PMID- 27352991 TI - Late mitral paravalvular leak. PMID- 27352992 TI - Plant adaptive radiation mediated by polyploid plasticity in transcriptomes. AB - The habitats of polyploid species are generally distinct from their parental species. Stebbins described polyploids as 'general purpose genotypes', which can tolerate a wide range of environmental conditions. However, little is known about its molecular basis because of the complexity of polyploid genomes. We hypothesized that allopolyploid species might utilize the expression patterns of both parents depending on environments (polyploid plasticity hypothesis). We focused on hydrological niche segregation along fine-scale soil moisture and waterlogging gradients. Two diploid species, Cardamine amara and Cardamine hirsuta, grew best in submerged and unsubmerged conditions, respectively, consistent with their natural habitats. Interestingly, the allotetraploid Cardamine flexuosa derived from them grew similarly in fluctuating as well as submerged and unsubmerged conditions, consistent with its wide environmental tolerance. A similar pattern was found in another species trio: allotetraploid Cardamine scutata and its parents. Using the close relatedness of Cardamine and Arabidopsis, we quantified genomewide expression patterns following dry and wet treatments using an Arabidopsis microarray. Hierarchical clustering analysis revealed that the expression pattern of C. flexuosa clustered with C. hirsuta in the dry condition and with C. amara in the wet condition, supporting our hypothesis. Furthermore, the induction levels of most genes in the allopolyploid were lower than in a specialist diploid species. This reflects a disadvantage of being allopolyploid arising from fixed heterozygosity. We propose that recurrent allopolyploid speciation along soil moisture and waterlogging gradients confers niche differentiation and reproductive isolation simultaneously and serves as a model for studying the molecular basis of ecological speciation and adaptive radiation. PMID- 27352993 TI - National attitudes towards mental health treatment: the importance of research evidence. AB - Most conceptualizations of evidence-based practice view it as a "three legged stool" consisting of: the use of best available research evidence, clinical expertise, and client preferences. Although empirical evidence and clinical expertise have received greater empirical attention, relatively little research has systematically explored client preferences. The present study analyzed self reported treatment preferences for various clinical and non-clinical presentations. Adult participants (n = 1262) residing in the United States were presented with diagnostic vignettes and rated their relative preferences among 5 treatment variables, including: use of an empirically supported treatment (EST), quality of the client-therapist relationship, therapist empathy, therapist experience, and client speaking for the majority of therapy sessions. Results indicated that participants endorsed significant preference for receiving an EST over other treatment variables for all clinical disorders, with effect sizes ranging from small to large depending on the diagnosis. There was slightly greater variability in treatment preferences for non-clinical issues, though participants generally reported greater preference for receiving an EST. Follow up questions provided further evidence for EST preferences. The implications of these results are discussed. PMID- 27352994 TI - CXCR4 antagonism overcomes diabetic stem cell mobilopathy. PMID- 27352995 TI - Photoluminescence, semiconductive properties and theoretical calculation of a novel bismuth biimidazole compound. AB - A novel bismuth biimidazole compound, [(BiCl4 )-(MU2 -Cl)2 -(BiCl4 )][(CH3 )4 2,2'-biimidazole]2 (1) with the (CH3 )4 -2,2'-biimidazole moiety generated in situ, was successfully prepared under hydrothermal conditions and structurally characterized using a single-crystal X-ray diffraction technique. Compound 1 is characteristic of an isolated structure, consisting of [(BiCl4 )-(MU2 -Cl)2 (BiCl4 )] and (CH3 )4 -2,2'-biimidazole moieties. Solid-state photoluminescence measurement reveals that it shows a strong emission in the blue region. Time dependent density functional theory studies show that this emission is ascribed to metal-to-ligand charge transfer. The solid-state diffuse reflectance spectrum reveals the existence of an optical band gap of 2.09 eV, indicating that it is a semiconductor. PMID- 27352996 TI - Short AntiMicrobial Peptides (SAMPs) as a class of extraordinary promising therapeutic agents. AB - The emergence of multidrug resistant bacteria has a direct impact on global public health because of the reduced potency of existing antibiotics against pathogens. Hence, there is a pressing need for new drugs with different modes of action that can kill microorganisms. Antimicrobial peptides (AMPs) can be regarded as an alternative tool for this purpose because they are proven to have therapeutic effects with broad-spectrum activities. There are some hurdles in using AMPs as clinical candidates such as toxicity, lack of stability and high budgets required for manufacturing. This can be overcome by developing shorter and more easily accessible AMPs, the so-called Short AntiMicrobial Peptides (SAMPs) that contain between two and ten amino acid residues. These are emerging as an attractive class of therapeutic agents with high potential for clinical use and possessing multifunctional activities. In this review we attempted to compile those SAMPs that have exhibited biological properties which are believed to hold promise for the future. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 27352997 TI - High-molecular-weight poly(Gly-Val-Gly-Val-Pro) synthesis through microwave irradiation. AB - In this study, we synthesized a polypeptide from its pentapeptide unit using microwave irradiation. Effective methods for polypeptide synthesis from unit peptides have not been reported. Here, we used a key elastin peptide, H GlyValGlyValPro-OH (GVGVP), as the monomer peptide. It is difficult to obtain poly(Gly-Val-Gly-Val-Pro) (poly(GVGVP)) from the pentapeptide unit of elastin, GVGVP, via polycondensation. Poly(GVGVP) prepared from genetically recombinant Escherichia coli is a well-known temperature-sensitive polypeptide, and this temperature sensitivity is known as the lower critical solution temperature. When microwave irradiation was performed in the presence of various additives, the pentapeptide (GVGVP) polycondensation reaction proceeded smoothly, resulting in a product with a high molecular weight in a relatively good yield. The reaction conditions, like microwave irradiation, coupling agents, and solvents, were optimized to increase the reaction efficiency. The product exhibited a molecular weight greater than Mr 7000. Further, the product could be synthesized on a gram scale. The synthesized polypeptide exhibited a temperature sensitivity that was similar to that of poly(GVGVP) prepared from genetically recombinant E. coli. Therefore, this technique offers a facile and quick approach to prepare polypeptides in large amounts. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 27352998 TI - Identification of a female spawn-associated Kazal-type inhibitor from the tropical abalone Haliotis asinina. AB - Abalone (Haliotis) undergoes a period of reproductive maturation, followed by the synchronous release of gametes, called broadcast spawning. Field and laboratory studies have shown that the tropical species Haliotis asinina undergoes a two week spawning cycle, thus providing an excellent opportunity to investigate the presence of endogenous spawning-associated peptides. In female H. asinina, we have isolated a peptide (5145 Da) whose relative abundance in hemolymph increases substantially just prior to spawning and is still detected using reverse-phase high-performance liquid chromatography chromatograms up to 1-day post-spawn. We have isolated this peptide from female hemolymph as well as samples prepared from the gravid female gonad, and demonstrated through comparative sequence analysis that it contains features characteristic of Kazal-type proteinase inhibitors (KPIs). Has-KPI is expressed specifically within the gonad of adult females. A recombinant Has-KPI was generated using a yeast expression system. The recombinant Has-KPI does not induce premature spawning of female H. asinina when administered intramuscularly. However it displays homomeric aggregations and interaction with at least one mollusc-type neuropeptide (LRDFVamide), suggesting a role for it in regulating neuropeptide endocrine communication. This research provides new understanding of a peptide that can regulate reproductive processes in female abalone, which has the potential to lead to the development of greater control over abalone spawning. The findings also highlight the need to further explore abalone reproduction to clearly define a role for novel spawning associated peptide in sexual maturation and spawning. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 27352999 TI - Elastography in Dermatology. AB - Elastography is a recently developed ultrasound technique applicable to various medical specialties. It provides information on the physical properties of tissues in the context of physiologic and pathologic alterations. In this review we explain the physical principles of the method, the information provided by the different elastography techniques, and its new applications in clinical dermatology. PMID- 27353000 TI - Cargo binding promotes KDEL receptor clustering at the mammalian cell surface. AB - Transmembrane receptor clustering is a ubiquitous phenomenon in pro- and eukaryotic cells to physically sense receptor/ligand interactions and subsequently translate an exogenous signal into a cellular response. Despite that receptor cluster formation has been described for a wide variety of receptors, ranging from chemotactic receptors in bacteria to growth factor and neurotransmitter receptors in mammalian cells, a mechanistic understanding of the underlying molecular processes is still puzzling. In an attempt to fill this gap we followed a combined experimental and theoretical approach by dissecting and modulating cargo binding, internalization and cellular response mediated by KDEL receptors (KDELRs) at the mammalian cell surface after interaction with a model cargo/ligand. Using a fluorescent variant of ricin toxin A chain as KDELR-ligand (eGFP-RTA(H/KDEL)), we demonstrate that cargo binding induces dose-dependent receptor cluster formation at and subsequent internalization from the membrane which is associated and counteracted by anterograde and microtubule-assisted receptor transport to preferred docking sites at the plasma membrane. By means of analytical arguments and extensive numerical simulations we show that cargo synchronized receptor transport from and to the membrane is causative for KDELR/cargo cluster formation at the mammalian cell surface. PMID- 27353002 TI - Finite particle size drives defect-mediated domain structures in strongly confined colloidal liquid crystals. AB - When liquid crystals are confined to finite volumes, the competition between the surface anchoring imposed by the boundaries and the intrinsic orientational symmetry-breaking of these materials gives rise to a host of intriguing phenomena involving topological defect structures. For synthetic molecular mesogens, like the ones used in liquid-crystal displays, these defect structures are independent of the size of the molecules and well described by continuum theories. In contrast, colloidal systems such as carbon nanotubes and biopolymers have micron sized lengths, so continuum descriptions are expected to break down under strong confinement conditions. Here, we show, by a combination of computer simulations and experiments with virus particles in tailor-made disk- and annulus-shaped microchambers, that strong confinement of colloidal liquid crystals leads to novel defect-stabilized symmetrical domain structures. These finite-size effects point to a potential for designing optically active microstructures, exploiting the as yet unexplored regime of highly confined liquid crystals. PMID- 27353001 TI - Altered expression of mir-222 and mir-25 influences diverse gene expression changes in transformed normal and anaplastic thyroid cells, and impacts on MEK and TRAIL protein expression. AB - Thyroid cancer is the most common endocrine malignancy and accounts for the majority of endocrine cancer-related deaths each year. Our group and others have previously demonstrated dysfunctional microRNA (miRNA or miR) expression in the context of thyroid cancer. The objective of the present study was to investigate the impact of synthetic manipulation of expression of miR-25 and miR-222 in benign and malignant thyroid cells. miR-25 and miR-222 expression was upregulated in 8505C (an anaplastic thyroid cell line) and Nthy-ori (a SV40-immortalised thyroid cell line) cells, respectively. A transcriptomics-based approach was utilised to identify targets of the two miRNAs and real-time PCR and western blotting were used to validate a subset of the targets. Almost 100 mRNAs of diverse functions were found to be either directly or indirectly targeted by both miR-222 and miR-25 [fold change >=2, false discovery rate (FDR) <=0.05]. Gene ontology analysis showed the miR-25 gene target list to be significantly enriched for genes involved in cell adhesion. Fluidigm real-time PCR technologies were used to validate the downregulation of 23 and 22 genes in response to miR-25 and miR-222 overexpression, respectively. The reduction of the expression of two miR 25 protein targets, TNF-related apoptosis-inducing ligand (TRAIL) and mitogen activated protein kinase kinase 4 (MEK4), was also validated. Manipulating the expression of both miR-222 and miR-25 influenced diverse gene expression changes in thyroid cells. Increased expression of miR-25 reduced MEK4 and TRAIL protein expression, and cell adhesion and apoptosis are important aspects of miR-25 functioning in thyroid cells. PMID- 27353003 TI - Supramolecular core-shell nanoparticles for photoconductive device applications. AB - We report a breakthrough discovery involving supramolecular-based strategies to construct novel core-shell heterojunction nanoparticles with hydrophilic adenine functionalized polythiophene (PAT) as the core and hydrophobic phenyl-C61-butyric acid methyl ester (PCBM) as the shell, which enables the conception of new functional supramolecular assemblies for constructing functional nanomaterials for applications in optoelectronic devices. The generated nanoparticles exhibit uniform spherical shape, well-controlled tuning of particle size with narrow size distributions, and excellent electrochemical stability in solution and the solid state owing to highly efficient energy transfer from PAT to PCBM. When the PAT/PCBM nanoparticles were fabricated into a photoconducting layer in an electronic device, the resulting device showed excellent electric conduction characteristics, including an electrically-tunable voltage-controlled switch, and high short-circuit current and open-circuit voltage. These observations demonstrate how the self-assembly of PAT/PCBM into specific nanostructures may help to promote efficient charge generation and transport processes, suggesting potential for a wide variety of applications as a promising candidate material for bulk heterojunction polymer devices. PMID- 27353004 TI - Peptide hormones regulate the physiological functions of reproductive organs in Tenebrio molitor males. AB - In insects, the majority of studies have been conducted on the hormonal regulation of female reproduction. Thus far, little is known about the regulation of male reproductive physiology, especially by peptide hormones. We report here, for the first time in insects, the effects of three peptides, Neb-colloostatin (SIVPLGLPVPIGPIVVGPR), Neb-TMOF (NPTNLH) and Lepde-NPF-I (ARGPQLRLRFa), on various aspects of reproduction in male Tenebrio molitor beetles. All three tested peptides increased the soluble protein concentration in the testes and the dry mass of the beetle's testes. They also significantly changed the protein profiles of the testes. Injection of these peptides also significantly changed the number of sperm cells in the testes. However, the observed effects were age specific. The most prominent changes were observed in 4-day-old males. Neb colloostatin and Neb-TMOF decreased the number of sperm cells, whereas Lepde-NPF I increased the number of spermatocytes. Moreover, in vitro experiments revealed that Neb-TMOF and Lepde-NPF-I increased the contractility of the ejaculatory duct of T. molitor males. The results obtained suggest that different reproductive processes in males might be regulated by complex mechanisms. PMID- 27353005 TI - Stress-associated radiation effects in pygmy wood mouse Apodemus uralensis (Muridae, Rodentia) populations from the East-Urals Radioactive Trace. AB - This work is based on the comparative analysis of data obtained in the course of monitoring pygmy wood mouse populations (Apodemus uralensis Pallas, 1811) in the East-Urals Radioactive Trace (EURT) area and background territories. The effect of population size and its interaction with the radioactivity on biochemical parameters in the spleen and adrenal glands was studied. The concentrations of total lipids, proteins, DNA and RNA, activity of glucose-6-phosphate isomerase and catalase as well as the level of lipid peroxidation (LPO) were evaluated. The functional-metabolic shifts seen with large population sizes were characterized by delipidisation of adrenocortical cells, increased LPO as the main mechanism for steroidogenesis, growth of the protein components of the adrenal glands to maintain their hyperfunction, as well as immunosuppression associated with the restriction of carbohydrates providing splenocytes, reduction of DNA synthesis, and the development of a pro-/antioxidant imbalance. Reactivity of the neuroendocrine and hematopoietic systems of animals experiencing a high population density was higher in the EURT zone compared with the reference group. This difference can be explained by the additional stress from the chronic radiation exposure. The level of LPO, catalase activity, and DNA/protein ratio in the spleen and the total protein content in the adrenal glands were the most sensitive to the interaction of population size and radiation exposure. The harmful effect (distress) of the interaction of non-radiation and radiation factors can manifest when there is a population abundance above 30 ind./100 trap day and a radiation burden which exceeds the lower boundary of the Derived Consideration Reference Levels, which is above 0.1 mGy/day. PMID- 27353006 TI - Surface metabolites of the brown alga Taonia atomaria have the ability to regulate epibiosis. AB - This study aimed to improve understanding of the strategies developed by the Mediterranean seaweed Taonia atomaria to chemically control bacterial epibiosis. An experimental protocol was optimized to specifically extract algal surface associated metabolites by a technique involving dipping in organic solvents whilst the integrity of algal cell membranes was assessed by fluorescent microscopy. This methodology was validated using mass spectrometry-based profiles of algal extracts and analysis of their principal components, which led to the selection of methanol as the extraction solvent with a maximum exposure time of 15 s. Six compounds (A-F) were identified in the resulting surface extracts. Two of these surface-associated compounds (B and C) showed selective anti-adhesion properties against reference bacterial strains isolated from artificial surfaces while remaining inactive against epibiotic bacteria of T. atomaria. Such specificity was not observed for commercial antifouling biocides and other molecules identified in the surface or whole-cell extracts of T. atomaria. PMID- 27353007 TI - Carbon nanotubes dispersed in aqueous solution by ruthenium(ii) polypyridyl complexes. AB - Cationic ruthenium(ii) polypyridyl complexes with appended pyrene groups have been synthesized and used to disperse single-walled carbon nanotubes (SWCNT) in aqueous solutions. To this end, planar pyrene groups enable association by means of pi-stacking onto carbon nanotubes and, in turn, the attachment of the cationic ruthenium complexes. Importantly, the ionic nature of the ruthenium complexes allows the formation of stable dispersions featuring individualized SWCNTs in water as confirmed in a number of spectroscopic and microscopic assays. In addition, steady-state photoluminescence spectroscopy was used to probe the excited state interactions between the ruthenium complexes and SWCNTs. These studies show that the photoluminescence of both, that is, of the ruthenium complexes and of SWCNTs, are quenched when they interact with each other. Pump probe transient absorption experiments were performed to shed light onto the nature of the photoluminescence quenching, showing carbon nanotube-based bands with picosecond lifetimes, but no new bands which could be unambigously assigned to photoinduced charge transfer process. Thus, from the spectroscopic data, we conclude that quenching of the photoluminescence of the ruthenium complexes is due to energy transfer to proximal SWCNTs. PMID- 27353008 TI - Elevated 12-hydroxyeicosatetraenoic acid (12-HETE) levels in serum of individuals with newly diagnosed Type 1 diabetes. PMID- 27353009 TI - Editorial Comment to Risk factors of systemic inflammation response syndrome after endoscopic combined intrarenal surgery in the modified Valdivia position. PMID- 27353010 TI - A world-wide survey and field study in clinical haemostasis laboratories to evaluate FVIII:C activity assay variability of ADYNOVATE and OBIZUR in comparison with ADVATE. AB - INTRODUCTION: Discrepancies have been previously reported for one-stage clotting and chromogenic assays for FVIII activity analysis. Inter-laboratory variations in instruments, method of clot detection, assay set-up, reference standard calibration, reagent source and reagent composition all contribute to assay variability. AIM: To characterise multilaboratory assay variability in measuring ADYNOVATE, OBIZUR and ADVATE FVIII activity in human plasma and survey multinational FVIII activity assay preferences. METHODS: As samples from patients treated with either of the FVIII products are not available in the quantities required for a systematic collaborative study, haemophilia A plasma was spiked in vitro with either ADYNOVATE (PEGylated rFVIII), OBIZUR [Porcine Sequence Antihaemophilic Factor (Recombinant)] or ADVATE at high (0.80 IU or U mL-1 ), medium (0.20 IU or U mL-1 ) and low (0.05 IU or U mL-1 ) FVIII concentrations, based on labelled potencies. Clinical laboratories used their routine FVIII activity assay to determine FVIII activity of each product. Thirty-five data sets using one-stage clotting assay and 11 sets using chromogenic assay were obtained. RESULTS: A vast majority of laboratories (98%) prefer and rely on the one-stage clotting assay. Mean recoveries across all concentrations were 113%, 120% and 127% for ADYNOVATE, OBIZUR and ADVATE respectively. Assay variation was comparable between ADVATE, ADYNOVATE and OBIZUR with inter-laboratory percent coefficients of variation (%CV) ranging from 11 to 22%. Mean chromogenic assay results were 116%, 51% and 113% for ADYNOVATE, OBIZUR and ADVATE respectively. Inter-laboratory CV's were similar for ADYNOVATE, OBIZUR and ADVATE. CONCLUSIONS: One-stage clotting assays can and will be used with sufficient accuracy and precision for the measurement of ADYNOVATE, OBIZUR and ADVATE in plasma samples from subjects with haemophilia A. Chromogenic assay underestimates OBIZUR potency, particularly at lower concentrations. PMID- 27353011 TI - Binding and thermodynamics of REV peptide-ctDNA interaction. AB - The thermodynamics of DNA-ligand binding is important as it provides useful information to understand the details of binding processes. HIV-1 REV response element (RRE) located in the env coding region of the viral genome is reported to be well conserved across different HIV-1 isolates. In this study, the binding characteristics of Calf thymus DNA (ctDNA) and REV peptide from HIV-1 were investigated using spectroscopic (UV-visible, fluorescence, and circular dichroism (CD)) and isothermal titration calorimetric (ITC) techniques. Thermal stability and ligand binding properties of the ctDNA revealed that native ctDNA had a Tm of 75.5 degrees C, whereas the ctDNA-REV peptide complex exhibited an incremental shift in the Tm by 8 degrees C, indicating thermal stability of the complex. CD data indicated increased ellipticity due to large conformational changes in ctDNA molecule upon binding with REV peptide and two binding stoichiometric modes are apparent. The ctDNA experienced condensation due to large conformational changes in the presence of REV peptide and positive B->Psi transition was observed at higher molar charge ratios. Fluorescence studies performed at several ligand concentrations revealed a gradual decrease in the fluorescence intensity of EtBr-bound ctDNA in response to increasing ligand concentrations. The fluorescence data further confirmed two stoichiometric modes of binding for ctDNA-REV peptide complex as previously observed with CD studies. The binding enthalpies were determined using ITC in the temperature range of 293 K-308 K. The ITC binding isotherm was exothermic at all temperatures examined, with low DeltaH values indicating that the ctDNA-REV peptide interaction is driven largely by entropy. The heat capacity change (DeltaCp ) was insignificant, an unusual finding in the area of DNA-peptide interaction studies. The variation in the values obtained for DeltaH, DeltaS, and DeltaG with temperature further suggests that ctDNA-REV peptide interaction is entropically driven. ITC based analysis of salt dependence of binding constant gave a charge value (Z) = +4.01, as determined for the deltalnK/deltaln[Na+ ] parameter, suggesting the participation of only 3-4 Arg out of 11 Arg charge from REV peptide. The stoichiometry observed for the complex was three molar charge of REV peptide binding per molar charge of ctDNA. ITC based analysis further confirmed that the binding between ctDNA and REV peptide is governed by electrostatic interaction. Molecular interactions including H-bonding, van der Waals forces, and solvent molecules rearrangement, underlie the binding of REV peptide to ctDNA. PMID- 27353012 TI - Approach To Deliver Two Antioxidant Enzymes with Mesoporous Silica Nanoparticles into Cells. AB - Reactive oxygen species (ROS) are important factors in many clinical diseases. However, direct delivery of antioxidant enzymes into cells is difficult due to poor cell uptake. A proper design of delivery of enzymes by nanoparticles is very desirable for therapeutic purposes. To overcome the cell barrier problem, a designed mesoporous silica nanoparticle (MSN) system with attached TAT-fusion denatured enzyme for enhancing cell membrane penetration has been developed. Simultaneous delivery of two up-downstream antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase(GPx), reveals synergistic efficiency of ROS scavenging, compared to single antioxidant enzyme delivery. TAT peptide conjugation provided a facile nonendocytosis cell uptake and escape from endosome while moving and aggregating along the cytoskeleton that would allow them to be close to each other at the same time, resulting in the cellular antioxidation cascade reaction. The two-enzyme delivery shows a significant synergistic effect for protecting cells against ROS-induced cell damage and cell cycle arrest. The nanocarrier strategy for enzyme delivery demonstrates that intracellular anti-ROS cascade reactions could be regulated by multifunctional MSNs carrying image fluorophore and relevant antioxidation enzymes. PMID- 27353013 TI - A cross-sectional investigation of public attitudes toward dementia in Bristol and South Gloucestershire using the approaches to dementia questionnaire. AB - BACKGROUND: To date, surveys of attitudes toward dementia have largely been conducted using unvalidated materials or have focused on healthcare professionals supporting people affected by dementia. The aim of this study was to carry out a survey of public attitudes toward people affected by dementia in Bristol and South Gloucestershire. METHODS: A survey was carried out using a modified version of the Approaches to Dementia Questionnaire (ADQ). Data from people living outside the area, and people who were working with people affected by dementia were omitted from the analysis. Responses from the remaining 794 ADQ questionnaires were weighted to correct for under-represented age, gender, and ethnic groups. RESULTS: Younger people held more positive attitudes toward dementia than older people. Individuals who identified themselves as White held more positive attitudes than non-White individuals. Individuals with personal experience of dementia held more positive attitudes than those with no experience of dementia. When considering age differences, gender played a role, with younger men having more positive scores than other groups. CONCLUSIONS: This is one of the first surveys of public attitudes to dementia to use a validated questionnaire such as the ADQ. The study provides a baseline of attitudes toward dementia for the Bristol and South Gloucestershire areas, against which we will be able to compare changes over time. This is important due to the emphasis in public health campaigns on improving attitudes toward dementia. PMID- 27353014 TI - Lotka systems with directed dispersal dynamics: Competition and influence of diffusion strategies. AB - We study a Lotka system describing two competing populations, and each of them chooses its diffusion strategy as the tendency to have a distribution proportional to a certain positive prescribed function. For instance, the standard diffusion corresponds to the choice of a uniform distribution. The paper is focused on the interplay of species competition and diffusion strategies. In the case when one of the diffusion strategies is proportional to the carrying capacity, while the other is not, and the competition does not discriminate the former species, we prove the competitive exclusion of the latter one. If the competition favors the latter species, there is still a range of parameters for which there is a coexistence, thanks to the better dispersal strategy chosen by the former species. The dependency on the interaction type, diffusion coefficients and intrinsic growth rates is explored. We prove that in the limit case, higher diffusion coefficients are detrimental while higher growth rates, as well as lower resources sharing, are beneficial for population survival. PMID- 27353016 TI - Corrigendum to "Reasons for premature termination of dialectical behavior therapy for inpatients with borderline personality disorder". PMID- 27353015 TI - Genome-wide characterization of the beta-1,3-glucanase gene family in Gossypium by comparative analysis. AB - The beta-1,3-glucanase gene family is involved in a wide range of plant developmental processes as well as pathogen defense mechanisms. Comprehensive analyses of beta-1,3-glucanase genes (GLUs) have not been reported in cotton. Here, we identified 67, 68, 130 and 158 GLUs in four sequenced cotton species, G. raimondii (D5), G. arboreum (A2), G. hirsutum acc. TM-1 (AD1), and G. barbadense acc. 3-79 (AD2), respectively. Cotton GLUs can be classified into the eight subfamilies (A-H), and their protein domain architecture and intron/exon structure are relatively conserved within each subfamily. Sixty-seven GLUs in G. raimondii were anchored onto 13 chromosomes, with 27 genes involved in segmental duplications, and 13 in tandem duplications. Expression patterns showed highly developmental and spatial regulation of GLUs in TM-1. In particular, the expression of individual member of GLUs in subfamily E was limited to roots, leaves, floral organs or fibers. Members of subfamily E also showed more protein evolution and subgenome expression bias compared with members of other subfamilies. We clarified that GLU42 and GLU43 in subfamily E were preferentially expressed in root and leaf tissues and significantly upregulated after Verticillium dahliae inoculation. Silencing of GLU42 and GLU43 significantly increased the susceptibility of cotton to V. dahliae. PMID- 27353017 TI - Corrigendum to "A randomized controlled trial evaluating a parenting program designed specifically for grandparents". PMID- 27353018 TI - Comparison of two high-resolution manometry software systems in evaluating esophageal motor function. AB - BACKGROUND: High-resolution manometry (HRM) utilizes software tools to diagnose esophageal motor disorders. Performance of these software metrics could be affected by averaging and by software characteristics of different manufacturers. METHODS: High-resolution manometry studies on 86 patients referred for antireflux surgery (61.6 +/- 1.4 year, 70% F) and 20 healthy controls (27.9 +/- 0.7 year, 45% F) were first subject to standard analysis (Medtronic, Duluth, GA, USA). Coordinates for each of 10 test swallows were exported and averaged to generate a composite swallow. The swallows and averaged composites were imported as ASCII file format into Manoview (Medtronic) and Medical Measurement Systems database reporter (MMS, Dover, NH, USA), and analyses repeated. Comparisons were made between standard and composite swallow interpretations. KEY RESULTS: Correlation between the two systems was high for mean distal contractile integral (DCI, r2 >= 0.9) but lower for integrated relaxation pressure (IRP, r2 = 0.7). Excluding achalasia, six patients with outflow obstruction (mean IRP 23.2 +/- 2.1 with 10 swallow average) were identified by both systems. An additional nine patients (10.5%) were identified as outflow obstruction (15 mmHg threshold) with MMS 10 swallow and four with MMS composite swallow evaluation; only one was confirmed. Ineffective esophageal motility was diagnosed by 10-swallow evaluation in 19 (22.1%) with Manoview, and 20 (23.3%) with MMS. On Manoview composite, 17 had DCI <450 mmHg/cm/s, and on MMS composite, 21, (p >= 0.85 for each comparison) but these did not impact diagnostic conclusions. CONCLUSIONS & INFERENCES: Comparison of 10 swallow and composite swallows demonstrate variability in software metrics between manometry systems. Our data support use of manufacturer specific software metrics on 10-swallow sequences. PMID- 27353019 TI - Non-canonical NFkappaB activation promotes chemokine expression in podocytes. AB - TNF-like weak inducer of apoptosis (TWEAK) receptor Fn14 is expressed by podocytes and Fn14 deficiency protects from experimental proteinuric kidney disease. However, the downstream effectors of TWEAK/Fn14 in podocytes are poorly characterized. We have explored TWEAK activation of non-canonical NFkappaB signaling in cultured podocytes. In cultured podocytes, TWEAK increased the expression of the chemokines CCL21, CCL19 and RANTES in a time-dependent manner. The inhibitor of canonical NFkappaB activation parthenolide inhibited the CCL19 and the early RANTES responses, but not the CCL21 or late RANTES responses. In this regard, TWEAK induced non-canonical NFkappaB activation in podocytes, characterized by NFkappaB2/p100 processing to NFkappaB2/p52 and nuclear migration of RelB/p52. Silencing by a specific siRNA of NIK, the upstream kinase of the non canonical NFkappaB pathway, prevented CCL21 upregulation but did not modulate CCL19 or RANTES expression in response to TWEAK, thus establishing CCL21 as a non canonical NFkappaB target in podocytes. Increased kidney Fn14 and CCL21 expression was also observed in rat proteinuric kidney disease induced by puromycin, and was localized to podocytes. In conclusion, TWEAK activates the non canonical NFkappaB pathway in podocytes, leading to upregulation of CCL21 expression. The non-canonical NFkappaB pathway should be explored as a potential therapeutic target in proteinuric kidney disease. PMID- 27353020 TI - Invalidation of Diphyllobothrium hottai (Cestoda: Diphyllobothriidae) based on morphological and molecular phylogenetic analyses. AB - Diphyllobothrium hottai Yazaki, Fukumoto & Abe, 1988 was described based on the morphology of adult worms recovered from golden hamsters that had been experimentally infected with plerocercoids obtained from Japanese surf smelts (Hypomesus pretiosus japonicus) and olive rainbow smelts (Osmerus eperlanus mordax). Although D. hottai was considered to be distinct from Diphyllobothrium ditremum (Creplin, 1825), their taxonomic relationship requires further clarification. In our study, D. hottai and D. ditremum obtained from hamsters experimentally infected with plerocercoids isolated from Japanese surf smelts were compared using morphological and molecular methods. The criterion usually used to differentiate between D. hottai and D. ditremum is the difference in the angle between the long axis of the cirrus sac and that of the seminal vesicle. However, we found variation of the angle within the same individual and, one specimen showed both of the different angles that were supposedly unique to each of the species. Furthermore, phylogenetic analysis of the complete sequences of the mitochondrial cytochrome c oxidase subunit 1 and cytochrome b genes revealed that both species were genetically indistinguishable. Therefore, D. hottai is considered to be a junior synonym of D. ditremum. PMID- 27353021 TI - Taxonomic status of Syngamus nematodes parasitizing passeriform hosts from Central Europe: Morphological, morphometric and molecular identification. AB - The systematic position and validity of species within genus Syngamus have always been controversial. In this present work, we evaluated the taxonomic status and phylogenetic relationships between three species of Syngamus nematodes (Syngamus trachea, Syngamus taiga and Syngamus merulae) and one taxa, determined only to the generic level, collected from respiratory tracts of passeriform hosts from Central Europe using newly obtained sequences of 2 nuclear markers (internal transcribed spacers 1 and 2 [ITS1, ITS2]) and a fragment of mitochondrial cytochrome oxidase I [COI] gene. Our results clearly showed that S. trachea, S. taiga and S. merulae are valid, molecularly and morphologically distinct species. Moreover, molecular analysis of adult female of Syngamus sp. collected from tracheae of the European robin Erithacus rubecula clearly indicate that these comprise separate species. In the derived phylogeny, the Syngamus clade is divided into two sub-clades: one comprised Syngamus species with a characteristic, well-developed cuticular collar around the oral opening (S. trachea and S. taiga) and a second that groups taxa without or with rudimentary collar (S. merulae and currently sequenced Syngamus sp. from Erithacus rubecula). These results clearly suggest that the degree of collar development (well developed vs. rudimentary/absent) may be an important phylogenetic feature for determining the structure of the genus Syngamus on subgeneric level. Additionally, our results support historical division of the genus Syngamus into two subgenera S. (Syngamus) and S. (Ornithogamus). PMID- 27353022 TI - Serial use of pentamidine and miltefosine for treating Leishmania infantum-HIV coinfection. AB - Liposomal amphotericin B (LAmb) may fail to heal Leishmania infantum visceral leishmaniasis (VL) in the immunodeficient host. There are currently no guidelines on how to treat such patients and efficacy of miltefosine monotherapy seems limited in this indication. We present 2 cases of patients with VL and AIDS for which LAmb had to be interrupted (one because of toxicity, one because of treatment failure) and who were treated effectively with pentamidine followed by miltefosine. PMID- 27353023 TI - Asthma associated with chronic rhinosinusitis: a population-based study. AB - BACKGROUND: Few studies have investigated the relationship between asthma and chronic rhinosinusitis (CRS). The present study investigated the association between asthma and the risk of CRS in a large national sample. METHODS: Patients newly diagnosed with asthma (International Classification of Diseases, Ninth Revision [ICD-9], Clinical Modification code 493) between 2000 and 2008 were identified from the Taiwan National Health Insurance Research Database. The cases were compared with sex-, age-, residence-, and insurance premium-matched controls, and both groups were followed until the end of 2009 for incidences of CRS with or without nasal polyps (CRSwNP or CRSsNP, respectively). Competing risk adjusted Cox regression analyses were performed after adjustment for sex, age, residence, insurance premium, steroid use, hyperlipidemia, diabetes, hypertension, coronary artery disease, Charlson comorbidity index score, and mortality. We also performed a case-control study to determine the association between asthma and CRS. RESULTS: The cohort study analysis examined 81,462 patients with a mean +/- standard deviation (SD) follow-up period of 5.8 +/- 2.4 years. Asthma was an independent predictor of CRSsNP (hazard ratio = 2.58; 95% confidence interval [CI], 2.20 to 3.03; p < 0.001) in the fully adjusted models. In the case-control analysis, both CRSwNP and CRSsNP were associated with asthma in the fully adjusted models. CONCLUSION: Asthma was associated with increased risks of CRSwNP and CRSsNP, independent of several potential confounding factors. PMID- 27353024 TI - Medical ultrasound diagnosis in the near future as we move toward the era of the singularity. PMID- 27353025 TI - Developing and pilot testing an electronic medical record-based allergen immunotherapy template. PMID- 27353026 TI - A functional neuregulin-1 gene variant and stressful life events: Effect on drug use in a longitudinal population-representative cohort study. AB - BACKGROUND: The neuregulin 1 gene is a susceptibility gene for substance dependence. A functional polymorphism (SNP8NRG243177/rs6994992; C/T) in the promoter region of the brain-specific type IV neuregulin-1 gene ( NRG1) has been associated with psychiatric disorders (e.g. schizophrenia and bipolar disorder) that often present higher odds of smoking, alcohol and illicit drug use. This study assessed the association of the NRG1 genotype with drug use and possible interaction with stressful life events (SLEs). METHODS: The database of the Estonian Children Personality Behaviour and Health Study (beginning in 1998) was used. Cohorts of children initially 9 years old ( n=583; followed up at 15 and 18 years) and 15 years old ( n=593; followed up at 18 and 25 years) provided self reports on alcohol, tobacco and illicit substance use and SLEs. Psychiatric assessment based on DSM-IV was carried out on the older birth cohort at age 25 to assess the lifetime presence of substance use disorders. NRG1 rs6994992 was genotyped in all participants by TaqMan(r) Pre-Designed SNP Genotyping Assay on the Applied Biosystems ViiATM 7 Real-Time PCR System. The minor (T) allele frequency was 0.37. RESULTS: NRG1 rs6994992 C/C homozygotes, especially those who had experienced more SLEs, were more likely to develop alcohol use disorders by young adulthood, were generally more active consumers of tobacco products, and had more likely used illicit drugs. In T allele carriers, SLEs had a negligible effect on substance use. CONCLUSIONS: In humans, NRG1 genotype is associated with substance use, and this relationship is moderated by adverse life events, with a gain-of-function allele being protective. PMID- 27353027 TI - The good and bad news about glutamate in drug addiction. AB - In 1998 we published a perspective review describing how drug-induced neuroadaptations might serve towards understanding drug craving. We proposed experimental perspectives to help discern data relevant to long-lasting brain changes, and to distinguish dopamine-related changes that were largely pharmacological from glutamatergic changes that were based on drug-environment associations. These perspectives are embedded in drug abuse research, and the last 18 years has witnessed marked development in understanding addiction associated corticostriatal glutamate plasticity. Here we propose three new perspectives on how the field might approach integrating and using the emerging data on glutamatergic adaptations. (1) Consider adaptations produced in kind across drug classes as most useful towards understanding shared characteristics of addiction, such as relapse. (2) Consider how drug-induced changes in glia and the extracellular matrix may contribute to synaptic alterations. (3) Make measurements not only at late withdrawal, but also during drug seeking events to capture transient changes that mediate active drug seeking that are shared across drug classes. PMID- 27353028 TI - Distinct Transcriptional Changes and Epithelial-Stromal Interactions Are Altered in Early-Stage Colon Cancer Development. AB - Although the progression of mutated colonic cells is dependent upon interactions between the initiated epithelium and surrounding stroma, the nature of these interactions is poorly understood. Here, the development of an ultrasensitive laser capture microdissection (LCM)/RNA-seq approach for studying the epithelial and stromal compartments of aberrant crypt foci (ACF) is described. ACF are the earliest identifiable preneoplastic lesion found within the human colon and are detected using high-definition endoscopy with contrast dye spray. The current analysis focused on the epithelium of ACF with somatic mutations to either KRAS, BRAF, or APC, and expression patterns compared with normal mucosa from each patient. By comparing gene expression patterns among groups, an increase in a number of proinflammatory NF-kappaB target genes was identified that was specific to ACF epithelium, including TIMP1, RELA, and RELB Distinct transcriptional changes associated with each somatic mutation were observed and a subset of ACF display BRAF(V600E)-mediated senescence-associated transcriptome characterized by increased expression of CDKN2A Finally, LCM-captured ACF-associated stroma was found to be transcriptionally distinct from normal-appearing stroma, with an upregulation of genes related to immune cell infiltration and fibroblast activation. Immunofluorescence confirmed increased CD3(+) T cells within the stromal microenvironment of ACF and an abundance of activated fibroblasts. Collectively, these results provide new insight into the cellular interplay that occurs at the earliest stages of colonic neoplasia, highlighting the important role of NF-kappaB, activated stromal fibroblasts, and lymphocyte infiltration. IMPLICATIONS: Fibroblasts and immune cells in the stromal microenvironment play an important role during the earliest stages of colon carcinogenesis. Mol Cancer Res; 14(9); 795-804. (c)2016 AACR. PMID- 27353029 TI - Notch Signaling Activation Is Associated with Patient Mortality and Increased FGF1-Mediated Invasion in Squamous Cell Carcinoma of the Oral Cavity. AB - Oral squamous cell carcinoma (OSCC) is a cancer subtype that lacks validated prognostic and therapeutic biomarkers, and human papillomavirus status has not proven beneficial in predicting patient outcomes. A gene expression pathway analysis was conducted using OSCC patient specimens to identify molecular targets that may improve management of this disease. RNA was isolated from 19 OSCCs treated surgically at the University of Alabama at Birmingham (UAB; Birmingham, AL) and evaluated using the NanoString nCounter system. Results were confirmed using the oral cavity subdivision of the Head and Neck Squamous Cell Carcinoma Cancer (HNSCC) study generated by The Cancer Genome Atlas (TCGA) Research Network. Further characterization of the in vitro phenotype produced by Notch pathway activation in HNSCC cell lines included gene expression, proliferation, cell cycle, migration, invasion, and radiosensitivity. In both UAB and TCGA samples, Notch pathway upregulation was significantly correlated with patient mortality status and with expression of the proinvasive gene FGF1 In vitro Notch activation in HNSCC cells increased transcription of FGF1 and induced a marked increase in cell migration and invasion, which was fully abrogated by FGF1 knockdown. These results reveal that increased Notch pathway signaling plays a role in cancer progression and patient outcomes in OSCC. Accordingly, the Notch FGF interaction should be further studied as a prognostic biomarker and potential therapeutic target for OSCC. IMPLICATIONS: Patients with squamous cell carcinoma of the oral cavity who succumb to their disease are more likely to have upregulated Notch signaling, which may mediate a more invasive phenotype through increased FGF1 transcription. Mol Cancer Res; 14(9); 883-91. (c)2016 AACR. PMID- 27353030 TI - Changing models of care for emergency surgical and trauma patients in Singapore. AB - The last 15 years have seen changing patterns of injury in emergency surgery and trauma patients. The ability to diagnose, treat and manage these patients nonoperatively has led to a decline in interest in trauma surgery as a career. In addition, healthcare systems face multiple challenges, including limited resources, an ageing population and increasing subspecialisation of medical care, while maintaining government-directed standards and managing public expectations. In the West, these challenges have led to the emergence of a new subspecialty, 'acute care surgery', with some models of care providing dedicated acute surgical units or separating acute and elective streams with the existing manpower resources. The outcomes for emergency surgery patients and efficiency gains are promising. In Singapore, Khoo Teck Puat Hospital has implemented its first dedicated acute surgical unit. This article outlines the evolution of acute care surgery and its relevance to Asia. PMID- 27353031 TI - Drinking Patterns Among Older Couples: Longitudinal Associations With Negative Marital Quality. AB - Objectives: Research with younger couples indicates that alcohol use has powerful effects on marital quality, but less work has examined the effects of drinking among older couples. This study examined whether dyadic patterns of drinking status among older couples are associated with negative marital quality over time. Method: Married participants (N = 4864) from the Health and Retirement Study reported on alcohol consumption (whether they drink alcohol and average amount consumed per week) and negative marital quality (e.g., criticism and demands) across two waves (Wave 1 2006/2008 and Wave 2 2010/2012). Results: Concordant drinking couples reported decreased negative marital quality over time, and these links were significantly greater among wives. Wives who reported drinking alcohol reported decreased negative marital quality over time when husbands also reported drinking and increased negative marital quality over time when husbands reported not drinking. Discussion: The present findings stress the importance of considering the drinking status rather than the amount of alcohol consumed of both members of the couple when attempting to understand drinking and marital quality among older couples. These findings are particularly salient given the increased drinking among baby boomers and the importance of marital quality for health among older couples. PMID- 27353032 TI - Enlarged colitogenic T cell population paradoxically supports colitis prevention through the B-lymphocyte-dependent peripheral generation of CD4(+)Foxp3(+) Treg cells. AB - Intestinal inflammation can be induced by the reconstitution of T/B cell deficient mice with low numbers of CD4(+) T lymphocytes depleted of CD25(+)Foxp3(+) regulatory T cells (Treg). Using RAG-knockout mice as recipients of either splenocytes exclusively depleted of CD25(+) cells or FACS-purified CD4(+)CD25(-)Foxp3(-) T cells, we found that the augmentation of potentially colitogenic naive T cell numbers in the inoculum was unexpectedly beneficial for the suppression of colon disease and maintenance of immune homeostasis. Protection against T cell-mediated colitis correlated with a significant increment in the frequency of peripherally-induced CD4(+)CD25(+)Foxp3(+) T (pTreg) cells, especially in the mesenteric lymph nodes, an effect that required the presence of B cells and CD4(+)CD25(-)Foxp3(+) cells in physiological proportions. Our findings support a model whereby the interplay between B lymphocytes and a diversified naive T cell repertoire is critical for the generation of CD4(+)CD25(+)Foxp3(+) pTreg cells and colitis suppression. PMID- 27353033 TI - Erratum to: The effect of soluble E-selectin on tumor progression and metastasis. PMID- 27353034 TI - Ofatumumab-associated acute respiratory manifestations: clinical characteristics and treatment. PMID- 27353035 TI - Myeloid neoplasms after chemotherapy and PRRT: myth and reality. AB - Peptide receptor radionuclide therapy (PRRT) with (90)Y-octreotide or (177)Lu octreotate is an effective treatment for inoperable or metastatic neuroendocrine tumors (NETs), particularly well-differentiated gastroenteropancreatic or bronchopulmonary NETs. PRRT is generally extremely well tolerated, with modest toxicity to target organs, kidney and bone marrow. Nevertheless, a priori concerns regarding long-term effects lead clinicians such as Brieau and coworkers, in this ERC issue, to ascribe to the combination of alkylating agents and PRRT the apparently high occurrence (n=4) of myeloproliferative events (therapy-related myeloid neoplasms (t-MNs)) in a small cohort of 20 progressive, advanced digestive NETs treated with PRRT after chemotherapy. Anecdotal reports of myelotoxic events should be placed in the correct perspective of larger series, where the reported incidence of these events is ~2%, with the aim of promoting a balanced awareness of the issue and unbiased and reasonable overall conclusions. For a comprehensive definition of the issue, we provide an evaluation of the occurrence of t-MN in patients treated with various myelotoxic treatments. PMID- 27353036 TI - MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors. AB - Temozolomide (TEM) showed encouraging results in well-differentiated pancreatic neuroendocrine tumors (WDPNETs). Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and MGMT promoter methylation within tumors correlate with a better outcome under TEM-based chemotherapy in glioblastoma. We aimed to assess whether MGMT expression and MGMT promoter methylation could help predict the efficacy of TEM-based chemotherapy in patients with WDPNET. Consecutive patients with progressive WDPNET and/or liver involvement over 50% who received TEM between 2006 and 2012 were retrospectively studied. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Nuclear expression of MGMT was assessed by immunochemistry (H-score, 0-300) and MGMT promoter methylation by pyrosequencing. Forty-three patients (21 men, 58years (27-84)) with grade 1 WDPNET (n=6) or 2 (n=36) were analyzed. Objective response, stable disease, and progression rates were seen in 17 patients (39.5%), 18 patients (41.9%), and 8 patients (18.6%), respectively. Low MGMT expression (<=50) was associated with radiological objective response (P=0.04) and better progression-free survival (PFS) (HR=0.35 (0.15-0.81), P=0.01). Disease control rate at 18months of treatment remained satisfying with an MGMT score up to 100 (74%) but dropped with a higher expression. High MGMT promoter methylation was associated with a low MGMT expression and longer PFS (HR=0.37 (0.29-1.08), P=0.05). Low MGMT score (<=50) appears to predict an objective tumor response, whereas an intermediate MGMT score (50-100) seems to be associated with prolonged stable disease. PMID- 27353037 TI - T3/TRs axis in hepatocellular carcinoma: new concepts for an old pair. AB - Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and its burden is expected to further increase in the next years. Chronic inflammation, induced by multiple viruses or metabolic alterations, and epigenetic and genetic modifications, cooperate in cancer development via a combination of common and distinct aetiology-specific pathways. In spite of the advances of classical therapies, the prognosis of this neoplasm has not considerably improved over the past few years. The advent of targeted therapies and the approval of the systemic treatment of advanced HCC with the kinase inhibitor sorafenib have provided some hope for the future. However, the benefits obtained from this treatment are still disappointing, as it extends the median life expectancy of patients by only few months. It is thus mandatory to find alternative effective treatments. Although the role played by thyroid hormones (THs) and their nuclear receptors (TRs) in human cancer is still unclear, mounting evidence indicates that they behave as oncosuppressors in HCC. However, the molecular mechanisms by which they exert this effect and the consequence of their activation following ligand binding on HCC progression remain elusive. In this review, we re-evaluate the existing evidence of the role of TH/TRs in HCC development; we will also discuss how TR alterations could affect fundamental biological processes, such as hepatocyte proliferation and differentiation, and consequently HCC progression. Finally, we will discuss if and how TRs can be foreseen as therapeutic targets in HCC and whether selective TR modulation by TH analogues may hold promise for HCC treatment. PMID- 27353038 TI - Angiopoietin-2 promotes ER+ breast cancer cell survival in bone marrow niche. AB - In estrogen receptor-positive (ER+) breast cancer, it is recognized that metastases may develop after a long period of dormancy. Bone marrow (BM) vascular niche is where the dormant tumor cells are most likely to reside. So far, it is not fully understood why the dormant tumor cells become proliferative and eventually generate tumor. We hypothesized that therapeutic or menopause-related estrogen depletion may be the switch behind dormant ER+ tumor cell awakening in BM. We utilized an existing experimental model of BM endothelial niche that can simulate ER+ tumor cell dormancy to test our hypothesis. In results, estrogen depletion paradoxically promoted ER+ tumor cell proliferation in the BM endothelial niche, and their molecular phenotype shifted from dormant to awaken. Following estrogen depletion, the BM niche cells produced angiopoietin-2 (ANGPT2), which destabilized niche endothelium by interfering ANGPT1/Tie2 signaling, and promoted ER+ tumor cell survival under estrogen deficiency via cell surface integrin &1. Knockdown of ANGPT2 completely negated ER+ tumor cell awakening in the niche. Furthermore, ANGPT2 expression in ER+ tumor human samples was associated with increased risk of distant metastasis only in those who underwent adjuvant estrogen depletion therapy, not in those who did not undergo adjuvant therapy. In conclusion, we demonstrate that ANGPT2 signaling activated after estrogen depletion paradoxically triggers ER+ tumor cell awakening from dormancy in their BM niche, partly indirectly via endothelial Tie2 receptor and partly directly via tumor cell surface integrin &1. PMID- 27353039 TI - MicroRNAs associated with small bowel neuroendocrine tumours and their metastases. AB - Novel molecular analytes are needed in small bowel neuroendocrine tumours (SBNETs) to better determine disease aggressiveness and predict treatment response. In this study, we aimed to profile the global miRNome of SBNETs, and identify microRNAs (miRNAs) involved in tumour progression for use as potential biomarkers. Two independent miRNA profiling experiments were performed (n=90), including primary SBNETs (n=28), adjacent normal small bowel (NSB; n=14), matched lymph node (LN) metastases (n=24), normal LNs (n=7), normal liver (n=2) and liver metastases (n=15). We then evaluated potentially targeted genes by performing integrated computational analyses. We discovered 39 miRNAs significantly deregulated in SBNETs compared with adjacent NSB. The most upregulated (miR-204 5p, miR-7-5p and miR-375) were confirmed by qRT-PCR. Two miRNAs (miR-1 and miR 143-3p) were significantly downregulated in LN and liver metastases compared with primary tumours. Furthermore, we identified upregulated gene targets for miR-1 and miR-143-3p in an existing SBNET dataset, which could contribute to disease progression, and show that these miRNAs directly regulate FOSB and NUAK2 oncogenes. Our study represents the largest global miRNA profiling of SBNETs using matched primary tumour and metastatic samples. We revealed novel miRNAs deregulated during SBNET disease progression, and important miRNA-mRNA interactions. These miRNAs have the potential to act as biomarkers for patient stratification and may also be able to guide treatment decisions. Further experiments to define molecular mechanisms and validate these miRNAs in larger tissue cohorts and in biofluids are now warranted. PMID- 27353040 TI - A Research Protocol to Test the Effectiveness of Text Messaging and Reminder Calls to Increase Service Use Referrals in a Community Engagement Program. AB - BACKGROUND: Mobile phoned-based interventions have been increasingly used in clinical populations to improve health and health care delivery. The literature has shown that mobile phone-based text messages (short message service, SMS) are instantaneous, cost effective, and have less chance of being misplaced. Studies using mobile phone based-text messages have reported text messages as effective reminders that have resulted in increased appointment attendance, adherence to treatment, and better self-management. There have been no reports of adverse events when using text messaging in terms of misreading or misinterpreting data, transmitting inaccurate data, losing verbal or nonverbal communication cues, privacy issues, or failure or delay in message delivery. However, the literature has cited a need for personalized messages that are more responsive to individual needs. In addition, there has been a dearth of information on the use of reminders in nonclinical populations. OBJECTIVE: The goal of this study is to assess the effectiveness of adding reminders in the form of text messaging versus reminder calls versus text messages and reminder calls to increase use of service referrals provided through community outreach. METHODS: A total of 300 participants will be recruited for the study. Each participant will be randomized to one of three arms: a group that receives only reminder calls (CALLSONLY); a group that receives only text message reminders (TEXTONLY); and a group that receives both reminder calls and text messages (CALLS+TEXT). All groups will receive their reminder intervention on the 15th and 45th day after baseline when they receive medical and social service referrals from the community health workers (CHWs). A standard script will be used to administer the call and text reminders and a 15-item telephone-based satisfaction survey will be administered to assess the participant satisfaction with the process of receiving periodic reminders. RESULTS: The study is in the recruitment and follow-up phase. The authors anticipate completion of recruitment, interventions, and data entry by July 2016. Preliminary results are expected to be available by September 2016. CONCLUSIONS: This study will provide an opportunity to test the effectiveness of mobile-based interventions on nonclinical, community-recruited populations. In particular, such a protocol would increase the effectiveness of a community-based engagement program by instating a formal reminder system for all program members who receive social and/or medical service referrals during outreach in the community. Findings from this study would guide the development and implementation of reminder protocols for community-based engagement programs nationwide. PMID- 27353041 TI - Lipid extraction mediates aggregation of carbon nanospheres in pulmonary surfactant monolayers. AB - Increasing evidence indicates that carbon nanoparticles (CNPs), which mainly originate from incomplete combustion of fossil fuels, have an adverse impact on the respiratory system. Recent in vivo experiments have shown that the pulmonary toxicity of CNPs is attributed to their aggregation in pulmonary surfactant monolayers (PSMs) while the underlying mechanism of aggregation remains unclear. Here, by performing coarse grained molecular dynamics simulations, we demonstrate for the first time that the aggregation of carbon nanospheres (CNSs) in PSMs is in fact size-dependent and mediated by lipid extractions. Upon CNS deposition, neighbouring lipid molecules are extracted from PSMs to cover CNSs from the top side. The extracted lipids induce clustering of CNSs to maximize the CNS-lipid interaction, by forming inverse micelles to wrap the aggregated CNSs cooperatively. The formed CNS clusters perturb the molecule structure of the PSM and thus affect its biofunction on respiration. Our simulations show that during the expiration process, CNSs form clusters that perturb the mechanical properties of the PSM in a manner depending on the CNS size. With deep inspiration, a high concentration of large CNSs may induce PSM rupture and thus have a potential impact on its biophysical properties. PMID- 27353042 TI - Trials of Zika vaccine are set to begin in North America. PMID- 27353043 TI - Experience of a multidisciplinary task force with exome sequencing for Mendelian disorders. AB - BACKGROUND: In order to optimally integrate the use of high-throughput sequencing (HTS) as a tool in clinical diagnostics of likely monogenic disorders, we have created a multidisciplinary "Genome Clinic Task Force" at the University Hospitals of Geneva, which is composed of clinical and molecular geneticists, bioinformaticians, technicians, bioethicists, and a coordinator. METHODS AND RESULTS: We have implemented whole exome sequencing (WES) with subsequent targeted bioinformatics analysis of gene lists for specific disorders. Clinical cases of heterogeneous Mendelian disorders that could potentially benefit from HTS are presented and discussed during the sessions of the task force. Debate concerning the interpretation of identified variants and the content of the final report constitutes a major part of the task force's work. Furthermore, issues related to bioethics, genetic counseling, quality control, and reimbursement are also addressed. CONCLUSIONS: This multidisciplinary task force has enabled us to create a platform for regular exchanges between all involved experts in order to deal with the multiple complex issues related to HTS in clinical practice and to continuously improve the diagnostic use of HTS. In addition, this task force was instrumental to formally approve the reimbursement of HTS for molecular diagnosis of Mendelian disorders in Switzerland. PMID- 27353044 TI - CXCL16 Deficiency Attenuates Renal Injury and Fibrosis in Salt-Sensitive Hypertension. AB - Inflammation plays an important role in the pathogenesis of hypertensive kidney disease. However, the molecular mechanisms underlying the induction of inflammation are not completely understood. We have found that CXCL16 is induced in the kidney in deoxycorticosterone acetate (DOCA)-salt hypertension. Here we examined whether CXCL16 is involved in DOCA-salt-induced renal inflammation and fibrosis. Wild-type and CXCL16 knockout mice were subjected to uninephrectomy and DOCA-salt treatment for 3 weeks. There was no difference in blood pressure at baseline between wild-type and CXCL16 knockout mice. DOCA-salt treatment resulted in significant elevation in blood pressure that was comparable between wild-type and CXCL16 knockout mice. CXCL16 knockout mice exhibited less severe renal dysfunction, proteinuria, and fibrosis after DOCA-salt treatment compared with wild-type mice. CXCL16 deficiency attenuated extracellular matrix protein production and suppressed bone marrow-derived fibroblast accumulation and myofibroblast formation in the kidneys following DOCA-salt treatment. Furthermore, CXCL16 deficiency reduced macrophage and T cell infiltration into the kidneys in response to DOCA-salt hypertension. Taken together, our results indicate that CXCL16 plays a key role in the pathogenesis of renal injury and fibrosis in salt-sensitive hypertension through regulation of bone marrow-derived fibroblast accumulation and macrophage and T cell infiltration. PMID- 27353045 TI - Occupancy of Nociceptin/Orphanin FQ Peptide Receptors by the Antagonist LY2940094 in Rats and Healthy Human Subjects. AB - Therapeutic benefits from nociceptin opioid peptide receptor (NOP) antagonism were proposed for obesity, eating disorders, and depression. LY2940094 ([2-[4-[(2 chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3 methyl-pyrazol-1-yl]-3-pyridyl]methanol) is a novel, orally bioavailable, potent, and selective NOP antagonist. We studied NOP receptor occupancy (RO) after single oral LY2940094 doses in rat hypothalamus and human brain by use of liquid chromatography with tandem mass spectrometry (LC-MS/MS) (LSN2810397) and positron emission tomography (PET) ([(11)C]NOP-1A) tracers, respectively. A bolus plus constant infusion tracer protocol with PET was employed in humans at 2.5 and 26.5 hours after administration of the LY2940094 dose. The RO was calculated from the change in regional distributional volume (VT) corrected for nondisplaceable volume using Lasson plots. The RO followed a simple Emax relationship to plasma LY2940094 concentration, reaching near complete occupancy in both species. For rat hypothalamus, the plasma concentration at half-maximum RO (EC50) was 5.8 ng/ml. In humans, LY2940094 was well tolerated and safe over the 4-40 mg dose range, and it peaked in plasma at 2 to 6 hours after a 1- to 2-hour lag, with approximate dose-proportional exposure. After 4-40 mg doses, NOP RO was similar across the prefrontal cortex, occipital cortex, putamen, and thalamus, with EC50 of 2.94 to 3.46 ng/ml, less than 2-fold lower than in rats. Over 4-40 mg doses, LY2940094 mean plasma levels at peak and 24 hours were 7.93-102 and 1.17-14.1 ng/ml, corresponding to the cross-region average NOP RO of 73%-97% and 28%-82%, respectively. The rat EC50 translates well to humans. LY2940094 readily penetrates the human brain, and a once-daily oral dose of 40 mg achieves sustainably high (>80%) NOP RO levels suitable for testing clinical efficacy. PMID- 27353046 TI - Stock enhancement or sea ranching? Insights from monitoring the genetic diversity, relatedness and effective population size in a seeded great scallop population (Pecten maximus). AB - The mass release of hatchery-propagated stocks raises numerous questions concerning its efficiency in terms of local recruitment and effect on the genetic diversity of wild populations. A seeding program, consisting of mass release of hatchery-produced juveniles in the local naturally occurring population of great scallops (Pecten maximus L.), was initiated in the early 1980s in the Bay of Brest (France). The present study aims at evaluating whether this seeding program leads to actual population enhancement, with detectable effects on genetic diversity and effective population size, or consists of sea ranching with limited genetic consequences on the wild stock. To address this question, microsatellite based genetic monitoring of three hatchery-born and naturally recruited populations was conducted over a 5-year period. Results showed a limited reduction in allelic richness but a strong alteration of allelic frequencies in hatchery populations, while genetic diversity appeared very stable over time in the wild populations. A temporal increase in relatedness was observed in both cultured stock and wild populations. Effective population size (Ne) estimates were low and variable in the wild population. Moreover, the application of the Ryman-Laikre model suggested a high contribution of hatchery-born scallops to the reproductive output of the wild population. Overall, the data suggest that the main objective of the seeding program, which is stock enhancement, is fulfilled. Moreover, gene flow from surrounding populations and/or the reproductive input of undetected sub-populations within the bay may buffer the Ryman-Laikre effect and ensure the retention of the local genetic variability. PMID- 27353047 TI - Prediction and estimation of effective population size. AB - Effective population size (Ne) is a key parameter in population genetics. It has important applications in evolutionary biology, conservation genetics and plant and animal breeding, because it measures the rates of genetic drift and inbreeding and affects the efficacy of systematic evolutionary forces, such as mutation, selection and migration. We review the developments in predictive equations and estimation methodologies of effective size. In the prediction part, we focus on the equations for populations with different modes of reproduction, for populations under selection for unlinked or linked loci and for the specific applications to conservation genetics. In the estimation part, we focus on methods developed for estimating the current or recent effective size from molecular marker or sequence data. We discuss some underdeveloped areas in predicting and estimating Ne for future research. PMID- 27353048 TI - Comparative genomics analysis of the companion mechanisms of Bacillus thuringiensis Bc601 and Bacillus endophyticus Hbe603 in bacterial consortium. AB - Bacillus thuringiensis and Bacillus endophyticus both act as the companion bacteria, which cooperate with Ketogulonigenium vulgare in vitamin C two-step fermentation. Two Bacillus species have different morphologies, swarming motility and 2-keto-L-gulonic acid productivities when they co-culture with K. vulgare. Here, we report the complete genome sequencing of B. thuringiensis Bc601 and eight plasmids of B. endophyticus Hbe603, and carry out the comparative genomics analysis. Consequently, B. thuringiensis Bc601, with greater ability of response to the external environment, has been found more two-component system, sporulation coat and peptidoglycan biosynthesis related proteins than B. endophyticus Hbe603, and B. endophyticus Hbe603, with greater ability of nutrients biosynthesis, has been found more alpha-galactosidase, propanoate, glutathione and inositol phosphate metabolism, and amino acid degradation related proteins than B. thuringiensis Bc601. Different ability of swarming motility, response to the external environment and nutrients biosynthesis may reflect different companion mechanisms of two Bacillus species. Comparative genomic analysis of B. endophyticus and B. thuringiensis enables us to further understand the cooperative mechanism with K. vulgare, and facilitate the optimization of bacterial consortium. PMID- 27353050 TI - Fusion for lumbar spinal stenosis? PMID- 27353049 TI - HIV-1 Sequence Data Coverage in Central East Africa from 1959 to 2013. AB - Central and Eastern African HIV sequence data have been most critical in understanding the establishment and evolution of the global HIV pandemic. Here we report on the extent of publicly available HIV genetic sequence data in the Los Alamos National Laboratory Sequence Database sampled from 1959 to 2013 from six African countries: Uganda, Kenya, Tanzania, Burundi, the Democratic Republic of Congo, and Rwanda. We have summarized these data, including HIV subtypes, the years sampled, and the genomic regions sequenced. We also provide curated alignments for this important geographic area in five HIV genomic regions with substantial coverage. PMID- 27353051 TI - Systems genetics reveals key genetic elements of drought induced gene regulation in diploid potato. AB - In plants, tolerance to drought stress is a result of numerous minor effect loci in which transcriptional regulation contributes significantly to the observed phenotypes. Under severe drought conditions, a major expression quantitative trait loci hotspot was identified on chromosome five in potato. A putative Nuclear factor y subunit C4 was identified as key candidate in the regulatory cascade in response to drought. Further investigation of the eQTL hotspots suggests a role for a putative Homeobox leucine zipper protein 12 in relation to drought in potato. Genes strongly co-expressed with Homeobox leucine zipper protein 12 were plant growth regulators responsive to water deficit stress in Arabidopsis thaliana, implying a possible conserved mechanism. Integrative analysis of genetic, genomic, phenotypic and transcriptomic data provided insights in the downstream functional components of the drought response. The abscisic acid- and environmental stress-inducible protein TAS14 was highly induced by severe drought in potato and acts as a reliable biomarker for the level of stress perceived by the plant. The systems genetics approach supported a role for multiple genes responsive to severe drought stress of Solanum tuberosum. The combination of gene regulatory networks, expression quantitative trait loci mapping and phenotypic analysis proved useful for candidate gene selection. PMID- 27353052 TI - Apocynin reduces blood pressure and restores the proper function of vascular endothelium in SHR. AB - This study has evaluated how the vascular endothelium of hypertensive rats chronically treated with apocynin affects acetylcholine (ACh), sodium nitroprusside (SNP), and phenylephrine (PE) action on the nitric oxide (NO) signal transduction pathway in endothelial (EC) and vascular smooth muscle cells. Treatment with apocynin significantly reduced the mean arterial pressure in spontaneously hypertensive rats (SHR). In addition, apocynin improved the impaired ACh hypotensive effect on SHR. Although systemic oxidative stress was high in SHR, SHR treated with apocynin and normotensive rats presented similar systemic oxidative stress levels. Endothelium significantly blunted PE contractions in intact aortas of treated SHR. The ACh effect was impaired in resistance arteries and aortas of SHR, but this same effect was improved in treated SHR. The SNP potency was higher in intact resistance arteries of treated SHR than in intact resistance arteries of untreated SHR. NO and calcium concentrations increased, whereas reactive oxygen species levels decreased in EC of treated SHR. Aortas of untreated and treated SHR did not differ in terms of sGC alpha or beta units expression. Aorta of treated SHR expressed higher eNOS levels as compared to aorta of untreated SHR. The study groups did not differ with respect to NOX1, NOXO1, or NOX4 expression. However, treatment with apocynin normalized overexpression of NOX2 and its subunit p47phox in aortas of SHR. Based on all the results presented in this study, we suggest apocynin increases NO biovailability by different mechanisms, restoring the proper function of vascular endothelium in SHR. PMID- 27353054 TI - Considerations of statistical power and risk of bias question the strength of nicotine replacement therapy's effectiveness. PMID- 27353053 TI - Pomalidomide mitigates neuronal loss, neuroinflammation, and behavioral impairments induced by traumatic brain injury in rat. AB - BACKGROUND: Traumatic brain injury (TBI) is a global health concern that typically causes emotional disturbances and cognitive dysfunction. Secondary pathologies following TBI may be associated with chronic neurodegenerative disorders and an enhanced likelihood of developing dementia-like disease in later life. There are currently no approved drugs for mitigating the acute or chronic effects of TBI. METHODS: The effects of the drug pomalidomide (Pom), an FDA approved immunomodulatory agent, were evaluated in a rat model of moderate to severe TBI induced by controlled cortical impact. Post-TBI intravenous administration of Pom (0.5 mg/kg at 5 or 7 h and 0.1 mg/kg at 5 h) was evaluated on functional and histological measures that included motor function, fine more coordination, somatosensory function, lesion volume, cortical neurodegeneration, neuronal apoptosis, and the induction of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6). RESULTS: Pom 0.5 mg/kg administration at 5 h, but not at 7 h post-TBI, significantly mitigated the TBI-induced injury volume and functional impairments, neurodegeneration, neuronal apoptosis, and cytokine mRNA and protein induction. To evaluate underlying mechanisms, the actions of Pom on neuronal survival, microglial activation, and the induction of TNF-alpha were assessed in mixed cortical cultures following a glutamate challenge. Pom dose-dependently ameliorated glutamate-mediated cytotoxic effects on cell viability and reduced microglial cell activation, significantly attenuating the induction of TNF-alpha. CONCLUSIONS: Post-injury treatment with a single Pom dose within 5 h significantly reduced functional impairments in a well-characterized animal model of TBI. Pom decreased the injury lesion volume, augmented neuronal survival, and provided anti-inflammatory properties. These findings strongly support the further evaluation and optimization of Pom for potential use in clinical TBI. PMID- 27353055 TI - FibroScan, APRI, FIB4, and GUCI: Role in prediction of fibrosis and response to therapy in Egyptian patients with HCV infection. AB - BACKGROUND AND STUDY AIMS: Multiple noninvasive methods have been used successfully in the prediction of fibrosis. However, their role in the prediction of response to hepatitis C virus (HCV) antiviral therapy is debatable. The aim of this study was to validate and compare the diagnostic performance of FibroScan, APRI (aspartate aminotransferase (AST)-to-platelet ratio index), FIB4, and GUCI (Goteborg University Cirrhosis Index) for the prediction of hepatic fibrosis and treatment outcome in HCV-infected patients receiving pegylated interferon and ribavirin (PEG-IFN/ribavirin). PATIENTS AND METHODS: This study included 182 Egyptian patients with chronic HCV infection. They were classified into two groups based on the stages of fibrosis: mild to significant fibrosis (F1-F2) and advanced fibrosis (F3-F4). The APRI, FIB4, and GUCI scores were calculated before the antiviral treatment. The FibroScan was performed for all patients before treatment. RESULTS: Stiffness and FIB4 have greater sensitivity and specificity in detecting advanced fibrosis of 80%, 77% and 88%, 84%, respectively. Based on multivariate regression analysis, FIB4, body mass index (BMI), and alpha fetoprotein (AFP) level were found to be statistically significant predictors of advanced fibrosis (p-value: 0.000, 0.011, and 0.001, respectively) with odds ratio (OR: 3.184, 1.170, and 1.241, respectively). With respect to virological response, the stiffness, APRI, FIB4, and GUCI were significantly lower in sustained virological responders. However, these are not good predictors of response to PEG-IFN/ribavirin therapy. AFP was the only statistically significant predictor of response (p=0.002) with OR of 1.141 in multivariate regression analysis. CONCLUSION: FibroScan and noninvasive scores such as APRI, FIB4, and GUCI can be used as good predictors of liver fibrosis in chronic hepatitis C. However, they are not good predictors of response to PEG-IFN/ribavirin therapy. PMID- 27353056 TI - Left Atrial Compression Caused by an Intrapericardial Hematoma after Coronary Artery Bypass Graft Surgery. AB - BACKGROUND: Left atrial compression (LAC) is an uncommon condition that causes left ventricular inflow obstruction. The clinical and pathologic features are similar to those of mitral stenosis. Impaired left ventricular filling may cause hypotension, syncope, or shock. The increased left atrial pressure causes retrograde increase of the pressure throughout the pulmonary circulation with subsequent signs of congestion. CASE REPORT: An 84-year-old man presented with LAC caused by a focal tamponade related to a pericardial hematoma as a complication of coronary artery bypass graft (CABG) surgery. The formation of the hematoma occurred 3 weeks postsurgery. The echocardiographic study before discharge at day 12 after CABG surgery showed neither a focal hematoma nor a tamponade. The diagnosis was made 6 days later. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Intrapericardial tamponade caused by bleeding is a known complication of CABG surgery in the early postoperative stage. However, emergency physicians should be aware that a postoperative hematoma may also present as a focal tamponade because of postoperative adhesion by scar formation. The literature of LAC is limited. The most reported causes of LAC are compression caused by structures of the gastrointestinal tract, followed by thoracic aortic pathology. A Medline search for the terms "left atrial compression and hematoma" and "left atrial compression and intrapericardial hematoma" found only 31 and 4 hits, respectively. We also briefly discuss the import role of bedside echocardiography in the diagnostic process of LAC in the emergency medicine department. PMID- 27353057 TI - Spontaneous Iliopsoas Hematoma. PMID- 27353058 TI - Thrombus-in-Transit: A Case for a Multidisciplinary Hospital-Based Pulmonary Embolism System of Care. AB - BACKGROUND: Venous thromboembolism, including pulmonary embolism (PE), is a common disease identified in the emergency department that carries significant morbidity and mortality. In its most severe form, PE is fulminant and characterized by cardiac arrest and death. CASE REPORT: In the midst of risk stratifying PE by using echocardiography to assess right ventricular function, thrombus-in-transit (free-floating clot in the right atrium or ventricle) may be seen. We present a case of a 49-year-old man diagnosed with an acute saddle PE who was incidentally found to have a thrombus-in-transit and patent foramen ovale and required open thrombectomy. Identification of these additional potentially life-threatening features was possible only due to our availability of risk stratification resources, specifically bedside echocardiography. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Albeit rare, with a reported incidence estimated at 4%, the presence of thrombus-in-transit may change emergent clinical management. A multidisciplinary team of resources should be considered emergently as part of a hospital-based PE system of care. PMID- 27353059 TI - Associated Injuries in Skeletally Immature Children with Pelvic Fractures. AB - BACKGROUND: Pediatric pelvic fractures are rare injuries resulting from high energy mechanisms that warrant an extensive work-up for associated injuries. OBJECTIVES: We performed a retrospective study to review concomitant injuries in children who suffered a pelvic fracture and have an open triradiate cartilage. METHODS: Using a database, pediatric pelvic fractures presenting to the authors' institution were extracted. Radiographs and computed tomography scans were reviewed, ensuring that triradiate cartilages were not fused and the pelvic injuries were classified using the Modified Torode Classification. Epidemiologic data extracted included Glasgow Coma Scale (GCS), Injury Severity Score (ISS), and Abbreviated Injury Score (AIS). RESULTS: Sixty patients met the inclusion criteria, and their average age was 8.3 years (range 2-14 years). There were no mortalities. The most common mechanism of injury was a vehicle striking a pedestrian. There were no significant correlations between GCS, ISS, and AIS. All 60 children (100%) suffered extremity injuries. Nineteen patients required surgical orthopedic intervention, and 6 required operative stabilization of the pelvis. Patients who were struck by a motor vehicle were more likely to have multiple pelvic fractures (p < 0.05). Patients with multiple pelvic fractures were more likely to require orthopaedic surgical intervention and require a blood transfusion (p < 0.05). Patients who had type III-B or IV fractures were more likely to require a transfusion than patients with III-A fracture (p < 0.05). CONCLUSIONS: Patients sustaining fractures to an immature pelvis are likely to have additional injuries, which may be fatal or disabling if not diagnosed in a timely manner. PMID- 27353060 TI - Vein of Galen Malformation. PMID- 27353061 TI - Virological response and resistance profile in HIV-1-infected patients starting darunavir-containing regimens. AB - OBJECTIVES: We evaluated the virological response in patients starting a regimen based on darunavir/ritonavir (DRV/r), which is currently the most widely used ritonavir-boosted protease inhibitor. METHODS: Data from 206 drug-naive and 327 PI-experienced patients starting DRV/r 600/100 mg twice daily (DRV600) or 800/100 mg once daily (DRV800) were examined. The probabilities of virological success (VS) and virological rebound (VR) were evaluated in survival analyses. Baseline DRV/r resistance and its evolution at failure were also examined. RESULTS: DRV600 was preferentially administered in patients with complex requirements (older age, higher viraemia, lower CD4 cell count and DRV/PI resistance) compared with DRV800. By 12 months, the probability of achieving VS was 93.2% and 84.3% in drug naive and PI-experienced patients, respectively. The higher the baseline viraemia, the longer was the time required to achieve VS, both in drug-naive patients [>500 000 HIV-1 RNA copies/mL: median [interquartile range (IQR)] 6.1 (5.1-10.3) months; 100 000-500 000 copies/mL: median (IQR) 4.9 (3.8-6.1) months; <100 000 copies/mL: median (IQR) 3.9 (3.5-4.8) months; P < 0.001] and in PI experienced patients [>=100 000 copies/mL: median (IQR) 7.2 (5.7-11.6) months; <100 000 copies/mL: median (IQR) 2.8 (2.4-3.3) months; P < 0.001]. In PI experienced patients, the probability of VR was higher for higher viraemia levels (22.3% for >=100 000 copies/ml vs. 9.7% for <100 000 copies/mL; P = 0.007). Baseline resistance did not affect the virological response. At failure, a high percentage of patients maintained virus susceptible to all PIs (drug-naive: 95%; PI-experienced: 80%). Despite being used more often in patients with more complex requirements, DRV600 performed as well as DRV800. CONCLUSIONS: In clinical practice, use of DRV/r (with its flexible dosage) results in high rates of virological response. These data support the use of PI/r in patients whose characteristics require potent drugs with a high genetic barrier. PMID- 27353062 TI - Fatigue failure of dental implants in simulated intraoral media. AB - Metallic dental implants are exposed to various intraoral environments and repetitive loads during service. Relatively few studies have systematically addressed the potential influence of the environment on the mechanical integrity of the implants, which is therefore the subject of this study. Four media (groups) were selected for room temperature testing, namely dry air, saliva substitute, same with 250ppm of fluoride, and saline solution (0.9%). Monolithic Ti-6Al-4V implants were loaded until fracture, using random spectrum loading. The study reveals that the only aggressive medium of all is the saline solution, as it shortens significantly the spectrum fatigue life of the implants. The quantitative scanning electron fractographic analysis indicates that all the tested implants grew fatigue cracks of similar lengths prior to catastrophic fracture. However, the average crack growth rate in the saline medium was found to largely exceed that in other media, suggesting a decreased fracture toughness. The notion of a characteristic timescale for environmental degradation was proposed to explain the results of our spectrum tests that blend randomly low and high cycle fatigue. Random spectrum fatigue testing is powerful technique to assess and compare the mechanical performance of dental implants for various designs and/or environments. PMID- 27353063 TI - Chronic Chagas cardiopathy in Chile. Importance of Trypanosoma cruzi burden and clinical evaluation. AB - Currently there are no biological markers to indicate which individuals with chronic indeterminate period of Chagas disease develop heart disease and who will remain all his life in this phase. The aim of this survey was to determine if Trypanosoma cruzi burden is related to the presence of heart disease in patients with chronic Chagas disease. 200 patients who had not been treated, 100 with cardiopathy and 100 without, groups A and B respectively, were submitted to clinical study and electrocardiogram, Echo-Doppler was performed for group A in which all important known causes of cardiopathy were discarded. In both groups xenodiagnosis, conventional PCR and quantitative PCR were undertaken. The 100 cardiopaths had 133 electrocardiographic alterations most of them in grade II of the New York Heart Association classification. 98 cardiopaths were classified in grade I by Echo-Doppler and only 2 cases were in grade III due to low ejection fraction. The difference in average parasitemia in patients of group A and B was not significant and no statistically differences were observed between average parasitemia of cardiopaths grade II versus grade I of NYHA. This results allow to characterize same clinical, electrocardiographical and parasitological features in chagasic cardiopaths of Chile. PMID- 27353065 TI - Disentangling the relationships between staff nurses' workplace empowerment and job satisfaction. AB - AIM: The primary aim of this study was to examine the relationships between structural empowerment, psychological empowerment and job satisfaction among staff nurses, after controlling for their leaders' use of empowering behaviours. BACKGROUND: Nurses' job satisfaction is a critical factor in health-care organisations because of its association with nurse turnover and quality of patient care. Nurses continue to report high levels of job dissatisfaction. METHODS: Cross-sectional data for 1007 Canadian staff nurses were analysed using hierarchical multiple regression. RESULTS: Structural empowerment was the strongest independent predictor of job satisfaction, followed by leader empowering behaviours and psychological empowerment. After accounting for the effects of structural empowerment and leader empowering behaviours, the four dimensions of psychological empowerment showed only small independent effects on job satisfaction. Psychological empowerment did not mediate the effects of structural empowerment on job satisfaction. CONCLUSION: Nurses' job satisfaction is most influenced by their access to organisational empowerment structures. Leader empowering behaviours, structural empowerment, and psychological empowerment, operating together, enhance nurses' job satisfaction. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse leaders should use a variety of empowerment strategies that are important to nurses' job satisfaction and potentially to the quality of patient care and nurse turnover. PMID- 27353064 TI - Novel proteases from the genome of the carnivorous plant Drosera capensis: Structural prediction and comparative analysis. AB - In his 1875 monograph on insectivorous plants, Darwin described the feeding reactions of Drosera flypaper traps and predicted that their secretions contained a "ferment" similar to mammalian pepsin, an aspartic protease. Here we report a high-quality draft genome sequence for the cape sundew, Drosera capensis, the first genome of a carnivorous plant from order Caryophyllales, which also includes the Venus flytrap (Dionaea) and the tropical pitcher plants (Nepenthes). This species was selected in part for its hardiness and ease of cultivation, making it an excellent model organism for further investigations of plant carnivory. Analysis of predicted protein sequences yields genes encoding proteases homologous to those found in other plants, some of which display sequence and structural features that suggest novel functionalities. Because the sequence similarity to proteins of known structure is in most cases too low for traditional homology modeling, 3D structures of representative proteases are predicted using comparative modeling with all-atom refinement. Although the overall folds and active residues for these proteins are conserved, we find structural and sequence differences consistent with a diversity of substrate recognition patterns. Finally, we predict differences in substrate specificities using in silico experiments, providing targets for structure/function studies of novel enzymes with biological and technological significance. Proteins 2016; 84:1517-1533. (c) 2016 Wiley Periodicals, Inc. PMID- 27353066 TI - Two-Dimensional Speckle Tracking of the Fetal Heart: A Practical Step-by-Step Approach for the Fetal Sonologist. AB - Various approaches to 2-dimensional speckle tracking have been used to evaluate left ventricular function and deformation in the fetus, child, and adult. In 2015, because of differences in imaging devices and analytical programs, the cardiology community published a consensus document proposing standards for pediatric/adult deformation imaging using 2-dimensional speckle tracking. The understanding and application of deformation imaging in the fetus have been limited by a lack of uniform software, terminology, techniques, and display. This article provides a practical, step-by-step approach for deformation analysis of the fetal heart using offline software that is independent of specific ultrasound vendors. PMID- 27353067 TI - Expected Sonographic Appearance of the Spleen in Children and Young Adults With Sickle Cell Disease: An Update. AB - OBJECTIVES: To update the imaging literature regarding spleen appearances in young patients with sickle cell disease (SCD). METHODS: We conducted a retrospective study and included 112 patients age 0 to 21 years with SCD who had at least 1 abdominal sonogram at our institution between 1999 and 2011. Radiologic findings were compared between risk groups by chi(2) analysis. Findings were correlated with other imaging modalities when available. RESULTS: In our cohort, 35.7% of patients had autosplenectomy, and 8.0% had undergone surgical splenectomy. Only 5.0% of individuals age 0 to 5 years had autosplenectomy. In those who had not undergone surgical splenectomy or autosplenectomy, 76.2% had echogenic spleens, heterogeneous-appearing spleens, or both, and patients with the homozygous sickle cell anemia (HbSS) genotype were more likely to have an abnormal spleen echo texture. Patients treated with transfusions had echogenic spleens and had a higher frequency of splenic regeneration nodules. Most patients (80%) with splenomegaly did not require surgical splenectomy after 5.7 years of follow-up. CONCLUSIONS: Twenty years ago, children with HbSS SCD were expected to have autosplenectomy by age 5 years. There have been changes in the radiologic appearance of the spleen in patients with SDC, likely due to improved supportive care and the use of acute and chronic transfusion therapy. We found that autosplenectomy is rare by age 5 years, and during childhood and adolescence, the spleen typically appears echogenic, heterogeneous, or both, depending on disease severity. PMID- 27353068 TI - Carotid-Ventricular Coupling During Exercise: A Pilot Study. AB - OBJECTIVES: To evaluate carotid elasticity and left ventricular elastance during a graded bicycle semisupine exercise test in patients with known or suspected coronary artery disease and compare them with a control group of healthy young volunteers. METHODS: Thirty-six elderly patients and 18 young healthy volunteers were recruited. The right carotid diameter was estimated by an automatic system applied to B-mode sonographic sequences, central mean blood and pulse pressures by radial artery tonometry, and cardiac volumes by 2-dimensional transthoracic echocardiography; from these direct measurements, the carotid cross-sectional distensibility coefficient and left ventricular elastance index were obtained. Analyses were performed at rest, at peak stress, and during the recovery phase. RESULTS: The elderly patients included 20 men (mean age +/- SD, 61 +/- 8 years); the volunteers included 9 men (mean age, 34 +/- 3 years). The mean blood pressure (at rest: patients, 97 +/- 7 mm Hg; controls, 93 +/- 9 mm Hg; not significant) increased similarly in both groups during exercise and decreased during the recovery phase. The diameter was higher in patients than controls (7.5 +/- 1.1 versus 6.2 +/- 0.5 mm) and increased significantly with exercise only in the latter group (at peak: 6.5 +/- 0.6 mm; P < .05). The distensibility coefficient and elastance index were lower in patients than controls during the test phases [at rest: 24.5 +/- 10.2 versus 60.8 +/- 21.3 * 10(-3)/kPa and 3.6 +/- 1.4 versus 1.6 +/- 0.8 mm Hg/(mL/m(2))] and mostly changed in the controls, showing a decreased distensibility coefficient (peak: 40.6 +/- 15.1 * 10(-3)/kPa) and an increased elastance index [peak: 5.9 +/- 2.8 mm Hg/(mL/m(2))]. CONCLUSIONS: In older patients with multiple cardiovascular risk factors or established coronary artery disease, an abnormal carotid-ventricular adaptation to exercise was observed when compared to young healthy individuals. PMID- 27353069 TI - A New Sonographic Weight Estimation Formula for Small-for-Gestational-Age Fetuses. AB - OBJECTIVES: The purpose of this study was to develop a new specific weight estimation formula for small-for-gestational-age (SGA) fetuses that differentiated between symmetric and asymmetric growth patterns. METHODS: A statistical estimation technique known as component-wise gradient boosting was applied to a group of 898 SGA fetuses (symmetric, n = 750; asymmetric, n = 148). A new formula was derived from the data obtained and was then compared to other commonly used equations. RESULTS: The new formula derived is as follows: estimated fetal weight = e^[1.3734627 + 0.0057133 * biparietal diameter + 0.0011282 * head circumference + 0.0201147 * abdominal circumference + 0.0183081 * femur length - 0.0000177 * biparietal diameter(2) - 0.0000018 * head circumference(2) - 0.0000297 * abdominal circumference(2) -0.0001007 * femur length(2) + 0.0397563 * I(sex = male) + 0.0064505 * gestational age (days) + 0.0096528 * I(SGA = asymmetric)], where the function I denotes an indicator function, which is 1 if the expression is fulfilled (sex = male; SGA type = asymmetric) and otherwise 0. In the whole study group and the 2 subgroups, the new formula showed the lowest median absolute percentage error, mean percentage error, and random error and the best distribution of absolute percentage errors within prespecified error bounds. CONCLUSIONS: The new formula substantially improves weight estimation in SGA fetuses. PMID- 27353070 TI - Echocardiographic Findings of an Anomalous Origin of the Left Coronary Artery in Children and Adolescents: Real or Fake? AB - An anomalous origin of the left coronary artery (LCA) is a relatively uncommon congenital heart defect that can lead to myocardial ischemia and sudden cardiac death. An LCA arising from the pulmonary artery and an LCA arising from the opposite sinus of Valsalva are the common types of anomalous origins of the LCA. Echocardiographic assessment of the coronary arteries is an important component of the routine cardiovascular evaluation, but echocardiographic "pseudo images" of LCA origination can be present in some patients. Detection of an anomalous origin of the LCA remains a challenge to sonographers. PMID- 27353071 TI - Sonographic Elastography of Mastitis. AB - Sonographic elastography has been shown to be a useful imaging modality in characterizing breast lesions as benign or malignant. However, in preliminary research, mastitis has given false-positive findings on both strain and shear wave elastography. In this article, we review the findings in mastitis with and without abscess formation on both strain and shear wave elastography. The elastographic findings in all cases were suggestive of a malignancy according to published thresholds. In cases of mastitis with abscess formation, there is a characteristic appearance, with a central very soft area (abscess cavity) and a very stiff outer rim (edema and inflammation). This appearance should raise the suspicion of mastitis with abscess formation, since these findings are rare in breast cancers. PMID- 27353072 TI - Ultrasound Quality Assurance for Singletons in the National Institute of Child Health and Human Development Fetal Growth Studies. AB - OBJECTIVES: To report on the ultrasound quality assurance program for the National Institute of Child Health and Human Development Fetal Growth Studies and describe both its advantages and generalizability. METHODS: After training on an ultrasound system and software, research sonographers were expected to capture blank (unmeasured) images in triplicate for crown-rump length, biparietal diameter, head circumference, abdominal circumference, and femur length. A primary expert sonographer was designated and validated. A 5% sample (n = 740 of 14,785 scans) was randomly selected in 3 distinct rounds from within strata of maternal body mass index (round 1 only), gestational age, and research site. Unmeasured images were extracted from selected scans and measured with the ultrasound software by an expert sonographer. Correlations and coefficients of variation (CVs) were calculated, and the within-measurement standard deviation (ie, technical error of the measurement), was calculated. RESULTS: The reliability between the site sonographers and the expert was high, with correlations exceeding 0.99 for all dimensions in all rounds. The CV % values showed low variability, with the percentage differences being less than 2%, except for abdominal circumference in rounds 2 and 3, in which it averaged about 3%. Correlations remained high (>0.90) with increasing fetal size; there was a monotonic increase in technical errors of the measurement but without a corresponding increase in the CV %. CONCLUSIONS: Using rigorous procedures for training sonographers, coupled with quality assurance oversight, we determined that the measurements acquired longitudinally for singletons are both accurate and reliable for establishment of an ultrasound standard for fetal growth. PMID- 27353073 TI - Treatment of Skin Inflammation with Benzoxaborole Phosphodiesterase Inhibitors: Selectivity, Cellular Activity, and Effect on Cytokines Associated with Skin Inflammation and Skin Architecture Changes. AB - Psoriasis and atopic dermatitis are skin diseases affecting millions of patients. Here, we characterize benzoxaborole phosphodiesterase (PDE)-4 inhibitors, a new topical class that has demonstrated therapeutic benefit for psoriasis and atopic dermatitis in phase 2 or phase 3 studies. Crisaborole [AN2728, 4-((1-hydroxy-1,3 dihydrobenzo[c][1,2]oxaborol-5-yl)oxy)benzonitrile], compd2 [2-ethoxy-6-((1 hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yl)oxy)nicotinonitrile], compd3 [6-((1 hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yl)oxy)-2-(2 isopropoxyethoxy)nicotinonitrile], and compd4 [5-chloro-6-((1-hydroxy-1,3 dihydrobenzo[c][1,2]oxaborol-5-yl)oxy)-2-((4-oxopentyl)oxy)nicotinonitrile] are potent PDE4 inhibitors with similar affinity for PDE4 isoforms and equivalent inhibition on the catalytic domain and the full-length enzyme. These benzoxaboroles are less active on other PDE isozymes. Compd4 binds to the catalytic domain of PDE4B2 with the oxaborole group chelating the catalytic bimetal and overlapping with the phosphate in cAMP during substrate hydrolysis, and the interaction extends into the adenine pocket. In cell culture, benzoxaborole PDE4 inhibitors suppress the release of tumor necrosis factor alpha, interleukin (IL)-23, IL-17, interferon-gamma, IL-4, IL-5, IL-13, and IL 22, and these cytokines contribute to the pathologic changes in skin structure and barrier functions as well as immune dysregulation in atopic dermatitis and psoriasis. Treatment with compd3 or N(6),2'-O-dibutyryladenosine 3',5'-cyclic monophosphate increases cAMP response element binding protein phosphorylation in human monocytes and decreases extracellular signal-regulated kinase phosphorylation in human T cells; these changes lead to reduced cytokine production and are among the mechanisms by which compd3 blocks cytokine release. Topical compd3 penetrates the skin and suppresses phorbol myristate acetate induced IL-13, IL-22, IL-17F, and IL-23 transcription and calcipotriol-induced thymic stromal lymphopoietin expression in mouse skin. Skin thinning is a major dose-limiting side effect of glucocorticoids. By contrast, repeated application of compd3 did not thin mouse skin. These findings show the potential benefits and safety of benzoxaborole PDE4 inhibitors for the treatment of psoriasis and atopic dermatitis. PMID- 27353074 TI - Class I Histone Deacetylase Inhibition for the Treatment of Sustained Atrial Fibrillation. AB - Current therapies are less effective for treating sustained/permanent versus paroxysmal atrial fibrillation (AF). We and others have previously shown that histone deacetylase (HDAC) inhibition reverses structural and electrical atrial remodeling in mice with inducible, paroxysmal-like AF. Here, we hypothesize an important, specific role for class I HDACs in determining structural atrial alterations during sustained AF. The class I HDAC inhibitor N-acetyldinaline [4 (acetylamino)-N-(2-amino-phenyl) benzamide] (CI-994) was administered for 2 weeks (1 mg/kg/day) to Hopx transgenic mice with atrial remodeling and inducible AF and to dogs with atrial tachypacing-induced sustained AF. Class I HDAC inhibition prevented atrial fibrosis and arrhythmia inducibility in mice. Dogs were divided into three groups: 1) sinus rhythm, 2) sustained AF plus vehicle, and 3) sustained AF plus CI-994. In group 3, the time in AF over 2 weeks was reduced by 30% compared with group 2, along with attenuated atrial fibrosis and intra-atrial adipocyte infiltration. Moreover, group 2 dogs had higher atrial and serum inflammatory cytokines, adipokines, and atrial immune cells and adipocytes compared with groups 1 and 3. On the other hand, groups 2 and 3 displayed similar left atrial size, ventricular function, and mitral regurgitation. Importantly, the same histologic alterations found in dogs with sustained AF and reversed by CI-994 were also present in atrial tissue from transplanted patients with chronic AF. This is the first evidence that, in sustained AF, class I HDAC inhibition can reduce the total time of fibrillation, atrial fibrosis, intra-atrial adipocytes, and immune cell infiltration without significant effects on cardiac function. PMID- 27353075 TI - The Chondrogenic Potential of Progenitor Cells Derived from Peripheral Blood: A Systematic Review. AB - An increasing number of studies have detected mesenchymal stromal cells (MSCs) and mesenchymal progenitor cells (MPCs) in the peripheral blood (PB). This study aimed to systematically review the possibility of using the PB as a source for chondrogenic progenitors. PubMed, the Web of Science, and Embase were searched for relevant articles. The findings of the studies were reviewed to evaluate the biological characteristics of PB-derived MSCs, chondrogenic MPCs, and their applications in cartilage repair. Thirty-six articles were included in the final analysis, 29 of which indicated that PB is a potential source for chondrogenic progenitor cells. Thirty-two studies reporting in vitro data, including 79.2% (19/24) of studies on PB MSCs and 75% (6/8) of studies on chondrogenic PB MPCs, confirmed the existence of PB MSCs and PB MPCs, respectively; all in vivo investigations showed that using PB as a cell source enhanced cartilage repair. PB MSCs were found in most of the animal studies (12/13), whereas 7 of 11 human studies described the presence of PB MSCs. This systematic review strongly indicates the existence of MSCs in the PB of animals, whereas the presence of MSCs in human PB is less clear. Although the presence of both MSCs and chondrogenic MPCs in the PB, as well as a few favorable outcomes associated with the use of PB-derived progenitors for cartilage repair in vivo, suggests that the PB is a potential alternative source of chondrogenic progenitor cells for cartilage repair, the efficacy of these cells has not been compared to those from other sources, such as bone marrow or adipose tissue in controlled studies. PMID- 27353076 TI - Bone Remodeling Around Implants with External Hexagon and Morse-Taper Connections: A Randomized, Controlled, Split-Mouth, Clinical Trial. AB - OBJECTIVES: To evaluate clinical, radiographic, microbiologic, and biomechanical parameters related to bone remodeling around implants with external hexagon (EH) and Morse-taper (MT) connections. MATERIALS AND METHODS: Twelve totally edentulous patients received four custom-made implants in the interforaminal region of the mandible. Two of those implants had the same macroscopic design, but different prosthetic connections. All patients received an immediate implant supported prosthesis. Clinical parameters (periimplant probing pocket depth (PPD), modified gingival index (mGI), and mucosal thickness (MTh)) were evaluated at 12 months follow-up. The distance between the top of the implant and the first bone-to-implant contact (IT-FBIC) was evaluated on standardized digital peri apical radiographs acquired at 1, 3, 6, and 12 months follow-up. Samples of the subgingival microbiota were collected 1, 3, and 6 months after implant loading and used for the quantification of Tanerella forsythia, Porphyromonas gingivalis, Aggragatibacter actinomycetemcomitans, Prevotella intermedia, and Fusobacterium nucleatum. Further, 36 computerized-tomography based finite element (FE) models were accomplished, simulating each patient under three loading conditions. RESULTS: The evaluated clinical parameters were equal for EH and MT implants. Mean IT-FBIC was significantly different between the tested connections (1.17 +/- 0.44 mm for EH, and 0.17 +/- 0.54 mm for MT, considering all evaluated time periods). No significant microbiological differences could be observed between tested connections. FE analysis showed a significantly higher peak of equivalent (EQV) strain (p = 0.005) for EH (mean 3,438.65 uepsilon) compared to MT (mean 840.98 uepsilon) connection. CONCLUSIONS: Radiographic periimplant bone loss depends on the implant connection type. MT connections showed less periimplant bone loss, compared to EH connections. PMID- 27353077 TI - A Case Report of Bilateral Sarcomatoid Carcinoma of Adrenal Glands With Adrenal Insufficiency. AB - Adrenocortical carcinomas are relatively rare, but they are considered to be highly aggressive malignant tumors. Sarcomatoid carcinomas represent an even more aggressive type. Bilateral malignant adrenal tumors are extraordinary rare, except for those that represent metastatic spread from a primary neoplasm. Here we report a case of a 69-year-old woman who presented symptoms that raised strong suspicions of adrenal insufficiency. Bilateral adrenal masses, identified in the imaging study, were responsible for the clinical manifestation and surgically resected. Surgical specimens of the bilateral adrenal tumors shared histological features compatible with sarcomatoid carcinoma. It was very difficult to confirm that the sarcomatoid carcinomas were derived from the cortex of the adrenal glands, but careful morphological observation and the panel of antibodies used for immunohistochemistry made the diagnosis possible. This is the first report of sarcomatoid carcinomas involving both adrenal glands. It should be emphasized that sarcomatoid carcinoma can arise bilaterally from even functionally impaired adrenal glands. PMID- 27353078 TI - High-Grade Neuroendocrine Carcinoma of the Breast With Focal Squamous Differentiation. AB - Primary neuroendocrine carcinoma of the breast is a rare tumor that comprises less than 1% of breast carcinomas, with most patients being in the sixth or seventh decade of their life. In this article, the authors present the case report of a 42-year-old woman with a rapidly growing tumor in her right breast. After clinical staging by physical examination, breast imaging, and thoracoabdominal computed tomography the patient underwent breast-conserving surgery. The histologic results showed a unique type of high-grade, predominantly large-cell neuroendocrine carcinoma with focal abrupt squamous differentiation. The authors also discuss the clinical and morphological characteristics of the tumor as well as treatment options. PMID- 27353079 TI - Muscle Activation During Peripheral Nerve Field Stimulation Occurs Due to Recruitment of Efferent Nerve Fibers, Not Direct Muscle Activation. AB - BACKGROUND: Peripheral nerve field stimulation (PNFS) is a potential treatment for chronic low-back pain. Pain relief using PNFS is dependent on activation of non-nociceptive Abeta-fibers. However, PNFS may also activate muscles, causing twitches and discomfort. In this study, we developed a mathematical model, to investigate the activation of sensory and motor nerves, as well as direct muscle fiber activation. METHODS: The extracellular field was estimated using a finite element model based on the geometry of CT scanned lumbar vertebrae. The electrode was modeled as being implanted to a depth of 10-15 mm. Three implant directions were modeled; horizontally, vertically, and diagonally. Both single electrode and "between-lead" stimulation between contralateral electrodes were modeled. The extracellular field was combined with models of sensory Abeta-nerves, motor neurons and muscle fibers to estimate their activation thresholds. RESULTS: The model showed that sensory Abeta fibers could be activated with thresholds down to 0.563 V, and the lowest threshold for motor nerve activation was 7.19 V using between-lead stimulation with the cathode located closest to the nerves. All thresholds for direct muscle activation were above 500 V. CONCLUSIONS: The results suggest that direct muscle activation does not occur during PNFS, and concomitant motor and sensory nerve fiber activation are only likely to occur when using between-lead configuration. Thus, it may be relevant to investigate the location of the innervation zone of the low-back muscles prior to electrode implantation to avoid muscle activation. PMID- 27353080 TI - Breast-feeding and malocclusions: The quality and level of evidence on the Internet for the public. AB - BACKGROUND: The authors sought to assess the quality of information on the Internet for laypeople regarding the effect of breast-feeding on malocclusions and to determine the levels of evidence of the articles cited to support the information. METHODS: The first author (E.J.D.) entered a key word term, "breast feeding and crooked teeth," and a natural language term, "does breast-feeding protect against crooked teeth," into 4 search engines. The author performed consecutive sampling of every Web site until 5 Web sites were identified that fulfilled the inclusion criteria per search engine, per search term, producing 40 Web sites for evaluation. The author assessed quality using the LIDA instrument and determined the levels of evidence of the cited articles according to the Joanna Briggs Institute Levels of Evidence. RESULTS: The author determined that the quality of the Web sites was moderate, represented by a median overall LIDA score of 73%. The author identified only 2 high-quality Web sites. Nearly one half of the Web sites cited a combined total of 10 scientific articles to support their content, and these ranged from moderate to very low levels of evidence. CONCLUSIONS: The authors found the quality of freely available information on the Internet for laypeople about the protective effect of breast-feeding against malocclusions to be moderate and that the evidence base cited to support the content ranged from moderate to very low levels of evidence. PRACTICAL IMPLICATIONS: Increasingly, patients are seeking health information online, although not all information is credible. Dental heath care practitioners should regularly review their practices' Web sites to ensure that they are accessible and that the content is usable, reliable, and up-to-date, particularly as new, higher-level evidence becomes available. PMID- 27353084 TI - A newly discovered member of the Atlastin family, BmAtlastin-n, has an antiviral effect against BmNPV in Bombyx mori. AB - Atlastin is a member of the dynamin protein superfamily and it can mediate homotypic fusion of endoplasmic reticulum (ER) membranes, which is required for many biological processes. In this study, a new Atlastin homologous protein, BmAtlastin-n, was characterized in silkworms and was found to contain an N terminal conserved GTPase domain and a coiled-coil middle domain. BmAtlastin-n is localized in the cytoplasm and enriched in silkworm midgut. Results also showed that overexpression of BmAtlastin-n in BmN-SWU1 cells could enhance resistance to BmNPV. To better confirm its antiviral effect, microRNA was used to knock down the expression of BmAtlastin-n in BmE-SWU1 cells with inducing the reproduction of BmNPV. A transgenic expression vector of BmAtlastin-n was constructed and introduced to silkworm embryos by microinjection. The transgenic silkworm also showed considerable antiviral capacity. In conclusion, these findings demonstrate that BmAtlastin-n plays an important role in BmNPV defense. More importantly, the current study may provide a new clue for Atlastin research. PMID- 27353085 TI - Ethanol extracts of chickpeas alter the total lipid content and expression levels of genes related to fatty acid metabolism in mouse 3T3-L1 adipocytes. AB - Desi-type chickpeas, which have long been used as a natural treatment for diabetes, have been reported to lower visceral adiposity, dyslipidemia and insulin resistance induced by a chronic high-fat diet in rats. In this study, in order to examine the effects of chickpeas of this type in an in vitro system, we used the 3T3-L1 mouse cell line, a subclone of Swiss 3T3 cells, which can differentiate into cells with an adipocyte-like phenotype, and we used ethanol extracts of chickpeas (ECP) instead of chickpeas. Treatment of the 3T3-L1 cells with ECP led to a decrease in the lipid content in the cells. The desaturation index, defined as monounsaturated fatty acids (MUFAs)/saturated fatty acids (SFAs), was also decreased by ECP due to an increase in the cellular content of SFAs and a decrease in the content of MUFAs. The decrease in this index may reflect a decreased reaction from SFA to MUFA, which is essential for fat storage. To confirm this hypothesis, we conducted a western blot analysis, which revealed a reduction in the amount of stearoyl-CoA desaturase 1 (SCD1), a key enzyme catalyzing the reaction from SFA to MUFA. We observed simultaneous inactivations of enzymes participating in lipogenesis, i.e., liver kinase B1 (LKB1), acetyl-CoA carboxylase (ACC) and AMPK, by phosphorylation, which may lead to the suppression of reactions from acetyl-CoA to SFA via malonyl-CoA in lipogenesis. We also investigated whether lipolysis is affected by ECP. The amount of carnitine palmitoyltransferase 1 (CPT1), an enzyme important for the oxidation of fatty acids, was increased by ECP treatment. ECP also led to an increase in uncoupling protein 2 (UCP2), reported as a key protein for the oxidation of fatty acids. All of these results obtained regarding lipogenesis and fatty acid metabolism in our in vitro system are consistent with the results previously shown in rats. We also examined the effects on SCD1 and lipid contents of ethanol extracts of Kabuli-type chickpeas, which are used worldwide. The effects were similar, but of much lesser magnitude compared to those of ECP described above. Thus, Desi-type chickpeas may prove to be effective for the treatment of diabetes, as they can alter the lipid content, thus reducing fat storage. PMID- 27353087 TI - Human LAT mutation results in immune deficiency and autoimmunity but also raises questions about signaling pathways. PMID- 27353088 TI - Combination immunotherapy for cancer. PMID- 27353086 TI - MLP and CARP are linked to chronic PKCalpha signalling in dilated cardiomyopathy. AB - MLP (muscle LIM protein)-deficient mice count among the first mouse models for dilated cardiomyopathy (DCM), yet the exact role of MLP in cardiac signalling processes is still enigmatic. Elevated PKCalpha signalling activity is known to be an important contributor to heart failure. Here we show that MLP directly inhibits the activity of PKCalpha. In end-stage DCM, PKCalpha is concentrated at the intercalated disc of cardiomyocytes, where it is sequestered by the adaptor protein CARP in a multiprotein complex together with PLCbeta1. In mice deficient for both MLP and CARP the chronic PKCalpha signalling chain at the intercalated disc is broken and they remain healthy. Our results suggest that the main role of MLP in heart lies in the direct inhibition of PKCalpha and that chronic uninhibited PKCalpha activity at the intercalated disc in the absence of functional MLP leads to heart failure. PMID- 27353090 TI - Development and implementation in the Monte Carlo code PENELOPE of a new virtual source model for radiotherapy photon beams and portal image calculation. AB - This work aims at developing a generic virtual source model (VSM) preserving all existing correlations between variables stored in a Monte Carlo pre-computed phase space (PS) file, for dose calculation and high-resolution portal image prediction. The reference PS file was calculated using the PENELOPE code, after the flattening filter (FF) of an Elekta Synergy 6 MV photon beam. Each particle was represented in a mobile coordinate system by its radial position (r s ) in the PS plane, its energy (E), and its polar and azimuthal angles (phi d and theta d ), describing the particle deviation compared to its initial direction after bremsstrahlung, and the deviation orientation. Three sub-sources were created by sorting out particles according to their last interaction location (target, primary collimator or FF). For each sub-source, 4D correlated-histograms were built by storing E, r s , phi d and theta d values. Five different adaptive binning schemes were studied to construct 4D histograms of the VSMs, to ensure histogram efficient handling as well as an accurate reproduction of E, r s , phi d and theta d distribution details. The five resulting VSMs were then implemented in PENELOPE. Their accuracy was first assessed in the PS plane, by comparing E, r s , phi d and theta d distributions with those obtained from the reference PS file. Second, dose distributions computed in water, using the VSMs and the reference PS file located below the FF, and also after collimation in both water and heterogeneous phantom, were compared using a 1.5%-0 mm and a 2%-0 mm global gamma index, respectively. Finally, portal images were calculated without and with phantoms in the beam. The model was then evaluated using a 1%-0 mm global gamma index. Performance of a mono-source VSM was also investigated and led, as with the multi-source model, to excellent results when combined with an adaptive binning scheme. PMID- 27353091 TI - [New progression of translational research on colorectal cancer]. AB - Precision medicine is becoming the goal of translational research on colorectal cancer. Accurate molecular subtyping contributes to better guidance of clinical practice. The current TNM staging system of colorectal cancer is inadequate in terms of guiding clinical practice, such as the underestimation of prognosis of with stage II( and III( colorectal cancer TNM staging, and identification of high risk and low-risk patients with stage II( colorectal cancer. Researchers from Europe and US have proposed a number of molecular subtypings with clinicopathological phenotypes and molecular phenotypes, which has certain practical significance and is beneficial to the choice of treatment regimen and targeted drugs. But the current results of subtyping research require further validations by clinical large scale multi-center trials. Based on precision medicine, molecular subtyping gradually reveals its clinical significance and is optimized through combining genomics with various clinical phenotypes, indicating its guidance for clinical practice, which is the inevitable course of precision medicine accomplishment. In recent years, there have been many new advances in colorectal cancer liver metastasis treatment. The prognosis of colorectal cancer patients undergoing resection of liver metastasis lesion is similar to those with stage III(. Early recurrence within 6 months after translational treatment and resection occurred in about one third of the patients with initially unresectable liver metastasis, and the overall survival was poor. Thus, an evaluation system should be established in order to avoid the strong therapy and strive for better quality of life in some patients. Individualized treatment for colorectal cancer is emphasized increasingly. Body fluid (peripheral blood and urine) marker detection is a recent research hotspot, including serum protein(polypeptide), plasma miRNA, circulating tumor cells and circulating nucleic acid. PMID- 27353089 TI - Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction. AB - Acute myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Inflammatory cells orchestrate postischemic cardiac remodeling after MI. Studies using mice with defective mast/stem cell growth factor receptor c-Kit have suggested key roles for mast cells (MCs) in postischemic cardiac remodeling. Because c-Kit mutations affect multiple cell types of both immune and nonimmune origin, we addressed the impact of MCs on cardiac function after MI, using the c-Kit-independent MC-deficient (Cpa3(Cre/+)) mice. In response to MI, MC progenitors originated primarily from white adipose tissue, infiltrated the heart, and differentiated into mature MCs. MC deficiency led to reduced postischemic cardiac function and depressed cardiomyocyte contractility caused by myofilament Ca(2+) desensitization. This effect correlated with increased protein kinase A (PKA) activity and hyperphosphorylation of its targets, troponin I and myosin-binding protein C. MC specific tryptase was identified to regulate PKA activity in cardiomyocytes via protease-activated receptor 2 proteolysis. This work reveals a novel function for cardiac MCs modulating cardiomyocyte contractility via alteration of PKA regulated force-Ca(2+) interactions in response to MI. Identification of this MC cardiomyocyte cross-talk provides new insights on the cellular and molecular mechanisms regulating the cardiac contractile machinery and a novel platform for therapeutically addressable regulators. PMID- 27353092 TI - [Present status and future of multi-disciplinary treatment for colorectal cancer]. AB - Multi-disciplinary treatment (MDT) is an effective pattern to implement the standardized and individualized treatment for cancer. Under the pattern of MDT which integrates the surgery, chemotherapy, radiotherapy, interventional therapy, targeted therapy and immune therapy, there has been a landmark progress in the diagnosis and treatment of colorectal cancer. Curative resection followed by adjuvant chemotherapy has been established as a standard treatment for stage III( colon cancer, but it is still controversial about whether patients with stage II( colon cancer should receive adjuvant chemotherapy and which regimen is preferred. Decision making regarding the use of adjuvant therapy for stage II( patients should not only depend upon the clinicopathological features but also individualized discussion between patients and physicians about the biological behavior of the disease, evidence supporting the efficacy, and possible toxicity. Radical operation following neoadjuvant chemoradiotherapy is currently the standard modality for locally advanced rectal cancer, but the strategy of 'Wait and See' is proposed by some researchers for those achieving complete response after chemoradiotherapy, although there is no sufficient supportive data yet. Patients with metastatic colorectal cancer should undergo an upfront evaluation and discussion by a multidisciplinary team before the initial treatment. Achieving a negative surgical margin with adequate remanent liver reserve is the criteria for determining the resectability of liver metastasis. Both adjuvant and neoadjuvant chemotherapy are two alternatives for initially resectable liver metastasis. Concomitant with the progress of medicine, the MDT is moving toward a precise treatment system oriented by genes and being able to predict the prognosis, efficacy and side effects exactly. PMID- 27353093 TI - [Research hotspot and progress of preoperative chemoradiotherapy for rectal cancer]. AB - Preoperative chemoradiotherapy (CRT) has become an important component of comprehensive treatment for rectal cancer. Although local recurrent risk has been remarkably reduced by CRT, distant metastasis remains the main cause of therapeutic failure. Therefore, more and more studies focused on controlling distant metastasis in order to prolong long-term survival. Recently, CRT has achieved certain progression in rectal cancer: (1)Patients with stage T3 should be classified into specific subgroups to formulate individualized treatment regimen. For stage T3a, it is feasible to perform surgery alone or administrate low intensity preoperative CRT; for stage T3b and T3c, conventional preoperative CRT should be performed in order to reduce the risk of recurrence postoperatively. (2)With regard to combined regimen for chemotherapy, oral capecitabine superiors to intravenous bolus 5-fluorouracil (5-FU) and is comparable to continuous intravenous infusion 5-FU with a better safety. Therefore, capecitabine is recommended for older patients and those with poor tolerance to chemotherapy. Compared to single 5-FU concurrent CRT, addition of oxaliplatin into preoperative CRT may result in a higher survival benefit in Chinese patients. As to the application of irinotecan, bevacizumab or cetuximab, unless there are more evidence to confirm their efficacy and safety from randomized controlled trial, they should not be recommended for adding to preoperative CRT routinely. (3)On the optimization in CRT pattern, the application values of induction chemotherapy before concurrent CRT, consolidation chemotherapy after concurrent CRT, neoadjuvant sandwich CRT, neoadjuvant chemotherapy alone and short-course preoperative radiotherapy remain further exploration. (4)On the treatment strategy for clinical complete response (cCR) after CRT, whether "wait and see" strategy is able to be adopted, it is still a hot topic with controversy. PMID- 27353094 TI - [Radiotherapy standard and progress in locally advanced rectal cancer]. AB - Recently, treatment strategy optimization for neoadjuvant therapy of rectal cancer includes two aspects: (1) Increasing treatment intensity may improve pathological complete response rate, including increasing radiation dose or concurrent chemotherapy intensity, or shifting adjuvant chemotherapy; (2) Short course radiotherapy or neoadjuvant chemotherapy which can promise treatment efficacy will decrease toxicity and lead to better tolerance. Long-course chemoradiotherapy is the recent treatment standard for locally advanced rectal cancer. NCCN guidelines do not recommend combined chemotherapy in the radiotherapy period. However, it is important for individualized treatment of rectal cancer if appropriate patients who may benefit from the combined concurrent chemotherapy can be selected. Short-course radiotherapy is defined as 5 Gy * 5. It is recommended for T3 or N+ rectal cancer in NCCN guidelines, but not for T4 patients. In ESMO guidelines, stratified patients of intermediate risk by MRI can be treated with either short-course or long-course radiotherapy, but short-course radiotherapy is not recommended for T4 or positive mesorectum fascia (MRF+) patients with high risk. Neoadjuvant chemotherapy incorporated in the neoadjuvant part has been a therapeutic choice in NCCN guidelines. However, It is still unclear whether chemotherapy upfront as a component of neoadjuvant treatment or even completion of chemotherapy before surgery can improve treatment outcome or not. There are phase II( studies focused on this issue and final results are pending. PMID- 27353095 TI - [Advances of minimally invasive technique in colorectal cancer surgery]. AB - Colorectal surgery is rapidly developing in the direction of minimally invasive surgery and functional surgery. New technology and ideas are constantly emerging recently. Laparoscopic colon surgery has already been recommended by NCCN guideline. However, laparoscopic rectal cancer surgery still needs to wait for survival and recurrence rates of long-term follow-up data for verification. In recent years, with the rapid progression of imaging equipment of laparoscope, the new 3D laparoscopic system will process image more quickly, and surgeons can get space depth feeling like open surgery only with a pair of glasses. The new 3D laparoscopic system has many advantages, and can also shorten the learning curve of the beginners. But it does not mean the traditional 2D laparoscopy has been out of date. It is admitted that dialectical view on the development of the technology and equipment is still required. New things also need the accumulation of time and validation, and the deficiency of imaging system remains to be improved. At present, the robotic colorectal cancer surgery is still in its infancy, and its application is relatively common in colon surgery. In respect of robotic rectal cancer surgery, it still lacks of long-term follow-up survival results for verification. To reduce physical and psychological trauma for patients is the goal of the surgeon. Surgeons are experiencing the change from minimally invasion to non-invasion. Natural orifice translumenal endoscopic surgery (NOTES) and natural orifice specimen extraction surgery (NOSES) arise at the historic moment. Among them, transanal total mesorectal excision (taTME) incorporates the concepts of NOTES, anal minimally invasive surgery and total mesorectum excision, guaranteeing the radical cure and no scar of abdomen, but it still needs multicenter, large sample and long-term follow-up clinical data to prove its safety, efficacy and indication. Therefore, surgical procedure is transforming from conventional laparoscopic surgery to the NOTES and NOSES. The surgical principle is the eternal cornerstone to ensure the radical tumor resection and the safety of patients. PMID- 27353096 TI - [Prevention of intraoperative incidental injuries during sphincter-preserving surgery for rectal cancer and management of postoperative complication]. AB - Prevention of intraoperative incidental injuries during radical operation for rectal cancer and management of postoperative complication are associated with successful operation and prognosis of patients. This paper discusses how to prevent such intraoperative incidental injuries and how to manage postoperative complication. (1) Accurate clinical evaluation should be performed before operation and reasonable treatment decision should be made, including determination of the distance from transection to lower margin of the tumor, T and M staging evaluated by MRI, fascia invasion of mesorectum, metastasis of lateral lymph nodes, metastatic station of mesentery lymph node, association between levator ani muscle and anal sphincter, course and length of sigmoid observed by Barium enema, length assessment of pull-through bowel. Meanwhile individual factors of patients and tumors must be realized accurately. (2) Injury of pelvic visceral fascia should be avoided during operation. Negative low and circumference cutting edge must be ensured. Blood supply and adequate length of pull-down bowel must be also ensured. Urinary system injury, pelvic bleeding and intestinal damage should be avoided. Team cooperation and anesthesia procedure should be emphasized. Capacity of handling accident events should be cultivated for the team. (3) intraoperative incidental injuries during operation by instruments should be avoided, such as poor clarity of camera due to spray and smog, ineffective instruments resulted from repeated usage. (4) As to the prevention and management of postoperative complication of rectal cancer operation, prophylactic stoma should be regularly performed for rectal cancer patients undergoing anterior resection, while drainage tube placement does not decrease the morbidities of anastomosis and other complications. After sphincter preserving surgery for rectal cancer, attentions must be paid to the occurrence of anastomotic bleeding, pelvic bleeding, anastomotic fistula, ileus, intestinal necrosis and anastomotic stenosis. After sphincter-preserving surgery for rectal cancer, if small amount of bleeding happens, titanium clamp or electric coagulation can be used; if delayed pelvic bleeding occurs obviously, embolism should be applied. Conservative treatment may be used for the non-carcinomatous ileus. When small anastomotic stenosis is found, local treatment is available (finger dilation, balloon expansion, transanal radiated cutting or resection), and for severe stenosis, transadominal operation is required. PMID- 27353097 TI - [Assessment of lymph node status in rectal cancer by imaging]. AB - Assessment of lymph node status in patients with rectal cancer is important before operation and neoadjuvant treatment because it has an influence on definition of operative plan, strategy of chemoradiotherapy and prognosis of the patients with rectal cancer. The imaging modalities that can be used to assess lymph node status include magnetic resonance imaging (MRI), endorectal ultrasonography (ERUS), multi-row detector computer tomography (MDCT), and PET CT. The existing imaging criteria for metastatic lymph nodes in rectal cancer have not been reached. Combined with morphologic and functional imaging characteristics can be accurately predict metastatic lymph nodes. Based on the size of lymph node, the accuracy of rectal cancer N stage defined by imaging modality is poor. If the border and signal intensity of lymph nodes are used to predict the metastasis, the sensitivity and specificity can be significantly improved. However, the reproducibility needs an improvement because of limitation in imaging quality and difference in ability of imaging interpretation. In comparison, ultra small superparamagnetic iron oxide MRI (USPIO-MRI) has relatively higher reproducibility in definition of the metastatic lymph nodes while it is not permitted as an imaging tool used in clinical practice. In addition, USPIO-MRI has been used to evaluate the lymph node response to chemotherapy. As functional imaging tool, DW-MRI has high sensitivity in detection of lymph nodes, while the specificity is low. In contrast, PET-CT has lower sensitivity because of the limitation in imaging resolution, which can not find the small metastatic lymph nodes. ERUS and high resolution MRI have similar ability in distinguishing metastatic and benign nodes within mesorectum. While MRI and DW-MRI have greater diagnostic view than ERUS, thus they can effectively screen and diagnose the pelvic lateral lymph nodes and rectal upper arteriovenous lymph nodes. MDCT is the better choice in screening chest and abdominal metastatic lymph nodes compared with other modalities. The proper selection of imaging modality or combination of multi-modalities is necessary for special purpose in clinical practice. PMID- 27353098 TI - [Efficacy analysis of suprapubic single-incision laparoscopy in the treatment of rectosigmoid cancer]. AB - OBJECTIVE: To evaluate the efficacy and cosmetic result of suprapubic single incision laparoscopic surgery(SSILS) in the treatment of rectosigmoid cancer. METHODS: Clinicopathological data of 16 patients undergoing SSILS and 122 undergoing conventional laparoscopic surgery(CLS) for sigmoid colon and upper rectal cancer in the Nanfang Hospital from August 2011 to July 2012 were retrospectively analyzed. The patients were analyzed with propensity score matching at a ratio of 1 to 2 by logistic regression analysis. The matching covariates included age, gender, body mass index, American Society of Anesthesiologists(ASA) score, tumor location, tumor diameter, pathologic TNM stage, previous abdominal surgery. After matching, 48 patients (16 SSILS and 32 CLS) were enrolled in the study. The SSILS group comprised of 13 (81.3%) males with mean age of (56.4+/-13.4) years. The CLS group comprised of 23(71.9%) males with mean age of (55.6+/-13.7) years. Postoperative short-term parameters, oncologic efficacy and cosmetic result were compared between the two groups. RESULTS: The male gender ratio, age, body mass index, ASA score, tumor location, tumor diameter, tumor differentiation, depth of invasion, lymph node metastasis, TNM stage, previous abdominal surgery were comparable between the two groups. As compared to CLS group, less incision length [(4.8+/-1.5) cm vs. (6.8+/-1.2) cm, U=63.000, P=0.000], shorter time to ambulation [(2.6+/-1.0) days vs. (3.9+/-1.5) days, U=116.500, P=0.002], shorter hospital stay [(8.4+/-5.3) days vs.(9.2+/-3.1) days, U=139.000, P=0.010] and less postopertive pain(Visual Analogue Scale: 4.3+/ 1.4 vs. 5.2+/-1.1 at day 3, t=2.457, P=0.018; 3.7+/-1.0 vs. 4.6+/-1.0 at day 4, t=2.700, P=0.010; 3.3+/-0.8 vs. 4.0+/-1.0 at day 5, t=2.466, P=0.017) were observed in SSILS group. The other short-term parameters(blood loss, operative time, insertion of additional port rate, time to flatus, defecation, time to liquid and soft diet, complication morbidity, number of lymph nodes harvested, proximal and distal resection margin) were not significantly different between 2 groups(all P>0.05). The median follow-up time was 41(22-49) months. There was no loco-regional recurrence in 2 groups. Distant metastasis was 18.8% (n=3, all liver metastasis) and 6.3% (n=2, one liver metastasis and one peritoneal metastasis) in SSILS and CLS groups (chi(2)=0.698, P=0.404) respectively. Three year disease-free survival and 3-year overall survival were 81.3% vs 93.0%(chi(2)=1.355, P=0.244) and 100.0% vs 96.9%(chi(2)=0.500, P=0.480) in SSILS and CLS groups, respectively. Photograph questionnaire investigation showed that the cosmetic score was significantly higher in SSILS group than that in CLS group (8.9+/-1.1 vs. 7.6+/-1.1, U=100.500, P=0.000). Of 48 patients of 2 groups, 81.3%(39/48) case preferred SSILS. CONCLUSION: In experienced laparoscopic treatment centers, SSILS for rectosigmoid cancer is feasible and safe with quite good oncological efficacy and certain advantages, such as fast recovery, less pain and better cosmetic result. PMID- 27353099 TI - [Laparoscopy combined with transperineal extralevator abdominoperineal excision for locally advanced low rectal cancer]. AB - OBJECTIVE: To evaluate the laparoscopy combined with transperineal extralevator abdominoperineal excision (TP-ELAPE) for locally advanced low rectal caner. METHODS: Clinical data of 12 patients with locally advanced low rectal cancer undergoing laparoscopy combined with TP-ELAPE in our department from May 2013 to March 2015 were retrospectively analyzed. There were 8 male and 4 female patients with median aged of 63 (46 to 72) years. The median distance from tumor lower margin to anal verge was 3.5(2.0 to 4.0) cm. A self-made transanal suit for minimally invasive operation was used to make a sealed lacuna outside the sphincter, thus laparoscope can be applied to perform transperineal operation. RESULTS: All the patients underwent operations successfully without conversion to open abdominal operation. The median operating time was 206 (180 to 280) minutes with perineal operating time 95(80 to 120) minutes. The median intraoperative blood loss was 120(50 to 200) ml. The median postoperative hospital stay was 12(9 to 18 ) days. Postoperative pathology revealed that all circumferential margins (CRM) were negative. The area of sample horizontal section was (2 824+/-463) mm(2), and of outer muscularis propria was(2 190+/-476) mm(2). Postoperative complications included chronic sacrococcygeal region pain in 2 cases, urinary retention in 3 cases, perineal wound infection in 1 case. No perineal seroma, perineal hernia, wound dehiscence and sinus tract formation were observed. Among 8 patients with preoperative normal sexual function, sexual dysfunction occurred in 2 patients. There was no local recurrence and metastasis during a median follow-up of 21(12 to 34) months. CONCLUSION: Laparoscopy combined with TP-ELAPE has the potential to simplify the operation procedure for low rectal cancer, can ensure the radical treatment and safety of operation, and may be carried out in experienced centers. PMID- 27353100 TI - [Clinical analysis on lymph node metastasis pattern in left-sided colon cancers]. AB - OBJECTIVE: To investigate the pattern of lymph node metastasis in patients with left-sided colon cancer in order to provide evidences for the choice of operation mode and the range of lymph node clearance. METHODS: Clinical data of 556 cases with left-sided colon carcinoma undergoing surgical treatment in Department of Colorectal Surgery, Fujian Medical University Union Hospital from January 2000 to October 2014 were retrospectively analyzed. Among these patients, cancer of splenic flexure and transverse colon close to splenic flexure (splenic flexure group) was found in 41 cases, descending colon cancer in 73 cases(descending colon goup) and sigmoid colon cancer in 442 cases (sigmoid colon group), respectively; T1 was found in 29 cases, T2 in 63 cases, T3 in 273 cases, T4 in 191 cases. All the patients underwent D3 radical operation or complete mesocolic excision(CME). Para-bowel lymph node was defined as the first station, mesenteric lymph node as the second station, and lymph node in root of mesentery and around upper and inferior mesenteric arteries as the third station. Metastasis was compared among these 3 stations with regard to different sites and tumor invasions. RESULTS: The total lymph node metastasis rate was 49.6%(276/556). The lymph node metastasis rates of splenic flexure, descending colon and sigmoid colon groups were 53.7%(22/41), 52.1%(38/73) and 48.9%(216/442) respectively without significant difference (P>0.05). The lymph node metastasis rates of the first, second, and third stations were 47.3%(263/556), 16.9%(94/556) and 5.8%(32/556) respectively with significant difference (chi(2)=287.54, P=0.000). In the first, second and third station, the lymph node metastasis rate was 13.8%(4/29), 0 and 0 in T1; 25.4%(16/63), 4.8%(3/63) and 3.2%(2/63) in T2; 45.8%(125/273), 14.7%(40/273) and 4.8%(13/273) in T3; 61.8%(118/191), 26.7%(25/191) and 8.9%(17/191) in T4 respectively. In splenic flexure group, metastasis rates were similar between No.222 and No.232[14.6%(61/41) vs. 12.2%(5/41), chi(2)=0.11, P=1.000] and between No.223 and No.253 [7.3% (3/41) vs. 2.4% (1/41), chi(2)=1.05, P=0.616]. In descending colon group, metastasis rate of No.232 was higher as compared to No.222[15.1%(11/73) vs. 2.7% (2/73), chi(2)=6.84, P=0.017]; metastasis rate of No.253 was slightly higher as compared to No.223 without significant difference [4.1%(3/73) vs. 0, chi(2)=3.06, P=0.245]. Metastasis rates of No.222 and No.223 in splenic flexure group were significantly higher than those in descending colon and sigmoid colon groups (chi(2)=5.69, P=0.025; Fisher exact test, P=0.044); While such rates of No.232(No.242 for sigmoid colon group) and No.253 were not significantly different among 3 groups respectively (chi(2)=0.90, P=0.660; chi(2)=1.14, P=0.611). CONCLUSIONS: Left-sided colon cancers in T1 should undergo D2 radical operation, while cancers in T2 to T4 should undergo D3 radical operation. The D3 radical operation for splenic flexure cancers and cancers of transverse colon close to splenic flexure should clear No.223 and No.253. The D3 radical operation for descending colon cancer should clear No.222 and No.253. The D3 radical operation for sigmoid colon should clear No.253. PMID- 27353101 TI - [Clinical study on locally advanced rectal cancer patients with pathological complete response after neoadjuvant chemoradiotherapy]. AB - OBJECTIVE: To explore the efficacy prediction of the locally advanced rectal cancer patients, especially those with pathological complete response(pCR), receiving neoadjuvant chemoradiotherapy in order to execute precise preoperative neoadjuvant chemoradiotherapy. METHODS: From January 2000 to January 2011, 125 patients diagnosed as locally advanced rectal cancer receiving preoperative neoadjuvant chemoradiotherapy in our department with complete data were enrolled in this study, including 85 males and 40 females with mean age of 54(15 to 77) years old. All the patients received radiotherapy with 46 Gy(23 times) and administered XELOX regimen (oxaliplatin 100 mg/m(2) plus capecitabine 2 000 mg/m(2)) for 2 courses simultaneously, and underwent radical operation 6 to 8 weeks after chemoradiotherapy. The data of these patients were analyzed retrospectively. Pathological remission was divided into 4 grades. Patients achieving grade 4 were defined as pCR, and those achieving above grade 2 were defined as better response. Logistic regression analysis was used to identify significant predictors of pCR. RESULTS: Among 125 patients, 16(12.8%) achieved pCR status, and 90(72.0%) had better response to the neoadjuvant chemoradiotherapy. Logistic regression analysis showed that age(OR:1.060, P=0.037) and preoperative positive lymph nodes detected by endorectal ultrasonography (OR:0.059, P=0.006) were independent predictors of pCR after neoadjuvant chemoradiotherapy. CONCLUSIONS: Preoperative existence of lymph node metastasis around bowel indicates the poor response to neoadjuvant chemoradiotherapy. Age is associated with pCR in patients receiving neoadjuvant chemoradiotherapy. PMID- 27353102 TI - [Diagnostic value of 3.0-tesla high-resolution magnetic resonance imaging for invasion depth of rectal cancer]. AB - OBJECTIVE: To evaluate the accuracy of 3.0T high-resolution magnetic resonance imaging(MRI) in definition of tumor invasion depth staging (T staging) before operation. METHODS: Clinical and radiographic data of 49 rectal cancer patients who underwent radical resection within two weeks after 3.0 T high-resolution MRI examination without preoperative neoadjuvant chemotherapy in Peking University People's Hospital between February 2015 and November 2015 were retrospectively collected. Two radiologists reviewed the MRI imagines and evaluated the location and T staging of rectal cancer independently(radiologist A and B). The kappa statistics was used to evaluate the interobserver agreement, and kappa value greater than 0.81 indicated excellent agreement. The accuracy, sensitivity and specificity of high-resolution MRI in definition of rectal cancer T staging were assessed with pathological result as golden standard. RESULTS: According to pathological result of 49 rectal cancer patients, 3 were pT1, 17 were pT2, 22 were pT3, and 7 were pT4a. In 2 cases of mucinous adenocarcinoma, MRI T2WI showed focal or diffuse significantly higher signal close to perirectal fat. And in other 47 patients of non-mucinous adenocarcinoma, MRI T2WI showed equal or higher signal compared with pelvic muscle. Interobserver agreement was excellent in diagnosis of T staging of rectal cancer with 3.0T high-resolution MRI(Kappa=0.87). The accuracy, sensitivity and specificity of both radiologists for T1 staging was 95.9%(47/49), 1/3 and 100%(46/46) respectively, besides, 1 case was both diagnosed correctly and 2 cases were overstaged. For 2 radiologists, the accuracy of T2 staging was 87.8%(43/49) and 91.8%(45/49) respectively, the sensitivity was both 88.2%(15/17), and the specificity was 87.5%(28/32) and 93.5%(30/32) respectively, besides, 15 cases were both diagnosed correctly and 2 cases were overstaged. The accuracy for T3 staging was 89.8%(44/49) and 93.9%(46/49) respectively, the sensitivity was 86.4%(19/22) and 95.5%(21/22) respectively, and the specificity was both 92.6%(25/27). Radiologist A made correct diagnosis for 19 cases, understaged 2 cases and overstaged 1 case. Radiologist B made correct diagnosis for 21 cases and only overstaged 1 case. The accuracy, sensitivity and specificity of both radiologists for T4a staging was 98.0%(48/49), 7/7 and 97.6%(41/42) respectively, besides, 7 cases were both diagnosed correctly. The overall accuracy of T staging was 85.7%(42/49) and 89.8%(44/49) by two radiologists respectively. The accuracy for differentiating T1/T2 from T3/T4 was 91.8%(45/49) and 95.9%(47/49) by two radiologists respectively. Radiologist A overstaged 2 cases and understaged 2 cases, and radiologist B overstaged 2 cases. CONCLUSION: High-resolution MRI can accurately evaluate preoperative T staging of rectal cancer and help select the high-risk rectal cancer patients with over T3 to receive neoadjuvant treatment. PMID- 27353103 TI - [Association of colorectal adenoma and metabolic syndrome and relevant parameters]. AB - OBJECTIVE: To evaluate the association of colorectal adenoma with metabolic syndrome (MS) and relevant parameters. METHODS: Clinical data of 289 subjects who underwent screening colonoscopy in the University of Hong Kong-Shenzhen Hospital from January 2014 to June 2015 were retrospectively analyzed, including 130 normal subjects (normal group) and 159 cases with colorectal adenoma confirmed by pathology(adenoma group). Levels of MS-associated parameters were compared between the two groups, and the association of metabolic diseases with colorectal adenoma was examined. RESULTS: The gender, smoking and drinking habit, regular physical activity, family history of colorectal cancer, and consumption history of long-term non-steroidal anti-inflammatory drugs were not significantly different between two groups (all P>0.05). As compared to normal group, adenoma group had higher body mass index (BMI) [(23.5+/-3.2) kg/m(2) vs. (22.7+/-2.8) kg/m(2), t=1.97, P=0.050], larger abdominal circumference [(83.4+/-10.3) cm vs. (79.6+/-13.8) cm, t=2.46, P=0.015], higher serum high-density lipoprotein level [(1.3+/-0.3) mmol/L vs. (1.2+/-0.3) mmol/L, t=2.03, P=0.044], and higher serum cholesterol [(5.4+/-1.0) mmol/L vs. (5.0+/-1.1) mmol/L, t=2.39, P=0.018]. No significant difference was demonstrated in comparing hip circumference and waist hip ratio, as well as serum fasting glucose and triglyceride(all P>0.05). Higher incidence of colorectal adenoma was found in subjects with MS [69.8%(37/53) vs. 1.7%(122/236), P=0.017], overweight or obesity [65.1% (56/86) vs. 50.7%(103/203), P=0.025], hypertension [67.3%(37/55) vs. 52.1%(122/234), P=0.046] and hypercholesterolemia [66.7%(64/96) vs. 49.2%(95/193), P=0.005]. CONCLUSIONS: Metabolic syndrome increased the risk of developing colorectal adenoma. The mechanism may be related to higher serum cholesterol and high density lipoprotein, which may lead to the elevated catabolism of serum cholesterol. Screening colonoscopy should be performed for patients diagnosed as metabolic syndrome, especially for those with central obesity and hypercholesterolemia, thus early diagnosis and treatment of colorectal adenoma may be available. PMID- 27353104 TI - [Application of a novel method to collect large amount of fecal mucosa in screening colorectal cancer]. AB - OBJECTIVE: To explore the application of a novel device of collecting large amount of fecal mucosa for detecting the DNA methylation and screening colorectal cancer. METHODS: Preoperative complete fecal sample and surgical specimen of 10 patients with colorectal cancer, and complete fecal sample and normal bowel mucosal samples confirmed by colonoscopy of 6 hospitalization cases at The Third Affiliated Hospital, Nanjing University of TCM from March to April 2014 were collected. A self-made bowel mucosa collector (consisting of upper, middle, lower three containers of 1 000 ml volume, with filter screen in each bottom whose pore diameter is 100, 200 and 300 mesh.) was used to collect mucosal exfoliation cells. Fecal DNA kit was applied to extract DNA of exfoliation cells and the concentration and purity of DNA were measured by UV spectrophotometer (A260/A280), meanwhile DNA methylation of fecal fluid and mucosal tissues was detected by bisulfite sequencing pCR(BSP). RESULTS: DNA methylation sequencing showed that FBN1, SPG20, and SNCA genes presented methylation in CpG island in fecal fluid and cancer tissues from 10 colorectal cancer patients, but did not presented methylation in fecal fluid and mucosa from 6 control cases. When fecal amount was below 100 g, collection rate of fecal fluid was 60% to 80%; when fecal amount was over 100 g, collection rate of fecal fluid was unstable. When fecal amount was 50 to 100 g, DNA A260/A280 value was 1.6 to 1.8, and DNA concentration was 5.0 to 56.1 ng/L. CONCLUSION: Collection rate of fecal fluid with this self made fecal mucosa collector is quite stable when managing fecal amount of 50 to 100 g once, and can obtain higher purity and concentration of DNA, meeting the demand of methylation detection for screening colorectal cancer. PMID- 27353105 TI - [Expression of NF-E1b in colorectal cancer tissues and its clinical significance]. AB - OBJECTIVE: To explore the expression of NF-E1b in colorectal cancer tissues and its association with various clinicopathological parameters and prognosis of the patients. METHODS: Clinicopathological and follow-up data of 168 colorectal cancer patients undergoing radical operation at Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute from 2005 to 2012 were retrospectively analyzed, including 96 males and 72 females, with mean age of (57.8+/-11.2) years. The expression of NF-E1b protein was detected in samples of 168 resected colorectal cancer tissues and 45 adjacent non-cancerous tissues by immunohistochemistry. The expression rates of NF-E1b were compared among different clinicopathological features. Moreover, the association between NF-E1b expression and prognosis was analyzed. RESULTS: The expression of NF-E1b protein located mainly in cytoplasm. Positive rate of NF-E1b expression in adjacent non cancerous tissues was 17.8% (8/45), which was obviously lower than 67.9%(114/168) of cancer tissues with significant difference (chi(2)=36.376, P=0.000). Clinicopathological parameters analysis suggested that the expression level of NF E1b in cancer tissues was associated with age (chi(2)=4.862, P=0.030), TNM staging (chi(2)=10.969, P=0.002), lymph node metastasis (chi(2)=7.390, P=0.008) and distal metastasis (chi(2)=17.887, P=0.000). The median follow-up time was 23(1-77) months. The overall 5-year survival of this cohort was 33.3%. Colorectal cancer patients with high levels of NF-E1b expression showed a worse overall survival compared with those with low levels of NF-E1b expression (18.4% vs. 56.6%, P=0.000). Univariate Cox regression analysis showed that tumor location (P=0.034), tumor size (P=0.003), TNM staging (P=0.000), depth of tumor invasion (P=0.009), lymph node metastasis (P=0.000), distant metastasis (P=0.000) and NF E1b expression level (P=0.001) were associated with the prognosis of colorectal cancer patients. Multivariate Cox regression analysis revealed that tumor diameter >4 cm (HR=2.193,95% CI:1.334 to 3.603, P=0.002), distant metastasis (HR=2.064, 95% CI:1.160 to 3.672, P=0.014) and high NF-E1b expression (HR=1.994,95% CI:1.068 to 3.724, P=0.030) were independent risk factors of predicting poor prognosis of colorectal cancer patients. CONCLUSIONS: NF-E1b expression up-regulates in colorectal cancer tissues. High expression of NF-E1b is associated with poor prognosis of colorectal cancer patients. NF-E1b may serve as a potential target of the treatment for colorectal cancer. PMID- 27353106 TI - [Expression of CD133 in rectal cancer tissues and its relationship with neoadjuvant chemoradiotherapy]. AB - OBJECTIVE: To investigate the association of CD133 expression in rectal cancer tissues with neoadjuvant chemoradiotherapy (nCRT) and tumor regression grading (TRG) after nCRT. METHODS: Radical resected rectal cancer specimens and clinicopathological data of 105 patients, including 60 men and 45 women with median age of 59 years, diagnosed as locally advanced rectal cancer in Peking Union Medical College Hospital from January 2008 to December 2014 were collected retrospectively. Thirty-nine and 66 cases were histologically classified as good moderate and poor differentiation respectively. Sixty-eight and 37 cases were clinically graded as stage I(-II( and III(-IIII( in preoperative assessment respectively. NCRT was administered in 61 cases before surgery (nCRT group). The nCRT consisted of preoperative pelvic radiotherapy using 50 Gy (2 Gy once, for 25 sessions) with FOLFOX regimen (5-fluorouracil plus oxaliplatin) for 2-3 cycles or XELOX regimen (capecitabine plus oxaliplatin) for 2 cycles. Patients underwent surgery after 6 courses of nCRT, and then received the same previous chemotherapy regimen. In nCRT group, biopsy specimens before nCRT were obtained in 45 cases. Forty-four cases received surgery alone without nCRT (surgery alone group). CD133 expression was tested by immunohistochemical Envision two-step methods. The histological TRG evaluation was performed in the nCRT group. TRG score 0-2 was defined as insensitivity to nCRT, whereas TRG score 3-4 was defined as sensitivity. CD133 expression in rectal cancer samples before and after nCRT was compared. Association of CD133 expression with TRG after nCRT was examined. RESULTS: No significant differences of baseline parameters were found between nCRT group and surgery alone group (all P>0.05). The positive rate of CD133 in nCRT group was 70.4%(43/61,) which was significantly higher than that in surgery alone group (47.7%, 21/44)(chi(2)=5.566, P=0.018) and that in biopsy samples before nCRT group (44.4%, 20/45)(chi(2)=7.287, P=0.007). Twenty-two cases (36.1%, 22/61) in nCRT group had TRG score of 3-4 . Among these 22 cases, 11 cases were negative CD133, and constituted 61.1% (11/18) of all CD133-low expression cases in nCRT group, whereas the other 11 cases were positive CD133, and constituted 25.6%(11/43) of all CD133-high expression cases in nCRT group (chi(2)=6.974, P=0.008). CONCLUSION: The CD133 expression up-regulates markedly in rectal cancer after nCRT and nCRT may have potential positive modulation on CD133 expression. CD133-positive cancer reveals lower response to nCRT, suggesting CD133 may be a potential target for improving efficacy of nCRT in rectal cancer. PMID- 27353108 TI - [Efficacy meta-analysis of laparoscope-assisted transanal total mesorectal excision and conventional laparoscopic excision for rectal cancer]. AB - OBJECTIVE: To compare the short-term efficacy of laparoscope-assisted transanal total mesorectal excision (LA-taTME) and conventional laparoscopic TME (LTME) for rectal cancer by meta-analysis. METHODS: Clinical studies that compared clinical outcomes of LA-taTME and LTME were searched from form PubMed, Embase, Ovid, CNKI and Wanfang database before January 2016. Two reviewers independently screened the articles and assessed the quality of the included studies by using the MINORS standard which involves 12 items. The score is 0-2 for each item and the maximum score is 24, and the ideal global score should be above16. RevMan 5.3 software was used for meta-analysis and outcome measures included operation time, hospital stay, number of harvested lymph node, rate of conversion, positive rate of circumferential resection margin and the rate of incomplete mesorectum. RESULTS: Seven studies were included in the analysis, and the score of all the studies was more than 16 points. A total of 479 patients (208 in LA-taTME, 271 in LTME) were enrolled. There were no significant differences in terms of age, sex, tumor location and clinical stage between two groups (all P>0.05). Results of meta analysis showed that LA-taTME had lower rate of incomplete mesorectum (OR=0.29, 95% CI:0.10 to 0.84, P=0.02), lower rate of complications (OR=0.59, 95% CI:0.35 to 0.97, P=0.04) and shorter hospital stay (MD=-1.66, 95% CI:-3.22 to -0.11, P=0.04) than those of LTME, with significant differences. In terms of operation time (MD=-14.49, 95% CI:-37.87 to 8.90, P=0.22), number of harvested lymph node (MD=-0.45, 95% CI:-1.98 to 1.08, P=0.56), the rate of conversion (OR=0.31, 95% CI:0.08 to 1.24, P=0.10) and positive rate of circumferential resection margin (OR=0.43, 95% CI:0.17 to 1.04, P=0.06), there were no significant differences between two groups. CONCLUSION: Compared to LTME, LA-taTME has similar short-term efficacy for rectal cancer, but it can reduce the rate of complications and rate of incomplete mesorectum. PMID- 27353107 TI - [Effect of interleukin 17 on invasion of human colon cancer cells]. AB - OBJECTIVE: To investigate the effect and its possible mechanism of interleukin-17 (IL-17) on invasion and metastasis of human colon cancer cells. METHODS: IL-17 was added into the culture media of human colon cancer cells SW480 and LOVO. Cells were divided into 4 groups: SW480 control group (SW480 cells), LOVO control group (LOVO cells), SW480 experiment group (50 MUg/L IL-17+SW480 cells), and LOVO experiment group (50 MUg/L IL-17+LOVO cells). Cell growth was measured by CCK-8 assay. The proliferation rate(%)=[(Aexperiment group-Ablank)/(Acontrol group Ablank)]*100%). The ability of cell invasion and migration was measured by transwell assay. Real time-PCR was used to detect mRNA expression of VEGF and MMP 9. Western blot was performed to detect protein expression of STAT3, p-STAT3, VEGF and MMP-9. Enzyme-linked immunosorbent assay (ELISA) was applied to measure the protein content of VEGF and MMP-9 in the supernatant. RESULTS: After cultivation for 24, 48 and 72 hours, CCK-8 assay revealed that the proliferation rate of SW480 was 1.18%+/-0.07%, 1.42%+/-0.09%, and 1.62%+/-0.08%; the proliferation rate of LOVO was 1.13%+/-0.02%, 1.32%+/-0.05% and 1.73%+/-0.02% in experiment group. Transwell experiments showed that after cultivation with IL-17 for 24 hours, number of invasion cell in experimental groups (SW480: 34.00+/ 0.45, LOVO: 41.60+/-0.51) was higher as compared to corresponding control groups (SW480: 4.53+/-0.14; LOVO: 3.67+/-0.33) with significant differences (SW480: t= 76.026, P=0.001; LOVO: t=-81.580, P=0.005). The number of migration cell in experimental groups (SW480: 36.40+/-0.51, LOVO: 46.40+/-0.68) was higher as compared to corresponding control groups (SW480: 7.83+/-0.69; LOVO: 6.67+/-0.48) with significant differences (SW480: t=-51.542, P=0.003; LOVO: t=-49.265, P=0.005). Real-time PCR results revealed that after cultivation with IL-17 for 24 hours, VEGF and MMP-9 mRNA relative expression levels in experimental groups (SW480: VEGF:1.53+/-0.12, MMP-9: 2.44+/-0.23; LOVO: VEGF: 2.96+/-0.35, MMP-9: 3.38+/-0.55) were higher than those in control groups (both 1) with significant differences (VEGF: t=3.799, P=0.043; MMP-9: t=5.254, P=0.039). Western blot illustrated that after cultivation with IL-17 for 24 hours, STAT3, p-STAT3, VEGF and MMP-9 proteins relative expression levels in experimental groups were significantly higher that those in control groups (SW480:STAT3: t=3.233, P=0.023; p-STAT3: t=3.954, P=0.032; VEGF: t=3.201, P=0.025; MMP-9: t=3.154, P=0.029; LOVO: STAT3: t=3.788, P=0.012; p-STAT3: t=2.662, P=0.040; VEGF: t=4.118, P=0.035; MMP 9: t=4.268, P=0.030). ELISA indicated that content of VEGF and MMP-9 in the supernatant of experimental groups (SW480: VEGF 5 491.41+/-63.22, MMP-9: 21.43+/ 1.35. LOVO: VEGF: 8 631.46+/-129.59, MMP-9: 178.32+/-3.20) were higher than those in control groups (SW480: VEGF:4 456.32+/-87.56, MMP-9:18.57+/-2.44. LOVO: VEGF: 8 122.38+/-108.66, MMP-9: 163.22+/-6.89) with significant differences (SW480: VEGF: t=6.993, P=0.037; MMP-9: t=5.587, P=0.040. LOVO: VEGF: t=7.013, P=0.044; MMP-9: t=6.762, P=0.043). CONCLUSION: IL-17 may be able to activate STAT3 signal transduction pathway in vitro through up-regulation of VEGF and MMP-9 expression, thereby enhancing the invasion and migration of colon cancer SW480 and LOVO cells. PMID- 27353109 TI - [Role of transanal drainage tube in the prevention of anastomotic leakage after anterior resection for rectal cancer]. AB - Anastomotic leakage (AL) is one of the most serious complications of anterior resection for rectal cancer with morbidity about 10%. Distance of anastomosis to anal margin, underlying disease, surgical technique and perioperative situations are associated with AL. The transanal drainage tube (TDT) after anastomosis is gradually proved to be useful in prevention of AL. Most of the literatures suggest that TDT is simple and safe, and can reduce the incidence of AL. The materials and the operating process of TDT have been universalized gradually: application of silicone or rubber material, large lumen with several side holes, placement at a distance of 3 to 5 cm above the anastomosis for 5 to 7 days. However, selection bias existed in previous studies, and the main problems were disunity of enrolling standard and exclusion of patients with high AL risk, which would not fully reflect the value of TDT. Defunctioning stoma (or diverting stoma, DS) is a common method to prevent and treat the AL. At present, efficacy comparison between TDT and DS remains controversial. Thus, randomized, double blind, controlled trials are needed to investigate the value of TDT in prevention of AL after anterior resection, especially for middle and low rectal cancer. PMID- 27353110 TI - [Application and prospect of circulating tumor cells detection in colorectal cancer]. AB - About 30%-50% of colorectal cancer patients would develop recurrence and metastasis. At present, there is still a lack of effective evaluation method for recurrence, metastasis and prognosis. In recent years, a great progress about circulating tumor cells (CTC) in diagnosis and treatment of colorectal cancer has been made. The most common CTC detection methods include immunocytochemistry, flow cytometry, PCR, immunomagnetic separation, optical fiber array scanning and CTC chip. Based on present studies, researchers reach the consensus that CTC is clinically valuable in the following aspects: detection of occult metastasis, monitor of disease progress and evaluation of response to treatment. With recent development of clinical specialization, multi-disciplinary treatment (MDT), gene detection and targeted therapy, individualized treatment may greatly improve overall survive and disease-free survival of colorectal cancer patients. However, the methods above depend on tumor tissues that are always impractical to obtain for late stage and non-surgery patients. Moreover, the size of specimen is always small, making gene expression and mutation detection difficult. CTC detection may solve such problems based on molecular biology with high plausibility and repeatability. Therefore, CTC detection can be used as a new diagnosis tool. It is believed that CTC detection will play an important role in early diagnosis, evaluating recurrence, metastasis, making individualized treatment and predicting prognosis. PMID- 27353111 TI - Dysregulation of hypothalamic modulation in olanzapine treated male rats. PMID- 27353112 TI - Acute stress induces increases in salivary IL-10 levels. AB - The purpose of this study was to investigate the stress-reactivity of the anti inflammatory cytokine, IL-10, in saliva and to determine how salivary IL-10 levels change in relation to those of IL-1beta, a pro-inflammatory cytokine, following stress. Healthy young adults were randomly assigned to retrieve a negative emotional memory (n = 46) or complete a modified version of the Trier Social Stress Test (n = 45). Saliva samples were taken 10 min before (baseline) and 50 min after (post-stressor) onset of a 10-min stressor, and were assayed using a high sensitivity multiplex assay for cytokines. Measurable IL-10 levels (above the minimum detectable concentration) were found in 96% of the baseline samples, and 98% of the post-stressor samples. Flow rate-adjusted salivary IL-10 levels as well as IL-1beta/IL-10 ratios showed moderate but statistically significant increases in response to stress. Measurement of salivary IL-10 and pro-/anti-inflammatory cytokine ratios may be useful, noninvasive tools, in stress research. PMID- 27353113 TI - Effect of glucose on Listeria monocytogenes biofilm formation, and assessment of the biofilm's sanitation tolerance. AB - Listeria monocytogenes is an important cause of human foodborne infections and its ability to form biofilms is a serious concern to the food industry. To reveal the effect of glucose conditions on biofilm formation of L. monocytogenes, 20 strains were investigated under three glucose conditions (0.1, 1.0, and 2.0% w v( 1)) by quantifying the number of cells in the biofilm and observing the biofilm structure after incubation for 24, 72, and 168 h. In addition, the biofilms were examined for their sensitivity to sodium hypochlorite. It was found that high concentrations of glucose reduced the number of viable cells in the biofilms and increased extracellular polymeric substance production. Moreover, biofilms formed at a glucose concentration of 1.0 or 2.0% were more resistant to sodium hypochlorite than those formed at a glucose concentration of 0.1%. This knowledge can be used to help design the most appropriate sanitation strategy. PMID- 27353114 TI - Detection, differentiation, and identification of botulinum neurotoxin serotypes C, CD, D, and DC by highly specific immunoassays and mass spectrometry. AB - Botulinum neurotoxin (BoNT) serotypes C and D and their mosaic variants CD and DC cause severe cases of botulism in animal husbandry and wildlife. Epidemiological data on the exact serotype or toxin variant causing outbreaks are rarely available, mainly because of their high sequence identity and the lack of fast and specific screening tools to detect and differentiate the four similar toxins. To fill this gap, we developed four highly specific sandwich enzyme-linked immunosorbent assays (ELISAs) able to detect and differentiate botulinum neurotoxins type BoNT/C, D, CD, and DC based on four distinct combinations of specific monoclonal antibodies targeting both conserved and divergent subdomains of the four toxins. Here, highly sensitive detection with detection limits between 2 and 24 pg mL(-1) was achieved. The ELISAs were extensively validated and results were compared with data obtained by quantitative real-time PCR using a panel of Clostridium botulinum strains, real sample materials from veterinary botulism outbreaks, and non-BoNT-producing Clostridia. Additionally, in order to verify the results obtained by ELISA screening, the new monoclonal antibodies were used for BoNT enrichment and subsequent detection (i) on a functional level by endopeptidase mass spectrometry (Endopep-MS) assays and (ii) on a protein sequence level by LC-MS/MS spectrometry. Based on all technical information gathered in the validation study, the four differentiating ELISAs turned out to be highly reliable screening tools for the rapid analysis of veterinary botulism cases and should aid future field investigations of botulism outbreaks and the acquisition of epidemiological data. PMID- 27353115 TI - The persistence length of adsorbed dendronized polymers. AB - The persistence length of cationic dendronized polymers adsorbed onto oppositely charged substrates was studied by atomic force microscopy (AFM) and quantitative image analysis. One can find that a decrease in the ionic strength leads to an increase of the persistence length, but the nature of the substrate and of the generation of the side dendrons influence the persistence length substantially. The strongest effects as the ionic strength is being changed are observed for the fourth generation polymer adsorbed on mica, which is a hydrophilic and highly charged substrate. However, the observed dependence on the ionic strength is much weaker than the one predicted by the Odijk, Skolnik, and Fixman (OSF) theory for semi-flexible chains. Low-generation polymers show a variation with the ionic strength that resembles the one observed for simple and flexible polyelectrolytes in solution. For high-generation polymers, this dependence is weaker. Similar dependencies are found for silica and gold substrates. The observed behavior is probably caused by different extents of screening of the charged groups, which is modified by the polymer generation, and to a lesser extent, the nature of the substrate. For highly ordered pyrolytic graphite (HOPG), which is a hydrophobic and weakly charged substrate, the electrostatic contribution to the persistence length is much smaller. In the latter case, we suspect that specific interactions between the polymer and the substrate also play an important role. PMID- 27353116 TI - Defining Taiwanese children's health literacy abilities from a health promotion perspective. AB - BACKGROUND: Health literacy is related to health inequality, health behaviors, and health status. Globally, health literacy has primarily focused on adults and has been based on the medical model. It is necessary to understand children's life experiences as they relate to health; thus, this study attempted to evaluate and describe the health literacy abilities of sixth-graders in Taiwan. METHODS: Interviews were conducted with 10 teachers and 11 caregivers, and focus groups were conducted with 32 children. Health literacy abilities corresponding to real life situations were identified from life skills and the Taiwanese Curriculum Guidelines for health education. Three expert meetings were held to redefine children's health literacy using a health promotion perspective and confirmed indicators. RESULTS: An operational definition of three aspects of children's health literacy and 25 abilities was proposed: 11 functional health literacy abilities (e.g. understands the connection between personal health care behaviors and health); seven interactive health literacy abilities (e.g. obtains and understands information from various channels); and seven critical health literacy abilities (e.g. analyzes the relationship between personal needs and diet choices for a balanced diet). These indicators cover 10 health education categories. CONCLUSIONS: These findings highlight the importance of understanding Taiwanese children's health literacy, and the urgency of developing an appropriate measurement tool. The definition and indicators in this study were identified using a child-centered approach focusing on children's real-life experiences. The result serves as a solid basis for the development of the Taiwan Children's Health Literacy Scale, and provides information for the decision making sector on health education. PMID- 27353117 TI - A qualitative study of tobacco use in eight economically disadvantaged Dominican Republic communities. AB - Understanding social conditions prior to intervention design can enhance tobacco control interventions. This paper describes formative research conducted in 2010 about tobacco use in eight economically disadvantaged Dominican Republic communities, four of which participated in a previous intervention study (2003 2008). A combined US-Dominican team used a rapid assessment process to collect qualitative social and cultural data on tobacco use, knowledge and attitudes; plus observations about social and policy factors, such as exposure to secondhand smoke (SHS), tobacco regulations, pregnancy, health care provider (HCP) practices and sustainability of the 2003-2008 intervention. This assessment found that tobacco use varied by age. While all ages typically used cigarettes, older adults used relatively more unprocessed tobacco, which is seen as less harmful and less addictive. Middle-aged smokers typically used commercial cigarettes, which are viewed as dangerous, addictive, expensive and offensive. Young adults reported avoiding smoking, but using relatively more smokeless tobacco. Smoking during pregnancy has reportedly decreased. SHS was viewed as harmful, although smoke free homes were uncommon. HCPs discussed tobacco issues mostly for patients with tobacco-related conditions. Sustainability of the 2003-2008 intervention appeared to be linked to active Community Technology Centers with strong leadership, and community social capital. This information could be used to design better targeted interventions in these communities. PMID- 27353118 TI - The relationship between insufficient milk perception and breastfeeding self efficacy among Turkish mothers. AB - OBJECTIVE: This study was conducted to investigate the relationship between perceived insufficient milk and breastfeeding self-efficacy levels among Turkish mothers. METHODS: The study was conducted on 200 mothers whose infants were hospitalized and under treatment and who could breastfeed their infants in the newborn clinic of a university hospital in eastern Turkey between June 2013 and February 2014. A sampling method was not applied in the study, so the sample consisted of the population of the study. The 'Personal Information Form', 'Breastfeeding Self-Efficacy Scale' and 'Perception of Insufficient Milk Questionnaire' were used to collect the data. Data were analysed by using percentage distribution and arithmetic average; independent sample t test, Mann Whitney U test, Kruskal-Wallis variance analysis, Pearson correlation analysis and Cronbach alpha reliability coefficiency in the SPSS 18.0 package program. RESULTS: The study determined that advanced age, higher education level and higher income status, male gender of the child, planning of the pregnancy, many births, receiving breastfeeding education and the length of time that mothers planned to exclusively breastfeed affected breastfeeding self-efficacy and perception of milk sufficiency positively ( p<0.05). The study showed that, as breastfeeding self-efficacy levels of mothers increased, their perception of milk sufficiency also increased ( p<0.05). CONCLUSION: The study concluded that some factors related to the mother, infant, pregnancy and breastfeeding affected breastfeeding self-efficacy and the perception of milk insufficiency. As the breastfeeding self-efficacy level increased, the milk was perceived to be more sufficient. PMID- 27353119 TI - Correlates of psychological outcomes in people with diabetes: results from the second Diabetes Attitudes, Wishes and Needs (DAWN2(TM) ) study. AB - AIMS: To assess country- and individual-level correlates of psychological outcomes, and differences among countries in the associations of individual characteristics with psychological outcomes among adults with diabetes. METHODS: The second Diabetes Attitudes, Wishes and Needs (DAWN2(TM) ) study assessed self reported characteristics of people with diabetes in 17 countries, including 1368 adults with Type 1 diabetes and 7228 with Type 2 diabetes. In each country, a sample of 500 adults, stratified by diabetes type and treatment, completed a questionnaire incorporating the validated WHO-5 wellbeing index, the WHOQOL-BREF, and the five-item Problem Areas in Diabetes Scale, as well as the newly developed Diabetes Impact on Life Dimensions that assessed impact ranging from very positive to very negative, with no impact as the midpoint. Multilevel regression analyses identified significant (P < 0.05) independent correlates of psychological outcomes. RESULTS: There were significant variations in all outcomes across countries before adjustment for individual-level factors; adjustment reduced between-country disparities. Worse psychological outcomes were associated with more complications, incidence of hypoglycaemia, hypoglycaemic medication, perceived burden of diabetes, family conflict and experience of discrimination. Better psychological outcomes were associated with higher self rated health, greater access to diabetes education and healthcare, and more psychosocial support from others. The associations of many factors with the outcomes were mediated by modifiable factors. The association of all factors with the outcomes varied across (interacted with) countries, highlighting the need for country-specific analyses. CONCLUSIONS: Improvements in modifiable risk factors (reductions in burden and increases in support) may lead to better psychological outcomes in adults with diabetes. PMID- 27353120 TI - Editorial Comment to Association between body mass index and outcomes in Japanese living kidney transplant recipients: The role of sex differences. PMID- 27353121 TI - Prenatal diagnosis for haemophilia: the Thai experience. AB - BACKGROUND: Haemophilia is a lifelong X-linked recessive inherited bleeding disorder. Since the haemophilia management in economically less-developed countries is inadequately provided, prevention of new cases of haemophilia is essentially required. SUBJECTS AND METHODS: A total of 42 pregnancies in 37 women at risk for severe and moderate haemophilia (A = 33, B = 4) were enrolled. The prenatal diagnostic (PND) procedure was performed in 32 women, while 10 women refused further PND procedure after knowing their foetuses were female (n = 8) and male (n = 2). The foetal specimen was obtained through chorionic villus sampling (n = 14), amniocentesis (n = 1) and cordocentesis (n = 17). The status of haemophilia was determined using informative RFLP markers and inversion of intron 22 of the F8 gene, and/or foetal FVIII:C or FIX:C. RESULTS: The final diagnosis revealed normal males (n = 18), haemophilia A males (n = 9), normal females (n = 3) and haemophilia A carrier females (n = 2). All women with affected haemophilia sons requested to terminate their pregnancies except one woman. One of 32 pregnancies (3.1%) had spontaneous abortion. At follow-up after birth, the PND was accurately confirmed in one haemophilia A male, three normal females and two carrier females by laboratory testing, and 18 unaffected normal males by history taking of no bleeding manifestations. However, 10 women who continued their pregnancies after knowing foetal sex turned out to have two haemophilia A males, one normal female, one haemophilia A carrier female and six normal or carrier females. CONCLUSION: The PND of haemophilia could be accurately determined but it was not well accepted by all couples at risk. PMID- 27353122 TI - Fusion and fission of molecular assemblies of amphiphilic polypeptides generating small vesicles from nanotubes. AB - Three amphiphilic block polypeptides, (sarcosine)m -b-(l- or d-Leu-Aib)n (L16, D16, D14), having different helical chain lengths or helicity are synthesized. A mixture of L16, D16, and D14 generates vesicles of diameters more than ca. 130 nm by injecting the ethanol solution into water and heating at 90 degrees C for 1 h. On the other hand, when nanotubes composed of L16 and D14 having ca. 50 nm diameter are mixed with nanosheets composed of D16, smaller and homogeneous vesicles of ca. 60 nm diameter are obtained with the heat treatment. The time lapse TEM image analysis of the mixtures revealed some transient structures of nanotubes sticking a nanosheet or a vesicle at the open end of nanotubes. The precise size control of vesicles is therefore attainable by using nanotubes as a structural template regulating the size of vesicles near to the nanotube diameter upon the membrane fission processes. PMID- 27353123 TI - Selenium-Containing Fused Bicyclic Heterocycle Diselenolodiselenole: Field Effect Transistor Study and Structure-Property Relationship. AB - The first application of the diselenolodiselenole (C4Se4) heterocycle as an active organic field effect transistor materials is demonstrated here. C4Se4 derivatives (2a-2d) were obtained by using a newly developed straightforward diselenocyclization protocol, which includes the reaction of diynes with selenium powder at elevated temperature. C4Se4 derivatives exhibit strong donor characteristics and planar structure (except 2d). The atomic force microscopic analysis and thin-film X-ray diffraction pattern of compounds 2a-2d indicated the formation of distinct crystalline films that contain large domains. A scanning electron microscopy study of compound 2b showed development of symmetrical grains with an average diameter of 150 nm. Interestingly, 2b exhibited superior hole mobility, approaching 0.027 cm(2) V(-1) s(-1) with a transconductance of 9.2 MUS. This study correlate the effect of pi-stacking, Se...Se intermolecular interaction, and planarity with the charge transport properties and performance in the field effect transistor devices. We have shown that the planarity in C4Se4 derivatives was achieved by varying the end groups attached to the C4Se4 core. In turn, optoelectronic properties can also be tuned for all these derivatives by end-group variation. PMID- 27353124 TI - Association of cognitive function with tooth loss and mitochondrial variation in adult subjects: a community-based study in Beijing, China. AB - OBJECTIVES: Cognitive impairment is a common neurological problem in elderly people. In this study, we investigated whether tooth loss, periodontal parameters, and gene variations in the mitochondrial DNA displacement loop region are potential influencing factors on cognitive function. DESIGN: We employed a linear regression model to estimate cross-sectional association between number of teeth lost, periodontal parameters and Mini-mental State Examination score, adjusting for demographic factors, socioeconomic factors, general health status, smoking, drinking, and life habits. PARTICIPANTS: A total of 905 Han Chinese people, >=50 years of age, with complete data, were enrolled. Blood samples of 567 of the subjects were analyzed for correlation between mitochondrial DNA variants and Mini-mental State Examination score. RESULTS: The number of teeth lost (beta = -0.042, 95% CI: -0.061, -0.024, P < 0.001), two single nucleotide polymorphism (SNP) points: A189G (beta = -1.540, 95% CI: -2.818, -0.263, P = 0.018) and A16164G (beta = -1.053, 95% CI: -2.054, -0.052, P = 0.039) in the mitochondrial DNA displacement loop region, and haplogroup Y (beta = -2.152, 95% CI: -4.062, -0.242, P = 0.027) were found to be negatively associated with Mini mental State Examination scores in the fully adjusted model. No correlation was found between periodontal parameters and Mini-mental State Examination scores. CONCLUSION: Number of teeth lost, mitochondrial SNPs, and haplogroup Y were correlated with cognitive function in this study population. PMID- 27353125 TI - Prospective Memory in Posttraumatic Stress Disorder. AB - OBJECTIVES: Neuropsychological studies of posttraumatic stress disorder (PTSD) have revealed deficits in attention/working memory, processing speed, executive functioning, and retrospective memory. However, little is known about prospective memory (PM) in PTSD, a clinically relevant aspect of episodic memory that supports the encoding and retrieval of intentions for future actions. METHODS: Here we examined PM performance in 40 veterans with PTSD compared to 38 trauma comparison (TC) veterans who were exposed to combat but did not develop PTSD. All participants were administered the Memory for Intentions Test (MIST; Raskin, Buckheit, & Sherrod, 2010), a standardized and validated measure of PM, alongside a comprehensive neurocognitive battery, structured diagnostic interviews for psychiatric conditions, and behavioral questionnaires. RESULTS: Veterans with PTSD performed moderately lower than TC on time-based PM, with errors primarily characterized as PM failure errors (i.e., omissions). However, groups did not differ in event-based PM, ongoing task performance, or post-test recognition of PM intentions for each trial. Lower time-based PM performance was specifically related to hyperarousal symptoms of PTSD. Time-based-performance was also associated with neuropsychological measures of retrospective memory and executive functions in the PTSD group. Nevertheless, PTSD was significantly associated with poorer PM above and beyond age and performance in retrospective memory and executive functions. DISCUSSION: Results provide initial evidence of PM dysfunction in PTSD, especially in strategic monitoring during time-based PM tasks. Findings have potential implications for everyday functioning and health behaviors in persons with PTSD, and deserve replication and future study. (JINS, 2016, 22, 724-734). PMID- 27353127 TI - Exercise capacity in left ventricular assist device patients with full and partial support. AB - Background In the present work, we investigated the exercise capacities of patients with partial flow left ventricular assist devices and its evolution over time. We then compared the exercise capacities of these patients with those of full support ventricular assist device patients. Methods We retrospectively analysed the data of maximal cardiopulmonary exercise tests of ten partial support patients (CircuLite Synergy(r) Micropump) collected before (PS0), at 3 (PS3) and 6 months (PS6) after implantation. The data were then compared with those of 17 patients (FS6) treated with a full support device (HeartMate II, Thoratec(c)). For this analysis, we considered the exercise tests performed at 6 months after pump implantation for both groups. Results Peak oxygen uptake evolved in the PS0, PS3 and PS6 groups from 11.5 +/- 2.3 to 12.6 +/- 2.8 and 12.0 +/- 2.7 mL/kg/min, respectively. Heart rate peak increased from PS0 to PS6 (100 +/- 17 bpm and 107 +/- 22 bpm, p = 0.05). The comparative analysis between PS6 and FS6 groups showed no difference in terms of exercise performance (12.0 +/- 2.7 and 13.5 +/- 3.0 mL/kg/min, respectively), fatigue perception, ventilation efficiency slope, anaerobic threshold and oxygen uptake efficiency slope. The chronotropic response was also similar in both PS6 and FS6 groups. However, PS6 patients were more often treated with beta-blockers and therefore had lower heart rates at rest and at peak exercise than FS6 patients. Conclusions Exercise performance does not change after partial support implantation and stays stable over time. Partial and full support patients show similar exercise performances that attain 41% and 46% of the expected values, respectively. PMID- 27353126 TI - 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts): Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). PMID- 27353128 TI - A review of guidelines for cardiac rehabilitation exercise programmes: Is there an international consensus? AB - BACKGROUND: Cardiac rehabilitation is an important component in the continuum of care for individuals with cardiovascular disease, providing a multidisciplinary education and exercise programme to improve morbidity and mortality risk. Internationally, cardiac rehabilitation programmes are implemented through various models. This review compared cardiac rehabilitation guidelines in order to identify any differences and/or consensus in exercise testing, prescription and monitoring. METHODS: Guidelines, position statements and policy documents for cardiac rehabilitation, available internationally in the English language, were identified through a search of electronic databases and government and cardiology society websites. Information about programme delivery, exercise testing, prescription and monitoring were extracted and compared. RESULTS: Leading cardiac rehabilitation societies in North America and Europe recommend that patients progress from moderate- to vigorous-intensity aerobic endurance exercise over the course of the programme, with resistance training included as an important adjunct, for maintaining independence and quality of life. North American and European guidelines also recommend electrocardiograph-monitored exercise stress tests. Guidelines for South America and individual European nations typically include similar recommendations; however, those in the United Kingdom, Australia and New Zealand specify lower-intensity exercise and less technical assessment of functional capacity. CONCLUSION: Higher-intensity aerobic training programmes, supplemented by resistance training, have been recommended and deemed safe for cardiac rehabilitation patients by many authorities. Based on research evidence, this may also provide superior outcomes for patients and should therefore be considered when developing an international consensus for exercise prescription in cardiac rehabilitation. PMID- 27353129 TI - Ethnic differences in case fatality following an acute ischaemic heart disease event in New Zealand: ANZACS-QI 13. AB - BACKGROUND: The aim of this study was to investigate ischaemic heart disease (IHD) case fatality in high-risk ethnic populations in New Zealand. DESIGN: This is a national data-linkage study using anonymised hospitalisation and mortality data. METHODS: Linked individual patient data were used to identify 35-84-year olds who experienced IHD events (acute IHD hospitalisations and/or deaths) in 2009-2010. Subjects were classified as: (i) hospitalised with IHD and alive at 28 days post-event; (ii) hospitalised with IHD and died within 28 days; (iii) hospitalised with a non-IHD diagnosis and died from IHD within 28 days; or (iv) died from IHD but not hospitalised. Multinomial logistic regression was used to estimate the proportion of people in each group, as well as overall 28-day case fatality, adjusted for ethnic differences in demographic and comorbidity profiles. RESULTS: A total of 26,885 people experienced IHD events (11.3% Maori, 4.0% Pacific and 2.5% Indian); 3.3% of people died within 28 days of IHD hospitalisations, 5.1% died of IHD within 28 days of non-IHD hospitalisations and 13.0% died of IHD without any recent hospitalisation. Overall adjusted case fatality was 12.6% in Indian, 20.5% in European, 26.0% in Pacific and 27.6% in Maori people. Compared to Europeans, the adjusted odds of death were approximately 50% higher in Maori and Pacific people and 50% lower in Indians, regardless of whether they were hospitalised. CONCLUSIONS: Major ethnic inequalities in IHD case fatality occur with and without associated hospitalisations. Improvements in both primary prevention and hospital care will be required to reduce inequalities. PMID- 27353130 TI - ST segment/heart rate hysteresis improves the diagnostic accuracy of ECG stress test for coronary artery disease in patients with left ventricular hypertrophy. AB - BACKGROUND: The exercise electrocardiographic stress test (ExET) is the most widely used non-invasive diagnostic method to detect coronary artery disease. However, the sole ST depression criteria (ST-max) have poor specificity for coronary artery disease in patients with left ventricular hypertrophy. We hypothesised that ST-segment depression/heart rate hysteresis, depicting the relative behaviour of ST segment depression during the exercise and recovery phase of the test might increase the diagnostic accuracy of ExET for coronary artery disease detection in such patients. METHODS: In three cardiology centres, we studied 113 consecutive patients (mean age 66 +/- 2 years; 88% men) with hypertension-related left ventricular hypertrophy at echocardiography, referred to coronary angiography after an ExET. The following ExET criteria were analysed: ST-max, chronotropic index, heart rate recovery, Duke treadmill score, ST-segment depression/heart rate hysteresis. RESULTS: We detected significant coronary artery disease at coronary angiography in 61 patients (53%). At receiver operating characteristic analysis, ST-segment depression/heart rate hysteresis had the highest area under the curve value (0.75, P < 0.001 when compared with the 'neutral' receiver-operating characteristic curve value of 0.5). Area under the curve values were 0.68 (P < 0.01) for the chronotropic index, 0.58 (P = NS) for heart rate recovery, 0.57 (P = NS) for ST-max and 0.52 (P = NS) for the Duke treadmill score. CONCLUSIONS: Among currently available ExET diagnostic variables, ST-segment depression/heart rate hysteresis offers a substantially better diagnostic accuracy for coronary artery disease than conventional criteria in patients with hypertension-related left ventricular hypertrophy. PMID- 27353131 TI - Understanding malarial toxins. AB - Recognized since antiquity, malaria is one of the most infamous and widespread infectious diseases in humans and, although the death rate during the last century has been diminishing, it still accounts for more than a half million deaths annually. It is caused by the Plasmodium parasite and typical symptoms include fever, shivering, headache, diaphoresis and nausea, all resulting from an excessive inflammatory response induced by malarial toxins released into the victim's bloodstream. These toxins are hemozoin and glycosylphosphatidylinositols. The former is the final product of the parasite's detoxification of haeme, a by-product of haemoglobin catabolism, while the latter anchor proteins to the Plasmodium cell surface or occur as free molecules. Currently, only two groups of antimalarial toxin drugs exist on the market, quinolines and artemisinins. As we describe, they both target biosynthesis of hemozoin. Other substances, currently in various phases of clinical trials, are directed towards biosynthesis of glycosylphosphatidylinositol, formation of hemozoin, or attenuation of the inflammatory response of the patient. Among the innovative approaches to alleviating the effects of malarial toxins, is the development of antimalarial toxin vaccines. In this review the most important lessons learned from the use of treatments directed against the action of malarial toxins in antimalarial therapy are emphasized and the most relevant and promising directions for future research in obtaining novel antimalarial agents acting on malarial toxins are discussed. PMID- 27353132 TI - Gastrointestinal dysfunction and enteric neurotoxicity following treatment with anticancer chemotherapeutic agent 5-fluorouracil. AB - BACKGROUND: The use of the anticancer chemotherapeutic agent 5-fluorouracil (5 FU) is often limited by nausea, vomiting, constipation, and diarrhea; these side effects persist long after treatment. The effects of 5-FU on enteric neurons have not been studied and may provide insight into the mechanisms underlying 5-FU induced gastrointestinal dysfunction. METHODS: Balb/c mice received intraperitoneal injections of 5-FU (23 mg/kg) 3 times/week for 14 days. Gastrointestinal transit was analysed in vivo prior to and following 3, 7, and 14 days of 5-FU treatment via serial x-ray imaging. Following 14 days of 5-FU administration, colons were collected for assessment of ex vivo colonic motility, gross morphological structure, and immunohistochemical analysis of myenteric neurons. Fecal lipocalin-2 and CD45+ leukocytes in the colon were analysed as markers of intestinal inflammation. KEY RESULTS: Short-term administration of 5 FU (3 days) increased gastrointestinal transit, induced acute intestinal inflammation and reduced the proportion of neuronal nitric oxide synthase immunoreactive neurons. Long-term treatment (7, 14 days) resulted in delayed gastrointestinal transit, inhibition of colonic migrating motor complexes, increased short and fragmented contractions, myenteric neuronal loss and a reduction in the number of ChAT-immunoreactive neurons after the inflammation was resolved. Gross morphological damage to the colon was observed following both short- and long-term 5-FU treatment. CONCLUSIONS & INFERENCES: Our results indicate that 5-FU induces accelerated gastrointestinal transit associated with acute intestinal inflammation at day 3 after the start of treatment, which may have led to persistent changes in the ENS observed after days 7 and 14 of treatment contributing to delayed gastrointestinal transit and colonic dysmotility. PMID- 27353133 TI - Little effects of reduced-impact logging on insect communities in eastern Amazonia. AB - Selective logging has become a major source of threats to tropical forest, bringing challenges for both ecologists and managers to develop low-impact forestry. Reduced-impact logging (RIL) is a prominent activity accounting for such forestry practices to prevent strong forest disturbances. Our aims were to evaluate the effects of RIL on insect communities of forested streams from Eastern Amazon and to test the hypothesis of negative effects of RIL on species richness, abundance, and functional feeding groups of aquatic insect assemblages. Neither of the evaluated metrics of the studied assemblages were negatively affected by RIL. Environmental metrics, such as substrate heterogeneity, woody canopy cover, and hill slope height, varied more among RIL streams than in reference streams, indicating a gradient according to logging impacts, and are suitable candidates to monitor RIL impacts in Amazonian streams. In addition, the PHI index also varied among REF and RIL, according to age class and year of logging, which could reflect trends to recover the forest structure after logging in a time frame of only 10 years. We conclude that RIL impacts have not had detrimental impacts on insect communities, but have changed little of the environmental conditions, especially of the riparian vegetation around streams. PMID- 27353134 TI - Occurrence of selected estrogenic compounds and estrogenic activity in surface water and sediment of Langat River (Malaysia). AB - The occurrence and estrogenic activities of steroid estrogens, such as the natural estrone (E1), 17beta estradiol (E2), and estriol (E3), as well as the synthetic 17alpha-ethynylestradiol (EE2), were investigated in eight sampling points along the Langat River (Malaysia). Surface water samples were collected at 0.5 m and surface sediment 0-5 cm from the river surface. Instrument analysis of steroid estrogens was determined by UPLC-ESI-MS with an ultra-performance liquid chromatograph (Perkin Elmer FX15) coupled to a Q Trap function mass spectrophotometer (model 3200: AB Sciex). Steroid estrogen concentrations were higher in the Langat River sediments than those in its surface water. In surface water, E1 was not detected in any sampling point, E2 was only detected in two midstream sampling points (range 0-0.004 ng/L), E3 in three sampling points (range 0-0.002 ng/L), and EE2 in four sampling points (range 0-0.02 ng/L). E1 and E2 were detected in sediments from all sampling points, E3 in five sampling points, while EE2 only in one midstream sample (3.29E-4 ng/g). Sewage treatment plants, farming waste, and agricultural activities particularly present midstream and downstream were identified as potential sources of estrogens. Estrogenic activity expressed as estradiol equivalents (EEQs) was below 1 ng/L in all samples for both surface water and sediment, indicating therefore a low potential estrogenic risk to the aquatic environment. Although the health risks are still uncertain for drinking water consumers exposed to low levels of steroid estrogen concentrations, Langat River water is unacceptable for direct drinking purposes without treatment. Further studies of endocrine disruptors in Malaysian waters are highly recommended. PMID- 27353135 TI - Surface water pH variations and trends in China from 2004 to 2014. AB - With economic development and the increase of energy consumption, surface water acidification has been a potential environmental concern in China. Here, we analyzed variations and trends in surface water pH of 73 sites from ten river basins in China from 2004 to 2014 with nonparametric Seasonal Kendall test method. Our analysis showed that the variations of surface water pH in China ranged from 6.5 to 9.0 in the past decade (2004-2014), which satisfied the water quality criteria in pH for protection of aquatic ecosystems in China (6.0-9.0) and USA (6.5-9.0). However, significant decreasing trends in surface water pH were found in 31 monitoring sites, which were mainly located in Haihe River, Taihu Lake and Yangtze River, while the pH value showed significant increasing trends in 22 sites, which mainly were located in Songhua River and Pearl River. Our results suggested the increased potential acidification of susceptible water bodies in China. Besides the control policy of sulfur dioxide (SO2) emissions, the emissions of nitrous oxides (NOx) should also be reduced to protect the aquatic systems in China. PMID- 27353136 TI - Membrane protein assembly: two cytoplasmic phosphorylated serine sites of Vpu from HIV-1 affect oligomerization. AB - Viral protein U (Vpu) encoded by human immunodeficiency virus type 1 (HIV-1) is a short integral membrane protein which is known to self-assemble within the lipid membrane and associate with host factors during the HIV-1 infectivity cycle. In this study, full-length Vpu (M group) from clone NL4-3 was over-expressed in human cells and purified in an oligomeric state. Various single and double mutations were constructed on its phosphorylation sites to mimic different degrees of phosphorylation. Size exclusion chromatography of wild-type Vpu and mutants indicated that the smallest assembly unit of Vpu was a dimer and over time Vpu formed higher oligomers. The rate of oligomerization increased when (i) the degree of phosphorylation at serines 52 and 56 was decreased and (ii) when the ionic strength was increased indicating that the cytoplasmic domain of Vpu affects oligomerization. Coarse-grained molecular dynamic simulations with models of wild-type and mutant Vpu in a hydrated lipid bilayer supported the experimental data in demonstrating that, in addition to a previously known role in downregulation of host factors, the phosphorylation sites of Vpu also modulate oligomerization. PMID- 27353137 TI - Protein-Ligand Informatics Force Field (PLIff): Toward a Fully Knowledge Driven "Force Field" for Biomolecular Interactions. AB - The Protein Data Bank (PDB) contains a wealth of data on nonbonded biomolecular interactions. If this information could be distilled down to nonbonded interaction potentials, these would have some key advantages over standard force fields. However, there are some important outstanding issues to address in order to do this successfully. This paper introduces the protein-ligand informatics "force field", PLIff, which begins to address these key challenges ( https://bitbucket.org/AstexUK/pli ). As a result of their knowledge-based nature, the next-generation nonbonded potentials that make up PLIff automatically capture a wide range of interaction types, including special interactions that are often poorly described by standard force fields. We illustrate how PLIff may be used in structure-based design applications, including interaction fields, fragment mapping, and protein-ligand docking. PLIff performs at least as well as state-of the art scoring functions in terms of pose predictions and ranking compounds in a virtual screening context. PMID- 27353138 TI - [Detection of alpha-1 antitrypsin deficiency: A study on patients diagnosed with chronic obstructive pulmonary disease in primary health care]. AB - The prevalence of chronic obstructive pulmonary disease (COPD) in Spain is 10.2%. Although tobacco is the main aetiological factor, biomass smoke exposure and alpha-1 antitrypsin deficiency (AATD) have also been related to its development. AATD is a genetic condition which could be causing 2-3% of COPD cases. The aim of this cross-sectional descriptive study was to exclude the existence of AATD in a population of COPD patients from CS Culleredo, A Coruna. The thick blood drop test on blotting paper, as well as the analysis of the mutations PI*S and PI*Z of the gene SERPINA 1 by the analysis of denaturing gradients after simultaneous amplification related to PCR (polymerase chain reaction). The study population included 80 patients between 40-80 years old, of whom 30% were carriers of a deficient allele (heterozygous), and 80% of them were the allele PiS. Only one PiSZ (1.25%) individual and no PiZZ was detected. This represents an allelic frequency of 3.1% (PiZ), and 13.1% (PiS). The detected allelic frequencies are higher than previously reported in the Spanish population. Severe AATD has been excluded in 98.75% of the study population. The Pi*SZ patient has been diagnosed in an early stage of the disease. We have also achieved one of the quality indicators recommended by GesEPOC. Our area has shown a high PiS and PiZ frequency, thus our study could be used as a reference for further research in the Galician population. PMID- 27353139 TI - [Professional development and maintenance]. PMID- 27353140 TI - [Chest impalement: Presentation of a case]. PMID- 27353141 TI - [Perceived quality of life in the "healthy people" municipal community health promotion program in Ciudad Lineal-Madrid]. AB - INTRODUCTION: The measurement of the health-related quality of life (HRQoL) is a comprehensive way to estimate the health of both the individual and the community. The aim of this study was to assess changes in health and HRQoL using the intervention strategies "healthy people" and "health promotion programs" of the City Council of Madrid-Madrid Health. The study was conducted in the Municipal Health Centre of Ciudad Lineal, in 2014, and included promotion of exercise, healthy eating, smoking cessation, psycho-hygiene, memory training, and health education for the elderly, with group interventions. MATERIAL AND METHODS: A before and after community trial, with the administration of questionnaire with COOP/WONCA HRQoL charts to 200 participants. RESULTS: The study population (n=87), included those who completed the first and second questionnaire. Positive changes were seen in the overall before and after COOP/WONCA scores, with a mean change from 23.16 to 21.94, with statistical significance, p<=0.002. In the psychology groups, it changed from 28.14 to 23.57 with a p<=0.05, and healthy eating from 22.81 to 20.85, with p<=0.03. In the health education groups it changed from 21 to 20.81 points, and in memory training from 23.31 to 22.45 points (both without significance). CONCLUSIONS: The significant improvement in scores reflects a positive change in self-perceived health of this community after the intervention and proper operation of programs. The areas directly related to health and interventions in psychology and nutrition-exercise, are those with the most significant changes. PMID- 27353142 TI - Symptomatic Diverticulosis Is Characterized By Loose Stools. AB - BACKGROUND & AIMS: Symptomatic uncomplicated diverticular disease is considered to be a discreet clinical entity distinct from irritable bowel syndrome (IBS), but population-based data are unavailable. We aimed to investigate the prevalence and location of diverticulosis in the general population, and its association with colonic symptoms and mental health. We propose that individuals with diverticulosis would report more constipation and IBS. METHODS: We performed a population-based study of randomly selected adults born in Sweden (age, 18-70 y; 57.2% women); 745 received a gastroenterology consultation, completed validated abdominal symptom and mental health questionnaires, and were examined by colonoscopy. Logistic regression was used to calculate the associations between diverticulosis and age, sex, gastrointestinal symptoms, anxiety, depression, and self-rated health. RESULTS: Among the 742 participants (54.6% women), 130 (17.5%) had diverticulosis. Age was the strongest predictor of diverticulosis (P < .001), and diverticulosis was rare in participants younger than 40 years (0.7%). All participants with diverticulosis had sigmoid involvement. Participants with diverticulosis were more likely to report loose stools (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.20-2.96), urgency (OR, 1.64; 95% CI, 1.02-2.63), passing mucus (OR, 2.26; 95% CI, 1.08-4.72), and a high stool frequency (OR, 2.02; 95% CI, 1.11-3.65). Diverticulosis was associated with abdominal pain (OR, 2.10; 95% CI, 1.01-4.36; P = .047) and diarrhea-predominant IBS (OR, 9.55; 95% CI, 1.08-84.08; P = .04) in participants older than 60 years. The presence of anxiety and depression and self-rated health were similar in participants with and without diverticulosis. CONCLUSIONS: The prevalence of diverticulosis is age dependent. Diverticulosis is associated with diarrhea in subjects across all age ranges. In subjects older than age 60, diverticulosis is associated with abdominal pain and diarrhea-predominant IBS. PMID- 27353143 TI - Soot Combustion over Nanostructured Ceria with Different Morphologies. AB - In this study, nano-structure ceria with three different morphologies (nanorod, nanoparticle and flake) have been prepared by hydrothermal and solvothermal methods. The ceria samples were deeply characterized by XRD, SEM, TEM, H2-TPR, XPS and in-situ DRIFTS, and tested for soot combustion in absence/presence NO atmospheres under loose and tight contact conditions. The prepared ceria samples exhibit excellent catalytic activities, especially, the CeO2 with nanorod (Ce-R) shows the best catalytic activity, for which the peak temperature of soot combustion (Tm) is about 500 and 368 degrees C in loose and tight contact conditions, respectively. The catalytic activity for Ce-R is higher than that of the reported CeO2 catalysts and reaches a level that of precious metals. The characterization results reveal that the maximal amounts of adsorbed oxygen species on the surface of the nanostructure Ce-R catalyst should be the crucial role to decide the catalytic soot performance. High BET surface area may also be a positive effect on soot oxidation activity under loose contact conditions. PMID- 27353145 TI - Restrictive Cardiomyopathy Associated With Long-Term Use of Hydroxychloroquine for Systemic Lupus Erythematosus. AB - Hydroxychloroquine (HQ) is commonly prescribed for autoimmune diseases such as systemic lupus erythematosus. We report a case of a 75-year-old female presenting with de novo decompensated heart failure and restrictive cardiomyopathy (left ventricular ejection fraction: 40%-45%) after treatment with HQ for more than 11 years. Hydroxychloroquine was discontinued, and follow-up echocardiogram 57 days after discontinuation showed normalization of her left ventricular ejection fraction. A score of 7 on the Naranjo Adverse Drug Reaction Probability Scale indicates that HQ is a probable cause of this patient's cardiomyopathy. An adverse drug effect due to HQ should be considered in treated patients who present with restrictive cardiomyopathy. Discontinuation may allow for partial or complete reversal of the cardiomyopathy. PMID- 27353144 TI - FolC2-mediated folate metabolism contributes to suppression of inflammation by probiotic Lactobacillus reuteri. AB - Bacterial-derived compounds from the intestinal microbiome modulate host mucosal immunity. Identification and mechanistic studies of these compounds provide insights into host-microbial mutualism. Specific Lactobacillus reuteri strains suppress production of the proinflammatory cytokine, tumor necrosis factor (TNF), and are protective in a mouse model of colitis. Human-derived L. reuteri strain ATCC PTA 6475 suppresses intestinal inflammation and produces 5,10 methenyltetrahydrofolic acid polyglutamates. Insertional mutagenesis identified the bifunctional dihydrofolate synthase/folylpolyglutamate synthase type 2 (folC2) gene as essential for 5,10-methenyltetrahydrofolic acid polyglutamate biosynthesis, as well as for suppression of TNF production by activated human monocytes, and for the anti-inflammatory effect of L. reuteri 6475 in a trinitrobenzene sulfonic acid-induced mouse model of acute colitis. In contrast, folC encodes the enzyme responsible for folate polyglutamylation but does not impact TNF suppression by L. reuteri. Comparative transcriptomics between wild type and mutant L. reuteri strains revealed additional genes involved in immunomodulation, including previously identified hdc genes involved in histidine to histamine conversion. The folC2 mutant yielded diminished hdc gene cluster expression and diminished histamine production, suggesting a link between folate and histadine/histamine metabolism. The identification of genes and gene networks regulating production of bacterial-derived immunoregulatory molecules may lead to improved anti-inflammatory strategies for digestive diseases. PMID- 27353146 TI - Expression and purification of the modification-dependent restriction enzyme BisI and its homologous enzymes. AB - The methylation-dependent restriction endonuclease (REase) BisI (G(m5)C ? NGC) is found in Bacillus subtilis T30. We expressed and purified the BisI endonuclease and 34 BisI homologs identified in bacterial genomes. 23 of these BisI homologs are active based on digestion of (m5)C-modified substrates. Two major specificities were found among these BisI family enzymes: Group I enzymes cut GCNGC containing two to four (m5)C in the two strands, or hemi-methylated sites containing two (m5)C in one strand; Group II enzymes only cut GCNGC sites containing three to four (m5)C, while one enzyme requires all four cytosines to be modified for cleavage. Another homolog, Esp638I cleaves GCS ? SGC (relaxed specificity RCN ? NGY, containing at least four (m5)C). Two BisI homologs show degenerate specificity cleaving unmodified DNA. Many homologs are small proteins ranging from 150 to 190 amino acid (aa) residues, but some homologs associated with mobile genetic elements are larger and contain an extra C-terminal domain. More than 156 BisI homologs are found in >60 bacterial genera, indicating that these enzymes are widespread in bacteria. They may play an important biological function in restricting pre-modified phage DNA. PMID- 27353147 TI - EUROmediCAT signal detection: a systematic method for identifying potential teratogenic medication. AB - AIMS: Information about medication safety in pregnancy is inadequate. We aimed to develop a signal detection methodology to routinely identify unusual associations between medications and congenital anomalies using data collected by 15 European congenital anomaly registries. METHODS: EUROmediCAT database data for 14 950 malformed foetuses/babies with first trimester medication exposures in 1995-2011 were analyzed. The odds of a specific medication exposure (coded according to chemical substance or subgroup) for a specific anomaly were compared with the odds of that exposure for all other anomalies for 40 385 medication anomaly combinations in the data. Simes multiple testing procedure with a 50% false discovery rate (FDR) identified associations least likely to be due to chance and those associations with more than two cases with the exposure and the anomaly were selected for further investigation. The methodology was evaluated by considering the detection of well-known teratogens. RESULTS: The most common exposures were genitourinary system medications and sex hormones (35.2%), nervous system medications (28.0%) and anti-infectives for systemic use (25.7%). Fifty two specific medication anomaly associations were identified. After discarding 10 overlapping and three protective associations, 39 associations were selected for further investigation. These associations included 16 which concerned well established teratogens, valproic acid (2) and maternal diabetes represented by use of insulin (14). CONCLUSIONS: Medication exposure data in the EUROmediCAT central database can be analyzed systematically to determine a manageable set of associations for validation and then testing in independent datasets. Detection of teratogens depends on frequency of exposure, level of risk and teratogenic specificity. PMID- 27353148 TI - Failure to thrive in babies and toddlers. AB - Failure to thrive in a child is defined as 'lack of expected normal physical growth' or 'failure to gain weight'. Diagnosis requires repeated growth measurements over time using local, age-appropriate growth centile charts. Premature babies with appropriate growth velocity and children with 'catch-down' growth, constitutional growth delay or familial short stature show normal growth variants, and usually do not require further evaluation. In Singapore, the most common cause of failure to thrive in children is malnutrition secondary to psychosocial and caregiver factors. 'Picky eating' is common in the local setting and best managed with an authoritative feeding style from caregivers. Other causes are malabsorption and existing congenital or chronic medical conditions. Child neglect or abuse should always be ruled out. Iron deficiency is the most common complication. The family doctor plays a pivotal role in early detection, timely treatment, appropriate referrals and close monitoring of 'catch-up' growth in these children. PMID- 27353150 TI - Role of ion-pair states in the predissociation dynamics of Rydberg states of molecular iodine. AB - Using femtosecond pump-probe ion imaging spectroscopy, we establish the key role of I(+) + I(-) ion-pair (IP) states in the predissociation dynamics of molecular iodine I2 excited to Rydberg states. Two-photon excitation of Rydberg states lying above the lowest IP state dissociation threshold (1st tier) is found to be followed by direct parallel transitions into IP states of the 1st tier asymptotically correlating to a pair of I ions in their lowest states I(+)((3)P2) + I(-)((1)S0), of the 2nd tier correlating to I(+)((3)P0) + I(-)((1)S0), and of the 3rd tier correlating to I(+)((1)D2) + I(-)((1)S0). Predissociation via the 1st tier proceeds presumably with a delay of 1.6-1.7 ps which is close to the vibrational period in the 3rd tier state (3rd tier-mediated process). The 2nd tier IP state is concluded to be the main precursor for predissociation via lower lying Rydberg states proceeding with a characteristic time of 7-8 ps and giving rise to Rydberg atoms I(5s(2)5p(4)6s(1)). The channel generating I((2)P3/2) + I((2)P1/2) atoms with total kinetic energy corresponding to one-photon excitation is found to proceed via a pump - dump mechanism with dramatic change of angular anisotropy of this channel as compared with earlier nanosecond experiments. PMID- 27353149 TI - A multi-level intervention in subsidized housing sites to increase fruit and vegetable access and intake: Rationale, design and methods of the 'Live Well, Viva Bien' cluster randomized trial. AB - BACKGROUND: Adequate fruit and vegetable (F&V) intake is important for disease prevention. Yet, most Americans, especially low-income and racial/ethnic minorities, do not eat adequate amounts. These disparities are partly attributable to food environments in low-income neighborhoods where residents often have limited access to affordable, healthful food and easy access to inexpensive, unhealthful foods. Increasing access to affordable healthful food in underserved neighborhoods through mobile markets is a promising, year-round strategy for improving dietary behaviors and reducing F&V intake disparities. However, to date, there have been no randomized controlled trials studying their effectiveness. The objective of the 'Live Well, Viva Bien' (LWVB) cluster randomized controlled trial is to evaluate the efficacy of a multicomponent mobile market intervention at increasing F&V intake among residents of subsidized housing complexes. METHODS/DESIGN: One housing complex served as a pilot site for the intervention group and the remaining 14 demographically-matched sites were randomized into either the intervention or control group. The intervention group received bimonthly, discount, mobile, fresh F&V markets in conjunction with a nutrition education intervention (two F&V campaigns, newsletters, DVDs and cooking demonstrations) for 12 months. The control group received physical activity and stress reduction interventions. Outcome measures include F&V intake (measured by two validated F&V screeners at baseline, six-month and twelve months) along with potential psychosocial mediating variables. Extensive quantitative and qualitative process evaluation was also conducted throughout the study. DISCUSSION: Modifying neighborhood food environments in ways that increase access to affordable, healthful food is a promising strategy for improving dietary behaviors among low-income, racial and ethnic minority groups at increased risk for obesity and other food-related chronic diseases. Discount, mobile F&V markets address all the major barriers to eating more F&V (high cost, poor quality, limited access and limited time to shop and cook) and provide a year-round solution to limited access to healthful food in low-income neighborhoods. LWVB is the first randomized controlled trial evaluating the effectiveness of mobile markets at increasing F&V intake. If proven efficacious at increasing F&V consumption, LWVB could be disseminated widely to neighborhoods that have low access to fresh F&V. TRIALS REGISTRATION: Clinicatrials.gov registration number: NCT02669472 First Received: January 19, 2016. PMID- 27353152 TI - [Recurrent pulmonary embolism due to popliteal venous aneurysm]. AB - BACKGROUND: Popliteal venous aneurysms are very rare, but when left untreated they can lead to severe and recurrent pulmonary embolism. CASE DESCRIPTION: A 35 year-old man was referred to the outpatients' vascular clinic for additional diagnostics of a swelling just above the back of his right knee. He had a history of recurrent idiopathic pulmonary embolism despite anticoagulation. Diagnostic imaging revealed a large popliteal venous aneurysm. The patient underwent surgical resection of the aneurysm and was prescribed oral anticoagulation postoperatively. Duplex ultrasound at 3 months postoperative revealed unimpeded blood flow in the venous interposition graft. The patient no longer had oedema. CONCLUSION: Aneurysms of the popliteal vein should be included in the differential diagnosis of patients with pulmonary embolism. In patients with unexplained recurrent pulmonary embolism despite anticoagulation, additional diagnostic imaging of the lower extremities should be considered and inclusion of duplex ultrasound is recommended. PMID- 27353151 TI - High-throughput sequencing reveals differential regulation of miRNAs in fenoxaprop-P-ethyl-resistant Beckmannia syzigachne. AB - Non-target site resistance (NTSR) to herbicides is an increasing concern for weed control. The majority of previous studies have focused on metabolic resistance mechanisms of NTSR, but no research exists on gene regulation mechanisms behind herbicide resistance, such as microRNA (miRNA). Here, we identified 3 American sloughgrass (Beckmannia syzigachne Steud.) populations containing fenoxaprop-P ethyl-resistant plants. We then constructed small RNA libraries and subjected them to deep sequencing and bioinformatics analyses. Forty known and 36 potentially novel, predicted miRNAs were successfully identified. Of these, we identified 3 conserved, predicted candidate NTSR-determinant miRNAs and their potential corresponding target genes, as well as 4 novel potential miRNAs with high count. Target gene prediction and annotation indicated that these 7 differentially expressed miRNAs potentially play a role in regulating specific stress-responsive genes, very likely related to herbicide resistance. Expression profiles were determined with quantitative real-time PCR. The present study is a novel, large-scale characterization of weed miRNAs. The results should further our understanding of miRNA expression profiles associated with herbicide resistance, allowing for the development of more effective weed management strategies. PMID- 27353153 TI - [A young man with a painful knee]. AB - A 23-year-old man injured his left knee. A CT scan showed a dislocation of the proximal tibiofibular joint. Closed reduction of the dislocation was done successfully under procedural sedation and analgesia. Afterwards he was treated with a pressure bandage and immobilisation of the knee for 2 weeks. PMID- 27353154 TI - [Mesenteric venous thrombosis during pregnancy; a rare cause of acute ischaemia of the small intestine]. AB - BACKGROUND: Acute ischaemia of the small intestine is caused by mesenteric venous thrombosis in 5-15% of patients. The non-specific symptoms frequently lead to a diagnostic delay. CASE DESCRIPTION: A 30-year-old pregnant woman presented at the accident and emergency department with progressive abdominal pain, nausea and vomiting. During admission the patient developed signs of peritonitis. Diagnostic laparoscopy revealed a picture of mesenteric venous thrombosis, and we resected 170 cm ischemic small intestine. No underlying cause was identified, apart from the pregnancy. The patient was treated with low-molecular-weight heparin and later gave birth to a healthy child. CONCLUSION: If a patient presents with (unexplained) progressive abdominal symptoms and disproportional abdominal pain without peritonitis, the possibility of intestinal ischaemia should be considered during differential diagnosis. PMID- 27353155 TI - [A man with skin lesions of his face]. AB - A 69-year-old man with rheumatoid arthritis developed a discoid rash on his face years after the initiation of treatment with adalimumab. Serological tests were positive for antinuclear antibodies (ANA) and autoantibodies against Sjogren's syndrome-related antigen A (SSA). We diagnosed him with 'lupus-like syndrome'. After discontinuation of the adalimumab therapy and the use of topical corticosteroids, his symptoms resolved quickly. PMID- 27353156 TI - [PTSD in young children after medical procedure]. AB - An eight-year-old boy with spastic type bilateral cerebral palsy and a two-year old girl with biliary atresia were referred to a psycho-trauma centre. Both children developed post-traumatic stress disorder (PTSD) symptoms as a result of the medical procedure. Because of their symptoms, they were resisting further medical treatment. The children were given trauma-focused treatment (eye movement and desensitisation reprocessing and cognitive behavioural therapy). This article argues that hypnosis and distraction can play a role in preventing PTSD symptoms after undergoing a medical procedure. If PTSD is unavoidable, it is important to recognise the symptoms and to treat these children. Furthermore, their parents might also be traumatised. PTSD symptoms in children and their parents can be successfully treated. Also children with sub-threshold PTSD can benefit from trauma treatment. PMID- 27353157 TI - [A man with remarkable clavicles]. AB - A 26-year-old male complained of painful clavicles. His medical history included multiple fractures of both clavicles, all treated conservatively. Conventional radiographs revealed a typical shape of both clavicles, suggesting non-union. His extraordinary medical history and non-union of both clavicles led to the diagnosis: 'congenital pseudarthrosis of both clavicles'. PMID- 27353158 TI - [Electrotherapy for headaches]. AB - Neuromodulation is being applied increasingly for the treatment of drug resistant headache. Although these techniques are often considered high-tech, electrotherapy for headache has a long history; electric fish have been used for headache treatment since the first century CE. During the eighteenth and nineteenth century, static electricity was a treatment for a wide variety of neuropsychiatric disorders including headache. The efficacy of electrotherapy, however, has been disputed continuously, since opponents were of the opinion that the positive results could be attributed to suggestion. At the beginning of the twentieth century, the electric treatment of headache gradually disappeared. In recent years, there has been a resurgence in the use of electrotherapy, along with the efficacy debate. With this historical review we wish to emphasize the importance of placebo-controlled studies, not only in terms of electrotherapy of headache, but also for the evaluation of neuromodulation for other disorders. PMID- 27353159 TI - [Radiofrequency ablation of a symptomatic benign thyroid nodule]. AB - Radiofrequency ablation (RFA) enables the ablation of selected tissue by means of heat. For the first time in the Netherlands, RFA is being used to treat patients with benign thyroid nodules. RFA is able to reduce the volume of a nodule that may be causing cosmetic complaints or problems due to mass effect. This avoids the need for surgery or treatment with radioactive iodine in this benign condition. The average reduction in size is 80% in the first year, leading to a considerable decrease in both symptomatic and cosmetic complaints. At Erasmus Medical Centre, Rotterdam, the Netherlands, this technique has been introduced in accordance with current guidelines, and it is expected that other centres of excellence will follow in implementing it. It is important that the initial experiences with this technique in the Netherlands in terms of effectiveness, risks and patient satisfaction should be monitored before RFA becomes routine treatment. PMID- 27353160 TI - [Free choice of doctor: patient's right or doctor's power?]. AB - This article outlines the historical development of the principle of patients' free choice of doctor in the Netherlands. Far from being the result of debates on patients' rights, this principle was used instead as an instrument by the medical profession to gain a foothold in the power relations between doctors and sickness funds back in the early 20th-century. This development created a medical power bloc that lasted for most of that century and forced sickness funds and private insurers to start organizing in this fashion too. Therefore, when the new market ideology of introducing competition in health care was introduced in 1987, the fields of health provision and insurance were already defined by a high degree of cartelization. These relations lingered even after the introduction of regulated competition in 2006. Knowledge of this history therefore leads to a better understanding of current debates and problems in the organization of Dutch health care. PMID- 27353161 TI - [Pain trajectories in early symptomatic knee osteoarthritis]. AB - DESIGN: Retrospective cohort study. METHOD: We obtained data for this study from the 'Cohort Hip and Cohort Knee' (CHECK) study. Participants who presented with knee osteoarthritis at baseline were included. We assessed baseline patient parameters such as demographics, anamnesis and physical examination measurements. Pain outcome measure was assessed annually using a numeric rating scale. Different pain trajectories were defined by latent class growth analysis. Multinomial logistic regression was used to calculate relative risk ratios. RESULTS: In total, 705 participants were included. Six distinct pain trajectories were identified with favourable and unfavourable courses. We found significant differences in baseline characteristics between the different pain trajectories, including BMI; symptom severity; and pain coping strategies. Higher BMI, lower education, presence of co-morbidities, higher activity limitation scores and joint space tenderness were more often associated with trajectories characterized by more pain at first presentation and pain progression. No association was found for baseline radiographic features. CONCLUSION: We defined six distinct pain trajectories in individuals with early symptomatic knee osteoarthritis. Our results can help physicians identify those patients that require more frequent monitoring compared patients for whom a watch-and-wait policy seems justifiable. In general practice, radiography does not provide added value to the follow-up of early symptomatic knee osteoarthritis patients. PMID- 27353162 TI - [Aspiration of water during underwater birth]. AB - BACKGROUND: Underwater birth is becoming increasingly popular because of the advantages for the mother. Women who deliver in this way feel less pain and therefore pain relief is less frequently needed during the delivery. But what seems to be forgotten is the fact that aspiration of water by the neonate could take place during an underwater birth, resulting in respiratory distress. CASE DESCRIPTION: A one-day-old neonate was admitted because of tachypnoea following underwater delivery at home. The respiratory rate of the neonate was one hundred breaths per minute without evident signs of dyspnoea. Chest radiography showed bilateral patches on the lungs consistent with aspiration of bathwater. After seven days of intravenous antibiotic treatment, the neonate recovered and could be discharged home. CONCLUSION: An underwater birth may cause respiratory problems in the neonate. If a pregnant woman wants to deliver under water, she should also be advised of the potential detrimental consequences for the neonate. PMID- 27353163 TI - Synthesis and biological evaluation of lipophilic teicoplanin pseudoaglycon derivatives containing a substituted triazole function. AB - A series of lipophilic teicoplanin pseudoaglycon derivatives, including alkyl-, aryl-, calixarene- and protected sugar-containing conjugates, were prepared using azide-alkyne click chemistry. Out of the conditions applied, the CuSO4-ascorbate reagent system proved to be more efficient than the Cu(I)I-Et3N-mediated reaction. Some of the new compounds have high in vitro activity against glycopeptide-resistant Gram-positive bacteria, including vanA-positive Enterococcus faecalis. A few of them also display promising in vitro anti influenza activity. PMID- 27353165 TI - Pyrazinone protease inhibitor metabolites from Photorhabdus luminescens. AB - Photorhabdus luminescens is a bioluminescent entomopathogenic bacterium that undergoes phenotypic variation and lives in mutualistic association with nematodes of the family Heterorhabditidae. The pair infects and kills insects, and during their coordinated lifecycle, the bacteria produce an assortment of specialized metabolites to regulate its mutualistic and pathogenic roles. As part of our search for new specialized metabolites from the Photorhabdus genus, we examined organic extracts from P. luminescens grown in an amino-acid-rich medium based on the free amino-acid levels found in the circulatory fluid of its common insect prey, the Galleria mellonella larva. Reversed-phase HPLC/UV/MS-guided fractionation of the culture extracts led to the identification of two new pyrazinone metabolites, lumizinones A (1) and B (2), together with two N-acetyl dipeptides (3 and 4). The lumizinones were produced only in the phenotypic variant associated with nematode development and insect pathogenesis. Their chemical structures were elucidated by analysis of 1D and 2D NMR and high resolution ESI-QTOF-MS spectral data. The absolute configurations of the amino acids in 3 and 4 were determined by Marfey's analysis. Compounds 1-4 were evaluated for their calpain protease inhibitory activity, and lumizinone A (1) showed inhibition with an IC50 (half-maximal inhibitory concentration) value of 3.9 MUm. PMID- 27353166 TI - In vitro susceptibility of beta-lactamase-producing carbapenem-resistant Enterobacteriaceae (CRE) to eravacycline. AB - Eravacycline is a novel, fully synthetic fluorocycline antibiotic of the tetracycline class being developed for the treatment of complicated urinary tract infections and complicated intra-abdominal infections. Eravacycline has activity against many key Gram-negative pathogens, including Enterobacteriaceae resistant to carbapenems, cephalosporins, fluoroquinolones and beta-lactam/beta-lactamase inhibitor combinations, including strains that are multidrug-resistant. Carbapenem-resistant Enterobacteriaceae (CRE) isolates from 2010 to 2013 (n=110) were characterized for carbapenemase genes by PCR and sequencing. MICs for eravacycline, tetracycline, tigecycline, amikacin, imipenem, ceftazidime, cefotaxime and levofloxacin were determined in broth microdilution assays. All isolates produced at least one carbapenemase, most frequently KPC-3. Nine isolates produced both a KPC serine carbapenemase and a metallo-beta-lactamase, NDM-1 (n=1) or VIM-1 (n=8). The 110 isolates were highly resistant to all the beta-lactams tested and to levofloxacin, and had MIC50/MIC90 values in the intermediate range for tetracycline and amikacin. MIC50/MIC90 values for eravacycline were 1/2 MUg ml(-1) compared with 2/2 MUg ml(-1) for tigecycline. Eravacycline MICs were often twofold lower than for tigecycline, with 64% of the eravacycline MICs <2 MUg ml(-1) as compared with <4% of tigecycline MICs. Overall, eravacycline demonstrated the lowest cumulative MICs against this panel of recent CRE and may have the potential to treat infections caused by CRE. PMID- 27353164 TI - Antibiotics in the clinical pipeline at the end of 2015. AB - There is growing global recognition that the continued emergence of multidrug resistant bacteria poses a serious threat to human health. Action plans released by the World Health Organization and governments of the UK and USA in particular recognize that discovering new antibiotics, particularly those with new modes of action, is one essential element required to avert future catastrophic pandemics. This review lists the 30 antibiotics and two beta-lactamase/beta-lactam combinations first launched since 2000, and analyzes in depth seven new antibiotics and two new beta-lactam/beta-lactamase inhibitor combinations launched since 2013. The development status, mode of action, spectra of activity and genesis (natural product, natural product-derived, synthetic or protein/mammalian peptide) of the 37 compounds and six beta-lactamase/beta-lactam combinations being evaluated in clinical trials between 2013 and 2015 are discussed. Compounds discontinued from clinical development since 2013 and new antibacterial pharmacophores are also reviewed. PMID- 27353167 TI - Isolation and anti-HIV-1 integrase activity of lentzeosides A-F from extremotolerant lentzea sp. H45, a strain isolated from a high-altitude Atacama Desert soil. AB - The extremotolerant isolate H45 was one of several actinomycetes isolated from a high-altitude Atacama Desert soil collected in northwest Chile. The isolate was identified as a new Lentzea sp. using a combination of chemotaxonomic, morphological and phylogenetic properties. Large scale fermentation of the strain in two different media followed by chromatographic purification led to the isolation of six new diene and monoene glycosides named lentzeosides A-F, together with the known compound (Z)-3-hexenyl glucoside. The structures of the new compounds were confirmed by HRESIMS and NMR analyses. Compounds 1-6 displayed moderate inhibitory activity against HIV integrase. PMID- 27353168 TI - Antibacterial fatty acids destabilize hydrophobic and multicellular aggregates of biofilm in S. aureus. AB - Present study is based on 20 methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered from different food items. These isolates were identified on the basis of colony morphology, Gram staining and growth on different selective and differential media. Studies on 16S RNA and positive reactions on DNase agar and Prolex Latex Agglutination system confirm it as Staphylococcus aureus. Oxacillin susceptibility testing and PCR with mecA gene-specific primer results showed that these isolates are MRSA-carrying mecA gene that belongs to SCCmecA type IV and also harbor agr type II. Phenotypic study revealed that these isolates adopt biofilm mode of growth after exposure to subinhibitory doses of oxacillin. The biofilm and cell surface hydrophobicity have a strong correlation. It was noticed that affinity to hexadecane (apolar-solvent) of planktonic cells was low, suggesting its hydrophilic character. However, as the cells are exposed to oxacillin, they adopt biofilm mode of life and the affinity to apolar solvent increases, indicating a hydrophobic character. In biofilm consortia, the cells with more hydrophobic surfaces show incomplete septation and produce multicellular aggregates. This is due to reduced expression of atl gene. This was confirmed by real-time PCR studies. Moreover, the planktonic or wild-type phenotypes of these isolates were more tolerant to antibacterial effect of the fatty acids used; that is, cis-2-decanoic acid and cis-9-octadectanoic acid. These fatty acids were more effective against biofilms. After exposure to these fatty acids, established biofilms were dispersed and surviving cells were unable to readopt biofilm mode of life. The planktonic or wild-type phenotypes produce fatty acid-modifying enzyme (FAME) to inactivate the bactericidal activity of fatty acids by esterification to cholesterol. The biofilm indwellers are metabolically inactive and unable to produce FAME; hence, they are vulnerable to antibiofilm effect of cis-2-decanoic acid and cis-9-octadectanoic acid. PMID- 27353169 TI - MiR-548an, Transcriptionally Downregulated by HIF1alpha/HDAC1, Suppresses Tumorigenesis of Pancreatic Cancer by Targeting Vimentin Expression. AB - Hypoxic microenvironments contribute to the tumorigenesis of numerous cancers by regulating the expression of a subset of miRNAs called "hypoxiamiRs." However, the function and mechanism of these deregulated miRNAs in hypoxic microenvironments within pancreatic cancers remain undefined. This study demonstrates that miR-548an is significantly downregulated in pancreatic cancer tissues and correlates with increased tumor size, advanced TNM stage, distant metastasis, and poor prognosis. Moreover, the overexpression of miR-548an significantly inhibited the proliferation and invasion of pancreatic cancer cells in vitro and in vivo We further revealed that hypoxia-induced factor-1alpha (HIF 1alpha) induces the downregulation of miR-548an in pancreatic cancer cells during hypoxia. Our co-IP and ChIP assays revealed that HIF-1alpha and histone deacetylase 1 (HDAC1) form a complex and bind to the hypoxia response elements (HRE) on the miR-548an promoter. In addition, inhibition of HDAC1 with trichostatin A antagonizes the suppression of miR-548 by hypoxia. Our dual luciferase assay validated that miR-548an directly binds to the 3' untranslated region of vimentin mRNA. The downregulation of vimentin suppresses the proliferation and invasion of pancreatic cancer cells in vitro and in vivo In addition, vimentin was inversely correlated with miR-548an expression in pancreatic cancer samples. In conclusion, our findings suggest that the HIF 1alpha-HDAC1 complex transcriptionally inhibits miR-548an expression during hypoxia, resulting in the upregulation of vimentin that facilitates the pancreatic tumorigenesis. Mol Cancer Ther; 15(9); 2209-19. (c)2016 AACR. PMID- 27353170 TI - A New Class of Bifunctional Major Histocompatibility Class I Antibody Fusion Molecules to Redirect CD8 T Cells. AB - Bifunctional antibody fusion proteins engaging effector T cells for targeted elimination of tumor cells via CD3 binding have shown efficacy in both preclinical and clinical studies. Different from such a polyclonal T-cell recruitment, an alternative concept is to engage only antigen-specific T-cell subsets. Recruitment of specific subsets of T cells may be as potent but potentially lead to fewer side effects. Tumor-targeted peptide-MHC class I complexes (pMHCI-IgGs) bearing known antigenic peptides complexed with MHC class I molecules mark tumor cells as antigenic and utilize the physiologic way to interact with and activate T-cell receptors. If, for example, virus-specific CD8(+) T cells are addressed, the associated strong antigenicity and tight immune surveillance of the effector cells could lead to efficacious antitumor treatment in various tissues. However, peptide-MHC class I fusions are difficult to express recombinantly, especially when fused to entire antibody molecules. Consequently, current formats are largely limited to small antibody fragment fusions expressed in bacteria followed by refolding or chemical conjugation. Here, we describe a new molecular format bearing a single pMHCI complex per IgG fusion molecule characterized by enhanced stability and expression yields. This molecular format can be expressed in a full immunoglobulin format and can be designed as mono- or bivalent antibody binders. Mol Cancer Ther; 15(9); 2130-42. (c)2016 AACR. PMID- 27353171 TI - Tunable tapered waveguide for efficient compression of light to graphene surface plasmons. AB - Dielectric-graphene-dielectric (DGD) structure has been widely used to construct optical devices at infrared region with features of small footprint and low energy dissipation. The optical properties of graphene can be manipulated by changing its chemical potential by applying a biased voltage onto graphene. However, the excitation efficiency of surface wave on graphene by end-fire method is very low because of large wavevector mismatch between infrared light and surface wave. In this paper, a dielectric-semiconductor-dielectric (DSD) tapered waveguide with magnetic tunability for efficient excitation of surface waves on DGD at infrared region is proposed and analyzed. Efficient excitation of surface waves on DGD with various chemical potentials in graphene layer and incident frequencies can be attained by merely changing the external magnetic field applied onto the DSD tapered waveguide. The electromagnetic simulations verify the design of the proposed structure. More importantly, the constituent materials used in the proposed structure are available in nature. This work opens the door toward various applications in the field of using surface waves. PMID- 27353172 TI - Urachal adenocarcinoma incidentally discovered in a young woman at elective caesarean section. AB - Urachal adenocarcinoma is a rare non-urothelial malignancy that represents only 0.5% of all vesical cancers. Urachal adenocarcinoma most commonly occurs in the 5th to 7th decade. We describe a case of a 35-year-old woman (G3P1) who presented at 20 weeks pregnancy with two episodes of post-coital bleeding. Ultrasound demonstrated a uterine mass measuring 59*43*56 mm, presumed to be a leiomyoma. The decision was made to proceed to caesarean section at 38 weeks, given the progression of the presumed leiomyoma. A 2 cm bladder dome mass was incidentally discovered at the time of the caesarean section and an urgent intraoperative urology consult was sought. Resultantly, the bladder mass was dissected to the dome, and pathology returned urachal adenocarcinoma. This case report considers the treatment decisions involved when faced with urachal adenocarcinoma and reviews the literature surrounding this rare malignancy. PMID- 27353173 TI - Skin necrosis after self-removal of an artificial penile nodule in a Surinamese man. AB - The implantation of objects in the penis for aesthetic reasons or sexual pleasure is becoming more popular among specific socioethnic groups within both, non Western and Western countries. The implantation and removal of penile implants is currently often performed unanaesthetised, and in unsterile conditions, putting men who undergo the practice at risk of complications. This paper describes a patient with an infection of the penis after self-removal of a penile implant, requiring urgent medical treatment. PMID- 27353174 TI - Simple vaginal trachelectomy as a fertility-sparing treatment to manage high grade dyskaryosis following multiple large loop excision of the transformation zone. AB - A 34-year-old nullipara, wishing to start a family, presented to colposcopy clinic. Her most recent cervical cytology result showed high-grade dyskaryosis. Having undergone four large loop excisions of the transformation zone during the past 6 years, this woman had no remaining vaginal cervix. In order to excise presumed high-grade cervical intraepithelial neoplasia while mitigating obstetric risk, she underwent a simple vaginal trachelectomy and isthmic cerclage. 6 months later, the patient had a negative test of cure. 7 months following surgery she became pregnant naturally. At 29 weeks she had antenatal sepsis of unknown cause, which was treated with intravenous antibiotics. She delivered by caesarean section at 37 weeks and now has a healthy child. This report will discuss the obstetric impact of colposcopic treatment, and simple vaginal trachelectomy as a fertility-sparing treatment option for women who have had multiple loop excision procedures to treat premalignant lesions. PMID- 27353175 TI - Type 1 Brugada pattern ECG due to supra-therapeutic phenytoin level. AB - Brugada syndrome is an inherited arrhythmogenic disease, characterised by a coved type ST segment elevation in right precordial leads and an increased risk of sudden cardiac death due to ventricular arrhythmia. To unmask or exacerbate a Brugada ECG pattern, class IA or IC antiarrhythmic agents are used, and clinicians can predict sudden cardiac death in a high-risk patient. However, phenytoin, one of the class IB agents, may induce a Brugada pattern ECG at a supra-therapeutic level and this association has rarely been reported. We describe a case of a patient with a phenytoin level about twice as high as the therapeutic level, which led to the emergence of a type 1 Brugada pattern ECG. Awareness should be made between this important association of supra-therapeutic phenytoin level and type 1 Brugada pattern ECG because symptomatic Brugada syndrome can lead to sudden cardiac death. PMID- 27353176 TI - Fungus ball in the nasal cavity mimicking a rhinolith. AB - A 63-year-old man presented to the outpatient department of our tertiary care hospital, with unilateral left nasal obstruction, foul smelling nasal discharge and occasional mild epistaxis. On examination, a hard greyish black mass was noted in the anteroinferior portion of the inferior turbinate, with extension posteriorly into the inferior meatus with surrounding unhealthy granulation tissue. Provisional diagnosis of rhinolith was surprisingly reversed by histopathology, which suggested the presence of an Aspergillus fungus ball with Actinomyces colonisation. PMID- 27353177 TI - Femoral diaphyseal stress fracture as the initial presentation of acute leukaemia in an adolescent. AB - A 14-year-old boy was referred to the orthopaedic clinic by his general practitioner, reporting of a 6-week history of left thigh pain. Clinical examination was unremarkable. Radiographs demonstrated a periosteal reaction at the proximal femur. MRI scans demonstrated a stress fracture of the femur, with no associated sinister features and no evidence of a pathological lesion. As the fracture healed and symptoms improved, the patient became unwell with weight loss, lethargy, chest and jaw pain and fevers. After multiple blood tests over a 25-day period, including five full blood counts and two normal blood films, a third blood film finally demonstrated blasts in keeping with acute leukaemia. We discuss a literature review of musculoskeletal manifestations of leukaemia and the often atypical presentations found. PMID- 27353178 TI - Acute pericarditis: a presenting manifestation of aortic dissection. PMID- 27353179 TI - Superior mesenteric artery syndrome: CT findings. PMID- 27353180 TI - Myxoedema coma: a forgotten presentation of extreme hypothyroidism. PMID- 27353181 TI - Overlapping lung parenchymal and bronchial lesion and hilar lymphadenopathy in pulmonary actinomycosis mimicking lung cancer. PMID- 27353182 TI - Near Full-Length Genome Identification of a Novel HIV-1 Recombinant Form (CRF01_AE/CRF07_BC) in Zhejiang, China. AB - CRF01_AE and CRF07_BC are the two major circulating recombinant forms (CRFs) in China. Furthermore, many kinds of unique recombinant forms (URFs) between CRF01_AE and CRF07_BC were recently identified in China. Here we detected a novel recombinant of CRF07_BC/CRF01_AE, whose genome structure is distinctly different from other URFs reported before. The phylogenetic analysis of the near full length sequence of 15zj032 reveals that three regions of CRF01_AE insert into the CRF07_BC backbone. Recently, the continued emergence of novel URFs implies that super infections of different subtypes of HIV-1 are common in China and should be given enough importance. PMID- 27353183 TI - US Supreme Court strikes down key provisions of restrictive Texas abortion law. PMID- 27353184 TI - Full-length genome analysis of two genetically distinct variants of porcine epidemic diarrhea virus in Thailand. AB - Porcine epidemic diarrhea virus (PEDV) has continued to cause sporadic outbreaks in Thailand since 2007 and a pandemic variant containing an insertion and deletion in the spike gene was responsible for outbreaks. In 2014, there were further outbreaks of the disease occurring within four months of each other. In this study, the full-length genome sequences of two genetically distinct PEDV isolates from the outbreaks were characterized. The two PEDV isolates, CBR1/2014 and EAS1/2014, were 28,039 and 28,033 nucleotides in length and showed 96.2% and 93.6% similarities at nucleotide and amino acid levels respectively. In total, we have observed 1048 nucleotide substitutions throughout the genome. Compared to EAS1/2014, CBR1/2014 has 2 insertions of 4 ((56)GENQ(59)) and 1 ((140)N) amino acid positions 56-59 and 140, and 2 deletions of 2 ((160)DG(161)) and 1 ((1199)Y) amino acid positions 160-161 and 1199. The phylogenetic analysis based on full length genome of CBR1/2014 isolate has grouped the virus with the pandemic variants. In contrast, EAS1/2014 isolate was grouped with CV777, LZC and SM98, a classical variant. Our findings demonstrated the emergence of EAS1/2014, a classical variant which is novel to Thailand and genetically distinct from the currently circulating endemic variants. This study warrants further investigations into molecular epidemiology and genetic evolution of the PEDV in Thailand. PMID- 27353185 TI - Differences among HIV-1 subtypes in drug resistance against integrase inhibitors. AB - Three integrase strand transfer inhibitors (INSTIs), raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG), have been approved by the FDA. Resistance against these three INSTIs have been reported and cross-resistance among them has been documented. Due to extensive and dynamic genetic diversity in different HIV-1 variants, significant differences in susceptibility to the INSTIs have been observed among HIV subtypes. This review summarizes what is known about this topic and discusses possible clinical implications. PMID- 27353187 TI - Drug company is suspended from UK industry body after "deception on a grand scale". PMID- 27353186 TI - Whole genome sequences of Japanese porcine species C rotaviruses reveal a high diversity of genotypes of individual genes and will contribute to a comprehensive, generally accepted classification system. AB - Porcine rotavirus C (RVC) is distributed throughout the world and is thought to be a pathogenic agent of diarrhea in piglets. Although, the VP7, VP4, and VP6 gene sequences of Japanese porcine RVCs are currently available, there is no whole-genome sequence data of Japanese RVC. Furthermore, only one to three sequences are available for porcine RVC VP1-VP3 and NSP1-NSP3 genes. Therefore, we determined nearly full-length whole-genome sequences of nine Japanese porcine RVCs from seven piglets with diarrhea and two healthy pigs and compared them with published RVC sequences from a database. The VP7 genes of two Japanese RVCs from healthy pigs were highly divergent from other known RVC strains and were provisionally classified as G12 and G13 based on the 86% nucleotide identity cut off value. Pairwise sequence identity calculations and phylogenetic analyses revealed that candidate novel genotypes of porcine Japanese RVC were identified in the NSP1, NSP2 and NSP3 encoding genes, respectively. Furthermore, VP3 of Japanese porcine RVCs was shown to be closely related to human RVCs, suggesting a gene reassortment event between porcine and human RVCs and past interspecies transmission. The present study demonstrated that porcine RVCs show greater genetic diversity among strains than human and bovine RVCs. PMID- 27353188 TI - Genetic and functional analyses of krs, a locus encoding kurstakin, a lipopeptide produced by Bacillus thuringiensis. AB - Bacteria of the Bacillus genus are able to synthesize several families of lipopeptides. These small molecules are the product of non-ribosomal peptide synthetases. In 2000, it was found that Bacillus thuringiensis, an entomopathogenic bacterium of the Bacillus cereus group, produced a previously unknown lipopeptide: kurstakin. Genomic analyses reveal that the krs locus, encoding the kurstakin synthetases, is specific to the B. cereus group, but is unevenly distributed within this group. Previous work showed that krs transcription requires the necrotrophism quorum-sensor NprR. Here, we demonstrated that the genes of the krs locus form an operon and we defined its transcription start site. Following krs transcription at the population and single-cell levels in multiple culture conditions, we depicted a condition dependent transcription pattern, indicating that production of kurstakin is subject to environmental regulation. Consistent with this idea, we found krs transcription to be regulated by another master regulator, Spo0A, suggesting that krs expression is fine-tuned by integrating multiple signals. We also reported an unknown DNA palindrome in the krs promoter region that modulates krs expression. Due to their surfactant properties, lipopeptides could play several physiological roles. We showed that the krs locus was required for proper biofilm structuration. PMID- 27353190 TI - Shark teeth as edged weapons: serrated teeth of three species of selachians. AB - Prior to European contact, South Pacific islanders used serrated shark teeth as components of tools and weapons. They did this because serrated shark teeth are remarkably effective at slicing through soft tissues. To understand more about the forms and functions of serrated shark teeth, we examined the morphology and histology of tooth serrations in three species: the Tiger Shark (Galeocerdo cuvier), Blue Shark (Prionace glauca), and White Shark (Carcharodon carcharias). We show that there are two basic types of serrations. A primary serration consists of three layers of enameloid with underlying dentine filling the serration's base. All three species studied have primary serrations, although the dentine component differs (orthodentine in Tiger and Blue Sharks; osteodentine in the White Shark). Smaller secondary serrations are found in the Tiger Shark, formed solely by enameloid with no contribution from underlying dentine. Secondary serrations are effectively "serrations within serrations" that allow teeth to cut at different scales. We propose that the cutting edges of Tiger Shark teeth, equipped with serrations at different scales, are linked to a diet that includes large, hard-shelled prey (e.g., sea turtles) as well as smaller, softer prey such as fishes. We discuss other aspects of serration form and function by making analogies to man-made cutting implements, such as knives and saws. PMID- 27353189 TI - HIV viraemia and mother-to-child transmission risk after antiretroviral therapy initiation in pregnancy in Cape Town, South Africa. AB - OBJECTIVES: Maternal HIV viral load (VL) drives mother-to-child HIV transmission (MTCT) risk but there are few data from sub-Saharan Africa, where most MTCT occurs. We investigated VL changes during pregnancy and MTCT following antiretroviral therapy (ART) initiation in Cape Town, South Africa. METHODS: We conducted a prospective study of HIV-infected women initiating ART within routine antenatal services in a primary care setting. VL measurements were taken before ART initiation and up to three more times within 7 days postpartum. Analyses examined VL changes over time, viral suppression (VS) at delivery, and early MTCT based on polymerase chain reaction (PCR) testing up to 8 weeks of age. RESULTS: A total of 620 ART-eligible HIV-infected pregnant women initiated ART, with 2425 VL measurements by delivery (median gestation at initiation, 20 weeks; median pre ART VL, 4.0 log10 HIV-1 RNA copies/mL; median time on ART before delivery, 118 days). At delivery, 91% and 73% of women had VL <= 1000 and <= 50 copies/mL, respectively. VS was strongly predicted by time on therapy and pre-ART VL. The risk of early MTCT was strongly associated with delivery VL, with risks of 0.25, 2.0 and 8.5% among women with VL < 50, 50-1000 and > 1000 copies/mL at delivery, respectively (P < 0.001). CONCLUSIONS: High rates of VS at delivery and low rates of MTCT can be achieved in a routine care setting in sub-Saharan Africa, indicating the effectiveness of currently recommended ART regimens. Women initiating ART late in pregnancy and with high VL appear substantially less likely to achieve VS and require targeted research and programmatic attention. PMID- 27353191 TI - Breeding biology of a winter-breeding procellariiform in the North Atlantic, the Macaronesian shearwater Puffinus lherminieri baroli. AB - The breeding success of burrow-nesting seabirds may be influenced by both nest site characteristics and oceanographic conditions influencing food availability at sea. In this study we describe the breeding biology of the winter-breeding Macaronesian shearwater (Puffinus lherminieri baroli), including nest site characteristics and interspecific competition. We also evaluate the possible effects of changing oceanographic conditions on breeding phenology and breeding success. The study was carried out over two breeding seasons on two islands in the North Atlantic Ocean, Cima Islet and Selvagem Grande. Oceanographic characteristics differed between years. On a regional scale, the North Atlantic Oscillation (NAO) index was low and negative in 2011, and on a local scale, birds used areas with significantly lower values of chlorophyll a concentration and significantly higher values of sea surface temperature anomalies. Hatching success was higher in 2012 than in 2011. At both colonies, egg cracking was the main cause of hatching failure, but in 2011 several eggs on Selvagem Grande were deserted. In 2012 birds laid earlier and chicks had longer wings and were heavier. At both colonies, nests that were deeper, were sheltered from prevailing winds and had small chambers and a soil substrate had a higher probability of being used successfully by the birds. Nests occupied solely by Macaronesian shearwaters were much deeper and had less volume than nests shared with other species. Our study suggests that the breeding success of Macaronesian shearwaters is strongly related to nest site characteristics and that at-sea environmental conditions exert a strong influence on reproductive parameters, with birds breeding in a poor year (evaluated in terms of lower marine productivity) laying much later and their chicks growing at a slower rate than in a good year. The influence of nest site characteristics and environmental conditions may be very important for understanding the breeding ecology of Procellariiformes and may help explain the negative population trend of Macaronesian shearwaters. PMID- 27353193 TI - Upper gastrointestinal bleeding (watermelon stomach) in a patient with limited scleroderma (CREST syndrome). PMID- 27353192 TI - From orphan drugs to adopted therapies: Advancing C3-targeted intervention to the clinical stage. AB - Complement dysregulation is increasingly recognized as an important pathogenic driver in a number of clinical disorders. Complement-triggered pathways intertwine with key inflammatory and tissue destructive processes that can either increase the risk of disease or exacerbate pathology in acute or chronic conditions. The launch of the first complement-targeted drugs in the clinic has undeniably stirred the field of complement therapeutic design, providing new insights into complement's contribution to disease pathogenesis and also helping to leverage a more personalized, comprehensive approach to patient management. In this regard, a rapidly expanding toolbox of complement therapeutics is being developed to address unmet clinical needs in several immune-mediated and inflammatory diseases. Elegant approaches employing both surface-directed and fluid-phase inhibitors have exploited diverse components of the complement cascade as putative points of therapeutic intervention. Targeting C3, the central hub of the system, has proven to be a promising strategy for developing biologics as well as small-molecule inhibitors with clinical potential. Complement modulation at the level of C3 has recently shown promise in preclinical primate models, opening up new avenues for therapeutic intervention in both acute and chronic indications fueled by uncontrolled C3 turnover. This review highlights recent developments in the field of complement therapeutics, focusing on C3 directed inhibitors and alternative pathway (AP) regulator-based approaches. Translational perspectives and considerations are discussed, particularly with regard to the structure-guided drug optimization and clinical advancement of a new generation of C3-targeted peptidic inhibitors. PMID- 27353194 TI - Tactile feedback for relief of deafferentation pain using virtual reality system: a pilot study. AB - BACKGROUND: Previous studies have tried to relieve deafferentation pain (DP) by using virtual reality rehabilitation systems. However, the effectiveness of multimodal sensory feedback was not validated. The objective of this study is to relieve DP by neurorehabilitation using a virtual reality system with multimodal sensory feedback and to validate the efficacy of tactile feedback on immediate pain reduction. METHODS: We have developed a virtual reality rehabilitation system with multimodal sensory feedback and applied it to seven patients with DP caused by brachial plexus avulsion or arm amputation. The patients executed a reaching task using the virtual phantom limb manipulated by their real intact limb. The reaching task was conducted under two conditions: one with tactile feedback on the intact hand and one without. The pain intensity was evaluated through a questionnaire. RESULTS: We found that the task with the tactile feedback reduced DP more (41.8 +/- 19.8 %) than the task without the tactile feedback (28.2 +/- 29.5 %), which was supported by a Wilcoxon signed-rank test result (p < 0.05). CONCLUSIONS: Overall, our findings indicate that the tactile feedback improves the immediate pain intensity through rehabilitation using our virtual reality system. PMID- 27353195 TI - Here Comes the Sunshine: Industry's Payments to Cardiothoracic Surgeons. AB - BACKGROUND: The Physician Payment Sunshine Act was implemented to provide transparency to financial transactions between industry and physicians. Under this law, the Open Payments Program (OPP) was created to publicly disclose all transactions and inform patients of potential conflicts of interest. Collaboration between industry and cardiothoracic surgeon-scientists is essential in developing new approaches to treating patients with cardiac disease. The objective of this study is to characterize industry payments to cardiothoracic surgeons as reported by the OPP. METHODS: We used the first wave of Physician Payment Sunshine Act data (August 2013 to December 2013) to assess industry payments made to cardiothoracic surgeons. RESULTS: Cardiothoracic surgeons (n = 2,495) received a total of $4,417,545 during a 5-month period. Cardiothoracic surgeons comprised 0.5% of all persons in the OPP and received 0.9% of total disclosed industry funding. Among cardiothoracic surgeons receiving funding, 34% received payments less than $100, 43% received payments of $100 to $999, 19% received payments of $1,000 to $9,999, 4% received payments of $10,000 to $99,999, and 0.2% received payments of more than $100,000. The median was $181 (interquartile range [IQR]: $60 to $843) and the mean +/- SD was $1,771 +/- $7,664. The largest payment to an individual surgeon was $159,444. The three largest median payments made to cardiothoracic surgeons by expense category were royalty fees $8,398 (IQR: $536 to $12,316), speaker fees $3,600 (IQR: $1,500 to $8,000), and honoraria $3,344 (IQR: $1,563 to $7,350). CONCLUSIONS: Among cardiothoracic surgeons who are listed as recipients of nonresearch industry payments, 50% of cardiothoracic surgeons received less than $181. Awareness of the OPP data is critical for cardiothoracic surgeons, as it provides a means to prevent potential public misconceptions about industry payments within the specialty that may affect patient trust. PMID- 27353196 TI - Tick-Borne Relapsing Fever in Dogs. AB - BACKGROUND: In the United States, Tick-Borne Relapsing Fever (TBRF) in dogs is caused by the spirochete bacteria Borrelia turicatae and Borrelia hermsii, transmitted by Ornithodoros spp. ticks. The hallmark diagnostic feature of this infection is the visualization of numerous spirochetes during standard blood smear examination. Although the course of spirochetemia has not been fully characterized in dogs, in humans infected with TBRF the episodes of spirochetemia and fever are intermittent. OBJECTIVES: To describe TBRF in dogs by providing additional case reports and reviewing the disease in veterinary and human medicine. ANIMALS: Five cases of privately-owned dogs naturally infected with TBRF in Texas are reviewed. METHODS: Case series and literature review. RESULTS: All dogs were examined because of lethargy, inappetence, and pyrexia. Two dogs also had signs of neurologic disease. All dogs had thrombocytopenia and spirochetemia. All cases were administered tetracyclines orally. Platelet numbers improved and spirochetemia and pyrexia resolved in 4 out of 5 dogs, where follow up information was available. CONCLUSION AND CLINICAL IMPORTANCE: TBRF is likely underdiagnosed in veterinary medicine. In areas endemic to Ornithodoros spp. ticks, TBRF should be considered in dogs with thrombocytopenia. Examination of standard blood smears can provide a rapid and specific diagnosis of TBRF when spirochetes are observed. PMID- 27353197 TI - Local adaptation to developmental density does not lead to higher mating success in Drosophila melanogaster. AB - In this study, we investigate the effect of local adaptation to developmental density on male mating success in laboratory populations of Drosophila melanogaster. Mating success is known to be influenced by body condition which can in turn be influenced by local adaptation. We test the hypothesis that males adapted to a given environment have higher mating success when assayed in that environment. We used males selected for adaptation to high larval density and their controls which are reared at low larval density. We grew assay males in low and high densities whereas the focal females (raised at low larval density) used for the experiment belonged to the common ancestor of selected and control populations. We considered selected males grown at high density and control males grown at low density as 'adapted'. Similarly, we considered selected males grown at low density and control males grown at high density as 'nonadapted'. Selected male belonging to a given treatment (larval density) was made to compete with control male of the same treatment for mating with ancestral female. We quantified components of reproductive fitness: mating latency, copulation duration, mating success and number of progeny sired by the 'adapted' and 'nonadapted' males. The results show that local adaptation does not lead to higher mating success in populations adapted to their own larval rearing environment. PMID- 27353198 TI - Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms. AB - Background: Acetaminophen is extensively used during pregnancy. But there is a lack of population-representative cohort studies evaluating its effects on a range of neuropsychological and behavioural endpoints. We aimed to assess whether prenatal exposure to acetaminophen is adversely associated with neurodevelopmental outcomes at 1 and 5 years of age. Methods: This Spanish birth cohort study included 2644 mother-child pairs recruited during pregnancy. The proportion of liveborn participants evaluated at 1 and 5 years was 88.8% and 79.9%, respectively. Use of acetaminophen was evaluated prospectively in two structured interviews. Ever/never use and frequency of use (never, sporadic, persistent) were measured. Main neurodevelopment outcomes were assessed using Childhood Autism Spectrum Test (CAST), Conner's Kiddie Continuous Performance Test (K-CPT) and ADHD-DSM-IV form list. Regression models were adjusted for social determinants and co-morbidities. Results: Over 40% of mothers reported using acetaminophen. Ever-exposed offspring had higher risks of presenting more hyperactivity/impulsivity symptoms [incidence rate ratio (IRR) = 1.41, 95% confidence interval (CI) 1.01-1.98), K-CPT commission errors (IRR = 1.10, 1.03 1.17), and lower detectability scores (coefficient beta = -0.75, -0.13--0.02). CAST scores were increased in ever-exposed males (beta = 0.63, 0.09-1.18). Increased effect sizes of risks by frequency of use were observed for hyperactivity/impulsivity symptoms (IRR = 2.01, 0.95-4.24) in all children, K-CPT commission errors (IRR = 1.32, 1.05-1.66) and detectability (beta = -0.18, -0.36 0.00) in females, and CAST scores in males (beta = 1.91, 0.44-3.38). Conclusions: Prenatal acetaminophen exposure was associated with a greater number of autism spectrum symptoms in males and showed adverse effects on attention-related outcomes for both genders. These associations seem to be dependent on the frequency of exposure. PMID- 27353200 TI - Low Cost Inkjet Printed Smart Bandage for Wireless Monitoring of Chronic Wounds. AB - Chronic wounds affect millions of patients around the world and their treatment is challenging as the early signs indicating their development are subtle. In addition, a type of chronic wound, known as pressure ulcer, develops in patients with limited mobility. Infection and frequent bleeding are indicators of chronic wound development. In this article, we present an unprecedented low cost continuous wireless monitoring system, realized through inkjet printing on a standard bandage, which can send early warnings for the parameters like irregular bleeding, variations in pH levels and external pressure at wound site. In addition to the early warnings, this smart bandage concept can provide long term wound progression data to the health care providers. The smart bandage comprises a disposable part which has the inkjet printed sensors and a reusable part constituting the wireless electronics. This work is an important step towards futuristic wearable sensors for remote health care applications. PMID- 27353202 TI - Attachments. PMID- 27353199 TI - Efficacy of histotripsy combined with rt-PA in vitro. AB - Histotripsy, a form of therapeutic ultrasound that uses the mechanical action of microbubble clouds for tissue ablation, is under development to treat chronic deep vein thrombosis (DVT). We hypothesize that combining thrombolytic agents with histotripsy will enhance clot lysis. Recombinant tissue plasminogen activator (rt-PA) and rt-PA-loaded echogenic liposomes that entrain octafluoropropane microbubbles (OFP t-ELIP) were used in combination with highly shocked histotripsy pulses. Fully retracted porcine venous clots, with similar features of DVT occlusions, were exposed either to histotripsy pulses alone (peak negative pressures of 7-20 MPa), histotripsy and OFP t-ELIP, or histotripsy and rt-PA. Microbubble cloud activity was monitored with passive cavitation imaging during histotripsy exposure. The power levels of cavitation emissions from within the clot were not statistically different between treatment types, likely due to the near instantaneous rupture and destruction of OFP t-ELIP. The thrombolytic efficacy was significantly improved in the presence of rt-PA. These results suggest the combination of histotripsy and rt-PA could serve as a potent therapeutic strategy for the treatment of DVT. PMID- 27353205 TI - The Age of Love. PMID- 27353206 TI - Platinum-catalyzed cycloisomerizations of a common enyne: a divergent entry to cyclopropane sesquiterpenoids. Formal synthesis of sarcandralactone A. AB - A common enyne scaffold, resembling the structures of natural elemanes was found to be an excellent substrate for highly regioselective cycloisomerizations to produce diverse cyclopropane sesquiterpenoids. Platinum-catalysis was utilized to produce either lindenane or myliol cores, found in natural products, starting from enyne acetate 10 and its corresponding allene 12 respectively. Based on this concept, a second generation strategy allows the formal synthesis of sarcandralactone A. PMID- 27353207 TI - Neuroprotective Effects of Engineered Polymeric Nasal Microspheres Containing Hydroxypropyl-beta-cyclodextrin on beta-Amyloid (1-42)-Induced Toxicity. AB - beta-Amyloid (Abeta) plaques are the key neurotoxic assemblies in Alzheimer disease. It has been suggested that an interaction occurs between membrane cholesterol and Abeta aggregation in the brain. Cyclodextrins can remove cholesterol from cell membranes and change receptor function. This study aimed to investigate the effect of hydroxypropyl-beta-cyclodextrin (HP-CD) polymeric microspheres, based on chitosan or sodium alginate, on the levels of lipid peroxidation, reactive oxygen species production, and mitochondrial function in brain synaptosomes. The effect of microspheres on DNA fragmentation, the expression of Bcl-2, Bax, and Apex1 mRNAs in rat hippocampus after Abeta(1-42) peptide-induced neurotoxicity was also evaluated. Comparison with HP-CD raw material was performed. Abeta(1-42) treatment significantly decreased the mitochondrial activity of Apex1 and Bcl-2 mRNAs, induced DNA fragmentation, and increased mRNA levels of Bax. Treatment with HP-CD microspheres against Abeta(1 42) significantly reduced DNA fragmentation and increased the Bcl-2/Bax mRNA ratio and mitochondrial function. In addition, HP-CD microspheres used against Abeta(1-42) decreased the levels of lipid peroxidation and reactive oxygen species production. These results indicate that nasally administered spray-dried HP-CD microspheres are able to provide protection against Abeta(1-42)-induced neurotoxicity, due to the suppressed levels of oxidative stress and apoptotic signals in the rat hippocampus. PMID- 27353208 TI - Interpolymer Complexation Between Polyox and Carbopol, and Its Effect on Drug Release From Matrix Tablets. AB - Interaction between Polyox N12K and Carbopol 907 was pH dependent. A hydrogen bond-induced complexation began between pH 5.0 and 6.0 in an aqueous medium, and the interpolymer complex started to precipitate when the pH fell to 4.0. This complex was amorphous with a glass transition temperature of 3.17 degrees C. The molar ratio between ethylene oxide and acrylic acid units in the complex was 1.3:1. About 46% of the COOH groups in Carbopol 907 were H bonded to ether oxygen in Polyox. Theophylline release from tablets containing both polymers was a function of dissolution media pH, due to the pH-dependent interactions. In 0.01 N HCl, an insoluble tablet matrix formed in situ. 93% drug was released over 27 h via Fickian diffusion. In acetate buffer pH 4.0, the insoluble tablet matrix formed in situ disintegrated into tiny gel particles. Gel erosion controlled drug release at pH 4.0. These 2 polymers were unable to complex in a phosphate buffer pH 6.8. Therefore, the tablet matrix dissolved, and drug release followed the anomalous transport mechanism at pH 6.8. The release profiles in an acetate buffer pH 4.0 and phosphate buffer pH 6.8 were statistically same, and a sustained release over 12 h was achieved. PMID- 27353209 TI - Study on the Unfrozen Water Quantity of Maximally Freeze-Concentrated Solutions for Multicomponent Lyoprotectants. AB - The concentration of maximally freeze-concentrated solutions [Formula: see text] and the corresponding glass transition temperature [Formula: see text] and ante melting temperature [Formula: see text] of lyoprotectant solutions, are critical parameters for developing lyophilization process. Usually, the lyoprotectant solutions are multicomponent solutions composed of electrolytes, sugars, proteins, polymers, and other chemicals. In this article, the Wg' values of several multicomponent solutions including trehalose/NaCl, bovine serum albumin/NaCl, and hydroxyethyl starch/NaCl with water were determined by differential scanning calorimetry. A linear relationship between the unfrozen water fraction Wun and the initial solute concentrations Wi was found: Wun = ?(ai.Wi), which suggested that in the multicomponent solutions each solute could hydrate a certain amount of water ai (g water/g solute) that could not be frozen. The hypothesis was compared with more literature data. For the same solute in different solutions, variation in the fitted coefficient ai is noticed and discussed. If a "universal" value ai for each solute is adopted, both [Formula: see text] and [Formula: see text] for a multicomponent solution could be predicted if Couchman-Karasz equation is adopted for calculating glass transition temperature at the same time. The prediction discrepancies for [Formula: see text] with experimental data were less than 2 degrees C. The finding is discussed about its molecular basis and applicability. PMID- 27353210 TI - Integration of oral health-related quality of life instruments. AB - OBJECTIVES: To integrate items from two widely used oral health-related quality of life (OHRQoL) questionnaires, the General Oral Health Assessment Index (GOHAI) and the Oral Impacts on Daily Performances (OIDP), as well as culturally-specific items of the Oral Health Impact Profile (OHIP) into a four-dimensional OHRQoL model consisting of Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact. METHODS: Subjects came from an ancillary study of the Dimensions of Oral Health-Related Quality of Life Project (N=267 patients, mean age+/-SD: 54.0+/-17.2years, 58% women.) Patients filled in the original 49 items of OHIP and 22 additional OHRQoL items in a cross-sectional study. These additional items consisted of 7 culturally specific OHIP items and 15 GOHAI or OIDP items with unique content not covered in OHIP-49. Before data collection, three experts hypothesized to which of the four OHRQoL dimensions these items belong. Hypotheses were tested in correlation analyses between the 22 items and the four dimension scores that were derived from OHIP-49. RESULTS: Five of the 22 items did not provide sufficient information to which dimension they belong. In 16 of the remaining 17 items, the pattern of correlation coefficients fitted experts' a priori hypotheses. Acceptance of 16 of the 17 hypotheses was interpreted as evidence that additional (not in OHIP-49 contained) OHRQoL items can be assigned to Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact. CONCLUSION: Items of three OHRQoL instruments can be integrated into a dimensional OHRQoL model consisting of Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact. CLINICAL SIGNIFICANCE: Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact can serve as a simple and clinically appealing set of oral health-related quality of life (OHRQoL) dimensions and therefore provide an opportunity for simpler, but psychometrically improved OHRQoL measurement in the future. PMID- 27353212 TI - Enhancing the effectiveness of biological control programs of invasive species through a more comprehensive pest management approach. AB - Invasive species are one of the greatest economic and ecological threats to agriculture and natural areas in the US and the world. Among the available management tools, biological control provides one of the most economical and long term effective strategies for managing widespread and damaging invasive species populations of nearly all taxa. However, integrating biological control programs in a more complete integrated pest management approach that utilizes increased information and communication, post-release monitoring, adaptive management practices, long-term stewardship strategies, and new and innovative ecological and genetic technologies can greatly improve the effectiveness of biological control. In addition, expanding partnerships among relevant national, regional, and local agencies, as well as academic scientists and land managers, offers far greater opportunities for long-term success in the suppression of established invasive species. In this paper we direct our recommendations to federal agencies that oversee, fund, conduct research, and develop classical biological control programs for invasive species. By incorporating these recommendations into adaptive management strategies, private and public land managers will have far greater opportunities for long-term success in suppression of established invasive species. (c) 2016 Society of Chemical Industry. PMID- 27353211 TI - A Comparison of the Quality of Life of Patients With an Entirely Subcutaneous Implantable Defibrillator System Versus a Transvenous System (from the EFFORTLESS S-ICD Quality of Life Substudy). AB - The first clinical results from the Evaluation of Factors Impacting Clinical Outcome and Cost Effectiveness of the subcutaneous implantable cardioverter defibrillator (EFFORTLESS S-ICD) Registry on the entirely S-ICD system are promising, but the impact of the S-ICD system on patients' quality of life (QoL) is not known. We evaluated the QoL of patients with an S-ICD against an unrelated cohort with a transvenous (TV)-ICD system during 6 months of follow-up. Consecutively implanted patients with an S-ICD system were matched with patients with a TV-ICD system on a priori selected variables including baseline QoL. QoL was measured with the Short-Form Health Survey at baseline, 3, and 6 months after implant and compared using multivariable modeling with repeated measures. Patients with an S-ICD (n = 167) versus a TV-ICD system (n = 167) did not differ significantly on physical (p = 0.8157) and mental QoL scores (p = 0.9080) across baseline, 3, and 6 months after implantation in adjusted analyses. The evolution in physical (p = 0.0503) and mental scores (p = 0.3772) during follow-up was similar for both cohorts, as indicated by the nonsignificant interaction effect for ICD system by time. Both patients with an S-ICD system and a TV-ICD system experienced significant improvements in physical and mental QoL between time of implant and 3 months (both p's <0.0001) and between time of implant and 6 months (both p's <0.0001) but not between 3 and 6 months (both p's >0.05). In conclusion, these first results show that the QoL of patients with an S-ICD versus TV-ICD system is similar and that patients with either system experience improvements in QoL on the short term. PMID- 27353213 TI - Adherence to prophylactic treatment in patients with haemophilia in Germany. AB - INTRODUCTION: Adherence to prophylactic treatment in haemophilia is important for patient outcome. AIM: This study analysed the influence of potential impact factors on adherence assessed through the application of the German translation of the VERITAS-Pro questionnaire. METHODS: All members of the German haemophilia patient organisation (DHG) who suffer from severe or moderate haemophilia and are on continuous prophylactic treatment were asked to complete the VERITAS-Pro questionnaire. Further questions were added regarding the patients' age, severity of haemophilia, type A or B, frequency of prophylaxis, pain level, factor application self or non-self and co-morbidities. RESULTS: Responses of 397 patients on continuous prophylactic treatment, 0-80 years old, were analysed according to several age groups: 0-14, 15-19, 20-59 (20-29 and 30-39) and >=60 years of age. The mean total VERITAS-Pro score for the whole sample was 36.7 +/- 11.7 (range of 24-86). The scores were significantly higher, indicating the poorest adherence, in patients between 20 and 59 years of age (41.1 +/- 11.7) compared with the other age groups (30.0-35.7). Adherence to treatment was highest in patients between 0 and 14 years of age in all subscales of the VERITAS Pro. The following potential risk factors for non-adherence were evaluated in all age groups: organisation suffering (care by a haemophilia centre), severity and type of haemophilia, factor concentrate administration and the presence of co morbidities. CONCLUSION: The identification of significant differences between age groups in special subscales of adherence and impact factors offers tailored starting points for improvements of adherence to prophylactic treatment. PMID- 27353214 TI - Emerging peptide science from Japan. PMID- 27353215 TI - Balancing scientific accuracy and participant burden: testing the impact of sampling intensity on diurnal cortisol indices. AB - Despite the increasing popularity of incorporating salivary cortisol measurement into health and social science research, relatively little empirical work has been conducted on the number of saliva samples across the day required to capture key features of the diurnal cortisol rhythm, such as the diurnal cortisol slope, the area under the curve (AUC), and the cortisol awakening response (CAR). The primary purpose of this study is to compare slope, AUC, and CAR measures obtained from an intensive sampling protocol with estimates from less intensive protocols, to identify sampling protocols with minimal participant burden that still provide reasonably accurate assessment of each of these measures. Twenty-four healthy adults provided samples four times in the first hour awake, and then every hour throughout the rest of the day until bedtime (M = 17.8 samples/day; SD = 2.0), over two consecutive days (N = 862 total samples). We compared measures calculated from this maximum intensity protocol to measures calculated from two to six sampling points per day. Overall, results show that salivary cortisol protocols with two fixed samples (waking and bedtime) and three additional daily samples, closely approximates the full cortisol decline (slope). Abbreviated sampling protocols of total cortisol exposure across the day (AUC), however, were not well approximated by reduced sampling protocols. CAR measures based on only two samples, including waking cortisol and a second sample measured at a fixed time point between 30 and 60 min after waking, provided a measure of the CAR that closely approximated CAR measures obtained from 3 or 4 sampling points. PMID- 27353216 TI - Intraoperative and postoperative risk factors for anastomotic leakage and pneumonia after esophagectomy for cancer. AB - Morbidity and mortality after esophagectomy are often related to anastomotic leakage or pneumonia. This study aimed to assess the relationship of intraoperative and postoperative vital parameters with anastomotic leakage and pneumonia after esophagectomy. Consecutive patients who underwent transthoracic esophagectomy with cervical anastomosis for esophageal cancer from January 2012 to December 2013 were analyzed. Univariable and multivariable logistic regression analyses were used to determine potential associations of hemodynamic and respiratory parameters with anastomotic leakage or pneumonia. From a total of 82 included patients, 19 (23%) developed anastomotic leakage and 31 (38%) experienced pneumonia. The single independent factor associated with an increased risk of anastomotic leakage in multivariable analysis included a lower minimum intraoperative pH (OR 0.85, 95% CI 0.77-0.94). An increased risk of pneumonia was associated with a lower mean arterial pressure (MAP) in the first 12 hours after surgery (OR 0.93, 95% CI 0.86-0.99) and a higher maximum intraoperative pH (OR 1.14, 95% CI 1.02-1.27). Interestingly, no differences were noted for the MAP and inotrope requirement between patients with and without anastomotic leakage. A lower minimum intraoperative pH (below 7.25) is associated with an increased risk of anastomotic leakage after esophagectomy, whereas a lower postoperative average MAP (below 83 mmHg) and a higher intraoperative pH (above 7.34) increase the risk of postoperative pneumonia. These parameters indicate the importance of setting strict perioperative goals to be protected intensively. PMID- 27353217 TI - Ethanol extract of Lithospermum erythrorhizon Sieb. et Zucc. promotes osteoblastogenesis through the regulation of Runx2 and Osterix. AB - Bone remodeling and homeostasis are largely the result of the coordinated action of osteoblasts and osteoclasts. Osteoblasts are responsible for bone formation. The differentiation of osteoblasts is regulated by the transcription factors, Runx2 and Osterix. Natural products of plant origin are still a major part of traditional medicinal systems in Korea. The root of Lithospermum erythrorhizon Sieb. et Zucc. (LR), the purple gromwell, is an herbal medicine used for inflammatory and infectious diseases. LR is an anti-inflammatory and exerts anticancer effects by inducing the apoptosis of cancer cells. However, the precise molecular signaling mechanisms of osteoblastogenesis as regards LR and osteoblast transcription are not yet known. In this study, we investigated the effects of ethanol (EtOH) extract of LR (LES) on the osteoblast differentiation of C2C12 myoblasts induced by bone morphogenetic protein 4 (BMP4) and the potential involvement of Runx2 and Osterix in these effects. We found that the LES exhibited an ability to induce osteoblast differentiation. LES increased the expression of the osteoblast marker, alkaline phosphatase (ALP), as well as its activity, as shown by ALP staining and ALP activity assay. LES also increased mineralization, as shown by Alizarin Red S staining. Treatment with LES increased the protein levels (as shown by immunoblotting), as well as the transcriptional activity of Runx2 and Osterix and enhanced osteogenic activity. These results suggest that LES modulates osteoblast differentiation at least in part through Runx2 and Osterix. PMID- 27353218 TI - Adaptation of Campylobacter jejuni to biocides used in the food industry affects biofilm structure, adhesion strength, and cross-resistance to clinical antimicrobial compounds. AB - The emergence of biocide-adapted Campylobacter jejuni strains that developed into biofilms and their potential to develop clinical resistance to antimicrobial compounds was studied. C. jejuni was grown in sub-lethal concentrations of five biocides used in the food industry. C. jejuni exhibited adaptation to these biocides with increased minimum inhibitory concentrations. The 3-D structures of the biofilms produced by the biocide-adapted cells were investigated by atomic force microscopy (AFM). The results revealed marked variability in biofilm architecture, including ice-crystal-like structures. Adaptation to the biocides enhanced biofilm formation, with significant increases in biovolume, surface coverage, roughness, and the surface adhesion force of the biofilms. Adaptation to commercial biocides induced resistance to kanamycin and streptomycin. This study suggests that the inappropriate use of biocides may lead to cells being exposed to them at sub-lethal concentrations, which can result in adaptation of the pathogens to the biocides and a subsequent risk to public health. PMID- 27353219 TI - High-responsivity graphene-on-silicon slot waveguide photodetectors. AB - We demonstrated strong optical absorption in a graphene integrated silicon slot waveguide. Due to the increase in light intensity and decrease of optical mode confinement in the silicon slot, the graphene experienced an increased interaction to the in-plane light. A waveguide absorption of 0.935 dB MUm(-1) was measured at 1.55 MUm wavelengths. Based on the graphene-on-silicon slot waveguide, a compact and high-responsivity photodetector was demonstrated. Benefited from the lack of efficient electron cooling in the suspended graphene and the intensity enhancement effect in the nano slot, a maximum responsivity of 0.273 A W(-1) was achieved in the telecommunication band. PMID- 27353220 TI - Harm reduction-a systematic review on effects of alcohol reduction on physical and mental symptoms. AB - Based on the knowledge that alcohol misuse causes a multitude of diseases and increased mortality, this systematic review examines whether a reduction of the individual alcohol consumption can contribute to a minimization of health risks within a harm reduction approach. In fact, the reviewed 63 studies indicate that interventions aiming at alcohol reduction (including total abstinence as one possible therapeutic aim) indeed resulted in or were associated with positive effects in harmful, hazardous or alcohol-dependent drinkers. Major benefits were observed for reducing alcohol-associated injuries, recovery of ventricular heart function in alcoholic cardiomyopathy, blood pressure lowering, normalization of biochemical parameter, body weight reduction, histological improvement in pre cirrhotic alcohol-related liver disease and slowed progression of an already existing alcohol-attributable liver fibrosis. Furthermore, reduced withdrawal symptoms, prevalence of psychiatric episodes and duration of in-patient hospital days, improvement of anxiety and depression symptoms, self-confidence, physical and mental quality of life, fewer alcohol-related adverse consequences as well as lower psychosocial stress levels and better social functioning can result from reduced alcohol intake. The reviewed literature demonstrated remarkable socioeconomic cost benefits in areas such as the medical health-care system or workforce productivity. Individuals with heightened vulnerability further benefit significantly from alcohol reduction (e.g. hypertension, hepatitis C, psychiatric co-morbidities, pregnancy, but also among adolescents and young adults). Concluding, the reviewed studies strongly support and emphasize the importance and benefits of early initial screening for problematic alcohol use followed by brief and other interventions in first contact medical health-care facilities to reduce alcohol intake. PMID- 27353221 TI - Electrocatalytic monitoring of peptidic proton-wires. AB - The transfer of protons or proton donor/acceptor abilities is an important phenomenon in many biomolecular systems. One example is the recently proposed peptidic proton-wires (H-wires), but the ability of these His-containing peptides to transfer protons has only been studied at the theoretical level so far. Here, for the first time the proton transfer ability of peptidic H-wires is examined experimentally in an adsorbed state using an approach based on a label-free electrocatalytic reaction. The experimental findings are complemented by theoretical calculations at the ab initio level in a vacuum and in an implicit solvent. Experimental and theoretical results indicated Ala3(His-Ala2)6 to be a high proton-affinity peptidic H-wire model. The methodology presented here could be used for the further investigation of the proton-exchange chemistry of other biologically or technologically important macromolecules. PMID- 27353223 TI - The relationship between perifoveal achromatic, L- and M-cone acuity and retinal structure as assessed with multimodal high resolution imaging. AB - The relationships between perifoveal measures of achromatic-, L- and M-cone acuity and retinal structure were investigated in healthy young males. Thirty-two males, aged 20-39years, with normal foveal logMAR letter acuity and no observed ocular abnormalities participated in the study. Achromatic and isolated L- and M cone spatial acuity was measured in the dominant eye with a Sloan E letter of 90% achromatic decrement contrast or 23% increment cone contrast, respectively. Separately, the central part of the same eye was imaged with high-resolution spectral-domain optical coherence tomography (SD-OCT) and adaptive optics ophthalmoscopy (AOO). Thickness measures and cone density in the fovea and parafoveal region were not correlated with perifoveal structural measures. A significant correlation was observed between thicker retinal pigment epithelium (RPE) complex, higher cone density and better L-cone logMAR at 5deg eccentricity, but not for achromatic or M-cone logMAR. The results imply that single letter perifoveal L-cone acuity, rather than achromatic acuity, may provide a useful measure for assessing the structure-function relationship and detecting early changes in the perifoveal cone mosaic. PMID- 27353222 TI - Adolescents with irritable bowel syndrome report increased eating-associated symptoms, changes in dietary composition, and altered eating behaviors: a pilot comparison study to healthy adolescents. AB - BACKGROUND: About half of adult irritable bowel syndrome (IBS) patients report symptoms with eating and disordered eating habits. However, little is known about eating in adolescent IBS patients, a common age at which eating disorders develop. The aim of the study was to investigate if adolescents with IBS are more likely than healthy controls (HCs) to experience eating-associated symptoms (EAS), report disordered eating patterns, and show differences in diet composition. METHODS: A total of 99 adolescents between 15 and 21 years-of-age participated (n = 48 IBS; n = 51 HCs). All subjects completed three 24-h dietary recalls and questionnaires on EAS and disordered eating. KEY RESULTS: IBS patients were more likely to report EASs than HC (91.7% vs 28%, p < 0.001). Eating-associated symptoms were controlled by avoiding the offending food (97.7%), not eating any food even when hungry (43.2%), or vomiting after eating (13.6%). Compared to HC, IBS patients reported reduced daily intake of overall calories (1828 vs 2139; p < 0.05), fat (65.4 g vs 81.4 g, p < 0.05), and lactose (8.2 g vs 12.8 g, p < 0.01). No differences were found between IBS and HC in screening for disordered eating patterns or BMI, though IBS patients endorsed using potentially unhealthy eating behaviors in an attempt to control symptoms. CONCLUSIONS & INFERENCES: Eating-associated symptoms are very common in adolescents with IBS and associated with changes in eating behaviors and dietary composition. They do not appear to change BMI and risk for eating disorders. More research is needed to guide adolescents with IBS in making appropriate dietary changes to control EASs. PMID- 27353224 TI - An overview of quantitative approaches in Gestalt perception. AB - Gestalt psychology is often criticized as lacking quantitative measurements and precise mathematical models. While this is true of the early Gestalt school, today there are many quantitative approaches in Gestalt perception and the special issue of Vision Research "Quantitative Approaches in Gestalt Perception" showcases the current state-of-the-art. In this article we give an overview of these current approaches. For example, ideal observer models are one of the standard quantitative tools in vision research and there is a clear trend to try and apply this tool to Gestalt perception and thereby integrate Gestalt perception into mainstream vision research. More generally, Bayesian models, long popular in other areas of vision research, are increasingly being employed to model perceptual grouping as well. Thus, although experimental and theoretical approaches to Gestalt perception remain quite diverse, we are hopeful that these quantitative trends will pave the way for a unified theory. PMID- 27353226 TI - Use of Swedish smokeless tobacco (snus) and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA). AB - AIMS: It has been suggested that moist snuff (snus), a smokeless tobacco product that is high in nicotine and widespread in Scandinavia, increases the risk of Type 2 diabetes. Previous studies are however few, contradictory and, with regard to autoimmune diabetes, lacking. Our aim was to study the association between snus use and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA). METHOD: Analyses were based on incident cases (Type 2 diabetes, n = 724; LADA, n = 200) and population-based controls (n = 699) from a Swedish case-control study. Additional analyses were performed on cross-sectional data from the Norwegian HUNT study (n = 21 473) with 829 prevalent cases of Type 2 diabetes. Odds ratios (OR) were estimated adjusted for age, BMI family history of diabetes and smoking. Only men were included. RESULTS: No association between snus use and Type 2 diabetes or LADA was seen in the Swedish data. For Type 2 diabetes, the OR for > 10 box-years was 1.00 [95% confidence interval (CI), 0.47 to 2.11] and for LADA 1.01 (95% CI, 0.45 to 2.29). Similarly, in HUNT, the OR for Type 2 diabetes in ever-users was estimated at 0.91 (95% CI, 0.75 to 1.10) and in heavy users at 0.92 (95% CI, 0.46 to 1.83). CONCLUSION: The risk of Type 2 diabetes and LADA is unrelated to the use of snus, despite its high nicotine content. This opens the possibility of the increased risk of Type 2 diabetes seen in smokers may not be attributed to nicotine, but to other substances in tobacco smoke. PMID- 27353225 TI - The organization of the cone photoreceptor mosaic measured in the living human retina. AB - The cone photoreceptors represent the initial fundamental sampling step in the acquisition of visual information. While recent advances in adaptive optics have provided increasingly precise estimates of the packing density and spacing of the cone photoreceptors in the living human retina, little is known about the local cone geometric arrangement beyond a tendency towards hexagonal packing. We analyzed the cone mosaic in data from 10 normal subjects. A technique was applied to calculate the local average cone mosaic structure which allowed us to determine the hexagonality, spacing and orientation of local regions. Using cone spacing estimates, we find the expected decrease in cone density with retinal eccentricity and higher densities along the horizontal as opposed to the vertical meridians. Orientation analysis reveals an asymmetry in the local cone spacing of the hexagonal packing, with cones having a larger local spacing along the horizontal direction. This horizontal/vertical asymmetry is altered at eccentricities larger than 2 degrees in the superior meridian and 2.5 degrees in the inferior meridian. Analysis of hexagon orientations in the central 1.4 degrees of the retina shows a tendency for orientation to be locally coherent, with orientation patches consisting of between 35 and 240 cones. PMID- 27353227 TI - A scoping review of bereavement service outcomes. AB - OBJECTIVE: This scoping literature review, through finding and assessing researched bereavement service outcomes, sought to determine the state of bereavement services evaluation, to catalogue service types, and to identify which service or services, if any, demonstrate clear evidence of effectiveness. METHOD: Our methods included: (1) a literature search for published English language research articles from 2005-2015; (2) critical appraisal of articles to identify findings; (3) compilation of findings; and (4) determination of the relevance of our findings. RESULTS: Some 38 papers were found, and all were retained to identify the outcomes researched and research findings. Many different outcomes were studied in the 18 quantitative, 11 qualitative, and 9 mixed-methods investigations undertaken worldwide. Ten studies focused on level of grief, six on stress/distress level, six on grief knowledge, six on level of depression, and five on somatization or physical symptoms. Most commonly, a group of bereavement services was evaluated as a whole, followed by group therapy, individual counseling, written information, and other less common services. No group of services or individual service was determined to yield clear and convincing evidence of effectiveness. Regardless, all but one service were shown to have value-most often related to gaining grief information and/or emotional support. Until high-quality research studies have repeatedly revealed evidence of effectiveness, it is possible that the positive outcomes of bereavement services will be largely based on bereaved people receiving helpful educational information and emotional support from organizations and people prepared to help them. SIGNIFICANCE OF RESULTS: This project outlines existing bereavement service types and the state of science in relation to determination of outcomes. It offers suggestions to advance the state of science to validate or refine bereavement services. It brings to light the issue that bereavement service outcomes need to be carefully researched so that evidence can drive service refinement and expansion. It also highlights the importance of effective bereavement services. PMID- 27353228 TI - High-Loading Nickel Cobaltate Nanoparticles Anchored on Three-Dimensional N-Doped Graphene as an Efficient Bifunctional Catalyst for Lithium-Oxygen Batteries. AB - The lithium-oxygen batteries have been considered as the progressive energy storage equipment for their expected specific energy. To improve the electrochemical catalytic performance in the lithium-oxygen batteries, the NiCo2O4 nanoparticles (NCONPs) are firmly anchored onto the surface of the N doped reduced graphene oxide (N-rGO) by the hydrothermal method followed by low temperature calcination. Compared with the pure metallic oxide, the introduction of the rGO can create the high surface area, which give a good performance for ORR (oxygen reduction reaction), and improve the electrical conductivity between the NCONPs. The high-loading NCONPs also ensure the material to have great catalytic activity for OER (oxygen evolution reaction), and the rGO can be protected by the nanoparticles coating against the side reaction with the Li2O2. The as-synthesized NCO@N-rGO composites deliver a specific surface area (about 242.5 m(2) g(-1)), exhibiting three-dimensional (3D) porous structure, which provides a large passageway for the diffusion of the oxygen and benefits the infiltration of electrolyte and the storage of the discharge products. Owing to these special architectures features and intrinsic materials, the NCO@N-rGO cathode delivers a high specific capacity (6716 mAh g(-1)), great rate performance, and excellent cycling stability with cutoff capacity of 1000 mAh g( 1) (112 cycles) in the lithium-oxygen batteries. The improved electrochemical catalytic activity and the special 3D porous structure make the NCO@N-rGO composites be a promising candidate for Li-O2 batteries. PMID- 27353229 TI - Reversibility of developmental heat and cold plasticity is asymmetric and has long-lasting consequences for adult thermal tolerance. AB - The ability of insects to cope with stressful temperatures through adaptive plasticity has allowed them to thrive under a wide range of thermal conditions. Developmental plasticity is generally considered to be a non-reversible phenotypic change, e.g. in morphological traits, while adult acclimation responses are often considered to be reversible physiological responses. However, physiologically mediated thermal acclimation might not follow this general prediction. We investigated the magnitude and rate of reversibility of developmental thermal plasticity responses in heat and cold tolerance of adult flies, using a full factorial design with two developmental and two adult temperatures (15 and 25 degrees C). We show that cold tolerance attained during development is readily adjusted to the prevailing conditions during adult acclimation, with a symmetric rate of decrease or increase. In contrast, heat tolerance is only partly reversible during acclimation and is thus constrained by the temperature during development. The effect of adult acclimation on heat tolerance was asymmetrical, with a general loss of heat tolerance with age. Surprisingly, the decline in adult heat tolerance at 25 degrees C was decelerated in flies developed at low temperatures. This result was supported by correlated responses in two senescence-associated traits and in accordance with a lower rate of ageing after low temperature development, suggesting that physiological age is not reset at eclosion. The results have profound ecological consequences for populations, as optimal developmental temperatures will be dependent on the thermal conditions faced in the adult stage and the age at which they occur. PMID- 27353230 TI - Determining position, velocity and acceleration of free-ranging animals with a low-cost unmanned aerial system. AB - Unmanned aerial systems (UASs), frequently referred to as 'drones', have become more common and affordable and are a promising tool for collecting data on free ranging wild animals. We used a Phantom-2 UAS equipped with a gimbal-mounted camera to estimate position, velocity and acceleration of a subject on the ground moving through a grid of GPS surveyed ground control points (area ~1200 m(2)). We validated the accuracy of the system against a dual frequency survey grade GPS system attached to the subject. When compared with GPS survey data, the estimations of position, velocity and acceleration had a root mean square error of 0.13 m, 0.11 m s(-1) and 2.31 m s(-2), respectively. The system can be used to collect locomotion and localisation data on multiple free-ranging animals simultaneously. It does not require specialist skills to operate, is easily transported to field locations, and is rapidly and easily deployed. It is therefore a useful addition to the range of methods available for field data collection on free-ranging animal locomotion. PMID- 27353231 TI - Evolution and Engineering of Precisely Controlled Ge Nanostructures on Scalable Array of Ordered Si Nano-pillars. AB - The scalable array of ordered nano-pillars with precisely controllable quantum nanostructures (QNs) are ideal candidates for the exploration of the fundamental features of cavity quantum electrodynamics. It also has a great potential in the applications of innovative nano-optoelectronic devices for the future quantum communication and integrated photon circuits. Here, we present a synthesis of such hybrid system in combination of the nanosphere lithography and the self assembly during heteroepitaxy. The precise positioning and controllable evolution of self-assembled Ge QNs, including quantum dot necklace(QDN), QD molecule(QDM) and quantum ring(QR), on Si nano-pillars are readily achieved. Considering the strain relaxation and the non-uniform Ge growth due to the thickness-dependent and anisotropic surface diffusion of adatoms on the pillars, the comprehensive scenario of the Ge growth on Si pillars is discovered. It clarifies the inherent mechanism underlying the controllable growth of the QNs on the pillar. Moreover, it inspires a deliberate two-step growth procedure to engineer the controllable QNs on the pillar. Our results pave a promising avenue to the achievement of desired nano-pillar-QNs system that facilitates the strong light-matter interaction due to both spectra and spatial coupling between the QNs and the cavity modes of a single pillar and the periodic pillars. PMID- 27353232 TI - Update on medical treatment of small intestinal neuroendocrine tumors. AB - INTRODUCTION: Small intestinal (SI) neuroendocrine tumors (NETs) are relatively rare tumors. Due to the lack of symptom or specific symptoms, SI-NETs are often diagnosed at an advanced stage, making therapy challenging. The management of patients with advanced stage SI-NETS requires a multidisciplinary approach that combines surgical and medical treatment including novel targeted molecular therapies. AREAS COVERED: This article summarizes current strategies for the medical treatment of SI-NETS. Expert commentary: The treatment plan of advanced stage SI-NETs should be tailored in a case-by-case manner with the adoption of a multidisciplinary approach that combines different treatment options, including biological targeted therapies. In particular, we believe that the identification of the optimal treatment sequence(s), correct treatment timing and the selection of patients eligible to different treatments need specific investigation in controlled clinical trials. PMID- 27353233 TI - Modular modelling with Physiome standards. AB - KEY POINTS: The complexity of computational models is increasing, supported by research in modelling tools and frameworks. But relatively little thought has gone into design principles for complex models. We propose a set of design principles for complex model construction with the Physiome standard modelling protocol CellML. By following the principles, models are generated that are extensible and are themselves suitable for reuse in larger models of increasing complexity. We illustrate these principles with examples including an architectural prototype linking, for the first time, electrophysiology, thermodynamically compliant metabolism, signal transduction, gene regulation and synthetic biology. The design principles complement other Physiome research projects, facilitating the application of virtual experiment protocols and model analysis techniques to assist the modelling community in creating libraries of composable, characterised and simulatable quantitative descriptions of physiology. ABSTRACT: The ability to produce and customise complex computational models has great potential to have a positive impact on human health. As the field develops towards whole-cell models and linking such models in multi-scale frameworks to encompass tissue, organ, or organism levels, reuse of previous modelling efforts will become increasingly necessary. Any modelling group wishing to reuse existing computational models as modules for their own work faces many challenges in the context of construction, storage, retrieval, documentation and analysis of such modules. Physiome standards, frameworks and tools seek to address several of these challenges, especially for models expressed in the modular protocol CellML. Aside from providing a general ability to produce modules, there has been relatively little research work on architectural principles of CellML models that will enable reuse at larger scales. To complement and support the existing tools and frameworks, we develop a set of principles to address this consideration. The principles are illustrated with examples that couple electrophysiology, signalling, metabolism, gene regulation and synthetic biology, together forming an architectural prototype for whole-cell modelling (including human intervention) in CellML. Such models illustrate how testable units of quantitative biophysical simulation can be constructed. Finally, future relationships between modular models so constructed and Physiome frameworks and tools are discussed, with particular reference to how such frameworks and tools can in turn be extended to complement and gain more benefit from the results of applying the principles. PMID- 27353234 TI - Geographically weighted regression as a generalized Wombling to detect barriers to gene flow. AB - Barriers to gene flow play an important role in structuring populations, especially in human-modified landscapes, and several methods have been proposed to detect such barriers. However, most applications of these methods require a relative large number of individuals or populations distributed in space, connected by vertices from Delaunay or Gabriel networks. Here we show, using both simulated and empirical data, a new application of geographically weighted regression (GWR) to detect such barriers, modeling the genetic variation as a "local" linear function of geographic coordinates (latitude and longitude). In the GWR, standard regression statistics, such as R(2) and slopes, are estimated for each sampling unit and thus are mapped. Peaks in these local statistics are then expected close to the barriers if genetic discontinuities exist, capturing a higher rate of population differentiation among neighboring populations. Isolation-by-Distance simulations on a longitudinally warped lattice revealed that higher local slopes from GWR coincide with the barrier detected with Monmonier algorithm. Even with a relatively small effect of the barrier, the power of local GWR in detecting the east-west barriers was higher than 95 %. We also analyzed empirical data of genetic differentiation among tree populations of Dipteryx alata and Eugenia dysenterica Brazilian Cerrado. GWR was applied to the principal coordinate of the pairwise FST matrix based on microsatellite loci. In both simulated and empirical data, the GWR results were consistent with discontinuities detected by Monmonier algorithm, as well as with previous explanations for the spatial patterns of genetic differentiation for the two species. Our analyses reveal how this new application of GWR can viewed as a generalized Wombling in a continuous space and be a useful approach to detect barriers and discontinuities to gene flow. PMID- 27353235 TI - Convergent Synthesis of Novel Muramyl Dipeptide Analogues: Inhibition of Porphyromonas gingivalis-Induced Pro-inflammatory Effects by High Doses of Muramyl Dipeptide. AB - Porphyromonas gingivalis (P.g.)-induced TNF-alpha can be affected by muramyl dipeptide (MDP) in a biphasic concentration-dependent manner. We found that in P.g.-exposed macrophages, treatment with 10 MUg/mL of MDP (MDP-low) up-regulated TNF-alpha by 29%, while 100 MUg/mL or higher (MDP-high) significantly decreased it (16% to 38%). MDP-high was found to affect the ubiquitin-editing enzyme A20 and activator protein 1 (AP1). An AP1 binding site was found in the promoter region of A20. A20 promoter activity was up-regulated after transfection of AP1 cDNA in cells. Four analogues of MDP (3-6) were prepared through a convergent strategy involving the synthesis of two unique carbohydrate fragments, 7a and 7b, using the peptide coupling reagents, EDCI and HOAt. Analogue 4 improved MDP function and P.g.-induced activities. We propose a new signaling pathway for TNF alpha induction activated after exposing macrophages to both P.g. and MDP-high or analogue 4. PMID- 27353236 TI - The influence of gold(i) on the mechanism of thiolate, disulfide exchange. AB - The mechanism of gold(i)-thiolate, disulfide exchange was investigated by using initial-rate kinetic studies, 2D ((1)H-(1)H) ROESY NMR spectroscopy, and electrochemical/chemical techniques. The rate law for exchange is overall second order, first order in gold(i)-thiolate and disulfide. 2D NMR experiments show evidence of association between gold(i)-thiolate and disulfide. Electrochemical/chemical investigations do not show evidence of free thiolate and are consistent with a mechanism involving formation of a [Au-S, S-S], four centered metallacycle intermediate during gold(i)-thiolate, disulfide exchange. PMID- 27353237 TI - Acute effects of unilateral temporary stellate ganglion block on human atrial electrophysiological properties and atrial fibrillation inducibility. AB - BACKGROUND: In experimental models, stellate ganglion block (SGB) reduces the induction of atrial fibrillation (AF), while data in humans are limited. OBJECTIVE: The aim of this study was to assess the effect of unilateral SGB on atrial electrophysiological properties and AF induction in patients with paroxysmal AF. METHODS: Thirty-six patients with paroxysmal AF were randomized in a 2:1 order to temporary, transcutaneous, pharmaceutical SGB with lidocaine or placebo before pulmonary vein isolation. Lidocaine was 1:1 randomly infused to the right or left ganglion. Before and after randomization, atrial effective refractory period (ERP) of each atrium, difference between right and left atrial ERP, intra- and interatrial conduction time, AF inducibility, and AF duration were assessed. RESULTS: After SGB, right atrial ERP was prolonged from a median (1st-3rd quartile) of 240 (220-268) ms to 260 (240-300) ms (P < .01) and left atrial ERP from 235 (220-260) ms to 245 (240-280) ms (P < .01). AF was induced by atrial pacing in all 24 patients before SGB, but only in 13 patients (54%) after the intervention (P < .01). AF duration was shorter after SGB: 1.5 (0.0-5.8) minutes from 5.5 (3.0-12.0) minutes (P < .01). Intra- and interatrial conduction time was not significantly prolonged. No significant differences were observed between right and left SGB. No changes were observed in the placebo group. CONCLUSION: Unilateral temporary SGB prolonged atrial ERP, reduced AF inducibility, and decreased AF duration. An equivalent effect of right and left SGB on both atria was observed. These findings may have a clinical implication in the prevention of drug refractory and postsurgery AF and deserve further clinical investigation. PMID- 27353238 TI - Timely detection of superior vena cava laceration with thoracoscopy during lead extraction. PMID- 27353239 TI - Super-oscillatory focusing of circularly polarized light by ultra-long focal length planar lens based on binary amplitude-phase modulation. AB - In traditional optics, the focal spot size of a conventional lens is restricted to the diffraction limit 0.5lambda/NA, where lambda is the wavelength in vacuum and NA is the numerical aperture of the lens. Recently, various sub-diffraction focusing optical devices have been demonstrated, but they usually have short focal length and high numerical aperture. Moreover, they always suffer the problem of huge sidelobes near the focal spot and small field of view, especially when the focal spot size is less than the super-oscillation criteria 0.38lambda/NA. To address the problem, here, we reported a far-field sub diffraction point-focusing lens based on binary phase and amplitude modulation with ultra-long focal length 252.8 MUm (399.5lambda) and small numerical aperture 0.78, and experimentally demonstrated a super-oscillatory focusing of circularly polarized light with spot size 287 nm (0.454lambda), smaller than the diffraction limit 0.64lambda and the super-oscillation criterion 0.487lambda. What's more, on the focal plane, in the measured area within the radius of 142lambda, the largest sidelobe intensity is less than 26% of the central lobe intensity. Such ultra long distance super-oscillatory focusing with small sidelobes and large field of view has great potential applications in far-field super-resolution microscopy, ultra-high-density optical storage and nano-fabrication. PMID- 27353240 TI - Possible association of diazotrophs with marine zooplankton in the Pacific Ocean. AB - Dinitrogen fixation, the biological reduction in N2 gas to ammonia contributes to the supply of new nitrogen in the surface ocean. To understand the diversity and abundance of potentially diazotrophic (N2 fixing) microorganisms associated with marine zooplankton, especially copepods, the nifH gene was studied using zooplankton samples collected in the Pacific Ocean. In total, 257 nifH sequences were recovered from 23 nifH-positive DNA extracts out of 90 copepod samples. The nifH genes derived from cyanobacteria related to Trichodesmium, alpha- and gamma subdivisions of proteobacteria, and anaerobic euryarchaeota related to Methanosaeta concilii were detected. Our results indicated that Pleuromamma, Pontella, and Euchaeta were the major copepod genera hosting dinitrogen fixers, though we found no species-specific association between copepods and dinitrogen fixers. Also, the digital PCR provided novel data on the number of copies of the nifH gene in individual copepods, which we report the range from 30 to 1666 copies per copepod. This study is the first systematic study of zooplankton associated diazotrophs, covering a large area of the open ocean, which provide a clue to further study of a possible new hotspot of N2 fixation. PMID- 27353241 TI - Design and conduct of early phase drug studies in children: challenges and opportunities. AB - It has historically been very difficult to conduct early phase drug studies in children for a number of reasons related to ethics, acceptability, rarity, standardization, end points, safety, dosing and feasibility. Over the past decade there have been a number of developments including novel clinical trial design, in silico pharmacology and microdosing that have significantly enhanced the ability of investigators to conduct early phase drug studies in children. While the evolution of drug therapy is creating a series of new challenges, there has never been a better time for conducting drug studies in children. PMID- 27353242 TI - Demosaiced pixel super-resolution for multiplexed holographic color imaging. AB - To synthesize a holographic color image, one can sequentially take three holograms at different wavelengths, e.g., at red (R), green (G) and blue (B) parts of the spectrum, and digitally merge them. To speed up the imaging process by a factor of three, a Bayer color sensor-chip can also be used to demultiplex three wavelengths that simultaneously illuminate the sample and digitally retrieve individual set of holograms using the known transmission spectra of the Bayer color filters. However, because the pixels of different channels (R, G, B) on a Bayer color sensor are not at the same physical location, conventional demosaicing techniques generate color artifacts in holographic imaging using simultaneous multi-wavelength illumination. Here we demonstrate that pixel super resolution can be merged into the color de-multiplexing process to significantly suppress the artifacts in wavelength-multiplexed holographic color imaging. This new approach, termed Demosaiced Pixel Super-Resolution (D-PSR), generates color images that are similar in performance to sequential illumination at three wavelengths, and therefore improves the speed of holographic color imaging by 3 fold. D-PSR method is broadly applicable to holographic microscopy applications, where high-resolution imaging and multi-wavelength illumination are desired. PMID- 27353243 TI - Serious Adverse Events Reports: Analysis and Outcome of Review by an Institutional Ethics Committee of a Tertiary Care Hospital in Mumbai, India. AB - The Indian regulations for clinical trials were amended in January 2013 regarding reporting time lines, relatedness, and compensation for Serious Adverse Events (SAEs). Our study assessed the extent of regulatory compliance in reporting SAEs to the Institutional Ethics Committee (IEC) over 4 years (January 2009-January 2013) before and 18 months after (February 2013-July 2014) the amended regulations. SAE reports were studied retrospectively for reporting time lines, relatedness, compensation, and IEC response before and after the law revision. Before 2013 had 89/160 (55.6%) SAEs reports submitted late while in the after period, only 2/11 reports were delayed (18%). In the before period, 26 SAE reports mentioned "relatedness" of which only 15 (57.6%) stated about compensation. After 2013, all the 9 non-death reports were complete. The IEC took median 17 days to respond before 2013, while after 2013 responded within 5 days. Thus, there was poor compliance in terms of SAE reporting time lines before the revision of the law. PMID- 27353244 TI - Health Promotion Board-Ministry of Health Clinical Practice Guidelines: Obesity. AB - The Health Promotion Board (HPB) has developed the Clinical Practice Guidelines (CPG) on Obesity to provide health professionals in Singapore with recommendations for evidence-based interventions for obesity. This article summarises the introduction, epidemiology and executive summary of the key recommendations from the HPB-MOH CPG on Obesity for the information of SMJ readers. The chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Health Promotion Board website: http://www.hpb.gov.sg/cpg-obesity. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines. PMID- 27353245 TI - The efficacy and safety of extended-release methylphenidate following traumatic brain injury: a randomised controlled pilot study. AB - OBJECTIVE: To investigate the feasibility, safety and efficacy of extended release methylphenidate in enhancing processing speed, complex attentional functioning and everyday attentional behaviour after traumatic brain injury. DESIGN: Seven week randomised, placebo-controlled, double-blind, parallel pilot study. SETTING: Inpatient and outpatient Acquired Brain Injury Rehabilitation Program. PARTICIPANTS: Eleven individuals with reduced processing speed and/or attention deficits following complicated mild to severe traumatic brain injury. INTERVENTIONS: Participants were allocated using a blocked randomisation schedule to receive daily extended-release methylphenidate (Ritalin(r) LA at a dose of 0.6 mg/kg) or placebo (lactose) in identical capsules. MAIN OUTCOMES: Tests of processing speed and complex attention, and ratings of everyday attentional behaviour were completed at baseline, week 7 (on-drug), week 8 (off-drug) and 9 months follow-up. Vital signs and side effects were monitored from baseline to week 8. RESULTS: Three percent ( n = 11) of individuals screened participated (mean post-traumatic amnesia duration = 63.80 days, SD = 45.15). Results were analysed for six and four individuals on methylphenidate and placebo, respectively. Groups did not differ on attentional test performance or relative/therapist ratings of everyday attentional behaviour. One methylphenidate participant withdrew due to difficulty sleeping. Methylphenidate was associated with trends towards increased blood pressure and reported anxiety. CONCLUSION: Methylphenidate was not associated with enhanced processing speed, attentional functioning or everyday attentional behaviour after traumatic brain injury. Alternative treatments for attention deficits after traumatic brain injury should be explored given the limited feasibility of methylphenidate in this population. PMID- 27353246 TI - Combined exercise is more effective than aerobic exercise in the improvement of fall risk factors: a randomized controlled trial in community-dwelling older men. AB - OBJECTIVE: To compare the long-term effects of two community-based exercise programs on fall risk factors, such as balance, postural control, mobility and leg strength, in community-dwelling older men. DESIGN: Single-blinded randomized controlled trial, comparing three groups, with follow-ups at eight, 16, 24 and 32 weeks. SETTING: Older men independent-living residing in Maia city, Portugal. PARTICIPANTS: A total of 66 older men (aged 69.0 +/-4.9 years) were randomly assigned to an aerobic exercise group ( n = 22), a combined aerobic and resistance exercise group ( n = 22) or a control group ( n = 22). INTERVENTIONS: Both community-based exercise programs consisted of three sessions each week for 32 consecutive weeks and were planned for moderate-to-vigorous intensity. The control group had no exercise intervention. MEASUREMENTS: Main outcomes were measured by the Timed Up and Go Test, functional reach test, 30-second chair stand test and 6-minute walk test, on five different occasions. RESULTS: Repeated measures of analysis of covariance revealed significant main effects between time * group interaction in all outcomes over time (Timed Up and Go Test: p < 0.001; functional reach test: p = 0.002; 30-second chair stand: p = 0.001; 6-minute walk test: p < 0.001). Both exercise groups reported improvements; however, better performance was identified in the combined aerobic and resistance exercise group compared with the aerobic exercise group (-20.3% vs. -9.1% on the Timed Up and Go Test, +27.5% vs. +10.9% on the functional reach test, +20.8% vs. +7.3% on 30 second chair stand, +10.9% vs. +3.5% on 6-minute walk test). CONCLUSIONS: Adding resistance exercise to aerobic exercise improves factors associated with an increased risk of falls. However, both exercise regimes, combined or aerobic alone, are more effective than no exercise in the reduction of fall risk factors. ClinicalTrials.org #NCT01874132. PMID- 27353247 TI - The effectiveness of supplementary arm and upper body exercises following total hip arthroplasty for osteoarthritis in the elderly: a randomized controlled trial. AB - OBJECTIVE: To determine whether arm and upper body exercises in addition to the standard rehabilitation programme improve outcomes after hip arthroplasty. DESIGN: Prospective, parallel, randomized, controlled trial. SETTING: Orthopaedic and rehabilitation departments. SUBJECTS: A total of 70 patients >60 years of age, who underwent hip replacement, out of 98 eligible candidates after exclusion criteria were implemented. INTERVENTIONS: The study group took part in the supplementary arm and upper body exercise programme to be compared with the standard rehabilitation programme group. MAIN OUTCOME: The primary outcome was a Harris Hip Score. Secondary outcomes were: Hand grip strength and Medical Outcomes Study 36-Item Short-Form Health Survey. Outcomes were assessed preoperatively, two weeks after surgery and at 12 weeks follow-up. RESULTS: In the intervention group, significant improvements were found: in functional ability - Harris Hip Score after two (mean difference = 4.7 points) and 12 (mean difference = 5.85 points) weeks; in muscle strength - handgrip for both hands (mean difference for dominant hand = 4.16 and for the other hand = 2.8) after 12 weeks; and in role-physical dimension SF-36 Health Survey (mean difference = 6.42 points) after 12 weeks. CONCLUSION: Results of this study indicate that arm and upper body exercises in addition to the standard rehabilitation programme improve outcomes 12 weeks after hip arthroplasty. PMID- 27353248 TI - Online nutrition information for pregnant women: a content analysis. AB - Pregnant women actively seek health information online, including nutrition and food-related topics. However, the accuracy and readability of this information have not been evaluated. The aim of this study was to describe and evaluate pregnancy-related food and nutrition information available online. Four search engines were used to search for pregnancy-related nutrition web pages. Content analysis of web pages was performed. Web pages were assessed against the 2013 Australian Dietary Guidelines to assess accuracy. Flesch-Kincaid (F-K), Simple Measure of Gobbledygook (SMOG), Gunning Fog Index (FOG) and Flesch reading ease (FRE) formulas were used to assess readability. Data was analysed descriptively. Spearman's correlation was used to assess the relationship between web page characteristics. Kruskal-Wallis test was used to check for differences among readability and other web page characteristics. A total of 693 web pages were included. Web page types included commercial (n = 340), not-for-profit (n = 113), blogs (n = 112), government (n = 89), personal (n = 36) and educational (n = 3). The accuracy of online nutrition information varied with 39.7% of web pages containing accurate information, 22.8% containing mixed information and 37.5% containing inaccurate information. The average reading grade of all pages analysed measured by F-K, SMOG and FOG was 11.8. The mean FRE was 51.6, a 'fairly difficult to read' score. Only 0.5% of web pages were written at or below grade 6 according to F-K, SMOG and FOG. The findings suggest that accuracy of pregnancy related nutrition information is a problem on the internet. Web page readability is generally difficult and means that the information may not be accessible to those who cannot read at a sophisticated level. (c) 2016 John Wiley & Sons Ltd. PMID- 27353249 TI - Liquid self-diffusion of H2O and DMF molecules in Co-MOF-74: molecular dynamics simulations and dielectric spectroscopy studies. AB - In this work we use molecular dynamics simulations to study the diffusion of N,N dimethylformamide (DMF) and H2O as a function of temperature within the well known metal-organic framework Co2(dobdc).[G] (G = 2DMF.1H2O), also known as Co MOF-74. The molecular dynamics simulations show that the diffusivity of guest molecules, which is almost negligible at low temperatures (T < 200 K), increases in the range of 200 < T (K) < 400 up to 3 and 4 orders of magnitude for DMF and H2O, respectively. This molecular diffusion can be easily detected by dielectric spectroscopy as it gives rise to extrinsic interfacial polarization effects that result in an apparent "colossal" dielectric constant at room temperature, epsilonr' ~ 42 000 (T = 300 K, nu = 10 Hz). Furthermore, the measured dielectric constant exhibits a thermal dependence similar to that of the diffusion coefficient, revealing the parallelism of the dielectric response and the molecular diffusion as a function of temperature. These results highlight: (a) the great utility of the fast and non-destructive dielectric and impedance spectroscopy techniques for the study and detection of the molecular transport of small polar molecules within porous metal-organic frameworks and related materials; (b) the peculiarity and uniqueness of MOF materials with "medium" size nanopores containing guest molecules as they are solid materials in which the guest molecules display a liquid state-like behaviour close to room temperature; and PMID- 27353250 TI - Intranasal Administration of Chitosan Against Influenza A (H7N9) Virus Infection in a Mouse Model. AB - Influenza virus evolves constantly in an unpredictable fashion, making it necessary to vaccinate people annually for effective prevention and control of influenza. In general, however, during the first wave of an influenza outbreak caused by a newly emerging virus strain, influenza morbidity and mortality have been observed to rise sharply due to the lack of a matching vaccine. This necessitates the exploration of novel intervention approaches, particularly those prophylactic or therapeutic agents that have a broad range of antiviral activities and are also proven to be non-toxic. Here, we reported that stimulation of the innate immune system by intranasal administration of chitosan as a single agent was sufficient to completely protect BALB/c mice from lethal infection by H7N9 virus, a newly emerged viral strain that is highly pathogenic to humans. Remarkably, animals could still be protected against lethal challenge by H7N9 (10*LD50), even ten days after the intranasal chitosan administration. The significantly enhanced infiltration of leukocytes in the bronchoalveolar lavage and elevated levels of proinflammatory cytokines in the bronchia/lung tissues revealed the potent activation of mucosal immune responses by intranasally delivered chitosan. We also observed that chitosan can protect mice from three other virus strains. The marked breadth and magnitude of protection against diverse viral strains makes chitosan an attractive candidate as a universal anti-influenza agent. PMID- 27353251 TI - NLRP6 function in inflammatory monocytes reduces susceptibility to chemically induced intestinal injury. AB - NLRP6 is a member of the Nod-like receptor family, whose members are involved in the recognition of microbes and/or tissue injury. NLRP6 was previously demonstrated to regulate the production of interleukin (IL)-18 and is important for protecting mice against chemically induced intestinal injury and colitis associated colon cancer. However, the cellular mechanisms by which NLRP6 reduces susceptibility to colonic inflammation remain unclear. Here, we determined that NLRP6 expression is specifically upregulated in Ly6Chi inflammatory monocytes that infiltrate into the colon during dextran sulfate sodium (DSS)-induced inflammation. Adoptive transfer of wild-type (WT) Ly6Chi inflammatory monocytes into Nlrp6-/- mice was sufficient to protect them from mortality, significantly reducing intestinal permeability and damage. NLRP6-deficient inflammatory monocytes were defective in tumor necrosis factor alpha (TNFalpha) production, which was important for reducing DSS-induced mortality and was dependent on autocrine IL-18 signaling by inflammatory monocytes. Our data reveal a previously unappreciated role for NLRP6 in inflammatory monocytes, which are recruited after DSS-induced intestinal injury to promote barrier function and limit bacteria driven inflammation. This study highlights the importance of early cytokine responses, particularly NLRP6-dependent and IL-18-dependent TNFalpha production, in preventing chronic dysregulated inflammation. PMID- 27353252 TI - An LGG-derived protein promotes IgA production through upregulation of APRIL expression in intestinal epithelial cells. AB - p40, a Lactobacillus rhamnosus GG (LGG)-derived protein, transactivates epidermal growth factor receptor (EGFR) in intestinal epithelial cells, leading to amelioration of intestinal injury and inflammation. To elucidate mechanisms by which p40 regulates mucosal immunity to prevent inflammation, this study aimed to determine the effects and mechanisms of p40 on regulation of a proliferation inducing ligand (APRIL) expression in intestinal epithelial cells for promoting immunoglobulin A (IgA) production. p40 upregulated April gene expression and protein production in mouse small intestine epithelial (MSIE) cells, which were inhibited by blocking EGFR expression and kinase activity. Enteroids from Egfrfl/fl, but not Egfrfl/fl-Vil-Cre mice with EGFR specifically deleted in intestinal epithelial cells, exhibited increased April gene expression by p40 treatment. p40-conditioned media from MSIE cells increased B-cell class switching to IgA+ cells and IgA production, which was suppressed by APRIL receptor neutralizing antibodies. Treatment of B cells with p40 did not show any effects on IgA production. p40 treatment increased April gene expression and protein production in small intestinal epithelial cells, fecal IgA levels, IgA+B220+, IgA+CD19+, and IgA+ plasma cells in lamina propria of Egfrfl/fl, but not of Egfrfl/fl-Vil-Cre, mice. Thus p40 upregulates EGFR-dependent APRIL production in intestinal epithelial cells, which may contribute to promoting IgA production. PMID- 27353253 TI - Responses of Poa annua and three bentgrass species (Agrostis spp.) to adult and larval feeding of annual bluegrass weevil, Listronotus maculicollis (Coleoptera: Curculionidae). AB - The annual bluegrass weevil (ABW), Listronotus maculicollis Kirby, is an economically important pest of short-cut turfgrass in Eastern North America. Wide spread insecticide resistance warrants the development of alternative management strategies for this pest. ABW damage typically occurs in areas with a high percentage of annual bluegrass, Poa annua L., the preferred ABW host. Damage to bentgrasses, Agrostis spp., is much rarer and usually less severe. To aid the implementation of host plant resistance as an alternative ABW management strategy we investigated the tolerance of three bentgrass species to ABW feeding. Responses of P. annua, creeping bentgrass, Agrostis stolonifera L., colonial bentgrass, Agrostis capillaris L., and velvet bentgrass, Agrostis canina L., to adult and larval feeding were compared in greenhouse experiments. Grass responses were measured as visual damage, dry weight of the grass stems and leaves, color, density and overall grass quality. To determine possible mechanisms of grass tolerance constitutive fiber and silicon content were also determined. The three bentgrass species tolerated 2-3 times higher numbers of ABW adults and larvae than P. annua before displaying any significant quality decrease. Creeping bentgrass had the lowest damage ratings. ABW infestation caused higher plant yield reduction in P. annua (up to 42%) than in bentgrasses. Observed differences among the grass species in fiber and silicon content in the plant tissue are unlikely to play a role in the resistance of bentgrasses to ABW. Our findings clearly show that A. stolonifera is the best grass species for the implementation of host plant resistance in ABW management. PMID- 27353254 TI - Anti-tumor effect of beta-glucan from Lentinus edodes and the underlying mechanism. AB - beta-Glucans are well known for its various bioactivities, but the underlying mechanism has not been fully understood. This study focuses on the anti-tumor effect and the potential mechanism of a branched beta-(1, 3)-glucan (LNT) extracted from Lentinus edodes. The in vivo data indicated that LNT showed a profound inhibition ratio of ~75% against S-180 tumor growth, even significantly higher than the positive control of Cytoxan (~54%). Interestingly, LNT sharply promoted immune cells accumulation into tumors accompanied by cell apoptosis and inhibition of cell proliferation during tumor development. Furthermore, LNT not only up-regulated expressions of the tumor suppressor p53, cell cycle arrestin p21 and pro-apoptotic proteins of Bax and caspase 3/9, but also down-regulated PARP1 and anti-apoptotic protein Bcl-2 expressions in tumor tissues. It was first found that LNT initiated p53-dependent signaling pathway to suppress cell proliferation in vitro, and the caspase-dependent pathway to induce cell apoptosis in vivo. The underlying anti-tumor mechanism was proposed that LNT activated immune responses to induce cell apoptosis through caspase 3-dependent signaling pathway and to inhibit cell proliferation possibly via p53-dependent signaling pathway in vivo. Besides, LNT inhibited angiogenesis by suppressing VEGF expression, leading to slow progression of tumors. PMID- 27353255 TI - Short Communication: HIV Controller T Cells Effectively Inhibit Viral Replication in Alveolar Macrophages. AB - Macrophages are targets of HIV-1 infection, and control of viral replication within these cells may be an important component of a T-cell-based vaccine. Although several studies have analyzed the ability of CD8+ T cells to inhibit viral replication in monocyte-derived macrophages, the effect of T cells on HIV-1 infected tissue macrophages is less clear. We demonstrate here that both CD4+ and CD8+ T-cell effectors from HIV controllers are capable of suppressing viral replication in bronchoalveolar lavage-derived alveolar macrophages. These findings have implications for HIV-1 vaccine and eradication strategies. PMID- 27353256 TI - Maintenance of B cells during chronic murine Trypanosoma brucei gambiense infection. AB - African trypanosomosis is a debilitating parasitic disease occurring in large parts of sub-Saharan Africa. Trypanosoma brucei gambiense accounts for 98% of the reported HAT infections and causes a chronic, gradually progressing disease. Multiple experimental murine models for trypanosomosis have demonstrated inflammation-dependent apoptosis of splenic follicular B (FoB) cells and the destruction of B-cell memory against previously encountered pathogens. Here, we report that during murine infection with a chronic T. b. gambiense field isolate, FoB cells are retained. This coincided with reduced levels of IFN-gamma and TNF alpha during the acute phase of the infection. This result suggests that in chronic infections with low virulent parasites, less inflammation is elicited and consequently no FoB cell destruction occurs. PMID- 27353258 TI - IGF-I/EGF and E2 signaling crosstalk through IGF-IR conduit point affects breast cancer cell adhesion. AB - Epidermal growth factor (EGF)/insulin like growth factor-I (IGF-I) and Estradiol (E2) can regulate biological functions of hormone-dependent tumor cells. Fibronectin (FN) is a large glycoprotein abundantly expressed in breast cancer extracellular matrices (ECMs) postulated to be a marker of aggressiveness during cancer pathogenesis. In this study we demonstrate that IGF-I/EGF as well E2 strongly increase the adhesion of the MCF-7 breast cancer cells onto FN. Moreover, IGF-IR is necessary for the IGF-I-/EGF- and E2-induced cell adhesion. Erk1/2 inhibition abolished the IGF-I-/EGF-/E2-induced MCF-7 cell adhesion, suggesting that this regulation of cell adhesion is perpetrated through Erk1/2 downstream signaling. Erk1/2 signaling was shown to modulate IGF-IR status as its' inhibition attenuates both IGF-IR expression and activation. Notably, EGF and E2 enhanced the mRNA as well as protein expression of IGF-IR in MCF-7 cells. Confocal microscopy demonstrated that treatment of MCF-7 cells with IGF-I or EGF induced actin reorganization, which was attenuated with Erk1/2 inhibition. Interestingly, IGF-I treatment induced a co-localization of IGF-IR and FAK, which was evident mostly at the cell membranes of MCF-7 cells. In summary, IGF-IR was shown to be a convergence point for the IGF-/EGF- and E2-dependent MCF-7 cell adhesion onto FN. PMID- 27353259 TI - Training health professionals in shared decision making: Update of an international environmental scan. AB - OBJECTIVE: To update an environmental scan of training programs in SDM for health professionals. METHODS: We searched two systematic reviews for SDM training programs targeting health professionals produced from 2011 to 2015, and also in Google and social networks. With a standardized data extraction sheet, one reviewer extracted program characteristics. All completed extraction forms were validated by a second reviewer. RESULTS: We found 94 new eligible programs in four new countries and two new languages, for a total of 148 programs produced from 1996 to 2015-an increase of 174% in four years. The largest percentage appeared since 2012 (45.27%). Of the 94 newprograms, 42.55% targeted licensed health professionals (n=40), 8.51% targeted pre-licensure (n=8), 28.72% targeted both (n=27), 20.21% did not specify (n=19), and 5.32% targeted also patients (n=5). Only 23.40% of the new programs were reported as evaluated, and 21.28% had published evaluations. CONCLUSIONS: Production of SDM training programs is growing fast worldwide. Like the original scan, this update indicates that SDM training programs still vary widely. Most still focus on the single provider/patient dyad and few are evaluated. PRACTICE IMPLICATIONS: This update highlights the need to adapt training programs to interprofessional practice and to evaluate them. PMID- 27353260 TI - Enhancement of Combined Umami and Salty Taste by Glutathione in the Human Tongue and Brain. AB - Glutathione, a natural substance, acts on calcium receptors on the tongue and is known to enhance basic taste sensations. However, the effects of glutathione on brain activity associated with taste sensation on the tongue have not been determined under standardized taste delivery conditions. In this study, we investigated the sensory effect of glutathione on taste with no effect of the smell when glutathione added to a combined umami and salty taste stimulus. Twenty six volunteers (12 women and 14 men; age 19-27 years) performed a sensory evaluation of taste of a solution of monosodium L-glutamate and sodium chloride, with and without glutathione. The addition of glutathione changed taste qualities and significantly increased taste intensity ratings under standardized taste delivery conditions (P < 0.001). Functional magnetic resonance imaging showed that glutathione itself elicited significant activation in the left ventral insula. These results are the first to demonstrate the enhancing effect of glutathione as reflected by brain data while tasting an umami and salty mixture. PMID- 27353261 TI - Discontinuation and restarting in patients on statin treatment: prospective open cohort study using a primary care database. AB - OBJECTIVES: To estimate rates of discontinuation and restarting of statins, and to identify patient characteristics associated with either discontinuation or restarting. DESIGN: Prospective open cohort study. SETTING: 664 general practices contributing to the Clinical Practice Research Datalink in the United Kingdom. Data extracted in October 2014. PARTICIPANTS: Incident statin users aged 25-84 years identified between January 2002 and September 2013. Patients with statin prescriptions divided into two groups: primary prevention and secondary prevention (those already diagnosed with cardiovascular disease). Patients with statin prescriptions in the 12 months before study entry were excluded. MAIN OUTCOME MEASURES: Discontinuation of statin treatment (first 90 day gap after the estimated end date of a statin prescription), and restarting statin treatment for those who discontinued (defined as any subsequent prescription between discontinuation and study end). RESULTS: Of 431 023 patients prescribed statins as primary prevention with a median follow-up time of 137 weeks, 47% (n=204 622) discontinued treatment and 72% (n=147 305) of those who discontinued restarted. Of 139 314 patients prescribed statins as secondary prevention with median follow-up time of 182 weeks, 41% (n=57 791) discontinued treatment and 75% (43 211) of those who discontinued restarted. Younger patients (aged <=50 years), older patients (>=75 years), women, and patients with chronic liver disease were more likely to discontinue statins and less likely to restart. However, patients in ethnic minority groups, current smokers, and patients with type 1 diabetes were more likely to discontinue treatment but then were more likely to restart, whereas patients with hypertension and type 2 diabetes were less likely to discontinue treatment and more likely to restart if they did discontinue. These results were mainly consistent in the primary prevention and secondary prevention groups. CONCLUSIONS: Although a large proportion of statin users discontinue, many of them restart. For many patient groups previously considered as "stoppers," the problem of statin treatment "stopping" could be part of the wider issue of poor adherence. Identification of patient groups associated with completely stopping or stop-starting behaviour has positive implications for patients and doctors as well as suggesting areas for future research. PMID- 27353257 TI - A synopsis on aging-Theories, mechanisms and future prospects. AB - Answering the question as to why we age is tantamount to answering the question of what is life itself. There are countless theories as to why and how we age, but, until recently, the very definition of aging - senescence - was still uncertain. Here, we summarize the main views of the different models of senescence, with a special emphasis on the biochemical processes that accompany aging. Though inherently complex, aging is characterized by numerous changes that take place at different levels of the biological hierarchy. We therefore explore some of the most relevant changes that take place during aging and, finally, we overview the current status of emergent aging therapies and what the future holds for this field of research. From this multi-dimensional approach, it becomes clear that an integrative approach that couples aging research with systems biology, capable of providing novel insights into how and why we age, is necessary. PMID- 27353262 TI - HIV drug resistance levels in adults failing first-line antiretroviral therapy in an urban and a rural setting in South Africa. AB - OBJECTIVES: Urban and rural HIV treatment programmes face different challenges in the long-term management of patients. There are few studies comparing drug resistance profiles in patients accessing treatment through these programmes. The aim of this study was to perform such a comparison. METHODS: HIV drug resistance data and associated treatment and monitoring information for adult patients failing first-line therapy in an urban and a rural programme were collected. Data were curated and managed in SATuRN RegaDB before statistical analysis using Microsoft Excel 2013 and stata Ver14, in which clinical parameters, resistance profiles and predicted treatment responses were compared. RESULTS: Data for 595 patients were analysed: 492 patients from a rural setting and 103 patients from an urban setting. The urban group had lower CD4 counts at treatment initiation than the rural group (98 vs. 126 cells/MUL, respectively; P = 0.05), had more viral load measurements performed per year (median 3 vs. 1.4, respectively; P < 0.01) and were more likely to have no drug resistance mutations detected (35.9% vs. 11.2%, respectively; P < 0.01). Patients in the rural group were more likely to have been on first-line treatment for a longer period, to have failed for longer, and to have thymidine analogue mutations. Notwithstanding these differences, the two groups had comparable predicted responses to the standard second-line regimen, based on the genotypic susceptibility score. Mutations accumulated in a sigmoidal fashion over failure duration. CONCLUSIONS: The frequency and patterns of drug resistance, as well the intensity of virological monitoring, in adults with first-line therapy failure differed between the urban and rural sites. Despite these differences, based on the genotypic susceptibility scores, the majority of patients across the two sites would be expected to respond well to the standard second-line regimen. PMID- 27353263 TI - In Vitro Assessment of Combinations of Enterovirus Inhibitors against Enterovirus 71. AB - Enterovirus 71 (EV-A71) is a major causative pathogen of hand, foot, and mouth disease (HFMD) epidemics. No antiviral therapies are currently available for treating EV-A71 infections. Here, we selected five reported enterovirus inhibitors (suramin, itraconazole [ITZ], GW5074, rupintrivir, and favipiravir) with different mechanisms of action to test their abilities to inhibit EV-A71 replication alone and in combination. All selected compounds have anti-EV-A71 activities in cell culture. The combination of rupintrivir and ITZ or favipiravir was synergistic, while the combination of rupintrivir and suramin was additive. The combination of suramin and favipiravir exerted a strong synergistic antiviral effect. The observed synergy was not due to cytotoxicity, as there was no significant increase in cytotoxicity when compounds were used in combinations at the tested doses. To investigate the potential inhibitory mechanism of favipiravir against enterovirus, two favipiravir-resistant EV-A71 variants were independently selected, and both of them carried an S121N mutation in the finger subdomain of the 3D polymerase. Reverse engineering of this 3D S121N mutation into an infectious clone of EV-A71 confirmed the resistant phenotype. Moreover, viruses resistant to ITZ or favipiravir remained susceptible to other inhibitors. Most notably, combined with ITZ, rupintrivir prevented the development of ITZ resistant variants. Taken together, these results provide a rational basis for the design of combination regimens for use in the treatment of EV-A71 infections. PMID- 27353264 TI - Eravacycline Pharmacokinetics and Challenges in Defining Humanized Exposure In Vivo. AB - We assessed the pharmacokinetic profile of eravacycline, a novel antibiotic of the tetracycline class, and determined the dose in an immunocompetent murine thigh infection model that would provide free-drug exposure similar to that observed in humans after the administration of 1 mg/kg intravenously (i.v.) every 12 h (q12h). Eravacycline demonstrated a nonlinear protein-binding profile. The 2.5-mg/kg i.v. q12h dose in mice resulted in an area under the concentration-time curve for the free, unbound fraction of the drug of 1.64 mg . h/liter, which closely resembles the human exposure level. PMID- 27353265 TI - Antibacterial Efficacy of Eravacycline In Vivo against Gram-Positive and Gram Negative Organisms. AB - Members of the tetracycline class are frequently classified as bacteriostatic. However, recent findings have demonstrated an improved antibacterial killing profile, often achieving >=3 log10 bacterial count reduction, when such antibiotics have been given for periods longer than 24 h. We aimed to study this effect with eravacycline, a novel fluorocycline, given in an immunocompetent murine thigh infection model over 72 h against two methicillin-resistant Staphylococcus aureus (MRSA) isolates (eravacycline MICs = 0.03 and 0.25 MUg/ml) and three Enterobacteriaceae isolates (eravacycline MICs = 0.125 to 0.25 MUg/ml). A humanized eravacycline regimen, 2.5 mg/kg of body weight given intravenously (i.v.) every 12 h (q12h), demonstrated progressively enhanced activity over the 72-h study period. A cumulative dose response in which bacterial density was reduced by more than 3 log10 CFU at 72 h was noted over the study period in the two Gram-positive isolates, and eravacycline performed similarly to comparator antibiotics (tigecycline, linezolid, and vancomycin). A cumulative dose response with eravacycline and comparators (tigecycline and meropenem) over the study period was also observed in the Gram-negative isolates, although more variability in bacterial killing was observed for all antibacterial agents. Overall, a bacterial count reduction of >=3 log was achieved in one of the three isolates with both eravacycline and tigecycline, while meropenem achieved a similar endpoint against two of the three isolates. Bactericidal activity is typically defined in vitro over 24 h; however, extended regimen studies in vivo may demonstrate an improved correlation with clinical outcomes by better identification of antimicrobial effects. PMID- 27353266 TI - In Vitro and In Vivo Effectiveness of an Innovative Silver-Copper Nanoparticle Coating of Catheters To Prevent Methicillin-Resistant Staphylococcus aureus Infection. AB - In this study, silver/copper (Ag/Cu)-coated catheters were investigated for their efficacy in preventing methicillin-resistant Staphylococcus aureus (MRSA) infection in vitro and in vivo Ag and Cu were sputtered (67/33% atomic ratio) on polyurethane catheters by direct-current magnetron sputtering. In vitro, Ag/Cu coated and uncoated catheters were immersed in phosphate-buffered saline (PBS) or rat plasma and exposed to MRSA ATCC 43300 at 10(4) to 10(8) CFU/ml. In vivo, Ag/Cu-coated and uncoated catheters were placed in the jugular vein of rats. Directly after, MRSA (10(7) CFU/ml) was inoculated in the tail vein. Catheters were removed 48 h later and cultured. In vitro, Ag/Cu-coated catheters preincubated in PBS and exposed to 10(4) to 10(7) CFU/ml prevented the adherence of MRSA (0 to 12% colonization) compared to uncoated catheters (50 to 100% colonization; P < 0.005) and Ag/Cu-coated catheters retained their activity (0 to 20% colonization) when preincubated in rat plasma, whereas colonization of uncoated catheters increased (83 to 100%; P < 0.005). Ag/Cu-coating protection diminished with 10(8) CFU/ml in both PBS and plasma (50 to 100% colonization). In vivo, Ag/Cu-coated catheters reduced the incidence of catheter infection compared to uncoated catheters (57% versus 79%, respectively; P = 0.16) and bacteremia (31% versus 68%, respectively; P < 0.05). Scanning electron microscopy of explanted catheters suggests that the suboptimal activity of Ag/Cu catheters in vivo was due to the formation of a dense fibrin sheath over their surface. Ag/Cu coated catheters thus may be able to prevent MRSA infections. Their activity might be improved by limiting plasma protein adsorption on their surfaces. PMID- 27353267 TI - Analysis of the Endogenous Deoxynucleoside Triphosphate Pool in HIV-Positive and Negative Individuals Receiving Tenofovir-Emtricitabine. AB - Tenofovir (TFV) disoproxil fumarate (TDF) and emtricitabine (FTC), two nucleos(t)ide analogs (NA), are coformulated as an anti-HIV combination tablet for treatment and preexposure prophylaxis (PrEP). TDF/FTC may have effects on the deoxynucleoside triphosphate (dNTP) pool due to their similar structures and similar metabolic pathways. We carried out a comprehensive clinical study to characterize the effects of TDF/FTC on the endogenous dNTP pool, from baseline to 30 days of TDF/FTC therapy, in both treatment-naive HIV-positive and HIV-negative individuals. dATP, dCTP, dGTP, and TTP were quantified in peripheral blood mononuclear cells (PBMC) with a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology. Forty individuals (19 HIV-positive) were enrolled and underwent a baseline visit and then received TDF/FTC for at least 30 days. Longitudinal measurements were analyzed using mixed-model segmented linear regression analysis. The dNTPs were reduced by 14% to 37% relative to the baseline level within 3 days in both HIV-negative and HIV-positive individuals (P <= 0.003). These reductions persisted to various degrees at day 30. These findings indicate that dNTP pools are influenced by TDF/FTC therapy. This may alter cellular homeostasis and could increase the antiviral effect through a more favorable analog/dNTP ratio. Further work is needed to elucidate mechanisms, to evaluate the clinical significance of these findings, and to further probe differences between HIV-negative and HIV-positive individuals. (This study has been registered at ClinicalTrials.gov under identifier NCT01040091.). PMID- 27353269 TI - Population Pharmacokinetics of Tenofovir in HIV-1-Uninfected Members of Serodiscordant Couples and Effect of Dose Reporting Methods. AB - Antiretroviral preexposure prophylaxis (PrEP) with once-daily dosing of tenofovir and tenofovir-emtricitabine was shown to be effective for preventing HIV-1 infection in individuals who had HIV-1-seropositive partners (the Partners PrEP Study). We developed a population pharmacokinetic model for tenofovir and investigated the impacts of different dose reporting methods. Dosing information was collected as patient-reported dosing information (PRDI) from 404 subjects (corresponding to 1,280 drug concentration records) from the main trial and electronic monitoring-based adherence data collected from 211 subjects (corresponding to 327 drug concentration records) in an ancillary adherence study. Model development was conducted with NONMEM (7.2), using PRDI with a steady-state assumption or using PRDI replaced with electronic monitoring records where available. A two-compartment model with first-order absorption was the best model in both modeling approaches, with the need for an absorption lag time when electronic monitoring-based dosing records were included in the analysis. Age, body weight, and creatinine clearance were significant covariates on clearance, but only creatinine clearance was retained in the final models per stepwise selection. Sex was not a significant covariate on clearance. Tenofovir population pharmacokinetic parameter estimates and the precisions of the parameters from the two final models were comparable with the point estimates of the parameters, differing from 0% to 35%, and bootstrap confidence intervals widely overlapped. These findings indicate that PRDI was sufficient for population pharmacokinetic model development in this study, with a high level of adherence per multiple measures. PMID- 27353268 TI - Macrolones Are a Novel Class of Macrolide Antibiotics Active against Key Resistant Respiratory Pathogens In Vitro and In Vivo. AB - As we face an alarming increase in bacterial resistance to current antibacterial chemotherapeutics, expanding the available therapeutic arsenal in the fight against resistant bacterial pathogens causing respiratory tract infections is of high importance. The antibacterial potency of macrolones, a novel class of macrolide antibiotics, against key respiratory pathogens was evaluated in vitro and in vivo MIC values against Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, and Haemophilus influenzae strains sensitive to macrolide antibiotics and with defined macrolide resistance mechanisms were determined. The propensity of macrolones to induce the expression of inducible erm genes was tested by the triple-disk method and incubation in the presence of subinhibitory concentrations of compounds. In vivo efficacy was assessed in a murine model of S. pneumoniae-induced pneumonia, and pharmacokinetic (PK) profiles in mice were determined. The in vitro antibacterial profiles of macrolones were superior to those of marketed macrolide antibiotics, including the ketolide telithromycin, and the compounds did not induce the expression of inducible erm genes. They acted as typical protein synthesis inhibitors in an Escherichia coli transcription/translation assay. Macrolones were characterized by low to moderate systemic clearance, a large volume of distribution, a long half-life, and low oral bioavailability. They were highly efficacious in a murine model of pneumonia after intraperitoneal application even against an S. pneumoniae strain with constitutive resistance to macrolide-lincosamide-streptogramin B antibiotics. Macrolones are the class of macrolide antibiotics with an outstanding antibacterial profile and reasonable PK parameters resulting in good in vivo efficacy. PMID- 27353270 TI - Activities of Tedizolid and Linezolid Determined by the Reference Broth Microdilution Method against 3,032 Gram-Positive Bacterial Isolates Collected in Asia-Pacific, Eastern Europe, and Latin American Countries in 2014. AB - Tedizolid and linezolid in vitro activities against 3,032 Gram-positive pathogens collected in Asia-Pacific, Eastern European, and Latin American medical centers during 2014 were assessed. The isolates were tested for susceptibility by the current reference broth microdilution methods. Due to concern over the effect of MIC endpoint criteria on the results of testing the oxazolidinones tedizolid and linezolid, MIC endpoint values were read by two methods: (i) reading the MIC at the first well where the trailing began without regard for pinpoint trailing, according to CLSI M07-A10 and M100-S26 document instructions for reading linezolid (i.e., 80% inhibition of growth; these reads were designated tedizolid 80 and linezolid 80), and (ii) at 100% inhibition of growth (designated tedizolid 100 and linezolid 100). All Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group, and Enterococcus faecalis isolates were inhibited at tedizolid 80 and 100 MIC values of 0.25 and 0.5, 0.25 and 0.25, 0.25 and 0.5, 0.12 and 0.25, and 0.5 and 1 MUg/ml, respectively. Generally, MIC50 and MIC90 results for tedizolid 80 and linezolid 80 were one doubling dilution lower than those read at 100% inhibition. Tedizolid was 4- to 8-fold more potent than linezolid against all the isolates tested regardless of the MIC endpoint criterion used. Despite the differences in potency, >99.9% of isolates tested in this survey were susceptible to both linezolid and tedizolid using CLSI and EUCAST interpretive criteria. In conclusion, tedizolid demonstrated greater in vitro potency than linezolid against Gram-positive pathogens isolated from patients in medical centers across the Asia-Pacific region, Eastern Europe, and Latin America. PMID- 27353272 TI - Raised inflammatory markers may indicate poorer quality of life in advanced cancer. PMID- 27353271 TI - Clinical Resistance to Velpatasvir (GS-5816), a Novel Pan-Genotypic Inhibitor of the Hepatitis C Virus NS5A Protein. AB - Velpatasvir (VEL, GS-5816) is a novel pan-genotypic hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor with activity against genotype 1 (GT1) to GT6 HCV replicons. In a phase 1b 3-day monotherapy study, patients treated with a 150-mg dose of GS-5816 had a mean maximal HCV RNA decline of >=3.3 log10 IU/ml in GT1a, -1b, -2, -3, and -4. This report characterizes virologic resistance to VEL in these patients. NS5A resistance-associated substitutions (RASs) were detected by deep sequencing (1% cutoff) pretreatment in 22/70 patients, i.e., 10/35 (29%) patients with GT1a, 1/8 (13%) with GT1b, 4/8 (50.0%) with GT2, 5/17 (29.4%) with GT3, and 2/2 (100.0%) with GT4. In GT1a and GT3 patients, pretreatment RASs were associated with a slightly reduced HCV RNA response compared to that of patients without pretreatment RASs; among patients with GT1b, GT2, and GT4, no significant difference in response was observed in those with or without pretreatment RASs. Following treatment, the pattern of emergent RASs was more complex for GT1a than for the other genotypes. In GT1a, substitutions emerged at positions M28, Q30, L31, P32, H58, E92, and Y93, with the most prevalent substitutions at positions Y93, M28, and L31. RASs were observed at two positions in GT1b and GT2 (Y93 and L31), three positions in GT3 (Y93, L31, and E92), and four positions in GT4 (L28, M31, P32L, and Y93). RASs that were present pretreatment persisted through the 48-week follow-up period; however, RASs emerging during treatment were more likely to decline both in prevalence and in frequency within the viral population during follow-up. (This study has been registered at ClinicalTrials.gov under registration no. NCT01740791.). PMID- 27353273 TI - Non-beneficial treatments in hospital at the end of life: a systematic review on extent of the problem. AB - PURPOSE: To investigate the extent of objective 'non-beneficial treatments (NBTs)' (too much) anytime in the last 6 months of life in routine hospital care. DATA SOURCES: English language publications in Medline, EMBASE, PubMed, Cochrane library, and the grey literature (January 1995-April 2015). STUDY SELECTION: All study types assessing objective dimensions of non-beneficial medical or surgical diagnostic, therapeutic or non-palliative procedures administered to older adults at the end of life (EOL). DATA EXTRACTION: A 13-item quality score estimated independently by two authors. RESULTS OF DATA SYNTHESIS: Evidence from 38 studies indicates that on average 33-38% of patients near the EOL received NBTs. Mean prevalence of resuscitation attempts for advanced stage patients was 28% (range 11-90%). Mean death in intensive care unit (ICU) was 42% (range 11-90%); and mean death rate in a hospital ward was 44.5% (range 29-60%). Mean prevalence of active measures including dialysis, radiotherapy, transfusions and life support treatment to terminal patient was 7-77% (mean 30%). Non-beneficial administration of antibiotics, cardiovascular, digestive and endocrine treatments to dying patients occurred in 11-75% (mean 38%). Non-beneficial tests were performed on 33 50% of patients with do-not-resuscitate orders. From meta-analyses, the pooled prevalence of non-beneficial ICU admission was 10% (95% CI 0-33%); for chemotherapy in the last six weeks of life was 33% (95% CI 24-41%). CONCLUSION: This review has confirmed widespread use of NBTs at the EOL in acute hospitals. While a certain level of NBT is inevitable, its extent, variation and justification need further scrutiny. PMID- 27353275 TI - High levels of serum homocysteine in non-alcoholic steatohepatitis. PMID- 27353274 TI - Histopathological assessment of calcification and inflammation of calcific aortic valves from patients with and without diabetes mellitus. AB - BACKGROUND: Calcific aortic valve disease (CAVD) is the most common valvular heart disease and likely evolves from inflammatory pre-conditions in the valve. Type II diabetes mellitus (DMII) has been associated with pathogenesis of CAVD, however, the mechanism initiating CAVD in DMII is not well understood and the human valve pathology in DMII has not been described. We therefore performed quantitative histological analyses of aortic valves of CAVD patients with and without DMII. METHODS: CAVD human aortic valves (n=45) obtained after surgical valve replacement were examined macroscopically with gross measurements of calcified areas. Inflammation and calcification were assessed by immunohistochemistry and immunofluorescence staining. RESULTS: Calcification was increased in diabetic patients according to gross measurements (p<0.01) and alizarin red staining (p=0.05). Early calcification markers, including Runx2 (p=0.02) and alkaline phosphatase (ALP, p=0.03) were significantly elevated in diabetic patients. Furthermore, in diabetic patients we found significantly increased expression of annexin II (p=0.04) and annexin V (p=0.04), both of which are thought to play a role in microcalcification formation via apoptosis or extracellular vesicle release. Macrophage numbers were comparable in both groups (p=0.41), while the expression of the pro-inflammatory protein S100A9 (p<0.01) was significantly decreased in diabetic individuals. Evaluation of lymphocytes revealed similar CD8 (p=0.45) and CD4 (p=0.92) T cell counts in diabetic and non diabetic aortic valves. CONCLUSION: Aortic valves from diabetic patients show more calcification, while inflammation is similar in both patient populations. Considering the generally accepted theory of an inflammation-dependent mechanism of calcification, these data suggest that in patients with CAVD requiring valve replacement, diabetic patients could be molecularly in a more advanced disease stage with a higher grade of mineralization than non-diabetic patients. PMID- 27353276 TI - 'There will be blood'. Differences in the pictorial representation of the arterial spurt of blood in Caravaggio and followers. PMID- 27353277 TI - Obesity and hypomagnesemia. AB - BACKGROUND: Whether low serum magnesium is an epiphenomenon related with obesity or, whether obesity per se is cause of hypomagnesemia, remains to be clarified. OBJECTIVE: To examine the relationship between body weight status and hypomagnesemia in apparently healthy subjects. METHODS: A total of 681 healthy individuals aged 30 to 65years were enrolled in A cross-sectional study. Extreme exercise, chronic diarrhea, alcohol intake, use of diuretics, smoking, oral magnesium supplementation, diabetes, malnutrition, hypertension, liver disease, thyroid disorders, and renal damage were exclusion criteria. Based in the Body Mass Index (BMI), body weight status was defined as follows: normal weight (BMI <25kg/m2); overweight (BMI >=25<30 BMIkg/m2); and obesity (BMI >=30kg/m2). Hypomagnesemia was defined by serum magnesium concentration <=0.74mmol/L. A multiple logistic regression analysis was used to compute the odds ratio (OR) between body weight status (independent variables) and hypomagnesemia (dependent variable). RESULTS: The multivariate logistic regression analysis showed that dietary magnesium intake (OR 2.11; 95%CI 1.4-5.7) but no obesity (OR 1.53; 95%CI 0.9-2.5), overweight (OR 1.40; 95%CI 0.8-2.4), and normal weight (OR 0.78; 95%CI 0.6-2.09) were associated with hypomagnesemia. A subsequent logistic regression analysis adjusted by body mass index, waist circumference, total body fat, systolic and diastolic blood pressure, and triglycerides levels showed that hyperglycemia (2.19; 95%CI 1.1-7.0) and dietary magnesium intake (2.21; 95%CI 1.1 8.9) remained associated with hypomagnesemia. CONCLUSIONS: Our results show that body weight status is not associated with hypomagnesemia and that, irrespective of obesity, hyperglycemia is cause of hypomagnesemia in non-diabetic individuals. PMID- 27353278 TI - Factors contributing to the development of overt encephalopathy in liver cirrhosis patients. AB - The aim of this study was to clarify the relationships among psychometric testing results, blood ammonia (NH3) levels, electrolyte abnormalities, and degree of inflammation, and their associations with the development of overt hepatic encephalopathy (HE) in liver cirrhosis (LC) patients. The relationships between covert HE and blood NH3, sodium (Na), and C-reactive protein (CRP) were examined in 40 LC patients. The effects of elevated NH3, hyponatremia, and elevated CRP on the development of overt HE were also investigated. The covert HE group had significantly lower serum Na levels and significantly higher serum CRP levels. During the median observation period of 11 months, 10 patients developed overt HE, and the results of multivariate analysis showed that covert HE and elevated blood NH3 were factors contributing to the development of overt HE. Electrolyte abnormalities and mild inflammation are involved in the pathogenesis of HE. Abnormal psychometric testing results and hyperammonemia are linked to subsequent development of overt HE. PMID- 27353279 TI - Malaria in British military personnel deployed to Sierra Leone: a case series. AB - From December 2014 to April 2015, seven cases of malaria were seen in 1530 military personnel deployed to Sierra Leone on Operation GRITROCK in response to the West African Ebola outbreak, despite predeployment briefings, prescription of chemoprophylactic agents and bite prevention measures. The cases have prompted discussion regarding the efficacy of current measures and how to prevent future cases in deployed military personnel or more widely, those working in malaria risk environments. All of the cases have made a full recovery and returned to work. We discuss what can be learnt concerning the choice of chemoprophylactic agent and whether anything further be added to standard operating procedures regarding bite prevention and treatment of cases. PMID- 27353281 TI - A negatively charged transmembrane aspartate residue controls activation of the relaxin-3 receptor RXFP3. AB - Relaxin-3 is an insulin/relaxin superfamily neuropeptide involved in the regulation of food intake and stress response via activation of its cognate receptor RXFP3, an A-class G protein-coupled receptor (GPCR). In recent studies, a highly conserved ExxxD motif essential for binding of relaxin-3 has been identified at extracellular end of the second transmembrane domain (TMD2) of RXFP3. For most of the A-class GPCRs, a highly conserved negatively charged Asp residue (Asp(2.50) using Ballesteros-Weinstein numbering and Asp128 in human RXFP3) is present at the middle of TMD2. To elucidate function of the conserved transmembrane Asp128, in the present work we replaced it with other residues and the resultant RXFP3 mutants all retained quite high ligand-binding potency, but their activation and agonist-induced internalization were abolished or drastically decreased. Thus, the negatively charged transmembrane Asp128 controlled transduction of agonist-binding information from the extracellular region to the intracellular region through maintaining RXFP3 in a metastable state for efficient conformational change induced by binding of an agonist. PMID- 27353280 TI - BjMYB1, a transcription factor implicated in plant defence through activating BjCHI1 chitinase expression by binding to a W-box-like element. AB - We previously identified the W-box-like-4 (Wbl-4) element (GTAGTGACTCAT), one of six Wbl elements in the BjC-P promoter of the unusual chitinase gene BjCHI1 from Brassica juncea, as the core element responsive to fungal infection. Here, we report the isolation and characterization of the cognate transcription factor interacting with the Wbl-4 element. Using Wbl-4 as a target, we performed yeast one-hybrid screening of a B. juncea cDNA library and isolated an R2R3-MYB transcription factor designated as BjMYB1. BjMYB1 was localized in the nucleus of plant cells. EMSA assays confirmed that BjMYB1 binds to the Wbl-4 element. Transiently expressed BjMYB1 up-regulated the activity of the BjC-P promoter through its binding to the Wbl-4 element in tobacco (Nicotiana benthamiana) leaves. In B. juncea, BjMYB1 displayed a similar induced expression pattern as that of BjCHI1 upon infection by the fungus Botrytis cinerea Moreover, heterogeneous overexpression of BjMYB1 significantly elevated the resistance of transgenic Arabidopsis thaliana to the fungus B. cinerea These results suggest that BjMYB1 is potentially involved in host defence against fungal attack through activating the expression of BjCHI1 by binding to the Wbl-4 element in the BjC-P promoter. This finding demonstrates a novel DNA target of plant MYB transcription factors. PMID- 27353282 TI - Ovarian cancer patients' and their family members' perspectives on novel vaccine and virotherapy trials. AB - BACKGROUND/AIMS: Some of the most promising avenues of cancer clinical investigation center on immunotherapeutic approaches. These approaches have provided notable gains in cancer therapeutics with recent Food and Drug Administration approvals of agents of this class in several types of cancers, although gains for ovarian cancer lag behind. This study examined perceptions of therapeutic trials including immunotherapy and virotherapy among ovarian cancer patients and their family members. METHODS: A total of 72 semi-structured qualitative interviews were conducted with 33 patients and 39 family members at two National Cancer Institute-designated comprehensive cancer centers. Eligible patients were diagnosed with epithelial ovarian, primary peritoneal, or fallopian tube carcinoma and had experience with clinical trial conversations; family members were nominated by patients and interviewed separately. Applied thematic analysis was used to understand and interpret the data. RESULTS: More participants were aware of vaccine trials than virus trials, although more than half had heard of at least one of them. Initial reactions to vaccine trials were generally favorable. For many, childhood experience with vaccines lent a familiar frame of reference. Virus trials elicited more negative initial reactions, including the use of adjectives such as "scary" and "dreadful." Viruses seemed contagious or difficult to control. Increased receptivity to these trials occurred in the context of limited therapeutic options and cancer recurrence. Most participants, including those not immediately drawn to these types of trials, indicated openness to learning more. CONCLUSION: Although vaccine and viral trials are both immunologically based therapeutic approaches, patients who are offered these trials may perceive their potential benefit and safety quite differently. There is a need to consider terminology, solicit and address "gut reactions," and provide information that enables patients and their family members to better understand the science behind these trials. PMID- 27353283 TI - Managing Troponin Testing. PMID- 27353284 TI - Discharge Glucose Is Not Associated With Short-Term Adverse Outcomes in Emergency Department Patients With Moderate to Severe Hyperglycemia. AB - STUDY OBJECTIVE: Hyperglycemia is frequently encountered in the emergency department (ED), and there is no consensus on optimal care before discharge. The importance of glucose reduction in the ED is unknown. We seek to determine whether an association exists between discharge glucose and 7-day adverse outcomes. METHODS: A cohort design with retrospective chart review was conducted at a high-volume urban ED. Patients were included if any glucose level was greater than or equal to 400 mg/dL and they were discharged from the ED. Generalized estimating equation models were created for the 7-day outcomes with a primary predictor of discharge glucose. RESULTS: The cohort consisted of 422 patients with 566 ED encounters. Mean arrival and discharge glucose were 491 mg/dL (SD 82 mg/dL) and 334 mg/dL (SD 101 mg/dL), respectively. In the 7-day follow-up period, 62 (13%) and 36 (7%) patients had a repeat ED visit for hyperglycemia and were hospitalized, respectively. Two patients had diabetic ketoacidosis. After adjustment for arrival glucose, whether a chemistry panel was obtained, amount of intravenous fluids administered, and amount of subcutaneous insulin administered, discharge glucose was not associated with repeat ED visit for hyperglycemia (adjusted odds ratio 0.997; 95% confidence interval 0.993 to 1.001) or hospitalization for any reason (adjusted odds ratio 0.998; 95% confidence interval 0.995 to 1.002). CONCLUSION: ED discharge glucose in patients with moderate to severe hyperglycemia was not associated with 7-day outcomes of repeat ED visit for hyperglycemia or hospitalization. Attaining a specific glucose goal before discharge in patients with hyperglycemia may be less important than traditionally thought. PMID- 27353285 TI - Prevalence of diabetes mellitus and impaired glucose metabolism in the adult population of the Basque Country, Spain. AB - AIMS: To assess the prevalence of diabetes mellitus and impaired glucose metabolism in the Basque Country and their relationship with cardiovascular risk factors. METHODS: A population-based, cross-sectional, cluster sampling design study was carried out in an adult (>=18 years) Basque population. A total of 847 participants completed a questionnaire on personal and family medical history and lifestyle. Anthropometric variables and blood pressure were measured and biochemical analysis and an oral glucose tolerance test (75 g) were also performed. RESULTS: The total prevalence of diabetes was 10.6% (95% CI 8.65 12.95). Among them 6.3% (95% CI 4.79-8.22) had previously been diagnosed and 4.3% (95% CI 3.04-5.92) were not aware that they had diabetes. Impaired glucose tolerance was present in 7.2% (95% CI 5.53-9.15) and impaired fasting glucose in 3.8% (95% CI 2.64-5.37) of the population. In total, 21.6% of the population had some type of glucose metabolism disturbance, with a higher rate among men (28.3 vs 16.3%; P<0.001) and with the rate increasing with age. Risk factors independently associated with the development of diabetes were: male sex [odds ratio 4.58 (95% CI 2.34-8.97)]; abdominal obesity [odds ratio 2.80 (95% CI 1.47 5.36)]; high triglyceride levels [odds ratio 2.46 (95% CI 1.26-4.81)]; hypertension [odds ratio 2.40 (95% CI 1.16-4.96)]; family history of diabetes [odds ratio 2.30 (95% CI 1.25-4.24)]; high LDL cholesterol levels [odds ratio 1.83 (95% CI 1.01-3.31)] and older age [odds ratio 1.08 (95% CI 1.05-1.10)]. CONCLUSIONS: The prevalence of diabetes in the Basque Country was lower than in Spain and was independently associated with family history of diabetes and with cardiovascular risk factors such as abdominal obesity, hypertension, high LDL cholesterol levels and high triglyceride levels, which were also observed in those with prediabetes. PMID- 27353286 TI - Characteristics of patients who made a return visit within 72 hours to the emergency department of a Singapore tertiary hospital. AB - INTRODUCTION: 72-hour emergency department (ED) reattendance is a widely-used quality indicator for quality of care and patient safety. It is generally assumed that patients who return within 72 hours of ED discharge (72-hour re-attendees) received inadequate treatment or evaluation. The current literature also suggests considerable variation in probable causes of 72-hour ED reattendances internationally. This study aimed to understand the characteristics of these patients at the ED of a Singapore tertiary hospital. METHODS: We conducted a retrospective cohort study on all ED visits between 1 January 2013 and 31 December 2013. 72-hour re-attendees were compared against non-re-attendees based on patient demographics, mode of arrival, patient acuity category status (i.e. P1/P2/P3/P4), seniority ranking of doctor-in-charge and medical diagnoses. Multivariate analysis using the generalised linear model was conducted on variables associated with 72-hour ED re-attendance. RESULTS: Among 104,751 unique patients, 3,065 (2.93%) were in the 72-hour re-attendees group. Multivariate analysis showed that the following risk factors were associated with higher risk of returning within 72 hours: male gender, older age, arrival by ambulance, triaged as P2, diagnoses of heart problems, abdominal pain or viral infection (all p < 0.001), and Chinese ethnicity (p = 0.006). There was no significant difference in the seniority ranking of the doctor-in-charge between both groups (p = 0.419). CONCLUSION: Several patient and event factors were associated with higher risk of being a 72-hour re-attendee. This study forms the basis for hypothesis generation and further studies to explore reasons behind reattendances so that interventions can be developed to target high-risk groups. PMID- 27353287 TI - Sevoflurane during CPR for intraoperative cardiac arrest: To discontinue or to maintain? PMID- 27353288 TI - Automated external defibrillation skills by naive schoolchildren. AB - AIM: Early defibrillation should achieve the highest survival rates when applied within the first minutes after the collapse. Public access defibrillation programs have increased the population awareness of the importance of defibrillation. Schoolchildren should be trained in basic life support (BLS) skills and some countries have included BLS in their school syllabus. However, little is known of the current knowledge and ability of schoolchildren to use an automated external defibrillator (AED). METHODS: A multicentric descriptive study, 1295 children from 6 to 16 years of age without previous BLS or AED training. Subjects performed a simulation with an AED and a manikin with no training or feedback and were evaluated by means of a checklist. RESULTS: A total of 258 participants (19.9%) were able to simulate an effective and safe defibrillation in less than 3min and 52 (20.1% of this group) performed it successfully. A significant correlation between objective and age group was observed (G=0.172) (p<0.001). The average time to deliver a shock was 83.3+/ 26.4s; that time decreased significantly with age [6 YO (108.3+/-40.4) vs. 16 YO (64.7+/-18.6)s] (p<0.001). CONCLUSIONS: Around 20% of schoolchildren without prior training are able to use an AED correctly in less than 3min following the device's acoustic and visual instructions. However, only one-fifth of those who showed success managed to complete the procedure satisfactorily. These facts should be considered in order to provide a more accurate definition and effective implementation of BLS/AED teaching and training at schools. PMID- 27353289 TI - Quantitative analysis of duty cycle in pediatric and adolescent in-hospital cardiac arrest. AB - AIMS: Quality cardiopulmonary resuscitation (CPR) is associated with improved outcomes during cardiac arrest. Duty cycle (DC) represents an understudied element of CPR quality. Our objective was to quantitatively analyze DC during actual pediatric and adolescent in-hospital cardiac arrest (IHCA). METHODS: Prospective observational study of IHCA at a large academic children's hospital. CPR variables included DC (%) up to the first 10min of recorded chest compressions (CCs). American Heart Association (AHA) DC compliance was prospectively defined as an average event DC of 50+/-5%. Percentage of events compliant with AHA DC was compared to a priori hypothesized compliance percentage of 25% using chi-square. Association between DC quartiles and categories of depth (<38, 38-49, >=50mm) and rate (<100, 100-120, >120min(-1)) were analyzed by chi square test for trend. RESULTS: Between October 2006 and June 2015, 97 events in 87 patients were analyzed. Mean DC for events was 40+/-2.8%. DC quartiles: Q1 (DC <=38.3%), Q2 (>38.3-40.1%), Q3 (>40.1-42.1%), Q4 (>42.1%). Only 5 (5.2%) events met AHA DC compliance, significantly less than the a priori hypothesis of 25% (p<0.001). Average CC rates trended higher across DC quartiles: (Q1) 105+/-9; (Q2) 106+/-9; (Q3) 112+/-8; and (Q4) 118+/-14min(-1); p<0.001. Other CPR quality variables were not associated with DC. There was no association between DC and survival. CONCLUSIONS: Compression DC during resuscitation of actual child and adolescent IHCA met AHA recommendations in only 5% of events. In this series we found no association of DC with CC depth or survival. PMID- 27353290 TI - Biomolecular environment, quantification, and intracellular interaction of multifunctional magnetic SERS nanoprobes. AB - Multifunctional composite nanoprobes consisting of iron oxide nanoparticles linked to silver and gold nanoparticles, Ag-Magnetite and Au-Magnetite, respectively, were introduced by endocytic uptake into cultured fibroblast cells. The cells containing the non-toxic nanoprobes were shown to be displaceable in an external magnetic field and can be manipulated in microfluidic channels. The distribution of the composite nanostructures that are contained in the endosomal system is discussed on the basis of surface-enhanced Raman scattering (SERS) mapping, quantitative laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) micromapping, and cryo soft X-ray tomography (cryo soft-XRT). Cryo soft-XRT of intact, vitrified cells reveals that the composite nanoprobes form intra-endosomal aggregates. The nanoprobes provide SERS signals from the biomolecular composition of their surface in the endosomal environment. The SERS data indicate the high stability of the nanoprobes and of their plasmonic properties in the harsh environment of endosomes and lysosomes. The spectra point at the molecular composition at the surface of the Ag-Magnetite and Au-Magnetite nanostructures that is very similar to that of other composite structures, but different from the composition of pure silver and gold SERS nanoprobes used for intracellular investigations. As shown by the LA-ICP-MS data, the uptake efficiency of the magnetite composites is approximately two to three times higher than that of the pure gold and silver nanoparticles. PMID- 27353291 TI - Strain gradient development in 3-dimensional extracellular matrix scaffolds during in vitro mechanical stimulation. AB - This study analyzed strain variations in 3D ECM scaffolds using a membrane adherent model (MM) and a direct elongation model (DM). Computational models were solved for target strains from 1 to 10% at varied scaffold thicknesses and intra scaffold slices. DM strain profiles were uniform within the scaffold and independent of thickness. However, a wide range of strains developed with substantial volume experiencing significantly off-target strain. MM strain profiles varied throughout the scaffold, exhibiting significantly reduced average strain with increasing thickness. These findings are important for tissue engineering studies since biological responses are commonly attributed to a single strain level that only partially describes the mechanical condition, making it difficult to develop precise causal relationships. Spatial strain variations and reduced average strain may warrant targeted sampling for cell response and should be taken into consideration by investigators using large volume 3D scaffolds when engineering mechanically sensitive tissues. PMID- 27353292 TI - A metagenomic-based survey of microbial (de)halogenation potential in a German forest soil. AB - In soils halogens (fluorine, chlorine, bromine, iodine) are cycled through the transformation of inorganic halides into organohalogen compounds and vice versa. There is evidence that these reactions are microbially driven but the key enzymes and groups of microorganisms involved are largely unknown. Our aim was to uncover the diversity, abundance and distribution of genes encoding for halogenating and dehalogenating enzymes in a German forest soil by shotgun metagenomic sequencing. Metagenomic libraries of three soil horizons revealed the presence of genera known to be involved in halogenation and dehalogenation processes such as Bradyrhizobium or Pseudomonas. We detected a so far unknown diversity of genes encoding for (de)halogenating enzymes in the soil metagenome including specific and unspecific halogenases as well as metabolic and cometabolic dehalogenases. Genes for non-heme, no-metal chloroperoxidases and haloalkane dehalogenases were the most abundant halogenase and dehalogenase genes, respectively. The high diversity and abundance of (de)halogenating enzymes suggests a strong microbial contribution to natural halogen cycling. This was also confirmed in microcosm experiments in which we quantified the biotic formation of chloroform and bromoform. Knowledge on microorganisms and genes that catalyze (de)halogenation reactions is critical because they are highly relevant to industrial biotechnologies and bioremediation applications. PMID- 27353293 TI - Endothelin-1 Immunoreactivity and its Association with Intramedullary Hemorrhage and Myelomalacia in Naturally Occurring Disk Extrusion in Dogs. AB - BACKGROUND: The pathophysiology of ascending/descending myelomalacia (ADMM) after canine intervertebral disk (IVD) extrusion remains poorly understood. Vasoactive molecules might contribute. HYPOTHESIS/OBJECTIVES: To investigate the immunoreactivity of endothelin-1 (ET-1) in the uninjured and injured spinal cord of dogs and its potential association with intramedullary hemorrhage and extension of myelomalacia. ANIMALS: Eleven normal control and 34 dogs with thoracolumbar IVD extrusion. METHODS: Spinal cord tissue of dogs retrospectively selected from our histopathologic database was examined histologically at the level of the extrusion (center) and in segments remote from the center. Endothelin-1 immunoreactivity was examined immunohistochemically and by in situ hybridization. Associations between the immunoreactivity for ET-1 and the severity of intramedullary hemorrhage or the extension of myelomalacia were examined. RESULTS: Endothelin-1 was expressed by astrocytes, macrophages, and neurons and only rarely by endothelial cells in all dogs. At the center, ET-1 immunoreactivity was significantly higher in astrocytes (median score 4.02) and lower in neurons (3.21) than in control dogs (3.0 and 4.54) (P < .001; P = .004) irrespective of the grade of hemorrhage or myelomalacia. In both astrocytes and neurons, there was a higher ET-1 immunoreactivity in spinal cord regions remote from the center (4.58 and 4.15) than in the center itself (P = .013; P = .001). ET-1 mRNA was present in nearly all neurons with variable intensity, but not in astrocytes. CONCLUSION AND CLINICAL IMPORTANCE: Enhanced ET-1 immunoreactivity over multiple spinal cord segments after IVD extrusion might play a role in the pathogenesis of ADMM. More effective quantitative techniques are required. PMID- 27353294 TI - Early-onset Purkinje cell dysfunction underlies cerebellar ataxia in peroxisomal multifunctional protein-2 deficiency. AB - The cerebellar pathologies in peroxisomal diseases underscore that these organelles are required for the normal development and maintenance of the cerebellum, but the mechanisms have not been resolved. Here we investigated the origins of the early-onset coordination impairment in a mouse model with neural selective deficiency of multifunctional protein-2, the central enzyme of peroxisomal beta-oxidation. At the age of 4weeks, Nestin-Mfp2(-/-) mice showed impaired motor learning on the accelerating rotarod and underperformed on the balance beam test. The gross morphology of the cerebellum and Purkinje cell arborization were normal. However, electrophysiology revealed a reduced Purkinje cell firing rate, a decreased excitability and an increased membrane capacitance. The distribution of climbing and parallel fiber synapses on Purkinje cells was immature and was accompanied by an increased spine length. Despite normal myelination, Purkinje cell axon degeneration was evident from the occurrence of axonal swellings containing accumulated organelles. In conclusion, the electrical activity, axonal integrity and wiring of Purkinje cells are exquisitely dependent on intact peroxisomal beta-oxidation in neural cells. PMID- 27353296 TI - Editorial. PMID- 27353295 TI - Health care utilization and outpatient, out-of-pocket costs for active convulsive epilepsy in rural northeastern South Africa: a cross-sectional Survey. AB - BACKGROUND: Epilepsy is a common neurological disorder, with over 80 % of cases found in low- and middle-income countries (LMICs). Studies from high-income countries find a significant economic burden associated with epilepsy, yet few studies from LMICs, where out-of-pocket costs for general healthcare can be substantial, have assessed out-of-pocket costs and health care utilization for outpatient epilepsy care. METHODS: Within an established health and socio demographic surveillance system in rural South Africa, a questionnaire to assess self-reported health care utilization and time spent traveling to and waiting to be seen at health facilities was administered to 250 individuals, previously diagnosed with active convulsive epilepsy. Epilepsy patients' out-of-pocket, medical and non-medical costs and frequency of outpatient care visits during the previous 12-months were determined. RESULTS: Within the last year, 132 (53 %) individuals reported consulting at a clinic, 162 (65 %) at a hospital and 34 (14 %) with traditional healers for epilepsy care. Sixty-seven percent of individuals reported previously consulting with both biomedical caregivers and traditional healers. Direct outpatient, median costs per visit varied significantly (p < 0.001) between hospital (2010 International dollar ($) 9.08; IQR: $6.41-$12.83) and clinic consultations ($1.74; IQR: $0-$5.58). Traditional healer fees per visit were found to cost $52.36 (IQR: $34.90-$87.26) per visit. Average annual outpatient, clinic and hospital out-of-pocket costs totaled $58.41. Traveling to and from and waiting to be seen by the caregiver at the hospital took significantly longer than at the clinic. CONCLUSIONS: Rural South Africans with epilepsy consult with both biomedical caregivers and traditional healers for both epilepsy and non-epilepsy care. Traditional healers were the most expensive mode of care, though utilized less often. While higher out-of-pocket costs were incurred at hospital visits, more people with ACE visited hospitals than clinics for epilepsy care. Promoting increased use and effective care at clinics and reducing travel and waiting times could substantially reduce the out-of-pocket costs of outpatient epilepsy care. PMID- 27353297 TI - Biomonitoring of heavy metals using bottom fish and crab as bioindicator species, the Arvand River. AB - The main aim of this study was to biomonitor mercury (Hg), arsenic (As), cadmium (Cd), lead (Pb) and copper (Cu) concentrations in the Arvand River using Heteropnestis fossilis and Parasesarma persicum Comparison of heavy metals among the stations indicated that the concentrations of Hg, As, Cd, Cu and Pb in sediment samples were apparently different among the stations. The results of linear regression analyses showed that there were significant correlations (p < 0.05) between Hg, As and Pb elements in sediment and hepatopancreas of P. persicum and between As in sediment and liver of H. fossilis These findings showed that P. persicum could be considered as a biomonitor of Hg, As and Pb and H. fossilis as a biomonitor of As contamination in sediment of the Arvand River. PMID- 27353298 TI - Determining mercury levels in anchovy and in individuals with different fish consumption habits, together with their neurological effects. AB - An increase in enviromental pollution may lead to mercury toxicity of fish origin due to the accumulative nature of methylmercury in fish. The main sources of human exposure to organic mercury compounds are contaminated fish and other seafoods. This descriptive study was planned to determine mercury levels in anchovy and in hair samples from individuals with different fish consumption habits, and to evaluate those individuals in terms of toxic effects. For that purpose, we analyzed 100 anchovies from the Black Sea and 100 anchovies from the Sea of Marmara, and assessed 25 wholesale workers in fish markets and 25 cleaning firm employees from both Ankara and Istanbul. Mercury levels in samples were measured using a cold vapor atomic absorption spectrophotometer. Participants were examined neurologically and mini mental state examination was applied to evaluate their cognitive functions. Mercury levels in fish were found to be below the national and international permitted levels. There was no statistically significant relation between mercury levels and the sea from which fish were caught. Hair mercury levels for all participants were within permitted ranges. However, hair mercury levels in both cities increased significantly with amount and frequency of fish consumption. A significant correlation was determined at correlation analysis between levels of fish consumption and hair mercury levels in the fishmongers and in the entire group (r = 0.32, p = 0.025; r = 0.23, p = 0.023, respectively). Neurological examination results were normal, except for a decrease in deep tendon reflexes in some participants in both cities. There was no correlation between Standardized Mini Mental State Examination results and hair mercury levels. We conclude that establishing a monitoring system for mercury levels in fish and humans will be useful in terms of evaluating potential neurotoxic effects. PMID- 27353299 TI - Protective effect of crocin against apoptosis induced by subchronic exposure of the rat vascular system to diazinon. AB - Research has suggested that natural antioxidant, crocin, an active ingredient of saffron, may protect against diazinon (DZN)-induced toxicity. Although increased production of lipid peroxidation by DZN in rat aorta has been shown previously, the effects of DZN on oxidative stress-induced apoptosis in vascular system have not been evaluated. In this study, the effect of crocin on DZN-induced apoptosis in rat vascular system was investigated. The rats were divided into 7 groups: corn oil (control), DZN (15 mg/kg/day, gavage), crocin (12.5, 25, and 50 mg/kg/day, intraperitoneally (i.p.)) + DZN, vitamin E (200 IU/kg, i.p., 3 days a week) + DZN, and crocin (50 mg/kg/day, i.p.). The treatments were continued for 4 weeks. Levels of apoptotic (Bax, caspase 3, and caspase 9) and antiapoptotic proteins (Bcl2) were analyzed by Western blotting. Transcript levels of Bax and Bcl2 genes were determined using quantitative real-time polymerase chain reaction. Results showed DZN-induced apoptosis by activation of caspase 9 and caspase 3 and by increasing the Bax/Bcl2 ratio (both protein and messenger RNA levels). Crocin and vitamin E inhibited apoptosis induced by DZN. In summary, subchronic exposure to DZN induced caspase-mediated apoptosis, and crocin reduced the toxic effects of DZN by inhibiting apoptosis in aortic tissue. PMID- 27353300 TI - The effect of benzo[alpha]pyrene on expression and signaling cross talk of aryl hydrocarbon receptor and NFATc1 in mouse lung tissue. AB - OBJECTIVE: Polycyclic aromatic hydrocarbons (PAHs) are potent environmental pollutants. Benzo[alpha]pyrene (B[alpha]P) is the major compound of PAHs that acts by activating aryl hydrocarbon receptor (AhR) in cells. B[alpha]P is a known carcinogen and an immunotoxicant; however, its role with regard to nuclear factor of activated T cell (NFAT) pathway is unclear. AhR and NFAT signaling pathways have common roles in pathological functions in immunotoxicity and lung cancer. In this study, the effect of AhR activation on expression and signaling cross talk of AhR and NFATc1 pathways in mouse lung tissue has been investigated. METHODS: Swiss albino mice were randomly allocated to five groups and administered with cyclosporin A (CsA) and B[alpha]P for seven constitutive days. Animals were then killed, and lung tissues were obtained after washing the whole blood. Paraffin embedded blocks were prepared, and 5 um sections were cut for histopathological and immunohistochemical assessments. The results were scored by observer and digitally analyzed using ImageJ software. RESULTS: Our data showed that CsA administration resulted in a significant reduction of AhR expression. This effect was partly blocked in mice coadministrated with B[alpha]P and CsA. NFATc1 expression was also reduced in CsA-treated animals. Furthermore, CsA inhibited the pathological effects of B[alpha]P in mouse lung tissue. CONCLUSION: AhR expression is dependent on NFATc1 activation, and NFATc1 inhibition remarkably decreases AhR expression. However, it seems that total expression of NFATc1 is not dependent on AhR expression or activation. Moreover, CsA can prevent B[alpha]P-induced lung tissue damage, and it remarkably decreases NFATc1 expression. The results from this study point toward the molecular interactions of AhR and NFATc1 activation in lung tissue and the benefit of CsA treatment in B[alpha]P-induced lung damage. PMID- 27353301 TI - Combining machine learning and matching techniques to improve causal inference in program evaluation. AB - RATIONALE, AIMS AND OBJECTIVES: Program evaluations often utilize various matching approaches to emulate the randomization process for group assignment in experimental studies. Typically, the matching strategy is implemented, and then covariate balance is assessed before estimating treatment effects. This paper introduces a novel analytic framework utilizing a machine learning algorithm called optimal discriminant analysis (ODA) for assessing covariate balance and estimating treatment effects, once the matching strategy has been implemented. This framework holds several key advantages over the conventional approach: application to any variable metric and number of groups; insensitivity to skewed data or outliers; and use of accuracy measures applicable to all prognostic analyses. Moreover, ODA accepts analytic weights, thereby extending the methodology to any study design where weights are used for covariate adjustment or more precise (differential) outcome measurement. METHOD: One-to-one matching on the propensity score was used as the matching strategy. Covariate balance was assessed using standardized difference in means (conventional approach) and measures of classification accuracy (ODA). Treatment effects were estimated using ordinary least squares regression and ODA. RESULTS: Using empirical data, ODA produced results highly consistent with those obtained via the conventional methodology for assessing covariate balance and estimating treatment effects. CONCLUSIONS: When ODA is combined with matching techniques within a treatment effects framework, the results are consistent with conventional approaches. However, given that it provides additional dimensions and robustness to the analysis versus what can currently be achieved using conventional approaches, ODA offers an appealing alternative. PMID- 27353302 TI - Why are some cyano-based ionic liquids better glucose solvents than water? AB - Among different classes of ionic liquids (ILs), those with cyano-based anions have been of special interest due to their low viscosity and enhanced solvation ability for a large variety of compounds. Experimental results from this work reveal that the solubility of glucose in some of these ionic liquids may be higher than in water - a well-known solvent with enhanced capacity to dissolve mono- and disaccharides. This raises questions on the ability of cyano groups to establish strong hydrogen bonds with carbohydrates and on the optimal number of cyano groups at the IL anion that maximizes the solubility of glucose. In addition to experimental solubility data, these questions are addressed in this study using a combination of density functional theory (DFT) and molecular dynamics (MD) simulations. Through the calculation of the number of hydrogen bonds, coordination numbers, energies of interaction and radial and spatial distribution functions, it was possible to explain the experimental results and to show that the ability to favorably interact with glucose is driven by the polarity of each IL anion, with the optimal anion being dicyanamide. PMID- 27353303 TI - A systematic review and meta-analysis of the relative efficacy and safety of treatment regimens for HIV-associated cerebral toxoplasmosis: is trimethoprim sulfamethoxazole a real option? AB - OBJECTIVES: The objective of this study was to perform a systematic review and meta-analysis of the literature to evaluate the efficacy and safety of therapies for cerebral toxoplasmosis in HIV-infected adults. The pyrimethamine plus sulfadiazine (P-S) combination is considered the mainstay therapy for cerebral toxoplasmosis and pyrimethamine plus clindamycin (P-C) is the most common alternative treatment. Although trimethoprim-sulfamethoxazole (TMP-SMX) has potential advantages, its use is infrequent. METHODS: We searched PubMed and four other databases to identify randomized controlled trials (RCTs) and cohort studies. Two independent reviewers searched the databases, identified studies and extracted data. Risk ratios (RRs) were pooled across studies using random-effects models. RESULTS: Nine studies were included (five RCTs, three retrospective cohort studies and one prospective cohort study). In comparison to P-S, treatment with P-C or TMP-SMX was associated with similar rates of partial or complete clinical response [P-C: RR 0.87; 95% confidence interval (CI) 0.70-1.08; TMP-SMX: RR 0.97; 95% CI 0.78-1.21], radiological response (P-C: RR 0.92; 95% CI 0.82 1.03), skin rash (P-C: RR 0.81; 95% CI 0.56-1.17; TMP-SMX: RR 0.17; 95% CI 0.02 1.29), gastrointestinal impairment (P-C: RR 5.16; 95% CI 0.66-40.11), and drug discontinuation because of adverse events (P-C: RR 0.32; 95% CI 0.07-1.47). Liver impairment was more frequent with P-S than P-C (P-C vs. P-S: RR 0.48; 95% CI 0.24 0.97). CONCLUSIONS: The current evidence fails to identify a superior regimen in terms of relative efficacy or safety for the treatment of HIV-associated cerebral toxoplasmosis. Use of TMP-SMX as preferred treatment may be consistent with the available evidence and other real-world considerations. Larger comparative studies are needed. PMID- 27353304 TI - Family history and perceived risk of diabetes, cardiovascular disease, cancer, and depression. AB - BACKGROUND: Family history is a useful and inexpensive tool to assess risks of multifactorial diseases. Family history enables individualized disease prevention, but its effects on perceived risks of various diseases need to be understood in more detail. We examined how family history relates to perceived risk of diabetes mellitus, cardiovascular disease (CVD), cancer, and depression, and whether these associations are independent of or moderated by sociodemographic factors, health behavior/weight status (smoking, alcohol consumption, physical activity, BMI [kg/m(2)]), or depressive symptoms. METHODS: Participants were Finnish 25-74-year-olds (N=6258) from a population-based FINRISK 2007 study. Perceived absolute lifetime risks (Brewer et al., 2004; Becker, 1974; Weinstein and Nicolich, 1993; Guttmacher et al., 2004; Yoon et al., 2002) and first-degree family history of CVD, diabetes, cancer and depression, and health behaviors were self-reported. Weight and height were measured in a health examination. RESULTS: Family history was most prevalent for cancer (36.7%), least for depression (19.6%). Perceived risk mean was highest for CVD (2.8), lowest for depression (2.0). Association between family history and perceived risk was strongest for diabetes (beta=0.34, P<0.001), weakest for depression (beta=0.19, P<0.001). Adjusting for sociodemographics, health behavior, and depressive symptoms did not change these associations. The association between family history and perceived risk tended to be stronger among younger than among older adults, but similar regardless of health behaviors or depressive symptoms. DISCUSSION: Association between family history and perceived risk varies across diseases. People's current understandings on heritability need to be acknowledged in risk communication practices. Future research should seek to identify effective strategies to combine familial and genetic risk communication in disease prevention. PMID- 27353307 TI - How do levels of nursing home adjustment differ by length of stay? AB - The purpose of this study was to explore how residents' adjustment is different depending on the length of stay in nursing homes. A total of 161 cognitively intact residents completed a survey questionnaire of the Nursing Home Adjustment Scale (NHAS) and demographic information. Controlling for activities of daily living function, a generalized linear model demonstrated that the levels of nursing home adjustment are different depending on the length of stay for nursing home residents. Residents who stayed 12 months or more (Groups 4 or 5) showed the highest NHAS scores, followed by the group who stayed under 3 months (Groups 1 or 2), and those who stayed 3 months or more but under 12 months (Group 3) had the lowest NHAS scores. Knowing that residents' life adjustment might vary based on the length of stay, nursing home staff can identify residents' level of adjustment, predict their needs and implement interventions in a timely manner. PMID- 27353306 TI - Role of Cl- -HCO3- exchanger AE3 in intracellular pH homeostasis in cultured murine hippocampal neurons, and in crosstalk to adjacent astrocytes. AB - KEY POINTS: A polymorphism of human AE3 is associated with idiopathic generalized epilepsy. Knockout of AE3 in mice lowers the threshold for triggering epileptic seizures. The explanations for these effects are elusive. Comparisons of cells from wild-type vs. AE3-/- mice show that AE3 (present in hippocampal neurons, not astrocytes; mediates HCO3- efflux) enhances intracellular pH (pHi ) recovery (decrease) from alkali loads in neurons and, surprisingly, adjacent astrocytes. During metabolic acidosis (MAc), AE3 speeds initial acidification, but limits the extent of pHi decrease in neurons and astrocytes. AE3 speeds re-alkalization after removal of MAc in neurons and astrocytes, and speeds neuronal pHi recovery from an ammonium prepulse-induced acid load. We propose that neuronal AE3 indirectly increases acid extrusion in (a) neurons via Cl- loading, and (b) astrocytes by somehow enhancing NBCe1 (major acid extruder). The latter would enhance depolarization-induced alkalinization of astrocytes, and extracellular acidification, and thereby reduce susceptibility to epileptic seizures. ABSTRACT: The anion exchanger AE3, expressed in hippocampal (HC) neurons but not astrocytes, contributes to intracellular pH (pHi ) regulation by facilitating the exchange of extracellular Cl- for intracellular HCO3- . The human AE3 polymorphism A867D is associated with idiopathic generalized epilepsy. Moreover, AE3 knockout (AE3-/- ) mice are more susceptible to epileptic seizure. The mechanism of these effects has been unclear because the starting pHi in AE3-/- and wild-type neurons is indistinguishable. The purpose of the present study was to use AE3-/- mice to investigate the role of AE3 in pHi homeostasis in HC neurons, co-cultured with astrocytes. We find that the presence of AE3 increases the acidification rate constant during pHi recovery from intracellular alkaline loads imposed by reducing [CO2 ]. The presence of AE3 also speeds intracellular acidification during the early phase of metabolic acidosis (MAc), not just in neurons but, surprisingly, in adjacent astrocytes. Additionally, AE3 contributes to braking the decrease in pHi later during MAc in both neurons and astrocytes. Paradoxically, AE3 enhances intracellular re-alkalization after MAc removal in neurons and astrocytes, and pHi recovery from an ammonium prepulse-induced acid load in neurons. The effects of AE3 knockout on astrocytic pHi homeostasis in MAc related assays require the presence of neurons, and are consistent with the hypothesis that the AE3 knockout reduces functional expression of astrocytic NBCe1. These findings suggest a new type of neuron-astrocyte communication, based on the expression of AE3 in neurons, which could explain how AE3 reduces seizure susceptibility. PMID- 27353308 TI - A Lack of Serotonin 1B Autoreceptors Results in Decreased Anxiety and Depression Related Behaviors. AB - The effects of serotonin (5-HT) on anxiety and depression are mediated by a number of 5-HT receptors, including autoreceptors that act to inhibit 5-HT release. While the majority of anxiety and depression-related research has focused on the 5-HT1A receptor, the 5-HT1B receptor has a lesser known role in modulating emotional behavior. 5-HT1B receptors are inhibitory GPCRs located on the presynaptic terminal of both serotonin and non-serotonin neurons, where they act to inhibit neurotransmitter release. The autoreceptor population located on the axon terminals of 5-HT neurons is a difficult population to study due to their diffuse localization throughout the brain that overlaps with 5-HT1B heteroreceptors (receptors located on non-serotonergic neurons). In order to study the contribution of 5-HT1B autoreceptors to anxiety and depression-related behaviors, we developed a genetic mouse model that allows for selective ablation of 5-HT1B autoreceptors. Mice lacking 5-HT1B autoreceptors displayed the expected increases in extracellular serotonin levels in the ventral hippocampus following administration of a selective serotonin reuptake inhibitor. In behavioral studies, they displayed decreased anxiety-like behavior in the open field and antidepressant-like effects in the forced swim and sucrose preference tests. These results suggest that strategies aimed at blocking 5-HT1B autoreceptors may be useful for the treatment of anxiety and depression. PMID- 27353309 TI - Heightened Dopaminergic Response to Amphetamine at the D3 Dopamine Receptor in Methamphetamine Users. AB - Neuroimaging studies in stimulant use (eg, cocaine, methamphetamine) disorders show that diminished dopamine release by dopamine-elevating drugs is a potential marker of relapse and suggest that increasing dopamine at the D2/3 receptors may be therapeutically beneficial. In contrast, recent investigations indicate heightened D3 receptor levels in stimulant users prompting the view that D3 antagonism may help prevent relapse. Here we tested whether a 'blunted' response to amphetamine in methamphetamine (MA) users extends to D3-rich brain areas. Fourteen MA users and 15 healthy controls completed two positron emission tomographic scans with a D3-preferring probe [11C]-(+)-PHNO at baseline and after amphetamine (0.4 mg/kg). Relative to healthy controls, MA users had greater decreases in [11C]-(+)-PHNO binding (increased dopamine release) after amphetamine in D3-rich substantia nigra (36 vs 20%, p=0.03) and globus pallidus (30 vs 17%, p=0.06), which correlated with self-reported 'drug wanting'. We did not observe a 'blunted' dopamine response to amphetamine in D2-rich striatum; however, drug use severity was negatively associated with amphetamine-induced striatal changes in [11C]-(+)-PHNO binding. Our study provides evidence that dopamine transmission in extrastriatal 'D3-areas' is not blunted but rather increased in MA users. Together with our previous finding of elevated D3 receptor level in MA users, the current observation suggests that greater dopaminergic transmission at the D3 dopamine receptor may contribute to motivation to use drugs and argues in favor of D3 antagonism as a possible therapeutic tool to reduce craving and relapse in MA addiction. PMID- 27353310 TI - GSK3beta Hyperactivity during an Early Critical Period Impairs Prefrontal Synaptic Plasticity and Induces Lasting Deficits in Spine Morphology and Working Memory. AB - Schizophrenia (SZ) is a neurodevelopmental disorder in which the emergence of cognitive symptoms occurs during early adolescence. Glycogen synthase kinase 3beta (GSK3beta) plays a critical role in synaptic plasticity during development and is highly implicated in the etiology of SZ. However, how GSK3beta activity affects synaptic plasticity and working memory function in the prefrontal cortex (PFC) during development remains unknown. Here we show a GSK3beta hyperactivity during the early postnatal period in a neurodevelopmental rat SZ model that receives gestational exposure (E17) to the neurotoxin methylazoxymethanol (MAM). Accompanied with this change, adult MAM rats exhibited a significant decrease in spine density as well as impaired working memory, which was rescued by treatment with a GSK3beta inhibitor during the juvenile period. Furthermore, the age dependent hyperactive GSK3beta caused a significant deficit in long-term potentiation (LTP) and facilitated long-term depression (LTD) in PFC pyramidal neurons. Notably, these changes in synaptic plasticity occurred only during the late juvenile period and were efficiently reversed by application of GSK3beta inhibitors. Because the balance of LTP and LTD plays a critical role in activity dependent synaptic stabilization and elimination during cortical development, the transient hyperactive GSK3beta likely accounts for the cortical spine loss and PFC-dependent cognitive deficits in adulthood. These results highlight the importance of the postnatal trajectory of GSK3beta for spine development and PFC function, and may shed light on the prophylactic treatment of cognitive symptoms in the SZ. PMID- 27353311 TI - Total joint replacement in haemophilia A patients with high titre of inhibitor using a new brand recombinant factor VIIa (Aryoseven((r)) ). PMID- 27353312 TI - Caring with evidence based medicine. PMID- 27353313 TI - Pyropia yezoensis glycoprotein promotes the M1 to M2 macrophage phenotypic switch via the STAT3 and STAT6 transcription factors. AB - Macrophage polarization has been well documented. Macrophages can aquire two phenotypes, the pro-inflammatory M1 phenotype, and the anti-inflammatory and wound healing M2 phenotype. The M1 macrophage phenotype has been linked to metabolic disease and is also associated with cancer-related inflammation. Of note, macrophage polarization can be influenced by the extracellular environment. In the current study, we examined the effects of Pyropia yezoensis glycoprotein (PYGP) on M1 to M2 macrophage polarization in lipopolysaccharide (LPS)-stimulated macrophages. RAW 264.7 macrophages stimulated with LPS exhibited an upregulated expression of pro-inflammatory mediators, namely of the M1 markers, nitric oxide (NO), reactive oxygen species (ROS), interleukin (IL)-6, IL-1beta, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and nitric oxide synthase 2 (NOS-2). Treatment with PYGP inhibited the production of M1 markers and increased arginase 1 (ARG1), chitinase-like 3 (Chil3; also known as Ym1), resistin like beta (RETNLB; also known as FIZZ1), IL-10, CD163, CD206, peroxisome proliferator-activated receptor gamma (PPARgamma) and Kruppel-like factor 4 (KLF4) M2 marker gene expression. The signal transducer and activator of transcription (STAT)3 and STAT6 transcription factors were phosphorylated following treatment with PYGP. However, the silencing of STAT3 and STAT6 using siRNA in the macrophages decreased ARG1, Ym1 and FIZZ1 M2 marker gene expression in spite of treatment of PYGP. These findings suggest that PYGP exerts anti inflammatory effects by regulating the M1 to M2 phenotypic switch through STAT3 and STAT6. Thus, PYGP may have potential for use as a natural remedy for inflammatory diseases. PMID- 27353314 TI - Threshold for surgery to reduce ovarian cancer risk should be lowered, suggests study. PMID- 27353315 TI - Enhancing inhibitory learning to reduce overeating: Design and rationale of a cue exposure therapy trial in overweight and obese women. AB - The prevalence of overweight and obesity has increased substantially over the last decades. Weight loss attempts in overweight individuals are common, though they seldom result in successful long-term weight loss. One very promising treatment is food cue exposure therapy, during which overweight individuals are repeatedly exposed to food-associated cues (e.g., the sight, smell and taste of high-calorie foods, overeating environments) without eating in order to extinguish cue-elicited appetitive responses to food cues. However, only few studies have tested the effectiveness of cue exposure, especially with regards to weight loss. For exposure treatment of anxiety disorders, it has been proposed that inhibitory learning is critical for exposure to be effective. In this RCT, we translated techniques proposed by Craske et al. (2014) to the appetitive domain and developed a novel cue exposure therapy for overeating aimed at maximizing inhibitory learning. The current RCT tested the effectiveness of this 8-session cue exposure intervention relative to a control intervention in 45 overweight adult (aged 18-60) females at post-treatment and 3-month follow-up, of which 39 participants completed the study. Weight loss, eating psychopathology, food cue reactivity, and snacking behaviour were studied as main treatment outcomes, and mediators and moderators of treatment effects were studied. The presented study design represents an innovative effort to provide valuable clinical recommendations for the treatment of overeating and obesity. PMID- 27353316 TI - sigma(E) -dependent activation of RbpA controls transcription of the furA-katG operon in response to oxidative stress in mycobacteria. AB - Mycobacterium tuberculosis adopts various strategies to cope with oxidative stress during infection. Transcriptional regulators, including sigma factors, make important contributions to this stress response, but how these proteins cooperate with each other is largely unknown. In this study, the role of RbpA and its cooperation with sigma factors in response to oxidative stress are investigated. Knock down expression of rbpA in Mycobacterium smegmatis attenuated bacterial survival in the presence of H2 O2 . Additionally, transcription of the rbpA gene was induced by H2 O2 in a sigma(E) -dependent manner. After induction, RbpA interacts with the principal sigma factor, sigma(A) , to control the transcription of furA-katG operon, which encodes an H2 O2 scavenging enzyme. Moreover, this regulation is responsible for the role of sigma(E) in oxidative response because bacterial survival was attenuated and transcription of the furA katG operon was down-regulated with H2 O2 treatment in sigE deletion mutant (DeltasigE), and over-expression of RbpA in DeltasigE strain restored all of these phenotypes. Taken together, our study first illustrated a mechanism for sigma(E) in response to oxidative stress through regulation of rbpA transcription. This study was also the first to demonstrate that RbpA is required for the full response to oxidative stress by cooperating with the principal sigma(A) . PMID- 27353317 TI - Understanding the mechanisms underpinning health inequalities: lessons from economics. PMID- 27353319 TI - Epidermal growth factor receptor is overexpressed in neuroblastoma tissues and cells. AB - Neuroblastoma is the most common abdominal malignant tumor in childhood. Immunotoxin (IT) that targets the tumor cell surface receptor is a new supplementary therapeutic treatment approach. The purpose of this study is to detect the expression of epidermal growth factor receptor (EGFR) in neuroblastoma cell lines and tissues, and to explore if IT therapy can be used to treat refractory neuroblastoma. The EGFR expression in human neuroblastoma tissue samples was detected by immunohistochemistry staining. The positive rate of EGFR expression was 81.0% in neuroblastoma tissue and 50.0% in gangliocytoma, respectively, but without statistical significance between them (P > 0.05). The positive rate of EGFR expression in favorable type and unfavorable type was 62.5% and 92.3%, respectively, but they were not statistically different (P > 0.05). Results from pre-chemotherapy and post-chemotherapy samples showed that there was no significant statistical difference (P > 0.05) between them in the EGFR expression. Furthermore, the EGFR expression levels in five neuroblastoma cell lines were measured using cell-based ELISA assay and western blot analysis. The results showed that the expression of EGFR was higher in KP-N-NS and BE(2)-C than those in other cell lines. Our results revealed that there are consistent and widespread expressions of EGFR in neuroblastoma tissues as well as in neuroblastoma cell lines, suggesting that it is possible to develop future treatment strategies of neuroblastoma by targeting at the EGFR. PMID- 27353320 TI - Cathelicidin PR-39 peptide inhibits hypoxia/reperfusion-induced kidney cell apoptosis by suppression of the endoplasmic reticulum-stress pathway. AB - Ischemia/reperfusion injury (IRI) is a major cause of acute kidney damage, which often occurs in deceased donor kidney transplants. Cathelicidin PR-39 peptide possesses anti-inflammatory and wound repair effects through tissue angiogenesis and anti-apoptosis. This study assessed the role of PR-39 in anti-apoptosis in vitro using a lentiviral vector with a kidney specific promoter (KSP) to drive PR 39 expression. Our data revealed that PR-39 peptide was specifically over expressed in kidney-derived HK-2 cells, but was scarcely detected in non-kidney tissue-derived cells. PR-39 over-expression had a protective role in the hypoxia/re-oxygenation (H/R) treated cells. The anti-apoptotic activity of PR-39 peptide was mediated by the inhibition of caspase-2, caspase-12 and caspase-3 activity in the endoplasmic reticulum (ER) stress-induced apoptotic pathway. It was also revealed that the anti-apoptotic effect of PR-39 peptide was mediated by an apoptosis-related protein, cellular inhibitor apoptosis protein-2 (c-IAP-2). Taken together, the current data demonstrate that PR-39 expression driven by KSP could prevent kidney damage (apoptosis) from IRI via the ER stress-induced apoptotic pathway. PMID- 27353321 TI - Diagnosis and management of iatrogenic cardiac perforation caused by pacemaker and defibrillator leads. AB - Aims: Cardiac perforations caused by pacemaker or implantable cardioverter defibrillator (ICD) leads are uncommon but potentially fatal events. The optimal approach to such cases is unclear. The aim of this study was to identify the optimal imaging modality and management strategy for cardiac perforation. Methods and results: All patients presenting to a single institution with cardiac perforation >24 h since implant between 2011 and 2015 were identified retrospectively. Assessment of the diagnostic performance of pre-extraction chest radiography, transthoracic echocardiography (TTE), and computed tomography (CT) was carried out by blinded review. The method of lead extraction and any associated complications were examined. Eighteen cases of cardiac perforation were identified from 426 lead extraction procedures. Sixteen patients had abnormal electrical parameters at device interrogation. In all cases, the perforating lead was an active fixation model, and in four cases, this was an ICD coil. The accuracy of CT imaging for the diagnosis of cardiac perforation was 92.9%, with sensitivity and specificity of 100 and 85.7%, respectively. This was superior to both TTE (accuracy 62.7%, sensitivity and specificity 41.2 and 84.2%, respectively) and chest radiography (accuracy 61.1%, sensitivity and specificity 27.7 and 94.4%, respectively). Transvenous lead extraction (TLE) was performed in 17 patients, and a hybrid surgical approach in 1 patient. Of those who underwent TLE, there was 100% complete procedural success as per Heart Rhythm Society definitions. Conclusion: In the setting of cardiac perforation, CT is the imaging modality of choice. Transvenous lead extraction can be recommended as a safe, efficacious, and versatile intervention. PMID- 27353322 TI - Long-term benefit of first-line peri-implantable cardioverter-defibrillator implant ventricular tachycardia-substrate ablation in secondary prevention patients. AB - Aims: This study assessed the benefit of peri-implantable cardioverter defibrillator implant ventricular tachycardia (VT)-substrate ablation in patients with structural heart disease (SHD). Methods and results: Patients with SHD and indication for secondary prevention ICD implant were prospectively included. Patients presenting with incessant and/or slow VT or frequent (>=2) VT episodes who underwent peri-ICD VT-substrate ablation (the scar dechannelling technique) were compared with those who received ICD alone and did not meet ablation criteria. The primary endpoint was any sustained VT/ICD therapy during follow-up. Of 206 patients included (43.2% non-ischaemic), 70 were assigned to ablation and 136 received ICD implant alone. During a mean follow-up of 45.6 +/- 24.7 months, the primary endpoint was more frequent in the non-ablation group (47.1 vs. 22.9%; P< 0.0001). Higher VT recurrence-free survival rate [log-rank P= 0.001; HR = 0.42 (0.24-0.73), P= 0.002] and ICD shock-free survival rate [log-rank P= 0.007; HR = 0.36 (0.17-0.78); P = 0.01] were observed in the ablation group. Higher relative risk reduction was observed in ischaemic [HR = 0.38 (0.18-0.83); P = 0.015] vs. non-ischaemic patients [HR = 0.49 (0.23-1.01); P = 0.08]. Patients with left ventricular ejection fraction (LVEF) <35% showed no differences in VT recurrence between treatment groups (log-rank P = 0.213) although VT burden during follow-up was lower in the ablation group [median (interquartile range) 1 (1-3) vs. 4 (1 10) VT episodes; P = 0.05]. Conclusion: First-line peri-ICD implant VT-substrate ablation was associated with decreased VT recurrence and ICD shocks during long term follow-up in patients with SHD and indication for secondary prevention ICD implant, especially in ischaemic patients. In patients with LVEF <35%, no benefit was observed in terms of VT recurrence-free survival, although VT burden during follow-up was lower in the ablation group. PMID- 27353323 TI - Wound haematoma following defibrillator implantation: incidence and predictors in the Shockless Implant Evaluation (SIMPLE) trial. AB - Aims: Pocket haematoma is a common complication after defibrillator [implantable cardioverter defibrillator (ICD)] implantation, which is not only painful, but also increases the risk of device-related infection, and possibly embolic events. The present study seeks to evaluate the rate and predictors of clinically significant pocket haematoma. Methods and results: This study included 2500 patients receiving an ICD in the SIMPLE trial. A clinically significant pocket haematoma was defined as a haematoma that required re-operation or interruption of oral anticoagulation (OAC) therapy. Clinically significant pocket haematoma occurred in 56 of 2500 patients (2.2%) of which 6 (10.7%) developed device related infection. Patients who developed pocket haematoma were older (mean age 67.6 +/- 8.8 years vs. 62.7 +/- 11.6 years, P < 0.001), were more likely to have permanent atrial fibrillation (30.4 vs. 6.7%, P < 0.001) and a history of stroke (17.9 vs. 6.7%, P = 0.004), or were more likely to receive peri-operative OAC (50.0 vs. 28.4%, P < 0.001), unfractionated heparin (16.1 vs. 5.2%, P = 0.003), or low-molecular-weight heparin (37.5 vs. 17.5%, P < 0.001). Independent predictors of wound haematoma on multivariable analysis included the use of heparin bridging (OR 2.65, 95% CI 1.48-4.73, P = 0.001), sub-pectoral location of ICD (OR 2.00, 95% CI 1.12-3.57, P =0.020), previous stroke (OR 2.47, 95% CI 1.20 5.10, P = 0.015), an upgrade from permanent pacemaker (OR 2.52, 95% CI 1.07-5.94, P = 0.035), and older age (OR 1.03, 95% CI 1.00-1.06, P = 0.049). Conclusion: Pocket haematoma remains an important complication of ICD implantation and is associated with a high risk of infection. Independent predictors of pocket haematoma include heparin bridging, prior stroke, sub-pectoral placement of ICD, older age, and upgrade from a pacemaker. PMID- 27353324 TI - Impact of surround flow catheter tip irrigation in contact force ablation on the incidence of asymptomatic oesophageal lesions after atrial fibrillation ablation: a prospective comparative study. AB - Aims: Aim of this study was to evaluate the impact of a recently introduced contact force ablation catheter with modified irrigation technology compared with a conventionally irrigated ablation catheter on the incidence of endoscopically detected oesophageal lesions (EDEL). Methods and results: Patients with symptomatic, drug-refractory paroxysmal or persistent atrial fibrillation (AF) who underwent left atrial radiofrequency (RF) catheter ablation were prospectively enrolled. Patients were ablated using a single-tip RF contact force ablation catheter with conventional irrigation (Group 1; n = 50) or with a recently introduced intensified 'surround flow' irrigation technology (Group 2; n = 50). Assessment of EDEL was performed by oesophagogastroduodenoscopy in all patients after ablation. A total of 100 patients (mean age 63.6 +/- 12.1 years; men 58%) with paroxysmal (n = 41; 41%) or persistent AF were included. Groups 1 and 2 patients were comparable in regard to baseline characteristics and procedural parameters, especially ablation time at posterior left atrial wall. Overall, 13 patients (13%) developed EDEL after AF ablation (8 oesophageal ulcerations, 5 erythema). The incidence of EDEL including oesophageal ulcerations was higher in Group 2 compared with Group 1 patients without statistical significance (18 vs. 8%, P = 0.23). One pericardial tamponade and one access site bleeding occurred in Group 2. No further adverse events were reported in both groups. Conclusion: According to these preliminary results, the use of an improved ablation catheter irrigation technology (surround flow) in conjunction with contact force measurement was associated with a higher but not statistically significant probability of oesophageal thermal lesions. Further studies including larger patient cohorts are needed. PMID- 27353325 TI - Long-term outcomes after event-free cardioverter defibrillator implantation: comparison between patients discharged within 24 h and routinely hospitalized patients in the German DEVICE registry. AB - Aims: To analyse the long-term safety of implantable cardioverter defibrillators (ICDs) in patients discharged within 24 h or after 2- 5-day hospitalization, respectively, after complication-free implantation, in circumstances of actual care. Methods and results: Patients in the multicentre, nationwide German DEVICE registry were contacted 12-15 months after their first ICD implantation or device replacement. Data were collected on complications, potential arrhythmic events, syncope, resuscitation, ablation procedures, cardiac events, hospitalizations, heart failure status, change of medication, and quality of life. Of 2356 patients from 43 centres, 527 patients were discharged within 24 h and 1829 were hospitalized routinely for >24 h after complication-free implantations. The disease profiles and rates of co-morbidities were similar at baseline for both cohorts. During between 384 and 543 days of follow-up, there were no significant differences between the groups in terms of complications, hospitalizations, or quality of life. One-year rates of death were 4.5% in patients discharged early compared with 7.2% in hospitalized patients (hazard ratio 0.65; 95% confidence interval 0.42-1.02; P = 0.052). Rates of major adverse cardiovascular events or defibrillator events were not higher in patients discharged after 24 h. In both groups, a high rate of patients declared that they would opt for the procedure again in the same situation. Conclusion: Data from a large-scale registry reflecting current day-to-day practice in Germany suggest that most patients can be discharged safely within 24 h of successful ICD implantation if there are no procedure-related events. Follow-up data up to 1.5 years after implantation did not raise long-term safety concerns. PMID- 27353326 TI - Multiple P-TEFbs cooperatively regulate the release of promoter-proximally paused RNA polymerase II. AB - The association of DSIF and NELF with initiated RNA Polymerase II (Pol II) is the general mechanism for inducing promoter-proximal pausing of Pol II. However, it remains largely unclear how the paused Pol II is released in response to stimulation. Here, we show that the release of the paused Pol II is cooperatively regulated by multiple P-TEFbs which are recruited by bromodomain-containing protein Brd4 and super elongation complex (SEC) via different recruitment mechanisms. Upon stimulation, Brd4 recruits P-TEFb to Spt5/DSIF via a recruitment pathway consisting of Med1, Med23 and Tat-SF1, whereas SEC recruits P-TEFb to NELF-A and NELF-E via Paf1c and Med26, respectively. P-TEFb-mediated phosphorylation of Spt5, NELF-A and NELF-E results in the dissociation of NELF from Pol II, thereby transiting transcription from pausing to elongation. Additionally, we demonstrate that P-TEFb-mediated Ser2 phosphorylation of Pol II is dispensable for pause release. Therefore, our studies reveal a co-regulatory mechanism of Brd4 and SEC in modulating the transcriptional pause release by recruiting multiple P-TEFbs via a Mediator- and Paf1c-coordinated recruitment network. PMID- 27353327 TI - Prior knowledge transfer across transcriptional data sets and technologies using compositional statistics yields new mislabelled ovarian cell line. AB - Here, we describe gene expression compositional assignment (GECA), a powerful, yet simple method based on compositional statistics that can validate the transfer of prior knowledge, such as gene lists, into independent data sets, platforms and technologies. Transcriptional profiling has been used to derive gene lists that stratify patients into prognostic molecular subgroups and assess biomarker performance in the pre-clinical setting. Archived public data sets are an invaluable resource for subsequent in silico validation, though their use can lead to data integration issues. We show that GECA can be used without the need for normalising expression levels between data sets and can outperform rank-based correlation methods. To validate GECA, we demonstrate its success in the cross platform transfer of gene lists in different domains including: bladder cancer staging, tumour site of origin and mislabelled cell lines. We also show its effectiveness in transferring an epithelial ovarian cancer prognostic gene signature across technologies, from a microarray to a next-generation sequencing setting. In a final case study, we predict the tumour site of origin and histopathology of epithelial ovarian cancer cell lines. In particular, we identify and validate the commonly-used cell line OVCAR-5 as non-ovarian, being gastrointestinal in origin. GECA is available as an open-source R package. PMID- 27353328 TI - Optimizing sgRNA position markedly improves the efficiency of CRISPR/dCas9 mediated transcriptional repression. AB - CRISPR interference (CRISPRi) represents a newly developed tool for targeted gene repression. It has great application potential for studying gene function and mapping gene regulatory elements. However, the optimal parameters for efficient single guide RNA (sgRNA) design for CRISPRi are not fully defined. In this study, we systematically assessed how sgRNA position affects the efficiency of CRISPRi in human cells. We analyzed 155 sgRNAs targeting 41 genes and found that CRISPRi efficiency relies heavily on the precise recruitment of the effector complex to the target gene transcription start site (TSS). Importantly, we demonstrate that the FANTOM5/CAGE promoter atlas represents the most reliable source of TSS annotations for this purpose. We also show that the proximity to the FANTOM5/CAGE defined TSS predicts sgRNA functionality on a genome-wide scale. Moreover, we found that once the correct TSS is identified, CRISPRi efficiency can be further improved by considering sgRNA sequence preferences. Lastly, we demonstrate that CRISPRi sgRNA functionality largely depends on the chromatin accessibility of a target site, with high efficiency focused in the regions of open chromatin. In summary, our work provides a framework for efficient CRISPRi assay design based on functionally defined TSSs and features of the target site chromatin. PMID- 27353329 TI - Blue light-mediated transcriptional activation and repression of gene expression in bacteria. AB - Light-regulated modules offer unprecedented new ways to control cellular behavior in precise spatial and temporal resolution. The availability of such tools may dramatically accelerate the progression of synthetic biology applications. Nonetheless, current optogenetic toolbox of prokaryotes has potential issues such as lack of rapid and switchable control, less portable, low dynamic expression and limited parts. To address these shortcomings, we have engineered a novel bidirectional promoter system for Escherichia coli that can be induced or repressed rapidly and reversibly using the blue light dependent DNA-binding protein EL222. We demonstrated that by modulating the dosage of light pulses or intensity we could control the level of gene expression precisely. We show that both light-inducible and repressible system can function in parallel with high spatial precision in a single cell and can be switched stably between ON- and OFF states by repetitive pulses of blue light. In addition, the light-inducible and repressible expression kinetics were quantitatively analysed using a mathematical model. We further apply the system, for the first time, to optogenetically synchronize two receiver cells performing different logic behaviors over time using blue light as a molecular clock signal. Overall, our modular approach layers a transformative platform for next-generation light-controllable synthetic biology systems in prokaryotes. PMID- 27353330 TI - SLIRP stabilizes LRPPRC via an RRM-PPR protein interface. AB - LRPPRC is a protein that has attracted interest both for its role in post transcriptional regulation of mitochondrial gene expression and more recently because numerous mutated variants have been characterized as causing severe infantile mitochondrial neurodegeneration. LRPPRC belongs to the pentatricopeptide repeat (PPR) protein family, originally defined by their RNA binding capacity, and forms a complex with SLIRP that harbours an RNA recognition motif (RRM) domain. We show here that LRPPRC displays a broad and strong RNA binding capacity in vitro in contrast to SLIRP that associates only weakly with RNA. The LRPPRC-SLIRP complex comprises a hetero-dimer via interactions by polar amino acids in the single RRM domain of SLIRP and three neighbouring PPR motifs in the second quarter of LRPPRC, which critically contribute to the LRPPRC-SLIRP binding interface to enhance its stability. Unexpectedly, specific amino acids at this interface are located within the PPRs of LRPPRC at positions predicted to interact with RNA and within the RNP1 motif of SLIRP's RRM domain. Our findings thus unexpectedly establish that despite the prediction that these residues in LRPPRC and SLIRP should bind RNA, they are instead used to facilitate protein protein interactions, enabling the formation of a stable complex between these two proteins. PMID- 27353331 TI - Homology directed repair is unaffected by the absence of siRNAs in Drosophila melanogaster. AB - Small interfering RNAs (siRNAs) defend the organism against harmful transcripts from exogenous (e.g. viral) or endogenous (e.g. transposons) sources. Recent publications describe the production of siRNAs induced by DNA double-strand breaks (DSB) in Neurospora crassa, Arabidopsis thaliana, Drosophila melanogaster and human cells, which suggests a conserved function. A current hypothesis is that break-induced small RNAs ensure efficient homologous recombination (HR). However, biogenesis of siRNAs is often intertwined with other small RNA species, such as microRNAs (miRNAs), which complicates interpretation of experimental results. In Drosophila, siRNAs are produced by Dcr-2 while miRNAs are processed by Dcr-1. Thus, it is possible to probe siRNA function without miRNA deregulation. We therefore examined DNA double-strand break repair after perturbation of siRNA biogenesis in cultured Drosophila cells as well as mutant flies. Our assays comprised reporters for the single-strand annealing pathway, homologous recombination and sensitivity to the DSB-inducing drug camptothecin. We could not detect any repair defects caused by the lack of siRNAs derived from the broken DNA locus. Since production of these siRNAs depends on local transcription, they may thus participate in RNA metabolism-an established function of siRNAs-rather than DNA repair. PMID- 27353332 TI - Frequent occurrence of large duplications at reciprocal genomic rearrangement breakpoints in multiple myeloma and other tumors. AB - Using a combination of array comparative genomic hybridization, mate pair and cloned sequences, and FISH analyses, we have identified in multiple myeloma cell lines and tumors a novel and recurrent type of genomic rearrangement, i.e. interchromosomal rearrangements (translocations or insertions) and intrachromosomal inversions that contain long (1-4000 kb; median ~100 kb) identical sequences adjacent to both reciprocal breakpoint junctions. These duplicated sequences were generated from sequences immediately adjacent to the breakpoint from at least one-but sometimes both-chromosomal donor site(s). Tandem duplications had a similar size distribution suggesting the possibility of a shared mechanism for generating duplicated sequences at breakpoints. Although about 25% of apparent secondary rearrangements contained these duplications, primary IGH translocations rarely, if ever, had large duplications at breakpoint junctions. Significantly, these duplications often contain super-enhancers and/or oncogenes (e.g. MYC) that are dysregulated by rearrangements during tumor progression. We also found that long identical sequences often were identified at both reciprocal breakpoint junctions in six of eight other tumor types. Finally, we have been unable to find reports of similar kinds of rearrangements in wild type or mutant prokaryotes or lower eukaryotes such as yeast. PMID- 27353333 TI - The aggrecanopathies; an evolving phenotypic spectrum of human genetic skeletal diseases. AB - The large chondroitin sulphated proteoglycan aggrecan (ACAN) is the most abundant non-collagenous protein in cartilage and is essential for its structure and function. Mutations in ACAN result in a broad phenotypic spectrum of non-lethal skeletal dysplasias including spondyloepimetaphyseal dysplasia, spondyloepiphyseal dysplasia, familial osteochondritis dissecans and various undefined short stature syndromes associated with accelerated bone maturation. However, very little is currently known about the disease pathways that underlie these aggrecanopathies, although they are likely to be a combination of haploinsufficiency and dominant-negative (neomorphic) mechanisms. This review discusses the known human and animal aggrecanopathies in the context of clinical presentation and potential disease mechanisms. PMID- 27353334 TI - Bacteriophage cocktail and multi-strain probiotics in the feed for weanling pigs: effects on intestine morphology and targeted intestinal coliforms and Clostridium. AB - Two experiments were conducted to investigate the effects of dietary supplementation of bacteriophage cocktail, probiotics and a combination of these two supplements on performance and gut health of weanling pigs. In Experiment 1, 150 weaned piglets were randomly allotted to three treatments on the basis of BW. The dietary treatments included a basal diet supplemented with 0 (control), 1.0 and 1.5 g/kg bacteriophage cocktail. Pigs fed 1.0 and 1.5 g/kg bacteriophage product had greater (P<0.05) average daily gain (ADG), apparent total tract digestibility of dry matter from day 22 to 35, ileal Lactobacillus spp., villus height (duodenum and jejunum), and fewer coliforms (ileum) and Clostridium spp. (ileum). In Experiment 2, 200 weaned piglets were randomly allotted to four treatments. Dietary treatments included basal diet, basal diet supplemented with 3.0 g/kg fermented probiotic product (P), 1.0 g/kg bacteriophage cocktail (B) and combination of 1.0 g/kg bacteriophage cocktail and 3.0 g/kg fermented probiotic product. Pigs fed bacteriophage cocktail diets had greater (P<0.05) overall ADG, gain to feed ratio (G : F), fecal score from day 8 to day 21, and pigs fed bacteriophage cocktail diets had fewer coliforms (ileum) Clostridium spp. (ileum and cecum). Probiotics significantly increased G : F, colonization of Lactobacillus spp. in ileum. At day 35, bacteriophage treatment group showed greater (P<0.05) villus height of the duodenum, but a deeper crypt in duodenum. The present results indicate that the bacteriophage cocktail had a potential to enhance the performance and gut health of weanling pigs, however their combination with probiotics did not show an interaction. PMID- 27353335 TI - Stimulation map for control of functional grasp based on multi-channel EMG recordings. AB - Transcutaneous activation of muscles with electrical stimulation has limited selectivity in recruiting paralyzed muscles in stroke patients. However, the selectivity could be increased by the application of smaller electrodes and their appropriate positioning on the skin. We developed a method for selecting the appropriate positions of the stimulating electrodes based on electromyography (EMG). The EMG activity maps were estimated from signals recorded with two electrode arrays and two 24-channel wearable amplifiers positioned on the nonparetic and paretic forearms. The areas where the difference between the EMG maps obtained from the nonparetic and paretic arms was significant were identified as the stimulation sites. The stimulation was applied through array electrodes with magnetic holders and two wearable stimulators with four output channels each. The measures of functionality included joint angles measured with goniometers (hand opening) and grasp force measured with a multi-contact dynamometer (grasping). The stimulation protocol comprised co-activation of flexors and extensors to stabilize the wrist joint and prevent pronation/supination. PMID- 27353336 TI - The role of dendritic cells in male reproductive tract. AB - Dendritic cells (DCs) are the most potent professional antigen-presenting cells. The central role of various DC subsets as bridges between innate and adaptive immunity has become more and more evident. However, the role of DC subsets in male reproductive tract remains largely unexplored, in particular distinct DC subsets (including myeloid and plasmacytoid DCs), their maturation stage, and tissue distribution, as well as state of health or disease. Furthermore, infection and inflammation of male genital tract are thought to be a primary etiological factor of male infertility. This review sheds some light on this complex and rapidly growing field. It summarized the recent findings and deals with the characterization and role of DCs in male reproductive tract, that is, testis, epididymis, prostate, seminal vesicle, semen, and foreskin, which might help to understand the immunopathological mechanisms of male infertility and design effective vaccines for male reproductive health. PMID- 27353337 TI - Multifunction Sr, Co and F co-doped microporous coating on titanium of antibacterial, angiogenic and osteogenic activities. AB - Advanced multifunction titanium (Ti) based bone implant with antibacterial, angiogenic and osteogenic activities is stringently needed in clinic, which may be accomplished via incorporation of proper inorganic bioactive elements. In this work, microporous TiO2/calcium-phosphate coating on Ti doped with strontium, cobalt and fluorine (SCF-TiCP) was developed, which had a hierarchical micro/nano structure with a microporous structure evenly covered with nano-grains. SCF-TiCP greatly inhibited the colonization and growth of both gram-positive and gram negative bacteria. No cytotoxicity appeared for SCF-TiCP. Furthermore, SCF-TiCP stimulated the expression of key angiogenic factors in rat bone marrow stem cells (MSCs) and dramatically enhanced MSC osteogenic differentiation. The in vivo animal test displayed that SCF-TiCP induced more new bone and tighter implant/bone bonding. In conclusion, multifunction SCF-TiCP of antibacterial, angiogenic and osteogenic activities is a promising orthopedic and dental Ti implant coating for improved clinical performance. PMID- 27353338 TI - Toxicities and effects of insecticidal toxic baits to control Drosophila suzukii and Zaprionus indianus (Diptera: Drosophilidae). AB - BACKGROUND: Drosophila suzukii is a primary insect pest that causes direct damage to fruits with a thin epidermis such as strawberries, cherries and blueberries. In strawberry fields, the co-occurrence of D. suzukii and Zaprionus indianus has increased production losses. This study evaluated the toxicities and effects of insecticidal baits to control adults and larvae of both D. suzukii and Z. indianus. RESULTS: Organophosphate (dimethoate and malathion), spinosyn (spinosad and spinetoram), pyrethroid (lambda-cyhalothrin) and diamide (cyantraniliprole) insecticides exhibited high toxicity to both adults and larvae of D. suzukii and Z. indianus (mortality >80%) in topical and dip bioassays. However, when the insecticides were mixed with a feeding attractant, a positive effect was observed only for adults of D. suzukii. Insecticides containing neonicotinoids (acetamiprid and thiamethoxam) and pyrolle (chlorfenapyr) caused intermediate mortality to adults of D. suzukii (40-60%) and low mortality for Z. indianus (mortality <23%); however, these compounds reduced the larval infestation of the two species by 55-86%. Botanical (azadirachtin) and sulphur insecticides exhibited low toxicity (mortality <40%) on adults and larvae of both species. CONCLUSION: Dimethoate, malathion, spinosad, spinetoram, lambda-cyhalothrin and cyantraniliprole are highly toxic to both larvae and adults of D. suzukii and Z. indianus. The use of toxic baits for adults of D. suzukii could be an alternative in management of this species. (c) 2016 Society of Chemical Industry. PMID- 27353339 TI - Salusin-beta contributes to vascular inflammation associated with pulmonary arterial hypertension in rats. AB - OBJECTIVE: Inflammation is closely linked to pulmonary arterial hypertension (PAH). Salusin-beta, a bioactive peptide, has been reported to participate in vascular inflammation. We therefore hypothesized that salusin-beta contributes to monocrotaline (MCT)-induced PAH in rats. METHODS: Male Sprague-Dawley rats were treated with MCT (60 mg kg(-1), single intraperitoneal injection). Salusin-beta expression in the lungs of the MCT-treated rats was evaluated using immunofluorescence staining, western blot, and real-time PCR. For salusin-beta blockade assay, rats injected with MCT were given a chronic infusion of anti salusin-beta immunoglobulin G (IgG) (salusin-beta blocker, 1.0 MUg kg(-1) h(-1)) or isotype-matched control IgG. Four weeks after MCT+anti-salusin-beta treatment, the effects of salusin-beta blockade were determined using hemodynamics, western blot, real-time PCR, and immunohistochemical detection. The effect of salusin beta on human pulmonary arterial endothelial cell (HPAEC) function was detected by adhesion and tube formation experiments in vitro. RESULTS: Salusin-beta expression was significantly increased in the lungs of the MCT-treated rats, and immunofluorescence results showed that salusin-beta was predominantly expressed in pulmonary macrophages and vascular endothelial cells. Salusin-beta blockade significantly ameliorated PAH by acting against pulmonary vascular remodeling, decreasing macrophage infiltration, and reducing pro-inflammatory cytokine expression and nuclear factor-kappa B (NF-kappaB) activity in the lungs of the MCT-treated rats. In addition, salusin-beta could induce cell adhesion and accelerate angiogenesis by activating the NF-kappaB pathway and promoting pro inflammatory cytokine expression in the cultured HPAECs. This effect was suppressed by addition of the NF-kappaB inhibitor, N-acetyl-L-cysteine. CONCLUSIONS: Salusin-beta plays a crucial role in the development of MCT-induced PAH models. PMID- 27353340 TI - Involvement of Oct4 in the pathogenesis of thoracic aortic dissection via inducing the dedifferentiated phenotype of human aortic smooth muscle cells by directly upregulating KLF5. AB - OBJECTIVE: To investigate the expression of Oct4 in human thoracic aortic dissection (TAD) and the regulation mechanisms of Oct4 on phenotype transition of human aortic smooth muscle cells (HASMCs). METHODS: Aortic samples from TAD patients (n = 12) and organ donors (n = 6) were collected. qRT-PCR, western blot, and immunohistochemistry were performed to identify Oct4 expression in aortic media. Immunofluorescence was performed to analyze Oct4 expression in primary HASMCs. Oct4A and Oct4B isoforms were detected. Gain-of-function experiments were performed to determine the effects of Oct4 on HASMC phenotype transition. Chromatin immunoprecipitation, luciferase assay, and rescue experiments were performed to analyze mechanisms of Oct4 on HASMC phenotype transition. RESULTS: Oct4 expression levels, especially the Oct4A isoform, were significantly higher in TAD patients compared with normal controls. Notably, Oct4 presented a strong and strict nuclear localization in primary HASMCs of TAD patients but a mild and diffuse distribution in both cytoplasm and nucleus in the control group. Overexpression of Oct4 induced dedifferentiation of HASMCs characterized by decreased contractile proteins and elevated migration capability. Kruppel-like factor 5 (KLF5) was found to be a directly regulated target gene of Oct4 in HASMCs. Furthermore, downregulation of KLF5 significantly alleviated the effects of Oct4 on phenotype transition of HASMCs. CONCLUSIONS: Oct4 expression was significantly upregulated in aortic tissues and primary HASMCs of TAD patients. The increased Oct4 induced phenotype transition of HASMCs from the contractile type to the synthetic type by directly upregulating KLF5. PMID- 27353341 TI - Drug repurposing for chronic myeloid leukemia: in silico and in vitro investigation of DrugBank database for allosteric Bcr-Abl inhibitors. AB - Chronic myeloid leukemia (CML) is caused by chromosomal rearrangement resulting in the expression of Bcr-Abl fusion protein with deregulated Abl tyrosine kinase activity. Approved drugs - imatinib, dasatinib, nilotinib, and ponatinib - target the ATP-binding site of Abl kinase. Even though these drugs are initially effective, long-term usefulness is limited by the development of resistance. To overcome this problem, targeting the allosteric site of Abl kinase, which is remote from the ATP-binding site is found to be a useful strategy. In this study, structure-based and ligand-based virtual screening methods were applied to narrow down possible drugs (from DrugBank database) that could target the allosteric site of Abl kinase. Detailed investigations of the selected drugs in the allosteric site of Abl kinase, using molecular dynamics and steered molecular dynamics simulation shows that gefitinib, an EGFR inhibitor approved for the treatment of lung cancer, could bind effectively to the allosteric site of Bcr Abl. More interestingly, gefitinib was found to enhance the ability of imatinib to bind at the ATP-binding site of Bcr-Abl kinase. Based on the in silico findings, gefitinib was tested in combination with imatinib in K562 CML cell line using MTT cell proliferation assay and found to have a synergistic antiproliferative activity. Further detailed mechanistic study could help to unravel the full potential of imatinib - gefitinib combination for the treatment of CML. PMID- 27353342 TI - Facile synthesis of complex shaped Pt-Cu alloy architectures. AB - Several intricate Pt-Cu alloy architectures have been synthesized including hexapod backbones with stretchers and caved octahedron like hexapods, as well as some other intermediates with complex structures. The mechanistic study indicates that the shape is realized via a competitive effect between etching and growth induced by different chemicals. PMID- 27353343 TI - Tsunami-generated magnetic fields may constrain focal mechanisms of earthquakes. AB - A geomagnetic observatory named SFEMS is being operated on the deep seafloor in the northwest Pacific since August, 2001. SFEMS is capable of measuring both scalar and vector geomagnetic fields as well as the seafloor instrument's precise attitudes, which makes it a powerful tool in detecting the so-called oceanic dynamo effect. It was found that SFEMS captured clear magnetic signals generated by the giant tsunamis of the 2011 Tohoku Earthquake even for an epicentral distance of larger than 1500 km. Here we report estimates of the focal mechanism of a closer tsunamigenic earthquake in January, 2007 on the seaward slope of the Kuril Trench using tsunami-generated variations in the observed downward magnetic component. Three-dimensional solutions of the tsunami-generated magnetic components were calculated by a new numerical code based on non-uniform thin sheet approximation and particle motions of seawater using the linear Boussinesq approximation. As a result, a southeast dipping fault alone reproduced the dispersive nature of the downward magnetic component, while any northwest dipping faults could not. This implies that the tsunami-generated electromagnetic fields are useful for determination of focal mechanisms of tsunamigenic earthquakes, since fault dips are one of the most difficult source parameters to estimate even in modern seismology. PMID- 27353344 TI - Iminoguanidines as Allosteric Inhibitors of the Iron-Regulated Heme Oxygenase (HemO) of Pseudomonas aeruginosa. AB - New therapeutic targets are required to combat multidrug resistant infections, such as the iron-regulated heme oxygenase (HemO) of Pseudomonas aeruginosa, due to links between iron and virulence and dependence on heme as an iron source during infection. Herein we report the synthesis and activity of a series of iminoguanidine-based inhibitors of HemO. Compound 23 showed a binding affinity of 5.7 MUM and an MIC50 of 52.3 MUg/mL against P. aeruginosa PAO1. An in cellulo activity assay was developed by coupling HemO activity to a biliverdin-IXalpha dependent infrared fluorescent protein, in which compound 23 showed an EC50 of 11.3 MUM. The compounds showed increased activity against clinical isolates of P. aeruginosa, further confirming the target pathway. This class of inhibitors acts by binding to an allosteric site; the novel binding site is proposed in silico and supported by saturation transfer difference (STD) NMR as well as by hydrogen exchange mass spectrometry (HXMS). PMID- 27353346 TI - Three-dimensional microscopic analysis of clinical prostate specimens. AB - AIMS: Microscopic evaluation of prostate specimens for both clinical and research purposes is generally performed on 5-MUm-thick tissue sections. Because cross sections give a two-dimensional (2D) representation, little is known about the actual underlying three-dimensional (3D) architectural features of benign prostate tissue and prostate cancer (PCa). The aim of this study was to show that a combination of tissue-clearing protocols and confocal microscopy can successfully be applied to investigate the 3D architecture of human prostate tissue. METHODS AND RESULTS: Optical clearing of intact fresh and formalin-fixed paraffin-embedded (FFPE) clinical prostate specimens allowed us to visualize tissue structures up to a depth of 800 MUm, whereas, in uncleared tissue, detection of fluorescence was only possible up to 70 MUm. Fluorescent labelling with a general nuclear dye and antibodies against cytokeratin (CK) 5 and CK8-18 resulted in comprehensive 3D imaging of benign peripheral and transition prostate zones, as well as individual PCa growth patterns. After staining, clearing, and imaging, samples could still be processed for 2D (immuno)histochemical staining and DNA analysis, enabling additional molecular and diagnostic characterization of small tissue specimens. CONCLUSIONS: In conclusion, the applicability of 3D imaging to archival FFPE and fresh clinical specimens offers unlimited opportunities to study clinical and biological topics of interest in their actual 3D context. PMID- 27353345 TI - Site-specific covalent modifications of human insulin by catechol estrogens: Reactivity and induced structural and functional changes. AB - Proteins, covalently modified by catechol estrogens (CEs), were identified recently from the blood serum of diabetic patients and referred to as estrogenized proteins. Estrogenization of circulating insulin may occur and affect its molecular functioning. Here, the chemical reactivity of CEs towards specific amino acid residues of proteins and the structural and functional changes induced by the estrogenization of insulin were studied using cyclic voltammetry, liquid chromatography-mass spectrometry, circular dichroism spectroscopy, molecular modeling, and bioassays. Our results indicate that CEs, namely, 2- and 4-hydroxyl estrogens, were thermodynamically and kinetically more reactive than the catechol moiety. Upon co-incubation, intact insulin formed a substantial number of adducts with one or multiple CEs via covalent conjugation at its Cys 7 in the A or B chain, as well as at His10 or Lys29 in the B chain. Such conjugation was coupled with the cleavage of inter-chain disulfide linkages. Estrogenization on these sites may block the receptor-binding pockets of insulin. Insulin signaling and glucose uptake levels were lower in MCF-7 cells treated with modified insulin than in cells treated with native insulin. Taken together, our findings demonstrate that insulin molecules are susceptible to active estrogenization, and that such modification may alter the action of insulin. PMID- 27353348 TI - A Validated HPLC Method for the Determination of Linagliptin in Rat Plasma. Application to a Pharmacokinetic Study. AB - A sensitive and reproducible HPLC method for the determination of linagliptin (LNG) in rat plasma was developed and validated using pindolol (PIN) as the internal standard. Both LNG and PIN were separated on a Zorbax Eclipse XDB C18 column kept at ambient temperature using as mobile phase a combination of 75% methanol: 25% formic acid 0.1% pH 4.1 at a flow rate of 1.0 mL min-1 UV detection was performed at 254 nm. The method was validated in compliance with ICH guidelines and found to be linear in the range of 5-1,000 ng mL-1 The limit of quantification (LOQ) was found to be 5 ng mL-1 based on 100 uL of plasma. The variations for intra- and inter-assay precision were <10%, and the accuracy values were ranged between 93.3 and 102.5%. The extraction recovery (R%) was >83%. The assay was successfully applied to an in vivo pharmacokinetic study of LNG in rats that were administered a single oral dose of 10 mg kg-1 LNG. The maximum concentration (Cmax) and the area under the plasma concentration-time curve (AUC0-72) were 927.5 +/- 23.9 and 18,285.02 +/- 605.76 ng mL-1, respectively. PMID- 27353347 TI - Development of a spherically focused phased array transducer for ultrasonic image guided hyperthermia. AB - A 1.5 MHz prolate spheroidal therapeutic array with 128 circular elements was designed to accommodate standard imaging arrays for ultrasonic image-guided hyperthermia. The implementation of this dual-array system integrates real-time therapeutic and imaging functions with a single ultrasound system (Vantage 256, Verasonics). To facilitate applications involving small animal imaging and therapy the array was designed to have a beam depth of field smaller than 3.5 mm and to electronically steer over distances greater than 1 cm in both the axial and lateral directions. In order to achieve the required f number of 0.69, 1-3 piezocomposite modules were mated within the transducer housing. The performance of the prototype array was experimentally evaluated with excellent agreement with numerical simulation. A focal volume (2.70 mm (axial) * 0.65 mm (transverse) * 0.35 mm (transverse)) defined by the -6 dB focal intensity was obtained to address the dimensions needed for small animal therapy. An electronic beam steering range defined by the -3 dB focal peak intensity (17 mm (axial) * 14 mm (transverse) * 12 mm (transverse)) and -8 dB lateral grating lobes (24 mm (axial) * 18 mm (transverse) * 16 mm (transverse)) was achieved. The combined testing of imaging and therapeutic functions confirmed well-controlled local heating generation and imaging in a tissue mimicking phantom. This dual-array implementation offers a practical means to achieve hyperthermia and ablation in small animal models and can be incorporated within protocols for ultrasound mediated drug delivery. PMID- 27353349 TI - Development and Multi-laboratory Verification of US EPA Method 543 for the Analysis of Drinking Water Contaminants by Online Solid Phase Extraction-LC-MS MS. AB - A drinking water method for seven pesticides and pesticide degradates is presented that addresses the occurrence monitoring needs of the US Environmental Protection Agency (EPA) for a future Unregulated Contaminant Monitoring Regulation (UCMR). The method employs online solid phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS-MS). Online SPE-LC-MS-MS has the potential to offer cost-effective, faster, more sensitive and more rugged methods than the traditional offline SPE approach due to complete automation of the SPE process, as well as seamless integration with the LC-MS-MS system. The method uses 2-chloroacetamide, ascorbic acid and Trizma to preserve the drinking water samples for up to 28 days. The mean recoveries in drinking water (from a surface water source) fortified with method analytes are 87.1-112% with relative standard deviations of <14%. Single laboratory lowest concentration minimum reporting levels of 0.27-1.7 ng/L are demonstrated with this methodology. Multi laboratory data are presented that demonstrate method ruggedness and transferability. The final method meets all of the EPA's UCMR survey requirements for sample collection and storage, precision, accuracy, and sensitivity. PMID- 27353350 TI - HIV Drug Resistance in Antiretroviral-Naive Patients in Mexico After 10 Years: Is There a Difference? AB - The aim of this study was to compare the extent of resistance to antiretroviral (ARV) drugs among the population in Mexico before and after 2005. The mutations and drug resistance database of Stanford University were used for analyzing drug resistance tests that had been performed on HIV treatment-naive patients. The sequences obtained were divided into group 1 (isolated in 2002-2003) and group 2 (isolated in 2010-2014). Both groups showed 14% similarity in resistance mutations. In both groups, mutations in N88D protease inhibitor were identified, D67N and T69D were found for nucleoside reverse transcriptase inhibitors (NRTIs), and K103N was found for non-nucleoside reverse transcriptase inhibitors. In both groups, the resistance to ARV drugs was 7.4%. Both groups showed resistance to nelfinavir, efavirenz, and nevirapine. The prevalence of resistance to ARV therapy remained stable from 2002 to 2014. However, a marked reduction in resistance to NRTIs was observed for the same period. PMID- 27353351 TI - The erosion of nursing in Dutch mental health care: a critique on the proliferation of psychologists. PMID- 27353352 TI - Masked hypertension and allograft function in pediatric and young adults kidney transplant recipients. AB - Masked hypertension is a common complication of pediatric kidney transplantation. While office hypertension is known to be associated with worse short- and long term graft function, the role of masked hypertension in allograft dysfunction is not clear. We conducted a retrospective cross-sectional analysis of 77 consecutive pediatric kidney transplant recipients who had routine 24-h ambulatory blood pressure monitoring with the aims to estimate the prevalence of masked hypertension and examine its association with allograft function. Masked hypertension was defined as a 24-h systolic or diastolic blood pressure load >=25%. Twenty-nine percent of patients had masked hypertension. Patients with masked hypertension had significantly lower allograft function estimated using the creatinine-based Schwartz-Lyon formula, a cystatin C-based formula, and combined cystatin C and creatinine-based formulas than patients with normal blood pressure (all p values <0.05). In a multivariable analysis, masked hypertension remained independently associated with worse allograft function after adjustment for age, sex, race, time post-transplant, rejection history, antihypertensive treatment, and hemoglobin level. We conclude that in young kidney transplant recipients, masked hypertension is common and is associated with worse allograft function. These results support the case for routine ambulatory blood pressure monitoring as the standard of care in these patients to detect and treat masked hypertension. PMID- 27353353 TI - Quantitative projection of human brain penetration of the H3 antagonist PF 03654746 by integrating rat-derived brain partitioning and PET receptor occupancy. AB - 1. Unbound brain drug concentration (Cb,u), a valid surrogate of interstitial fluid drug concentration (CISF), cannot be directly determined in humans, which limits accurately defining the human Cb,u:Cp,u of investigational molecules. 2. For the H3R antagonist (1R,3R)-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1 lmethyl)phenyl]cyclobutane-1-carboxamide (PF-03654746), we interrogated Cb,u:Cp,u in humans and nonhuman primate (NHP). 3. In rat, PF-03654746 achieved net blood brain barrier (BBB) equilibrium (Cb,u:Cp,u of 2.11). 4. In NHP and humans, the PET receptor occupancy-based Cp,u IC50 of PF-03654746 was 0.99 nM and 0.31 nM, respectively, which were 2.1- and 7.4-fold lower than its in vitro human H3 Ki (2.3 nM). 5. In an attempt to understand this higher-than-expected potency in humans and NHP, rat-derived Cb,u:Cp,u of PF-03654746 was integrated with Cp,u IC50 to identify unbound (neuro) potency of PF-03654746, nIC50. 6. The nIC50 of PF-03654746 was 2.1 nM in NHP and 0.66 nM in human which better correlated (1.1- and 3.49-fold lower) with in vitro human H3 Ki (2.3 nM). 7. This correlation of the nIC50 and in vitro hH3 Ki suggested the translation of net BBB equilibrium of PF-03654746 from rat to NHP and humans, and confirmed the use of Cp,u as a reliable surrogate of Cb,u. 8. Thus, nIC50 quantitatively informed the human Cb,u:Cp,u of PF-03654746. PMID- 27353355 TI - Immune response to recombinant Leishmania infantum lipophosphoglycan 3 plus CpG oligodeoxynucleotides in BALB/c mice. AB - Development of a protective antileishmanial vaccine is an urgent priority for successful control of different forms of leishmaniasis. The potential of a recombinant lipophosphoglycan 3 (rLPG3) expressed by Leishmania tarentolae was evaluated in combination with CpG oligodeoxynucleotides (CpG-ODN) as a Th1 promoting adjuvant against Leishmania infantum infection in BALB/c mice. First, mice were immunized subcutaneously with rLPG3 either alone or in combination with CpG-ODN. Next, the immunogenic and protective efficacies of this vaccine were analysed in immunized mice. It was observed that coadministration of rLPG3 with CpG-ODN led to enhance in a Th1 response to rLPG3 induced by itself as the IFN gamma production was promoted in association with the predominant presence of IgG2a antibodies in the sera. However, immunization with rLPG3 plus CpG-ODN induced partial protection against infectious challenge in BALB/c mice. Taken together, further studies are required to improve the protective efficacy using either more potent immune enhancers or vaccination strategies. PMID- 27353354 TI - Transcriptome profiling of the rat retina after optic nerve transection. AB - Glaucoma is a group of eye diseases characterized by alterations in the contour of the optic nerve head (ONH), with corresponding visual field defects and progressive loss of retinal ganglion cells (RGCs). This progressive RGC death is considered to originate in axonal injury caused by compression of the axon bundles in the ONH. However, the molecular pathomechanisms of axonal injury induced RGC death are not yet well understood. Here, we used RNA sequencing (RNA seq) to examine transcriptome changes in rat retinas 2 days after optic nerve transection (ONT), and then used computational techniques to predict the resulting alterations in the transcriptional regulatory network. RNA-seq revealed 267 differentially expressed genes after ONT, 218 of which were annotated and 49 unannotated. We also identified differentially expressed transcripts, including potentially novel isoforms. An in silico pathway analysis predicted that CREB1 was the most significant upstream regulator. Thus, this study identified genes and pathways that may be involved in the pathomechanisms of axonal injury. We believe that our data should serve as a valuable resource to understand the molecular processes that define axonal injury-driven RGC death and to discover novel therapeutic targets for glaucoma. PMID- 27353356 TI - Antimicrobial activity of prodigiosin is attributable to plasma-membrane damage. AB - The bacterial pigment prodigiosin has various biological activities; it is, for instance, an effective antimicrobial. Here, we investigate the primary site targeted by prodigiosin, using the cells of microbial pathogens of humans as model systems: Candida albicans, Escherichia coli, Staphylococcus aureus. Inhibitory concentrations of prodigiosin; leakage of intracellular K+ ions, amino acids, proteins and sugars; impacts on activities of proteases, catalases and oxidases; and changes in surface appearance of pathogen cells were determined. Prodigiosin was highly inhibitory (30% growth rate reduction of C. albicans, E. coli, S. aureus at 0.3, 100 and 0.18 MUg ml-1, respectively); caused leakage of intracellular substances (most severe in S. aureus); was highly inhibitory to each enzyme; and caused changes to S. aureus indicative of cell-surface damage. Collectively, these findings suggest that prodigiosin, log Poctanol-water 5.16, is not a toxin but is a hydrophobic stressor able to disrupt the plasma membrane via a chaotropicity-mediated mode-of-action. PMID- 27353358 TI - Balloon angioplasty versus Viabahn stent graft for treatment of failing or thrombosed prosthetic hemodialysis grafts. AB - OBJECTIVE: To compare the results of stent graft placement to balloon angioplasty for the treatment of stenosis at the venous anastomosis of failing and thrombosed prosthetic hemodialysis grafts. METHODS: This prospective, multicenter trial included 293 patients randomized (1:1) to the stent graft (n = 145) or balloon angioplasty (n = 148) group for treatment of stenosis at the venous anastomosis of dysfunctional (n = 164) or thrombosed (n = 129) hemodialysis grafts. The primary study end point was target lesion primary patency at 6 months; participants were followed for up to 24 months. Primary patency of the access circuit was a secondary end point. Statistical analysis of effectiveness was performed using both the intent-to-treat population and the effectiveness-per protocol (EPP) populations for primary patency end points. Statistical analysis of additional effectiveness end points was performed using the EPP population. RESULTS: The 6-month target lesion primary patency was statistically greater in the stent graft group than the balloon angioplasty group (intent-to-treat, 51.6% vs 34.2% [P = .006]; EPP, 52.9% vs 35.5% [P = .008]). Compared with the angioplasty group, the stent graft group increased the median time from the index procedure to the next intervention on the target lesion by 95 days (203 vs 108 days). Patients with dysfunctional (stenotic) grafts had higher target lesion primary patency compared with patients with thrombosed grafts regardless of treatment (EPP, stent graft, 64.6% vs 36.1% and balloon angioplasty, 45.8% vs 23.5%). When compared with angioplasty, using a stent graft for treatment of a venous anastomotic stenosis of a thrombosed graft increased the 6-month target lesion primary patency by 53.6% (EPP, 36.1% vs 23.5%). CONCLUSIONS: When compared with balloon angioplasty, a stent graft provided superior target lesion primary patency at 6 months for treatment of venous anastomotic stenoses of dysfunctional and thrombosed prosthetic hemodialysis grafts. PMID- 27353359 TI - Autonomic outcome is better after endarterectomy than after stenting in patients with asymptomatic carotid stenosis. AB - OBJECTIVE: Carotid endarterectomy and stenting have comparable efficacy in stroke prevention in asymptomatic carotid stenosis. In patients with carotid stenosis, cardiac events have a more than threefold higher incidence than cerebrovascular events. Autonomic dysfunction predicts cardiovascular morbidity and mortality, and carotid stenosis interferes with baroreceptor and chemoreceptor function. We assessed the effect of elective carotid revascularization (endarterectomy vs stenting) on autonomic function as a major prognostic factor of cardiovascular health. METHODS: In 42 patients with >=70% asymptomatic extracranial carotid stenosis, autonomic function was determined by analysis of heart rate variability (total band power [TP], high frequency band power [HF], low-frequency band power [LF], very low frequency band power [VLF]), baroreflex sensitivity (alphaHF, alphaLF), respiratory chemoreflex sensitivity (central apnea-hypopnea index), and cardiac chemoreflex sensitivity (hyperoxic TP, HF, LF, and VLF ratios) before and 30 days after revascularization. RESULTS: Patients with endarterectomy were older than patients with stenting (69 +/- 7 vs 62 +/- 7 years; P <= .008) but did not differ in gender distribution and preintervention autonomic function. Compared with stenting, postintervention heart rate variability was higher (ln TP, 6.7 [95% confidence interval (CI), 6.3-7.0] vs 6.1 [95% CI, 5.8-6.5; P <= .009]; ln HF, 4.5 [95% CI, 4.1-5.0] vs 4.0 [95% CI, 3.4-4.5; P <= .05]; ln VLF, 6.0 [95% CI, 5.7-6.4] vs 5.5 [95% CI, 5.2-5.9; P <= .02]); respiratory chemoreflex sensitivity (central apnea-hypopnea index, 5.5 [95% CI, 2.8-8.2] vs 10.0 [95% CI, 6.9-13.1; P <=. 01]) and cardiac chemoreflex sensitivity (TP ratio, 1.2 [95% CI, 1.1-1.3] vs 1.0 [95% CI, 0.9-1.0; P <= .0001]; HF ratio, 1.4 [95% CI, 1.2-1.5] vs 0.9 [95% CI, 0.8-1.1; P <= .001]; LF ratio, 1.5 [95% CI, 1.3-1.6] vs 1.0 [95% CI, 0.8-1.1; P <= .0001]; VLF ratio, 1.2 [95% CI, 1.1-1.3) vs 1.0 [95% CI, 0.9-1.1; P <= .002]) were lower after endarterectomy. Postintervention baroreflex sensitivity did not differ after endarterectomy and stenting. CONCLUSIONS: Autonomic function was better after endarterectomy than after stenting. Better autonomic function after endarterectomy was based on restoration of chemoreceptor but not baroreceptor function and may improve cardiovascular long-term outcome. PMID- 27353357 TI - Pseudomonas aeruginosa in premise plumbing of large buildings. AB - Pseudomonas aeruginosa is an opportunistic bacterial pathogen that is widely occurring in the environment and is recognized for its capacity to form or join biofilms. The present review consolidates current knowledge on P. aeruginosa ecology and its implication in healthcare facilities premise plumbing. The adaptability of P. aeruginosa and its capacity to integrate the biofilm from the faucet and the drain highlight the role premise plumbing devices can play in promoting growth and persistence. A meta-analysis of P. aeruginosa prevalence in faucets (manual and electronic) and drains reveals the large variation in device positivity reported and suggest the high variability in the sampling approach and context as the main reason for this variation. The effects of the operating conditions that prevail within water distribution systems (disinfection, temperature, and hydraulic regime) on the persistence of P. aeruginosa are summarized. As a result from the review, recommendations for proactive control measures of water contamination by P. aeruginosa are presented. A better understanding of the ecology of P. aeruginosa and key influencing factors in premise plumbing are essential to identify culprit areas and implement effective control measures. PMID- 27353361 TI - Conservation and Diversification of the SHR-SCR-SCL23 Regulatory Network in the Development of the Functional Endodermis in Arabidopsis Shoots. AB - Development of the functional endodermis of Arabidopsis thaliana roots is controlled, in part, by GRAS transcription factors, namely SHORT-ROOT (SHR), SCARECROW (SCR), and SCARECROW-LIKE 23 (SCL23). Recently, it has been shown that the SHR-SCR-SCL23 regulatory module is also essential for specification of the endodermis (known as the bundle sheath) in leaves. Nevertheless, compared with what is known about the role of the SHR-SCR-SCL23 regulatory network in roots, the molecular interactions of SHR, SCR, and SCL23 are much less understood in shoots. Here, we show that SHR forms protein complexes with SCL23 to regulate transcription of SCL23 in shoots, similar to the regulation mode of SCR expression. Our results indicate that SHR acts as master regulator to directly activate the expression of SCR and SCL23. In the SHR-SCR-SCL23 network, we found a previously uncharacterized negative feedback loop whereby SCL23 modulates SHR levels. Through molecular, genetic, physiological, and morphological analyses, we also reveal that the SHR-SCR-SCL23 module plays a key role in the formation of the endodermis (known as the starch sheath) in hypocotyls. Taken together, our results provide new insights into the regulatory role of the SHR-SCR-SCL23 network in the endodermis development in both roots and shoots. PMID- 27353360 TI - The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding. AB - Heat shock protein-90 (Hsp90) is an essential molecular chaperone in eukaryotes involved in maintaining the stability and activity of numerous signalling proteins, also known as clients. Hsp90 ATPase activity is essential for its chaperone function and it is regulated by co-chaperones. Here we show that the tumour suppressor FLCN is an Hsp90 client protein and its binding partners FNIP1/FNIP2 function as co-chaperones. FNIPs decelerate the chaperone cycle, facilitating FLCN interaction with Hsp90, consequently ensuring FLCN stability. FNIPs compete with the activating co-chaperone Aha1 for binding to Hsp90, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins. Lastly, downregulation of FNIPs desensitizes cancer cells to Hsp90 inhibitors, whereas FNIPs overexpression in renal tumours compared with adjacent normal tissues correlates with enhanced binding of Hsp90 to its inhibitors. Our findings suggest that FNIPs expression can potentially serve as a predictive indicator of tumour response to Hsp90 inhibitors. PMID- 27353362 TI - PTOX Mediates Novel Pathways of Electron Transport in Etioplasts of Arabidopsis. AB - The immutans (im) variegation mutant of Arabidopsis defines the gene for PTOX (plastid terminal oxidase), a versatile plastoquinol oxidase in chloroplast membranes. In this report we used im to gain insight into the function of PTOX in etioplasts of dark-grown seedlings. We discovered that PTOX helps control the redox state of the plastoquinone (PQ) pool in these organelles, and that it plays an essential role in etioplast metabolism by participating in the desaturation reactions of carotenogenesis and in one or more redox pathways mediated by PGR5 (PROTON GRADIENT REGULATION 5) and NDH (NAD(P)H dehydrogenase), both of which are central players in cyclic electron transport. We propose that these elements couple PTOX with electron flow from NAD(P)H to oxygen, and by analogy to chlororespiration (in chloroplasts) and chromorespiration (in chromoplasts), we suggest that they define a respiratory process in etioplasts that we have termed "etiorespiration". We further show that the redox state of the PQ pool in etioplasts might control chlorophyll biosynthesis, perhaps by participating in mechanisms of retrograde (plastid-to-nucleus) signaling that coordinate biosynthetic and photoprotective activities required to poise the etioplast for light development. We conclude that PTOX is an important component of metabolism and redox sensing in etioplasts. PMID- 27353363 TI - Tumor microenvironment on the move and the Aselli connection. AB - The tumor microenvironment is involved in many activities that promote tumor cell growth, local spreading, and metastasis. In this issue of Science Signaling, Jung et al found that lymphangiogenesis may result from the cooperation of two molecules, sphingosine-1-phosphate (S1P) and lipocalin 2 (LCN2), produced by tumor cells and macrophages, respectively. The new S1P-LCN2 axis stresses the importance of innate immunity in remodeling the tumor microenvironment and in lymphangiogenesis. PMID- 27353364 TI - Lipocalin 2 from macrophages stimulated by tumor cell-derived sphingosine 1 phosphate promotes lymphangiogenesis and tumor metastasis. AB - Tumor cell-derived factors skew macrophages toward a tumor-supporting phenotype associated with the secretion of protumorigenic mediators. Apoptosing tumor cells release sphingosine 1-phosphate (S1P), which stimulates the production of lipocalin 2 (LCN2) in tumor-associated macrophages and is associated with tumor metastasis. We explored the mechanism by which S1P induces LCN2 in macrophages and investigated how this contributed to tumor growth and metastasis. Knockdown of S1P receptor 1 (S1PR1) in primary human macrophages and experiments with bone marrow-derived macrophages from S1PR1-deficient mice showed that S1P signaled through S1PR1 to induce LCN2 expression. The LCN2 promoter contains a consensus sequence for signal transducer and activator of transcription 3 (STAT3), and deletion of the STAT3 recognition sequence reduced expression of an LCN2 controlled reporter gene. Conditioned medium from coculture experiments indicated that the release of LCN2 from macrophages induced tube formation and proliferation in cultures of primary human lymphatic endothelial cells in a manner dependent on the kinase PI3K and subsequent induction of the growth factor VEGFC, which functioned as an autocrine signal stimulating the receptor VEGFR3. Knockout of Lcn2 attenuated tumor-associated lymphangiogenesis and breast tumor metastasis both in the breast cancer model MMTV-PyMT mice and in mice bearing orthotopic wild-type tumors. Our findings indicate that macrophages respond to dying tumor cells by producing signals that promote lymphangiogenesis, which enables metastasis. PMID- 27353366 TI - The adaptor protein CIN85 assembles intracellular signaling clusters for B cell activation. AB - The adaptor molecule Cbl-interacting protein of 85 kD (CIN85) regulates signaling from a number of cell surface receptors, such as growth factor receptors and antigen receptors on lymphocytes. Because of its multidomain structure, CIN85 is thought to act as a classical adaptor protein that connects functionally distinct components of a given signaling pathway through diverse protein domains. However, we found that in B lymphocytes, CIN85 functions to oligomerize SLP-65, which is the central effector protein of the B cell receptor (BCR). Therefore, CIN85 trimerizes through a carboxyl-terminal, coiled-coil domain. The multiple Src homology 3 (SH3) domains of trimeric CIN85 molecules associated with multiple SLP 65 molecules, which recruited further CIN85 trimers, thereby perpetuating the oligomerization process. Formation of this oligomeric signaling complex in resting B cells rendered the cells poised for the efficient initiation of intracellular signaling upon BCR stimulation. Our data suggest that the functionality of signaling cascades does not rely solely on the qualitative linkage of their various components but requires a critical number of effectors to become concentrated in signaling complexes. PMID- 27353365 TI - The ER structural protein Rtn4A stabilizes and enhances signaling through the receptor tyrosine kinase ErbB3. AB - ErbB3 and ErbB4 are receptor tyrosine kinases that are activated by the neuregulin (NRG) family of growth factors. These receptors govern various developmental processes, and their dysregulation contributes to several human disease states. The abundance of ErbB3 and ErbB4, and thus signaling through these receptors, is limited by the E3 ubiquitin ligase Nrdp1, which targets ErbB3 and ErbB4 for degradation. Reticulons are proteins that influence the morphology of the endoplasmic reticulum (ER) by promoting the formation of tubules, a response of cells to some stressors. We found that the ER structural protein reticulon 4A (Rtn4A, also known as Nogo-A) increased ErbB3 abundance and proliferative signaling by suppressing Nrdp1 function. Rtn4A interacted with Nrdp1 and stabilized ErbB3 in an Nrdp1-dependent manner. Rtn4A overexpression induced the redistribution of Nrdp1 from a cytosolic or perinuclear localization to ER tubules. Rtn4A knockdown in human breast tumor cells decreased ErbB3 abundance, NRG-stimulated signaling, and cellular proliferation and migration. Because proteins destined for the plasma membrane are primarily synthesized in the sheet portions of the ER, our observations suggest that Rtn4A counteracts the Nrdp1-mediated degradation of ErbB3 by sequestering the ubiquitin ligase into ER tubules. The involvement of a reticulon suggests a molecular link between ER structure and the sensitivity of cells to receptor tyrosine kinase-mediated survival signals at the cell surface. PMID- 27353367 TI - The efficacy of eye movement desensitization and reprocessing for post-traumatic stress disorder and depression among Syrian refugees: results of a randomized controlled trial. AB - BACKGROUND: Previous research indicates a high prevalence of post-traumatic stress disorder (PTSD) and depression among refugees. Eye movement desensitization and reprocessing (EMDR) is an effective treatment for PTSD for victims of natural disasters, car accidents or other traumatic events. The current study examined the effect of EMDR on symptoms of PTSD and depression by comparing the treatment with a wait-list control condition in Syrian refugees. METHOD: Adult refugees located in Kilis Refugee Camp at the Turkish-Syrian border with a PTSD diagnosis were randomly allocated to either EMDR (n = 37) or wait list control (n = 33) conditions. All participants were assessed with the Mini International Neuropsychiatric Interview Plus at pre-intervention, at 1 week after finishing the intervention and at 5 weeks after finishing the intervention. The main outcome measures were the Harvard Trauma Questionnaire (HTQ) and the Impact of Event Scale-Revised. The Beck Depression Inventory and the Hopkins Symptoms Checklist-25 were included as secondary outcome measures. The Trial Registration no. is NCT01847742. RESULTS: Mixed-model analyses adjusted for the baseline scores indicated a significant effect of group at post-treatment indicating that the EMDR therapy group showed a significantly larger reduction of PTSD symptoms as assessed with the HTQ. Similar findings were found on the other outcome measures. There was no effect of time or group * time interaction on any measure, showing that the difference between the groups at the post-treatment was maintained to the 5-week follow-up. CONCLUSIONS: EMDR may be effective in reducing PTSD and depression symptoms among Syrian refugees with PTSD located in a refugee camp. PMID- 27353368 TI - Long-Term Palliative Effect of Stenting in Gastric Outlet Obstruction Due to Transarterial Chemoembolization with Yttrium-90 in a Patient with Metastatic Neuroendocrine Tumor. AB - Internal radioembolization with yttrium-90 is a promising treatment method, predominantly for liver tumors. However, the shifting of yttrium-90-loaded spherules into the arteries and veins that supply the duodenum and stomach, leading to ulceration, hemorrhage, perforation, and outlet obstruction of these organs, is one of the major undesirable consequences of this technique. We report a case of gastric outlet obstruction (GOO) due to antropyloric stenosis with ulceration, edema, and inflammation following transarterial yttrium-90 treatment for a metastatic neuroendocrine tumor in a 58-year-old man. Stenting was used for palliation in this case. GOO improved after stenting and recovery of oral intake was permanent after stent removal. PMID- 27353370 TI - Photocatalytic degradation of carbofuran by TiO2-coated activated carbon: Model for kinetic, electrical energy per order and economic analysis. AB - The photocatalytic removal of carbofuran (CBF) from aqueous solution in the presence of granular activated carbon supported TiO2 (GAC-TiO2) catalyst was investigated under batch-mode experiments. The presence of GAC enhanced the photocatalytic efficiency of the TiO2 catalyst. Experiments were conducted at different concentrations of CBF to clarify the dependence of apparent rate constant (kapp) in the pseudo first-order kinetics on CBF photodegradation. The general relationship between the adsorption equilibrium constant (K) and reaction rate constant (kr) were explained by using the modified Langmuir-Hinshelwood (L H) model. From the observed kinetics, it was observed that the surface reaction was the rate limiting step in the GAC-TiO2 catalyzed photodegradation of CBF. The values of K and kr for this pseudo first-order reaction were found to be 0.1942 L mg(-1) and 1.51 mg L(-1) min(-1), respectively. In addition, the dependence of kapp on the half-life time was determined by calculating the electrical energy per order experimentally (EEO experimental) and also by modeling (EEO model). The batch-mode experimental outcomes revealed the possibility of 100% CBF removal (under optimized conditions and at an initial concentration of 50 mg L(-1) and 100 mg L(-1)) at a contact time of 90 min and 120 min, respectively. Both L-H kinetic model and EEO model fitted well with the batch-mode experimental data and also elucidated successfully the phenomena of photocatalytic degradation in the presence of GAC-TiO2 catalyst. PMID- 27353369 TI - Evaluation of Faecalibacterium 16S rDNA genetic markers for accurate identification of swine faecal waste by quantitative PCR. AB - A genetic marker within the 16S rRNA gene of Faecalibacterium was identified for use in a quantitative PCR (qPCR) assay to detect swine faecal contamination in water. A total of 146,038 bacterial sequences were obtained using 454 pyrosequencing. By comparative bioinformatics analysis of Faecalibacterium sequences with those of numerous swine and other animal species, swine-specific Faecalibacterium 16S rRNA gene sequences were identified and Polymerase Chain Okabe (PCR) primer sets designed and tested against faecal DNA samples from swine and non-swine sources. Two PCR primer sets, PFB-1 and PFB-2, showed the highest specificity to swine faecal waste and had no cross-reaction with other animal samples. PFB-1 and PFB-2 amplified 16S rRNA gene sequences from 50 samples of swine with positive ratios of 86 and 90%, respectively. We compared swine specific Faecalibacterium qPCR assays for the purpose of quantifying the newly identified markers. The quantification limits (LOQs) of PFB-1 and PFB-2 markers in environmental water were 6.5 and 2.9 copies per 100 ml, respectively. Of the swine-associated assays tested, PFB-2 was more sensitive in detecting the swine faecal waste and quantifying the microbial load. Furthermore, the microbial abundance and diversity of the microbiomes of swine and other animal faeces were estimated using operational taxonomic units (OTUs). The species specificity was demonstrated for the microbial populations present in various animal faeces. PMID- 27353371 TI - The drivers of wildfire enlargement do not exhibit scale thresholds in southeastern Australian forests. AB - Wildfires are complex adaptive systems, and have been hypothesized to exhibit scale-dependent transitions in the drivers of fire spread. Among other things, this makes the prediction of final fire size from conditions at the ignition difficult. We test this hypothesis by conducting a multi-scale statistical modelling of the factors determining whether fires reached 10 ha, then 100 ha then 1000 ha and the final size of fires >1000 ha. At each stage, the predictors were measures of weather, fuels, topography and fire suppression. The objectives were to identify differences among the models indicative of scale transitions, assess the accuracy of the multi-step method for predicting fire size (compared to predicting final size from initial conditions) and to quantify the importance of the predictors. The data were 1116 fires that occurred in the eucalypt forests of New South Wales between 1985 and 2010. The models were similar at the different scales, though there were subtle differences. For example, the presence of roads affected whether fires reached 10 ha but not larger scales. Weather was the most important predictor overall, though fuel load, topography and ease of suppression all showed effects. Overall, there was no evidence that fires have scale-dependent transitions in behaviour. The models had a predictive accuracy of 73%, 66%, 72% and 53% accuracy at 10 ha, 100 ha, 1000 ha and final size scales. When these steps were combined, the overall accuracy for predicting the size of fires was 62%, while the accuracy of the one step model was only 20%. Thus, the multi-scale approach was an improvement on the single scale approach, even though the predictive accuracy was probably insufficient for use as an operational tool. The analysis has also provided further evidence of the important role of weather, compared to fuel, suppression and topography in driving fire behaviour. PMID- 27353372 TI - Assessing effectiveness of WEEE management policy in Australia. AB - Australia is one of the top ten consumers of electrical and electronic (EE) products in the world; yet legislation for the management of WEEE (Waste Electrical and Electronic Equipment) is in its infancy and has received minimal review. This paper sets to assess the effectiveness of Australian legislation, policies and associated instruments, with a focus on the sub-national level of implementation. A mixed methodology was adopted to this end, including: literature review, case study, semi-structured interviews and a comparative analysis of WEEE management practices in Australia versus Japan and Switzerland; the latter to identify causative factors of international leading practice that could advance current policy in Australia. The findings indicate that Australia's management of WEEE is not effective. The rate and types of WEEE generated in Australia far exceed the measures prescribed in legislation to address or even curb the problem. The five key issues were identified around stakeholder roles and responsibilities; scope of WEEE categories legislated for recovery and recycling; public engagement and accessibility to services; recycling and material recovery targets; and the auditing and compliance of material flows within the system. Our findings suggest that Australia has the capacity to address the five key priority areas within the current legal framework and achieve effective WEEE management in line with leading practice examples from Japan and Switzerland. PMID- 27353373 TI - Biomimetic synthesis of selenium nanoparticles by Pseudomonas aeruginosa ATCC 27853: An approach for conversion of selenite. AB - A facile and green method for the reduction of selenite was developed using a Gram-negative bacterial strain Pseudomonas aeruginosa, under aerobic conditions. During the process of bacterial conversion, the elemental selenium nanoparticles were produced. These nanoparticles were systematically characterized using various analytical techniques including UV-visible spectroscopy, XRD, Raman spectroscopy, SEM, DLS, TEM and FTIR spectroscopy techniques. The generation of selenium nanoparticles was confirmed from the appearance of red colour in the culture broth and broad absorption peaks in the UV-vis. The synthesized nanoparticles were spherical, polydisperse, ranged from 47 to 165 nm and the average particle size was about 95.9 nm. The selected-area electron diffraction, XRD patterns; and Raman spectroscopy established the amorphous nature of the fabricated nanoparticles. The IR data demonstrated the bacterial protein mediated selenite reduction and capping of the produced nanoparticles. The selenium removal was assessed at different selenite concentrations using ICP-OES and the results showed that the tested bacterial strain exhibited significant selenite reduction activity. The results demonstrate the possible application of P. aeruginosa for bioremediation of waters polluted with toxic and soluble selenite. Moreover, the potential metal reduction capability of the bacterial strain can function as green method for aerobic generation of selenium nanospheres. PMID- 27353374 TI - Treatment of sugarcane vinasse by combination of coagulation/flocculation and Fenton's oxidation. AB - The efficiency of individual and integrated processes applied to organic matter reduction and biodegradability improvement of a biodigested sugarcane vinasse wastewater was assessed. Strategies considered were Fenton's oxidation (Strategy 1), coagulation/flocculation (Strategy 2) and the combination of both processes (coagulation/flocculation followed by Fenton's reaction) - Strategy 3. It was found that Fenton's oxidation per se allowed reducing the organic matter, increasing the wastewater biodegradability and a non-toxic effluent was generated; however the cost of treatment was very high (86.6 R$/m(3) - 21.2 ?/m(3)). Under optimized conditions, coagulation/flocculation provided a slight increase in effluent's biodegradability, toxicity towards Vibrio fischeri was also eliminated and moderate removals of total organic carbon - TOC - (30.5%), biological oxygen demand - BOD5 - (27.9%) and chemical oxygen demand - COD - (43.6%) were achieved; however, the operating costs are much smaller. The use of dissolved iron resulting from coagulation/flocculation (270 mg/L) as catalyst in the second stage - Fenton's oxidation - was shown to be an innovative and economically attractive strategy. Under optimal conditions overall removals of 51.6% for TOC, 45.7% for BOD5 and 69.2% for COD were achieved, and a biodegradable (BOD5:COD ratio = 0.54) and non-toxic effluent was obtained. In order to increase the efficiency of the process but using less hydrogen peroxide, the Fenton's oxidation was performed by gradually adding the oxidant. This procedure allowed to obtain the highest organic matter removal efficiency (as compared with the addition of all hydrogen peroxide at the beginning of the reaction). This way it was possible to minimize the reagent consumption and, consequently, reduce the treatment cost. PMID- 27353375 TI - Coherent destruction of tunneling in two-level system driven across avoided crossing via photon statistics. AB - In this paper, the nature of the multi-order resonance and coherent destruction of tunneling (CDT) for two-level system driven cross avoided crossing is investigated by employing the emitted photons and the Mandel's Q parameter based on the photon counting statistics. An asymmetric feature of CDT is shown in the spectrum of Mandel's Q parameter. Also, the CDT can be employed to suppress the spontaneous decay and prolong waiting time noticeably. The photon emission pattern is of monotonicity in strong relaxation, and homogeneity in pure dephasing regime, respectively. PMID- 27353376 TI - A ratiometric two-photon fluorescent probe for fluoride ion imaging in living cells and zebrafish. AB - Using 6-hydroxyl-quinoline-2-benzothiazole (HQB) as a two-photon fluorophore and tert-butyldiphenylsilyl as a recognition domain for F(-), a ratiometric two photon fluorescent fluoride probe, QF, was synthesized and fully characterized. QF displays both one- and two-photon ratiometric responses towards fluoride ions in aqueous solution. QF was enabled to detect exogenous fluoride ions in living cells by a ratiometric method. Two-photon microscopic imaging of fluoride ions in living HeLa cells and zebrafish has also been achieved. QF has been demonstrated to be an excellent fluorescent probe with high selectivity, low cytotoxicity and good photostability. PMID- 27353377 TI - ZNF70, a novel ILDR2-interacting protein, contributes to the regulation of HES1 gene expression. AB - A diabetes susceptibility gene, immunoglobulin-like domain containing receptor 2 (Ildr2), encodes a transmembrane protein localized to the endoplasmic reticulum membrane that is closely related to hepatic lipid metabolism. The livers of ob/ob mice in which Ildr2 is transiently overexpressed are relieved of hepatic steatosis. However, the molecular mechanisms through which ILDR2 affects these changes in hepatic lipid metabolism remain unknown. This study aimed to identify ILDR2-interacting proteins to further elucidate the molecular mechanisms underlying the role of ILDR2 in lipid homeostasis. We purified ILDR2-containing protein complexes using tandem affinity purification tagging and identified ZNF70, a member of the Kruppel C2H2-type zinc finger protein family, as a novel ILDR2-interacting protein. We demonstrated that ZNF70 interacts with ZFP64 and activates HES1 transcription by binding to the HES1 promoter. In addition, HES1 gene expression is increased in ILDR2-knockdown HepG2 cells, in which ZNF70 is translocated from the cytoplasm to the nucleus, suggesting that ZNF70 migration to the nucleus after dissociating from the ILDR2-ZNF70 complex activates HES1 transcription. These results support a novel link between ILDR2 and HES1 gene expression and suggest that ILDR2 is involved in a novel pathway in hepatic steatosis. PMID- 27353378 TI - Crystal structures of human peroxiredoxin 6 in different oxidation states. AB - Peroxiredoxins (Prxs) are a family of antioxidant enzymes found ubiquitously. Prxs function not only as H2O2 scavengers but also as highly sensitive H2O2 sensors and signal transducers. Since reactive oxygen species are involved in many cellular metabolic and signaling processes, Prxs play important roles in various diseases. Prxs can be hyperoxidized to the sulfinic acid (SO2H) or sulfonic acid (SO3H) forms in the presence of high concentrations of H2O2. It is known that oligomerization of Prx is changed accompanying oxidation states, and linked to the function. Among the six Prxs in mammals, Prx6 is the only 1-Cys Prx. It is found in all organs in humans, unlike some 2-Cys Prxs, and is present in all species from bacteria to humans. In addition, Prx6 has Ca(2+)-independent phospholipase A2 (PLA2) activity. Thus far only the crystal structure of Prx in the oxidized state has been reported. In this study, we present the crystal structures of human Prx6 in the reduced (SH) and the sulfinic acid (SO2H) forms. PMID- 27353379 TI - The lysine biosynthetic enzyme Lys4 influences iron metabolism, mitochondrial function and virulence in Cryptococcus neoformans. AB - The lysine biosynthesis pathway via alpha-aminoadipate in fungi is considered an attractive target for antifungal drugs due to its absence in mammalian hosts. The iron-sulfur cluster-containing enzyme homoaconitase converts homocitrate to homoisocitrate in the lysine biosynthetic pathway, and is encoded by LYS4 in the model yeast Saccharomyces cerevisiae. In this study, we identified the ortholog of LYS4 in the human fungal pathogen, Cryptococcus neoformans, and found that LYS4 expression is regulated by iron levels and by the iron-related transcription factors Hap3 and HapX. Deletion of the LYS4 gene resulted in lysine auxotrophy suggesting that Lys4 is essential for lysine biosynthesis. Our study also revealed that lysine uptake was mediated by two amino acid permeases, Aap2 and Aap3, and influenced by nitrogen catabolite repression (NCR). Furthermore, the lys4 mutant showed increased sensitivity to oxidative stress, agents that challenge cell wall/membrane integrity, and azole antifungal drugs. We showed that these phenotypes were due in part to impaired mitochondrial function as a result of LYS4 deletion, which we propose disrupts iron homeostasis in the organelle. The combination of defects are consistent with our observation that the lys4 mutant was attenuated virulence in a mouse inhalation model of cryptococcosis. PMID- 27353380 TI - Differential effects of two-pore channel protein 1 and 2 silencing in MDA-MB-468 breast cancer cells. AB - Two-pore channel proteins, TPC1 and TPC2, are calcium permeable ion channels found localized to the membranes of endolysosomal calcium stores. There is increasing interest in the role of TPC-mediated intracellular signaling in various pathologies; however their role in breast cancer has not been extensively evaluated. TPC1 and TPC2 mRNA was present in all non-tumorigenic and tumorigenic breast cell lines assessed. Silencing of TPC2 but not TPC1 attenuated epidermal growth factor-induced vimentin expression in MDA-MB-468 breast cancer cells. This effect was not due to a general inhibition of epithelial to mesenchymal transition (EMT) as TPC2 silencing had no effect on epidermal growth factor (EGF) induced changes on E-cadherin expression. TPC1 and TPC2 were also shown to differentially regulate cyclopiazonic acid (CPA)-mediated changes in cytosolic free Ca(2+). These findings indicate potential differential regulation of signaling processes by TPC1 and TPC2 in breast cancer cells. PMID- 27353381 TI - Macrothrombocytopenia With Dohle Body-Like Granulocyte Inclusions: A Case Report of May-Hegglin Anomaly in a 33-Year-Old White Woman With an Update on the Molecular Findings of MYH9-Related Disease. AB - A 33-year-old white woman arrived at the hospital to undergo a hysterectomy due to uterine fibroids. Blood smear review identified macrothrombocytopenia and Dohle body-like cytoplasmic leukocyte inclusions. Genetic testing identified a mutation in exon 39 of the myosin heavy chain gene (MHY9; OMIM 160775), which confirmed the diagnosis of May-Hegglin anomaly. May-Hegglin anomaly is one of a spectrum of MYH9 disorders that also includes Sebastian, Epstein, and Fechtner syndromes. Herein, we describe the clinical and laboratory presentation of a patient with May-Hegglin anomaly and provide an update on the molecular findings and a discussion of the genotypic-phenotypic correlations in this potentially underdiagnosed disorder. PMID- 27353382 TI - Nitrous Oxide Production in Co- Versus Counter-Diffusion Nitrifying Biofilms. AB - For the application of biofilm processes, a better understanding of nitrous oxide (N2O) formation within the biofilm is essential for design and operation of biofilm reactors with minimized N2O emissions. In this work, a previously established N2O model incorporating both ammonia oxidizing bacteria (AOB) denitrification and hydroxylamine (NH2OH) oxidation pathways is applied in two structurally different biofilm systems to assess the effects of co- and counter diffusion on N2O production. It is demonstrated that the diffusion of NH2OH and oxygen within both types of biofilms would form an anoxic layer with the presence of NH2OH and nitrite ( ), which would result in a high N2O production via AOB denitrification pathway. As a result, AOB denitrification pathway is dominant over NH2OH oxidation pathway within the co- and counter-diffusion biofilms. In comparison, the co-diffusion biofilm may generate substantially higher N2O than the counter-diffusion biofilm due to the higher accumulation of NH2OH in co diffusion biofilm, especially under the condition of high-strength ammonium influent (500 mg N/L), thick biofilm depth (300 MUm) and moderate oxygen loading (~1-~4 m(3)/d). The effect of co- and counter-diffusion on N2O production from the AOB biofilm is minimal when treating low-strength nitrogenous wastewater. PMID- 27353383 TI - Positive Lymph Node Ratio as an Indicator of Prognosis and Local Tumor Clearance in N3 Gastric Cancer. AB - BACKGROUND: Nodal metastasis is an important clinical issue in gastric cancer patients. This study was designed to investigate the clinical usefulness of the positive lymph node ratio (PLNR), which reflects both metastatic and retrieved lymph node numbers, in patients with pN3 gastric cancer. METHODS: We retrospectively analyzed the records of 138 consecutive pN3 patients who underwent curative gastrectomy with lymphadenectomy from 2000 to 2012. RESULTS: A PLNR of 0.4 was proved to be the best cutoff value to stratify the prognosis of patients with pN3 gastric cancer (P < 0.001). Univariate and multivariate analyses revealed that older age, larger tumor size (>=10 cm), and PLNR >= 0.4 [P < 0.001, HR 3.1 (95 % CI 1.7-5.4)] were independent prognostic factors in pN3 gastric cancer. Regarding the recurrence, patients with PLNR <0.4 had a significantly lower rate of lymph node recurrence than those with PLNR >=0.4 (P = 0.020). There was no significant difference in the lymph node recurrence rate between N3a and N3b patients in the PLNR <0.4 group [P = 0.546, 11.6 % (7/60) vs. 12.5 (1/8)], indicating a better local control regardless of pN3 subgroups. CONCLUSIONS: PLNR is useful to stratify the prognosis and evaluate the extent of local tumor clearance in pN3 gastric cancer. PMID- 27353384 TI - Unplanned reattendances at the paediatric emergency department within 72 hours: a one-year experience in KKH. AB - INTRODUCTION: Unscheduled reattendances at the paediatric emergency department may contribute to overcrowding, which may increase financial burdens. The objectives of this study were to determine the rate of reattendances and characterise factors influencing these reattendances and hospital admission during the return visits. METHODS: Medical records of all patients who attended the emergency department at KK Women's and Children's Hospital, Singapore, from 1 June 2013 to 31 May 2014 were retrospectively reviewed. We collected data on patient demographics, attendance data and clinical characteristics. Planned reattendances, recalled cases, reattendances for unrelated complaints and patients who left without being seen were excluded. A multivariate analysis was conducted to determine the odds ratio of variables associated with hospital admission for reattendances. RESULTS: Of 162,566 children, 6,968 (4.3%) returned within 72 hours, and 2,925 (42.0% of reattendance group) were admitted on their return visits. Children more likely to reattend were under three years of age, Chinese, triaged as Priority 2 at the first visit, and were initially diagnosed with respiratory or gastrointestinal conditions. However, children more likely to be admitted on their return visits were over 12 years of age, Malay, had a higher triage acuity or were uptriaged, had the presence of a comorbidity, and were diagnosed with gastrointestinal conditions. CONCLUSION: We identified certain subgroups in the population who were more likely to be admitted if they reattended. These findings would help in implementing further research and directing strategies to reduce potentially avoidable reattendances and admissions. PMID- 27353385 TI - School-based interventions for improving contraceptive use in adolescents. AB - BACKGROUND: Young women, especially adolescents, often lack access to modern contraception. Reasons vary by geography and regional politics and culture. The projected 2015 birth rate in 'developing' regions was 56 per 1000 compared with 17 per 1000 for 'developed' regions. OBJECTIVES: To identify school-based interventions that improved contraceptive use among adolescents SEARCH METHODS: Until 6 June 2016, we searched for eligible trials in PubMed, CENTRAL, ERIC, Web of Science, POPLINE, ClinicalTrials.gov and ICTRP. SELECTION CRITERIA: We considered randomized controlled trials (RCTs) that assigned individuals or clusters. The majority of participants must have been 19 years old or younger.The educational strategy must have occurred primarily in a middle school or high school. The intervention had to emphasize one or more effective methods of contraception. Our primary outcomes were pregnancy and contraceptive use. DATA COLLECTION AND ANALYSIS: We assessed titles and abstracts identified during the searches. One author extracted and entered the data into RevMan; a second author verified accuracy. We examined studies for methodological quality.For unadjusted dichotomous outcomes, we calculated the Mantel-Haenszel odds ratio (OR) with 95% confidence interval (CI). For cluster randomized trials, we used adjusted measures, e.g. OR, risk ratio, or difference in proportions. For continuous outcomes, we used the adjusted mean difference (MD) or other measures from the models. We did not conduct meta-analysis due to varied interventions and outcome measures. MAIN RESULTS: The 11 trials included 10 cluster RCTs and an individually randomized trial. The cluster RCTs had sample sizes from 816 to 10,954; the median number of clusters was 24. Most trials were conducted in the USA and UK; one was from Mexico and one from South Africa.We focus here on the trials with moderate quality evidence and an intervention effect. Three addressed preventing pregnancy and HIV/STI through interactive sessions. One trial provided a multifaceted two-year program. Immediately after year one and 12 months after year two, the intervention group was more likely than the standard-curriculum group to report using effective contraception during last sex (reported adjusted ORs 1.62 +/- standard error (SE) 0.22) and 1.76 +/- SE 0.29), condom use during last sex (reported adjusted ORs 1.91 +/- SE 0.27 and 1.68 +/- SE 0.25), and less frequent sex without a condom in the past three months (reported ratios of adjusted means 0.50 +/- SE 0.31 and 0.63 +/- SE 0.23). Another trial compared multifaceted two-year programs on sexual risk reduction and risk avoidance (abstinence-focused) versus usual health education. At 3 months, the risk reduction group was less likely than the usual-education group to report no condom use at last intercourse (reported adjusted OR 0.67, 95% CI 0.47 to 0.96) and sex without a condom in the last three months (reported adjusted OR 0.59, 95% CI 0.36 to 0.95). At 3 and after 15 months, the risk avoidance group was also less likely than the usual-education group to report no condom use at last intercourse (reported adjusted ORs 0.70, 95% CI 0.52 to 0.93; and 0.61, 95% CI 0.45 to 0.85). At the same time points, the risk reduction group had a higher score than the usual-education group for condom knowledge. The third trial provided a peer-led program with eight interactive sessions. At 17 months, the intervention group was less likely than the teacher-led group to report oral contraceptive use during last sex (OR 0.57, 95% CI 0.36 to 0.91). This difference may not have been significant if the investigators had adjusted for the clustering. At 5 and 17 months, the peer-led group had a greater mean increase in knowledge of HIV and pregnancy prevention compared with the control group. An additional trial showed an effect on knowledge only. The group with an emergency contraception (EC) session was more likely than the group without the EC unit to know the time limits for using hormonal EC (pill) and the non-hormonal IUD as EC. AUTHORS' CONCLUSIONS: Since most trials addressed preventing STI/HIV and pregnancy, they emphasized condom use. However, several studies covered a range of contraceptive methods. The overall quality of evidence was low. Main reasons for downgrading the evidence were having limited information on intervention fidelity, analyzing a subsample rather than all those randomized, and having high losses. PMID- 27353386 TI - Severity of gambling problems modulates autonomic reactions to near outcomes in gambling. AB - Outcomes in gambling games cannot only be classified based on their valence (wins and misses) but also based on their closeness (near and full outcomes). The present study investigated autonomic responses (phasic heart period changes and skin conductance responses) to near and full outcomes on a wheel of fortune in a sample of males with different degrees of gambling problems. Near relative to full outcomes elicited increased interbeat intervals shortly after outcome presentation. Furthermore, participants with more severe gambling problems showed increased skin conductance responses following near relative to full outcomes as well as relatively smaller interbeat interval responses to near relative to full misses. The findings confirm different processing of near compared to full outcomes and altered processing of gambling outcomes with increasing severity of gambling problems. PMID- 27353387 TI - Fertility Control: Reproductive Desires, Kin Work, and Women's Status in Contemporary India. AB - This article reappraises the link between fertility and women's status by examining changing means and meanings of reproduction in India. It is based on data gathered during and after 16 months of ethnographic fieldwork conducted between 2005 and 2007 in Lucknow, Uttar Pradesh, India, on social and cultural contexts of infertility. Lucknow is the capital city of Uttar Pradesh, India's most populous state. Historical views of population and fertility control in India and perspectives on the contemporary use of assisted reproductive technologies (ARTs) for practices such as surrogacy situate the ethnographic perspectives. Analysis of ARTs in practice complicates ideas of autonomy and choice in reproduction. Results show that these technologies allow women to challenge power relations within their marital families and pursue stigmatized forms of reproduction. However, they also offer new ways for families to continue and extend an old pattern of exerting control over women's reproductive potential. PMID- 27353388 TI - New light on bacterial carbonic anhydrases phylogeny based on the analysis of signal peptide sequences. AB - Among protein families, carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes characterized by a common reaction mechanism in all life domains: the carbon dioxide hydration to bicarbonate and protons (CO2+H2O <=> HCO3(-)+H(+)). Six genetically distinct CA families are known to date, the alpha-, beta-, gamma-, delta-, zeta- and eta-CAs. The last CA class was recently discovered analyzing the amino acid sequences of CAs from Plasmodia. Bacteria encode for enzymes belonging to the alpha-, beta-, and gamma-CA classes and recently, phylogenetic analysis revealed an interesting relationship regarding the evolution of bacterial CA classes. This result evidenced that the three bacterial CA classes, in spite of the high level of the structural similarity, are evolutionarily distinct, but we noted that the primary structure of some beta-CAs identified in the genome of Gram-negative bacteria present a pre-sequence of 18 or more amino acid residues at the N-terminal part. These observations and subsequent phylogenetic data presented here prompted us to propose that the beta-CAs found in Gram-negative bacteria with a periplasmic space and characterized by the presence of a signal peptide might have a periplasmic localization and a role similar to that described previously for the alpha-CAs. PMID- 27353389 TI - Transport of the outer dynein arm complex to cilia requires a cytoplasmic protein Lrrc6. AB - Lrrc6 encodes a cytoplasmic protein that is expressed specifically in cells with motile cilia including the node, trachea and testes of the mice. A mutation of Lrrc6 has been identified in human patients with primary ciliary dyskinesia (PCD). Mutant mice lacking Lrrc6 show typical PCD defects such as hydrocephalus and laterality defects. We found that in the absence of Lrrc6, the morphology of motile cilia remained normal, but their motility was completely lost. The 9 + 2 arrangement of microtubules remained normal in Lrrc6(-/-) mice, but the outer dynein arms (ODAs), the structures essential for the ciliary beating, were absent from the cilia. In the absence of Lrrc6, ODA proteins such as DNAH5, DNAH9 and IC2, which are assembled in the cytoplasm and transported to the ciliary axoneme, remained in the cytoplasm and were not transported to the ciliary axoneme. The IC2-IC1 interaction, which is the first step of ODA assembly, was normal in Lrrc6(-/-) mice testes. Our results suggest that ODA proteins may be transported from the cytoplasm to the cilia by an Lrrc6-dependent mechanism. PMID- 27353390 TI - The importance of the unit of analysis: Commentary on Beugels et al. (2016). Complications in unilateral versus bilateral deep inferior epigastric artery perforator flap breast reconstructions: A multicentre study. PMID- 27353391 TI - Gravity packaging final waste recovery based on gravity separation and chemical imaging control. AB - Plastic polymers are characterized by a high calorific value. Post-consumer plastic waste can be thus considered, in many cases, as a typical secondary solid fuels according to the European Commission directive on End of Waste (EoW). In Europe the practice of incineration is considered one of the solutions for waste disposal waste, for energy recovery and, as a consequence, for the reduction of waste sent to landfill. A full characterization of these products represents the first step to profitably and correctly utilize them. Several techniques have been investigated in this paper in order to separate and characterize post-consumer plastic packaging waste fulfilling the previous goals, that is: gravity separation (i.e. Reflux Classifier), FT-IR spectroscopy, NIR HyperSpectralImaging (HSI) based techniques and calorimetric test. The study demonstrated as the proposed separation technique and the HyperSpectral NIR Imaging approach allow to separate and recognize the different polymers (i.e. PolyVinyl Chloride (PVC), PolyStyrene (PS), PolyEthylene (PE), PoliEtilene Tereftalato (PET), PolyPropylene (PP)) in order to maximize the removal of the PVC fraction from plastic waste and to perform the full quality control of the resulting products, can be profitably utilized to set up analytical/control strategies finalized to obtain a low content of PVC in the final Solid Recovered Fuel (SRF), thus enhancing SRF quality, increasing its value and reducing the "final waste". PMID- 27353392 TI - A mathematical model for municipal solid waste management - A case study in Hong Kong. AB - With the booming economy and increasing population, the accumulation of waste has become an increasingly arduous issue and has aroused the attention from all sectors of society. Hong Kong which has a relative high daily per capita domestic waste generation rate in Asia has not yet established a comprehensive waste management system. This paper conducts a review of waste management approaches and models. Researchers highlight that mathematical models provide useful information for decision-makers to select appropriate choices and save cost. It is suggested to consider municipal solid waste management in a holistic view and improve the utilization of waste management infrastructures. A mathematical model which adopts integer linear programming and mixed integer programming has been developed for Hong Kong municipal solid waste management. A sensitivity analysis was carried out to simulate different scenarios which provide decision-makers important information for establishing Hong Kong waste management system. PMID- 27353393 TI - Evaluation of recycled concrete aggregates for their suitability in construction activities: An experimental study. AB - Construction and demolition waste disposal is a major challenge in developing nations due to its ever increasing quantities. In this study, the recycling potential of waste concrete as aggregates in construction activities was studied. The metal leaching from the recycled concrete aggregates (RCA) collected from the demolition site of a 50year old building, was evaluated by performing three different leaching tests (compliance, availability and Toxic Characteristic Leaching Procedure). The metal leaching was found mostly within the permissible limit except for Hg. Several tests were performed to determine the physical and mechanical properties of the fine and coarse aggregates produced from recycled concrete. The properties of recycled aggregates were found to be satisfactory for their utilization in road construction activities. The suitability of using recycled fine and coarse aggregates with Portland pozzolanic cement to make a sustainable and environmental friendly concrete mix design was also analyzed. No significant difference was observed in the compressive strength of various concrete mixes prepared by natural and recycled aggregates. However, only the tensile strength of the mix prepared with 25% recycled fine aggregates was comparable to that of the control concrete. For other mixes, the tensile strength of the concrete was found to drop significantly. In summary, RCA should be considered seriously as a building material for road construction, mass concrete works, lightly reinforced sections, etc. The present work will be useful for the waste managers and policy makers particularly in developing nations where proper guidelines are still lacking. PMID- 27353394 TI - Improvements of physical, mechanical and biodegradation properties of polybutadiene rubber insulators by chitosan and silica nanoparticles. AB - 1,4-cis-Polybutadiene rubber(1,4-cis pBR) as an insulation material is developing that will provide superior thermal insulation properties, flexibility, toughness by natural polymers such as chitosan(CS) and silica nanoparticles. This material is widely used in the insulation industries specially architecture. This research concerns physical, mechanical properties and also biodegradation of 1,4-cis pBR, which to be composed with the natural polymers such as CS. Silica nanoparticles were used as filler to improve the physical and mechanical properties of 1,4-cis pBR. To evaluating its physical and mechanical properties, stretching and bending and impact tests were used and the results show some improvement in these properties. Our observations show that temperature plays an important role as main factor in order to improve the mechanical properties of nanocomposites. Similar improvements in tensile modulus and strength have been observed for 1,4 cis pBR/CS-silica nanoparticles. PMID- 27353395 TI - Contemporary retroperitoneal lymph node dissection (RPLND) for testis cancer in the UK - a national study. AB - OBJECTIVES: To undertake a comprehensive prospective national study of the outcomes of retroperitoneal lymph node dissection (RPLND) for testis cancer over a 1-year period in the UK. PATIENTS AND METHODS: Data were submitted online using the British Association of Urological Surgeons Section of Oncology Data and Audit System. All new patients undergoing RPLND for testis cancer between March 2012 and February 2013 were studied prospectively. Data were analysed using Tableau software and case ascertainment compared with Hospital Episode Statistics data. RESULTS: In all, 162 men underwent RPLND by 20 surgeons in 17 centres. The mean (range) case volume per centre was 9 (2-32) and the median (range) case volume per surgeon was 6 (1-30). Indications included: residual mass after chemotherapy (73%), primary treatment (6%), relapse (14%), and salvage (7%). The median time to surgery after chemotherapy was 8-12 weeks (<4 - >12 weeks) and 91% of procedures utilised open surgery. The median operating time was 3-4 h (<1.5 - >6 h). Nerve sparing was performed in 67% of patients (19% bilateral, 48% unilateral). The dissection was template in 81% and lumpectomy in 16%; 25% required additional intraoperative procedures including 11% synchronous planned nephrectomy. In all, 157/160 (98%) of recorded RPLND operations were completed. One was terminated due to bleeding and in two the mass could not be removed. There were no deaths within 30 days of surgery. In all, 75% of the men did not require a blood transfusion, 15% required 1-2 units and 10% received >2 units. There were postoperative complications in 10% of the men (Clavien-Dindo Grade I, seven men; Grade II, seven; and Grade III, one). The mean (range) length of stay was 5.5 (1-59) days. Histology showed necrosis in 22%; teratoma differentiated in 42%; and residual cancer in 36%. CONCLUSIONS: This prospective collaborative national study describes for the first time the surgical outcomes after RPLND across the UK. The quality of RPLND in the UK appears high. The study can act as a benchmark for this type of surgery across the world. PMID- 27353396 TI - Epidemiology of Diabetes Mellitus among 193,435 Cats Attending Primary-Care Veterinary Practices in England. AB - BACKGROUND: Diabetes mellitus (DM) is a common endocrine disease of cats. The prevalence of DM in cats in England is not well-defined. HYPOTHESIS/OBJECTIVES: To estimate the prevalence and identify risk factors for DM in a large population of cats attending primary-care practices. ANIMALS: A cohort of 193,563 cats in the VetCompass Programme attending 118 primary-care practices in England. METHODS: Cross-sectional analysis of cohort clinical data. Data were extracted covering September 1st 2009 and August 31st 2014. Period prevalence of DM was calculated. Associations between risk factors and DM were assessed using logistic regression modelling. RESULTS: Of 1,128 DM cases were identified among 194,563 cats (period prevalence 0.58%; 95% confidence interval [CI] 0.54-0.61). Multivariable modelling indicated that Tonkinese (OR 4.1; 95% CI 1.8-9.6; P = .001), Norwegian Forest (odds ratio [OR] 3.5; 95% CI 1.3-9.6; P = .001) and Burmese (OR 3.0; 95% CI 2.0-4.4; P < .001) cats had increased odds of DM compared with crossbred cats. DM odds increased as bodyweight categories increased above 4 kg (P < .001), as cats aged beyond 6 years old (P < .001) and in insured cats (OR 2.0; 95% CI 1.6-2.4; P < .001) but sex was not significantly associated with DM. CONCLUSIONS AND CLINICAL IMPORTANCE: Diabetes mellitus is an important component of the primary-care practice caseload with 1-in-200 cats affected. An increased risk of DM in certain cat breeds supports a genetic predisposition. These results can guide future research and preventative healthcare. PMID- 27353397 TI - The genes that encode the gonococcal transferrin binding proteins, TbpB and TbpA, are differentially regulated by MisR under iron-replete and iron-depleted conditions. AB - Neisseria gonorrhoeae produces two transferrin binding proteins, TbpA and TbpB, which together enable efficient iron transport from human transferrin. We demonstrate that expression of the tbp genes is controlled by MisR, a response regulator in the two-component regulatory system that also includes the sensor kinase MisS. The tbp genes were up-regulated in the misR mutant under iron replete conditions but were conversely down-regulated in the misR mutant under iron-depleted conditions. The misR mutant was capable of transferrin-iron uptake at only 50% of wild-type levels, consistent with decreased tbp expression. We demonstrate that phosphorylated MisR specifically binds to the tbpBA promoter and that MisR interacts with five regions upstream of the tbpB start codon. These analyses confirm that MisR directly regulates tbpBA expression. The MisR binding sites in the gonococcus are only partially conserved in Neisseria meningitidis, which may explain why tbpBA was not MisR-regulated in previous studies using this related pathogen. This is the first report of a trans-acting protein factor other than Fur that can directly contribute to gonococcal tbpBA regulation. PMID- 27353398 TI - Indolent T- and NK-cell lymphoproliferative disorders of the gastrointestinal tract: a review and update. AB - Primary gastrointestinal (GI) T- and NK-cell lymphomas are usually aggressive neoplasms associated with high morbidity and mortality. Over the past two decades, however, cases of primary GI lymphoproliferative disorders (LPDs) or lymphomas of T- or NK-cell derivation with indolent behavior have been reported. These LPDs are rare and they can be challenging to diagnose as they share clinical and pathological features with both, inflammatory disorders and aggressive T- and NK-cell lymphomas. Primary, indolent clonal T-cell proliferations of the GI tract, which can be CD4+, CD8+ or CD4- CD8-, have been included as a provisional entity in the newly revised World Health Organization (WHO) classification of lymphoid neoplasms and designated 'indolent T-cell LPD of the GI tract'. It is currently unclear whether the indolent NK-cell LPDs represent reactive or neoplastic proliferations. In this review, we describe the clinical, morphologic, immunophenotypic and genetic features of indolent GI T- and NK-cell LPDs and provide guidance in differentiating them from other inflammatory and neoplastic diseases. We believe that greater awareness of these LPDs amongst physicians and the research community will lead to timely and accurate diagnoses, stimulate investigations into the pathogenetic mechanisms underlying different entities thereby enhancing our understanding of disease biology and enable the development of effective therapeutic regimens. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27353399 TI - Retraction notice to "Anti-fibrotic cardio protective efficacy of Aminoguanidine against Streptozotocin induced cardiac fibrosis and high glucose induced collagen up regulation in cardiac fibroblasts" [CBI 197 (2012) 119-128]. PMID- 27353400 TI - Nutrition: How will the next 'Decade of Nutrition' be different from the past one? PMID- 27353401 TI - Endoscopic mucosal resection and endoscopic submucosal dissection of large colonic polyps. AB - Almost all large and complex colorectal polyps can now be resected endoscopically. Piecemeal endoscopic mucosal resection (PEMR) is an established technique with fairly low complication risk and good short-term and medium-term outcomes. Several modifications to the basic injection and snare technique have been developed contributing to safer and more complete resections. Delayed bleeding requiring reintervention is the most troublesome complication in 2-7% of patients, particularly in those with comorbidities and large, right-sided polyps. Endoscopic submucosal dissection (ESD) has become popular in Japan and has theoretical advantages over PEMR in providing a complete, en bloc excision for accurate histological staging and reduced local recurrence. These advantages come at the cost of a more complex, expensive and time-consuming procedure with a higher risk of perforation, particularly early in the procedure learning curve. These factors have contributed to the slow adoption of ESD in the West and the challenge to develop new devices and endoscopic platforms that will make ESD easier and safer. Currently, ESD indications are limited to large rectal lesions, in which procedural complications are easily managed, and for colorectal polyps with a high risk of containing tiny foci of early submucosally invasive cancer, whereby ESD may be curative compared with PEMR. PMID- 27353402 TI - Liver regeneration - mechanisms and models to clinical application. AB - Liver regeneration has been studied for many decades and the mechanisms underlying regeneration of the normal liver following resection or moderate damage are well described. A large number of factors extrinsic (such as bile acids and circulating growth factors) and intrinsic to the liver interact to initiate and regulate liver regeneration. Less well understood, and more clinically relevant, are the factors at play when the abnormal liver is required to regenerate. Fatty liver disease, chronic scarring, prior chemotherapy and massive liver injury can all inhibit the normal programme of regeneration and can lead to liver failure. Understanding these mechanisms could enable the rational targeting of specific therapies to either reduce the factors inhibiting regeneration or directly stimulate liver regeneration. Although animal models of liver regeneration have been highly instructive, the clinical relevance of some models could be improved to bridge the gap between our in vivo model systems and the clinical situation. Likewise, modern imaging techniques such as spectroscopy will probably improve our understanding of whole-organ metabolism and how this predicts the liver's regenerative capacity. This Review describes briefly the mechanisms underpinning liver regeneration, the models used to study this process, and discusses areas in which failed or compromised liver regeneration is clinically relevant. PMID- 27353403 TI - Obesity: Metabolically healthy obesity and NAFLD. PMID- 27353405 TI - Time- and ensemble-averages in evolving systems: the case of Brownian particles in random potentials. AB - Anomalous diffusion is a ubiquitous phenomenon in complex systems. It is often quantified using time- and ensemble-averages to improve statistics, although time averages represent a non-local measure in time and hence can be difficult to interpret. We present a detailed analysis of the influence of time- and ensemble averages on dynamical quantities by investigating Brownian particles in a rough potential energy landscape (PEL). Initially, the particle ensemble is randomly distributed, but the occupancy of energy values evolves towards the equilibrium distribution. This relaxation manifests itself in the time evolution of time- and ensemble-averaged dynamical measures. We use Monte Carlo simulations to study particle dynamics in a potential with a Gaussian distribution of energy values, where the long-time limit of the diffusion coefficient is known from theory. In our experiments, individual colloidal particles are exposed to a laser speckle pattern inducing a non-Gaussian roughness and are followed by optical microscopy. The relaxation depends on the kind and degree of roughness of the PEL. It can be followed and quantified by the time- and ensemble-averaged mean squared displacement. Moreover, the heterogeneity of the dynamics is characterized using single-trajectory analysis. The results of this work are relevant for the correct interpretation of single-particle tracking experiments in general. PMID- 27353404 TI - Transitional care interventions and hospital readmissions in surgical populations: a systematic review. AB - BACKGROUND: Despite hospital readmission being a targeted quality metric, few studies have focused on the surgical patient population. We performed a systematic review of transitional care interventions and their effect on hospital readmissions after surgery. DATA SOURCES: PubMed was searched for studies evaluating transitional care interventions in surgical populations within the years 1995 to 2015. Of 3,527 abstracts identified, 3 randomized controlled trials and 7 observational cohort studies met inclusion criteria. CONCLUSIONS: Discharge planning programs reduced readmissions by 11.5% (P = .001), 12.5% (P = .04), and 23% (P = .26). Patient education interventions reduced readmissions by 14% (P = .28) and 23.5% (P < .05). Primary care follow-up reduced readmissions by 8.3% for patients after high-risk surgeries (P < .001). Home visits reduced readmissions by 7.69% (P = .023) and 4% (P = .161), respectively. Therefore, improving discharge planning, patient education, and follow-up communication may reduce readmissions. PMID- 27353406 TI - Functional and oncologic outcome of cemented endoprosthesis for malignant proximal femoral tumors. AB - BACKGROUND: Cemented endoprosthetic replacement is an option for reconstruction of the proximal femur to achieve limb salvage. Existing outcome studies combine benign and malignant conditions, or group endoprostheses from multiple areas into one cohort. We sought to examine a series of endoprosthetic replacements of the proximal femur for a malignant process. METHODS: We reviewed 204 patients who underwent an endoprosthesis for a malignant process of the proximal femur with at least 2-year follow-up. Mean age was 59 years, with 55% being male. The most common pathology was metastatic disease (n = 120, 59%). Mean follow-up was 7 years (2-22 years). Mean time to death was 2 years (range 2 weeks-18 years). A bipolar component was used in 93% of patients. RESULTS: 5-year survival was 8% in patients with metastatic disease and 54% for patients with primary disease. Local recurrence and metastatic disease developed in 5 and 19 patients with a primary sarcoma. Following the procedure the mean Harris Hip and Musculoskeletal Tumor Society Scores were 75 and 18. CONCLUSION: Patients typically succumb to their disease prior to implant failure; however, endoprosthetic replacement provides patients with an acceptable means of functional recovery with an acceptable complication profile. J. Surg. Oncol. 2016;114:501-506. (c) 2016 Wiley Periodicals, Inc. PMID- 27353407 TI - Normal fundal morphology obscuring a unicornuate and an equally developed blind uterine horn - an unclassified Mullerian variant. PMID- 27353409 TI - Therapeutic potential of targeting TBK1 in autoimmune diseases and interferonopathies. AB - The serine/threonine protein kinase, TBK1, plays a crucial role as the hub for many innate immune signaling pathways that lead to the induction of type I interferon (IFN) and interferon-stimulated genes (ISGs). Due to its key function in maintaining homeostasis of the immune system, cell survival and proliferation, TBK1 activity is tightly regulated. Dysregulation of TBK1 activity is often associated with autoimmune diseases and cancer, implicating the potential therapeutic benefit for targeting TBK1. Tremendous effort from both academic institutions and private sectors during the past few years has led to the development of many potent and selective TBK1 inhibitors, many of which have shown great promise in disease models in vivo. This review summarizes recent advance on the pharmacological inhibition of TBK1 and its potential for treating autoimmune diseases and interferonopathies. PMID- 27353410 TI - Social supports and mental health: a cross-sectional study on the correlation of self-consistency and congruence in China. AB - BACKGROUND: Psychosocial job characteristics require nursing staff with high self consistency and good mental health. However, the attention and effort of such study remained very limited in China. METHODS: A self-administered questionnaire was distributed to the bedside nurses in an affiliated hospital of Hebei Medical University, China. Of 218 registered bedside nurses eligible to participate in the survey anonymously, the data producing sample of 172 subjects resulted in a 79 % of effective response rate.. The Social Support Rating Scale was used to measure social support, and the Self-Consistency and Congruence Scale were used to measure mental health. RESULTS: Compared with the normal referenced group of college students, higher self-flexibility scores, lower self-conflict and self stethoscope scores from the sample group were obtained with statistical significance in self-conflict scores. The close correlations were observed between participants' social support and Self-Consistency and Congruence Scale score. The difference of Social Support Rating Scale score was significant in demographic features including years of work, marital status, only child family, and levels of cooperation with other health worker. CONCLUSIONS: Bedside nurses in this study show a better inner harmony, and their Self-Consistency and Congruence closely correlates with the levels of social support. Thus, it is substantial to improve inner perception of support and external factors, such as the workplace support, and offer beneficial social environment to improve the bedside nurse's sub-health symptoms and decrease the high turnover rate. PMID- 27353411 TI - Use of donated clotting factors for surgeries on haemophilic patients in a resource-constrained country: a kind donor, good outcome, change of practice and future directions. PMID- 27353412 TI - Facial nerve repair after operative injury: Impact of timing on hypoglossal facial nerve graft outcomes. AB - PURPOSE: Reanimation of facial paralysis is a complex problem with multiple treatment options. One option is hypoglossal-facial nerve grafting, which can be performed in the immediate postoperative period after nerve transection, or in a delayed setting after skull base surgery when the nerve is anatomically intact but function is poor. The purpose of this study is to investigate the effect of timing of hypoglossal-facial grafting on functional outcome. MATERIALS AND METHODS: A retrospective case series from a single tertiary otologic referral center was performed identifying 60 patients with facial nerve injury following cerebellopontine angle tumor extirpation. Patients underwent hypoglossal-facial nerve anastomosis following facial nerve injury. Facial nerve function was measured using the House-Brackmann facial nerve grading system at a median follow up interval of 18months. Multivariate logistic regression analysis was used determine how time to hypoglossal-facial nerve grafting affected odds of achieving House-Brackmann grade of <=3. RESULTS: Patients who underwent acute hypoglossal-facial anastomotic repair (0-14days from injury) were more likely to achieve House-Brackmann grade <=3 compared to those that had delayed repair (OR 4.97, 95% CI 1.5-16.9, p=0.01). CONCLUSIONS: Early hypoglossal-facial anastomotic repair after acute facial nerve injury is associated with better long-term facial function outcomes and should be considered in the management algorithm. PMID- 27353414 TI - A life-course and multifactorial approach to Alzheimer's disease: Implications for research, clinical assessment and intervention practices. AB - According to the dominant biomedical view, Alzheimer's disease (AD) has a precise, necessary and unifying neurobiological cause, which distinguishes it from other neurodegenerative diseases and normal ageing. However, different types of evidence specifically lead to questioning the foundations of this essentialist and category-based approach to AD. It seems more and more evident that AD represents a heterogeneous state, determined by multiple factors and mechanisms that interact and intervene throughout life. This other way of conceiving AD not only requires a change of research objectives, but also a profound modification of clinical assessment and intervention practices. It also appeals to follow the path of prevention. PMID- 27353413 TI - Risk of Venous Thromboembolism After Laparoscopic Surgery for Gynecologic Malignancy. AB - STUDY OBJECTIVE: To determine the incidence of venous thromboembolism (VTE) after laparoscopic surgery for gynecologic cancer. DESIGN: Retrospective analysis of the ACS-NSQIP database (Canadian Task Force Classification II.1). SETTING: Academic and community healthcare institutions across the United States. PATIENTS: Women who underwent at least 1 major laparoscopic surgery for uterine, ovarian, and cervical cancers. INTERVENTION: Data were collected on surgical procedures, patient demographic variables, type of malignancy and VTE, and mortality outcomes within 30 days of surgery. MEASUREMENTS AND MAIN RESULTS: VTE was defined as deep venous thrombosis requiring therapy and pulmonary embolism confirmed by imaging or autopsy within 30 days of surgery. Of the 2219 patients included in the final analysis, 15 patients (.7%) were diagnosed with VTE within 30 days after surgery. Six patients (.3%) were diagnosed before discharge, and 9 patients (.4%) were diagnosed after discharge. The median time from surgery to diagnosis was 6 days (range, 0-28 days). Although most patients included in the study had uterine cancer (86%, n = 1913), no difference was noted based on the site of cancer (.5% for cervical cancer, .7% for endometrial cancer, and .8% for ovarian cancer; p = .95). There was no difference in rate of VTE when stratified by age (p = .10), body mass index (p = .68), diabetes (p = .22), smoking (p = .60), respiratory morbidities (p = .55), cardiac disease (p = .22), hypertension (p = .13), preoperative blood transfusion (p = .90), or American Society of Anesthesiologists class (p = .10). There was a trend toward higher risk of VTE among patients with disseminated cancer compared with those with early cancers (3.6% vs .6%, p = .05). No difference was found in the risk of VTE based on operative time (.7% for <2 hours, .6% for 2-3 hours, and .7% for >3 hours; p = .96). No difference was noted in the risk of VTE among those who underwent lymphadenectomy compared with those who did not (.9% vs .5%, p = .35). In multivariable logistic regression analysis adjusting age (p = .12), body mass index (p = .90), operative time (p = .71), and lymphadenectomy (p = .30), none of these variables was significantly associated with risk of VTE. In multivariable analysis adjusting for other confounders, VTE within 30 days was a significant predictor of higher 30-day mortality (OR, 26.0; 95% CI, 2.2-306.9; p = .01). CONCLUSION: The rate of VTE is low after major laparoscopic surgery for gynecologic cancers but is associated with increased 30-day mortality. Universal or extended thromboprophylaxis does not appear to be indicated for all patients. Further studies are needed to identify patients at high risk for postoperative VTE who may benefit from pharmacologic prophylaxis. PMID- 27353415 TI - Bioinformatics analysis of differentially expressed pathways related to the metastatic characteristics of osteosarcoma. AB - In this study, gene expression data of osteosarcoma (OSA) were analyzed to identify metastasis-related biological pathways. Four gene expression data sets (GSE21257, GSE9508, GSE49003 and GSE66673) were downloaded from Gene Expression Omnibus (GEO). An analysis of differentially expressed genes (DEGs) was performed using the Significance Analysis of Microarray (SAM) method. Gene expression levels were converted into scores of pathways by the Functional Analysis of Individual Microarray Expression (FAIME) algorithm and the differentially expressed pathways (DEPs) were then disclosed by a t-test. The distinguishing and prediction ability of the DEPs for metastatic and non-metastatic OSA was further confirmed using the principal component analysis (PCA) method and 3 gene expression data sets (GSE9508, GSE49003 and GSE66673) based on the support vector machines (SVM) model. A total of 616 downregulated and 681 upregulated genes were identified in the data set, GSE21257. The DEGs could not be used to distinguish metastatic OSA from non-metastatic OSA, as shown by PCA. Thus, an analysis of DEPs was further performed, resulting in 14 DEPs, such as NRAS signaling, Toll like receptor (TLR) signaling, matrix metalloproteinase (MMP) regulation of cytokines and tumor necrosis factor receptor-associated factor (TRAF)-mediated interferon regulatory factor 7 (IRF7) activation. Cluster analysis indicated that these pathways could be used to distinguish between metastatic OSA from non metastatic OSA. The prediction accuracy was 91, 66.7 and 87.5% for the data sets, GSE9508, GSE49003 and GSE66673, respectively. The results of PCA further validated that the DEPs could be used to distinguish metastatic OSA from non metastatic OSA. On the whole, several DEPs were identified in metastatic OSA compared with non-metastatic OSA. Further studies on these pathways and relevant genes may help to enhance our understanding of the molecular mechanisms underlying metastasis and may thus aid in the development of novel therapies. PMID- 27353416 TI - Innominate Artery Stenosis Presenting With Migratory Digital Ischemia. AB - BACKGROUND: Atherosclerotic lesions of the supra-aortic trunk vessels, including the innominate artery, subclavian artery, or the common carotid artery, tend to present either as low-flow state distal to the lesion or as embolic events. The risk of embolic cerebrovascular event complicates the management of this condition via a pure endovascular approach. A combined operative-endovascular intervention may be a valuable approach in order to reduce the risk of intraoperative stroke and prevent future embolic events. CASE PRESENTATION: An 84 year-old female presented at the emergency department (ED) with a 4-month history of migratory digital cyanotic lesions across various fingers on her right hand. The lesion eventually progressed into dry gangrene on her right middle finger. Selective angiography of the aortic arch vessels demonstrated significant atherosclerotic plaque burden throughout her supra-aortic vessels and a segmental stenosis at the proximal innominate artery. A right carotid cut down was performed to allow clamping of the carotid artery so as to minimize the risk of intraoperative stroke from plaque manipulation. Retrograde balloon angioplasty was performed, and stent was placed across the stenotic segment. The patient tolerated the procedure well and had an uneventful postoperative course. She was discharged on postoperative day 3. At 2-week follow-up, she has had no progression of her digital ischemia nor other focal cranial nerve deficits. CONCLUSION: Migratory digital ischemia is a rare presentation of atherosclerotic disease of the supra-aortic vessels. It represents a challenging situation for endovascular intervention due to concern about plaque dislodgment during the procedure. A retrograde balloon-stent angioplasty following distal carotid control with an open approach may be safe and effective in selected patients. PMID- 27353417 TI - GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction. PMID- 27353419 TI - A new approach for categorizing pig lying behaviour based on a Delaunay triangulation method. AB - Machine vision-based monitoring of pig lying behaviour is a fast and non intrusive approach that could be used to improve animal health and welfare. Four pens with 22 pigs in each were selected at a commercial pig farm and monitored for 15 days using top view cameras. Three thermal categories were selected relative to room setpoint temperature. An image processing technique based on Delaunay triangulation (DT) was utilized. Different lying patterns (close, normal and far) were defined regarding the perimeter of each DT triangle and the percentages of each lying pattern were obtained in each thermal category. A method using a multilayer perceptron (MLP) neural network, to automatically classify group lying behaviour of pigs into three thermal categories, was developed and tested for its feasibility. The DT features (mean value of perimeters, maximum and minimum length of sides of triangles) were calculated as inputs for the MLP classifier. The network was trained, validated and tested and the results revealed that MLP could classify lying features into the three thermal categories with high overall accuracy (95.6%). The technique indicates that a combination of image processing, MLP classification and mathematical modelling can be used as a precise method for quantifying pig lying behaviour in welfare investigations. PMID- 27353418 TI - Impact of statin related media coverage on use of statins: interrupted time series analysis with UK primary care data. AB - OBJECTIVE: To quantify how a period of intense media coverage of controversy over the risk:benefit balance of statins affected their use. DESIGN: Interrupted time series analysis of prospectively collected electronic data from primary care. SETTING: Clinical Practice Research Datalink (CPRD) in the United Kingdom. PARTICIPANTS: Patients newly eligible for or currently taking statins for primary and secondary cardiovascular disease prevention in each month in January 2011-March 2015. MAIN OUTCOME MEASURES: Adjusted odds ratios for starting/stopping taking statins after the media coverage (October 2013-March 2014). RESULTS: There was no evidence that the period of high media coverage was associated with changes in statin initiation among patients with a high recorded risk score for cardiovascular disease (primary prevention) or a recent cardiovascular event (secondary prevention) (odds ratio 0.99 (95% confidence interval 0.87 to 1.13; P=0.92) and 1.04 (0.92 to 1.18; P=0.54), respectively), though there was a decrease in the overall proportion of patients with a recorded risk score. Patients already taking statins were more likely to stop taking them for both primary and secondary prevention after the high media coverage period (1.11 (1.05 to 1.18; P<0.001) and 1.12 (1.04 to 1.21; P=0.003), respectively). Stratified analyses showed that older patients and those with a longer continuous prescription were more likely to stop taking statins after the media coverage. In post hoc analyses, the increased rates of cessation were no longer observed after six months. CONCLUSIONS: A period of intense public discussion over the risks:benefit balance of statins, covered widely in the media, was followed by a transient rise in the proportion of people who stopped taking statins. This research highlights the potential for widely covered health stories in the lay media to impact on healthcare related behaviour. PMID- 27353420 TI - Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models. AB - BACKGROUND: Venetoclax, a small molecule BH3 mimetic which inhibits the anti apoptotic protein Bcl-2, and idasanutlin, a selective MDM2 antagonist, have both shown activity as single-agent treatments in pre-clinical and clinical studies in acute myeloid leukemia (AML). In this study, we deliver the rationale and molecular basis for the combination of idasanutlin and venetoclax for treatment of p53 wild-type AML. METHODS: The effect of idasanutlin and venetoclax combination on cell viability, apoptosis, and cell cycle progression was investigated in vitro using established AML cell lines. In vivo efficacy was demonstrated in subcutaneous and orthotopic xenograft models generated in female nude or non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Mode of-action analyses were performed by means of cell cycle kinetic studies, RNA sequencing as well as western blotting experiments. RESULTS: Combination treatment with venetoclax and idasanutlin results in synergistic anti-tumor activity compared with the respective single-agent treatments in vitro, in p53 wild-type AML cell lines, and leads to strongly superior efficacy in vivo, in subcutaneous and orthotopic AML models. The inhibitory effects of idasanutlin were cell-cycle dependent, with cells arresting in G1 in consecutive cycles and the induction of apoptosis only evident after cells had gone through at least two cell cycles. Combination treatment with venetoclax removed this dependency, resulting in an acceleration of cell death kinetics. As expected, gene expression studies using RNA sequencing showed significant alterations to pathways associated with p53 signaling and cell cycle arrest (CCND1 pathway) in response to idasanutlin treatment. Only few gene expression changes were observed for venetoclax treatment and combination treatment, indicating that their effects are mediated mainly at the post-transcriptional level. Protein expression studies demonstrated that inhibition of the anti-apoptotic protein Mcl-1 contributed to the activity of venetoclax and idasanutlin, with earlier inhibition of Mcl-1 in response to combination treatment contributing to the superior combined activity. The role of Mcl-1 was confirmed by small hairpin RNA gene knockdown studies. CONCLUSIONS: Our findings provide functional and molecular insight on the superior anti-tumor activity of combined idasanutlin and venetoclax treatment in AML and support its further exploration in clinical studies. PMID- 27353421 TI - French general practitioners' sense of isolation in the management of elderly cancer patients. AB - BACKGROUND: Cancer care in people over 75 years of age is particularly complex and requires collaboration between oncologists, geriatricians, GPs and other professional and family carers. To improve the care pathways for elderly people living with cancer, the French health authorities have created a network of oncologists and geriatricians; however, GPs experience difficulties in establishing their place in this network. OBJECTIVE: This study aimed to analyse the impressions of French GPs involved in the care of elderly patients with cancer, including their feelings regarding their relationships with their oncologist and geriatrician colleagues. METHODS: A qualitative approach using focus groups was employed. The proceedings of these focus groups were recorded, retranscribed and subjected to thematic analysis. RESULTS: Although heavily involved in the care of their elderly patients living with cancer, the GPs who participated reported feeling isolated in their role at each step during the course of the disease. The principal themes addressed were screening and diagnosis, therapeutic decisions, multidisciplinary consultation meetings, the announcement of the diagnosis and monitoring at home. Their relationships with their oncologist colleagues showed much room for improvement, and they were unaware of the oncogeriatric network. CONCLUSIONS: Improving the communication between GPs, oncologists and geriatric medicine seems to be one response to the isolation that GPs feel when caring for older people with cancer. At the primary care level, integration of GPs into the oncogeriatric network and the creation of a cancer care communication system in collaboration with the relevant hospital teams may be effective solutions. PMID- 27353422 TI - Glycemic and vascular choreoballism as main causes of secondary choreoballism involving the putamen. AB - BACKGROUND: The putamen is frequently involved in cases of secondary choreoballism (CB). To date, no study has investigated clinical features of secondary CB such as vascular CB (vCB) and glycemic CB (gCB) in view of putaminal involvement. OBJECTIVES: Cases of CB with putaminal lesions from our hospital were identified in hospital records. Historical cases were obtained from the MEDLINE database. Cases of gCB are defined as those with CB, diabetes mellitus and high signal intensities (HSIs) in the putamen on T1 weighted imaging (T1WI). Cases of vCB are identified among those with CB and stroke involving the putamen. RESULTS: A total of 284 cases (in-hospital cases, 11 gCB and 3 vCB; historical cases, 225 gCB and 45 vCB) were included after excluding 23 glycemic cases without HSIs on T1WI and 53 cases with non-glycemic etiologies. Persistence of CB was longer than one month in 84 cases (gCB, 36.9%, and vCB, 63.0%). Extra putaminal lesions occurred more frequently in vCB (71.1%) than gCB (50.7%). Age, cerebrovascular etiology and extra-putaminal lesions were found to be significant predictors for persistence of CB one month after onset. Female gender and extra putaminal lesions were significant predictors for persistence of CB one year after onset. CONCLUSIONS: gCB was the primary common cause of secondary CB involving the putamen. Older age, female gender, vascular etiologies and extensive lesions (putaminal and extra-putaminal) were significant predictors of CB persistence. PMID- 27353423 TI - miRNA in Macrophage Development and Function. AB - SIGNIFICANCE: MicroRNAs (miRNAs) control cellular gene expression via primarily binding to 3' or 5' untranslated region of the target transcript leading to translational repression or mRNA degradation. In most cases, miRNAs have been observed to fine-tune the cellular responses and, therefore, act as a rheostat rather than an on/off switch. Transcription factor PU.1 is a master switch that controls monocyte/macrophage development from hematopoietic stem cells. Recent Advances: PU.1 induces a specific set of miRNAs while suppressing the miR17-92 cluster to regulate monocyte/macrophage development. In addition to development, miRNAs tightly control the macrophage polarization continuum from proinflammatory M1 or proreparative M2 by regulating expression of key transcription factors involved in the process of polarization. CRITICAL ISSUES: miRNAs are intricately involved with fine-tuning fundamental macrophage functions such as phagocytosis, efferocytosis, inflammation, tissue repair, and tumor promotion. Macrophages are secretory cells that participate in intercellular communication by releasing regulatory molecules and microvesicles (MVs). MVs are bilayered lipid membranes packaging a hydrophilic cargo, including proteins and nucleic acids. Macrophage derived MVs carry functionally active miRNAs that suppress gene expression in target cells via post-transcriptional gene silencing, thus regulating cell function. In summary, miRNAs fine-tune several major facets of macrophage development and function. Such fine-tuning is critical in preventing exaggerated macrophage response to endogenous or exogenous stimuli. FUTURE DIRECTIONS: A critical role of miRNAs in the regulation of innate immune response and macrophage biology, including development, differentiation, and activation, has emerged. A clear understanding of such regulation on macrophage function remains to be elucidated. Antioxid. Redox Signal. 25, 795-804. PMID- 27353424 TI - Efficient production of multi-modified pigs for xenotransplantation by 'combineering', gene stacking and gene editing. AB - Xenotransplantation from pigs could alleviate the shortage of human tissues and organs for transplantation. Means have been identified to overcome hyperacute rejection and acute vascular rejection mechanisms mounted by the recipient. The challenge is to combine multiple genetic modifications to enable normal animal breeding and meet the demand for transplants. We used two methods to colocate xenoprotective transgenes at one locus, sequential targeted transgene placement - 'gene stacking', and cointegration of multiple engineered large vectors - 'combineering', to generate pigs carrying modifications considered necessary to inhibit short to mid-term xenograft rejection. Pigs were generated by serial nuclear transfer and analysed at intermediate stages. Human complement inhibitors CD46, CD55 and CD59 were abundantly expressed in all tissues examined, human HO1 and human A20 were widely expressed. ZFN or CRISPR/Cas9 mediated homozygous GGTA1 and CMAH knockout abolished alpha-Gal and Neu5Gc epitopes. Cells from multi transgenic piglets showed complete protection against human complement-mediated lysis, even before GGTA1 knockout. Blockade of endothelial activation reduced TNFalpha-induced E-selectin expression, IFNgamma-induced MHC class-II upregulation and TNFalpha/cycloheximide caspase induction. Microbial analysis found no PERV-C, PCMV or 13 other infectious agents. These animals are a major advance towards clinical porcine xenotransplantation and demonstrate that livestock engineering has come of age. PMID- 27353425 TI - Urinary albumin-to-creatinine ratio is associated with endothelial dysfunction in HIV-infected patients receiving antiretroviral therapy. AB - Endothelial dysfunction, a marker of cardiovascular (CV) risk, is common in human immunodeficiency virus (HIV)-infected patients. Microalbuminuria is frequent in HIV-infected patients, and is a predictor of renal impairment and CV risk. We investigated the association between microalbuminuria and endothelial dysfunction among HIV-infected patients receiving highly-active antiretroviral therapy (HAART). Endothelial function, measured by brachial artery flow-mediated dilatation (bFMD), and urine albumin-to-creatinine ratio (UACR), were measured in 170 HAART-treated HIV-infected adults. The relationship between UACR and bFMD was evaluated. The prevalence of increased UACR, defined by two cut-off levels (20 mg/g and 30 mg/g), was 29% and 17%. UACR was significantly higher while bFMD was lower among patients with metabolic syndrome (MS). UACR was associated with bFMD (r = -0.31; p < 0.001). This association was stronger in MS-patients (r = -0.44; p = 0.003). UACR above 20 mg/g was associated with an increased risk (OR 2.37, 95% CI 1.15-4.89, p = 0.020) of severely impaired bFMD (bFMD <= 2.1%). Patients with MS and increased UACR had the lowest bFMD compared with those with none or one of the two conditions. Microalbuminuria and endothelial dysfunction are positively associated in HIV-infected patients regardless of known confounders. The coexistence of microalbuminuria and MS amplifies their deleterious influence on endothelial function. PMID- 27353426 TI - Training professionals to engage agriculture as an instrument of public health. PMID- 27353427 TI - The actin crosslinking protein palladin modulates force generation and mechanosensitivity of tumor associated fibroblasts. AB - Cells organize actin filaments into higher-order structures by regulating the composition, distribution and concentration of actin crosslinkers. Palladin is an actin crosslinker found in the lamellar actin network and stress fibers, which are critical for mechanosensing of the environment. Palladin also serves as a molecular scaffold for alpha-actinin, another key actin crosslinker. By virtue of its close interactions with actomyosin structures in the cell, palladin may play an important role in cell mechanics. However, the role of palladin in cellular force generation and mechanosensing has not been studied. Here, we investigate the role of palladin in regulating the plasticity of the actin cytoskeleton and cellular force generation in response to alterations in substrate stiffness. Traction force microscopy revealed that tumor-associated fibroblasts generate larger forces on substrates of increased stiffness. Contrary to expectations, knocking down palladin increased the forces generated by cells and inhibited their ability to sense substrate stiffness for very stiff gels. This was accompanied by significant differences in actin organization, adhesion dynamics and altered myosin organization in palladin knock-down cells. Our results suggest that actin crosslinkers such as palladin and myosin motors coordinate for optimal cell function and to prevent aberrant behavior as in cancer metastasis. PMID- 27353428 TI - Experimentally simulating quantum walks with self-collimated light. AB - In self-collimated photonic crystal, periodically arranged air holes of sub wavelength scale provide flattened equi-frequency curves perpendicular to the GammaM direction, which allow light or photons propagating in a quasi-uniform medium without diffraction. Here we for the first time experimentally simulate four-step single-photon discrete time quantum walks with classical light in such a photonic crystal chip fabricated on silicon-on-insulator. Similarities between theoretical expectations and experimental results are higher than 0.98. The functional area is compact and can be extended to construct more complicated linear quantum circuits. PMID- 27353429 TI - The IL-17-Th1/Th17 pathway: an attractive target for lung cancer therapy? AB - INTRODUCTION: There is strong pharmaceutical development of agents targeting the IL-17-TH17 pathway for the treatment of psoriasis (Ps) and psoriatic arthritis (PsA). Lung cancer accounts for 28% of all cancer-related deaths worldwide, and roughly 80% of patients with newly-diagnosed non-small cell lung cancer (NSCLC) present with metastatic disease, with a poor prognosis of around 12 months. Therefore, there is a high unmet medical need for the development of new and potent systemic treatments in this deadly disease. The emergence of immunotherapies such as anti-PD-1 or anti-PDL1 as candidate therapies in non small cell lung cancer (NSCLC) indicates that targeting critical immuno modulatory cytokines including those within the IL-17-Th1/Th17 axis may have proven benefit in the treatment of lung cancer. Areas covered: In this review we describe the current evidence for aberrant IL-17-Th1/Th17 settings in cancer, particularly with regard to targeting this axis in NSCLC. We further discuss the current agents under pharmaceutical development which could potentially target this axis, and discuss the current limitations and areas of concern regarding the use of these in lung cancer. Expert opinion: Current evidence suggests that moving forward agents targeting the IL-17-Th1/Th17 pathway may have novel new oncoimmunology indications in the treatment paradigm for NSCLC. PMID- 27353430 TI - Detecting Memory Impairment in Deaf People: A New Test of Verbal Learning and Memory in British Sign Language. AB - OBJECTIVE: Most existing tests of memory and verbal learning in adults were created for spoken languages, and are unsuitable for assessing deaf people who rely on signed languages. In response to this need for sign language measures, the British Sign Language Verbal Learning and Memory Test (BSL-VLMT) was developed. It follows the format of the English language Hopkins Verbal Learning Test Revised, using standardized video-presentation with novel stimuli and instructions wholly in British Sign Language, and no English language requirement. METHOD: Data were collected from 223 cognitively healthy deaf signers aged 50-89 and 12 deaf patients diagnosed with dementia. Normative data percentiles were derived for clinical use, and receiver-operating characteristic curves computed to explore the clinical potential and diagnostic sensitivity and specificity. RESULTS: The test showed good discrimination between the normative and clinical samples, providing preliminary evidence of clinical utility for identifying learning and memory impairment in older deaf signers with neurodegeneration. CONCLUSIONS: This innovative video testing approach transforms the ability to accurately detect memory impairments in deaf people and avoids the problems of using interpreters, with international potential for adapting similar tests into other signed languages. PMID- 27353431 TI - Standardization, Clinical Validation, and Typicality Norms of a New Test Assessing Semantic Verbal Fluency. AB - OBJECTIVE: Semantic verbal fluency (SVF) tests are widely used in clinical neuropsychology. We propose the standardization and clinical validation of a new SVF test based on the production of names of birds and articles of furniture (Birds and Articles of Furniture test-BAF). METHODS: A sample of 268 subjects aged 40 years or more underwent the test. The clinical validation was conducted on subjects affected by amnesic Mild Cognitive Impairment (aMCI; N = 106), mild (N = 178), and moderate (N = 114) Alzheimer's disease (AD). RESULTS: The BAF total score was influenced by both age and education, whereas the single scores obtained on BAF were also influenced by gender. The percentage of subjects with pathological score on BAF increased from aMCI (19%) to mild (45.5%) and moderate (71.1%) AD, and receiver operating characteristic curves analysis showed that the BAF may be highly reliable in distinguishing aMCI and AD patients from healthy subjects. We also provide typicality norms for birds and articles of furniture that could be useful in the assessment of qualitative features of words produced in semantic fluency tests. CONCLUSIONS: The BAF test could be a valid and reliable tool in both clinical practice and research on subjects affected by cognitive impairment. PMID- 27353432 TI - Gaseous product mixture from Fischer-Tropsch synthesis as an efficient carbon feedstock for low temperature CVD growth of carbon nanotube carpets. AB - Low-temperature chemical vapor deposition (CVD) growth of carbon nanotube (CNT) carpets from Fe and Fe-Cu catalysts using a gaseous product mixture from Fischer Tropsch synthesis (FTS-GP) as a superior carbon feedstock is demonstrated. This growth approach addresses a persistent issue of obtaining thick CNT carpets on temperature-sensitive substrates at low temperatures using a non-plasma CVD approach without catalyst pretreatment and/or preheating of the carbon feedstock. The efficiency of the process is evidenced by the highly dense, vertically aligned CNT structures from both Fe and Fe-Cu catalysts even at temperatures as low as 400 degrees C - a record low growth temperature for CNT carpets obtained via conventional thermal CVD. The grown CNTs exhibit a straight morphology with hollow interior and parallel graphitic planes along the tube walls. The apparent activation energies for CNT carpet growth on Fe and Fe-Cu catalysts are 0.71 and 0.54 eV, respectively. The synergistic effect of Fe and Cu show a strong dependence on the growth temperature, with Cu being more influential at temperatures higher than 450 degrees C. The low activation energies and long catalyst lifetimes observed are rationalized based on the unique composition of FTS-GP and Gibbs free energies for the decomposition reactions of the hydrocarbon components. The use of FTS-GP facilitates low-temperature growth of CNT carpets on traditional (alumina film) and nontraditional substrates (aluminum foil) and has the potential of enhancing CNT quality, catalyst lifetime, and scalability. PMID- 27353433 TI - The macroecology of infectious diseases: a new perspective on global-scale drivers of pathogen distributions and impacts. AB - Identifying drivers of infectious disease patterns and impacts at the broadest scales of organisation is one of the most crucial challenges for modern science, yet answers to many fundamental questions remain elusive. These include what factors commonly facilitate transmission of pathogens to novel host species, what drives variation in immune investment among host species, and more generally what drives global patterns of parasite diversity and distribution? Here we consider how the perspectives and tools of macroecology, a field that investigates patterns and processes at broad spatial, temporal and taxonomic scales, are expanding scientific understanding of global infectious disease ecology. In particular, emerging approaches are providing new insights about scaling properties across all living taxa, and new strategies for mapping pathogen biodiversity and infection risk. Ultimately, macroecology is establishing a framework to more accurately predict global patterns of infectious disease distribution and emergence. PMID- 27353434 TI - Extracellular Matrix of Current Biological Scaffolds Promotes the Differentiation Potential of Mesenchymal Stem Cells. AB - PURPOSE: The purpose of this study was to quantitatively assess the ability of bone marrow-derived mesenchymal stem cells (bMSC) to differentiate toward bone, fat, cartilage, and tendon lineages when grown on commercially available scaffolds compared with control and native tendon tissue. METHODS: BMSCs were cultured and analyzed by fluorescent automated cells sorting for surface markers CD73, -90, and -105. BMSCs were grown on rotator cuff tendon (RCT), decellularized human dermis patch (DDP), bilayer collagen matrix, and fibrin matrix (FM) to test their differentiation potential using quantitative polymerase chain reaction and establish markers for osteogenic, adipogenic, chondrogenic, and tenogenic lineages. Immunocytochemical testing was used to determine the specific proteins present on the scaffolds. RESULTS: Alkaline phosphatase and osteocalcin gene expression was significantly higher on RCT (P < .001) and collagen scaffold (CS) (P < .001) compared with DDP and FM scaffolds (P < .001, P < .001). When differentiated toward a cartilage lineage, bMSCs grown on CS had significantly more type II collagen and aggrecan compared with DDP (P < .001, P < .001), FM (P < .001, P < .001), and RCT (P < .001, P < .001). Differentiated bMSCs grown on the CS had a significant increase in PPARgamma and FABP4 gene expression compared with bMSCs grown on all other scaffolds (all P < .001). The differentiation of bMSCs into tendon on CSs had significantly more tenacin C, decorin, and type III collagen gene expression when compared with RCT, DDP, and FM (all P < .001). Decorin gene expression in the control undifferentiated CS was also significantly increased, suggesting that the matrix alone may promote a tenogenic lineage (P = .637). CONCLUSIONS: Differences in the extracellular matrix composition of scaffolds significantly impact their potential to promote differentiation of bMSCs. Comparing the native RCT to the tested scaffolds showed that a high content of type I and III collagen significantly increased the potential of bMSCs to differentiate toward bone, tendon, fat, and cartilage lineages. CLINICAL RELEVANCE: This in vitro study shows the differences between commercially available scaffolds for rotator cuff repairs. Therefore, these results support clinical use depending on the surgical intention and the potential of bMSCs to differentiate into bone, tendon, cartilage, and fat tissue. PMID- 27353436 TI - Immunochemical and molecular assessment of urothelial neoplasms and aspects of the 2016 World Health Organization classification. AB - The new World Health Organization classification of tumours of the urinary system and male genital organs (4th edn) has several changes from previous versions, and was published in January 2016. New pathways have been discovered in the development of bladder cancer, and were included in this new classification. Guidance from the International Collaboration on Cancer Reporting (ICCR) helped to clarify open questions, in conjunction with the new classification. The histological groups of urothelial carcinoma evolved. Grading remained the same, despite controversy among European urologists. Substaging of pT1 tumours is recommended for the first time, and the ICCR has made recommendations on how to report this. Furthermore, worldwide advice has been published on the use of immunohistochemistry, and recommendations have been made to try to standardize the handling of bladder cancer from a histopathological point of view. At a molecular level, bladder cancer groups have been stratified, and an upcoming molecular classification permits a novel view of this malignancy. This review will try to summarize the most important changes. PMID- 27353437 TI - Chemical and in vitro biological information to predict mouse liver toxicity using recursive random forests. AB - In this study, recursive random forests were used to build classification models for mouse liver toxicity. The mouse liver toxicity endpoint (67 toxic and 166 non toxic) was a composition of four in vivo chronic systemic and carcinogenic toxicity endpoints (non-proliferative, neoplastic, proliferative and gross pathology). A multiple under-sampling approach and a shifted classification threshold of 0.288 (non-toxic < 0.288 and toxic >= 0.288) were used to cope with the unbalanced data. Our study showed that recursive random forests are very efficient in variable selection and for the development of predictive in silico models. Generally, over 95% redundant descriptors could be reduced from modelling for all the chemical, biological and hybrid models in this study. The predictive performance of chemical models (CCR of 0.73) is comparable with hybrid model performance (CCR of 0.74). Descriptors related to the octanol-water partition coefficient are vital for model performance. The in vitro endpoint of CYP2A2 played a key role in the development and interpretation of hybrid models. Identifying high-throughput screening assays relevant to liver toxicity would be key for improving in silico models of liver toxicity. PMID- 27353438 TI - Interferon-Gamma and Fas Are Involved in Porphyromonas gingivalis-Induced Apoptosis of Human Extravillous Trophoblast-Derived HTR8/SVneo Cells via Extracellular Signal-Regulated Kinase 1/2 Pathway. AB - BACKGROUND: A number of studies recently revealed a link between periodontal disease and preterm birth (PTB). PTB can be induced by dental infection with Porphyromonas gingivalis (Pg), a periodontopathic bacterium. This study aims to investigate responses of human extravillous trophoblast-derived HTR8/SVneo cells to Pg infection. METHODS: Cell apoptosis, cell viability, protein expression, and cytokine production in HTR8 cells were measured via: 1) flow cytometry, 2) CCK-8 assay, 3) western blot, and 4) enzyme-linked immunosorbent assay methods, respectively. RESULTS: Pg decreased cell viability and increased cell apoptosis, active caspase-3 and Fas expression, and interferon-gamma (IFN-gamma) secretion in HTR8 cells. Extracellular signal-regulated kinase (ERK) 1/2 inhibitor U0126 and FasL neutralizing antibody NOK1 that blocks FasL/Fas interaction both significantly suppressed Pg-induced apoptosis. U0126 also inhibited IFN-gamma secretion and Fas expression close to control levels. Moreover, treatment with recombinant IFN-gamma also significantly decreased number of viable HTR8 cells and increased Fas expression, suggesting IFN-gamma may play an important role in Pg-induced apoptosis of HTR8 cells, at least partially through regulation of Fas expression. CONCLUSIONS: To the best of the authors' knowledge, this is the first study to demonstrate Pg induces IFN-gamma secretion, Fas expression, and apoptosis in human extravillous trophoblast-derived HTR8/SVneo cells in an ERK1/2 dependent manner, and IFN-gamma (explored by recombinant IFN-gamma) and Fas are involved in Pg-induced apoptosis. The finding that Pg infection abnormally regulates inflammation and apoptosis of human trophoblasts may give new insights into the possible link of PTB with maternal periodontal disease and periodontal pathogens. PMID- 27353439 TI - Clinical Usefulness of Novel Immunochromatographic Detection Device for Porphyromonas gingivalis in Evaluating Effects of Scaling and Root Planing and Local Antimicrobial Therapy. AB - BACKGROUND: The authors have previously reported development of a novel immunochromatographic device (DK13-PG-001) for specific detection of Porphyromonas gingivalis (Pg). In this study, clinical usefulness of the detection device during periodontal therapy is presented. METHODS: The multicenter study was conducted with 62 patients contributing 118 periodontitis sites with probing depth (PD) of 4 to 9 mm. Subgingival plaque samples were used for detection of Pg by DK13-PG-001 and the PCR-invader method at: 1) baseline (BL); 2) reevaluation (RE; after scaling and root planing); and 3) final evaluation (FE; after local drug delivery system). Periodontal examinations were performed concurrently with the test for Pg detection. Plasma immunoglobulin G (IgG) titers against Pg were also determined in patients using an enzyme-linked immunosorbent assay. RESULTS: DK13-PG-001 score and number of Pg by the PCR invader method showed a strong correlation (r = 0.862) at three stages during periodontal therapy (n = 354). High sensitivity and specificity of DK13-PG-001, in comparison with the PCR-invader method, were shown. A significant correlation was found among device score, number of Pg by the PCR-invader method, and PD and clinical attachment level at BL and RE. Plasma IgG titers against Pg were significantly reduced at FE in comparison with BL. Weak but significant correlations between IgG titers and device scores were shown at BL and FE. CONCLUSION: Results suggest the DK13-PG-001 device is a useful tool for detection of Pg in dental offices and can aid clinical evaluation of the extent of periodontitis and therapeutic efficacy. PMID- 27353440 TI - Preliminary Results of Non-Surgical Periodontal Treatment in Patients With Breast Cancer Undergoing Chemotherapy. AB - BACKGROUND: Although priority is often given to treat the cancer itself, focus should also be directed to prevention and improvement of oral complications that may occur as a result of cancer and/or its treatment. This study compares periodontal treatment results in healthy patients and patients with breast cancer undergoing chemotherapy by monitoring clinical conditions and C-reactive-protein (CRP) levels. METHODS: Thirty-five participants were allocated to one of two groups: patients with periodontitis (P) (n = 18) and patients with breast cancer and periodontitis (CAN/P) (n = 17). The following clinical parameters were assessed at baseline and 45, 90, and 180 days after non-surgical periodontal treatment (NSPT): 1) probing depth (PD); 2) clinical attachment level (CAL); 3) plaque index (PI); 4) gingival index (GI); 5) CRP; and 6) complete blood count. Clinical parameters and CRP levels were statistically analyzed. RESULTS: P and CAN/P groups presented a statistically significant decrease in PD after NSPT at 45, 90, and 180 days compared with baseline (P <0.05). There was a CAL gain in the P group and a significant reduction in PI and GI at 45, 90, and 180 days for both groups (P <0.05). At 180 days after NSPT treatment, the CAN/P group showed a higher number of residual pockets (P <0.05) compared with the P group (46.48 +/- 26.80 and 7.58 +/- 7.40, respectively). The P group demonstrated a significant reduction in CRP levels at 45 and 180 days after NSPT compared with baseline (P <0.05), whereas this reduction was not observed in the CAN/P group. CONCLUSION: Patients with breast cancer who were undergoing chemotherapy responded to periodontal non-surgical therapy, although with less favorable results than patients with periodontitis without cancer, and may require additional or adjunctive periodontal treatments. PMID- 27353441 TI - Clinical and Radiographic Evaluation of Demineralized Freeze-Dried Bone Allograft Versus Platelet-Rich Fibrin for the Treatment of Periodontal Intrabony Defects in Humans. AB - BACKGROUND: A wide variety of materials have been proposed for treatment of periodontal intrabony defects (IBDs); recently, platelet-rich fibrin (PRF) has been suggested as a grafting material. The aim of this study is to report changes in clinical attachment level (CAL) and bone fill of periodontal IBDs treated with demineralized freeze-dried bone allograft (DFDBA) compared with PRF in humans. METHODS: Thirty-six patients completed the study protocol. Each patient contributed a single IBD, which was randomized to receive either DFDBA or PRF. Clinical and standardized radiographic data were collected at baseline and 6 months after treatment. Primary outcome measures included: 1) radiographic bone fill as measured from the cemento-enamel junction to base of bony defect and 2) change in CAL. RESULTS: Both treatment groups had significant gains in CAL as well as bone fill, with no significant differences in outcomes between groups. DFDBA had a mean CAL gain of 1.16 +/- 1.33 mm, mean clinical bone fill of 1.53 +/ 1.64 mm, and mean radiographic bone fill of 1.14 +/- 0.88 mm. PRF had a mean CAL gain of 1.03 +/- 0.86 mm, mean clinical bone fill of 1.35 +/- 1.60 mm, and mean radiographic bone fill of 1.10 +/- 1.01 mm. CONCLUSION: Treatment of IBDs with either DFDBA or PRF resulted in a significant gain in CAL as well as bone fill after 6 months of healing, with no significant difference between materials. PMID- 27353442 TI - Characterization of a putative ArsR transcriptional regulator encoded by Rv2642 from Mycobacterium tuberculosis. PMID- 27353443 TI - Rhodopsin kinase and arrestin binding control the decay of photoactivated rhodopsin and dark adaptation of mouse rods. AB - Photoactivation of vertebrate rhodopsin converts it to the physiologically active Meta II (R*) state, which triggers the rod light response. Meta II is rapidly inactivated by the phosphorylation of C-terminal serine and threonine residues by G-protein receptor kinase (Grk1) and subsequent binding of arrestin 1 (Arr1). Meta II exists in equilibrium with the more stable inactive form of rhodopsin, Meta III. Dark adaptation of rods requires the complete thermal decay of Meta II/Meta III into opsin and all-trans retinal and the subsequent regeneration of rhodopsin with 11-cis retinal chromophore. In this study, we examine the regulation of Meta III decay by Grk1 and Arr1 in intact mouse rods and their effect on rod dark adaptation. We measure the rates of Meta III decay in isolated retinas of wild-type (WT), Grk1-deficient (Grk1(-/-)), Arr1-deficient (Arr1(-/ )), and Arr1-overexpressing (Arr1(ox)) mice. We find that in WT mouse rods, Meta III peaks ~6 min after rhodopsin activation and decays with a time constant (tau) of 17 min. Meta III decay slows in Arr1(-/-) rods (tau of ~27 min), whereas it accelerates in Arr1(ox) rods (tau of ~8 min) and Grk1(-/-) rods (tau of ~13 min). In all cases, regeneration of rhodopsin with exogenous 11-cis retinal is rate limited by the decay of Meta III. Notably, the kinetics of rod dark adaptation in vivo is also modulated by the levels of Arr1 and Grk1. We conclude that, in addition to their well-established roles in Meta II inactivation, Grk1 and Arr1 can modulate the kinetics of Meta III decay and rod dark adaptation in vivo. PMID- 27353444 TI - Syndromic deafness mutations at Asn 14 differentially alter the open stability of Cx26 hemichannels. AB - Connexin 26 (Cx26) is a transmembrane protein that forms hexameric hemichannels that can function when unopposed or dock to form intercellular gap junction channels. Aberrantly functioning unopposed hemichannels are a common feature of syndromic deafness associated with mutations in Cx26. In this study, we examine two different mutations at the same position in the N-terminal domain of Cx26, N14K and N14Y, which have been reported to produce different phenotypes in patients. We find that both N14K and N14Y, when expressed alone or together with wild-type (WT) Cx26, result in functional hemichannels with widely disparate functional properties. N14K currents are robust, whereas N14Y currents are small. The two mutants also exhibit opposite shifts in voltage-dependent loop gating, such that activation of N14K and N14Y is shifted in the hyperpolarizing and depolarizing directions, respectively. Deactivation kinetics suggests that N14K stabilizes and N14Y destabilizes the open state. Single N14K hemichannel recordings in low extracellular Ca(2+) show no evidence of stable closing transitions associated with loop gating, and N14K hemichannels are insensitive to pH. Together, these properties cause N14K hemichannels to be particularly refractory to closing. Although we find that the unitary conductance of N14K is indistinguishable from WT Cx26, mutagenesis and substituted cysteine accessibility studies suggest that the N14 residue is exposed to the pore and that the differential properties of N14K and N14Y hemichannels likely result from altered electrostatic interactions between the N terminus and the cytoplasmic extension of TM2 in the adjacent subunit. The combined effects that we observe on loop gating and pH regulation may explain the unusual buccal cutaneous manifestations in patients carrying the N14K mutation. Our work also provides new considerations regarding the underlying molecular mechanism of loop gating, which controls hemichannel opening in the plasma membrane. PMID- 27353445 TI - Improved resolution of single channel dwell times reveals mechanisms of binding, priming, and gating in muscle AChR. AB - The acetylcholine receptor (AChR) from vertebrate skeletal muscle initiates voluntary movement, and its kinetics of activation are crucial for maintaining the safety margin for neuromuscular transmission. Furthermore, the kinetic mechanism of the muscle AChR serves as an archetype for understanding activation mechanisms of related receptors from the Cys-loop superfamily. Here we record currents through single muscle AChR channels with improved temporal resolution approaching half an order of magnitude over our previous best. A range of concentrations of full and partial agonists are used to elicit currents from human wild-type and gain-of-function mutant AChRs. For each agonist-receptor combination, rate constants are estimated from maximum likelihood analysis using a kinetic scheme comprised of agonist binding, priming, and channel gating steps. The kinetic scheme and rate constants are tested by stochastic simulation, followed by incorporation of the experimental step response, sampling rate, background noise, and filter bandwidth. Analyses of the simulated data confirm all rate constants except those for channel gating, which are overestimated because of the established effect of noise on the briefest dwell times. Estimates of the gating rate constants were obtained through iterative simulation followed by kinetic fitting. The results reveal that the agonist association rate constants are independent of agonist occupancy but depend on receptor state, whereas those for agonist dissociation depend on occupancy but not on state. The priming rate and equilibrium constants increase with successive agonist occupancy, and for a full agonist, the forward rate constant increases more than the equilibrium constant; for a partial agonist, the forward rate and equilibrium constants increase equally. The gating rate and equilibrium constants also increase with successive agonist occupancy, but unlike priming, the equilibrium constants increase more than the forward rate constants. As observed for a full and a partial agonist, the gain-of-function mutation affects the relationship between rate and equilibrium constants for priming but not for channel gating. Thus, resolving brief single channel currents distinguishes priming from gating steps and reveals how the corresponding rate and equilibrium constants depend on agonist occupancy. PMID- 27353446 TI - Patch-clamp fluorometry-based channel counting to determine HCN channel conductance. AB - Counting ion channels on cell membranes is of fundamental importance for the study of channel biophysics. Channel counting has thus far been tackled by classical approaches, such as radioactive labeling of ion channels with blockers, gating current measurements, and nonstationary noise analysis. Here, we develop a counting method based on patch-clamp fluorometry (PCF), which enables simultaneous electrical and optical recordings, and apply it to EGFP-tagged, hyperpolarization-activated and cyclic nucleotide-regulated (HCN) channels. We use a well-characterized and homologous cyclic nucleotide-gated (CNG) channel to establish the relationship between macroscopic fluorescence intensity and the total number of channels. Subsequently, based on our estimate of the total number of HCN channels, we determine the single-channel conductance of HCN1 and HCN2 to be 0.46 and 1.71 pS, respectively. Such a small conductance would present a technical challenge for traditional electrophysiology. This PCF-based technique provides an alternative method for counting particles on cell membranes, which could be applied to biophysical studies of other membrane proteins. PMID- 27353447 TI - A new mechanism for dendritic pattern formation in dense systems. AB - Patterns are often formed when particles cluster: Since patterns reflect the connectivity of different types of material, the emergence of patterns affects the physical and chemical properties of systems and shares a close relationship to their macroscopic functions. A radial dendritic pattern (RDP) is observed in many systems such as snow crystals, polymer crystals and biological systems. Although most of these systems are considered as dense particle suspensions, the mechanism of RDP formation in dense particle systems is not yet understood. It should be noted that the diffusion limited aggregation model is not applicable to RDP formation in dense systems, but in dilute particle systems. Here, we propose a simple model that exhibits RDP formation in a dense particle system. The model potential for the inter-particle interaction is composed of two parts, a repulsive and an attractive force. The repulsive force is applied to all the particles all the time and the attractive force is exerted only among particles inside a circular domain, which expands at a certain speed as a wave front propagating from a preselected centre. It is found that an RDP is formed if the velocity of the wave front that triggers the attractive interaction is of the same order of magnitude as the time scale defined by the aggregation speed. PMID- 27353448 TI - Mental health nurses' views about antipsychotic medication side effects. AB - WHAT IS KNOWN ON THE SUBJECT?: The only previous quantitative study that examined nurses' use of assessment tools to identify antipsychotic medication side effects found that about 25% of mental health nurses were using assessment tools. No previous studies have examined factors that influence the manner in which mental health nurses assess antipsychotic medication side effects. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: One-third of the respondents were not aware of any antipsychotic medication side-effect assessment tool, and only one-quarter were currently using an assessment tool. 'Service responsibility' was significantly associated with ongoing use of antipsychotic medication assessment tools, indicating that respondents with more positive attitudes to their service were more likely to continue using antipsychotic medication assessment tools. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The low level of awareness and use of antipsychotic medication side-effect assessment tools indicates that nursing educational institutions should incorporate more detail about these tools in course content, and emphasize in particular the benefits that result from the use of these tools in clinical practice. Service processes contributed significantly to the use of antipsychotic medication assessment tools, which indicates that managers need to foster workplace cultures that promote routine use of these tools. ABSTRACT: Introduction Limited evidence suggests that only a minority of mental health nurses regularly use standardized assessment tools to assess antipsychotic medication side effects, but the factors that contribute to the non routine use of these tools remain unknown. Aim To examine Australian mental health nurses' awareness of, and attitudes towards, side-effect assessment tools, and also identify factors the influence the use of these tools. Methods A cross sectional survey was undertaken through distributing an online questionnaire via email to members of the Australian College of Mental Health Nurses. Completed questionnaires were received from 171 respondents. Linear regression was used to examine the relationship between the 'service responsibility' and 'personal confidence' scale scores, and awareness, previous use and ongoing use of antipsychotic medication assessment tools. Results Only one-quarter of the respondents (26.5%) were currently using an assessment tool. 'Service responsibility' was significantly associated with ongoing use of antipsychotic medication assessment tools (Beta = 3.26; 95% CI 0.83-5.69). 'Personal confidence' did not influence the ongoing use of assessment tools (Beta = -0.05; 95% CI -1.06-1.50). Implications for clinical practice Stakeholders can incorporate 'service responsibility' processes to foster increased use of assessment tools, which may enhance the identification antipsychotic medication side effects and improve the quality of care for service users. PMID- 27353449 TI - Child-Adult Relationship Enhancement in Primary Care (PriCARE): A Randomized Trial of a Parent Training for Child Behavior Problems. AB - OBJECTIVE: Child-Adult Relationship Enhancement in Primary Care (PriCARE) is a 6 session group parent training designed to teach positive parenting skills. Our objective was to measure PriCARE's impact on child behavior and parenting attitudes. METHODS: Parents of children 2 to 6 years old with behavior concerns were randomized to PriCARE (n = 80) or control (n = 40). Child behavior and parenting attitudes were measured at baseline (0 weeks), program completion (9 weeks), and 7 weeks after program completion (16 weeks) using the Eyberg Child Behavior Inventory (ECBI) and the Adult Adolescent Parenting Inventory 2 (AAPI2). Linear regression models compared mean ECBI and AAPI2 change scores from 0 to 16 weeks in the PriCARE and control groups, adjusted for baseline scores. RESULTS: Of those randomized to PriCARE, 43% attended 3 or more sessions. Decreases in mean ECBI intensity and problem scores between 0 and 16 weeks were greater in the PriCARE group, reflecting a larger improvement in behavior problems [intensity: 22 (-29, -16) vs -7 (-17, 2), P = .012; problem: -5 (-7, -4) vs -2 (-4, 0), P = .014]. Scores on 3 of the 5 AAPI2 subscales reflected greater improvements in parenting attitudes in the PriCARE group compared to control in the following areas: empathy toward children's needs [0.82 (0.51, 1.14) vs 0.25 (-0.19, 0.70), P = .04], corporal punishment [0.22 (0.00, 0.45) vs -0.30 (-0.61, 0.02), P = .009], and power and independence [0.37 (-0.02, 0.76) vs -0.64 (-1.19, -0.09), P = .003]. CONCLUSIONS: PriCARE shows promise in improving parent-reported child behavior problems in preschool-aged children and increasing positive parenting attitudes. PMID- 27353451 TI - Cell discharge correlates of posterior hypothalamic theta rhythm. Recipe for success in recording stable field potential. AB - The theta rhythm discovered in the posterior hypothalamus area (PHa) differs from theta observed in the hippocampal formation. In comparison to hippocampal spontaneous theta, the theta recorded in the PHa is rarely registered, has lower amplitude, often disappears, and sometimes returns after a few minutes. These features indicate that spontaneous theta recorded in the PHa is not an appropriate experimental model to search for the correlation between PHa cell discharges and local field potential. In this paper we present standard experimental conditions necessary to record theta-related cells in the PHa in anesthetized rats. Three pharmacological agents were used in the experiments to induce PHa theta rhythm in urethanized rats: carbachol (CCH), carbenoxolone and kainic acid, which are potent enough to induce well-synchronized PHa theta. However, CCH was found to be the best pharmacological tool to induce PHa theta oscillations, due to its longest duration of action and lack of preliminary epileptogenic effects. It seems that CCH-induced theta can be the most suitable pharmacological model for experiments with the use of protocol of long-lasting recordings of PHa theta-related cell discharges. PMID- 27353450 TI - The genetic regulatory signature of type 2 diabetes in human skeletal muscle. AB - Type 2 diabetes (T2D) results from the combined effects of genetic and environmental factors on multiple tissues over time. Of the >100 variants associated with T2D and related traits in genome-wide association studies (GWAS), >90% occur in non-coding regions, suggesting a strong regulatory component to T2D risk. Here to understand how T2D status, metabolic traits and genetic variation influence gene expression, we analyse skeletal muscle biopsies from 271 well phenotyped Finnish participants with glucose tolerance ranging from normal to newly diagnosed T2D. We perform high-depth strand-specific mRNA-sequencing and dense genotyping. Computational integration of these data with epigenome data, including ATAC-seq on skeletal muscle, and transcriptome data across diverse tissues reveals that the tissue-specific genetic regulatory architecture of skeletal muscle is highly enriched in muscle stretch/super enhancers, including some that overlap T2D GWAS variants. In one such example, T2D risk alleles residing in a muscle stretch/super enhancer are linked to increased expression and alternative splicing of muscle-specific isoforms of ANK1. PMID- 27353453 TI - Observation of intracellular interactions between DNA origami and lysosomes by the fluorescence localization method. AB - We obtained the fluorescence localization images of tube DNA origami nanostructures in NIH 3T3 cells for the first time. The fluorescence localization images of tube DNA origami nanostructures and TIRF images of lysosomes were combined and they revealed the detailed interactions between the two structures. Quantitative analysis illustrated that the tube origami can be captured as well as degraded by lysosomes with time. PMID- 27353452 TI - Predicting the diagnosis of autism in adults using the Autism-Spectrum Quotient (AQ) questionnaire. AB - BACKGROUND: Many adults with autism spectrum disorder (ASD) remain undiagnosed. Specialist assessment clinics enable the detection of these cases, but such services are often overstretched. It has been proposed that unnecessary referrals to these services could be reduced by prioritizing individuals who score highly on the Autism-Spectrum Quotient (AQ), a self-report questionnaire measure of autistic traits. However, the ability of the AQ to predict who will go on to receive a diagnosis of ASD in adults is unclear. METHOD: We studied 476 adults, seen consecutively at a national ASD diagnostic referral service for suspected ASD. We tested AQ scores as predictors of ASD diagnosis made by expert clinicians according to International Classification of Diseases (ICD)-10 criteria, informed by the Autism Diagnostic Observation Schedule-Generic (ADOS-G) and Autism Diagnostic Interview-Revised (ADI-R) assessments. RESULTS: Of the participants, 73% received a clinical diagnosis of ASD. Self-report AQ scores did not significantly predict receipt of a diagnosis. While AQ scores provided high sensitivity of 0.77 [95% confidence interval (CI) 0.72-0.82] and positive predictive value of 0.76 (95% CI 0.70-0.80), the specificity of 0.29 (95% CI 0.20 0.38) and negative predictive value of 0.36 (95% CI 0.22-0.40) were low. Thus, 64% of those who scored below the AQ cut-off were 'false negatives' who did in fact have ASD. Co-morbidity data revealed that generalized anxiety disorder may 'mimic' ASD and inflate AQ scores, leading to false positives. CONCLUSIONS: The AQ's utility for screening referrals was limited in this sample. Recommendations supporting the AQ's role in the assessment of adult ASD, e.g. UK NICE guidelines, may need to be reconsidered. PMID- 27353454 TI - Solvent-dependent fluorescent-colorimetric probe for dual monitoring of Al(3+) and Cu(2+) in aqueous solution: an application to bio-imaging. AB - A novel, quinoline-based smart probe L has been designed for the detection of Al(3+) and Cu(2+) at physiological range. The unprecedented solvent-dependent sensitivities of the probe L for simultaneous detection of Al(3+) and Cu(2+) ions with high selectivity and sensitivity have been observed for the first time. It displays quick responses through visible colorimetric as well as fluorogenic changes towards both Al(3+) and Cu(2+), as delineated by absorption and fluorescence titrations. The sensitivity of the fluorescence-based assay (12.6 nM) for Al(3+) and (18.4 nM) for Cu(2+) is far below the limit recommended in the World Health Organization (WHO) guidelines for drinking water. From (1)H NMR data, the Job plot and the ESI-MS spectrum, 1 : 2 stoichiometric complexations between L and both metals have been established. The geometry and spectral property of L and its metal complexes have been well rationalized by DFT calculations. This probe L has been tested as being highly suitable for mapping Al(3+) and Cu(2+) in human breast cancer cells, MCF7, thus providing a wonderful candidate for tracking Al(3+) and Cu(2+) in biological organisms and processes. The proposed chemosensor L has also been successfully applied for analysis of real samples. PMID- 27353456 TI - General anaesthesia vs. conscious sedation for transfemoral aortic valve implantation: a single UK centre before-and-after study. AB - Reported data suggest that 99% of transfemoral, transcatheter aortic valve implantations in the UK are performed under general anaesthesia. This before-and after study is the first UK comparison of conscious sedation vs. general anaesthesia for this procedure. Patients who underwent general anaesthesia received tracheal intubation, positive pressure ventilation, radial arterial and central venous access and urinary catheterisation. Anaesthesia was maintained with propofol or sevoflurane. Patients who received conscious sedation had a fascia iliaca and ilioinguinal nerve block and low-dose remifentanil infusion, without invasive monitoring or urinary catheterisation. Recruitment took place between August 2012 and July 2015, with a 6-month crossover period between November 2013 and June 2014. A total of 88 patients were analysed, evenly divided between the two groups. Patients receiving conscious sedation had a shorter anaesthetic time (mean (SD) 121 (28) min vs. 145 (41) min; p < 0.001) and recovery room time (110 (50) min vs. 155 (48) min; p = 0.001), lower requirement for inotropes (4.6% vs 81.8%; OR (95% CI) 0.1 (0.002-0.050); p < 0.001) and a lower incidence of malignant dysrhythmia (0% vs 11.4%; p = 0.020). Conscious sedation appears a feasible alternative to general anaesthesia for this procedure and is associated with a reduced requirement for inotropic support and improved efficiency. PMID- 27353455 TI - Pennsylvania's Medical Home Initiative: Reductions in Healthcare Utilization and Cost Among Medicaid Patients with Medicaland Psychiatric Comorbidities. AB - BACKGROUND: The Chronic Care Initiative (CCI) was a large state-wide patient centered medical home (PCMH) initiative in Pennsylvania in place from 2008-2011. OBJECTIVE: Determine whether the CCI impacted the utilization and costs for Medicaid patients with chronic medical conditions and comorbid psychiatric or substance use disorders. DESIGN: Analysis of Medicaid claims using difference-in difference regression analyses to compare changes in utilization and costs for patients treated at CCI practices to propensity score-matched patients treated at comparison non-CCI practices. SETTING: Ninety-six CCI practices in Pennsylvania and 60 non-CCI practices during the same time period. PARTICIPANTS: A total of 11,105 comorbid Medicaid patients treated in CCI practices and an equal number of propensity-matched comparison patients treated in non-CCI practices. MEASUREMENTS: Changes in total per-patient costs from 1 year prior to 1 year following an index episode period. Secondary outcomes included utilization and costs for emergency department (ED), inpatient, and outpatient services. RESULTS: The CCI group experienced an average adjusted total cost savings of $4145.28 per patient per year (P = 0.023) for the CCI relative to the non-CCI group. This was largely driven by a $3521.15 savings (P = 0.046) in inpatient medical costs, in addition to relative savings in outpatient psychiatric ($21.54, P < 0.001) and substance abuse service costs ($16.42, P = 0.013), compared to the non-CCI group. The CCI group, related to the non-CCI group, had decreases in expected mean counts of ED visits (for those who had any) and psychiatric hospitalizations of 15.6 (95 % CI: -21, -9) and 40.7 (95 % CI: -57, -18) percentage points respectively. LIMITATIONS: We do not measure quality of care and cannot make conclusions about the overall cost-effectiveness or long-term effects of the CCI. CONCLUSIONS: The CCI was associated with substantial cost savings, attributable primarily to reduced inpatient costs, among a high-risk group of Medicaid patients, who may disproportionally benefit from care management in patient centered medical homes. PMID- 27353457 TI - GATA1 mutations in a cohort of Malaysian children with Down syndrome-associated myeloid disorder. AB - INTRODUCTION: Children with Down syndrome (DS) are at increased risk of developing distinctive clonal myeloid disorders, including transient abnormal myelopoiesis (TAM) and myeloid leukaemia of DS (ML-DS). TAM connotes a spontaneously resolving congenital myeloproliferative state observed in 10%-20% of DS newborns. Following varying intervals of apparent remission, a proportion of children with TAM progress to develop ML-DS in early childhood. Therefore, TAM and ML-DS represent a biological continuum. Both disorders are characterised by recurring truncating somatic mutations of the GATA1 gene, which are considered key pathogenetic events. METHODS: We herein report, to our knowledge, the first observation on the frequency and nature of GATA1 gene mutations in a cohort of Malaysian children with DS-associated TAM (n = 9) and ML-DS (n = 24) encountered successively over a period of five years at a national referral centre. RESULTS: Of the 29 patients who underwent GATA1 analysis, GATA1 mutations were observed in 15 (51.7%) patients, including 6 (75.0%) out of 8 patients with TAM, and 9 (42.9%) of 21 patients with ML-DS. All identified mutations were located in exon 2 and the majority were sequence-terminating insertions or deletions (66.7%), including several hitherto unreported mutations (12 out of 15). CONCLUSION: The low frequency of GATA1 mutations in ML-DS patients is unusual and potentially indicates distinctive genomic events in our patient cohort. PMID- 27353458 TI - Osteopontin deficiency reduces kidney damage from hypercholesterolemia in Apolipoprotein E-deficient mice. AB - Hypercholesterolemia is a well-established risk factor for kidney injury, which can lead to chronic kidney disease (CKD). Osteopontin (OPN) has been implicated in the pathology of several renal conditions. This study was to evaluate the effects of OPN on hypercholesterolemia induced renal dysfunction. Eight-week-old male mice were divided into 4 groups: apolipoprotein E knockout (ApoE(-/-)) and ApoE/OPN knockout (ApoE(-/-)/OPN(-/-)) mice fed a normal diet (ND) or high cholesterol diet (HD). After 4 weeks, Periodic acid-Schiff (PAS) and oil red O staining revealed excessive lipid deposition in the glomeruli of ApoE(-/-)HD mice, however, significantly suppressed in ApoE(-/-)/OPN(-/-)HD mice. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression was lower in the glomeruli of ApoE(-/-)/OPN(-/-)HD mice than ApoE(-/-)HD mice. In vitro study, primary mesangial cells were incubated with recombinant mouse OPN (rmOPN). RmOPN induced LOX-1 mRNA and protein expression in primary mesangial cells. Pre treatment with an ERK inhibitor suppressed the LOX-1 gene expression induced by rmOPN. These results indicate that OPN contributes to kidney damage in hypercholesterolemia and suggest that inhibition of OPN may provide a potential therapeutic target for the prevention of hypercholesterolemia. PMID- 27353459 TI - Effectiveness of vildagliptin versus other oral antidiabetes drugs as add-on to sulphonylurea monotherapy: Post hoc analysis from the EDGE study. AB - AIM: In this post hoc analysis of the EDGE study, we assessed the effectiveness and safety of vildagliptin versus other oral antidiabetes drugs (OADs) as add-on to first-line sulphonylurea (SU) therapy in patients who did not receive metformin in a real-life setting. METHODS: The primary endpoint was odds of achieving an HbA1c reduction of >0.3% without tolerability issues. Secondary endpoint was odds of achieving HbA1c <7.0% without hypoglycaemia or weight gain. Changes in HbA1c, body weight; and safety were also assessed. RESULTS: 2936 patients received vildagliptin and 820 received comparator OADs (any alpha-GI, TZD, glinide) as add-on to first-line SU therapy. Overall, the mean age, disease duration, HbA1c, and BMI at baseline were 57.1 years, 6.3 years, 8.5%, and 27.7kg/m2, respectively. The odds ratios for achieving primary and secondary endpoints were 1.6 (95% CI: 1.36, 1.86; p<0.0001) and 1.8 (1.45, 2.21; p<0.0001), respectively, in favour of vildagliptin. The between-treatment differences (vildagliptin vs. comparator OAD) for the mean change in HbA1c and body weight were -0.2+/-0.04% (p<0.0001) and -0.8+/-0.16kg (p<0.0001), respectively. Overall, the incidence of adverse events was low (vildagliptin, 7% vs. comparator, 8.2%) in both groups. Similar results were observed in a subset of patients enrolled from India and patients who received TZDs as a comparator OAD. CONCLUSION: Under real-life settings, vildagliptin as add-on to SU monotherapy showed better glycaemic response without tolerability issues compared with other OADs. PMID- 27353460 TI - Hepatic radioembolization from transradial access: initial experience and comparison to transfemoral access. AB - PURPOSE: Despite the growing evidence in the cardiology literature that transradial approach has substantial benefits over transfemoral access, this technique is rarely used during interventions in the systemic circulation. The aim of this study was to evaluate the feasibility of transradial approach for hepatic radioembolization and to compare it with transfemoral approach. METHODS: Sixty-four hepatic radioembolizations performed in 50 patients were included in the study. Thirty-three procedures were performed via radial access in 27 patients, and 31 procedures were performed via femoral access in 23 patients. RESULTS: There was 100% technical success in performing hepatic radioembolization in both groups. The majority (97%) of the patients who underwent transradial radioembolization reported preference for radial artery access. The fluoroscopy time was significantly longer (9.45+/-5.09 min vs. 5.72+/-3.67 min, P < 0.01) and the radiation dose was significantly higher (597.8+/-585.2 mGy vs. 302.8+/-208.3 mGy, P < 0.01) in the radial group compared with the femoral group. The direct cost savings using radial access versus femoral access is approximately $100/procedure. In addition, there was a one hour (50%) shorter postprocedural stay for patients who underwent the transradial procedure. CONCLUSION: Transradial access is feasible for hepatic radioembolization. The transradial approach is cheaper and offers improved patient comfort. However, it is technically challenging, with longer fluoroscopy times and higher radiation doses. Transradial approach should be considered as a primary choice in patients with low platelet count and/or morbid obesity. Transradial access should be in the procedural repertoire of every interventional radiologist. PMID- 27353461 TI - An evolutionarily conserved allosteric site modulates beta-lactamase activity. AB - Declining efficiency of antibiotic-inhibitor combinatorial therapies in treating beta-lactamase mediated resistance necessitates novel inhibitor development. Allosteric inhibition offers an alternative to conventional drugs that target the conserved active site. Here, we show that the evolutionarily conserved PWP triad located at the N-terminus of the H10 helix directly interacts with the allosteric site in TEM-1 beta-lactamase and regulates its activity. While point mutations in the PWP triad preserve the overall secondary structures around the allosteric site, they result in a more open and dynamic global structure with decreased chemical stability and increased aggregation propensity. These mutant enzymes with a less compact hydrophobic core around the allosteric site displayed significant activity loss. Detailed sequence and structure conservation analyses revealed that the PWP triad is an evolutionarily conserved motif unique to class A beta-lactamases aligning its allosteric site and hence is an effective potential target for enzyme regulation and selective drug design. PMID- 27353462 TI - Sexual dimorphism in the glucose homeostasis phenotype of the Aromatase Knockout (ArKO) mice. AB - We investigated the effects of estrogens on glucose homeostasis using the Aromatase Knockout (ArKO) mouse, which is unable to convert androgens into estrogens. The ArKO mouse is a model of total estrogen ablation which develops symptoms of metabolic syndrome. To determine the development and progression of whole body state of insulin resistance of ArKO mice, comprehensive whole body tolerance tests were performed on WT, ArKO and estrogen administrated mice at 3 and 12 months of age. The absence of estrogens in the male ArKO mice leads to hepatic insulin resistance, glucose and pyruvate intolerance from 3 to 12 months with consistent improvement upon estrogen treatment. Estrogen absence in the female ArKO mice leads to glucose intolerance without pyruvate intolerance or insulin resistance. The replacement of estrogens in the female WT and ArKO mice exhibited both insulin sensitizing and resistance effects depending on age and dosage. In conclusion, this study presents information on the sexually dimorphic roles of estrogens on glucose homeostasis regulation. PMID- 27353463 TI - Resistin impairs glucose permeability in EA.hy926 cells by down-regulating GLUT1 expression. AB - Type 2 diabetes mellitus (T2DM) is a chronic disease which is now affecting the health of more and more people in the world. Resistin, discovered in 2001, is considered to be closely related to metabolic dysfunction and obesity. Previous study showed that hyperglycemia is always accompanied by a high serum resistin concentration. We therefore investigated whether resistin can mediate glucose transfer across the blood-tissue barrier. Here, we employed a transwell system to analyze glucose permeability in EA.hy926 human endothelial cells treated without or with human resistin. In EA.hy926 cells treated with resistin, the permeability to glucose was heavily impaired. This was due to the down-regulation of GLUT1 expression as a result of the treatment, rather than regulation of tight junctions. In addition, overexpression of GLUT1 in EA.hy926 cells was able to recover the blocking effect of resistin on glucose permeability. We further found that resistin could inhibit the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and consequently impede the transcription of GLUT1. The results of the present study suggested that resistin could cause glucose retention in serum and thus result in hyperglycemia. This provides a novel explanation for hyperglycemia and a potential new way of treating type 2 diabetes mellitus. PMID- 27353464 TI - Rise and fall of KPC-producing Klebsiella pneumoniae in New York City. AB - OBJECTIVES: The study objective was to examine the epidemiological trends of KPC producing Klebsiella pneumoniae in New York City medical centres. PATIENTS AND METHODS: Single patient isolates of K. pneumoniae were collected from nine medical centres in New York City during a 3 month period from 2013 to 2014. Isolates were tested for the presence of blaKPC. Results were compared with similar surveillance studies conducted in 2006 and 2009. Infection control data, including utilization of medical devices, were analysed at a subset of hospitals. RESULTS: There was a progressive decline in the percentage of K. pneumoniae harbouring blaKPC from 2006 to 2013-14. For the nine hospitals that participated in all three surveillance studies, the percentages of isolates with blaKPC fell from 36% in 2006 to 25% in 2009 to 13% in 2013-14. Seven of the nine hospitals had marked declines in isolates with blaKPC, while two hospitals continued to struggle with this pathogen. These two hospitals were smaller and had longer lengths of patient stay. Device utilization rates were obtained from two hospitals that successfully controlled the spread of KPC-producing K. pneumoniae; both had ~20%-25% reduction in the usage of urinary catheters. Changes in antibiotic usage at one hospital could not explain the decline in these pathogens. CONCLUSIONS: Over the past decade there has been a steady decline in KPC-producing K. pneumoniae in most New York City hospitals. The reason for the decline is probably multifactorial, involving a reduction in device (catheter) utilization and possibly an improvement in infection control practices. PMID- 27353465 TI - In vitro biological evaluation of novel broad-spectrum isothiazolone inhibitors of bacterial type II topoisomerases. AB - OBJECTIVES: To evaluate the in vitro biological properties of a novel class of isothiazolone inhibitors of the bacterial type II topoisomerases. METHODS: Inhibition of DNA gyrase and topoisomerase IV activity was assessed using DNA supercoiling and decatenation assays. MIC and MBC were determined according to CLSI guidelines. Antibacterial combinations were assessed using a two-dimensional chequerboard MIC method. Spontaneous frequency of resistance was measured at various multiples of the MIC. Resistant mutants were generated by serial passage at subinhibitory concentrations of antibacterials and genetic mutations were determined through whole genome sequencing. Mammalian cytotoxicity was evaluated using the HepG2 cell line. RESULTS: Representative isothiazolone compound REDX04957 and its enantiomers (REDX05967 and REDX05990) showed broad-spectrum bactericidal activity against the ESKAPE organisms, with the exception of Enterococcus spp., as well as against a variety of other human bacterial pathogens. Compounds retained activity against quinolone-resistant strains harbouring GyrA S83L and D87G mutations (MIC <=4 mg/L). Compounds inhibited the supercoiling activity of wild-type DNA gyrase and the decatenation function of topoisomerase IV. Frequency of resistance of REDX04957 at 4* MIC was <9.1 * 10( 9). Against a panel of recent MDR isolates, REDX05967 demonstrated activity against Acinetobacter baumannii with MIC50 and MIC90 of 16 and 64 mg/L, respectively. Compounds showed a lack of cytotoxicity against HepG2 cells at 128 mg/L. CONCLUSIONS: Isothiazolone compounds show potent activity against Gram positive and -negative pathogens with a dual targeting mechanism-of-action and a low potential for resistance development, meriting their continued investigation as broad-spectrum antibacterial agents. PMID- 27353466 TI - Impact of amoxicillin therapy on resistance selection in patients with community acquired lower respiratory tract infections: a randomized, placebo-controlled study. AB - OBJECTIVES: To determine the effect of amoxicillin treatment on resistance selection in patients with community-acquired lower respiratory tract infections in a randomized, placebo-controlled trial. METHODS: Patients were prescribed amoxicillin 1 g, three times daily (n = 52) or placebo (n = 50) for 7 days. Oropharyngeal swabs obtained before, within 48 h post-treatment and at 28-35 days were assessed for proportions of amoxicillin-resistant (ARS; amoxicillin MIC >=2 mg/L) and -non-susceptible (ANS; MIC >=0.5 mg/L) streptococci. Alterations in amoxicillin MICs and in penicillin-binding-proteins were also investigated. ITT and PP analyses were conducted. RESULTS: ARS and ANS proportions increased 11- and 2.5-fold, respectively, within 48 h post-amoxicillin treatment compared with placebo [ARS mean increase (MI) 9.46, 95% CI 5.57-13.35; ANS MI 39.87, 95% CI 30.96-48.78; P < 0.0001 for both]. However, these differences were no longer significant at days 28-35 (ARS MI -3.06, 95% CI -7.34 to 1.21; ANS MI 4.91, 95% CI -4.79 to 14.62; P > 0.1588). ARS/ANS were grouped by pbp mutations. Group 1 strains exhibited significantly lower amoxicillin resistance (mean MIC 2.8 mg/L, 95% CI 2.6-3.1) than group 2 (mean MIC 9.3 mg/L, 95% CI 8.1-10.5; P < 0.0001). Group 2 strains predominated immediately post-treatment (61.07%) and although decreased by days 28-35 (30.71%), proportions remained higher than baseline (18.70%; P = 0.0004). CONCLUSIONS: By utilizing oropharyngeal streptococci as model organisms this study provides the first prospective, experimental evidence that resistance selection in patients receiving amoxicillin is modest and short lived, probably due to 'fitness costs' engendered by high-level resistance conferring mutations. This evidence further supports European guidelines that recommend amoxicillin when an antibiotic is indicated for community-acquired lower respiratory tract infections. PMID- 27353467 TI - Comparative efficacy of telavancin and daptomycin in experimental endocarditis due to multi-clonotype MRSA strains. AB - BACKGROUND: MRSA strains of clonal complexes (CCs) 5, 8, 30 and 45 are leading causes of complicated endovascular infections associated with suboptimal clinical outcomes. Telavancin is a novel anti-MRSA agent that both inhibits bacterial cell wall synthesis and disrupts membranes by depolarization. METHODS: In this study, we compared the in vitro susceptibility and in vivo efficacy of telavancin versus daptomycin in an experimental rabbit infective endocarditis (IE) model caused by four MRSA strains representing each of the above CC types. RESULTS: All study strains were susceptible to telavancin (MICs of <=0.12 mg/L) and daptomycin (MICs of <=0.5 mg/L). In vitro time-kill analyses revealed that supra-MIC levels of telavancin were effective at preventing regrowth at 24 h of incubation. In the IE animal model for all CC types, treatment with telavancin produced significantly greater reductions in MRSA counts as compared with daptomycin-treated animals in all target tissues. Moreover, telavancin-treated animals had a significantly higher percentage of sterile tissue cultures versus daptomycin-treated animals (e.g. 78%-100% versus 0% sterile vegetations and 100% versus 0%-11% sterile kidneys and spleen, in the telavancin- and daptomycin-treated animals, respectively). CONCLUSIONS: These results suggest that telavancin exhibits significantly greater efficacies versus daptomycin in treating experimental IE caused by MRSA clinical isolates across four common CC types. PMID- 27353468 TI - Development and validation of the knowledge and attitudes regarding antibiotics and resistance (KAAR-11) questionnaire for primary care physicians. AB - OBJECTIVES: The aim of this study was to develop a novel, self-administered questionnaire to identify primary-care physicians' knowledge and attitudes regarding antibiotics and resistance (KAAR). METHODS: The study population comprised primary care physicians. The study was conducted in five phases. Phase I consisted of a systematic review and qualitative focus-group study (n = 33 physicians), in which items were formulated so as to be measured on a continuous, visual analogue scale (VAS); in Phase II, content validation and face validity were evaluated by a panel of experts, which reformulated, added and deleted items; Phase III consisted of a pilot study on a population possessing similar characteristics (n = 15); in Phase IV, we analysed reliability by means of a test retest study (n = 91) and calculated the intraclass correlation coefficients (ICCs); and in Phase V, we assessed construct validity by applying the known groups technique, measuring the differences between contrasting groups of physicians formed according to antibiotic prescription quality indicators (group 1, n = 156 versus group 2, n = 191). RESULTS: Following Phases I and II, the questionnaire contained 16 knowledge and attitude items. Participants in the pilot study (Phase III) reported no difficulty. The test-retest study (Phase IV) showed that 11 of the 16 initial knowledge and attitude items yielded an ICC > 0.5, while analysis of known-groups validity (Phase V) showed that 13 of the 16 initial items which assessed knowledge and attitudes discriminated between physicians with good and bad indicators of antibiotics prescription. CONCLUSION: The final 11 item KAAR questionnaire appears to be valid, reliable and responsive. PMID- 27353469 TI - Sequential steps of daptomycin resistance in Enterococcus faecium and reversion to hypersusceptibility through IS-mediated inactivation of the liaFSR operon. AB - OBJECTIVES: To improve understanding of mechanisms of daptomycin resistance and to dissect the genetic basis of reversion to daptomycin hypersusceptibility in Enterococcus faecium. METHODS: Daptomycin-resistant mutants (Mut4, Mut8, Mut16, Mut32, Mut64 and Mut128 with MICs from 4 to 128 mg/L) were obtained in vitro from E. faecium strain Aus0004 (MIC at 2 mg/L). The entire genome sequences of Mut64 and Mut128 were determined as well as those of liaFSR and cls genes for other mutants and corresponding revertants (named Rev4 to Rev128). The study of daptomycin resistance stability was performed without any selective pressure. The expression of liaF, liaS and liaR genes was quantified by quantitative RT-PCR. RESULTS: By comparative genomic analysis, substitutions Asn13Ser in cls and Gly92Asp in liaS were identified in Mut64 and Mut128. Only the liaS mutation was found in Mut16 and Mut32 while Mut4 and Mut8 were devoid of any mutation. After 15 days, all mutants except Mut4 reverted to daptomycin hypersusceptibility (MICs from 0.12 to 0.25 mg/L). In all revertants (except Rev4 and Rev8), an IS was found in the liaFSR operon with a dramatic decrease of its expression: IS66 in the promoter region of liaF (Rev16 and Rev64), IS30 in liaR (Rev32) and IS982 in liaF (Rev128). CONCLUSIONS: We demonstrated the stepwise and sequential acquisition of mutations in liaS and in cls leading to daptomycin resistance in E. faecium, and the instability of daptomycin resistance as well as the role of liaFSR inactivation in reversion to daptomycin hypersusceptibility. PMID- 27353470 TI - Antimicrobial resistance surveillance in urinary tract infections in primary care. AB - Urinary tract infection (UTI) is one of the most common reasons for prescription of antimicrobials in primary care. Laboratory resistance data produced because of specimen analysis to support individual patient diagnosis and management are generalized to guide empirical therapy across a wider population, but are limited by bias toward certain patient groups and almost certainly overestimate the incidence of resistance. Other methods of surveillance are required to provide unbiased estimates of antimicrobial resistance, but need to be sustainable. Sentinel surveillance, perineal flora sampling and development of clinical algorithms to support more stratified and personalized antimicrobial prescribing need to be further investigated. Linkages to prescription and clinical outcome data are essential if the burden of antimicrobial resistance in UTI is to be understood. Pilot and feasibility studies need to be performed to establish the best approach to enhancing the quality, relevance and sustainability of antimicrobial resistance surveillance in community-acquired UTI. PMID- 27353471 TI - Synovial sarcoma cell lines showed reduced DNA repair activity and sensitivity to a PARP inhibitor. AB - Synovial sarcoma is a soft-tissue sarcoma and a rare type of cancer. Unfortunately, effective chemotherapies for synovial sarcomas have not been established. In this report, we show that synovial sarcoma cell lines have reduced repair activity for DNA damage induced by ionizing radiation (IR) and a topoisomerase II inhibitor (etoposide). We also observed reduced recruitment of RAD51 homologue (S. cerevisiae; RAD51) at sites of double-strand breaks (DSBs) in synovial sarcoma cell lines that had been exposed to IR. These findings showed that synovial sarcoma cell lines are defective in homologous recombination (HR) repair. Furthermore, we found that a poly-(ADP-ribose) polymerase (PARP) inhibitor (AZD2281; olaparib) effectively reduced the growth of synovial sarcoma cell lines in the presence of an alkylating agent (temozolomide). Our findings offer evidence that treatment combining a PARP inhibitor and an alkylating agent could have therapeutic benefits in the treatment of synovial sarcoma. PMID- 27353472 TI - An atypical forkhead-containing transcription factor SsFKH1 is involved in sclerotial formation and is essential for pathogenicity in Sclerotinia sclerotiorum. AB - Sclerotinia sclerotiorum (Lib.) de Bary is a necrotrophic plant pathogen with a worldwide distribution. The sclerotia of S. sclerotiorum are pigmented multicellular structures formed from the aggregation of vegetative hyphae. These survival structures play a central role in the life and infection cycles of this pathogen. Here, we characterized an atypical forkhead (FKH)-box-containing protein, SsFKH1, involved in sclerotial development and virulence. To investigate the role of SsFkh1 in S. sclerotiorum, the partial sequence of SsFkh1 was cloned and RNA interference (RNAi)-based gene silencing was employed to alter the expression of SsFkh1. RNA-silenced mutants with significantly reduced SsFkh1 RNA levels exhibited slow hyphal growth and sclerotial developmental defects. In addition, the expression levels of a set of putative melanin biosynthesis-related laccase genes and a polyketide synthase-encoding gene were significantly down regulated in silenced strains. Disease assays demonstrated that pathogenicity in RNAi-silenced strains was significantly compromised with the development of a smaller infection lesion on tomato leaves. Collectively, the results suggest that SsFkh1 is involved in hyphal growth, virulence and sclerotial formation in S. sclerotiorum. PMID- 27353473 TI - Response to 5-azacytidine in a patient with TET2-mutated angioimmunoblastic T cell lymphoma and chronic myelomonocytic leukaemia preceded by an EBV-positive large B-cell lymphoma. AB - We report the case of a patient with a history of Epstein-Barr virus-positive large B-cell lymphoma, who relapsed with an angioimmunoblastic T-cell lymphoma (AITL) associated with a chronic myelomonocytic leukaemia (CMML). We performed targeted next-generation sequencing on CMML and AITL DNA, which revealed mutations of TET2, DNMT3A, SRSF2, NRAS and IDH1, thus confirming that the spectrum of AITL mutations share similarities with myeloid disorders. The frequencies of TET2/DNMT3A and SRSF2 variants could support the hypothesis that TET2/DNMT3A mutations occurred in an early progenitor cell, which later progressed to both the AITL and CMML clones. Treatment with 5-azacytidine led to the complete remission of both diseases. Thus, targeting DNA methylation abnormalities in AITL may be an alternative strategy to chemotherapy. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27353474 TI - Expression of Bcl-2 genes in channel catfish after bacterial infection and hypoxia stress. AB - Bcl-2 proteins are of vital importance in regulation of apoptosis, and are involved in a number of biological processes such as carcinogenesis and immune responses. Bcl-2 genes have been well studied in mammals, while they are not well investigated in teleost fish including channel catfish, the major aquaculture species in the United States. In this study, we identified 34 bcl-2 genes from the channel catfish genome, and verified their identities by conducting phylogenetic and syntenic analyses. The expression profiles of the bcl-2 genes in response to bacterial infections (Edwardsiella ictaluri and Flavobacterium columnare) and hypoxia stress were determined by performing meta-analysis using the existing RNA-Seq datasets. Differential expressions of bcl-2 genes were observed after bacterial infections and hypoxia treatment, including 22 bcl-2 genes after E. ictaluri infection, 22 bcl-2 genes after F. columnare infection, and 19 bcl-2 genes after hypoxia stress. Overall, the expression of the pro apoptotic bcl-2 genes were repressed after bacterial infection and hypoxia stress, indicating that bcl-2 genes are potentially involved in the stress response by reducing cell apoptosis. Some bcl-2 genes, such as bcl2b, mcl1a, bmf1, and bnip3, showed different expression pattern during the E. ictaluri and F. columnare infection, suggesting the difference in the pathogenicity of diseases. This work presented the first systematic identification and annotation of bcl-2 genes in catfish, providing essential genomic resources for further immune and physiological studies. PMID- 27353475 TI - Nurses' oral hygiene care practices with hospitalised older adults in postacute settings. AB - AIM AND OBJECTIVE: The purpose of this study was to explore how nurses provide bedtime oral hygiene care, how they decide on interventions provided, and what factors influence their ability to provide oral care. BACKGROUND: Current evidence links poor oral hygiene to systemic and infectious diseases such as pneumonia. Hospitalised patients, who now retain their teeth into older adulthood, often rely on nurses to provide oral hygiene care. Nurses have the potential to impact oral health outcomes and quality of life by controlling plaque. However, oral hygiene care practices of nurses in postacute hospital settings are relatively unknown. DESIGN: A qualitative, exploratory multiple-case study was conducted with 25 nurses working on five inpatient units at different hospitals. METHODS: Nurses were accompanied on their evening rounds to observe oral care practices, the physical environment and workflow. Thematic analysis was used to analyse the case study data including transcripts of guided conversations, field notes and documents. Within-case analysis was followed by cross-case analysis. RESULTS: Findings indicate that (i) nurses often convey oral hygiene care to their patients as being optional; (ii) nurses are inclined to preserve patient autonomy in oral hygiene care; (iii) oral hygiene care is often spontaneous and variable, and may not be informed by evidence; and (iv) oral hygiene care is not embedded into bedtime care routines. CONCLUSIONS: Oral hygiene care is discretionary and often missed care. IMPLICATIONS FOR PRACTICE: Nurses need knowledge of the health benefits of oral care, and skills related to assessment and approaches to oral care. Availability of effective products and supplies facilitates provision of oral care. The evidence for oral hygiene care practices, outcomes of nurse-administered oral care and nursing's role in influencing the oral health literacy of patients require further study. PMID- 27353476 TI - Feedback control of Campylobacter jejuni flagellin levels through reciprocal binding of FliW to flagellin and the global regulator CsrA. AB - Bacterial flagella assembly is tightly regulated to ensure a timely and sequential production of the various flagellum constituents. In the pathogen Campylobacter jejuni the hierarchy in flagella biosynthesis is largely determined at the transcriptional level through the activity of the alternative sigma factors sigma54 and sigma28 . Here, we report that C. jejuni flagellin levels are also controlled at the post-transcriptional level via the thus far poorly characterized flagellar assembly factor FliW. Analysis of flagellin synthesis in C. jejuni 81116 and a DeltafliW knock-out mutant showed reduced flagellin protein levels in the mutant strain while ectopic expression of FliW resulted in enhanced levels. Real-time RT-PCR revealed relatively minor changes in flaA and flaB mRNA levels for the recombinant and parent strain consistent with post-transcriptional regulation. Purified FliW was found to bind to FlaA and FlaB flagellin as well as to the global post-transcriptional regulator CsrA. Inactivation of CsrA resulted in increased levels of flagellin translation. An in vitro translation assay confirmed the regulatory role of CsrA in flagellin biosynthesis. We propose that competitive reciprocal binding of FliW to flagellins and the RNA binding protein CsrA serves as a feedback mechanism to control the number of cytosolic flagellin copies at the protein level. PMID- 27353477 TI - DNA replication and beyond. PMID- 27353478 TI - Tight junctions: from simple barriers to multifunctional molecular gates. AB - Epithelia and endothelia separate different tissue compartments and protect multicellular organisms from the outside world. This requires the formation of tight junctions, selective gates that control paracellular diffusion of ions and solutes. Tight junctions also form the border between the apical and basolateral plasma-membrane domains and are linked to the machinery that controls apicobasal polarization. Additionally, signalling networks that guide diverse cell behaviours and functions are connected to tight junctions, transmitting information to and from the cytoskeleton, nucleus and different cell adhesion complexes. Recent advances have broadened our understanding of the molecular architecture and cellular functions of tight junctions. PMID- 27353480 TI - Glycogen distribution in the microwave-fixed mouse brain reveals heterogeneous astrocytic patterns. AB - In the brain, glycogen metabolism has been implied in synaptic plasticity and learning, yet the distribution of this molecule has not been fully described. We investigated cerebral glycogen of the mouse by immunohistochemistry (IHC) using two monoclonal antibodies that have different affinities depending on the glycogen size. The use of focused microwave irradiation yielded well-defined glycogen immunoreactive signals compared with the conventional periodic acid Schiff method. The IHC signals displayed a punctate distribution localized predominantly in astrocytic processes. Glycogen immunoreactivity (IR) was high in the hippocampus, striatum, cortex, and cerebellar molecular layer, whereas it was low in the white matter and most of the subcortical structures. Additionally, glycogen distribution in the hippocampal CA3-CA1 and striatum had a 'patchy' appearance with glycogen-rich and glycogen-poor astrocytes appearing in alternation. The glycogen patches were more evident with large-molecule glycogen in young adult mice but they were hardly observable in aged mice (1-2 years old). Our results reveal brain region-dependent glycogen accumulation and possibly metabolic heterogeneity of astrocytes. GLIA 2016;64:1532-1545. PMID- 27353481 TI - The 5th world symposium for lymphedema surgery-Recent updates in lymphedema surgery and setting up of a global knowledge exchange platform. AB - The successful completion of the 5th World Symposium for Lymphedema Surgery (WSLS) marks another milestone in the development and advancement of the management of lymphedema. We present our experience in organizing such a scientific lymphedema conference as well as a summary of seven variable live surgeries used for treating lymphedema. An update of current knowledge and determination of future direction in the treatment of lymphedema was made possible via WSLS 2016. J. Surg. Oncol. 2017;115:6-12. (c) 2016 Wiley Periodicals, Inc. PMID- 27353479 TI - Coupling changes in cell shape to chromosome segregation. AB - Animal cells undergo dramatic changes in shape, mechanics and polarity as they progress through the different stages of cell division. These changes begin at mitotic entry, with cell-substrate adhesion remodelling, assembly of a cortical actomyosin network and osmotic swelling, which together enable cells to adopt a near spherical form even when growing in a crowded tissue environment. These shape changes, which probably aid spindle assembly and positioning, are then reversed at mitotic exit to restore the interphase cell morphology. Here, we discuss the dynamics, regulation and function of these processes, and how cell shape changes and sister chromatid segregation are coupled to ensure that the daughter cells generated through division receive their fair inheritance. PMID- 27353482 TI - Cancer Recurrence After Esophagectomy: Impact of Postoperative Infection in Propensity-Matched Cohorts. AB - BACKGROUND: Postoperative infection increases cancer recurrence and worsens survival in colorectal cancer, but the relationship for esophagogastric adenocarcinoma after esophagectomy is not well defined. We aimed to determine whether recurrence and survival after minimally invasive esophagectomy for esophagogastric adenocarcinoma were influenced by postoperative infection using propensity-matched analysis. METHODS: We abstracted data for 810 patients (1997 2010) and defined exposure as at least 1 in-hospital or 30-day infectious complication (n = 206 [25%]). Using 29 pretreatment/intraoperative variables, patients were propensity-score matched (caliper = 0.05). Time to cancer recurrence and survival (Kaplan-Meier curves and the Breslow test), and associated factors (Cox regression with shared frailty) were assessed. RESULTS: After propensity matching (n = 167 pairs), median bias across propensity-score variables was reduced from 12.9% (p < 0.001) to 4.4% (p = 1.000). Postoperative infection was not associated with rate (n = 60 versus 63; McNemar p = 0.736) or time to recurrence in those in whom disease recurred (median, 10.7 versus 11.1 months; Wilcoxon signed-rank p = 0.455) but was associated with shorter overall survival (n = 124 versus 102 deaths; median, 26 versus 41 months; Breslow p = 0.002). After adjusting for age, body mass index, neoadjuvant therapy, sex, comorbidity score, positive resection margins, pathologic stage, R0 resection, and recurrence, postoperative infection was associated with a 44% greater hazard for death (hazard ratio, 1.44; 95% confidence interval, 1.10-1.89). CONCLUSIONS: In patients with esophagogastric adenocarcinoma, infections after esophagectomy were not associated with an increased rate or earlier time to recurrence when baseline characteristics associated with infection risk were balanced using propensity-score matching. Despite this, overall survival was shorter in patients with infectious complications. After adjusting for other important survival predictors, infections after esophagectomy continued to be independently associated with worse survival. PMID- 27353483 TI - Recurrent Coarctation After Neonatal Univentricular and Biventricular Norwood Type Arch Reconstruction. AB - BACKGROUND: Previous studies have evaluated recurrent coarctation after the Norwood procedure (NP) in patients with single-ventricle (SV) anatomy. Extended patch augmentation of the aorta, a Norwood-type arch reconstruction (NTAR), is also used in patients with 2 ventricles and a diffusely hypoplastic arch; however, outcomes after NTAR in these patients are not well described. METHODS: A retrospective review was performed of neonates with SV and 2-ventricle (2V) anatomy who underwent an NP or NTAR at our institution from 2000 to 2010. The incidence of recurrent coarctation requiring intervention and associated risk factors were evaluated. RESULTS: Overall, 101 patients with 2V anatomy and 361 patients with SV anatomy were included. Eighteen patients with 2V anatomy (17.8%) and 35 patients with SV anatomy (9.7%) required intervention for recurrent coarctation at a median of 0.5 years (interquartile range [IQR], 0.3-1.2 years) after the initial operation. Independent risk factors associated with recurrent coarctation in patients with 2V anatomy included weight less than 2.5 kg (hazard ratio [HR], 6.05; p = 0.001) and peak aortic arch gradient (PAAG) on the discharge echocardiogram greater than 10 mm Hg (HR, 3.07; p = 0.03). In patients with SV anatomy, shunt type (HR, 6.42; p < 0.0001 for right ventricle to pulmonary artery [RV-PA] shunt compared with others) and peak gradient on the discharge echocardiogram greater than 10 mm Hg were found to be significant (HR, 7.40; p < 0.0001). There was no survival difference in patients with and those without recurrent coarctation. CONCLUSIONS: Recurrent coarctation is common after NTAR. Small patient size and shunt type were found to be independent risk factors for recurrent coarctation in the 2V and SV populations, respectively, and discharge aortic arch gradient was a significant risk factor in both populations. PMID- 27353484 TI - Macrophage-Targeted Indocyanine Green-Neomannosyl Human Serum Albumin for Intraoperative Sentinel Lymph Node Mapping in Porcine Esophagus. AB - BACKGROUND: The sentinel lymph node (SLN) concept has been proposed to avoid unnecessary invasive LN dissection in surgery for esophageal cancer. This study evaluated a new macrophage-targeting fluorescent agent, indocyanine green neomannosyl human serum albumin (ICG:MSA), for SLN mapping using a custom-made intraoperative color and fluorescence-merged imaging system (ICFIS) in porcine esophagus. METHODS: The LN targeting ability of ICG:MSA, indocyanine green-human serum albumin (ICG:HSA), and ICG was examined in vitro using the U937 differentiated monocyte cell line and in vivo in a mouse footpad model using fluorescence imaging. SLN identification in rabbit esophagus was then performed using ICG:MSA, ICG:HSA, and ICG. Finally, intraoperative SLN detection was conducted in porcine esophagus after esophagoscopic injection of ICG:MSA. RESULTS: The fluorescence signal of U937 cells treated by ICG:MSA was significantly higher than that of ICG or ICG:HSA (ICG: 1.0 +/- 0.37; ICG:HSA: 3.4 +/- 0.28, ICG:MSA: 6.8 +/- 1.61; ICG to ICG:HSA, p = 0.03; ICG:HSA to ICG:MSA, p = 0.04; ICG to ICG:MSA, p = 0.0009). ICG:MSA was retained in popliteal LNs as long as 3 h, while ICG rapidly diffused through the entire mouse lymphatic system within 5 min. Esophageal SLN was detected within 15 min after injection of either ICG or ICG:MSA, but ICG:MSA provided more distinguishable images of LNss than ICG in rabbit esophagus. The SLN was also successfully detected in all porcine esophagus; the mean number of SLNs identified per esophagus was 1.6 +/- 0.55. CONCLUSIONS: ICG:MSA has more specific macrophage-targeting properties, which could overcome the limitation of the low SLN retention of ICG, and could provide more precise real-time SLN detection during esophageal cancer surgery. PMID- 27353485 TI - The David V Valve-Sparing Root Replacement Provides Improved Survival Compared With Mechanical Valve-conduits in the Treatment of Young Patients With Aortic Root Pathology. AB - BACKGROUND: Valve-sparing root replacement (VSRR) is an attractive therapy for aortic root aneurysms; however, there is a paucity of data comparing VSRR with conventional root replacement using a mechanical valve-conduit (MECH). This study evaluates and compares outcomes of VSRR and MECH. METHODS: A retrospective review from 2002 to 2015 at a US academic center identified 444 patients who underwent VSRR (282 patients) or MECH (162 patients). Propensity score matching was performed, based on 22 preoperative and intraoperative characteristics, and 87 matched pairs were identified. RESULTS: There was no difference in mean age between the groups (VSRR 45.0 years, MECH 44.2 years, p = 0.59). The incidence of Marfan syndrome (VSRR 10.3%, MECH 12.6%, p = 0.63), type A acute aortic dissection (VSRR 25.3%, MECH 27.6%, p = 0.73), reoperation (VSRR 23.0%, MECH 21.8%, p = 0.86), and arch replacement (VSRR 54.0%, MECH 52.9%, p = 0.88) were similar in both groups. Ejection fraction was similar (VSRR 52.8% +/- 10.9%, MECH 52.4% +/- 11.7%, p = 0.83). Operative mortality was 2.3% with VSRR and 8.0% with MECH (p = 0.10). There were no significant differences in renal failure requiring dialysis (VSRR 1.1%, MECH 4.6%, p = 0.24), permanent neurologic dysfunction (VSRR 2.3%, MECH 6.9%, p = 0.16), and pacemaker implantation (VSRR 1.1%, MECH 1.1%, p = 0.99) between the groups. Survival at 7 years was significantly improved in patients who underwent VSSR (VSRR 85.5%, MECH 73.6%, p = 0.03). CONCLUSIONS: In comparison with patients undergoing MECH, there is improved midterm survival among patients undergoing VSRR, with similar operative mortality and morbidity. For appropriately selected patients, VSRR provides an attractive and potentially superior alternative to MECH. PMID- 27353487 TI - Cross-cultural measurement invariance of the Revised Child Anxiety and Depression Scale across 11 world-wide societies. AB - BACKGROUND: In order to compare estimates by one assessment scale across various cultures/ethnic groups, an important aspect that needs to be demonstrated is that its construct across these groups is invariant when measured using a similar and simultaneous approach (i.e., demonstrated cross-cultural measurement invariance). One of the methods for evaluating measurement invariance is testing for differential item functioning (DIF), which assesses whether different groups respond differently to particular items. The aim of this study was to evaluate the cross-cultural measurement invariance of the Revised Child Anxiety and Depression Scale (RCADS) in societies with different socioeconomic, cultural, and religious backgrounds. METHODS: The study was organised by the International Child Mental Health Study Group. Self-reported data were collected from adolescents residing in 11 countries: Brazil, Bulgaria, Croatia, Indonesia, Montenegro, Nigeria, Palestinian Territories, the Philippines, Portugal, Romania and Serbia. The multiple-indicators multiple-causes model was used to test the RCADS items for DIF across the countries. RESULTS: Ten items exhibited DIF considering all cross-country comparisons. Only one or two items were flagged with DIF in the head-to-head comparisons, while there were three to five items flagged with DIF, when one country was compared with the others. Even with all cross-culturally non-invariant items removed from nine language versions tested, the original factor model representing six anxiety and depressive symptoms subscales was not significantly violated. CONCLUSIONS: There is clear evidence that relatively small number of the RCADS items is non-invariant, especially when comparing two different cultural/ethnic groups, which indicates on its sound cross-cultural validity and suitability for cross-cultural comparisons in adolescent anxiety and depressive symptoms. PMID- 27353488 TI - Understanding the new HHS nondiscrimination rule and how it applies to your facility. PMID- 27353489 TI - Putative function of hypothetical proteins expressed by Clostridium perfringens type A strains and their protective efficacy in mouse model. AB - The whole genome sequencing and annotation of Clostridium perfringens strains revealed several genes coding for proteins of unknown function with no significant similarities to genes in other organisms. Our previous studies clearly demonstrated that hypothetical proteins CPF_2500, CPF_1441, CPF_0876, CPF_0093, CPF_2002, CPF_2314, CPF_1179, CPF_1132, CPF_2853, CPF_0552, CPF_2032, CPF_0438, CPF_1440, CPF_2918, CPF_0656, and CPF_2364 are genuine proteins of C. perfringens expressed in high abundance. This study explored the putative role of these hypothetical proteins using bioinformatic tools and evaluated their potential as putative candidates for prophylaxis. Apart from a group of eight hypothetical proteins (HPs), a putative function was predicted for the rest of the hypothetical proteins using one or more of the algorithms used. The phylogenetic analysis did not suggest an evidence of a horizontal gene transfer event except for HP CPF_0876. HP CPF_2918 is an abundant extracellular protein, unique to C. perfringens species with maximum strain coverage and did not show any significant match in the database. CPF_2918 was cloned, recombinant protein was purified to near homogeneity, and probing with mouse anti-CPF_2918 serum revealed surface localization of the protein in C. perfringens ATCC13124 cultures. The purified recombinant CPF_2918 protein induced antibody production, a mixed Th1 and Th2 kind of response, and provided partial protection to immunized mice in direct C. perfringens challenge. PMID- 27353490 TI - Complete genome analysis of contemporary G12P[8] rotaviruses reveals heterogeneity within Wa-like genomic constellation. AB - G12 rotaviruses are globally emergent rotaviruses causing severe childhood gastroenteritis. Little is known about the evolution and diversity of G12P[8] rotaviruses and the possible role that widespread vaccine use, globally, has had on their emergence. In Sicily, Italy, surveillance activity for rotaviruses has been conducted uninterruptedly since 1985, thus representing a unique observatory for the study of human rotaviruses in the pre- and post-vaccine era. G12 rotaviruses were first detected only in 2012 and between 2012 and 2014 they accounted for 8.7% of all rotavirus-associated infections among children, with peaks of 27.8% in 2012/2013 and 21% in 2014. We determined and analyzed the full genome of 22 G12P[8] rotaviruses collected during the 2012-2014. Although all G12P[8] rotaviruses exhibited a typical Wa-like genotype constellation (G12P[8] I1-R1-C1-M1-A1-N1-T1-E1-H1), phylogenetic analysis allowed distinguishing either two or three (sub)lineages in each genome segment. On the basis of the segregation patterns into lineages/sublineages, 20 G12P[8] rotaviruses could be grouped into three stable major genomic sub-constellations, whilst two strains displayed unique genome architectures, likely due to ressortment with co circulating strains. Altogether, these findings indicate that the onset and prolonged circulation of G12 rotaviruses was due to repeated introductions of different G12 rotaviruses circulating globally. Importantly, as regional rotavirus vaccination was initiated in 2012 reaching a 45% coverage in newborns in 2014, a correlation between the appearance and spread of G12 rotaviruses and the enacted vaccination program could not be drawn. Constant epidemiologic surveillance remains important to monitor the epidemiological dynamics of human rotaviruses. PMID- 27353491 TI - Differential gene expression in mouse spermatogonial stem cells and embryonic stem cells. AB - Mouse spermatogonial stem cells (mSSCs) may be reprogrammed to become pluripotent stem cells under in vitro culture conditions, due to epigenetic modifications, which are closely associated with the expression of transcription factors and epigenetic factors. Thus, this study was conducted to compare the gene expression of transcription factors and epigenetic factors in mSSCs and mouse embryonic stem cells (mESCs). Firstly, the freshly isolated mSSCs [mSSCs (f)] were enriched by magnetic-activated cell sorting with Thy1.2 (CD90.2) microbeads, and the typical morphological characteristics were maintained under in vitro culture conditions for over 5 months to form long-term propagated mSSCs [mSSCs (l)]. These mSSCs (l) expressed pluripotency-associated genes and were induced to differentiate into sperm. Our findings indicated that the mSSCs (l) expressed high levels of the transcription factors, Lin28 and Prmt5, and the epigenetic factors, Tet3, Parp1, Max, Tert and Trf1, in comparison with the mESCs, with the levels of Prmt5, Tet3, Parp1 and Tert significantly higher than those in the mESCs. There was no significant difference in Kdm2b expression between mSSCs (l) and mESCs. Furthermore, the gene expression of N-Myc, Dppa2, Tbx3, Nr5a2, Prmt5, Tet3, Parp1, Max, Tert and Trf1 in the mSSCs (l) was markedly higher in comparison to that in the mSSCs (f). Collectively, our results suggest that the mSSCs and the mESCs displayed differential gene expression profiles, and the mSSCs possessed the potential to acquire pluripotency based on the high expression of transcription factors and epigenetic factors. These data may provide novel insights into the reprogramming mechanism of mSSCs. PMID- 27353492 TI - No effects of oral vitamin D supplementation on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic disorder worldwide, reaching prevalence up to 90 % in obese patients with type 2 diabetes (T2D), and representing an independent risk factor for cardiovascular mortality. Furthermore, the coexistence of T2D and NAFLD leads to higher incidence of diabetes' complications and additive detrimental liver outcomes. The existence of a close association between NAFLD and hypovitaminosis D, along with the anti-inflammatory and insulin-sensitizing properties of vitamin D, have been largely described, but vitamin D effects on hepatic fat content have never been tested in a randomized controlled trial. We assessed the efficacy and safety of 24-week oral high-dose vitamin D supplementation in T2D patients with NAFLD. METHODS: This randomized, double-blind, placebo-controlled trial was carried out at the Diabetes Centre of Sapienza University, Rome, Italy, to assess oral treatment with cholecalciferol (2000 IU/day) or placebo in T2D patients with NAFLD. The primary endpoint was reduction of hepatic fat fraction (HFF) measured by magnetic resonance; as hepatic outcomes, we also investigated changes in serum transaminases, CK18-M30, N-terminal Procollagen III Propeptide (P3NP) levels, and Fatty Liver Index (FLI). Secondary endpoints were improvement in metabolic (fasting glycaemia, HbA1c, lipids, HOMA-IR, HOMA-beta, ADIPO-IR, body fat distribution) and cardiovascular (ankle-brachial index, intima-media thickness, flow-mediated dilatation) parameters from baseline to end of treatment. RESULTS: Sixty-five patients were randomized, 26 (cholecalciferol) and 29 (placebo) subjects completed the study. 25(OH) vitamin D significantly increased in the active treated group (48.15 +/- 23.7 to 89.80 +/- 23.6 nmol/L, P < 0.001); however, no group differences were found in HFF, transaminases, CK18-M30, P3NP levels or FLI after 24 weeks. Vitamin D neither changed the metabolic profile nor the cardiovascular parameters. CONCLUSIONS: Oral high-dose vitamin D supplementation over 24 weeks did not improve hepatic steatosis or metabolic/cardiovascular parameters in T2D patients with NAFLD. Studies with a longer intervention period are warranted for exploring the effect of long time exposure to vitamin D. TRIAL REGISTRATION: This trial was approved on July 2011 by the Ethics Committee of Policlinico Umberto I, Sapienza University of Rome, Italy, and registered at www.clinicaltrialsregister.eu number 2011-003010-17. PMID- 27353493 TI - Usefulness of Microvascular Ultrasonography in Differentiating Metastatic Lymphadenopathy from Tuberculous Lymphadenitis. AB - This study was undertaken to evaluate the usefulness of vascular pattern analysis on microvascular ultrasonography in distinguishing metastatic lymphadenopathy from tuberculous lymphadenitis, compared with conventional power Doppler ultrasonography, and to evaluate inter-observer agreement for microvascular ultrasonography. Thirty-four patients with metastatic lymphadenopathy and 27 patients with tuberculous lymphadenitis were included. The level of inter observer agreement was excellent or good for all aspects of vascular pattern analysis on both ultrasonographic examinations. Vascular distribution, internal vascularity and internal vascular features of lymph nodes on microvascular ultrasonography differed significantly different (p <= 0.002) between metastatic lymphadenopathy and tuberculous lymphadenitis. A central vascular pattern with displacement was prevalent in metastasis, and an avascular pattern was more frequent in tuberculosis. Internal vascularity of metastasis was higher than that of tuberculosis. Vascular patterns on power Doppler ultrasonography did not differ significantly. Vascular pattern analysis using microvascular ultrasonography can be helpful in differentiating metastatic lymphadenopathy from tuberculous lymphadenitis with good inter-observer agreement. PMID- 27353494 TI - Heterologous expression of Cenchritis muricatus protease inhibitor II (CmPI-II) in Pichia pastoris system: Purification, isotopic labeling and preliminary characterization. AB - Cenchritis muricatus protease inhibitor II (CmPI-II) is a tight-binding serine protease inhibitor of the Kazal family with an atypical broad specificity, being active against several proteases such as bovine pancreatic trypsin, human neutrophil elastase and subtilisin A. CmPI-II 3D structures are necessary for understanding the molecular basis of its activity. In the present work, we describe an efficient and straightforward recombinant expression strategy, as well as a cost-effective procedure for isotope labeling for NMR structure determination purposes. The vector pCM101 containing the CmPI-II gene, under the control of Pichia pastoris AOX1 promoter was constructed. Methylotrophic Pichia pastoris strain KM71H was then transformed with the plasmid and the recombinant protein (rCmPI-II) was expressed in benchtop fermenter in unlabeled or (15)N labeled forms using ammonium chloride ((15)N, 99%) as the sole nitrogen source. Protein purification was accomplished by sequential cation exchange chromatography in STREAMLINE DirectHST, anion exchange chromatography on Hitrap Q Sepharose FF and gel filtration on Superdex 75 10/30, yielding high quantities of pure rCmPI-II and (15)N rCmPI-II. Recombinant proteins displayed similar functional features as compared to the natural inhibitor and NMR spectra indicated folded and homogeneously labeled samples, suitable for further studies of structure and protease-inhibitor interactions. PMID- 27353495 TI - Effective non-denaturing purification method for improving the solubility of recombinant actin-binding proteins produced by bacterial expression. AB - Bacterial expression is commonly used to produce recombinant and truncated mutant eukaryotic proteins. However, heterologous protein expression may render synthesized proteins insoluble. The conventional method used to express a poorly soluble protein, which involves denaturation and refolding, is time-consuming and inefficient. There are several non-denaturing approaches that can increase the solubility of recombinant proteins that include using different bacterial cell strains, altering the time of induction, lowering the incubation temperature, and employing different detergents for purification. In this study, we compared several non-denaturing protocols to express and purify two insoluble 34 kDa actin bundling protein mutants. The solubility of the mutant proteins was not affected by any of the approaches except for treatment with the detergent sarkosyl. These results indicate that sarkosyl can effectively improve the solubility of insoluble proteins during bacterial expression. PMID- 27353496 TI - Modelling lifelong effects of different prophylactic treatment strategies for severe haemophilia A. AB - BACKGROUND: Lifelong prophylactic replacement therapy with clotting factor concentrates is recommended for severe haemophilia. The prophylactic dose determines both clinical outcome and treatment cost. In the absence of clinical studies, computer simulation was used to explore lifelong effects and clotting factor consumption for various prophylactic dose levels, and optimize strategies for switching between prophylactic and on-demand treatment. DESIGN AND METHODS: Individual patients' lifetime joint bleeds, radiological arthropathy (Pettersson score, 0-78) and consumption were simulated for each treatment strategy. Treatment effectiveness (expressed as % of patients maintaining a lifetime Pettersson score <=14) and clotting factor consumption were modelled for lifelong prophylaxis at dose levels 1000-4500 IU kg(-1) year(-1) , for on-demand treatment and for switching strategies. Treatment efficiency (consumption per unit of effectiveness) was used to compare strategies. RESULTS: Compared to lifelong on demand treatment, lifelong prophylaxis at 1000 IU kg(-1) year(-1) increased effectiveness from 21 to 36%, at an additional consumption of 0.9 * 10(6) IU kg( 1) . For lifelong prophylaxis, each additional 1000 IU kg(-1) year(-1) resulted in a proportional increase in consumption by +/-5 * 10(6) IU kg(-1) but a less than proportional reduction in arthropathy by +/-50%; consequently, increasing consumption progressively diminished treatment efficiency. Switching strategies slightly reduce effectiveness and consumption. Optimum switching criteria were similar across prophylactic dose levels. CONCLUSION: According to the simulation model, low-dose prophylaxis (1000 IU kg(-1) year(-1) ) improved outcome at a limited increase in consumption compared to on-demand treatment. Increasing prophylactic dose further improved health outcomes, but at decreasing efficiency. Optimal prophylactic dose should therefore be selected balancing acceptable health impact and available budget. PMID- 27353497 TI - Statins, news, and nuance. PMID- 27353498 TI - Unified Synthesis of 10-Oxygenated Lycopodium Alkaloids: Impact of C10 Stereochemistry on Reactivity. AB - The pronounced impact of the C10 stereochemistry on the successful construction of a polycyclic Lycopodium alkaloid scaffold has been explored. A wide range of reaction conditions and functionality were investigated to control a keto sulfone Michael addition to construct the C7-C12 linkage. An unexpected, overriding impact of the C10 stereochemistry in stereoselectivity and reaction rate in the Michael addition was observed. Furthermore, divergent reactivity of a conformationally accelerated, intramolecular Mannich cyclization based on the C10 stereochemistry was discovered. The successful execution of this synthetic route resulted in the total synthesis of all three known 10-oxygenated Lycopodium alkaloids: 10-hydroxylycopodine, paniculine, and deacetylpaniculine. PMID- 27353501 TI - GATS Collaborative Group List. PMID- 27353499 TI - Surrogate endpoints and competing risk of death in cardiac arrest research. AB - We urgently need new therapies to improve outcomes after cardiac arrest. Initial studies typically target surrogate endpoints, and these studies help to inform subsequent larger trials that are powered to measure more patient-orientated clinical outcomes such as survival. The competing risk of death and premature assessment of neurological prognosis pose significant challenges to measuring these surrogate endpoints after cardiac arrest. PMID- 27353502 TI - Dynamic functional characterization and phylogenetic changes due to Long Chain Fatty Acids pulses in biogas reactors. AB - The process stability of biogas plants is often deteriorated by the accumulation of Long Chain Fatty Acids (LCFA). The microbial community shifts due to LCFA disturbances have been poorly understood as the molecular techniques used were not able to identify the genome characteristics of uncultured microorganisms, and additionally, the presence of limited number of reference genomes in public databases prevented the comprehension of specific functional roles characterizing these microorganisms. The present study is the first research which deciphers by means of high throughput shotgun sequencing the dynamics of the microbial community during an inhibitory shock load induced by single pulses of unsaturated LCFA at two different concentrations (i.e. 2 g/L-reactor and 3 g/L-reactor). The metagenomic analysis showed that only the microbes associated with LCFA degradation could encode proteins related to "chemotaxis" and "flagellar assembly", which promoted the ability to move towards the LCFA sources so as to degrade them. Moreover, the syntrophic interactions found between Syntrophomonas sp. together with Methanosarcina sp. were possibly assigned to the menaquinone electron transfer. Finally, it was proven that a previously exposed to LCFA inoculum is more efficient in the degradation process of LCFA due to the specialization of the microbial consortium. PMID- 27353504 TI - Calcium, Strontium and Barium Homogeneous Catalysts for Fine Chemicals Synthesis. AB - The large alkaline earths (Ae), calcium, strontium and barium, have in the past 15 years yielded a brand new generation of heteroleptic molecular catalysts for the production of fine chemicals. However, the integrity of these complexes is often plagued by ligand redistribution equilibria in solution. This personal account retraces the paths followed in our research group towards the design of stable heteroleptic alkalino-earth complexes, including the use of intramolecular noncovalent Ae...H-Si and Ae...F-C interactions. Their implementation as homogenous precatalysts for reactions such as the intramolecular and intermolecular hydroamination and hydrophosphination of activated alkenes, the hydrophosphonylation of ketones, and the dehydrogenative coupling of amines and hydrosilanes that enable the efficient and controlled formations of C?P, C?N, or Si?N sigma-bonds, is presented in a synthetic perspective that highlights their overall outstanding catalytic performance. PMID- 27353503 TI - Multimodal MRI features predict isocitrate dehydrogenase genotype in high-grade gliomas. AB - BACKGROUND: High-grade gliomas with mutations in the isocitrate dehydrogenase (IDH) gene family confer longer overall survival relative to their IDH-wild-type counterparts. Accurate determination of the IDH genotype preoperatively may have both prognostic and diagnostic value. The current study used a machine-learning algorithm to generate a model predictive of IDH genotype in high-grade gliomas based on clinical variables and multimodal features extracted from conventional MRI. METHODS: Preoperative MRIs were obtained for 120 patients with primary grades III (n = 35) and IV (n = 85) glioma in this retrospective study. IDH genotype was confirmed for grade III (32/35, 91%) and IV (22/85, 26%) tumors by immunohistochemistry, spectrometry-based mutation genotyping (OncoMap), or multiplex exome sequencing (OncoPanel). IDH1 and IDH2 mutations were mutually exclusive, and all mutated tumors were collapsed into one IDH-mutated cohort. Cases were randomly assigned to either the training (n = 90) or validation cohort (n = 30). A total of 2970 imaging features were extracted from pre- and postcontrast T1-weighted, T2-weighted, and apparent diffusion coefficient map. Using a random forest algorithm, nonredundant features were integrated with clinical data to generate a model predictive of IDH genotype. RESULTS: Our model achieved accuracies of 86% (area under the curve [AUC] = 0.8830) in the training cohort and 89% (AUC = 0.9231) in the validation cohort. Features with the highest predictive value included patient age as well as parametric intensity, texture, and shape features. CONCLUSION: Using a machine-learning algorithm, we achieved accurate prediction of IDH genotype in high-grade gliomas with preoperative clinical and MRI features. PMID- 27353505 TI - Assessments of fatigue and disease activity in patients with systemic lupus erythematosus enrolled in the Phase 2 clinical trial with blisibimod. AB - This report evaluates the effects of blisibimod (A-623, AMG 623), a potent and selective inhibitor of B-cell activating factor (BAFF), on patient-reported fatigue and disease activity in the Phase 2b PEARL-SC clinical trial in patients with systemic lupus erythematosus (SLE). A total of 547 individuals who met the American College of Rheumatology (ACR) classification criteria for SLE, were positive for anti-double-stranded DNA or antinuclear antibodies, and had a Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score >=6 at baseline, were randomized to receive placebo or blisibimod for at least 24 weeks. Patient self reported fatigue was evaluated using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale, and disease activity was evaluated using Physician's Global Assessment, SELENA-SLEDAI, and British Isles Lupus Assessment Group Score. Statistically significant improvements in FACIT-Fatigue score were observed among individuals randomized to blisibimod, especially in the 200 mg QW group where favorable effects on disease activity with blisibimod compared to placebo were observed as early as Week 8. The mean improvement from baseline of 6.9 points at Week 24, compared with 4.4 points with placebo, met the criteria for minimal clinically important improvement difference defined for patients with SLE. Despite concomitant improvements in FACIT-Fatigue, SLE Responder Index (SRI) and SLE biomarkers (reported previously), FACIT-Fatigue score correlated only weakly with disease activity. While poor correlation between fatigue and disease activity is not new, the observation that correlation remains poor despite concurrent population improvements in disease and fatigue brings a new facet to our understanding of SLE. PMID- 27353507 TI - Security Personnel Practices and Policies in U.S. Hospitals: Findings From a National Survey. AB - Concerns of violence in hospitals warrant examination of current hospital security practices. Cross-sectional survey data were collected from members of a health care security and safety association to examine the type of personnel serving as security in hospitals, their policies and practices related to training and weapon/restraint tool carrying/use, and the broader context in which security personnel work to maintain staff and patient safety, with an emphasis on workplace violence prevention and mitigation. Data pertaining to 340 hospitals suggest security personnel were typically non-sworn officers directly employed (72%) by hospitals. Available tools included handcuffs (96%), batons (56%), oleoresin capsicum products (e.g., pepper spray; 52%), hand guns (52%), conducted electrical weapons (e.g., TASERs(r); 47%), and K9 units (12%). Current workplace violence prevention policy components, as well as recommendations to improve hospital security practices, aligned with Occupational Safety and Health Administration guidelines. Comprehensive efforts to address the safety and effectiveness of hospital security personnel should consider security personnel's relationships with other hospital work groups and hospitals' focus on patients' safety and satisfaction. PMID- 27353506 TI - Can SLE classification rules be effectively applied to diagnose unclear SLE cases? AB - Objective The objective of this paper is to develop novel classification criteria to distinguish between unclear systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) cases. Methods A total of 205 variables from 111 SLE and 55 MCTD patients were evaluated to uncover unique molecular and clinical markers for each disease. Binomial logistic regressions (BLRs) were performed on currently used SLE and MCTD classification criteria sets to obtain six reduced models with power to discriminate between unclear SLE and MCTD patients that were confirmed by receiving operating characteristic (ROC) curve. Decision trees were employed to delineate novel classification rules to discriminate between unclear SLE and MCTD patients. Results SLE and MCTD patients exhibited contrasting molecular markers and clinical manifestations. Furthermore, reduced models highlighted SLE patients exhibiting prevalence of skin rashes and renal disease while MCTD cases show dominance of myositis and muscle weakness. Additionally decision tree analyses revealed a novel classification rule tailored to differentiate unclear SLE and MCTD patients (Lu-vs-M) with an overall accuracy of 88%. Conclusions Validation of our novel proposed classification rule (Lu-vs-M) includes novel contrasting characteristics (calcinosis, CPK elevated and anti-IgM reactivity for U1-70K, U1A and U1C) between SLE and MCTD patients and showed a 33% improvement in distinguishing these disorders when compared to currently used classification criteria sets. Pending additional validation, our novel classification rule is a promising method to distinguish between patients with unclear SLE and MCTD diagnosis. PMID- 27353508 TI - Association Among Sociodemograhic Factors, Work Ability, Health Behavior, and Mental Health Status for Young People After Prolonged Unemployment. AB - The purpose of this study was to explore the associations of prolonged unemployment, health, and work ability among young workers using data from the 2008-2010 Occupational Health Counselling project in Kuopio, Eastern Finland. The total sample for this study was 190 young unemployed adults. The questionnaire included the Work Ability Index (WAI), the Beck Depression Inventory, the Alcohol Use Disorders Identification Test, and the Occupational Health Counselling Survey. Multivariate analyses revealed that men had a higher prevalence of prolonged unemployment than women. Using drugs for purposes other than treatment was associated independently with an increased prevalence of prolonged unemployment. Low WAI scores were associated with a higher prevalence of prolonged unemployment. This study showed that attention should be paid to male workers, those who have poor or moderate work ability and workers who use drugs. Young unemployed workers should be recognized at an early stage. A comprehensive, flexible network of community resources is essential to support young unemployed adults. PMID- 27353509 TI - Musculoskeletal Injury Prevention for New Nurses. AB - Nurses continue to sustain musculoskeletal injuries even with increased emphasis on safe patient handling and mobility (SPHM) and organizational cultures of safety to protect health care workers. Analysis of data from 2011-2014 registered nurse graduates explored hospital safety culture, SPHM education/training, and incidence of new-nurse musculoskeletal injury. Results indicated hospitals provided some type of SPHM education and training, but 46% of study participants were not informed or aware of national SPHM standards or guidelines. Merely 13.9% of participants stated a written "no manual lifting policy" had been implemented; only 32.9% indicated staffing was adequate for SPHM tasks; and only 39.4% stated the hospital had all of the equipment needed to perform SPHM safely. Thirty-nine percent of participants had already sustained a musculoskeletal injury with an additional 35% sustaining but not reporting an injury. More actions are needed to ensure a decrease in musculoskeletal injuries for new nurses. PMID- 27353510 TI - Postpartum blood loss: visual estimation versus objective quantification with a novel birthing drape. AB - INTRODUCTION: Immediate postpartum haemorrhage (PPH) is the most common cause of maternal mortality worldwide. Most recommendations focus on its prevention and management. Visual estimation of blood loss is widely used for the early detection of PPH, but the most appropriate method remains unclear. This study aimed to compare the efficacy of visual estimation and objective measurement using a sterile under-buttock drape, to determine the volume of postpartum blood loss. METHODS: This study evaluated patients aged >= 18 years with low-risk term pregnancies, who delivered vaginally. Immediately after delivery, a birth attendant inserted the drape under the patient's buttocks. Postpartum blood loss was measured by visual estimation and then compared with objective measurement using the drape. All participants received standard intra- and postpartum care. RESULTS: In total, 286 patients with term pregnancies were enrolled. There was a significant difference in postpartum blood loss between visual estimation and objective measurement using the under-buttock drape (178.6 +/- 133.1 mL vs. 259.0 +/- 174.9 mL; p < 0.0001). Regarding accuracy at 100 mL discrete categories of postpartum blood loss, visual estimation was found to be inaccurate, resulting in underestimation, with low correspondence (27.6%) and poor agreement (Cohen's kappa coefficient 0.07; p < 0.05), compared with objective measurement using the drape. Two-thirds of cases of immediate PPH (65.4%) were misdiagnosed using visual estimation. CONCLUSION: Visual estimation is not optimal for measurement of postpartum blood loss in PPH. This method should be withdrawn from standard obstetric practice and replaced with objective measurement using the sterile under-buttock drape. PMID- 27353511 TI - SLC6A3 rs28363170 and rs3836790 variants in Han Chinese patients with sporadic Parkinson's disease. AB - Parkinson's disease (PD; OMIM 168600) is the second most common neurodegenerative disorder characterized by the loss of dopamine-producing neurons in the substantia nigra and other brainstem nuclei. Recently, two variants (rs28363170 and rs3836790) in the solute carrier family 6 member 3 gene (SLC6A3) were identified to be significantly associated with PD patients in French population. The purpose of our study was to explore whether these two variants are associated with sporadic PD in Han Chinese population. We designed a case-control comparison study in 521 Han Chinese patients with sporadic PD and 502 age, gender and ethnicity matched normal controls from Mainland China. There is no statistically significant difference in either genotypic or allelic distribution between disease group and normal controls in our cohort for the two variants (all P>0.05). In addition, we did not identify any related haplotype that would either increase the risk for PD or play a protective role against PD. Our data suggest that variants rs28363170 and rs3836790 are not associated with sporadic PD in Han Chinese population. PMID- 27353512 TI - Association of AKT1 gene polymorphisms with sporadic Parkinson's disease in Chinese Han population. AB - Genetic variants of AKT1 have been shown to influence brain function of Parkinson's disease (PD) patients, and in this paper our aim is to investigate the association between the three single-nucleotide polymorphisms (rs2498799; rs2494732; rs1130214) and PD in Han Chinese. 413 Han Chinese PD patients and 450 healthy age and gender-matched controls were genotyped using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Both the patient and control groups show similar genotype frequencies at the three loci: rs2498799, rs2494732 and rs1130214. We are able to identify a significant difference in the frequencies of genotype (p=0.019) and G allele (OR=0.764, 95% CI=0.587-0.995, p=0.045) both at rs2498799 between the patient and control groups. Furthermore, the association of subjects with GG genotypes versus those with GA+AA genotype remain significant after adjusting for age in the Han Chinese female cohort (OR=0.538, 95%CI=0.345-0.841, p=0.006), which is especially evident in the late-onset cohort (OR=0.521, 95%CI=0.309-0.877, p=0.012). In contrast, allele frequencies at rs2494732 and rs1130214 were similar between patients and controls in all subgroup analyses. These results suggest that polymorphism of AKT1 locus is associated with risk of PD and that the G allele at rs2498799 may decrease the risk of PD in the North-eastern part of Han Chinese female population. PMID- 27353513 TI - Lithium and valproate prevent methylphenidate-induced mania-like behaviors in the hole board test. AB - Manic bipolar is diagnosed by psychomotor agitation, increased goal-directed activity, insomnia, grandiosity, excessive speech, and risky behavior. Animal studies aimed to modeling mania are commonly based in psychostimulants-induced hyperlocomotion. The exploration of other behaviors related with mania is mandatory to investigate this phase of bipolar disorder in animals. In this study, the hole board apparatus was suggested for evaluating mania-like behaviors induced by the psychostimulant methylphenidate. The treatment with methylphenidate (10mg/kg, ip) increased locomotion in the open field test. The pretreatment with lithium (50mg/kg, ip) and valproate (400mg/kg, ip) significantly prevented the hyperlocomotion. In the hole-board test, methylphenidate increased interactions with the central and peripheral holes and the exploration of central areas. Lithium was more effective than valproate in preventing all the behavioral manifestations induced by the psychostimulant. These findings were discussed based on the ability of methylphenidate-treated mice mimicking two symptoms of mania in the hole board test: goal-directed action and risk-taking behavior. In conclusion, the results point to a new approach to study mania through the hole board apparatus. The hole board test appears to be a sensitive assay to detect the efficacy of antimanic drugs. PMID- 27353514 TI - Increased anxiety-like behaviour and altered GABAergic system in the amygdala and cerebellum of VPA rats - An animal model of autism. AB - Anxiety is one of the associated symptoms of autism spectrum disorder. According to the literature, increases in anxiety are accompanied by GABAergic system deregulation. The aim of our study, performed using an animal model of autism in the form of rats prenatally treated with valproic acid (VPA rats), was to investigate changes in anxiety-like behaviour and the gene expression of molecules that control levels of the inhibitory neurotransmitter gamma aminobutyric acid (GABA) in the brain. Anxiety-like behaviours were investigated using zone preferences in the open field test. The levels of the 65 and 67kDa enzymes of l-glutamic acid decarboxylase (GAD) mRNAs and type 1 GABA transporter (GAT1) were evaluated in the amygdala, as well as GABA producing enzymes in the cortex layer of the cerebellum. Our research showed that adult VPA rats spent less time in the inner zone of the testing chamber and more time in the outer zone of the testing chamber in the open field test. We also found that adult VPA rats had increased expression of GAT1 in the amygdala, as well as decreased levels of GAD65 and GAD67 mRNA in the cerebellum compared to control animals. These findings support the existence of a relationship between increased anxiety like behaviour and changes in the regulation of the GABAergic system in VPA rats. PMID- 27353515 TI - Genetic analysis of the CHCHD2 gene in a cohort of Chinese patients with Parkinson disease. AB - CHCHD2 has been recently reported as a causative gene for autosomal dominant Parkinson disease (ADPD) in Japanese populations. Further genetic studies of CHCHD2 in other populations are needed. Herein, we sequenced CHCHD2 gene in 162 patients (90 from ADPD pedigrees, 72 with sporadic Parkinson disease) and 90 healthy controls in Chinese population. We observed 5 exonic variants (c.-34C>A, c.-9T>G, c.5C>T, c.*125G>A, c.*154A>G) including 1 novel variant. No pathogenic mutation was found, suggesting that CHCHD2 mutations may be rare in Chinese ADPD patients. PMID- 27353516 TI - Primary Care Residents Improve Knowledge, Skills, Attitudes, and Practice After a Clinical Curriculum With a Hospice. AB - Effective approaches to teaching attitudes, knowledge, and skills to resident physicians in primary care that can be implemented in any residency program are needed. We examined the feasibility and impact of a single palliative care residency curriculum, including a clinical rotation with a hospice program, across 5 cohorts of residents in 7 divergent primary care residency programs (both family medicine and internal medicine). The didactic content was drawn from the national Education for Physicians on End-of-Life Care Project. A total of 448 residents completed the curriculum. A large effect size was seen in measures of knowledge change (*Cohen d = .89) when compared to a national sample of primary care residency programs. Additionally, measures of confidence to perform palliative care skills and ethical concerns also improved significantly ( P < .001). A frequent comment is wishing the rest of medicine were like that experienced in the hospice setting. In a separate, ancillary evaluation, the average length of stay of patients enrolled in hospice care was 18.5 days longer for the alumni of this program when compared to physicians referring for hospice care who hadn't experienced the curriculum. PMID- 27353517 TI - Next-generation sequencing-based molecular diagnosis of neonatal hypotonia in Chinese Population. AB - Neonatal hypotonia is extremely challenging to diagnose because numerous disorders present similar clinical manifestations. Two panels for diagnosing neonatal hypotonia were developed, which enriches 35 genes corresponding to 61 neonatal hypotonia-related disorders. A cohort of 214 neonates with hypotonia was recruited from 2012 to 2014 in China for this study. Of these subjects, twenty eight neonates with hypotonia were eliminated according to exclusion criteria and 97 were confirmed using traditional detection methods. The clinical diagnoses of the remaining 89 neonates with hypotonia were approached by targeted next generation sequencing (NGS). Among the 89 tested neonates, 25 potentially pathogenic variants in nine genes (RYR1, MECP2, MUT, CDKL5, MPZ, PMM2, MTM1, LAMA2 and DMPK) were identified in 22 patients. Six of these pathogenic variants were novel. Of the 186 neonates with hypotonia, we identified the genetic causes for 117 neonates by the traditional detection methods and targeted NGS, achieving a high solving rate of 62.9%. In addition, we found seven neonates with RETT syndrome carrying five mutations, thus expanding the mutation profiles in Chinese neonates with hypotonia. Our study highlights the utility of comprehensive molecular genetic testing, which provides the advantage of speed and diagnostic specificity without invasive procedures. PMID- 27353518 TI - Introductions do not compensate for functional and phylogenetic losses following extinctions in insular bird assemblages. AB - The ratio of species extinctions to introductions has been comparable for many insular assemblages, suggesting that introductions could have 'compensated' for extinctions. However, the capacity for introduced species to replace ecological roles and evolutionary history lost following extinction is unclear. We investigated changes in bird functional and phylogenetic diversity in the wake of extinctions and introductions across a sample of 32 islands worldwide. We found that extinct and introduced species have comparable functional and phylogenetic alpha diversity. However, this was distributed at different positions in functional space and in the phylogeny, indicating a 'false compensation'. Introduced and extinct species did not have equivalent functional roles nor belong to similar lineages. This makes it unlikely that novel island biotas composed of introduced taxa will be able to maintain ecological roles and represent the evolutionary histories of pre-disturbance assemblages and highlights the importance of evaluating changes in alpha and beta diversity concurrently. PMID- 27353519 TI - The immediate effect of vaginal and caesarean delivery on anal sphincter measurements. AB - OBJECTIVE: This study evaluated the effects of vaginal and caesarean delivery on internal and external anal sphincter muscle thickness using translabial ultrasonography (TL-US). METHODS: This prospective cohort study enrolled nulliparous women who either had vaginal or caesarean deliveries. The thickness of the hypoechoic internal anal sphincter (IAS) and hyperechoic external anal sphincter (EAS) at the 12, 3, 6, and 9 o'clock positions at the distal level were measured before delivery and within 24-48 h after delivery. RESULTS: A total 105 consecutive women were enrolled in the study: 60 in the vaginal delivery group and 45 in the caesarean delivery group. The IAS muscle thickness at the 12 o'clock position in the vaginal delivery group was significantly thicker before compared with after delivery (mean +/- SD: 2.31 +/- 0.74 mm versus 1.81 +/- 0.64 mm, respectively). The EAS muscle thickness at the 12 o'clock position in the vaginal delivery group was significantly thicker before compared with after delivery (mean +/- SD: 2.42 +/- 0.64 mm versus 1.97 +/- 0.85, respectively). CONCLUSIONS: There was significant muscle thinning of both the IAS and EAS at the 12 o'clock position after vaginal delivery, but not after caesarean delivery. PMID- 27353520 TI - Structure of a Novel Phosphotriesterase from Sphingobium sp. TCM1: A Familiar Binuclear Metal Center Embedded in a Seven-Bladed beta-Propeller Protein Fold. AB - A novel phosphotriesterase was recently discovered and purified from Sphingobium sp. TCM1 (Sb-PTE) and shown to catalyze the hydrolysis of a broad spectrum of organophosphate esters with a catalytic efficiency that exceeds 10(6) M(-1) s(-1) for the hydrolysis of triphenyl phosphate. The enzyme was crystallized and the three-dimensional structure determined to a resolution of 2.1 A using single wavelength anomalous diffraction (Protein Data Bank entry 5HRM ). The enzyme adopts a seven-bladed beta-propeller protein fold, and three disulfide bonds were identified between Cys-146 and Cys-242, Cys-411 and Cys-443, and Cys-542 and Cys 559. The active site of Sb-PTE contains a binuclear manganese center that is nearly identical to that of the structurally unrelated phosphotriesterase from Pseudomonas diminuta (Pd-PTE). The two metal ions in the active site are bridged to one another by Glu-201 and a water molecule. The alpha-metal ion is further coordinated to the protein by interactions with His-389, His-475, and Glu-407, whereas the beta-metal ion is further liganded to His-317 and His-258. Computational docking of mimics of the proposed pentavalent reaction intermediates for the hydrolysis of organophosphates was used to provide a model for the binding of chiral substrates in the active site of Sb-PTE. The most striking difference in the catalytic properties of Sb-PTE, relative to those of Pd-PTE, is the enhanced rate of hydrolysis of organophosphate esters with substantially weaker leaving groups. The structural basis for this difference in the catalytic properties between Sb-PTE and Pd-PTE, despite the nearly identical binuclear metal centers for the activation of the substrate and nucleophilic water molecule, is at present unclear. PMID- 27353521 TI - The surgical anatomy of the supraclavicular lymph node flap: A basis for the free vascularized lymph node transfer. AB - BACKGROUND: Vascularized lymph node transfer is an effective surgical method in reducing lymphedema. This study provides the first detailed description of the surgical anatomy of the supraclavicular lymph node flap in regard to pedicle length, pedicle diameter, and the number of lymph nodes and their exact location inside the flap. METHODS: Bilateral supraclavicular dissections of nine fresh cadavers (five female) were performed. Before the dissection, the exact number of lymph nodes was determined sonographically by an experienced radiologist, and their distance from the jugular notch was measured. After anatomic dissection, the vascular pedicle's diameter and length were measured. RESULTS: The mean number of lymph nodes was 1.5 +/- 1.85 on the right side and 3 +/- 2.26 on the left. Their mean distance from the jugular notch was 8.29 +/- 2.15 cm on the right and 6.10 +/- 1.21 cm on the left. The pedicle's length was 4.72 +/- 1.03 cm on the right and 4.86 +/- 0.99 cm on the left, and its diameter 2.03 +/- 0.83 on the right and 1.80 +/- 0.77 on the left. CONCLUSION: The pedicle length and diameter of the supraclavicular lymph node flap are suitable for a microvascular tissue transfer. J. Surg. Oncol. 2017;115:60-62. (c) 2016 Wiley Periodicals, Inc. PMID- 27353522 TI - Two homologous host proteins interact with potato virus X RNAs and CPs and affect viral replication and movement. AB - Because viruses encode only a small number of proteins, all steps of virus infection rely on specific interactions between viruses and hosts. We previously screened several Nicotiana benthamiana (Nb) proteins that interact with the stem loop 1 (SL1) RNA structure located at the 5' end of the potato virus X (PVX) genome. In this study, we characterized two of these proteins (NbCPIP2a and NbCPIP2b), which are homologous and are induced upon PVX infection. Electrophoretic mobility shift assay confirmed that both proteins bind to either SL1(+) or SL1(-) RNAs of PVX. The two proteins also interact with the PVX capsid protein (CP) in planta. Overexpression of NbCPIP2a positively regulated systemic movement of PVX in N. benthamiana, whereas NbCPIP2b overexpression did not affect systemic movement of PVX. Transient overexpression and silencing experiments demonstrated that NbCPIP2a and NbCPIP2b are positive regulators of PVX replication and that the effect on replication was greater for NbCPIP2a than for NbCPIP2b. Although these two host proteins are associated with plasma membranes, PVX infection did not affect their subcellular localization. Taken together, these results indicate that NbCPIP2a and NbCPIP2b specifically bind to PVX SL1 RNAs as well as to CP and enhance PVX replication and movement. PMID- 27353523 TI - Carcinogenic compounds in alcoholic beverages: an update. AB - The consumption of alcoholic beverages has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) since 1988. More recently, in 2010, ethanol as the major constituent of alcoholic beverages and its metabolite acetaldehyde were also classified as carcinogenic to humans. Alcoholic beverages as multi-component mixtures may additionally contain further known or suspected human carcinogens as constituent or contaminant. This review will discuss the occurrence and toxicology of eighteen carcinogenic compounds (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, glyphosate, lead, 3-MCPD, 4-methylimidazole, N nitrosodimethylamine, pulegone, ochratoxin A, safrole) occurring in alcoholic beverages as identified based on monograph reviews by the IARC. For most of the compounds of alcoholic beverages, quantitative risk assessment provided evidence for only a very low risk (such as margins of exposure above 10,000). The highest risk was found for ethanol, which may reach exposures in ranges known to increase the cancer risk even at moderate drinking (margin of exposure around 1). Other constituents that could pose a risk to the drinker were inorganic lead, arsenic, acetaldehyde, cadmium and ethyl carbamate, for most of which mitigation by good manufacturing practices is possible. Nevertheless, due to the major effect of ethanol, the cancer burden due to alcohol consumption can only be reduced by reducing alcohol consumption in general or by lowering the alcoholic strength of beverages. PMID- 27353524 TI - Fermentable soluble fibres spare amino acids in healthy dogs fed a low-protein diet. AB - BACKGROUND: Research in cats has shown that increased fermentation-derived propionic acid and its metabolites can be used as alternative substrates for gluconeogenesis, thus sparing amino acids for other purposes. This amino acid sparing effect could be of particular interest in patients with kidney or liver disease, where this could reduce the kidneys'/liver's burden of N-waste removal. Since dogs are known to have a different metabolism than the obligatory carnivorous cat, the main objective of this study was to assess the possibility of altering amino acid metabolism through intestinal fermentation in healthy dogs. This was studied by supplementing a low-protein diet with fermentable fibres, hereby providing an initial model for future studies in dogs suffering from renal/liver disease. RESULTS: Eight healthy dogs were randomly assigned to one of two treatment groups: sugar beet pulp and guar gum mix (SF: soluble fibre, estimated to mainly stimulate propionic acid production) or cellulose (IF: insoluble fibre). Treatments were incorporated into a low-protein (17 %) extruded dry diet in amounts to obtain similar total dietary fibre (TDF) contents for both diets (9.4 % and 8.2 % for the SF and IF diet, respectively) and were tested in a 4-week crossover feeding trial. Apparent faecal nitrogen digestibility and post prandial fermentation metabolites in faeces and plasma were evaluated. Dogs fed the SF diet showed significantly higher faecal excretion of acetic and propionic acid, resulting in a higher total SCFA excretion compared to IF. SF affected the three to six-hour postprandial plasma acylcarnitine profile by significantly increasing AUC of acetyl-, propionyl-, butyryl- + isobutyryl-, 3-OH-butyryl-, 3 OH-isovaleryl- and malonyl-L-carnitine. Moreover, the amino acid plasma profile at that time was modified as leucine + isoleucine concentrations were significantly increased by SF, and a similar trend for phenylalanine and tyrosine's AUC was found. CONCLUSION: These results indicate that guar gum and sugar beet pulp supplementation diminishes postprandial use of amino acids favoring instead the use of short-chain fatty acids as substrate for the tricarboxylic acid (TCA) cycle. Further research is warranted to investigate the amino acid sparing effect of fermentable fibres in dogs with kidney/liver disease. PMID- 27353525 TI - Central nervous system aspergillosis resembling haemorrhagic brain infarct in a paediatric leukaemia patient. PMID- 27353526 TI - The Hallmarks of Cancer from a Redox Perspective. AB - SIGNIFICANCE: For a healthy cell to turn into a cancer cell and grow out to become a tumor, it needs to undergo a series of complex changes and acquire certain traits, summarized as "The Hallmarks of Cancer." These hallmarks can all be regarded as the result of altered signal transduction cascades and an understanding of these cascades is essential for cancer treatment. RECENT ADVANCES: Redox signaling is a long overlooked form of signal transduction that proceeds through the reversible oxidation of cysteines in proteins and that uses hydrogen peroxide as a second messenger. CRITICAL ISSUES: In this article, we provide examples that show that redox signaling is involved in the regulation of proteins and signaling cascades that play roles in every hallmark of cancer. FUTURE DIRECTIONS: An understanding of how redox signaling and "classical" signal transduction are intertwined could hold promising strategies for cancer therapy in the future. Antioxid. Redox Signal. 25, 300-325. PMID- 27353527 TI - Arsenic-based Life: An active learning assignment for teaching scientific discourse. AB - Among recent high profile scientific debates was the proposal that life could exist with arsenic in place of phosphorous in its nucleic acids and other biomolecules. Soon after its initial publication, scientists across diverse disciplines began to question this extraordinary claim. Using the original article, its claims, its scientific support, and the ensuing counterarguments, a two-day, active learning classroom exercise was developed focusing on the presentation, evaluation, and discussion of scientific argumentation and discourse. In this culminating assignment of a first semester biochemistry course, undergraduate students analyze the scientific support from the original research articles and then present and discuss multiple scientific rebuttals in a lively, civil classroom debate. Through this assignment, students develop a sense of skepticism, especially for the original arsenic-based life claims, and learn to clearly articulate their counterarguments with scientific support and critical reasoning. With its direct integration into first-semester biochemistry curriculum and the excitement surrounding arsenic based life, this assignment provides a robust, simple, and stimulating framework for introducing scientific discourse and active learning into the undergraduate molecular science curriculum. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):40-45, 2017. PMID- 27353528 TI - Interaction between ionic liquid cation and water: infrared predissociation study of [bmim](+).(H2O)n clusters. AB - The infrared predissociation spectra of [bmim](+).(H2O)n, n = 1-8, in the 2800 3800 cm(-1) region are presented and analyzed with the help of electronic structure calculations. The results show that the water molecules solvate [bmim](+) by predominately interacting with the imidazolium C2-H moiety for the small n = 1 and 2 clusters. This is characterized by a redshifted and relatively intense C2-H stretch. For n>= 4 clusters, hydrogen-bond interactions between the water molecules drive the formation of ring isomers which interact on top of the imidazolium ring without any direct interaction with the C2-H. The water arrangement in [bmim](+).(H2O)n is similar to the low energy isomers of neutral water clusters up to the n = 6 cluster. This is not the case for the n = 8 cluster, which has the imidazolium ring disrupting the otherwise preferred cubic water structure. The evolution of the solvation network around [bmim](+) illustrates the competing [bmim](+)-water and water-water interactions. PMID- 27353529 TI - Disturbance-specific social responses in long-finned pilot whales, Globicephala melas. AB - Social interactions among animals can influence their response to disturbance. We investigated responses of long-finned pilot whales to killer whale sound playbacks and two anthropogenic sources of disturbance: tagging effort and naval sonar exposure. The acoustic scene and diving behaviour of tagged individuals were recorded along with the social behaviour of their groups. All three disturbance types resulted in larger group sizes, increasing social cohesion during disturbance. However, the nature and magnitude of other responses differed between disturbance types. Tagging effort resulted in a clear increase in synchrony and a tendency to reduce surface logging and to become silent (21% of cases), whereas pilot whales increased surface resting during sonar exposure. Killer whale sounds elicited increased calling rates and the aggregation of multiple groups, which approached the sound source together. This behaviour appears to represent a mobbing response, a likely adaptive social defence against predators or competitors. All observed response-tactics would reduce risk of loss of group coordination, suggesting that, in social pilot whales, this could drive behavioural responses to disturbance. However, the behavioural means used to achieve social coordination depends upon other considerations, which are disturbance-specific. PMID- 27353530 TI - Lipid transfer proteins and the tuning of compartmental identity in the Golgi apparatus. AB - The Golgi complex constitutes a central way station of the eukaryotic endomembrane system, an intricate network of organelles engaged in control of membrane trafficking and the processing of various cellular components. Previous ideas of compartmental stability within this network are gradually being reshaped by concepts describing a biochemical continuum of hybrid organelles whose constitution is regulated by compartmental maturation. Membrane lipid composition and lipid signaling processes make fundamental contributions to compartmentalization strategies that are themselves critical for organizing cellular architecture and biochemical activities. Phosphatidylinositol transfer proteins (PITPs) are increasingly recognized as key regulators of membrane trafficking through the secretory pathway. They do so by coordinating lipid metabolism with lipid signaling, translating this information to core protein components of the membrane trafficking machinery. In this capacity, PITPs can be viewed as regulators of an essential lipid-protein interface of cisternal maturation. It is also now becoming appreciated, for the first time, that such an interface plays important roles in larger systems processes that link secretory pathway function with cell proliferation. PMID- 27353531 TI - Design, synthesis and biological evaluation of novel 5-fluoro-1H-benzimidazole-4 carboxamide derivatives as potent PARP-1 inhibitors. AB - A series of novel 5-fluorine-benzimidazole-4-carboxamide analogs were designed and synthesized. All target compounds were evaluated for their PARP-1 inhibitory activity. Compounds possessed high intrinsic PARP-1 inhibitory potency have been evaluated in vitro cellular assays to measure the potentiation effect of cytotoxic agents against cancer cell line. These efforts led to the identification of compound 10f, which displayed strong inhibition against the PARP-1 enzyme with an IC50 of 43.7nM, excellent cell inhibitory activity in HCT116 cells (IC50=7.4MUM) and potentiation of temozolomide cytotoxicity in cancer cell line A549 (PF50=1.6). PMID- 27353532 TI - Structural modification of luteolin from Flos Chrysanthemi leads to increased tumor cell growth inhibitory activity. AB - The luteolin from Flos Chrysanthemi was found to directly bind to the Bcl-2 protein and inhibit the tumor cell growth in our previous study. However, it has been shown to possess wide and week biological activities. In this study, a series of derivatives of luteolin were designed and synthesized, and their tumor cell growth inhibitory activities were evaluated against human leukemia cell line HL-60. The results showed that compounds 1B-2, 2A-3, and 2B-5, with hydrophobic substituted benzyl groups introduced to B ring and hydrogen or methyl introduced to 7-OH group of luteolin, exhibited the strongest inhibitory activity with the IC50 lower than 10MUM, which were significantly more potent than luteolin. The studies presented here offer a good example for modifications of flavones to improve their tumor cell growth inhibitory activities. PMID- 27353533 TI - Conversion of adenine to 5-amino-4-pyrimidinylimidazole caused by acetyl capping during solid phase oligonucleotide synthesis. AB - The acetyl capping reaction used throughout solid phase oligonucleotide synthesis is meant to minimize n-1 deletionmer impurities by terminating sequences that fail to couple to a phosphoramidite. However, the reaction is also responsible for the formation of a number of impurities. One capping-related impurity has an additional mass of 98amu from the parent oligonucleotide. The n+98 amu impurity was found to result from modification of an adenine nucleobase. The structure of the impurity was determined by preparation of an oligonucleotide enriched in n+98 amu, enzymatic digestion to individual nucleosides, isolation of the pure nucleoside+98 amu species, crystallization, and X-ray crystallographic analysis. The n+98 amu impurity is an oligonucleotide in which one adenine residue has been converted to 5-amino-4-pyrimidinylimidazole. The mechanism of formation of the impurity was investigated, and a mechanism is proposed. PMID- 27353534 TI - New structure-activity relationships of N-acetamide substituted pyrazolopyrimidines as pharmacological ligands of TSPO. AB - Translocator protein (TSPO) represents an attractive target for molecular imaging and therapy due to its prevalence and critical roles played in oncology and other pathologies. Based upon our previously optimized pyrazolopyrimidine scaffold, we elucidated new structure activity relationships related to N,N-disubstitutions of the terminal acetamide on pyrazolopyrimidines and further explored the impacts of these substituents on lipophilicity and plasma protein binding. Several novel chemical probes reported here exhibited significantly increased binding affinity, suitable lipophilicity and protein binding compared with contemporary TSPO ligands. We illustrate that N,N-acetamide disubstitution affords opportunities to introduce diverse chemical moieties distal to the central pyrazolopyrimidine core, without sacrificing TSPO affinity. We anticipate that further exploration of N-acetamide substitutions may yield additional TSPO ligands capable of furthering the field of precision medicine. PMID- 27353535 TI - Synthesis, characterization and antimicrobial activity of novel Schiff base tethered boronate esters of 1,2-O-isopropylidene-alpha-d-xylofuranose. AB - A series of twenty one Schiff bases based on boronate ester of 1,2-O isopropylidene-alpha-d-xylofuranose scaffold were designed and synthesized by condensation of formyl or amino phenyl boronate esters with substituted anilines or 2-hydroxybenzaldehydes, respectively. All the imines are remarkably stable crystalline solids and were obtained in good yields. All the products were fully characterized by FT-IR, multinuclear NMR ((1)H, (13)C and (11)B) spectroscopy, and elemental analysis. Furthermore, the molecular structures of two of the Schiff bases were established by single crystal X-ray diffraction analysis. All the compounds have been screened for in vitro antimicrobial activity against various Gram-positive and Gram-negative bacterial and fungal strains. They exhibited moderate to good inhibitory activity against most of the tested organisms in comparison with standard drugs. PMID- 27353536 TI - Synthesis and evaluation of 2-pyridinylpyrimidines as inhibitors of HIV-1 structural protein assembly. AB - In an effort to identify an HIV-1 capsid assembly inhibitor with improved solubility and potency, we synthesized two series of pyrimidine analogues based on our earlier lead compound N-(4-(ethoxycarbonyl)phenyl)-2-(pyridine-4 yl)quinazoline-4-amine. In vitro binding experiments showed that our series of 2 pyridine-4-ylpyrimidines had IC50 values higher than 28MUM. Our series of 2 pyridine-3-ylpyrimidines exhibited IC50 values ranging from 3 to 60MUM. The congeners with a fluoro substituent introduced at the 4-N-phenyl moiety, along with a methyl at C-6, represent potent HIV capsid assembly inhibitors binding to the C-terminal domain of the capsid protein. PMID- 27353537 TI - Biomarker Tests for Molecularly Targeted Therapies--The Key to Unlocking Precision Medicine. PMID- 27353538 TI - A Rare Case of Ascites due to Peritoneal Amyloidosis. AB - BACKGROUND: The clinical manifestations of amyloidosis depend on the type of insoluble protein as well as the location of amyloid deposits in tissues or organs. In the gastrointestinal tract, the small intestine is the most common site of amyloid deposits, whereas peritoneal involvement and ascites are rare. CASE REPORT: We report on a case of ascites due to peritoneal amyloidosis. A 65 year-old patient was admitted to our institution due to anasarca and pulmonary congestion, mimicking heart failure. We started the patient on diuretics and vasodilators. Despite improvement in pulmonary congestion and peripheral edema, his ascites was not reduced. Echocardiogram revealed restrictive cardiomyopathy and a speckle-tracking pattern suggestive of cardiac amyloidosis. Subcutaneous and peritoneal biopsies revealed amyloidosis. CONCLUSIONS: Amyloidosis is rare in the peritoneum and is usually asymptomatic. Ascites occurs in only 20% of patients with peritoneal amyloidosis. We searched PubMed using "ascites" and "amyloidosis" and identified only eight case reports of amyloidosis with ascites. Physicians should be particularly careful in heart failure and anasarca cases when ascites is disproportional or not responsive to diuretic treatment. To date, there is no specific treatment for peritoneal amyloidosis. PMID- 27353539 TI - Water-soluble fractions from defatted sesame seeds protect human neuroblast cells against peroxyl radicals and hydrogen peroxide-induced oxidative stress. AB - Oxidative stress is involved in the development of aging-related diseases, such as neurodegenerative diseases. Dietary antioxidants that can protect neuronal cells from oxidative damage play an important role in preventing such diseases. Previously, we reported that water-soluble fractions purified from defatted sesame seed flour exhibit good antioxidant activity in vitro. In the present study, we investigated the protective effects of white and gold sesame seed water soluble fractions (WS-wsf and GS-wsf, respectively) against 2,2'-azobis(2 amidinopropane) dihydrochloride (AAPH) and hydrogen peroxide (H2O2) induced oxidative stress in human neuroblast SH-SY5Y cells. Pretreatment with WS-wsf and GS-wsf did not protect cells against AAPH-induced cytotoxicity, while simultaneous co-treatment with AAPH significantly improved cell viability and inhibited membrane lipid peroxidation. These results suggest that WS-wsf and GS wsf protect cells from AAPH-induced extracellular oxidative damage via direct scavenging of peroxyl radicals. When oxidative stress was induced by H2O2, pretreatment WS-wsf and GS-wsf significantly enhanced cell viability. These results suggest that in addition to radical scavenging, WS-wsf and GS-wsf enhance cellular resistance to intracellular oxidative stress by activation of the Nrf 2/ARE pathway as confirmed by the increased Nrf2 protein level in the nucleus and increased heme oxygenase 1 (HO-1) mRNA expression. The roles of ferulic and vanillic acids as bioactive antioxidants in these fractions were also confirmed. In conclusion, our results indicated that WS-wsf and GS-wsf, which showed antioxidant activity in vitro, are also efficient antioxidants in a cell system protecting SH-SY5Y cells against both extracellular and intracellular oxidative stress. PMID- 27353540 TI - Evaluating the outcomes of the STEPPS programme in a UK community-based population; implications for the multidisciplinary treatment of borderline personality disorder. AB - WHAT IS KNOWN ON THE SUBJECT?: Individuals with a diagnosis of Borderline Personality Disorder (BPD) now constitute a substantial portion of the caseload for community teams. Specialized treatments for BPD often consume a large portion of available psychology resources and also involve lengthy waiting lists. The STEPPS programme is a treatment approach which is growing in evidence, particularly in the US. However, further evidence for the effectiveness of this programme within the UK healthcare system is needed. WHAT THIS STUDY ADDS TO EXISTING KNOWLEDGE: The results of this study support the preliminary evidence for the effectiveness of STEPPS in a UK community-based population. A reduction in symptom severity was in evidence. Novel measures were used to build on previous evaluations of the STEPPS programme. These measures show a significant reduction in patients' affinity for unhelpful schemas, as well as an increase in patients' self-reported quality of life; an important perspective for a recovery focused approach to treatment. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The STEPPS programme has shown its merit as an effective and more accessible treatment option for the community-based treatment of BPD, though some methodological limitations are noted. Furthermore, the results of this study demonstrate that STEPPS can be delivered effectively by teams of facilitators from different professional backgrounds who do not necessarily have extensive training in psychotherapeutic interventions. The result is a well-rounded and diverse skill set possessed by the team of facilitators, adding to the richness of the patient's recovery journey and leading to a more favourable spread of teams' resources. ABSTRACT: Aims & Background Systems Training for Emotional Predictability and Problem Solving (STEPPS) is a group treatment for individuals with a diagnosis of Borderline Personality Disorder (BPD) which has a growing evidence base, particularly in the US. Evidence is sparse for its use with UK populations, and this study seeks to assess the reliability of this evidence, whilst adding to existing knowledge through the use of additional measures. Method Thirty patients completed one of four STEPPS groups. Data regarding symptom severity, quality of life and affinity for maladaptive schemas were collected at the start and end of the group to allow pairwise analysis. Results Significant reductions in symptom severity and affinity for maladaptive schemas were in evidence, as well as highly significant increases in patients' self reported quality of life. Implications The results provide further evidence for the efficacy of STEPPS with a UK sample of patients with a diagnosis of BPD, though limitations with the design of this study warrant caution. They also show that the programme achieves this level of efficacy when delivered by facilitators who are not intensively trained in psychological treatment models. As such, the STEPPS programme provides a resourceful approach to the treatment of BPD in a UK community-based setting. PMID- 27353545 TI - Erratum to "Why do we laugh at misfortunes? An electrophysiological exploration of comic situation processing" [Neuropsychologia 61 (2014) 324-334]. PMID- 27353541 TI - Self-reference in psychosis and depression: a language marker of illness. AB - BACKGROUND: Language use is of increasing interest in the study of mental illness. Analytical approaches range from phenomenological and qualitative to formal computational quantitative methods. Practically, the approach may have utility in predicting clinical outcomes. We harnessed a real-world sample (blog entries) from groups with psychosis, strong beliefs, odd beliefs, illness, mental illness and/or social isolation to validate and extend laboratory findings about lexical differences between psychosis and control subjects. METHOD: We describe the results of two experiments using Linguistic Inquiry and Word Count software to assess word category frequencies. In experiment 1, we compared word use in psychosis and control subjects in the laboratory (23 per group), and related results to subject symptoms. In experiment 2, we examined lexical patterns in blog entries written by people with psychosis and eight comparison groups. In addition to between-group comparisons, we used factor analysis followed by clustering to discern the contributions of strong belief, odd belief and illness identity to lexical patterns. RESULTS: Consistent with others' work, we found that first-person pronouns, biological process words and negative emotion words were more frequent in psychosis language. We tested lexical differences between bloggers with psychosis and multiple relevant comparison groups. Clustering analysis revealed that word use frequencies did not group individuals with strong or odd beliefs, but instead grouped individuals with any illness (mental or physical). CONCLUSIONS: Pairing of laboratory and real-world samples reveals that lexical markers previously identified as specific language changes in depression and psychosis are probably markers of illness in general. PMID- 27353546 TI - Correction: Hydrophobic matrix-free graphene-oxide composites with isotropic and nematic states. AB - Correction for 'Hydrophobic matrix-free graphene-oxide composites with isotropic and nematic states' by Martin Wahlander, et al., Nanoscale, 2016, DOI: 10.1039/c6nr01502f. PMID- 27353547 TI - Synthesis and biological evaluation of 2-fluoro and 3-trifluoromethyl-phenyl piperazinylalkyl derivatives of 1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione as potential antidepressant agents. AB - A series of 2-fluoro and 3-trifluoromethylphenylpiperazinylalkyl derivatives of 1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione (4-21) were synthesized and evaluated for their serotonin (5-HT1A/5-HT7) receptor affinity and phosphodiesterase (PDE4B and PDE10A) inhibitor activity. The study enabled the identification of potent 5 HT1A, 5-HT7 and mixed 5-HT1A/5-HT7 receptor ligands with weak inhibitory potencies for PDE4B and PDE10A. The tests have been completed with the determination of lipophilicity and metabolic stability using micellar electrokinetic chromatography (MEKC) system and human liver microsomes (HLM) model. In preliminary pharmacological in vivo studies, selected compound 8-(5-(4 (2-fluorophenyl)piperazin-1-yl)pentyl)-1,3,7-trimethyl-1H-imidazo[2,1-f]purine 2,4(3H,8H)-dione (9) behaved as a potential antidepressant in forced swim test (FST) in mice. Moreover, potency of antianxiety effects evoked by 9 (2.5 mg/kg) is greater than that of the reference anxiolytic drug, diazepam. Molecular modeling revealed that fluorinated arylpiperazinylalkyl derivatives of 1H imidazo[2,1-f]purine-2,4(3H,8H)-dione have major significance for the provision of lead compounds for antidepressant and/or anxiolytic application. PMID- 27353548 TI - The Value of Deferred Stenting in Acute Myocardial Infarction: Can Minimalist Immediate Mechanical Intervention Do It All? PMID- 27353549 TI - Obesity and diabetes: An update. AB - The twin epidemic of obesity and diabetes is a major crisis globally. Several epidemiologic studies reveal the parallel escalation of obesity and diabetes. The term 'diabesity' expresses their close relationship to each other, wherein both these metabolic disorders are characterized by defects of insulin action. The pathophysiology connecting obesity and diabetes is chiefly attributed to two factors: insulin resistance and insulin deficiency. Recent years have seen an increasing body of work on the following metabolic defects common to both obesity and diabetes such as, impaired tissue perfusion, sleep disturbances, androgen dysfunction, altered Vitamin D levels and GI stress. The scope of this review is to present the most widely accepted theories that link the two diseases, provide an update on some proposed unifying metabolic defects and highlight current and future prevention and management strategies. PMID- 27353550 TI - Biochemical evidence for relaxed substrate specificity of Nalpha acetyltransferase (Rv3420c/rimI) of Mycobacterium tuberculosis. AB - Nalpha-acetylation is a naturally occurring irreversible modification of N termini of proteins catalyzed by Nalpha-acetyltransferases (NATs). Although present in all three domains of life, it is little understood in bacteria. The functional grouping of NATs into six types NatA - NatF, in eukaryotes is based on subunit requirements and stringent substrate specificities. Bacterial orthologs are phylogenetically divergent from eukaryotic NATs, and only a couple of them are characterized biochemically. Accordingly, not much is known about their substrate specificities. Rv3420c of Mycobacterium tuberculosis is a NAT ortholog coding for RimI(Mtb). Using in vitro peptide-based enzyme assays and mass spectrometry methods, we provide evidence that RimI(Mtb) is a protein Nalpha acetyltransferase of relaxed substrate specificity mimicking substrate specificities of eukaryotic NatA, NatC and most competently that of NatE. Also, hitherto unknown acetylation of residues namely, Asp, Glu, Tyr and Leu by a bacterial NAT (RimI(Mtb)) is elucidated, in vitro. Based on in vivo acetylation status, in vitro assay results and genetic context, a plausible cellular substrate for RimI(Mtb) is proposed. PMID- 27353551 TI - Age-Based Tailoring of Adult Spinal Deformity Alignment Goals. PMID- 27353552 TI - Brain Metastasis From Malignant Peripheral Nerve Sheath Tumors. AB - BACKGROUND: Metastatic disease is a well-known sequela of malignant peripheral nerve sheath tumors (MPNSTs). Metastic spread to the brain is unusual. CASE DESCRIPTION: A 56-year-old man was found to have a high grade MPNST of the sciatic nerve. Despite en-bloc excision of the sciatic nerve mass and local radiation postoperatively, he developed pathologically confirmed systemic metastases. He was found to have lung nodules and received chemotherapy 25 months after the diagnosis, and 32 months after the initial diagnosis, he presented with left leg weakness and sensory changes and was found to have a lesion of the frontal lobe for which he received palliative radiation. He developed systemic metastases and died 35 months after initial presentation. We retrospectively reviewed the charts of 179 patients treated at our institution with MPNSTs since 1994. This was the only case of a pathology proven brain metastasis, resulting in an incidence of 0.5%. Literature review revealed 21 cases. The mean age was found to be 37.5 years, and mean survival after development of a brain metastasis was 9.9 months. CONCLUSIONS: Brain metastases from MPNSTs are very rare and represent a poor prognosis, with survival after brain metastasis reported to be approximately 10 months. Early and effective initial diagnosis and treatment of MPNSTs likely represent the best opportunity for increased overall survival. PMID- 27353553 TI - Endovascular Neurosurgery: Personal Experience and Future Perspectives. AB - BACKGROUND: From Luessenhop's early clinical experience until the present day, experimental methods have been introduced to make progress in endovascular neurosurgery. METHODS: A personal historical narrative, spanning the 1980s to 2010s, with a review of past opportunities, current problems, and future perspectives. RESULTS: Although the technology has significantly improved, our clinical culture remains a barrier to methodologically sound and safe innovative care and progress. CONCLUSIONS: We must learn how to safely practice endovascular neurosurgery in the presence of uncertainty and verify patient outcomes in real time. PMID- 27353555 TI - Bioresorbable Intracranial Sensors: A New Frontier for Neurosurgeons. PMID- 27353554 TI - Association Between Comorbidities, Nutritional Status, and Anticlotting Drugs and Neurologic Outcomes in Geriatric Patients with Traumatic Brain Injury. AB - BACKGROUND: Several studies using trauma data banks and registers showed that age, Glasgow Coma Scale (GCS), Injury Severity Score, and intraventricular hemorrhage were independent factors for neurologic outcomes in geriatric patients with traumatic brain injury (TBI). However, these analyses did not comprehensively evaluate factors particularly associated with geriatric patients. We aimed to identify factors particularly associated with geriatric patients that affect neurologic outcomes in TBI. METHODS: Patients aged >=65 years who were hospitalized consecutively in Kagawa University Hospital with severe TBI between 1 January 2008 and 31 October 2015 were retrospectively reviewed. We evaluated background factors particularly associated with geriatric patients, including comorbidities (Charlson Comorbidity Index [CCI]), nutritional status (serum albumin level), and presence/absence of antiplatelet and anticoagulant drugs, in addition to baseline characteristics. Multivariate analyses were performed to identify independent predictors of unfavorable neurologic outcomes (UO), as defined as a Glasgow Outcome Scale score of 1-3 at discharge from hospital. The association between CCI and UO was evaluated in a subgroup analysis. RESULTS: UO occurred in 65.0% of 140 patients. Multivariate analyses showed that the CCI (odds ratio, 1.91; 95% confidence interval, 1.21-3.29; P = 0.011), age, and GCS were independent predictors of UO. In subgroup analyses of patients with an initial GCS score of 13-15, the rate of UO significantly increased with CCI score (CCI 0, 35.5%; CCI 1 or 2, 39.4%; CCI >2, 83.3%; P < 0.01). CONCLUSIONS: CCI was an independent predictor of UO in geriatric patients with severe TBI. PMID- 27353556 TI - Outcome After Decompressive Craniectomy in Different Pathologies. AB - BACKGROUND: We compare the outcome after decompressive craniectomy for various neurologic diseases with the final common pathway of coma, compression of the basal cisterns, a midline shift, or refractory intracranial hypertension. METHODS: Between January 2005 and June 2009, 134 patients underwent decompressive craniectomy for traumatic brain injury (n = 74), intracerebral hemorrhage (n = 21), spontaneous subarachnoid hemorrhage (n = 11), malignant cerebral infarction (n = 27), or encephalitis (n = 1). The outcome was classified at discharge and up to 12 months after treatment in accordance with the Glasgow Outcome Scale (GOS), as well as the Glasgow Coma Scale, Marshall classification, or National Institutes of Health Stroke Scale. Significance was established as P <= 0.05. RESULTS: Median and mean scores on the Glasgow Coma Scale at time of neurosurgical assessment in all patients were <=7. Midline shift was reduced in each subset as a result of surgery (mean, 0.26-0.46 cm; P <= 0.049). Overall outcome based on the median GOS score at discharge ranged from death to severe disability. After 12 months, the median range narrowed to a range of death to persistent vegetative state. At various time points, mean GOS score was not found to differ significantly between the subsets. Unfavorable outcome after 3 months was found in a smaller group of patients after traumatic brain injury than was found in patients with other diseases (P = 0.016). CONCLUSIONS: The outcome after decompressive craniectomy does not differ significantly in different diseases once the final pathophysiologic pathway of refractory intracranial hypertension, coma, compression of the basal cisterns, or midline shift has been reached. PMID- 27353557 TI - Multiple Osseous Loose Bodies Associated with Lumbar Isthmic Spondylolisthesis. AB - BACKGROUND: Multiple osseous loose bodies in the lumbar spine have never been reported. We describe a rare surgical case of multiple osseous loose bodies associated with lumbar isthmic spondylolisthesis. CASE DESCRIPTION: A 74-year-old man who experienced left foot numbness and bilateral gluteal pain was diagnosed with lumbar spondylolisthesis 7 years previously and managed conservatively. He reported recurrence of the left foot numbness 6 months previously, at which time aggressive (rather than conservative) therapy became a consideration. Radiographs of the lumbar spine revealed L5 isthmic spondylolisthesis with dynamic instability at L5/S1. Magnetic resonance imaging of the lumbar spine revealed multiple mass lesions dorsally located in the lumbar canal. Computed tomography myelography demonstrated multiple osseous materials near the isthmic portion at the L5 level where compression of the dural sac by the lesions induced lumbar canal stenosis. The patient underwent posterior decompression surgery that enabled total removal of the osseous lesions. Intraoperative findings revealed osseous lesions located in the fibrocartilage material and no connection of the lytic portion at the L5 level or ligamentum flavum. Postoperative course of the patient was uneventful as his neurological symptoms improved. CONCLUSIONS: We described the first instance of multiple loose bodies in the spinal canal with lumbar canal stenosis. It is presumed that long standing minor trauma due to dynamic instability with a trend of hyperossification induced secondary synovial osteochondromatosis forming multiple loose bodies. PMID- 27353558 TI - Minimal Access Posterior Approach for Extrapleural Thoracic Sympathectomy: A Cadaveric Study and Cases. AB - OBJECTIVE: Operatively, video-assisted thoracoscopic sympathectomy (VATS) involves pleural entry and poses risk in small children and patients with pulmonary disease. A conventional posterior sympathectomy is more invasive than VATS. We investigated a cadaveric feasibility study of a minimal access posterior approach for endoscopic extrapleural sympathectomy and discuss this minimal approach in children with cardiac sympathectomy. METHODS: A posterior endoscopic extrapleural approach for thoracic sympathectomy was performed using lightly embalmed cadavers; surgical corridor depth, width, and associated pleural violation were recorded. Two pediatric cases undergoing secondary prevention for breakthrough cardiac dysrhythmias using this approach are discussed: case 1, a 9 year-old girl with refractory long QT syndrome; and case 2, a 13-year-old boy with hypertrophic cardiomyopathy. RESULTS: The cadaveric study supported 100% identification of a craniocaudal-oriented sympathetic chain using an 18-mm tubular retractor, and a 10% pleural violation rate. There were no clinically significant pneumothoracies in either proof of concept cases. CONCLUSIONS: Minimal access posterior extrapleural sympathectomy is feasible to expose the sympathetic chain in the thoracic region with good visualization using either endoscopic or microscopic magnification. Single-position bilateral thoracic sympathectomy can be performed in pediatric patients with life-threatening ventricular arrhythmias. Based on the cadaveric study and the 2 preliminary cases, we believe that a posterior minimal access approach allows safe and effective access to the thoracic sympathetic chain for causes requiring sympathectomy using single positioning, with minimal risk of pneumothorax or Horner syndrome. PMID- 27353559 TI - Intracerebral Hemorrhage, Vagus Nerve Stimulation, and Anti-Inflammatory Response. PMID- 27353560 TI - Delirium after transcatheter aortic valve implantation via the femoral or apical route. AB - We thought that delirium might be less frequent after transcatheter aortic valve implantation via the femoral artery compared with via the cardiac apex. We reviewed 210 patients who underwent transcatheter aortic valve implantation between January 2009 and October 2014. The proportion (95% CI) of patients who suffered delirium in the 3 days after valve implantation were: 10 (3-16%) in 105 patients who had transfemoral implantation; and 35 (25-45%) in 105 patients who had transapical implantation, p = 0.0001. The variables that independently associated with postoperative delirium were age, male sex and the transapical approach. The median (IQR [range]) hospital stay was 7 (5-13 [2-41]) days and 10 (7-15 [2-64]) days, respectively, p = 0.004. Future trials should focus on different peri-operative management strategies to reduce delirium rates after transcatheter aortic valve implantation, particularly in older men having implantations via the cardiac apex. PMID- 27353561 TI - The Role of Osteopontin in the Pathogenesis and Complications of Type 1 Diabetes Mellitus in Children. AB - OBJECTIVE: Type 1 diabetes mellitus (T1DM) is the most common chronic metabolic disorder of childhood and adolescence. Osteopontin plays a significant role in the development and progression of several autoimmune diseases. Moreover, osteopontin promotes adipose tissue inflammation, dysfunction, and insulin resistance. To investigate the levels of serum osteopontin in pediatric patients with T1DM and to explore if these levels have a role in the prediction of diabetes complications. METHODS: This was a case-control study conducted at the Endocrinology unit of the Children's Hospital of Zagazig University in Egypt, from October 2014 to December 2015. Sixty patients with T1DM and 60 healthy subjects were enrolled. A detailed medical history was taken from all patients/parents. A full clinical examination including ophthalmoscopy was performed on all patients. Fasting blood glucose, hemoglobin A1c (HbA1c), urine albumin/creatinine ratio, and serum osteopontin levels were also determined in all subjects. RESULTS: Patients with T1DM had significantly higher serum osteopontin levels compared with controls (mean +/- standard deviation: 13.7+/ 3.4 MUg/L vs. 8.9+/-2.9 MUg/L, p<0.001). Also, serum osteopontin concentrations were higher in patients with microalbuminuria than in patients with normal albumin excretion rate and in the control group. Similarly, those who had retinal disease had higher osteopontin concentrations than those without (16.8+/-2 vs. 12.4+/-3 mg/L; p=0.005). Serum osteopontin levels correlated with a diagnosis of T1DM, and in diabetic patients, correlated with higher systolic and diastolic blood pressure, body mass index values and with lower high density lipoprotein values, diagnosis of retinopathy, and microalbuminuria. No correlation was found between osteopontin levels and HbA1c, insulin dose, co-medications, and diabetes duration in T1DM patients. The association between high osteopontin levels and T1DM was independent from all confounders. CONCLUSION: This study shows that increased osteopontin levels are independently associated with T1DM in pediatric patients and supports the hypothesis that osteopontin may have a role in the prediction of microvascular diabetes complications. PMID- 27353562 TI - The use of psychiatric services by young adults who came to Sweden as teenage refugees: a national cohort study. AB - AIMS: To investigate the patterns of use of different forms of psychiatric care in refugees who settled in Sweden as teenagers. METHOD: Cox proportional hazards models were used to estimate the use of different forms of psychiatric care from 2009 to 2012 in a population of 35 457 refugees, aged from 20 to 36, who had settled in Sweden as teenagers between 1989 and 2004. These findings were compared with 1.26 million peers from the same birth cohorts in the general Swedish population. RESULTS: Unaccompanied and accompanied refugees were more likely to experience compulsory admission to a psychiatric hospital compared with the native Swedish population, with hazard ratios (HRs) of 2.76 (1.86-4.10) and 1.89 (1.53-2.34), respectively, as well as psychiatric inpatient care, with HRs of 1.62 (1.34-1.94) and 1.37 (1.25-1.50). Outpatient care visits by the young refugees were similar to the native Swedish population. The longer the refugees had residency in Sweden, the more they used outpatient psychiatric care. Refugees born in the Horn of Africa and Iran were most likely to undergo compulsory admission, with HRs of 3.98 (2.12-7.46) and 3.07 (1.52-6.19), respectively. They were also the groups who were most likely to receive inpatient care, with HRs of 1.55 (1.17-2.06) and 1.84 (1.37-2.47), respectively. Our results also indicated that the use of psychiatric care services increased with the level of education in the refugee population, while the opposite was true for the native Swedish population. In fact, the risks of compulsory admissions were particularly higher among refugees who had received a secondary education, compared with native Swedish residents, with HRs of 4.72 (3.06-7.29) for unaccompanied refugees and 2.04 (1.51-2.73) for accompanied refugees. CONCLUSIONS: Young refugees received more psychiatric inpatient care than the native Swedish population, with the highest rates seen in refugees who were not accompanied by their parents. The discrepancy between the use of inpatient and outpatient care by young refugees suggests that there are barriers to outpatient care, but we did note that living in Sweden longer increased the use of outpatient services. Further research is needed to clarify the role that education levels among Sweden's refugee populations have on their mental health and health-seeking behaviour. PMID- 27353564 TI - Mechanistic study of the inhibitory activity of Geum urbanum extract against alpha-Synuclein fibrillation. AB - The presence of Lewy bodies and Lewy neurites is a major pathological hallmark of Parkinson's disease and is hypothesized to be linked to disease development, although this is not yet conclusive. Lewy bodies and Lewy neurites primarily consist of fibrillated alpha-Synuclein; yet, there is no treatment available targeting stabilization of alpha-Synuclein in its native state. The aim of the present study was to investigate the inhibitory activity of an ethanolic extract of Geum urbanum against alpha-Synuclein fibrillation and examine the structural changes of alpha-Synuclein in the presence of the extract. The anti-fibrillation and anti-aggregation activities of the plant extract were monitored by thioflavin T fibrillation assays and size exclusion chromatography, while structural changes were followed by circular dichroism, Fourier transform infrared spectroscopy, intrinsic fluorescence, small angle X-ray scattering and electron microscopy. Since the extract is a complex mixture, structure-function relationships could not be determined. Under the experimental conditions investigated, Geum urbanum was found to inhibit alpha-Synuclein fibrillation in a concentration dependent way, and to partly disintegrate preformed alpha-Synuclein fibrils. Based on the structural changes of alpha-Synuclein in the presence of extract, we propose that Geum urbanum delays alpha-Synuclein fibrillation either by reducing the fibrillation ability of one or more of the aggregation prone intermediates or by directing alpha-Synuclein aggregation towards a non-fibrillar state. However, whether these alterations of the fibrillation pathway lead to less pathogenic species is yet to be determined. PMID- 27353563 TI - Droplet barcoding for massively parallel single-molecule deep sequencing. AB - The ability to accurately sequence long DNA molecules is important across biology, but existing sequencers are limited in read length and accuracy. Here, we demonstrate a method to leverage short-read sequencing to obtain long and accurate reads. Using droplet microfluidics, we isolate, amplify, fragment and barcode single DNA molecules in aqueous picolitre droplets, allowing the full length molecules to be sequenced with multi-fold coverage using short-read sequencing. We show that this approach can provide accurate sequences of up to 10 kb, allowing us to identify rare mutations below the detection limit of conventional sequencing and directly link them into haplotypes. This barcoding methodology can be a powerful tool in sequencing heterogeneous populations such as viruses. PMID- 27353566 TI - Dynamic impact of brief electrical nerve stimulation on the neural immune axis polarization of macrophages toward a pro-repair phenotype in demyelinated peripheral nerve. AB - Demyelinating peripheral nerves are infiltrated by cells of the monocyte lineage, including macrophages, which are highly plastic, existing on a continuum from pro inflammatory M1 to pro-repair M2 phenotypic states. Whether one can therapeutically manipulate demyelinated peripheral nerves to promote a pro-repair M2 phenotype remains to be elucidated. We previously identified brief electrical nerve stimulation (ES) as therapeutically beneficial for remyelination, benefits which include accelerated clearance of macrophages, making us theorize that ES alters the local immune response. Thus, the impact of ES on the immune microenvironment in the zone of demyelination was examined. Adult male rat tibial nerves were focally demyelinated via 1% lysophosphatidyl choline (LPC) injection. Five days later, half underwent 1 hour 20 Hz sciatic nerve ES proximal to the LPC injection site. ES had a remarkable and significant impact, shifting the macrophage phenotype from predominantly pro-inflammatory/M1 toward a predominantly pro-repair/M2 one, as evidenced by an increased incidence of expression of M2-associated phenotypic markers in identified macrophages and a decrease in M1-associated marker expression. This was discernible at 3 days post ES (8 days post-LPC) and continued at the 5 day post-ES (10 days post-LPC) time point examined. ES also affected chemokine (C-C motif) ligand 2 (CCL2; aka MCP-1) expression in a manner that correlated with increases and decreases in macrophage numbers observed in the demyelination zone. The data establish that briefly increasing neuronal activity favorably alters the immune microenvironment in demyelinated nerve, rapidly polarizing macrophages toward a pro-repair phenotype, a beneficial therapeutic concept that may extend to other pathologies. GLIA 2016;64:1546-1561. PMID- 27353565 TI - Two different mechanisms mediate chemotaxis to inorganic phosphate in Pseudomonas aeruginosa. AB - Inorganic phosphate (Pi) is a central signaling molecule that modulates virulence in various pathogens. In Pseudomonas aeruginosa, low Pi concentrations induce transcriptional alterations that increase virulence. Also, under low Pi levels, P. aeruginosa exhibits Pi chemotaxis-a process mediated by the two non-paralogous receptors CtpH and CtpL. Here we show that the two receptors operate via different mechanisms. We demonstrate that the ligand binding domain (LBD) of CtpH but not CtpL binds Pi directly. We identify the periplasmic ligand binding protein PstS as the protein that binds in its Pi loaded state to CtpL, resulting in receptor stimulation. PstS forms part of the Pi transporter and has thus a double function in Pi transport and chemotaxis. The affinity of Pi for CtpH was modest whereas that for PstS very high, which may explain why CtpH and CtpL mediate chemotaxis to high and low Pi concentrations, respectively. The pstS/ctpH double mutant was almost devoid of Pi taxis, indicating that PstS is the only CtpL Pi-shuttle. Chemotaxis mechanisms based on indirect ligand recognition were unambiguously identified in enterobacteria. The discovery of a similar mechanism in a different bacterial order, involving a different chemoreceptor type and chemoeffector suggests that such systems are widespread. PMID- 27353568 TI - Amused, flirting or simply baffled? Is recognition of all emotions affected by traumatic brain injury? AB - OBJECTIVE: This study examined whether people with moderate-severe traumatic brain injury (TBI) display a specific or a general impairment in emotion recognition compared with matched controls, whether these deficits might be accounted for by deficits in other cognitive processes, and whether emotion recognition predicts social functioning following TBI. PARTICIPANTS: Thirty-two participants with TBI and 32 matched controls took part in this study. DESIGN: Participants completed the Complex Audio-Visual Emotion Assessment Task (CAVEAT), a novel measure of emotion recognition, alongside measures of neuropsychological functioning. The TBI group also completed selected self-report measures of psychosocial functioning. RESULTS: Traumatic brain injury participants performed more poorly than controls in recognizing all emotions, rather than displaying a selective impairment in recognizing some emotions (e.g., negative vs. positive) compared with others. Although abstract reasoning, working memory, and processing speed were associated with emotion recognition, injury severity and abstract reasoning were the sole predictors of emotion recognition as measured by the CAVEAT. Emotion recognition accuracy in the TBI group was associated with number of friends and self-reported apathy. CONCLUSION: Emotion recognition deficits are a direct consequence of TBI and have a direct effect on the social dysfunction which is a common outcome of TBI, strengthening the need for targeted remediation. PMID- 27353567 TI - Selective association between cortical thickness and reference abilities in normal aging. AB - A previous study of reference abilities and cortical thickness reported that association between reference abilities and cortical thickness summarized over large ROIs suppressed was suppressed after controlling for mean cortical thickness and global cognition. In this manuscript, we showed that preserving detailed spatial patterns of cortical thickness can identify reference-ability specific association besides the association explained by global cognition and mean cortical thickness. We identified associations between cortical thickness and 3 cognitive reference abilities after controlling for mean thickness, global cognition, and linear chronological age: (1) memory, (2) perceptual speed, and (3) vocabulary. Global cognition was correlated with mean overall thickness but also was found to have a regionally specific pattern of associations. Nonlinear associations between cortical thickness and cognition were not observed, neither were nonlinear age effects. Age-by-thickness interactions were also absent. This implies that all thickness-cognition relations and age associations are independent of age and that consequently no age range is inherently special, since brain-behavioral findings are invariant across the whole age range. PMID- 27353570 TI - What motivates adolescents? Neural responses to rewards and their influence on adolescents' risk taking, learning, and cognitive control. AB - Adolescence is characterized by pronounced changes in motivated behavior, during which emphasis on potential rewards may result in an increased tendency to approach things that are novel and bring potential for positive reinforcement. While this may result in risky and health-endangering behavior, it may also lead to positive consequences, such as behavioral flexibility and greater learning. In this review we will discuss both the maladaptive and adaptive properties of heightened reward-sensitivity in adolescents by reviewing recent cognitive neuroscience findings in relation to behavioral outcomes. First, we identify brain regions involved in processing rewards in adults and adolescents. Second, we discuss how functional changes in reward-related brain activity during adolescence are related to two behavioral domains: risk taking and cognitive control. Finally, we conclude that progress lies in new levels of explanation by further integration of neural results with behavioral theories and computational models. In addition, we highlight that longitudinal measures, and a better conceptualization of adolescence and environmental determinants, are of crucial importance for understanding positive and negative developmental trajectories. PMID- 27353571 TI - Multi-doped carbon dots with ratiometric pH sensing properties for monitoring enzyme catalytic reactions. AB - Multi-doped carbon dots (C-dots) were synthesized using a facile one-pot solvothermal method, and the C-dots can be used as a ratiometric pH probe directly without integrating with other dyes, which was demonstrated by monitoring the proton-producing enzyme catalytic reactions. PMID- 27353572 TI - Replication fork progression is paused in two large chromosomal zones flanking the DNA replication origin in Escherichia coli. AB - Although the speed of nascent DNA synthesis at individual replication forks is relatively uniform in bacterial cells, the dynamics of replication fork progression on the chromosome are hampered by a variety of natural impediments. Genome replication dynamics can be directly measured from an exponentially growing cell population by sequencing newly synthesized DNA strands that were specifically pulse-labeled with the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU). However, a short pulse labeling with BrdU is impracticable for bacteria because of poor incorporation of BrdU into the cells, and thus, the genomewide dynamics of bacterial DNA replication remain undetermined. Using a new thymidine requiring Escherichia coli strain, eCOMB, and high-throughput sequencing, we succeeded in determining the genomewide replication profile in bacterial cells. We also found that fork progression is paused in two ~200-kb chromosomal zones that flank the replication origin in the growing cells. This origin-proximal obstruction to fork progression was overcome by an increased thymidine concentration in the culture medium and enhanced by inhibition of transcription. These indicate that DNA replication near the origin is sensitive to the impediments to fork progression, namely a scarcity of the DNA precursor deoxythymidine triphosphate and probable conflicts between replication and transcription machineries. PMID- 27353573 TI - SAFE Medication Management for Patients With Physical Impairments of Stroke, Part Two. AB - PURPOSE: Part one of this series addressed impairments of stroke affecting motor skills. This second article focuses on the sensory impairments of stroke as they affect medication management: vision, hearing, memory and thinking, communication, and emotional disturbances. DESIGN: Each impairment is discussed, and possible interventions are proposed. Every patient is an individual and requires variable care plans. METHOD: Interventions and strategies, such as tools for assessment, practice tips, and assistive devices, aid patients, families, and their caregivers in practicing safe medication management. FINDINGS: Development of a comprehensive care plan will assist the patient to return as close to previous capabilities as possible. Patient outcomes and successes are variable. CONCLUSIONS AND CLINICAL RELEVANCE: The rehabilitation nurse uses observation, skills, and experience to assess stroke patients' needs and develop strategies to assist the patient in managing their medications. Involving patient, family, and caregivers in the teaching of SAFE (Systematic, Accurate, Functional, Effective) medication management increases safety, decreases the number of adverse drug events, and prevents hospitalizations. PMID- 27353574 TI - A Neural Model of Mind Wandering. AB - The role of the default-mode network (DMN) in the emergence of mind wandering and task-unrelated thought has been studied extensively. In parallel work, mind wandering has been associated with neuromodulation via the locus coeruleus (LC) norepinephrine (LC-NE) system. Here we propose a neural model that links the two systems in an integrative framework. The model attempts to explain how dynamic changes in brain systems give rise to the subjective experience of mind wandering. The model implies a neural and conceptual distinction between an off focus state and an active mind-wandering state and provides a potential neural grounding for well-known cognitive theories of mind wandering. Finally, the proposed neural model of mind wandering generates precise, testable predictions at neural and behavioral levels. PMID- 27353575 TI - Can Ordinary People Detect Deception After All? AB - The tipping point framework of lie detection posits that people can, and do, accurately detect deception. This framework pinpoints three circumstances that aid accuracy: (i) using methods of measurement that circumvent controlled, conscious cognition; (ii) when individual differences or situational factors portend potent risks to lie detection failure, such as in high-stakes or threatening settings; and (iii) when factors diminish concern over the relationship or reputation costs of asserting that someone has lied. We thus depict a psychological system that registers lie detection consistently in nonconscious reactions (e.g., brain based, bodily, indirect social evaluations) and that allows information into consciousness to inform overt assessments of lies when the costs of failing to detect deception exceed those of signaling distrust. PMID- 27353577 TI - Mosquito vectors developing in atypical anthropogenic habitats: Global overview of recent observations, mechanisms and impact on disease transmission. AB - The major mosquito vectors of human diseases have co-evolved with humans over a long period of time. However, the rapid growth in human population and the associated expansion in agricultural activity and greater urbanisation have created ecological changes that have had a marked impact on biology of mosquito vectors. Adaptation of the vectors of malaria and important arbovial diseases over a much shorter time scale to the new types of preimaginal habitats recently created by human population growth and activity is highlighted here in the context of its potential for increasing disease transmission rates. Possible measures that can reduce the effects on the transmission of mosquito-borne diseases are also outlined. PMID- 27353576 TI - Nitrogen and phosphorus uptake rates of different species from a coral reef community after a nutrient pulse. AB - Terrestrial runoff after heavy rainfall can increase nutrient concentrations in waters overlying coral reefs that otherwise experience low nutrient levels. Field measurements during a runoff event showed a sharp increase in nitrate (75-fold), phosphate (31-fold) and ammonium concentrations (3-fold) in waters overlying a fringing reef at the island of Curacao (Southern Caribbean). To understand how benthic reef organisms make use of such nutrient pulses, we determined ammonium, nitrate and phosphate uptake rates for one abundant coral species, turf algae, six macroalgal and two benthic cyanobacterial species in a series of laboratory experiments. Nutrient uptake rates differed among benthic functional groups. The filamentous macroalga Cladophora spp., turf algae and the benthic cyanobacterium Lyngbya majuscula had the highest uptake rates per unit biomass, whereas the coral Madracis mirabilis had the lowest. Combining nutrient uptake rates with the standing biomass of each functional group on the reef, we estimated that the ammonium and phosphate delivered during runoff events is mostly taken up by turf algae and the two macroalgae Lobophora variegata and Dictyota pulchella. Our results support the often proposed, but rarely tested, assumption that turf algae and opportunistic macroalgae primarily benefit from episodic inputs of nutrients to coral reefs. PMID- 27353578 TI - Visceral leishmaniasis epidemiologic evolution in timeframes, based on demographic changes and scientific achievements in Brazil. AB - Visceral leishmaniasis (VL) is a disease of chronic evolution which could be uniformly fatal, if left untreated. Human VL was first described in the Americas in 1913 and in 1936 in Brazil. The number of VL cases in Brazil is increasing steadily in the last three decades. Medical literature highlights this change in the disease epidemiology as a recent urbanization phenomenon, with most of the cases occurring in large cities since 1981, different to that observed previously, like a typical rural endemic. The aim of this study was to create a narrative review of the evolution of VL epidemiology since its first description in Brazil. To describe the process of urbanization of VL, timeframes were created historically consistent with the scientific and public health knowledge obtained about the VL and the demographics changes in Brazil, especially considering the extensive migratory movements in the country due to political or economic events. The first phase of VL was the decades of 30-50 when industrialization triggered internal migration process from countryside to the cities; during this period VL was studied for the first time and described as a rural endemic disease with no relevance to public health. Until the second phase, between the 50s and 80s of the 20th century, demography was characterized by expansion of immigration to the large cities and increase in population density in the suburbs with poor living standards. In this period, there was an advancement in the knowledge of the transmission of the disease being described as the first case acquired in the urban environment. The third phase was characterized by the explosion of cases in Brazilian cities and consolidation of urban endemic transmission. The possibility of urban transmission has been known since the 50s; however, the current phenomenon was due to the creation of ideal conditions for the establishment of transmission cycle in Brazilian cities. PMID- 27353579 TI - Pseudomonas aeruginosa KUN2, extracellular toxins-A potential source for the control of dengue vector. AB - BACKGROUND & OBJECTIVES: Dengue fever is one of the serious health disease transmitted by Aedes spp mosquitoes. The incidence of dengue has increased dramatically around the world in recent decades. Vector control is one of the important strategies practiced for the control of dengue fever. The emergence of resistance among vectors against the existing insecticides has raised new challenges. The aim of the present study was to identify the larvicidal activity of extracellular toxins from Pseudomonas spp for the control of dengue vector, Aedes aegypti. METHODS: Bacterial isolates KUN1, KUN2, KUN3, KUN4, and KUBS were isolated from rhizosphere soil of the agricultural fields in Coimbatore, Tamil Nadu. Lyophilized culture supernatant of KUN2 (24, 48, and 72 h culture) and the solvent extracts from the diethyl ether, petroleum ether, chloroform and ethyl acetate were tested against the IV instar larvae of Ae. aegypti. RESULTS: Morphological and biochemical characterization of KUN2 showed its resemblance to Pseudomonas spp. Further, characterization by molecular methods confirmed it as Pseudomonas aeruginosa. Lyophilized culture supernatant of KUN2 showed more toxicity towards the larvae of Ae. aegypti when grown in the modified medium. Secondary metabolite from the petroleum ether extract was found more toxic to the Ae. aegypti larvae even at low concentration (50 MUg/ml). The supernatant of 48 h culture of KUN2 recorded 100% larvicidal activity when compared to other isolates. Further, the rate of mortality was 100% at 24 h when treated with 100 MUg/ml of petroleum ether extract of KUN2. INTERPRETATION & CONCLUSION: Among the isolates used for the control of Ae. aegypti, the isolate KUN2 showed increased larvicidal activity when grown in the modified medium. The maximum larval mortality was observed in the solvent extract of petroleum ether. The mortality of the larvae might be due to the effect of the toxic compound present in the extract which would have entered the larvae through its cuticle damaging its whole system and obstructing further development. Further, studies on the toxic compound responsible for the larvicidal activity need to be carried out for effective dengue control. PMID- 27353580 TI - Seroprevalence of West Nile virus, Crimean-Congo hemorrhagic fever virus, Francisella tularensis and Borrelia burgdorferi in rural population of Manisa, western Turkey. AB - BACKGROUND & OBJECTIVES: Zoonotic diseases are well recognised threat to public health globally. The information of regional prevalence and associated risk factors allow the national programmes to determine and frame better strategies for their control, as they also provide the actual status of zoonosis in the region. The aim of this study was to determine the seroprevalence of West Nile virus (WNV), Crimean-Congo hemorrhagic fever virus (CCHFV), Francisella tularensis and Borrelia burgdorferi among the rural residents of Manisa region, Turkey and to identify the associated risk factors. METHODS: Cross sectional study was conducted in rural parts of Manisa, Aegean region of western Turkey in 2012. Blood samples from 324 randomly selected subjects were screened for the presence of IgG antibodies to WNV, CCHFV, F. tularensis and B. burgdorferi with commercially available kits. The demographic structure of the rural residents and risk factors related to lifestyle such as outdoor agriculture activities, animal husbandry, hunting and history of tick bite were questioned and their relationships with positive results were analyzed statistically. RESULTS: It was observed that 49 subjects (15%) had IgG antibodies to at least one of the zoonotic agents studied. The seroprevalence of F. tularensis was highest with a percentage of 7.1% (n = 23). Distribution of the positive results for WNV, CCHFV and B. burgdorferi were 4.3% (n = 14), 3.7% (n = 12) and 0.9% (n = 3), respectively. Older age and uncompleted secondary education were the statistically significant risk factors for seropositivity to at least one zoonotic agent investigated. Logistic regression analyses confirmed that older age (over 50) increased the risk of WNV and CCHFV seropositivity. INTERPRETATION & CONCLUSION: Seropositivity rates were not found to be higher than the expected rates. Further, studies are needed to evaluate the threat of vector borne zoonoses and associated risk factors in the study area. PMID- 27353581 TI - Biting behaviour of Anopheles funestus populations in Mutare and Mutasa districts, Manicaland province, Zimbabwe: Implications for the malaria control programme. AB - BACKGROUND & OBJECTIVES: Biting behaviour of Anopheles funestus in Mutare and Mutasa districts, Zimbabwe, is little understood. An investigation was conducted to primarily compare indoor and outdoor biting behaviour of the mosquito, as well as blood meal sources and sporozoite rates. METHODS: Monthly adult anopheline sampling was conducted from October 2013 to September 2014 using Centers for Disease Control light-traps, pyrethrum spray catch and artificial pit shelter methods. Mosquitoes sampled by light-traps were divided into two cohorts. In one cohort, traps were left overnight and mosquitoes were collected the following morning, while in the other set, mosquitoes were collected hourly from 1800-0600 hrs . Collected females were identified using morphological characters and categorised according to their abdominal status. Polymerase chain reaction was used to identify An. funestus sibling species and blood meal sources. Infection rate was tested by enzyme-linked immunosorbent assay. RESULTS: Morphological identification showed that indoor and outdoor catches comprised Anopheles funestus (98.3%) and Anopheles gambiae s.l. (1.7%). Of the 2268 mosquitoes collected, 66.2% were caught by light-traps, and 33.8% were caught resting indoors and outdoors. Anopheles funestus and An. gambiae s.l. were trapped more abundantly indoors (68%) than outdoors (32%). Both indoor and outdoor An. funestus densities were higher in wet (4.3) than dry season (1.8). In Burma Valley and Zindi areas, An. funestus demonstrated variable nocturnal indoor and outdoor flight activity rhythms, with two peaks during the night; between 2200 2300 hrs and 0200- 0400 hrs. Human blood index in An. funestus was 0.64, with Plasmodium falciparum infection rate of 1.8%. INTERPRETATION & CONCLUSION: The present work highlighted important information on the host-seeking behaviour, blood meal sources and infection rates in An. funestus. The information would be helpful in improving the vector control strategies. PMID- 27353582 TI - Spatial analysis of wing geometry in dengue vector mosquito, Aedes aegypti (L.) (Diptera: Culicidae), populations in Metropolitan Manila, Philippines. AB - BACKGROUND & OBJECTIVES: Aedes aegypti (L.) is an efficient vector for arboviral diseases such as dengue. The wings of Ae. aegypti has been extensively studied in order to investigate population heterogeneity and structure by utilizing a landmark based geometric morphometrics (GMs) approach. The aim of this study was to examine and assess the wing geometry of Ae. aegypti in Metropolitan Manila. METHODS: In total, 312 Ae. aegypti mosquitoes were collected from 98 sampling points using a mosquito light-trap from May 2014 to January 2015. A complete coverage of the wing was achieved by removing wing scales with chemical and physical treatment, leading to identification of 26 landmarks. Geometric morphometric analyses were employed and the spatial distance pattern was estimated using isolation by distance (IBD) and spatial autocorrelation (SA). RESULTS: The results of the GM analyses revealed population heterogeneity and structuring in Ae. aegypti populations for both sexes using principal component and canonical variate analyses respectively. Moreover, IBD and SA only detected significant spatial structure in male Ae. aegypti populations while female population structures were homogeneous throughout the geographical area. INTERPRETATION & CONCLUSION: The newly modified wing preparation procedure was able to capture a complete coverage of the wings of Ae. aegypti, thus providing a stronger separation power for very close populations in an urban area. It is also noteworthy that the results of IBD and SA supported the findings of GM in the population structuring of male and female Ae. aegypti. The outcome of the study increases our understanding of the vector, which would be useful in developing effective control strategies. PMID- 27353583 TI - Spatial distribution and insecticide susceptibility status of Aedes aegypti and Aedes albopictus in dengue affected urban areas of Rawalpindi, Pakistan. AB - BACKGROUND & OBJECTIVES: Dengue is one of the most common arthropod-borne viral diseases which is transmitted mainly by two vector species, Aedes aegypti (Linnaeus 1762) and Ae. albopictus (Skuse, 1894) worldwide. As there is no effective medicine and vaccine available, vector control remains the most effective measure to prevent its transmission and outbreak. The aim of the study was to confirm the co-occurrence of Aedes aegypti and Ae. albopictus populations in the different localities of Rawalpindi, Pakistan and examine their susceptibility status against different groups of insecticides. METHODS: Ovitraps were randomly placed in the study localities. The number of eggs from all the ovitraps were counted and incubated for hatching in Medical Entomology and Disease Vector Control (MEDVC) insectarium for rearing up to adult stage. The adults were then identified by using the pictorial keys. Spatial distribution and aggregation of both Ae. aegypti and Ae. albopictus populations was determined by using Index of dispersion or variance to mean ratio and k values of the negative binomial distribution. The susceptibility status of both the species against different insecticides was assessed by using the World Health Organization (WHO) standard bioassay tests. RESULTS: The results showed that there was coexistence among Ae. aegypti and Ae. albopictus populations and the aggregation of their eggs was also observed in all the localities studied in Rawalpindi. Larval bioassays of both the populations exhibited incipient resistance against temephos while adult susceptibility testing results showed that both the species were resistant to DDT, malathion, bendiocarb and permethrin. INTERPRETATION & CONCLUSION: The results suggested that all the field populations of Ae. aegypti and Ae. albopictus existed together and showed qualitative changes in their susceptibility status. Resistance against deltamethrin and lambdacyhalothrin was not confirmed and further investigation was recommended to confirm the change in their susceptibility status. This study could help public health authorities to apply simultaneous control activities on both species due to their coexistence and also resistance management strategies should be formulated to slow down the process of development of resistance. PMID- 27353584 TI - Impact of container material on the development of Aedes aegypti larvae at different temperatures. AB - BACKGROUND & OBJECTIVES: Aedes aegypti, the primary vector of dengue generally breeds in intradomestic and peridomestic containers made up of different materials, i.e. plastic, iron, rubber, earthen material etc. The material of container is likely to affect the temperature of water in container with variation in environmental temperature. The present study was aimed to determine the effect of different container materials on larval development of Ae. aegypti at different temperatures. METHODS: Newly hatched I instar larvae (2-4 h old) were used in the study and experiments were conducted using three different containers made up of plastic, iron and earthen material. Three replicates for each type of container at 22, 26, 30, 34, 38, 40, and 42 degrees C were placed in environmental chamber for the development of larvae. RESULTS: At temperatures >22 degrees C, 50% pupation was completed in earthen pot within 4.3+/-0.6 to 6.3+/ 0.6 days followed by plastic containers (5+/-0 to 8+/-0 days) and iron containers (6+/-0 to 9+/-0 days). Developmental time for 50% pupation in the three containers differed significantly (p < 0.05) at all the experimental temperature ranges. A significant variation was found in the temperature of environmental chamber and the temperature of water in three types of containers (p < 0.05). The difference in the temperatures of water in different containers resulted in significant variations in the developmental period of larvae. More than 35 degrees C temperature of water was found inimical for pupal development. INTERPRETATION & CONCLUSION: The results revealed the variation in temperature of water in different types of containers depending on the material of container, affecting duration of larval development. As the larval development was faster in earthen pot as compared to plastic and iron containers, community should be discouraged for storing the water in earthen pots. However, in view of containers of different materials used by the community in different temperature zones in the country, further studies are required for devising area-specific preventive measures for Aedes breeding. PMID- 27353585 TI - Molecular identification of Aedes aegypti mosquitoes from Pilani region of Rajasthan, India. AB - BACKGROUND & OBJECTIVES: Aedes aegypti is the most important vector of dengue virus infection in humans worldwide. Accurate identification and colonization are the essential requirements to understand vector biology as well as its diseases transmission potential. In this study, we have used molecular approaches for the identification of Ae. aegypti mosquitoes that were collected from the Pilani region of Rajasthan, India Methods: Field collected mosquito larvae were colonized under laboratory conditions. Conserved genetic markers, ITS-2 and mtCOI were used for amplification through species-specific primers to identify the mosquito species/ strain. Sequencing result of this strain was phylogenetically compared with other global strains through MEGA software. RESULTS: A comprehensive multiple sequence alignment and phylogenetic analysis revealed that COI gene of Ae. aegypti has extremely low genetic variability with one of the Indian isolate from Thirumala, Andhra Pradesh region (GenBank: HM807262.1). However, in context of different geographical locations, it indicated close similarity with Thailand's strain and high variability when compared with Madagascar strain. On the other hand, ITS-2 illustrated highest identity with Ae. aegypti of Saudi Arabia (GenBank: JX423807.1) whereas, high divergence was observed from Mayotte, France strain (GenBank: KF135506). INTERPRETATION & CONCLUSION: The findings suggest that this isolate from Rajasthan is similar to other Asian continent strains possibly due to the same origin. Understanding the vectorial capacity of these geographically distributed mosquito strains will enhance our knowledge to improve existing vector surveillance and control programme. PMID- 27353586 TI - In silico evaluation of inhibitory potential of triterpenoids from Azadirachta indica against therapeutic target of dengue virus, NS2B-NS3 protease. AB - BACKGROUND & OBJECTIVES: NS2B-NS3 protease (NS2B-NS3 pro ) of dengue virus (DENV) is the prime therapeutic target for the development of anti-dengue drug to combat the DENV infection, which is currently an increasing health problem in many countries. In the area of antiviral drug discovery, numerous reports on the antiviral activity of various medicinal plants against dengue viruses have been published. Neem plant (Azadirachta indica) is one among those medicinal plants which is reported to show potential antiviral activity against DENV. But active principle of neem plant extract which has inhibitory potential against DENV NS2B NS3 pro is not yet reported. The aim of the present study was to explore the inhibitory potential of five triterpenoids from neem plant, viz. nimbin, desacetylnimbin, desacetylsalannin, azadirachtin and salannin, against DENV NS2B NS3 pro. METHODS: The molecular 3D structural data of DENV NS2B-NS3 pro and selected triterpenoids of neem plant were collected from protein databank (PDB ID: 2VBC) and PubChem database respectively. The molecular docking approach was employed to find out the in silico inhibitory potential of the five triterpenoids against DENV NS2B- NS3 pro. RESULTS: The molecular docking results showed that nimbin, desacetylnimbin and desacetylsalannin have good binding affinity with DENV NS2B-NS3 pro , while azadirachtin and salannin did not show any interaction with the target protein. It was observed that the DENV NS2B-NS3 pro binding energy for nimbin, desacetylnimbin and desacetylsalannin were -5.56, -5.24 and 3.43 kcal/mol, respectively. INTERPRETATION & CONCLUSION: The findings attained through this study on the molecular interaction mode of three neem triterpenoids and DENV NS2B-NS3 pro can be considered for further in vitro and in vivo validation for designing new potential drugs for DENV infection. PMID- 27353587 TI - Examination of the specific clinical symptoms and laboratory findings of Crimean Congo hemorrhagic fever. AB - BACKGROUND & OBJECTIVES: Crimean-Congo hemorrhagic fever (CCHF) is a fatal disease, caused by a tick-borne virus (Nairovirus), having a high mortality rate. The study was aimed to evaluate the risk factors, the presenting symptoms and findings of the patients with prediagnosis of CCHF disease, and to compare these variables between the CCHF-positive and CCHF-negative patients. It was also aimed to develop a scoring formula for the diagnosis of CCHF. METHODS: In total, 281 patients who were admitted to the Sabuncuoglu Serafeddin Training and Research Hospital, Amasya, Turkey between 2011 and 2015 and were prediagnosed with CCHF based on the clinical symptoms, laboratory findings and risk factors were included in the study. The definitive laboratory diagnosis of patients with prediagnosis of CCHF was ensured via molecular and serological methods. In addition, a mathematical diagnostic scoring formula was developed for enhancing the laboratory results of CCHF. RESULTS: The ratio of certain clinical symptoms such as fever (p<0.001), headache (p<0.001), widespread body pain (p<0.001), fatigue (p = 0.001), nausea and vomiting (p = 0.013) in CCHF-positive patients were found to be significantly higher compared to the ratio in CCHF-negative patients. In terms of laboratory findings such as presence of leucopenia (p<0.001), creatine kinase (CK) elevation (p<0.001), thrombocytopenia (p<0.001), aspartate aminotransferase/alanine aminotransferase (AST/ALT) elevation (p<0.001), lactate dehydrogenase (LDH) levels (p = 0.002), absence of abnormal findings on chest radiograph (p = 0.042), and the absence of anaemia (p = 0.007), the CCHF-positive patients had higher rates in comparison to CCHF-negative ones. INTERPRETATION & CONCLUSION: It was inferred that certain clinical symptoms and laboratory findings such as fever, headache, widespread body pain, fatigue, leucopenia, nausea, vomiting, high CK levels, thrombocytopenia, AST/ ALT elevation and elevated LDH levels are highly specific and are required to be considered in the definitive diagnosis of CCHF, particularly in regions where this infection is observed as endemic. PMID- 27353589 TI - Molecular docking and simulation studies of gustatory receptor of Aedes aegypti: A potent drug target to distract host-seeking behaviour in mosquitoes. AB - BACKGROUND & OBJECTIVES: It is well reported that exhaled CO 2 and skin odour from human being assist female mosquitoes to locate human host. Basically, the receptors for this activity are expressed in cpA neurons. In both Aedes aegypti and Anopheles gambiae, this CO 2-sensitive olfactory neuron detects myriad number of chemicals present in human skin. Therefore, manipulation of gustatory receptors housing these neurons may serve as important targets for behavioural intervention. The study was aimed towards virtual screening of small molecules in the analyzed conserved active site residues of gustatory receptor and molecular dynamics simulation study of optimum protein-ligand complex to identify a suitable lead molecule for distracting host-seeking behaviour of mosquitoes. METHODS: The conserved residue analysis of gustatory receptor (GR) of Ae. aegypti and An. gambiae was performed. The structure of GR protein from Ae. aegypti was modeled and validated, and then molecular docking was performed to screen 2903 small molecules against the predicted active residues of GR. Further, simulation studies were also carried out to prove protein-ligand stability. RESULTS: The glutamine 154 residue of GR was found to be highly conserved in Ae. aegypti and An. gambiae. Docking results indicated that the dodecanoic acid, 1,2,3 propanetriyl ester (dynasan 112) was interacting with this residue, as it showed better LibDock score than previously reported ethyl acetate used as mosquito repellant. Simulation studies indicated the structural instability of GR protein in docked form with dynasan 112 suggesting its involvement in structural changes. Based on the interaction energies and stability, this compound has been proposed to be used in mosquitoes' repellant. INTERPRETATION & CONCLUSION: A novel effective odorant acting as inhibitor of GR is proposed based on its stability, docking score, interactions and RMSD, considering ethyl pyruvate as a standard inhibitor. Host preference and host-seeking ability of mosquito vectors play key roles in disease transmission, a clear understanding of these aspects is essential for preventing the spread of the disease. PMID- 27353588 TI - Monitoring the efficacy of antimalarial medicines in India via sentinel sites: Outcomes and risk factors for treatment failure. AB - BACKGROUND & OBJECTIVES: To combat the problem of antimalarial drug resistance, monitoring the changes in drug efficacy over time through periodic surveillance is essential. Since 2009, systematic and continuous monitoring is being done through nationwide sentinel site system. Potential early warning signs like partner drug resistance markers were also monitored in the clinical samples from the study areas. METHODS: A total of 1864 patients with acute uncomplicated malaria were enrolled in therapeutic efficacy studies of artesunate plus sulphadoxine-pyrimethamine (AS+SP) for Plasmodium falciparum; those infected with P. vivax were given chloroquine (CQ). Polymerase chain reaction (PCR) was used to distinguish post-treatment reinfection from treatment failures. Isolates of P. falciparum were also analysed for dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) gene mutations. RESULTS: Overall, 1687 (91.7%) patients completed the follow-up. In most of the falciparum patients the parasitaemia was cleared within 24 h of treatment, except 12 patients who remained parasite positive after 72 h. Presence of dhfr and dhps quintuple mutation was observed predominantly in treatment failure samples. A daily dose of artesunate of < 3 mg/kg of body weight, age of <5 yr, and fever at enrolment were associated with an increased risk of treatment failure. The AS+SP in P. falciparum was effective in > 95% cases in all the sentinel sites except in Northeastern region (NE). Chloroquine remained 100% efficacious in case of P. vivax infections. INTERPRETATION & CONCLUSION: Till 2012, India's national antimalarial drug resistance monitoring system proved highly efficacious and safe towards first-line antimalarials used in the country, except in Northeastern region where a decline in efficacy of AS+SP has been observed. This led to change in first-line treatment for P. falciparum to artemether-lumefantrine in Northeastern region. PMID- 27353590 TI - Molecular confirmation of scrub typhus infection and characterization of Orientia tsutsugamushi genotype from Karnataka, India. PMID- 27353591 TI - Expansion of visceral leishmaniasis to northwest sub-Himalayan region of India: A case series. PMID- 27353592 TI - NS1 antigen positivity rate in canine sera from dengue endemic area. PMID- 27353594 TI - Impact of Diradical Spin State (Singlet vs Triplet) and Structure (Puckered vs Planar) on the Photodenitrogenation Stereoselectivity of 2,3 Diazabicyclo[2.2.1]heptanes. AB - Versatile transformations of azo compounds are utilized not only in synthetic organic chemistry but also in materials science. In this study, a hitherto unknown stereoselectivity was observed by low-temperature in situ NMR spectroscopy for the photochemical denitrogenation of a cyclic azoalkane (2,3 diazabicyclo[2.2.1]heptane) derivative. Direct (singlet) photodenitrogenation at 188 K afforded two products, the configurationally retained ring-closed compound (ret-CP) and the inverted compound (inv-CP), in a ratio of 82/18 (+/-3) (ret CP/inv-CP), with an overall yield of >95%. Triplet-sensitized denitrogenation at 199 K using benzophenone ((3)BP*) or xanthone ((3)Xan*) selectively produced inv CP, with a ret-CP/inv-CP ratio of 7/93 (+/-3). Thermal isomerization of inv-CP into ret-CP was observed by low-temperature NMR spectroscopy. Transient absorption spectroscopy revealed that two distinct singlet diradicals are involved in the formation of CP during direct photodenitrogenation, that is, puckered puc-(1)DR and planar pl-(1)DR diradicals. The former produces ret-CP, whereas the latter affords inv-CP. Kinetic analysis using the integrated profiles method was used to determine the molecular absorption coefficient of pl-(1)DR (epsilon560 = 4900 +/- 250 M(-1) cm(-1)) for the first time. The involvement of the puckered singlet diradical resolves the mechanistic puzzle of stereoselective denitrogenation of diazabicycloheptane-type azoalkanes. PMID- 27353593 TI - Implementation of an in-house quantitative real-time polymerase chain reaction method for Hepatitis B virus quantification in West African countries. AB - Hepatitis B virus (HBV) is a major cause of chronic liver disease worldwide. HBV infection is diagnosed by serological tests, while real-time polymerase chain reaction (qRT-PCR) assays are used to quantify viral load, which is a crucial parameter to determine viral replication and to monitor antiviral treatments. However, measuring viral load in resource-limited countries remains nonsystematic, due to the high cost of commercial kits. Here, we describe the development, validation and implementation of a low-cost, in-house qRT-PCR assay to monitor HBV viral load in chronic carriers enrolled in the PROLIFICA programme in the Gambia and Senegal. Over 1500 HBsAg-positive patients, including 210 chronically infected HBV patients, who were given antiviral treatment (tenofovir), were monitored by qRT-PCR using the SYBR Green- and HBV-specific primers. Twenty-four tenofovir-treated patients were followed up and their viral load was tested every 3 months over the 12-month experimental time course. Compared to commercial assays, our in-house assay was shown to be (i) highly reliable, with good intra- and interassay reproducibility over a wide range (45 4.5 * 108 copies mL-1 ), (ii) very similar in the viral loads detected (R2 = .90), (iii) highly sensitive, as it detected loads as low as 30 copies mL-1 (~5 IU mL-1 ), (iv) cheaper (2- to 3-fold), (v) easier to implement and (vi) more rapid. Based on our experience, we recommend this assay as a reliable alternative to commercial assays, for monitoring HBV viraemia in resource-limited, highly endemic countries to reduce the cost and technical obstacles associated with commercial kits. PMID- 27353595 TI - In vitro and in vivo evaluation of 2-aminoalkanol and 1,2-alkanediamine derivatives against Strongyloides venezuelensis. AB - BACKGROUND: Strongyloidiasis is a parasitic disease widely present in tropical and subtropical areas. Strongyloides stercoralis represents the main species that infects human beings. Ivermectin is the current drug of choice; however, issues related with treatment failure in patients with diabetes or infected with T lymphotropic virus-1 make the identification of new molecules for alternative treatment a priority. In the present study, the activity of sphingosine-related aminoalcohol and diamine were evaluated against Strongyloides venezuelensis third stage larva (L3) cultures and experimental infections in mice. METHODS: The efficacy of each compound against L3 was assessed using both XTT (2,3-bis-(2 methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) assay and microscopic observation with concentrations ranging from 1 to 350 MUM. Cytotoxicity was evaluated using J774.2 macrophage cell line and XTT assay. Lethal concentration 50 (LC50), selectivity index (SI) and structure-activity relationships were established. The activity compounds 4 (2-(ethylamino) hexadecan-1-ol), 6 (2-(butylamino) hexadecan-1-ol), 17 (tert-butyl N-(1 aminododecan-2-yl) carbamate) and 18 (tert-butyl N-(1-aminohexadecan-2-yl) carbamate) were further assessed against experimental S. venezuelensis infections in CD1 mice measuring reductions in the numbers of parthenogenetic females and egg passed in faeces. Mice were infected with 3,000 L3 and treated with 20 mg/kg/day for five days. RESULTS: In the screening study of 15 aminoalcohols [lauryl (n = 9); palmityl (n = 13); stearyl (n = 15) and alcohol derivatives], the presence of a palmitol chain was associated with the highest efficacy against L3 (LC50 31.9-39.1 MUM). Alkylation of the 2-amino group with medium size fragments as ethyl or n-butyl showed the best larvicidal activity. The dialkylation did not improve efficacy. Aminoalcohols 4 and 6 showed the highest SI (1.5 and 1.6, respectively). With respect to diamine derivative compounds, a chain size of sixteen carbon atoms (palmitoyl chain, n = 13), and the alkylation of the 2-amino group with medium-sized fragments, were associated with the highest lethal activities. The presence of carbamoyl group in diamines 17 and 18 yielded high SI (1.7 and 1.4, respectively). Infected mice treated with aminoalcohol 6 showed reduction in parthenogenetic females (59 %) and eggs in faeces (51 %). CONCLUSIONS: These results support the potentiality of aminoalcohol and diamine sphingosine-related compounds as suitable prototypes for developing new promising drugs against strongyloidiasis. PMID- 27353596 TI - Risk of hip, subtrochanteric, and femoral shaft fractures among mid and long term users of alendronate: nationwide cohort and nested case-control study. AB - OBJECTIVES: To determine the skeletal safety and efficacy of long term (>=10 years) alendronate use in patients with osteoporosis. DESIGN: Open register based cohort study containing two nested case control studies. SETTING: Nationwide study of population of Denmark. PARTICIPANTS: 61 990 men and women aged 50-94 at the start of treatment, who had not previously taken alendronate, 1996-2007. INTERVENTIONS: Treatment with alendronate. MAIN OUTCOME MEASURES: Incident fracture of the subtrochanteric femur or femoral shaft (ST/FS) or the hip. Non-fracture controls from the cohort were matched to fracture cases by sex, year of birth, and year of initiation of alendronate treatment. Conditional logistic regression models were fitted to calculate odds ratios with and without adjustment for comorbidity and comedications. Sensitivity analyses investigated subsequent treatment with other drugs for osteoporosis. RESULTS: 1428 participants sustained a ST/FS (incidence rate 3.4/1000 person years, 95% confidence interval 3.2 to 3.6), and 6784 sustained a hip fracture (16.2/1000 person years, 15.8 to 16.6). The risk of ST/FS was lower with high adherence to treatment with alendronate (medication possession ratio (MPR, a proxy for compliance) >80%) compared with poor adherence (MPR <50%; odds ratio 0.88, 0.77 to 0.99; P=0.05). Multivariable adjustment attenuated this association (adjusted odds ratio 0.88, 0.77 to 1.01; P=0.08). The risk was no higher in long term users (>=10 dose years; 0.70, 0.44 to 1.11; P=0.13) or in current compared with past users (0.91, 0.79 to 1.06; P=0.22). Similarly, MPR >80% was associated with a decreased risk of hip fracture (0.73, 0.68 to 0.78; P<0.001) as was longer term cumulative use for 5-10 dose years (0.74, 0.67 to 0.83; P<0.001) or >=10 dose years (0.74, 0.56 to 0.97; P=0.03). CONCLUSIONS: These findings support an acceptable balance between benefit and risk with treatment with alendronate in terms of fracture outcomes, even for over 10 years of continuous use. PMID- 27353597 TI - Leptin suppresses sweet taste responses of enteroendocrine STC-1 cells. AB - Leptin is an important hormone that regulates food intake and energy homeostasis by acting on central and peripheral targets. In the gustatory system, leptin is known to selectively suppress sweet responses by inhibiting the activation of sweet sensitive taste cells. Sweet taste receptor (T1R2+T1R3) is also expressed in gut enteroendocrine cells and contributes to nutrient sensing, hormone release and glucose absorption. Because of the similarities in expression patterns between enteroendocrine and taste receptor cells, we hypothesized that they may also share similar mechanisms used to modify/regulate the sweet responsiveness of these cells by leptin. Here, we used mouse enteroendocrine cell line STC-1 and examined potential effect of leptin on Ca(2+) responses of STC-1 cells to various taste compounds. Ca(2+) responses to sweet compounds in STC-1 cells were suppressed by a rodent T1R3 inhibitor gurmarin, suggesting the involvement of T1R3-dependent receptors in detection of sweet compounds. Responses to sweet substances were suppressed by ?1ng/ml leptin without affecting responses to bitter, umami and salty compounds. This effect was inhibited by a leptin antagonist (mutant L39A/D40A/F41A) and by ATP gated K(+) (KATP) channel closer glibenclamide, suggesting that leptin affects sweet taste responses of enteroendocrine cells via activation of leptin receptor and KATP channel expressed in these cells. Moreover, leptin selectively inhibited sweet-induced but not bitter-induced glucagon-like peptide-1 (GLP-1) secretion from STC-1 cells. These results suggest that leptin modulates sweet taste responses of enteroendocrine cells to regulate nutrient sensing, hormone release and glucose absorption in the gut. PMID- 27353598 TI - Guidelines for Evaluation and Management of Cognitive Disorders in HIV-Positive Individuals. AB - Antiretroviral therapy has revolutionised the treatment for people living with HIV (PLWH). Where antiretroviral coverage is high, the treatment paradigm for HIV disease is now one of managing the long-term consequences of the virus and its treatment rather than the consequences of untreated HIV-disease such as immunosuppression and opportunistic infections. One such long-term consequence is HIV-associated cognitive impairment which is reported to occur in up to 50 % of treated PLWH and has been associated with poorer outcomes. Given the ageing cohort and increased frequency of comorbidities, the prevalence of symptomatic cognitive impairment may increase with time. High quality evidence for management strategies including screening, diagnosis and treatment of HIV-associated cognitive impairment are lacking and in general guidelines are based on best clinical practice. In this article, we assessed recent guidelines concerning the management of HIV-associated cognitive impairment by performing a systematic review of the MEDLINE database using PubMed. We report that, in general, guidelines from around the world regarding the management of HIV-associated cognitive impairment are converging. Screening is generally not recommended in asymptomatic PLWH. Diagnosis of HIV-associated cognitive impairment should be made only after a comprehensive assessment and exclusion of other potential causes. Antiretroviral therapy forms the cornerstone of management of HIV associated cognitive impairment and should be guided by plasma and cerebrospinal fluid (CSF) genotype(s). PMID- 27353599 TI - Erratum for "Safe use of high intakes of folic acid: research challenges and paths forward." Nutrition Reviews 2016; 74: 469-474. PMID- 27353600 TI - Clinical, Ergonomic, and Economic Outcomes With Multichamber Bags Compared With (Hospital) Pharmacy Compounded Bags and Multibottle Systems: A Systematic Literature Review. AB - BACKGROUND: Multichamber bags (MCBs) may offer potential clinical, ergonomic, and economic advantages compared with (hospital) pharmacy compounded bags (COBs) and multibottle systems (MBSs). METHODS: A systematic literature review was performed to identify and assess the available evidence regarding advantages of MCBs compared with COBs and MBSs. Medline, Embase, the Cochrane Databases, and EconLit were searched for articles reporting clinical, ergonomic, and economic outcomes for MCBs compared with COBs or MBSs. The search was limited to studies conducted in hospitalized patients >2 years of age that were published in English between January 1990 and November 2014. The Population Intervention Comparison Outcomes Study Design (PICOS) framework was used for the analysis. RESULTS: From 1307 unique citations, 74 potentially relevant publications were identified; review of references identified 2 additional publications. Among the 76 publications, 18 published studies met the inclusion criteria. Most were retrospective in design. Ten studies reported clinical outcomes, including 1 prospective randomized trial and multiple retrospective analyses that reported a lower risk of bloodstream infection for MCBs compared with other delivery systems. Sixteen studies reported ergonomic and/or economic outcomes; most reported a potential cost benefit for MCBs, with consistent reports of reduced time and labor compared with other systems. The largest cost benefit was observed in studies evaluating total hospitalization costs. CONCLUSIONS: The systematic literature review identified evidence of potential clinical, ergonomic, and economic benefits for MCBs compared with COBs and MBSs; however, methodological factors limited evidence quality. More prospective studies are required to corroborate existing evidence. PMID- 27353601 TI - Measuring rotational diffusion of colloidal spheres with confocal microscopy. AB - We report an experimental method to measure the translational and rotational dynamics of colloidal spheres in three dimensions with confocal microscopy and show that the experimental values reasonably agree with the theoretical values. This method can be extended to study rotational dynamics in concentrated colloidal systems and complex bio-systems. PMID- 27353602 TI - Improving Heart Failure Outcomes in Ambulatory and Community Care: A Scoping Study. AB - Despite a large body of literature testing interventions to improve heart failure care, care is often suboptimal. This scoping study assesses organizational interventions to improve heart failure outcomes in ambulatory settings. Fifty-two studies and systematic reviews assessing multicomponent, self-management support, and eHealth interventions were included. Studies dating from the 1990s demonstrated that multicomponent interventions could reduce hospitalizations, readmissions, mortality, and costs and improve quality of life. Self-management support appeared more effective when included in multicomponent interventions. The independent contribution of eHealth interventions remains unclear. No studies addressed management of comorbidities, geriatric syndromes, frailty, or end of life care. Few studies addressed risk stratification or vulnerable populations. Limited reporting about intervention components, implementation methods, and fidelity presents challenges in adapting this literature to scale interventions. The use of standardized reporting guidelines and study designs that produce more contextual evidence would better enable application of this work in health system redesign. PMID- 27353604 TI - On the non-innocence of "Nacnacs": ligand-based reactivity in beta-diketiminate supported coordination compounds. AB - While beta-diketiminate (BDI or 'nacnac') ligands have been widely adopted to stabilize a wide range of metal ions in multiple oxidation states and coordination numbers, in several occurrences these ligands do not behave as spectators and participate in reactivity. Besides unwanted decomposition processes, BDI redox non-innnocence and unusual metal-ligand cooperative activation of substrates yielding attractive reactivity have been reported. This feature article will provide a comprehensive analysis of the various transformations involving BDI ligand platforms in coordination compounds across the periodic table. PMID- 27353603 TI - Zonulin Regulates Intestinal Permeability and Facilitates Enteric Bacteria Permeation in Coronary Artery Disease. AB - Several studies have reported an association between enteric bacteria and atherosclerosis. Bacterial 16S ribosomal RNA (rRNA) gene belong to Enterobacteriaceae have been detected in atherosclerotic plaques. How intestinal bacteria go into blood is not known. Zonulin reversibly modulate intestinal permeability (IP), the circulating zonulin levels were increased in diabetes, obesity, all of which are risk factors for atherosclerosis. It is unclear whether the circulating zonulin levels were changed in coronary artery disease (CAD) patients and modulate IP. The 16S rRNA gene of bacteria in blood sample was checked by 454 pyrosequencing. The zonulin levels were determined by enzyme linked immunosorbent assay (ELISA) methods. The distribution of zonulin was detected by confocal immunofluorescence microscopy. Bacteria and Caco-2 cell surface micro-structure were checked by transmission electron microscopy. A high diversity of bacterial 16S rRNA gene can be detected in samples from CAD patients, most of them (99.4%) belong to Enterobacteriaceaes, eg. Rahnella. The plasma zonulin levels were significantly higher in CAD patients. Pseudomonas fluorescens exposure significantly increased zonulin expression and decreased IP in a time dependent manner. The elevated zonulin increase IP and may facilitate enteric translocation by disassembling the tight junctions, which might explain the observed high diversity of bacterial 16S rRNA genes in blood samples. PMID- 27353605 TI - Association Between Severe Hypoglycemia and Cardiovascular Disease Risk in Japanese Patients With Type 2 Diabetes. PMID- 27353607 TI - Predicting Outcomes Over Time in Patients With Heart Failure, Left Ventricular Systolic Dysfunction, or Both Following Acute Myocardial Infarction. AB - BACKGROUND: Most studies of risk assessment or stratification in patients with myocardial infarction (MI) have been static and fail to account for the evolving nature of clinical events and care processes. We sought to identify predictors of mortality, cardiovascular death or nonfatal MI, and cardiovascular death or nonfatal heart failure (HF) over time in patients with HF, left ventricular systolic dysfunction, or both post-MI. METHODS AND RESULTS: Using data from the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial, we developed models to estimate the association between patient characteristics and the likelihood of experiencing an event from the time of a follow-up visit until the next visit. The intervals are: hospital arrival to discharge or 14 days, whichever occurs first; hospital discharge to 30 days; 30 days to 6 months; and 6 months to 3 years. Models were also developed to predict the entire 3-year follow-up period using baseline information. Multivariable Cox proportional hazards modeling was used throughout with Wald chi-squares as the comparator of strength for each predictor. For the baseline model of overall mortality, the 3 strongest predictors were age (adjusted hazard ratio [HR], 1.35; 95% CI, 1.28-1.42; P<0.0001), baseline heart rate (adjusted HR, 1.17; 95% CI, 1.14-1.21; P<0.0001), and creatinine clearance (<=100 mL/min; adjusted HR, 0.86; 95% CI, 0.84-0.89; P<0.0001). According to the integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indices, the updated model had significant improvement over the model with baseline covariates only in all follow-up periods and with all outcomes. CONCLUSIONS: Patient information assessed closest to the time of the outcome was more valuable in predicting death when compared with information obtained at the time of the index hospitalization. Using updated patient information improves prognosis over using only the information available at the time of the index event. PMID- 27353606 TI - Outcome of 1051 Octogenarian Patients With ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention: Observational Cohort From the London Heart Attack Group. AB - BACKGROUND: ST-segment elevation myocardial infarction is increasingly common in octogenarians, and optimal management in this cohort is uncertain. This study aimed to describe the outcomes of octogenarians with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention. METHODS AND RESULTS: We analyzed 10 249 consecutive patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention between 2005 and 2011 at 8 tertiary cardiac centers across London, United Kingdom. The primary end point was all-cause mortality at a median follow up of 3 years. In total, 1051 patients (10.3%) were octogenarians, with an average age of 84.2 years, and the proportion increased over the study period (P=0.04). In-hospital mortality (7.7% vs 2.4%, P<0.0001) and long-term mortality (51.6% vs 12.8%, P<0.0001) were increased in octogenarians compared with patients aged <80 years, and age was an independent predictor of mortality in a fully adjusted model (hazard ratio 1.07, 95% CI 1.07-1.09, P<0.0001). Time-stratified analysis revealed an increasingly elderly and more complex cohort over time. Nonetheless, long-term mortality rates among octogenarians remained static over time, and this may be attributable to improved percutaneous coronary intervention techniques, including significantly higher rates of radial access and lower bleeding complications. Variables associated with bleeding complications were similar between octogenarian and younger cohorts. CONCLUSIONS: In this large registry, octogenarians undergoing primary percutaneous coronary intervention had a higher rate of complications and mortality compared with a younger population. Over time, octogenarians undergoing primary percutaneous coronary intervention increased in number, age, and complexity. Nevertheless, in-hospital outcomes were reasonable, and long-term mortality rates were static. PMID- 27353608 TI - Cystatin C Predicts Incident Cardiovascular Disease in Twins. AB - BACKGROUND: Cystatin C is associated with both renal function and atherosclerotic cardiovascular disease (ASCVD). We have previously shown a genetic correlation between cystatin C and prevalent ASCVD. The objective of this article is to study whether variation in cystatin C or creatinine predicts incident ASCVD when controlled for genetic factors. METHODS AND RESULTS: The predictive value of cystatin C and creatinine for incident ASCVD was studied in 11 402 Swedish twins, free of CVD at baseline, in an adjusted Cox-regression model during a median follow-up of 71 months. Twin pairs discordant for incident stroke, myocardial infarction and ASCVD during follow-up were identified and within-pair comparisons regarding cystatin C and creatinine levels were performed. We also investigated whether contact frequency and degree of shared environment influences were associated with similarity in cystatin C levels. In univariate analysis, cystatin C predicted incident ASCVD hazard ratio 1.57, 95% CI 1.47-1.67. When adjusted for traditional Framingham risk factors as covariates, cystatin C remained a predictor of incident stroke hazard ratio 1.45, 95% CI (1.25-1.70), ASCVD hazard ratio 1.26, 95% CI (1.13-1.41), and myocardial infarction hazard ratio 1.16, 95% CI (1.01-1.33). In twins discordant for incident stroke, cystatin C at baseline was higher in the twin who experienced a stroke compared to the healthy co-twin (1.11+/-0.3 mg/L versus 1.06+/-0.3 mg/L), whereas creatinine was lower in the twin who developed CVD compared to their healthy co-twins (76.1+/-16.9 MUmol/L versus 79.4+/-20.3 MUmol/L). CONCLUSIONS: Variation in cystatin C relates to incident ASCVD and to stroke when adjusted for genetic confounding. In identical twins, cystatin C may be a sensitive marker of early hypertensive end-organ damage and small-vessel disease, whereas creatinine level may reflect nutritional status. The findings in disease-discordant monozygotic twins indicate that unique, possibly preventable, environmental factors are important. PMID- 27353609 TI - Inflammatory Markers Associated With Subclinical Coronary Artery Disease: The Multicenter AIDS Cohort Study. AB - BACKGROUND: Despite evidence for higher risk of coronary artery disease among HIV+ individuals, the underlying mechanisms are not well understood. We investigated associations of inflammatory markers with subclinical coronary artery disease in 923 participants of the Multicenter AIDS Cohort Study (575 HIV+ and 348 HIV- men) who underwent noncontrast computed tomography scans for coronary artery calcification, the majority (n=692) also undergoing coronary computed tomography angiography. METHODS AND RESULTS: Outcomes included presence and extent of coronary artery calcification, plus computed tomography angiography analysis of presence, composition, and extent of coronary plaques and severity of coronary stenosis. HIV+ men had significantly higher levels of interleukin-6 (IL 6), intercellular adhesion molecule-1, C-reactive protein, and soluble-tumor necrosis factor-alpha receptor (sTNFalphaR) I and II (all P<0.01) and a higher prevalence of noncalcified plaque (63% versus 54%, P=0.02) on computed tomography angiography. Among HIV+ men, for every SD increase in log-interleukin-6 and log intercellular adhesion molecule-1, there was a 30% and 60% increase, respectively, in the prevalence of coronary stenosis >=50% (all P<0.05). Similarly, sTNFalphaR I and II in HIV+ participants were associated with an increase in prevalence of coronary stenosis >=70% (P<0.05). Higher levels of interleukin-6, sTNFalphaR I, and sTNFalphaR II were also associated with greater coronary artery calcification score in HIV+ men (P<0.01). CONCLUSIONS: Higher inflammatory marker levels are associated with greater prevalence of coronary stenosis in HIV+ men. Our findings underscore the need for further study to elucidate the relationships of inflammatory pathways with coronary artery disease in HIV+ individuals. PMID- 27353611 TI - Knowledge, attitudes and practices regarding human papillomavirus vaccination among young women attending a tertiary institution in Singapore. AB - INTRODUCTION: This study aimed to describe the knowledge, attitudes and practices of young women regarding human papillomavirus (HPV) vaccination. METHODS: We conducted a descriptive, cross-sectional, questionnaire-based study among female students at a tertiary institute in Singapore. RESULTS: A total of 255 questionnaires were completed and formed the basis of the analysis. 244 (95.7%) of the total participants were of the age group 15-22 years. 252 (98.8%) participants were unmarried and 240 (94.1%) had never had sexual intercourse. Only 25 (9.8%) women had received vaccination. Among the unvaccinated participants, 96 (41.7%) had no intention to receive HPV vaccination and 62 of them cited lack of information as a major barrier to HPV vaccination. Knowledge of cervical cancer and HPV vaccination was also assessed and graded via a point system, with a maximum score of 14. Knowledge was found to be low, with a median score of 7. There was a significant association between HPV vaccination uptake and the source from which they first heard about the vaccine (p = 0.007). Vaccinated respondents tended to first hear about it from their relatives and friends, as compared to unvaccinated respondents (60.0% vs. 27.0%). CONCLUSION: There is poor uptake of HPV vaccination amongst Singapore's susceptible youth as well as poor knowledge of cervical cancer and HPV vaccination. Public health education regarding cervical cancer and HPV vaccination is still needed and has to be targeted at not only respondents, but also their family and friends. PMID- 27353610 TI - Postnatal Development of Right Ventricular Myofibrillar Biomechanics in Relation to the Sarcomeric Protein Phenotype in Pediatric Patients with Conotruncal Heart Defects. AB - BACKGROUND: The postnatal development of myofibrillar mechanics, a major determinant of heart function, is unknown in pediatric patients with tetralogy of Fallot and related structural heart defects. We therefore determined the mechanical properties of myofibrils isolated from right ventricular tissue samples from such patients in relation to the developmental changes of the isoforms expression pattern of key sarcomere proteins involved in the contractile process. METHODS AND RESULTS: Tissue samples from the infundibulum obtained during surgery from 25 patients (age range 15 days to 11 years, median 7 months) were split into half for mechanical investigations and expression analysis of titin, myosin heavy and light chain 1, troponin-T, and troponin-I. Of these proteins, fetal isoforms of only myosin light chain 1 (ALC-1) and troponin-I (ssTnI) were highly expressed in neonates, amounting to, respectively, 40% and 80%, while the other proteins had switched to the adult isoforms before or around birth. ALC-1 and ssTnI expression subsequently declined monoexponentially with a halftime of 4.3 and 5.8 months, respectively. Coincident with the expression of ssTnI, Ca(2+) sensitivity of contraction was high in neonates and subsequently declined in parallel with the decline in ssTnI expression. Passive tension positively correlated with Ca(2+) sensitivity but not with titin expression. Contraction kinetics, maximal Ca(2+)-activated force, and the fast phase of the biphasic relaxation positively correlated with the expression of ALC-1. CONCLUSIONS: The developmental changes in myofibrillar biomechanics can be ascribed to fetal-to-adult isoform transition of key sarcomeric proteins, which evolves regardless of the specific congenital cardiac malformations in our pediatric patients. PMID- 27353612 TI - Leading With LARCs in Nigeria: The Stars Are Aligned to Expand Effective Family Planning Services Decisively. PMID- 27353613 TI - A Convenient Truth: Cost of Medications Need Not Be a Barrier to Hepatitis B Treatment. PMID- 27353614 TI - Investing in Family Planning: Key to Achieving the Sustainable Development Goals. PMID- 27353615 TI - mHealth for Tuberculosis Treatment Adherence: A Framework to Guide Ethical Planning, Implementation, and Evaluation. PMID- 27353616 TI - Feasibility and Effectiveness of mHealth for Mobilizing Households for Indoor Residual Spraying to Prevent Malaria: A Case Study in Mali. AB - Components of mHealth are increasingly being added to development interventions worldwide. A particular case of interest is in Mali where the U.S. President's Malaria Initiative (PMI) Africa Indoor Residual Spraying (AIRS) Project piloted a mobile mass-messaging service in Koulikoro District in August 2014 to determine whether voice and/or text messages received on cell phones could effectively replace door-to-door mobilization for an indoor residual spraying (IRS) campaign. To measure the pilot's effectiveness, we evaluated structure preparedness (all household and food items removed) in 3 pilot intervention villages compared with 3 villages prepared for spray through door-to-door mobilization that was modified by incorporating town hall meetings and radio spots. Structure preparedness was significantly lower in households mobilized through the mobile-messaging approach compared with the door-to-door approach (49% vs. 75%, respectively; P = .03). Spray coverage of targeted households also was significantly lower among the mobile-messaging villages than the door-to-door mobilization villages (86% vs. 96%, respectively; P = .02). The mobile-messaging approach, at US$8.62 per structure prepared, was both more costly and less effective than the door-to-door approach at US$1.08 per structure prepared. While literacy and familiarity with technology were major obstacles, it also became clear that by removing the face to-face interactions between mobilizers and household residents, individuals were not as trusting or understanding of the mobilization messages. These residents felt it was easier to ignore a text or voice message than to ignore a mobilizer who could provide reassurances and preparation support. In addition, men often received the mobile messages, as they typically owned the mobile phones, while women-who were more likely to be at home at the time of spray-usually interacted with the door-to-door mobilizers. Future attempts at using mHealth approaches for similar IRS mobilization efforts in Mali should be done in a way that combines mHealth tools with more common human-based interventions, rather than as a stand alone approach, and should be designed with a gender lens in mind. The choice of software used for mass messaging should also be considered to find a local option that is both less expensive and perhaps more attuned to the local context than a U.S.-based software solution. PMID- 27353617 TI - Factors Associated With Community Health Worker Performance Differ by Task in a Multi-Tasked Setting in Rural Zimbabwe. AB - BACKGROUND: Zimbabwe, like most low-income countries, faces health worker shortages. Community health workers (CHWs) bridge this gap by delivering essential health services and nutrition interventions to communities. However, as workloads increase, CHWs' ability to provide quality services may be compromised. We studied influences upon CHWs' performance related to pregnancy surveillance and nutrition and hygiene education in rural Zimbabwe. METHODS: In the context of a cluster-randomized trial conducted in 2 rural districts between November 2012 and March 2015, 342 government-employed CHWs identified and referred pregnant women for early antenatal care and delivered household-level behavior change lessons about infant feeding and hygiene to more than 5,000 women. In 2013, we conducted a survey among 322 of the CHWs to assess the association between demographic and work characteristics and task performance. Exploratory factor analyses of the Likert-type survey questions produced 8 distinct and reliable constructs of job satisfaction and motivation, supervision, peer support, and feedback (Cronbach alpha range, 0.68 to 0.92). Pregnancy surveillance performance was assessed from pregnancy referrals, and nutrition and hygiene education performance was assessed by taking the average summative score (range, 5 to 30) of lesson delivery observations completed by a nurse supervisor using a 6-item Likert-type checklist. Poisson and multiple linear regressions were used to test associations between CHW demographic and work characteristics and performance. RESULTS: CHWs who referred more pregnant women were female, unmarried, under 40 years old, from larger households, and of longer tenure. They also perceived work resources to be adequate and received positive feedback from supervisors and the community, but they were less satisfied with remuneration. CHWs with high scores on behavior change lesson delivery were from smaller households, and they received more supportive supervision but less operational supervision. Measures of job satisfaction and motivation were not associated with either task. CONCLUSION: Among CHWs responsible for multiple tasks in rural Zimbabwe, factors associated with performance of one task were not the same as those associated with performance of another task. Our methods and findings illustrate ways to examine heterogeneity in CHW performance and to identify organizational factors associated with quality of program delivery. PMID- 27353618 TI - School Distribution as Keep-Up Strategy to Maintain Universal Coverage of Long Lasting Insecticidal Nets: Implementation and Results of a Program in Southern Tanzania. AB - Tanzania successfully scaled up coverage of long-lasting insecticidal nets (LLINs) through mass campaigns. To sustain these gains, a school-based approach was piloted in the country's Southern Zone starting in 2013, called the School Net Program 1 (SNP1). We report on the design, implementation, monitoring, and outputs of the second round (SNP2) undertaken in 2014. SNP2 was conducted in all schools in Lindi, Mtwara, and Ruvuma regions, targeting students in primary (Standards 1, 3, 5, and 7) and secondary (Forms 2 and 4) schools and all teachers. In Lindi region, 2 additional classes (Standards 2 and 4) were targeted. LLIN distribution data were managed using an Android software application called SchoolNet. SNP2 included 2,337 schools, 473,700 students, and 25,269 teachers. A total of 5,070 people were trained in LLIN distribution (487 trainers and 4,583 distributors), and 4,392 (434 ward and 3,958 village) community change agents undertook sensitization and mobilization. A total of 507,775 LLINs were distributed to schools, with 464,510 (97.9% of those registered) students and 24,206 (95.8% of those registered) school teachers receiving LLINs. LLIN ownership and use is expected to have increased, potentially further reducing the burden of malaria in the Southern Zone of Tanzania. PMID- 27353619 TI - Improved Childhood Diarrhea Treatment Practices in Ghana: A Pre-Post Evaluation of a Comprehensive Private-Sector Program. AB - Diarrhea is the fourth leading cause of child mortality in Ghana. In 2010, Ghana endorsed guidelines from the World Health Organization and the United Nations Children's Fund for use of zinc with low-osmolarity oral rehydration salts (ORS) for the treatment of acute childhood diarrhea. From late 2011 through 2014, the Strengthening Health Outcomes through the Private Sector (SHOPS) project implemented a comprehensive program in 3 regions of Ghana to increase the availability and use of ORS and zinc and to decrease incorrect use of antibiotics and antidiarrheals. The program included (1) partnering with local pharmaceutical firms to introduce and market locally produced zinc products, (2) collaborating with the Ghanaian Pharmacy Council to provide training and supportive supervision of private-sector providers on diarrhea management, and (3) conducting mass media campaigns to raise caregiver awareness. We evaluated the effect of this program using a baseline survey of 754 caregivers of children under 5 with diarrhea at the start of the intervention in 2012 and a follow-up survey of 751 caregivers in 2014. Regression analysis showed that use of ORS with zinc increased from 0.8% in 2012 to 29.2% in 2014 (P<.001), and antibiotic use declined from 66.2% to 38.2% (P<.001) during the same period. The magnitude and statistical significance of these results remained the same after including potential confounding factors as covariates. Inappropriate antibiotic use, however, remained high at follow-up. We conclude that similar programs applied in other settings have the potential to rapidly scale up use of ORS and zinc. Additional efforts are required to reduce persistent incorrect antibiotic use. PMID- 27353620 TI - Success Providing Postpartum Intrauterine Devices in Private-Sector Health Care Facilities in Nigeria: Factors Associated With Uptake. AB - BACKGROUND: Use of modern contraceptive methods in Nigeria remained at 10% between 2008 and 2013 despite substantive investments in family planning services. Many women in their first postpartum year, in particular, have an unmet need for family planning. We evaluated use of postpartum intrauterine device (IUD) insertion and determined factors associated with its uptake in Nigeria. METHODS: Data were collected between May 2014 and February 2015 from 11 private health care facilities in 6 southern Nigerian states. Women attending antenatal care in participating facilities were counseled on all available contraceptive methods including the postpartum IUD. Data were abstracted from participating facility records and evaluated using a cross-sectional analysis. Categorical variables were calculated as proportions while continuous variables were calculated as medians with the associated interquartile range (IQR). Multivariate logistic regression analysis was used to identify factors associated with uptake of the postpartum IUD while controlling for potential confounding factors, including age, educational attainment, marital status, parity, number of living children, and previous use of contraception. RESULTS: During the study period, 728 women delivered in the 11 facilities. The median age was 28 years, and most women were educated (73% had completed at least the secondary level). The majority (96%) of the women reported they were married, and the median number of living children was 3 (IQR, 2-4). Uptake of the postpartum IUD was 41% (n = 300), with 8% (n = 25) of the acceptors experiencing expulsion of the IUD within 6 weeks post-insertion. After controlling for potential confounding factors, several characteristics were associated with greater likelihood of choosing the postpartum IUD, including lower education, having a higher number of living children, and being single. Women who had used contraceptives previously were less likely to choose the postpartum IUD than women who had not previously used contraception (adjusted odds ratio, 0.68; 95% confidence interval, 0.55 to 0.84). CONCLUSION: A high percentage (41%) of women delivering in private health care facilities in southern Nigeria accepted immediate postpartum IUD insertion. Scale up of postpartum IUD services is a promising approach to increasing uptake of long-acting reversible contraceptives among women in Nigeria. PMID- 27353621 TI - Partnerships for Policy Development: A Case Study From Uganda's Costed Implementation Plan for Family Planning. AB - In global health, partnerships between practitioners and policy makers facilitate stakeholders in jointly addressing those issues that require multiple perspectives for developing, implementing, and evaluating plans, strategies, and programs. For family planning, costed implementation plans (CIPs) are developed through a strategic government-led consultative process that results in a detailed plan for program activities and an estimate of the funding required to achieve an established set of goals. Since 2009, many countries have developed CIPs. Conventionally, the CIP approach has not been defined with partnerships as a focal point; nevertheless, cooperation between key stakeholders is vital to CIP development and execution. Uganda launched a CIP in November 2014, thus providing an opportunity to examine the process through a partnership lens. This article describes Uganda's CIP development process in detail, grounded in a framework for assessing partnerships, and provides the findings from 22 key informant interviews. Findings reveal strengths in Uganda's CIP development process, such as willingness to adapt and strong senior management support. However, the evaluation also highlighted challenges, including district health officers (DHOs), who are a key group of implementers, feeling excluded from the development process. There was also a lack of planning around long-term partnership practices that could help address anticipated execution challenges. The authors recommend that future CIP development efforts use a long-term partnership strategy that fosters accountability by encompassing both the short term goal of developing the CIP and the longer-term goal of achieving the CIP objectives. Although this study focused on Uganda's CIP for family planning, its lessons have implications for any policy or strategy development efforts that require multiple stakeholders to ensure successful execution. PMID- 27353622 TI - Family Planning Counseling in Your Pocket: A Mobile Job Aid for Community Health Workers in Tanzania. AB - To address low contraceptive use in Tanzania, a pilot intervention using a mobile job aid was developed to guide community health workers (CHWs) to deliver integrated counseling on family planning, HIV, and other sexually transmitted infections (STIs). In this article, we describe the process of developing the family planning algorithms and implementation of the mobile job aid, discuss how the job aid supported collection of real-time data for decision making, and present the cost of the overall system based on an evaluation of the pilot. The family planning algorithm was developed, beginning in June 2011, in partnership with the Tanzania Ministry of Health and Social Welfare based on a combination of evidence-based tools such as the Balanced Counseling Strategy Plus Toolkit. The pilot intervention and study was implemented with 25 CHWs in 3 wards in Ilala district in Dar es Salaam between January 2013 and July 2013. A total of 710 family planning users (455 continuing users and 255 new users) were registered and counseled using the mobile job aid over the 6-month intervention period. All users were screened for current pregnancy, questioned on partner support for contraceptive use, counseled on a range of contraceptives, and screened for HIV/STI risk. Most new and continuing family planning users chose pills and male condoms (59% and 73%, respectively). Pills and condoms were provided by the CHW at the community level. Referrals were made to the health facility for pregnancy confirmation, injectable contraceptives, long-acting reversible contraceptives and HIV/STI testing. Follow-up visits with clients were planned to confirm completion of the health facility referral. The financial cost of implementing this intervention with 25 CHWs and 3 supervisors are estimated to be US$26,000 for the first year. For subsequent years, the financial costs are estimated to be 73% lower at $7,100. Challenges such as limited client follow-up by CHWs and use of data by supervisors identified during the pilot are currently being addressed during the scale-up phase by developing accountability and incentive mechanisms for CHWs and dashboards for data access and use. PMID- 27353623 TI - Enhancing the Supervision of Community Health Workers With WhatsApp Mobile Messaging: Qualitative Findings From 2 Low-Resource Settings in Kenya. AB - An estimated half of all mobile phone users in Kenya use WhatsApp, an instant messaging platform that provides users an affordable way to send and receive text messages, photos, and other media at the one-to-one, one-to-many, many-to-one, or many-to-many levels. A mobile learning intervention aimed at strengthening supervisory support for community health workers (CHWs) in Kibera and Makueni, Kenya, created a WhatsApp group for CHWs and their supervisors to support supervision, professional development, and team building. We analyzed 6 months of WhatsApp chat logs (from August 19, 2014, to March 1, 2015) and conducted interviews with CHWs and their supervisors to understand how they used this instant messaging tool. During the study period, 1,830 posts were made by 41participants. Photos were a key component of the communication among CHWs and their supervisors: 430 (23.4%) of all posts contained photos or other media. Of the remaining 1,400 text-based posts, 87.6% (n = 1,227) related to at least 1 of 3 defined supervision objectives: (1) quality assurance, (2) communication and information, or (3) supportive environment. This supervision took place in the context of posts about the roll out of the new mobile learning intervention and the delivery of routine health care services, as well as team-building efforts and community development. Our preliminary investigation demonstrates that with minimal training, CHWs and their supervisors tailored the multi-way communication features of this mobile instant messaging technology to enact virtual one-to-one, group, and peer-to-peer forms of supervision and support, and they switched channels of communication depending on the supervisory objectives. We encourage additional research on how health workers incorporate mobile technologies into their practices to develop and implement effective supervisory systems that will safeguard patient privacy, strengthen the formal health system, and create innovative forms of community-based, digitally supported professional development for CHWs. PMID- 27353624 TI - Declining HIV Prevalence in Parallel With Safer Sex Behaviors in Burkina Faso: Evidence From Surveillance and Population-Based Surveys. AB - OBJECTIVE: To investigate trends in HIV prevalence and changes in reported sexual behaviors between 1998 and 2014 in Burkina Faso. METHODS: We obtained data on HIV prevalence from antenatal care (ANC) surveillance sites (N = 9) that were consistently included in surveillance between 1998 and 2014. We also analyzed data on HIV prevalence and reported sex behaviors from 3 population-based surveys from the Demographic and Health Surveys (DHS), conducted in 1998-99, 2003, and 2010. Sex behavior indicators comprised never-married youth who have never had sex; sex with more than 1 partner; sex with a nonmarital, non-cohabiting partner; condom use at last sex with a nonmarital, non-cohabiting partner; and sex before age 15. We calculated survey-specific HIV prevalence with 95% confidence intervals (CIs) and used the chi-square test or chi-square test for trend to compare HIV prevalence across survey years and to analyze trends in reported sex behaviors. RESULTS: HIV prevalence among pregnant women ages 15-49 decreased by 72% in urban areas, from 7.1% in 1998 to 2.0% in 2014, and by 75% in rural areas, from 2.0% in 2003 to 0.5% in 2014. HIV declined most in younger age groups, which is a good reflection of recent incidence, with declines of 55% among 15-19-year olds, 72% among 20-24-year-olds, 40% among 25-29-year-olds, and 7% among those >=30 years old (considering urban and rural data combined). Data reported in the DHS corroborated these declines in HIV prevalence: between 2003 and 2010, HIV prevalence dropped significantly-by 89% among girls ages 15-19, from 0.9% (95% CI, 0.2 to 1.6) to 0.1% (95% CI, 0.0 to 0.4), and by 78% among young women ages 20-24, from 1.8% (95% CI, 1.6 to 3.0) to 0.4% (95% CI, 0.0 to 0.7). During the same time period, people reported safer sex behaviors. For example, significantly higher percentages of never-married youth reported they had never had sex, lower percentages of sexually active youth reported multiple sex partners, and lower percentages of youth reported having sex before age 15. In addition, the percentage of men ages 20-49 reporting sex with a nonmarital, non-cohabiting partner declined significantly, while condom use at last sex with such a partner increased significantly among both men and women ages 15-49. CONCLUSIONS: Both ANC surveillance and population-based surveys report sharp declines in HIV prevalence in Burkina Faso between 1998 and 2014, accompanied by improvements in reported risky sex behaviors. PMID- 27353625 TI - Handwashing With a Water-Efficient Tap and Low-Cost Foaming Soap: The Povu Poa "Cool Foam" System in Kenya. PMID- 27353626 TI - Fertility Awareness Methods Are Not Modern Contraceptives: Defining Contraception to Reflect Our Priorities. PMID- 27353627 TI - Response to Austad: Offering a Range of Methods, Including Fertility Awareness Methods, Facilitates Method Choice. PMID- 27353628 TI - Perinatal Mortality Due to Pre-Eclampsia in Africa: A Comprehensive and Integrated Approach Is Needed. PMID- 27353629 TI - Editors' Response to Omotayo: Research Needed on Better Prevention of Pre Eclampsia. PMID- 27353630 TI - Optimism for the UN Proclamation of the Decade of Action on Nutrition: An African Perspective. PMID- 27353632 TI - Holographic microscopy and microfluidics platform for measuring wall stress and 3D flow over surfaces textured by micro-pillars. AB - Understanding how fluid flow interacts with micro-textured surfaces is crucial for a broad range of key biological processes and engineering applications including particle dispersion, pathogenic infections, and drag manipulation by surface topology. We use high-speed digital holographic microscopy (DHM) in combination with a correlation based de-noising algorithm to overcome the optical interference generated by surface roughness and to capture a large number of 3D particle trajectories in a microfluidic channel with one surface patterned with micropillars. It allows us to obtain a 3D ensembled velocity field with an uncertainty of 0.06% and 2D wall shear stress distribution at the resolution of ~65 MUPa. Contrary to laminar flow in most microfluidics, we find that the flow is three-dimensional and complex for the textured microchannel. While the micropillars affect the velocity flow field locally, their presence is felt globally in terms of wall shear stresses at the channel walls. These findings imply that micro-scale mixing and wall stress sensing/manipulation can be achieved through hydro-dynamically smooth but topologically rough micropillars. PMID- 27353633 TI - Human choices between variable and fixed rewards in hypothetical variable-delay and double-reward discounting procedures. AB - Prior research has shown that nonhumans show an extreme preference for variable- over fixed-delays to reinforcement. This well-established preference for variability occurs because a reinforcer's strength or "value" decreases according to a curvilinear function as its delay increases. The purpose of the present experiments was to investigate whether this preference for variability occurs with human participants making hypothetical choices. In three experiments, participants recruited from Amazon Mechanical Turk made choices between variable and fixed monetary rewards. In a variable-delay procedure, participants repeatedly chose between a reward delivered either immediately or after a delay (with equal probability) and a reward after a fixed delay (Experiments 1 and 2). In a double-reward procedure, participants made choices between an alternative consisting of two rewards, one delivered immediately and one after a delay, and a second alternative consisting of a single reward delivered after a delay (Experiments 1 and 3). Finally, all participants completed a standard delay discounting task. Although we observed both curvilinear discounting and magnitude effects in the standard discounting task, we found no consistent evidence of a preference for variability-as predicted by two prominent models of curvilinear discounting (i.e., a simple hyperbola and a hyperboloid)-in our variable-delay and double-reward procedures. This failure to observe a preference for variability may be attributed to the hypothetical, rule-governed nature of choices in the present study. In such contexts, participants may adopt relatively simple strategies for making more complex choices. PMID- 27353634 TI - Comparison of laparoscopic liver resection for hepatocellular carcinoma located in the posterosuperior segments or anterolateral segments: A case-matched analysis. AB - BACKGROUND: Laparoscopic liver resection is an attractive option for treating liver tumors. Laparoscopic liver resection is more difficult for hepatocellular carcinomas located in the posterosuperior segments than for hepatocellular carcinomas in the anterolateral segments. We compared perioperative and long-term outcomes between laparoscopic liver resection for hepatocellular carcinomas located in the posterosuperior and anterolateral segments. METHODS: We retrospectively reviewed the clinical data for 230 patients who underwent laparoscopic liver resection for hepatocellular carcinomas between September 2003 and July 2014. Of these, 116 patients were selected by case-matched analysis using age, sex, tumor number and size, Child-Pugh class, and extent of liver resection. Patients were classified into 2 groups according to tumor location: the anterolateral group (n = 58) and the posterosuperior group (n = 58). RESULTS: Operation time (355 minutes vs 212 minutes, P < .005), intraoperative blood loss (600 mL vs 410 mL, P < .001), and hospital stay (8.5 days vs 7 days, P = .040) were significantly greater in the posterosuperior group than in the anterolateral group. The open conversion (13.8% vs 10.3%, P = .777), postoperative complication (17.2% vs 10.3%, P = .420), 5-year overall survival (88.5% vs 85.7%, P = .370), and 5-year, recurrence-free survival (47.6% vs 40.9%, P = .678) rates were not significantly different between the posterosuperior and anterolateral groups. CONCLUSION: Although laparoscopic liver resection is more difficult for hepatocellular carcinomas located in the posterosuperior segment, there were no differences in the short- and long-term outcomes between the posterosuperior and anterolateral groups. The perceived impact of tumor location on patient outcomes could be overcome by experience and technical improvements. PMID- 27353635 TI - Optimum coil insertion speed of various coils in brain aneurysm embolization in vitro. AB - A coil must comprise material with shape memory to perform optimal coil embolization. To achieve this, the alloy characteristics of the coil (hardness, shape, and thickness) must be understood. In this experiment, a catheter was fixed in the bright position and the movement of the coil was observed under a constant rate of insertion; the optimal insertion rate during clinical use was investigated. The first coil insertion speed was evaluated using simulated aneurysms in an in vivo arterial model. The results showed that the insertion force relates to the deployment shape of the coil, that the feedback through the force indicator using sound is very effective, and that the recorder is useful for analysis of coil embolization. The inserted coils during aneurysm embolization were able to wind uniformly within the aneurysm due to a variety of factors (guiding or micro-catheter position and kick-back phenomenon such as delivery wire). Optimal speed is achieved with proper coil design, which allows the coil to be inserted into the aneurysm. The shape and size of the aneurysm can help determine the necessary size and design of the coil that should be used during the optimal speed range. Aneurysm wall and coil characteristics are considered, along with the friction state of the coil (hardness, shape, and thickness), leading to improvements in safety during the insertion procedure at optimum speed. PMID- 27353636 TI - Intestinal malrotation needs immediate consideration and investigation. AB - BACKGROUND: The aim of this study was to evaluate clinical presentation, diagnostic studies, and volvulus rate and to describe the unusual clinical clues of intestinal malrotation. METHODS: A retrospective descriptive review was carried out of all patients diagnosed with intestinal malrotation between 2002 and 2014. Patients were divided into two groups: infants (<=1 year, n = 16; group 1); and children (>1 year, n = 12; group 2). Patient demographics, clinical history, symptoms, physical examination, diagnostic work-up, operative findings and early outcome were evaluated. RESULTS: Bilious vomiting was the cardinal complaint in both groups. Unusual symptoms such as respiratory insufficiency, dehydration, afebrile convulsion, and lethargy were prominent symptoms in six patients in group 1, whereas history of frequent hospitalization due to recurrent abdominal pain and feeding intolerance were prominent in six patients in group 2. Midgut volvulus was identified in 15 patients, four of whom were in group 2. Standard Ladd's procedure was done in addition to correction of volvulus. CONCLUSION: Malrotation with or without midgut volvulus is not a rare condition and should be kept in mind for any age group. Specific signs of diagnosis are not easily identified. In the case of unusual clinical presentation, diagnosis may be delayed and can result in catastrophic consequences if intestinal perfusion occurs. Although midgut volvulus is seen most frequently in infants, risk and complication rate are high beyond 1 year of age as well, and can manifest as failure to thrive, food intolerance, and abdominal pain needing recurrent hospitalization. Diagnostic suspicion and interdisciplinary coordination are essential for timely diagnosis and surgical treatment. PMID- 27353637 TI - Advances in understanding the pathogenesis of the red cell volume disorders. AB - Genetic defects of erythrocyte transport proteins cause disorders of red blood cell volume that are characterized by abnormal permeability to the cations Na(+) and K(+) and, consequently, by changes in red cell hydration. Clinically, these disorders are associated with chronic haemolytic anaemia of variable severity and significant co-morbidities, such as iron overload. This review provides an overview of recent insights into the molecular basis of this group of rare anaemias involving cation channels and transporters dysfunction. To date, a total of 5 different membrane proteins have been reported to be responsible for volume homeostasis alteration when mutated, 3 of them leading to overhydrated cells (AE1 [also termed SLC4A1], RHAG and GLUT1 [also termed SCL2A1) and 2 others to dehydrated cells (PIEZO1 and the Gardos Channel). These findings are not only of basic scientific interest, but also of direct clinical significance for improving diagnostic procedures and identify potential approaches for novel therapeutic strategies. PMID- 27353631 TI - Hydrogenase Enzymes and Their Synthetic Models: The Role of Metal Hydrides. AB - Hydrogenase enzymes efficiently process H2 and protons at organometallic FeFe, NiFe, or Fe active sites. Synthetic modeling of the many H2ase states has provided insight into H2ase structure and mechanism, as well as afforded catalysts for the H2 energy vector. Particularly important are hydride-bearing states, with synthetic hydride analogues now known for each hydrogenase class. These hydrides are typically prepared by protonation of low-valent cores. Examples of FeFe and NiFe hydrides derived from H2 have also been prepared. Such chemistry is more developed than mimicry of the redox-inactive monoFe enzyme, although functional models of the latter are now emerging. Advances in physical and theoretical characterization of H2ase enzymes and synthetic models have proven key to the study of hydrides in particular, and will guide modeling efforts toward more robust and active species optimized for practical applications. PMID- 27353639 TI - Design and synthesis of hollow NiCo2O4 nanoboxes as anodes for lithium-ion and sodium-ion batteries. AB - Hollow porous NiCo2O4-nanoboxes (NCO-NBs) were synthesized with zeolitic imidazolate framework-67 (ZIF-67) nanocrystals as the template followed by a subsequent annealing treatment. The structure and morphology of the NCO-NBs were characterized using X-ray diffraction, field emission scanning electron microscopy and transmission electron microscopy. When tested as potential anode materials for lithium-ion batteries, these porous NCO-NBs with a well-defined hollow structure manifested enhanced performance of Li storage. The discharge capacity of the NCO-NBs remained 1080 mA h g(-1) after 150 cycles at a current rate of 500 mA g(-1) and 884 mA h g(-1) could be obtained at a current density of 2000 mA g(-1) after 200 cycles. Even when cycled at a high density of 8000 mA g( 1), a comparable capacity of 630 mA h g(-1) could be achieved. Meanwhile, the Na storage behavior of NCO-NBs as anode materials of sodium ion batteries (SIBs) was initially investigated and they exhibited a high initial discharge capacity of 826 mA h g(-1), and a moderate capacity retention of 328 mA h g(-1) was retained after 30 cycles. The improved electrochemical performance for NCO-NBs could be attributed to the hierarchical hollow structure and the desirable composition, which provide enough space to alleviate volume expansion during the Li(+)/Na(+) insertion/extraction process and facilitate rapid transport of ions and electrons. PMID- 27353638 TI - Impact of age, gender and CYP2C9/2C19 genotypes on dose-adjusted steady-state serum concentrations of valproic acid-a large-scale study based on naturalistic therapeutic drug monitoring data. AB - PURPOSE: Valproic acid (VPA) has an extensive interindividual pharmacokinetic variability. Published data regarding the impact of gender, age, and CYP2C9/2C19 genetics on VPA variability are conflicting, and the purpose of present study is to clarify the effect of these factors on dose-adjusted steady-state serum VPA concentration (C:D ratio) in a large, naturalistic patient material. METHODS: In patients who had been subjected to cytochrome P450 (CYP) genotyping and therapeutic drug monitoring of VPA, information about serum concentrations, dose, gender, age, and CYP2C9/2C19 genotypes was retrospectively collected from a routine TDM database during the period 2008-2012. The effects of age, gender, and CYP2C9/CYP2C19 genotypes on C:D ratios of VPA were investigated by multivariate analyses (mixed model) including sampling time as covariate. RESULTS: In total, 857 serum concentrations from 252 patients were included. A significant gender effect was observed with a 1.3-fold higher estimated C:D ratio in females than in males, i.e., geometric means 0.34 vs. 0.27 MUM/mg/day, respectively (p < 0.001). A similar and significant difference in estimated geometric means was found between patients >65 vs. <=65 years, i.e., 0.36 vs. 0.26 MUM/mg/day (p < 0.001), respectively. Finally, no association between the various CYP2C9/2C19 variant genotypes and C:D ratio of VPA was observed (p > 0.1). CONCLUSION: The present study shows that age and gender significantly influence VPA serum concentration. In order to obtain similar drug exposure, our findings suggest that older female patients would generally require 30-50 % lower dosing of VPA compared to younger males. Moreover, we conclude that CYP2C9/2C19 genotype is not relevant for variability in VPA exposure. PMID- 27353640 TI - Construct Validity of Almutairi's Critical Cultural Competence Scale. AB - Cultural diversity in health care settings can threaten the well-being of patients, their families, and health care providers. This psychometric study evaluated the construct validity of the recently developed four-factor, 43-item Critical Cultural Competence Scale (CCCS) which was designed to overcome the conceptual limitations of previously developed scales. The study was conducted in Canada with a random sample of 170 registered nurses. Comparisons with the Cultural Competence Assessment instrument, Scale of Ethnocultural Empathy, and Cultural Intelligence Scale provided mixed evidence of convergent validity. Modest correlations were found between the total scale scores suggesting that the CCCS is measuring a more comprehensive and conceptually distinct construct. Stronger correlations were found between the more conceptually similar subscales. Evidence for discriminant validity was also mixed. Results support use of the CCCS to measure health care providers' perceptions of their critical cultural competence though ongoing evaluation is warranted. PMID- 27353641 TI - Social Support and Cognition: Early Childhood Versus Older Adulthood. AB - Cognitive development in early childhood and cognitive preservation in older adulthood are critical for leading healthy life. Social engagement can significantly affect cognition, but their relationships are unclear. The purpose of this review was to synthesize current findings on the relationship between social engagement and cognition in early childhood and older adulthood. PubMed, Web of Science, Ovid Medline, and PsycINFO were searched for studies published in 1995-2015 for a comprehensive review. Included in this review were 42 articles written in English, published in peer-reviewed journals with participants' age being 2 to 6 or >=65 years, and measurement of social engagement and cognition. Overall, greater social engagement was associated with higher levels of cognition across the life span, association of which seemed more prominent in populations at risk of cognitive impairment. Additional research is needed to elucidate biobehavioral mechanisms underlying these relationships and to test the efficacy of new interventions. PMID- 27353642 TI - Green tea extract catechin improves internal cardiac muscle relaxation in RCM mice. AB - BACKGROUND: Diastolic dysfunction refers to an impaired relaxation and an abnormality in a heart's filling during diastole while left ventricular systolic function is preserved. Diastolic dysfunction is commonly observed in patients with primary hypertension, diabetes and cardiomyopathies such as hypertrophic cardiomyopathy or restrictive cardiomyopathy. We have generated a restrictive cardiomyopathy (RCM) mouse model with troponin mutations in the heart to mimic the human RCM patients carrying the same mutations. RESULTS: In the present study, we have investigated the ventricular muscle internal dynamics and pressure developed during systole and diastole by inserting a micro-catheter into the left ventricle of the RCM mice with or without treatment of desensitizer green tea extracts catechins. Our results demonstrate that green tea catechin is able to correct diastolic dysfunction in RCM mainly by improving ventricular compliance and reducing the internal muscle rigidity caused by myofibril hypersensitivity to Ca(2+). CONCLUSION: Green tea extract catechin is effective in correcting diastolic dysfunction and improving ventricular muscle intrinsic compliance in RCM caused by troponin mutations. PMID- 27353643 TI - Seasonality of sex ratio at births in Iceland and effects of the 2010 Eyjafjallajokull volcanic eruption. PMID- 27353644 TI - Urinary inflammatory cytokines as indicators of kidney damage in type 2 diabetic patients. AB - BACKGROUND: The aim of this study was to investigate whether urinary levels of interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are altered in normoalbuminuric patients with type 2 diabetes mellitus (T2DM), and whether these cytokines are able to identify diabetic kidney disease (DKD) among these patients. METHODS: This study included 125 T2DM patients classified into 3 groups according to urinary albumin/creatinine ratio (uACR): uACR <10mg/g creatinine, uACR 10-30mg/g creatinine and uACR >30mg/g creatinine. Urinary inflammatory cytokines were measured. RESULTS: The urinary IL-6 concentrations increased from uACR <10 (97.2+/-26.4pg/ml) to uACR 10-30 (113.6+/-28.0pg/ml) and to uACR >30mg/g creatinine (163.5+/-25.6pg/ml) (P<0.05 and P<0.001, respectively) patients. The urinary IL-10 concentrations decreased in these uACR ranges [100.0 (58.0-141.0) pg/ml vs. 62.0 (54.5-71.5) pg/ml vs. 42.0 (32.0-48.0) pg/ml] (P<0.05 and P<0.001, respectively). All urinary cytokines demonstrated good ability to identify DKD (areas under curves >0.9). CONCLUSIONS: Urinary inflammatory cytokines, especially IL-6 and IL-10, may assist in the identification of DKD in T2DM patients, even in the absence of micro- and macroalbuminuria. PMID- 27353645 TI - A FBN1 mutation association with different phenotypes of Marfan syndrome in a Chinese family. AB - BACKGROUND: Previous studies demonstrated that patients with different FBN1 mutations often present more considerable phenotypic variation compared to different members of the related family carrying a same mutation. The purpose of our study was to identify pathogenic mutation and provide more information about genotype-phenotypic correlations in a large Chinese family with Marfan syndrome. METHODS: 15 related family members from a Chinese 4-generation pedigree with Marfan syndrome underwent physical, ophthalmologic, radiological and cardiovascular examinations. The propositus has De Bakey III aortic dissection and didn't fulfill the revised Ghent criteria for Marfan syndrome. Nine family members have ectopia lentis and their echocardiogram was normal. Five other family members have no evidence of Marfan syndrome. Genomic DNA was isolated from blood leukocytes. The exome sequencing was employed on the propositus, then the Sanger sequencing was conducted for mutation verification in other 14 participants of this family. RESULTS: The causative mutation in FBN1 discovered in the propositus was a known heterozygous missense mutation, c.1633T>G (p.R545C), in exon 14 (NM 000138). This same mutation was also identified in all 9 ectopia lentis patients and one unaffected 8-year-old girl. However, the same mutation was not discovered in other 4 unaffected family members. CONCLUSIONS: Our data enhance the information of genotype-phenotype correlation owing to FBN1 mutations. To our current knowledge, we firstly reported that the same FBN1 mutation, c. 1633C>T (Arg545Cys), was detected simultaneously in three different cardinal phenotypes (ectopia lentis, aortic dissection and unaffected) within one family. The unaffected girl with FBN1 mutation may presumably represent a rare case of nonpenetrance. PMID- 27353646 TI - Presepsin is an early monitoring biomarker for predicting clinical outcome in patients with sepsis. AB - Despite their undoubted helpfulness in diagnosing sepsis, increased blood C reactive protein (CRP) and procalcitonin (PCT) levels have been described in many noninfectious conditions. Presepsin is a soluble fragment of the cluster of differentiation 14 involved in pathogen recognition by innate immunity. We aimed to investigate the diagnostic and prognostic performance of presepsin in comparison to PCT and CRP in patients presenting with systemic inflammatory response syndrome (SIRS) and suspected sepsis. Seventy-six subjects were enrolled in this study, including 51 patients with SIRS as well as 25 healthy subjects. Plasma presepsin, PCT and CRP levels were serially measured on admission and at days 1, 3, 7 and 15. Presepsin and PCT yielded similar diagnostic accuracy, whereas presepsin performed significantly better than CRP. Presepsin and PCT showed comparable performance for predicting 28-day mortality, and both biomarkers performed significantly better than CRP. In septic patients, presepsin revealed earlier concentration changes over time when compared to PCT and CRP. Presepsin and PCT could differentiate between septic and non-septic patients with comparable accuracy and both biomarkers showed similar performance for predicting 28-day mortality. Early changes in presepsin concentrations might reflect the appropriateness of the therapeutic modality and could be useful for making effective treatment decisions. PMID- 27353647 TI - The infectious BAC genomic DNA expression library: a high capacity vector system for functional genomics. AB - Gene dosage plays a critical role in a range of cellular phenotypes, yet most cellular expression systems use heterologous cDNA-based vectors which express proteins well above physiological levels. In contrast, genomic DNA expression vectors generate physiologically-relevant levels of gene expression by carrying the whole genomic DNA locus of a gene including its regulatory elements. Here we describe the first genomic DNA expression library generated using the high capacity herpes simplex virus-1 amplicon technology to deliver bacterial artificial chromosomes (BACs) into cells by viral transduction. The infectious BAC (iBAC) library contains 184,320 clones with an average insert size of 134.5 kb. We show in a Chinese hamster ovary (CHO) disease model cell line and mouse embryonic stem (ES) cells that this library can be used for genetic rescue studies in a range of contexts including the physiological restoration of Ldlr deficiency, and viral receptor expression. The iBAC library represents an important new genetic analysis tool openly available to the research community. PMID- 27353648 TI - The Bacterial Microbiome and Virome Milestones of Infant Development. AB - The human gut harbors a complex community of bacteria, viruses, fungi, protists, and other microorganisms (collectively termed the microbiome) that impact health and disease. Emerging studies indicate that the gut bacterial microbiome and virome play an important role in healthy infant development. In turn, the composition of the microbiome during development can be influenced by factors such as dietary, environmental, and maternal conditions. As such, the microbiome trajectory during early infancy could be predictors of healthy development. Conversely, adverse early events in life may have consequences later in life. This review focuses on our understanding of the bacterial microbiome and virome during early development, conditions that might influence these processes, and their long-term implications for infant health. PMID- 27353649 TI - The Escherichia coli P and Type 1 Pilus Assembly Chaperones PapD and FimC Are Monomeric in Solution. AB - The chaperone/usher pathway is used by Gram-negative bacteria to assemble adhesive surface structures known as pili or fimbriae. Uropathogenic strains of Escherichia coli use this pathway to assemble P and type 1 pili, which facilitate colonization of the kidney and bladder, respectively. Pilus assembly requires a periplasmic chaperone and outer membrane protein termed the usher. The chaperone allows folding of pilus subunits and escorts the subunits to the usher for polymerization into pili and secretion to the cell surface. Based on previous structures of mutant versions of the P pilus chaperone PapD, it was suggested that the chaperone dimerizes in the periplasm as a self-capping mechanism. Such dimerization is counterintuitive because the chaperone G1 strand, important for chaperone-subunit interaction, is buried at the dimer interface. Here, we show that the wild-type PapD chaperone also forms a dimer in the crystal lattice; however, the dimer interface is different from the previously solved structures. In contrast to the crystal structures, we found that both PapD and the type 1 pilus chaperone, FimC, are monomeric in solution. Our findings indicate that pilus chaperones do not sequester their G1 beta-strand by forming a dimer. Instead, the chaperones may expose their G1 strand for facile interaction with pilus subunits. We also found that the type 1 pilus adhesin, FimH, is flexible in solution while in complex with its chaperone, whereas the P pilus adhesin, PapGII, is rigid. Our study clarifies a crucial step in pilus biogenesis and reveals pilus-specific differences that may relate to biological function. IMPORTANCE: Pili are critical virulence factors for many bacterial pathogens. Uropathogenic E. coli relies on P and type 1 pili assembled by the chaperone/usher pathway to adhere to the urinary tract and establish infection. Studying pilus assembly is important for understanding mechanisms of protein secretion, as well as for identifying points for therapeutic intervention. Pilus biogenesis is a multistep process. This work investigates the oligomeric state of the pilus chaperone in the periplasm, which is important for understanding early assembly events. Our work unambiguously demonstrates that both PapD and FimC chaperones are monomeric in solution. We further demonstrate that the solution behavior of the FimH and PapGII adhesins differ, which may be related to functional differences between the two pilus systems. PMID- 27353650 TI - Competence for Genetic Transformation in Streptococcus pneumoniae: Mutations in sigmaA Bypass the ComW Requirement for Late Gene Expression. AB - Streptococcus pneumoniae is able to integrate exogenous DNA into its genome by natural genetic transformation. Transient accumulation of high levels of the only S. pneumoniae alternative sigma factor is insufficient for development of full competence without expression of a second competence-specific protein, ComW. The DeltacomW mutant is 10(4)-fold deficient in the yield of recombinants, 10-fold deficient in the amount of sigma(X) activity, and 10-fold deficient in the amount of sigma(X) protein. The critical role of ComW during transformation can be partially obviated by sigma(A) mutations clustered on surfaces controlling affinity for core RNA polymerase (RNAP). While strains harboring sigma(A) mutations in the comW mutant background were transforming at higher rates, the mechanism of transformation restoration was not clear. To investigate the mechanism of transformation restoration, we measured late gene expression in sigma(A)* suppressor strains. Restoration of late gene expression was observed in DeltacomW sigma(A)* mutants, indicating that a consequence of the sigma(A)* mutations is, at least, to restore sigma(X) activity. Competence kinetics were normal in DeltacomW sigma(A)* strains, indicating that strains with restored competence exhibit the same pattern of transience as wild-type (WT) strains. We also identified a direct interaction between ComW and sigma(X) using the yeast two-hybrid (Y2H) assay. Taken together, these data are consistent with the idea that ComW increases sigma(X) access to core RNAP, pointing to a direct role of ComW in sigma factor exchange during genetic transformation. However, the lack of late gene shutoff in DeltacomW mutants also points to a potential new role for ComW in competence shutoff. IMPORTANCE: The sole alternative sigma factor of the streptococci, SigX, regulates development of competence for genetic transformation, a widespread mechanism of adaptation by horizontal gene transfer in this genus. The transient appearance of this sigma factor is strictly controlled at the levels of transcription and stability. This report shows that it is also controlled at the point of its substitution for SigA by a second transient competence-specific protein, ComW. PMID- 27353652 TI - cis-Encoded Small RNAs, a Conserved Mechanism for Repression of Polysaccharide Utilization in Bacteroides. AB - Bacteroides is a major component of the human gut microbiota which has a broad impact on the development and physiology of its host and a potential role in a wide range of disease syndromes. The predominance of this genus is due in large part to expansion of paralogous gene clusters, termed polysaccharide utilization loci (PULs), dedicated to the uptake and catabolism of host-derived and dietary polysaccharides. The nutritive value and availability of polysaccharides in the gut vary greatly; thus, their utilization is hierarchical and strictly controlled. A typical PUL includes regulatory genes that induce PUL expression in response to the presence of specific glycan substrates. However, the existence of additional regulatory mechanisms has been predicted to explain phenomena such as hierarchical control and catabolite repression. In this report, a previously unknown layer of regulatory control was discovered in Bacteroides fragilis Exploratory transcriptome sequencing (RNA-seq) analysis revealed the presence of cis-encoded antisense small RNAs (sRNAs) associated with 15 (30%) of the B. fragilis PULs. A model system using the Don (degradation of N-glycans) PUL showed that the donS sRNA negatively regulated Don expression at the transcriptional level, resulting in a decrease in N-glycan utilization. Additional studies performed with other Bacteroides species indicated that this regulatory mechanism is highly conserved and, interestingly, that the regulated PULs appear to be closely linked to the utilization of host-derived glycans rather than dietary plant polysaccharides. The findings described here demonstrate a global control mechanism underlying known PUL regulatory circuits and provide insight into regulation of Bacteroides physiology. IMPORTANCE: The human gut is colonized by a dense microbiota which is essential to the health and normal development of the host. A key to gut homeostasis is the preservation of a stable, diverse microbiota. Bacteroides is a dominant genus in the gut, and the ability of Bacteroides species to efficiently compete for a wide range of glycan energy sources is a crucial advantage for colonization. Glycan utilization is mediated by a large number of polysaccharide utilization loci (PULs) which are regulated by substrate induction. In this report, a novel family of antisense sRNAs is described whose members repress gene expression in a distinct subset of PULs. This repression downregulates PUL expression in the presence of energy sources that are more readily utilized such as glucose, thereby allowing efficient glycan utilization. PMID- 27353651 TI - Partial Diversity Generates Effector Immunity Specificity of the Bac41-Like Bacteriocins of Enterococcus faecalis Clinical Strains. AB - Bacteriocin 41 (Bac41) is the plasmid-encoded bacteriocin produced by the opportunistic pathogen Enterococcus faecalis Its genetic determinant consists of bacL1 (effector), bacL2 (regulator), bacA (effector), and bacI (immunity). The secreted effectors BacL1 and BacA coordinate to induce the lytic cell death of E. faecalis Meanwhile, the immunity factor BacI provides self-resistance to the Bac41 producer, E. faecalis, against the action of BacL1 and BacA. In this study, we demonstrated that more than half of the 327 clinical strains of E. faecalis screened had functional Bac41 genes. Analysis of the genetic structure of the Bac41 genes in the DNA sequences of the E. faecalis strains revealed that the Bac41-like genes consist of a relatively conserved region and a variable region located downstream from bacA Based on similarities in the variable region, the Bac41-like genes could be classified into type I, type IIa, and type IIb. Interestingly, the distinct Bac41 types had specific immunity factors for self resistance, BacI1 or BacI2, and did not show cross-immunity to the other type of effector. We also demonstrated experimentally that the specificity of the immunity was determined by the combination of the C-terminal region of BacA and the presence of the unique BacI1 or BacI2 factor. These observations suggested that Bac41-like bacteriocin genes are extensively disseminated among E. faecalis strains in the clinical environment and can be grouped into at least three types. It was also indicated that the partial diversity results in specificity of self resistance which may offer these strains a competitive advantage. IMPORTANCE: Bacteriocins are antibacterial effectors produced by bacteria. In general, a bacteriocin-coding gene is accompanied by a cognate immunity gene that confers self-resistance on the bacteriocin-producing bacterium itself. We demonstrated that one of the bacteriocins, Bac41, is disseminated among E. faecalis clinical strains and the Bac41 subtypes with partial diversity. The Bac41-like bacteriocins were found to be classified into type I, type IIa, and type IIb by variation of the cognate immunity factors. The antibacterial activity of the respective effectors was specifically inhibited by the immunity factor from the same type of Bac41 but not the other types. This specificity of effector-immunity pairs suggests that bacteriocin genes might have evolved to change the immunity specificity to acquire an advantage in interbacterial competition. PMID- 27353653 TI - MicroRNA-140 Inhibits Cell Proliferation in Gastric Cancer Cell Line HGC-27 by Suppressing SOX4. AB - BACKGROUND Gastric cancer is a malignant tumor with a high morbidity and mortality. MicroRNAs are important regulators of gene expression, influencing the progression of gastric cancer. This study aimed to reveal the role of microRNA 140 (miR-140) in gastric cancer cell proliferation and its potential mechanisms. MATERIAL AND METHODS Gastric cancer tissues and cell lines BGC-823, SGC-7901, and HGC-27 were used to analyze miR-140 levels compared to normal tissues and cell line GES-1. In HGC-27 cells transfected with miR-140 mimic, we performed MTT, colony formation assay, and cell cycle assay by flow cytometry. SOX4, a predicted target of miR-140, was mutated to verify its regulation by miR-140, and was overexpressed to analyze its function in cell proliferation. Doxorubicin treatment was performed to investigate the effect of miR-140 on drug resistance. RESULTS miR-140 was down-regulated in gastric cancer tissues and cell lines, with the lowest expression level in HGC-27. miR-140 overexpression inhibited HGC-27 cell viability and colony formation and resulted in G0/G1 arrest. miR-140 suppressed SOX4 expression via binding to the 3' untranslated region, while the mutant SOX4 could not be regulated. Overexpressing SOX4 led to promoted cell viability, colony formation, and cell cycle progress. miR-140 overexpression also improved the anti-viability effects of doxorubicin, suggesting its potential in reducing the drug resistance of gastric cells. CONCLUSIONS These findings suggest that miR-140 directly inhibits SOX4, which might be one of its mechanisms in suppressing gastric cancer cell proliferation. This study provides a promising therapeutic strategy for treating gastric cancer and facilitates microRNA research in various diseases. PMID- 27353654 TI - Structured substrates and delivery vehicles: trending now in biomedicine. PMID- 27353655 TI - The use of hyperthermia in the treatment of bladder cancer. PMID- 27353656 TI - Lupus anticoagulants associated inhibitor against factor IX in a young patient with haemophilia B. PMID- 27353657 TI - Protein kinase A inhibition of macrophage maturation is accompanied by an increase in DNA methylation of the colony-stimulating factor 1 receptor gene. AB - Macrophage colony-stimulating factor 1 (CSF-1) plays a critical role in the differentiation of mononuclear phagocytes from bone marrow precursors, and maturing monocytes and macrophages exhibit increased expression of the CSF-1 receptor, CSF1R. The expression of CSF1R is tightly regulated by transcription factors and epigenetic mechanisms. We previously showed that prostaglandin E2 and subsequent activation of protein kinase A (PKA) inhibited CSF1R expression and macrophage maturation. Here, we examine the DNA methylation changes that occur at the Csf1r locus during macrophage maturation in the presence or absence of activated PKA. Murine bone marrow cells were matured to macrophages by incubating cells with CSF-1-containing conditioned medium for up to 6 days in the presence or absence of the PKA agonist 6-bnz-cAMP. DNA methylation of Csf1r promoter and enhancer regions was assayed by bisulphite pyrosequencing. DNA methylation of Csf1r decreased during normal macrophage maturation in concert with an increase in Csf1r mRNA expression. Treatment with the PKA agonist inhibited Csf1r mRNA and protein expression, and increased DNA methylation at the Csf1r promoter. This was associated with decreased binding of the transcription factor PU.1 to the Csf1r promoter. Treatment with the PKA agonist inhibited the responsiveness of macrophages to CSF-1. Levels of endogenous PKA activity decreased during normal macrophage maturation, suggesting that attenuation of this signalling pathway contributes to the increase in CSF1R expression during macrophage maturation. Together, these results demonstrate that macrophage maturation is accompanied by Csf1r hypomethylation, and illustrates for the first time the ability of PKA to increase Csf1r DNA methylation. PMID- 27353658 TI - Methane and carbon dioxide flux in the profile of wood ant (Formica aquilonia) nests and the surrounding forest floor during a laboratory incubation. AB - We compared methane (CH4) and carbon dioxide (CO2) fluxes in samples collected from the aboveground parts of wood ant nests and in the organic and mineral layer of the surrounding forest floor. Gas fluxes were measured during a laboratory incubation, and microbial properties (abundance of fungi, bacteria and methanotrophic bacteria) and nutrient contents (total and available carbon and nitrogen) were also determined. Both CO2 and CH4 were produced from ant nest samples, indicating that the aboveground parts of wood ant nests act as sources of both gases; in comparison, the forest floor produced about four times less CO2 and consumed rather than produced CH4 Fluxes of CH4 and CO2 were positively correlated with contents of available carbon and nitrogen. The methanotrophic community was represented by type II methanotrophic bacteria, but their abundance did not explain CH4 flux. Fungal abundance was greater in ant nest samples than in forest floor samples, but bacterial abundance was similar in both kinds of samples, suggesting that the organic materials in the nests may have been too recalcitrant for bacteria to decompose. The results indicate that the aboveground parts of wood ant nests are hot spots of CO2 and CH4 production in the forest floor. PMID- 27353659 TI - Endophytic microbial diversity of the halophyte Arthrocnemum macrostachyum across plant compartments. AB - In this study, the microbial community structures of the endosphere of the halophyte Arthrocnemum macrostachyum were evaluated from two locations in Mallorca, Spain, focusing on three plant compartments (roots, green and red stems) compared to the rhizospheric soil where the plants grew. The physicochemical parameters of the rhizospheric soils differed between locations, and the soils were characterized by different microbial community structures. Accordingly, the endophytic community composition, mainly composed of putatively halophilic organisms, was highly influenced by the rhizospheric soil microbiota, as revealed by the co-occurrence of the major endophytic taxa in the endosphere and the rizospheric soils. Moreover, the reduction of diversity from the endorhizosphere towards the red leaves may support the fact that part of colonization of the plant by bacteria could have an origin in the rhizospheric soils through the roots and subsequent migration to the aerial parts of the plant. Finally, there were certain relevant ubiquitous taxa, such as Chromohalobacter canadensis, Rudaea cellulosilytica (never reported before as endophytic), Psychrobacter sp., Bradyrhizobium sp. and Halomonas sp., that, due their moderate halophilic nature, seemed to find an optimal environment inside the plants. Some of these relevant endophytes were not always detectable in their respective soils, and were probably part of the soils' rare biosphere, which would gain preponderance in a favorable endophytic environment. PMID- 27353660 TI - Spatial and taxonomical overlap of fungi on phylloplanes and invasive alien ladybirds with fungal infections in tree crowns of urban green spaces. AB - Occurrence of entomopathogenic fungi on phylloplanes in Tilia * europaea crowns between 1 and 13 m was assessed in urban parks. Prevalence of fungal infections in ladybirds (Coleoptera: Coccinellidae) collected from Tilia * europaea was assessed to determine whether fungi found on phylloplanes also occurred as infections in ladybirds. Isaria spp. was most abundant on phylloplanes (mean colony forming units (CFU) per leaf +/- SE, 0.33 +/- 0.03) followed by Beauveria spp. (0.22 +/- 0.02 CFU per leaf) and Lecanicillium spp. (0.19 +/- 0.02 CFU per leaf). Densities of inoculum were higher in inner crowns and decreased with height, although Lecanicillium spp. peaked at 5-7 m. Upper phylloplane surfaces harboured higher densities of Isaria spp. and Beauveria spp. than lower surfaces, whereas Lecanicillium spp. was equally distributed. Most prevalent on ladybirds were Isaria spp. (20.6% Harmonia axyridis; 4.8% natives), Lecanicillium spp. (13.6% H. axyridis; 4.8% natives), with fewer Beauveria spp. infections (2.6% H. axyridis). Molecular identification revealed Beauveria bassiana, B. pseudobassiana, Isaria farinosa and Lecanicillium muscarium among isolates of both tree and ladybird origin. Tilia * europaea phylloplanes support a diverse assemblage of entomopathogenic fungal species with a different prevalence in coccinellids compared to their relative abundance in this habitat. PMID- 27353661 TI - Disulfiram chelated with copper promotes apoptosis in human breast cancer cells by impairing the mitochondria functions. AB - Disulfiram (DSF) has been proved to have broad-spectrum anti-alcoholism effects, and it is also found to show stronger anti-tumor effects after chelating with Cu2+ to form DSF-Cu complex. In this work, we studied the anti-tumor activity of DSF-Cu in MCF-7 cells by flow cytometry, confocal laser scanning microscope, and atomic force microscopy to clarify the underlying anti-tumor mechanisms. MCF-7 cells were incubated with 50, 100, 150, 200, and 250 nM DSF chelated with 10 uM CuCl2 for 24 h. The results showed that DSF-Cu could induce the accumulation of MCF-7 cells in G2/M phase and apoptosis in a concentration-dependent manner. Additionally, atomic force microscope (AFM) analysis at nanoscale level showed that the morphology of cell was significantly shrunk with destroyed filopodia and ultrastructure presented many irregular protuberances on the cell membrane after DSF-Cu treatment, which was closely associated with the re-arrangement of cytoskeleton. DSF-Cu induced the production of reactive oxygen species (ROS), increased the concentration of intracellular Ca2+ and decreased the mitochondrial membrane potential (MMP) in MCF-7 cells resulting in a mitochondria-dependent apoptosis pathway. The results indicated that DSF-Cu has a potential anti-tumor activity in breast cancer by impairing the mitochondria functions. SCANNING 38:825-836, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27353662 TI - Rates of Community-based Antibiotic Prescriptions and Hospital-treated Infections in Individuals With and Without Type 2 Diabetes: A Danish Nationwide Cohort Study, 2004-2012. AB - BACKGROUND: The excess risk of antibiotic use and hospital-treated infections in patients with type 2 diabetes (T2D) compared with general population is poorly understood. METHODS: In a nationwide cohort of patients with incident T2D (n = 155 158) and an age-, gender-, and residence-matched comparison cohort (n = 774 017), we used Cox regression to compute rates and confounder-adjusted rate ratios (aRRs) of community-based antibiotic prescription redemption and hospital-treated infections during 2004-2012. RESULTS: The rates of community-based antibiotic prescriptions in the T2D and comparison cohorts were 364 vs 275 per 1000 person years after a median follow-up of 1.1 years (aRR = 1.24; 95% confidence interval [CI], 1.23 to 1.25). The corresponding rates for hospital-treated infection were 58 vs 39 per 1000 person-years after a median follow-up of 2.8 years (aRR = 1.49; 95% CI, 1.47 to 1.52). The aRRs were increased particularly for urinary tract infections (UTIs, 1.41; 95% CI, 1.35 to 1.45), skin infections (1.50; 95% CI, 1.45 to 1.55), septicemia (1.60; 95% CI, 1.53 to 1.67), and tuberculosis (1.61; 95% CI, 1.25 to 2.06) and of community-based antibiotics prescribed for UTIs (1.31; 95% CI, 1.29 to 1.33), Staphylococcus aureus infections (1.32; 95% CI, 1.30 to 1.34), and mycobacterial infections (1.69; 95% CI, 1.36 to 2.09). The 1 year aRR declined from 1.89 (95% CI, 1.75 to 2.04) in 2004 to 1.59 (95% CI, 1.45 to 1.74) in 2011 for hospital-treated infection (trend P = .007) and from 1.31 (95% CI, 1.27 to 1.36) in 2004 to 1.26 (95% CI, 1.22 to 1.30) in 2011 for community-based antibiotic prescriptions (trend P = .006). CONCLUSIONS: Patients with T2D have rates of community-based antibiotic prescriptions and hospital treated infections that are higher than for the general population. PMID- 27353663 TI - Kinetic Analysis of Biomarkers in a Cohort of US Patients With Ebola Virus Disease. AB - BACKGROUND: Ebola virus (EBOV) infection causes a severe and often fatal disease. Despite the fact that more than 30 000 individuals have acquired Ebola virus disease (EVD), the medical and scientific community still does not have a clear understanding of the mechanisms by which EBOV causes such severe disease. METHODS: In this study, 54 biomarkers in plasma samples serially collected from 7 patients with EVD were analyzed in an attempt to define the kinetics of inflammatory modulators. Two clinical disease groups were defined (moderate and severe) based on the need for clinical support. Biomarkers were evaluated for correlation with viremia and clinical disease in an effort to identify pathways that could be useful targets of therapeutic intervention. RESULTS: Patients with severe disease had higher viremia than those with moderate disease. Several biomarkers of immune activation and control were significantly elevated in patients with moderate disease. A series of pro-inflammatory cytokines and chemokines were significantly elevated in patients with severe disease. CONCLUSIONS: Biomarkers that were associated with severe EVD were proinflammatory and indicative of endothelial or coagulation cascade dysfunction, as has been seen historically in patients with fatal outcomes. In contrast, biomarkers that were associated with moderate EVD were suggestive of a strong interferon response and control of both innate and adaptive responses. Therefore, clinical interventions that modulate the phenotype and magnitude of immune activation may be beneficial in treating EVD. PMID- 27353664 TI - Editorial Commentary: Toxoplasmosis: Cats Have It, Humans Get It, but How Much Disease Does It Cause? PMID- 27353666 TI - Pride in autistic diversity. PMID- 27353665 TI - Understanding Toxoplasmosis in the United States Through "Large Data" Analyses. AB - BACKGROUND: Toxoplasma gondii infection causes substantial morbidity and mortality in the United States, and infects approximately one-third of persons globally. Clinical manifestations vary. Seropositivity is associated with neurologic diseases and malignancies. There are few objective data concerning US incidence and distribution of toxoplasmosis. METHODS: Truven Health MarketScan Database and International Classification of Diseases, Ninth Revision (ICD-9) codes, including treatment specific to toxoplasmosis, identified patients with this disease. Spatiotemporal distribution and patterns of disease manifestation were analyzed. Comorbidities between patients and matched controls were compared. RESULTS: Between 2003 and 2012, 9260 patients had ICD-9 codes for toxoplasmosis. This database of patients with ICD-9 codes includes 15% of those in the United States, excluding patients with no or public insurance. Thus, assuming that demographics do not change incidence, the calculated total is 61 700 or 6856 patients per year. Disease was more prevalent in the South. Mean age at diagnosis was 37.5 +/- 15.5 years; 2.4% were children aged 0-2 years, likely congenitally infected. Forty-one percent were male, and 73% of women were of reproductive age. Of identified patients, 38% had eye disease and 12% presented with other serious manifestations, including central nervous system and visceral organ damage. Toxoplasmosis was statistically associated with substantial comorbidities, including human immunodeficiency virus, autoimmune diseases, and neurologic diseases. CONCLUSIONS: Toxoplasmosis causes morbidity and mortality in the United States. Our analysis of private insurance records missed certain at-risk populations and revealed fewer cases of retinal disease than previously estimated, suggesting undercoding, underreporting, undertreating, or differing demographics of those with eye disease. Mandatory reporting of infection to health departments and gestational screening could improve care and facilitate detection of epidemics and, thereby, public health interventions. PMID- 27353667 TI - Sickle-cell disease: managing comorbidities. PMID- 27353668 TI - Self-medicating in the opioid crisis. PMID- 27353669 TI - AIDS 2016: from aspiration to implementation. PMID- 27353670 TI - WHO recommendations on shorter treatment of multidrug-resistant tuberculosis. PMID- 27353672 TI - US presidential candidates urged to support health research. PMID- 27353673 TI - Yellow fever continues to spread in Angola. PMID- 27353674 TI - Canada's Indigenous suicide crisis. PMID- 27353675 TI - The Lancet Technology: pharming blood. PMID- 27353676 TI - Invasive strategy in acute coronary syndrome. PMID- 27353677 TI - Invasive strategy in acute coronary syndrome. PMID- 27353678 TI - Invasive strategy in acute coronary syndrome. PMID- 27353679 TI - The double burden of malnutrition associated with poverty. PMID- 27353680 TI - Invasive strategy in acute coronary syndrome - Authors' reply. PMID- 27353681 TI - Treatment false advertisement in China: a tragedy. PMID- 27353682 TI - Regulating illegal drug markets: what legal markets can teach us. PMID- 27353683 TI - Out-of-pocket payments in Nigeria. PMID- 27353684 TI - Department of Error. PMID- 27353685 TI - The intersection between asthma and acute chest syndrome in children with sickle cell anaemia. AB - Acute chest syndrome is a frequent cause of acute lung disease in children with sickle-cell disease. Asthma is common in children with sickle-cell disease and is associated with increased incidence of vaso-occlusive pain events, acute chest syndrome episodes, and earlier death. Risk factors for asthma exacerbation and an acute chest syndrome episode are similar, and both can present with shortness of breath, chest pain, cough, and wheezing. Despite overlapping risk factors and symptoms, an acute exacerbation of asthma or an episode of acute chest syndrome are two distinct entities that need disease-specific management strategies. Although understanding has increased about asthma as a comorbidity in sickle-cell disease and its effects on morbidity, substantial gaps remain in knowledge about best management. PMID- 27353686 TI - Fetal haemoglobin in sickle-cell disease: from genetic epidemiology to new therapeutic strategies. AB - Sickle-cell disease affects millions of individuals worldwide, but the global incidence is concentrated in Africa. The burden of sickle-cell disease is expected to continue to rise over the coming decades, adding to stress on the health infrastructures of many countries. Although the molecular cause of sickle cell disease has been known for more than half a century, treatment options remain greatly limited. Allogeneic haemopoietic stem-cell transplantation is the only existing cure but is limited to specialised clinical centres and remains inaccessible for most patients. Induction of fetal haemoglobin production is a promising strategy for the treatment of sickle-cell disease. In this Series paper, we review scientific breakthroughs in epidemiology, genetics, and molecular biology that have brought reactivation of fetal haemoglobin to the forefront of sickle-cell disease research. Improved knowledge of the regulation of fetal haemoglobin production in human beings and the development of genome editing technology now support the design of innovative therapies for sickle-cell disease that are based on fetal haemoglobin. PMID- 27353688 TI - Sonographic and Power Doppler Evaluation of an Invasive Mole Located in a Cesarean Scar Pregnancy. PMID- 27353687 TI - Cardiovascular complications and risk of death in sickle-cell disease. AB - In sickle-cell disease, a point mutation in the beta-globin chain causes haemoglobin to polymerise within erythrocytes during deoxygenation, altering red blood cell rheology and causing haemolysis. Improvements in health infrastructure, preventive care, and clinical treatments have reduced the morbidity and mortality of sickle-cell disease in developed countries. However, as these patients live longer, the chronic effects of sustained haemolytic anaemia and episodic vaso-occlusive events drive the development of end-organ complications. Cardiopulmonary organ dysfunction and chronic kidney injury have a large effect on morbidity and premature mortality, and typically accelerate in the second decade of life. These processes culminate in the development of pulmonary hypertension, left ventricular diastolic heart disease, dysrhythmia, and sudden death. In this Series paper, we review the mechanisms, clinical features, and epidemiology of major cardiovascular complications in patients with sickle-cell disease and discuss how screening and intervention could reduce their incidence. PMID- 27353689 TI - Early First-Trimester Appearance of a Hydatidiform Mole on Sonography: The "Snowball" Sign. PMID- 27353690 TI - Re: ACES: Accurate Cervical Evaluation With Sonography. PMID- 27353691 TI - Erratum. PMID- 27353692 TI - Correction: Site controlled red-yellow-green light emitting InGaN quantum discs on nano-tipped GaN rods. AB - Correction for 'Site controlled red-yellow-green light emitting InGaN quantum discs on nano-tipped GaN rods' by M. Conroy et al., Nanoscale, 2016, 8, 11019 11026. PMID- 27353693 TI - Hospitalized Children With Encephalitis in the United States: A Pediatric Health Information System Database Study. AB - OBJECTIVES: Given the paucity of data on resource utilization among children with encephalitis, the objective of this study was to describe the epidemiology and evaluate resource utilization and discharge data of children with encephalitis admitted to US hospitals from 2004 to 2013. METHODS: We conducted a retrospective cohort study utilizing the Pediatric Health Information System database of children aged 0 to 18 years with the International Classification of Diseases, Ninth Revision codes for encephalitis from 2004 to 2013. Only the initial admissions were included, and the age group analyzed was 0 to 18 years. RESULTS: Among 7298 children with encephalitis, 2933 (40%) were admitted to a pediatric intensive care unit. The median age was nine years, the overall median length of stay was 16 days, and children requiring critical care had a median length of stay of 25 days. Children in the pediatric intensive care unit were more likely to have seizures (P <0.001) and head magnetic resonance imaging (P <0.001) than children on the floor. Similarly, children requiring critical care were more likely to have a broad diagnostic evaluation sent including cerebrospinal fluid cultures, blood bacterial and fungal cultures, western equine encephalitis antibody, St. Louis equine encephalitis antibody, varicella-zoster serology, human immunodeficiency virus 1 antibody, human immunodeficiency virus DNA polymerase chain reaction, acid-fast stain, and Lyme disease serology. Seventeen percent of children were treated with intravenous immunoglobulin, and 4% underwent plasmapheresis. There was a trend of increasing use of intravenous immunoglobulin and plasmapheresis in children with encephalitis over the study period. A total of 5944 (81%) children were discharged home, and the mortality in this cohort was 3% (230). The mean charges for hospitalization for a child with encephalitis was $64,604 and for those requiring critical care was $260,012. CONCLUSIONS: Encephalitis is a significant cause of morbidity and mortality in children. Children with encephalitis admitted to the pediatric intensive care unit are more likely to have seizures and to undergo a more extensive evaluation to determine the cause of encephalitis. Use of plasmapheresis and intravenous immunoglobulin is on the rise in hospitalized children. Prospective studies are necessary to better understand treatment and intervention strategies for children with encephalitis and their impact on outcomes. PMID- 27353694 TI - Contribution of Histologic Chorioamnionitis and Fetal Inflammatory Response Syndrome to Increased Risk of Brain Injury in Infants With Preterm Premature Rupture of Membranes. AB - BACKGROUND: To determine the association of histologic chorioamnionitis (HCA) and fetal inflammatory response syndrome (FIRS) with brain injuries in infants born to mothers with preterm premature rupture of membranes. METHODS: A total of 103 singleton infants born to mothers with preterm premature rupture of membranes were enrolled. The placental inflammation was confirmed by HCA, and FIRS was defined in fetuses with preterm labor and an elevation of the fetal plasma interleukin-6 concentration. Examination of brain images was conducted to confirm the existence of brain injuries. Based on placental HCA and umbilical cord blood interleukin-6 level, all patients were divided into three groups: HCA(-)FIRS(+), HCA(+)FIRS(-), and HCA(+)FIRS(+). RESULTS: Among all infants with preterm premature rupture of membranes, 53.40% were exposed to HCA, 20.38% experienced FIRS, and the overall incidence of brain injuries was 38.83%. The incidence of brain injury in HCA(-)FIRS(+), HCA(+)FIRS(-), and HCA(+)FIRS(+) groups were 20.83%, 41.18%, and 76.19%, respectively. HCA at the advanced grades and stages was associated with increased risk of brain injury. Umbilical cord blood levels of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF alpha), and granulocyte-colony stimulating factor (G-CSF) in premature infants with brain injuries were significantly higher than in those without brain injuries. Infants diagnosed with both HCA and FIRS showed significantly higher levels of IL-8, TNF-alpha, and G-CSF than those with HCA alone. CONCLUSIONS: Preterm infants exposed to severe chorioamnionitis had an increased risk of brain injury. IL-6, IL-8, TNF-alpha, and G-CSF in cord blood were associated with brain injuries in preterm infants and may be used as extradiagnostic criteria. PMID- 27353695 TI - Predictors of Cognitive Functions in Children With Sturge-Weber Syndrome: A Longitudinal Study. AB - BACKGROUND: Sturge-Weber syndrome is often accompanied by seizures and neurocognitive deterioration, although previous studies have suggested that early functional brain reorganization may diminish the cognitive sequelae in some children with unilateral Sturge-Weber syndrome. The "rules" governing these plasticity mechanisms are poorly understood. In this study, we evaluated longitudinal changes of cognitive functioning (intelligence quotient [IQ]) and assessed the performance of clinical, electroencephalography (EEG), and magnetic resonance imaging (MRI) variables for predicting IQ in children with Sturge-Weber syndrome. METHODS: Thirty-three young children (mean age: 3.3 years at baseline) with unilateral Sturge-Weber syndrome underwent MRI, scalp EEG, and neuropsychology evaluation twice, with a median follow-up of 2 years. None of the children had epilepsy surgery. Longitudinal IQ changes were calculated. Seizure variables, interictal EEG abnormalities, and extent and location of MRI brain involvement were correlated with IQ assessed at follow-up. RESULTS: Global IQ showed a highly variable course with both increases and decreases over time. Lower IQ at baseline was associated with interval IQ increase. In univariate analyses, lower outcome IQ was associated with baseline EEG abnormalities (P < 0.001), young age at seizure onset (P = 0.001), high seizure frequency (P = 0.02), and early frontal-lobe involvement on MRI (P = 0.01). In multivariate analysis, EEG abnormalities at baseline remained a robust, independent predictor of outcome IQ. CONCLUSIONS: The early trajectory of cognitive changes in children with unilateral Sturge-Weber syndrome is highly variable; children with improving IQ likely undergo effective unimpeded functional reorganization. Early onset, frequent seizures, and interictal epileptiform abnormalities on EEG likely interfere with this process resulting in poor cognitive functions. Future studies assessing interventions should target this high-risk subgroup to optimize cognitive outcome in Sturge-Weber syndrome. PMID- 27353696 TI - Severe Neurological Complications Associated With Tourette Syndrome. AB - BACKGROUND: Tics and Tourette syndrome are common problems evaluated by both the general pediatrician and pediatric neurologist. The common comorbidities of tics are well known, but the severe neurological complications are rare and may not be appreciated. METHODS: This is a retrospective case series and literature review. RESULTS: We present here four adolescents with Tourette syndrome who had severe neurological complications secondary to motor tics. We provide the history, neurological examination, and radiological findings in addition to a review of previously reported cases of vascular and cervical cord complications associated with violent motor tics. CONCLUSIONS: We highlight the importance of recognizing the presenting signs of these complications early and the need to vigorously treat violent motor tics to prevent significant neurological complications. PMID- 27353697 TI - Imaging Flow Cytometry Analysis to Identify Differences of Survival Motor Neuron Protein Expression in Patients With Spinal Muscular Atrophy. AB - BACKGROUND: Spinal muscular atrophy is a neurodegenerative disorder caused by the deficient expression of survival motor neuron protein in motor neurons. A major goal of disease-modifying therapy is to increase survival motor neuron expression. Changes in survival motor neuron protein expression can be monitored via peripheral blood cells in patients; therefore we tested the sensitivity and utility of imaging flow cytometry for this purpose. METHODS: After the immortalization of peripheral blood lymphocytes from a human healthy control subject and two patients with spinal muscular atrophy type 1 with two and three copies of SMN2 gene, respectively, we used imaging flow cytometry analysis to identify significant differences in survival motor neuron expression. A bright detail intensity analysis was used to investigate differences in the cellular localization of survival motor neuron protein. RESULTS: Survival motor neuron expression was significantly decreased in cells derived from patients with spinal muscular atrophy relative to those derived from a healthy control subject. Moreover, survival motor neuron expression correlated with the clinical severity of spinal muscular atrophy according to SMN2 copy number. The cellular accumulation of survival motor neuron protein was also significantly decreased in cells derived from patients with spinal muscular atrophy relative to those derived from a healthy control subject. CONCLUSIONS: The benefits of imaging flow cytometry for peripheral blood analysis include its capacities for analyzing heterogeneous cell populations; visualizing cell morphology; and evaluating the accumulation, localization, and expression of a target protein. Imaging flow cytometry analysis should be implemented in future studies to optimize its application as a tool for spinal muscular atrophy clinical trials. PMID- 27353698 TI - A class of sulfonamides as carbonic anhydrase I and II inhibitors. AB - Four groups of novel sulfonamide derivatives: (i) acetoxybenzamide, (ii) triacetoxybenzamide, (iii) hydroxybenzamide and (iv) trihydroxybenzamide, all having thiazole, pyrimidine, pyridine, isoxazole and thiadiazole moieties were prepared and their inhibitory effects were studied on two metalloenzymes, i.e. carbonic anhydrase isozymes (hCA I and II), purified from human erythrocyte cells by Sepharose-4B-l-tyrosine-sulfanilamide affinity chromatography. These enzymes are present in almost all living organisms to catalyse the synthesis of bicarbonate ion (HCO3-) from carbon dioxide and water. The sulfonamide derivatives were found to be active against hCA I and II in the range of 2.62 136.54 and 5.74-210.58 nM, respectively. PMID- 27353699 TI - [Family medicine teaching units, trapped in the net... of bureaucracy]. PMID- 27353700 TI - [Description of clinical pathological concordance and patient satisfaction in minor surgery in a Primary Care centre]. AB - AIM: To describe the minor surgery (MS) characteristics in a Primary Care (PC) centre, and to evaluate the clinical pathological concordance and patient satisfaction. DESIGN: Descriptive and retrospective study. SETTING: Primary Care, urban health care centre, Almeria, Spain. PARTICIPANTS: The population were the patients belonging to urban Primary Health Care centre, referred by their family physicians or paediatricians for the performing of MS during year 2013, and who consented to the intervention. A sample of 223 patients was obtained. MAIN MEASUREMENTS: Variables analysed were: sex, age, locations of the lesions, type of intervention, clinical diagnosis, histopathology diagnosis, complications, and patient satisfaction. The data were extracted from the medical history, the histopathology reports, and by using a satisfaction questionnaire completed by post or telephone by the patients. RESULTS: The population consisted of 53.8% males, and had a mean age of 51.12 years (SD 19.02). The location of the most intervened lesions was in the head (35.4%). Electro-surgery was the most used procedure (62.8%), with only 16.9% of the lesions being biopsied, of which the most frequent was fibroids (32.3%). The clinical pathological concordance was >80% and the Kappa index was 0.783 (P<.001). The complications presented were low. The patient's satisfaction was high. CONCLUSIONS: Although a simple MS technique like electro-surgery has become more extensive, MS in PC remains safe and satisfactory for the user. PMID- 27353701 TI - Identification and expression profiles of neuropeptides and their G protein coupled receptors in the rice stem borer Chilo suppressalis. AB - In insects, neuropeptides play important roles in the regulation of multiple physiological processes by binding to their corresponding receptors, which are primarily G protein-coupled receptors (GPCRs). The genes encoding neuropeptides and their associated GPCRs in the rice stem borer Chilo suppressalis were identified by a transcriptomic analysis and were used to identify potential targets for the disruption of physiological processes and the protection of crops. Forty-three candidate genes were found to encode the neuropeptide precursors for all known insect neuropeptides except for arginine-vasopressin like peptide (AVLP), CNMamide, neuropeptide-like precursors 2-4 (NPLP2-4), and proctolin. In addition, novel alternative splicing variants of three neuropeptide genes (allatostatin CC, CCHamide 1, and short neuropeptide F) are reported for the first time, and 51 putative neuropeptide GPCRs were identified. Phylogenetic analyses demonstrated that 44 of these GPCRs belong to the A-family (or rhodopsin like), 5 belong to the B-family (or secretin-like), and 2 are leucine-rich repeat containing GPCRs. These GPCRs and their likely ligands were also described. qRT PCR analyses revealed the expression profiles of the neuropeptide precursors and GPCR genes in various tissues of C. suppressalis. Our study provides fundamental information that may further our understanding of neuropeptidergic signaling systems in Lepidoptera and aid in the design of peptidomimetics, pseudopeptides or small molecules capable of disrupting the physiological processes regulated by these signaling molecules and their receptors. PMID- 27353704 TI - Metal complexes as "protein surface mimetics". AB - A key challenge in chemical biology is to identify small molecule regulators for every single protein. However, protein surfaces are notoriously difficult to recognise with synthetic molecules, often having large flat surfaces that are poorly matched to traditional small molecules. In the surface mimetic approach, a supramolecular scaffold is used to project recognition groups in such a manner as to make multivalent non-covalent contacts over a large area of protein surface. Metal based supramolecular scaffolds offer unique advantages over conventional organic molecules for protein binding, including greater stereochemical and geometrical diversity conferred through the metal centre and the potential for direct assessment of binding properties and even visualisation in cells without recourse to further functionalisation. This feature article will highlight the current state of the art in protein surface recognition using metal complexes as surface mimetics. PMID- 27353703 TI - Protein-directed synthesis of highly monodispersed, spherical gold nanoparticles and their applications in multidimensional sensing. AB - An in-situ reduction method has been reported to prepare gold nanoparticles (GNPs) of 40-110 nm by using the green reducing agents of proteins, which are activated by H2O2 and the superoxide anion (). The protein of collagen turns HAuCl4 to the aqueous Au(I) ainions, which are further reduced by other proteins to be highly monodispersed and spherical GNPs of different sizes. The GNPs reduced by different proteins are found to be with the exposed {100} facets, the distinctive UV-vis absorption spectra and various colors (See Fig. 1). By means of extracting the color responses, such as red, green and blue (RGB) alterations, an in-situ reduction method-based multidimensional sensing platform is fabricated in the process of GNPs synthesis. Without further modification of GNPs, nine common proteins are found to be well detected and discriminated at different concentrations. Moreover, this sensing platform also demonstrates great potentials in qualitative and semiquantitative analysis on the individuals of these proteins with high sensitivity. Furthermore, the validation of this multidimensional sensing platform has been carried out by analysis on the spiked proteins in human urine and the target proteins in complex matrix (e.g. lysozyme in human tear). PMID- 27353702 TI - The roles of vascular endothelial growth factor in bone repair and regeneration. AB - Vascular endothelial growth factor-A (VEGF) is one of the most important growth factors for regulation of vascular development and angiogenesis. Since bone is a highly vascularized organ and angiogenesis plays an important role in osteogenesis, VEGF also influences skeletal development and postnatal bone repair. Compromised bone repair and regeneration in many patients can be attributed to impaired blood supply; thus, modulation of VEGF levels in bones represents a potential strategy for treating compromised bone repair and improving bone regeneration. This review (i) summarizes the roles of VEGF at different stages of bone repair, including the phases of inflammation, endochondral ossification, intramembranous ossification during callus formation and bone remodeling; (ii) discusses different mechanisms underlying the effects of VEGF on osteoblast function, including paracrine, autocrine and intracrine signaling during bone repair; (iii) summarizes the role of VEGF in the bone regenerative procedure, distraction osteogenesis; and (iv) reviews evidence for the effects of VEGF in the context of repair and regeneration techniques involving the use of scaffolds, skeletal stem cells and growth factors. PMID- 27353705 TI - Development of a Novel PmpD-N ELISA for Chlamydia psittaci Infection. AB - OBJECTIVE: Chlamydia psittaci is an avian respiratory pathogen and zoonotic agent. The wide prevalence of C. psittaci poses a threat to the poultry industry and its employees. However, few commercial kits are available for detecting avian antibodies excluding the in-house ELISA kit. In this study, we developed a novel ELISA kit for detecting antibodies against C. psittaci based on the N-terminal fragment of polymorphic outer membrane protein D (PmpD-N) as the coating antigen. METHODS: The antigen concentrations, primary antibody, and cut-off value were determined and optimized. The ELISA, designated PmpD-N ELISA, was assessed for sensitivity, specificity, and concordance using sera samples from 48 experimentally infected and 168 uninfected SPF chickens. RESULTS: The sensitivity and specificity of PmpD-N ELISA were 97.9%, 100%, respectively, while the concordance was 98.1% as compared to that of MOMP-ELISA. No cross-reaction with positive sera for other avian pathogens was found. Using PmpD-N ELISA, 799/836 clinical samples were positive, including 93.0% and 98.1% positivity in layers and broilers, respectively. CONCLUSION: These data indicate that indirect ELISA with PmpD-N as the antigen candidate is a promising approach for the surveillance of C. psittaci infection. PMID- 27353706 TI - Evaluation of Six Recombinant Proteins for Serological Diagnosis of Lyme Borreliosis in China. AB - OBJECTIVE: In this study, we evaluated the diagnostic efficiency of six recombinant proteins for the serodiagnosis of Lyme borreliosis (LB) and screened out the appropriate antigens to support the production of a Chinese clinical ELISA (enzyme-linked immunosorbent assay) kit for LB. METHODS: Six recombinant antigens, Fla B.g, OspC B.a, OspC B.g, P39 B.g, P83 B.g, and VlsE B.a, were used for ELISA to detect serum antibodies in LB, syphilis, and healthy controls. The ELISA results were used to generate receiver operating characteristic (ROC) curves, and the sensitivity and specificity of each protein was evaluated. All recombinant proteins were evaluated and screened by using logistic regression models. RESULTS: Two IgG (VlsE and OspC B.g) and two IgM (OspC B.g and OspC B.a) antigens were left by the logistic regression model screened. VlsE had the highest specificity for syphilis samples in the IgG test (87.7%, P<0.05). OspC B.g had the highest diagnostic value in the IgM test (AUC=0.871). Interactive effects between OspC B.a and Fla B.g could reduce the specificity of the ELISA. CONCLUSION: Three recombinant antigens, OspC B.g, OspC B.a, and VlsE B.a, were useful for ELISAs of LB. Additionally, the interaction between OspC B.a and Fla B.g should be examined in future research. PMID- 27353707 TI - Viral Etiology Relationship between Human Papillomavirus and Human Breast Cancer and Target of Gene Therapy. AB - OBJECTIVE: To explore the viral etiology of human breast cancer to determine whether there are novel molecular targets for gene therapy of breast cancer and provide evidence for the research of gene therapy and vaccine development for breast cancer. METHODS: PCR was used to screen HPV16 and HPV18 oncogenes E6 and E7 in the SKBR3 cell line and in 76 paraffin embedded breast cancer tissue samples. RNA interference was used to knock down the expression of HPV18 E6 and E7 in SKBR3 cells, then the changes in the expression of cell-cycle related proteins, cell viability, colony formation, metastasis, and cell cycle progression were determined. RESULTS: HPV18 oncogenes E6 and E7 were amplified and sequenced from the SKBR3 cells. Of the patient samples, 6.58% and 23.68% were tested to be positive for HPV18 E6 and HPV18 E7. In the cell culture models, the knockdown of HPV18 E6 and E7 inhibited the proliferation, metastasis, and cell cycle progression of SKBR3 cell. The knockdown also clearly affected the expression levels of cell cycle related proteins. CONCLUSION: HPV was a contributor to virus caused human breast cancer, suggesting that the oncogenes in HPV were potential targets for gene therapy of breast cancer. PMID- 27353708 TI - Whole Genome Sequencing and Comparisons of Different Chinese Rabies Virus Lineages Including the First Complete Genome of an Arctic-like Strain in China. AB - OBJECTIVE: To learn the rabies genome molecular characteristics and compare the difference of China rabies lineages. METHODS: The complete genomes of 12 strains from different China rabies lineages were amplified and sequenced, and all the China street strain genomes (total 43), Arctic and Arctic-like genomes were aligned using ClustalX2, the genome homologies were analyzed using MegAlign software, and the phylogenetic trees were constructed by MEGA 5. RESULTS: First Arctic-like rabies genome in China (CQH1202D) was reported, and we supplemented the rabies genome data of China, ensuring at least one genome was available in each China lineage. The genome size of China V (11908nt) is obviously shorter than other lineages' (11923-11925nt) for the difference of N-P non-coding regions. Among different lineages, the genome homologies are almost under 90%. CQH1202D (China IV lineage) has close relationship with strains from South Korea and they share about 95% genome similarities. CONCLUSION: The molecular characteristics of 6 different China rabies lineages were compared and analyzed from genome level, which benefits for continued comprehensive rabies surveillance, rabies prevention and control in China. PMID- 27353709 TI - The Status and Associated Factors of Successful Aging among Older Adults Residing in Longevity Areas in China. AB - OBJECTIVE: This study aims to assess the status of successful aging (SA) in longevity areas in China and explore multiple factors associated with SA among the young-old and oldest-old. METHODS: A total of 2296 elderly people aged 65 and older were interviewed in the longevity areas sub-sample of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2012. Baseline assessments included a researcher-administered questionnaire, physical examination, and laboratory testing. A logistic regression model was used to identify factors associated with SA. RESULTS: The prevalence of SA was 38.81% in the CLHLS in 2012. There were significant differences between ages groups, with SA compromising 56.85% among ?65 years group and 20.31% among ?100 years group (chi2trend=126.73, P<0.01). The prevalence of SA among females was 33.59%, which was significantly lower than that among males (45.58%) (chi2gender=33.65, P<0.05). In the regression analysis, having anemia (OR=0.744, 95% CI: 0.609 0.910), poor lifestyle (OR=0.697, 95% CI: 0.568-0.854), poor sleep quality (OR=0.558, 95% CI: 0.456-0.682), and central obesity (OR=0.684, 95% CI: 0.556 0.841) were the main factors associated with SA. The promoting SA rate decreased as age increased, and the group of 65-79 years had higher odds than the other age group. CONCLUSION: Preventing central obesity, improving sleep quality and promoting healthy lifestyle may contribute to achieve SA among the elderly. PMID- 27353710 TI - Cognitive Training in Older Adults with Mild Cognitive Impairment. AB - OBJECTIVE: We investigated the feasibility and efficacy of cognitive training for older adults in rural settings and with low education levels, who have mild cognitive impairment (MCI). METHODS: Forty-five older adults (ages >65 years) with MCI were assigned to treatment or control groups, at a 2:1 ratio. Cognitive training occurred in the treatment group for 2 months. The cognitive abilities of the participants were assessed at pre-training, metaphase, and post-training time points, using the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Loewenstein Occupational Therapy Cognitive Assessment (LOTCA), and Hamilton Depression Scale (HAM-D). RESULTS: Following training, cognitive abilities improved in the treatment group, based on the total scores of all 4 measures, as well as specifically on the MoCA and LOTCA. There were differences in the main effects of group and time point on some subscales, but these differences had little, if any, effect on the overall analyses. CONCLUSION: The present study demonstrated that cognitive training has beneficial effects on attention, language, orientation, visual perception, organization of visual movement, and logical questioning in patients with MCI. Furthermore, the observed effects are long-term changes. PMID- 27353711 TI - Dietary Exposure to Benzyl Butyl Phthalate in China. AB - OBJECTIVE: Benzyl butyl phthalate (BBP) is a plasticizer used in food contact materials. Dietary exposure to BBP might lead to reproduction and developmental damages to human. The present paper was aimed to assess the health risk of BBP dietary exposure in Chinese population. METHODS: The BBP contents were detected in 7409 food samples from 25 food categories by gas chromatography-mass spectrometry operated in selected ion monitoring (SIM) mode. The dietary exposures of BBP in different age and sex groups were estimated by combining the content data with food consumption data derived from 2002 China National Nutrient and Health Survey, and evaluated according to the tolerable daily intake (TDI) of BBP established by European Food safety Agency. RESULTS: It was found that BBP was undetectable in most samples and the highest level was 1.69 mg/kg detected in a vegetable oil sample. The average dietary exposure of BBP in people aged ?2 years was 1.03 MUg/kg bw per day and the highest average exposure was found in 2 6 years old children (1.98 MUg/kg bw per day). The BBP exposure in 7-12 months old children excessed 10% of tolerable daily intake (TDI) in worst scenario. . CONCLUSION: The health risk of BBP dietary exposure in Chinese population is low and, considering BBP alone, there is no safety concern. PMID- 27353712 TI - Rapid and Sensitive Chemiluminescent Enzyme Immunoassay for the Determination of Neomycin Residues in Milk. AB - Immunoassays greatly contribute to veterinary drug residue analysis. However, there are few reports on detecting neomycin residues by immunoassay. Here, a rapid and sensitive chemiluminescent enzyme immunoassay (CLIEA) was successfully developed for neomycin residue analysis. CLIEA demonstrated good cross-reactivity for neomycin, and the IC50 value was 2.4 ng/mL in buffer. The average recovery range was 88.5%-105.4% for spiked samples (10, 50, and 100 MUg/kg), and the coefficient of variation was in the range of 7.5%-14.5%. The limit of detection of CLEIA was 9.4 MUg/kg, and this method was compared with the liquid chromatography-tandem mass spectrometry method using naturally contaminated samples, producing a correlation coefficient of >0.95. We demonstrate a reliable CLIEA for the rapid screening of neomycin in milk. PMID- 27353713 TI - Occupational Exposure to Indium of Indium Smelter Workers. AB - Case reports of indium-related lung disease in workers have raised public concern to the human toxicity of indium (In) and its compounds. However, studies evaluating the exposure or health of workers in In smelting plants are rare. Therefore, in this study, we focused on four In smelting plants, with the main objective of characterizing In in smelter plants in China and discussing the potential exposure biomarkers of In exposure. We recruited 494 subjectsat four In smelting plants in China. Personal air samples, first morning urine and spot blood samples were collected. In concentrations in samples were analyzed using inductively coupled plasma mass spectrometry. In concentrations in air samples did not exceed the permissible concentration-time weighed average, but the smelter workers had a higher internal exposure to In. Positive correlations were observed between the air In and urine In concentrations, and between the air In and blood In concentrations. This study provides basic data for the following In exposure and health risk assessment. PMID- 27353714 TI - Circulating MicroRNA-21 is Downregulated in Patients with Metabolic Syndrome. AB - The microRNA-21 (miR-21) is known to play a major role in cancer progression; however, its function in the cardiovascular system appears to be even more complex and conflicting. To characterize miR-21 expression in the plasma of individuals with or without metabolic syndrome (MetS), 58 MetS cases and 96 non MetS controls were investigated. Expression levels of miR-21 were significantly decreased in the circulation of MetS subjects (OR=0.52, 95% CI: 0.29-0.92) compared with that of non-MetS subjects. Body mass index (BMI) and the number of MetS components had a negative correlation with the level of miR-21, whereas age was inversely related to the level of miR-21. No significant difference was detected in miR-21 levels between the sexes (P=0.056). MiR-21 might be a negative regulating factor in MetS. PMID- 27353715 TI - Does cardiotocography have a role in the antenatal management of pregnancy complicated by gestational diabetes mellitus? AB - BACKGROUND: Controversy surrounds the role of fetal cardiotocography (CTG) in the antenatal management of pregnancy complicated with gestational diabetes mellitus (GDM). AIM: The aim was to investigate whether antenatal CTG aids management in pregnancy complicated by GDM. MATERIALS AND METHODS: A prospective audit of 1404 consecutive antenatal CTG in women diagnosed with GDM. Outcomes for all CTG were audited to determine whether CTG altered pregnancy management. RESULTS: In women requiring combination therapy (diet and medication), 43 CTG were required to change management of a pregnancy. In women managed by diet alone with a secondary pregnancy complication, 161 CTG were required to change management. In women managed by diet alone with no secondary pregnancy complication, CTG did not change management. CONCLUSIONS: Antenatal CTG is not recommended in women with GDM managed by diet alone with no secondary pregnancy complication. Antenatal CTG is recommended in women with GDM who require combination therapy (diet and medication). The role of CTG in women managed by diet alone with a secondary pregnancy complication should be based upon the nature of the complication. PMID- 27353716 TI - Spray layer-by-layer films for photodynamic inactivation. AB - BACKGROUND: A novel approach for photodynamic inactivation of Candida albicans is proposed. This method consists of realizing inactivation using ultraviolet light (254nm) combined with spraying layer-by-layer films of acridine orange. METHODS: To evaluate the effectiveness of the approach, the C. albicans were immobilized on quartz slices and covered with the spray layer-by-layer films. The fungi were analyzed using experiments to determine cell viability, as well as by fluorescence and atomic force microscopy. RESULTS: Viability analysis of C. albicans after photodynamic inactivation assisted by the films indicates cell death. The extent of cell death increases as the number of film layers increases. Fluorescence and atomic force microscopy analyses corroborated the cell death of C. albicans, which is posited to be due to damages to the fungi cell wall. CONCLUSIONS: Our approach has the potential to be used as an alternative for photodynamic inactivation of C. albicans. In addition, this method could be used in clinical procedures, such as for the decontamination of medical devices. PMID- 27353717 TI - Bi-directional interplay between proximal and distal inputs to CA2 pyramidal neurons. AB - Hippocampal area CA2 is emerging as a critical region for memory formation. Excitatory Scaffer collateral (SC) inputs from CA3 do not express activity dependent plasticity at SC-CA2 synapses, and are governed by a large feed-forward inhibition that prevents them from engaging CA2 pyramidal neurons. However, long term depression at inhibitory synapses evoked by stimulation of SC inputs highly increases the excitatory/inhibitory balance coming from CA3 and allows the recruitment of CA2 pyramidal neurons. In contrast, distal excitatory inputs in stratum lacunosum moleculare (SLM) can drive action potential firing in CA2 pyramidal neurons and also express a long-term potentiation. However, it is unknown whether stimulation of distal inputs can also evoke plasticity at inhibitory synapses and if so, whether this plasticity can control the strength of excitatory inputs. Here we show that stimulation in SLM evokes a long-term depression at inhibitory synapses. This plasticity strongly increases the excitatory drive of both proximal and distal inputs and allows CA3 to recruit CA2 pyramidal neurons. These data reveal a bi-directional interplay between proximal and distal inputs to CA2 pyramidal neurons that is likely to play an important role in information transfer through the hippocampus. PMID- 27353718 TI - The effect of AMPA receptor blockade on spatial information acquisition, consolidation and expression in juvenile rats. AB - Improvement on spatial tasks in rats is observed during a late, postnatal developmental period (post-natal day (PND) 18 - PND 20). The developmental emergence of this spatial function occurs in conjunction with hippocampal connectivity changes and enhanced hippocampal-AMPA receptor-mediated synaptic responses. The current work investigated the effect of AMPAr blockade on the emergence and long-term storage of spatial information in juvenile rats and associated neural activity patterns in the dorsal hippocampus CA1 region. Male, Long Evans rats between the ages of PND 18 and PND 20 were systemically (i.p.) administered the AMPAr antagonist, NBQX, (0, 5 or 10mg/kg) every day prior to hidden platform water maze training (PND 18, 19 and 20), every day immediately post-training or immediately before the probe test (PND 41). NBQX administration prior to training prolonged latencies, pathlength and increased thigmotaxis during the acquisition phase. Administration of NBQX immediately posttraining had no effect on the day-to-day performance. When given a probe test 3weeks later, the saline group across all conditions spent more time in the target quadrant. Rats treated with pretraining 5mg NBQX dose showed a preference for the target quadrant while the posttraining and pretesting 5mg NBQX doses impaired the target quadrant preference. Groups injected with 10mg of NBQX pretraining, posttraining or pretesting did not show a preference for the target quadrant. c-Fos labeling in the CA1 reflected these differences in probe performance in that groups showing greater than chance dwell time in the target quadrant showed more c-Fos labeling in the CA1 region than groups that did not show a target quadrant preference. These findings provide support for the critical role of AMPA receptor mediated function in the organization and long-term storage of spatial memories acquired during the juvenile period. PMID- 27353719 TI - Effects of Sling Exercise on Flexibility, Balance Ability, Body Form, and Pain in Patients With Chronic Low Back Pain. AB - PURPOSE: The aim of this study was to investigate the effects of sling exercise on pain, balance, flexibility, and body form in patients with chronic low back pain (LBP). DESIGN: The pretest-posttest control group design. METHODS: Thirty participants with chronic lumbar pain were divided into three groups (Sling only, Sling + Swing stick flexible bar, and Sling + Ball cushion) and exercised for 12 weeks. FINDINGS: All types of sling exercises provided significant positive effects on pain scale, body balance, flexibility, and body form. In particular, the sling exercise with swing stick flexible bar or ball cushion was more effective on body form, flexibility, and balance than a sling alone. CONCLUSIONS: In conclusion, sling exercises over a period of 12 weeks had positive effects on flexibility, balance, pain, and body form in patients with chronic lumbar pain. CLINICAL RELEVANCE: This study has generated effects of sling exercise, which will assist nursing practitioners in prescribing the beneficial physical rehabilitation for patients with chronic LBP. PMID- 27353720 TI - The brainstem in late preterm birth: Born small-for-gestational-age is the "tip of the iceberg". PMID- 27353721 TI - Th17/Treg Imbalance Induced by Dietary Salt Variation Indicates Inflammation of Target Organs in Humans. AB - The functions of T helper 17 (Th17) and regulatory T (Treg) cells are tightly orchestrated through independent differentiation pathways that are involved in the secretion of pro- and anti-inflammatory cytokines induced by high-salt dietary. However, the role of imbalanced Th17/Treg ratio implicated in inflammation and target organ damage remains elusive. Here, by flow cytometry analysis, we demonstrated that switching to a high-salt diet resulted in decreased Th17 cells and reciprocally increased Treg cells, leading to a decreased Th17/Treg ratio. Meanwhile, Th17-related pathway was down-regulated after one day of high salt loading, with the increase in high salt loading as shown by microarray and RT-PCR. Subsequently, blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) observed hypoxia in the renal medulla (increased R2(*) signal) during high-salt loading, which was regressed to its baseline level in a step-down fashion during low-salt feeding. The flow-mediated vasodilatation (FMD) of the branchial artery was significantly higher on the first day of high salt loading. Collectively, these observations indicate that a short-term increase in dietary salt intake could induce reciprocal switches in Th17/Treg ratio and related cytokines, which might be the underlying cellular mechanism of high-salt dietary induced end organ inflammation and potential atherosclerotic risk. PMID- 27353722 TI - A multiple hold-out framework for Sparse Partial Least Squares. AB - BACKGROUND: Supervised classification machine learning algorithms may have limitations when studying brain diseases with heterogeneous populations, as the labels might be unreliable. More exploratory approaches, such as Sparse Partial Least Squares (SPLS), may provide insights into the brain's mechanisms by finding relationships between neuroimaging and clinical/demographic data. The identification of these relationships has the potential to improve the current understanding of disease mechanisms, refine clinical assessment tools, and stratify patients. SPLS finds multivariate associative effects in the data by computing pairs of sparse weight vectors, where each pair is used to remove its corresponding associative effect from the data by matrix deflation, before computing additional pairs. NEW METHOD: We propose a novel SPLS framework which selects the adequate number of voxels and clinical variables to describe each associative effect, and tests their reliability by fitting the model to different splits of the data. As a proof of concept, the approach was applied to find associations between grey matter probability maps and individual items of the Mini-Mental State Examination (MMSE) in a clinical sample with various degrees of dementia. RESULTS: The framework found two statistically significant associative effects between subsets of brain voxels and subsets of the questions/tasks. COMPARISON WITH EXISTING METHODS: SPLS was compared with its non-sparse version (PLS). The use of projection deflation versus a classical PLS deflation was also tested in both PLS and SPLS. CONCLUSIONS: SPLS outperformed PLS, finding statistically significant effects and providing higher correlation values in hold out data. Moreover, projection deflation provided better results. PMID- 27353724 TI - Rhinovirus species and clinical features in children hospitalised with pneumonia from Mozambique. AB - OBJECTIVES: To describe the prevalence of human rhinovirus (RV) species in children hospitalised with pneumonia in Manhica, Mozambique, and the associations between RV species and demographic, clinical and laboratory features. METHODS: Nasopharyngeal aspirates were collected from children 0 to 10 years of age (n = 277) presenting to Manhica District Hospital with clinical pneumonia. Blood samples were collected for HIV and malaria testing, blood culture and full blood counts, and a chest X-ray was performed. A panel of common respiratory viruses was investigated using two independent multiplex RT-PCR assays with primers specific for each virus and viral type. RV species and genotypes were identified by seminested PCR assays, sequencing and phylogenetic tree analyses. RESULTS: At least one respiratory virus was identified in 206 (74.4%) children hospitalised with clinical pneumonia. RV was the most common virus identified in both HIV infected (17 of 38, 44.7%) and HIV-uninfected (74 of 237, 31.2%; P = 0.100) children. RV-A was the most common RV species identified (47 of 275, 17.0%), followed by RV-C (35/275, 12.6%) and RV-B (8/275, 2.9%). Clinical presentation of the different RV species was similar and overlapping, with no particular species being associated with specific clinical features. CONCLUSIONS: RV-A and RV-C were the most common respiratory viruses identified in children hospitalised with clinical pneumonia in Manhica. Clinical presentation of RV-A and RV-C was similar and overlapping. PMID- 27353723 TI - Historical and contemporary factors generate unique butterfly communities on islands. AB - The mechanisms shaping island biotas are not yet well understood mostly because of a lack of studies comparing eco-evolutionary fingerprints over entire taxonomic groups. Here, we linked community structure (richness, frequency and nestedness) and genetic differentiation (based on mitochondrial DNA) in order to compare insular butterfly communities occurring over a key intercontinental area in the Mediterranean (Italy-Sicily-Maghreb). We found that community characteristics and genetic structure were influenced by a combination of contemporary and historical factors, and among the latter, connection during the Pleistocene had an important impact. We showed that species can be divided into two groups with radically different properties: widespread taxa had high dispersal capacity, a nested pattern of occurrence, and displayed little genetic structure, while rare species were mainly characterized by low dispersal, high turnover and genetically differentiated populations. These results offer an unprecedented view of the distinctive butterfly communities and of the main processes determining them on each studied island and highlight the importance of assessing the phylogeographic value of populations for conservation. PMID- 27353725 TI - Surface engineering of hierarchical platinum-cobalt nanowires for efficient electrocatalysis. AB - Despite intense research in past decades, the lack of high-performance catalysts for fuel cell reactions remains a challenge in realizing fuel cell technologies for transportation applications. Here we report a facile strategy for synthesizing hierarchical platinum-cobalt nanowires with high-index, platinum rich facets and ordered intermetallic structure. These structural features enable unprecedented performance for the oxygen reduction and alcohol oxidation reactions. The specific/mass activities of the platinum-cobalt nanowires for oxygen reduction reaction are 39.6/33.7 times higher than commercial Pt/C catalyst, respectively. Density functional theory simulations reveal that the active threefold hollow sites on the platinum-rich high-index facets provide an additional factor in enhancing oxygen reduction reaction activities. The nanowires are stable in the electrochemical conditions and also thermally stable. This work may represent a key step towards scalable production of high performance platinum-based nanowires for applications in catalysis and energy conversion. PMID- 27353726 TI - Identification and characterization of CD4+ T cell epitopes present in Trichinella spiralis paramyosin. AB - Trichinellosis is a worldwide zoonosis and vaccinating swine with a potent vaccine is a practical approach to prevent Trichinella infections in China. Paramyosin of T. spiralis (Ts-Pmy) was shown in our previous work to be a good vaccine candidate against Trichinella infections. Because CD4+ T cells play a crucial role in effective immunity against T. spiralis infection, identifying CD4+ T cell epitopes of paramyosin is crucial for constructing a chimeric subunit epitope vaccine. Twelve CD4+ T cell epitopes of Ts-Pmy with the highest scores were predicted and synthesized as peptides. Five of the twelve peptides, P2, P3, P4, P5 and P12, induced strong splenocyte proliferation and secretion of the Th2 cytokines IL-4 and IL-5 from rTs-Pmy-immunized mouse splenocytes. To assess the immunogenicity of CD4+ T cell epitopes in vivo, splenocytes from mice immunized with individual peptides were stimulated with the corresponding peptides. P2, P3, P4 and P5 induced strong cell proliferation and secretion of both Th1 (INF-gamma, IL-2) and Th2 (IL-4, IL-5) cytokines. The results indicate that the peptides P2, P3, P4 and P5 are immunodominant CD4+ T cell epitopes of Ts-Pmy. This study will facilitate the design of an effective epitope-based multivalent subunit vaccine against Trichinella infections. PMID- 27353727 TI - MALAT1 induces tongue cancer cells' EMT and inhibits apoptosis through Wnt/beta catenin signaling pathway. AB - BACKGROUND: MALAT1 is recognized as an oncogenic lncRNA in various malignancies. However, its expression and function in oral tongue squamous cell carcinoma are still unknown. This study aims to investigate the expression and function of MALAT1 in TSCC tissues and cells. MATERIALS AND METHODS: qPCR was performed to detect the expression of MALAT1. MALAT1 was suppressed and upregulated by plasmid transfection in TSCC cells, and then cell migration, invasion, EMT, and apoptosis were analyzed. RESULTS: LncRNA MALAT1 was upregulated in TSCC tissues and correlated with cervical lymph node metastasis in TSCC patients. Moreover, MALAT1 induced cell migration, invasion, EMT, and inhibited apoptosis by modulating Wnt/beta-catenin signaling pathway. Finally, inhibiting Wnt/beta-catenin signaling pathway attenuated the effect of exogenous MALAT1. CONCLUSION: In summary, upregulated MALAT1 in TSCC promoted EMT and inhibited cell apoptosis by modulating Wnt/beta-catenin signaling pathway. PMID- 27353729 TI - On the relationship of inter-particle cohesiveness and bulk powder behavior: Flowability of pharmaceutical powders. AB - This study investigates the relationship between particle interactions dominated by the cohesive van der Waals force and powder flowability for materials commonly used by the pharmaceutical industry in oral solid dosage formulation. This study first sought to correlate the granular Bond number, defined as the ratio of the inter-particle cohesion force to particle weight, to the flow function coefficient, a metric commonly used to assess powder flowability. However, the granular Bond number which strictly quantifies inter-particle cohesiveness was found to correlate poorly with powder flowability due to the complexity associated with particle assemblies. To account for the multitude of interactions between particles of different sizes within a powder and to more precisely predict bulk powder behavior, a population-dependent granular Bond number was proposed. The population-dependent granular Bond number which explicitly accounts for particle size distribution and described herein as a quantification of powder cohesiveness (instead of inter-particle cohesiveness) was shown to correlate well with the flow function coefficient for a wide variety of materials including four active pharmaceutical ingredients (APIs) and fourteen common pharmaceutical excipients. Due to the success of the population-dependent granular Bond number, it was extended to predict the flowability of powder blends. This so-called population-dependent multi-component granular Bond number takes into account relevant material properties and particle interactions and was used to predict the flowability of 6-component powder blends containing acetaminophen as a model cohesive active pharmaceutical ingredient. Prediction of bulk powder behavior from individual material properties as accomplished here may be highly useful in formulation development. PMID- 27353728 TI - Health related quality of life of women at the sixth week and sixth month postpartum by mode of birth. AB - BACKGROUND: Health-related quality of life of women in the postpartum period may depend on the mode of birth. However, previous findings are contradictory. AIM: To explore health-related quality of life of women at the sixth week and sixth month postpartum by mode of birth. METHODS: We performed a longitudinal prospective study in Spain that included 546 healthy primiparae aged 18 to 45 years who gave birth to a healthy newborn. At the sixth week and sixth month postpartum, we analysed sociodemographic and clinical characteristics and compared health-related quality of life (measured using the SF-36) by mode of birth (normal vaginal, forceps, vacuum-extraction, elective caesarean section, emergency caesarean section). In addition, we analysed the change in health related quality of life between the two time points for each mode of birth. FINDINGS: We did not find differences in health-related quality of life by mode of birth at the sixth week or sixth month postpartum. At the sixth week postpartum, regardless of the mode of birth, women with postpartum urinary incontinence reported lower health-related quality of life. Between the sixth week and sixth month postpartum, health-related quality of life improved for all modes of birth. CONCLUSION: While mode of birth is not directly associated with health-related quality of life, it does have an indirect relationship in the short term. Women who reported the lowest health-related quality of life were those with postpartum urinary incontinence. Most women with postpartum urinary incontinence were in the forceps group. PMID- 27353730 TI - Formulating better medicines for children-Still too far to walk. PMID- 27353731 TI - Triboelectrification: A review of experimental and mechanistic modeling approaches with a special focus on pharmaceutical powders. AB - The continuous relative motion of particles against solid surfaces in pharmaceutical manufacturing triggers multiple physio-chemical alterations generating contact charging or triboelectrification. Charged particles in manufacturing processes can actuate multiple impediments including agglomeration, segregation during flow or adhesion to process equipment. Generation of excess charge might lead to electrostatic discharges inducing severe imperilments of fire and explosions. Despite its prevalence, the electrostatic charging process is not fully understood, owing to the diverse physical, chemical and environmental factors that can affect the phenomenon. In the course of this review, some of the basic concepts involved in charge transfer have been briefly discussed highlighting the different experimental approaches employed in measuring electrostatic charges and summarizing the constituent factors responsible. Pertinent numerical models have been further conferred to analyze the different hypotheses of particle charging. PMID- 27353732 TI - Ocean acidification affects marine chemical communication by changing structure and function of peptide signalling molecules. AB - Ocean acidification is a global challenge that faces marine organisms in the near future with a predicted rapid drop in pH of up to 0.4 units by the end of this century. Effects of the change in ocean carbon chemistry and pH on the development, growth and fitness of marine animals are well documented. Recent evidence also suggests that a range of chemically mediated behaviours and interactions in marine fish and invertebrates will be affected. Marine animals use chemical cues, for example, to detect predators, for settlement, homing and reproduction. But, while effects of high CO2 conditions on these behaviours are described across many species, little is known about the underlying mechanisms, particularly in invertebrates. Here, we investigate the direct influence of future oceanic pH conditions on the structure and function of three peptide signalling molecules with an interdisciplinary combination of methods. NMR spectroscopy and quantum chemical calculations were used to assess the direct molecular influence of pH on the peptide cues, and we tested the functionality of the cues in different pH conditions using behavioural bioassays with shore crabs (Carcinus maenas) as a model system. We found that peptide signalling cues are susceptible to protonation in future pH conditions, which will alter their overall charge. We also show that structure and electrostatic properties important for receptor binding differ significantly between the peptide forms present today and the protonated signalling peptides likely to be dominating in future oceans. The bioassays suggest an impaired functionality of the signalling peptides at low pH. Physiological changes due to high CO2 conditions were found to play a less significant role in influencing the investigated behaviour. From our results, we conclude that the change of charge, structure and consequently function of signalling molecules presents one possible mechanism to explain altered behaviour under future oceanic pH conditions. PMID- 27353733 TI - Computational imaging with a balanced detector. AB - Single-pixel cameras allow to obtain images in a wide range of challenging scenarios, including broad regions of the electromagnetic spectrum and through scattering media. However, there still exist several drawbacks that single-pixel architectures must address, such as acquisition speed and imaging in the presence of ambient light. In this work we introduce balanced detection in combination with simultaneous complementary illumination in a single-pixel camera. This approach enables to acquire information even when the power of the parasite signal is higher than the signal itself. Furthermore, this novel detection scheme increases both the frame rate and the signal-to-noise ratio of the system. By means of a fast digital micromirror device together with a low numerical aperture collecting system, we are able to produce a live-feed video with a resolution of 64 * 64 pixels at 5 Hz. With advanced undersampling techniques, such as compressive sensing, we can acquire information at rates of 25 Hz. By using this strategy, we foresee real-time biological imaging with large area detectors in conditions where array sensors are unable to operate properly, such as infrared imaging and dealing with objects embedded in turbid media. PMID- 27353734 TI - Erratum to: Safety of concurrent treatment of cats with fluralaner and emodepsid praziquantel. PMID- 27353735 TI - Functional properties of spinach (Spinacia oleracea L.) phytochemicals and bioactives. AB - Overwhelming evidence indicates that diets rich in fruits and vegetables are protective against common chronic diseases, such as cancer, obesity and cardiovascular disease. Leafy green vegetables, in particular, are recognized as having substantial health-promoting activities that are attributed to the functional properties of their nutrients and non-essential chemical compounds. Spinach (Spinacia oleracea L.) is widely regarded as a functional food due to its diverse nutritional composition, which includes vitamins and minerals, and to its phytochemicals and bioactives that promote health beyond basic nutrition. Spinach derived phytochemicals and bioactives are able to (i) scavenge reactive oxygen species and prevent macromolecular oxidative damage, (ii) modulate expression and activity of genes involved in metabolism, proliferation, inflammation, and antioxidant defence, and (iii) curb food intake by inducing secretion of satiety hormones. These biological activities contribute to the anti-cancer, anti obesity, hypoglycemic, and hypolipidemic properties of spinach. Despite these valuable attributes, spinach consumption remains low in comparison to other leafy green vegetables. This review examines the functional properties of spinach in cell culture, animals and humans with a focus on the molecular mechanisms by which spinach-derived non-essential phytochemicals and bioactives, such as glycolipids and thylakoids, impart their health benefits. PMID- 27353736 TI - Guidance is needed on synthetic cannabinoid receptor agonists and cannabis. PMID- 27353737 TI - Retraction of "Polycyclic Aromatic Hydrocarbon (PAH) and Oxygenated PAH (OPAH) Air-Water Exchange during the Deepwater Horizon Oil Spill". PMID- 27353738 TI - Clinical characteristics and predictors of gangrene in patients with systemic sclerosis and digital ulcers in the Digital Ulcer Outcome Registry: a prospective, observational cohort. PMID- 27353739 TI - A Case of Vitamin D-Dependent Rickets Type 1A with a Novel Mutation in the Uzbek Population. AB - Vitamin D-dependent rickets type 1A (VDDR-1A) (Online Mendelian Inheritance in Man #264700) is a rare, autosomal recessively inherited disorder due to inactivating mutations in CYP27B1. It is characterized by early onset of rickets with hypocalcemia. We aimed to describe the clinical and laboratory findings in a VDDR-1A case and to report a novel homozygote truncating mutation NM_000785.3 c.403C>T (p.Q135*) in CYP27B1 which to our knowledge is the first described mutation in the Uzbek population. The patient was admitted with tetany at the age of 12 months. He was a healthy Uzbek boy until 9 months of age when he had a seizure due to hypocalcemia. Vitamin D treatment was given orally in Turkmenistan (no data available for dose and duration). The patient was the product of a consanguineous marriage. His brother had died with hypocalcemia and pneumonia. At physical examination, anthropometric measurements were within normal limits; he had caput quadratum, enlarged wrists, and carpopedal spasm. Blood calcium, phosphorus, alkaline phosphatase, and parathormone (PTH) levels were 5.9 mg/dL, 3.5 mg/dL, 987 IU/L, and 182.8 pg/mL (12-72), respectively. Radiological findings included cupping and fraying of the radial and ulnar metaphyses. Renal ultrasound revealed nephrocalcinosis (grade 1). Despite high serum PTH and 25-hydroxyvitamin D3 levels, 1,25-dihydroxyvitamin D3 level was low, suggesting a diagnosis of VDDR 1A. The patient was treated with calcium carbonate and calcitriol. DNA sequencing revealed a novel homozygous mutation of NM_000785.3 c.403C>T (p.Q135*) in CYP27B1. VDDR-1A is a rare disorder which needs to be considered even in countries where nutritional vitamin D deficiency is still common. PMID- 27353741 TI - The value of liver magnetic resonance imaging in patients with findings of resectable pancreatic cancer on computed tomography. AB - INTRODUCTION: Accurate staging of patients with pancreatic cancer is important to avoid unnecessary operations. The aim of this study was to prospectively assess the impact of magnetic resonance (MR) imaging on preoperative staging of liver in patients with findings of resectable pancreatic cancer on computed tomography (CT). METHODS: All patients who presented to a tertiary referral centre with pancreatic cancer between April 2012 and December 2013 were included in the study. Patients with findings of resectable disease on CT underwent further liver diffusion-weighted MR imaging, using a hepatocyte-specific contrast agent. RESULTS: A total of 583 patients with pancreatic cancer were referred. 69 (11.8%) had resectable disease on CT. Of these 69 patients, 16 (23.2%) had liver metastases on MR imaging, while 6 (8.7%) had indeterminate lesions. Of the 16 patients with positive MR imaging findings of liver metastases, 11 died of pancreatic cancer, with a mean survival time of nine months (95% confidence interval [CI] 5.22-14.05). The mean survival time of the 47 patients with negative MR imaging findings was 16 months (95% CI 14.33-18.10; p = 0.001). Subsequently, 22 of these patients underwent surgery, and only 1 (4.5%) patient was found to have liver metastasis at surgery. CONCLUSION: The results of the present study indicate that MR imaging improves the staging of disease in patients with resectable pancreatic cancer. PMID- 27353742 TI - Enzyme-driven metabolomic screening: a proof-of-principle method for discovery of plant defence compounds targeted by pathogens. AB - Plants produce a variety of secondary metabolites to defend themselves from pathogen attack, while pathogens have evolved to overcome plant defences by producing enzymes that degrade or modify these defence compounds. However, many compounds targeted by pathogen enzymes currently remain enigmatic. Identifying host compounds targeted by pathogen enzymes would enable us to understand the potential importance of such compounds in plant defence and modify them to make them insensitive to pathogen enzymes. Here, a proof of concept metabolomics-based method was developed to discover plant defence compounds modified by pathogens using two pathogen enzymes with known targets in wheat and tomato. Plant extracts treated with purified pathogen enzymes were subjected to LC-MS, and the relative abundance of metabolites before and after treatment were comparatively analysed. Using two enzymes from different pathogens the in planta targets could be found by combining relatively simple enzymology with the power of untargeted metabolomics. Key to the method is dataset simplification based on natural isotope occurrence and statistical filtering, which can be scripted. The method presented here will aid in our understanding of plant-pathogen interactions and may lead to the development of new plant protection strategies. PMID- 27353740 TI - Pharmacological targeting of glucose-6-phosphate dehydrogenase in human erythrocytes by Bay 11-7082, parthenolide and dimethyl fumarate. AB - In mature erythrocytes, glucose-6-phosphate dehydrogenase (G6PDH) and 6 phosphogluconate dehydrogenase (6PGDH) yield NADPH, a crucial cofactor of the enzyme glutathione reductase (GR) converting glutathione disulfide (GSSG) into its reduced state (GSH). GSH is essential for detoxification processes in and survival of erythrocytes. We explored whether the anti-inflammatory compounds Bay 11-7082, parthenolide and dimethyl fumarate (DMF) were able to completely deplete a common target (GSH), and to impair the function of upstream enzymes of GSH recycling and replenishment. Treatment of erythrocytes with Bay 11-7082, parthenolide or DMF led to concentration-dependent eryptosis resulting from complete depletion of GSH. GSH depletion was due to strong inhibition of G6PDH activity. Bay 11-7082 and DMF, but not parthenolide, were able to inhibit the GR activity. This approach "Inhibitors, Detection of their common target that is completely depleted or inactivated when pharmacologically relevant concentrations of each single inhibitor are applied, Subsequent functional analysis of upstream enzymes for this target" (IDS), can be applied to a broad range of inhibitors and cell types according to the selected target. The specific G6PDH inhibitory effect of these compounds may be exploited for the treatment of human diseases with high NADPH and GSH consumption rates, including malaria, trypanosomiasis, cancer or obesity. PMID- 27353743 TI - Patients with COPD tell their stories about living with the long-term condition: an innovative and powerful way to impact primary health care professionals' attitudes and behaviour? AB - BACKGROUND: Sub-optimal adoption of evidence based practice by primary health care professionals (PHCPs) is affecting the health of people with chronic obstructive pulmonary disease (COPD). This paper shows how 'patient stories' were used to engineer professional and organisational change. METHODS: 'Stories' were transmitted via a pre-planned question and answer session involving patients and carers. The impact on PHCPs' attitudes and behaviour was explored through observing the session, open-text questionnaires completed by the PHCPs at the end of the session and clinician interviews. FINDINGS: The stories about living with COPD, told by patients and their carers, were found to be an innovative and powerful way to impact PHCPs' attitude and behaviour. Strong motivational context was created, in which clinicians were able to see the relevance of learning through active engagement with real people. CONCLUSION: Long term conditions such as COPD have long term implications for the daily lives of patients and their carers. Hearing about these consequences in 'the first person' is an influential training tool with a powerful impact on PHCPs' attitudes and behaviour. PMID- 27353744 TI - A rare cause of colonic thickening and lymphadenopathy. PMID- 27353745 TI - Chemical Coding of Sensory Neurons Supplying the Hip Joint Capsule in the Sheep. AB - Immunohistochemical properties of nerve fibres supplying the joint capsule were previously described in many mammalian species, but the localization of sensory neurons supplying this structure was studied only in laboratory animals, the rat and rabbit. However, there is no comprehensive data on the chemical coding of sensory neurons projecting to the hip joint capsule (HJC). The aim of this study was to establish immunohistochemical properties of sensory neurons supplying HJC in the sheep. The study was carried out on 10 sheep, weighing about 30-40 kg. The animals were injected with a retrograde neural tracer Fast Blue (FB) into HJC. Sections of the spinal ganglia (SpG) with FB-positive (FB+) neurons were stained using antibodies against calcitonin gene-related peptide (CGRP) substance P (SP), pituitary adenylate cyclase-activating peptide (PACAP), nitric oxide synthase (n NOS), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), Leu-5 enkephalin (Leu-Enk), galanin (GAL) and vesicular acetylcholine transporter (VACHT). The vast majority of FB+ neurons supplying HJC was found in the ganglia from the 5th lumbar to the 2nd sacral. Immunohistochemistry revealed that most of these neurons were immunoreactive to CGRP or SP (80.7 +/- 8.0% or 56.4 +/- 4.8%, respectively) and many of them stained for PACAP or GAL (52.9 +/- 2.9% or 50.6 +/ 19.7%, respectively). Other populations of FB+ neurons were those immunoreactive to n-NOS (37.8 +/- 9.7%), NPY (34.6 +/- 6.7%), VIP (28.7 +/- 4.8%), Leu-Enk (27.1 +/- 14.6) and VACHT (16.7 +/- 9.6). PMID- 27353746 TI - Fulminant liver failure resulting from massive hepatic infarction associated with hemolysis, elevated liver enzymes, and low platelets syndrome. AB - Hepatic infarction is an extremely rare and fatal complication associated with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. It can develop into fulminant liver failure, which increases both maternal and neonatal mortality rates. A 34-year-old woman with no remarkable past medical history developed eclampsia after delivery at 40 weeks of gestation. Imaging indicated massive hepatic infarction and rupture followed by cardiac arrest and fulminant liver failure. Despite liver replacement therapy with plasma exchange and continuous hemodiafiltration, the patient gradually deteriorated with persistent bacterial infection until death at 98 days after delivery. The management of fulminant liver failure complicated with HELLP syndrome should be multidisciplinary. Liver transplantation, the only radical treatment for fulminant liver failure, is worth attempting, if applicable. PMID- 27353747 TI - Children with Poor Reading Skills at the Word Level Show Reduced Fractional Anisotropy in White Matter Tracts of Both Hemispheres. AB - Diffusion tensor imaging (DTI) studies showed that microstructural alterations are correlated to reading skills. In this study, we aim to investigate white matter microstructure of a group of Portuguese speakers with poor reading level, using different parameters of DTI. To perform this analysis, we selected children ranging from 8 to 12 years of age, poor readers (n = 17) and good readers (n = 23), evaluated in the word-level ability based on a Latent Class Analysis (LCA) of Academic Performance Test (TDE). Poor readers exhibited significant fractional anisotropy (FA) reductions in many tracts of both hemispheres, but small and restricted clusters of increased radial diffusivity (RD) in the left hemisphere. Spatial coherence of fibers might be the main source of differences, as changes in FA were not similarly accompanied in terms of extension by changes in RD. Widespread structural alterations in the white matter could prevent good reading ability at word level, which is consistent with recent studies demonstrating the involvement of multiple cortical regions and white matter tracts in reading disabilities. PMID- 27353748 TI - Glycerol inhibits the primary pathways and transforms the secondary pathway of insulin aggregation. AB - Aggregation of insulin initiated from the monomeric form proceeds via the secondary pathway of fragmentation. It was interesting to find that glycerol had the potential to transform the secondary pathway of aggregation from fragmentation to heterogeneous nucleation in a concentration dependent manner. Such a change in the secondary pathway was manifested by a change in the fibrillar morphology, wherein, longer fibrils were formed in the presence of glycerol. Glycerol could inhibit all the major steps of insulin aggregation. The analysis of the kinetic traces suggested that the inhibitory effect was most significant on the primary pathways, although secondary nucleation and elongation were also inhibited. In fact, at higher glycerol concentrations, the primary pathways were inhibited to such an extent that the majority of the aggregation was now driven by the secondary pathways. Our data suggest that glycerol binds to the early intermediates in the insulin aggregation pathway, and inhibits them from forming the aggregation competent species capable of elongation. As higher order species are formed in the aggregation pathway, the relative stabilization rendered by glycerol diminishes due to the exclusion of glycerol from the interface. PMID- 27353749 TI - Properties of the feline tumour suppressor reduced expression in immortalized cells (REIC/Dkk-3). AB - Reduced expression in immortalized cells (REIC/Dkk-3), a member of the human Dickkopf (Dkk) family, is a growth suppressor in human and canine mammary tumours. Mammary gland tumours are common neoplasms with high malignancy in female cats. The purpose of this study was to clone the feline REIC/Dkk-3 homolog, investigate its expression in cell lines established from feline mammary gland tumours, and test its tumour suppressor function. Western blot analysis revealed that expression of the REIC/Dkk-3 protein was reduced in feline mammary carcinoma cell lines. Forced expression of REIC/Dkk-3 induced apoptosis in feline mammary tumour cell lines. These results demonstrate that REIC/Dkk-3 expression, which is downregulated in feline mammary tumour cell lines, results in the induction of apoptosis in these cells. Our findings suggest that feline REIC/Dkk 3 represents a potential molecular target for the development of therapies against feline mammary cancers. PMID- 27353750 TI - Longitudinal changes in Langerhans cell density of the cornea and conjunctiva in contact lens-induced dry eye. AB - BACKGROUND: The aim was to determine longitudinal changes in Langerhans cell density (LCD) in the human cornea and conjunctiva during asymptomatic and symptomatic contact lens wear. METHODS: Twenty-five participants with contact lens-induced dry eye (CLIDE) and 35 without CLIDE (NO-CLIDE), diagnosed using a range of symptom questionnaires and objective tests (tear film break up, cotton thread tear test and corneal staining) were enrolled. The central cornea and nasal bulbar conjunctiva were examined using a Heidelberg laser scanning confocal microscope at baseline and following one, four and 24 weeks wear of daily disposable hydrogel contact lenses. Twenty-three non-contact lens-wearing controls were also examined. Langerhans cells were counted manually from randomly selected images. RESULTS: In the cornea, mean and standard error of the mean LCD was greater after one week of lens wear in CLIDE (55 +/- 7 cells/mm2 ) versus NO CLIDE (43 +/- 4 cells/mm2 ) (p = 0.041) and controls (27 +/- 4 cells/mm2 ) (p < 0.001). LCD was also greater in NO-CLIDE versus controls (p = 0.010). At week 4, LCD was greater in CLIDE (41 +/- 6 cells/mm2 ) versus controls (27 +/- 4 cells/mm2 ) (p = 0.004). There were no other significant differences between groups at weeks four or 24. In the conjunctiva, LCD was greater after one week of lens wear in CLIDE (17 +/- 1 cells/mm2 ) (p = 0.003) and NO-CLIDE (17 +/- 3 cells/mm2 ) (p = 0.001) versus controls (7 +/- 1 cells/mm2 ). There were no significant differences between groups at weeks four or 24. CONCLUSIONS: The initial transient increase in corneal and conjunctival LCD in CLIDE (versus NO CLIDE) suggests an inflammatory component in the aetiology of this condition. PMID- 27353751 TI - Directed Binding of Gliding Bacterium, Mycoplasma mobile, Shown by Detachment Force and Bond Lifetime. AB - Mycoplasma mobile, a fish-pathogenic bacterium, features a protrusion that enables it to glide smoothly on solid surfaces at a velocity of up to 4.5 um s( 1) in the direction of the protrusion. M. mobile glides by a repeated catch-pull release of sialylated oligosaccharides fixed on a solid surface by hundreds of 50 nm flexible "legs" sticking out from the protrusion. This gliding mechanism may be explained by a possible directed binding of each leg with sialylated oligosaccharides, by which the leg can be detached more easily forward than backward. In the present study, we used a polystyrene bead held by optical tweezers to detach a starved cell at rest from a glass surface coated with sialylated oligosaccharides and concluded that the detachment force forward is 1.6- to 1.8-fold less than that backward, which may be linked to a catch bond like behavior of the cell. These results suggest that this directed binding has a critical role in the gliding mechanism. IMPORTANCE: Mycoplasma species are the smallest bacteria and are parasitic and occasionally commensal, as represented by Mycoplasma pneumoniae, which causes so-called "walking pneumonia" in humans. Dozens of species glide on host tissues, always in the direction of the characteristic cellular protrusion, by novel mechanisms. The fastest species, Mycoplasma mobile, catches, pulls, and releases sialylated oligosaccharides (SOs), which are common targets among influenza viruses, by means of a specific receptor based on the energy of ATP hydrolysis. Here, force measurements made with optical tweezers revealed that the force required to detach a cell from SOs is smaller forward than backward along the gliding direction. The directed binding should be a clue to elucidate this novel motility mechanism. PMID- 27353752 TI - Genomic Analysis and Comparison of Two Gonorrhea Outbreaks. AB - Gonorrhea is a sexually transmitted disease causing growing concern, with a substantial increase in reported incidence over the past few years in the United Kingdom and rising levels of resistance to a wide range of antibiotics. Understanding its epidemiology is therefore of major biomedical importance, not only on a population scale but also at the level of direct transmission. However, the molecular typing techniques traditionally used for gonorrhea infections do not provide sufficient resolution to investigate such fine-scale patterns. Here we sequenced the genomes of 237 isolates from two local collections of isolates from Sheffield and London, each of which was resolved into a single type using traditional methods. The two data sets were selected to have different epidemiological properties: the Sheffield data were collected over 6 years from a predominantly heterosexual population, whereas the London data were gathered within half a year and strongly associated with men who have sex with men. Based on contact tracing information between individuals in Sheffield, we found that transmission is associated with a median time to most recent common ancestor of 3.4 months, with an upper bound of 8 months, which we used as a criterion to identify likely transmission links in both data sets. In London, we found that transmission happened predominantly between individuals of similar age, sexual orientation, and location and also with the same HIV serostatus, which may reflect serosorting and associated risk behaviors. Comparison of the two data sets suggests that the London epidemic involved about ten times more cases than the Sheffield outbreak. IMPORTANCE: The recent increases in gonorrhea incidence and antibiotic resistance are cause for public health concern. Successful intervention requires a better understanding of transmission patterns, which is not uncovered by traditional molecular epidemiology techniques. Here we studied two outbreaks that took place in Sheffield and London, United Kingdom. We show that whole-genome sequencing provides the resolution to investigate direct gonorrhea transmission between infected individuals. Combining genome sequencing with rich epidemiological information about infected individuals reveals the importance of several transmission routes and risk factors, which can be used to design better control measures. PMID- 27353753 TI - Targeting Alpha Toxin and ClfA with a Multimechanistic Monoclonal-Antibody-Based Approach for Prophylaxis of Serious Staphylococcus aureus Disease. AB - Staphylococcus aureus produces numerous virulence factors, each contributing different mechanisms to bacterial pathogenesis in a spectrum of diseases. Alpha toxin (AT), a cytolytic pore-forming toxin, plays a key role in skin and soft tissue infections and pneumonia, and a human anti-AT monoclonal antibody (MAb), MEDI4893*, has been shown to reduce disease severity in dermonecrosis and pneumonia infection models. However, interstrain diversity and the complex pathogenesis of S. aureus bloodstream infections suggests that MEDI4893* alone may not provide adequate protection against S. aureus sepsis. Clumping factor A (ClfA), a fibrinogen binding protein, is an important virulence factor facilitating S. aureus bloodstream infections. Herein, we report on the identification of a high-affinity anti-ClfA MAb, 11H10, that inhibits ClfA binding to fibrinogen, prevents bacterial agglutination in human plasma, and promotes opsonophagocytic bacterial killing (OPK). 11H10 prophylaxis reduced disease severity in a mouse bacteremia model and was dependent on Fc effector function and OPK. Additionally, prophylaxis with 11H10 in combination with MEDI4893* provided enhanced strain coverage in this model and increased survival compared to that obtained with the individual MAbs. The MAb combination also reduced disease severity in murine dermonecrosis and pneumonia models, with activity similar to that of MEDI4893* alone. These results indicate that an MAb combination targeting multiple virulence factors provides benefit over a single MAb neutralizing one virulence mechanism by providing improved efficacy, broader strain coverage, and protection against multiple infection pathologies. IMPORTANCE: Alternative strategies to broad-spectrum antibiotics are required to combat the antibiotic resistance epidemic. Previous attempts at active or passive immunization against Staphylococcus aureus targeting single antigens have failed in clinical trials despite positive preclinical data. To provide broad disease and isolate coverage, an effective immunization strategy likely must target multiple virulence mechanisms of the pathogen. Herein, we tested a multimechanistic MAb combination targeting alpha toxin (AT) and clumping factor A (ClfA) that neutralizes AT-mediated cytotoxicity, blocks fibrinogen binding by ClfA, prevents bacterial agglutination, targets the bacteria for opsonophagocytic killing, and provides broad isolate coverage in a lethal-bacteremia model. Although each MAb alone was effective in bacteremia against some individual isolates, the MAb combination provided improved protection against other isolates. These results illustrate the importance of targeting multiple virulence mechanisms and highlight the potential for an MAb combination targeting AT and ClfA to effectively prevent S. aureus disease. PMID- 27353754 TI - Light Regimes Shape Utilization of Extracellular Organic C and N in a Cyanobacterial Biofilm. AB - Although it is becoming clear that many microbial primary producers can also play a role as organic consumers, we know very little about the metabolic regulation of photoautotroph organic matter consumption. Cyanobacteria in phototrophic biofilms can reuse extracellular organic carbon, but the metabolic drivers of extracellular processes are surprisingly complex. We investigated the metabolic foundations of organic matter reuse by comparing exoproteome composition and incorporation of (13)C-labeled and (15)N-labeled cyanobacterial extracellular organic matter (EOM) in a unicyanobacterial biofilm incubated using different light regimes. In the light and the dark, cyanobacterial direct organic C assimilation accounted for 32% and 43%, respectively, of all organic C assimilation in the community. Under photosynthesis conditions, we measured increased excretion of extracellular polymeric substances (EPS) and proteins involved in micronutrient transport, suggesting that requirements for micronutrients may drive EOM assimilation during daylight hours. This interpretation was supported by photosynthesis inhibition experiments, in which cyanobacteria incorporated N-rich EOM-derived material. In contrast, under dark, C-starved conditions, cyanobacteria incorporated C-rich EOM-derived organic matter, decreased excretion of EPS, and showed an increased abundance of degradative exoproteins, demonstrating the use of the extracellular domain for C storage. Sequence-structure modeling of one of these exoproteins predicted a specific hydrolytic activity that was subsequently detected, confirming increased EOM degradation in the dark. Associated heterotrophic bacteria increased in abundance and upregulated transport proteins under dark relative to light conditions. Taken together, our results indicate that biofilm cyanobacteria are successful competitors for organic C and N and that cyanobacterial nutrient and energy requirements control the use of EOM. IMPORTANCE: Cyanobacteria are globally distributed primary producers, and the fate of their fixed C influences microbial biogeochemical cycling. This fate is complicated by cyanobacterial degradation and assimilation of organic matter, but because cyanobacteria are assumed to be poor competitors for organic matter consumption, regulation of this process is not well tested. In mats and biofilms, this is especially relevant because cyanobacteria produce an extensive organic extracellular matrix, providing the community with a rich source of nutrients. Light is a well-known regulator of cyanobacterial metabolism, so we characterized the effects of light availability on the incorporation of organic matter. Using stable isotope tracing at the single-cell level, we quantified photoautotroph assimilation under different metabolic conditions and integrated the results with proteomics to elucidate metabolic status. We found that cyanobacteria effectively compete for organic matter in the light and the dark and that nutrient requirements and community interactions contribute to cycling of extracellular organic matter. PMID- 27353756 TI - Plasmid Dynamics in KPC-Positive Klebsiella pneumoniae during Long-Term Patient Colonization. AB - Carbapenem-resistant Klebsiella pneumoniae strains are formidable hospital pathogens that pose a serious threat to patients around the globe due to a rising incidence in health care facilities, high mortality rates associated with infection, and potential to spread antibiotic resistance to other bacterial species, such as Escherichia coli Over 6 months in 2011, 17 patients at the National Institutes of Health (NIH) Clinical Center became colonized with a highly virulent, transmissible carbapenem-resistant strain of K. pneumoniae Our real-time genomic sequencing tracked patient-to-patient routes of transmission and informed epidemiologists' actions to monitor and control this outbreak. Two of these patients remained colonized with carbapenemase-producing organisms for at least 2 to 4 years, providing the opportunity to undertake a focused genomic study of long-term colonization with antibiotic-resistant bacteria. Whole-genome sequencing studies shed light on the underlying complex microbial colonization, including mixed or evolving bacterial populations and gain or loss of plasmids. Isolates from NIH patient 15 showed complex plasmid rearrangements, leaving the chromosome and the blaKPC-carrying plasmid intact but rearranging the two other plasmids of this outbreak strain. NIH patient 16 has shown continuous colonization with blaKPC-positive organisms across multiple time points spanning 2011 to 2015. Genomic studies defined a complex pattern of succession and plasmid transmission across two different K. pneumoniae sequence types and an E. coli isolate. These findings demonstrate the utility of genomic methods for understanding strain succession, genome plasticity, and long-term carriage of antibiotic-resistant organisms. IMPORTANCE: In 2011, the NIH Clinical Center had a nosocomial outbreak involving 19 patients who became colonized or infected with blaKPC-positive Klebsiella pneumoniae Patients who have intestinal colonization with blaKPC-positive K. pneumoniae are at risk for developing infections that are difficult or nearly impossible to treat with existing antibiotic options. Two of those patients remained colonized with blaKPC-positive Klebsiella pneumoniae for over a year, leading to the initiation of a detailed genomic analysis exploring mixed colonization, plasmid recombination, and plasmid diversification. Whole genome sequence analysis identified a variety of changes, both subtle and large, in the blaKPC-positive organisms. Long-term colonization of patients with blaKPC positive Klebsiella pneumoniae creates new opportunities for horizontal gene transfer of plasmids encoding antibiotic resistance genes and poses complications for the delivery of health care. PMID- 27353755 TI - Overexpression of Plasmodium berghei ATG8 by Liver Forms Leads to Cumulative Defects in Organelle Dynamics and to Generation of Noninfectious Merozoites. AB - Plasmodium parasites undergo continuous cellular renovation to adapt to various environments in the vertebrate host and insect vector. In hepatocytes, Plasmodium berghei discards unneeded organelles for replication, such as micronemes involved in invasion. Concomitantly, intrahepatic parasites expand organelles such as the apicoplast that produce essential metabolites. We previously showed that the ATG8 conjugation system is upregulated in P. berghei liver forms and that P. berghei ATG8 (PbATG8) localizes to the membranes of the apicoplast and cytoplasmic vesicles. Here, we focus on the contribution of PbATG8 to the organellar changes that occur in intrahepatic parasites. We illustrated that micronemes colocalize with PbATG8-containing structures before expulsion from the parasite. Interference with PbATG8 function by overexpression results in poor development into late liver stages and production of small merosomes that contain immature merozoites unable to initiate a blood infection. At the cellular level, PbATG8 overexpressing P. berghei exhibits a delay in microneme compartmentalization into PbATG8-containing autophagosomes and elimination compared to parasites from the parental strain. The apicoplast, identifiable by immunostaining of the acyl carrier protein (ACP), undergoes an abnormally fast proliferation in mutant parasites. Over time, the ACP staining becomes diffuse in merosomes, indicating a collapse of the apicoplast. PbATG8 is not incorporated into the progeny of mutant parasites, in contrast to parental merozoites in which PbATG8 and ACP localize to the apicoplast. These observations reveal that Plasmodium ATG8 is a key effector in the development of merozoites by controlling microneme clearance and apicoplast proliferation and that dysregulation in ATG8 levels is detrimental for malaria infectivity. IMPORTANCE: Malaria is responsible for more mortality than any other parasitic disease. Resistance to antimalarial medicines is a recurring problem; new drugs are urgently needed. A key to the parasite's successful intracellular development in the liver is the metabolic changes necessary to convert the parasite from a sporozoite to a replication-competent, metabolically active trophozoite form. Our study reinforces the burgeoning concept that organellar changes during parasite differentiation are mediated by an autophagy like process. We have identified ATG8 in Plasmodium liver forms as an important effector that controls the development and fate of organelles, e.g., the clearance of micronemes that are required for hepatocyte invasion and the expansion of the apicoplast that produces many metabolites indispensable for parasite replication. Given the unconventional properties and the importance of ATG8 for parasite development in hepatocytes, targeting the parasite's autophagic pathway may represent a novel approach to control malarial infections. PMID- 27353757 TI - Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth. AB - Preterm birth increases the risk of adverse birth outcomes and is the leading cause of neonatal mortality. A significant cause of preterm birth is in utero infection with vaginal microorganisms. These vaginal microorganisms are often recovered from the amniotic fluid of preterm birth cases. A vaginal microorganism frequently associated with preterm birth is group B streptococcus (GBS), or Streptococcus agalactiae However, the molecular mechanisms underlying GBS ascension are poorly understood. Here, we describe the role of the GBS hyaluronidase in ascending infection and preterm birth. We show that clinical GBS strains associated with preterm labor or neonatal infections have increased hyaluronidase activity compared to commensal strains obtained from rectovaginal swabs of healthy women. Using a murine model of ascending infection, we show that hyaluronidase activity was associated with increased ascending GBS infection, preterm birth, and fetal demise. Interestingly, hyaluronidase activity reduced uterine inflammation but did not impact placental or fetal inflammation. Our study shows that hyaluronidase activity enables GBS to subvert uterine immune responses, leading to increased rates of ascending infection and preterm birth. These findings have important implications for the development of therapies to prevent in utero infection and preterm birth. IMPORTANCE: GBS are a family of bacteria that frequently colonize the vagina of pregnant women. In some cases, GBS ascend from the vagina into the uterine space, leading to fetal injury and preterm birth. Unfortunately, little is known about the mechanisms underlying ascending GBS infection. In this study, we show that a GBS virulence factor, HylB, shows higher activity in strains isolated from cases of preterm birth than those isolates from rectovaginal swabs of healthy women. We discovered that GBS rely on HylB to avoid immune detection in uterine tissue, but not placental tissue, which leads to increased rates of fetal injury and preterm birth. These studies provide novel insight into the underlying mechanisms of ascending infection. PMID- 27353758 TI - A Commensal Bacterium Promotes Virulence of an Opportunistic Pathogen via Cross Respiration. AB - Bacteria rarely inhabit infection sites alone, instead residing in diverse, multispecies communities. Despite this fact, bacterial pathogenesis studies primarily focus on monoculture infections, overlooking how community interactions influence the course of disease. In this study, we used global mutant fitness profiling (transposon sequencing [Tn-seq]) to determine the genetic requirements for the pathogenic bacterium Aggregatibacter actinomycetemcomitans to cause disease when coinfecting with the commensal bacterium Streptococcus gordonii Our results show that S. gordonii extensively alters A. actinomycetemcomitans requirements for virulence factors and biosynthetic pathways during infection. In addition, we discovered that the presence of S. gordonii enhances the bioavailability of oxygen during infection, allowing A. actinomycetemcomitans to shift from a primarily fermentative to a respiratory metabolism that enhances its growth yields and persistence. Mechanistically, respiratory metabolism enhances the fitness of A. actinomycetemcomitans in vivo by increasing ATP yields via central metabolism and creating a proton motive force. Our results reveal that, similar to cross-feeding, where one species provides another species with a nutrient, commensal bacteria can also provide electron acceptors that promote the respiratory growth and fitness of pathogens in vivo, an interaction that we term cross-respiration. IMPORTANCE: Commensal bacteria can enhance the virulence of pathogens in mixed-species infections. However, knowledge of the mechanisms underlying this clinically relevant phenomenon is lacking. To bridge this gap, we comprehensively determined the genes a pathogen needs to establish coinfection with a commensal. Our findings show that the metabolism of the pathogen is low energy-yielding in monoinfection, but in coinfection, the commensal improves the fitness of the pathogen by increasing the bioavailability of oxygen, thereby shifting the pathogen toward a high-energy-yielding metabolism. Similar to cross feeding, this interaction, which we term cross-respiration, illustrates that commensal bacteria can provide electron acceptors that enhance the virulence of pathogens during infection. PMID- 27353759 TI - Dengue Virus Genome Uncoating Requires Ubiquitination. AB - The process of genome release or uncoating after viral entry is one of the least studied steps in the flavivirus life cycle. Flaviviruses are mainly arthropod borne viruses, including emerging and reemerging pathogens such as dengue, Zika, and West Nile viruses. Currently, dengue virus is one of the most significant human viral pathogens transmitted by mosquitoes and is responsible for about 390 million infections every year around the world. Here, we examined for the first time molecular aspects of dengue virus genome uncoating. We followed the fate of the capsid protein and RNA genome early during infection and found that capsid is degraded after viral internalization by the host ubiquitin-proteasome system. However, proteasome activity and capsid degradation were not necessary to free the genome for initial viral translation. Unexpectedly, genome uncoating was blocked by inhibiting ubiquitination. Using different assays to bypass entry and evaluate the first rounds of viral translation, a narrow window of time during infection that requires ubiquitination but not proteasome activity was identified. In this regard, ubiquitin E1-activating enzyme inhibition was sufficient to stabilize the incoming viral genome in the cytoplasm of infected cells, causing its retention in either endosomes or nucleocapsids. Our data support a model in which dengue virus genome uncoating requires a nondegradative ubiquitination step, providing new insights into this crucial but understudied viral process. IMPORTANCE: Dengue is the most significant arthropod-borne viral infection in humans. Although the number of cases increases every year, there are no approved therapeutics available for the treatment of dengue infection, and many basic aspects of the viral biology remain elusive. After entry, the viral membrane must fuse with the endosomal membrane to deliver the viral genome into the cytoplasm for translation and replication. A great deal of information has been obtained in the last decade regarding molecular aspects of the fusion step, but little is known about the events that follow this process, which leads to viral RNA release from the nucleocapsid. Here, we investigated the fate of nucleocapsid components (capsid protein and viral genome) during the infection process and found that capsid is degraded by the ubiquitin-proteasome system. However, in contrast to that observed for other RNA and DNA viruses, dengue virus capsid degradation was not responsible for genome uncoating. Interestingly, we found that dengue virus genome release requires a nondegradative ubiquitination step. These results provide the first insights into dengue virus uncoating and present new opportunities for antiviral intervention. PMID- 27353760 TI - The Brazilian Dilemma: Increased Scientific Production and High Publication Costs during a Global Health Crisis and Major Economic Downturn. PMID- 27353761 TI - Erratum for O'Neill et al., Cytosolic Replication of Group A Streptococcus in Human Macrophages. PMID- 27353762 TI - Erratum for Ben Zakour et al., Sequential Acquisition of Virulence and Fluoroquinolone Resistance Has Shaped the Evolution of Escherichia coli ST131. PMID- 27353763 TI - In the Limelight: Photoreceptors in Cyanobacteria. AB - Certain cyanobacteria look green if grown in red light and vice versa. This dramatic color change, called complementary chromatic adaptation (CCA), is caused by alterations of the major colored light-harvesting proteins. A major controller of CCA is the cyanobacteriochrome (CBCR) RcaE, a red-green reversible photoreceptor that triggers a complex signal transduction pathway. Now, a new study demonstrates that CCA is also modulated by DpxA, a CBCR that senses yellow and teal (greenish blue) light. DpxA acts to expand the range of wavelengths that can impact CCA, by fine-tuning the process. This dual control of CCA might positively impact the fitness of cells growing in the shade of competing algae or in a water column where light levels and spectral quality change gradually with depth. This discovery adds to the growing number of light-responsive phenomena controlled by multiple CBCRs. Furthermore, the diverse CBCRs which are exclusively found in cyanobacteria have significant biotechnological potential. PMID- 27353764 TI - alpha-Galactosidase delivery using 30Kc19-human serum albumin nanoparticles for effective treatment of Fabry disease. AB - Fabry disease is a genetic lysosomal storage disease caused by deficiency of alpha-galactosidase, the enzyme-degrading neutral glycosphingolipid that is transported to lysosome. Glycosphingolipid accumulation by this disease causes multi-organ dysfunction and premature death of the patient. Currently, enzyme replacement therapy (ERT) using recombinant alpha-galactosidase is the only treatment available for Fabry disease. To maximize the efficacy of treatment, enhancement of cellular delivery and enzyme stability is a challenge in ERT using alpha-galactosidase. In this study, protein nanoparticles using human serum albumin (HSA) and 30Kc19 protein, originating from silkworm, were used to enhance the delivery and intracellular alpha-galactosidase stability. 30Kc19-HSA nanoparticles loaded with the alpha-galactosidase were formed by desolvation method. 30Kc19-HSA nanoparticles had a uniform spherical shape and were well dispersed in cell culture media. 30Kc19-HSA nanoparticles had negligible toxicity to human cells. The nanoparticles exhibited enhanced cellular uptake and intracellular stability of delivered alpha-galactosidase in human foreskin fibroblast. Additionally, they showed enhanced globotriaosylceramide degradation in Fabry patients' fibroblasts. It is expected that 30Kc19-HSA protein nanoparticles could be used as an effective tool for efficient delivery and enhanced stability of drugs. PMID- 27353766 TI - ATP sensitive potassium channel openers: A new class of ocular hypotensive agents. PMID- 27353767 TI - Comparison of Free Light Chain Assays: Freelite and N Latex in Diagnosis, Monitoring, and Predicting Survival in Light Chain Amyloidosis. AB - OBJECTIVES: Measurement of serum free light chains (FLCs) is critical in diagnosis, prognosis, and monitoring treatment responses in light chain (AL) amyloidosis. We compare the Freelite assay (polyclonal antibodies to hidden light chain epitopes), which is the current gold standard, with a new assay: a mixture of monoclonal antibodies to light chain epitopes (N Latex). METHODS: We collected 240 serum samples from 94 consecutive patients with newly diagnosed AL amyloidosis (at least three serial serum samples during the first 6 months) analyzed at the National Amyloidosis Centre, London, from January 2011 to April 2012. Concordance in detecting abnormal light chain components and hematologic response was assessed at 2, 4, and 6 months. RESULTS: The kappa and lambda clonal light chain involvement was 21% and 79%, respectively, with an abnormal kappa/lambda ratio or detectable protein in 78.7%. Median kappa, lambda, and difference in involved and uninvolved FLCs by Freelite and N Latex assays were 17.3 vs 16 mg/L (R(2 ) = 0.91), 48.8 vs 52.6 mg/L (R(2) = 0.52), and 43.2 vs 39.1 mg/L, respectively. Discordant kappa/lambda ratios at presentation were as follows: 10 of 90 abnormal by Freelite/normal by N Latex and 11 of 90 abnormal by N Latex/normal by Freelite. CONCLUSIONS: Both FLC assays show good correlation in detecting the abnormal light chain subtype with discordance in absolute values and thus are not interchangeable. PMID- 27353765 TI - Growth differentiation factor-15 promotes glutamate release in medial prefrontal cortex of mice through upregulation of T-type calcium channels. AB - Growth differentiation factor-15 (GDF-15) has been implicated in ischemic brain injury and synapse development, but its involvement in modulating neuronal excitability and synaptic transmission remain poorly understood. In this study, we investigated the effects of GDF-15 on non-evoked miniature excitatory post synaptic currents (mEPSCs) and neurotransmitter release in the medial prefrontal cortex (mPFC) in mice. Incubation of mPFC slices with GDF-15 for 60 min significantly increased the frequency of mEPSCs without effect on their amplitude. GDF-15 also significantly elevated presynaptic glutamate release, as shown by HPLC. These effects were blocked by dual TGF-beta type I receptor (TbetaRI) and TGF-beta type II receptor (TbetaRII) antagonists, but not by a TbetaRI antagonist alone. Meanwhile, GDF-15 enhanced pERK level, and inhibition of MAPK/ERK activity attenuated the GDF-15-induced increases in mEPSC and glutamate release. Blocking T-type calcium channels reduced the GDF-15 induced up regulation of synaptic transmission. Membrane-protein extraction and use of an intracellular protein-transport inhibitor showed that GDF-15 promoted CaV3.1 and CaV3.3 alpha-subunit expression by trafficking to the membrane. These results confirm previous findings in cerebellar granule neurons, in which GDF-15 induces its neurobiological effects via TbetaRII and activation of the ERK pathway, providing novel insights into the mechanism of GDF-15 function in cortical neurons. PMID- 27353768 TI - Bone Marrow Conventional Karyotyping and Fluorescence In Situ Hybridization: Defining an Effective Utilization Strategy for Evaluation of Myelodysplastic Syndromes. AB - OBJECTIVES: The current standard of practice for evaluation of myelodysplastic syndromes (MDS) includes peripheral blood and bone marrow morphology review and conventional karyotyping. Karyotype provides a global view of the chromosome complement while fluorescence in situ hybridization (FISH) targets specific abnormalities. The aim of this study was to determine if an MDS-FISH panel would add value beyond karyotype in MDS workup. METHODS: We studied 505 patients who were evaluated for a possible MDS and had concurrent bone marrow examination, karyotyping, and MDS-FISH performed. RESULTS: In total, 462 cases had adequate karyotyping (>=20 metaphases) and showed excellent concordance (96%, 445/462) between karyotyping and MDS-FISH. Additional FISH abnormalities had no impact on diagnosis and minimal impact on the cytogenetic prognostic scoring in the myeloid neoplasm cases (2%, 4/206). The concordance rate dropped to 82% (32/39) in the group with insufficient karyotyping (<20 metaphases), and additional FISH findings in this subgroup had no impact on the diagnosis but altered the cytogenetic prognostic scoring in 10% (2/20) of myeloid neoplasm cases. CONCLUSIONS: In the evaluation of a possible MDS, FISH rarely provides additional value when karyotype is adequate. We propose a value-based, cost-effective algorithmic approach for conventional karyotyping and FISH testing in routine MDS workup. PMID- 27353769 TI - Safety and efficacy of intra-articular injections of a combination of hyaluronic acid and mannitol (HAnOX-M) in patients with symptomatic knee osteoarthritis: Results of a double-blind, controlled, multicenter, randomized trial. AB - BACKGROUND: To compare both safety and efficacy of a novel intra-articular viscosupplement made of intermediate molecular weight (MW) hyaluronic acid (HA) mixed with high concentration of mannitol with a marketed high MW HA, in patients with knee osteoarthritis (OA). METHODS: Patients with symptomatic knee OA, with radiological OARSI grades 1 to 3, were enrolled in a controlled, double-blind, parallel-group, non-inferiority trial. They were randomized to receive three intra-articular injections, at weekly intervals, of either HAnOX-M made of a combination of HA (MW one to 1.5MDa, 31mg/2ml) and mannitol (70mg/2ml) or Bio-HA (MW 2.3 to 3.6MDa, 20mg/2ml). The primary outcome was six-month change in the WOMAC pain subscale (0 to 20). Sample size was calculated according to a non inferiority margin of 1.35. Secondary endpoints included six-month change in function and walking pain, analgesic consumption and safety. RESULTS: The intention-to-treat (ITT) and per-protocol (PP) populations consisted of 205 and 171 patients. HAnOX-M and Bio-Ha groups did not differ statistically at baseline. The primary analysis was conducted in the PP population, then in the ITT population. The average WOMAC pain score at baseline was 9.5 in both groups. Mean (SD) variations in WOMAC pain score were -4.4 (3.8) and -4.5 (4.3) mm, for HAnOX and Bio-HA respectively, satisfying the claim for non-inferiority. Similar results were obtained for all other secondary endpoints. CONCLUSION: Treatment with of HAnOX-M is effective to alleviate knee OA symptoms and to improve joint function over six months, with similar safety than conventional HA viscosupplement. PMID- 27353770 TI - Enhanced expression of long non-coding RNA Sox2ot promoted cell proliferation and motility in colorectal cancer. AB - BACKGROUND: Colorectal cancer (CRC) is one of the most common carcinomas throughout the world. Although the diagnostic and therapeutic strategies have made some progression in the treatment of CRC patients, the mortality of CRC remains relatively high. Hence, it is an urgency to find out the detailed mechanisms of how CRC occurs. METHODS: LncRNA Sox2ot expression was explored in CRC tissues and cell lines by using quantitative real-time PCR (qRT-PCR). Cell proliferation, migration and invasion ability was measured following downregulated expression of lncRNA Sox2ot by siRNA in CRC cells. Furthermore, western blot was used to detected the expression of Cyclin B1, Cdc 25C, N cadherin, and E-cadherin in si-Sox2ot transfected CRC cells. RESULTS: We found that lncRNA Sox2ot was increased in CRC tissues and cell lines. High expression of Sox2ot was associated with the progression of CRC patients. Decreased Sox2ot expression inhibited the proliferation capacity and caused cell cycle arrested in G0/G1 phase in CRC cells. The key cell cycle regulators Cyclin B1 and Cdc 25C were consistently downregulated by knockdown of Sox2ot. Furthermore, knockdown of Sox2ot suppressed cell migration and invasion and decreased the expression of mesenchymal protein N-cadherin, while it increased the expression of epithelial protein E-cadherin in CRC cells. CONCLUSIONS: LncRNA Sox2ot could promoted CRC cell proliferation and motility and associated with the outcome of CRC patients, suggesting Sox2ot could serve as a potential therapeutic target in the treatment of CRC. PMID- 27353772 TI - A new look for an evolving profession. PMID- 27353771 TI - Hepatocellular carcinoma: diagnosis and proposal of treatment. AB - Hepatocellular carcinoma (HCC) ranks third among the causes of cancer deaths globally. The most frequent causes are the hepatitis C virus (HCV), a combination of alcohol/HCV and metabolic syndrome (MS). The introduction of new pharmaceutical drugs that inhibit protease will bring a relative increase in the number of cases of HCC that are linked to the consumption of alcohol and MS. The latest development in the diagnostic sector is the total recognition of the contrast-enhanced ultrasound diagnostic algorithm. In the treatment sector we are moving on from the Barcelona criteria. With nodules up to 3 cm in size and with favorable anatomical and clinical conditions, the first treatment choice is percutaneous ablation. The first choice for nodules that are 3-5 cm in size is still hepatic resection (HR). For cases that fall completely within the Milan criteria with portal hypertension and compromised liver function the first treatment choice, in the total absence of any contraindications, is certainly LT. Intermediate forms of HCC are the most complicated as the stratification of patients is particularly relevant. TACE certainly no longer represents the only choice. HR is preferable where possible. According to the individual case and during down-staging, LT may be proposed. In some cases both locoregional ablative approaches and sorafenib can be used. In advanced cases with preserved function, the best treatment is still sorafenib. The treatment of HCC is complex because of the extreme anatomic-clinical variability of the cases. The key to a successful and effective approach is the creation of a true multi-disciplinary group in which the various players have the opportunity to express their own opinion. This is an indispensable prerequisite for a successful synthesis. PMID- 27353773 TI - Social care placements should become compulsory. PMID- 27353774 TI - Staff want training to deal with abuse. PMID- 27353776 TI - LGBT people mistrust services. PMID- 27353777 TI - Queen Margaret University to offer master's degree in person-centred practice. PMID- 27353778 TI - Mental health lead is nurse of the year 2016. PMID- 27353779 TI - With their enthusiasm, vanguards show the way in older people's care. PMID- 27353782 TI - Leading Change, Adding Value. PMID- 27353783 TI - Carers are not always seeking out the support they may need. PMID- 27353784 TI - Role of genetic factors in pain after hip replacement. PMID- 27353785 TI - Higher potato intake associated with hypertension risk. PMID- 27353786 TI - All that glisters.... PMID- 27353787 TI - The great indoors can work wonders. PMID- 27353788 TI - Advance care plans. PMID- 27353789 TI - Identifying and responding to gaps in domestic abuse services for older women. AB - Domestic abuse is widespread and indiscriminate. Older women living with domestic abuse report more health-related concerns than any other group, and demonstrate a higher incidence of significant mental health issues. Research suggests that older women who have experienced domestic abuse are not having their psychological and physical support needs met by existing services. This article examines the physical and mental health issues that older women face as a result of abusive relationships, and the barriers to seeking help. Multidisciplinary healthcare professionals can facilitate the therapeutic engagement of older women living with domestic abuse. Refuges and related interventions are limited in terms of the support they can offer, however, research suggests that developing a stepped approach, tailored to suit older women's needs, could be beneficial. PMID- 27353790 TI - Primary hyperparathyroidism and the role of the nurse. AB - Primary hyperparathyroidism is a common endocrine disorder that results in elevated levels of parathyroid hormone and subsequent hypercalcaemia. Nurses have an important role in the support, education and care of the older person undergoing surgical or conservative treatment. Knowledge of pathophysiology is essential to ensure complications of hyperparathyroidism are identified promptly and managed appropriately alongside existing healthcare needs. PMID- 27353791 TI - Supporting people with dementia to eat. AB - The aim of this systematic review was to identify the best ways of supporting people with dementia to eat. Five electronic databases were searched, with a date range from January 2004 to July 2015. Following screening of the 233 studies identified, 22 were included in the final analysis. The study interventions focused on educational programmes, environmental or routine changes, and assistance with eating, with the strongest evidence shown in the more complex educational programmes for people with dementia. The evidence suggests that staff who support people with dementia to eat should undertake face-to-face education programmes and aim to give people enough time when helping them to eat. However, cultural change may be needed to ensure individual assessments are carried out to identify those having difficulty eating, and to ensure they are afforded enough time to eat their meals. PMID- 27353792 TI - No one achieves change alone. PMID- 27353794 TI - Reducing risk of mosquito-borne infections. PMID- 27353795 TI - Project looks at success of same-day discharge. PMID- 27353796 TI - Barriers to good health care. PMID- 27353797 TI - Increased Dickkopf-1 expression is correlated with poisoning severity in carbon monoxide-poisoned humans and rats. AB - CONTEXT: Carbon monoxide (CO) poisoning results in neuronal injury. The expression of Dickkopf-1 (DKK-1) has not been investigated previously after CO poisoning. OBJECTIVE: The current study aimed to investigate the DKK-1 expression levels in humans and rats with acute CO poisoning and to analyze their correlation with poisoning severity. MATERIALS AND METHODS: We measured serum DKK 1 levels in patients with acute CO poisoning (n = 94) and in healthy controls (n = 90). On admission, a poisoning severity score (PSS) was determined for each patient. In addition, 36 male Sprague-Dawley rats were randomly assigned into three groups: (a) Sham group, (b) Low CO group and (c) High CO group. At 2 h after CO poisoning, DKK-1 expression and histopathological damage in the hippocampal tissues were measured. RESULTS: Serum DKK-1 levels were significantly higher in the acute CO-poisoned patients, compared to the healthy controls. Serum DKK-1 levels were significantly higher in the CO-poisoned patients with a lower PSS. In rats, CO poisoning induced significant upregulation of the gene and protein expression of DKK-1 in hippocampal tissues. Moreover, there was a positive correlation between DKK-1 levels and the degree of damage in the hippocampal tissues. DISCUSSION: DKK-1 induction in neurons after CO poisoning causes further neuronal injury. The severity of acute CO poisoning in rat models is associated with elevated serum DKK-1 levels and its upregulation in the brain tissue. CONCLUSION: DKK-1 appears to have potential utility in providing valuable information for determining the severity and damage of CO poisoning. PMID- 27353798 TI - Genotyping might help therapeutic decision-making in patients with von Willebrand disease type 2 B. PMID- 27353799 TI - Building nursing and midwifery leadership capacity in the Pacific. AB - AIM: The Australian Award Fellowship Program aimed to strengthen nursing and midwifery leadership and capacity in developing countries in the Pacific. BACKGROUND: It is necessary to build an optimal global health workforce, and leadership and mentorship are central to this need. This is especially important in small island states such as the Pacific who have limited capacity and resources. INTRODUCTION: This health system strengthening program addressed quality improvement in education, through the mentorship of potential nursing and midwifery leaders in the South Pacific Region. METHODS: Program participants between 2013 and 2015 were interviewed. Data were audio-taped, transcribed and analysed thematically using an inductive process. RESULTS: Thirty-four nurses and midwives from 12 countries participated. There were four main themes arising from the data which were: having a country-wide objective, learning how to be a leader, negotiating barriers and having effective mentorship. DISCUSSION: Our study showed that participants deemed their mentorship from country leaders highly valuable in relation to completing their projects, networking and role modelling. Similar projects are described. LIMITATIONS: The limitation of this study was its small size. There is a need to continue to build the momentum of the program and Fellows in each country in order to build regional networks. CONCLUSIONS AND IMPLICATIONS FOR NURSING AND MIDWIFERY: The Program has provided beneficial leadership education and mentorship for nurses and midwives from Pacific countries. It has provided a platform to develop quality improvement projects in line with national priorities. IMPLICATIONS FOR HEALTH POLICY: Global aid programs and the recipients of the program would benefit from comparable health strengthening approaches to nursing and midwifery in similar developing countries. PMID- 27353800 TI - Trypan blue as an affordable marker for automated live-dead cell analysis in image cytometry. AB - The aim of the present study was to combine image cytometry and trypan blue (TB) exclusion staining for a reproducible high-throughput detection of dead cells, enabling TB as an inexpensive marker, to be affordable for many studies and creating the possibility to combine fluorochromes without or with less spectral overlap. Capillary blood was drawn from a healthy volunteer, red blood cells were lysed and leukocyte cell death was induced. Samples were stained with CD45-FITC, CD14-PE, TB and DAPI, and then analyzed using image cytometry (iCys). TB quenching control tests were performed using DAPI and CD45-FITC. Images were generated in .TIF and .JPEG format using iCys image cytometer. The images were analyzed using CellProfiler (CP) modules to optimize the analysis based on the aims of each phase of this study. CellProfiler Analyst (CPA) was used to classify cells throughout machine learning and to calculate sensibility of the classification. A sensitivity of 0.94 for dead cells and 0.99 for live cells was calculated using CPA. We did not see any quenching effects of the FITC staining. DAPI signal was reduced in the presence of TB. The results of the present study revealed that TB serves as a dead cell marker in an image cytometric analysis, being able to be combined with other fluorescence markers without loss of fluorescence intensity signal or overlapping emission spectrum. SCANNING 38:857 863, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27353803 TI - Invited Commentary on: Effect of cardiopulmonary bypass on platelet mitochondrial respiration and correlation with aggregation and bleeding: a pilot study. PMID- 27353804 TI - Organ donation depends on trust. PMID- 27353805 TI - Communicating risk about children's heart surgery well. PMID- 27353806 TI - What can public health do for mental health? PMID- 27353807 TI - Alcohol and the Sustainable Development Goals. PMID- 27353808 TI - Use of corticosteroids in tuberculous meningitis. PMID- 27353810 TI - WHO investigates mysterious outbreak in South Sudan. PMID- 27353811 TI - Unaccompanied migrant children at risk across Europe. PMID- 27353812 TI - Gaps in India's health response to violence against women. PMID- 27353813 TI - Tom Potokar--helping burns climb up the international agenda. PMID- 27353814 TI - Association between Guillain-Barre syndrome and Zika virus infection. PMID- 27353815 TI - Association between Guillain-Barre syndrome and Zika virus infection. PMID- 27353816 TI - The PRINTO juvenile dermatomyositis trial. PMID- 27353817 TI - Association between Guillain-Barre syndrome and Zika virus infection - Authors' reply. PMID- 27353818 TI - Ovarian cancer screening: UKCTOCS trial. PMID- 27353819 TI - The PRINTO juvenile dermatomyositis trial - Authors' reply. PMID- 27353820 TI - Ovarian cancer screening: UKCTOCS trial. PMID- 27353821 TI - Ovarian cancer screening: UKCTOCS trial. PMID- 27353822 TI - Ovarian cancer screening: UKCTOCS trial - Authors' reply. PMID- 27353824 TI - Measuring Graph Literacy without a Test: A Brief Subjective Assessment. AB - BACKGROUND: Visual aids tend to help diverse and vulnerable individuals understand risk communications, as long as these individuals have a basic understanding of graphs (i.e., graph literacy). Tests of objective graph literacy (OGL) can effectively identify individuals with limited skills, highlighting vulnerabilities and facilitating custom-tailored risk communication. However, the administration of these tests can be time-consuming and may evoke negative emotional reactions (e.g., anxiety). OBJECTIVES: To evaluate a brief and easy-to use assessment of subjective graph literacy (SGL) (i.e., self-reported ability to process and use graphically presented information) and to estimate the robustness and validity of the SGL scale and compare it with the leading OGL scale in diverse samples from different cultures. PARTICIPANTS: Demographically diverse residents (n = 470) of the United States, young adults (n = 172) and patients (n = 175) from Spain, and surgeons (n = 175) from 48 countries. DESIGN: A focus group and 4 studies for instrument development and initial validation (study 1), reliability and convergent and discriminant validity evaluation (study 2), and predictive validity estimation (studies 3 and 4). MEASURES: Psychometric properties of the scale. RESULTS: In about 1 minute, the SGL scale provides a reliable, robust, and valid assessment of skills and risk communication preferences and evokes fewer negative emotional reactions than the OGL scale. CONCLUSIONS: The SGL scale can be suitable for use in clinical research and may be useful as a communication aid in clinical practice. Theoretical mechanisms involved in SGL, emerging applications, limitations, and open questions are discussed. PMID- 27353825 TI - Quantitative Framework for Retrospective Assessment of Interim Decisions in Clinical Trials. AB - This article presents a quantitative way of modeling the interim decisions of clinical trials. While statistical approaches tend to focus on the epistemic aspects of statistical monitoring rules, often overlooking ethical considerations, ethical approaches tend to neglect the key epistemic dimension. The proposal is a second-order decision-analytic framework. The framework provides means for retrospective assessment of interim decisions based on a clear and consistent set of criteria that combines both ethical and epistemic considerations. The framework is broadly Bayesian and addresses a fundamental question behind many concerns about clinical trials: What does it take for an interim decision (e.g., whether to stop the trial or continue) to be a good decision? Simulations illustrating the modeling of interim decisions counterfactually are provided. PMID- 27353826 TI - Predicting Mean Survival Time from Reported Median Survival Time for Cancer Patients. AB - BACKGROUND: Mean duration of survival following treatment is a prerequisite for cost-effectiveness analyses used for assessing new and costly life-extending therapies for cancer patients. Mean survival time is rarely reported due to censoring imposed by limited follow-up time, whereas the median survival time often is. The empirical relationship between mean and median survival time for cancer patients is not known. AIM: To derive the empirical associations between mean and median survival time across cancer types and to validate this empirical prediction approach and compare it with the standard approach of fitting a Weibull distribution. METHODS: We included all patients in Norway diagnosed from 1960 to 1999 with one of the 13 most common solid tumor cancers until emigration, death, or 31 December 2011, whichever came first. Observed median, restricted mean, and mean survival times were obtained in subcohorts defined by patients' sex, age, cancer type, and time period of diagnosis, which had nearly complete follow-up. Based on theoretical considerations, we fitted a linear relationship between observed means and medians on the log scale. For validation, we estimated mean survival from medians of bootstrap samples with artificially induced censoring and compared with fitting a Weibull distribution. RESULTS: A linear relationship between log-mean survival time and log-median survival time was identified for the 6 cancers with shortest survival plus metastasized breast and prostate cancers. The predicted means of the empirical approach had smaller bias than the standard Weibull approach. CONCLUSION: For cancer diagnoses with poor prognosis, mean survival times could be predicted from corresponding medians. This empirical prediction approach is useful for validation of estimates of mean survival time and sensitivity analyses in settings with aggregated data only. PMID- 27353827 TI - Rotary piston blood pumps: past developments and future potential of a unique pump type. AB - INTRODUCTION: The design of implantable blood pumps is either based on displacement pumps with membranes or rotary pumps. Both pump types have limitations to meet the clinical requirements. Rotary piston blood pumps have the potential to overcome these limitations and to merge the benefits. Compared to membrane pumps, they are smaller and with no need for wear-affected membranes and valves. Compared to rotary pumps, the blood flow is pulsatile instead of a non physiological continuous flow. Furthermore, the risk of flow-induced blood damage and platelet activation may be reduced due to low shear stress to the blood. AREAS COVERED: The past developments of rotary piston blood pumps are summarized and the main problem for long-term application is identified: insufficient seals. A new approach with seal-less drives is proposed and current research on a simplified rotary piston design is presented. Expert commentary: The development of blood pumps focuses mainly on the improvement of rotary pumps. However, medical complications indicate that inherent limitations of this pump type remain and restrict the next substantial step forward in the therapy of heart failure patients. Thus, research on different pump types is reasonable. If the development of reliable drives and bearings succeeds, rotary piston blood pumps become a promising alternative. PMID- 27353829 TI - Physical Activity Moderates the Association Between Pain and PTSD in Treatment Seeking Veterans. AB - OBJECTIVE: Posttraumatic stress disorder (PTSD) and pain are frequently comorbid conditions that can result in bidirectional exacerbations. Initial research suggests physical activity may prevent PTSD symptoms or assist with recovery. Unfortunately, Veterans with PTSD are less likely to engage in physical activity, often citing pain as a primary reason. The current study examines the potential role of physical activity as a moderator of the pain and PTSD relationship. DESIGN: Data were collected from 239 Veterans who were seeking PTSD treatment at a Veterans Affairs (VA) hospital between 2006 and 2013. Veterans completed the Clinician-Administered PTSD Scale (CAPS) to measure PTSD severity and self-report inventories to measure pain and physical activity. Multiple moderated linear regressions were used to examine the influence of physical activity on the relationship between pain and PTSD symptoms. RESULTS: Pain severity and interference were associated with more severe PTSD. Physical activity did not have main effects on PTSD severity. However, it did moderate the relationship between PTSD and pain, such that those who were active, despite high levels of pain severity or pain interference, had fewer PTSD symptoms. CONCLUSIONS: For Veterans seeking treatment for PTSD, physical activity was particularly salient for those reporting high levels of pain severity and intensity. While assessment of pain is recommended with all Veterans, it may also be beneficial to evaluate physical activity in those with prominent pain complaints. Further examination of the role of exercise in integrated care for pain and PTSD is warranted. PMID- 27353832 TI - Relationships Between Living Arrangements and Health Status Among Older Adults in the United States, 2009-2014: Findings From the National Health Interview Survey. AB - Limited research has examined how health varies across living arrangements among older adults. Adults aged 65 years and older were sampled from National Health Interview Survey 2009-2014. Four indicators of health (serious psychological distress, health status, functional limitations, and number of health conditions) were compared across older adults living alone, living with others related/unrelated, living with a spouse/partner (no children), and living with children (no spouse/partner). Regression models showed older adults living with others have the poorest health; they were less likely to report excellent or very good health, had serious psychological distress and limitations in activities of daily living (ADLs), and a greater number of health conditions compared with older adults living with a spouse/partner. However, older women living alone or with children were more likely to report two or more health conditions compared with women living with a spouse/partner, suggesting that in older age, there are gender variations in health across living arrangements. PMID- 27353833 TI - Development of the Older Adult Prescription Drug Assessment Questionnaire for Case Workers. AB - Instruments assessing geriatric case managers' perceptions of prescription abuse are limited. Based on a review of current literature and pilot testing feedback, 22 items were initially assembled to form an older adult Prescription Drug Assessment Questionnaire (PDAQ). Case managers ( N = 161) at an older adult agency located in a Midwestern state were surveyed using the instrument. Data were subjected to exploratory factor analysis using principal axis factoring (PAF) and Promax rotation, and Horn's parallel analysis determined the number of extracted factors. PAF generated a final 11-item three-factor model accounting for 51% of total variance explained: Standard Assessment (Factor 1; four items; infinity = .83), Assessment Belief (Factor 2; three items; infinity = .74), and Problem Scope (Factor 3; four items; infinity = .62). The older adult PDAQ is a brief, data-driven instrument with acceptable psychometric properties for assessing perceptions of prescription drug abuse and misuse assessment and counseling. PMID- 27353834 TI - Smoking Cessation and Changes in Body Mass Index Among Middle Aged and Older Adults. AB - OBJECTIVE: This study contributes to the body of literature examining smoking cessation and body mass index (BMI) for adults aged 50 and older. METHOD: Utilizing the 2004 and 2010 waves of the RAND Health and Retirement Study, this analysis utilized Fixed Effects (FE) regression on a sample of 1,316 adults aged 50 and older. RESULTS: Older adults undergo a small change in BMI after a transition from smoking to nonsmoking during a 6-year period, and this occurs after accounting for individual-level unobserved heterogeneity. More specifically, men experience a BMI gain of 1.24 ( p< .01) and women experience a BMI gain of 1.58 ( p< .01). DISCUSSION: Gerontologists/health professionals can use these results to inform older adults about the potential for a small increase in BMI and, in the process, assuage any apprehensions about excessive weight gain. This insight may encourage a greater number of older adults to cease smoking. PMID- 27353835 TI - Microbiological diagnosis of human papilloma virus infection. AB - Infection with human papillomavirus (HPV) is the leading cause of sexually transmitted infection worldwide. This virus generally causes benign lesions, such as genital warts, but persistent infection may lead to cervical cancer, anal cancer, vaginal cancer, and oropharyngeal cancer, although less frequently. Cervical cancer is a severe disease with a high mortality in some countries. Screening with cytology has been very successful in the last few years, but nowadays there are numerous studies that confirm that cytology should be replaced with the detection of HPV as a first line test in population based screening. There are several commercially available FDA approved tests for screening of cervical cancer. A new strategy, based on individual detection of the high risk genotypes HPV16 and HPV18, present in 70% of cervical cancer biopsies, has been proposed by some experts, and is going to be implemented in most countries in the future. PMID- 27353837 TI - Controlled synthesis and comparison of NiCo2S4/graphene/2D TMD ternary nanocomposites for high-performance supercapacitors. AB - Novel ternary electrode materials based on graphene, NiCo2S4, and transition metal dichalcogenides (TMDs) were designed and fabricated with the intention of exploiting synergistic effects conducive to supercapacitive energy storage. Compared to NiCo2S4-g-MoSe2, the NiCo2S4-g-MoS2 electrode exhibited higher specific capacitance, enhanced rate capability (1002 F g(-1) even at 5 A g(-1), 6.01 F cm(-2) at a current density of 25 mA cm(-2)) and cycling stability (94.8% retention of its original capacity after cycling 4000 times). The mechanism was proposed and this pioneering work will be helpful in making judicious choices of which 2D materials to be selected for supercapacitor applications in the future. PMID- 27353836 TI - DNA signals at isoform promoters. AB - Transcriptional heterogeneity is extensive in the genome, and most genes express variable transcript isoforms. However, whether variable transcript isoforms of one gene are regulated by common promoter elements remain to be elucidated. Here, we investigated whether isoform promoters of one gene have separated DNA signals for transcription and translation initiation. We found that TATA box and nucleosome-disfavored DNA sequences are prevalent in distinct transcript isoform promoters of one gene. These DNA signals are conserved among species. Transcript isoform has a RNA-determined unstructured region around its start site. We found that these DNA/RNA features facilitate isoform transcription and translation. These results suggest a DNA-encoded mechanism by which transcript isoform is generated. PMID- 27353838 TI - Photonic Programmable Tele-Cloning Network. AB - The concept of quantum teleportation allows an unknown quantum states to be broadcasted and processed in a distributed quantum network. The quantum information injected into the network can be diluted to distant multi-copies by quantum cloning and processed by arbitrary quantum logic gates which were programed in advance in the network quantum state. A quantum network combines simultaneously these fundamental quantum functions could lead to new intriguing applications. Here we propose a photonic programmable telecloning network based on a four-photon interferometer. The photonic network serves as quantum gate, quantum cloning and quantum teleportation and features experimental advantage of high brightness by photon recycling. PMID- 27353840 TI - Regulation of the blood-testis barrier. AB - The purpose of this review is to describe the endocrine and local testicular factors that contribute to the regulation of the blood-testis barrier (BTB), using information gained from in vivo and in vitro models of BTB formation during/after puberty, and from the maintenance of BTB function during adulthood. In vivo the BTB, in part comprised of tight junctions between adjacent somatic Sertoli cells, compartmentalizes meiotic spermatocytes and post-meiotic spermatids away from the vasculature, and therefore prevents autoantibody production by the immune system against these immunogenic germ cells. This adluminal compartment also features a unique biochemical milieu required for the completion of germ cell development. During the normal process of spermatogenesis, earlier germ cells continually cross into the adluminal compartment, but the regulatory mechanisms and changes in junctional proteins that allow this translocation step without causing a 'leak' remain poorly understood. Recent data describing the roles of FSH and androgen on the regulation of Sertoli cell tight junctions and tight junction proteins will be discussed, followed by an examination of the role of paracrine factors, including members of the TGFbeta superfamily (TGFbeta3, activin A) and retinoid signalling, as potential mediators of junction assembly and disassembly during the translocation process. PMID- 27353841 TI - Oxazolidinone-containing pseudopeptides: Supramolecular materials, fibers, crystals, and gels. AB - The formation of fibers through self-assembly is of particular interest, as fibrous proteins (such as collagen, keratin, actin, and so on) are involved in intra- and extracellular functions. To understand aggregation phenomena, oligopeptides may be designed and prepared either to mimic or to interfere with these processes. In this article, we will demonstrate that the introduction of the 4-methyl-5-carboxy-oxazolidin-2-one (Oxd) moiety inside a peptide chain favors the formation of fiber-like materials organized either in beta-sheets or in supramolecular helices, provided that it is combined with other factors, like pi-stacking interactions and intermolecular N?H***O?C bonds. The presence of the Oxd moiety is essential for the material formation: when Oxd is replaced with Pro, only liquids or amorphous solids are obtained. Remarkably, some of these molecules are low-molecular-weight gelators, as they induce the formation of both organogel and hydrogels that have been used for several applications. PMID- 27353839 TI - DiPALS: Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis - a randomised controlled trial. AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting in death, usually from respiratory failure, within 2-3 years of symptom onset. Non-invasive ventilation (NIV) is a treatment that when given to patients in respiratory failure leads to improved survival and quality of life. Diaphragm pacing (DP), using the NeuRx/4((r)) diaphragm pacing system (DPS)TM (Synapse Biomedical, Oberlin, OH, USA), is a new technique that may offer additional or alternative benefits to patients with ALS who are in respiratory failure. OBJECTIVE: The Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis (DiPALS) trial evaluated the effect of DP on survival over the study duration in patients with ALS with respiratory failure. DESIGN: The DiPALS trial was a multicentre, parallel-group, open-label, randomised controlled trial incorporating health economic analyses and a qualitative longitudinal substudy. PARTICIPANTS: Eligible participants had a diagnosis of ALS (ALS laboratory supported probable, clinically probable or clinically definite according to the World Federation of Neurology revised El Escorial criteria), had been stabilised on riluzole for 30 days, were aged >= 18 years and were in respiratory failure. We planned to recruit 108 patients from seven UK-based specialist ALS or respiratory centres. Allocation was performed using 1 : 1 non-deterministic minimisation. INTERVENTIONS: Participants were randomised to either standard care (NIV alone) or standard care (NIV) plus DP using the NeuRX/4 DPS. MAIN OUTCOME MEASURES: The primary outcome was overall survival, defined as the time from randomisation to death from any cause. Secondary outcomes were patient quality of life [assessed by European Quality of Life-5 Dimensions, three levels (EQ-5D-3L), Short Form questionnaire-36 items and Sleep Apnoea Quality of Life Index questionnaire]; carer quality of life (EQ-5D-3L and Caregiver Burden Inventory); cost-utility analysis and health-care resource use; tolerability and adverse events. Acceptability and attitudes to DP were assessed in a qualitative substudy. RESULTS: In total, 74 participants were randomised into the trial and analysed, 37 participants to NIV plus pacing and 37 to standard care, before the Data Monitoring and Ethics Committee advised initial suspension of recruitment (December 2013) and subsequent discontinuation of pacing (on safety grounds) in all patients (June 2014). Follow-up assessments continued until the planned end of the study in December 2014. The median survival (interquartile range) was 22.5 months (lower quartile 11.8 months; upper quartile not reached) in the NIV arm and 11.0 months (6.7 to 17.0 months) in the NIV plus pacing arm, with an adjusted hazard ratio of 2.27 (95% confidence interval 1.22 to 4.25; p = 0.01). CONCLUSIONS: Diaphragmatic pacing should not be used as a routine treatment for patients with ALS in respiratory failure. FUTURE WORK: It may be that certain population subgroups benefit from DP. We are unable to explain the mechanism behind the excess mortality in the pacing arm, something the small trial size cannot help address. Future research should investigate the mechanism by which harm or benefit occurs further. TRIAL REGISTRATION: Current Controlled Trials ISRCTN53817913. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 45. See the HTA programme website for further project information. Additional funding was provided by the Motor Neurone Disease Association of England, Wales and Northern Ireland. PMID- 27353842 TI - Can axillary node dissection be safely omitted in the elderly? A retrospective study on axillary management of early breast cancer in older women. AB - INTRODUCTION: Sentinel lymph node biopsy (SLNB) is a minimally invasive technique to stage the axillary lymph node status. The burden of nodal metastasis is of great concern, as the clinical relevance and therapeutic implications of pN1mi and pN0(i+) in the sentinel lymph node (SLN) remain a matter of debate. MATERIALS AND METHODS: We examined the pathological features of 901 patients above the age of 65 presenting with clinical T1-T2 N0M0 breast tumours (<3 cm), detecting tumours related to llary non-sentinel node (NSN) metastases when the SLN was minimally involved. RESULTS: A total of 270 patients underwent complete axillary lymph node dissection (cALND) after their SLNB specimen tested positive for macrometastasis, micrometastasis and isolated tumour cells (ITCs). Seventy-six patients were diagnosed with micrometastatic disease pN1mi (27.5%), whilst ITCs (pN0i+) were detected in seven patients (2.5%). NSNs were found to be involved in two patients (2.6%) with micrometastases at the SLN. No further metastatic disease was detected in NSNs when the SLN contained ITCs. At a median follow-up period of 5.8 years, no axillary recurrence was observed among pN1mi and pN0(i+) patients. Lobular histotype, multicentricity and lymphovascular invasion were found to be associated with NSN involvement. DISCUSSION: The results from our case series are supported by IBCSG 23-01 level 1 evidence, which demonstrated a local recurrence rate of 1% in 'minimally involved not-surgical treated axilla'. CONCLUSIONS: Based on current evidence, we spare well-informed and consenting patients from further axillary surgery when the SLN is minimally involved in early breast cancer within an agreed protocol, whilst scheduling adjuvant treatment based on the patients' primary tumour characteristics. PMID- 27353844 TI - BioEnterics Intragastric Balloon (BIB) versus Spatz Adjustable Balloon System (ABS): Our experience in the elderly. AB - The BioEnterics Intragastric Balloon (BIB) and the Spatz Adjustable Balloon System (ABS) are in fact recommended for weight reduction as a bridge to bariatric surgery. We retrospected studied patients with body mass index (BMI) and age ranges of 37-46 and 70-80 years, respectively, who had undergone BIB from January 2010 to July 2012 and prospected studied patients who had undergone Spatz balloon from July 2012 to August 2014. The aim of this study is to compare BIB and Spatz in terms of weight loss, complications, and maintenance of weight after removal. For both procedures, the median weight loss was 20 +/- 3 kg, median BMI at the end of the therapy was 32 +/- 2, and no severe complication occurred. PMID- 27353843 TI - Liver resection for metastases from colorectal cancer in very elderly patients: New surgical horizons. AB - INTRODUCTION AND AIM: Patients with colorectal cancer (CRC) may develop liver metastases. Surgical resection remains the best treatment of choice for colorectal liver metastases (CRLM) according to resectability criteria, with a long-term survival of 25% up to 41% after 5 years. Advanced age is associated with a higher incidence and co-morbidity, particularly cardiovascular disease, as well as deteriorating physiological reserves. The aim of this study was to analyse the overall and disease-free survival for patients with CRLM according to their chronological age. METHODS: Patients with CRLM were enrolled in the study. Data on gender, age, co-morbidity, metastasis characteristics (number, size and total metastatic volume (TMV)), use of perioperative chemotherapy and operative and post-operative complications were collected. Then, according to recent World Health Organization (WHO) guidelines, the patients were grouped by age. Statistical analysis was performed using the software R (ver. 2.14.1). RESULTS: Hepatic resection was performed in 149 patients (21 patients in the very elderly group, 79 in the elderly group and 49 in the younger group). The three groups were comparable in terms of operative duration, transfusion rate, length of high dependency unit (HDU) stay and post-operative hospital stay. The very elderly group showed a non-significant increase in post-operative morbidity. The 30-day and 60-day/inpatient mortality rates increased with age without any significant statistically difference between the three groups (very elderly group 4.8% and 4.8%; elderly group: 2.5% and 3.8%; and younger group 0% and 2%). At 5 years, the overall survival was 28.6% for very elderly patients (>=75 years), 33.3% for elderly patients (>=65 to <75 years) and 43.5% for younger patients (<=65 years). The 1-, 3- and 5-year disease-free survival was similar across the groups. CONCLUSIONS: Liver resection for CRLM in carefully selected patients above the age of 75 can be performed with acceptable morbidity and mortality rates, similar to those in younger patients. Moreover, the severity of CRLM in elderly patients is proven to be lesser than in younger patients. Thus, we can conclude that advanced chronological age cannot be considered a contraindication to hepatic resection for CRLM. PMID- 27353845 TI - Performance status versus anatomical recovery in metastatic disease: The role of palliative radiation treatment. AB - Metastatic disease is a common complication of the most advanced malignancies. It may compromise the patients' quality of life, often posing a greater risk than the primary disease itself. Currently, several different therapeutic approaches are available to palliate or cure (single metastasis with primary neoplasm under control - radical surgery) secondary disease. In particular, radiation therapy is widely used, as it often leads to full or at least partial functional recovery, depending on the number and location of metastases. The aim of our study was to evaluate whether clinical improvement subsequent to radiation therapy may be related to anatomical recovery of the site of metastasis in cancer patients with metastatic disease. Given the heterogeneity of the diseases considered and the general complex conditions of the patients, a single method could not be used to evaluate the response to radiation treatment and its correlation with the performance status (PS). Thus, depending on the specific disease being assessed, we divided the patients into different groups. Patients in the same group were followed up with the same methods. This correlation was noted in a very high percentage of patients, predominantly in patients with vertebral and brain metastases. Moreover, we investigated the use of magnetic resonance imaging (MRI) diffusion weighted imaging (DWI) in the study of spinal metastases. We propose its use in the local evaluation of vertebral secondary lesions, both in the diagnostic phase and during the assessment of treatment efficacy. PMID- 27353846 TI - Laparoscopic management of non-midline incisional hernia: A multicentric study. AB - BACKGROUND: The laparoscopic repair of non-midline ventral hernia (LNM) has been debated. The aim of this study is to analyze our experience performing the laparoscopic approach to non-midline ventral hernias (NMVHs) in Northwest Italy for 6 years. METHODS: A total of 78 patients who underwent LNM between March 2008 and March 2014 in the selected institutions were analyzed. We retrospectively analyzed the peri- and postoperative data and the recurrence rate of four subgroups of NMVHs: subcostal, suprapubic, lumbar, and epigastric. We also conducted a literature review. RESULTS: No difference was found between the four subgroups in terms of demographic data, defect characteristics, admission data, and complications. Subcostal defects required a shorter operating time. Obesity was found to be a risk factor for recurrence. CONCLUSIONS: In our experience, subcostal defects were easier to perform, with a lower recurrence rate, lesser chronic pain, and faster surgical performance. A more specific prospective randomized trial with a larger sample is awaited. Based on our experience, however, the laparoscopic approach is a safe treatment for NMVHs in specialized centers. PMID- 27353847 TI - Resection of hepatocellular carcinoma in elderly patients and the role of energy balance. AB - INTRODUCTION: Progressive functional impairment with age has a significant impact on perioperative risk management. Chronic liver diseases induce a strong oxidative stress; in the elderly, in particular, impaired elimination of free radicals leads to insufficient DNA repair. The events associated with a weak response to growth factors after hepatectomy leads to a decline in liver regeneration. Hypercholesterolemia is highly prevalent in the elderly, which may alter the coenzyme Q10 (CoQ) levels and in turn the cellular energy balance. This condition is commonly treated with statins. The aim of this study is to investigate the role of preoperative cellular energy balance in predicting hepatocellular carcinoma (HCC) postresection outcomes. MATERIALS AND METHODS: In a 5-year period (2009-2013), elderly patients with hypercholesterolemia, cardiovascular disease, and diabetes mellitus, undergoing HCC resection, were recruited and grouped by age (<75 and >= 75 years old). All patients were previously treated with statins. The risk factors associated with hospital morbidity/mortality and prolonged length of stay (LOS) were evaluated. RESULTS: Forty-five elderly patients were recruited and grouped according to their treatment: Group 1 (n = 23) was treated with statins alone (control group), whereas Group 2 (n = 22) was treated with statins and a CoQ analogue, 3 weeks from the surgery and at least a month later (experimental group). The majority of our patients were treated with atorvastatin [n = 28 (53.84%)] and the minority with simvastatin [n = 17 (32.69%)], 20 mg/day, for at least 3 years before the surgery. Perioperative mortality was observed in one patient of Group 1 (4.3%). Morbidities were noted in 13 patients of Group 1 (56.5%) and four patients of Group 2 (18.2%). The control group showed delayed functional recovery, muscle weakness, increased infection rate, and pleural effusion due to prolonged bed rest (hospital stay 13 days (7-19) vs. 8.5 days (5-12)), compared with the experimental group. The overall survival at 5 years was similar for both groups (n = 10 patients (43%) in Group 1 vs. n = 10 patients (45%) in Group 2). CONCLUSION: In the elderly population, survival is closely linked to postoperative morbidity and mortality. In our study, prolonged LOS was found to be related to delayed bioenergetic recovery. When limited, risk factors such as infections, neutropenia, and red blood cell transfusions could lower LOS and mortality of elderly patients with HCC. Higher age was associated with greater postoperative morbidity and successful hospital stay. PMID- 27353848 TI - Impacts of peritoneal cancer index on the survival outcomes of patients with colorectal peritoneal carcinomatosis. AB - INTRODUCTION: Peritoneal cancer index (PCI) has been suggested to be the most important prognostic factors for the outcomes in colorectal peritoneal carcinomatosis (CRPC). METHODS: This was a retrospective study of prospectively collected data of 168 consecutive patients with CRPC following cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). Patients were divided into five groups according to their PCI. RESULTS: Hospital mortality was 0%. Patients in low PCI groups had a significantly lower major morbidity rate, shorter intensive care unit and high dependency unit stay and higher overall survival (p=0.017, 0.001, 0.046, p<0.001 respectively). CONCLUSION: Combined CRS with PIC can be safely performed to provide encouraging survival benefits for patients with CRPC. Our findings suggest that this approach is particularly beneficial for patients with low volume of disease. Early referral to specialist centre for evaluation is warranted for better survival outcomes. PMID- 27353849 TI - A comparison of the Cook-Swartz Doppler with conventional clinical methods for free flap monitoring: A systematic review and a meta-analysis. AB - INTRODUCTION: Currently there is no consensus on what is the optimal method for monitoring free flaps. Our meta-analysis compared the free flap success and salvage rates of Cook-Swartz Implantable Doppler monitoring with clinical monitoring to gain insight into the relative benefit of these systems. METHODS: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until January 16, 2016. Search terms included free flap surgery, free flap microsurgery and implantable Doppler. Studies were included if they involved the comparison of Cook-Swartz Doppler and clinical assessment for monitoring free flap function. Studies using free flap monitoring as an outcome measure for drug treatment were also excluded. Sensitivity analysis using the leave-one-out approach was used to assay the reliability of the findings. RESULTS: Initial search identified 14 studies, of which five studies were included in the meta-analysis. Cook-Swartz Doppler had significantly better rate of free flap success and salvage than clinical monitoring methods (P values <= 0.006). Data did not markedly changed when each study was removed in turn, showing reliability of the findings. DISCUSSION: The Cook-Swartz Doppler as a monitoring method may result in a higher rate of free flap success and salvaging but also a greater frequency of false positives than conventional methods. Our analysis is limited by designs of included studies and by heterogeneity of clinical monitoring techniques. CONCLUSIONS: More studies are needed to evaluate if Cook-Swartz Doppler can be used alone, or to be better used as an adjunctive technique to complement the clinical method of monitoring. PMID- 27353850 TI - Management of venous ulcers: State of the art. AB - Venous ulceration is a complex and serious problem that affects 1-2% of the global elderly population (>65 years), and its incidence is constantly increasing. The population group with higher risk of development of venous ulceration is the elderly. These lesions have a significant negative impact on patients' quality of life. Our aim was to analyze the state of the art, starting with the medical literature review. The evidence supports that managing chronic wounds with a multidisciplinary wound care team significantly increases wound healing and reduces the severity of wound-associated pain and the required daily wound treatments compared with persons who are not managed by such a team. PMID- 27353851 TI - Could 3D bioprinted tissues offer future hope for microtia treatment? AB - Microtia is a congenital deformity where the pinna is underdeveloped. Contraindications to rib surgery for microtia reconstruction include high-risk surgical status and chest-wall deformities [1-2]. However does stem-cell-based 3D Bioprinting offer revolutionary therapeutic options for patients with such tissue abnormalities. As a technology, 3D-bioprinting is being developed to generate homogeneous tissues by depositing a low viscosity printable cellular-active gel which matures into a tissue [3]. Currently on-going research is developing the process towards producing cartilage tissues for use in reconstructive surgery. This process focuses on using the natural self-organising properties of cells in order to produce a functional tissue which has measurable: mechanical, metabolic and functional properties. PMID- 27353853 TI - Stiff Arteries, Stiff Ventricles: Correlation or Causality in Heart Failure? PMID- 27353852 TI - Association of Aortic Stiffness With Left Ventricular Remodeling and Reduced Left Ventricular Function Measured by Magnetic Resonance Imaging: The Multi-Ethnic Study of Atherosclerosis. AB - BACKGROUND: This study sought to assess cross-sectional associations of aortic stiffness assessed by magnetic resonance imaging with left ventricular (LV) remodeling and myocardial deformation in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS AND RESULTS: Aortic arch pulse wave velocity (PWV) was measured with phase contrast cine magnetic resonance imaging. LV circumferential strain (Ecc), torsion, and early diastolic strain rate were determined by tagged magnetic resonance imaging. Multivariable linear regression models were used to adjust for demographics and cardiovascular risk factors. Of 2093 participants, multivariable linear regression models demonstrated that higher arch PWV was associated with higher LV mass index (B=0.53 per 1 SD increase for log-transformed PWV, P<0.05) and LV mass to volume ratio (B=0.015, P<0.01), impaired LV ejection fraction (LVEF; B=-0.84; P<0.001), Ecc (B=0.55; P<0.001), torsion (B=-0.11; P<0.001), and early diastolic strain rate (B=-0.003; P<0.05). In sex stratified analysis, higher arch PWV was associated with higher MVR (B=0.02; P<0.05), impaired Ecc (B=0.60; P<0.001), and LVEF (B=-0.45; P<0.05), but with maintained torsion in women. Higher PWV was associated with impaired Ecc (B=0.49; P<0.001) and LVEF (B=-1.21; P<0.001), with lower torsion (B=-0.17; P<0.001) in men. CONCLUSIONS: Higher arch PWV is associated with LV remodeling, and reduced LV systolic and diastolic function in a large multiethnic population. Greater aortic arch stiffness is associated with concentric LV remodeling and relatively preserved LVEF with maintained torsion in women, whereas greater aortic arch stiffness is associated with greater LV dysfunction demonstrated as impaired Ecc, torsion, and LVEF, with less concentric LV remodeling in men. PMID- 27353854 TI - MRA_1571 is required for isoleucine biosynthesis and improves Mycobacterium tuberculosis H37Ra survival under stress. AB - Threonine dehydratase is a pyridoxal 5-phosphate dependent enzyme required for isoleucine biosynthesis. Threonine dehydratase (IlvA) participates in conversion of threonine to 2-oxobutanoate and ammonia is released as a by-product. MRA_1571 is annotated to be coding for IlvA in Mycobacterium tuberculosis H37Ra (Mtb-Ra). We developed a recombinant (KD) Mtb-Ra strain by down-regulating IlvA. The growth studies on different carbon sources suggested reduced growth of KD compared to wild-type (WT), also, isoleucine concentration dependent KD growth restoration was observed. The expression profiling of IlvA suggested increased expression of IlvA during oxygen, acid and oxidative stress. In addition, KD showed reduced survival under pH, starvation, nitric oxide and peroxide stresses. KD was more susceptible to antimycobacterial agents such as streptomycin (STR), rifampicin (RIF) and levofloxacin (LVF), while, no such effect was noticeable when exposed to isoniazid. Also, an increase in expression of IlvA was observed when exposed to STR, RIF and LVF. The dye accumulation studies suggested increased permeability of KD to ethidium bromide and Nile Red as compared to WT. TLC and Mass studies confirmed altered lipid profile of KD. In summary down-regulation of IlvA affects Mtb growth, increases its susceptibility to stress and leads to altered cell wall lipid profile. PMID- 27353855 TI - Group sequential monitoring based on the weighted log-rank test statistic with the Fleming-Harrington class of weights in cancer vaccine studies. AB - In recent years, immunological science has evolved, and cancer vaccines are now approved and available for treating existing cancers. Because cancer vaccines require time to elicit an immune response, a delayed treatment effect is expected and is actually observed in drug approval studies. Accordingly, we propose the evaluation of survival endpoints by weighted log-rank tests with the Fleming Harrington class of weights. We consider group sequential monitoring, which allows early efficacy stopping, and determine a semiparametric information fraction for the Fleming-Harrington family of weights, which is necessary for the error spending function. Moreover, we give a flexible survival model in cancer vaccine studies that considers not only the delayed treatment effect but also the long-term survivors. In a Monte Carlo simulation study, we illustrate that when the primary analysis is a weighted log-rank test emphasizing the late differences, the proposed information fraction can be a useful alternative to the surrogate information fraction, which is proportional to the number of events. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27353856 TI - Neuroinflammatory response to experimental stroke is inhibited by eriodictyol. AB - BACKGROUND: Cerebral ischemia is a common disease and one of the most common causes of death and disability worldwide. The lack of glucose and oxygen in neuronal tissue leads to a series of inflammatory events, culminating in neuronal death. Eriodictyol is a flavonoid isolated from the Chinese herb Dracocephalum rupestre that has been proven to have anti-inflammatory properties. HYPOTHESIS/PURPOSE: Thus, the present study was designed to explore whether eriodictyol has neuroprotective effects against the neuronal damage, motor and memory deficits induced by permanent middle cerebral artery occlusion (pMCAO) in mice. STUDY DESIGN: Animals were orally treated with eriodictyol (1, 2 and 4mg/kg) or vehicle (saline) 30min before pMCAO, 2h after, and then once daily for the following five days. METHODS: The parameters studied were neuronal viability, brain infarcted area; sensorimotor deficits; exploratory activity; working and aversive memory; myeloperoxidase (MPO) activity; TNFalpha, iNOS and GFAP immunoreactivity. RESULTS: The treatment with eriodictyol prevented neuronal death, reduced infarct area and improved neurological and memory deficits induced by brain ischemia. The increase of MPO activity and TNF-alpha, iNOS and GFAP expression were also reduced by eriodictyol treatment. CONCLUSION: These findings demonstrate that eriodictyol exhibit promising neuroprotection effects against the permanent focal ischemia cerebral injury in the mice experimental model and the underlying mechanisms might be mediated through inhibition of neuroinflammation. PMID- 27353857 TI - Involvement of glutamatergic N-methyl-d-aspartate receptors in the expression of increased head-dipping behaviors in the hole-board tests of olfactory bulbectomized mice. AB - Olfactory bulbectomized (OB) mice produce agitated anxiety-like behaviors in the hole-board test, which was expressed by an increase in head-dipping counts and a decrease in head-dipping latencies. However, the associated mechanisms remain unclear. In the present study, MK-801 (10, 100MUg/kg), a selective N-methyl-d aspartate (NMDA) receptor antagonist, significantly and dose-dependently suppressed the increased head-dipping behaviors in OB mice, without affecting sham mice. Similar results were obtained with another selective NMDA receptor antagonist D-AP5 treatment in OB mice. On the other hand, muscimol, a selective aminobutyric acid type A (GABAA) receptor agonist produced no effects on these hyperemotional behaviors in OB mice at a dose (100MUg/kg) that produced anxiolytic-like effects in sham mice. Interestingly, glutamine contents and glutamine/glutamate ratios were significantly increased in the amygdala and frontal cortex of OB mice compared to sham mice. Based on these results, we concluded that the glutamatergic NMDA receptors are involved in the expression of increased head-dipping behaviors in the hole-board tests of OB mice. Accordingly, the changes in glutamatergic transmission in frontal cortex and amygdala may play important roles in the expression of these abnormal behaviors in OB mice. PMID- 27353858 TI - Effect of NADH kinase on poly-3-hydroxybutyrate production by recombinant Escherichia coli. AB - The cofactor NADPH participates in a variety of anabolic reactions and its availability is considered to play a critical role in biotransformation processes. NADH kinase (Pos5) from Saccharomyces cerevisiae catalyzes the phosphorylation of NADH to generate NADPH. To investigate the effect of NADH kinase on poly-3-hydroxybutyrate (PHB) production, pos5 was co-expressed with PHB synthetic operon phbCAB in Escherichia coli. The recombinant strain carrying pos5 and phbCAB co-expression plasmid reached 5.96 g/L cell dry weight with 64.1% PHB accumulation in 72 h shake flask cultivation, while the control strain without pos5 yielded 3.93 g/L cell dry weight with 58.5% PHB content. PHB production titer was enhanced from 2.30 g/L to 3.82 g/L. Intracellular cofactor concentration analysis revealed that the ratio of NADP/NAD in pos5 overexpression strain was two times more compared with that of the control without pos5. The results showed that NADH kinase could be employed as an effective metabolic manipulation target to improve PHB synthesis. PMID- 27353859 TI - Heterologous expression of a new manganese-dependent peroxidase gene from Peniophora incarnata KUC8836 and its ability to remove anthracene in Saccharomyces cerevisiae. AB - The white rot fungus Peniophora incarnata KUC8836 has received an attention as the greatest degrader of polycyclic aromatic hydrocarbons (PAHs), which are hazardous xenobiotics and recalcitrant pollutants. To characterize the mechanisms through which MnP degrades PAHs, heterologous expression of manganese-dependent peroxidase (MnP) gene pimp1 was performed in Saccharomyces cerevisiae BY4741 via the pGEM-T Easy vector, resulting in the recombinant plasmid pESC-URA/pimp1 containing the MnP signal peptide. MnP was significantly secreted into the culture medium with galactose as an active protein with higher efficiency (3.58 U mL-1) by transformants than by the wild-type S. cerevisiae. The recombinant MnP protein was shown to have a molecular weight of 44 kDa by western blotting analysis. With regard to enhancing the bioremediation of PAHs in the environment, anthracene was effectively degraded by the MnP encoded by pimp1, with a degradation rate of 6.5% when Tween 80 was added. In addition, the MnP activity of the transformant exhibited the highest efficiency (2.49 U mL-1) during the degradation. These results show that pimp1 might be useful for biodegradation and gene expression technologies at a transcriptional level, and genetic approaches can be improved by incorporating the highly ligninolytic gene pimp1 and the fungus P. incarnata KUC8836. PMID- 27353860 TI - Novel synthetic kojic acid-methimazole derivatives inhibit mushroom tyrosinase and melanogenesis. AB - In this study, two kojic acid-methimazole (2-mercapto-1-methylimidazole, MMI, 1) derivatives, 5-hydroxy-2-{[(1-methyl-1H-imidazol-2-yl)thio]methyl}-4H-pyran-4-one (compound 4) and 5-methoxy-2-{[(1-methyl-1H-imidazol-2-yl)thio]methyl}-4H-pyran-4 one (compound 5), were synthesized to examine their inhibitory kinetics on mushroom tyrosinase. Compound 4 exhibited a potent inhibitory effect on monophenolase activity in a dose-dependent manner, with an IC50 value of 0.03 mM. On diphenolase activity, compound 4 exhibited a less inhibitory effect (IC50 = 1.29 mM) but was stronger than kojic acid (IC50 = 1.80 mM). Kinetic analysis indicated that compound 4 was both as a noncompetitive monophenolase and diphenolase inhibitor. By contrast, compound 5 exhibited no inhibitory effects on mushroom tyrosinase activity. The IC50 value of compound 4 for the 2,2-diphenyl-1 picrylhydrazyl (DPPH) radical scavenging activity was 4.09 mM, being much higher than the IC50 of compound 4 for inhibiting the tyrosinase activity. The results indicated that the antioxidant activity of compound 4 may be partly related to the potent inhibitory effect on mushroom tyrosinase. Compound 4 also exerted a potent inhibitory effect on intracellular melanin formation in B16/F10 murine melanoma cells, and caused no cytotoxicity. Furthermore, compound 4 induced no adverse effects on the Hen's egg test-chorioallantoic membrane (HET-CAM). PMID- 27353861 TI - Mantle Subduction and Uplift of Intracontinental Mountains: A Case Study from the Chinese Tianshan Mountains within Eurasia. AB - The driving mechanism that is responsible for the uplift of intracontinental mountains has puzzled geologists for decades. This study addresses this issue by using receiver function images across the Chinese Tianshan Mountains and available data from both deep seismic profiles and surface structural deformation. The near-surface structural deformation shows that the Tianshan crust experienced strong shortening during the Cenozoic. The receiver function image across the Tianshan Mountains reveals that the lithosphere of the Junggar Basin to the north became uncoupled along the Moho, and the mantle below the Moho subducted southwards beneath the northern part of the Tianshan Mountains, thereby thickening the overlying crust. Similar deep structures, however, are not observed under the Tarim Basin and the adjacent southern Tianshan Mountains. This difference in the deep structures correlates with geomorphological features in the region. Thus, a new model of mantle subduction, herein termed M-type subduction, is proposed for the mountain-building processes in intracontinental compressional settings. The available geomorphological, geological and seismic data in the literatures show that this model is probably suitable for other high, linear mountains within the continent. PMID- 27353862 TI - Triggers and nursing influences on delirium in intensive care units. AB - Among care providers, nurses have the most influence on the occurrence of delirium in patients. To identify and investigate the risk factors associated with delirium and analyse the nurse's influence on delirium, a secondary data analysis approach was used with clinical data from the electronic medical record and health care provider data from the management information systems of a university hospital. Data of 3284 patients (delirium = 688, non-delirium = 2596) hospitalized in the medical and surgical intensive care units containing 2178 variables were analysed. Donabedian's structure-process-outcome model was applied to categorize the factors for multilevel hierarchical logistic regression analysis. Sixteen factors (10 patient factors, 1 provider factor, 1 environmental factor, 2 nursing intervention factors and 2 medical intervention factors) were identified as significant in the final model. Longer intensive care unit experience of nurses did not decrease the risk of delirium. Greater number of nursing intervention needs and greater use of restraints were associated with an increased risk of delirium. The duration of nursing career did not affect the reduction of the risk of delirium. Nurses should therefore endeavour to acquire nursing experience specific for delirium care and attend training courses for delirium management. PMID- 27353864 TI - Big bad wolf or man's best friend? Unmasking a false wolf aggression on humans. AB - The return of the wolf in its historical range is raising social conflicts with local communities for the perceived potential threat to people safety. In this study we applied molecular methods to solve an unusual case of wolf attack towards a man in the Northern Italian Apennines. We analysed seven biological samples, collected from the clothes of the injured man, using mtDNA sequences, the Amelogenin gene, 39 unlinked autosomal and four Y-linked microsatellites. Results indicated that the aggression was conducted by a male dog and not by a wolf nor a wolf x dog hybrid. Our findings were later confirmed by the victim, who confessed he had been attacked by the guard dog of a neighbour. The genetic profile of the owned dog perfectly matched with that identified from the samples previously collected. Our results prove once again that the wolf does not currently represent a risk for human safety in developed countries, whereas most animal aggressions are carried out by its domestic relative, the dog. PMID- 27353865 TI - Narrow-band UVB phototherapy and psoralen-ultraviolet A photochemotherapy in the treatment of cutaneous mastocytosis: a study in 20 patients. AB - BACKGROUND: In mastocytosis, the skin is almost invariably involved, and cutaneous symptoms deeply affect patients' quality of life. METHODS: A retrospective observational analysis of patients affected by cutaneous mastocytosis (CM) and indolent systemic mastocytosis (ISM) treated with phototherapy/photochemotherapy (PUVA or NB-UVB) has been conducted. For each patient, total numbers of PUVA or NB-UVB exposures, the cumulative UV dose (J/cm2 ), serum tryptase profile, and pruritus, before and after treatment, according to the visual analogue scale (VAS) were considered. Skin lesions of each patient were assessed, before and after treatment, according to a cutaneous scale score. RESULTS: Twenty patients affected by CM and ISM were studied; in particular, 10 patients received NB-UVB therapy, and other 10 patients received PUVA. A statistically significant mean reduction of pruritus in both groups (P < 0.01) was observed. The number of treatments necessary to obtain symptom relief was significantly lower in the PUVA group, but the mean exposure dose was significantly higher, if compared to the NB-UVB group. Serum tryptase levels showed a downward trend. The cutaneous score improved in both groups. LIMITATIONS: This study was a retrospective study with a small sample size and without a control group. CONCLUSION: This work provides evidence that both NB-UVB and PUVA represent a safe and useful second-line therapy of the cutaneous symptoms in mastocytosis. PMID- 27353863 TI - SARI inhibits angiogenesis and tumour growth of human colon cancer through directly targeting ceruloplasmin. AB - SARI, also called as BATF2, belongs to the BATF family and has been implicated in cancer cell growth inhibition. However, the role and mechanism of SARI in tumour angiogenesis are elusive. Here we demonstrate that SARI deficiency facilitates AOM/DSS-induced colonic tumorigenesis in mice. We show that SARI is a novel inhibitor of colon tumour growth and angiogenesis in mice. Antibody array and HUVEC-related assays indicate that VEGF has an essential role in SARI-controlled inhibition of angiogenesis. Furthermore, Co-IP/PAGE/mass spectrometry indicates that SARI directly targets ceruloplasmin (Cp), and induces protease degradation of Cp, thereby inhibiting the activity of the HIF-1alpha/VEGF axis. Tissue microarray results indicate that SARI expression inversely correlates with poor clinical outcomes in colon cancer patients. Collectively, our results indicate that SARI is a potential target for therapy by inhibiting angiogenesis through the reduction of VEGF expression and is a prognostic indicator for patients with colon cancer. PMID- 27353866 TI - Contributions to the phytotherapies of digestive disorders: Traditional knowledge and cultural drivers of Manoor Valley, Northern Pakistan. AB - ETHNO PHARMACOLOGICAL RELEVANCE: Ethno medicinal traditional knowledge regarding the uses of indigenous medicinal plants used for various human digestive disorders are mostly known to the elder community members. As the young generation is not much aware about such vital traditional medicinal practice because they rely on elders. AIM OF STUDY: To document, accumulate and widely disseminate the massive indigenous knowledge of century's practiced therapeutic uses of medicinal plants by the local people living in this remote area. MATERIALS AND METHODS: A total of 63 local inhabitants (39 males and 24 females) were interviewed through a structured questionnaire. The data obtained were quantitatively analyzed through the use value (UVi), fidelity level index (FL%) and relative frequency citations (RFCs), consensus index (CI%) and informant consensus factor (FIC). For novel uses all the plants were checked with previously published articles on same disease by analyzing through Jaccard index (JI) and Sorensen's similarity index (QS). Plants specimen were preserved, mounted and labeled on the herbarium sheets, cataloged and deposited with voucher numbers in Hazara University Herbarium, Mansehra, Pakistan (HUP). RESULTS: 44 plant species belonging to 44 genera and 28 families were documented in the current study. These medicinal plant species were used commonly as an ethno medicine against 26 various digestive disorders out of which most frequently occurred are; stomach ache, diarrhea, indigestion, constipation and inflammation etc. Herbaceous plant species were the dominant among plants studied which were 64% of the total plants, followed by trees (20%) and shrubs (16%). Lamiaceae was the leading family among collected medicinal plant species (13.6%). Maximum medicinal plant species were used for treatment of stomach ache (11.7%), diarrhea and indigestion (10.9% each). Most widely used parts were leaves (41% citations), fruit and whole plant (12% citations each) for medication of various digestive problems by the traditional drivers. Dominated medicinal plants with most use values were Ficus carica having (UVi=0.90) and Trifolium repens (UVi=0.84). Based on the RFC values, the most cited medicinal plant species by the traditional drivers were Ficus carica (0.43) and Berberis lycium (0.41), while most respondents percentage was noticed for same plant species calculated through consensus index (CI%=42.9% and 41.3%) respectively. The medicinal plant species with highest fidelity level was of Grewia optiva, Juglans regia and Sorbaria tomentosa each cited 100% for anthelmintic, easy digestion and Diarrhea respectively. Due to representation by only single medicinal plant taxa (Nt=1), the digestive diseases viz. cholera, colon cancer, emetic, internal injuries, kill microorganisms, Soothing, tumor and urine suppression had maximum FIC value. The analytical result reveals that 57% of medicinal plant species were reported for the first time regarding their uses. new medicinal uses of Anaphalis contorta, Caltha palustris, Pinus wallichiana, Plantago himalaica were recorded for the first time from Pakistan and Aralia cachemirica, Bupleurum longicaule, Pleurospermum stellatum, Potentilla argentea and Juglans regia across the globe for currently reported medicinal uses. Besides this, all the mentioned plant species were reported for the first time for digestive disorders from Manoor Valley as no single study up-till now has been conducted ethno medicinally. CONCLUSION: The present study revealed the importance to document and launch list of all the possible plants that are used in traditional medicinal practices against digestive disorders in the unexplored study area and to show the important medicinal plants for future biological, phytochemical and pharmacological experimentation regarding digestive problems. PMID- 27353867 TI - alpha-Cyperone of Cyperus rotundus is an effective candidate for reduction of inflammation by destabilization of microtubule fibers in brain. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Cyperus rotundus L. (Cyperaceae), commonly known as purple nutsedge or nut grass is one of the most invasive and endemic weeds in tropical, subtropical and temperate regions. This plant has been extensively used in traditional medicine for anti-arthritic, antidiarrheal and antiplatelet properties as well as treatment for several CNS disorders such as epilepsy, depression and inflammatory disorders. Inflammation is evidently occurring in pathologically susceptible regions of the Alzheimer's disease (AD) brain as well as other disorders. Many cellular processes are responsible in chronic inflammation. Microtubule-based inflammatory cell chemotaxis is a well-recognized process that influences production of cytokines and phagocytosis. The effect of alpha-Cyperone, one of main ingredients of Cyperus rotundus on microtubule assembly and dynamics has not been examined and is the purpose of this investigation. MATERIALS AND METHODS: Microtubules and tubulin were extracted in order to explore their interaction with alpha-Cyperone by utilization of turbidimetric examinations, intrinsic fluorescence and circular dichroism spectroscopy (CD) studies. The molecular docking analysis was executed in order to facilitate a more detail and stronger evidence of this interaction. The BINding ANAlyzer (BINANA) algorithm was used to evaluate and further substantiate the binding site of alpha-Cyperone. RESULTS: It was demonstrated that alpha Cyperone had a pronounced influence on the tubulin structure, decreased polymerization rate and reduced concentration of polymerized tubulin in vitro. The CD deconvolution analysis concluded that significant conformational changes occurred, demonstrated by a drastic increase in content of beta-strands upon binding of alpha-Cyperone. The fluorescence spectroscopy revealed that a static type of quenching mechanism is responsible for binding of alpha-Cyperone to tubulin. Upon characterization of various biophysical parameters, it was further deduced that ligand binding was spontaneous and a single site of binding was confirmed. Transmission electron microscopy revealed that upon binding of alpha Cyperone to microtubule the number and complexity of fibers were noticeably decreased. The computational analysis of docking suggested that alpha-Cyperone binds preferably to beta-tubulin at a distinct location with close proximity to the GTP binding and hydrolysis site. The ligand interaction with beta-tubulin is mostly hydrophobic and occurs at amino acid residues that are exclusively on random coil. The BINANA 1.2.0 algorithm which counts and tallies close molecular interaction by performing defined set of simulations revealed that amino acid residues Arg 48 and Val 62 have registered the highest scores and are possibly crucial in ligand-protein interaction. CONCLUSION: alpha-Cyperone binds and interacts with tubulin and is capable of distinctly destabilizing microtubule polymerization. The effect of this interaction could result in reduction of inflammation which would be highly beneficial for treatment of inflammatory diseases such as AD. PMID- 27353868 TI - Phytochemistry and pharmacology of the genus Drypetes: A review. AB - AIMS: Traditional medicinal use of species of the genus Drypetes is widespread in the tropical regions. The aim of this review is to systematically appraise the literature available to date on phytochemistry, ethnopharmacology, toxicology and bioactivity (in vitro and in vivo) of crude extracts and purified compounds. ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the genus Drypetes (Putranjivaceae) are used in the Subsaharan African and Asian traditional medicines to treat a multitude of disorders, like dysentery, gonorrhoea, malaria, rheumatism, sinusitis, tumours, as well as for the treatment of wounds, headache, urethral problems, fever in young children, typhoid and several other ailments. Some Drypetes species are used to protect food against pests, as an aphrodisiac, a stimulant/depressant, a rodenticide and a fish poison, against insect bites, to induce conception and for general healing. This review deals with updated information on the ethnobotany, phytochemistry, and biological activities of ethnomedicinally important Drypetes species, in order to provide an input for the future research opportunities. METHODS: An extensive review of the literature available in various recognized databases e.g., Google Scholar, PubMed, Science Direct, SciFinder, Web of Science, www.theplantlist.org and www.gbif.org, as well as the Herbier National du Cameroun (Yaounde) and Botanic Gardens of Limbe databases on the uses and bioactivity of various species of the Drypetes was undertaken. RESULTS: The literature provided information on ethnopharmacological uses of the Subsaharan African and Asian species of the genus Drypetes, e.g., Drypetes aubrevillii, D. capillipes, D. chevalieri, D. gerrardii, D. gossweileri, D. ivorensis, D. klainei, D. natalensis, D. pellegrini (all endemic to Africa) and D. roxburghii (Asian species), for the treatment of multiple disorders. From a total of 19 species, more than 140 compounds including diterpenes, sesquiterpenes, triterpenes (friedelane, oleanane, lupane and hopane-type), flavonoids, lignans, phenylpropanoids and steroids, as well as some thiocyanates, were isolated. Several crude extracts of these plants, and isolated compounds displayed significant analgesic, anthelmintic, antidiabetic, anti-emetic anti inflammatory, antioxidant, antiparasitic, central nervous system depressant, cytotoxic, and insecticidal activities both in vitro and in vivo. Some toxicities associated with the stem, bark, seed and leaf extracts of D. roxburghii, and the flavonoid, amentoflavone, isolated from the stem extract of D. littoralis as well as D. gerrardii, were confirmed in the animal models and in the rat skeletal myoblast cells assays. As a consequence, traditional medicine from this genus should in future be applied with care. CONCLUSIONS: Plants of this genus have offered bioactive samples, both from crude extracts and pure compounds, partly validating their effectivity in traditional medicine. However, most of the available scientific literatures lacks information on relevant doses, duration of the treatment, storage conditions and positive controls for examining bioefficacy of extract and its active compounds. Additional toxicological studies on the species used in local pharmacopeia are urgently needed to guarantee safe application due to high toxicity of some crude extracts. Interestingly, this review also reports 10 pimarane dinorditerpenoids structures with the aromatic ring C, isolated from the species collected in Asia Drypetes littoralis (Taiwan), D. perreticulata (China), and in Africa D. gerrardii (Kenya), D. gossweileri (Cameroon). These compounds might turn out to be good candidates for chemotaxonomic markers of the genus. PMID- 27353869 TI - Retracted: Detection of Abnormal Hemoglobin Variants by HPLC Method: Common Problems with Suggested Solutions. AB - [This retracts the article DOI: 10.1155/2014/257805.]. PMID- 27353870 TI - Polymer-free nanofibers from vanillin/cyclodextrin inclusion complexes: high thermal stability, enhanced solubility and antioxidant property. AB - Vanillin/cyclodextrin inclusion complex nanofibers (vanillin/CD-IC NFs) were successfully obtained from three modified CD types (HPbetaCD, HPgammaCD and MbetaCD) in three different solvent systems (water, DMF and DMAc) via an electrospinning technique without using a carrier polymeric matrix. Vanillin/CD IC NFs with uniform and bead-free fiber morphology were successfully produced and their free-standing nanofibrous webs were obtained. The polymer-free CD/vanillin IC-NFs allow us to accomplish a much higher vanillin loading (~12%, w/w) when compared to electrospun polymeric nanofibers containing CD/vanillin-IC (~5%, w/w). Vanillin has a volatile nature yet, after electrospinning, a significant amount of vanillin was preserved due to complex formation depending on the CD types. Maximum preservation of vanillin was observed for vanillin/MbetaCD-IC NFs which is up to ~85% w/w, besides, a considerable amount of vanillin (~75% w/w) was also preserved for vanillin/HPbetaCD-IC NFs and vanillin/HPgammaCD-IC NFs. Phase solubility studies suggested a 1 : 1 molar complexation tendency between guest vanillin and host CD molecules. Molecular modelling studies and experimental findings revealed that vanillin : CD complexation was strongest for MbetaCD when compared to HPbetaCD and HPgammaCD in vanillin/CD-IC NFs. For vanillin/CD-IC NFs, water solubility and the antioxidant property of vanillin was improved significantly owing to inclusion complexation. In brief, polymer-free vanillin/CD-IC NFs are capable of incorporating a much higher loading of vanillin and effectively preserve volatile vanillin. Hence, encapsulation of volatile active agents such as flavor, fragrance and essential oils in electrospun polymer free CD-IC NFs may have potential for food related applications by integrating the particularly large surface area of NFs with the non-toxic nature of CD and inclusion complexation benefits, such as high temperature stability, improved water solubility and an enhanced antioxidant property, etc. PMID- 27353871 TI - Authors' reply to Thomas and colleagues. PMID- 27353872 TI - Smothering in UK free-range flocks. Part 2: investigating correlations between disease, housing and management practices. AB - Smothering, when birds group together in a way that results in death from suffocation, is a welfare and economic concern for the egg industry. This questionnaire-based study explored correlations between disease, housing, management practices and smothering on free-range farms. A binomial logistic regression approach was used to test whether question responses predicted occurrence of nest box smothers (NBS) and panic and recurring smothers (PSRS) on farms. Breed (P=0.008) and nest box manufacturer (P=0.014) predicted NBS. Breed and nest box design have been previously reported to affect nesting behaviour. The affect of nest box manufacturer found in this study may illustrate the effect of nest box design features or house layouts. Nest box manufacturer (P=0.009), feeding oyster grit or grain on the litter (P<0.001) and range use on a sunny day (P<0.001) also predicted PSRS. Implementing some management practices to encourage desirable behaviours (eg ranging) may contribute to smothering, whereas some management practices such as those aimed at occupying birds may be beneficial, illustrating the delicate balance of factors involved in free-range egg production. It is hoped that these results will stimulate further work exploring the suitability of housing design and management of laying hens in light of smothering. PMID- 27353873 TI - Assessment of unnecessary suffering in animals by veterinary experts. AB - Veterinary surgeons are often asked to provide reports to courts describing factual observations and their expert opinion on the presence or absence of unnecessary suffering in animals. This study reviewed 42 expert witness reports in order to describe the approach taken to the assessment of unnecessary suffering. While most reports suitably described factual observations, there was significant variation in the opinions on suffering and the actions of the owner. Severity and duration of potential suffering was commented upon in 26 and 29 reports, respectively. Experts used terms associated with negative mental states and physical states in 28 and 27 reports, respectively. The necessity of suffering was commented upon in 27 reports, with minimal commentary on the actions of the owner. External references supporting the opinion of the expert were only provided in 13 reports. There was evidence of disputes between experts concerning the definition of suffering, the significance of clinical findings and the relevance of different assessment methods. It is suggested that expert witness reports should include a systematic consideration of the animal's mental and physical states, severity of harm, duration of harm and a commentary on the necessity of suffering as defined by legislation. PMID- 27353874 TI - Questionnaire regarding skin disorders in pet and smallholder pigs. PMID- 27353875 TI - Cumulative incidence and risk factors for limber tail in the Dogslife labrador retriever cohort. AB - Limber tail is a condition that typically affects larger working breeds causing tail limpness and pain, resolving without veterinary intervention. It is poorly understood and the disease burden has not been well characterised. Data collected from owners of the Dogslife cohort of Labrador Retrievers have been used to describe incidents and a case-control study was undertaken to elucidate risk factors with 38 cases and 86 controls. The cumulative incidence of unexplained tail limpness was 9.7 per cent. Swimming is not a necessary precursor for limber tail, but it is a risk factor (OR=4.7) and working dogs were more susceptible than non-working dogs (OR=5.1). Higher latitudes were shown to be a risk factor for developing the condition and the case dogs were more related to each other than might be expected by chance. This suggests that dogs may have an underlying genetic predisposition to developing the condition. This study is the first, large-scale investigation of limber tail and the findings reveal an unexpectedly high illness burden. Anecdotally, accepted risk factors have been confirmed and the extent of their impact has been quantified. Identifying latitude and a potential underlying genetic predisposition suggests avenues for future work on this painful and distressing condition. PMID- 27353876 TI - Moxie matters: associations of future orientation with active life expectancy. AB - OBJECTIVE: Being oriented toward the future has been associated with better future health. We studied associations of future orientation with life expectancy and the percentage of life with disability. METHOD: We used the Panel Study of Income Dynamics (n = 5249). Participants' average age in 1968 was 33.0. Six questions repeatedly measured future orientation, 1968-1976. Seven waves (1999 2011, 33,331 person-years) measured disability in activities of daily living for the same individuals, whose average age in 1999 was 64.0. We estimated monthly probabilities of disability and death with multinomial logistic Markov models adjusted for age, sex, race/ethnicity, childhood health, and education. Using the probabilities, we created large populations with microsimulation, measuring disability in each month for each individual, age 55 through death. RESULTS: Life expectancy from age 55 for white men with high future orientation was age 77.6 (95% confidence interval 75.5-79.0), 6.9% (4.9-7.2) of those years with disability; results with low future orientation were 73.6 (72.2-75.4) and 9.6% (7.7-10.7). Comparable results for African American men were 74.8 (72.9-75.3), 8.1 (5.6-9.3), 71.0 (69.6-72.8), and 11.3 (9.1-11.7). For women, there were no significant differences associated with levels of future orientation for life expectancy. For white women with high future orientation 9.1% of remaining life from age 55 was disabled (6.3-9.9), compared to 12.4% (10.2-13.2) with low future orientation. Disability results for African American women were similar but statistically significant only at age 80 and over. CONCLUSION: High future orientation during early to middle adult ages may be associated with better health in older age. PMID- 27353877 TI - Modified Rhytidectomy that Produces a More Natural Look: Experience with 110 Cases. AB - BACKGROUND: Recognition of the effects of aging on the ear and the mechanisms leading to ear deformity associated with facelift procedures aid in achieving improved aesthetic results. In 2009, the author developed a novel rhytidectomy technique to provide more natural-looking results than those achieved through other facelift procedures, which often result in facial and ear distortion/deformity. This technique is designed to optimize aesthetic outcomes by employing incisions hidden within the ear, autologous fat transfer to restore normally lost facial volume, and absorbable bidirectional sutures, all of which allow less skin removal and shorter, more concealable scars within the inside perimeter of the ear, and thus less-distorted facial contours. In this retrospective study, the author added one important modification to this previously described approach for preventing ear deformity. OBJECTIVES: The author will show that this modified rhytidectomy technique has many benefits over a traditional rhytidectomy, and it results in a natural-looking facelift. METHODS: The author modified the original technique to secure the ears in a way that prevents inferior drifting. The modified technique involves the placement of two parallel strands of 3-0 Monocryl sutures under the scalp and over the skull and running from one side of the head to the other side using a 6-inch blunt needle. The absorbable strands are passed from the inferior part of each earlobe one in front of the ear and the other in back of the ear. The strands are tied with knots under moderate tension under each earlobe, securing the ear back in the anatomical preoperative position. This secures the bottom of the ears and prevents caudal drifting. DISCUSSION: The use of 360 degrees round-block, inside the-ear incisions is advantageous. These incisions have much less lymphatic derangement of the skin, because the overall cut is shorter and the skin is not cut as extensively as in other methods that use longer incisions to get rid of more excess skin in facelifts. RESULTS: This modified rhytidectomy technique has many benefits over a traditional rhytidectomy: the incisions are hidden inside the ears, so there are almost no visible external incisions, and there is no deformity of the ears and earlobes, because the ears do not drift downward. The ear canal is not distorted, there is no hairline distortion, and most importantly, it results in a natural-looking facelift without the commonly seen deformity of any noticeable pulling. CONCLUSIONS: This modified approach to rhytidectomy achieves natural looking, aesthetically pleasing results. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 27353883 TI - Predictors of early discharge after open gynecological surgery in the setting of an enhanced recovery after surgery protocol. AB - AIM: Enhanced recovery after surgery (ERAS) protocols have been proven to decrease length of hospital stay without increasing readmission rates or complications. However, patient and operative characteristics that improve the chance of successful early hospital discharge are unknown. The aim of this study was to determine the characteristics of patients undergoing open gynecological surgery in an ERAS protocol who could be discharged home by postoperative day 3. METHODS: A retrospective review was performed on patients undergoing laparotomy by a single surgeon and managed by an ERAS protocol between January 2008 and April 2013. Data collection on patient characteristics, hospitalization and post discharge details was performed prospectively. Patients successfully discharged home on or by day 3 (early discharge) were compared to patients who had a longer admission (late discharge). RESULTS: During the study period, 454 consecutive patients were identified and included in the study. No patients were excluded. A total of 335 patients (73.8%) were successfully discharged home within 3 days. After adjusting for age and Eastern Cooperative Oncology Group performance score, patients with early discharge were significantly less likely to have a malignancy (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.36-0.97; P = 0.038), intensive care unit admission (OR, 0.59; 95%CI, 0.36-0.97; P = 0.046), vertical midline incision (OR, 0.28; 95%CI, 0.07-0.82), complications (OR, 0.21; 95%CI, 0.09-0.49; P = 0.0003), or FIGO Stage III or IV disease (OR, 0.39; 95%CI, 0.23 0.67; P = 0.001). Prior abdominal surgery, body mass index > 25 and lymph node dissection did not significantly influence length of hospital stay. CONCLUSION: Malignancy, advanced-stage disease, intensive care unit admission, vertical midline incision and perioperative complications are significantly associated with longer hospital stay in patients managed by an ERAS protocol. PMID- 27353884 TI - 2.5-Year-Olds Express Suspense When Others Approach Reality With False Expectations. AB - The study investigated if 2.5-year-olds are susceptible to suspense and express tension when others' false expectations are about to be disappointed. In two experiments (N = 32 each), children showed more tension when a protagonist approached a box with a false belief about its content than when she was ignorant. In Experiment 2, children also expressed more tension when the protagonist's belief was false than when it was true. The findings reveal that toddlers affectively anticipate the "rude awakening" of an agent who is about to discover unexpected reality. They thus not only understand false beliefs per se but also grasp the affective implications of being mistaken. The results are discussed with recourse to current theories about early understanding of false beliefs. PMID- 27353885 TI - Parametrization of halogen bonds in the CHARMM general force field: Improved treatment of ligand-protein interactions. AB - A halogen bond is a highly directional, non-covalent interaction between a halogen atom and another electronegative atom. It arises due to the formation of a small region of positive electrostatic potential opposite the covalent bond to the halogen, called the 'sigma hole.' Empirical force fields in which the electrostatic interactions are represented by atom-centered point charges cannot capture this effect because halogen atoms usually carry a negative charge and therefore interact unfavorably with other electronegative atoms. A strategy to overcome this problem is to attach a positively charged virtual particle to the halogen. In this work, we extend the additive CHARMM General Force Field (CGenFF) to include such interactions in model systems of phenyl-X, with X being Cl, Br or I including di- and trihalogenated species. The charges, Lennard-Jones parameters, and halogen-virtual particle distances were optimized to reproduce the orientation dependence of quantum mechanical interaction energies with water, acetone, and N-methylacetamide as well as experimental pure liquid properties and relative hydration free energies with respect to benzene. The resulting parameters were validated in molecular dynamics simulations on small-molecule crystals and on solvated protein-ligand complexes containing halogenated compounds. The inclusion of positive virtual sites leads to better agreement across experimental observables, including preservation of ligand binding poses as a direct result of the improved representation of halogen bonding. PMID- 27353886 TI - Small molecule non-peptide inhibitors of botulinum neurotoxin serotype E: Structure-activity relationship and a pharmacophore model. AB - Botulinum neurotoxins (BoNTs) are the most poisonous biological substance known to humans. They cause flaccid paralysis by blocking the release of acetylcholine at the neuromuscular junction. Here, we report a number of small molecule non peptide inhibitors of BoNT serotype E. The structure-activity relationship and a pharmacophore model are presented. Although non-peptidic in nature, these inhibitors mimic key features of the uncleavable substrate peptide Arg-Ile-Met Glu (RIME) of the SNAP-25 protein. Among the compounds tested, most of the potent inhibitors bear a zinc-chelating moiety connected to a hydrophobic and aromatic moiety through a carboxyl or amide linker. All of them show low micromolar IC50 values. PMID- 27353887 TI - Synthesis and anticancer activity of novel 4-morpholino-7,8-dihydro-5H thiopyrano[4,3-d]pyrimidine derivatives bearing chromone moiety. AB - Herein, we designed and synthesized of a novel series of 7,8-dihydro-5H thiopyrano[4,3-d]pyrimidine derivatives bearing chromone moiety (10a-j, 13a-j). All the compounds were evaluated for the IC50 values against five cancer cell lines (A549, PC-3, MCF-7, Hela and HepG2). Seven of the target compounds exhibited moderate to excellent cytotoxicity. For these compounds, we tested their inhibitory activities against mTOR kinase, and four of them were tested their inhibitory activities against PI3Kalpha kinase in further. The results indicated that the optimized compound 10j showed excellent inhibitory activity and cytotoxicity against mTOR kinase, PI3Kalpha kinase and five cancer cell lines with IC50 values of 1.1MUM, 0.92MUM and 8.77-14.3MUM. Structure-activity relationships (SARs) and docking studies indicated that the thiopyrano[4,3 d]pyrimidine scaffolds exerted little effect on antitumor activities of target compounds. Substitutions of chromone moiety at C-6 position with carboxyl were benefit to the antitumor activities. PMID- 27353888 TI - Design, synthesis and evaluation of novel indandione derivatives as multifunctional agents with cholinesterase inhibition, anti-beta-amyloid aggregation, antioxidant and neuroprotection properties against Alzheimer's disease. AB - A series of novel 2-(4-(4-substituted piperazin-1-yl)benzylidene)-1H-indene 1,3(2H)-diones were designed, synthesized and appraised as multifunctional anti Alzheimer agents. In vitro studies of compounds 27-38 showed that these compounds exhibit moderate to excellent AChE, BuChE and Abeta aggregation inhibitory activity. Notably, compounds 34 and 38 appeared as most active multifunctional agents in the entire series and exhibited excellent inhibition against AChE (IC50=0.048MUM: 34; 0.036MUM: 38), Abeta aggregation (max% inhibition 82.2%, IC50=9.2MUM: 34; max% inhibition 80.9%, IC50=10.11MUM: 38) and displayed significant antioxidant potential in ORAC-FL assay. Both compounds also successfully diminished H2O2 induced oxidative stress in SH-SY5Y cells. Fascinatingly, compounds 34 and 38 showed admirable neuroprotective effects against H2O2 and Abeta induced toxicity in SH-SY5Y cells. Additionally, both derivatives showed no considerable toxicity in neuronal cell viability assay and represented drug likeness properties in the primarily pharmacokinetics study. All these results together, propelled out that compounds 34 and 38 might serve as promising multi-functional lead candidates for treatment of AD in the future. PMID- 27353889 TI - The design strategy of selective PTP1B inhibitors over TCPTP. AB - Protein tyrosine phosphatase 1B (PTP1B) has already been well studied as a highly validated therapeutic target for diabetes and obesity. However, the lack of selectivity limited further studies and clinical applications of PTP1B inhibitors, especially over T-cell protein tyrosine phosphatase (TCPTP). In this review, we enumerate the published specific inhibitors of PTP1B, discuss the structure-activity relationships by analysis of their X-ray structures or docking results, and summarize the characteristic of selectivity related residues and groups. Furthermore, the design strategy of selective PTP1B inhibitors over TCPTP is also proposed. We hope our work could provide an effective way to gain specific PTP1B inhibitors. PMID- 27353890 TI - A comparison between physicians and computer algorithms for form CMS-2728 data reporting. AB - INTRODUCTION: CMS-2728 form (Medical Evidence Report) assesses 23 comorbidities chosen to reflect poor outcomes and increased mortality risk. Previous studies questioned the validity of physician reporting on forms CMS-2728. We hypothesize that reporting of comorbidities by computer algorithms identifies more comorbidities than physician completion, and, therefore, is more reflective of underlying disease burden. METHODS: We collected data from CMS-2728 forms for all 296 patients who had incident ESRD diagnosis and received chronic dialysis from 2005 through 2014 at Indiana University outpatient dialysis centers. We analyzed patients' data from electronic medical records systems that collated information from multiple health care sources. Previously utilized algorithms or natural language processing was used to extract data on 10 comorbidities for a period of up to 10 years prior to ESRD incidence. These algorithms incorporate billing codes, prescriptions, and other relevant elements. We compared the presence or unchecked status of these comorbidities on the forms to the presence or absence according to the algorithms. FINDINGS: Computer algorithms had higher reporting of comorbidities compared to forms completion by physicians. This remained true when decreasing data span to one year and using only a single health center source. The algorithms determination was well accepted by a physician panel. Importantly, algorithms use significantly increased the expected deaths and lowered the standardized mortality ratios. DISCUSSION: Using computer algorithms showed superior identification of comorbidities for form CMS-2728 and altered standardized mortality ratios. Adapting similar algorithms in available EMR systems may offer more thorough evaluation of comorbidities and improve quality reporting. PMID- 27353891 TI - Unusual distance dependences of electron transfer rates. AB - Usually the rates for electron transfer (kET) decrease with increasing donor acceptor distance, but Marcus theory predicts a regime in which kET is expected to increase when the transfer distance gets longer. Until recently, experimental evidence for such counter-intuitive behavior had been very limited, and consequently this effect is much less well-known than the Gaussian free energy dependence of electron transfer rates leading to the so-called inverted driving force effect. This article presents the theoretical concepts that lead to the prediction of electron transfer rate maxima at large donor-acceptor distances, and it discusses conditions that are expected to favor experimental observations of such behavior. It continues with a consideration of specific recent examples in which electron transfer rates were observed to increase with increasing donor acceptor distance, and it closes with a discussion of the importance of this effect in the context of light-to-chemical energy conversion. PMID- 27353892 TI - Brexit: what are the implications for nurses? AB - The referendum result is in and appears to have caught the nation by surprise. Whatever the fallout from voters' decision to leave the EU, the implications for nursing are likely to be widespread and profound - and could take years to resolve. PMID- 27353893 TI - Chief nurse reassures EU workers after Brexit vote. AB - European Union nurses remain 'an integral and appreciated' part of the NHS, England's chief nurse has said in the wake of the UK's Brexit vote. PMID- 27353894 TI - Nottingham tram named after award-winning nurse. AB - A theatre recovery nurse will travel to work in style from now on after having a tram named in her honour. PMID- 27353895 TI - MP asks Hunt about nurse advice unit cuts. AB - Pressure is mounting on the Department of Health to reconsider its controversial plan to axe its team of nurse advisers. PMID- 27353896 TI - Call for rent controls as nursing staff struggle to find affordable housing. AB - Nurses priced out of affordable homes are risking their health driving long distances home after shifts, RCN congress heard last week. PMID- 27353897 TI - Sculptor unfazed by Seacole statue backlash. AB - The backlash against the soon to be unveiled Mary Seacole statue is 'a storm in a bedpan', according to the artist behind it. PMID- 27353898 TI - Students share their views of funding plans. AB - The chief nursing officer for England has met with nursing students to hear first hand their views on government proposals to cut NHS bursaries. PMID- 27353900 TI - Backing public health will save money in long term. AB - Cuts to the public health budget have been condemned as illogical and short sighted by nurses. PMID- 27353903 TI - Streamling ruling council from 31 to 17 gets backing at RCN's AGM. AB - RCN members have backed changes to the way their ruling council is run, aimed at making it more streamlined and effective - but only after a row at the annual general meeting (AGM). PMID- 27353904 TI - Images of nursing impress judges of national photographic competition. AB - A photograph showing a violin-playing patient surrounded by his hospital nursing team has won its taker an award in a national photographic competition. PMID- 27353905 TI - What does Brexit mean for nursing and our EU staff? AB - Currently there is free movement of labour and mutual recognition of nurse training and qualifications between EU member states. This means UK hospitals can actively recruit nurses from across the EU to cover staff shortfalls. So what now? PMID- 27353908 TI - Neonatal jaundice. AB - Essential facts Jaundice is one of the most common conditions affecting newborn babies. It is estimated that 6 out of every 10 babies develop jaundice, with even higher rates for premature babies. Caused by increased levels of bilirubin in the blood, jaundice is generally harmless, and resolves without treatment by 2 weeks of age. However, high levels of bilirubin can be harmful if not treated and need to be identified quickly. PMID- 27353909 TI - Expressing anger positively could reduce eating disorders in women. AB - Lessons on how to express anger in direct and positive ways could help reduce eating disorders in girls, say researchers. PMID- 27353910 TI - Lung cancer patients could be given choice over treatment. AB - Having radiotherapy once a day for 6.5 weeks, or twice a day for 3 weeks - when combined with chemotherapy - is equally good at treating small cell lung cancer that has not spread, a study suggests. PMID- 27353911 TI - Migraines linked to heart attacks in women. AB - Women who experience migraines have an increased risk of developing cardiovascular diseases such as heart attacks and strokes, say researchers. PMID- 27353913 TI - Telephone follow-up reduces anxiety in burns patients. AB - A tailored education programme for people who have experienced burns can help reduce symptoms of anxiety and post-traumatic stress, a new study suggests. PMID- 27353914 TI - Inspirational, meaningful care quality nursing across Scotland. AB - In Scotland, geography and social conditions are placing demands on nurses' ingenuity. As RCN Scotland Director Theresa Fyffe says: 'Nurses in Scotland are constantly overcoming the challenges thrown at them by our health and social care system and diverse geography. PMID- 27353915 TI - Hub eases strain on primary care. AB - It is widely acknowledged that NHS primary care services are struggling to cope with demand. NHS England's General Practice Forward View, published in April, highlights 'unprecedented pressure on practices, which impacts on staff and patients'. It also points out that small changes in GP capacity have a big effect on demand for hospital care. PMID- 27353916 TI - Time to market nursing. AB - For too long nursing has been seen as a cost rather than a way of providing efficient and cost-effective care. My hope is that the nursing framework, Leading Change, Adding Value, will help nurses re-establish their place in the system. PMID- 27353918 TI - The NMC has to look beyond England, says Janet Finch. AB - The Nursing and Midwifery Council is a 4-country regulator. Our remit covers Wales, Scotland, Northern Ireland and England, which is reflected in the membership of our council and many of our activities. PMID- 27353917 TI - Let's not forget attrition. AB - The heated debate about the ending of bursaries for nursing students has given scant attention to one important issue: drop-out rates. PMID- 27353919 TI - Look again at psychedelic drugs. AB - The World Health Organization recommends that anxiety, depression, agitation and delirium at end of life should be treated with drugs such as lorazepam, diazepam, midazolam and haloperidol. PMID- 27353920 TI - How do nurses feed a family? AB - Imposing student loans without consultation means nurses taking on a burden of debt that may never be repaid, with a negative effect on all with domestic or caring responsibilities. The student loan will take care of tuition fees, but what about feeding the family and keeping a roof over their heads? PMID- 27353921 TI - Doormen are the answer. AB - I'd like to see a doorman at every emergency department to support often distraught people on arrival. It is about making people's lives easier and would also help lower aggression and violence against staff. PMID- 27353924 TI - Senior nurses are critical. AB - Pressures on health and social care have never been greater. This month Nigel Edwards, chief executive of the respected Nuffield Trust, cautioned that NHS morale was at an all-time low, posing a threat at least as great as financial constraints. PMID- 27353925 TI - Readers' panel - Should nurses be prosecuted if they fail to report child abuse? AB - Our experts consider a hot topic of the day. PMID- 27353926 TI - Medical reality dramas do not show the real NHS. AB - My other half likes those medical reality programmes, whereas I would rather stick my head in the oven than watch anything to do with work. PMID- 27353929 TI - Know Your DAS. AB - The Know Your DAS app, created by the National Rheumatoid Arthritis Society, monitors users' rheumatoid arthritis (RA) in between consultations by prompting them to complete a self-assessment. PMID- 27353930 TI - A passport to better care. AB - Having worked as a healthcare assistant (HCA) for almost 20 years, Lorraine Ramnath found training to become a nurse at the Open University gave her a new insight into patient care. PMID- 27353931 TI - Never underestimate the importance of hand holding. AB - During a shift on a ward, it is easy to get overwhelmed with paperwork, checklists and practices such as infection control. These exist to keep patients and staff safe, but sometimes patients just need human contact to take them through what can be a traumatic time. PMID- 27353932 TI - Changing perceptions on flexible working is the way. AB - Research from Bradford University has shone new light on the dilemma of how nurses struggle to reconcile professional duties and family commitments, suggesting that some of the resistance to making the career more accessible for women with young children is coming from other female nurses. PMID- 27353933 TI - Whoever holds the purse strings holds the power. AB - An average ward has a budget of about L1 million a year for staffing and supplies. With responsibility for its allocation often with the ward manager or sister, budgeting skills are essential. PMID- 27353934 TI - 'Have confidence in yourself'. AB - Former director of nursing at Royal Brompton & Harefield NHS Foundation Trust Caroline Shuldham OBE left the NHS last year to work independently. She celebrates 45 years in nursing this year and is involved in research, teaching, mentoring, inspection and advising on care. PMID- 27353935 TI - How to record and evidence continuing professional development for revalidation. AB - Rationale and key points This is the third in a series of eight articles providing information about the Nursing and Midwifery Council (NMC) revalidation process. This article focuses on recording and providing evidence of continuing professional development (CPD). Nurses and midwives must have undertaken 35 hours of CPD, of which at least 20 hours must have included participatory learning, relevant to their scope of practice, in the 3-year period since their registration was last renewed or they joined the register. " CPD enables nurses and midwives to ensure their knowledge and skills are up to date. " The participatory component of CPD encourages engagement and communication with others, thus challenging professional isolation. Reflective activity 'How to' revalidate articles can help to update your practice and provide information about the revalidation process, including how you can record and evidence CPD for revalidation. Reflect on and write a short account of: 1. How recording and evidencing CPD will demonstrate the skills, knowledge and experience you have gained in practice. 2. How you could use this article to educate your colleagues. Subscribers can update their reflective accounts at: rcni.com/portfolio. PMID- 27353936 TI - Legal and ethical issues in neonatal nursing: a case study. AB - Neonatal nurses regularly face complex legal and ethical dilemmas. This article discusses the hypothetical case of Jack, a two-day-old infant diagnosed with trisomy 13 (syndrome), a life-limiting condition. Jack's prognosis is poor, and he is not expected to live past two weeks of age. The legal and ethical perspectives of withholding life-sustaining treatment in infants and children will be explored through the application of ethical frameworks, as well as statute and case law relevant to children and adolescent nursing. The article also discusses the neonatal nurse's role, with reference to local and national guidelines. PMID- 27353938 TI - Medicines optimisation. AB - What was the nature of the CPD activity and/or practice-related feedback and/or event or experience in your practice? The CPD article outlined the priorities and challenges of medicines optimisation, which is a person-centred approach to safe and effective medicines use. The aim is for the patient to achieve the best possible outcomes from their medicines. PMID- 27353937 TI - Palliative and end-of-life care for people living with dementia in care homes: part 2. AB - This article, the second of two, provides healthcare practitioners with an overview of best practice in palliative and end-of-life care, including nutrition, hydration, oral hygiene and pain management. Communication and spiritual care are discussed, as well as care after death. Providing support and education for families is an important aspect of palliative and end-of-life care. Care home nurses should ensure that the person living with dementia is at the centre of decision making, and provide care that is inclusive of their needs and wishes. The article is framed in a care home context; there is little research about how to optimise palliative care for people living with dementia in care homes. PMID- 27353939 TI - 'Cathy became my confidante'. AB - I was wary of a respiratory nurse becoming involved in my care. I had a good relationship with the respiratory consultants and, although I was unwell and things were difficult, I did not see what another nurse could add. I could not have been more wrong. PMID- 27353940 TI - Nurses lead on waste reduction. AB - Waste in the NHS accounts for about 20% of health expenditure. This article examines the literature on reducing waste, analyses some approaches to waste reduction, and identifies the role of nurses and other health professionals in developing a sustainable NHS. PMID- 27353941 TI - Violence against older women. AB - Domestic abuse is widespread and indiscriminate. Older women living with domestic abuse experience a number of health-related concerns and significant mental health issues. PMID- 27353942 TI - Depression in transition to becoming a new father. AB - Over the past three decades, there has been a growing awareness about the burden of ill-health experienced by men. PMID- 27353943 TI - Public health spend. AB - 'Spending on public health offers the best value for public money. We should fund more and spend more on public health, not less'. PMID- 27353944 TI - Nutrition. AB - Staff supporting people with dementia to eat should take part in face-to-face education programmes. PMID- 27353945 TI - Presidential address: Experimenting with the scientific past. AB - When it comes to knowledge about the scientific pasts that might have been - the so-called 'counterfactual' history of science - historians can either debate its possibility or get on with the job. Taking the latter course means re-engaging with some of the most general questions about science. It can also lead to fresh insights into why particular episodes unfolded as they did and not otherwise. Drawing on recent research into the controversy over Mendelism in the early twentieth century, this address reports and reflects on a novel teaching experiment conducted in order to find out what biology and its students might be like now had the controversy gone differently. The results suggest a number of new options: for the collection of evidence about the counterfactual scientific past, for the development of collaborations between historians of science and science educators, for the cultivation of more productive relationships between scientists and their forebears, and for heightened self-awareness about the curiously counterfactual business of being historical. PMID- 27353946 TI - Film lessons: early cinema for historians of science. AB - Despite much excellent work over the years, the vast history of scientific filmmaking is still largely unknown. Historians of science have long been concerned with visual culture, communication and the public sphere on the one hand, and with expertise, knowledge production and experimental practice on the other. Scientists, we know, drew pictures, took photographs and made three dimensional models. Rather like models, films could not be printed in journals until the digital era, and this limited their usefulness as evidence. But that did not stop researchers from making movies for projection at conferences as well as in lecture halls, museums and other public venues, not to mention for breaking down into individual frames for analysis. Historians of science are more likely to be found in the library, archive or museum than the darkened screening room, and much work is still needed to demonstrate the major effects of cinema on scientific knowledge. Film may have taken as long to change science as other areas of social life, but one can begin to glimpse important ways in which 'image machines' (cameras, projectors and the like) were beginning to mediate between backstage experimental work and more public demonstration even around 1900. PMID- 27353947 TI - Next generation sequencing based identification of disease-associated mutations in Swiss patients with retinal dystrophies. AB - Inherited monogenic diseases of the retina and vitreous affect approximately 1 in 2000 individuals. They are characterized by tremendous genetic heterogeneity and clinical variability involving mutations in approximately 250 genes and more than 20 different clinical phenotypes. Clinical manifestations of retinal dystrophies (RDs) range from mild retinal dysfunctions to severe congenital forms of blindness. A detailed clinical diagnosis and the identification of causative mutations are crucial for genetic counseling of affected patients and their families, for understanding genotype-phenotype correlations and developing therapeutic approaches. Using whole exome sequencing (WES) we have established a reliable and efficient high-throughput analysis pipeline to identify disease causing mutations. Our data indicate that this approach enables us to genetically diagnose approximately 64% of the patients (n = 58) with variant(s) in known disease-associated genes. We report 20 novel and 26 recurrent variants in genes associated with RDs. We also identified a novel phenotype for mutations in C2orf71 and provide functional evidence for exon skipping due to a splice-site variant identified in FLVCR1. In conclusion, WES can rapidly identify variants in various families affected with different forms of RDs. Our study also expands the clinical and allelic spectrum of genes associated with RDs in the Swiss population. PMID- 27353948 TI - Development and Validation of a Pediatric Endocrine Knowledge Assessment Questionnaire: Impact of ac Pediatric Endocrine Knowledge Assessment Questionnaire Intervention Study. AB - OBJECTIVE: While there is general agreement that patient education is essential for compliance, no objective tools exist to assess knowledge in children and parents of children with endocrine disorders. We aimed to design and validate a Pediatric Endocrine Knowledge Assessment Questionnaire (PEKAQ) for congenital hypothyroidism, Hashimoto's thyroiditis, isolated growth hormone deficiency, Graves' disease, and congenital adrenal hyperplasia. We evaluated baseline knowledge of children and parents of children with these disorders and assessed impact of educational intervention. METHODS: At baseline, 77 children (12-18 years) and 162 parents of children 1-18 years participated in this prospective intervention study. Educational handouts for five targeted disorders were designed. Following one-on-one educational intervention, 55 children and 123 parents participated. Baseline and post-intervention knowledge scores were compared using McNemar's test. RESULTS: Adequate multi-rater Kappa measure of agreement was achieved for children's (0.70) and parent's (0.75) PEKAQs. Flesch Reading Ease Score for both PEKAQs (15 questions each) was 65. Post-intervention, significantly higher proportion of parents and children answered majority of questions correctly (p<0.05). Sixteen percent more parents and 22% more children knew their diagnosis correctly (p<0.05). Significant improvement was noted among all participants regarding reason for treatment, steps to take in a situation of missed dose, exercise and diet with these disorders, and long-term prognosis. Parent's knowledge score was an independent predictor of child's score. CONCLUSIONS: To our knowledge, this is the first validated PEKAQ that can be used widely in pediatric endocrinology clinics. We noted significant improvement in knowledge of children and parents of children with endocrine disorders. PMID- 27353949 TI - Development of Cutaneous Toxicities During Selective Anti-BRAF Therapies: Preventive Role of Combination with MEK Inhibitors. PMID- 27353950 TI - Restricted distribution and lateralization of mutualistic Wolbachia in the Drosophila brain. AB - Microbial symbionts are universal entities of all living organisms that can significantly affect host fitness traits in manifold ways but, even more fascinating, also their behaviour. Although better known from parasitic symbionts, we currently lack any cases where 'neurotrophic' symbionts have co evolved mutualistic behavioural interactions from which both partners profit. By theory, most mutualistic associations have originated from ancestral parasitic ones during their long-term co-evolution towards a cost-benefit equilibrium. To manipulate host behaviour in a way where both partners benefit in a reciprocal manner, the symbiont has to target and remain restricted to defined host brain regions to minimize unnecessary fitness costs. By using the classic Drosophila paulistorum model system we demonstrate that (i) mutualistic Wolbachia are restricted to various Drosophila brain areas, (ii) form bacteriocyte-like structures within the brain, (iii) exhibit strictly lateral tropism, and (iv) finally propose that their selective neuronal infection affects host sexual behaviour adaptively. PMID- 27353952 TI - Role of compassion competence among clinical nurses in professional quality of life. AB - AIM: The study aimed to explore measurable compassion competence among nurses and to examine the relationships between nurses' compassion competence and levels of compassion satisfaction, compassion fatigue and secondary traumatic stress. BACKGROUND: Compassion is a vital asset in the nursing profession. It is necessary to explore whether compassion competence is a factor influencing professional quality of life. METHODS: This study utilized a multicenter descriptive cross-sectional survey. Data were collected from 680 nurses. RESULTS: Professional quality of life based on nurses' general characteristics showed a significant difference in the subjects' age, marital status, education, and total clinical experience. In addition, compassion competence had a significant positive correlation with compassion satisfaction and STS, whereas it had a significant negative correlation with burnout. Compassion competence was a factor influencing compassion satisfaction and burnout in professional quality of life. LIMITATIONS: Our study included nurses with at least 1 year of clinical experience in a single cultural area, which limits its widespread applicability. To improve generalizability, future studies should include clinical nurses of various races, working in diverse cultural areas and with various levels of experience (including entry-level nurses and nursing students). CONCLUSION AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: Compassion competence of clinical nurses was a predictive factor for professional quality of life. Hospital administrators, nurse leaders and policy makers should develop and adopt nurse retaining strategies that focus on improving nurses' compassion competence in order to reduce their burnout. We recommend the development of educational programmes to improve nurses' compassion competence and thereby enhance their professional quality of life. PMID- 27353951 TI - Mucous membrane pemphigoid in dogs: a retrospective study of 16 new cases. AB - BACKGROUND: Mucous membrane pemphigoid (MMP) is a chronic autoimmune subepidermal blistering disease of dogs, cats and humans. OBJECTIVES: The goal of this study was to describe the clinical, histological and immunological features and treatment outcomes of canine MMP. ANIMALS: Sixteen dogs were diagnosed with MMP based on the presence of mucosal- or mucocutaneous-predominant vesiculation and/or ulceration, histological confirmation of subepidermal clefting and an age of disease onset greater than 6 months. RESULTS: Six of 16 dogs (38%) were German shepherd dogs and their crosses. The median age of disease onset was 6 years (range: 1-10 years). At the time of presentation, the dogs exhibited erosions and ulcers in the oral cavity (11 of 16; 69%), nasal (nine of 16; 56%), periocular (eight of 16; 50%) and genital (six of 16; 38%) regions. Haired skin lesions were less frequent (six of 16; 38%) and involved mostly concave pinnae. Information on treatment outcome was available for 11 dogs (69%). A complete remission (CR) of lesions was achieved in 10 of 11 dogs (91%). The median time to CR was 33 weeks (range: 6-64 weeks). Treatment regimens varied widely but six of 10 (60%) dogs received a combination of tetracycline antibiotic and niacinamide alone, or with another drug, at the time of CR. Forty percent of the dogs in which CR had occurred experienced lesion relapse upon drug dose reduction. CONCLUSIONS AND CLINICAL IMPORTANCE: Canine MMP is a chronic and relapsing disease requiring long term treatment. Combination therapy is often needed to achieve CR. PMID- 27353953 TI - Impaired orexin receptor expression in the Kolliker-Fuse nucleus in sudden infant death syndrome: possible involvement of this nucleus in arousal pathophysiology. AB - OBJECTIVES: As well known, the sudden infant death syndrome (SIDS) is characterized by the sudden death of a seemingly healthy infant during sleep, frequently resulted from a deficit in arousal phase. Awakening from sleep requires a fully developed and functioning neuronal respiratory network to modulate the ventilation as needed. The pontine Kolliker-Fuse nucleus (KFN) plays a pivotal role in breathing control, thanks to its interconnections with the widespread serotonin and noradrenaline neurons in the brainstem. Numerous studies to date have focused on the implication of orexin, a neuropeptide synthesized by neurons of the lateral hypothalamus, with major projections to the brainstem raphe nuclei and locus coeruleus, in arousal, a neurobiological process closely linked to breathing modifications. The aim of our research has been to demonstrate that also the KFN is a fundamental component of the orexin system, actively involved in arousal. METHODS: We have evaluated the expression and distribution of the orexin receptors (orexin-1 and orexin-2 receptors) particularly in the rostral pons, where the KFN is located, of 25 SIDS cases and 18 controls. RESULTS: An intense orexin-1 innervation around the KF neurons has been detected in almost all the controls and only in 20% of SIDS cases. DISCUSSION: On the basis of these results, we believe that: (1) the KFN plays a leading role not only in providing a regular breathing rhythm but also in the coordination of the sleep-to-wake transition; (2) a defective orexin expression in the KFN could prevent arousal, thus assuming a crucial importance in causing SIDS. PMID- 27353954 TI - PUFA and oxidative stress. Differential modulation of the cell response by DHA. AB - Although an increased dietary intake of long-chain n-3 PUFA is considered an effective preventive strategy, a theoretical concern related to the possible increase of lipid peroxidation induced by a PUFA-rich diet still remains a problem. In this study, the effects of different PUFA (linoleic, alpha-linolenic, arachidonic, eicosapentaenoic and docosahexaenoic acid) on cytotoxicity, lipid oxidation, and modulation of antioxidant defenses were evaluated in HepG2 cells submitted to an oxidative stress (H2O2). Results clearly evidenced that all supplemented PUFA, but DHA, enhanced cell susceptibility to H2O2. Overall, our results underline that PUFA cannot be considered as a single category but as individual compounds, and research on mechanisms of action and preventive effects should deal with the individual fatty acids, particularly in the case of DHA. PMID- 27353955 TI - Changing paradigm in mild traumatic brain injury research. PMID- 27353956 TI - Population pharmacokinetic modelling of factor IX activity after administration of recombinant factor IX in patients with haemophilia B. AB - PURPOSE: The aim is to develop a pharmacokinetic model for factor IX activity (FIX) after BeneFIX (nonacog alfa, rFIX) administration and assess potential covariates using all available clinical data collected during development. METHODS: The data set for model development combined observations from eight studies. Postdose FIX observations were adjusted by subtracting predose FIX if these were above the lower limit of quantification (BLQ) and all BLQ observations were removed. A population pharmacokinetic model was then developed with 4936 observations from 201 patients. Two additional studies (385 observations from 72 patients) became available and were used to evaluate the model. RESULTS: A two compartment model, parameterized for clearance (CL), volume of distribution of the central (V1) and peripheral (V2) compartments, and intercompartmental clearance (Q), with an effect of weight on all parameters was the final model. Weight was incorporated as a power function with exponent estimates close to conventional allometric scaling. Including interoccasion variability (IOV) on CL and V1 showed decreases in the objective function. Investigations of a full block omega matrix lead to the retention of a correlation between V2 and Q. Age was not a significant covariate with weight already included in the model. Observations in the studies used for evaluation were found to be higher than simulated values immediately after dosing, as well as a week after dosing. The differences may be due perhaps to differences in the patients enrolled in the evaluation studies (all were adults) as well as the sample collection time after dosing (longer after dosing in the evaluation studies). CONCLUSIONS: FIX is appropriately modelled as a two-compartment model after rFIX administration. When weight is included, no additional effect of age is observed. Longer times of observation after dosing may be helpful in refining the model. PMID- 27353958 TI - Retraction of "Impact of Natural Gas Extraction on PAH Levels in Ambient Air". PMID- 27353959 TI - The short-term association between meteorological factors and mumps in Jining, China. AB - BACKGROUND: An increasing trend of the incidence of mumps has been observed in a few developing countries in recent years, presenting a major threat to children's health. A few studies have examined the relationship between meteorological factors and mumps with inconsistent findings. METHODS: The daily data of meteorological variables and mumps from 2009 to 2013 were obtained from Jining, a temperate inland city of China. A generalized additive model was used to quantify the association between meteorological factors and mumps based on the exposure response relationship. RESULTS: A total of 8520 mumps cases were included in this study. We found a nonlinear relationship of daily mean temperature, sunshine duration and relative humidity with mumps, with an approximately linear association for mean temperature above 4 degrees C (excess risk (ER) for 1 degrees C increase was 2.72%, 95% confidence interval (CI): 2.38%, 3.05% on the current day), for relative humidity above 54%, the ER for 1% increase was -1.86% (95% CI: -2.06%, -1.65%) at lag day 14; and for sunshine duration higher than 5h/d, the ER for per 1h/d increase was12.91% (95% CI: 11.38%, 14.47%) at lag day 1. While we found linear effects for daily wind speed (ER: 2.98%, 95% CI: 2.71%, 3.26% at lag day 13). CONCLUSIONS: This study suggests that meteorological factors might be important predictors of incidence of mumps, and should be considered in its control and prevention. PMID- 27353957 TI - NMR Characterization of Information Flow and Allosteric Communities in the MAP Kinase p38gamma. AB - The intramolecular network structure of a protein provides valuable insights into allosteric sites and communication pathways. However, a straightforward method to comprehensively map and characterize these pathways is not currently available. Here we present an approach to characterize intramolecular network structure using NMR chemical shift perturbations. We apply the method to the mitogen activated protein kinase (MAPK) p38gamma. p38gamma contains allosteric sites that are conserved among eukaryotic kinases as well as unique to the MAPK family. How these regulatory sites communicate with catalytic residues is not well understood. Using our method, we observe and characterize for the first time information flux between regulatory sites through a conserved kinase infrastructure. This network is accessed, reinforced, and broken in various states of p38gamma, reflecting the functional state of the protein. We demonstrate that the approach detects critical junctions in the network corresponding to biologically significant allosteric sites and pathways. PMID- 27353960 TI - The cbfs triple mutants reveal the essential functions of CBFs in cold acclimation and allow the definition of CBF regulons in Arabidopsis. AB - In Arabidopsis, the C-repeat binding factors (CBFs) have been extensively studied as key transcription factors in the cold stress response. However, their exact functions in the cold response remains unclear due to the lack of a null cbf triple mutant. In this study, we used CRISPR/Cas9 technology to mutate CBF1 or CBF1/CBF2 in a cbf3 T-DNA insertion mutant to generate cbf1,3 double and cbf1 cbf2 cbf3 (cbfs) triple mutants. The response of the cbfs triple mutants to chilling stress is impaired. Furthermore, no significant difference in freezing tolerance was observed between the wild-type and the cbf1,3 and cbfs mutants without cold acclimation. However, the cbfs mutants were extremely sensitive to freezing stress after cold acclimation, and freezing sensitivity ranking was cbfs > cbf1,3 > cbf3. RNA-Seq analysis showed that 134 genes were CBF regulated, of which 112 were regulated positively and 22 negatively by CBFs. Our study reveals the essential functions of CBFs in chilling stress response and cold acclimation, as well as defines a set of genes as CBF regulon. It also provides materials for the genetic dissection of components in CBF-dependent cold signaling. PMID- 27353961 TI - Re: alpha1-Blockers Improve Benign Prostatic Obstruction in Men with Lower Urinary Tract Symptoms: A Systematic Review and Meta-analysis of Urodynamic Studies. PMID- 27353962 TI - Words of Wisdom. PMID- 27353963 TI - Re: Failure-Free Survival and Radiotherapy in Patients with Newly Diagnosed Nonmetastatic Prostate Cancer: Data from Patients in the Control Arm of the STAMPEDE Trial. PMID- 27353964 TI - Re: Robot-assisted Versus Open Radical Prostatectomy: A Contemporary Analysis of an All-payer Discharge Database. PMID- 27353965 TI - Re: Vinflunine-gemcitabine Versus Vinflunine-carboplatin as First-line Chemotherapy in Cisplatin-unfit Patients with Advanced Urothelial Carcinoma: Results of an International Randomized Phase II Trial (JASINT1). PMID- 27353966 TI - Re: Comprehensive Genomic Profiling of 295 Cases of Clinically Advanced Urothelial Carcinoma of the Urinary Bladder Reveals a High Frequency of Clinically Relevant Genomic Alterations. PMID- 27353967 TI - Re: Kidney-Failure Risk Projection for the Living Kidney-Donor Candidate. PMID- 27353968 TI - Role of CA3 theta-modulated interneurons during the transition to spontaneous seizures. AB - Multiple studies have observed heterogeneous neuronal firing patterns as a local network transitions to spontaneous seizures. We demonstrated that separately examining interneurons and pyramidal cells during this transition in a rat model of temporal lobe epilepsy elucidates some of this heterogeneity. Recently, it was demonstrated that classifying cells into specific theta-related subtypes further clarified the heterogeneity. Moreover, changes in neuronal synchrony with the local field potential were identified and determined to be specific to interneurons during the transition to seizures. To extend our understanding of the chronic changes in epileptic networks, we examined field potentials and single neuron activity in the CA3 hippocampus of pilocarpine-treated rats during interictal periods and compared these to neuronal activity in healthy controls and during preictal periods. Neurons were classified into theta-subtypes based on changes in firing patterns during theta periods. As previously reported, we find a high probability of theta oscillations before seizure onset and a selective increase in theta-on interneuron firing rate immediately preceding seizure onset. However, we also find overall slower theta rhythm and a general decrease in subtype-specific firing during interictal periods compared to that in control animals. The decrease in subtype specific interneuron activity is accompanied by increases in synchrony. Exceptionally, theta-on interneurons, that selectively increase their firing rate at seizure onset, maintain similar firing rates and synchrony as controls during interictal period. These data suggest that increased synchrony during interictal periods may compensate for low firing rates creating instability during theta that is prone to seizure initiation via a transition to hyper-synchronous activation of theta-on interneurons. PMID- 27353969 TI - Association of visual sensory function and higher-order visual processing skills with incident driving cessation. AB - BACKGROUND: Many studies on vision and driving cessation have relied on measures of sensory function, which are insensitive to the higher-order cognitive aspects of visual processing. The purpose of this study was to examine the association between traditional measures of visual sensory function and higher-order visual processing skills with incident driving cessation in a population-based sample of older drivers. METHODS: Two thousand licensed drivers aged 70 years or older were enrolled and followed for three years. Tests for central vision and visual processing were administered at baseline and included visual acuity, contrast sensitivity, sensitivity in the driving visual field, visual processing speed (useful field of view [UFOV] Subtest 2 and Trails B) and spatial ability measured by the Visual Closure Subtest of the Motor-free Visual Perception Test. Participants self-reported the month and year of driving cessation and provided a reason for cessation. Cox proportional hazards models were used to generate crude and adjusted hazard ratios with 95% confidence intervals between visual functioning characteristics and risk of driving cessation over a three-year period. RESULTS: During the study period, 164 participants stopped driving, which corresponds to a cumulative incidence of 8.5 per cent. Impaired contrast sensitivity, visual fields, visual processing speed (UFOV and Trails B) and spatial ability were significant risk factors for subsequent driving cessation after adjusting for age, gender, marital status, number of medical conditions and miles driven. Visual acuity impairment was not associated with driving cessation. Medical problems (63 per cent), specifically musculoskeletal and neurological problems, as well as visual problems (17 per cent) were cited most frequently as the reason for driving cessation. CONCLUSION: Assessment of cognitive and visual functioning can provide useful information about subsequent risk of driving cessation among older drivers. In addition, a variety of factors, not just vision, influenced the decision to stop driving and may be amenable to intervention. PMID- 27353970 TI - Dynamic functional connectivity shapes individual differences in associative learning. AB - Current neuroscientific research has shown that the brain reconfigures its functional interactions at multiple timescales. Here, we sought to link transient changes in functional brain networks to individual differences in behavioral and cognitive performance by using an active learning paradigm. Participants learned associations between pairs of unrelated visual stimuli by using feedback. Interindividual behavioral variability was quantified with a learning rate measure. By using a multivariate statistical framework (partial least squares), we identified patterns of network organization across multiple temporal scales (within a trial, millisecond; across a learning session, minute) and linked these to the rate of change in behavioral performance (fast and slow). Results indicated that posterior network connectivity was present early in the trial for fast, and later in the trial for slow performers. In contrast, connectivity in an associative memory network (frontal, striatal, and medial temporal regions) occurred later in the trial for fast, and earlier for slow performers. Time dependent changes in the posterior network were correlated with visual/spatial scores obtained from independent neuropsychological assessments, with fast learners performing better on visual/spatial subtests. No relationship was found between functional connectivity dynamics in the memory network and visual/spatial test scores indicative of cognitive skill. By using a comprehensive set of measures (behavioral, cognitive, and neurophysiological), we report that individual variations in learning-related performance change are supported by differences in cognitive ability and time-sensitive connectivity in functional neural networks. Hum Brain Mapp 37:3911-3928, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27353971 TI - Using the gini coefficient to measure the chemical diversity of small-molecule libraries. AB - Modern databases of small organic molecules contain tens of millions of structures. The size of theoretically available chemistry is even larger. However, despite the large amount of chemical information, the "big data" moment for chemistry has not yet provided the corresponding payoff of cheaper computer predicted medicine or robust machine-learning models for the determination of efficacy and toxicity. Here, we present a study of the diversity of chemical datasets using a measure that is commonly used in socioeconomic studies. We demonstrate the use of this diversity measure on several datasets that were constructed to contain various congeneric subsets of molecules as well as randomly selected molecules. We also apply our method to a number of well-known databases that are frequently used for structure-activity relationship modeling. Our results show the poor diversity of the common sources of potential lead compounds compared to actual known drugs. (c) 2016 Wiley Periodicals, Inc. PMID- 27353972 TI - [Professional discourses on intimate partner violence: implication for care of immigrant women in Spain]. AB - OBJECTIVE: 1) to examine the discourses of professionals involved in the care of female victims of intimate partner violence (IPV), with emphasis on how they describe the immigrant women, the perpetrators and their own responsibility of care; and 2) to compare these discourses with the other professions involved in caring for these women (social services, associations and police and justice). METHODS: Qualitative study based on semi-structured interviews with 43 professionals from social services, associations and the police and judicial systems. A discourse analysis was carried out to identify interpretive repertoires about IPV, immigrant women and their aggressors, their culture and professional practices. RESULTS: Four interpretive repertoires emerged from professional discourses: "Cultural prototypes of women affected by IPV", "Perpetrators are similar regardless of their culture of origin", "Are victims credible and the perpetrators responsible?" and "Lack of cultural sensitivity of professionals in helping immigrant women in abusive situations". These repertoires correspond to preconceptions that professionals construct about affected women and their perpetrators, the credibility and responsibility they attribute to them and the interpretation of their professional roles. CONCLUSIONS: The employment of IPV-trained cultural mediators in the services responsible for caring for the female victims, together with cultural training for the professionals, will facilitate the provision of culturally sensitive care to immigrant female victims of intimate partner violence. PMID- 27353974 TI - A single-step acid catalyzed reaction for rapid assembly of NH-1,2,3-triazoles. AB - NH-1,2,3-Triazole moieties are a part of the design of various biologically active compounds, pharmaceutical agents and functional materials. Unfortunately, the applications of this heterocycle are still underexplored due to the lack of a general synthetic protocol. Here we outline a novel, general and facile metal free pathway that enables the direct synthesis of these heterocycles by combining readily accessible and abundant precursors such as enolizable ketones and NH4OAc with high levels of regioselectivity via an organocascade process. The developed chemistry has been successfully applied to the synthesis of several structurally diverse products, pharmaceutical agents and supramolecular receptors. PMID- 27353973 TI - Usefulness of fetal autopsy in the diagnosis of blomstrand chondrodysplasia: a report of three cases. AB - Blomstrand osteochondrodysplasia (BOCD) is a rare autosomal recessive sclerosing skeletal dysplasia characterized by accelerated chondrocyte differentiation. In this article, we discuss three cases where lethal skeletal dysplasia was suspected and Blomstrand dysplasia was diagnosed by autopsy. Antenatal ultrasound findings include increased nuchal translucency, tetramicromelia and polyhydramnios. Radiological hallmark is advanced skeletal maturation and bone sclerosis. Histology of long bones revealed narrow cartilagenous cap and changes in the physeal growth zone which showed severe hypoplasia and disorganization of proliferative phase and hypertrophic phase. Homozygous and compound heterozygous mutations in PTHR1 gene have been implicated in the pathogenesis of this chondrodysplasia. PMID- 27353975 TI - The PaPsr1 and PaWhi2 genes are members of the regulatory network that connect stationary phase to mycelium differentiation and reproduction in Podospora anserina. AB - In filamentous fungi, entrance into stationary phase is complex as it is accompanied by several differentiation and developmental processes, including the synthesis of pigments, aerial hyphae, anastomoses and sporophores. The regulatory networks that control these processes are still incompletely known. The analysis of the "Impaired in the development of Crippled Growth (IDC)" mutants of the model filamentous ascomycete Podospora anserina has already yielded important information regarding the pathway regulating entrance into stationary phase. Here, the genes affected in two additional IDC mutants are identified as orthologues of the Saccharomyces cerevisiae WHI2 and PSR1 genes, known to regulate stationary phase in this yeast, arguing for a conserved role of these proteins throughout the evolution of ascomycetes. PMID- 27353976 TI - Endothioxopeptides: A conformational overview. AB - Although thionamides would have been first prepared two centuries ago and their chemical and spectroscopic properties extensively investigated, only much more recently (since about 1985) a well deserved but still insufficient attention has been paid to their endothioxopeptide subfamily which nonetheless currently represents a rapidly emerging area of great scientific interest in the broader field of foldameric compounds based on biologically relevant building blocks. After two brief sections offering information on the unfortunately still limited number of endothioxopeptides discovered from natural sources but also on the impressive advancements registered in the last few years in their synthetic methods, this review article outlines the results of a detailed literature survey on the ongoing great, but not systematic, progress related to the conformational consequences generated by incorporating one (or more) thionamide group(s) into a polypeptide chain. Finally, a short discussion of the growing, but still in its infancy, class of the endoselenoxopeptide congeners is also presented. PMID- 27353977 TI - Translational Research and Complexity of Clinical Practice: Issues, Challenges, and Way Forward. PMID- 27353978 TI - Histological Effect of Methotrexate and Folinic Acid on Oral Epithelium of Albino Rats. AB - OBJECTIVE: To determine the extent of damage to oral epithelium caused by high dose methotrexate (HDMTX) and the ameliorating role of folinic acid (FA) on damaging effect of methotrexate. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Anatomy Department of Post Graduate Medical Institute (PGMI), Lahore, from March to September 2013. METHODOLOGY: Forty-two albino rats were randomly allocated to 3 groups: Exp group-I was given HDMTX intramuscularly (I/M) on alternate days, Exp group-II was given both MTX and FA(I/M) on alternate days, and the control group received no intervention. After 16 days, buccal mucosa was excised for histological analysis under light microscope using H & E stains to see the effect of intervention. RESULTS: Exp group-I showed marked reduction in epithelial thickness compared to Exp group-II, and the control (F = 46.44, p < 0.001) had significantly depleted basal layer (F = 6.32, p < 0.004), as well as inflammatory infiltrate with evidence of erosion and ulceration. Exp group-II showed less atrophic changes, a few inflammatory cells, no erosion and ulceration compared to the Exp group-I. Assuming epithelial thickness of control group 100% intact, the Exp group-II was found to have 78% intact and Exp group-I had only 38% thickness intact. Thus FArescued epithelial thickness by 40%. CONCLUSION: Folinic acid considerably saved oral mucosa from the damaging effect of HDMTX, improving quality of life of patients. PMID- 27353979 TI - Bedside Ultrasonography: AUseful Tool for Traumatic Pneumothorax. AB - OBJECTIVE: To compare the diagnostic accuracy of bedside ultrasound and supine chest radiography for the diagnosis of traumatic pneumothorax. STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: PIMS and PAEC General Hospital, Islamabad, from November 2014 to August 2015. METHODOLOGY: Patients coming to emergency departments of the study centres, who had sustained chest injuries, were inducted. Their portable bedside ultrasound and supine chest radiographs were taken for assessing pneumothorax and subsequently CTchest was done for confirmation as gold standard. RESULTS: Based on CTfindings, sensitivity for ultrasonography and chest radiography was found to be 83.33% and 54.76%, respectively and specificity of 100% for both modalities. CONCLUSION: Ultrasound can be used as a useful and suitable adjunct to CTin trauma patients as it is easily available, non-invasive, bedside, easily examined with no radiation risk. PMID- 27353980 TI - Pattern of Altered Lipid Profile in Patients with Subclinical and Clinical Hypothyroidism and its Correlation with Body Mass Index. AB - OBJECTIVE: To compare the lipid profile of the subclinical and clinical hypothyroid patients and to evaluate the correlation between body mass index (BMI) and lipid profile in hypothyroidism. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Islamic International Medical College, Riphah International University, Islamabad, and Citi Laboratory, Rawalpindi, from January to December 2013. METHODOLOGY: The subjects were selected through non probability, purposive sampling. On the basis of thyroid profile, the subjects were divided into 3 groups: euthyroids (n=20), subclinical hypothyroids (n=50), and clinical hypothyroids (n=30). The blood of these subjects was then analyzed for lipid profile. Data was analyzed using SPSS version 18 statistical software. RESULTS: Both hypothyroid groups showed altered lipid profile which was observed to be significantly raised when compared with the euthyroid subjects. Comparison of lipid profile in euthyroid, subclinical, and clinical hypothyroid groups showed significant differences by non-parametric tests (p < 0.05). An assessment of correlation of lipid profile with the BMI was found to be significant (p < 0.01). CONCLUSION: Hypothyroidism causes alteration of lipid profile. Clinical and subclinical hypothyroid patients have altered lipid profile as compared to euthyroids. Thyroid status monitoring is very important, since it can induce changes in lipid profile. Such dyslipidemic status is significant not only for the management of thyroid disorders but also for common diseases like obesity and coronary atherosclerosis in the population. PMID- 27353981 TI - Effect of Lymph Node Retrieval and Ratio on the Long-Term Survival and Recurrence of Colon Cancer. AB - OBJECTIVE: To evaluate the association of lymph node retrieval and ratio with the prognosis of colon cancer. STUDY DESIGN: Acohort study. PLACE AND DURATION OF STUDY: Ninewells Hospital and Medical School, Dundee, UK, from October 2014 to March 2015. METHODOLOGY: Data was collected for adult patients who were diagnosed with primary adenocarcinoma of colon between 2003 and 2008. The follow-up period was 5-year. The data was collected from regional electronic colorectal cancer database. Kaplan-Meier graph was used to calculate and depict overall survival in different groups of patients. RESULTS: There were a total of 370 patients with colon cancer. For Dukes stages Aand B, there was no significant difference in median overall survival for patients with lymph node retrieval (< 12 nodes vs. > 12 nodes). For Dukes stage C (n=147), median survival for patients with lymph node retrieval < 12 nodes was 4 years vs. 4 years for patients with lymph node retrieval > 12 nodes (p = 0.85). Median survival for patients with lymph node ratio (LNR) < 0.125 was 4 years (range 1 - 11) vs. 3 years (range 0 - 11) for patients with LNR > 0.125 (p = 0.14). There was no significant difference in the recurrence rate based on lymph node retrieval (p = 0.87) and LNR (p = 0.97). CONCLUSION: Lymph node retrieval > 12 and reduced LNR < 0.125 had no significant effect on long-term survival and recurrence of colon cancer. PMID- 27353982 TI - Is Surgery Safe in Gallstone-Related Acute Diseases in Elderly Patients? AB - OBJECTIVE: To determinate the safety of the surgical treatment of acute biliary pancreatitis and acute cholecystitis in elderly patients. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of General Surgery, Elazig Training and Research Hospital, Elazig, Turkey, from January 2010 to July 2012. METHODOLOGY: Records of 172 patients with acute complications of biliary calculi, aged over 65 years, were included. Patients were assessed for demographic information, hospitalisation diagnosis, leucocyte count, ASA classification, treatment type, conversion rates, length of hospital stay, morbidity and mortality. Statiscal analyses were performed using the SPSS version 20.0. RESULTS: The sample included 128 females (74.4%) and 44 males (25.6%). Patients' diagnoses included 135 (78.4%) acute cholecystitis and 37 (21.6%) acute pancreatitis. Medical treatment was offered to 113 patients (65.7%). Open cholecystectomy was directly performed in 17 patients (9.9%). Two patients (4.8%) were converted to an open cholecystectomy during surgery, while a laparoscopic cholecystectomy was performed sucessfully on 42 patients (24.4%). Those who underwent surgery were discharged as cured, except for minimal surgical complications. CONCLUSION: Treatment choice in acute gallstone complications in the elderly depends on the patient's general condition, severity of the disease, and ASAscore. Early laparoscopic cholecystectomy is a good option in selected elderly patients with acute cholecystitis and non-severe acute biliary pancreatitis. PMID- 27353983 TI - Paediatric Living Donor Liver Transplantation: ASingle Centre Experience from Pakistan. AB - OBJECTIVE: To determine the outcomes of paediatric living donor liver transplantation (LDLT) recipients from Pakistan in terms of 90-day morbidity and mortality. STUDY DESIGN: Cohort study. PLACE AND DURATION OF STUDY: Shifa International Hospital, Islamabad, Pakistan, between April 2012 and April 2015. METHODOLOGY: All patients in paediatric age group (<= 17 years) who underwent LDLT with a minimum follow-up of 3 months, were included. All grade 2 and above complications on Clavien-Dindo system were included as morbidity. The main outcome measure was 90-day morbidity and mortality. RESULTS: Fourteen paediatric LDLTs were performed. Median age of the recipients was 8.5 years ranging between 6 months and 17 years. Wilson's disease and cryptogenic cirrhosis were the most common etiologies (28.6% each). Acute liver failure was present in 5 (35.7%) patients. Overall 90-day morbidity and mortality was 71.4% and 14.2%; both were attributable to pulmonary infection. No difference was observed in morbidity (21.3% vs. 42.8%, p=0.3) and mortality rates (20% vs. 11%, p=1.0) between patients with acute and chronic liver failure. Estimated 3-year survival was 85%. CONCLUSION: Paediatric LDLT offers a promising treatment option for acute and chronic liver failure. Mortality was attributable to post-transplant pulmonary infections. PMID- 27353984 TI - Interferon Lambda-3 rs12979860 Variants and Response to Pegylated Interferon in Chronic Hepatitis-C Genotype-3. AB - OBJECTIVE: To assess the role of single nucleotide polymorphisms (SNPs) near the interferon lambda-3 (IFNlambda3) (formal IL-28B) gene rs12979860 in predicting sustained virologic response (SVR) in hepatitis-C virus genotype-3 (HCV-3). STUDY DESIGN: Descriptive, analytical study. PLACE AND DURATION OF STUDY: Department of Medicine, The Aga Khan University Hospital, Karachi, from July 2012 to June 2014. METHODOLOGY: Patients with HCV-3 were classified as sustained virologic response (SVR), relapsers and non-responders. SNPrs12979860 was determined by PCR RFLPprotocol. Differences between categorical variables were assessed by chi square or Fisher's exact test, while those between continuous variables were evaluated using the Mann-Whitney U-test. Binary logistic regression analysis by forward conditional method was performed by using significant variables with p values less than 0.05 as the criteria for model inclusion. RESULTS: Out of 115 patients, rs12979860 genotype-CC, CT, TTwas found in 37 (32.2%), 70 (60.9%), and 8 (7%) patients. 72 patients were male with median age of 45 years. Cirrhosis was present in 32 patients. Patients with response failures (no response and relapse, n=36 and 29, respectively) had higher baseline gamma glutamyl transferase (GGT) level (p < 0.001), higher alanine aminotransferase (p=0.027) and cirrhosis (p=0.001) than patients with SVR. Genotype-CC was present in 16/65 in response failures compared to 21/50 who achieved SVR (p=0.048). Rapid virologic response (RVR) (p < 0.001), low GGT(p=0.001) and absence of cirrhosis (p=0.039) were the independent predictive factors for SVR. In patients who could not achieve RVR and in patients with cirrhosis, SVR was seen more in with genotype-CC (p=0.007 and 0.038). CONCLUSION: In patients infected with HCV-3, IFNlambda3 rs12979860, SNPhas less impact on SVR. PMID- 27353985 TI - Microbiological Load of Ethylene Oxide Sterilized Medical Devices and its Elimination by Cobalt 60 Source. AB - OBJECTIVE: To determine the residing microbial flora of ethylene oxide (EtO) sterilized medical devices and optimization of safe dose of gamma radiation (Cobalt 60 source) for the complete elimination of microbial load. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Department of Biotechnology, Lahore College for Women University, Lahore, Pakistan from September 2014 to June 2015. METHODOLOGY: Thirty-six samples of EtO sterilized medical devices of same batch of three different companies were collected for this study. Isolation and enumeration of microbes were done by using different selective and differential media. Gram staining and biochemically characterization by API 20 (Bio Merieux, France) kit was done for identification of the microorganisms. The medical devices having high microbial load were sent to Pakistan Radiation Services (PARAS) for gamma irradiations at 3 different selected doses (20 KGy, 25 KGy, and 30 KGy). RESULTS: Different types of Gram positive bacteria (Staphylococcus epidermidis, Staphylococcus aureus andBacillus subtilis) were isolated from the EtO sterilized samples. Gram negative bacteria and fungi were not detected on these medical devices. Gamma irradiations results showed that 30 KGy was optimized dose for complete elimination of microbial flora on endotracheal, Nelaton, and tracheostomy tubes. CONCLUSION: Gamma radiations (Co 60 source) effectively decontaminate the microbial flora on the equipment previously sterilized by the ethylene oxide gas; and 30 KGy is the optimized dose for all these medical devices. PMID- 27353986 TI - Frequency of Hyperthermia in Acute Ischemic Stroke Patients Visiting a Tertiary Care Hospital. AB - OBJECTIVE: To determine the frequency of hyperthermia in acute ischemic stroke patients visiting a tertiary care hospital in a developing country. STUDY DESIGN: Cross-sectional, observational study. PLACE AND DURATION OF STUDY: Medical Wards of Civil Hospital, Karachi, from January to June 2013. METHODOLOGY: Patients aged >=18 years of either gender with acute ischemic stroke presenting within 24 hours of onset of symptoms were included. Written informed consent was obtained from all participants as well as approval of ethical review committee of the institute. Axillary temperature by mercury thermometer was monitored at the time of admission and after every 6 hours for 3 days. The data was analyzed using SPSS version 17.0 (SPSS Inc., IL, Chicago, USA). RESULTS: Atotal of 106 patients of ischemic stroke were included. The mean age of enrolled participants was 60.1 +/ 9.5 years. Among these, 61 (57.5%) were males and 45 (42.5%) females. Among all patients, 51.9% presented with loss of consciousness, 30.2% with slurred speech, 77.4% with limb weakness, and 9.4% with decrease vision. Atotal of 17 (16%) patients with ischemic stroke developed hyperthermia. When the prevalence of hyperthermia was stratified according to age, among patients of < 60 years of age, 26% developed hyperthermia compared to 7.1% in patients of >=60 years of age (p=0.008). On gender stratification, among male patients, 14.8% developed hyperthermia compared to 17.8% in female patients (p=0.43). CONCLUSION: It is concluded from this study that the frequency of hyperthermia in ischemic stroke was 16% and it should be looked for as it has significant impact on the outcome. The hyperthermia was significantly more common in younger adults as compared to older adults. However, gender had no influence on the prevalence rate of hyperthermia. PMID- 27353987 TI - Central Corneal Thickness and its Relationship to Intra-Ocular and Epidmiological Determinants. AB - OBJECTIVE: To measure central corneal thickness in Pakistani population and determine its relationship to intra-ocular pressure, age, gender and ethnicity. STUDY DESIGN: Cross-sectional observation study. PLACE AND DURATION OF STUDY: Pakistan Institute of Medical Sciences, Islamabad, Pakistan, between December 2013 and February 2015. METHODOLOGY: The right eyes of 1000 cases (496 males and 504 females) were recruited for this study. Inclusion criteria were Pashtun or Punjabi ethnicity, intra-ocular pressure < 22 mmHg, gonioscopically open angles, cup-disk-ratio < 0.5, and age matched normal visual fields. Cases with prior ocular surgery, contact lens use, corneal pathologies, myopia or hypermetropia > +/-3.0 diopters, astigmatism of > +/-1.0 diopters were excluded. Central corneal thickness was measured using a TopCon non-contact specular microscope. Intra ocular pressure was measured using Goldmann applanation tonometer. Frequency distribution, test of significance, and regression analysis was carried out using Statistical Package for Social Sciences version 20.0. RESULTS: Mean age was 47.31 +/-11.78 years. Ethnic composition was 51.6% (n=516) Pashtun and 48.4% (n=484) Punjabi. The mean central corneal thickness was 503.96 (+/-12.47) um, while the mean intra-ocular pressure was 15.61 (+/-2.68) mmHg. Regression analysis showed a significant association between central corneal thickness and intra-ocular pressure (p=0.00) and age (p=0.00). A+/-100 uchange in central corneal thickness was associated with change in IOPof +/-3.30 mmHg, whereas central corneal thickness decreased by 0.12 um per year. No significant association could be established between central corneal thickness and ethnicity (p=0.19). CONCLUSION: Central corneal thickness of the studied races was comparable to non-Caucasians which affects intra-ocular pressure measurements, and decreases with increasing age. No relationship was observed between central corneal thickness and ethnicity or gender. PMID- 27353988 TI - Spectrum of Inherited Metabolic Disorders in Pakistani Children Presenting at a Tertiary Care Centre. AB - OBJECTIVE: To determine the frequency, presentation and outcome of various inherited metabolic diseases in children presenting in a tertiary care hospital, Lahore, Pakistan. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Gastroenterology, Hepatology and Nutrition Department of The Children Hospital and Institute of Child Health, Lahore, from January 2011 to October 2014. METHODOLOGY: All children aged < 14 years with high suspicion of a metabolic disorder were inducted. Routine and radiological investigation were carried out at the study place. Comprehensive diagnostic testing of particular metabolic disorder was sent abroad. Those with a specific metabolic disorder were included in the study while those with normal metabolic work-up were excluded. All data was collected on preformed proforma. RESULTS: Atotal of 239 patients were enrolled. Nineteen different types of inherited metabolic disorders were diagnosed in 180 patients; age ranged from 8 days to 14 years. Consanguinity was positive in 175 (97%) among the parents of the affected children, with previously affected siblings in 64 (35.5%). The most frequent disorders were inherited disorders of carbohydrate metabolism (92, 51%), lipid storage disease (59, 32.7%), organic acidemia and energy defects (18, 10%), amino acid disorder (6, 3.3%), and miscellaneous (4, 2.2%). Fifty-eight (32.2%) presented with acute metabolic crisis, 28 (15.5%) patients presented with early onset liver failure, and 24 (13.3%) with mental retardation. Out of these, 16 (8.8%) expired. CONCLUSION: Glycogen storage disorders being the commonest followed by Gaucher disease and Galactosemia. The associated complications resulted in high morbidity and mortality. PMID- 27353989 TI - Effectiveness of Proprioceptive Neuromuscular Facilitation Techniques as Compared to Traditional Strength Training in Gait Training Among Transtibial Amputees. AB - OBJECTIVE: To determine the effects of proprioceptive neuromuscular facilitation (PNF) techniques as compared with the traditional prosthetic strength training (TPT), in improving ambulatory function in subjects with transtibial amputation. STUDY DESIGN: Randomized control trial. PLACE AND DURATION OF STUDY: Artificial Limb Centre of Fauji Foundation Hospital, Rawalpindi, from July to December 2014. METHODOLOGY: Patients with lower-limb amputation was selected through purposive sampling and randomly assigned into PNF group (n=31) and traditional group (n=32). The baseline and follow-up of 04 weeks treatment session was provided and measurement was noted through the locomotor capabilities index. RESULTS: The locomotor capabilities index abilities had significant difference in both groups. The mean index was 23.93 for PNF and 18.18 for TPT(p > 0.05), and the knee muscle strength was also significantly different (p > 0.05). There was no significant difference in gait parameters. CONCLUSION: Proprioceptive neuromuscular facilitation technique is better in improving the locomotor abilities and knee muscle strength as compared to traditional training. The basic gait parameters have same effect in both groups. PMID- 27353990 TI - Relationship between Unwanted Pregnancy and Health-Related Quality of Life in Pregnant Women. AB - OBJECTIVE: To determine the relationship between unwanted pregnancy and health related quality of life in pregnant women. STUDY DESIGN: Case-control study. PLACE AND DURATION OF STUDY: Department of Community Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran, from October 2013 to July 2014. METHODOLOGY: Of the pregnant women who presented to primary healthcare centers of Kermanshah, Iran to receive prenatal care at 6 - 10 weeks of their pregnancy, those with unwanted pregnancy were selected as cases and those with wanted pregnancy were selected as control group. The selection process was done using multi-stage stratified random sampling. Frequency matching was applied to match the two groups. Quality of life was measured by the SF-36 questionnaire and was compared by the t-test. Relationship power between pregnancy type (wanted or unwanted pregnancy) and impairment of quality of life subscales as the outcome was assessed using odds ratio (OR). RESULTS: Frequency distribution of matched variables was not statistically different between the two studied groups. Mean scores of mental component summary and physical component summary as well as eight subscales (physical functioning, role, bodily pain, general health, vitality, social functioning, role emotional, and mental health) were lower in the unwanted pregnancy group compared to women with wanted pregnancy (p < 0.001). The highest high impairment odds ratio was highest for the mental component summary (MCS) (OR = 9.19; 95% CI = 5.17- 16.32) and vitality subscale (OR = 5.2; 95% CI = 2.89- 9.33). CONCLUSION: Mental health of the pregnant women with unwanted pregnancy is affected more than their physical health. Mental health in women with unwanted pregnancy is 9.19 times more likely to be reduced. Among mental health subscales, vitality (energy/fatigue) showed the highest decrease. PMID- 27353991 TI - Association Between Functional Dyspepsia and Severity of Depression. AB - OBJECTIVE: To determine the association between functional dyspepsia and the severity of depression. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Department of Medicine, King Edward Medical University/Mayo Hospital, Lahore, from September 2012 till January 2013. METHODOLOGY: After taking informed written consent, patients with symptoms of dyspepsia fulfilling the Rome III criteria were included in the study. All patients were evaluated for depression, using Hamilton depression rating scale (HDRS). Upper gastrointestinal endoscopy was done. Fischers' exact test and independent t-test were used for determining significance of association. RESULTS: One hundred and one patients with mean age of 35.81 (+/-14.81) years and male to female ratio of 1.41:1 (54/47) were included. Predominant symptoms were early satiety (72.3%), epigastric pain (65.3%), bloating (49.5%), postprandial fullness (40.6%), and regurgitation (40.6%). Alarm symptoms were positive in 44 (43.6%) patients. Dyspepsia were classified as epigastric pain syndrome (EPS, 69.3%), and postprandial distress syndrome (PDS, 30.7%). Significantly more females had PDS (p=0.04), with positive endoscopic findings in EPS (p=0.03). Positive endoscopic findings noted were esophagitis in 21.8%, and gastritis in 48.5% patients. All patients except one had depression, mild in 22.8%, moderate in 33.7%, severe in 31.7%, and very severe in 10.9% patients. Severe depression was seen in 32 (45.7%) patients with EPS and PDS; whereas very severe depression was in 11 (15.7%) patients of EPS, while 11 (35.4%) patients of PDS had severe depression but the difference was not significant. CONCLUSION: Functional dyspepsia is associated with depression, while positive endoscopic findings are more likely in patients with EPS. Very severe depression was only seen with epigastric pain syndrome. PMID- 27353992 TI - Snake-bite-induced Acute Kidney Injury. AB - OBJECTIVE: To describe the clinical spectrum and outcome of patients presenting to a tertiary care kidney center, developing acute kidney injury (AKI) after snake-bite. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Nephrology Department, Sindh Institute of Urology and Transplantation (SIUT), Karachi, from January 1990 to December 2014. METHODOLOGY: All patients coming to SIUTidentified as having AKI after snake-bite during the study period were included. AKI was defined according to RIFLE criteria with sudden rise in creatinine or decline in urine output or both. Demographics, clinical presentation, laboratory profile, and final outcome was noted. RESULTS: During the studied period, 115 cases of AKI, secondary to snake-bite, were registered at this institution. Median age of patients was 35.92 +/-15.04 (range: 6 - 70) years and male to female ratio was 1.6:1. Time from bite and referral to this hospital ranged from 2 to 28 days (mean: 8.77 +/-5.58 days). Oligo-anuria was the most common presentation, being found in 98 (93.90%) patients. Bleeding diathesis was reported in 75 (65.21%) patients on presentation. All patients had normal sized, non-obstructed kidneys on ultrasonography, with no previous comorbids. Renal replacement therapy (RRT) was required in 106 (92.17%) patients. Complete recovery was seen in 59 (51.30%), while 15 (13.04%) patients expired during acute phase of illness, 4 (3.47%) developed CKD, 11 (9.56%) required dialysis beyond 90 days, and 26 (22.60%) were lost to long-term follow-up. CONCLUSION: Snake-bite, leading to multiple complications including renal failure and death, is a major health issue in tropical countries. Late referral of these patients to specialized centres results in undesirable outcome. PMID- 27353993 TI - Imaging Guided Breast Interventions. AB - Breast imaging is a developing field, with new and upcoming innovations, decreasing the morbidity and mortality related to breast pathologies with main emphasis on breast cancer. Breast imaging has an essential role in the detection and management of breast disease. It includes a multimodality approach, i.e. mammography, ultrasound, magnetic resonance imaging, nuclear medicine techniques and interventional procedures, done for the diagnosis and definitive management of breast abnormalities. The range of methods to perform biopsy of a suspicious breast lesion found on imaging has also increased markedly from the 1990s with hi technological progress in surgical as well as percutaneous breast biopsy methods. The image guided percutaneous breast biopsy procedures cause minimal breast scarring, save time, and relieve the patient of the anxiety of going to the operation theatre. The aim of this review was to describe and discuss the different image guided breast biopsy techniques presently employed along with the indications, contraindication, merits and demerits of each method. PMID- 27353994 TI - A Cross-Sectional Analysis of Use of Information Technology by Selected Students of Health Colleges of a Saudi University. AB - OBJECTIVE: To determine the use of information technology (IT) among students of Medicine, Dentistry, and Pharmacy in Prince Sattam Bin AbdulAziz University, Al Khraj, Saudi Arabia (PSAU). STUDY DESIGN: Across-sectional survey. PLACE AND DURATION OF STUDY: From September 2014 to January, 2015. METHODOLOGY: Aclose ended questionnaire consisting of 30 multiple choice questions (MCQs) was distributed to the students. The questions were related to their access to computers, skills and training, computer activities, and internet access. Data analyses and descriptive analyses for various variables were performed using SPSS version 17.0. RESULTS: An overall response rate of 84.9% (488 out of 575) was obtained. All of the students (100%) had an access to the computers. Most of the students (61.9%) used computers for academic purposes. Amajority of the students (74.4%) preferred the use of powerpoint presentations aided by marker-and-board method for teaching. For communication from the colleges, 62.9% of the respondents preferred it through the email; 100% of the students had an email account. All of the students (100%) used internet; 83.1% considered the information as accurate. The internet was used by 47.6% of the students for seeking the medical information. CONCLUSION: All of the students had an access to ITand used it for their educational purposes. PMID- 27353995 TI - Modified Quilting Sutures: ANew Technique for Hematoma and Abscess of Nasal Septum. AB - This study aimed to analyze the results of a modified continuous quilting sutures technique in a series of patients presenting with hematoma and/or abscess of nasal septum (HANS). Only patients with a confirmed diagnosis of HANS without co morbid conditions (which could predispose to a bleeding tendency), were selected. Following incision and drainage, nasal septal flaps were coapted by applying continuous quilting sutures only. The success rate of this technique in terms of recurrence requiring re-exploration and drainage was 100%. Quilting sutures were generally well tolerated with few complaints. Saddle deformity was the most obvious complication of HANS, seen with septal abscess. Quilting sutures can be considered as an alternative treatment option for HANS. The modified technique employed in this study demonstrated impressive results and avoided the morbidity of nasal packing with fewer complications. PMID- 27353996 TI - Percutaneous Closure of Patent Ductus Arteriosus Under Echocardiographic Guidance. AB - Percutaneous closure of patent ductus arteriosus (PDA) is done in the cardiac catheterization laboratory, usually under fluoroscopic and angiographic guidance. The aortogram is used for assessing PDAsize and shape the pre-device implantation. Additionally, post-device aortograms are applied for the assessment of device position, profile and residual shunt. Angiograms expose patient to radiation and possible untoward effects of contrast media. Recently, transthoracic echocardiography has been utilized to guide in PDAclosure to avoid radiation exposure as well as contrast material. On two occasions, we were obligated by special circumstances to close the PDAunder echocardiography guidance. First case was a 6-month baby girl with mild signs of heart failure having moderate size PDA. She underwent device closure under transthoracic echocardiogram as the angiographic system had stopped working during the procedure. Second case was a 6-year girl, weighting 16-kg with chronic renal failure. She had moderate size PDAclosed by device under transthoracic echocardiographic, guidance avoiding the use of contrast agent due to chronic renal failure. PMID- 27353997 TI - Coexistence of Celiac and Crohn's Disease in a Patient Presenting with Chronic Diarrhea. AB - Celiac disease (CD) is one of the most common causes of malabsorption. It is an immune-mediated disease manifested by diarrhea, steatorrhea, flatulence, and weight loss, caused by ingestion of gluten containing diets. The disease has typical small intestinal biopsy features of villous atrophy, crypt hyperplasia, and intense inflammation of the mucosal layer. The disease is rarely associated with Crohn's disease (CRD). Studies on the impact of CD on the natural history of inflammatory bowel disease (IBD) have shown that the natural course of CRD is not influenced by coexistent CD. We report a case of 54-year female who presented with diarrhea and weight loss. On initial evaluation, CD was diagnosed, and responded to gluten-free diet (GFD). Later on, she developed joint pains and her diarrhea recurred. Further evaluation revealed coexistence of CRD. The treatment of CRD was also initiated and this led to marked improvement in the symptoms of the patient. PMID- 27353998 TI - Hemolytic Anemia and Heart Failure Caused by Anti-C and Anti-E Immunization. AB - Many different blood group systems, such as Rh, ABO, Kell, Kidd, Duffy, MNS, have been reported as causes of hemolytic disease of the newborn. Hemolysis due to minor blood group incompatibility in the fetus or newborn has been determined in isolated case reports. Here, we report a case of a patient who had received red cell transfusion due to severe Rh c and E incompatibility, leading to hemolytic anemia with heart failure. The mother and the baby were grouped B and B, respectively, both being positive for RhD antigen. The baby's blood group type was C+, c+, E+, e+, K-, while her mother's blood group type was C+, c-, E-, e+, K . Our patient was diagnosed as Rh c and E incompatibility, leading to the hemolytic anemia. Minor blood group incompatibility should be considered in infants with prolonged jaundice and severe anemia, leading to heart failure. PMID- 27353999 TI - Diagnostic Accuracy of Anti-Endomysial Antibody in Celiac Disease. AB - The objective of the study was to determine the diagnostic accuracy of anti-EMA antibody in comparison to histopathological findings in patients suspected of CD. This cross-sectional study was conducted at Gastroenterology Department, Fatima Memorial Hospital, Lahore, from March to October 2014. One hundred and twenty-one patients aged between 5 - 60 years of either gender were recruited in the study. Every patient went through serological testing and biopsy specimens were obtained from second part of the duodenum. Histopathological evaluation was done according to the Modified Marsh classification. The overall sensitivity of anti-EMAcame out to be 85.7% which varied with the histological lesions being 75.0%, 83.3%, and 100% for Marsh IIIA, IIIB and IIIC, respectively. Although anti-EMAhas high sensitivity but serological tests as a sole mean of diagnosis are currently unable to replace the biopsy. PMID- 27354000 TI - Statistical Analysis of Factors Affecting Child Mortality in Pakistan. AB - Child mortality is a composite indicator reflecting economic, social, environmental, healthcare services, and their delivery situation in a country. Globally, Pakistan has the third highest burden of fetal, maternal, and child mortality. Factors affecting child mortality in Pakistan are investigated by using Binary Logistic Regression Analysis. Region, education of mother, birth order, preceding birth interval (the period between the previous child birth and the index child birth), size of child at birth, and breastfeeding and family size were found to be significantly important with child mortality in Pakistan. Child mortality decreased as level of mother's education, preceding birth interval, size of child at birth, and family size increased. Child mortality was found to be significantly higher in Balochistan as compared to other regions. Child mortality was low for low birth orders. Child survival was significantly higher for children who were breastfed as compared to those who were not. PMID- 27354001 TI - Successful Treatment of Haemoglobinopathy Associated Chronic Leg Ulcer with Platelet Rich Plasma. PMID- 27354002 TI - Acute Rheumatic Fever Carditis Presenting as Fever of Unknown Origin. PMID- 27354003 TI - Thoracic Mass in an Immune-Competent Child. PMID- 27354004 TI - Use of Video Laryngoscopy for Rapid Sequence Induction. PMID- 27354005 TI - Cyclophilin A protects mice against infection by influenza A virus. AB - Our previous studies indicate that Cyclophilin A (CypA) impairs the replication of influenza A virus in vitro. To further evaluate the antiviral functions of CypA and explore its mechanism, transgenic mice with overexpression of CypA by two specific promoters with SPC (CypA-SPC) or CMV (CypA-CMV) were developed. After challenge with the A/WSN/33(H1N1) influenza virus, CypA-SPC and CypA-CMV transgenic mice displayed nearly 2.5- and 3.8-fold stronger disease resistance to virus infection, respectively, compared to wild-type animals. Virus replication, pathological lesions and inflammatory cytokines were substantially reduced in both lines of transgenic mice. In addition, after infection there was an upregulation of genes associated with cell migration, immune function, and organ development; and a downregulation of genes associated with the positive regulation of immune cells and apoptosis in the peritoneal macrophages of CypA overexpressing transgenic mice (CypA+). These results indicate that CypA is a key modulator of influenza virus resistance in mice, and that CypA+ mice constitutes an important model to study the roles of CypA in the regulation of immune responses and infections. PMID- 27354006 TI - Multifucosylated Alpha-1-acid Glycoprotein as a Novel Marker for Hepatocellular Carcinoma. AB - High-sensitivity and -specificity diagnostic techniques to detect early-stage hepatocellular carcinoma (HCC) are in high demand. Screening with serum HCC markers, such as alpha-fetoprotein, is not practical because they possess poor sensitivity and specificity. As such, we focused on glycan alterations of glycoproteins found in patient sera in an attempt to discover novel HCC markers that are more specific and sensitive than current HCC markers. Sera from 42 HCC patients and 80 controls, composed of 27 chronic hepatitis B patients, 26 chronic hepatitis C patients, and 27 healthy volunteers, were analyzed in this study. Glycopeptides obtained from serum proteins by trypsin digestion were enriched by ultrafiltration and Aleuria aurantia lectin-based affinity chromatography, followed by analysis using liquid chromatography time-of-flight mass spectrometry. The data were analyzed by our newly developed software, which calculates peak intensities and positions (m/z and elution time), aligns all sample peaks, and integrates all data into a single table. HCC markers were extracted from more than 30 000 detected glycopeptide peaks by t test, mean-fold change, and ROC analyses. As a result, we revealed that alpha-1-acid glycoprotein with multifucosylated tetraantennary N-glycans was significantly elevated in HCC patients, whereas the single fucosylated derivative was not. PMID- 27354007 TI - Role of IL-10-producing regulatory B cells in modulating T-helper cell immune responses during silica-induced lung inflammation and fibrosis. AB - Silicosis is characterized by chronic lung inflammation and fibrosis, which are seriously harmful to human health. Previous research demonstrated that uncontrolled T-helper (Th) cell immune responses were involved in the pathogenesis of silicosis. Lymphocytes also are reported to have important roles. Existing studies on lymphocyte regulation of Th immune responses were limited to T cells, such as the regulatory T (Treg) cell, which could negatively regulate inflammation and promote the process of silicosis. However, other regulatory subsets in silicosis have not been investigated in detail, and the mechanism of immune homeostasis modulation needs further exploration. Another regulatory lymphocyte, the regulatory B cell, has recently drawn increasing attention. In this study, we comprehensively showed the role of IL-10-producing regulatory B cell (B10) in a silicosis model of mice. B10 was inducible by silica instillation. Insufficient B10 amplified inflammation and attenuated lung fibrosis by promoting the Th1 immune response. Insufficient B10 clearly inhibited Treg and decreased the level of IL-10. Our study indicated that B10 could control lung inflammation and exacerbate lung fibrosis by inhibiting Th1 response and modulating the Th balance. The regulatory function of B10 could be associated with Treg induction and IL-10 secretion. PMID- 27354009 TI - Implementation of a repeated fed-batch process for the production of chitin glucan complex by Komagataella pastoris. AB - The yeast Komagataella pastoris was cultivated under different fed-batch strategies for the production of chitin-glucan complex (CGC), a co-polymer of chitin and beta-glucan. The tested fed-batch strategies included DO-stat mode, predefined feeding profile and repeated fed-batch operation. Although high cell dry mass and high CGC production were obtained under the tested DO-stat strategy in a 94h cultivation (159 and 29g/L, respectively), the overall biomass and CGC productivities were low (41 and 7.4g/Lday, respectively). Cultivation with a predefined profile significantly improved both biomass and CGC volumetric productivity (87 and 10.8g/Lday, respectively). Hence, this strategy was used to implement a repeated fed-batch process comprising 7 consecutive cycles. A daily production of 119-126g/L of biomass with a CGC content of 11-16wt% was obtained, thus proving this cultivation strategy is adequate to reach a high CGC productivity that ranged between 11 and 18g/Lday. The process was stable and reproducible in terms of CGC productivity and polymer composition, making it a promising strategy for further process development. PMID- 27354008 TI - Cellular responses to HSV-1 infection are linked to specific types of alterations in the host transcriptome. AB - Pathogen invasion triggers a number of cellular responses and alters the host transcriptome. Here we report that the type of changes to cellular transcriptome is related to the type of cellular functions affected by lytic infection of Herpes Simplex Virus type I in Human primary fibroblasts. Specifically, genes involved in stress responses and nuclear transport exhibited mostly changes in alternative polyadenylation (APA), cell cycle genes showed mostly alternative splicing (AS) changes, while genes in neurogenesis, rarely underwent these changes. Transcriptome wide, the infection resulted in 1,032 cases of AS, 161 incidences of APA, 1,827 events of isoform changes, and up regulation of 596 genes and down regulations of 61 genes compared to uninfected cells. Thus, these findings provided important and specific links between cellular responses to HSV 1 infection and the type of alterations to the host transcriptome, highlighting important roles of RNA processing in virus-host interactions. PMID- 27354010 TI - Severe, persistent, and fatal T-cell immunodeficiency following therapy for infantile leukemia. AB - We describe five cases of children who completed chemotherapy for infantile acute lymphoblastic leukemia (ALL) and soon after were diagnosed with severe T-cell, non-HIV immunodeficiency, with varying B-cell and NK-cell depletion. There was near absence of CD3(+) , CD4(+) , and CD8(+) cells. All patients developed multiple, primarily opportunistic infections. Unfortunately, four patients died, although one was successfully treated by hematopoietic stem cell transplantation. These immunodeficiencies appeared to be secondary to intensive infant ALL chemotherapy. Our report highlights the importance of the early consideration of this life-threatening immune complication in patients who received chemotherapy for infantile ALL. PMID- 27354011 TI - Use of MALDI-TOF to detect colonized vascular catheter tips after 6 and 12h of incubation. AB - We analyzed by MALDI-TOF MS 80 catheter tips after 6h and 12h of incubation and the sensitivity of each incubation period for the identification of colonization and C-RBSI was, respectively, 9.5%-NA and 42.9%-28.6%. Despite MALDI-TOF MS cannot be used to predict catheter colonization, it may rule out C-RBSI. PMID- 27354012 TI - Using multi-criteria decision making for selection of the optimal strategy for municipal solid waste management. AB - Multi-criteria decision making (MCDM) is a relatively new tool for decision makers who deal with numerous and often contradictory factors during their decision making process. This paper presents a procedure to choose the optimal municipal solid waste (MSW) management system for the area of the city of Kragujevac (Republic of Serbia) based on the MCDM method. Two methods of multiple attribute decision making, i.e. SAW (simple additive weighting method) and TOPSIS (technique for order preference by similarity to ideal solution), respectively, were used to compare the proposed waste management strategies (WMS). Each of the created strategies was simulated using the software package IWM2. Total values for eight chosen parameters were calculated for all the strategies. Contribution of each of the six waste treatment options was valorized. The SAW analysis was used to obtain the sum characteristics for all the waste management treatment strategies and they were ranked accordingly. The TOPSIS method was used to calculate the relative closeness factors to the ideal solution for all the alternatives. Then, the proposed strategies were ranked in form of tables and diagrams obtained based on both MCDM methods. As shown in this paper, the results were in good agreement, which additionally confirmed and facilitated the choice of the optimal MSW management strategy. PMID- 27354013 TI - Treatment of a mud pit by bioremediation. AB - The mud generated from oil and natural gas drilling, presents a considerable ecological problem. There are still insufficient remedies for the removal and minimization of these very stable emulsions. Existing technologies that are in use, more or less successfully, treat about 20% of generated waste drilling mud, while the rest is temporarily deposited in so-called mud pits. This study investigated in situ bioremediation of a mud pit. The bioremediation technology used in this case was based on the use of naturally occurring microorganisms, isolated from the contaminated site, which were capable of using the contaminating substances as nutrients. The bioremediation was stimulated through repeated inoculation with a zymogenous microbial consortium, along with mixing, watering and biostimulation. Application of these bioremediation techniques reduced the concentration of total petroleum hydrocarbons from 32.2 to 1.5 g kg( 1) (95% degradation) during six months of treatment. PMID- 27354014 TI - Quantitative option analysis for implementation and management of landfills. AB - The selection of the most feasible strategy for implementation of landfills is a challenging step. Potential implementation options of landfills cover a wide range, from conventional construction contracts to the concessions. Montenegro, seeking to improve the efficiency of the public services while maintaining affordability, was considering privatisation as a way to reduce public spending on service provision. In this study, to determine the most feasible model for construction and operation of a regional landfill, a quantitative risk analysis was implemented with four steps: (i) development of a global risk matrix; (ii) assignment of qualitative probabilities of occurrences and magnitude of impacts; (iii) determination of the risks to be mitigated, monitored, controlled or ignored; (iv) reduction of the main risk elements; and (v) incorporation of quantitative estimates of probability of occurrence and expected impact for each risk element in the reduced risk matrix. The evaluated scenarios were: (i) construction and operation of the regional landfill by the public sector; (ii) construction and operation of the landfill by private sector and transfer of the ownership to the public sector after a pre-defined period; and (iii) operation of the landfill by the private sector, without ownership. The quantitative risk assessment concluded that introduction of a public private partnership is not the most feasible option, unlike the common belief in several public institutions in developing countries. A management contract for the first years of operation was advised to be implemented, after which, a long term operating contract may follow. PMID- 27354015 TI - Waste management under a life cycle approach as a tool for a circular economy in the canned anchovy industry. AB - The anchovy canning industry has high importance in the Cantabria Region (North Spain) from economic, social and touristic points of view. The Cantabrian canned anchovy is world-renowned owing to its handmade and traditional manufacture. The canning process generates huge amounts of several food wastes, whose suitable management can contribute to benefits for both the environment and the economy, closing the loop of the product life cycle. Life cycle assessment methodology was used in this work to assess the environmental performance of two waste management alternatives: Head and spine valorisation to produce fishmeal and fish oil; and anchovy meat valorisation to produce anchovy paste. Fuel oil production has been a hotspot of the valorisation of heads and spines, so several improvements should be applied. With respect to anchovy meat valorisation, the production of polypropylene and glass for packaging was the least environmentally friendly aspect of the process. Furthermore, the environmental characterisation of anchovy waste valorisation was compared with incineration and landfilling alternatives. In both cases, the valorisation management options were the best owing to the avoided burdens associated with the processes. Therefore, it is possible to contribute to the circular economy in the Cantabrian canned anchovy industry. PMID- 27354016 TI - Did we choose the best one? A new site selection approach based on exposure and uptake potential for waste incineration. AB - Ecological problems arising after the construction and operation of a waste incineration plant generally originate from incorrect decisions made during the selection of the location of the plant. The main objective of this study is to investigate how the selection method for the location of a new municipal waste incineration plant can be improved by using a dispersion modelling approach supported by geographical information systems and multi-criteria decision analysis. Considering this aim, the appropriateness of the current location of an existent plant was assessed by applying a pollution dispersion model. Using this procedure, the site ranking for a total of 90 candidate locations and the site of the existing incinerator were determined by a new location selection practice and the current place of the plant was evaluated by ANOVA and Tukey tests. This ranking, made without the use of modelling approaches, was re-evaluated based on the modelling of various variables, including the concentration of pollutants, population and population density, demography, temporality of meteorological data, pollutant type, risk formation type by CALPUFF and re-ranking the results. The findings clearly indicate the impropriety of the location of the current plant, as the pollution distribution model showed that its location was the fourth-worst choice among 91 possibilities. It was concluded that the location selection procedures for waste incinerators should benefit from the improvements obtained by the articulation of pollution dispersion studies combined with the population density data to obtain the most suitable location. PMID- 27354017 TI - Results of fibre and toner flotation depending on oleic acid dosage. AB - The literature was reviewed with respect to deinking flotation methods with toner samples, specifically emphasizing the speciation of copy machine and laser printing, which produce an increasing quantity of paper that is difficult to recycle. Speciation here refers to the physical-chemical characteristics of the toner, which change because of the polymerization (fusion) and oxidation process, due to exposure to heat, light and oxygen (air) during the printing process. To simulate the deinking flotation, after the ideal disintegration process, samples of toner were prepared in order to provide free toner particles. Synthetic toner has iron content and the same physical-chemical features as free disintegrated printed toner particles.We report the toner (I) and fibre (Y) recovery and the brightness (B) of laboratory filter pads formed of deinked product as deinking efficiencies. The application of oleic acid as the collector in the flotation stage gives a better flotation recovery in alkaline than in acidic conditions. The highest brightness (BF = 93.66%) and flotation recoveries (I = 90, Y = 92.82%) were achieved during testing at an oleic acid concentration of 3.38.10( 6) mol l(-1), which is the lowest dose used. This makes the use of oleic acid economical and environmentally friendly. PMID- 27354018 TI - 2016 ACC/AHA Clinical Performance and Quality Measures for Adults With Atrial Fibrillation or Atrial Flutter: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. PMID- 27354019 TI - Grey matter atrophy is associated with disability increase in natalizumab-treated patients. AB - BACKGROUND: Brain volume loss (BVL) is a key outcome in multiple sclerosis (MS) trials. Natalizumab is highly effective on inflammation with moderate impact on atrophy. OBJECTIVE: To explore BVL in patients receiving natalizumab with an emphasis on grey matter (GM). METHODS: We performed a retrospective post hoc analysis of BVL in 38 patients receiving natalizumab for 3 years using longitudinal voxel-based morphometry (VBM) and FreeSurfer. RESULTS: Significant BVL was observed during first year: brain parenchymal fraction (BPF): -1.12% ( p < 0.001); white matter fraction (WMF): -0.9% ( p = 0.001); grey matter fraction (GMF): -1.28% ( p = 0.002). GM loss was found using VBM in bilateral cerebellum, cingulum, left > right fronto-parietal cortex, right > left hippocampus and left caudate. FreeSurfer showed significant volume losses in subcortical GM, brainstem and cerebellum, and cortical thinning in the left insula. In the second year, only WMF decrease (-0.6%; p = 0.015) was observed with no VBM changes, although FreeSurfer detected significant volume loss in thalamus, hippocampus and cerebellum. Baseline gadolinium enhancement influenced WMF and BPF changes during the first year, but not GMF. Patients with confirmed Expanded Disability Status Scale (EDSS) worsening at 3 years had lower baseline GMF and left thalamus volume and greater BVL over follow-up. CONCLUSION: BVL develops mainly during the first year of natalizumab therapy. GM changes are independent of baseline inflammation and correlate with disability. PMID- 27354020 TI - Working memory network dysfunction in relapse-onset multiple sclerosis phenotypes: A clinical-imaging evaluation. AB - OBJECTIVES: We investigated clinical, behavioural and functional magnetic resonance imaging (fMRI) correlates of working memory load in relapse-onset multiple sclerosis (MS) patients. METHODS: In total, 12 clinically isolated syndromes (CIS) patients at risk of MS, 38 relapsing-remitting multiple sclerosis (RRMS), 22 secondary progressive multiple sclerosis (SPMS) and 24 healthy controls (HC) performed an N-back fMRI task. Correlations between fMRI abnormalities and clinico-behavioural and structural magnetic resonance imaging (MRI) measures were assessed. RESULTS: Participants activated brain regions of the working memory network, especially in fronto-parietal lobes and cerebellum, and deactivated areas of the default mode network (DMN). During the N-back load contrast, compared to HC, the three groups of MS patients had a common pattern of decreased activation of the right superior parietal lobule, left inferior parietal lobule and left middle frontal gyrus. Areas specifically more active in CIS patients compared to the other study groups were found in the left medial superior frontal gyrus and right anterior cingulate cortex, whereas SPMS patients selectively activated the left parahippocampal gyrus and left superior temporal pole (STP). Worse accuracy and global cognitive scores correlated with increased STP activation. CONCLUSION: Load-dependent alterations of working memory network recruitment occur in MS. Frontal hyperactivation is maintained in CIS and lost in SPMS. Abnormal recruitment of DMN areas is related to worse cognitive and behavioural outcomes. PMID- 27354021 TI - A phase I study of CD25/regulatory T-cell-depleted donor lymphocyte infusion for relapse after allogeneic stem cell transplantation. AB - Donor lymphocyte infusions are used to treat relapse after allogeneic hematopoietic stem cell transplantation, but responses are inadequate. In addition to effector cells, infusions contain CD25+ regulatory T cells (Treg) that may suppress graft-versus-tumor responses. We undertook a phase I study of donor lymphocyte infusions depleted of CD25+ T cells in patients with hematologic malignancies who had relapsed after transplantation. Twenty-one subjects received CD25/Treg-depleted infusions following removal of CD25+ cells using antibody conjugated magnetic beads. Sixteen subjects received prior cytoreductive therapy. Four were in complete remission at the time of infusion. Two dose levels were administered: 1*107 (n=6) and 3*107 CD3+ cells/kg (n=15). A median 2.3 log depletion of CD4+CD25+FOXP3+ Treg was achieved. Seven subjects (33%) developed clinically significant graft-versus-host disease by 1 year, including one patient who died. At dose level 1, five subjects had progressive disease and one had stable disease. At dose level 2, nine subjects (60%) achieved or maintained responses (8 complete responses, 1 partial response), including seven with active disease at the time of infusion. A shorter period between relapse and infusion was associated with response at dose level 2 (P=0.016). The 1-year survival rate was 53% among patients treated with dose level 2. Four of eight subjects with acute myeloid leukemia remained in remission at 1 year. When compared to unmodified donor lymphocyte infusions in 14 contemporaneous patients meeting study eligibility, CD25/Treg depletion was associated with a better response rate and improved event-free survival. Circulating naive and central memory CD4+ T cells increased after CD25/Treg-depleted infusion, but no immunophenotypic signature for response was noted. CD25/Treg-depleted donor infusion appears feasible and capable of inducing graft-versus-tumor responses without excessive graft-versus-host disease. (ClinicalTrials.gov NCT#00675831). PMID- 27354022 TI - Discrepancies of applying primary myelofibrosis prognostic scores for patients with post polycythemia vera/essential thrombocytosis myelofibrosis. PMID- 27354023 TI - Donor and recipient sex in allogeneic stem cell transplantation: what really matters. AB - We investigated whether and how recipient-donor sex affects transplantation outcomes of 11,797 patients transplanted between 2008 and 2010. Thirty-seven percent were male recipients with male donors, 21% male recipients with female donors, 25% female recipients with male donors, and 17% female recipients with female donors. In multivariable analyses, male recipients had inferior overall survival and progression-free survival compared to females regardless of donor sex, with an 11% relative increase in the hazard of death (P<0.0001) and a 10% relative increase in the hazard of death or relapse (P<0.0001). The detrimental effect of male recipients varied by donor sex. For male recipients with male donors, there was a 12% relative increase in the subdistribution hazard of relapse compared with female recipients with male donors (P=0.0036) and male recipients with female donors (P=0.0037). For male recipients with female donors, there was a 19% relative increase in the subdistribution hazard of non-relapse mortality compared with male recipients with male donors (P<0.0001) and a 22% relative increase compared with female recipients with male donors (P=0.0003). In addition, male recipients with female donors showed a 21% relative increase in the subdistribution hazard of chronic graft-versus-host disease (P<0.0001) compared with female recipients with male donors. Donor sex had no effect on outcomes for female recipients. Transplantation of grafts from male and female donors was associated with inferior overall survival and progression-free survival in male recipients with differing patterns of failure. Recipient sex is an important prognostic factor independent of donor sex. PMID- 27354025 TI - [The burial of a scientific finding]. PMID- 27354024 TI - Non-Hodgkin lymphoma in the developing world: review of 4539 cases from the International Non-Hodgkin Lymphoma Classification Project. AB - The distribution of non-Hodgkin lymphoma subtypes varies around the world, but a large systematic comparative study has never been done. In this study, we evaluated the clinical features and relative frequencies of non-Hodgkin lymphoma subtypes in five developing regions of the world and compared the findings to the developed world. Five expert hematopathologists classified 4848 consecutive cases of lymphoma from 26 centers in 24 countries using the World Health Organization classification, and 4539 (93.6%) were confirmed to be non-Hodgkin lymphoma, with a significantly greater number of males than females in the developing regions compared to the developed world (P<0.05). The median age at diagnosis was significantly lower for both low- and high-grade B-cell lymphoma in the developing regions. The developing regions had a significantly lower frequency of B-cell lymphoma (86.6%) and a higher frequency of T- and natural killer-cell lymphoma (13.4%) compared to the developed world (90.7% and 9.3%, respectively). Also, the developing regions had significantly more cases of high-grade B-cell lymphoma (59.6%) and fewer cases of low-grade B-cell lymphoma (22.7%) compared to the developed world (39.2% and 32.7%, respectively). Among the B-cell lymphomas, diffuse large B-cell lymphoma was the most common subtype (42.5%) in the developing regions. Burkitt lymphoma (2.2%), precursor B- and T-lymphoblastic leukemia/lymphoma (1.1% and 2.9%, respectively) and extranodal natural killer/T cell lymphoma (2.2%) were also significantly increased in the developing regions. These findings suggest that differences in etiologic and host risk factors are likely responsible, and more detailed epidemiological studies are needed to better understand these differences. PMID- 27354026 TI - Marine reserves lag behind wilderness in the conservation of key functional roles. AB - Although marine reserves represent one of the most effective management responses to human impacts, their capacity to sustain the same diversity of species, functional roles and biomass of reef fishes as wilderness areas remains questionable, in particular in regions with deep and long-lasting human footprints. Here we show that fish functional diversity and biomass of top predators are significantly higher on coral reefs located at more than 20 h travel time from the main market compared with even the oldest (38 years old), largest (17,500 ha) and most restrictive (no entry) marine reserve in New Caledonia (South-Western Pacific). We further demonstrate that wilderness areas support unique ecological values with no equivalency as one gets closer to humans, even in large and well-managed marine reserves. Wilderness areas may therefore serve as benchmarks for management effectiveness and act as the last refuges for the most vulnerable functional roles. PMID- 27354028 TI - Corrigendum to "Characterization of the fatty acid composition of lamb commercially available in northern Spain: Emphasis on the trans-18:1 and CLA content and profile" [Meat Science 117 (2016) 108-116]. PMID- 27354027 TI - Extrinsic allospecific signals of hematopoietic origin dictate iNKT cell lineage fate decisions during development. AB - Invariant NKT (iNKT) cells are critical to the maintenance of tolerance toward alloantigens encountered during postnatal life pointing to the existence of a process for self-education. However, the impact of developmentally encountered alloantigens in shaping the phenotype and function of iNKT cells has not been described. To better understand this process, the current report examined naive iNKT cells as they matured in an allogeneic environment. Following the prenatal transfer of fetal hematopoietic cells between age-matched allogeneic murine fetuses, cell-extrinsic signals appeared to dictate allospecific patterns of Ly49 receptor expression and lineage diversity in developing iNKT cells. Regulation for this process arose from cells of hematopoietic origin requiring only rare exposure to facilitate broad changes in developing iNKT cells. These findings highlight surprisingly asymmetric allospecific alterations in iNKT cells as they develop and mature in an allogeneic environment and establish a new paradigm for study of the self-education of iNKT cells. PMID- 27354029 TI - The evolution of research on occlusion and brain function. PMID- 27354030 TI - Mandibular movement during sleep bruxism associated with current tooth attrition. AB - PATIENT: Observation of attrition patterns suggests that mandibular movement in sleep bruxism (SB) may be associated with current tooth attrition. The aim of this study was to confirm this phenomenon by investigating mandibular movement and masseter muscle activity. The subject was a healthy 21-year-old Japanese male. We recorded biological signals including mandibular movement and masseter electromyograms (EMGs) with a polysomnograph. Based on the EMG using Okura's criteria, SB events were classified into clenching, grinding and mixed types according to mandibular movement criteria. The close-open mandibular movement cycles (CO-cycles) during grinding and mixed type events were selected based on mandibular movement trajectories. DISCUSSION: Fifty-eight CO-cycles were selected in seven grinding and three mixed types. We found that SB mandibular movements associated with current tooth attrition. Excessive lateral movements (ELM) beyond the canine edge-to-edge position were observed in the closing (10.3%) and opening (13.8%) phases of the CO-cycle. Total masseter muscle activity was significantly higher during voluntary grinding (VGR) than during CO-cycle including ELM (working side: P=0.036, balancing side: P=0.025). However, in the middle and late parts of the opening phase, working side masseter muscle activity was significantly higher during CO-cycle including ELM than during VGR (P=0.012). In the early part of the closing phase, balancing side masseter muscle activity was significantly higher during CO-cycle including ELM than during VGR (P=0.017). CONCLUSION: These findings suggest that excessive forceful grinding during ongoing SB events may have caused canine attrition in this patient. PMID- 27354031 TI - Functional strength training: Seated machine vs standing cable training to improve physical function in elderly. AB - BACKGROUND: The majority of the strength training studies in older adults have incorporated fixed-form exercises using seated resistance training machines. In light of the modest improvements in physical function shown in these studies, functional or task-specific exercises, involving movement patterns that mimic daily activities, have been studied. Free-form exercises, using free-weights or cable, is another form of functional strength training. Currently, no intervention studies exist comparing free-form exercises, using cable machines, and fixed-form exercises, using seated machines in older adults. METHODS: A total of 29 independently-living older adults, 65years or older, were randomized into two groups, seated machine (SM, n=10) and standing cable (SC, n=12). After 12weeks of training twice per week, groups were compared. The primary outcome was the Physical Performance Battery (PPB), a measure of physical function. Secondary outcomes were lower and upper body strength and power, activities of daily living evaluated by multiple tests including: Physical Performance Test (PPT), pan carry and gallon jug transfers, ratings of perceived exertion (RPE), and self-reported function using Patient Reported Outcomes Measurement Information System (PROMIS). Outcome assessors were blinded to participants' intervention assignments. RESULTS: The PPB (SC=0.23 points; SM=0.15 points) showed clinical and significant improvements, but there was no significant difference between the groups (g=0.2, 95% CI (-0.6, 1.0). For secondary outcomes, chair stand (g=0.7, 95% CI (0.2, 1.6), p=0.03) and pan carry (g=0.8, 95% CI (0.07, 1.07), p=0.04) favored SC, while chest press 1RM (g=0.2, 95% CI (0.06, 1.1), p=0.02) favored SM. There were no statistically significant group differences between PPB, gallon jug transfer, leg press 1RM, power, RPE or self-reported function. CONCLUSIONS: Standing cable training was not superior to seated machine training in improving physical performance in older adults. However, both training interventions were effective in improving function. The findings also suggest that exercise specificity should be considered when prescribing resistance exercises to improve physical function in older adults. PMID- 27354032 TI - Delivery of minimally dispersed liquid interfaces for sequential surface chemistry. AB - We present a method for sequential delivery of reagents to a reaction site with minimal dispersion of their interfaces. Using segmented flow to encapsulate the reagents as droplets, the dispersion between reagent plugs remains confined in a limited volume, while being transmitted to the reaction surface. In close proximity to the target surface, we use a passive array of microstructures for removal of the oil phase such that the original reagent sequence is reconstructed, and only the aqueous phase reaches the reaction surface. We provide a detailed analysis of the conditions under which the method can be applied and demonstrate maintaining a transition time of 560 ms between reagents transported to a reaction site over a distance of 60 cm. We implemented the method using a vertical microfluidic probe on an open surface, allowing contact free interaction with biological samples, and demonstrated two examples of assays implemented using the method: measurements of receptor-ligand reaction kinetics and of the fluorescence response of immobilized GFP to local variations in pH. We believe that the method can be useful for studying the dynamic response of cells and proteins to various stimuli, as well as for highly automated multi-step assays. PMID- 27354033 TI - Citizens' juries could help to guide screening policy. PMID- 27354034 TI - Clinical Manifestations of Laryngopharyngeal Reflux. PMID- 27354035 TI - The Gastric and Duodenal Eosinophilia in Functional Dyspepsia. PMID- 27354036 TI - Probiotic Yeast Therapy for Irritable Bowel Syndrome. PMID- 27354037 TI - Obtaining i.v. fosfomycin through an expanded-access protocol. AB - PURPOSE: One hospital's experience with procuring i.v. fosfomycin via an expanded access protocol to treat a panresistant infection is described. SUMMARY: In mid 2014, a patient at a tertiary care institution had an infection caused by a gram negative pathogen expressing notable drug resistance. Once it was determined by the infectious diseases (ID) attending physician that i.v. fosfomycin was a possible treatment for this patient, the ID pharmacist began the process of drug procurement. The research and ID pharmacists completed an investigational new drug (IND) application, which required patient-specific details and contributions from the ID physician. After obtaining approval of the IND, an Internet search identified a product vendor in the United Kingdom, who was then contacted to begin the drug purchasing and acquisition processes. Authorization of the transaction required signatures from key senior hospital administrators, including the chief financial officer and the chief operating officer. Approximately 6 days after beginning the acquisition process, the research pharmacist arranged for the wholesaler to expedite product delivery. The ID pharmacist contacted the wholesaler's shipping company at the U.S. Customs Office, providing relevant contact information to ensure that any unexpected circumstances could be quickly addressed. The product arrived at the U.S. Customs Office 8 days after beginning the acquisition process and was held in the U.S. Customs Office for 2 days. The patient received the first dose of i.v. fosfomycin 13 days after starting the expanded-access protocol process. CONCLUSION: I.V. fosfomycin was successfully procured through an FDA expanded-access protocol by coordinating efforts among ID physicians, pharmacists, and hospital executives. PMID- 27354038 TI - Long-term pharmacotherapy considerations in the bariatric surgery patient. AB - PURPOSE: Pharmacists' role in optimizing long-term pharmacotherapy for bariatric surgery patients is detailed. SUMMARY: Bariatric surgery patients provide a difficult challenge in terms of many pharmacotherapy issues, especially in the chronic care setting, where data on long-term effects of bariatric surgery are limited. The most common procedures are Roux-en-Y gastric bypass (RYGB), adjustable gastric banding, and sleeve gastrectomy. Sleeve gastrectomy has become the most common procedure in the United States, primarily because it has less overall chronic malabsorption effects than RYGB. Pharmacotherapy management is complicated by rapid weight loss combined with a number of pharmacokinetic changes, such as decreased absorption of some medications due to altered gastrointestinal tract anatomy and potentially increased concentrations of some medications due to a decreased volume of distribution resulting from weight loss. Nutritional and metabolic supplementation are of the utmost importance in order to limit deficiencies that can lead to a number of conditions. Many chronic diseases, including hypertension, diabetes, gastroesophageal reflux disease, and urinary incontinence, are improved by bariatric surgery but require close monitoring to ensure the effectiveness of maintenance pharmacotherapy and avoidance of adverse effects. Psychotropic medication management is also an important pharmacotherapy concern, as evidenced by antidepressants being the most commonly used medication class among preoperative bariatric surgery patients. CONCLUSION: Pharmacists have an increasing role in the chronic management of the bariatric surgery patient due to their knowledge of medication dosage forms and expertise in disease states affected by bariatric surgery. PMID- 27354039 TI - Assessment of inpatient admissions and top 25 medications for obese pediatric patients at two academic hospitals. AB - PURPOSE: Inpatient admissions and the top 25 medications for obese pediatric patients at two academic hospitals were assessed. METHODS: Children age 2-17 years were included if they were obese and admitted to either hospital on or after January 1, 2011, and discharged before December 31, 2011. Obesity was defined as a body mass index of >=95th percentile for age and sex. The objectives of this study were to determine the percentage of hospital admissions involving obese children and compile a list of medications prescribed to these patients. The top 25 medications prescribed were further evaluated to determine their pharmacokinetic disposition in obese patients. RESULTS: Obese children accounted for 18.8% of the 15,119 admissions for children age 2-17 years at the two study hospitals. No significant difference was noted in the number of obese pediatric children admitted between institutions. A total of 28,234 medications were ordered for this population, with a median number of 8 medications prescribed per admission. Sixteen of the same medications (64.0%) ranked in the top 25 at each facility. The most commonly prescribed medications for these patients included analgesics, antimicrobials, corticosteroids, bronchodilators, and gastrointestinal agents. CONCLUSION: Obese children accounted for 18.8% of admissions for patients age 2-17 years at two academic hospitals over a 1-year period. The most commonly prescribed medications for these children included analgesics, antimicrobials, corticosteroids, bronchodilators, and gastrointestinal agents. The literature guiding the dosing of these medications in this population was limited to seven studies, representing just three medications. PMID- 27354040 TI - Olodaterol for the treatment of chronic obstructive pulmonary disease. AB - PURPOSE: Published data on the pharmacology, pharmacokinetics, efficacy, and safety of the once-daily, long-acting beta2-agonist (LABA) olodaterol are reviewed. SUMMARY: Olodaterol (Striverdi Respimat, Boehringer Ingelheim), a LABA with high selectivity for beta2-adrenergic receptors, is indicated for the treatment of chronic obstructive pulmonary disease (COPD); the recommended dose is 5 MUg, to be delivered once daily via the Respimat inhaler. In 48- and 6-week Phase III clinical trials of olodaterol evaluating various lung function and symptomatic outcomes in patients with moderate to very severe COPD, olodaterol use was associated with significant improvements in spirometry outcomes, such as postbronchodilator forced expiratory volume in one second (FEV1), as well as dyspnea severity and quality-of-life measures. Other clinical trials demonstrated that olodaterol produced beneficial effects on FEV1 measures throughout the 24 hour dosing interval. A meta-analysis of data from 20 published research reports indicated that olodaterol's efficacy was comparable to that of the once-daily LABA indacaterol and that the combination of olodaterol and tiotropium provided improvements in lung function greater than those provided by tiotropium alone. Analysis of pooled data from four long-term trials showed that olodaterol's safety profile was comparable to that of formoterol; the most frequently reported adverse effects associated with olodaterol use were bronchitis, nasopharyngitis, and upper respiratory tract infection. CONCLUSION: Once-daily olodaterol 5 MUg is an effective therapy in improving lung function and symptomatic outcomes in patients with moderate to very severe COPD receiving other maintenance therapy, with a satisfactory safety profile. PMID- 27354042 TI - Resolution of abnormal cardiac MRI T2 signal following immune suppression for cardiac sarcoidosis. AB - Cardiac MR (CMR) with late gadolinium enhancement is commonly used to detect cardiac damage in the setting of cardiac sarcoidosis. The addition of T2 mapping to CMR was recently shown to enhance cardiac sarcoidosis detection and correlates with increased cardiac arrhythmia risk. This study was conducted to determine if CMR T2 abnormalities and related arrhythmias are reversible following immune suppression therapy. A retrospective study of subjects with cardiac sarcoidosis with abnormal T2 signal on baseline CMR and a follow-up CMR study at least 4 months later was conducted at The Ohio State University from 2011 to 2015. Immune suppression treated participants had a significant reduction in peak myocardial T2 value (70.0+/-5.5 vs 59.2+/-6.1 ms, pretreatment vs post-treatment; p=0.017), and 83% of immune suppression treated subjects had objective improvement in cardiac arrhythmias. Two subjects who had received inadequate immune suppression treatment experienced progression of cardiac sarcoidosis. This report indicates that abnormal CMR T2 signal represents an acute inflammatory manifestation of cardiac sarcoidosis that is potentially reversible with adequate immune suppression therapy. PMID- 27354041 TI - Aurora A, MCAK, and Kif18b promote Eg5-independent spindle formation. AB - Inhibition of the microtubule (MT) motor protein Eg5 results in a mitotic arrest due to the formation of monopolar spindles, making Eg5 an attractive target for anti-cancer therapies. However, Eg5-independent pathways for bipolar spindle formation exist, which might promote resistance to treatment with Eg5 inhibitors. To identify essential components for Eg5-independent bipolar spindle formation, we performed a genome-wide siRNA screen in Eg5-independent cells (EICs). We find that the kinase Aurora A and two kinesins, MCAK and Kif18b, are essential for bipolar spindle assembly in EICs and in cells with reduced Eg5 activity. Aurora A promotes bipolar spindle assembly by phosphorylating Kif15, hereby promoting Kif15 localization to the spindle. In turn, MCAK and Kif18b promote bipolar spindle assembly by destabilizing the astral MTs. One attractive way to interpret our data is that, in the absence of MCAK and Kif18b, excessive astral MTs generate inward pushing forces on centrosomes at the cortex that inhibit centrosome separation. Together, these data suggest a novel function for astral MTs in force generation on spindle poles and how proteins involved in regulating microtubule length can contribute to bipolar spindle assembly. PMID- 27354043 TI - Beneficial effects of long-acting nifedipine on coronary vasomotion abnormalities after drug-eluting stent implantation: The NOVEL study. AB - AIMS: It is widely known that drug-eluting stents (DES) induce coronary vasomotion abnormalities. We have previously demonstrated that chronic treatment with long-acting nifedipine suppresses coronary hyperconstricting responses induced by the first-generation DES (e.g. sirolimus- and pacritaxel-eluting stents) through inhibition of vascular inflammation in pigs. To examine whether this is also the case with the second-generation DES (everolimus-eluting stents, EES) in humans, the most widely used DES in the world, we conducted a prospective, randomized, multicentre trial, termed as the NOVEL Study. METHODS AND RESULTS: We evaluated 100 patients with stable angina pectoris who underwent scheduled implantation of EES in the left coronary arteries. They were randomly assigned to receive either conventional treatments alone or additionally long acting nifedipine (10-60 mg/day) (n = 50 each). After 8-10 months, 37 patients in the control and 38 in the nifedipine group were examined for coronary vasoreactivity to intracoronary acetylcholine (ACh) by quantitative coronary angiography after 48-h withdrawal of nifedipine. Coronary vasoconstricting responses to ACh were significantly enhanced at the distal edge of EES compared with non-stented vessel (P = 0.0001) and were significantly suppressed in the nifedipine group compared with the control group (P = 0.0044). Furthermore, the inflammatory profiles were also improved only in the nifedipine group, which evaluated by serum levels of high-sensitivity CRP (P = 0.0001) and adiponectin (P = 0.0039). CONCLUSIONS: These results indicate that DES-induced coronary vasomotion abnormalities still remain an important clinical issue even with the second-generation DES, for which long-acting nifedipine exerts beneficial effects associated with its anti-inflammatory effects. TRIAL REGISTRATION: This study is registered at the UMIN Clinical Trial Registry (UMIN-CTR; ID=UMIN000015147). PMID- 27354045 TI - Typical STEMI: or not? Embolic left anterior descending artery occlusion, fulminant pulmonary embolism, and in-transit thrombus in a patent foramen ovale. PMID- 27354044 TI - Geographic variations in the PARADIGM-HF heart failure trial. AB - AIMS: The globalization of clinical trials has highlighted geographic variations in patient characteristics, event rates, and treatment effects. We investigated these further in PARADIGM-HF, the largest and most globally representative trial in heart failure (HF) to date. METHODS AND RESULTS: We looked at five regions: North America (NA) 602 (8%), Western Europe (WE) 1680 (20%), Central/Eastern Europe/Russia (CEER) 2762 (33%), Latin America (LA) 1433 (17%), and Asia-Pacific (AP) 1487 (18%). Notable differences included: WE patients (mean age 68 years) and NA (65 years) were older than AP (58 years) and LA (63 years) and had more coronary disease; NA and CEER patients had the worst signs, symptoms, and functional status. North American patients were the most likely to have a defibrillating-device (54 vs. 2% AP) and least likely prescribed a mineralocorticoid receptor antagonist (36 vs. 65% LA). Other evidence-based therapies were used most frequently in NA and WE. Rates of the primary composite outcome of cardiovascular (CV) death or HF hospitalization (per 100 patient years) varied among regions: NA 13.6 (95% CI 11.7-15.7) WE 9.6 (8.6-10.6), CEER 12.3 (11.4-13.2), LA 11.2 (10.0-12.5), and AP 12.5 (11.3-13.8). After adjustment for prognostic variables, relative to NA, the risk of CV death was higher in LA and AP and the risk of HF hospitalization lower in WE. The benefit of sacubitril/valsartan was consistent across regions. CONCLUSION: There were many regional differences in PARADIGM-HF, including in age, symptoms, comorbidity, background therapy, and event-rates, although these did not modify the benefit of sacubitril/valsartan. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255. PMID- 27354047 TI - Abnormal right ventricular-pulmonary artery coupling with exercise in heart failure with preserved ejection fraction. AB - BACKGROUND: Exercise intolerance is common in people with heart failure and preserved ejection fraction (HFpEF). Right ventricular (RV) dysfunction has been shown at rest in HFpEF but little data are available regarding dynamic RV pulmonary artery (PA) coupling during exercise. METHODS AND RESULTS: Subjects with HFpEF (n = 50) and controls (n = 24) prospectively underwent invasive cardiopulmonary exercise testing using high-fidelity micromanometer catheters along with simultaneous assessment of RV and left ventricular (LV) mechanics by echocardiography. Compared with controls at rest, subjects with HFpEF displayed preserved RV systolic and diastolic mechanics (RV s' and e'), impaired LV s' and e', higher biventricular filling pressures, and higher pulmonary artery pressures. On exercise, subjects with HFpEF displayed less increase in stroke volume, heart rate, and cardiac output (CO), with blunted increase in CO relative to O2 consumption (VO2). Enhancement in RV systolic and diastolic function on exercise was impaired in HFpEF compared with controls. Exercise-induced PA vasodilation was reduced in HFpEF in correlation with greater venous hypoxia. Elevations in biventricular filling pressures and limitations in CO reserve were strongly correlated with abnormal enhancement in ventricular mechanics in the RV and LV during stress. CONCLUSIONS: In addition to limited LV reserve, patients with HFpEF display impaired RV reserve during exercise that is associated with high filling pressures and inadequate CO responses. These findings highlight the importance of biventricular dysfunction in HFpEF and suggest that novel therapies targeting myocardial reserve in both the left and right heart may be effective to improve clinical status. PMID- 27354046 TI - Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study. AB - Aims: Intravenous procainamide and amiodarone are drugs of choice for well tolerated ventricular tachycardia. However, the choice between them, even according to Guidelines, is unclear. We performed a multicentre randomized open labelled study to determine the safety and efficacy of intravenous procainamide and amiodarone for the acute treatment of tolerated wide QRS complex (probably ventricular) tachycardia. Methods and results: Patients were randomly assigned to receive intravenous procainamide (10 mg/kg/20 min) or amiodarone (5 mg/kg/20 min). The primary endpoint was the incidence of major predefined cardiac adverse events within 40 min after infusion initiation. Of 74 patients included, 62 could be analysed. The primary endpoint occurred in 3 of 33 (9%) procainamide and 12 of 29 (41%) amiodarone patients (odd ratio, OR = 0.1; 95% confidence interval, CI 0.03-0.6; P = 0.006). Tachycardia terminated within 40 min in 22 (67%) procainamide and 11 (38%) amiodarone patients (OR = 3.3; 95% CI 1.2-9.3; P = 0.026). In the following 24 h, adverse events occurred in 18% procainamide and 31% amiodarone patients (OR: 0.49; 95% CI: 0.15-1.61; P: 0.24). Among 49 patients with structural heart disease, the primary endpoint was less common in procainamide patients (3 [11%] vs. 10 [43%]; OR: 0.17; 95% CI: 0.04-0.73, P = 0.017). Conclusions: This study compares for the first time in a randomized design intravenous procainamide and amiodarone for the treatment of the acute episode of sustained monomorphic well-tolerated (probably) ventricular tachycardia. Procainamide therapy was associated with less major cardiac adverse events and a higher proportion of tachycardia termination within 40 min. PMID- 27354048 TI - Acute stent thrombosis unveils two electrocardiogram patterns in a patient with 'De Winter T-waves' anterior myocardial infarction. PMID- 27354050 TI - The BIOSOLVE II trial: a step forward for the bioresorbable scaffold? PMID- 27354049 TI - Large-scale community echocardiographic screening reveals a major burden of undiagnosed valvular heart disease in older people: the OxVALVE Population Cohort Study. AB - BACKGROUND: Valvular heart disease (VHD) is expected to become more common as the population ages. However, current estimates of its natural history and prevalence are based on historical studies with potential sources of bias. We conducted a cross-sectional analysis of the clinical and epidemiological characteristics of VHD identified at recruitment of a large cohort of older people. METHODS AND RESULTS: We enrolled 2500 individuals aged >=65 years from a primary care population and screened for undiagnosed VHD using transthoracic echocardiography. Newly identified (predominantly mild) VHD was detected in 51% of participants. The most common abnormalities were aortic sclerosis (34%), mitral regurgitation (22%), and aortic regurgitation (15%). Aortic stenosis was present in 1.3%. The likelihood of undiagnosed VHD was two-fold higher in the two most deprived socioeconomic quintiles than in the most affluent quintile, and three-fold higher in individuals with atrial fibrillation. Clinically significant (moderate or severe) undiagnosed VHD was identified in 6.4%. In addition, 4.9% of the cohort had pre-existing VHD (a total prevalence of 11.3%). Projecting these findings using population data, we estimate that the prevalence of clinically significant VHD will double before 2050. CONCLUSIONS: Previously undetected VHD affects 1 in 2 of the elderly population and is more common in lower socioeconomic classes. These unique data demonstrate the contemporary clinical and epidemiological characteristics of VHD in a large population-based cohort of older people and confirm the scale of the emerging epidemic of VHD, with widespread implications for clinicians and healthcare resources. PMID- 27354051 TI - Serial 18F-fluorodeoxyglucose positron emission tomography/CT angiography in transcatheter-implanted aortic valve endocarditis. PMID- 27354052 TI - The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge. AB - The incidence of ST segment elevation myocardial infarction (STEMI) has decreased over the last two decades in developed countries, but mortality from STEMI despite widespread access to reperfusion therapy is still substantial as is the development of heart failure, particularly among an expanding older population. In developing countries, the incidence of STEMI is increasing and interventional reperfusion is often not available. We here review the pathophysiology of acute myocardial infarction and reperfusion, notably the temporal and spatial evolution of ischaemic and reperfusion injury, the different modes of cell death, and the resulting coronary microvascular dysfunction. We then go on to briefly characterize the cardioprotective phenomena of ischaemic preconditioning, ischaemic postconditioning, and remote ischaemic conditioning and their underlying signal transduction pathways. We discuss in detail the attempts to translate conditioning strategies and drug therapy into the clinical setting. Most attempts have failed so far to reduce infarct size and improve clinical outcomes in STEMI patients, and we discuss potential reasons for such failure. Currently, it appears that remote ischaemic conditioning and a few drugs (atrial natriuretic peptide, exenatide, metoprolol, and esmolol) reduce infarct size, but studies with clinical outcome as primary endpoint are still underway. PMID- 27354053 TI - The dream of near-zero X-rays ablation comes true. AB - While radiation exposure related to natural sources plays a minor role, medicine related exposure, represents, to date, a major exposure source. Within this exposure interventional electrophysiology is a relevant contributor. Unfortunately, no safe dose in radioprotection exists, the negative acute and long-term effects of radiological exposure may emerge at any radiation exposure dose. For this reason, patients and physicians should be aware of the risk of radiation exposure and the benefits of the imaging/procedure balanced by the required radiation exposure. Given this, performing a near to zero X-rays transcatheter ablation procedure should therefore represent an aim for all electrophysiological lab. Fortunately, the introduction of electroanatomic mapping systems, have provided the possibility to perform simple and complex electrophysiological procedures avoiding, or at least, limiting the use of radiations. The present review summarizes state of the art of feasibility and safety of the near to zero approach for the main electrophysiological procedures, highlighting the potential health benefits. PMID- 27354054 TI - Early experience of the trialign system for catheter-based treatment of severe tricuspid regurgitation. PMID- 27354055 TI - Let us preserve the harmonious development of transcatheter aortic valve implantation! PMID- 27354056 TI - A propitious time for initiating clinical trials in patients with heart failure with reduced ejection fraction and an estimated glomerular filtration rate <30 mL/min with an mineralocorticoid receptor antagonist and a K+ binder: 'the forbidden fruit'. PMID- 27354057 TI - Big data, smart computer systems, and doctor-patient relationship. PMID- 27354058 TI - Endo-epicardial dissociation in conduction. PMID- 27354059 TI - Acute thrombosis of left renal artery treated with thrombolysis and percutaneous transluminal angioplasty. PMID- 27354060 TI - Pressure-volume-loop-guided closure of an iatrogenic atrial septal defect for right heart failure following MitraClipTM-implantation. PMID- 27354061 TI - Oligomycins and pamamycin homologs impair motility and induce lysis of zoospores of the grapevine downy mildew pathogen, Plasmopara viticola. AB - Four antibiotics (pamamycin, oligomycin A, oligomycin B and echinosporin) were isolated and characterized from the fermentation broth of the marine Streptomyces strains B8496 and B8739. Bioassays revealed that each of these compounds impaired motility and caused subsequent lysis of P. viticola zoospores in a dose- and time dependent manner. Pamamycin displayed the strongest motility inhibitory and lytic activities (IC50 0.1 MUg mL(-1)) followed by oligomycin B (IC50 0.15 and 0.2 MUg mL(-1)) and oligomycin F (IC50 0.3 and 0.5 MUg mL(-1)). Oligomycin A and echinosporin also showed motility inhibitory activities against the zoospores with IC50 values of 3.0 and 10.0 MUg mL(-1), respectively. This is the first report of motility inhibitory and lytic activities of these antibiotics against zoospores of a phytopathogenic peronosporomycete. Structures of all the isolated compounds were determined based on detailed spectroscopic analysis. PMID- 27354062 TI - Coordinated Regulation of Cap-Dependent Translation and MicroRNA Function by Convergent Signaling Pathways. AB - Cell growth and proliferation require the coordinated activation of many cellular processes, including cap-dependent mRNA translation. MicroRNAs oppose cap dependent translation and set thresholds for expression of target proteins. Emerging data suggest that microRNA function is enhanced by cellular activation due in part to induction of the RNA-induced silencing complex (RISC) scaffold protein GW182. In the current study, we demonstrate that increased expression of GW182 in activated or transformed immune cells results from effects of phosphoinositol 3-kinase-Akt-mechanistic target of rapamycin (PI3K-Akt-mTOR) and Jak-Stat-Pim signaling on the translation of GW182 mRNA. Both signaling pathways enhanced polysome occupancy and eukaryotic initiation factor 4E (eIF4E) binding to the 5' 7mG cap of GW182 mRNA. The effect of Jak-Stat-Pim signaling on polysome occupancy and expression of GW182 protein was greater than that of PI3K-Akt-mTOR signaling, likely resulting from enhanced eIF4A-dependent unwinding of G quadruplexes in the 5' untranslated region of GW182 mRNA. Consistent with this, GW182 expression and microRNA function were reduced by inhibition of mTOR or Pim kinases, translation initiation complex assembly, or eIF4A function. Taken together, these data provide a mechanistic link between microRNA function and cap dependent translation that allows activated immune cells to maintain microRNA mediated repression of targets despite enhanced rates of protein synthesis. PMID- 27354063 TI - Cotranslational Intersection between the SRP and GET Targeting Pathways to the Endoplasmic Reticulum of Saccharomyces cerevisiae. AB - Targeting of transmembrane proteins to the endoplasmic reticulum (ER) proceeds via either the signal recognition particle (SRP) or the guided entry of tail anchored proteins (GET) pathway, consisting of Get1 to -5 and Sgt2. While SRP cotranslationally targets membrane proteins containing one or multiple transmembrane domains, the GET pathway posttranslationally targets proteins containing a single C-terminal transmembrane domain termed the tail anchor. Here, we dissect the roles of the SRP and GET pathways in the sorting of homologous, two-membrane-spanning K(+) channel proteins termed Kcv, Kesv, and Kesv-VV. We show that Kcv is targeted to the ER cotranslationally via its N-terminal transmembrane domain, while Kesv-VV is targeted posttranslationally via its C terminal transmembrane domain, which recruits Get4-5/Sgt2 and Get3. Unexpectedly, nascent Kcv recruited not only SRP but also the Get4-5 module of the GET pathway to ribosomes. Ribosome binding of Get4-5 was independent of Sgt2 and was strongly outcompeted by SRP. The combined data indicate a previously unrecognized cotranslational interplay between the SRP and GET pathways. PMID- 27354064 TI - Sterol Regulatory Element Binding Protein Regulates the Expression and Metabolic Functions of Wild-Type and Oncogenic IDH1. AB - Sterol regulatory element binding protein (SREBP) is a major transcriptional regulator of the enzymes underlying de novo lipid synthesis. However, little is known about the SREBP-mediated control of processes that indirectly support lipogenesis, for instance, by supplying reducing power in the form of NAPDH or directing carbon flux into lipid precursors. Here, we characterize isocitrate dehydrogenase 1 (IDH1) as a transcriptional target of SREBP across a spectrum of cancer cell lines and human cancers. IDH1 promotes the synthesis of lipids specifically from glutamine-derived carbons. Neomorphic mutations in IDH1 occur frequently in certain cancers, leading to the production of the oncometabolite 2 hydroxyglutarate (2-HG). We found that SREBP induces the expression of oncogenic IDH1 and influences 2-HG production from glucose. Treatment of cells with 25 hydroxycholesterol or statins, which respectively inhibit or activate SREBP, further supports SREBP-mediated regulation of IDH1 and, in cells with oncogenic IDH1, carbon flux into 2-HG. PMID- 27354065 TI - Phosphorylation of a Tyrosine Residue on Zap70 by Lck and Its Subsequent Binding via an SH2 Domain May Be a Key Gatekeeper of T Cell Receptor Signaling In Vivo. AB - The initiation of signaling in T lymphocytes in response to the binding of the T cell receptor (TCR) to cognate ligands is a key step in the emergence of adaptive immune responses. Conventional models posit that TCR signaling is initiated by the phosphorylation of receptor-associated immune receptor activation motifs (ITAMs). The cytoplasmic tyrosine kinase Zap70 binds to phosphorylated ITAMs, is subsequently activated, and then propagates downstream signaling. While evidence for such models is provided by experiments with cell lines, in vivo, Zap70 is bound to phosphorylated ITAMs in resting T cells. However, Zap70 is activated only upon TCR binding to cognate ligand. We report the results of computational studies of a new model for the initiation of TCR signaling that incorporates these in vivo observations. Importantly, the new model is shown to allow better and faster TCR discrimination between self-ligands and foreign ligands. The new model is consistent with many past experimental observations, and experiments that could further test the model are proposed. PMID- 27354066 TI - Heat Shock Factor 1 Is a Substrate for p38 Mitogen-Activated Protein Kinases. AB - Heat shock factor 1 (HSF1) monitors the structural integrity of the proteome. Phosphorylation at S326 is a hallmark for HSF1 activation, but the identity of the kinase(s) phosphorylating this site has remained elusive. We show here that the dietary agent phenethyl isothiocyanate (PEITC) inhibits heat shock protein 90 (Hsp90), the main negative regulator of HSF1; activates p38 mitogen-activated protein kinase (MAPK); and increases S326 phosphorylation, trimerization, and nuclear translocation of HSF1, and the transcription of a luciferase reporter, as well as the endogenous prototypic HSF1 target Hsp70. In vitro, all members of the p38 MAPK family rapidly and stoichiometrically catalyze the S326 phosphorylation. The use of stable knockdown cell lines and inhibitors indicated that among the p38 MAPKs, p38gamma is the principal isoform responsible for the phosphorylation of HSF1 at S326 in cells. A protease-mass spectrometry approach confirmed S326 phosphorylation and unexpectedly revealed that p38 MAPK also catalyzes the phosphorylation of HSF1 at S303/307, previously known repressive posttranslational modifications. Thus, we have identified p38 MAPKs as highly efficient catalysts for the phosphorylation of HSF1. Furthermore, our findings suggest that the magnitude and persistence of activation of p38 MAPK are important determinants of the extent and duration of the heat shock response. PMID- 27354067 TI - Follicle Depletion Provides a Permissive Environment for Ovarian Carcinogenesis. AB - We modeled the etiology of postmenopausal biology on ovarian cancer risk using germ cell-deficient white-spotting variant (Wv) mice, incorporating oncogenic mutations. Ovarian cancer incidence is highest in peri- and postmenopausal women, and epidemiological studies have established the impact of reproductive factors on ovarian cancer risk. Menopause as a result of ovarian follicle depletion is thought to contribute to higher cancer risk. As a consequence of follicle depletion, female Wv mice develop ovarian tubular adenomas, a benign epithelial tumor corresponding to surface epithelial invaginations and papillomatosis frequently found in postmenopausal human ovaries. Lineage tracing using MISR2-Cre indicated that the tubular adenomas that developed in Wv mice were largely derived from the MISR2 lineage, which marked only a fraction of ovarian surface and oviduct epithelial cells in wild-type tissues. Deletion of p27, either heterozygous or homozygous, was able to convert the benign tubular adenomas into more proliferative tumors. Restricted deletion of p53 in Wv/Wv mice by either intrabursal injection of adenoviral Cre or inclusion of the MISR2-Cre transgene also resulted in augmented tumor growth. This finding suggests that follicle depletion provides a permissive ovarian environment for oncogenic transformation of epithelial cells, presenting a mechanism for the increased ovarian cancer risk in postmenopausal women. PMID- 27354068 TI - Comparison of contemporary preoperative risk models at predicting acute kidney injury after isolated coronary artery bypass grafting: a retrospective cohort study. AB - OBJECTIVES: Acute kidney injury (AKI) after coronary artery bypass grafting (CABG) is associated with short-term and long-term adverse outcomes. The European System for Cardiac Operative Risk Evaluation (EuroSCORE), EuroSCORE II, the Society of Thoracic Surgeons (STS) score and Age, Creatinine and Ejection Fraction (ACEF) score, have been widely used for predicting the operative risk of cardiac surgery. The aim of this study is to investigate the discriminant ability among current available models in predicting postoperative AKI. METHODS: From January 2010 to December 2012, 353 patients who underwent isolated CABG were enrolled. The clinical characteristics, outcomes and scores of prognostic models were collected. The primary outcome was postoperative AKI, defined based on the Kidney Disease Improving Global Outcome (KDIGO) Clinical Practice Guideline for AKI, in 2012. RESULTS: 102 patients (28.9%) developed postoperative AKI. For AKI prediction, EuroSCORE II, STS score and ACEF score were all good tools for stage 3 AKI. The ACEF score was shown to have satisfied discriminant ability to predict postoperative AKI with area under a receiver operating characteristic curve: 0.781+/-0.027, (95% CI 0.729 to 0.834, p value <0.001). Multivariate logistic analysis identified that lower ejection fraction and higher serum creatinine were independent risk factors for AKI. CONCLUSIONS: The simple and extremely user friendly ACEF score can accurately identify the risk of postoperative AKI and has shown satisfactory discriminant ability when compared with other systems. The ACEF score might be the easiest tool for predicting postoperative AKI. PMID- 27354069 TI - What evidence is there for a delay in diagnostic coding of RA in UK general practice records? An observational study of free text. AB - OBJECTIVES: Much research with electronic health records (EHRs) uses coded or structured data only; important information captured in the free text remains unused. One dimension of EHR data quality assessment is 'currency' or timeliness, that is, data are representative of the patient state at the time of measurement. We explored the use of free text in UK general practice patient records to evaluate delays in recording of rheumatoid arthritis (RA) diagnosis. We also aimed to locate and quantify disease and diagnostic information recorded only in text. SETTING: UK general practice patient records from the Clinical Practice Research Datalink. PARTICIPANTS: 294 individuals with incident diagnosis of RA between 2005 and 2008; 204 women and 85 men, median age 63 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Assessment of (1) quantity and timing of text entries for disease-modifying antirheumatic drugs (DMARDs) as a proxy for the RA disease code, and (2) quantity, location and timing of free text information relating to RA onset and diagnosis. RESULTS: Inflammatory markers, pain and DMARDs were the most common categories of disease information in text prior to RA diagnostic code; 10-37% of patients had such information only in text. Read codes associated with RA-related text included correspondence, general consultation and arthritis codes. 64 patients (22%) had DMARD text entries >14 days prior to RA code; these patients had more and earlier referrals to rheumatology, tests, swelling, pain and DMARD prescriptions, suggestive of an earlier implicit diagnosis than was recorded by the diagnostic code. CONCLUSIONS: RA-related symptoms, tests, referrals and prescriptions were recorded in free text with 22% of patients showing strong evidence of delay in coding of diagnosis. Researchers using EHRs may need to mitigate for delayed codes by incorporating text into their case ascertainment strategies. Natural language processing techniques have the capability to do this at scale. PMID- 27354070 TI - A school-based intervention incorporating smartphone technology to improve health related fitness among adolescents: rationale and study protocol for the NEAT and ATLAS 2.0 cluster randomised controlled trial and dissemination study. AB - INTRODUCTION: Physical inactivity has been described as a global pandemic. Interventions aimed at developing skills in lifelong physical activities may provide the foundation for an active lifestyle into adulthood. In general, school based physical activity interventions targeting adolescents have produced modest results and few have been designed to be 'scaled-up' and disseminated. This study aims to: (1) assess the effectiveness of two physical activity promotion programmes (ie, NEAT and ATLAS) that have been modified for scalability; and (2) evaluate the dissemination of these programmes throughout government funded secondary schools. METHODS AND ANALYSIS: The study will be conducted in two phases. In the first phase (cluster randomised controlled trial), 16 schools will be randomly allocated to the intervention or a usual care control condition. In the second phase, the Reach, Effectiveness, Adoption, Implementation and Maintenance (Re-AIM) framework will be used to guide the design and evaluation of programme dissemination throughout New South Wales (NSW), Australia. In both phases, teachers will be trained to deliver the NEAT and ATLAS programmes, which will include: (1) interactive student seminars; (2) structured physical activity programmes; (3) lunch-time fitness sessions; and (4) web-based smartphone apps. In the cluster RCT, study outcomes will be assessed at baseline, 6 months (primary end point) and 12-months. Muscular fitness will be the primary outcome and secondary outcomes will include: objectively measured body composition, cardiorespiratory fitness, flexibility, resistance training skill competency, physical activity, self-reported recreational screen-time, sleep, sugar-sweetened beverage and junk food snack consumption, self-esteem and well-being. ETHICS AND DISSEMINATION: This study has received approval from the University of Newcastle (H-2014-0312) and the NSW Department of Education (SERAP: 2012121) human research ethics committees. This study is funded by the Australian Research Council (FT140100399) and the NSW Department of Education. TRIAL REGISTRATION NUMBER: ACTRN12615000360516; Pre-results. PMID- 27354071 TI - Preferences for ARV-based HIV prevention methods among men and women, adolescent girls and female sex workers in Gauteng Province, South Africa: a protocol for a discrete choice experiment. AB - INTRODUCTION: For the past few decades, condoms have been the main method of HIV prevention. Recent advances in antiretroviral (ARV)-based prevention products have substantially changed the prevention landscape, yet little is known about how popular these products will be among potential users, or whether new methods might be used in conjunction with, or instead of, condoms. This study will use a discrete choice experiment (DCE) to (1) explore potential users' preferences regarding HIV prevention products, (2) quantify the importance of product attributes and (3) predict the uptake of products to inform estimates of their potential impact on the HIV epidemic in South Africa. We consider preferences for oral pre-exposure prophylaxis; a vaginal microbicide gel; a long-acting vaginal ring; a SILCS diaphragm used in concert with gel; and a long-acting ARV-based injectable. METHODS AND ANALYSIS: This study will gather data from 4 populations: 200 women, 200 men, 200 adolescent girls (aged 16-17 years) and 200 female sex workers. The DCE attributes and design will be developed through a literature review, supplemented by a thematic analysis of qualitative focus group discussions. Extensive piloting will be carried out in each population through semistructured interviews. The final survey will be conducted using computer tablets via a household sample (for women, men and adolescents) and respondent driven sampling (for female sex workers), and DCE data analysed using a range of multinomial logit models. ETHICS AND DISSEMINATION: This study has been approved by the University of the Witwatersrand Human Research Ethics Committee and the Research Ethics Committee at the London School of Hygiene and Tropical Medicine. Findings will be presented to international conferences and peer-reviewed journals. Meetings will be held with opinion leaders in South Africa, while results will be disseminated to participants in Ekurhuleni through a public meeting or newsletter. PMID- 27354073 TI - Association of physical activity with cognition, metacognition and academic performance in children and adolescents: a protocol for systematic review and meta-analysis. AB - INTRODUCTION: Schools provide a relevant context for improving children's and adolescents' physical and mental health by increasing physical activity during school hours and/or beyond. The interest in the relationship between physical activity programmes and cognition during development has recently increased, with evidence suggesting a positive association. We present a protocol of systematic reviews and meta-analysis of intervention studies that, by determining the effects of chronic physical exercise on children's and adolescents' cognitive and metacognitive functions, cognitive life skills, academic behaviours and achievement, aims to ensure procedural objectivity and transparency, and maximise the extraction of relevant information to inform policy development. METHODS: This protocol is guided by Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) and by the Cochrane Collaboration Handbook. Databases to be utilised for a thorough selection of the pertinent literature are MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science, PsycINFO and ERIC. Selection is proposed to encompass an international and a national publication level, with inclusion of experimental studies written in English or in Spanish, respectively. Also, relevant references included in the selected studies will be considered suitable for review as supplemental sources.We present an integrated approach to the methodological quality assessment of the selected studies, including the Jadad Scale for the assessment of the quality of randomised controlled trials and the Quality Assessment Tool for Quantitative Studies for pre-post studies and non randomised controlled trials. The pre-post interventions mean differences will be the primary indicator of the intervention outcome. STATISTICAL ANALYSIS: A subgroup analysis is proposed based on cognitive functions and their neural correlates, metacognitive functions and cognitive life skills, academic achievement areas and academic behaviours. TRIAL REGISTRATION NUMBER: PROSPERO CRD42015029913. PMID- 27354072 TI - Utility of models to predict 28-day or 30-day unplanned hospital readmissions: an updated systematic review. AB - OBJECTIVE: To update previous systematic review of predictive models for 28-day or 30-day unplanned hospital readmissions. DESIGN: Systematic review. SETTING/DATA SOURCE: CINAHL, Embase, MEDLINE from 2011 to 2015. PARTICIPANTS: All studies of 28-day and 30-day readmission predictive model. OUTCOME MEASURES: Characteristics of the included studies, performance of the identified predictive models and key predictive variables included in the models. RESULTS: Of 7310 records, a total of 60 studies with 73 unique predictive models met the inclusion criteria. The utilisation outcome of the models included all-cause readmissions, cardiovascular disease including pneumonia, medical conditions, surgical conditions and mental health condition-related readmissions. Overall, a wide range C-statistic was reported in 56/60 studies (0.21-0.88). 11 of 13 predictive models for medical condition-related readmissions were found to have consistent moderate discrimination ability (C-statistic >=0.7). Only two models were designed for the potentially preventable/avoidable readmissions and had C statistic >0.8. The variables 'comorbidities', 'length of stay' and 'previous admissions' were frequently cited across 73 models. The variables 'laboratory tests' and 'medication' had more weight in the models for cardiovascular disease and medical condition-related readmissions. CONCLUSIONS: The predictive models which focused on general medical condition-related unplanned hospital readmissions reported moderate discriminative ability. Two models for potentially preventable/avoidable readmissions showed high discriminative ability. This updated systematic review, however, found inconsistent performance across the included unique 73 risk predictive models. It is critical to define clearly the utilisation outcomes and the type of accessible data source before the selection of the predictive model. Rigorous validation of the predictive models with moderate-to-high discriminative ability is essential, especially for the two models for the potentially preventable/avoidable readmissions. Given the limited available evidence, the development of a predictive model specifically for paediatric 28-day all-cause, unplanned hospital readmissions is a high priority. PMID- 27354074 TI - Evaluating the accessibility and utility of HIV-related point-of-care diagnostics for maternal health in rural South Africa: a study protocol. AB - INTRODUCTION: Poor healthcare access is a major barrier to receiving antenatal care and a cause of high maternal mortality in South Africa (SA). 'Point-of-care' (POC) diagnostics is a powerful emerging healthcare approach to improve healthcare access. This study focuses on evaluating the accessibility and utility of POC diagnostics for maternal health in rural SA primary healthcare (PHC) clinics in order to generate a model framework of implementation of POC diagnostics in rural South African clinics. METHOD AND ANALYSES: We will use several research methods, including a systematic review, quasi-experiments, survey, key informant interviews and audits. We will conduct a systematic review and experimental study to determine the impact of POC diagnostics on maternal health. We will perform a cross-sectional case study of 100 randomly selected rural primary healthcare clinics in KwaZulu-Natal to measure the context and patterns of POC diagnostics access and usage by maternal health providers and patients. We will conduct interviews with relevant key stakeholders to determine the reasons for POC deficiencies regarding accessibility and utility of HIV related POC diagnostics for maternal health. We will also conduct a vertical audit to investigate all the quality aspects of POC diagnostic services including diagnostic accuracy in a select number of clinics. On the basis of information gathered, we will propose a model framework for improved implementation of POC diagnostics in rural South African public healthcare clinics. Statistical (Stata 13) and thematic (NVIVO) data analysis will be used in this study. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the University of KwaZulu-Natal (BE 484/14) and the KwaZulu-Natal Department of Health based on the Helsinki Declaration (HRKM 40/15). Findings of this study will be disseminated electronically and in print. They will be presented to conferences related to HIV/AIDS, diagnostics, maternal health and strengthening of health systems. PMID- 27354075 TI - Association between markers of glucose metabolism and risk of colorectal cancer. AB - OBJECTIVES: Independent epidemiological studies have evaluated the association between markers of glucose metabolism (including fasting glucose, fasting insulin, homeostasis model of risk assessment-insulin resistance (HOMA-IR), glycated haemoglobin (HbA1c) and C peptide) and the risk of colorectal cancer (CRC). However, such associations have not been systematically analysed and no clear conclusions have been drawn. Therefore, we addressed this issue using a meta-analysis approach. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed and EMBASE were searched up to May 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: Either a fixed-effects or random-effects model was adopted to estimate overall ORs for the association between markers of glucose metabolism and the risk of CRC. In addition, dose-response, meta-regression, subgroup and publication bias analyses were conducted. RESULTS: 35 studies involving 25 566 patients and 5 706 361 participants were included. Higher levels of fasting glucose, fasting insulin, HOMA-IR, HbA1c and C peptide were all significantly associated with increased risk of CRC (fasting glucose, pooled OR=1.12, 95% CI 1.06 to 1.18; fasting insulin, pooled OR=1.42, 95% CI 1.19 to 1.69; HOMA-IR, pooled OR=1.47, 95% CI 1.24 to 1.74; HbA1c, pooled OR=1.22, 95% CI 1.02 to 1.47 (with borderline significance); C peptide, pooled OR=1.27, 95% CI 1.08 to 1.49). Subgroup analysis suggested that a higher HOMA-IR value was significantly associated with CRC risk in all subgroups, including gender, study design and geographic region. For the relative long-term markers, the association was significant for HbA1c in case-control studies, while C peptide was significantly associated with CRC risk in both the male group and colon cancer. CONCLUSIONS: The real-time composite index HOMA-IR is a better indicator for CRC risk than are fasting glucose and fasting insulin. The relative long-term markers, HbA1c and C peptide, are also valid predictors for CRC risk. Considering the included case control studies in the current analysis, more cohort studies are warranted to enhance future analysis. PMID- 27354076 TI - Prevalence of clinically significant decisional conflict: an analysis of five studies on decision-making in primary care. AB - OBJECTIVES: Unresolved clinically significant decisional conflict (CSDC) in patients following a consultation with health professionals is often the result of inadequate patient involvement in decision-making and may result in poor outcomes. We sought to identify the prevalence of CSDC in studies on decision making in primary care and to explore its risk factors. SETTING: We performed a secondary analysis of existing data sets from studies conducted in Primary Care Practice-Based Research Networks in Quebec and Ontario, Canada. PARTICIPANTS: Eligible studies included a patient-reported measure on the 16-item Decisional Conflict Scale (DCS) following a decision made with a healthcare professional with no study design restriction. PRIMARY AND SECONDARY OUTCOME MEASURES: CSDC was defined as a score >=25/100 on the DCS. The prevalence of CSDC was stratified by sex; and patient-level logistic regression analysis was performed to explore its potential risk factors. Data sets of studies were analysed individually and qualitatively compared. RESULTS: 5 projects conducted between 2003 and 2010 were included. They covered a range of decisions: prenatal genetic screening, antibiotics for acute respiratory infections and miscellaneous. Altogether, the 5 projects gathered data from encounters with a total of 1338 primary care patients (69% female; range of age 15-83). The prevalence of CSDC in patients varied across studies and ranged from 10.3% (95% CI 7.2% to 13.4%) to 31.1% (95% CI 26.6% to 35.6%). Across the 5 studies, risk factors of CSDC included being male, living alone and being 45 or older. CONCLUSIONS: Prevalence of CSDC in patients who had enrolled in studies conducted in primary care contexts was substantial and appeared to vary according to the type of decision as well as to patient characteristics such as sex, living arrangement and age. Patients presenting risk factors of CSDC should be offered tools to increase their involvement in decision making. PMID- 27354078 TI - Correction: Protocol for the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) study: a pragmatic, randomised clinical trial. PMID- 27354077 TI - Sources of social support associated with health and quality of life: a cross sectional study among Canadian and Latin American older adults. AB - OBJECTIVES: To examine whether the association between emotional support and indicators of health and quality of life differs between Canadian and Latin American older adults. DESIGN: Cross-sectional analysis of the International Mobility in Aging Study (IMIAS). Social support from friends, family members, children and partner was measured with a previously validated social network and support scale (IMIAS-SNSS). Low social support was defined as ranking in the lowest site-specific quartile. Prevalence ratios (PR) of good health, depression and good quality of life were estimated with Poisson regression models, adjusting for age, gender, education, income and disability in activities of daily living. SETTING: Kingston and Saint-Hyacinthe in Canada, Manizales in Colombia and Natal in Brazil. PARTICIPANTS: 1600 community-dwelling adults aged 65-74 years, n=400 at each site. OUTCOME MEASURES: Likert scale question on self-rated health, Center for Epidemiological Studies Depression Scale and 10-point analogical quality-of-life (QoL) scale. RESULTS: Relationships between social support and study outcomes differed between Canadian and Latin American older adults. Among Canadians, those without a partner had a lower prevalence of good health (PR=0.90; 95% CI 0.82 to 0.98), and those with high support from friends had a higher prevalence of good health (PR=1.09; 95% CI 1.01 to 1.18). Among Latin Americans, depression was lower among those with high levels of support from family (PR=0.63; 95% CI 0.48 to 0.83), children (PR=0.60; 95% CI 0.45 to 0.80) and partner (PR=0.57; 95% CI 0.31 to 0.77); good QoL was associated with high levels of support from children (PR=1.54; 95% CI 1.20 to 1.99) and partner (PR=1.31; 95% CI 1.03 to 1.67). CONCLUSIONS: Among older adults, different sources of support were relevant to health across societies. Support from friends and having a partner were related to good health in Canada, whereas in Latin America, support from family, children and partner were associated with less depression and better QoL. PMID- 27354079 TI - Protocol for a cluster randomised trial of a communication skills intervention for physicians to facilitate survivorship transition in patients with lymphoma. AB - INTRODUCTION: Survivors of cancer often describe a sense of abandonment post treatment, with heightened worry, uncertainty, fear of recurrence and limited understanding of what lies ahead. This study examines the efficacy of a communication skills training (CST) intervention to help physicians address survivorship issues and introduce a new consultation focused on the use of a survivorship care plan for patients with Hodgkin's lymphoma and diffuse large B cell lymphoma. METHODS AND ANALYSIS: Specifically, this randomised, 4-site trial will test the efficacy of a survivorship planning consultation (physicians receive CST and apply these skills in a new survivorship-focused office visit using a survivorship plan) with patients who have achieved complete remission after completion of first-line therapy versus a control arm in which physicians are trained to subsequently provide a time-controlled, manualised wellness rehabilitation consultation focused only on discussion of healthy nutrition and exercise as rehabilitation postchemotherapy. The primary outcome for physicians will be uptake and usage of communication skills and maintenance of these skills over time. The primary outcome for patients is changes in knowledge about lymphoma and adherence to physicians' recommendations (eg, pneumococcus and influenza vaccinations); secondary outcomes will include perceptions of the doctor-patient relationship, decreased levels of cancer worry and depression, quality of life changes, satisfaction with care and usage of healthcare. This study will also examine the moderators and mediators of change within our theoretical model derived from Leventhal's Common-Sense Model of health beliefs. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Boards at Memorial Sloan Kettering Cancer Centers and all other participating sites. This work is funded by the National Cancer Institute (R01 CA 151899 awarded to DWK and SH as coprincipal investigators). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute (NCI) or the National Institutes of Health (NIH). The study findings will be disseminated to the research and medical communities through publication in peer-reviewed journals and through presentations at local, national and international conferences. TRIAL REGISTRATION NUMBER: NCT01483664. PMID- 27354081 TI - Study protocol for the randomised controlled trial: combined multimarker screening and randomised patient treatment with ASpirin for evidence-based PREeclampsia prevention (ASPRE). AB - INTRODUCTION: Pre-eclampsia (PE) affects 2-3% of all pregnancies and is a major cause of maternal and perinatal morbidity and mortality. Prophylactic use of low dose aspirin in women at risk for PE may substantially reduce the prevalence of the disease. Effective screening for PE requiring delivery before 37 weeks (preterm PE) can be provided by a combination of maternal factors, uterine artery Doppler, mean arterial pressure, maternal serum pregnancy-associated plasma protein A and placental growth factor at 11-13 weeks' gestation, with a detection rate of 75% at a false-positive rate of 10%. We present a protocol (V.6, date 25 January 2016) for the ASpirin for evidence-based PREeclampsia prevention (ASPRE) trial, which is a double-blinded, placebo-controlled, randomised controlled trial (RCT) that uses an effective PE screening programme to determine whether low-dose aspirin given to women from 11 to 13 weeks' gestation will reduce the incidence of preterm PE. METHODS AND ANALYSIS: All eligible women attending for their first trimester scan will be invited to participate in the screening study for preterm PE. Those found to be at high risk of developing preterm PE will be invited to participate in the RCT. Further scans will be conducted for assessment of fetal growth and biomarkers. Pregnancy and neonatal outcomes will be collected and analysed. The first enrolment for the pilot study was in April 2014. As of April 2016, 26 670 women have been screened and 1760 recruited to the RCT. The study is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry. TRIAL REGISTRATION NUMBER: ISRCTN13633058. PMID- 27354080 TI - Lumbar intervertebral disc degeneration and related factors in Korean firefighters. AB - OBJECTIVES: The job of firefighting can cause lumbar burden and low back pain. This study aimed to identify the association between age and lumbar intervertebral disc degeneration and whether the association differs between field and administrative (non-field) firefighters. METHODS: Subjects were selected using a stratified random sampling method. Firefighters were stratified by geographic area, gender, age and type of job. First, 25 fire stations were randomly sampled considering regional distribution. Then firefighters were stratified by gender, age and their job and randomly selected among the strata. A questionnaire survey and MRI scans were performed, and then four radiologists used Pfirrmann classification methods to determine the grade of lumbar intervertebral disc degeneration. RESULTS: Pfirrmann grade increased with lumbar intervertebral disc level. Analysis of covariance showed that age was significantly associated with lumbar intervertebral disc degeneration (p<0.05). The value of beta (parameter estimate) was positive at all lumbar intervertebral disc levels and was higher in the field group than in the administrative group at each level. In logistic regression analysis, type of job was statistically significant only with regard to the L4-5 intervertebral disc (OR 3.498, 95% CI 1.241 to 9.860). CONCLUSIONS: Lumbar intervertebral disc degeneration is associated with age, and field work such as firefighting, emergency and rescue may accelerate degeneration in the L4-5 intervertebral disc. The effects of field work on lumbar intervertebral disc degeneration were not clear in discs other than at the level L4-5. PMID- 27354082 TI - Epidemiology of cancers in Lahore, Pakistan, 2010-2012: a cross-sectional study. AB - OBJECTIVES: To estimate the population-level cancer estimates for the Lahore district, which is part of the Punjab Cancer Registry (PCR), Pakistan. The average population per year of Lahore was estimated at 9.8 million in 2010-2012. DESIGN: A cross-sectional study. SETTING: The Registry has 19 collaborating centres in Lahore that report their data to the Central Office located within a tertiary care cancer treatment facility in Lahore, Pakistan. PARTICIPANTS: Patients belonging to Lahore, of any age-group, and diagnosed with cancer in 2010 2012, were included in the study. They were followed up between July and October 2015 to determine their vital status. OUTCOME MEASURES: Summaries were generated for gender, the basis of diagnosis, diagnoses and deaths. The Age-Standardized Incidence Rates (ASIR) were computed per 100 000 population, by gender and cancer site. Five-year age categories were created from 0-4 until 70-74, followed by 75+ years. Death counts were reported by site. RESULTS: Between 2010 and 2012, in Lahore, a total of 15 840 new cancers were diagnosed in 43% male patients and 57% female patients; 93.5% were microscopically confirmed and 6.5% non microscopically. In females, the ASIR was 105.1 and in males, it was 66.7. ASIRs of leading cancers among women were breast 47.6, ovary 4.9 and corpus uteri 3.6, whereas among men they were prostate 6.4, bladder 5.0, and trachea, bronchus and lung 4.6. A total of 5134 deaths were recorded. CONCLUSIONS: In Lahore, the ASIR was higher in women than in men. Among women and men, breast cancer and prostate cancer, respectively, were the leading cancer types. These estimates can be used for health promotion and policymaking in the region. PMID- 27354083 TI - Minority ethnicity patient satisfaction and experience: results of the National Cancer Patient Experience Survey in England. AB - OBJECTIVES: This study sought to explore the differential patient satisfaction reported by patients with cancer who are from ethnic minority backgrounds, examining patient-reported experience of interacting with medical and nursing staff. SETTING: As a secondary analysis, we collated data collected over two consecutive annual rounds of the National Cancer Patient Experience Survey (NCPES) from September 2012 to November 2013. PARTICIPANTS: There were 138 878 responses from 155 hospital trusts across the National Health Service in England, representing a response rate of 63.9% based on the total identified cohort of patients receiving cancer care over those 2 years. OUTCOMES: We used the results of the annual survey, which sought to assess overall patient satisfaction along with patient experience of interacting with clinical nurse specialists, hospital doctors and ward nurses. RESULTS: Ethnic minority patients reported lower satisfaction and less positive experiences of care overall. While some of this difference appeared related to demographic and socioeconomic variation, ethnic minority patients remained less positive than those in the White British group, after statistical adjustment. Ethnic minority patients also reported lower confidence in, and less understanding of, healthcare professionals, including clinical nurse specialists, doctors and ward nurses. CONCLUSIONS: Given the diversity of the British population, as well as the clustering of ethnic minority patients in certain urban areas, a better understanding of the expectations and additional needs of ethnic minority patients is required to improve their experience of and satisfaction with cancer care. PMID- 27354085 TI - Correction: Protocol for an open-label, single-arm trial of HIV pre-exposure prophylaxis (PrEP) among people at high risk of HIV infection: the NSW Demonstration Project PRELUDE. PMID- 27354084 TI - Protocol for the 'Virtual Traveller' cluster-randomised controlled trial: a behaviour change intervention to increase physical activity in primary-school Maths and English lessons. AB - INTRODUCTION: Physical activity (PA) has been shown to be an important factor for health and educational outcomes in children. However, a large proportion of children's school day is spent in sedentary lesson-time. There is emerging evidence about the effectiveness of physically active lessons: integrating physical movements and educational content in the classroom. 'Virtual Traveller' is a novel 6-week intervention of 10-min sessions performed 3 days per week, using classroom interactive whiteboards to integrate movement into primary-school Maths and English teaching. The primary aim of this project is to evaluate the effect of the Virtual Traveller intervention on children's PA, on-task behaviour and student engagement. METHODS AND ANALYSIS: This study will be a cluster randomised controlled trial with a waiting-list control group. Ten year 4 (aged 8 9 years) classes across 10 primary schools will be randomised by class to either the 6-week Virtual Traveller intervention or the waiting-list control group. Data will be collected 5 times: at baseline, at weeks 2 and 4 of the intervention, and 1 week and 3 months postintervention. At baseline, anthropometric measures, 4-day objective PA monitoring (including 2 weekend days; Actigraph accelerometer), PA and on-task behaviour observations and student engagement questionnaires will be performed. All but anthropometric measures will be repeated at all other data collection points. Changes in overall PA levels and levels during different time periods (eg, lesson-time) will be examined. Changes in on-task behaviour and student engagement between intervention groups will also be examined. Multilevel regression modelling will be used to analyse the data. Process evaluation will be carried out during the intervention period. ETHICS AND DISSEMINATION: The results of this study will be disseminated through peer-review publications and conference presentations. Ethical approval was obtained through the University College London Research Ethics Committee (reference number: 3500-004). PMID- 27354086 TI - PReventing early unplanned hOspital readmission aFter critical ILlnEss (PROFILE): protocol and analysis framework for a mixed methods study. AB - INTRODUCTION: Survivors of critical illness experience multidimensional disabilities that reduce quality of life, and 25-30% require unplanned hospital readmission within 3 months following index hospitalisation. We aim to understand factors associated with unplanned readmission; develop a risk model to identify intensive care unit (ICU) survivors at highest readmission risk; understand the modifiable and non-modifiable readmission drivers; and develop a risk assessment tool for identifying patients and areas for early intervention. METHODS AND ANALYSIS: We will use mixed methods with concurrent data collection. Quantitative data will comprise linked healthcare records for adult Scottish residents requiring ICU admission (1 January 2000-31 December 2013) who survived to hospital discharge. The outcome will be unplanned emergency readmission within 90 days of index hospital discharge. Exposures will include pre-ICU demographic data, comorbidities and health status, and critical illness variables representing illness severity. Regression analyses will be used to identify factors associated with increased readmission risk, and to develop and validate a risk prediction model. Qualitative data will comprise recorded/transcribed interviews with up to 60 patients and carers recently experiencing unplanned readmissions in three health board regions. A deductive and inductive thematic analysis will be used to identify factors contributing to readmissions and how they may interact. Through iterative triangulation of quantitative and qualitative data, we will develop a construct/taxonomy that captures reasons and drivers for unplanned readmission. We will validate and further refine this in focus groups with patients/carers who experienced readmissions in six Scottish health board regions, and in consultation with an independent expert group. A tool will be developed to screen for ICU survivors at risk of readmission and inform anticipatory interventions. ETHICS AND DISSEMINATION: Data linkage has approval but does not require ethical approval. The qualitative study has ethical approval. Dissemination with key healthcare stakeholders and policymakers is planned. TRIAL REGISTRATION NUMBER: UKCRN18023. PMID- 27354088 TI - Vulnerability of the peatland carbon sink to sea-level rise. AB - Freshwater peatlands are carbon accumulating ecosystems where primary production exceeds organic matter decomposition rates in the soil, and therefore perform an important sink function in global carbon cycling. Typical peatland plant and microbial communities are adapted to the waterlogged, often acidic and low nutrient conditions that characterise them. Peatlands in coastal locations receive inputs of oceanic base cations that shift conditions from the environmental optimum of these communities altering the carbon balance. Blanket bogs are one such type of peatlands occurring in hyperoceanic regions. Using a blanket bog to coastal marsh transect in Northwest Scotland we assess the impacts of salt intrusion on carbon accumulation rates. A threshold concentration of salt input, caused by inundation, exists corresponding to rapid acidophilic to halophilic plant community change and a carbon accumulation decline. For the first time, we map areas of blanket bog vulnerable to sea-level rise, estimating that this equates to ~7.4% of the total extent and a 0.22 Tg yr(-1) carbon sink. Globally, tropical peatlands face the proportionally greatest risk with ~61,000 km(2) (~16.6% of total) lying <=5 m elevation. In total an estimated 20.2 +/- 2.5 GtC is stored in peatlands <=5 m above sea level, which are potentially vulnerable to inundation. PMID- 27354087 TI - A qualitative study on becoming cared for in Alzheimer's disease: the effects to women's sense of identity. AB - OBJECTIVE: To explore the lived experience of becoming cared for and the impact this has on the identity and sense of self of women with Alzheimer's disease. METHOD: Eight women with mild-to-moderate Alzheimer's disease were interviewed in Northamptonshire, England, on two separate occasions about their experiences relating to needing assistance with instrumental activities of daily living (IADL) tasks. Interpretative phenomenological analysis was the approach used to underpin this research. RESULTS: Changes in the women's identity affected by the increased need for assistance with IADL tasks were expressed in terms of: who I am; unhappy being me; fighting to remain me; I'm not the same, but it doesn't worry me; and acceptance and contentment. CONCLUSION: This study offers an alternative perspective to the view that all women with Alzheimer's disease experience becoming cared for as a negative event in their lives. Some factors universally perceived as being a result of Alzheimer's disease may be a normal part of the life course. PMID- 27354089 TI - 3D Facial Effects of a Simulated Dental Build-up. AB - OBJECTIVE: The purpose of this study was to evaluate the 3D-stereophotogrammetry technique to detect differences in facial appearance after a simulated rehabilitation. MATERIALS AND METHODS: Eleven volunteers without tooth wear participated. A 3D-stereophotograph was taken in five different situations: resting position, teeth in occlusion, and teeth in occlusion with a 1 mm-, 3 mm- or 5 mm resin block between the first molars. Cephalometric measurements were performed on the 3D-stereophotographs using the software program Maxilim(r) (Medicim NV Mechelen, Belgium). Four anatomical parameters were analyzed: (1) Subnasale-Gnathion, (2) Subnasale-Stomion, (3) Stomion-Gnathion, and (4) Masseter right-Masseter left. A paired Student's T-test was applied to detect significant differences (p < 0.05). RESULTS: Statistically significant changes in facial appearance of the lower facial height were detected in all measured positions, teeth in occlusion, 1 mm-, 3 mm-, and 5 mm block (p < 0.05). For the main distance (Subnasale-Gnathion) the mean measured differences were, respectively, 3.2 mm; 5.2 mm; and 6.7 mm. CONCLUSIONS: With 3D-stereophotograph imaging technology, it was possible to detect changes in facial appearance after an artificial increase of vertical dimension of occlusion. This finding implies that reconstruction of loss of tooth substance may cause a visible change in facial appearance of the patient. CLINICAL SIGNIFICANCE: This study reveals a new 3D imaging technique that may be used for a better and more comprehensive treatment planning in patients with severe tooth wear. (J Esthet Restor Dent 28:397-404, 2016). PMID- 27354090 TI - Two meals with different carbohydrate, fat and protein contents render equivalent postprandial plasma levels of calprotectin, cortisol, triglycerides and zonulin. AB - The aim was to compare postprandial plasma levels of calprotectin, cortisol, triglycerides and zonulin between a control breakfast and a moderately low carbohydrate test breakfast, given randomly after 10-h fast. Blood samples were collected before and repeatedly after the meal. Plasma calprotectin, cortisol, triglycerides and zonulin were analyzed. The total area under the curve (tAUC) and change in AUC from baseline (dAUC) were calculated. Ratios between the test and control values were calculated to investigate equivalence. Healthy volunteers (8 men and 12 women; 46.0 +/- 14.5 years) were included. tAUCs of cortisol and triglycerides did not differ between the breakfasts (p = 0.158 versus p = 0.579). Cortisol dAUCs were decreased and triglyceride dAUCs were increased after both breakfasts, with no differences between the breakfasts (p = 0.933 versus p = 0.277). Calprotectin and zonulin levels were unaffected. The meals were bioequivalent for cortisol, triglycerides and zonulin, but not for calprotectin. PMID- 27354091 TI - NOS knockout or inhibition but not disrupting PSD-95-NOS interaction protect against ischemic brain damage. AB - Promising results have been reported in preclinical stroke target validation for pharmacological principles that disrupt the N-methyl-D-aspartate receptor-post synaptic density protein-95-neuronal nitric oxide synthase complex. However, post synaptic density protein-95 is also coupled to potentially neuroprotective mechanisms. As post-synaptic density protein-95 inhibitors may interfere with potentially neuroprotective mechanisms and sufficient validation has often been an issue in translating basic stroke research, we wanted to close that gap by comparing post-synaptic density protein-95 inhibitors with NOS1(-/-) mice and a NOS inhibitor. We confirm the deleterious role of NOS1 in stroke both in vivo and in vitro, but find three pharmacological post-synaptic density protein-95 inhibitors to be therapeutically ineffective. PMID- 27354092 TI - Quantitative T1 mapping under precisely controlled graded hyperoxia at 7T. AB - Increasing the concentration of oxygen dissolved in water is known to increase the recovery rate (R1 = 1/T1) of longitudinal magnetization (T1 relaxation). Direct T1 changes in response to precise hyperoxic gas challenges have not yet been quantified and the actual effect of increasing arterial oxygen concentration on the T1 of brain parenchyma remains unclear. The aim of this work was to use quantitative T1 mapping to measure tissue T1 changes in response to precisely targeted hyperoxic respiratory challenges ranging from baseline end-tidal oxygen (PetO2) to approximately 500 mmHg. We did not observe measureable T1 changes in either gray matter or white matter parenchymal tissue. The T1 of peripheral cerebrospinal fluid located within the sulci, however, was reduced as a function of PetO2. No significant T1 changes were observed in the ventricular cerebrospinal fluid under hyperoxia. Our results indicate that care should be taken to distinguish actual T1 changes from those which may be related to partial volume effects with cerebrospinal fluid, or regions with increased fluid content such as edema when examining hyperoxia-induced changes in T1 using methods based on T1-weighted imaging. PMID- 27354093 TI - Evaluation of [18F]MC225 as a PET radiotracer for measuring P-glycoprotein function at the blood-brain barrier in rats: Kinetics, metabolism, and selectivity. AB - P-glycoprotein is a protective efflux transporter at the blood-brain barrier showing altered function in many neurological disorders. The purpose of this study was to validate [18F]MC225 as a radiotracer for measuring P-glycoprotein function with positron emission tomography. Three groups of Sprague-Dawley rats were used to assess tracer uptake at baseline (group 1), after inhibition of P glycoprotein (group 2), and after inhibition of both P-glycoprotein and breast cancer resistance protein (Bcrp, group 3). A two-tissue compartment model with a metabolite-corrected plasma input function provided the best fit to the positron emission tomography data, but parameter estimates were more reliable in a one tissue compartment model, which was selected as the preferred model. Regional distribution volumes ( VT) in the control group ranged from 6 to 11, which is higher than for other radiotracers. [18F]MC225 showed transporter selectivity, since inhibition of P-glycoprotein caused a two to fourfold increase in the cerebral VT values, but additional inhibition of Bcrp did not cause any further increase. Metabolic stability of [18F]MC225 was moderate (at 1 h post-injection 15% of plasma radioactivity and 76% of brain radioactivity represented intact parent). Thus, [18F]MC225 may be a useful radiotracer to measure especially increases of P-glycoprotein function at the blood-brain barrier. PMID- 27354094 TI - Amylin alters human brain pericyte viability and NG2 expression. AB - Amylin, a pancreatic beta-cell-derived peptide hormone, forms inclusions in brain microvessels of patients with dementia who have been diagnosed with type 2 diabetes and Alzheimer's disease. The cellular localization of these inclusions and the consequences thereof are not yet known. Using immunohistochemical staining of hippocampus and parahippocampal cortex from patients with Alzheimer's disease and non-demented controls, we show that amylin cell inclusions are found in pericytes. The number of amylin cell inclusions did not differ between patients with Alzheimer's disease and controls, but amylin-containing pericytes displayed nuclear changes associated with cell death and reduced expression of the pericyte marker neuron-glial antigen 2. The impact of amylin on pericyte viability was further demonstrated in in vitro studies, which showed that pericyte death increased in presence of fibril- and oligomer amylin. Furthermore, oligomer amylin increased caspase 3/7 activity, reduced lysate neuron-glial antigen 2 levels and impaired autophagy. Our findings contribute to increased understanding of how aggregated amylin affects brain vasculature and highlight amylin as a potential factor involved in microvascular pathology in dementia progression. PMID- 27354096 TI - Evidence for a "metabolically inactive" inorganic phosphate pool in adenosine triphosphate synthase reaction using localized 31P saturation transfer magnetic resonance spectroscopy in the rat brain at 11.7 T. AB - With the increased spectral resolution made possible at high fields, a second, smaller inorganic phosphate resonance can be resolved on (31)P magnetic resonance spectra in the rat brain. Saturation transfer was used to estimate de novo adenosine triphosphate synthesis reaction rate. While the main inorganic phosphate pool is used by adenosine triphosphate synthase, the second pool is inactive for this reaction. Accounting for this new pool may not only help us understand (31)P magnetic resonance spectroscopy metabolic profiles better but also better quantify adenosine triphosphate synthesis. PMID- 27354098 TI - An event-related potential investigation of pattern separation and pattern completion processes. AB - Long-term declarative memory depends on pattern separation and pattern completion to maintain memory specificity. Previous studies aimed at evaluating the underlying neuronal substrates of these computational processes have used a mnemonic discrimination paradigm and functional magnetic resonance imaging (fMRI). An alternative method is electroencephalography and event-related potentials (ERPs), which have a superior time resolution to fMRI. Here, we use ERP analysis to examine neuronal activity during performance of a mnemonic discrimination task. We examined both the late positive component and FN400 components, which have previously been shown to demonstrate an old-new effect. We hypothesized that pattern separation processes would be reflected in correct rejection of similar lures while pattern completion processes would be reflected in falsely categorizing lures as repeated. We did not observe differences between the ERPs associated with these two processes. PMID- 27354097 TI - Mother-Child Interaction: Links Between Mother and Child Frontal Electroencephalograph Asymmetry and Negative Behavior. AB - It is well accepted that parent-child interactions are bidirectional by nature, yet not much is known about the psychophysiological activity underlying these interactions. This study examined, during a parent-child interaction, how a child's negativity statistically predicted maternal frontal electroencephalograph (EEG) asymmetry and how a mother's negativity statistically predicted child frontal EEG asymmetry. Thirty-four mother-child dyads participated in the study. Maternal and child behaviors and physiology were measured during a puzzle task. Results indicated that mothers whose children exhibited more challenging behaviors during the dyadic interaction displayed more right (relative to left) asymmetry, as did children whose mothers were high in negativity during the interaction. These findings suggest that mothers and children react to each other's signals not only behaviorally but also physiologically. PMID- 27354099 TI - Addressing the continuum of maternal and newborn care in Ghana: implications for policy and practice. AB - Although the past decade has brought global reductions in maternal, infant and child mortality, many low-resource settings have failed to make significant gains relative to their high-income counterparts. In Ghana, nearly 50% of under-five mortality in 2014 could be attributed to deaths during the first 28 days after birth. This article analyses the data across a mixed-methods study of the factors impacting maternal and neonatal care in northern Ghana. The stillbirth and neonatal death study (SANDS) was conducted in 2010 and included both quantitative (N = 20 497) and qualitative data collection (N = 253) to explore the issues associated with the continuum of reproductive health care. Findings were compared against an adaptation of the WHO/UNICEF framework for integrated maternal and newborn care and used to generate concrete recommendations for clinicians, policymakers and programmers across the continuum of care, from pregnancy through delivery and postnatal care. SANDS elucidated epidemiological trends: 40% of neonatal deaths occurred on the first day after birth, and the leading causes of early neonatal mortality were birth asphyxia/injury, infection and complications of prematurity. Qualitative data reflect findings along two axes-community to facility-based care, and pre-pregnancy through the postnatal period. Resulting recommendations include the need to improving clinicians' understanding of and sensitization to local traditional practices, the need for policies to better address quality of care and coordination of training efforts, and the need for comprehensive, integrated programmes that ensure continuity of care from pre pregnancy through the post-partum period. SANDS illustrates complex medical social-cultural knowledge, attitudes and practices that span the reproductive period in rural northern Ghana. Data illustrate that not only are the first few days of life critical in infant survival but also there are significant social and cultural barriers to ensuring that mothers and their newborns are cared for in a timely, evidence-based manner. PMID- 27354100 TI - Experiences of discrimination and positive treatment from health professionals: A national survey of adults with mental health problems. AB - OBJECTIVE: To systematically investigate the scope and nature of discrimination and positive treatment experienced by adults with mental health problems when using health services in an Australian population-based survey. METHODS: Australian adults (n = 1381) who reported a mental health problem or scored high on a screening questionnaire were interviewed about their experience of discrimination and positive treatment from healthcare professionals. Descriptions of experiences were content-analysed to identify key characteristics. RESULTS: In all, 11.8% of respondents reported discrimination from a health professional in the past 12 months. The most common types of discrimination included being treated dismissively, being judged and not being listened to, particularly regarding personal history and treatment needs. In contrast, 40.4% reported being treated more positively by their health professional because of their mental health problem. Key types of positive treatment by health professionals were being supportive and understanding and being a good listener. Good quality care approaches were also appreciated, including making a referral, being engaged in the treatment process, regularly checking the status of the person's mental health and providing information. CONCLUSION: A minority of respondents with mental health problems had experienced discrimination from their healthcare professional, potentially interfering with recovery. Anti-stigma education interventions for healthcare professionals should address how to increase knowledge and understanding of mental health problems, reduce negative attitudes and encourage supportive behaviours. PMID- 27354095 TI - 'Spreading depression of Leao' and its emerging relevance to acute brain injury in humans. AB - A new research field in translational neuroscience has opened as a result of the recognition since 2002 that "spreading depression of Leao" can be detected in many patients with acute brain injury, whether vascular and spontaneous, or traumatic in origin, as well as in those many individuals experiencing the visual (or sensorimotor) aura of migraine. In this review, we trace from their first description in rabbits through to their detection and study in migraine and the injured human brain, and from our personal perspectives, the evolution of understanding of the importance of spread of mass depolarisations in cerebral grey matter. Detection of spontaneous depolarisations occurring and spreading in the periphery or penumbra of experimental focal cortical ischemic lesions and of their adverse effects on the cerebral cortical microcirculation and on the tissue glucose and oxygen pools has led to clearer concepts of how ischaemic and traumatic lesions evolve in the injured human brain, and of how to seek to improve clinical management and outcome. Recognition of the likely fundamental significance of spreading depolarisations for this wide range of serious acute encephalopathies in humans provides a powerful case for a fresh examination of neuroprotection strategies. PMID- 27354101 TI - Gastric pancreatic heterotopia with pancreatic intraepithelial neoplasia. PMID- 27354102 TI - Gastric per-oral endoscopic myotomy for refractory gastroparesis: results from the first multicenter study on endoscopic pyloromyotomy (with video). AB - BACKGROUND AND AIMS: Gastric per-oral endoscopic myotomy (G-POEM) recently has been reported as minimally invasive therapy for gastroparesis. The aims of this study were to report on the first multicenter experience with G-POEM and to assess the efficacy and safety of this novel procedure for patients with gastroparesis with symptoms refractory to medical therapy. METHODS: All patients with gastroparesis who underwent endoscopic pyloromyotomy (G-POEM) at 5 medical centers were included. Procedures were performed following the same principles as esophageal POEM. Clinical response was defined as improvement in gastroparetic symptoms with absence of recurrent hospitalization. Adverse events were graded according to the American Society for Gastrointestinal Endoscopy lexicon. RESULTS: A total of 30 patients with refractory gastroparesis (11 diabetic, 12 postsurgical, 7 idiopathic) underwent G-POEM. Previous therapies included Botox injection in 12, transpyloric stenting in 3, and PEG with jejunal extension (PEGJ) in 1. Nausea/vomiting were the predominant symptoms in 25 patients. Weight loss was present in 27 patients with an average of 10% loss of body weight. G POEM was completed successfully in all 30 (100%) patients with a mean procedure time of 72 minutes (range, 35-223 min). The mean myotomy length was 2.6 +/- 2.3 cm. The mean length of hospital stay was 3.3 days (range, 1-12 days). Two adverse events occurred in 2 (6.7%) patients, including 1 capnoperitoneum and 1 prepyloric ulcer, rated as mild and severe, respectively. Clinical response was observed in 26 (86%) patients during a median follow-up of 5.5 months. Four patients (2 diabetic, 1 postsurgical, 1 idiopathic cause) did not respond to G POEM. Repeat gastric emptying scan was obtained in 17 patients, normalized in 8 (47%), and improved in 6 (35%) patients. CONCLUSION: G-POEM is a technically feasible procedure. This small non-randomized study suggests the effectiveness of G-POEM for the treatment of patients with gastroparesis refractory to medical therapy. It concomitantly results in normalization of GES in a significant proportion of treated patients. PMID- 27354103 TI - A case of intragastric wall abscess developing after EUS-FNA in a patient with pancreatic body cancer. PMID- 27354104 TI - Use of sequential endorectal US to predict the tumor response of preoperative chemoradiotherapy in rectal cancer. AB - BACKGROUND AND AIMS: Accurate prediction of the response to preoperative chemoradiotherapy (CRT) potentially assists in the individualized selection of treatment. Endorectal US (ERUS) is widely used for the pretreatment staging of rectal cancer, but its use for preoperatively predicting the effects of CRT is not well evaluated because of the inflammation, necrosis, and fibrosis induced by CRT. This study assessed the value of sequential ERUS in predicting the efficacy of preoperative CRT for locally advanced rectal cancer. METHODS: Forty-one patients with clinical stage II/III rectal adenocarcinoma were enrolled prospectively. Radiotherapy was delivered to the pelvis with concurrent chemotherapy of capecitabine and oxaliplatin. Total mesorectal excision was performed 6 to 8 weeks later. EUS measurements of primary tumor maximum diameter were performed before (ERUS1), during (ERUS2), and 6 to 8 weeks after (ERUS3) CRT, and the ratios of these were calculated. Correlations between ERUS values, tumor regression grade (TRG), T down-staging rate, and pathologic complete response (pCR) rate were assessed, and survival was analyzed. RESULTS: There was no significant correlation between ERUS2/ERUS1 and TRG. The value of ERUS3/ERUS1 correlated with pCR rate and TRG but not T down-staging rate. An ERUS3 value of 6.3 mm and ERUS3/ERUS1 of 52% were used as the cut-off for predicting pCR, and patients were divided into good and poor prognosis groups. Although not statistically significant, 3-year recurrence and survival rates of the good prognosis group were better than those of the poor prognosis group. CONCLUSIONS: Sequential ERUS may predict therapeutic efficacy of preoperative CRT for locally advanced rectal cancer. (Clinical trial registration number: NCT01582750.). PMID- 27354105 TI - Classic Spotlight: Molecular Biology of Methicillin Resistance in Staphylococcus aureus. PMID- 27354106 TI - Classic Spotlight: Bacterial Endospore Resistance, Structure, and Genetics. PMID- 27354109 TI - Ecological determinants of mean family age of angiosperm trees in forest communities in China. AB - Species assemblage in a local community is determined by the interplay of evolutionary and ecological processes. The Tropical Niche Conservatism hypothesis proposes mechanisms underlying patterns of biodiversity in biological communities along environmental gradients. This hypothesis predicts that, among other things, clades in areas with warm or wet environments are, on average, older than those in areas with cold or dry environments. Focusing on angiosperm trees in forests, this study tested the age-related prediction of the Tropical Niche Conservatism hypothesis. We related the mean family age of angiosperm trees in 57 local forests from across China with 23 current and paleo-environmental variables, which included all major temperature- and precipitation-related variables. Our study shows that the mean family age of angiosperm trees in local forests was positively correlated with temperature and precipitation. This finding is consistent with the age-related prediction of the Tropical Niche Conservatism hypothesis. Approximately 85% of the variance in the mean family age of angiosperm trees was explained by temperature-related variables, and 81% of the variance in the mean family age of angiosperm trees was explained by precipitation-related variables. Climatic conditions at the Last Glacial Maximum did not explain additional variation in mean family age after accounting for current environmental conditions. PMID- 27354110 TI - Internationally educated nurses' reflections on nursing communication in Canada. AB - AIM: The overall goal of this study was to explore internationally educated nurses' perceptions of the English language and nursing communication skill requirements in a Canadian bridging education program. BACKGROUND: The increased global mobility of nurses creates a need to address the educational needs of migrating nurses. A large percentage of these nurses require additional language and professional education. New research is needed that would represent an in depth analysis of their educational experiences associated with learning academic English and Canadian nursing communication. INTRODUCTION: Developing proficiency with a new language has been documented as posing challenges for new immigrants. Since language proficiency is a key requirement of Canadian nursing regulatory bodies, previously unrecognized barriers such as attitudes and beliefs about required English language and nursing communication competency which may hinder their ability to meet local practice standards need to be explored. METHOD: Using a grounded theory study design, narratives from 22 participants from the Philippines, Nigeria and Europe enrolled in bridging education were collected and analysed. RESULTS: The participants identified the incongruence in professional norms between Canada and their home country as a major challenge. The major themes identified included cultural dissonance, academic literacy challenges and skepticism regarding unexpected communication competency requirements. DISCUSSION: The participants possessed varying degrees of comprehension and acceptance of new educational and professional regulatory requirements. A certain degree of culture shock, which may be associated with frustration and disillusionment, is a typical and anticipated aspect of the immigration process. Their perceptions need to be recognized and accommodated when assisting internationally educated nurses to integrate into the Canadian practice culture. LIMITATIONS OF THE STUDY: Any generalizations to other host countries need to be made cautiously. CONCLUSION AND IMPLICATIONS FOR NURSING POLICY: Clear communication from regulators about English language and nursing communication requirements during the pre-arrival period is recommended. If bridging education is required, these programs need to be designed to address English language competency and nursing communication skills of non-native English speakers. PMID- 27354111 TI - Giving the Help That Is Needed: How Regulatory Mode Impacts Social Support. AB - Social support is most effective when it meets recipients' needs. Guided by regulatory mode theory, this article examines how support providers' chronic motivational concerns with assessment and locomotion shape help provision. We hypothesized that stronger assessment concerns motivate helpers to "tailor" support efforts by offering support that meets helpees' specific motivational concerns and not offering support that would fail to address these concerns. In contrast, we predicted that stronger locomotion concerns motivate helpers to offer both support that fits helpees' needs and support that does not. The results of Studies 1 and 2, using hypothetical scenarios, were consistent with these hypotheses. Study 3 replicated these findings in support interactions among friend pairs, and also found that helper assessment predicted greater support tailoring, which in turn predicted helpees' negative mood improvement. Chronic assessment and locomotion concerns direct support efforts and influence the extent to which support is beneficial. PMID- 27354112 TI - Stacking the Jury: Legal Professionals' Peremptory Challenges Reflect Jurors' Levels of Implicit Race Bias. AB - Most legal systems are based on the premise that defendants are treated as innocent until proven guilty and that decisions will be unbiased and solely based on the facts of the case. The validity of this assumption has been questioned for cases involving racial minority members, in that racial bias among jury members may influence jury decisions. The current research shows that legal professionals are adept at identifying jurors with levels of implicit race bias that are consistent with their legal interests. Using a simulated voir dire, professionals assigned to the role of defense lawyer for a Black defendant were more likely to exclude jurors with high levels of implicit race bias, whereas prosecutors of a Black defendant did the opposite. There was no relation between professionals' peremptory challenges and jurors' levels of explicit race bias. Implications for the role of racial bias in legal decision making are discussed. PMID- 27354113 TI - Unveiling the oxidative metabolism of Rhipicephalus microplus (Acari: Ixodidae) experimentally exposed to entomopathogenic fungi. AB - Rhipicephalus microplus is an important tick in tropical regions due to the high economic losses caused by its parasitism. Metarhizium anisopliae and Beauveria bassiana are well-known entomopathogenic fungi that can afflict R. microplus ticks. The development of new targets and strategies to control this parasite can be driven by studies of this tick's physiology. Recently, it was reported that when exposed to adverse physiological conditions, ticks can activate fermentative pathways, indicating transition from aerobic to anaerobic metabolism. Nevertheless, the precise mechanism by which entomopathogenic fungi influence R. microplus metabolism has not been clarified, limiting understanding of the tick fungus association. Thus, the present study aimed to evaluate the effect of infection of ticks by M. anisopliae and B. bassiana on the amount of selected carboxylic acids present in the hemolymph, enabling increased understanding of changes previously reported. The results showed preservation in the concentrations of oxalic, lactic, and pyruvic acids in the hemolymph 24 and 48 h after dropping from cattle; while there were variations in the concentration of these carboxylic acids after infection of female ticks to M. anisopliae and B. bassiana. Significant increases were observed in the concentration of oxalic and lactic acids and significant reduction of pyruvic acid for both observation times (24 and 48 h) after infection by entomopathogenic fungi. These results indicate that B. bassiana and M. anisopliae infection alters the basal metabolism of R. microplus females, resulting in the activation of fermentative pathways. PMID- 27354114 TI - Anemia in pregnant adolescents: impact of treatment on perinatal outcomes. AB - OBJECTIVE: This study sought to evaluate the anemia prevalence and effect of anemia treatment in pregnant adolescents. METHODS: A cross-sectional study. Data from perinatal outcomes, serum hemoglobin level and iron supplementation were collected. Samples were divided into three groups: pregnant adolescents without anemia, with treated anemia and with untreated anemia. Frequencies, means, standard deviations and Chi-squared values were calculated. The significance level was 5%, and the software used was Epi-info 7. RESULTS: The study included 458 pregnant adolescents. The mean age was 16 years old, and the prevalence of anemia was 41.27% (189). Mild, moderate or severe anemia were presented in 65.60%, 33.86% and 0.52%, respectively, of study participants. Among pregnant adolescents with anemia, 87.24% received treatment with iron supplementation. Preterm labor (p = 0.003), gestational age at birth <37 weeks (p = 0.036) and stillbirth (p = 0.004) showed an association with nontreated anemia. Positive HIV was more prevalent in adolescents with nontreated anemia (p = 0.018). The cesarean rate was 36.90%, with no difference between groups. CONCLUSION: Anemia is a public health problem among pregnant adolescents, and iron supplementation reduces negative neonatal outcomes. Treatment adherence by a multidisciplinary and qualified prenatal care team can be key in reducing adverse neonatal outcomes associated with pregnancy during adolescence. PMID- 27354115 TI - CD101: a novel long-acting echinocandin. AB - CD101 is a novel echinocandin drug being developed to treat severe fungal infections including invasive candidiasis. We have performed a series of studies to evaluate the antifungal properties of CD101 against both echinocandin susceptible and -resistant Candida strains. Antifungal susceptibility testing performed on a collection of 95 Candida strains including 30 caspofungin resistant isolates containing fks mutations demonstrated comparable antifungal potency of CD101 relative to micafungin (MCF) across different Candida species. Comparable kinetic inhibition of glucan synthase activity was also observed for CD101 and MCF on both wild-type (WT) and resistant fks mutant Candida strains. Similarly, both drugs yielded nearly identical values for a mutant prevention concentration. In a murine model of invasive candidiasis, CD101 displayed better or at least comparable efficacy relative to MCF in treating WT or fks mutant Candida albicans. An exceptional long-lived pharmacokinetic profile was observed in mice following a single dose of CD101. Collectively, CD101 has great potential not only in treating invasive Candida infections but also in preventing emergence of resistance to currently approved echinocandin drugs. PMID- 27354116 TI - Global regulation of alternative RNA splicing by the SR-rich protein RBM39. AB - BACKGROUND: RBM39 is a serine/arginine-rich RNA-binding protein that is highly homologous to the splicing factor U2AF65. However, the role of RBM39 in alternative splicing is poorly understood. METHODS: In this study, RBM39-mediated global alternative splicing was investigated using RNA-Seq and genome-wide RBM39 RNA interactions were mapped via cross-linking and immunoprecipitation coupled with deep sequencing (CLIP-Seq) in wild-type and RBM39-knockdown MCF-7 cells. RESULTS: RBM39 was involved in the up- or down-regulation of the transcript levels of various genes. Hundreds of alternative splicing events regulated by endogenous RBM39 were identified. The majority of these events were cassette exons. Genes containing RBM39-regulated alternative exons were found to be linked to G2/M transition, cellular response to DNA damage, adherens junctions and endocytosis. CLIP-Seq analysis showed that the binding site of RBM39 was mainly in proximity to 5' and 3' splicing sites. Considerable RBM39 binding to mRNAs encoding proteins involved in translation was observed. Of particular importance, ~20% of the alternative splicing events that were significantly regulated by RBM39 were similarly regulated by U2AF65. CONCLUSIONS: RBM39 is extensively involved in alternative splicing of RNA and helps regulate transcript levels. RBM39 may modulate alternative splicing similarly to U2AF65 by either directly binding to RNA or recruiting other splicing factors, such as U2AF65. GENERAL SIGNIFICANCE: The current study offers a genome-wide view of RBM39's regulatory function in alternative splicing. RBM39 may play important roles in multiple cellular processes by regulating both alternative splicing of RNA molecules and transcript levels. PMID- 27354117 TI - Plant Elongator-mediated transcriptional control in a chromatin and epigenetic context. AB - Elongator (Elp) genes were identified in plants by the leaf growth-altering elo mutations in the yeast (Saccharomyces cerevisiae) gene homologs. Protein purification of the Elongator complex from Arabidopsis thaliana cell cultures confirmed its conserved structure and composition. The Elongator function in plant growth, development, and immune response is well-documented in the elp/elo mutants and correlated with the histone acetyl transferase activity of the ELP3/ELO3 subunit at the coding part of key regulatory genes of developmental and immune response pathways. Here we will focus on additional roles in transcription, such as the cytosine demethylation activity of ELP3/ELO3 at gene promoter regions and primary microRNA transcription and processing through the ELP2 subunit interaction with components of the small interference RNA machinery. Furthermore, specific interactions and upstream regulators support a role for Elongator in transcription and might reveal mechanistic insights into the specificity of the histone acetyl transferase and cytosine demethylation activities for target genes. PMID- 27354118 TI - The oral CRTh2 antagonist QAW039 (fevipiprant): A phase II study in uncontrolled allergic asthma. AB - BACKGROUND: There is an unmet medical need for allergic asthma patients who are uncontrolled on conventional therapies. The aim of this study was to collect efficacy and safety data for QAW039, an oral chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) receptor antagonist, for the treatment of asthma. METHODS: This was an exploratory phase II, double-blind, randomized, placebo-controlled multi-center study. Patients with mild-to-moderate uncontrolled allergic asthma (N = 170) were either without or weaned off inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) and randomized (1:1) to QAW039 (500 mg once daily) or to placebo for 28 days. RESULTS: Overall, 157 patients completed the study. There were no significant differences between QAW039 and placebo for trough forced expiratory volume in 1 s (FEV1) or Asthma control questionnaire (ACQ) in the total population. Subgroup analyses demonstrated that patients with a FEV1 <70% of predicted at baseline treated with QAW039 had significant improvement compared with placebo in trough FEV1 (QAW039- Placebo [Delta] = 207 mL; 90% confidence interval [CI]: 96, 319; P = 0.002) and ACQ7 (Delta = -0.41; 90%CI: -0.69, -0.13; P = 0.009). QAW039 reached a mean maximum concentration (Cmax) of 3440 ng/mL on day 28 at a median Tmax of 1 h (range 0.5-4 h). Most adverse events (AEs) were mild/moderate and balanced between both groups, with no serious AEs. CONCLUSIONS: In the general study population, no improvement in lung function was observed with QAW039. However, a subgroup analysis revealed that patients with greater severity of airflow limitation (FEV1 < 70%) had improved lung function and asthma control when treated with QAW039. QAW039 also demonstrated a favorable safety profile. TRIALS REGISTRATION: ClinicalTrials.govNCT01253603. PMID- 27354119 TI - Synchronous endometrioid adenocarcinomas in the uterine cervix and corpus. AB - It is frequently difficult to distinguish multiple primary carcinomas from single primary carcinoma with metastasis. Here, we report a case of synchronous endometrioid adenocarcinomas that independently occurred in the uterine cervix and corpus. A 47-year-old woman complaining of genital bleeding was preoperatively diagnosed with cervical adenocarcinoma with an endometrial lesion. On surgical treatment, two separate malignant lesions bearing endometrioid adenocarcinoma were identified in the uterine cervix and cavity. Although both lesions expressed the same type of human papillomavirus (HPV) gene, type 16, microscopic continuity was not observed. Furthermore, we detected a critical difference in PTEN mutation between the tumors and finally diagnosed this case as multiple primary cancers. This is the first report to show multiple primary endometrioid adenocarcinomas simultaneously arising in the uterine cervix and corpus. Considering the rarity of this case, the coexistence of HPV suggests its possible involvement in the carcinogenesis of the endometrioid adenocarcinomas. PMID- 27354120 TI - A Critical Appraisal of Growth Hormone Therapy in Growth Hormone Deficiency and Turner Syndrome Patients in Turkey. AB - Early detection of abnormal growth, identification of the underlying cause, and appropriate treatment of the medical condition is an important issue for children with short stature. Growth hormone (GH) therapy is widely used in GH-deficient children and also in non-GH-deficient short stature cases who have findings conforming to certain indications. Efficacy of GH therapy has been shown in a multitude of short- and long-term studies. Age at onset of GH therapy is the most important factor for a successful treatment outcome. Optimal dosing is also essential. The aim of this review was to focus on challenges in the early diagnosis and appropriate management of short stature due to GH deficiency (GHD) and Turner syndrome. These are the most frequent two indications for GH therapy in Turkey approved by the Ministry of Health for coverage by the national insurance system. PMID- 27354121 TI - Structural modeling of tumor necrosis factor: A protein of immunological importance. AB - Tumor necrosis factor (TNF) is a multifunctional pro-inflammatory cytokine responsible for various immunoregulatory activities. Upon binding with its receptor, TNF triggers multiple complex signaling pathways such as the activations of nuclear factor kappa B and caspase cascade, which are the leading determining factors for cell survival or cell death. The present work studies certain modeling aspects of the TNF, with comparative structural analyses of the wild and mutant types of this protein. Additionally, nanoscale molecular dynamics simulations are performed to assess the structure-property relationships of proteins as functions of time. PMID- 27354122 TI - Incidental emotions influence risk preference and outcome evaluation. AB - Incidental emotions, which are irrelevant to the current decision, play a significant role in the decision-making process. In this study, to investigate the influence of incidental emotions on behavioral, psychological, and electrophysiological responses in the process of decision making, participants were required to perform a monetary gambling task. During the selection stage, an emotional picture, which was chosen from the Chinese Affective Picture System and fell into one of three categories: negative, neutral, and positive, was presented between two alternatives (small/large amount of bet). The pictures were provided to induce incidental emotions. ERPs and self-rating emotional experiences to outcome feedback were recorded during the task. Behavioral results showed that positive incidental emotions elicited risk preference, but emotional experiences to outcome feedback were not influenced by incidental emotions. The feedback related negativity amplitudes were larger in the positive emotion condition than in the negative and neutral emotion conditions for small outcomes (including wins and losses), whereas there was no difference between the three conditions for large outcomes. In addition, the amplitudes of P3 were reduced overall in the negative emotion condition. We suggest that incidental emotions have modulated both the option assessment stage (manifested in behavioral choices) and the outcome evaluation stage (manifested in ERP amplitudes) of decision making unconsciously (indicated by unchanged subjective emotional experiences). The current findings have expanded our understanding of the role of incidental emotion in decision making. PMID- 27354123 TI - Randomized Phase 3 Trials of Accelerated Partial Breast Irradiation: A Trickle Before the Deluge. PMID- 27354124 TI - Editorial Statement on Gleason Scoring for Prostate Cancer. PMID- 27354126 TI - Protons for Oropharyngeal Cancer Have Not Yet Justified Their Promise. PMID- 27354125 TI - Intensity Modulated Proton Therapy Versus Intensity Modulated Photon Radiation Therapy for Oropharyngeal Cancer: First Comparative Results of Patient-Reported Outcomes. AB - PURPOSE: We hypothesized that patients with oropharyngeal cancer treated with intensity modulated proton therapy (IMPT) would have lower symptom burdens, as measured by patient-reported outcome (PRO) surveys, than patients treated with intensity modulated photon therapy (IMRT). METHODS AND MATERIALS: Patients were treated for oropharyngeal cancer from 2006 to 2015 through prospective registries with concurrent chemotherapy and IMPT or chemotherapy and IMRT and completed the MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN) module at various times before treatment (baseline), during treatment (acute phase), within the first 3 months after treatment (subacute phase), and afterward (chronic phase). Individual symptoms and the top 5 and top 11 most severe symptoms were summarized and compared between the radiation therapy modalities. RESULTS: PRO data were collected and analyzed from 35 patients treated with chemotherapy and IMPT and from 46 treated with chemotherapy and IMRT. The baseline symptom burdens were similar between both groups. The overall top 5 symptoms were food taste problems (mean score 4.91 on a 0-10 scale), dry mouth (4.49), swallowing/chewing difficulties (4.26), lack of appetite (4.08), and fatigue (4.00). Among the top 11 symptoms, changes in taste and appetite during the subacute and chronic phases favored IMPT (all P<.048). No differences in symptom burden were detected between modalities during the acute and chronic phases by top-11 symptom scoring. During the subacute phase, the mean (+/-standard deviation) top 5 MDASI scores were 5.15 +/- 2.66 for IMPT versus 6.58 +/- 1.98 for IMRT (P=.013). CONCLUSIONS: According to the MDASI-HN, symptom burden was lower among the IMPT patients than among the IMRT patients during the subacute recovery phase after treatment. A prospective randomized clinical trial is underway to define the value of IMPT for the management of head and neck tumors. PMID- 27354127 TI - Reirradiation of Head and Neck Cancers With Intensity Modulated Radiation Therapy: Outcomes and Analyses. AB - PURPOSE: To review our 15-year institutional experience using intensity modulated radiation therapy (IMRT) to reirradiate patients with head and neck squamous cell carcinomas (HNSCC) and identify predictors of outcomes and toxicity. METHODS AND MATERIALS: We retrospectively reviewed the records of 227 patients who received head and neck reirradiation using IMRT from 1999 to 2014. Patients treated with noncurative intent were excluded. Radiation-related acute and late toxicities were recorded. Prognostic variables included performance status, disease site, disease-free interval, chemotherapy, and RT dose and volume. Correlative analyses were performed separately for surgery and nonsurgery patients. RESULTS: Two hundred six patients (91%) were retreated with curative intent, and 173 had HNSCC histology; 104 (50%) underwent salvage resection, and 135 (66%) received chemotherapy. Median follow-up after reirradiation was 24.7 months. Clinical outcomes were worse for HNSCC patients, with 5-year locoregional control, progression-free survival, and overall survival rates of 53%, 22%, and 32%, respectively, compared with 74%, 59%, and 79%, respectively, for non-HNSCC patients. On multivariate analysis, concurrent chemotherapy and retreatment site were associated with tumor control, whereas performance status was associated with survival. Favorable prognostic factors specific to surgery patients were neck retreatment and lack of extracapsular extension, whereas for nonsurgery patients, these were a nasopharynx subsite and complete response to induction chemotherapy. Actuarial rates of grade >=3 toxicity were 32% at 2 years and 48% at 5 years, with dysphagia or odynophagia being most common. Increased grade >=3 toxicity was associated with retreatment volume >50 cm(3) and concurrent chemotherapy. CONCLUSIONS: Reirradiation with IMRT either definitively or after salvage surgery can produce promising local control and survival in selected patients with head and neck cancers. Treatment-related toxicity remains significant. Prognostic factors are emerging to guide multidisciplinary treatment approaches and clinical trial design. PMID- 27354128 TI - The Short-Term and Intermediate-Term Risk of Second Neoplasms After Diagnosis and Treatment of Unilateral Vestibular Schwannoma: Analysis of 9460 Cases. AB - PURPOSE: To determine the incidence of second intracranial neoplasms after the diagnosis and treatment of sporadic vestibular schwannoma (VS). METHODS AND MATERIALS: Analysis of the Surveillance, Epidemiology, and End Results (SEER) database including all patients identified with a diagnosis of VS and a second intracranial tumor. The Kaplan-Meier method was used to determine the incidence of second tumors while allowing for censoring at loss to follow-up or death. Multivariable associations between treatment modality and second tumor formation were explored using Cox proportional hazards regression analysis. Two illustrative cases are also presented. RESULTS: In all, 9460 patients with unilateral VS were identified between 2004 and 2012. Overall, 66 (0.7%) patients experienced a separate intracranial tumor, benign or malignant, after treatment of VS. Kaplan-Meier estimates for time to second neoplasm at 1, 3, and 5 years were 0.3%, 0.7%, and 0.8%, respectively. Multivariable comparison between VS treatment modalities revealed that the risk of second tumor formation was similar between radiation and surgery (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.36-1.51; P=.93) but greater for tumors managed with observation alone compared with radiation (HR 2.48; 95% CI 1.31-4.71; P<.01). A total of 6 (0.06%) intracranial malignancies were diagnosed after VS treatment. Kaplan-Meier estimates for time to malignancy at 1, 3, and 5 years were 0%, 0.1%, and 0.1%, respectively. After adjustment for age at diagnosis, sex, and treatment modality, the probability of malignancy after radiation was not greater than after observation alone or microsurgery (HR 4.88; 95% CI 0.85-28.14; P=.08) during the study period. CONCLUSIONS: The risk for the development of a second intracranial neoplasm, benign or malignant, at 5 years after treatment of unilateral VS is approximately 0.8%, whereas the risk of acquiring a separate malignancy is 0.1%, or approximately 1 per 1000 cases. The short-term and intermediate-term incidence of second neoplasm after radiation of VS is not greater than the incidence after microsurgery or observation. PMID- 27354130 TI - Requirements and Implementation of a Lung SBRT Program in a Developing Country: Benefits of International Cooperation. PMID- 27354129 TI - N08C9 (Alliance): A Phase 3 Randomized Study of Sulfasalazine Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy. AB - PURPOSE: To provide confirmatory evidence on the use of sulfasalazine to reduce enteritis during pelvic radiation therapy (RT), following 2 prior single institution trials suggestive that benefit existed. METHODS AND MATERIALS: A multi-institution, randomized, double-blind, placebo-controlled phase 3 trial was designed to assess the efficacy of sulfasalazine versus placebo in the treatment of RT-related enteritis during RT including the posterior pelvis (45.0-53.5 Gy) and conducted through a multicenter national cooperative research alliance. Patients received 1000 mg of sulfasalazine or placebo orally twice daily during and for 4 weeks after RT. The primary endpoint was maximum severity of diarrhea (Common Terminology Criteria for Adverse Events version 4.0). Toxicity and bowel function were assessed by providers through a self-administered bowel function questionnaire taken weekly during RT and for 6 weeks afterward. RESULTS: Eighty seven patients were enrolled in the trial between April 29, 2011, and May 13, 2013, with evenly distributed baseline factors. At the time of a planned interim toxicity analysis, more patients with grade >=3 diarrhea received sulfasalazine than received placebo (29% vs 11%, P=.04). A futility analysis showed that trial continuation would be unlikely to yield a positive result, and a research board recommended halting study treatment. Final analysis of the primary endpoint showed no significant difference in maximum diarrhea severity between the sulfasalazine and placebo arms (P=.41). CONCLUSIONS: Sulfasalazine does not reduce enteritis during pelvic RT and may be associated with a higher risk of adverse events than placebo. This trial illustrates the importance of confirmatory phase 3 trials in the evaluation of symptom-control agents. PMID- 27354131 TI - Role of Adjuvant Radiation Therapy After Surgery for Abdominal Desmoplastic Small Round Cell Tumors. AB - PURPOSE: To identify the prognostic role of adjuvant abdominal radiation therapy (RT) on oncologic outcomes as a part of multimodal treatment in the management of desmoplastic small round cell tumor (DSRCT) and to determine its impact according to the quality of surgical resection. METHODS AND MATERIALS: All patients treated for primary abdominal DSRCT in 8 French centers from 1991 to 2014 were included. Patients were retrospectively staged into 3 groups: group A treated with adjuvant RT after cytoreductive surgery, group B without RT after cytoreductive surgery, and group C by exclusive chemotherapy. Peritoneal progression-free survival (PPFS), progression-free survival (PFS), and overall survival (OS) were evaluated. We also performed a direct comparison between groups A and B to evaluate RT after cytoreductive surgery. Radiation therapy was also evaluated according to completeness of surgery: complete cytoreductive surgery (CCS) or incomplete cytoreductive surgery (ICS). RESULTS: Thirty-seven (35.9%), thirty-six (34.9%), and thirty (28.0%) patients were included in groups A, B, and C, respectively. Three-year OS was 61.2% (range, 41.0%-76.0%), 37.6% (22.0%-53.1%), and 17.3% (6.3%-32.8%) for groups A, B, and C, respectively. Overall survival, PPFS, and PFS differed significantly among the 3 groups (P<.001, P<.001, and P<.001, respectively). Overall survival and PPFS were higher in group A (RT group) compared with group B (no RT group) (P=.045 and P=.006, respectively). Three-year PPFS was 23.8% (10.3%-40.4%) for group A and 12.51% (4.0%-26.2%) for group B. After CCS, RT improved PPFS (P=.024), but differences in OS and PFS were not significant (P=.40 and P=.30, respectively). After ICS, RT improved OS (P=.044). A trend of PPFS and PFS increase was observed, but the difference was not statistically significant (P=.073 and P=.076). CONCLUSIONS: Adjuvant RT as part of multimodal treatment seems to confer oncologic benefits for patients treated for abdominal DSRCT after cytoreductive surgery and perioperative chemotherapy. PMID- 27354132 TI - The Promise of the Abscopal Effect and the Future of Trials Combining Immunotherapy and Radiation Therapy. PMID- 27354133 TI - The Pace of Progress in Radiation and Immunotherapy. PMID- 27354135 TI - The American Society for Radiation Oncology's 2015 Core Physics Curriculum for Radiation Oncology Residents. AB - PURPOSE: The American Society for Radiation Oncology (ASTRO) Physics Core Curriculum Subcommittee (PCCSC) has updated the recommended physics curriculum for radiation oncology resident education to improve consistency in teaching, intensity, and subject matter. METHODS AND MATERIALS: The ASTRO PCCSC is composed of physicists and physicians involved in radiation oncology residency education. The PCCSC updated existing sections within the curriculum, created new sections, and attempted to provide additional clinical context to the curricular material through creation of practical clinical experiences. Finally, we reviewed the American Board of Radiology (ABR) blueprint of examination topics for correlation with this curriculum. RESULTS: The new curriculum represents 56 hours of resident physics didactic education, including a 4-hour initial orientation. The committee recommends completion of this curriculum at least twice to assure both timely presentation of material and re-emphasis after clinical experience. In addition, practical clinical physics and treatment planning modules were created as a supplement to the didactic training. Major changes to the curriculum include addition of Fundamental Physics, Stereotactic Radiosurgery/Stereotactic Body Radiation Therapy, and Safety and Incidents sections, and elimination of the Radiopharmaceutical Physics and Dosimetry and Hyperthermia sections. Simulation and Treatment Verification and optional Research and Development in Radiation Oncology sections were also added. A feedback loop was established with the ABR to help assure that the physics component of the ABR radiation oncology initial certification examination remains consistent with this curriculum. CONCLUSIONS: The ASTRO physics core curriculum for radiation oncology residents has been updated in an effort to identify the most important physics topics for preparing residents for careers in radiation oncology, to reflect changes in technology and practice since the publication of previous recommended curricula, and to provide practical training modules in clinical radiation oncology physics and treatment planning. The PCCSC is committed to keeping the curriculum current and consistent with the ABR examination blueprint. PMID- 27354134 TI - Regional Lung Function Profiles of Stage I and III Lung Cancer Patients: An Evaluation for Functional Avoidance Radiation Therapy. AB - PURPOSE: The development of clinical trials is underway to use 4-dimensional computed tomography (4DCT) ventilation imaging to preferentially spare functional lung in patients undergoing radiation therapy. The purpose of this work was to generate data to aide with clinical trial design by retrospectively characterizing dosimetric and functional profiles for patients with different stages of lung cancer. METHODS AND MATERIALS: A total of 118 lung cancer patients (36% stage I and 64% stage III) from 2 institutions were used for the study. A 4DCT-ventilation map was calculated using the patient's 4DCT imaging, deformable image registration, and a density-change-based algorithm. To assess each patient's spatial ventilation profile both quantitative and qualitative metrics were developed, including an observer-based defect observation and metrics based on the ventilation in each lung third. For each patient we used the clinical doses to calculate functionally weighted mean lung doses and metrics that assessed the interplay between the spatial location of the dose and high functioning lung. RESULTS: Both qualitative and quantitative metrics revealed a significant difference in functional profiles between the 2 stage groups (P<.01). We determined that 65% of stage III and 28% of stage I patients had ventilation defects. Average functionally weighted mean lung dose was 19.6 Gy and 5.4 Gy for stage III and I patients, respectively, with both groups containing patients with large spatial overlap between dose and high-function regions. CONCLUSION: Our 118 patient retrospective study found that 65% of stage III patients have regionally variant ventilation profiles that are suitable for functional avoidance. Our results suggest that regardless of disease stage, it is possible to have unique spatial interplay between dose and high-functional lung, highlighting the importance of evaluating the function of each patient and developing a personalized functional avoidance treatment approach. PMID- 27354136 TI - Spatial Precision in Magnetic Resonance Imaging-Guided Radiation Therapy: The Role of Geometric Distortion. AB - Because magnetic resonance imaging-guided radiation therapy (MRIgRT) offers exquisite soft tissue contrast and the ability to image tissues in arbitrary planes, the interest in this technology has increased dramatically in recent years. However, intrinsic geometric distortion stemming from both the system hardware and the magnetic properties of the patient affects MR images and compromises the spatial integrity of MRI-based radiation treatment planning, given that for real-time MRIgRT, precision within 2 mm is desired. In this article, we discuss the causes of geometric distortion, describe some well-known distortion correction algorithms, and review geometric distortion measurements from 12 studies, while taking into account relevant imaging parameters. Eleven of the studies reported phantom measurements quantifying system-dependent geometric distortion, while 2 studies reported simulation data quantifying magnetic susceptibility-induced geometric distortion. Of the 11 studies investigating system-dependent geometric distortion, 5 reported maximum measurements less than 2 mm. The simulation studies demonstrated that magnetic susceptibility-induced distortion is typically smaller than system-dependent distortion but still nonnegligible, with maximum distortion ranging from 2.1 to 2.6 mm at a field strength of 1.5 T. As expected, anatomic landmarks containing interfaces between air and soft tissue had the largest distortions. The evidence indicates that geometric distortion reduces the spatial integrity of MRI-based radiation treatment planning and likely diminishes the efficacy of MRIgRT. Better phantom measurement techniques and more effective distortion correction algorithms are needed to achieve the desired spatial precision. PMID- 27354137 TI - In Regard to Chapman et al. PMID- 27354138 TI - In Regard to Kubicek et al. PMID- 27354139 TI - In Reply to Rovirosa and Herreros. PMID- 27354140 TI - In Reply to Alongi and Fiorentino. PMID- 27354141 TI - In Regard to Pan et al. PMID- 27354142 TI - In Regard to Nagata et al. PMID- 27354143 TI - Substrate-induced structures of bismuth adsorption on graphene: a first principles study. AB - The geometric and electronic properties of Bi-adsorbed monolayer graphene, enriched by the strong effect of a substrate, are investigated by first principles calculations. The six-layered substrate, corrugated buffer layer, and slightly deformed monolayer graphene are all simulated. Adatom arrangements are thoroughly studied by analyzing the ground-state energies, bismuth adsorption energies, and Bi-Bi interaction energies of different adatom heights, inter adatom distance, adsorption sites, and hexagonal positions. A hexagonal array of Bi atoms is dominated by the interactions between the buffer layer and the monolayer graphene. An increase in temperature can overcome a ~50 meV energy barrier and induce triangular and rectangular nanoclusters. The most stable and metastable structures agree with the scanning tunneling microscopy measurements. The density of states exhibits a finite value at the Fermi level, a dip at ~-0.2 eV, and a peak at ~-0.6 eV, as observed in the experimental measurements of the tunneling conductance. PMID- 27354144 TI - Comparative morphology of the hemolymph vascular system in Uropygi and Amblypygi (Arachnida): Complex correspondences support Arachnopulmonata. AB - Although the circulatory system of arthropods has long been considered as rather simple, recent studies have demonstrated that in certain arthropod taxa, such as Malacostraca, some Chilopoda and also many Chelicerata, the vascular systems in particular are rather complex. Furthermore, a recent study has revealed that the prosomal ganglion of scorpions and spiders is supplied by an intricate network of arteries, the complexity of which bears a close resemblance to that of vertebrate capillary systems. In this study, we analyzed the hemolymph vascular systems of various species of Pedipalpi (i.e., Amblypygi and Uropygi). By combining modern techniques, such as MicroCT and cLSM, with computer-based 3D-reconstruction, we were able to produce comprehensive visualizations and descriptions of the vascular systems. Despite the lack of well-corroborated phylogenetic hypotheses on arachnid relationships and the controversial assertion of relationships between the pulmonate arachnids, we aim to elucidate the evolution of complex vascular systems in Arachnida. By comparing these highly complex vascular systems not only with each other, but also with other pulmonate arachnids, we found numerous detailed correspondences in the general branching pattern as well as in the supply patterns of the prosomal ganglion. We argue that these numerous and detailed correspondences by their absence in other arachnids i.e. aplumonates, support Arachnopulmonata. J. Morphol. 277:1084-1103, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27354146 TI - The alveolar-arterial oxygen difference in acute pulmonary thromboembolism: a classical concept revisited. PMID- 27354147 TI - The effect of captopril on the expression of MMP-9 and the prognosis of neurological function in herpes simplex encephalitis mice. AB - BACKGROUND AND PURPOSE: Early increased matrix metalloproteinase-9 (MMP-9) expression is involved in the evolution of herpes simplex encephalitis (HSE) by facilitating the development of cerebrovascular complications. However, the molecular mechanism underlying the detrimental effects of MMP-9 in HSE has not been elucidated. Recent research finds angiotensin II plays an important role in regulation of MMP-9 activity. The aim of this work was to identify the influence of angiotensin-converting enzyme inhibitor (ACEI) captopril on MMP-9 activation after herpes simplex virus 1 (HSV-1) infection. METHODS: Animal models of HSE were established by intracerebral inoculation of HSV-1 into mice. Brain tissue ROS levels were measured by staining with dihydroethidium. MMP-9 protein expression was detected by immunofluorescence and brain water content was measured with dry-wet weight method. Neurological function score was quantified 5 d after HSV-1 infection. Microglial cells were treated with various concentrations of captopril. MMP-9 gelatinolytic activity in the supematant of the cell cultures was assessed by zymography. RT-PCR was used to detect the mRNA expressions of p47phox and MMP-9. RESULTS: Immunofluorescence showed that expression of MMP-9 in brain tissue was mainly presented in OX-42 positive microglia. Quantification of gelatinolytic activity by densitometry showed that expression of MMP-9 in microglia was significantly increased after HSV-1 infection and inhibited by captopril treatment. NADPH oxidase subunit p47phox and MMP-9 mRNA expression were significantly increased 6 h after HSV-1 infection, and were seen reduced after captopril treatment in dose dependence. Captopril also downregulated ROS and MMP-9 protein expression following encephalitis in vivo, and attenuated brain edema, and improved neurological function. DISCUSSION: This compelling evidence suggests that MMP-9 is a key pathogenic factor within HSE. ACEI captopril could reduce the expression of MMP-9 mediated by ROS, then relieve cerebral edema and improve neurological function, which may lay a foundation for further basic research and clinical application. PMID- 27354148 TI - MicroRNA-223 affects IL-6 secretion in mast cells via the IGF1R/PI3K signaling pathway. AB - In this study, we aimed to assess the effects of microRNA-223 (miR-223) on interleukin-6 (IL-6) secretion in mast cells and determine the underlying molecular mechanisms. Mast cells (P815) were transfected with miR-223 lentiviral vector and miR-223 inhibitor. miR-223 expression was then evaluated using reverse transcription-quantitative PCR (RT-qPCR). IL-6 levels in the supernatant were analyzed using enzyme-linked immunosorbent assay. The signaling pathways in mast cells with downregulated miR-223 were initially evaluated by gene chip. Downregulation of miR-223 and its target gene was tested using a luciferase reporter assay. The expression of phosphate-AKT (p-AKT) and its target protein insulin-like growth factor-1 receptor (IGF1R) was assessed by western blot analysis. Phosphatidylinositol 3-kinase (PI3K)-inhibitor (LY294002) and insulin like growth factor-1 (IGF1) were used to determine the effect of miR-223 on IL-6 secretion in mast cells. The results showed that microRNA-223 reduced IL-6 concentration in the mast cells. The gene chip results predicted an induction of the PI3K-AKT signaling pathway in the mast cells. Luciferase reporter assay confirmed IGF1R gene to be a target of miR-223. The p-AKT and IGF1R levels increased following miR-223 downregulation in mast cells. In addition, the specific PI3K-inhibitor LY294002 decreased IL-6 secretion. Incubation with IGF1 resulted in the induction of IL-6 secretion in miR-223-expressing mast cells. In conclusion, it was shown that miR-223 reduces IL-6 secretion in mast cells by inhibiting the IGF1R/PI3K signaling pathway. PMID- 27354149 TI - The evolution of comprehensive haemophilia care in the United States: perspectives from the frontline. AB - The establishment of dedicated comprehensive treatment centres more than a half century ago transformed the management of haemophilia in the United States. Formerly, a disease associated with crippling disability and premature death, today, persons with haemophilia who are treated appropriately from infancy and do not develop inhibitors can expect a normal life expectancy and relatively few bleeding episodes. The evolution of the comprehensive haemophilia care, while chastened by the viral epidemics of the 1980s, has been marked by ongoing advances, including prophylaxis, immune tolerance induction, new drugs and gene therapy research. Current challenges include sustaining the comprehensive care model despite decreased funding and expanding the delivery and affordability of comprehensive haemophilia care. PMID- 27354150 TI - In vivo delineation of subdivisions of the human amygdaloid complex in a high resolution group template. AB - The nuclei of the human amygdala remain difficult to distinguish in individual subject structural magnetic resonance images. However, interpretation of the amygdala's role in whole brain networks requires accurate localization of functional activity to a particular nucleus or subgroup of nuclei. To address this, high spatial resolution, three-dimensional templates, using joint high accuracy diffeomorphic registration of T1- and T2-weighted structural images from 168 typical adults between 22 and 35 years old released by the Human Connectome Project were constructed. Several internuclear boundaries are clearly visible in these templates, which would otherwise be impossible to delineate in individual subject data. A probabilistic atlas of major nuclei and nuclear groups was constructed in this template space and mapped back to individual spaces by inversion of the individual diffeomorphisms. Group level analyses revealed a slight (~2%) bias toward larger total amygdala and nuclear volumes in the right hemisphere. No substantial sex or age differences were found in amygdala volumes normalized to total intracranial volume, or subdivision volumes normalized to amygdala volume. The current delineation provides a finer parcellation of the amygdala with more accurate external boundary definition than current histology based atlases when used in conjunction with high accuracy registration methods, such as diffeomorphic warping. These templates and delineation are intended to be an open and evolving resource for future functional and structural imaging studies of the human amygdala. Hum Brain Mapp 37:3979-3998, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27354151 TI - Imaging Techniques in Percutaneous Cardiac Structural Interventions: Atrial Septal Defect Closure and Left Atrial Appendage Occlusion. AB - Because of advances in cardiac structural interventional procedures, imaging techniques are playing an increasingly important role. Imaging studies show sufficient anatomic detail of the heart structure to achieve an excellent outcome in interventional procedures. Up to 98% of atrial septal defects at the ostium secundum can be closed successfully with a percutaneous procedure. Candidates for this type of procedure can be identified through a systematic assessment of atrial septum anatomy, locating and measuring the size and shape of all defects, their rims, and the degree and direction of shunting. Three dimensional echocardiography has significantly improved anatomic assessments and the end result itself. In the future, when combined with other imaging techniques such as cardiac computed tomography and fluoroscopy, 3-dimensional echocardiography will be particularly useful for procedure guidance. Percutaneous closure of the left atrial appendage offers an alternative for treating patients with atrial fibrillation and contraindication for oral anticoagulants. In the future, the clinical focus may well turn to stroke prevention in selected patients. Percutaneous closure is effective and safe; device implantation is successful in 94% to 99% of procedures. However, the procedure requires an experienced cardiac structural interventional team. At present, 3-dimensional echocardiography is the most appropriate imaging technique to assess anatomy suitability, select device type and size, guide the procedure alongside fluoroscopy, and to follow-up the patient afterwards. PMID- 27354152 TI - Percutaneous Closure of Fistula Secondary to Infective Endocarditis. PMID- 27354153 TI - D-dimer levels and recurrence in patients with unprovoked VTE and a negative qualitative D-dimer test after treatment. AB - BACKGROUND: The rate of recurrent venous thromboembolism (VTE) in patients with a first unprovoked VTE who had a negative qualitative D-dimer test one month after stopping anticoagulant therapy was higher than expected in the D-dimer Optimal Duration Study (DODS). OBJECTIVES: To determine whether quantitative D-dimer levels using a low threshold, age- and sex-specific thresholds, or repeated measurements, would improve identification of patients at low risk of recurrent VTE. MATERIALS AND METHODS: D-dimer levels were quantified in banked samples from 307 patients in DODS who had a negative qualitative D-dimer test while on, and 1month after stopping, anticoagulant therapy and the rates of recurrent VTE were determined in patients with D-dimer levels below various predefined thresholds. RESULTS: The rate (per patient year) of recurrent VTE was: 5.9% with D-dimer levels<250MUg/l at one month; 5.2% with D-dimer levels between 250 and 499MUg/l at one month; 5.0% with D-dimer levels less than predefined age- and sex-specific thresholds at one month; and 6.3% when D-dimer levels were <500MUg/l at both one and 7months after stopping anticoagulant therapy. These rates are similar to the overall event rate of 6.3% in patients who stopped treatment. CONCLUSIONS: Among unprovoked VTE patients who had a negative qualitative D-dimer test during and after anticoagulant therapy, low D-dimer thresholds, age and sex-adjusted thresholds or repeated measurements, did not identify subgroups with a very low rate of recurrence. PMID- 27354154 TI - Cost-of-illness model for venous thromboembolism. PMID- 27354155 TI - Informational laws of genome structures. AB - In recent years, the analysis of genomes by means of strings of length k occurring in the genomes, called k-mers, has provided important insights into the basic mechanisms and design principles of genome structures. In the present study, we focus on the proper choice of the value of k for applying information theoretic concepts that express intrinsic aspects of genomes. The value k = lg2(n), where n is the genome length, is determined to be the best choice in the definition of some genomic informational indexes that are studied and computed for seventy genomes. These indexes, which are based on information entropies and on suitable comparisons with random genomes, suggest five informational laws, to which all of the considered genomes obey. Moreover, an informational genome complexity measure is proposed, which is a generalized logistic map that balances entropic and anti-entropic components of genomes and is related to their evolutionary dynamics. Finally, applications to computational synthetic biology are briefly outlined. PMID- 27354156 TI - Active tumor-targeting luminescent gold clusters with efficient urinary excretion. AB - We present novel active targeting luminescent gold nanoclusters (AuNCs), which are prepared through a one-pot procedure by using a pentapeptide (CRGDS) for stabilization and tumor recognition. CRGDS-AuNCs exhibit a high tumor-specific retention with an exceptionally high tumor-to-liver uptake ratio of 9.3. Their small hydrodynamic diameter and zwitterionic surface facilitate urinary excretion, which reaches 82% within 24 h after injection. PMID- 27354157 TI - [Latex allergy in a paediatric hospital. Characteristics and risk factors]. AB - INTRODUCTION: The prevalence of latex sensitisation varies according to the population studied. There are various risk factors that increase latex sensitisation, such as genetic risk, atopy, and multiple surgeries. OBJECTIVE: To characterise patients referred to an Immunology Unit with suspected latex allergy, and to analyse their clinical features and risk factors. PATIENTS AND METHOD: A retrospective, descriptive study was conducted on children suspected of latex allergy. Their medical records were reviewed in order to assess symptoms with contact or exposure to latex materials. Known risk factors to latex sensitisation, such as pathologies requiring repeated surgery (spina bifida, myelomeningocele, scoliosis and nephro-urological alterations), atopy (rhinitis, asthma, atopic dermatitis) were investigated. A prick test and/or specific IgE to latex were also performed. A multivariate logistic regression model was performed to find associations between symptoms triggered by exposure to latex with underlying diseases and other risk conditions. RESULTS: A total of 106 patients were enrolled in the study, of whom 50 were evaluable. At diagnosis 96% of patients were older than five years. Most of the risk factors described were observable in these patients, such as multiple surgeries, neurological and nephro urological malformations, surgery before one year-old, and repeated bladder catheterisation. After latex exposure, mucous cutaneous manifestations were the most common (52%), followed by respiratory symptoms (36%). All patients were sensitised and allergic to latex. CONCLUSION: Latex allergy is a significant problem in children with risk factors. The results shown in this study raise important challenges for preventive measures and awareness. PMID- 27354159 TI - Scaled particle focusing in a microfluidic device with asymmetric electrodes utilizing induced-charge electroosmosis. AB - We propose a novel continuous-flow microfluidic particle concentrator with a specified focusing-particle number ratio (FR) at different channel outlets using induced-charge electroosmosis (ICEO). The particle-focusing region contains two floating electrodes of asymmetric widths L2 and L1 in the gap between a driving electrode pair, all of which are fabricated in parallel in the main channel. Applying an AC voltage over the driving electrodes, an ICEO flow with two vortexes can be induced over each of the two floating electrodes, and the actuation range of the ICEO vortex is proportional to the respective electrode size. We establish a preliminary physical model for the value of FR: at a moderate voltage and frequency range, FR approaches L2/L1 due to the scaled ICEO actuation range; by further modifying the voltage or frequency, FR is freely adjustable because of the variation in ICEO velocity. Furthermore, by connecting multiple focusing regions in series, i.e., high FR = (L2/L1)(n) can be conveniently generated in an n-stage flow focusing device. Our results provide a promising method for yielding transverse concentration gradients of particles useful in pre-processing before analysis. PMID- 27354158 TI - Mesenchymal stem cells alleviate experimental rheumatoid arthritis through microRNA-regulated IkappaB expression. AB - Previous studies have demonstrated that mesenchymal stem cell (MSC) transplantation reduces the severity of collagen-induced arthritis (CIA) in mice, which is a model for rheumatoid arthritis (RA) in humans. However, the underlying molecular mechanisms remain ill-defined. Here, we showed that MSC transplantation reduced the activities of NF-kappaB signaling and decreased microRNA-548e (miR 548e) levels in the joint tissue in CIA-mice, seemingly through activation of transforming growth factor beta receptor signaling. Bioinformatics analyses revealed that miR-548e inhibited protein translation of the NF-kappaB inhibitor, IkappaB, through binding to the 3'-UTR of the IkappaB mRNA. MSCs co-transplanted with adeno-associated virus (AAV) carrying miR-548e abolished the therapeutic effects of MSCs on CIA. On the other hand, transplantation of AAV carrying antisense of miR-548e (as-miR-548e) partially mimicked the effects of MSC transplantation on CIA. Together, these data suggest that MSC transplantation may alleviate experimental RA partially through suppressing miR-548e-mediated IkappaB inhibition. PMID- 27354160 TI - BioNSi: A Discrete Biological Network Simulator Tool. AB - Modeling and simulation of biological networks is an effective and widely used research methodology. The Biological Network Simulator (BioNSi) is a tool for modeling biological networks and simulating their discrete-time dynamics, implemented as a Cytoscape App. BioNSi includes a visual representation of the network that enables researchers to construct, set the parameters, and observe network behavior under various conditions. To construct a network instance in BioNSi, only partial, qualitative biological data suffices. The tool is aimed for use by experimental biologists and requires no prior computational or mathematical expertise. BioNSi is freely available at http://bionsi.wix.com/bionsi , where a complete user guide and a step-by-step manual can also be found. PMID- 27354161 TI - Predisposition or side effect of the duration: the reactivity of the HPA-axis under psychosocial stress in panic disorder. AB - BACKGROUND: Panic disorder (PD) has been associated with an altered reactivity of the hypothalamic-pituitary-adrenocortical (HPA) system under psychosocial stress. Until now it remains unclear whether a diminished cortisol release is an early risk factor predisposing for PD or a consequence of PD. In order to unravel this point, the present study compares the cortisol secretion between patients with a recent onset and a chronic course of PD. METHODS: The Trier Social Stress Test (TSST) was applied in patients with a duration of PD <= 1.5 years (N = 35), patients with a duration of PD > 1.5 years (N = 56) and healthy controls (N = 95). Salivary cortisol and heart rate (HR) were assessed as primary outcomes. RESULTS: According to baseline cortisol/baseline HR and HR response there was no significant difference. Both patient groups (<= 1.5/> 1.5 years) showed a blunted cortisol response with no significant group difference. In multiple linear regression models the attenuation of the HPA-axis was largely accounted for by group, smoking status, use of contraceptive pill and the interaction group by gender. Female patients with a chronic course showed the lowest cortisol response under the TSST. CONCLUSIONS: It might be assumed that a decreased reactivity of the HPA-axis could be considered as etiological risk factor in the preliminary stages of PD. Above, female gender, smoking status and the use of contraceptive pill seem to further moderate the attenuated HPA-axis response pattern in patients with PD. PMID- 27354162 TI - Superconcentrated electrolytes for a high-voltage lithium-ion battery. AB - Finding a viable electrolyte for next-generation 5 V-class lithium-ion batteries is of primary importance. A long-standing obstacle has been metal-ion dissolution at high voltages. The LiPF6 salt in conventional electrolytes is chemically unstable, which accelerates transition metal dissolution of the electrode material, yet beneficially suppresses oxidative dissolution of the aluminium current collector; replacing LiPF6 with more stable lithium salts may diminish transition metal dissolution but unfortunately encounters severe aluminium oxidation. Here we report an electrolyte design that can solve this dilemma. By mixing a stable lithium salt LiN(SO2F)2 with dimethyl carbonate solvent at extremely high concentrations, we obtain an unusual liquid showing a three dimensional network of anions and solvent molecules that coordinate strongly to Li(+) ions. This simple formulation of superconcentrated LiN(SO2F)2/dimethyl carbonate electrolyte inhibits the dissolution of both aluminium and transition metal at around 5 V, and realizes a high-voltage LiNi0.5Mn1.5O4/graphite battery that exhibits excellent cycling durability, high rate capability and enhanced safety. PMID- 27354163 TI - Dipole and quadrupole polarizabilities of the water molecule as a function of geometry. AB - Dipolar, dipole-quadrupole and quadrupole-quadrupole static polarizabilities of the water molecule have been determined by ab initio calculations at coupled cluster level of theory with single, double and perturbative triple excitations CCSD(T) with an aug-cc-pVTZ basis set using a finite field and field-gradient method. The geometry dependence of polarizability tensor components has been explored and modeled by power series expansion in bond length and angle variations up to sum of powers equal to 4. The results provide a very detailed description of the static polarizability of water up to quadrupolar rank which can be used for the test and development of novel accurate polarizable interaction potentials for modeling aqueous solutions. (c) 2016 Wiley Periodicals, Inc. PMID- 27354164 TI - Therapeutic Vaccination against A Modified Minimal Survivin Epitope Induces Functional CD4 T Cells That Recognize Survivin-Expressing Cells. PMID- 27354165 TI - Discovery and identification of candidate genes from the chitinase gene family for Verticillium dahliae resistance in cotton. AB - Verticillium dahliae, a destructive and soil-borne fungal pathogen, causes massive losses in cotton yields. However, the resistance mechanism to V. dahilae in cotton is still poorly understood. Accumulating evidence indicates that chitinases are crucial hydrolytic enzymes, which attack fungal pathogens by catalyzing the fungal cell wall degradation. As a large gene family, to date, the chitinase genes (Chis) have not been systematically analyzed and effectively utilized in cotton. Here, we identified 47, 49, 92, and 116 Chis from four sequenced cotton species, diploid Gossypium raimondii (D5), G. arboreum (A2), tetraploid G. hirsutum acc. TM-1 (AD1), and G. barbadense acc. 3-79 (AD2), respectively. The orthologous genes were not one-to-one correspondence in the diploid and tetraploid cotton species, implying changes in the number of Chis in different cotton species during the evolution of Gossypium. Phylogenetic classification indicated that these Chis could be classified into six groups, with distinguishable structural characteristics. The expression patterns of Chis indicated their various expressions in different organs and tissues, and in the V. dahliae response. Silencing of Chi23, Chi32, or Chi47 in cotton significantly impaired the resistance to V. dahliae, suggesting these genes might act as positive regulators in disease resistance to V. dahliae. PMID- 27354166 TI - Neurophysiology versus clinical genetics in Rett syndrome: A multicenter study. AB - Many studies have attempted to establish the genotype-phenotype correlation in Rett syndrome (RTT). Cardiorespiratory measurements provide robust objective data, to correlate with each of the different clinical phenotypes. It has important implications for the management and treatment of this syndrome. The aim of this study was to correlate the genotype with the quantitative cardiorespiratory data obtained by neurophysiological measurement combined with a clinical severity score. This international multicenter study was conducted in four European countries from 1999 to 2012. The study cohort consisted of a group of 132 well-defined RTT females aged between 2 and 43 years with extended clinical, molecular, and neurophysiological assessments. Diagnosis of RTT was based on the consensus criteria for RTT and molecular confirmation. Genotype phenotype analyses of clinical features and cardiorespiratory data were performed after grouping mutations by the same type and localization or having the same putative biological effect on the MeCP2 protein, and subsequently on eight single recurrent mutations. A less severe phenotype was seen in females with CTS, p.R133C, and p.R294X mutations. Autonomic disturbances were present in all females, and not restricted to nor influenced by one specific group or any single recurrent mutation. The objective information from non-invasive neurophysiological evaluation of the disturbed central autonomic control is of great importance in helping to organize the lifelong care for females with RTT. Further research is needed to provide insights into the pathogenesis of autonomic dysfunction, and to develop evidence-based management in RTT. (c) 2016 Wiley Periodicals, Inc. PMID- 27354167 TI - Working 9-5: Causal Relationships Between Singers' "Day Jobs" and Their Performance Work, With Implications for Vocal Health. AB - OBJECTIVES: It is acknowledged generally that professional contemporary commercial music (CCM) singers engage in supplementary employment ("the day job") to achieve and maintain a reliable living wage. In this paper, consideration is given to the impact of such nonperformance employment on CCM's sustainable vocal health. METHODS: Collected data from a survey of 102 professional contemporary gig singers were analysed using descriptive statistical procedures from the Statistical Package for the Social Sciences. Although these data provided descriptions of the personal characteristics of individuals in the sample, the inclusion of open format questions encouraged participants to report details of their "lived" experience. Additionally, a meta-analysis of a range of associated literature was undertaken. RESULTS: Sixty-five participants (N = 102) reported that in addition to their heavy performance voice use, they were employed in "other" work (the "day job") where their speaking voice loads were high. In responding to open-ended questions, many proffered written comments that were unprompted. The collected data from this element of the research study are reported here. CONCLUSIONS: We propose that at least some causal factors of singers' reported voice problems may lie in the misuse or overuse of their everyday speaking voice (as demanded by their "day job") rather than a misuse of their singing voice. These findings have practical application to all whose concern is care for the vocal or emotional health and performance longevity of professional singers. PMID- 27354168 TI - Food for thought: do you ask about eating? PMID- 27354169 TI - Mind the gap - surviving in the modern world. PMID- 27354170 TI - Diabetes and collision risk. A meta-analysis and meta-regression. AB - AIMS: The main objective of this study was to see whether diabetes is associated with an increased collision risk and to test the effect of age and gender on the overall collision risk for diabetes drivers. MATERIALS AND METHODS: Twenty-eight studies were included in meta-analysis, using mean age, gender, continent and the prevalence of fatal road incidents as covariates. RESULTS: The collision risk for diabetes drivers was small and not statistically significant - RR = 1.11 (1.01 1.23) with a prediction interval (PI) or 0.77-1.65. Age and gender were not associated with an increased overall risk. Insulin-dependent diabetes patients had a slightly increased effect size compared with the overall diabetes population, but the effect was not statistically significant. European diabetes drivers had a lower collision risk compared with their North American counterparts, the main cause being the difference of collision risk in the countries in which the studies were performed. CONCLUSIONS: Overall, diabetes patients do not have a statistically significant increased risk for unfavourable traffic events. Old age and insulin-dependent patients tend to have a higher risk. Advances in diabetes care, associated with advances in road safety regulations, and automotive industry have not decreased significantly the collision risk in the last 50 years for drivers with diabetes. PMID- 27354171 TI - The spectre of ghostwriting: eroding public trust in physicians, clinical trial integrity and biomedical authorship. AB - The impact of medical ghostwriting, a violation of authorship ethics, remains unclear within the biomedical literature and among the public, potentially raising concerns about the integrity of the biomedical evidence base. Core texts in authorship and ghostwriting from the clinical literature and the 2010 Senate Minority Report on ghostwriting were reviewed as were uses of the term 'ghostwriting' in contemporary (2009-2011) and more recent (2015-2016) journalistic news coverage originally printed in English. Journalistic coverage oversimplified key concerns about ghostwriting identified by the medical community and the US government. More recent journalistic uses of the term 'ghostwriting' suggest confusion with topics such as financial disclosures or patient monitoring. Pharmaism in the medical literature, an expression of bias against pharmaceutical companies that casts doubt on the credibility of physicians and scientists, may be a source for confusion. The tendency for medical journal editors to discuss ghostwriting in the context of clinical trial transparency or data integrity is another possible source for misinterpretation via oversimplification. Journalistic descriptions of ghostwriting consistently downplay the critical reasoning abilities and competence of practising physicians and deflect attention away from patient concerns and back to pharmaceutical companies. Some uses of the term ghostwriting in news coverage may implicitly undercut belief in the competence of physicians, a troubling trend. Further work is needed to characterise the impact of ghostwriting in the medical literature and to reassure the public that their trust in medical practitioners is well placed. PMID- 27354172 TI - Analysis of transposable elements and organellar DNA in male and female genomes of a species with a huge Y chromosome reveals distinct Y centromeres. AB - Few angiosperms have distinct Y chromosomes. Among those that do are Silene latifolia (Caryophyllaceae), Rumex acetosa (Polygonaceae) and Coccinia grandis (Cucurbitaceae), the latter having a male/female difference of 10% of the total genome (female individuals have a 0.85 pg genome, male individuals 0.94 pg), due to a Y chromosome that arose about 3 million years ago. We compared the sequence composition of male and female C. grandis plants and determined the chromosomal distribution of repetitive and organellar DNA with probes developed from 21 types of repetitive DNA, including 16 mobile elements. The size of the Y chromosome is largely due to the accumulation of certain repeats, such as members of the Ty1/copia and Ty3/gypsy superfamilies, an unclassified element and a satellite, but also plastome- and chondriome-derived sequences. An abundant tandem repeat with a unit size of 144 bp stains the centromeres of the X chromosome and the autosomes, but is absent from the Y centromere. Immunostaining with pericentromere-specific markers for anti-histone H3Ser10ph and H2AThr120ph revealed a Y-specific extension of these histone marks. That the Y centromere has a different make-up from all the remaining centromeres raises questions about its spindle attachment, and suggests that centromeric or pericentromeric chromatin might be involved in the suppression of recombination. PMID- 27354173 TI - Targeted drug delivery to emphysematous lungs: Inhibition of MMPs by doxycycline loaded nanoparticles. PMID- 27354174 TI - [Plasma homocysteine, Lp(a), and oxidative stress markers in peripheral macroangiopathy in patients with type 2 diabetes mellitus]. AB - AIM: To study new risk factors for peripheral macroangiopathy (PM) in patients with diabetes, as oxidative stress (OS) and its interaction with classical risk factors: age, Lp(a), plasma homocysteine values and HbA1c. SUBJECTS AND METHODS: We studied 204 type2 diabetic (T2DM) patients, consecutive selected form a reference hospital and a secondary hospital form our Community (2009-2010). Design was a case (ABI<0.89) control (ABI0.9-1.2) study. PM was defined using ankle brachial index (ABI). Thirty nine T2DM subjects presented ABI>1.2 and were excluded. Clinical and biological parameters were determined using standard methods. RESULTS: Comparing clinical and biological parameters obtained in both studied groups (T2DM+ABI<0.9 vs T2DM+ABI0.9-1.2), we found statistical significant differences in age, evolution time of diabetes, Lp(a) and plasma homocysteine values. No differences were found in OS parameters: reduced glutathione, oxidized glutathione and maloldialdehide between studied groups. Plasma homocysteine values were an independent risk factor for the presence of PM and were related to evolution time of diabetes and reduced glutathione. CONCLUSIONS: We have confirmed that Lp(a) and independently plasma homocysteine values were related to PM in T2DM subjects. No association with PM and OS markers (GSH, GSSG and MDA) were found in T2DM with more than 10years of evolution time of their disease and high prevalence of chronic complications. PMID- 27354175 TI - The calcium-activated potassium channel KCa3.1 is an important modulator of hepatic injury. AB - The calcium-activated potassium channel KCa3.1 controls different cellular processes such as proliferation and volume homeostasis. We investigated the role of KCa3.1 in experimental and human liver fibrosis. KCa3.1 gene expression was investigated in healthy and injured human and rodent liver. Effect of genetic depletion and pharmacological inhibition of KCa3.1 was evaluated in mice during carbon tetrachloride induced hepatic fibrogenesis. Transcription, protein expression and localisation of KCa3.1 was analysed by reverse transcription polymerase chain reaction, Western blot and immunohistochemistry. Hemodynamic effects of KCa3.1 inhibition were investigated in bile duct-ligated and carbon tetrachloride intoxicated rats. In vitro experiments were performed in rat hepatic stellate cells and hepatocytes. KCa3.1 expression was increased in rodent and human liver fibrosis and was predominantly observed in the hepatocytes. Inhibition of KCa3.1 aggravated liver fibrosis during carbon tetrachloride challenge but did not change hemodynamic parameters in portal hypertensive rats. In vitro, KCa3.1 inhibition leads to increased hepatocyte apoptosis and DNA damage, whereas proliferation of hepatic stellate cells was stimulated by KCa3.1 inhibition. Our data identifies KCa3.1 channels as important modulators in hepatocellular homeostasis. In contrast to previous studies in vitro and other tissues this channel appears to be anti-fibrotic and protective during liver injury. PMID- 27354176 TI - Development and evaluation of an ultrasonic personal aerosol sampler. AB - Assessing personal exposure to air pollution has long proven challenging due to technological limitations posed by the samplers themselves. Historically, wearable aerosol monitors have proven to be expensive, noisy, and burdensome. The objective of this work was to develop a new type of wearable monitor, an ultrasonic personal aerosol sampler (UPAS), to overcome many of the technological limitations in personal exposure assessment. The UPAS is a time-integrated monitor that features a novel micropump that is virtually silent during operation. A suite of onboard environmental sensors integrated with this pump measure and record mass airflow (0.5-3.0 L/min, accurate within 5%), temperature, pressure, relative humidity, light intensity, and acceleration. Rapid development of the UPAS was made possible through recent advances in low-cost electronics, open-source programming platforms, and additive manufacturing for rapid prototyping. Interchangeable cyclone inlets provided a close match to the EPA PM2.5 mass criterion (within 5%) for device flows at either 1.0 or 2.0 L/min. Battery life varied from 23 to 45 hours depending on sample flow rate and selected filter media. Laboratory tests of the UPAS prototype demonstrate excellent agreement with equivalent federal reference method samplers for gravimetric analysis of PM2.5 across a broad range of concentrations. PMID- 27354177 TI - Development and validation of the NDDI-E-Y: a screening tool for depressive symptoms in pediatric epilepsy. AB - OBJECTIVES: To validate the revised 12-item revised Neurological Disorders Depression Inventory-Epilepsy for Youth (NDDI-E-Y), a self-report screening tool for depressive symptoms tailored to youth ages 12-17 with epilepsy. METHODS: Youth at two sites completed the NDDI-E-Y during a routine epilepsy visit. Youth at one site also completed the Children's Depression Inventory-2 (CDI-2). Seizure and demographic data were abstracted from the electronic medical record. Exploratory factor analyses were conducted. Internal consistency, area under the curve (AUC), and construct validity were assessed. RESULTS: NDDI-E-Y questionnaires were analyzed for 143 youth. The coefficient for internal consistency for the NDDI-E-Y was 0.92. Factor analyses suggested a one-factor solution with all 12 items loading on the factor. The NDDI-E-Y was positively correlated with the CDI-2 (N = 99). Sensitivity and specificity of the NDDI-E-Y were high. SIGNIFICANCE: Reliability and construct validity were established for the revised 12-item NDDI-E-Y. The NDDI-E-Y is a brief, free measure of depressive symptoms that can be administered during a routine epilepsy visit. PMID- 27354178 TI - Subsurface Super-resolution Imaging of Unstained Polymer Nanostructures. AB - Optical imaging has offered unique advantages in material researches, such as spectroscopy and lifetime measurements of deeply embedded materials, which cannot be matched using electron or scanning-probe microscopy. Unfortunately, conventional optical imaging cannot provide the spatial resolutions necessary for many nanoscopic studies. Despite recent rapid progress, super-resolution optical imaging has yet to be widely applied to non-biological materials. Herein we describe a method for nanoscopic optical imaging of buried polymer nanostructures without the need for extrinsic staining. We observed intrinsic stochastic fluorescence emission or blinking from unstained polymers and performed spatial temporal spectral analysis to investigate its origin. We further applied photon localization super-resolution imaging reconstruction to the detected stochastic blinking, and achieved a spatial resolution of at least 100 nm, which corresponds to a six-fold increase over the optical diffraction limit. This work demonstrates the potential for studying the static heterogeneities of intrinsic polymer molecular-specific properties at sub-diffraction-limited optical resolutions. PMID- 27354179 TI - Albinism, stigma, subjectivity and global-local discourses in Tanzania. AB - Societal ideas and explanations of albinism at the local level in Tanzania are conceived in terms of family history, social relations, economic status, moral religious positions, global-local flows of information and humanitarian actions on behalf of people with the congenital condition. This paper aims to show how the subjectivities of people with albinism in Tanzania are shaped and re-shaped through local moral conceptions as well as globalizing (bio)medical explanations of albinism. An exemplary case study of a 28-year-old woman, plus episodes from the lives of seven other informants with the condition, are analyzed in order to understand, on the one hand, local social relationships between people with albinism and other individuals in family and community settings, and on the other hand, the interconnections between persons with albinism and global humanitarian actors and the broadcast media. When stigma and marginalizing behaviors are perceived by individuals with albinism in Tanzania as impeding their social lives, they employ different coping strategies and discourses to enhance social acceptance. PMID- 27354180 TI - A new phylogeny and environmental DNA insight into paramyxids: an increasingly important but enigmatic clade of protistan parasites of marine invertebrates. AB - Paramyxida is an order of rhizarian protists that parasitise marine molluscs, annelids and crustaceans. They include notifiable pathogens (Marteilia spp.) of bivalves and other taxa of economic significance for shellfish production. The diversity of paramyxids is poorly known, particularly outside of commercially important hosts, and their phylogenetic position is unclear due to their extremely divergent 18S rDNA sequences. However, novel paramyxean lineages are increasingly being detected in a wide range of invertebrate hosts, and interest in the group is growing, marked by the first 'Paramyxean Working Group' Meeting held in Spain in February 2015. We review the diversity, host affiliations, and geographical ranges of all known paramyxids, present a comprehensive phylogeny of the order and clarify its taxonomy. Our phylogenetic analyses confirm the separate status of four genera: Paramarteilia, Marteilioides, Paramyxa and Marteilia. Further, as including M. granula in Marteilia would make the genus paraphyletic we suggest transferring this species to a new genus, Eomarteilia. We present sequence data for Paramyxa nephtys comb. n., a parasite of polychaete worms, providing morphological data for a clade of otherwise environmental sequences, sister to Marteilioides. Light and electron microscopy analyses show strong similarities with both Paramyxa and Paramyxoides, and we further discuss the validity of those two genera. We provide histological and electron microscopic data for Paramarteilia orchestiae, the type species of that genus originally described from the amphipod Orchestia; in situ hybridisation shows that Paramarteilia also infects crab species. We present, to our knowledge, the first known results of a paramyxid-specific environmental DNA survey of environmental (filtered water, sediment, etc.) and organismally-derived samples, revealing new lineages and showing that paramyxids are associated with a wider range of hosts and habitat types than previously known. On the basis of our new phylogeny we propose phylogenetic hypotheses for evolution of lifecycle and infectivity traits observed in different paramyxid genera. PMID- 27354181 TI - HIV therapy with unknown HBV status is responsible for higher rate of HBV genome variability in Ethiopia. AB - BACKGROUND: In Ethiopia, HBV and HIV are co-circulating. Since patients are not routinely tested for HBV, the use of antiretroviral drugs could contribute to unintended HBV drug resistance and surface gene variability during HIV coinfection. METHODS: A total of 161 hepatitis B surface antigen (HBsAg)-positive sera from 58 HIV-coinfected and 103 drug-naive HBV-monoinfected individuals were characterized for HBV drug resistance and immune escape HBsAg variants. HBV polymerase/surface gene fragment of 716 bp was analysed by direct sequencing. RESULTS: In 34 out of 161 study subjects (21.1%) HBV drug resistance mutations (DRMs) were detected with a frequency of 3.1% rtL80F/I, 0.6% rtA181V, 1.2% rtT184S, 6.2% rtV173L, 10.6% rtL180M, 10.6% rtM204V/I and 8.1% rtI233V. The prevalence of the major DRMs in HBV-HIV-coinfected individuals was significantly higher than monoinfected individuals (41.4% versus 10.7%). Lamivudine selected DRMs, that is, rtL180M (29.3%) and rtM204V/I (29.3%) and rtV173L (15.5%) were more prevalent in HBV-HIV-coinfected individuals but absent in HBV-monoinfected individuals. Despite the finding that rtL180M and rtM204V/I were higher among ART experienced individuals, the overall prevalence of DRMs (48.0% versus 36.4%) showed no significance difference among antiretroviral therapy (ART) status. The study also revealed higher frequency and heterogeneity of putative and known immune escape HBsAg mutations both in the major hydrophilic region (MHR; 68.3%) and outside the MHR (82.5%) of the surface gene. In particular, the 'a' determinant surface gene mutations (sT125S, sA128V, sQ129H/R, sT131I, sC137S, sT143M, sD144D/E, sG145R, sT148P) and the majority of clustered/multiple as well as drug selected immune escape HBsAg mutations were more prevalent in HBV-HIV coinfected individuals. CONCLUSIONS: HIV therapy without HBV co-management in Ethiopia fosters emergence and circulation of HBV variants of public health importance. It is highly recommended to include HBV testing and co-management as part of routine HIV care programmes for a better ART selection. PMID- 27354182 TI - No-Prep Rehabilitation of Fractured Maxillary Incisors with Partial Veneers. AB - OBJECTIVE: Therapeutic options for dental trauma depend on the injuries' features. For patients with uncomplicated tooth fractures, adhesive materials and composite partial veneers may be a therapeutic solution that completely preserves healthy tooth structure. CLINICAL CONSIDERATIONS: An ultra-conservative approach, using indirect composite partial veneers to restore fractured anterior teeth is described in these case reports. CONCLUSION: Despite the position of the finish line in the middle of the clinical crown, this solution offers functional and esthetic outcomes using an indirect composite technique, and appears to be a suitable alternative to direct composite restorations or less conservative indirect veneers. CLINICAL SIGNIFICANCE: Indirect composite partial veneers present considerable advantages, such as ultra-minimally invasive properties and excellent esthetic appearances. The success seems to depend on a combination of sound adhesive principles, adequate design of the restoration, laboratory experience, and cementation techniques. (J Esthet Restor Dent 28:351-358, 2016). PMID- 27354183 TI - A preliminary insight of correlation between human fecal microbial diversity and blood lipid profile. AB - The study aimed to evaluate the effect of human gut-derived lactic acid bacteria and yeast on cholesterol levels. Fecal samples from five healthy volunteers were examined for the level and diversity of dominant microbiota. Pichia kudriavzevii (QAUPK01, QAUPK02, QAUPK03, QAUPK04 and QAUPK05) and Candida tropicalis (QAUCT06) were identified by phenotypic methods and DNA sequencing and tested for in vitro cholesterol assimilation ability. Significant correlations (p < 0.05) between fecal microbial diversity, volunteers' age, body mass index (BMI) and serum lipid profile were established. From biochemical tests, eight strains of lactic acid bacteria (M1.1, M1.2, M2.1, M3.1, M3.2, M4.1, M5.1 and M5.2) were identified but no bsh activity was found in them. However, all yeast strains were able to assimilate cholesterol and maximum assimilation ability was shown by QAUPK03 (83.6%) and QAUPK05 (85.2%) after 72 h of growth at 37 degrees C. PMID- 27354184 TI - Observation of number-density-dependent growth of plasmonic nanobubbles. AB - Interaction dynamics of laser pulses and nanoparticles are of great interest in recent years. In many cases, laser-nanoparticle interactions result in the formation of plasmonic nanobubbles, and the dynamics of nanoparticles and nanobubbles are inseparable. So far, very little attention has been paid to the number density. Here we report the first observation of number-density-dependent growth of plasmonic nanobubbles. Our results show that the nanobubbles growth depends (does not depend) on the number density at high (low) laser fluence, although the inter-particle distance in the solution is as long as 14-30 MUm. This cannot be explained by the existing physical picture, and we propose a new model which takes into account the pressure waves arising from nanoparticles. The numerical results based on this model agree well with the experimental results. Our findings imply that the number density can be a new doorknob to control laser nanobubble as well as laser-nanoparticle interactions. PMID- 27354185 TI - Evaluating random search strategies in three mammals from distinct feeding guilds. AB - Searching allows animals to find food, mates, shelter and other resources essential for survival and reproduction and is thus among the most important activities performed by animals. Theory predicts that animals will use random search strategies in highly variable and unpredictable environments. Two prominent models have been suggested for animals searching in sparse and heterogeneous environments: (i) the Levy walk and (ii) the composite correlated random walk (CCRW) and its associated area-restricted search behaviour. Until recently, it was difficult to differentiate between the movement patterns of these two strategies. Using a new method that assesses whether movement patterns are consistent with these two strategies and two other common random search strategies, we investigated the movement behaviour of three species inhabiting sparse northern environments: woodland caribou (Rangifer tarandus caribou), barren-ground grizzly bear (Ursus arctos) and polar bear (Ursus maritimus). These three species vary widely in their diets and thus allow us to contrast the movement patterns of animals from different feeding guilds. Our results showed that although more traditional methods would have found evidence for the Levy walk for some individuals, a comparison of the Levy walk to CCRWs showed stronger support for the latter. While a CCRW was the best model for most individuals, there was a range of support for its absolute fit. A CCRW was sufficient to explain the movement of nearly half of herbivorous caribou and a quarter of omnivorous grizzly bears, but was insufficient to explain the movement of all carnivorous polar bears. Strong evidence for CCRW movement patterns suggests that many individuals may use a multiphasic movement strategy rather than one behaviour strategies such as the Levy walk. The fact that the best model was insufficient to describe the movement paths of many individuals suggests that some animals living in sparse environments may use strategies that are more complicated than those described by the standard random search models. Thus, our results indicate a need to develop movement models that incorporate factors such as the perceptual and cognitive capacities of animals. PMID- 27354186 TI - Update on the Risk of Introduction of African Swine Fever by Wild Boar into Disease-Free European Union Countries. AB - Despite efforts to prevent the appearance and spread of African swine fever (ASF) in the European Union, several Member States are now affected (Lithuania, Poland, Latvia and Estonia). Disease appearance in 2014 was associated with multiple entrances linked to wild boar movement from endemic areas (EFSA Journal, 8, 2015, 1556), but the risk of new introductions remains high (Gallardo et al., Porcine Health Management, 1, and 21) as ASF continues to be active in endemic countries (Russian Federation, Belarus and Ukraine). Since 2014, the number of ASF notifications has increased substantially, particularly in wild boar (WB), in parallel with slow but constant geographical advance of the disease. This situation suggests a real risk of further disease spread into other Member States, posing a great threat to pig production in the EU. Following the principles of the risk-based veterinary surveillance, this article applies a methodology developed by De la Torre et al. (Transboundary and Emerging Diseases, 62, and 272) to assess the relative risk of new introductions of ASF by natural movements of WB according to the current epidemiological situation. This update incorporates the most recent available data and an improved version of the most important risk estimator: an optimized cartographic tool of WB distribution to analyse wild boar suitable habitat. The highest relative risk values were estimated for Slovakia (5) and Romania (5), followed by Finland (4), Czech Republic (3) and Germany (3). Relative risk for Romania and Finland is associated mainly with disease entrance from endemic areas such as the Russian Federation and Ukraine, where the disease is currently spreading; relative risk for Germany and Czech Republic is associated mainly with the potential progress of the disease through the EU, and relative risk for Slovakia is associated with both pathways. WB habitat is the most important risk estimator, whereas WB density is the least significant, suggesting that WB presence is more relevant than density. These results can provide actionable advice for dealing with risk. They can be directly used to inform risk-based national strategies and identify countries that may need to pay greater attention to surveillance or conduct additional evaluations at the subnational level. PMID- 27354188 TI - Towards Artificial Speech Therapy: A Neural System for Impaired Speech Segmentation. AB - This paper presents a neural system-based technique for segmenting short impaired speech utterances into silent, unvoiced, and voiced sections. Moreover, the proposed technique identifies those points of the (voiced) speech where the spectrum becomes steady. The resulting technique thus aims at detecting that limited section of the speech which contains the information about the potential impairment of the speech. This section is of interest to the speech therapist as it corresponds to the possibly incorrect movements of speech organs (lower lip and tongue with respect to the vocal tract). Two segmentation models to detect and identify the various sections of the disordered (impaired) speech signals have been developed and compared. The first makes use of a combination of four artificial neural networks. The second is based on a support vector machine (SVM). The SVM has been trained by means of an ad hoc nested algorithm whose outer layer is a metaheuristic while the inner layer is a convex optimization algorithm. Several metaheuristics have been tested and compared leading to the conclusion that some variants of the compact differential evolution (CDE) algorithm appears to be well-suited to address this problem. Numerical results show that the SVM model with a radial basis function is capable of effective detection of the portion of speech that is of interest to a therapist. The best performance has been achieved when the system is trained by the nested algorithm whose outer layer is hybrid-population-based/CDE. A population-based approach displays the best performance for the isolation of silence/noise sections, and the detection of unvoiced sections. On the other hand, a compact approach appears to be clearly well-suited to detect the beginning of the steady state of the voiced signal. Both the proposed segmentation models display outperformed two modern segmentation techniques based on Gaussian mixture model and deep learning. PMID- 27354187 TI - Automatic Tuning of a Retina Model for a Cortical Visual Neuroprosthesis Using a Multi-Objective Optimization Genetic Algorithm. AB - The retina is a very complex neural structure, which contains many different types of neurons interconnected with great precision, enabling sophisticated conditioning and coding of the visual information before it is passed via the optic nerve to higher visual centers. The encoding of visual information is one of the basic questions in visual and computational neuroscience and is also of seminal importance in the field of visual prostheses. In this framework, it is essential to have artificial retina systems to be able to function in a way as similar as possible to the biological retinas. This paper proposes an automatic evolutionary multi-objective strategy based on the NSGA-II algorithm for tuning retina models. Four metrics were adopted for guiding the algorithm in the search of those parameters that best approximate a synthetic retinal model output with real electrophysiological recordings. Results show that this procedure exhibits a high flexibility when different trade-offs has to be considered during the design of customized neuro prostheses. PMID- 27354189 TI - A Structural Parametrization of the Brain Using Hidden Markov Models-Based Paths in Alzheimer's Disease. AB - The usage of biomedical imaging in the diagnosis of dementia is increasingly widespread. A number of works explore the possibilities of computational techniques and algorithms in what is called computed aided diagnosis. Our work presents an automatic parametrization of the brain structure by means of a path generation algorithm based on hidden Markov models (HMMs). The path is traced using information of intensity and spatial orientation in each node, adapting to the structure of the brain. Each path is itself a useful way to characterize the distribution of the tissue inside the magnetic resonance imaging (MRI) image by, for example, extracting the intensity levels at each node or generating statistical information of the tissue distribution. Additionally, a further processing consisting of a modification of the grey level co-occurrence matrix (GLCM) can be used to characterize the textural changes that occur throughout the path, yielding more meaningful values that could be associated to Alzheimer's disease (AD), as well as providing a significant feature reduction. This methodology achieves moderate performance, up to 80.3% of accuracy using a single path in differential diagnosis involving Alzheimer-affected subjects versus controls belonging to the Alzheimer's disease neuroimaging initiative (ADNI). PMID- 27354190 TI - Reconstruction of Neural Activity from EEG Data Using Dynamic Spatiotemporal Constraints. AB - We present a novel iterative regularized algorithm (IRA) for neural activity reconstruction that explicitly includes spatiotemporal constraints, performing a trade-off between space and time resolutions. For improving the spatial accuracy provided by electroencephalography (EEG) signals, we explore a basis set that describes the smooth, localized areas of potentially active brain regions. In turn, we enhance the time resolution by adding the Markovian assumption for brain activity estimation at each time period. Moreover, to deal with applications that have either distributed or localized neural activity, the spatiotemporal constraints are expressed through [Formula: see text] and [Formula: see text] norms, respectively. For the purpose of validation, we estimate the neural reconstruction performance in time and space separately. Experimental testing is carried out on artificial data, simulating stationary and non-stationary EEG signals. Also, validation is accomplished on two real-world databases, one holding Evoked Potentials and another with EEG data of focal epilepsy. Moreover, responses of functional magnetic resonance imaging for the former EEG data have been measured in advance, allowing to contrast our findings. Obtained results show that the [Formula: see text]-based IRA produces a spatial resolution that is comparable to the one achieved by some widely used sparse-based estimators of brain activity. At the same time, the [Formula: see text]-based IRA outperforms other similar smooth solutions, providing a spatial resolution that is lower than the sparse [Formula: see text]-based solution. As a result, the proposed IRA is a promising method for improving the accuracy of brain activity reconstruction. PMID- 27354191 TI - EEG-Based Detection of Starting and Stopping During Gait Cycle. AB - Walking is for humans an essential task in our daily life. However, there is a huge (and growing) number of people who have this ability diminished or are not able to walk due to motor disabilities. In this paper, a system to detect the start and the stop of the gait through electroencephalographic signals has been developed. The system has been designed in order to be applied in the future to control a lower limb exoskeleton to help stroke or spinal cord injured patients during the gait. The brain-machine interface (BMI) training has been optimized through a preliminary analysis using the brain information recorded during the experiments performed by three healthy subjects. Afterward, the system has been verified by other four healthy subjects and three patients in a real-time test. In both preliminary optimization analysis and real-time tests, the results obtained are very similar. The true positive rates are [Formula: see text] and [Formula: see text] respectively. Regarding the false positive per minute, the values are also very similar, decreasing from 2.66 in preliminary tests to 1.90 in real-time. Finally, the average latencies in the detection of the movement intentions are 794 and 798[Formula: see text]ms, preliminary and real-time tests respectively. PMID- 27354192 TI - A Computational Framework for Realistic Retina Modeling. AB - Computational simulations of the retina have led to valuable insights about the biophysics of its neuronal activity and processing principles. A great number of retina models have been proposed to reproduce the behavioral diversity of the different visual processing pathways. While many of these models share common computational stages, previous efforts have been more focused on fitting specific retina functions rather than generalizing them beyond a particular model. Here, we define a set of computational retinal microcircuits that can be used as basic building blocks for the modeling of different retina mechanisms. To validate the hypothesis that similar processing structures may be repeatedly found in different retina functions, we implemented a series of retina models simply by combining these computational retinal microcircuits. Accuracy of the retina models for capturing neural behavior was assessed by fitting published electrophysiological recordings that characterize some of the best-known phenomena observed in the retina: adaptation to the mean light intensity and temporal contrast, and differential motion sensitivity. The retinal microcircuits are part of a new software platform for efficient computational retina modeling from single-cell to large-scale levels. It includes an interface with spiking neural networks that allows simulation of the spiking response of ganglion cells and integration with models of higher visual areas. PMID- 27354193 TI - A Fly-Inspired Mushroom Bodies Model for Sensory-Motor Control Through Sequence and Subsequence Learning. AB - Classification and sequence learning are relevant capabilities used by living beings to extract complex information from the environment for behavioral control. The insect world is full of examples where the presentation time of specific stimuli shapes the behavioral response. On the basis of previously developed neural models, inspired by Drosophila melanogaster, a new architecture for classification and sequence learning is here presented under the perspective of the Neural Reuse theory. Classification of relevant input stimuli is performed through resonant neurons, activated by the complex dynamics generated in a lattice of recurrent spiking neurons modeling the insect Mushroom Bodies neuropile. The network devoted to context formation is able to reconstruct the learned sequence and also to trace the subsequences present in the provided input. A sensitivity analysis to parameter variation and noise is reported. Experiments on a roving robot are reported to show the capabilities of the architecture used as a neural controller. PMID- 27354194 TI - Generalized Models for the Classification of Abnormal Movements in Daily Life and its Applicability to Epilepsy Convulsion Recognition. AB - The identification and the modeling of epilepsy convulsions during everyday life using wearable devices would enhance patient anamnesis and monitoring. The psychology of the epilepsy patient penalizes the use of user-driven modeling, which means that the probability of identifying convulsions is driven through generalized models. Focusing on clonic convulsions, this pre-clinical study proposes a method for generating a type of model that can evaluate the generalization capabilities. A realistic experimentation with healthy participants is performed, each with a single 3D accelerometer placed on the most affected wrist. Unlike similar studies reported in the literature, this proposal makes use of [Formula: see text] cross-validation scheme, in order to evaluate the generalization capabilities of the models. Event-based error measurements are proposed instead of classification-error measurements, to evaluate the generalization capabilities of the model, and Fuzzy Systems are proposed as the generalization modeling technique. Using this method, the experimentation compares the most common solutions in the literature, such as Support Vector Machines, [Formula: see text]-Nearest Neighbors, Decision Trees and Fuzzy Systems. The event-based error measurement system records the results, penalizing those models that raise false alarms. The results showed the good generalization capabilities of Fuzzy Systems. PMID- 27354195 TI - Announcement: The 2016 Hojjat Adeli Award for Outstanding Contributions in Neural Systems. PMID- 27354196 TI - Maternal Concern for Child Undereating. AB - OBJECTIVE: To describe features of maternal concern for her child undereating; examine maternal and child correlates of maternal concern for undereating; and determine whether maternal concern for undereating is associated with feeding practices. METHODS: This was a cross-sectional analysis of an observational study with 286 mother-child dyads (mean child age, 71 months). Maternal concern for undereating was assessed using a semistructured interview. Mothers completed questionnaires to assess picky eating, food neophobia, and feeding practices. Feeding practices were further assessed using videotaped mealtime observations. Logistic regression was used to assess the association of maternal and child characteristics with maternal concern for undereating. Regression was used to assess the association of maternal concern for undereating with feeding practices, controlling for covariates. RESULTS: Over a third of mothers (36.5%) expressed concern that their child does not eat enough. Correlates of concern for undereating included child body mass index z-score (BMIz; odds ratio [OR] = 0.58; 95% confidence interval [CI], 0.43-0.77) and picky eating (OR = 2.41; 95% CI, 1.26-4.59). Maternal concern for undereating was associated with greater reported pressure to eat (relative risk [RR] = 1.97; 95% CI, 1.55-2.50), greater observed bribery (OR = 2.63; 95% CI, 1.50-4.60), and higher observed pressure (OR = 1.90; 95% CI, 1.08-3.36) during mealtimes. CONCLUSIONS: Mothers of children who are picky eaters and have a lower BMIz are more likely to be concerned that their children do not eat enough, and maternal concern for undereating is associated with pressuring and bribing children to eat. Pediatricians might address maternal concern for undereating by advising feeding practices that do not involve pressure and bribery, particularly among healthy weight children. PMID- 27354197 TI - Universal Cholesterol Screening in Childhood: A Systematic Review. AB - BACKGROUND: In 2011, a US expert panel recommended universal cholesterol screening for children ages 9 to 11 years. Controversy exists over this recommendation, especially because the most recent systematic review on universal childhood screening was inconclusive. OBJECTIVES: To conduct an updated systematic review on universal cholesterol screening in childhood and effect on health outcomes, clinical management, screening acceptability, and healthcare costs. DATA SOURCES: We searched MedLine, EMBASE, Psychinfo, and the Cochrane Registry of Controlled Trials from October 2005 to January 2016. We added new studies identified to those from the previous systematic review (1966-September 2005). STUDY ELIGIBILITY, PARTICIPANTS, AND INTERVENTIONS: We included controlled trials, pre-post, cohort, survey, and qualitative studies of universal cholesterol screening in children ages 0 to 18 years. STUDY APPRAISAL AND SYNTHESIS METHODS: Two independent reviewers assessed abstracts and full-text studies, extracted data, and ranked quality. Cost data were inflation-adjusted to 2015 dollars. RESULTS: Nine new studies met inclusion criteria, taking the total number of relevant studies to 21. Screening was associated with no change in cholesterol in 1 of 1 study on health outcomes. A positive screen for dyslipidemia was associated with diet and/or exercise changes in 29% to 92% of families in 4 of 4 studies. Adherence with new guidelines for universal screening was low (16%-18%) in 3 of 3 studies. Costs per case of familial hypercholesterolemia detected were $12,500 to $20,300. LIMITATIONS: Included studies were heterogeneous in outcomes. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Universal cholesterol screening might have small, positive effects on lifestyle change, but the effect on health remains understudied. PMID- 27354198 TI - Expression and localization of the Xenopus laevis small heat shock protein, HSPB6 (HSP20), in A6 kidney epithelial cells. AB - Small heat shock proteins (sHSPs) are molecular chaperones that bind to unfolded protein, inhibit the formation of toxic aggregates and facilitate their refolding and/or degradation. Previously, the only sHSPs that have been studied in detail in the model frog system, Xenopus laevis, were members of the HSP30 family and HSPB1 (HSP27). We now report the analysis of X. laevis HSPB6, an ortholog of mammalian HSPB6. X. laevis HSPB6 cDNA encodes a 168 aa protein that contains an alpha-crystallin domain, a polar C-terminal extension and some possible phosphorylation sites. X. laevis HSPB6 shares 94% identity with a X. tropicalis HSPB6, 65% with turtle, 59% with humans, 49% with zebrafish and only 50% and 43% with X. laevis HSPB1 and HSP30C, respectively. Phylogenetic analysis revealed that X. laevis HSPB6 grouped more closely with mammalian and reptilian HSPB6s than with fish HSPB6. X. laevis recombinant HSPB6 displayed molecular chaperone properties since it had the ability to inhibit heat-induced aggregation of citrate synthase. Immunoblot analysis determined that HSPB6 was present constitutively in kidney epithelial cells and that heat shock treatment did not upregulate HSPB6 levels. While treatment with the proteasomal inhibitor, MG132, resulted in a 2-fold increase in HSPB6 levels, exposure to cadmium chloride produced a slight increase in HSPB6. These findings were in contrast to HSP70, which was enhanced in response to all three stressors. Finally, immunocytochemical analysis revealed that HSPB6 was present in the cytoplasm in the perinuclear region with some in the nucleus. PMID- 27354199 TI - Rectovaginal fistula: Twenty years of rectovaginal repair. AB - AIM: To identify the favorable factors in rectovaginal fistula (RVF) management. METHODS: After Institutional Review Board approval (99-0793B), we retrospectively studied all patients diagnosed, treated and followed up with RVF at Chang Gung Memorial Hospital, Taiwan between January 1990 and December 2009. All female patients with International Classification of Diseases RVF were included. We reviewed demographic data, socioeconomic status, clinical presentation, comorbidities, method of treatment, duration of hospitalization and clinical outcome at 12 months postoperatively. RESULTS: A total of 397 patients were included in the study. Fifty-six patients (14.1%) had conservative treatment and 341 patients (85.9%) underwent surgical intervention. A total of 125 patients underwent simple repair while 216 patients underwent reconstruction. Three hundred and forty-four patients (86.7%) had improved outcome at 12-month follow up. Age (P = 0.003), education level (P = 0.033), ability to pay insurance (P < 0.001), and choice of treatment (P < 0.0001) were identified as significant favorable factors. An etiological factor associated with favorable outcome was RVF from obstetric complication, while that resulting from malignancy had a less favorable outcome. CONCLUSIONS: Age, education level and ability to pay insurance significantly affect 12-month outcome of RVF. Surgery is the preferred option, while medical treatment should be used only for small rectovaginal fistulas or for patients not suitable for surgery and anesthesia. More support and assistance should be offered to those patients with unfavorable factors, such as old age, low education level and inability to afford insurance. All RVF secondary to obstetrical injury had a 100% favorable outcome compared with those secondary to surgery or malignancy. Women with suspected RVF should receive prompt and extensive evaluation to ensure immediate effective management and prevention of further serious complications. PMID- 27354200 TI - The 13C-Glucose Breath Test for Insulin Resistance Assessment in Adolescents: Comparison with Fasting and Post-Glucose Stimulus Surrogate Markers of Insulin Resistance. AB - OBJECTIVE: To evaluate the use of the 13C-glucose breath test (13C-GBT) for insulin resistance (IR) detection in adolescents through comparison with fasting and post-glucose stimulus surrogates. METHODS: One hundred thirty-three adolescents aged between 10 and 16 years received an oral glucose load of 1.75 g per kg of body weight dissolved in 150 mL of water followed by an oral dose of 1.5 mg/kg of U-13C-Glucose, without a specific maximum dose. Blood samples were drawn at baseline and 120 minutes, while breath samples were obtained at baseline and at 30, 60, 90, 120, 150, and 180 minutes. The 13C-GBT was compared to homeostasis model assessment (HOMA) IR (>=p95 adjusted by gender and age), fasting plasma insulin (>=p90 adjusted by gender and Tanner stage), results of 2 h oral glucose tolerance test (OGTT), insulin levels (>=65 MUU/mL) in order to determine the optimal cut-off point for IR diagnosis. RESULTS: 13C-GBT data, expressed as adjusted cumulative percentage of oxidized dose (A% OD), correlated inversely with fasting and post-load IR surrogates. Sexual development alters A% OD results, therefore individuals were stratified into pubescent and post pubescent. The optimal cut-off point for the 13C-GBT in pubescent individuals was 16.3% (sensitivity=82.8% & specificity=60.6%) and 13.0% in post-pubescents (sensitivity=87.5% & specificity=63.6%), when compared to fasting plasma insulin. Similar results were observed against HOMA and 2-h OGTT insulin. CONCLUSION: The 13C-GBT is a practical and non-invasive method to screen for IR in adolescents with reasonable sensitivity and specificity. PMID- 27354201 TI - Function analysis of Mef2c promoter in muscle differentiation. AB - Regeneration of adult skeletal muscle following injury occurs through the activation of satellite cells that proliferates, differentiates, and fuses with injured myofibers. Myocyte enhancer factor 2 (MEF2) proteins are reported to have the potential contributions to adult muscle regeneration. To further understand Mef2c gene, the promoter of pig Mef2c gene was analyzed in this paper. Quantitative real-time PCR (qRT-PCR) revealed the expression pattern of Mef2c gene in muscle of eight tissues. The Mef2c promoter had the higher transcriptional activity in differentiated C2C12 cells than that in proliferating C2C12 cells, which was accompanied by the upregulation of mRNA expression of Mef2c gene. Function deletion and mutation analyses showed that MyoD and MEF2 binding sites within the Mef2c promoter were responsible for the regulation of Mef2c transcription. MEF2C could upregulate the transcriptional activities of Mef2c promoter constructs, which contained a 3'-end nucleotide sequence with p300 binding site. The electrophoretic mobility shift assays and chromatin immunoprecipitation assays determined the MyoD binding site in Mef2c promoter. These results advanced our knowledge of the promoter of the pig Mef2c gene, and the study of Mef2c promoter regulator elements helped to elucidate the regulation mechanisms of Mef2c in muscle differentiation or muscle repair and regeneration. PMID- 27354202 TI - Conditioning of amitriptyline-induced REM sleep suppression in healthy participants: A randomized controlled trial. AB - Clinical trials in sleep disorders report substantial improvement in symptoms in their placebo groups. Behavioral conditioning is one of the underlying mechanisms of the placebo response. However, we do not know whether, and if so, the extent to which sleep architecture is influenced by behavioral conditioning, similarly to other physiological responses (i.e., those in the immune system). We therefore applied a conditioning paradigm to 39 healthy adults pairing a novel-tasting drink (conditioned stimulus, CS) with the REM sleep suppressing tricyclic antidepressant amitriptyline as unconditioned stimulus during the acquisition phase. Subsequent sole presentation of the CS (together with a placebo pill) in an evocation night led to significantly more REM sleep in the amitriptyline group. Instead of the expected REM sleep suppression in the evocation night, we observed more REM sleep, indicating a rebound that interferes with the conditioned response. PMID- 27354203 TI - Researchers' Intuitions About Power in Psychological Research. AB - Many psychology studies are statistically underpowered. In part, this may be because many researchers rely on intuition, rules of thumb, and prior practice (along with practical considerations) to determine the number of subjects to test. In Study 1, we surveyed 291 published research psychologists and found large discrepancies between their reports of their preferred amount of power and the actual power of their studies (calculated from their reported typical cell size, typical effect size, and acceptable alpha). Furthermore, in Study 2, 89% of the 214 respondents overestimated the power of specific research designs with a small expected effect size, and 95% underestimated the sample size needed to obtain .80 power for detecting a small effect. Neither researchers' experience nor their knowledge predicted the bias in their self-reported power intuitions. Because many respondents reported that they based their sample sizes on rules of thumb or common practice in the field, we recommend that researchers conduct and report formal power analyses for their studies. PMID- 27354204 TI - H3PAgI: generation by laser-ablation and characterization by rotational spectroscopy and ab initio calculations. AB - The new compound H3PAgI has been synthesized in the gas phase by means of the reaction of laser-ablated silver metal with a pulse of gas consisting of a dilute mixture of ICF3 and PH3 in argon. Ground-state rotational spectra were detected and assigned for the two isotopologues H3P(107)AgI and H3P(109)AgI in their natural abundance by means of a chirped-pulse, Fourier-transform, microwave spectrometer. Both isotopologues exhibit rotational spectra of the symmetric-top type, analysis of which led to accurate values of the rotational constant B0, the quartic centrifugal distortion constants DJ and DJK, and the iodine nuclear quadrupole coupling constant chiaa(I) = eQqaa. Ab initio calculations at the explicitly-correlated level of theory CCSD(T)(F12*)/aug-cc-pVDZ confirmed that the atoms PAg-I lie on the C3 axis in that order. The experimental rotational constants were interpreted to give the bond lengths r0(PAg) = 2.3488(20) A and r0(Ag-I) = 2.5483(1) A, in good agreement with the equilibrium lengths of 2.3387 A and 2.5537 A, respectively, obtained in the ab initio calculations. Measures of the strength of the interaction of PH3 and AgI (the dissociation energy De for the process H3PAgI = H3P + AgI and the intermolecular stretching force constant FPAg) are presented and are interpreted to show that the order of binding strength is H3PHI < H3PICl < H3PAgI for these metal-bonded molecules and their halogen-bonded and hydrogen-bonded analogues. PMID- 27354205 TI - Malnutrition coupled with diarrheal and respiratory infections among children in Asia: A systematic review. AB - OBJECTIVE: The purpose of this systematic literature review was to assess the relationship between malnutrition and respiratory and diarrheal infections among children aged five and under living in Asian countries. DESIGN AND SAMPLE: The design was adapted from the PRISMA method to include case-control, cross sectional, ecological, and experimental studies. A review of electronic databases identified 144 articles of which 20 met the inclusion criteria. The inclusion criteria were studies of malnourished children under the age of five with respiratory and/or diarrheal infections, admitted to hospitals or residing in villages throughout countries in Asia, and published between 2005 and 2015. MEASURES: Infection was defined as the presence of a respiratory or diarrheal illness. Malnutrition was predominantly measured by WHO standards. RESULTS: Malnutrition is associated with respiratory and diarrheal infections. Children have higher rates of mortality when both malnourished and experiencing a respiratory infection. CONCLUSION: Further research needs to examine the synergetic effect of diarrheal and respiratory infections in malnourished children and rates of mortality. Public health nurses (PHNs) play a critical role in the prevention and treatment of malnutrition and infections in community and national systems. Obtaining better data will allow PHNs to provide critical care in the most underserved areas throughout Asia. PMID- 27354206 TI - First sporadic case of pathogenic Escherichia coli infection in Black swan in China. AB - A strain of bacteria was isolated from the diseased black swan (Cygnus atratus) died from enteritis diarrhea, and designated tentatively as B-1 strain. Morphological and biochemical tests, as well as phylogenetic analysis derived from 16S rRNA and fimC gene sequencing both strongly indicated that B-1 strain is identical to Escherichia coli. Furthermore, the polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) profile of the isolate was different from that of two reference strains. Antibiotic sensitivity testing of B-1 strain was carried out by the standard Kirby-Bauer disc diffusion method. Animal experiments demonstrated that B-1 strain is pathogenic to mice and chickens. This is first sporadic case of pathogenic E. coli infection in Black swan in China. PMID- 27354207 TI - Effect of Punica granatum on the virulence factors of cariogenic bacteria Streptococcus mutans. AB - Dental caries is caused by acids produced by biofilm-forming Streptococcus mutans from fermentable carbohydrates and bacterial byproducts. Control of these bacteria is important in the prevention of dental caries. This study investigated the effect of the fruit peel of Punica granatum on biofilm formation, acid and extracellular polysaccharides production (EPS) by S. mutans. Pomegranate fruit peels crude extracts were prepared. The Minimum bactericidal concentrations (MBC) were determined against S. mutans. At 3 sub-bactericidal concentrations, the effect on the acid production, biofilm formation and EPS production was determined. The results were analysed using Kruskal-Wallis and Wilcoxon Rank Sum Tests. The lowest MBC was 6.25 mg/mL. Punica granatum significantly inhibited acid production (p < 0.01). After 6 and 24 h, it significantly reduced biofilm formation by 91% and 65% respectively (p < 0.01). The plant extract did not inhibit the production of soluble EPS in either the biofilm or the planktonic growth. However, it significantly reduced the insoluble EPS in the biofilm and the plantktonic (p = < 0.01) form of S. mutans. The crude extract of P. granatum killed cariogenic S. mutans at high concentrations. At sub-bactericidal concentrations, it reduced biofilm formation, acid and EPS production. This suggests that P. granatum extract has the potential to prevent dental caries. PMID- 27354208 TI - The curli biogenesis genes expression level is unassociated with Enterobacter cloacae hsp60 clusters and PFGE genotypes. AB - The objective of this study was to determine the correlation between Enterobacter cloacae complex subspecies and clusters involved in UTI infections and specific pulsotypes, and to assess the contribution of major curli biogenesis genes (csgD, csgA) expression level to pathogenesis of clusters and genotypes. Based on the PFGE analysis, 37 different profiles were observed among which 8 profiles were common types. Real time PCR of csgD and csgA genes of 50 E. cloacae complex in relation to PFGE and hsp60 genotypes showed that all the genetic clusters are not equally involved in pathogenesis of urinary tract infections. It was elucidated in this study that isolates with common PFGE genotypes belonged to identical hsp60 clusters, and the foremost clusters (VI, III, and V) mainly comprised within PFGE common types. In our study, no significant correlation was detected between the specific hsp60 clusters or PFGE genotypes and the expression level of csgD and csgA genes (P-value > 0.05). This is the first study describing that unequivalent contribution of E. cloacae genotypes and clusters in pathogenesis of UTI, is not owing to varied curli biogenesis expression potential. The PFGE genotyping showed more discriminatory power than hsp60 genotyping for epidemiological studies and source tracking purpose. PMID- 27354209 TI - Molecular identification of multi drug resistant bacteria from urinary tract infected urine samples. AB - Urinary tract infections (UTIs) are of great concern in both developing and developed countries all over the world. Even though the infections are more common in women and children, they are at a considerable rate in men and of all ages. The uropathogens causing the infections are spread through various routes. The treatment generally recommended by the physicians is antibiotic usage. But, most of the uropathogens have evolved antibiotic resistance mechanisms. This makes the present situation hectic in control and prevention of UTIs. The present study aims to illustrate the multidrug resistance patterns among isolated bacterial strains from infected urine samples in Odisha state, India. Four bacterial strains were isolated and identified as Proteus sp. SK3, Pseudomonas sp. ADMK77, Proteus sp. BLKB2 and Enterobacter hormaechei strain CW-3 by 16S rRNA gene sequencing. Phylogenetc analysis indicated the strains belong to three various genera namely, Proteus, Pseudomonas and Enterobacter. The evolutionary timeline of the bacteria was studied by constructing phylogenetic trees by Neighborhood Joining method. The presence of ESBL gene and biofilm forming capability were studied for the four strains. Antibiotic susceptibility patterns of the isolates were studied toward the commonly recommended antibiotics. Both the Proteus strains were found commonly susceptible to aminoglycoside and sulphonamide groups. Pseudomonas strain was found to be susceptible to cephems, aminoglycosides and fluoroquinolones. Enterobacter sp was found to be resistant to almost all antibiotic groups and susceptible to only sulphonamides group. The antibiotic susceptibility patterns of the bacteria help in choosing the empirical antibiotic treatment for UTI. PMID- 27354210 TI - gamma-Aminobutyric Acid Is Synthesized and Released by the Endothelium: Potential Implications. AB - RATIONALE: Gamma aminobutyric acid (GABA), a neurotransmitter of the central nervous system, is found in the systemic circulation of humans at a concentration between 0.5 and 3 MUmol/L. However, the potential source of circulating GABA and its significance on the vascular system remains unknown. We hypothesized that endothelial cells (ECs) may synthesize and release GABA to modulate some functions in the EC and after its release into the circulation. OBJECTIVE: To assess whether GABA is synthesized and released by the EC and its potential functions. METHODS AND RESULTS: Utilizing the human umbilical vein ECs and aortic ECs, we demonstrated for the first time that ECs synthesize and release GABA from [1-(14)C]glutamate. Localization of GABA and the presence of the GABA synthesizing enzyme, glutamic acid decarboxylase in EC were confirmed by immunostaining and immunoblot analysis, respectively. The presence of GABA was further confirmed by immunohistochemistry in the EC lining the human coronary vessel. EC-derived GABA regulated the key mechanisms of ATP synthesis, fatty acid, and pyruvate oxidation in EC. GABA protected EC by inhibiting the reactive oxygen species generation and prevented monocyte adhesion by attenuating vascular cell adhesion molecule -1 and monocyte chemoattractant protein-1 expressions. GABA had no relaxing effect on rat aortic rings. GABA exhibited a dose-dependent fall in blood pressure. However, the fall in BP was abolished after pretreatment with pentolinium. CONCLUSIONS: Our findings indicate novel potential functions of endothelium-derived GABA. PMID- 27354211 TI - Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity. AB - RATIONALE: Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood. OBJECTIVE: We set out to identify factors that promote arterial endothelial cell fate in vivo. METHODS AND RESULTS: We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic alpha1 and alpha2 receptors. CONCLUSIONS: These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease. PMID- 27354213 TI - Is viscoelastic coagulation monitoring with ROTEM or TEG validated? AB - Recent years have seen increasing worldwide interest in the use of viscoelastic coagulation monitoring tests, performed using devices such as ROTEM and TEG. The use of such tests to guide haemostatic therapy may help reduce transfusion of allogeneic blood products in bleeding patients and is supported in European guidelines for managing trauma and severe perioperative bleeding. In addition, viscoelastic tests form the basis of numerous published treatment algorithms. However, some publications have stated that viscoelastic tests are not validated. A specific definition of the term validation is lacking and regulatory requirements of the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have been fulfilled by ROTEM and TEG assays. Viscoelastic tests have been used in pivotal clinical trials, and they are approved for use in most of the world's countries. Provided that locally approved indications are adhered to, the regulatory framework for clinicians to use viscoelastic tests in routine clinical practice is in place. PMID- 27354212 TI - ADAM10-Dependent Signaling Through Notch1 and Notch4 Controls Development of Organ-Specific Vascular Beds. AB - RATIONALE: Endothelial Notch signaling is critical for early vascular development and survival. Yet, previously described mice lacking endothelial a disintegrin and metalloproteinase 10 (ADAM10), a key regulator of Notch signaling, survived into adulthood with organ-specific vascular defects. These findings raised questions about whether these vascular defects were related to Notch signaling or other functions of ADAM10. OBJECTIVE: The aims of the study are to determine whether compensatory or redundant functions of ADAM17 in Notch signaling can explain the survival of Adam10DeltaEC mice, explore the contribution of different Tie2-Cre transgenes to the differences in survival, and establish whether the Adam10DeltaEC vascular phenotypes can be recapitulated by inactivation of Notch receptors in endothelial cells. METHODS AND RESULTS: Mice lacking ADAM10 and ADAM17 in endothelial cells (Adam10/Adam17DeltaEC), which survived postnatally with organ-specific vascular defects, resembled Adam10DeltaEC mice. In contrast, Adam10DeltaEC mice generated with the Tie2Cre transgene previously used to inactivate endothelial Notch (Adam10DeltaEC(Flv)) died by E10.5. Quantitative polymerase chain reaction analysis demonstrated that Cre-mediated recombination occurs earlier in Adam10DeltaEC(Flv) mice than in the previously described Adam10DeltaEC mice. Finally, mice lacking endothelial Notch1 (Notch1DeltaEC) share some organ-specific vascular defects with Adam10DeltaEC mice, whereas Notch4(-/-) mice lacking endothelial Notch1 (Notch1DeltaEC/Notch4(-/-)) had defects in all vascular beds affected in Adam10DeltaEC mice. CONCLUSIONS: Our results argue against a major role for ADAM17 in endothelial Notch signaling and clarify the difference in phenotypes of previously described mice lacking ADAM10 or Notch in endothelial cells. Most notably, these findings uncover new roles for Notch signaling in the development of organ-specific vascular beds. PMID- 27354214 TI - Partial Superficial Parotidectomy With Retrograde Dissection of the Facial Nerve for Clinically "Benign" Parotid Tumors. AB - BACKGROUND: To review experience with partial superficial parotidectomy (PSP) and retrograde dissection of the facial nerve as a treatment for benign parotid tumors. METHODS: Retrospective cohort study of all patients presenting with a suspected benign primary parotid tumor undergoing parotid surgery. RESULTS: There were 214 cases retrieved. Postoperative facial nerve weakness occurred in 33% of patients; all were temporary. Increased extent of surgical resection (P < .001), deeper tumors (P = .05), and close tumor proximity to the facial nerve (P = .007) significantly correlated with postoperative facial weakness. The surgical margin was clear in 54%; 31% had capsule exposed in at least 1 point, and 13.5% had tumor at the margin. Cases with close proximity of tumor to facial nerve were more likely to have tumor at the margin (P = .034). CONCLUSION: Partial superficial parotidectomy with retrograde dissection is a suitable method for benign appearing parotid tumors. PMID- 27354215 TI - Quantitative Evaluation of Adult Subglottic Stenosis Using Intraoperative Long range Optical Coherence Tomography. AB - OBJECTIVES: To determine the feasibility of long-range optical coherence tomography (LR-OCT) as a tool to intraoperatively image and measure the subglottis and trachea during suspension microlaryngoscopy before and after endoscopic treatment of subglottic stenosis (SGS). METHODS: Long-range optical coherence tomography of the adult subglottis and trachea was performed during suspension microlaryngoscopy before and after endoscopic treatment for SGS. The anteroposterior and transverse diameters, cross-sectional area (CSA), distance from the vocal cords, and length of the SGS were measured using a MATLAB software. Pre-intervention and postintervention airway dimensions were compared. Three-dimensional volumetric airway reconstructions were generated using medical image processing software (MIMICS). RESULTS: Intraoperative LR-OCT imaging was performed in 3 patients undergoing endoscopic management of SGS. Statistically significant differences in mean anteroposterior diameter (P < .01), transverse diameter (P < .001), and CSA (P < .001) were noted between pre-intervention and postintervention data. Three-dimensional airway models were viewed in cross sectional format and via virtual "fly through" bronchoscopy. CONCLUSIONS: This is the first report of intraoperative LR-OCT of the subglottic and tracheal airway before and after surgical management of SGS in humans. Long-range optical coherence tomography offers a practical means to measure the dimensions of SGS and acquire objective data on the response to endoscopic treatment of SGS. PMID- 27354216 TI - Neutralizing capacity of inhibitors on FVIII is lower for natural FVIII/VWF complex than for isolated FVIII: in vitro comparative study in eleven different therapeutic FVIII concentrates. PMID- 27354217 TI - AMP-Activated Protein Kinase Suppresses Autoimmune Central Nervous System Disease by Regulating M1-Type Macrophage-Th17 Axis. AB - The AMP-activated protein kinase, AMPK, is an energy-sensing, metabolic switch implicated in various metabolic disorders; however, its role in inflammation is not well defined. We have previously shown that loss of AMPK exacerbates experimental autoimmune encephalomyelitis (EAE) disease severity. In this study, we investigated the mechanism through which AMPK modulates inflammatory disease like EAE. AMPKalpha1 knockout (alpha1KO) mice with EAE showed severe demyelination and inflammation in the brain and spinal cord compared with wild type due to higher expression of proinflammatory Th17 cytokines, including IL-17, IL-23, and IL-1beta, impaired blood-brain barrier integrity, and increased infiltration of inflammatory cells in the CNS. Infiltrated CD4 cells in the brains and spinal cords of alpha1KO with EAE were significantly higher compared with wild-type EAE and were characterized as IL-17 (IL-17 and GM-CSF double positive) CD4 cells. Increased inflammatory response in alpha1KO mice was due to polarization of macrophages (Mphi) to proinflammatory M1 type phenotype (IL 10(low)IL-23/IL-1beta/IL-6(high)), and these M1 Mphi showed stronger capacity to induce allogenic as well as Ag-specific (myelin oligodendrocyte glycoprotein [MOG]35-55) T cell response. Mphi from alpha1KO mice also enhanced the encephalitogenic property of MOG35-55-primed CD4 T cells in B6 mice. The increased encephalitogenic MOG-restricted CD4(+) T cells were due to an autocrine effect of IL-1beta/IL-23-mediated induction of IL-6 production in alpha1KO Mphi, which in turn induce IL-17 and GM-CSF production in CD4 cells. Collectively, our data indicate that AMPK controls the inflammatory disease by regulating the M1 phenotype-Th17 axis in an animal model of multiple sclerosis. PMID- 27354218 TI - FAT10 Is Critical in Influenza A Virus Replication by Inhibiting Type I IFN. AB - The H5N1 avian influenza virus causes severe disease and high mortality, making it a major public health concern worldwide. The virus uses the host cellular machinery for several steps of its life cycle. In this report, we observed overexpression of the ubiquitin-like protein FAT10 following live H5N1 virus infection in BALB/c mice and in the human respiratory epithelial cell lines A549 and BEAS-2B. Further experiments demonstrated that FAT10 increased H5N1 virus replication and decreased the viability of infected cells. Total RNA extracted from H5N1 virus-infected cells, but not other H5N1 viral components, upregulated FAT10, and this process was mediated by the retinoic acid-induced protein I-NF kappaB signaling pathway. FAT10 knockdown in A549 cells upregulated type I IFN mRNA expression and enhanced STAT1 phosphorylation during live H5N1 virus infection. Taken together, our data suggest that FAT10 was upregulated via retinoic acid-induced protein I and NF-kappaB during H5N1 avian influenza virus infection. And the upregulated FAT10 promoted H5N1 viral replication by inhibiting type I IFN. PMID- 27354220 TI - Detection of Pathogens in Blood for Diagnosis of Sepsis and Beyond. PMID- 27354219 TI - TLR9 Deficiency Leads to Accelerated Renal Disease and Myeloid Lineage Abnormalities in Pristane-Induced Murine Lupus. AB - Systemic lupus erythematosus (SLE) is a chronic, life-threatening autoimmune disorder, leading to multiple organ pathologies and kidney destruction. Analyses of numerous murine models of spontaneous SLE have revealed a critical role for endosomal TLRs in the production of autoantibodies and development of other clinical disease manifestations. Nevertheless, the corresponding TLR9-deficient autoimmune-prone strains consistently develop more severe disease pathology. Injection of BALB/c mice with 2,6,10,14-tetramethylpentadecane (TMPD), commonly known as pristane, also results in the development of SLE-like disease. We now show that Tlr9(-/-) BALB/c mice injected i.p. with TMPD develop more severe autoimmunity than do their TLR-sufficient cohorts. Early indications include an increased accumulation of TLR7-expressing Ly6C(hi) inflammatory monocytes at the site of injection, upregulation of IFN-regulated gene expression in the peritoneal cavity, and an increased production of myeloid lineage precursors (common myeloid progenitors and granulocyte myeloid precursors) in the bone marrow. TMPD-injected Tlr9(-/-) BALB/c mice develop higher autoantibody titers against RNA, neutrophil cytoplasmic Ags, and myeloperoxidase than do TMPD injected wild-type BALB/c mice. The TMP-injected Tlr9(-/-) mice, and not the wild type mice, also develop a marked increase in glomerular IgG deposition and infiltrating granulocytes, much more severe glomerulonephritis, and a reduced lifespan. Collectively, the data point to a major role for TLR7 in the response to self-antigens in this model of experimental autoimmunity. Therefore, the BALB/c pristane model recapitulates other TLR7-driven spontaneous models of SLE and is negatively regulated by TLR9. PMID- 27354221 TI - Thomas Willis Lecture: Is Translational Stroke Research Broken, and if So, How Can We Fix It? AB - Based on research, mainly in rodents, tremendous progress has been made in our basic understanding of the pathophysiology of stroke. After many failures, however, few scientists today deny that bench-to-bedside translation in stroke has a disappointing track record. I here summarize many measures to improve the predictiveness of preclinical stroke research, some of which are currently in various stages of implementation: We must reduce preventable (detrimental) attrition. Key measures for this revolve around improving preclinical study design. Internal validity must be improved by reducing bias; external validity will improve by including aged, comorbid rodents of both sexes in our modeling. False-positives and inflated effect sizes can be reduced by increasing statistical power, which necessitates increasing group sizes. Compliance to reporting guidelines and checklists needs to be enforced by journals and funders. Customizing study designs to exploratory and confirmatory studies will leverage the complementary strengths of both modes of investigation. All studies should publish their full data sets. On the other hand, we should embrace inevitable NULL results. This entails planning experiments in such a way that they produce high-quality evidence when NULL results are obtained and making these available to the community. A collaborative effort is needed to implement some of these recommendations. Just as in clinical medicine, multicenter approaches help to obtain sufficient group sizes and robust results. Translational stroke research is not broken, but its engine needs an overhauling to render more predictive results. PMID- 27354222 TI - Stroke in Duchenne Muscular Dystrophy: A Retrospective Longitudinal Study in 54 Patients. AB - BACKGROUND AND PURPOSE: Duchenne muscular dystrophy (DMD) is the most frequent skeletal muscle myopathy. Nearly all patients develop cardiomyopathy in their second decade of life. The purpose of this study was to evaluate the frequency, cause, and outcome of stroke in a German cohort of patients with DMD. METHODS: Retrospective analysis of medical records of 54 DMD patients, who lived in a regional facility for handicapped people (Wichernhaus Altdorf, Germany) between 1963 and 2013. RESULTS: Fifty-four DMD patients were followed up for 7.4 years on average. Mean age at admission and discharge from the long-term care facility or death were 11.4 and 18.8 years, respectively. Covering a total observation period of 400 patient-years, we identified 4 DMD patients with juvenile arterial ischemic strokes. Off-label systemic thrombolysis in 2 patients resulted in a nearly complete regression of stroke-related symptoms, but 1 patient died of septic pneumonia and cardiac failure 24 days after thrombolysis therapy. In the other 2 patients, who had their ischemic strokes in 1994 and 1998, severe infarction-related symptoms persisted, and 1 patient died 13 days later. DMD associated cardiomyopathy without evidence of atrial fibrillation was the only risk factor for ischemic stroke in all patients. CONCLUSIONS: This study indicates an increased risk for ischemic strokes in DMD patients. Regular cardiological assessment of all DMD patients is mandatory to evaluate the individual risk profile for cardioembolic events and to adapt therapeutic strategies. PMID- 27354223 TI - Tissue-Type Plasminogen Activator-A296-299 Prevents Impairment of Cerebral Autoregulation After Stroke Through Lipoprotein-Related Receptor-Dependent Increase in cAMP and p38. AB - BACKGROUND AND PURPOSE: The sole Food and Drug Administration-approved treatment for stroke is tissue-type plasminogen activator (tPA), but its brief therapeutic window and complications of treatment constrain its use. One limitation may be its potential to exacerbate impairment of cerebral autoregulation after stroke. Vasodilation is maintained by elevations in cAMP. However, cAMP levels fall after stroke because of overactivation of N-methyl-d-aspartate receptors by toxic levels of glutamate, an effect that is exacerbated by tPA. Binding of wild-type (wt) tPA to the low-density lipoprotein-related receptor (LRP) mediates dilation. We propose that binding of wt-tPA to N-methyl-d-aspartate receptor reduces cAMP and impairs vasodilation. We hypothesize that tPA-A(296-299), a variant that is fibrinolytic but cannot bind to N-methyl-d-aspartate receptor, preferentially binds to LRP and increases cAMP and p38, limiting autoregulation impairment after stroke. METHODS: Stroke was induced by photothrombosis in pigs equipped with a closed cranial window, cerebral blood flow determined by microspheres, and cerebrospinal fluid cAMP and p38 determined by ELISA. RESULTS: Stroke decreased cerebral blood flow. Cerebral blood flow was reduced further during hypotension, indicating impairment of autoregulation. Autoregulation was further impaired by wt-tPA, which was prevented by MK801 and tPA-A(296-299). Protection by tPA-A(296 299) was blocked by anti-LRP Ab, the LRP antagonist receptor-associated protein, and the p38 inhibitor SB 203580, but not by control IgG. Stroke reduced cerebrospinal fluid cAMP, which was reduced further by wt-tPA, but augmented by tPA-A(296-299). Cerebrospinal fluid p38 was unchanged by wt-tPA, increased by tPA A(296-299), and decreased by anti-LRP Ab and receptor-associated protein. CONCLUSIONS: tPA-A(296-299) prevents impairment of cerebral autoregulation after stroke through an LRP-dependent increase in cAMP and p38. PMID- 27354225 TI - Diagnostic Yield and Safety of Brain Biopsy for Suspected Primary Central Nervous System Angiitis. AB - BACKGROUND AND PURPOSE: The utility and safety of brain biopsy for suspected primary angiitis of the central nervous system (PACNS) are uncertain. Factors predictive of a positive biopsy have not been well described. Our aim was to evaluate the diagnostic yield and safety of brain biopsy in suspected PACNS and determine whether any prebiopsy variables are associated with a positive biopsy. METHODS: This is a retrospective study of consecutive patients who underwent diagnostic brain biopsy for PACNS at a single institution. The relationship between biopsy yield and patient demographics, surgical technique, laboratory testing, neuroimaging, biopsy characteristics, and prebiopsy immunosuppressive therapy were examined. RESULTS: PACNS was confirmed in 9 of 79 patients (11%). Biopsy identified alternative diagnoses in 24 patients (30%), with cerebral amyloid angiopathy (8 patients), encephalitis (5 patients), demyelination (3 patients), and CNS lymphoma (3 patients) most commonly found. There was no correlation between a positive biopsy and cerebrospinal fluid results, neuroimaging, surgical technique, biopsy characteristics, or preoperative immunosuppressive therapy. Smaller biopsies (P=0.02) and closed procedures (P=0.013) were less likely to yield a diagnosis. Postoperative complications occurred in 13 patients (16%), 3 (4%) of which were serious. CONCLUSIONS: Brain biopsy leads to pathological confirmation of vasculitis in a minority of suspected PACNS cases but alternative diagnoses are often identified. Importantly, rare but meaningful complications may occur. PMID- 27354224 TI - Left Ventricular Ejection Fraction and Risk of Stroke and Cardiac Events in Heart Failure: Data From the Warfarin Versus Aspirin in Reduced Ejection Fraction Trial. AB - BACKGROUND AND PURPOSE: In heart failure (HF), left ventricular ejection fraction (LVEF) is inversely associated with mortality and cardiovascular outcomes. Its relationship with stroke is controversial, as is the effect of antithrombotic treatment. We studied the relationship of LVEF with stroke and cardiovascular events in patients with HF and the effect of different antithrombotic treatments. METHODS: In the Warfarin Versus Aspirin in Reduced Ejection Fraction (WARCEF) trial, 2305 patients with systolic HF (LVEF<=35%) and sinus rhythm were randomized to warfarin or aspirin and followed for 3.5+/-1.8 years. Although no differences between treatments were observed on primary outcome (death, stroke, or intracerebral hemorrhage), warfarin decreased the stroke risk. The present report compares the incidence of stroke and cardiovascular events across different LVEF and treatment subgroups. RESULTS: Baseline LVEF was inversely and linearly associated with primary outcome, mortality and its components (sudden and cardiovascular death), and HF hospitalization, but not myocardial infarction. A relationship with stroke was only observed for LVEF of <15% (incidence rates: 2.04 versus 0.95/100 patient-years; P=0.009), which more than doubled the adjusted stroke risk (adjusted hazard ratio, 2.125; 95% CI, 1.182-3.818; P=0.012). In warfarin-treated patients, each 5% LVEF decrement significantly increased the stroke risk (adjusted hazard ratio, 1.346; 95% CI, 1.044-1.737; P=0.022; P value for interaction=0.04). CONCLUSIONS: In patients with systolic HF and sinus rhythm, LVEF is inversely associated with death and its components, whereas an association with stroke exists for very low LVEF values. An interaction with warfarin treatment on stroke risk may exist. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938. PMID- 27354226 TI - Transduction of hematopoietic stem cells to stimulate RNA interference against feline infectious peritonitis. AB - Objectives The goals of the study were: (1) to develop and evaluate non replicating lentivirus vectors coding for feline coronavirus (FCoV)-specific micro (mi)RNA as a potential antiviral therapy for feline infectious peritonitis (FIP); (2) to assess the feasibility of transducing hematopoietic stem cells (HSCs) with ex vivo introduction of the miRNA-expressing lentivirus vector; and (3) to assess the ability of the expressed miRNA to inhibit FCoV replication in HSCs in vitro. Methods HSCs were obtained from feline bone marrow and replicated in vitro. Three lentiviruses were constructed, each expressing a different anti FCoV miRNA. HSCs were stably transduced with the miRNA-expressing lentivirus vector that produced the most effective viral inhibition in a feline cell line. The effectiveness of the transduction and the expression of anti-FCoV miRNA were tested by infecting the HSCs with two different strains of FCoV. The inhibition of coronavirus replication was determined by relative quantification of the inhibition of intracellular viral genomic RNA synthesis using real-time, reverse transcription PCR. The assessment of virus replication inhibition was determined via titration of extracellular virus using the TCID50 assay. Results Inhibition of FCoV was most significant in feline cells expressing miRNA-L2 that targeted the viral leader sequence, 48 h postinfection. miRNA-L2 expression in stably transduced HSCs resulted in 90% and 92% reductions in FIPV WSU 79-1146 genomic RNA synthesis and extracellular virus production, respectively, as well as 74% and 80% reduction in FECV WSU 79-1683 genomic RNA synthesis and extracellular virus production, respectively, as compared with an infected negative control sample producing non-targeting miRNA. Conclusions and relevance These preliminary results show that genetic modification of HSCs for constitutive production of anti-coronavirus miRNA will reduce FCoV replication. PMID- 27354227 TI - Can clinical signs, clinicopathological findings and abdominal ultrasonography predict the site of histopathological abnormalities of the alimentary tract in cats? PMID- 27354228 TI - Combined physeal fractures of the distal radius and ulna: complications associated with K-wire fixation and long-term prognosis in six cats. AB - Objectives The objective was to describe the complications and long-term outcome associated with Kirschner (K)-wire fixation of combined distal radial and ulnar physeal fractures in six cats. Methods Medical records (2002-2014) of six referral institutions were searched for cats with combined distal radial and ulnar physeal fractures. Cases with complete clinical files, radiographs and surgical records were retrospectively reviewed. Long-term outcome was assessed via telephone interviews using an owner questionnaire. Results Complete files were available for 6/9 identified cases (cases 1-6). All fractures were classified as Salter-Harris type I or II. Five cases underwent open reduction and internal fixation via cross-pinning of the distal radius and intramedullary pinning of the ulna (cases 1-3); fixation of the distal radial and ulnar physes with one K-wire each (case 4); and K-wire fixation of the radial physis in combination with two transulnoradial K-wires (case 5). One case underwent closed reduction and percutaneous cross-pinning of the distal radius under fluoroscopic guidance (case 6). The complications encountered were: reduced radiocarpal range of motion (ROM) (cases 1, 3, 4, 5); implant loosening/migration (cases 1, 2, 5); and radioulnar synostosis (case 4). None of the cats developed angular limb deformity. Long-term outcome (12 months to 7 years after surgery) was graded as 'excellent' by the owners in all cases. Conclusions and relevance Prognosis is favourable for feline combined distal radial and ulnar physeal fractures following K-wire fixation in cats over 7 months of age. Implant removal after bony union is recommended to minimise reduction in ROM and to prevent implant loosening/migration. PMID- 27354229 TI - Load effect on background rhythms during motor execution: A magnetoencephalographic study. AB - We investigated the effect of load against self-paced movement on cortical involvement for motor execution. Ten right-handed healthy volunteers were requested to perform brisk extension of the right index finger at self-paced intervals exceeding 10s for three load conditions: 0g, 50g and 100g. Movement related magnetic fields were recorded using an MEG system. The signals were band pass-filtered through 18-23Hz and rectified before averaging with respect to EMG onset. We analyzed the time course and %change of peak amplitude with reference to the baseline amplitude in event-related desynchronization (ERD) or synchronization (ERS) in each hemisphere. Maximum response was observed around the left somatomotor area for all conditions. ERD did not show any significant difference before the movement onset among the three load conditions. For %change, ERS in the post-movement period was significantly larger for the 100g load condition than for the 0g load condition, and that was significantly greater over the left than over the right hemisphere. These findings indicate that the load has little effect on pre-movement desynchronization, whereas it affects the post-movement synchronization on background rhythms. PMID- 27354230 TI - Abnormal wake/sleep pattern in a novel gain-of-function model of DISC1. AB - Sleep disturbances are common in psychiatric disorders, but the causal relationship between the two and the underlying genetic factors is unclear. The DISC1 gene is strongly linked to mood disorders and schizophrenia in a Scottish pedigree. In an earlier study we found a sleep homeostasis disturbance in a Drosophila model overexpressing wild-type human DISC1. Here we aimed to explore the relationship between sleep and the DISC1 gene in a mammalian model, a novel transgenic mouse model expressing full-length human DISC1. We assessed circadian rhythms by monitoring wheel running activity under normal 24-h light:dark conditions and in constant darkness and found the DISC1 mice to have normal circadian photoentrainment and normal intrinsic circadian period. We also assessed sleep duration and quality in the DISC1 mice and found that they were awake longer than wild-type controls at baseline with a tendency for lower rebound of delta activity during recovery from a short sleep deprivation. Thus we suggest that DISC1 may be involved in sleep regulation. PMID- 27354231 TI - Steady State Ocean Response to Wind Forcing in Extratropical Frontal Regions. AB - In regions of strong sea surface temperature (SST) gradients, the surface "geostrophic" currents have a vertical shear aligned with the surface density front defined by the temperature. This surface geostrophic ("thermal wind") shear can balance a portion of the surface wind stress, altering the classic Ekman response to wind forcing. Here we show that these frontal effects cannot be ignored in the Tropics or in strong frontal regions in the extratropics, such as found in coastal regions and in western boundary currents of all basins. Frontal effects also dominate the classic Ekman response in the regions of both hemispheres where Trade winds change to westerlies. Implications for vertical motion and global heat transport are discussed. PMID- 27354232 TI - Loss of ARID1A expression predicts poor survival prognosis in gastric cancer: a systematic meta-analysis from 14 studies. AB - The chromatin remodeling gene, AT-rich interactive domain 1A gene (ARID1A), frequently mutates inactively in gastric cancer (GC). However, its prognostic value remains controversial. To address this issue, a comprehensive meta-analysis was performed. Studies published until March 2016 were systematically searched. A total of 15 cohorts from 14 literatures involving 3183 patients were subjected to this meta-analysis. The pooled data showed that ARID1A expression loss predicted poor overall survival (OS) in GC (Hazard Ratio (HR) = 1.60; 95% Confidence Interval (CI) = 1.40-1.81; P < 0.001), with low heterogeneity among these studies (I(2) = 21.5%; P = 0.214). Stratification analyses revealed that ARID1A expression loss was associated with poor OS in Asians (HR = 1.65, 95% CI = 1.44 1.89), proportion of proximal disease <=30% subgroup (HR = 1.80, 95% CI = 1.36 2.38) and Epstein-Barr virus (EBV) (+) > 5% subgroup (HR = 1.59, 95% CI = 1.18 2.15). The robust results were suggested by sensitivity analyses and no evidence of significant publication bias was detected. This study demonstrated a significant relationship between deletion of ARID1A expression and poor OS in GC. Moreover, ethnicity, tumor location and EBV infection status might be potential key factors influencing this correlation. PMID- 27354233 TI - Biosimilars: Extrapolation for oncology. AB - A biosimilar is a biologic that is highly similar to a licensed biologic (the reference product) in terms of purity, safety and efficacy. If the reference product is licensed to treat multiple therapeutic indications, extrapolation of indications, i.e., approval of a biosimilar for use in an indication held by the reference product but not directly studied in a comparative clinical trial with the biosimilar, may be possible but has to be scientifically justified. Here, we describe the data required to establish biosimilarity and emphasize that indication extrapolation is based on scientific principles and known mechanism of action. PMID- 27354234 TI - Network Support II: Randomized controlled trial of Network Support treatment and cognitive behavioral therapy for alcohol use disorder. AB - BACKGROUND: The social network of those treated for alcohol use disorder can play a significant role in subsequent drinking behavior, both for better and worse. Network Support treatment was devised to teach ways to reconstruct social networks so that they are more supportive of abstinence and less supportive of drinking. For many patients this may involve engagement with AA, but other strategies are also used. PURPOSE: The current trial of Network Support treatment, building on our previous work, was intended to further enhance the ability of patients to construct abstinence-supportive social networks, and to test this approach against a strong control treatment. METHODS: Patients were 193 men and women with alcohol use disorder recruited from the community and assigned to either 12 weeks of Network Support (NS) or Packaged Cognitive-Behavioral Treatment (PCBT), and followed for 27 months. RESULTS: Results of multilevel analyses indicated that NS yielded better posttreatment results in terms of both proportion of days abstinent and drinking consequences, and equivalent improvements in 90-day abstinence, heavy drinking days and drinks per drinking day. Mediation analyses revealed that NS treatment effects were mediated by pre post changes in abstinence self-efficacy and in social network variables, especially proportion of non-drinkers in the social network and attendance at Alcoholics Anonymous. CONCLUSION: It was concluded that helping patients enhance their abstinent social network can be effective, and may provide a useful alternative or adjunctive approach to treatment. PMID- 27354235 TI - A high-fat diet impairs cooling-evoked brown adipose tissue activation via a vagal afferent mechanism. AB - In dramatic contrast to rats on a control diet, rats maintained on a high-fat diet (HFD) failed to activate brown adipose tissue (BAT) during cooling despite robust increases in their BAT activity following direct activation of their BAT sympathetic premotor neurons in the raphe pallidus. Cervical vagotomy or blockade of glutamate receptors in the nucleus of the tractus solitarii (NTS) reversed the HFD-induced inhibition of cold-evoked BAT activity. Thus, a HFD does not prevent rats from mounting a robust, centrally driven BAT thermogenesis; however, a HFD does alter a vagal afferent input to NTS neurons, thereby preventing the normal activation of BAT thermogenesis to cooling. These results, paralleling the absence of cooling-evoked glucose uptake in the BAT of obese humans, reveal a neural mechanism through which consumption of a HFD contributes to reduced energy expenditure and thus to weight gain. PMID- 27354236 TI - Novel insights into development of diabetic bladder disorder provided by metabolomic analysis of the rat nondiabetic and diabetic detrusor and urothelial layer. AB - There are at present no published studies providing a global overview of changes in bladder metabolism resulting from diabetes. Such studies have the potential to provide mechanistic insight into the development of diabetic bladder disorder (DBD). In the present study, we compared the metabolome of detrusor and urothelial layer in a 1-mo streptozotocin-induced rat model of type 1 diabetes with nondiabetic controls. Our studies revealed that diabetes caused both common and differential changes in the detrusor and urothelial layer's metabolome. Diabetes resulted in similar changes in the levels of previously described diabetic markers in both tissues, such as glucose, lactate, 2-hydroxybutyrate, branched-chain amino acid degradation products, bile acids, and 1,5 anhydroglucitol, as well as markers of oxidative stress. In the detrusor (but not the urothelial layer), diabetes caused activation of the pentose-phosphate and polyol pathways, concomitant with a reduction in the TCA cycle and beta oxidation. Changes in detrusor energy-generating pathways resulted in an accumulation of sorbitol that, through generation of advanced glycation end products, is likely to play a central role in the development of DBD. In the diabetic urothelial layer there was decreased flux of glucose via glycolysis and changes in lipid metabolism, particularly prostaglandin synthesis, which also potentially contributes to detrusor dysfunction. PMID- 27354237 TI - Elevated expression of the Sertoli cell androgen receptor disrupts male fertility. AB - Recently, we created a unique gain-of-function mouse model with Sertoli cell specific transgenic androgen receptor expression (TgSCAR) showing that SCAR activity controls the synchronized postnatal development of somatic Sertoli and Leydig cells and meiotic-postmeiotic germ cells. Moderate TgSCAR (TgSCAR(m)) expression reduced testis size but had no effect on male fertility. Here, we reveal that higher TgSCAR expression (TgSCAR(H)) causes male infertility. Higher SCAR activity, shown by upregulated AR-dependent transcripts (Rhox5, Spinw1), resulted in smaller adult TgSCAR(H) testes (50% of normal) despite normal or elevated circulating and intratesticular testosterone levels. Unlike fertile TgSCAR(m) males, testes of adult TgSCAR(H) males exhibited focal regions of interstitial hypertrophy featuring immature adult Leydig cells and higher intratesticular dihydrotestosterone and 5alpha-androstane 3alpha,17beta-diol levels that are normally associated with pubertal development. Mature TgSCAR(H) testes also exhibited markedly reduced Sertoli cell numbers (70%), although meiotic and postmeiotic germ cell/Sertoli cell ratios were twofold higher than normal, suggesting that elevated TgSCAR activity supports excessive spermatogenic development. Concurrent with the higher germ cell load of TgSCAR(H) Sertoli cells were increased levels of apoptotic germ cells in TgSCAR(H) relative to TgSCAR(m) testes. In addition, TgSCAR(H) testes displayed unique morphological degeneration that featured accumulated cellular and spermatozoa clusters in dilated channels of rete testes, consistent with reduced epididymal sperm numbers. Our findings reveal for the first time that excessive Sertoli cell AR activity in mature testes can reach a level that disturbs Sertoli/germ cell homeostasis, impacts focal Leydig cell function, reduces sperm output, and disrupts male fertility. PMID- 27354239 TI - C-type Lectin Receptor Expression on Human Basophils and Effects of Allergen Specific Immunotherapy. AB - Basophils are emerging as immunoregulatory cells capable of interacting with their environment not only via their characteristic IgE-mediated activation, but also in an IgE-independent manner. Basophils are known to express and respond to stimulation via TLR2, TLR4, DC-SIGN and DCIR, but whether basophils also express other C-type lectin receptors (CLRs) is largely unknown. In this study, we investigate the CLR expression profile of human basophils using multicolour flow cytometry. As FcRs as well as some CLRs are associated with allergen recognition and shown to be involved in subsequent immune responses, the expression of CLRs and FcRs on peripheral blood basophils, as well as their frequency, was monitored for 1 year in subjects undergoing subcutaneous allergen-specific immunotherapy (AIT). Here, we show that human basophils express CLECSF14, DEC205, Dectin-1, Dectin-2 and MRC2. Furthermore, we demonstrate that the frequencies of basophils expressing the allergy-associated CLRs Dectin-1 and Dectin-2 were significantly reduced after 1 year and 8 weeks of AIT, respectively. In contrast, the frequency of basophils positive for FcgammaRII, as well as the fraction of total basophils, significantly increased after 1 year of AIT. The herein demonstrated expression of various CLRs on basophils, and their altered CLR and FcR expression profile upon AIT, suggest yet unexplored ways by which basophils can interact with antigens and may point to novel immunoregulatory functions targeted through AIT. PMID- 27354240 TI - Thermal unfolding simulations of NBD1 domain variants reveal structural motifs associated with the impaired folding of F508del-CFTR. AB - We employed high-temperature classical molecular dynamics (MD) simulations to investigate the unfolding process of the wild-type (WT) and F508del-NBD1 domains of CFTR protein, with and without second-site mutations. To rationalize the in vitro behavior of F508del-NBD1, namely its lower folding yield and higher aggregation propensity, we focused our analysis of the MD data on the existence of intermediate states with aggregation potential and/or stabilized by a significant number of non-native interactions (i.e. misfolded states). We find that the deletion of phenylalanine 508 is able to forcefully reshape the conformational space of the NBD1 domain to the extent that it uniquely populates intermediate states whose structural traits provide important insights into the molecular events that underlie the impaired folding of F508del-NBD1. In particular, our simulations predict the formation of a misfolded intermediate whose population is highly enhanced by deletion of residue 508. The stabilization of this intermediate is a direct consequence of the enhanced non-native coupling between various key regions of the alpha-helical subdomain and ATP-binding subdomain; it is singularly characterized by a set of non-native interactions within the ATP-binding subdomain and between that domain and the alpha-helical subdomain region. The formation of this intermediate is not blocked by second site suppressor mutations which indicates a limited role of the latter in correcting the rather complex folding process of the CFTR protein missing residue 508. PMID- 27354241 TI - Electronic and chiroptical properties of chiral cycloiridiated complexes bearing helicenic NHC ligands. AB - The first helicene-NHC-iridium complexes have been prepared in enantiopure forms. Their stereochemical, electronic, and chiroptical features were characterized experimentally and via first-principles calculations, highlighting the helical and iridium-centered chirality. PMID- 27354242 TI - Oro-dental features of Pallister-Killian syndrome: Evaluation of 21 European probands. AB - Pallister-Killian syndrome (PKS) is a rare sporadic multi-systemic developmental disorder caused by a mosaic tetrasomy of the short arm of chromosome 12. A wide range of clinical characteristics including intellectual disability, seizures, and congenital malformations has previously been described. Individuals with PKS show a characteristic facial phenotype with frontal bossing, alopecia, sparse eyebrows, depressed nasal bridge, long philtrum, telecanthus, and posteriorly rotated ears. Oro-dental features, such as "Pallister lip," macroglossia, delayed eruption of primary teeth, high arched-palate, prognathism, and cleft palate have been occasionally reported in the medical literature. The aim of the study was to assess the oro-dental phenotype of PKS and to describe the oral health status in a cohort participating in the First European Workshop on PKS. A clinical dental examination was performed in 21 Caucasian probands and data regarding medical and dental history collected. Twelve probands (57%) showed an atypical dental pattern, with multiple missing teeth (primarily the first permanent molars) and 2 (10%) a double teeth. The severity of gingivitis and dental caries increased with age and gingival overgrowth was a common finding. A characteristic occlusive phenotype was found: a high-arched palate with mandibular prognathism associated with an anterior openbite and crossbite and with posterior crossbite (unilateral or bilateral). The prevalence of oral habits (non-nutritive sucking, mouth breathing, bruxism) was high, even in older probands. This study suggests that individuals affected by PKS should be observed closely for oro-dental diseases and a multidisciplinary approach is needed to implement the right preventive measures. (c) 2016 Wiley Periodicals, Inc. PMID- 27354243 TI - Magnetic assembly of transparent and conducting graphene-based functional composites. AB - Innovative methods producing transparent and flexible electrodes are highly sought in modern optoelectronic applications to replace metal oxides, but available solutions suffer from drawbacks such as brittleness, unaffordability and inadequate processability. Here we propose a general, simple strategy to produce hierarchical composites of functionalized graphene in polymeric matrices, exhibiting transparency and electron conductivity. These are obtained through protein-assisted functionalization of graphene with magnetic nanoparticles, followed by magnetic-directed assembly of the graphene within polymeric matrices undergoing sol-gel transitions. By applying rotating magnetic fields or magnetic moulds, both graphene orientation and distribution can be controlled within the composite. Importantly, by using magnetic virtual moulds of predefined meshes, graphene assembly is directed into double-percolating networks, reducing the percolation threshold and enabling combined optical transparency and electrical conductivity not accessible in single-network materials. The resulting composites open new possibilities on the quest of transparent electrodes for photovoltaics, organic light-emitting diodes and stretchable optoelectronic devices. PMID- 27354244 TI - Complementary and alternative medicine use for constipation: a critical review focusing upon prevalence, type, cost, and users' profile, perception and motivations. AB - OBJECTIVES: Complementary and alternative medicine (CAM) is increasingly used by those suffering from constipation. This paper reports the first critical integrative review of CAM use for people with constipation focusing upon the prevalence, type and cost of CAM use, as well as CAM users' profile, perception and motivations. METHODS: A comprehensive search of international literature was conducted in MEDLINE, Academic Search Complete (EBSCO), and Allied and Complementary Medicine Database (AMED). The search was limited to original research peer-reviewed English language articles concerning CAM use for constipation published with an abstract and full text between 2005 and 2015. RESULTS: A total of 35 papers met the inclusion criteria and were included in the review. The review shows approximately one in every three people suffering from constipation use CAM with herbal medicine the most commonly used CAM treatment for constipation and a large proportion of CAM use occurring concurrent with or in addition to conventional medical treatments. While early investigation suggests the cost of herbal medicine use in constipation care may be lower than that associated with the use other CAM modalities and conventional medications, this issue requires further research. CONCLUSIONS: Although a high percentage of people with constipation using CAM consider these treatments effective, there remains a need for further in-depth examination of both patient and provider perspectives as well as communication and decision-making around CAM use for constipation to inform safe, effective and coordinated care for patients with constipation. PMID- 27354238 TI - Biological underpinnings of breastfeeding challenges: the role of genetics, diet, and environment on lactation physiology. AB - Lactation is a dynamic process that has evolved to produce a complex biological fluid that provides nutritive and nonnutritive factors to the nursing offspring. It has long been assumed that once lactation is successfully initiated, the primary factor regulating milk production is infant demand. Thus, most interventions have focused on improving breastfeeding education and early lactation support. However, in addition to infant demand, increasing evidence from studies conducted in experimental animal models, production animals, and breastfeeding women suggests that a diverse array of maternal factors may also affect milk production and composition. In this review, we provide an overview of our current understanding of the role of maternal genetics and modifiable factors, such as diet and environmental exposures, on reproductive endocrinology, lactation physiology, and the ability to successfully produce milk. To identify factors that may affect lactation in women, we highlight some information gleaned from studies in experimental animal models and production animals. Finally, we highlight the gaps in current knowledge and provide commentary on future research opportunities aimed at improving lactation outcomes in breastfeeding women to improve the health of mothers and their infants. PMID- 27354246 TI - An evaluative conservative case for biomedical enhancement. AB - It is widely believed that a conservative moral outlook is opposed to biomedical forms of human enhancement. In this paper, I argue that this widespread belief is incorrect. Using Cohen's evaluative conservatism as my starting point, I argue that there are strong conservative reasons to prioritise the development of biomedical enhancements. In particular, I suggest that biomedical enhancement may be essential if we are to maintain our current evaluative equilibrium (ie, the set of values that undergird and permeate our current political, economic and personal lives) against the threats to that equilibrium posed by external, non biomedical forms of enhancement. I defend this view against modest conservatives who insist that biomedical enhancements pose a greater risk to our current evaluative equilibrium, and against those who see no principled distinction between the forms of human enhancement. PMID- 27354245 TI - Solidarity, justice and unconditional access to healthcare. AB - Luck egalitarianism provides a reason to object to conditionality in health incentive programmes in some cases when conditionality undermines political values such as solidarity or inclusiveness. This is the case with incentive programmes that aim to restrict access to essential healthcare services. Such programmes undermine solidarity. Yet, most people's lives are objectively worse, in one respect, in non-solidary societies, because solidarity contributes both instrumentally and directly to individuals' well-being. Because solidarity is non excludable, undermining it will deprive both the prudent and the imprudent citizens of its goods. Thereby, undermining solidarity can make prudent citizens worse off than they would have otherwise been, out of no fault or choice of their own, but rather as a result of somebody else's imprudent choice. This goes against the spirit of luck egalitarianism. Therefore (luck egalitarian) justice can require us to save the imprudent and avoid conditionality in access to essential healthcare services. PMID- 27354247 TI - Afterword: returning to philosophical foundations in research ethics. AB - This is an afterword to the JME symposium on the benefit/risk ratio challenge in clinical research, and the case of HIV cure. It notes implications of the symposium for research ethics in general. PMID- 27354248 TI - Too poor to say no? Health incentives for disadvantaged populations. AB - Incentive schemes, which offer recipients benefits if they meet particular requirements, are being used across the world to encourage healthier behaviours. From the perspective of equality, an important concern about such schemes is that since people often do not have equal opportunity to fulfil the stipulated conditions, incentives create opportunity for further unfair advantage. Are incentive schemes that are available only to disadvantaged groups less susceptible to such egalitarian concerns? While targeted schemes may at first glance seem well placed to help improve outcomes among disadvantaged groups and thus reduce inequalities, I argue in this paper that they are susceptible to significant problems. At the same time, incentive schemes may be less problematic when they operate in ways that differ from the 'standard' incentive mechanism; I discuss three such mechanisms. PMID- 27354249 TI - Lactobacillus crispatus inhibits the infectivity of Chlamydia trachomatis elementary bodies, in vitro study. AB - Lactobacillus species dominate the vaginal microbiota of healthy reproductive-age women and protect the genitourinary tract from the attack of several infectious agents. Chlamydia trachomatis, a leading cause of sexually transmitted disease worldwide, can induce severe sequelae, i.e. pelvic inflammatory disease, infertility and ectopic pregnancy. In the present study we investigated the interference of Lactobacillus crispatus, L. gasseri and L. vaginalis, known to be dominant species in the vaginal microbiome, with the infection process of C. trachomatis. Lactobacilli exerted a strong inhibitory effect on Chlamydia infectivity mainly through the action of secreted metabolites in a concentration/pH dependent mode. Short contact times were the most effective in the inhibition, suggesting a protective role of lactobacilli in the early steps of Chlamydia infection. The best anti-Chlamydia profile was shown by L. crispatus species. In order to delineate metabolic profiles related to anti-Chlamydia activity, Lactobacillus supernatants were analysed by (1)H-NMR. Production of lactate and acidification of the vaginal environment seemed to be crucial for the activity, in addition to the consumption of the carbonate source represented by glucose. The main conclusion of this study is that high concentrations of L. crispatus inhibit infectivity of C. trachomatis in vitro. PMID- 27354250 TI - Three-Dimensional Field Optimization Method: Gold-Standard Validation of a Novel Color Doppler Method for Quantifying Mitral Regurgitation. AB - BACKGROUND: Accurate diagnosis of mitral regurgitation (MR) severity is central to proper treatment. Although numerous approaches exist, an accurate, gold standard clinical technique remains elusive. The authors previously reported on the initial development and demonstration of the automated three-dimensional (3D) field optimization method (FOM) algorithm, which exploits 3D color Doppler ultrasound imaging and builds on existing MR quantification techniques. The aim of the present study was to extensively validate 3D FOM in terms of accuracy, ease of use, and repeatability. METHODS: Three-dimensional FOM was applied to five explanted ovine mitral valves in a left heart simulator, which were systematically perturbed to yield a total of 29 unique regurgitant geometries. Three-dimensional FOM was compared with a gold-standard flow probe, as well as the most clinically prevalent MR volume quantification technique, the two dimensional (2D) proximal isovelocity surface area (PISA) method. RESULTS: Overall, 3D FOM overestimated and 2D PISA underestimated MR volume, but 3D FOM error had smaller magnitude (5.2 +/- 9.9 mL) than 2D PISA error (-6.9 +/- 7.7 mL). Two-dimensional PISA remained superior in diagnosis for round orifices and especially mild MR, as predicted by ultrasound physics theory. For slit-type orifices and severe MR, 3D FOM showed significant improvement over 2D PISA. Three dimensional FOM processing was technically simpler and significantly faster than 2D PISA and required fewer ultrasound acquisitions. Three-dimensional FOM did not show significant interuser variability, whereas 2D PISA did. CONCLUSIONS: Three dimensional FOM may provide increased clinical value compared with 2D PISA because of increased accuracy in the case of complex or severe regurgitant orifices as well as its greater repeatability and simpler work flow. PMID- 27354251 TI - KymoRod: a method for automated kinematic analysis of rod-shaped plant organs. AB - A major challenge in plant systems biology is the development of robust, predictive multiscale models for organ growth. In this context it is important to bridge the gap between the, rather well-documented molecular scale and the organ scale by providing quantitative methods to study within-organ growth patterns. Here, we describe a simple method for the analysis of the evolution of growth patterns within rod-shaped organs that does not require adding markers at the organ surface. The method allows for the simultaneous analysis of root and hypocotyl growth, provides spatio-temporal information on curvature, growth anisotropy and relative elemental growth rate and can cope with complex organ movements. We demonstrate the performance of the method by documenting previously unsuspected complex growth patterns within the growing hypocotyl of the model species Arabidopsis thaliana during normal growth, after treatment with a growth inhibiting drug or in a mechano-sensing mutant. The method is freely available as an intuitive and user-friendly Matlab application called KymoRod. PMID- 27354252 TI - Effects of dietary phospholipid on lipase activity, antioxidant capacity and lipid metabolism-related gene expression in large yellow croaker larvae (Larimichthys crocea). AB - It was previously shown that lipid content of the whole larvae body fed the phospholipid (PL)-devoid diet was significantly lower than that of larvae fed PL supplemented diets (P<0.05) (Feng et al., unpublished results). The mechanisms involved remain unclear and were explored from the perspective of fatty acids delivery, uptake, synthesis and oxidation in the present study. Besides, this study was also designed to investigate the effect of dietary PL on antioxidant capacity in large yellow croaker larvae (Larimichthys crocea). Triplicate groups of larvae (initial body weight: 3.86+/-0.24mg) were fed three isonitrogenous and isolipidic diets with increasing levels of PL (2.53%, 6.32% and 12.7%) eight times daily for 30days. Results showed that the specific activities of superoxide dismutase and catalase were significantly higher in 12.7% PL group compared to those in 2.53% PL group (P<0.05), while an opposite trend was observed for MDA content (P<0.05). The specific activity of lipase and the mRNA abundance of fatty acids delivery and uptake-related genes, including lipoprotein lipase, hepatic lipase and fatty acids translocase (cluster of differentiation) were significantly higher in 12.7% PL group than those in 2.52% group (P<0.05). Compared to 2.53% PL group, the transcript levels of fatty acid synthase and stearoyl-CoA desaturase I were significantly lower in 6.32% PL group (P<0.05), while peroxisome proliferators-activated receptor alpha, carnitine palmitoyl transferase-I and acyl CoA oxidase mRNA expression levels were significantly higher in 12.7% PL group (P<0.05). These results indicated that dietary PL could enhance antioxidant capacity of larvae. Dietary PL might regulate lipid metabolism in large yellow croaker larvae by modulating fatty acids delivery, uptake, synthesis and oxidation at transcriptional level and improved fatty acids delivery and uptake might be responsible for higher body lipid content in 6.32% and 12.7% groups. PMID- 27354253 TI - Cold atmospheric plasma: a new tool for the treatment of superficial driveline infections. AB - Percutaneous driveline infections (DI) are leading factors for morbidity and mortality in ventricular assist device (VAD) patients. In recent years, cold atmospheric plasma (CAP) has been safely and effectively used in clinical settings to treat topical infections. We describe the first use of CAP to treat a superficial DI. CAP was applied with the kinPen(r) MED plasma jet device (neoplas tools GmbH, Greifswald, Germany), in the treatment of a DI in a 66-year-old VAD patient in Klinikum Karlsburg, Germany. The patient received a daily application of CAP of 1 min for 12 days. One CAP application was administered each week for 4 weeks in our outpatient clinic after patient discharge. Laboratory tests were conducted and photographs of the driveline exit site were taken. After CAP treatment, the local infection was completely regressed without any signs of exudation or recurrence of the infection. There were no adverse side effects observed, and the HVAD logfile data did not show any abnormalities during treatment. Here, we demonstrate a successful resolution of a VAD DI with the kinPen plasma jet device. We believe that CAP has the potential to be a simple and effective tool in the treatment of superficial DIs. PMID- 27354254 TI - Predictive ability of the CHADS2 and CHA2DS2-VASc scores for stroke after transcatheter aortic balloon-expandable valve implantation: an Italian Transcatheter Balloon-Expandable Valve Implantation Registry (ITER) sub-analysis. AB - OBJECTIVES: Stroke incidence after transcatheter aortic valve implantation (TAVI) still represents a concern. This multicentre study aimed at investigating the hypothesis that CHADS2 and CHA2DS2-VASc scores may be used to predict perioperative stroke after TAVI. METHODS: The Italian Transcatheter Balloon Expandable Valve Implantation Registry (ITER) is a multicentre, prospective registry of patients undergoing balloon-expandable TAVI using Edwards Sapien and Sapien XT prosthesis between 2007 and 2012. The primary end-point of this study was the 30-day stroke rate. Secondary safety end-points were all the major adverse events based on Valve Academic Research Consortium (VARC-2) criteria. RESULTS: One thousand nine hundred and four patients were enrolled in the registry. Mean age was 81.6 +/- 6.2 years and 1147 (60.2%) patients were female; mean CHADS2 and CHA2DS2-VASc scores were 2.2 +/- 0.8 and 4.4 +/- 1.1, respectively. Fifty-four (2.8%) patients had a stroke within 30 days. At multivariable logistic regression analysis, CHA2DS2-VASc (OR: 1.35, 95% CI: 1.03 1.78; P = 0.031) and previous cardiac surgery (OR: 1.96, 95% CI: 1.06-3.6; P = 0.033) but not CHADS2 (OR: 1.05, 95% CI: 0.76-1.44; P = 0.77) were found to be independent predictors of in-hospital stroke. A CHA2DS2-VASc score >=5 was strongly related to the occurrence of in-hospital stroke (OR: 2.51, 95% CI: 1.38 4.57; P= 0.001). However, CHA2DS2-VASc score showed only poor accuracy for in hospital stroke with a trend for better accuracy when compared with CHADS2 score (area under the curve: 0.61, 95% CI: 0.59-0.63 vs 0.51; 95% CI: 0.49-0.54, respectively, P = 0.092). CONCLUSIONS: In TAVI patients, CHA2DS2-VASc provided a strong correlation for in-hospital stroke but with low accuracy. Dedicated scores to properly tailor procedures and preventive strategies are needed. PMID- 27354255 TI - Ventricular volume and myocardial viability, evaluated using cardiac magnetic resonance imaging, affect long-term results after surgical ventricular reconstruction. AB - OBJECTIVES: We aimed to investigate the outcomes of surgical ventricular reconstruction (SVR) for ischaemic cardiomyopathy and to identify ideal candidates for this procedure using cardiac magnetic resonance imaging (MRI) studies. METHODS: We retrospectively examined 50 patients who underwent SVR and were preoperatively evaluated using cardiac MRI from 2004 to 2014. Cine MRI and gadolinium-enhanced MRI were performed to evaluate left ventricular (LV) volume and scarring. The midterm (median, 2.5 years) risk factors of cardiac death or major adverse cardiac events (MACEs) were analysed. Patients were divided into three groups-those with preoperative indexed LV end-systolic volume (LVESVI) of <=100 ml/m2 (Group 1), those with LVESVI of >100 and <=130 ml/m2 (Group 2) and those with LVESVI of >130 ml/m2 (Group 3)-and examined. RESULTS: In total, 17 patients exhibited MACEs at follow-up. Kaplan-Meier analysis showed that the 5 year rate of freedom from MACEs was 66%. The Cox hazard model indicated that preoperative LVESVI was the only significant predictor for MACEs (P = 0.006; hazard ratio, 1.02; 95% confidence interval, 1.01-1.04). Moreover, a significant reduction in LVESVI and an increase in LV ejection fraction (LVEF) were observed early after SVR (preoperative versus postoperative: LVESVI, 110 +/- 44 vs 68 +/- 28 ml/m2, P < 0.001; LVEF, 24.3 +/- 10.3 vs 32.0 +/- 10.4%, P < 0.001) and at follow-up (LVESVI, 61 +/- 28 ml/m2, P < 0.001; LVEF, 36.5 +/- 11.5%, P < 0.001). Although no difference was observed between the groups at follow-up, LVEF and LVESVI primarily improved in Group 2. LVEF improvement was significantly greater in Group 2 than in Group 1 (%increase in LVEF: Group 1, 6%; Group 2, 18%; P = 0.008). In patients with a preoperative LVESVI of >130 ml/m2, the number of non viable segments was a significant risk factor for MACEs. CONCLUSIONS: Patients with preoperative LVESVI ranging from 100 to 130 ml/m2 had fairly better outcomes, and the percentage improvement in LVEF and the percentage reduction in LVESVI were more pronounced in these patients. Hence, accurate preoperative assessments of LV volume and viability testing using cardiac MRI studies are essential for better stratification of the SVR procedure. PMID- 27354256 TI - Fungal native pulmonary valve endocarditis: facing both medical and surgical challenges. AB - Fungal isolated native pulmonary valve endocarditis is extremely uncommon. Data are scarce and report high mortality and recurrence rates. Recommended management combines both medical and surgical approaches. We report herein a rare case of isolated pulmonary valve endocarditis caused by Candida albicans The patient did not display prior heart disease. Medical management was unsuccessful. Pulmonary valve replacement allowed rapid improvement. PMID- 27354257 TI - Racemose haemangioma secondary to coronary artery fistula. PMID- 27354258 TI - A phase III clinical study to compare the immunogenicity and safety of the 9 valent and quadrivalent HPV vaccines in men. AB - BACKGROUND: A nine-valent human papilloma virus (9vHPV) vaccine has been developed to prevent infections and diseases related to HPV 6/11/16/18 (as per the licensed quadrivalent HPV (qHPV) vaccine) as well as to five additional oncogenic HPV types (HPV 31/33/45/52/58). The 9vHPV vaccine has the potential to prevent 90% of cervical cancers, HPV-related anal, vaginal and vulval cancers and anogenital warts. We compared the immunogenicity and safety of the 9vHPV vaccine versus the qHPV vaccine in 16-26-year-old men. METHODS: Participants (N=500) were randomised to receive 9vHPV or qHPV vaccines on day 1, month 2 and month 6. Serology testing was performed on day 1 and month 7. HPV type-specific antibody titres (anti-HPV 6/11/16/18/31/33/45/52/58) were determined by competitive Luminex immunoassay and expressed as geometric mean titres and seroconversion rates. Vaccine safety was also assessed. RESULTS: The HPV 6/11/16/18 immune responses elicited by the 9vHPV vaccine were comparable with those elicited by the qHPV vaccine. All participants receiving the 9vHPV vaccine seroconverted for HPV 31/33/45/52/58. The 9vHPV and qHPV vaccines showed comparable safety profiles. CONCLUSIONS: In addition to immune responses to HPV 31/33/45/52/58, a three-dose regimen of the 9vHPV vaccine elicited a similar immune response to HPV 6/11/16/18 when compared with the qHPV vaccine in men aged 16-26years. The safety profile was also similar for the two vaccines. The results from this study support extending the efficacy findings with qHPV vaccine to 9vHPV vaccine in men aged 16-26years. NCT02114385. PMID- 27354259 TI - Reaching the unreached with polio vaccine and other child survival interventions through partnership with military in Angola. AB - BACKGROUND: Growing conflict and insecurity played a major role in precipitating polio outbreaks in the Horn of Africa and the Middle East. In Angola, the early post-conflict situation was characterized by the presence of many inaccessible zones and districts due to insecurity and poor infrastructure. Partnership with the Angolan Army health service (AAHS) was one of the innovative strategies that the Polio Eradication Initiative (PEI) introduced into the country to support the polio vaccination campaigns in insecure and hard to reach zones. METHODS: Before embarking on creating a partnership with Angolan military it was essential to make high-level advocacy with top military decision makers to engage the leadership in the process for better and sustainable support to the strategy. The principal supports provided by the AAHS were the administration of oral polio vaccine, vitamin A, deworming agents, social mobilization, monitoring campaign quality, and surveillance. Distribution of logistics using military vehicles and helicopters to hard to reach and insecure zones was also part of the support. RESULTS: Using this partnership it was possible to reach a significant number of children in insecure and hard to reach areas with polio vaccine and other child survival interventions. The military partnership also contributed in increasing the demand and addressing rejection for the polio vaccine. CONCLUSION: Military is a potentially productive force that can be used for any development activities in any country. The Angolan experience has demonstrated that it is possible to form a partnership with the military for basic health intervention activities with little training and investment. PMID- 27354261 TI - Morphometric evaluation of the early stages of healing at cortical and marrow compartments at titanium implants: an experimental study in the dog. AB - OBJECTIVE: To study the early sequential stages of tissue composition in the cortical and marrow compartments of the alveolar bone crest at implants with a moderately rough surface. MATERIALS AND METHODS: Three month after tooth extraction in 12 Labrador dogs, full-thickness flaps were elevated in the edentulous region of the right side of the mandible and one implant was installed. The flaps were sutured to allow a fully submerged healing. The timing of the installations in the left side of the mandible and of sacrifices were scheduled in such a way to obtained biopsies representing the healing after 5, 10, 20, and 30 days. Ground sections (n = 6 per each healing period) were prepared, and the percentages of osteoid/new bone, old bone, new soft tissues (provisional matrix and primitive marrow), mature bone marrow, vessels, and other tissues (bone debris/particles and clot) were evaluated laterally to the implant surface up to a distance of about 0.4 mm from it. RESULTS: Osteoid/new bone was found after 5 days at percentages of 10.8 +/- 4.3% at the marrow and 0.6 +/- 0.6% at the cortical compartments. After 30 days, these percentages increased up to 56.4 +/- 4.0% and 23.3 +/- 6.1%, respectively. Old parent bone was resorbed between 5 and 30 days from 28.7 +/- 10.9% to 14.9 +/- 3.4% at the marrow (~48% of resorption) and from 81.2 +/- 9.4% to 67.6 +/- 5.6% at the cortical (~17% of resorption) compartments. All differences were statistically significant. CONCLUSION: Bone apposition to an implant surface followed a significantly different pattern in the compact and the marrow compartments around the implants. While in the compact compartments, bone apposition had to develop through the BMUs following resorption, it developed in very dense layers through an early apposition in the marrow compartments. PMID- 27354260 TI - Molecular characterization of woodchuck IFI16 and AIM2 and their expression in woodchucks infected with woodchuck hepatitis virus (WHV). AB - IFI16 and AIM2 are important DNA sensors in antiviral immunity. To characterize these two molecules in a woodchuck model, which is widely used to study hepatitis B virus (HBV) infection, we cloned and analyzed the complete coding sequences (CDSs) of woodchuck IFI16 and AIM2, and found that AIM2 was highly conserved in mammals, whereas the degree of sequence identity between woodchuck IFI16 and its mammalian orthologues was low. IFI16 and IFN-beta were upregulated following VACV ds 70 mer transfection, while AIM2 and IL-1beta were upregulated following poly (dA:dT) transfection, both in vitro and in vivo; IFI16-targeted siRNA decreased the transcription of IFI16 and IFN-beta stimulated by VACV ds 70 mer, and AIM2 siRNA interference downregulated AIM2 and IL-1beta transcripts stimulated by poly (dA:dT), in vitro, suggesting that woodchuck IFI16 and AIM2 may play pivotal roles in the DNA-mediated induction of IFN-beta and IL-1beta, respectively. IFI16 and AIM2 transcripts were upregulated in the liver and spleen following acute WHV infection, while IFI16 was downregulated in the liver following chronic infection, implying that IFI16 and AIM2 may be involved in WHV infection. These data provide the basis for the study of IFI16- and AIM2-mediated innate immunity using the woodchuck model. PMID- 27354262 TI - Deep sequencing and in silico analyses identify MYB-regulated gene networks and signaling pathways in pancreatic cancer. AB - We have recently demonstrated that the transcription factor MYB can modulate several cancer-associated phenotypes in pancreatic cancer. In order to understand the molecular basis of these MYB-associated changes, we conducted deep-sequencing of transcriptome of MYB-overexpressing and -silenced pancreatic cancer cells, followed by in silico pathway analysis. We identified significant modulation of 774 genes upon MYB-silencing (p < 0.05) that were assigned to 25 gene networks by in silico analysis. Further analyses placed genes in our RNA sequencing-generated dataset to several canonical signalling pathways, such as cell-cycle control, DNA damage and -repair responses, p53 and HIF1alpha. Importantly, we observed downregulation of the pancreatic adenocarcinoma signaling pathway in MYB-silenced pancreatic cancer cells exhibiting suppression of EGFR and NF-kappaB. Decreased expression of EGFR and RELA was validated by both qPCR and immunoblotting and they were both shown to be under direct transcriptional control of MYB. These observations were further confirmed in a converse approach wherein MYB was overexpressed ectopically in a MYB-null pancreatic cancer cell line. Our findings thus suggest that MYB potentially regulates growth and genomic stability of pancreatic cancer cells via targeting complex gene networks and signaling pathways. Further in-depth functional studies are warranted to fully understand MYB signaling in pancreatic cancer. PMID- 27354263 TI - Revised version of quality guidelines for presurgical epilepsy evaluation and surgical epilepsy therapy issued by the Austrian, German, and Swiss working group on presurgical epilepsy diagnosis and operative epilepsy treatment. AB - The definition of minimal standards remains pivotal as a basis for a high standard of care and as a basis for staff allocation or reimbursement. Only limited publications are available regarding the required staffing or methodologic expertise in epilepsy centers. The executive board of the working group (WG) on presurgical epilepsy diagnosis and operative epilepsy treatment published the first guidelines in 2000 for Austria, Germany, and Switzerland. In 2014, revised guidelines were published and the WG decided to publish an unaltered English translation in this report. Because epilepsy surgery is an elective procedure, quality standards are particularly high. As detailed in the first edition of these guidelines, quality control relates to seven different domains: (1) establishing centers with a sufficient number of sufficiently and specifically trained personnel, (2) minimum technical standards and equipment, (3) continuous medical education of employees, (4) surveillance by trained personnel during video electroencephalography (EEG) monitoring (VEM), (5) systematic acquisition of clinical and outcome data, (6) the minimum number of preoperative evaluations and epilepsy surgery procedures, and (7) the cooperation of epilepsy centers. These standards required the certification of the different professions involved and minimum numbers of procedures. In the subsequent decade, quite a number of colleagues were certified by the trinational WG; therefore, the executive board of the WG decided in 2013 to make these standards obligatory. This revised version is particularly relevant given that the German procedure classification explicitly refers to the guidelines of the WG with regard to noninvasive/invasive preoperative video-EEG monitoring and invasive intraoperative diagnostics in epilepsy. PMID- 27354264 TI - Internalized racism and mental health among African-Americans, US-born Caribbean Blacks, and foreign-born Caribbean Blacks. AB - OBJECTIVES: The tripartite model of racism includes personally mediated racism, institutionalized racism, and the less-oft studied internalized racism. Internalized racism - or negative beliefs about one's racial group - results from cultural racism that is endemic in American society. In this project, we studied whether these negative stereotypes are associated with mental health among African-Americans and Caribbean Blacks. DESIGN: Using secondary data from the National Survey of American Life, we investigated the association between internalized racism and mental health (measured by depressive symptoms and serious psychological distress (SPD)) among these two groups. We also explored whether ethnicity/nativity and mastery moderate the association between internalized racism and mental health among African-Americans and Caribbean Blacks. RESULTS: Internalized racism was positively associated with depressive symptoms and SPD among all Black subgroups. However, internalized racism was a weaker predictor of SPD among foreign-born Caribbean Blacks than US-born Caribbean Blacks and US-born African-Americans. Additionally, higher mastery was protective against distress associated with internalized racism. CONCLUSION: Internalized racism is an important yet understudied determinant of mental health among Blacks. Future studies should take into account additional heterogeneity within the Black population (e.g. African-born individuals) and other potential protective mechanisms in addition to mastery (e.g. self-esteem and racial identity). PMID- 27354265 TI - Miscoding of Melanoma Thickness in SEER: Research and Clinical Implications. AB - Melanoma-related deaths and metastases among patients with thin (<=1 mm) and ultrathin (<=0.25 mm) melanomas have been reported. These observations might reflect adverse biology and/or errors in administrative data. Cumulative melanoma related death rates for thickness groups of patients with thin melanomas were compared among five cohorts including the Surveillance, Epidemiology, and End Results (SEER) registry. Thickness in one SEER region was reexamined in pathology reports. The 5-year cumulative melanoma-related death rate of patients with ultrathin melanomas was higher in SEER (2.8%) compared with other registries (0.6 0.9%). The rates across the 16 SEER regions were 0.25% to 8.4%. In SEER, 21% of thin melanomas were ultrathin; in other registries, they comprised 5.8-15%. A reexamination of thickness in one SEER site revealed that 114 of 447 ultrathin melanomas had errors; after correction, only 17 of the 114 remained ultrathin. The majority of errors were related to decimal point placement. The 86 thin melanomas reclassified to >1.00 mm included 96% of the original ultrathin associated deaths and 100% of the original positive lymph nodes. Significant miscoding of thickness that is concentrated in ultrathin lesions is present in SEER and results in mischaracterization of patient outcomes. When using administrative data, validation of results can identify critical data issues. PMID- 27354266 TI - Screening disordered eating in a representative sample of the German population: Usefulness and psychometric properties of the German SCOFF questionnaire. AB - The prevention of eating disorders and the identification of high-risk individuals are essential for the public health sector. There is need for sensitive and specific screening instruments of disordered eating that can be applied in universal samples as an initial step into disease prevention. The SCOFF is a screening instrument for disordered eating, frequently used in international and cross-cultural contexts to detect individuals at risk. The objective of this research is to evaluate whether the SCOFF can be used as a screening tool for disordered eating in universal samples. This is the first study which examined the psychometric properties of the German version of the SCOFF in a general population sample. A representative sample (N=2527) of the German population, aged 14-95years, was recruited. Psychometric properties were determined including reliability, concurrent and construct validity, and factor structure. The prevalence of disordered eating was assessed. The prevalence of disordered eating in the general population was 10%. Using the established cutoff point of >=2, values for diagnostic accuracy were 26% (sensitivity), 97% (specificity), 80% (positive predictive value), and 74% (negative predictive value). Factorial analyses revealed an excellent model fit of a unidimensional model. Due to its low sensitivity and a high percentage of false negatives, there are limitations in using the German version of the SCOFF in general population samples with wide age ranges. PMID- 27354267 TI - ABCC4, ABCC5 and SLC28A1 polymorphisms: host genome on responses of chronic hepatitis B patients with entecavir treatment. AB - BACKGROUND: Nucleoside drug transporter polymorphisms play a significant role in patient responses to drugs. The aim was to investigate the effect of multi-drug resistance protein 4, multi-drug resistance protein 5 and human concentrative nucleoside transporter 1 gene polymorphisms on the response to entecavir treatment in chronic hepatitis B patients. METHODS: A total of 324 chronic HBV treatment-naive Chinese Han patients treated with entecavir 0.5 mg daily for 1 year were enrolled. Patients were divided into a response group and non-response group according to the decline of HBV DNA levels. A multiplex SNaPshot single base extension method was designed for genotyping. RESULTS: The rs3751333GG genotype of multi-drug resistance protein 4 was significantly different between the response group and non-response group at 6 and 12 months (P=0.005 and P=0.019, respectively). Multivariate analysis showed that the rs37751333GG genotype was significantly associated with responses at 6 and 12 months (odds ratio 2.630, 95% CI 1.391, 4.974, P=0.003; odds ratio 2.968, 95% CI 1.416, 6.221, P=0.004). CONCLUSIONS: The multi-drug resistance protein 4 variant was significantly associated with HBV DNA level suppression in chronic hepatitis B patients treated with entecavir, and therefore, patients with the rs3751333GG genotype might respond better to entecavir in the Chinese Han population. PMID- 27354268 TI - Dissection of the Major Hematopoietic Quantitative Trait Locus in Chromosome 6q23.3 Identifies miR-3662 as a Player in Hematopoiesis and Acute Myeloid Leukemia. AB - Chromosomal aberrations and multiple genome-wide association studies (GWAS) have established a major hematopoietic quantitative trait locus in chromosome 6q23.3. The locus comprises an active enhancer region, in which some of the associated SNPs alter transcription factor binding. We now identify miR-3662 as a new functional driver contributing to the associated phenotypes. The GWAS SNPs are strongly associated with higher miR-3662 expression. Genome editing of rs66650371, a three-base-pair deletion, suggests a functional link between the SNP genotype and the abundance of miR-3662. Increasing miR-3662's abundance increases colony formation in hematopoietic progenitor cells, particularly the erythroid lineage. In contrast, miR-3662 is not expressed in acute myeloid leukemia cells, and its overexpression has potent antileukemic effects in vitro and in vivo Mechanistically, miR-3662 directly targets NF-kappaB-mediated transcription. Thus, miR-3662 is a new player of the hematopoietic 6q23.3 locus. SIGNIFICANCE: The characterization of miR-3662 has identified a new actor in the prominent hematopoietic quantitative trait locus in chromosome 6q23.3. The mechanistic insights into miR-3662's function may reveal novel or only partially known pathways for normal and malignant hematopoietic cell proliferation. Cancer Discov; 6(9); 1036-51. (c)2016 AACR.This article is highlighted in the In This Issue feature, p. 932. PMID- 27354270 TI - Tumor Profiling: Adding Proteomics to Genomics. AB - Researchers have used mass spectrometry to conduct proteomic analyses of 77 genomically characterized breast tumors. Through this approach, they've uncovered functional consequences of somatic mutations. For instance, EGFR overexpression in basal-like breast cancer is potentially driven by the loss of two genes, SKP1 and CETN3, from the chromosome 5q deletion characteristic of this disease subtype. PMID- 27354271 TI - Single-Agent Abemaciclib Active in Breast Cancer. AB - According to results from a phase II study, abemaciclib shows single-agent activity in women with metastatic HER2-negative, ER-positive breast cancer whose disease has progressed on endocrine therapy and chemotherapy. The objective response rate to this investigational CDK4/6 inhibitor was 19.7%, with 28.2% of responses lasting at least a year. PMID- 27354269 TI - Triggering the TCR Developmental Checkpoint Activates a Therapeutically Targetable Tumor Suppressive Pathway in T-cell Leukemia. AB - Cancer onset and progression involves the accumulation of multiple oncogenic hits, which are thought to dominate or bypass the physiologic regulatory mechanisms in tissue development and homeostasis. We demonstrate in T-cell acute lymphoblastic leukemia (T-ALL) that, irrespective of the complex oncogenic abnormalities underlying tumor progression, experimentally induced, persistent T cell receptor (TCR) signaling has antileukemic properties and enforces a molecular program resembling thymic negative selection, a major developmental event in normal T-cell development. Using mouse models of T-ALL, we show that induction of TCR signaling by high-affinity self-peptide/MHC or treatment with monoclonal antibodies to the CD3epsilon chain (anti-CD3) causes massive leukemic cell death. Importantly, anti-CD3 treatment hampered leukemogenesis in mice transplanted with either mouse- or patient-derived T-ALLs. These data provide a strong rationale for targeted therapy based on anti-CD3 treatment of patients with TCR-expressing T-ALL and demonstrate that endogenous developmental checkpoint pathways are amenable to therapeutic intervention in cancer cells. SIGNIFICANCE: T-ALLs are aggressive malignant lymphoid proliferations of T-cell precursors characterized by high relapse rates and poor prognosis, calling for the search for novel therapeutic options. Here, we report that the lineage specific TCR/CD3 developmental checkpoint controlling cell death in normal T-cell progenitors remains switchable to induce massive tumor cell apoptosis in T-ALL and is amenable to preclinical therapeutic intervention. Cancer Discov; 6(9); 972 85. (c)2016 AACR.See related commentary by Lemonnier and Mak, p. 946This article is highlighted in the In This Issue feature, p. 932. PMID- 27354272 TI - Blocking PD-1 in Tumors with Faulty DNA Repair. AB - A phase II study shows that DNA mismatch repair deficiency can render tumors highly sensitive to the PD-1 inhibitor pembrolizumab. Patients with a range of solid tumors, including colorectal and endometrial cancers, with the deficiency responded well and durably to immune checkpoint blockade, with minimal toxicity. PMID- 27354273 TI - Cardiac MRI evaluation of myocardial disease. AB - Cardiovascular magnetic resonance (CMR) is a key imaging technique for cardiac phenotyping with a major clinical role. It can assess advanced aspects of cardiac structure and function, scar burden and other myocardial tissue characteristics but there is new information that can now be derived. This can fill many of the gaps in our knowledge with the potential to change thinking, disease classifications and definitions as well as patient care. Established techniques such as the late gadolinium enhancement technique are now embedded in clinical care. New techniques are coming through. Myocardial tissue characterisation techniques, particularly myocardial mapping can precisely measure tissue magnetisation-T1, T2, T2* and also the extracellular volume. These change in disease. Key biological pathways are now open for scrutiny including focal fibrosis (scar) and diffuse fibrosis, inflammation, metabolism and infiltration. Other new areas to engage in where major insights are growing include detailed assessments of myocardial mechanics and performance, spectroscopy and hyperpolarised CMR. In spite of the advances, challenges remain, particularly surrounding utilisation, technical development to improve accuracy, reproducibility and deliverability, and the role of multidisciplinary research to understand the detailed pathological basis of the MR signal changes. Collectively, these new developments are galvanising CMR uptake and having a major translational impact on healthcare globally and it is steadily becoming key imaging tool. PMID- 27354274 TI - Cross-sectional analysis of deprivation and ideal cardiovascular health in the Paris Prospective Study 3. AB - AIMS: We hypothesised that deprivation might represent a barrier to attain an ideal cardiovascular health (CVH) as defined by the American Heart Association (AHA). METHODS AND RESULTS: The baseline data of 8916 participants of the Paris Prospective Study 3, an observational cohort on novel markers for future cardiovascular disease, were used. The AHA 7-item tool includes four health behaviours (smoking, body weight, physical activity and optimal diet) and three biological measures (blood cholesterol, blood glucose and blood pressure). A validated 11-item score of individual material and psychosocial deprivation, the Evaluation de la Precarite et des Inegalites dans les Centres d'Examens de Sante Evaluation of Deprivation and Inequalities in Health Examination centres (EPICES) score was used. The mean age was 59.5 years (standard deviation 6.2), 61.2% were men and 9.98% had an ideal CVH. In sex-specific multivariable polytomous logistic regression, the odds ratio (OR) for ideal behavioural CVH progressively decreased with quartile of increasing deprivation, from 0.54 (95% CI 0.41 to 0.72) to 0.49 (0.37 to 0.65) in women and from 0.61 (0.50 to 0.76) to 0.57 (0.46 to 0.71) in men. Associations with ideal biological CVH were confined to the most deprived women (OR=0.60; 95% CI 0.37 to 0.99), whereas in men, greater deprivation was related to higher OR of intermediate biological CVH (OR=1.28; 95% CI 1.05 to 1.57 for the third quartile vs the first quartile). CONCLUSIONS: Higher material and psychosocial deprivation may represent a barrier to reach an ideal CVH. TRIAL REGISTRATION NUMBER: NCT00741728. PMID- 27354275 TI - Circulating vascular endothelial growth factor and the risk of cardiovascular events. AB - OBJECTIVE: To investigate the relation of circulating concentrations of vascular endothelial growth factor (VEGF) for the risk of developing cardiovascular disease (CVD) in a large community-based sample. METHODS: We prospectively assessed the relation of circulating VEGF concentrations with the incidence of CVD among 3041 Framingham Heart Study participants (mean age 63.4+/-11.1 years, 59% women). Multivariable Cox proportional hazards models were estimated adjusting for standard risk factors to VEGF quartiles to incident CVD. Restricted cubic splines were used to examine the linearity of the association. RESULTS: After a mean follow-up of 8.8 (+/-2.8) years, 527 individuals experienced a first CVD event. Compared with participants in the first VEGF quartile, individuals in the second VEGF quartile had a 34% increased risk for future CVD (HR 1.34, 95% CI 1.03 to 1.74; p value=0.03) and individuals in third quartile had a 59% higher risk (HR 1.59; 95% CI 1.23 to 2.05, p value=0.0003). Individuals in the highest VEGF quartile had a similar cardiovascular risk as compared with those in the lowest VEGF quartile (HR 1.18, 95% CI 0.91 to 1.53, p value=0.21). Evaluation of restricted cubic splines confirmed the nonlinear, inverted U-shaped relation of serum VEGF and CVD events (p<0.0001 for model fit, p=0.006 for non-linearity). CONCLUSIONS: Circulating VEGF concentrations exhibit a complex non-linear (inverted U-shaped) relation with the risk of developing CVD events, with the lowest risk experienced at the lower and upper end of the distribution. The underlying pathophysiological mechanisms remain to be elucidated. PMID- 27354276 TI - Patients with Down syndrome and congenital heart disease: survival is improving, but challenges remain. PMID- 27354277 TI - Maintaining good clinical practice: publication of outcomes and handling of outliers. PMID- 27354278 TI - The mediating role of perceived peer support in the relation between quality of attachment and internalizing problems in adolescence: a longitudinal perspective. AB - The study was aimed to verify, from a longitudinal perspective, whether perceived peer support would mediate the relationship between attachment and internalizing problems. Longitudinal participants included 482 adolescents (245 boys) aged 14 15 years in Wave 1 and 17-18 years in Wave 2. Participants in Wave 1 completed the Relationship Questionnaire, and those in Wave 2 completed the Social Support Questionnaire and the Youth Self-Report. Results showed that secure attachment positively predicted high levels of perceived peer support and negatively predicted internalizing problems, whereas fearful and preoccupied attachment negatively predicted perceived peer support and positively predicted internalizing problems. The mediation models showed that perceived peer support partially mediated the relationship between secure attachment and internalizing problems as well as between preoccupied attachment and internalizing problems and between fearful attachment and internalizing problems. Our results confirm the role of subjective perception of peer support in contributing to the prediction of internalizing problems beyond attachment styles. PMID- 27354279 TI - Phosphoryl Group Flow within the Pseudomonas aeruginosa Pil-Chp Chemosensory System: DIFFERENTIAL FUNCTION OF THE EIGHT PHOSPHOTRANSFERASE AND THREE RECEIVER DOMAINS. AB - Bacterial chemosensory signal transduction systems that regulate motility by type IV pili (T4P) can be markedly more complex than related flagellum-based chemotaxis systems. In T4P-based systems, the CheA kinase often contains numerous potential sites of phosphorylation, but the signaling mechanisms of these systems are unknown. In Pseudomonas aeruginosa, the Pil-Chp system regulates T4P-mediated twitching motility and cAMP levels, both of which play roles in pathogenesis. The Pil-Chp histidine kinase (ChpA) has eight "Xpt" domains; six are canonical histidine-containing phosphotransfer (Hpt) domains and two have a threonine (Tpt) or serine (Spt) in place of the histidine. Additionally, there are two stand alone receiver domains (PilG and PilH) and a ChpA C-terminal receiver domain (ChpArec). Here, we demonstrate that the ChpA Xpts are functionally divided into three categories as follows: (i) those phosphorylated with ATP (Hpt4-6); (ii) those reversibly phosphorylated by ChpArec (Hpt2-6), and (iii) those with no detectable phosphorylation (Hpt1, Spt, and Tpt). There was rapid phosphotransfer from Hpt2-6 to ChpArec and from Hpt3 to PilH, whereas transfer to PilG was slower. ChpArec also had a rapid rate of autodephosphorylation. The biochemical results together with in vivo cAMP and twitching phenotypes of key ChpA phosphorylation site point mutants supported a scheme whereby ChpArec functions both as a phosphate sink and a phosphotransfer element linking Hpt4-6 to Hpt2-3. Hpt2 and Hpt3 are likely the dominant sources of phosphoryl groups for PilG and PilH, respectively. The data are synthesized in a signaling circuit that contains fundamental features of two-component phosphorelays. PMID- 27354280 TI - Gingipains of Porphyromonas gingivalis Affect the Stability and Function of Serine Protease Inhibitor of Kazal-type 6 (SPINK6), a Tissue Inhibitor of Human Kallikreins. AB - Periodontitis, a chronic inflammation driven by dysbiotic subgingival bacterial flora, is linked on clinical levels to the development of a number of systemic diseases and to the development of oral and gastric tract tumors. A key pathogen, Porphyromonas gingivalis, secretes gingipains, cysteine proteases implicated as the main factors in the development of periodontitis. Here we hypothesize that gingipains may be linked to systemic pathologies through the deregulation of kallikrein-like proteinase (KLK) family members. KLKs are implicated in cancer development and are clinically utilized as tumor progression markers. In tissues, KLK activity is strictly controlled by a limited number of tissue-specific inhibitors, including SPINK6, an inhibitor of these proteases in skin and oral epithelium. Here we identify gingipains as the only P. gingivalis proteases responsible for SPINK6 degradation. We further show that gingipains, even at low nanomolar concentrations, cleaved SPINK6 in concentration- and time-dependent manner. The proteolysis was accompanied by loss of inhibition against KLK13. We also mapped the cleavage by Arg-specific gingipains to the reactive site loop of the SPINK6 inhibitor. Moreover, we identified a significant fraction of SPINK6 sensitive proteases in healthy saliva and confirmed the ability of gingipains to inactivate SPINK6 under ex vivo conditions. Finally, we demonstrate the double edge action of gingipains, which, in addition, can activate KLKs because of gingipain K-mediated proteolytic processing of the zymogenic proform of KLK13. Altogether, the results indicate the potential of P. gingivalis to disrupt the control system of KLKs, providing a possible mechanistic link between periodontal disease and tumor development. PMID- 27354281 TI - Lysosomal Acid Lipase Hydrolyzes Retinyl Ester and Affects Retinoid Turnover. AB - Lysosomal acid lipase (LAL) is essential for the clearance of endocytosed cholesteryl ester and triglyceride-rich chylomicron remnants. Humans and mice with defective or absent LAL activity accumulate large amounts of cholesteryl esters and triglycerides in multiple tissues. Although chylomicrons also contain retinyl esters (REs), a role of LAL in the clearance of endocytosed REs has not been reported. In this study, we found that murine LAL exhibits RE hydrolase activity. Pharmacological inhibition of LAL in the human hepatocyte cell line HepG2, incubated with chylomicrons, led to increased accumulation of REs in endosomal/lysosomal fractions. Furthermore, pharmacological inhibition or genetic ablation of LAL in murine liver largely reduced in vitro acid RE hydrolase activity. Interestingly, LAL-deficient mice exhibited increased RE content in the duodenum and jejunum but decreased RE content in the liver. Furthermore, LAL deficient mice challenged with RE gavage exhibited largely reduced post-prandial circulating RE content, indicating that LAL is required for efficient nutritional vitamin A availability. In summary, our results indicate that LAL is the major acid RE hydrolase and required for functional retinoid homeostasis. PMID- 27354282 TI - SLX4-SLX1 Protein-independent Down-regulation of MUS81-EME1 Protein by HIV-1 Viral Protein R (Vpr). AB - Evolutionarily conserved structure-selective endonuclease MUS81 forms a complex with EME1 and further associates with another endonuclease SLX4-SLX1 to form a four-subunit complex of MUS81-EME1-SLX4-SLX1, coordinating distinctive biochemical activities of both endonucleases in DNA repair. Viral protein R (Vpr), a highly conserved accessory protein in primate lentiviruses, was previously reported to bind SLX4 to mediate down-regulation of MUS81. However, the detailed mechanism underlying MUS81 down-regulation is unclear. Here, we report that HIV-1 Vpr down-regulates both MUS81 and its cofactor EME1 by hijacking the host CRL4-DCAF1 E3 ubiquitin ligase. Multiple Vpr variants, from HIV-1 and SIV, down-regulate both MUS81 and EME1. Furthermore, a C-terminally truncated Vpr mutant and point mutants R80A and Q65R, all of which lack G2 arrest activity, are able to down-regulate MUS81-EME1, suggesting that Vpr-induced G2 arrest is not correlated with MUS81-EME1 down-regulation. We also show that neither the interaction of MUS81-EME1 with Vpr nor their down-regulation is dependent on SLX4-SLX1. Together, these data provide new insight on a conserved function of Vpr in a host endonuclease down-regulation. PMID- 27354283 TI - Design and Characterization of Erwinia Chrysanthemi l-Asparaginase Variants with Diminished l-Glutaminase Activity. AB - Current FDA-approved l-asparaginases also possess significant l-glutaminase activity, which correlates with many of the toxic side effects of these drugs. Therefore, l-asparaginases with reduced l-glutaminase activity are predicted to be safer. We exploited our recently described structures of the Erwinia chrysanthemi l-asparaginase (ErA) to inform the design of mutants with diminished ability to hydrolyze l-glutamine. Structural analysis of these variants provides insight into the molecular basis for the increased l-asparagine specificity. A primary role is attributed to the E63Q mutation that acts to hinder the correct positioning of l-glutamine but not l-asparagine. The substitution of Ser-254 with either an asparagine or a glutamine increases the l-asparagine specificity but only when combined with the E63Q mutation. The A31I mutation reduces the substrate Km value; this is a key property to allow the required therapeutic l asparagine depletion. Significantly, an ultra-low l-glutaminase ErA variant maintained its cell killing ability. By diminishing the l-glutaminase activity of these highly active l-asparaginases, our engineered ErA variants hold promise as l-asparaginases with fewer side effects. PMID- 27354284 TI - Non-Classical Congenital Adrenal Hyperplasia in Childhood. AB - Congenital adrenal hyperplasia (CAH) is classified as classical CAH and non classical CAH (NCCAH). In the classical type, the most severe form comprises both salt-wasting and simple virilizing forms. In the non-classical form, diagnosis can be more confusing because the patient may remain asymptomatic or the condition may be associated with signs of androgen excess in the postnatal period or in the later stages of life. This review paper will include information on clinical findings, symptoms, diagnostic approaches, and treatment modules of NCCAH. PMID- 27354286 TI - Determinants of Breast and Cervical Cancer Screening Uptake Among Women in Turkey. AB - The aim of the study was to assess the influence of sociodemographic characteristics on breast and cervical cancer screening among women 30 years and older in Turkey. We used data from the National Chronic Diseases and Risk Factors Survey conducted by the Ministry of Health in 2011. Multivariate logistic regression analysis was used to assess the association of sociodemographic factors, lifestyle variables, and cancer screening. Overall, 22.0% of women ever had a Pap smear test for cervical cancer screening and 19.0% ever had a mammography for breast cancer screening(n = 6846). Individuals with a university degree, social security, doing moderate physical activity, and consuming 5 portions of fruit or vegetable/day were more likely to receive Pap smear test and mammography. Residing in the eastern region and living in rural area was associated with lower likelihood of receiving both types of screening. PMID- 27354285 TI - Elevated Angiopoietin-2 Level in Patients With Continuous-Flow Left Ventricular Assist Devices Leads to Altered Angiogenesis and Is Associated With Higher Nonsurgical Bleeding. AB - BACKGROUND: Nonsurgical bleeding is the most common adverse event in patients with continuous-flow left ventricular assist devices (LVADs) and is caused by arteriovenous malformations. We hypothesized that deregulation of an angiogenic factor, angiopoietin-2 (Ang-2), in patients with LVADs leads to increased angiogenesis and higher nonsurgical bleeding. METHODS: Ang-2 and thrombin levels were measured by ELISA and Western blotting, respectively, in blood samples from 101 patients with heart failure, LVAD, or orthotopic heart transplantation. Ang-2 expression in endothelial biopsy was quantified by immunofluorescence. Angiogenesis was determined by in vitro tube formation from serum from each patient with or without Ang-2-blocking antibody. Ang-2 gene expression was measured by reverse transcription-polymerase chain reaction in endothelial cells incubated with plasma from each patient with or without the thrombin receptor blocker vorapaxar. RESULTS: Compared with patients with heart failure or those with orthotopic heart transplantation, serum levels and endothelial expression of Ang-2 were higher in LVAD patients (P=0.001 and P<0.001, respectively). This corresponded to an increased angiogenic potential of serum from patients with LVADs (P<0.001), which was normalized with Ang-2 blockade. Furthermore, plasma from LVAD patients contained higher amounts of thrombin (P=0.003), which was associated with activation of the contact coagulation system. Plasma from LVAD patients induced more Ang-2 gene expression in endothelial cells (P<0.001), which was reduced with thrombin receptor blockade (P=0.013). LVAD patients with Ang-2 levels above the mean (12.32 ng/mL) had more nonsurgical bleeding events compared with patients with Ang-2 levels below the mean (P=0.003). CONCLUSIONS: Our findings indicate that thrombin-induced Ang-2 expression in LVAD patients leads to increased angiogenesis in vitro and may be associated with higher nonsurgical bleeding events. Ang-2 therefore may contribute to arteriovenous malformation formation and subsequent bleeding in LVAD patients. PMID- 27354287 TI - Network Modeling Identifies Patient-specific Pathways in Glioblastoma. AB - Glioblastoma is the most aggressive type of malignant human brain tumor. Molecular profiling experiments have revealed that these tumors are extremely heterogeneous. This heterogeneity is one of the principal challenges for developing targeted therapies. We hypothesize that despite the diverse molecular profiles, it might still be possible to identify common signaling changes that could be targeted in some or all tumors. Using a network modeling approach, we reconstruct the altered signaling pathways from tumor-specific phosphoproteomic data and known protein-protein interactions. We then develop a network-based strategy for identifying tumor specific proteins and pathways that were predicted by the models but not directly observed in the experiments. Among these hidden targets, we show that the ERK activator kinase1 (MEK1) displays increased phosphorylation in all tumors. By contrast, protein numb homolog (NUMB) is present only in the subset of the tumors that are the most invasive. Additionally, increased S100A4 is associated with only one of the tumors. Overall, our results demonstrate that despite the heterogeneity of the proteomic data, network models can identify common or tumor specific pathway-level changes. These results represent an important proof of principle that can improve the target selection process for tumor specific treatments. PMID- 27354288 TI - Hyaluronan Upregulates Mitochondrial Biogenesis and Reduces Adenoside Triphosphate Production for Efficient Mitochondrial Function in Slow Proliferating Human Mesenchymal Stem Cells. AB - Hyaluronan-coated surfaces preserve the proliferation and differentiation potential of mesenchymal stem cells by prolonging their G1-phase transit, which maintains cells in a slow-proliferative mode. Mitochondria are known to play a crucial role in stem cell self-renewal and differentiation. In this study, for the first time, the metabolic mechanism underlying the hyaluronan-regulated slow proliferative maintenance of stem cells was investigated by evaluating mitochondrial functions. Human placenta-derived mesenchymal stem cells (PDMSCs) cultured on hyaluronan-coated surfaces at 0.5, 3.0, 5.0, and 30 ug/cm2 were found to have an average 58% higher mitochondrial mass and an increase in mitochondrial DNA copy number compared to noncoated tissue culture surfaces (control), as well as a threefold increase in the gene expression of the mitochondrial biogenesis related gene PGC-1alpha. Increase in mitochondrial biogenesis led to a hyaluronan dose-dependent increase in mitochondrial membrane potential, ATP content, and oxygen consumption rate, with reactive oxygen species levels shown to be at least three times lower compared to the control. Although hyaluronan seemed to favor mitochondrial function, cell entry into a hyaluronan-regulated slow-proliferative mode led to a fivefold reduction in ATP production and coupling efficiency levels. Together, these results suggest that hyaluronan-coated surfaces influence the metabolic proliferative state of stem cells by upregulating mitochondrial biogenesis and function with controlled ATP production. This more efficiently meets the energy requirements of slow-proliferating PDMSCs. A clear understanding of the metabolic mechanism induced by hyaluronan in stem cells will allow future applications that may overcome the current limitations faced in stem cell culture. Stem Cells 2016;34:2512-2524. PMID- 27354289 TI - False-negative direct immunofluorescence testing in vancomycin-induced linear IgA bullous dermatosis: a diagnostic pitfall. PMID- 27354290 TI - Words will never hurt me? Preferred terms for describing obesity and binge eating. AB - OBJECTIVE: This study evaluated individuals' language preferences for discussing obesity and binge eating. METHOD: Participants (N = 817; 68.3% female) were an online community sample. They rated the desirability of terms related to obesity and binge eating, and also completed psychometrically established eating-disorder measures. In addition to examining participants' preferences, analyses explored whether preferences differed by socio-demographic variables, weight status and binge-eating status. RESULTS: Preferred obesity-related terms were weight and BMI, although women rated undesirable obesity-related terms even lower than did men. Participants with obesity and binge eating rated weight, BMI, unhealthy BMI and large size as less desirable than participants with obesity but not binge eating. Binge-related terms were generally ranked neutrally; preferred descriptions were kept eating even though not physically hungry and loss of control. CONCLUSIONS: Preferred terms were generally consistent across sex, weight status and binge-eating status. Using terms ranked more preferably and avoiding terms ranked more undesirably may enhance clinical interactions, particularly when discussing obesity with women and individuals reporting binge eating, as these groups had stronger aversion to some non-preferred terms. Findings that the selected binge-related descriptions were rated neutrally on average provide support for their use by clinicians. PMID- 27354291 TI - Wooden Foreign Body in the Skull Base: How Did We Miss It? AB - BACKGROUND: Timely detection of intraorbital and skull base wooden foreign bodies is crucial. Wooden foreign bodies are difficult to detect on imaging. The radiologist may fail to identify wooden foreign bodies on two thirds of initial scans and can miss them in almost one third of total cases. CASE DESCRIPTION: A 66-year-old woman sustained a penetrating injury through the left upper eyelid with a small tree branch. The branch was immediately removed in the field, and she was provided with prompt medical care at a local hospital. Initial computed tomography (CT) scan diagnosis was "posttraumatic sinusitis," and this was treated empirically with vancomycin and piperacillin/tazobactam. On the eighth day after injury, she developed progressive swelling and pain of her eyelid with left trigeminal/supraorbital numbness and complete left ophthalmoplegia. A new CT scan showed an open "track" from the region of the left upper orbit/superior rectus to the contralateral sphenoid sinus, which raised suspicion for a retained foreign body. Further imaging confirmed the suspicion. Endoscopic sinus surgery was performed with extraction of the wooden object and evacuation of the left orbital infection. CONCLUSIONS: This case indicates that intraorbital and skull base wooden foreign bodies are elusive, demanding a high index of suspicion from both clinicians and radiologists to identify retained material in the setting of ocular or sinus trauma. For better identification of wooden foreign bodies, bone windows on CT should have a width of -1000 Hounsfield units with a soft tissue window level of -500 Hounsfield units. PMID- 27354292 TI - (18)F-DOPA Positron Emission Tomography in Medulloblastoma: 2 Case Reports. AB - BACKGROUND: Medulloblastoma (MDB) is an aggressive embryonal brain tumor, with underlying altered genetics and biological pathways that account for very heterogeneous natural histories and clinical behaviors. Positron emission tomography (PET) using radiolabeled amino acids provides important metabolic information for the diagnosis of cerebral glioma but only a few data are available on amino acid PET in MDB. In particular, no cases of MDB imaging with 6 [(18)F]-fluoro-L-3,4-dihydroxyphenylalanine (F-DOPA) have previously been described. CASE DESCRIPTION: Two patients with different histologic subtypes of MDB were referred for F-DOPA PET to define the extent and metabolic degree of their diseases. The patients had a newly diagnosed large-cell/anaplastic MDB and a fourth relapse of classic MDB, respectively. F-DOPA PET was unremarkable in the first case; F-DOPA uptake was low in the second patient with the tumor/background ratio as high as 1.29. Comparison was made with magnetic resonance imaging, which showed fluid-attenuated inversion recovery positive diseases. Aggressive tumor growth was shown in the clinical course of both patients. CONCLUSIONS: The 2 cases reported here suggest that sensitivity of F-DOPA PET in MDB can be low. However, more comprehensive data are needed to conclude on the overall accuracy of F-DOPA PET in MDB. PMID- 27354293 TI - Rapid Time to Positivity of Cerebrospinal Fluid Culture with Coagulase-Negative Staphylococcus Is More Likely to Reflect a True Infection Than Contamination. AB - OBJECTIVE: Cerebrospinal fluid (CSF) culture is the gold standard for diagnosing postoperative central nervous system infection. The time to positivity (TTP) of an automated continuous blood culture system may indicate the original concentration of the organism. Coagulase-negative Staphylococcus (CoNS), the common organism recovered in CSF, poses difficulty in differentiating infection from contamination. This study investigated the TTP of CSF culture with CoNS and its relationship to clinical parameters and prognosis. METHODS: Adult neurosurgical patients with CoNS who recovered via the use of CSF culture in BacT/ALERT Pediatric FAN blood culture bottles and were admitted from September 2013 to July 2015 were enrolled. The demographics, clinical and microbiological data, and treatment were reviewed, and the TTP of each culture was retrieved. RESULTS: Thirty-nine adult patients with CoNS recovered from CSF culture were included. The TTP ranged from 7.68 to 57.36 hours. A univariate logistic regression analysis indicated patients with rapid TTP (<21.5 hours) compared with those with longer TTP were more likely to be female, show an effective response to antibiotic therapy within 7 days, have clean-contaminated surgical incisions, and show CSF leak. A multivariate logistic regression analysis indicated that being female, an effective antibiotic therapy within 7 days, and clean contaminated surgical incisions were independent predictors of rapid TTP. CONCLUSIONS: Targeted antibiotic therapy was more likely to be beneficial to patients with a rapid TTP within 7 days, which suggested that CoNS with a rapid TTP represents the pathogen of central nervous system infection rather than contamination in neurosurgical patients. PMID- 27354294 TI - Sphingosine 1-phosphate signaling impacts lymphocyte migration, inflammation and infection. AB - Sphingosine 1-phosphate (S1P) is a sphingosine containing lipid intermediate obtained from ceramide. S1P is known to be an important signaling molecule and plays multiple roles in the context of immunity. This lysophospholipid binds and activates G-protein-coupled receptors (GPCRs) known as S1P receptors 1-5 (S1P1 5). Once activated, these GPCRs mediate signaling that can lead to alterations in cell proliferation, survival or migration, and can also have other effects such as promoting angiogenesis. In this review, we will present evidence demonstrating a role for S1P in lymphocyte migration, inflammation and infection, as well as in cancer. The therapeutic potential of targeting S1P receptors, kinases and lyase will also be discussed. PMID- 27354295 TI - Protein-based profiling of the immune response to uropathogenic Escherichia coli in adult patients immediately following hospital admission for acute cystitis. AB - Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are common infections in humans. Despite the substantial healthcare cost represented by these infections, the human immune response associated with the infection immediately following the onset of symptoms in patients remains largely undefined. We performed a prospective study aimed at defining the milieu of urinary cytokines in adult inpatients in the 24-48 h period immediately following hospital admission for acute cystitis due to UPEC. Urine samples, analyzed using 27-target multiplex protein assays, were used to generate immune profiles for patients and compared to age- and gender-matched healthy controls. The levels of multiple pro-inflammatory cytokines were significantly elevated in urine as a result of infection, an observation consistent with prior findings in murine models and clinical literature. We also identified significant responses for several novel factors not previously associated with the human response to UTI, including Interleukin (IL)-4, IL-7, IL-9, IL-17A, eotaxin, Granulocyte-macrophage colony-stimulating factor (GM-CSF) and several growth factors. These data establish crucial parallels between the human immune response to UPEC and murine model UTI studies, and emphasize the complex but poorly defined nature of the human immune response to UPEC, particularly in the immediate period following the onset of symptoms for acute cystitis. PMID- 27354297 TI - Attitude as a Mediator between Acculturation and Behavioral Intention. AB - OBJECTIVE: Immigrants, specifically African-born black persons, are affected by the HIV epidemic in the U.S. The low level of condom use among immigrants is a risk factor for contracting HIV and STIs. Immigrants go through acculturation process in their new adopted countries-a process reported to influence many health risks and protective factors; however, the mechanism through which acculturation influences health behaviors is not well understood. Thus, study examined the mediating role of attitude in the relationship between acculturation and the intention to use male condoms in steady heterosexual relationships among Somali and Ethiopian immigrants in Minnesota. DESIGN AND SAMPLE: The study was a regression analysis and the method of data collection cross-sectional. Participants were (n = 205) Somali and Ethiopian immigrants in Minnesota who volunteered for the study. MEASURES: Study participants responded to questions on attitudes, behavioral intention, and acculturation levels. RESULTS: The indirect effect of acculturation through the mediator, attitude, was not significant, product coefficient (a * b) = 0.04, 95% CI: [0.00, 0.11]; hence attitude did not mediate the relationship between acculturation and the intention to use condoms in the study population. However, there were significant direct and total effects of acculturation (c' = .27, p < .05; c = .31, p < .05), respectively, on intention to use condoms. CONCLUSION: Results of the study may suggest that public health intervention strategies targeting condom use among immigrants should incorporate programs that improve English language training tailored to the cultural practices and values of the immigrants, and consider the effect of acculturation on condom use. PMID- 27354298 TI - DIAGNOSIS OF ENDOCRINE DISEASE: Prevalence of hypercortisolism in type 2 diabetes patients: a systematic review and meta-analysis. AB - OBJECTIVE: Type 2 diabetes (T2D) and Cushing's syndrome (CS) share clinical characteristics, and several small studies have recorded a high prevalence of hypercortisolism in T2D, which could have therapeutic implications. We aimed to assess the prevalence of endogenous hypercortisolism in T2D patients. DESIGN: Systematic review and meta-analysis of the literature. METHODS: A search was performed in SCOPUS, MEDLINE, and EMBASE for original articles assessing the prevalence of endogenous hypercortisolism and CS in T2D. Data were pooled in a random-effect logistic regression model and reported with 95% confidence intervals (95% CI). RESULTS: Fourteen articles were included, with a total of 2827 T2D patients. The pooled prevalence of hypercortisolism and CS was 3.4% (95% CI: 1.5-5.9) and 1.4% (95 CI: 0.4-2.9) respectively. The prevalence did not differ between studies of unselected patients and patients selected based on the presence of metabolic features such as obesity or poor glycemic control (P = 0.41 from meta-regression). Imaging in patients with hypercortisolism (n = 102) revealed adrenal tumors and pituitary tumors in 52 and 14% respectively. CONCLUSIONS: Endogenous hypercortisolism is a relatively frequent finding in T2D, which may have therapeutic implications. PMID- 27354299 TI - Targeting leiomyomas with all-trans-retinoic acid at phosphoinositide 3-kinase pathway suppression: Effective roles of beta-catenin and of signaling interactions. AB - AIM: Leiomyomas, monoclonal tumors developed by the transformation of myometrium somatic stem cells, are a major health concern that can severely impair quality of life. Pathological alterations of signaling pathways have been recognized as a key feature in a variety of human diseases. Our objective was to analyze treatment with all-trans-retinoic acid (ATRA) by suppression of the phosphoinositide 3-kinase (PI3K) pathway on growth, signaling pattern and interactions among PI3K/B-cell lymphoma 2 (Bcl2)/retinol leiomyoma proteins. METHODS: Cultures of paired myometrium and leiomyoma cells from premenopausal women undergoing hysterectomy were collected. Western blot and analysis of variance were used for analysis. RESULTS: Significant differences were detected between treatment with ATRA alone or with LY294002 (a PI3K growth suppressor) in response to treatment and among cell samples and cell numbers. Leiomyoma cells were less affected. Immunochemical analysis of signaling patterns demonstrated that treatments affected most of the examined protein levels differently. Significant differences between the cell type responses to treatment in pyruvate phosphate dikinase 1 (pPDK1), Bad and pbeta-catenin levels were identified. The pbeta-catenin level showed highly significant interaction between response to treatment and cell type. CONCLUSIONS: ATRA treatment on PI3K pathway suppression significantly affected growth, signaling pattern and interactions among PI3K/Bcl2/retinol proteins involved in the growth, survival and apoptosis of leiomyomas. Interpretation of our results suggests that increasing knowledge of the role of signaling interplay in the pathogenesis of leiomyomas may present an opportunity to use specific signal transduction inhibitors for treating and preventing this disorder. PMID- 27354296 TI - Neutrophil-generated oxidative stress and protein damage in Staphylococcus aureus. AB - Staphylococcus aureus is a ubiquitous, versatile and dangerous pathogen. It colonizes over 30% of the human population, and is one of the leading causes of death by an infectious agent. During S. aureus colonization and invasion, leukocytes are recruited to the site of infection. To combat S. aureus, leukocytes generate an arsenal of reactive species including superoxide, hydrogen peroxide, nitric oxide and hypohalous acids that modify and inactivate cellular macromolecules, resulting in growth defects or death. When S. aureus colonization cannot be cleared by the immune system, antibiotic treatment is necessary and can be effective. Yet, this organism quickly gains resistance to each new antibiotic it encounters. Therefore, it is in the interest of human health to acquire a deeper understanding of how S. aureus evades killing by the immune system. Advances in this field will have implications for the design of future S. aureus treatments that complement and assist the host immune response. In that regard, this review focuses on how S. aureus avoids host-generated oxidative stress, and discusses the mechanisms used by S. aureus to survive oxidative damage including antioxidants, direct repair of damaged proteins, sensing oxidant stress and transcriptional changes. This review will elucidate areas for studies to identify and validate future antimicrobial targets. PMID- 27354300 TI - Optimization of indirect pressure in order to temporize life-threatening haemorrhage: A simulation study. AB - BACKGROUND: Minimizing haemorrhage using direct pressure is intuitive and widely taught. In contrast, this study examines the use of indirect-pressure, specifically external aortic compression (EAC). Indirect pressure has great potential for temporizing bleeds not amenable to direct tamponade i.e. abdominal pelvic, junctional, and multi-site trauma. However, it is currently unclear how to optimize this technique. METHODS: We designed a model of central vessel compression using the Malbrain intra-abdominal pressure monitor and digital weigh scale. Forty participants performed simulated external aortic compression on the ground, on a stretcher mattress, and with and without a backboard. RESULTS: The greater the rescuer's bodyweight the greater was their mean compression (Pearson's correlation 0.93). Using one-hand, a mean of 28% participant bodyweight (95% CI, 26-30%) could be transmitted at sustainable effort, waist height, and on a stretcher. A second compressing hand increased the percentage of rescuer bodyweight transmission 10-22% regardless of other factors (i.e. presence/absence or a backboard; rescuer position) (p<0.001). Adding a backboard increased transmission of rescuer bodyweight 7-15% (p<0.001). Lowering the patient from waist-height backboard to the floor increased transmission of rescuer bodyweight 4-9% (p<0.001). Kneeling on the model was the most efficient method and transmitted 11% more weight compared to two-handed maximal compression (p<0.001). CONCLUSIONS: Efficacy is maximized with larger-weight rescuers who use both hands, position themselves atop victims, and compress on hard surfaces/backboards. Knee compression is most effective and least fatiguing, thus assisting rescuers of lower weight and lesser strength, where no hard surfaces exist (i.e. no available backboard or trauma on soft ground), or when lengthy compression is required (i.e. remote locations). Our work quantifies methods to optimize indirect pressure as a temporizing measure following life-threatening haemorrhage not amenable to direct compression, and while expediting compression devices or definitive treatment. PMID- 27354301 TI - Treating patella fractures with a fixed-angle patella plate-A prospective observational study. AB - INTRODUCTION: Anterior tension wiring using Kirschner wires (K-wires) is still considered the standard treatment for patella fractures, despite its high complication rate. The objective of this prospective clinical study was to evaluate intra- and perioperative complications as well as the clinical outcome of patients with patella fracture treated with a new developed bilateral, polyaxial, fixed-angle 2.7mm patella plate. PATIENTS AND METHODS: Between 2011 and 2014 all patients with a patella fracture were included in this prospective study and treated with a fixed-angle patella plate. Avulsion fractures of the inferior or superior pole of the patella were excluded. All fractures were classified according to the AO/OTA fracture classification. During a twelve-month follow up period all intra- and postoperative complications were recorded as well as the time until fracture healing. One year postoperatively the Lysholm Score, the pre- and postoperative Tegner Score, the Hospital for Special Surgery Knee Score (HSS), the Turba Score, the Oxford Knee Score, the Knee injury and Osteoarthritis Outcome Score (KOOS), the Bostman Score and the Iowa Knee Score were surveyed. Altogether, 20 patella fractures in 19 patients were included in this prospective study. The most frequent type of fracture, n=10, was a simple transverse patella fracture (C1), followed by 7 comminuted patella fractures (C3) and 3 T-shaped patella fractures (C2). RESULTS: During the 12-month follow up period two patients treated with the patella plate had a complication. In one patient a superficial wound infection occurred, which was treated successfully with hardware removal and in one patient a fracture dislocation due to an implant failure occurred. X-rays demonstrated complete bony healing in all fractures on average 3.2 months postoperatively. All knee scores showed good to excellent clinical results one year postoperatively. CONCLUSION: The results of this first clinical study indicate that the fixed-angle patella plate is an effective and safe treatment option for patella fractures with a short operative learning curve. The treatment of communited patella fractures (C3) with a fixed-angle patella plate should be well-considered to avoid distending the indication and biomechanical properties. PMID- 27354302 TI - Colorectal cancer resection in the Australian nonagenarian patient. AB - AIM: The nonagenarian population is a rapidly growing segment of the Australian population. Surgical resection continues to offer the best chance of long-term survival in colorectal cancer. The primary aims of the present study were to evaluate the 30-day mortality and survival of Australian patients >= 90 years of age undergoing surgical resection for colorectal cancer in our health service. The secondary aims were to examine the clinicopathological characteristics of the patients and their tumours. METHOD: All patients >= 90 years of age undergoing surgical resection for colorectal cancer from 1998 to 2012 were identified in a centralized multihospital database. Key clinicopathological data, 30-day mortality and long-term overall survival were recorded for each patient. RESULTS: There were 121 patients identified of median age 91 years, 74% of whom were female. The median tumour size was 40 mm, and 51% of operations were carried out as an emergency. The TNM stage was Stage I/II in 57%, Stage III in 40% and Stage IV in 3%. The 30-day mortality was 6.6% (eight of 121) and the 1-, 3- and 5-year overall survival rates were 82.6%, 50.2% and 32.3%, respectively. CONCLUSION: Surgical resection in the nonagenarian patient has an acceptable mortality and offers good overall survival. PMID- 27354303 TI - Pathogenicity and genetic characterization of a duck Tembusu virus associated with egg-dropping in Muscovy ducks. AB - Duck Tembusu virus (DTMUV) has spread to the major duck-farming region in China, causing acute egg-production drop in Chinese duck population. In this study, we characterized a DTMUV strain (named GD2014) isolated from an egg-production drop duck farm in Guangdong province, South China. The virus was pathogenic to Muscovy duck embryos and caused severe egg production drop for laying Muscovy ducks. The genome sequence of GD2014 shared 97-99% homologies with other waterfowl-origin Tembusu viruses, and shared 89% identities with MM1775 strain isolated from mosquito. Phylogenetic analysis of entire open reading frame (ORF), E gene and NS5 gene indicated that GD2014 belonged to Ntaya group. These results have implications for understanding the orgin, emergence and pathogenicity of DTMUV as well as for the development of vaccines and diagnostics based on epidemiological data. PMID- 27354304 TI - Identification of a novel Aleutian mink disease virus B-cell epitope using a monoclonal antibody against VP2 protein. AB - Aleutian mink disease virus (AMDV) is a parvovirus that causes an immune complex mediated disease in minks. Capsid protein VP2 is a major structural viral protein and can be used to diagnose AMDV. In this study, a specific monoclonal antibody, 1M13, was produced against the AMDV VP2 protein (amino acids 291-502). A linear VP2-protein epitope was identified by subjecting a series of partially overlapping synthesized peptides to be enzyme-linked immunosorbent assay (ELISA) analysis. The results indicated that (386)HLQQNFSTRYIYD(398) was the minimal linear epitope that could be recognized by mAb 1M13. ELISA assays revealed that mink anti-AMDV sera could also recognize the minimal linear epitope. Sequence alignments demonstrated that the linear epitope is highly conserved among AMDV strains except (386)H and is less conserved among Raccoon dog amdovirus, Gray fox amdovirus, Red fox amdovirus, Bat parvovirus and Mink enteritis parvovirus. Taken together, the generation of this VP2-specific mAb with a defined linear peptide epitope may have potential applications in the development of suitable diagnostic techniques for AMDV. PMID- 27354306 TI - The expression pattern and functional role of REIC/Dkk-3 in the development of cutaneous squamous cell carcinoma. AB - BACKGROUND: The exact physiological function of REIC/Dkk-3 in the development of squamous cell carcinoma(SCC) remains unclear. OBJECTIVE: We aimed to investigate the expression pattern and functional role of REIC/Dkk-3 in the development of SCC. METHODS: We stained normal skin, actinic keratosis (AK) and SCC tissue with REIC/Dkk-3. The proliferation and migration of SCC 12 over-expressed with REIC/Dkk-3 were observed. For in vivo study, SCC12 cells in PBS, SCC12 cells containing LacZ, and REIC/Dkk-3-transduced SCC 12 cells were injected intra dermally into the left and right backside flanks of SCID mice respectively, and tumor growth was evaluated. RESULTS: REIC/Dkk-3 staining was detected throughout the full epidermis in normal skin, focally positive in AK. Negative or very low stain of REIC/Dkk-3 was observed in SCC in situ, keratoacanthoma, and SCC. REIC/Dkk-3 mRNA level in SCC was very low compared with that in normal skin tissue. REIC/Dkk-3 significantly decreased the proliferation and migration of SCC12 cells comparing with control (p<0.05). Cyclin D1 and CDK4/6 expression was slightly lower and p21 was very higher in REIC/Dkk-3-overexpressed group than in the LacZ group. Fewer ITGA6 cells were found in the REIC/Dkk-3 overexpressed group than in the LacZ control (p<0.01). Mean tumor volume was smallest in the REIC/Dkk-3 overexpressed group (p<0.01) 21days after the intradermal injection of SCC12 cells. CONCLUSION: REIC/Dkk-3 could be involved early in SCC development and have inhibitory effect on the development of SCC. PMID- 27354305 TI - Discovery of a novel ROCK2 inhibitor with anti-migration effects via docking and high-content drug screening. AB - Rho-associated protein kinase (ROCK) mediated the reorganization of the actin cytoskeleton and has been implicated in the spread and metastatic process of cancer. In this study, structure-based high-throughput virtual screening was used to identify candidate compounds targeting ROCK2 from a chemical library. Moreover, high-content screening based on neurite outgrowth of SH-SY5Y cells (a human neuroblastoma cell line) was used for accelerating the identification of compounds with characteristics of ROCK2 inhibitors. The effects of bioactive ROCK2 inhibitor candidates were further validated using other bioassays including cell migration and wound healing in SH-SY5Y cells. Through the combined virtual and high-content drug screening, the compound 1,3-benzodioxol-5-yl[1-(5 isoquinolinylmethyl)-3-piperidinyl]-methanone (BIPM) was identified as a novel and potent ROCK2 inhibitor. Exposure of SH-SY5Y cells to BIPM led to significant changes in neurite length, cell migration and actin stress fibers. Further experiments demonstrated that BIPM was able to significantly inhibit phosphorylation of cofilin, a regulatory protein of actin cytoskeleton. These results suggest that BIPM could be considered as a promising scaffold for the further development of ROCK2 inhibitors for anti-cancer metastasis. PMID- 27354307 TI - Acute respiratory distress syndrome in adenovirus type 4 pneumonia: A case report. AB - Human adenoviruses (HAdVs) cause a wide spectrum of clinical syndromes, depending on species and types, from mild respiratory infections to deadly pneumonia: in particular, severe infections occur in immunocompromised patients. In this report, we describe the case of a 36 years-old woman admitted to our intensive care unit (ICU) with severe respiratory distress syndrome caused by adenovirus pneumonia, that required invasive respiratory support (mechanical ventilation and extracorporeal membrane oxygenation). Molecular assays detected the virus in respiratory and plasma specimen and sequencing procedure identified HAdV type 4. Patient improved after cidofovir administration. Leukopenia and subsequent bacterial infection occurred, but the patient recovered completely and was discharged from the hospital after 54days. PMID- 27354308 TI - Great oaks from little acorns grow-21 years of CMI. PMID- 27354309 TI - Targeted loss of SHP1 in murine thymocytes dampens TCR signaling late in selection. AB - SHP1 is a tyrosine phosphatase critical to proximal regulation of TCR signaling. Here, analysis of CD4-Cre SHP1(fl/fl) conditional knockout thymocytes using CD53, TCRbeta, CD69, CD4, and CD8alpha expression demonstrates the importance of SHP1 in the survival of post selection (CD53(+) ), single-positive thymocytes. Using Ca(2+) flux to assess the intensity of TCR signaling demonstrated that SHP1 dampens the signal strength of these same mature, postselection thymocytes. Consistent with its dampening effect, TCR signal strength was also probed functionally using peptides that can mediate selection of the OT-I TCR, to reveal increased negative selection mediated by lower-affinity ligand in the absence of SHP1. Our data show that SHP1 is required for the survival of mature thymocytes and the generation of the functional T-cell repertoire, as its absence leads to a reduction in the numbers of CD4(+) and CD8(+) naive T cells in the peripheral lymphoid compartments. PMID- 27354310 TI - Corrigendum to "Lactoferricin enhances BMP7-stimulated anabolic pathways in intervertebral disc cells" [Gene. 2013 Jul. 25; 524(2):282-91]. PMID- 27354312 TI - Spin-orbit effects on the (119)Sn magnetic-shielding tensor in solids: a ZORA/DFT investigation. AB - Periodic-boundary and cluster calculations of the magnetic-shielding tensors of (119)Sn sites in various co-ordination and stereochemical environments are reported. The results indicate a significant difference between the predicted NMR chemical shifts for tin(ii) sites that exhibit stereochemically-active lone pairs and tin(iv) sites that do not have stereochemically-active lone pairs. The predicted magnetic shieldings determined either with the cluster model treated with the ZORA/Scalar Hamiltonian or with the GIPAW formalism are dependent on the oxidation state and the co-ordination geometry of the tin atom. The inclusion of relativistic effects at the spin-orbit level removes systematic differences in computed magnetic-shielding parameters between tin sites of differing stereochemistries, and brings computed NMR shielding parameters into significant agreement with experimentally-determined chemical-shift principal values. Slight improvement in agreement with experiment is noted in calculations using hybrid exchange-correlation functionals. PMID- 27354311 TI - Anticipatory UPR Activation: A Protective Pathway and Target in Cancer. AB - The endoplasmic reticulum (EnR) stress sensor, the unfolded protein response (UPR), plays a key role in regulating intracellular protein homeostasis. The extensively studied reactive mode of UPR activation is characterized by unfolded protein, or other EnR stress, triggering UPR activation. Here we focus on the emerging anticipatory mode of UPR activation in which mitogenic steroid and peptide hormones and other effectors preactivate the UPR and anticipate a future need for increased protein folding capacity. Mild UPR activation in breast cancer can be protective and contributes to antiestrogen resistance. Hyperactivation of the anticipatory UPR pathway in cancer cells with a small molecule converts it from cytoprotective to cytotoxic, highlighting its potential as a therapeutic target in estrogen receptor-positive breast cancer. PMID- 27354314 TI - Complexity and robustness in hypernetwork models of metabolism. AB - Metabolic reaction data is commonly modelled using a complex network approach, whereby nodes represent the chemical species present within the organism of interest, and connections are formed between those nodes participating in the same chemical reaction. Unfortunately, such an approach provides an inadequate description of the metabolic process in general, as a typical chemical reaction will involve more than two nodes, thus risking oversimplification of the system of interest in a potentially significant way. In this paper, we employ a complex hypernetwork formalism to investigate the robustness of bacterial metabolic hypernetworks by extending the concept of a percolation process to hypernetworks. Importantly, this provides a novel method for determining the robustness of these systems and thus for quantifying their resilience to random attacks/errors. Moreover, we performed a site percolation analysis on a large cohort of bacterial metabolic networks and found that hypernetworks that evolved in more variable environments displayed increased levels of robustness and topological complexity. PMID- 27354313 TI - Google Flu Trends Spatial Variability Validated Against Emergency Department Influenza-Related Visits. AB - BACKGROUND: Influenza is a deadly and costly public health problem. Variations in its seasonal patterns cause dangerous surges in emergency department (ED) patient volume. Google Flu Trends (GFT) can provide faster influenza surveillance information than traditional CDC methods, potentially leading to improved public health preparedness. GFT has been found to correlate well with reported influenza and to improve influenza prediction models. However, previous validation studies have focused on isolated clinical locations. OBJECTIVE: The purpose of the study was to measure GFT surveillance effectiveness by correlating GFT with influenza related ED visits in 19 US cities across seven influenza seasons, and to explore which city characteristics lead to better or worse GFT effectiveness. METHODS: Using Healthcare Cost and Utilization Project data, we collected weekly counts of ED visits for all patients with diagnosis (International Statistical Classification of Diseases 9) codes for influenza-related visits from 2005-2011 in 19 different US cities. We measured the correlation between weekly volume of GFT searches and influenza-related ED visits (ie, GFT ED surveillance effectiveness) per city. We evaluated the relationship between 15 publically available city indicators (11 sociodemographic, two health care utilization, and two climate) and GFT surveillance effectiveness using univariate linear regression. RESULTS: Correlation between city-level GFT and influenza-related ED visits had a median of .84, ranging from .67 to .93 across 19 cities. Temporal variability was observed, with median correlation ranging from .78 in 2009 to .94 in 2005. City indicators significantly associated (P<.10) with improved GFT surveillance include higher proportion of female population, higher proportion with Medicare coverage, higher ED visits per capita, and lower socioeconomic status. CONCLUSIONS: GFT is strongly correlated with ED influenza-related visits at the city level, but unexplained variation over geographic location and time limits its utility as standalone surveillance. GFT is likely most useful as an early signal used in conjunction with other more comprehensive surveillance techniques. City indicators associated with improved GFT surveillance provide some insight into the variability of GFT effectiveness. For example, populations with lower socioeconomic status may have a greater tendency to initially turn to the Internet for health questions, thus leading to increased GFT effectiveness. GFT has the potential to provide valuable information to ED providers for patient care and to administrators for ED surge preparedness. PMID- 27354315 TI - Molecular characterization, expression analysis of the myostatin gene and its association with growth traits in sea cucumber (Apostichopus japonicus). AB - Myostatin (MSTN), also referred to as growth and differentiation factor-8 (GDF 8), is a member of the transforming growth factor-beta superfamily (TGF-beta) and an important negative regulator for skeletal muscle development and growth in vertebrates. However, its function is not clear in invertebrates. In this study, we cloned and analyzed the MSTN gene (Aj-MSTN) from sea cucumber (Apostichopus japonicus). The full-length cDNA sequence of Aj-MSTN gene was composed of 2912bp, which contained a 5' UTR of 487bp, an ORF of 1356bp encoding 452 amino acids and a 3' UTR of 1069bp. The structure of Aj-MSTN included a putative signal peptide, a TGF-beta propeptide domain and a conserved TGF-beta domain. Phylogenetic analysis showed that the Aj-MSTN gene was clustered in the same subgroup with the MSTN-like gene found in Strongylocentrotus purpuratus. Quantitative real-time PCR detection results indicated that the Aj-MSTN gene expressed widely in adult tissues and the highest expression level was observed in the body wall. At different developmental stages, the expression levels were increased significantly at early auricularia and doliolaria stages, and reached the peak at juvenile stage. Six SNPs were identified in 5' flanking region and exons of the Aj-MSTN gene. Association analysis showed that SNP-1, SNP-2 and SNP-4 had significant effects on dry body weight. The results suggested that Aj-MSTN gene could be used as a candidate gene for the selective breeding of A. japonicus. PMID- 27354317 TI - Late stage trifluoromethylthiolation strategies for organic compounds. AB - Substitution by the CF3S group allows for an increase in lipophilicity and electron-withdrawing properties along with an improvement in the bioavailability of medicinal targets; consequently, the late stage introduction of CF3S moieties into medicinal scaffolds is a sought-after strategy in synthetic organic chemistry. Different newly-developed electrophilic and nucleophilic reagents are used to effect the trifluoromethylthiolation of (hetero)aromatic compounds, aliphatic compounds (alkyl, alkenyl, alkynyl substrates), the trifluoromethylthiolation at the alpha- and beta-carbonyl positions, and heteroatoms (N- and S-). Such reactions can involve homolytic substitutions, or functional-group substitutions (ipso). Addition reactions of electrophilic reagents to double and triple bonds followed by ring-cyclizations will be shown to yield relevant CF3S-substituted heteroaromatic compounds with relevant pharmacological action. PMID- 27354316 TI - UtpA and UtpB chaperone nascent pre-ribosomal RNA and U3 snoRNA to initiate eukaryotic ribosome assembly. AB - Early eukaryotic ribosome biogenesis involves large multi-protein complexes, which co-transcriptionally associate with pre-ribosomal RNA to form the small subunit processome. The precise mechanisms by which two of the largest multi protein complexes-UtpA and UtpB-interact with nascent pre-ribosomal RNA are poorly understood. Here, we combined biochemical and structural biology approaches with ensembles of RNA-protein cross-linking data to elucidate the essential functions of both complexes. We show that UtpA contains a large composite RNA-binding site and captures the 5' end of pre-ribosomal RNA. UtpB forms an extended structure that binds early pre-ribosomal intermediates in close proximity to architectural sites such as an RNA duplex formed by the 5' ETS and U3 snoRNA as well as the 3' boundary of the 18S rRNA. Both complexes therefore act as vital RNA chaperones to initiate eukaryotic ribosome assembly. PMID- 27354318 TI - Fabrication of magnetic water-soluble hyperbranched polyol functionalized graphene oxide for high-efficiency water remediation. AB - Magnetic water-soluble hyperbranched polyol functionalized graphene oxide nanocomposite (MWHPO-GO) was successfully prepared and applied to water remediation in this paper. MWHPO-GO was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), magnetization curve, zeta potential, scanning electron microscope (SEM) and transmission electron microscope (TEM) analyses. MWHPO-GO exhibited excellent adsorption performance for the removal of synthetic dyes (methylene blue (MB) and methyl violet (MV)) and heavy metal (Pb(II)). Moreover, MWHPO-GO could be simply recovered from water with magnetic separation. The pseudo-second order equation and the Langmuir model exhibited good correlation with the adsorption kinetic and isotherm data, respectively, for these three pollutants. The thermodynamic results (DeltaG < 0, DeltaH < 0, DeltaS < 0) implied that the adsorption process of MB, MV and Pb(II) was feasible, exothermic and spontaneous in nature. A possible adsorption mechanism has been proposed where pi-pi stacking interactions, H-bonding interaction and electrostatic attraction dominated the adsorption of MB/MV and chelation and electrostatic attraction dominated the adsorption of Pb(II). In addition, the excellent reproducibility endowed MWHPO-GO with the potential for application in water remediation. PMID- 27354319 TI - Management Strategy for Ureteral-Iliac Artery Fistula. AB - BACKGROUND: Ureteral-iliac artery fistula (UIAF) is a rare but a potentially life threatening condition. In this study, we reported our results of UIAF treated by open surgical and endovascular treatment. METHODS: In this single-center, retrospective observational cohort study, we reviewed 6 consecutive patients who were diagnosed with a UIAF and received either open surgical or endovascular treatment based on the specific risk profile of each patient. RESULTS: All patients had an indwelling ureteral stent for a ureteral stricture, with an average ureteral stenting duration of 22 months (range, 1-74 months), and 2 patients had a history of endovascular treatment with stent grafts for UIAF. Contrast-enhanced computed tomographic angiography was positive in 4 patients. Blood and urine cultures were positive in 2 and 4 patients, respectively. Four patients, including 2 with previously failed endovascular treatment, received open surgical repair. The remaining 2 patients received either endovascular treatment with stent grafts or a hybrid procedure. During the mean follow-up period of 20.3 months (range, 6-29 months), there was no symptomatic recurrence of the UIAF. CONCLUSIONS: A multidisciplinary approach is highly preferable for treating potentially life-threatening UIAF. Endovascular treatment with stent grafts is currently recommended in selected patients whenever possible, but open surgical treatment is required in certain patients with enteric contamination, abscess, local sepsis, or previously failed endovascular treatment. PMID- 27354320 TI - Aspiration Thrombectomy of Acute Atrial Fibrillation-related Renal Artery Thromboembolism in a Patient with Horseshoe Kidney. AB - BACKGROUND: Acute arterial thromboembolism to the renal arteries can be treated promptly by local thrombolysis, conventional surgical thrombectomy, or anticoagulation. METHODS: We report a patient who presented with acute loin pain as a result of atrial fibrillation-related thromboembolism to the right renal artery supplying his horseshoe kidney. He was already on warfarin treatment with international normalized ratio of 1.7 and had acute bleeding from malignant peptic ulcer disease, so thrombolysis was contraindicated. RESULTS: He underwent timely endovascular revascularization with aspiration thrombectomy, with good clinical and radiological consequence. He subsequently underwent curative partial gastrectomy and made a steady recovery. CONCLUSION: Early endovascular target directed therapy such as intra-arterial thrombolysis and mechanical aspiration in combination with intravenous heparin therapy will result in renal salvage. PMID- 27354321 TI - Risk Factors for Complications after Peripheral Vascular Surgery in 3,202 Patient Procedures. AB - BACKGROUND: Complications after open vascular surgery are a major health challenge for the healthcare system and the patients. Infrainguinal vascular surgery is often perceived as less risky than aortic surgery and the aim of this study was to identify which risk factors correlated with postoperative complications after open vascular surgery for infrainguinal occlusive disease in an 8-year cohort using the Danish National Vascular Registry (Karbase), which gathers information on all vascular procedures in Denmark. METHODS: This study is a retrospective cohort study. The Karbase was searched for the predefined procedures from January 1, 2005 through December 31, 2012 at our 2 vascular departments. Both elective and urgent surgeries were included. Complications were defined as wound, surgical, or general complication according to Karbase. RESULTS: Three thousand two hundred two procedures were identified. Median age was 70 years and 21% were octogenarians. Sixty percent were male. There was an overall complication rate of 30%, with 19% being wound complications, 6% surgical, and 10% general complications. The greatest risk factors for developing a complication were high age, cardiac and renal disease, high American Society of Anesthesiologists score, and general anesthetics. The 30-day mortality was 5% (1% for claudicants and 8% for acute ischemia) and the 30-day amputation rate was 7% (0.5% for claudicants and 21% for gangrene). CONCLUSIONS: There is a high risk of complication in peripheral vascular surgery. Risk factors are modifiable or nonmodifiable. It is important to identify the risk factors and treat and optimize the patient cardiac and renal status before surgery if time allows, and also to perform surgery in local or regional anesthesia whenever possible, to reduce the risk of postoperative complications. PMID- 27354322 TI - Development of a Decision Tree to Streamline Infrainguinal Vein Graft Surveillance. AB - BACKGROUND: Duplex ultrasound (DU) remains the gold standard for identification and grading of infrainguinal vein graft stenosis. However, DU-based graft surveillance remains controversial. The aim of this study was to develop a decision tree to identify high-risk grafts which would benefit from DU-based surveillance. METHODS: Consecutive patients undergoing infrainguinal vein graft bypass were enrolled in a DU surveillance program. An early postoperative DU was performed at a median of 6 weeks (range 4-9). Based on the findings of this scan and 4 established risk factors for graft failure (diabetes, smoking, infragenicular distal anastomosis, revision bypass surgery), a classification and regression tree (CART) was created to stratify grafts into grafts which are at high and low risk of developing severe stenosis or occlusion. The accuracy of the CART model was evaluated using area under receiver operator characteristic curve (ROC). RESULTS: Of 796 vein graft bypasses performed (760 patients), 64 grafts were occluded by the first surveillance visit and 732 vein grafts were entered into surveillance program. The CART model stratified 299 grafts (40.8%) as low risk and 433 (59.2%) as high-risk grafts. One hundred twenty-six (17.2%) developed critical vein graft stenosis. Overall, 30-month primary patency, primary-assisted and secondary patency rates were 76.2%, 83.6%, and 85.3%, respectively. The area under ROC curve for the CART model was 0.88 (95% confidence interval 0.81-0.94). Primary graft patency rates were higher in low risk versus high-risk grafts (log rank 186, P < 0.0001). Amputation rates were significantly higher in the high-risk grafts compared with low-risk ones (log rank 118, P < 0.0001). CONCLUSION: A clinical decision rule based on readily available clinical data and the findings of significant flow abnormalities on an early postoperative DU scan successfully identifies grafts at high risk of failure and will contribute to safely improving the efficacy of infrainguinal vein graft surveillance services. PMID- 27354323 TI - Time to Wound Healing and Major Adverse Limb Events in Patients with Critical Limb Ischemia Treated with Endovascular Revascularization. AB - BACKGROUND: There are few studies that quantify the impact of time to wound healing on outcomes after endovascular revascularization of critical limb ischemia (CLI). METHODS: In this retrospective study, 179 patients with CLI and tissue loss were assessed for adverse events after endovascular therapy. Associations between time to wound healing and outcomes were determined via Cox proportional hazards analysis. The long-term probability of events was assessed with Kaplan-Meier analysis. The primary end point was major adverse limb events (MALE-major amputation, surgical endarterectomy, or bypass). Secondary end points were major amputation, need for repeat endovascular therapy, and mortality. RESULTS: After multivariable adjustment for time-dependent wound healing, age, renal function, diabetes, and Rutherford class, independent predictors of MALE included the presence of an unhealed wound (hazard ratio [HR], 5.2; 95% confidence interval (CI), 2.3-11.8; P < 0.0001) and creatinine >= 2.0 (HR, 2.4; 95% CI, 1.4-4.3; P = 0.003). On Kaplan-Meier analysis, the probability of MALE was greater in patients with unhealed wounds compared with healed wounds (log rank P < 0.0001). Patients whose wounds healed within 4 months had a lower probability of MALE than patients who did not heal by 4 months (log-rank, P = 0.04). Unhealed wounds were also independently associated with major amputation (HR, 9.0; 95% CI, 2.6-31.1; P = 0.0004), and patients whose wounds healed by 3 months had less major amputation (log-rank, P = 0.04). Unhealed wounds were independently associated with increased risk of mortality (HR, 42.7; 95% CI, 5.7 319.0; P = 0.002) but not repeat revascularization. CONCLUSIONS: Unhealed wounds are an independent risk factor for MALE, major amputation, and mortality after endovascular treatment of CLI. Wound healing within 3 months is associated with less risk of major amputation, and within 4 months less risk of MALE. A focus should be on achieving wound healing as fast as possible in this population. PMID- 27354324 TI - Ni-based heterogeneous catalyst from a designed molecular precursor for the efficient electrochemical water oxidation. AB - Bimetallic Ni-Mo alkoxide was synthesized and exploited as the single-source precursor for the solution-processed deposition of the mixed-oxide layers on different conducting surfaces. Upon potential cycling in 1 M NaOH, these composites convert, in situ, into highly porous NiOx/NiOOH catalysts characterized by the high electrocatalytic activity for water oxidation under both basic (pH 13.6) and near neutral (pH 9.2) conditions. PMID- 27354325 TI - Near-Infrared-to-Visible Photon Upconversion Sensitized by a Metal Complex with Spin-Forbidden yet Strong S0-T1 Absorption. AB - Near-infrared (NIR)-to-visible (vis) photon upconversion (UC) is useful for various applications; however, it remains challenging in triplet-triplet annihilation-based UC, mainly due to the energy loss during the S1-to-T1 intersystem crossing (ISC) of molecular sensitizers. In this work, we circumvent this energy loss by employing a sensitizer with direct S0-to-T1 absorption in the NIR region. A mixed solution of an osmium complex having a strong S0-T1 absorption and rubrene emitter upconverts NIR light (lambda = 938 nm) to visible light (lambda = 570 nm). Sensitizer-doped emitter nanoparticles are prepared by re-precipitation and dispersed into an oxygen-barrier polymer. The obtained composite film shows a stable NIR-to-vis UC emission based on triplet energy migration (TEM), even in air. A high UC quantum yield of 3.1% is observed for this TEM-UC system, expanding the scope of molecular sensitizers for NIR-to-vis UC. PMID- 27354326 TI - A fossil Diploglossus (Squamata, Anguidae) lizard from Basse-Terre and Grande Terre Islands (Guadeloupe, French West Indies). AB - Today, Diploglossine lizards (Anguidae) are common on the Greater Antillean Islands (West Indies), where they are represented by many endemic species. However these lizards are very rare on the Lesser Antillean Islands, where they are only represented by a single species, the Montserrat galliwasp (Diploglossus montisserrati). Here, we show that diploglossine lizards were present in the past on other Lesser Antillean islands, by reporting the discovery of Anguidae fossil remains in two Amerindian archaeological deposits and in a modern deposit. These remains are compared to skeletons of extant diploglossine lizards, including D. montisserrati, using X-ray microtomography of the type specimen of this critically endangered lizard. We also conducted a histological study of the osteoderms in order to estimate the putative age of the specimen. Our results show that the fossil specimens correspond to a member of the Diploglossus genus presenting strong similarities, but also minor morphological differences with D. montisserrati, although we postulate that these differences are not sufficient to warrant the description of a new species. These specimens, identified as Diploglossus sp., provide a new comparison point for the study of fossil diploglossine lizards and reflect the historical 17(th) century mentions of anguid lizards, which had not been observed since. PMID- 27354327 TI - M1761K mutation in the von Willebrand factor A3 domain associated with impaired collagen binding and without platelet dysfunction. PMID- 27354328 TI - Osteoporosis: The Result of an 'Aged' Bone Microenvironment. AB - Osteoporosis is an age-related progressive bone disease. Recent advances in epigenetics, cell biology, osteoimmunology, and genetic epidemiology have unraveled new mechanisms and players underlying the pathology of osteoporosis, supporting a model of age-related dysregulation and crosstalk in the bone microenvironment. PMID- 27354329 TI - The effect of overhead target on the lower limb biomechanics during a vertical drop jump test in elite female athletes. PMID- 27354330 TI - Successful out-of-hospital therapy for heatstroke in three marathon runners with a novel core body cooling device: CAERvest((r)). PMID- 27354331 TI - Exercise as medicine for people with epilepsy. PMID- 27354332 TI - Retromolar foramen: an anatomical study with clinical considerations. AB - The retromolar canal and foramen, an anatomical variation in the mandibular retromolar area, houses and transmits neurovascular elements that may innervate the mandibular third molar and associated tissues. These structures have been implicated in local anaesthetic failure, loss of sensation in the normal distribution of the buccal nerve, and local haemorrhage during surgery. Examination of 885 dry mandibles showed that 70 had a retromolar foramen (8%). There were no significant differences between groups according to age, sex, or ancestry. The mean (SD) distance from molar to retromolar foramen was 16.8 (5.6) mm for the mandibular second molar and 10.5 (3.8) mm for the mandibular third molar. The link between these structures and failure of local anaesthesia seems tenuous at best. Bleeding may not represent a serious complication. Although there may be a possibility of perineural spread of infective and invasive pathology, we know of no reported cases. The only clear evidence of complications associated with a confirmed retromolar foramen seems to be loss of sensation in the normal distribution of the buccal nerve. Even though the retromolar foramen does not seem to be of great clinical importance, it could be a source of anxiety for the inexperienced practitioner. PMID- 27354334 TI - Shape and size controlled synthesis of uniform iron oxide nanocrystals through new non-hydrolytic routes. AB - New, non-hydrolytic routes to synthesize highly crystalline iron oxide nanocrystals (8-40 nm, magnetite) are described in this report whereby particle size and morphology were precisely controlled through reactant (precursor, e.g. (FeO(OH)) ratios, co-surfactant and organic additive, and/or reaction time. Particle size, with high monodispersivity (<10%), is demonstrated to be a function of precursor concentrations and through the addition of different cosurfactants and/or additives, cubic, octahedral, potato-like, and flower-like iron oxide nanocrystals can be reproducibly synthesized through simple one-pot thermal decomposition methods. High resolution transmission electron microscope, x-ray diffraction, and superconducting quantum interference device were used to characterize the size, structure and magnetic properties of the resulting nanocrystals. For aqueous applications, materials synthesized/purified in organic solvents are broadly water dispersible through a variety of phase (aqueous) transfer method(s). PMID- 27354333 TI - Featured Article: Alterations of lecithin cholesterol acyltransferase activity and apolipoprotein A-I functionality in human sickle blood. AB - In sickle cell disease (SCD) cholesterol metabolism appears dysfunctional as evidenced by abnormal plasma cholesterol content in a subpopulation of SCD patients. Specific activity of the high density lipoprotein (HDL)-bound lecithin cholesterol acyltransferase (LCAT) enzyme, which catalyzes esterification of cholesterol, and generates lysoPC (LPC) was significantly lower in sickle plasma compared to normal. Inhibitory amounts of LPC were present in sickle plasma, and the red blood cell (RBC) lysophosphatidylcholine acyltransferase (LPCAT), essential for the removal of LPC, displayed a broad range of activity. The functionality of sickle HDL appeared to be altered as evidenced by a decreased HDL-Apolipoprotein A-I exchange in sickle plasma as compared to control. Increased levels of oxidized proteins including ApoA-I were detected in sickle plasma. In vitro incubation of sickle plasma with washed erythrocytes affected the ApoA-I-exchange supporting the view that the RBC blood compartment can affect cholesterol metabolism in plasma. HDL functionality appeared to decrease during acute vaso-occlusive episodes in sickle patients and was associated with an increase of secretory PLA2, a marker for increased inflammation. Simvastatin treatment to improve the anti-inflammatory function of HDL did not ameliorate HDL ApoA-I exchange in sickle patients. Thus, the cumulative effect of an inflammatory and highly oxidative environment in sickle blood contributes to a decrease in cholesterol esterification and HDL function, related to hypocholesterolemia in SCD. PMID- 27354335 TI - Mastitis vaccination using a commercial polyvalent vaccine or a herd-specific Staphylococcus aureus vaccine. Results of a controlled field trial on a dairy farm. AB - Objective of this study was the improvement of selected parameters of udder health by mastitis vaccination in a dairy herd with elevated bulk milk somatic cell counts and Staphylococcus (S.) aureus as predominant mastitis causing pathogen. MATERIAL AND METHODS: On a dairy farm, pregnant heifers (status group [SG] 1; n = 181) as well as cows stratified for their udder health state (classification based on results of cytobacteriological investigations of quarter milk samples obtained before dry cow therapy [MS0]) (SG 2-4; n = 416) were randomly assigned to one of the following vaccination groups (VG): Startvac(r) (VG SV), Bestvac(r) Rind Mastitis (containing herd-specific S. aureus-strains; VG BV) and the unvaccinated control (VG Co, placebo), respectively. The collected data (5 [MS5] and 52 [MS52] days in milk [DIM]: quarter milk somatic cell count [QSCC] and bacteriological investigation of quarter milk samples; dairy herd improvement test [DHIT] days 1-10: milk yield and individual cow somatic cell count; until 305 DIM: clinical mastitis cases) were compared between the VG within their SG. RESULTS: S. aureus prevalences were significantly lower in VG SV (p < 0.001) and VG BV (p = 0.006) within SG 3 and in VG SV (p = 0.008) within SG 4, respectively, in comparison to VG Co. Milk yields (DHIT days [p = 0.042] and 305-day milk yield [p = 0.040]) were significantly less in VG SV within SG 4 compared to VG Co. Significant different changes over time in comparison to VG Co indicating a vaccine effect during lactation were only observed for QSCC within SG 4 for VG BV (p = 0.017; increase towards MS52) and for S. aureus prevalence within SG 3 for VG BV (p < 0.001; opposing trends from MS0 towards MS52). All other interactions of time and VG under investigation were not significant in any of the SG. Furthermore, there were no descriptive differences in the incidence of clinical mastitis and duration of a necessary mastitis therapy, respectively, between the VG within their SG. CONCLUSION: In this field study, the application of two different mastitis vaccines was not an appropriate tool to improve the considered parameters of udder health sustainably. PMID- 27354336 TI - Conceptualizing the key processes of Mindful Parenting and its application to youth mental health. AB - OBJECTIVE: Youth mental health disorders are rising across the world. Mindful Parenting could be a potential tool to promote youth mental health. The primary distinction between Mindful Parenting programs and other behavioral parenting programs is the focus on emotional literacy and compassion. However, this emerging field has gaps in its theory and evidence. In order to objectively evaluate the impact of Mindful Parenting, it is important to identify how it promotes change. This theoretical paper aims to articulate the key change processes of Mindful Parenting that promote positive outcomes. METHOD: A literature review was conducted to synthesize the change processes outlined by different authors in the field. RESULTS: Key processes argued to promote Mindful Parenting were aligned with five main categories, namely attention, intention, attitude, attachment and emotion. More specifically the change processes were listening, emotional awareness, emotional regulation, attentional regulation, attunement, attention to variability, intentionality, reperceiving, compassion and non-judgmental acceptance. CONCLUSIONS: This preliminary analysis attempted to understand how Mindful Parenting fosters change and transformation. Whilst there are numerous change processes, the essence of Mindful Parenting appears to be the ability to be responsive to a child's needs. PMID- 27354338 TI - New records of larval stages of the eel cod genus Muraenolepis Gunther 1880 (Gadiformes: Muraenolepididae) from the western Antarctic Peninsula. AB - Three newly discovered larval specimens of the genus Muraenolepis collected from the waters of the western Antarctic Peninsula are described. Knowledge of their natural history is sparse and information about their early life history is based on only a few larval stages. Here, the available literature on larval eel cods is reviewed, and the specimens placed in context. PMID- 27354337 TI - Tumor- and Neoantigen-Reactive T-cell Receptors Can Be Identified Based on Their Frequency in Fresh Tumor. AB - Adoptive transfer of T cells with engineered T-cell receptor (TCR) genes that target tumor-specific antigens can mediate cancer regression. Accumulating evidence suggests that the clinical success of many immunotherapies is mediated by T cells targeting mutated neoantigens unique to the patient. We hypothesized that the most frequent TCR clonotypes infiltrating the tumor were reactive against tumor antigens. To test this hypothesis, we developed a multistep strategy that involved TCRB deep sequencing of the CD8(+)PD-1(+) T-cell subset, matching of TCRA-TCRB pairs by pairSEQ and single-cell RT-PCR, followed by testing of the TCRs for tumor-antigen specificity. Analysis of 12 fresh metastatic melanomas revealed that in 11 samples, up to 5 tumor-reactive TCRs were present in the 5 most frequently occurring clonotypes, which included reactivity against neoantigens. These data show the feasibility of developing a rapid, personalized TCR-gene therapy approach that targets the unique set of antigens presented by the autologous tumor without the need to identify their immunologic reactivity. Cancer Immunol Res; 4(9); 734-43. (c)2016 AACR. PMID- 27354339 TI - A novel homozygous PAM16 mutation in a patient with a milder phenotype and longer survival. PMID- 27354340 TI - Influence of transvaginal ultrasound-guided follicular punctures in the mare on heart rate, respiratory rate, facial expression changes, and salivary cortisol as pain scoring. AB - Transvaginal ultrasound-guided follicular punctures are widely used in the mare for diagnosis, research, and commercial applications. The objective of our study was to determine their influence on pain, stress, and well-being in the mare, by evaluating heart rate, breath rate, facial expression changes, and salivary cortisol before, during, and after puncture. For this experiment, 21 pony mares were used. Transvaginal ultrasound-guided aspirations were performed on 11 mares. After injections for sedation, analgesia, and antispasmodia, the follicles from both ovaries were aspirated with a needle introduced through the vagina wall into the ovary. In the control group, 10 mares underwent similar treatments and injections, but no follicular aspiration. Along the session, heart rate and breath rate were evaluated by a trained veterinarian, ears position, eyelid closure, and contraction of facial muscles were evaluated, and salivary samples were taken for evaluation of cortisol concentration. A significant relaxation was observed after sedative injection in the punctured and control mares, according to ear position, eyelid closure, and contraction of facial muscles, but no difference between punctured and control animals was recorded. No significant modification of salivary cortisol concentration during puncture and no difference between punctured and control mares at any time were observed. No significant modification of the breath rate was observed along the procedure for the punctured and the control mares. Heart rate increased significantly but transiently when the needle was introduced in the ovary and was significantly higher at that time for the punctured mares than that for control mares. None of the other investigated parameters were affected at that time, suggesting discomfort is minimal and transient. Improving analgesia, e.g., through a multimodal approach, during that possibly more sensitive step could be recommended. The evaluation of facial expression changes and heart rate is easy to-use and accurate tools to evaluate pain and well-being of the mare. PMID- 27354341 TI - Fetal gender prediction based on maternal plasma testosterone and insulin-like peptide 3 concentrations at midgestation and late gestation in cattle. AB - We compared maternal plasma testosterone and insulin-like peptide 3 (INSL3) concentrations between dams carrying a male versus female fetus from early to late gestation and examined the application of maternal hormonal concentrations to fetal gender prediction in dairy and beef cattle. Blood samples were collected from Holstein cows or heifers (N = 31) and Japanese Black beef cows (N = 33) at 1 month intervals at 2 to 8 months of gestation. Fetal gender was confirmed by visual observation of external genitalia of calves just after birth. Plasma testosterone and INSL3 concentrations were determined by enzyme-immunoassay. Fetal genders were judged based on cutoff values of maternal testosterone and INSL3 concentrations (male, if it was >= cutoff value; female, if < cutoff value), which we set for each hormone at each gestational month using receiver operating characteristic curves. Plasma testosterone concentrations were higher for dams with a male fetus than those with a female at 4, 5, 7, and 8 months for the dairy cattle (P < 0.05) and at 4, 5, 6, and 8 months for the beef cows (P < 0.05). Plasma INSL3 concentrations were higher for dams with a male fetus than those with a female at 2 and 6 months for the dairy cattle (P < 0.05) and at 4 to 8 months for the beef cows (P < 0.05). The predictive values and detection rates for fetal gender prediction based on maternal testosterone concentrations were 75.8% to 79.3% for dairy cattle at 5 and 7 months and for beef cows at 5 and 6 months, whereas those values by maternal INSL3 concentrations were 71.0% to 72.4% for the dairy cattle at 6 months and beef cows at 4 and 8 months. When multiple time points of testosterone and INSL3 concentrations at several midgestation and late gestation months were considered for fetal gender prediction, predictive values were 89.3% (5-7 months) and 85.7% to 88.0% (4-6, 8 months) for the dairy and beef breeds, respectively. Maternal testosterone and INSL3 concentrations in dams carrying a male fetus were higher than those carrying a female at midgestation and/or late gestation in Holstein and Japanese Black beef cattle. Nearly, 80% accuracy was obtained for fetal gender prediction by a single time point of maternal plasma testosterone concentrations at midgestation. Nearly 90% accuracy for the prediction was obtained when multiple time points of testosterone and INSL3 concentrations from midgestation to late gestation were considered. PMID- 27354343 TI - Cortical gene expression correlates of temporal lobe epileptogenicity. AB - INTRODUCTION: Despite being one of the most common neurological diseases, it is unknown whether there may be a genetic basis to temporal lobe epilepsy (TLE). Whole genome analyses were performed to test the hypothesis that temporal cortical gene expression differs between TLE patients with high vs. low baseline seizure frequency. METHODS: Baseline seizure frequency was used as a clinical measure of epileptogenicity. Twenty-four patients in high or low seizure frequency groups (median seizures/month) underwent anterior temporal lobectomy with amygdalohippocampectomy for intractable TLE. RNA was isolated from the lateral temporal cortex and submitted for expression analysis. Genes significantly associated with baseline seizure frequency on likelihood ratio test were identified based on >0.90 area under the ROC curve, P value of <0.05. RESULTS: Expression levels of forty genes were significantly associated with baseline seizure frequency. Of the seven most significant, four have been linked to other neurologic diseases. Expression levels associated with high seizure frequency included low expression of Homeobox A10, Forkhead box A2, Lymphoblastic leukemia derived sequence 1, HGF activator, Kelch repeat and BTB (POZ) domain containing 11, Thanatos-associated protein domain containing 8 and Heparin sulfate (glucosamine) 3-O-sulfotransferase 3A1. CONCLUSIONS: This study describes novel associations between forty known genes and a clinical marker of epileptogenicity, baseline seizure frequency. Four of the seven discussed have been previously related to other neurologic diseases. Future investigation of these genes could establish new biomarkers for predicting epileptogenicity, and could have significant implications for diagnosis and management of temporal lobe epilepsy, as well as epilepsy pathogenesis. PMID- 27354342 TI - TGFbeta-Responsive HMOX1 Expression Is Associated with Stemness and Invasion in Glioblastoma Multiforme. AB - Glioblastoma multiforme (GBM) is the most common and lethal adult brain tumor. Resistance to standard radiation and chemotherapy is thought to involve survival of GBM cancer stem cells (CSCs). To date, no single marker for identifying GBM CSCs has been able to capture the diversity of CSC populations, justifying the needs for additional CSC markers for better characterization. Employing targeted mass spectrometry, here we present five cell-surface markers HMOX1, SLC16A1, CADM1, SCAMP3, and CLCC1 which were found to be elevated in CSCs relative to healthy neural stem cells (NSCs). Transcriptomic analyses of REMBRANDT and TCGA compendiums also indicated elevated expression of these markers in GBM relative to controls and non-GBM diseases. Two markers SLC16A1 and HMOX1 were found to be expressed among pseudopalisading cells that reside in the hypoxic region of GBM, substantiating the histopathological hallmarks of GBM. In a prospective study (N = 8) we confirmed the surface expression of HMOX1 on freshly isolated primary GBM cells (P0). Employing functional assays that are known to evaluate stemness, we demonstrate that elevated HMOX1 expression is associated with stemness in GBM and can be modulated through TGFbeta. siRNA-mediated silencing of HMOX1 impaired GBM invasion-a phenomenon related to poor prognosis. In addition, surgical resection of GBM tumors caused declines (18% +/- 5.1SEM) in the level of plasma HMOX1 as measured by ELISA, in 8/10 GBM patients. These findings indicate that HMOX1 is a robust predictor of GBM CSC stemness and pathogenesis. Further understanding of the role of HMOX1 in GBM may uncover novel therapeutic approaches. Stem Cells 2016;34:2276-2289. PMID- 27354344 TI - A simplified and reproducible method to size the mitral annulus: implications for transcatheter mitral valve replacement. AB - Aims: Transcatheter mitral valve replacement (TMVR) provides definitive valve replacement through a minimally invasive procedure. In the setting of TMVR, it remains unclear how relevant the differences between different mitral annular (MA) diameters are. We sought to define a simplified and reproducible method to describe the MA size. Methods and results: Using cardiac computed tomography angiography (CTA) studies of 47 patients, 3D MA perimeter (P3D) was annotated. The aorto-mitral continuity was excluded from MA contour either by manual annotation (yielding a saddle-shape model) or by simple truncation at the medial and lateral trigones (yielding a D-shape model). The method of the least squares was used to generate the projected MA area (Aproj) and perimeter (Pproj). Intercommissural (IC) and septolateral (SL) diameters, Dmean = (IC diameter + SL diameter)/2, area-derived diameter (DArea = 2 x ?(A/pi)) and perimeter-derived diameter (DPerimeter = P/pi) were measured. MA eccentricity, height, and calcification (MAC) were assessed. Thirty studies were re-read by the same and by another observer to test intra- and inter-observer reproducibility. Patients (age, 75 +/- 12 years, 66% males) had a wide range of mitral regurgitation severity (none-trace in 8%, mild in 55%, moderate-severe in 37%), MA size (area: 5-16 cm2), eccentricity (-8-52%), and height (3-11 mm). MAC was seen in 11 cases, in whom MAC arc occupied 26 +/- 20% of the MA circumference. DArea (36.0 +/- 4.0 mm) and DPerimeter (37.1 +/- 3.8 mm) correlated strongly (R2 = 0.97) and were not significantly different (P = 0.15). The IC (39.3 +/- 4.6 mm) and the SL (31.4 +/- 4.5 mm) diameters were significantly different from DArea (P < 0.001) while Dmean (35.4 +/- 4.0 mm) was not (P = 0.5). The correlation of DArea was stronger with Dmean (R2 = 0.96) than with IC and SL diameters (R2 = 0.69 and 0.76, respectively). The average difference between DArea and Dmean was +0.6 mm and the 95% limits of agreement were 2.1 and -0.9 mm. Similar results were found when the D-shape model was applied. All MA diameters showed good reproducibility with high intraclass correlation coefficient (0.93-0.98), small average bias (0.37-1.1 mm), and low coefficient of variation (3-7%) for intra- and inter-observer comparisons. Reproducibility of DArea was lower in patients with MAC. Conclusion: MA sizing by CTA is readily feasible and reproducible. Dmean is a simple index that can be used to infer the effective MA size. PMID- 27354345 TI - Diagnostic performance of on-site CT-derived fractional flow reserve versus CT perfusion. AB - Aims: To compare the diagnostic accuracy of on-site computed tomography (CT) derived fractional flow reserve (FFR) and stress CT myocardial perfusion (CTP) in patients with coronary artery disease. Methods and results: Using a prospective CTP registry, 72 patients with invasive FFR were enrolled. CT-derived FFR was computed on-site using rest-phase CTP data. The diagnostic accuracies of coronary CT angiography (CCTA), CT-derived FFR, and stress CTP were evaluated using an area under the receiver-operating characteristic curve (AUC) with invasive FFR as a reference standard. Logistic regression and the net reclassification index (NRI) were used to evaluate incremental differences in CT-derived FFR or CTP compared with CCTA alone. The per-vessel prevalence of haemodynamically significant stenosis (FFR <= 0.80) was 39% (54/138). Per-vessel sensitivity and specificity were 94 and 66% for CCTA, 87 and 77% for CT-derived FFR, and 79 and 91% for CTP, respectively. There was no significant difference in the AUC values of CT-derived FFR and CTP (P = 0.845). The diagnostic performance of CCTA (AUC = 0.856) was improved by combining it with CT-derived FFR (AUC = 0.919, P = 0.004, NRI = 1.01) or CTP (AUC = 0.913, P = 0.004, NRI = 0.66). CT-derived FFR values had a moderate correlation with invasive FFR (r = 0.671, P < 0.001). Conclusion: On-site CT-derived FFR combined with CCTA provides an incremental diagnostic improvement over CCTA alone in identifying haemodynamically significant stenosis defined by invasive FFR, with a diagnostic accuracy comparable with CTP. PMID- 27354346 TI - Venturing into new realms? Microorganisms in space. AB - One of the biggest challenges of science is the determination of whether extraterrestrial life exists. Although potential habitable areas might be available for complex life, it is more likely that microbial life could exist in space. Many extremotolerant and extremophilic microbes have been found to be able to withstand numerous, combined environmental factors, such as high or low temperatures and pressures, high-salt conditions, high doses of radiation, desiccation or nutrient limitations. They may even survive the transit from one planet to another. Terrestrial Mars-analogue sites are one focus of researchers, in order to understand the microbial diversity in preparation for upcoming space missions aimed at the detection of life. However, such missions could also pose a risk with respect to contamination of the extraterrestrial environment by accidentally transferred terrestrial microorganisms. Closer to the Earth, the International Space Station is the most enclosed habitat, where humans work and live-and with them numerous microorganisms. It is still unknown how microbes adapt to this environment, possibly even creating a risk for the crew. Information on the microbiology of the ISS will have an impact on the planning and implementation of long-term human spaceflights in order to ensure a safe, stable and balanced microbiome on board. PMID- 27354349 TI - The Yin and Yang of codon usage. AB - The genetic code is degenerate. With the exception of two amino acids (Met and Trp), all other amino acid residues are each encoded by multiple, so-called synonymous codons. Synonymous codons were initially presumed to have entirely equivalent functions, however, the finding that synonymous codons are not present at equal frequencies in genes/genomes suggested that codon choice might have functional implications beyond amino acid coding. The pattern of non-uniform codon use (known as codon usage bias) varies between organisms and represents a unique feature of an organism. Organism-specific codon choice is related to organism-specific differences in populations of cognate tRNAs. This implies that, in a given organism, frequently used codons will be translated more rapidly than infrequently used ones and vice versa A theory of codon-tRNA co-evolution (necessary to balance accurate and efficient protein production) was put forward to explain the existence of codon usage bias. This model suggests that selection favours preferred (frequent) over un-preferred (rare) codons in order to sustain efficient protein production in cells and that a given un-preferred codon will have the same effect on an organism's fitness regardless of its position within an mRNA's open reading frame. However, many recent studies refute this prediction. Un-preferred codons have been found to have important functional roles and their effects appeared to be position-dependent. Synonymous codon usage affects the efficiency/stringency of mRNA decoding, mRNA biogenesis/stability, and protein secretion and folding. This review summarizes recent developments in the field that have identified novel functions of synonymous codons and their usage. PMID- 27354350 TI - Looking beyond the genes: the role of non-coding variants in human disease. AB - Over the past decades the search for disease causing variants has been focusing exclusively on the coding genome. This highly selective approach has been extremely successful resulting in the identification of thousands of disease genes, but ignores the functional and therefore disease relevance of the rest of the genome. Dropping sequencing costs and new high-throughput technologies such as ChIP-seq and chromosome conformation capture have opened new possibilities for the systematic investigation of the non-coding genome. These data have revealed the importance of non-coding DNA in fundamental processes such as gene regulation and 3D chromatin folding. Research into the principles of chromatin folding has revealed a domain structure of the genome, called topologically associated domains that provide a scaffold for enhancer promoter contacts. Non-coding mutations that affect regulatory elements can affect gene regulation by a loss of function, resulting in reduced gene expression, or a gain of function resulting in gene mis- or overexpression. Structural variations such as deletions, inversions or duplications have the potential to disturb normal chromatin folding. This may lead to the repositioning or disruption of topological associating domains and the relocation of enhancer elements with consecutive gene misexpression. Several recent studies highlight this as important disease mechanisms in developmental disorders and cancer. Therefore, the regulatory landscape of the genome has to be taken into consideration when investigating the pathology of human disease. In this review, we will discuss the recent discoveries in the field of non-coding variation, gene regulation, 3D genome architecture, and their implications for human genetics. PMID- 27354348 TI - Specificity and complexity in bacterial quorum-sensing systems. AB - Quorum sensing (QS) is a microbial cell-to-cell communication process that relies on the production and detection of chemical signals called autoinducers (AIs) to monitor cell density and species complexity in the population. QS allows bacteria to behave as a cohesive group and coordinate collective behaviors. While most QS receptors display high specificity to their AI ligands, others are quite promiscuous in signal detection. How do specific QS receptors respond to their cognate signals with high fidelity? Why do some receptors maintain low signal recognition specificity? In addition, many QS systems are composed of multiple intersecting signaling pathways: what are the benefits of preserving such a complex signaling network when a simple linear 'one-to-one' regulatory pathway seems sufficient to monitor cell density? Here, we will discuss different molecular mechanisms employed by various QS systems that ensure productive and specific QS responses. Moreover, the network architectures of some well characterized QS circuits will be reviewed to understand how the wiring of different regulatory components achieves different biological goals. PMID- 27354347 TI - Cyclic diguanylate signaling in Gram-positive bacteria. AB - The nucleotide second messenger 3'-5' cyclic diguanylate monophosphate (c-di-GMP) is a central regulator of the transition between motile and non-motile lifestyles in bacteria, favoring sessility. Most research investigating the functions of c di-GMP has focused on Gram-negative species, especially pathogens. Recent work in Gram-positive species has revealed that c-di-GMP plays similar roles in Gram positives, though the precise targets and mechanisms of regulation may differ. The majority of bacterial life exists in a surface-associated state, with motility allowing bacteria to disseminate and colonize new environments. c-di-GMP signaling regulates flagellum biosynthesis and production of adherence factors and appears to be a primary mechanism by which bacteria sense and respond to surfaces. Ultimately, c-di-GMP influences the ability of a bacterium to alter its transcriptional program, physiology and behavior upon surface contact. This review discusses how bacteria are able to sense a surface via flagella and type IV pili, and the role of c-di-GMP in regulating the response to surfaces, with emphasis on studies of Gram-positive bacteria. PMID- 27354351 TI - Cyclooxygenase-2 deficiency impairs muscle-derived stem cell-mediated bone regeneration via cellular autonomous and non-autonomous mechanisms. AB - This study investigated the role of cyclooxygenase-2 (COX-2) expression by donor and host cells in muscle-derived stem cell (MDSC)-mediated bone regeneration utilizing a critical size calvarial defect model. We found that BMP4/green fluorescent protein (GFP)-transduced MDSCs formed significantly less bone in COX 2 knock-out (Cox-2KO) than in COX-2 wild-type (WT) mice. BMP4/GFP-transduced Cox 2KO MDSCs also formed significantly less bone than transduced WT MDSCs when transplanted into calvarial defects created in CD-1 nude mice. The impaired bone regeneration in the Cox-2KO MDSCBMP4/GFP group is associated with downregulation of BMP4-pSMAD1/5 signaling, decreased osteogenic differentiation and lowered proliferation capacity after transplantation, compared with WT MDSCBMP4/GFP cells. The Cox-2KO MDSCBMP4/GFP group demonstrated a reduction in cell survival and direct osteogenic differentiation in vitro These effects were mediated in part by the downregulation of Igf1 and Igf2. In addition, the Cox-2KO MDSCBMP4/GFP cells recruited fewer macrophages than the WT MDSC/BMP4/GFP cells in the early phase after injury. We concluded that the bone regeneration capacity of Cox-2KO MDSCs was impaired because of a reduction in cell proliferation and survival capacities, reduction in osteogenic differentiation and a decrease in the ability of the cells to recruit host cells to the injury site. PMID- 27354353 TI - Natural killer cell memory in context. AB - Immune memory has traditionally been considered a hallmark of vertebrate T and B lymphocytes. However, given the advantage in mounting quicker and more robust responses to recurrent infection, it is unsurprising that alternative strategies of memory are found in various immune cells throughout the evolutionary tree. In this context, a variety of NK cell memory subsets have recently been identified. Mouse models of cytomegalovirus infection have been instrumental in revealing the kinetics and molecular mechanisms of long-lived NK cell memory. Moreover, murine liver-resident memory NK cell subsets have been identified that potentially harbour antigen-specificity. Phenotypic counter-parts have recently been characterised in the human liver, adding to the mounting evidence suggesting that a spectrum of NK cell memory subsets exist in primates. These include cytomegalovirus-associated peripheral blood NK cell expansions that in humans have been shown to harbour epigenetic alterations that impact cellular phenotype and function. Here we discuss some general mechanisms of non-classical immune memory. We highlight themes of commonality that may yield clues to the molecular mechanisms of NK cell memory, whilst emphasising some outstanding questions. PMID- 27354352 TI - Genome-wide association study in East Asians identifies two novel breast cancer susceptibility loci. AB - Breast cancer is one of the most common malignancies among women worldwide. Genetic factors have been shown to play an important role in breast cancer aetiology. We conducted a two-stage genome-wide association study (GWAS) including 14 224 cases and 14 829 controls of East Asian women to search for novel genetic susceptibility loci for breast cancer. Single nucleotide polymorphisms (SNPs) in two loci were found to be associated with breast cancer risk at the genome-wide significance level. The first locus, represented by rs12118297 at 1p22.3 (near the LMO4 gene), was associated with breast cancer risk with odds ratio (OR) and (95% confidence interval (CI)) of 0.91 (0.88-0.94) and a P-value of 4.48 * 10- 8 This association was replicated in another study, DRIVE GAME-ON Consortium, including 16 003 cases and 41 335 controls of European ancestry (OR = 0.95, 95% CI = 0.91-0.99, P-value = 0.019). The second locus, rs16992204 at 21q22.12 (near the LINC00160 gene), was associated with breast cancer risk with OR (95% CI) of 1.13 (1.07-1.18) and a P-value of 4.63 * 10 - 8 The risk allele frequency for this SNP is zero in European-ancestry populations in 1000 Genomes Project and thus its association with breast cancer risk cannot be assessed in DRIVE GAME-ON Consortium. Functional annotation using the ENCODE data indicates that rs12118297 might be located in a repressed element and locus 21q22.12 may affect breast cancer risk through regulating LINC00160 expressions and interaction with oestrogen receptor signalling. Our findings provide additional insights into the genetics of breast cancer. PMID- 27354354 TI - Unravelling the nature of non-specific effects of vaccines-A challenge for innate immunologists. AB - Epidemiological observations have shown that vaccines can influence morbidity and mortality more than can be ascribed to target-disease immunity. A growing number of immunological studies have helped identify possible biological mechanisms to explain these so-called nonspecific effects (NSE) of vaccines, including heterologous T-cell reactivity and innate immune memory or 'trained innate immunity', which involves epigenetic reprogramming of innate immune cells. Here, we review the epidemiological evidence for NSE as well as human, animal and in vitro immunological data that could explain these NSE, and discuss priorities for future epidemiologic and immunologic studies to further unravel the biology and optimize the benefits of current and new vaccines. PMID- 27354356 TI - EETs and HO-1 cross-talk. AB - Epoxygenase-dependent metabolites of arachidonc acid, EETs and the heme-oxygenase (HO)-1/carbon monoxide/bilverdin system share similarities in their activity and mediators. They control endothelial function, dilating small arterial vessels, decrease blood pressure, protect the heart from ischemic and hypertensive cardiopathy, control renal circulation and function, promote angiogenesis and organ regeneration, oppose oxidative stress and inflammation, improve diabetes and obesity, have protective effects on the liver, and participate in portal hypertension. Furthermore, EETs induce HO-1, and inhibition of HO-1 abolishes most of the effects of EETs. Thus, a close interaction between the two systems exists, and is relevant in view of their therapeutic potential. PMID- 27354358 TI - Inner Workings: Will hagfish yield the fibers of the future? PMID- 27354359 TI - Core Concept: Basket trial approach capitalizes on the molecular mechanisms of tumors. PMID- 27354361 TI - Quantitative EEG Neurometric Analysis-Guided Neurofeedback Treatment in Postconcussion Syndrome (PCS): Forty Cases. How Is Neurometric Analysis Important for the Treatment of PCS and as a Biomarker? AB - Postconcussion syndrome (PCS) has been used to describe a range of residual symptoms that persist 12 months or more after the injury, often despite a lack of evidence of brain abnormalities on magnetic resonance imaging and computed tomography scans. In this clinical case series, the efficacy of quantitative EEG guided neurofeedback in 40 subjects diagnosed with PCS was investigated. Overall improvement was seen in all the primary (Symptom Assessment-45 Questionnaire, Clinical Global Impressions Scale, Hamilton Depression Scale) and secondary measures (Minnesota Multiphasic Personality Inventory, Test of Variables for Attention). The Neuroguide Traumatic Brain Index for the group also showed a decrease. Thirty-nine subjects were followed up long term with an average follow up length of 3.1 years (CI = 2.7-3.3). All but 2 subjects were stable and were off medication. Overall neurofeedback treatment was shown to be effective in this group of subjects studied. PMID- 27354362 TI - Family Perspectives on Whiteboard Use and Recommendations for Improved Practices. AB - OBJECTIVES: To explore pediatric family perspectives and preferences regarding whiteboard use, as well as recommendations for using whiteboards as tools for patient-centered communication and care. METHODS: Semi-structured interviews were conducted with 29 families in a pediatric urban academic hospital inpatient surgical service, exploring whiteboard experiences and suggestions. Parent responses were manually recorded during interviews. Quantitative data were analyzed by using descriptive statistics. RESULTS: Of all families, 66% reported using the whiteboard, and 52% were informed about it by staff. Among users, parents who were informed of the whiteboard used it actively (writing to share information) 6 times more often than those who used it passively (as a visual reference). Pictorial whiteboard analysis found that 42% of whiteboards had parent writing. Of these, 80% had contact information alone. Among reasons for whiteboard nonuse, 58% were modifiable, including not knowing about it, assuming it was intended for staff, believing no one would read it, or physical inaccessibility. Parents overwhelmingly identified nurses as whiteboard users (81%) compared with physicians (who families did not identify as users). The majority (76%) of families offered recommendations to improve whiteboard effectiveness. CONCLUSIONS: Of all families, approximately one-half were not informed about whiteboards and one-third did not use them. Reasons for nonuse were largely modifiable. Parents made aware of their whiteboard by their care teams demonstrated increased likelihood of active whiteboard use, highlighting the importance of education and suggesting a gap in harnessing the full potential of whiteboards as communication tools. Families' recommendations can help inform whiteboard practices to strengthen communication and care. PMID- 27354363 TI - Appendiceal orifice inflammation is associated with proximal extension of disease in patients with ulcerative colitis. AB - AIM: Ulcerative colitis (UC) is considered to be a disease of continuous mucosal inflammation extending proximally from the rectum. However, appendiceal orifice inflammation (AOI) is a skip lesion with segments of continuous involvement from the rectum. The aim of this study was to examine the clinical characteristics and clinical course, particularly focused on proximal extension, of UC in patients with AOI. METHOD: A retrospective evaluation of patients with UC who underwent total colonoscopy at the Department of Surgical Oncology, The University of Tokyo, from 2004 to 2014. The degree of AOI was graded endoscopically as follows: 0 (no inflammation); 1 (slight oedema); 2 (moderate inflammation); and 3 (marked inflammation). A total of 189 patient records were reviewed retrospectively. The presence of AOI was analysed with regard to the clinical information of each patient, and its association with proximal extension of proctitis or left-sided colitis was evaluated. RESULTS: Of 189 patients with UC who underwent total colonoscopy at our institution, 92 were diagnosed with pancolitis, 50 with left sided colitis and 47 with proctitis. Endoscopic findings of AOI were observed in 26 patients, including 11 (12.0%) with pancolitis, six (12.0%) with left-sided colitis and nine (19.1%) with proctitis. During follow up, proximal extension of the disease occurred in all nine patients with proctitis AOI. CONCLUSION: AOI is more frequently observed in patients with proctitis. Our results showed correlations between AOI and subsequent proximal extension of mucosal inflammation in patients with proctitis. PMID- 27354364 TI - A PBX1 transcriptional network controls dopaminergic neuron development and is impaired in Parkinson's disease. AB - Pre-B-cell leukemia homeobox (PBX) transcription factors are known to regulate organogenesis, but their molecular targets and function in midbrain dopaminergic neurons (mDAn) as well as their role in neurodegenerative diseases are unknown. Here, we show that PBX1 controls a novel transcriptional network required for mDAn specification and survival, which is sufficient to generate mDAn from human stem cells. Mechanistically, PBX1 plays a dual role in transcription by directly repressing or activating genes, such as Onecut2 to inhibit lateral fates during embryogenesis, Pitx3 to promote mDAn development, and Nfe2l1 to protect from oxidative stress. Notably, PBX1 and NFE2L1 levels are severely reduced in dopaminergic neurons of the substantia nigra of Parkinson's disease (PD) patients and decreased NFE2L1 levels increases damage by oxidative stress in human midbrain cells. Thus, our results reveal novel roles for PBX1 and its transcriptional network in mDAn development and PD, opening the door for new therapeutic interventions. PMID- 27354366 TI - Plasma Soluble CD163 Level Independently Predicts All-Cause Mortality in HIV-1 Infected Individuals. AB - BACKGROUND: CD163, a monocyte- and macrophage-specific scavenger receptor, is shed as soluble CD163 (sCD163) during the proinflammatory response. Here, we assessed the association between plasma sCD163 levels and progression to AIDS and all-cause mortality among individuals infected with human immunodeficiency virus type 1 (HIV). METHODS: Plasma sCD163 levels were measured in 933 HIV-infected individuals. Hazard ratios (HRs) with 95% confidence intervals (CIs) associated with mortality were computed by Cox proportional hazards regression. RESULTS: At baseline, 86% were receiving antiretroviral treatment, 73% had plasma a HIV RNA level of <50 copies/mL, and the median CD4(+) T-cell count was 503 cells/uL. During 10.5 years of follow-up, 167 (17.9%) died. Plasma sCD163 levels were higher in nonsurvivors than in survivors (4.92 mg/L [interquartile range {IQR}, 3.29-8.65 mg/L] vs 3.16 mg/L [IQR, 2.16-4.64 mg/L]; P = .0001). The cumulative incidence of death increased with increasing plasma sCD163 levels, corresponding to a 6% or 35% increased risk of death for each milligram per liter or quartile increase, respectively, in baseline plasma sCD163 level (adjusted HR, 1.06 [95% CI, 1.03-1.09] and 1.35 [95% CI, 1.13-1.63], respectively). CONCLUSIONS: Plasma sCD163 was an independent marker of all-cause mortality in a cohort of HIV infected individuals, suggesting that monocyte/macrophage activation may play a role in HIV pathogenesis and be a target of intervention. PMID- 27354365 TI - Generation and Protective Ability of Influenza Virus-Specific Antibody-Dependent Cellular Cytotoxicity in Humans Elicited by Vaccination, Natural Infection, and Experimental Challenge. AB - BACKGROUND: Nonneutralizing antibodies (Abs) involved in antibody-dependent cellular cytotoxicity (ADCC) may provide some protection from influenza virus infection. The ability of influenza vaccines to induce ADCC-mediating Abs (ADCC Abs) in adults and children is unclear. METHODS: We quantified ADCC-Abs in serum samples from adults who received a dose of inactivated subunit vaccine (ISV) targeting monovalent 2009 pandemic influenza A(H1N1) virus or live-attenuated influenza vaccine (LAIV) or who had laboratory-confirmed influenza A(H1N1) virus infection. We also measured ADCC-Abs in children who either received a dose of trivalent seasonal ISV followed by trivalent seasonal LAIV or 2 doses of LAIV. Finally, we assessed the ability of low and high ADCC-Ab titers to protect adults from experimental challenge with influenza A/Wisconsin/67/131/2005(H3N2) virus. RESULTS: Adults and children who received a dose of ISV had a robust increase in ADCC-Ab titers to both recombinant hemagglutinin (rHA) protein and homologous virus-infected cells. There was no detectable increase in titers of ADCC-Abs to rHA or virus-infected cells in adults and children who received LAIV. Higher titers (>=320) of preexisting ADCC-Abs were associated with lower virus replication and a significant reduction in total symptom scores in experimentally infected adults. CONCLUSIONS: ADCC-Ab titers increased following experimental influenza virus infection in adults and after ISV administration in both children and adults. PMID- 27354367 TI - Changes in Markers of T-Cell Senescence and Exhaustion With Atazanavir-, Raltegravir-, and Darunavir-Based Initial Antiviral Therapy: ACTG 5260s. AB - It is unclear whether differential roles of CD4(+) versus CD8(+) T-cell senescence/exhaustion and effects of antiretroviral therapy (ART) on these processes may contribute to morbidity in treated human immunodeficiency virus type 1 (HIV) infection. In a prospective 96-week trial, 328 HIV-infected ART naive participants were randomly assigned to receive tenofovir-emtricitabine plus either atazanavir/ritonavir, darunavir/ritonavir, or raltegravir. Markers of CD4(+) T-cell senescence (ie, the percentage of CD28(-)CD57(+) cells among CD4(+) T cells ) and CD4(+)/CD8(+) T-cell exhaustion (ie, the percentage of PD-1(+) cells among CD4(+)/CD8(+) T cells) decreased after ART. There were no changes in markers of CD8(+) T-cell senescence after ART and no differential changes in all markers in ART groups. Senescent CD4(+) and CD8(+) T cells may have differential roles in HIV pathogenesis. PMID- 27354369 TI - Soluble CD163 and Clinical Outcomes in Treated HIV Infection: Insights Into Mechanisms. PMID- 27354368 TI - Rapid Responses to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: A Randomized Controlled Trial. AB - BACKGROUND: Noroviruses pose a significant public health risk, particularly in very young individuals, older adults, and individuals with underlying conditions. We assessed 2 bivalent norovirus virus-like particle (VLP) vaccine candidate formulations in healthy adults aged 18-49 years. METHODS: Enrolled subjects (n = 454) randomly assigned among 3 groups received intramuscular placebo (saline) or vaccines containing either 15 ug or 50 ug of GI.1 VLP and 50 ug GII.4 VLP (15/50 and 50/50 formulations) adjuvanted with monophosphoryl lipid A and Al(OH)3 We present safety and immunogenicity assessments up to 28 days after vaccination. RESULTS: No vaccine-related serious adverse events or adverse events of special interest were reported. Reactions were mainly mild to moderate, the most frequent being transient pain, in 8%, 64%, and 73% of placebo, 15/50, and 50/50 groups, respectively; transient myalgia, headache, and fatigue were the commonest systemic adverse events. Subjects assessed per protocol (n = 442) displayed rapid immune responses to vaccination, peaking by days 7-10 and persisting through day 28. GI.1 responses were highest with the 50/50 formulation, but GII.4 responses were higher with the 15/50 formulation. CONCLUSIONS: Both candidate VLP vaccines were well tolerated and elicited robust immune responses by 7-10 days that persisted through day 28. The 15/50 formulation displayed the best balance of tolerability and immunogenicity. CLINICAL TRIALS REGISTRATION: NCT02142504. PMID- 27354370 TI - The Evolution and Transmission of Epidemic GII.17 Noroviruses. AB - BACKGROUND: In recent decades, the GII.4 norovirus genotype has predominated in epidemics worldwide and been associated with an increased rate of evolutionary change. In 2014, a novel GII.17 variant emerged and persisted, causing large outbreaks of gastroenteritis in China and sporadic infections globally. The origin, evolution, and transmission history of this new variant are largely unknown. METHODS: We generated 103 full capsid and 8 whole-genome sequences of GII.17 strains collected between August 2013 and November 2015 in Guangdong, China. Phylogenetic analyses were performed by integrating our data with those for all publically available GII.17 sequences. RESULTS: The novel emergent lineage GII.17_Kawasaki_2014 most likely originated from Africa around 2001 and evolved at a rate of 5.6 * 10(-3) substitutions/site/year. Within this lineage, a new variant containing several important amino acid changes emerged around August 2013 and caused extensive epidemics in 2014-2015. The phylodynamic and epidemic history of the GII.17_Kawasaki lineage shows similarities with the pattern observed for GII.4 norovirus evolution. Virus movements from Hong Kong to neighboring coastal cities were frequently observed. CONCLUSIONS: Our results provide new insights into GII.17 norovirus evolution and transmission and highlight the potential for a rare norovirus genotype to rapidly replace existing strains and cause local epidemics. PMID- 27354371 TI - The Domestic Ferret (Mustela putorius furo) as a Lethal Infection Model for 3 Species of Ebolavirus. AB - Small-animal models have been developed for several Filoviridae species; however, serial adaptation was required to produce lethal infection. These adapted viruses have sequence changes in several genes, including those that modulate the host immune response. Nonhuman primate models do not require adaptation of filoviruses. Here, we describe lethal models of disease for Bundibugyo, Sudan, and Zaire species of Ebolavirus in the domestic ferret, using wild-type nonadapted viruses. Pathologic features were consistent with disease in primates. Of particular importance, this is the only known small-animal model developed for Bundibugyo and the only uniformly lethal animal model for Bundibugyo. PMID- 27354372 TI - Broad and Temperature Independent Replication Potential of Filoviruses on Cells Derived From Old and New World Bat Species. AB - Filoviruses are strongly associated with several species of bats as their natural reservoirs. In this study, we determined the replication potential of all filovirus species: Marburg marburgvirus, Tai Forest ebolavirus, Reston ebolavirus, Sudan ebolavirus, Zaire ebolavirus, and Bundibugyo ebolavirus. Filovirus replication was supported by all cell lines derived from 6 Old and New World bat species: the hammer-headed fruit bat, Buettikofer's epauletted fruit bat, the Egyptian fruit bat, the Jamaican fruit bat, the Mexican free-tailed bat and the big brown bat. In addition, we showed that Marburg virus Angola and Ebola virus Makona-WPGC07 efficiently replicated at 37 degrees C, 37 degrees -41 degrees C, or 41 degrees C, contrary to the hypothesis that temporal elevation in temperature due to flight affects filovirus replication in bats. PMID- 27354373 TI - How a Fully Automated eHealth Program Simulates Three Therapeutic Processes: A Case Study. AB - BACKGROUND: eHealth programs may be better understood by breaking down the components of one particular program and discussing its potential for interactivity and tailoring in regard to concepts from face-to-face counseling. In the search for the efficacious elements within eHealth programs, it is important to understand how a program using lapse management may simultaneously support working alliance, internalization of motivation, and behavior maintenance. These processes have been applied to fully automated eHealth programs individually. However, given their significance in face-to-face counseling, it may be important to simulate the processes simultaneously in interactive, tailored programs. OBJECTIVE: We propose a theoretical model for how fully automated behavior change eHealth programs may be more effective by simulating a therapist's support of a working alliance, internalization of motivation, and managing lapses. METHODS: We show how the model is derived from theory and its application to Endre, a fully automated smoking cessation program that engages the user in several "counseling sessions" about quitting. A descriptive case study based on tools from the intervention mapping protocol shows how each therapeutic process is simulated. RESULTS: The program supports the user's working alliance through alliance factors, the nonembodied relational agent Endre and computerized motivational interviewing. Computerized motivational interviewing also supports internalized motivation to quit, whereas a lapse management component responds to lapses. The description operationalizes working alliance, internalization of motivation, and managing lapses, in terms of eHealth support of smoking cessation. CONCLUSIONS: A program may simulate working alliance, internalization of motivation, and lapse management through interactivity and individual tailoring, potentially making fully automated eHealth behavior change programs more effective. PMID- 27354374 TI - Exosomes mediate cell contact-independent ephrin-Eph signaling during axon guidance. AB - The cellular release of membranous vesicles known as extracellular vesicles (EVs) or exosomes represents a novel mode of intercellular communication. Eph receptor tyrosine kinases and their membrane-tethered ephrin ligands have very important roles in such biologically diverse processes as neuronal development, plasticity, and pathological diseases. Until now, it was thought that ephrin-Eph signaling requires direct cell contact. Although the biological functions of ephrin-Eph signaling are well understood, our mechanistic understanding remains modest. Here we report the release of EVs containing Ephs and ephrins by different cell types, a process requiring endosomal sorting complex required for transport (ESCRT) activity and regulated by neuronal activity. Treatment of cells with purified EphB2(+) EVs induces ephrinB1 reverse signaling and causes neuronal axon repulsion. These results indicate a novel mechanism of ephrin-Eph signaling independent of direct cell contact and proteolytic cleavage and suggest the participation of EphB2(+) EVs in neural development and synapse physiology. PMID- 27354376 TI - Mitochondrial lipid transport and biosynthesis: A complex balance. AB - Little is known about how mitochondrial lipids reach inner membrane-localized metabolic enzymes for phosphatidylethanolamine synthesis. Aaltonen et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201602007) and Miyata et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201601082) now report roles for two mitochondrial complexes, Ups2-Mdm35 and mitochondrial contact site and cristae organizing system, in the biosynthesis and transport of mitochondrial lipids. PMID- 27354375 TI - A Presenilin-2-ARF4 trafficking axis modulates Notch signaling during epidermal differentiation. AB - How primary cilia impact epidermal growth and differentiation during embryogenesis is poorly understood. Here, we show that during skin development, Notch signaling occurs within the ciliated, differentiating cells of the first few suprabasal epidermal layers. Moreover, both Notch signaling and cilia disappear in the upper layers, where key ciliary proteins distribute to cell-cell borders. Extending this correlation, we find that Presenilin-2 localizes to basal bodies/cilia through a conserved VxPx motif. When this motif is mutated, a GFP tagged Presenilin-2 still localizes to intercellular borders, but basal body localization is lost. Notably, in contrast to wild type, this mutant fails to rescue epidermal differentiation defects seen upon Psen1 and 2 knockdown. Screening components implicated in ciliary targeting and polarized exocytosis, we provide evidence that the small GTPase ARF4 is required for Presenilin basal body localization, Notch signaling, and subsequent epidermal differentiation. Collectively, our findings raise the possibility that ARF4-dependent polarized exocytosis acts through the basal body-ciliary complex to spatially regulate Notch signaling during epidermal differentiation. PMID- 27354377 TI - Exosomes expand the sphere of influence of Eph receptors and ephrins. AB - Membrane-anchored Eph receptors and ephrins represent a ubiquitous intercellular communication system that typically engages at sites of cell-cell contact to initiate bidirectional signaling. Gong et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201601085) show that cells can deploy the EphB2 receptor on exosomes to activate ephrinB signaling and collapse the growth cones of distant neurons. PMID- 27354379 TI - Phosphatidylserine transport by Ups2-Mdm35 in respiration-active mitochondria. AB - Phosphatidylethanolamine (PE) is an essential phospholipid for mitochondrial functions and is synthesized mainly by phosphatidylserine (PS) decarboxylase at the mitochondrial inner membrane. In Saccharomyces cerevisiae, PS is synthesized in the endoplasmic reticulum (ER), such that mitochondrial PE synthesis requires PS transport from the ER to the mitochondrial inner membrane. Here, we provide evidence that Ups2-Mdm35, a protein complex localized at the mitochondrial intermembrane space, mediates PS transport for PE synthesis in respiration-active mitochondria. UPS2- and MDM35-null mutations greatly attenuated conversion of PS to PE in yeast cells growing logarithmically under nonfermentable conditions, but not fermentable conditions. A recombinant Ups2-Mdm35 fusion protein exhibited phospholipid-transfer activity between liposomes in vitro. Furthermore, UPS2 expression was elevated under nonfermentable conditions and at the diauxic shift, the metabolic transition from glycolysis to oxidative phosphorylation. These results demonstrate that Ups2-Mdm35 functions as a PS transfer protein and enhances mitochondrial PE synthesis in response to the cellular metabolic state. PMID- 27354378 TI - SEC16A is a RAB10 effector required for insulin-stimulated GLUT4 trafficking in adipocytes. AB - RAB10 is a regulator of insulin-stimulated translocation of the GLUT4 glucose transporter to the plasma membrane (PM) of adipocytes, which is essential for whole-body glucose homeostasis. We establish SEC16A as a novel RAB10 effector in this process. Colocalization of SEC16A with RAB10 is augmented by insulin stimulation, and SEC16A knockdown attenuates insulin-induced GLUT4 translocation, phenocopying RAB10 knockdown. We show that SEC16A and RAB10 promote insulin stimulated mobilization of GLUT4 from a perinuclear recycling endosome/TGN compartment. We propose RAB10-SEC16A functions to accelerate formation of the vesicles that ferry GLUT4 to the PM during insulin stimulation. Because GLUT4 continually cycles between the PM and intracellular compartments, the maintenance of elevated cell-surface GLUT4 in the presence of insulin requires accelerated biogenesis of the specialized GLUT4 transport vesicles. The function of SEC16A in GLUT4 trafficking is independent of its previously characterized activity in ER exit site formation and therefore independent of canonical COPII-coated vesicle function. However, our data support a role for SEC23A, but not the other COPII components SEC13, SEC23B, and SEC31, in the insulin stimulation of GLUT4 trafficking, suggesting that vesicles derived from subcomplexes of COPII coat proteins have a role in the specialized trafficking of GLUT4. PMID- 27354380 TI - Genetic variations in the 3'-untranslated region of SLC18A2 are associated with serum FSH concentration in polycystic ovary syndrome patients and regulate gene expression in vitro. AB - STUDY QUESTION: Are genetic variations at the human solute carrier family 18 member A2 (SLC18A2) locus associated with the etiology of polycystic ovary syndrome (PCOS) and/or with follicle stimulating hormone (FSH) levels and insulin secretion in PCOS? SUMMARY ANSWER: We found two common genetic variants in the 3' untranslated region of SLC18A2 (rs363282 and rs363238) that are associated with serum FSH concentration in the PCOS group. WHAT IS KNOWN ALREADY: SLC18A2 is a vesicular monoamine transporter that is essential in dopamine regulation. Dopamine can negatively regulate FSH and insulin secretion through the D2 receptor. STUDY DESIGN, SIZE, DURATION: This study was a cross-sectional examination in women with PCOS (n = 319) and controls (n = 220) from China. PARTICIPANTS/MATERIALS, SETTING, METHODS: The PCOS patients were diagnosed based on the criteria of the Androgen Excess Society, including clinical and/or biochemical signs of hyperandrogenemia plus oligoamenorrhea or polycystic ovaries. Controls had regular menstrual cycles and no hyperandrogenism or other endocrine disorders related to PCOS. Tag single nucleotide polymorphisms (SNPs) were selected based on resequencing data in 48 PCOS patients and linkage disequilibrium analysis. Allele frequencies for variants (rs363282 and rs363238) were examined in PCOS cases and controls along with their relationship to quantitative traits. The samples were further divided into two subgroups for association analysis: AA + AG group and GG group (rs363282), CC + AC group and AA group (rs363238). The functional effects of SLC18A2 variants were measured by luciferase assay. The gene expression of SLC18A2 was compared with the NCBI's Gene Expression Omnibus datasets. MAIN RESULTS AND THE ROLE OF CHANCE: Two common genetic variants in the 3'-untranslated region (rs363282 and rs363238) are associated with serum FSH in the PCOS group (P= 0.005 and P= 0.001, respectively), while no associations were found in controls. Functional studies showed that minor alleles of the two variants (rs363282-G and rs363238-A) had significantly lower luciferase activities than rs363282-A (P= 0.009) and rs363238 C (P = 0.009). LIMITATIONS, REASONS FOR CAUTION: Results were not validated in another independent cohort, though we provided functional evidence of the two SNPs. Because of limited condition, more specific parameters, including ovarian follicle count and anti-Mullerian hormone were not included and relationship between SLC18A2 and these parameters cannot be evaluated. WIDER IMPLICATIONS OF THE FINDINGS: We found a novel association between two genetic variants in SLC18A2 and FSH levels in PCOS patients. These findings might indicate a novel regulatory mechanism in follicular development and maturation in PCOS. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Natural Science Foundation of China (grant numbers 81571501 and 81270747), National Basic Research Program of China (grant number 2015CB943300). No competing interests declared. PMID- 27354381 TI - Immuno-PET Imaging of Engineered Human T Cells in Tumors. AB - Sensitive in vivo imaging technologies applicable to the clinical setting are still lacking for adoptive T-cell-based immunotherapies, an important gap to fill if mechanisms of tumor rejection or escape are to be understood. Here, we propose a highly sensitive imaging technology to track human TCR-transgenic T cells in vivo by directly targeting the murinized constant TCR beta domain (TCRmu) with a zirconium-89 ((89)Zr)-labeled anti-TCRmu-F(ab')2 fragment. Binding of the labeled or unlabeled F(ab')2 fragment did not impair functionality of transgenic T cells in vitro and in vivo Using a murine xenograft model of human myeloid sarcoma, we monitored by Immuno-PET imaging human central memory T cells (TCM), which were transgenic for a myeloid peroxidase (MPO)-specific TCR. Diverse T-cell distribution patterns were detected by PET/CT imaging, depending on the tumor size and rejection phase. Results were confirmed by IHC and semiquantitative evaluation of T-cell infiltration within the tumor corresponding to the PET/CT images. Overall, these findings offer a preclinical proof of concept for an imaging approach that is readily tractable for clinical translation. Cancer Res; 76(14); 4113-23. (c)2016 AACR. PMID- 27354382 TI - Non-invasive high-frequency oscillatory ventilation in neonates: review of physiology, biology and clinical data. AB - Non-invasive high-frequency oscillatory ventilation (NHFOV) consists of the application of a bias flow generating a continuous distending positive pressure with superimposed oscillations, which have constant frequency and active expiratory phase. NHFOV matches together the advantages of high-frequency ventilation (no need for synchronisation, high efficacy in removing CO2) and nasal continuous positive airway pressure (CPAP) (non-invasive interface, increase in functional residual capacity allowing oxygenation to improve). There is enough clinical expertise demonstrating that NHFOV may be tried in some selected cases, in whom CPAP or conventional non-invasive ventilation have failed. Nonetheless, there are no clear data about its clinical usefulness and there is a need for randomised controlled studies. Our purpose is to review the physiology and biological effects of NHFOV, to present the current clinical evidence on its use, to provide some guiding principles to clinicians and suggest directions for further research. PMID- 27354383 TI - Changes in fetal autopsy patterns over a 10-year period. PMID- 27354384 TI - Undergraduate teaching of forensic medicine in Saudi Arabia. AB - Medico-legal tasks are not exclusive to forensic medical experts -any physician may face medico-legal issues in his career. Hence, the practice of medicine requires education in legal issues. In Saudi Arabia, there are 30 universities with medical colleges, but we do not know how they teach undergraduate forensic medicine and medico-legal issues. The aim of this study was to discover undergraduate training courses in forensic medicine in Saudi universities. We conducted a cross-sectional study involving all colleges of medicine in Saudi Arabia. A structured, self-administered questionnaire containing 13 items relating to the undergraduate forensic medicine course was distributed. Out of a total of 30 universities, 27 universities responded. Of these 27 universities, 16 (59.26%) teach forensic medicine to undergraduate medical students, and 11 (40.74%) do not teach forensic medicine in their undergraduate curriculum. Of the 27 universities that responded, none has a department of forensic medicine. Eleven universities that do not teach forensic medicine have no forensic medicine unit/division or faculty at all. Forensic medicine belongs to the pathology department in 11 universities, while it belongs to different departments in five universities. There is variation in teaching methods, years where the course is taught and length of the course. Practical and morgue visits take place in 7/16 (43.8%) universities, while 9/16 (56.3%) universities only teach the theoretical aspects of forensic medicine. All 16 universities teach forensic medicine only to medical students and do not teach it to students in other colleges such as dentistry and nursing. PMID- 27354385 TI - Response to letter from Steven B Karch re: "Excited delirium: a psychiatric review". PMID- 27354386 TI - Unpacking the Black Box of Wilderness Therapy: A Realist Synthesis. AB - Despite considerable progress within wilderness and adventure therapy research over the last decade, researchers are still unable to precisely answer why, how, and for whom this treatment modality works. There is also a need for more knowledge regarding the circumstances under which the treatment does not appear to be effective. In this realist synthesis, we attempt to unpack this "black box" of wilderness therapy more specifically, defined as a specialized approach to mental health treatment for adolescents. Through a focused review of the primary qualitative wilderness therapy studies, empirical findings are used to test and refine a key program theory. The synthesis results in a proposed wilderness therapy clinical model and offers informed implications for future theory development, research, and practice. PMID- 27354387 TI - Crafting Stories in Hermeneutic Phenomenology Research: A Methodological Device. AB - Hermeneutic phenomenology, as a methodology, is not fixed. Inherent in its enactment are contested areas of practice such as how interview data are used and reported. Using philosophical notions drawn from hermeneutic phenomenological literature, we argue that working with crafted stories is congruent with the philosophical underpinnings of this methodology. We consider how the practical ontic undertaking of story crafting from verbatim transcripts is integral with the interpretive process. We show how verbatim transcripts can be crafted into stories through examples taken from interview data. Our aim is to open dialogue with other hermeneutic phenomenological researchers and offer alternate possibilities to conventional ways of work with qualitative data. We argue that crafted stories can provide glimpses of phenomena that other forms of data analysis and presentation may leave hidden. We contend that crafted stories are an acceptable and trustworthy methodological device. PMID- 27354388 TI - Matching Evaluation Approaches to Levels of Complexity. AB - BACKGROUND: Despite rapid advances in research on the evaluation of complex interventions, debate on evaluation methods and approaches still mainly revolves around the conventional and mostly outdated positivist-constructivist dichotomy. The lack of a clear conceptual and theoretical framework from which to choose appropriate evaluation approaches and methods means that approaches are often misused by both researchers and practitioners. RESEARCH DESIGN: Using three case studies, this article shows how different approaches should and should not be used in practice according to levels of nonlinearity. Both the theoretical development and the case studies presented in this article rely heavily on interviews conducted by the author with program management and staff, evaluation managers, heads of evaluation units, and evaluators in several countries across two continents, along with a quantitative survey. RESULTS: This article expands the classic discussion on evaluation approaches, adapting it to current managerial demands, increased complexity, and newly developed methodologies. It suggests an operational tool for categorizing evaluations and then matching evaluation approaches to the circumstances and the evaluation objectives. CONCLUSION: The findings suggest that approaches which are not congruent with levels of nonlinearity may hinder attempts to accurately evaluate results, causing dissatisfaction of evaluation commissioners from the evaluation process and methods applied. In contrast, analyzing the nonlinear and structural elements of complexity separately allows an extended categorization of evaluation approaches to be matched to the nonlinearity of programs to be evaluated. PMID- 27354389 TI - Academic and Behavioral Design Parameters for Cluster Randomized Trials in Kindergarten: An Analysis of the Early Childhood Longitudinal Study 2011 Kindergarten Cohort (ECLS-K 2011). AB - BACKGROUND: There is an increased focus on randomized trials for proximal behavioral outcomes in early childhood research. However, planning sample sizes for such designs requires extant information on the size of effect, variance decomposition, and effectiveness of covariates. OBJECTIVES: The purpose of this article is to employ a recent large representative sample of early childhood longitudinal study kindergartners to estimate design parameters for use in planning cluster randomized trials. A secondary objective is to compare the results of math and reading with the previous kindergartner cohort of 1999. RESEARCH DESIGN: For each measure, fall-spring gains in effect size units are calculated. In addition, multilevel models are fit to estimate variance components that are used to calculate intraclass correlations (ICCs) and R 2 statistics. The implications of the reported parameters are summarized in tables of required school sample sizes to detect small effects. MEASURES: The outcomes include information about student scores regarding learning behaviors, general behaviors, and academic abilities. RESULTS: Aside from math and reading, there were small gains in these measures from fall to spring, leading to effect sizes between about .1 and .2. In addition, the nonacademic ICCs are smaller than the academic ICCs but are still nontrivial. Use of a pretest covariate is generally effective in reducing the required sample size in power analyses. The ICCs for math and reading are smaller for the current sample compared with the 1999 sample. PMID- 27354392 TI - Ethics of Caring Conversation and Dialectic of Love and Justice. AB - Through the framework of Ricoeur's philosophy, Fredriksson and Eriksson develop an influential ethics of the caring conversation, which instructs nurses to have caritas, self-esteem, and autonomy on one hand and to engage respectfully and responsibly in caring conversations on the other. This article brings the ethics of the caring conversation into dialogue with Ricoeur's philosophy again. While Fredriksson and Eriksson draw upon Ricoeur's little ethics, this article relies on Ricoeur's dialectic of love and justice. The dialogue throws light on other aspects of caritas, which is vital in Fredriksson and Eriksson's ethics. It shows a need for nurses to strike a balance between love and justice and, also, to cultivate love. PMID- 27354390 TI - Defective glutamate and K+ clearance by cortical astrocytes in familial hemiplegic migraine type 2. AB - Migraine is a common disabling brain disorder. A subtype of migraine with aura (familial hemiplegic migraine type 2: FHM2) is caused by loss-of-function mutations in alpha2 Na(+),K(+) ATPase (alpha2 NKA), an isoform almost exclusively expressed in astrocytes in adult brain. Cortical spreading depression (CSD), the phenomenon that underlies migraine aura and activates migraine headache mechanisms, is facilitated in heterozygous FHM2-knockin mice with reduced expression of alpha2 NKA The mechanisms underlying an increased susceptibility to CSD in FHM2 are unknown. Here, we show reduced rates of glutamate and K(+) clearance by cortical astrocytes during neuronal activity and reduced density of GLT-1a glutamate transporters in cortical perisynaptic astrocytic processes in heterozygous FHM2-knockin mice, demonstrating key physiological roles of alpha2 NKA and supporting tight coupling with GLT-1a. Using ceftriaxone treatment of FHM2 mutants and partial inhibition of glutamate transporters in wild-type mice, we obtain evidence that defective glutamate clearance can account for most of the facilitation of CSD initiation in FHM2-knockin mice, pointing to excessive glutamatergic transmission as a key mechanism underlying the vulnerability to CSD ignition in migraine. PMID- 27354393 TI - YouTube(r): An ally or an enemy in the promotion of living donor kidney transplantation? AB - The aim of the study is to evaluate the availability and accuracy of the existing Italian-language medical information about living donor kidney transplantation on YouTube(r). For each video, several data were collected, and each video was classified as "useful," "moderately useful" and "not useful." Globally, the search resulted in 306 videos: 260 were excluded and 46 included in the analysis. The main message conveyed by the video was positive in 28 cases (60.9%), neutral in 16 (34.8%) and negative in 2 (4.4%). The mean amount of visualizations was 3103.5 (range: 17-90,133) and the mean amount of "likes" 2.7 (range: 0-28). Seven videos (15.2%) were classified as "useful," 21 (45.7%) as "moderately useful" and 18 (39.1%) as "not useful." This study showed that a very few videos in Italian about living donor kidney transplantation are available on YouTube, with only 15 percent of them containing useful information for the general population. PMID- 27354391 TI - Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRalpha1 domains. AB - Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding human endothelial protein C receptor (EPCR) through the CIDRalpha1 domain of certain PfEMP1 were recently associated with severe malaria in children. However, it has remained unclear to which extend the EPCR-binding CIDRalpha1 domains epitomize PfEMP1 expressed in severe malaria. Here, we characterized the near full-length transcripts dominating the var transcriptome in children with severe malaria and found that the only common feature of the encoded PfEMP1 was CIDRalpha1 domains. Such genes were highly and dominantly expressed in both children with severe malarial anaemia and cerebral malaria. These observations support the hypothesis that the CIDRalpha1-EPCR interaction is key to the pathogenesis of severe malaria and strengthen the rationale for pursuing a vaccine or adjunctive treatment aiming at inhibiting or reducing the damaging effects of this interaction. PMID- 27354394 TI - A randomized controlled pilot study of CBT-I Coach: Feasibility, acceptability, and potential impact of a mobile phone application for patients in cognitive behavioral therapy for insomnia. AB - There has been growing interest in utilizing mobile phone applications (apps) to enhance traditional psychotherapy. Previous research has suggested that apps may facilitate patients' completion of cognitive behavioral therapy for insomnia (CBT I) tasks and potentially increase adherence. This randomized clinical trial pilot study ( n = 18) sought to examine the feasibility, acceptability, and potential impact on adherence and sleep outcomes related to CBT-I Coach use. All participants were engaged in CBT-I, with one group receiving the app as a supplement and one non-app group. We found that patients consistently used the app as intended, particularly the sleep diary and reminder functions. They reported that it was highly acceptable to use. Importantly, the app did not compromise or undermine benefits of cognitive behavioral therapy for insomnia and patients in both groups had significantly improved sleep outcomes following treatment. PMID- 27354395 TI - Logic Learning Machine and standard supervised methods for Hodgkin's lymphoma prognosis using gene expression data and clinical variables. AB - This study evaluates the performance of a set of machine learning techniques in predicting the prognosis of Hodgkin's lymphoma using clinical factors and gene expression data. Analysed samples from 130 Hodgkin's lymphoma patients included a small set of clinical variables and more than 54,000 gene features. Machine learning classifiers included three black-box algorithms ( k-nearest neighbour, Artificial Neural Network, and Support Vector Machine) and two methods based on intelligible rules (Decision Tree and the innovative Logic Learning Machine method). Support Vector Machine clearly outperformed any of the other methods. Among the two rule-based algorithms, Logic Learning Machine performed better and identified a set of simple intelligible rules based on a combination of clinical variables and gene expressions. Decision Tree identified a non-coding gene ( XIST) involved in the early phases of X chromosome inactivation that was overexpressed in females and in non-relapsed patients. XIST expression might be responsible for the better prognosis of female Hodgkin's lymphoma patients. PMID- 27354396 TI - Strategies to improve effectiveness of physical activity coaching systems: Development of personas for providing tailored feedback. AB - Mobile physical activity interventions can be improved by incorporating behavioural change theories. Relations between self-efficacy, stage of change, and physical activity are investigated, enabling development of feedback strategies that can be used to improve their effectiveness. A total of 325 healthy control participants and 82 patients wore an activity monitor. Participants completed a self-efficacy or stage of change questionnaire. Results show that higher self-efficacy is related to higher activity levels. Patients are less active than healthy controls and show a larger drop in physical activity over the day. Patients in the maintenance stage of change are more active than patients in lower stages of change, but show an equally large drop in level of physical activity. Findings suggest that coaching should at least be tailored to level of self-efficacy, stage of change, and physical activity pattern. Tailored coaching strategies are developed, which suggest that increasing self-efficacy of users is most important. Guidelines are provided. PMID- 27354397 TI - Multisegment Foot Kinematic and Kinetic Compensations in Level and Uphill Walking Following Tibiotalar Arthrodesis. AB - BACKGROUND: Foot and ankle movement alterations following ankle arthrodesis are still not well understood, particularly those that might contribute to the documented increase in adjacent joint arthritis. Generalized tarsal hypermobility has long been postulated, but not confirmed in gait or functional movements. The purpose of this study was to more thoroughly evaluate compensation mechanisms used by arthrodesis patients during level and uphill gait through a variety of measurement modalities and a detailed breakdown of gait phases. METHODS: Level ground and uphill gait of 14 unilateral tibiotalar arthrodesis patients and 14 matched controls was analyzed using motion capture, force, and pressure measurements in conjunction with a kinetic multisegment foot model. RESULTS: The affected limb exhibited several marked differences compared to the controls and to the unaffected limb. In loading response, ankle eversion was reduced but without a reduction in tibial rotation. During the second rocker, ankle dorsiflexion was reduced, yet was still considerable, suggesting compensatory talar articulation (subtalar and talonavicular) motion since no differences were seen at the midtarsal joint. Also during the second rocker, subjects abnormally internally rotated the tibia while moving their center of pressure laterally. Third rocker plantarflexion motion, moments, and powers were substantially reduced on the affected side and to a lesser extent on the unaffected side. CONCLUSION: Sagittal plane hypermobility is probable during the second rocker in the talar articulations following tibiotalar fusion, but is unlikely in other midfoot joints. The normal coupling between frontal plane hindfoot motion and tibial rotation in early and mid stance was also clearly disrupted. These alterations reflect a complex compensatory movement pattern that undoubtedly affects the function of arthrodesis patients, likely alters the arthrokinematics of the talar joints (which may be a mechanism for arthritis development), and should be considered in future arthrodesis as well as arthroplasty research. LEVEL OF EVIDENCE: Level III, comparative study. PMID- 27354398 TI - Neuromuscular Impairments Are Associated With Impaired Head and Trunk Stability During Gait in Parkinson Fallers. AB - Background The trunk plays a critical role in attenuating movement-related forces that threaten to challenge the body's postural control system. For people with Parkinson's disease (PD), disease progression often leads to dopamine-resistant axial symptoms, which impair trunk control and increase falls risk. Objective This prospective study aimed to evaluate the relationship between impaired trunk muscle function, segmental coordination, and future falls in people with PD. Methods Seventy-nine PD patients and 82 age-matched controls completed clinical assessments and questionnaires to establish their medical history, symptom severity, balance confidence, and falls history. Gait characteristics and trunk muscle activity were assessed using 3-dimensional motion analysis and surface electromyography. The incidence, cause, and consequence of any falls experienced over the next 12 months were recorded and indicated that 48 PD and 29 control participants fell at least once during this time. Results PD fallers had greater peak and baseline lumbar multifidus (LMF) and thoracic erector spinae (TES) activations than control fallers and nonfallers. Analysis of covariance indicated that the higher LMF activity was attributable to the stooped posture adopted by PD fallers, but TES activity was independent of medication use, symptom severity, and trunk orientation. Furthermore, greater LMF and TES baseline activity contributed to increasing lateral head, trunk, and pelvis movements in PD fallers but not nonfallers or controls. Conclusions The results provide evidence of neuromuscular deficits for PD fallers that are independent of medications, symptom severity, and posture and contribute to impaired head, trunk, and pelvis control associated with falls in this population. PMID- 27354399 TI - Determining Measurement Error for Bohler's Angle and the Effect of X-Ray Obliquity on Accuracy. AB - BACKGROUND: Bohler's angle (BA) is the most commonly utilized radiographic measurement in the study of calcaneus fractures and has been shown to be prognostic in nature. Therefore, it is critical that the measurement of BA be accurate as both therapeutic and prognostic information relies on it. Oblique lateral radiographs can be a cause of error in BA measurements. However, measurement error and the effects of X-ray beam obliquity on BA have not been established in the literature. The purpose of this study was to determine measurement error and understand the effects of X-ray beam's obliquity on the measurement of BA. METHODS: A cadaver specimen was imaged using a C-arm to obtain a perfect lateral radiograph of the ankle and slightly oblique lateral views in the anterior, posterior, cephalad, and caudad directions in 5 degrees increments (21 images). Metallic beads were then placed on the anterior calcaneal process, posterior facet, and the superior aspect of the posterior tuberosity, and the same 21 images were then obtained. The metallic beads placed on the reference radiographs allowed the authors to accurately measure BA for each image and served as reference for the corresponding test radiographs. Thirty-four orthopaedic staff members participated in the study and used DICOM measurement tool to measure BA on each of the 21 test radiographs. The measurements were then compared to the measurements of BA from the reference radiographs to determine error in measurement. RESULTS: A total of 714 different measurements were obtained. Average measurement error was 6 degrees (95% confidence interval = -4 degrees to 15 degrees ). The difference between the observed BA measurements compared to the true BA measurements increased with increasing X-ray obliquity. CONCLUSIONS: Measurement error for BA is +/-6 degrees and increases most with cephalad oblique radiographs. Orthopaedic surgeons' ability to accurately measure BA significantly decreases with increasing obliquity of the lateral radiograph. LEVELS OF EVIDENCE: Level V: Cadaver bench study. PMID- 27354400 TI - Spatial Mapping of Pyocyanin in Pseudomonas Aeruginosa Bacterial Communities Using Surface Enhanced Raman Scattering. AB - Surface enhanced Raman spectroscopy (SERS) imaging was used in conjunction with principal component analysis (PCA) for the in situ spatiotemporal mapping of the virulence factor pyocyanin in communities of the pathogenic bacterium Pseudomonas aeruginosa. The combination of SERS imaging and PCA analysis provides a robust method for the characterization of heterogeneous biological systems while circumventing issues associated with interference from sample autofluorescence and low reproducibility of SERS signals. The production of pyocyanin is found to depend both on the growth carbon source and on the specific strain of P. aeruginosa studied. A cystic fibrosis lung isolate strain of P. aeruginosa synthesizes and secretes pyocyanin when grown with glucose and glutamate, while the laboratory strain exhibits detectable production of pyocyanin only when grown with glutamate as the source of carbon. Pyocyanin production in the laboratory strain grown with glucose was below the limit of detection of SERS. In addition, the combination of SERS imaging and PCA can elucidate subtle differences in the molecular composition of biofilms. PCA loading plots from the clinical isolate exhibit features corresponding to vibrational bands of carbohydrates, which represent the mucoid biofilm matrix specific to that isolate, features that are not seen in the PCA loading plots of the laboratory strain. PMID- 27354401 TI - Discriminating the Mineralogical Composition in Drill Cuttings Based on Absorption Spectra in the Terahertz Range. AB - Understanding the geological units of a reservoir is essential to the development and management of the resource. In this paper, drill cuttings from several depths from an oilfield were studied using terahertz time domain spectroscopy (THz-TDS). Cluster analysis (CA) and principal component analysis (PCA) were employed to classify and analyze the cuttings. The cuttings were clearly classified based on CA and PCA methods, and the results were in agreement with the lithology. Moreover, calcite and dolomite have stronger absorption of a THz pulse than any other minerals, based on an analysis of the PC1 scores. Quantitative analyses of minor minerals were also realized by building a series of linear and non-linear models between contents and PC2 scores. The results prove THz technology to be a promising means for determining reservoir lithology as well as other properties, which will be a significant supplementary method in oil fields. PMID- 27354402 TI - Valdecoxib Recovers the Lipid Composition, Order and Dynamics in Colon Cancer Cell Lines Independent of COX-2 Expression: An ATR-FTIR Spectroscopy Study. AB - Prostanoids play an important role in a variety of physiological and pathophysiological processes including inflammation and cancer. The rate-limiting step in the prostanoid biosynthesis pathway is catalyzed by cyclooxygenases (COXs). Aberrant expression of the inducible isoform COX-2 plays a significant role in colon cancer initiation and progression. In this study, we have hypothesized that COX-2 specific inhibitors such as Valdecoxib (VLX), being highly hydrophobic, may alter biophysical properties of cellular lipids. In this study, COX-2 expressing (HT29) and COX-2 non-expressing (SW620) colon cancer cell lines were treated with VLX and examined using attenuated total reflection infrared spectroscopy. The results revealed that VLX treatment decreased lipid fluidity in the cells irrespective of COX-2 expression status and affected order parameters of the lipids in both cell lines. Cluster analysis also indicated that the spectral differences between the two cell lines are profound and could be successfully differentiated. Valdecoxib treatment could enhance the composition, order and dynamics of the lipids of colon cancer cells independently of its COX-2 inhibitory mechanism. Valdecoxib has therapeutic effects upon colon cancer, therefore it can be used as an adjuvant and/or chemopreventive agent for colon cancer. PMID- 27354403 TI - Detection Limits for Blood on Fabrics Using Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy and Derivative Processing. AB - Attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR) was used to detect blood stains based on signature protein absorption in the mid IR region, where intensity changes in the spectrum can be related to blood concentration. Partial least squares regression (PLSR) was applied for multivariate calibrations of IR spectra of blood dilutions on four types of fabric (acrylic, nylon, polyester, and cotton). Gap derivatives (GDs) were applied as a preprocessing technique to optimize the performance of calibration models. We report a much improved IR detection limit (DL) for blood on cotton (2700* in dilution factor units) and the first IR DL reported for blood on nylon (250*). Due to sample heterogeneity caused by fabric hydrophobicity, acrylic fabric produced variable ATR FT-IR spectra that caused poor DLs in concentration units compared to previous work. Polyester showed a similar problem at low blood concentrations that lead to a relatively poor DL as well. However, the increased surface sensitivity and decreased penetration depth of ATR FT-IR make it an excellent choice for detection of small quantities of blood on the front surface of all fabrics tested (0.0010 ug for cotton, 0.0077 ug for nylon, 0.011 ug for acrylic, and 0.0066 ug for polyester). PMID- 27354404 TI - Fourier Transform Infrared Spectroscopy and Photoacoustic Spectroscopy for Saliva Analysis. AB - Saliva provides a valuable tool for assessing oral and systemic diseases, but concentrations of salivary components are very small, calling the need for precise analysis methods. In this work, Fourier transform infrared (FT-IR) spectroscopy using transmission and photoacoustic (PA) modes were compared for quantitative analysis of saliva. The performance of these techniques was compared with a calibration series. The linearity of spectrum output was verified by using albumin-thiocyanate (SCN(-)) solution at different SCN(-) concentrations. Saliva samples used as a comparison were obtained from healthy subjects. Saliva droplets of 15 uL were applied on the silicon sample substrate, 6 drops for each specimen, and dried at 37 C overnight. The measurements were carried out using an FT-IR spectrometer in conjunction with an accessory unit for PA measurements. The findings with both transmission and PA modes mirror each other. The major bands presented were 1500-1750 cm(-1) for proteins and 1050-1200 cm(-1) for carbohydrates. In addition, the distinct spectral band at 2050 cm(-1) derives from SCN(-) anions, which is converted by salivary peroxidases to hypothiocyanate (OSCN(-)). The correlation between the spectroscopic data with SCN(-) concentration (r > 0.990 for transmission and r = 0.967 for PA mode) was found to be significant (P < 0.01), thus promising to be utilized in future applications. PMID- 27354405 TI - Spectroscopic Investigation Leading to the Documentation of Three Post-Byzantine Wall Paintings. AB - The main churches of three monasteries in Thessalia, Central Greece, were decorated with wall paintings in the post-Byzantine period. The main goal of the present study is to characterize the inorganic and organic materials present in the paint layers of areas that have been gilded. Optical microscopic examination was carried out on samples taken from the gilded decoration of the paintings to view their layer build-up. The combined use of micro Fourier transform infrared (FT-IR) and micro-Raman spectroscopy led to the detection of the pigments and the binding media used. The results from specimens taken from different wall paintings were compared with each other to observe their differences and similarities. The three investigated churches are believed to have been painted by the same iconographer, Tzortzis, who however has only been identified in only one of them. The comparison led to the conclusion that there are many similarities in the painting materials used and the general methodology adopted and, therefore, this study offers support to the belief that the mural paintings of the three monasteries could have been painted by the same iconographer. While not authenticating the two painting as being by Tzortzis, the results provide further critical material that is consistent with this attribution. However, this statement must be carefully considered because the pigments identified have been commonly and diffusely used in historic mural paintings. PMID- 27354406 TI - The Calreticulin gene and myeloproliferative neoplasms. AB - The Philadelphia negative myeloproliferative neoplasms include polycythaemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). Patients with these conditions were mainly thought to harbour JAK2V617F mutations or an Myeloproliferative leukaemia (MPL) substitution. In 2013, two revolutionary studies identified recurrent mutations in a gene that encodes the protein calreticulin (CALR). This mutation was detected in patients with PMF and ET with non-mutated JAK2 or MPL but was absent in patients with PV. The CALR gene encodes the calreticulin protein, which is a multifactorial protein, mainly located in the endoplasmic reticulum in chromosome 19 and regulates calcium homeostasis, chaperones and has also been implicated in multiple cellular processes including cell signalling, regulation of gene expression, cell adhesion, autoimmunity and apoptosis. Somatic 52 bp deletions and recurrent 52 bp insertion mutations in CALR were detected and all resulted in frameshift and clusters in exon 9 of the gene. This review will summarise the current knowledge on the CALR gene and mutation of the gene in pathological conditions and patient phenotypes. PMID- 27354407 TI - AGEing heart valves: a bittersweet stiffening process? PMID- 27354408 TI - Specific phenotype and function of CD56-expressing innate immune cell subsets in human thymus. AB - Whereas innate immune cells, such as NK and innate lymphoid cells (ILCs), have been characterized in different human tissues, knowledge on the thymic CD56 expressing cell subsets is limited. In this study, the rare subpopulations of thymic CD56+CD3- cells from samples of >100 patients have been successfully analyzed. The results revealed fundamental differences between thymic and peripheral blood (PB) CD56+CD3- cells. Thymic tissues lacked immunoregulatory CD56highCD16dim NK cells but showed two Eomes+CD56dim subsets on which common NK cell markers were significantly altered. CD56dimCD16high cells expressed high amounts of NKG2A, NKG2D, and CD27 with low CD57. Conversely, CD56dimCD16dim cells displayed high CD127 but low expression of KIR, NKG2D, and natural cytotoxicity receptors (NCRs). Thymic CD56+CD3- cells were able to gain cytotoxicity but were especially immunoregulatory cells, producing a broad range of cytokines. Finally, one population of thymic CD56+ cells resembled conventional NK cells, whereas the other represented a novel, noncanonical NK subset. PMID- 27354410 TI - Monocyte CD163 is altered in association with diabetic complications: possible protective role. AB - The scavenger receptor CD163 is exclusively expressed by monocyte/macrophages and is shed by matrix metalloproteinases (MMPs) and neutrophil elastase (ELA2) as soluble CD163 (sCD163). Monocyte phenotype is altered in diabetes, but the relationship among monocyte CD163, sCD163, and diabetic complications is not known and was investigated in this study. Blood was obtained from patients with diabetes for >10 yr and mice with diabetes for <=20 wk. Blood from people and mice without diabetes acted as controls. The percentage of CD163+ monocytes and monocyte CD163 mRNA was determined by flow cytometry and qRT-PCR, respectively. Plasma sCD163, MMPs, and ELA2 were measured by ELISA. The ability of glucocorticoids to stimulate isolated monocyte CD163 expression was also investigated. The percentage of CD163+ monocytes was significantly decreased and sCD163 significantly increased (both P < 0.05) in patients with diabetes with complications compared to those without complications. Plasma ELA2 and MMP-3 were also increased (P < 0.05), but CD163 mRNA was unaltered. sCD163 correlated with worsening renal function, as determined by eGFR (r = -0.48, P < 0.05). In diabetic mice, increased sCD163 at wk 5 and decreased percentage of CD163+ monocytes at wk 10 preceded alteration in kidney collagen IV mRNA at wk 20 (all P < 0.05). In vitro incubation of monocytes in anti-inflammatory glucocorticoid increased the percentage of CD163+ monocytes (P < 0.05). In people, higher sCD163 and decreased percentage of CD163+ monocytes were consistent with increased monocyte activation and shedding. The murine data indicated that these changes preceded the development of diabetic complications. Taken together, these results suggest that higher circulating percentage of CD163+ monocytes may have anti inflammatory effects and may protect from development of diabetic complications. PMID- 27354409 TI - Protection of CD4+ T cells from hepatitis C virus infection-associated senescence via DeltaNp63-miR-181a-Sirt1 pathway. AB - T cell dysfunction has a crucial role in establishing and maintaining viral persistence. We have previously shown a decline in miR-181a, which regulates CD4+ T cell responses via DUSP6 overexpression, in individuals with hepatitis C virus (HCV) infection. Here, we describe accelerated T cell senescence in HCV-infected individuals compared with age- and sex-matched healthy subjects. Mechanistic studies revealed that up-regulation of transcription factor DeltaNp63 led to the decline of miR-181a expression, resulting in an overexpression of the antiaging protein Sirt1, in CD4+ T cells from HCV-infected individuals. Either reconstituting miR-181a or silencing DeltaNp63 or Sirt1 expression in CD4+ T cells led to accelerated T cell senescence, as evidenced by an increased senescence-associated beta-galactosidase (SA-beta-gal) expression, shortened telomere length, and decreased EdU incorporation; this suggests that HCV-induced T cell senescence is counterregulated by the DeltaNp63-miR-181a-Sirt1 pathway. An increase of IL-2 production was observed in these senescent CD4+ T cells and was driven by a markedly reduced frequency of Foxp3+ regulatory T (Treg) cells and increased number of Foxp3- effector T (Teff) cells upon manipulating the DeltaNp63-miR-181a-Sirt1 pathway. In conclusion, these findings provide novel mechanistic insights into how HCV uses cellular senescent pathways to regulate T cell functions, revealing new targets for rejuvenating impaired T cell responses during chronic viral infection. PMID- 27354411 TI - The role of MyD88- and TRIF-dependent signaling in monophosphoryl lipid A-induced expansion and recruitment of innate immunocytes. AB - Treatment with the TLR4 agonist MPLA augments innate resistance to common bacterial pathogens. However, the cellular and molecular mechanisms by which MPLA augments innate immunocyte functions are not well characterized. This study examined the importance of MyD88- and TRIF-dependent signaling for leukocyte mobilization, recruitment, and activation following administration of MPLA. MPLA potently induced MyD88- and TRIF-dependent signaling. A single injection of MPLA caused rapid mobilization and recruitment of neutrophils, a response that was largely mediated by the chemokines CXCL1 and -2 and the hemopoietic factor G-CSF. Rapid neutrophil recruitment and chemokine production were regulated by both pathways although the MyD88-dependent pathway showed some predominance. In further studies, multiple injections of MPLA potently induced mobilization and recruitment of neutrophils and monocytes. Neutrophil recruitment after multiple injections of MPLA was reliant on MyD88-dependent signaling, but effective monocyte recruitment required activation of both pathways. MPLA treatment induced expansion of myeloid progenitors in bone marrow and upregulation of CD11b and shedding of L-selectin by neutrophils, all of which were attenuated in MyD88- and TRIF-deficient mice. These results show that MPLA-induced neutrophil and monocyte recruitment, expansion of bone marrow progenitors and augmentation of neutrophil adhesion molecule expression are regulated by both the MyD88- and TRIF-dependent pathways. PMID- 27354412 TI - At The Bedside: Clinical review of chimeric antigen receptor (CAR) T cell therapy for B cell malignancies. AB - T cells kill microbial-infected and malignant cells by detection of nonself antigens with the TCR. Tumor reactivity can be encoded genetically by introducing a chimeric antigen receptor (CAR) into T cells. CARs are composed of an antigen binding domain and an intracellular T cell activation domain. Early human trials evaluating CD19-targeted CAR T cells for chronic lymphocytic leukemia (CLL) showed limited responses until CARs included a costimulation domain, and conditioning chemotherapy was given before T cell infusion. Clinical trials evaluating CD19-targeted CAR T cells for B cell acute lymphoblastic leukemia (B ALL) are demonstrating response rates up to 90%. However, these clinical outcomes are associated with a cytokine release syndrome (CRS), which is caused by T cell activation and manifests as high-grade fever, hypotension, and other cardiovascular complications. It is currently managed conservatively but can be treated with cytokine-directed therapy or with high-dose steroids. Current efforts are dedicated to confirming the clinical efficacy and managing toxicities in multicenter Phase II trials. We present a thorough overview of the preclinical and clinical development of CAR T cell therapy that will highlight important areas for the basic researcher to investigate in the laboratory and contribute to this exciting field. PMID- 27354414 TI - Tunable capacitive coupling between two semiconductor charge qubits. AB - Strong coupling between two qubits is one of the main requirements for high fidelity two-qubit logic operations. Here we experimentally investigate the capacitive coupling between two double quantum dots. A pair of open slot confinement gates is used to enhance the coupling. We find that the coupling energy J can be conveniently tuned in a broad range. Through numerical simulations, we study the effect of J on two-qubit operations. The analysis shows that our experimentally obtained J is adequate to achieve high fidelity two-qubit entanglement and logic gates. PMID- 27354415 TI - Substance misuse and sexual function in adolescents with chronic diseases. AB - OBJECTIVE: To evaluate alcohol/tobacco and/or illicit drug misuse in Chronic Diseases (CDs). METHODS: A cross-sectional study with 220 CDs adolescents and 110 healthy controls including: demographic/anthropometric data; puberty markers; modified questionnaire evaluating sexual function, alcohol/smoking/illicit drug misuse and bullying; and the physician-conducted CRAFFT (car/relax/alone/forget/friends/trouble) screen tool for substance abuse/dependence high risk. RESULTS: The frequencies of alcohol/tobacco and/or illicit drug use were similar in both groups (30% vs. 34%, p=0.529), likewise the frequencies of bullying (42% vs. 41%, p=0.905). Further analysis solely in CDs patients that used alcohol/tobacco/illicit drug versus those that did not use showed that the median current age [15 (11-18) vs. 14 (10-18) years, p<0.0001] and education years [9 (5-14) vs. 8 (3-12) years, p<0.0001] were significant higher in substance use group. The frequencies of Tanner 5 (p<0.0001), menarche (p<0.0001) and spermarche (p=0.001) were also significantly higher in patients with CDs that used alcohol/tobacco/illicit, likewise sexual activity (23% vs. 3%, p<0.0001). A trend of a low frequency of drug therapy was observed in patients that used substances (70% vs. 82%, p=0.051). A positive correlation was observed between CRAFFT score and current age in CD patients (p=0.005, r=+0.189) and controls (p=0.018, r=+0.226). CONCLUSIONS: A later age was evidenced in CDs patients that reported licit/ilicit drug misuse. In CDs adolescent, substance use was more likely to have sexual intercourse. Our study reinforces that these patients should be systematically screened by pediatricians for drug related health behavioral patterns. PMID- 27354413 TI - Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage. AB - M-CSF and GM-CSF are 2 important cytokines that regulate macrophage numbers and function. Here, we review their known effects on cells of the macrophage-monocyte lineage. Important clues to their function come from their expression patterns. M CSF exhibits a mostly homeostatic expression pattern, whereas GM-CSF is a product of cells activated during inflammatory or pathologic conditions. Accordingly, M CSF regulates the numbers of various tissue macrophage and monocyte populations without altering their "activation" status. Conversely, GM-CSF induces activation of monocytes/macrophages and also mediates differentiation to other states that participate in immune responses [i.e., dendritic cells (DCs)]. Further insights into their function have come from analyses of mice deficient in either cytokine. M-CSF signals through its receptor (CSF-1R). Interestingly, mice deficient in CSF 1R expression exhibit a more significant phenotype than mice deficient in M-CSF. This observation was explained by the discovery of a novel cytokine (IL-34) that represents a second ligand of CSF-1R. Information about the function of these ligands/receptor system is still developing, but its complexity is intriguing and strongly suggests that more interesting biology remains to be elucidated. Based on our current knowledge, several therapeutic molecules targeting either the M CSF or the GM-CSF pathways have been developed and are currently being tested in clinical trials targeting either autoimmune diseases or cancer. It is intriguing to consider how evolution has directed these pathways to develop; their complexity likely mirrors the multiple functions in which cells of the monocyte/macrophage system are involved. PMID- 27354416 TI - Arabidopsis MAKR5 is a positive effector of BAM3-dependent CLE45 signaling. AB - Receptor kinases convey diverse environmental and developmental inputs by sensing extracellular ligands. In plants, one group of receptor-like kinases (RLKs) is characterized by extracellular leucine-rich repeat (LRR) domains, which interact with various ligands that include the plant hormone brassinosteroid and peptides of the CLAVATA3/EMBRYO SURROUNDING REGION (CLE) type. For instance, the CLE45 peptide requires the LRR-RLK BARELY ANY MERISTEM 3 (BAM3) to prevent protophloem formation in Arabidopsis root meristems. Here, we show that other proposed CLE45 receptors, the two redundantly acting LRR-RLKs STERILITY-REGULATING KINASE MEMBER 1 (SKM1) and SKM2 (which perceive CLE45 in the context of pollen tube elongation), cannot substitute for BAM3 in the root. Moreover, we identify MEMBRANE-ASSOCIATED KINASE REGULATOR 5 (MAKR5) as a post-transcriptionally regulated amplifier of the CLE45 signal that acts downstream of BAM3. MAKR5 belongs to a small protein family whose prototypical member, BRI1 KINASE INHIBITOR 1, is an essentially negative regulator of brassinosteroid signaling. By contrast, MAKR5 is a positive effector of CLE45 signaling, revealing an unexpected diversity in the conceptual roles of MAKR genes in different signaling pathways. PMID- 27354417 TI - The journal Impact Factor and alternative metrics: A variety of bibliometric measures has been developed to supplant the Impact Factor to better assess the impact of individual research papers. PMID- 27354418 TI - Siblings with severe pyruvate kinase deficiency and a complex genotype. AB - Siblings presented as neonates with severe jaundice and transfusion-dependent hemolytic anemia. Next-generation sequencing revealed both to have three heterozygous mutations in the gene encoding erythrocyte pyruvate kinase (PKLR), plus a heterozygous splice mutation in the beta-spectrin gene (SPTB). In addition, both have a different 5th mutation in a gene encoding other erythrocyte membrane proteins. The asymptomatic parents and all three asymptomatic siblings have different sets of these mutations. (c) 2016 Wiley Periodicals, Inc. PMID- 27354420 TI - Elucidation of Photoprotective Mechanisms of PSI Against Fluctuating Light photoinhibition. AB - It has been claimed that the cyclic electron flow around PSI (CEF-PSI) plays an important role in protection of PSI against fluctuating light photoinhibition. However, the photoprotective mechanism of PSI is not fully elucidated. Here, we examined the mechanism, using two CEF-PSI mutants of Arabidopsis thaliana, and antimycin A, an inhibitor of the PGR5 (proton gradient regulation 5)-mediated CEF PSI. Dark-adapted leaves in these plants were illuminated in fluctuating light alternating between high light at 1,200 umol m-2 s-1 and low light at 30 umol m-2 s-1 every 2 min, and PSI and PSII parameters were simultaneously measured for 160 min with 830 nm absorption and Chl fluorescence, respectively. When CEF-PSI, especially PGR5-mediated CEF-PSI, did not operate, the acceptor-side limitation of PSI, Y(NA), increased stepwise, leading to marked PSI photoinhibition. The deficiency of CFE-PSI decreased not only the electron transport rate through PSI but also the donor-side limitation of PSI, Y(ND), in high light phases. These results showed that the large Y(ND), observed only when CEF-PSI operated, contributed to suppression of PSI photoinhibition. Taken together with our previous report that high Y(NA) was alleviated by the enhancement of CEF-PSI, a model for the protective mechanisms of PSI is proposed. In this model, both alleviation of Y(NA) and acceleration of Y(ND) are indispensable, and for realization of such a situation, regulation of the electron flows, especially the PGR5-mediated CEF-PSI, plays a key role. It is important for effective protection to regulate the balance of Y(ND) and Y(NA) through CEF-PSI. PMID- 27354419 TI - Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice. AB - Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen treatment raises plasma TGs in women, but molecular mechanisms remain poorly understood. Here we explore the role of cholesteryl ester transfer protein (CETP) in the regulation of TG metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, increased TG production, and increased expression of genes involved in VLDL synthesis, but not in nontransgenic littermate females. In CETP females, estrogen enhanced expression of small heterodimer partner (SHP), a nuclear receptor regulating VLDL production. Deletion of liver SHP prevented increases in TG production and expression of genes involved in VLDL synthesis in CETP mice with estrogen treatment. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased liver beta-oxidation and reduced liver TG content by 60%. Liver estrogen receptor alpha (ERalpha) was required for CETP expression to enhance beta-oxidation and reduce liver TG content. Thus, CETP alters at least two networks governing TG metabolism, one involving SHP to increase VLDL-TG production in response to estrogen, and another involving ERalpha to enhance beta-oxidation and lower liver TG content. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism. PMID- 27354421 TI - Involvement of OST1 Protein Kinase and PYR/PYL/RCAR Receptors in Methyl Jasmonate Induced Stomatal Closure in Arabidopsis Guard Cells. AB - Methyl jasmonate (MeJA) induces stomatal closure. It has been shown that stomata of many ABA-insensitive mutants are also insensitive to MeJA, and a low amount of ABA is a prerequisite for the MeJA response. However, the molecular mechanisms of the interaction between ABA and MeJA signaling remain to be elucidated. Here we studied the interplay of signaling of the two hormones in guard cells using the quadruple ABA receptor mutant pyr1 pyl1 pyl2 pyl4 and ABA-activated protein kinase mutants ost1-2 and srk2e. In the quadruple mutant, MeJA-induced stomatal closure, H2O2 production, nitric oxide (NO) production, cytosolic alkalization and plasma membrane Ca(2+)-permeable current (ICa) activation were not impaired. At the same time, the inactivation of the inward-rectifying K(+) current was impaired. In contrast to the quadruple mutant, MeJA-induced stomatal closure, H2O2 production, NO production and cytosolic alkalization were impaired in ost1-2 and srk2e as well as in aba2-2, the ABA-deficient mutant. The activation of ICa was also impaired in srk2e. Collectively, these results indicated that OST1 was essential for MeJA-induced stomatal closure, while PYR1, PYL1, PYL2 and PYL4 ABA receptors were not sufficient factors. MeJA did not appear to activate OST1 kinase activity. This implies that OST1 mediates MeJA signaling through an undetectable level of activity or a non-enzymatic action. MeJA induced the expression of an ABA synthesis gene, NCED3, and increased ABA contents only modestly. Taken together with previous reports, this study suggests that MeJA signaling in guard cells is primed by ABA and is not brought about through the pathway mediated by PYR1, PYL1 PYL2 and PYL4. PMID- 27354422 TI - Systolic Blood Pressure Intervention Trial (SPRINT) and Target Systolic Blood Pressure in Future Hypertension Guidelines. AB - The Systolic Blood Pressure (SBP, mm Hg) Intervention Trial (SPRINT) showed that targeting SBP <120 mm Hg (intensive treatment, mean SBP: 121.5 mm Hg) versus <140 (standard treatment, mean SBP: 134.6 mm Hg) reduced cardiovascular events 25%. SPRINT has 2 implicit assumptions that could impact future US hypertension guidelines: (1) standard therapy controlled SBP similarly to that in adults with treated hypertension and (2) intensive therapy produced a lower mean SBP than in adults with treated hypertension and SBP <140 mm Hg. To examine these assumptions, US National Health and Nutrition Examination Survey 2009 to 2012 data were analyzed on 3 groups of adults with treated hypertension: group 1 consisted of SPRINT-like participants aged >=50 years; group 2 consisted of participants all aged >=18 years; and group 3 consisted of participants aged >=18 years excluding group 1 but otherwise similar to SPRINT-like participants except high cardiovascular risk. Mean SBPs in groups 1, 2, and 3 were 133.0, 130.1, and 124.6, with 66.2%, 72.2%, and 81.9%, respectively, controlled to SBP <140; 68.3%, 74.8%, and 83.4% of the controlled subset had SBP <130. Mean SBPs in those controlled to <140 were 123.3, 120.9, and 118.9, respectively. Among US adults with treated hypertension, (1) the SPRINT-like group had higher mean SBP than comparison groups, yet lower than SPRINT standard treatment group and (2) among groups 1 to 3 with SBP <140, SBP values were within <3 mm Hg of SPRINT intensive treatment. SPRINT results suggest that treatment should be continued and not reduced when treated SBP is <130, especially for the SPRINT-like subset. Furthermore, increasing the percentage of treated adults with SBP <140 could approximate SPRINT intensive treatment SBP without lowering treatment goals. PMID- 27354423 TI - Remote Zone Extracellular Volume and Left Ventricular Remodeling in Survivors of ST-Elevation Myocardial Infarction. AB - The natural history and pathophysiological significance of tissue remodeling in the myocardial remote zone after acute ST-elevation myocardial infarction (STEMI) is incompletely understood. Extracellular volume (ECV) in myocardial regions of interest can now be measured with cardiac magnetic resonance imaging. Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI [British Heart Foundation Magnetic Resonance Imaging in Acute ST-Segment Elevation Myocardial Infarction study]). Cardiac magnetic resonance was performed at 1.5 Tesla at 2 days and 6 months post STEMI. T1 modified Look-Locker inversion recovery mapping was performed before and 15 minutes after contrast (0.15 mmol/kg gadoterate meglumine) in 140 patients at 2 days post STEMI (mean age: 59 years, 76% male) and in 131 patients at 6 months post STEMI. Remote zone ECV was lower than infarct zone ECV (25.6+/-2.8% versus 51.4+/-8.9%; P<0.001). In multivariable regression, left ventricular ejection fraction was inversely associated with remote zone ECV (P<0.001), and diabetes mellitus was positively associated with remote zone ECV (P=0.010). No ST-segment resolution (P=0.034) and extent of ischemic area at risk (P<0.001) were multivariable associates of the change in remote zone ECV at 6 months (DeltaECV). DeltaECV was a multivariable associate of the change in left ventricular end-diastolic volume at 6 months (regression coefficient [95% confidence interval]: 1.43 (0.10-2.76); P=0.036). DeltaECV is implicated in the pathophysiology of left ventricular remodeling post STEMI, but because the effect size is small, DeltaECV has limited use as a clinical biomarker of remodeling. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02072850. PMID- 27354425 TI - Prehypertension During Normotensive Pregnancy and Postpartum Clustering of Cardiometabolic Risk Factors: A Prospective Cohort Study. AB - The nonstratification of blood pressure (BP) levels may underestimate future cardiovascular risk in pregnant women who present with BP levels in the range of prehypertension (120-139/80-89 mm Hg). We prospectively evaluated the relationship between multiple antepartum BP measurements (from 11(+0) to 13(+6) weeks' gestation to term) and the occurrence of postpartum metabolic syndrome in 507 normotensive pregnant women after a live birth. By using latent class growth modeling, we identified the following 3 distinctive diastolic BP (DBP) trajectory groups: the low-J-shaped group (34.2%; DBP from 62.5+/-5.8 to 65.0+/-6.8 mm Hg), the moderate-U-shaped group (52.6%; DBP from 71.0+/-5.9 to 69.8+/-6.2 mm Hg), and the elevated-J-shaped group (13.2%; DBP from 76.2+/-6.7 to 81.8+/-4.8 mm Hg). Notably, the elevated-J-shaped trajectory group had mean DBP and systolic BP levels within the range of prehypertension from 37(+0) and 26(+0) weeks of pregnancy, respectively. Among the 309 women who completed the ~1.6 years of postpartum follow-up, the women in the elevated-J-shaped group had greater odds of developing postpartum metabolic syndrome (adjusted odds ratio, 6.55; 95% confidence interval, 1.79-23.92; P=0.004) than the low-J-shaped group. Moreover, a parsimonious model incorporating DBP (membership in the elevated-J-shaped group but not in the DBP prehypertension group as identified by a single measurement) and elevated levels of fasting glucose (>4.99 mmol/L) and triglycerides (>3.14 mmol/L) at term was developed, with good discrimination and calibration for postpartum metabolic syndrome (c-statistic, 0.764; 95% confidence interval, 0.674 0.855; P<0.001). Therefore, prehypertension identified by DBP trajectories throughout pregnancy is an independent risk factor for predicting postpartum metabolic syndrome in normotensive pregnant women. PMID- 27354426 TI - Is It Time to Reappraise Blood Pressure Thresholds and Targets? A Statement From the International Society of Hypertension-A Global Perspective. PMID- 27354424 TI - Masked Hypertension and Cardiovascular Disease Events in a Prospective Cohort of Blacks: The Jackson Heart Study. AB - Masked hypertension, defined as nonelevated clinic blood pressure (BP) with elevated out-of-clinic BP, has been associated with increased cardiovascular disease (CVD) risk in Europeans and Asians. Few data are available on masked hypertension and CVD and mortality risk among blacks. We analyzed data from the Jackson Heart Study, a prospective cohort study of blacks. Analyses included participants with clinic-measured systolic/diastolic BP <140/90 mm Hg who completed ambulatory BP monitoring after the baseline examination in 2000 to 2004 (n=738). Masked daytime (10:00 am-8:00 pm) hypertension was defined as mean ambulatory systolic/diastolic BP >=135/85 mm Hg. Masked nighttime (midnight to 6:00 am) hypertension was defined as mean ambulatory systolic/diastolic BP >=120/70 mm Hg. Masked 24-hour hypertension was defined as mean systolic/diastolic BP >=130/80 mm Hg. CVD events (nonfatal/fatal stroke, nonfatal myocardial infarction, or fatal coronary heart disease) and deaths identified through December 2010 were adjudicated. Any masked hypertension (masked daytime, nighttime, or 24-hour hypertension) was present in 52.2% of participants; 28.2%, 48.2% and 31.7% had masked daytime, nighttime, and 24-hour hypertension, respectively. There were 51 CVD events and 44 deaths during a median follow-up of 8.2 and 8.5 years, respectively. CVD rates per 1000 person-years (95% confidence interval) in participants with and without any masked hypertension were 13.5 (9.9 18.4) and 3.9 (2.2-7.1), respectively. The multivariable adjusted hazard ratio (95% confidence interval) for CVD was 2.49 (1.26-4.93) for any masked hypertension and 2.86 (1.59-5.13), 2.35 (1.23-4.50), and 2.52 (1.39-4.58) for masked daytime, nighttime, and 24-hour hypertension, respectively. Masked hypertension was not associated with all-cause mortality. Masked hypertension is common and associated with increased risk for CVD events in blacks. PMID- 27354428 TI - Thickness dependence on the optoelectronic properties of multilayered GaSe based photodetector. AB - Two-dimensional (2D) layered materials exhibit unique optoelectronic properties at atomic thicknesses. In this paper, we fabricated metal-semiconductor-metal based photodetectors using layered gallium selenide (GaSe) with different thicknesses. The electrical and optoelectronic properties of the photodetectors were studied, and these devices showed good electrical characteristics down to GaSe flake thicknesses of 30 nm. A photograting effect was observed in the absence of a gate voltage, thereby implying a relatively high photoresponsivity. Higher values of the photoresponsivity occurred for thicker layers of GaSe with a maximum value 0.57 AW(-1) and external quantum efficiency of of 132.8%, and decreased with decreasing GaSe flake thickness. The detectivity was 4.05 * 10(10) cm Hz(1/2) W(-1) at 532 nm laser wavelength, underscoring that GaSe is a promising p-type 2D material for photodetection applications in the visible spectrum. PMID- 27354429 TI - The effects of an early motor skill intervention on motor skills, levels of physical activity, and socialization in young children with autism spectrum disorder: A pilot study. AB - Despite evidence suggesting one of the earliest indicators of an eventual autism spectrum disorder diagnoses is an early motor delay, there remain very few interventions targeting motor behavior as the primary outcome for young children with autism spectrum disorder. The aim of this pilot study was to measure the efficacy of an intensive motor skill intervention on motor skills (Test of Gross Motor Development-2), physical activity (accelerometers), and socialization (Playground Observation of Peer Engagement) in young children with autism spectrum disorder. A total of 20 children with autism spectrum disorder aged 4-6 years participated. The experimental group ( n = 11) participated in an 8-week intervention consisting of motor skill instruction for 4 h/day, 5 days/week. The control group ( n = 9) did not receive the intervention. A repeated-measures analysis of covariance revealed statistically significant differences between groups in all three motor outcomes, locomotor ( F(1, 14) = 10.07, p < 0.001, partial eta2 = 0.42), object control ( F(1, 14) = 12.90, p < 0.001, partial eta2 = 0.48), and gross quotient ( F(1, 14) = 15.61, p < 0.01, partial eta2 = 0.53). Findings shed light on the importance of including motor programming as part of the early intervention services delivered to young children with autism spectrum disorder. PMID- 27354427 TI - Interactions Between the Immune and the Renin-Angiotensin Systems in Hypertension. PMID- 27354430 TI - Psychological impacts of challenging behaviour and motivational orientation in staff supporting individuals with autistic spectrum conditions. AB - Despite increased risk of experiencing challenging behaviour, psychological impacts on community and residential staff supporting adults with autistic spectrum conditions are under-explored. Studies examining related roles indicate protective psychological factors may help maintain staff well-being. This study investigated relationships between motivational orientation (eudaimonic or hedonic), challenging behaviour frequency and type (physical, verbal or self injurious) and psychological impacts (anxiety, depression and life satisfaction). Participants (N = 99) were recruited from six organisations providing autism specific adult services within Scotland. A series of binary logistic regressions demonstrated weekly challenging behaviour exposure (compared to monthly or daily) significantly increased the likelihood of anxiety caseness. Increased eudaimonic motivation significantly reduced the likelihood of anxiety caseness while also predicting higher life satisfaction. Furthermore, having high levels of eudaimonic motivation appeared to moderate the impact of weekly challenging behaviour exposure on anxiety. No motivational orientation or challenging behaviour factor significantly predicted depression. This sample also demonstrated higher anxiety, lower depression and equivalent life satisfaction levels compared with general population norms. The results highlight the need for considering staff's motivational orientations, their frequency of exposure to challenging behaviour, and both positive and negative psychological outcomes, if seeking to accurately quantify or improve well-being in this staff population. PMID- 27354431 TI - Conducting research with minimally verbal participants with autism spectrum disorder. AB - A growing number of research groups are now including older minimally verbal individuals with autism spectrum disorder in their studies to encompass the full range of heterogeneity in the population. There are numerous barriers that prevent researchers from collecting high-quality data from these individuals, in part because of the challenging behaviors with which they present alongside their very limited means for communication. In this article, we summarize the practices that we have developed, based on applied behavioral analysis techniques, and have used in our ongoing research on behavioral, eye-tracking, and electrophysiological studies of minimally verbal children and adolescents with autism spectrum disorder. Our goal is to provide the field with useful guidelines that will promote the inclusion of the entire spectrum of individuals with autism spectrum disorder in future research investigations. PMID- 27354432 TI - The developmental trajectory of parent-report and objective sleep profiles in autism spectrum disorder: Associations with anxiety and bedtime routines. AB - The present study compared the course of parent-report and actigraphy-derived sleep profiles over a 1-year period, in school-age children with autism spectrum disorder and typically developing children. The Children's Sleep Habits Questionnaire and 14 nights of actigraphy were used to assess sleep profiles. Parents also completed the Spence Children's Anxiety Scale, the Social Worries Questionnaire and the Bedtime Routines Questionnaire. Between-group differences in parent-reported sleep problems were less pronounced at follow-up compared to baseline. The course of objective sleep was comparable between groups, with a significant reduction in sleep duration over time in both groups. Children with autism spectrum disorder were further characterised by significantly more night to-night variability in sleep quality, across both time points. Reductions over time in parent-reported sleep problems were significantly associated with reduced anxiety. Reductions in actigraphy-derived sleep efficiency were associated with an increased frequency of maladaptive activities in the hour before bedtime, in both children with and without autism spectrum disorder. PMID- 27354433 TI - Effects of various hydrogenated treatments on formation and photocatalytic activity of black TiO2 nanowire arrays. AB - The effects of hydrogen thermal and plasma treatment on the formation and photocatalytic activities of black TiO2 nanowire arrays were investigated and discussed. After either the hydrogen thermal or plasma treatment, the TiO2 nanowires remained. However, in contrast to the plasma treated nanowires, the diameter of the thermal treated TiO2 nanowires reduced more significantly, which was attributed to a thicker surface amorphous layer and more oxygen vacancies. A higher photoresponse in both UV and visible light regions and more hydroxide groups were also observed for the thermal treated nanowires. In addition, the black nanowires possessed greater carrier concentration, leading to a more efficient separation of electron-hole pairs. As a consequence, much enhanced photoelectrochemical water splitting and photocatalytic degradation of methylene blue were obtained. PMID- 27354434 TI - Highly flexible binder-free core-shell nanofibrous electrode for lightweight electrochemical energy storage using recycled water bottles. AB - The creation of a novel flexible nanocomposite fiber with conductive polymer polyaniline (PAni) coating on a polyethylene terephthalate (PET) substrate allowed for increased electrochemical performance while retaining ideal mechanical properties such as very high flexibility. Binder-free PAni-wrapped PET (PAni@PET) fiber with a core-shell structure was successfully fabricated through a novel technique. The PET nanofiber substrate was fabricated through an optimized electrospinning method, while the PAni shell was chemically polymerized onto the surface of the nanofibers. The PET substrate can be made directly from recycled PETE1 grade plastic water bottles. The resulting nanofiber with an average diameter of 121 nm +/- 39 nm, with a specific surface area of 83.72 m(2) g(-1), led to better ionic interactions at the electrode/electrolyte interface. The PAni active layer coating was found to be 69 nm in average thickness. The specific capacitance was found to have increased dramatically from pure PAni with carbon binders. The specific capacitance was found to be 347 F g(-1) at a relatively high scan rate of 10 mV s(-1). The PAni/PET fiber also experienced very little degradation (4.4%) in capacitance after 1500 galvanostatic charge/discharge cycles at a specific current of 1.2 A g(-1). The mesoporous structure of the PAni@PET fibrous mat also allowed for tunable capacitance by controlling the pore sizes. This novel fabrication method offers insights for the utilization of recycled PETE1 based bottles as a high performance, low cost, highly flexible supercapacitor device. PMID- 27354435 TI - Medical involvement in torture today? PMID- 27354436 TI - The Importance of Interspecific Interactions on the Present Range of the Invasive Mosquito Aedes albopictus (Diptera: Culicidae) and Persistence of Resident Container Species in the United States. AB - Aedes albopictus (Skuse) established in the United States over 30 yr ago and quickly spread throughout the entire eastern half of the country. It has recently spread into western regions and projected climate change scenarios suggest continued expansion to the west and north. Aedes albopictus has had major impacts on, and been impacted by, a diverse array of resident mosquito species. Laying eggs at the edges of small, water-holding containers, hatched larvae develop within these containers feeding on detritus-based resources. Under limited resource conditions, Ae. albopictus has been shown to be a superior competitor to essentially all native and resident species in the United States. Adult males also mate interspecifically with at least one resident species with significant negative impacts on reproductive output for susceptible females. Despite these strong interference effects on sympatric species, competitor outcomes have been highly variable, ranging from outright local exclusion by Ae. albopictus, to apparent exclusion of Ae. albopictus in the presence of the same species. Context dependent mechanisms that alter the relative strengths of inter- and intraspecific competition, as well as rapid evolution of satyrization-resistant females, may help explain these patterns of variable coexistence. Although there is a large body of research on interspecific interactions of Ae. albopictus in the United States, there remain substantial gaps in our understanding of the most important species interactions. Addressing these gaps is important in predicting the future distribution of this species and understanding consequences for resident species, including humans, that interact with this highly invasive mosquito. PMID- 27354437 TI - What Can Larval Ecology Tell Us About the Success of Aedes albopictus (Diptera: Culicidae) Within the United States? AB - Aedes albopictus (Skuse) was introduced in the United States approximately 30 years ago, and since has become an important pest and vector of disease. This species uses small water-holding containers as sites for oviposition and larval development. Larvae can consume a wide range of detritus-based energy sources, including microorganisms, and as such the type and quantity of detritus that enters these systems have been studied for the effects on adult populations. This review examines the documented responses of Ae. albopictus to different larval environments within the United States, and some of its unique ecology that may lead to a better understanding of its spread and success. Field surveys generally find larvae in shaded containers with high amounts of organic detritus. Larvae have higher survival and population growth under high amounts of detritus and microorganisms, but they also can outcompete other species when nutrients are limiting. Allocation of time to feeding by larvae is greater and more focused compared with resident species. These latter two points also may explain differences in carbon and nitrogen composition (nutrient stoichiometry), which point to a lower need for nitrogen. Combined, these facts suggest that the Ae. albopictus is a species with a relatively wide niche that had been able to exploit container habitats in the United States better than resident species. After 30 yr of research, only a narrow range of detritus types and environmental conditions have been examined. Data on factors affecting the production of adults and its spread and apparent success are still needed. PMID- 27354439 TI - Thirty Years of Aedes albopictus (Diptera: Culicidae) in America: An Introduction to Current Perspectives and Future Challenges. PMID- 27354438 TI - Photoperiodic Diapause and the Establishment of Aedes albopictus (Diptera: Culicidae) in North America. AB - The invasion and range expansion of Aedes albopictus (Skuse) in North America represents an outstanding opportunity to study processes of invasion, range expansion, and climatic adaptation. Furthermore, knowledge obtained from such research is relevant to developing novel strategies to control this important vector species. Substantial evidence indicates that the photoperiodic diapause response is an important adaptation to climatic variation across the range of Ae. albopictus in North America. Photoperiodic diapause is a key determinant of abundance in both space and time, and the timing of entry into and exit out of diapause strongly affects seasonal population dynamics and thus the potential for arbovirus transmission. Emerging genomic technologies are making it possible to develop high-resolution, genome-wide genetic markers that can be used for genetic mapping of traits relevant to disease transmission and phylogeographic studies to elucidate invasion history. Recent work using next-generation sequencing technologies (e.g., RNA-seq), combined with physiological experiments, has provided extensive insight into the transcriptional basis of the diapause response in Ae. albopictus Applying this knowledge to identify novel targets for vector control represents an important future challenge. Finally, recent studies have begun to identify traits other than diapause that are affected by photoperiodism. Extending this work to identify additional traits influenced by photoperiod should produce important insights into the seasonal biology of Ae. albopictus. PMID- 27354440 TI - The Eye of the Tiger, the Thrill of the Fight: Effective Larval and Adult Control Measures Against the Asian Tiger Mosquito, Aedes albopictus (Diptera: Culicidae), in North America. AB - The Asian tiger mosquito, Aedes albopictus (Skuse), is a highly invasive container-inhabiting species with a global distribution. This mosquito, similar to other Stegomyia species such as Aedes aegypti (L.), is highly adapted to urban and suburban areas, and commonly oviposits in artificial containers, which are ubiquitous in these peridomestic environments. The increase in speed and amount of international travel and commerce, coupled with global climate change, have aided in the resurgence and expansion of Stegomyia species into new areas of North America. In many parts of their range, both species are implicated as significant vectors of emerging and re-emerging arboviruses such as dengue, chikungunya, and now Zika. Although rapid and major advances have been made in the field of biology, ecology, genetics, taxonomy, and virology, relatively little has changed in the field of mosquito control in recent decades. This is particularly discouraging in regards to container-inhabiting mosquitoes, because traditional integrated mosquito management (IMM) approaches have not been effective against these species. Many mosquito control programs simply do not possess the man-power or necessary financial resources needed to suppress Ae. albopictus effectively. Therefore, control of mosquito larvae, which is the foundation of IMM approaches, is exceptionally difficult over large areas. This review paper addresses larval habitats, use of geographic information systems for habitat preference detection, door-to-door control efforts, source reduction, direct application of larvicides, biological control agents, area-wide low-volume application of larvicides, hot spot treatments, autodissemination stations, public education, adult traps, attractive-toxic sugar bait methods, lethal ovitraps, barrier-residual adulticides, hand-held ultra-low-volume adulticides, area-wide adulticides applied by ground or air, and genetic control methods. The review concludes with future recommendations for practitioners, researchers, private industry, and policy makers. PMID- 27354441 TI - Viral-templated gold/polypyrrole nanopeapods for an ammonia gas sensor. AB - One-dimensional gold/polypyrrole (Au/PPy) nanopeapods were fabricated using a viral template: M13 bacteriophage. The genetically modified filamentous virus displayed gold-binding peptides along its length, allowing selective attachment of gold nanoparticles (Au NPs) under ambient conditions. A PPy shell was electropolymerized on the viral-templated Au NP chains forming nanopeapod structures. The PPy shell morphology and thickness were controlled through electrodeposition potential and time, resulting in an ultra-thin conductive polymer shell of 17.4 +/- 3.3 nm. A post-electrodeposition acid treatment was used to modify the electrical properties of these hybrid materials. The electrical resistance of the nanopeapods was monitored at each assembly step. Chemiresistive ammonia (NH3) gas sensors were developed from networks of the hybrid Au/PPy nanostructures. Room temperature sensing performance was evaluated from 5 to 50 ppmv and a mixture of reversible and irreversible chemiresistive behavior was observed. A sensitivity of 0.30%/ppmv was found for NH3 concentrations of 10 ppmv or less, and a lowest detection limit (LDL) of 0.007 ppmv was calculated. Furthermore, acid-treated devices exhibited an enhanced sensitivity of 1.26%/ppmv within the same concentration range and a calculated LDL of 0.005 ppmv. PMID- 27354442 TI - Porphyromonas gulae Has Virulence and Immunological Characteristics Similar to Those of the Human Periodontal Pathogen Porphyromonas gingivalis. AB - Periodontitis is a significant problem in companion animals, and yet little is known about the disease-associated microbiota. A major virulence factor for the human periodontal pathogen Porphyromonas gingivalis is the lysyl- and arginyl specific proteolytic activity of the gingipains. We screened several Porphyromonas species isolated from companion animals-P. asaccharolytica, P. circumdentaria, P. endodontalis, P. levii, P. gulae, P. macacae, P. catoniae, and P. salivosa-for Lys- and Arg-specific proteolytic activity and compared the epithelial and macrophage responses and induction of alveolar bone resorption of the protease active species to that of Porphyromonas gingivalis Only P. gulae exhibited Lys-and Arg-specific proteolytic activity. The genes encoding the gingipains (RgpA/B and Kgp) were identified in the P. gulae strain ATCC 51700 and all publicly available 12 draft genomes of P. gulae strains. P. gulae ATCC 51700 induced levels of alveolar bone resorption in an animal model of periodontitis similar to those in P. gingivalis W50 and exhibited a higher capacity for autoaggregation and binding to oral epithelial cells with induction of apoptosis. Macrophages (RAW 264.7) were found to phagocytose P. gulae ATCC 51700 and the fimbriated P. gingivalis ATCC 33277 at similar levels. In response to P. gulae ATCC 51700, macrophages secreted higher levels of cytokines than those induced by P. gingivalis ATCC 33277 but lower than those induced by P. gingivalis W50, except for the interleukin-6 response. Our results indicate that P. gulae exhibits virulence characteristics similar to those of the human periodontal pathogen P. gingivalis and therefore may play a key role in the development of periodontitis in companion animals. PMID- 27354443 TI - Identification of Signaling Pathways by Which CD40 Stimulates Autophagy and Antimicrobial Activity against Toxoplasma gondii in Macrophages. AB - CD40 is an important stimulator of autophagy and autophagic killing of Toxoplasma gondii in host cells. In contrast to autophagy induced by nutrient deprivation or pattern recognition receptors, less is known about the effects of cell-mediated immunity on Beclin 1 and ULK1, key regulators of autophagy. Here we studied the molecular mechanisms by which CD40 stimulates autophagy in macrophages. CD40 ligation caused biphasic Jun N-terminal protein kinase (JNK) phosphorylation. The second phase of JNK phosphorylation was dependent on autocrine production of tumor necrosis factor alpha (TNF-alpha). TNF-alpha and JNK signaling were required for the CD40-induced increase in autophagy. JNK signaling downstream of CD40 caused Ser-87 phosphorylation of Bcl-2 and dissociation between Bcl-2 and Beclin 1, an event known to stimulate the autophagic function of Beclin 1. However, TNF-alpha alone was unable to stimulate autophagy. CD40 also stimulated autophagy via a pathway that included calcium/calmodulin-dependent kinase kinase beta (CaMKKbeta), AMP-activated protein kinase (AMPK), and ULK1. CD40 caused AMPK phosphorylation at its activating site, Thr-172. This effect was mediated by CaMKKbeta and was not impaired by neutralization of TNF-alpha. CD40 triggered AMPK-dependent Ser-555 phosphorylation of ULK1. CaMKKbeta, AMPK, and ULK1 were required for CD40-induced increase in autophagy. CD40-mediated autophagic killing of Toxoplasma gondii is known to require TNF-alpha. Knockdown of JNK, CaMKKbeta, AMPK, or ULK1 prevented T. gondii killing in CD40-activated macrophages. The second phase of JNK phosphorylation-Bcl-2 phosphorylation-Bcl-2-Beclin 1 dissociation and AMPK phosphorylation-ULK1 phosphorylation occurred simultaneously at ~4 h post-CD40 stimulation. Thus, CaMKKbeta and TNF-alpha are upstream molecules by which CD40 acts on ULK1 and Beclin 1 to stimulate autophagy and killing of T. gondii. PMID- 27354444 TI - Impact of sarA and Phenol-Soluble Modulins on the Pathogenesis of Osteomyelitis in Diverse Clinical Isolates of Staphylococcus aureus. AB - We used a murine model of acute, posttraumatic osteomyelitis to evaluate the virulence of two divergent Staphylococcus aureus clinical isolates (the USA300 strain LAC and the USA200 strain UAMS-1) and their isogenic sarA mutants. The results confirmed that both strains caused comparable degrees of osteolysis and reactive new bone formation in the acute phase of osteomyelitis. Conditioned medium (CM) from stationary-phase cultures of both strains was cytotoxic to cells of established cell lines (MC3TC-E1 and RAW 264.7 cells), primary murine calvarial osteoblasts, and bone marrow-derived osteoclasts. Both the cytotoxicity of CM and the reactive changes in bone were significantly reduced in the isogenic sarA mutants. These results confirm that sarA is required for the production and/or accumulation of extracellular virulence factors that limit osteoblast and osteoclast viability and that thereby promote bone destruction and reactive bone formation during the acute phase of S. aureus osteomyelitis. Proteomic analysis confirmed the reduced accumulation of multiple extracellular proteins in the LAC and UAMS-1 sarA mutants. Included among these were the alpha class of phenol soluble modulins (PSMs), which were previously implicated as important determinants of osteoblast cytotoxicity and bone destruction and repair processes in osteomyelitis. Mutation of the corresponding operon reduced the cytotoxicity of CM from both UAMS-1 and LAC cultures for osteoblasts and osteoclasts. It also significantly reduced both reactive bone formation and cortical bone destruction by CM from LAC cultures. However, this was not true for CM from cultures of a UAMS-1 psmalpha mutant, thereby suggesting the involvement of additional virulence factors in such strains that remain to be identified. PMID- 27354445 TI - Free Sialic Acid Acts as a Signal That Promotes Streptococcus pneumoniae Invasion of Nasal Tissue and Nonhematogenous Invasion of the Central Nervous System. AB - Streptococcus pneumoniae (pneumococcus) is a leading cause of bacterial meningitis and neurological sequelae in children worldwide. Acute bacterial meningitis is widely considered to result from bacteremia that leads to blood brain barrier breakdown and bacterial dissemination throughout the central nervous system (CNS). Previously, we showed that pneumococci can gain access to the CNS through a nonhematogenous route without peripheral blood infection. This access is thought to occur when the pneumococci in the upper sinus follow the olfactory nerves and enter the CNS through the olfactory bulbs. In this study, we determined whether the addition of exogenous sialic acid postcolonization promotes nonhematogenous invasion of the CNS. Previously, others showed that treatment with exogenous sialic acid post-pneumococcal infection increased the numbers of CFU recovered from an intranasal mouse model of infection. Using a pneumococcal colonization model, an in vivo imaging system, and a multiplex assay for cytokine expression, we demonstrated that sialic acid can increase the number of pneumococci recovered from the olfactory bulbs and brains of infected animals. We also show that pneumococci primarily localize to the olfactory bulb, leading to increased expression levels of proinflammatory cytokines and chemokines. These findings provide evidence that sialic acid can enhance the ability of pneumococci to disseminate into the CNS and provide details about the environment needed to establish nonhematogenous pneumococcal meningitis. PMID- 27354446 TI - Genomic Changes Associated with the Loss of Nocardia brasiliensis Virulence in Mice after 200 In Vitro Passages. AB - Nocardia species, particularly Nocardia brasiliensis, are etiologic agents of mycetoma, a chronic subcutaneous infection. Until now, little has been known about the pathogenic mechanisms involved in nocardial infection. Traditionally, subculture in rich media has been a simple way to induce attenuation. In this work, we report the changes in virulence toward mice and in genomic constitution of N. brasiliensis produced after 200 continuous subcultures in brain heart infusion (BHI) medium (P-200 strain). The ability of the N. brasiliensis P-200 strain to produce experimental infection was tested using BALB/c mice. P-200 was also used to immunize mice to determine whether it could induce resistance against a challenge with a nonsubcultured isolate (P-0). Comparative proteomic analysis between N. brasiliensis P-0 and P-200 was performed by two-dimensional (2-D) electrophoresis, and the genome sequence was obtained through Roche 454 sequence analysis. Virulence in BALB/c mice was completely lost, and BALB/c mice immunized with P-200 bacterial cells were resistant to mycetoma production by the nonsubcultured strain. Whole-genome sequence analysis revealed that P-200 lost a total of 262,913 bp distributed in 19 deleted regions, involving a total of 213 open reading frames (ORFs). The deleted genes included those encoding bacterial virulence factors, e.g., catalase, nitrate reductase enzymes, and a group of mammalian cell entry (MCE) family proteins, which may explain the loss of virulence of the isolate. Thus, completely attenuated N. brasiliensis was obtained after 200 passages in BHI medium, and putative Nocardia virulence genes were identified for the first time. PMID- 27354448 TI - Specifying the ovarian cancer risk threshold of 'premenopausal risk-reducing salpingo-oophorectomy' for ovarian cancer prevention: a cost-effectiveness analysis. AB - BACKGROUND: Risk-reducing salpingo-oophorectomy (RRSO) is the most effective intervention to prevent ovarian cancer (OC). It is only available to high-risk women with >10% lifetime OC risk. This threshold has not been formally tested for cost-effectiveness. OBJECTIVE: To specify the OC risk thresholds for RRSO being cost-effective for preventing OC in premenopausal women. METHODS: The costs as well as effects of surgical prevention ('RRSO') were compared over a lifetime with 'no RRSO' using a decision analysis model. RRSO was undertaken in premenopausal women >40 years. The model was evaluated at lifetime OC risk levels: 2%, 4%, 5%, 6%, 8% and 10%. Costs and outcomes are discounted at 3.5%. Uncertainty in the model was assessed using both deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA). Outcomes included in the analyses were OC, breast cancer (BC) and additional deaths from coronary heart disease. Total costs and effects were estimated in terms of quality-adjusted life years (QALYs); incidence of OC and BC; as well as incremental cost-effectiveness ratio (ICER). DATA SOURCES: Published literature, Nurses Health Study, British National Formulary, Cancer Research UK, National Institute for Health and Care Excellence guidelines and National Health Service reference costs. The time horizon is lifetime and perspective: payer. RESULTS: Premenopausal RRSO is cost effective at 4% OC risk (life expectancy gained=42.7 days, ICER=L19 536/QALY) with benefits largely driven by reduction in BC risk. RRSO remains cost-effective at >8.2% OC risk without hormone replacement therapy (ICER=L29 071/QALY, life expectancy gained=21.8 days) or 6%if BC risk reduction=0 (ICER=L27 212/QALY, life expectancy gained=35.3 days). Sensitivity analysis indicated results are not impacted much by costs of surgical prevention or treatment of OC/ BC or cardiovascular disease. However, results were sensitive to RRSO utility scores. Additionally, 37%, 61%, 74%, 84%, 96% and 99.5% simulations on PSA are cost effective for RRSO at the 2%, 4%, 5%, 6%, 8% and 10% levels of OC risk, respectively. CONCLUSIONS: Premenopausal RRSO appears to be extremely cost effective at >=4% lifetime OC risk, with >=42.7 days gain in life expectancy if compliance with hormone replacement therapy is high. Current guidelines should be re-evaluated to reduce the RRSO OC risk threshold to benefit a number of at-risk women who presently cannot access risk-reducing surgery. PMID- 27354447 TI - Long-Term Immunity to Trypanosoma cruzi in the Absence of Immunodominant trans Sialidase-Specific CD8+ T Cells. AB - Trypanosoma cruzi infection drives the expansion of remarkably focused CD8(+) T cell responses targeting epitopes encoded by variant trans-sialidase (TS) genes. Infection of C57BL/6 mice with T. cruzi results in up to 40% of all CD8(+) T cells committed to recognition of the dominant TSKB20 and subdominant TSKB18 TS epitopes. However, despite this enormous response, these mice fail to clear T. cruzi infection and subsequently develop chronic disease. One possible reason for the failure to cure T. cruzi infection is that immunodomination by these TS specific T cells may interfere with alternative CD8(+) T cell responses more capable of complete parasite elimination. To address this possibility, we created transgenic mice that are centrally tolerant to these immunodominant epitopes. Mice expressing TSKB20, TSKB18, or both epitopes controlled T. cruzi infection and developed effector CD8(+) T cells that maintained an activated phenotype. Memory CD8(+) T cells from drug-cured TSKB-transgenic mice rapidly responded to secondary T. cruzi infection. In the absence of the response to TSKB20 and TSKB18, immunodominance did not shift to other known subdominant epitopes despite the capacity of these mice to expand epitope-specific T cells specific for the model antigen ovalbumin expressed by engineered parasites. Thus, CD8(+) T cell responses tightly and robustly focused on a few epitopes within variant TS antigens appear to neither contribute to, nor detract from, the ability to control T. cruzi infection. These data also indicate that the relative position of an epitope within a CD8(+) immunodominance hierarchy does not predict its importance in pathogen control. PMID- 27354449 TI - Jellinek Memorial Award 2016 Winner Announced. PMID- 27354450 TI - Music Therapy and Spiritual Care in End-of-Life: A Qualitative Inquiry into Ethics and Training Issues Identified by Chaplains and Music Therapists. AB - BACKGROUND: Music therapists are increasingly employed by hospices. As such, they are often called upon to provide additional spiritual care to patients receiving end-of-life care. However, researchers have not yet examined the appropriateness of music therapists providing spiritual care as part of the hospice team, or ethics and training issues related to music therapist-led spiritual care. OBJECTIVE: The purpose of this study was to explore the thoughts and attitudes of hospice chaplains and music therapists (MTs) about ethics and training issues related to music therapists providing spiritual care as part of the hospice interdisciplinary team. METHODS: The study used semi-structured interviews with a purposive sample of music therapists and chaplains specializing in hospice care as part of a larger exploratory mixed methods study. Each interview was recorded, transcribed, and analyzed using a two-step process including both a modified phenomenological inductive approach and thematic analysis. RESULTS: Participants discussed ethics and training issues related to the provision of music therapist led spiritual care as part of the hospice team. These issues included scope of practice, cultural competence and maintaining personal boundaries, and spiritual care training topics such as educational content and educational methods. CONCLUSIONS: While it was clear that both chaplains and music therapists felt it was appropriate for music therapists to provide spiritual care as part of the hospice team, there is a need for formal and informal spiritual care training for music therapists doing this type of work. Training should potentially include information about comparative religions, cultural competence, scope of practice, and maintaining personal boundaries. PMID- 27354451 TI - Self-assembled growth of GaN nanowires on amorphous Al x O y : from nucleation to the formation of dense nanowire ensembles. AB - We present a comprehensive description of the self-assembled nucleation and growth of GaN nanowires (NWs) by plasma-assisted molecular beam epitaxy on amorphous Al x O y buffers (a-Al x O y ) prepared by atomic layer deposition. The results are compared with those obtained on nitridated Si(111). Using line-of sight quadrupole mass spectrometry, we analyze in situ the incorporation of Ga starting from the incubation and nucleation stages till the formation of the final nanowire ensemble and observe qualitatively the same time dependence for the two types of substrates. However, on a-Al x O y the incubation time is shorter and the nucleation faster than on nitridated Si. Moreover, on a-Al x O y we observe a novel effect of decrease in incorporated Ga flux for long growth durations which we explain by coalescence of NWs leading to reduction of the GaN surface area where Ga may reside. Dedicated samples are used to analyze the evolution of surface morphology. In particular, no GaN nuclei are detected when growth is interrupted during the incubation stage. Moreover, for a-Al x O y , the same shape transition from spherical cap-shaped GaN crystallites to the NW-like geometry is found as it is known for nitridated Si. However, while the critical radius for this transition is only slightly larger for a-Al x O y than for nitridated Si, the critical height is more than six times larger for a-Al x O y . Finally, we observe that in fully developed NW ensembles, the substrate no longer influences growth kinetics and the same N-limited axial growth rate is measured on both substrates. We conclude that the same nucleation and growth processes take place on a-Al x O y as on nitridated Si and that these processes are of a general nature. Quantitatively, nucleation proceeds somewhat differently, which indicates the influence of the substrate, but once shadowing limits growth processes to the upper part of the NW ensemble, they are not affected anymore by the type of substrate. PMID- 27354452 TI - Evaluating Continuity During Transfer to Adult Care: A Systematic Review. AB - CONTEXT: Appropriate outcomes are required to evaluate transition programs' ability to maintain care continuity during the transfer to adult care of youths with a chronic condition. OBJECTIVE: To identify the outcomes used to measure care continuity during transfer, and to analyze current evidence regarding the efficacy of transition programs. DATA SOURCES: PubMed (1948-2014), Web of Science (1945-2014), Embase (1947-2014), and the reference lists of the studies identified. STUDY SELECTION: Screening on titles and abstracts; full-text assessment by 2 reviewers independently. DATA EXTRACTION: By 2 reviewers independently, by using a Cochrane form adapted to observational studies, including bias assessment. RESULTS: Among the 23 studies retrieved, all but 5 were monocentric, 16 were cohorts (15 retrospective), 6 cross-sectional studies, and 1 randomized trial. The principal disease studied was diabetes (n = 11). We identified 24 indicators relating to 2 main aspects of continuity of care: engagement and retention in adult care. As designed, most studies probably overestimated engagement. A lack of adjustment for confounding factors was the main limitation of the few studies evaluating the efficacy of transition programs. LIMITATIONS: The assessment of bias was challenging, due to the heterogeneity and observational nature of the studies. CONCLUSIONS: This review highlights the paucity of knowledge about the efficacy of transition programs for ensuring care continuity during the transfer from pediatric to adult care. The outcomes identified are relevant and not specific to a disease. However, the prospective follow-up of patients initially recruited in pediatric care should be encouraged to limit an overestimation of care continuity. PMID- 27354453 TI - Extended- Versus Narrower-Spectrum Antibiotics for Appendicitis. AB - BACKGROUND AND OBJECTIVES: Appendicitis guidelines recommend either narrower- or extended-spectrum antibiotics for treatment of complicated appendicitis. The goal of this study was to compare the effectiveness of extended-spectrum versus narrower-spectrum antibiotics for children with appendicitis. METHODS: We performed a retrospective cohort study of children aged 3 to 18 years discharged between 2011 and 2013 from 23 freestanding children's hospitals with an appendicitis diagnosis and appendectomy performed. Subjects were classified as having complicated appendicitis if they had a postoperative length of stay >=3 days, a central venous catheter placed, major or severe illness classification, or ICU admission. The exposure of interest was receipt of systemic extended spectrum antibiotics (piperacillin +/- tazobactam, ticarcillin +/- clavulanate, ceftazidime, cefepime, or a carbapenem) on the day of appendectomy or the day after. The primary outcome was 30-day readmission for wound infection or repeat abdominal surgery. Multivariable logistic regression, propensity score weighting, and subgroup analyses were used to control for confounding by indication. RESULTS: Of 24 984 patients, 17 654 (70.7%) had uncomplicated appendicitis and 7330 (29.3%) had complicated appendicitis. Overall, 664 (2.7%) patients experienced the primary outcome, 1.1% among uncomplicated cases and 6.4% among complicated cases (P < .001). Extended-spectrum antibiotic exposure was significantly associated with the primary outcome in complicated (adjusted odds ratio, 1.43 [95% confidence interval, 1.06 to 1.93]), but not uncomplicated, (adjusted odds ratio, 1.32 [95% confidence interval, 0.88 to 1.98]) appendicitis. These odds ratios remained consistent across additional analyses. CONCLUSIONS: Extended-spectrum antibiotics seem to offer no advantage over narrower-spectrum agents for children with surgically managed acute uncomplicated or complicated appendicitis. PMID- 27354454 TI - Guidelines for Monitoring and Management of Pediatric Patients Before, During, and After Sedation for Diagnostic and Therapeutic Procedures: Update 2016. AB - The safe sedation of children for procedures requires a systematic approach that includes the following: no administration of sedating medication without the safety net of medical/dental supervision, careful presedation evaluation for underlying medical or surgical conditions that would place the child at increased risk from sedating medications, appropriate fasting for elective procedures and a balance between the depth of sedation and risk for those who are unable to fast because of the urgent nature of the procedure, a focused airway examination for large (kissing) tonsils or anatomic airway abnormalities that might increase the potential for airway obstruction, a clear understanding of the medication's pharmacokinetic and pharmacodynamic effects and drug interactions, appropriate training and skills in airway management to allow rescue of the patient, age- and size-appropriate equipment for airway management and venous access, appropriate medications and reversal agents, sufficient numbers of staff to both carry out the procedure and monitor the patient, appropriate physiologic monitoring during and after the procedure, a properly equipped and staffed recovery area, recovery to the presedation level of consciousness before discharge from medical/dental supervision, and appropriate discharge instructions. This report was developed through a collaborative effort of the American Academy of Pediatrics and the American Academy of Pediatric Dentistry to offer pediatric providers updated information and guidance in delivering safe sedation to children. PMID- 27354455 TI - Do Bacteria in the Gut Set the Stage for Who Gets Viral Bronchiolitis and Its Severity? PMID- 27354456 TI - The Fecal Microbiota Profile and Bronchiolitis in Infants. AB - BACKGROUND: Little is known about the association of gut microbiota, a potentially modifiable factor, with bronchiolitis in infants. We aimed to determine the association of fecal microbiota with bronchiolitis in infants. METHODS: We conducted a case-control study. As a part of multicenter prospective study, we collected stool samples from 40 infants hospitalized with bronchiolitis. We concurrently enrolled 115 age-matched healthy controls. By applying 16S rRNA gene sequencing and an unbiased clustering approach to these 155 fecal samples, we identified microbiota profiles and determined the association of microbiota profiles with likelihood of bronchiolitis. RESULTS: Overall, the median age was 3 months, 55% were male, and 54% were non-Hispanic white. Unbiased clustering of fecal microbiota identified 4 distinct profiles: Escherichia-dominant profile (30%), Bifidobacterium-dominant profile (21%), Enterobacter/Veillonella-dominant profile (22%), and Bacteroides-dominant profile (28%). The proportion of bronchiolitis was lowest in infants with the Enterobacter/Veillonella-dominant profile (15%) and highest in the Bacteroides dominant profile (44%), corresponding to an odds ratio of 4.59 (95% confidence interval, 1.58-15.5; P = .008). In the multivariable model, the significant association between the Bacteroides-dominant profile and a greater likelihood of bronchiolitis persisted (odds ratio for comparison with the Enterobacter/Veillonella-dominant profile, 4.24; 95% confidence interval, 1.56 12.0; P = .005). In contrast, the likelihood of bronchiolitis in infants with the Escherichia-dominant or Bifidobacterium-dominant profile was not significantly different compared with those with the Enterobacter/Veillonella-dominant profile. CONCLUSIONS: In this case-control study, we identified 4 distinct fecal microbiota profiles in infants. The Bacteroides-dominant profile was associated with a higher likelihood of bronchiolitis. PMID- 27354457 TI - Gross Motor Milestones and Subsequent Development. AB - OBJECTIVE: We examined the longitudinal associations of age at achieving gross motor milestones and children's development in a US cohort of singletons and twins. METHODS: In the Upstate KIDS study, a population-based study of children born between 2008 and 2010, information on age at achievement of motor milestones and developmental skills was available in 599 children (314 singletons, 259 twins, and 26 triplets). Mothers reported their children's major motor milestones at ~4, 8, 12, 18, and 24 months. At age 4 years, children's development was clinically assessed by using the Battelle Developmental Inventory, Second Edition (BDI-2). Primary analyses by using multivariate linear regressions were conducted in singletons. We also examined the associations in twins. RESULTS: Later achievement of standing with assistance predicted lower BDI-2 scores in singletons in adjusted models (B per SD of age at achievement, -21.9 [95% confidence interval (CI), -41.5 to -2.2]). Post hoc analysis on age of standing with assistance showed that associations were driven by differences in adaptive skills (B = -5.3 [95% CI, -9.0 to -1.6]) and cognitive skills (B = -5.9 [95% CI, 11.5 to -0.4]). Analyses restricted to twins suggested no association between the age at achievement of milestones and total BDI-2 score after adjustment for gestational age and birth weight. CONCLUSIONS: This study provides evidence that the age of achieving motor milestones may be an important basis for various aspects of later child development. In twins, key predictors of later development (eg, perinatal factors) overshadow the predictive role of milestones in infancy. PMID- 27354458 TI - Use of Performance-Enhancing Substances. AB - Performance-enhancing substances (PESs) are used commonly by children and adolescents in attempts to improve athletic performance. More recent data reveal that these same substances often are used for appearance-related reasons as well. PESs include both legal over-the-counter dietary supplements and illicit pharmacologic agents. This report reviews the current epidemiology of PES use in the pediatric population, as well as information on those PESs in most common use. Concerns regarding use of legal PESs include high rates of product contamination, correlation with future use of anabolic androgenic steroids, and adverse effects on the focus and experience of youth sports participation. The physical maturation and endogenous hormone production that occur in adolescence are associated with large improvements in strength and athletic performance. For most young athletes, PES use does not produce significant gains over those seen with the onset of puberty and adherence to an appropriate nutrition and training program. PMID- 27354459 TI - Suicide and Suicide Attempts in Adolescents. AB - Suicide is the second leading cause of death for adolescents 15 to 19 years old. This report updates the previous statement of the American Academy of Pediatrics and is intended to assist pediatricians, in collaboration with other child and adolescent health care professionals, in the identification and management of the adolescent at risk for suicide. Suicide risk can only be reduced, not eliminated, and risk factors provide no more than guidance. Nonetheless, care for suicidal adolescents may be improved with the pediatrician's knowledge, skill, and comfort with the topic, as well as ready access to appropriate community resources and mental health professionals. PMID- 27354461 TI - Facile synthesis of hierarchical gold nanostructures and their catalytic application. AB - We demonstrate a one-step, surfactant-free method to prepare gold (Au) nanostructures using a synthesized aniline (ANI) derivative N-(3-amidino)-aniline (NAAN) as a reducing agent. By simply mixing NAAN with a Au precursor, raspberry like Au particles (RSPs) were formed. The presence of Ag(+) resulted in the formation of Au nanoflowers (AuNFs). The size and shape of the AuNFs can be tuned by the reaction conditions such as the NAAN/HAuCl4 ratio, the temperature and the solvent composition. Under the same reaction conditions, bowling-pin-like particles (BPLPs) were reported for the first time using commercial ANI as a reducing agent. The AuNFs exhibited good ability to oxidize peroxidase substrate 3, 3', 5, 5'-tetramethylbenzidine (TMB) by H2O2, allowing them as a peroxidase mimetic. PMID- 27354460 TI - INSIGHT Responsive Parenting Intervention and Infant Sleep. AB - OBJECTIVES: Inadequate sleep during infancy is associated with adverse outcomes for infants and families. We sought to improve sleep behaviors and duration through a responsive parenting (RP) intervention designed for obesity prevention. METHODS: The Intervention Nurses Start Infants Growing on Healthy Trajectories (INSIGHT) study is a randomized trial comparing a RP intervention with a safety control. Primiparous mother-newborn dyads were randomized after childbirth, and research nurses delivered intervention content at home visits at infant ages 3, 16, 28, and 40 weeks and at a research center visit at 1 year. The RP sleep component included developmentally appropriate messages about bedtime routines, sleep location and behaviors, and responses to wakings. Portions of the Brief Infant Sleep Questionnaire were administered 2, 8, and 52 weeks after birth with expanded sleep-related data collection at 16 and 40 weeks. RESULTS: Two hundred and seventy-nine dyads completed the first home visit; 90.7% completed the 1-year visit. Compared with controls, RP group infants were less likely to have prolonged bedtime routines >45 minutes and more likely to have earlier bedtimes at 16 and 40 weeks. They were less likely to be fed immediately before bed and more likely to self-soothe to sleep. At 8, 16, and 40 weeks, RP group nocturnal sleep duration was longer by 35, 25, and 22 minutes, respectively (P < .05 for all). Sleep duration at 1 year was similar between groups. CONCLUSIONS: The INSIGHT RP intervention positively influenced developmentally appropriate bedtime routines, sleep-related behaviors, and sleep duration for infants. PMID- 27354462 TI - Lead extraction technology and techniques: a surgeon's perspective. AB - Transvenous lead extraction procedures have gained substantial clinical importance during the past decade. With current tools and techniques, high success rates in combination with low complication rates can be achieved by experienced centres. Even in experienced hands, life-threatening complications can occur, and every physician performing such procedures must be prepared for this scenario. This necessitates immediately available access to extracorporeal circulation, and if the operator is a cardiologist, cardiac surgical standby is mandatory. PMID- 27354463 TI - Spread through air spaces is a predictive factor of recurrence and a prognostic factor in stage I lung adenocarcinoma. AB - OBJECTIVES: Spread through air spaces (STAS) is considered a prognosticator related to local recurrence. We assessed the prognostic impact of spread through air spaces and local recurrence in stage I lung adenocarcinoma. METHODS: From July 2004 to November 2014, 877 lung cancer patients underwent surgery, of whom 318 with pathological stage I adenocarcinoma were reviewed. We investigated the characteristics of spread through air spaces and analysed the relationship between spread through air spaces and prognosis. RESULTS: The median follow-up was 30 months. Of the 318 patients, 47 (14.8%) had spread through air spaces. The patients with spread through air spaces were associated with male sex (P < 0.001), smoking (P < 0.001), solid nodules (P < 0.001), stage IB disease (P = 0.006), epidermal growth factor receptor mutation negativity (P < 0.001), and lymphovascular (P < 0.001) and pleural invasion (P = 0.001). Among the preoperative findings, spread through air spaces was significantly related to solid nodules on computed tomography. Local recurrence occurred in 11 of 47 (23.4%) cases with spread through air spaces and 10 of 271 (3.7%) cases without spread through air spaces (P < 0.01). Univariate analysis showed that the overall 5-year survival rates were 62.7 and 91.1% in cases with and without spread through air spaces, respectively (P < 0.01), and the recurrence-free 5-year survival rates were 54.4 and 87.8% in cases with and without spread through air spaces, respectively (P < 0.01). Multivariate analysis confirmed spread through air spaces as a significant prognosticator for overall survival and a predictive factor for recurrence after surgery. CONCLUSIONS: Among stage I lung adenocarcinoma patients, spread through air spaces was found frequently in the invasive cases and was closely related to poor prognosis and recurrence. PMID- 27354464 TI - Split-graft technique in neonatal heart transplant for aortic atresia. AB - We describe a neonate with aortic atresia and hypoplastic aorta, listed for heart transplant after extracorporeal membrane oxygenation resuscitation and ductal stenting. The donor aorta was detached from the graft, after an isolated arch reconstruction prior to the transplant itself in a routine fashion. To the best of our knowledge, this is the first reported case of neonatal arch reconstruction before transplantation performed with grafts from the same donor in a split-way strategy. PMID- 27354465 TI - Totally endoscopic robotic repair of coronary sinus atrial septal defect. AB - Coronary sinus atrial septal defect is a rare congenital cardiac anomaly in adults. Patients with this anomaly are generally treated using conventional sternotomy or thoracotomy incisions. However, robotic surgery can be a feasible alternative in this anomaly. We report an adult patient, who presented with coronary sinus atrial septal defect. A totally endoscopic robotic repair was successfully done through a right atriotomy approach in this patient. PMID- 27354466 TI - Selective, segmental decalcification: a safe alternative to extensive debridement of a severely calcified annulus during repair of mitral regurgitation. AB - Resection of the calcium bar and creation of a more compressible annulus with pericardium are necessary in case of extensive calcification of the mitral valve annulus in patients with advanced myxomatous degenerative disease. Such annular bar calcification is technically challenging and represents a risk factor for death following mitral valve operations, because of atrio-ventricular rupture or encroachment of the coronary arteries. We describe a safe limited segmental annular debridement away from the coronary arteries that allows enough flexibility of the remaining calcified annulus to perform reduction annuloplasty in a young female patient with severe mitral regurgitation and a highly dilated and severely calcified mitral annulus. PMID- 27354467 TI - Repair of adult aortic coarctation by resection and interposition grafting. AB - OBJECTIVES: Aortic coarctation presenting during adult life most frequently represents cases of re-coarctation, following previous transcatheter or surgical therapy, or missed cases of native coarctation. In the area of evolving endovascular therapy, we believe that there is still a place for durable open repair by means of resection and interposition grafting. We, therefore, evaluated our results in adult patients with primary aortic coarctation or complications of a previous coarctation repair. METHODS: A total of 38 patients were operated between 1989 and 2014. Median age was 43 years (range 18-69 years), and 20 were male (52.6%). Seventeen patients (44.7%) had recurrent coarctation or dilatation after previous repair during childhood; the remaining 21 (55.3%) had primary coarctation diagnosed at adult age. Data were retrospectively reviewed and analysed for indications, type of repair, operative details and outcomes. RESULTS: Resection and interposition grafting was performed primarily with the use of left-left bypass (mean cross-clamping time 41 +/- 13 min). There were no in-hospital deaths, stroke, spinal cord ischaemia, renal or respiratory failure. No patient had evidence of symptomatic aortic re-coarctation or pseudoaneurysm formation on follow-up. Long-term survival after 20 years was 94.7%. CONCLUSIONS: Open surgical repair of primary, recurrent or complicated adult aortic coarctation by interposition grafting is a safe and feasible therapeutic option, providing durable long-term results and excellent long-term survival. PMID- 27354468 TI - BRAF V600E Mutant Colorectal Cancer Subtypes Based on Gene Expression. AB - PURPOSE: Mutation of BRAF at the valine 600 residue occurs in approximately 10% of colorectal cancers, a group with particularly poor prognosis. The response of BRAF mutant colorectal cancer to recent targeted strategies such as anti-BRAF or combinations with MEK and EGFR inhibitors remains limited and highly heterogeneous within BRAF V600E cohorts. There is clearly an unmet need in understanding the biology of BRAF V600E colorectal cancers and potential subgroups within this population. EXPERIMENTAL DESIGN: In the biggest yet reported cohort of 218 BRAF V600E with gene expression data, we performed unsupervised clustering using non-negative matrix factorization to identify gene expression-based subgroups and characterized pathway activation. RESULTS: We found strong support for a split into two distinct groups, called BM1 and BM2. These subtypes are independent of MSI status, PI3K mutation, gender, and sidedness. Pathway analyses revealed that BM1 is characterized by KRAS/AKT pathway activation, mTOR/4EBP deregulation, and EMT whereas BM2 displays important deregulation of the cell cycle. Proteomics data validated these observations as BM1 is characterized by high phosphorylation levels of AKT and 4EBP1, and BM2 patients display high CDK1 and low cyclin D1 levels. We provide a global assessment of gene expression motifs that differentiate BRAF V600E subtypes from other colorectal cancers. CONCLUSIONS: We suggest that BRAF mutant patients should not be considered as having a unique biology and provide an in depth characterization of heterogeneous motifs that may be exploited for drug targeting. Clin Cancer Res; 23(1); 104-15. (c)2016 AACR. PMID- 27354469 TI - CTLA-4 Limits Anti-CD20-Mediated Tumor Regression. AB - PURPOSE: The inhibition of tumor growth by anti-CD20 antibody (Ab) treatment is mediated by Ab- and complement-dependent cytotoxicity in xenograft tumor models. In addition, anti-CD20 therapy for B-cell lymphoma can result in intrinsic and extrinsic tumor resistance to further Ab treatment. However, adaptive immune response-related resistance has not been well studied in anti-CD20-mediated tumor control, and adaptive immunity has long been underestimated. The purpose of this study was to explore whether T cells are involved in mediating the effects of anti-CD20 therapy and what factors contribute to adaptive immune response-related resistance. EXPERIMENTAL DESIGN: Using a syngeneic mouse B-cell lymphoma model, we investigated the role of CD8+ T cells in anti-CD20-mediated tumor regression. Furthermore, we revealed how the tumor-specific T-cell response was initiated by anti-CD20. Finally, we studied adaptive immune response-related resistance in advanced B-cell lymphoma. RESULTS: CD8+ T cells played an essential role in anti CD20-mediated tumor regression. Mechanistically, anti-CD20 therapy promoted dendritic cell (DC)-mediated cross-presentation. Importantly, macrophages were also necessary for the increase in the tumor-specific CTL response after anti CD20 treatment, via the production of type I IFN to activate DC function. Furthermore, adaptive resistance is gradually developed through the CTLA-4 pathway in Treg cells in larger lymphomas. Further blockade of CTLA-4 can synergize with anti-CD20 treatment in antitumor activities. CONCLUSIONS: The therapeutic function of anti-CD20 depends on tumor-specific CD8+ T-cell responses initiated by anti-CD20 through macrophages and DCs. CTLA-4 blockade can synergize with anti-CD20 to overcome adaptive immune response-related resistance in advanced B-cell lymphoma. Clin Cancer Res; 23(1); 193-203. (c)2016 AACR. PMID- 27354470 TI - A Strong B-cell Response Is Part of the Immune Landscape in Human High-Grade Serous Ovarian Metastases. AB - PURPOSE: In high-grade serous ovarian cancer (HGSOC), higher densities of both B cells and the CD8+ T-cell infiltrate were associated with a better prognosis. However, the precise role of B cells in the antitumor response remains unknown. As peritoneal metastases are often responsible for relapse, our aim was to characterize the role of B cells in the antitumor immune response in HGSOC metastases. EXPERIMENTAL DESIGN: Unmatched pre and post-chemotherapy HGSOC metastases were studied. B-cell localization was assessed by immunostaining. Their cytokines and chemokines were measured by a multiplex assay, and their phenotype was assessed by flow cytometry. Further in vitro and in vivo assays highlighted the role of B cells and plasma cell IgGs in the development of cytotoxic responses and dendritic cell activation. RESULTS: B cells mainly infiltrated lymphoid structures in the stroma of HGSOC metastases. There was a strong B-cell memory response directed at a restricted repertoire of antigens and production of tumor-specific IgGs by plasma cells. These responses were enhanced by chemotherapy. Interestingly, transcript levels of CD20 correlated with markers of immune cytolytic responses and immune complexes with tumor-derived IgGs stimulated the expression of the costimulatory molecule CD86 on antigen presenting cells. A positive role for B cells in the antitumor response was also supported by B-cell depletion in a syngeneic mouse model of peritoneal metastasis. CONCLUSIONS: Our data showed that B cells infiltrating HGSOC omental metastases support the development of an antitumor response. Clin Cancer Res; 23(1); 250-62. (c)2016 AACR. PMID- 27354471 TI - An Expression Signature as an Aid to the Histologic Classification of Non-Small Cell Lung Cancer. AB - PURPOSE: Most non-small cell lung cancers (NSCLC) are now diagnosed from small specimens, and classification using standard pathology methods can be difficult. This is of clinical relevance as many therapy regimens and clinical trials are histology dependent. The purpose of this study was to develop an mRNA expression signature as an adjunct test for routine histopathologic classification of NSCLCs. EXPERIMENTAL DESIGN: A microarray dataset of resected adenocarcinomas (ADC) and squamous cell carcinomas (SCC) was used as the learning set for an ADC SCC signature. The Cancer Genome Atlas (TCGA) lung RNAseq dataset was used for validation. Another microarray dataset of ADCs and matched nonmalignant lung was used as the learning set for a tumor versus nonmalignant signature. The classifiers were selected as the most differentially expressed genes and sample classification was determined by a nearest distance approach. RESULTS: We developed a 62-gene expression signature that contained many genes used in immunostains for NSCLC typing. It includes 42 genes that distinguish ADC from SCC and 20 genes differentiating nonmalignant lung from lung cancer. Testing of the TCGA and other public datasets resulted in high prediction accuracies (93%-95%). In addition, a prediction score was derived that correlates both with histologic grading and prognosis. We developed a practical version of the Classifier using the HTG EdgeSeq nuclease protection-based technology in combination with next generation sequencing that can be applied to formalin-fixed paraffin-embedded (FFPE) tissues and small biopsies. CONCLUSIONS: Our RNA classifier provides an objective, quantitative method to aid in the pathologic diagnosis of lung cancer. Clin Cancer Res; 22(19); 4880-9. (c)2016 AACR. PMID- 27354472 TI - Hsp90 Inhibitor Ganetespib Sensitizes Non-Small Cell Lung Cancer to Radiation but Has Variable Effects with Chemoradiation. AB - PURPOSE: HSP90 inhibition is well known to sensitize cancer cells to radiation. However, it is currently unknown whether additional radiosensitization could occur in the more clinically relevant setting of chemoradiation (CRT). We used the potent HSP90 inhibitor ganetespib to determine whether it can enhance CRT effects in NSCLC. EXPERIMENTAL DESIGN: We first performed in vitro experiments in various NSCLC cell lines combining radiation with or without ganetespib. Some of these experiments included clonogenic survival assay, DNA damage repair, and cell cycle analysis, and reverse-phase protein array. We then determined whether chemotherapy affected ganetespib radiosensitization by adding carboplatin paclitaxel to some of the in vitro and in vivo xenograft experiments. RESULTS: Ganetespib significantly reduced radiation clonogenic survival in a number of lung cancer cell lines, and attenuated DNA damage repair with irradiation. Radiation caused G2-M arrest that was greatly accentuated by ganetespib. Ganetespib with radiation also dose-dependently upregulated p21 and downregulated pRb levels that were not apparent with either drug or radiation alone. However, when carboplatin-paclitaxel was added, ganetespib was only able to radiosensitize some cell lines but not others. This variable in vitro CRT effect was confirmed in vivo using xenograft models. CONCLUSIONS: Ganetespib was able to potently sensitize a number of NSCLC cell lines to radiation but has variable effects when added to platinum-based doublet CRT. For optimal clinical translation, our data emphasize the importance of preclinical testing of drugs in the context of clinically relevant therapy combinations. Clin Cancer Res; 22(23); 5876-86. (c)2016 AACR. PMID- 27354474 TI - Shorter Remission Telomere Length Predicts Delayed Neutrophil Recovery After Acute Myeloid Leukemia Therapy: A Report From the Children's Oncology Group. AB - Purpose Suboptimal outcomes for children with acute myeloid leukemia (AML) necessitate maximally intensive therapy. Consequently, serious adverse events, such as prolonged periods of profound myelosuppression, contribute to AML treatment-related mortality. Telomeres, the repetitive DNA-protein structures at chromosome ends, influence cellular replicative capacity in that critically short telomeres can induce cell senescence or apoptosis. Our objective was to evaluate the impact of telomere length on duration of post-therapy neutropenia in a pediatric AML cohort. Patients and Methods Patients were diagnosed with de novo AML, enrolled in Children's Oncology Group study AAML0531, and included those with (n = 53) and without (n = 62) significantly delayed neutrophil recovery after chemotherapy. We used quantitative polymerase chain reaction to measure telomere content (TC), a validated proxy for telomere length, from remission bone marrow samples obtained after the second induction chemotherapy course. Results Less TC was significantly associated with prolonged neutropenia after the fourth ( P < .001) and fifth chemotherapy courses ( P = .002). Cox regression adjusting for age at diagnosis confirmed that TC remained independently predictive of time to recovery of absolute neutrophil count for both the fourth and fifth courses ( P = .002 and .009, respectively). DNA from patients was analyzed for germline mutations in four telomere maintenance genes associated with telomere biology disorders. Sequence analysis revealed no enrichment of rare or novel variants in the delayed recovery group. Conclusion Our results suggest that TC at end of AML induction is associated with hematopoietic reconstitution capacity independently of age and may identify those at highest risk for markedly delayed bone marrow recovery after AML therapy. PMID- 27354473 TI - Tumor-Derived CCL2 Mediates Resistance to Radiotherapy in Pancreatic Ductal Adenocarcinoma. AB - PURPOSE: Local tumor growth is a major cause of morbidity and mortality in nearly 30% of patients with pancreatic ductal adenocarcinoma (PDAC). Radiotherapy is commonly used for local disease control in PDAC, but its efficacy is limited. We studied the impact of selectively intervening on radiotherapy-induced inflammation as an approach to overcome resistance to radiotherapy in PDAC. EXPERIMENTAL DESIGN: PDAC cell lines derived from primary pancreatic tumors arising spontaneously in KrasLSL-G12D/+;Trp53LSL-R172H/+;Pdx-1 Cre mice were implanted into syngeneic mice and tumors were focally irradiated using the Small Animal Radiation Research Platform (SARRP). We determined the impact of depleting T cells and Ly6C+ monocytes as well as inhibiting the chemokine CCL2 on radiotherapy efficacy. Tumors were analyzed by flow cytometry and IHC to detect changes in leukocyte infiltration, tumor viability, and vascularity. Assays were performed on tumor tissues to detect cytokines and gene expression. RESULTS: Ablative radiotherapy alone had minimal impact on PDAC growth but led to a significant increase in CCL2 production by tumor cells and recruitment of Ly6C+CCR2+ monocytes. A neutralizing anti-CCL2 antibody selectively inhibited radiotherapy-dependent recruitment of monocytes/macrophages and delayed tumor growth but only in combination with radiotherapy (P < 0.001). This antitumor effect was associated with decreased tumor proliferation and vascularity. Genetic deletion of CCL2 in PDAC cells also improved radiotherapy efficacy. CONCLUSIONS: PDAC responds to radiotherapy by producing CCL2, which recruits Ly6C+CCR2+ monocytes to support tumor proliferation and neovascularization after radiotherapy. Disrupting the CCL2-CCR2 axis in combination with radiotherapy holds promise for improving radiotherapy efficacy in PDAC. Clin Cancer Res; 23(1); 137-48. (c)2016 AACR. PMID- 27354475 TI - Reining in the Excessive Use of Medical Tests: What Are the Next Steps? PMID- 27354476 TI - Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. AB - Purpose Classical Hodgkin lymphoma (HL) frequently exhibits genetic alterations leading to overexpression of the programmed death-1 (PD-1) ligands, suggesting a possible vulnerability to PD-1 blockade. The phase Ib study KEYNOTE-013 (NCT01953692) tested the safety and efficacy of the anti-PD-1 antibody pembrolizumab in patients with hematologic malignancies. Based on its genetics, HL was included as an independent cohort. Methods We enrolled patients with relapsed or refractory HL whose disease progressed on or after treatment with brentuximab vedotin. Patients received pembrolizumab, 10 mg/kg every 2 weeks, until disease progression occurred. Response to treatment was assessed at week 12 and every 8 weeks thereafter. Principal end points were safety and complete remission (CR) rate. Results Thirty-one patients were enrolled; 55% had more than four lines of prior therapy, and 71% had relapsed after autologous stem cell transplantation. Five patients (16%) experienced grade 3 drug-related adverse events (AEs); there were no grade 4 AEs or deaths related to treatment. The CR rate was 16% (90% CI, 7% to 31%). In addition, 48% of patients achieved a partial remission, for an overall response rate of 65% (90% CI, 48% to 79%). Most of the responses (70%) lasted longer than 24 weeks (range, 0.14+ to 74+ weeks), with a median follow-up of 17 months. The progression-free survival rate was 69% at 24 weeks and 46% at 52 weeks. Biomarker analyses demonstrated a high prevalence of PD-L1 and PD-L2 expression, treatment-induced expansion of T cells and natural killer cells, and activation of interferon-gamma, T-cell receptor, and expanded immune-related signaling pathways. Conclusions Pembrolizumab was associated with a favorable safety profile. Pembrolizumab treatment induced favorable responses in a heavily pretreated patient cohort, justifying further studies. PMID- 27354477 TI - Association Between Plasma Genotyping and Outcomes of Treatment With Osimertinib (AZD9291) in Advanced Non-Small-Cell Lung Cancer. AB - PURPOSE: Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated potent activity against TKI resistance mediated by EGFR T790M. We studied whether noninvasive genotyping of cell-free plasma DNA (cfDNA) is a useful biomarker for prediction of outcome from a third generation EGFR-TKI, osimertinib. METHODS: Plasma was collected from all patients in the first-in-man study of osimertinib. Patients who were included had acquired EGFR-TKI resistance and evidence of a common EGFR-sensitizing mutation. Genotyping of cell-free plasma DNA was performed by using BEAMing. Plasma genotyping accuracy was assessed by using tumor genotyping from a central laboratory as reference. Objective response rate (ORR) and progression-free survival (PFS) were analyzed in all T790M-positive or T790M-negative patients. RESULTS: Sensitivity of plasma genotyping for detection of T790M was 70%. Of 58 patients with T790M-negative tumors, T790M was detected in plasma of 18 (31%). ORR and median PFS were similar in patients with T790M-positive plasma (ORR, 63%; PFS, 9.7 months) or T790M-positive tumor (ORR, 62%; PFS, 9.7 months) results. Although patients with T790M-negative plasma had overall favorable outcomes (ORR, 46%; median PFS, 8.2 months), tumor genotyping distinguished a subset of patients positive for T790M who had better outcomes (ORR, 69%; PFS, 16.5 months) as well as a subset of patients negative for T790M with poor outcomes (ORR, 25%; PFS, 2.8 months). CONCLUSION: In this retrospective analysis, patients positive for T790M in plasma have outcomes with osimertinib that are equivalent to patients positive by a tissue-based assay. This study suggests that, upon availability of validated plasma T790M assays, some patients could avoid a tumor biopsy for T790M genotyping. As a result of the 30% false-negative rate of plasma genotyping, those with T790M-negative plasma results still need a tumor biopsy to determine presence or absence of T790M. PMID- 27354479 TI - Long Day's Journey Into Night for Lower-Risk Myelodysplastic Syndromes. PMID- 27354478 TI - Comprehensive Audiometric Analysis of Hearing Impairment and Tinnitus After Cisplatin-Based Chemotherapy in Survivors of Adult-Onset Cancer. AB - PURPOSE: Cisplatin is widely used but highly ototoxic. Effects of cumulative cisplatin dose on hearing loss have not been comprehensively evaluated in survivors of adult-onset cancer. PATIENTS AND METHODS: Comprehensive audiological measures were conducted on 488 North American male germ cell tumor (GCT) survivors in relation to cumulative cisplatin dose, including audiograms (0.25 to 12 kHz), tests of middle ear function, and tinnitus. American Speech-Language Hearing Association criteria defined hearing loss severity. The geometric mean of hearing thresholds (0.25 to 12 kHz) summarized overall hearing status consistent with audiometric guidelines. Patients were sorted into quartiles of hearing thresholds of age- and sex-matched controls. RESULTS: Increasing cumulative cisplatin dose (median, 400 mg/m(2); range, 200 to 800 mg/m(2)) was significantly related to hearing loss at 4, 6, 8, 10, and 12 kHz (P trends, .021 to < .001): every 100 mg/m(2) increase resulted in a 3.2-dB impairment in age-adjusted overall hearing threshold (4 to 12 kHz; P < .001). Cumulative cisplatin doses > 300 mg/m(2) were associated with greater American Speech-Language-Hearing Association-defined hearing loss severity (odds ratio, 1.59; P = .0066) and worse normative-matched quartiles (odds ratio, 1.33; P = .093) compared with smaller doses. Almost one in five (18%) patients had severe to profound hearing loss. Tinnitus (40% patients) was significantly correlated with reduced hearing at each frequency (P < .001). Noise-induced damage (10% patients) was unaffected by cisplatin dose (P = .59). Hypertension was significantly related (P = .0066) to overall hearing threshold (4 to 12 kHz) in age- and cisplatin dose-adjusted analyses. Middle ear deficits occurred in 22.3% of patients but, as expected, were not related to cytotoxic drug dosage. CONCLUSION: Follow-up of adult-onset cancer survivors given cisplatin should include routine inquiry for hearing status and tinnitus, referral to audiologists as clinically indicated, and hypertension control. Patients should be urged to avoid noise exposure, ototoxic drugs, and other factors that further damage hearing. PMID- 27354480 TI - Randomized Phase III Study of Lenalidomide Versus Placebo in RBC Transfusion Dependent Patients With Lower-Risk Non-del(5q) Myelodysplastic Syndromes and Ineligible for or Refractory to Erythropoiesis-Stimulating Agents. AB - PURPOSE: This international phase III, randomized, placebo-controlled, double blind study assessed the efficacy and safety of lenalidomide in RBC transfusion dependent patients with International Prognostic Scoring System lower-risk non del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis stimulating agents. PATIENTS AND METHODS: In total, 239 patients were randomly assigned (2:1) to treatment with lenalidomide (n = 160) or placebo (n = 79) once per day (on 28-day cycles). The primary end point was the rate of RBC transfusion independence (TI) >= 8 weeks. Secondary end points were RBC-TI >= 24 weeks, duration of RBC-TI, erythroid response, health-related quality of life (HRQoL), and safety. RESULTS: RBC-TI >= 8 weeks was achieved in 26.9% and 2.5% of patients in the lenalidomide and placebo groups, respectively (P < .001). Ninety percent of patients achieving RBC-TI responded within 16 weeks of treatment. Median duration of RBC-TI with lenalidomide was 30.9 weeks (95% CI, 20.7 to 59.1). Transfusion reduction of >= 4 units packed RBCs, on the basis of a 112-day assessment, was 21.8% in the lenalidomide group and 0% in the placebo group. Higher response rates were observed in patients with lower baseline endogenous erythropoietin <= 500 mU/mL (34.0% v 15.5% for > 500 mU/mL). At week 12, mean changes in HRQoL scores from baseline did not differ significantly between treatment groups, which suggests that lenalidomide did not adversely affect HRQoL. Achievement of RBC-TI >= 8 weeks was associated with significant improvements in HRQoL (P < .01). The most common treatment-emergent adverse events were neutropenia and thrombocytopenia. CONCLUSION: Lenalidomide yields sustained RBC-TI in 26.9% of RBC transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents. Response to lenalidomide was associated with improved HRQoL. Treatment-emergent adverse event data were consistent with the known safety profile of lenalidomide. PMID- 27354481 TI - Nivolumab in Combination With Platinum-Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. AB - PURPOSE: Nivolumab, a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody, has demonstrated improved survival in previously treated patients with advanced non-small-cell lung cancer (NSCLC). CheckMate 012, a phase I, multicohort study, was conducted to explore the safety and efficacy of nivolumab as monotherapy or combined with current standard therapies in first line advanced NSCLC. Here, we report results for nivolumab plus platinum-based doublet chemotherapy (PT-DC). PATIENTS AND METHODS: Patients (N = 56) received nivolumab (intravenously) plus PT-DC concurrently every 3 weeks for four cycles followed by nivolumab alone until progression or unacceptable toxicity. Regimens were nivolumab 10 mg/kg plus gemcitabine-cisplatin (squamous) or pemetrexed cisplatin (nonsquamous) or nivolumab 5 or 10 mg/kg plus paclitaxel-carboplatin (all histologies). The primary objective was to assess safety and tolerability. Secondary objectives included objective response rate and 24-week progression free survival rate (per Response Evaluation Criteria in Solid Tumors version 1.1); exploratory objectives included overall survival (OS) and response by tumor programmed death ligand-1 expression. RESULTS: No dose-limiting toxicities occurred during the first 6 weeks of treatment. Forty-five percent of patients (25 of 56 patients) reported grade 3 or 4 treatment-related adverse events (AEs); 7% of patients (n = 4) had pneumonitis. Twenty-one percent of patients (n = 12) discontinued all study therapy as a result of treatment-related AEs. Objective response rates for nivolumab 10 mg/kg plus gemcitabine-cisplatin, nivolumab 10 mg/kg plus pemetrexed-cisplatin, nivolumab 10 mg/kg plus paclitaxel-carboplatin, and nivolumab 5 mg/kg plus paclitaxel-carboplatin were 33%, 47%, 47%, and 43%, respectively; 24-week progression-free survival rates were 51%, 71%, 38%, and 51%, respectively; 2-year OS rates were 25%, 33%, 27%, and 62%, respectively. Responses were achieved regardless of tumor programmed death ligand-1 expression. CONCLUSION: The safety profile of nivolumab plus PT-DC was consistent with that expected for individual agents; however, treatment discontinuation related to AEs was greater with the combination. Encouraging activity was observed, especially for the nivolumab 5 mg/kg plus paclitaxel-carboplatin group, with a 2-year OS rate of 62%. PMID- 27354482 TI - From Illumination to Innovation: Visualizing the Future-The 2015 Presidential Address. PMID- 27354483 TI - Differential Crizotinib Response Duration Among ALK Fusion Variants in ALK Positive Non-Small-Cell Lung Cancer. AB - PURPOSE: Anaplastic lymphoma kinase (ALK) rearrangement-positive non-small-cell lung cancers can be effectively treated with an ALK tyrosine kinase inhibitor (TKI) such as crizotinib, but the response magnitude and duration are heterogeneous. Several ALK variants have been identified, but few studies have focused on the effects of different ALK variants on the efficacy of crizotinib. PATIENTS AND METHODS: Among 55 patients treated with crizotinib as the initial ALK-TKI between January 2007 and December 2014, we identified 35 patients with tumor specimens that could be evaluated for ALK variants by reverse transcription polymerase chain reaction. We retrospectively evaluated the efficacy of crizotinib on the basis of the objective response rate and progression-free survival (PFS) according to the ALK variants. RESULTS: The most frequent ALK variant was variant 1 in 19 patients (54%), followed by variant 2 in five patients (14%), variant 3a/3b in four patients (12%), and other variants in seven patients (20%). Objective response rate was 69% in all patients, whereas it was 74% and 63% in the variant 1 and non-variant 1 groups, respectively. The median PFS time was significantly longer in patients with variant 1 than in those with non-variant 1 (median PFS, 11.0 months [95% CI, 6.5 to 43.0 months] v 4.2 months [95% CI, 1.6 to 10.2 months], respectively; P < .05). Multivariable analysis identified two significant factors associated with PFS duration, ALK variant 1 (hazard ratio, 0.350; 95% CI, 0.128 to 0.929; P < .05) and advanced stage (hazard ratio, 4.646; 95% CI, 1.381 to 21.750; P < .05). CONCLUSION: Our results indicate the better efficacy of crizotinib in patients with ALK variant 1 versus non variant 1. The ALK variant status might affect the efficacy of ALK-TKIs. PMID- 27354484 TI - Quality of Life in Patients With Advanced Cancer: Differential Association With Performance Status and Systemic Inflammatory Response. AB - PURPOSE: Quality of life is a key component of cancer care; however, the factors that determine quality of life are not well understood. The aim of this study was to examine the relationship between quality of life parameters, performance status (PS), and the systemic inflammatory response in patients with advanced cancer. METHODS: An international biobank of patients with advanced cancer was analyzed. Quality of life was assessed at a single time point by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ-C30). PS was assessed by using the Eastern Cooperative Oncology Group (ECOG) classification. Systemic inflammation was assessed by using the modified Glasgow Prognostic Score (mGPS), which combines C reactive protein and albumin. The relationship between quality of life parameters, ECOG PS, and the mGPS was examined. RESULTS: Data were available for 2,520 patients, and the most common cancers were GI (585 patients [22.2%]) and pulmonary (443 patients [17.6%]). The median survival was 4.25 months (interquartile range, 1.36 to 12.9 months). Increasing mGPS (systemic inflammation) and deteriorating PS were associated with deterioration in quality of-life parameters (P < .001). Increasing systemic inflammation was associated with deterioration in quality-of-life parameters independent of PS. CONCLUSION: Systemic inflammation was associated with quality-of-life parameters independent of PS in patients with advanced cancer. Further investigation of these relationships in longitudinal studies and investigations of possible effects of attenuating systemic inflammation are now warranted. PMID- 27354485 TI - Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. AB - PURPOSE: Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non-small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I, multicohort, Checkmate 012 trial. METHODS: Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity; postprogression treatment was permitted per protocol. The primary objective was to assess safety; secondary objectives included objective response rate (ORR) and 24-week progression-free survival (PFS) rate; overall survival (OS) was an exploratory end point. RESULTS: Any-grade treatment-related adverse events (AEs) occurred in 71% of patients, most commonly: fatigue (29%), rash (19%), nausea (14%), diarrhea (12%), pruritus (12%), and arthralgia (10%). Ten patients (19%) reported grade 3 to 4 treatment-related AEs; grade 3 rash was the only grade 3 to 4 event occurring in more than one patient (n = 2; 4%). Six patients (12%) discontinued because of a treatment-related AE. The confirmed ORR was 23% (12 of 52), including four ongoing complete responses. Nine of 12 responses (75%) occurred by first tumor assessment (week 11); eight (67%) were ongoing (range, 5.3+ to 25.8+ months) at the time of data lock. ORR was 28% (nine of 32) in patients with any degree of tumor PD-ligand 1 expression and 14% (two of 14) in patients with no PD ligand 1 expression. Median PFS was 3.6 months, and the 24-week PFS rate was 41% (95% CI, 27 to 54). Median OS was 19.4 months, and the 1-year and 18-month OS rates were 73% (95% CI, 59 to 83) and 57% (95% CI, 42 to 70), respectively. CONCLUSION: First-line nivolumab monotherapy demonstrated a tolerable safety profile and durable responses in first-line advanced NSCLC. PMID- 27354486 TI - Cellular Profiles and Molecular Mediators of Lesion Cascades in the Placode in Human Open Spinal Neural Tube Defects. AB - Myelomeningoceles (mmc) are clinically challenging CNS malformations. Although improvement in their management has been achieved with respect to antenatal diagnosis, prevention, and fetal surgery, the cellular mechanisms of damage in the neural placode are poorly understood. We aimed to identify cellular and molecular factors in lesion amplifying cascades in mmc placodes. Seventeen mmc specimens obtained during reconstructive surgery that harbored sufficient neuroepithelial tissue were investigated. Normal adult and stillborn spinal cord tissue served as controls. Placodes exhibited similar cellular profiles with consistent neuronal marker expression, elevated GFAP-/vimentin immunoreactivity in all, and CD3/CD11b/CD68-immunolabeling in some cases. Increased expression of pro-inflammatory (tumor necrosis factor, interleukin-1beta [Il-1beta]/IL-1 receptor type 1 [IL-R1]) and neuroprotective erythropoietin/erythropoietin receptor (Epo/EpoR) cytokines was detected by immunohistochemistry, double fluorescence labeling, and real-time RT-PCR. In all cases, there was a multi cellular induction of IL-1beta and IL1-R1. EpoR and Epo immunoreactivity was elevated in some cases with neuronal expression patterns. Epo was further co expressed with HIF-1/-2alpha, which paralleled Epo induction in the corresponding placodes. These observations confirm the induction of cellular and molecular alterations in human mmc placodes that resemble the secondary lesion cascades induced by spinal cord injury. The pro-inflammatory and neuroprotective cytokine expression in mmc placodes may represent new targets for the treatment of open neural tube defects. PMID- 27354487 TI - Polymicrobial biofilm formation by Candida albicans, Actinomyces naeslundii, and Streptococcus mutans is Candida albicans strain and medium dependent. AB - Oral biofilms comprise of extracellular polysaccharides and polymicrobial microorganisms. The objective of this study was to determine the effect of polymicrobial interactions of Candida albicans, Actinomyces naeslundii, and Streptococcus mutans on biofilm formation with the hypotheses that biofilm biomass and metabolic activity are both C. albicans strain and growth medium dependent. To study monospecific biofilms, C. albicans, A. naeslundii, and S. mutans were inoculated into artificial saliva medium (ASM) and RPMI-1640 in separate vials, whereas to study polymicrobial biofilm formation, the inoculum containing microorganisms was prepared in the same vial prior inoculation into a 96-well plate followed by 72 hours incubation. Finally, biofilm biomass and metabolic activity were measured using crystal violet and XTT assays, respectively. Our results showed variability of monospecies and polymicrobial biofilm biomass between C. albicans strains and growth medium. Based on cut-offs, out of 32, seven RPMI-grown biofilms had high biofilm biomass (HBB), whereas, in ASM-grown biofilms, 14 out of 32 were HBB. Of the 32 biofilms grown in RPMI-1640, 21 were high metabolic activity (HMA), whereas in ASM, there was no biofilm had HMA. Significant differences were observed between ASM and RPMI-grown biofilms with respect to metabolic activity (P <01). In conclusion, biofilm biomass and metabolic activity were both C. albicans strain and growth medium dependent. PMID- 27354488 TI - Culturable fungi in potting soils and compost. AB - In the present study the spectrum and the incidence of fungi in potting soils and compost was investigated. Since soil is one of the most important biotopes for fungi, relatively high concentrations of fungal propagules are to be expected. For detection of fungi, samples of commercial soils, compost and soils from potted plants (both surface and sub-surface) were suspended and plated onto several mycological media. The resulting colonies were evaluated qualitatively and quantitatively. The results from the different sampling series vary, but concentrations on the surface of potted plants and in commercial soils are increased tenfold compared to compost and sub-surface soils. Median values range from 9.5 * 10(4) colony forming units (CFU)/g to 5.5 * 10(5) CFU/g. The spectrum of fungi also varies in the soils. However, all sampling series show high proportion of Aspergillus and Penicillium species, including potentially pathogenic species such as Aspergillus fumigatus. Cladosporium, a genus dominant in the ambient air, was found preferably in samples which were in contact with the air. The results show that potentially pathogenic fungi are present in soils. Immunocompromised individuals should avoid handling soils or potted plants in their immediate vicinity. PMID- 27354490 TI - Thoroughly modern hygiene. PMID- 27354489 TI - Antidepressant use and violent crimes among young people: a longitudinal examination of the Finnish 1987 birth cohort. AB - BACKGROUND: The use of antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), has been questioned due to poor efficacy and safety. We examined whether young violent offenders were more likely antidepressant users prior to their first violent offence than other young persons. METHODS: The study is a follow-up of children born in Finland in 1987 (n=59 120), linking national registers to each other using personal identity codes. Data on psychotropic drug use came from a register of reimbursed drugs and data on crimes from a register on court convictions (after the age of 14 years). Participants were followed until the age of 18 years, and for some analyses until the end of the follow-up (mean 21 years). To adjust for differences in background characteristics, regression analyses for antidepressant use were made, using the no-conviction group as the reference. RESULTS: Proportions of young people convicted by the age of 18 years were: 5% of boys (1.7% for violent crimes) and 1% (0.5%) of girls. Antidepressant use (both overall and for SSRIs) prior to violent crime was more common among those convicted than among those without convictions. Among boys with repeated violent crimes, it was also more common than among boys with non violent crimes. Adjustment for differences in background characteristics decreased the associations between antidepressant use and violent crime, but did not eliminate them. CONCLUSIONS: The results add further evidence for caution in prescribing antidepressants among young persons. It also calls for a reanalysis of violence measures in the original trial data. PMID- 27354491 TI - In future we are going to have to view our microbial world very differently. PMID- 27354492 TI - Diary. PMID- 27354494 TI - Holistic Approach in Preventing Spread of Infectious Diseases: A Cuban Example. PMID- 27354495 TI - Policy. PMID- 27354496 TI - e-Bug: educating children and young people on hygiene, the spread of infection and antibiotics. PMID- 27354498 TI - Lessons learned from drug design and development. PMID- 27354497 TI - Are we too clean? Reframing the hygiene hypothesis and its implications for allergies, infectious diseases and our lifestyles. PMID- 27354500 TI - Older adults' domestic kitchen practices associated with an increased risk of listeriosis. PMID- 27354499 TI - Food safety and the hygiene misnomer. PMID- 27354501 TI - Waking up from antibiotic sleep. PMID- 27354502 TI - Early life immune ontogeny - understanding how we build and sustain immunity to infection. PMID- 27354503 TI - Increasing delivery of healthcare at home and the importance of hygiene. PMID- 27354504 TI - The key role of hygiene and cleanliness in the domestic environment. PMID- 27354508 TI - Erratum. PMID- 27354509 TI - Diapause and Cold Hardiness of the Almond Wasp, Eurytoma amygdali (Hymenoptera: Eurytomidae), Two Independent Phenomena. AB - The almond wasp, Eurytoma amygdali Enderlein (Hymenoptera: Eurytomidae), a key pest of almond, is a univoltine pest diapausing as last instar larvae inside the damaged fruits for almost nine months in a year. In this study, changes in the amount of total simple sugars, lipid, protein, glycogen, trehalose, glucose, supercooling points (SCPs), and cold hardiness of the diapausing larvae were measured from October to March for first year diapause-destined and in August and September for second year diapause-destined larvae. Changes in glycogen content were reversely proportional to changes in total simple sugars and low molecular weight carbohydrates. These changes reflect the interconversion of glycogen to sugar alcohol in order to increase the insect cold tolerance. We found that cold hardiness and diapause of the last instar larvae of the almond wasp have evolved separately. Cold hardiness was highly associated with physiological changes (accumulation of cryoprotectants), but no physiological changes occurred in early diapause of first year diapause-destined and second year diapause-destined larvae. The almond wasp larvae were found to be a freeze-avoidant insect, as no larva survived after SCP determination and crystallization of its body fluids. PMID- 27354505 TI - Time to abandon the hygiene hypothesis: new perspectives on allergic disease, the human microbiome, infectious disease prevention and the role of targeted hygiene. AB - AIMS: To review the burden of allergic and infectious diseases and the evidence for a link to microbial exposure, the human microbiome and immune system, and to assess whether we could develop lifestyles which reconnect us with exposures which could reduce the risk of allergic disease while also protecting against infectious disease. METHODS: Using methodology based on the Delphi technique, six experts in infectious and allergic disease were surveyed to allow for elicitation of group judgement and consensus view on issues pertinent to the aim. RESULTS: Key themes emerged where evidence shows that interaction with microbes that inhabit the natural environment and human microbiome plays an essential role in immune regulation. Changes in lifestyle and environmental exposure, rapid urbanisation, altered diet and antibiotic use have had profound effects on the human microbiome, leading to failure of immunotolerance and increased risk of allergic disease. Although evidence supports the concept of immune regulation driven by microbe-host interactions, the term 'hygiene hypothesis' is a misleading misnomer. There is no good evidence that hygiene, as the public understands, is responsible for the clinically relevant changes to microbial exposures. CONCLUSION: Evidence suggests a combination of strategies, including natural childbirth, breast feeding, increased social exposure through sport, other outdoor activities, less time spent indoors, diet and appropriate antibiotic use, may help restore the microbiome and perhaps reduce risks of allergic disease. Preventive efforts must focus on early life. The term 'hygiene hypothesis' must be abandoned. Promotion of a risk assessment approach (targeted hygiene) provides a framework for maximising protection against pathogen exposure while allowing spread of essential microbes between family members. To build on these findings, we must change public, public health and professional perceptions about the microbiome and about hygiene. We need to restore public understanding of hygiene as a means to prevent infectious disease. PMID- 27354510 TI - Effects of Self-Superparasitism and Temperature on Biological Traits of Two Neotropical Trichogramma (Hymenoptera: Trichogrammatidae) Species. AB - It is common for a female trichogrammatid to lay more than one egg per host, a phenomenon known as self-superparasitism, which exposes her offspring to intraspecific, intrinsic competition (IIC) with its own siblings. Information about how often self-superparasitism occurs and how IIC interacts with abiotic factors is rare, especially regarding the Neotropical Trichogramma species. Here we determined the frequency of self-superparasitism in Trichogramma atopovirilia Oatman & Platner (Ta) and T. pretiosum Riley (Tp), and the effects of IIC and temperature on the sex ratio, egg-to-adulthood period, and survivorship of both species' offspring. Individual females were offered eggs of Spodoptera frugiperda (J.E. Smith) for 30 min. A group of parasitized hosts was then dissected for determination of the self-superparasitism frequency, while another group was incubated at 15, 18, 21, 24, 27, 30, and 33 degrees C. High rates of self superparasitism were found in both Ta (0.55 +/- 0.07) and Tp (0.62 +/- 0.06). IIC interacted with temperature decreasing Ta and Tp's survivorship, lengthening the egg-to-adulthood period in Tp and shortening it in Ta, and balancing Ta's sex ratio. Based on survivorship rate, Ta and Tp could not be differentiated if their immatures develop in absence of IIC. However, in its presence, Tp was 3 * more likely to survive than Ta at 33 degrees C, while at 15 degrees C Ta survived 2* better than Tp These results show that self-superparasitism can be very common in both Ta and Tp, and that its effects on the species' biological traits and competitiveness strongly depend on the IIC-temperature interaction. PMID- 27354511 TI - Detecting regional patterns of changing CO2 flux in Alaska. AB - With rapid changes in climate and the seasonal amplitude of carbon dioxide (CO2) in the Arctic, it is critical that we detect and quantify the underlying processes controlling the changing amplitude of CO2 to better predict carbon cycle feedbacks in the Arctic climate system. We use satellite and airborne observations of atmospheric CO2 with climatically forced CO2 flux simulations to assess the detectability of Alaskan carbon cycle signals as future warming evolves. We find that current satellite remote sensing technologies can detect changing uptake accurately during the growing season but lack sufficient cold season coverage and near-surface sensitivity to constrain annual carbon balance changes at regional scale. Airborne strategies that target regular vertical profile measurements within continental interiors are more sensitive to regional flux deeper into the cold season but currently lack sufficient spatial coverage throughout the entire cold season. Thus, the current CO2 observing network is unlikely to detect potentially large CO2 sources associated with deep permafrost thaw and cold season respiration expected over the next 50 y. Although continuity of current observations is vital, strategies and technologies focused on cold season measurements (active remote sensing, aircraft, and tall towers) and systematic sampling of vertical profiles across continental interiors over the full annual cycle are required to detect the onset of carbon release from thawing permafrost. PMID- 27354513 TI - Correction for Guo et al., Dominant hemisphere lateralization of cortical parasympathetic control as revealed by frontotemporal dementia. PMID- 27354512 TI - Analysis of tandem gene copies in maize chromosomal regions reconstructed from long sequence reads. AB - Haplotype variation not only involves SNPs but also insertions and deletions, in particular gene copy number variations. However, comparisons of individual genomes have been difficult because traditional sequencing methods give too short reads to unambiguously reconstruct chromosomal regions containing repetitive DNA sequences. An example of such a case is the protein gene family in maize that acts as a sink for reduced nitrogen in the seed. Previously, 41-48 gene copies of the alpha zein gene family that spread over six loci spanning between 30- and 500 kb chromosomal regions have been described in two Iowa Stiff Stalk (SS) inbreds. Analyses of those regions were possible because of overlapping BAC clones, generated by an expensive and labor-intensive approach. Here we used single molecule real-time (Pacific Biosciences) shotgun sequencing to assemble the six chromosomal regions from the Non-Stiff Stalk maize inbred W22 from a single DNA sequence dataset. To validate the reconstructed regions, we developed an optical map (BioNano genome map; BioNano Genomics) of W22 and found agreement between the two datasets. Using the sequences of full-length cDNAs from W22, we found that the error rate of PacBio sequencing seemed to be less than 0.1% after autocorrection and assembly. Expressed genes, some with premature stop codons, are interspersed with nonexpressed genes, giving rise to genotype-specific expression differences. Alignment of these regions with those from the previous analyzed regions of SS lines exhibits in part dramatic differences between these two heterotic groups. PMID- 27354514 TI - Computational and experimental investigations of one-step conversion of poly(carbonate)s into value-added poly(aryl ether sulfone)s. AB - It is estimated that ~2.7 million tons poly(carbonate)s (PCs) are produced annually worldwide. In 2008, retailers pulled products from store shelves after reports of bisphenol A (BPA) leaching from baby bottles, reusable drink bottles, and other retail products. Since PCs are not typically recycled, a need for the repurposing of the PC waste has arisen. We report the one-step synthesis of poly(aryl ether sulfone)s (PSUs) from the depolymerization of PCs and in situ polycondensation with bis(aryl fluorides) in the presence of carbonate salts. PSUs are high-performance engineering thermoplastics that are commonly used for reverse osmosis and water purification membranes, medical equipment, as well as high temperature applications. PSUs generated through this cascade approach were isolated in high purity and yield with the expected thermal properties and represent a procedure for direct conversion of one class of polymer to another in a single step. Computational investigations performed with density functional theory predict that the carbonate salt plays two important catalytic roles in this reaction: it decomposes the PCs by nucleophilic attack, and in the subsequent polyether formation process, it promotes the reaction of phenolate dimers formed in situ with the aryl fluorides present. We envision repurposing poly(BPA carbonate) for the production of value-added polymers. PMID- 27354515 TI - Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus. AB - Zika virus (ZIKV) is an emerging mosquito-borne flavivirus of significant public health concern. ZIKV shares a high degree of sequence and structural homology compared with other flaviviruses, including dengue virus (DENV), resulting in immunological cross-reactivity. Improving our current understanding of the extent and characteristics of this immunological cross-reactivity is important, as ZIKV is presently circulating in areas that are highly endemic for dengue. To assess the magnitude and functional quality of cross-reactive immune responses between these closely related viruses, we tested acute and convalescent sera from nine Thai patients with PCR-confirmed DENV infection against ZIKV. All of the sera tested were cross-reactive with ZIKV, both in binding and in neutralization. To deconstruct the observed serum cross-reactivity in depth, we also characterized a panel of DENV-specific plasmablast-derived monoclonal antibodies (mAbs) for activity against ZIKV. Nearly half of the 47 DENV-reactive mAbs studied bound to both whole ZIKV virion and ZIKV lysate, of which a subset also neutralized ZIKV. In addition, both sera and mAbs from the dengue-infected patients enhanced ZIKV infection of Fc gamma receptor (FcgammaR)-bearing cells in vitro. Taken together, these findings suggest that preexisting immunity to DENV may impact protective immune responses against ZIKV. In addition, the extensive cross-reactivity may have implications for ZIKV virulence and disease severity in DENV-experienced populations. PMID- 27354516 TI - Physiological role for amyloid precursor protein in adult experience-dependent plasticity. AB - Changes in neural circuits after experience-dependent plasticity are brought about by the formation of new circuits via axonal growth and pruning. Here, using a combination of electrophysiology, adeno-associated virus-delivered fluorescent proteins, analysis of mutant mice, and two-photon microscopy, we follow long range horizontally projecting axons in primary somatosensory cortex before and after selective whisker plucking. Whisker plucking induces axonal growth and pruning of horizontal projecting axons from neurons located in the surrounding intact whisker representations. We report that amyloid precursor protein is crucial for axonal pruning and contributes in a cell autonomous way. PMID- 27354517 TI - beta-arrestin-biased signaling through the beta2-adrenergic receptor promotes cardiomyocyte contraction. AB - beta-adrenergic receptors (betaARs) are critical regulators of acute cardiovascular physiology. In response to elevated catecholamine stimulation during development of congestive heart failure (CHF), chronic activation of Gs dependent beta1AR and Gi-dependent beta2AR pathways leads to enhanced cardiomyocyte death, reduced beta1AR expression, and decreased inotropic reserve. beta-blockers act to block excessive catecholamine stimulation of betaARs to decrease cellular apoptotic signaling and normalize beta1AR expression and inotropy. Whereas these actions reduce cardiac remodeling and mortality outcomes, the effects are not sustained. Converse to G-protein-dependent signaling, beta arrestin-dependent signaling promotes cardiomyocyte survival. Given that beta2AR expression is unaltered in CHF, a beta-arrestin-biased agonist that operates through the beta2AR represents a potentially useful therapeutic approach. Carvedilol, a currently prescribed nonselective beta-blocker, has been classified as a beta-arrestin-biased agonist that can inhibit basal signaling from betaARs and also stimulate cell survival signaling pathways. To understand the relative contribution of beta-arrestin bias to the efficacy of select beta-blockers, a specific beta-arrestin-biased pepducin for the beta2AR, intracellular loop (ICL)1 9, was used to decouple beta-arrestin-biased signaling from occupation of the orthosteric ligand-binding pocket. With similar efficacy to carvedilol, ICL1-9 was able to promote beta2AR phosphorylation, beta-arrestin recruitment, beta2AR internalization, and beta-arrestin-biased signaling. Interestingly, ICL1-9 was also able to induce beta2AR- and beta-arrestin-dependent and Ca(2+)-independent contractility in primary adult murine cardiomyocytes, whereas carvedilol had no efficacy. Thus, ICL1-9 is an effective tool to access a pharmacological profile stimulating cardioprotective signaling and inotropic effects through the beta2AR and serves as a model for the next generation of cardiovascular drug development. PMID- 27354519 TI - Correction to Supporting Information for Li et al., Root exudates drive interspecific facilitation by enhancing nodulation and N2 fixation. PMID- 27354518 TI - Tautomerization-dependent recognition and excision of oxidation damage in base excision DNA repair. AB - NEIL1 (Nei-like 1) is a DNA repair glycosylase guarding the mammalian genome against oxidized DNA bases. As the first enzymes in the base-excision repair pathway, glycosylases must recognize the cognate substrates and catalyze their excision. Here we present crystal structures of human NEIL1 bound to a range of duplex DNA. Together with computational and biochemical analyses, our results suggest that NEIL1 promotes tautomerization of thymine glycol (Tg)-a preferred substrate-for optimal binding in its active site. Moreover, this tautomerization event also facilitates NEIL1-catalyzed Tg excision. To our knowledge, the present example represents the first documented case of enzyme-promoted tautomerization for efficient substrate recognition and catalysis in an enzyme-catalyzed reaction. PMID- 27354520 TI - Chromosome-level assembly of Arabidopsis thaliana Ler reveals the extent of translocation and inversion polymorphisms. AB - Resequencing or reference-based assemblies reveal large parts of the small-scale sequence variation. However, they typically fail to separate such local variation into colinear and rearranged variation, because they usually do not recover the complement of large-scale rearrangements, including transpositions and inversions. Besides the availability of hundreds of genomes of diverse Arabidopsis thaliana accessions, there is so far only one full-length assembled genome: the reference sequence. We have assembled 117 Mb of the A. thaliana Landsberg erecta (Ler) genome into five chromosome-equivalent sequences using a combination of short Illumina reads, long PacBio reads, and linkage information. Whole-genome comparison against the reference sequence revealed 564 transpositions and 47 inversions comprising ~3.6 Mb, in addition to 4.1 Mb of nonreference sequence, mostly originating from duplications. Although rearranged regions are not different in local divergence from colinear regions, they are drastically depleted for meiotic recombination in heterozygotes. Using a 1.2-Mb inversion as an example, we show that such rearrangement-mediated reduction of meiotic recombination can lead to genetically isolated haplotypes in the worldwide population of A. thaliana Moreover, we found 105 single-copy genes, which were only present in the reference sequence or the Ler assembly, and 334 single-copy orthologs, which showed an additional copy in only one of the genomes. To our knowledge, this work gives first insights into the degree and type of variation, which will be revealed once complete assemblies will replace resequencing or other reference-dependent methods. PMID- 27354521 TI - Changes in genetic selection differentials and generation intervals in US Holstein dairy cattle as a result of genomic selection. AB - Seven years after the introduction of genomic selection in the United States, it is now possible to evaluate the impact of this technology on the population. Selection differential(s) (SD) and generation interval(s) (GI) were characterized in a four-path selection model that included sire(s) of bulls (SB), sire(s) of cows (SC), dam(s) of bulls (DB), and dam(s) of cows (DC). Changes in SD over time were estimated for milk, fat, and protein yield; somatic cell score (SCS); productive life (PL); and daughter pregnancy rate (DPR) for the Holstein breed. In the period following implementation of genomic selection, dramatic reductions were seen in GI, especially the SB and SC paths. The SB GI reduced from ~7 y to less than 2.5 y, and the DB GI fell from about 4 y to nearly 2.5 y. SD were relatively stable for yield traits, although modest gains were noted in recent years. The most dramatic response to genomic selection was observed for the lowly heritable traits DPR, PL, and SCS. Genetic trends changed from close to zero to large and favorable, resulting in rapid genetic improvement in fertility, lifespan, and health in a breed where these traits eroded over time. These results clearly demonstrate the positive impact of genomic selection in US dairy cattle, even though this technology has only been in use for a short time. Based on the four-path selection model, rates of genetic gain per year increased from ~50-100% for yield traits and from threefold to fourfold for lowly heritable traits. PMID- 27354522 TI - Temperature and atmospheric CO2 concentration estimates through the PETM using triple oxygen isotope analysis of mammalian bioapatite. AB - The Paleocene-Eocene Thermal Maximum (PETM) is a remarkable climatic and environmental event that occurred 56 Ma ago and has importance for understanding possible future climate change. The Paleocene-Eocene transition is marked by a rapid temperature rise contemporaneous with a large negative carbon isotope excursion (CIE). Both the temperature and the isotopic excursion are well documented by terrestrial and marine proxies. The CIE was the result of a massive release of carbon into the atmosphere. However, the carbon source and quantities of CO2 and CH4 greenhouse gases that contributed to global warming are poorly constrained and highly debated. Here we combine an established oxygen isotope paleothermometer with a newly developed triple oxygen isotope paleo-CO2 barometer. We attempt to quantify the source of greenhouse gases released during the Paleocene-Eocene transition by analyzing bioapatite of terrestrial mammals. Our results are consistent with previous estimates of PETM temperature change and suggest that not only CO2 but also massive release of seabed methane was the driver for CIE and PETM. PMID- 27354524 TI - Air pollutant emissions from Chinese households: A major and underappreciated ambient pollution source. AB - As part of the 12th Five-Year Plan, the Chinese government has developed air pollution prevention and control plans for key regions with a focus on the power, transport, and industrial sectors. Here, we investigate the contribution of residential emissions to regional air pollution in highly polluted eastern China during the heating season, and find that dramatic improvements in air quality would also result from reduction in residential emissions. We use the Weather Research and Forecasting model coupled with Chemistry to evaluate potential residential emission controls in Beijing and in the Beijing, Tianjin, and Hebei (BTH) region. In January and February 2010, relative to the base case, eliminating residential emissions in Beijing reduced daily average surface PM2.5 (particulate mater with aerodynamic diameter equal or smaller than 2.5 micrometer) concentrations by 14 +/- 7 MUg?m(-3) (22 +/- 6% of a baseline concentration of 67 +/- 41 MUg?m(-3); mean +/- SD). Eliminating residential emissions in the BTH region reduced concentrations by 28 +/- 19 MUg?m(-3) (40 +/- 9% of 67 +/- 41 MUg?m(-3)), 44 +/- 27 MUg?m(-3) (43 +/- 10% of 99 +/- 54 MUg?m( 3)), and 25 +/- 14 MUg?m(-3) (35 +/- 8% of 70 +/- 35 MUg?m(-3)) in Beijing, Tianjin, and Hebei provinces, respectively. Annually, elimination of residential sources in the BTH region reduced emissions of primary PM2.5 by 32%, compared with 5%, 6%, and 58% achieved by eliminating emissions from the transportation, power, and industry sectors, respectively. We also find air quality in Beijing would benefit substantially from reductions in residential emissions from regional controls in Tianjin and Hebei, indicating the value of policies at the regional level. PMID- 27354523 TI - Faster reproductive rates trade off against offspring growth in wild chimpanzees. AB - Life history theory predicts a trade-off between offspring quality and quantity. Among large-bodied mammals, prolonged lactation and infant dependence suggest particularly strong potential for a quality-quantity trade-off to exist. Humans are one of the only such species to have been examined, providing mixed evidence under a peculiar set of circumstances, including extensive nutritional provisioning by nonmothers and extrasomatic wealth transmission. Here, we examine trade-offs between reproductive rate and one aspect of offspring quality (body size) in wild chimpanzees (Pan troglodytes schweinfurthii), a species with long periods of infant dependence and little direct provisioning. Juvenile lean body mass, estimated using urinary creatinine excretion, was positively associated with the interval to the next sibling's birth. These effects persisted into adolescence and were not moderated by maternal identity. Maternal depletion could not explain poor offspring growth, as older mothers had larger offspring, and low maternal energy balance during lactation predicted larger, not smaller, juvenile size. Instead, our data suggest that offspring growth suffers when mothers wean early to invest in new reproductive efforts. These findings indicate that chimpanzee mothers with the resources to do so prioritize production of new offspring over prolonged investment in current offspring. PMID- 27354525 TI - Epigenetics and energetics in ventral hippocampus mediate rapid antidepressant action: Implications for treatment resistance. AB - Although regulation of energy metabolism has been linked with multiple disorders, its role in depression and responsiveness to antidepressants is less known. We found that an epigenetic and energetic agent, acetyl-l-carnitine (LAC, oral administration), rapidly rescued the depressive- and central and systemic metabolic-like phenotype of LAC-deficient Flinders Sensitive Line rats (FSL). After acute stress during LAC treatment, a subset of FSL continued to respond to LAC (rFSL), whereas the other subset did not (nrFSL). RNA sequencing of the ventral dentate gyrus, a mood-regulatory region, identified metabolic factors as key markers predisposing to depression (insulin receptors Insr, glucose transporters Glut-4 and Glut-12, and the regulator of appetite Cartpt) and to LAC responsiveness (leptin receptors Lepr, metabotropic glutamate receptors-2 mGlu2, neuropeptide-Y NPY, and mineralocorticoid receptors MR). Furthermore, we found that stress-induced treatment resistance in nrFSL shows a new gene profile, including the metabolic regulator factors elongation of long chain fatty acids 7 (Elovl7) and cytochrome B5 reductase 2 (Cyb5r2) and the synaptic regulator NPAS4. Finally, while improving central energy regulation and exerting rapid antidepressant-like effects, LAC corrected a systemic hyperinsulinemia and hyperglicemia in rFSL and failed to do that in nrFSL. These findings establish CNS energy regulation as a factor to be considered for the development of better therapeutics. Agents such as LAC that regulate metabolic factors and reduce glutamate overflow could rapidly ameliorate depression and could also be considered for treatment of insulin resistance in depressed subjects. The approach here serves as a model for identifying markers and underlying mechanisms of predisposition to diseases and treatment responsiveness that may be useful in translation to human behavior and psychopathology. PMID- 27354527 TI - Salinity of deep groundwater in California: Water quantity, quality, and protection. AB - Deep groundwater aquifers are poorly characterized but could yield important sources of water in California and elsewhere. Deep aquifers have been developed for oil and gas extraction, and this activity has created both valuable data and risks to groundwater quality. Assessing groundwater quantity and quality requires baseline data and a monitoring framework for evaluating impacts. We analyze 938 chemical, geological, and depth data points from 360 oil/gas fields across eight counties in California and depth data from 34,392 oil and gas wells. By expanding previous groundwater volume estimates from depths of 305 m to 3,000 m in California's Central Valley, an important agricultural region with growing groundwater demands, fresh [<3,000 ppm total dissolved solids (TDS)] groundwater volume is almost tripled to 2,700 km(3), most of it found shallower than 1,000 m. The 3,000-m depth zone also provides 3,900 km(3) of fresh and saline water, not previously estimated, that can be categorized as underground sources of drinking water (USDWs; <10,000 ppm TDS). Up to 19% and 35% of oil/gas activities have occurred directly in freshwater zones and USDWs, respectively, in the eight counties. Deeper activities, such as wastewater injection, may also pose a potential threat to groundwater, especially USDWs. Our findings indicate that California's Central Valley alone has close to three times the volume of fresh groundwater and four times the volume of USDWs than previous estimates suggest. Therefore, efforts to monitor and protect deeper, saline groundwater resources are needed in California and beyond. PMID- 27354526 TI - A face-selective ventral occipito-temporal map of the human brain with intracerebral potentials. AB - Human neuroimaging studies have identified a network of distinct face-selective regions in the ventral occipito-temporal cortex (VOTC), with a right hemispheric dominance. To date, there is no evidence for this hemispheric and regional specialization with direct measures of brain activity. To address this gap in knowledge, we recorded local neurophysiological activity from 1,678 contact electrodes implanted in the VOTC of a large group of epileptic patients (n = 28). They were presented with natural images of objects at a rapid fixed rate (six images per second: 6 Hz), with faces interleaved as every fifth stimulus (i.e., 1.2 Hz). High signal-to-noise ratio face-selective responses were objectively (i.e., exactly at the face stimulation frequency) identified and quantified throughout the whole VOTC. Face-selective responses were widely distributed across the whole VOTC, but also spatially clustered in specific regions. Among these regions, the lateral section of the right middle fusiform gyrus showed the largest face-selective response by far, offering, to our knowledge, the first supporting evidence of two decades of neuroimaging observations with direct neural measures. In addition, three distinct regions with a high proportion of face-selective responses were disclosed in the right ventral anterior temporal lobe, a region that is undersampled in neuroimaging because of magnetic susceptibility artifacts. A high proportion of contacts responding only to faces (i.e., "face-exclusive" responses) were found in these regions, suggesting that they contain populations of neurons involved in dedicated face-processing functions. Overall, these observations provide a comprehensive mapping of visual category selectivity in the whole human VOTC with direct neural measures. PMID- 27354528 TI - Highly sensitive and unbiased approach for elucidating antibody repertoires. AB - Developing B lymphocytes undergo V(D)J recombination to assemble germ-line V, D, and J gene segments into exons that encode the antigen-binding variable region of Ig heavy (H) and light (L) chains. IgH and IgL chains associate to form the B cell receptor (BCR), which, upon antigen binding, activates B cells to secrete BCR as an antibody. Each of the huge number of clonally independent B cells expresses a unique set of IgH and IgL variable regions. The ability of V(D)J recombination to generate vast primary B-cell repertoires results from a combinatorial assortment of large numbers of different V, D, and J segments, coupled with diversification of the junctions between them to generate the complementary determining region 3 (CDR3) for antigen contact. Approaches to evaluate in depth the content of primary antibody repertoires and, ultimately, to study how they are further molded by secondary mutation and affinity maturation processes are of great importance to the B-cell development, vaccine, and antibody fields. We now describe an unbiased, sensitive, and readily accessible assay, referred to as high-throughput genome-wide translocation sequencing adapted repertoire sequencing (HTGTS-Rep-seq), to quantify antibody repertoires. HTGTS-Rep-seq quantitatively identifies the vast majority of IgH and IgL V(D)J exons, including their unique CDR3 sequences, from progenitor and mature mouse B lineage cells via the use of specific J primers. HTGTS-Rep-seq also accurately quantifies DJH intermediates and V(D)J exons in either productive or nonproductive configurations. HTGTS-Rep-seq should be useful for studies of human samples, including clonal B-cell expansions, and also for following antibody affinity maturation processes. PMID- 27354529 TI - Nanofluid of graphene-based amphiphilic Janus nanosheets for tertiary or enhanced oil recovery: High performance at low concentration. AB - The current simple nanofluid flooding method for tertiary or enhanced oil recovery is inefficient, especially when used with low nanoparticle concentration. We have designed and produced a nanofluid of graphene-based amphiphilic nanosheets that is very effective at low concentration. Our nanosheets spontaneously approached the oil-water interface and reduced the interfacial tension in a saline environment (4 wt % NaCl and 1 wt % CaCl2), regardless of the solid surface wettability. A climbing film appeared and grew at moderate hydrodynamic condition to encapsulate the oil phase. With strong hydrodynamic power input, a solid-like interfacial film formed and was able to return to its original form even after being seriously disturbed. The film rapidly separated oil and water phases for slug-like oil displacement. The unique behavior of our nanosheet nanofluid tripled the best performance of conventional nanofluid flooding methods under similar conditions. PMID- 27354530 TI - Bacterial lipids activate, synergize, and inhibit a developmental switch in choanoflagellates. AB - In choanoflagellates, the closest living relatives of animals, multicellular rosette development is regulated by environmental bacteria. The simplicity of this evolutionarily relevant interaction provides an opportunity to identify the molecules and regulatory logic underpinning bacterial regulation of development. We find that the rosette-inducing bacterium Algoriphagus machipongonensis produces three structurally divergent classes of bioactive lipids that, together, activate, enhance, and inhibit rosette development in the choanoflagellate Salpingoeca rosetta. One class of molecules, the lysophosphatidylethanolamines (LPEs), elicits no response on its own but synergizes with activating sulfonolipid rosette-inducing factors (RIFs) to recapitulate the full bioactivity of live Algoriphagus. LPEs, although ubiquitous in bacteria and eukaryotes, have not previously been implicated in the regulation of a host-microbe interaction. This study reveals that multiple bacterially produced lipids converge to activate, enhance, and inhibit multicellular development in a choanoflagellate. PMID- 27354531 TI - Substrate-assisted mechanism of RNP disruption by the spliceosomal Brr2 RNA helicase. AB - The Brr2 RNA helicase disrupts the U4/U6 di-small nuclear RNA-protein complex (di snRNP) during spliceosome activation via ATP-driven translocation on the U4 snRNA strand. However, it is unclear how bound proteins influence U4/U6 unwinding, which regions of the U4/U6 duplex the helicase actively unwinds, and whether U4/U6 components are released as individual molecules or as subcomplexes. Here, we set up a recombinant Brr2-mediated U4/U6 di-snRNP disruption system, showing that sequential addition of the U4/U6 proteins small nuclear ribonucleoprotein associated protein 1 (Snu13), pre-mRNA processing factor 31 (Prp31), and Prp3 to U4/U6 di-snRNA leads to a stepwise decrease of Brr2-mediated U4/U6 unwinding, but that unwinding is largely restored by a Brr2 cofactor, the C-terminal Jab1/MPN domain of the Prp8 protein. Brr2-mediated U4/U6 unwinding was strongly inhibited by mutations in U4/U6 di-snRNAs that diminish the ability of U6 snRNA to adopt an alternative conformation but leave the number and kind of U4/U6 base pairs unchanged. Irrespective of the presence of the cofactor, the helicase segregated a Prp3-Prp31-Snu13-U4/U6 RNP into an intact Prp31-Snu13-U4 snRNA particle, free Prp3, and free U6 snRNA. Together, these observations suggest that Brr2 translocates only a limited distance on the U4 snRNA strand and does not actively release RNA-bound proteins. Unwinding is then completed by the partially displaced U6 snRNA adopting an alternative conformation, which leads to dismantling of the Prp3-binding site on U4/U6 di-snRNA but leaves the Prp31- and Snu13-binding sites on U4 snRNA unaffected. In this fashion, Brr2 can activate the spliceosome by stripping U6 snRNA of all precatalytic binding partners, while minimizing logistic requirements for U4/U6 di-snRNP reassembly after splicing. PMID- 27354532 TI - Biomechanics of red blood cells in human spleen and consequences for physiology and disease. AB - Red blood cells (RBCs) can be cleared from circulation when alterations in their size, shape, and deformability are detected. This function is modulated by the spleen-specific structure of the interendothelial slit (IES). Here, we present a unique physiological framework for development of prognostic markers in RBC diseases by quantifying biophysical limits for RBCs to pass through the IES, using computational simulations based on dissipative particle dynamics. The results show that the spleen selects RBCs for continued circulation based on their geometry, consistent with prior in vivo observations. A companion analysis provides critical bounds relating surface area and volume for healthy RBCs beyond which the RBCs fail the "physical fitness test" to pass through the IES, supporting independent experiments. Our results suggest that the spleen plays an important role in determining distributions of size and shape of healthy RBCs. Because mechanical retention of infected RBC impacts malaria pathogenesis, we studied key biophysical parameters for RBCs infected with Plasmodium falciparum as they cross the IES. In agreement with experimental results, surface area loss of an infected RBC is found to be a more important determinant of splenic retention than its membrane stiffness. The simulations provide insights into the effects of pressure gradient across the IES on RBC retention. By providing quantitative biophysical limits for RBCs to pass through the IES, the narrowest circulatory bottleneck in the spleen, our results offer a broad approach for developing quantitative markers for diseases such as hereditary spherocytosis, thalassemia, and malaria. PMID- 27354533 TI - Enzyme surface rigidity tunes the temperature dependence of catalytic rates. AB - The structural origin of enzyme adaptation to low temperature, allowing efficient catalysis of chemical reactions even near the freezing point of water, remains a fundamental puzzle in biocatalysis. A remarkable universal fingerprint shared by all cold-active enzymes is a reduction of the activation enthalpy accompanied by a more negative entropy, which alleviates the exponential decrease in chemical reaction rates caused by lowering of the temperature. Herein, we explore the role of protein surface mobility in determining this enthalpy-entropy balance. The effects of modifying surface rigidity in cold- and warm-active trypsins are demonstrated here by calculation of high-precision Arrhenius plots and thermodynamic activation parameters for the peptide hydrolysis reaction, using extensive computer simulations. The protein surface flexibility is systematically varied by applying positional restraints, causing the remarkable effect of turning the cold-active trypsin into a variant with mesophilic characteristics without changing the amino acid sequence. Furthermore, we show that just restraining a key surface loop causes the same effect as a point mutation in that loop between the cold- and warm-active trypsin. Importantly, changes in the activation enthalpy-entropy balance of up to 10 kcal/mol are almost perfectly balanced at room temperature, whereas they yield significantly higher rates at low temperatures for the cold-adapted enzyme. PMID- 27354534 TI - Large-scale climatic and geophysical controls on the leaf economics spectrum. AB - Leaf economics spectrum (LES) theory suggests a universal trade-off between resource acquisition and storage strategies in plants, expressed in relationships between foliar nitrogen (N) and phosphorus (P), leaf mass per area (LMA), and photosynthesis. However, how environmental conditions mediate LES trait interrelationships, particularly at large biospheric scales, remains unknown because of a lack of spatially explicit data, which ultimately limits our understanding of ecosystem processes, such as primary productivity and biogeochemical cycles. We used airborne imaging spectroscopy and geospatial modeling to generate, to our knowledge, the first biospheric maps of LES traits, here centered on 76 million ha of Andean and Amazonian forest, to assess climatic and geophysical determinants of LES traits and their interrelationships. Elevation and substrate were codominant drivers of leaf trait distributions. Multiple additional climatic and geophysical factors were secondary determinants of plant traits. Anticorrelations between N and LMA followed general LES theory, but topo-edaphic conditions strongly mediated and, at times, eliminated this classic relationship. We found no evidence for simple P-LMA or N-P trade-offs in forest canopies; rather, we mapped a continuum of N-P-LMA interactions that are sensitive to elevation and temperature. Our results reveal nested climatic and geophysical filtering of LES traits and their interrelationships, with important implications for predictions of forest productivity and acclimation to rapid climate change. PMID- 27354535 TI - Binocular rivalry from invisible patterns. AB - Binocular rivalry arises when incompatible images are presented to the two eyes. If the two eyes' conflicting features are invisible, leading to identical perceptual interpretations, does rivalry competition still occur? Here we investigated whether binocular rivalry can be induced from conflicting but invisible spatial patterns. A chromatic grating counterphase flickering at 30 Hz appeared uniform, but produced significant tilt aftereffect and orientation selective adaptation. The invisible pattern also generated significant BOLD activities in the early visual cortex, with minimal response in the parietal and frontal cortical areas. Compared with perceptually matched uniform stimuli, a monocularly presented invisible chromatic grating enhanced the rivalry competition with a low-contrast visible grating presented to the other eye. Furthermore, switching from a uniform field to a perceptually matched invisible chromatic grating produced interocular suppression at approximately 200 ms after onset of the invisible grating. Experiments using briefly presented monocular probes revealed evidence for sustained rivalry competition between two invisible gratings during continuous dichoptic presentations. These findings indicate that even without visible interocular conflict, and with minimal engagement of frontoparietal cortex and consciousness related top-down feedback, perceptually identical patterns with invisible conflict features produce rivalry competition in the early visual cortex. PMID- 27354536 TI - Critical review of bariatric surgery, medically supervised diets, and behavioural interventions for weight management in adults. AB - AIMS: Patient selection of weight management treatment option is often guided by a variety of factors. Currently, there is no comprehensive tool to facilitate informed decision-making for patients and clinicians. This article aims to synthesise evidence on the treatment effectiveness, health benefits, risks, and patient experiences of treatment options presently available at the Weight Management Clinic at The Ottawa Hospital (TOH), as a first step towards developing a decision aid. METHODS: Narrative and systematic reviews published in English between 1999 and 2014 were included that focused on one or more of the following weight management treatments in adults aged 18 years and over: roux-en y gastric bypass (RYGB), sleeve gastrectomy (SG), medically supervised meal replacement, and behavioural or lifestyle intervention. RESULTS: Overall, bariatric surgeries have received the greatest research attention and have been associated not only with greater weight loss and health benefit but also with greater risks, complications, and financial cost. Dietary programmes demonstrated weight loss and health benefits to a lesser extent than with surgery but were associated with lower and shorter-term risks and complications. Behavioural and lifestyle interventions have been studied less yet have shown significant, albeit small, weight loss outcomes alone and in combination with dietary or surgical options; they also appear to be the lowest risk interventions. Patient experiences of weight management options are mixed and not well understood. CONCLUSION: Further research is needed; however, this review identified some general trends related to weight loss outcomes, benefits, risks, and barriers for weight management options that have implications for shared treatment decision making. PMID- 27354537 TI - Intracellular mechanisms modulating gamma band activity in the pedunculopontine nucleus (PPN). AB - The pedunculopontine nucleus is a part of the reticular activating system, and is active during waking and REM sleep. Previous results showed that all PPN cells tested fired maximally at gamma frequencies when depolarized. This intrinsic membrane property was shown to be mediated by high-threshold N- and P/Q-type Ca(2+) channels. Recent studies show that the PPN contains three independent populations of neurons which can generate gamma band oscillations through only N type channels, only P/Q-type channels, or both N- and P/Q-type channels. This study investigated the intracellular mechanisms modulating gamma band activity in each population of neurons. We performed in vitro patch-clamp recordings of PPN neurons from Sprague-Dawley rat pups, and applied 1-sec ramps to induce intrinsic membrane oscillations. Our results show that there are two pathways modulating gamma band activity in PPN neurons. We describe populations of neurons mediating gamma band activity through only N-type channels and the cAMP/PKA pathway (presumed "REM-on" neurons), through only P/Q-type channels and the CaMKII pathway (presumed "Wake-on" neurons), and a third population which can mediate gamma activity through both N-type channels and cAMP/PK and P/Q-type channels and CaMKII (presumed "Wake/REM-on" neurons). These novel results suggest that PPN gamma oscillations are modulated by two independent pathways related to different Ca(2+) channel types. PMID- 27354538 TI - Sex differences in the response to resistance exercise training in older people. AB - Resistance exercise training is known to be effective in increasing muscle mass in older people. Acute measurement of protein metabolism data has indicated that the magnitude of response may differ between sexes. We compared adaptive responses in muscle mass and function to 18 weeks resistance exercise training in a cohort of older (>65 years) men and women. Resistance exercise training improved knee extensor maximal torque, 4 m walk time, time to complete five chair rises, muscle anatomical cross-sectional area (ACSA) and muscle quality with no effect on muscle fat/water ratio or plasma glucose, insulin, triacylglycerol, IL 6, and TNF-alpha Differences between sexes were observed for knee extensor maximal torque and muscle quality with greater increases observed in men versus women (P < 0.05). Maximal torque increased by 15.8 +/- 10.6% in women and 41.7 +/ 25.5% in men, whereas muscle quality increased by 8.8 +/- 17.5% in women and by 33.7 +/- 25.6% in men. In conclusion, this study has demonstrated a difference in the magnitude of adaptation, of some of the outcome measures employed, in response to 18 weeks of resistance exercise training between men and women. The mechanisms underlying this observation remain to be established. PMID- 27354539 TI - Measuring the short-term substrate utilization response to high-carbohydrate and high-fat meals in the whole-body indirect calorimeter. AB - The paper demonstrates that minute-to-minute metabolic response to meals with different macronutrient content can be measured and discerned in the whole-body indirect calorimeter. The ability to discriminate between high-carbohydrate and high-fat meals is achieved by applying a modified regularization technique with additional constraints imposed on oxygen consumption rate. These additional constraints reduce the differences in accuracy between the oxygen and carbon dioxide analyzers. The modified technique was applied to 63 calorimeter sessions that were each 24 h long. The data were collected from 16 healthy volunteers (eight males, eight females, aged 22-35 years). Each volunteer performed four 24 h long calorimeter sessions. At each session, they received one of four treatment combinations involving exercise (high or low intensity) and diet (a high-fat or high-carbohydrate shake for lunch). One volunteer did not complete all four assignments, which brought the total number of sessions to 63 instead of 64. During the 24-h stay in the calorimeter, subjects wore a continuous glucose monitoring system, which was used as a benchmark for subject's postprandial glycemic response. The minute-by-minute respiratory exchange ratio (RER) data showed excellent agreement with concurrent subcutaneous glucose concentrations in postprandial state. The averaged minute-to-minute RER response to the high carbohydrate shake was significantly different from the response to high-fat shake. Also, postprandial RER slopes were significantly different for two dietary treatments. The results show that whole-body respiration calorimeters can be utilized as tools to study short-term kinetics of substrate oxidation in humans. PMID- 27354540 TI - Heterozygous Hfe gene deletion leads to impaired glucose homeostasis, but not liver injury in mice fed a high-calorie diet. AB - Heterozygous mutations of the Hfe gene have been proposed as cofactors in the development and progression of nonalcoholic fatty liver disease (NAFLD). Homozygous Hfe deletion previously has been shown to lead to dysregulated hepatic lipid metabolism and accentuated liver injury in a dietary mouse model of NAFLD We sought to establish whether heterozygous deletion of Hfe is sufficient to promote liver injury when mice are exposed to a high-calorie diet (HCD). Eight week-old wild-type and Hfe(+/-) mice received 8 weeks of a control diet or HCD Liver histology and pathways of lipid and iron metabolism were analyzed. Liver histology demonstrated that mice fed a HCD had increased NAFLD activity score (NAS), steatosis, and hepatocyte ballooning. However, liver injury was unaffected by Hfe genotype. Hepatic iron concentration (HIC) was increased in Hfe(+/-) mice of both dietary groups. HCD resulted in a hepcidin-independent reduction in HIC Hfe(+/-) mice demonstrated raised fasting serum glucose concentrations and HOMA IR score, despite unaltered serum adiponectin concentrations. Downstream regulators of hepatic de novo lipogenesis (pAKT, SREBP-1, Fas, Scd1) and fatty acid oxidation (AdipoR2, Pparalpha, Cpt1) were largely unaffected by genotype. In summary, heterozygous Hfe gene deletion is associated with impaired iron and glucose metabolism. However, unlike homozygous Hfe deletion, heterozygous gene deletion did not affect lipid metabolism pathways or liver injury in this model. PMID- 27354541 TI - Sexually dimorphic adaptation of cardiac function: roles of epoxyeicosatrienoic acid and peroxisome proliferator-activated receptors. AB - Epoxyeicosatrienoic acids (EETs) are cardioprotective mediators metabolized by soluble epoxide hydrolase (sEH) to form corresponding diols (DHETs). As a sex susceptible target, sEH is involved in the sexually dimorphic regulation of cardiovascular function. Thus, we hypothesized that the female sex favors EET mediated potentiation of cardiac function via downregulation of sEH expression, followed by upregulation of peroxisome proliferator-activated receptors (PPARs). Hearts were isolated from male (M) and female (F) wild-type (WT) and sEH-KO mice, and perfused with constant flow at different preloads. Basal coronary flow required to maintain the perfusion pressure at 100 mmHg was significantly greater in females than males, and sEH-KO than WT mice. All hearts displayed a dose dependent decrease in coronary resistance and increase in cardiac contractility, represented as developed tension in response to increases in preload. These responses were also significantly greater in females than males, and sEH-KO than WT 14,15-EEZE abolished the sex-induced (F vs. M) and transgenic model-dependent (KO vs. WT) differences in the cardiac contractility, confirming an EET-driven response. Compared with M-WT controls, F-WT hearts expressed downregulation of sEH, associated with increased EETs and reduced DHETs, a pattern comparable to that observed in sEH-KO hearts. Coincidentally, F-WT and sEH-KO hearts exhibited increased PPARalpha expression, but comparable expression of eNOS, PPARbeta, and EET synthases. In conclusion, female-specific downregulation of sEH initiates an EET-dependent adaptation of cardiac function, characterized by increased coronary flow via reduction in vascular resistance, and promotion of cardiac contractility, a response that could be further intensified by PPARalpha. PMID- 27354542 TI - Sleep restriction acutely impairs glucose tolerance in rats. AB - Chronic sleep curtailment in humans has been related to impairment of glucose metabolism. To better understand the underlying mechanisms, the purpose of the present study was to investigate the effect of acute sleep deprivation on glucose tolerance in rats. A group of rats was challenged by 4-h sleep deprivation in the early rest period, leading to prolonged (16 h) wakefulness. Another group of rats was allowed to sleep during the first 4 h of the light period and sleep deprived in the next 4 h. During treatment, food was withdrawn to avoid a postmeal rise in plasma glucose. An intravenous glucose tolerance test (IVGTT) was performed immediately after the sleep deprivation period. Sleep deprivation at both times of the day similarly impaired glucose tolerance and reduced the early-phase insulin responses to a glucose challenge. Basal concentrations of plasma glucose, insulin, and corticosterone remained unchanged after sleep deprivation. Throughout IVGTTs, plasma corticosterone concentrations were not different between the control and sleep-deprived group. Together, these results demonstrate that independent of time of day and sleep pressure, short sleep deprivation during the resting phase favors glucose intolerance in rats by attenuating the first-phase insulin response to a glucose load. In conclusion, this study highlights the acute adverse effects of only a short sleep restriction on glucose homeostasis. PMID- 27354543 TI - Hypoxia and hyperoxia potentiate PAF receptor-mediated effects in newborn ovine pulmonary arterial smooth muscle cells: significance in oxygen therapy of PPHN. AB - Platelet-activating factor (PAF) acting via its receptor (PAFR) is implicated in the pathogenesis of persistent pulmonary hypertension of the newborn (PPHN). Effects of long-term oxygen therapy on newborn lung are not well understood; therefore, we studied the effect of oxygen tension on ovine newborn pulmonary artery smooth muscle cells (NBPASMC). Our global hypothesis is that PPHN results from failure of newborn lamb pulmonary system to downregulate PAFR activity or to upregulate vasodilatory cyclic nucleotides (Cnucs) activity. NBPASMC from newborns 6-12 days old were studied in vitro at three different oxygen tensions (pO2, [Torr]: hypoxia, <40; normoxia, 80-100; and hyperoxia, >100 Torr often clinically imposed upon newborns with PPHN) PAFR- and Cnucs mediated effects were determined. PAFR and PKA Calpha mRNA expression as well as prostacyclin, thromboxane, cAMP production, and DNA synthesis was studied to assess PAFR mediated hypertrophy and/or hyperplasia. Hypoxia and hyperoxia increased specific PAFR binding. PAF treatment during hyperoxia increased PAFR gene, but decreased PKA-Calpha gene expression. Hypoxia and hyperoxia increased NBPASMC proliferation via PAFR signaling. Baseline prostacyclin level was ninefold greater than in fetal PASMC, whereas baseline thromboxane was sevenfold less suggesting greater postnatal cyclooxygenase activity in NBPASMC PAF decreased, while forskolin and 8 Br-cAMP increased cAMP production. Decrease of PAFR effects by Cnucs indicates that normal newborn PA physiology favors vasodilator pathways to minimize PAF induced hypertrophy or hyperplasia. We speculate that failure of newborn lung to anchor downregulation of vasoconstrictors with upregulation of vasodilators leads to PPHN. PMID- 27354544 TI - Pericardial patch venoplasty heals via attraction of venous progenitor cells. AB - Pericardial patches are commonly used during cardiovascular surgery to close blood vessels. In arteries, patches accumulate arterial progenitor cells; we hypothesized that venous patches would accumulate venous progenitor cells, in the absence of arterial pressure. We developed a novel rat inferior vena cava (IVC) venotomy model and repaired it with a pericardial patch. Cells infiltrated the patch to form a thick neointima by day 7; some cells were CD34(+)/VEGFR2(+) and CD31(+)/Eph-B4(+) consistent with development of venous identity in the healing patch. Compared to arterial patches, the venous patches had increased neointimal thickness at day 7 without any pseudoaneurysms. Addition of an arteriovenous fistula (AVF) to increase blood flow on the patch resulted in reduced patch neointimal thickness and proliferation, but neointimal thickness was not reversible with AVF ligation. These results show that rat patch venoplasty is a novel model of aggressive venous neointimal hyperplasia. PMID- 27354545 TI - Gallbladder motility and the sex of the guinea pig. AB - Progesterone (P), 17beta-estradiol (E2), and dihydrotestosterone (DHT) affect gallbladder motility. When gallbladders were taken from women and men, women had more estrogen and P receptors than men. Both P and E2 had an inhibitory effect upon gallbladder contractility in men and premenopausal and postmenopausal women. Similar findings have been reported in gallbladder strips from male and female guinea pigs. In the present study, there was no significant difference in the amount of E2-, P-, or DHT-induced relaxation of CCK-induced tension when the responses in gallbladder strips from male and female guinea pigs were compared. Three metabolites of P were used: 17-hydroxyprogesterone (17-P), 20alpha hydroxyprogesterone (20-P), and 21-hydroxyprogesterone (21-P). There was no significant difference in the responses from strips from male and female guinea pigs. In order to determine if the effects of E2 and P were additive, strips from male animals were exposed to either E2 or P and the amount of relaxation recorded. After recovery, the strips were exposed to E2 or P in reverse order to ensure the order of treatment had no effect. Then, the strips were treated with both E2 and P simultaneously and the relaxation recorded. This procedure was repeated with strips from female guinea pigs. The effect of E2 and P was found to be additive; however, the response of the strips from each sex were not significantly different. It is concluded that the sex of the guinea pig has no significant effect on the response to the sex hormones used. PMID- 27354547 TI - A pictorial review of imaging in paediatric stroke. AB - Stroke is recognised as an important disease in adults. Paediatric stroke is less understood, yet still an important cause of morbidity and mortality, with an incidence of 5 per 100 000 children and is one of the top 10 leading causes of death in children. In adults the vast majority of strokes are ischaemic, whereas in children haemorrhage makes up half the cases. The incidence of neonatal stroke is much higher, at up to 45 per 100 000 population; however, the underlying causes are less understood. This paper acts as a guide to the different causes of stroke with the key differences on imaging discussed. PMID- 27354546 TI - Micro-adhesion rings surrounding TCR microclusters are essential for T cell activation. AB - The immunological synapse (IS) formed at the interface between T cells and antigen-presenting cells represents a hallmark of initiation of acquired immunity. T cell activation is initiated at T cell receptor (TCR) microclusters (MCs), in which TCRs and signaling molecules assemble at the interface before IS formation. We found that each TCR-MC was transiently bordered by a ring structure made of integrin and focal adhesion molecules in the early phase of activation, which is similar in structure to the IS in microscale. The micro-adhesion ring is composed of LFA-1, focal adhesion molecules paxillin and Pyk2, and myosin II (MyoII) and is supported by F-actin core and MyoII activity through LFA-1 outside in signals. The formation of the micro-adhesion ring was transient but especially sustained upon weak TCR stimulation to recruit linker for activation of T cells (LAT) and SLP76. Perturbation of the micro-adhesion ring induced impairment of TCR-MC development and resulted in impaired cellular signaling and cell functions. Thus, the synapse-like structure composed of the core TCR-MC and surrounding micro-adhesion ring is a critical structure for initial T cell activation through integrin outside-in signals. PMID- 27354548 TI - Images: perineal pain and malodorous drainage in a patient with rectal cancer. PMID- 27354549 TI - Discovery of an expanded set of avian leukosis subroup E proviruses in chickens using Vermillion, a novel sequence capture and analysis pipeline. AB - Transposable elements (TEs), such as endogenous retroviruses (ERVs), are common in the genomes of vertebrates. ERVs result from retroviral infections of germ line cells, and once integrated into host DNA they become part of the host's heritable genetic material. ERVs have been ascribed positive effects on host physiology such as the generation of novel, adaptive genetic variation and resistance to infection, as well as negative effects as agents of tumorigenesis and disease. The avian leukosis virus subgroup E family (ALVE) of endogenous viruses of chickens has been used as a model system for studying the effects of ERVs on host physiology, and approximately 30 distinct ALVE proviruses have been described in the Gallus gallus genome. In this report we describe the development of a software tool, which we call Vermillion, and the use of this tool in combination with targeted next-generation sequencing (NGS) to increase the number of known proviruses belonging to the ALVE family of ERVs in the chicken genome by 4-fold, including expanding the number of known ALVE elements on chromosome 1 (Gga1) from the current 9 to a total of 40. Although we focused on the discovery of ALVE elements in chickens, with appropriate selection of target sequences Vermillion can be used to develop profiles of other families of ERVs and TEs in chickens as well as in species other than the chicken. PMID- 27354550 TI - Validation of Reverse-Engineered and Additive-Manufactured Microsurgical Instrument Prototype. AB - With advancements in imaging techniques, neurosurgical procedures are becoming highly precise and minimally invasive, thus demanding development of new ergonomically aesthetic instruments. Conventionally, neurosurgical instruments are manufactured using subtractive manufacturing methods. Such a process is complex, time-consuming, and impractical for prototype development and validation of new designs. Therefore, an alternative design process has been used utilizing blue light scanning, computer-aided designing, and additive manufacturing direct metal laser sintering (DMLS) for microsurgical instrument prototype development. Deviations of DMLS-fabricated instrument were studied by superimposing scan data of fabricated instrument with the computer-aided designing model. Content and concurrent validity of the fabricated prototypes was done by a group of 15 neurosurgeons by performing sciatic nerve anastomosis in small laboratory animals. Comparative scoring was obtained for the control and study instrument. T test was applied to the individual parameters and P values for force (P < .0001) and surface roughness (P < .01) were found to be statistically significant. These 2 parameters were further analyzed using objective measures. Results depicts that additive manufacturing by DMLS provides an effective method for prototype development. However, direct application of these additive-manufactured instruments in the operating room requires further validation. PMID- 27354551 TI - Evaluation of the Antimicrobial Efficacy of a Novel Rifampin/Minocycline-Coated, Noncrosslinked Porcine Acellular Dermal Matrix Compared With Uncoated Scaffolds for Soft Tissue Repair. AB - Background Despite meticulous aseptic technique and systemic antibiotics, bacterial colonization of mesh remains a critical issue in hernia repair. A novel minocycline/rifampin tyrosine-coated, noncrosslinked porcine acellular dermal matrix (XenMatrix AB) was developed to protect the device from microbial colonization for up to 7 days. The objective of this study was to evaluate the in vitro and in vivo antimicrobial efficacy of this device against clinically isolated methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli. Methods XenMatrix AB was compared with 5 existing uncoated soft tissue repair devices using in vitro methods of zone of inhibition (ZOI) and scanning electron microscopy (SEM) at 24 hours following inoculation with MRSA or E coli These devices were also evaluated at 7 days following dorsal implantation and inoculation with MRSA or E coli (60 male New Zealand white rabbits, n = 10 per group) for viable colony-forming units (CFU), abscess formation and histopathologic response, respectively. Results In vitro studies demonstrated a median ZOI of 36 mm for MRSA and 16 mm for E coli for XenMatrix AB, while all uncoated devices showed no inhibition of bacterial growth (0 mm). SEM also demonstrated no visual evidence of MRSA or E coli colonization on the surface of XenMatrix AB compared with colonization of all other uncoated devices. In vivo XenMatrix AB demonstrated complete inhibition of bacterial colonization, no abscess formation, and a reduced inflammatory response compared with uncoated devices. Conclusion We demonstrated that XenMatrix AB possesses potent in vitro and in vivo antimicrobial efficacy against clinically isolated MRSA and E coli compared with uncoated devices. PMID- 27354552 TI - Patient-Reported Convalescence and Quality of Life Recovery: A Comparison of Open and Robotic-Assisted Radical Cystectomy. AB - Background Robotic-assisted radical cystectomy (RARC) is gaining traction as a surgical approach, but there are limited data on patient-reported outcomes for this technique compared to open radical cystectomy (ORC). Objective To compare health-related quality of life (HRQoL) and short-term convalescence among bladder cancer patients who underwent ORC and RARC. Methods Review of a single institution bladder cancer database was conducted. Baseline and postoperative HRQoL was evaluated using the Bladder Cancer Index (BCI) for 324 patients who had ORC (n = 267) or RARC (n = 57) between 2008 and 2012. The BCI assesses function and bother in urinary, bowel, and sexual domains. Among 87 distinct patients (ORC n = 67, RARC n = 20), we also evaluated short-term postoperative convalescence using the Convalescence and Recovery Evaluation (CARE) questionnaire. Our primary outcomes were HRQoL within 12 months and short-term convalescence within 6 weeks following cystectomy. We fit generalized estimating equation regression models to estimate longitudinal changes in BCI scores within domains, and CARE domain score differences were tested with Wilcoxon rank-sum tests. Results Clinical characteristics and baseline BCI/CARE scores were similar between the 2 groups (all P > .05). Within 1 year after surgery, recovery of HRQoL across all BCI domains was comparable, with scores nearly returning to baseline at 1 year for all patients. CARE scores at 4 weeks revealed that patients treated with ORC had better pain (29.1 vs 20.0, P = .02) domain scores compared to RARC. These differences abated by week 6. Conclusions HRQoL recovery and short-term convalescence were similar in this cohort following ORC and RARC. PMID- 27354553 TI - Global Regulation of Plant Immunity by Histone Lysine Methyl Transferases. AB - Posttranslational modification of histones modulates gene expression affecting diverse biological functions. We showed that the Arabidopsis thaliana histone methyl transferases SET DOMAIN GROUP8 (SDG8) and SDG25 regulate pep1-, flg22-, and effector-triggered immunity as well as systemic acquired resistance. Genome wide basal and induced transcriptome changes regulated by SDG8 and/or SDG25 showed that two genes of the SDG-dependent transcriptome, CAROTENOID ISOMERASE2 (CCR2) and ECERIFERUM3 (CER3), were also required for plant immunity, establishing mechanisms in defense functions for SDG8 and SDG25. CCR2 catalyzes the biosynthesis of carotenoids, whereas CER3 is involved in the biosynthesis of cuticular wax. SDG8 and SDG25 affected distinct and overlapping global and locus specific histone H3 lysine 4 (H3K4) and histone H3 lysine 36 (H3K36) methylations. Loss of immunity in sdg mutants was attributed to altered global and CCR2- and CER3-specific histone lysine methylation (HLM). Loss of immunity in sdg, ccr2, and cer3 mutants was also associated with diminished accumulation of lipids and loss of cuticle integrity. In addition, sdg8 and sdg25 mutants were impaired in H2B ubiquitination (H2Bubn) at CCR2, CER3, and H2Bubn regulated R gene, SNC1, revealing crosstalk between the two types of histone modifications. In summary, SDG8 and SDG25 contribute to plant immunity directly through HLM or indirectly through H2Bubn and by regulating expression of plant immunity genes, accumulation of lipids, biosynthesis of carotenoids, and maintenance of cuticle integrity. PMID- 27354554 TI - Evolutionarily Distinct BAHD N-Acyltransferases Are Responsible for Natural Variation of Aromatic Amine Conjugates in Rice. AB - Phenolamides (PAs) are specialized (secondary) metabolites mainly synthesized by BAHD N-acyltransferases. Here, we report metabolic profiling coupled with association and linkage mapping of 11 PAs in rice (Oryza sativa). We identified 22 loci affecting PAs in leaves and 16 loci affecting PAs in seeds. We identified eight BAHD N-acyltransferases located on five chromosomes with diverse specificities, including four aromatic amine N-acyltransferases. We show that genetic variation in PAs is determined, at least in part, by allelic variation in the tissue specificity of expression of the BAHD genes responsible for their biosynthesis. Tryptamine hydroxycinnamoyl transferase 1/2 (Os-THT1/2) and tryptamine benzoyl transferase 1/2 (Os-TBT1/2) were found to be bifunctional tryptamine/tyramine N-acyltransferases. The specificity of Os-THT1 and Os-TBT1 for agmatine involved four tandem arginine residues, which have not been identified as specificity determinants for other plant BAHD transferases, illustrating the versatility of plant BAHD transferases in acquiring new acyl acceptor specificities. With phylogenetic analysis, we identified both divergent and convergent evolution of N-acyltransferases in plants, and we suggest that the BAHD family of tryptamine/tyramine N-acyltransferases evolved conservatively in monocots, especially in Gramineae. Our work demonstrates that omics-assisted gene to-metabolite analysis provides a useful tool for bulk gene identification and crop genetic improvement. PMID- 27354556 TI - A Sorghum Mutant Resource as an Efficient Platform for Gene Discovery in Grasses. AB - Sorghum (Sorghum bicolor) is a versatile C4 crop and a model for research in family Poaceae. High-quality genome sequence is available for the elite inbred line BTx623, but functional validation of genes remains challenging due to the limited genomic and germplasm resources available for comprehensive analysis of induced mutations. In this study, we generated 6400 pedigreed M4 mutant pools from EMS-mutagenized BTx623 seeds through single-seed descent. Whole-genome sequencing of 256 phenotyped mutant lines revealed >1.8 million canonical EMS induced mutations, affecting >95% of genes in the sorghum genome. The vast majority (97.5%) of the induced mutations were distinct from natural variations. To demonstrate the utility of the sequenced sorghum mutant resource, we performed reverse genetics to identify eight genes potentially affecting drought tolerance, three of which had allelic mutations and two of which exhibited exact cosegregation with the phenotype of interest. Our results establish that a large scale resource of sequenced pedigreed mutants provides an efficient platform for functional validation of genes in sorghum, thereby accelerating sorghum breeding. Moreover, findings made in sorghum could be readily translated to other members of the Poaceae via integrated genomics approaches. PMID- 27354555 TI - Circadian Stress Regimes Affect the Circadian Clock and Cause Jasmonic Acid Dependent Cell Death in Cytokinin-Deficient Arabidopsis Plants. AB - The circadian clock helps plants measure daylength and adapt to changes in the day-night rhythm. We found that changes in the light-dark regime triggered stress responses, eventually leading to cell death, in leaves of Arabidopsis thaliana plants with reduced cytokinin levels or defective cytokinin signaling. Prolonged light treatment followed by a dark period induced stress and cell death marker genes while reducing photosynthetic efficiency. This response, called circadian stress, is also characterized by altered expression of clock and clock output genes. In particular, this treatment strongly reduced the expression of CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY). Intriguingly, similar changes in gene expression and cell death were observed in clock mutants lacking proper CCA1 and LHY function. Circadian stress caused strong changes in reactive oxygen species- and jasmonic acid (JA)-related gene expression. The activation of the JA pathway, involving the accumulation of JA metabolites, was crucial for the induction of cell death, since the cell death phenotype was strongly reduced in the jasmonate resistant1 mutant background. We propose that adaptation to circadian stress regimes requires a normal cytokinin status which, acting primarily through the AHK3 receptor, supports circadian clock function to guard against the detrimental effects of circadian stress. PMID- 27354557 TI - The Slicer Activity of ARGONAUTE1 Is Required Specifically for the Phasing, Not Production, of Trans-Acting Short Interfering RNAs in Arabidopsis. AB - ARGONAUTE1 (AGO1) mediates posttranscriptional silencing by microRNAs (miRNAs) and short interfering RNAS (siRNAs). AGO1-catalyzed RNA cleavage (slicing) represses miRNA targets, but current models also highlight the roles of slicing in formation of siRNAs and siRNA-AGO1 complexes. miRNA-guided slicing is required for biogenesis of phased, trans-acting siRNAs (tasiRNAs), whose cleaved precursor fragments are converted to double-stranded RNA by RNA-dependent RNA polymerase 6 (RDR6). In addition, unwinding of duplex siRNA bound to AGO1 requires passenger strand cleavage in vitro. In this study, we analyze how mutation of four metal ion-coordinating residues of Arabidopsis thaliana AGO1 affects slicer activity in vitro and siRNA function in vivo. We show that while all four residues are required for slicer activity, they do not contribute equally to catalysis. Moreover, passenger strand cleavage is required for assembly of active AGO1-siRNA complexes in vivo, and many AGO1-bound siRNAs are trimmed in the absence of slicer activity. Remarkably, seedlings defective in AGO1 slicer activity produce abundant siRNAs from tasiRNA loci in vivo. These siRNAs depend on RDR6 and SUPPRESSOR OF GENE SILENCING3, but unlike wild-type tasiRNAs, they are unphased. These results demonstrate that slicing is solely required for phase definition of tasiRNAs, and they strongly support recruitment of RDR6 by AGO1 rather than by cleavage fragments. PMID- 27354559 TI - Invisible No Longer: Peptidoglycan in Moss Chloroplasts. PMID- 27354558 TI - Arabidopsis CSLD5 Functions in Cell Plate Formation in a Cell Cycle-Dependent Manner. AB - In plants, the presence of a load-bearing cell wall presents unique challenges during cell division. Unlike other eukaryotes, which undergo contractile cytokinesis upon completion of mitosis, plants instead synthesize and assemble a new dividing cell wall to separate newly formed daughter cells. Here, we mine transcriptome data from individual cell types in the Arabidopsis thaliana stomatal lineage and identify CSLD5, a member of the Cellulose Synthase Like-D family, as a cell wall biosynthesis enzyme uniquely enriched in rapidly dividing cell populations. We further show that CSLD5 is a direct target of SPEECHLESS, the master transcriptional regulator of these divisions during stomatal development. Using a combination of genetic analysis and in vivo localization of fluorescently tagged fusion proteins, we show that CSLD5 preferentially accumulates in dividing plant cells where it participates in the construction of newly forming cell plates. We show that CSLD5 is an unstable protein that is rapidly degraded upon completion of cell division and that the protein turnover characteristics of CSLD5 are altered in ccs52a2 mutants, indicating that CSLD5 turnover may be regulated by a cell cycle-associated E3-ubiquitin ligase, the anaphase-promoting complex. PMID- 27354561 TI - Regulatory principles in metabolism-then and now. AB - The importance of metabolic pathways for life and the nature of participating reactions have challenged physiologists and biochemists for over a hundred years. Eric Arthur Newsholme contributed many original hypotheses and concepts to the field of metabolic regulation, demonstrating that metabolic pathways have a fundamental thermodynamic structure and that near identical regulatory mechanisms exist in multiple species across the animal kingdom. His work at Oxford University from the 1970s to 1990s was groundbreaking and led to better understanding of development and demise across the lifespan as well as the basis of metabolic disruption responsible for the development of obesity, diabetes and many other conditions. In the present review we describe some of the original work of Eric Newsholme, its relevance to metabolic homoeostasis and disease and application to present state-of-the-art studies, which generate substantial amounts of data that are extremely difficult to interpret without a fundamental understanding of regulatory principles. Eric's work is a classical example of how one can unravel very complex problems by considering regulation from a cell, tissue and whole body perspective, thus bringing together metabolic biochemistry, physiology and pathophysiology, opening new avenues that now drive discovery decades thereafter. PMID- 27354560 TI - Protein partners of the calcium channel beta subunit highlight new cellular functions. AB - Calcium plays a key role in cell signalling by its intervention in a wide range of physiological processes. Its entry into cells occurs mainly via voltage-gated calcium channels (VGCC), which are found not only in the plasma membrane of excitable cells but also in cells insensitive to electrical signals. VGCC are composed of different subunits, alpha1, beta, alpha2delta and gamma, among which the cytosolic beta subunit (Cavbeta) controls the trafficking of the channel to the plasma membrane, its regulation and its gating properties. For many years, these were the main functions associated with Cavbeta. However, a growing number of proteins have been found to interact with Cavbeta, emphasizing the multifunctional role of this versatile protein. Interestingly, some of the newly assigned functions of Cavbeta are independent of its role in the regulation of VGCC, and thus further increase its functional roles. Based on the identity of Cavbeta protein partners, this review emphasizes the diverse cellular functions of Cavbeta and summarizes both past findings as well as recent progress in the understanding of VGCC. PMID- 27354562 TI - The growing landscape of tubulin acetylation: lysine 40 and many more. AB - Tubulin heterodimers are the building block of microtubules, which are major elements of the cytoskeleton. Several types of post-translational modifications are found on tubulin subunits as well as on the microtubule polymer to regulate the multiple roles of microtubules. Acetylation of lysine 40 (K40) of the alpha tubulin subunit is one of these post-translational modifications which has been extensively studied. We summarize the current knowledge about the structural aspects of K40 acetylation, the functional consequences, the enzymes involved and their regulation. Most importantly, we discuss the potential importance of the recently discovered additional acetylation acceptor lysines in tubulin subunits and highlight the urgent need to study tubulin acetylation in a more integrated perspective. PMID- 27354563 TI - Degradation of dyes using crude extract and a thermostable and pH-stable laccase isolated from Pleurotus nebrodensis. AB - Three laccase isoenzymes (Lac1, Lac2 and Lac3) have been purified to homogeneity from Pleurotus nebrodensis in our previous study. Lac2 was shown to be the dominant isoform, capable of oxidizing the majority of laccase substrates and manifesting good thermostability and pH stability. Hence, Lac2 was selected to decolourize structurally different dyes and the colour removal efficiencies of Lac2 and the crude extract of P. nebrodensis were compared. By monitoring the lambdamax of the reaction system during the course of biotransformation, clear hypsochromic shifts were observed for most of the dyes examined, illustrating that at least one peak disappeared as a result of laccase treatment. In general, Lac2 was more efficient within a short time (1 h) and the crude extract, in general, could achieve similar or even higher efficiency when the duration of treatment was extended to 24 h. Malachite green (MG) was chosen to study the detoxifying potential of Lac2, because of the relatively simple structure and high toxicity of the dye towards microorganisms. The toxicity of MG towards both bacteria (Bacillus subtilis, Bacillus licheniformis, Pseudomonas fluorescens and Escherichia coli) and fungi (Fusarium graminearum and Trichoderma harzianum) was dramatically decreased and the potential mechanism was estimated by GC-MS as to remove four methyl groups firstly and the two newly formed amine groups would be degraded or polymerized further. The present study facilitates an understanding of the application of P. nebrodensis laccases and furnishes evidence for the safety of their utilization in the treatment of wastewater emanating from textile industries. PMID- 27354564 TI - MicroRNA-720 suppresses M2 macrophage polarization by targeting GATA3. AB - Macrophages are highly plastic cells with the ability to differentiate into both M1- and M2-polarized phenotypes. As a distinct M2-polarized population, tumour associated macrophages (TAMs) promote tumorigenesis owing to their pro-angiogenic and immune-suppressive functions in tumour microenvironment. In the present study, we found that the microRNA-720 (miR-720) was down-regulated in TAMs isolated from breast carcinomas and M2-polarization macrophages. Overexpression of miR-720 attenuated M2 phenotype expression and thus inhibited M2 polarization. We further identified GATA binding protein 3 (GATA3), a transcriptional factor that plays an important role in M2 macrophage polarization, was the downstream target of miR-720 Ectopic expression of GATA3 restored the M2 phenotype in miR 720 overexpressed macrophages. Importantly, overexpression of miR-720 inhibited pro-migration behaviour and phagocytic ability of M2-polarized macrophages. Thus, our data suggest that miR-720 plays an important role in regulating M2 macrophage polarization and function. PMID- 27354565 TI - Putting pontine anatomy into clinical practice: the 16 syndrome. AB - The anatomical localisation of brainstem syndromes is the domain of the clinical neurologist, though MRI has made an encyclopaedic knowledge of neuroanatomy less crucial. Isolated pontine syndromes comprise ~20% of the brainstem lacunar syndromes. Typical presentations such as pure motor hemiparesis and ataxic hemiparesis are easily recognisable but atypical syndromes, particularly when bilateral, may present with puzzling signs. We discuss a patient with an unusual acute bilateral brainstem syndrome, in whom MRI was contraindicated. We use the relevant neuroanatomy to support the likely diagnosis of bilateral caudal pontine tegmentum infarction due to occlusion of a single paramedian pontine tegmental perforating artery. PMID- 27354567 TI - Commentary. PMID- 27354568 TI - Commentary. PMID- 27354566 TI - Pheochromocytoma Masked by Mutation in the TH Gene. PMID- 27354570 TI - The Case of the Purple Urinary Collection Bag. PMID- 27354569 TI - Comparison of 3 Methodologies for Genotyping of Small Deletion and Insertion Polymorphisms. AB - BACKGROUND: The quantification of genomic chimerism is increasingly recognized for its clinical significance after transplantation. Before the measurement of chimerism, accurate genotyping of genetic polymorphisms for informative alleles that can distinguish donor DNA from recipient DNA is essential. The ease of allelic discrimination of small deletion and insertion polymorphisms (DIPs) makes DIPs attractive markers to track chimerism. Current methodologies for the genotyping of DIPs are largely based on "open-tube" approaches. "Closed-tube" approaches involving no or minimal post-PCR handling are preferred. We compared 3 distinct methodologies to determine an optimal platform for DIP genotyping. METHODS: Genomic DNA from 19 normal individuals was genotyped for 6 small biallelic DIPs using high-resolution melting analysis (HRMA), probe-free droplet digital PCR (ddPCR), and microfluidic electrophoresis of PCR products. For HRMA, 3 different platforms were compared. RESULTS: Our newly developed probe-free ddPCR approach allowed the genotype of each DIP to be determined by fluorescence intensity based on amplicon size. Microfluidic electrophoresis also allowed genotypes to be determined by amplicon size. HRMA assays allowed the genotype of each DIP to be determined by melting profile. Genotyping results were concordant between the 3 methodologies. HRMA was the most readily performed methodology and was robust across 3 separate HRMA-capable platforms. CONCLUSIONS: We demonstrated the effectiveness of probe-free ddPCR to accurately genotype small biallelic DIPs. Nevertheless, HRMA proved to be the optimal approach for genotyping small DIPs because closed-tube approaches are preferred owing to rapid and less laborious workflows and least risk of PCR contamination. PMID- 27354571 TI - What's Missing? PMID- 27354572 TI - How Does Obesity Affect an Individual's Chances of Developing Cancer? PMID- 27354573 TI - All Biomedical and Health Science Researchers, Including Laboratory Physicians and Scientists, Need Adequate Education and Training in Study Design and Statistics. PMID- 27354575 TI - Measuring Adherence to HIV Pre-Exposure Prophylaxis through Dried Blood Spots. PMID- 27354576 TI - English Countryside on a Sunny Day in Spring. PMID- 27354577 TI - Cinema: Its Surreptitious Service to Science. PMID- 27354579 TI - Current Status of Biological Therapies for the Treatment of Metastatic Melanoma. AB - Compared to early-stage melanoma when surgical excision is possible, metastatic disease continues to offer a much grimmer prognosis as traditional chemotherapy treatment regimens offer relatively little survival benefit. This has led to changes in treatment approaches over the preceding two decades as contemporary methods for the treatment of advanced or metastatic melanoma now involve a number of biological modalities, which include immunotherapeutic approaches, targeted therapies and epigenetic modification therapies. Clinically available immunotherapeutic agents include interleukin 2 (IL-2), as well as drugs targeting the important immune checkpoint molecules, such as cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). The targeted therapeutic agents modulate specific pro-oncogenic mutations such as v Raf murine sarcoma viral oncogene homolog B (BRAF), receptor tyrosine kinases, MEK inhibitors and potential future therapeutic targets, such as the CDK4/CDK6, PTEN and GNAQ/GNA11 genes. Additionally, an increasing understanding of the role of epigenetic alterations in the development and progression of melanoma now offers a new potential drug target. Several of these agents have shown promising results; however, in many investigations, combinations of different therapeutic approaches, each with different mechanisms of action, have yielded improved outcomes as treatment regimens continue to be further optimized by active research and patient disease sub-group analyses. This review summarizes the novel biological agents and new treatments, directly contributing to the significant improvement of biological therapies and markedly advancing knowledge of clinical application of newly approved and developed therapies in treatment of patients with metastatic melanoma. PMID- 27354580 TI - The Use of Complementary and Alternative Medicine in Scandinavia. AB - BACKGROUND: Complementary alternative medicine (CAM) is widely used among patients with cancer. This usage may have potentially harmful effects, especially when combined with anticancer drugs. However, some complementary methods may benefit patients. This review investigated the prevalence of CAM use among patients with cancer in Scandinavia and secondly studied the educational levels of CAM users compared to non-users. MATERIALS AND METHODS: A systematic search of the PubMed library was carried out to locate articles published between January 2000 and October 2015 that investigated prevalence of CAM use among Scandinavian patients with cancer. RESULTS: Twenty-two articles were found, of which nine were included in the review. The prevalence of CAM use was 7.9% to 53%, with an average of 36.0% across all studies. CONCLUSION: Use of CAM is widespread among patients with cancer. Knowledge about CAM should be disseminated to both patients and staff in order to optimise discussions about CAM in clinical practice. PMID- 27354581 TI - Non-routine Tracers for PET Imaging of High-grade Glioma. AB - Thorough imaging is crucial for diagnosis and treatment of high-grade gliomas (HGG), lethal brain tumours with median survival ranging 1-5 years after diagnosis. Positron-emission tomography (PET) is acquiring importance in imaging of HGG since it has the formidable advantage of providing information on tumour metabolism that may be critical for correct diagnosis and treatment planning. Recently employed PET tracers designed for the non-routine investigation of specific aspects of HGG metabolism, including hypoxia, neoangiogenesis, expression of integrins and stem cell markers, are reviewed herein. A thorough choice from among these non-routine tracers may provide important metabolic information complementing those obtained with more common PET analyses, for the sake of diagnostic, prognostic, treatment planning or research purposes. PMID- 27354582 TI - Premalignant Oral Lesion Cells Elicit Increased Cytokine Production and Activation of T-cells. AB - BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) are known to evade the host immune response. How premalignant oral lesions modulate the immune response, however, has yet to be elucidated. MATERIALS AND METHODS: A mouse model of oral carcinogenesis was used to determine how mediators from premalignant oral lesion cells vs. HNSCC cells impact on immune cytokine production and activation. RESULTS: Media conditioned by premalignant lesion cells elicited an increased production of T cell-associated cytokines and proinflammatory mediators from cervical lymph node cells compared to media conditioned by HNSCC cells or media alone. In the presence of premalignant lesion cell-conditioned media, CD4(+) T cell expression of the IL-2 receptor CD25 and CD8(+) T cell expression of the activation marker CD69 was greater, compared to what was induced in HNSCC cell conditioned media or media alone. CONCLUSION: Premalignant lesion cells promote a proinflammatory environment and induce immune changes before HNSCC tumors are established. PMID- 27354583 TI - Delivery of siRNA Using Cationic Liposomes Incorporating Stearic Acid-modified Octa-Arginine. AB - Cationic liposomes incorporating stearic acid-modified octa-arginine (StA-R8) were evaluated for survivin small interfering RNA (siRNA) delivery. StA-R8 was synthesized and incorporated into liposomes. The composition of liposomes was optimized. Physicochemical properties, cytotoxicity, cellular uptake and gene silencing activity of the liposomes complexed to survivin siRNA were investigated. The results showed that StA-R8-containing liposomes had reduced cytotoxicity and improved delivery efficiency of siRNA into cancer cells compared with StA-R8 by itself. PMID- 27354584 TI - Profiling of Vascular Endothelial Growth Factor Receptor Heterogeneity Identifies Protein Expression-defined Subclasses of Human Non-small Cell Lung Carcinoma. AB - BACKGROUND: the vascular endothelial growth factor (VEGF) pathway plays a prominent role in the growth and progression of human cancer, including non-small cell lung carcinoma (NSCLC). The key mediators of VEGF signaling are a family of related receptor tyrosine kinases that include VEGFR1, VEGFR2, and VEGFR3. The relative expression levels, activity, and cross-talk among these receptors may contribute to response of NSCLC to anti-angiogenic therapies, and a better systematic, translatable approach to categorizing tumors is needed. MATERIALS AND METHODS: We comparatively evaluated immunohistochemical expression of the three VEGFRs in archival primary NSCLC tissues (n=96). RESULTS: VEGFR1 and VEGFR2 were localized both in vessels and tumor cells, while VEGFR3 was only localized in tumor vessels. A set of eight VEGFR staining subclasses were identified: Triple VEGFR positive (n=11, 11.5%), VEGFR1 predominant (n=22, 22.9%), VEGFR2 predominant (n=9, 9.4%), VEGFR3 predominant (n=3, 3.1%), VEGFR1/2 predominant (13, 13.5%), VEGFR1/3 predominant (2, 2.1%), VEGFR2/3 predominant (n=8, 8.3%), and triple VEGFR negative (n=28, 29.2%). An objective categorization based on K means clustering revealed four clusters, three of which showed high VEGFR2 compared to VEGFR3 (30.7% of cases), cases high in both VEGFR2 and VEGFR3 (18.2%), and cases that were negative/low for both VEGFR2 and VEGFR3 (45.4%). A positive association between VEGFR2 and VEGFR3 was found, however no associations were observed between VEGFR1 and VEGFR2, nor VEGFR1 and VEGFR3. CONCLUSION: The proposed subclasses of NSCLC are an approach for complementing lines of investigation of anti-angiogenic therapies beginning with systematic characterization of the disease. PMID- 27354585 TI - Histone Methylation by Temozolomide; A Classic DNA Methylating Anticancer Drug. AB - BACKGROUND/AIM: The alkylating agent, temozolomide (TMZ), is considered the standard-of-care for high-grade astrocytomas -known as glioblastoma multiforme (GBM)- an aggressive type of tumor with poor prognosis. The therapeutic benefit of TMZ is attributed to formation of DNA adducts involving the methylation of purine bases in DNA. We investigated the effects of TMZ on arginine and lysine amino acids, histone H3 peptides and histone H3 proteins. MATERIALS AND METHODS: Chemical modification of amino acids, histone H3 peptide and protein by TMZ was performed in phosphate buffer at physiological pH. The reaction products were examined by mass spectrometry and western blot analysis. RESULTS: Our results showed that TMZ following conversion to a methylating cation, can methylate histone H3 peptide and histone H3 protein, suggesting that TMZ exerts its anticancer activity not only through its interaction with DNA, but also through alterations of protein post-translational modifications. CONCLUSION: The possibility that TMZ can methylate histones involved with epigenetic regulation of protein indicates a potentially unique mechanism of action. The study will contribute to the understanding the anticancer activity of TMZ in order to develop novel targeted molecular strategies to advance the cancer treatment. PMID- 27354586 TI - Inhibitory Effect of Anti-rheumatic Drug Iguratimod for Hepatocellular Carcinogenesis by Inhibition of Serum Interleukin-8 Production. AB - BACKGROUND/AIM: Angiogenesis is a known factor for the development of hepatocellular carcinoma (HCC). The aim of this study was to assess the property of iguratimod, that is an anti-inflammatory drug for rheumatoid arthritis, on anti-angiogenesis and anti-carcinogensis for HCC. MATERIALS AND METHODS: In vitro, human umbilical vein endothelial cells were cultured under interleukin-8 (IL-8) with or without iguratimod. In vivo, a rat model with HCC received iguratimod or distilled water for 6 weeks. Diameter of the largest tumor, number of tumors and serum interleukin-8 concentration were compared between iguratimod and control groups. RESULTS: By an in vitro angiogenesis assay, it was found angiogenesis in iguratimod group was significantly lower than that in control group (p=0.013). In vivo, largest tumor diameter (p=0.036), number of the tumor (p=0.011) and serum interleukin-8 concentration (p=0.036) in the iguratimod group were significantly smaller and lower than those in the control group. CONCLUSION: Iguratimod may inhibit hepatocellular carcinogensis by inhibition of interleukin 8 production in a rat model. PMID- 27354587 TI - 1alpha,25(OH)2D3 Analog, MART-10, Inhibits Neuroendocrine Tumor Cell Growth Through Induction of G0/G1 Cell-cycle Arrest and Apoptosis. AB - BACKGROUND: Neuroendocrine tumors (NETs) are the second most common digestive malignancy. For advanced NETs, survival is not satisfactory. Vitamin D has emerged as a promising anticancer drug. MATERIALS AND METHODS: Cell proliferation assay, western blot, flow cytometry, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays were applied. RESULTS: We demonstrated that RIN-m cells, neuroendocrine tumor cells, expressed vitamin D receptor (VDR) and VDR expression increased with increasing exposure to 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] or MART-10, a 1alpha,25(OH)2D3 analog. MART-10 had anti growth effect on RIN-m cells comparable to those of 1alpha,25(OH)2D3 The growth inhibition of both drugs was mediated by induction of cell-cycle arrest at G0/G1 phase and apoptosis. Western blot assay further revealed that this G0/G1 arrest was due to the up-regulation of p27 and down-regulation of cyclin dependent kinase 4 (CDK4), with MART-10 also reducing CDK6. Apoptosis induction was further supported by increased cleaved caspase-3 expression after treatment. CONCLUSION: MART-10 appears to be a promising regimen for NET treatment. PMID- 27354588 TI - bFGF Up-regulation Reduces Spontaneous Necrosis of VX2 Tumors Without Increasing Tumoral Microvascular Density. AB - AIM: To determine whether up-regulation of basic fibroblast growth factor (bFGF) in VX2 cells reduces tumor necrosis. MATERIALS AND METHODS: VX2 cells were transfected with expression vector containing cDNA of rabbit bFGF. Stable clones producing rabbit bFGF (bFGF-VX2) were selected. bFGF-VX2 (n=5) or non-transfected VX2 (control) (n=5) cells were implanted into leg muscle of 10 rabbits. The tumors were characterized 21 days after grafting. RESULTS: Overexpression of bFGF by VX2 tumors significantly reduced necrosis (p<0.0223) and increased cell viability (p<0.0223), without effect on the mean vascular density. bFGF concentration was significantly higher in bFGF-VX2 tumors (p<0.0062) and negatively correlated with tumor volume at day 21 (rho=-0.927, p<0.0034). Vascular endothelial growth factor concentration was significantly lower in bFGF VX2 tumors (p<0.0105) and negatively correlated with the bFGF concentration of tumors (rho=-0.903, p<0.0067). CONCLUSION: The overexpression of bFGF in VX2 cells increased tumor viability and reduced necrosis, making the evaluation of long-term anticancer therapies possible in this model. PMID- 27354589 TI - Drug-induced Modulation of Heat Shock Protein HSPB1 in an Ovarian Cancer Cell Model. AB - BACKGROUND: Heat-shock protein HSPB1 (alternative name HSP27) plays a pivotal role in cell survival pathways, apoptosis, metastasis and has been frequently linked to treatment resistance in ovarian cancer (OC) and other malignancies. Characteristic HSPB1 induction in different solid tumors is often caused by cytotoxic agents. MATERIALS AND METHODS: An in vitro OC cell model system was established to characterize resistance mechanisms during chemotherapy. Human OC cell lines OVCAR-3, SK-OV-3 and TOV-21G were treated with paclitaxel or carboplatin. Cellular growth was analyzed by cell counting. Intra- and extracellular HSPB1 concentrations were assessed by western blot and enzyme linked immunosorbent assays. RESULTS: Incubation with paclitaxel, and with carboplatin significantly reduced cell growth without a definitive increase of intracellular HSPB1 expression. HSPB1 demonstrated drug-inducible secretion into the extracellular compartment. CONCLUSION: Despite its current lack of analysis in patient samples, serum soluble HSPB1 may function as a specific biomarker for monitoring response to chemotherapy in patients with OC. PMID- 27354590 TI - The Tumor Suppressor MicroRNA-1 Exhibits Restricted Inhibition of Proliferation of Ovarian Cancer Cells. AB - BACKGROUND: MicroRNAs are able to control vital tumor biological processes, such as proliferation, tissue transformation and cell migration, as well as apoptosis. One of the micro RNAs, namely miR-1, has been classified as a tumor suppressor, however, preliminary data did not confirm this finding in ovarian cancer (OC) cells. This study examined the impact of miR-1 on OC cell growth. MATERIALS AND METHODS: Recombinant miR-1 was overexpressed in human OC cell lines OVCAR-3, SK OV-3, TOV-112D, and TOV-21G. Subsequently, cell growth was analyzed. RESULTS: After transfection, 11- to 487-fold overexpression of miR-1 was detectable in the OC cells. However, no significant differences in proliferation compared to control cells were detected, neither in transiently nor in stably transfected cells. CONCLUSION: In numerous cancer entities miR-1 is defined as an antiproliferative tumor suppressor. Notably, the present study demonstrated a loss of growth-inhibitory functionality of miR-1 by so far unknown mechanisms, suggesting dysregulated miR-1 signaling or effector cascades in OC cells. PMID- 27354591 TI - Contribution of Matrix Metallopeptidase-1 Genotypes, Smoking, Alcohol Drinking and Areca Chewing to Nasopharyngeal Carcinoma Susceptibility. AB - BACKGROUND/AIM: The up-regulation of matrix metalloproteinase-1 (MMP-1) has been demonstrated to be correlated with lymph node metastasis of nasopharyngeal carcinoma (NPC); however, the genotypic role of MMP-1 is not well understand. The present study aimed to assess the contribution of MMP-1 promoter -1607 genotypes, combined with environmental carcinogens, on the predisposition to NPC tumorigenesis. MATERIALS AND METHODS: The MMP-1 promoter -1607 genotypes were examined for 352 age- and gender-matched controls and 176 NPC patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: We found that the MMP-1 promoter -1607 heterozygous 1G/2G and homozygous 1G/1G genotypes, were more and more prone to be associated with NPC risk (odds ratio (OR)=0.64 and 0.63, 95% confidence interval (CI)=0.43-1.03 and 0.36-0.96, p=0.0659 and 0.0932, respectively). In the dominant models, there was a significant association between the genotype of MMP-1 promoter -1607 and NPC risk (OR=0.64, 95% CI=0.43-0.91, p=0.0359). In addition, individuals carrying the 1G allele at MMP-1 promoter -1607 were less susceptible to NPC (OR=0.73; 95%CI=0.59 to 0.96, p=0.0418) after adjustment for age, gender, cigarette, alcohol and areca consumption. CONCLUSION: The 1G/1G genotype of MMP-1 promoter 1607 may independently have a protective effect on NPC risk, without interaction with behavioral factors, including cigarette, alcohol and areca consumption. PMID- 27354592 TI - Matrix Metalloproteinase-1 Genetic Polymorphism in Breast Cancer in Taiwanese. AB - AIM: Metalloproteinases (MMPs) are a family of enzymes involved in many physiological processes, such as skeletal development, wound healing, and scar formation, as well as carcinogenesis. However, the contribution of MMP1 genotype to breast cancer has not been elucidated. This study aimed to evaluate the contribution of commonly studied MMP1 promoter 1607 genotype to breast cancer risk. MATERIALS AND METHODS: In this hospital-based case-control study, contribution of MMP1 genotype to breast cancer risk was evaluated among 1,232 patients with breast cancer and 1,232 gender-matched healthy controls. RESULTS: The distribution of 2G/2G, 1G/2G and 1G/1G for MMP1 promoter 1607 genotype was 36.0%, 41.3% and 22.7% in the breast cancer group and 34.2%, 44.5% and 21.3% in the non-cancer group, respectively (p for trend=0.2820). We also analyzed the allelic frequency distributions and found that the variant 1G allele of MMP1 promoter 1607 conferred similar breast cancer susceptibility as the wild-type 2G allele (odds ratio=0.99, 95% confidence interval=0.89-1.11, p=0.8858). There was no interaction between MMP1 promoter 1607 genotype and cigarette smoking or alcohol drinking habits. CONCLUSION: The genotype of MMP1 promoter 1607 may not be a major determining factor for breast cancer risk. The contribution of MMP1 promoter 1607 genotype to prognosis and subtypes of breast cancer needs further investigation. PMID- 27354593 TI - alpha-Hexylcinnamaldehyde Synergistically Increases Doxorubicin Cytotoxicity Towards Human Cancer Cell Lines. AB - AIM: alpha-Hexylcinnamaldehyde (HCA), a compound derived from cinnamaldehyde, was evaluated for its potential chemosensitizing properties. MATERIALS AND METHODS: The cytotoxicity of HCA was tested against Caco-2, CCRF/CEM and CEM/ADR5000 human cancer cells. Furthermore, its ability to increase doxorubicin cytotoxicity was evaluated in combination assays. Rhodamine123 efflux assay was carried out in order to highlight the possible interference of HCA with functionality of ATP binding cassette (ABC)-transporters. RESULTS: In spite of a low cytotoxicity, HCA increased the antiproliferative effect of doxorubicin in all the cell lines tested, being particularly effective in CCRF/CEM. The compound also reduced the rhodamine123 efflux in Caco-2 and CEM/ADR5000 cells, suggesting a possible interference with ABC transporter functionality. CONCLUSION: Considering that the greatest synergism between HCA and DOX was found against CCRF/CEM cells (lacking ABC pumps), it seems likely that non-specific mechanisms, including the alteration of membrane permeability, could be involved in the chemosensitizing effect of HCA. PMID- 27354594 TI - Impact of Genetic Variation in MicroRNA-binding Site on Susceptibility to Colorectal Cancer. AB - The present study analyzed single nucleotide polymorphisms (SNPs) located at putative microRNA(miRNA)-binding sites of the 3'-untranslated region (UTR) in different genes and investigated their impact on the susceptibility to colorectal cancer (CRC). Ninety-two SNPs were selected using an in silico analysis of 3'-UTR SNPs in an SNP database and their miRNA binding efficiency was calculated using several miRNA databases and the HapMap database. Two independent study sets were used: 380 healthy controls and 371 patients with colorectal adenocarcinoma for the discovery set, and 521 healthy controls and 524 patients with colorectal adenocarcinoma for the validation set. The SNP genotyping was performed using a Sequenom MassARRAY. In addition, a luciferase assay was used to investigate whether miR-370 modulated docking protein 3 (DOK3) gene expression when rs2279398G>A was included in the DOK3 3'-UTR region. For the discovery set, 16 out of 92 SNPs were significantly associated with the risk of CRC in at least one of the genetic models. The validation set showed that among these 16 SNPs, DOK3 rs2279398G>A was significantly associated with reduced risk of CRC in a recessive model [adjusted odds ratio (aOR)=0.65, 95% confidence interval (CI)=0.44-0.97, p=0.03]. In a combined analysis, DOK3 rs2279398G>A was associated with a significantly reduced risk of CRC in a co-dominant and recessive model (aOR=0.84, 95% CI=0.73-0.96, p=0.012; aOR=0.65, CI=0.49-0.88, p=0.004, respectively). Significantly lower Renilla activity was also observed with the rs2279398 AA construct when compared to the rs2279398 GG construct (p<0.001). DOK3 rs2279398G>A may affect the expression of DOK3 by altering the miRNA binding efficiency at the miRNA-binding sites of the 3'-UTR in DOK3, thereby impacting CRC tumorigenesis. PMID- 27354595 TI - Photodynamic Therapy Potentiates the Effects of Curcumin on Pediatric Epithelial Liver Tumor Cells. AB - BACKGROUND/AIM: Curcumin (CUM) is a promising agent in complementary oncology. The present study analyzed the photoactive properties of curcumin on pediatric epithelial liver tumor cell lines. MATERIALS AND METHODS: Hepatoblastoma cell lines (HuH6, HepT1) and hepatocellular carcinoma cell lines (HepG2, HC-AFW1) were treated with curcumin and exposed to blue light (phototherapy, 480 nm, 300 W). Cell viability (MTT tests), cellular oxidative stress (production of reactive oxygen species (ROS)) and cellular uptake/degradation of curcumin were analyzed. RESULTS: Significant loss of viability resulted from 24-48 h incubation with curcumin. With photodynamic therapy (PDT), even short time incubation (1 h) with curcumin resulted in significantly lower half maximal inhibitory concentration (IC50) (p<0.001, two-way ANOVA). Significant ROS production was observed with PDT and curcumin. CONCLUSION: Phototherapy strongly enhances the anticancer properties of curcumin in pediatric solid liver tumors in vitro. PMID- 27354596 TI - A Cytokine Cocktail Augments the Efficacy of Adoptive NK-92 Cell Therapy Against Mouse Xenografts of Human Cancer. AB - BACKGROUND/AIM: Peripheral blood mononuclear cells (PBMCs) activated with immobilized monoclonal antibody against cluster of differentiation 3 (CD3) secrete cytokines in their culture supernatant (termed ACD3S). We examined the antitumor efficacy of ACD3S-activated NK-92 cells in vitro and in vivo. MATERIALS AND METHODS: Interleukin (IL) 2-depleted NK-92 cells were reactivated with ACD3S, analyzed for their phenotype and tested for cytotoxicity, and perforin and interferon gamma (IFNgamma) production. Severe combined immunodeficient (SCID) mice xenografted with human melanoma and breast cancer cells were treated with ACD3S-activated NK-92 cells and tumor growth was monitored. RESULTS: Brief activation of IL2-depleted NK-92 cells with ACD3S fully restored their in vitro cytotoxicity towards tumor cells. ACD3S-activated NK-92 cells were phenotypically similar to standard NK-92 cells, but exhibited prolonged cytotoxicity and produced higher levels of IFNgamma. When adoptively transferred to tumor-bearing SCID mice, these cells retarded the growth of melanoma and breast tumors. CONCLUSION: Stimulation of NK-92 cells with ACD3S may be useful in clinical cancer therapy, as an alternative method for ex vivo natural killer cell activation. PMID- 27354597 TI - Enhanced TLR4 Expression on Colon Cancer Cells After Chemotherapy Promotes Cell Survival and Epithelial-Mesenchymal Transition Through Phosphorylation of GSK3beta. AB - BACKGROUND: Phosphorylation of glycogen synthase kinase 3beta (GSK3beta) by phosphatidyl-inositide 3-kinase (PI3K)/protein kinase B (AKT) or inhibition of GSK3beta with small-molecule inhibitor attenuates cell survival and proliferation and increases apoptosis in most cancer cell lines. In this study, we investigated the role of phosphorylated GSK3beta activated by enhanced toll-like receptor 4 (TLR4) expression in drug-treated colon cancer cells as a model of post chemotherapy cancer cells. MATERIALS AND METHODS: The effect of TLR4 stimulation on metastasis and apoptosis in drug-exposed colon cancer cells was determined by real-time polymerase chain reaction (PCR) and immunoblotting. RESULTS: Despite the induction of apoptosis after treatment with oxaliplatin and 5-fluorouracil, lipopolysaccharide (LPS) stimulation via increased TLR4 in drug-treated cancer cells effectively inhibited apoptosis through up-regulation of expression of anti apoptosis-related B-cell lymphoma 2 (BCL2) family proteins [X-linked inhibitor of apoptosis protein (XIAP), BCL2, and survivin] and drug-resistance proteins [multidrug-resistance protein 1 (MDR1), multidrug resistance-associated protein (MRP)1/2/3]. LPS-mediated signaling in drug-treated cancer cells elevated the expression of phosphorylated GSK3beta, extracellular signal-regulated kinase (ERK), and the p65 subunit of nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kappaB). Pharmacological inhibition of GSK3beta (using SB216763) reduced phosphorylation of GSK3beta, re-activated caspase-dependent apoptosis, and blocked the expression of cancer stem cell markers and invasive characteristics in LPS-stimulated drug-treated cells. In addition, the ERK specific inhibitor, PD98059, triggered the apoptosis of TLR4-activated drug exposed colon cancer cells, whereas there was no effect on the expression of epithelial-mesenchymal transition markers or GSK3beta phosphorylation. CONCLUSION: These results suggest that TLR4-induced GSK3beta and ERK phosphorylation independently controls cancer cell survival and regulation of GSK3beta and ERK after chemotherapy, making TLR4 a critical target for reducing drug resistance and metastasis in patients with colon cancer. PMID- 27354598 TI - Clofibrate Demonstrates Efficacy in In Vitro Treatment of Lymphoma and Multiple Myeloma. AB - BACKGROUND/AIM: Multiple myeloma (MM), a hematological malignancy of monoclonal B lymphocytes, remains largely incurable and novel treatments are urgently required. Aberrant activation of wingless-related integration site (WNT)/beta catenin signaling has been demonstrated in both lymphoma and MM, rendering its signaling molecules attractive for the development of new targeted-therapies. Clofibrate has proven anticarcinogenic effects attributed to peroxisome proliferator-activated receptor alpha (PPARalpha) agonism, also affecting WNT associated signaling molecules. MATERIALS AND METHODS: The antitumor apoptotic effect of clofibrate at doses ranging from 0.1-600 MUM was investigated on four human and one murine myeloma cell lines, as well as in two human lymphoma cell lines, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide assay. RESULTS: Clofibrate significantly reduced cell viability in all tested myeloma and lymphoma cell lines in a dose-dependent manner, while healthy cells were hardly affected. CONCLUSION: Given the known safety profile and induction of apoptosis at low effective doses, our data warrant further investigation of clofibrate as a novel therapy agent in MM. PMID- 27354599 TI - Prognostic Significance of NOGO-A/B and NOGO-B Receptor Expression in Malignant Melanoma - A Preliminary Study. AB - BACKGROUND: Neurite outgrowth inhibitor type B (NOGO-B) and its receptor (NGBR) were shown to regulate various crucial cellular processes and may be therefore potential factors influencing carcinogenesis. MATERIALS AND METHODS: Expression of NOGO-A, NOGO-A/B and NGBR was studied in benign melanocytic lesions and primary tumors and metastases of malignant melanoma (MM). RESULTS: Cytoplasmic expression of the studied antigens was detected in melanocytes and MM cells. NOGO A/B expression was significantly lower in metastatatic MM cases compared to primary MM tumors (p<0.01) and bening melanocytic lesions (p<0.001). In primary MM tumors, NOGO-A expression intensity positively correlated with NOGO-A/B (r=0.32, p<0.05) and NGBR expression (r=0.53, p<0.0001). NOGO-B and NGBR immunoreactivity correlated negatively with depth of primary MM infiltration (both p<0.01). Moreover, low NOGO-A/B expression was a factor of poor prognosis of primary MM. CONCLUSION: NOGO-A/B may be a negative prognostic factor of MM. PMID- 27354600 TI - An Immunohistochemical Analysis of PD-L1 Protein Expression in Surgically Resected Small Cell Lung Cancer Using Different Antibodies and Criteria. AB - BACKGROUND: Programmed cell death ligand 1 (PD-L1) expression in lung cancer appears to be important in immunotherapy, as its expression can predict responses to programmed cell death-1 (PD-1)-blocking antibodies. However, a definitive antibody and cut-off value for PD-L1 expression are urgently needed. MATERIALS AND METHODS: The PD-L1 expression in 40 surgically resected small cell lung cancer (SCLC) specimens was evaluated by immunohistochemistry (IHC) with three different antibodies: clones E1L3N, 28-8, and SP142, and using three different evaluations: the Allred score, 1% cut-off, and 5% cut-off. RESULTS: The percentage of tumors with positive PD-L1 expression was inconsistent in the IHC evaluations using the Allred score and 1% cut-off. However, the IHC evaluations using the 5% cut-off showed similar rates of expression using the three different antibodies. CONCLUSION: The results of this study provided detailed evidence on the frequency of PD-L1 expression in surgically resected SCLC, which may be a useful reference for identifying patients with PD-L1-expressing SCLC. PMID- 27354601 TI - Early Experience with 70-150 MUm Irinotecan Drug-eluting Beads (M1-DEBIRI) for the Treatment of Unresectable Hepatic Colorectal Metastases. AB - AIM: To report our early experience on the feasibility and safety of 70-150 MUm drug-eluting beads loaded with irinotecan (M1-DEBIRI) for treating unresectable hepatic colorectal metastases. PATIENTS AND METHODS: An Institutional Review Board-approved, prospectively maintained, multi-institutional registry was evaluated from 2/2009 to 8/2013. Fifteen consecutive patients presenting with liver-dominant metastatic colorectal cancer were treated with M1-DEBIRI. Kaplan Meier statistics was used to evaluate hepatic progression-free-survival and overall survival. RESULTS: Fifteen patients underwent 32 DEBIRI treatments. The mean prescribed dose was 100 mg of irinotecan (range=100-200 mg). In 75% of treatments (n=24), 100% of the prescribed dose was delivered before complete stasis. In 97% of treatments (n=31), at least 50% (median 100 mg, range 25-150 mg) of the prescribed dose was delivered. There was grade 2 abdominal pain after one treatment (3%). In another patient, increased total bilirubin (1.1 to 3.1 mg/dl) was seen after one treatment. There was 42% reduction in median carcinoembryonic antigen level and 33% (5/15 patients) with Response Evaluation Criteria in Solid Tumors (RECIST) objective response (complete and partial). Modified RECIST and European Association for the study of the Liver (EASL) objective response rates were both 73% (11/15 patients). The disease control rate was 93% (14/15 patients). Hepatic progression-free-survival and overall survival were 8 and 13 months respectively. Disease in one patient was down-staged to resection (6%). CONCLUSION: M1-DEBIRI appears to be safe and feasible in the treatment of metastatic colorectal cancer. Smaller beads also provide efficient irinotecan dose delivery. Larger studies are needed to validate these findings. PMID- 27354602 TI - Impact of Endoscopic Indocyanine Green Fluorescence Imaging on Superselective Intra-arterial Chemotherapy for Recurrent Cancer of the Skull Base. AB - BACKGROUND/AIM: For advanced paranasal sinus cancer, intra-arterial (I-A) chemotherapy has been applied for improving prognosis and organ preservation. While computed tomographic angiography (CTA) is useful for identifying the tumor feeding artery, CTA cannot always detect the precise artery. The aim of this study was to assess the feasibility of endoscopic ICG (indocyanine green) fluorescence technique during I-A chemotherapy for recurrent skull-base cancer. PATIENTS AND METHODS: Seven patients with recurrent skull-base cancer were included in this study. Conventional CTA followed by ICG was administered. Additional information regarding tumor-feeding arteries attained via ICG was evaluated. RESULTS: Out of seven cases, the blood supply to the cancer was detected in three by CTA alone. By adding the endoscopic evaluation, the blood supply to the tumor was confirmed without difficulty in all cases. The information from endoscopic fluorescence imaging was helpful in making decisions concerning the administration of drugs for skull-base cancer. CONCLUSION: Endoscopic ICG fluorescence imaging combined with I-A chemotherapy compensated for deficiencies of CTA and generated more useful information about the feeders to tumors than was previously available. PMID- 27354603 TI - Cancer Stem Cell Properties as Factors Predictive of Chemoresistance in Neoadjuvantly-treated Patients with Ovarian Cancer. AB - BACKGROUND/AIM: The nuclear factor erytheroid 2-related factor 2-kelch-like ECH associated protein (NRF2-KEAP1) system and stem cell-like cancer cells are associated with platinum resistance in ovarian cancer. Our objective was to investigate the possible association between platinum resistance, cellular redox state regulation and stem cell properties in ovarian cancer. PATIENTS AND METHODS: Thirty-eight patients with epithelial ovarian cancer were included. All patients had undergone primary diagnostic laparoscopy, platinum-based neoadjuvant chemotherapy, and debulking surgery. Tumor samples were analyzed for NRF2, KEAP1, protein deglycase 1 (DJ1/PARK7), cluster of differentiation molecules 44 (CD44) and 117 (CD117) and aldehyde dehydrogenase 1 (ALDH1) by immunohistochemistry. RESULTS: Positive pre-treatment expression of CD44 (p=0.013) and stable/increased post-therapy CD44 expression were associated with platinum resistance (p=0.001). Negative pre-treatment expression of cytoplasmic ALDH1 predicted sensitivity to platinum (p=0.017). Pre-treatment nuclear KEAP1 expression was greater in stage II-III cancer (p=0.0003). After neoadjuvant treatment, all samples were nuclear KEAP1-positive (p=0.025) and increased nuclear KEAP1 expression was associated with higher tumor stage (p=0.0001). CONCLUSION: CD44 and cytoplasmic ALHD1 could be potential indicators of platinum resistance during neoadjuvant chemotherapy for ovarian cancer. PMID- 27354604 TI - Male Malignant Phyllodes Breast Tumor After Prophylactic Breast Radiotherapy and Bicalutamide Treatment: A Case Report. AB - Phyllodes tumor in male breast is an exceptionally rare neoplasm with only few published case reports. Herein, we present a case of malignant phyllodes tumor in male breast nine years after prophylactic breast 10 Gy radiotherapy and after nine year bicalutamide treatment. The imaging findings of the tumor and pathological correlation are also presented. PMID- 27354605 TI - Bi-weekly Capecitabine-Oxaliplatin (XELOX) plus Bevacizumab as First-line Treatment of Metastatic Colorectal Cancer -The PHOENiX Trial. AB - AIM: This phase II study assessed the efficacy and toxicity of an intermittent weekly capecitabine regimen in combination with oxaliplatin (XELOX) plus bevacizumab as a first-line treatment of metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with measurable mCRC who were to receive first line chemotherapy were enrolled onto this disease-oriented multicenter phase II trial. Patients with mCRC were required to have Eastern Cooperative Oncology Group performance status of 0 to 1, to be aged >20 years, and to have adequate organ function. Localization of tumor, toxicities, response rate, progression free survival (PFS) and time to progression (TTP) were studied. Capecitabine dose was 2,500 mg/m(2)/day on days 1-7 (n=47) and was increased to 3,000 mg/m(2)/day (n=5) in combination with oxaliplatin (85 mg/m(2)) and bevacizumab (5 mg/kg), repeated every 2 weeks. RESULTS: A total of 51 patients were enrolled from 14 institutions from December 2011 to July 2012. The median age was 66 (range=38-85) years, 29 (56.9%) had colonic cancer and 22 (43.1%) had rectal cancer in this study. Pertinent grade 3/4 toxicities were neutropenia (13.7%), peripheral neuropathy (13.7%), hypertension (13.7%), gastrointestinal perforation (3.9%), and hand-foot syndrome (5.9%). The response rate was 51% (one complete and 25 partial responses). Median PFS and TTP were 344 days and 196 days, respectively. Median overall survival has not been reached yet. CONCLUSION: The first-line treatment of mCRC using a biweekly combination of XELOX plus bevacizumab can also be administered safely and effectively in Japan. It is suggested that this regimen is an appropriate option for the treatment of mCRC. PMID- 27354606 TI - Endometriosis-associated Ovarian Cancer: A Distinct Clinical Entity? AB - AIM: The aim of the study was to evaluate the incidence of endometriosis associated ovarian cancer (EAOC) and compare clinicopathological characteristics and overall survival (OS) between patients with EAOC and those with ovarian cancer not associated with endometriosis. PATIENTS AND METHODS: We identified EAOC among 203 patients with invasive epithelial ovarian cancer who underwent complete surgery at our Institution from January 2004 to March 2014. RESULTS: EAOC was present in 45 patients. EAOC was significantly more frequently diagnosed at an earlier stage of disease (p=0.038). At a median follow-up time of 32 months, OS among patients with EAOC was significantly longer (p=0.039). However, stratifying by stage, the OS advantage of EAOC was not significant. At multivariate analysis, only stage was an independent prognostic factor for OS (hazard ratio=5.7; 95% confidence interval=1.8-18.6; p=0.003). CONCLUSION: EAOC incidence was 22.2%. EAOC appears to be diagnosed at an earlier stage and confers a better OS. However, stratifying by stage, the advantage in survival of EAOC disappears. PMID- 27354607 TI - Treatment: Outcome and Toxicity of Volumetric Modulated Arc Therapy in Oropharyngeal Carcinoma. AB - BACKGROUND/AIM: Radiotherapy is a common approach for treating squamous cell carcinoma (SCC) of the oropharynx. We aimed to analyze toxicity and outcome of patients affected by oropharyngeal SCC treated with volumetric modulated arc therapy (VMAT). PATIENTS AND METHODS: Fifty-four patients presenting advanced orophayngeal carcinoma who were treated with radical radiotherapy were analyzed. All patients were treated with VMAT-RapidArc, with simultaneous integrated boost in 33 fractions for a dose of 69.96 Gy to the high-risk, and of 54.45 Gy to the low-risk volume. RESULTS: Median follow-up was 23 months. In eight cases, locoregional relapse was observed (median time to relapse=10.7 months). Four among eight local recurrences appeared in the high-dose target volume. The 1- and 2-year actuarial disease-free survival rates were 88% and 80%, respectively. The 1- and 2-year actuarial overall survival rates were 94% and 87%, respectively. CONCLUSION: VMAT for oropharyngeal SCC treatment is effective and safe, with interesting rates of control of disease and survival. PMID- 27354608 TI - Impact of Open Laparoscopy in Patients Under Suspicion of Ovarian Cancer. AB - BACKGROUND/AIM: Feasibility and value of diagnostic open laparoscopy (DOL) was assessed in patients presenting under suspicion of advanced ovarian cancer (AOC) mostly with large-volume ascites. PATIENTS AND METHODS: This retrospective study analyzed 143 consecutive patients who underwent DOL for histopathological verification of AOC performed from 2002 to 2012. RESULTS: Out of the 143 patients presenting at our Center with an ovarian mass and mostly with ascites under suspicion of ovarian cancer, we diagnosed 125 AOCs, three AOCs with three concomitant tumors of other origin, and 15 other diseases causing an ovarian mass and ascites mimicking AOC (e.g. gastrointestinal malignancies, tuberculosis, mesothelioma, endometrial cancer and benign conditions). CONCLUSION: DOL can be considered a valid and safe diagnostic tool for histopathologically verifying epithetlial ovarian cancer and preventing patients with other diagnoses undergoing the wrong course of therapy. PMID- 27354609 TI - HIV-related Kaposi's Sarcoma with Musculoskeletal Involvement in the Modern Antiretroviral Era. AB - AIM: To describe the patterns of disease and clinical outcomes of MSK-KS in people living with HIV in the era of (combination anti-retroviral therapy cART). PATIENTS AND METHODS: We reviewed our prospectively collected dataset of patients with HIV with biopsy-proven KS; 17 out of 1,489 seropositive patients were identified with subsequent evidence of MSK involvement by KS. We collected data with regards to clinicopathological parameters and radiological patterns of disease. RESULTS: Fourteen patients (82.4%) had AIDS Clinical Trials Group T1 stage disease at presentation including four (23.5%) with non-nodal visceral disease. At the time of MSK-KS diagnosis, more than 80% of 14 patients had excellent HIV control. The median interval between initial KS to MSK-KS diagnosis was 3.3 years. Five-year overall survival rate from initial KS diagnosis was 76%, and 60% from MSK-KS diagnosis. The majority of patients were asymptomatic and MSK KS involvement was demonstrated during imaging prompted by progression of their mucocutaneous KS. The majority of lesions were lytic with cortical involvement on cross-sectional imaging, whereas a soft-tissue component was commonly associated with long-bone involvement. CONCLUSION: MSK-KS continues to be a rare entity in the modern era of cART, however patients appear to experience significantly improved survival. PMID- 27354610 TI - Prognostic Factors and Treatment Outcome for Patients with Stage IVB Cervical Cancer. AB - AIM: We report a retrospective evaluation for patients with stage IVB cervical cancer in order to identify survival rates and to improve our current practice. PATIENTS AND METHODS: We analyzed 85 patients with stage IVB cervical cancer. For patients appropriate for radical treatment, a combination of external-beam radiotherapy and intracavitary brachytherapy was delivered with/without chemotherapy. Patients with distant metastasis were treated using systemic chemotherapy or palliative radiotherapy. RESULTS: Forty-two patients were treated using radiotherapy alone, 31 using chemotherapy followed by radiotherapy, eight using chemotherapy alone, and four using best supportive care. The 5-year overall survival rate was 9.9%. Multivariate analysis revealed leukocytosis and a poor performance status were independent prognostic factors. Of the 43 patients without these prognostic factors, patients with only lymph node metastasis had a 5-year overall survival rate of 40.5%. CONCLUSION: Radical treatment should be considered in patients who have only lymph rode metastasis and are without leukocytosis and a poor performance status. PMID- 27354611 TI - Prognosis of Patients with Gestational Trophoblastic Neoplasia and Obstetric Outcomes of Those Conceiving After Chemotherapy. AB - AIM: To assess prognosis of gestational trophoblastic neoplasia (GTN) and obstetric outcome after chemotherapy. PATIENTS AND METHODS: Sixty-six patients had diagnosis of hydatiform mole on curettage and 18 developed GTN. Two patients were referred with pathological diagnosis of GTN. Chemotherapy was tailored according to International Federation of Gynecology and Obstetrics risk scoring system. RESULTS: All patients with GTN but one, were recovered by chemotherapy and had no evidence of disease after a median follow-up of 80 months. Only the patient with epithelioid trophoblastic tumor died of disease. Seven out of the eight women who tried to conceive after chemotherapy became pregnant. Ten conceptions occurred, resulting in no molar pregnancy, three miscarriages and seven term-live healthy births (70.0%). All seven babies showed normal development and growth after a median follow-up of 38 months. CONCLUSION: The prognosis of women with GTN is very good, and obstetric outcomes of those who conceive after chemotherapy are similar to those of the general population. PMID- 27354612 TI - Outcome of Resection and Chemotherapy versus Chemotherapy Alone for Retroperitoneal Recurrence of Testicular Cancer Involving the Inferior Vena Cava: A Retrospective Cohort Study of 22 Consecutive Patients. AB - BACKGROUND/AIM: Optimal treatment strategy for retroperitoneal recurrence of testicular cancer involving the inferior vena cava (IVC) is uncertain. The purpose of this study was to validate the hypothesis that surgical resection, en bloc with the involved segment of IVC and its subsequent reconstruction followed by chemotherapy, would yield better oncologic results than chemotherapy alone. PATIENTS AND METHODS: Two consecutive series of patients with retroperitoneal recurrence of testicular cancer involving the IVC, treated with surgical resection plus chemotherapy (group A, n=14) or chemotherapy alone (group B, n=8) were retrospectively reviewed. The mean duration of follow-up was was 65 months (range=8-184). Operative mortality and morbidity in group A, response to chemotherapy in group B, disease-specific survival and quality adjusted life years (QALY) for both groups, were primary end-points of the study. RESULTS: Postoperative mortality and morbidity (group A) were, respectively, nil and 14%. In group B, two patients (25%) fully responded to chemotherapy and remained free from disease progression. Disease-specific survival at 3 and 5 years was 81% and 54% in group A and 36% in group B both at 3 and 5 years, respectively (p=0.02). QALY was 3.92 in group A and 0.77 for both 3 and 5 years in group B, respectively, (p=0.031). CONCLUSION: En bloc resection of retroperitoneal recurrence of testicular tumors invading the IVC, followed by chemotherapy, allows a better survival rate compared to chemotherapy alone. PMID- 27354613 TI - Laparoscopic Liver Resection Is a Feasible Treatment for Patients with Hepatocellular Carcinoma and Portal Hypertension. AB - AIM: To compare outcomes of patients with primary hepatocellular carcinoma (HCC) and portal hypertension (PHT) who underwent laparoscopic liver resection (LLR), open liver resection (OLR) or radiofrequency ablation (RFA). PATIENTS AND METHODS: We retrospectively reviewed 88 patients with primary HCC and PHT who underwent LLR (n=20), OLR (n=48) or RFA (n=20) and analyzed their outcomes by treatment group. To reduce selection bias, covariate distributions in groups were adjusted using inverse probability treatment weighting (IPTW). RESULTS: Five-year recurrence-free survival (RFS) was significantly better in the LLR and OLR than in the RFA group both before and after IPTW adjustment. The OLR group had significantly more postoperative complications than the RFA group; however, there was no significant difference in the postoperative complication rate between LLR and RFA groups. CONCLUSION: LLR may be a feasible treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or advanced hepatocellular carcinoma (A HCC) and PHT. PMID- 27354614 TI - Prognostic Factors Including the Expression of Thyroid Transcription Factor 1 (TTF1) in Patients Irradiated for Limited-disease Small Cell Lung Cancer. AB - AIM: To investigate the impact of tumor-cell expression of thyroid transcription factor 1 (TTF1) on outcomes after irradiation of limited-disease small cell lung cancer (LD-SCLC). PATIENTS AND METHODS: TTF1 expression plus eight factors were evaluated in 32 patients for locoregional recurrence-free survival (LRFS), metastases-free survival (MFS) and overall survival (OS). These factors included age, gender, Karnofsky performance score (KPS), T- and N-category, respiratory insufficiency, smoking during radiotherapy and hemoglobin levels. RESULTS: On univariate analysis of LRFS, no factor achieved significance. Improved MFS was associated with KPS >70 (p=0.029), N0-2 (p=0.003), no respiratory insufficiency (p=0.029) and non-smoking states (p<0.001) on univariate analysis, and N-category (p=0.015) and non-smoking (p<0.001) on multivariate analysis. On univariate analysis, OS was associated with KPS >70 (p<0.001), N0-2 (p=0.002), no respiratory insufficiency (p=0.008) and non-smoking (p=0.022). On multivariate analysis, KPS (p=0.008) and N-category (p=0.018) remained significant. CONCLUSION: In contrast to other factors, TTF1-expression had no significant impact on outcomes after irradiation of LD-SCLC. PMID- 27354615 TI - Assessment of Outcome After Pancreaticoduodenectomy by Junior Surgeons. AB - BACKGROUND/AIM: Pancreaticoduodenectomy (PD) is one of the most complicated procedures. We retrospectively assessed the therapeutic outcome after PD by Junior surgeons. PATIENTS AND METHODS: This study included 253 patients. We retrospectively analyzed surgical outcomes and long-term survivals of PDs performed by Junior surgeons (surgical training year within 10 years) as compared to those by Senior surgeons (surgical training year over 10 years). RESULTS: Operative time was significantly longer in junior surgeons than that in Senior surgeons (p<0.001). Intraoperative blood loss (p=0.079), hospital stay (p=0.803), complications (p=0.700), mortality (p=0.442) were comparable between the two groups. Disease-free and overall survival rates were not statistically different between the two groups in pancreatic cancer (p=0.248 and p=0.526) and in bile duct or ampullary cancer (p=0.873 and p=0.954). CONCLUSION: PD performed by Junior surgeons require approximately 70 more minutes but surgery can be performed safely under appropriate patient selection, intraoperative supervision and perioperative management with comparable long-term survival. PMID- 27354616 TI - Second Primary Malignancies in Hepatocellular Cancer - A US Population-based Study. AB - BACKGROUND/AIM: A second primary malignancy is a serious long-term complication in cancer survivors. The aim of this study was to evaluate the risk of second primary malignancies in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We selected adult patients (>=18 years) diagnosed with HCC from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) 13 database. We calculated the risk of second primary malignancies in these patients using multiple primary standardized incidence ratio (MP-SIR) session of SEER* stat software. Second primary malignancy was defined as a metachronous malignancy diagnosed 6 months or more after an index HCC. RESULTS: A total of 15,296 patients with a diagnosis of primary HCC were reported in the SEER 13 registry during January 1992 to December 2011. A total of 446 (2.83%) developed 466 second primary malignancies with an observed/expected ratio of 10.07 (95% confidence interval=0.97-1.17, p=0.16) and absolute risk of 7.17 per 10,000 population. Risk of stomach and of thyroid cancer were significantly increased among older patients. Risk of lung cancer and of hepatobiliary cancer were significantly higher compared to that of the general population after two years of latency. CONCLUSION: Risk of specific second primary malignancies in adult patients with HCC depends on age of the patient and latency. PMID- 27354617 TI - Hepatic Arterial Infusion of Polyethylene Glycol Drug-eluting Beads for Primary and Metastatic Liver Cancer Therapy. AB - BACKGROUND/AIM: Recently, there has been the launch of the new Polyethylene glycol (PEG) drug-eluting beads (LifePearl(r)) for transarterial chemoembolization. Their innovation is that PEG guarantees more compressibility, elasticity and maximizes beads' suspension time. We applied these beads for hepatic intra-arterial infusion of irinotecan or doxorubicin for the therapy of primary and metastatic liver cancer. PATIENTS AND METHODS: We treated 20 consecutive patients, affected by unresectable primary liver cancer (PLC) or hepatic metastases (refractory to chemotherapy) using chemoembolization with doxorubicin or irinotecan pre-loaded Lifepearls. RESULTS: Tumor response rate was >80% in most patients with 63% of complete and 37% of partial response. We observed no complications during the chemoembolization and no severe general drug related side-effects. CONCLUSION: Our data suggest that chemoembolization with LifePearl(r) is efficacious and safe for the treatment of liver cancer as indicated by good tolerability, quality of life and high tumor response. PMID- 27354618 TI - Comparison of Outcome of Hepatic Arterial Infusion Chemotherapy and Sorafenib in Patients with Hepatocellular Carcinoma Refractory to Transcatheter Arterial Chemoembolization. AB - AIM: To compare the outcome of 5-fluorouracil (FU)-based hepatic arterial infusion chemotherapy (HAIC) with sorafenib monotherapy in patients with hepatocellular carcinoma (HCC) refractory to transcatheter arterial chemoembolization (TACE). PATIENTS AND METHODS: In this retrospective cohort study, 123 patients with HCC refractory to TACE, with Child-Pugh A and free of extrahepatic metastasis, were divided into two groups: 65 received HAIC and 58 received sorafenib. Since the size of main tumor and portal vein invasion were significantly different between the HAIC and sorafenib groups, we selected 48 patients from the 65 patients of the HAIC group and 48 from the 58 patients of the sorafenib group. The model used one-to-one matching between the two groups using the case-control method matching method. The clinical characteristics of patients of the case-control HAIC (n=48) and sorafenib groups (n=48) were similar. Overall survival, time to progression and time to treatment failure (TTTF) were compared between the two groups. RESULTS: The median survival time and TTTF were significantly longer in the sorafenib group than in the HAIC group (15 and 12.2 months versus 8 and 4.4 months, respectively; p=0.021 and p=0.002, respectively). Multivariate analysis identified male gender (p=0.008), relative tumor size <50% (p=0.012), alpha-fetoprotein <400 ng/ml (p=0.005), and treatment with sorafenib (p=0.001) as significant and independent determinants of better overall survival. CONCLUSION: In patients with HCC refractory to TACE, overall survival was favorable in those treated with sorafenib rather than HAIC. PMID- 27354619 TI - Comparison of Panitumumab Plus Irinotecan and Cetuximab Plus Irinotecan for KRAS Wild-type Metastatic Colorectal Cancer. AB - BACKGROUND/AIM: Panitumumab and cetuximab are known to be effective treatments for KRAS wild-type metastatic colorectal cancer (mCRC). However, it remains unclear which of these two biologic agents confers the greatest benefit when combined with irinotecan in patients with KRAS wild-type mCRC previously treated with fluoropyrimidine, oxaliplatin and irinotecan. PATIENTS AND METHODS: Data, from 139 patients who received panitumumab or cetuximab, in combination with irinotecan, for KRAS wild-type mCRC previously treated with fluoropyrimidine, oxaliplatin and irinotecan were analyzed. The efficacy and safety of panitumumab plus irinotecan was compared to that of cetuximab plus irinotecan. RESULTS: Baseline characteristics of the panitumumab plus irinotecan (n=42) and cetuximab plus irinotecan (n=97) groups were similar. Among patients with measurable lesions, the response rate was 34% in the panitumumab plus irinotecan group and 20% in the cetuximab plus irinotecan group. Median progression-free survival (PFS) was 4.3 and 5.7 months in the panitumumab and cetuximab groups, respectively. Median overall survival was 13.6 months with panitumumab and 11.2 months with cetuximab. CONCLUSION: Panitumumab plus irinotecan was well-tolerated and displayed a similar level of efficacy to that of cetuximab plus irinotecan. PMID- 27354620 TI - HER2 Equivocal Status in Early Breast Cancer Is Not Associated with Higher Risk of Recurrence. AB - AIM: The primary aim of the study was to assess the association between risk of recurrence and HER2 equivocal gene status through immunohistochemistry in patients with early breast cancer. PATIENTS AND METHODS: We retrospectively analyzed clinical and pathological data of 455 consecutive patients with early breast cancer (BC) who were HER2(+) and had a HER2/CEP17 ratio <2.0, who underwent surgery at the European Institute of Oncology after 2007. The role of HER2/CEP17 ratio on recurrence-free survival was assessed with univariate and multivariate Cox regression models. RESULTS: We found no significant association between risk of recurrence and HER2 equivocal testing in patients with early breast cancer. In subgroup analysis, a significant interaction between HER2/CEP17 ratio and nodal involvement was observed (p=0.02). CONCLUSION: Patients with HER2 equivocal status have no significantly higher risk of recurrence. PMID- 27354621 TI - Prognostic Value of Severe Lymphopenia During Pelvic Concurrent Chemoradiotherapy in Cervical Cancer. AB - AIM: To investigate whether common terminology criteria for adverse events (CTCAE) grade 4 lymphopenia (<200 cells/MUl) during concurrent chemoradiotherapy (CCRT) is relevant to poor survival. PATIENTS AND METHODS: We analyzed 124 patients with newly diagnosed Federation of Gynecology and Obstetrics (FIGO) stage I-III cervical cancer who received weekly cisplatin-based CCRT and brachytherapy using Kaplan-Meier curves and the Cox proportional hazard models. RESULTS: Grade 4 lymphopenia significantly predicted disease-specific survival (DSS) and progression-free survival (PFS) (adjusted hazard ratio (95% confidence interval (CI))=3.6 (1.37-9.44), p=0.009 and 3.28 (1.27-8.48), p=0.014, respectively). The 5-year DSS and 3-year PFS were significantly higher among patients with grade 2-3 lymphopenia (>=200 cells/MUl) than among those with grade 4 lymphopenia (84.8% vs. 50.4%, p<0.001, and 80.7% vs. 50%, p=0.002, respectively). CONCLUSION: Severe lymphopenia during CCRT could predict poor survival. PMID- 27354622 TI - Nodal Ratio as a Prognostic Factor in Patients with Four or More Positive Axillary Nodes Treated with Breast-conserving Therapy and Regional Nodal Irradiation. AB - AIM: This study aimed to investigate the prognostic value of the axillary lymph node ratio (i.e. positive axillary nodes to nodes removed) in patients with breast cancer treated with conservative surgery and regional radiotherapy. PATIENTS AND METHODS: We retrieved the records of 195 patients with breast cancer with pathological stage pT1-2 pN2-3, treated from January 2005 to December 2013 at our Radiation Oncology Centers; their clinical data were retrospectively evaluated. All patients underwent lumpectomy or quadrantectomy with axillary lymph node dissection, adjuvant chemo-with/without hormonal therapy and irradiation to the whole breast and ipsilateral axillary apex, infraclavicular and supraclvicular nodes, excluding internal mammary nodes. The primary end-point was to evaluate the nodal ratio as a prognostic factor; moreover, the following prognostic factors were evaluated: age, biological status and molecular profile. RESULTS: The median follow-up was 58 months (range=32-117.6 months). Two- and 5 year overall and recurrence-free survival rates were 96% and 88%, and 92% and 85%, respectively. On univariate analysis, factors influencing overall survival were nodal ratio >0.65 (p=0.033) and age (p=0.023); time to recurrence was detrimentally impacted only by Ki67 positivity >=50% (p=0.049). At multivariate analysis, no significant associations were found. CONCLUSION: Adding irradiation to regional nodes after conservative surgery in patients with breast cancer with more than three positive axillary nodes does not alter the prognostic value of the nodal ratio, and we confirm this to be an important factor for predicting overall survival. PMID- 27354623 TI - Pilot Study of Intrahepatic Artery Chemotherapy in Combination with Sorafenib in Hepatocellular Carcinoma. AB - BACKGROUND/AIM: Sorafenib and chemoembolization of the liver (TACE) have both produced increased survival in hepatocellular carcinoma (HCC). Some patients cannot tolerate TACE due to portal vein thrombosis or risk of liver failure. In this pilot trial, we aimed to combine intrahepatic infusion (IA) of cisplatin or carboplatin with sorafenib for unresectable HCC. PATIENTS AND METHODS: Patients with Child's A or early B received IA cisplatin or carboplatin every 6 weeks with oral sorafenib. MRI/CT scans were performed every 6 weeks. RESULTS: Eleven patients were accrued. Of 10 evaluable patients, 6 had clinical benefit (4 partial responses for 2+, 3+, 8+ and 18 months, 2 minor responses). Two patients were down-staged enough for ablation therapy or liver transplant and remain free of disease for 32+ and 36+ months. Toxicity was generally tolerable. CONCLUSION: Preliminary results are encouraging and this combination may down-stage some patients with unresectable disease. PMID- 27354624 TI - Biomimetic Peptides for the Treatment of Cancer. AB - Cancer remains one of the leading causes of death worldwide, indicating that current cancer therapies are ineffective. Therefore, new treatments with high specificity and low toxicity are needed. Cancerous cells can be distinguished from normal cells based on expression of key proteins, namely surface proteins, scaffold proteins and signaling molecules. Moreover, cancer cells communicate with the tumor microenvironment consisting of a heterogenous population of cells, extracellular matrix components and soluble factors such as cytokines/chemokines and growth factors. Most therapeutic interventions have been designed to specifically target these proteins of interest. Biomimetic peptides (BPs) are artificially designed peptides that imitate the action of parent proteins or peptides. BPs can be classified into at least three types based on their target molecule: BPs that target (i) cell-surface molecules, (ii) intracellular molecules, and (iii) cancer cell-tumor microenvironment interactions. In this review, we analyze/discuss the current strategies for targeting tumors using BPs. PMID- 27354625 TI - MET Expressed in Glioma Stem Cells Is a Potent Therapeutic Target for Glioblastoma Multiforme. AB - BACKGROUND: Glioblastoma multiforme (GBM) is the most frequent and the most malignant tumor among adult brain tumors. Previous reports led us to hypothesize that the proto-oncogene mesenchymal-epithelial transition (MET) expressed in glioma stem cell-like cells (GSCs) would be a potent therapeutic target for GBM. PATIENTS AND METHODS: To address this question, we analyzed 113 original samples of tumors from patients based on immunohistochemistry. During this process, we were able to establish GSC lines from patients with GBM that were MET-positive and MET-negative. Using these cells, we tested the therapeutic impact of a MET inhibitor, crizotinib, both in vitro and in vivo. RESULTS: Patients with MET positive GBM exhibited poor survival. GSC-based experiments revealed that treatment with crizotinib, both in vitro and in vivo, exhibited therapeutic efficacy particularly against MET-positive GSCs. CONCLUSION: Based on these findings, we conclude that MET expressed in GSCs might be a potent therapeutic target for GBM. PMID- 27354626 TI - Flow Cytometric Analysis of Ovarian Cancer Ascites: Response of Mesothelial Cells and Macrophages to Cancer. AB - AIM: To evaluate the response of mesothelial cells and macrophages in the peritoneal fluid of epithelial ovarian malignant tumors using flow cytometry immunophenotyping. MATERIALS AND METHODS: Thirteen peritoneal fluid samples collected from surgery or scentesis of epithelial ovarian malignant tumor patients were assayed using flow cytometry. Cytological and pathological diagnosis was performed on the same ascites and resected tumor specimens. Samples were treated with antibodies against established markers of mesothelial cells (podoplanin), macrophages (CD14) and the hyaluronan receptor (CD44). RESULTS: A significant association was observed between the results of cytology and expression of podoplanin, CD44 and CD14 (p<0.05) in peritoneal macrophages. No significant association was observed between the results of cytology and expression of podoplanin, CD44 and CD14 in mesothelial cells in ascites. CONCLUSION: Expression of surface molecules, such as podoplanin, CD44 and CD14 was increased in the peritoneal macrophages of epithelial ovarian cancer patients, suggesting that the cell-cell or cell-matrix interaction was enhanced during cancer dissemination in the peritoneum. Analysis of the peritoneal fluid using flow cytometry immunophenotyping may be useful for evaluating the diagnosis and pathophysiology of ovarian cancer dissemination. PMID- 27354627 TI - Resveratrol Overcomes Cellular Resistance to Vemurafenib Through Dephosphorylation of AKT in BRAF-mutated Melanoma Cells. AB - BACKGROUND/AIM: The serine/threonine-protein kinase B-Raf (BRAF) V600E mutant (BRAF(V600E)) inhibitor vemurafenib, has improved clinical outcomes for patients with BRAF(V600E) melanoma, but acquired cellular resistance mediated by AKT serine/threonine kinase 1 (AKT) phosphorylation limits its efficacy. We examined the effect of resveratrol on vemurafenib-resistant melanoma cells. MATERIALS AND METHODS: A vemurafenib-resistant human metastatic melanoma cell line positive for the BRAF V600E mutation was established. The anti-tumorigenic effects of vemurafenib and resveratrol, both alone and in combination, were examined through analysis of cell proliferation and protein expression. RESULTS: The level of phosphorylated AKT (p-AKT) was increased in the primary melanoma cells after treatment with vemurafenib, and the basal level of p-AKT was increased in vemurafenib-resistant melanoma cells. Notably, resveratrol both alone and in combination with vemurafenib effectively suppressed cell proliferation and AKT phosphorylation in both parental and vemurafenib-resistant melanoma cells. CONCLUSION: Vemurafenib resistance can be reversed by addition of resveratrol in patients undergoing treatment with BRAF inhibitors. PMID- 27354628 TI - The Organo- and Cytoprotective Effects of Heat-shock Protein in Response to Injury Due to Radiofrequency Ablation in Rat Liver. AB - AIM: In treating liver tumors, preserving hepatic reserve and reducing surgical invasiveness are important for minimizing postoperative complications. Geranylgeranylacetone (GGA) is reported to selectively induce heat-shock protein 70 (HSP70), which initiates a powerful cytoprotective effect. We investigated the function of HSP70 under conditions of radiofrequency ablation (RFA) of the liver. MATERIALS AND METHODS: Male Wistar rats were divided into three groups: a control group, a group administered GGA, and a group administered GGA plus quercetin, an HSP70 synthesis inhibitor. Expression of HSP70 and heat-shock factor-1 (HSF1) in the liver was measured at the protein level, and severity of liver damage was investigated using serum and hepatic tissue. RESULTS: The GGA-treated group had higher expression of HSP70 and HSF1 than the other groups. Peak liver damage in all groups occurred 6 h after RFA. The GGA-treated group also had significantly less liver damage and lower serum level of the inflammatory cytokine tumor necrosis factor-alpha, and a lower rate of apoptosis in tissue around post ablation necrosis. Expression of HSP70 and HSF1 was suppressed in the group treated with GGA and quercetin, and this group had severe liver damage. CONCLUSION: Induction of HSP in the liver by GGA may be applicable in future treatments for hepatocellular carcinoma or liver metastasis. The present findings suggest that if preoperative administration of GGA can offer protective effects in the liver, treatment options could be increased and liver failure and other complications might be avoided. PMID- 27354629 TI - Dewaxed Brown Rice Contains a Significant Amount of Lipopolysaccharide Pointing to Macrophage Activation via TLRs. AB - BACKGROUND/AIM: Oral ingestion of lipopolysaccharide (LPS) has been shown to be effective in diseases' prevention. Brown rice contains large amounts of LPS not actively consumed because of bad taste. Recently, a new type of brown rice with its wax layer removed has been produced. In this report, we measured the LPS content of this dewaxed rice and evaluated the function of innate immune activation on macrophages. MATERIALS AND METHODS: Dewaxed brown rice and polished rice were prepared using the Saika-style rice polishing process. LPS content extracted using hot water from this sample was evaluated by the Limulus reaction and the activation of macrophage RAW246.7 cells was evaluated by nitric oxide (NO) production. In addition, toll-like receptors (TLRs) 2-, 4- and 9-induced human embryonic kidney (HEK) 293 cells were used for the confirmation of the activated pathway. RESULTS: Mean LPS content in the 15 types of dewaxed brown rice was found to be 6.4+/-2.6 MUg/g, while that of brown rice was 10.9+/-4.3 MUg/g. The extract of dewaxed brown rice induced significant amounts of NO by RAW246.7 cells, while production was reduced to 1/6 by adding polymyxin B. The macrophage activating effect of dewaxed brown rice was 79- and 51-times higher than that of polished rice in TLR4- and 2-induced HEK 293 cells. CONCLUSION: LPS content in dewaxed brown rice was found to be able to activate macrophages. This rice activated macrophages mainly via the TLR4 and, to a lesser extent, TLR2 pathways. It is suggested that dewaxed brown rice can be considered effective in allergy and cancer prevention. PMID- 27354630 TI - 5-Aminolevulinic Acid Enhances Ultrasound-mediated Antitumor Activity via Mitochondrial Oxidative Damage in Breast Cancer. AB - BACKGROUND/AIM: 5-Aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX), is now used for photodynamic therapy (PDT) of pre-cancers of the skin and photodynamic diagnosis (PDD) of brain tumors. Sonodynamic therapy (SDT) of cancers with ultrasound has been studied using 5-ALA as a sonosensitizer. In this article, we evaluated the sonosensitizing activity and mode of action of 5 ALA/PpIX by using mouse mammary tumor EMT6 cells. RESULTS: 5-ALA-SDT showed significant antitumor effects toward EMT6 cells in vitro and in vivo. The fluorescence of MitoSOX Red, an indicator specific for mitochondrial superoxide, was significantly increased by 5-ALA-SDT. Moreover, the fluorescence derived from JC-1, an indicator of mitochondrial membrane potential, was also significantly increased by 5-ALA-SDT. These findings suggest that mitochondria are one of the target organelles of 5-ALA-SDT. PpIX enhanced reactive oxygen species (ROS) production from tert-butyl hydroperoxide (tBHP), suggesting that PpIX might stabilize or promote ROS generation from tBHP. CONCLUSION: 5-ALA-SDT showed an antitumor effect in mouse mammary tumor EMT6 cells through oxidation of the mitochondrial membrane via ROS production. PMID- 27354631 TI - Development of an Evaluation Device for Phagocytic Activity of New Phagocytes Using Simple and pH-sensitive Particles that Do Not Require Pre-treatment. AB - BACKGROUND/AIM: Phagocytic activity is affected by a number of different stress and age-dependent factors. An easy measurement of phagocytic activity is thought to allow an indicator of an individual's health. In this study, we investigated conditions of measurement to easily evaluate the activity of phagocytosis of phagocytic cells (macrophages and neutrophils) using an easy-to-use prototype, which was improved from the device by Hamamatsu Photonics K.K., to detect neutrophil activity using subtle fluorescence. MATERIALS AND METHODS: pH sensitive fluorescent particles (pHrodo-Green E. coli Bio particles, GE particles) were added to mouse-derived macrophage cell lines (J774.1) and then incubated for 2 h at 37 degrees C. For negative control, the phagocytosis inhibitor cytochalasin D (CyD), was added prior to culture. Next, fluorescence intensity was measured by the Prototype to evaluate the phagocytic activity of macrophages and neutrophils. Phagocytosis was also confirmed by flow cytometry. RESULTS: The Prototype detected a steady fluorescence increase in 5 sec in J774.1 after phagocytosis, using GE particles as a negative control in the presence of CyD. Furthermore, detection was possible at 10(4) cells/test, a concentration where the flow cytometer had difficulty for detection. CONCLUSION: The Prototype enables measurement of the phagocytic activity within a short period of time, even with a small sample amount, thus establishing the basic conditions of measurements of phagocytosis. PMID- 27354632 TI - Macrophages Exhibit a Large Repertoire of Activation States via Multiple Mechanisms of Macrophage-activating Factors. AB - BACKGROUND/AIM: Macrophages are important components of human defense systems and consequently key to antitumor immunity. Human-serum macrophage activation factor (serum MAF) can activate macrophages, making it a promising reagent for anticancer therapy. MATERIALS AND METHODS: We established four different macrophage subtypes through introduction of different culture conditions to THP-1 and U937-derived macrophages. We assessed phagocytic activity to understand subtype responses to typical macrophage activation factors (MAFs) and the activation mechanisms of serum MAF. RESULTS: All four macrophage subtypes differed in their response to all MAFs. Moreover, serum MAF had two different activation mechanisms: N-acetylgalactosamine (GalNAc)-dependent and GalNAc independent. CONCLUSION: Macrophage activation states and mechanisms are heterogeneous. PMID- 27354633 TI - DBA Lectin Binds to Highly Proliferative Mouse Erythroleukemia Cells. AB - BACKGROUND/AIM: Hematopoietic malignancies lead to disease states involving abnormal proliferation of blood cells. Ki-67 and carboxyfluorescein succinimidyl ester (CFSE) are assays used to examine the proliferation status of cells but affect cell viability. In this study, we used lectins to bind to surfaces of proliferating cells with different phenotypes while preserving cell viability. MATERIALS AND METHODS: The mouse lymphocyte Friend leukemia F5-5.F1 cell line was stained using biotin-conjugated lectins from Canavalia ensiformis (ConA), Dolichos biflorus (DBA), Erythrina cristagalli (ECA), Lens culinaris (LCA), Phaseolus vulgaris (PHA-E4), Arachis hypogaea (PNA), Ulex europaeus (UEA) and Triticum vulgaris (WGA) and sorted by fluorescence-activated cell sorting. Morphology, gene expression and proliferation assays were performed on sorted cells. RESULTS: DBA, LCA and PHA-E4 probing sorted cells based on surface phenotype. Gene expression analysis showed that myelocytomatosis oncogene (Myc), cyclin D1 (Ccnd1), and cyclinD2 (Ccnd2) were more highly expressed in the DBA(High) fraction than DBA(Int) and DBA(Neg) fractions. Ki-67 expression and MTS assay correlated with the DBA-binding pattern, with DBA(High) reflecting the highest proliferative tendency. CONCLUSION: Labeling with DBA allows selection of proliferating cells using flow cytometry. PMID- 27354634 TI - Aryl Hydrocarbon Receptor Antagonist StemRegenin 1 Promotes the Expansion of Human Promyelocytic Leukemia Cell Line, NB4. AB - BACKGROUND/AIM: StemRegenin 1 (SR1), an antagonist of aryl hydrocarbon receptor (AHR), reportedly promotes expansion of hematopoietic stem cells but its effect on leukemia cells is unclear. This study focused on the role of SR1 in leukemia cell proliferation. MATERIALS AND METHODS: AHR expression was compared in the cell lines Jurkat, Kasumi-1, NB4 and K562, using real-time polymerase chain reaction. Highly AHR-expressing NB4 cells were cultured with SR1 for 2 and 4 days, and evaluated for viability and gene expression. DNA microarray was also performed. RESULTS: The viability of NB4 cells treated with 1.5 MUM SR1 increased at day 4. Expression of B-cell CLL/lymphoma 2 (BCL2) was up-regulated, while that of BCL2 associated X protein (BAX) was down-regulated at day 2. Increased cyclin D1 (CCND1), CCND2 and v-myc avian myelocytomatosis viral oncogene homolog (MYC) expressions were observed at day 4. Global gene expression profiles showed up regulation of splice variant-related genes and down-regulation of inflammation related genes. CONCLUSION: SR1 promotes the expansion of NB4 cells in vitro, implying the need for caution regarding in vivo use of R1. PMID- 27354635 TI - An Antitumor 2-Hydroxyarylidene-4-cyclopentene-1,3-Dione as a Protein Tyrosine Kinase Inhibitor: Interaction Between TX-1123 Derivatives and Src Kinase. AB - BACKGROUND: Protein tyrosine kinases (PTKs) play major roles in signal transduction during cell proliferation and apoptosis. Tyrphostin AG17 was previously shown to be a potent tumor growth inhibitor, while AG17 induced apoptosis and inhibited activity of cyclin-dependent kinase 2. We herein describe the binding features of tyrphostin AG17 analogs, such as TX-1123, with Src kinase (Src-K). MATERIALS AND METHODS: Structural data for Src-K were obtained from a protein data bank (ID=2SRC), and the molecular interactions between Src-K and TX 1123 derivatives were examined. RESULTS: TX-1123 exihibited potent Src-K inhibitory activity (half maximal-inhibitory concentration=2.2 MUM), and fit into the pocket of the Src-K molecule as well as c-AMP did. CONCLUSION: The binding profiles of TX-1123 derivatives differed from each other, while their Src-K inhibitory activities were affected by their fit in the Src-K molecule. PMID- 27354636 TI - Anti-tumor Effect of Intravenous Administration of CRM197 for Triple-negative Breast Cancer Therapy. AB - BACKGROUND/AIM: Heparin-binding epidermal growth factor-like growth factor (HB EGF), which belongs to the epidermal growth factor family, is a rational therapeutic target for triple-negative breast cancer (TNBC). This study aimed to assess the anti-tumor efficacy of intravenous (i.v.) HB-EGF-specific inhibitor (CRM197) for TNBC. MATERIALS AND METHODS: NOD/SCID mice were subcutaneously injected withTNBC cells, MDA-MB-231, and, then, treated with i.v. CRM197 in either dose- or frequency-dependent manners, using an advanced cancer model and an adjuvant therapy model. Tumor volume and mouse body weight were calculated weekly. Statistical significance was assessed by the Mann-Whitney U-test. RESULTS: Mice that received i.v. CRM197 showed a significant anti-tumor effect in dose- and frequency-dependent manners in both models. However, their body weight did not differ significantly among groups. CONCLUSION: These results suggest that i.v. CRM197 is an effective treatment for TNBC. PMID- 27354637 TI - Host CD40 Is Essential for DCG Treatment Against Metastatic Lung Cancer. AB - BACKGROUND/AIM: For the application of invariant natural killer T (iNKT) cells in cancer therapy, the CD40-CD40L interaction is indispensable in administering alpha-galactosylceramide (alphaGalCer). We hypothesized that CD40 plays an important role in dendritic cells (DC) pulsed with alphaGalCer (DCGs) in the treatment of lung metastases. MATERIALS AND METHODS: Wild-type (WT) and CD40(-/-) mice were treated with DCGs isolated from WT or CD40(-/-) mice in a B16F10 lung metastases model and NK and NKT cell activity in lungs and the spleen were examined. RESULTS: DCG treatment improved WT mice survival but CD40(-/-) hosts received no survival benefit. Conversely, attenuation of a therapeutic effect in mice treated with CD40(-/-) DCGs was not observed. The functional activities of NK and NKT cells in DCG-treated CD40(-/-) mice were partially suppressed. CONCLUSION: Host CD40 is essential for DCG treatment to have a therapeutic effect on B16F10 lung metastases. PMID- 27354638 TI - Liver Injury After Invariant NKT Cell Activation by Free Alpha-galactosylceramide and Alpha-galactosylceramide-loaded Dendritic Cells. AB - BACKGROUND/AIM: Both free alpha-galactosylceramide (alphaGalCer) and alphaGalCer loaded dendritic cells (DCG) activate invariant natural killer T (iNKT) cells to varying degrees, with alphaGalCer inducing liver injury. We sought to evaluate liver injury by these two pathways. MATERIALS AND METHODS: Mice were injected with alphaGalCer or DCG followed by analysis of serum alanine transaminase (ALT) activity levels, mortality and liver function. RESULTS: While ALT levels were elevated after DCG in a tumor necrosis factor (TNF)-alpha-dependent manner, DCG did not cause lethal injury. More serious injury of liver CD31-positive endothelial cells (CD31(+) EC) was observed in mice treated with alphaGalCer than with DCG. Furthermore, liver CD31(+) EC of alphaGalCer-treated mice induced naive liver lymphocytes to produce TNF-alpha. CONCLUSION: DCG treatment did not induce lethal liver injury. CD31(+) EC may play an antigen-presenting role to iNKT cells after alphaGalCer treatment and may be a cause of lethal injury. PMID- 27354639 TI - Screening for Identification of Personalized Food to Promote Adiponectin Secretion in Patients with Cancer. AB - BACKGROUND/AIM: Adiponectin is secreted specifically from adipose tissue. Low serum adiponectin levels may cause metabolic syndrome, which is also a risk factor for carcinogenesis. Several studies have suggested a negative correlation between adiponectin and risk of cancers. This study examined the adiponectin secretion-promoting effect of food ingredients in adipose-derived stem cells (ADSCs) obtained from patients with cancer. PATIENTS AND METHODS: ADSCs from 7 lifestyle disease cancer patients were differentiated into adipocytes. Subsequently, the adipocytes were treated with 49 food constituents. The adiponectin levels in cell culture supernatants were measured after 48 and 96 h. RESULTS: Soy genistein extract, lychee low-molecular-weight polyphenol, olive extract and turmeric promoted adiponectin secretion. CONCLUSION: Food constituents that promoted adiponectin secretion were identified using ADSCs derived from patients. This study suggested the possibility of a new treatment approach to prevent cancer recurrence. PMID- 27354640 TI - Effect of Xenotransplantation Site on MicroRNA Expression of Human Colon Cancer Stem Cells. AB - BACKGROUND: Cancer stem cells (CSCs) have a high tumorigenic ability to form patient-derived tumor xenografts (PDXs). PDXs are an attractive pre-clinical model, but gene expression and biological behavior of cancer cells in the tumor will change during establishment and passage of PDXs. MATERIALS AND METHODS: Human colon cancer PDX was established and passaged either subcutaneously or orthotopically into the murine intestine. Histology and flow cytometric profile of the surgical specimen and the PDX were analyzed. CSCs were then isolated from the tumors and their microRNA (miRNA) expression was analyzed by semi quantitative polymerase chain reaction. RESULTS: The surgical specimens and PDXs were histologically similar. The size of CSC population increased and expression of miRNAs in CSCs changed in the passaged PDXs. Expression of oncogenic miRNAs was highly up-regulated in the CSCs of the orthotopically passaged PDXs. CONCLUSION: The xenotransplantation site and the number of tumor passages affect the miRNA expression of human colon CSCs. PMID- 27354641 TI - Immunopotentiator from Pantoea agglomerans 1 (IP-PA1) Promotes Murine Hair Growth and Human Dermal Papilla Cell Gene Expression. AB - BACKGROUND/AIM: The lipopolysaccharide (LPS)-like compound derived from Pantoea agglomerans (immunopotentiator from Pantoea agglomerans 1 (IP-PA1)) has been used not only as dietary supplement or cosmetic for humans, but also by Japanese veterinarians as an anti-tumor, anti-allergy, "keep a fine coat of fur" and hair growth-promoting functional food for dogs and cats. In the present study, we focused on the hair growth-promoting effects of IP-PA1 on a hair-shaved animal model and its mechanism of action. We also investigated its potential on gene expression after stimulating human dermal papilla cells with IP-PA1. MATERIALS AND METHODS: The hair on the back of a C3H/HeN mouse was shaved and IP-PA1 was orally administered or applied to the skin. The status of hair growth was observed and recorded for 14 days. Skin was collected and histological tissue examination was performed with respect to hair growth status using hematoxylin and eosin staining. After IP-PA1 administration (2 and 10 MUg/ml) to human dermal papilla cell culture system for 24 h, fibroblast growth factor-7 (FGF-7) and vascular endothelial growth factor (VEGF) mRNA expression were measured using real-time polymerase chain reaction (PCR) analysis. RESULTS: IP-PA1, when given orally, showed a tendency to promote hair growth in mice. In addition, skin application also significantly promoted hair growth, while histopathological examinations further demonstrated hair elongation from dermal papilla cells. In the human dermal papilla cell culture system, significant FGF-7 and VEGF mRNA expressions were observed (p<0.05). CONCLUSION: An underlying mechanism of gene expression by which IP-PA1 promotes hair growth was suggested to be different from that of medicine and traditional hair tonics, such as minoxidil and adenosine. PMID- 27354642 TI - Effect of Lipopolysaccharide Derived from Pantoea agglomerans on the Phagocytic Activity of Amyloid beta by Primary Murine Microglial Cells. AB - BACKGROUND/AIM: Monophosphoryl lipid A, lipopolysaccharide (LPS)-derived Toll like receptor (TLR) 4 agonist, has been shown to be effective in the prevention of Alzheimer's disease (AD) by enhancing phagocytosis of amyloid beta (Abeta) by brain microglia. Our recent study demonstrated that oral administration of LPS derived from Pantoea agglomerans (LPSp) activates peritoneal macrophages and enhances the phagocytic activity via TLR4 signaling pathway; however, the effect of LPSp on Abeta phagocytosis in microglia is still unknown. MATERIALS AND METHODS: Primary microglial cells were isolated from adult mouse brain by enzymatic digestion, following myelin removal and magnetic separation of cluster of differentiation (CD) 11b. Phagocytic analysis of the primary microglia was measured by using HiLyteTM Fluor 488-conjugated Abeta1-42 RESULTS: Using our protocols, the average yield of isolated CD11b(+) cells was around 2.2*10(5) cells per brain. CD11b(+)CD45(+)CD39(+) cells were defined here as microglia. The phagocytic activity of Abeta1-42 by the isolated microglia was confirmed. LPSp (10 ng/ml) pre-treatment for 18 h significantly increased Abeta phagocytic activity. CONCLUSION: The enhancement of Abeta1-42 phagocytosis by LPSp treatment in the primary mouse microglia was demonstrated for the first time. PMID- 27354643 TI - Gene Expression in Lipopolysaccharide-treated Human Monocytes Following Interaction with Hepatic Cancer Cells. AB - BACKGROUND/AIM: Monocytes migrate into the tissue where they differentiate into various types of macrophages with tissue-specific characteristics. When human monocytes are co-cultured with colon cancer cells they exhibit increased mRNA expression of angiogenesis- and signaling pathway-related genes; however, this increase is suppressed by pretreatment with low-dose lipopolysaccharide (LPS). Thus, LPS-treated human monocytes may be useful in suppressing tumor invasion and proliferation in colon cancer. However, it is suggested that the characteristics of tumor-associated macrophages may differ depending on the type of cancer. The function of human tumor-associated macrophages in hepatic cancer remains unclear. In this study, we investigated mRNA expression of various genes in LPS-treated human monocytes following interaction with hepatic cancer cells. MATERIALS AND METHODS: The human monocyte cell line THP-1 was treated with LPS and subsequently co-cultured with the human hepatic cancer cell line HepG2. mRNA expression of various factors were then analyzed using quantitative real-time polymerase chain reaction (PCR) and DNA microarray. RESULTS: The mRNA expressions of monocyte chemotactic protein-1, vascular endothelial growth factor-A, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-8, nuclear factor-kappaB, RelB, signal transducer and activator of transcription 3, IL-10 and transforming growth factor beta in THP-1 cells following interaction with HepG2 cells, were suppressed by pretreatment with LPS. CONCLUSION: LPS-treated human monocytes may be useful in suppressing tumor invasion and proliferation of hepatic cancer, as well as colon cancer. The co-culture system of monocytes and cancer cells may be beneficial for evaluating antitumor effects in LPS-treated monocytes. PMID- 27354644 TI - Global Liver Gene Expression Analysis on a Murine Metabolic Syndrome Model Treated by Low-molecular-weight Lychee Fruit Polyphenol (Oligonol(r)). AB - BACKGROUND/AIM: Oligonol(r) (OLG) is a low-molecular-weight lychee fruit polyphenol mainly containing catechin-type monomers and oligomers of proanthocyanidins. Dietary OLG supplementation reportedly improves lipid metabolism disorder and lowers the visceral fat level in animal and human studies. Thus, we investigated the mechanism behind the protective and beneficial effects of OLG on a Western diet (WD)-induced metabolic syndrome (MetS) of a murine model. MATERIALS AND METHODS: Using the C57BL/6J mouse for the MetS model, mice were divided into three groups: control (normal diet: ND), Western diet (WD) and WD + 0.5% OLG (OLG) groups. The WD group was fed a high-calorie (high fructose plus high fat) diet for 12 weeks to develop MetS. At week 12, all mice were sacrificed and the blood and liver were obtained for histological and biological examinations and RNA sequencing (RNA-Seq). RESULTS: Body weight, liver weight, plasma triglycerides (TG), total cholesterol (T-Cho) and alanine aminotransferase (ATS) levels of both OLG groups were significantly lower than those of the WD group. On histological examination of the liver, the area of fatty deposits was shown to be suppressed by OLG administration. Expression gene analysis in the liver of WD- versus OLG-fed mice by RNA-Seq showed that 464/45,706 genes exhibited a significant change of expression (corrected p-value <0.05, absolute value of fold change (FC) >=2). Gene network analysis showed that genes related to hepatic steatosis, liver inflammation and tumor invasion were inactivated in the OLG group. In particular, the lipid metabolism-related genes Lpin1, Adig and Cidea were regulated by OLG administration. CONCLUSION: OLG may function to suppress MetS and the progression of geriatric diseases in WD-fed mice by regulating the expression of lipid metabolism, inflammation and tumor related genes in the liver. PMID- 27354645 TI - Immunohistochemical Analysis of WT1 Antigen Expression in Various Solid Cancer Cells. AB - For a peptide-pulsed dendritic cell (DC) vaccine to work effectively in cancer treatment, it is significant that the target protein is expressed in cancer cells. Wilms' tumor 1 (WT1) has been identified as a molecular target for immune cell therapy of cancer. We evaluated the protein expression levels of WT1 in various solid tumors, as well as mucin 1 (MUC1) or major histocompatibility complex (MHC) class l molecules. Seven hundred and thirty-eight patients whose tissue samples were examined by immunohistochemical analysis agreed to undergo DC vaccine therapy. The positive staining of WT1 in tumor cells was observed in 25.3% of patients, with only 8.5% of them showing moderate to strong expression; moreover, WT1 tended to localize in the nucleus and cytoplasm. A positive staining of tumor cells by an anti-MHC class l monoclonal antibody was observed in 98.6% and by an anti-MUC1 monoclonal antibody in 76.8% of the patients. In relation to the application of cancer-specific immunotherapy, these findings provide useful information for determining the efficacy of MUC1- and WT1-targeted therapy. PMID- 27354646 TI - Safety and Anti-tumor Effects of Docetaxel Plus Cisplatin in Intermediate- and High-risk Endometrial Cancer. AB - BACKGROUND: Endometrial cancer (EC) has a poor prognosis due to drug resistance. PATIENTS AND METHODS: We evaluated the safety and efficacy of adjuvant combination chemotherapy with docetaxel plus cisplatin ((DP) docetaxel, 70 mg/m(2); cisplatin, 60 mg/m(2); every 28 days) in EC patients at intermediate risk (IR) or high-risk (HR) for recurrence. RESULTS: Sixty-four patients diagnosed with EC were enrolled. Stage-I, -II, -III and -IV disease was noted in 23, 7, 28 and 6 patients, respectively. Histopathological analyses revealed that 56, 3, 1 and 4 patients had endometrioid, serous, clear-cell or "other" types of carcinoma. Grade-3/4 hematologic toxicities were found at 80% and 95% in patients in IR and HR groups, respectively. In IR and HR groups, mean progression-free (PFS) survival was 69.5 and 29.5, while overall survival (OS) was 59.6 and 47.5 months, respectively. CONCLUSION: DP may be clinically safe and useful treatment for EC. PMID- 27354647 TI - Retrospective Analysis of Growth Speed of 54 Lesions of Colitis-associated Colorectal Neoplasia. AB - AIM: This study used a multicenter questionnaire survey to evaluate the morphology and progression of the initial lesion in cases of colitis-associated colorectal neoplasia (CRN). PATIENTS AND METHODS: Endoscopic images of lesions that had been definitively diagnosed as CRN by pathological examination were retrospectively reviewed. RESULTS: This resulted in the identification of 54 initial lesions in 49 patients. The 54 initial lesions fell into the following categories: 22 endoscopically visible localized lesions consisting of 18 elevated lesions and 4 depressed lesions, as well as 32 lesions that were not endoscopically visible as localized and consisted of 20 active-phase mucosal lesions and 12 remission-phase mucosal lesions. Nineteen of the lesions eventually became advanced cancers, while 35 lesions eventually became early stage cancers. The final lesions were 40 elevated lesions, 5 flat or depressed lesions and 9 stenotic lesions. The form of growth of the advanced cancers was progressive stenosis or increased elevation. For approximately 69% of the early stage cancers, the growth form was increasing elevation or development of elevation. For 73.6% of the advanced cancers, the initial lesion underwent rapid growth and became advanced cancer within 3 years; they accounted for 25.9% of the total cancers. Approximately 40% of the initial lesions of CRN were endoscopically visible as localized lesions, while approximately 60% were judged to be inflammatory mucosal lesions. CONCLUSION: It will be necessary to proactively take biopsy inflammatory mucosal lesions in order to discover tumors early and periodic surveillance should be performed with the knowledge that tumors may grow very quickly. PMID- 27354648 TI - Adoptive Chemoimmunotherapy Using Activated alphabeta T Cells for Stage IV Colorectal Cancer. AB - BACKGROUND/AIM: Adoptive immunotherapy of cancer is evolving with the development of novel technologies that generate proliferation of large numbers of alphabeta and gammadelta T cells. We evaluated the safety and efficacy of the combination of adoptive immunotherapy using alphabeta T cells with chemotherapy for stage IV colorectal cancer (CRC). PATIENTS AND METHODS: Fifteen patients with advanced or recurrent CRC received XELOX + bevacizumab + ex vivo expanded alphabeta T lymphocytes as a first-line chemoimmunotherapy. RESULTS: Median age of the 15 patients (4 men, 11 women) was 65 years (range=49-80). Median progression-free survival was 21.3 months. Response rate was 80% (complete response (CR)=26.7%, partial response (PR)=53.3%, stable disease (SD)=20% and progressive disease (PD)=0%). Most adverse events were mild to moderate regarding their intensity and immunotherapy-associated toxicity was minimal. CONCLUSION: Combination of adoptive alphabeta T cell immunotherapy with chemotherapy for stage IV CRC is feasible and safe. PMID- 27354649 TI - Clinical Effects of Orally Administered Lipopolysaccharide Derived from Pantoea agglomerans on Malignant Tumors. AB - BACKGROUND/AIM: It has been reported that oral administration of lipopolysaccharide (LPS) recovers an individual's immune condition and induces the exclusion of foreign matter, inflammation and tissue repair. We orally administered LPS from the wheat symbiotic bacteria Pantoea agglomerans, which has been ingested and proven to be safe, to cancer patients. Our observation of clinical improvements resulting from this treatment are reported. PATIENTS AND METHODS: Sixteen cancer patients who exhibited declined small intestinal immune competence were treated between June and September, 2015. Diagnosis was based on our evaluation on small intestinal immune competence and macrophage activity. RESULTS: The state of malignant tumors at 3 months after starting this treatment was complete recovery for 3 cases, remission for 7 cases, maintenance for 4 cases, exacerbation for 1 case and death for 1 case (total response rate=62.5%). Small intestinal immune competence and macrophage activity recovered in all cases, suggesting that oral administration of LPS contributes to disease improvement. No clear side-effects that appeared to be related to LPS intake were noted. CONCLUSION: Intake of an appropriate level of Pantoea agglomerans LPS recovers small intestinal immune competence and macrophage activity, contributing to improvement of malignant tumors' therapy. PMID- 27354650 TI - Safety of Emulsifying Lipid Formulation Containing Omega-3 Polyunsaturated Fatty Acids for Patients with Crohn's Disease. AB - BACKGROUND/AIM: The efficacy of omega-3 supplementation by oral capsule for patients with Crohn's disease (CD) remains controversial. We investigated the safety and efficacy of an omega-3 emulsified formulation. PATIENTS AND METHODS: Six patients with CD in remission participated in this open-label clinical trial. Patients ingested one bottle (100 ml) of the test formulation (IMARK S(r)) daily for 28 days. After a 1-month washout period, patients ingested two bottles of the formulation daily for 28 days. Anthropometric and blood tests were performed before and after each intervention. RESULTS: The omega-3 emulsifying formulation was safe with minimal side-effects. Body weight and body-mass index were not altered; however, CD activity index scores tended to decrease after ingested one bottle of formulation. Blood tests revealed no severe adverse effects. CONCLUSION: Supplementation with an omega-3 emulsifying formulation can be safe and useful for maintaining remission in patients with CD and warrants further studies. PMID- 27354651 TI - Current State of and Problems Related to Cancer of the Intestinal Tract Associated with Crohn's Disease in Japan. AB - BACKGROUND/AIM: Cancer of the intestinal tract (small and large intestine) associated with Crohn's disease has a low incidence but can be fatal if it develops. Thus, the key question is how to deal with this type of cancer. The current study surveyed major medical facilities that treat inflammatory bowel disease (IBD) surgically in Japan in order to examine the clinical features of cancer of the intestinal tract associated with Crohn's disease and explore ways to deal with this cancer in the future. PATIENTS AND METHODS: Sixteen major medical facilities that treat IBD surgically were surveyed regarding cancer of the intestinal tract associated with Crohn's disease. The medical facilities had treated 3,454 patients with Crohn's disease, 122 of whom had developed intestinal cancer. The medical facilities were surveyed regarding those 122 patients. RESULTS: The incidence of intestinal cancer associated with Crohn's disease has increased yearly. Cancer most often developed in the left side of the colon and, particularly, in the rectum and anal canal. Seventy-six percent of cases were diagnosed preoperatively, 4% were diagnosed intraoperatively, while the remaining 20% were diagnosed pathologically after surgery. The most prevalent histological type of cancer was mucinous carcinoma (50%). Forty-two percent of cancers were differentiated, with 4% being poorly differentiated. The surgical procedure performed most often (67%) was abdominoperineal resection. The 5-year survival rate by stage was 88% for Stage I, 68% for Stage II, 71% for Stage IIIa, 25% for Stage IIIb and 0% for Stage IV. Overall, the 5-year survival rate was 52%. CONCLUSION: Gastrointestinal (GI) cancer associated with Crohn's disease had an incidence of 3.5%, but also involved a poor prognosis with a 5-year survival rate of 52%. Early detection through surveillance is crucial to improving the prognosis for patients. However, surveillance of the intestinal tract with endoscopy or contrast studies is technically and diagnostically hampered by Crohn's disease and intestinal strictures. A biopsy of the anal canal, a common site of cancer, can readily be performed and constitutes the first step in surveillance. PMID- 27354652 TI - Case Report: A Non-small Cell Lung Cancer Patient Treated with GcMAF, Sonodynamic Therapy and Tumor Treating Fields. AB - BACKGROUND/AIM: Macrophage activating factor (MAF)-based immunotherapy has a wide application for use in treating many diseases via macrophage activation. Sonodynamic therapy (SDT) using low-intensity ultrasound and tumor treating field (TTF) therapy are novel therapeutic modalities. SDT is usually combined with ozone therapy to improve local hypoxia within the tumor environment. CASE REPORT: We treated a 77-year-old male diagnosed with non-small cell lung cancer ((NSCLC) stage 3B) using second-generation serum GcMAF and oral colostrum MAF-based immunotherapy combined with SDT, TTF and ozone therapies. RESULTS: This case report demonstrates that GcMAF, oral colostrum MAF, SDT, TTF and ozone therapy can be used for NSCLC without adverse effects. CONCLUSION: This case report suggests a new concept of cancer treatment using local destruction of cancer tissue, in this case conducted with SDT and TTF therapy, to be used in combination with serum GcMAF and colostrum MAF immunotherapy as a systemic treatment. PMID- 27354653 TI - Case Report: GcMAF Treatment in a Patient with Multiple Sclerosis. AB - BACKGROUND/AIM: Gc protein-derived macrophage-activating factor (GcMAF) has various functions as an immune modulator, such as macrophage activation, anti angiogenic activity and anti-tumor activity. Clinical trials of second-generation GcMAF demonstrated remarkable clinical effects in several types of cancers. Thus, GcMAF-based immunotherapy has a wide application for use in the treatment of many diseases via macrophage activation that can be used as a supportive therapy. Multiple sclerosis (MS) is considered to be an autoimmune disorder that affects the myelinated axons in the central nervous system (CNS). This study was undertaken to examine the effects of second-generation GcMAF in a patient with MS. RESULTS: This case study demonstrated that treatments of GcMAF in a patient with MS have potent therapeutic actions with early beneficial responses, especially improvement of motor dysfunction. CONCLUSION: GcMAF shows therapeutic potency in the treatment of MS. PMID- 27354654 TI - Expression of HSP27 in Hepatocellular Carcinoma. AB - BACKGROUND/AIM: Heat-shock protein 27 (HSP27), a low molecular weight stress protein, is recognized as a molecular chaperone. The expression of HSP27 has been detected in some human tumors and while HSP27 is phosphorylated as a reresponse to stress, the function of phosphorylated HSP27 (p-HSP27) is not known. The aim of this study was to investigate what kind of effect expression of HSP27 and p HSP27 in HCC has on clinicopathological characteristics and prognosis. MATERIALS AND METHODS: An immunohistochemical study for HSP27 and p-HSP27 was performed on 194 resected HCC cases. We analyzed the correlation of HSP27 expression with various parameters statistically. RESULTS: There was no correlation between expression of HSP27 and the clinicopathological characteristics and prognosis from the analysis of 194 cases. From the analysis of the hepatitis C virus (HCV) positive group of 142 cases, those that were p-HSP27-positive had a larger tumor diameter and the portal vein invasion rate was high. CONCLUSION: The expression of total HSP27 may serve as a new, clinically useful marker of HCC. In addition, the present study suggests that the expression of phosphorylated HSP27 is useful in the screening and grading of HCC occurring in the setting of HCV. PMID- 27354655 TI - Nuclear Y-Box-binding Protein-1 Expression Predicts Poor Clinical Outcome in Stage III Colorectal Cancer. AB - BACKGROUND/AIM: Y-Box-binding protein-1 (YB-1), a DNA/RNA-binding protein, is an important oncogenic transcription and translation factor. We aimed to evaluate the relationships between nuclear YB-1 expression, epidermal growth factor receptor (EGFR) status, and poor clinical outcomes in patients with colorectal cancer (CRC). MATERIALS AND METHODS: Nuclear YB-1 expression was immunohistochemically analyzed in CRC tissues obtained from 124 patients who underwent curative resection between 2005 and 2008. Correlations between nuclear YB-1 expression, various clinicopathological characteristics, EGFR status, and prognostic factors were evaluated. RESULTS: High-grade nuclear YB-1 expression was detected in 62.9% of cases and was found to be an independent predictor of poorer overall survival (p<0.001) and relapse-free survival (p<0.001). A trend was also observed towards a positive correlation between nuclear YB-1 expression and EGFR status (p=0.051). CONCLUSION: Nuclear YB-1 expression is a useful prognostic biomarker that correlates with EGFR status in patients with CRC. PMID- 27354656 TI - Antihypertensive Medication Use in Older Patients Transitioning from Chronic Kidney Disease to End-Stage Renal Disease on Dialysis. AB - BACKGROUND AND OBJECTIVES: The transition from CKD to ESRD can be particularly unstable, with high rates of death and hospitalizations. Few studies have examined medication use during this critical period. We examined patterns of antihypertensive medication use from the four quarters before and eight quarters after incident ESRD treated with maintenance dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used the US Renal Data System to identify patients aged >=67 years initiating dialysis for ESRD between January 2008 and December 2010 with Medicare Part D and a low-income subsidy. We ascertained the incidence of AKI and hyperkalemia during each quarter on the basis of having at least 1 payment claim for the condition. We used Poisson regression with robust SEMs to formally test for changes in the trend and level of antihypertensive medication use in a series of intervention analyses. RESULTS: The number of antihypertensive drugs used increased as patients neared ESRD, peaking at an average of 3.4 in the quarter immediately preceding dialysis initiation, then declining to 2.2 medications by 2 years later. Angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use was stable at approximately 40%, even among patients with coronary disease and systolic heart failure, and did not correlate with AKI or hyperkalemia. Dialysis initiation was associated with a 40% (95% confidence interval, 38% to 43%) lower adjusted level of diuretic use, which continued to decline after ESRD. Three- and four-drug combinations that included a diuretic were most common before ESRD, whereas after ESRD, one- and two-drug beta-blocker or calcium-channel blocker-based combinations were most common. CONCLUSIONS: The use of antihypertensive medications, particularly angiotensin converting enzyme inhibitor/angiotensin II receptor blockers and diuretics, may be suboptimal during the transition from CKD to ESRD, especially in patients with coronary disease or systolic heart failure. Future studies are needed to identify strategies to increase the appropriate use of antihypertensive medications during this critical transition period. PMID- 27354658 TI - Correction. PMID- 27354657 TI - Antihypertensive Medication in Patients Pre- and Postdialysis: Still Hazy After All These Years. PMID- 27354660 TI - Reproductive traits affect the rescue of valuable and endangered multipurpose tropical trees. AB - Conservation strategies are urgently needed in Tropical areas for widely used tree species. Increasing numbers of species are threatened by overexploitation and their recovery might be poor due to low reproductive success and poor regeneration rates. One of the first steps in developing any conservation policy should be an assessment of the reproductive biology of species that are threatened by overexploitation. This work aimed to study the flowering biology, pollination and breeding system of V. doniana, a multipurpose threatened African tree, as one step in assessing the development of successful conservation strategies. To this end, we studied (1) traits directly involved in pollinator attraction like flowering phenology, flower numbers and morphology, and floral rewards; (2) abundance, diversity and efficiency of flower visitors; (3) breeding system, through controlled hand-pollination experiments involving exclusion of pollinators and pollen from different sources; and (4) optimal conditions for seed germination. The flowering phenology was asynchronous among inflorescences, trees and sites. The flowers produced a large quantity of pollen and nectar with high sugar content. Flowers attracted diverse and abundant visitors, counting both insects and birds, and efficient pollinators included several Hymenoptera species. We detected no spontaneous self-pollination, indicating a total dependence on pollen vectors. Vitex doniana is self-compatible and no inbreeding depression occurred in the first developmental stages. After extraction of the seed from the fruit, seed germination did not require any particular conditions or pre-treatments and the seeds showed high germination rates. These pollination and breeding characteristics as well as germination potential offer the required conditions to develop successful conservation strategies. Protection, cultivation and integration in agroforestry systems are required to improve the regeneration of the tree. PMID- 27354659 TI - Silent Cerebral Microbleeds and Longitudinal Risk of Renal and Cardiovascular Events in Patients with CKD. AB - BACKGROUND AND OBJECTIVES: In the general population, the presence of cerebral microbleeds on T2*-weighted magnetic resonance imaging has been reported to be a predictor of future stroke. Patients with CKD have a high prevalence of microbleeds and are at higher risk of ESRD as well as cardiovascular disease, including stroke. Because endothelial dysfunction is the common pathophysiology among microbleeds, CKD, and cardiovascular disease, we hypothesized that the presence of microbleeds would be an important predictor of composite outcome, including both cardiovascular disease and renal events, in those with CKD. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: This was a prospective cohort study of 404 patients with CKD who underwent T2*-weighted magnetic resonance imaging for this study between January of 2008 and January of 2011. The primary outcome was composite of cardiovascular and renal outcomes. Cardiovascular outcomes included cardiovascular death, the new onset of myocardial infarction, coronary revascularization, stroke, and amputation/revascularization because of peripheral artery disease. Renal outcomes included doubling of the serum creatinine level and development of ESRD requiring dialysis or transplantation. RESULTS: At baseline, microbleeds were present in 83 (20.5%) patients. During the follow-up median period of 2.3 years, 124 of the 404 patients experienced the composite outcome. The presence of microbleeds was associated with higher risk for the composite outcome in an unadjusted Cox model, and it remained significant after adjustment for age, sex, diabetes, and systolic BP (hazard ratio [HR], 2.58; 95% confidence interval [95% CI], 1.68 to 3.46 for composite outcome; hazard ratio, 2.41; 95% CI, 1.55 to 3.77 for renal outcome; hazard ratio, 3.46; 95% CI, 1.62 to 7.43 for cardiovascular disease outcome). CONCLUSIONS: In patients with CKD, the presence of microbleeds is a novel and independent predictor of both renal and cardiovascular disease end points. PMID- 27354661 TI - The chemical identity of intervessel pit membranes in Acer challenges hydrogel control of xylem hydraulic conductivity. AB - Ion-mediated enhancement of the hydraulic conductivity of xylem tissue (i.e. the ionic effect) has been reported for various angiosperm species. One explanation of the ionic effect is that it is caused by the swelling and shrinking of intervessel pit membranes due to the presence of pectins and/or other cell-wall matrix polymers such as heteroxylans or arabinogalactan-proteins (AGPs) that may contain acidic sugars. Here, we examined the ionic effect for six Acer species and their pit membrane chemistry using immunocytochemistry, including antibodies against glycoproteins. Moreover, anatomical features related to the bordered pit morphology and vessel dimensions were investigated using light and electron microscopy. The ionic effect varied from 18 % (+/- 9) to 32 % (+/- 13). Epitopes of homogalacturonan (LM18) and xylan (LM11) were not detected in intervessel pit membranes. Negative results were also obtained for glycoproteins (extensin: LM1, JIM20; AGP glycan: LM2), although AGP (JIM13)-related epitopes were detected in parenchyma cells. The mean vessel length was significantly correlated with the magnitude of the ionic effect, unlike other pit or vessel-related characteristics. Our results suggest that intervessel pit membranes of Acer are unlikely to contain pectic or other acidic polysaccharides. Therefore, alternative explanations should be tested to clarify the ionic effect. PMID- 27354663 TI - Correction. PMID- 27354664 TI - Correction. PMID- 27354665 TI - Correction. PMID- 27354666 TI - Correction. PMID- 27354667 TI - Correction. PMID- 27354670 TI - A woman with a red eye from a carotid-cavernous sinus fistula. PMID- 27354668 TI - The Future of Immunotherapy in the Treatment of Small Cell Lung Cancer. AB - : Small cell lung cancer (SCLC), which accounts for 10%-15% of lung cancer cases, is an aggressive disease characterized by rapid growth and early widespread metastasis. Although up to 80% of patients respond to first-line chemotherapy, most eventually relapse, and there are no approved agents beyond the second line. Despite the high incidence of mutations in SCLC, to date no targeted therapy has shown a benefit for this patient population, and systemic treatment has not changed significantly during the past 3 decades. Given that extensive-stage SCLC has a 5-year survival rate of only 1%-2%, novel therapies are desperately needed. Recent evidence shows that the immune system is capable of generating antitumor responses against various tumors, including lung cancer, suggesting that immunotherapy may be a viable therapeutic approach to the treatment of patients with SCLC. Of the immunotherapies being investigated for patients with SCLC, antibodies that target the programmed cell death protein-1 (nivolumab and pembrolizumab) and cytotoxic T-lymphocyte antigen-4 (ipilimumab) immune checkpoint pathways are perhaps the most promising. Because these immune checkpoint pathways, which under normal circumstances function to protect healthy tissues from damage during inflammatory responses and maintain self-tolerance, can help tumor cells evade elimination by the immune system, they represent potential therapeutic targets. This review discusses the rationale for immunotherapy and the early clinical results of immunotherapeutic agents being investigated in SCLC. IMPLICATIONS FOR PRACTICE: Small cell lung cancer (SCLC) is an aggressive lung cancer subtype. Despite sensitivity to first-line chemotherapy, SCLC has high recurrence rates, and responses to second-line treatments are poor. Recent evidence shows that the immune system is capable of generating responses against various tumors, including lung cancer, suggesting that immunotherapy may be a viable approach for patients with SCLC. Of several immunotherapies being investigated, antibodies that target the programmed cell death protein-1 (nivolumab and pembrolizumab) and cytotoxic T-lymphocyte antigen 4 (ipilimumab) immune checkpoint pathways are among the most promising for patients with SCLC and are the focus of this review. PMID- 27354671 TI - Doctors left to define foreseeable death in new law. PMID- 27354669 TI - Integration of Stereotactic Body Radiation Therapy With Tyrosine Kinase Inhibitors in Stage IV Oncogene-Driven Lung Cancer. AB - : Genotype-based selection of patients for targeted therapies has had a substantial impact on the treatment of non-small cell lung cancers (NSCLCs). Tyrosine kinase inhibitors (TKIs) directed at cancers driven by oncogenes, such as epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements, often achieve dramatic responses and result in prolonged survival compared with chemotherapy. However, TKI resistance invariably develops. Disease progression can be limited to only one or a few sites and might not be symptomatic, raising the important question of whether this type of oligoprogression warrants a change in systemic therapy or consideration of local treatment. Recent clinical observations suggest a growing role for stereotactic body radiation therapy (SBRT) in the treatment of oligoprogressive and perhaps even oligopersistent disease (primary and/or metastases) in oncogene-driven NSCLC. SBRT might allow patients to continue with existing TKI treatments longer and delay the need to switch to other systemic options. We review the current data with regard to the use of SBRT for metastatic NSCLC and particularly oncogene-driven disease. Although there is great promise in the marriage of targeted therapies with SBRT, prospective data are urgently needed. In the meantime, such strategies are being used in carefully selected patients, with risk-adapted SBRT dose-fractionation regimens used to optimize the therapeutic index. IMPLICATIONS FOR PRACTICE: Stereotactic body radiation therapy (SBRT) or SBRT-like treatments are increasingly being used for oligoprogression in patients with oncogene-driven non-small cell lung cancer. This approach allows patients to extend the duration of tyrosine kinase inhibitor therapy and has the potential to prolong survival times. Careful patient selection and risk-adapted radiation dosing is of critical importance to minimize toxicity and preserve patient quality of life. PMID- 27354672 TI - Thoracic outlet syndrome. PMID- 27354673 TI - Cochrane continues to seek stable funding. PMID- 27354674 TI - Acting to the very limits of what you can do. PMID- 27354675 TI - College complaints to CMPA increase. PMID- 27354676 TI - Improving patient-centred care for rheumatoid arthritis. PMID- 27354677 TI - Common state mechanisms regulating tribal tobacco taxation and sales, the USA, 2015. AB - BACKGROUND: Native American tribes, as sovereign nations, are exempt from state tobacco excise taxation, and self-govern on-reservation activity in the USA. Under Federal law, state excise taxes are owed by non-members purchasing tobacco on tribal land, but states are limited in how they enforce or collect these taxes. This study highlights the various policy approaches that states have taken to regulate tobacco sales on tribal lands given jurisdictional challenges. METHODS: State laws (statutes, regulations and case law), Attorney General opinions, and revenue notices and rulings effective as of 1 January 2015 for all 50 states and the District of Columbia were compiled using Boolean searches in Lexis-Nexis and Westlaw. Laws were limited to those addressing taxation compacts or tobacco sales involving tribal entities. Master Settlement Agreement laws and non-codified tribal codes/compacts were excluded. RESULTS: Twenty of the 34 states with tribal lands address tribal tobacco sales. Fourteen states address intergovernmental compacts: 11 are tobacco specific, and suggest or require specific provisions. Fifteen states address tribal tax stamps: 2 explicitly prohibit stamping tribally sold products, 9 stamp all products, and 4 stamp some. Prepayment of excise tax is required in 12 states: 6 on all products, 4 on products in excess of quota, and 2 on products sold by non-tribal retailers. 6 states use quotas to limit tax-free tobacco available to tribes. CONCLUSIONS: Many states with a tribal presence have no formal strategies for non-members purchasing tobacco on tribal lands. Formalising policies and harmonising tax rates may assist states in collecting tax revenue from non-tribal consumers. PMID- 27354678 TI - Analysis of British American Tobacco's questionable use of privilege and protected document claims at the Guildford Depository. AB - BACKGROUND: Tobacco companies have a documented history of attempting to hide information from public scrutiny, including inappropriate privilege claims. The 1998 Minnesota Consent Judgement created two depositories to provide public access to discovered documents. Users raised concerns about the access conditions and ongoing integrity of the Guildford Depository collection operated until 2015 by British American Tobacco (BAT). METHODS: A metadata search of the Legacy Tobacco Documents Library identified inconsistent privilege claims, and duplicates of documents withheld by BAT from public visitors. A review of the validity of claims, for documents obtained through these searches, was conducted against recognised legal definitions of privilege. FINDINGS: BAT has asserted inappropriate privilege claims over 49% of the documents reviewed (n=63). The quantity of such claims and consistency of the stated rationale for the privilege claims suggest a concerted effort rather than human error. CONCLUSIONS: There was insufficient attention given to the operation of the Guildford Depository by the original plaintiffs, including to the subsequent use of privilege claims. Appropriate access to these documents, commensurate with the terms of legal settlements creating the collection, was critical given their public interest value for enhancing understanding of industry strategies and activities, informing of policy interventions, and for holding the industry to account. Future legal settlements should prevent defendants from subsequently withholding disclosed documents, aside from those legitimately privileged, from public view. Control of publicly disclosed documents should not be placed back into the hands of defendant tobacco companies. Plaintiffs also need to invest adequate resources into policing claims of legal privilege. PMID- 27354679 TI - Integrating the impact of cigarette and waterpipe tobacco use among adolescents in the Eastern Mediterranean Region: a cross-sectional, population-level model of toxicant exposure. AB - BACKGROUND: Waterpipe smoking is more prevalent than cigarette smoking among adolescents in the Eastern Mediterranean Region (EMR); however, simple prevalence masks complex waterpipe smoking patterns and makes uncertain its contribution to risk of tobacco-related harm. This study aimed to integrate the impact of cigarette and waterpipe tobacco use on toxicant exposure among EMR adolescents. METHODS: A cross-sectional model made equivalent individual-level toxicant exposure data for cigarettes and waterpipes, and aggregated it to 23 countries in the EMR using the Global Youth Tobacco Survey. The waterpipe model adjusted for estimated frequency of use, session duration and sharing behaviours. The final model included 60 306 12-17-year olds, and modelled as outcomes nicotine, carbon monoxide (CO) and 14 carcinogens. Sensitivity analyses substantially reduced session duration and proportion of solo use. RESULTS: Our model suggests waterpipe use may contribute a median of 36.4% (IQR 26.7-46.8%, n=16) of the total toxicant exposure from tobacco, and may reach up to 73.5% and 71.9% of total CO and benzene exposure, respectively. Sensitivity analyses reduced all values by 4.3-21.0%, but even the most conservative scenarios suggested over 50% of benzene and CO exposure was from waterpipe use. Between 69.2% and 73.5% of total toxicant exposure derived from dual cigarette and waterpipe users, who smoked cigarettes and waterpipe more frequently and intensely than single users. CONCLUSIONS: More research is warranted to refine our model's parameters. Tobacco control researchers should consider a move towards a single unit of measure for cigarette and waterpipe tobacco exposure in order to better inform health policy. PMID- 27354681 TI - Daytime Mouthpiece for Continuous Noninvasive Ventilation in Individuals With Amyotrophic Lateral Sclerosis. AB - BACKGROUND: Noninvasive ventilation (NIV) is commonly used to provide ventilatory support for individuals with amyotrophic lateral sclerosis (ALS). Once 24-h ventilation is required, the decision between invasive tracheostomy ventilation and palliation is often faced. This study describes the use and outcomes of daytime mouthpiece ventilation added to nighttime mask ventilation for continuous NIV in subjects with ALS as an effective alternative. METHODS: This was a retrospective study of 39 subjects with ALS using daytime mouthpiece ventilation over a 17-y period. RESULTS: Thirty-one subjects were successful with mouthpiece ventilation, 2 were excluded, 2 stopped because of lack of motivation, and 4 with bulbar subscores of the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (b-ALSFRS-R) between 0 and 3 physically failed to use it consistently. No subject in the successful group had a b-ALSFRS-R score of <6. Thirty of the successful subjects were able to generate a maximum insufflation capacity - vital capacity difference with lung volume recruitment. The median (range) survival to tracheostomy or death from initiation of nocturnal NIV and mouthpiece ventilation were 648 (176-2,188) and 286 (41-1,769) d, respectively. Peak cough flow with lung-volume recruitment >180 L/min at initiation of mouthpiece ventilation was associated with a longer survival (637 +/- 468 vs 240 +/- 158 d (P = .01). CONCLUSIONS: Mouthpiece ventilation provides effective ventilation and prolonged survival for individuals with ALS requiring full-time ventilatory support and maintaining adequate bulbar function. PMID- 27354682 TI - Resveratrol lowers synovial hyperplasia, inflammatory markers and oxidative damage in an acute antigen-induced arthritis model. AB - OBJECTIVE: The present study aimed to determine the protective effects of dietary supplementation with resveratrol (RSV) in an acute antigen-induced arthritis (AIA) model. METHODS: Rats were randomly divided into three groups: control, AIA and RSV-treated AIA group. RSV (12.5 mg/kg/day) was given orally for 8 weeks before induction of AIA and until the end of the experiment (48 h after intra articular injection). The control and AIA animals were administered 100 MUl of water. Results were evaluated by macroscopic observation, histopathology and immunohistochemistry for anti-PCNA, macrophages (CD68), T lymphocytes (CD3), monocyte chemoattractant protein-1 and 8-oxo-7,8-dihydro-2'-deoxyguanine (a marker of DNA damage). Cytokine-induced neutrophil chemoattractant-1 in serum and peroxidase activity in synovial tissue were measured using commercial kits. RESULTS: At the end of the study, RSV significantly reduced knee swelling. Likewise, the histological score of synovial tissue also reduced significantly. The arthritis-protective effects were associated with a significant decrease in PCNA, CD68, CD3 and monocyte chemoattractant protein-1 staining, as well as a reduction in serum concentrations of cytokine-induced neutrophil chemoattractant 1. RSV treatment also decreased the level of the marker of DNA damage, 8-oxo-7,8 dihydro-2'-deoxyguanine. Accordingly, peroxidase activity in the synovial tissue was up-regulated. CONCLUSION: Dietary supplementation with RSV lowers the main pathological hallmarks of RA disease in an acute model of AIA. RSV may represent a promising strategy in controlling the severity of RA. PMID- 27354683 TI - Interferon alpha kinoid induces neutralizing anti-interferon alpha antibodies that decrease the expression of interferon-induced and B cell activation associated transcripts: analysis of extended follow-up data from the interferon alpha kinoid phase I/II study. AB - OBJECTIVE: IFN alpha Kinoid (IFN-K) is a therapeutic vaccine composed of IFNalpha2b coupled to a carrier protein. In a phase I/II placebo-controlled trial, we observed that IFN-K significantly decreases the IFN gene signature in whole blood RNA samples from SLE patients. Here, we analysed extended follow-up data from IFN-K-treated patients, in order to evaluate persistence of neutralizing anti-IFNalpha Abs antibodies (Abs), and gene expression profiling. METHODS: Serum and whole blood RNA samples were obtained in IFN-K-treated patients included in the follow-up study, in order to determine binding and neutralizing anti-IFNalpha Ab titres, and perform high-throughput transcriptomic studies. RESULTS: Neutralization studies of 13 IFNalpha subtypes demonstrated the polyclonal nature of the Ab response induced by IFN-K. Follow-up analyses in six patients confirmed a significant correlation between neutralizing anti-IFNalpha Ab titres and decrease in IFN scores compared to baseline. These analyses also revealed an inhibitory effect of IFNalpha blockade on the expression of B cell associated transcripts. CONCLUSIONS: IFN-K induces a polyclonal anti-IFNalpha response that decreases IFN- and B cell-associated transcripts. TRIAL REGISTRATION: ClinicalTrials.gov, clinicaltrials.gov, NCT01058343. PMID- 27354684 TI - The effectiveness of a real life dose reduction strategy for tumour necrosis factor inhibitors in ankylosing spondylitis and psoriatic arthritis. AB - OBJECTIVE: To determine feasibility of TNF inhibitor (TNFi) dose reduction for severe AS and PsA patients. METHODS: A retrospective study in a real-world setting. Criteria for dose reduction of TNFi included BASDAI < 4 for ?6 months in AS; or DAS28-ESR ? 3.2 for ?6 months in PsA. TNFi dose was reduced by one-third. Patients who flared (BASDAI > 4 in AS or DAS28-ESR > 3.2 in PsA) were re escalated to standard treatment dose. RESULTS: Twenty-six per cent (33/125) of AS and 18% (15/83) of PsA patients fulfilled criteria and underwent TNFi dose reduction. Fifty-eight per cent (19/33) of AS and 60% (9/15) of PsA patients maintained TNFi dose reduction for mean (s.d) of 1.0 (0.8) years. Reinstating standard dose of TNFi recaptured low disease activity in all patients who failed dose reduction within 24 weeks, with no statistically significant difference in mean BASDAI compared with those maintaining TNFi dose reduction in AS at 24 weeks [mean (s.d) BASDAI 2.4 (1.1) vs 1.9 (1.5), respectively (P = 0.229)]; however in PsA, those who failed dose reduction had higher disease activity compared with patients maintained on TNFi dose reduction at 24 weeks [mean (s.d) DAS28-ESR 2.7 (0.6) vs 1.3 (0.5), respectively (P ? 0.001)]. In PsA, a lower DAS28-ESR prior to dose reduction of TNFi was associated with more successful dose reduction. CONCLUSIONS: In a real-world setting, 60% of individuals with severe AS and PsA who achieve low disease activity can successfully reduce the dose of TNFi therapy by a third for a mean of 1 year. PMID- 27354685 TI - Estrogen-induced expression of tumor necrosis factor-like weak inducer of apoptosis through ERalpha accelerates the progression of lupus nephritis. AB - OBJECTIVES: Oestrogens have been shown to play key roles in the pathogenesis of SLE. The aim of this study was to investigate the roles and mechanisms of 17beta estradiol (E2) in TNF-like weak inducer of apoptosis (TWEAK) expression in LN. METHODS: Peripheral blood mononuclear cells (PBMCs) obtained from LN patients were used for in vitro experiments, while female MRL/lpr and MRL/MpJ mice were used for in vivo studies. E2, ICI 182 780 [estrogen receptor (ER)-selective antagonist], methyl-piperidino-pyrazole (MPP, ERalpha-selective modulator), lentivirus (LV)-TWEAK-short hairpin RNA (shRNA) and LV-control-shRNA treatments were used in this study. RESULTS: TWEAK mRNA expression in PBMCs was significantly increased following E2 treatment and downregulated after incubation with ICI 182 780 or MPP. Compared with sham-operated MRL/lpr mice, ovariectomized mice, treated with dimethyl sulphoxide vehicle alone, showed lower expression levels of renal TWEAK mRNA and protein. The expression of both mRNA and protein in ovariectomized mice was upregulated after E2 treatment and downregulated after ICI 182 780 or MPP co-treatment. Severe renal damage was observed in E2-treated ovariectomized mice, as were higher serum levels of IL-6, compared with dimethyl sulphoxide vehicle-treated ovariectomized mice. Co-treatment with LV-TWEAK-shRNA reversed these changes, and LV-control-shRNA treatment had no effect on them. CONCLUSION: Our results demonstrated that E2 plays an important role in the upregulation of TWEAK expression in LN, most likely through an ERalpha-dependent pathway, causing kidney damage. This provides a novel insight into the mechanisms of the E2-TWEAK signalling pathway in LN. PMID- 27354686 TI - Nonadherence to disease modifying antirheumatic drugs in the first year after diagnosis: comparing three adherence measures in early arthritis patients. AB - OBJECTIVES: The aim of this study was to compare three measurement methods for non-adherence to DMARDs in early arthritis patients: the Compliance Questionnaire Rheumatology (CQR), the intracellular uptake of MTX in the form of MTX polyglutamates (MTX-PGs) and electronic measurement with Medication Event Monitoring Systems (MEMS). METHODS: DMARD naive early arthritis patients were included in an ongoing cohort study. MEMS were used to measure adherence continuously, while every 3 months MTX-PGs were collected together with the CQR. The associations between the measures were estimated with Spearman rank correlations. Sensitivity and specificity of the CQR against a MEMS cut-off was compared at 3, 6, 9 and 12 months. The same applied to MTX-PGs against a MEMS cut off and MTX-PGs against a CQR cut-off. For the association between MEMS, the CQR and MTX-PGs, a multilevel linear regression model was performed with age, gender, weeks of treatment and MTX dosage as covariates. RESULTS: We included 206 patients. Non-adherence measured with MEMS varied over time and between DMARDs. The CQR score was not associated with MEMS non-adherence at 3, 9 and 12 months. At 9 months, MTX-PGs was associated with MEMS non-adherence, as well as with the CQR. All correlations were below 0.30. CONCLUSION: Associations between the three measures are weak. Explanations are individual differences in the uptake of MTX, and little variance in adherence between patients. Moreover, the measurement domains differ: perceptions (CQR), behaviour (MEMS) and pharmacokinetics (MTX). PMID- 27354687 TI - Neutrophil extracellular traps as a potential source of autoantigen in cocaine associated autoimmunity. AB - Objective: Exposure to illicit cocaine and its frequent adulterant, levamisole, is associated with ANCAs targeting neutrophil elastase (NE), neutropenia and vasculitic/thrombotic skin purpura. The mechanisms of cocaine/levamisole associated autoimmunity (CLAA) are unknown. The aim of this study was to assess the ability of cocaine and levamisole to induce the release of neutrophil extracellular traps (NETs), a potential source of autoantigen and tissue injury. Methods: We performed quantitative and qualitative assessment of NET formation in neutrophils from healthy donors exposed to either drug in vitro . In addition, IgG from sera of individuals with CLAA (CLAA-IgG) was assessed for its ability to enhance formation of, and to bind to, drug-induced NETs. Results: Both cocaine and levamisole could induce formation of NETs enriched in NE and, potentially, inflammatory mitochondrial DNA. Both drugs could also augment simultaneous release of B cell-activating factor belonging to the TNF family (BAFF). CLAA-IgG, but not IgG from healthy individuals, could potentiate drug-induced NETosis. Furthermore, CLAA-IgG, but not ANCA + control IgG, bound to drug-induced NETs in a pattern consistent with NE targeting. Conclusion: Both cocaine and levamisole may contribute to the development of ANCAs by inducing release of potentially inflammatory NETs in association with NE autoantigen and BAFF. Enhancement of drug-induced NET release by CLAA-IgG provides a potential mechanism linking vasculitis/pupuric skin disease to acute drug exposure in patients with CLAA. Further study of this under-recognized form of autoimmunity will be likely to provide mechanistic insight into ANCA-associated vasculitis and other diseases associated with NETosis. PMID- 27354689 TI - Cost-effectiveness of biologic compared with conventional synthetic disease modifying anti-rheumatic drugs in patients with rheumatoid arthritis: a Register study. AB - OBJECTIVE: The aim of this study was to explore the cost-effectiveness of biological DMARDs (bDMARDs) compared with conventional synthetic DMARDs (csDMARDs) for RA using real-world data from Finnish registers. METHODS: RA patients starting their first bDMARD and comparator patients using csDMARDs during 2007-11 were obtained from the National register of biologic treatments in Finland and the Jyvaskyla Central Hospital patient records. Propensity score matching was applied to adjust for differences between bDMARD and csDMARD users. Effectiveness was measured in quality-adjusted life years (QALY) and based on the register of biologic treatments in Finland and Jyvaskyla Central Hospital patient records, whereas the direct costs were obtained from relevant Finnish national registers. Patients were followed up for 2 years, and both costs and effectiveness for the second year were discounted at 3%. The incremental cost effectiveness ratio (ICER) with 95% CI was calculated based on bootstrapped mean costs and effectiveness. RESULTS: Of 1581 RA patients meeting study inclusion criteria, 552 bDMARD and 220 csDMARD users were included in analyses after matching. Mean costs for bDMARDs and csDMARDs were ?55 371 and ?24 879, while mean effectiveness was 1.23 and 1.20 QALYs, respectively. Consequent ICER was ?902 210/QALY. Results were confirmed in sensitivity analyses. CONCLUSION: The high incremental cost and the small, non-significant difference in effectiveness resulted in high ICER, suggesting that bDMARDs are not cost-effective. Regardless of matching, latent confounders may introduce bias to the results. PMID- 27354690 TI - Differences in the prevalence of ankylosing spondylitis in primary and secondary care: only one-third of patients are managed in rheumatology. AB - OBJECTIVE: Knowing not only the prevalence of SpA, but also the proportion managed in rheumatology, has implications for health care planning. The aims of this study were to determine the prevalence of SpA and the proportion managed in rheumatology and to examine differences in group characteristics. METHODS: For the primary care population, we used the Primary Care Clinical Informatics Unit Research (PCCIUR) electronic primary care database, covering one-third of the Scottish population. Patients with AS, and various extraspinal manifestations were identified using Read Codes. For secondary care, we used the Scotland Registry for Ankylosing Spondylitis, which collected data on clinically diagnosed AS patients >15 years of age seen in rheumatology clinics between 2010 and 2013. Prevalence estimate denominators were computed using the adult PCCIUR and Scottish 2011 mid-year population estimates, respectively. Differences in the characteristics of both patient groups were examined using simple descriptive statistics. RESULTS: The prevalence of AS in primary care was 13.4/10 000 (95% CI 12.8, 14.0) and 4.7/10 000 in rheumatology (95% CI 4.5, 4.9). Rheumatology patients were younger overall and at diagnosis (mean age 51 vs 62 years and 35 vs 38, respectively; both P < 0.001) and more likely to have a history of uveitis (34 vs 22%), IBD (12 vs 6%) and psoriasis (14 vs 6%) (all P < 0.001). CONCLUSIONS: This is the first study to estimate the prevalence of clinically diagnosed AS in primary and secondary care simultaneously, indicating that only one-third of patients are managed in rheumatology. This has important ramifications for health care planning and indicates a large 'silent' proportion of patients who may have serious pathology and would benefit from additional assessment in a specialist clinic. PMID- 27354688 TI - Ultrasound-detected tenosynovitis independently associates with patient-reported flare in patients with rheumatoid arthritis in clinical remission: results from the observational study STARTER of the Italian Society for Rheumatology. AB - OBJECTIVES: This study aimed to estimate the prevalence of US-detected tenosynovitis in RA patients in clinical remission and to explore its clinical correlates. METHODS: A total of 427 RA patients in clinical remission were consecutively enrolled from 25 Italian rheumatology centres. Tenosynovitis and synovitis were scored by US grey scale (GS) and power Doppler (PD) semi quantitative scoring systems at wrist and hand joints. Complete clinical assessment was performed by rheumatologists blinded to the US results. A flare questionnaire was used to assess unstable remission (primary outcome), HAQ for functional disability and radiographic erosions for damage (secondary outcomes). Cross-sectional relationships between the presence of each US finding and outcome variables are presented as odds ratios (ORs) and 95% CIs, both crude and adjusted for pre-specified confounders. RESULTS: The prevalence of tenosynovitis in clinical remission was 52.5% (95% CI 0.48, 0.57) for GS and 22.7% (95% CI 0.19, 0.27) for PD, while the prevalence of synovitis was 71.6% (95% CI 0.67, 0.76) for GS and 42% (95% CI 0.37, 0.47) for PD. Among clinical correlates, PD tenosynovitis associated with lower remission duration and morning stiffness while PD synovitis did not. Only PD tenosynovitis showed a significant association with the flare questionnaire [OR 1.95 (95% CI 1.17, 3.26)]. No cross sectional associations were found with the HAQ. The presence of radiographic erosions associated with GS and PD synovitis but not with tenosynovitis. CONCLUSIONS: US-detected tenosynovitis is a frequent finding in RA patients in clinical remission and associates with unstable remission. PMID- 27354691 TI - Inheritance-mode specific pathogenicity prioritization (ISPP) for human protein coding genes. AB - MOTIVATION: Exome sequencing studies have facilitated the detection of causal genetic variants in yet-unsolved Mendelian diseases. However, the identification of disease causal genes among a list of candidates in an exome sequencing study is still not fully settled, and it is often difficult to prioritize candidate genes for follow-up studies. The inheritance mode provides crucial information for understanding Mendelian diseases, but none of the existing gene prioritization tools fully utilize this information. RESULTS: We examined the characteristics of Mendelian disease genes under different inheritance modes. The results suggest that Mendelian disease genes with autosomal dominant (AD) inheritance mode are more haploinsufficiency and de novo mutation sensitive, whereas those autosomal recessive (AR) genes have significantly more non synonymous variants and regulatory transcript isoforms. In addition, the X-linked (XL) Mendelian disease genes have fewer non-synonymous and synonymous variants. As a result, we derived a new scoring system for prioritizing candidate genes for Mendelian diseases according to the inheritance mode. Our scoring system assigned to each annotated protein-coding gene (N = 18 859) three pathogenic scores according to the inheritance mode (AD, AR and XL). This inheritance mode-specific framework achieved higher accuracy (area under curve = 0.84) in XL mode. CONCLUSION: The inheritance-mode specific pathogenicity prioritization (ISPP) outperformed other well-known methods including Haploinsufficiency, Recessive, Network centrality, Genic Intolerance, Gene Damage Index and Gene Constraint scores. This systematic study suggests that genes manifesting disease inheritance modes tend to have unique characteristics. AVAILABILITY AND IMPLEMENTATION: ISPP is included in KGGSeq v1.0 (http://grass.cgs.hku.hk/limx/kggseq/), and source code is available from (https://github.com/jacobhsu35/ISPP.git). CONTACT: mxli@hku.hkSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27354692 TI - Accurate in silico prediction of species-specific methylation sites based on information gain feature optimization. AB - : As one of the most important reversible types of post-translational modification, protein methylation catalyzed by methyltransferases carries many pivotal biological functions as well as many essential biological processes. Identification of methylation sites is prerequisite for decoding methylation regulatory networks in living cells and understanding their physiological roles. Experimental methods are limitations of labor-intensive and time-consuming. While in silicon approaches are cost-effective and high-throughput manner to predict potential methylation sites, but those previous predictors only have a mixed model and their prediction performances are not fully satisfactory now. Recently, with increasing availability of quantitative methylation datasets in diverse species (especially in eukaryotes), there is a growing need to develop a species specific predictor. Here, we designed a tool named PSSMe based on information gain (IG) feature optimization method for species-specific methylation site prediction. The IG method was adopted to analyze the importance and contribution of each feature, then select the valuable dimension feature vectors to reconstitute a new orderly feature, which was applied to build the finally prediction model. Finally, our method improves prediction performance of accuracy about 15% comparing with single features. Furthermore, our species-specific model significantly improves the predictive performance compare with other general methylation prediction tools. Hence, our prediction results serve as useful resources to elucidate the mechanism of arginine or lysine methylation and facilitate hypothesis-driven experimental design and validation. AVAILABILITY AND IMPLEMENTATION: The tool online service is implemented by C# language and freely available at http://bioinfo.ncu.edu.cn/PSSMe.aspx CONTACT: jdqiu@ncu.edu.cnSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27354693 TI - A probabilistic approach for collective similarity-based drug-drug interaction prediction. AB - MOTIVATION: As concurrent use of multiple medications becomes ubiquitous among patients, it is crucial to characterize both adverse and synergistic interactions between drugs. Statistical methods for prediction of putative drug-drug interactions (DDIs) can guide in vitro testing and cut down significant cost and effort. With the abundance of experimental data characterizing drugs and their associated targets, such methods must effectively fuse multiple sources of information and perform inference over the network of drugs. RESULTS: We propose a probabilistic approach for jointly inferring unknown DDIs from a network of multiple drug-based similarities and known interactions. We use the highly scalable and easily extensible probabilistic programming framework Probabilistic Soft Logic We compare against two methods including a state-of-the-art DDI prediction system across three experiments and show best performing improvements of more than 50% in AUPR over both baselines. We find five novel interactions validated by external sources among the top-ranked predictions of our model. AVAILABILITY AND IMPLEMENTATION: Final versions of all datasets and implementations will be made publicly available. CONTACT: dsridhar@ucsc.edu. PMID- 27354694 TI - Evaluating the molecule-based prediction of clinical drug responses in cancer. AB - MOTIVATION: Molecule-based prediction of drug response is one major task of precision oncology. Recently, large-scale cancer genomic studies, such as The Cancer Genome Atlas (TCGA), provide the opportunity to evaluate the predictive utility of molecular data for clinical drug responses in multiple cancer types. RESULTS: Here, we first curated the drug treatment information from TCGA. Four chemotherapeutic drugs had more than 180 clinical response records. Then, we developed a computational framework to evaluate the molecule based predictions of clinical responses of the four drugs and to identify the corresponding molecular signatures. Results show that mRNA or miRNA expressions can predict drug responses significantly better than random classifiers in specific cancer types. A few signature genes are involved in drug response related pathways, such as DDB1 in DNA repair pathway and DLL4 in Notch signaling pathway. Finally, we applied the framework to predict responses across multiple cancer types and found that the prediction performances get improved for cisplatin based on miRNA expressions. Integrative analysis of clinical drug response data and molecular data offers opportunities for discovering predictive markers in cancer. This study provides a starting point to objectively evaluate the molecule-based predictions of clinical drug responses. CONTACT: jgu@tsinghua.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27354695 TI - ABAEnrichment: an R package to test for gene set expression enrichment in the adult and developing human brain. AB - : We present ABAEnrichment, an R package that tests for expression enrichment in specific brain regions at different developmental stages using expression information gathered from multiple regions of the adult and developing human brain, together with ontologically organized structural information about the brain, both provided by the Allen Brain Atlas. We validate ABAEnrichment by successfully recovering the origin of gene sets identified in specific brain cell types and developmental stages. AVAILABILITY AND IMPLEMENTATION: ABAEnrichment was implemented as an R package and is available under GPL (>= 2) from the Bioconductor website (http://bioconductor.org/packages/3.3/bioc/html/ABAEnrichment.html). CONTACTS: steffi_grote@eva.mpg.de, kelso@eva.mpg.de or michael_dannemann@eva.mpg.deSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27354696 TI - pSumo-CD: predicting sumoylation sites in proteins with covariance discriminant algorithm by incorporating sequence-coupled effects into general PseAAC. AB - MOTIVATION: Sumoylation is a post-translational modification (PTM) process, in which small ubiquitin-related modifier (SUMO) is attaching by covalent bonds to substrate protein. It is critical to many different biological processes such as replicating genome, expressing gene, localizing and stabilizing proteins; unfortunately, it is also involved with many major disorders including Alzheimer's and Parkinson's diseases. Therefore, for both basic research and drug development, it is important to identify the sumoylation sites in proteins. RESULTS: To address such a problem, we developed a predictor called pSumo-CD by incorporating the sequence-coupled information into the general pseudo-amino acid composition (PseAAC) and introducing the covariance discriminant (CD) algorithm, in which a bias-adjustment term, which has the function to automatically adjust the errors caused by the bias due to the imbalance of training data, had been incorporated. Rigorous cross-validations indicated that the new predictor remarkably outperformed the existing state-of-the-art prediction method for the same purpose. AVAILABILITY AND IMPLEMENTATION: For the convenience of most experimental scientists, a user-friendly web-server for pSumo-CD has been established at http://www.jci-bioinfo.cn/pSumo-CD, by which users can easily obtain their desired results without the need to go through the complicated mathematical equations involved. CONTACT: jjia@gordonlifescience.org, xxiao@gordonlifescience.org or kcchou@gordonlifescience.orgSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27354697 TI - Cyclo-lib: a database of computational molecular dynamics simulations of cyclodextrins. AB - MOTIVATION: Cyclodextrins (CDs) are amongst the most versatile/multi-functional molecules used in molecular research and chemical applications. They are natural cyclic oligosaccharides typically employed to encapsulate hydrophobic groups in their central cavity. This allows solubilizing, protecting or reducing the toxicity of a large variety of different molecules including drugs, dyes and surfactant agents. In spite of their great potential, atomic level information of these molecules, which is key for their function, is really scarce. Computational Molecular Dynamics (MD) simulations have the potential to efficiently fill this gap, providing structural-dynamic information at atomic level in time scales ranging from ps to MUs. RESULTS: Cyclo-lib is a database with a publicly accessible web-interface containing structural and dynamic analysis obtained from computational MD simulation trajectories (250 ns long) of native and modified CDs in explicit water molecules. Cyclo-lib currently includes 70 CDs typically employed for fundamental and industrial research. Tools for comparative analysis between different CDs, as well as to restrict the analysis to specific time segments within the trajectories are also available. Cyclo-lib provides atomic resolution information aimed to complement experimental results performed with the same molecules. AVAILABILITY AND IMPLEMENTATION: The database is freely available under http://cyclo-lib.mduse.com/ CONTACT: Angel.Pineiro@usc.es. PMID- 27354698 TI - Structural distinctions of fast and slow bacterial luciferases revealed by phylogenetic analysis. AB - MOTIVATION: Bacterial luciferases are heterodimeric enzymes that catalyze a chemical reaction, so called bioluminescence, which causes light emission in bacteria. Bioluminescence is vastly used as a reporter system in research tools and commercial developments. However, the details of the mechanisms that stabilize and transform the reaction intermediates as well as differences in the enzymatic kinetics amongst different bacterial luciferases remain to be elucidated. RESULTS: Amino acid sequences alignments for 21 bacterial luciferases (both alpha- and beta-subunits) were analyzed. For alpha-subunit, containing the enzyme active center, 48 polymorphic amino acid positions were identified. According to them, the sequences fell into two distinct groups known as slow and fast based on the decay rate of the bioluminescence reaction. The differences in the enzyme active site induced by structural polymorphism are analyzed. AVAILABILITY AND IMPLEMENTATION: Three-dimensional models of Photobacterium leiognathi luciferase and Vibrio harveyi luciferase (with reconstructed mobile loop) are freely available at PMDB database: PM0080525 and PM0080526, respectively. CONTACT: adeeva@sfu-kras.ruSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27354699 TI - Conpair: concordance and contamination estimator for matched tumor-normal pairs. AB - MOTIVATION: Sequencing of matched tumor and normal samples is the standard study design for reliable detection of somatic alterations. However, even very low levels of cross-sample contamination significantly impact calling of somatic mutations, because contaminant germline variants can be incorrectly interpreted as somatic. There are currently no sequence-only based methods that reliably estimate contamination levels in tumor samples, which frequently display copy number changes. As a solution, we developed Conpair, a tool for detection of sample swaps and cross-individual contamination in whole-genome and whole-exome tumor-normal sequencing experiments. RESULTS: On a ladder of in silico contaminated samples, we demonstrated that Conpair reliably measures contamination levels as low as 0.1%, even in presence of copy number changes. We also estimated contamination levels in glioblastoma WGS and WXS tumor-normal datasets from TCGA and showed that they strongly correlate with tumor-normal concordance, as well as with the number of germline variants called as somatic by several widely-used somatic callers. AVAILABILITY AND IMPLEMENTATION: The method is available at: https://github.com/nygenome/conpair CONTACT: egrabowska@gmail.com or mczody@nygenome.orgSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27354700 TI - GeneCodeq: quality score compression and improved genotyping using a Bayesian framework. AB - MOTIVATION: The exponential reduction in cost of genome sequencing has resulted in a rapid growth of genomic data. Most of the entropy of short read data lies not in the sequence of read bases themselves but in their Quality Scores-the confidence measurement that each base has been sequenced correctly. Lossless compression methods are now close to their theoretical limits and hence there is a need for lossy methods that further reduce the complexity of these data without impacting downstream analyses. RESULTS: We here propose GeneCodeq, a Bayesian method inspired by coding theory for adjusting quality scores to improve the compressibility of quality scores without adversely impacting genotyping accuracy. Our model leverages a corpus of k-mers to reduce the entropy of the quality scores and thereby the compressibility of these data (in FASTQ or SAM/BAM/CRAM files), resulting in compression ratios that significantly exceeds those of other methods. Our approach can also be combined with existing lossy compression schemes to further reduce entropy and allows the user to specify a reference panel of expected sequence variations to improve the model accuracy. In addition to extensive empirical evaluation, we also derive novel theoretical insights that explain the empirical performance and pitfalls of corpus-based quality score compression schemes in general. Finally, we show that as a positive side effect of compression, the model can lead to improved genotyping accuracy. AVAILABILITY AND IMPLEMENTATION: GeneCodeq is available at: github.com/genecodeq/eval CONTACT: dan@petagene.comSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27354701 TI - CellProfiler Analyst: interactive data exploration, analysis and classification of large biological image sets. AB - : CellProfiler Analyst allows the exploration and visualization of image-based data, together with the classification of complex biological phenotypes, via an interactive user interface designed for biologists and data scientists. CellProfiler Analyst 2.0, completely rewritten in Python, builds on these features and adds enhanced supervised machine learning capabilities (Classifier), as well as visualization tools to overview an experiment (Plate Viewer and Image Gallery). AVAILABILITY AND IMPLEMENTATION: CellProfiler Analyst 2.0 is free and open source, available at http://www.cellprofiler.org and from GitHub (https://github.com/CellProfiler/CellProfiler-Analyst) under the BSD license. It is available as a packaged application for Mac OS X and Microsoft Windows and can be compiled for Linux. We implemented an automatic build process that supports nightly updates and regular release cycles for the software. CONTACT: anne@broadinstitute.orgSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27354702 TI - AutoSite: an automated approach for pseudo-ligands prediction-from ligand-binding sites identification to predicting key ligand atoms. AB - MOTIVATION: The identification of ligand-binding sites from a protein structure facilitates computational drug design and optimization, and protein function assignment. We introduce AutoSite: an efficient software tool for identifying ligand-binding sites and predicting pseudo ligand corresponding to each binding site identified. Binding sites are reported as clusters of 3D points called fills in which every point is labelled as hydrophobic or as hydrogen bond donor or acceptor. From these fills AutoSite derives feature points: a set of putative positions of hydrophobic-, and hydrogen-bond forming ligand atoms. RESULTS: We show that AutoSite identifies ligand-binding sites with higher accuracy than other leading methods, and produces fills that better matches the ligand shape and properties, than the fills obtained with a software program with similar capabilities, AutoLigand In addition, we demonstrate that for the Astex Diverse Set, the feature points identify 79% of hydrophobic ligand atoms, and 81% and 62% of the hydrogen acceptor and donor hydrogen ligand atoms interacting with the receptor, and predict 81.2% of water molecules mediating interactions between ligand and receptor. Finally, we illustrate potential uses of the predicted feature points in the context of lead optimization in drug discovery projects. AVAILABILITY AND IMPLEMENTATION: http://adfr.scripps.edu/AutoDockFR/autosite.html CONTACT: sanner@scripps.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27354703 TI - Evolving specificity of tRNA 3-methyl-cytidine-32 (m3C32) modification: a subset of tRNAsSer requires N6-isopentenylation of A37. AB - Post-transcriptional modifications of anticodon loop (ACL) nucleotides impact tRNA structure, affinity for the ribosome, and decoding activity, and these activities can be fine-tuned by interactions between nucleobases on either side of the anticodon. A recently discovered ACL modification circuit involving positions 32, 34, and 37 is disrupted by a human disease-associated mutation to the gene encoding a tRNA modification enzyme. We used tRNA-HydroSeq (-HySeq) to examine (3)methyl-cytidine-32 (m(3)C32), which is found in yeast only in the ACLs of tRNAs(Ser) and tRNAs(Thr) In contrast to that reported for Saccharomyces cerevisiae in which all m(3)C32 depends on a single gene, TRM140, the m(3)C32 of tRNAs(Ser) and tRNAs(Thr) of the fission yeast S. pombe, are each dependent on one of two related genes, trm140(+) and trm141(+), homologs of which are found in higher eukaryotes. Interestingly, mammals and other vertebrates contain a third homolog and also contain m(3)C at new sites, positions 32 on tRNAs(Arg) and C47:3 in the variable arm of tRNAs(Ser) More significantly, by examining S. pombe mutants deficient for other modifications, we found that m(3)C32 on the three tRNAs(Ser) that contain anticodon base A36, requires N(6)-isopentenyl modification of A37 (i(6)A37). This new C32-A37 ACL circuitry indicates that i(6)A37 is a pre- or corequisite for m(3)C32 on these tRNAs. Examination of the tRNA database suggests that such circuitry may be more expansive than observed here. The results emphasize two contemporary themes, that tRNA modifications are interconnected, and that some specific modifications on tRNAs of the same anticodon identity are species-specific. PMID- 27354704 TI - Structure-function analysis and genetic interactions of the Luc7 subunit of the Saccharomyces cerevisiae U1 snRNP. AB - Luc7 is an essential 261-amino acid protein subunit of the Saccharomyces cerevisiae U1 snRNP. To establish structure-function relations for yeast Luc7, we conducted an in vivo mutational analysis entailing N- and C-terminal truncations and alanine scanning of phylogenetically conserved amino acids, including two putative zinc finger motifs, ZnF1 and ZnF2, and charged amino acids within the ZnF2 module. We identify Luc7-(31-246) as a minimal functional protein and demonstrate that whereas mutations of the CCHH ZnF2 motif are lethal, mutations of the ZnF1 CCCH motif and the charged residues of the ZnF2 modules are not. Though dispensable for vegetative growth in an otherwise wild-type background, the N-terminal 18-amino acid segment of Luc7 plays an important role in U1 snRNP function, evinced by our findings that its deletion (i) impaired the splicing of SUS1 pre-mRNA; (ii) was synthetically lethal absent other U1 snRNP constituents (Mud1, Nam8, the TMG cap, the C terminus of Snp1), absent the Mud2 subunit of the Msl5*Mud2 branchpoint binding complex, and when the m(7)G cap-binding site of Cbc2 was debilitated; and (iii) bypassed the need for the essential DEAD-box ATPase Prp28. Similar phenotypes were noted for ZnF1 mutations C45A, C53A, and C68A and ZnF2 domain mutations D214A, R215A, R216A, and D219A These findings highlight the contributions of the Luc7 N-terminal peptide, the ZnF1 motif, and the ZnF2 module in stabilizing the interactions of the U1 snRNP with the pre-mRNA 5' splice site and promoting the splicing of a yeast pre-mRNA, SUS1, that has a nonconsensus 5' splice site. PMID- 27354705 TI - The S. pombe mRNA decapping complex recruits cofactors and an Edc1-like activator through a single dynamic surface. AB - The removal of the 5' 7-methylguanosine mRNA cap structure (decapping) is a central step in the 5'-3' mRNA degradation pathway and is performed by the Dcp1:Dcp2 decapping complex. The activity of this complex is tightly regulated to prevent premature degradation of the transcript. Here, we establish that the aromatic groove of the EVH1 domain of Schizosaccharomyces pombe Dcp1 can interact with proline-rich sequences in the exonuclease Xrn1, the scaffolding protein Pat1, the helicase Dhh1, and the C-terminal disordered region of Dcp2. We show that this region of Dcp1 can also recruit a previously unidentified enhancer of decapping protein (Edc1) and solved the crystal structure of the complex. NMR relaxation dispersion experiments reveal that the Dcp1 binding site can adopt multiple conformations, thus providing the plasticity that is required to accommodate different ligands. We show that the activator Edc1 makes additional contacts with the regulatory domain of Dcp2 and that an activation motif in Edc1 increases the RNA affinity of Dcp1:Dcp2. Our data support a model where Edc1 stabilizes the RNA in the active site, which results in enhanced decapping rates. In summary, we show that multiple decapping factors, including the Dcp2 C terminal region, compete with Edc1 for Dcp1 binding. Our data thus reveal a network of interactions that can fine-tune the catalytic activity of the decapping complex. PMID- 27354706 TI - Monilophyte mitochondrial rps1 genes carry a unique group II intron that likely originated from an ancient paralog in rpl2. AB - Intron patterns in plant mitochondrial genomes differ significantly between the major land plant clades. We here report on a new, clade-specific group II intron in the rps1 gene of monilophytes (ferns). This intron, rps1i25g2, is strikingly similar to rpl2i846g2 previously identified in the mitochondrial rpl2 gene of seed plants, ferns, and the lycophyte Phlegmariurus squarrosus Although mitochondrial ribosomal protein genes are frequently subject to endosymbiotic gene transfer among plants, we could retrieve the mitochondrial rps1 gene in a taxonomically wide sampling of 44 monilophyte taxa including basal lineages such as the Ophioglossales, Psilotales, and Marattiales with the only exception being the Equisetales (horsetails). Introns rps1i25g2 and rpl2i846g2 were likewise consistently present with only two exceptions: Intron rps1i25g2 is lost in the genus Ophioglossum and intron rpl2i846g2 is lost in Equisetum bogotense Both intron sequences are moderately affected by RNA editing. The unprecedented primary and secondary structure similarity of rps1i25g2 and rpl2i846g2 suggests an ancient retrotransposition event copying rpl2i846g2 into rps1, for which we suggest a model. Our phylogenetic analysis adding the new rps1 locus to a previous data set is fully congruent with recent insights on monilophyte phylogeny and further supports a sister relationship of Gleicheniales and Hymenophyllales. PMID- 27354708 TI - Safety Evaluation of CNS Administered Biologics-Study Design, Data Interpretation, and Translation to the Clinic. AB - Many central nervous system (CNS) diseases are inadequately treated by systemically administered therapies due to the blood brain barrier (BBB), which prevents achieving adequate drug concentrations at sites of action. Due to the increasing prevalence of neurodegenerative diseases and the inability of most systemically administered therapies to cross the BBB, direct CNS delivery will likely play an increasing role in treatment. Administration of large molecules, cells, viral vectors, oligonucleotides, and other novel therapies directly to the CNS via the subarachnoid space, ventricular system, or parenchyma overcomes this obstacle. Clinical experience with direct CNS administration of small molecule therapies suggests that this approach may be efficacious for the treatment of neurodegenerative disorders using biological therapies. Risks of administration into the brain tissue or cerebrospinal fluid include local damage from implantation of the delivery system and/or administration of the therapeutic and reactions affecting the CNS. Preclinical safety studies on CNS administered compounds must differentiate between the effects of the test article, the delivery device, and/or the vehicle, and assess exacerbations of reactions due to combinations of effects. Animal models characterized for safety assessment of CNS administered therapeutics have enabled human trials, but interpretation can be challenging. This manuscript outlines the challenges of preclinical intrathecal/intracerebroventricular/intraparenchymal studies, evaluation of results, considerations for special endpoints, and translation of preclinical findings to enable first-in-human trials. Recommendations will be made based on the authors' collective experience with conducting these studies to enable clinical development of CNS-administered biologics. PMID- 27354709 TI - Nonparametric binary instrumental variable analysis of competing risks data. AB - In both observational studies and randomized trials with noncompliance, unmeasured confounding may exist which may bias treatment effect estimates. Instrumental variables (IV) are a popular technique for addressing such confounding, enabling consistent estimation of causal effects. This paper proposes nonparametric IV estimators for censored time to event data that may be subject to competing risks. A simple, plug-in estimator is introduced using nonparametric estimators of the cumulative incidence function, with confidence intervals derived using asymptotic theory. To provide an overall test of the treatment effect, an integrated weighted difference statistic is suggested, which is applicable to data with and without competing risks. Simulation studies demonstrate that the methods perform well with realistic samples sizes. The methods are applied to assess the effect of infant or maternal antiretroviral therapy on transmission of HIV from mother to child via breastfeeding using data from a large, recently completed randomized trial in Malawi where noncompliance with assigned treatment may confound treatment effect estimates. PMID- 27354711 TI - Muscle shortening velocity depends on tissue inertia and level of activation during submaximal contractions. AB - In order to perform external work, muscles must do additional internal work to deform their tissue, and in particular, to overcome the inertia due to their internal mass. However, the contribution of the internal mass within a muscle to the mechanical output of that muscle has only rarely been studied. Here, we use a dynamic, multi-element Hill-type muscle model to examine the effects of the inertial mass within muscle on its contractile performance. We find that the maximum strain-rate of muscle is slower for lower activations and larger muscle sizes. As muscle size increases, the ability of the muscle to overcome its inertial load will decrease, as muscle tension is proportional to cross-sectional area and inertial load is proportional to mass. Thus, muscles that are larger in size will have a higher inertial cost to contraction. Similarly, when muscle size and inertial load are held constant, decreasing muscle activation will increase inertial cost to contraction by reducing muscle tension. These results show that inertial loads within muscle contribute to a slowing of muscle contractile velocities (strain-rates), particularly at the submaximal activations that are typical during animal locomotion. PMID- 27354710 TI - Semiparametric density ratio modeling of survival data from a prevalent cohort. AB - In this article, we consider methods for assessing covariate effects on survival outcome in the target population when data are collected under prevalent sampling. We investigate a flexible semiparametric density ratio model without the constraints of the constant disease incidence rate and discrete covariates as required in Shen and others 2012. For inference, we introduce two likelihood approaches with distinct computational algorithms. We first develop a full likelihood approach to obtain the most efficient estimators by an iterative algorithm. Under the density ratio model, we exploit the invariance property of uncensored failure times from the prevalent cohort and also propose a computationally convenient estimation procedure that uses a conditional pairwise likelihood. The empirical performance and efficiency of the two approaches are evaluated through simulation studies. The proposed methods are applied to the Surveillance, Epidemiology, and End Results Medicare linked data for women diagnosed with stage IV breast cancer. PMID- 27354712 TI - Inbreeding removes sex differences in lifespan in a population of Drosophila melanogaster. AB - Sex differences in ageing rates and lifespan are common in nature, and an enduring puzzle for evolutionary biology. One possibility is that sex-specific mortality rates may result from recessive deleterious alleles in 'unguarded' heterogametic X or Z sex chromosomes (the unguarded X hypothesis). Empirical evidence for this is, however, limited. Here, we test a fundamental prediction of the unguarded X hypothesis in Drosophila melanogaster, namely that inbreeding shortens lifespan more in females (the homogametic sex in Drosophila) than in males. To test for additional sex-specific social effects, we studied the lifespan of males and females kept in isolation, in related same-sex groups, and in unrelated same-sex groups. As expected, outbred females outlived outbred males and inbreeding shortened lifespan. However, inbreeding-mediated reductions in lifespan were stronger for females, such that lifespan was similar in inbred females and males. We also show that the social environment, independent of inbreeding, affected male, but not female lifespan. In conjunction with recent studies, the present results suggest that asymmetric inheritance mechanisms may play an important role in the evolution of sex-specific lifespan and that social effects must be considered explicitly when studying these fundamental patterns. PMID- 27354713 TI - Stress response, gut microbial diversity and sexual signals correlate with social interactions. AB - Theory predicts that social interactions are dynamically linked to phenotype. Yet because social interactions are difficult to quantify, little is known about the precise details on how interactivity is linked to phenotype. Here, we deployed proximity loggers on North American barn swallows (Hirundo rustica erythrogaster) to examine intercorrelations among social interactions, morphology and features of the phenotype that are sensitive to the social context: stress-induced corticosterone (CORT) and gut microbial diversity. We analysed relationships at two spatial scales of interaction: (i) body contact and (ii) social interactions occurring between 0.1 and 5 m. Network analysis revealed that relationships between social interactions, morphology, CORT and gut microbial diversity varied depending on the sexes of the individuals interacting and the spatial scale of interaction proximity. We found evidence that body contact interactions were related to diversity of socially transmitted microbes and that looser social interactions were related to signalling traits and CORT. PMID- 27354714 TI - Spatial distribution of xylem embolisms in the stems of Pinus thunbergii at the threshold of fatal drought stress. AB - Although previous studies have suggested that branch dieback and whole-plant death due to drought stress occur at 50-88% loss of stem hydraulic conductivity (P50 and P88, respectively), the dynamics of catastrophic failure in the water conducting pathways in whole plants subjected to drought remain poorly understood. We examined the dynamics of drought stress tolerance in 3-year-old Japanese black pine (Pinus thunbergii Parl.). We nondestructively monitored (i) the spatial distribution of drought-induced embolisms in the stem at greater than P50 and (ii) recovery from embolisms following rehydration. Stem water distributions were visualized by cryo-scanning electron microscopy. The percentages of both embolized area and loss of hydraulic conductivity showed similar patterns of increase, although the water loss in xylem increased markedly at -5.0 MPa or less. One seedling that had reached 72% loss of the water conducting area survived and the xylem water potential recovered to -0.3 MPa. We concluded that Japanese black pines may need to maintain water-filled tracheids within earlywood of the current-year xylem under natural conditions to avoid disconnection of water movement between the stem and the tops of branches. It is necessary to determine the spatial distribution of embolisms around the point of the lethal threshold to gain an improved understanding of plant survival under conditions of drought. PMID- 27354715 TI - Bone micro-architectural analysis of mandible and tibia in ovariectomised rats: A quantitative structural comparison between undecalcified histological sections and micro-CT. AB - OBJECTIVES: This study aims to evaluate if micro-CT can work as a method for the 3D assessment and analysis of cancellous bone by comparing micro-CT with undecalcified histological sections in OVX rats. METHODS: The mandible and tibia of sham, ovariectomised (OVX) and zoledronate-injected ovariectomised (OVX-ZOL) rats were assessed morphometrically. Specimens were scanned by micro-CT. Undecalcified histological sections were manufactured from the specimen scanned by micro-CT and stained with haematoxylin and eosin. Bivariate linear regressions and one-way analysis of variance were undertaken for statistics using SPSS 16.0.1 software. RESULTS: There were highly significant correlations between undecalcified histological sections and micro-CT for all parameters (bone volume density (BV/TV), bone surface density (BS/BV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp))in the mandible and tibia. Bone histomorphometric parameters analysed by both methods exhibited significant differences among sham, OVX, and OVX-ZOL groups. There were significant correlations between mandible and tibia in BV/TV, BS/BV, and Tb.Sp. CONCLUSIONS: Micro-CT is a complementary tool to histological sections in basic research that could improve our understanding of bone histomorphometry. The mandible can be used as an effective site to assess bone morphometry of OVX or metabolic bone disease rat models.Cite this article: H. Liu, W. Li, Y. S. Liu, Y. S. Zhou. Bone micro-architectural analysis of mandible and tibia in ovariectomised rats: A quantitative structural comparison between undecalcified histological sections and micro-CT. Bone Joint Res 2016;5:253-262. PMID- 27354716 TI - Retractions in orthopaedic research: A systematic review. AB - OBJECTIVES: Despite the fact that research fraud and misconduct are under scrutiny in the field of orthopaedic research, little systematic work has been done to uncover and characterise the underlying reasons for academic retractions in this field. The purpose of this study was to determine the rate of retractions and identify the reasons for retracted publications in the orthopaedic literature. METHODS: Two reviewers independently searched MEDLINE, EMBASE, and the Cochrane Library (1995 to current) using MeSH keyword headings and the 'retracted' filter. We also searched an independent website that reports and archives retracted scientific publications (www.retractionwatch.com). Two reviewers independently extracted data including reason for retraction, study type, journal impact factor, and country of origin. RESULTS: One hundred and ten retracted studies were included for data extraction. The retracted studies were published in journals with impact factors ranging from 0.000 (discontinued journals) to 13.262. In the 20-year search window, only 25 papers were retracted in the first ten years, with the remaining 85 papers retracted in the most recent decade. The most common reasons for retraction were fraudulent data (29), plagiarism (25) and duplicate publication (20). Retracted articles have been cited up to 165 times (median 6; interquartile range 2 to 19). CONCLUSION: The rate of retractions in the orthopaedic literature is increasing, with the majority of retractions attributed to academic misconduct and fraud. Orthopaedic retractions originate from numerous journals and countries, indicating that misconduct issues are widespread. The results of this study highlight the need to address academic integrity when training the next generation of orthopaedic investigators.Cite this article: J. Yan, A. MacDonald, L-P. Baisi, N. Evaniew, M. Bhandari, M. Ghert. Retractions in orthopaedic research: A systematic review. Bone Joint Res 2016;5:263-268. DOI: 10.1302/2046-3758.56.BJR-2016-0047. PMID- 27354717 TI - Improving the accuracy of sports medicine surveillance: when is a subsequent event a new injury? AB - The recent increased use of injury and illness surveillance programmes has the potential to greatly advance our knowledge about risk factors and treatment effectiveness. Maximising this potential requires that data be entered in a format that can be interpreted and analysed. One remaining challenge concerns whether and when an increase in symptoms should be documented within an existing injury record (eg, exacerbation) versus a new injury record. In this review, we address this challenge using the principles of the multistate framework for the analysis of subsequent injury in sport (M-FASIS). In brief, we argue that a new injury record should be documented whenever there is an increase in symptoms due to activity-related exposures that is beyond the normal day-to-day symptom fluctuations, regardless of whether the athlete was in a 'healthy state' immediately before the event. We illustrate the concepts with concrete examples of shoulder osteoarthritis, ankle sprains and ACL tears. PMID- 27354718 TI - The Copenhagen Consensus Conference 2016: children, youth, and physical activity in schools and during leisure time. AB - From 4 to 7 April 2016, 24 researchers from 8 countries and from a variety of academic disciplines gathered in Snekkersten, Denmark, to reach evidence-based consensus about physical activity in children and youth, that is, individuals between 6 and 18 years. Physical activity is an overarching term that consists of many structured and unstructured forms within school and out-of-school-time contexts, including organised sport, physical education, outdoor recreation, motor skill development programmes, recess, and active transportation such as biking and walking. This consensus statement presents the accord on the effects of physical activity on children's and youth's fitness, health, cognitive functioning, engagement, motivation, psychological well-being and social inclusion, as well as presenting educational and physical activity implementation strategies. The consensus was obtained through an iterative process that began with presentation of the state-of-the art in each domain followed by plenary and group discussions. Ultimately, Consensus Conference participants reached agreement on the 21-item consensus statement. PMID- 27354719 TI - Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma. AB - For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter, open-label phase 1/2 trial, we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment for elderly patients with MCL. Patients >65 years with untreated MCL, stages II-IV were eligible for inclusion. Primary end points were maximally tolerable dose (MTD) of LEN and progression-free survival (PFS). Patients received 6 cycles every four weeks of L-B-R (L D1-14, B 90 mg/m2 IV, days 1-2 and R 375 mg/m2 IV, day 1) followed by single LEN (days 1-21, every four weeks, cycles 7-13). Fifty-one patients (median age 71 years) were enrolled from 2009 to 2013. In phase 1, the MTD of LEN was defined as 10 mg in cycles 2 through 6, and omitted in cycle 1. After 6 cycles, the complete remission rate (CRR) was 64%, and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3-year overall survival was 73%. Infection was the most common nonhematologic grade 3 to 5 event and occurred in 21 (42%) patients. Opportunistic infections occurred in 3 patients: 2 Pneumocystis carinii pneumonia and 1 cytomegalovirus retinitis. Second primary malignancies (SPM) were observed in 8 patients (16%). LEN could safely be combined with R-B when added from the second cycle in patients with MCL, and was associated with a high rate of CR and molecular remission. However, we observed a high degree of severe infections and an unexpected high number of SPMs, which may limit its use. This trial is registered at www.Clinicaltrials.gov as #NCT00963534. PMID- 27354720 TI - Maintenance therapy in acute myeloid leukemia: an evidence-based review of randomized trials. PMID- 27354721 TI - The role of leukocytes in thrombosis. AB - In recent years, the traditional view of the hemostatic system as being regulated by a coagulation factor cascade coupled with platelet activation has been increasingly challenged by new evidence that activation of the immune system strongly influences blood coagulation and pathological thrombus formation. Leukocytes can be induced to express tissue factor and release proinflammatory and procoagulant molecules such as granular enzymes, cytokines, and damage associated molecular patterns. These mediators can influence all aspects of thrombus formation, including platelet activation and adhesion, and activation of the intrinsic and extrinsic coagulation pathways. Leukocyte-released procoagulant mediators increase systemic thrombogenicity, and leukocytes are actively recruited to the site of thrombus formation through interactions with platelets and endothelial cell adhesion molecules. Additionally, phagocytic leukocytes are involved in fibrinolysis and thrombus resolution, and can regulate clearance of platelets and coagulation factors. Dysregulated activation of leukocyte innate immune functions thus plays a role in pathological thrombus formation. Modulation of the interactions between leukocytes or leukocyte-derived procoagulant materials and the traditional hemostatic system is an attractive target for the development of novel antithrombotic strategies. PMID- 27354722 TI - Characteristics, outcome, and response to therapy of multirefractory chronic immune thrombocytopenia. AB - Refractory immune thrombocytopenia (ITP) was previously defined as lack of a minimum response to splenectomy and the requirement for long-term treatment to reduce the risk of significant bleeding events. In this multicenter study, we included 37 patients with multirefractory ITP, defined as no response to splenectomy, rituximab, romiplostim, and eltrombopag. As compared with a historical cohort of 183 ITP patients, matched on the calendar year of ITP diagnosis with a 5:1 ratio, patients with multirefractory ITP were more likely to have secondary ITP (odds ratio [OR], 4.84; 95% confidence interval [CI], 1.31 17.86; P = .018) and monoclonal gammopathy of undetermined significance (OR, 5.94; 95% CI, 1.08-32.48; P = .04). The median duration of ITP before being recognized as multirefractory was 78 months (range, 6-450). The patients showed failure of a median of 10.5 prior treatment lines for ITP (range, 6-15). At the end of follow-up (median, 84 months; range, 12-455), only 1/14 patients achieved response with immunosuppressant therapy alone. By contrast, 7/10 patients achieved response with a combination of immunosuppressant therapy and thrombopoietin-receptor agonists that lasted for a median of 15 months (range, 6 32). Throughout the course of ITP, 5/37 patients died, 3 with ITP (bleeding, n = 2; sepsis n = 1); 15 (40%) had at least 1 bacterial infection and 9 (24%) at least 1 episode of thrombosis. In conclusion, multirefractory ITP was associated with high morbidity and mortality. Combining an immunosuppressant therapy with thrombopoietin-receptor agonists may be a good strategy for management for these patients with severe disease. PMID- 27354724 TI - New bone turnover measure is more accurate predictor of postmenopausal bone loss. PMID- 27354723 TI - Disseminated intravascular coagulation at diagnosis is a strong predictor for thrombosis in acute myeloid leukemia. AB - Venous thromboembolism is a common complication in patients with cancer, but only limited data are available in acute myeloid leukemia (AML). In a prospective study in a cohort of 272 adult patients (aged 18-65) and an independent validation cohort of 132 elderly adults (aged >60) with newly diagnosed AML, we assessed markers of disseminated intravascular coagulation (DIC) (fibrinogen, D dimer, alpha-2-antiplasmin, antitrombin, prothrombin time, and platelet count) and the DIC score according the International Society of Thrombosis and Haemostasis and their associations with the occurrence of venous and arterial thrombosis during follow-up. The prevalence of thrombosis was 8.7% (4.7% venous, 4.0% arterial) in the younger adults over a median follow-up of 478 days and 10.4% (4.4% venous, 5.9% arterial) in elderly patients. Most thrombotic events (66%) occurred before the start of the second course of chemotherapy. The calculated DIC score significantly predicted venous and arterial thrombosis with a hazard ratio (HR) for a high DIC score (>=5) of 4.79 (1.71-13.45). These results were confirmed in the validation cohort of elderly patients with AML (HR 11.08 [3.23-38.06]). Among all DIC parameters, D-dimer levels are most predictive for thrombosis with an HR of 12.3 (3.39-42.64) in the first cohort and an HR of 7.82 (1.95-31.38) in validation cohort for a D-dimer >4 mg/L vs <=4 mg/L. It is concluded that venous and arterial thrombosis may develop in ~10% of AML patients treated with intensive chemotherapy, which to a large extent can be predicted by the presence of DIC at time of AML diagnosis. PMID- 27354725 TI - UK stands by nasal flu vaccine for children as US doctors are told to stop using it. PMID- 27354726 TI - Superhydrophobicity of the gecko toe pad: biological optimization versus laboratory maximization. AB - While many gecko-inspired hierarchically structured surfaces perform as well as or better than the natural adhesive system, these designs often fail to function across a variety of contexts. For example, the gecko can adhere to rough, wet and dirty surfaces; however, most synthetic mimics cannot maintain function when faced with a similar situation. The solution to this problem lies in a more thorough investigation of the natural system. Here, we review the adhesive system of the gecko toe pad, as well as the far less-well-studied anti-adhesive system that results from the chemistry and structure of the toe pad (superhydrophobicity). This paradoxical relationship serves as motivation to study functional optimization at the system level. As an example, we experimentally investigate the role of surface lipids in adhesion and anti adhesion, and find a clear performance trade-off related to shear adhesion in air on a hydrophilic surface. This represents the first direct investigation of the role of surface lipids in gecko adhesion and anti-adhesion, and supports the argument that a system-level approach is necessary to elucidate optimization in biological systems. Without such an approach, bioinspired designs will be limited in functionality and context, especially compared to the natural systems they mimic.This article is part of the themed issue 'Bioinspired hierarchically structured surfaces for green science'. PMID- 27354727 TI - Bioarchitecture: bioinspired art and architecture--a perspective. AB - Art and architecture can be an obvious choice to pair with science though historically this has not always been the case. This paper is an attempt to interact across disciplines, define a new genre, bioarchitecture, and present opportunities for further research, collaboration and professional cooperation. Biomimetics, or the copying of living nature, is a field that is highly interdisciplinary, involving the understanding of biological functions, structures and principles of various objects found in nature by scientists. Biomimetics can lead to biologically inspired design, adaptation or derivation from living nature. As applied to engineering, bioinspiration is a more appropriate term, involving interpretation, rather than direct copying. Art involves the creation of discrete visual objects intended by their creators to be appreciated by others. Architecture is a design practice that makes a theoretical argument and contributes to the discourse of the discipline. Bioarchitecture is a blending of art/architecture and biomimetics/bioinspiration, and incorporates a bioinspired design from the outset in all parts of the work at all scales. Herein, we examine various attempts to date of art and architecture to incorporate bioinspired design into their practice, and provide an outlook and provocation to encourage collaboration among scientists and designers, with the aim of achieving bioarchitecture.This article is part of the themed issue 'Bioinspired hierarchically structured surfaces for green science'. PMID- 27354728 TI - Why re-entrant surface topography is needed for robust oleophobicity. AB - Surface patterns affect wetting properties of solid materials allowing manipulation of the phase state of an adjacent fluid. The best known example of this effect is the superhydrophobic composite (Cassie-Baxter) interface with vapour/air pockets between the solid and liquid. Mathematically, the effect of surface micropatterns can be studied by an averaging technique similarly to the method of separation of motions in dynamics. However, averaged parameters are insufficient for robust superhydrophobic and superoleophobic surfaces because additional topography features are important: hierarchical organization and re entrant roughness. The latter is crucial for the oleophobicity because it enhances the stability of a composite interface. The re-entrant topography can be achieved by various methods. Understanding the role of re-entrant surface topography gives us new insights on the multitude of wetting scenarios beyond the standard Wenzel and Cassie-Baxter models.This article is part of the themed issue 'Bioinspired hierarchically structured surfaces for green science'. PMID- 27354729 TI - Nature has gone through evolution over the 3.8 billion years. Introduction. PMID- 27354730 TI - Durable superoleophobic polypropylene surfaces. AB - Polypropylene (PP) is a popular plastic material used in consumer packaging. It would be desirable if such plastic containers were liquid repellent and not so easily fouled by their contents. Existing examples of superoleophobic surfaces typically rely on poorly adhered coatings or delicate surface structures, resulting in poor mechanical durability. Here, we report a facile method for creating superoleophobic PP surfaces via incorporation of nanoparticles (NPs) into the polymer surface. A solvent-NP-PP mixture was spin coated at high temperature to achieve the necessary roughness. Such surfaces were further functionalized with fluorosilane to result in a durable, super-repellent surface. They were also found to exhibit some repellency towards shampoos. This method of incorporating NPs into polymer surfaces could also prove useful in improving the anti-bacterial, mechanical and liquid-repellent properties of plastic devices.This article is part of the themed issue 'Bioinspired hierarchically structured surfaces for green science'. PMID- 27354731 TI - Bioinspired surfaces for turbulent drag reduction. AB - In this review, we discuss how superhydrophobic surfaces (SHSs) can provide friction drag reduction in turbulent flow. Whereas biomimetic SHSs are known to reduce drag in laminar flow, turbulence adds many new challenges. We first provide an overview on designing SHSs, and how these surfaces can cause slip in the laminar regime. We then discuss recent studies evaluating drag on SHSs in turbulent flow, both computationally and experimentally. The effects of streamwise and spanwise slip for canonical, structured surfaces are well characterized by direct numerical simulations, and several experimental studies have validated these results. However, the complex and hierarchical textures of scalable SHSs that can be applied over large areas generate additional complications. Many studies on such surfaces have measured no drag reduction, or even a drag increase in turbulent flow. We discuss how surface wettability, roughness effects and some newly found scaling laws can help explain these varied results. Overall, we discuss how, to effectively reduce drag in turbulent flow, an SHS should have: preferentially streamwise-aligned features to enhance favourable slip, a capillary resistance of the order of megapascals, and a roughness no larger than 0.5, when non-dimensionalized by the viscous length scale.This article is part of the themed issue 'Bioinspired hierarchically structured surfaces for green science'. PMID- 27354732 TI - Bioinspired materials for water supply and management: water collection, water purification and separation of water from oil. AB - Access to a safe supply of water is a human right. However, with growing populations, global warming and contamination due to human activity, it is one that is increasingly under threat. It is hoped that nature can inspire the creation of materials to aid in the supply and management of water, from water collection and purification to water source clean-up and rehabilitation from oil contamination. Many species thrive in even the driest places, with some surviving on water harvested from fog. By studying these species, new materials can be developed to provide a source of fresh water from fog for communities across the globe. The vast majority of water on the Earth is in the oceans. However, current desalination processes are energy-intensive. Systems in our own bodies have evolved to transport water efficiently while blocking other molecules and ions. Inspiration can be taken from such to improve the efficiency of desalination and help purify water containing other contaminants. Finally, oil contamination of water from spills or the fracking technique can be a devastating environmental disaster. By studying how natural surfaces interact with liquids, new techniques can be developed to clean up oil spills and further protect our most precious resource.This article is part of the themed issue 'Bioinspired hierarchically structured surfaces for green science'. PMID- 27354733 TI - Vibrations and spatial patterns in biomimetic surfaces: using the shark-skin effect to control blood clotting. AB - We study the effect of small-amplitude fast vibrations and small-amplitude spatial patterns on various systems involving wetting and liquid flow, such as superhydrophobic surfaces, membranes and flow pipes. First, we introduce a mathematical method of averaging the effect of small spatial and temporal patterns and substituting them with an effective force. Such an effective force can change the equilibrium state of a system as well as a phase state, leading to surface texture-induced and vibration-induced phase control. Vibration and patterns can effectively jam holes in vessels with liquid, separate multi-phase flow, change membrane properties, result in propulsion and locomotion and lead to many other multi-scale, nonlinear effects including the shark-skin effect. We discuss the application of such effects to blood flow for novel biomedical 'haemophobic' applications which can prevent blood clotting and thrombosis by controlling the surface pattern at a wall of a vessel (e.g. a catheter or stent).This article is part of the themed issue 'Bioinspired hierarchically structured surfaces for green science'. PMID- 27354734 TI - Discovery of riblets in a bird beak (Rynchops) for low fluid drag. AB - Riblet structures found on fast-swimming shark scales, such as those found on a mako shark, have been shown to reduce fluid drag. In previous experimental and modelling studies, riblets have been shown to provide drag reduction by lifting vortices formed in turbulent flow, decreasing overall shear stresses. Skimmer birds (Rynchops) are the only birds to catch fish in flight by flying just above the water surface with a submerged beak to fish for food. Because they need to quickly catch prey, reducing drag on their beak is advantageous. For the first time, riblet structures found on the beak of the skimmer bird have been studied experimentally and computationally for low fluid drag properties. In this study, skimmer replicas were studied for drag reduction through pressure drop in closed channel, turbulent water flow. Pressure drop measurements are compared for black and yellow skimmer beaks in two configurations, and mako shark skin. In addition, two configurations of skimmer beak were modelled to compare drag properties and vortex structures. Results are discussed, and a conceptual model is presented to explain a possible drag reduction mechanism in skimmers.This article is part of the themed issue 'Bioinspired hierarchically structured surfaces for green science'. PMID- 27354735 TI - Hierarchical structures of cactus spines that aid in the directional movement of dew droplets. AB - Three species of cactus whose spines act as dew harvesters were chosen for this study: Copiapoa cinerea var. haseltoniana, Mammillaria columbiana subsp. yucatanensis and Parodia mammulosa and compared with Ferocactus wislizenii whose spines do not perform as dew harvesters. Time-lapse snapshots of C. cinerea showed movement of dew droplets from spine tips to their base, even against gravity. Spines emanating from one of the areoles of C. cinerea were submerged in water laced with fluorescent nanoparticles and this particular areole with its spines and a small area of stem was removed and imaged. These images clearly showed that fluorescent water had moved into the stem of the plant. Lines of vascular bundles radiating inwards from the surface areoles (from where the spines emanate) to the core of the stem were detected using magnetic resonance imaging, with the exception of F. wislizenii that does not harvest dew on its spines. Spine microstructures were examined using SEM images and surface roughness measurements (Ra and Rz) taken of the spines of C. cinerea It was found that a roughness gradient created by tapered microgrooves existed that could potentially direct surface water from a spine tip to its base.This article is part of the themed issue 'Bioinspired hierarchically structured surfaces for green science'. PMID- 27354738 TI - BMA meeting: Early dementia diagnosis is pointless without support services. PMID- 27354737 TI - Influence of surface structure and chemistry on water droplet splashing. AB - Water droplet splashing and aerosolization play a role in human hygiene and health systems as well as in crop culturing. Prevention or reduction of splashing can prevent transmission of diseases between animals and plants and keep technical systems such as pipe or bottling systems free of contamination. This study demonstrates to what extent the surface chemistry and structures influence the water droplet splashing behaviour. Smooth surfaces and structured replicas of Calathea zebrina (Sims) Lindl. leaves were produced. Modification of their wettability was done by coating with hydrophobizing and hydrophilizing agents. Their wetting was characterized by contact angle measurement and splashing behaviour was observed with a high-speed video camera. Hydrophobic and superhydrophilic surfaces generally showed fewer tendencies to splash than hydrophobic ones. Structuring amplified the underlying behaviour of the surface chemistries, increasing hydrophobic surfaces' tendency to splash and decreasing splash on hydrophilic surfaces by quickly transporting water off the impact point by capillary forces. The non-porous surface structures found in C. zebrina could easily be applied to technical products such as plastic foils or mats and coated with hydrophilizing agents to suppress splash in areas of increased hygiene requirements or wherever pooling of liquids is not desirable.This article is part of the themed issue 'Bioinspired hierarchically structured surfaces for green science'. PMID- 27354736 TI - Superhydrophobic hierarchically structured surfaces in biology: evolution, structural principles and biomimetic applications. AB - A comprehensive survey of the construction principles and occurrences of superhydrophobic surfaces in plants, animals and other organisms is provided and is based on our own scanning electron microscopic examinations of almost 20 000 different species and the existing literature. Properties such as self-cleaning (lotus effect), fluid drag reduction (Salvinia effect) and the introduction of new functions (air layers as sensory systems) are described and biomimetic applications are discussed: self-cleaning is established, drag reduction becomes increasingly important, and novel air-retaining grid technology is introduced. Surprisingly, no evidence for lasting superhydrophobicity in non-biological surfaces exists (except technical materials). Phylogenetic trees indicate that superhydrophobicity evolved as a consequence of the conquest of land about 450 million years ago and may be a key innovation in the evolution of terrestrial life. The approximate 10 million extant species exhibit a stunning diversity of materials and structures, many of which are formed by self-assembly, and are solely based on a limited number of molecules. A short historical survey shows that bionics (today often called biomimetics) dates back more than 100 years. Statistical data illustrate that the interest in biomimetic surfaces is much younger still. Superhydrophobicity caught the attention of scientists only after the extreme superhydrophobicity of lotus leaves was published in 1997. Regrettably, parabionic products play an increasing role in marketing.This article is part of the themed issue 'Bioinspired hierarchically structured surfaces for green science'. PMID- 27354740 TI - Perfectionism: A Stumbling Block to Effective Leadership? (Every Pharmacist Must Be a Leader). PMID- 27354741 TI - Increasing Hospital Pharmacist Clinical Competence in Intensive Pharmacotherapeutics Using a Novel Pharmacist Clinical Educational Program. PMID- 27354742 TI - Selected Medication Safety Risks to Manage in 2016-Part II; Methylergonovine Errors in Obstetrics. AB - These medication errors have occurred in health care facilities at least once. They will happen again-perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs. Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below. Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site (www.ismp.org), by calling 800-FAIL-SAFE, or via e mail at ismpinfo@ismp.org. ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications. PMID- 27354739 TI - Neural differences in self-perception during illness and after weight-recovery in anorexia nervosa. AB - Anorexia nervosa (AN) is a severe mental illness characterized by problems with self-perception. Whole-brain neural activations in healthy women, women with AN and women in long-term weight recovery following AN were compared using two functional magnetic resonance imaging tasks probing different aspects of self perception. The Social Identity-V2 task involved consideration about oneself and others using socially descriptive adjectives. Both the ill and weight-recovered women with AN engaged medial prefrontal cortex less than healthy women for self relevant cognitions, a potential biological trait difference. Weight-recovered women also activated the inferior frontal gyri and dorsal anterior cingulate more for direct self-evaluations than for reflected self-evaluations, unlike both other groups, suggesting that recovery may include compensatory neural changes related to social perspectives. The Faces task compared viewing oneself to a stranger. Participants with AN showed elevated activity in the bilateral fusiform gyri for self-images, unlike the weight-recovered and healthy women, suggesting cognitive distortions about physical appearance are a state rather than trait problem in this disease. Because both ill and recovered women showed neural differences related to social self-perception, but only recovered women differed when considering social perspectives, these neurocognitive targets may be particularly important for treatment. PMID- 27354743 TI - Acute Generalized Exanthematous Pustulosis Due to Labetalol; Drug Fever and Leukocytosis Caused by Tigecycline; Toxic Hepatitis Induced by Methylprednisolone Intravenous Pulse Dosing; Mitoxantrone-Related Osteonecrosis of the Jaw; Medications with Anticholinergic Effects and Their Implications in the Elderly. AB - The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) Med Watch program (800-FDA-1088). If you have reported an interesting, preventable ADR to Med Watch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's Med Watch program and Temple University School of Pharmacy. ISMP is an FDA Med Watch partner. PMID- 27354744 TI - Carboplatin and Liposomal Doxorubicin for Ovarian Cancer. AB - The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net. PMID- 27354745 TI - Montelukast: Eosinophilic Esophagitis. AB - This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to jgeneral@ku.edu. PMID- 27354747 TI - Comparison of Clevidipine Versus Sodium Nitroprusside for the Treatment of Postoperative Hypertension in Cardiac Surgery Patients. AB - OBJECTIVE: To evaluate the efficacy and safety of clevidipine (CLV) versus sodium nitroprusside (SNP) for the treatment of hypertension (HTN) in postoperative cardiac surgery patients at a community hospital. METHODS: This single-center, retrospective, cohort study included cardiac surgery patients treated with CLV or SNP for postoperative systolic blood pressure (SBP) control. The primary efficacy outcome was defined as the mean number of times the SBP rose above 140 mm Hg. Secondary outcomes included a comparative cost analysis and a safety analysis. RESULTS: Forty patients were included in each arm. Patients who received CLV had a higher incidence of SBP readings greater than 140 mm Hg (p < .05). There were no differences in safety outcomes, number of patients who received as-needed (PRN) antihypertensives, or mean number of PRN antihypertensives required. There were differences in infusion duration (22.4 hours CLV vs 15.6 hours SNP; p = .035), number of infusions dispensed (2.8 CLV vs 1.3 SNP; p = .001), and length of hospital stay (12.33 days CLV vs 7.65 days SNP; p = .013). However, CLV was less expensive based on the AWP cost at the time of review. CONCLUSIONS: Although a difference in blood pressure control was seen between CLV and SNP, the safety profiles were similar between the 2 drugs. In addition, CLV remained less expensive than SNP for postoperative BP control. PMID- 27354746 TI - Enhancing the Budget Impact Model for Institutional Use: A Tool with Practical Applications for the Hospital Oncology Pharmacy. AB - BACKGROUND: The cost of cancer care is increasing, and tools are needed to understand the economic impact of new drugs on the hospital pharmacy budget. OBJECTIVE: To develop an interactive budget impact model (BIM) through a collaborative effort of industry, academia, and modeling experts to evaluate the use of a new agent in non-small cell lung cancer (NSCLC); this BIM included an institutional module specific to the needs of practices that purchase medications for use in institutional settings. METHODS: Treatment regimens, doses, duration of therapy, toxicity, and cost data are from published sources. All input data may be modified to match the local population. Outputs include cost of care, reimbursement, and margin overall and by treatment regimen. RESULTS: The base case assumes 20 NSCLC patients progressing after initial therapy (3 receiving ramucirumab+docetaxel, 2 bevacizumab+erlotinib, 3 docetaxel, 6 erlotinib, and 6 pemetrexed), wholesale acquisition cost (WAC) purchase price, and reimbursement at WAC+4.3%. The model estimated the total cost and reimbursement for the institutional oncology pharmacy to be $699,413 and $729,487, respectively, resulting in a margin of $30,075 (difference due to rounding) for the year for regimens utilized in the treatment of NSCLC in the post-progression setting. Results will vary depending on the input data. CONCLUSIONS: There is an increasing need for institutional pharmacies to plan ahead and anticipate the impact of new drugs on their oncology budgets. This interactive Excel-based institutional BIM may provide evidence-based support for pharmacy decision making. PMID- 27354748 TI - Reducing Readmission at an Academic Medical Center: Results of a Pharmacy Facilitated Discharge Counseling and Medication Reconciliation Program. AB - BACKGROUND: Hospital readmission has been identified as a key quality indicator and a target for reducing health care spending. OBJECTIVE: To evaluate the impact of a pharmacy-facilitated medication reconciliation and patient education model with post discharge follow-up on 30-day readmissions. METHODS: This prospective, historical control study included all patients admitted during a 6-month period to a general medicine unit with the highest 30-day readmission rate at Yale-New Haven Hospital. Patients were excluded if they expired prior to discharge, transferred, left against medical advice, were discharged to hospice, or were previously enrolled in the study. Upon admission, pharmacy technicians compiled the medication reconciliation information. Interventions were made by the pharmacist communicating with the patient's primary team. Medication and disease state counseling and final medication reconciliation were performed by the pharmacist before discharge. The primary outcome measure was 30-day readmission rates during the intervention period compared to the preceding 6 months and the same time period the previous year. Secondary outcomes included the total number of pharmacist-identified medication reconciliation interventions, total pharmacy resource utilization, and identification of patients at high risk for readmission. RESULTS: Study outcomes showed a 27% reduction in readmission during the intervention period. The pharmacist made a total of 546 medication interventions. The average pharmacist and pharmacy technician time per patient were 28.9 and 23.7 minutes, respectively. CONCLUSIONS: Pharmacy-facilitated medication reconciliation and patient education of medicine patients decreased 30 day readmission rates. PMID- 27354749 TI - Effect of the Implementation of Barcode Technology and an Electronic Medication Administration Record on Adverse Drug Events. AB - BACKGROUND: Hospitals have attempted to reduce adverse drug events (ADEs) by investing in new technologies, but data regarding their efficacy are lacking. OBJECTIVES: This study evaluates the effects of the implementation of barcode medication administration (BCMA) and electronic medication administration record (eMAR) technology on the profile of ADEs in a hospital setting. METHODS: We conducted a before-and-after study examining the effects of the implementation of BCMA and eMAR technology on the profile of ADEs at a 400-bed academic medical center by using incident reports. We compared reported ADEs in pre- and post implementation periods of 5 months to determine whether there was a reduction in the rate of ADEs within medication use phases. We further examined the severity of errors and described changes in the distribution of types of errors. RESULTS: A total of 775 electronic error-reporting system reports were included in this study: 397 (51%) in the pre-implementation period and 378 (49%) in the post implementation period. The rate of ADEs significantly decreased from 0.26% to 0.20% after implementation of the technology (relative risk [RR], 0.78; 95% CI, 0.67-0.89). The rate of transcription errors decreased from 0.089% to 0.036% (RR, 0.40; 95% CI, 0.30-0.54), which was largely attributed to reduction of "wrong time" errors. The rate of administration errors was identical in both groups at 0.017% (RR, 0.98; 95% CI 0.58-1.66). The mean severity level of administration errors significantly decreased from 4.44 to 3.23 (p = .005). CONCLUSION: The implementation of eMAR and BCMA technology improved patient safety by decreasing the overall rate of ADEs and the rate of transcription errors. These technologies also reduced the harmful impact to patients caused by administration errors. PMID- 27354750 TI - Uridine Triacetate. AB - Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433. The June 2016 monograph topics are elbasvir/grazoprevir, ixekizumab, brivaracetam, reslizumab, and sofosbuvir/velpatasvir. The Safety MUE is on reslizumab. PMID- 27354751 TI - Approvals, Submission, and Important Labeling Changes for US Marketed Pharmaceuticals. AB - This monthly feature will help readers keep current on new drug, new indications, dosage forms and safety-related changes in labeling or use. Efforts have been made to assure the accuracy of this information; however, if there are any questions, please let us know at jgeneral@ku.edu. PMID- 27354752 TI - Summaries of Safety Labeling Changes Approved by the FDA: Boxed Warnings Highlights. AB - As part of the US Food and Drug Administration's MedWatch program, safety labeling changes are reviewed and compiled monthly for drugs and therapeutic biologics where important changes have been made to the safety information. Boxed warnings (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guida ces/ucm075096.pdf) are ordinarily used to highlight either adverse reactions so serious in proportion to the potential benefit from the drug that it is essential that it be considered in assessing the risks and benefits of using the drugs or serious adverse reactions that can be prevented/reduced in frequency or severity by appropriate use of the drug; or FDA approved the drug with restrictions to ensure safe use because FDA concluded that the drug can be safely used only if distribution or use is restricted. There were 4 revised boxed warning from January through March 2016. PMID- 27354753 TI - Review of the 2015 Drug Supply Chain Security Act. AB - The integrity of the pharmaceutical supply chain is threatened by medication counterfeiting, importation of unapproved and substandard drugs, and grey markets - all of which have the potential to distribute drug products with the potential for serious harm. On November 27, 2013, President Obama signed into law Title II of the Drug Quality and Security Act, now known as the Drug Supply Chain Security Act (DSCSA). Over the next 10 years, the DSCSA will require the pharmaceutical supply chain to implement medication tracking and tracing; serialization, verification, and detection of suspicious products; and strict guidelines for wholesaler licensing and reporting. This article reviews the important aspects of the DSCSA and outlines the role of health-system pharmacy leaders in ensuring compliance to the DSCSA. By verifying that medication supplies are free from adulteration and tampering, the DSCSA serves as a foundational law to ensure quality in providing patient-centered pharmacy services. PMID- 27354754 TI - Digital Health Solutions: An Important Tool in Patient Engagement. AB - Hospitals and health systems are facing increased pressure to improve quality and outcomes while reducing expense. Quality-based reimbursement models are providing the necessary incentives for health care institutions to focus on issues such as avoidable hospital-acquired conditions and 30-day readmission rates. While our health care facilities certainly play a vital role in achieving optimal outcomes, patient engagement remains at the center of these efforts. PMID- 27354755 TI - Pneumatic Variable Series Elastic Actuator. AB - Inspired by human motor control theory, stiffness control is highly effective in manipulation and human-interactive tasks. The implementation of stiffness control in robotic systems, however, has largely been limited to closed-loop control, and suffers from multiple issues such as limited frequency range, potential instability, and lack of contribution to energy efficiency. Variable-stiffness actuator represents a better solution, but the current designs are complex, heavy, and bulky. The approach in this paper seeks to address these issues by using pneumatic actuator as a variable series elastic actuator (VSEA), leveraging the compressibility of the working fluid. In this work, a pneumatic actuator is modeled as an elastic element with controllable stiffness and equilibrium point, both of which are functions of air masses in the two chambers. As such, for the implementation of stiffness control in a robotic system, the desired stiffness/equilibrium point can be converted to the desired chamber air masses, and a predictive pressure control approach is developed to control the timing of valve switching to obtain the desired air mass while minimizing control action. Experimental results showed that the new approach in this paper requires less expensive hardware (on-off valve instead of proportional valve), causes less control action in implementation, and provides good control performance by leveraging the inherent dynamics of the actuator. PMID- 27354756 TI - Exposure of Secondary School Adolescents from Argentina and Mexico to Smoking Scenes in Movies: a Population-based Estimation. AB - BACKGROUND: Smoking scenes in movies promote adolescent smoking onset; thus, the analysis of the number of images of smoking in movies really reaching adolescents has become a subject of increasing interest. OBJECTIVE: The aim of this study was to estimate the level of exposure to images of smoking in movies watched by adolescents in Argentina and Mexico. METHODS: First-year secondary school students from Argentina and Mexico were surveyed. One hundred highest-grossing films from each year of the period 2009-2013 (Argentina) and 2010-2014 (Mexico) were analyzed. Each participant was assigned a random sample of 50 of these movies and was asked if he/she had watched them. The total number of adolescents who had watched each movie in each country was estimated and was multiplied by the number of smoking scenes (occurrences) in each movie to obtain the number of gross smoking impressions seen by secondary school adolescents from each country. RESULTS: Four-hundred and twenty-two movies were analyzed in Argentina and 433 in Mexico. Exposure to more than 500 million smoking impressions was estimated for adolescents in each country, averaging 128 and 121 minutes of smoking scenes seen by each Argentine and Mexican adolescent, respectively. Although 15, 16 and 18 rated movies had more smoking scenes in average, movies rated for younger teenagers were responsible for the highest number of smoking scenes watched by the students (67.3% in Argentina and 54.4% in Mexico) due to their larger audience. CONCLUSION: At the population level, movies aimed at children are responsible for the highest tobacco burden seen by adolescents. PMID- 27354757 TI - A stepwise approach for the management of capsular contraction syndrome in hinge based accommodative intraocular lenses. AB - PURPOSE: The aims of this study are to define the various stages of capsular contraction syndrome (CCS) and its effect on refractive error with hinge-based accommodating intraocular lenses (IOLs) and to describe a systematic approach for the management of the different stages of CCS. METHODS: Hinge-based accommodative IOLs function via flexible hinges that vault the optic forward during accommodation. However, it is the flexibility of the IOL that makes it prone to deformation in the event of CCS. The signs of CCS are identified and described as posterior capsular striae, fibrotic bands across the anterior or posterior capsule, and capsule opacification. Various degrees of CCS may affect hinge-based accommodating IOLs in a spectrum from subtle changes in IOL appearance to significant increases in refractive error and loss of uncorrected visual acuity. The signs of CCS and its effect on IOL position and the resulting changes in refractive error are matched to appropriate treatment plans. RESULTS: A surgeon can avoid CCS and manage the condition if familiar with the early signs of CCS. If CCS is identified, yttrium-aluminum-garnet laser capsulotomy should be considered. If moderate CCS occurs, it may be effectively treated with insertion of a capsular tension ring. If CCS is allowed to progress to advanced stages, an IOL exchange may be necessary. CONCLUSION: Surgeons should be familiar with the stages of CCS and subsequent interventions. The steps outlined in this article help to guide surgeons in the prevention and management of CCS with hinge-based accommodative IOLs in order to provide improved refractive outcomes for patients. PMID- 27354758 TI - Ranibizumab in neovascular age-related macular degeneration: a 5-year follow-up. AB - PURPOSE: Our aim was to evaluate an optical coherence tomography (OCT) and visual acuity (VA)-guided, variable-dosing regimen with intravitreal ranibizumab injection for treating patients with neovascular age-related macular degeneration (AMD) from 2007 to 2012. DESIGN: This was a retrospective clinical study of 5 years follow-up in a tertiary eye center. PATIENTS AND METHODS: In this study, 66 patients with neovascular AMD (mean age of 74 years, SD 8.7 years) were included. We investigated the development of best-corrected visual acuity (BCVA), the number of intravitreal injections, and the central retinal thickness measured with OCT (OCT Spectralis) over 5 years of intravitreal treatment. RESULTS: The mean number of intravitreal ranibizumab injections over 5 years was 8.8. The mean BCVA before therapy was 0.4 logarithm of the minimum angle of resolution (logMAR). After 5 years of therapy, the mean BCVA was 0.6 logMAR. In all, 16% of treated patients had stable VA over 5 years and 10% of study eyes approved their VA. The mean OCT-measured central retinal thickness at the beginning of this study was 295 um; after 5 years of treatment, the mean central retinal thickness was 315 um. There was an increase in central retinal thickness in 47.5% of examined eyes. CONCLUSION: Other studies showed VA improvement in OCT-guided variable-dosing regimens. Our study revealed a moderate decrease in VA after a total mean injection number as low as 8.8 injections over 5 years. In OCT, an increase in central retinal thickness over 5 years could be observed. Probably, this is due to deficient treatment when comparing the total injection number to other treatment regimens. Anti-VEGF therapy helps to keep the VA stable for a period of time, but cannot totally stop the progression of the disease completely. Patients with late stages of neovascular AMD can maintain VA even if they are relatively undertreated. PMID- 27354759 TI - Worsening anatomic outcomes following aflibercept for neovascular age-related macular degeneration in eyes previously well controlled with ranibizumab. AB - PURPOSE: Antivascular endothelial growth factor injection is the mainstay of treating neovascular age-related macular degeneration (AMD). Previous studies have shown that switching treatment from ranibizumab to aflibercept led to an improvement in eyes with recalcitrant activity. Herein, we identify a unique subset of patients whose eyes with neovascular AMD were previously well controlled with ranibizumab injections were then worsened after being switched to aflibercept. METHODS: This is a retrospective interventional case series. Eyes with neovascular AMD, previously well controlled with monthly injections of ranibizumab, which then developed worsening of subretinal fluid after being switched to aflibercept were included. RESULTS: A total of 17 eyes were included. All eyes developed increased subretinal fluid when switched from ranibizumab to aflibercept. Fourteen patients were switched back to ranibizumab after a single injection of aflibercept and had subsequent rapid resolution of subretinal fluid. Three patients continued with monthly aflibercept injections for two subsequent months and demonstrated the persistence of the increased subretinal fluid until they were switched back to treatment with ranibizumab at which time the fluid resolved. No eye had persistent decline in visual acuity. CONCLUSION: Switching from intravitreal ranibizumab to aflibercept in eyes with well-controlled neovascular AMD may result in worsening in a subset of patients and resolves when therapy is switched back to ranibizumab. PMID- 27354760 TI - Meta-analysis and review: effectiveness, safety, and central port design of the intraocular collamer lens. AB - The purpose of this review is to summarize relevant data from publications appearing in the peer-reviewed scientific literature over the past decade since US Food and Drug Administration approval of the implantable collamer lens (ICL), and, in particular, to review studies relating to sizing methodology, safety, and effectiveness, as well as more recent studies reporting clinical outcomes of the V4c Visian ICL with KS Aquaport, VICMO. A literature search was conducted using two databases, PubMed.gov and Science.gov, to identify all articles published after 2005 related to the Visian ICL (STAAR Surgical, Inc.). Articles were examined for their relevance to sizing methodology, clinical safety, and effectiveness, and the references cited in each article were also searched for additional relevant publications. The literature review revealed that all currently reported methods of determining the best-fit size of the ICL achieve similarly satisfactory results in terms of vault, the safe distance between the crystalline lens and the ICL. Specifically, meta-analysis demonstrated that sulcus-to-sulcus and white-to-white measurement-based sizing methods do not result in clinically meaningful nor statistically significant differences in vault (two-sample two-sided t-test using pooled mean and standard deviations; t (2,594)=1.33; P=0.18). The reported rates of complications related to vault are very low, except in two case series where additional risk factors such as higher levels of myopia and older age impacted the incidence of cataract. On the basis of preclinical studies and initial clinical reports, with up to 5 years of follow up, the new VICMO central port design holds promise for further reduction of complications. Given its safety record and the significant improvement in vision and quality of life that the ICL makes possible, the benefits of ICL implantation outweigh the risks. PMID- 27354761 TI - The effect of long-term use of intranasal steroids on intraocular pressure. AB - Long-term use of topical nasal steroids (especially older generation steroids) has been shown to elevate intraocular pressure (IOP), but newer intranasal steroids are thought to have a minimal effect on IOP because of their low bioavailability. This study aimed to investigate alterations in IOP with two commonly used intranasal steroids for a 6-month period of time. One-hundred allergic rhinitis patients, divided equally into two groups, used mometasone furoate and fluticasone furoate intranasal steroids for 6 months. IOPs were measured before treatment and repeated at the 3rd, 6th, 12th, and 24th weeks of treatment. The IOPs of the groups were then compared. No statistically significant alteration was observed between the groups during the treatment time period. It was found that new generation intranasal steroids can be used safely, and there may not be an increased risk of IOP elevation in prolonged use in normal healthy people. PMID- 27354762 TI - Development of lifitegrast: a novel T-cell inhibitor for the treatment of dry eye disease. AB - Dry eye disease (DED) is a multifactorial disorder of the ocular surface characterized by symptoms of discomfort, decreased tear quality, and chronic inflammation that affects an estimated 20 million patients in the US alone. DED is associated with localized inflammation of the ocular surface and periocular tissues leading to homing and activation of T cells, cytokine release, and development of hyperosmolar tears. This inflammatory milieu results in symptoms of eye dryness and discomfort. Homing of T cells to the ocular surface is influenced by the binding of lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18; alphaLbeta2), a cell surface adhesion protein, to its cognate ligand, intercellular adhesion molecule-1 (ICAM-1; CD54), which is expressed on inflamed ocular/periocular epithelium and vascular endothelium. LFA-1/ICAM-1 binding within the immunologic synapse enables both T-cell activation and cytokine release. Lifitegrast is a novel T-cell integrin antagonist that is designed to mimic the binding epitope of ICAM-1. It serves as a molecular decoy to block the binding of LFA-1/ICAM-1 and inhibits the downstream inflammatory process. In vitro studies have demonstrated that lifitegrast inhibits T-cell adhesion to ICAM 1-expressing cells and inhibits secretion of pro-inflammatory cytokines including interferon gamma, tumor necrosis factor alpha, macrophage inflammatory protein 1 alpha, interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, and IL-6, all of which are known to be associated with DED. Lifitegrast has the potential to be the first pharmaceutical product approved in the US indicated for the treatment of both symptoms and signs of DED. Clinical trials involving over 2,500 adult DED patients have demonstrated that topically administered lifitegrast 5.0% ophthalmic solution can rapidly reduce the symptoms of eye dryness and decrease ocular surface staining with an acceptable long-term safety profile. The purpose of this review is to highlight the developmental story - from bench top to bedside - behind the scientific rationale, engineering, and clinical experience of lifitegrast for the treatment of DED. PMID- 27354764 TI - Role of cytochrome P450 2D6 genetic polymorphism in carvedilol hydroxylation in vitro. AB - Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic enzyme that catalyzes the metabolism of a great number of therapeutic drugs. Up to now, >100 allelic variants of CYP2D6 have been reported. Recently, we identified 22 novel variants in the Chinese population in these variants. The purpose of this study was to examine the enzymatic activity of the variants toward the CYP2D6 substrate carvedilol in vitro. The CYP2D6 proteins, including CYP2D6.1 (wild type), CYP2D6.2, CYP2D6.10, and 22 other novel CYP2D6 variants, were expressed from insect microsomes and incubated with carvedilol ranging from 1.0 MUM to 50 MUM at 37 degrees C for 30 minutes. After termination, the carvedilol metabolites were extracted and detected using ultra-performance liquid chromatography tandem mass spectrometry. Among the 24 CYP2D6 variants, CYP2D6.92 and CYP2D6.96 were catalytically inactive and the remaining 22 variants exhibited significantly decreased intrinsic clearance values (ranging from ~25% to 95%) compared with CYP2D6.1. The present data in vitro suggest that the newly found variants significantly reduced catalytic activities compared with CYP2D6.1. Given that CYP2D6 protein activities could affect carvedilol plasma levels, these findings are greatly relevant to personalized medicine. PMID- 27354763 TI - Molecular mechanisms of cisplatin resistance in cervical cancer. AB - Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%-20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer. PMID- 27354766 TI - The efficacy of nebulized magnesium sulfate alone and in combination with salbutamol in acute asthma. AB - OBJECTIVE: Evaluation of the efficacy of nebulized magnesium sulfate (MgSO4) alone and in combination with salbutamol in acute asthma. METHODS: A double-blind randomized controlled study was conducted in Chest and Emergency Departments. Thirty patients of acute attack of bronchial asthma were randomized into three groups: MgSO4 nebulization (group A), salbutamol nebulization (group B), and their combination (group C). All patients were monitored before and after nebulization (each 20 minutes) for peak expiratory flow rate (PEFR), respiratory rate (RR), heart rate (HR), blood pressure, pulsus paradoxus, oxygen saturation, clinical examination, and Fischl index. RESULTS: A highly significant improvement in PEFR, PEFR percentage, and Fischl index and significant decrease in RR and HR was observed in all groups. A similar improvement in PEFR was observed in group A and group B (P=0.389). The difference in peak expiratory flow (PEF) improvement was insignificant between group B and group C (P=0.101), while there was a significant difference between group A and group C (P=0.014) in favor of group C. CONCLUSION: Nebulized MgSO4 alone or combined with salbutamol has a clinically significant bronchodilator effect in acute asthma and leads to clinical improvement, increase in PEFR, reduction in HR, and reduction in RR. The response to nebulized MgSO4 alone (PEFR improvement 54+/-35.6 L/min, P=0.001) is comparable (P=0.389) to that of nebulized salbutamol (PEFR improvement 67.0+/ 41.9 L/min, P=0.001) and is significantly less than (P=0.014) that of nebulized combination (PEFR improvement 92.0+/-26.9 L/min, P=0.000). PMID- 27354765 TI - In vivo gastric residence and gastroprotective effect of floating gastroretentive tablet of DA-9601, an extract of Artemisia asiatica, in beagle dogs. AB - OBJECTIVE: DA-9601, an extract of Artemisia asiatica containing eupatilin and jaceosidin as active compounds, has been prescribed to treat gastritis in Asia. In recent times, sustained-release, floating gastroretentive (GR) tablets of DA 9601 are available on the market. In the present study, the physical properties and in vitro drug release profile, in vivo gastric residence time, and gastroprotective effect of GR tablet were compared to those of immediate release (IR) tablets of DA-9601. METHOD: In vitro buoyancy behavior (floating lag time and duration) and release profile of eupatilin were assessed in acidic medium. The in vivo intragastric behaviors of the barium sulfate-loaded IR and GR tablets were evaluated in beagle dogs by radiographic studies. Local gastroprotective effect was compared in an experimentally induced gastric lesion in beagle dogs after oral administration of IR (three times per day) or GR (twice daily) tablets for 15 days. RESULTS: Upon contact with gastric juice, a low-density floating tablet (apparent density of 0.93 g/cm(3)) was buoyant on the medium and was upheld for 14 hours, providing sustained drug release profile, whereas the IR tablet disintegrated within 10 minutes, showing complete drug release within 2 hours. In vivo radiographic studies showed that the GR tablet was retained for >4 hours in the stomach. Both DA-9601 formulations remarkably alleviated gastric mucosal injury compared to placebo group, when observed by gastric endoscopy. CONCLUSION: Twice-daily GR tablets exhibited a prolonged gastric residence time and a remarkable mucosal restoration effect in animal models. Therefore, the GR system of DA-9601 could be a substitute dosage form for the treatment of gastritis, while reducing the dosing frequency and thus improving patient compliance. PMID- 27354767 TI - Inhibitory effects of compounds from Phyllanthus amarus on nitric oxide production, lymphocyte proliferation, and cytokine release from phagocytes. AB - Standardized extract of Phyllanthus amarus has previously been shown to have a strong inhibitory effect on phagocytic activity of human neutrophils. The current study was carried out to evaluate the effects of constituents of the extract of P. amarus on nitric oxide (NO) production as well as lymphocyte proliferation and cytokine release from phagocytes. Three compounds, ethyl 8-hydroxy-8-methyl tridecanoate, 7beta,19alpha dihydroxy-urs-12-ene, and 1,7,8-trihydroxy-2 naphtaldehyde, together with seven known compounds were isolated from the whole plant of P. amarus. The isolated compounds and reference standards, ie, gallic acid, ellagic acid, corilagin, and geraniin, which were quantitatively analyzed in the extracts, were evaluated for their effects on immune cells. Among the compounds tested, the lignans, especially phyltetralin and phyllanthin, showed strong inhibition on lymphocyte proliferation with half maximal inhibitory concentration (IC50) values of 1.07 MUM and 1.82 MUM, respectively. Ethyl 8 hydroxy-8-methyl-tridecanoate and 1,7,8-trihydroxy-2-naphtaldehyde exhibited strong inhibition on nitric oxide production with IC50 values of 0.91 MUM and 1.07 MUM, respectively. Of all the compounds, corilagin was the strongest inhibitor of tumor necrosis factor-alpha release with an IC50 value of 7.39 MUM, whereas geraniin depicted the strongest inhibitory activity on interleukin-1beta release with an IC50 value of 16.41 MUM. The compounds constituting the extract of P. amarus were able to inhibit the innate immune response of phagocytes at different steps. PMID- 27354768 TI - A validated measure of adherence to antibiotic prophylaxis in children with sickle cell disease. AB - BACKGROUND: Antibiotic prophylaxis is a mainstay in sickle cell disease management. However, adherence is estimated at only 66%. This study aimed to develop and validate a Sickle Cell Antibiotic Adherence Level Evaluation (SCAALE) to promote systematic and detailed adherence evaluation. METHODS: A 28-item questionnaire was created, covering seven adherence areas. General Adherence Ratings from the parent and one health care provider and medication possession ratios were obtained as validation measures. RESULTS: Internal consistency was very good to excellent for the total SCAALE (alpha=0.89) and four of the seven subscales. Correlations between SCAALE scores and validation measures were strong for the total SCAALE and five of the seven subscales. CONCLUSION: The SCAALE provides a detailed, quantitative, multidimensional, and global measurement of adherence and can promote clinical care and research. PMID- 27354769 TI - Development of a new diabetes medication self-efficacy scale and its association with both reported problems in using diabetes medications and self-reported adherence. AB - BACKGROUND: Although there are several different general diabetes self-efficacy scales, there is a need to develop a self-efficacy scale that providers can use to assess patient's self-efficacy regarding medication use. The purpose of this study was to: 1) develop a new diabetes medication self-efficacy scale and 2) examine how diabetes medication self-efficacy is associated with patient-reported problems in using diabetes medications and self-reported adherence. PATIENTS AND METHODS: Adult English-speaking patients with type 2 diabetes were recruited from a family medicine clinic and a pharmacy in Eastern North Carolina, USA. The patients were eligible if they reported being nonadherent to their diabetes medicines on a visual analog scale. Multivariable regression was used to examine the relationship between self-efficacy and the number of reported diabetes medication problems and adherence. RESULTS: The diabetes medication self-efficacy scale had strong reliability (Cronbach's alpha =0.86). Among a sample (N=51) of mostly African-American female patients, diabetes medication problems were common (6.1+/-3.1) and a greater number of diabetes medications were associated with lower medication adherence (odds ratio: 0.35; 95% confidence interval: 0.13, 0.89). Higher medication self-efficacy was significantly related to medication adherence (odds ratio: 1.17; 95% confidence interval: 1.05, 1.30) and inversely related to the number of self-reported medication problems (beta=-0.13; P=0.006). CONCLUSION: Higher diabetes medication self-efficacy was associated with fewer patient-reported medication problems and better medication adherence. Assessing medication-specific self-efficacy may help to identify medication-related problems that providers can help the patients address, potentially improving adherence and patient outcomes. PMID- 27354770 TI - Treatment-related decisional conflict in patients with depressive and anxious disorders. AB - PURPOSE: To determine the level of treatment-related decisional conflict in patients with emotional disorders and to establish its relationship with sociodemographic and clinical variables. METHODS: We conducted a cross-sectional survey on a convenience sample of 321 consecutive psychiatric outpatients with emotional disorders. All patients completed self-report questionnaires assessing sociodemographic and clinical variables, patients' preference of participation in decision making, perceived decisional conflict about treatment, adherence to prescribed treatment, and satisfaction with the psychiatric care provided. Multiple correspondences analysis was used to investigate relationships of decisional conflict with the variables of interest. RESULTS: Approximately, two thirds of psychiatric outpatients self-reported decisional conflict regarding their treatment. Interestingly, the presence of decisional conflict did not influence significantly patients' preferences of participation or their adherence to prescribed treatment. Patients without decisional conflict registered significantly higher satisfaction. Multiple correspondences analysis evidenced two clear profiles: patients without decisional conflict received the treatment they preferred, mainly psychotherapy or combined treatment, had been under psychiatric treatment for longer than 5 years, and self-reported high satisfaction with health care received; on the other hand, patients with decisional conflict did not receive the treatment they preferred, were treated with pharmacotherapy alone for a period of time between 1 and 5 years, and self reported medium satisfaction with received health care. CONCLUSION: The high level of decisional conflict found in patients with depression and anxiety attending a secondary care service could be an important driving force when personalizing and tailoring information and teaching skills to patients about their illnesses and their treatments. PMID- 27354771 TI - Impact of strabismus on the quality of life of Chinese Han teenagers. AB - BACKGROUND: Although much research has been conducted on the impact of strabismus on the quality of life (QoL) of adults, the effect of this condition on teenagers has not been extensively studied. This study therefore aimed to assess the effect of strabismus on the vision-related QoL of Chinese teenagers. METHODS: The Chinese version of the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) was self-administered by 1,040 teenagers with strabismus and 1,002 individuals with normal vision. All the participants were from the Chinese Han population. The independent samples t-test was used to compare QoL between teenagers with and without strabismus. RESULTS: The majority of scores on the NEI-VFQ-25 domains were significantly different between the two groups. QoL was significantly lower in individuals with strabismus compared with teenagers with normal vision on all domains, with the exception of social functioning. CONCLUSION: Statistically significantly lower vision-related QoL scores were found in Chinese Han teenagers with strabismus compared with those without strabismus. PMID- 27354772 TI - Cost-effectiveness analysis of universal noninvasive testing for post-treatment confirmation of Helicobacter pylori eradication and the impact of patient adherence. AB - BACKGROUND: The treatment failure rate for Helicobacter pylori eradication therapy is ~20% due to poor patient compliance and increased antibiotic resistance. This analysis assessed the cost-effectiveness of universal post treatment testing to confirm eradication of H. pylori infection in adults. METHODS: Decision-analytic models evaluated the cost-effectiveness of universal post-treatment testing (urea breath test [UBT] or monoclonal fecal antigen test [mFAT]) vs no testing (Model 1), and UBT vs mFAT after adjusting for patient adherence to testing (Model 2) in adults who previously received first-line antimicrobial therapy. Patients testing positive received second-line quadruple therapy; no further action was taken for those testing negative or with no testing (Model 1) or for those nonadherent to testing (Model 2). In addition to testing costs, excess lifetime costs and reduced quality-adjusted life-years (QALYs) due to continuing H. pylori infection were considered in the model. RESULTS: Expected total costs per patient were higher for post-treatment testing (UBT: US$325.76; mFAT: US$242.12) vs no testing (US$182.41) in Model 1 and for UBT (US$336.75) vs mFAT (US$326.24) in Model 2. Expected QALYs gained per patient were 0.71 and 0.72 for UBT and mFAT, respectively, vs no testing (Model 1), and the same was 0.37 for UBT vs mFAT (Model 2). The estimated incremental costs per QALY gained for post-treatment testing vs no testing were US$82.90-US$202.45 and, after adjusting for adherence, US$28.13 for UBT vs mFAT. CONCLUSION: Universal post-treatment testing was found to be cost-effective for confirming eradication of H. pylori infection following first-line therapy. Better adherence to UBT relative to mFAT was the key to its cost-effectiveness. PMID- 27354773 TI - Psychosocial impact of dental aesthetics and desire for orthodontic treatment among Chinese undergraduate students. AB - OBJECTIVE: The objective of this study is to evaluate the psychosocial impact of dental aesthetics in undergraduate students in the People's Republic of China and to investigate the association between normal orthodontic treatment needs, psychosocial impact of dental aesthetics, and desire for orthodontic treatment. MATERIALS AND METHODS: A cross-sectional study was carried out in two universities in a city of the People's Republic of China with 374 young adults aged between 19 years and 24 years. The students answered a Chinese version of the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) and addressed their desire for orthodontic treatment. Objective malocclusion severity was assessed with the Index of Orthodontic Treatment Need (IOTN). Statistical analysis was performed by the SPSS software (Version 15.0). RESULTS: There was no statistical sex difference in relation to the dental health component of IOTN (P=0.893) and PIDAQ scores (P=0.06), but it was found that the desire for orthodontic treatment was significantly stronger among females. The total and subscale PIDAQ scores and malocclusion severity differed significantly among the five grades of desire (P<0.01). Significant positive correlation was found among desire for orthodontic treatment, IOTN-dental health component grades, and total or subscale PIDAQ scores (P<0.01). High correlation was found between desire and PIDAQ score (r=0.93). CONCLUSION: The desire for orthodontic treatment is higher among female young adults who have the same orthodontic treatment needs compared to males. The desire for orthodontic treatment has high positive correlation with PIDAQ scores and increases with the increase in self-perceived psychosocial impacts of malocclusion and the needs for orthodontic treatment. PMID- 27354774 TI - Magnetic resonance enterography or video capsule endoscopy - what do Crohn's disease patients prefer? AB - BACKGROUND: Despite differences in the information obtained by capsule endoscopy (CE) and magnetic resonance enterography (MRE), one of these modalities is usually needed when evaluating disease activity. There are no data on patients' preference that would help guide the choice between these two modalities in these instances. AIM: To compare patients' tolerance and preference to MRE versus CE. PATIENTS AND METHODS: Patients with known small bowel Crohn's disease (CD) in clinical remission (Crohn's disease activity index [CDAI] <150) or with mild symptoms (CDAI <220) were prospectively recruited. All patients underwent MRE followed by CE. Patients were asked to fill out a questionnaire addressing specific points regarding inconvenience during the preparation for the procedures, the procedures, and postprocedures. Side effects and procedure preference were addressed. Questionnaires were included for analysis only when more than 95% of the items were addressed. RESULTS: Fifty-six patients fulfilled inclusion criteria. Pre-exam discomfort, during-exam discomfort, nausea, vomiting, bloating, and abdominal pain were all significantly more prominent in MRE as compared to CE (P<0.0001, P<0.0001, P<0.0001, P=0.009, P=0.0002, P<0.0001, respectively). MRE was perceived as a more difficult procedure (P<0.0001). Furthermore, MRE was associated with a specific adverse event - claustrophobia. Seventy-eight percent of patients (44 patients) preferred to repeat CE as compared to 22% (P<0.0001) who preferred MRE. CONCLUSION: CE was better tolerated by CD patients compared to MRE and was preferred by 78% of patients. The superior tolerability of CE should be considered along with the diagnostic features, and more data sought when choosing between these two modalities for CD patients for long-term follow-up. PMID- 27354775 TI - Patients' management of type 2 diabetes in Middle Eastern countries: review of studies. AB - The increased prevalence of diabetes in Middle Eastern countries is a health policy priority. Important risk factors for diabetes have been identified. Lifestyle interventions and adherence to medications are central to disease prevention and management. This review focuses on the management of type 2 diabetes mellitus in Middle Eastern countries. The aim is to identify the ways in which knowledge, health beliefs, and social and cultural factors influence adherence to medication and lifestyle measures. Thirty-four studies were identified following a systematic search of the literature. The studies describe the influence of knowledge, health beliefs, culture, and lifestyle on the management of type 2 diabetes mellitus in the Middle East. Findings indicate a lack of health knowledge about diabetes among populations, which has implications for health behaviors, medication adherence, and treatment outcomes. Many identified health beliefs and cultural lifestyle factors, such as religious beliefs, beliefs about fasting during Ramadan, and sedentary lifestyles played a role in patients' decisions. For better management of this disease, a collaborative approach between patients, their families, health care professionals, and governments should be adopted. Implementing behavioral strategies and psychological interventions that incorporate all health care professionals in the management process have been shown to be effective methods. Such services help patients change their behavior. However, the utilization of such services and interventions is still limited in Arabian countries. Physicians in the Middle East are the health care professionals most involved in the care process. PMID- 27354776 TI - Underestimated factors may also precipitate delirium and can lead to the misinterpretation of frailty in these patients. PMID- 27354777 TI - Asthma-chronic obstructive pulmonary disease overlap syndrome in the urban Chinese population: prevalence and disease burden using the 2010, 2012, and 2013 China National Health and Wellness Surveys. AB - BACKGROUND: Research has suggested a significant burden for patients with asthma chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS). However, few studies have studied this population in the People's Republic of China, a region in the midst of rapid epidemiological change with respect to respiratory disease. The aim of this study was to assess the prevalence of ACOS and its association with patient outcomes in urban China. METHODS: Data from the 2010, 2012, and 2013 China National Health and Wellness Survey, an Internet-based survey of adults in urban China, were used (N=59,935). Respondents were categorized into one of four groups based on self-reported physician diagnoses: ACOS, asthma only, COPD only, or control (ie, no asthma or COPD). A propensity score matching procedure was conducted to cull the control group into a subgroup (ie, matched controls) who resembled patients with ACOS, asthma only, and COPD only. These four groups (ACOS, asthma only, COPD only, matched controls) were then compared with respect to health status (Short Form-12 version 2/Short Form 36 version 2), work productivity, and health care resource use using generalized linear models. RESULTS: Patients with ACOS (N=366) comprised 0.61% of the adult population, 30.73% of the asthma population, and 18.60% of the COPD population in the People's Republic of China. Patients with ACOS reported significantly worse health status (eg, health utilities =0.63, 0.66, 0.63, and 0.69 for ACOS, COPD only, asthma only, and matched controls, respectively) and significantly greater work impairment (eg, overall work impairment =43.65%, 35.19%, 48.55%, and 29.80%, respectively) and health care resource use (eg, physician visits in the past 6 months =5.13, 3.84, 4.65, and 2.39, respectively) compared with matched controls and patients with COPD only. Few significant differences were observed between patients with ACOS and asthma only. CONCLUSION: Patients with ACOS have a greater comorbidity burden and significantly worse health outcomes compared with COPD only patients and matched controls. Better management of these patients may help to improve their outcomes. PMID- 27354778 TI - Development of a Barthel Index based on dyspnea for patients with respiratory diseases. AB - BACKGROUND: As Barthel Index (BI) quantifies motor impairment but not breathlessness, the use of only this index could underestimate disability in chronic respiratory disease (CRD). To our knowledge, no study evaluates both motor and respiratory disability in CRD during activities of daily living (ADLs) simultaneously and with a unique tool. The objective of this study was to propose for patients with CRD an additional tool for dyspnea assessment during ADLs based on BI items named Barthel Index dyspnea. METHODS: Comprehensibility, reliability, internal consistency, validity, responsiveness, and ability to differentiate between disease groups were assessed on 219 subjects through an observational study performed in an in-hospital rehabilitation setting. RESULTS: Good comprehensibility, high reliability (interrater intraclass correlation coefficient was 0.93 [95% confidence interval 0.892-0.964] and test-retest intraclass correlation coefficient was 0.99 [95% confidence interval 0.983 0.994]), good internal consistency (Cronbach's alpha 0.89), strong concurrent validity with 6 minute walking distance (Pearson r=-0.538, P<0.001) and Medical Research Council (Spearman r S=0.70, P<0.001), good responsiveness after rehabilitation (P<0.001), and good appropriateness of the index were found evidencing patients with different dyspnea severity. Divergent validity showed weak correlation (Pearson r=-0.38) comparing Barthel Index dyspnea and BI. CONCLUSION: The BI based on dyspnea perception proved to be reliable, sensitive, and adequate as a tool for measuring the level of dyspnea perceived in performing basic daily living activities. A unique instrument simultaneously administered may provide a global assessment of disability during ADLs incorporating both motor and respiratory aspects. PMID- 27354779 TI - Smokers with emphysema and small airway disease on computed tomography have lower bone density. AB - Osteoporosis is more common in patients with COPD and in smokers. The aim of this study was to assess whether measures of emphysema and airway disease on computed tomography (CT) were associated with lower bone density or vertebral fractures in smokers with and without COPD. For this purpose, we included participants from the NELSON lung cancer screening trial. Bone density was measured as Hounsfield Units in the first lumbar vertebra, and vertebral fractures were assessed semiquantitatively. The 15th percentile method (Perc15) was used to assess emphysema, and the airway lumen perimeter (Pi10) was used for airway wall thickness. Expiratory/inspiratory-ratiomean lung density (E/I-ratioMLD) was used as a measure for air trapping and tracheal index to assess tracheal deformity. Linear regression models and logistic regression models were used to assess associations between CT biomarkers, bone density, and presence of fractures. Exactly 1,093 male participants were eligible for analysis. Lower Perc15 and higher E/I-ratioMLD were significantly associated with lower bone density (b= 1.27, P=0.02 and b=-0.37, P=0.02, respectively). Pi10 and tracheal index were not associated with bone density changes. CT-derived biomarkers were not associated with fracture prevalence. Bone density is lower with increasing extent of emphysema and small airway disease but is not associated with large airway disease and tracheal deformity. This may indicate the necessity to measure bone density early in smokers with emphysema and air trapping to prevent vertebral fractures. PMID- 27354780 TI - Agreement between a simple dyspnea-guided treatment algorithm for stable COPD and the GOLD guidelines: a pilot study. AB - INTRODUCTION: Guidelines recommendations for the treatment of COPD are poorly followed. This could be related to the complexity of classification and treatment algorithms. The purpose of this study was to validate a simpler dyspnea-based treatment algorithm for inhaled pharmacotherapy in stable COPD, comparing its concordance with the current Global Initiative for Obstructive Lung Disease (GOLD) guideline. METHODS: We enrolled patients who had been diagnosed with COPD in three primary care facilities and two tertiary hospitals in Spain. We determined anthropometric data, forced expiratory volume in the 1st second (percent), exacerbations, and dyspnea based on the modified Medical Research Council scale. We evaluated the new algorithm based on dyspnea and exacerbations and calculated the concordance with the current GOLD recommendations. RESULTS: We enrolled 100 patients in primary care and 150 attending specialized care in a respiratory clinic. There were differences in the sample distribution between cohorts with 41% vs 26% in grade A, 16% vs 12% in grade B, 16% vs 22% in grade C, and 27% vs 40% in grade D for primary and respiratory care, respectively (P=0.005). The coincidence of the algorithm with the GOLD recommendations in primary care was 93% and 91.8% in the respiratory care cohort. CONCLUSION: A simple dyspnea-based treatment algorithm for inhaled pharmacotherapy of COPD could be useful in the management of COPD patients and concurs very well with the recommended schema suggested by the GOLD initiative. PMID- 27354781 TI - Prompt initiation of maintenance treatment following a COPD exacerbation: outcomes in a large insured population. AB - BACKGROUND: The aim of this study was to extend previous findings and determine the value of prompt initiation of maintenance treatment (MT) following COPD exacerbations requiring hospitalization or an emergency department (ED) visit. PATIENTS AND METHODS: Administrative claims data (collected between January 1, 2009 and June 30, 2012) from an employer-sponsored commercially insured population were retrospectively used to identify patients with a COPD exacerbation resulting in hospitalization or an ED visit. Patients initiating approved MT for COPD within 30 days of discharge/diagnosis (prompt) were compared with those initiating MT within 31-180 days (delayed). COPD-related total, medical, and prescription drug costs during a 1-year follow-up period were evaluated using semilog ordinary least square regressions, controlling for baseline characteristics plus COPD-related costs from the previous year. The odds and number of subsequent COPD-related exacerbations during the follow-up were compared between the prompt and delayed cohorts using logistic regression and zero-inflated negative binomial models, respectively. RESULTS: A total of 6,521 patients with a COPD-related hospitalization or an ED visit were included, of whom 4,555 received prompt MT and 1,966 received delayed MT. Adjusted COPD related total and medical costs were significantly lower for the prompt MT than the delayed MT cohorts (US$3,931 vs US$4,857 and US$2,327 vs US$3,087, respectively; both P<0.010), as were COPD-related prescription costs (US$1,526 vs US$1,683, P<0.010) during the 1-year follow-up period. Patients receiving delayed MT were 68% more likely to have a subsequent exacerbation requiring hospitalization and 80% more likely to have an exacerbation requiring an ED visit. CONCLUSION: Prompt initiation of MT following a COPD-related hospitalization or an ED visit was associated with a significant reduction in COPD-related costs and odds of exacerbation in the following year compared with delayed initiation. PMID- 27354782 TI - Efficacy and safety of twice-daily glycopyrrolate in patients with stable, symptomatic COPD with moderate-to-severe airflow limitation: the GEM1 study. AB - BACKGROUND: The purpose of this study was to confirm the efficacy and safety of twice-daily glycopyrrolate 15.6 ug, a long-acting muscarinic antagonist, in patients with stable, symptomatic, chronic obstructive pulmonary disease (COPD) with moderate-to-severe airflow limitation. METHODS: The GEM1 study was a 12 week, multicenter, double-blind, parallel-group, placebo-controlled study that randomized patients with stable, symptomatic COPD with moderate-to-severe airflow limitation to twice-daily glycopyrrolate 15.6 ug or placebo (1:1) via the Neohaler((r)) device. The primary objective was to demonstrate superiority of glycopyrrolate versus placebo in terms of forced expiratory volume in 1 second area under the curve between 0 and 12 hours post morning dose at week 12. Other outcomes included additional spirometric end points, transition dyspnea index, St George's Respiratory Questionnaire, COPD Assessment Test, rescue medication use, and symptoms reported by patients via electronic diary. Safety was also assessed during the study. RESULTS: Of the 441 patients randomized (glycopyrrolate, n=222; placebo, n=219), 96% of patients completed the planned treatment phase. Glycopyrrolate demonstrated statistically significant (P<0.001) improvements in lung function versus placebo. Glycopyrrolate showed statistically significant improvement in the transition dyspnea index focal score, St George's Respiratory Questionnaire total score, COPD Assessment Test score, rescue medication use, and daily total symptom score versus placebo at week 12. Safety was comparable between the treatment groups. CONCLUSION: Significant improvement in lung function, dyspnea, COPD symptoms, health status, and rescue medication use suggests that glycopyrrolate is a safe and effective treatment option as maintenance bronchodilator in patients with stable, symptomatic COPD with moderate-to-severe airflow limitation. PMID- 27354783 TI - Lung perfusion and emphysema distribution affect the outcome of endobronchial valve therapy. AB - The exclusion of collateral ventilation (CV) and other factors affect the clinical success of endoscopic lung volume reduction (ELVR). However, despite its benefits, the outcome of ELVR remains difficult to predict. We investigated whether clinical success could be predicted by emphysema distribution assessed by computed tomography scan and baseline perfusion assessed by perfusion scintigraphy. Data from 57 patients with no CV in the target lobe (TL) were retrospectively analyzed after ELVR with valves. Pulmonary function tests (PFT), St George's Respiratory Questionnaire (SGRQ), and 6-minute walk tests (6MWT) were performed on patients at baseline. The sample was grouped into high and low levels at the median of TL perfusion, ipsilateral nontarget lobe (INL) perfusion, and heterogeneity index (HI). These groups were analyzed for association with changes in outcome parameters from baseline to 3 months follow-up. Compared to baseline, patients showed significant improvements in PFT, SGRQ, and 6MWT (all P<=0.001). TL perfusion was not associated with changes in the outcome. High INL perfusion was significantly associated with increases in 6MWT (P=0.014), and high HI was associated with increases in forced expiratory volume in 1 second (FEV1), (P=0.012). Likewise, there were significant correlations for INL perfusion and improvement of 6MWT (r=0.35, P=0.03) and for HI and improvement in FEV1 (r=0.45, P=0.001). This study reveals new attributes that associate with positive outcomes for patient selection prior to ELVR. Patients with high perfusions in INL demonstrated greater improvements in 6MWT, while patients with high HI were more likely to respond in FEV1. PMID- 27354784 TI - Impact of combined pulmonary fibrosis and emphysema on surgical complications and long-term survival in patients undergoing surgery for non-small-cell lung cancer. AB - PURPOSE: The outcome of radical surgery for lung cancer was investigated in patients with combined pulmonary fibrosis and emphysema (CPFE). METHODS: A retrospective chart review involved 250 patients with lung cancer who underwent pulmonary resection at Tokyo Women's Medical University Yachiyo Medical Center between 2008 and 2012. Based on the status of nontumor-bearing lung evaluated by preoperative computed tomography (CT), the patients were divided into normal, emphysema, interstitial pneumonia (IP), and CPFE groups, and their clinical characteristics and surgical outcome were analyzed. RESULTS: The normal, emphysema, IP, and CPFE groups comprised 124 (49.6%), 108 (43.2%), seven (2.8%), and eleven (4.4%) patients, respectively. The 5-year survival rate of the CPFE group (18.7%) was significantly lower than that of the normal (77.5%) and emphysema groups (67.1%) (P<0.0001 and P=0.0027, respectively) but equivalent to that of the IP group (44.4%) (P=0.2928). In a subset analysis of cancer stage, the 5-year overall survival rate of the CPFE group in stage I (n=8, 21.4%) was also lower than that of the normal group and emphysema group in stage I (n=91, 84.9% and n=70, 81.1%; P<0.0001 and P<0.0001, respectively). During entire observation period, the CPFE group was more likely to die of respiratory failure (27.2%) compared with the normal and emphysema groups (P<0.0001). Multivariate analysis of prognostic factors using Cox proportional hazard model identified CPFE as an independent risk factor (P=0.009). CONCLUSION: CPFE patients have a poorer prognosis than those with emphysema alone or with normal lung on CT finding. The intensive evaluation of preoperative CT images is important, and radical surgery for lung cancer should be decided carefully when patients concomitantly harbor CPFE, because of unfavorable prognosis. PMID- 27354785 TI - Impact of mild exacerbation on COPD symptoms in a Japanese cohort. AB - BACKGROUND: Patients with COPD might not report mild exacerbation. The frequency, risk factors, and impact of mild exacerbation on COPD status are unknown. OBJECTIVES: The present study was performed to compare features between mild exacerbation and moderate or severe exacerbation in Japanese patients with COPD. PATIENTS AND METHODS: An observational COPD cohort was designed at Keio University and affiliated hospitals to prospectively investigate the management of COPD comorbidities. This study analyzes data only from patients with COPD who had completed annual examinations and questionnaires over a period of 2 years (n=311). RESULTS: Among 59 patients with mild exacerbations during the first year, 32.2% also experienced only mild exacerbations in the second year. Among 60 patients with moderate or severe exacerbations during the first year, 40% also had the same severity of exacerbation during the second year. Findings of the COPD assessment test and the symptom component of the St George's Respiratory Questionnaire at steady state were worse in patients with mild exacerbations than in those who were exacerbation free during the 2-year study period, although the severity of the ratio of predicted forced expiratory volume in 1 second did not differ between them. Severe airflow limitation (the ratio of predicted forced expiratory volume in 1 second <50%) and experience of mild exacerbations independently advanced the likelihood of an elevated COPD assessment test score to >=2 per year. CONCLUSION: The severity of COPD exacerbation seemed to be temporally stable over 2 years, and even mild exacerbations adversely impacted the health-related quality of life of patients with COPD. PMID- 27354786 TI - alpha1-Antitrypsin reduces rhinovirus infection in primary human airway epithelial cells exposed to cigarette smoke. AB - Human rhinovirus (HRV) infections target airway epithelium and are the leading cause of acute exacerbations of COPD. Cigarette smoke (CS) increases the severity of viral infections, but there is no effective therapy for HRV infection. We determined whether alpha1-antitrypsin (A1AT) reduces HRV-16 infection in CS exposed primary human airway epithelial cells. Brushed bronchial epithelial cells from normal subjects and patients diagnosed with COPD were cultured at air-liquid interface to induce mucociliary differentiation. These cells were treated with A1AT or bovine serum albumin for 2 hours and then exposed to air or whole cigarette smoke (WCS) with or without HRV-16 (5*10(4) 50% Tissue Culture Infective Dose [TCID50]/transwell) infection for 24 hours. WCS exposure significantly increased viral load by an average of fivefold and decreased the expression of antiviral genes interferon-lambda1, OAS1, and MX1. When A1AT was added to WCS-exposed cells, viral load significantly decreased by an average of 29-fold. HRV-16 infection significantly increased HRV-16 receptor intercellular adhesion molecule-1 messenger RNA expression in air-exposed cells, which was decreased by A1AT. A1AT-mediated reduction of viral load was not accompanied by increased epithelial antiviral gene expression or by inhibiting the activity of 3C protease involved in viral replication or maturation. Our findings demonstrate that A1AT treatment prevents a WCS-induced increase in viral load and for the first time suggest a therapeutic effect of A1AT on HRV infection. PMID- 27354787 TI - Depression symptoms reduce physical activity in COPD patients: a prospective multicenter study. AB - BACKGROUND: The role of anxiety and depression in the physical activity (PA) of patients with COPD is controversial. We prospectively assessed the effect of symptoms of anxiety and depression on PA in COPD patients. METHODS: We evaluated anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), PA (Dynaport((r)) accelerometer), and other relevant characteristics in 220 COPD patients from five European countries at baseline and at 6 and 12 months of follow-up. HADS score was categorized as: no symptoms (score 0-7), suggested (8 10), and probable (>11) anxiety or depression. We estimated the association between anxiety and depression at t (baseline and 6 months) and PA at t+1 (6 and 12 months) using regression models with a repeated measures approach. RESULTS: Patients had a mean (standard deviation) age of 67 (8) years, forced expiratory volume in 1 second 57 (20)% predicted. At baseline, the prevalence of probable anxiety and depression was 10% and 5%, respectively. In multivariable models adjusted by confounders and previous PA, patients performed 81 fewer steps/day (95% confidence interval, -149 to -12, P=0.02) per extra point in HADS-depression score. HADS-anxiety symptoms were not associated with PA. CONCLUSION: In COPD patients, symptoms of depression are prospectively associated with a measurable reduction in PA 6 months later. PMID- 27354788 TI - Acute hematologic, hepatologic, and nephrologic changes after intraperitoneal injections of 18 nm gold nanoparticles in hamsters. AB - In vivo responses to gold nanoparticles (GNPs) vary not only according to the size, shape, surface charge, and capping agent of GNPs but also according to the animal model, the route of administration, and the exposure frequency and duration. We illustrate here the changes in some hematologic parameters, in the hepatic and renal functions, and in the histopathology of solid organs after multiple intraperitoneal injections of 18 nm GNPs in adult male Syrian golden hamsters. We scored the histopathological changes in the liver and kidneys to grade the deleterious effects. Multiple intraperitoneal injections of 18 nm GNPs in hamsters were nonlethal in the short term but resulted in macrocytosis and hypochromasia, leukocytosis, neutrophilia, lymphocytosis, and monocytosis. The hepatic and renal functions showed nonsignificant changes; however, histopathological examination showed hepatic and renal alterations ranging from mild to marked degeneration, with occasional necrosis of hepatocytes and tubular epithelium. PMID- 27354789 TI - Fast and safe fabrication of a free-standing chitosan/alginate nanomembrane to promote stem cell delivery and wound healing. AB - Polymeric ultrathin membranes that are compatible with cells offer tremendous advantages for tissue engineering. In this article, we report a free-standing nanomembrane that was developed using a layer-by-layer self-assembly technique with a safe and sacrificial substrate method. After ionization, two oppositely charged polyelectrolytes, alginate and chitosan, were alternately deposited on a substrate of a solidified gelatin block to form an ultrathin nanomembrane. The space between the two adjacent layers was ~200 nm. The thickness of the nanomembrane was proportional to the number of layers. The temperature-sensitive gelatin gel served as a sacrificial template at 37 degrees C. The free-standing nanomembrane promoted bone marrow stem cell adhesion and proliferation. Fluorescence-activated cell sorting was used to analyze green-fluorescent-protein positive mesenchymal stem cells from the wounds, which showed a significantly high survival and proliferation from the nanomembrane when cells were transplanted to mouse dorsal skin that had a full-thickness burn. The bone-marrow stem-cell-loaded nanomembrane also accelerated wound contraction and epidermalization. Therefore, this methodology provides a fast and facile approach to construct free-standing ultrathin scaffolds for tissue engineering. The biocompatibility and free-standing nature of the fabricated nanomembrane may be particularly useful for stem cell delivery and wound healing. PMID- 27354790 TI - Delivery of dexamethasone from bioactive nanofiber matrices stimulates odontogenesis of human dental pulp cells through integrin/BMP/mTOR signaling pathways. AB - Therapeutically relevant design of scaffolds is of special importance in the repair and regeneration of tissues including dentin and pulp. Here we exploit nanofiber matrices that incorporate bioactive glass nanoparticles (BGNs) and deliver the odontogenic drug dexamethasone (DEX) to stimulate the odontogenic differentiation of human dental pulp cells (HDPCs). DEX molecules were first loaded onto the BGN, and then the DEX-BGN complex was incorporated within the biopolymer nanofiber matrix through electrospinning. The release of DEX continued over a month, showing a slow releasing profile. HDPCs cultured on the DEX releasing BGN matrices were viable, proliferating well up to 14 days. The odontogenic differentiation, as assessed by alkaline phosphatase activity, mRNA expression of genes, and mineralization, was significantly stimulated on the matrices incorporating BGN and further on those releasing DEX. The DEX-releasing BGN matrices highly upregulated the expression of the integrin subsets alpha1, alpha5, and beta3 as well as integrin downstream signaling molecules, including focal adhesion kinase (FAK), Paxillin, and RhoA, and activated bone morphogenetic protein mRNA and phosphorylation of Smad1/5/8. Furthermore, the DEX-releasing BGN matrices stimulated Akt and mammalian target of rapamycin (mTOR), which was proven by the inhibition study. Collectively, the designed therapeutic nanofiber matrices that incorporate BGN and deliver DEX were demonstrated to promote odontogenesis of HDPCs, and the integrins, bone morphogenetic protein, and mTOR signaling pathways are proposed to be the possible molecular mechanisms. While further in vivo studies are still needed, the DEX-releasing bioactive scaffolds are considered as a potential therapeutic nanomatrix for regenerative endodontics and tissue engineering. PMID- 27354791 TI - Intratracheal instillation of ethyl pyruvate nanoparticles prevents the development of shunt-flow-induced pulmonary arterial hypertension in a rat model. AB - PURPOSE: To investigate whether inhalation of ethyl pyruvate (EP) encapsulated with poly(ethylene glycol)-block-lactide/glycolide copolymer nanoparticles (EP NPs) can prevent the development of shunt-flow-induced hyperkinetic pulmonary arterial hypertension (PAH) in a rat model. MATERIALS AND METHODS: Rats were separated into five groups: blank (ie, no treatment after shunt flow), normal control (ie, no shunt flow or treatment), EP-NP instillation, EP-only instillation, and vehicle. The animals received intratracheal instillation of EP NPs or other treatments immediately after a shunt flow, and treatment continued weekly until the end of the experiment. Hemodynamic data were recorded, pulmonary arterial remodeling was assessed, and levels of inflammatory mediators and ET1 expression in the lung and serum were analyzed. In addition, retention of EP in the lungs of rats in the EP-NP and EP-only groups was measured using high performance liquid chromatography. RESULTS: After 12 weeks, hemodynamic abnormalities and pulmonary arterial remodeling were improved in the EP-NP instillation group, compared with the blank, EP-only, and vehicle groups (P<0.05). In addition, the EP-NP group showed significantly decreased levels of HMGB1, IL-6, TNFalpha, reactive oxygen species, and ET1 in the lung during PAH development (P<0.05). Furthermore, EP-NP instillation was associated with reduced serum levels of inflammatory factors and ET1. High-performance liquid chromatography measurement indicated that EP retention was greater in the lungs of the EP-NP group than in the EP-only group. CONCLUSION: EP-NP instillation attenuated inflammation and prevented pulmonary arterial remodeling during the development of PAH induced by shunt flow. In the future, EP-NP delivery into the lung might provide a novel approach for preventing PAH. PMID- 27354792 TI - Design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells. AB - The aim of the present work was to develop and optimize surface-functionalized solid lipid nanoparticles (SLNs) for improvement of the therapeutic index of dapsone (DAP), with the application of a design of experiments. The formulation was designed to target intestinal microfold (M-cells) as a strategy to increase internalization of the drug by the infected macrophages. DAP-loaded SLNs and mannosylated SLNs (M-SLNs) were successfully developed by hot ultrasonication method employing a three-level, three-factor Box-Behnken design, after the preformulation study was carried out with different lipids. All the formulations were systematically characterized regarding their diameter, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, and loading capacity. They were also subjected to morphological studies using transmission electron microscopy, in vitro release study, infrared analysis (Fourier transform infrared spectroscopy), calorimetry studies (differential scanning calorimetry), and stability studies. The diameter of SLNs, SLN-DAP, M-SLNs, and M-SLN-DAP was approximately 300 nm and the obtained PDI was <0.2, confirming uniform populations. Entrapment efficiency and loading capacity were approximately 50% and 12%, respectively. Transmission electron microscopy showed spherical shape and nonaggregated nanoparticles. Fourier transform infrared spectroscopy was used to confirm the success of mannose coating process though Schiff's base formation. The variation of the ZP between uncoated (approximately -30 mV) and mannosylated formulations (approximately +60 mV) also confirmed the successful coating process. A decrease in the enthalpy and broadening of the lipid melting peaks of the differential scanning calorimetry thermograms are consistent with the nanostructure of the SLNs. Moreover, the drug release was pH-sensitive, with a faster drug release at acidic pH than at neutral pH. Storage stability for the formulations for at least 8 weeks is expected, since they maintain the original characteristics of diameter, PDI, and ZP. These results pose a strong argument that the developed formulations can be explored as a promising carrier for treating leprosy with an innovative approach to target DAP directly to M-cells. PMID- 27354793 TI - Magnetic micro/nanoparticle flocculation-based signal amplification for biosensing. AB - We report a time and cost efficient signal amplification method for biosensors employing magnetic particles. In this method, magnetic particles in an applied external magnetic field form magnetic dipoles, interact with each other, and accumulate along the magnetic field lines. This magnetic interaction does not need any biomolecular coating for binding and can be controlled with the strength of the applied magnetic field. The accumulation can be used to amplify the corresponding pixel area that is obtained from an image of a single magnetic particle. An application of the method to the Escherichia coli 0157:H7 bacteria samples is demonstrated in order to show the potential of the approach. A minimum of threefold to a maximum of 60-fold amplification is reached from a single bacteria cell under a magnetic field of 20 mT. PMID- 27354794 TI - Peptide-coated gold nanoparticles for modulation of angiogenesis in vivo. AB - In this work, peptides designed to selectively interact with cellular receptors involved in the regulation of angiogenesis were anchored to oligo-ethylene glycol capped gold nanoparticles (AuNPs) and used to evaluate the modulation of vascular development using an ex ovo chick chorioallantoic membrane assay. These nanoparticles alter the balance between naturally secreted pro- and antiangiogenic factors, under various biological conditions, without causing toxicity. Exposure of chorioallantoic membranes to AuNP-peptide activators of angiogenesis accelerated the formation of new arterioles when compared to scrambled peptide-coated nanoparticles. On the other hand, antiangiogenic AuNP peptide conjugates were able to selectively inhibit angiogenesis in vivo. We demonstrated that AuNP vectorization is crucial for enhancing the effect of active peptides. Our data showed for the first time the effective control of activation or inhibition of blood vessel formation in chick embryo via AuNP-based formulations suitable for the selective modulation of angiogenesis, which is of paramount importance in applications where promotion of vascular growth is desirable (eg, wound healing) or ought to be contravened, as in cancer development. PMID- 27354795 TI - XanoMatrix surfaces as scaffolds for mesenchymal stem cell culture and growth. AB - Stem cells are being widely investigated for a wide variety of applications in tissue engineering due to their ability to differentiate into a number of cells such as neurons, osteoblasts, and fibroblasts. This ability of stem cells to differentiate into different types of cells is greatly based on mechanical and chemical cues received from their three-dimensional environments. All organs are formed by a number of cells linked together via an extracellular matrix (ECM). The ECM is a complex network of proteins and carbohydrates, which occupies intercellular spaces and regulates cellular activity by controlling cell adhesion, migration, proliferation, and differentiation. The ECM is composed of two main types of macromolecules, namely, polysaccharide glycosaminoglycans, which are covalently attached to proteins in the form of proteoglycans and fibrous proteins belonging to two functional groups, structural (collagen and elastin) and adhesive (fibronectin, laminin, vitronectin, etc). Tissue engineering is a multidisciplinary field that aims to develop biomimetic scaffolds that emulate properties of the ECM to help repair or regenerate diseased or damaged tissue. This study introduces one of these matrices, XanoMatrix, as an optimal scaffold for tissue engineering applications, in particular, for stem cell research, based on its composition, nanofibrous structure, and porosity. Results of this study suggest that XanoMatrix scaffolds are promising for stem cell tissue engineering applications and as improved cell culture inserts for studying stem cell functions (compared to traditional Corning and Falcon cell culture plates) and, thus, should be further studied. PMID- 27354796 TI - Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo. AB - Triptolide (TP) displays a strong immunosuppression function in immune-mediated diseases, especially in the treatment of rheumatoid arthritis. However, in addition to its medical and health-related functions, TP also exhibits diverse pharmacological side effects, for instance, liver and kidney toxicity and myelosuppression. In order to reduce the side effects, a nano drug carrier system (gamma-PGA-l-PAE-TP [PPT]), in which TP was loaded by a poly-gamma-glutamic acid grafted l-phenylalanine ethylester copolymer, was developed. PPT was characterized by photon scattering correlation spectroscopy and transmission electron microscopy, which demonstrated that the average diameter of the drug carrier system is 98+/-15 nm, the polydispersity index is 0.18, the zeta potential is -35 mV, and the TP encapsulation efficiency is 48.6% with a controlled release manner. The methylthiazolyldiphenyl-tetrazolium bromide assay and flow cytometry revealed that PPT could decrease toxicity and apoptosis induced by free TP on RAW264.7 cells, respectively. The detection of reactive oxygen species showed that PPT could decrease the cellular reactive oxygen species induced by TP. Compared with the free TP-treated group, PPT improved the survival rate of the mice (P<0.01) and had no side effects or toxic effects on the thymus index (P>0.05) and spleen index (P>0.05). The blood biochemical indexes revealed that PPT did not cause much damage to the kidney (blood urea nitrogen and creatinine), liver (serum alanine aminotransferase and aspartate aminotransferase), or blood cells (P>0.05). Meanwhile, hematoxylin and eosin staining and terminal-deoxynucleotidyl transferase dUTP nick-end labeling staining indicated that PPT reduced the damage of free TP on the liver, kidney, and spleen. Our results demonstrated that PPT reduced free TP toxicity in vitro and in vivo and that it is a promising fundamental drug delivery system for rheumatoid arthritis treatment. PMID- 27354797 TI - In vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine)-based nanoparticles. AB - A major challenge in neuronal gene therapy is to achieve safe, efficient, and minimally invasive transgene delivery to neurons. In this study, we report the use of a nonviral neurotropic poly(ethylene imine)-based nanoparticle that is capable of mediating neuron-specific transfection upon a subcutaneous injection. Nanoparticles were targeted to peripheral neurons by using the nontoxic carboxylic fragment of tetanus toxin (HC), which, besides being neurotropic, is capable of being retrogradely transported from neuron terminals to the cell bodies. Nontargeted particles and naked plasmid DNA were used as control. Five days after treatment by subcutaneous injection in the footpad of Wistar rats, it was observed that 56% and 64% of L4 and L5 dorsal root ganglia neurons, respectively, were expressing the reporter protein. The delivery mediated by HC functionalized nanoparticles spatially limited the transgene expression, in comparison with the controls. Histological examination revealed no significant adverse effects in the use of the proposed delivery system. These findings demonstrate the feasibility and safety of the developed neurotropic nanoparticles for the minimally invasive delivery of genes to the peripheral nervous system, opening new avenues for the application of gene therapy strategies in the treatment of peripheral neuropathies. PMID- 27354798 TI - Elimination of the biphasic pharmacodynamics of 15d-PGJ2 by controlling its release from a nanoemulsion. AB - 15-Deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) has a dual action of stimulating anti-inflammation and anti-proliferation when exogenously administered at high doses. However, at lower doses, it can be toxic inducing opposite actions, ie, stimulation of both inflammation and cell proliferation. This biphasic phenomenon of 15d-PGJ2 is believed to be due to its multitarget behavior. In this study, we provide a strategy for controlling such biphasic pharmacodynamics by separating its dual actions while retaining the beneficial one by using a nanoemulsion (NE). The 15d-PGJ2 was encapsulated in the NE composed of triolein/distearoyl phosphatidylcholine/Tween 80 at a high encapsulation ratio (>83%). Furthermore, NE enhanced drug retention by slowing down its release rate, which was, unconventionally, inversely dependent on the total surface area of the NE system. Next, focusing on the biphasic effect on cell proliferation, we found that the 15d-PGJ2-loaded slow-release NE showed only a dose-dependent inhibition of the viability of a mouse macrophage cell line, RAW264.7, although a fast-release NE as well as free 15d-PGJ2 exerted a biphasic effect. The observed slow-release kinetics are believed to be responsible for elimination of the biphasic pharmacodynamics of 15d-PGJ2 mainly for two reasons: 1) a high proportion of 15d PGJ2 that is retained in the NE was delivered to the cytosol, where proapoptotic targets are located and 2) 15d-PGJ2 was able to bypass cell membrane-associated targets that lead to the induction of cellular proliferation. Collectively, our strategy of eliminating the 15d-PGJ2-induced biphasic pharmacodynamics was based on the delivery of 15d-PGJ2 to its desired site of action, excluding undesired sites, on a subcellular level. PMID- 27354800 TI - Evaluation of oxidative response and tissular damage in rat lungs exposed to silica-coated gold nanoparticles under static magnetic fields. AB - The purpose of our study was the evaluation of toxicological effects of silica coated gold nanoparticles (GNPs) and static magnetic fields (SMFs; 128 mT) exposure in rat lungs. Animals received a single injection of GNPs (1,100 ug/kg, 100 nm, intraperitoneally) and were exposed to SMFs, over 14 days (1 h/day). Results showed that GNPs treatment induced a hyperplasia of bronchus-associated lymphoid tissue. Fluorescence microscopy images showed that red fluorescence signal was detected in rat lungs after 2 weeks from the single injection of GNPs. Oxidative response study showed that GNPs exposure increased malondialdehyde level and decreased CuZn-superoxide dismutase, catalase, and glutathione peroxidase activities in rat lungs. Furthermore, the histopathological study showed that combined effects of GNPs and SMFs led to more tissular damages in rat lungs in comparison with GNPs-treated rats. Interestingly, intensity of red fluorescence signal was enhanced after exposure to SMFs indicating a higher accumulation of GNPs in rat lungs under magnetic environment. Moreover, rats coexposed to GNPs and SMFs showed an increased malondialdehyde level, a fall of CuZn-superoxide dismutase, catalase, and glutathione peroxidase activities in comparison with GNPs-treated group. Hence, SMFs exposure increased the accumulation of GNPs in rat lungs and led to more toxic effects of these nanocomplexes. PMID- 27354799 TI - From micro- to nanostructured implantable device for local anesthetic delivery. AB - Local anesthetics block the transmission of painful stimuli to the brain by acting on ion channels of nociceptor fibers, and find application in the management of acute and chronic pain. Despite the key role they play in modern medicine, their cardio and neurotoxicity (together with their short half-life) stress the need for developing implantable devices for tailored local drug release, with the aim of counterbalancing their side effects and prolonging their pharmacological activity. This review discusses the evolution of the physical forms of local anesthetic delivery systems during the past decades. Depending on the use of different biocompatible materials (degradable polyesters, thermosensitive hydrogels, and liposomes and hydrogels from natural polymers) and manufacturing processes, these systems can be classified as films or micro- or nanostructured devices. We analyze and summarize the production techniques according to this classification, focusing on their relative advantages and disadvantages. The most relevant trend reported in this work highlights the effort of moving from microstructured to nanostructured systems, with the aim of reaching a scale comparable to the biological environment. Improved intracellular penetration compared to microstructured systems, indeed, provides specific drug absorption into the targeted tissue and can lead to an enhancement of its bioavailability and retention time. Nanostructured systems are realized by the modification of existing manufacturing processes (interfacial deposition and nanoprecipitation for degradable polyester particles and high- or low-temperature homogenization for liposomes) or development of novel strategies (electrospun matrices and nanogels). The high surface-to-volume ratio that characterizes nanostructured devices often leads to a burst drug release. This drawback needs to be addressed to fully exploit the advantage of the interaction between the target tissues and the drug: possible strategies could involve specific binding between the drug and the material chosen for the device, and a multiscale approach to reach a tailored, prolonged drug release. PMID- 27354802 TI - Cognitive behavioral therapy for depression in Japanese Parkinson's disease patients: a pilot study. AB - OBJECTIVES: This study evaluated the feasibility of cognitive behavioral therapy (CBT) for Japanese Parkinson's disease (PD) patients with depression. To increase cultural acceptability, we developed the CBT program using manga, a type of Japanese comic novel. METHODS: Participants included 19 non-demented PD patients who had depressive symptoms (GRID-Hamilton Rating Scale for Depression score >=8). A CBT program comprising six sessions was individually administered. We evaluated the feasibility and safety of the CBT program in terms of the dropout rate and occurrence of adverse events. The primary outcome was depressive symptom reduction in the GRID-Hamilton Rating Scale for Depression upon completion of CBT. Secondary outcomes included changes in the self-report measures of depression (Beck Depression Inventory-II, Hospital Anxiety and Depression Scale Depression), anxiety (Hospital Anxiety and Depression Scale-Anxiety, State and Trait Anxiety Inventory, Overall Anxiety Severity and Impairment Scale), functional impairment, and quality of life (Medical Outcomes Study 36-Item Short Form Health Survey). RESULTS: Of the 19 participants (mean age =63.8 years, standard deviation [SD] =9.9 years; mean Hohen-Yahr score =1.7, SD =0.8), one patient (5%) withdrew. No severe adverse event was observed. The patients reported significant improvements in depression (Hedges' g =-1.02, 95% confidence interval =-1.62 to -0.39). The effects were maintained over a 3-month follow-up period. Most of the secondary outcome measurements showed a small-to-moderate but nonsignificant effect size from baseline to post-intervention. CONCLUSION: This study provides preliminary evidence that CBT is feasible among Japanese PD patients with depression. Similar approaches may be effective for people with PD from other cultural backgrounds. The results warrant replication in a randomized controlled trial. PMID- 27354801 TI - Biodegradable micelles enhance the antiglioma activity of curcumin in vitro and in vivo. AB - Curcumin (Cur), a natural polyphenol of Curcuma longa, has been recently reported to possess antitumor activities. However, due to its poor aqueous solubility and low biological availability, the clinical application of Cur is quite limited. The encapsulation of hydrophobic drugs into nanoparticles is an effective way to improve their pharmaceutical activities. In this research, nanomicelles loaded with Cur were formulated by a self-assembly method with biodegradable monomethoxy poly(ethylene glycol)-poly(lactide) copolymers (MPEG-PLAs). After encapsulation, the cellular uptake was increased and Cur could be released from MPEG-PLA micelles in a sustained manner. The Cur-loaded MPEG-PLA micelles (Cur/MPEG-PLA micelles) exhibited an enhanced toxicity on C6 and U251 glioma cells and induced more apoptosis on C6 glioma cells compared with free Cur. Moreover, the therapy efficiency of Cur/MPEG-PLA micelles was evaluated at length on a nude mouse model bearing glioma. The Cur/MPEG-PLA micelles were more effective on suppressing tumor growth compared with free Cur, which indicated that Cur/MPEG-PLA micelles improved the antiglioma activity of Cur in vivo. The results of immunohistochemical and immunofluorescent analysis indicated that the induction of apoptosis, antiangiogenesis, and inhibition of cell proliferation may contribute to the improvement in antiglioma effects. Our data suggested that Cur/MPEG-PLA may have potential clinic applications in glioma therapy. PMID- 27354803 TI - Investigating analgesic and psychological factors associated with risk of postpartum depression development: a case-control study. AB - AIM: The aim of this study was to investigate the role of peripartum analgesic and psychological factors that may be related to postpartum depression (PPD). METHODS: This case-control study was conducted in pregnant females who delivered at KK Women's and Children's Hospital from November 2010 to October 2013 and had postpartum psychological assessment. Demographic, medical, and postpartum psychological status assessments, intrapartum data including method of induction of labor, mode of labor analgesia, duration of first and second stages of labor, mode of delivery, and pain intensity on hospital admission and after delivery were collected. PPD was assessed using the Edinburgh Postnatal Depression Scale and clinical assessment by the psychiatrist. RESULTS: There were 62 cases of PPD and 417 controls after childbirth within 4-8 weeks. The odds of PPD was significantly lower (33 of 329 [10.0%]) in females who received epidural analgesia for labor compared with those who chose nonepidural analgesia (29 of 150 [19.3%]) ([odds ratio] 0.47 (0.27-0.8), P=0.0078). The multivariate analysis showed that absence of labor epidural analgesia, increasing age, family history of depression, history of depression, and previous history of PPD were independent risk factors for development of PPD. CONCLUSION: The absence of labor epidural analgesia remained as an independent risk factor for development of PPD when adjusted for psychiatric predictors of PPD such as history of depression or PPD and family history of depression. PMID- 27354804 TI - Randomized controlled trials - a matter of design. AB - Randomized controlled trials (RCTs) are the hallmark of evidence-based medicine and form the basis for translating research data into clinical practice. This review summarizes commonly applied designs and quality indicators of RCTs to provide guidance in interpreting and critically evaluating clinical research data. It further reflects on the principle of equipoise and its practical applicability to clinical science with an emphasis on critical care and neurological research. We performed a review of educational material, review articles, methodological studies, and published clinical trials using the databases MEDLINE, PubMed, and ClinicalTrials.gov. The most relevant recommendations regarding design, conduction, and reporting of RCTs may include the following: 1) clinically relevant end points should be defined a priori, and an unbiased analysis and report of the study results should be warranted, 2) both significant and nonsignificant results should be objectively reported and published, 3) structured study design and performance as indicated in the Consolidated Standards of Reporting Trials statement should be employed as well as registration in a public trial database, 4) potential conflicts of interest and funding sources should be disclaimed in study report or publication, and 5) in the comparison of experimental treatment with standard care, preplanned interim analyses during an ongoing RCT can aid in maintaining clinical equipoise by assessing benefit, harm, or futility, thus allowing decision on continuation or termination of the trial. PMID- 27354805 TI - Bilateral internal carotid artery dissection associated with prior syphilis: a case report and review of the literature. AB - Bilateral internal carotid artery dissection is a rare entity, and its presentation may include cerebral ischemia. We describe the case of a 69-year-old man with ischemic stroke and radiological evidence of intimal flap of both internal carotid arteries suggestive for dissection. During the hospitalization, our patient was found positive for a previous syphilis infection. We conducted a review of the literature, with evidence of a few cases of ischemic stroke presumably related to a prior syphilis. The absence of major cardiovascular risk factors in our patient leads us to believe that an etiopathogenetic link may exist between these two conditions. PMID- 27354806 TI - Clinical usefulness of mepolizumab in severe eosinophilic asthma. AB - Asthma is a chronic inflammatory disorder of the airways with variable clinical severity from very mild and occasional symptoms to recurrent critical exacerbations, at risk of fatal or near-fatal outcome, in a small percentage of patients. Within the different inflammatory cascades involved in asthma, eosinophils play a central role in the pathogenesis and largely influence disease severity. Interleukin-5 (IL-5) is the main cytokine controlling eosinophil activity and proliferation at the site of inflammation. Mepolizumab was the first biological humanized anti-IL-5 monoclonal antibody tested in randomized clinical trials on eosinophilic asthma and other eosinophilic diseases. On the basis of several positive clinical efficacy data, it has recently been approved by the US Food and Drug Administration for the treatment of severe eosinophilic asthma. Unfortunately, high costs are at present a critical issue. Future studies will probably help in the correct selection of a potential "responder phenotype", allowing the prescription of this promising therapy to appropriate patients and best define cost-effectiveness issues. PMID- 27354808 TI - A case of gait disturbance caused by low-dose gabapentin. AB - Gabapentin, an anticonvulsant agent, is now often used for the treatment of neuropathic pain all over the world. It is unclear whether the combined use of gabapentin, sodium valproate, and flunitrazepam results in enhancement of the side effect, a gait disturbance. A 60-year-old man was taking oral sodium valproate for symptomatic epilepsy after a brain contusion and flunitrazepam to relieve insomnia. Oral gabapentin therapy was started for suspected neuropathic pain. Although the initial dose of oral gabapentin (200 mg) relieved the pain, the lower extremities became weak, resulting in a gait disturbance. The therapy was restarted with a halved dose, and this resolved the gait disturbance and relieved the pain. PMID- 27354807 TI - Management of chemotherapy-induced nausea and vomiting by risk profile: role of netupitant/palonosetron. AB - As recommended by most recent antiemetic guidelines, the optimal prophylaxis of chemotherapy-induced nausea and vomiting (CINV) requires the combination of 5-HT3 receptor antagonist (RA) with an NK1-RA. Moreover, the major predictors of acute and delayed CINV include: young age, female sex, platinum- or anthracycline-based chemotherapy, nondrinker status, emesis in the earlier cycles of chemotherapy, and previous history of motion/morning sickness. Despite improved knowledge of the pathophysiology of CINV and advances in the availability of active antiemetics, an inconsistent compliance with their use has been reported, thereby resulting in suboptimal control of CINV in several cases. In this scenario, a new anti-emetic drug is now available, which seems to be able to guarantee better prophylaxis of CINV and improvement of adherence to guidelines. In fact, netupitant/palonosetron (NEPA) is a ready-to-use single oral capsule, combining an NK1-RA (netupitant) and a 5-HT3-RA (palonosetron), which is to be taken 1 hour before the administration of chemotherapy, ensuring the coverage from CINV for 5 days. We reviewed the role of NEPA in patients at high risk of CINV receiving highly emetogenic chemotherapy. In these patients, NEPA plus dexamethasone, as compared to standard treatments, achieved superior efficacy in all primary and secondary end points during the acute, delayed, and overall phases, including nausea assessment. Moreover, these results were also achieved in female patients receiving anthracycline plus cyclophosphamide-based chemotherapy. NEPA represents a real step forward in the prophylaxis of CINV. PMID- 27354809 TI - Clinical efficacy of dalbavancin for the treatment of acute bacterial skin and skin structure infections (ABSSSI). AB - Acute bacterial skin and skin structure infections (ABSSSI) are a common disease causing patients to seek treatment through the health care system. With the continued increase of drug-resistant bacterial pathogens, these infections are becoming more difficult to successfully cure. Lipoglycopeptides have unique properties that allow the drug to remain active toward both common and challenging pathogens at the infected site for lengthy periods of time. Dalbavancin, a new lipoglycopeptide, provides two unique dosing regimens for the treatment of ABSSSI. The original regimen of 1,000 mg intravenous infusion followed by a 500 mg intravenous infusion after a week has been shown as safe and effective in multiple, randomized noninferiority trials. These studies also demonstrated that dalbavancin was similar to standard regimens in terms of both safety and tolerability. Recently a single 1,500 mg dose was demonstrated to be equivalent to the dalbavancin two-dose regimen for treating ABSSSI. With the introduction of dalbavancin, clinicians have the option to provide an intravenous antimicrobial agent shown to be as effective as traditional therapies, without requiring admission into the hospitals or prescribing a medication which may not be utilized optimally. Further understanding of dalbavancin and its unusual properties can provide unique treatment situations with potential benefits for both the patient and the overall health care system, which should be further explored. PMID- 27354810 TI - Pazopanib in the management of advanced soft tissue sarcomas. AB - Therapy of soft tissue sarcomas represents an area of significant unmet need in oncology. Angiogenesis has been explored as a potential target both preclinically and clinically, with suggestions of activity. Pazopanib is a multitargeted tyrosine kinase inhibitor with prominent antiangiogenic effects. In a Phase II study, pazopanib demonstrated activity in strata enrolling patients with leiomyosarcomas, synovial sarcomas, or other sarcomas but not those enrolling adipocytic sarcomas. PALETTE, the pivotal Phase III trial, demonstrated improved progression-free survival versus placebo in pazopanib-treated patients previously treated for advanced soft tissue sarcomas. No survival benefit was observed, and adipocytic sarcomas were excluded. Health-related quality-of-life assessments indicated significant decrements in several areas affected by pazopanib toxicities, but no global deterioration. Cost-effectiveness analyses indicate that pazopanib therapy may or may not be cost-effective in different geographic settings. Pazopanib provides important proof-of-concept for antiangiogenic therapy in soft tissue sarcomas. Its use can be improved by further biological studies of its activity profile in sarcomas, studies of biological rational combinations, and clinicopathologic/biological correlative studies of activity to allow better drug targeting. PMID- 27354811 TI - Treatment of patients with chronic thrombo embolic pulmonary hypertension: focus on riociguat. AB - Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease of the pulmonary vascular bed that is characterized by elevations in the mean pulmonary artery pressure in the setting of perfusion defects on ventilation-perfusion scan, and subsequently confirmed by pulmonary angiography. CTEPH, or World Health Organization (WHO) group 4 pulmonary hypertension, is a result of unresolved thromboembolic obstruction in the pulmonary arteries. Pulmonary endarterectomy (PEA) is the treatment of choice for CTEPH as it is a potentially curative therapy. However, up to one-third of patients are not candidates for the surgery, either due to distal and inaccessible nature of the lesions or comorbid conditions. Due to remodeling that occurs in nonobstructed pulmonary vessels, a portion of patients who have undergone PEA have residual CTEPH after the procedure, attributable to high shear stress prior to PEA. This phenomenon has led to the understanding of a so-called "two-compartment model" of CTEPH, opening the door to pharmacologic treatment strategies. In 2013, riociguat, a soluble guanylate cyclase stimulator, was approved in the US and Europe for the treatment of inoperable or persistent/recurrent CTEPH. This article reviews the current management of CTEPH with a focus on riociguat. PMID- 27354813 TI - GPR30 decreases with vascular aging and promotes vascular smooth muscle cells maintaining differentiated phenotype and suppressing migration via activation of ERK1/2. AB - Estrogen receptors, including classic nuclear receptors ERalpha, ERbeta, and membrane receptor GPR30, are expressed in vascular tissues and exert protective actions in vascular diseases. But the expression pattern and functional roles of GPR30 in vascular smooth muscle cells (VSMCs) remain unclear. In this study, we found that ERalpha, ERbeta, and GPR30 were decreased with VSMCs passaging in vitro or growing in vivo and activation of GPR30 promoted ERalpha expression. Then, we validated that activation of GPR30 significantly decreased migratory capability of VSMCs and suppressed ERalpha, whereas PDGF-BB (20 ng/mL) treatment caused increase of migration. And activation of GPR30 led to reduction of osteopontin and cellular retinol binding protein 1, enhancement of calponin and 3F8, and upregulation of total and phosphorylated ERK1/2 expression in VSMCs knocked down by GPR30, ERalpha, and ERbeta or treated with PDGF-BB. These data suggest that GPR30 promotes VSMCs reducing migration and maintaining differentiated phenotype via activation of ERK1/2 pathway. Our findings provide novel mechanisms of GPR30 protection of VSMCs as well as a new target for prevention of vascular aging. PMID- 27354812 TI - The prognostic roles of ALDH1 isoenzymes in gastric cancer. AB - Increased aldehyde dehydrogenase 1 (ALDH1) activity has been determined to be present in the stem cells of several kinds of cancers including gastric cancer (GC). Nevertheless, which ones of ALDH1's isoenzymes are leading to ALDH1 activity remains elusive. In this study, we examined the prognostic value and hazard ratio (HR) of individual ALDH1 isoenzymes in patients with GC using "The Kaplan-Meier plotter" database. mRNA high expression level of ALDH1A1 was not found to be significantly correlated with the overall survival (OS) of all patients with GC followed for 20 years, HR =0.86 (95% confidence interval [CI]: 0.7-1.05), P=0.13. mRNA high expression level of ALDH1A2 was also not significantly correlated with OS for all patients with GC, HR =1.13 (95% CI: 0.91 1.41), P=0.25. mRNA high expression level of ALDH1A3 was found to be significantly correlated with worsened OS in either intestinal-type patients, HR =2.24 (95% CI: 1.44-3.49), P=0.00026, or diffuse-type patients, HR =1.91 (95% CI: 1.02-3.59), P=0.04. Interestingly, mRNA high expression level of ALDH1B1 was found to be significantly correlated with better OS for all patients with GC, HR =0.66 (95% CI: 0.53-0.81), P=7.8e-05, and mRNA high expression level of ALDH1L1 was found to be significantly correlated with worsened OS for all patients with GC, HR =1.23 (95% CI: 1-1.51), P=0.048. Furthermore, our results also indicate that ALDH1A3 and ALDH1L1 are potential major contributors to the ALDH1 activity in GC, since mRNA high expression levels of ALDH1A3 and ALDH1L1 were found to be significantly correlated with worsened OS for all patients with GC. Based on our study, ALDH1A3 and ALDH1L1 are potential prognostic markers and therapeutic targets for patients with GC. PMID- 27354814 TI - Comparative efficacy and safety of axitinib versus sorafenib in metastatic renal cell carcinoma: a systematic review and meta-analysis. AB - OBJECTIVE: This study was performed to evaluate the comparative efficacy and safety of axitinib and sorafenib in the therapy of metastatic renal cell carcinoma. MATERIALS AND METHODS: Eligible studies were searched from PubMed, Embase, and Future Medicine databases. The pooled hazard ratios and relative risk ratios (RRs) were calculated by using Stata 12.0 software. RESULTS: A total of 1,011 patients qualified to participate in this Phase III study that included randomized controlled trials. Meta-analysis results showed that axitinib was more highly and significantly associated with a survival benefit in the independently assessed progression-free survival in comparison to sorafenib. The values of RR of the objective response rate and disease control rate were also significantly different. Results of the analysis of adverse events concerning hypertension and hypothyroidism demonstrated that the values of RR were significantly higher in the axitinib group and lower risks were established in the patients treated with axitinib. CONCLUSION: Therefore, axitinib was a better treatment option for metastatic renal cell carcinoma treatment than sorafenib, especially after failure of prior systemic therapies. This analysis revealed that axitinib had higher risks of hypertension and hypothyroidism and lower risks of rash and palmar-plantar erythrodysesthesia. PMID- 27354815 TI - Administration of polysaccharide from Panax notoginseng prolonged the survival of H22 tumor-bearing mice. AB - BACKGROUND: Polysaccharides from various sources are being considered potential sources for the treatment of liver cancer. The aim of this study was to investigate the impact of polysaccharide isolated from Panax notoginseng (PPN) on the proliferation of H22 liver cancer cells and the survival of the tumor-bearing mice transplanted with H22 cells. MATERIALS AND METHODS: Polysaccharide from PPN was added to the culture medium of mouse hepatoma H22 cells at different doses. Cell proliferation was assayed with a standard MTT assay. Survival rates of tumor bearing mice were recorded. Peripheral blood lymphocytes were assayed by flow cytometry. Serum interleukin-2 levels in peripheral blood were measured by enzyme linked immunosorbent assay. RESULTS: Polysaccharide from PPN inhibited the growth of H22 cells and significantly prolonged the survival of tumor-bearing mice. The increase in activated CD4(+) T-cells and the elevation of serum interleukin-2 may contribute to the antitumor activity of PPN. CONCLUSION: PPN has potential antitumor activity for the treatment of liver cancer. PMID- 27354816 TI - Comparison of the effectiveness and toxicity of neoadjuvant chemotherapy regimens, capecitabine/epirubicin/cyclophosphamide vs 5 fluorouracil/epirubicin/cyclophosphamide, followed by adjuvant, capecitabine/docetaxel vs docetaxel, in patients with operable breast cancer. AB - The aim of this study was to compare the effectiveness and toxicity of neoadjuvant chemotherapy regimens, xeloda/epirubicin/cyclophosphamide (XEC) vs 5 fluorouracil/epirubicin/cyclophosphamide (FEC), followed by adjuvant chemotherapy regimens, capecitabine/taxotere (XT) vs taxotere (T), in axillary lymph node (LN) positive early-stage breast cancer. In this randomized, Phase III trial, 137 patients with operable primary breast cancer (T2-0, N0-1) who were tested axillary LN positive through aspiration biopsy of axillary LNs were randomized (1:1) to four 3-weekly cycles of XEC or FEC. Patients underwent surgery within 4 6 weeks after the fourth cycle, followed by four adjuvant cycles of 3-weekly XT or T. The primary end point was tumor pathological complete response. Toxicity profiles were secondary objectives. In total, 131 patients had clinical and radiological evaluation of response and underwent surgery. Treatment with XEC led to an increased rate of pathological complete response in primary tumor (18% vs 6%, respectively, P=0.027) and objective remission rate (87% vs 73%, P=0.048) compared to FEC. Clinical complete response occurred in 20% and 7% for XEC and FEC, respectively. Compared to FEC, XEC was associated with more hand-foot syndrome (57% vs 11%, P<0.001) and 3/4 grade nausea/vomiting/diarrhea (30% vs 14%, P=0.034) but less phlebitis (3% vs 14%, P=0.035). XT and T adjuvant chemotherapy regimens were well tolerated: treatment-related 3/4 grade adverse events occurred in 28% and 17% of patients receiving XT and T, respectively. PMID- 27354817 TI - Focus on JNJ-Q2, a novel fluoroquinolone, for the management of community acquired bacterial pneumonia and acute bacterial skin and skin structure infections. AB - JNJ-Q2 is a novel, fifth-generation fluoroquinolone that has excellent in vitro and in vivo activity against a variety of Gram-positive and Gram-negative organisms. In vitro studies indicate that JNJ-Q2 has potent activity against pathogens responsible for acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP), such as Staphylococcus aureus and Streptococcus pneumoniae. JNJ-Q2 also has been shown to have a higher barrier to resistance compared to other agents in the class and it remains highly active against drug-resistant organisms, including methicillin resistant S. aureus, ciprofloxacin-resistant methicillin-resistant S. aureus, and drug-resistant S. pneumoniae. In two Phase II studies, the efficacy of JNJ-Q2 was comparable to linezolid for ABSSSI and moxifloxacin for CABP. Furthermore, JNJ-Q2 was well tolerated, with adverse event rates similar to or less than other fluoroquinolones. With an expanded spectrum of activity and low potential for resistance, JNJ-Q2 shows promise as an effective treatment option for ABSSSI and CABP. Considering its early stage of development, the definitive role of JNJ-Q2 against these infections and its safety profile will be determined in future Phase III studies. PMID- 27354818 TI - Cost-effectiveness of tiotropium versus glycopyrronium in moderate to very severe chronic obstructive pulmonary disease in Canada, Spain, Sweden, and the UK. AB - OBJECTIVES: Tiotropium (TIO), Spiriva(r) Handihaler(r), is a well-established bronchodilator, LAMA (long acting muscarinic antagonist), for the treatment of moderate to very severe chronic obstructive pulmonary disease (COPD). Clinical evidence from the SPARK trial suggests that TIO is superior to glycopyrronium (GLY), Seebri(r) Breezhaler(r), in terms of severe exacerbations. This modeling study assessed the cost-effectiveness of TIO versus GLY for Canada (CAN), Spain (ESP), Sweden (SWE), and the UK, making use of this new clinical evidence. METHODS: A Markov cohort model, with moderate to very severe (Global Initiative for Chronic Obstructive Lung Disease II-IV) COPD patients, was populated with efficacy data from the Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) and SPARK trials as well as costs, utilities, and epidemiological data relevant for each country. Treatment efficacy was modeled as improvements in lung function, quality-adjusted life years (QALYs), and as a lowering of the risk of exacerbations (rate of exacerbations). Risks of exacerbations differed between cohorts based on data from SPARK. Health and cost outcomes were simulated over an approximate lifetime horizon, starting from the age of 65 years. Robustness of results was validated in deterministic sensitivity analyses. RESULTS: Over the lifetime horizon, patients treated with TIO accumulated -623 (CAN), 1,066 (ESP), 1,137 (SWE), and -169 (UK), respectively, in incremental costs (?2014). TIO generated better health outcomes compared to GLY in all countries, 0.21 (CAN), 0.25 (ESP), 0.23 (SWE), and 0.23 (UK) in incremental QALYs. The cost per QALY gained was found to be ?4,281 and ?1,137 for ESP and SWE, respectively, while TIO was found to be cost saving in CAN and the UK. The results were mainly driven by the relative risk of severe exacerbations found in SPARK (GLY/TIO relative risk: 1.43, 95% confidence interval: 1.05-1.97, P=0.025). CONCLUSION: The results from this study show that TIO is a cost effective treatment compared to GLY in moderate to very severe COPD. The cost per QALY is well below the existing implicit and explicit willingness-to-pay thresholds. PMID- 27354819 TI - Novel biomarker analysis of pleural effusion enhances differentiation of tuberculous from malignant pleural effusion. AB - Lymphocytic pleurisy is commonly observed in tuberculosis and cancer. Noninvasive biomarkers are needed to distinguish tuberculous pleural effusion (TPE) from malignant pleural effusion (MPE) because current clinical diagnostic procedures are often invasive. We identified immune response biomarkers that can discriminate between TPE and MPE. Fourteen pleural effusion biomarkers were compared in 22 MPE patients and five TPE patients. Of the innate immunity biomarkers, the median levels of interleukin (IL)-1beta and interferon-induced protein-10 (IP-10) were higher in TPE patients than in MPE patients (P<0.05 and P<0.01, respectively). Of the adaptive immunity biomarkers, the median levels of IL-13 and interferon-gamma (IFN-gamma) were higher in TPE patients than in MPE patients (P<0.05). In addition, the levels of basic fibroblast growth factor were higher in MPE patients than in TPE patients (P<0.05). Receiver operator characteristic analysis of these biomarkers was performed, resulting in the highest area under the curve (AUC) for IP-10 (AUC =0.95, 95% confidence interval, P<0.01), followed by IL-13 (AUC =0.86, 95% confidence interval, P<0.05). Our study shows that five biomarkers (IL-1beta, IP-10, IFN-gamma, IL-13, and basic fibroblast growth factor) have a potential diagnostic role in differentiating TPE from MPE, particularly in lung cancer-related MPE. PMID- 27354820 TI - Atrial fibrillation among the black population in a Ugandan tertiary hospital. AB - BACKGROUND: Atrial fibrillation (AF) is the most common type of sustained cardiac arrhythmia in adults, accounting for one-third of hospitalizations due to arrhythmia and related complications worldwide. Previously, rheumatic heart disease was documented as the commonest cause of AF in sub-Saharan Africa. However, due to the prevailing epidemiological transition in sub-Saharan Africa, the risk factors and ensuing complications of AF have changed and are on the increase. METHODS: This was a descriptive cross-sectional study involving 102 patients presenting with AF who were recruited from the cardiology unit of Mulago National Referral Hospital, Uganda, over 3 months. Sociodemographic, medical history, and clinical data were obtained. RESULTS: The mean age of study participants was 52+/-21.3 years with a female predominance (58 [56.9%]). The commonest coexisting medical conditions were hypertension in 42% and rheumatic heart disease in 32% of the patients. The commonest echocardiographic abnormality was chamber dilation, noted in 76.8% of all patients. Heart failure was the most frequent complication encountered (50%) followed by left ventricular diastolic dysfunction and acute thromboembolic stroke documented in 19.6% and 12.8% of the study participants, respectively. Of the enrolled patients, ten (9.8%) died within 3 days of admission. CONCLUSION: AF tends to occur at a younger age in Ugandan patients. The commonest underlying medical conditions among these patients were hypertension and rheumatic heart disease. Hence, all patients with hypertension and rheumatic heart disease should be meticulously screened for AF. PMID- 27354821 TI - Utilizing a medical questionnaire to predict anxiety and depression in outpatients. AB - INTRODUCTION: Anxiety and depressive symptoms are seen in patients with anxiety and mood disorders but are also common in those with organic disorders. However, since physical symptoms are predominant complaints from patients who visit nonpsychiatric outpatient clinics, anxiety and depressive symptoms are often unrecognized. It is important for physicians to be aware of these issues concurrent with the physical symptoms. We therefore examined whether a self administered medical questionnaire could identify anxiety and depressive symptoms. PATIENTS AND METHODS: A total of 453 patients on their first visit to the Department of General Medicine, Chiba University Hospital, Chiba, Japan, participated in this study. They were asked to complete a medical questionnaire and the Hospital Anxiety and Depression Scale questionnaire before examination. Data on age, sex, number of complaints, symptom duration, and number of previous physicians were extracted from the medical questionnaire. These data were used as independent variables in logistic regression analysis to develop a predictive model for the presence of anxiety and depressive symptoms. RESULTS: Data from 358 (79.0%) patients were included in the analyses. Logistic regression analysis identified the following predictors: "three or more complaints" (odds ratio [OR] 2.39; 95% confidence interval [CI] 1.48-3.88) and "four or more previous physicians" (OR 1.72; 95% CI 1.10-2.69). In the predictive model for the presence of symptoms of anxiety and depression, the likelihood ratio was 2.40 (95% CI 1.33 4.34) in patients reporting both conditions and 1.35 (95% CI 1.04-1.77) in those reporting either condition. CONCLUSION: The presence of anxiety and depressive symptoms can be predicted from the items of a medical questionnaire in outpatients visiting a general medicine department of a university hospital. When patients report three or more complaints or four or more previous physicians on a medical questionnaire, physicians should consider the presence of anxiety or depression or both in differential diagnosis. PMID- 27354822 TI - Erratum: Amino acid management of Parkinson's disease: a case study [Corrigendum]. AB - [This corrects the article on p. 165 in vol. 4, PMID: 21475622.]. PMID- 27354823 TI - Anti-nerve growth factor in pain management: current evidence. AB - There continues to be an unmet need for safe and effective pain medications. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) dominate the clinical landscape despite limited effectiveness and considerable side-effect profiles. Although significant advancements have identified myriad potential pain targets over the past several decades, the majority of new pain pharmacotherapies have failed to come to market. The discovery of nerve growth factor (NGF) and its interaction with tropomyosin receptor kinase A (trkA) have been well characterized as important mediators of pain initiation and maintenance, and pharmacotherapies targeting this pathway have the potential to be considered promising methods in the treatment of a variety of nociceptive and neuropathic pain conditions. Several methodologic approaches, including sequestration of free NGF, prevention of NGF binding and trkA activation, and inhibition of trkA function, have been investigated in the development of new pharmacotherapies. Among these, NGF-sequestering antibodies have exhibited the most promise in clinical trials. However, in 2010, reports of rapid joint destruction leading to joint replacement prompted the US Food and Drug Administration (FDA) to place a hold on all clinical trials involving anti-NGF antibodies. Although the FDA has since lifted this hold and a number of new trials are under way, the long-term efficacy and safety profile of anti-NGF antibodies are yet to be established. PMID- 27354824 TI - Changing prevalence and the risk factors for antenatal obstetric hospitalizations in Denmark 2003-2012. AB - PURPOSE: Population-based studies evaluating the use and extent of antenatal obstetric hospitalizations (AOH) are sparse. The objective of the present study was to describe the prevalence, time trend, and risk factors for AOH in Denmark. MATERIALS AND METHODS: A retrospective national register-based cohort study was conducted that included all pregnancies with delivery after 22 gestational weeks in Denmark from 2003 to 2012. The outcomes were AOH and the diagnoses leading to these hospitalizations. AOH was defined as an antenatal hospitalization for at least 1 day with at least one obstetric International Classification of Diseases 10 diagnosis and admission date more than 3 days before delivery. RESULTS: The study included 617,906 pregnancies; 48,366 (7.8%) pregnancies were associated with 64,072 AOH before delivery. The percentage of pregnancies with AOH decreased from 8.6% to 7.1%. The median length of stay decreased from 3 to 2 days, and admission for at least 7 days was almost halved. Threatened preterm delivery was the most frequent diagnostic category for AOH. A decline was seen in all diagnostic categories except maternal diseases. Significant risk factors for AOH were multiple pregnancies, low or high maternal age and body mass index, nulliparity, lower educational levels, unemployment or being outside the workforce, single partner status, and smoking. The relative risk of very preterm delivery before gestational age of 34 weeks was higher in pregnancies with AOH compared with pregnancies without AOH (relative risk 15.2; 95% confidence interval: 14.6-15.8). CONCLUSION: This study shows a shift toward less use and shorter duration of antenatal hospitalization in Denmark. The most common indication used in pregnancies with AOH was threatened preterm delivery, and more than one-third resulted in very preterm deliveries. PMID- 27354825 TI - Doubling of serum creatinine and the risk of cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes mellitus: a cohort study. AB - BACKGROUND: Doubling of serum creatinine is often used as a marker for worsening kidney function in nephrology trials. Most people with chronic kidney disease die of other causes before reaching end-stage renal disease. We were interested in the association between doubling of serum creatinine and the risk of a first-time diagnosis of angina pectoris, congestive heart failure (CHF), myocardial infarction (MI), stroke, or transient ischemic attack in patients with chronic kidney disease and with diagnosed type 2 diabetes mellitus. METHODS: We identified all adult patients registered in the "Clinical Practice Research Datalink" between 2002 and 2011 with incident chronic kidney disease and type 2 diabetes mellitus and did a cohort study with a Cox proportional hazard analysis. RESULTS: We identified in total 27,811 patients, 693 developed angina pectoris, 1,069 CHF, 508 MI, 970 stroke, and 578 transient ischemic attacks. Patients whose serum creatinine doubled during follow-up had increased risks of CHF (hazard ratio [HR] 2.98, 95% confidence interval [CI] 2.27-3.89), MI (HR 2.53, 95% CI 1.62-3.96), and stroke (HR 1.93, 95% CI 1.38-2.69), as compared with patients whose serum creatinine did not double. The relative risks of angina pectoris (HR 1.18, 95% CI 0.66-2.10) or a transient ischemic attack (HR 1.32, 95% CI 0.78 2.22) were similar in both groups. CONCLUSION: Diabetic patients with a doubling of serum creatinine were at an increased risk of CHF, MI, or stroke, compared with diabetic patients whose serum creatinine did not double during follow-up. PMID- 27354826 TI - Validation of self-reported and hospital-diagnosed atrial fibrillation: the HUNT study. AB - BACKGROUND: Self-reported atrial fibrillation (AF) and diagnoses from hospital registers are often used to identify persons with AF. The objective of this study was to validate self-reported AF and hospital discharge diagnoses of AF among participants in a population-based study. MATERIALS AND METHODS: Among 50,805 persons who participated in the third survey of the HUNT Study (HUNT3), 16,247 participants from three municipalities were included. Individuals who reported cardiovascular disease, renal disease, or hypertension in the main questionnaire received a cardiovascular-specific questionnaire. An affirmative answer to a question on physician-diagnosed AF in this second questionnaire defined self reported AF diagnoses in the study. In addition, AF diagnoses were retrieved from hospital and primary care (PC) registers. All AF diagnoses were verified by review of hospital and PC medical records. RESULTS: A total of 502 HUNT3 participants had a diagnosis of AF verified in hospital or PC records. Of these, 249 reported their AF diagnosis in the HUNT3 questionnaires and 370 had an AF diagnosis in hospital discharge registers before participation in HUNT3. The sensitivity of self-reported AF in HUNT3 was 49.6%, specificity 99.2%, positive predictive value (PPV) 66.2%, and negative predictive value (NPV) 98.4%. The sensitivity of a hospital discharge diagnosis of AF was 73.7%, specificity 99.7%, PPV 88.5%, and NPV 99.2%. CONCLUSION: Use of questionnaires alone to identify cases of AF has low sensitivity. Extraction of diagnoses from health care registers enhances the sensitivity substantially and should be applied when estimates of incidence and prevalence of AF are studied. PMID- 27354827 TI - Challenges in translating endpoints from trials to observational cohort studies in oncology. AB - Clinical trials are considered the gold standard for examining drug efficacy and for approval of new drugs. Medical databases and population surveillance registries are valuable resources for post-approval observational research, which are increasingly used in studies of benefits and risk of new cancer drugs. Here, we address the challenges in translating endpoints from oncology trials to observational studies. Registry-based cohort studies can investigate real-world safety issues - including previously unrecognized concerns - by examining rare endpoints or multiple endpoints at once. In contrast to clinical trials, observational cohort studies typically do not exclude real-world patients from clinical practice, such as old and frail patients with comorbidity. The observational cohort study complements the clinical trial by examining the effectiveness of interventions applied in clinical practice and by providing evidence on long-term clinical outcomes, which are often not feasible to study in a clinical trial. Various endpoints can be included in clinical trials, such as hard endpoints, soft endpoints, surrogate endpoints, and patient-reported endpoints. Each endpoint has it strengths and limitations for use in research studies. Endpoints used in oncology trials are often not applicable in observational cohort studies which are limited by the setting of standard clinical practice and by non-standardized endpoint determination. Observational studies can be more helpful moving research forward if they restrict focus to appropriate and valid endpoints. PMID- 27354828 TI - Implementation of interval walking training in patients with type 2 diabetes in Denmark: rationale, design, and baseline characteristics. AB - Promoting physical activity is a first-line choice of treatment for patients with type 2 diabetes (T2D). However, there is a need for more effective tools and technologies to facilitate structured lifestyle interventions and to ensure a better compliance, sustainability, and health benefits of exercise training in patients with T2D. The InterWalk initiative and its innovative application (app) for smartphones described in this study were developed by the Danish Centre for Strategic Research in T2D aiming at implementing, testing, and validating interval walking in patients with T2D in Denmark. The interval walking training approach consists of repetitive 3-minute cycles of slow and fast walking with simultaneous intensity guiding, based on the exercise capacity of the user. The individual intensity during slow and fast walking is determined by a short initial self-conducted and audio-guided fitness test, which combined with automated audio instructions strives to motivate the individual to adjust the intensity to the predetermined individualized walking intensities. The InterWalk app data are collected prospectively from all users and will be linked to the unique Danish nationwide databases and administrative registries, allowing extensive epidemiological studies of exercise in patients with T2D, such as the level of adherence to InterWalk training and long-term effectiveness surveys of important health outcomes, including cardiovascular morbidity and mortality. Currently, the InterWalk app has been downloaded by >30,000 persons, and the achieved epidemiological data quality is encouraging. Of the 9,466 persons providing personal information, 80% of the men and 62% women were overweight or obese (body mass index >=25). The InterWalk project represents a contemporary technology-driven public health approach to monitor real-life exercise adherence and to propagate improved health through exercise intervention in T2D and in the general population. PMID- 27354829 TI - Topiramate-induced maculopathy in IgG4-related disease. AB - This report describes a case of reversible topiramate-induced maculopathy in a 32 year-old female patient with IgG4-related disease. The patient presented with decreased vision associated with anterior uveitis and cystoid macula edema, which was unresponsive to oral and topical steroids. Following topiramate cessation, both cystoid macula edema and vision improved. The ocular side effects of topiramate and putative pharmacological mechanisms for topiramate-induced maculopathy in the context of IgG4-related disease are discussed. This report highlights that neurologists and ophthalmologists should be aware that patients presenting with topiramate-associated maculopathy should be advised to discontinue topiramate promptly to prevent irreversible loss of vision. PMID- 27354830 TI - Women's autonomy in health care decision-making in developing countries: a synthesis of the literature. AB - Autonomy is considered essential for decision-making in a range of health care situations, from health care seeking and utilization to choosing among treatment options. Evidence suggests that women in developing or low-income countries often have limited autonomy and control over their health decisions. A review of the published empirical literature to identify definitions and methods used to measure women's autonomy in developing countries describe the relationship between women's autonomy and their health care decision-making, and identify sociodemographic factors that influence women's autonomy and decision-making regarding health care was carried out. An integrated literature review using two databases (PubMed and Scopus) was performed. Inclusion criteria were 1) publication in English; 2) original articles; 3) investigations on women's decision-making autonomy for health and health care utilization; and 4) developing country context. Seventeen articles met inclusion criteria, including eleven from South Asia, five from Africa, and one from Central Asia. Most studies used a definition of autonomy that included independence for women to make their own choices and decisions. Study methods differed in that many used study specific measures, while others used a set of standardized questions from their countries' national health surveys. Most studies examined women's autonomy in the context of reproductive health, while neglecting other types of health care utilized by women. Several studies found that factors, including age, education, and income, affect women's health care decision-making autonomy. Gaps in existing literature regarding women's autonomy and health care utilization include gaps in the areas of health care that have been measured, the influence of sex roles and social support, and the use of qualitative studies to provide context and nuance. PMID- 27354831 TI - Case of early-disseminated Rhizopus microsporus var. microsporus mucormycosis in a renal transplant patient. AB - Mucormycosis is a rare infection caused by the ubiquitous filamentous fungi of the order Mucorales and class Zygomycetes. These species are vasotropic, causing rapid onset of tissue infarctions and necrosis and subsequent thrombosis by invading vascular bed. The disease spectrum ranges from involvement of skin, sinuses, lung, and brain to disseminated and mostly fatal infections, especially in immunocompromised hosts. Here, we present a case of a fatal disseminated mucormycosis in a 56-year-old female who had deceased donor renal allograft transplantation ~2 weeks prior to presentation. She presented with shortness of breath and dry cough. Despite being on broad-spectrum antibiotics/antifungals and proper management by transplant, infectious disease, and primary team, she died within 3 weeks of admission. Autopsy showed disseminated mucormycosis of lungs and thyroid. Disseminated infection within 2 weeks of solid organ transplantation in this patient was one of the rare features of mucormycosis. PMID- 27354832 TI - Dilemma in the emergency setting: hypomagnesemia mimicking acute stroke. AB - BACKGROUND: Stroke mimics may account for up to 30% of all acute stroke consultations. However, in the emergency setting, accurate diagnosis is not always possible. METHODS: Case report and review of the literature. RESULTS: A 73 year-old woman was admitted to the emergency department with acute aphasia and right hemiparesis. The National Institute of Health Stroke Score was 21, compatible with severe stroke, so she received thrombolysis. Laboratory testing demonstrated severe hypomagnesemia. She had been taking proton pump inhibitors for years and neuroimaging did not demonstrate signs of acute ischemic disease. After correcting the metabolic alterations with intravenous and oral supplemental magnesium, the patient was discharged asymptomatic. No further episodes have been registered to date. CONCLUSION: Hypomagnesemia might cause acute neurological symptoms that could be confused with stroke. A careful history is essential for diagnosis but suspicion of stroke mimic should not prevent tPA administration. PMID- 27354833 TI - Thyroid surgery with a harmonic scalpel: an experimental study. AB - BACKGROUND: The goal of the study was to determinate the safety of the harmonic scalpel, widely used in thyroidectomy, near the recurrent laryngeal nerve (RLN). METHODS: The study involved ten pigs of either sex. Twenty RLNs at risk were dissected using the new harmonic scalpel FOCUS. The distances between the nerve and the activated instrument were checked with a millimeter ruler. After dissection, the pigs were euthanized, and both RLNs were fixed in formol and examined by histology after staining with hematoxylin-eosin. Due to technical reasons, only 18 RLNs from the ten pigs could be examined. RESULTS: In the experiment that investigated the extent of heat injury, ultrasonic dissection did not cause any immediate damage of the nerve even close to the RLN (1 mm away from the RLN). CONCLUSION: The use of harmonic scalpel FOCUS for thyroid surgery is safe for the surrounding structures (nerves). Careful tissue applications of the device near the RLN (1 mm) did not cause any lesion histologically. PMID- 27354834 TI - Impact of disasters on child stunting in Nepal. AB - BACKGROUND: Stunting is a major public health problem that results from inadequate nutritional intake over a long period of time. Disasters have major implications in poor and vulnerable children. The aim of this study was, therefore, to assess the impact of disasters on child stunting in Nepal. METHOD: A sample consisting of 2,111 children aged 6-59 months was obtained from the 2011 Nepal Demographic and Health Survey. We used bivariate and multivariate analyses to examine moderate and severe stunting against disaster, controlling for all possible confounders. RESULT: Out of the total study sample, 43% were stunted (17.1% severely and 25.9% moderately). The final model, after adjusting for confounders, showed that epidemics have no impact on child stunting (adjusted odds ratio [OR] =1.14, 95% confidence interval [CI]: 0.66, 1.97 and adjusted OR =1.04, 95% CI: 0.66, 1.65 for severe and moderate stunting, respectively). Floods have impact on child stunting (adjusted OR =0.57, 95% CI: 0.31, 0.96 and adjusted OR =0.66, 95% CI: 0.41, 0.94 for severe and moderate stunting, respectively). However, children aged 6-11 months, nonvaccinated children, children of working women, children who live in mountainous areas, and children from the poorest households were more likely to be moderately stunted. Similarly, children aged 36 47 months, Dalit and other ethnic groups, children from rural settings, and children from the poorest households were more likely to be severely stunted. CONCLUSION: This article illustrates the need to rethink about child stunting in Nepal. This study suggests need for further research, integration of disaster data in the Nepal Demography Health Survey, educational interventions, public awareness, promotion of vaccination, and equity in health service delivery. PMID- 27354835 TI - Associations of self-reported and objectively measured sleep disturbances with depression among primary caregivers of children with disabilities. AB - OBJECTIVE: The objective of this study was to determine the association between sleep and depression using both self-reported (subjective) and actigraphic (objective) sleep traits. METHODS: A cross-sectional study was conducted among 175 female primary caregivers of children with disabilities receiving care at a rehabilitation center in Punta Arenas, Chile. The eight-item Patient Health Questionnaire was used to ascertain participants' depression status. The Pittsburgh Sleep Quality Index was used to define subjective, or perceived, sleep quality. Wrist-worn actigraph monitors, worn for seven consecutive nights, were used to characterize objective sleep quality and disturbances. Interviewer administered questionnaires were used to collect information on sociodemographic and lifestyle factors. Linear regression models were fit using continuous sleep parameters as the dependent variables and depression status as the independent variable. Multivariable models were adjusted for body mass index, marital status, smoking status, education level, and children's disabilities. RESULTS: Using an eight-item Patient Health Questionnaire score >=10, 26.3% of participants presented with depression. Depressed women were more likely to self-report overall poorer (subjective) sleep compared to non-depressed women; however, differences in sleep were not consistently noted using actigraphic (objective) sleep traits. Among the depressed, both sleep duration and total time in bed were significantly underestimated. In multivariable models, depression was negatively associated with sleep duration using both subjective (beta=-0.71, standard error [SE] =0.25; P=0.006) and objective sleep (beta=-0.42, SE =0.19; P=0.026). CONCLUSION: The association between sleep and depression differed comparing subjective and objective methods of assessment. Research strategies allowing for the integration of both perceived and objective measures of sleep traits are encouraged. PMID- 27354836 TI - Study on personality dimension negative emotionality affecting academic achievement among Malaysian medical students studying in Malaysia and overseas. AB - Personality dimension negative emotionality is known to be associated with academic achievement. The present study focuses on the influence of negative emotionality (neuroticism) on the medical students' academic achievements. The main objective of this study was to ascertain the negative emotionality scores among the first year Malaysian medical students studying in Malaysia and India, further to find out the association between negative emotionality and their academic achievements. The current study sample includes 60 first year Malaysian medical students from Universiti Sultan Zainal Abidin, Malaysia, and USM-KLE IMP, Belgaum, India. They were selected by convenient sampling technique. The Medico Psychological questionnaire was used to find out the negative emotionality scores among the students and these scores were compared with academic scores. The data were analyzed using SPSS- 20. Thus, the study result goes with the prediction that there is a significant correlation between academic achievement and negative emotionality. We concluded that negative emotionality has a negative impact on medical student's academic achievement regardless of the fact whether they study in their own country or overseas. PMID- 27354837 TI - "Maternal Health and Family Planning Distance Education" experience among physicians: a three-phase study to determine the educational needs, develop education program, and evaluate efficacy of the education administered. AB - AIM: This study aims to assess the educational needs of family practitioners and evaluate the efficacy of the ongoing "Maternal Health and Family Planning Distance Education" program conducted by the General Directorate of Health Research (SAGEM) of the Turkish Ministry of Health. METHODS: This study consisted of three phases. In the first phase, an online survey on maternal health and family planning educational needs was sent to 20,611 physicians via e-mail. Of the 20,611 physicians, 4,729 completed the survey. In the second phase, of the 1,061 physicians registered to the education program, 632 physicians with active participation were included. In the third phase, the preeducation expectations of 287 physicians and posteducation satisfaction of 54 physicians were analyzed with a questionnaire. RESULTS: The majority of the physicians were employed in a family health center (97.4%) and practicing for 16-20 years (23.2%) without any prior in-service training (60.9%). High-to-very high educational need was expressed by 56.4% of physicians for pregnancy, delivery, and puerperality. Topics that the physicians, including both those with >=16 years in practice and without prior in-service training, expressed need for more detailed content were pregnancy, delivery, and puerperality (37.5%); emergency obstetric approach in the primary care setting (33.1%); and gynecological infectious diseases and treatment approach (32.4%). Following the education program, the participants' expectations were fulfilled in terms of refreshing their knowledge, particularly in the field of Maternal Health and Family Planning (87.1% and 75.9%) and the percentage of participants who expressed that they had sufficient high level knowledge increased from 55% to 68.5%. CONCLUSION: The education on Maternal Health and Family Planning refreshed the knowledge of participants and highly met the preeducation expectations. Determining the educational needs and expectations of the target population prior to the education program seems to have an important role on determining its overall success. PMID- 27354838 TI - Tobacco Smoking and the Resting Maternal Brain: A Preliminary Study of Frontal EEG. AB - Tobacco smoking has been attributed to a wide range of detrimental health consequences for both women and their children. In addition to its known physical health effects, smoking may also impact maternal neural responses and subsequent caregiving behavior. To begin investigating this issue, we employed electroencephalography (EEG) to examine resting neural oscillations of tobacco smoking mothers (n = 35) and non-smoking mothers (n = 35). We examined seven EEG frequency bands recorded from frontal electrode sites (delta, theta, alpha, alpha1, alpha2, beta, and gamma). While no between-group differences were present in high-frequency bands (alpha2, beta, gamma), smokers showed greater spectral power in low-frequency bands (delta, theta, alpha, alpha1) compared to non smokers. This increased power in low-frequency bands of tobacco-smoking mothers is consistent with a less aroused state and may be one mechanism through which smoking might affect the maternal brain and caregiving behavior. PMID- 27354839 TI - Associations of Gender, Smoking, and Stress with Transitions in Major Depression Diagnoses. AB - Using data from the newly available U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; Wave 3; n = 36,309), we evaluated relationships among gender, cigarette smoking status (current, former, non-smoker), life event stress (0-1 vs. 2+ events), and their impact on transitions in major depression diagnosis (MDD; new vs. absent cases; ongoing vs. remit cases). Women who were both current and former cigarette smokers with more than two stressful events had higher rates of new MDD diagnosis compared to men who were current or former smokers with two or more stressful events. Current smoking and experiencing two or more stressful events increased the odds of having an ongoing MDD diagnosis, while being a former smoker decreased these odds. Results suggest that smoking and stress are markers for depression risk in women and should help guide clinical assessment as well as gender-difference research on the biological underpinnings of these conditions. PMID- 27354840 TI - Patient Preference for Physician Gender in the Emergency Department. AB - Despite historical gender bias against female physicians, few studies have investigated patients' physician gender preference in the emergency department (ED) setting. We sought to determine if there is an association between ED patient demographics and physician gender preference. We surveyed patients presenting to an ED to determine association between patient demographics and patient physician gender preference for five ED situations: 1) 'routine' visit, 2) emergency visit, 3) 'sensitive' medical visit, 4) minor surgical/'procedural' visit, and 5) 'bad news' delivery. A total of 200 ED patients were surveyed. The majority of ED patients reported no physician gender preference for 'routine' visits (89.5 percent), 'emergent' visits (89 percent), 'sensitive' medical visits (59 percent), 'procedural' visits (89 percent) or when receiving 'bad news' (82 percent). In the setting of 'routine' visits and 'sensitive' medical visits, there was a propensity for same-sex physician preference. PMID- 27354841 TI - Gender-related Differences in Inhibitory Control and Sustained Attention among Adolescents with Prenatal Cocaine Exposure. AB - Adolescence and prenatal cocaine exposure can impact risk-taking. In this study, we evaluated risk-taking and gender-related differences in adolescents with prenatal cocaine exposure in terms of electrophysiological correlates of inhibitory control and sustained attention. No differences related to gender were found within measures of risk-taking, or electrophysiological response relating to risk-taking. Greater responses during inhibition versus attention trials support previous studies, with boys showing the largest responses. Gender-related differences were found when comparing the trials before and after frustration was induced, with greater initial attention indices for girls in both trial types and greater sustained attention for both genders during inhibition trials and for boys during attention trials. These data suggest neural correlates of response inhibition show important gender-related differences in this population. Considering these relationships allows us to further understand underlying processes among adolescents who, as a group, tend to be more inclined toward greater risk behaviors. PMID- 27354842 TI - The Effects of Gender-based Violence on Women's Unwanted Pregnancy and Abortion. AB - The aim of this research is to understand how gender-based violence across the life-course affects the likelihood of abortion. Women outpatients (n = 309) revealed their exposure to four different forms of gender-based abuse: child sexual abuse (25.7 percent), teenage physical dating violence (40.8 percent), intimate partner violence (43.1 percent), and sexual assault outside an intimate relationship (22 percent). Logistic regressions revealed that no single form of gender-based abuse predicted abortion. The cumulative effect of multiple forms of abuse did increase the odds of having an abortion (OR = 1.39, CI = 1.13-1.69). Child sexual abuse predicted intimate partner violence (OR = 6.71, CI = 3.36 13.41). The cumulative effect of gender-based violence on women's reproductive health warrants further research. Priority should be given to screening for multiple forms of victimization in reproductive healthcare settings. PMID- 27354844 TI - Marijuana, the Endocannabinoid System and the Female Reproductive System. AB - Marijuana use among women is highly prevalent, but the societal conversation on marijuana rarely focuses on how marijuana affects female reproduction and endocrinology. This article reviews the current scientific literature regarding marijuana use and hypothalamic-pituitary-ovarian (HPO) axis regulation, ovarian hormone production, the menstrual cycle, and fertility. Evidence suggests that marijuana can reduce female fertility by disrupting hypothalamic release of gonadotropin releasing hormone (GnRH), leading to reduced estrogen and progesterone production and anovulatory menstrual cycles. Tolerance to these effects has been shown in rhesus monkeys, but the effects of chronic marijuana use on human female reproduction are largely unknown. Marijuana-induced analgesia, drug reinforcement properties, tolerance, and dependence are influenced by ovarian hormones, with estrogen generally increasing and progesterone decreasing sensitivity to marijuana. Carefully controlled regulation of the Endocannabinoid System (ECS) is required for successful reproduction, and the exogenous cannabinoids in marijuana may disrupt the delicate balance of the ECS in the female reproductive system. PMID- 27354845 TI - Beyond the Pap Smear: Gender-responsive HIV Care for Women. AB - Women comprise nearly one-quarter of all people living with human immunodeficiency virus (HIV) in the U.S. and 20 percent of incident annual cases. Though women overall are more likely than men to be diagnosed with HIV and engage in care, they are as unlikely to successfully achieve viral suppression with antiretroviral therapy, suggesting gender-based disparities that should be addressed by gender-responsive policies and programs. Using the socioecological model of health and syndemics theory, we comprehensively reviewed published literature to evaluate reasons for and ways to address gender differences in HIV risk and treatment. We discuss the biologic, sociocultural, interpersonal, and behavioral contexts of HIV risk that affect women, comprehensive healthcare for women with HIV that includes pregnancy planning or prevention, and policy implications. PMID- 27354843 TI - Gender-related Differences in Food Craving and Obesity. AB - Food craving is often defined as a strong desire to eat. Much work has shown that it consistently and prospectively predicts eating and weight-related outcomes, contributing to the growing obesity epidemic. Although there are clear gender differences in the prevalence and health consequences of obesity, relatively little recent work has investigated gender differences in craving, or any sex hormone-based differences as they relate to phases of the menstrual cycle. Here, we propose that gender-related differences in food craving contribute to gender related differences in obesity. Drawing on findings in the addiction literature, we highlight ways to incorporate gender-based differences in food craving into treatment approaches, potentially improving the efficacy of obesity and weight loss treatment. Overall, this review aims to emphasize the importance of investigating gender differences in food craving, with a view towards informing the development of more effective treatments for obesity and weight loss. PMID- 27354846 TI - Suicide Prevention Interventions for Sexual & Gender Minority Youth: An Unmet Need. AB - Suicide is currently the second leading cause of death in the U.S. among youth ages 10 to 24. Sexual and gender minority (SGM) youth face heightened risk for suicide and report greater odds of attempting suicide than their heteronormative peers. Contributing factors of experience, which are distinctly different from the experiences of heteronormative youth, place SGM youth at heightened risk for suicide. While interventions aimed at addressing suicide risk factors for all youth are being implemented and many have proven effective in the general population, no evidence-based intervention currently exists to reduce suicide risk within this special population. This perspective article discusses this need and proposes the development of an evidence-based suicide risk reduction intervention tailored to SGM youth. Creating a supportive school climate for SGM youth has been shown to reduce suicide risk and may provide protective effects for all youth while simultaneously meeting the unique needs of SGM youth. PMID- 27354847 TI - Theoretical Approaches to Lentiviral Mediated Neurotrophin Delivery in Potential Treatments of Parkinson's Disease. AB - Parkinson's disease is a late-onset neurodegenerative disease, characterized by both motor and non-motor symptoms. Motor symptoms include postural instability, rigidity, and tremor, while non-motor symptoms include anxiety, dementia, and depression. In this integrative review, we discuss PD disease pathophysiology in detail and introduce how neurotrophic growth factor delivery via a retroviral based system can be used as efficacious tools for targeted gene therapy. PMID- 27354849 TI - A Case for the Demedicalization of Queer Bodies. AB - The medicalization of queer bodies in the clinic and the lab is inexorably linked to the history of LBGTQ politics. Increasingly, activists and scholars are recognizing that while the natural origins of queer sexualities carry a certain political weight, invoking the naturalness of being "born this way" fails to articulate a more substantive challenge to the effects of unexamined cis- and heteronormativity on our social institutions. With this in mind, it is crucial to understand the way these biases operate in scientific research and healthcare so their impact on what we know and how we care can be addressed. It what follows, it will be shown that the medicalization of queer bodies not only fails to diminish these deep-seated biases from sexuality research and clinical practice, but that it also impedes care providers from addressing the healthcare disparities facing queer patients today. PMID- 27354848 TI - Women and Chest Pain: Recognizing the Different Faces of Angina in the Emergency Department. AB - Emergency departments (ED) in the United States see over eight million cases of chest pain annually. While a cardinal symptom of acute coronary syndrome (ACS), multiple emergent and non-emergent causes can attribute to chest pain. This case based perspective describes the different sex-specific causes of angina seen in ED patients. Once coronary artery disease (CAD) is ruled out with standard protocols, microvascular dysfunction is perhaps the most prevalent but under diagnosed cause of non-CAD related angina in ED patients. Additional causes include coronary artery spasm, coronary artery dissection, coronary artery endothelial dysfunction and myocardial bridging. Non-CAD related angina is associated with persistent chest pain causing poor function, quality of life, and recidivism. Clinicians should consider additional diagnostics to routinely screen for non-CAD related causes of angina in patients with recurrent chest pain. Future work is needed to better define the epidemiological, clinical, biological, and genetic correlates of microvascular dysfunction in these patients. PMID- 27354850 TI - Conflations of Marital Status and Sanity: Implicit Heterosexist Bias in Psychiatric Diagnosis in Physician-Dictated Charts at a Midwestern Medical Center. AB - This paper discusses the role of gender role conformity in psychiatric determinants of well-being after of the depathologization of homosexuality from the DSM. In order to examine the heterosexualizing of sanity in U.S. psychiatric and popular cultures, we analyze archived psychiatrist-dictated patient charts from outpatient psychiatric clinics from a Midwestern medical center (n = 45). We highlight ways physicians deployed heteronormative gender expectations to describe and treat women's and men's depressive illness and implicitly construed troubled female-male relationships and sexual encounters as indices of psychopathology. We theorize how evolving connections between the heteronormal and the psychiatric normal performed some of the same regulatory functions, as did the DSM, coding particular gender performances and partner choices as mentally healthy while relegating others to the realm of disease. Only here, focusing on the mainstream instead of the marginalized kept the ideological work of these scripts hidden from view. PMID- 27354851 TI - Balance of the Sexes: Addressing Sex Differences in Preclinical Research. AB - Preclinical research is fundamental for the advancement of biomedical sciences and enhancing healthcare. Considering sex differences in all studies throughout the entire biomedical research pipeline is necessary to adequately inform clinical research and improve health outcomes. However, there is a paucity of information to date on sex differences in preclinical work. As of 2009, most (about 80 percent) rodent studies across 10 fields of biology were still conducted with only male animals. In 2016, the National Institutes of Health implemented a policy aimed to address this concern by requiring the consideration of sex as a biological variable in preclinical research grant applications. This perspective piece aims to (1) provide a brief history of female inclusion in biomedical research, (2) describe the importance of studying sex differences, (3) explain possible reasons for opposition of female inclusion, and (4) present potential additional solutions to reduce sex bias in preclinical research. PMID- 27354852 TI - Perceived Fall Risk and Functional Decline: Gender Differences in Patient's Willingness to Discuss Fall Risk, Fall History, or to Have a Home Safety Evaluation. AB - The CDC reports that among older adults, falls are the leading cause of injury related death and rates of fall-related fractures among older women are twice those of men. We set out to 1) determine patient perceptions (analyzed by gender) about their perceived fall risk compared to their actual risk for functional decline and death and 2) to report their comfort level in discussing their fall history or a home safety plan with their provider. Elders who presented to the Emergency Department (ED?) were surveyed. The survey included demographics, the Falls Efficacy Scale (FES) and the Vulnerable Elders Survey (VES); both validated surveys measuring fall concern and functional decline. Females had higher FES scores (mean 12.3, SD 5.9) than males (mean 9.7, SD 5.9 p = .007) in the 146 surveys analyzed. Females were more likely to report an increased fear of falling, and almost three times more likely to have a VES score of 3 or greater than males (OR = 2.86, 95% CI: 1.17-7.00, p = .02). A strong correlation was observed between FES and VES scores (r = 0.80, p < .001). No difference in correlation was observed between males and females, p = .26. Participants (77 percent) reported they would be comfortable discussing their fall risk with a provider; there was no difference between genders (p = .57). In this study, irrespective of gender, there appears to be a high association between subjects' perceived fall risk and risk for functional decline and death. The majority of patients are likely willing to discuss their fall risk with their provider. These findings may suggest a meaningful opportunity for fall risk mitigation in this setting. PMID- 27354853 TI - Factors relating to the mental health of women who were pregnant at the time of the Great East Japan earthquake: analysis from month 10 to month 48 after the earthquake. AB - BACKGROUND: The Great East Japan Earthquake occurred at 2:46 p.m. on March 11, 2011. The epicenter was off the coast of Miyagi prefecture, and the magnitude of the earthquake was 9.0 with a maximum seismic intensity of 7.0. Although it has already been four years, victims continue to have complex problems. In the stricken areas of Miyagi prefecture, almost ten percent of the residents continue to live in temporary housing. Life altering events that force relocation and a change of living environment are known to adversely affect mental health. The purpose of this study was to examine the mental health of mothers of infants who experienced this disaster in Miyagi prefecture. METHODS: We conducted a survey using The Edinburgh Postnatal Depression Scale (10 months) and The General Health Questionnaire-28, an efficient screening tool for psychiatric distress. Eight hundred eighty-six mothers of children born from February to October, 2011 in Miyagi prefecture were surveyed 10, 16, 24, 36 and 48 months after the disaster. Data were analyzed with the use of SPSS 21.0 J for Windows. The study was approval by the review board of ethics at Tohoku University. RESULTS: The questionnaire was answered by the following number of mothers at the specified months after the disaster: 677 at 10 months, 384 at 16 months, 351 at 24 months, 250 at 36 months and 193 at 48 months. Results at all time periods indicated a high prevalence of psychiatric distress among the mothers surveyed. The percentage of Japanese adults with high-risk GHQ-28 scores is 14 %, thus psychological distress among the subjects in the present study is considerably more widespread. General Health Questionnaire-28 scores were significantly higher for those mothers experiencing dissatisfaction in their marital relationships. We found that mothers have experienced severe mental distress since the disaster, which we think is a possible cause of depression that is leading to poor mental health. CONCLUSION: The results indicate that the upheaval caused by the tsunami affected the mental health of the mothers. Psychological distress continued to be prevalent up to four years after the disaster. Different factors were found to be associated with their distress. The most common issues were economic problems, dissatisfaction in the marital relationship, and no support with childcare. PMID- 27354854 TI - Child mental health in Sierra Leone: a survey and exploratory qualitative study. AB - BACKGROUND: This study complements the growing amount of research on the psychosocial impact of war on children in Sierra Leone by examining local perceptions of child mental health, formal and informal care systems, help seeking behaviour and stigma. METHODS: The study combined: (1) a nationwide survey of mental health care providers, with (2) exploratory qualitative research among service users and providers and other stakeholders concerned with child and adolescent mental health, with a particular emphasis on local explanations and stigma. RESULTS: Formal mental health care services are extremely limited resulting in an estimated treatment gap of over 99.8 %. Local explanations of child mental health problems in Sierra Leone are commonly spiritual or supernatural in nature, and associated with help-seeking from traditional healers or religious institutions. There is a considerable amount of stigma related to mental disorders, which affects children, their caregivers and service providers, and may lead to discrimination and abuse. CONCLUSIONS: Child and Adolescent Mental Health (CAMH) care development in Sierra Leone should cater to the long term structural effects of war-violence and an Ebola epidemic. Priorities for development include: (1) the strengthening of legal structures and the development of relevant policies that strengthen the health system and specifically include children and adolescents, (2) a clearer local distinction between children with psychiatric, neurological, developmental or psychosocial problems and subsequent channelling into appropriate services (3) supplementary CAMH training for a range of professionals working with children across various sectors, (4) specialist training in CAMH, (5) integration of CAMH care into primary health care, education and the social welfare system, (6) further research on local explanations of child mental disorders and the effect they have on the well-being of the child, and (7) a careful consideration of the role of religious healers as care providers. PMID- 27354855 TI - Implementation of a text-messaging intervention for adolescents who self-harm (TeenTEXT): a feasibility study using normalisation process theory. AB - BACKGROUND: There are few interventions that directly address self-harming behaviour among adolescents. At the request of clinicians in Child and Adolescent Mental Health Services (CAMHS) in England and working with them, we redeveloped an adult SMS text-messaging intervention to meet the needs of adolescents under the care of CAMHS who self-harm. METHODS: We used normalisation process theory (NPT) to assess the feasibility of delivering it through CAMHS. We planned to recruit 27 young people who self-harm and their clinicians, working as dyads and using the intervention (TeenTEXT) for 6 months. RESULTS: Despite strong engagement in principle from CAMHS teams, in practice we were able to recruit only three clinician/client dyads. Of these, two dropped out because the clients were too unwell. We identified a number of barriers to implementation. These included: a context of CAMHS in crisis, with heavy workloads and high stress levels; organisational gatekeeping practices, which limited the extent to which clinicians could engage with the intervention; perceived burdensomeness and technophobia on the part of clinicians, and a belief by many clinicians that CAMHS may be the wrong delivery setting and that the intervention may have better fit with schools and universal youth services. CONCLUSIONS: User-centred design principles and the use of participatory methods in intervention development are no guarantee of implementability. Barriers to implementation cannot always be foreseen, and early clinical champions may overestimate the readiness of colleagues to embrace new ideas and technologies. NPT studies have an important role to play in identifying whether or not interventions are likely to receive widespread clinical support. This study of a text-messaging intervention to support adolescents who self-harm (TeenTEXT) showed that further work is needed to identify the right delivery setting, before testing the efficacy of the intervention. PMID- 27354856 TI - Erratum to: Engineering Escherichia coli for high-yield geraniol production with biotransformation of geranyl acetate to geraniol under fed-batch culture. AB - [This corrects the article DOI: 10.1186/s13068-016-0466-5.]. PMID- 27354857 TI - Genome wide analysis of protein production load in Trichoderma reesei. AB - BACKGROUND: The filamentous fungus Trichoderma reesei (teleomorph Hypocrea jecorina) is a widely used industrial host organism for protein production. In industrial cultivations, it can produce over 100 g/l of extracellular protein, mostly constituting of cellulases and hemicellulases. In order to improve protein production of T. reesei the transcriptional regulation of cellulases and secretory pathway factors have been extensively studied. However, the metabolism of T. reesei under protein production conditions has not received much attention. RESULTS: To understand the physiology and metabolism of T. reesei under protein production conditions we carried out a well-controlled bioreactor experiment with extensive analysis. We used minimal media to make the data amenable for modelling and three strain pairs to cover different protein production levels. With RNA sequencing transcriptomics we detected the concentration of the carbon source as the most important determinant of the transcriptome. As the major transcriptional response concomitant to protein production we detected the induction of selected genes that were putatively regulated by xyr1 and were related to protein transport, amino acid metabolism and transcriptional regulation. We found novel metabolic responses such as production of glycerol and a cellotriose-like compound. We then used this cultivation data for flux balance analysis of T. reesei metabolism and demonstrate for the first time the use of genome wide stoichiometric metabolic modelling for T. reesei. We show that our model can predict protein production rate and provides novel insight into the metabolism of protein production. We also provide this unprecedented cultivation and transcriptomics data set for future modelling efforts. CONCLUSIONS: The use of stoichiometric modelling can open a novel path for the improvement of protein production in T. reesei. Based on this we propose sulphur assimilation as a major limiting factor of protein production. As an organism with exceptional protein production capabilities modelling of T. reesei can provide novel insight also to other less productive organisms. PMID- 27354858 TI - Novel microduplication of CHL1 gene in a patient with autism spectrum disorder: a case report and a brief literature review. AB - BACKGROUND: The cell adhesion molecule L1-like (CHL1 or CALL) gene is located on chromosome 3p26.3, and it is highly expressed in the central and peripheral nervous systems. The protein encoded by this gene is a member of the L1 family of neural cell adhesion molecules, and it plays a role in nervous system development and synaptic plasticity. Moreover, studies of mice have revealed that CHL1 is a prime candidate gene for a dosage-sensitive autosomal form of mental retardation. To date, four patients with a microdeletion and two with a microduplication of 3p26.3 encompassing only the CHL1 gene have been reported in literature. CASE PRESENTATION: In the present study, we have described a 16-month-old boy with autism spectrum disorder (ASD), developmental delay and minor dysmorphic facial features. This is the first report of a duplication of 3p26.3 including only the CHL1 gene in an ASD patient, and this duplication is the smallest reported to date in this gene. We also reviewed CHL1 gene mutation cases and examined whether this gene has an important role in cognitive function. CONCLUSIONS: We conclude that both CHL1 deletions and duplications are likely responsible for the patient's impaired cognitive function, and CHL1 may be an intriguing ASD candidate gene. PMID- 27354859 TI - Management of antithrombotic therapy during cardiac implantable device surgery. AB - Anticoagulants are commonly used drugs that are frequently encountered during device placement. Deciding when to halt or continue the use of anticoagulants is a balance between the risks of thromboembolism versus bleeding. Patients taking warfarin with a high risk of thromboembolism should continue to take their warfarin without interruption during device placement while ensuring their international normalized ratio remains below 3. For patients who are taking warfarin and have low risk of thromboembolism, either interrupted or continued warfarin may be used, with no evidence to clearly support either strategy. There is little evidence to support continuing direct acting oral anticoagulants (DOACs) for device implantation. The timing of halting these medications depends largely on renal function. If bleeding occurs, warfarin's anticoagulation effect is reversible with vitamin K and activated prothrombin complex concentrate. There are no DOAC reversal agents currently available, but some are under development. Regarding antiplatelet agents, aspirin alone can be safely continued while clopidogrel alone may also be continued, but with a slightly higher bleeding risk. Dual antiplatelet therapy for bare-metal stent/drug-eluting stent implanted within 4 weeks/6 months, respectively, should be continued due to high risk of stent thrombosis; however, if they are implanted after this period, then clopidogrel can be halted 5 days before the procedure and resumed soon after, while aspirin is continued. If the patient is taking both aspirin and warfarin, aspirin should be halted 5 days prior to the procedure, while warfarin is continued. PMID- 27354860 TI - Impact of transesophageal echocardiography during transseptal puncture on atrial fibrillation ablation. AB - BACKGROUND: The aim of our study was to demonstrate the added value of routine transesophageal echocardiography (TEE) for correctly positioning the transseptal system in the fossa ovalis (FO), thus potentially preventing complications during fluoroscopy-guided transseptal puncture (TP), and for assessing the optimal puncture site within the FO according to the expected procedure type. METHODS: Ninety-one patients undergoing pulmonary vein isolation (PVI) procedures by cryoballoon technique for drug-resistant paroxysmal or persistent atrial fibrillation (AF) were prospectively included. In 57 patients, the TP procedure was performed under fluoroscopic guidance and septal localization was confirmed by contrast injection through the needle and demonstration of septal tenting in both the anteroposterior and left lateral fluoroscopic projections. In 34 patients, TP was performed under TEE guidance and positioning was targeted to perform the TP procedure in the more anterior and inferior locations of the FO. Two patient groups were compared according to the incidence of complications directly attributable to transseptal catheterization, thromboembolic complications, recurrence rates after the ablation procedure, total procedural time, and fluoroscopy time. RESULTS: Fluoroscopy time (p<0.001), total cryoablation time (p=0.002), and total procedural time (p<0.001) were shorter in the TEE-guided group. Left inferior pulmonary vein (LIPV) cryoablation time (p=0.007) and right inferior pulmonary vein (RIPV) cryoablation time (p=0.004) were significantly shorter and the number of applications to the LIPV (p=0.007) and RIPV (p=0.005) were significantly fewer in the TEE-guided group. Although there was a trend toward higher complication rates (20.6% vs. 31.6%, p=0.37) and recurrence rates (11.8% vs. 20.1%, p=0.26) in the fluoroscopy-guided group, the differences between the groups were not statistically significant. CONCLUSIONS: TEE-guided TP for AF ablation is associated with shorter fluoroscopy time, shorter total cryoablation time, and shorter total procedural time. Importantly, TEE-guided TP facilitates cryoablation of the inferior pulmonary veins. PMID- 27354861 TI - Radiofrequency catheter ablation of left-sided accessory pathways via retrograde aortic approach in children. AB - BACKGROUND: We aimed to analyze the results of retrograde aortic radiofrequency catheter ablation of left-sided accessory pathways in children. METHODS: Between January 2010 and September 2014, 25 children who underwent left-sided accessory pathway ablation with a retrograde aortic approach were evaluated retrospectively. RESULTS: The mean age of the patients was 11.09+/-3.71 years. Seventeen patients were male (68%). The mean procedure and fluoroscopy times were 71.54+/-21.05 min and 31.42+/-19.57 min, respectively. Radiofrequency energy was delivered with 41.38+/-15.32 W at 52.38+/-5.45 degrees C. Sixteen patients (64%) presented with manifest preexcitation and, 9 had concealed accessory pathways. The location of accessory pathway was left lateral in 16 patients, posteroseptal in 5, left anterolateral in 2, and left posterolateral and left posterior in the remaining 2. The acute success rate was 96%. The patients were followed for a mean of 16.68+/-18.01 months. There were 2 recurrences. No major complications were observed in the periprocedural period. One patient had groin hematoma, another one had transient severe headache and vomiting. Trivial mitral regurgitation was noted in a patient, which remained the same throughout follow up. None of the patients developed new aortic regurgitation, pericardial effusion, or thrombi at the site of ablation. CONCLUSIONS: The retrograde aortic approach can be safely employed with a high success rate for ablation of left sided accessory pathways in children. PMID- 27354862 TI - Clinical and electrocardiographic predictors of T wave oversensing in patients with subcutaneous ICD. AB - BACKGROUND: T wave oversensing (TWOS) is a major drawback of the subcutaneous implantable cardioverter defibrillator (S-ICD). Data on predictors of TWOS in S ICD recipients are limited. We sought to investigate predictors of TWOS in a cohort of patients receiving an S-ICD at our institution. METHODS: S-ICD recipients at our center were identified retrospectively and stratified based on the presence or absence of TWOS. Clinical and electrocardiographic parameters were collected and compared between the 2 groups. RESULTS: Ninety-two patients underwent an S-ICD implantation at our institution between April 2010 and January 2015. Six (6.5%) patients had TWOS. These patients were younger (38.1+/-13.7 vs. 52.3+/-16.1 years, p=0.04) and had higher left ventricle ejection fractions (48.5+/-14.9% vs. 28.4+/-12.2%, p<0.01) than patients without a history of TWOS. Baseline 12-lead electrocardiogram (ECG) parameters were not different between the 2 groups. Leads I, II, and avF (which mimic the sensing vectors of the S-ICD) were further inspected to identify ECG characteristics that could predict TWOS. The QRS amplitude in ECG lead I was significantly smaller in the TWOS group than in the non-TWOS group (3.7 vs. 7.4 mV, p=0.02). CONCLUSION: In this study, younger age, higher ejection fraction, and lower QRS amplitude were associated with TWOS. These findings could help identify patients referred for S-ICD at high risk of TWOS. PMID- 27354863 TI - A multicenter observational study of the effectiveness of antiarrhythmic agents in ventricular arrhythmias: A propensity-score adjusted analysis. AB - BACKGROUND: Ventricular tachyarrhythmias (VTs) are life-threatening events that result in hemodynamic compromise. Recurrence is common and may worsen a patient's clinical course despite appropriate treatment. This study aimed to examine the effectiveness of antiarrhythmic drugs for suppression of VTs. METHODS: In this cohort study, eligible patients were those who were admitted to one of the nine cardiovascular care centers and treated with continuous infusion of an antiarrhythmic drug for at least 1 h to prevent recurrence of VTs after return of spontaneous circulation. To adjust for differences in baseline characteristics among treatment groups, propensity scores for administered agents were generated and used as covariates in regression analyses. RESULTS: Seventy-two patients were enrolled and 67 patients were included in the final analysis. Amiodarone (n=21, 31.3%), nifekalant (n=24, 35.8%), and lidocaine (n=22, 32.8%) were administered as first-line therapy for suppression of VTs. In the adjusted analyses, the odds ratio (OR) of switching to a different drug was significantly higher in the lidocaine group (OR 37.6, 95% CI 5.1-279, p<0.001) than in the amiodarone group, but not in the nifekalant group (OR 4.1, 95% CI 0.72-23.2, p=0.11). There was no significant difference in mortality rate in the lidocaine group (OR 1.67, 95% CI 0.40-6.95, p=0.48) or the nifekalant group (OR 1.11, 95% CI 0.15-4.85, p=0.89) compared with the amiodarone group. CONCLUSION: Amiodarone and nifekalant are similarly effective in preventing VT recurrence, but their impact on survival rate is minimal. These data indicate that both nifekalant and amiodarone can be used for treatment of refractory VT. PMID- 27354864 TI - Efficacy of atorvastatin in prevention of atrial fibrillation after heart valve surgery in the PROFACE trial (PROphylaxis of postoperative atrial Fibrillation After Cardiac surgEry). AB - BACKGROUND: To evaluate the efficacy of perioperative atorvastatin administration for prophylaxis of postoperative atrial fibrillation (POAF) after heart valve surgery. METHODS: Our study included 90 patients with heart valve disease who were scheduled to undergo elective cardiac surgery. Cases with previous AF or preoperative beta-blocker therapy were excluded. Patients were randomized into the atorvastatin group, which included 47 patients who received 40 mg/day of atorvastatin 7 days before and after the surgery and the control group, which included 43 patients. Primary endpoint was the occurrence of POAF. Secondary endpoints included modifications in the preoperative and postoperative levels of the markers of inflammation (C-reactive protein [CRP]), myocardial injury (ultrasensitive troponin T and creatinine phosphokinase MB [CPK-MB]), and cardiac dysfunction (pro-brain natriuretic peptide [proBNP]) related to POAF and changes in the echocardiographic parameters, such as atrial electromechanical interval, A wave, E/A ratio, and Doppler imaging systolic velocity wave amplitude, related to POAF. RESULTS: No relationship between atorvastatin administration and reduction in the incidence of POAF was observed (42.6% in the atorvastatin vs. 30.2% in the control group) (p=0.226). No difference in the levels of CPK-MB, ultrasensitive troponin T, CRP, or proBNP and in the analyzed echocardiographic parameter was detected between both groups. CONCLUSIONS: Atorvastatin in the described dose, was not adequate for the prophylaxis of POAF after heart valve surgery. It was ineffective in controlling the inflammatory phenomena, myocardial injury, and echocardiographic predictors of POAF. PMID- 27354865 TI - The feasibility of a Box isolation strategy for non-paroxysmal atrial fibrillation in elderly patients. AB - BACKGROUND: Catheter ablation of non-paroxysmal atrial fibrillation (non-PAF) is a therapeutic challenge especially in elderly patients. This study describes the feasibility of a posterior left atrium isolation as a substrate modification in addition to pulmonary vein isolation, the so-called Box isolation, for elderly patients with non-PAF. METHODS: Two hundred twenty-nine consecutive patients who underwent Box isolations for drug-refractory non-PAF were divided into two groups according to their age; younger group comprising 175 patients aged <75 years and elderly group comprising 54 patients aged >=75 years. RESULTS: During 23.7+/-12.0 months of follow-up, the arrhythmia-free rates after one procedure were 53.1% in younger group versus 48.1% in elderly group (p=0.50). Following the second procedure, all patients had electrical conduction recoveries along the initial Box lesion. However, a complete Box re-isolation was highly established in both age groups (87.1% vs. 92.9%, respectively; p=1.00). Recurrence of macro-reentrant atrial tachycardia was mainly associated with the gaps through the initial Box lesion in both age groups (25.8% vs. 21.4%, p=1.00), but typical cavo-tricuspid isthmus (CTI) dependent atrial flutter was significantly observed in the elderly patients' group only (all events were observed within 6 months after the initial procedure; 3.2% vs. 28.6%, p=0.009). After two procedures, the arrhythmia-free rates increased to 73.1% in younger group versus 66.7% in elderly group (p=0.38). The occurrence rate of procedural-related complications did not differ between the two age groups, and there were no life-threatening complications even in elderly patients. CONCLUSIONS: Box isolation of non-PAF is effective and safe even in elderly patients. A prophylactic CTI ablation combined with Box isolation might be feasible to improve the long-term outcome. PMID- 27354866 TI - Anti-arrhythmic medications increase non-cardiac mortality - A meta-analysis of randomized control trials. AB - INTRODUCTION: Anti-arrhythmic medications (AAMs) are known to increase cardiac mortality significantly due to their pro-arrhythmic effects. However, the effect of AAMs on non-cardiac mortality has not been evaluated. METHODS: Trials published in English language journals from 1990 to 2015 were thoroughly retrieved by searching websites such as PubMed, Medline, Cochrane Library, and Google Scholar. Randomized controlled trials reporting non-cardiac deaths as primary or secondary outcomes were used to compare AAMs to non-arrhythmic therapy (AV nodal blocking agents, implantable cardiovascular defibrillation (ICD), or placebo). Information regarding the sample size, treatment type, baseline characteristics, and outcomes was obtained by using a standardized protocol. The fixed effect model was used to perform meta-analysis, and results were expressed in terms of odds ratio (OR) with confidence interval (CI) of 95%, inter study heterogeneity was assessed using I (2). Intention to treat principle was applied to extract data. RESULTS: Total of 18,728 patients were enrolled in 15 trials; 9359 patients received AAMs and 9369 received non-arrhythmic therapy. AAMs were associated with an increased risk of non-cardiac mortality (OR=1.30, [95% CI: 1.12, 1.50], p=0.0005, I (2) index=24%) and all-cause mortality (OR=1.09, [95% CI: 1.01, 1.18], p=0.04, I (2)=54%) as compared to non-arrhythmic therapy. There was no difference in the cardiac mortality (OR=1.01, [95% CI: 0.92, 1.11], p=0.82, I (2)=53%) or arrhythmic mortality (OR=1.00, [95% CI: 0.89, 1.13], p=0.94, I (2)=64%) between the two groups. CONCLUSION: AAMs are associated with an increased risk of non-cardiac and all-cause mortality. The effect of AAMs, especially amiodarone, on non-cardiac mortality requires further evaluation. PMID- 27354867 TI - Efficacy of atrial substrate modification based on dominant frequency of paroxysmal atrial fibrillation. AB - BACKGROUND: The endpoint of ablation procedures is suggested to be non inducibility of paroxysmal atrial fibrillation (PAF). However, the prognosis of induced AF/atrial tachycardia (AT) after pulmonary vein isolation (PVI) in PAF patients remains unclear. METHODS: A total of 122 PAF patients were divided into the following 3 groups: Group 1, 79 without AF/AT induced after PVI; Group 2, 21 with AF/AT induced or sustained after PVI, and followed by a high-dominant frequency (DF) and continuous complex fractionated atrial electrogram (CFAE) site ablation and, if necessary, linear ablation; and Group 3, 22 with external cardioversion of AF/AT induced or sustained after PVI. High-DF (DF>=8 Hz) and continuous CFAE (fractionated intervals<=50 ms) sites were targeted. The ablation endpoint was non-inducibility of PAF. RESULTS: In Group 2, AF terminated in 2 patients with a high-DF and continuous CFAE site ablation. In 4 patients, AF induced after cardioversion did not terminate with left atrium linear ablation, and required additional cardioversion. Common atrial flutter in 2 patients terminated with cavotricuspid isthmus ablation. An AT terminated with a roofline ablation. Finally, no AF/AT could be induced in any of the patients in Group 2 after all the procedures. The cumulative freedom from AF/AT recurrence without antiarrhythmic drugs in Groups 1 and 2 was significantly greater than that in Group 3 after 1 procedure during 12 months of follow-up (90% and 91% vs. 64%, Log rank test P=0.001 and P=0.033, respectively). CONCLUSIONS: Atrial substrate ablation may improve the clinical outcome after ablation in patients after PVI with residual arrhythmia inducibility. PMID- 27354868 TI - Home monitoring report from a single lead Lumax DX implantable cardioverter defibrillator: New observations in a new system. AB - A 56-year-old man underwent a single lead Lumax 640 DX implantable cardioverter defibrillator implantation for primary prevention of sudden cardiac death. A DX system consists of a single lead, which provides atrial as well as ventricular electrograms, and enhances atrial arrhythmia detection. Three months after the implantation, high-frequency episodes were detected on the far field and the atrial channels, but not on the bipolar right ventricular channel; these were classified as atrial tachycardia. In the present report, we discussed the unusual pattern of the artifacts that was related to an electromagnetic interference detected by the novel DX system. PMID- 27354869 TI - Alternative approach for management of an electrical storm in Brugada syndrome:Importance of primary ablation within a narrow time window. AB - Placement of an implantable cardioverter-defibrillator (ICD) is the only powerful treatment modality for Brugada syndrome in patients presenting with ventricular fibrillation (VF). For those whose first presentation is an electrical storm, pharmacologic therapy is typically used to control VF followed by ICD implantation. We report an alternative approach whereby, before ICD implantation, emergency catheter ablation of the VF-triggering premature ventricular contraction (PVC) resulted in long-term VF-free survival. The results suggest that, because VF triggers appear in a narrow time window, ablation of the culprit PVCs that initiate VF before the index PVCs subside is a reasonable alternative approach. PMID- 27354870 TI - Intermuscular pocket for subcutaneous implantable cardioverter defibrillator: Single-center experience. AB - The subcutaneous implantable cardioverter defibrillator (S-ICD) is a novel device now accepted in clinical practice for treating ventricular arrhythmias. In 14 consecutive patients, S-ICD devices were placed in the virtual space between the anterior surface of the serratus anterior muscle and the posterior surface of the latissimus dorsi muscle. During a mean follow up of 9 months, no dislocations, infections, hematoma formations, or skin erosions were observed. Intermuscular implantation of the S-ICD could be a reliable, safe, and appealing alternative to the standard subcutaneous placement. PMID- 27354871 TI - Histological examination of the right atrial appendage after failed catheter ablation for focal atrial tachycardia complicated by cardiogenic shock in a post partum patient. AB - A 26-year-old woman in her first pregnancy presented with persistent atrial tachycardia (AT). AT was resistant to medications, cardioversions, and the first attempt of catheter ablation. Two months after delivery she developed severe systolic dysfunction and circulatory collapse. Emergent catheter ablation was performed with the support of percutaneous cardiopulmonary bypass and intraaortic balloon pump. The AT originated in the apex of the right atrial appendage (RAA). Repeated attempts at ablation were unsuccessful, prompting surgical RAA resection, which terminated the tachycardia and improved the cardiac function. Histological examination of resected RAA provided insights into mechanism of resistance to catheter ablation. PMID- 27354872 TI - Eccentric scar formation around a pulmonary vein after cryo-balloon ablation in a patient with atrial fibrillation: A case report. AB - The impact of a cryoballoon ablation is reported to be similar to that of a radiofrequency (RF) ablation in patients with atrial fibrillation. Delayed enhancement magnetic resonance imaging (DE-MRI) could visualize the scar region induced by the cryoballoon ablation as well as RF ablation. Cryoballoon ablation could induce extensive scar lesions around the PVs. However, the distribution of the scar lesions after the cryoballoon ablation has not been well discussed. We, herein, described a case with an eccentric scar distribution after cryoballoon ablation. PMID- 27354873 TI - Resolution of a warfarin and dabigatran-resistant left atrial appendage thrombus with apixaban. AB - The majority of embolisms associated with atrial fibrillation (AF) are from the left atrial appendage (LAA). To treat the existing thrombus, warfarin and novel anticoagulants have been used. However, there has been no clinical information regarding the difference of the effects of congealing the fibrinogenolysis system among these oral anticoagulants. Here, we report a case of persistent AF, in whom apixaban, factor Xa inhibitor resolved an LAA clot refractory to warfarin and direct thrombin inhibition. Factor Xa inhibitor, apixaban, could resolve the left appendage thrombosis refractory to warfarin and dabigatran. PMID- 27354874 TI - Double twiddle trouble, a new variant of twiddler syndrome. AB - The twiddler syndrome results in retraction and coiling of the lead in the pacemaker pocket with subsequent pacemaker malfunction. If the lead's parameters are not affected, then the problem can be corrected by lead repositioning. We describe the first reported case of a dramatic pacemaker lead coiling with a double level of lead compromise, with one of them being intra-cardiac. This condition affected our treatment strategy, as the repositioning of the lead was unfeasible. PMID- 27354875 TI - Letter to the Editor: Marino et al. Inappropriate mode switching clarified by using a chest radiograph. PMID- 27354876 TI - ST elevation without cardio-pulmonary symptoms. PMID- 27354877 TI - Successful dual chamber ICD implantation via a persistent left superior vena cava after ratchet syndrome. PMID- 27354878 TI - Hemolytic Uremic Syndrome Causing Multicystic Leukoencephalomalacia. AB - BACKGRUND: Hemolytic uremic syndrome is a disease characterized by hemolytic anemia, thrombocytopenia and acute renal failure with multiple organ involvement. Central nervous system involvement is detected in 20-50% of the patients and this leads to increased morbidity and mortality. CASE REPORT: We report the neuroimaging findings in a four-month-old male with hemolytic uremic syndrome. The cerebral cortex and white matter showed mild signal intensity on T2-weighted images. The diffusion weighted imaging demonstrated restricted diffusion in the cerebral cortex and white matter with corresponding low signal intensity on the apparent diffusion coefficient maps representing cytotoxic edema. These findings ended in multicystic leukoencephalomalacia. CONCLUSIONS: In hemolytic uremic syndrome with brain involvement symptoms develop due to the different level of actions of factors and thus MRI protocol towards cerebral parenchyma should include DWI, especially in pediatric patients. PMID- 27354879 TI - An Extremely Rare Coexistence: Acute Appendicitis and Multiple Intussusceptions in an Adult. AB - BACKGROUND: Adult intussusception is a rare phenomenon, acute appendicitis accompanying multiple transient intussusceptions are much more uncommon. Satisfaction and quiting imaging studies after finding an intussusception on ultrasound, may lead diagnostic errors. Radiologists should raise their awareness of imaging findings in intussusception and keep in their mind coexistent troubles in the belly. This unique case presents unusual imaging findings of a rare dual abdominal emergency condition, particularly highlighting the value of abdominal computed tomography. CASE REPORT: 32-year-old female was admitted to Emergency Department with complaints of epigastric abdominal pain and vomiting. US identified 'target' appereance on left paramedian location at umbilical level. Contrast enhanced abdominal CT not only confirmed the enteric intussusception that was demonstrated on previos US, but also showed additional concomitant intussusceptions and inflamed appendix. CONCLUSIONS: Adult intussusception is a rare phenomenon, multiple transient intussusceptions are even more uncommon. This unique report adds, precious clinical and imaging findings of acute appendicitis coexisting with multiple spontaneously resolving intussusceptions, to the literature. Physicians should be alerted for accompanying multiple abdominal pathologies and use justification essentials to make their decisions about the selection of the appropriate imaging modality. PMID- 27354880 TI - Jugular Vein Invasion Diagnosis and Prognosis in Thyroid Carcinomas. AB - Diagnosis of venous jugular invasion by means of traditional imaging is very rarely reported in the literature. Doppler ultrasound definitively helps to diagnose the tumor thrombus, the extent, and helps in redefining the TNM stage of such an aggressive thyroid tumor. PMID- 27354881 TI - A Comparison of Cobb Angle: Standing Versus Supine Images of Late-Onset Idiopathic Scoliosis. AB - BACKGROUND: Scoliosis is traditionally evaluated by measuring the Cobb angle in radiograph images taken while the patient is standing. However, low-dose computed tomography (CT) images, which are taken while the patient is in a supine position, provide new opportunities to evaluate scoliosis. Few studies have investigated how the patient's position, standing or supine, affects measurements. The purpose of this study was to compare the Cobb angle in images from patients while standing versus supine. MATERIAL/METHODS: A total of 128 consecutive patients (97 females and 21 males; mean age 15.5 [11-26] years) with late-onset scoliosis requiring corrective surgery were enrolled. One observer evaluated the type of curve (Lenke classification) and measured the Cobb angle in whole-spine radiography (standing) and scout images from low-dose CT (supine) were taken on the same day. RESULTS: For all primary curves, the mean Cobb angle was 59 degrees (SD 12 degrees ) while standing and 48 degrees (SD 12 degrees ) while in the supine position, with a mean difference of 11 degrees (SD 5 degrees ). The correlation between primary standing and supine images had an r value of 0.899 (95% CI 0.860-0.928) and an intra-class correlation coefficient value of 0.969. The correlation between the difference in standing and supine images from primary and secondary curves had an r value of 0.340 (95% CI 0.177-0.484). CONCLUSIONS: We found a strong correlation between the Cobb angle in images obtained while the patient was standing versus supine for primary and secondary curves. This study is only applicable for patients with severe curves requiring surgical treatment. It enables additional studies based on low-dose CT. PMID- 27354882 TI - Eagle Syndrome Causing Vascular Compression with Cervical Rotation: Case Report. AB - BACKGROUND: Eagle syndrome is a condition caused by an elongated styloid process. Unilateral face, neck and ear pain, stinging pain, foreign body sensation and dysphagia can be observed with this syndrome. Rarely, the elongated styloid process may cause pain by compressing the cervical segment of the internal carotid and the surrounding sympathetic plexus, and that pain spreading along the artery can cause neurological symptoms such as vertigo and syncope. CASE REPORT: In this case report we presented a very rare eagle syndrome with neurological symptoms that occurred suddenly with cervical rotation. The symptoms disappeared as suddenly as they occurred, with the release of pressure in neutral position. We also discussed CT angiographic findings of this case. CONCLUSIONS: Radiological diagnosis of the Eagle syndrome that is manifested with a wide variety of symptoms and causes diagnostic difficulties when it is not considered in the differential diagnosis is easy in patients with specific findings. CT angiography is a fast and effective examination in terms of showing compression in patients with the Eagle syndrome that is considered to be atypical and causes vascular compression. PMID- 27354883 TI - The Role of Computerized Tomography in the Assessment of Perivesical Invasion in Bladder Cancer. AB - BACKGROUND: The aim of the present study was to identify the contrast patterns of a tumor, and to evaluate the possibility of assessing the invasion of the perivesical fatty tissue in bladder cancer. MATERIAL/METHODS: In this study, 26 patients with bladder cancer were included. Multiphasic CT examination was performed to determine the stage of the disease before radical cystectomy. RESULTS: There were statistically significant differences in tumor and perivesical fatty tissue densities between pre- and post-contrast phases (p<0.05). CONCLUSIONS: Increases in focal density suspected of being invasion of the perivesical fatty tissue can show perivesical invasion with high specificity. PMID- 27354884 TI - Tolerability of Ingenol Mebutate Gel, 0.05%, for Treating Patients with Actinic Keratosis on the Scalp in a Community Dermatology Practice. AB - OBJECTIVE: To describe the safety, tolerability, and efficacy of treatment of actinic keratosis on the scalp with two consecutive, once-daily applications of ingenol mebutate gel, 0.05%. DESIGN: Retrospective chart review. SETTING: Community dermatology practice. PARTICIPANTS: Male patients (N=78) with a long history of recurrent and relapsed scalp actinic keratosis. MEASUREMENTS: This chart review extracted non-identifying information on patients' medical history, pertinent history of actinic keratosis and skin cancer, and prior actinic keratosis treatments. Also collected was information on patients' treatment of scalp actinic keratosis with ingenol mebutate gel, 0.05%, including the occurrence of local skin reactions and their treatment, adverse events, and efficacy results at short-term and additional follow-up. RESULTS: In these patients, a significant proportion of the scalp had numerous actinic keratoses that were often recurrent and/or hyperkeratotic. Most patients (83%) received cryosurgery to visible scalp actinic keratoses two weeks before ingenol mebutate treatment. Local skin reactions developed on the first day of topical treatment, were predominantly mild or moderate in intensity, and generally were resolved by 10 to 14 days. Local skin reactions were treated with a topical moisturizing product in 44 percent of the patients. Nearly half (45%) of the patients experienced application-site reactions, described as a combination of burning, itching, pain, and/or tenderness; the reactions were mild or moderate in intensity and lasted only a few days. CONCLUSIONS: Ingenol mebutate gel, 0.05%, had a good safety and tolerability profile when used to treat scalp actinic keratosis in patients who had a prolonged history of actinic keratosis. PMID- 27354885 TI - Efficacy and Tolerability of a Combined 445nm and 630nm Over-the-counter Light Therapy Mask with and without Topical Salicylic Acid versus Topical Benzoyl Peroxide for the Treatment of Mild-to-moderate Acne Vulgaris. AB - OBJECTIVE: To evaluate the efficacy and tolerance of a combined 445nm/630nm light therapy mask for the treatment of mild-to-moderate acne vulgaris with and without topical 1% salicylic acid with retinol versus 2.5% benzoyl peroxide. DESIGN: A 12 week evaluator-blinded, randomized study. Subjects were randomized to be treated with the 445nm/630nm light therapy mask alone, benzoyl peroxide, or 445nm/630nm light therapy mask with topical 1% salicylic acid with retinol. PARTICIPANTS: Healthy male and female subjects 12 to 35 years old with Fitzpatrick skin types I to VI and mild-to-moderate facial acne vulgaris. MEASUREMENTS: The primary endpoint was the change in the number of inflammatory acne lesions after 12 weeks of treatment. Secondary endpoints included the change in noninflammatory acne lesions, change in total acne lesions, change in Investigator Global Acne Assessments, and overall responder rate. RESULTS: 445nm/630nm light therapy mask treated subjects showed a 24.4-percent improvement in inflammatory acne lesions (p<0.01) versus 17.2 percent (p<0.05) and 22.7 percent (p<0.01) in benzoyl peroxide and 445nm/630nm light therapy mask with topical 1% salicylic acid with retinol, respectively, a 19.5-percent improvement in noninflammatory lesions (p<0.001) versus 6.3 and 4.8 percent for benzoyl peroxide and 445nm/630nm light therapy mask with topical 1% salicylic acid with retinol, respectively. Subjects in the 445nm/630nm light therapy mask group also achieved a 19.0-percent improvement in the Investigator Global Acne Assessment (p<0.001) versus 4.7 percent in benzoyl peroxide and 13.9 percent in 445nm/630nm light therapy mask with topical 1% salicylic acid with retinol (p<0.01). Treatments were well tolerated overall with trends toward less early irritation in the 445nm/630nm light therapy mask group. CONCLUSION: 445nm/630nm light therapy mask appears to be a safe and effective therapy for mild-to-moderate acne. PMID- 27354886 TI - Correlation Between the Evaluation of Pigmented Lesions by a Multi-spectral Digital Skin Lesion Analysis Device and the Clinical and Histological Features of Melanoma. AB - OBJECTIVE: To correlate Multi-spectral Digital Skin Lesion Analysis classifier scores with histopathological severity of pigmented lesions and clinical features of melanoma. DESIGN: Classifier scores were computed for 1,632 skin lesions. Dermatologists evaluated the same lesions for Asymmetry, Border Irregularity, Color variegation, Diameter >6mm, Evolution, Patient's Concern, Regression, and/or "Ugly Duckling" sign. Classifier scores were correlated to the number of clinical risk features and for six histopathological severity levels of pigmented lesions. MEASUREMENTS: Average classifier score, Welch's t-test, and chi-square analysis. RESULTS: Melanomas had higher mean classifier scores (3.5) than high grade dysplastic nevi (2.7, p=0.002), low-grade dysplastic nevi (1.7, p<0.0001), non-dysplastic nevi (1.6, p<0.0001), and benign non-melanocytic lesions (2.0, p<0.0001). Classifier score and the number of clinical risk characteristics directly correlated (Pearson coefficient 0.32, p<0.0001). CONCLUSION: Correlation of classifier scores to clinical and histological melanoma features supports the effectiveness of Multi-spectral Digital Skin Lesion Analysis in assessing the risk of pigmented lesions requiring biopsy. Optimizing outcomes of dermatologist decisions to biopsy suspicious pigmented lesions may be enhanced utilizing Multi spectral Digital Skin Lesion Analysis. PMID- 27354887 TI - Experimental Evidence in Hair Restoration Procedures: Plucked Hair Survival and Growth Rate. AB - BACKGROUND: Limitations of hair restoration procedures are the amount of hairs available and the invasiveness of follicular harvesting. OBJECTIVE: The aim of this study was to compare conventional human micrografts and plucked hair follicles in an in vitro model in order to test hair growth rates for experimentally assessing the soundness of plucked follicle use in hair transplantation procedures. METHODS AND MATERIALS: A total of 100 conventional one-hair micrografts (group A; control) and a total of 80 plucked hair follicles (group B; experimental) were obtained from 14 healthy male patients. The length of each graft was measured immediately following isolation and at the end of the 10-day culture period. The Kruskal-Wallis one-way analysis of variance by ranks test was used in order to statistically analyze the data obtained. RESULTS: A statistically significant difference was found between the growth rate of micrografts in control (mean 10-day shaft growth rate = 0.30mm) and experimental (mean 10-day shaft growth rate = 0.36mm) groups. CONCLUSION: The obtained data shows a higher plucked hair follicle growth rate compared to one-hair micrografts, which leads us to believe that plucked micrografts could be a useful and less invasive adjunct in the field of hair transplantation surgery. PMID- 27354888 TI - Activity of Dapsone versus Community and Hospital Pathogens from the CANWARD Study. AB - BACKGROUND: Topical dapsone gel is a sulfone antibiotic approved for acne treatment. No microbiology studies were conducted during dapsone gel clinical trials and it is unclear whether 1) dapsone has antimicrobial activity that may be of clinical relevance in dermatology and 2) dapsone could affect the normal microbiome of facial skin where it is most commonly applied. This study assessed the in vitro activity of dapsone versus Gram-positive and Gram-negative bacterial pathogens obtained from patients with infections. METHODS: CANWARD is a national, annual, and ongoing surveillance system to assess the patterns of antibiotic resistant pathogens in Canada. In 2014, 15 tertiary care medical centers collected 3,511 isolates from blood, respiratory tract, urine, and wounds. Antimicrobial susceptibility was assessed using CLSI broth microdilution method. RESULTS: Dapsone demonstrated relatively poor activity versus Gram-negative bacilli with most MIC50, MIC90 in the range of 512MUg/mL and >512MUg/mL, respectively. In contrast, dapsone demonstrated activity versus Gram-positive cocci, such as Staphylococcus (including methicillin-resistant S. aureus [MRSA], methicillin-sensitive S. aureus [MSSA]), Streptococcus, and Enterococcus-several strains of S. epidermidis had MICs of 32 and 64MUg/mL; there were strains of E. faecalis with MICs of 8, 16, 32, and 64MUg/mL; and several strains of S. agalactiae and S. pyogenes demonstrated dapsone MICs of 4, 8, 16, 32, and 64MUg/mL. CONCLUSION: Dapsone has demonstrated antimicrobial activity in vitro. Whether this activity is part of the mechanism of action of topical dapsone in acne remains unknown. There are limited cutaneous pharmacokinetic data with topical dapsone including skin concentrations achieved with topical dapsone therapy; however, topical dapsone as a 2% nanoemulsion has shown very high (1196 3837.34MUg/cm(2)) local skin concentrations. At these high concentrations, topical dapsone would be expected to affect the skin flora of patients with acne (especially Gram-positive cocci, such as Staphylococcus and Streptococcus). These concentrations are multiple times higher (20x-1000x) than the dapsone MICs found for many MSSA, MRSA, S. epidermidis, S. agalactiae, and S. pyogenes, any of which may be present on the skin of acne patients. Whether this results in resistance to dapsone or more importantly results in resistance to chemically unrelated antimicrobials is currently unknown. PMID- 27354889 TI - Benzocaine/Lidocaine/Tetracaine Cream: Report of Corneal Damage and Review. AB - Practitioners are increasingly using topical anesthetics in the field of dermatology. Application of topical anesthetics prior to performing dermatologic procedures has proven to decrease pain and discomfort associated with these procedures. Despite the prevalent use of topical anesthetics, there are few standard guidelines for about which products provide optimal and safest use. Adverse events are often correlated with improper application of topical anesthetics. A few case reports have cited adverse events related to the use of compounded products that the United States Food and Drug Administration has not approved, such as benzocaine, lidocaine, tetracaine. In this article, the authors report the possible ocular side effects due to the use of benzocaine, lidocaine, tetracaine. Careful attention must be paid to this compounded product, and better formulations are needed in order to prevent adverse events. PMID- 27354890 TI - Ferrofluid-associated Cutaneous Dyschromia: Discoloration of Hand and Fingers Following Accidental Exposure to Ferromagnetic Fluid. AB - BACKGROUND: Ferrofluid is a colloidal suspension that usually consists of surfactant-coated nanoparticles of magnetite (Fe3O4) in a carrier liquid. Ferromagnetic fluid forms spikes when the liquid is exposed to a magnetic field. PURPOSE: The authors describe a man who developed temporary discoloration of his right palm and fingers after accidental cutaneous contact with ferrofluid and discuss some of the current and potential applications of this unique liquid. METHODS: A 28-year-old man was evaluating the effects of magnetic fields using ferrofluid. He performed a modification of the "leaping ferrofluid" demonstration in which he held a superstrong (14,800 gauss magnetic field strength) N52 rare earth neodymium magnet in his palm and slowly lowered that hand over an open bowl that was filled with ferrofluid. RESULTS: As the magnet approached the liquid, the ferrofluid became magnetized. The liquid leaped from the bowl and contacted not only the magnet, but also the palmar surface of his hand and fingers, resulting in a black-brown dyschromia of the affected skin. The discoloration completely resolved after two weeks without any adverse sequellae. CONCLUSION: Ferrofluid has numerous current and potential applications; in addition to being of value educationally and aesthetically (after being subjected to magnetic fields), it is also utilized for audio loudspeakers, medical innovations (such as a component of either a research tool, a diagnostic aid, or a treatment modality), and seals. Although the authors' patient did not experience any acute or chronic toxicity from his cutaneous exposure to ferrofluid, conservative follow-up for individuals who experience skin contact with ferromagnetic fluid may be appropriate. PMID- 27354892 TI - Cardiomyopathy in becker muscular dystrophy: Overview. AB - Becker muscular dystrophy (BMD) is an X-linked recessive disorder involving mutations of the dystrophin gene. Cardiac involvement in BMD has been described and cardiomyopathy represents the number one cause of death in these patients. In this paper, the pathophysiology, clinical evaluations and management of cardiomyopathy in patients with BMD will be discussed. PMID- 27354891 TI - Aneuploidy in stem cells. AB - Stem cells hold enormous promise for regenerative medicine as well as for engineering of model systems to study diseases and develop new drugs. The discovery of protocols that allow for generating induced pluripotent stem cells (IPSCs) from somatic cells has brought this promise steps closer to reality. However, as somatic cells might have accumulated various chromosomal abnormalities, including aneuploidies throughout their lives, the resulting IPSCs might no longer carry the perfect blueprint for the tissue to be generated, or worse, become at risk of adopting a malignant fate. In this review, we discuss the contribution of aneuploidy to healthy tissues and how aneuploidy can lead to disease. Furthermore, we review the differences between how somatic cells and stem cells respond to aneuploidy. PMID- 27354893 TI - Thrombosis in ST-elevation myocardial infarction: Insights from thrombi retrieved by aspiration thrombectomy. AB - In patients with ST-elevation myocardial infarction, recurrent cardiovascular events still remain the main cause of morbidity and mortality, despite significant improvements in antithrombotic therapy. We sought to review data regarding coronary thrombus analysis provided by studies using manual aspiration thrombectomy (AT), and to discuss how insights from this line of investigation could further improve management of acute coronary disease. Several studies investigated the fresh specimens retrieved by AT using techniques such as traditional morphological evaluation, optical microscopy, scanning electron microscopy, magnetic resonance imaging, and immunohistochemistry. These approaches have provided a better understanding of the composition and dynamics of the human coronary thrombosis process, as well as its relationship with some clinical outcomes. Recent data signaling to new antithrombotic therapeutic targets are still emerging. PMID- 27354894 TI - Incidence and trends of cardiovascular mortality after common cancers in young adults: Analysis of surveillance, epidemiology and end-results program. AB - AIM: To describe the incidence of cardiovascular mortality (CVM) in survivors of major cancers and identify its trends over the past two decades. METHODS: We used the surveillance, epidemiology and end-results 19 registry to identify young adults (20-49 years), diagnosed with the following major primary cancers: Lung, breast, liver/intrahepatic bile duct, pancreas, prostate, colorectal, and ovarian from 1990 through 2012 and identified the cumulative incidence of CVM after adjusting for confounding factors. RESULTS: We identified a total of 301923 cancers (breast 173748, lung 38938, colorectal 31722, prostate 22848, ovary 16065, liver 9444, pancreas 9158). A total of 2297 (0.8%) of patients had incident CVM. Lung (10-year cumulative CVM 2.4%) and liver (1.73%) cancers had the highest incidence of CVM, while breast (0.6%) and prostate (1.2%) had the lowest CVM mortality, even after multiple adjustments (P < 0.001). Overall, there was a significant improvement in CVM since 1990 [2005-2012 vs 1990-1994, adjusted HR 0.63 (0.54-0.72), P < 0.001]. This was driven by improvements in CVM in lung cancers (P = 0.02), breast (P < 0.001), and a trend in ovarian cancer (P = 0.097). There was no statistically significant improvement in CVM among survivors of colorectal, pancreatic, liver, or prostate cancers. CONCLUSION: The risk of CVM differs among different cancers, and is highest among survivors of lung and liver cancers. The incidence of CVM has decreased over the past 2 decades mainly among survivors of lung and breast cancers. PMID- 27354895 TI - Asymptomatic post-rheumatic giant left atrium. AB - A 78-year-old asymptomatic woman was referred to our clinic for a second opinion regarding indication for mitral valve surgery. An echocardiogram showed a moderate mitral stenosis with a concomitant severe regurgitation. The most striking feature, however, was a giant left atrium with a parasternal anteroposterior diameter of 79 mm and a left atrial volume index of 364 mL/m2. There are various echocardiographic definitions of a giant left atrium, which are mainly based on measurements of the anteroposterior diameter of the left atrium using M-mode in the parasternal long axis view. Since the commonly accepted method for echocardiographic evaluation of left atrial size is left atrial volume index, we propose a cut-off value of 140 mL/m(2) for the definition of a "giant left atrium". PMID- 27354896 TI - Successful extracorporeal life support in sudden cardiac arrest due to coronary anomaly. AB - Extracorporeal life support (ECLS) has recently been reported to have a survival benefit in patients with cardiac arrest. It is now used widely as a lifesaving modality. Here, we describe a case of sudden cardiac arrest (SCA) in a young athlete with an anomalous origin of the right coronary artery from the left coronary sinus. Resuscitation was successful using ECLS before curative bypass surgery. We highlight the efficacy of ECLS for a patient with SCA caused by a rare, unexpected aetiology. In conclusion, ECLS was a lifesaving modality for SCA due to an anomalous coronary artery in this young patient. PMID- 27354897 TI - Perception of professional ethics by Iranian occupational therapists working with children. AB - Ethics are related to the structure and culture of the society. In addition to specialized ethics for every profession, individuals also hold their own personal beliefs and values. This study aimed to investigate Iranian occupational therapists' perception of ethical practice when working with children. For this purpose, qualitative content analysis was used and semi-structured interviews were conducted with ten occupational therapists in their convenient place and time. Each interview was transcribed and double-checked by the research team. Units of meaning were extracted from each transcription and then coded and categorized accordingly. The main categories of ethical practice when working with children included personal attributes, responsibility toward clients, and professional responsibility. Personal attributes included four subcategories: veracity, altruism, empathy, and competence. Responsibility toward clients consisted of six subcategories: equality, autonomy, respect for clients, confidentiality, beneficence, and non-maleficence. Professional responsibility included three subcategories: fidelity, development of professional knowledge, and promotion and growth of the profession. Findings of this study indicated that in Iran, occupational therapists' perception of autonomy, beneficence, non maleficence, fidelity and competence is different from Western countries, which may be due to a lower knowledge of ethics and other factors such as culture. The results of this study may be used to develop ethical codes for Iranian occupational therapists both during training and on the job. PMID- 27354899 TI - A complementary response to the article "breaching confidentiality: medical mandatory reporting laws in Iran". PMID- 27354898 TI - Surveying the attitudes of transsexual patients referring to Tehran Institute of Psychiatry toward doctors' empathy, Iran, 2011-2012. AB - Physicians' knowledge of therapy and counseling stands among the most important issues in the viewpoints of clients who refer to psychiatric centers. Transsexual patients are very important in this regard. The goal of this research is to study their attitude toward doctors' empathy. A group of transsexual patients who referred to the Tehran Institute of Psychiatry, Iran, answered the Jefferson Scale of Empathy. The relationship of the patients' age, gender, education level, and lifestyle with their attitude was measured. This study was conducted on 40 patients, including 16 women (40%) and 24 men (60%). In terms of education, 8 patients had a degree below high school diploma (20%), 9 had high school diploma (22.5%), and 23 patients were university students or of higher education level (57.5%). Among these patients, 6 were unemployed (15%), 10 were students (25%), and the rest were employed. Moreover, 8 participants lived alone (20%), 5 lived with their friends (12.5%), and 27 lived with their family (67.5%). Gender had no influence on the average score of the questionnaires, yet level of education had some influence. Lifestyle also had a significant influence on the patients' attitude. On the other hand, patients whose problems began before the age of 12 had lower score than others. Experienced psychologists in referential centers can express greater levels of empathy to specific diseases and this trend is very effective on the patients' cooperation level. In order to create an effective relationship between physicians and patients, the efficiency of the health system and increasing satisfaction of specific patients should be considered. PMID- 27354900 TI - Development of a scale for the evaluation of patients' rights prerequisites at educational hospitals in Iran: a study using the Delphi technique. AB - The patients' rights status is one of the essential elements in defining norms related to the concept of clinical governance system. In addition, the patients' rights status is an important index for quality of care offered in the health care system. However, the lack of a coherent instrument makes it difficult to evaluate patients' rights status in hospitals and clinics. The aim of this study was to develop an instrument for the evaluation of patients' rights prerequisites at educational hospitals in Iran. This study was conducted using the modified Delphi technique. In this study, 36 experts in the fields of law, medicine, and professional ethics were participated. The panel of experts participated in 3 rounds. First, experts were asked to judge some pre-identified items, and then, excluded items were judged again in the second round. At the end of the third round, all of the agreed items were included in the final list to form an evaluative scale on practice of patients' rights. Experts were asked to judge a total 171 items in 3 rounds. Around 31% (n = 53) of items obtained the panel's approval to be included in the final version of the scale. The experts' opinions were collected using face-to-face interviews and electronic email during a 6 month period of data collection from October 2013 to February 2014. This study developed a 53-item scale for evaluation of patients' rights prerequisites in educational hospitals in Iran. This scale was developed in 7 areas of commitments including university education, research, supervision, process management, physical structure, organizational policy, and human resources management. This study developed an evaluative scale to assess the practice of patients' rights in educational hospitals. The items in the final version of this scale were obtained from a consensus of experts and the instrument can be used to evaluate the context and prerequisites for practice of patients' rights in Iranian educational hospitals. PMID- 27354901 TI - Deletion and duplication of 16p11.2 are associated with opposing effects on visual evoked potential amplitude. AB - BACKGROUND: Duplication and deletion of the chromosomal region 16p11.2 cause a broad range of impairments, including intellectual disability, language disorders, and sensory symptoms. However, it is unclear how changes in 16p11.2 dosage affect cortical circuitry during development. The aim of this study was to investigate whether the visual evoked potential (VEP) could be used as a noninvasive quantitative measure of cortical processing in children with 16p11.2 copy number variation. METHODS: Pattern-reversal VEPs were successfully recorded in 19 deletion carriers, 9 duplication carriers, and 13 typically developing children between the ages of 3 and 14 years. The stimulus was a black and white checkerboard (60') that reversed contrast at 2 Hz. VEP responses were extracted from continuous EEG recorded using a high-density elasticized electrode net. RESULTS: Quantitative analysis of the VEP waveform revealed that, relative to controls, deletion carriers displayed increased amplitude and duplication carriers displayed diminished amplitude. Latencies of the VEP waveform components were unaffected by 16p11.2 status. P1 amplitude did not correlate with age, IQ, or head circumference. CONCLUSIONS: The results of this study suggest that recording VEP is a useful method to assay cortical processing in children with 16p11.2 copy number variation. There is a gene dosage-dependent effect on P1 amplitude that merits further investigation. The VEP is directly translatable to animal models, offering a promising way to probe the neurobiological mechanisms underlying cortical dysfunction in this developmental disorder. PMID- 27354903 TI - Editorial. PMID- 27354902 TI - Sex-specific effects of LiCl treatment on preservation of renal function and extended life-span in murine models of SLE: perspective on insights into the potential basis for survivorship in NZB/W female mice. AB - Considerable research effort has been invested in attempting to understand immune dysregulation leading to autoimmunity and target organ damage. In systemic lupus erythematosus (SLE), patients can develop a systemic disease with a number of organs involved. One of the major target organs is the kidney, but patients vary in the progression of the end-organ targeting of this organ. Some patients develop glomerulonephritis only, while others develop rapidly progressive end organ failure. In murine models of SLE, renal involvement can also occur. Studies performed over the past several years have indicated that treatment with LiCl of females, but not males of the NZB/W model, at an early age during the onset of disease, can prevent development of end-stage renal disease in a significant percentage of the animals. While on Li treatment, up to 80 % of the females can exhibit long-term survival with evidence of mild glomerulonephritis which does not progress to renal failure in spite of on-going autoimmunity. Stopping the treatment led to a reactivation of the disease and renal failure. Li treatment of other murine models of SLE was less effective and decreased survivorship in male BxSB mice, exhibited little effect on male MRL-lpr mice, and only modestly improved survivorship in female MRL-lpr mice. This perspective piece discusses the findings of several related studies which support the concept that protecting target organs such as the kidney, even in the face of continued immune insults and some inflammation, can lead to prolonged survival with retention of organ function. Some possible mechanisms for the effectiveness of Li treatment in this context are also discussed. However, the detailed mechanistic basis for the sex specific effects of LiCl treatment particularly in the NZB/W model remains to be elucidated. Elucidating such details may provide important clues for development of effective treatment for patients with SLE, ~90 % of which are females. PMID- 27354904 TI - Cross-sectional comparison of first-generation antipsychotic long-acting injections vs risperidone long-acting injection: patient-rated attitudes, satisfaction and tolerability. AB - OBJECTIVES: The objective of this study was to compare patients' attitudes and satisfaction with medication and patient-rated tolerability between those prescribed a first-generation antipsychotic long-acting injection (FGA-LAI) and those prescribed risperidone long-acting injection (RLAI). METHOD: A cross sectional study of a representative sample of outpatients prescribed an FGA-LAI or RLAI for a minimum of 6 months and attending a depot clinic. Attitudes to medication were assessed by the Drug Attitude Inventory (DAI-30), tolerability was measured by the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) and satisfaction with antipsychotic medication was assessed by the Satisfaction with Antipsychotic Medication (SWAM) scale. RESULTS: The RLAI (n = 28) and FGA-LAI (n = 39) groups did not differ in terms of mean age, sex, diagnosis and ethnicity. All individual LAIs were prescribed within British National Formulary limits. The most commonly prescribed FGA-LAI was flupentixol decanoate (n = 22). There was no significant difference between the RLAI and FGA LAI groups in terms of mean total scores on the DAI-30, LUNSERS and SWAM or the tolerability subscales of the LUNSERS or the two subscales (treatment acceptability and medication insight) of the SWAM. In both LAI groups there was a low level of side effects (LUNSERS) and a generally positive attitude (DAI-30) and reasonable satisfaction (SWAM) with medication. CONCLUSIONS: Patients treated with FGA-LAI and RLAI for at least 6 months did not differ in terms of patient rated tolerability, attitudes and satisfaction with medication. The current design cannot determine whether differences would have been evident earlier on during treatment. These results should be regarded as preliminary and are subject to prescribing bias. Randomized studies avoid prescribing bias and are a superior way to compare specific LAIs. Ideally randomized studies should include patient rated outcome measures including medication tolerability; assessment of side effects, efficacy and quality of life made by blinded raters; and additional objective side-effect data including changes in weight and key blood parameters. PMID- 27354905 TI - Does race affect prescribing for acute psychosis? Evaluation by a case vignette. AB - BACKGROUND: Black people are over represented in mental health services and prescribing of antipsychotics differs by race in some countries. Our previous UK research into the prescribing of antipsychotics in large, multicentre studies found no important differences for black and white patients. However, we received several comments challenging our findings. We wanted to test the validity of these anecdotes by devising two case vignettes that differed only by race and asking prescribers to choose antipsychotic treatment. METHOD: A case study was sent to all medical prescribers in the South London and Maudsley NHS Trust. Half of the prescribers for each grade of staff were sent the case study where the ethnicity of the patient was white and the other half where the ethnicity was black. Participants were asked to describe what they would prescribe for the patient. Outcomes were total percentage maximum dose, high dose, type of antipsychotic, route of administration and antipsychotic polypharmacy. RESULTS: We received 123 completed case studies and demographic data forms from prescribers. There were no differences in percentage maximum dose, high dose, type, route and number of antipsychotics prescribed by case study ethnicity. CONCLUSIONS: Prescribing for UK black and white patients is broadly similar when tested in clinical and theoretical studies. PMID- 27354906 TI - Clozapine-induced hypersalivation: an estimate of prevalence, severity and impact on quality of life. AB - OBJECTIVES: The objective of this study was to evaluate the prevalence and severity of clozapine-induced hypersalivation, and assess the impact hypersalivation has on global functioning. METHODS: Participants attending a dedicated clozapine clinic were invited to undertake a structured interview regarding their experiences of clozapine-induced hypersalivation. Two psychometric instruments to measure hypersalivation, the Nocturnal Hypersalivation Rating Scale and the Drooling Severity and Frequency Scale were used. RESULTS: Clozapine-induced hypersalivation was experienced by 92% of participants, with nocturnal hypersalivation more prevalent compared to daytime hypersalivation (85% versus 48%). Daytime drooling was severe in 18% of cases and was present on a frequent or constant basis for 20% of individuals. Hypersalivation had at least a moderate impact on the quality of life of 15% of study participants. CONCLUSIONS: Clozapine-induced hypersalivation is the most prevalent adverse effect experienced by patients treated with clozapine and negatively impacts on quality of life, particularly if daytime drooling is present. The development of further strategies to ameliorate this adverse effect is required given the demonstrated lack of success to date in managing this condition. PMID- 27354907 TI - Ketamine enantiomers in the rapid and sustained antidepressant effects. AB - Recent evidence has suggested that the N-methyl-D-aspartate receptor antagonist ketamine shows significant therapeutic effects in major depression and bipolar disorder. This effect is especially important in treatment-resistant depression and depression with suicidal ideation. In this review we explain the mechanism of action, drug efficacy, and the side effects of ketamine; the antidepressive effects of ketamine; the individual effects of ketamine isomers, R(-) ketamine and S(+) ketamine; the effects of the combination of ketamine with electroconvulsive therapy; and the possible use of ketamine in treating depression. PMID- 27354910 TI - Cabergoline-induced manic episode: case report. AB - Cabergoline is an orally administered synthetic dopamine agonist that is used for the treatment of hyperprolactinemia, Parkinson's disease and antipsychotic induced prolactin elevation. One of the main characteristics of cabergoline is its long duration of effect. It is highly effective in suppressing prolactin levels up to 21 days after a single 1 mg oral dose. The prolonged elimination half-life offers an advantage of once-daily dosing, but it might be a handicap in terms of washout of adverse effects such as psychosis. Cabergoline has been associated with adverse reactions consistent with other dopaminergic agonists including cardiovascular, gastrointestinal and neuropsychiatric effects. It is known that dopaminergic treatment is a remarkable risk factor for psychosis. A number of reports implicate dopamine agonists in the development of psychosis, but there is no knowledge in the literature of dopamine agonist-induced mania. In this case, we report the first manic episode occurring after cabergoline use for hyperprolactinemia treatment. In susceptible individuals, cabergoline can cause manic episodes and cabergoline should be used more carefully considering the risk benefit ratio. PMID- 27354908 TI - Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years. AB - To date, pharmacological treatments for mood and anxiety disorders and for drug dependence show limited efficacy, leaving a large number of patients suffering severe and persistent symptoms. Preliminary studies in animals and humans suggest that ayahuasca, psilocybin and lysergic acid diethylamide (LSD) may have antidepressive, anxiolytic, and antiaddictive properties. Thus, we conducted a systematic review of clinical trials published from 1990 until 2015, assessing these therapeutic properties. Electronic searches were performed using the PubMed, LILACS, and SciELO databases. Only clinical trials published in peer reviewed journals were included. Of these, 151 studies were identified, of which six met the established criteria. Reviewed studies suggest beneficial effects for treatment-resistant depression, anxiety and depression associated with life threatening diseases, and tobacco and alcohol dependence. All drugs were well tolerated. In conclusion, ayahuasca, psilocybin and LSD may be useful pharmacological tools for the treatment of drug dependence, and anxiety and mood disorders, especially in treatment-resistant patients. These drugs may also be useful pharmacological tools to understand psychiatric disorders and to develop new therapeutic agents. However, all studies reviewed had small sample sizes, and half of them were open-label, proof-of-concept studies. Randomized, double-blind, placebo-controlled studies with more patients are needed to replicate these preliminary findings. PMID- 27354911 TI - Genetic diversity of ruminant Pestivirus strains collected in Northern Ireland between 1999 and 2011 and the role of live ruminant imports. AB - BACKGROUND: The genus pestivirus within the family Flaviviridae includes bovine viral diarrhoea virus (BVDV) types 1 and 2, border disease virus (BDV) and classical swine fever virus. The two recognised genotypes of BVDV are divided into subtypes based on phylogenetic analysis, namely a-p for BVDV-1 and a-c for BVDV-2. METHODS: Three studies were conducted to investigate the phylogenetic diversity of pestiviruses present in Northern Ireland. Firstly, pestiviruses in 152 serum samples that had previously tested positive for BVDV between 1999 and 2008 were genotyped with a RT-PCR assay. Secondly, the genetic heterogeneity of pestiviruses from 91 serum samples collected between 2008 and 2011 was investigated by phylogenetic analysis of a 288 base pair portion of the 5' untranslated region (UTR). Finally, blood samples from 839 bovine and 4,437 ovine animals imported in 2010 and 2011 were tested for pestiviral RNA. Analysis of animal movement data alongside the phylogenetic analysis of the strains was carried out to identify any links between isolates and animal movement. RESULTS: No BVDV-2 strains were detected. All of the 152 samples in the first study were genotyped as BVDV-1. Phylogenetic analysis indicated that the predominant subtype circulating was BVDV-1a (86 samples out of 91). The remaining five samples clustered close to reference strains in subtype BVDV-1b. Out of the imported animals, 18 bovine samples tested positive and 8 inconclusive (Ct >=36), while all ovine samples were negative. Eight sequences were obtained and were defined as BVDV-1b. Analysis of movement data between herds failed to find links between herds where BVDV-1b was detected. CONCLUSION: Given that only BVDV-1a was detected in samples collected between 1968 and 1999, this study suggests that at least one new subtype has been introduced to Northern Ireland between 1999 and 2011 and highlights the potential for importation of cattle to introduce new strains. PMID- 27354909 TI - Lysergic acid diethylamide: a drug of 'use'? AB - Lysergic acid diethylamide (LSD), described as a classical hallucinogen, began its journey from the middle of the last century following an accidental discovery. Since then, it was used as a popular and notorious substance of abuse in various parts of the world. Its beneficial role as an adjunct to psychotherapy was much unknown, until some 'benevolent' experiments were carried out over time to explore some of its potential uses. But, many of its effects were unclear and seemed to be a psychedelic enigma. In this review article, we have described the receptor pharmacology, mechanism of action, effects and adverse effects of LSD on the normal body system. We have also highlighted its addictive potentials and the chances of developing tolerance. We have assimilated some of the interesting therapeutic uses of this drug, such as an antianxiety agent, a creativity enhancer, a suggestibility enhancer, and a performance enhancer. We have also described LSD to be successfully used in drug and alcohol dependence, and as a part of psychedelic peak therapy in terminally ill patients. The relevant chronological history and literature in the light of present knowledge and scenarios have been discussed. Based on available evidence, LSD could be tried therapeutically in certain specific conditions under controlled settings. But as we mention, due to all the safety concerns, the use of this nonaddictive 'entheogen' in actual practice warrants a lot of expertise, caution, cooperation and ethical considerations. PMID- 27335634 TI - Immunoblotting validation of research antibodies generated against HS1-associated protein X-1 in the human neutrophil model cell line PLB-985. AB - HS1-associated protein X-1 (Hax1) is a 35 kDa protein that is ubiquitously expressed. Hax1 is an anti-apoptotic protein with additional roles in cell motility, and autosomal recessive loss of Hax1 results in Kostmann syndrome, a form of severe congenital neutropenia. Because of the important role of Hax1 in neutrophils we demonstrate here validation of two commercially available research antibodies directed against human Hax1 in the human myeloid leukemia cell line PLB-985 cells. We show that both the mouse anti-Hax1 monoclonal IgG directed against amino acids 10-148 of Hax1 and a rabbit anti-Hax1 polyclonal IgG antibody directed against full-length Hax1 reliably and consistently detect Hax1 during immunoblotting of three different PLB-985 cell densities. Using shRNA mediated Hax1 knockdown, we demonstrate the specificity of both Hax1 antibodies. In addition, our results suggest that the rabbit anti-Hax1 polyclonal antibody provides a stronger intensity in detecting Hax1 protein, with detection in as few as 0.1 x 10 (6) cells in 6 total replicates we have performed. PMID- 27347374 TI - IL-6 stimulates a concentration-dependent increase in MCP-1 in immortalised human brain endothelial cells. AB - Systemic inflammation is associated with neurodegeneration, with elevated interleukin-6 (IL-6) in particular being correlated with an increased risk of dementia. The brain endothelial cells of the blood brain barrier (BBB) serve as the interface between the systemic circulation and the brain microenvironment and are therefore likely to be a key player in the development of neuropathology associated with systemic inflammation. Endothelial cells are known to require soluble IL-6 receptor (sIL-6R) in order to respond to IL-6, but studies in rat models have shown that this is not the case for brain endothelial cells and studies conducted in human cells are limited. Here we report for the first time that the human cerebral microvascular cell line, hCMVEC, uses the classical mIL 6R signalling pathway in response to IL-6 in a concentration-dependent manner as measured by the production of monocyte chemotactic protein (MCP-1). This novel finding highlights a unique characteristic of human brain endothelial cells and that further investigation into the phenotype of this cell type is needed to elucidate the mechanisms of BBB pathology in inflammatory conditions. PMID- 27347377 TI - Lovastatin lactone may improve irritable bowel syndrome with constipation (IBS-C) by inhibiting enzymes in the archaeal methanogenesis pathway. AB - Methane produced by the methanoarchaeon Methanobrevibacter smithii ( M. smithii) has been linked to constipation, irritable bowel syndrome with constipation (IBS C), and obesity. Lovastatin, which demonstrates a cholesterol-lowering effect by the inhibition of HMG-CoA reductase, may also have an anti-methanogenesis effect through direct inhibition of enzymes in the archaeal methanogenesis pathway. We conducted protein-ligand docking experiments to evaluate this possibility. Results are consistent with recent clinical findings. METHODS: F420-dependent methylenetetrahydromethanopterin dehydrogenase ( mtd), a key methanogenesis enzyme was modeled for two different methanogenic archaea: M. smithii and Methanopyrus kandleri. Once protein models were developed, ligand-binding sites were identified. Multiple ligands and their respective protonation, isomeric and tautomeric representations were docked into each site, including F420-coenzyme (natural ligand), lactone and beta-hydroxyacid forms of lovastatin and simvastatin, and other co-complexed ligands found in related crystal structures. RESULTS: 1) Generally, for each modeled site the lactone form of the statins had more favorable site interactions compared to F420; 2) The statin lactone forms generally had the most favorable docking scores, even relative to the native template PDB ligands; and 3) The statin beta-hydroxyacid forms had less favorable docking scores, typically scoring in the middle with some of the F420 tautomeric forms. Consistent with these computational results were those from a recent phase II clinical trial ( NCT02495623) with a proprietary, modified-release lovastatin lactone (SYN-010) in patients with IBS-C, which showed a reduction in symptoms and breath methane levels, compared to placebo. CONCLUSION: The lactone form of lovastatin exhibits preferential binding over the native-F420 coenzyme ligand in silico and thus could inhibit the activity of the key M. smithii methanogenesis enzyme mtd in vivo. Statin lactones may thus exert a methane-reducing effect that is distinct from cholesterol lowering activity, which requires HMGR inhibition by statin beta-hydroxyacid forms. PMID- 27354915 TI - Association between heat stress and oxidative stress in poultry; mitochondrial dysfunction and dietary interventions with phytochemicals. AB - Heat as a stressor of poultry has been studied extensively for many decades; it affects poultry production on a worldwide basis and has significant impact on well-being and production. More recently, the involvement of heat stress in inducing oxidative stress has received much interest. Oxidative stress is defined as the presence of reactive species in excess of the available antioxidant capacity of animal cells. Reactive species can modify several biologically cellular macromolecules and can interfere with cell signaling pathways. Furthermore, during the last decade, there has been an ever-increasing interest in the use of a wide array of natural feed-delivered phytochemicals that have potential antioxidant properties for poultry. In light of this, the current review aims to (1) summarize the mechanisms through which heat stress triggers excessive superoxide radical production in the mitochondrion and progresses into oxidative stress, (2) illustrate that this pathophysiology is dependent on the intensity and duration of heat stress, (3) present different nutritional strategies for mitigation of mitochondrial dysfunction, with particular focus on antioxidant phytochemicals. Oxidative stress that occurs with heat exposure can be manifest in all parts of the body; however, mitochondrial dysfunction underlies oxidative stress. In the initial phase of acute heat stress, mitochondrial substrate oxidation and electron transport chain activity are increased resulting in excessive superoxide production. During the later stage of acute heat stress, down-regulation of avian uncoupling protein worsens the oxidative stress situation causing mitochondrial dysfunction and tissue damage. Typically, antioxidant enzyme activities are upregulated. Chronic heat stress, however, leads to downsizing of mitochondrial metabolic oxidative capacity, up regulation of avian uncoupling protein, a clear alteration in the pattern of antioxidant enzyme activities, and depletion of antioxidant reserves. Some phytochemicals, such as various types of flavonoids and related compounds, were shown to be beneficial in chronic heat-stressed poultry, but were less or not effective in non-heat-stressed counterparts. This supports the contention that antioxidant phytochemicals have potential under challenging conditions. Though substantial progress has been made in our understanding of the association between heat stress and oxidative stress, the means by which phytochemicals can alleviate oxidative stress have been sparsely explored. PMID- 27354916 TI - Disrupted white matter integrity is associated with cognitive deficits in patients with amnestic mild cognitive impairment: An atlas-based study. AB - OBJECTIVE: This study investigated white matter integrity in patients with amnestic mild cognitive impairment by diffusion tensor imaging. METHODS: A total of 83 patients with amnestic mild cognitive impairment and 85 elderly healthy controls underwent neuropsychological testing and a diffusion tensor imaging scan. Whole-brain white matter data were parcellated into 50 regions based on the anatomical ICBM-DTI-81 atlas, and regional diffusion metrics consisting of fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were calculated for each region. Diffusion tensor imaging indices were compared between groups, and it was determined that between-group differences were significantly correlated with neurocognitive performance. RESULTS: Relative to the healthy controls group, the amnestic mild cognitive impairment group exhibited poorer cognitive performance in all neuropsychological tests except the complex figure test (p = 0.083) and showed decreased mean fractional anisotropy in the fornix, increased mean diffusivity in the fornix and bilateral uncinate fasciculus, elevated axial diffusivity in the fornix and genu of corpus callosum, and elevated radial diffusivity in the fornix and bilateral uncinate fasciculus (p < 0.05). Behaviorally, integrity of the bilateral uncinate fasciculus was correlated positively with episodic memory function, while left uncinate fasciculus integrity was positively associated with language function in the amnestic mild cognitive impairment group (p < 0.05). CONCLUSION: White matter abnormalities in neural pathways associated with memory were correlated with neurocognitive deficiencies in amnestic mild cognitive impairment. Given that amnestic mild cognitive impairment is putatively a prodromal syndrome for Alzheimer's disease, this study furthers our understanding of the white matter changes associated with Alzheimer's disease pathogenesis in the predementia stage. PMID- 27354917 TI - The effect of pharmacist-led interventions in optimising prescribing in older adults in primary care: A systematic review. AB - OBJECTIVE: To evaluate studies of pharmacist-led interventions on potentially inappropriate prescribing among community-dwelling older adults receiving primary care to identify the components of a successful intervention. DATA SOURCES: An electronic search of the literature was conducted using the following databases from inception to December 2015: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, MEDLINE (through Ovid), Trip, Centre for Reviews and Dissemination databases, Cochrane Database of Systematic Reviews, ISI Web of Science, ScienceDirect, ClinicalTrials.gov, metaRegister of Controlled Trials, ProQuest Dissertations & Theses Database (Theses in Great Britain, Ireland and North America). REVIEW METHODS: Studies were included if they were randomised controlled trials or quasi-randomised studies involving a pharmacist-led intervention compared to usual/routine care which aimed to reduce potentially inappropriate prescribing in older adults in primary care. Methodological quality of the included studies was independently assessed. RESULTS: A comprehensive literature search was conducted which identified 2193 studies following removal of duplicates. Five studies met the inclusion criteria. Four studies involved a pharmacist conducting a medication review and providing feedback to patients or their family physician. One randomised controlled trial evaluated the effect of a computerised tool that alerted pharmacists when elderly patients were newly prescribed potentially inappropriate medications. Four studies were associated with an improvement in prescribing appropriateness. CONCLUSION: Overall, this review demonstrates that pharmacist-led interventions may improve prescribing appropriateness in community-dwelling older adults. However, the quality of evidence is low. The role of a pharmacist working as part of a multidisciplinary primary care team requires further investigation to optimise prescribing in this group of patients. PMID- 27354918 TI - Numidum massiliense gen. nov., sp. nov., a new member of the Bacillaceae family isolated from the human gut. AB - Numidum massiliense gen. nov., sp. nov., strain mt3(T) is the type strain of Numidum gen. nov., a new genus within the family Bacillaceae. This strain was isolated from the faecal flora of a Tuareg boy from Algeria. We describe this Gram-positive facultative anaerobic rod and provide its complete annotated genome sequence according to the taxonogenomics concept. Its genome is 3 755 739 bp long and contains 3453 protein-coding genes and 64 RNA genes, including eight rRNA genes. PMID- 27354919 TI - Indigenous obesity in the news: a media analysis of news representation of obesity in Australia's Indigenous population. AB - BACKGROUND: High rates of obesity are a significant issue amongst Indigenous populations in many countries around the world. Media framing of issues can play a critical role in shaping public opinion and government policy. A broad range of media analyses have been conducted on various aspects of obesity, however media representation of Indigenous obesity remains unexplored. In this study we investigate how obesity in Australia's Indigenous population is represented in newsprint media coverage. METHOD: Media articles published between 2007 and 2014 were analysed for the distribution and extent of coverage over time and across Indigenous and mainstream media sources using quantitative content analysis. Representation of the causes and solutions of Indigenous obesity and framing in text and image content was examined using qualitative framing analysis. RESULTS: Media coverage of Indigenous obesity was very limited with no clear trends in reporting over time or across sources. The single Indigenous media source was the second largest contributor to the media discourse of this issue. Structural causes/origins were most often cited and individual solutions were comparatively overrepresented. A range of frames were employed across the media sources. All images reinforced textual framing except for one article where the image depicted individual factors whereas the text referred to structural determinants. CONCLUSION: This study provides a starting point for an important area of research that needs further investigation. The findings highlight the importance of alternative news media outlets, such as The Koori Mail, and that these should be developed to enhance the quality and diversity of media coverage. Media organisations can actively contribute to improving Indigenous health through raising awareness, evidence-based balanced reporting, and development of closer ties with Indigenous health workers. PMID- 27354920 TI - Multiple genetically engineered humanized microenvironments in a single mouse. AB - BACKGROUND: Immunodeficient mouse models that accept human cell and tissue grafts can contribute greater knowledge to human stem cell research. In this technical report, we used biomaterial implants seeded with genetically engineered stromal cells to create several unique microenvironments in a single mouse. The scope of study was focused on human CD34 hematopoietic stem/progenitor cell (HSPC) engraftment and differentiation within the engineered microenvironment. RESULTS: A mouse model system was created using subdermal implant sites that overexpressed a specific human cytokines (Vascular Endothelial Growth Factor A (hVEGFa), Stromal Derived Factor 1 Alpha (hSDF1a), or Tumor Necrosis Factor Alpha (hTNFa)) by stromal cells in a three-dimensional biomaterial matrix. The systemic exposure of locally overexpressed cytokines was minimized by controlling the growth of stromal cells, which led to autonomous local, concentrated sites in a single mouse for study. This biomaterial implant approach allowed for the local analysis of each cytokine on hematopoietic stem cell recruitment, engraftment and differentiation in four different tissue microenvironments in the same host. The engineered factors were validated to have bioactive effects on human CD34+ hematopoietic progenitor cell differentiation. CONCLUSIONS: This model system can serve as a new platform for the study of multiple human proteins and their local effects on hematopoietic cell biology for in vivo validation studies. PMID- 27354922 TI - Diagnosing Disorder of Consciousness: The Opening of Pandora's Box! PMID- 27354923 TI - The Drug Trend Conundrum. PMID- 27354921 TI - Successful Management of Two Cases of Placenta Accreta and a Literature Review: Use of the B-Lynch Suture and Bilateral Uterine Artery Ligation Procedures. AB - INTRODUCTION: Placenta accreta is an increasingly common complication of pregnancy that can result in massive hemorrhage. CASE PRESENTATION: We describe two cases of placenta accreta, with successful conservative management in a referral hospital in Tehran, Iran. In both cases, two procedures were performed: compression suture (B-Lynch) and a perfusion-decreasing procedure (bilateral uterine artery ligation). We also present the results of a narrative literature review. CONCLUSIONS: The double B-Lynch and uterine arterial ligation procedure in cases of abnormal placentation might be strongly considered in fertility preservation, coagulopathy, coexisting medical disease, blood access shortage, low surgical experience, distant local hospitals, and no help. PMID- 27354925 TI - Medical Marijuana for Epilepsy? AB - Treatment-refractory epilepsy remains an important clinical problem. There is considerable recent interest by the public and physicians in using medical marijuana or its derivatives to treat seizures. The endocannabinoid system has a role in neuronal balance and ictal control. There is clinical evidence of success in diminishing seizure frequencies with cannabis derivatives, but also documentation about exacerbating epilepsy or of no discernible effect. There are lay indications and anecdotal reports of success in attenuating the severity of epilepsy, but without solid investigational corroboration. Marijuana remains largely illegal, and may induce adverse consequences. Clinical applications are not approved, thus are restricted and only recommended in selected treatment unresponsive cases, with appropriate monitoring. PMID- 27354924 TI - WHY NOT POT?: A Review of the Brain-based Risks of Cannabis. AB - In this review, we provide a historical perspective on marijuana, and survey contemporary research investigating its potential negative effects on the brain. We discuss the evidence regarding cannabis dependence, driving under the influence of cannabis, underachievement, inducing (or worsening) certain psychiatric conditions, and the potential for progression to use of more dangerous drugs-summarized by the acronym DDUMB, a cognitive tool that may help healthcare providers in their risk/benefit discussions with patients who use cannabis. We also review and discuss the impact of marijuana use on target populations, including adolescents (who are at increased risk of harm); heavy users; and people suffering from-or at high risk of- mental illness. While cannabis presents certain subjective, healthrelated, and pecuniary benefits to users, growers, and other entities, it is also associated with several brainbased risks. Understanding these risks aids clinicians and their patients in making informed and balanced decisions regarding the initiation or continuance of marijuana use. PMID- 27354926 TI - Inter-rater Reliability Assessment of ASPECT-R: (A Study Pragmatic-Explanatory Characterization Tool-Rating). AB - OBJECTIVE: The increasing importance of real-world data for clinical and policy decision making is driving a need for close attention to the pragmatic versus explanatory features of trial designs. ASPECT-R (A Study Pragmatic-Explanatory Characterization Tool-Rating) is an instrument informed by the PRECIS tool, which was developed to assist researchers in designing trials that are more pragmatic or explanatory. ASPECT-R refined the PRECIS domains and includes a detailed anchored rating system. This analysis established the inter-rater reliability of ASPECT-R. DESIGN: Nine raters (identified from a convenience sample of persons knowledgeable about psychiatry clinical research/study design) received ASPECT-R training materials and 12 study publications. Selected studies assessed antipsychotic treatment in schizophrenia, were published in peer-reviewed journals, and represented a range of studies across a pragmatic-explanatory continuum as determined by authors (CB/LA). After completing training, raters reviewed the 12 studies and rated the study domains using ASPECT-R. Intraclass correlation coefficients were estimated for total and domain scores. Qualitative ratings then were assigned to describe the inter-rater reliability. RESULTS: ASPECT-R scores for the 12 studies were completed by seven raters. The ASPECT-R total score intraclass correlation coefficient was 0.87, corresponding to an excellent inter-rater reliability. Domain intraclass correlation coefficients ranged from 0.85 to 0.31, corresponding to excellent to poor inter-rater reliability. CONCLUSION: The inter-rater reliability of the ASPECT-R total score was excellent, with excellent to good inter-rater reliability for most domains. The fair to poor inter-rater reliability for two domains may reflect a need for improved domain definition, anchoring, or training materials. ASPECT-R can be used to help understand the pragmaticexplanatory nature of completed or planned trials. PMID- 27354928 TI - Managing the Suicidal Patient in a Split-treatment Relationship. PMID- 27354927 TI - A Case of Transient Global Amnesia: A Review and How It May Shed Further Insight into the Neurobiology of Delusions. AB - Transient global amnesia is a clinical syndrome characterized by the sudden onset of anterograde amnesia, accompanied by repetitive questioning, sometimes with a retrograde component, lasting up to 24 hours, without compromise of other neurologic function. Neuroimaging after an acutetransient global amnesia event often shows transient perturbation of specific hippocampal circuits that are involved in memory processing. Critical clinical distinctions, such as between transient global amnesia and other forms of transient amnesic episodes, as well as important clues to the underlying pathophysiologies are herein reviewed. Finally, we discuss the role of hippocampal insufficiency in the neurobiology of delusions. PMID- 27354929 TI - Runny nose sign: Sequential rhinorrhea and syncope in dementia with Lewy bodies. PMID- 27354931 TI - Multiple Unilateral Vestibular Schwannomas: Segmental NF2 or Sporadic Occurrence? AB - OBJECTIVE: To report a case of a patient presenting with two separate unilateral vestibular schwannomas (VSs) without other stigmata of neurofibromatosis type 2 (NF2). STUDY DESIGN: This article discusses a case report and review of the literature. SETTING: Tertiary academic referral center. PARTICIPANTS: A 41-year old female was referred for evaluation of a left-sided 1.8-cm cerebellopontine angle tumor centered on the porus acusticus and a separate ipsilateral 3-mm intracanalicular tumor appearing to arise from the superior vestibular nerve. The patient denied a family history of NF2. Neurotologic examination was unremarkable and close review of magnetic resonance imaging did not find any other stigmata of NF2. RESULTS: The patient underwent left-sided retrosigmoid craniotomy with gross total resection of both tumors. Final pathology confirmed benign schwannoma. The INI1/SMARCB1 staining pattern did not suggest NF2 or schwannomatosis. CONCLUSIONS: This is only the third report of a case with multiple unilateral VSs occurring in a patient without other features of NF2. Herein, the authors review the two other reports and discuss potential mechanisms for this rare phenomenon. PMID- 27354930 TI - Efficacy of Intraperitoneal Administration of PEGylated NELL-1 for Bone Formation. AB - Systemically delivered NEL-like molecule-1 (NELL-1), a potent pro-osteogenic protein, promotes bone formation in healthy and osteoporotic mouse models. PEGylation of NELL-1 (NELL-PEG) increases the half-life of the protein in a mouse model without compromising its osteogenic potential, thereby improving its pharmacokinetics upon systemic delivery. This study consists of a twofold approach: a biodistribution test and an in vivo osteogenic potential test. The biodistribution test compared two commonly used administration methods for drug delivery other than intravenous-intraperitoneal (IP) and subcutaneous (SC)-to examine NELL-PEG biodistribution in mice. Compared to a single-dose SC injection (1.25 mg/kg), a single-dose IP administration yielded a higher protein uptake in the targeted bone sites. When the IP injection dose was doubled to 2.5 mg/kg, the protein remained in the femurs, tibias, and vertebrae for up to 72 h. Next, based on the results of the biodistribution study, IP administration was selected to further investigate the in vivo osteogenic effects of weekly NELL-PEG injection (q7d). In vivo, the IP administered NELL-PEG group showed significantly greater bone mineral density, bone volume fraction, and trabecular bone formation in the targeted bone sites compared to the phosphate-buffered saline control. In summary, weekly NELL-PEG injection via IP administration successfully enhanced the overall bone quality. These findings demonstrate that systemic delivery of NELL-PEG via IP administration may serve as an effective osteogenic therapy for preventing and treating osteoporosis. PMID- 27354932 TI - Malassezia pachydermatis fungemia in an adult with multibacillary leprosy. AB - Malassezia pachydermatis is a relatively rare agent of bloodstream infections. We describe an unusual case of Malassezia fungemia in an adult patient hospitalized for Staphylococcus aureus bacteremia who was also found to have multibacillary leprosy. Treatment of the patient required extensive medical management but resulted in a good outcome. PMID- 27354933 TI - Unsung heroes: Genomic successes in the developing world. PMID- 27354934 TI - Pharmacogenomics for infectious diseases in sub-Saharan Africa: Successes and opportunities. PMID- 27354935 TI - Limited resources of genome sequencing in developing countries: Challenges and solutions. AB - The differences between countries in national income, growth, human development and many other factors are used to classify countries into developed and developing countries. There are several classification systems that use different sets of measures and criteria. The most common classifications are the United Nations (UN) and the World Bank (WB) systems. The UN classification system uses the UN Human Development Index (HDI), an indicator that uses statistic of life expectancy, education, and income per capita for countries' classification. While the WB system uses gross national income (GNI) per capita that is calculated using the World Bank Atlas method. According to the UN and WB classification systems, there are 151 and 134 developing countries, respectively, with 89% overlap between the two systems. Developing countries have limited human development, and limited expenditure in education and research, among several other limitations. The biggest challenge facing genomic researchers and clinicians is limited resources. As a result, genomic tools, specifically genome sequencing technologies, which are rapidly becoming indispensable, are not widely available. In this report, we explore the current status of sequencing technologies in developing countries, describe the associated challenges and emphasize potential solutions. PMID- 27354936 TI - Tau protein as a biomarker for asphyxia: A possible forensic tool? AB - Asphyxial death has been a problem for forensic investigations due to the absence of a validated biomarker for the diagnosis of this event. Recently, research on brain affection by asphyxia raised hopes on the possible use of CNS markers for asphyxia. The cytoskeletal proteins seem to be attractive targets as they are vulnerable to hypoxia and can be affected in asphyxial deaths. Tau, an important cytoskeletal protein, showed affection in many neurodegenerative disorders and recently in some acute incidences like trauma and brain ischemia. In this report we show the affection of the normal pattern of tau and pathological aggregates of tau in the case of brain hypoxia. This may give new clues to asphyxial death investigations. PMID- 27354938 TI - SeeHaBITaT: A server on bioinformatics applications for Tospoviruses and other species. AB - Plant viruses are important limiting factors in agricultural productivity. Tospovirus is one of the severe plant pathogens, causing damage to economically important food and ornamental crops worldwide through thrips as vectors. Database application resources exclusively on this virus would help to design better control measures, which aren't available. SeeHaBITaT is a unique and exclusive web based server providing work bench to perform computational research on tospoviruses and its species. SeeHaBITaT hosts Tospoviruses specific database Togribase, MOLBIT, SRMBIT and SS with PDB. These applications would be of immense help to the Tospovirus scientific community. The server could be accessed at http://bit.srmuniv.ac.in/. PMID- 27354937 TI - Proceedings of a Sickle Cell Disease Ontology workshop - Towards the first comprehensive ontology for Sickle Cell Disease. AB - Sickle cell disease (SCD) is a debilitating single gene disorder caused by a single point mutation that results in physical deformation (i.e. sickling) of erythrocytes at reduced oxygen tensions. Up to 75% of SCD in newborns world-wide occurs in sub-Saharan Africa, where neonatal and childhood mortality from sickle cell related complications is high. While SCD research across the globe is tackling the disease on multiple fronts, advances have yet to significantly impact on the health and quality of life of SCD patients, due to lack of coordination of these disparate efforts. Ensuring data across studies is directly comparable through standardization is a necessary step towards realizing this goal. Such a standardization requires the development and implementation of a disease-specific ontology for SCD that is applicable globally. Ontology development is best achieved by bringing together experts in the domain to contribute their knowledge. The SCD community and H3ABioNet members joined forces at a recent SCD Ontology workshop to develop an ontology covering aspects of SCD under the classes: phenotype, diagnostics, therapeutics, quality of life, disease modifiers and disease stage. The aim of the workshop was for participants to contribute their expertise to development of the structure and contents of the SCD ontology. Here we describe the proceedings of the Sickle Cell Disease Ontology Workshop held in Cape Town South Africa in February 2016 and its outcomes. The objective of the workshop was to bring together experts in SCD from around the world to contribute their expertise to the development of various aspects of the SCD ontology. PMID- 27354939 TI - Implementation of genomic medicine in Sri Lanka: Initial experience and challenges. AB - The recent advances in next generation sequencing technologies have made it possible to implement genomic medicine in developing countries such as Sri Lanka where capacity for utilization is limited. This paper aims to describe our initial experience and challenges faced in integrating genomic medicine into routine clinical practice. Using the Illumina MiSeq Next generation sequencing (NGS) platform and an in-house developed bioinformatics pipeline/workflow, we successfully implemented clinical exome sequencing for rare disorders, complex disorders with unusual coexisting phenotypes, and multigene cancer panel testing for inherited cancer syndromes. The advantages of implementing these tests, the challenges for bioinformatics analysis and reporting, the ethical, legal, and social implications of moving from genetic to genomic counseling, and special policy issues related to implementing these tests are further discussed. The implementation of genomic medicine into our routine clinical practice has facilitated improved care for our patients, attesting to the ability of resource limited countries to improve care using advanced genomic technology. PMID- 27354940 TI - Translating translational medicine into global health equity: What is needed? AB - While genomics, and other omics, research is rapidly advancing in the US and Europe, progress has been slower in less resourced countries. The imbalance has given rise to concern about whether the benefits of these advances, namely new and better tests, treatments, risk identification, and prevention strategies, will be shared and available to those living in less resourced reaches of the globe. In effort to give voice to researchers, an informal survey about barriers to advancing translational medicine was administered to attendees of the 11th Asia Pacific Conference on Human Genetics, 2015, Hanoi. The overall goal of the survey was to identify unmet needs and rank their importance. Most attendees completed the survey. Not surprisingly funding is indicated as a major need. Respondents reported that lack of bioinformatics and computational tools, trained data scientists and access to datasets is creating a significant lag behind better resourced regions. Results are intended to inform efforts to create a regional consensus statement of need. Such a regional statement could help funding organizations and policy makers seeking to promote global genomics benefit sharing. PMID- 27354941 TI - Extensive Arthroscopic Chondroplasty for Cartilage Hyperplasia of the Femoral Condyle Causing Recurrent Knee Locking in a Patient With Multiple Epiphyseal Dysplasia. AB - Multiple epiphyseal dysplasia is a genetically heterogeneous group of diseases causing altered enchondral ossification. It may affect the knee, among other joints, with variable clinical manifestations. In this report, we present a case of a young adult patient with multiple epiphyseal dysplasia, presenting recurrent catching and locking of the knee due to hyperplastic irregular cartilage. Although radiographs and magnetic resonance imaging of his knee were inconclusive with regard to the source of symptoms, arthroscopic examination revealed a flap of irregular and extensive hypertrophic cartilage of the medial femoral condyle that was causing catching during knee motions. This was treated by extensive arthroscopic resection of the hypertrophic cartilage with the knee held in a deep flexion position and symptoms resolved uneventfully. The case emphasizes the importance of a thorough arthroscopic examination when radiographs and magnetic resonance imaging may overlook the specific source for symptoms, and shows the potential for symptom resolution by arthroscopic intervention in these unusual circumstances. PMID- 27354942 TI - Technique of Arthroscopic Treatment of Impingement After Total Ankle Arthroplasty. AB - Rates of medial and/or lateral gutter impingement after total ankle replacement are not insignificant. If impingement should occur, it typically arises an average of 17 months after total ankle replacement. Our patient underwent treatment for right ankle medial gutter bony impingement with arthroscopic debridement 5 years after her initial total ankle replacement. Standard anteromedial and anterolateral portals and a 30 degrees 2.7-mm-diameter arthroscope were used. An aggressive soft-tissue and bony resection was performed using a combination of curettes, a 3.5-mm shaver, a 5.5-mm unsheathed burr, a drill, and a radiofrequency ablator. This case shows that arthroscopic treatment is an effective and potentially advantageous alternative to open treatment of impingement after total ankle replacement. In addition, symptoms of impingement often improve in a short amount of time after arthroscopic debridement of the medial and/or lateral gutter. PMID- 27354943 TI - Combined Anterior and Anterolateral Stabilization of the Knee With the Iliotibial Band. AB - Interest and knowledge on the anatomy, function, and biomechanical properties of the anterolateral ligament has led to the recognition of the importance of this structure in rotational control of the knee. This article describes a technique that allows for a combined anterior cruciate ligament (ACL) and anterolateral reconstruction, using an Iliotibial band (ITB) autograft. The graft is detached from the vastus lateralis from proximal to distal, at the center portion from ITB, preserving its distal insertion on the Gerdy tubercle. Its width is 1 cm for the distal part, used for the anterolateral ligament reconstruction, and 3 cm for the proximal part. An outside-in femoral tunnel is drilled respecting both the preferred favorable isometric femoral insertion site and the femoral ACL footprint. An ACL reconstruction combined with a lateral tenodesis with a continuous ITB graft respects the anatomical and isometric rules providing superior internal rotational control of the knee in comparison with a stand-alone ACL reconstruction. PMID- 27354944 TI - Reconstruction of Focal Femoral Head Cartilage Defects With a Chitin-Based Scaffold. AB - It is well known that articular cartilage defects have little capability to heal. For grade III or IV cartilage defects, surgical intervention may be required for symptomatic patients. Microfracture is a commonly used surgical technique to address these injuries. However, microfracture has drawbacks, which include the risk of ossification of the newly formed tissue, as well as the imperfect and fragile nature of the fibrous cartilage. Given the challenges associated with microfracture, BST-CarGel (Piramal Healthcare, Laval, Quebec, Canada) has been developed to stabilize and support the nascent clot. This chitin-based polymer is mixed with the patient's own blood and inserted onto the microfractured defect. The polymer allows normal clot formation and provides a matrix to strengthen the clot, prevent retraction, and increase its adhesiveness to the natural tissue. We present, with a video example, a detailed arthroscopic technique for using BST CarGel to fill a focal femoral head cartilage defect. PMID- 27354945 TI - Arthroscopic Stabilization for Chronic Latent Syndesmotic Instability. AB - Subtle syndesmotic instability not evident on radiography can result in chronic ankle pain. The diagnosis is uncommon, and arthroscopic evaluation remains the gold standard for diagnosis. Definitive surgical management can be performed at the time of diagnosis. Patients with 2 to 4 mm of diastasis of the syndesmosis or translation can be treated with debridement alone, and patients with 4 mm or more of diastasis or translation can be treated with arthroscopic debridement and reduction followed by percutaneous stabilization. Percutaneous stabilization is accomplished by a TightRope technique, which involves passing 1 or 2 suture buttons through all 4 cortices of the distal tibia and fibula. This technique is used in lieu of the traditional syndesmotic screw, which requires a subsequent operation for removal. PMID- 27354946 TI - Anterior Cruciate Ligament Reconstruction Using Hamstring Tendon Autograft With Preserved Insertions. AB - We present a technique for anterior cruciate ligament (ACL) reconstruction using hamstring tendon autograft with preserved tibial insertions. The tendons, harvested with an open-ended tendon stripper while their tibial insertions are preserved, are looped around to prepare a quadrupled graft. The femoral tunnel is drilled independently through a transportal technique, whereas the tibial tunnel is drilled in a standard manner. The length of the quadrupled graft and loop of the RetroButton is adjusted so that it matches the calculated length of both tunnels and the intra-articular part of the proposed ACL graft. After the RetroButton is flipped, the graft is manually tensioned with maximal stretch on the free end, which is then sutured to the other end with preserved insertions. We propose that preserving the insertions is more biological and may provide better proprioception. The technique eliminates the need for a tibial-side fixation device, thus reducing the cost of surgery. Furthermore, tibial-side fixation of the free graft is the weakest link in the overall stiffness of the reconstructed ACL, and this technique circumvents this problem. Postoperative mechanical stability and functional outcome with this technique need to be explored and compared with those of ACL reconstruction using free hamstring autograft. PMID- 27354947 TI - Endoscopy-Assisted Periacetabular Osteotomy. AB - Minimizing soft tissue dissection and improving visualization of vital structures during periacetabular osteotomy (PAO) is of paramount importance to improve patient outcome and minimize complications. The endoscopy-assisted PAO was introduced to accomplish this objective. It involves an initial hip arthroscopy, for treatment of central compartment pathology, followed by a mini-open Bernese periacetabular osteotomy under fluoroscopic and endoscopic guidance, and completed by final dynamic hip arthroscopy to assess acetabular reorientation and fixation and to perform femoroplasty in relation to the new acetabular rim position, if needed. Endoscopy-assisted PAO is used to treat dysplasia or acetabular retroversion in a minimally invasive fashion. PMID- 27354948 TI - Arthroscopic Reduction and Stabilization of Chronic Perilunate Wrist Dislocations. AB - An acute perilunate wrist injury that is unreduced for more than 6 weeks results in severe disability, and even open reduction with stabilization through wide dorsal and volar approaches is technically challenging. This report describes an arthroscopic technique for reduction and percutaneous wire stabilization of a chronic perilunate wrist dislocations. The technique involves initial radiocarpal and midcarpal access through the 6R and 3-4 portals, and these portals are used for synovectomy and debridement of capsular flap tears. The midcarpal joint is accessed initially through the radiocarpal joint, and additional midcarpal portals are used for sequential perilunate adhesiolysis before carpal mobilization and reduction. A percutaneous wire drilled into the lunate is used as a joystick to manipulate the lunate into its anatomic alignment along the carpal bones, and percutaneous transcarpal wire fixation is performed to stabilize the carpus. Arthroscopic and fluoroscopic guidance is used to optimize anatomic reduction and to confirm stability. The wrist is immobilized for 6 weeks; the percutaneous wires are removed thereafter, and the wrist is mobilized. Overall, the arthroscopic technique provides a safe and reproducible method for treatment of this complex chronic injury. PMID- 27354949 TI - Posterior Meniscal Root Repair: The Transtibial Double Tunnel Pullout Technique. AB - Meniscal root tears are increasingly recognized as an important pathology. Failure to recognize this pathology could lead to early onset osteoarthritis of the ipsilateral knee joint compartment similar to a total meniscectomy. Therefore, surgical treatment is necessary to restore meniscal function and to normalize contact pressures, when there is joint overload and sufficient remaining articular cartilage. This article details our anatomic posterior root repair procedure using a transtibial double tunnel pullout technique. PMID- 27354950 TI - A Technique of Improved Medial Meniscus Visualization by Anterior Cruciate Ligament Graft Placement in Chronic Anterior Cruciate Deficient Knees. AB - It is customary to perform medial meniscus repair before anterior cruciate ligament (ACL) graft placement when undertaken as a combined procedure. However, in chronic ACL-deficient knees, intraoperative anterior tibiofemoral translation can cause the medial meniscus repair to be more technically challenging. Intraoperative anterior tibiofemoral translation can both reduce the visualization of the medial meniscus and make its reduction unstable. An operative sequence alteration of ACL graft placement and tensioning before medial meniscal repair improves medial meniscus visualization in chronically ACL deficient knees by using the ACL graft's ability to prevent anterior tibiofemoral translation. The technique sequence is as follows: (a) the medial meniscus is reduced, (b) ACL reconstruction is undertaken using a hamstring graft without final tibia fixation, PMID- 27354951 TI - Anatomic Fibular Collateral Ligament Reconstruction. AB - Fibular collateral ligament (FCL) injuries can lead to varus instability of the knee, causing a varus thrust gait and resulting in increased forces on the medial compartment of the knee. In the long term, this can result in meniscal injuries and medial compartment osteoarthritis. Varus instability is also reported to increase forces on the cruciate ligaments, which can lead to overload and failure of these reconstructions in cases of nonrecognized combined injuries. Historically, both repair and reconstruction have been used for grade III injuries to the FCL. However, repair has been reported to lead to a higher reoperation rate. The hereby presented reconstruction technique is used for FCL injuries that do not involve other structures of the posterolateral corner, but can be used in combination with other knee ligament reconstructions including the posterior cruciate ligament, anterior cruciate ligament, and medial collateral ligament. The purpose of this surgical technique article was to describe the biomechanically validated anatomic reconstruction of the FCL using a semitendinosus graft. PMID- 27354952 TI - Arthroscopic Knotless Repair of the Posterior Labrum Using LabralTape. AB - Operative management of symptomatic labral tears of the shoulder has traditionally been the preferred treatment. Arthroscopic techniques and equipment continue to be refined and subsequent new recommendations for treatment are being developed. Contemporary techniques for arthroscopic knotless repair offer possible advantages over traditional arthroscopically tied knots. Although knotless repair of labral tears is well recognized, advancements continue to progress toward stronger fixation with reduced risks of cutting through the labrum and chondral abrasion. The suture tape used in the technique presented for arthroscopic knotless repair is stronger and flatter than traditional rounded suture and offers many potential benefits. PMID- 27354953 TI - Soft-Tissue Loop for Medial Patellofemoral Ligament Reconstruction. AB - A patient with patellar instability frequently presents with anterior knee pain, patellar subluxation, or dislocation. Medial patellofemoral ligament (MPFL) has a key role for normal patella tracking and stability. Reconstruction of the MPFL using a hamstring graft is a commonly used procedure for the treatment of chronic lateral subluxation of patella. Anchor sutures and bony tunnels are used for the patellar attachment of the graft. This can be associated with complications such as patella fracture; besides, it does not produce an anatomical reconstruction for the native MPFL that can alter the direction of tension applied on the patella. To overcome these problems, a soft-tissue loop technique is used for MPFL reconstruction. During this procedure, a semitendinosus graft was passed through the prepatellar extensor retinaculum and secured with sutures. The free ends of the graft were then passed between the second and third layers of the medial patellofemoral retinaculum and fixed to a femoral tunnel on the medial femoral condyle with an interference screw. The desired amount of tension on the graft is achieved under direct vision of patella tracking arthroscopically. We found this method to be relatively safe and fast. It is more anatomical and can avoid the complications during the conventional bony procedures. PMID- 27354954 TI - Hip Labral Reconstruction: The "Kite Technique" for Improved Efficiency and Graft Control. AB - Although the merits of labral reconstruction have been well established, the technical difficulty of presently used reconstruction techniques-particularly with graft passage and fixation-limit its efficacy and potentiates the risk of iatrogenic damage within the hip joint. The unwieldy nature of a floating labral graft anchored on one end may impede accurate fixation of the other end, which is critical for restoration of the fluid hip seal and preservation of graft integrity. In this technique narrative, we present a "kite technique" for introduction, control, and efficient fixation of a labral reconstruction graft. The principles of this method are founded on the belief that a soft-tissue graft in an arthroscopic environment is much easier to guide into position with 2 control sutures using a pulley system similar to flying a kite with 2 fly lines. Although we herein detail the technique as it applies to labral reconstruction in the hip, the concept of the kite technique may also be employed in arthroscopic assisted soft-tissue reconstructions of other joints. PMID- 27354955 TI - Lung histopathological pattern in a survivor with rapidly progressive interstitial lung disease and anti-melanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis. AB - Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are specific indicators of patients with dermatomyositis, particularly clinically amyopathic dermatomyositis (CADM). CADM is occasionally accompanied by fatal, treatment resistant, rapidly-progressive interstitial lung disease (RP-ILD). All previous reports showed that histopathological findings in RP-ILD with anti-MDA5 antibody positive CADM indicated diffuse alveolar damage (DAD). This is the first report describing a non-DAD pattern in RP-ILD with anti-MDA5 antibody-positive CADM, which was improved by immunosuppressive therapy. This case may be a milder clinical phenotype than a typical DAD pattern in RP-ILD with anti-MDA5 antibody positive CADM. PMID- 27354956 TI - Non-parametric intravoxel incoherent motion analysis in patients with intracranial lesions: Test-retest reliability and correlation with arterial spin labeling. AB - Intravoxel incoherent motion (IVIM) analysis of diffusion imaging data provides biomarkers of true passive water diffusion and perfusion properties. A new IVIM algorithm with variable adjustment of the b-value threshold separating diffusion and perfusion effects was applied for cerebral tissue characterization in healthy volunteers, computation of test-retest reliability, correlation with arterial spin labeling, and assessment of applicability in a small cohort of patients with malignant intracranial masses. The main results of this study are threefold: (i) accounting for regional differences in the separation of the perfusion and the diffusion components improves the reliability of the model parameters; (ii) if differences in the b-value threshold are not accounted for, a significant tissue dependent systematic bias of the IVIM parameters occurs; (iii) accounting for voxel-wise differences in the b-value threshold improves the correlation with CBF measurements in healthy volunteers and patients. The proposed algorithm provides a robust characterization of regional micro-vascularization and cellularity without a priori assumptions on tissue diffusion properties. The glioblastoma multiforme with its inherently high variability of tumor vascularization and tumor cell density may benefit from a non-invasive clinical characterization of diffusion and perfusion properties. PMID- 27354957 TI - Selective functional connectivity abnormality of the transition zone of the inferior parietal lobule in schizophrenia. AB - Structural and functional alterations in the inferior parietal lobule (IPL) in schizophrenia have been frequently reported; however, the IPL connectivity changes in schizophrenia remain largely unknown. Based on heterogeneity of the IPL in structure, connection and function, we hypothesize that the resting-state functional connectivities (rsFCs) of the IPL subregions are differentially affected in schizophrenia. This study included 95 schizophrenia patients and 104 healthy controls. The IPL subregions were defined according to a previous in vivo connection-based parcellation study. We calculated the rsFC of each IPL subregion and compared them between the two groups while controlling for the effects of age, gender, and grey matter volume. Among the six subregions of the left IPL and the five subregions of the right IPL, only the bilateral PFm (a transition zone of the IPL) subregions exhibited abnormal rsFC in schizophrenia. Specifically, the left PFm showed increased rsFC with the bilateral lingual gyri in schizophrenia patients than in healthy controls. The right PFm exhibited increased rsFC with the right lingual gyrus and inferior occipital gyrus, and bilateral mid-cingulate and sensorimotor cortices in schizophrenia patients. These findings suggest a selective rsFC abnormality in the IPL subregions in schizophrenia, characterized by the increased rsFC between the PFm subregion of the IPL and the visual and sensorimotor areas. PMID- 27354959 TI - Reporting and understanding the safety and adverse effect profile of mobile apps for psychosocial interventions: An update. AB - Recent years have seen a rapidly increasing trend towards the delivery of health technology through mobile devices. Smartphones and tablet devices are thus becoming increasingly popular for accessing information and a wide range of services, including health care services. Modern mobile apps can be used for a variety of reasons, ranging from education for the patients and assistance to clinicians to delivery of interventions. Mobile phone apps have also been established to benefit patients in a scope of interventions across numerous medical specialties and treatment modalities. Medical apps have their advantages and disadvantages. It is important that clinicians have access to knowledge to make decisions regarding the use of medical apps on the basis of risk-benefit ratio. Mobile apps that deliver psycho social interventions offer unique challenges and opportunities. A number of reviews have highlighted the potential use of such apps. There is a need to describe, report and study their side effects too. The adverse effects associated with these apps can broadly be divided into: (1) those resulting from the security and safety concerns; (2) those arising from the use of a particular psycho social intervention; and (3) those due to the interaction with digital technology. There is a need to refine and reconsider the safety and adverse effects in this area. The safety profile of a mobile PSI app should describe its safety profile in: (1) privacy and security; (2) adverse effects of psychotherapy; and (3) adverse effects unique to the use of apps and the internet. This is, however, a very new area and further research and reporting is required to inform clinical decision making. PMID- 27354958 TI - Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness. AB - BACKGROUND: Structural brain abnormalities in schizophrenia have been repeatedly demonstrated in magnetic resonance imaging (MRI) studies, but it remains unclear whether these are static or progressive in nature. While longitudinal MRI studies have been traditionally used to assess the issue of progression of brain abnormalities in schizophrenia, information from cross-sectional neuroimaging studies directly comparing first-episode and chronic schizophrenia patients to healthy controls may also be useful to further clarify this issue. With the recent interest in multisite mega-analyses combining structural MRI data from multiple centers aiming at increased statistical power, the present multisite voxel-based morphometry (VBM) study was carried out to examine patterns of brain structural changes according to the different stages of illness and to ascertain which (if any) of such structural abnormalities would be specifically correlated to potential clinical moderators, including cumulative exposure to antipsychotics, age of onset, illness duration and overall illness severity. METHODS: We gathered a large sample of schizophrenia patients (161, being 99 chronic and 62 first-episode) and controls (151) from four previous morphometric MRI studies (1.5 T) carried out in the same geographical region of Brazil. Image processing and analyses were conducted using Statistical Parametric Mapping (SPM8) software with the diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) algorithm. Group effects on regional gray matter (GM) volumes were investigated through whole-brain voxel-wise comparisons using General Linear Model Analysis of Co-variance (ANCOVA), always including total GM volume, scan protocol, age and gender as nuisance variables. Finally, correlation analyses were performed between the aforementioned clinical moderators and regional and global brain volumes. RESULTS: First-episode schizophrenia subjects displayed subtle volumetric deficits relative to controls in a circumscribed brain regional network identified only in small volume corrected (SVC) analyses (p < 0.05, FWE-corrected), including the insula, temporolimbic structures and striatum. Chronic schizophrenia patients, on the other hand, demonstrated an extensive pattern of regional GM volume decreases relative to controls, involving bilateral superior, inferior and orbital frontal cortices, right middle frontal cortex, bilateral anterior cingulate cortices, bilateral insulae and right superior and middle temporal cortices (p < 0.05, FWE corrected over the whole brain). GM volumes in several of those brain regions were directly correlated with age of disease onset on SVC analyses for conjoined (first-episode and chronic) schizophrenia groups. There were also widespread foci of significant negative correlation between duration of illness and relative GM volumes, but such findings remained significant only for the right dorsolateral prefrontal cortex after accounting for the influence of age of disease onset. Finally, significant negative correlations were detected between life-time cumulative exposure to antipsychotics and total GM and white matter volumes in schizophrenia patients, but no significant relationship was found between indices of antipsychotic usage and relative GM volume in any specific brain region. CONCLUSION: The above data indicate that brain changes associated with the diagnosis of schizophrenia are more widespread in chronic schizophrenia compared to first-episode patients. Our findings also suggest that relative GM volume deficits may be greater in (presumably more severe) cases with earlier age of onset, as well as varying as a function of illness duration in specific frontal brain regions. Finally, our results highlight the potentially complex effects of the continued use of antipsychotic drugs on structural brain abnormalities in schizophrenia, as we found that cumulative doses of antipsychotics affected brain volumes globally rather than selectively on frontal-temporal regions. PMID- 27354960 TI - Bilingualism and schizophrenia. AB - Although a bilingual advantage has been described for neurodegenerative disease in general, it is not known whether such an advantage could accrue to individuals suffering from schizophrenia, since language networks are known to be disrupted in this condition. The aim of this minireview was to scan the existing literature to determine: (1) whether individuals with schizophrenia are able to learn a second language as adults; (2) whether clinical assessment, both for the purpose of accurate diagnosis and for the prediction of treatment response, should be carried out in both languages in bilinguals with schizophrenia; (3) whether psychotherapy in schizophrenia is affected by bilingualism; and (4) whether speaking a second language improves outcome in schizophrenia. The literature to date is too sparse to make definitive statements, but: (1) individuals with schizophrenia appear to be capable of learning a new languages as adults; and (2) it is possible that teaching a foreign language may serve as a form of cognitive rehabilitation for this condition. This literature review recommends research into the effects of bilingualism on the outcome of schizophrenia. Included in this review is a retrospective pilot study conducted in Canada, which suggests that employment opportunities for patients with schizophrenia are improved when they speak more than one language. This is important to note because employment is generally problematic in the context of schizophrenia while, at the same time, the ability to obtain work contributes significantly to quality of life. PMID- 27354961 TI - Vascular cognitive impairment, a cardiovascular complication. AB - Over the past two decades, the term vascular cognitive impairment (VCI) has been used to refer to a spectrum of cognitive decline characterized by executive dysfunction, associated with vascular pathology. With 30% of stroke survivors showing cognitive impairments, it is regarded as the most common cause of cognitive impairment. This is a narrative review of available literature citing sources from PubMed, MEDLINE and Google Scholar. VCI has a high prevalence both before and after a stroke and is associated with great economic and caregiver burden. Despite this, there is no standardized diagnostic criteria for VCI. Hypertension has been identified as a risk factor for VCI and causes changes in cerebral vessel structure and function predisposing to lacuna infarcts and small vessel haemorrhages in the frontostriatal loop leading to executive dysfunction and other cognitive impairments. Current trials have shown promising results in the use of antihypertensive medications in the management of VCI and prevention of disease progression to vascular dementia. Prevention of VCI is necessary in light of the looming dementia pandemic. All patients with cardiovascular risk factors would therefore benefit from cognitive screening with screening instruments sensitive to executive dysfunction as well as prompt and adequate control of hypertension. PMID- 27354962 TI - Linking multiple pathogenic pathways in Alzheimer's disease. AB - Alzheimer's disease (AD) is a chronic neurodegenerative disorder presenting as progressive cognitive decline with dementia that does not, to this day, benefit from any disease-modifying drug. Multiple etiologic pathways have been explored and demonstrate promising solutions. For example, iron ion chelators, such as deferoxamine, are a potential therapeutic solution around which future studies are being directed. Another promising domain is related to thrombin inhibitors. In this minireview, a common pathophysiological pathway is suggested for the pathogenesis of AD to prove that all these mechanisms converge onto the same cascade of neuroinflammatory events. This common pathway is initiated by the presence of vascular risk factors that induce brain tissue hypoxia, which leads to endothelial cell activation. However, the ensuing hypoxia stimulates the production and release of reactive oxygen species and pro-inflammatory proteins. Furthermore, the endothelial activation may become excessive and dysfunctional in predisposed individuals, leading to thrombin activation and iron ion decompartmentalization. The oxidative stress that results from these modifications in the neurovascular unit will eventually lead to neuronal and glial cell death, ultimately leading to the development of AD. Hence, future research in this field should focus on conducting trials with combinations of potentially efficient treatments, such as the combination of intranasal deferoxamine and direct thrombin inhibitors. PMID- 27354963 TI - Failure of memantine to "reverse" quinpirole-induced hypomotility. AB - AIM: To evaluate antidepressant-like effect of memantine in a rat model. METHODS: Male Wistar rats were treated intraperitoneally with either vehicle, memantine (10 mg/kg) or imipramine (20 mg/kg), for 3 wk. Twenty-four hour after the last treatment animals were challenged with quinpirole (0.3 mg/kg s.c.) and tested for motor activity. After 1 h habituation to the motility cages, the motor response was recorded for the following 45-min and the data were collected in 5-min time bins. RESULTS: As expected, chronic treatment with imipramine potentiated the locomotor stimulant effect of quinpirole. On the contrary, chronic memantine administration failed to induce the behavioral supersensitivity to the dopamine agonist. CONCLUSION: The results show that memantine, at variance with antidepressant treatments, fails to induce dopaminergic behavioral supersensitivity. This observation is consistent with the results of preclinical and clinical studies suggesting that memantine does not have an acute antidepressant action but does have an antimanic and mood-stabilizing effect. PMID- 27354964 TI - Hippocampus and amygdala volumes in patients with vaginismus. AB - AIM: To compare hippocampus and amygdala volumes of patients with vaginismus with those of healthy control subjects. METHODS: Magnetic resonance imaging was performed on ten patients with vaginismus and ten control subjects matched for age and gender. Volumes of the hippocampus and amygdala were blindly measured. RESULTS: We found that the mean right amygdala volume of patients with vaginismus were smaller than that of the healthy controls. With regard to hippocampus volumes, the mean left and right hippocampus volumes were smaller than those of the healthy controls. CONCLUSION: Our present findings suggest that there have been hippocampus and amygdala structural abnormalities in patients with vaginismus. These changes provide the notion that vaginismus may be a fear related condition. PMID- 27354965 TI - Peritraumatic Behavior Questionnaire - Observer Rated: Validation of the objective version of a measure for combat-related peritraumatic stress. AB - AIM: To validate the first third-person-rated measure assessing combat-related peritraumatic stress symptoms and evaluate its psychometric properties and war zone applicability. METHODS: The valid assessment of peritraumatic symptoms in the theater of military operations represents a significant challenge in combat related, mental health research, which mainly relies on retrospective, subjective self-report ratings. This longitudinal observational study used data from actively deployed troops to correlate third-person observer ratings of deployment peritraumatic behaviors [Peritraumatic Behavior Questionnaire - Observer Rated (PBQ-OR)] collected on a bi-monthly basis with post-deployment (1-wk follow-up) ratings of the previously validated PBQ self-rate version (PBQ-SR), and (3-mo follow-up) clinician assessed and self-report posttraumatic stress disorder (PTSD) symptoms (Clinician Administered PTSD Scale, PTSD Checklist). Cronbach's alpha (alpha) and correlation coefficients were calculated to assess internal reliability and concurrent validity respectively. RESULTS: Eight hundred and sixty male Marines were included in this study after signing informed consents at pre-deployment (mean age 23.2 +/- 2.6 years). Although our findings were limited by an overall sparse return rate of PBQ-OR ratings, the main results indicate satisfactory psychometric properties with good internal consistency for the PBQ OR (alpha = 0.88) and high convergent and concurrent validity with 1-wk post deployment PBQ-SR ratings and 3-mo posttraumatic stress symptoms. Overall, later PBQ-OR report date was associated with higher correlation between PBQ-OR and post deployment measures. Kappa analysis between PBQ-OR and PBQ-SR single items, showed best agreement in questions relating of mortal peril, desire for revenge, and experience of intense physical reactions. Logistic regression demonstrated satisfactory predictive validity of PBQ-OR total score with respect to PTSD caseness (OR = 1.0513; 95%CI: 1.011-1.093; P = 0.02). CONCLUSION: Since no comparable tools have been developed, PBQ-OR could be valuable as real-time screening tool for earlier detection of Service Members at risk. PMID- 27354966 TI - Association between recognizing dementia as a mental illness and dementia knowledge among elderly Chinese Americans. AB - AIM: To investigate whether older Chinese Americans perceive dementia as a mental illness and the relationship between such perception and their general understanding of dementia remains unclear. Our study aims to understand this relationship and its future implication on improving dementia literacy among ethnic minorities. METHODS: Elderly Chinese American participants from the Greater Los Angeles were asked to complete an 11-item dementia questionnaire, following a community health seminar. Cross-sectional survey data was analyzed using standard statistical methods. RESULTS: The questionnaire received an 88.3% response rate. Among 316 responders, only 28.8% (n = 91) of elderly Chinese Americans identified dementia as a mental illness, and 71.2% (n = 225) did not recognize its mental disease origin. Furthermore, in comparison between these two groups, the first group demonstrated significantly higher level of baseline knowledge of the disease. CONCLUSION: This study reveals that only approximately 1 out of 4 older Chinese Americans recognized dementia as a mental illness, consistent with previous studies on Asian Americans. Our study however showed that when dementia was being perceived as a mental illness, such perception was associated with a higher level of baseline dementia understanding. The current study suggested the potential of improving older Chinese Americans dementia literacy by increasing awareness of its mental illness origin. PMID- 27354967 TI - Effectiveness of an intervention for reducing social stigma towards mental illness in adolescents. AB - AIM: To evaluate the effectiveness of an intervention for reducing social stigma towards mental illness in adolescents. The effect of gender and knowledge of someone with mental illness was measured. METHODS: Two hundred and eighty secondary school students were evaluated using the Community Attitudes towards Mental Illness (CAMI) questionnaire. The schools were randomized and some received the intervention and others acted as the control group. The programme consisted of providing information via a documentary film and of contact with healthcare staff in order to reduce the social stigma within the school environment. RESULTS: The intervention was effective in reducing the CAMI authoritarianism and social restrictiveness subscales. The intervention showed significant changes in girls in terms of authoritarianism and social restrictiveness, while boys only showed significant changes in authoritarianism. Following the intervention, a significant reduction was found in authoritarianism and social restrictiveness in those who knew someone with mental illness, and only in authoritarianism in those who did not know anyone with mental illness. CONCLUSION: The intervention was effective to reduce social stigma towards people with mental illness, especially in the area of authoritarianism. Some differences were found depending on gender and whether or not the subjects knew someone with mental illness. PMID- 27354968 TI - Path analysis of relationship among personality, perceived stress, coping, social support, and psychological outcomes. AB - AIM: To provide a structural model of the relationship between personality traits, perceived stress, coping strategies, social support, and psychological outcomes in the general population. METHODS: This is a cross sectional study in which the study group was selected using multistage cluster and convenience sampling among a population of 4 million. For data collection, a total of 4763 individuals were asked to complete a questionnaire on demographics, personality traits, life events, coping with stress, social support, and psychological outcomes such as anxiety and depression. To evaluate the comprehensive relationship between the variables, a path model was fitted. RESULTS: The standard electronic modules showed that personality traits and perceived stress are important determinants of psychological outcomes. Social support and coping strategies were demonstrated to reduce the increasing cumulative positive effects of neuroticism and perceived stress on the psychological outcomes and enhance the protective effect of extraversion through decreasing the positive effect of perceived stress on the psychological outcomes. CONCLUSION: Personal resources play an important role in reduction and prevention of anxiety and depression. In order to improve the psychological health, it is necessary to train and reinforce the adaptive coping strategies and social support, and thus, to moderate negative personality traits. PMID- 27354969 TI - Facial emotion perception in schizophrenia: Does sex matter? AB - AIM: To review the literature on sex differences in facial emotion perception (FEP) across the schizophrenia spectrum. METHODS: We conducted a systematic review of empirical articles that were included in five separate meta-analyses of FEP across the schizophrenia spectrum, including meta-analyses that predominantly examined adults with chronic schizophrenia, people with early (onset prior to age 18) or recent-onset (experiencing their first or second psychotic episode or illness duration less than 2 years) schizophrenia, and unaffected first-degree relatives of people with schizophrenia. We also examined articles written in English (from November 2011 through June 2015) that were not included in the aforementioned meta-analyses through a literature search in the PubMed database. All relevant articles were accessed in full text. We examined all studies to determine the sample sizes, diagnostic characteristics, demographic information, methodologies, results, and whether each individual study reported on sex differences. The results from the meta-analyses themselves as well as the individual studies are reported in tables and text. RESULTS: We retrieved 134 articles included in five separate meta-analyses and the PubMed database that examined FEP across the schizophrenia spectrum. Of these articles, 38 examined sex differences in FEP. Thirty of these studies did not find sex differences in FEP in either chronically ill adults with schizophrenia, early-onset or recently diagnosed people with schizophrenia, or first-degree relatives of people with schizophrenia. Of the eight studies that found sex differences in FEP, three found that chronically ill women outperformed men, one study found that girls with early-onset schizophrenia outperformed boys, and two studies found that women (including first-degree relatives, adults with schizophrenia, and the healthy control group) outperformed men on FEP tasks. In total, six of the eight studies that examined sex differences in FEP found that women outperformed men across the schizophrenia spectrum. CONCLUSION: Evidence to date suggests few sex differences in FEP in schizophrenia; both men and women across the schizophrenia spectrum have deficits in FEP. PMID- 27354971 TI - Urinary capillariosis in six dogs from Italy. AB - Canine urinary capillariosis is caused by the nematode Pearsonema plica. P. plica infection is seldomly detected in clinical practice mainly due to diagnostic limitations. This report describes six cases of urinary capillariosis in dogs from Italy. Recurrent cystitis was observed in one dog, whereas another patient was affected by glomerular amyloidosis. In the remaining animals, the infection was considered an incidental finding. Immature eggs of the parasite were observed with urine sediment examination in 3/6 patients. Increased awareness of the potential pathogenic role of P. plica and clinical disease presentation could help identify infected animals. PMID- 27354970 TI - Review of key telepsychiatry outcomes. AB - AIM: To conduct a review of the telepsychiatry literature. METHODS: We conducted a systematic search of the literature on telepsychiatry using the search terms, "telepsychiatry", "telemental health", "telecare", "telemedicine", "e-health", and "videoconferencing". To meet criteria for inclusion, studies had to: (1) be published in a peer-reviewed journal after the year 2000; (2) be written in English; (3) use videoconferencing technology for the provision of mental health assessment or treatment services; and (4) use an adequately-powered randomized controlled trial design in the case of treatment outcome studies. Out of 1976 studies identified by searches in PubMed (Medline database), Ovid medline, PsychInfo, Embase, and EBSCO PSYCH, 452 met inclusion criteria. Studies that met all inclusion criteria were organized into one of six categories: (1) satisfaction; (2) reliability; (3) treatment outcomes; (4) implementation outcomes; (5) cost effectiveness; and (6) and legal issues. All disagreements were resolved by reassessing study characteristics and discussion. RESULTS: Overall, patients and providers are generally satisfied with telepsychiatry services. Providers, however, tend to express more concerns about the potentially adverse of effects of telepsychiatry on therapeutic rapport. Patients are less likely to endorse such concerns about impaired rapport with their provider. Although few studies appropriately employ non-inferiority designs, the evidence taken together suggests that telepsychiatry is comparable to face-to-face services in terms of reliability of clinical assessments and treatment outcomes. When non-inferiority designs were appropriately used, telepsychiatry performed as well as, if not better than face-to-face delivery of mental health services. Studies using both rudimentary and more sophisticated methods for evaluating cost effectiveness indicate that telepsychiatry is not more expensive than face-to face delivery of mental health services and that telepsychiatry is actually more cost-effective in the majority of studies reviewed. Notwithstanding legal concerns about loss of confidentiality and limited capacity to respond to psychiatric emergencies, we uncovered no published reports of these adverse events in the use of telepsychiatry. CONCLUSION: A large evidence base supports telepsychiatry as a delivery method for mental health services. Future studies will inform optimal approaches to implementing and sustaining telepsychiatry services. PMID- 27354972 TI - Association of circulating irisin levels with normal weight obesity, glycemic and lipid profile. AB - BACKGROUND: Irisin, a recently identified myokine/adipokine, has potential role in type 2 diabetes and obesity. Normal weight obesity (NWO) is associated with a significantly higher risk of developing metabolic syndrome and cardiometabolic dysfunction. The aim of this study was to investigate association of irisin level with NWO, glycemicand lipid profile in women. METHODS: In this matchedcase control study, 38 subjects with NWO (body mass index (BMI) <25 kg/m2 and BF % > 30) as case and 26 controls (BMI <25 kg/m2 and BF % < 30) were selected randomly from sport clubs in the East area of Tehran, Iran. In addition to anthropometric variables, including BMI and body composition, fasting blood sugar (FBS), fasting levels of irisin andinsulin, triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol were measured. All statistical analyses were performed with SPSS 18.0. RESULTS: In univariate analysis, levels of irisin were significantly higher in subjects with NWO compared to controls (0.81 +/- 0.41vs. 0.58 +/- 0.26 ng/ml, P = 0.009). This association remained significant after adjusting for confounders (adjusted for energy intake, physical activity, waist circumference and BMI) (P = 0.049). In NWO, irisin level was not significantly correlated with all glycemic and lipid profile. In control group, only correlation ofirisin with insulin was statistically significant (P = 0.03). CONCLUSION: Serum irisin levels were higher in NWO subjects than controls. In control group, only the negative association between irisin and insulin levels was statistically significant. Further studies with larger sample size are clearly needed to evaluate the potential role of irisin in NWO subject and other disturbed metabolic conditions. PMID- 27354973 TI - The Level of Professionalism of Nurses Working in a Hospital in Turkey. AB - INTRODUCTION: Professionalism is characterized by the degree of dedication displayed by individuals regarding the values and behavioral attributes of a specific career identity. Professionalism indicates attitudes that represent high levels of identification with and commitment to a specific profession. In the process of the professional development of nursing, various factors affect these obstacles which may impede the professional development of nurses and their professional behaviors. This study was carried out with the aim of determining the professional behavior of nurses in a hospital in Turkey. METHODS: In this descriptive exploratory study a total of 89 nurses working in a public hospital in northwestern of Turkey were participated. Data were collected using a demographic questionnaire and Behavioral Inventory Form for Professionalism in Nursing (BIPN). RESULTS: The result showed that mean scores on the BIPN were 5.07 (3.47). The areas with the highest levels of professional behavior were competence and continuing education 1.88 (0.34). The professionalism levels for nurses were the lowest in the areas of autonomy 0.06 (0.34), publication 0.10 (0.25), and research 0.25 (0.60). There was a statistically significant difference between the total BIPN scores and the education levels of the nurses and the working of nurses. CONCLUSION: The professional behavior of nurses is at a low level. Since the arrangement of the nurses' working conditions affects their professional behaviors; therefore, development in the field of professional behaviors in nursing must be assessed and supported to increase the quality of patient care. PMID- 27354974 TI - Effect of White Noise on Sleep in Patients Admitted to a Coronary Care. AB - INTRODUCTION: Sleep disorders are a common problem in patients in the critical care unit. The objective of the present study was to determine the effect of white noise on the quality of sleep in patients admitted to the CCU. METHODS: The present study was single-blind, quasi-experimental study. A total of 60 patients were selected using the purposive sampling method. Quality of sleep was measured with PSQI on the first day in admission, then after three nights of admission without any intervention for control group and for the experimental group quality of sleep measured by white noise with intensity of 50-60 dB then Quality of sleep was measured with PSQI. Data were analyzed by SPSS 13 software. RESULTS: The average total sleep time in the control group before the study reached from 7.08 (0.8) to 4.75 (0.66) hours after three nights of hospitalization, while in the experimental group, no significant changes were seen in the average sleep hours (6.69 +/- 0.84 vs. 6.92 +/- 0.89, P = 0.15).The average minutes of sleep in the control group before the study reached from 12.66 (7.51) to 25.83 (11.75) minutes after a three- night stay, while in the experimental group, no significant changes were observed in the average sleep duration (12.16 +/- 7.50 vs. 11 +/-6. 07, P = 0.16). CONCLUSION: The use of white noise is recommended as a method for masking environmental noises, improving sleep, and maintaining sleep in the coronary care unit. PMID- 27354975 TI - The impact of Multimedia Software Support on the Knowledge and Self-Care Behaviors of Patients with Type 2 Diabetes: a Randomized Clinical Trial. AB - INTRODUCTION: Education is the most effective and economical part of diabetes treatment. The purpose of this study was to investigate the effect of a training program with multimedia software on the knowledge and self-care behaviors of patients with type 2 diabetes. METHODS: This study was a randomized controlled clinical trial in which 60 patients referred to diabetes clinic at Arak city were divided randomly into experimental (n=30) and control (n=30) groups. The instruments for collecting data were "Summary of Diabetes self-care activities questionnaire" and "knowledge of self-care in patients with diabetes". Data were collected before and 2 months after the intervention in the both groups. Educational program with equal content was applied for both experimental group (self-care program with multimedia software support) & control group (lecture and presentation with PowerPoint). Data analysis was done using SPSS Ver.13. RESULTS: Implementation of the self-care program with multimedia software support resulted in improvements in patients' self-care behaviors in the experimental group, whereas these behaviors had not significant changes in the control group after eight weeks. There was a significant difference in the mean score of knowledge in both the experiment and control groups before and after the intervention. CONCLUSION: Considering beneficial effects of training program with multimedia software support on the knowledge and self-care behaviors and the importance of this issue, suggested that the patients preferably provide terms of use of educational software for themselves. PMID- 27354976 TI - Is Nurses' Professional Competence Related to Their Personality and Emotional Intelligence? A Cross-Sectional Study. AB - INTRODUCTION: Nurses' professional competence is a crucial factor in clinical practice. Systematic evaluation of nurses' competence and its related factors are essential for enhancing the quality of nursing care. This study aimed to assess the nurses' competence level and its possible relationship with their personality and emotional intelligence. METHODS: Using a cross-sectional survey design, three instruments including Nurse Competence Scale, short form of Schutte Self Report Emotional Intelligence Test, and the short 10-item version of Big Five Factor Inventory, were administered simultaneously to a randomized stratified sample of 220 nurses working in hospitals affiliated to Mashhad University of Medical Sciences. Data analysis was performed using SPSS 11.5. RESULTS: Majority of nurses rated themselves as "good" and "very good", with the highest scores in "managing situations" and "work role" dimensions of nurse competence. A relatively similar pattern of scores was seen in competence dimensions, personality and emotional intelligence, among male and female nurses. Emotional intelligence and personality scores showed a significant relationship with nurses' competence, explaining almost 20% of variations in nurse competence scores. CONCLUSION: Iranian nurses evaluated their overall professional competence at similar level of the nurses in other countries. Knowledge about the nurses' competence level and its related factors, including personality and emotional intelligence, may help nurse managers in enhancing nurses' professional competence through appropriate task assignments and conducting in-service educational programs, thus improving the health status of patients. PMID- 27354977 TI - "Where Withstanding is Difficult, and Deserting Even More": Head Nurses' Phenomenological Description of Intensive Care Units. AB - INTRODUCTION: The intensive care unit is one of the specialized units in hospitals where head nurses are responsible for both motivating the personnel and providing high quality care. Understanding of the lived experiences of head nurses could help develop new assumptions of the ICU. The present study was therefore conducted to describe the lived experiences of head nurses working in ICU. METHODS: In this phenomenological study, data were collected through unstructured in-depth interviews with 5 ICU head nurses in Northern Iran and then analyzed using 7 steps Colaizzi's method. RESULTS: Despite the "distressing atmosphere of the ICU", the "difficulty of managing the ICU" and the "difficulty of communication in the ICU", which encourages the "desire to leave the unit" among ICU head nurses, the "desire to stay in the unit" is stronger and head nurses are highly motivated to stay in the unit because the unit "develops a feeling of being extraordinary", "creates an interest in providing complicated care to special patients", "facilitates the spiritual bond", "develops a professional dynamism" and "creates an awareness about the nature of intensive care" among them. CONCLUSION: According to the result, ICU head nurses are still inclined to work in the unit and achieve success in spite of the problems that persist in working in the ICU. As the individuals' motivation can be the backbone of organizations, and given that individuals with a high enthusiasm for success are productive, hospital managers can take advantage of this strength in choosing their head nurses. PMID- 27354978 TI - Development and Preliminary Validation of Diabetes Adjustment Assessment Scale (DAAS): a New Measure of Adjustment with Type 2 Diabetes. AB - INTRODUCTION: Several adjustment scales are available for Diabetes, but, unfortunately most of them focused on the limited dimensions of diabetes and are not specific for type 2 diabetes. The aim of this study was to develop a multidimensional scale for Diabetes type 2 Adjustment Assessment and to test preliminary validity, reliability and clinical utility of the scale for this population. METHODS: In this methodological design study, the Diabetes Adjustment Assessment Scale was developed and the psychometric properties of this scale was assessed in patients with Type 2 diabetes. This study included internal consistency, content validity and exploratory factor analysis. RESULTS: 1000 patients with type 2 diabetes completed the 45-item Diabetes Adjustment Scale. After eliminating two item, the 43-item measure demonstrated good internal consistency (Cronbach's alpha= 0.75). Factor analysis identified eight factors including; reshape (11 questions), seek to acceptance of illness (7 questions), normal life with the disease (6 questions), initial self-management (2 questions), comparing (4 questions), initial imaging of illness (4 questions), return to resources(3 questions), and advanced self- management (6 questions). CONCLUSION: Considering that validity and reliability indexes of the scale are reported in an appropriate level, it can be used as a valid and reliable tool in measuring level of adjustment with type2 diabetes. PMID- 27354979 TI - Sleep Hygiene Practices and Their Relation to Sleep Quality in Medical Students of Qazvin University of Medical Sciences. AB - INTRODUCTION: Poor quality of sleep is a distressing and worrying condition that can disturb academic performance of medical students. Sleep hygiene practices are one of the important variables that affect sleep quality. The objective of this study was to assess association between sleep hygiene practices and sleep quality of medical students in Qazvin University of Medical Sciences. METHODS: In this descriptive-correlational study, a total of 285 medical students completed a self administered questionnaire. Demographic data, sleep-wake schedule in weekday and weekend, and sleep duration were collected. Students' sleep quality was assessed by Pittsburg Sleep Quality Index (PSQI). Data were analyzed by SPSS Ver 13. RESULTS: Overall, 164 (57.5) of students had poor sleep quality. Mean global PSQI score and average score of four subscales were significantly higher in male than female. Regression analysis showed that male students (beta=-0.85, P<0.05), students at senior level (beta=-0.81, P<0.05), married students (beta=-0.45, P<0.05), and those with improper sleep hygiene practices slept worse. CONCLUSION: The findings of this study showed that the prevalence of poor sleep quality in medical students is high. Improper sleep hygiene behaviors might be a reason for poor quality of sleep in medical students. PMID- 27354980 TI - The Effect of a Designed Respiratory Care Program on the Incidence of Ventilator Associated Pneumonia: A Clinical Trial. AB - INTRODUCTION: Ventilator-associated pneumonia is a common complication of mechanical ventilation. This study aimed to evaluate the effect of designed respiratory care program on incidence of ventilator-associated pneumonia (VAP) in the mechanically ventilated patient. METHODS: In this clinical trial, 64 patients were selected among those who had undergone mechanical ventilation in the ICU of Al-Zahra Hospital, Isfahan, Iran, using convenience sampling method. The subjects were randomly allocated to intervention and control groups. In the intervention group an upper respiratory care program and in the control group, routine cares were done. Modified Clinical Pulmonary Infection Questionnaire was completed before and on the third, fourth and fifth day of study. Data were analyzed by Chi square and independent t-test through SPSS Ver.13. RESULTS: The results of this study showed that until the third day of study, the incidence of VAP was similar in the both groups. However, on the fifth day of study, the incidence of VAP in the intervention group was significantly lower than control group. CONCLUSION: The results of this study showed that an upper respiratory care program reduced the incidence of VAP. Therefore, nurses are recommended to perform this program for prevention of VAP. PMID- 27354981 TI - Experiences of Iranian Nurses that Intent to Leave the Clinical Nursing: a Content Analysis. AB - INTRODUCTION: Despite the current shortage of nurses, it is important to know the reasons nurses want to leave the clinical setting. The purpose of this study was to explore the experiences of nurses who intend to leave clinical nursing. METHODS: In a qualitative content analysis study, data obtained from 13 in-depth face-to-face semi-structured interviews with nurses working in hospitals affiliated to the Tabriz and Urmia University of Medical Sciences in Iran, selected through purposive sampling. A conventional content analysis was used for data analysis. RESULTS: Four categories and eleven subcategories emerged during data analysis. The extracted categories and sub categories consisted of (I) Entry routes into nursing (implicitly entry, targeted entry), (II) Defects in dignity (lack of professional vision toward the nurses, social status of nurses), (III) Work in non-ideal working environment (lack of support, discrimination, conflict, lack of opportunities for advancement), and (IV) Dissatisfaction with working conditions (heavy workload, lack of power, unusual working hours). CONCLUSION: The findings of this qualitative study reflect professional turnover as a complex, ongoing, multidimensional process. By identifying the factors responsible, it could be possible to retain nurses in the field. PMID- 27354982 TI - Lacrimal Gland Intra-Lobular Duct Cysts Associated with Focal Vasculitis. AB - PURPOSE: Description of the clinical and histopathological features of unusual lacrimal gland intra-glandular duct cysts. PROCEDURES: A 38-year-old male presented with bilateral upper lid lumpiness, which was worse on the left. Computed tomography scan showed bilateral multiple lacrimal gland cysts, which were larger on the left compared to the right. After two unsuccessful attempts to excise the largest cyst on the left side, it was removed at the third attempt using a novel technique that incorporated the use of fibrin glue to fill the remaining cavity. RESULTS: The microscopy of the left-sided cyst comprised a cavity containing fibrin glue, lined by intra-lobular lacrimal gland duct epithelium. The cyst wall contained reactive lymphoid aggregates, plasma cells and eosinophils associated with fibrosis. Focally, there were small vessels affected by an acute vasculitis associated with eosinophils and a granulomatous component. CONCLUSIONS: We ascribe the cyst formation to the effects of tractional fibrosis secondary to focal vasculitis and to obstructive fibrosis of the lacrimal ductules. This case also described a novel use of Tisseel fibrin glue to assist intact removal of a lacrimal gland cyst. PMID- 27354983 TI - Progression of Cutaneous Vitiligo in a Patient with Large Posterior Choroidal Melanoma: A Case Report. AB - BACKGROUND/AIMS: The aim of our study was to report a case of progression of cutaneous vitiligo after large posterior choroidal melanoma diagnosis. METHODS: The clinical history, fundus findings and histopathological features suggest the diagnosis of cutaneous vitiligous progression after a diagnosis of large posterior choroidal melanoma. RESULTS: A 30-year-old female, with a personal history of cutaneous vitiligo for 12 years, was diagnosed with choroidal melanoma 18 months previously. The cutaneous vitiligo had progressed over her back, body and arms during the preceding 3 years. She refused treatment because she was in her 28th week of pregnancy. When she came to our clinic her visual symptoms had worsened, and the fundus examination showed a melanocytic choroidal mass. After confirming that there was no extraocular extension, she was treated with enucleation. A histopathological study confirmed the choroidal melanoma diagnosis. CONCLUSION: The association between the progression of vitiligo and the diagnosis of uveal melanoma could be considered a good prognostic factor, as has been described in cases of cutaneous melanoma. A longer follow-up of these patients will allow us to confirm this association. PMID- 27354984 TI - Diagnosing Pathological Prognostic Factors in Retinoblastoma: Correlation between Traditional Microscopy and Digital Slides. AB - OBJECTIVE: It was the aim of this study to determine the diagnostic accuracy of high-risk prognostic factors and morphological characteristics of retinoblastomas using digital whole slide images (WSI) generated by a scanner. METHODS: Forty seven H&E sections of glass slides with high-risk morphological features of retinoblastoma were analyzed. Slides were scanned as WSI and reviewed. The results were compared with those obtained after reviewing the slides using a regular microscope as the gold standard. McNemar's test (MT), the percentage of agreement (POA), and sensitivity (S) and specificity (Sp) were evaluated between WSI and conventional microscopy. RESULTS: There were no differences with respect to multicentricity, growth type, rosette formation, choroidal invasion, anterior chamber invasion, extraocular extension, scleral extension, optic nerve invasion, necrosis, or Azzopardi effect between WSI analysis and light microscopy (MT, p = 1.0; POA = 100%; S = 100%, and Sp = 100%). Discordance was found in 1 case where calcification could not be found using WSI (MT, p = 1.00; POA = 97.9%; S = 100%, and Sp = 97.8%). CONCLUSION: To the best of our knowledge, this is the first report using digital pathology (WSI) to evaluate prognostic factors in eyes containing retinoblastomas. Using WSI, the pathologist was able to detect high risk morphological features in retinoblastoma. To date, WSI is an important tool, in particular for ophthalmic pathologists examining enucleation and exenteration specimens. PMID- 27354985 TI - LGI1 antibody encephalopathy overlapping with sporadic Creutzfeldt-Jakob disease. AB - OBJECTIVE: To report a rare case of leucine-rich, glioma inactivated 1 (LGI1) antibody-mediated autoimmune encephalopathy clinically overlapping with pathologically confirmed sporadic Creutzfeldt-Jakob disease (CJD). METHODS: The patient was investigated with repeated brain MRI, EEG, CSF examination, whole body fluorodeoxy-glucose positron emission tomography, genetic analysis of the prion protein gene (PRNP), and extensive serologic screening for paraneoplastic and autoimmune encephalopathy markers. Written informed consent was obtained from the patient's next of kin for access to clinical files for research purposes and for publication. RESULTS: The patient was a 77-year-old man who presented with faciobrachial dystonic seizures (FBDS) secondary to LGI1 antibody-mediated autoimmune encephalopathy, with suggestive MRI findings and a complete response to treatment with combinatorial immunosuppression. Stereotactic biopsy of a nonenhancing T1 hyperintense basal ganglia lesion during the initial FBDS phase, albeit following immunosuppression, did not disclose evidence of lymphocytic inflammation. Following full remission of the FBDS, the patient manifested a rapidly progressive dementia associated with gross motor decline confirmed to be CJD at autopsy (molecular subtype VV3), with no evidence of a pathogenic PRNP mutation. CONCLUSIONS: Our patient highlights that these rare diseases are not invariably mutually exclusive and underscores the benefits of comprehensive neuropathologic examination of the brain to achieve an accurate diagnosis, especially in complex cases when the clinical trajectory dramatically deviates and a concomitant disease may need to be conscientiously considered to best explain the new clinical course. PMID- 27354986 TI - Monozygotic twins discordant for narcolepsy type 1 and multiple sclerosis. PMID- 27354987 TI - Delayed diagnosis of extraovarian teratoma in relapsing anti-NMDA receptor encephalitis. PMID- 27354988 TI - Aquaporin-4 IgG autoimmune syndrome and immunoreactivity associated with thyroid cancer. PMID- 27354989 TI - Aspirin and endometrial cancer risk. PMID- 27354990 TI - Tumor grade and chemotherapy response in endometrioid endometrial cancer. AB - The objective of this study is to evaluate the association between tumor grade and response to chemotherapy in patients with endometrioid endometrial adenocarcinoma. Patients with advanced or recurrent endometrioid endometrial adenocarcinoma of known tumor grade who received at least 3 cycles of chemotherapy were retrospectively identified at three institutions. RECIST 1.1 criteria were used to assess response to neoadjuvant, postoperative or salvage chemotherapy. Chi-square testing was used to evaluate the association between tumor grade and chemotherapy response. Ninety-one patients met inclusion criteria: 13 with grade 1, 29 with grade 2 and 49 with grade 3 tumors. Eighty four percent of patients received chemotherapy for recurrence, 12% for postoperative residual disease, and 4% in the neoadjuvant setting. The majority (85%) received carboplatin and paclitaxel. Forty-six percent (6/13) of grade 1, 72% (21/29) of grade 2 and 43% (21/49) of grade 3 tumors achieved an objective response. Grade 2 tumors were more likely to respond to chemotherapy compared to grade 3 tumors (72% vs. 43%, p = 0.02; Table 2), and specifically more likely to respond to carboplatin/paclitaxel (72% vs. 41%, p = 0.016). Median progression free survival for patients receiving chemotherapy for recurrence or progression was 9 months for grade 1, 8 months for grade 2, and 5 months for grade 3 tumors. Similar results between grade and treatment response were apparent in the subset of 37 patients with a recently re-assigned tumor grade (G2 88% vs. G3 44%, p = 0.032). In this series of endometrioid endometrial cancers, grade 2 tumors had the best measurable response to chemotherapy. PMID- 27354991 TI - Mesonephric adenocarcinoma of the cervix: Case report and literature review. AB - A mesonephric adenocarcinoma of the cervix is a very rare tumor deriving from remnants of the mesonephric duct. Differential diagnosis from other cervical carcinomas is difficult and little is known regarding its biological behavior, prognosis, and the optimal management strategy. We present a case of a mesonephric adenocarcinoma of the cervix with a comprehensive review of the existing literature. In this case a 66-year-old woman presented with postmenopausal vaginal bleeding. She was diagnosed with a FIGO stage IIB mesonephric adenocarcinoma of the cervix and treated with neoadjuvant chemoradiotherapy and a Wertheim hysterectomy. The recovery from surgery was uneventful and the patient remains with no evidence of disease with 2 years of follow-up. PMID- 27354992 TI - Actigraphic evaluation in patients with endometrial cancer. PMID- 27354993 TI - Correction of coagulopathy associated with non-bacterial thrombotic endocarditis (NBTE) by surgical debulking in a case of ovarian clear cell carcinoma. AB - *Ovarian cancer, particularly clear cell carcinoma, creates a hypercoagulable state.*This state can predispose to non-bacterial thrombotic endocarditis (NBTE).*NBTE can embolize and cause widespread arterial infarction.*NBTE is sometimes associated with a treatment refractory disseminated coagulopathy.*Surgical removal of the primary mass can sometimes reverse the coagulopathy. PMID- 27354994 TI - Solitary fibrous tumor of the greater omentum mimicking an ovarian tumor in a young woman. AB - We report a case of solitary fibrous tumor (SFT) of greater omentum in a young woman. SFT arising from the greater omentum can mimic a gynecologic neoplasm. SFTs are generally benign but some of them are malignant and have uncertain prognosis. An adequate follow-up is essential in these patients. PMID- 27354995 TI - Primary peritoneal carcinoma presenting as a Sister Mary Joseph's nodule: A case report and review of the literature. AB - Sister Mary Joseph's nodule is sometimes the first sign of an internal malignancy, including gastrointestinal, gynecological, or malignancy of unknown primary. It is rarely the sole presentation of a primary peritoneal cancer. In this report, we present the case of a 70-year-old female with umbilical drainage and a computed tomography scan consistent with solitary umbilical nodule. Excision of the nodule revealed adenocarcinoma of likely mullerian origin. Surgical staging did not show any evidence of malignancy with the exception of pelvic washings. She was considered to have primary peritoneal adenocarcinoma and was treated with adjuvant chemotherapy. PMID- 27354996 TI - Management of a rapidly enlarging new adnexal mass: a rare case of desmoplastic small round cell tumor of the ovary arising in pregnancy. AB - BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is an extremely rare sarcomatous tumor, which is most commonly seen in men. Clinicians managing a patient with a rapidly enlarging mass in pregnancy should be aware of the risk for malignancy. CASE: A 31-year-old woman was found to have a newly enlarged ovarian mass in the second trimester. She subsequently underwent a laparotomy for removal, with chemotherapy for presumed poorly differentiated ovarian malignancy. Ultimately she was diagnosed with a desmoplastic small round cell tumor of the ovary and had progression at time of delivery. Following cesarean delivery, she had a tumor reductive surgery. She has completed 12 cycles of intensive chemotherapy and is alive with disease at 14 months. CONCLUSION: Care should be taken not to delay evaluation of a rapidly enlarging mass in pregnancy. While this tumor type is extremely rare, a malignancy in pregnancy must be ruled out in this clinical scenario. PMID- 27354997 TI - A case of mesothelioma masquerading pre-operatively as ovarian cancer and brief review of the literature. AB - BACKGROUND: Malignant peritoneal mesothelioma (MPM) can masquerade as an ovarian epithelial neoplasm, with very similar presenting clinical symptoms and imaging findings. The gold standard in differentiating between these two diagnoses lies in tissue pathology. CASE REPORT: This is a case of MPM that was initially misdiagnosed as ovarian cancer based on family history, imaging, and surgical findings. Tissue diagnosis preoperatively would have changed the planned procedure. Retrospectively, after the diagnosis of MPM, the patient was found to have had an indirect exposure to asbestos through her father. CONCLUSIONS: This case highlights the importance of keeping a broad differential when diagnosing ovarian malignancies, collecting both family and social histories (including screening for exposure to asbestos), and the benefit of obtaining tissue diagnosis when MPM is suspected. PMID- 27354998 TI - Short-term morbidity in transdiaphragmatic cardiophrenic lymph node resection for advanced stage gynecologic cancer. AB - Ovarian cancer is commonly diagnosed at an advanced stage, with disease involving the upper abdomen. The finding of enlarged cardiophrenic lymph nodes (CPLNs) on pre-operative imaging often indicates the presence of malignant spread to the mediastinum. Surgical resection of CPLN through a transdiaphragmatic approach can help to achieve cytoreduction to no gross residual. A retrospective chart review was conducted on all patients who underwent transdiaphragmatic cardiophrenic lymph node resection from 8/1/11 through 2/1/15. All relevant pre-, intra-, and post-operative characteristics and findings were recorded. A brief description of the surgical technique is included for reference. Eleven patients were identified who had undergone transdiaphragmatic resection of cardiophrenic lymph nodes. Malignancy was identified in 18/21 (86%) of total lymph nodes submitted. The median number of post-operative days was 7. The overall post-operative morbidity associated with CPLN resection was low, with the most common finding being a small pleural effusion present on chest x-ray between POD# 3-5 (55%). Transdiaphragmatic CPLN resection is a feasible procedure with relatively minor short-term post-operative morbidities that can be used to achieve cytoreduction to no gross residual disease. PMID- 27354999 TI - Hemophagocytic lymphohistiocytosis as a paraneoplastic syndrome associated with ovarian dysgerminoma. AB - *Ovarian dysgerminoma associated with paraneoplastic fever, cytopenia and splenomegaly*Complete symptom resolution resulted from tumor resection and medical management*Non-hematolymphoid neoplasms are part of differential diagnosis in secondary HLH. PMID- 27355000 TI - Incidence and contributing factors to termination of the patient-physician relationship. AB - PURPOSE: Identify the incidence and factors contributing to the termination of gynecologic patient-physician relationships. METHODS: All patients terminated from the practice between January 2008 and December 2012 were identified. Charts were reviewed for demographic information, termination reason, and cancer diagnosis. RESULTS: In the five year study period, 8851 new patients presented to the division of gynecologic oncology. Within this cohort, 123 patient-physician relationships were terminated. Among terminated patients, missed appointments (63.4%), noncompliance to treatment (23.6%), disruptive behavior (10.6%), and drug abuse behavior (2.4%) were the key reasons for termination. While no patients were terminated for financial reason, statistical differences were found for those with Medicaid insurance (OR = 5; 95% CI: 3.4-7.1). Terminated patients were more likely to be younger, African American/Black, and have a diagnosis of GTD or cancer, particularly cervical cancer, when compared against all retained patients. CONCLUSION: The prevalence of patient-physician relationship termination was low at 1.4% (123/8851). However, the finding that the 52% of terminated patients had a diagnosis of cancer is concerning; 73% of which had stage III or greater disease, or were unstaged. We hope that the identification and quantification of reasons for termination and those at risk for termination, as well as the introduction of patient-navigators, will lead to improved methods to ensure patient compliance and retention. PMID- 27355001 TI - Leiomyosarcoma of the uterine cervix associated with pregnancy: A case report and review of literature. AB - *Management of cervical leiomyosarcoma in pregnancy requires a multidisciplinary approach.*Ovarian preservation is preferred in young patients with early stage cervical leiomyosarcoma.*Routine lymphadenectomy in patients with early stage cervical leiomyosarcoma is not useful. PMID- 27355002 TI - A non-pregnant woman with elevated beta-HCG: A case of para-neoplastic syndrome in ovarian cancer. AB - There is a broad range of possible diagnoses for an elevated beta human chorionic gonadotropin (beta-hCG) in the absence of intrauterine or ectopic pregnancy. When women of child bearing potential undergo evaluation for clinical trial, it is often unclear what course of evaluation to take when a pregnancy test is positive. We describe the clinical course of a patient with widely metastatic mucinous ovarian carcinoma with metastasis to the peritoneum, lymph nodes and liver. The patient was found to have a mildly elevated beta-hCG during initial evaluation for clinical trial. Extensive work up for ectopic pregnancy, trophoblastic disease, and phantom beta-hCG were negative. The patient's beta-hCG levels continued to rise until initiation of therapy. She was treated on a phase I protocol with restaging scans revealing a partial response. The beta-hCG was retested and declined in conjunction with her response, consistent with paraneoplastic beta-hCG. Here, we propose a decision making algorithm to evaluate a patient with an elevated beta-hCG undergoing assessment for clinical trial. PMID- 27355003 TI - Robotically assisted delayed total laparoscopic hysterectomy for placenta percreta. AB - BACKGROUND: The prevalence of morbidly adherent placenta has dramatically increased in the setting of the rising cesarean rate in the United States. Delayed surgical management of placenta accreta and its variants is emerging as methods that may significantly decrease bleeding and perioperative complications; however, optimal surgical approaches have not yet been determined. In this report, we present a case of robotic-assisted delayed interval hysterectomy in a patient with placenta percreta. METHOD: A minimally invasive approach, via a robotic-assisted total laparoscopic hysterectomy, was utilized for a 39-year-old gravida 9 para 3 with placenta percreta with placenta left in situ ten weeks after a tertiary cesarean section. EXPERIENCE: The robotic approach provided excellent visualization to facilitate fine planes of dissection, lower than expected estimated blood loss, and faster recover times when compared with conventional surgical approaches traditionally utilized for interval hysterectomies for placenta percreta. CONCLUSION: Robotic-assisted hysterectomy may be considered as an alternative to laparotomy for the delayed interval surgical management of morbidly adherent placenta percreta. PMID- 27355004 TI - Treatment and follow-up of malignant struma ovarii: Regarding two cases. AB - Malignant struma ovarii (SO) is a rare tumor, and as a consequence, treatments and follow-up procedures are not clearly established. Presented in this study are two cases of suspicious ovarian masses, resected and corresponding to malignant SO on histopathology. Similar to thyroid cancer, we proposed complementary radioiodine therapy ((131)I) after total thyroidectomy (no malignancy was observed at this level in our two patients). Patients underwent treatment with 3.7 GBq (131)I followed by post-therapy whole-body scintigraphy, which can detect residual disease or occult metastases. Thyroid remnant ablation increases the sensitivity and specificity of follow-up testing using serum thyroglobulin levels as a tumor marker. Our two patients remained disease-free for 3 and 5 years, respectively, after treatment. PMID- 27355005 TI - Symbiotic Efficiency of Native Rhizobia Nodulating Common Bean (Phaseolus vulgaris L.) in Soils of Western Kenya. AB - This study was conducted to determine the abundance and symbiotic efficiency of native rhizobia nodulating common bean in Kisumu and Kakamega, Kenya. Soil sampling was carried out in three farms that had been used for growing common bean for at least two seasons and one fallow land with no known history of growing common bean or inoculation. Abundance of soil rhizobia and symbiotic efficiency (SE) were determined in a greenhouse experiment. Native rhizobia populations ranged from 3.2 * 10(1) to 3.5 * 10(4) cells per gram of soil. Pure bacterial cultures isolated from fresh and healthy root nodules exhibited typical characteristics of Rhizobium sp. on yeast extract mannitol agar media supplemented with Congo red. Bean inoculation with the isolates significantly (p < 0.05) increased the shoot dry weight and nitrogen (N) concentration and content. The SE of all the native rhizobia were higher when compared to a reference strain, CIAT 899 (67%), and ranged from 74% to 170%. Four isolates had SE above a second reference strain, Strain 446 (110%). Our results demonstrate the presence of native rhizobia that are potentially superior to the commercial inoculants. These can be exploited to enhance bean inoculation programmes in the region. PMID- 27355006 TI - Pumice Characteristics and Their Utilization on the Synthesis of Mesoporous Minerals and on the Removal of Heavy Metals. AB - Wastewater treatment of some heavy metals was carried out by synthetic zeolite P1, which was prepared by alkaline hydrothermal treatment of the pumice. Both of the pumice raw materials and synthetic zeolite were investigated for their chemical phase composition, physical properties, and microstructure. The adsorption behavior of Na-zeolite P1 with respect to Co(+2), Cu(+2), Fe(+2), and Cd(+2) has been studied to be applied in the industrial wastewater treatment. Metal removal was investigated using synthetic solutions at different ions concentrations, time, and Na-P1 zeolite doses as well as constant temperature and pH. It is concluded that the optimum conditions for synthesis of highly active Na P1 zeolite from natural pumice raw material are one molar NaOH concentration, temperature at 80 degrees C, and one week as a crystallization time. In addition to the effect of time and zeolite dose as well as the ion concentration of the reaction efficiency for metals removals are recorded. PMID- 27355007 TI - Global Stability of an HIV-1 Infection Model with General Incidence Rate and Distributed Delays. AB - In this work an HIV-1 infection model with nonlinear incidence rate and distributed intracellular delays and with humoral immunity is investigated. The disease transmission function is assumed to be governed by general incidence rate f(T, V)V. The intracellular delays describe the time between viral entry into a target cell and the production of new virus particles and the time between infection of a cell and the emission of viral particle. Lyapunov functionals are constructed and LaSalle invariant principle for delay differential equation is used to establish the global asymptotic stability of the infection-free equilibrium, infected equilibrium without B cells response, and infected equilibrium with B cells response. The results obtained show that the global dynamics of the system depend on both the properties of the general incidence function and the value of certain threshold parameters R 0 and R 1 which depends on the delays. PMID- 27355008 TI - Iterative Robust Capon Beamforming with Adaptively Updated Array Steering Vector Mismatch Levels. AB - The performance of the conventional adaptive beamformer is sensitive to the array steering vector (ASV) mismatch. And the output signal-to interference and noise ratio (SINR) suffers deterioration, especially in the presence of large direction of arrival (DOA) error. To improve the robustness of traditional approach, we propose a new approach to iteratively search the ASV of the desired signal based on the robust capon beamformer (RCB) with adaptively updated uncertainty levels, which are derived in the form of quadratically constrained quadratic programming (QCQP) problem based on the subspace projection theory. The estimated levels in this iterative beamformer present the trend of decreasing. Additionally, other array imperfections also degrade the performance of beamformer in practice. To cover several kinds of mismatches together, the adaptive flat ellipsoid models are introduced in our method as tight as possible. In the simulations, our beamformer is compared with other methods and its excellent performance is demonstrated via the numerical examples. PMID- 27355009 TI - Nontraumatic Lesions of the Clavicle in a Paediatric Population: Incidence and Management. AB - Background. The incidence of paediatric nontraumatic clavicle lesions is unknown and there is limited literature regarding the management of such patients. Methods. A review of a prospectively complied radiological database held at the study was conducted for a defined 10-year period. The study centre is the only paediatric service available for a defined catchment population. The case notes of all patients with nontraumatic lesions were reviewed, and the mode of presentation, the diagnostic dilemmas, and the management were recorded. Results. A total of 2133 clavicle radiographs were performed during the study period, with only five having a nontraumatic history. The overall incidence of paediatric nontraumatic clavicle lesions was 0.38 per 100,000 per year. Three patients were diagnosed with chronic recurrent osteomyelitis, one with chronic bifocal osteomyelitis, and one with Langerhans cell histiocytosis. All patients with osteomyelitis demonstrated a typical natural history of a chronic relapsing remitting infection. Three underwent bone biopsy; however, no organism was identified. Conclusion. This study demonstrated that the incidence of nontraumatic clavicle lesions is small, and those patients presenting with osteomyelitis should not routinely undergo a bone biopsy and close observation with the appropriate antibiotic therapy is advised. PMID- 27355010 TI - Biochemical and Ultrastructural Changes in Sida cordifolia L. and Catharanthus roseus L. to Auto Pollution. AB - Auto pollution is the by-product of our mechanized mobility, which adversely affects both plant and human life. However, plants growing in the urban locations provide a great respite to us from the brunt of auto pollution by absorbing the pollutants at their foliar surface. Foliar surface configuration and biochemical changes in plant species, namely, Sida cordifolia L. and Catharanthus roseus L. grown at roadside (polluted site 1, Talkatora; polluted site 2, Charbagh) in Lucknow city and in the garden of the university campus, which has been taken as reference site, were investigated. It was observed that air pollution caused by auto exhaust showed marked alterations in photosynthetic pigments (chlorophyll, carotenoid, and phaeophytin), and relative water content was reduced while antioxidative enzymes like catalase and peroxidase were found to be enhanced. The changes in the foliar configuration reveal marked alteration in epidermal traits, with decreased number of stomata, stomatal indices, and epidermal cells per unit area, while length and breadth of stomata and epidermal cells were found to be increased in leaves samples wich can be used as biomarkers of auto pollution. PMID- 27355012 TI - Superoptimal Rate of Convergence in Nonparametric Estimation for Functional Valued Processes. AB - We consider the nonparametric estimation of the generalised regression function for continuous time processes with irregular paths when the regressor takes values in a semimetric space. We establish the mean-square convergence of our estimator with the same superoptimal rate as when the regressor is real valued. PMID- 27355011 TI - Outcome in Women with Traumatic Brain Injury Admitted to a Level 1 Trauma Center. AB - Background. The aim of this study was to compare acute outcome between men and women after sustaining a traumatic brain injury (TBI). Methods. A total of 5,642 patients admitted to the Traumatic Brain Injury Program of the McGill University Health Centre-Montreal General Hospital between 2000 and 2011 and diagnosed with a TBI were included in the study. The overall percentage of women with TBI was 30.6% (n = 1728). Outcome measures included the length of stay (LOS), the Extended Glasgow Outcome Scale (GOSE), the functional independence measure instrument (FIM), discharge destination, and mortality rate. Results. LOS, GOSE, the FIM ratings, and discharge destination did not show significant differences between genders once controlling for several confounding variables and running the appropriate diagnostic tests (P < 0.05). However, women had less chance of dying during their acute care hospitalization than men of the same age, with the same TBI severity and following the same mechanism of injury. Although gender was a statistically significant predictor, its contribution in explaining variation in mortality was small. Conclusion. More research is needed to better understand gender differences in mortality; as to date, the research findings remain inconclusive. PMID- 27355013 TI - Proteomic Characterization of Lytic Bacteriophages of Staphylococcus aureus Isolated from Sewage Affluent of India. AB - Staphylococcus aureus is a Gram-positive bacterium that causes a variety of diseases, including bovine mastitis, which has severe economic consequences. Standard antibiotic treatment results in selection of resistant strains, leading to need for an alternative treatment such as bacteriophage therapy. Present study describes isolation and characterization of a staphylococcal phage from sewage samples. S. aureus isolates obtained from microbial type culture collection (MTCC), Chandigarh, India, were used to screen staphylococcal phages. A phage designated as PhiMSP was isolated from sewage samples by soft agar overlay method. It produced clear plaques on tryptone soya agar overlaid with S. aureus. Transmission electron microscopy revealed that the phage had an icosahedral symmetry. It had 5 major proteins and possessed a peptidoglycan hydrolase corresponding to 70 kDa. PhiMSP infection induced 26 proteins to be uniquely expressed in S. aureus. This phage can be proposed as a candidate phage to treat staphylococcal infections. PMID- 27355014 TI - Endosymbiotic Bacteria Associated with the Mealy Bug, Rhizoecus amorphophalli (Hemiptera: Pseudococcidae). AB - The mealy bug, Rhizoecus amorphophalli, is a menace to the aroid farmers due to the intensive infestation on stored tubers. Spraying of pesticides was able to control this pest but it always left a chance for fungal growth. Bacterial endosymbionts associated with the insects provide several benefits to their host. Since such endosymbionts play a vital role even in the physiology of their host, revealing the types of bacteria associated with mealy bug will give basic information, which may throw light on the management of this noxious pest. The present study is the first to identify bacterial endosymbionts associated with R. amorphophalli employing phenotypic characterization and 16S rDNA sequencing. Three culturable bacteria, namely, Bacillus subtilis, Staphylococcus gallinarum, and Staphylococcus saprophyticus, were isolated from R. amorphophalli. Moreover, the antibiotic susceptibility tests against the isolated bacteria showed that all the isolates were susceptible to the three antibiotics tested, except cephalexin. Recently, endosymbionts are used as effective biocontrol agents (BCAs) and the present study will stand as a connecting link in identification and effective utilization of these endosymbionts as BCAs for management of R. amorphophalli. PMID- 27355015 TI - Oxya hyla hyla (Orthoptera: Acrididae) as an Alternative Protein Source for Japanese Quail. AB - Nutrient composition of the grasshoppers Oxya hyla hyla showed that they are a rich nutrient source containing 687.7 g protein/kg of dry body weight. Their antinutrient values fell within nutritionally acceptable values of the poultry bird Coturnix japonica japonica (Japanese quail). The most required essential amino acids and fatty acids were also present in sufficient amount. For feeding trial nine diets were formulated on an equal crude protein (230 g/kg) basis with grasshopper meal, fish meal, and soybean meal. Three sets of diets with grasshopper meal were prepared with 50 g/kg, 100 g/kg, and 150 g/kg grasshopper of total feed. Similarly, other diet sets were prepared with fish meal and also with soybean meal. Results were compared with another group of Japanese quails fed on a reference diet that was considered as control. Two experiments were conducted with a total number of 600, seven-day-old, Japanese quails. In experiment 1 for determination of growth performance, quails were randomly distributed into ten groups of males and ten groups of females containing 30 birds each. In experiment 2 for determination of laying performance, identical ten groups were prepared in ten repetitions (2 females and 1 male in each group) from the six-week-old birds of experiment 1. Birds of diet set GM2 have gained the highest body weight (male 4.04 g/bird/day; female 5.01 g/bird/day) followed by birds of FM3 diet set (male 3.72 g/bird/day; female 4.40 g/bird/day), whereas birds of reference diet have gained 3.05 g/bird/day for male and 3.23 g/bird/day for female. Feed conversion ratio (FCR) of birds fed with GM2 was the lowest (male 3.33; female 2.97) whereas FCR of R group was higher (male 4.37; female 4.65) than grasshopper meal and fish meal based diets. Hen day production percentage was higher (72.2) in GM2 group, followed by FM3 (63.5) group. R group had lower 1st egg weight (9.0 g), weight gain (8.2 g), percentage of hen day production (41.8%), higher feed intake (33.6 g/day/bird), and age at 1st laid egg than the grasshopper meal and fish meal based diets. So growth and laying performance of the birds were significantly better in grasshopper meal and fish meal added diet fed sets than the reference diet fed group; among all the dietary groups 100 g/kg grasshopper meal added diet mostly gave significantly better results followed by 150 g/kg fish meal added diets. It was ascertained that the O. hyla hyla meal had pronounced positive response on the birds. So, the quails could be easily fed 100 g/kg grasshopper meal added diet as it was the most suitable alternative feedstuff compared to the conventional protein source based diets. PMID- 27355016 TI - Potential Interaction of Green Tea Extract with Hydrochlorothiazide on Diuretic Activity in Rats. AB - Treatment of ischemic hypertensive patients with hydrochlorothiazide can precipitate cardiac arrhythmias. The present study was undertaken to evaluate the diuretic potential of green tea alone and its effects on hydrochlorothiazide in interactive groups. Rats were treated with high (500 mg/kg, p.o.) and low (100 mg/kg, p.o.) dose of green tea extract in alone and interactive groups for 30 days. Standard, high, and low dose interactive groups received hydrochlorothiazide (10 mg/kg, p.o.) on the day of experiment. Effect of different treatments was that assessed by evaluating diuretic action, diuretic activity, percentage of saline load excreted, and sodium and potassium levels in urine. Green tea in both high and low doses showed significant diuretic potential and when it is combined with hydrochlorothiazide resulted in significant improvement in the activity compared to hydrochlorothiazide alone treated group. It can be concluded that green tea extract when combined with hydrochlorothiazide showed significant increase in diuretic activity. Most important observation of the present study is even though the combination increases the diuretic potential, it is responsible for decrease in urinary potassium loss. PMID- 27355017 TI - The Usefulness of Endothelial Cell Adhesion Molecules and Anti-C1q Antibody in Monitoring Systemic Lupus Erythematosus Disease Activity. AB - Objectives. The study was conducted to determine the correlation of ICAM-1, VCAM 1, and anti-C1q antibody levels with SLE disease activity index (SLEDAI) and standard SLE disease activity immunological markers (anti-dsDNA and sera C3 and C4). Study Design. This was a cross-sectional study. Materials and Methods. Blood samples were obtained from 95 SLE patients (45 active SLE and 50 nonactive SLE) and 50 controls. The subjects were assessed using SLEDAI and score of more than five is determined as having active SLE. The sera were tested for serum ICAM-1, VCAM-1, and anti-C1q (ELISA), anti-dsDNA (CLIFT), serum C3, and serum C4 (immunonephelometry). Results. Anti-dsDNA and anti-C1q antibody showed good positive correlations with SLEDAI (r = 0.529, P < 0.001 and r = 0.559, P < 0.001, resp.). VCAM-1 and sera C3 and C4 showed fair correlation with SLEDAI (r = 0.294, P = 0.004; r = -0.312, P = 0.002; and r = -0.382, P < 0.001, resp.). ICAM-1 level showed no significant correlation with SLEDAI (P = 0.062). There were significant correlations of VCAM-1 and anti-C1q antibody with anti-dsDNA (r = 0.226, P = 0.006 and r = 0.511, P < 0.001, resp.). VCAM-1 showed poor inverse correlation with serum C3 (r = -0.183, P = 0.028) and fair inverse correlation with serum C4 (r = -0.251, P = 0.002). Anti-C1q antibody demonstrated fair inverse correlation with both sera C3 and C4 (r = -0.420, P <= 0.001 and r = -0.398, P < 0.001, resp.). However, ICAM-1 showed no significant correlation with anti-dsDNA and sera C3 and C4 (P = 0.259, P = 0.626 and P = 0.338, resp.). Conclusions. The serum levels of anti-C1q antibody in SLE patients showed the best correlation with the SLEDAI and standard immunological tests for SLE disease activity. These data support that anti-C1q antibody is a useful marker for monitoring SLE global disease activity. The potential of VCAM-1 needs further confirmation. PMID- 27355018 TI - 350 nm Broadband Supercontinuum Generation Using Dispersion Engineered Near Zero Ultraflat Square-Lattice PCF around 1.55 MUm and Fabrication Tolerance Analysis. AB - In this work, a new design of ultraflat dispersion PCF based on square-lattice geometry with all uniform air holes towards broadband smooth SCG around the C band of wavelength has been presented. The air hole of the inner ring was infiltrated with liquid of certain refractive indices. Numerical investigations establish a near zero ultraflattened dispersion of 0 +/- 0.78 ps/nm/km in a wavelength range of 1496 nm to 2174 nm (678 nm bandwidth) covering most of the communications bands with the first zero dispersion wavelength around 1.54 MUm. With the optimized ultraflattened fiber, we have achieved a broadband SC spectrum with FWHM of 350 nm with the central wavelength of 1550 nm with less than a meter long of the fiber by using a picosecond pulse laser. We have also analyzed the sensitivity of the optimized dispersion design by small variations from the optimum value of the geometrical structural parameters. Our investigations establish that for a negative change of PCF parameters, the profile retains the smooth and flat SCG spectra; however, for a positive change, the smooth and a flat spectrum is lost. The new design of the fiber will be capable of covering huge diverse field of DWDM sources, spectroscopy, meteorology, optical coherence tomography, and optical sensing. PMID- 27355019 TI - Determining Information on Cardiology Disease Risk Factors of Disease in Women. AB - In an attempt to decrease the rate of mortality from cardiovascular diseases, first cardiovascular risk factors should be controlled. This study was carried out to reveal the level of knowledge about cardiovascular disease risk factors in women who presented to a primary healthcare center in Erzurum, Turkey, and the prevalence of such risk factors. Our study is a descriptive one and its data were collected between February and April 2013. The study included 168 women who presented to Filiz Dolunay Family Healthcare Center and who met the criteria and agreed to participate in the study. It was found that 22.6% of the women did not exercise at all above normal range, 53.6% of them had weights above normal, 23.8% smoked, and 22% had hypertension, type 2 diabetes, cholesterol, or excess fat around their waist. It was concluded that, although women were knowledgeable, they did not put this into practice in their lives. PMID- 27355020 TI - Development and Validation of Stability Indicating Spectroscopic Method for Content Analysis of Ceftriaxone Sodium in Pharmaceuticals. AB - A simple, selective, and stability indicating spectroscopic method has been selected and validated for the assay of ceftriaxone sodium in the powder for injection dosage forms. Proposed method is based on the measurement of absorbance of ceftriaxone sodium in aqueous medium at 241 nm. The method obeys Beer's law in the range of 5-50 MUg/mL with correlation coefficient of 0.9983. Apparent molar absorptivity and Sandell's sensitivity were found to be 2.046 * 10(3) L mol(-1) cm(-1) and 0.02732 MUg/cm(2)/0.001 absorbance units. This study indicated that ceftriaxone sodium was degraded in acid medium and also underwent oxidative degradation. Percent relative standard deviation associated with all the validation parameters was less than 2, showing compliance with acceptance criteria of Q2 (R1), International Conference on Harmonization (2005) guidelines. Then the proposed method was successfully applied to the determination of ceftriaxone sodium in sterile preparation and results were comparable with reported methods. PMID- 27355021 TI - Formulation Development and Characterization of Meclizine Hydrochloride Sublimated Fast Dissolving Tablets. AB - The intention of present research is to formulate and develop the meclizine hydrochloride fast dissolving tablets using sublimation method to enhance the dissolution rate. In this study an attempt was made to fasten the drug release from the oral tablets by incorporating the superdisintegrants and camphor as sublimating agent. The prepared fast dissolving tablets were subjected to precompression properties and characterized for hardness, weight variation, friability, wetting time, water absorption ratio, and disintegration time. From in vitro release studies, the formulation F9 exhibited fast release profile of about 98.61% in 30 min, and disintegration time 47 sec when compared with other formulations. The percent drug release in 30 min (Q 30) and initial dissolution rate for formulation F9 was 98.61 +/- 0.25%, 3.29%/min. These were very much higher compared to marketed tablets (65.43 +/- 0.57%, 2.18%/min). The dissolution efficiency was found to be 63.37 and it is increased by 1.4-fold with F9 FDT tablets compared to marketed tablets. Differential scanning calorimetry and Fourier transform infrared spectroscopy studies revealed that there was no possibility of interactions. Thus the development of meclizine hydrochloride fast dissolving tablets by sublimation method is a suitable approach to improve the dissolution rate. PMID- 27355022 TI - Novel Organically Modified Core-Shell Clay for Epoxy Composites-"SOBM Filler 1". AB - Preparation of a novel organically modified clay from spent oil base drilling mud (SOBM) that could serve as core-shell clay filler for polymers is herein reported. Due to the hydrophilic nature of clay, its compatibility with polymer matrix was made possible through modification of the surface of the core clay sample with 3-aminopropyltriethoxysilane (3-APTES) compound prior to its use. Fourier transform infrared (FT-IR) spectroscopy was used to characterize clay surface modification. Electron dispersive X-ray diffraction (EDX) and scanning electron microscopy (SEM) were used to expose filler chemical composition and morphology, while electrophoresis measurement was used to examine level of filler dispersion. Results show an agglomerated core clay powder after high temperature treatment, while EDX analysis shows that the organically modified clay is composed of chemical inhomogeneities, wherein elemental compositions in weight percent vary from one point to the other in a probe of two points. Micrographs of the 3-APTES coupled SOBM core-shell clay filler clearly show cloudy appearance, while FT-IR indicates 25% and 5% increases in fundamental vibrations band at 1014 cm(-1) and 1435 cm(-1), respectively. Furthermore, 3-APTES coupled core-shell clay was used to prepare epoxy composites and tested for mechanical properties. PMID- 27355023 TI - Next Generation Sequencing Analysis of Biofilms from Three Dogs with Postoperative Surgical Site Infection. AB - The composition of biofilms in chronic wound infections of dogs is unclear. In the present study, histologically identified biofilms attached to sutures in chronically infected wounds of three dogs were examined by next generation sequencing of total DNA extracted from formalin-fixed and paraffin-embedded tissue samples. The analysis identified an inhomogeneous bacterial composition in three tissues containing biofilms. Some of the identified bacterial families such as Staphylococci and Streptococci have been found before in biofilms associated with human and canine wounds but in this study were quantitatively in the minority. The majority of the reads classified as bacterial sequences had the highest identity with sequences belonging to the Porphyromonadaceae, Deinococcaceae, Methylococcaceae, Nocardiaceae, Alteromonadaceae, and Propionibacteriaceae and thus taxons of so far minor relevance in veterinary medicine. PMID- 27355024 TI - Clinical Applications of Procalcitonin in Pediatrics: An Advanced Biomarker for Inflammation and Infection-Can It Also Be Used in Trauma? AB - Background. Procalcitonin is a small molecular peptide that has gained increased support as an adjunct diagnostic marker of infection in the adult population; the concordant body of evidence for the use of procalcitonin in pediatric populations is far less complete. Objectives. Our objective is to review the current evidence supporting the utilization of procalcitonin in children in a variety of clinical scenarios including SIRS, sepsis, burns, and trauma and to identify existing knowledge gaps. Methods. A thorough review of the literature was performed utilizing PubMed. We focused on using meta-analysis from adult populations to review current practices in interpretation and methodology and find concordant pediatric studies to determine if the same applications are validated in pediatric populations. Results. Current evidence supports the usage of procalcitonin as both a sensitive and a specific marker for the differentiation of systemic inflammatory response syndrome from sepsis in pediatrics with increased diagnostic accuracy compared to commonly used biomarkers including complete blood counts and C-reactive protein. Conclusions. Although the body of evidence is limited, initial observations suggest that procalcitonin can be used in pediatric trauma and burn patients as both a prognostic and a diagnostic marker, aiding in the identification of infection in patients with extensive underlying inflammation. PMID- 27355025 TI - Efficacy of Two Irrigants Used with Self-Adjusting File System on Smear Layer: A Scanning Electron Microscopy Study. AB - Mechanical instrumentation of root canals produces a smear layer that adversely affects the root canal seal. The aim of this study was to evaluate efficacy of MTAD and citric acid solutions used with self-adjusting file (SAF) system on smear layer. Twenty-three single-rooted human teeth were used for the study. Canals were instrumented manually up to a number 20 K file size. SAF was used to prepare the root canals. The following groups were studied: Group 1: MTAD + 5.25% NaOCl, Group 2: 20% citric acid + 5.25% NaOCl, and Group 3: Control (5.25% NaOCl). All roots were split longitudinally and subjected to scanning electron microscopy. The presence of smear layer in the coronal, middle, and apical thirds was evaluated using a five-score evaluation system. Kruskal-Wallis and Mann Whitney U tests were used for statistical analysis. In the coronal third, Group 2 exhibited the best results and was statistically different froms the other groups (P < 0.05). There was not a significant difference among the three thirds of groups according to in-group comparisons (P > 0.05). The solutions used in Group 1 and 2 could effectively remove smear layer in most of the specimens. However, citric acid was more effective than MTAD in the three thirds of the canal. PMID- 27355026 TI - Preservation of Involved Teeth Associated with Large Dentigerous Cysts. AB - Dentigerous cysts (DCs) are benign odontogenic cysts that are associated with the crowns of permanent teeth. The purpose of this study is to describe the management of DCs in four children. Four boys aged between 7 and 9 years were referred to our clinics with the complaints of intraoral alveolar swelling or facial asymmetry on the affected area. The panoramic radiographies showed large, well-defined radiolucent lesions associated with the deciduous teeth and displaced tooth buds. The treatment consisted of the extraction of the involved deciduous tooth and marsupialization of the cyst to allow eruption of the permanent tooth. Permanent teeth displaced by the DCs in three cases erupted spontaneously within one-year period. The case with horizontally displaced permanent tooth was managed by replantation. This is the first time that underlying permanent tooth in a DC case was intentionally replanted. PMID- 27355028 TI - Review of a Few Selected Theories of Plates in Bending. AB - The author's recent investigations on plate theories form the basis to review development of plate theories. In spite of several review articles on plate theories reported in the literature, the present work is essentially due to Jemielita's inspiring article (1993). It is shown that methods of analysis based on vertical displacement as domain variable deal with solution of associated torsion problem in bending of plates. It is essential to use vertical displacement as face variable instead of domain variable in proper analysis of bending problems. PMID- 27355027 TI - Are Attributes of Pregnancy and the Delivery Room Experience Related to Development of Autism? A Review of the Perinatal and Labor Risk Factors and Autism. AB - Autism is a neurodevelopmental disorder marked by severe deficits in social communication and interactions. It is a complex condition that lacks an established preventive method, warranting a need for research to identify possible environmental triggers. The identification of external factors particularly perinatal risk factors forms the initial critical step in preventing and alleviating risks. We conducted a literature review to assess evidence suggested in the worldwide literature. Perinatal risk factors that have a suggested association include beta2 adrenergic receptor agonists, labor induction and augmentation, maternal infection and disease (i.e., antiphospholipid syndrome), antiepileptic drugs, cocaine use, and oral supplements. Smoking has not been found to have a direct association. Pollutants, selective serotonin reuptake inhibitors, artificial insemination, and fertility medications may have a link, but results are often conflicted. Factors related to the delivery room experience may be associated with meconium aspiration syndrome, birth weight, and labor time. Several risk factors during the pregnancy and labor periods have been associated with autism; yet further studies with large populations are needed to establish definitive associations. The fact that several risk factors during the prenatal and labor periods are implicated in autism should prompt the medical community to focus on the pregnancy and labor periods as preventive measures to curb the incidence of autism. PMID- 27355029 TI - Perception of Dental Professionals towards Biostatistics. AB - Biostatistics is becoming an integral part of dental sciences. Awareness regarding the subject is not thoroughly assessed in the field of dentistry. So the study was conducted to assess dental professionals' knowledge, attitude, and perception toward biostatistics at an academic dental institution. An anonymous cross-sectional questionnaire survey was conducted among all the faculty and postgraduate students of two dental colleges in Moradabad, Uttar Pradesh. The responses were assessed on 5-point likert scale. The survey response rate was 73.71%. Two-thirds of respondents believed biostatistics to be a difficult subject and at the same time half of them did not consider it to be more difficult than other subjects in dentistry. Females were less competent than males in applying biostatistical skills which was found to be statistically significant. Results suggested that dentists with research or academics as an adjunct to their clinical practice had better command over the subject. The current study shows that there is lack of command over the subject of biostatistics among dental professionals although they were aware of its importance in dentistry. There is a need of changing the training pattern of biostatistics for dental professionals which would make them confident enough to apply biostatistics in their clinical practice. PMID- 27355030 TI - Embryonic Development of Heart in Indian Buffalo (Bubalus bubalis). AB - The present study was conducted on 35 buffalo foetuses from 0.9 cm CVRL (32 days) to 99.5 cm CVRL (298 days) to observe the morphogenesis and histogenesis of heart. The study revealed that, in 0.9 cm CVRL buffalo foetus, heart was unseptated and tubular which was clearly divided into common atrial chamber dorsally, primitive ventricles ventrally, primitive outflow tract with bulbous cordis region proximally, and aortic sac distally at 1.2 cm CVRL. Septum primum appeared at 1.9 cm CVRL whereas the truncal swellings and fold of interventricular septum appeared at 2.5 cm CVRL foetus. At 3.0 cm CVRL septum primum, endocardial cushions, septum secundum, and foramen ovale were observed. At 7.6 cm CVRL the endocardial cushions fused to form right and left atrioventricular openings and ventricular apex became pointed. Interventricular canal was obliterated and four-chambered heart was recognised along with atrioventricular valve, chordae tendineae, and papillary muscles in 8.7 cm CVRL (66 days) buffalo foetus. The endocardium as well as epicardium of the atria was thicker as compared to ventricle, whereas the myocardium of atria was thin as compared to ventricles in all the age groups. All the internal structures of heart were well differentiated from 50 cm CVRL onwards. The detailed structural components of buffalo heart during prenatal period have been discussed in the present paper. PMID- 27355031 TI - Remarks on Pre-I-Regular Pre-I-Open Sets. AB - We deal with the new class of pre-I-regular pre-I-open sets in which the notion of pre-I-open set is involved. We characterize these sets and study some of their fundamental properties. We also present other notions called extremally pre-I disconnectedness, locally pre-I-indiscreetness, and pre-I-regular sets by utilizing the notion of pre-I-open and pre-I-closed sets by which we obtain some equivalence relation for pre-I-regular pre-I-open sets. PMID- 27355032 TI - Asymptomatic Malaria and Associated Risk Factors among School Children in Sanja Town, Northwest Ethiopia. AB - Introduction. Asymptomatic malaria is prevalent in highly endemic areas of Africa and is new challenge for malaria prevention and control strategies. Objective. To determine the prevalence of asymptomatic malaria and associated risk factors among school children in Sanja Town, northwest Ethiopia. Methods. A cross sectional study was conducted from February to March 2013, on 385 school children selected using stratified proportionate systematic sampling technique. Pretested questionnaire was used to collect sociodemographic data and associated risk factors. Giemsa-stained thin and thick blood films were examined for detection, identification, and quantification of malaria parasites. Data were entered and analyzed using SPSS 20.0 statistical software. Multivariate logistic regression was done for assessing associated risk factors and proportions for categorical variables were compared using chi-square test. P values less than 0.05 were taken as statistically significant. Results. The prevalence of asymptomatic malaria was 6.8% (n = 26). The majority of parasitemic study participants had low parasite density 65.5% (17/26). Level of grade, age, bed net usage, and frequent exposure to malaria infection were associated with risk of asymptomatic malaria. Conclusion. Asymptomatic malaria was low in this study area and is associated with level of grade, age, bed net usage, and frequent exposure to malaria infection. PMID- 27355033 TI - Effect of Coronary Computed Tomography Angiography Disease Burden on the Incidence of Recurrent Chest Pain. AB - Introduction. The purpose of this study is to investigate chest pain evaluations after initial coronary computed tomography angiography (CCTA) based upon coronary artery disease (CAD) burden. Methods. CCTA results of 1,518 patients were grouped based on the CCTA results into no CAD, nonobstructive CAD (<50% maximal diameter stenosis), or obstructive CAD (>=50% stenosis). Chest pain evaluation after initial CCTA and rates of major adverse cardiovascular events (MACE) defined as the incidence of all-cause mortality, nonfatal MI, ischemic stroke, and late revascularization (>90 days following CCTA) were evaluated. Results. MACE rates were higher with obstructive CAD compared to nonobstructive CAD and no CAD (8.9% versus 0.7%, P < 0.001; 8.9 versus 1.6%, P < 0.001). One hundred seventy-four patients (11.5%) underwent evaluation for chest pain after index CCTA with rates significantly higher with obstructive CAD compared to both nonobstructive CAD and no CAD (7.5% versus 13.9% versus 17.8%, P < 0.001). The incidence of repeat testing was more frequent in patients with obstructive CAD (no CAD 36.5% versus nonobstructive CAD 54.9% versus obstructive CAD 67.7%, P = 0.015). Conclusion. Absence of obstructive disease on CCTA is associated with lower rates of subsequent evaluations for chest pain and repeat testing with low MACE event rates over a 22-month followup. PMID- 27355034 TI - Congenital Aniridia: Clinic, Genetics, Therapeutics, and Prognosis. AB - Congenital aniridia is a rare condition related to a deficiency in the PAX6 gene expression, which may occur as a result of a family inheritance or a sporadic occurrence. Additionally, this condition may occur as an isolated ocular phenotype or in association with a systemic syndrome. The most common abnormality is iris hypoplasia; however, a panocular disease which also affects the cornea, anterior chamber of the eye, lens, and the posterior segment with presence of optic nerve and foveal hypoplasia is also evident. The development of keratopathy, glaucoma, and cataract is frequent and its presence has implications in the patient's visual acuity. Managing aniridia is challenging since the focus is on treating the previously mentioned disorders, and the outcomes are often disappointing. In this paper, we shall review the epidemiology, pathophysiology, and clinical characteristics of patients with aniridia. We shall also make a review of the therapeutic options for the several conditions affecting this syndrome and consider the genetics and prognostic factors. PMID- 27355035 TI - Disease Modifying Therapy in Multiple Sclerosis. AB - Multiple sclerosis is an autoimmune disease of the central nervous system characterized by inflammatory demyelination and axonal degeneration. It is the commonest cause of permanent disability in young adults. Environmental and genetic factors have been suggested in its etiology. Currently available disease modifying drugs are only effective in controlling inflammation but not prevention of neurodegeneration or accumulation of disability. Search for an effective neuroprotective therapy is at the forefront of multiple sclerosis research. PMID- 27355036 TI - Minimally Invasive Management of Iatrogenic Ureteral Injuries with Ureteroscope Facilitated by Holmium Yttrium-Aluminum-Garnet Laser. AB - The ureter is vulnerable during general, gynecologic, and urologic surgeries. The traditional open surgical approaches to treating the iatrogenic ureteral injuries have shown several disadvantages such as relatively high rate of severe complications. Although the applications of endourological techniques for management of lower ureteral strictures have been routinely introduced over the last 10 years, most of the different modalities were based on the utilization of hydrophilic instruments that can facilitate the traversal of strictures surrounded by the sutures with gradually increasing force. Interestingly, we have revealed the Ho:YAG laser as the outstanding auxiliary approach to incising the sutures during the ureteroscopy for its well-controlled penetration depth, minimal scarring, and precise cutting. As far as we know, the combined utilization of Ho:YAG laser to incise the sutures responsible for the strictures and double J ureteral stent for drainage has not been extensively reported. Normal ureters of the patients managed by this novel approach were shown by the follow-up 3-4 months later, which demonstrated that the available technique was promising to effectively treat the iatrogenic ureteral injuries. PMID- 27355038 TI - Effect of Stiffness on Reflection and Transmission of Waves at an Interface between Heat Conducting Elastic Solid and Micropolar Fluid Media. AB - The present investigation is concerned with the propagation of waves at an imperfect boundary of heat conducting elastic solid and micropolar fluid media. The amplitude ratios of various reflected and transmitted waves are obtained in a closed form due to incidence of longitudinal wave (P-wave), thermal wave (T wave), and transverse wave (SV-wave). The variation of various amplitude ratios with angle of incidence is obtained for normal force stiffness, transverse force stiffness, thermal contact conductance, and perfect bonding. Numerical results are shown graphically to depict the effect of stiffness and thermal relaxation times on resulting quantities. Some particular cases are also deduced in the present investigation. PMID- 27355039 TI - Study of Protoscolicidal Effects of Hypertonic Glucose on Protoscolices of Hydatid Cyst at Different Concentrations and Exposure Times. AB - Surgical operation is the treatment of choice for hydatid cyst. To date, many protoscolicidal substances have been used for inactivation of hydatid cyst contents but most of these compounds may produce several side effects. The aim of this study was to evaluate the protoscolicidal effects of hypertonic glucose on protoscolices of hydatid cyst at different concentrations and exposure times. Protoscolices were obtained aseptically from the livers of slaughtered sheep at Qazvin abattoir, Iran. Protoscolices were exposed to different concentrations of hypertonic glucose (10%, 15%, 20%, 25%, 30%, 40%, and 50%) at different times (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, and 60 min). Viability of protoscolices was evaluated by 0.1% eosin and the movement of protoscolices flame cells. The highest protoscolicidal effect (100%) of hypertonic glucose was obtained at concentrations 40% and 50% following 40 and 20 min exposure times, respectively. Some protoscolicidal agents show a variety of dangerous complications such as biliary tract fibrosis and liver necrosis; however, hypertonic glucose especially at a concentration of 40% may demonstrate less side effects compared with glucose 50%. Further in vivo investigations are suggested. PMID- 27355040 TI - MHD Flow of the Micropolar Fluid between Eccentrically Rotating Disks. AB - This analytical investigation examines the magnetohydrodynamic flow problem of an incompressible micropolar fluid between the two eccentrically placed disks. Employing suitable transformations, the flow governing partial differential equations is reduced to ordinary differential equations. An exact solution representing the different flow characteristic of micropolar fluid has been derived by solving the ordinary differential equations. Analysis of the flow characteristics of the micropolar fluid has been done graphically by varying the Reynolds number and the Hartmann number. This analysis has been carried out for the weak and strong interactions. PMID- 27355037 TI - Transendothelial Transport and Its Role in Therapeutics. AB - Present review paper highlights role of BBB in endothelial transport of various substances into the brain. More specifically, permeability functions of BBB in transendothelial transport of various substances such as metabolic fuels, ethanol, amino acids, proteins, peptides, lipids, vitamins, neurotransmitters, monocarbxylic acids, gases, water, and minerals in the peripheral circulation and into the brain have been widely explained. In addition, roles of various receptors, ATP powered pumps, channels, and transporters in transport of vital molecules in maintenance of homeostasis and normal body functions have been described in detail. Major role of integral membrane proteins, carriers, or transporters in drug transport is highlighted. Both diffusion and carrier mediated transport mechanisms which facilitate molecular trafficking through transcellular route to maintain influx and outflux of important nutrients and metabolic substances are elucidated. Present review paper aims to emphasize role of important transport systems with their recent advancements in CNS protection mainly for providing a rapid clinical aid to patients. This review also suggests requirement of new well-designed therapeutic strategies mainly potential techniques, appropriate drug formulations, and new transport systems for quick, easy, and safe delivery of drugs across blood brain barrier to save the life of tumor and virus infected patients. PMID- 27355041 TI - An Examination of Forest Certification Status among Logging Companies in Cameroon. AB - This paper assesses the level of interest, awareness, and adoption of ISO 14001 and Forest Stewardship Council (FSC) certification schemes among logging companies in Cameroon. Eleven logging companies located in Douala in the Littoral Region of Cameroon were assessed through a structured interview using an administered questionnaire which was mostly analyzed qualitatively thereafter. The findings indicated that none of the companies was certified for ISO 14001; however 63.64% of them were already FSC-certified. Four companies (36.36%) were neither FSC- nor ISO 14001 EMS-certified. Among the factors found to influence the adoption rate was the level of awareness about ISO 14001 and FSC certification schemes. The main drivers for pursuing FSC certification were easy penetration into international markets, tax holiday benefits, and enhancement of corporate image of the logging companies through corporate social responsibility fulfillments. Poor domestic market for certified products was found to be the major impediment to get certified. To make logging activities more environmentally friendly and socially acceptable, logging companies should be encouraged to get certified through the ISO 14001 EMS scheme which is almost nonexistent so far. This requires awareness creation about the scheme, encouraging domestic markets for certified products and creating policy incentives. PMID- 27355042 TI - The Wind Energy Potential of Kurdistan, Iran. AB - In the current work by using statistical methods and available software, the wind energy assessment of prone regions for installation of wind turbines in, Qorveh, has been investigated. Information was obtained from weather stations of Baneh, Bijar, Zarina, Saqez, Sanandaj, Qorveh, and Marivan. The monthly average and maximum of wind speed were investigated between the years 2000-2010 and the related curves were drawn. The Golobad curve (direction and percentage of dominant wind and calm wind as monthly rate) between the years 1997-2000 was analyzed and drawn with plot software. The ten-minute speed (at 10, 30, and 60 m height) and direction (at 37.5 and 10 m height) wind data were collected from weather stations of Iranian new energy organization. The wind speed distribution during one year was evaluated by using Weibull probability density function (two parametrical), and the Weibull curve histograms were drawn by MATLAB software. According to the average wind speed of stations and technical specifications of the types of turbines, the suitable wind turbine for the station was selected. Finally, the Divandareh and Qorveh sites with favorable potential were considered for installation of wind turbines and construction of wind farms. PMID- 27355043 TI - Impact of Site Disturbances from Harvesting and Logging on Soil Physical Properties and Pinus kesiya Tree Growth. AB - A study was conducted to determine the impacts of soil disturbance and compaction on soil physical properties and tree growth and the effectiveness of tillage in maintaining or enhancing site productivity for intensively managed Pinus kesiya Royle ex Gordon sites in Dedza, Malawi. The results indicate that about fifty-two percent of the area of compacted plots was affected by the vehicular traffic. Seventy percent of the trees were planted on microsites with some degree of soil disturbance. Soil bulk density at 0-20 cm depth increased from 0.45 to 0.66 Mg m( 3) in the most compacted portions of traffic lanes. Soil strength in traffic lanes increased at all 60 cm depth but never exceeded 1200 kPa. Volumetric soil water content in compacted traffic lanes was greater than that in noncompacted soil. Total soil porosity decreased 13.8% to 16.1% with compaction, while available water holding capacity increased. The study revealed no detrimental effects on tree height and diameter from soil disturbance or compaction throughout the three growing season. At the ages of two and three, a tree volume index was actually greater for trees planted on traffic lanes than those on nondisturbed soil. PMID- 27355044 TI - Fekete-Szego Inequalities for Certain Classes of Biunivalent Functions. AB - We obtain the Fekete-Szego inequalities for the classes S S,Sigma (*)(alpha, phi) and L S,Sigma(alpha, phi) of biunivalent functions denoted by subordination. The results presented in this paper improve the recent work of Crisan (2013). PMID- 27355045 TI - A Study of Clinical, Microbiological, and Echocardiographic Profile of Patients of Infective Endocarditis. AB - Infective endocarditis, a great masquerader, is a clinical entity which may present with a myriad of manifestations. Its changing epidemiological profile has been studied in the previous decades in both the developed and the developing nations. In this study, we strived to uphold the evolving clinical profile and its outcome from a government tertiary care hospital in Northern India. It was a descriptive, cross-sectional, observational study conducted over two years' period involving 44 patients diagnosed with definite infective endocarditis, according to modified Dukes' criteria. Demographic, clinical, microbiological, and echocardiographic data were analysed. Mean age of patients was 31 years. Rheumatic heart disease with regurgitant lesions was the commonest risk factor. Dyspnea and fever were the predominant symptom, and pallor and heart failure the commonest sign. Cultures were positive in 52% with Staphylococcus, the major isolate. Transesophageal echocardiography fared better than transthoracic one to define the vegetations. Mortality is reported in 4.5%. Prolonged duration of fever, pallor, hematuria, proteinuria, rheumatoid factor positivity, and large vegetations proved to be poor prognostic variables. Culture positive endocarditis, with persistent bacteremia, had higher incidence of acute renal failure. Right sided endocarditis was frequent in congenital lesions or IV drug user, whereas left sided endocarditis mostly presented with atrial fibrillation. PMID- 27355046 TI - On Study of Immune Response to Tumor Cells in Prey-Predator System. AB - This paper aims to develop the mathematical model that explores the immune response to a tumor system as a prey-predator system. A deterministic model defining the dynamics of tumor growth progression and regression has been analyzed. Our analysis indicates the tumor recurring and dormancy on the cellular level in combination with resting and hunting cells. The model considered in the present study is a generalization of El-Gohary (2008) by introducing the Michaelis-Menten function. This function describes the stimulation process of the resting cells by the tumor cells in the presence of tumor specific antigens. Local and global stability analysis have been performed along with the numerical simulation to support our findings. PMID- 27355047 TI - Ophthalmic Manifestations of HIV Patients in a Rural Area of Western Maharashtra, India. AB - Introduction. HIV/AIDS is one of twenty first century's biggest global challenges to mankind with protean manifestations affecting all organs of our body, not even sparing the eyes. The purpose of this study was to determine the pattern of ocular manifestations of HIV/AIDS and their correlation with CD4-count in a rural area of India. Methods. A hospital based observational cross-sectional study was done on 40 HIV-positive patients presenting to ART center with ocular complaints. Data were collected using face-to-face interview, clinical examination, slit lamp examination, fundus examination, and laboratory investigations. Results. Out of 40 patients, 21 were males and 19 were females with mean age of 38.75 +/- 13.9 years. HIV retinopathy was the most common HIV-associated ophthalmic lesion while anterior uveitis was the most common anterior segment finding. Posterior segment lesions showed significant association (P < 0.05) with low CD4-count of the patient. CMV retinitis, retinal detachment, tubercular chorioretinitis, and acute retinal necrosis were all seen in patients with CD4-count less than 100 cells/mm(3). Conclusions. HIV retinopathy, CMV retinitis, herpes zoster ophthalmicus, and anterior uveitis are common ocular manifestations associated with HIV infection. Low CD4-count is a risk as well as predictor for ocular manifestations. There needs to be awareness of ocular involvement among HIV infected individuals and an increased emphasis on regular ophthalmic examination. PMID- 27355048 TI - Microplate Agglutination Test for Canine Brucellosis Using Recombinant Antigen Coated Beads. AB - Brucella canis, a facultative intracellular pathogen, is the causative agent of canine brucellosis. The diagnosis of canine brucellosis is based on bacteriological examination and serological methods, including agglutination and gel diffusion tests. In this study, four recombinant antigens, heat shock protein 60, rhizopine-binding protein, Cu-Zn superoxide dismutase, and hypothetical protein (Ag 4), were constructed. These antigens were coated on latex beads and their usefulness in the serological diagnosis of canine brucellosis was examined. All recombinant antigens showed specific reaction with sera from B. canis infected dogs in Western blotting. In a microplate agglutination test, mixing sera from B. canis-infected dogs, but not sera from B. canis-free dogs, with single or multiple antigens-coated latex beads produced clear agglutination. Moreover, the antigen-coated latex beads did not show nonspecific agglutination in hemolyzed serum samples. A survey of canine serum samples conducted by the microplate agglutination test using single antigen-coated latex beads showed that this method would be useful in the serological diagnosis of canine brucellosis. Further investigations using more serum samples are required to confirm the usefulness of our method. PMID- 27355049 TI - Prevalence of Orthodontic Treatment Need and Occlusal Traits in Schoolchildren. AB - Background. Widespread use of the IOTN along with detailed study of occlusal traits is suitable for planning community dental health resources. Objectives. The aim of current study was to assess the need for orthodontic treatment among school children of Tehran by means of the Dental Health Component (DHC) of the Index of Orthodontic Treatment Need (IOTN) and also to evaluate the occlusal traits of the subjects. Methods. 684 (343 boys and 341 girls) school children, 15 to 17 years of age, were selected at random from 12 schools to represent the four main areas of Tehran. The final sample who met the inclusion criteria comprised 643 subjects (322 males and 321 females). Malocclusion was determined with the Index of Orthodontic Treatment Need. The IOTN grades were statistically compared in the two genders using chi-square test. Results. Orthodontic treatment need, using the DHC, was found in only 9.0 per cent of the children. The prevalence of Angle Class I malocclusion in this study was higher than other malocclusions (65.2 per cent), followed by crowding in 62.7 per cent of the subjects. Conclusion. Orthodontic treatment need for Tehran high school students was relatively lower than that reported in most recent studies in Europe. PMID- 27355050 TI - Analysis of Unweighted Amino Acids Network. AB - The analysis of amino acids network is very important to studying the various physicochemical properties of amino acids. In this paper we consider the amino acid network based on mutation of the codons. To analyze the relative importance of the amino acids we have discussed different measures of centrality. The measure of centrality is a powerful tool of graph theory for ranking the vertices and analysis of biological network. We have also investigated the correlation coefficients between various measures of centrality. Also we have discussed clustering coefficient as well as average clustering coefficient of the network. Finally we have discussed the degree of distribution as well as skewness. PMID- 27355051 TI - Efficiency and Flexibility of Fingerprint Scheme Using Partial Encryption and Discrete Wavelet Transform to Verify User in Cloud Computing. AB - Now, the security of digital images is considered more and more essential and fingerprint plays the main role in the world of image. Furthermore, fingerprint recognition is a scheme of biometric verification that applies pattern recognition techniques depending on image of fingerprint individually. In the cloud environment, an adversary has the ability to intercept information and must be secured from eavesdroppers. Unluckily, encryption and decryption functions are slow and they are often hard. Fingerprint techniques required extra hardware and software; it is masqueraded by artificial gummy fingers (spoof attacks). Additionally, when a large number of users are being verified at the same time, the mechanism will become slow. In this paper, we employed each of the partial encryptions of user's fingerprint and discrete wavelet transform to obtain a new scheme of fingerprint verification. Moreover, our proposed scheme can overcome those problems; it does not require cost, reduces the computational supplies for huge volumes of fingerprint images, and resists well-known attacks. In addition, experimental results illustrate that our proposed scheme has a good performance of user's fingerprint verification. PMID- 27355052 TI - Intestinal Protozoal Parasites in Diarrheal Children and Associated Risk Factors at Yirgalem Hospital, Ethiopia: A Case-Control Study. AB - Aim. A case-control study was conducted to determine the prevalence of G. lamblia, Cryptosporidium, spp and E. histolytica/dispar in diarrheal children at Yirgalem Hospital from February 2011 to August. Subjects and Methods. A total of 230 children participated in the study of which 115 (50%) were cases and 115 (50%) were controls. A single stool sample was collected and examined by direct saline wet mount, formol-ether concentration, and modified Ziehl-Neelsen. Results. Eighty-four (36.52%) were positive for at least one intestinal parasites (57 (49.56%) from diarrheal children and 27 (23.47%) out of nondiarrheal children). The prevalence of G. lamblia, Cryptosporidium spp, and E. histolytica/dispar was 15.65%, 9.56%, and 4.35% in children with diarrhea and 1.74%, 5.21%, and 1.74% in those without it, respectively. Cryptosporidium spp and E. histolytica/dispar revealed higher infection in males (10.81% and 5.4%, resp.) than in females (7.32% and 2.43%, resp.). G. lamblia infection was higher in females (29.27%) than in males (8.11%). Cryptosporidium spp infection was higher in the age groups of <=4 years old (53.84%). Significant difference was seen between 10 and 13 (7.69%) years old. Higher prevalence of E. histolytica/dispar was found in 5-9 years (85.71%) than <=4 years old (14.28%). Conclusion. Cryptosporidium spp, E. histolytica/dispar, and G. lamblia were higher in children with diarrhea than in those without it. PMID- 27355053 TI - Intuitionistic Fuzzy Weighted Linear Regression Model with Fuzzy Entropy under Linear Restrictions. AB - In fuzzy set theory, it is well known that a triangular fuzzy number can be uniquely determined through its position and entropies. In the present communication, we extend this concept on triangular intuitionistic fuzzy number for its one-to-one correspondence with its position and entropies. Using the concept of fuzzy entropy the estimators of the intuitionistic fuzzy regression coefficients have been estimated in the unrestricted regression model. An intuitionistic fuzzy weighted linear regression (IFWLR) model with some restrictions in the form of prior information has been considered. Further, the estimators of regression coefficients have been obtained with the help of fuzzy entropy for the restricted/unrestricted IFWLR model by assigning some weights in the distance function. PMID- 27355055 TI - Beneficial Effects of Maprotiline in a Murine Model of Colitis in Normal and Reserpinised Depressed Rats. AB - Background. Anti-inflammatory and immunomodulatory activities have been reported for maprotiline, a strong norepinephrine reuptake inhibitor. In addition, some other antidepressant drugs have shown beneficial effects in experimental colitis. Methods. All the animals were divided into normal and depressed groups. In normal rats colitis was induced by instillation of 2 mL of 4% acetic acid and after 2 hours, maprotiline (10, 20, and 40 mg/kg, i.p.) was administered. In reserpinised depressed rats, depression was induced by injection of reserpine (6 mg/kg, i.p.), 1 h prior to colitis induction, and then treated with maprotiline (10, 20, and 40 mg/kg). Treatment continued daily for four days. Dexamethasone (1 mg/kg, i.p.) was given as a reference drug. On day five following colitis induction, animals were euthanized and distal colons were assessed macroscopically, histologically, and biochemically (assessment of myeloperoxidase activity). Results. Maprotiline significantly improved macroscopic and histologic scores and diminished myeloperoxidase activity in both normal and depressed rats while reserpine exacerbated the colonic damage. Conclusion. Our data suggests that the salutary effects of maprotiline on acetic acid colitis are probably mediated first through depressive behavioral changes that could be mediated through the brain-gut axis and second for the anti-inflammatory effect of the drug. PMID- 27355057 TI - Generic Submanifolds of Nearly Kaehler Manifolds with Certain Parallel Canonical Structure. AB - The class of generic submanifold includes all real hypersurfaces, complex submanifolds, totally real submanifolds, and CR-submanifolds. In this paper we initiate the study of generic submanifolds in a nearly Kaehler manifold from differential geometric point of view. Some fundamental results in this paper will be obtained. PMID- 27355054 TI - Bacteria in Nanoparticle Synthesis: Current Status and Future Prospects. AB - Microbial metal reduction can be a strategy for remediation of metal contaminations and wastes. Bacteria are capable of mobilization and immobilization of metals and in some cases, the bacteria which can reduce metal ions show the ability to precipitate metals at nanometer scale. Biosynthesis of nanoparticles (NPs) using bacteria has emerged as rapidly developing research area in green nanotechnology across the globe with various biological entities being employed in synthesis of NPs constantly forming an impute alternative for conventional chemical and physical methods. Optimization of the processes can result in synthesis of NPs with desired morphologies and controlled sizes, fast and clean. The aim of this review is, therefore, to make a reflection on the current state and future prospects and especially the possibilities and limitations of the above mentioned bio-based technique for industries. PMID- 27355056 TI - Impact of Comorbidity, Race, and Marital Status in Men Referred for Prostate Biopsy with PSA >20 ng/mL: A Pilot Study in High-Risk Patients. AB - Objective. To assess the impact of comorbidity, race, and marital status on overall survival (OS) among men presenting for prostate biopsy with PSA >20 ng/mL. Methods. Data were reviewed from 2000 to 2012 and 78 patients were included in the cohort. We analyzed predictors of OS using a Cox proportional hazards model and the association between Charlson Comorbidity Index (CCI) score and PCa diagnosis or high-grade cancer using logistic regression and multinomial regression models, respectively. Results. The median age of patients was 62.5 (IQR 57-73) years. Median CCI was 3 (IQR 2-4), 69% of patients were African American men, 56% of patients were married, and 85% of patients had a positive biopsy. CCI (HR 1.52, 95% CI 1.19, 1.94), PSA (HR 1.62, 95% CI 1.09, 2.42), and Gleason sum (HR 2.04, 95% CI 1.17, 3.56) were associated with OS. CCI was associated with Gleason sum 7 (OR 4.06, 95% CI 1.04, 15.89) and Gleason sum 8-10 (OR 4.52, 95% CI 1.16, 17.54) PCa. Conclusions. CCI is an independent predictor of high-grade disease and worse OS among men with PCa. Race and marital status were not significantly associated with survival in this cohort. Patient comorbidity is an important component of determining the optimal approach to management of prostate cancer. PMID- 27355058 TI - A GPU-Based Gibbs Sampler for a Unidimensional IRT Model. AB - Item response theory (IRT) is a popular approach used for addressing large-scale statistical problems in psychometrics as well as in other fields. The fully Bayesian approach for estimating IRT models is usually memory and computationally expensive due to the large number of iterations. This limits the use of the procedure in many applications. In an effort to overcome such restraint, previous studies focused on utilizing the message passing interface (MPI) in a distributed memory-based Linux cluster to achieve certain speedups. However, given the high data dependencies in a single Markov chain for IRT models, the communication overhead rapidly grows as the number of cluster nodes increases. This makes it difficult to further improve the performance under such a parallel framework. This study aims to tackle the problem using massive core-based graphic processing units (GPU), which is practical, cost-effective, and convenient in actual applications. The performance comparisons among serial CPU, MPI, and compute unified device architecture (CUDA) programs demonstrate that the CUDA GPU approach has many advantages over the CPU-based approach and therefore is preferred. PMID- 27355059 TI - Effects and Management of Parthenium hysterophorus: A Weed of Global Significance. AB - Congress grass, Parthenium hysterophorus L., of the family Asteraceae (tribe: Heliantheae), is an erect and much branched annual or ephermeral herb, known for its notorious role as environmental, medical, and agricultural hazards. It is believed to have been introduced into India and Australia from North America and in the last few years the weed has emerged as the seventh most devastating weed in Africa, Asia, and Australia. The aim of this review is to provide general information about the physiology, distribution, ill effects, and management of parthenium. Control of parthenium has been tried by various methods, but no single management option would be adequate to manage parthenium, and there is a need to integrate various management options. Successful management of this weed can only be achieved by an integrated approach with biological control as the key element. PMID- 27355060 TI - Effect of Strontium Chloride on Experimental Bladder Inflammation in Rat. AB - Introduction. Strontium salts are anti-irritants for chemically induced sensory irritation. Interstitial cystitis is a painful disease without definitive therapy. The aim of the study was to determine the effect of strontium in bladder with experimental interstitial cystitis model. Material and Methods. Rats' bladders in control group were instilled with NaCl. Second group was instilled with E. coli LPS. Third group was instilled with strontium. Fourth group was initially instilled with strontium and then LPS. Fifth group was instilled with LPS initially and then strontium. Urine of rats was collected at the beginning and end of the study. Results. Histamine and TNF-alpha changes were statistically significant in the second group but were not significant in the third group. When we compared the histamine levels of second via fourth and fifth groups the changes were statistically not significant. When we compared the TNF-alpha levels of second via fourth and fifth groups the changes were statistically significant. Conclusions. In our model, strontium did not make any significant changes in histopathology or histamine levels; however, it significantly reduced the levels of TNF-alpha. Given the role of TNF-alpha in the physiopathology of interstitial cystitis, these results suggested that further studies are required to evaluate the potential use of strontium in the management of interstitial cystitis. PMID- 27355061 TI - Facile Synthesis, Characterization, and In Vitro Antimicrobial and Anticancer Activities of Biscoumarin Copolyester Bearing Pendant 3-(Trifluoromethyl)Styrene. AB - Synthesis of random biscoumarin copolyester bearing pendant 3 (trifluoromethyl)styrene was prepared by the reaction of biscoumarin monomer 3 and hydroquinone 5 with azeloyl chloride. The influence of pendant 3 (trifluoromethyl)styrene unit on the properties of copolyester such as inherent viscosity, solubility, and thermal stability was investigated and compared in detail. The inherent viscosity and polydispersity index of the copolyester were found to be 0.15 dL/g and 1.36, respectively. The chemical structure of the copolyester was investigated by Fourier-transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance ((1)H-NMR) spectroscopy. The physical properties of copolyester were characterized by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), gel permeation chromatography (GPC), and X-ray diffraction (XRD) technique. Agar disc diffusion method was employed to study the antimicrobial activity of the random copolyester. In vitro anticancer activity against lung cancer (Hep-2) cell line was also investigated. PMID- 27355062 TI - Existence of Multiple Solutions for a Quasilinear Biharmonic Equation. AB - Using three critical points theorems, we prove the existence of at least three solutions for a quasilinear biharmonic equation. PMID- 27355063 TI - The Incidence of Impacted Maxillary Canines in a Kosovar Population. AB - Aim. The purpose of this study was to investigate the incidence of impacted maxillary canines in a Kosovar population. Materials and Methods. The study consisted of a retrospective analysis of the records of 8101 patients treated in the University Dentistry Clinical Center of Kosovo between August 2001 and February 2004. The chi-squared test was used to examine potential differences in the distribution of impacted maxillary canines stratified by gender, age, location (left or right), and position. P < 0.05 was accepted as statistically significant. Results. It was found that the incidence of impacted maxillary canines was 1.62%. Of the 131 impacted maxillary canines, 101 were in female patients and 30 were in male patients, a statistically significant difference. Ages were in the range of 9 to >20 years, with a mean age of 24.38 +/- 8.09 years. Of these subjects, 99 (75.57%) had unilaterally impacted maxillary canines, while 32 (24.43%) had bilateral impactions, a statistically significant difference (P < 0.00002). Impacted canines in 92 subjects (70.2%) were palatally placed, and 18 (13.7%) were labially placed. This difference was also statistically significant (P < 0.00001). Conclusion. The incidence of impacted maxillary canines in the sample Kosovar population was 1.62%, which is comparable to the findings from previous studies. PMID- 27355064 TI - Locking Compression Plate in Distal Femoral Intra-Articular Fractures: Our Experience. AB - Background. Intra-articular fractures of distal femur present a huge surgical challenge. The aim of this study is to evaluate functional outcome, fracture healing, and the complications of distal femoral intra-articular fractures using locking compression plates. Material and Methods. We reviewed 46 distal femoral fractures treated with distal femoral locking compression plates between 2009 to 2012. There were 36 men and 10 women with mean age of 35 years (range 20-72). More than half of the patients were of type C3 (AO classification) and had been caused by high energy trauma with associated injuries. Results. 2 patients were lost to follow-up. Of the remaining 44 patients, the mean follow-up period was 25 months (range 18-36). The mean time for radiological union was 12 weeks (range 10 18) except 2 patients which had gone for nonunion. At the latest follow up ROM >120 degrees is noted in 32 patients, 90-120 in 10 patients, and 70-90 in 2 patients. 38 patients (86%) had good/excellent outcome. Conclusion. Use of standard lateral approach for simple intra-articular distal femoral fractures (C1) and transarticular/minimally invasive techniques for complex intra-articular fractures (C2/C3) results in improved exposure of the knee joint and better union rates with low incidence of bone grafting. PMID- 27355065 TI - Predictors of Salivary Fistulas in Patients Undergoing Salvage Total Laryngectomy. AB - Background. Salivary fistula is a common complication after salvage total laryngectomy. Previous studies have not considered the number of layers of pharyngeal closure and have not classified fistulas according to severity. Our objective was to analyze our institutional experience with salvage total laryngectomy, categorize salivary fistulas based on severity, and study the effect of various pharyngeal closure techniques on fistula incidence. Methods. Retrospective analysis of 48 patients who underwent salvage total laryngectomy, comparing pharyngeal closure technique and use of a pectoralis major flap with regard to salivary fistula rate. Fistulas were categorized into major and minor fistulas based on whether operative intervention was required. Results. The major fistula rate was 18.8% (9/48) and the minor fistula rate was 29.2% (14/48). The overall (major plus minor) fistula rate was 47.9%. The overall fistula and major fistula rates decreased with increasing the number of closure layers and with use of a pectoralis major flap; however, these correlations did not reach statistical significance. Other than age, there were no clinicopathologic variables associated with salivary fistulas. Conclusion. For salvage total laryngectomies, increasing the number of closure layers or use of a pectoralis major flap may reduce the risk of salivary fistula. PMID- 27355066 TI - Coefficient Estimates for New Subclasses of Meromorphic Bi-Univalent Functions. AB - We introduce and investigate two new subclasses M sigma (alpha, lambda) and M sigma (beta, lambda) of meromorphic bi-univalent functions defined on Delta = {z : z ? C, 1 < |z | 0.05). Conclusions. 0.1% and 0.2% nanosilver gel is more effective on Enterococcus faecalis biofilm as compared to chlorhexidine gluconate and camphorated phenol. PMID- 27355069 TI - Parasitic Contamination of Fruits and Vegetables Collected from Selected Local Markets of Jimma Town, Southwest Ethiopia. AB - Background. A study aimed at determining the prevalence and predictors of parasitic contamination of fruits and vegetables collected from local markets in Jimma Town, Ethiopia, was conducted between April and May 2013. Methods. A total of 360 samples of fruits and vegetables were examined by sedimentation concentration after washing using normal saline. Results. The overall prevalence of parasitic contamination was 57.8%. Strongyloides like parasite (21.9%) was the most frequent parasitic contaminant followed by Toxocara Spp (14.7%), Cryptosporidium Spp (12.8%), H. nana (8.3%), G. lamblia (7.5%), A. lumbricoides (6.7%), E. histolytica/dispar (5.3%), Cyclospora spp (5.0%), and H. diminuta (1.4%). Washing of the fruits and vegetables before display for selling was significantly associated with decreased parasitic contamination (P < 0.001). Conclusion. Since fruits and vegetables are potential sources of transmission for intestinal parasites in the study area, consumers should always avoid acquiring parasitic infection from contaminated fruits and vegetables supplied in Jimma Town through proper cleaning and cooking. PMID- 27355068 TI - Attitudes and Practices of Surgeons towards Spilled Gallstones during Laparoscopic Cholecystectomy: An Observational Study. AB - The sequelae of spilled gallstones after Laparoscopic cholecystectomy (LC) and the occurring complications may go unnoticed for a long time and can be a diagnostic challenge. The aim of this survey was to study the knowledge, attitude, and practices of surgeons regarding spilled gallstones during LC. An observational, cross-sectional survey, using a questionnaire based on 11 self answered close-ended questions, was conducted among general surgeons. Of the 138 respondents only 29.7% had observed a complication related to gallstone spillage during LC. There was varied opinion of surgeons regarding management of spilled gallstones, documenting the same in operative notes and consent. It was observed that there is lack of knowledge regarding the complications related to gallstone spillage during LC. There is need to educate surgeons regarding safe practices during LC to avoid gallstone spillage, early diagnosis, and management of complications. There is need to standardize practice to retrieve lost gallstones to reduce complication and legal consequences. PMID- 27355070 TI - Does a Dedicated Unit for the Treatment of Hip Fractures Improve Acute Outcomes? AB - The aim of this study is to establish whether management of patients in a unit dedicated to the treatment of hip fractures improves acute outcomes. We prospectively studied 300 patients with hip fractures in two separate groups. Patients in Group 1 were operated on in a mixed trauma unit and recovered in a traditional trauma ward. Patients in Group 2 were operated on in dedicated theatres and recovered in a unit which catered exclusively for hip fractures. The ages, ASA grades, and type of procedure performed in the two groups were comparable. The 30-day mortality rate in Group 2 was 9% as opposed to 12% in Group 1 (P = 0.34). The inpatient length of stay was significantly lower in Group 2 (18 days versus 25 days; P = 0.0002) and so was the time taken to operate (28 hours versus 34 hours; P = 0.04). A greater percentage of patients in Group 2 were discharged home as opposed to a nursing home (75% versus 67%). This difference approached significance (P = 0.18). We conclude that prioritisation and prompt management of patients with hip fractures in a dedicated unit significantly improve time to surgery and significantly decrease length of stay. PMID- 27355072 TI - Hepatitis B Infection Awareness among Dental Graduate Students: A Cross Sectional Study. AB - Hepatitis B virus transmission in a dental setting more commonly occurs due to inadequate/improper use of safety measures by the dentist. This particular study evaluated the hepatitis B virus infection related awareness among dental graduate students in a University Dental College, India. A validated questionnaire regarding the awareness about hepatitis infection and various infection control measures was distributed among the students of different year of study in undergraduate bachelor dental graduate program. The data extracted were tabulated and analyzed. Final year students showed an increased awareness when compared to third year students. There is need for improving the knowledge among the nonclinical students, mainly on transmission of virus through salivary contact. The overall awareness among the students is only fairly satisfying, which signifies the need for continued infection control education among the students. PMID- 27355073 TI - The Fate of Patients Who Started Hemodialysis during Childhood or Adolescence: Results of an Interregional Moroccan Survey. AB - Hemodialysis is the most used renal replacement therapy for children in Morocco. The objective of this study was to determine the prevalence of patients who started hemodialysis in childhood and study their characteristics and specificities of their care. For this we conducted a multicentric descriptive cross-sectional study of all chronic hemodialysis patients who started dialysis in pediatric age, in hemodialysis centers in four of the sixteen regions of Morocco. We collected 2066 patients undergoing dialysis in 39 hemodialysis centers; from these, only 72 patients (3.48%) started hemodialysis in childhood. The average age of patients was 20.64 +/- 6.5 years with a sex ratio of 1.9. Duration of dialysis was 78.2 +/- 56 months. The cause of end stage renal disease was urological abnormalities in 18% of cases and glomerulopathy in 12.5% of cases; however, it remains unknown in half of the patients. Over 18 years, 74% of patients are without profession, it is active in 13% of cases, and pursuing studies are only in 13% of cases. Patients under 5 years and those with a low weight are rarely taken care of in chronic hemodialysis with little individualization of prescription. Greater attention should be paid to renal transplantation that is desired by the majority of these patients (92%). PMID- 27355074 TI - Determinant Factors of Anemia among Nonpregnant Women of Childbearing Age in Southwest Ethiopia: A Community Based Study. AB - Background. Anemia affects one-quarter of the world's population; nonpregnant women were one of the groups for whom it is common, making it a global public health problem. Objective. To determine prevalence and risk factors of anemia among nonpregnant women of childbearing age in Jimma town southwest Ethiopia. Methodology. We conducted a community based cross-sectional study involving 441 nonpregnant women. Data was collected over two months of period. We collected sociodemographic and related data using structured questionnaire. We collected four milliliters of venous blood and five grams of stool samples from each study participant for hematological and parasitological analysis. We performed statistical analysis using SPSS-V 16 software. Result. The prevalence of anemia was 16.1% (n = 71) with mean hemoglobin 12.96 g/dL (+/-1.04), among which 97.2% (n = 69) were mildly anemic. Age group of 25-36 years old, lower economic level, illiteracy, multiparity, having intestinal parasitic infection, using more than two sanitary pads per day during menstruation period, and low body mass index were found to be risk factors of anemia among the group. Conclusion. Prevalence of anemia indicates mild public health importance which shows it was indeed public health problem. Identified risk factors should be considered for prevention and control of anemia among the group. PMID- 27355071 TI - Ethnopharmacological Significance of Eclipta alba (L.) Hassk. (Asteraceae). AB - Eclipta alba can be found growing wild in fallow lands of Bangladesh where it is considered as a weed by farmers. Traditional medicinal systems of the Indian subcontinent countries as well as tribal practitioners consider the plant to have diverse medicinal values and use it commonly for treatment of gastrointestinal disorders, respiratory tract disorders (including asthma), fever, hair loss and graying of hair, liver disorders (including jaundice), skin disorders, spleen enlargement, and cuts and wounds. The plant has several phytoconstituents like wedelolactone, eclalbasaponins, ursolic acid, oleanolic acid, luteolin, and apigenin. Pharmacological activities of plant extracts and individual phytoconstituents have revealed anticancer, hepatoprotective, snake venom neutralizing, anti-inflammatory, and antimicrobial properties. Phytoconstituents like wedelolactone and ursolic and oleanolic acids as well as luteolin and apigenin can form the basis of new drugs against cancer, arthritis, gastrointestinal disorders, skin diseases, and liver disorders. PMID- 27355076 TI - Finite Buffer GI/M(n)/1 Queue with Bernoulli-Schedule Vacation Interruption under N-Policy. AB - We study a finite buffer N-policy GI/M(n)/1 queue with Bernoulli-schedule vacation interruption. The server works with a slower rate during vacation period. At a service completion epoch during working vacation, if there are at least N customers present in the queue, the server interrupts vacation and otherwise continues the vacation. Using the supplementary variable technique and recursive method, we obtain the steady state system length distributions at prearrival and arbitrary epochs. Some special cases of the model, various performance measures, and cost analysis are discussed. Finally, parameter effect on the performance measures of the model is presented through numerical computations. PMID- 27355075 TI - In Vitro and In Vivo Biochemical Evaluations of the Methanolic Leaf Extract of Garcinia kola. AB - Garcinia kola Heckel (Guttiferae) leaves have received limited scientific attention despite their traditionally acclaimed medicinal properties. The scavenging ability of the methanolic leaf extract (MLE) of G. kola was assayed for hydroxyl radical (OH(*)), superoxide anion (O2 (-)), 1,1-diphenyl-2 picrylhydrazyl (DPPH), azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS(*+)), and lipid peroxidation (LP) activity in egg yolk, rat liver, and brain homogenates. Total phenolic and flavonoid contents of the extract were also evaluated. Group I animals were given oral doses of water, whereas Group II and Group III animals received 100 and 200 mg/kg body weight (bw) MLE, respectively, for 14 days. Plasma glucose, magnesium, gamma-glutamyltransferase (GGT/gammaGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and urea were evaluated. Hepatic reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), LP, and liver histopathological appearance were also assessed. The extract scavenged OH(*), O2 (-), DPPH, and ABTS(*+) and inhibited LP in egg yolk, rat liver, and brain homogenates. Furthermore, oral administration of the extract showed no adverse effects on hepatic and renal function tests. Increased hepatic GSH and nonsignificant changes in LP, GPx and SOD activities, and liver histology were observed. These results suggest that G. kola leaves have antioxidant activities which may have application in traditional medicine. PMID- 27355077 TI - Knowledge, Attitude, and Practice regarding Food, and Waterborne Outbreak after Massive Diarrhea Outbreak in Yazd Province, Iran, Summer 2013. AB - Objective. This Study was conducted after a diarrhea outbreak that occurred in Yazd Province, Iran. The aim of the study was to compare knowledge, attitude, practice, and other risk factors of the affected communities regarding diarrhea outbreak (the cities of Zarch, Meybod, and Ardakan) to nonaffected communities (the cities of Yazd and Taft). Methods. A knowledge, attitude, and practice (KAP) survey study was conducted from August to September 2013 enrolling 505 subjects who were referred to health centers anonymously during the epidemic. The questionnaire included the following four parts: (a) general characteristics such as gender, education level, source of health information obtaining; (b) 12 questions on knowledge (Min = 0, Max = 36); (c) 10 questions on attitude (Min = 0, Max = 50); and (d) nine questions on practice (Min = 0, Max = 27). Results. The overall mean score of knowledge, attitude, and practice was 28.17 (SD = 4.58), 37.07 (SD = 4.39), and 21.31 (SD = 3.81), respectively. Practice on food- and waterborne outbreaks was significantly higher in females (P = 0.001) and in nonaffected communities (P = 0.031). Conclusions. Nonaffected communities had a considerably better practice score. With the increase in the score of knowledge about food- and waterborne outbreaks, the score of practice increased slightly. PMID- 27355079 TI - Assessing Child Maltreatment in Children Born to Mothers Who Used Methamphetamine during Pregnancy at Siriraj Hospital, Bangkok, Thailand: A Pilot Study. AB - Studies on maltreatment of children born to methamphetamine abusing mothers are lacking. This cross-sectional study examined child maltreatment among children born at Siriraj Hospital, Bangkok, Thailand, to mothers who used methamphetamines during pregnancy. During the study period between July 2011 and January 2012, 34 caretakers of these children were interviewed using the ISPCAN Child Abuse Screening Tool-Parent Version (ICAST-P) to assess their disciplinary actions. The associations between child's and caretaker's characteristics and child maltreatment behaviors were analyzed. More than 90% of caretakers were female with age ranging from 18 to 35 years and about 60% were biological mothers. The children's age ranged from 1 to 9 years. Disciplinary acts and child rearing practices that were considered to be child maltreatment behaviors were reported as follows: psychological discipline 82.4%, physical discipline 79.4%, and neglect 29.4%. No associations between the child's or the caretaker's characteristics and child maltreatment behaviors were found. In conclusion, child maltreatment behaviors were frequent in caretakers of children born to mothers who used methamphetamine during pregnancy. Supervision on child rearing and careful monitoring are needed for this population. PMID- 27355078 TI - Incidence of Radix Entomolaris in Mandibular First Molars in Palestinian Population: A Clinical Investigation. AB - Purpose. The aim of this investigation was to evaluate clinically the percentage of permanent mandibular first molar teeth with three roots amongst Palestinian population. Patients and Methods. Three hundred twenty-two mandibular first molars from 185 females and 137 males scheduled for root canal treatment at the Dental Center of the Arab American University were examined over a 2-year period. The incidence of a third root revealed by periapical radiographs and the comparison of the occurrence between males and females and between the right and left sides of the mandible were recorded. Statistical Analysis. It was performed using the chi-square test with a significant level set at P < 0.05%. Results. Of the 322 treated mandibular first molars, twelve teeth were found to have a third root with an overall incidence being 3.73%. More teeth with a third root were treated on the right side of the mandible compared to the left side. Conclusion. The incidence of a third root in Palestinian population was within the range of previous reports from the Middle East but considerably lower than the percentage from the Far East. PMID- 27355080 TI - Effect of 82% Lactic Acid in Treatment of Melasma. AB - Melasma is an acquired, chronic, and symmetrical hypermelanosis, characterized by brown patches of variable darkness on sun exposed areas of body. There are numerous modalities of treatment currently in use for this disease, of which the chemical peeling is very commonly used. Therefore, the present work was done to see the effect of 82% lactic acid peel in the treatment of melasma. A total number of 20 patients of either sex attending the OPD of dermatology department with clinically evident melasma were included in the study. 82% Lactic acid peel was applied on the face for 12 weeks in each patient. Patients were evaluated clinically and photographically at various intervals and in follow-up till 24 weeks. Assessment of patient satisfaction and side effects were also noted. All the subjects completed the study. Application of this peel for 12 weeks significantly decreased the melasma area severity index score and also melasma severity scale score. Patient and physician analogue scales also showed the improvement by the treatment. Regarding the adverse effects, burning sensation was the only side effect noted in our study. In conclusion, 82% lactic acid peel is well tolerated and can be used for the treatment of melasma. PMID- 27355081 TI - Stability Analysis of an Improved HBV Model with CTL Immune Response. AB - To better understand the dynamics of the hepatitis B virus (HBV) infection, we introduce an improved HBV model with standard incidence function, cytotoxic T lymphocytes (CTL) immune response, and take into account the effect of the export of precursor CTL cells from the thymus and the role of cytolytic and noncytolytic mechanisms. The local stability of the disease-free equilibrium and the chronic infection equilibrium is obtained via characteristic equations. Furthermore, the global stability of both equilibria is established by using two techniques, the direct Lyapunov method for the disease-free equilibrium and the geometrical approach for the chronic infection equilibrium. PMID- 27355082 TI - Determination of Magnesium Valproate and Its Process Related Impurities by Ultraperformance Liquid Chromatography. AB - A selective ultraperformance liquid chromatographic (UPLC) method for the determination of magnesium valproate and its process related impurities has been developed. The method includes reversed-phase Acquity BEH C18 column with 100 mm * 2.1 mm i.d. and 1.7 u particle size. The mobile phase consists of acetonitrile and 5 mM ammonium dihydrogen orthophosphate with pH = 3.0 at 45 : 55 isocratic elution. The flow rate was set at 0.3 mL/min and UV detection was performed at 215 nm. A system suitability test (SST) was developed to govern the quality of the separation. The developed method has been validated further with respect to linearity, accuracy, precision, selectivity, LOD, LOQ, and robustness. Different batches of samples were examined using this method; the method proved to be successful when applied to analyze a marketed magnesium valproate formulation. PMID- 27355083 TI - Canonical PSO Based K-Means Clustering Approach for Real Datasets. AB - "Clustering" the significance and application of this technique is spread over various fields. Clustering is an unsupervised process in data mining, that is why the proper evaluation of the results and measuring the compactness and separability of the clusters are important issues. The procedure of evaluating the results of a clustering algorithm is known as cluster validity measure. Different types of indexes are used to solve different types of problems and indices selection depends on the kind of available data. This paper first proposes Canonical PSO based K-means clustering algorithm and also analyses some important clustering indices (intercluster, intracluster) and then evaluates the effects of those indices on real-time air pollution database, wholesale customer, wine, and vehicle datasets using typical K-means, Canonical PSO based K-means, simple PSO based K-means, DBSCAN, and Hierarchical clustering algorithms. This paper also describes the nature of the clusters and finally compares the performances of these clustering algorithms according to the validity assessment. It also defines which algorithm will be more desirable among all these algorithms to make proper compact clusters on this particular real life datasets. It actually deals with the behaviour of these clustering algorithms with respect to validation indexes and represents their results of evaluation in terms of mathematical and graphical forms. PMID- 27355084 TI - Adolescent idiopathic scoliosis: current concepts on neurological and muscular etiologies. AB - Adolescent idiopathic scoliosis (AIS) is a frequent disease but its etiology remains unknown. Gender prevalence in females is already known and there are many suggested hypotheses to explain its origin and manifestation, like associated neurologic, muscular and connective tissue disorders. Literature reports have tried to analyze disease prevalence in selected populations, possible ways of inheritance, related genes location and their polymorphisms, which may play a role in the development of the deformity. The purpose of this paper is to review and update concepts on the origin and genetic influence on AIS. PMID- 27355085 TI - "Clinical triad" findings in pediatric Klippel-Feil patients. AB - BACKGROUND: It has been propagated that patients with Klippel-Feil syndrome (KFS) exhibit "clinical triad" findings (CTFs), known as a short neck, low posterior hairline, and limited cervical range of motion (ROM). However, the literature has noted that up to 50 % of KFS cases may not present with such findings and the reasoning behind such assertions remains speculative. As such, the following study addressed the association between CTFs to that of congenitally-fused cervical segments and other risk factors in KFS patients. METHODS: We conducted a retrospective clinical study based on prospectively collected radiographic data. Thirty-one KFS patients at a single institution were assessed. Radiographs were used to evaluate the location and extent of congenitally-fused segments (spanning the occiput (O) to the first thoracic vertebra (T1)), as well as examining coronal and sagittal cervical alignments based on the Samartzis et al. KFS classification. Clinical records were evaluated to account for the initial clinical assessment of CTFs. Patients were further stratified into two groups: Group 1 included patients noted to have any CTFs, while Group 2 included patients who had no such findings. RESULTS: There were 12 males and 19 females (mean age at initial consultation: 9.7 years). No evidence of any of the CTFs was shown in 35.5 % of patients, whereas 38.7, 16.2 and 9.7 % were determined to have one, two or all three criteria, respectively. Limited cervical ROM was the most common finding (64.5 % of patients). In Group 1, 25 % had a short neck, 30 % a low posterior hairline, and 100 % exhibited limited cervical ROM. Group 1 had a mean of 3.9 fused cervical segments, whereas Group 2 had a mean of 2.5 fused cervical segments (p = 0.028). Age, sex-type, occipitalization and alignment parameters did not significantly differ to Group-type (p > 0.05). In Group 1, based on the Samartzis et al. Types I, II, and III, 16.7, 73.3, and 80.0 % of the patients, respectively, had at least one CTF. CONCLUSIONS: Complete CTFs were not highly associated during the clinical assessment of young KFS patients. However, KFS patients with extensive, congenitally-fused segments (i.e. Samartzis et al. Type III) were significantly more likely to exhibit one of the components of the CTF, which was predominantly a limited cervical ROM. Clinicians managing young pediatric patients should not rely on the full spectrum of CTFs and should maintain a high-index of suspicion for KFS, in particular in individuals that exhibit associated spinal findings, such as congenital scoliosis. PMID- 27355086 TI - Short term stroke outcome is worse among indiv1iduals with sickle cell trait. AB - BACKGROUND: Most (86%) of the global stroke mortality are from low- and middle income countries (LMIC) including African countries which have the highest prevalence of the sickle cell trait (Hb AS). The effects of this trait on stroke occurrence and outcome are poorly understood. We aimed to investigate the effects of the sickle cell trait on the 30-day stroke mortality in Nigerian-Africans. METHOD: This was a prospective study of 35 stroke patients with sickle cell trait (Haemoglobin AS) and 35 age and sex-matched controls without haemoglobinopathy (Haemoglobin AA). Haemoglobin electrophoresis was performed for all before recruitment and they all had neuroimaging done. Patients with haemoglobin AS were used as cases and those with haemoglobin AA as controls. The National Institute of Health Stroke Scale (NIHSS) was used to assess the severity of stroke at presentation and the Modified Rankin Scale for 30-day stroke outcome. RESULT: There was no significant difference in the baseline stroke severity between the two groups (p = 0.21). Univariate analysis of the factors predicting the 30-day stroke outcome revealed that NIHSS score > 20 (p < 0.001), haemorrhagic stroke (p = 0.01) and the presence of Hb AS (p < 0.001) were significantly associated with 30-day mortality. Haemorrhagic stroke type was strongly associated with HbAS (OR = 2.9, 95% CI = 1.10-7.99, p-value = 0.02). With multiple logistic regression model, the presence of Hb AS (p = 0.01) and NIHSS score > 20 (p = 0.05) emerged as independent risk factors for 30-day mortality. The cases had worse stroke outcome at 30 days. CONCLUSION: Stroke had1 a worse 30-day mortality and outcome in patients with sickle cell trait (HbAS) than in patients with normal adult haemoglobin (HbAA). PMID- 27355087 TI - Can Intestinal Fatty Acid Binding Protein (I-FABP) Be A Marker in the Diagnosis of Abdominal Pathology? AB - OBJECTIVES: Biochemical markers play an important role in the early diagnosis of abdominal pain. This study aimed to investigate the diagnostic value of intestinal type fatty acid binding protein (I-FABP) in patients with abdominal pathology. METHODS: This prospective and descriptive study was performed at the University Hospital Emergency Department. Serum I-FABP levels of patients presenting with acute abdominal pain were measured at time of admission and were compared with those of healthy individuals. RESULTS: The mean I-FABP level of the 171 patients enrolled in this study was 170.1+/-543.4 pg/ml, while that of a healthy control group was 61.4+/-47.4 pg/ml. Although I-FABP levels were higher in the patient group, this difference was not statistically significant (p>0.05). However, I-FABP levels of patients with mesenteric ischemia and intra-abdominal mass were significantly higher than those of healthy individuals (p<=0.05). CONCLUSIONS: I-FABP levels that are evaluated at time of admission in patients presenting with abdominal pain to the emergency department are significantly higher in patients with mesenteric ischemia and intra-abdominal mass than are those of healthy individuals. PMID- 27355088 TI - Rapid Intravenous Rehydration to Correct Dehydration and Resolve Vomiting in Children with Acute Gastroenteritis. AB - OBJECTIVES: The objective of this study is to evaluate the effect of rapid intravenous rehydration to resolve vomiting in children with acute gastroenteritis. METHODS: This randomized control trial was conducted in the pediatric emergency department in a tertiary care center in Tabriz, North-West of Iran. The study participants' were 150 children with acute gastroenteritis and vomiting who were moderately dehydrated, had not responded to oral rehydration therapy and without any electrolyte abnormalities. 20-30 cc/kg of a crystalloid solution was given intravenously over 2 hours and the control group was admitted in the emergency department (ED) for a standard 24 hour hydration. Effectiveness of rapid intravenous rehydration in the resolution of vomiting in children with acute gastroenteritis was evaluated. RESULTS: In 63 children of the intervention group (out of 75) vomiting was resolved after rapid IV rehydration and they were discharged. Among them, 12 that did not tolerate oral fluids were admitted. In the control group, 62 patients' vomiting was resolved in the first 4 hours after admission, and there was no significant difference between the two groups regarding resolution of vomiting. CONCLUSIONS: Rapid intravenous rehydration in children with moderate dehydration and vomiting due to gastroenteritis is effective in reducing admission rates in the ED. PMID- 27355089 TI - Sudden Suspected Death in Emergency Department: Autopsy Results. AB - OBJECTIVES: Sudden deaths occur within 24 hours after symptoms' onset and are caused by cardiac, neurological and pulmonary diseases. Autopsy is the gold standard in determining cause of death. In this study, death's etiology was evaluated in cases applied to our department that underwent autopsy with sudden death indication. METHODS: This study included cases aged 18 or older with sudden, suspected, non-traumatic death applying to our department between 2008 and 2012. Patients' age, sex, death time, co-morbid diseases, initial signs, cardiac rhythm, and autopsy findings were recorded after reviewing patient charts. RESULTS: The study included 46 patients. Mean age was 45.73+/-19.6. Of the cases, 84.78% applied to emergency with cardiopulmonary arrest. Thirty-two cases (69.6%) were male. The most frequent cause of death was cardiovascular diseases (52.2%), followed by central nervous system disorders (21.7%), intoxications (15.2%), and respiratory diseases (10.9%). The most common diseases were myocardial infarction (45.7%), subarachnoid hemorrhage (8.7%), and chronic obstructive pulmonary disease. There were three drug ingestions, three carbon monoxide intoxications, and one corrosive material ingestion among the intoxication cases. CONCLUSIONS: Sudden deaths are rarely encountered. Emergency clinicians should consider cause in differential diagnosis and provide appropriate approaches at first evaluation. PMID- 27355090 TI - The Analysis of Escherichia Coli Resistance in Urine Culture and in Antibiograms as Requested by Emergency Service. AB - OBJECTIVES: The aim of this study was to determine the antibiotic resistance of infectious and non-infectious E. coli species in order to increase the success of empirical antibiotic treatment in urinary system infections. METHODS: The antibiotic susceptibility of 464 E. coli strains that were isolated from urine samples of patients who visited Derince Training and Research Hospital Emergency Department between January 1 and December 31, 2012 were retrospectively evaluated from records. The antibiogram results were classified as susceptible, moderately susceptible or resistant. Moderately susceptible strains were assumed to be resistant. RESULTS: Bacterial proliferation was seen in 563 (28.1%) of the 1998 urine cultures tested. One hundred and twelve cultures could not be evaluated due to contamination, and there was no proliferation in 1323 cultures. E. coli strains were isolated in 464 (82.4%) of the cultures in which proliferation was seen. Three hundred and sixty seven (79%) of the patients were female, 97 (21%) were male, and the mean age of all of the patients was 41.1+/-24.1 years (min: 1, max: 90). The antibiograms of the E. coli strains revealed that meropenem had the lowest resistance (0%), while ampicillin-sulbactam had the highest resistance (36.8%). CONCLUSIONS: In this study, we investigated the antibiotic resistance of E. coli strains isolated from urine cultures in our region. Future studies, perhaps similar to this one, can be performed in the future to increase the success of treatments. PMID- 27355091 TI - Spontaneous Bladder Rupture and Pelvic Fracture Due To Bladder Cancer. AB - Bladder rupture is a rare complication following bladder cancer, but has a high mortality rate. Since bladder rupture is an emergency, the diagnosis and treatment of the cancer is usually delayed. Here we report a 56-year-old male patient who presented to our emergency department with severe abdominal pain, abdominal distension, left leg pain and difficulty in walking without history of significant trauma and ended up with diagnoses of spontaneous bladder rupture and non-traumatic pelvic fracture caused by bladder carcinoma. PMID- 27355092 TI - A Case of Ramsay Hunt Syndrome with Atypical Presentation. AB - Ramsay Hunt syndrome is a rare complication of herpes zoster which results from the reactivation of the latent varicella-zoster virus in the geniculate ganglion. Although facial nerve is the most common affected nerve in Ramsay Hunt syndrome, other cranial and cervical nerves can also be affected. We present an atypical case of Ramsay Hunt syndrome in a 42-year-old male, with cervical nerve involvement. As spontaneous recovery rate in Ramsay Hunt syndrome is low, early diagnosis and treatment plays a key role in full recovery of paralysis. PMID- 27355094 TI - Cancer incidence vs. FM radio transmitter density. AB - BACKGROUND: In 2002, a strong association was highlighted between local melanoma incidence and the number of locally covering main Frequency Modulation (FM) transmitters in Sweden. This study investigated whether an association also exists between melanoma incidence and the average density of main FM transmitters in different European countries. METHODS: Twenty-three different European countries were asked to disclose the number of main transmitters used for the FM broadcasting band (87.5-108 MHz) in the respective country. Incidences of melanoma, breast cancer and all cancers together per country were correlated with their respective average density of transmitters per 10,000 km(2). FINDINGS: Both melanoma and breast cancer, as well as all cancers together, appear to be significantly associated with the density of main FM broadcasting transmitters in the European countries examined. INTERPRETATION: The findings present strong support to the earlier presented hypothesis that body-resonant broadcasting radiation emitted by horizontally polarized main FM transmitters has an immune disturbing effect. FUNDING: This study was financed by internal funds within Hallberg Independent Research only. PMID- 27355095 TI - Priming Sexual and Romantic Representations in Two Media Environments: Sex Encourages and Romance Discourages Sexual Permissiveness ... Sometimes. AB - Two experiments (Ns = 314, 447) were used to evaluate the effectiveness of sexual cues in temporarily increasing young adults' self-reported sexual permissiveness, as well as the effects of romantic cues in temporarily decreasing permissiveness. Participants were exposed to sexual or romantic cues embedded as a theme-defining component of an online game (Study 1) or in advertisements peripheral to the online game (Study 2). Sexual and romantic conditions were compared against a control condition. As hypothesized, participants in the romantic conditions rated themselves lower in sexual permissiveness, compared to participants in the sexual and control conditions, particularly when participants positively evaluated the online game experience. Findings suggest that exposure to entertaining media depictions of two people, as a committed couple, expressing love, as well as lust, for each other might deter young adults from considering engagement in casual sexual encounters indicative of "hookup culture." PMID- 27355096 TI - Catalytic Asymmetric [4 + 1] Annulation of Sulfur Ylides with Copper-Allenylidene Intermediates. AB - The first copper-catalyzed asymmetric decarboxylative [4 + 1] cycloaddition of propargylic carbamates and sulfur ylides was successfully developed. This strategy led to a series of chiral indolines with synthetically flexible alkyne groups in good yields and with high enantio- and diastereoselectivities (up to 99% yield, 98% ee, and >95:5 dr). A possible mechanism and stereoinduction mode with copper-allenylidenes were proposed as the possible dipolar intermediate. PMID- 27355097 TI - Aqueous Peptide-TiO2 Interfaces: Isoenergetic Binding via Either Entropically or Enthalpically Driven Mechanisms. AB - A major barrier to the systematic improvement of biomimetic peptide-mediated strategies for the controlled growth of inorganic nanomaterials in environmentally benign conditions lies in the lack of clear conceptual connections between the sequence of the peptide and its surface binding affinity, with binding being facilitated by noncovalent interactions. Peptide conformation, both in the adsorbed and in the nonadsorbed state, is the key relationship that connects peptide-materials binding with peptide sequence. Here, we combine experimental peptide-titania binding characterization with state-of-the-art conformational sampling via molecular simulations to elucidate these structure/binding relationships for two very different titania-binding peptide sequences. The two sequences (Ti-1, QPYLFATDSLIK; Ti-2, GHTHYHAVRTQT) differ in their overall hydropathy, yet via quartz-crystal microbalance measurements and predictions from molecular simulations, we show these sequences both support very similar, strong titania-binding affinities. Our molecular simulations reveal that the two sequences exhibit profoundly different modes of surface binding, with Ti 1 acting as an entropically driven binder while Ti-2 behaves as an enthalpically driven binder. The integrated approach presented here provides a rational basis for peptide sequence engineering to achieve the in situ growth and organization of titania nanostructures in aqueous media and for the design of sequences suitable for a range of technological applications that involve the interface between titania and biomolecules. PMID- 27355098 TI - Mesostructured HfxAlyO2 Thin Films as Reliable and Robust Gate Dielectrics with Tunable Dielectric Constants for High-Performance Graphene-Based Transistors. AB - We introduce a reliable and robust gate dielectric material with tunable dielectric constants based on a mesostructured HfxAlyO2 film. The ultrathin mesostructured HfxAlyO2 film is deposited on graphene via a physisorbed-precursor assisted atomic layer deposition process and consists of an intermediate state with small crystallized parts in an amorphous matrix. Crystal phase engineering using Al dopant is employed to achieve HfO2 phase transitions, which produce the crystallized part of the mesostructured HfxAlyO2 film. The effects of various Al doping concentrations are examined, and an enhanced dielectric constant of ~25 is obtained. Further, the leakage current is suppressed (~10(-8) A/cm(2)) and the dielectric breakdown properties are enhanced (breakdown field: ~7 MV/cm) by the partially remaining amorphous matrix. We believe that this contribution is theoretically and practically relevant because excellent gate dielectric performance is obtained. In addition, an array of top-gated metal-insulator graphene field-effect transistors is fabricated on a 6 in. wafer, yielding a capacitance equivalent oxide thickness of less than 1 nm (0.78 nm). This low capacitance equivalent oxide thickness has important implications for the incorporation of graphene into high-performance silicon-based nanoelectronics. PMID- 27355099 TI - Bis(carboxyphenyl)-1,2,4-triazole Based Metal-Organic Frameworks: Impact of Metal Ion Substitution on Adsorption Performance. PMID- 27355100 TI - Factors Affecting Recruitment of Participants for Studies of Diabetes Technology in Newly Diagnosed Youth with Type 1 Diabetes: A Qualitative Focus Group Study with Parents and Children. AB - BACKGROUND: Relatively little is known about parents' or children's attitudes toward recruitment for, and participation in, studies of new diabetes technologies immediately after diagnosis. This study investigated factors affecting recruitment of participants for studies in newly diagnosed youth with type 1 diabetes. METHODS: Qualitative focus group study incorporating four recorded focus groups, conducted in four outpatient pediatric diabetes clinics in large regional hospitals in England. Participants comprised four groups of parents (n = 22) and youth (n = 17) with type 1 diabetes, purposively sampled on the basis of past involvement (either participation or nonparticipation) in an ongoing two-arm randomized trial comparing multiple daily injection with conventional continuous subcutaneous insulin infusion regimens from the onset of type 1 diabetes. RESULTS: Stress associated with diagnosis presents significant challenges in terms of study recruitment, with parents demonstrating varied levels of willingness to be approached soon after diagnosis. Additional challenges arise regarding the following: randomization when study arms are perceived as sharply differentiated in terms of therapy effectiveness; burdens arising from study participation; and the need to surrender new technologies following the end of the study. However, these challenges were mostly insufficient to rule out study participation. Participants emphasized the benefits and reassurance arising from support provided by staff and fellow study participants. CONCLUSIONS: Recruitment to studies of new diabetes technologies immediately after diagnosis in youth presents significant challenges, but these are not insurmountable. The stress and uncertainty arising from potential participation may be alleviated by personalized discussion with staff and peer support from fellow study participants. PMID- 27355102 TI - Chinese Herb Use by Patients at a San Francisco Chinatown Public Health Center. AB - OBJECTIVES: Chinese herbal medicine (CHM) use has not been well characterized in persons living in the United States who receive care by Western-trained healthcare providers. The primary objective of this study was to characterize use of CHM taken in the last 12 months by patients seen at a Chinatown public health center. DESIGN: Convenience sample survey. SETTING: Data collection occurred over 3 months at a San Francisco Chinatown public health center. PARTICIPANTS: Adult patients visiting their primary care provider. INTERVENTIONS: Completion of a voluntary 24-question survey on CHM use. OUTCOME MEASURES: Prevalence, type, and indications for use. RESULTS: Survey response rate was 29% (50/170). Seventy percent (35/50) of respondents had used CHM in the last 12 months and 94% (33/35) were also taking prescription medicines. The three most commonly used CHM were goji berry (37%), Dioscorea (31%), and ginseng (23%). The most common indications for herbs used in the last 12 months were general wellness (34%), cold/flu (25%), and headache (6%). Sixty-four percent of respondents had used Western medicine in combination with CHM within the last 12 months. Sixty-nine percent of respondents who used CHM did not tell their Western provider about this use. No patient had CHM use documented in the electronic medical record. CONCLUSIONS: Patients seen at a Chinatown public health center frequently used CHM products in conjunction with Western prescription medicines. Providers should routinely enquire about CHM use for health as a soup, tea, food, or pill and document this use in the medical record. PMID- 27355101 TI - Assembly and Mechanical Properties of the Cargo-Free and Cargo-Loaded Bacterial Nanocompartment Encapsulin. AB - Prokaryotes mostly lack membranous compartments that are typical of eukaryotic cells, but instead, they have various protein-based organelles. These include bacterial microcompartments like the carboxysome and the virus-like nanocompartment encapsulin. Encapsulins have an adaptable mechanism for enzyme packaging, which makes it an attractive platform to carry a foreign protein cargo. Here we investigate the assembly pathways and mechanical properties of the cargo-free and cargo-loaded nanocompartments, using a combination of native mass spectrometry, atomic force microscopy and multiscale computational molecular modeling. We show that encapsulin dimers assemble into rigid single-enzyme bacterial containers. Moreover, we demonstrate that cargo encapsulation has a mechanical impact on the shell. The structural similarity of encapsulins to virus capsids is reflected in their mechanical properties. With these robust mechanical properties encapsulins provide a suitable platform for the development of nanotechnological applications. PMID- 27355104 TI - AgSCF3-Mediated Oxidative Trifluoromethythiolation of Alkynes with Dearomatization to Synthesize SCF3-Substituted Spiro[4,5]trienones. AB - A new method for the AgSCF3-mediated radical cascade difunctionalizing trifluoromethythiolation of alkynes with dearomatization is developed. This protocol provides a novel route to SCF3-substituted spirocyclic compounds via the formation of one C-SCF3 bond, one C-C bond, and one C-O double bond in a single step. PMID- 27355103 TI - Clinically significant psychiatric symptoms among male carriers of the fragile X premutation, with and without FXTAS, and the mediating influence of executive functioning. AB - OBJECTIVES: To clarify the neuropsychiatric phenotype of fragile X-associated tremor/ataxia syndrome (FXTAS), and assess the extent to which it is mediated by the dysexecutive syndrome that is a major feature of the disorder. METHODS: We examined the prevalence of clinically meaningful psychiatric symptoms among male carriers of the fragile X premutation, with and without FXTAS, in comparison with men with a normal allele. Measures included the Neuropsychiatric Inventory (NPI), Symptom Checklist-90-R (SCL-90-R), and the Behavioral Dyscontrol Scale, a measure of executive functioning. Between-group differences were evaluated using logistic regression, followed by a mediation analysis with ordinary least squares regression to assess the contribution of dysexecutive syndrome to the observed psychiatric domains. RESULTS: Men with FXTAS showed higher rates of clinically significant symptoms overall and in specific domains: somatization, obsessive compulsive, depression, anxiety, psychoticism, agitation/aggression, apathy/indifference, irritability, and nighttime behavior problems. Post hoc analyses suggested that findings of psychoticism among men with FXTAS may be associated with participants' accurate acknowledgment of cognitive and physical dysfunction, rather than reflecting psychosis. Asymptomatic carriers showed no evidence of clinically significant psychiatric symptoms, but when all carriers were compared with men having a normal FMR1 allele, executive function deficits were found to mediate scores in several domains on both NPI and SCL-90-R. CONCLUSIONS: Building on prior research, the results provide evidence that the psychiatric phenotype for men includes clinically meaningful depression, hostility, and irritability, in association with behavioral and attentional disinhibition. It is likely that these problems reflect the effects of impaired executive functioning. PMID- 27355105 TI - Outcomes of Patients in Long-Term Opioid Maintenance Treatment. AB - BACKGROUND: Despite the importance of duration of opioid maintenance treatment (OMT), only few studies have reported outcomes of long-term OMT. OBJECTIVES: To describe outcomes of long-term (> 5 years) OMT patients with respect to substance use, physical and mental health, and socioeconomic characteristics. METHODS: Patients (n = 160) were recruited from 15 OMT offices in different regions of Germany. Data were collected using a structured interview at baseline, and clinical recordings, including urine drug screenings, during 12 monhts follow-up. RESULTS: Patients had a mean age of 44 years. During follow-up, 23% of patients showed indications of an alcohol problem. Cannabis was used by 56%, often frequently. Heroin was used by 28%, mostly infrequently. Three quarters of patients either had a non-substance related mental disorder (48.1%, most frequently affective and anxiety disorders) or somatic diagnosis (61.3%, frequently hepatitis C, HIV, or cardiovascular diseases), or both. Unemployment rate was 43.1% at baseline (27% for patients without comorbidity) and remained generally stable during follow-up. No arrests or incarcerations were recorded. During follow-up, 2.5% of patients prematurely terminated OMT, 2.5% regularly completed OMT. CONCLUSIONS: The sample as a whole was characterized by stable living conditions, high unemployment, low illicit opiate use, and a high retention rate. Continuation of OMT could enable further treatment of comorbidity and prevent resumption of a drug-dominated lifestyle. But it may well be asked how within the context of OMT further improvements can be achieved, especially with regard to further decrease of alcohol use and the treatment of depression. PMID- 27355106 TI - Cyberbullying Victimization in Adolescents as Related to Body Esteem, Social Support, and Social Self-Efficacy. AB - The authors examined cyberbullying victimization in the context of issues of key importance to youth: body esteem, social support, and social self-efficacy. Research has found that traditional peer-bullying victimization is significantly correlated with low body esteem in Western societies, especially pertaining to weight (R. Puhl & J. Luedicke, 2012 ). Studies have also found a relationship among bullying victimization, appearance-related bullying, low body esteem, and psychosocial difficulties among youth (L. E. Park, R. M. Calogero, A.F. Young, & A. Diraddo, 2010 ). However, the emergence of cyberbullying, characterized by its own special features (P. K. Smith et al., 2008 ), has raised a salient need to explore the relationship between cyber victimization and body esteem, no less important with social framework, because both are key components in adolescents' lives that may be associated with cyberbullying victimization. The authors examined these relationships among 204 Israeli adolescents 14-16 years old. The results indicate a noteworthy prevalence (45%) of cyber victims. Cyber victimization is significantly correlated with low body esteem and low social support and social self-efficacy. Low body esteem and low social support predicted the probability of being a cyber victim. The results extend the knowledge about potential personal and social risk factors for cyber victimization during adolescence. Implications for specific intervention programs are discussed. PMID- 27355107 TI - Sex differences and hormonal effects on gut microbiota composition in mice. AB - We previously reported quantitation of gut microbiota in a panel of 89 different inbred strains of mice, and we now examine the question of sex differences in microbiota composition. When the total population of 689 mice was examined together, several taxa exhibited significant differences in abundance between sexes but a larger number of differences were observed at the single strain level, suggesting that sex differences can be obscured by host genetics and environmental factors. We also examined a subset of mice on chow and high fat diets and observed sex-by-diet interactions. We further investigated the sex differences using gonadectomized and hormone treated mice from 3 different inbred strains. Principal coordinate analysis with unweighted UniFrac distances revealed very clear effects of gonadectomy and hormone replacement on microbiota composition in all 3 strains. Moreover, bile acid analyses showed gender-specific differences as well as effects of gonodectomy, providing one possible mechanism mediating sex differences in microbiota composition. PMID- 27355127 TI - A new three-dimensional conformal radiotherapy (3DCRT) technique for large breast and/or high body mass index patients: evaluation of a novel fields assessment aimed to reduce extra-target-tissue irradiation. AB - OBJECTIVE: To develop an alternative three-dimensional treatment plan with standardized fields class solution for whole-breast radiotherapy in patients with large/pendulous breast and/or high body mass index (BMI). METHODS: Two treatment plans [tangential fields and standardized five-fields technique (S5F)] for a total dose of 50 Gy/25 fractions were generated for patients with large breasts [planning target volume (PTV) >1000 cm(3) and/or BMI >25 kg m(-2)], supine positioned. S5F plans consist of two wedged tangential beams, anteroposterior: 20 degrees for the right breast and 340 degrees for the left breast, and posteroanterior: 181 degrees for the right breast and 179 degrees for the left breast. A field in field in medial-lateral beam and additional fields were added to reduce hot spot areas and extra-target-tissue irradiation and to improve dose distribution. The percentage of PTV receiving 95% of the prescribed dose (PTV V95%), percentage of PTV receiving 105% of the prescribed dose (PTV V105%), maximal dose to PTV (PTV Dmax), homogeneity index (HI) and conformity index were recorded. V10%, V20%, V105% and V107% of a "proper" normal tissue structure (body PTV healthy tissue) were recorded. Statistical analyses were performed using SYSTAT v.12.0 (SPSS, Chicago, IL). RESULTS: In 38 patients included, S5F improved HI (8.4 vs 10.1; p <= 0.001) and significantly reduced PTV Dmax and PTV V105%. The extra-target-tissue irradiation was significantly reduced using S5F for V105% (cm(3)) and V107% (cm(3)) with a very high difference in tissue irradiation (46.6 vs 3.0 cm(3), p <= 0.001 for V105% and 12.2 vs 0.0 cm(3), p <= 0.001 for V107% for tangential field and S5F plans, respectively). Only a slight increase in low dose extra-target-tissue irradiation (V10%) was observed (2.2719 vs 1.8261 cm(3), p = 0.002). CONCLUSION: The S5F technique in patients with large breast or high BMI increases HI and decreases hot spots in extra-target-tissues and can therefore be easily implemented in breast cancer radiotherapy. ADVANCES IN KNOWLEDGE: The treatment planning strategy proposed in this study has several advantages: (a) it is extremely reliable as the standard supine positioning is used; (b) the standardized class solution allows for widespread use; PMID- 27355128 TI - Methodologic Considerations for Collecting Patient-reported Outcomes from Unselected Surgical Patients. AB - BACKGROUND: The impact of surgery on health is only appreciated long after hospital discharge. Furthermore, patients' perceptions of postoperative health are not routinely ascertained. The authors instituted the Systematic Assessment and Targeted Improvement of Services Following Yearlong Surgical Outcomes Surveys (SATISFY-SOS) registry to evaluate patients' postoperative health based on patient-reported outcomes (PROs). METHODS: This article describes the methods of establishing the SATISFY-SOS registry from an unselected surgical population, combining perioperative PROs with information from electronic medical records. Patients enrolled during their preoperative visit were surveyed at enrollment, 30 days, and 1-yr postoperatively. Information on PROs, including quality of life, return to work, pain, functional status, medical complications, and cognition, was obtained from online, mail, or telephone surveys. RESULTS: Using structured query language, 44,081 patients were identified in the electronic medical records as having visited the Center for Preoperative Assessment and Planning for preoperative assessment between July 16, 2012, and June 15, 2014, and 20,719 patients (47%) consented to participate in SATISFY-SOS. Baseline characteristics and health status were similar between enrolled and not enrolled patients. The response rate for the 30-day survey was 62% (8% e-mail, 73% mail, and 19% telephone) and for the 1-yr survey was 71% (13% e-mail, 78% mail, and 8% telephone). CONCLUSIONS: SATISFY-SOS demonstrates the feasibility of establishing a PRO registry reflective of a busy preoperative assessment center population, without disrupting clinical workflow. Our experience suggests that patient engagement, including informed consent and multiple survey modalities, enhances PROs collection from a large cohort of unselected surgical patients. Initiatives like SATISFY-SOS could promote quality improvement, enable efficient perioperative research, and facilitate outcomes that matter to surgical patients. PMID- 27355129 TI - Nanoscopic Thermodynamics. AB - Conventional thermodynamics for bulk substances encounters challenges when one considers materials on the nanometer scale. Quantities such as entropy, enthalpy, free energy, melting temperature, ordering temperature, Debye temperature, and specific heat no longer remain constant but change with the crystal dimension, size, and morphology. Often, one phenomenon is associated with a variety of theories from different perspectives. Still, a model that can reconcile the size and shape dependence of the thermal properties of the nanoscaled substances remains one of the goals of nanoscience and nanotechnology. This Account highlights the nanoscopic thermodynamics for nanoparticles, nanowires, and nanofilms, with particular emphasis on the bond energy model. The central idea is that the atomic cohesive energy determines the thermodynamic performance of a substance and the cohesive energy varies with the atomic coordination environment. It is the cohesive energy difference between the core and the shell that dictates the nanoscopic thermodynamics. This bond energy model rationalizes the following: (i) how the surface dangling bonds depress the melting temperature, entropy, and enthalpy; (ii) how the order-disorder transition of the nanoparticles depends on particle size and how their stability may vary when they are embedded in an appropriate matrix; (iii) predictions of the existence of face centered cubic structures of Ti, Zr, and Hf at small size; (iv) how two elements that are immiscible in the bulk can form an alloy on the nanoscale, where the critical size can be predicted. The model has enabled us to reproduce the size and shape dependence of a number of physical properties, such as melting temperature, melting entropy, melting enthalpy, ordering temperature, Gibbs free energy, and formation heat, among others, for materials such as Pd, Au, Ag, Cu, Ni, Sn, Pb, In, Bi, Al, Ti, Zr, Hf, In-Al, Ag-Ni, Co-Pt, Cu-Ag, Cu-Ni, Au-Ni, Ag Pt, and Au-Pt on the nanometer scale. Furthermore, this model predicts the phenomena of the thermal stability of metal particles on graphene, the superheating of embedded nanoparticles, the order-disorder transition of nanoalloys, the size-temperature phase diagram for low-dimensional solids and the alloying ability on the nanoscale. Extensions of this model may lead to the design of new functional nanomaterials. PMID- 27355130 TI - The ABLA-BOX: An In Vitro Module of Hybrid Atrial Fibrillation Ablation. AB - OBJECTIVE: We present the first testing study on the ABLA-BOX, a new in vitro module of hybrid atrial fibrillation ablation. METHODS: ABLA-BOX consists of two chambers that mimic the epicardial and endocardial sides of the heart. The septum between chambers provides catheter access on both sites of the cardiac tissue. A circuit, filled with freshly obtained porcine blood, including a pump, an oxygenator, and a heating device, circulate the blood inside the system. Left atrial fresh tissue is mounted on a tissue holder and magnetically fixed. Epicardial and endocardial catheters are fixed on the catheter holders and blocked with the locker knob. The system allows control of ablation force, flow rate, temperature, and flow pattern. RESULTS: Epicardial contact force of 100 g and endocardial force of 30 g resulted in larger lesion volumes (P < 0.001), areas (P < 0.001), and lesion diameters (P = 0.03 and P = 0.008), than the combination of 100/20 g. In addition, with a flow rate of 5 L/min, lesion volumes (P = 0.02), areas (P < 0.001), and diameters (both, P < 0.001) were significantly larger in comparison with those of 3 L/min. Furthermore, dimensions (both, P < 0.001), volume (P < 0.001), and area (P < 0.001) of the lesions at a circulating blood temperature of 38.0 degrees C were larger than with a lower blood temperature (36.0 degrees C). Finally, ablations made under stable flow pattern resulted in greater lesion diameters (P = 0.04 and P = 0.03) as well as larger volumes (P = 0.02) and areas (P = 0.03) than under turbulent-like flow reproduced with the system rotor set to 400 rpm. CONCLUSIONS: The ABLA-BOX allowed easy hybrid ablation with different setups, which can provide cardiologists and cardiac surgeons with reliable and more valuable insights. PMID- 27355131 TI - Danshen injection ameliorates STZ-induced diabetic nephropathy in association with suppression of oxidative stress, pro-inflammatory factors and fibrosis. AB - Diabetic nephropathy (DN) is one of the most frequent complications in diabetes mellitus. This study aimed to explore whether Danshen injection is protective to renal tissue in diabetes. Intraperitoneal injection of streptozotocin (STZ) (60mg/kg) was used to induce diabetes in rats. Some STZ-induced diabetic rats were also intraperitoneally injected with Danshen solution at two different dosages (0.5 or 1ml/kg/day) for 6weeks. Our results showed that serum creatinine (sCr) and blood urea nitrogen were significantly increased in STZ-induced diabetic rats, which was alleviated upon Danshen injection. Danshen injection was also found to ameliorate hypertrophy and dilatation of renal tubule and glomeruli possibly by decreasing the expression of collagen and fibronectin in association with suppression of TGF-beta1/Smad pathway. Further investigation revealed that Danshen injection could increase the activity of superoxide dismutase (SOD), and reduce reactive oxygen species (ROS) and malondialdehyde (MDA) levels in STZ induced diabetic rats, indicating suppression of oxidative stress. In addition, we also found that Danshen injection could suppress IkappaB/NF-kappaB signaling pathway and reduce the level of a number of pro-inflammatory factors, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in the diabetic renal tissue, indicating suppression of inflammation. In conclusion, our results demonstrated that Danshen injection may rescue STZ-induced diabetic nephropathy, possibly via suppressing the oxidative stress, inflammatory responses and fibrosis progression. PMID- 27355132 TI - Remote ischemic postconditioning protects against renal ischemia/reperfusion injury by activation of T-LAK-cell-originated protein kinase (TOPK)/PTEN/Akt signaling pathway mediated anti-oxidation and anti-inflammation. AB - BACKGROUND: Recent clinical and animal studies suggested that remote limb ischemic postconditioning (RIPostC) can invoke potent cardioprotection or neuroprotection. However, the effect and mechanism of RIPostC against renal ischemia/reperfusion injury (IRI) are poorly understood. T-LAK-cell-originated protein kinase (TOPK) is crucial for the proliferation and migration of tumor cells. However, the function of TOPK and the molecular mechanism underlying renal protection remain unknown. Therefore, this study aimed to evaluate the role of TOPK in renoprotection induced by RIPostC. MATERIALS AND METHODS: The renal IRI model was induced by left renal pedicle clamping for 45min followed by 24h reperfusion and right nephrectomy. All mice were intraperitoneally injected with vehicle, TOPK inhibitor HI-TOPK-032 or Akt inhibitor LY294002. After 24h reperfusion, renal histology, function, and inflammatory cytokines and oxidative stress were assessed. The proteins were measured by Western blotting. RESULTS: The results showed that RIPostC significantly protected the kidneys against IRI. The protective effects were accompanied by the attenuation of renal dysfunction, tubular damage, inflammation and oxidative stress. In addition, RIPostC increased the phosphorylation of TOPK, PTEN, Akt, GSK3beta and the nuclear translocation of Nrf2 and decreased the nuclear translocation of NF-kappaB. However, all of the above renoprotective effects of RIPostC were eliminated either by the inhibition of TOPK or Akt with HI-TOPK-032 or LY294002. CONCLUSIONS: The current data reveal that RIPostC protects against renal IRI via activation of TOPK/PTEN/Akt signaling pathway mediated anti-oxidation and anti-inflammation. PMID- 27355134 TI - How do cells sense actin cortex-free membrane? PMID- 27355133 TI - Ortho-eugenol exhibits anti-nociceptive and anti-inflammatory activities. AB - Ortho-eugenol is a much used phenylpropanoid whose ability to reduce pain and inflammation has never been studied. Researching ortho-eugenol's antinociceptive and anti-inflammatory activity, and its possible mechanisms of action is therefore of interest. The administration of vehicle, ortho-eugenol (50, 75 and 100mg/kg i.p.), morphine (6mg/kg, i.p.) or dexamethasone (2mg/kg, s.c.) occurred 30min before the completion of pharmacological tests. Pretreatment with ortho eugenol did not change motor coordination test results, but reduced the number of writhes and licking times in the writhing test and glutamate test, respectively. The reaction time from thermal stimulus was significantly increased in the hot plate test after administration of ortho-eugenol. Treatment with yohimbine reversed the antinociceptive effect of ortho-eugenol, suggesting involvement of the adrenergic system. In anti-inflammatory tests, ortho-eugenol inhibited acetic acid induced vascular permeability and leukocyte migration, reducing TNF-alpha and IL-1beta by virtue of its suppression of NF-kappaB and p38 phosphorylated forms in the peritonitis test. From these results, ortho-eugenol antinociceptive effects mediated by the adrenergic system and anti-inflammatory activity through regulation of proinflammatory cytokines and phosphorylation of NF-kB and p38 become evident for the first time. PMID- 27355135 TI - Measuring the Real Clinical Impact of Randomized Clinical Trials in Oncology: Beyond Citation Counts. PMID- 27355136 TI - Design of folding-based impedimetric aptasensor for determination of the nonsteroidal anti-inflammatory drug. AB - In this work, a novel sensing nanocomposite with highly dispersed platinum nanoparticles (PtNPs) on carbon nanotubes (CNTs) functionalized with polyethyleneimine (PEI) has been developed as a platform for immobilization of diclofenac (DIF) aptamer. PtNPs/PEI/CNTs nanocomposite provided abundant NH2 groups for the immobilization of DIF-specific aptamer. Attachment of DIF-aptamer at the surface of modified electrode was performed through the formation of phosphoramidate bonds between the amino group of PEI and the phosphate group of the aptamer at the 5' end. Nickel hexacyanoferrate (NiHCF) as signal probe was electrodeposited at the surface of nanocomposite by a simple electrodeposition method including two consecutive procedures. Under optimal conditions, DIF was detected by impedance spectroscopy (EIS) quantitatively. By adding DIF as the target at the surface of modified electrode, the aptamer specifically binds to DIF and its end folds into a DIF-binding junction, which leads to retarding the interfacial electron transfer of the probe at the surface of modified electrode. Sensitive quantitative detection of DIF was carried out by monitoring the increase of charge transfer resistance (Rct) by increasing the DIF concentration. The proposed aptasensor showed a good detection range from 10 to 200 nM with an unprecedented detection limit of 2.7 nM. PMID- 27355137 TI - Determinants of virological response to antiretroviral therapy: socio-economic status still plays a role in the era of cART. Results from the ANRS-VESPA 2 study, France. AB - BACKGROUND: Disparities in combined antiretroviral therapy (cART) outcomes have been consistently reported among people living with HIV (PLWHIV). The present study aims at investigating the mechanisms underlying those disparities among PLWHIV in France. METHODS: We used data from the Vespa2 survey, a large national cross-sectional survey, representative of HIV-infected people followed at hospitals in 2011. Among participants diagnosed >=1996, HIV treatment-naive at the time of cART initiation and on cART for at least 12 months, the frequency of sustained virological suppression (SVS; undetectable viral load [<50 copies/ml] for at least 6 months) at the time of the survey, was assessed and its social determinants were measured through logistic regression, accounting for clinical and biological determinants of response to cART. RESULTS: Among 1,246 participants, 77.7% had achieved SVS. SVS was less frequent among those unemployed (0.6 [range 0.3-1.0]) and those with the lowest level of education (0.4 [range 0.2-0.9]). The late presenters, diagnosed at a CD4+ T-cell count <200/mm3 (0.5 [range 0.3-0.9]) and the late starters, diagnosed at a CD4+ T-cell count >200 but initiating cART at CD4+ T-cell count <200 (0.3 [range 0.1-0.8]) were less likely than the ideal starters (>=350 CD4+ T-cells/mm3 at cART initiation) to achieve SVS, as were those who reported suboptimal adherence versus those reporting optimal adherence (0.4 [range 0.2-0.7]). In bivariate analyses, material deprivation, discrimination and a weak social network were also associated with a poorer treatment response. CONCLUSIONS: Structural social factors remain strong determinants of treatment response and should be addressed in a broad approach of care, but wider political issues should also be investigated. PMID- 27355138 TI - Systemic delivery of siRNA by T7 peptide modified core-shell nanoparticles for targeted therapy of breast cancer. AB - Systemic delivery of siRNA is the most challenging step to transfer RNAi to clinical application for breast cancer therapy. In this study, the tumor targeted, T7 peptide modified core-shell nanoparticles (named as T7-LPC/siRNA NPs) were constructed to achieve effective systemic delivery of siRNA. The core shell structure of T7-LPC/siRNA NPs enables them to encapsulate siRNA in the core and protect it from RNase degradation during circulation. In vitro cellular uptake and gene silencing experiments demonstrated that T7-LPC/siEGFR NPs could deliver EGFR siRNA into breast cancer cells through receptor mediated endocytosis and effectively down-regulate the EGFR expression. In vivo distribution study proved the T7-LPC/siRNA NPs could deliver fluorescence labeled siRNA to the tumor site more efficiently than the non-targeted PEG-LPC/siRNA NPs after intravenous administration. Furthermore, the experiments of in vivo tumor therapy confirmed that intravenous administration of T7-LPC/siEGFR NPs led to an effective EGFR down-regulation and an obvious inhibition of breast tumor growth, with little activation of immune responses and negligible body weight loss. These results suggested that T7-LPC/siRNA NPs could be an effective and safe systemic siRNA delivery system for RNAi-based breast cancer therapy. PMID- 27355139 TI - Surgical Treatment of Intracardiac-Extending Intravenous Leiomyomatosis: A Single Center Experience. AB - BACKGROUND: Few data were known on surgical management of intracardiac-extending in patients with intravenous leiomyomatosis (IVL). METHODS: From June 2007 to December 2014, six women (mean age, 39.3 +/- 7.5 years; range, 24-55 years) with intracardiac-extending IVL were treated surgically at our hospital. Data were obtained from medical and pathological records, including characteristics of patients, surgical management, and follow-up. RESULTS: Surgery was performed successfully in all patients. Of 6 patients, 4 underwent one-stage operation and 2 underwent two-stage procedures. Circulatory arrest with hypothermia was used for a cardiotomy combined with venotomy in 5 patients. Complete resection was done in 5 patients. There were no perioperative deaths or complications in any of the patients. Hospital stay was 11.2 +/- 2.9 days (range 7-15 days). All patients were followed-up for a mean of 41.0 +/- 19.1 months (range, 17-69 months) after surgery. A recurrence of pelvic mass was found in 1 patient, but no symptoms or intravenous mass were reported. No obstruction occurred in any patient with a venotomy. CONCLUSION: Surgery is a better therapy for IVL and complete removal has favorable outcomes. PMID- 27355140 TI - Recurrent Left Atrial Botyroid Rhabdomyosarcoma. AB - Primary heart tumors are extremely rare and their frequency ranges from approximately 0.01-0.3% in autopsy series. Nearly one quarter of all primary cardiac tumors are malignant tumors such as sarcoma. Rhabdomyosarcoma is the second most common malignant primary tumor of the heart following angiosarcoma.Primary cardiac tumors present with one or more of the symptoms of the classic triad: cardiac symptoms and signs resulting from intracardiac obstruction; signs of systemic embolization; and systemic or constitutional symptoms. The prognosis after surgery is usually excellent in case of benign tumors, but is unfortunately still limited in localized malignant diseases [Butany 2005].In this case report we present a 45-year-old female patient operated three times in 9 years because of left atrial tumor. PMID- 27355141 TI - The Influence of Metabolic Syndrome on Acute Kidney Injury Occurrence after Coronary Artery Bypass Grafting. AB - BACKGROUND: Metabolic syndrome (MetS) is defined as a cluster of systemic abnormalities: hyperglycemia, dyslipidemia, abdominal obesity, and hypertension. Acute kidney injury (AKI) is one of the devastating complications after cardiac surgery. Age, DM, preexisting renal dysfunction, hypertension, impaired left ventricular function, and severe arteriosclerosis of the aorta are the major risk factors for the development of AKI. The purpose of the current study was to analyze the influence of MetS on AKI occurring after coronary artery bypass grafting (CABG). METHODS: We retrospectively reviewed the prospectively collected data of 500 adult patients who underwent isolated CABG surgery with normal renal function (baseline serum creatinine value <1.4 mg/dL) from January 2011 to January 2015. The patients were divided into two groups either having the diagnosis of MetS (Group I) or not (Group II). MetS was diagnosed based on International Diabetes Federation definition. Kidney injury was interpreted according to RIFLE classification. The effect of MetS on AKI after CABG was determined using logistic regression analysis and the results were expressed as odds ratio (OR) with a 95% confidence interval (CI). A P value <.05 was considered statistically significant. RESULTS: Metabolic syndrome was diagnosed in 16.4% of all patients. Postoperative AKI occurred in 26 patients (31.7%) in Group I whereas there were 53 patients (12.7%) in Group II. On logistic regression analysis, the presence of MetS was shown to be associated with increased incidence of postoperative AKI (OR, 3.197; 95% CI, 1.850-5.526; P = .000). CONCLUSION: The presence of MetS seems to be associated with increased incidence of AKI after cardiac surgery. MetS is a modifiable issue; if its components are well controlled its dreadful effects after cardiac surgery might be controlled as well. PMID- 27355142 TI - Multicenter Analysis of Clinical Follow-Ups in Patients with a Star GK Cardiac Valve Replacement for More than One Year. AB - BACKGROUND: Star GK valves were widely used in China, and we studied the clinical follow-up results of patients with Star GK valve implants for more than one year. METHODS: Clinical data were collected from those patients who had Star GK valve implants for over one year. Patients were divided into three groups: (1) AVR group: received aortic valve replacement surgery. Based on the valve model this group was further sub-divided into two groups: 21A group, and 23A group; (2) MVR group: received mitral valve replacement surgery. Based on the valve model this group was further sub-divided into three groups: 25M group, 27M group, and 29M group; (3) DVR group: received combined replacement surgeries including AVR + MVR. According to postoperative follow-up time these patients were divided into two groups: 1-year group and 3-year group. Follow-up data were collected by telephone, outpatient visits, or correspondence. Clinical data were aggregated by professional data scientists to conduct independent analyses. RESULTS: 959 patients were included in the study following Star GK valve implant. Follow-up after 1 year found that thrombosis occurred in 4 cases, hemorrhage in 15 cases, left heart failure in 13 cases, paravalvular leakage in 5 cases, and death due to cardiac causes in 2 cases. CONCLUSION: The long-term efficacy of Star GK valve implants was satisfactory with low incidence of valve-related complications, and following Star GK valve implant, valve and blood were highly compatible and blood component damage was minor. Very low incidence rate of thrombosis was observed following Star GK valve implant, however, attention should be paid to adjust the anticoagulation intensity. PMID- 27355143 TI - Stent Embolism after Coronary Angiography: Case Report. AB - Endovascular interventions are widely performed of late; complications including stent embolism of arteries and veins, dislocation, or malposition of medical devices are frequently seen. Peripheral stent embolisms are generally asymptomatic, but when they cause acute ischemia or severe symptoms like claudication they must be removed. Stents can be removed not only with surgical techniques but also with endovascular maneuvers. In this case report, we state that in symptomatic peripheral arterial embolization cases, surgical intervention is the first choice for treatment due to the complexity and high risk of complications when using endovascular maneuvers. PMID- 27355144 TI - Failing to Prepare is Preparing to Fail: The Known, The Known Unknown, and The Unknown Unknown. AB - Cardiothoracic surgery residents often enter their training with fairly limited prior exposure to the field. Obviously, they need to master the essential knowledge and skills of the discipline during their training. In addition to following a didactic curriculum of one sort or another, much of the necessary knowledge and understanding will accrue from their experiences caring for and operating on the patients who will be under their auspices, not only during their formal training but also after they finish their training. Some of these cases and situations, such as elective cases, allow for careful preparation, while some more urgent or emergent cases require generic, advance preparation in order to be ready to perform optimally in these cases when they arise. And then there will always be cases for which one will not be able to prepare in any meaningful way, and these types of cases will require creativity and innovation "on the fly." I will describe three cases, which are examples of each of these situations, with suggestions on how to handle each type of situation optimally. I will describe the preparation, such as it was for each, in some detail to help the reader understand how it felt to deal with each of these cases. The technical details of each of these cases resulted in a publication, which will be cited in the references, should the reader want to learn more about them. PMID- 27355145 TI - Pannus Formation Leads to Valve Malfunction in the Tricuspid Position 19 Years after Triple Valve Replacement. AB - The Medtronic ATS Open Pivot mechanical valve has been successfully used in heart valve surgery for more than two decades. We present the case of a patient who, 19 years following a tricuspid valve replacement with an ATS prosthesis as part of a triple valve operation following infective endocarditis, developed severe tricuspid regurgitation due to pannus formation. PMID- 27355146 TI - Early-Term Outcomes for Treatment of Saphenous Vein Insufficiency with N-Butyl Cyanoacrylate: A Novel, Non-Thermal, and Non-Tumescent Percutaneous Embolization Technique. AB - BACKGROUND: The purpose of this study was to present early-term outcomes of VariClose(r) Vein Sealing System, which is a novel, non-thermal, and non tumescent percutaneous embolization technique for treatment of saphenous vein insufficiency. METHODS: Between March 2014 and July 2015, 189 saphenous veins in 141 patients were treated with Variclose Vein Sealing System containing n-butyl cyanoacrylate. Pre-, intra-, post-procedural, and follow-up data of patients were collected and retrospectively reviewed. RESULTS: Mean age of patients was 42.5 +/ 14.0 years, of which 53% were female. Technical success rate of intervention was 98.9%. Mean procedure time was 14.3 +/- 7.5 minutes. Eighty-nine percent of patients (n = 126/141) were available at mean follow-up time of 6.7 months. Mean Venous Clinical Severity Score was significantly improved from 8.3 +/- 2.2 at pre procedure period to 3.3 +/- 1.8 at follow-up. No complete recanalization was observed, but 2 patients were presented with partial recanalization during follow up. The complete occlusion rate was 98.4%. No serious adverse event related to procedure was observed. CONCLUSION: Variclose Vein Sealing System appears to be safe and effective in treatment of saphenous vein insufficiency. Further randomized studies with long-term outcomes are required for determining optimal treatment modality in patients with saphenous vein insufficiency. PMID- 27355147 TI - Preoperative Low Serum Albumin Levels Increase the Requirement of Renal Replacement Therapy after Cardiac Surgery. AB - BACKGROUND: Acute kidney injury is a common complication of cardiac surgery that increases morbidity and mortality. The aim of the present study is to analyze the association of preoperative serum albumin levels with acute kidney injury and the requirement of renal replacement therapy after isolated coronary artery bypass graft surgery (CABG). METHODS: We retrospectively reviewed the prospectively collected data of 530 adult patients who underwent isolated CABG surgery with normal renal function. The perioperative clinical data of the patients included demographic data, laboratory data, length of stay, in-hospital complications and mortality. The patient population was divided into two groups: group I patients with preoperative serum albumin levels <3.5 mg/dL; and group II pateints with preoperative serum albumin levels >=3.5 mg/dL. RESULTS: There were 413 patients in group I and 117 patients in group II. Postoperative acute kidney injury (AKI) occured in 33 patients (28.2%) in group I and in 79 patients (19.1%) in group II. Renal replacement therapy was required in 17 patients (3.2%) (8 patients from group I; 9 patients from group II; P = .018). 30-day mortality occurred in 18 patients (3.4%) (10 patients from group I; 8 patients from group II; P = .037). Fourteen of these patients required renal replacement therapy. Logistic regression analysis revealing the presence of lower serum albumin levels preoperatively was shown to be associated with increased incidence of postoperative AKI (OR: 1.661; 95% CI: 1.037-2.661; P = .035). Logistic regression analysis also revealed that DM (OR: 3.325; 95% CI: 2.162-5.114; P = .000) was another independent risk factor for AKI after isolated CABG. CONCLUSION: Low preoperative serum albumin levels result in severe acute kidney injury and increase the rate of renal replacement therapy and mortality after isolated CABG. PMID- 27355148 TI - LVAD as a Bridge to Heart Transplantation in a Patient with Left Ventricular Noncompaction Cardiomyopathy and Advanced Heart Failure. AB - Left ventricular noncompaction cardiomyopathy (LVNC) is a rare hereditary cardiomyopathy characterized by the formation of an outer compacted and inner noncompacted layer of the myocardium. The latter is characterized by prominent trabeculations and deep intertrabecular recesses and is functionally inferior to the compacted myocardium. As there is no specific treatment for patients with LVNC who develop heart failure, the management of these patients is limited and many patients progress to advanced stages of the disease. For LVNC patients with advanced heart failure, the data regarding the use of mechanical circulatory support are scarce. We report a case of a 29-year-old patient with LVNC and advanced refractory heart failure, who was successfully bridged to heart transplantation using a long-term continuous-flow left ventricular assist device. PMID- 27355149 TI - Long-Term Outcome of Intra-Myocardial Injection of Autologous Bone Marrow Mononuclear Cells Combined with Isolated Coronary Artery Bypass Grafting for Patients with Chronic Ischemic Heart Failure. AB - OBJECTIVE: This study aimed to investigate whether intra-myocardial injection of autologous bone marrow mononuclear cells (aBMMNCs) into peri-scarred myocardium during coronary artery bypass grafting (CABG) improved the long-term outcome compared with CABG alone. METHODS: From April 2011 to December 2012, 33 patients with chronic ischemic heart failure were randomly assigned to undergo CABG (control group) or CABG combined with intra-myocardial injection of aBMMNCs (treatment group). The primary endpoints of the study were the changes of left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV) from baseline to six month and two-year follow-up, respectively. The secondary endpoints were the changes of III and IV NYHA classification, 6-minute walk test, B-type natriuretic peptide (BNP) from baseline to follow-up, and major adverse cardiovascular events (MACES) during the follow-up. RESULTS: No patient died and no severe surgical complication occurred perioperatively in either group. The mean number of transplanted aBMMNCs was 98.5 +/- 48.3*106 per patient. The follow-up was completed at six months and 24 months postoperatively. No major transplant related adverse events were detected during the study. The patients in the treatment group had more significant improvement in LVEF than in the control group at six-month follow-up (8.17% versus 4.71%, P = .020), but this benefit was not found at 24-month follow-up (7.44% versus 5.69%, P = .419). There was no significant difference in changes of LVEDV, LVESV, III and IV NYHA classification, 6-minute walk distance, BNP, and MACES between the two groups all through the study. CONCLUSION: Intra-myocardial injection of aBMMNC transplantation on arrested heart during CABG is a safe procedure based on a longer period observation. The patients with chronic ischemic heart failure can benefit from aBMMNCs transplantation in the short-term (6 months) demonstrated by improved global LVEF compared with the control group; however, this additional benefit dimed with time as showed by 24-month clinical and echocardiographic follow-up results. PMID- 27355150 TI - Comparison of Isolated Primary CABG in Two Successive Decades in Patients Under 40 Years of Age. AB - BACKGROUND: Coronary artery bypass graft (CABG) surgery is rarely performed in very young patients. The purpose of our study is to compare the characteristics, treatments, in-hospital, and long-term outcomes of two groups of patients less than 40 years of age who had CABG in two successive decades: 1990-2000 and 2001 2011. METHODS: We identified 145 consecutive patients who underwent primary isolated CABG. Group 1 consisted of 78 patients operated between 1990-2000 and group 2 consisted of 67 patients operated between 2001-2011. Composite end point assessed at follow-up period involved death or recurrence of symptoms, which we defined as myocardial infarction, a need for percutaneous coronary intervention (PCI), reoperation, or congestive heart failure (CHF). RESULTS: Smoking and hypercholesterolemia before CABG were noted as more frequent in group 1 than in group 2: 96.1% versus 83.6%, P = .011; 88.5% versus 61.2%, P = .0001, respectively. Patients from group 2 more frequently received one graft (29.8% versus 11.5%, P = .0059), were operated with off-pump (41.8% versus 0%, P < .0001) or MIDCAB (28.4% versus 0%, P = .0008) techniques, and had complete arterial revascularization (58.2% versus 23.1%, P < .0001). Group 1 patients had a higher prevalence of composite end point (33.9% versus 17.9%, P = .035), with no significant difference in mortality (11.5% versus 10.4%, P = .83). CONCLUSION: Patients operated between 1990-2000 had a higher prevalence of smoking and hypercholesterolemia and higher frequency of composite-end point during folow-up period without significant difference in mortality. PMID- 27355151 TI - Acute Changes in Left Ventricular End Diastolic Pressure following the Transcatheter Closure of an Atrial Septal Defect in Adults. AB - BACKGROUND: Acute changes in left ventricular diastolic function shortly after ASD closure in elderly patients have not been well known. We aimed to investigate acute changes in left ventricular end diastolic pressure (LVEDP) in elderly patients following transcatheter closure of atrial septal defect (ASD). METHODS: All 19 adults with ASDs who underwent transcatheter closure between June 2013 and December 2014 were enrolled. LVEDP was measured prior to device closure and compared with that immediately following device closure and 15 minutes after device closure. RESULTS: The median age of the patients was 48 years old. The baseline E/e' and LVEDP values were 8.3 +/- 2.8 and 13 +/- 3 mmHg. The LVEDP value immediately following closure was 19 +/- 4 mmHg, and 15 minutes after closure was 16 +/- 4 mmHg. The median increase in the LVEDP value immediately following closure was 6 mmHg, which significantly differed from that prior to closure. The LVEDP 15 minutes after closure decreased but remained significantly higher than the value observed immediately after closure. No significant changes were observed with regard to E/e' at either 1 day or 3 months following closure. The LVEDP value 15 minutes after device closure was significantly correlated with those observed before closure and immediately following closure; however, no significant correlations were observed with regard to patient age, Qp/Qs, E/e' before closure, or E/e' 3 months after device closure. CONCLUSION: LVEDP in adults with ASDs significantly increases following device closure. LVEDP before closure predicts LVEDP following device closure. PMID- 27355152 TI - A comprehensive study of serum odd- and branched-chain fatty acids in patients with excess weight. AB - OBJECTIVE: While small amounts of odd-chain fatty acids (OCFAs) and branched chain fatty acids (BCFAs) were known to be present in mammals, it was quite recently that they were shown to play an important role in human health. However, still little is known on OCFA and BCFA profiles in subjects who have obesity. The aim of this study was to verify whether obesity is associated with changes in serum OCFA and BCFA profiles. METHODS: Serum content of fatty acids was determined by gas chromatography-mass spectroscopy in 23 patients with excess weight and 21 nonobese controls. RESULTS: Six OCFAs and six BCFAs (three iso BCFAs and three anteiso-BCFAs) were found in sera from the examined subjects. Patients with excess weight presented with significantly lower serum iso-BCFA levels than the controls. Total serum content of iso-BCFAs correlated inversely with serum insulin, triglycerides, and 18:1/18:0 desaturation index. Both OCFA and iso-BCFA levels correlated inversely with C-reactive protein concentration. CONCLUSIONS: Lower iso-BCFA content in patients with excess weight may be involved in elevation of serum concentration of triglycerides and inflammation. Decreased contents of iso-BCFAs in subjects with have obesity, and established anti-inflammatory, antidiabetic, and anticancer properties of these fatty acids, point to potential beneficial effects of an iso-BCFA-rich diet. PMID- 27355154 TI - Erratum. PMID- 27355153 TI - Miniaturized modules for light sheet microscopy with low chromatic aberration. AB - Two miniaturized fibre-coupled modules for light sheet-based microscopy are described and compared with respect to image quality, chromatic aberration and beam alignment. Whereas in one module the light sheet is created by an achromatic cylindrical lens, reflection by a spherical mirror and concomitant astigmatic distortion are used to create the light sheet in the second module. Test experiments with fluorescent dyes in solution and multicellular tumour spheroids are reported, and some details on construction are given for both systems. Both modules are optimized for imaging individual cell layers of 3D biological samples and can be adapted to fit commercial microscopes. PMID- 27355155 TI - Probing the rheological properties of supported thin polystyrene films by investigating the growth dynamics of wetting ridges. AB - Despite its importance in the processing of nanomaterials, the rheological behavior of thin polymer films is poorly understood, partly due to the inherent measurement challenges. Herein, we have developed a facile method for investigating the rheological behavior of supported thin polymeric films by monitoring the growth of the "wetting ridge"-a microscopic protrusion on the film surface due to the capillary forces exerted by a drop of ionic liquid placed on the film surface. It was found that the growth dynamics of the wetting ridge and the behavior of polystyrene rheology are directly linked. Important rheological properties, such as the flow temperature (Tf), viscosity (eta), and terminal relaxation time (tau0) of thin polystyrene films, can be derived by studying the development of the height of the wetting ridge with time and the sample temperature. Rheological studies using the proposed approach for supported thin polystyrene (PS) films with thickness down to 20 nm demonstrate that the PS thin film exhibits facilitated flow, with reduced viscosity and lowered viscous temperature and a shortened rubbery plateau, when SiOx-Si was used as the substrate. However, sluggish flow was observed for the PS film supported by hydrogen-passivated silicon substrates (H-Si). The differences in enthalpic interactions between PS and the substrates are the reason for this divergence in the whole-chain mobility and flow ability of thin PS films deposited on SiOx-Si and H-Si surfaces. These results indicate that this approach could be a reliable rheological probe for supported thin polymeric films with different thicknesses and various substrates. PMID- 27355156 TI - Vascular access in neonates. AB - The aim of this review was to provide updated and recent literature on vascular access in neonates in order to help neonatologists in their clinical practice, using as data sources textbooks, recent published articles from Pubmed, Cochrane reviews and web guidelines. PMID- 27355157 TI - The role of very low birth weight and prematurity on cardiovascular disease risk and on kidney development in children: a pilot study. AB - BACKGROUND: Cardiovascular and renal disease are nowadays among the leading cause of morbidity and mortality in Western Countries. Low birth weight has been recently considered a key factor in determining cardiovascular disease and long term renal disease in adulthood. METHODS: In our study we analyzed, through echocardiography, eco color Doppler of carotid arteries, ultrasound of abdominal aorta and kidneys, morphological characteristics of cardiovascular and renal system, in a in a group of children born preterm with very low birth weight, (birth weight<1500 grams) and in a group of children, age and sex matched, born at term with weight appropriate for gestational age. 15 children born very low birth weight preterm (cases), aged from 3 to 5 years, and 15, age and sex matched children, born appropriate for gestational age at term (controls) were enrolled in the study. RESULTS: The two groups were homogeneous for interventricular septum diameter, left ventricular end-systolic diameter, left atrial diameter, and ejection fraction. Left ventricular end diastolic diameter was higher in case compared to controls (p=0.04), while aortic diameter root smaller (p=0.005). E and A waves peak velocities and E/A ratio resulted lower in cases compared to controls (p=0.02, p<0.001and p <0.001, respectively). Tei index, S, e' and a' waves velocities were similar in the two groups, while E/e' ratio was higher in cases (p=0.046). Intima-media thickness and antero-posterior diameter of abdominal aorta values did not differ in cases versus controls. Longitudinal diameters of both kidneys were reduced in cases compared to controls (p <0.05). CONCLUSIONS: Although limited by the small sample size, our study highlighted an increased size of the left ventricle and altered left ventricular diastolic function in children born very low birth weight preterm, but no long term consequences on systolic performance and vascular structure have been found. The finding of smaller kidneys in ex-preterm very low birth weight children could explain their higher susceptibility to develop renal disease in adulthood. PMID- 27355158 TI - Growth hormone receptor polymorphisms and growth hormone response to stimulation test: a pilot study. AB - BACKGROUND: No gold standard pharmacological stimulation test exists for the diagnosis of growth hormone deficiency (GHD). In addition, the genetic factors that influence growth hormone (GH) responses remain unclear. This study aimed to determine whether polymorphisms in exon 6 of the GH receptor gene influence responses to the L-arginine GH stimulation test. METHODS: This study included 27 prepubertal patients with confirmed GHD. GHD was defined as a peak GH level <8 ng/ml in response to pharmacological stimulation. The mean GH peak after L arginine stimulation was 2.9 +/- 2.9 ng/ml. RESULTS: The included patients had the following genotypes at the third position of codon 168: AA (n=1), AG (n=15) and GG (n=11). Patients carrying the AA and AG genotypes exhibited stronger responses to arginine than patients with the GG genotype (3.1 +/- 2.7 vs. 1.5 +/- 1.3 ng/ml, p = 0.01). CONCLUSION: The approach employed in this study could elucidate GH profiles under physiological and pathological conditions, facilitating improved interpretation of pharmacological stimulation tests. PMID- 27355159 TI - Recognizing potential barriers to setting and achieving effective rehabilitation goals for patients with persistent pain. AB - Although the process of goal setting in rehabilitation of individuals with persistent pain is considered a fundamental and requisite skill, it is frequently reported as a challenging element of clinical practice. Factors which may contribute to the complexity of goal setting include the potential for unrecognized shifts in cognitive function, psychological comorbidities, and the social context of both providers and patients. This review aims to describe factors which may confound the process of setting and achieving collaborative rehabilitation goals using a biopsychosocial framework and to provide recommendations to enhance goal setting effectiveness. PMID- 27355160 TI - Strengthening of polymer ordered porous materials based on a layered nanocomposite internal structure. AB - Ordered porous polymeric films attract more and more attention because they have many advantages and broad application prospects in many fields. But because of their large flexibility and poor mechanical properties, some of the scope for application is greatly limited. Inspired by the ordered pore structure of the honeycomb and the layered structure of natural nacre, we prepared an ordered porous polymer film with a layered structure in the pore wall by the solvent evaporation-restriction assisted hard template method. Compared with other samples, this kind of film with the layered structure showed both excellent mechanical properties and good stability. This kind of film with high mechanical strength, is considered to have wide applications in the areas of separation, biomedicine, precision instruments, aerospace, environmental protection and so on. PMID- 27355161 TI - How photon pump fluence changes the charge carrier relaxation mechanism in an organic-inorganic hybrid lead triiodide perovskite. AB - This study explores the excitation wavelength and fluence dependence of processes occurring in formamidinium lead triiodide (FAPbI3) film using time-resolved transient absorption and terahertz spectroscopies. The results indicate that second-order processes are responsible for charge carrier recombination at low fluences of the absorbed photons (below 8.4 * 1012 ph per cm2). An increase in fluence leads to the appearance and successive reduction of the time component assigned to the Auger recombination of free charge carriers (240-120 ps). Simultaneously, the bimolecular recombination time decreases from ~1400 to ~700 ps. Further increasing the pump fluence produces an exciton population that recombines in 6 ps. The comparison of two characteristic bleaching bands located at 480 and 775 nm provides evidence for the validity of the two valence bands model. Excitation with higher fluences results in a marked difference in the probed dynamics at these bands, reflecting the action of two excited states at the conduction band. Our results demonstrate that a single model cannot be applied in characterizing the perovskite absorber transitions at all pump fluences. These findings are relevant in understanding their operating mechanism under specific experimental conditions, which should differ for perovskite based solar cells, lasing media or photon detectors. PMID- 27355162 TI - Neutron emission and dose distribution from natural carbon irradiated with a 12 MeV amu-1 12C5+ ion beam. AB - Measured neutron energy distribution emitted from a thick stopping target of natural carbon at 0 degrees , 30 degrees , 60 degrees and 90 degrees from nuclear reactions caused by 12 MeV amu-1 incident 12C5+ ions were converted to energy differential and total neutron absorbed dose as well as ambient dose equivalent H *(10) using the fluence-to-dose conversion coefficients provided by the ICRP. Theoretical estimates were obtained using the Monte Carlo nuclear reaction model code PACE and a few existing empirical formulations for comparison. Results from the PACE code showed an underestimation of the high energy part of energy differential dose distributions at forward angles whereas the empirical formulation by Clapier and Zaidins (1983 Nucl. Instrum. Methods 217 489-94) approximated the energy integrated angular distribution of H *(10) satisfactorily. Using the measured data, the neutron doses received by some vital human organs were estimated for anterior-posterior exposure. The estimated energy averaged quality factors were found to vary for different organs from about 7 to about 13. Emitted neutrons having energies above 20 MeV were found to contribute about 20% of the total dose at 0 degrees while at 90 degrees the contribution was reduced to about 2%. PMID- 27355163 TI - More flexible approaches are needed to improve cardiac rehabilitation. PMID- 27355164 TI - Funding New Zealand's public healthcare system: time for an honest appraisal and public debate. AB - Successive New Zealand governments have claimed that the cost of funding the country's public healthcare services is excessive and unsustainable. We contest that these claims are based on a misrepresentation of healthcare spending. Using data from the New Zealand Treasury and the Organisation for Economic Cooperation and Development (OECD), we show how government spending as a whole is low compared with most other OECD countries and is falling as a proportion of GDP. New Zealand has a modest level of health spending overall, but government health spending is also falling as a proportion of GDP. Together, the data indicate the New Zealand Government can afford to spend more on healthcare. We identify compelling reasons why it should do so, including forecast growing health need, signs of increasing unmet need, and the fact that if health needs are not met the costs still have to be borne by the economy. The evidence further suggests it is economically and socially beneficial to meet health needs through a public health system. An honest appraisal and public debate is needed to determine more appropriate levels of healthcare spending. PMID- 27355165 TI - Dispensing data captures individual-level use of aspirin for cardiovascular disease prevention, despite availability over-the-counter. AB - AIM: To assess the level of agreement in aspirin use measured by self-report and dispensing data. METHOD: We assessed preventive cardiovascular medication use (prescription-only statins and blood pressure-lowering therapy; and aspirin-also available over-the-counter) at baseline in participants in the New Zealand IMPACT trial for whom these medications were prescribed by their general practitioner. A trial nurse not involved in their ongoing health care obtained participants' self reported aspirin use data. We obtained dispensing data from the national pharmaceutical dispensing database and assessed agreement between the two measures using kappa coefficients. RESULTS: Of the 513 trial participants, 36% were women, 50% were of Maori ethnicity, and 45% had a history of cardiovascular disease. The level of agreement between self-reported aspirin use and dispensing data was substantial (kappa 0.75, 95% CI 0.69 to 0.82). The level of agreement in aspirin use measured by these two sources of data was similar to that for statin and blood pressure-lowering therapy use, for all participants combined, for subgroups according to ethnicity (Maori and non-Maori) and history of cardiovascular disease. CONCLUSIONS: Despite its availability over-the-counter, aspirin use in patients for whom cardiovascular medications are indicated can be assessed accurately from dispensing data. PMID- 27355166 TI - Antimicrobial stewardship using pharmacy data for the nurse-led school-based clinics in Counties Manukau District Health Board for management of group A streptococcal pharyngitis and skin infection. AB - AIM: To evaluate antimicrobial usage in the school-based clinics against operating guidelines. METHOD: Antimicrobial prescribing data (2014) from 10/18 participating pharmacies serving 14,153/23,588 primary school children of the programme were accessible. Prescriptions from 5/10 pharmacies were available for identifying type, amount, and indication of the medicine. One pharmacy serving a defined population (n=3,513) with single healthcare provider delivering the school programme was selected for detailed evaluation and identifying individuals receiving multiple treatments. RESULTS: Data from 10 pharmacies (n=7,889 prescriptions) showed 91.2% of prescriptions were for group A streptococcal positive throat swab, 8.8% for skin infections. More detail from 5/10 pharmacies showed only 2% of group A streptococcal pharyngitis treatments (107/4,672) were not first-line (56 cephalexin and 51 rifampin prescriptions). Fusidic acid (159/452, 35.18%) or cephalexin (169/452, 37.39%) were most commonly used for skin infection. Analysis in the defined population showed <4% (151/4,325) of assessed skin conditions received antimicrobials, and only 6 individuals received more than one course of oral antimicrobial over the year. CONCLUSION: Antimicrobial administration demonstrates high compliance with the protocol. There was very limited use of second-line antimicrobials for recurrent pharyngitis. Most skin infections did not require antimicrobial treatment. Repeated antimicrobials for individuals were rare. PMID- 27355167 TI - Pharmacological therapy following acute coronary syndromes in patients with atrial fibrillation: how do we balance ischaemic risk with bleeding risk? AB - BACKGROUND: Dual anti-platelet therapy (DAPT) with aspirin and a P2Y12receptor antagonist is standard of care following an acute coronary syndrome (ACS), as it has been shown to reduce recurrent myocardial infarction (MI) and death. In atrial fibrillation (AF) patients, the use of oral anticoagulants (OACs) is the standard of care as these agents have been shown to reduce the risk of stroke and death. Current guidelines suggest that decisions around antithrombotic therapy should be made by assessing ischaemic and bleeding risks. The aim of this study was to examine current pharmacotherapy of AF inpatients with ACS. METHODS: We prospectively enrolled ACS patients being managed invasively with a medical history of AF, or those in AF during admission ECG, from the pre-existing Wellington ACS registry. Enrolment criteria included pre-treatment on DAPT. Demographics, clinical characteristics, management, in-hospital outcomes and discharge medications were recorded. RESULTS: At discharge, only 11.8% of AF patients were prescribed an OAC and this was not related to risk of stroke (CHA2DS2-VASc score), bleeding (CRUSADE score) or any other clinical characteristics. However, discharge OAC use was associated with whether the patient was treated with an OAC at admission (OR 14, CI 3.4-58, p=0.001). DAPT was the default discharge treatment and occurred in 72% of AF patients. A moderate correlation between stroke risk and bleeding risk was identified (rs=0.68, p=0.01). A group of 44 (47%) patients were identified who were at high risk of stroke (CHA2DS2-VASc >=2) and low risk of bleeding (CRUSADE score <=30). CONCLUSION: At discharge we observed a very low rate of OAC prescription. Despite most AF patients being high risk for stroke, DAPT was the preferred treatment option. Our data suggests there is a group of patients with high stroke risk and relatively low bleeding risk, in who OAC use may be appropriate. Developing a guideline to assist clinicians in targeting this group of patients may help improve outcomes in AF patients following MI. PMID- 27355168 TI - A national survey of cardiac rehabilitation services in New Zealand: 2015. AB - AIMS: Guidelines for cardiac rehabilitation (CR) programmes inform best practice. In Aotearoa NewZealand, little information exists about the structure and services provided by CR programmes and there is a poor understanding of how existing CR programmes are delivered with respect to evidence-based national guidelines. METHODS: All 46 CR providers in New Zealand were invited to participate in a national survey in 2015. The survey sought information on the following: unit structure; referral processes; patient assessment; audit (including quality assurance activity); Phase 2 CR content; and support for special populations. Simple descriptive analysis of the responses was conducted, involving forming counts and percentages. RESULTS: Thirty-six distinct units completed the survey and 94% provided Phase 2. Assessment tools, Phase 2 educational components, and the methods of providing the exercise component varied. Most units audited their services, 25% audited their programme six monthly or more frequently. Just over half of the units (56%) reported key performance indicators. CONCLUSIONS: The survey identified variations in delivery and content of CR in New Zealand, with poor understanding of the impact on patient outcomes. This is likely due to the absence of standardised audit practices and routine collection of key performance indicators on a national basis. PMID- 27355169 TI - Medical students: where have they come from; where are they going? AB - AIMS: There remain shortages of doctors in rural areas. This study aimed to describe the location and size of New Zealand medical students' hometowns over the past decade; to document changes in intended practice location between entry and graduation; and to explore the relationship between background and intended location of practice. METHODS: All commencing and graduating students from one New Zealand medical programme from 2006-2015 were invited to complete a career intention survey. Students' reported background and practice location intention at entry were compared with intention at exit. RESULTS: Response rates were 92% for entry and 84% for exit surveys. On average, 21% of medical students were from regional-rural (RR) backgrounds, with no significant change over time (p= 0.4036). Most were admitted via a designated rural entry pathway. Students from RR backgrounds were four times more likely at entry, and nearly three times more likely at exit, to have an RR intention than urban students. Those with an RR intention at entry were three times more likely to have an RR intention at exit than students with an urban intention. CONCLUSION: Medical students from an RR background, or with RR intention at entry to medical school, are more likely to indicate a RR intention upon graduating. Yet students of an urban background with an RR career intention are important to consider. Future research might explore factors which help consolidate RR career choices in both groups. PMID- 27355170 TI - Cardiac rehabilitation in New Zealand-moving forward. AB - Modern guideline-based cardiac rehabilitation provides an evidence-based, cost effective and comprehensive approach to reduce re-infarction and mortality. It offers a multidisciplinary approach to support self-management, improves psychological and social functioning and adherence to recommended life-style changes and medications. The challenge is to broaden uptake of cardiac rehabilitation, increase participation in supervised exercise programs and ensure that healthy behaviours are maintained in the long term. Shared care planning between cardiac rehabilitation specialists and primary health providers could improve long-term adherence by ensuring continuity of care of patients who have completed a Phase 2 cardiac rehabilitation program, either facility or home based. PMID- 27355171 TI - The complexities of designing therapy for Maori living with stroke-related communication disorders. AB - Stroke-related communication disorders can have a substantial impact on Maori whanau (extended family). Timely and appropriate speech-language therapy is required, but there are many challenges in providing this. In this article we discuss the need for a kaupapa Maori approach to speech-language therapy that is designed by Maori for Maori, and undertaken in a Maori way. We report the results of a literature review that revealed a small but significant body of literature describing Maori experiences of stroke, aphasia and speech-language therapy, and evidence that a Maori-specific therapy programme can improve outcomes for people with stroke. We then consider the social and political context that impacts the design and delivery of such an approach. Informed by the literature, we propose a hierarchy of skill and resource acquisition for speech-language therapists, in which they learn why to be culturally safe, how to be culturally safe, and how to interact before creating resources to build relationships, resources for education and for therapy. The creation of a kaupapa Maori speech-language therapy approach should bring together people with stroke, whanau members and service providers to create therapy that crosses sectors and disciplines and acknowledges the wider social and political context. PMID- 27355172 TI - A 'Rottie' appendix. PMID- 27355173 TI - Losartan and amlodipine overdose-Case Report of a patient with anuric renal failure prior to the onset of hypotension. PMID- 27355174 TI - Allied health professionals' perspectives of working with dysphagia in a rural paediatric team. PMID- 27355175 TI - Menevit-the data never seen. PMID- 27355176 TI - Radical cystectomies: a case for prolonged thromboprophylaxis. PMID- 27355177 TI - Defence of the Living Dead: zombies as vectors for transmitting positive health messages. PMID- 27355178 TI - Clinical insignificance of alcohol in salbutamol metered-dose inhalers-it's time to stop flogging the horse. PMID- 27355179 TI - Semantic interference and its control: A functional neuroimaging and connectivity study. AB - During picture naming, the ease with which humans generate words is dependent upon the context in which they are named. For instances, naming previously presented items results in facilitation. Instead, naming a picture semantically related to previous items displays persistent interference effects (i.e., cumulative semantic interference, CSI). The neural correlates of CSI are still unclear and it is a matter of debate whether semantic control, or cognitive control more in general, is necessary for the resolution of CSI. We carried out an event-related fMRI experiment to assess the neural underpinnings of the CSI effect and the involvement and nature of semantic control. Both left inferior frontal gyrus (LIFG) and the left caudate nucleus (LCN) showed a linear increase of BOLD response positively associated with the consecutive number of presentations of semantically related pictures independently of task-load. The generalized psychophysiological interaction analysis showed that LIFG demonstrated a quantitative neural connectivity difference with the left supramarginal and angular gyri for increases of task-load and with the fusiform gyri for linear CSI increases. Furthermore, seed-to-voxel functional connectivity showed that LIFG activity coupled with different regions involved in cognitive control and lexicosemantic processing when semantic interference was elicited to a minimum or maximum degree. Our results are consistent with the lexical competitive nature of the CSI effect, and we provide novel evidence that semantic control lies upon a more general cognitive control network (i.e., LIFG and LCN) responsible for resolving interference between competing semantically related items through connectivity with different brain areas in order to guarantee the correct response. Hum Brain Mapp 37:4179-4196, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27355180 TI - WNT5A and Its Receptors in the Bone-Cancer Dialogue. AB - Wnt signaling is critical for tumorigenesis and skeletal remodeling. However, its contribution to the formation of metastatic bone lesions remains poorly defined. One major challenge of unraveling its role in cancer progression is the high complexity of Wnt signaling, which includes numerous ligands, receptors, and inhibitors, with intricate biological effects and specific signaling pathways depending on the cellular context. In this perspective, we summarize the role of the noncanonical Wnt ligand WNT5A in the development and metastatic process of osteotropic cancer entities. We focus on its tumor-suppressive function in breast cancer, tumor promoting effects in melanoma, and ambiguous role in prostate cancer, and discuss potential challenges and opportunities that may be associated with targeting Wnt signaling for cancer therapy and treatment of bone metastases. (c) 2016 American Society for Bone and Mineral Research. PMID- 27355181 TI - A novel iridium/acid co-catalyzed transfer hydrogenative C(sp(3))-H bond alkylation to access functionalized N-heteroaromatics. AB - A novel iridium/acid co-catalysed transfer hydrogenative coupling strategy, enabling direct alkylation of C(sp(3))-H bonds and atom-economic access to alkyl chain-lengthened N-heteroaromatics from six-membered 2-alkyl cyclic amines and aldehydes, has been demonstrated. This work has built an important basis to convert cyclic amines, a class of bulk chemical raw materials, into functionalized products. PMID- 27355183 TI - Health-related quality of life and burden of disease in chronic pain measured with the 15D instrument. AB - Health-related quality of life (HRQoL) measurement aims to capture the complete, subjective health state of the patients and to comprehensively evaluate treatment outcomes. The aim of this study was to assess, using the 15D HRQoL instrument, HRQoL in a sample of 1528 chronic pain patients, referred to the multidisciplinary pain clinic of the Helsinki University Hospital during 2004 to 2012. The 15D results of the chronic pain patients were compared with those of a matched general population. To analyse the properties of the 15D, the results were compared with the preadmission questionnaire of the pain clinic, containing questions about background factors, aspects of the pain, and its impact on life. The mean 15D score of the chronic pain patients was one of the lowest reported using 15D; 0.710 vs 0.922 in the general population. It equalled the score of advanced cancer patients in palliative care. The 15D scores were normally distributed, and 15D showed both statistically and clinically significant discriminative power in pain-related background factors. Visual analogue scale on pain intensity, visual analogue scale on pain-related distress, and the impact of pain on daily life correlated well with the 15D score. Pain intensity did not have independent predictive value on the score. The results indicate heavy perceived burden of illness in chronic pain patients. In light of the questions analysed, 15D appears sensitive and discriminative in chronic pain patients in tertiary care. Instead of pain intensity, the impaired HRQoL in chronic pain was mainly because of the psychosocial aspects of pain. PMID- 27355184 TI - Psychological interventions in managing postoperative pain in children: a systematic review. AB - Pediatric surgeries are common and painful for children. Postoperative pain is commonly managed with analgesics; however, pain is often still problematic. Despite evidence for psychological interventions for procedural pain, there is currently no evidence synthesis for psychological interventions in managing postoperative pain in children. The purpose of this review was to assess the efficacy of psychological interventions for postoperative pain in youth. Psychological interventions included Preparation/education, distraction/imagery, and mixed. Four databases (PsycINFO, PubMed, EMBASE, and Certified Index to Nursing and Allied Health Literature) were searched to July 2015 for published articles and dissertations. We screened 1401 citations and included 20 studies of youth aged 2 to 18 years undergoing surgery. Two reviewers independently screened articles, extracted data, and assessed risk of bias. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using RevMan 5.3. Fourteen studies (1096 participants) were included in meta-analyses. Primary outcome was pain intensity (0-10 metric). Results indicated that psychological interventions as a whole were effective in reducing children's self reported pain in the short term (SMD = -0.47, 95% CI = -0.76 to -0.18). Subgroup analysis indicated that distraction/imagery interventions were effective in reducing self-reported pain in the short term (24 hours, SMD = -0.63, 95% CI = 1.04 to -0.23), whereas preparation/education interventions were not effective (SMD = -0.27, 95% CI = -0.61 to 0.08). Data on the effects of interventions on longer term pain outcomes were limited. Psychological interventions may be effective in reducing short-term postoperative pain intensity in children, as well as longer term pain and other outcomes (eg, adverse events) require further study. PMID- 27355182 TI - Prior voluntary wheel running attenuates neuropathic pain. AB - Exercise is known to exert a systemic anti-inflammatory influence, but whether its effects are sufficient to protect against subsequent neuropathic pain is underinvestigated. We report that 6 weeks of voluntary wheel running terminating before chronic constriction injury (CCI) prevented the full development of allodynia for the ~3-month duration of the injury. Neuroimmune signaling was assessed at 3 and 14 days after CCI. Prior exercise normalized ipsilateral dorsal spinal cord expression of neuroexcitatory interleukin (IL)-1beta production and the attendant glutamate transporter GLT-1 decrease, as well as expression of the disinhibitory P2X4R-BDNF axis. The expression of the macrophage marker Iba1 and the chemokine CCL2 (MCP-1), and a neuronal injury marker (activating transcription factor 3), was attenuated by prior running in the ipsilateral lumbar dorsal root ganglia. Prior exercise suppressed macrophage infiltration and/or injury site proliferation, given decreased presence of macrophage markers Iba1, iNOS (M1), and Arg-1 (M2; expression was time dependent). Chronic constriction injury-driven increases in serum proinflammatory chemokines were suppressed by prior running, whereas IL-10 was increased. Peripheral blood mononuclear cells were also stimulated with lipopolysaccharide ex vivo, wherein CCI-induced increases in IL-1beta, nitrite, and IL-10 were suppressed by prior exercise. Last, unrestricted voluntary wheel running, beginning either the day of, or 2 weeks after, CCI, progressively reversed neuropathic pain. This study is the first to investigate the behavioral and neuroimmune consequences of regular exercise terminating before nerve injury. This study suggests that chronic pain should be considered a component of "the diseasome of physical inactivity," and that an active lifestyle may prevent neuropathic pain. PMID- 27355186 TI - VISION LOSS IN A PATIENT WITH PRIMARY PULMONARY HYPERTENSION AND LONG-TERM USE OF SILDENAFIL. AB - PURPOSE: To describe a case of bilateral, asymmetrical outer macular atrophy in a patient with pulmonary hypertension treated with long-term sildenafil (Revatio). METHODS: Case report with fundus photography, spectral domain optical coherence tomography, fundus autofluorescence, and fluorescein angiography imaging. RESULTS: A 32-year-old African American woman with a history of primary pulmonary hypertension and 5-year history of oral sildenafil (Revatio) use presented with decreasing central vision in her left eye. She reported a decline in central vision in the left eye that started 1 month after treatment initiation and progressed until discontinuation 5 years later. Visual acuity was 20/20 in the right eye and 20/100 in the left eye. Fundus photography revealed retinal pigment epithelial mottling and atrophy in the right eye and parafoveal retinal pigment epithelial mottling and atrophy in a ring-like configuration of the left eye. Optical coherence tomography demonstrated outer retinal irregularity in the right eye and disrupted outer retina involving the external limiting membrane, inner segment/outer segment junction, and the retinal pigment epithelium in the left eye; no choroidal thickening was observed. Fundus autofluorescence showed mild hypoautofluorescence in the foveal center with an irregular autofluorescence pattern in the parafovea of the left eye. Fluorescein angiography revealed capillary dropout with pinpoint hyperfluorescence and leakage in the far periphery bilaterally. A window defect was also observed in the foveal center of the left eye. CONCLUSION: Sildenafil and other PDE5 inhibitors have been associated with several ocular side effects. However, this is the first report in the literature of outer macular atrophy in a patient with pulmonary hypertension and long-term use of oral sildenafil. All patients with long-term use of sildenafil should be educated on the risk of potential visual adverse effects. PMID- 27355188 TI - Zoledronic Acid Improves Bone Quality in the Streptozotocin-Induced Diabetes Rat through Affecting the Expression of the Osteoblast-Regulating Transcription Factors. AB - Aims: To evaluate the short term effect of zoledronic acid on bone remodeling in the streptozotocin induced diabetes rats. Materials and Methods: Diabetes was induced by an injection of streptozotocin (60 mg/kg). The rats were treated with zoledronic acid (0.1 mg/kg) at the onset of diabetes (Z-I group) and 2 weeks later (Z-II group). Rats were sacrificed at the 1, 2, 3, 4 and 5 weeks after the onset of diabetes. Real-time PCR and western blot were performed to detect the expression of the following osteogenic gene mRNAs and their proteins: bone morphogenetic proteins 2 (BMP2), Runx2, Osterix and Noggin. The bone mineral density (BMD) and the mechanical resistance test was measured. Results: BMP2, Runx2 and Osterix mRNA and protein expression in group D had regulated down, while Noggin expression increased. Z-I treatment could reverse the results. However group Z-II showed only a transient reversing effect. On the 5th week in group D, the BMD decreased, the bone trabecular distance increased, while the trabecular thickness and bone trabecular volume were reduced, the biomechanics index decreased significantly. Zoledronic acid treatment restored these alterations. Conclusions: Zoledronic acid administered in the early stage of the diabetes could prevent the osteopenia. The underlying mechanisms might be that zoledronic acid treatment reversed the effect of diabetes on the expression of osteoblast-regulating transcription factors: BMP2, Runx2 and Osterix. PMID- 27355187 TI - Opioids for restless legs syndrome. AB - BACKGROUND: Restless legs syndrome (RLS) is a distressing and common neurological disorder that may have a huge impact in the quality of life of those with frequent and intense symptoms. Patients complain of unpleasant sensations in the legs, at or before bedtime, and feel an urge to move the legs, which improves with movement, such as walking. Symptoms start with the patient at rest (e.g. sitting or lying down), and follow a circadian pattern, increasing during the evening or at night. Many pharmacological intervention are available for RLS, including drugs used to treat Parkinson's disease (L-Dopa and dopaminergic agonists), epilepsy (anticonvulsants), anxiety (benzodiazepines), and pain (opioids). Dopaminergic drugs are those most frequently used for treatment of RLS, but some patients do not respond effectively and require other medication. Opioids, a class of medications used to treat severe pain, seem to be effective in treating RLS symptoms, and are recommended for patients with severe symptoms, because RLS and pain appear to share the same mechanism in the central nervous system. All available drugs are associated to some degree with side effects, which can impede treatment. Opioids are associated with adverse events such as constipation, tolerance, and dependence. This justifies the conduct of a systematic review to ascertain whether opioids are safe and effective for treatment of RLS. OBJECTIVES: To asses the effects of opioids compared to placebo treatment for restless legs syndrome in adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled trials, CENTRAL 2016, issue 4 and MEDLINE, EMBASE, and LILACS up to April 2016, using a search strategy adapted by Cochraneto identify randomised clinical trials. We checked the references of each study and established personal communication with other authors to identify any additional studies. We considered publications in all languages. SELECTION CRITERIA: Randomised controlled clinical trials of opioid treatment in adults with idiopathic RLS. DATA COLLECTION AND ANALYSIS: Two review authors independently screened articles, independently extracted data into a standard form, and assessed for risk of bias. If necessary, they discussed discrepancies with a third researcher to resolve any doubts. MAIN RESULTS: We included one randomised clinical trial (N = 304 randomised; 204 completed; 276 analysed) that evaluated opioids (prolonged release oxycodone/naloxone) versus placebo. After 12 weeks, RSL symptoms had improved more in the drug group than in the placebo group (using the IRLSSS: MD -7.0; 95% CI -9.69 to -4.31 and the CGI: MD -1.11; 95% CI 1.49 to -0.73). More patients in the drug group than in the placebo group were drug responders (using the IRLSSS: RR 1.82; 95% CI 1.37 to 2.42 and the CGI: RR1.92; 95% ICI 1.49 to 2.48). The proportion of remitters was greater in the drug group than in the placebo group (using the IRLSSS: RR 2.14; 95% CI 1.45 to 3.16). Quality of life scores also improved more in the drug group than in the placebo group (MD -0.73; 95% CI -1.1 to -0.36). Quality of sleep was improved more in the drug group measured by sleep adequacy (MD -0.74; 95% CI -1.15 to 0.33), and sleep quantity (MD 0.89; 95% CI 0.52 to 1.26).There was no difference between groups for daytime somnolence, trouble staying awake during the day, or naps during the day. More adverse events were reported in the drug group (RR 1.22; 95% CI 1.07 to 1.39). The major adverse events were gastrointestinal problems, fatigue, and headache. AUTHORS' CONCLUSIONS: Opioids seem to be effective for treating RLS symptoms, but there are no definitive data regarding the important problem of safety. This conclusion is based on only one study with a high dropout rate (moderate quality evidence). PMID- 27355189 TI - Serum Paraoxonase-1 Levels are Significantly Decreased in the Presence of Insulin Resistance. AB - Paraoxonase-1 (PON1) is an extracellular esterase contributing to the anti atherogenic and anti-inflammatory properties of HDL and has a protective role in the progression of atherosclerosis. The aim of the present study was to compare serum paraoxonase-1 levels between obese subjects with prediabetes and normal glucose tolerance. METHODS: In this study were included 76 patients with mean age 50.7+/-10.7 years, divided into 2 age and BMI-matched groups - group 1 with obesity without glycemic disturbances (n=38) and group 2 with prediabetes (n=38). Oral glucose tolerance test (OGTT) with measurement of immunoreactive insulin was performed in all participants and levels of PON1 were measured using ELISA method. RESULTS: There was only a tendency towards higher PON1 levels in patients with prediabetes compared to controls. However, individuals with insulin resistance had significantly lower levels of PON1 compared to those without. The levels of PON1 showed a negative correlation with the blood glucose on 120th minute of OGTT, fasting IRI, HOMA index, BMI, WSR, WHR and particularly with waist circumference and positive with HDL-cholesterol. CONCLUSIONS: The levels of PON1 are similar in patients with and wthout prediabetes, but are significantly decreased in patients with insulin resistance and correlate with anthropometric markers of visceral adiposity. PMID- 27355190 TI - Diagnosis of Diabetes Mellitus by Extraction of Morphological Features of Red Blood Cells Using an Artificial Neural Network. AB - Background and Aim: Diabetes mellitus is a metabolic disorder characterized by varying hyperglycemias either due to insufficient secretion of insulin by the pancreas or improper utilization of glucose. The study was aimed to investigate the association of morphological features of erythrocytes among normal and diabetic subjects and its gender-based changes and thereby to develop a computer aided tool to diagnose diabetes using features extracted from RBC. Materials and Methods: The study involved 138 normal and 144 diabetic subjects. The blood was drawn from the subjects and the blood smear prepared was digitized using Zeiss fluorescent microscope. The digitized images were pre-processed and texture segmentation was performed to extract the various morphological features. The Pearson correlation test was performed and subsequently, classification of subjects as normal and diabetes was carried out by a neural network classifier based on the features that demonstrated significance at the level of P<0.05. Result: The proposed system demonstrated an overall accuracy, sensitivity, specificity, positive predictive value and negative predictive value of 93.3, 93.71, 92.8, 93.1 and 93.5% respectively. Conclusion: The morphological features exhibited a statistically significant difference (P<0.01) between the normal and diabetic cells, suggesting that it could be helpful in the diagnosis of Diabetes mellitus using a computer aided system. PMID- 27355191 TI - Mutations of Vasopressin Receptor 2 Including Novel L312S Have Differential Effects on Trafficking. AB - Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a genetic disease first described in 2 unrelated male infants with severe symptomatic hyponatremia. Despite undetectable arginine vasopressin levels, patients have inappropriately concentrated urine resulting in hyponatremia, hypoosmolality, and natriuresis. Here, we describe and functionally characterize a novel vasopressin type 2 receptor (V2R) gain-of-function mutation. An L312S substitution in the seventh transmembrane domain was identified in a boy presenting with water-induced hyponatremic seizures at the age of 5.8 years. We show that, compared with wild type V2R, the L312S mutation results in the constitutive production of cAMP, indicative of the gain-of-function NSIAD profile. Interestingly, like the previously described F229V and I130N NSIAD-causing mutants, this appears to both occur in the absence of notable constitutive beta-arrestin2 recruitment and can be reduced by the inverse agonist Tolvaptan. In addition, to understand the effect of various V2R substitutions on the full receptor "life-cycle," we have used and further developed a bioluminescence resonance energy transfer intracellular localization assay using multiple localization markers validated with confocal microscopy. This allowed us to characterize differences in the constitutive and ligand-induced localization and trafficking profiles of the novel L312S mutation as well as for previously described V2R gain-of-function mutants (NSIAD; R137C and R137L), loss-of-function mutants (nephrogenic diabetes insipidus; R137H, R181C, and M311V), and a putative silent V266A V2R polymorphism. In doing so, we describe differences in trafficking between unique V2R substitutions, even at the same amino acid position, therefore highlighting the value of full and thorough characterization of receptor function beyond simple signaling pathway analysis. PMID- 27355192 TI - Glucocorticoids Have Opposing Effects on Liver Fibrosis in Hepatic Stellate and Immune Cells. AB - Liver fibrosis is a reversible wound-healing process that is protective in the short term, but prolonged fibrotic responses lead to excessive accumulation of extracellular matrix components that suppresses hepatocyte regeneration, resulting in permanent liver damage. Upon liver damage, nonparenchymal cells including immune cells and hepatic stellate cells (HSCs) have crucial roles in the progression and regression of liver fibrosis. Here, we report differential roles of the glucocorticoid receptor (GR), acting in immune cells and HSCs, in liver fibrosis. In the carbon tetrachloride hepatotoxin-induced fibrosis model, both steroidal and nonsteroidal GR ligands suppressed expression of fibrotic genes and decreased extracellular matrix deposition but also inhibited immune cell infiltration and exacerbated liver injury. These counteracting effects of GR ligands were dissociated in mice with conditional GR knockout in immune cells (GR(LysM)) or HSC (GR(hGFAP)): the impacts of dexamethasone on immune cell infiltration and liver injury were totally blunted in GR(LysM) mice, whereas the suppression of fibrotic gene expression was diminished in GR(hGFAP) mice. The effect of GR activation in HSC was further confirmed in the LX-2 HSC cell line, in which antifibrotic effects were mediated by GR ligand inhibition of Sma and mad-related protein 3 (SMAD3) expression. We conclude that GR has differential roles in immune cells and HSCs to modulate liver injury and liver fibrosis. Specific activation of HSC-GR without alteration of GR activity in immune cells provides a potential therapeutic approach to treatment of hepatic fibrosis. PMID- 27355193 TI - Minireview: Epigenomic Plasticity and Vulnerability to EDC Exposures. AB - The epigenome undergoes significant remodeling during tissue and organ development, which coincides with a period of exquisite sensitivity to environmental exposures. In the case of endocrine-disrupting compounds (EDCs), exposures can reprogram the epigenome of developing tissues to increase susceptibility to diseases later in life, a process termed "developmental reprogramming." Both DNA methylation and histone modifications have been shown to be vulnerable to disruption by EDC exposures, and several mechanisms have been identified by which EDCs can reprogram the epigenome. These include altered methyl donor availability, loss of imprinting control, changes in dioxygenase activity, altered expression of noncoding RNAs, and activation of cell signaling pathways that can phosphorylate, and alter the activity of, histone methyltransferases. This altered epigenomic programming can persist across the life course, and in some instances generations, to alter gene expression in ways that correlate with increased disease susceptibility. Together, these studies on developmental reprogramming of the epigenome by EDCs are providing new insights into epigenomic plasticity that is vulnerable to disruption by environmental exposures. PMID- 27355196 TI - Rational Molecular Design and Synthesis of Highly Thermo- and Photostable Near Infrared-Absorbing Heptamethine Cyanine Dyes with the Use of Fluorine Atoms. AB - Highly thermo- and photostable, near-infrared-absorbing heptamethine cyanine dyes were achieved with the use of fluorine-containing components. In particular, one prepared heptamethine cyanine dye, bearing a tetrakis(pentafluorophenyl)borate as a counter anion and an N-ethyl-2,2,2-trifluoroacetamido group at the meso position, showed not only a high decomposition temperature (Tdt ), but also very high photostability toward white LED irradiation. PMID- 27355194 TI - Synthesis and Biological Evaluation of N(2) -Substituted 2,4-Diamino-6 cyclohexylmethoxy-5-nitrosopyrimidines and Related 5-Cyano-NNO-azoxy Derivatives as Cyclin-Dependent Kinase 2 (CDK2) Inhibitors. AB - The potent and selective cyclin-dependent kinase 2 (CDK2) inhibitor NU6027 (6 cyclohexylmethoxy-5-nitroso-2,4-diaminopyrimidine) was used as the lead for the synthesis of a series of analogues in order to provide further insight into the structure-activity relationships for 2,4-diaminopyrimidine CDK2 inhibitors. Aliphatic amino substituents were introduced at position 2. The use of linear or less sterically hindered amines gave rise to compounds endowed with slightly better activity than the lead; on the other hand, the compounds were less active if a bulkier amino substituent was used. Substitution of the 5-nitroso group with a 5-cyano-NNO-azoxy moiety afforded a new class of inhibitors, the activity of which against CDK2 was found to be similar to that of the nitroso series. The most active nitroso compound was 8 b ((2S)-2-[(4-amino-6-cyclohexylmethoxy-5 nitrosopyrimidin-2-yl)amino]propan-1-ol; IC50 =0.16 MUm), while in the 5-cyano NNO-azoxy series the most active compound was 9 b (4-amino-5-[(Z)-cyano-NNO azoxy]-2-{[(2S)-1-hydroxypropan-2-yl]amino}-6-cyclohexylmethoxypyrimidine; IC50 =0.30 MUm). Taken together, these new analogues of NU6027 enhance our understanding of the structure-activity relationships for 2,4-diaminopyrimidine CDK2 inhibitors. PMID- 27355197 TI - Analysis of a long-term measurement of air pollutants (2007-2011) in North China Plain (NCP); Impact of emission reduction during the Beijing Olympic Games. AB - Five years measurements were used to evaluate the effect of emission controls on the changes of air pollutants in Beijing and its surroundings in the NCP during 2008 Olympic Games (2008OG). The major challenge of this study was to filter out the effect of variability of meteorological conditions, when compared the air pollutants during the game to non-game period. We used four-year (2007, 2009 2011) average as the Non-2008OG to smooth the temporal variability caused by meteorological parameters. To study the spatial variability and regional transport, 6 sites (urban, rural, a mega city, a heavy industrial city, and a remote site) were selected. The result showed that the annually meteorological variability was significantly reduced. Such as, in BJ the differences between 2008OG and 5-years averaged values were 2.7% for relative humidity and 0.6% for wind speed. As a result, the anomaly of air pollutants between 2008OG and Non 2008OG can largely attribute to the emission control. The comparison showed that the major pollutants (PM10, PM2.5, NO, NOx) at the 6 sites in 2008OG were consistently lowered. For example, PM2.5 in BJ decreased from 75 to 45 MUg/m(3) (40% reduction). However, the emission controls had minor effect on O3 concentrations (1% reduction). In contrast, the O3 precursor (NOx) reduced from 19.7 to 13.2 ppb (33% reduction). The in-sensitivity between NOx and O3 suggested that the O3 formation was under VOCs control condition in NCP, showing that strong VOC emission control is needed in order to significantly reduce O3 concentration in the region. PMID- 27355198 TI - The Effect of Round Window vs Cochleostomy Surgical Approaches on Cochlear Implant Electrode Position: A Flat-Panel Computed Tomography Study. AB - IMPORTANCE: The round window insertion (RWI) and cochleostomy approaches are the 2 most common surgical techniques used in cochlear implantation (CI). However, there is no consensus on which approach is ideal for electrode array insertion, in part because visualization of intracochlear electrode position is challenging, so postoperative assessment of intracochlear electrode contact is lacking. OBJECTIVE: To measure and compare electrode array position between RWI and cochleostomy approaches for CI insertion. DESIGN, SETTING, AND PARTICIPANTS: Retrospective case-comparison study of 17 CI users with Med-El standard-length electrode arrays who underwent flat-panel computed tomography scans after CI surgery at a tertiary referral center. The data was analyzed in October 2015. EXPOSURES: Flat-panel computed tomography scans were collected between January 1 and August 31, 2013, for 22 electrode arrays. The surgical technique was identified by a combination of operative notes and imaging. Eight cochleae underwent RWI and 14 cochleae underwent cochleostomy approaches anterior and inferior to the round window. MAIN OUTCOMES AND MEASURES: Interscalar electrode position and electrode centroid distance to the osseous spiral lamina, lateral bony wall, and central axis of the modiolus. RESULTS: Nine participants were men, and 8, women; the mean age was 54.4 (range, 21-64) years. Electrode position was significantly closer to cochlear neural elements with RWI than cochleostomy approaches. Between the 2 surgical approaches, the RWI technique produced shorter distances between the electrode and the modiolus (mean difference, -0.33 [95% CI, -0.29 to -0.39] mm in the apical electrode; -1.42 [95% CI, -1.24 to -1.57] mm in the basal electrode). This difference, which was most prominent in the first third and latter third of the basal turn, decreased after the basal turn. CONCLUSIONS AND RELEVANCE: The RWI approach was associated with an increased likelihood of perimodiolar placement. Opting to use RWI over cochleostomy approaches in CI candidates may position electrodes closer to cochlear neural substrates and minimize current spread. These findings need to be interpreted in light of the increased potential for osseous spiral lamina trauma with reduced distances between the electrode array and modiolus. PMID- 27355199 TI - Nitrogen-Doped Carbon Embedded MoS2 Microspheres as Advanced Anodes for Lithium- and Sodium-Ion Batteries. AB - Rational design and synthesis of advanced anode materials are extremely important for high-performance lithium-ion and sodium-ion batteries. Herein, a simple one step hydrothermal method is developed for fabrication of N-C@MoS2 microspheres with the help of polyurethane as carbon and nitrogen sources. The MoS2 microspheres are composed of MoS2 nanoflakes, which are wrapped by an N-doped carbon layer. Owing to its unique structural features, the N-C@MoS2 microspheres exhibit greatly enhanced lithium- and sodium-storage performances including a high specific capacity, high rate capability, and excellent capacity retention. Additionally, the developed polyurethane-assisted hydrothermal method could be useful for the construction of many other high-capacity metal oxide/sulfide composite electrode materials for energy storage. PMID- 27355200 TI - Clean Donor Oxidation Enhances the H2 Evolution Activity of a Carbon Quantum Dot Molecular Catalyst Photosystem. AB - Carbon quantum dots (CQDs) are new-generation light absorbers for photocatalytic H2 evolution in aqueous solution, but the performance of CQD-molecular catalyst systems is currently limited by the decomposition of the molecular component. Clean oxidation of the electron donor by donor recycling prevents the formation of destructive radical species and non-innocent oxidation products. This approach allowed a CQD-molecular nickel bis(diphosphine) photocatalyst system to reach a benchmark lifetime of more than 5 days and a record turnover number of 1094+/-61 molH2 (molNi )(-1) for a defined synthetic molecular nickel catalyst in purely aqueous solution under AM1.5G solar irradiation. PMID- 27355201 TI - Sensing Enzymatic Activity by Exposure and Selection of DNA-Encoded Probes. AB - A sensing approach is applied to encode quantitative enzymatic activity information into DNA sequence populations. The method utilizes DNA-linked peptide substrates as activity probes. Signal detection involves chemical manipulation of a probe population downstream of sample exposure and application of purifying, selective pressure for enzyme products. Selection-induced changes in DNA abundance indicate sample activity. The detection of protein kinase, protease, and farnesyltransferase activities is demonstrated. The assays were employed to measure enzyme inhibition by small molecules and activity in cell lysates using parallel DNA sequencing or quantitative PCR. This strategy will allow the extensive infrastructure for genetic analysis to be applied to proteomic assays, which has a number of advantages in throughput, sensitivity, and sample multiplexing. PMID- 27355202 TI - Choosing Wavelet Methods, Filters, and Lengths for Functional Brain Network Construction. AB - Wavelet methods are widely used to decompose fMRI, EEG, or MEG signals into time series representing neurophysiological activity in fixed frequency bands. Using these time series, one can estimate frequency-band specific functional connectivity between sensors or regions of interest, and thereby construct functional brain networks that can be examined from a graph theoretic perspective. Despite their common use, however, practical guidelines for the choice of wavelet method, filter, and length have remained largely undelineated. Here, we explicitly explore the effects of wavelet method (MODWT vs. DWT), wavelet filter (Daubechies Extremal Phase, Daubechies Least Asymmetric, and Coiflet families), and wavelet length (2 to 24)-each essential parameters in wavelet-based methods-on the estimated values of graph metrics and in their sensitivity to alterations in psychiatric disease. We observe that the MODWT method produces less variable estimates than the DWT method. We also observe that the length of the wavelet filter chosen has a greater impact on the estimated values of graph metrics than the type of wavelet chosen. Furthermore, wavelet length impacts the sensitivity of the method to detect differences between health and disease and tunes classification accuracy. Collectively, our results suggest that the choice of wavelet method and length significantly alters the reliability and sensitivity of these methods in estimating values of metrics drawn from graph theory. They furthermore demonstrate the importance of reporting the choices utilized in neuroimaging studies and support the utility of exploring wavelet parameters to maximize classification accuracy in the development of biomarkers of psychiatric disease and neurological disorders. PMID- 27355204 TI - Lobular Breast Cancer and Abdominal Metastases: A Retrospective Review and Impact on Survival. AB - BACKGROUND: The predominant breast cancer subtypes, invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), have similar recurrence and survival rates but differing patterns of metastatic recurrence. METHODS: A retrospective review of breast cancers treated at an academic medical center from 1999 to 2012 was performed. Demographic, pathologic, treatment, and follow-up data were collected for 179 ILC and 358 IDC patients (1:2 stage-matched). The median follow up was 4.7 years. RESULTS: The baseline characteristics were similar in the two groups. ILC was more likely to be hormone-receptor-positive/HER2-negative and mammographically occult. The number of surgical resections, breast conservation rate, systemic treatment, and taxane use was similar between the groups. The overall recurrence rate was the same. ILC recurred more often in the abdominal cavity (24.3% in ILC vs. 4.1% in IDC, p = 0.001). The disease-free survival and overall survival were equal. On multivariate analysis, age, stage of disease, hormone receptor status, and systemic therapy were associated with survival, but histology was not. CONCLUSIONS: Compared to ductal breast cancers, lobular breast cancers recur more often in the abdominal cavity. Both ILC and IDC have comparable surgical and medical treatment outcomes and survival. Our data suggest that enhanced surveillance and imaging might be useful in ILC. PMID- 27355203 TI - Identification of a Disulfide Bridge in Sodium-Coupled Neutral Amino Acid Transporter 2(SNAT2) by Chemical Modification. AB - Sodium-coupled neutral amino acid transporter 2 (SNAT2) belongs to solute carrier 38 (SLC38) family of transporters, which is ubiquitously expressed in mammalian tissues and mediates transport of small, neutral amino acids, exemplified by alanine(Ala, A). Yet structural data on SNAT2, including the relevance of intrinsic cysteine residues on structure and function, is scarce, in spite of its essential roles in many tissues. To better define the potential of intrinsic cysteines to form disulfide bonds in SNAT2, mutagenesis experiments and thiol specific chemical modifications by N-ethylmaleimide (NEM) and methoxy polyethylene glycol maleimide (mPEG-Mal, MW 5000) were performed, with or without the reducing regent dithiothreitol (DTT) treatment. Seven single mutant transporters with various cysteine (Cys, C) to alanine (Ala, A) substitutions, and a C245,279A double mutant were introduced to SNAT2 with a hemagglutinin (HA) tag at the C-terminus. The results showed that the cells expressing C245A or C279A were labeled by one equivalent of mPEG-Mal in the presence of DTT, while wild-type or all the other single Cys to Ala mutants were modified by two equivalents of mPEG-Mal. Furthermore, the molecular weight of C245,279A was not changed in the presence or absence of DTT treatment. The results suggest a disulfide bond between Cys245 and Cys279 in SNAT2 which has no effect on cell surface trafficking, as well as transporter function. The proposed disulfide bond may be important to delineate proximity in the extracellular domain of SNAT2 and related proteins. PMID- 27355205 TI - Exogenous Magnesium Chloride Reduces the Activated Partial Thromboplastin Times of Lupus Anticoagulant-Positive Patients. AB - The activated partial thromboplastin time (APTT) assay is a basic hemostatic assay based on the time it takes for clots to form in plasma samples after the addition of calcium chloride. It is used to screen for various coagulation disorders. Several previous reports have suggested that magnesium (Mg) might contribute to coagulation reactions by binding to specific coagulation proteins. We investigated the effects of Mg on the APTT. In healthy controls, the APTT was significantly prolonged in proportion to the increase in the concentration of magnesium chloride in the range from 2.1 to 16.7 mmol/L. Among eight samples from patients with various disorders that exhibited prolonged APTT, two samples demonstrated shorter APTT when Mg was added, both of which were from patients that were positive for lupus anticoagulant. When we examined 206 clinical APTT samples, we found that Mg shortened the APTT of two samples. These two samples were also from lupus anticoagulant-positive patients (p-value: <0.003). Our findings regarding the unique effects of exogenous Mg on the APTT of lupus anticoagulant-positive patients might shed light on the role of Mg in APTT assays and lead to the development of a novel screening method for lupus anticoagulant. PMID- 27355206 TI - Editorial. PMID- 27355207 TI - Targeted Mutagenesis of the Hypophysiotropic Gnrh3 in Zebrafish (Danio rerio) Reveals No Effects on Reproductive Performance. AB - Gnrh is the major neuropeptide regulator of vertebrate reproduction, triggering a cascade of events in the pituitary-gonadal axis that result in reproductive competence. Previous research in mice and humans has demonstrated that Gnrh/GNRH null mutations result in hypogonadotropic hypogonadism and infertility. The goal of this study was to eliminate gnrh3 (the hypophysiotropic Gnrh form) function in zebrafish (Danio rerio) to determine how ontogeny and reproductive performance are affected, as well as factors downstream of Gnrh3 along the reproductive axis. Using the TALEN technology, we developed a gnrh3-/- zebrafish line that harbors a 62 bp deletion in the gnrh3 gene. Our gnrh3-/- zebrafish line represents the first targeted and heritable mutation of a Gnrh isoform in any organism. Using immunohistochemistry, we verified that gnrh3-/- fish do not possess Gnrh3 peptide in any regions of the brain. However, other than changes in mRNA levels of pituitary gonadotropin genes (fshb, lhb, and cga) during early development, which are corrected by adulthood, there were no changes in ontogeny and reproduction in gnrh3-/- fish. The gnrh3-/- zebrafish are fertile, displaying normal gametogenesis and reproductive performance in males and females. Together with our previous results that Gnrh3 cell ablation causes infertility, these results indicate that a compensatory mechanism is being activated, which is probably primed early on upon Gnrh3 neuron differentiation and possibly confined to Gnrh3 neurons. Potential compensation factors and sensitive windows of time for compensation during development and puberty should be explored. PMID- 27355208 TI - Appropriateness of Repeating Helicobacter pylori Culture and Susceptibility Testing Following Failure of Individualized Antibiotic Therapy. AB - BACKGROUND: Current guidelines recommend direct Helicobacter pylori culture and antibiotic susceptibility testing following 2 failed eradication attempts. If this process is followed and yet subsequent treatment is unsuccessful, it is unclear whether susceptibility testing should be repeated. This is the first study to examine the appropriateness of repeated H. pylori culture and susceptibility testing following failure of individualized treatment. METHODS: Between 2007 and 2014, consecutive patients who underwent at least 2 upper gastrointestinal endoscopies with H. pylori culture and susceptibility testing at our institution following several treatment failures were retrospectively identified. Antibiotic susceptibility was recorded and linked to demographic data. RESULTS: A total of 68 cultures from 34 patients were included (12 (35.3%) men, 41.4 +/- 16.6 years), and 20 (58.8%) cultures had a different antibiotic susceptibility profile on repeat testing (8 (23.5%) with new susceptibility and 13 (38.2%) with new resistance). Acquired resistance to clarithromycin, levofloxacin and metronidazole was observed in 9 (26.5%), 2 (5.9%) and 10 (29.4%) cultures, respectively. Subjects with resistance to <=1 antibiotic at baseline were more likely to develop resistance to at least 1 antibiotic on subsequent culture, compared to subjects with resistance to >=2 antibiotics at baseline (13 (100%) vs. 5 (23.8%), p < 0.01). CONCLUSION: Repeating H. pylori culture and susceptibility testing usually yields new antimicrobial susceptibility data. However, the clinical usefulness of this approach remains unclear. PMID- 27355209 TI - Yalongjiang River Has Had an Important Role in the Dispersal and Divergence of Rosa soulieana in the Hengduan Mountains of China. AB - The Hengduan Mountains are the core of the Sino-Himalayan Floristic Region. Rosa soulieana Crep. is an important wild rose species that is widely distributed in the Hengduan Mountains. To provide better future utilization of this wild rose, and also to add some possible proof of the effect of geomorphological and ecological characteristics of the Hengduan Mountains on the current spatial distribution and genetic diversity of local species, the genetic diversity and genetic structure of 556 individuals from 37 populations of R. soulieana were studied using fluorescent amplified fragment length polymorphisms (AFLPs). R. soulieana showed a moderately high level of genetic diversity and a high level of genetic differentiation at the species level. The total percentage of polymorphic loci, total heterozygosity (Ht), Shannon index (I), and heterozygosity value within populations (Hs) were 97.8%, 0.253, 0.339, and 0.139, respectively. More than half of the total genetic variation (54.0%) occurred within populations, and the overall gene differentiation coefficient (Gst) was 0.451. The genetic differentiation among populations was positively and significantly correlated with geographic distance. The neighbor-joining cluster and the Bayesian analysis divided all the populations and individuals into 3 groups, and did not support the morphology based intraspecific varieties. The results confirmed that the ancient R. soulieana of the third group survived in northwestern Yunnan and Yalongjiang valley and then moved upnorth along the valley. The spatial distribution of the other two groups was the result of allopatric divergence due to long period of adaptation to the different climatic conditions of its distribution at either side of the Yalongjiang River. PMID- 27355211 TI - Structural Insights into a Novel Class of Aspartate Aminotransferase from Corynebacterium glutamicum. AB - Aspartate aminotransferase from Corynebacterium glutamicum (CgAspAT) is a PLP dependent enzyme that catalyzes the production of L-aspartate and alpha ketoglutarate from L-glutamate and oxaloacetate in L-lysine biosynthesis. In order to understand the molecular mechanism of CgAspAT and compare it with those of other aspartate aminotransferases (AspATs) from the aminotransferase class I, we determined the crystal structure of CgAspAT. CgAspAT functions as a dimer, and the CgAspAT monomer consists of two domains, the core domain and the auxiliary domain. The PLP cofactor is found to be bound to CgAspAT and stabilized through unique residues. In our current structure, a citrate molecule is bound at the active site of one molecule and mimics binding of the glutamate substrate. The residues involved in binding of the PLP cofactor and the glutamate substrate were confirmed by site-directed mutagenesis. Interestingly, compared with other AspATs from aminotransferase subgroup Ia and Ib, CgAspAT exhibited unique binding sites for both cofactor and substrate; moreover, it was found to have unusual structural features in the auxiliary domain. Based on these structural differences, we propose that CgAspAT does not belong to either subgroup Ia or Ib, and can be categorized into a subgroup Ic. The phylogenetic tree and RMSD analysis also indicates that CgAspAT is located in an independent AspAT subgroup. PMID- 27355210 TI - Optimization of a Membrane Feeding Assay for Plasmodium vivax Infection in Anopheles albimanus. AB - INTRODUCTION: Individuals exposed to malaria infections for a long time develop immune responses capable of blocking Plasmodium transmission to mosquito vectors, potentially limiting parasite spreading in nature. Development of a malaria TB vaccine requires a better understanding of the mechanisms and main effectors responsible for transmission blocking (TB) responses. The lack of an in vitro culture system for Plasmodium vivax has been an important drawback for development of a standardized method to assess TB responses to this parasite. This study evaluated host, vector, and parasite factors that may influence Anopheles mosquito infection in order to develop an efficient and reliable assay to assess the TB immunity. METHODS/PRINCIPAL FINDINGS: A total of 94 P. vivax infected patients were enrolled as parasite donors or subjects of direct mosquito feeding in two malaria endemic regions of Colombia (Tierralta, and Buenaventura). Parasite infectiousness was assessed by membrane feeding assay or direct feeding assay using laboratory reared Anopheles mosquitoes. Infection was measured by qPCR and by microscopically examining mosquito midguts at day 7 for the presence of oocysts. Best infectivity was attained in four day old mosquitoes fed at a density of 100 mosquitos/cage. Membrane feeding assays produced statistically significant better infections than direct feeding assays in parasite donors; cytokine profiles showed increased IFN-gamma, TNF and IL-1 levels in non infectious individuals. Mosquito infections and parasite maturation were more reliably assessed by PCR compared to microscopy. CONCLUSIONS: We evaluated mosquito, parasite and host factors that may affect the outcome of parasite transmission as measured by artificial membrane feeding assays. Results have led us to conclude that: 1) optimal mosquito infectivity occurs with mosquitoes four days after emergence at a cage density of 100; 2) mosquito infectivity is best quantified by PCR as it may be underestimated by microscopy; 3) host cellular immune response did not appear to significantly affect mosquito infectivity; and 4) no statistically significant difference was observed in transmission between mosquitoes directly feeding on humans and artificial membrane feeding assays. PMID- 27355212 TI - Multiplex APLP System for High-Resolution Haplogrouping of Extremely Degraded East-Asian Mitochondrial DNAs. AB - Mitochondrial DNA (mtDNA) serves as a powerful tool for exploring matrilineal phylogeographic ancestry, as well as for analyzing highly degraded samples, because of its polymorphic nature and high copy numbers per cell. The recent advent of complete mitochondrial genome sequencing has led to improved techniques for phylogenetic analyses based on mtDNA, and many multiplex genotyping methods have been developed for the hierarchical analysis of phylogenetically important mutations. However, few high-resolution multiplex genotyping systems for analyzing East-Asian mtDNA can be applied to extremely degraded samples. Here, we present a multiplex system for analyzing mitochondrial single nucleotide polymorphisms (mtSNPs), which relies on a novel amplified product-length polymorphisms (APLP) method that uses inosine-flapped primers and is specifically designed for the detailed haplogrouping of extremely degraded East-Asian mtDNAs. We used fourteen 6-plex polymerase chain reactions (PCRs) and subsequent electrophoresis to examine 81 haplogroup-defining SNPs and 3 insertion/deletion sites, and we were able to securely assign the studied mtDNAs to relevant haplogroups. Our system requires only 1*10-13 g (100 fg) of crude DNA to obtain a full profile. Owing to its small amplicon size (<110 bp), this new APLP system was successfully applied to extremely degraded samples for which direct sequencing of hypervariable segments using mini-primer sets was unsuccessful, and proved to be more robust than conventional APLP analysis. Thus, our new APLP system is effective for retrieving reliable data from extremely degraded East Asian mtDNAs. PMID- 27355214 TI - Spatial modeling of cutaneous leishmaniasis in the Andean region of Colombia. AB - The objective of this research was to identify environmental risk factors for cutaneous leishmaniasis (CL) in Colombia and map high-risk municipalities. The study area was the Colombian Andean region, comprising 715 rural and urban municipalities. We used 10 years of CL surveillance: 2000-2009. We used spatial temporal analysis - conditional autoregressive Poisson random effects modelling - in a Bayesian framework to model the dependence of municipality-level incidence on land use, climate, elevation and population density. Bivariable spatial analysis identified rainforests, forests and secondary vegetation, temperature, and annual precipitation as positively associated with CL incidence. By contrast, livestock agroecosystems and temperature seasonality were negatively associated. Multivariable analysis identified land use - rainforests and agro-livestock - and climate - temperature, rainfall and temperature seasonality - as best predictors of CL. We conclude that climate and land use can be used to identify areas at high risk of CL and that this approach is potentially applicable elsewhere in Latin America. PMID- 27355213 TI - Predicting Response Trajectories during Cognitive-Behavioural Therapy for Panic Disorder: No Association with the BDNF Gene or Childhood Maltreatment. AB - BACKGROUND: Anxiety disorders are highly prevalent and result in low quality of life and a high social and economic cost. The efficacy of cognitive-behavioural therapy (CBT) for anxiety disorders is well established, but a substantial proportion of patients do not respond to this treatment. Understanding which genetic and environmental factors are responsible for this differential response to treatment is a key step towards "personalized medicine". Based on previous research, our objective was to test whether the BDNF Val66Met polymorphism and/or childhood maltreatment are associated with response trajectories during exposure based CBT for panic disorder (PD). METHOD: We used Growth Mixture Modeling to identify latent classes of change (response trajectories) in patients with PD (N = 97) who underwent group manualized exposure-based CBT. We conducted logistic regression to investigate the effect on these trajectories of the BDNF Val66Met polymorphism and two different types of childhood maltreatment, abuse and neglect. RESULTS: We identified two response trajectories ("high response" and "low response"), and found that they were not significantly associated with either the genetic (BDNF Val66Met polymorphism) or childhood trauma-related variables of interest, nor with an interaction between these variables. CONCLUSIONS: We found no evidence to support an effect of the BDNF gene or childhood trauma-related variables on CBT outcome in PD. Future studies in this field may benefit from looking at other genotypes or using different (e.g. whole genome) approaches. PMID- 27355216 TI - Dimercaptosuccinic acid scan challenges in childhood urinary tract infection, vesicoureteral reflux and renal scarring investigation and management. AB - Vesicoureteral reflux (VUR) is a precipitating factor in acute pyelonephritis (APN), and a risk factor for renal scar formation, even if VUR and APN occur independently. There is no scientific evidence on a specific diagnostic evaluation of children after a febrile urinary tract infection (UTI). Based on recent literature and our clinical experience, we reviewed the role of 99mTc dimercaptosuccinic acid (DMSA) renal scan in UTI/VUR imaging. We also reviewed the DMSA challenges and controversies in UTI/VUR management. A DMSA renal scan is the most reliable tool for the establishment of the diagnosis of APN during febrile UTIs acute phase. The "top-down" approach focuses on kidney involvement during UTI rather than on VUR existence, with a goal of diagnosing APN and/or renal dysplasia. Therefore, DMSA is performed before void cysteourethrography (VCUG). Late DMSA scanning should be performed to evaluate the presence of permanent renal scars. DMSA may be considered valuable in the follow-up of children with VUR, in order to detect new renal scarring after breakthrough or recurrent UTIs. An abnormal DMSA scan comprises a risk factor for VUR identification after UTI, for recurrent UTIs, renal damage/scarring, renal function deterioration, and a negative predictive risk factor for VUR improvement and/or spontaneous resolution. An individualized DMSA risk-based dynamic approach may assist physicians on VUR management decisions. DMSA could play an important role in selecting children with UTI/VUR who would benefit from close monitoring and/or early intervention. However, more data are needed for evidence-based guidelines. PMID- 27355215 TI - Conidial germination in Scedosporium apiospermum, S. aurantiacum, S. minutisporum and Lomentospora prolificans: influence of growth conditions and antifungal susceptibility profiles. AB - In the present study, we have investigated some growth conditions capable of inducing the conidial germination in Scedosporium apiospermum, S. aurantiacum, S. minutisporum and Lomentospora prolificans. Germination in Sabouraud medium (pH 7.0, 37oC, 5% CO2) showed to be a typically time-dependent event, reaching ~75% in S. minutisporum and > 90% in S. apiospermum, S. aurantiacum and L. prolificans after 4 h. Similar germination rate was observed when conidia were incubated under different media and pHs. Contrarily, temperature and CO2 tension modulated the germination. The isotropic conidial growth (swelling) and germ tube-like projection were evidenced by microscopy and cytometry. Morphometric parameters augmented in a time-dependent fashion, evidencing changes in size and granularity of fungal cells compared with dormant 0 h conidia. In parallel, a clear increase in the mitochondrial activity was measured during the transformation of conidia into-germinated conidia. Susceptibility profiles to itraconazole, fluconazole, voriconazole, amphotericin B and caspofungin varied regarding each morphotype and each fungal species. Overall, the minimal inhibitory concentrations for hyphae were higher than conidia and germinated conidia, except for caspofungin. Collectively, our study add new data about the conidia-into-hyphae transformation in Scedosporium and Lomentospora species, which is a relevant biological process of these molds directly connected to their antifungal resistance and pathogenicity mechanisms. PMID- 27355218 TI - Matrix metalloproteinase 9 and prostate cancer risk: a meta-analysis of 1059 participants. AB - INTRODUCTION: Numerous studies have evaluated the association between the matrix metalloproteinase 9 (MMP-9) and prostate cancer (PCa) risk. However, these studies have yielded conflicting results. EVIDENCE ACQUISITION: A comprehensive search was conducted through researching MEDLINE, PubMed, Web of Science, and EMBASE, and a total of 10 studies including 1059 cases were included on the basis of inclusion criteria. EVIDENCE SYNTHESIS: A meta-analysis was performed to obtain a summary of estimated odds ratios (ORs) and 95% confidence intervals (CIs) of MMP-9 for PCa, with attention to study quality and publication bias. MMP 9 by immunohistochemistry was significantly associated with increased diagnosis of PCa (OR=7.91; 95% CI: 5.27-11.89; P<0.00001). Subgroup-analysis showed that findings did not substantially change when only Caucasians or Asians (OR=5.87; 95% CI: 3.38-10.20; P<0.00001) or (OR=11.80; 95% CI: 6.60-21.08; P<0.00001) were considered. There was also no significant publication bias observed. CONCLUSIONS: Our findings provide further evidence that the expression of MMP-9 contribute to PCa risk. MMP-9 protein overexpression was found in prostate cancers, low expression in any of the normal tissues or in benign prostatic tissue. MMP-9 is potentially an important prostate tumor marker. PMID- 27355219 TI - Toll-like receptors are essential for the control of endogenous retrovirus expression in Idiopathic Nephrotic Syndrome. AB - BACKGROUND: Idiopathic nephrotic syndrome (INS) in children is a continuum of clinical disorders characterized by severe proteinuria, dyslipidemia, hypoalbuminemia, and hypercoagulability. It has been hypothesized that toll-like receptors (TLRs) in peripheral blood mononuclear cell might be involved in INS disease. Infections appear to be involved in the onset of INS. The aim of this study was to investigate the expression and function of TLRs in PBMC of INS patients and the relation with two human endogenous retrovirus (HERV), K and W expression. METHODS: The study enrolled 37 children at the exordium and without treatments of minimal-change disease (MCD), the most common single form of nephrotic syndrome (INS) and 20 healthy controls (HC). Relative quantification of target genes expression in patients compared with normal samples was performed with the DeltaDeltaCt method. RESULTS: HERV K and W were expressed in all samples analyzed but the level of expression was much lower in the INS that in HC P<0.0001 and P=0.0002 for HERV-K and -W, respectively. TLR2 was hyperexpressed in 10 vs. 17 (58.8%) of the INS, TLR3 in 3 vs. 17 (17.6%), TLR4 in 12 vs. 17 (70.6%) and TLR9 in 9 vs. 17 (52.9%) (Figure 2). The different expression were statistically significance in the case of TLR2, 3 and 4 (P=0.0183, 0.0218 and 0.0034, respectively) no for TLR9 (P=0.2010). Statistical analysis demonstrated a significance correlation between the low expression of HERV-K and HERV-W and high expression of TLRs. We obtain a statistically significance P<0.0001 considering all TLRs expression in comparison with HERV expression. CONCLUSIONS: We described a down regulation of pol gene of HERV-W and HERV-K mediated by TLRs. PMID- 27355220 TI - [The Offer of Medical-Diagnostic Self-Tests on German Language Websites: Results of a Systematic Internet Search]. AB - AIM OF THE STUDY: The aim of the current study was to provide an overview of medical-diagnostic self-tests which can be purchased without a medical prescription on German language websites. METHOD: From September 2014 to March 2015, a systematic internet research was conducted with the following search terms: self-test, self-diagnosis, home test, home diagnosis, quick test, rapid test. RESULTS: 513 different self-tests for the diagnostics of 52 diverse diseases or health risks were identified, including chronic diseases (e. g. diabetes, chronic disease of the kidneys, liver, and lungs), sexually transmitted diseases (e. g. HIV, chlamydia, gonorrhea), infectious diseases (e. g. tuberculosis, malaria, Helicobacter pylori), allergies (e. g. house dust, cats, histamine) and cancer as well as tests for the diagnostics of 12 different psychotropic substances. These were sold by 90 companies in Germany and by other foreign companies. CONCLUSION: The number of medical-diagnostic self-tests which can be bought without a medical prescription on the Internet has increased enormously in the last 10 years. Further studies are needed for the identification of the determinants of the use of self-tests as well as the impact of the application on the experience and behavior of the user. PMID- 27355221 TI - [Participation as Target of Social Medicine and Nursing Care: - Legal Definition of Long-Term Care Dependency - Strategies to Prevent Long-Term Care Dependency]. AB - Objective: By the "Second Bill to Strengthen Long-Term Care", a new concept of long-term care dependency will be introduced, valid from 2017. Long-term care dependency according to Social Code XI will be defined covering more aspects than today. Therefore, the working group "Nursing Care" of the division "Social Medicine in Practice and Rehabilitation" in the German Society for Social Medicine and Prevention presents their results after working on the social medicine perspective of the definition and prevention of long-term care dependency. Methods: Both the definition and strategies to prevent long-term care dependency are systematically taken into consideration from the point of view of social medicine on the basis of the International Classification of Functioning, Disability and Health (ICF), as long-term care dependency means a defined condition of disability. Results: Both the current and the new concept of long term care dependency focus activity limitations. The perspective of social medicine considers the interactions of health condition, its effects on daily activities and personal as well as environmental factors. From this point of view approaches for social benefits concerning prevention and rehabilitation can be identified systematically so as to work against the development and progression of long-term care dependency. The reference to the ICF can facilitate the communication between different professions. The new "graduation" of long-term care dependency would allow an international "translation" referring to the ICF. Conclusion: Experts from the field of social medicine as well as those of nursing care, care-givers and nursing researchers have in common the objective that persons in need of nursing care can participate in as many aspects of life of importance to them in an autonomous and self-determined way. The point of view of social medicine on long-term care dependency is fundamental for all occupational groups that are involved and for their successful cooperation. PMID- 27355223 TI - A novel approach to neutron scattering instrumentation for probing multiscale dynamics in soft and biological matter. AB - We present a concept and ray-tracing simulation of a mechanical device that will enable inelastic neutron scattering measurements where the data at energy transfers from a few MUeV to several hundred meV can be collected in a single, gapless spectrum. Besides covering 5 orders of magnitude on the energy (time) scale, the device provides data over 2 orders of magnitude on the scattering momentum (length) scale in a single measurement. Such capabilities are geared primarily toward soft and biological matter, where the broad dynamical features of relaxation origin largely overlap with vibration features, thus necessitating gapless spectral coverage over several orders of magnitude in time and space. Furthermore, neutron scattering experiments with such a device are performed with a fixed neutron final energy, which enables measurements, with neutron energy loss in the sample, at arbitrarily low temperatures over the same broad spectral range. This capability is also invaluable in biological and soft matter research, as the variable temperature dependence of different relaxation components allows their separation in the scattering spectra as a function of temperature. PMID- 27355222 TI - Sepsis: the LightCycler SeptiFast Test MGRADE(r), SepsiTestTM and IRIDICA BAC BSI assay for rapidly identifying bloodstream bacteria and fungi - a systematic review and economic evaluation. AB - BACKGROUND: Sepsis can lead to multiple organ failure and death. Timely and appropriate treatment can reduce in-hospital mortality and morbidity. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of three tests [LightCycler SeptiFast Test MGRADE((r)) (Roche Diagnostics, Risch-Rotkreuz, Switzerland); SepsiTest(TM) (Molzym Molecular Diagnostics, Bremen, Germany); and the IRIDICA BAC BSI assay (Abbott Diagnostics, Lake Forest, IL, USA)] for the rapid identification of bloodstream bacteria and fungi in patients with suspected sepsis compared with standard practice (blood culture with or without matrix absorbed laser desorption/ionisation time-of-flight mass spectrometry). DATA SOURCES: Thirteen electronic databases (including MEDLINE, EMBASE and The Cochrane Library) were searched from January 2006 to May 2015 and supplemented by hand-searching relevant articles. REVIEW METHODS: A systematic review and meta analysis of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. A decision tree was used to estimate the costs and quality-adjusted life-years (QALYs) associated with each test; all other parameters were estimated from published sources. The model was populated with evidence from the systematic review or individual studies, if this was considered more appropriate (base case 1). In a secondary analysis, estimates (based on experience and opinion) from seven clinicians regarding the benefits of earlier test results were sought (base case 2). A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Scenario analyses were used to assess uncertainty. RESULTS: For the review of diagnostic test accuracy, 62 studies of varying methodological quality were included. A meta-analysis of 54 studies comparing SeptiFast with blood culture found that SeptiFast had an estimated summary specificity of 0.86 [95% credible interval (CrI) 0.84 to 0.89] and sensitivity of 0.65 (95% CrI 0.60 to 0.71). Four studies comparing SepsiTest with blood culture found that SepsiTest had an estimated summary specificity of 0.86 (95% CrI 0.78 to 0.92) and sensitivity of 0.48 (95% CrI 0.21 to 0.74), and four studies comparing IRIDICA with blood culture found that IRIDICA had an estimated summary specificity of 0.84 (95% CrI 0.71 to 0.92) and sensitivity of 0.81 (95% CrI 0.69 to 0.90). Owing to the deficiencies in study quality for all interventions, diagnostic accuracy data should be treated with caution. No randomised clinical trial evidence was identified that indicated that any of the tests significantly improved key patient outcomes, such as mortality or duration in an intensive care unit or hospital. Base case 1 estimated that none of the three tests provided a benefit to patients compared with standard practice and thus all tests were dominated. In contrast, in base case 2 it was estimated that all cost per QALY-gained values were below L20,000; the IRIDICA BAC BSI assay had the highest estimated incremental net benefit, but results from base case 2 should be treated with caution as these are not evidence based. LIMITATIONS: Robust data to accurately assess the clinical effectiveness and cost effectiveness of the interventions are currently unavailable. CONCLUSIONS: The clinical effectiveness and cost-effectiveness of the interventions cannot be reliably determined with the current evidence base. Appropriate studies, which allow information from the tests to be implemented in clinical practice, are required. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015016724. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 27355224 TI - Access to diabetes drugs in New Zealand is inadequate. PMID- 27355225 TI - The management of Graves' disease in New Zealand 2014. AB - BACKGROUND: Treatment options for Graves' disease (GD), namely anti-thyroid drugs (ATD), surgery or radioiodine (RAI), have not changed over the past two decades. There is no 'gold-standard' treatment for GD. AIMS: To assess whether the management of GD in New Zealand has changed since the previous 1991 New Zealand survey and compare current management with that of contemporary international studies. METHODS: We conducted an online survey of New Zealand physicians currently practising internal medicine, diabetes and/or endocrinology, using the cases and questions from the original European and 1991 New Zealand studies. RESULTS: The first-line use of RAI was 5.5%, compared to 41% in the 1991 New Zealand survey. This corresponded to an increase in ATD use, while the rates of surgery as a first-line treatment have remained static over time. New Zealand physicians use technetium scanning for diagnosis, whereas ultrasound and radioiodine uptake were the most commonly selected investigations by European and North American physicians, respectively. The pattern of ATD use in pregnancy was similar to international practice. CONCLUSION: Treatment of GD in New Zealand has shifted away from the use of RAI as first line treatment. There are significant differences in the investigation and treatment of Grave's disease between New Zealand, Europe and North America. PMID- 27355226 TI - Geography matters: the prevalence of diabetes in the Auckland Region by age, gender and ethnicity. AB - AIM: To determine whether the prevalence of diagnosed diabetes in the greater Auckland Region varies by General Electoral District (GED). METHODS: Using encrypted National Health Identifiers and record linkage of routine health datasets, we identified a regional cohort of people with diagnosed diabetes in 2011 from inpatient records and medication dispensing. The geographical unit of a person's residence (meshblock) was used to determine the GED of residence. We calculated prevalence estimates and 95% confidence intervals and used binary logistic regression to map geographical variations in diabetes. RESULTS: An estimated 63,014 people had diagnosed diabetes in Auckland in 2011, a prevalence of 8.5% of the adult population >=30 years of age. We found significant variation in diabetes prevalence by age, gender, ethnicity and GED. There was a more than five-fold difference in the unadjusted prevalence of diabetes by GED, ranging from 3.2% (3.1 to 3.4%) in the North Shore to 17.3% (16.8 to 17.7%) in Mangere. Such variations remained after binary logistic regression adjusting for socio demographic variables. Compared to New Zealand Europeans, Indian people had the highest odds of having diabetes at 3.85 (3.73 to 3.97), while the odds of people living in the most deprived areas having diabetes was nearly twice that of those living in least deprived areas (OR 1.93, [1.87 to 1.99]). Geographic variations in diabetes remained after adjusting for socio-demographic circumstances: people living in GEDs in south-west Auckland were at least 60% more likely than people living in the North Shore GED to have diabetes. CONCLUSIONS: There is significant variation in the prevalence of diabetes by GED in Auckland that persists across strata of age group, gender and ethnicity, and persists after controlling for these same variables. These inequities should prompt action by politicians, policymakers, funders, health providers and communities for interventions aimed at reducing such inequities. Geography and its implications on access to and availability of health resources appears to be a key driver of inequity in diabetes rates, supporting an argument for interventions based on geography, especially a public health rather than an individual risk approach. PMID- 27355227 TI - Trampoline-associated injuries are more common in children in spring. AB - AIMS: Trampoline use is a popular pastime amongst children in New Zealand, and has many advantages for child development. However, recent reports claim that trampoline-associated injuries are still highly prevalent. In order to help prevent these injuries in the future, this study aims to provide more up-to-date epidemiological information in children, with emphasis on the time of year that injuries most commonly occur. METHODS: A retrospective review was carried out utilising a prospective maintained trauma database. The database was searched electronically for injuries involving trampolines in children aged 0-15 years. Patient demographics and information regarding month of injury, injury type and management were extracted. RESULTS: There were 344 admissions to hospital for trampoline-related injuries between June 2000 and January 2015. Injuries were uncommon in winter, but rose in spring and summer. Fracture of the radius and/or ulna was the most common injury (34.0%), followed by humeral fracture (32.0%). CONCLUSION: The peak incidence of trampoline-related injuries occurred around the beginning of spring daylight savings time each year. This could therefore prove an opportune time to remind children and parents about trampoline safety at the same time as daylight savings reminders. PMID- 27355228 TI - Use of full strength fluoride toothpaste among preschoolers in New Zealand, and factors determining toothpaste choice. AB - AIM: International researchers have highlighted an inconsistent knowledge-base for parents and caregivers regarding the use of toothpaste among preschoolers. The New Zealand Government has published recommendations on the use of toothpaste in this age group. This study aimed to explore parents and caregivers' knowledge about toothpaste, with the aim of improving health literacy and overall oral health of New Zealand preschoolers. METHOD: The study was conducted via an online sample of parents and caregivers of preschoolers (n=1,056). RESULTS: Only 19% of the preschoolers in the sample used full-strength fluoride toothpaste. Preschoolers were significantly more likely to use full-strength toothpaste if they were not the first child in the family (OR=1.77, 1.28-2.47) or have previously visited a dental professional (OR=1.84, 1.18-2.85). In addition, parents and caregivers made decisions around purchasing of toothpaste based on the level of trust they had in the brand (59%) and also matching age-specific toothpaste to their child (49%). CONCLUSION: The findings of this research highlight the need for timely advice for parents and caregivers on toothpaste choices for preschool children. The New Zealand Government has published recommendations on the use of full-strength fluoride toothpaste for all ages, including pre-schoolers. PMID- 27355230 TI - Screening, prevalence and ethnic variation of diabetes mellitus in people with acute stroke and transient ischaemic attack: a cross-sectional study in Northland, New Zealand. AB - AIM: To assess our prevalence and screening rate for diabetes and pre-diabetes in people presenting with acute stroke and transient ischaemic attack (TIA) in Northland, New Zealand, as well as identifying discrepancies between Māori and non-Māori, rates of atrial fibrillation (AF) and effect of metformin on stroke. METHOD: Data was collected retrospectively on people diagnosed with stroke or TIA in Northland, between 1 January 2014 and 31 December 2014. RESULTS: 345 people presented with acute stroke/TIA. 49.5% had dysglycaemia: 24.3% diabetes, 25.2% pre-diabetes. An HbA1c was performed on 70.4%. Māori had more diabetes (41.6%) than non-Māori (19.4%), with an HbA1c 12 mmol/mol (3.2%) higher, and were 12 years younger on average. There was no difference in AF prevalence between people with and without diabetes, and in the proportion of severe stroke (total anterior circulation infarction) between people with diabetes on metformin and those not. CONCLUSIONS: The prevalence of dysglycaemia in acute stroke/TIA in Northland is high. The goal of universal HbA1c screening in stroke is not being met. Māori have stroke younger, and a higher prevalence of diabetes may partially explain this. No association between diabetes and AF was found, nor evidence that metformin may be protective against larger strokes. PMID- 27355229 TI - Sleep of Māori and non-Māori of Advanced Age. AB - AIM: To estimate prevalence and identify predictors and outcomes of reporting sleep problems in Māori and non-Māori of advanced age. METHOD: Participants were 251 Māori, and 398 non-Māori adults (79-90 years) from Te Puāwaitanga o Ngā Tapuwae Kia Ora Tonu. Life and Living in Advanced Age: A Cohort Study in New Zealand. Multiple logistic regression identified predictors of reporting a current sleep problem and investigated relationships between current sleep problems and physical and mental health. RESULTS: 26.3% of Māori and 31.7% of non-Māori reported a current sleep problem. Reporting a current sleep problem was associated with ethnicity (non Māori, adjusted OR=0.52, 95% CI=0.30-0.90), and reporting a past sleep problem (adjusted OR=2.67, 95% CI=1.25-5.72). Sleep problems were related to poorer physical and mental health, and falling. CONCLUSION: Sleep problems are commonly reported and associated with poorer health. Early recognition and management of sleep problems could improve physical and mental health. PMID- 27355231 TI - Sublingual vitamin B12 compared to intramuscular injection in patients with type 2 diabetes treated with metformin: a randomised trial. AB - MAIM: To compare a single 1mg intramuscular hydroxocobalamin injection with a 3 month course of 1mg/day sublingual methylcobalamin supplements on serum vitamin B12 concentrations in participants withtype 2 diabetes treated with metformin. METHOD: Participants on metformin treatment with vitamin B12 concentrations below 220pmol/L were recruited through hospital diabetes clinics and primary care practices. They were randomised to receive either the injection or sublingual treatment. The primary outcome was serum vitamin B12 level after 3 months adjusted for baseline assessed by analysis of covariance (ANCOVA). The trial was registered on the Australia New Zealand Clinical Trial registry (ACTRN12612001108808). RESULTS: A total of 34 participants were randomised; 19 to the tablet, and 15 to the injection. The mean (SD) age, duration of diabetes, and duration of metformin use were, 64.2 (7.3) years, 13.7 (6.4) years, and 11.6 (5.0) years, respectively. After 3 months, the mean (SD) vitamin B12 was 372.1 (103.3) pmol/L in the tablet group (n=19) compared to 251.7 (106.8) pmol/L in the injection group (n=15), ANCOVA estimated difference -119.4 (95% CI -191.2 to 47.6), p=0.002. After 6 months, the mean (SD) serum B12 was 258.8 (58.7) pmol/L in the tablet group (n=17) and 241.9 (40.1) pmol/L in the injection group (n=15); ANCOVA estimated difference -15.2 (95% CI -50.3 to 19.8), p=0.38. Higher metformin dose was associated with lower serum B12 at 3 months, but not at baseline or 6 months. CONCLUSION: Decreased serum vitamin B12 level in patients with type 2 diabetes who are treated with metformin can be corrected through treatment with either hydroxocobalamin injections or methylcobalamin sublingual supplements. PMID- 27355232 TI - The case for a national service for primary immune deficiency disorders in New Zealand. AB - Primary immune deficiency disorders (PIDs) are rare conditions for which effective treatment is available. It is critical these patients are identified at an early stage to prevent unnecessary morbidity and mortality. Treatment of these disorders is expensive and expert evaluation and ongoing management by a clinical immunologist is essential. Until recently there has been a major shortage of clinical immunologists in New Zealand. While the numbers of trained immunologists have increased in recent years, most are located in Auckland. The majority of symptomatic PID patients require life-long immunoglobulin replacement. Currently there is a shortage of subcutaneous and intravenous immunoglobulin (SCIG/IVIG) in New Zealand. A recent audit by the New Zealand Blood Service (NZBS) showed that compliance with indications for SCIG/IVIG treatment was poor in District Health Boards (DHBs) without an immunology service. The NZBS audit has shown that approximately 20% of annual prescriptions for SCIG/IVIG, costing $6M, do not comply with UK or Australian guidelines. Inappropriate use may have contributed to the present shortage of SCIG/IVIG necessitating importation of the product. This is likely to have resulted in a major unnecessary financial burden to each DHB. Here we present the case for a national service responsible for the tertiary care of PID patients and oversight for immunoglobulin use for primary and non haematological secondary immunodeficiencies. We propose that other PIDs, including hereditary angioedema, are integrated into a national PID service. Ancillary services, including the customised genetic testing service, and research are also an essential component of an integrated national PID service and are described in this review. As we show here, a hub-and-spoke model for a national service for PIDs would result in major cost savings, as well as improved patient care. It would also allow seamless transition from paediatric to adult services. PMID- 27355233 TI - Unprovoked DVT, the clot thickens. PMID- 27355234 TI - Leukoencephalopathy in an HIV Patient. PMID- 27355235 TI - Convenient Preparation and Detailed Analysis of a Series of NHC-Stabilized Phosphorus(I) Dyes and Their Derivatives. AB - A safe, convenient, and P-atom-efficient synthesis of N-heterocyclic-carbene- (NHC-) stabilized phosphorus(I) bromide salts is reported that involves P(+) transfer from an easily prepared triphosphenium precursor. The resulting family of phosphamethine cyanine dyes featuring N,N'-dialkyl-substituted 4,5 dimethylimidazole-2-ylidenes ((R)NHC(Me)) and benzimidazole-2-ylidenes ((R)NHC(B)) (R = Me, Et, iPr) have been fully characterized. We found that increasing N-alkyl group size causes increased twisting of the carbene fragments from the C-P-C plane, which decreases the magnitude of hyperconjugation between the pi-type lone pair on phosphorus and the carbene fragments. This decrease is manifested as changes in the (31)P NMR chemical shifts, magnitudes of the P-C coupling constants, and electronic spectra of the cations. The reactivities of these ions toward various oxidants are reported: Oxidation by sulfur generates dithiophosphinium salts, protonation or methylation gives dicationic phosphines, and coordination to 1 or 2 equiv of gold(I) chloride results in mono or bimetallic complexes, respectively. PMID- 27355236 TI - Individual Human Brain Areas Can Be Identified from Their Characteristic Spectral Activation Fingerprints. AB - The human brain can be parcellated into diverse anatomical areas. We investigated whether rhythmic brain activity in these areas is characteristic and can be used for automatic classification. To this end, resting-state MEG data of 22 healthy adults was analysed. Power spectra of 1-s long data segments for atlas-defined brain areas were clustered into spectral profiles ("fingerprints"), using k-means and Gaussian mixture (GM) modelling. We demonstrate that individual areas can be identified from these spectral profiles with high accuracy. Our results suggest that each brain area engages in different spectral modes that are characteristic for individual areas. Clustering of brain areas according to similarity of spectral profiles reveals well-known brain networks. Furthermore, we demonstrate task-specific modulations of auditory spectral profiles during auditory processing. These findings have important implications for the classification of regional spectral activity and allow for novel approaches in neuroimaging and neurostimulation in health and disease. PMID- 27355237 TI - Prescription Opioid Craving: Relationship With Pain and Substance Use-Related Characteristics. AB - BACKGROUND: Craving is associated with prescription opioid use in opioid-addicted pain patients. OBJECTIVES: This study evaluated the relationship between craving for prescription opioids and selected pain and substance use characteristics. METHOD: In this cross-sectional study, patients (N = 106) being treated for opioid dependence were recruited from one of three sites from December 2012 to April 2013. Participants completed the multi-dimensional Desire for Drugs Questionnaire to assess craving, and other questionnaires to assess pain, substance use, and demographic characteristics. Data were analyzed using Pearson product-by-moment correlations, ANOVAs, and multiple linear regressions. RESULTS: At the bivariate level, desire-and-intention to use prescription opioids and craving for relief from negative states were positively associated with both pain severity and interference. Linear regression analyses revealed significant positive associations between Desire-and-Intention subscale scores and obsessive thoughts and compulsive behaviors associated with prescription opioids and pain severity. Negative Reinforcement subscales scores were positively associated with obsessive thoughts and compulsive behaviors associated with prescription opioids and the outcome expectancies of pain reduction, but not pain severity. CONCLUSIONS/IMPORTANCE: This study extended previous research assessing the link between pain and craving by demonstrating that desire-and-intention, but not craving for the negative reinforcing effects are associated with pain severity after considering various substance use characteristics. Additional research is needed to clarify the relationship between pain and aspects of craving while also considering pain-specific covariates. This study highlights that the multi dimensionality of craving is an important aspect to consider when clinicians and researchers evaluate the relationship between pain and craving. PMID- 27355238 TI - Plasmonic Heating in Au Nanowires at Low Temperatures: The Role of Thermal Boundary Resistance. AB - Inelastic electron tunneling and surface-enhanced optical spectroscopies at the molecular scale require cryogenic local temperatures even under illumination conditions that are challenging to achieve with plasmonically resonant metallic nanostructures. We report a detailed study of the laser heating of plasmonically active nanowires at substrate temperatures from 5 to 60 K. The increase of the local temperature of the nanowire is quantified by a bolometric approach and could be as large as 100 K for a substrate temperature of 5 K and typical values of laser intensity. We also demonstrate that a ~3-fold reduction of the local temperature increase is possible by switching to a sapphire or quartz substrate. Finite element modeling of the heat dissipation reveals that the local temperature increase of the nanowire at temperatures below ~50 K is determined largely by the thermal boundary resistance of the metal-substrate interface. The model reproduces the striking experimental trend that in this regime the temperature of the nanowire varies nonlinearly with the incident optical power. The thermal boundary resistance is demonstrated to be a major constraint on reaching low temperatures necessary to perform simultaneous inelastic electron tunneling and surface-enhanced Raman spectroscopies. PMID- 27355240 TI - Synthesis of 1,3-Dienes via a Sequential Suzuki-Miyaura Coupling/Palladium Mediated Allene Isomerization Sequence. AB - We report a facile method for the synthesis of 1,3-dienes by a sequential process consisting of a palladium-catalyzed, base-free, Suzuki-Miyaura coupling/isomerization sequence. This sequence couples boronic acids with propargyl alcohols, generating the requisite allene in situ, followed by conversion of the unactivated allene to its 1,3-diene via a hydro palladation/dehydro-palladation process. This process is general for a range of boronic acids, including boronic acids with electron-donating and -withdrawing groups, as well as heteroarylboronic acids. Key to this process is the boric acid byproduct of the base-free Suzuki-Miyauru coupling, which generates the required palladium-hydrido complex [H-Pd(II)-OB(OH)2] required for the isomerization. PMID- 27355239 TI - Suppressing transthyretin production in mice, monkeys and humans using 2nd Generation antisense oligonucleotides. AB - Transthyretin amyloidosis (ATTR amyloidosis) is a rare disease that results from the deposition of misfolded transthyretin (TTR) protein from the plasma into tissues as amyloid fibrils, leading to polyneuropathy and cardiomyopathy. IONIS TTRRx (ISIS 420915) is a 2nd-Generation 2'-O-(2-methoxyethyl) modified "2'-MOE" antisense oligonucleotide (ASO) that targets the TTR RNA transcript and reduces the levels of the TTR transcript through an RNaseH1 mechanism of action, leading to reductions in both mutant and wild-type TTR protein. The activity of IONIS TTRRx to decrease TTR protein levels was studied in transgenic mice bearing the Ile84Ser human TTR mutant, in cynomolgus monkeys and in healthy human volunteers. Robust (>80%) reductions of plasma TTR protein were obtained in all three species treated with IONIS-TTRRx, which in mice and monkeys was associated with substantial reductions in hepatic TTR RNA levels. These effects were dose dependent and lasted for weeks post-dosing. In a Phase 1 healthy volunteer study, treatment with IONIS-TTRRx for four weeks was well tolerated without any remarkable safety issues. TTR protein reductions up to 96% in plasma were observed. These nonclinical and clinical results support the ongoing Phase 3 development of IONIS-TTRRx in patients with ATTR amyloidosis. PMID- 27355241 TI - Effects of strain on the electronic structure and magnetic properties in SrMn0.5Fe0.5O3. AB - The electronic structure and magnetic properties of SrMn0.5Fe0.5O3 powder and films grown on (1 0 0)-SrTiO3 (STO) and (1 0 0)-LaAlO3 (LAO) substrates by pulsed laser deposition (PLD) were investigated by temperature dependent magnetization and soft x-ray absorption. The results exhibit characteristics of 3d (5) Fe(3+), [Formula: see text], and 3d (3) + 3d (4) [Formula: see text] Mn(4+) at room temperature in all samples. However, the features of 3d (5) Fe(3+) and 3d (3) Mn(4+) increased significantly for SMFO/LAO at 35 K, which also displayed substantial competition between antiferromagnetic and ferromagnetic order well above the Neel temperature of SrFeO3 (T N ~ 134 K). We attributed this to being caused by charge disproportionation resulting from ligand-hole localization, which is more favorable to take place when the sample is under compressive strain. PMID- 27355242 TI - Insulin-Like Peptide 5 Interacts with Sex Hormones and Metabolic Parameters in a Gender and Adiposity Dependent Manner in Humans. AB - Insulin-like peptide 5 (INSL5) is a gut hormone produced by L-cells in the colorectal epithelium and may play a role in the regulation of metabolic processes. The biological role of INSL5 is poorly investigated and nothing is known about the role of this hormone in obese and lean humans. Two cohorts were analyzed in the study. In the first cohort (n=76) the relationship between serum levels of INSL5 and different metabolic and hormonal parameters in obese and lean men and women were investigated. In the second cohort 14 male subjects underwent bariatric surgery. Circulating levels of INSL5 were then measured before and after interventions.We report for the first time that circulating INSL5 interacts with multiple metabolic and hormonal variables in lean and obese men and women and is affected by bariatric surgery. Serum levels of INSL5 negatively correlated with testosterone and blood lipids but positively with cortisol in obese men. In contrast to males, obese women had a strong negative correlation of plasma levels of INSL5 with C-reactive protein (CRP). We observed that adipose tissue loss after bariatric surgery significantly reduced serum levels of INSL5 in obese men with and without Type 2 Diabetes Mellitus (T2DM) that was associated with the restoration of circulating levels of testosterone. All together, our data demonstrated that INSL5 may interact with some metabolic parameters in obese humans and this process is dependent of gender and obesity state. PMID- 27355243 TI - The effects of the CLIMB(r) program on psychobehavioral functioning and emotion regulation in children with a parent or caregiver with cancer: A pilot study. AB - This study evaluated the psychobehavioral benefits of the Children's Lives Include Moments of Bravery (CLIMB(r)) intervention in 45 children (aged 6-11) with a parent/caregiver with cancer. Parent/caregiver reports of psychobehavioral functioning indicated signi-ficant decreases in children's emotional symptoms and marginally significant reductions in conduct problems. Child reports of emotion regulation indicated significant increases in emotion awareness, significant decreases in emotion suppression, and nonsignificant increases in emotion-focused coping and dysregulated expression. Parents/caregivers and children reported high satisfaction with CLIMB(r). Results suggest CLIMB(r) is a promising intervention for improving psychobehavioral functioning and emotion regulation in children with a parent/caregiver with cancer. PMID- 27355244 TI - LOW SERUM BRAIN-DERIVED NEUROTROPHIC FACTOR BUT NOT BRAIN-DERIVED NEUROTROPHIC FACTOR GENE VAL66MET POLYMORPHISM IS ASSOCIATED WITH DIABETIC RETINOPATHY IN CHINESE TYPE 2 DIABETIC PATIENTS. AB - BACKGROUND/PURPOSE: The aim of our research was to investigate the potential role of brain-derived neurotrophic factor (BDNF) in diabetic retinopathy (DR). Measurement of serum circulating levels of BDNF and analysis of polymorphism of BDNF gene (Val66Met) were applied and compared with diabetic patients without DR. METHODS: From February 2014 and March 2015, all eligible patients with Type 2 diabetic mellitus at our hospital were consecutively recruited (N = 404). Their serum BDNF levels were detected by enzyme-linked immunosorbent assay. BDNF val66met polymorphism genotyping was conducted according to the laboratory's standard protocol. At baseline, demographic and clinical data were taken. The relationship of BDNF with DR was investigated with the use of logistic regression models. Receiver operating characteristic curves were used to test the overall accuracy of BDNF and other markers. RESULTS: Diabetic patients with DR and vision threatening DR had significantly lower BDNF levels on admission (P < 0.0001 both). The BDNF genotyping results showed that there was no difference between the diabetic patients with DR and those without DR. Multivariate logistic regression analysis adjusted for common risk factors showed that serum BDNF levels were independent risk factors for DR (odds ratio = 0.86; 95% confidence interval [CI]: 0.80-0.92; P < 0.0001) and vision-threatening DR (odds ratio = 0.79; 95% CI: 0.75-0.85; P < 0.0001). Brain-derived neurotrophic factor improved the area under the receiver operating characteristic curve of the diabetes duration for DR from 0.69 (95% CI: 0.60-0.76) to 0.85 (95% CI: 0.79-0.90; P < 0.01) and for vision-threatening DR from 0.77 (95% CI: 0.67-0.87) to 0.86 (95% CI: 0.80-0.92; P < 0.01). CONCLUSION: The present study demonstrated that, rather than Val66Met polymorphism, decreased serum levels of BDNF were associated with DR and vision-threatening DR in Chinese Type 2 diabetic patients, suggesting a possible role of BDNF in the pathogenesis of DR complications. PMID- 27355258 TI - Survival of ovarian cancer patients in Denmark: Results from the Danish gynaecological cancer group (DGCG) database, 1995-2012. AB - BACKGROUND: Ovarian cancer has a high mortality rate, especially in Denmark where mortality rates have been reported higher than in adjacent countries with similar demographics. This study therefore examined recent survival and mortality among Danish ovarian cancer patients over an 18-year study period. METHODS: This nationwide registry-based observational study used data from the Danish Gynecology Cancer Database, Danish Pathology Registry, and Danish National Patient Registry. All patients with ovarian cancer diagnosed between 1995 and 2012 were included in the study. The data sources were linked via the patients' personal identification number and the analyses included data on cancer stage, age, survival, surgery status and comorbidity. The computed outcome measures were age-adjusted mortality rates and age-adjusted overall and relative survival rates for one and five years. RESULTS: We identified 9972 patients diagnosed with ovarian cancer in the period 1995-2012. The absolute one-year mortality rate decreased from 42.8 (CI 40.3-45.6) in 1995-1999 to 28.3 (CI 25.9-30.9) in 2010 2012, and the five-year mortality rate decreased from 28.2 (CI 27.0-29.5) in 1995 1999 to 23.9 (CI 22.9-25.0) in 2005-2009. After stratification by age, comorbidity and cancer stage, the decrease in one-year mortality was most substantial in the 65-74 year old age group 41.1 (CI 38.8-43.5) to 26.5 (CI 24.4 28.7) and for stage III 39.1 (CI 35.1-43.6) to 22.9 (CI 19.9-26.5) and stage IV 91.3 (CI 80.8-103.2) to 41.9 (CI 35.5-49.5). For overall survival, we showed an increase in one-year survival from 68% (CI 66-69%) in 1995-1999 to 76% (CI 74 78%) in 2010-2012 and an increase in five-year survival from 33% (CI 32-35%) in 1995-1999 to 36% (CI 34-38%) in 2005-2009. Relative survival showed similar increases through the period. CONCLUSIONS: Ovarian cancer survival in Denmark has improved substantially from 1995 to 2012, bringing Denmark closer to the standards set by adjacent countries. PMID- 27355245 TI - Mortality among military participants at the 1957 PLUMBBOB nuclear weapons test series and from leukemia among participants at the SMOKY test. AB - Health effects following low doses of ionizing radiation are uncertain. Military veterans at the Nevada test site (NTS) during the SMOKY atmospheric nuclear weapons test in 1957 were reported to be at increased risk for leukemia in 1979, but this increase was not evaluated with respect to radiation dose. The SMOKY test was one of 30 tests in 1957 within the PLUMBBOB test series. These early studies led to public laws where atomic veterans could qualify for compensation for presumptive radiogenic diseases. A retrospective cohort study was conducted of 12219 veterans at the PLUMBBOB test series, including 3020 at the SMOKY nuclear test. Mortality follow-up was through 2010 and observed causes of death were compared with expected causes based on general population rates. Radiation dose to red bone marrow was based on individual dose reconstructions, and Cox proportional hazards models were used to evaluate dose response for all leukemias other than chronic lymphocytic leukemia (non-CLL leukemia). Vital status was determined for 95.3% of the 12 219 veterans. The dose to red bone marrow was low (mean 3.2 mGy, maximum 500 mGy). Military participants at the PLUMBBOB nuclear test series remained relatively healthy after 53 years and died at a lower rate than the general population. In contrast, and in comparison with national rates, the SMOKY participants showed significant increases in all causes of death, respiratory cancer, leukemia, nephritis and nephrosis, and accidents, possibly related in part to lifestyle factors common to enlisted men who made up 81% of the SMOKY cohort. Compared with national rates, a statistically significant excess of non-CLL leukemia was observed among SMOKY participants (Standardized Mortality Ratio = 1.89, 95% 1.24-2.75, n = 27) but not among PLUMBBOB participants after excluding SMOKY (SMR = 0.87, 95% 0.64-1.51, n = 47). Leukemia risk, initially reported to be significantly increased among SMOKY participants, remained elevated, but this risk diminished over time. Despite an intense dose reconstruction, the risk for leukemia was not found to increase with increasing levels of radiation dose to the red bone marrow. Based on a linear model, the estimated excess relative risk per mGy is -0.05 (95% CI -0.14, 0.04). An explanation for the observed excess of leukemia remains unresolved but conceivably could be related to chance due to small numbers, subtle biases in the study design and/or high tobacco use among enlisted men. Larger studies should elucidate further the possible relationship between fallout radiation, leukemia and cancer among atomic veterans. PMID- 27355259 TI - Cognitive and emotional empathy in typical and impaired readers and its relationship to reading competence. AB - Studies indicate a strong relationship between empathy and language skills, but the relationship between reading and empathy remains elusive, although a shared neural substrate (the temporoparietal junction; TPJ) has been implicated in both reading and empathy. Motivated by these observations, the purpose of the current study was to examine empathic skills in a large spectrum of reading abilities, including typical readers and individuals with dyslexia, and their relationship to reading competence. We administered the Intrapersonal Reactivity Index (IRI) test, which differentiates between two subscales of empathy (cognitive and emotional empathy), to a group of participants with dyslexia and typical readers. Results indicate that the general reading score (average z scores of all reading tests) was significantly positively correlated with empathic scores. In addition, tests of specific reading abilities-decoding, reading fluency, and reading related measures of phonological awareness-were significantly positively correlated with empathic scores. Finally, participants with dyslexia who showed low reading abilities had significantly lower scores in total empathy and cognitive empathy, as measured by the IRI test, than did typical participants with high reading abilities. Taken together, these results indicate a strong association between reading-related skills and empathic abilities and may point to involvement of the TPJ in both empathy and reading. PMID- 27355260 TI - Taming the Electronic Structure of Diradicals through the Window of Computationally Cost Effective Multireference Perturbation Theory. AB - Recently a state-specific multireference perturbation theory (SSMRPT) with an improved virtual orbitals complete active space configuration interaction (IVO CASCI) reference function has been proposed for treating electronic structures of radicals such as methylene, m-benzyne, pyridyne, and pyridynium cation. This new development in MRPT, termed as IVO-SSMRPT, ensures that it is able to describe the structure of radicaloids with reasonable accuracy even with small reference spaces. IVO-SSMRPT is also capable of predicting the correct ordering of the lowest singlet-triplet gaps. Investigation of the first three electronic states of the oxygen molecule has also been used for rating our method. The agreement of our estimates with the available far more expensive benchmark state-of-the-art ab initio calculations is creditable. The IVO-SSMRPT method provides an effective avenue with manageable cost/accuracy ratio for accurately dealing with radicaloid systems possessing varying degrees of quasidegeneracy. PMID- 27355261 TI - Prospective Randomized Controlled Trial of Liberal Vs Restricted Perioperative Fluid Management in Patients Undergoing Pancreatectomy. AB - OBJECTIVE: The aim of this study is to examine, by a prospective randomized controlled trial, the influence of liberal (LIB) vs restricted (RES) perioperative fluid administration on morbidity following pancreatectomy. SUMMARY OF BACKGROUND DATA: Randomized controlled trials in patients undergoing major intra-abdominal surgery have challenged the historical use of LIB fluid administration, suggesting that a more restricted regimen may be associated with fewer postoperative complications. METHODS: Patients scheduled to undergo pancreatic resection were consented for randomization to a LIB (n = 164) or RES (n = 166) perioperative fluid regimen. Sample size was designed with 80% power to decrease Grade 3 complications from 35% to 21%. RESULTS: Between July 2009 and July 2015, we randomized 330 patients undergoing pancreaticoduodenectomy (PD, n = 218), central (n = 16), or distal pancreatectomy (DP, n = 96). Patients were equally distributed for all demographic and intraoperative characteristics. Intraoperatively, LIB patients received crystalloid 12 mL/kg/h and RES patients 6 mL/kg/h. Cumulative crystalloid given (median, range, mL) days 0 to 3 was LIB: 12,252 (6600 to 21,365), RES 7808 (2700 to 16,274) P < 0.0001. Sixty-day mortality was 2 of 330 (0.6%). Median operative time for PD was 227 minutes (105 to 462) and DP 150 (44 to 323). Grade 3 complications occurred in 20% of LIB and 27% of RES patients (P = 0.6). Median length of stay was 7 and 5 days for PD and DP, respectively, in both arms. CONCLUSIONS: In a high volume institution, major perioperative complications from pancreatic resection were not significantly influenced by fluid regimens that differed approximately 1.6-fold. PMID- 27355262 TI - Locally Advanced Pancreatic Cancer: Neoadjuvant Therapy With Folfirinox Results in Resectability in 60% of the Patients. AB - OBJECTIVE: For patients with locally advanced and unresectable pancreatic cancer (PDAC), neodadjuvant treatment and consecutive surgical exploration have been studied during the last decade with various neoadjuvant therapies including chemotherapy and combinations with radiation. Aim of the study was the evaluation of neoadjuvant therapy with a focus on Folfirinox. METHODS: All consecutive patients undergoing surgery for PDAC after neoadjuvant treatment were analyzed (clinico-pathological characteristics, secondary resection rates, outcome). Patients receiving Folfirinox were compared with other treatment regimens. RESULTS: Between December 2001 and June 2015, 575 patients received neoadjuvant treatment and were scheduled for resection after re-staging. A successful resection was achieved in 292 patients (50.8%). Resection rates following Folfirinox were 61% (76/125 patients) compared with 46% (150/322 patients) after gemcitabine and radiation, and 52% (66/128 patients) after other treatments (P = 0.026). Median overall survival was 15.3 months after resection vs 8.5 months after exploration alone (P < 0.0001). Subgroup median survival was 16.0 months (Folfirinox) vs 16.5 months (gemcitabine) and 14.5 months (others) with 3-year survival of 28.1%, 23.2%, and 19.7%, respectively (P = 0.8582). By multivariable analysis, Folfirinox was confirmed to be independently associated with a favorable prognosis. CONCLUSIONS: Folfirinox is a valuable treatment option in the neoadjuvant therapy of PDAC. From the present data, which represent the largest available study population to date, Folfirinox seems to be the most effective protocol resulting in a significantly better secondary resection rate and overall survival than other treatments. It should be considered in all patients fit for this regimen and consecutive surgical exploration. PMID- 27355263 TI - Postoperative 30-day Readmission: Time to Focus on What Happens Outside the Hospital. AB - OBJECTIVE: The aim of this study is to understand the relative contribution of preoperative patient factors, operative characteristics, and postoperative hospital course on 30-day postoperative readmissions. BACKGROUND: Determining the risk of readmission after surgery is difficult. Understanding the most important contributing factors is important to improving prediction of and reducing postoperative readmission risk. METHODS: National Veterans Affairs Surgical Quality Improvement Program data on inpatient general, vascular, and orthopedic surgery from 2008 to 2014 were merged with laboratory, vital signs, prior healthcare utilization, and postoperative complications data. Variables were categorized as preoperative, operative, postoperative/predischarge, and postdischarge. Logistic models predicting 30-day readmission were compared using adjusted R and c-statistics with cross-validation to estimate predictive discrimination. RESULTS: Our study sample included 237,441 surgeries: 43% orthopedic, 39% general, and 18% vascular. Overall 30-day unplanned readmission rate was 11.1%, differing by surgical specialty (vascular 15.4%, general 12.9%, and orthopedic 7.6%, P < 0.001). Most common readmission reasons were wound complications (30.7%), gastrointestinal (16.1%), bleeding (4.9%), and fluid/electrolyte (7.5%) complications. Models using information available at the time of discharge explained 10.4% of the variability in readmissions. Of these, preoperative patient-level factors contributed the most to predictive models (R 7.0% [c-statistic 0.67]); prediction was improved by inclusion of intraoperative (R 9.0%, c-statistic 0.69) and postoperative variables (R 10.4%, c-statistic 0.71). Including postdischarge complications improved predictive ability, explaining 19.6% of the variation (R 19.6%, c-statistic 0.76). CONCLUSIONS: Postoperative readmissions are difficult to predict at the time of discharge, and of information available at that time, preoperative factors are the most important. PMID- 27355264 TI - Practice Patterns and Outcomes After Hospital Admission With Acute Para esophageal Hernia in England. AB - OBJECTIVE: (i) To establish at a national level clinical outcomes from patients presenting with acute para-esophageal hernia (PEH); and (ii) to determine if a hospital volume-outcome relationship exists for the management of acute PEH. BACKGROUND: Currently, no clear guidelines exist regarding the management of acute PEH, and practice patterns are based upon relatively small case series. METHODS: Patients admitted as an emergency for the treatment of acute PEH between 1997 and 2012 were included from the Hospital Episode Statistics database. The influence of hospital volume upon clinical outcomes was analyzed in unmatched and matched comparisons to control for patient age, medical comorbidities, and incidence of PEH hernia gangrene. RESULTS: Over the 16-year study period, 12,441 patients were admitted as an emergency with a PEH causing obstruction or gangrene. Of these, 90.8% patients were admitted with PEH with obstruction in the absence of gangrene and 9.2% with PEH with gangrene. The incidences of 30 and 90 day mortality were 7% and 11.5%, respectively, which did not decrease during the study period. Unmatched and matched comparisons showed, in high-volume centers, there were significant reductions in utilization of emergency surgery (8.8% vs 14.9%; P < 0.0001), 30-day (5.3% vs 7.8%; P < 0.0001), and 90-day mortality (9.3% vs 12.7%; P < 0.0001). Multivariate analysis also confirmed high hospital volume was independently associated with reduced 30 and 90-day mortality from acute PEH. CONCLUSIONS: Acute PEH represents a highly morbid condition, and treatment in high-volume centers provides the appropriate multidisciplinary infrastructure to manage these complex patients reducing associated mortality. PMID- 27355265 TI - Usefulness of Mac-2 Binding Protein Glycosylation Isomer for Prediction of Posthepatectomy Liver Failure in Patients With Hepatocellular Carcinoma. AB - OBJECTIVE: The aim of this study was to evaluate the usefulness of the Mac-2 binding protein glycosylation isomer (M2BPGi) for the prediction of posthepatectomy liver failure (PHLF) in hepatocellular carcinoma (HCC) patients. SUMMARY BACKGROUND DATA: M2BPGi is a novel serum marker of liver fibrosis. The usefulness of M2BPGi for the prediction of PHLF has not been evaluated. METHODS: Clinicopathological data were analyzed in 138 HCC patients who underwent liver resection between August 2011 and November 2014. PHLF was evaluated according to the definition of the International Study Group of Liver Surgery. Performance of preoperative parameters in predicting PHLF was determined using receiver operating characteristic (ROC) analysis. RESULTS: Serum M2BPGi level correlated with the METAVIR fibrosis score. M2BPGi levels of hepatitis C virus (HCV) positive patients were significantly higher than those of HCV-negative patients, even in the same fibrosis stage. PHLF >= Grade B developed in 19 patients (13.8%). The area under the ROC curve (AUROC) of M2BPGi for the prediction of PHLF >= Grade B was 0.71. In multivariate analysis, M2BPGi [odds ratio (OR): 2.08, 95% confidence interval (CI) 1.28-3.55], platelet count (OR: 0.39, 95% CI 0.18-0.80), and resection rate (OR: 2.71, 95% CI 1.46-5.40) were the significant factors associated with PHLF >= Grade B. The AUROC of the PHLF index defined by these factors was 0.81. Notably, in patients with HCV infection, the predictive ability of M2BPGi for PHLF (AUROC 0.85) was the best among the preoperative parameters. CONCLUSIONS: M2BPGi is a useful predictor of PHLF, especially in patients with HCV infection. PMID- 27355266 TI - Tradeoffs Associated With Contralateral Prophylactic Mastectomy in Women Choosing Breast Reconstruction: Results of a Prospective Multicenter Cohort. AB - OBJECTIVE: Assess postoperative morbidity and patient-reported outcomes after unilateral and bilateral breast reconstruction in patients with unilateral breast cancer. BACKGROUND: Relatively little is known about the morbidity associated with and changes in quality of life experienced by patients who undergo contralateral prophylactic mastectomy (CPM) and breast reconstruction. This information would be valuable for decision making in patients with unilateral breast cancer. METHODS: Women undergoing mastectomy and breast reconstruction for unilateral breast cancer were recruited for this prospective observational study. Postoperative complications after implant and autologous breast reconstruction in patients undergoing unilateral or bilateral mastectomy were recorded. Preoperative and 1 year patient-reported outcomes were measured. Univariate tests and logistic regression analyses were performed, studying the effects of reconstructive method, laterality, and risk factors on surgical complication rates, patient satisfaction, and anxiety. RESULTS: We identified 1144 women who underwent either unilateral (47.2%) or bilateral (52.8%) mastectomies with reconstruction. Bilateral autologous (odds ratio 1.73, 95% confidence interval 1.07-2.81) and implant reconstructions (odds ratio 1.73, 95% confidence interval 1.22-2.47) were associated with a higher risk of complications compared with unilateral reconstructions. Baseline anxiety was greater in women who chose bilateral compared with unilateral implant reconstructions (P = 0.001). There was no difference in anxiety levels between groups postoperatively. Postoperatively, women who chose CPM with implant reconstructions were more satisfied with their breasts than women with unilateral reconstructions (P = 0.034). CONCLUSIONS: Although higher postoperative complications were observed after CPM and reconstruction, these procedures were associated with decreased anxiety levels and improved satisfaction with breasts for women who underwent implant reconstructions. PMID- 27355267 TI - Glucose Control in Severely Burned Patients Using Metformin: An Interim Safety and Efficacy Analysis of a Phase II Randomized Controlled Trial. AB - OBJECTIVE: To determine whether metformin can achieve glucose control no worse than insulin (noninferiority) without the danger of hypoglycemia (superiority). In addition, to assess whether metformin has any additional effects on lipolysis and inflammation that will enhance burn recovery (superiority). SUMMARY BACKGROUND DATA: Hyperglycemia and insulin resistance after burn injury are associated with increased morbidity and mortality. Insulin administration improves postburn infections, severity of sepsis, and morbidity, but also causes a 4-5-fold increase in hypoglycemia, which is associated with a 9-fold increase in mortality. METHODS: Severely burned adult patients with burns over 20% total body surface area (TBSA) burn were prospectively randomized in this Phase II clinical trial to either metformin or insulin (standard of care) treatment. Primary outcomes were glucose levels and incidence of hypoglycemia. Secondary outcomes included glucose and fat metabolism, and clinical outcomes. RESULTS: Forty-four patients were enrolled in this Phase II clinical trial, 18 metformin and 26 insulin patients. Demographics, burn size, concomitant injuries, and mortality were comparable between both groups. Metformin controlled blood glucose as equally as insulin with no difference between the 2 treatment groups, P > 0.05. While there was a 15% incidence of hypoglycemia in the insulin group, there was only 1 mild hypoglycemic episode (6%) in the metformin group, P < 0.05. Oral glucose tolerance tests at discharge revealed that metformin significantly improved insulin sensitivity, P < 0.05. Furthermore, metformin had a strong antilipolytic effect after burn injury when compared with insulin and was associated with significantly reduced inflammation, P < 0.05. CONCLUSIONS: Metformin decreases glucose equally as effective as insulin without causing hypoglycemia, with additional benefits including improved insulin resistance and decreased endogenous insulin synthesis when compared with insulin controls. These results indicate that metformin is safe in burn patients and further supports the use of metformin in severely burned patients for postburn control of hyperglycemia and insulin resistance. PMID- 27355268 TI - Effect of Hospital Case Mix on the Hospital Consumer Assessment of Healthcare Providers and Systems Star Scores: Are All Stars the Same? AB - OBJECTIVE: We aimed to evaluate variations in patient experience measures across different surgical specialties and to assess the impact of further case-mix adjustment. BACKGROUND: Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) is a publicly reported survey of patients' hospital experiences that directly influence Medicare reimbursement. METHODS: All adult surgical inpatients meeting criteria for HCAHPS sampling from 2013 to 2014 at a single academic center were identified. HCAHPS measures were analyzed according to published top-box and Star-rating methodologies, and were dichotomized ("high" vs "low"). Multivariable logistic regression was used to identify independent associations of high patient scores on various HCAHPS measures with specialty, diagnosis-related group complexity, cancer diagnosis, sex, and emergency admission after adjusting for HCAHPS case-mix adjusters (education, overall health status, language, and age). RESULTS: We identified 36,551 eligible patients, of which 30.8% (n = 11,273) completed HCAHPS. Women [odds ratio (OR) 0.78, 95% confidence interval (CI) 0.72-0.85, P < 0.001], complex cases (OR 0.90, 95% CI 0.82-0.99, P = 0.02), and emergency admissions (OR 0.67, 95% CI 0.55-0.82, P < 0.001) had lesser Star scores on adjusted analysis, whereas patients with a cancer diagnosis had greater Star scores (OR 1.15, 95% CI 1.03-1.29, P = 0.01). Using general surgery as the reference, the Star scores varied significantly across 12 specialties (range OR 0.65 for plastics to 1.29 for transplant surgery). Patient responses to individual composite scores (pain, care transition, physician, and nurse) varied by specialty. CONCLUSIONS: HCAHPS case mix adjustment does not include adjustment for specialty or diagnosis, which may result in artificially lower scores for centers that provide a high level of complex care. Further research is needed to ensure that the HCAHPS is an unbiased comparison tool. PMID- 27355269 TI - Is Nonoperative Management Warranted in Ventral Hernia Patients With Comorbidities?: A Case-matched, Prospective, Patient-centered Study. AB - OBJECTIVE: The aim of this study was to determine patient-centered outcomes of nonoperative treatment of a ventral hernia. SUMMARY OF BACKGROUND DATA: Nonoperative management of ventral hernias (VHs) is often recommended for patients at increased risk of complications; however, the impact of this management strategy on outcome and quality of life (QoL) is unknown. We hypothesize that QoL and function are better among patients with VHs managed operatively. METHODS: Patients with a VH from a single-center hernia clinic were prospectively enrolled between June 2014 and June 2015. Nonoperative management was recommended if smoking, obesity, or poorly controlled diabetes was present. Primary outcomes were patient-centered outcomes, including QoL and function, which were measured using a validated, hernia-specific survey (modified Activities Assessment Scale) before surgeon' consultation and at 6 months. Other outcomes included surgical site infection (SSI) and recurrence. Risk-adjusted outcomes between nonoperative and operative groups were compared using: paired t test on a propensity score-matched subset and multivariable analysis on the overall cohort. RESULTS: A total of 152 patients (nonoperative = 97, operative = 55) were enrolled. In the propensity-matched cohort (n = 90), both groups had similar baseline QoL and function scores, but only repaired patients had improved scores on 6-month follow-up. In the overall cohort, nonoperative management was strongly associated with lower function scores (log odds ratio = -26.5; 95% confidence interval = -35.0 to -18.0). CONCLUSIONS: This is the first prospective study comparing management strategies in VH patients with comorbidities. Elective repair improves hernia-related QoL and function in low- to moderate-risk patients and should be considered in appropriately selected patients. PMID- 27355270 TI - Equilibrium Dynamics in the Thallium(III)-Cyanide System in Aqueous Solution. PMID- 27355271 TI - Stereocontrolled Synthesis of beta-Lactams within [2]Rotaxanes: Showcasing the Chemical Consequences of the Mechanical Bond. AB - The intramolecular cyclization of N-benzylfumaramide [2]rotaxanes is described. The mechanical bond of these substrates activates this transformation to proceed in high yields and in a regio- and diastereoselective manner, giving interlocked 3,4-disubstituted trans-azetidin-2-ones. This activation effect markedly differs from the more common shielding protection of threaded functions by the macrocycle, in this case promoting an unusual and disfavored 4-exo-trig ring closure. Kinetic and synthetic studies allowed us to delineate an advantageous approach toward beta-lactams based on a two-step, one-pot protocol: an intramolecular ring closure followed by a thermally induced dethreading step. The advantages of carrying out this cyclization in the confined space of a benzylic amide macrocycle are attributed to its anchimeric assistance. PMID- 27355272 TI - PGRMC1 and the faithful progression through mitosis and meiosis. PMID- 27355273 TI - Manipulating Migration Behavior of Magnetic Graphene Oxide via Magnetic Field Induced Casting and Phase Separation toward High-Performance Hybrid Ultrafiltration Membranes. AB - Hybrid membranes blended with nanomaterials such as graphene oxide (GO) have great opportunities in water applications due to their multiple functionalities, but they suffer from low modification efficiency of nanomaterials due to the fact that plenty of the nanomaterials are embedded within the polymer matrix during the blending process. Herein, a novel Fe3O4/GO-poly(vinylidene fluoride) (Fe3O4/GO-PVDF) hybrid ultrafiltration membrane was developed via the combination of magnetic field induced casting and a phase inversion technique, during which the Fe3O4/GO nanocomposites could migrate toward the membrane top surface due to magnetic attraction and thereby render the surface highly hydrophilic with robust resistance to fouling. The blended Fe3O4/GO nanocomposites migrated to the membrane surface with the magnetic field induced casting, as verified by X-ray photoelectron spectroscopy, elemental analysis, and energy dispersive X-ray spectroscopy. As a result, the novel membranes exhibited significantly improved hydrophilicity (with a contact angle of 55.0 degrees ) and water flux (up to 595.39 L m(-2) h(-1)), which were improved by 26% and 206%, 12% and 49%, 25% and 154%, and 11% and 33% compared with those of pristine PVDF membranes and PVDF hybrid membranes blended with GO, Fe3O4, and Fe3O4/GO without the assistance of magnetic field during membrane casting, respectively. Besides, the novel membranes showed high rejection of bovine serum albumin (>92%) and high flux recovery ratio (up to 86.4%). Therefore, this study presents a novel strategy for developing high-performance hybrid membranes via manipulating the migration of nanomaterials to the membrane surface rather than embedding them in the membrane matrix. PMID- 27355276 TI - The Electronic States of U(4+) in U(PO4)Cl: An Example for Angular Overlap Modeling of 5f(n) Systems. AB - Detailed experimental data on UPO4Cl comprising single-crystal UV/vis/NIR spectra and temperature-dependent magnetic susceptibilities form the basis for the investigation of the electronic structure of the U(4+) cation in UPO4Cl. For modeling of the observed physical properties the angular overlap model (AOM) was successfully employed. The computations were performed using the newly developed computer program BonnMag. The calculations show that all electronic transitions and the magnetic susceptibility as well as its temperature dependence are well reproduced within the AOM framework. Using Judd-Ofelt theory BonnMag allows estimation of the relative absorption coefficients of the electronic transitions with reasonable accuracy. Ligand field splitting for states originating from f electron configurations are determined. Slater-Condon-Shortley parameters and the spin-orbit coupling constant for U(4+) were taken from literature. The good transferability of AOM parameters for U(4+) is confirmed by calculations of the absorption spectra of UP2O7 and (U2O)(PO4)2. The effect of variation of the fit parameters is investigated. AOM parameters for U(4+) (5f) are compared to those of the rare-earth elements (4f) and transition metals (3d). PMID- 27355274 TI - Fragile X-associated tremor/ataxia syndrome: another phenotype of the fragile X gene. AB - OBJECTIVE: Neuropsychologists have an important role in evaluating patients with fragile X-associated disorders, but most practitioners are unaware of the recently identified neurodegenerative movement disorder known as fragile X associated tremor ataxia syndrome (FXTAS). The objective of this editorial is to orient the reader to FXTAS and highlight the importance of clinical neuropsychology in describing the fragile X premutation phenotype and the role practitioners may have in assessing and monitoring patients with or at risk for neurodegeneration. METHOD: We issued a call for papers for the special issue, highlighting the primary objective of familiarizing clinical neuropsychologists with FXTAS, and with the neuropsychological phenotype of both male and female asymptomatic carriers. RESULTS: Eight papers are included, including an overview of the fragile X-associated disorders (Grigsby), a review of the neuroradiological and neurological aspects of FXTAS and how the disorder compares to other movement disorders (O'Keefe et al.), a perspective on the prominence of white matter disease and dementia in FXTAS (Filley), and a review of mouse models of FXTAS (Foote). There are four research papers, including one on self-reported memory problems in FXTAS (Birch et al.), and three papers focused on the neuropsychiatric aspects of the fragile X premutation, a review (Bourgeois), an examination of autism-related traits (Schneider), and a research paper on executive functioning and psychopathology (Grigsby). CONCLUSIONS: The issue highlights the importance of awareness of fragile X-associated disorders for neuropsychologists, an awareness that must reach beyond neurodevelopmental aspects related to fragile X syndrome into the realm of neurodegenerative disease and aging. PMID- 27355277 TI - Departmental Workload and Physician Errors in Radiation Oncology. AB - PURPOSE: The purpose of this work was to evaluate measures of increased departmental workload in relation to the occurrence of physician-related errors and incidents reaching the patient in radiation oncology. MATERIALS AND METHODS: All data were collected for the year 2013. Errors were defined as forms received by our departmental process improvement team; of these forms, only those relating to physicians were included in the study. Incidents were defined as serious errors reaching the patient requiring appropriate action; these were reported through a separate system. Workload measures included patient volumes and physician schedules and were obtained through departmental records for daily and monthly data. Errors and incidents were analyzed for relation with measures of workload using logistic regression modeling. RESULTS: Ten incidents occurred in the year. The number of patients treated per day was a significant factor relating to incidents (P < 0.003). However, the fraction of department physicians off-duty and the ratio of patients to physicians were not found to be significant factors relating to incidents. Ninety-one physician-related errors were identified, and the ratio of patients to physicians (rolling average) was a significant factor relating to errors (P < 0.03). The number of patients and the fraction of physicians off-duty were not significant factors relating to errors.A rapid increase in patient treatment visits may be another factor leading to errors and incidents. All incidents and 58% of errors occurred in months where there was an increase in the average number of fields treated per day from the previous month; 6 of the 10 incidents occurred in August, which had the highest average increase at 26%. CONCLUSIONS: Increases in departmental workload, especially rapid changes, may lead to higher occurrence of errors and incidents in radiation oncology. When the department is busy, physician errors may be perpetuated owing to an overwhelmed departmental checks system, leading to incidents reaching the patient. Insights into workload and workflow will allow for the development of targeted approaches to preventing errors and incidents. PMID- 27355278 TI - Cognitive Impairment of School Children at High Altitude: The Case for Oxygen Conditioning in Schools. AB - West, John B. Cognitive impairment of school children at high altitude: the case for oxygen conditioning in schools. High Alt Med Biol. 17:203-207, 2016.-The hypoxia of high altitude frequently affects cognitive function. Recent work has shown that high altitude impairs the neuropsychological function of children of school age when compared with a similar control group of children at low altitude. This implies that the learning process is compromised at high altitude. One option is to bus children down to a lower altitude for schooling, but this is generally impracticable. Recently the new technique of oxygen conditioning has been introduced. The procedure is similar to air conditioning except that instead of altering the temperature of the air, the oxygen concentration is increased, thus raising the PO2 in the inspired air of classrooms. The result is that the children are physiologically at a lower altitude. Just as in very hot or cold climates, it is now unacceptable to have schools that are not air conditioned; in the future the same may apply to schools at high altitude that are not oxygen conditioned. PMID- 27355279 TI - Aroma Effects on Physiologic and Cognitive Function Following Acute Stress: A Mechanism Investigation. AB - OBJECTIVE: Aromas may improve physiologic and cognitive function after stress, but associated mechanisms remain unknown. This study evaluated the effects of lavender aroma, which is commonly used for stress reduction, on physiologic and cognitive functions. The contribution of pharmacologic, hedonic, and expectancy related mechanisms of the aromatherapy effects was evaluated. METHODS: Ninety-two healthy adults (mean age, 58.0 years; 79.3% women) were randomly assigned to three aroma groups (lavender, perceptible placebo [coconut], and nonperceptible placebo [water] and to two prime subgroups (primed, with a suggestion of inhaling a powerful stress-reducing aroma, or no prime). Participants' performance on a battery of cognitive tests, physiologic responses, and subjective stress were evaluated at baseline and after exposure to a stress battery during which aromatherapy was present. Participants also rated the intensity and pleasantness of their assigned aroma. RESULTS: Pharmacologic effects of lavender but not placebo aromas significantly benefited post-stress performance on the working memory task (F(2, 86) = 5.41; p = 0.006). Increased expectancy due to positive prime, regardless of aroma type, facilitated post-stress performance on the processing speed task (F(1, 87) = 8.31; p = 0.005). Aroma hedonics (pleasantness and intensity) played a role in the beneficial lavender effect on working memory and physiologic function. CONCLUSIONS: The observable aroma effects were produced by a combination of mechanisms involving aroma-specific pharmacologic properties, aroma hedonic properties, and participant expectations. In the future, each of these mechanisms could be manipulated to produce optimal functioning. PMID- 27355280 TI - Ultrasonography for Hand and Wrist Conditions. AB - Ultrasonography facilitates dynamic, real-time evaluation of bones, joints, tendons, nerves, and vessels, making it an ideal imaging modality for hand and wrist conditions. Ultrasonography can depict masses and fluid collections, help locate radiolucent foreign bodies, characterize traumatic or overuse tendon or ligament pathology, and help evaluate compressive peripheral neuropathy and microvascular blood flow. Additionally, this modality improves the accuracy of therapeutic intra-articular or peritendinous injections and facilitates aspiration of fluid collections, such as ganglia. PMID- 27355281 TI - Swimmer's Shoulder: Painful Shoulder in the Competitive Swimmer. AB - Swimmer's shoulder is a broad term often used to diagnose shoulder injury in swimmers. However, research has elucidated several specific shoulder injuries that often are incurred by the competitive swimmer. Hyperlaxity, scapular dyskinesis, subacromial impingement, labral damage, os acromiale, suprascapular nerve entrapment, and glenohumeral rotational imbalances all may be included within a differential diagnosis for shoulder pain in the competitive swimmer. An understanding of the mechanics of the swim stroke, in combination with the complex static and dynamic properties of the shoulder, is essential to the comprehension and identification of the painful swimmer's shoulder. It is important for the athlete, coach, and clinician to be aware of the discerning characteristics among these different injuries to ensure a proper diagnosis and treatment plan to aid the swimmer in his or her return to competition. PMID- 27355282 TI - Clinical Outcomes of Surgical Stabilization of Flail Chest Injury. AB - INTRODUCTION: Recent reported success in surgical stabilization of flail chest has been described in small series, but scant evidence exists for this procedure in the orthopaedic literature. METHODS: We reviewed 88 consecutive patients who underwent surgical stabilization of flail chest, along with 88 consecutive patients with flail chest who underwent traditional closed management before initiation of our algorithm change to surgical management. RESULTS: Surgical stabilization of flail chest injuries led to statistically significant decreases in hospital length of stay, ventilator-dependency time, pneumonia, tracheostomy, and mortality rate. In addition, the presence of pulmonary contusion did not eliminate the significant improvements in the aforementioned variables. DISCUSSION: Surgical stabilization of flail chest with modern techniques and implants provides significant improvements in both mortality and short-term outcomes. Although pulmonary contusion decreased overall outcomes across both cohorts, this factor did not alter the ability of rib fixation to improve outcomes. PMID- 27355283 TI - Complications of Primary Total Knee Arthroplasty Among Patients With Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, and Osteoarthritis. AB - BACKGROUND: Although several studies have reported outcomes of primary total knee arthroplasty (TKA) in patients with rheumatoid arthritis, very little has been reported on the outcomes of this procedure in patients with other inflammatory arthritides. METHODS: This study used a national database to evaluate 90-day postoperative complication rates, readmission rates, and revision rates after TKA in patients with inflammatory arthritis. Patients with rheumatoid arthritis (n = 153,531), psoriatic arthritis (n = 7,918), and ankylosing spondylitis (n = 4,575) were compared with patients with osteoarthritis (n = 1,751,938) who underwent TKA from 2005 to 2012. RESULTS: The rates of systemic complications, infection, revision, and 90-day readmission after TKA in patients with different types of inflammatory arthritis were significantly higher than those in control patients with osteoarthritis (P < 0.0001). No differences were found in the rates of systemic or local complications, revision, or readmission among the types of inflammatory arthritis. CONCLUSION: Inflammatory arthritis is associated with increased rates of perioperative complications, revision, and 90-day readmission after primary TKA. LEVEL OF EVIDENCE: Level III. PMID- 27355284 TI - Revision Anterior Cruciate Ligament Reconstruction: Results of a Single-stage Approach Using Allograft Dowel Bone Grafting for Femoral Defects. AB - INTRODUCTION: The purpose of this study was to present results of single-stage revision anterior cruciate ligament (ACL) reconstruction using an allograft bone dowel for isolated femoral bony deficiency. METHODS: Sixteen patients underwent single-stage revision ACL reconstruction using an allograft bone dowel for isolated femoral bony deficiency between 2007 and 2012. Twelve patients (75%) completed study visits, which included CT scans as well as completion of validated outcomes measures. RESULTS: The average KT-1000 side-to-side difference was 1.0 mm +/- 2.9 mm. The average International Knee Documentation Committee score was 70.2 +/- 17.8, the Tegner score was 4.8 +/- 2.8, and the visual analog scale pain score was 2.8 +/- 2.4. An analysis of CT scans showed that all 12 dowels had excellent (>75%) incorporation. CONCLUSIONS: A single-stage approach for revision ACL reconstruction using allograft dowels for isolated femoral bony deficiency yields objective and subjective outcomes comparable to those reported in the literature for two-stage and other single-stage techniques, with good incorporation of the dowels. LEVEL OF EVIDENCE: Retrospective case series, level IV. PMID- 27355285 TI - Treatment of Anterior Cruciate Ligament Injuries. AB - The American Academy of Orthopaedic Surgeons has developed the Appropriate Use Criteria (AUC) document Treatment of Anterior Cruciate Ligament Injuries. Evidence-based information, in conjunction with the clinical expertise of physicians, was used to develop the criteria to improve patient care and obtain the best outcomes while considering the subtleties and distinctions necessary in making clinical decisions. The AUC clinical patient scenarios were derived from patient indications that generally accompany an anterior cruciate ligament injury, as well as from current evidence-based clinical practice guidelines and supporting literature. The 56 patient scenarios and 8 treatments were developed by the Writing Panel, a group of clinicians who are specialists in this AUC topic. Lastly, a separate, multidisciplinary Voting Panel (made up of specialists and nonspecialists) rated the appropriateness of treatment of each patient scenario using a 9-point scale to designate a treatment as Appropriate (median rating, 7 to 9), May Be Appropriate (median rating, 4 to 6), or Rarely Appropriate (median rating, 1 to 3). PMID- 27355286 TI - Surgical Management of Osteoarthritis of the Knee: Evidence-based Guideline. AB - Surgical Management of Osteoarthritis of the Knee: Evidence-based Guideline is based on a systematic review of the current scientific and clinical research. The guideline contains 38 recommendations pertaining to the preoperative, perioperative, and postoperative care of patients with osteoarthritis (OA) of the knee who are considering surgical treatment. The purpose of this clinical practice guideline is to help improve surgical management of patients with OA of the knee based on current best evidence. In addition to guideline recommendations, the work group highlighted the need for better research on the surgical management of OA of the knee. PMID- 27355287 TI - AAOS Clinical Practice Guideline: Surgical Management of Osteoarthritis of the Knee: Evidence-based Guideline. PMID- 27355288 TI - The challenges of USA nursing education to meet local, regional and global need. PMID- 27355289 TI - Nurses' knowledge and practice on social participation in health. AB - OBJECTIVE: to identify nurses' knowledge and practice in the framework of the Family Health Strategy program with regard to social participation in health. METHOD: qualitative study which had the Family Health Units in a municipality of Minas Gerais as setting. Nine nurses participated in the study, and they were interviewed individually in July and August 2014. Data were collected and analyzed according to the content analysis technique and interpreted in the light of Paulo Freire's ontology and critical pedagogy. RESULTS: the analyzed statements showed that nurses bring along conceptual and behavioral inconsistencies which need to be equalized, so their knowledge and practice can mediate the challenging construction of participatory management in health. CONCLUSION: an improvement in nurses' training is suggested, both academically and professionally, aiming at strengthening their political role in the process of consolidation of social participation in the Brazilian Unified Health System. PMID- 27355290 TI - "To be a nurse": a professional choice and the construction of identity processes in the 1970s. AB - OBJECTIVE: to analyze the factors that influenced the choice for nursing made by graduates from the first class of the Undergraduate Nursing and Obstetrics Course of the Federal University of Rio Grande do Norte in the 1970s and to understand the senses and meanings of being a nurse when choosing this profession. METHOD: a qualitative socio-historical study was performed, using oral history to collect data. RESULTS: the analysis generated the following categories: "To be a nurse: a professional choice" and "The ideal of being a nurse: senses and meanings". The senses of "being a nurse" are associated with graduates' perspective of this profession and the meanings included the traditional conceptions that have historically affected it. CONCLUSION: professional choice was influenced by family and work expectations and the nursing course had an effect on the construction of nurses' professional identity. PMID- 27355291 TI - Prevalence and factors associated with frailty in non-institutionalized older adults. AB - OBJECTIVE: to investigate the prevalence and factors associated with frailty in non-institutionalized older adults living in northern Minas Gerais, Brazil. METHOD: data were collected in their homes, in 2013, based on a census cluster sampling. Demographic and socioeconomic variables, morbidities, utilization of health care services, and scores on the Edmonton Fragility Scale were analyzed. The adjusted prevalence ratios were obtained using the Poisson regression multiple analysis with robust variance. RESULTS: the prevalence of frailty was 41.3%. The variables associated with frailty were: female gender, very old age, education of less than four years, not having been hospitalized in the last 12 months, having a caregiver, falling in the prior year, diabetes mellitus, cardiac disease, and osteoarticular disease. CONCLUSION: the prevalence of frailty was high. Some factors consist of modifiable conditions, which should encourage health actions aimed at this group. PMID- 27355292 TI - Health status and the return to work after traffic accidents. AB - OBJECTIVE: to compare the health status of traffic accident victims, at hospital discharge and after six months, and to analyze the predictive variables of their health status and return to work. METHOD: observational, longitudinal study. Data were collected through interviews and medical records of 102 patients with a mean age of 33 years; with the majority being men and victims of motorcycle accidents. The variables were analyzed by means of validated tools, student's t-test, multiple linear regression, and logistic regression. RESULTS: there was an improvement of perception in the patients' health status six months after hospital discharge and functional capacity. The individuals who returned to work showed better health-related quality of life evaluation. CONCLUSION: improvement of the perceived health status six months after hospital discharge was found. Factors that influenced the patients' return to work were not identified. PMID- 27355293 TI - Accreditation in a public hospital: perceptions of a multidisciplinary team. AB - OBJECTIVE: to analyze the perceptions of the multidisciplinary team on Accreditation in a public hospital. METHOD: descriptive, exploratory, qualitative research, performed in May 2014, using recorded individual interviews. In total, 28 employees of a public hospital, Accredited with Excellence, answered the guiding question: "Tell me about the Accreditation system used in this hospital". The interviews were transcribed and subjected to content analysis. RESULTS: of the speeches, three categories emerged: Advantages offered by the Accreditation; Accredited public hospital resembling a private hospital; Pride/satisfaction for acting in an accredited public hospital. CONCLUSION: participants perceived Accreditation as a favorable system for a quality management in the public service because it promotes the development of professional skills and improves cost management, organizational structure, management of assistance and perception of job pride/satisfaction. PMID- 27355294 TI - Pressure ulcers in critically ill patients: incidence and associated factors. AB - OBJECTIVE: to identify the incidence and describe the associated factors for pressure ulcers in critically ill patients. METHOD: this was a prospective cohort study with 77 patients, using a clinical, metabolic assessment and the associated factors for pressure ulcer, applying the risk scales (Braden and Waterlow) and assigning ulcers to categories. RESULTS: an incidence of 22% (95% CI 12.6 - 31.5), with 17 patients with 32 pressure ulcers in the sacral region (47%), and of Class I (72%). The length of stay was greater than ten days (71%), most admissions were surgical (53%) or for congestive heart failure (24%), and were high risk on the Braden Scale (59%). CONCLUSION: the study highlights the high incidence of pressure ulcers, clinical and metabolic characteristics and associated factors, as well as the outcome of death, requiring, therefore, preventive measures. PMID- 27355295 TI - Impact of home visits on the functional capacity of patients with venous ulcers. AB - OBJECTIVE: to assess the impact of protocol home visits on the functional capacity of adult and elderly patients with venous ulcers, before and after guidance received at home. METHOD: clinical experimental, randomized, nonblinded and controlled study, developed with 32 patients (case and control groups). Fields of research were the Wound Outpatient Care Unit of the Antonio Pedro University Hospital and households of patients treated in the outpatient unit. Data collection occurred from February to June 2014, by means of an assessment tool of the health care unit, the TINETTI index and a script for directions to be provided to study participants who received home visits. RESULTS: participants in the case group showed significant and differentiated improvement post intervention when compared to the control group, which remained stable. CONCLUSION: directions provided in the home context were beneficial to the members of the case group. PMID- 27355296 TI - Frailty and quality of life in elderly primary health care users. AB - OBJECTIVE: to investigate the association between physical frailty and quality of life in elderly users of primary health care in the capital of the state of Parana. METHOD: a cross-sectional, quantitative study with 203 elders. Data collected included: physical activity questionnaires, weight loss, fatigue/exhaustion, quality of life, performance of gait speed tests, and handgrip strength. RESULTS: of the 203 older adults, 115 were pre-frail, 49 were non-frail, and 39 were frail, with a significant association with functional capacity and quality of life in all groups. The dimensions resulting from physical aspects, pain, and vitality were associated with those that were non frail. CONCLUSION: in this study, frailty syndrome was inversely proportional to the quality of life, and significantly associated with functional capacity of older adults. Physical frailty is a manageable condition which can be targeted through geriatric nursing interventions. PMID- 27355297 TI - Social impairment of patients undergoing hematopoietic stem cell transplant. AB - OBJECTIVE: to evaluate the impairment of social and emotional domains of hospitalized patients undergoing hematopoietic stem cells transplantation. METHOD: an observational, longitudinal study with 25 participants evaluated in the period of pre-transplant, pancytopenia and pre-hospital discharge between September 2013 and September 2014, in a reference hospital for this treatment modality in Brazil. Two international instruments were used, both of which translated and adapted to Portuguese (Brazil): Quality of Life Questionnaire-Core 30 and Functional Assessment Cancer Therapy - Bone Marrow Transplantation. RESULTS: patients have shown a statistically significant decrease in the social domain, and stability of the emotional function along the course of treatment. CONCLUSION: hematopoietic stem cell transplantation changes the social function of patients with hematologic cancer during hospitalization stage. Thus, patients should receive guidance addressing the social domain in order that it can be less affected. PMID- 27355298 TI - Knowledge management in Portuguese healthcare institutions. AB - Knowledge management imposes itself as a pressing need for the organizations of several sectors of the economy, including healthcare. OBJECTIVE: to evaluate the perception of healthcare institution collaborators in relation to knowledge management in the institution where they operate and analyze the existence of differences in this perception, based on the institution's management model. METHOD: a study conducted in a sample consisting of 671 collaborators from 10 Portuguese healthcare institutions with different models of management. In order to assess the knowledge management perception, we used a score designed from and based on items from the scores available in the literature. RESULTS: the perception of moderate knowledge management on the healthcare institutions and the statistically significant differences in knowledge management perception were evidenced in each management model. CONCLUSION: management knowledge takes place in healthcare institutions, and the current management model determines the way staff at these institutions manage their knowledge. PMID- 27355299 TI - Association between self-care and hospital readmissions of patients with heart failure. AB - OBJECTIVE: to assess the association between self-care and the number of hospital readmissions of patients with heart failure (ADHF) and test the applicability of two self-care assessment tools. longitudinal study, performed in a cardiology reference hospital in southern Brazil. METHOD: it included 82 patients with a mean age of 61.85+/-12.33 years, 57.3% male. The mean score of self-care assessment found the scales European Heart Failure Self-care Behavior Scale and Self-care Scale for Patients with Heart Failure was unsatisfactory. RESULTS: it was observed an average of 2.57+/-1.66 rehospitalization last year for decompensated heart failure. There was a correlation between self-care scores with the number of hospital readmissions for decompensated HF. Education and age were associated to self-care of HF patients. CONCLUSION: both scales assess self care in a relevant way, and correlated their indexes. PMID- 27355300 TI - Notification of health problems among nursing workers in university hospitals. AB - OBJECTIVE: to identify the health problems of nursing workers and describe their consequences. METHOD: an epidemiological, descriptive study with a quantitative approach. The survey was conducted through the Health Monitoring System for Nursing Workers (SIMOSTE) in three university hospitals in Sao Paulo within a 12 month period. RESULTS: a total of 970 records related to health problems were identified; most of these were related to sick leave, occupational accidents with leave, absences, and occupational accidents without leave, with a predominance of musculoskeletal and respiratory system diseases, infectious and parasitic diseases, and nervous system diseases, among others. A total of 4,161 days of work were lost because of the mentioned health problems. CONCLUSION: the results evidence the need to propose preventive strategies to mitigate and reduce health problems in nursing workers. PMID- 27355301 TI - Nursing care in Specialized HIV/Aids Outpatient Services. AB - OBJECTIVE: to analyze the discourses about the care provided by nurses operating in Specialized HIV/Aids Outpatient Services in four public institutions of the city of Fortaleza, Ceara, Brazil. METHOD: descriptive and exploratory study with a qualitative approach, which used as a method the discourse analysis. RESULTS: when titling the "care as negative", such title came from the analogy proposed by Freud (1912) with the photographic negative, represented by what that care can configure from the unconscious movement, since nurses did not perceive themselves in the care actions developed by supporting the work of other occupational categories, contributing to maintain the ideology of biomedicine. CONCLUSION: it is necessary to justify and theorize a nursing clinical practice from epistemological issues of the profession, in such a way that nurses can understand their relevance within the care provided. PMID- 27355302 TI - Health care for children and adolescents with HIV: a comparison of services. AB - OBJECTIVE: compare the quality of different types of health care for children and adolescents with HIV, in the experience of family members and caregivers. METHOD: a cross-sectional study was conducted with 71 family members and caregivers, using the children's version of the Primary Care Assessment Tool (PCATool Brazil). The Mann-Whitney or Student's t-test and Pearson's chi-square or Fisher's exact test were used for the analysis. RESULTS: primary care services and, predominantly, specialized HIV services, were identified as the regular health care sources. There were no significant differences in quality, since their scores were close to the ideal level. CONCLUSION: the attributes of these services need to be improved, which would entail reformulating their structural and performance aspects. In addition, it is imperative to recognize primary health care as an integral place for promoting the health of children and adolescents with HIV. PMID- 27355303 TI - Social representations of nurses on tuberculosis. AB - OBJECTIVE: to describe the social representation of nurses on tuberculosis and identify the implications on nursing care. METHOD: qualitative research with the participation of 52 nurses from 23 Basic Health Units of Belem, Para. A semi structured interview was conducted with subsequent analysis of the thematic content according to the Theory of Social Representations. RESULTS: the social representations of tuberculosis were organized into two categories: infection, evidencing the clinical-epidemiological aspects of the disease, and stigma and prejudice, representing the social aspect. Care is affected by fear - a fact that explains the distance adopted by some nurses when handling ill people. CONCLUSION: the social representations of nurses on tuberculosis remain grounded in fear, leading professionals to keep a certain distance from patients and generating stigma and prejudice, which may affect adherence to treatment. PMID- 27355304 TI - The experience of family care in transitional support houses. AB - OBJECTIVE: to present the theoretical model that represents the experience of care in transitional homes of support to families of children in a period of post transplantation of hematopoietic stem cells. METHOD: grounded theory, performed with 18 participants from three different samples. For analysis, we used the QSR Nvivo10 software. RESULTS: we elaborated four categories: living in the transitional support home; experiencing care of children in post-transplantation of hematopoietic stem cells; taking care of the family caregiver; and returning to a new life at home, which interrelate according to the theoretical code of the interactive family. CONCLUSION: this research contributes to understanding the experience of care in transitional support homes of families with children in post-transplantation of hematopoietic stem cells and subsidizes nursing and health actions provided to this population; it also contributes to the development of a hospital discharge guidance and care directed to this clientele. PMID- 27355305 TI - Moments for hand hygiene in Material and Sterilization Center. AB - OBJECTIVE: to characterize the moments when there is a need for hand hygiene (HH) by employees who work in Material and Sterilization Center (MSC). METHOD: we conducted a descriptive cross-sectional study in the MSC of a large hospital, from July to November 2012, in Goiania, state of Goias, Brazil. Data obtained through observation of workers, following a previously evaluated and tested checklist. RESULTS: to the dirty area, standardized moments of HH were enough. In the clean area, "Extra moments with indication" for HH, resulting from the work process, such as: after disinfecting benches, after verification and inventory of consigned products, before assembling boxes/trays, before loading and unloading the autoclave, before handling and distributing health care products, among others, were necessary. CONCLUSION: the moments of HH in the dirty area coincide with indications of the clinical practice; and, in the clean area, characteristic moments of the work process were captured. PMID- 27355306 TI - Knowledge of healthcare professionals on the evaluation and treatment of neonatal pain. AB - OBJECTIVE: to identify knowledge of healthcare professionals on the management, evaluation and treatment of pain in a neonatal unit in a municipality of Rio de Janeiro. METHOD: descriptive, exploratory study with quantitative analysis. Data were analyzed using the software R. Core Team Results: of the 96 healthcare professionals who participated in the study, 42 nursing aides/technicians responded, along with 22 nurses, 20 physicians and 2 physical therapists. The results showed that 40.5% of the nursing aides/technicians, 50% of the physicians and 50% of the physical therapists confirmed that they coordinate/perform/assist in the care of babies' pain while performing procedures (lumbar puncture, chest tube insertion and central line). There was a significant difference of agreement in relation to the nursing aides/technicians and physicians. Most (69.8%) of the healthcare professionals knew of some non-pharmacological measure effective for relief of acute pain. CONCLUSION: there is a need for an educational intervention program, with participation of those involved, in the process to change professional practice. PMID- 27355307 TI - The experience of grandmothers of children with cancer. AB - OBJECTIVE: to understand, from grandmothers' perspectives, the experience of having a grandchild with cancer. METHOD: qualitative study, guided by philosophical hermeneutics. Eight grandmothers of children who had finished an oncology treatment participated in this study. Data were collected through interviews, which were recorded, transcribed, and analyzed according to the principles of hermeneutics. RESULTS: the grandmothers underwent an experience of multiplied, silent, transformative, and permanent suffering. They believe it is their role to be present, but they recognize their adult children's independence and self-determination. Grandmothers highlighted that their experience has been very little accessed and considered by health care professionals. CONCLUSION: we recommend including grandparents in the context of care and in additional research. PMID- 27355308 TI - Lack of anticipated support for care for community-dwelling older adults. AB - OBJECTIVE: to identify the factors associated with lack of anticipated support for care for community-dwelling older adults. METHOD: this study presents comparison and logistic regression analyses of data from 671 individuals who took part of the multicentric study entitled "Frailty in older Brazilians" - a quantitative, epidemiologic and transversal investigation carried out between 2008 and 2009. RESULTS: the subjective evaluation of anticipated support for care for community-dwelling older adults was a good indicator of risk for lack of anticipated support for care in women, older adults who live alone and those with poor self-rated health. CONCLUSION: it is necessary to reflect upon the formal support system currently available for older people in Brazil, considering that those who most frequently presented lack of anticipated support for care are an increasing population. The study also highlights the importance of using subjective methods for the evaluation of the adequacy of older adults' support network. PMID- 27355309 TI - Patients with HIV/Aids and ulcer risk: nursing care demands. AB - OBJECTIVE: to analyze the demand for nursing care and the risk of pressure ulcers (PU) of patients with HIV/Aids. METHOD: quantitative survey, carried out from December 2012 to March 2013 in a public hospital of Teresina, state of Piaui, Brazil. RESULTS: the sample of 31 patients was predominantly male, mean age 36.6 years, average care demand 49.4%, most showing some risk of developing PU. The variables correlated with PU risk were care demand and clinical outcome (death). Those associated with care demand were age and clinical outcome (death). CONCLUSION: the results showed that patients require moderate nursing care needs and most of them present risk of developing PU. PMID- 27355310 TI - Educational technologies to encourage (self) care in postpartum women. AB - OBJECTIVE: to evaluate national and international literature regarding the use of educational technologies to encourage self care in postpartum women. METHOD: an integrative review of the literature. The articles were collected from the CINAHL, SCOPUS, PubMed, SciELO, LILACS and Cochrane databases; the time period for the articles referred to January/2004 to July/2014; the languages used in the articles were Portuguese, English, Spanish and French; the articles were selected from the following descriptors: postpartum care period, educational technology, nursing and self care. Twenty-seven articles were selected for analysis Results: based on the information found, the scales, counseling and home visits were among the most recommended educational technologies. CONCLUSION: the technologies promote communication, but are sometimes dependent on computer and internet access, which hinder their use by low-income women. PMID- 27355311 TI - Palliative care and spirituality: an integrative literature review. AB - OBJECTIVE: to analyze scientifi c articles published in international online journals about palliative care and spirituality. METHODS: an integrative literature review with data collected in September 2014 from the LILACS, SCIELO, MEDLINE/PubMed, and IBECS databases. RESULTS: thirty-nine publications were identifi ed and their textual analysis facilitated through four thematic approaches: the meaning of spirituality in the context of palliative care; palliative care and spiritual support; spirituality and relief of pain and other symptoms in patients under palliative care; and instruments to evaluate the spiritual dimension of the scope of palliative care. CONCLUSION: this study examined the relevance of the spiritual dimension in the care of patients with palliative care and the need for developing new studies to disseminate knowledge about this topic. DESCRIPTORS: Palliative Care; Palliative Care at End of Live; Spirituality; Religion; Health. PMID- 27355312 TI - Effects from acupuncture in treating anxiety: integrative review. AB - OBJECTIVE: to evaluate the scientific evidence that is available in the literature on the effects of acupuncture for treating anxiety and on the quality of such studies. METHOD: the study is an integrative review of CINAHL, LILACS, PUBMED-PICO, SciELO, and The Cochrane Library between 2001 and 2014. Keywords anxiety, acupuncture therapy, acupuncture, and anxiety disorders were combined among themselves to ensure a wide search of primary studies. RESULTS: among 514 articles, 67 were selected to be fully read and 19 were included. Among these, 11 were found to have strong evidence levels. Among the six articles about randomized clinical studies, five were found to be of reasonable quality. Two studies used acupuncturist nurses to perform their interventions. Its results showed positive and statistically significant effects from using acupuncture for treating subjects with anxiety. CONCLUSION: acupuncture seems to be a promising treatment for anxiety; however, there is a need for improving the methodological quality of the research on this field. PMID- 27355313 TI - The importance of civilian nursing organizations: integrative literature review. AB - OBJECTIVE: to identify and analyze evidence from studies about the importance of civilian nursing organizations. METHOD: an integrative literature review, for which searches were conducted in the databases LILACS, PubMed/MEDLINE, SciELO, BDENF, and Scopus. RESULTS: sixteen articles published between the years 2004 2013 were selected, 68.75% of which were sourced from Brazilian journals and 31.25% from American journals. CONCLUSION: civilian nursing organizations are important and necessary, because they have collaborated decisively in nursing struggles in favor of the working class and society in general, and these contributions influence different axes of professional performance. PMID- 27355315 TI - A human source for ELF magnetic perturbations. AB - Current models that frame consciousness in terms of electromagnetic field theory carry implications that have yet to be fully explored. Endogenous weak extremely low frequency (ELF) magnetic fields are generated by ionic charge flow in axons, dendrites and synaptic transmitters. Because neural tissues are transparent to such fields, these provide the basis for the globally unifying qualities required to properly describe consciousness as a field. At the same time, however, an electromagnetic approach predicts partial transmission of this 1-100 nT field, suggesting external interactions similar to the various ELF magnetic perturbations that are linked to homeostatic and endocrine-related physiological effects. It follows that humans may represent an additional, previously unrecognized source of weak (1-10 nT) ambient ELF magnetic fields. PMID- 27355316 TI - SMARCAL1 and telomeres: Replicating the troublesome ends. AB - DNA replication is constantly challenged by both endogenous and exogenous sources of replication stress. SMARCAL1, an SNF2 family DNA translocase, functions in the DNA damage response to address these obstacles and promote the completion of replication. Most studies examining the function of SMARCAL1 and related enzymes have relied on the addition of exogenous genotoxic agents, but SMARCAL1 is needed even in the absence of these drugs to maintain genome stability during DNA replication. We recently determined that SMARCAL1 functions to limit DNA damage during replication of difficult-to-replicate telomere sequences. SMARCAL1 deficient cells display several markers of telomere instability including extrachromosomal telomere circles and co-localization with DNA damage markers. Furthermore, cells lacking the highly related proteins ZRANB3 and HLTF do not exhibit similar problems suggesting a unique function for SMARCAL1. These studies identified the first source of endogenous replication stress that SMARCAL1 resolves and provide insight into the mechanism of SMARCAL1 function in maintaining genome stability. PMID- 27355318 TI - The MRI features of placental adhesion disorder-a pictorial review. AB - Placental adhesion disorder (PAD) comprises placenta accreta, increta and percreta lesions; these are classified according to the depth of uterine invasion. Although PAD is considered a rare condition, its incidence has increased 10-fold in the last 50 years. Ultrasound is the primary imaging modality for the assessment of the placenta and in the majority of cases, it is sufficient for diagnosis; however, when ultrasound findings are suspicious or inconclusive, MRI is recommended as an adjunct imaging technique. Numerous MRI features of PAD have been described, including dark intraplacental bands, disorganized intraplacental vascularity and abnormal uterine bulging. This pictorial review describes and illustrates these characteristics and discusses their implications in planning delivery. In addition, we present a series of "pitfall" cases to aid the interpreting radiologist and discuss management of PAD. PAD is a clinical and diagnostic challenge that is encountered with increasing frequency, requiring a cohesive multidisciplinary approach to its management. PMID- 27355319 TI - Biomechanical Analysis of a Novel Prosthesis Based on the Physiological Curvature of Endplate for Cervical Disc Replacement. AB - STUDY DESIGN: Biomechanical analysis of a novel prosthesis based on the physiological curvature of endplate was performed. OBJECTIVE: To compare the biomechanical differences between a novel prosthesis based on the physiological curvature of the endplate and the Prestige LP prosthesis after cervical disc replacement (CDR). SUMMARY OF BACKGROUND DATA: Artificial disc prostheses have been widely used to preserve the physiological function of treated and adjacent motion segments in CDR, while most of those present a flat surface instead of an arcuate surface which approximately similar to anatomic structures in vivo. We first reported a well-designed artificial disc prosthesis based on the physiological curvature of the endplate. METHODS: Three motion segments of 24 ovine cervical spines (C2-5) were evaluated in a robotic spine system with axial compressive loads of 50N. Testing conditions were as follows: 1) intact, 2) C3-4 CDR with artificial disc prosthesis based on the physiological curvature of the endplate, and 3) C3-4 CDR with the Prestige LP prosthesis. The range of motion (ROM) and the pressures on the inferior surface of the two prostheses were recorded and analyzed. RESULTS: As compared to the intact state, the ROM of all three segments had no significant difference in the replacement group. Additionally, there was no significant difference in ROM between the two prostheses. The mean pressure on the novel prosthesis was significantly less than the Prestige LP prosthesis. CONCLUSION: ROM in 3 groups (intact group, CDR group with novel prosthesis and CDR group with Prestige LP) showed no significant difference. The mean pressure on the inferior surface of the novel prosthesis was significantly lower than the Prestige LP prosthesis. Therefore, the novel artificial disc prosthesis is feasible and effective, and can reduce the implant bone interface pressure on the endplate, which may be one possible reason of prosthesis subsidence. PMID- 27355320 TI - Impact of Patients' Communication with the Medical Practitioners, on Their Adherence Declared to Preventive Behaviours, Five Years after a Coronary Angiography, in Luxembourg. AB - BACKGROUND: Patients of the National Institute of Cardiac Surgery and Interventional Cardiology in Luxembourg who underwent coronary angiography were surveyed for hypertension, hypercholesterolemia, diabetes and overweight/obesity between 2008/9 and 2013/4. For each cardiovascular risk factor (CVRFs), we analysed the associations between the quality of the patients' communication with the medical practitioner and their adherence declared to preventive behaviours. METHODS: 1,289 completed a self-administered questionnaire on communication with the medical practitioner (P'Com-5 items scale; Cronbach 0.87). 61.8% stopped smoking, 57.9% reduced or stopped their consumption of salt, 71.9% of fat, and 62.8% of sugar, and whereas 65% increased their consumption of fruit and vegetables and 19.8% increased their physical activity. Around 37% reported having made changes following their doctor's advice. 90% were followed by a cardiologist and 95.9% by an attending physician. RESULTS: No link was observed between declaration of physical activity, smoking, fats, and quality of communication. Significant associations: for increased consumption of fruit and vegetables was linked with the quality of doctor-patient communication when patients were overweight (OR = 1.081), obese (OR = 1.130), hypercholesterolemic (OR = 1.102), hypertensive (OR = 1.084) or diabetic (OR = 1.103). Reduction in salt intake was linked only to patients with hypertension (OR = 1.102), whereas reduction or cessation of sugar consumption was linked to overweight (OR = 1.093), and more so obese, (OR = 1.106), hypercholesterolemics (OR = 1.103) and diabetics (OR = 1.173). CONCLUSIONS: Good doctor-patient communication was related to nutrition, particularly increased consumption of fresh fruits and vegetables. Accurate perception of CVRFs by both patients and medical practitioners is essential for CV protection. The aim of instructing patients is to encourage them to make informed decisions about how to change their lifestyle. In routinely, P'Com-5 scale can collect data to assess the improvement of the professional skills. It can be used in medical training to enhance the quality of the therapeutic communication, especially for nutritional coaching, and to evaluate its efficacy in reducing CVRFs. PMID- 27355321 TI - Correction: Association between Psoriasis Vulgaris and Coronary Heart Disease in a Hospital-Based Population in Japan. AB - [This corrects the article DOI: 10.1371/journal.pone.0149316.]. PMID- 27355322 TI - Robust Bayesian Fluorescence Lifetime Estimation, Decay Model Selection and Instrument Response Determination for Low-Intensity FLIM Imaging. AB - We present novel Bayesian methods for the analysis of exponential decay data that exploit the evidence carried by every detected decay event and enables robust extension to advanced processing. Our algorithms are presented in the context of fluorescence lifetime imaging microscopy (FLIM) and particular attention has been paid to model the time-domain system (based on time-correlated single photon counting) with unprecedented accuracy. We present estimates of decay parameters for mono- and bi-exponential systems, offering up to a factor of two improvement in accuracy compared to previous popular techniques. Results of the analysis of synthetic and experimental data are presented, and areas where the superior precision of our techniques can be exploited in Forster Resonance Energy Transfer (FRET) experiments are described. Furthermore, we demonstrate two advanced processing methods: decay model selection to choose between differing models such as mono- and bi-exponential, and the simultaneous estimation of instrument and decay parameters. PMID- 27355317 TI - A Track Record on SHOX: From Basic Research to Complex Models and Therapy. AB - SHOX deficiency is the most frequent genetic growth disorder associated with isolated and syndromic forms of short stature. Caused by mutations in the homeobox gene SHOX, its varied clinical manifestations include isolated short stature, Leri-Weill dyschondrosteosis, and Langer mesomelic dysplasia. In addition, SHOX deficiency contributes to the skeletal features in Turner syndrome. Causative SHOX mutations have allowed downstream pathology to be linked to defined molecular lesions. Expression levels of SHOX are tightly regulated, and almost half of the pathogenic mutations have affected enhancers. Clinical severity of SHOX deficiency varies between genders and ranges from normal stature to profound mesomelic skeletal dysplasia. Treatment options for children with SHOX deficiency are available. Two decades of research support the concept of SHOX as a transcription factor that integrates diverse aspects of bone development, growth plate biology, and apoptosis. Due to its absence in mouse, the animal models of choice have become chicken and zebrafish. These models, therefore, together with micromass cultures and primary cell lines, have been used to address SHOX function. Pathway and network analyses have identified interactors, target genes, and regulators. Here, we summarize recent data and give insight into the critical molecular and cellular functions of SHOX in the etiopathogenesis of short stature and limb development. PMID- 27355323 TI - Quality of Life and Social Functioning during Treatment of Recent Hepatitis C Infection: A Multi-Centre Prospective Cohort. AB - AIM: Despite effective treatment for recent hepatitis C (HCV) infection, side effects and adherence concerns limit its use among people who inject drugs (PWID). This study evaluated health-related quality of life (HRQoL) and social functioning following infection and during recent HCV treatment. METHODS: The Australian Trial of Acute Hepatitis C studied the natural history and treatment of recent HCV infection. HRQoL (SF-12v2) and social functioning (Opiate Treatment Index score) were measured over 48 weeks and their impact on treatment uptake, adherence and virological response were assessed. RESULTS: Of 163 participants, 111 received treatment (HCV n = 74, SVR 55%; HCV/HIV n = 37, SVR 74%). 116 (71%) were male, 124 (76%) ever injected drugs, with 55 (36%) injecting recently and 28/55 (51%) reported needle/syringe sharing. At baseline, median physical and mental HRQoL was 54 units (IQR 46-58) and 46 (35-54) (reference median: 50), respectively, and median social functioning score was 11 units (7-17). Higher social function (<10 vs >=15) predicted increased treatment uptake (AOR 3.43, 95%CI 1.01-11.6, p = 0.048) and higher SVR (AOR 5.11, 95%CI 1.30-20.15, p = 0.020). After adjustment, treated participants had lower physical (-4.90 units, 95%CI -6.33 to -3.48, p<0.001) and mental HRQoL (-3.7 units, 95%CI -5.55 to 1.86, p<0.001) at on-treatment visits, but HRQoL returned to baseline levels during follow-up. CONCLUSIONS: Social functioning can predict recent HCV treatment uptake and SVR. Efforts to maximise social stability may improve treatment response. Pegylated-interferon treatment is associated with reduced HRQoL on-treatment in an already vulnerable population of PWID that would be better served by interferon-free regimens particularly in treated target at PWID to prevent transmission. TRIAL REGISTRATION: ClinicalTrials.gov NCT00192569. PMID- 27355324 TI - N-Ethylmaleimide Sensitive Factor (NSF) Inhibition Prevents Vascular Instability following Gram-Positive Pulmonary Challenge. AB - BACKGROUND: The Acute Respiratory Distress Syndrome (ARDS), remains a significant source of morbidity and mortality in critically ill patients. Pneumonia and sepsis are leading causes of ARDS, the pathophysiology of which includes increased pulmonary microvascular permeability and hemodynamic instability resulting in organ dysfunction. We hypothesized that N-ethylmaleimide sensitive factor (NSF) regulates exocytosis of inflammatory mediators, such as Angiopoietin 2 (Ang-2), and cytoskeletal stability by modulating myosin light chain (MLC) phosphorylation. Therefore, we challenged pulmonary cells, in vivo and in vitro, with Gram Positive bacterial cell wall components, lipoteichoic acid (LTA), and peptidoglycan (PGN) and examined the effects of NSF inhibition. METHODS: Mice were pre-treated with an inhibitor of NSF, TAT-NSF700 (to prevent Ang-2 release). After 30min, LTA and PGN (or saline alone) were instilled intratracheally. Pulse oximetry was assessed in awake mice prior to, and 6 hour post instillation. Post mortem, tissues were collected for studies of inflammation and Ang-2. In vitro, pulmonary endothelial cells were assessed for their responses to LTA and PGN. RESULTS: Pulmonary challenge induced signs of airspace and systemic inflammation such as changes in neutrophil counts and protein concentration in bronchoalveolar lavage fluid and tissue Ang-2 concentration, and decreased physiological parameters including oxygen saturation and pulse distention. TAT-NSF700 pre treatment reduced LTA-PGN induced changes in lung tissue Ang-2, oxygen saturation and pulse distention. In vitro, LTA-PGN induced a rapid (<2 min) release of Ang 2, which was significantly attenuated by TAT-NSF700 or anti TLR2 antibody. Furthermore, TAT-NSF700 reduced LTA-PGN-induced MLC phosphorylation at low concentrations of 1-10 nM. CONCLUSIONS: TAT-NSF700 decreased Ang-2 release, improved oxygen saturation and pulse distention following pulmonary challenge by inhibiting MLC phosphorylation, an important component of endothelial cell retraction. The data suggest that inhibition of NSF in pneumonia and sepsis may be beneficial to prevent the pulmonary microvascular and hemodynamic instability associated with ARDS. PMID- 27355325 TI - Constrained Allocation Flux Balance Analysis. AB - New experimental results on bacterial growth inspire a novel top-down approach to study cell metabolism, combining mass balance and proteomic constraints to extend and complement Flux Balance Analysis. We introduce here Constrained Allocation Flux Balance Analysis, CAFBA, in which the biosynthetic costs associated to growth are accounted for in an effective way through a single additional genome wide constraint. Its roots lie in the experimentally observed pattern of proteome allocation for metabolic functions, allowing to bridge regulation and metabolism in a transparent way under the principle of growth-rate maximization. We provide a simple method to solve CAFBA efficiently and propose an "ensemble averaging" procedure to account for unknown protein costs. Applying this approach to modeling E. coli metabolism, we find that, as the growth rate increases, CAFBA solutions cross over from respiratory, growth-yield maximizing states (preferred at slow growth) to fermentative states with carbon overflow (preferred at fast growth). In addition, CAFBA allows for quantitatively accurate predictions on the rate of acetate excretion and growth yield based on only 3 parameters determined by empirical growth laws. PMID- 27355326 TI - Identification of Potentially Pathogenic Variants in the Posterior Polymorphous Corneal Dystrophy 1 Locus. AB - Posterior polymorphous corneal dystrophy 1 (PPCD1) is a genetic disorder that affects corneal endothelial cell function and leads to loss of visual acuity. PPCD1 has been linked to a locus on chromosome 20 in multiple families; however, Sanger sequencing of protein-coding genes in the consensus region failed to identify any causative missense mutations. In this study, custom capture probes were utilized for targeted next-generation sequencing of the linked region in a previously reported family with PPCD1. Variants were detected through two bioinformatics pipelines and filtered according to multiple criteria. Additionally, a high-resolution microarray was used to detect copy number variations. No non-synonymous variants in the protein-coding region of annotated genes were identified. However, 12 single nucleotide variants in 10 genes, and 9 indels in 7 genes met the filtering criteria and were considered candidate variants for PPCD1. Eleven single nucleotide variants were confirmed by Sanger sequencing, including 2 synonymous variants and 9 non-coding variants, in 9 genes. One microdeletion was detected in an intron of OVOL2 by microarray but was subsequently not identified by PCR. Using a comprehensive next-generation sequencing approach, a total of 16 genes containing single nucleotide variants or indels that segregated with the affected phenotype in an affected family previously mapped to the PPCD1 locus were identified. Screening of these candidate genes in other families previously mapped to the PPCD1 locus will likely result in the identification of the genetic basis of PPCD1. PMID- 27355327 TI - Mining and Analysis of SNP in Response to Salinity Stress in Upland Cotton (Gossypium hirsutum L.). AB - Salinity stress is a major abiotic factor that affects crop output, and as a pioneer crop in saline and alkaline land, salt tolerance study of cotton is particularly important. In our experiment, four salt-tolerance varieties with different salt tolerance indexes including CRI35 (65.04%), Kanghuanwei164 (56.19%), Zhong9807 (55.20%) and CRI44 (50.50%), as well as four salt-sensitive cotton varieties including Hengmian3 (48.21%), GK50 (40.20%), Xinyan96-48 (34.90%), ZhongS9612 (24.80%) were used as the materials. These materials were divided into salt-tolerant group (ST) and salt-sensitive group (SS). Illumina Cotton SNP 70K Chip was used to detect SNP in different cotton varieties. SNPv (SNP variation of the same seedling pre- and after- salt stress) in different varieties were screened; polymorphic SNP and SNPr (SNP related to salt tolerance) were obtained. Annotation and analysis of these SNPs showed that (1) the induction efficiency of salinity stress on SNPv of cotton materials with different salt tolerance index was different, in which the induction efficiency on salt-sensitive materials was significantly higher than that on salt-tolerant materials. The induction of salt stress on SNPv was obviously biased. (2) SNPv induced by salt stress may be related to the methylation changes under salt stress. (3) SNPr may influence salt tolerance of plants by affecting the expression of salt-tolerance related genes. PMID- 27355328 TI - FABP1 and FABP3 Have High Predictive Values for Renal Replacement Therapy in Patients with Acute Kidney Injury. AB - BACKGROUND/AIMS: Early initiation of renal replacement therapy (RRT) is recommended in order to improve the clinical outcome of patients who develop an acute kidney injury (AKI). However, markers that guide an early RRT initiation do not really exist currently. METHODS: Urine and serum samples were prospectively collected from 120 AKI patients. Depending on the necessity of initiating RRT, patients were divided into 2 different groups: dialysis (n = 52) and non-dialysis (n = 68). RESULTS: Comparative urinary proteomic analyses identified 4 different proteins (fatty acid binding proteins 1 and 3 (FABP1 and FABP3), beta-2 microglobulin (B2M), cystatin-M (CST6)) that discriminate AKI patients with high risk for RRT. Western blot analysis confirmed the proteomics data for FABP1 and FABP3 but not for B2M and CST6. Validation analysis confirmed that the FABP1 and FABP3 fulfilled the requirement of functioning as markers for AKI patients with risk to dialysis (p < 0.001). CONCLUSION: The release of high amounts of FABP1 and FABP3 in urine of AKI patients could serve as a diagnostic/prognosis marker for RRT initiation in these patients. PMID- 27355329 TI - Galectin-1-induced skeletal muscle cell differentiation of mesenchymal stem cells seeded on an acellular dermal matrix improves injured anal sphincter. AB - According to recent studies, mesenchymal stromal cells (MSCs) transplanted via local or tail vein injection can improve healing after anal sphincter injury (ASI) in animal models. However, the transplanted MSCs do not generate skeletal muscle that completely resembles the natural anal sphincter structure. In the present study, we investigated whether bone marrow (BM)-derived MSCs could be induced by Galectin-1 (Gal-1) to differentiate into skeletal muscle and whether the recellularization of an acellular dermal matrix (ADM) with skeletal muscle differentiated MSCs represents a promising approach to restore ASI in a rat model. BM-MSCs subjected to adenovirus-mediated transfection with Gal-1-GFP (Ad GFP-Gal-1) displayed increased Gal-1 and desmin expression and differentiated into skeletal muscle cells. MSCs transfected with Ad-GFP-Gal-1 (MSC-Gal-1) were seeded onto an ADM (ADM-MSC-Gal-1) via co-culture, and fusion was observed using a confocal laser scanning microscope. ADM-MSC-Gal-1, ADM-MSC, ADM-MSC-Ad, ADM, or a saline control was applied to a rat ASI model, and injury healing was evaluated via histological examination 6 weeks following treatment. ADM-MSC-Gal-1 treatment promoted significant healing after ASI and improved external anal sphincter contraction curves compared with the other treatments and also led to substantial skeletal muscle regeneration and neovascularization. Our results indicate that repair using ADMs and differentiated MSCs may improve muscle regeneration and restore ASI. PMID- 27355330 TI - Pathological complete response with anti-PD-1 therapy in a patient with microsatellite instable high, BRAF mutant metastatic colon cancer: a case report and review of literature. AB - IMPORTANCE: Mismatch repair (MMR) and BRAF mutation status are established independent prognostic factors for colorectal cancer (CRC). MMR deficient tumors are considered to have better prognosis whereas BRAF mutation is associated with poor prognosis. Studies evaluating the combined effect of BRAF and MMR status suggest MSI-high and BRAF mutant patients have a poorer prognosis as compared to MSI-high and BRAF wild type patients. Emerging evidence suggests MMR status predicts the immune response to anti-PD-1 therapy in CRC patients; however little is known about combined MMR and BRAF mutation status in this context. Therefore, it is important to identify whether there is a differential response to anti-PD-1 therapy based on BRAF status in the subset of MSI-high CRC patients. OBSERVATIONS: We report the first case of MSI-high, BRAF mutant metastatic CRC that had an excellent response (pathologic complete response) to anti-PD-1 therapy. We take this opportunity to review the similar cases in literature and discuss combined MMR and BRAF status as a potential biomarker for anti-PD-1 therapy. CONCLUSION AND RELEVANCE: The case presented illustrates that anti-PD-1 therapy can be effectively used to treat CRC patients with MSI-high and BRAF mutant status which is usually considered a poor prognostic category as opposed to MSI-high and BRAF wild type tumors. Future studies with anti-PD-1 therapy distinguishing these molecular subgroups will improve our knowledge of whether BRAF status can add to MMR status as a predictive biomarker for anti-PD-1 therapy in patients with metastatic CRC. PMID- 27355331 TI - Therapeutic effects of a novel PIGF-1 derived peptide, ZY-1, on corneal neovascularization in vitro and in vivo. AB - Corneal neovascularization (NV) is one of the major sight-threatening pathological changes caused by corneal diseases. Current therapeutics generate various adverse effects. Small peptides derived from endogenous protein display certain advantages. This study aims to evaluate the anti-angiogenic effect and molecular mechanism of a novel peptide ZY-1, derived from placental growth factor 1 (PlGF-1), on corneal NV by topical administration, and to investigate its safety profile after long-term treatment. CCK-8 assay and tube formation assay were used to evaluate the effect of ZY-1 on human umbilical vein endothelial cells (HUVECs). The anti-angiogenic effect of topical ZY-1 was estimated in a rat model of alkali burn induced corneal NV. The safety profile of topical ZY-1 was analyzed by CCK-8 assay, tear film break-up time (BUT), and histological examination. Firstly, we found that ZY-1 co-localized with membrane vascular epithelial growth factor receptor-1 (VEGFR-1) and effectively inhibited VEGF/PlGF 1 induced proliferation and tube formation of HUVECs. The topical ZY-1 administration efficiently inhibited alkali-burn induced corneal NV, while it did not show any significant effect on human corneal epithelial cell (HCEC) proliferation, as well as the functionality and morphology of cornea and conjunctiva. Our findings suggested that topical administration of ZY-1 could effectively and safely inhibit corneal NV partially through competing for VEGFR-1 binding, and it would be a promising alternative for ocular topical anti angiogenic therapy. PMID- 27355332 TI - Melatonin based therapies for delirium and dementia. AB - Melatonin levels have been shown to decline with aging. Melatonin and its analogs in addition to their effect on sleep promotion, has been shown to have multiple pleiotropic effects. It can also help with neuroprotection through different mechanisms. Evidence in animal and human studies suggests that low levels of melatonin have been linked to delirium, mild cognitive impairment, dementia, and with certain behavioral problems. Recent clinical trials have showed that both melatonin and its analogs may be useful in the prevention, treatment of delirium, and the management of dementia. These medications seem to have the advantage of less side effects and better safety profile when compared to antipsychotics and sedatives like benzodiazepines. These medications are available over the counter in North America, Europe, and Asia, and some of these medications are approved by FDA. This manuscript will discuss the promising role of these melatonergic medications alone or in combination with other medications for the management of Geriatric Psychiatric diseases like delirium and dementia. PMID- 27355333 TI - Targeting isocitrate dehydrogenase (IDH) in cancer. AB - Isocitrate dehydrogenase (IDH) is an essential enzyme for cellular respiration in the tricarboxylic acid (TCA) cycle. Recurrent mutations in IDH1 or IDH2 are prevalent in several cancers including glioma, acute myeloid leukemia (AML), cholangiocarcinoma and chondrosarcoma. The mutated IDH1 and IDH2 proteins have a gain-of-function, neomorphic activity, catalyzing the reduction of alpha ketoglutarate (alpha-KG) to 2-hydroxyglutarate (2-HG) by NADPH. Cancer-associated IDH mutations block normal cellular differentiation and promote tumorigenesis via the abnormal production of the oncometabolite 2-HG. High levels of 2-HG have been shown to inhibit alpha-KG dependent dioxygenases, including histone and deoxyribonucleic acid (DNA) demethylases, which play a key role in regulating the epigenetic state of cells. Current targeted inhibitors of IDH1 (AG120, IDH305), IDH2 (AG221), and pan-IDH1/2 (AG881) selectively inhibit mutant IDH protein and induce cell differentiation in in vitro and in vivo models. Preliminary results from phase I clinical trials with IDH inhibitors in patients with advanced hematologic malignancies have demonstrated an objective response rate ranging from 31% to 40% with durable responses (>1 year) observed. Furthermore, the IDH inhibitors have demonstrated early signals of activity in solid tumors with IDH mutations, including cholangiocarcinomas and low grade gliomas. PMID- 27355334 TI - New concepts in the treatment strategy of neuroendocrine tumors: the role of biotherapy. AB - Neuroendocrine tumors (NETs) comprise a wide range of neoplasms with diverse biological behaviors, often secreting excessive amounts of endocrine-active substances causing hormone syndromes. They are classified according to the location of the primary site and the level of histological differentiation, which has prognostic as well as therapeutic implications. Biotherapy had traditionally a significant role in the treatment of these tumors, when not amenable to surgery or local treatments. Control of carcinoid syndrome with somatostatin analogs (SSAs) significantly contributed to the improvement of the quality of life. Also, interferon has long been administered, but data were based on small studies. In contrast, PROMID and CLARINET randomized phase III trials provided the first strong evidence of significant improvement in progression-free survival in patients with gastroenteropancreatic (GEP)-NETs with octreotide and lanreotide, respectively, validating somatostatin receptors as important targets. Clinical trials testing the role of these SSAs in other primaries, e.g., lung carcinoids, as well as the efficacy of newer analogs are underway. PMID- 27355335 TI - Novel therapeutic approaches and mechanisms in neuroendocrine tumors: the role of targeted agents. AB - Low-intermediate grade neuroendocrine tumors (NETs) are usually slow-growing cancers with a clinical course spanning few to several years managed with active surveillance, locoregional treatments, or somatostain analogs. At some point in their natural history, they develop resistance to these treatments and become more aggressive. Chemotherapy offers only limited therapeutic benefit and any evidence is based on small trials or retrospective studies. The significant progress in molecular biology shed light on the significant role of PI3K/Akt/mTOR pathway and angiogenesis in NETs, while the success of everolimus and sunitinib in landmark clinical trials opened new avenues in the discovery of effective treatments. Ongoing and planned pivotal studies testing newer agents targeting other pathways are underway. In addition to providing better treatment options, these drugs also broadened our understanding of the biology of these tumors. Biomarkers are eagerly needed with the scope of personalizing future treatment. PMID- 27355336 TI - Engineering tolerance using biomaterials to target and control antigen presenting cells. AB - Autoimmune diseases occur when cells of the adaptive immune system incorrectly recognize and attack "self" tissues. Importantly, the proliferation and differentiation of these cells is triggered and controlled by interactions with antigen presenting cells (APCs), such as dendritic cells. Thus, modulating the signals transduced by APCs (e.g., cytokines, costimulatory surface proteins) has emerged as a promising strategy to promote tolerance for diseases such as multiple sclerosis, type 1 diabetes, and lupus. However, many approaches have been hindered by non-specific activity of immunosuppressive or immunoregulatory cues, following systemic administration of soluble factors via traditional injections routes (e.g., subcutaneous, intravenous). Biomaterials offer a unique opportunity to control the delivery of tolerogenic signals in vivo via properties such as controlled particle size, tunable release kinetics, and co-delivery of multiple classes of cargo. In this review, we highlight recent reports that exploit these properties of biomaterials to target APCs and promote tolerance via three strategies, i) passive or active targeting of particulate carriers to APCs, ii) biomaterial-mediated control over antigen localization and processing, and iii) targeted delivery of encapsulated or adsorbed immunomodulatory signals. These reports represent exciting advances toward the goal of more effective therapies for autoimmune diseases, without the broad suppressive effects associated with current clinically-approved therapies. PMID- 27355337 TI - Sex steroid induced apoptosis as a rational strategy to treat anti-hormone resistant breast and prostate cancer. AB - The combined incidence and the extended disease course of breast and prostate cancer is a major challenge for health care systems. The solution for society requires an economically viable treatment strategy to maintain individuals disease free and productive, so as to avoid the fracture of the family unit. Forty years ago, translational research using the antiestrogen tamoxifen was targeted to estrogen receptor (ER) positive micrometastatic tumor cells and established the long-term antihormone adjuvant treatment strategy used universally today. The antihormone strategy was the accepted structure of cancer biology. Sex steroid deprivation therapy remains the orthodox strategy for the treatment of both breast and prostate cancer. Despite major initial therapeutic success, the strategies of long term anti-hormone therapies with either tamoxifen or aromatase inhibitors (AI) or antiandrogens or abiraterone for breast and prostate cancer, respectively, eventually lead to a significant proportion of anti-hormone resistant or stimulated tumor growth. Remarkably, a general principle of anti-hormone resistance has emerged for both breast and prostate cancer based primarily on clinical and supportive laboratory data. Paradoxically, anti-hormone resistant cell populations emerge and grow but are vulnerable to the cytotoxicity of estrogen or androgen-induced apoptosis for both breast and prostate cancer, respectively. These consistent anticancer actions of sex steroids appear to recapitulate the more complex mechanism of bone remodeling in elderly men and women during sex steroid deprivation. Estrogen is the key hormone in both sexes because in men androgen is first converted to estrogen. Estrogen regulates and triggers apoptosis in osteoclasts that develop during estrogen deprivation and destroy bone to cause osteoporosis. Sex steroid deprived breast and prostate cancer has recruited a streamlined natural apoptotic program from the human genome, but this is suppressed in the majority of sex steroid deprived tumors. Targeted strategies to neutralize cell survival pathways are now required to amplify and enhance sex steroid induced apoptosis. Successful blockade of the critical pathways for cell survival will introduce an inexpensive targeted therapy to maintain breast and prostate cancer patients indefinitely. Rotating anti-hormonal and sex steroid targeted cocktails could maintain patients at a microscopic tumor burden to enhance the quality of life, enhance survival, and maintain the family as a self-supporting and economically productive unit within society. PMID- 27355338 TI - Prevention and Periodontal Treatment in Down Syndrome Patients: A Systematic Review. AB - The aim of this systematic literature review was to evaluate which type of periodontal preventive and therapeutic approaches presents superior outcomes in patients with Down syndrome (DS). Studies reporting different methods of periodontal care from DS patients were considered eligible. Included clinical studies should indicate at least two periodontal parameters in different periods of assessment. Screening of the articles, data extraction and quality assessment were conducted independently and in duplicate. Electronic search according to the PICO search, with both Key-words and MESH terms were conducted in MEDLINE, EMBASE and CENTRAL databases until March 2016. Manual search was conducted in four journals, namely Journal of Periodontology, Journal of Clinical Periodontology, Journal of Periodontal Research and Special Care in Dentistry and their electronic databases were searched. Electronic and manual search resulted in 763 papers, and of them 744 were excluded after title/abstract assessment. The full text of 19 potentially eligible publications was screened and 9 studies met inclusion criteria. The results demonstrated the importance to introduce youngest DS patients in preventive programs, as well as participation of parents, caregivers or institutional attendants in supervising/performing oral hygiene. In studies with higher frequency of attendance, all age groups presented superior preventive and therapeutic results, irrespective of the therapeutic approach used (surgical/nonsurgical/periodontal care program). The important factors for reducing periodontal parameters were the frequency of the appointments and association with chlorhexidine/plaque disclosing agents as adjuvant treatment. This systematic review demonstrated that early introduction in periodontal care, participation of parents/caregivers/institutional attendants, frequency of attendance and association with chemical adjuvants (independently of the periodontal treatment adopted) seems to improve periodontal outcomes in preventive and periodontal treatment of DS patients. Registration number (Prospero): CRD42016038433. PMID- 27355339 TI - Characteristics of Hyperautofluorescent Choroidal Vessels within the Macular Atrophic Area Using Spectral-Domain Optical Coherence Tomography. PMID- 27355340 TI - Proximal Soil Sensing - A Contribution for Species Habitat Distribution Modelling of Earthworms in Agricultural Soils? AB - BACKGROUND: Earthworms are important for maintaining soil ecosystem functioning and serve as indicators of soil fertility. However, detection of earthworms is time-consuming, which hinders the assessment of earthworm abundances with high sampling density over entire fields. Recent developments of mobile terrestrial sensor platforms for proximal soil sensing (PSS) provided new tools for collecting dense spatial information of soils using various sensing principles. Yet, the potential of PSS for assessing earthworm habitats is largely unexplored. This study investigates whether PSS data contribute to the spatial prediction of earthworm abundances in species distribution models of agricultural soils. METHODOLOGY/PRINCIPAL FINDINGS: Proximal soil sensing data, e.g., soil electrical conductivity (EC), pH, and near infrared absorbance (NIR), were collected in real time in a field with two management strategies (reduced tillage / conventional tillage) and sandy to loam soils. PSS was related to observations from a long term (11 years) earthworm observation study conducted at 42 plots. Earthworms were sampled from 0.5 x 0.5 x 0.2 m3 soil blocks and identified to species level. Sensor data were highly correlated with earthworm abundances observed in reduced tillage but less correlated with earthworm abundances observed in conventional tillage. This may indicate that management influences the sensor-earthworm relationship. Generalized additive models and state-space models showed that modelling based on data fusion from EC, pH, and NIR sensors produced better results than modelling without sensor data or data from just a single sensor. Regarding the individual earthworm species, particular sensor combinations were more appropriate than others due to the different habitat requirements of the earthworms. Earthworm species with soil-specific habitat preferences were spatially predicted with higher accuracy by PSS than more ubiquitous species. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that PSS contributes to the spatial modelling of earthworm abundances at field scale and that it will support species distribution modelling in the attempt to understand the soil-earthworm relationships in agroecosystems. PMID- 27355341 TI - Formation of nanowires via single particle-triggered linear polymerization of solid-state aromatic molecules. AB - Nanowires occupy a prestigious place in nanoelectronics, nanomechanics, and biomimetics. Although there are notable methods to grow nanowires via self assembly, there is a key drawback in the need to find out the specific conditions appropriate for each system. In this sense, universal techniques to fabricate such nanowires from various organic materials have been sought for the continued progress of the related research field. Here we report one of the promising and facile methodologies to quantitatively produce nanowires with controlled geometrical parameters. In this method, referred to as "Single Particle-Triggered Linear Polymerization (STLiP)", organic thin films on a supporting substrate were irradiated with high-energy charged particles, accelerated by particle accelerators. Each particle penetrates from the top of the films to the substrate while gradually releasing kinetic energy along its trajectory (ion track), generating reactive intermediates such as radical species that eventually induce propagation reactions. The resulting polymerized products were integrated into nanowires with uniform diameter and length that can be isolated via development with appropriate organic solvents. Considering the widely applicable nature of STLiP to organic materials, the present technique opens a new door for access to a number of functional nanowires and their assembly. PMID- 27355342 TI - Synthesis of Fasicularin. AB - The synthesis of a tricyclic marine alkaloid, fasicularin, was accomplished. Stereoselective synthesis of the aza-spirocyclic BC-ring precursor and ensuing construction of the A-ring with stereocontrolled installation of the C2 hexyl group feature prominently in the synthesis. PMID- 27355343 TI - Watching Subtitled Films Can Help Learning Foreign Languages. AB - Watching English-spoken films with subtitles is becoming increasingly popular throughout the world. One reason for this trend is the assumption that perceptual learning of the sounds of a foreign language, English, will improve perception skills in non-English speakers. Yet, solid proof for this is scarce. In order to test the potential learning effects derived from watching subtitled media, a group of intermediate Spanish students of English as a foreign language watched a 1h-long episode of a TV drama in its original English version, with English, Spanish or no subtitles overlaid. Before and after the viewing, participants took a listening and vocabulary test to evaluate their speech perception and vocabulary acquisition in English, plus a final plot comprehension test. The results of the listening skills tests revealed that after watching the English subtitled version, participants improved these skills significantly more than after watching the Spanish subtitled or no-subtitles versions. The vocabulary test showed no reliable differences between subtitled conditions. Finally, as one could expect, plot comprehension was best under native, Spanish subtitles. These learning effects with just 1 hour exposure might have major implications with longer exposure times. PMID- 27355344 TI - Correction: BMP4 Signaling Is Able to Induce an Epithelial-Mesenchymal Transition Like Phenotype in Barrett's Esophagus and Esophageal Adenocarcinoma through Induction of SNAIL2. AB - [This corrects the article DOI: 10.1371/journal.pone.0155754.]. PMID- 27355345 TI - Methylation Landscape of Human Breast Cancer Cells in Response to Dietary Compound Resveratrol. AB - Aberrant DNA methylation is a frequent epigenetic alteration in cancer cells that has emerged as a pivotal mechanism for tumorigenesis. Accordingly, novel therapies targeting the epigenome are being explored with the aim to restore normal DNA methylation patterns on oncogenes and tumor suppressor genes. A limited number of studies indicate that dietary compound resveratrol modulates DNA methylation of several cancer-related genes; however a complete view of changes in methylome by resveratrol has not been reported yet. In this study we performed a genome-wide survey of DNA methylation signatures in triple negative breast cancer cells exposed to resveratrol. Our data showed that resveratrol treatment for 24 h and 48 h decreased gene promoter hypermethylation and increased DNA hypomethylation. Of 2476 hypermethylated genes in control cells, 1,459 and 1,547 were differentially hypomethylated after 24 h and 48 h, respectively. Remarkably, resveratrol did not induce widespread non-specific DNA hyper- or hypomethylation as changes in methylation were found in only 12.5% of 27,728 CpG loci. Moreover, resveratrol restores the hypomethylated and hypermethylated status of key tumor suppressor genes and oncogenes, respectively. Importantly, the integrative analysis of methylome and transcriptome profiles in response to resveratrol showed that methylation alterations were concordant with changes in mRNA expression. Our findings reveal for the first time the impact of resveratrol on the methylome of breast cancer cells and identify novel potential targets for epigenetic therapy. We propose that resveratrol may be considered as a dietary epidrug as it may exert its anti-tumor activities by modifying the methylation status of cancer -related genes which deserves further in vivo characterization. PMID- 27355346 TI - Predicting ADHD by Assessment of Rutter's Indicators of Adversity in Infancy. AB - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with early onset. ADHD is associated with significant morbidity and mortality, partly due to delayed diagnosis. Identification of children at high risk for developing ADHD could lead to earlier diagnosis and potentially change the negative trajectory of the illness for the better. Since early psychosocial adversity is considered to be a likely etiological risk factor for ADHD, markers of this construct may be useful for early identification of children at high risk. Therefore, we sought to investigate whether Rutter's indicators of adversity (low social class, severe marital discord, large family size, paternal criminality, maternal mental disorder, and placement in out-of home care) assessed in infancy could serve as early predictors for the development of ADHD. METHODS AND FINDINGS: Using data from the Danish nationwide population-based registers, we established a cohort consisting of all 994,407 children born in Denmark between January 1st 1993 and December 31st 2011 and extracted dichotomous values for the six Rutter's indicators of adversity at age 0-12 months (infancy) for each cohort member. The cohort members were followed from their second birthday and the association between the sum of Rutter's indicators of adversity (RIA-score) in infancy and subsequent development of ADHD was estimated by means of Cox regression. Also, the number needed to screen (NNS) to detect one case of ADHD based on the RIA-scores in infancy was calculated. During follow-up (9.6 million person-years), 15,857 males and 5,663 females from the cohort developed ADHD. For both males and females, there was a marked dose response relationship between RIA-scores assessed in infancy and the risk for developing ADHD. The hazard ratios for ADHD were 11.0 (95%CI: 8.2-14.7) and 11.4 (95%CI: 7.1-18.3) respectively, for males and females with RIA-scores of 5-6, compared to males and females with RIA-scores of 0. Among males with RIA-scores of 5-6, 37.6% (95%CI: 27.0-50.7) had been diagnosed with ADHD prior to the age of 20, corresponding to a NNS of 3.0 (95%CI: 2.2-4.0). CONCLUSIONS: Rutter's indicators of adversity assessed in infancy strongly predicted ADHD. This knowledge may be important for early identification of ADHD. PMID- 27355348 TI - Variation in the radon concentrations and outdoor gamma radiation levels in relation to different geological formations in the thermal regions of Bursa, Turkey. AB - Spring waters used as spas and their region may contain significant amounts of natural radionuclides. The main sources of exposure are the inhalation of radon and its decay products released from the water and soil and terrestrial gamma radiation. In order to evaluate the potential risk of thermal regions in Bursa, located in the impact area of the NAF (North Anatolian Fault), radon and thoron concentrations in soil gas, radon concentrations in thermal waters and outdoor gamma radiation levels were measured in thermal regions that have different geological formations. The radon and thoron concentrations in soil-gas were found to vary from 2272 +/- 121 to 245196 +/- 3455 Bq m-3 and from 999 +/- 218 to 178 848 +/- 17 742 Bq m-3, respectively. The radon concentrations in thermal waters ranged from 0.99 +/- 0.21 to 226.74 +/- 2.51 Bq l-1 in the rainy season and from 0.26 +/- 0.10 to 178.03 +/- 12.86 Bq l-1 in the dry season. The measured outdoor gamma radiation levels varied from 38 to 180 nGy h-1. The gamma dose rates were found to be strong positively correlating with the radon and thoron concentrations in soil-gas. The radon and outdoor gamma radiation levels were observed to be a function of the geological formations of the area. PMID- 27355347 TI - Rare Variants Association Analysis in Large-Scale Sequencing Studies at the Single Locus Level. AB - Genetic association analyses of rare variants in next-generation sequencing (NGS) studies are fundamentally challenging due to the presence of a very large number of candidate variants at extremely low minor allele frequencies. Recent developments often focus on pooling multiple variants to provide association analysis at the gene instead of the locus level. Nonetheless, pinpointing individual variants is a critical goal for genomic researches as such information can facilitate the precise delineation of molecular mechanisms and functions of genetic factors on diseases. Due to the extreme rarity of mutations and high dimensionality, significances of causal variants cannot easily stand out from those of noncausal ones. Consequently, standard false-positive control procedures, such as the Bonferroni and false discovery rate (FDR), are often impractical to apply, as a majority of the causal variants can only be identified along with a few but unknown number of noncausal variants. To provide informative analysis of individual variants in large-scale sequencing studies, we propose the Adaptive False-Negative Control (AFNC) procedure that can include a large proportion of causal variants with high confidence by introducing a novel statistical inquiry to determine those variants that can be confidently dispatched as noncausal. The AFNC provides a general framework that can accommodate for a variety of models and significance tests. The procedure is computationally efficient and can adapt to the underlying proportion of causal variants and quality of significance rankings. Extensive simulation studies across a plethora of scenarios demonstrate that the AFNC is advantageous for identifying individual rare variants, whereas the Bonferroni and FDR are exceedingly over-conservative for rare variants association studies. In the analyses of the CoLaus dataset, AFNC has identified individual variants most responsible for gene-level significances. Moreover, single-variant results using the AFNC have been successfully applied to infer related genes with annotation information. PMID- 27355349 TI - HMGB1-RAGE Axis Makes No Contribution to Cardiac Remodeling Induced by Pressure Overload. AB - High-mobility group box1 (HMGB1) exerts effects on inflammation by binding to receptor for advanced glycation end products (RAGE) or Toll-like receptor 4. Considering that inflammation is involved in pressure overload-induced cardiac hypertrophy, we herein attempted to investigate whether HMGB1 plays a role in myocardial hypertrophy in RAGE knockout mice as well as in the growth and apoptosis of cardiomyocytes. The myocardial expression of RAGE was not significantly changed while TLR4 mRNA was upregulated in response to transverse aortic constriction (TAC) for 1 week. The myocardial expression of HMGB1 protein was markedly increased in TAC group when compared to the sham group. Heart weight to body weight ratio (HW/BW) and lung weight to body weight ratio (LW/BW) were evaluated in RAGE knockout (KO) and wild-type (WT) mice 1 week after TAC. Significant larger HW/BW and LW/BW ratios were found in TAC groups than the corresponding sham groups, but no significant difference was found between KO and WT TAC mice. Similar results were also found when TAC duration was extended to 4 weeks. Cultured neonatal rat cardiomyocytes were treated with different concentrations of recombinant HMGB1, then cell viability was determined using MTT and CCK8 assays and cell apoptosis was determined by Hoechst staining and TUNEL assay. The results came out that HMGB1 exerted no influence on viability or apoptosis of cardiomyocytes. Besides, the protein expression levels of Bax and Bcl2 in response to different concentrations of HMGB1 were similar. These findings indicate that HMGB1 neither exerts influence on cardiac remodeling by binding to RAGE nor induces apoptosis of cardiomyocytes under physiological condition. PMID- 27355350 TI - Regional Volume Decreases in the Brain of Pax6 Heterozygous Mutant Rats: MRI Deformation-Based Morphometry. AB - Pax6 is a transcription factor that pleiotropically regulates various developmental processes in the central nervous system. In a previous study, we revealed that Pax6 heterozygous mutant (rSey2/+) adult rats exhibit abnormalities in social interaction. However, the brain malformations underlying the behavioral abnormality are unknown. To elucidate the brain malformations in rSey2/+ rats, we morphometrically analyzed brains of rSey2/+ and wild type rats using small-animal magnetic resonance imaging (MRI). Sixty 10-week-old rats underwent brain MRI (29 rSey2/+ rats and 31 wild type rats). SPM8 software was used for image preprocessing and statistical image analysis. Normalized maps of the Jacobian determinant, a parameter for the expansion and/or contraction of brain regions, were obtained for each rat. rSey2/+ rats showed significant volume decreases in various brain regions including the neocortex, corpus callosum, olfactory structures, hippocampal formation, diencephalon, and midbrain compared to wild type rats. Among brain regions, the anterior commissure showed significant interaction between genotype and sex, indicating the effect of genotype difference on the anterior commissure volume was more robust in females than in males. The rSey2/+ rats exhibited decreased volume in various gray and white matter regions of the brain, which may contribute to manifestation of abnormal social behaviors. PMID- 27355351 TI - CT Scan of Thirteen Natural Mummies Dating Back to the XVI-XVIII Centuries: An Emerging Tool to Investigate Living Conditions and Diseases in History. AB - OBJECTIVES: To correlate the radiologic findings detected with computed tomography scan with anthropological data in 13 naturally mummified bodies discovered during works of recovery of an ancient church in a crypt in Roccapelago, in the Italian Apennines. METHODS: From a group of about sixty not intentionally mummified bodies, thirteen were selected to be investigated with volumetric computed tomography (CT). Once CT scan was performed, axial images were processed to gather MPR and Volume Rendering reconstructions. Elaborations of these images provided anthropometric measurements and a non-invasive analysis of the residual anatomical structures. For each body the grade of preservation and the eventual pathological changes were recorded. Furthermore, in order to identify nutritional and occupational markers, radiologic signs of bone tropism and degenerative changes were analysed and graded. RESULTS: Mummies included seven females and six males, with an estimated age ranging from 20 to 60 years. The first relevant finding identified was a general low grade of preservation, due to the lack of anatomic tissues different from bones, tendons and dehydrated skin. The low grade of preservation was related to the natural process of mummification. Analysing bone degenerative changes on CT scan, the majority of the bodies had significant occupational markers consisting of arthritis in the spine, lower limbs and shoulders even in young age. Few were the pathological findings identified. Among these, the most relevant included a severe bilateral congenital hip dysplasia and a wide osteolytic lesion involving left orbit and petrous bone that was likely the cause of death. CONCLUSIONS: Although the low grade of preservation of these mummies, the multidisciplinary approach of anthropologists and radiologists allowed several important advances in knowledge for the epidemiology of Roccapelago. First of all, a profile of living conditions was delineated. It included occupational and nutritional conditions. Moreover, identification of some causes of death and, most importantly the definition of general living conditions. PMID- 27355352 TI - Transcriptome Profiling Reveals the Antitumor Mechanism of Polysaccharide from Marine Algae Gracilariopsis lemaneiformis. AB - Seaweed is one of the important biomass producers and possesses active metabolites with potential therapeutic effects against tumors. The red alga Gracilariopsis lemaneiformis (Gp. lemaneiformis) possesses antitumor activity, and the polysaccharide of Gp. lemaneiformis (PGL) has been demonstrated to be an ingredient with marked anticancer activity. However, the anticancer mechanism of PGL remains to be elucidated. In this study, we analyzed the inhibitory effect of PGL on the cell growth of 3 human cancer cell lines and found that PGL inhibited cell proliferation, reduced cell viability, and altered cell morphology in a time and concentration-dependent manner. Our transcriptome analysis indicates that PGL can regulate the expression of 758 genes, which are involved in apoptosis, the cell cycle, nuclear division, and cell death. Furthermore, we demonstrated that PGL induced apoptosis and cell cycle arrest and modulated the expression of related genes in the A549 cell line. Our work provides a framework to understand the effects of PGL on cancer cells, and can serve as a resource for delineating the antitumor mechanisms of Gp. lemaneiformis. PMID- 27355353 TI - Calcium Prerinse before Fluoride Rinse Reduces Enamel Demineralization: An in situ Caries Study. AB - A calcium (Ca) prerinse before a fluoride (F) rinse has been shown to increase oral F levels. We tested the anticaries effect of this combination in a dose response in situ caries model. In a double-blind, crossover experiment, 10 volunteers carried enamel slabs in palatal appliances for 14 days, during which they rinsed twice/day with one of four rinse combinations: (1) a placebo prerinse (150 mM sodium lactate) followed by a distilled water rinse (negative control); (2) a placebo prerinse followed by a 250 ppm F rinse; (3) a placebo prerinse followed by a 1,000 ppm F rinse, or (4) a Ca prerinse (150 mM Ca, as calcium lactate) followed by a 250 ppm F rinse. Sucrose solution was dripped onto the slabs 8*/day to simulate a high cariogenic challenge. The percent surface hardness loss (%SHL) was significantly lower in the Ca prerinse used with the 250 ppm F rinse group (%SHL = 38.0 +/- 21.0) when compared with the F rinse alone (%SHL = 59.5 +/- 24.1) and similar to the 1,000 ppm F rinse group (%SHL = 42.0 +/ 18.3). Compared with the 250 ppm F rinse, the Ca prerinse increased biofilm fluid F only twice (nonsignificant). However, it greatly increased F in biofilm solids (~22*). The Ca prerinse had little effect on loosely or firmly bound enamel F. The results showed an increased level of protection against demineralization by the use of a Ca prerinse, which seems to be caused by the enhancement of F concentration in the biofilm. PMID- 27355354 TI - Do Wild Great Tits Avoid Exposure to Light at Night? AB - Studies of wild populations have provided important insights into the effects of artificial light at night on organisms, populations and ecosystems. However, in most studies the exact amount of light at night individuals are exposed to remains unknown. Individuals can potentially control their nighttime light exposure by seeking dark spots within illuminated areas. This uncertainty makes it difficult to attribute effects to a direct effect of light at night, or to indirect effects, e.g., via an effect of light at night on food availability. In this study, we aim to quantify the nocturnal light exposure of wild birds in a previously dark forest-edge habitat, experimentally illuminated with three different colors of street lighting, in comparison to a dark control. During two consecutive breeding seasons, we deployed male great tits (Parus major) with a light logger measuring light intensity every five minutes over a 24h period. We found that three males from pairs breeding in brightly illuminated nest boxes close to green and red lamp posts, were not exposed to more artificial light at night than males from pairs breeding further away. This suggests, based on our limited sample size, that these males could have been avoiding light at night by choosing a roosting place with a reduced light intensity. Therefore, effects of light at night previously reported for this species in our experimental set-up might be indirect. In contrast to urban areas where light is omnipresent, bird species in non-urban areas may evade exposure to nocturnal artificial light, thereby avoiding direct consequences of light at night. PMID- 27355355 TI - The Path towards Endangered Species: Prehistoric Fisheries in Southeastern Brazil. AB - Brazilian shellmounds are archaeological sites with a high concentration of marine faunal remains. There are more than 2000 sites along the coast of Brazil that range in age from 8,720 to 985 cal BP. Here, we studied the ichthyoarchaeological remains (i.e., cranial/postcranial bones, otoliths, and teeth, among others) at 13 shellmounds on the southern coast of the state of Rio de Janeiro, which are located in coastal landscapes, including a sandy plain with coastal lagoons, rocky islands, islets and rocky bays. We identified patterns of similarity between shellmounds based on fish diversity, the ages of the assemblages, littoral geomorphology and prehistoric fisheries. Our new radiocarbon dating, based on otolith samples, was used for fishery characterization over time. A taxonomical study of the ichthyoarchaeological remains includes a diversity of 97 marine species, representing 37% of all modern species (i.e., 265 spp.) that have been documented along the coast of Rio de Janeiro state. This high fish diversity recovered from the shellmounds is clear evidence of well-developed prehistoric fishery activity that targeted sharks, rays and finfishes in a productive area influenced by coastal marine upwelling. The presence of adult and neonate shark, especially oceanic species, is here interpreted as evidence of prehistoric fisheries capacity for exploitation and possibly overexploitation in nursery areas. Various tools and strategies were used to capture finfish in seasonal fisheries, over rocky reef bottoms and in sandy littoral environments. Massive catches of whitemouth croaker, main target dermersal species of South Atlantic coast, show evidence of a reduction in body size of approximately 28% compared with modern fisheries. Fishery activity involving vulnerable species, especially in nursery areas, could mark the beginning of fish depletion along the southeastern Brazilian coast and the collapse of natural fish populations. PMID- 27355356 TI - Chemosensitivity, Cardiovascular Risk, and the Ventilatory Response to Exercise in COPD. AB - COPD is associated with elevated cardiovascular risk and a potentiated ventilatory response to exercise. Enhanced carotid chemoreceptor (CC) activity/sensitivity is present in other clinical conditions, has been shown to contribute to sympathetic vasoconstrictor outflow, and is predictive of mortality. CC activity/sensitivity, and the resulting functional significance, has not been well examined in COPD. We hypothesized that CC activity/sensitivity would be elevated in COPD, and related to increased pulse wave velocity (a marker of CV risk) and the ventilatory response to exercise. METHODS: 30 COPD patients and 10 healthy age-matched controls were examined. Participants performed baseline cardiopulmonary exercise and pulmonary function testing. CC activity was later evaluated by the drop in ventilation with breathing 100% O2, and CC sensitivity was then assessed by the ventilatory response to hypoxia (DeltaVE/DeltaSpO2). Peripheral arterial stiffness was subsequently evaluated by measurement of pulse wave velocity (PWV) using applanation tonometry while the subjects were breathing room air, and then following chemoreceptor inhibition by breathing 100% O2 for 2 minutes. RESULTS: CC activity, CC sensitivity, PWV and the ventilatory response to exercise were all increased in COPD relative to controls. CC sensitivity was related to PWV; however, neither CC activity nor CC sensitivity was related to the ventilatory response to exercise in COPD. CC inhibition by breathing 100% O2 normalized PWV in COPD, while no effect was observed in controls. CONCLUSION: CC activity and sensitivity are elevated in COPD, and appear related to cardiovascular risk; however, CC activity/sensitivity does not contribute to the potentiated ventilatory response to exercise. PMID- 27355358 TI - Evaluation of Transbronchial Lung Cryobiopsy Size and Freezing Time: A Prognostic Animal Study. AB - BACKGROUND: Transbronchial lung biopsy using a cryoprobe is a novel way of sampling lung parenchyma. Correlation of freezing time with biopsy size and complications has not been evaluated in vivo. OBJECTIVES: The primary aim of the study is to evaluate the correlation between transbronchial cryobiopsy freezing time and size. The secondary aims are to evaluate histological quality of the biopsy and evaluate procedure-associated complications. METHODS: Transbronchial lung cryobiopsies were obtained from two anaesthetised sheep using a 1.9-mm cryoprobe inserted into a flexible bronchoscope under fluoroscopic guidance. Freezing times ranged from 1 to 6 s (n = 49). The cryobiopsies were evaluated histologically with respect to their size and quality. Complications of bleeding and pneumothorax were recorded. RESULTS: The mean cross-sectional area of the cryobiopsy ranged from 4.7 +/- 2.1 to 15.7 +/- 15.3 mm2. There was a significant positive correlation between increasing freezing time and cryobiopsy cross sectional area (p = 0.028). All biopsies contained lung tissue with preserved parenchyma. Crush and freeze artefacts were not observed and tissue architecture was intact in all specimens. Small blood vessels and terminal bronchioles were observed in 88% of specimens. All cryobiopsies caused nil or mild haemorrhage with the exception of only 1 episode of severe haemorrhage at 6 s freezing time. Pneumothoraces occurred at 2, 5 and 6 s freezing time and required chest tube insertion. The most significant haemorrhage and pneumothoraces occurred at 5 and 6 s. Our results suggest an initial freezing time of 3 s can provide the maximal biopsy size while minimising major complications. CONCLUSION: The optimal transbronchial cryobiopsy freezing time is initially 3 s. This time is associated with minimal complications and large artefact-free biopsies. PMID- 27355359 TI - Wearable Biosensors Studied for Clinical Monitoring and Treatment. PMID- 27355357 TI - Cancers Screening in an Asymptomatic Population by Using Multiple Tumour Markers. AB - BACKGROUND: Analytic measurement of serum tumour markers is one of commonly used methods for cancer risk management in certain areas of the world (e.g. Taiwan). Recently, cancer screening based on multiple serum tumour markers has been frequently discussed. However, the risk-benefit outcomes appear to be unfavourable for patients because of the low sensitivity and specificity. In this study, cancer screening models based on multiple serum tumour markers were designed using machine learning methods, namely support vector machine (SVM), k nearest neighbour (KNN), and logistic regression, to improve the screening performance for multiple cancers in a large asymptomatic population. METHODS: AFP, CEA, CA19-9, CYFRA21-1, and SCC were determined for 20 696 eligible individuals. PSA was measured in men and CA15-3 and CA125 in women. A variable selection process was applied to select robust variables from these serum tumour markers to design cancer detection models. The sensitivity, specificity, positive predictive value (PPV), negative predictive value, area under the curve, and Youden index of the models based on single tumour markers, combined test, and machine learning methods were compared. Moreover, relative risk reduction, absolute risk reduction (ARR), and absolute risk increase (ARI) were evaluated. RESULTS: To design cancer detection models using machine learning methods, CYFRA21-1 and SCC were selected for women, and all tumour markers were selected for men. SVM and KNN models significantly outperformed the single tumour markers and the combined test for men. All 3 studied machine learning methods outperformed single tumour markers and the combined test for women. For either men or women, the ARRs were between 0.003-0.008; the ARIs were between 0.119 0.306. CONCLUSION: Machine learning methods outperformed the combined test in analysing multiple tumour markers for cancer detection. However, cancer screening based solely on the application of multiple tumour markers remains unfavourable because of the inadequate PPV, ARR, and ARI, even when machine learning methods were incorporated into the analysis. PMID- 27355360 TI - Generation of Anti-Boa Immunoglobulin Antibodies for Serodiagnostic Applications, and Their Use to Detect Anti-Reptarenavirus Antibodies in Boa Constrictor. AB - Immunoglobulins (Igs), the key effectors of the adaptive immune system, mediate the specific recognition of foreign structures, i.e. antigens. In mammals, IgM production commonly precedes the production of IgG in the response to an infection. The reptilian counterpart of IgG is IgY, but the exact kinetics of the reptilian immune response are less well known. Boid inclusion body disease (BIBD), an often fatal disease of captive boas and pythons has been linked to reptarenavirus infection, and BIBD is believed to be immunosuppressive. However, so far, the study of the serological response towards reptarenaviruses in BIBD has been hampered by the lack of reagents. Thus we set up a purification protocol for boa constrictor IgY and IgM, which should also be applicable for other snake species. We used centrifugal filter units, poly ethylene glycol precipitation and gel permeation chromatography to purify and separate the IgM and IgY fractions from boa constrictor serum, which we further used to immunise rabbits. We affinity purified IgM and IgY specific reagents from the produced antiserum, and labelled the reagents with horseradish peroxidase. Finally, using the sera of snakes with known exposure to reptarenaviruses we demonstrated that the newly generated reagents can be utilised for serodiagnostic purposes, such as immunoblotting and immunofluorescent staining. To our knowledge, this is the first report to show reptarenavirus-specific antibodies in boa constrictors. PMID- 27355361 TI - Sequence Analysis of In Vivo-Expressed HIV-1 Spliced RNAs Reveals the Usage of New and Unusual Splice Sites by Viruses of Different Subtypes. AB - HIV-1 RNAs are generated through a complex splicing mechanism, resulting in a great diversity of transcripts, which are classified in three major categories: unspliced, singly spliced (SS), and doubly spliced (DS). Knowledge on HIV-1 RNA splicing in vivo and by non-subtype B viruses is scarce. Here we analyze HIV-1 RNA splice site usage in CD4+CD25+ lymphocytes from HIV-1-infected individuals through pyrosequencing. HIV-1 DS and SS RNAs were amplified by RT-PCR in 19 and 12 samples, respectively. 13,108 sequences from HIV-1 spliced RNAs, derived from viruses of five subtypes (A, B, C, F, G), were identified. In four samples, three of non-B subtypes, five 3' splice sites (3'ss) mapping to unreported positions in the HIV-1 genome were identified. Two, designated A4i and A4j, were used in 22% and 25% of rev RNAs in two viruses of subtypes B and A, respectively. Given their close proximity (one or two nucleotides) to A4c and A4d, respectively, they could be viewed as variants of these sites. Three 3'ss, designated A7g, A7h, and A7i, located 20, 32, and 18 nucleotides downstream of A7, respectively, were identified in a subtype C (A7g, A7h) and a subtype G (A7i) viruses, each in around 2% of nef RNAs. The new splice sites or variants of splice sites were associated with the usual sequence features of 3'ss. Usage of unusual 3'ss A4d, A4e, A5a, A7a, and A7b was also detected. A4f, previously identified in two subtype C viruses, was preferentially used by rev RNAs of a subtype C virus. These results highlight the great diversity of in vivo splice site usage by HIV-1 RNAs. The fact that four of five newly identified splice sites or variants of splice sites were detected in non-subtype B viruses allows anticipating an even greater diversity of HIV-1 splice site usage than currently known. PMID- 27355362 TI - Pneumococcal Competence Coordination Relies on a Cell-Contact Sensing Mechanism. AB - Bacteria have evolved various inducible genetic programs to face many types of stress that challenge their growth and survival. Competence is one such program. It enables genetic transformation, a major horizontal gene transfer process. Competence development in liquid cultures of Streptococcus pneumoniae is synchronized within the whole cell population. This collective behavior is known to depend on an exported signaling Competence Stimulating Peptide (CSP), whose action generates a positive feedback loop. However, it is unclear how this CSP dependent population switch is coordinated. By monitoring spontaneous competence development in real time during growth of four distinct pneumococcal lineages, we have found that competence shift in the population relies on a self-activated cell fraction that arises via a growth time-dependent mechanism. We demonstrate that CSP remains bound to cells during this event, and conclude that the rate of competence development corresponds to the propagation of competence by contact between activated and quiescent cells. We validated this two-step cell-contact sensing mechanism by measuring competence development during co-cultivation of strains with altered capacity to produce or respond to CSP. Finally, we found that the membrane protein ComD retains the CSP, limiting its free diffusion in the medium. We propose that competence initiator cells originate stochastically in response to stress, to form a distinct subpopulation that then transmits the CSP by cell-cell contact. PMID- 27355363 TI - Deciphering the Draft Genome of Toxoplasma gondii RH Strain. AB - Toxoplasmosis is a widespread parasitic infection by Toxoplasma gondii, a parasite with at least three distinct clonal lineages. This article reports the whole genome sequencing and de novo assembly of T. gondii RH (type I representative strain), as well as genome-wide comparison across major T. gondii lineages. Genomic DNA was extracted from tachyzoites of T. gondii RH strain and its identity was verified by PCR and LAMP. Subsequently, whole genome sequencing was performed, followed by sequence filtering, genome assembly, gene annotation assignments, clustering of gene orthologs and phylogenetic tree construction. Genome comparison was done with the already archived genomes of T. gondii. From this study, the genome size of T. gondii RH strain was found to be 69.35Mb, with a mean GC content of 52%. The genome shares high similarity to the archived genomes of T. gondii GT1, ME49 and VEG strains. Nevertheless, 111 genes were found to be unique to T. gondii RH strain. Importantly, unique genes annotated to functions that are potentially critical for T. gondii virulence were found, which may explain the unique phenotypes of this particular strain. This report complements the genomic archive of T. gondii. Data obtained from this study contribute to better understanding of T. gondii and serve as a reference for future studies on this parasite. PMID- 27355364 TI - Costs and Benefits of Orthographic Inconsistency in Reading: Evidence from a Cross-Linguistic Comparison. AB - We compared reading acquisition in English and Italian children up to late primary school analyzing RTs and errors as a function of various psycholinguistic variables and changes due to experience. Our results show that reading becomes progressively more reliant on larger processing units with age, but that this is modulated by consistency of the language. In English, an inconsistent orthography, reliance on larger units occurs earlier on and it is demonstrated by faster RTs, a stronger effect of lexical variables and lack of length effect (by fifth grade). However, not all English children are able to master this mode of processing yielding larger inter-individual variability. In Italian, a consistent orthography, reliance on larger units occurs later and it is less pronounced. This is demonstrated by larger length effects which remain significant even in older children and by larger effects of a global factor (related to speed of orthographic decoding) explaining changes of performance across ages. Our results show the importance of considering not only overall performance, but inter individual variability and variability between conditions when interpreting cross linguistic differences. PMID- 27355365 TI - Anti-Phospholipase A2 Receptor (PLA2R) Antibody and Glomerular PLA2R Expression in Japanese Patients with Membranous Nephropathy. AB - The phospholipase A2 receptor (PLA2R) is the major target antigen (Ag) in idiopathic membranous nephropathy (IMN). Recently, several types of immunoassay systems for anti-PLA2R antibody (Ab) have been developed. However, the correlation of serum anti-PLA2R Abs and glomerular expression of PLA2R Ag, and their association with clinicopathological characteristics have yet to be proven in Japanese patients. We examined serum anti-PLA2R Abs by both ELISA and cell based indirect immunofluorescence assay (CIIFA), and glomerular PLA2R expression by immunofluorescence (IF) in 59 biopsy-proven MN patients including IMN (n = 38) and secondary MN (SMN) (n = 21). In this study, anti-PLA2R Abs were present in 50% of IMN patients, but was absent in SMN patients. The concordance rate between ELISA and CIIFA was 100%. Serum IgG levels were significantly lower in anti-PLA2R Ab-positive patients. Serum albumin levels correlated inversely with serum anti PLA2R Ab titers. The prevalence and intensity of glomerular staining for IgG4 by IF were significantly higher in anti-PLA2R Ab-positive patients than in -negative patients. Glomerular PLA2 Ag expression evaluated by IF was positive in 52.6% of IMN patients, but was absent in SMN patients. The concordance rate between the prevalence of glomerular PLA2R Ag expression and anti-PLA2R Ab was 84.2%. The prevalence of anti-PLA2R Abs measured by ELISA/CIIFA was equivalent to previous Japanese studies evaluated using Western blotting. These analyses showed an excellent specificity for the diagnosis of IMN, and anti-PLA2R positivity was associated with some clinicopathological features, especially glomerular IgG4 dominant deposition. PMID- 27355366 TI - Melanoma cell adhesion molecule as an emerging biomarker with prognostic significance in systolic heart failure. AB - BACKGROUND: Melanoma cell adhesion molecule (MCAM) is a marker of endothelial damage. MCAM diagnostic and prognostic value was assessed in chronic heart failure (CHF). MATERIALS & METHODS: 130 CHF patients and 32 controls were included in the study. Telephone follow-up lasted one year. End points were: death from all causes, and hospitalization with CHF exacerbation. RESULTS: MCAM was higher in patients than in controls (p = 0.01). Receiver operator curve analysis revealed that MCAM may serve as a predictor of death (area under the curve: 0.8404; p < 0.002). Patients with MCAM above 500 ng/ml had worse prognosis (p = 0.03). NT-proBNP and age were independent predictors of death in multivariate analysis. CONCLUSION: The increased MCAM indicates endothelial damage in CHF and may serve as a marker of worse prognosis in these patients. PMID- 27355367 TI - Spatial and Temporal Variation in the Effects of Climatic Variables on Dugong Calf Production. AB - Knowledge of the relationships between environmental forcing and demographic parameters is important for predicting responses from climatic changes and to manage populations effectively. We explore the relationships between the proportion of sea cows (Dugong dugon) classified as calves and four climatic drivers (rainfall anomaly, Southern Oscillation El Nino Index [SOI], NINO 3.4 sea surface temperature index, and number of tropical cyclones) at a range of spatially distinct locations in Queensland, Australia, a region with relatively high dugong density. Dugong and calf data were obtained from standardized aerial surveys conducted along the study region. A range of lagged versions of each of the focal climatic drivers (1 to 4 years) were included in a global model containing the proportion of calves in each population crossed with each of the lagged versions of the climatic drivers to explore relationships. The relative influence of each predictor was estimated via Gibbs variable selection. The relationships between the proportion of dependent calves and the climatic drivers varied spatially and temporally, with climatic drivers influencing calf counts at sub-regional scales. Thus we recommend that the assessment of and management response to indirect climatic threats on dugongs should also occur at sub regional scales. PMID- 27355368 TI - HIF-1alpha Deficiency Attenuates the Cardiomyogenesis of Mouse Embryonic Stem Cells. AB - Cardiac cell formation, cardiomyogenesis, is critically dependent on oxygen availability. It is known that hypoxia, a reduced oxygen level, modulates the in vitro differentiation of pluripotent cells into cardiomyocytes via hypoxia inducible factor-1alpha (HIF-1alpha)-dependent mechanisms. However, the direct impact of HIF-1alpha deficiency on the formation and maturation of cardiac-like cells derived from mouse embryonic stem cells (mESC) in vitro remains to be elucidated. In the present study, we demonstrated that HIF-1alpha deficiency significantly altered the quality and quantity of mESC-derived cardiomyocytes. It was accompanied with lower mRNA and protein levels of cardiac cell specific markers (myosin heavy chains 6 and 7) and with a decreasing percentage of myosin heavy chain alpha and beta, and cardiac troponin T-positive cells. As to structural aspects of the differentiated cardiomyocytes, the localization of contractile proteins (cardiac troponin T, myosin heavy chain alpha and beta) and the organization of myofibrils were also different. Simultaneously, HIF-1alpha deficiency was associated with a lower percentage of beating embryoid bodies. Interestingly, an observed alteration in the in vitro differentiation scheme of HIF-1alpha deficient cells was accompanied with significantly lower expression of the endodermal marker (hepatic nuclear factor 4 alpha). These findings thus suggest that HIF-1alpha deficiency attenuates spontaneous cardiomyogenesis through the negative regulation of endoderm development in mESC differentiating in vitro. PMID- 27355369 TI - Modeling Nitrogen Losses in Conventional and Advanced Soil-Based Onsite Wastewater Treatment Systems under Current and Changing Climate Conditions. AB - Most of the non-point source nitrogen (N) load in rural areas is attributed to onsite wastewater treatment systems (OWTS). Nitrogen compounds cause eutrophication, depleting the oxygen in marine ecosystems. OWTS rely on physical, chemical and biological soil processes to treat wastewater and these processes may be affected by climate change. We simulated the fate and transport of N in different types of OWTS drainfields, or soil treatment areas (STA) under current and changing climate scenarios, using 2D/3D HYDRUS software. Experimental data from a mesocosm-scale study, including soil moisture content, and total N, ammonium (NH4+) and nitrate (NO3-) concentrations, were used to calibrate the model. A water content-dependent function was used to compute the nitrification and denitrification rates. Three types of drainfields were simulated: (1) a pipe and-stone (P&S), (2) advanced soil drainfields, pressurized shallow narrow drainfield (PSND) and (3) Geomat (GEO), a variation of SND. The model was calibrated with acceptable goodness-of-fit between the observed and measured values. Average root mean square error (RSME) ranged from 0.18 and 2.88 mg L-1 for NH4+ and 4.45 mg L-1 to 9.65 mg L-1 for NO3- in all drainfield types. The calibrated model was used to estimate N fluxes for both conventional and advanced STAs under current and changing climate conditions, i.e. increased soil temperature and higher water table. The model computed N losses from nitrification and denitrification differed little from measured losses in all STAs. The modeled N losses occurred mostly as NO3- in water outputs, accounting for more than 82% of N inputs in all drainfields. Losses as N2 were estimated to be 10.4% and 9.7% of total N input concentration for SND and Geo, respectively. The highest N2 losses, 17.6%, were estimated for P&S. Losses as N2 increased to 22%, 37% and 21% under changing climate conditions for Geo, PSND and P&S, respectively. These findings can provide practitioners with guidelines to estimate N removal efficiencies for traditional and advanced OWTS, and predict N loads and spatial distribution for identifying non-point sources. Our results show that N losses on OWTS can be modeled successfully using HYDRUS. Furthermore, the results suggest that climate change may increase the removal of N as N2 in the drainfield, with the magnitude of the effect depending on a drainfield type. PMID- 27355370 TI - A first-principles study of pressure-induced phase transformation in a rare-earth formate framework. AB - Among the panoply of exciting properties that metal-organic frameworks (MOFs) exhibit, fully reversible pressure-induced phase transformations (PIPTs) are particularly interesting as they intrinsically relate to the flexibility of MOFs. Recently, a number of MOFs have been reported to exhibit this feature, which is attributed to bond rearrangement with applied pressure. However, the experimental assessment of whether a given MOF exhibits PIPT or not requires sophisticated instruments as well as detailed structural investigations. Can we capture such low pressure transformations through simulations is the question we seek to answer in this paper. For this, we have performed first-principles calculations based on the density functional theory, on a MOF, [tmenH2][Y(HCOO)4]2 (tmenH2(2+) = N,N,N',N'-tetramethylethylenediammonium). The estimated lattice constants for both the parent and product phases of the PIPT agree well with the earlier experimental results available for the same MOF with erbium. Importantly, the results confirm the observed PIPT, and thus provide theoretical corroborative evidence for the experimental findings. Our calculations offer insights into the energetics involved and reveal that the less dense phase is energetically more stable than the denser phase. From detailed analyses of the two phases, we correlate the changes in bonding and electronic structure across the PIPT with elastic and electronic conduction behavior that can be verified experimentally, to develop a deeper understanding of the PIPT in MOFs. PMID- 27355371 TI - The Feasibility of Tracheal Oxygen Supplementation during Flexible Bronchoscopy. AB - BACKGROUND: Hypoxemia is a frequent adverse event occurring during flexible bronchoscopy and is usually prevented by close monitoring and, if needed, oxygen supplementation by nasal cannula. OBJECTIVE: We aim to demonstrate that tracheal oxygen supplementation during flexible bronchoscopy is a feasible, safe and effective method to restore oxygen saturation levels after oxygen desaturation. METHODS: In a first phase, we compare oxygen supplementation by the tracheal or nasal route in a single blinded cross-over design in healthy volunteers. In a second phase, we study patients referred for diagnostic flexible bronchoscopy, who desaturate despite oxygen supplementation by nasal cannula, in order to assess the ability to correct hypoxemia through tracheal oxygen supplementation. RESULTS: In the first phase, the mean capillary partial pressure of oxygen was 181 mm Hg when oxygen at a flow rate of 4 liters/min was administered by the tracheal route, compared to 125 mm Hg by the nasal route (p < 0.001). The capillary partial pressure of carbon dioxide was not significantly different. During 950 bronchoscopic procedures in the second phase of the trial, 30 patients desaturated below 90% despite oxygen supplementation by nasal cannula. In 22 out of these 30 patients, switching to the tracheal route resulted in a correction of the saturation within 120 s. In the remaining 8 patients, saturation levels were corrected after increasing the oxygen flow rate to 4 liters/min. After restoring saturation levels, the bronchoscopy could be completed in 25 of 30 patients. CONCLUSIONS: Tracheal oxygen supplementation is safe, feasible and an effective way to restore oxygen saturation levels during flexible bronchoscopy. PMID- 27355372 TI - A socio-ecological approach for examining factors related to contraceptive use among recent Latina immigrants in an emerging Latino state. AB - Using the Social Ecological Model, the individual, partner, social, and structural factors related to recent Latina immigrants' contraceptive use in an emerging immigrant community were explored. During September 2013-January 2014, door-to-door sampling was used in Birmingham, Alabama to recruit Latina immigrants who had lived in the United States (U.S.) for less than 5 years. Ten women with foreign-born children and 10 with only U.S.-born children completed in depth interviews about their contraceptive use following migration. Women's narratives revealed interrelated barriers to using highly effective contraception after migrating to the U.S. Women had nuanced concerns about using hormonal contraception, which, when combined with other factors, led them to rely on condoms and withdrawal. Limited partner communication was a barrier to effective method use for some women, but partner attitudes that women should be responsible for contraception were less important. Weak female networks made it difficult for immigrants to learn about the U.S. health-care system, especially those with only U.S.-born children. Even once women accessed services, a full range of highly effective methods was not available or affordable. In emerging communities, integrated strategies that address immigrants' need for information and ensure access to affordable contraception would help women achieve their reproductive life goals. PMID- 27355374 TI - Controlled self-organization of cyanostilbene: emission tuning and photo responsiveness. AB - Cyanostilbene modified with dimethylaniline (CMD) could self-assemble into vesicles and fibrous morphologies depending on the solvophobic properties. Furthermore, morphology of well-defined nanostructures could be changed with enhanced emission triggered by the photo-isomerization of cyanostilbene. The present system has potential for building luminescent color conversion materials. PMID- 27355373 TI - Generation and Feasibility Assessment of a New Vehicle for Cell-Based Therapy for Treating Corneal Endothelial Dysfunction. AB - The corneal endothelium maintains corneal transparency by its pump and barrier functions; consequently, its decompensation due to any pathological reason causes severe vision loss due to corneal haziness. Corneal transplantation is the only therapeutic choice for treating corneal endothelial dysfunction, but associated problems, such as a shortages of donor corneas, the difficulty of the surgical procedure, and graft failure, still need to be resolved. Regenerative medicine is attractive to researchers as a means of providing innovative therapies for corneal endothelial dysfunction, as it now does for other diseases. We previously demonstrated the successful regeneration of corneal endothelium in animal models by injecting cultured corneal endothelial cells (CECs) in combination with a Rho kinase (ROCK) inhibitor. The purpose of the present study was to optimize the vehicle for clinical use in cell-based therapy. Our screening of cell culture media revealed that RELAR medium promoted CEC adhesion. We then modified RELAR medium by removing hormones, growth factors, and potentially toxic materials to generate a cell therapy vehicle (CTV) composed of amino acid, salts, glucose, and vitamins. Injection of CECs in CTV enabled efficient engraftment and regeneration of the corneal endothelium in the rabbit corneal endothelial dysfunction model, with restoration of a transparent cornea. The CECs retained >85% viability after a 24 hour preservation as a cell suspension in CTV at 4 degrees C and maintained their potency to regenerate the corneal endothelium in vivo. The vehicle developed here is clinically applicable for cell-based therapy aimed at treating the corneal endothelium. Our strategy involves the generation of vehicle from a culture medium appropriate for a given cell type by removing materials that are not favorable for clinical use. PMID- 27355375 TI - Comprehensive Characterization of the Electronic Structure of U(4+) in Uranium(IV) Phosphate Chloride. AB - Emerald-green single crystals of U(PO4)Cl were grown by chemical vapor transport in a temperature gradient (1000 -> 900 degrees C). The crystal structure of U(PO4)Cl (Cmcm, Z = 4, a = 5.2289(7) A, b = 11.709(2) A, c = 6.9991(8) A) consists of a three-dimensional network of [PO4] tetrahedra and bicapped octahedral [U(IV)O6Cl2] groups. Polarized absorption spectra measured for two perpendicular polarization directions show a large number of well-resolved electronic transitions. These transitions can be fully assigned on the basis of a detailed ligand-field treatment within the framework of the angular overlap model. The magnetic behavior predicted on the basis of the spectroscopic data is in agreement with an f (2) system and perfectly matched by the results of temperature-dependent susceptibility measurements. PMID- 27355376 TI - A Chemical-Genomic Screen of Neglected Antibiotics Reveals Illicit Transport of Kasugamycin and Blasticidin S. AB - Fighting antibiotic resistance requires a deeper understanding of the genetic factors that determine the antibiotic susceptibility of bacteria. Here we describe a chemical-genomic screen in Escherichia coli K-12 that was designed to discover new aspects of antibiotic resistance by focusing on a set of 26 antibiotics and other stresses with poorly characterized mode-of-action and determinants of resistance. We show that the screen identifies new resistance determinants for these antibiotics including a common signature from two antimicrobials, kasugamycin and blasticidin S, used to treat crop diseases like rice blast and fire blight. Following this signature, we further investigated the mechanistic basis for susceptibility to kasugamycin and blasticidin S in E. coli using both genetic and biochemical approaches. We provide evidence that these compounds hijack an overlapping set of peptide ABC-importers to enter the bacterial cell. Loss of uptake may be an underappreciated mechanism for the development of kasugamycin resistance in bacterial plant pathogens. PMID- 27355377 TI - Circulating 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Concentrations and Postoperative Infections in Cardiac Surgical Patients: The CALCITOP-Study. AB - BACKGROUND: Vitamin D has immunomodulatory properties and seems to reduce the risk of infections. Whether low vitamin D concentrations are independent risk factors for nosocomial postoperative infections in surgical patients remains to be studied in detail. METHODS: In 3,340 consecutive cardiac surgical patients, we investigated the association of circulating 25-hydroxyvitamin D (25OHD; indicator of nutritional vitamin D status) and 1,25-dihydroxyvitamin D (1,25[OH]2D; active vitamin D hormone) with nosocomicial infections. The primary endpoint was a composite of thoracic wound infection, sepsis, and broncho-pulmonary infection. Vitamin D status was measured on the last preoperative day. Infections were assessed until discharge. Logistic regression analysis was used to examine the association between vitamin D metabolite concentrations and the composite endpoint. RESULTS: The primary endpoint was reached by 5.6% (n = 186). In patients who reached and did not reach the endpoint, in-hospital mortality was 13.4% and 1.5%, respectively (P<0.001). Median (IQR) 25OHD and 1,25(OH)2D concentrations were 43. 2 (29.7-61.9) nmol/l and 58.0 (38.5-77.5) pmol/l, respectively. Compared with the highest 1,25(OH)2D quintile (>81.0 pmol/l), the multivariable-adjusted odds ratio of infection was 2.57 (95%CI:1.47-4.49) for the lowest 1,25(OH)2D quintile (<31.5 pmol/l) and 1.85 (95%CI:1.05-3.25) for the second lowest quintile (31.5-49.0 pmol/l). There was no significant association between 25OHD concentrations and the primary endpoint. CONCLUSIONS: Our data indicate an independent association of low 1,25(OH)2D levels with the risk of postoperative infections in cardiac surgical patients. Future studies should pay more attention on the clinical relevance of circulating 1,25(OH)2D and its regulation. PMID- 27355378 TI - Structural and Theoretical Investigation of Anhydrous 3,4,5-Triacetoxybenzoic Acid. AB - A comprehensive investigation of anhydrous form of 3,4,5-Triacetoxybenzoic acid (TABA) is reported. Single crystal X-ray diffraction, Thermal analysis, Fourier Transform Infrared spectroscopy (FTIR) and DFT calculations were applied for TABA characterization. This anhydrous phase crystallizes in the triclinic [Formula: see text] space group (Z' = 1) and its packing shows a supramolecular motif in a classical [Formula: see text] ring formed by acid-acid groups association. The phase stability is accounted in terms of supramolecular architecture and its thermal behaviour. Conformation search at B3LYP/6-311++G(2d,p) level of theory shows the existence of three stable conformers and the most stable conformation was found experimentally. The reactivity of TABA was investigated using the molecular orbital theory and molecular electrostatic potential. The calculation results were used to simulate the infrared spectrum. There is a good agreement between calculated and experimental IR spectrum, which allowed the assignment of the normal vibrational modes. PMID- 27355391 TI - Danish multidisciplinary cancer groups - DMCG.dk benchmarking consortium: Article series on cancer survival and mortality in Denmark 1995-2012. PMID- 27355390 TI - The Preoperative Peripheral Blood Monocyte Count Is Associated with Liver Metastasis and Overall Survival in Colorectal Cancer Patients. AB - BACKGROUND: Colorectal cancer (CRC) is the third most common malignancy in males and the second most common in females worldwide. Distant metastases have a strong negative impact on the prognosis of CRC patients. The most common site of CRC metastases is the liver. Both disease progression and metastasis have been related to the patient's peripheral blood monocyte count. We therefore performed a case-control study to assess the relationship between the preoperative peripheral blood monocyte count and colorectal liver metastases (CRLM). METHODS: Clinical data from 117 patients with colon cancer and 93 with rectal cancer who were admitted to the Chinese People's Liberation Army General Hospital (Beijing, China) between December 2003 and May 2015 were analysed retrospectively, with the permission of both the patients and the hospital. RESULTS: Preoperative peripheral blood monocyte counts, the T and N classifications of the primary tumour and its primary site differed significantly between the two groups (P < 0.001, P < 0.001, P = 0.002, P < 0.001), whereas there were no differences in the sex, age, degree of tumour differentiation or largest tumour diameter. Lymph node metastasis and a high preoperative peripheral blood monocyte count were independent risk factors for liver metastasis (OR: 2.178, 95%CI: 1.148~4.134, P = 0.017; OR: 12.422, 95%CI: 5.076~30.398, P < 0.001), although the risk was lower in patients with rectal versus colon cancer (OR: 0.078, 95%CI: 0.020~0.309, P < 0.001). Primary tumour site (P<0.001), degree of tumour differentiation (P = 0.009), T, N and M classifications, TNM staging and preoperative monocyte counts (P<0.001) were associated with the 5-year overall survival (OS) of CRC patients. A preoperative peripheral blood monocyte count > 0.505 * 109 cells/L, high T classification and liver metastasis were independent risk factors for 5-year OS (RR: 2.737, 95% CI: 1.573~ 4.764, P <0.001; RR: 2.687, 95%CI: 1.498~4.820, P = 0.001; RR: 4.928, 95%CI: 2.871~8.457, P < 0.001). CONCLUSIONS: The demonstrated association between preoperative peripheral blood monocyte count and liver metastasis in patients with CRC recommends the former as a useful predictor of postoperative prognosis in CRC patients. PMID- 27355392 TI - Clinical relevance for lowering C-reactive protein with statins. AB - The role of statins in the protection of atherosclerosis and reducting cardiovascular (CV) events is well established. On the other hand, the role of inflammation in the propagation and propensity to CV events has also been demonstrated. High-sensitivity C-reactive protein (CRP) which is involved in the immunologic process of inflammation has received the interest for its use in screening and risk reclassification. However, evidence for its causal relationship with atherothrombosis is lacking, and even more, knowing that statins influence on the reduction of CRP levels, a relevant evidence of their clinical benefits in this regard is also lacking. This article reviews four different key points regarding the issue, to better understand the current state and application of the treatment with statins in order to achieve benefits from lowering CRP's levels regarding CV diseases: (1) the mechanisms of reduction of CRP levels by statins; (2) the role of statin-mediated CRP reduction in the atherosclerotic plaque regression; (3) the role in the prevention of CV diseases; and (4) the role in case of secondary prevention. With this basis, the reduction of CRP levels should be interpreted as a reduction of inflammatory burden thus its clinical benefits could be more interesting in secondary prevention. KEY MESSAGES It could be admitted a role of statin-mediated CRP diminution to reduce the rate of progression in atherosclerotic plaque. In general, and in the absence of specific clinical trials, the role of statins by lowering CRP and consequently, preventing cardiovascular events may be superior in case of secondary prevention because a more pronounced state of inflammation and regardless of its levels at baseline. PMID- 27355393 TI - [Ni(OH)3W6O18(OCH2)3CCH2OH](4-): the first tris-functionalized Anderson-type heteropolytungstate. AB - Na2[TMA]2[Ni(OH)3W6O18(OCH2)3CCH2OH].9H2O represents the first covalent tris functionalized Anderson-type heteropolytungstate and was characterized by single crystal X-ray diffraction, electrospray ionization mass spectrometry, TGA and IR spectroscopy. Zeta potential measurements in solutions containing human serum albumin were performed to investigate electrostatic interactions with [Ni(OH)3W6O18(OCH2)3CCH2OH](4-). PMID- 27355395 TI - Concentration Dependent Specific Rotations of Chiral Surfactants: Experimental and Computational Studies. AB - Recent experimental studies have shown unexpected chiroptical response from some chiral surfactant molecules, where the specific rotations changed significantly as a function of concentration. To establish a theoretical understanding of this experimentally observed phenomena, a novel methodology for studying chiral surfactants via combined molecular dynamics (MD) and quantum mechanical (QM) calculations is presented. MD simulations on the +10 000 atom surfactant systems have been performed using MD and QM/molecular mechanics (MM) approaches. QM calculations performed on MD snapshots coupled with extensive analysis on lauryl ester of phenylalanine (LEP) surfactant system indicate that the experimentally observed variation of specific rotation with concentration may be due to the conformational differences of the surfactant monomers in the aggregates. Though traditional MM simulations did not show significant differences in the conformer populations, QM/MM simulations using the forces derived from the PM6 method did predict conformational differences between aggregated and nonaggregated LEP molecules, which is consistent with experimental data. Additionally the electrostatic environment of charged surfactants may also be important, since dramatic changes in the Boltzmann populations of surfactant monomers can be noted in the presence of an electric field generated by the chiral ionic aggregates. PMID- 27355394 TI - Quality of Care Provided by a Comprehensive Dementia Care Comanagement Program. AB - Multiple studies have shown that quality of care for dementia in primary care is poor, with physician adherence to dementia quality indicators (QIs) ranging from 18% to 42%. In response, the University of California at Los Angeles (UCLA) Health System created the UCLA Alzheimer's and Dementia Care (ADC) Program, a quality improvement program that uses a comanagement model with nurse practitioner dementia care managers (DCM) working with primary care physicians and community-based organizations to provide comprehensive dementia care. The objective was to measure the quality of dementia care that nurse practitioner DCMs provide using the Assessing Care of Vulnerable Elders (ACOVE-3) and Physician Consortium for Performance Improvement QIs. Participants included 797 community-dwelling adults with dementia referred to the UCLA ADC program over a 2 year period. UCLA is an urban academic medical center with primarily fee-for service reimbursement. The percentage of recommended care received for 17 dementia QIs was measured. The primary outcome was aggregate quality of care for the UCLA ADC cohort, calculated as the total number of recommended care processes received divided by the total number of eligible quality indicators. Secondary outcomes included aggregate quality of care in three domains of dementia care: assessment and screening (7 QIs), treatment (6 QIs), and counseling (4 QIs). QIs were abstracted from DCM notes over a 3-month period from date of initial assessment. Individuals were eligible for 9,895 QIs, of which 92% were passed. Overall pass rates of DCMs were similar (90-96%). All counseling and assessment QIs had pass rates greater than 80%, with most exceeding 90%. Wider variation in adherence was found among QIs addressing treatments for dementia, which patient specific criteria triggered, ranging from 27% for discontinuation of medications associated with mental status changes to 86% for discussion about acetylcholinesterase inhibitors. Comprehensive dementia care comanagement with a nurse practitioner can result in high quality of care for dementia, especially for assessment, screening, and counseling. The effect on treatment QIs is more variable but higher than previous reports of physician-provided dementia care. PMID- 27355396 TI - Neurocognitive and behavioral profiles of children with Landau-Kleffner syndrome. AB - This is a retrospective study of 14 cases of children with Landau-Kleffner syndrome (LKS), the most prominent feature of which is acquired aphasia. These children were followed at a tertiary care pediatric epilepsy center. From the research data base, all LKS cases with neuropsychological evaluation were extracted. Children ranged in age from 6 to 13 years (M = 9.12; SD = 2.19) at the time of assessment (1 to 10 years post-onset). The majority of the children were white males, and all but one continued to experience seizure activity. Global intellectual functioning ranged from 59 to 101 (M = 82.07; SD = 12.14). Across the 14 cases reviewed, the neuropsychological profiles are considered in the context of neurological and syndrome-related factors. For these cases, 86% demonstrated continued expressive, and 50% had receptive language problems with 57% exhibiting poor auditory processing. Furthermore, 50 to 57% had deficits in auditory working memory and verbal memory. Academically, the majority had poor reading fluency and comprehension; 50% exhibited difficulty with mathematics. Finally, 57% evidenced attentional or other behavioral problems. Better understanding of LKS can assist in targeted assessment and intervention planning. PMID- 27355397 TI - Plerixafor injection: a hematopoietic stem cell mobilizer in non-Hodgkin lymphoma and multiple myeloma. AB - INTRODUCTION: A combination of granulocyte colony-stimulating factor (G-CSF) and chemotherapy or G-CSF alone are the most common mobilization regimens for autotransplantations. Plerixafor is used for mobilization of CD34(+) cells with G CSF in non-Hodgkin lymphoma (NHL) and myeloma (MM) patients. AREAS COVERED: The available phase II and III data on plerixafor has been reviewed. The efficacy of plerixafor in the mobilization of CD34(+) cells in predicted poor mobilizers as well as in patients who had failed a mobilization has been evaluated. The pre emptive use of plerixafor as well as studies on cost-effectiveness are covered. Also effects in the composition of the collected grafts along with the data on long-term outcome of plerixafor-mobilized patients is discussed. Expert commentary: Plerixafor combined with G-CSF mobilizes CD34(+) cells more efficiently than G-CSF alone in patients with NHL or MM. In phase III studies, engraftment after high-dose therapy has been comparable to G-CSF mobilized patients. The pre-emptive use of plerixafor added to mobilization with chemotherapy plus G-CSF or with G-CSF alone has gained more popularity. This approach may be more cost-effective than the routine use of this drug. The changes observed in the composition of grafts after plerixafor injection may have implications for post-transplant events. PMID- 27355398 TI - Measuring the Real Clinical Impact of Randomized Clinical Trials in Oncology Reply: Beyond Citation Counts. PMID- 27355399 TI - The Association Between Sleep Duration, Insulin Sensitivity, and beta-Cell Function: The EGIR-RISC Study. AB - CONTEXT: In the past decade, over 3 dozen studies reported a relationship between self-reported short sleep and disturbed glucose metabolism. A study with insulin sensitivity assessed according to the gold standard hyperinsulinemic-euglycemic clamp is, however, still missing. OBJECTIVE: To evaluate the cross-sectional association of sleep duration with insulin sensitivity and beta-cell function in the European group for the study of insulin resistance (EGIR-RISC) study cohort. DESIGN, SETTING, PARTICIPANTS, AND MEASURES: We used data from the baseline measurements of the European, multicentre EGIR-RISC study that included 1319 clinically healthy participants. Sleep and physical activity were measured using a single-axis accelerometer. Insulin sensitivity and beta-cell function were estimated by hyperinsulinemic-euglycemic clamp and from the oral glucose insulin sensitivity index model, using an oral glucose tolerance test. Associations of sleep duration with insulin sensitivity and beta-cell function were analyzed by multiple linear regression, stratified by sex. RESULTS: In our current analysis, we included 788 participants (57% women, age 44 +/- 8 y), who had an average sleep duration of 7.3 +/- 1.5 hours. In men, we observed an inverted U-shaped association between sleep duration categorized per hour and M/I (in MUmol/min per kgFFM/nM per hour) (beta-estimate [95% confidence intervals] 41 [2, 80]; P = .04 and beta(2)-estimate -3 [-6, -0.2], P = .04) as well as a trend for the oral glucose insulin sensitivity index (in mL/min per kgFFM) (beta-estimate [95% confidence intervals] 0.8 [-0.4, 2]; P = .17). In women, we observed a U-shaped association between sleep duration and beta-cell function (in pmol/min per m(2)/mM per hour) (beta-estimate -45 [-86, -3]; P = .04 and beta(2)-estimate 3 [0.2, 6]; P = .04). CONCLUSIONS: Sleep duration is associated with insulin sensitivity and beta-cell function in a sex-specific manner in clinically healthy people. PMID- 27355401 TI - Beneficial Effect of Intermedin 1-53 in Septic Shock Rats: Contributions of Rho Kinase and BKCA Pathway-Mediated Improvement in Cardiac Function. AB - OBJECTIVE: Intermedin (IMD) is a calcitonin gene-related peptide shown to have a protective effect on myocardial function in ischemia-reperfusion injury. Whether IMD has beneficial effect in severe sepsis and septic shock (and its underlying mechanisms) is not known. METHODS: We induced septic shock using cecal ligation and puncture (CLP). We focused on the potential beneficial effect of IMD1-53 on cardiac papillary muscle and cardiomyocytes against septic shock and its relationship with the protection of cardiac function. RESULTS: Early (immediately after CLP) and late (12 h after CLP) administration of IMD1-53 (0.5 MUg/kg) improved animal survival significantly, increased cardiac contractility and function, and improved tissue perfusion and oxygen delivery. The effect of early administration of IMD1-53 was better than that of late administration. The Rho kinase/TnI and BKCa pathways participated in the protective effect of IMD1-53 on cardiac function in septic rats. An inhibitor of Rho kinase (Y-27632) or a BKCa opener (NS1619) abolished the protective effect of IMD1-53 on cardiac function. IMD1-53 increased expression of Rho kinase in cardiac muscle and inhibited TnI phosphorylation. IMD1-53 inhibited currents in BKCa channels and intracellular calcium concentration in cardiomyocytes. CONCLUSIONS: IMD1-53 is beneficial against severe sepsis/septic shock. IMD1-53 can improve cardiac contractility and cardiac function significantly, and then improve tissue perfusion and oxygen delivery. Rho kinase and the BKCa pathways have important roles in these effects. These findings provide a new treatment strategy for severe sepsis with cardiac dysfunction. PMID- 27355400 TI - Testosterone Treatment and Sexual Function in Older Men With Low Testosterone Levels. AB - CONTEXT: The Testosterone Trials are a coordinated set of seven trials to determine the efficacy of T in symptomatic men >=65 years old with unequivocally low T levels. Initial results of the Sexual Function Trial showed that T improved sexual activity, sexual desire, and erectile function. OBJECTIVE: To assess the responsiveness of specific sexual activities to T treatment; to relate hormone changes to changes in sexual function; and to determine predictive baseline characteristics and T threshold for sexual outcomes. DESIGN: A placebo-controlled trial. SETTING: Twelve academic medical centers in the United States. PARTICIPANTS: A total of 470 men >=65 years of age with low libido, average T <275 ng/dL, and a partner willing to have sexual intercourse at least twice a month. METHODS: Men were assigned to take T gel or placebo for 1 year. Sexual function was assessed by three questionnaires every 3 months: the Psychosexual Daily Questionnaire, the Derogatis Interview for Sexual Function, and the International Index of Erectile Function. RESULTS: Compared with placebo, T administration significantly improved 10 of 12 measures of sexual activity. Incremental increases in total and free T and estradiol levels were associated with improvements in sexual activity and desire, but not erectile function. No threshold T level was observed for any outcome, and none of the 27 baseline characteristics predicted responsiveness to T. CONCLUSIONS: In older men with low libido and low T levels, improvements in sexual desire and activity in response to T treatment were related to the magnitude of increases in T and estradiol levels, but there was no clear evidence of a threshold effect. PMID- 27355402 TI - Complement Activation in Trauma Patients Alters Platelet Function. AB - Trauma remains the main cause of death for both civilians and those in uniform. Trauma-associated coagulopathy is a complex process involving inflammation, coagulation, and platelet dysfunction. It is unknown whether activation of complement, which occurs invariably in trauma patients, is involved in the expression of trauma-associated coagulopathy. We designed a prospective study in which we enrolled 40 trauma patients and 30 healthy donors upon arrival to the emergency department of BIDMC. Platelets from healthy individuals were incubated with sera from trauma patients and their responsiveness to a thrombin receptor activating peptide was measured using aggregometry. Complement deposition on platelets from trauma patients was measured by flow cytometry. Normal platelets displayed hypoactivity after incubation with trauma sera even though exposure to trauma sera resulted in increased agonist-induced calcium flux. Depletion of complement from sera further blocked activation of hypoactive platelets. Conversely, complement activation increased aggregation of platelets. Platelets from trauma patients were found to have significantly higher amounts of C3a and C4d on their surface compared with platelets from controls. Depletion of complement (C4d, C3a) reversed the ability of trauma sera to augment agonist induced calcium flux in donor platelets. Our data indicate that complement enhances platelet aggregation. Despite its complement content, trauma sera render platelets hypoactive and complement depletion further blocks activation of hypoactive platelets. The defect in platelet activation induced by trauma sera is distal to receptor activation since agonist-induced Ca2+ flux is elevated in the presence of trauma sera owing to complement deposition. PMID- 27355403 TI - The Beneficial Effects of ETS-GS, a Novel Vitamin E Derivative, on a Rat Model of Crush Injury. AB - Crush syndrome is a devastating condition leading to multiple organ failure. The mechanisms by which local traumatic injuries affect distant organs remain unknown. ETS-GS is a novel water-soluble, stable anti-oxidative agent composed of vitamin E derivative. Given that one of the main pathophysiological effects in crush syndrome is massive ischemia-reperfusion, reactive oxygen species (ROS) generated from the injured extremities would be systemically involved in distant organ damage. We investigated whether ETS-GS could suppress inflammatory response and improve mortality in a rat model of crush injury. Crush injury was induced by compression of bilateral hindlimbs for 6 h followed by release of compression. Seven-day survival was significantly improved by ETS-GS treatment. To estimate anti-oxidative and anti-inflammatory effects of ETS-GS, serum was collected 6 and 20 h after the injury. ETS-GS treatment significantly dampened the up-regulation of malondialdehyde and reduction of superoxide dismutase in the serum, which were induced by crush injury. Serum levels of interleukin 6 and high mobility group box 1 were significantly decreased in the ETS-GS group compared with those in the control group. Lung damage shown by hematoxylin-eosin staining at 20 h after the injury was ameliorated by the treatment. Ex vivo imaging confirmed that ETS-GS treatment reduced ROS generation in both the lung and the muscle following crush injury. The administration of ETS-GS could suppress ROS generation, systemic inflammation, and the subsequent organ damage, thus improving survival in a rat model of crush injury. These findings suggest that ETS-GS can become a novel therapeutic agent against crush injury. PMID- 27355405 TI - Synthesis of beta-Branched Tryptophan Analogues Using an Engineered Subunit of Tryptophan Synthase. AB - We report that l-threonine may substitute for l-serine in the beta-substitution reaction of an engineered subunit of tryptophan synthase from Pyrococcus furiosus, yielding (2S,3S)-beta-methyltryptophan (beta-MeTrp) in a single step. The trace activity of the wild-type beta-subunit on this substrate was enhanced more than 1000-fold by directed evolution. Structural and spectroscopic data indicate that this increase is correlated with stabilization of the electrophilic aminoacrylate intermediate. The engineered biocatalyst also reacts with a variety of indole analogues and thiophenol for diastereoselective C-C, C-N, and C-S bond forming reactions. This new activity circumvents the 3-enzyme pathway that produces beta-MeTrp in nature and offers a simple and expandable route to preparing derivatives of this valuable building block. PMID- 27355408 TI - Improved Photovoltaic Characteristics and Grain Boundary Potentials of CuIn0.7Ga0.3Se2 Thin Films Spin-Coated by Na-Dissolved Nontoxic Precursor Solution. AB - This work introduces the incorporation of Na into the nontoxic precursor solution of CIGS to improve photovoltaic cell performance with the optimized benefits of Na. The extensive incorporation range of 0.05 to 0.5 mol % Na is used for the simple spin-coating process of high quality absorber thin films. A cell efficiency of ~8.21%, which corresponds to an improvement of ~10.2% compared to the reference sample, is achieved for the 0.25 mol % Na sample with enhanced open circuit voltage and fill factor. The improvement was further analyzed as related to InCu defects and grain boundary potentials. PMID- 27355406 TI - Differences in Obesity Rates Among Minority and White Women: The Latent Role of Maternal Stress. AB - White and minority women experience different rates of obesity in the United States. Yet our understanding of the dynamics that give rise to this gap remains limited. This article presents a conceptual framework that considers pathways leading to these different rates. It draws upon the life-course perspective, allostatic load, and the weathering hypothesis to identify pathways linking childbearing, stress, and obesity. This conceptual framework extends prior work by identifying age at first birth as an important parameter that influences these pathways. Empirical evidence to test these pathways is needed. PMID- 27355404 TI - Integration of Breast Cancer Secretomes with Clinical Data Elucidates Potential Serum Markers for Disease Detection, Diagnosis, and Prognosis. AB - Cancer cells secrete factors that influence adjacent cell behavior and can lead to enhanced proliferation and metastasis. To better understand the role of these factors in oncogenesis and disease progression, estrogen and progesterone receptor positive MCF-7 cells, triple negative breast cancer MDA-MB-231, DT22, and DT28 cells, and MCF-10A non-transformed mammary epithelial cells were grown in 3D cultures. A special emphasis was placed on triple negative breast cancer since these tumors are highly aggressive and no targeted treatments are currently available. The breast cancer cells secreted factors of variable potency that stimulated proliferation of the relatively quiescent MCF-10A cells. The conditioned medium from each cell line was subjected to mass spectrometry analysis and a variety of secreted proteins were identified including glycolytic enzymes, proteases, protease inhibitors, extracellular matrix proteins, and insulin-like growth factor binding proteins. An investigation of the secretome from each cell line yielded clues about strategies used for breast cancer proliferation and metastasis. Some of the proteins we identified may be useful in the development of a serum-based test for breast cancer detection, diagnosis, prognosis, and monitoring. PMID- 27355409 TI - Zika Virus. PMID- 27355410 TI - Zika Virus. AB - To the Editor: Petersen et al. (April 21 issue)1 provide a detailed review of Zika virus. We have some concern regarding diagnostic criteria for microcephaly in fetuses and newborns exposed to the virus. According to the Centers for Disease Control and Prevention (CDC) recommendation that microcephaly should be defined as an occipitofrontal circumference below the third percentile, nearly 3% of newborns would be categorized as having microcephaly. In Brazil, where there are 3 million live births per year, the application of this definition would result in nearly 90,000 infants being labeled as having microcephaly - a far greater number than . . . PMID- 27355411 TI - Zika Virus. PMID- 27355412 TI - An Ethylene-Bridged Phosphane/Borane Frustrated Lewis Pair Featuring the B(Fxyl)2 Lewis Acid Component. AB - Hydroboration of dimesitylvinylphosphane with bis[3,5 bis(trifluoromethyl)phenyl]borane [HB(Fxyl)2 ] gave the intramolecular ethylene bridged P/B frustrated Lewis pair (FLP) Mes2 PCH2 CH2 B(Fxyl)2 . The new compound underwent a variety of typical FLP reactions such as P/B-addition to the carbonyl group of p-chloro-benzaldehyde. Cooperative N,N-addition to nitric oxide gave the respective persistent P/B FLPNO(.) radical, which readily reacted with 1,4 cyclohexadiene by H-atom abstraction to yield the corresponding P/B FLPNOH product. The B(Fxyl)2 -containing FLP reacted as a template for the HB(C6 F5 )2 reduction of carbon monoxide to the formyl stage to give the respective FLP(eta(2) -formylborane) product. Most products were characterized by single crystal X-ray crystal structure analysis. PMID- 27355413 TI - Organic Phase Syntheses of Magnetic Nanoparticles and Their Applications. AB - In the past two decades, the synthetic development of magnetic nanoparticles (NPs) has been intensively explored for both fundamental scientific research and technological applications. Different from the bulk magnet, magnetic NPs exhibit unique magnetism, which enables the tuning of their magnetism by systematic nanoscale engineering. In this review, we first briefly discuss the fundamental features of magnetic NPs. We then summarize the synthesis of various magnetic NPs, including magnetic metal, metallic alloy, metal oxide, and multifunctional NPs. We focus on the organic phase syntheses of magnetic NPs with precise control over their sizes, shapes, compositions, and structures. Finally we discuss the applications of various magnetic NPs in sensitive diagnostics and therapeutics, high-density magnetic data recording and energy storage, as well as in highly efficient catalysis. PMID- 27355414 TI - A Depot Medroxyprogesterone Acetate Dose That Models Human Use and Its Effect on Vaginal SHIV Acquisition Risk. AB - INTRODUCTION: Hormonal contraception with depot medroxyprogesterone acetate (DMPA) may increase HIV acquisition risk, but observational human studies are inconclusive, and animal models can help investigate this risk. In this study, we test the impact of a low DMPA dose, designed to resemble human contraceptive use, on Simian-Human Immunodeficiency Virus (SHIV) acquisition risk in pigtail macaques (Macaca nemestrina). METHODS: Macaques metabolize DMPA faster than humans. We previously identified a per-weight DMPA dose and administration frequency that achieves long-lasting suppression of ovulation in macaques. Eight macaques were given 1.5-mg/kg DMPA monthly, whereas 11 were untreated controls. For comparison, women receive 150 mg (approximately 2 mg/kg) every 3 months. We exposed monkeys to 20 suboptimal SHIV challenges, designed to slowly infect half of controls and allow increased infection in the DMPA group. RESULTS: It took a median 5.5 viral challenges to infect DMPA-treated macaques and 9 challenges for controls (P = 0.27; exact conditional logistic regression). The exact odds ratio was 2.2 (CI: 0.6 to 8.3). Ovulation was suppressed, and the vaginal epithelium was thinned after DMPA treatment in all animals (mean, 30 and 219 mm in DMPA treated and control macaques, respectively, P = 0.03, t test using the Satterthwaite degrees-of-freedom approximation). CONCLUSIONS: SHIV infections in DMPA-treated macaques were 2.2 times those of controls, but this was not statistically significant. The result is remarkably similar to studies of human DMPA use, which have shown HIV risk increases of a similar magnitude and of variable significance. Taken together with previous studies of higher DMPA doses in macaques, the results suggest a dose-dependent effect of DMPA on Simian Immunodeficiency Virus (SIV) or SHIV acquisition. PMID- 27355416 TI - Paramagnetic properties of Fe-Mn and Fe-V alloys: a DMFT study. AB - We calculate magnetic susceptibility of paramagnetic bcc Fe-Mn and Fe-V alloys by two different approaches. The first approach employs the coherent potential approximation (CPA) combined with the dynamical mean-field theory (DMFT). The material-specific Hamiltonians in the Wannier function basis are obtained by density functional theory. In the second approach, we construct supercells modeling the binary alloys and study them using DMFT. Both approaches lead to a qualitative agreement with experimental data. In particular, the decrease of Curie temperature with Mn content and a maximum at about 10 at.% V are well described in units of the Curie temperature of pure iron. In contrast to the Mn impurities, the V ones are found to be antiferromagnetically coupled to Fe atoms. Our calculations for the two-band Anderson-Hubbard model indicate that the antiferromagnetic coupling is responsible for a maximum in the concentration dependence of Curie temperature in Fe-V alloys. PMID- 27355415 TI - Treatment Outcomes and Resistance Patterns of Children and Adolescents on Second Line Antiretroviral Therapy in Asia. AB - BACKGROUND: Data on pediatric treatment outcomes and drug resistance while on second-line antiretroviral therapy (ART) are needed to guide HIV care in resource limited countries. METHODS: HIV-infected children <18 years who were switched or switching to second-line ART after first-line failure were enrolled from 8 sites in Indonesia, Thailand, and Vietnam. Genotyping was performed at virologic failure (VF; HIV-RNA >1000 copies/mL). Cox proportional hazards regression was used to evaluate factors predicting VF. RESULTS: Of 277 children, 41% were female. At second-line switch, age was 7.5 (5.3-10.3) years, CD4 count was 300 (146-562) cells per cubic millimeter, and percentage was 13 (7-20%); HIV-RNA was 5.0 (4.4-5.5) log10 copies per milliliter. Second-line regimens contained lamivudine (90%), tenofovir (43%), zidovudine or abacavir (30%), lopinavir (LPV/r; 91%), and atazanavir (ATV; 7%). After 3.3 (1.8-5.3) years on second-line ART, CD4 was 763 (556-1060) cells per cubic millimeter and 26% (20-31%). VF occurred in 73 (27%), with an incidence of 7.25 per 100 person-years (95% confidence interval [CI]: 5.77 to 9.12). Resistance mutations in 50 of 73 children with available genotyping at first VF included M184V (56%), >=1 thymidine analogue mutation (TAM; 40%), >=4 TAMs (10%), Q151M (4%), any major LPV mutation (8%), >=6 LPV mutations (2%), and any major ATV mutation (4%). Associations with VF included age >11 years (hazard ratio [HR] 4.06; 95% CI: 2.15 to 7.66) and HIV-RNA >5.0 log10 copies per milliliter (HR 2.42; 95% CI: 1.27 to 4.59) at switch and were seen more commonly in children from Vietnam (HR 2.79; 95% CI: 1.55 to 5.02). CONCLUSIONS: One-fourth of children developed VF while on second-line ART. However, few developed major mutations to protease inhibitors. PMID- 27355417 TI - Emerging adsorptive removal of azo dye by metal-organic frameworks. AB - Adsorptive removal of toxic compounds using advanced porous materials is one of the most attractive approaches. In recent years, the metal-organic frameworks (MOFs), a subset of advanced porous nano-structured materials, due to their unique characteristics are showing great promise for better adsorption/separation of various water contaminants. Given the importance of azo dye removal, as an important class of pollutants, this paper aims to review and summarize the recently published research on the effectiveness of various MOFs adsorbents under different physico-chemical process parameters in dyes adsorption. The effect of pH, the adsorption mechanism and the applicability of various adsorption kinetic and thermodynamic models are briefly discussed. Most of the results observed showed that the adsorption kinetic and isotherm of azo dyes onto the MOFs mostly followed the pseudo-second order and Langmuir models respectively. Also, the optimum pH value for the removal of majority of azo dyes by MOFs was observed to be in the range of ~5-7. PMID- 27355418 TI - Aqueous solubilities of five N-(diethylaminothiocarbonyl)benzimido derivatives at T = 298.15 K. AB - N-(diethylaminothiocarbonyl)benzimido derivatives are polar multifunctional substances. A set of these compounds was synthesised by successive substitution on the enamine side, resulting in similar substances with different polarities, providing a set of model compounds with respect to the study of substituent effects on physico-chemical properties. Experimental aqueous solubility data, at T = 298.15 K, of N-(diethylaminothiocarbonyl)benzamidine, PhCNH2NCSNEt2 (1),N (diethylaminothiocarbonyl)-N'-phenylbenzamidine, PhCNHPhNCSNEt2 (2), N (diethylaminothiocarbonyl)-N'-monoethylbenzamidine, PhCNHEtNCSNEt2 (3), N (diethylaminothiocarbonyl)-N',N'-diethylbenzamidine, PhCNEt2NCSNEt2 (4), and N (diethylaminothiocarbonyl)benzimido ethylester, PhCOEtNCSNEt2 (5) were measured at T = 298.15 K. The obtained data are supplemented by COSMO-RS aqueous solubility predictions as well as other environmentally important partition coefficients. This information is shown in a two-dimensional chemical space diagram, providing indications about the compartment into which the bulk of the compounds is likely to concentrate. The expected quality of COSMO-RS predictions for this type of screening exercise is illustrated on a set of pesticides with established thermophysical property data. PMID- 27355419 TI - Is the heart still in danger after stopping CPAP? PMID- 27355420 TI - Low-Energy Electron-Induced Transformations in Organolead Halide Perovskite. AB - Methylammonium lead iodide perovskite (MAPbI3 ), a prototype material for potentially high-efficient and low-cost organic-inorganic hybrid perovskite solar cells, has been investigated intensively in recent years. A study of low-energy electron-induced transformations in MAPbI3 is presented, performed by combining controlled electron-impact irradiation with X-ray photoelectron spectroscopy and scanning electron microscopy. Changes were observed in both the elemental composition and the morphology of irradiated MAPbI3 thin films as a function of the electron fluence for incident energies from 4.5 to 60 eV. The results show that low-energy electrons can affect structural and chemical properties of MAPbI3 . It is proposed that the transformations are triggered by the interactions with the organic part of the material (methylammonium), resulting in the MAPbI3 decomposition and aggregation of the hydrocarbon layer. PMID- 27355421 TI - Regulation of osteoclast differentiation by static magnetic fields. AB - Static magnetic field (SMF) modulates bone metabolism, but little research is concerned with the effects of SMF on osteoclast. Our previous studies show that osteogenic differentiation is strongly correlated with magnetic strength from hypo (500 nT), weak (geomagnetic field, GMF), moderate (0.2 T) to high (16 T) SMFs. We speculated that the intensity that had positive (16 T) or negative (500 nT and 0.2 T) effects on osteoblast differentiation would inversely influence osteoclast differentiation. To answer this question, we examined the profound effects of SMFs on osteoclast differentiation from pre-osteoclast Raw264.7 cells. Here, we demonstrated that 500 nT and 0.2 T SMFs promoted osteoclast differentiation, formation and resorption, while 16 T had an inhibitory effect. Almost all the osteoclastogenic genes were highly expressed under 500 nT and 0.2 T, including RANK, matrix metalloproteinase 9 (MMP9), V-ATPase, carbonic anhydrase II (Car2) and cathepsin K (CTSK), whereas they were decreased under 16 T. In addition, 16 T disrupted actin formation with remarkably decreased integrin beta3 expression. Collectively, these results indicate that osteoclast differentiation could be regulated by altering the intensity of SMF, which is just contrary to that on osteoblast differentiation. Therefore, studies of SMF effects could reveal some parameters that could be used as a physical therapy for various bone disorders. PMID- 27355422 TI - Circulation Enrichment of Functional Endothelial Progenitor Cells by Infantile Phototherapy. AB - Phototherapy is the most common therapy used for severe jaundice. There is increasing evidence that phototherapy can directly affect the expression and function of cell surface receptors including adhesion molecules, cytokines, and growth factor receptors. In this study, the effect of two infantile phototherapy regimens, including single and intensive phototherapy was investigated on biological features of circulation endothelial progenitor cells (cEPCs), as well as on serum secretion of two important chemotactic cytokines, SDF-1 and VEGF. Sixty infants diagnosed with severe hyperbilirubinemia and exposed to phototherapy were enrolled in this study. cEPCs were isolated before and after phototherapy and then migratory, proliferative, tubulogenic, and functional properties of these cells were analyzed. Our results revealed that intensive phototherapy markedly increased the release of EPCs into the circulation, and augmented the serum concentrations of both SDF-1 and VEGF cytokines. Cell proliferation, tubulogenic, and migratory properties of cEPCs isolated and expanded from infants with intensive phototherapy were significantly improved. cEPCs from infants with intensive phototherapy also showed greater levels of acetylated low-density lipoprotein and lectin binding. Overall, our results showed that the intensive phototherapy regimen can mobilize functional EPCs into the circulation through up-regulation of serum levels of VEGF and SDF-1, indicating phototherapy as an effective modality for improvement of stem cell mobilization in the therapeutic regenerative medicine. J. Cell. Biochem. 118: 330 340, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27355423 TI - Authors' Reply. PMID- 27355424 TI - S100A12 Is Part of the Antimicrobial Network against Mycobacterium leprae in Human Macrophages. AB - Triggering antimicrobial mechanisms in macrophages infected with intracellular pathogens, such as mycobacteria, is critical to host defense against the infection. To uncover the unique and shared antimicrobial networks induced by the innate and adaptive immune systems, gene expression profiles generated by RNA sequencing (RNAseq) from human monocyte-derived macrophages (MDMs) activated with TLR2/1 ligand (TLR2/1L) or IFN-gamma were analyzed. Weighed gene correlation network analysis identified modules of genes strongly correlated with TLR2/1L or IFN-gamma that were linked by the "defense response" gene ontology term. The common TLR2/1L and IFN-gamma inducible human macrophage host defense network contained 16 antimicrobial response genes, including S100A12, which was one of the most highly induced genes by TLR2/1L. There is limited information on the role of S100A12 in infectious disease, leading us to test the hypothesis that S100A12 contributes to host defense against mycobacterial infection in humans. We show that S100A12 is sufficient to directly kill Mycobacterium tuberculosis and Mycobacterium leprae. We also demonstrate that S100A12 is required for TLR2/1L and IFN-gamma induced antimicrobial activity against M. leprae in infected macrophages. At the site of disease in leprosy, we found that S100A12 was more strongly expressed in skin lesions from tuberculoid leprosy (T-lep), the self limiting form of the disease, compared to lepromatous leprosy (L-lep), the progressive form of the disease. These data suggest that S100A12 is part of an innate and adaptive inducible antimicrobial network that contributes to host defense against mycobacteria in infected macrophages. PMID- 27355426 TI - Insomnia symptoms and suicidality in the National Comorbidity Survey - Adolescent Supplement. AB - OBJECTIVE: In this paper, we examined the relationship between insomnia symptoms and suicidality in a national sample of US adolescents, while controlling for several psychiatric disorders that are known to be associated with suicidality. Additionally, we examined whether insomnia symptoms interact to affect any suicidality variables. METHODS: Study participants were 10,123 adolescents between the ages of 13-18 from the National Comorbidity Survey - Adolescent Supplement (NCS-A). RESULTS: In bivariate analyses, all insomnia symptoms (i.e., difficulty falling asleep, difficulty staying asleep, and early morning awakening) were associated with suicide ideation, plan and attempts. In multivariate analyses, controlling for substance use, mood and anxiety disorders, as well as important covariates, difficulties falling and staying asleep had a significant relationship with 12-month and lifetime suicide variables while early morning awakening did not. CONCLUSIONS: Two of the three insomnia symptoms had a significant association with suicide thoughts and plan even after controlling for psychiatric disorders that were known to affect suicidality. Having trouble falling sleeping or staying asleep had both direct and indirect relationships (via substance use, mood and anxiety disorders) on suicidal behavior. Assessment and treatment of sleep disturbances may reduce the risk for suicidality in adolescents. PMID- 27355425 TI - Propionibacterium avidum as an Etiological Agent of Prosthetic Hip Joint Infection. AB - Propionibacterium acnes is well-established as a possible etiologic agent of prosthetic joint infections (PJIs). Other Propionibacterium spp. have occasionally been described as a cause of PJIs, but this has not previously been the case for P. avidum despite its capacity to form biofilm. We describe two patients with prosthetic hip joint infections caused by P. avidum. Both patients were primarily operated with an anteriorly curved skin incision close to the skin crease of the groin, and both were obese. Initial treatment was performed according to the DAIR procedure (debridement, antibiotics, and implant retention). In case 1, the outcome was successful, but in case 2, a loosening of the cup was present 18 months post debridement. The P. avidum isolate from case 1 and two isolates from case 2 (obtained 18 months apart) were selected for whole genome sequencing. The genome of P. avidum obtained from case 1 was approximately 60 kb larger than the genomes of the two isolates of case 2. These latter isolates were clonal with the exception of SNPs in the genome. All three strains possessed the gene cluster encoding exopolysaccharide synthesis. P. avidum has a pathogenic potential and the ability to cause clinically relevant infections, including abscess formation, in the presence of foreign bodies such as prosthetic joint components. Skin incision in close proximity to the groin or deep skin crease, such as the anteriorly curved skin incision approach, might pose a risk of PJIs by P. avidum, especially in obese patients. PMID- 27355427 TI - Cognitive flexibility correlates with gambling severity in young adults. AB - Although gambling disorder (GD) is often characterized as a problem of impulsivity, compulsivity has recently been proposed as a potentially important feature of addictive disorders. The present analysis assessed the neurocognitive and clinical relationship between compulsivity on gambling behavior. A sample of 552 non-treatment seeking gamblers age 18-29 was recruited from the community for a study on gambling in young adults. Gambling severity levels included both casual and disordered gamblers. All participants completed the Intra/Extra Dimensional Set Shift (IED) task, from which the total adjusted errors were correlated with gambling severity measures, and linear regression modeling was used to assess three error measures from the task. The present analysis found significant positive correlations between problems with cognitive flexibility and gambling severity (reflected by the number of DSM-5 criteria, gambling frequency, amount of money lost in the past year, and gambling urge/behavior severity). IED errors also showed a positive correlation with self-reported compulsive behavior scores. A significant correlation was also found between IED errors and non planning impulsivity from the BIS. Linear regression models based on total IED errors, extra-dimensional (ED) shift errors, or pre-ED shift errors indicated that these factors accounted for a significant portion of the variance noted in several variables. These findings suggest that cognitive flexibility may be an important consideration in the assessment of gamblers. Results from correlational and linear regression analyses support this possibility, but the exact contributions of both impulsivity and cognitive flexibility remain entangled. Future studies will ideally be able to assess the longitudinal relationships between gambling, compulsivity, and impulsivity, helping to clarify the relative contributions of both impulsive and compulsive features. PMID- 27355428 TI - Age-related changes in retinoic, docosahexaenoic and arachidonic acid modulation in nuclear lipid metabolism. AB - The aim of this work was to study how age-related changes could modify several enzymatic activities that regulate lipid mediator levels in nuclei from rat cerebellum and how these changes are modulated by all-trans retinoic acid (RA), docosahexaenoic acid (DHA) and arachidonic acid (AA). The higher phosphatidate phosphohydrolase activity and lower diacylglycerol lipase (DAGL) activity observed in aged animals compared with adults could augment diacylglycerol (DAG) availability in the former. Additionally, monoacylglycerol (MAG) availability could be high due to an increase in lysophosphatidate phosphohydrolase (LPAPase) activity and a decrease in monocylglycerol lipase activity. Interestingly, RA, DHA and AA were observed to modulate these enzymatic activities and this modulation was found to change in aged rats. In adult nuclei, whereas RA led to high DAG and MAG production through inhibition of their hydrolytic enzymes, DHA and AA promoted high MAG production by LPAPase and DAGL stimulation. In contrast, in aged nuclei RA caused high MAG generation whereas DHA and AA diminished it through LPAPase activity modulation. These results demonstrate that aging promotes a different nuclear lipid metabolism as well as a different type of non genomic regulation by RA, DHA and AA, which could be involved in nuclear signaling events. PMID- 27355429 TI - Structural Analysis using SHALiPE to Reveal RNA G-Quadruplex Formation in Human Precursor MicroRNA. AB - RNA G-quadruplex (rG4) structures are of fundamental importance to biology. A novel approach is introduced to detect and structurally map rG4s at single nucleotide resolution in RNAs. The approach, denoted SHALiPE, couples selective 2'-hydroxyl acylation with lithium ion-based primer extension, and identifies characteristic structural fingerprints for rG4 mapping. We apply SHALiPE to interrogate the human precursor microRNA 149, and reveal the formation of an rG4 structure in this non-coding RNA. Additional analyses support the SHALiPE results and uncover that this rG4 has a parallel topology, is thermally stable, and is conserved in mammals. An in vitro Dicer assay shows that this rG4 inhibits Dicer processing, supporting the potential role of rG4 structures in microRNA maturation and post-transcriptional regulation of mRNAs. PMID- 27355430 TI - Low-Spin Iron(III) Chiroporphyrins: (1)H NMR Studies of Cyanide and Substituted Imidazole Coordination. PMID- 27355432 TI - Cobalt-Doped FeSe2-RGO as Highly Active and Stable Electrocatalysts for Hydrogen Evolution Reactions. AB - Herein, we describe the preparation and testing of Co-doped FeSe2 hybridized with graphene (Fe1-xCoxSe2/RGO), a high-active yet stable electrocatalyst for hydrogen evolution reactions (HERs) in acidic solutions. First, we systematically analyze the composition and morphology of Fe1-xCoxSe2/RGO and attribute its excellent electrochemical performance to its unique architecture-a base of highly conductive graphene with fully exposed active edges that enhances conductivity and facilitates ion/electron transfer. Our experimental measurements indicate elevated HER activity with a moderate overpotential of ~166 mV at a hydrogen production current density of 10 mA cm(-2), a small Tafel slope of ~36 mV dec( 1), and long cycling lifespan more than 20 h. The promising results, in addition to the fact that Fe1-xCoxSe2/RGO is a high-performance, precious-metal-free electrocatalyst, pave the way for exciting opportunities in renewable hydrogen production applications. PMID- 27355431 TI - Clear Speech Variants: An Acoustic Study in Parkinson's Disease. AB - PURPOSE: The authors investigated how different variants of clear speech affect segmental and suprasegmental acoustic measures of speech in speakers with Parkinson's disease and a healthy control group. METHOD: A total of 14 participants with Parkinson's disease and 14 control participants served as speakers. Each speaker produced 18 different sentences selected from the Sentence Intelligibility Test (Yorkston & Beukelman, 1996). All speakers produced stimuli in 4 speaking conditions (habitual, clear, overenunciate, and hearing impaired). Segmental acoustic measures included vowel space area and first moment (M1) coefficient difference measures for consonant pairs. Second formant slope of diphthongs and measures of vowel and fricative durations were also obtained. Suprasegmental measures included fundamental frequency, sound pressure level, and articulation rate. RESULTS: For the majority of adjustments, all variants of clear speech instruction differed from the habitual condition. The overenunciate condition elicited the greatest magnitude of change for segmental measures (vowel space area, vowel durations) and the slowest articulation rates. The hearing impaired condition elicited the greatest fricative durations and suprasegmental adjustments (fundamental frequency, sound pressure level). CONCLUSIONS: Findings have implications for a model of speech production for healthy speakers as well as for speakers with dysarthria. Findings also suggest that particular clear speech instructions may target distinct speech subsystems. PMID- 27355434 TI - Size matters to function: Brain volume correlates with intrinsic brain activity across healthy individuals. AB - A fundamental issue in neuroscience is to understand the structural substrates of neural activities. Intrinsic brain activity has been increasingly recognized as an important functional activity mode and is tightly linked with various cognitive functions. Structurally, cognitive functions have also shown a relation with brain volume/size. Therefore, an association between intrinsic brain activities and brain volume/size can be hypothesized, and brain volume/size may impact intrinsic brain activity in human brains. The present study aimed to explicitly investigate this brain structure-function relationship using two large independent cohorts of 176 and 236 young adults. Structural-MRI was performed to estimate the brain volume, and resting-state functional-MRI was applied to extract the amplitude of low-frequency fluctuations (ALFF), an imaging measure of intrinsic brain activity. Intriguingly, our results revealed a robust linear correlation between whole-brain size and ALFF. Moreover, specific brain lobes/regions, including the frontal lobe, the left middle frontal gyrus, anterior cingulate gyrus, Rolandic operculum, and insula, also showed a reliable, positive volume-ALFF correlation in the two cohorts. These findings offer direct, empirical evidence of a strong association between brain size/volume and intrinsic brain activity, as well as provide novel insight into the structural substrates of the intrinsic brain activity of the human brain. PMID- 27355435 TI - Striatal activation reflects urgency in perceptual decision making. AB - Deciding between multiple courses of action often entails an increasing need to do something as time passes - a sense of urgency. This notion of urgency is not incorporated in standard theories of speeded decision making that assume information is accumulated until a critical fixed threshold is reached. Yet, it is hypothesized in novel theoretical models of decision making. In two experiments, we investigated the behavioral and neural evidence for an "urgency signal" in human perceptual decision making. Experiment 1 found that as the duration of the decision making process increased, participants made a choice based on less evidence for the selected option. Experiment 2 replicated this finding, and additionally found that variability in this effect across participants covaried with activation in the striatum. We conclude that individual differences in susceptibility to urgency are reflected by striatal activation. By dynamically updating a response threshold, the striatum is involved in signaling urgency in humans. PMID- 27355436 TI - Neural and behavioral correlates of selective stopping: Evidence for a different strategy adoption. AB - The present study examined the neural and behavioral correlates of selective stopping, a form of inhibition that has scarcely been investigated. The selectivity of the inhibitory process is needed when individuals have to deal with an environment filled with multiple stimuli, some of which require inhibition and some of which do not. The stimulus-selective stop-signal task has been used to explore this issue assuming that all participants interrupt their ongoing responses selectively to stop but not to ignore signals. However, recent behavioral evidence suggests that some individuals do not carry out the task as experimenters expect, since they seemed to interrupt their response non selectively to both signals. In the present study, we detected and controlled the cognitive strategy adopted by participants (n=57) when they performed a stimulus selective stop-signal task before comparing brain activation between conditions. In order to determine both the onset and the end of the response cancellation process underlying each strategy and to fully take advantage of the precise temporal resolution of event-related potentials, we used a mass univariate approach. Source localization techniques were also employed to estimate the neural underpinnings of the effects observed at the scalp level. Our results from scalp and source level analysis support the behavioral-based strategy classification. Specific effects were observed depending on the strategy adopted by participants. Thus, when contrasting successful stop versus ignore conditions, increased activation was only evident for subjects who were classified as using a strategy whereby the response interruption process was selective to stop trials. This increased activity was observed during the P3 time window in several left lateralized brain regions, including middle and inferior frontal gyri, as well as parietal and insular cortices. By contrast, in those participants who used a strategy characterized by stopping non-selectively, no activation differences between successful stop and ignore conditions were observed at the estimated time at which response interruption process occurs. Overall, results from the current study highlight the importance of controlling for the different strategies adopted by participants to perform selective stopping tasks before analyzing brain activation patterns. PMID- 27355437 TI - Bayesian electromagnetic spatio-temporal imaging of extended sources with Markov Random Field and temporal basis expansion. AB - Estimating the locations and spatial extents of brain sources poses a long standing challenge for electroencephalography and magnetoencephalography (E/MEG) source imaging. In the present work, a novel source imaging method, Bayesian Electromagnetic Spatio-Temporal Imaging of Extended Sources (BESTIES), which is built upon a Bayesian framework that determines the spatio-temporal smoothness of source activities in a fully data-driven fashion, is proposed to address this challenge. In particular, a Markov Random Field (MRF), which can precisely capture local cortical interactions, is employed to characterize the spatial smoothness of source activities, the temporal dynamics of which are modeled by a set of temporal basis functions (TBFs). Crucially, all of the unknowns in the MRF and TBF models are learned from the data. To accomplish model inference efficiently on high-resolution source spaces, a scalable algorithm is developed to approximate the posterior distribution of the source activities, which is based on the variational Bayesian inference and convex analysis. The performance of BESTIES is assessed using both simulated and actual human E/MEG data. Compared with L2-norm constrained methods, BESTIES is superior in reconstructing extended sources with less spatial diffusion and less localization error. By virtue of the MRF, BESTIES also overcomes the drawback of over-focal estimates in sparse constrained methods. PMID- 27355438 TI - SHBG, Sex Steroids, and Kyphosis in Older Men: The MrOS Study. AB - Accentuated kyphosis is associated with adverse health outcomes, including falls and fractures. Low bone density is a risk factor for hyperkyphosis, and each vertebral fracture adds roughly 4 degrees to forward spine curvature. Sex steroids, in particular low bioavailable estradiol and high sex hormone-binding globulin (SHBG), are associated with bone loss and high SHBG is associated with vertebral fractures in older men. We, therefore, hypothesized that low bioavailable estradiol and high SHBG would be associated with worse kyphosis. To test this hypothesis, we examined the cross-sectional associations between individual bioavailable sex hormones and SHBG with radiographically assessed kyphosis. Participants included 1500 men aged 65 and older from the Osteoporotic Fractures in Men (MrOS) Study, in whom baseline measures of kyphosis and sex hormones were available. Modified Cobb angle of kyphosis, calculated from T4 through T12, was assessed from supine lateral spine radiographs. Serum total estradiol and total testosterone were measured by mass spectrometry, and bioavailable sex steroids were calculated from mass action equations. After adjustment for age and other confounding variables, no association was found between bioavailable estradiol or testosterone and Cobb angle, either when kyphosis was analyzed as a continuous variable or dichotomized into highest versus lower three quartiles. In linear regression models adjusted for age and clinic site, there was a significant association between SHBG and kyphosis (parameter estimate = 0.76 per SD increase, p = 0.01). In the fully adjusted model, this association was weakened and of only borderline statistical significance (parameter estimate = 0.61 per SD, p = 0.05). Logistic models demonstrated similar findings. Although associated with bone loss, we did not demonstrate that low bioavailable estradiol translates into worse kyphosis in older men. High SHBG is associated with bone loss and vertebral fractures. Our results suggest that high SHBG may also be a risk factor for hyperkyphosis. (c) 2016 American Society for Bone and Mineral Research. PMID- 27355439 TI - Doses for post-Chernobyl epidemiological studies: are they reliable? AB - On 26 April 2016, thirty years will have elapsed since the occurrence of the Chernobyl accident, which has so far been the most severe in the history of the nuclear reactor industry. Numerous epidemiological studies were conducted to evaluate the possible health consequences of the accident. Since the credibility of the association between the radiation exposure and health outcome is highly dependent on the adequacy of the dosimetric quantities used in these studies, this paper makes an effort to overview the methods used to estimate individual doses and the associated uncertainties in the main analytical epidemiological studies (i.e. cohort or case-control) related to the Chernobyl accident. Based on the thorough analysis and comparison with other radiation studies, the authors conclude that individual doses for the Chernobyl analytical epidemiological studies have been calculated with a relatively high degree of reliability and well-characterized uncertainties, and that they compare favorably with many other non-Chernobyl studies. The major strengths of the Chernobyl studies are: (1) they are grounded on a large number of measurements, either performed on humans or made in the environment; and (2) extensive effort has been invested to evaluate the uncertainties associated with the dose estimates. Nevertheless, gaps in the methodology are identified and suggestions for the possible improvement of the current dose estimates are made. PMID- 27355440 TI - Trajectories of body mass indices and development of frailty: Evidence from the health and retirement study. AB - OBJECTIVE: To estimate trajectories of body mass index (BMI) and determine their association with incident frailty in later life. METHODS: Data come from the 2004 to 2012 waves of the Health and Retirement Study, a longitudinal survey of older adults. Analysis was restricted to respondents who were not frail at baseline (n = 10,827). BMI (kg/m(2) ) was calculated from self-reported weight and height. Incident frailty was assessed using the Frailty Index. Longitudinal growth mixture modeling was used to estimate the relationship between BMI trajectories and incident frailty over a 10-year period. RESULTS: Four trajectory classes were identified: weight gain (n = 162 [1.4%], mean final BMI = 42 kg/m(2) ), weight loss (n = 171 [1.7%], mean final BMI = 25.0 kg/m(2) ), consistent obesity (n = 640 [6.8%], mean final BMI = 34.7 kg/m(2) ), and consistent overweight (n = 9,864 [90.1%] mean final BMI = 26.0 kg/m(2) ). Cumulative incidence of frailty was 19.9%. Relative to the consistent overweight class, the weight gain class had the highest likelihood of incident frailty (odds ratio, OR: 3.61, 95% confidence interval, CI: 2.39-5.46). The consistent obesity (OR: 2.72, 95% CI: 2.06-3.58) and weight loss (OR: 2.81, 95% CI: 1.84-4.30) classes had similarly elevated risk of frailty. CONCLUSIONS: Weight change and obesity are associated with risk of frailty. PMID- 27355443 TI - Cooperative Catalysis for Selective Alcohol Oxidation with Molecular Oxygen. AB - The activation of dioxygen for selective oxidation of organic molecules is a major catalytic challenge. Inspired by the activity of nitrogen-doped carbons in electrocatalytic oxygen reduction, we combined such a carbon with metal-oxide catalysts to yield cooperative catalysts. These simple materials boost the catalytic oxidation of several alcohols, using molecular oxygen at atmospheric pressure and low temperature (80 degrees C). Cobalt and copper oxide demonstrate the highest activities. The high activity and selectivity of these catalysts arises from the cooperative action of their components, as proven by various control experiments and spectroscopic techniques. We propose that the reaction should not be viewed as occurring at an 'active site', but rather at an 'active doughnut'-the volume surrounding the base of a carbon-supported metal-oxide particle. PMID- 27355441 TI - A new function for p53 tetramerization domain in cell fate control. PMID- 27355444 TI - Isolation and characterization of bioactive compounds of Clematis gouriana Roxb. ex DC against snake venom phospholipase A2 (PLA2) computational and in vitro insights. AB - Bioactive compounds were isolated from Clematis gouriana Roxb. ex DC. The compounds were separated, characterized, the structures elucidated and submitted to the PubChem Database. The PubChem Ids SID 249494134 and SID 249494135 were tested against phospholipases A2 (PLA2) of Naja naja (Indian cobra) venom for PLA2 activity. Both the compounds showed promising inhibitory activity; computational data also substantiated the results. The two compounds underwent density functional theory calculation to observe the chemical stability and electrostatic potential profile. Molecular interactions between the compounds and PLA2 were observed at the binding pocket of the PLA2 protein. Further, this protein-ligand complexes were simulated for a timescale of 100 ns of molecular dynamics simulation. Experimental and computational results showed significant PLA2 inhibition activity. PMID- 27355446 TI - Palladium-Catalyzed Internal Nucleophile-Assisted Hydration-Olefin Insertion Cascade: Diastereoselective Synthesis of 2,3-Dihydro-1H-inden-1-ones. AB - A novel palladium-catalyzed hydration-olefin insertion cascade assisted by internal nucleophiles was developed for the synthesis of biologically significant 2,3-dihydro-1H-inden-1-ones under mild conditions. A detailed mechanistic study revealed that the assistance of the internal nucleophiles is crucial to trigger the cascade reaction via nucleopalladation of the alkyne moiety. The overall reaction is equivalent to regioselective hydration of alkynes followed by intramolecular Michael addition. This highly efficient and 100% atom-economical domino sequence afforded cis-2,3-disubstituted 2,3-dihydro-1H-inden-1-ones in excellent yields (up to 99%) with complete diastereoselectivity. PMID- 27355445 TI - Broad autism spectrum and obsessive-compulsive symptoms in adults with the fragile X premutation. AB - OBJECTIVE: Clinical observations and a limited number of research studies provide evidence that the fragile X premutation may confer risk for autism, executive dysfunction, and psychopathology. The link to autism spectrum symptoms and social cognition deficits with the premutation remains uncertain, and thus was the focus of the present investigation. METHOD: Our sample included 131 individuals, 42 men/22 women with the FMR1 premutation (mean age = 31.83 +/- 8.59 years) with a normal neurological exam, and 48 men/19 women healthy age-matched controls (mean age = 29.48 +/- 7.29 years). Individuals completed a comprehensive neuropsychological battery with additional assessments for social cognition, broad autism spectrum, and obsessive-compulsive (OC) symptoms. RESULTS: Premutation carriers self-reported higher rates of autism-related symptoms (Autism Quotient; p = .001). Among males only, premutation carriers showed more atypical social interaction (p < .001) and stereotyped behavior (p = .014) during standardized clinical examination on the Autism Diagnostic Observation Schedule (ADOS) relative to controls. Female premutation carriers reported significantly higher rates of OC symptoms compared to control females (p = .012). Molecular measures defining the expanded premutation (FMR1 CGG repeat length and/or mRNA) were significantly associated with a measure of theory of mind (Reading the Mind in the Eyes Task). CONCLUSIONS: The results of this study indicate a higher rate of broad autism spectrum symptoms in some males with the premutation and provide evidence for an obsessive-compulsive subtype in female premutation carriers. PMID- 27355448 TI - Diversity-Oriented Polymerization: One-Shot Synthesis of Library of Graft and Dendronized Polymers by Cu-Catalyzed Multicomponent Polymerization. AB - Graft and dendronized polymers have attracted much attention in the polymer community, and there have been significant efforts to develop better synthetic methods. Herein, we report the highly efficient synthesis of graft and dendronized polymers by using Cu-catalyzed multicomponent polymerization (MCP). Based on diversity-oriented synthesis, we prepared a library of various graft and dendronized polymers from combinations of three types of monomers (mono functionalized alkynes, bis-sulfonyl azides, and diamines/diols) that are bench stable and readily accessible. After reaction optimization, 54 samples of high molecular-weight graft and dendronized polymers were prepared, the MCP method allowing simultaneous manipulation of the structures of both the main chains and the side chains. Moreover, because of the severe steric hindrance of the side chains, these polymers adopted extended conformations, as shown by the large shape parameter in solution. Also, the extended morphology of the single polymer chains was directly visualized by atomic force microscopy and transmission electron microscopy in the solid state. Most importantly, this diversity-oriented polymerization became possible because of highly step-economical and efficient one-step MCP, paving the way toward the easily tunable synthesis of graft and dendronized polymers. PMID- 27355447 TI - The Cooking and Pneumonia Study (CAPS) in Malawi: Implementation of Remote Source Data Verification. AB - BACKGROUND: Source data verification (SDV) is a data monitoring procedure which compares the original records with the Case Report Form (CRF). Traditionally, on site SDV relies on monitors making multiples visits to study sites requiring extensive resources. The Cooking And Pneumonia Study (CAPS) is a 24- month village-level cluster randomized controlled trial assessing the effectiveness of an advanced cook-stove intervention in preventing pneumonia in children under five in rural Malawi (www.capstudy.org). CAPS used smartphones to capture digital images of the original records on an electronic CRF (eCRF). In the present study, descriptive statistics are used to report the experience of electronic data capture with remote SDV in a challenging research setting in rural Malawi. METHODS: At three monthly intervals, fieldworkers, who were employed by CAPS, captured pneumonia data from the original records onto the eCRF. Fieldworkers also captured digital images of the original records. Once Internet connectivity was available, the data captured on the eCRF and the digital images of the original records were uploaded to a web-based SDV application. This enabled SDV to be conducted remotely from the UK. We conducted SDV of the pneumonia data (occurrence, severity, and clinical indicators) recorded in the eCRF with the data in the digital images of the original records. RESULT: 664 episodes of pneumonia were recorded after 6 months of follow-up. Of these 664 episodes, 611 (92%) had a finding of pneumonia in the original records. All digital images of the original records were clear and legible. CONCLUSION: Electronic data capture using eCRFs on mobile technology is feasible in rural Malawi. Capturing digital images of the original records in the field allows remote SDV to be conducted efficiently and securely without requiring additional field visits. We recommend these approaches in similar settings, especially those with health endpoints. PMID- 27355449 TI - A symptom diary to assess severe premenstrual syndrome and premenstrual dysphoric disorder. AB - The differentiation between premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) has been widely discussed. PMDD is listed as a mental disorder in the DSM-5, whereas PMS is not considered as a mental disorder in any diagnostic manual. Consequently, PMS is operationalized in different ways. Keeping a symptom diary is required to diagnose PMDD but is also recommended for PMS. The aim of our study was, therefore, to operationalize PMS and PMDD within a DSM-5-based symptom diary. We developed a symptom-intensity-score (SI-score) and an interference-score (INT-score) to evaluate the symptom diary. Ninety-eight women (aged 20-45 years) completed a symptom diary over two menstrual cycles, a retrospective screening for premenstrual symptoms, and answered additional impairment questionnaires from August 2013 to August 2015. The scores revealed moderate to good reliability (Cronbach's alpha = 0.83-0.96). Convergent validity was shown by significant correlations with a retrospective screening, the Pain Disability Index, and the German PMS-Impact Questionnaire. Discriminant validity was indicated by low correlations with the Big Five Inventory-10. These scores may facilitate the evaluation of prospective symptom ratings in research and clinical practice. Future research should focus on continuing to validate the scores (e.g., in an ambulatory setting). PMID- 27355450 TI - Origin of B-Cell Neoplasms in Autoimmune Disease. AB - Autoimmune diseases (ADs) are associated with a number of B-cell neoplasms but the associations are selective in regard to the type of neoplasm and the conferred risks are variable. So far no mechanistic bases for these differential associations have been demonstrated. We speculate that developmental origin of B cells might propose a mechanistic rationale for their carcinogenic response to autoimmune stimuli and tested the hypothesis on our previous studies on the risks of B-cell neoplasms after any of 33 ADs. We found that predominantly germinal center (GC)-derived B-cells showed multiple associations with ADs: diffuse large B cell lymphoma associated with 15 ADs, follicular lymphoma with 7 ADs and Hodgkin lymphoma with 11 ADs. Notably, these neoplasms shared significant associations with 5 ADs (immune thrombocytopenic purpura, polymyositis/dermatomyositis, rheumatoid arthritis, Sjogren syndrome and systemic lupus erythematosis). By contrast, primarily non-GC neoplasms, acute lymphocytic leukemia, chronic lymphocytic leukemia and myeloma associated with 2 ADs only and mantle cell lymphoma with 1 AD. None of the neoplasms shared associated ADs. These data may suggest that autoimmune stimulation critically interferes with the rapid cell division, somatic hypermutation, class switch recombination and immunological selection of maturing B-cell in the GC and delivers damage contributing to transformation. PMID- 27355451 TI - N-Heterocyclic molecule-capped gold nanoparticles as effective antibiotics against multi-drug resistant bacteria. AB - We demonstrate that N-heterocyclic molecule-capped gold nanoparticles (Au NPs) have broad-spectrum antibacterial activity. Optimized antibacterial activity can be achieved by using different initial molar ratios (1 : 1 and 10 : 1) of N heterocyclic prodrugs and the precursor of Au NPs (HAuCl4). This work opens up new avenues for antibiotics based on Au NPs. PMID- 27355452 TI - Efficient Ni(II)2Ln(III)2 Electrocyclization Catalysts for the Synthesis of trans 4,5-Diaminocyclopent-2-enones from 2-Furaldehyde and Primary or Secondary Amines. AB - A series of heterometallic coordination clusters (CCs) [Ni(II)2Ln(III)2(L1)4Cl2(CH3CN)2] 2CH3CN [Ln = Y (1Y), Sm (1Sm), Eu (1Eu), Gd (1Gd), or Tb (1Tb)] were synthesized by the reaction of (E)-2-(2-hydroxy-3 methoxybenzylidene-amino)phenol) (H2L1) with NiCl2.6(H2O) and LnCl3.x(H2O) in the presence of Et3N at room temperature. These air-stable CCs can be obtained in very high yields from commercially available materials and are efficient catalysts for the room-temperature domino ring-opening electrocyclization synthesis of trans-4,5-diaminocyclopent-2-enones from 2-furaldehyde and primary or secondary amines under a non-inert atmosphere. Structural modification of the catalyst to achieve immobilization or photosensitivity is possible without deterioration in catalytic activity. PMID- 27355463 TI - The impact of migration on women's mental health in the postpartum period. AB - OBJECTIVE: To assess the influence of I mmigration on the psychological health of women after childbirth. METHODS: In this cross-sectional study, immigrant and Portuguese-native women delivering in the four public hospitals of the metropolitan area of Porto, Portugal, were contacted by telephone between February and December 2012 during the first postpartum month to schedule a home visit and fill in a questionnaire. Most immigrant (76.1%) and Portuguese mothers (80.0%) agreed to participate and with the visits, thus a total of 89 immigrants and 188 Portuguese women were included in the study. The questionnaire included the application of four validated scales: Mental Health Inventory-5, Edinburgh Postpartum Depression Scale, Perceived Stress Scale, and Scale of Satisfaction with Social Support. Statistical analysis included t-test and Chi-square or Fisher's test, and logistic regression models. RESULTS: Immigrants had an increased risk of postpartum depression (OR = 6.444, 95%CI 1.858-22.344), and of low satisfaction with social support (OR = 6.118, 95%CI 1.991-18.798). We did not perceive any associations between migrant state, perceived stress, and impoverished mental health. CONCLUSIONS: Immigrant mothers have increased vulnerabilities in the postpartum period, resulting in an increased risk of postpartum depression and lesser satisfaction with the received social support. PMID- 27355464 TI - Cross-Cultural adaptation of the General Functioning Scale of the Family. AB - OBJECTIVE: To describe the process of cross-cultural adaptation of the General Functioning Scale of the Family, a subscale of the McMaster Family Assessment Device, for the Brazilian population. METHODS: The General Functioning Scale of the Family was translated into Portuguese and administered to 500 guardians of children in the second grade of elementary school in public schools of Sao Goncalo, Rio de Janeiro, Southeastern Brazil. The types of equivalences investigated were: conceptual and of items, semantic, operational, and measurement. The study involved discussions with experts, translations and back translations of the instrument, and psychometric assessment. Reliability and validity studies were carried out by internal consistency testing (Cronbach's alpha), Guttman split-half correlation model, Pearson correlation coefficient, and confirmatory factor analysis. Associations between General Functioning of the Family and variables theoretically associated with the theme (father's or mother's drunkenness and violence between parents) were estimated by odds ratio. RESULTS: Semantic equivalence was between 90.0% and 100%. Cronbach's alpha ranged from 0.79 to 0.81, indicating good internal consistency of the instrument. Pearson correlation coefficient ranged between 0.303 and 0.549. Statistical association was found between the general functioning of the family score and the theoretically related variables, as well as good fit quality of the confirmatory analysis model. CONCLUSIONS: The results indicate the feasibility of administering the instrument to the Brazilian population, as it is easy to understand and a good measurement of the construct of interest. OBJETIVO: Descrever o processo de adaptacao transcultural da escala de Funcionamento Geral da Familia, subescala da McMaster Family Assessment Device, para a populacao brasileira. METODOS: A escala de Funcionamento Geral da Familia, original no idioma ingles, foi traduzida para o portugues e aplicada a 500 responsaveis de criancas do segundo ano do ensino fundamental de escolas publicas do municipio de Sao Goncalo, Rio de Janeiro. Os tipos de equivalencias investigados foram: conceitual e de itens, semantica, operacional, e mensuracao. O estudo envolveu discussao com especialistas, traducoes e retraducoes do instrumento e avaliacao psicometrica. Foi realizado estudo de confiabilidade e validade, por testagem da consistencia interna (alpha de Cronbach), da correlacao pelo metodo de split-half de Guttman e do coeficiente de correlacao de Pearson, e por analise fatorial confirmatoria. Associacoes entre Funcionamento Geral da Familia e variaveis teoricamente associadas ao tema (embriaguez do pai ou da mae e violencia entre os pais) foram analisadas por estimacao de razao de chance. RESULTADOS: A equivalencia semantica encontrada foi entre 90,0% e 100%. O alfa de Cronbach variou de 0,79 a 0,81, indicando boa consistencia interna do instrumento. O coeficiente de correlacao de Pearson oscilou entre 0,303 e 0,549. Encontrou-se associacao estatistica entre o escore de funcionamento geral da familia e as variaveis teoricamente relacionadas e constatou-se boa qualidade dos ajustes do modelo de analise confirmatoria. CONCLUSOES: Os resultados obtidos indicam a aplicabilidade do instrumento na populacao brasileira, que se mostra de facil compreensao e boa afericao do constructo de interesse. PMID- 27355465 TI - Socioeconomic and regional differences in active transportation in Brazil. AB - OBJECTIVE: To present national estimates regarding walking or cycling for commuting in Brazil and in 10 metropolitan regions. METHODS: By using data from the Health section of 2008's Pesquisa Nacional por Amostra de Domicilio (Brazil's National Household Sample Survey), we estimated how often employed people walk or cycle to work, disaggregating our results by sex, age range, education level, household monthly income per capita, urban or rural address, metropolitan regions, and macro-regions in Brazil. Furthermore, we estimated the distribution of this same frequency according to quintiles of household monthly income per capita in each metropolitan region of the country. RESULTS: A third of the employed men and women walk or cycle from home to work in Brazil. For both sexes, this share decreases as income and education levels rise, and it is higher among younger individuals, especially among those living in rural areas and in the Northeast region of the country. Depending on the metropolitan region, the practice of active transportation is two to five times more frequent among low income individuals than among high-income individuals. CONCLUSIONS: Walking or cycling to work in Brazil is most frequent among low-income individuals and the ones living in less economically developed areas. Active transportation evaluation in Brazil provides important information for public health and urban mobility policy-making. OBJETIVO: Apresentar estimativas nacionais sobre o deslocamento a pe ou de bicicleta no trajeto casa-trabalho no Brasil e em 10 de suas regioes metropolitanas. METODOS: Utilizando dados do Suplemento sobre Saude da Pesquisa Nacional por Amostra de Domicilios de 2008, estimamos a frequencia de pessoas empregadas que se deslocam a pe ou de bicicleta no trajeto casa-trabalho estratificada por sexo, e segundo faixa etaria, escolaridade, renda domiciliar per capita, residencia em area urbana ou rural, regioes metropolitanas e macrorregioes do pais. Adicionalmente, estimamos a distribuicao da mesma frequencia segundo quintos da distribuicao da renda domiciliar per capita em cada regiao metropolitana. RESULTADOS: Um terco dos homens e mulheres empregados desloca-se a pe ou de bicicleta de casa para o trabalho no Brasil. Em ambos os sexos, esta proporcao diminui com o aumento da renda e da escolaridade e e maior entre os mais jovens, entre os que residem em area rural e naqueles residentes na regiao Nordeste. A depender da regiao metropolitana, a pratica de deslocamento ativo entre os mais pobres e de duas a cinco vezes maior do que entre os mais ricos. CONCLUSOES: O deslocamento a pe ou de bicicleta para o trabalho no Brasil e mais frequente entre os mais pobres e entre pessoas que vivem em areas e regioes economicamente menos desenvolvidas. A avaliacao do deslocamento ativo no Pais traz informacoes importantes para a discussao de politicas publicas de mobilidade. PMID- 27355466 TI - Transcultural adaptation to Brazilian Portuguese and reliability of the effort reward imbalance in household and family work. AB - OBJECTIVE: To describe the steps in the transcultural adaptation of the scale in the Effort-reward imbalance model to household and family work to the Brazilian context. METHODS: We performed the translation, back-translation, and initial psychometric evaluation of the questionnaire that comprised three dimensions: (i) effort (eight items, emphasizing quantitative workload), (ii) reward (11 items that seek to capture the intrinsic value of family and household work, societal esteem, recognition from the spouse/partner, and affection from the children), and (iii) overcommitment (four items related to intrinsic effort). The scale was included in a sectional study conducted with 1,045 nursing workers. A subsample of 222 subjects answered the questionnaire for a second time, seven to 15 days thereafter. The data were collected between October 2012 and May 2013. The internal consistency of the scale was evaluated using Cronbach's alpha and test retest reliability analysis, square weighted kappa, prevalence and bias adjusted Kappa, and intraclass correlation coefficient. RESULTS: Prevalence and bias adjusted Kappa (ka) of the scale dimensions ranged from 0.80-0.83 for overcommitment, 0.78-0.90 for effort, and 0.76-0.93 for reward. In most dimensions, the values of minimum and maximum scores, average, standard deviation, and Cronbach's alpha were similar in test and retest scores. Only on societal esteem subdimension (reward) was there little variation in standard deviation (test score of 2.24 and retest score of 3.36) and in Cronbach's alpha coefficient (test score of 0.38 and retest score of 0.59). CONCLUSIONS: The Brazilian version of the scale was found to have proper reliability indices regarding time stability, which suggests adapting it to be used in population with characteristics that are similar to the one in this study. OBJETIVO: Descrever as etapas da adaptacao transcultural da escala do Effort-reward imbalance model to household and family work para o contexto brasileiro. METODOS: Efetuou-se a traducao, retrotraducao e avaliacao psicometrica inicial do instrumento composto por tres dimensoes: (i) esforco (oito itens, enfatizando a carga quantitativa de trabalho), (ii) recompensa (11 itens que buscam captar o valor intrinseco da familia e do trabalho domestico, a estima social, o reconhecimento do conjuge ou companheiro e a afeicao dos filhos) e (iii) o excesso de comprometimento (quatro itens relacionados ao esforco intrinseco). A escala foi incluida em um estudo seccional aplicado em 1.045 trabalhadoras de enfermagem. Uma subamostra de 222 participantes respondeu ao questionario pela segunda vez, com intervalo de sete a 15 dias. Os dados foram coletados entre outubro de 2012 e maio de 2013. A consistencia interna da escala foi avaliada pelo coeficiente de alpha de Cronbach e a confiabilidade teste-reteste, pelo indice kappa ponderado quadratico, pelo kappa ajustado pela prevalencia e pelo coeficiente de correlacao intraclasse. RESULTADOS: A confiabilidade ajustada pela prevalencia (ka) das dimensoes da escala variou de 0,80-0,83 para o excesso de comprometimento, 0,78-0,90 para o esforco e 0,76-0,93 para a recompensa. Na maioria das dimensoes, os valores do escore minimo e maximo, media, desvio-padrao e alpha de Cronbach no teste e no reteste foram semelhantes. Somente na subdimensao estima social (recompensa) houve pequena variacao no desvio padrao (2,24 no teste e 3,36 no reteste) e no coeficiente de alpha de Cronbach (0,38 no teste e 0,59 no reteste). CONCLUSOES: A versao brasileira da escala apresentou indices adequados de fidedignidade quanto a estabilidade temporal, o que sugere a adequacao da escala para uso em populacoes com caracteristicas semelhantes a do estudo. PMID- 27355467 TI - Trends in corrected lung cancer mortality rates in Brazil and regions. AB - OBJECTIVE: To describe the trend in cancer mortality rates in Brazil and regions before and after correction for underreporting of deaths and redistribution of ill-defined and nonspecific causes. METHODS: The study used data of deaths from lung cancer among the population aged from 30 to 69 years, notified to the Mortality Information System between 1996 and 2011, corrected for underreporting of deaths, non-registered sex and age , and causes with ill-defined or garbage codes according to sex, age, and region. Standardized rates were calculated by age for raw and corrected data. An analysis of time trend in lung cancer mortality was carried out using the regression model with autoregressive errors. RESULTS: Lung cancer in Brazil presented higher rates among men compared to women, and the South region showed the highest death risk in 1996 and 2011. Mortality showed a trend of reduction for males and increase for women. CONCLUSIONS: Lung cancer in Brazil presented different distribution patterns according to sex, with higher rates among men and a reduction in the mortality trend for men and increase for women. OBJETIVO: Descrever a tendencia da mortalidade por cancer de pulmao no Brasil e regioes, antes e apos as correcoes por sub-registro de obitos, redistribuicao de causas mal definidas e causas inespecificas. METODOS: Foram utilizados dados de obitos por cancer de pulmao da populacao de 30 a 69 anos, notificados ao Sistema de Informacao sobre Mortalidade, entre 1996 e 2011, corrigidos para sub-registro de obitos, declaracao de sexo e idade ignorados e causas com codigos mal definidos e inespecificos segundo sexo, idade e regiao. Foram calculadas taxas padronizadas por idade para dados brutos e corrigidos. Realizou-se analise da tendencia temporal da mortalidade por cancer de pulmao por meio do modelo de regressao com erros autorregressivos. RESULTADOS: O cancer de pulmao no Brasil apresentou taxas mais elevadas em homens que em mulheres e a regiao Sul foi a que apresentou maior risco de morte em 1996 e 2011. A mortalidade tendeu a reduzir para o sexo masculino e a aumentar para o sexo feminino. CONCLUSOES: O cancer de pulmao no Brasil apresenta padrao de distribuicao diferente segundo sexo, com taxas mais elevadas em homens e com reducao da tendencia de mortalidade para o sexo masculino e aumento das taxas para o sexo feminino. PMID- 27355468 TI - Emerging arboviruses and public health challenges in Brazil. AB - Environmental modification by anthropogenic actions, disordered urban growth, globalization of international exchange and climate change are some factors that help the emergence and dissemination of human infectious diseases transmitted by vectors. This review discusses the recent entry of three arboviruses in Brazil: Chikungunya, West Nile, and Zika virus, focusing on the challenges for the Country's public health. The Brazilian population is exposed to infections caused by these three arboviruses widely distributed on the national territory and associated with humans. Without effective vaccine and specific treatment, the maintainance and integration of a continuos entomological and epidemiological surveillance are important so we can set methods to control and prevent these arboviruses in the Country. RESUMO A modificacao do ambiente por acoes antropicas, o crescimento urbano desordenado, o processo de globalizacao do intercambio internacional e as mudancas climaticas sao alguns fatores que vem facilitando a emergencia e disseminacao de doencas infecciosas humanas transmitidas por vetores. Este comentario aborda a recente entrada de tres arbovirus no Brasil, Chikungunya (CHIKV), West Nile (WNV) e Zika (ZIKV), com enfoque nos desafios para a Saude Publica do Pais. Transmitidos por mosquitos vetores amplamente distribuidos no territorio nacional e associados ao homem, a populacao brasileira encontra-se exposta a infeccao por esses tres arbovirus. Na ausencia de vacina eficaz e tratamento especifico, sao importantes a manutencao e integracao de uma vigilancia entomologica e epidemiologica continua, a fim de direcionarmos metodos de controle e prevencao contra essas arboviroses no Pais. PMID- 27355469 TI - Recovery of Acid Production in Streptococcus mutans Biofilms after Short-Term Fluoride Treatment. AB - Fluoride is commonly used as an ingredient of topical oral hygiene measures. Despite the anti-acidogenic activities of fluoride against cariogenic biofilms, the recovery of the biofilms from fluoride damage is unclear. Herein, we investigated the recovery of acid production in Streptococcus mutans biofilms after short-term or during periodic 1-min fluoride treatments. For this study, 46 hour-old S. mutans biofilms were treated with fluoride (0-2,000 ppm F-) for 1-8 min and then incubated in saliva for 0-100 min. The 74-hour-old biofilms were also periodically treated with the fluoride concentration during biofilm formation (1 min/treatment). Changes in acidogenicity and viability were determined via pH drop and colony-forming unit assays, respectively. In this study, acid production after a 1-min fluoride treatment was recovered as saliva incubation time increased, which followed a linear pattern of concentration dependence (R = 0.99, R2 = 0.98). The recovery pattern was in a biphasic pattern, with an initial rapid rate followed by a second slow recovery. Furthermore, recovery from fluoride damage was retarded in a concentration-dependent manner as treatment time increased. In periodic 1-min fluoride treatments, acid production in the biofilms was not diminished during the non-fluoride treatment period; however, it was reduced in a concentration-dependent manner during the fluoride treatment period. The viability of the biofilm cells did not change, even at high fluoride concentrations. Collectively, our results suggest that brief fluoride treatment does not sustain anti-acidogenic activity against S. mutans in biofilms since the damage is recoverable with time. PMID- 27355470 TI - Physical Activity and Lipid Profile in the ELSA- Brasil Study. AB - BACKGROUND: Regular physical activity (PA) induces desirable changes in plasma levels of high- and low-density lipoproteins (HDL and LDL, respectively) and triglycerides (TG), important risk factors for cardiometabolic diseases. However, doubts whether intensity and duration have equivalent benefits remain. OBJECTIVE: To assess the association of PA intensity and duration with HDL, LDL and TG levels. METHODS: Cross-sectional study with 12,688 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline, who were not on lipid-lowering medication. After adjustment for important covariates, multiple linear regression was used to assess the association of PA intensity and duration with HDL, LDL and TG (natural logarithm) levels. RESULTS: Both moderate and vigorous PA and PA practice >= 150 min/week were significantly associated with higher HDL and lower TG levels. Vigorous PA was associated with lower LDL only on univariate analysis. After adjustments, moderate and vigorous PA increased mean HDL level by 0.89 mg/dL and 1.71 mg/dL, respectively, and reduced TG geometric mean by 0.98 mg/dL and 0.93 mg/dL, respectively. PA practice >= 150 min/week increased mean HDL level by 1.05 mg/dL, and decreased TG geometric mean by 0.98 mg/dL. CONCLUSION: Our findings reinforce the benefits of both PA parameters studied on HDL and TG levels, with a slight advantage for vigorous PA as compared to the recommendation based only on PA duration. PMID- 27355471 TI - Epidemiological Profile and Quality Indicators in Patients with Acute Coronary Syndrome in Northern Minas Gerais - Minas Telecardio 2 Project. AB - BACKGROUND: Coronary artery disease is the main cause of death in Brazil. In the Brazilian public health system, the in-hospital mortality associated with acute myocardial infarction is high. The Minas Telecardio 2 Project (Projeto Minas Telecardio 2) aims at implementing a myocardial infarction system of care in the Northern Region of Minas Gerais (MG) to decrease hospital morbidity and mortality. The aim of this study was to describe the profile of the patients with acute coronary syndrome (ACS) cared for in the period that preceded the implementation of the system of care. METHODS: Observational, prospective study of patients with ACS admitted between June 2013 and March 2014 to six emergency departments in Montes Claros, MG, and followed up until hospital discharge. RESULTS: During the study period, 593 patients were admitted with a diagnosis of ACS (mean age 63 +/- 12 years, 67.6% men), including 306 (51.6%) cases of unstable angina, 214 (36.0%) of ST-elevation myocardial infarction (STEMI), and 73 (12.3%) of non-ST-elevation myocardial infarction (NSTEMI). The total STEMI mortality was 21%, and the in-hospital mortality was 17.2%. In the STEMI patients, 46,0% underwent reperfusion therapy, including primary angioplasty in 88 and thrombolysis in six. Overall, aspirin was administered to 95.1% of the patients within 24 hours and to 93.5% at discharge, a P2Y12 inhibitor was administered to 88.7% participants within 24 hours and to 75.1% at discharge. A total of 73.1% patients received heparin within 24 hours. CONCLUSION: We observed a low reperfusion rate in patients with STEMI and limited adherence to the recommended ACS treatment in the Northern Region of MG. These observations enable opportunities to improve health care. PMID- 27355472 TI - Linking Genomo- and Pathotype: Exploiting the Zebrafish Embryo Model to Investigate the Divergent Virulence Potential among Cronobacter spp. AB - Bacteria belonging to the genus Cronobacter have been recognized as causative agents of life-threatening systemic infections primarily in premature, low-birth weight and immune-compromised neonates. Apparently not all Cronobacter species are linked to infantile infections and it has been proposed that virulence varies among strains. Whole genome comparisons and in silico analysis have proven to be powerful tools in elucidating potential virulence determinants, the presence/absence of which may explain the differential virulence behaviour of strains. However, validation of these factors has in the past been hampered by the availability of a suitable neonatal animal model. In the present study we have used zebrafish embryos to model Cronobacter infections in vivo using wild type and genetically engineered strains. Our experiments confirmed the role of the RepF1B-like plasmids as "virulence plasmids" in Cronobacter and underpinned the importantce of two putative virulence factors-cpa and zpx-in in vivo pathogenesis. We propose that by using this model in vivo infection studies are now possible on a large scale level which will boost the understanding on the virulence strategies employed by these pathogens. PMID- 27355473 TI - High tumor mast cell density is associated with longer survival of colon cancer patients. AB - BACKGROUND: Inflammatory cells and inflammatory mediators play an important role in colorectal cancer (CRC). Previous studies have shown that CRC patients with increased expression of cysteinyl leukotriene receptor 1 (CysLTR1) have a poorer prognosis, and Cysltr1-/- mice display fewer intestinal polyps. However, the role of mast cells (MCs) in colon cancer progression remains unclear. The aim of the present study was to explore the relevance of MCs in CRC. MATERIAL AND METHODS: A tissue microarray from 72 CRC patients was stained with MC anti-tryptase and chymase antibodies. Mouse colon tissue was stained with MC anti-tryptase antibody. Immunohistochemistry was used to identify MCs in patients and mice. RESULTS: Patient colon cancer tissue had in comparison with normal colon tissue a reduced number of MCs, predominantly of chymase-positive cells. Further analysis revealed that patients with a relative high MCD in their cancer tissues showed significantly longer overall survival compared to those with a low MCD [hazard ratio (HR) 0.539; 95% confidence interval (CI), 0.302-0.961]. Similar results were observed in subgroups of patients with either no distant metastasis (p = 0.004), or <75 years (p = 0.015) at time of diagnosis. Multivariate Cox analysis showed that MCD independently correlated with reduced risk of death in colon cancer patients (HR 0.380; 95% CI 0.202-0.713). Additionally, a negative correlation was found between cytoplasmic CysLTR1 expression and number of MCs. In agreement, in the CAC mouse model, Cysltr1-/- mice showed significantly higher MCs in their polyp/tumor areas compared with wild-type mice. CONCLUSION: A high MCD in cancer tissue correlated with longer patient survival independently from other risk factors for CRC. The concept that MCs have an anti-tumor effect in CRC is further supported by the findings of a negative correlation with CysLTR1 expression in patients and a high MCD in colon polyps/tumors from CysLTR1-/- mice. PMID- 27355474 TI - CDI Systems Are Stably Maintained by a Cell-Contact Mediated Surveillance Mechanism. AB - Contact-dependent growth inhibition (CDI) systems are widespread amongst Gram negative bacteria where they play important roles in inter-cellular competition and biofilm formation. CDI+ bacteria use cell-surface CdiA proteins to bind neighboring bacteria and deliver C-terminal toxin domains. CDI+ cells also express CdiI immunity proteins that specifically neutralize toxins delivered from adjacent siblings. Genomic analyses indicate that cdi loci are commonly found on plasmids and genomic islands, suggesting that these Type 5 secretion systems are spread through horizontal gene transfer. Here, we examine whether CDI toxin and immunity activities serve to stabilize mobile genetic elements using a minimal F plasmid that fails to partition properly during cell division. This F plasmid is lost from Escherichia coli populations within 50 cell generations, but is maintained in ~60% of the cells after 100 generations when the plasmid carries the cdi gene cluster from E. coli strain EC93. By contrast, the ccdAB "plasmid addiction" module normally found on F exerts only a modest stabilizing effect. cdi-dependent plasmid stabilization requires the BamA receptor for CdiA, suggesting that plasmid-free daughter cells are inhibited by siblings that retain the CDI+ plasmid. In support of this model, the CDI+ F plasmid is lost rapidly from cells that carry an additional cdiI immunity gene on a separate plasmid. These results indicate that plasmid stabilization occurs through elimination of non-immune cells arising in the population via plasmid loss. Thus, genetic stabilization reflects a strong selection for immunity to CDI. After long-term passage for more than 300 generations, CDI+ plasmids acquire mutations that increase copy number and result in 100% carriage in the population. Together, these results show that CDI stabilizes genetic elements through a toxin-mediated surveillance mechanism in which cells that lose the CDI system are detected and eliminated by their siblings. PMID- 27355475 TI - Stroke and Risks of Development and Progression of Kidney Diseases and End-Stage Renal Disease: A Nationwide Population-Based Cohort Study. AB - BACKGROUND: There is little information about the association between stroke and kidney diseases. We aimed to investigate the impact of stroke on long-term renal outcomes. METHODS: In this large population-based retrospective cohort study, we identified 100,353 subjects registered in the National Health Insurance Research Database of Taiwan from January 1, 2000, through December 31, 2012, including 33,451 stroke patients and 66,902 age-, sex- and Charlson's comorbidity index score-matched controls. RESULTS: The incidence rate of chronic kidney disease (CKD) was higher in the stroke than in the control cohort (17.5 vs. 9.06 per 1000 person-years). After multivariate adjustment, the risk of developing CKD was significantly higher in patients with stroke (adjusted hazard ratio [aHR] 1.43, 95% confidence interval [CI] 1.36-1.50, P<0.001). Subgroup analysis showed that stroke patients <50 years (aHR 1.61, P<0.001) and those with concomitant diabetes mellitus (aHR 2.12, P<0.001), hyperlipidemia (aHR 1.53, P<0.001) or gout (aHR 1.84, P<0.001) were at higher risk of incident CKD. Additionally, the risks of progression to advanced CKD and end-stage renal disease (ESRD) were significantly higher for stroke patients (aHRs, 1.22 and 1.30; P = 0.04 and P = 0.008, respectively), independent of age, sex, comorbidities and long-term medications. CONCLUSIONS: Stroke is associated with higher risks for incident CKD, decline in renal function and ESRD. Younger stroke patients, as well as those with concomitant diabetes mellitus, hyperlipidemia or gout are at greater risk for kidney diseases. PMID- 27355476 TI - Development of Patient Derived Xenograft Models of Overt Spontaneous Breast Cancer Metastasis: A Cautionary Note. AB - Several approaches are being evaluated to improve the historically limited value of studying transplanted primary tumors derived by injection of cells from established cell lines for predicting subsequent cancer therapy outcomes in patients and clinical trials. These approaches include use of genetically engineered mouse models (GEMMs) of spontaneous tumors, or patient tumor tissue derived xenografts (PDXs). Almost all such therapy studies utilizing such models involve treatment of established primary tumors. An alternative approach we have developed involves transplanted human tumor xenografts derived from established cell lines to treat mice with overt visceral metastases after primary tumor resection. The rationale is to mimic the more challenging circumstance of treating patients with late stage metastatic disease. These metastatic models entail prior in vivo selection of heritable, phenotypically stable variants with increased aggressiveness for spontaneous metastasis; they were derived by orthotopic injection of tumor cells followed by primary tumor resection and serial selection of distant spontaneous metastases, from which variant cell lines having a more aggressive heritable metastatic phenotype were established. We attempted to adopt this strategy for breast cancer PDXs. We studied five breast cancer PDXs, with the emphasis on two, called HCI-001 and HCI-002, both derived from triple negative breast cancer patients. However significant technical obstacles were encountered. These include the inherent slow growth rates of PDXs, the rarity of overt spontaneous metastases (detected in only 3 of 144 mice), very high rates of tumor regrowths at the primary tumor resection site, the failure of the few human PDX metastases isolated to manifest a more aggressive metastatic phenotype upon re-transplantation into new hosts, and the formation of metastases which were derived from de novo mouse thymomas arising in aged SCID mice that we used for the experiments. We discuss several possible strategies that may be employed to overcome these limitations. Uncovering the basis of the failure to detect a high rate of overt spontaneous distant metastases having a heritable phenotype in PDX models may reveal new insights into the biology and treatment of advanced metastatic disease. PMID- 27355477 TI - [Objective Diagnostics and Therapie of Hearing Loss Several Years after Cochlear Implant]. PMID- 27355478 TI - [Management of Complex Tympanojugular Paragangliomas]. AB - Background: Tympanojugular paraganglioma (TJP) are benign, high vascularized, local destructive tumors. Despite many studies in the literature, the management of particularly complex TJP (e. g., posterior fossa and/or carotid artery invasion) remains controversial. In the current study we present our treatment strategies for complex TJP and long-term results. Patients and methods: Between 2003 and 2013, 17 patients with TJP Fisch types C and D were treated in our institution. Primary symptoms were hearing loss, followed by facial nerve palsy and lower cranial nerve impairments. 2 patients presented with recurrent tumors. Surgical treatment after endovascular tumor embolization was performed in 14 patients. 2 patients were treated by radiation therapy. Results: Gross tumor resection was achieved in 10 patients. A temporary postoperative facial nerve palsy occurred in 2 patients and permanent postoperative vocal cord palsy in 3 patients. During long term follow-up, one patient experienced regrowth of the residual tumor. No tumor progress was observed in both patients treated with radiation therapy. Outcome assessed by Karnofsky scale showed 100% functionality in 12 patients and 90% in 5 patients. Discussion: Surgical treatment of TJP after endovascular embolization is the treatment of choice in young and healthy patients. In older patients with premorbid conditions, radiation therapy is the main treatment option and is associated with high tumor control rates. Precise preoperative staging together with individualize risk-benefit assessment and interdisciplinary treatment strategy are essential for a favorable outcome. PMID- 27355479 TI - [Percutaneous PhilTM-Embolization for Preoperative Therapy of Carotid Body Paragangliomas]. AB - Introduction: Paragangliomas are rare tumors representing a therapeutic challenge. In particular, the surgical removal may lead to life-threatening bleeding. The preoperative percutaneous embolization is an alternative that allows a high closure rate of tumor-feeding vessels in a short intervention time and thus significantly reduces intraoperative bleeding probability. Complete tumor resection is facilitated thereby. The use of a new non-adhesive liquid embolic agent is presented here. Methods: A 50-year old patient presented with 4 cm large paraganglioma of the carotid body (Shamblin II). A percutaneous embolization with 7 ml PHILTM (injectable precipitating hydrophobic liquid) was performed preoperatively. 24 h later the complete surgical resection of the tumor was performed. Results: A good distribution of the liquid embolic agent could be achieved over the entire tumor. Intraoperative resection of the tumor was much easier and faster due to low bleeding tendency over the entire surface of the tumor. Total blood loss was less than 50 ml. All adjacent nerve and arterial structures could be spared. Postoperative nerve function was normal and the patient was discharged on the 4th postoperative day. Conclusion: The combination of percutaneous embolization and surgical resection provides a safe combination in the treatment of advanced carotid body paragangliomas. The use of a novel liquid embolic agent may possibly further optimize the therapy. PMID- 27355480 TI - First Description of the Extended Spectrum-Beta-Lactamase Gene blaCTX-M-109 in Salmonella Grumpensis Strains Isolated from Neonatal Nosocomial Infections in Dakar, Senegal. AB - Nosocomial infections are very common in African hospitals, particularly in neonatal units. These infections are most often caused by bacteria such as Escherichia coli, Klebsiella spp and Staphylococcus spp. Salmonella strains are rarely involved in nosocomial infections. Here, we report the first description of S. Grumpensis in neonatal infections in Senegal. Seventeen Salmonella strains were isolated from hospitalized infants' stool samples. The following resistance phenotype was described in strains: AMXRTICRCFR FOXRCFXRCTXRCAZRIMPSATMRNARNORRCIPRTMRGMRTERSXTR. All isolates were susceptible to imipenem, 15 out of 17 produced an extended spectrum beta-lactamase (ESBL). blaOXA-1, blaSHV-1, blaTEM-1, blaCTX-M1 genes were detected in strains 8, 13, 5 and 8, respectively. blaCTX-M1 sequencing revealed the presence of blaCTX-M-109. Thirteen of the 17 Salmonella Grumpensis strains were analyzed by PFGE. These 13 isolates belonged to a single pulsotype and were genotypically identical. This is the first report of neonatal S. Grumpensis infections in Senegal, and the first report of blaCTX-M-109 in the genus Salmonella. PMID- 27355481 TI - Toward an objective and reproducible model choice via variable selection deviation. AB - Various model selection methods can be applied to seek sparse subsets of the covariates to explain the response of interest in bioinformatics. While such methods often offer very helpful predictive performances, their selections of the covariates may be much less trustworthy. Indeed, when the number of covariates is large, the selections can be highly unstable, even under a slight change of the data. This casts a serious doubt on reproducibility of the identified variables. For a sound scientific understanding of the regression relationship, methods need to be developed to find the most important covariates that have higher chance to be confirmed in future studies. Such a method based on variable selection deviation is proposed and evaluated in this work. PMID- 27355482 TI - DNA-catalyzed glycosylation using aryl glycoside donors. AB - We report the identification by in vitro selection of Zn(2+)/Mn(2+)-dependent deoxyribozymes that glycosylate the 3'-OH of a DNA oligonucleotide. Both beta and alpha anomers of aryl glycosides can be used as the glycosyl donors. Individual deoxyribozymes are each specific for a particular donor anomer. PMID- 27355483 TI - The Lectin Complement Pathway in Patients with Necrotizing Soft Tissue Infection. AB - BACKGROUND: Mannose-binding lectin (MBL) and ficolins are pattern recognition molecules (PRMs) that play an important role during infection through activation of the lectin complement pathway. We assessed whether plasma PRM levels were associated with mortality in patients with necrotizing soft tissue infection (NSTI). METHODS: We conducted a prospective, observational study over 25 months involving 135 NSTI patients with a maximum follow-up of 2.7 years. Blood samples were taken upon admission. Non-infected patients served as controls. RESULTS: PRM levels were significantly lower compared with controls. A baseline Ficolin-2 level below the median was associated with mortality at the end of follow-up (p = 0.007). No significant association was found for MBL, Ficolin-1 and Ficolin-3. A Ficolin-2 level below the median had a negative predictive value of 0.94 for 28 day mortality, and a level below the optimal cut-off was independently associated with 28-day mortality when adjusted for age, sex and chronicity [hazard ratio 6.27 (95% confidence interval 2.28-17.21), p < 0.0001], also when Simplified Acute Physiology Score II was included in the analysis [hazard ratio 3.16 (95% confidence interval 1.03-9.73), p = 0.045]. CONCLUSIONS: All PRMs were significantly lower in patients with NSTI than in controls. Only baseline Ficolin 2 was associated with short- and long-term mortality. A high baseline Ficolin-2 level indicated a 94% chance of surviving the first 28 days after admission. PMID- 27355486 TI - A more in-depth interpretation of MMPI-2 in MS patients by using Harris and Lingoes subscales. AB - Multiple Sclerosis (MS) is frequently associated with neuropsychiatric abnormalities. The aim of our study was to discriminate between psychosomatic disturbances and MS physically-related symptoms using the Harris-Lingoes subscales of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Forty six MS out-patients (35 females; mean age = 44.5); and 82 healthy volunteers (62 females; mean age = 46.5) were evaluated with MMPI-2 questionnaire. The frequency distribution of MMPI-2 clinical scales with high scores (> = 65) and the related Harris-Lingoes subscales were analyzed for both MS patients and healthy control subjects. Data analysis showed elevated scores in 47.8% of the patients mainly on MMPI-2 clinical scales 1, 2, and 3. The Harris-Lingoes subscales analysis allowed us to isolate and identify physical symptoms contributing to elevation of MMPI-2 clinical scales, reduce the occurrence of false positives (MMPI-2 clinical scales elevations mainly due to MS physical disability) and provide a more detailed description of psycho-emotional symptoms of MS patients. In conclusion, our study shows the utility of Harris-Lingoes subscales analysis when MMPI-2 is used for psychological assessment of MS patients. PMID- 27355485 TI - Sensation seeking and executive deficits in relation to alcohol, tobacco, and marijuana use frequency among university students: Value of ecologically based measures. AB - INTRODUCTION: The development of substance use and addiction has been linked to impaired executive function which relies on systems that converge in the prefrontal cortex. This study examined several measures of executive function as predictors of college student alcohol, tobacco, and marijuana use frequency and abuse. METHODS: College students (N=321) were administered the Delis-Kaplan Executive Function System (D-KEFS) test battery, the Sensation Seeking Scale V (SSSV), the Frontal Systems Behavioral Scale (FrSBe), the Perceived Stress Scale (PSS), the Michigan Alcohol Screening Test (MAST), the Fagerstrom Test of Nicotine Dependence (FTND). RESULTS: Alcohol use frequency was predicted by sensation seeking and FrSBe Disinhibition scores, but the latter only emerged as a unique predictor for binge drinking frequency. Sex and Disinhibition, Apathy and Executive Function FrSBe subscales predicted the frequency of tobacco use. FrSBe scores uniquely predicted tobacco use among daily users. Marijuana use frequency was predicted by sensation seeking, sex, perceived stress, and FrSBe Disinhibition scores, but only sensation seeking predicted daily use after controlling for other variables. FrSBe Disinhibition scores reached levels considered to be clinically significant for frequent binge drinkers and daily marijuana users. Sensation seeking emerged as the predominate predictor of the early stages of alcohol and tobacco related problems. CONCLUSIONS: These results suggest ecologically based self-report measures of frontal lobe function and sensation seeking are significant predictors of use frequency among college students and the extent of frontal dysfunction may be clinically significant among some heavy users. PMID- 27355487 TI - Investigation of the Abstraction and Dissociation Mechanism in the Nitrogen Trifluoride Channels: Combined Post-Hartree-Fock and Transition State Theory Approaches. AB - The present paper concludes our series of kinetics studies on the reactions involved in the complex mechanism of nitrogen trifluoride decomposition. Two other related reactions that, along with this mechanism, take part in an efficient boron nitride growth process are also investigated. We report results concerning two abstraction reactions, namely NF2 + N ? 2NF and NF3 + NF ? 2NF2, and two dissociations, N2F4 ? 2NF2 and N2F3 ? NF2 + NF. State-of-the-art electronic structure calculations at the CCSD(T)/cc-pVTZ level of theory were considered to determine geometries and frequencies of reactants, products, and transition states. Extrapolation of the energies to the complete basis set limit was used to obtain energies of all the species. We applied transition state theory to compute thermal rate constants including Wigner, Eckart, Bell, and deformed theory corrections in order to take tunneling effects into account. The obtained results are in good agreement with the experimental data available in the literature and are expected to provide a better phenomenological understanding of the NF3 decomposition role in the boron nitride growth for a wide range of temperature values. PMID- 27355484 TI - Dynamic Regulation of Cell Volume and Extracellular ATP of Human Erythrocytes. AB - INTRODUCTION: The peptide mastoparan 7 (MST7) triggered in human erythrocytes (rbcs) the release of ATP and swelling. Since swelling is a well-known inducer of ATP release, and extracellular (ATPe), interacting with P (purinergic) receptors, can affect cell volume (Vr), we explored the dynamic regulation between Vr and ATPe. METHODS AND TREATMENTS: We made a quantitative assessment of MST7-dependent kinetics of Vr and of [ATPe], both in the absence and presence of blockers of ATP efflux, swelling and P receptors. RESULTS: In rbcs 10 MUM MST7 promoted acute, strongly correlated changes in [ATPe] and Vr. Whereas MST7 induced increases of 10% in Vr and 190 nM in [ATPe], blocking swelling in a hyperosmotic medium + MST7 reduced [ATPe] by 40%. Pre-incubation of rbcs with 10 MUM of either carbenoxolone or probenecid, two inhibitors of the ATP conduit pannexin 1, reduced [ATPe] by 40 50% and swelling by 40-60%, while in the presence of 80 U/mL apyrase, an ATPe scavenger, cell swelling was prevented. While exposure to 10 MUM NF110, a blocker of ATP-P2X receptors mediating sodium influx, reduced [ATPe] by 48%, and swelling by 80%, incubation of cells in sodium free medium reduced swelling by 92%. ANALYSIS AND DISCUSSION: Results were analyzed by means of a mathematical model where ATPe kinetics and Vr kinetics were mutually regulated. Model dependent fit to experimental data showed that, upon MST7 exposure, ATP efflux required a fast 1960-fold increase of ATP permeability, mediated by two kinetically different conduits, both of which were activated by swelling and inactivated by time. Both experimental and theoretical results suggest that, following MST7 exposure, ATP is released via two conduits, one of which is mediated by pannexin 1. The accumulated ATPe activates P2X receptors, followed by sodium influx, resulting in cell swelling, which in turn further activates ATP release. Thus swelling and P2X receptors constitute essential components of a positive feedback loop underlying ATP-induced ATP release of rbcs. PMID- 27355489 TI - Variation in the Incidence and Magnitude of Tumor-Infiltrating Lymphocytes in Breast Cancer Subtypes: A Systematic Review. AB - Importance: The presence of tumor-infiltrating lymphocytes (TILs) is a favorable prognostic factor in breast cancer, and TILs may synergize with chemotherapy and immune checkpoint inhibitor therapy for improved clinical response. A more detailed understanding of the variation in lymphocytic infiltration in breast cancer may aid in identifying subtypes more amenable to immunomodulation. Objective: To determine the median percentage of patients with breast cancer with no, intermediate, or high levels of TIL and assess variations in lymphocytic cell subsets across breast cancer subtypes. Evidence Review: Eligible studies (PubMed, 1990-2015) analyzed tumor lymphocytic, CD8+, and FOXP3+ cellular infiltrates, and used multivariable analyses and quantitative methods for enumerating cell populations. Selection of of studies was performed in accordance with PRISMA guidelines and evaluated by 2 independent appraisers. Findings: Fifteen studies (n = 13 914) met prespecified criteria and were reviewed in December 2015. A median of 11% (range, 5%-26%) of breast cancers demonstrate lymphocyte predominant breast cancer (LPBC), with approximately 16% of cancers showing no evidence of TILs. Triple-negative (TN) breast cancers demonstrated the highest incidence of LPBC (20%; range, 4%-37%). This incidence is similar to that of breast cancers that are human epidermal growth factor 2 positive and either hormone receptor positive or negative (HER2+) at 16% (range 11%-24%). Hormone receptor positive/HER2- (HR+) breast cancer showed the lowest incidence of LPBC at 6% (range, 3%-12%). CD8+ T-cell infiltrates, indicative of type I immunity, were found in 48% of all breast cancers (range, 32%-80%) with similar levels observed in TN (60%; range, 40%-91%) and HER2+ disease (61%; range, 40%-83%). Fewer HR+ tumors demonstrated CD8+ TIL (43%; range, 30%-73%). The highest levels of FOXP3+ cells were observed in TN (70%; range, 65%-76%) and HER2+ disease (67%; range, 61%-74%). A minority of HR+ breast cancers demonstrated high levels of tumor-infiltrating FOXP3+ cells (38%; range, 35%-41%). Conclusions and Relevance: The magnitude of TIL is variable within and between breast cancer subtypes. Levels of lymphocytic subpopulations may identify breast cancers more amenable to immunomodulation and indicate additional strategies to enhance immunity in patients with low to moderate levels of TILs. PMID- 27355488 TI - Caring for the Unseen: Using Linking Social Capital to Improve Healthcare Access to Irregular Migrants in Spain. AB - PURPOSE: To describe a novel strategy using linking social capital to provide healthcare access to irregular migrants with low literacy, low numeracy, and limited cultural assimilation in a European metropolitan area. ORGANIZING CONSTRUCT: Public data show numerous shortcomings in meeting the healthcare needs of refugees and irregular migrants surging into Europe. Many irregular migrants living in European communities are unable to access information, care, or services due to lack of social capital. An overview of the problem and traditional charity strategies, including their barriers, are briefly described. A novel strategy using linking social capital to improve healthcare access of irregular migrants is explored and described. Information regarding the impact of this approach on the target population is provided. The discussion of nursing's role in employing linking social capital to care for the vulnerable is presented. CONCLUSIONS: Immigration and refugee data show that issues related to migration will continue. The novel strategy presented can be implemented by nurses with limited financial and physical resources in small community settings frequented by irregular migrants to improve health care. CLINICAL RELEVANCE: The health and well-being of irregular migrants has an impact on community health. Nurses must be aware of and consider implementing novel strategies to ensure that all community members' healthcare needs, which are a basic human right, are addressed. PMID- 27355490 TI - The Thyroid Hormone Inactivating Enzyme Type 3 Deiodinase is Present in Bactericidal Granules and the Cytoplasm of Human Neutrophils. AB - Neutrophils are important effector cells of the innate immune system. Thyroid hormone (TH) is thought to play an important role in their function. Intracellular TH levels are regulated by the deiodinating enzymes. The TH inactivating type 3 deiodinase (D3) is expressed in infiltrating murine neutrophils, and D3 knockout mice show impaired bacterial killing upon infection. This suggests that D3 plays an important role in the bacterial killing capacity of neutrophils. The mechanism behind this effect is unknown. We aimed to assess the presence of D3 in human neutrophils, and determine its subcellular localization using confocal and electron microscopy, because this could give important clues about its function in these cells. D3 appeared to be present in the cytoplasm and in myeloperoxidase containing azurophilic granules and as well as lactoferrin containing specific granules within human neutrophils. This subcellular localization did not change upon activation of the cells. D3 is observed intracellularly during neutrophil extracellular trap formation, followed by a reduction of D3 staining after release of the neutrophil extracellular traps into the extracellular space. At the transcriptional level, human neutrophils expressed additional essential elements of TH metabolism, including TH transporters and TH receptors. Here, we demonstrate the presence and subcellular location of D3 in human neutrophils for the first time and propose a model, in which D3 plays a role in the bacterial killing capacity of neutrophils either through generation of iodide for the myeloperoxidase system or through modulation of intracellular TH bioavailability. PMID- 27355491 TI - Maternally Administered Cyclic Glycine-Proline Increases Insulin-Like Growth Factor-1 Bioavailability and Novelty Recognition in Developing Offspring. AB - Cyclic glycine-proline (cGP), a metabolite of IGF-1, is an endogenous neuropeptide that improves memory in adult rats. The presence and concentrations of endogenous cGP, and its association with IGF-1 and IGF binding protein-3 (IGFBP-3) in rat milk and plasma, were evaluated during postnatal development. Maternal-infantile transfer of cGP during lactation and its efficacy on the memory of developing offspring were also investigated. Dams were gavaged with either cGP (3 mg/kg) or saline daily from postnatal days 8-22. Concentrations of cGP were measured in dams' milk, and concentrations of cGP, IGF-1, and IGFBP-3 were measured in the plasma of dams, pups, and young adults. The recognition memory, locomotor function, and anxiety-like behavior of offspring were evaluated using behavioral tests. Endogenous cGP was detected in rat milk, and its concentration was higher during peak lactation compared with late lactation. Comparisons within control groups showed low endogenous IGF-1 and IGFBP-3 and high endogenous cGP concentrations in the plasma of male pups. The reduced IGFBP 3 and increased cGP may be a response to increase the bioavailability of IGF-1 during infancy. Exogenous cGP showed oral bioavailability and effective maternal infantile transfer through milk. Maternally transferred cGP also led to improved recognition memory in the developing offspring, possibly through increased IGF-1 bioavailability, with no effect on locomotor activity and anxiety-like behavior. These results show that cGP is an essential endogenous peptide during early postnatal development as it improves the bioavailability of IGF-1 during infancy. Furthermore, maternal cGP supplementation offers an effective and natural route of administration for improving memory in the developing offspring. PMID- 27355492 TI - Seminal Plasma Induces Ovulation in Llamas in the Absence of a Copulatory Stimulus: Role of Nerve Growth Factor as an Ovulation-Inducing Factor. AB - Llamas are considered to be reflex ovulators. However, semen from these animals is reported to be rich in ovulation-inducing factor(s), one of which has been identified as nerve growth factor (NGF). These findings suggest that ovulation in llamas may be elicited by chemical signals contained in semen instead of being mediated by neural signals. The present study examines this notion. Llamas displaying a preovulatory follicle were assigned to four groups: group 1 received an intrauterine infusion (IUI) of PBS; group 2 received an IUI of seminal plasma; group 3 was mated to a male whose urethra had been surgically diverted (urethrostomized male); and group 4 was mated to an intact male. Ovulation (detected by ultrasonography) occurred only in llamas mated to an intact male or given an IUI of seminal plasma and was preceded by a surge in plasma LH levels initiated within an hour after coitus or IUI. In both ovulatory groups, circulating beta-NGF levels increased within 15 minutes after treatment, reaching values that were greater and more sustained in llamas mated with an intact male. These results demonstrate that llamas can be induced to ovulate by seminal plasma in the absence of copulation and that copulation alone cannot elicit ovulation in the absence of seminal plasma. In addition, our results implicate beta-NGF as an important mediator of seminal plasma-induced ovulation in llamas because ovulation does not occur if beta-NGF levels do not increase in the bloodstream, a change that occurs promptly after copulation with an intact male or IUI of seminal plasma. PMID- 27355493 TI - Measuring Plasma Concentrations of Ribavirin: First Report From a Quality Control Program. PMID- 27355495 TI - Advancing PMTCT Implementation Through Scientific Research: A Vital Agenda for Combating the Global AIDS Epidemic in Low- and Middle-Income Countries. PMID- 27355494 TI - Dietary Supplementation with a Low Dose of Polyphenol-Rich Grape Pomace Extract Prevents Dextran Sulfate Sodium-Induced Colitis in Rats. AB - Evidence from several epidemiological and experimental studies points to a beneficial role of dietary polyphenols in inflammatory bowel disease. In this study, we investigate the protective effect of dietary supplementation with various amounts of a polyphenol-rich grape pomace extract (GPE) on the development of dextran sulfate sodium (DSS)-induced colitis in rats. Rats were fed 21 days on a semisynthetic diet enriched with GPE (0.1%, 0.5%, and 1%), and acute colitis was induced by DSS (40 g/L in the drinking water) administration during the last 7 days. The low GPE content in the diet (0.1%) attenuated clinical signs and colon shortening and limited DSS-induced histological lesions. GPE 0.1% also attenuated the DSS-induced increase in myeloperoxidase activity and improved superoxide dismutase activity. Higher amounts of GPE in the diet induced only weak and nonsignificant protective effects. These results suggest that consumption of a low amount of polyphenol-rich GPE helps protect against colitis development. PMID- 27355496 TI - Creating Sustainable Collaborations for Implementation Science: The Case of the NIH-PEPFAR PMTCT Implementation Science Alliance. PMID- 27355497 TI - Evaluation of a Systems Analysis and Improvement Approach to Optimize Prevention of Mother-To-Child Transmission of HIV Using the Consolidated Framework for Implementation Research. AB - BACKGROUND: Despite large investments to prevent mother-to-child-transmission (PMTCT), pediatric HIV elimination goals are not on track in many countries. The Systems Analysis and Improvement Approach (SAIA) study was a cluster randomized trial to test whether a package of systems engineering tools could strengthen PMTCT programs. We sought to (1) define core and adaptable components of the SAIA intervention, and (2) explain the heterogeneity in SAIA's success between facilities. METHODS: The Consolidated Framework for Implementation Research (CFIR) guided all data collection efforts. CFIR constructs were assessed in focus group discussions and interviews with study and facility staff in 6 health facilities (1 high-performing and 1 low-performing site per country, identified by study staff) in December 2014 at the end of the intervention period. SAIA staff identified the intervention's core and adaptable components at an end-of study meeting in August 2015. Two independent analysts used CFIR constructs to code transcripts before reaching consensus. RESULTS: Flow mapping and continuous quality improvement were the core to the SAIA in all settings, whereas the PMTCT cascade analysis tool was the core in high HIV prevalence settings. Five CFIR constructs distinguished strongly between high and low performers: 2 in inner setting (networks and communication, available resources) and 3 in process (external change agents, executing, reflecting and evaluating). DISCUSSION: The CFIR is a valuable tool to categorize elements of an intervention as core versus adaptable, and to understand heterogeneity in study implementation. Future intervention studies should apply evidence-based implementation science frameworks, like the CFIR, to provide salient data to expand implementation to other settings. PMID- 27355498 TI - Patient and Provider Satisfaction With a Comprehensive Strategy to Improve Prevention of Mother-to-Child HIV Transmission Services in Rural Nigeria. AB - BACKGROUND: High mother-to-child HIV transmission rates in Nigeria are coupled with a critical shortage of trained health personnel, dearth of infrastructure, and low levels of male involvement in HIV care. This study evaluated maternal and provider satisfaction with services for prevention of mother-to-child transmission within the context of an implementation science cluster-randomized trial that included task shifting to lower-cadre workers, male engagement, point of-care CD4 cell counts, and integrated mother-infant care. METHODS: Patient and clinician satisfaction were measured at 6 control and 6 intervention sites using a 5-point Likert scale. Patient satisfaction was assessed at 6 weeks postpartum through a 22-item scale about the provider's ability to explain the health problem, time spent with the clinician, and motivation to follow prescribed treatment. Provider satisfaction was assessed through a 12-item scale about motivation, compensation, and training, with 4 additional questions about the impact of task shifting on job satisfaction to intervention arm providers. RESULTS: We measured satisfaction among 340 mothers (intervention n = 160; control n = 180) and 60 providers (intervention n = 36; control n = 24). Total patient satisfaction (maximum 5) was higher in the intervention than control arm [median (interquartile range) = 4.61 (4.22-4.79) vs. 3.84 (3.22-4.22), respectively; P < 0.001]. Provider satisfaction was generally high, and was similar between the intervention and the control arms [median (interquartile range) = 3.60 (3.37-3.91) vs. 3.50 (3.08-4.25), respectively; P = 0.69]. Provider satisfaction dropped when questions on newly acquired provider roles were included [3.47 (3.25-3.72)]. Patient and provider satisfaction were not associated with uptake of antiretroviral therapy or mother-infant retention at 6 and 12 weeks postpartum. CONCLUSIONS: Satisfaction was higher among patients at intervention sites, and provider satisfaction decreased when newly assigned roles were factored in. Task shifting should include training and supportive oversight to ensure comfort with assigned tasks. PMID- 27355499 TI - Conditional Cash Transfers to Increase Retention in PMTCT Care, Antiretroviral Adherence, and Postpartum Virological Suppression: A Randomized Controlled Trial. AB - BACKGROUND: Novel strategies are needed to increase retention in prevention of mother-to-child HIV transmission (PMTCT) services. We have recently shown that small, incremental cash transfers conditional on attending clinic resulted in increased retention along the PMTCT cascade. However, whether women who receive incentives to attend clinic visits are as adherent to antiretrovirals (ARV) as those who do not was unknown. OBJECTIVE: To determine whether HIV-infected women who received incentives to remain in care were as adherent to antiretroviral treatment and achieved the same level of viral suppression at 6 weeks postpartum as those who did not receive incentives but also remained in care. METHODS: Newly diagnosed HIV-infected women at <=32 weeks gestational age were recruited at antenatal care clinics in Kinshasa, Democratic Republic of Congo. Women were randomized in a 1:1 ratio to an intervention or control group. The intervention group received compensation ($5, plus $1 increment at each subsequent visit) conditional on attending scheduled clinic visits and accepting offered PMTCT services, whereas the control group received usual care. The proportion of participants who remained in care, were fully adherent (took all their pills at each visit) or with undetectable viral load at 6 weeks postpartum were compared across group. RESULTS: Among 433 women randomized (216 in intervention group and 217 in control group), 332 (76.7%) remained in care at 6 weeks postpartum, including 174 (80.6%) in the intervention group and 158 (72.8%) in the control group, (P = 0.04). Data on pill count were available for 297 participants (89.5%), including 156 (89.7%) and 141 (89.2%) in the intervention and control groups, respectively; 69.9% (109/156) and 68.1% (96/141) in the intervention and control groups had perfect adherence [risk difference, 0.02; 95% CI: -0.06 to 0.09]. Viral load results were available for 171 (98.3%) and 155 (98.7%) women in the intervention and control groups, respectively; 66.1% (113/171) in the intervention group and 69.7% (108/155) in the control group had an undetectable viral load (risk difference, -0.04; 95% CI: -0.14 to 0.07). Results were similar after adjusting for marital status, age, education, baseline CD4 count, viral load, gestational age, and initial ARV regimen. CONCLUSIONS: Although the provision of cash incentives to HIV-infected pregnant women led to higher retention in care at 6 weeks postpartum, among those retained in care, adherence to ARVs and virologic suppression did not differ by study group. PMID- 27355500 TI - A Protocol for a Cluster Randomized Trial on the Effect of a "feeding buddy" Program on adherence to the Prevention of Mother-To-Child-Transmission Guidelines in a Rural Area of KwaZulu-Natal, South Africa. AB - BACKGROUND: The uptake of prevention of mother-to-child-transmission (PMTCT) services has improved in South Africa but challenges remain, including adherence to the World Health Organization's (WHO) PMTCT recommendations of exclusive breastfeeding (EBF), taking antiretroviral medication (ARV); testing for early infant diagnosis; and reducing stigma. Women who practice EBF for the first 6 months are less likely to transmit HIV to their infants, yet only 7% of women EBF for 6 months in South Africa. Adherence to these recommendations remains challenging because of difficulties relating to disclosure and stigma. To address this challenge, the feeding buddy concept was developed based on studies where ARV buddies have proved effective in providing support for women living with HIV. Buddies have demonstrated a positive effect on providing emotional and social support to adhere to PMTCT guidelines. METHODS: A cluster randomized controlled trial was conducted in 16 selected randomly assigned clinics in uMhlathuze and uMlalazi districts of KwaZulu Natal, South Africa. HIV-positive pregnant women (n = 625) who intended to breastfeed were enrolled at 8 control clinics and 8 intervention clinics. The clinics were stratified on the basis of urban/rural/periurban locale and then randomly allocated to either intervention or control. In the intervention clinics, the mother chose a feeding buddy to be enrolled alongside her. Quantitative interviews with mothers and their chosen buddies took place at enrollment during pregnancy and at routine postdelivery visits at day 3 and weeks 6, 14 and 22. Women in the control clinics were followed using the same evaluation schedule. The trial evaluated the effect of a voluntary PMTCT feeding buddy program on HIV-infected women's adherence to PMTCT recommendations and stigma reduction. The proportion of women exclusively feeding at 5.5 months postpartum was the primary end-point of the trial. In-depth interviews were conducted among a convenience sample of PMTCT counselors, community caregivers, mothers, and buddies from intervention clinics and control clinics to document their overall experiences. DISCUSSION: The information collected in this study could be used to guide recommendations on how to build upon the current South Africa. PMTCT "buddy" strategy and to improve safe infant feeding. The information would be applicable to many other similar resource poor settings with poor social support structures. PMID- 27355501 TI - Mother Infant Retention for Health (MIR4Health): Study Design, Adaptations, and Challenges With PMTCT Implementation Science Research. AB - BACKGROUND: Effective retention of HIV-infected mothers and their infants is fraught with multiple challenges, resulting in loss across the continuum of prevention of mother-to-child HIV transmission (PMTCT) care and missed opportunities to offer life-saving HIV prevention and treatment. METHODS: The Mother Infant Retention for Health study is an individual-randomized study evaluating the effectiveness of active patient follow-up compared with standard of care on the combined outcome of attrition of HIV-infected women and their infants at 6 months postpartum. Lay counselors administered the active patient follow-up package of interventions, including individualized health education, use of flip charts during clinic visits, and at home, phone and short message service appointment reminders, active phone and physical tracking of patients immediately after missed clinic visits, and individualized retention and adherence support. RESULTS: Use of study visits to indicate participant progression along the PMTCT cascade highlights the nature of loss among women and infants in PMTCT care because of issues such as pregnancy complications, infant deaths, and transfer out. Delay in implementation of Option B+, unanticipated slow enrollment, a health-care worker strike, rapid HIV test kit shortages, and changes in national PMTCT guidelines necessitated several modifications to the protocol design and implementation to ensure successful completion of the study. CONCLUSIONS: Flexibility when operationalizing an implementation science study is critical in the context of the shifting landscape in a noncontrolled "real-world" setting. TRIAL REGISTRATION: Clinicaltrials.gov NCT01962220. PMID- 27355503 TI - Linkage to Care, Early Infant Diagnosis, and Perinatal Transmission Among Infants Born to HIV-Infected Nigerian Mothers: Evidence From the Healthy Beginning Initiative. AB - BACKGROUND: In 2014, Nigeria accounted for 33% of all new childhood HIV infections that occurred among the 22 Global Plan priority countries where 80% of HIV-infected women reside. Even with a vertical HIV transmission rate of 27%, only 6% of infants born to HIV-infected women in Nigeria receive early infant diagnosis (EID). This article reports rates of antiretroviral prophylaxis, EID, and mother-to-child transmission in a congregation-based Healthy Beginning Initiative (HBI) designed to increase HIV testing among pregnant women in southeast Nigeria. METHODS: This is a nested cohort study of HIV-exposed infants (HEI) within the HBI trial originally designed as a 2-arm cluster randomized trial. HIV-infected mothers and infants were followed between January 2013 and August 2014. RESULTS: Across both arms of the study, 72 HIV-infected women delivered 69 live infants (1 set of twins) and 4 had miscarriages. Of the 69 live born HEI, HIV status was known for 71% (49/69), 16% (11/69) died before sample collection, and 13% (9/69) were lost to follow-up. Complete information was available for 84% of HEI (58/69), of which 64% (37/58) received antiretroviral prophylaxis. Among the 49 infants tested for HIV, 88% (43/49) received EID within 2 months and 12% (6/49) received antibody testing after 18 months. The mother-to child transmission rate was 8.2% (4/49). CONCLUSIONS: EID was higher and HIV transmission rate was lower among the HBI participants compared to reported rates in 2014. However, further progress is needed to achieve goals of elimination of infant HIV infection. PMID- 27355502 TI - Cost-Effectiveness of Pre-exposure HIV Prophylaxis During Pregnancy and Breastfeeding in Sub-Saharan Africa. AB - INTRODUCTION: Antiretroviral pre-exposure prophylaxis (PrEP) for the prevention of HIV acquisition is cost-effective when delivered to those at substantial risk. Despite a high incidence of HIV infection among pregnant and breastfeeding women in sub-Saharan Africa (SSA), a theoretical increased risk of preterm birth on PrEP could outweigh the HIV prevention benefit. METHODS: We developed a decision analytic model to evaluate a strategy of daily oral PrEP during pregnancy and breastfeeding in SSA. We approached the analysis from a health care system perspective across a lifetime time horizon. Model inputs were derived from existing literature and local sources. The incremental cost-effectiveness ratio (ICER) of PrEP versus no PrEP was calculated in 2015 U.S. dollars per disability adjusted life year (DALY) averted. We evaluated the effect of uncertainty in baseline estimates through one-way and probabilistic sensitivity analyses. RESULTS: PrEP administered to pregnant and breastfeeding women in SSA was cost effective. In a base case of 10,000 women, the administration of PrEP averted 381 HIV infections but resulted in 779 more preterm births. PrEP was more costly per person ($450 versus $117), but resulted in fewer disability-adjusted life years (DALYs) (3.15 versus 3.49). The incremental cost-effectiveness ratio of $965/DALY averted was below the recommended regional threshold for cost-effectiveness of $6462/DALY. Probabilistic sensitivity analyses demonstrated robustness of the model. CONCLUSIONS: Providing PrEP to pregnant and breastfeeding women in SSA is likely cost-effective, although more data are needed about adherence and safety. For populations at high risk of HIV acquisition, PrEP may be considered as part of a broader combination HIV prevention strategy. PMID- 27355505 TI - Home-Based HIV Testing Among Pregnant Couples Increases Partner Testing and Identification of Serodiscordant Partnerships. AB - INTRODUCTION: Male partner HIV testing has been recognized as an important component of prevention of mother-to-child HIV transmission. Scheduled home-based couple HIV testing may be an effective strategy to reach men. METHODS: Women attending their first antenatal visit at Kisumu County Hospital in Kenya were randomized to home-based education and HIV testing within 2 weeks of enrollment (HOPE) or to written invitations for male partners to attend clinic (INVITE). Male partner HIV testing and maternal child health outcomes were compared at 6 months postpartum. RESULTS: Of 1101 women screened, 620 were eligible and 601 were randomized to HOPE (n = 306) or INVITE (n = 295). At 6 months postpartum, male partners were more than twice as likely [relative risk (RR) = 2.10; 95% CI (CI): 1.81 to 2.42] to have been HIV tested in the HOPE arm [233 (87%)] compared with the INVITE arm [108 (39%)]. Couples in the HOPE arm [192 (77%)] were 3 times as likely (RR = 3.17; 95% CI: 2.53 to 3.98) to have been tested as a couple as the INVITE arm [62 (24%)] and women in the HOPE arm [217 (88%)] were also twice as likely (RR = 2.27; 95% CI: 1.93 to 2.67) to know their partner's HIV status as the INVITE arm [98 (39%)]. More serodiscordant couples were identified in the HOPE arm [33 (13%)] than in the INVITE arm [10 (4%)] (RR = 3.38; 95% CI: 1.70 to 6.71). Maternal child health outcomes of facility delivery, postpartum family planning, and exclusive breastfeeding did not vary by arm. CONCLUSIONS: Home based HIV testing for pregnant couples resulted in higher uptake of male partner and couple testing, as well as higher rates of HIV status disclosure and identification of serodiscordant couples. However, the intervention did not result in higher uptake of maternal child health outcomes, because facility delivery and postpartum family planning were high in both arms, whereas exclusive breastfeeding was low. The HOPE intervention was successful at its primary aim to increase HIV testing and disclosure among pregnant couples and was able to find more serodiscordant couples compared with the invitation-only strategy. TRIAL REGISTRATION: Clinicaltrials.gov registry: NCT01784783. PMID- 27355504 TI - Identifying and Prioritizing Implementation Barriers, Gaps, and Strategies Through the Nigeria Implementation Science Alliance: Getting to Zero in the Prevention of Mother-to-Child Transmission of HIV. AB - BACKGROUND: In 2013, Nigeria accounted for 15% of the 1.3 million pregnant women living with HIV in sub-Saharan Africa and 26% of new infections among children worldwide. Despite this, less than 20% of pregnant women in Nigeria received an HIV test during pregnancy, and only 23% of HIV-infected pregnant women received appropriate intervention following HIV diagnosis. This article reports findings from 2 structured group exercises conducted at the first Nigeria Implementation Science Alliance Conference to identify (1) barriers and research gaps related to prevention of mother-to-child transmission (PMTCT) and (2) potential strategies and interventions that could address PMTCT challenges. METHODS: Two 1-hour structured group exercises were conducted with 10 groups of 14-15 individuals (n = 145), who were asked to brainstorm barriers and strategies and to rank their top 3 in each category. Data analysis eliminated duplicate responses and categorized each of the priorities along the HIV care continuum: HIV diagnosis, linkage to care, or retention in care. RESULTS: Participating stakeholders identified 20 unique barriers and research gaps related to PMTCT across the HIV continuum. Twenty-five unique interventions and implementation strategies were identified. Similar to the barriers and research gaps, these interventions and strategies were distributed across the HIV care continuum. CONCLUSIONS: The barriers and strategies identified in this study represent important pathways to progress addressing MTCT. The deliberate involvement of state and federal policy makers, program implementers, and researchers helps ensure that they are relevant and actionable. PMID- 27355506 TI - Modeling the Cost-Effectiveness of Home-Based HIV Testing and Education (HOPE) for Pregnant Women and Their Male Partners in Nyanza Province, Kenya. AB - INTRODUCTION: Women in sub-Saharan Africa face a 2-fold higher risk of HIV acquisition during pregnancy and postpartum and the majority do not know the HIV status of their male partner. Home-based couple HIV testing for pregnant women can reduce HIV transmission to women and infants while increasing antiretroviral therapy (ART) coverage in men. However, the cost-effectiveness of this program has not been evaluated. METHODS: We modeled the health and economic impact of implementing a home-based partner education and HIV testing (HOPE) intervention for pregnant women and their male partners in a region of Western Kenya (formally Nyanza Province). We used data from the HOPE randomized clinical trial conducted in Kisumu, Kenya, to parameterize a mathematical model of HIV transmission. We conducted an in-country microcosting of the HOPE intervention (payer perspective) to estimate program costs as well as a lower cost scenario of task-shifting to community health workers. RESULTS: The incremental cost of adding the HOPE intervention to standard antenatal care was $31-37 and $14-16 USD per couple tested with program and task-shifting costs, respectively. At 60% coverage of male partners, HOPE was projected to avert 6987 HIV infections and 2603 deaths in Nyanza province over 10 years with an incremental cost-effectiveness ratio (ICER) of $886 and $615 per disability-adjusted life year averted for the program and task-shifting scenario, respectively. ICERs were robust to changes in intervention coverage, effectiveness, and ART initiation and dropout rates. CONCLUSIONS: The HOPE intervention can moderately decrease HIV-associated morbidity and mortality by increasing ART coverage in male partners of pregnant women. ICERs fall below Kenya's per capita gross domestic product ($1358) and are therefore considered cost-effective. Task-shifting to community health workers can increase intervention affordability and feasibility. PMID- 27355508 TI - Optimizing Antiretroviral Therapy (ART) for Maternal and Child Health (MCH): Rationale and Design of the MCH-ART Study. AB - BACKGROUND: Prevention of mother-to-child transmission of HIV implementation faces significant challenges globally, particularly in the context of universal lifelong antiretroviral therapy (ART) for all HIV-infected pregnant women. METHODS: We describe the rationale and methods of the Maternal and Child Health Antiretroviral Therapy (MCH-ART) study, an implementation science project examining strategies for providing HIV care and treatment to HIV-infected women who initiate ART during pregnancy and their HIV-exposed infants. RESULTS: MCH-ART is composed of 3 interrelated study designs across the antenatal and postnatal periods. Phase 1 is a cross-sectional evaluation of consecutive HIV-infected pregnant women seeking antenatal care; phase 2 is an observational cohort of all women from phase 1 who are eligible for initiation of ART following local guidelines; and phase 3 is a randomized trial of strategies for delivering ART to breastfeeding women from phase 2 during the postpartum period. During each phase, a set of study measurement visits is carried out separately from antenatal care and ART services; a maximum of 9 visits takes place from the beginning of antenatal care through 12 months postpartum. In parallel, in-depth interviews are used to examine issues of ART adherence and retention qualitatively, and costs and cost-effectiveness of models of care are examined. Separate substudies examine health outcomes in HIV-uninfected women and their HIV-unexposed infants, and the role of the adherence club model for long-term adherence and retention. DISCUSSION: Combining observational and experimental components, the MCH-ART study presents a novel approach to understand and optimize ART delivery for MCH. PMID- 27355507 TI - Option B+ in Mozambique: Formative Research Findings for the Design of a Facility Level Clustered Randomized Controlled Trial to Improve ART Retention in Antenatal Care. AB - INTRODUCTION: With the rollout of "Option B+" in Mozambique in 2013, initial data indicated major challenges to early retention in antiretroviral therapy (ART) among HIV-positive pregnant women. We sought to develop and test a pilot intervention in 6 large public clinics in central Mozambique to improve retention of mothers starting ART in antenatal care. The results from the formative research from this study described here were used to design the intervention. METHODS: The research was initiated in early 2013 and completed in early 2014 in each of the 6 study clinics and consisted of (1) patient flow mapping and measurement of retention through collection of health systems data from antenatal care registries, pharmacy registries, ART clinic databases, (2) workforce assessment and measurement of patient waiting times, and (3) patient and worker individual interviews and focus groups. RESULTS: Coverage of HIV testing and ART initiation were over 90% at all sites, but retention at 30-, 60-, and 90-day pharmacy refill visits was very low ranging from only 5% at 1 site to 30% returning at 90 days. These data revealed major systemic bottlenecks that contributed to poor adherence and retention in the first month after ART initiation. Long wait times, short consultations, and poor counseling were identified as barriers. CONCLUSIONS: Based on these findings, we designed an intervention with these components: (1) workflow modification to redefine nurse tasks, shift tasks to community health workers, and enhance patient tracking and (2) an adherence and retention package to systematize active patient follow-up, ensure home visits by community health workers, use text messaging, and intensify counseling by health staff. This intervention is currently under evaluation using a stepped wedge design. PMID- 27355509 TI - Point-of-Care Virologic Testing to Improve Outcomes of HIV-Infected Children in Zambia: A Clinical Trial Protocol. AB - INTRODUCTION: In the absence of early infant diagnosis (EID) and immediate antiretroviral therapy (ART), some 50% of untreated HIV-infected infants die before age 2. Conventional EID requires sophisticated instruments that are typically placed in centralized or reference laboratories. In low-resource settings, centralized systems often lead to result turnaround times of several months, long delays in diagnosis, and adverse outcomes for HIV-infected children. Our clinical trial tests the effectiveness of a new point-of-care (POC) diagnostic technology to identify HIV-infected infants and start providing them life-saving ART as soon as possible. METHODS AND DESIGN: The study uses a randomized, controlled design to test whether the Alere q platform for HIV DNA polymerase chain reaction (PCR) testing improves outcomes of HIV-infected children in Zambia. We aim to enroll 2867 HIV-exposed infants aged 4-12 weeks and to follow those who are HIV infected for 12 months as they receive HIV care at 6 public health facilities in Lusaka. The trial's primary endpoint is the proportion of HIV-infected infants in each study arm who start ART and remain alive, in care, and virally suppressed 12 months after their diagnostic blood draw. DISCUSSION: Our trial will provide evidence for the incremental benefit of implementing a POC EID strategy in low-resource settings where only off-site PCR services are currently available. The results will be useful in guiding future decisions regarding investments in POC virologic testing as part of overall pediatric AIDS mitigation strategies in sub-Saharan Africa. TRIAL REGISTRATION: clinicaltrials.gov NCT02682810. PMID- 27355510 TI - Concept Mapping of PMTCT Implementation Challenges and Solutions Across 6 sub Saharan African Countries in the NIH-PEPFAR PMTCT Implementation Science Alliance. AB - OBJECTIVE: Although tremendous gains have been made to reduce mother-to-child HIV transmission (MTCT) globally, evidence-based practice implementation remains inconsistent in sub-Saharan Africa. We sought to identify the key domains for effective prevention of MTCT (PMTCT) implementation, using a participatory mixed methods approach. METHODS: Participants were members of the NIH-PEPFAR PMTCT Implementation Science Alliance (ISA), a platform of researchers, public-health practitioners, policymakers, and donors supported through NIH/PEPFAR. We used concept mapping to identify priority areas for PMTCT implementation science. Participants responded to the focus question: "In your experience, what factors have facilitated or hindered implementation of PMTCT interventions?" Responses were consolidated into discrete statements, grouped together based on similarity, and rated for importance, changeability, and extent to which ISA participation enhanced the capacity to influence/change the factor. RESULTS: Using multidimensional scaling and cluster analysis, we identified 12 key domains of PMTCT implementation. Two domains (Governmental Commitment and Data Measurement & Collection) were consistently ranked at or near the top for overall importance, perceived changeability, and enhanced ability to address through ISA participation. DISCUSSION: Through a stakeholder-based, participatory approach, we identified key domains for that should be considered for future PMTCT implementation research in sub-Saharan Africa. PMID- 27355511 TI - Frequent Use of the IgA Isotype in Human B Cells Encoding Potent Norovirus Specific Monoclonal Antibodies That Block HBGA Binding. AB - Noroviruses (NoV) are the most common cause of non-bacterial acute gastroenteritis and cause local outbreaks of illness, especially in confined situations. Despite being identified four decades ago, the correlates of protection against norovirus gastroenteritis are still being elucidated. Recent studies have shown an association of protection with NoV-specific serum histo blood group antigen-blocking antibody and with serum IgA in patients vaccinated with NoV VLPs. Here, we describe the isolation and characterization of human monoclonal IgG and IgA antibodies against a GI.I NoV, Norwalk virus (NV). A higher proportion of the IgA antibodies blocked NV VLP binding to glycans than did IgG antibodies. We generated isotype-switched variants of IgG and IgA antibodies to study the effects of the constant domain on blocking and binding activities. The IgA form of antibodies appears to be more potent than the IgG form in blocking norovirus binding to histo-blood group antigens. These studies suggest a unique role for IgA antibodies in protection from NoV infections by blocking attachment to cell receptors. PMID- 27355512 TI - Pharmacodynamic studies of voriconazole: informing the clinical management of invasive fungal infections. AB - INTRODUCTION: Voriconazole is a broad-spectrum antifungal agent commonly used to treat invasive fungal infections (IFI), including aspergillosis, candidiasis, Scedosporium infection, and Fusarium infection. IFI often occur in immunocompromised patients, leading to increased morbidity and mortality. AREAS COVERED: The objective of this review is to summarize the pharmacodynamic properties of voriconazole and to provide considerations for potential optimal dosing strategies. Studies have demonstrated superior clinical response when an AUC/MIC >25 or Cmin/MIC >1 is attained in adult patients, correlating to a trough concentration range as narrow as 2-4.5 mg/L; however, these targets are poorly established in the pediatric population. Topics in this discussion include voriconazole use in multiple age groups, predisposing patient factors for IFI, and considerations for clinicians managing IFI. Expert commentary: The relationship between voriconazole dosing and exposure is not well defined due to the large inter- and intra-subject variability. Development of comprehensive decision support tools for individualizing dosing, particularly in children who require higher dosing, will help to increase the probability of achieving therapeutic efficacy and decrease sub-therapeutic dosing and adverse events. PMID- 27355514 TI - Antimuscarinic Bronchodilator Response Retained after Bronchoscopic Vagal Denervation in Chronic Obstructive Pulmonary Disease Patients. PMID- 27355513 TI - Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors. AB - We investigate the associations of three established plasma biomarkers in the context of HIV and treatment-related variables including a comprehensive cardiovascular disease risk assessment, within a large ambulatory HIV cohort. Patients were recruited in 2010 to form the Royal Perth Hospital HIV/CVD risk cohort. Plasma sCD14, sCD163 and CXCL10 levels were measured in 475 consecutive patients with documented CVD risk (age, ethnicity, gender, smoking, blood pressure, BMI, fasting metabolic profile) and HIV treatment history including immunological/virological outcomes. The biomarkers assessed showed distinct associations with virological response: CXCL10 strongly correlated with HIV-1 RNA (p<0.001), sCD163 was significantly reduced among 'aviraemic' patients only (p = 0.02), while sCD14 was unaffected by virological status under 10,000 copies/mL (p>0.2). Associations between higher sCD163 and protease inhibitor therapy (p = 0.05) and lower sCD14 with integrase inhibitor therapy (p = 0.02) were observed. Levels of sCD163 were also associated with CVD risk factors (age, ethnicity, HDL, BMI), with a favourable influence of Framingham score <10% (p = 0.04). Soluble CD14 levels were higher among smokers (p = 0.002), with no effect of other CVD risk factors, except age (p = 0.045). Our findings confirm CXCL10, sCD163 and sCD14 have distinct associations with different aspects of HIV infection and treatment. Levels of CXCL10 correlated with routinely monitored variables, sCD163 levels reflect a deeper level of virological suppression and influence of CVD risk factors, while sCD14 levels were not associated with routinely monitored variables, with evidence of specific effects of smoking and integrase inhibitor therapy warranting further investigation. PMID- 27355515 TI - Natural Tripeptide-Based Inhibitor of Multifaceted Amyloid beta Toxicity. AB - Accumulation of amyloid beta (Abeta) peptide and its aggregates in the human brain is considered as one of the hallmarks of Alzheimer's disease (AD). The polymorphic oligomers and fully grown fibrillar aggregates of Abeta exhibit different levels of neuronal toxicity. Moreover, aggregation of Abeta in the presence of redox-active metal ions like Cu(2+) is responsible for the additional trait of cellular toxicity induced by the generation of reactive oxygen species (ROS). Herein, a multifunctional peptidomimetic inhibitor (P6) has been presented, based on a naturally occurring metal chelating tripeptide (GHK) and the inhibitor of Abeta aggregation. It was shown by employing various biophysical studies that P6 interact with Abeta and prevent the formation of toxic Abeta forms like oligomeric species and fibrillar aggregates. Further, P6 successfully sequestered Cu(2+) from the Abeta-Cu(2+) complex and maintained it in a redox dormant state to prevent the generation of ROS. P6 inhibited membrane disruption by Abeta oligomers and efficiently prevented DNA damage caused by the Abeta Cu(2+) complex. PC12 cells were rescued from multifaceted Abeta toxicity when treated with P6, and the amount of ROS generated in cells was reduced. These attributes make P6 a potential therapeutic candidate to ameliorate the multifaceted Abeta toxicity in AD. PMID- 27355517 TI - Rapid Access to Orthogonally Functionalized Naphthalenes: Application to the Total Synthesis of the Anticancer Agent Chartarin. AB - We report the synthesis of orthogonally functionalized naphthalenes from simple, commercially available indanones in four steps. The developed method proceeds through a two-step process that features a thermally induced fragmentation of a cyclopropane indanone with simultaneous 1,2-chloride shift. Migration of the chloride substituent occurs in a regioselective manner to preferentially afford the para-chloronaphthol substitution pattern. The obtained naphthols are versatile building blocks that can be selectively modified and used for the efficient construction of biologically active molecules. This has enabled the total synthesis of the potent anticancer natural product chartarin through a highly convergent retrosynthetic bond disconnection. PMID- 27355516 TI - Inhibition of Cdc42 and Rac1 activities in pheochromocytoma, the adrenal medulla tumor. AB - Altered Rho GTPase signaling has been linked to many types of cancer. As many small G proteins, Rho GTPases cycle between an active and inactive state thanks to specific regulators that catalyze exchange of GDP into GTP (Rho-GEF) or hydrolysis of GTP into GDP (Rho-GAP). Recent studies have shown that alteration takes place either at the level of Rho proteins themselves (expression levels, point mutations) or at the level of their regulators, mostly RhoGEFs and RhoGAPs. Most reports describe Rho GTPases gain of function that may participate to the tumorigenesis processes. In contrast, we have recently reported that decreased activities of Cdc42 and Rac1 as well as decreased expression of 2 Rho-GEFs, FARP1 and ARHGEF1, correlate with pheochromocytomas, a tumor developing in the medulla of the adrenal gland (Croise et al., Endocrine Related Cancer, 2016). Here we highlight the major evidence and further study the correlation between Rho GTPases activities and expression levels of ARHGEF1 and FARP1. Finally we also discuss how the decrease of Cdc42 and Rac1 activities may help human pheochromocytomas to develop and comment the possible relationship between FARP1, ARHGEF1 and the 2 Rho GTPases Cdc42 and Rac1 in tumorigenesis. PMID- 27355518 TI - Denitrification and dilution along fracture flowpaths influence the recovery of a bedrock aquifer from nitrate contamination. AB - In 2000, elevated nitrate concentrations ranging from 12 to 34mg/L NO3N were discovered in groundwater from numerous domestic bedrock wells adjacent to a large dairy farm in central Vermont. Long-term plots and contours of nitrate vs. time for bedrock wells showed "little/no", "moderate", and "large" change patterns that were spatially separable. The metasedimentary bedrock aquifer is strongly anisotropic and groundwater flow is controlled by fractures, bedding/foliation, and basins and ridges in the bedrock surface. Integration of the nitrate concentration vs. time data and the physical and chemical aquifer characterization suggest two nitrate sources: a point source emanating from a waste ravine and a non-point source that encompasses the surrounding fields. Once removed, the point source of NO3 (manure deposited in a ravine) was exhausted and NO3 dropped from 34mg/L to <10mg/L after ~10years; however, persistence of NO3 in the 3 to 8mg/L range (background) reflects the long term flux of nitrates from nutrients applied to the farm fields surrounding the ravine over the years predating and including this study. Inferred groundwater flow rates from the waste ravine to either moderate change wells in basin 2 or to the shallow bedrock zone beneath the large change wells are 0.05m/day, well within published bedrock aquifer flow rates. Enrichment of (15)N and (18)O in nitrate is consistent with lithotrophic denitrification of NO3 in the presence of dissolved Mn and Fe. Once the ravine point-source was removed, denitrification and dilution collectively were responsible for the down-gradient decrease of nitrate in this bedrock aquifer. Denitrification was most influential when NO3N was >10mg/L. Our multidisciplinary methods of aquifer characterization are applicable to groundwater contamination in any complexly-deformed and metamorphosed bedrock aquifer. PMID- 27355519 TI - Presence and select determinants of organophosphate flame retardants in public swimming pools. AB - The occurrence of five organophosphate flame retardants (PFRs) consisting of tributyl phosphate (TNBP), tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2 propyl) phosphate (TCIPP), tris(1.3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) in swimming pools were investigated. Fifteen chlorinated public swimming pools were sampled, including indoor pools, outdoor pools and spa pools. The analyses were carried out using isotope dilution gas chromatography tandem mass spectrometry. All five PFRs were detected in swimming pool waters with concentrations ranging from 5-27ng/L (TNBP), 7-293ng/L (TCEP), 62-1180ng/L (TCIPP), 10-670ng/L (TDCIPP) and 8-132ng/L (TPHP). The concentrations of PFRs were generally higher in indoor swimming pools compared to outdoor swimming pools. In municipal water supplies, used to fill the swimming pools in three of the sampling locations, the five PFRs were all below the limit of quantifications, eliminating this as the source. Potential leaching of PFRs from commonly used swimming equipment, including newly purchased kickboards and swimsuits was investigated. These experiments revealed that PFRs leached from swimsuits, and may be a source of PFRs in swimming pools. A quantitative risk assessment revealed that the health risk to PFRs via swimming pools was generally low and below commonly applied health risk benchmarks. PMID- 27355520 TI - Heavy metals in drinking water: Occurrences, implications, and future needs in developing countries. AB - Heavy metals in drinking water pose a threat to human health. Populations are exposed to heavy metals primarily through water consumption, but few heavy metals can bioaccumulate in the human body (e.g., in lipids and the gastrointestinal system) and may induce cancer and other risks. To date, few thousand publications have reported various aspects of heavy metals in drinking water, including the types and quantities of metals in drinking water, their sources, factors affecting their concentrations at exposure points, human exposure, potential risks, and their removal from drinking water. Many developing countries are faced with the challenge of reducing human exposure to heavy metals, mainly due to their limited economic capacities to use advanced technologies for heavy metal removal. This paper aims to review the state of research on heavy metals in drinking water in developing countries; understand their types and variability, sources, exposure, possible health effects, and removal; and analyze the factors contributing to heavy metals in drinking water. This study identifies the current challenges in developing countries, and future research needs to reduce the levels of heavy metals in drinking water. PMID- 27355521 TI - Absence of low energy magnetic spin-fluctuations in isovalently and aliovalently doped LaCo2B2 superconducting compounds. AB - Magnetization, resistivity and (11)B, (59)Co NMR measurements have been performed on the Pauli paramagnet [Formula: see text], and the superconductors [Formula: see text] ([Formula: see text] K) and [Formula: see text] ([Formula: see text] K). The site selective NMR experiment reveals the multiband nature of the Fermi surface in these systems. The temperature independent Knight shift and 1/T 1 T clearly indicate the absence of correlated low energy magnetic spin-fluctuations in the normal state, which is in contrast to other Fe-based pnictides. The density of states (DOS) of Co 3d electrons has been enhanced in superconducting [Formula: see text] and [Formula: see text] with respect to the non superconducting reference compound [Formula: see text]. The occurrence of superconductivity is related to the DOS enhancement. PMID- 27355522 TI - Integrating Display and Delivery Functionality with a Cell Penetrating Peptide Mimic as a Scaffold for Intracellular Multivalent Multitargeting. AB - The construction of a multivalent ligand is an effective way to increase affinity and selectivity toward biomolecular targets with multiple-ligand binding sites. Adopting this strategy, we used a known cell-penetrating peptide (CPP) mimic as a scaffold to develop a series of multivalent ligand constructs that bind to the expanded dCTG (CTG(exp)) and rCUG nucleotide repeats (CUG(exp)) known to cause myotonic dystrophy type I (DM1), an incurable neuromuscular disease. By assembling this polyvalent construct, the hydrophobic ligands are solubilized and delivered into cell nuclei, and their enhanced binding affinity leads to the inhibition of ribonuclear foci formation and a reversal of splicing defects, all at low concentrations. Some of the multivalent ligands are shown to inhibit selectively the in vitro transcription of (CTG.CAG)74, to reduce the concentration of the toxic CUG RNA in DM1 model cells, and to show phenotypic improvement in vivo in a Drosophila model of DM1. This strategy may be useful in drug design for other trinucleotide repeat disorders and more broadly for intracellular multivalent targeting. PMID- 27355523 TI - High-Throughput Screening and Optimization of Binary Quantum Dots Cosensitized Solar Cell. AB - Quantum dots (QDs) are considered as the alternative of dye sensitizers for solar cells. However, interfacial construction and evaluation of photocatalytic nanomaterials still remains challenge through the conventional methodology involving demo devices. We propose here a high-throughput screening and optimizing method based on combinatorial chemistry and scanning electrochemical microscopy (SECM). A homogeneous TiO2 catalyst layer is coated on a FTO substrate, which is then covered by a dark mask to expose the photocatalyst array. On each photocatalyst spot, different successive ionic layer adsorption and reaction (SILAR) processes are performed by a programmed solution dispenser to load the binary PbxCd1-xS QDs sensitizers. An optical fiber is employed as the scanning tip of SECM, and the photocatalytic current is recorded during the imaging experiment, through which the optimized technical parameters are figured out. To verify the validity of the combinatorial SECM imaging results, the controlled trials are performed with the corresponding photovoltaic demo devices. The harmonious accordance proved that the methodology based on combinatorial chemistry and SECM is valuable for the interfacial construction, high-throughput screening, and optimization of QDSSCs. Furthermore, the PbxCd1-xS/CdS QDs cosensitized solar cell optimized by SECM achieves a short circuit current density of 24.47 mA/cm(2), an open circuit potential of 421 mV, a fill factor of 0.52, and a photovoltaic conversion efficiency of 5.33%. PMID- 27355524 TI - Bone Failure in Critical Illness. AB - OBJECTIVES: The origin of systemic inflammatory response syndrome and multiple organ dysfunction syndrome is poorly understood but remains a fundamental concern in the ICU. This paper provides a critical appraisal on whether bone failure may represent an unrecognized component of systemic inflammatory response syndrome/multiple organ dysfunction syndrome. DATA SOURCES, DATA SELECTION, AND DATA EXTRACTION: Search of the PubMed database and manual review of selected articles investigating bone pathophysiology in critical illness. DATA SYNTHESIS: Bone hyperresorption is highly prevalent among critically ill patients. Bone breakdown releases numerous systemically active cytokines and bone-sequestered toxins, with the capacity to fuel inflammatory hypercytokinaemia and metabolic toxaemia. Anti-resorptive medication inhibits bone break down and preadmission anti-resorptive use is associated with superior survival among critically ill patients. CONCLUSIONS: We propose that hyperresorptive bone failure is an unrecognised component of systemic inflammatory response syndrome/multiple organ dysfunction syndrome that is causal to critical illness progression. If this hypothesis is valid, bone preservative strategies could reduce the risk of osteoporosis/fractures among ICU survivors, as well as decreasing critical illness mortality. PMID- 27355525 TI - Impact of Weight Extremes on Clinical Outcomes in Pediatric Acute Respiratory Distress Syndrome. AB - OBJECTIVES: To determine whether weight extremes impact clinical outcomes in pediatric acute respiratory distress syndrome. DESIGN: Post hoc analysis of a cohort created by combining five multicenter pediatric acute respiratory distress syndrome studies. SETTING: Forty-three academic PICUs worldwide. PATIENTS: A total of 711 subjects prospectively diagnosed with pediatric acute respiratory distress syndrome. INTERVENTION: Subjects more than 2 years were included and categorized by Center for Disease Control and Prevention body mass index z score criteria: underweight (< -1.89), normal weight (-1.89 to +1.04), overweight (+1.05 to +1.64), and obese (>= +1.65). Subjects were stratified by direct versus indirect lung injury leading to pediatric acute respiratory distress syndrome. The primary outcome was in-hospital mortality. In survivors, secondary analyses included duration of mechanical ventilation and ICU length of stay. MEASUREMENTS AND MAIN RESULTS: A total of 331 patients met inclusion criteria; 12% were underweight, 50% normal weight, 11% overweight, and 27% obese. Overall mortality was 20%. By multivariate analysis, body mass index category was independently associated with mortality (p = 0.004). When stratified by lung injury type, there was no mortality difference between body mass index groups with direct lung injury; however, in the indirect lung injury group, the odds of mortality in the obese were significantly lower than normal weight subjects (odds ratio, 0.11; 95% CI, 0.02-0.84). Survivors with direct lung injury had no difference in the duration of mechanical ventilation or ICU length of stay; however, those with indirect lung injury, the overweight required longer duration of mechanical ventilation than other groups (p < 0.001). CONCLUSIONS: These data support the obesity paradox in pediatric acute respiratory distress syndrome. Obese children with indirect lung injury pediatric acute respiratory distress syndrome have a lower risk of mortality. Importantly, among survivors, the overweight with indirect lung injury requires longer duration of mechanical ventilation. Our data require prospective validation to further elucidate the pathobiology of this phenomenon. PMID- 27355526 TI - Randomized Trial of Video Laryngoscopy for Endotracheal Intubation of Critically Ill Adults. AB - OBJECTIVE: To evaluate the effect of video laryngoscopy on the rate of endotracheal intubation on first laryngoscopy attempt among critically ill adults. DESIGN: A randomized, parallel-group, pragmatic trial of video compared with direct laryngoscopy for 150 adults undergoing endotracheal intubation by Pulmonary and Critical Care Medicine fellows. SETTING: Medical ICU in a tertiary, academic medical center. PATIENTS: Critically ill patients 18 years old or older. INTERVENTIONS: Patients were randomized 1:1 to video or direct laryngoscopy for the first attempt at endotracheal intubation. MEASUREMENTS AND MAIN RESULTS: Patients assigned to video (n = 74) and direct (n = 76) laryngoscopy were similar at baseline. Despite better glottic visualization with video laryngoscopy, there was no difference in the primary outcome of intubation on the first laryngoscopy attempt (video 68.9% vs direct 65.8%; p = 0.68) in unadjusted analyses or after adjustment for the operator's previous experience with the assigned device (odds ratio for video laryngoscopy on intubation on first attempt 2.02; 95% CI, 0.82 5.02, p = 0.12). Secondary outcomes of time to intubation, lowest arterial oxygen saturation, complications, and in-hospital mortality were not different between video and direct laryngoscopy. CONCLUSIONS: In critically ill adults undergoing endotracheal intubation, video laryngoscopy improves glottic visualization but does not appear to increase procedural success or decrease complications. PMID- 27355527 TI - Urinary Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor Binding Protein 7 for Risk Stratification of Acute Kidney Injury in Patients With Sepsis. AB - OBJECTIVES: To examine the performance of the urinary biomarker panel tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in patients with sepsis at ICU admission. To investigate the effect of nonrenal organ dysfunction on tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in this population. METHOD: In this ancillary analysis, we included patients with sepsis who were enrolled in either of two trials including 39 ICUs across Europe and North America. The primary endpoint was moderate-severe acute kidney injury (equivalent to Kidney Disease Improving Global Outcome stage 2-3) within 12 hours of enrollment. We assessed biomarker performance by calculating the area under the receiver operating characteristic curve, sensitivity, specificity, and negative and positive predictive values at three cutoffs: 0.3, 1.0, and 2.0 (ng/mL)/1,000. We also calculated nonrenal Sequential Organ Failure Assessment scores for each patient on enrollment and compared tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 results in patients with and without acute kidney injury and across nonrenal Sequential Organ Failure Assessment scores. Finally, we constructed a clinical model for acute kidney injury in this population and compared the performance of the model with and without tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7. RESULTS: We included 232 patients in the analysis and 40 (17%) developed acute kidney injury. We observed significantly higher urine tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in patients with acute kidney injury than without acute kidney injury in both patients with low and high nonrenal Sequential Organ Failure Assessment scores (p < 0.001). The area under the receiver operating characteristic curve (95% CI) of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 was 0.84 (0.73-0.92) and 0.85 (0.76-0.94), in low and high nonrenal Sequential Organ Failure Assessment score subgroups. Performance of the tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 test was not modified by nonrenal Sequential Organ Failure Assessment (p = 0.70). In multivariate analysis, the addition of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 significantly improved the performance of a clinical model for predicting acute kidney injury (p = 0.015). CONCLUSION: Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 accurately predicts acute kidney injury in septic patients with or without other organ failures. PMID- 27355528 TI - Dual tumor-suppressors miR-139-5p and miR-139-3p targeting matrix metalloprotease 11 in bladder cancer. AB - Our recent study of the microRNA (miRNA) expression signature of bladder cancer (BC) by deep-sequencing revealed that two miRNA, microRNA-139-5p/microRNA-139-3p were significantly downregulated in BC tissues. The aim of this study was to investigate the functional roles of these miRNA and their modulation of cancer networks in BC cells. Functional assays of BC cells were performed using transfection of mature miRNA or small interfering RNA (siRNA). Genome-wide gene expression analysis, in silico analysis and dual-luciferase reporter assays were applied to identify miRNA targets. The associations between the expression of miRNA and its targets and overall survival were estimated by the Kaplan-Meier method. Gain-of-function studies showed that miR-139-5p and miR-139-3p significantly inhibited cell migration and invasion by BC cells. The matrix metalloprotease 11 gene (MMP11) was identified as a direct target of miR-139-5p and miR-139-3p. Kaplan-Meier survival curves showed that higher expression of MMP11 predicted shorter survival of BC patients (P = 0.029). Downregulated miR 139-5p or miR-139-3p enhanced BC cell migration and invasion in BC cells. MMP11 was directly regulated by these miRNA and might be a good prognostic marker for survival of BC patients. PMID- 27355529 TI - Saving the World's Women from Cervical Cancer. PMID- 27355530 TI - Time for a Model List of Essential Diagnostics. PMID- 27355531 TI - Passing the Baton--Harnessing the Full Value of Older Scientists. PMID- 27355532 TI - Seven-Year Efficacy of RTS,S/AS01 Malaria Vaccine among Young African Children. AB - BACKGROUND: The candidate malaria vaccine RTS,S/AS01 is being evaluated in order to inform a decision regarding its inclusion in routine vaccination schedules. METHODS: We conducted 7 years of follow-up in children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of either the RTS,S/AS01 vaccine or a rabies (control) vaccine. The end point was clinical malaria (temperature of >=37.5 degrees C and infection with Plasmodium falciparum of >2500 parasites per cubic millimeter). In an analysis that was not prespecified, the malaria exposure of each child was estimated with the use of information on the prevalence of malaria among residents within a 1-km radius of the child's home. Vaccine efficacy was defined as 1 minus the hazard ratio or the incidence-rate ratio, multiplied by 100, in the RTS,S/AS01 group versus the control group. RESULTS: Over 7 years of follow-up, we identified 1002 episodes of clinical malaria among 223 children randomly assigned to the RTS,S/AS01 group and 992 episodes among 224 children randomly assigned to the control group. The vaccine efficacy, as assessed by negative binomial regression, was 4.4% (95% confidence interval [CI], -17.0 to 21.9; P=0.66) in the intention-to-treat analysis and 7.0% (95% CI, -14.5 to 24.6; P=0.52) in the per-protocol analysis. Vaccine efficacy waned over time (P=0.006 for the interaction between vaccination and time), including negative efficacy during the fifth year among children with higher-than-average exposure to malaria parasites (intention-to-treat analysis: 43.5%; 95% CI, -100.3 to -2.8 [P=0.03]; per-protocol analysis: -56.8%; 95% CI, 118.7 to -12.3 [P=0.008]). CONCLUSIONS: A three-dose vaccination with RTS,S/AS01 was initially protective against clinical malaria, but this result was offset by rebound in later years in areas with higher-than-average exposure to malaria parasites. (Funded by the PATH Malaria Vaccine Initiative and others; ClinicalTrials.gov number, NCT00872963.). PMID- 27355533 TI - Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis. AB - BACKGROUND: Advanced systemic mastocytosis comprises rare hematologic neoplasms that are associated with a poor prognosis and lack effective treatment options. The multikinase inhibitor midostaurin inhibits KIT D816V, a primary driver of disease pathogenesis. METHODS: We conducted an open-label study of oral midostaurin at a dose of 100 mg twice daily in 116 patients, of whom 89 with mastocytosis-related organ damage were eligible for inclusion in the primary efficacy population; 16 had aggressive systemic mastocytosis, 57 had systemic mastocytosis with an associated hematologic neoplasm, and 16 had mast-cell leukemia. The primary outcome was the best overall response. RESULTS: The overall response rate was 60% (95% confidence interval [CI], 49 to 70); 45% of the patients had a major response, which was defined as complete resolution of at least one type of mastocytosis-related organ damage. Response rates were similar regardless of the subtype of advanced systemic mastocytosis, KIT mutation status, or exposure to previous therapy. The median best percentage changes in bone marrow mast-cell burden and serum tryptase level were -59% and -58%, respectively. The median overall survival was 28.7 months, and the median progression-free survival was 14.1 months. Among the 16 patients with mast-cell leukemia, the median overall survival was 9.4 months (95% CI, 7.5 to not estimated). Dose reduction owing to toxic effects occurred in 56% of the patients; re-escalation to the starting dose was feasible in 32% of those patients. The most frequent adverse events were low-grade nausea, vomiting, and diarrhea. New or worsening grade 3 or 4 neutropenia, anemia, and thrombocytopenia occurred in 24%, 41%, and 29% of the patients, respectively, mostly in those with preexisting cytopenias. CONCLUSIONS: In this open-label study, midostaurin showed efficacy in patients with advanced systemic mastocytosis, including the highly fatal variant mast-cell leukemia. (Funded by Novartis Pharmaceuticals and others; ClinicalTrials.gov number, NCT00782067.). PMID- 27355535 TI - Ankylosing Spondylitis and Axial Spondyloarthritis. PMID- 27355534 TI - Cortical-Bone Fragility--Insights from sFRP4 Deficiency in Pyle's Disease. AB - BACKGROUND: Cortical-bone fragility is a common feature in osteoporosis that is linked to nonvertebral fractures. Regulation of cortical-bone homeostasis has proved elusive. The study of genetic disorders of the skeleton can yield insights that fuel experimental therapeutic approaches to the treatment of rare disorders and common skeletal ailments. METHODS: We evaluated four patients with Pyle's disease, a genetic disorder that is characterized by cortical-bone thinning, limb deformity, and fractures; two patients were examined by means of exome sequencing, and two were examined by means of Sanger sequencing. After a candidate gene was identified, we generated a knockout mouse model that manifested the phenotype and studied the mechanisms responsible for altered bone architecture. RESULTS: In all affected patients, we found biallelic truncating mutations in SFRP4, the gene encoding secreted frizzled-related protein 4, a soluble Wnt inhibitor. Mice deficient in Sfrp4, like persons with Pyle's disease, have increased amounts of trabecular bone and unusually thin cortical bone, as a result of differential regulation of Wnt and bone morphogenetic protein (BMP) signaling in these two bone compartments. Treatment of Sfrp4-deficient mice with a soluble Bmp2 receptor (RAP-661) or with antibodies to sclerostin corrected the cortical-bone defect. CONCLUSIONS: Our study showed that Pyle's disease was caused by a deficiency of sFRP4, that cortical-bone and trabecular-bone homeostasis were governed by different mechanisms, and that sFRP4-mediated cross regulation between Wnt and BMP signaling was critical for achieving proper cortical-bone thickness and stability. (Funded by the Swiss National Foundation and the National Institutes of Health.). PMID- 27355537 TI - IMAGES IN CLINICAL MEDICINE. Oral HPV-Associated Papillomatosis in AIDS. PMID- 27355536 TI - Calcium Pyrophosphate Deposition Disease. PMID- 27355538 TI - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 20-2016. A 50-Year-Old Man with Cloudy Vision, Hearing Loss, and Unsteadiness. PMID- 27355539 TI - NEJM Resident 360. PMID- 27355540 TI - Implementation of RTS,S/AS01 Malaria Vaccine--The Need for Further Evidence. PMID- 27355541 TI - Belatacept and Long-Term Outcomes in Kidney Transplantation. PMID- 27355542 TI - Belatacept and Long-Term Outcomes in Kidney Transplantation. PMID- 27355543 TI - Belatacept and Long-Term Outcomes in Kidney Transplantation. PMID- 27355544 TI - Belatacept and Long-Term Outcomes in Kidney Transplantation. PMID- 27355545 TI - Belatacept and Long-Term Outcomes in Kidney Transplantation. PMID- 27355546 TI - Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies. PMID- 27355547 TI - Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies. PMID- 27355548 TI - Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies. PMID- 27355549 TI - Weekly vs. Every-3-Week Paclitaxel for Ovarian Cancer. PMID- 27355550 TI - Weekly vs. Every-3-Week Paclitaxel for Ovarian Cancer. PMID- 27355551 TI - Weekly vs. Every-3-Week Paclitaxel for Ovarian Cancer. PMID- 27355552 TI - A Leadless Intracardiac Transcatheter Pacing System. PMID- 27355553 TI - A Leadless Intracardiac Transcatheter Pacing System. PMID- 27355554 TI - Tragedy, Trade-offs, and the Demise of Morcellation. PMID- 27355556 TI - IMAGES IN CLINICAL MEDICINE. Hypopyon and Klebsiella Sepsis. PMID- 27355555 TI - Midostaurin in Advanced Systemic Mastocytosis. PMID- 27355557 TI - Metabolism of 4-Hydroxy-7-oxo-5-heptenoic Acid (HOHA) Lactone by Retinal Pigmented Epithelial Cells. AB - 4-Hydroxy-7-oxo-5-heptenic acid (HOHA)-lactone is a biologically active oxidative truncation product released (t1/2 = 30 min at 37 degrees C) by nonenzymatic transesterification/deacylation from docosahexaenoate lipids. We now report that HOHA-lactone readily diffuses into retinal pigmented epithelial (RPE) cells where it is metabolized. A reduced glutathione (GSH) Michael adduct of HOHA-lactone is the most prominent metabolite detected by LC-MS in both the extracellular medium and cell lysates. This molecule appeared inside of ARPE-19 cells within seconds after exposure to HOHA-lactone. The intracellular level reached a maximum concentration at 30 min and then decreased with concomitant increases in its level in the extracellular medium, thus revealing a unidirectional export of the reduced GSH-HOHA-lactone adduct from the cytosol to extracellular medium. This metabolism is likely to modulate the involvement of HOHA-lactone in the pathogenesis of human diseases. HOHA-lactone is biologically active, e.g., low concentrations (0.1-1 MUM) induce secretion of vascular endothelial growth factor (VEGF) from ARPE-19 cells. HOHA-lactone is also a precursor of 2-(omega carboxyethyl)pyrrole (CEP) derivatives of primary amino groups in proteins and ethanolamine phospholipids that have significant pathological and physiological relevance to age-related macular degeneration (AMD), cancer, and wound healing. Both HOHA-lactone and the derived CEP can contribute to the angiogenesis that defines the neovascular "wet" form of AMD and that promotes the growth of tumors. While GSH depletion can increase the lethality of radiotherapy, because it will impair the metabolism of HOHA-lactone, the present study suggests that GSH depletion will also increase levels of HOHA-lactone and CEP that may promote recurrence of tumor growth. PMID- 27355558 TI - Effects of electromagnetic pulse exposure on gelatinase of blood-brain barrier in vitro. AB - The biological effects of electromagnetic pulse (EMP) on the brain have been focused on for years. It was reported that gelatinase played an important role in maintaining brain function through regulating permeability in the blood-brain barrier (BBB). To investigate the effects of EMP on gelatinase of BBB, an in vitro BBB model was established using primary cultured rat brain microvascular endothelial cells (BMVEC), astrocytes and half-contact culture of these cells in a transwell chamber. Cultured supernatant and cells were collected at different time points after exposure to EMP (peak intensity 400 kV/m, rise time 10 ns, pulse width 350 ns, 0.5 pps and 200 pulses). Protein levels of cellular gelatinase MMP-2 and MMP-9, and endogenous inhibitor TIMP-1 and TIMP-2 were detected by Western blot. The activity of gelatinase in culture supernatant was detected by gelatin zymography. It was found that compared with the sham-exposed group, the protein level of MMP-2 was significantly increased at 6 h (p < 0.05), and the protein level of its endogenous inhibitor TIMP-2 did not change after EMP exposure. In addition, the protein levels of MMP-9 and its endogenous inhibitor TIMP-1 did not change after EMP exposure. Gelatin zymography results showed that the activity of MMP-2 in the inner pool and the outer pool of the transwell chamber was significantly increased at 6 h after EMP exposure compared with that of the sham group. These results suggested that EMP exposure could affect the expression and activity of MMP-2 in the BBB model. PMID- 27355559 TI - Synthesis of 1,2,4-Triazolo[4,3-a]pyridines and Related Heterocycles by Sequential Condensation and Iodine-Mediated Oxidative Cyclization. AB - A facile and efficient approach to access 1,2,4-triazolo[4,3-a]pyridines and related heterocycles has been accomplished through condensation of readily available aryl hydrazines with corresponding aldehydes followed by iodine mediated oxidative cyclization. This transition-metal-free synthetic process is broadly applicable to a variety of aromatic, aliphatic, and alpha,beta unsaturated aldehydes, and can be conveniently conducted on the gram scale. PMID- 27355560 TI - Increase of Serum CXCL16 Level Correlates Well to Microembolic Signals in Acute Stroke Patients with Carotid Artery Stenosis. AB - BACKGROUND: The majority of strokes are combined with the instability of atherosclerotic plaques. Microembolic signals (MES) have been considered as evidence of plaque destabilization. We found that increased CXCL16 correlated to atherosclerotic ischemic stroke. Thus, we explored whether CXCL16 correlates to MES. METHODS: The study recruited 104 controls and 118 patients with acute ischemic stroke that has an ipsilateral carotid artery stenosis of >50%. The ipsilateral middle cerebral artery of patients was insonated for 60min using Doppler device within 72h of their clinical presentation. RESULTS: We found that CXCL16 was significantly increased in the stroke patients. Furthermore, there was a significant difference in CXCL16 between the MES-positive and MES-negative patients. Using CXCL16 to distinguish the controls and stroke patients, the area under the ROC curve (AUC) was 0.722; the cut-off value was 2.015ng/ml. The sensitivity and specificity were 70.5% and 67.9%, respectively. Furthermore, if we used CXCL16 to distinguish the MES-positive and MES-negative patients, the AUC was 0.736; the cut-off value was 2.115ng/ml. The sensitivity and specificity were 88.5% and 56.5%, respectively. CONCLUSIONS: Higher levels CXCL16 may be a biomarker for predicting stroke incidence and might contribute to plaque destabilization. PMID- 27355561 TI - Realizing Highly Efficient Inverted Photovoltaic Cells by Combination of Nonconjugated Small-Molecule Zwitterions with Polyethylene Glycol. AB - Organic ionic materials have been reported to be efficient cathode interlayer (CIL) materials in polymer solar cells (PSCs); however, most of them are employed in conventional PSCs. For an inverted structural device which has better stability, the efficiency is still far from expectation and the report is also limited. In this study, by using nonconjugated zwitterions as the CIL and inverted structure, the power conversion efficiency (PCE) is ~6%, though the PCE can reach 9.14% in the conventional device. By introducing polyethylene glycol (PEG) into the zwitterions, the PCE of the inverted PSCs was improved ~33% and reached ~8% mainly because of the enhancement of the open-circuit voltage (Voc) and fill factor (FF). Further research on the device parameters, work functions, morphology of indium tin oxide (ITO) with various CILs, and recombination resistance of the devices indicated that PEG + zwitterion induced not only a lower work function of ITO but also a more uniform morphology of CILs with less contact of the photoactive layer with ITO, which induced suppressed charge recombination and a higher Voc and FF. Enhanced ability in interface modification of PEG + zwitterion CILs displayed a simple and feasible approach to elevate the performance of inverted PSCs with ionic CILs. PMID- 27355562 TI - Improved Discrimination for Brassica Vegetables Treated with Agricultural Fertilizers Using a Combined Chemometric Approach. AB - Multielement and stable isotope (delta(13)C, delta(15)N, delta(2)H, delta(18)O, (207)Pb/(206)Pb, and (208)Pb/(206)Pb) analyses were combined to provide a new chemometric approach to improve the discrimination between organic and conventional Brassica vegetable production. Different combinations of organic and conventional fertilizer treatments were used to demonstrate this authentication approach using Brassica chinensis planted in experimental test pots. Stable isotope analyses (delta(15)N and delta(13)C) of B. chinensis using elemental analyzer-isotope ratio mass spectrometry easily distinguished organic and chemical fertilizer treatments. However, for low-level application fertilizer treatments, this dual isotope approach became indistinguishable over time. Using a chemometric approach (combined isotope and elemental approach), organic and chemical fertilizer mixes and low-level applications of synthetic and organic fertilizers were detectable in B. chinensis and their associated soils, improving the detection limit beyond the capacity of individual isotopes or elemental characterization. LDA shows strong promise as an improved method to discriminate genuine organic Brassica vegetables from produce treated with chemical fertilizers and could be used as a robust test for organic produce authentication. PMID- 27355563 TI - The Mammalian Hairless Protein as a DNA Binding Phosphoprotein. AB - The mammalian hairless (Hr) protein plays critical roles in skin and brain tissues, but how it interacts with DNA and partner protein is only now being defined. Our initial tests of four consensus response elements, revealed that rat Hr can specifically bind to a consensus p53 response element (p53RE), 5' AGACATGCCTAGACATGCCT-3', but not to response elements for NF-kappaB, TCF4 or Sp1. We then employed ChIP assays which verified that human HR binds to a p53RE of the GADD45A gene in both HEK293 (embryonic kidney) and U87 (glioblastoma) cells. Further, HR was shown to interact directly with the p53 protein in a co immunoprecipitation assay. Cotransfections with p53RE reporter gene constructs revealed that rat Hr can boost p53-mediated transactivation of a reporter gene linked to the GADD45A p53RE, but blunts p53-mediated transactivation when the reporter gene is linked to a p21 promoter fragment containing a p53RE, with implications for the regulation of these two cell cycle control genes. Finally, our investigations of HR phosphorylation revealed that rat Hr is a substrate for PKC, but not PKA, and that human HR is phosphorylated in intact U87 cells at Ser 416, located in a highly conserved region which partially fulfills the criteria of a PKC site. We propose that mammalian Hr is a phosphoprotein which can exert cross-talk with the p53 pathway with important implications for the regulation of cell proliferation and differentiation in tissues such as skin and brain where Hr is highly expressed. J. Cell. Biochem. 118: 341-350, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27355565 TI - Hormone-sensitive lipase deficiency disturbs lipid composition of plasma membrane microdomains from mouse testis. PMID- 27355564 TI - Low Plasma Level of Leucine-Rich Repeat-Containing 17 (LRRc17) Is an Independent and Additive Risk Factor for Osteoporotic Fractures in Postmenopausal Women. AB - A novel role of leucine-rich repeat-containing 17 (LRRc17), an LRR protein secreted by osteoblasts, as a negative regulator of receptor activator of NF kappaB ligand-induced osteoclast differentiation was found. However, the clinical association between LRRc17 and osteoporotic fracture (OF) has not yet been investigated. We hypothesized that low circulating plasma level of LRRc17 might serve as an independent and additive risk factor for OF, including vertebral fractures (VF) and non-vertebral fractures (non-VF). In this case-control study, 102 OF cases and 102 age- and body mass index-matched controls (mean age, 63.2 years) were analyzed among 532 postmenopausal women. VF (n = 49) and non-VF (n = 60) participants were identified using lateral thoracolumbar radiographs and an interviewer-assisted questionnaire, respectively. Median LRRc17 levels were significantly lower in participants with any OF (117.5 versus 197.3 pg/mL, p < 0.001), VF (93.2 versus 172.4 pg/mL, p = 0.002), and non-VF (124.5 versus 206.9 pg/mL, p = 0.008) compared with the respective controls without fractures. The prevalence of OF increased from the highest LRRc17 tertile (>=228.5 pg/mL, 33.8%) to the lowest (<95.6 pg/mL, 63.2%). Each log unit decrease of LRRc17 was associated with greater risk of OF (odds ratio [OR] = 1.46; 95% confidence interval [CI] 1.10-1.96; p = 0.009) and VF (OR = 2.42; 95% CI 1.39-4.23; p = 0.002). Plasma LRRc17 significantly improved discrimination of OF, particularly VF, when added to models including clinical risk factors and bone mineral density according to the area under receiver operating characteristics curves (AUC 0.71 to 0.81, p = 0.036), category-free net reclassification improvement (0.79; 95% CI 0.37-1.21; p < 0.001), and integrated discrimination improvement (0.13; 95% CI 0.06-0.20; p < 0.001). Low plasma LRRc17 was an independent risk factor for OF, which improved risk stratification, particularly in the spines of postmenopausal women. (c) 2016 American Society for Bone and Mineral Research. PMID- 27355566 TI - Malondialdehyde epitopes as mediators of sterile inflammation. AB - Enhanced lipid peroxidation occurs during oxidative stress and results in the generation of lipid peroxidation end products such as malondialdehyde (MDA), which can attach to autologous biomolecules, thereby generating neo-self epitopes capable of inducing potentially undesired biological responses. Therefore, the immune system has developed mechanisms to protect from MDA epitopes by binding and neutralizing them through both cellular and soluble effectors. Here, we briefly discuss innate immune responses targeting MDA epitopes and their pro inflammatory properties, followed by a review of physiological carriers of MDA epitopes that are relevant in homeostasis and disease. Then we discuss in detail the evidence for cellular responses towards MDA epitopes mainly in lung, liver and the circulation as well as signal transduction mechanisms and receptors implicated in the response to MDA epitopes. Last, we hypothesize on the role of MDA epitopes as mediators of inflammation in diseases and speculate on their contribution to disease pathogenesis. This article is part of a Special Issue entitled: Lipid modification and lipid peroxidation products in innate immunity and inflammation edited by Christoph J. Binder. PMID- 27355567 TI - Pure Cubic-Phase Hybrid Iodobismuthates AgBi2 I7 for Thin-Film Photovoltaics. AB - Bismuth-based hybrid perovskites are candidates for lead-free and air-stable photovoltaics, but poor surface morphologies and a high band-gap energy have previously limited these hybrid perovskites. A new materials processing strategy to produce enhanced bismuth-based thin-film photovoltaic absorbers by incorporation of monovalent silver cations into iodobismuthates is presented. Solution-processed AgBi2 I7 thin films are prepared by spin-coating silver and bismuth precursors dissolved in n-butylamine and annealing under an N2 atmosphere. X-ray diffraction analysis reveals the pure cubic structure (Fd3m) with lattice parameters of a=b=c=12.223 A. The resultant AgBi2 I7 thin films exhibit dense and pinhole-free surface morphologies with grains ranging in size from 200-800 nm and a low band gap of 1.87 eV suitable for photovoltaic applications. Initial studies produce solar power conversion efficiencies of 1.22 % and excellent stability over at least 10 days under ambient conditions. PMID- 27355568 TI - A Frustrated Phosphane-Borane Lewis Pair and Hydrogen: A Kinetics Study. AB - The energy profile of a frustrated Lewis pair (FLP) dihydrogen splitting system was determined by a combined experimental kinetic and DFT study. A trimethylene bridged phosphane-borane FLP was converted into its endothermic H2 -cleavage product by sequential H(+) /H(-) addition. The system could be handled at low temperature, and the kinetics of the H2 elimination were determined to give a rate constant of kHH,exp (299 K)=(2.87+/-0.1)*10(-4) s(-1) in solution. The primary kinetic isotope effects were determined; for example, (kHH /kDD )exp =3.19. The system was accurately analyzed by DFT calculations. PMID- 27355571 TI - p21 governs p53's repressive side. PMID- 27355570 TI - Vaccine protection against Zika virus from Brazil. AB - Zika virus (ZIKV) is a flavivirus that is responsible for the current epidemic in Brazil and the Americas. ZIKV has been causally associated with fetal microcephaly, intrauterine growth restriction, and other birth defects in both humans and mice. The rapid development of a safe and effective ZIKV vaccine is a global health priority, but very little is currently known about ZIKV immunology and mechanisms of immune protection. Here we show that a single immunization with a plasmid DNA vaccine or a purified inactivated virus vaccine provides complete protection in susceptible mice against challenge with a strain of ZIKV involved in the outbreak in northeast Brazil. This ZIKV strain has recently been shown to cross the placenta and to induce fetal microcephaly and other congenital malformations in mice. We produced DNA vaccines expressing ZIKV pre-membrane and envelope (prM-Env), as well as a series of deletion mutants. The prM-Env DNA vaccine, but not the deletion mutants, afforded complete protection against ZIKV, as measured by absence of detectable viraemia following challenge, and protective efficacy correlated with Env-specific antibody titers. Adoptive transfer of purified IgG from vaccinated mice conferred passive protection, and depletion of CD4 and CD8 T lymphocytes in vaccinated mice did not abrogate this protection. These data demonstrate that protection against ZIKV challenge can be achieved by single-shot subunit and inactivated virus vaccines in mice and that Env-specific antibody titers represent key immunologic correlates of protection. Our findings suggest that the development of a ZIKV vaccine for humans is likely to be achievable. PMID- 27355572 TI - Use of an Abdominal Binder to Minimize Postprocedural Complications After Cutaneous Surgery on the Trunk. PMID- 27355573 TI - Repair of an Inferior Helical Rim Defect. PMID- 27355574 TI - Emerging Points of the Supraorbital and Supratrochlear Nerves in the Supraorbital Margin With Reference to the Lacrimal Caruncle: Implications for Regional Nerve Block in Upper Eyelid and Dermatologic Surgery. AB - BACKGROUND: Blocking the supraorbital nerve (SON) and supratrochlear nerve (STN) by injecting anesthetic distal to the surgical site has the advantage in upper eyelid surgery that avoids obscuring the surgical landmarks and compromising the levator function. OBJECTIVE: To identify the emerging points of the SON and STN in the supraorbital margin with reference to the lacrimal caruncle. METHODS: Forty-nine orbits from 27 embalmed Korean cadavers were dissected. The lacrimal caruncle and facial midline were used as landmarks. The emerging points of the SON and STN in the supraorbital margin were determined. RESULTS: The emerging points of the SON and STN were, respectively, located at 3.0 mm lateral and 3.3 mm medial to the vertical line through the apex of the lacrimal caruncle along the supraorbital margin. The horizontal distances from the facial midline to the emerging points of the SON and STN were 22.8 and 15.2 mm, respectively. CONCLUSION: The optimum sites for achieving SON and STN block are, respectively, located approximately 3 mm lateral and 3 mm medial to the vertical line through the apex of lacrimal caruncle along the supraorbital margin. This knowledge will help the surgeon achieve an easy and accurate approach for regional nerve block. PMID- 27355575 TI - Neuropsychiatry of fragile X-premutation carriers with and without fragile X associated tremor-ataxia syndrome: implications for neuropsychology. AB - OBJECTIVES: Clinical neuropsychologists benefit from clinical currency in recently ascertained neuropsychiatric illness, such as fragile X premutation (FXPM) disorders. The author reviewed the clinical literature through 2016 for neuropsychiatric phenotypes in FXPM disorders, including patients with fragile X associated tremor/ataxia syndrome (FXTAS). METHODS: A PubMed search using the search terms 'Fragile X,' 'Premutation,' 'Carriers,' 'Psychiatric,' 'Dementia,' 'Mood,' and 'Anxiety' for citations in the clinical literature through 2016 was reviewed for studies specifically examining the neuropsychiatric phenotype in FXPM patients. The relevant articles were classified according to specific neuropsychiatric syndromes, including child onset, adult onset with and without FXTAS, as well as common systemic comorbidities in FXPM patients. RESULTS: Eighty six articles were reviewed for the neuropsychiatric and other phenotypes in FXPM patients. The neuropsychiatric phenotype in FXPM patients is distinct from that of full mutation (Fragile X Syndrome) patients. FXTAS is associated with a specific cortical-subcortical major or mild neurocognitive disorder (NCD). CONCLUSIONS: FXPM patients are at risk for neuropsychiatric illness. In addition, FXPM patients are at risk for other systemic conditions that should raise suspicion for FXPM-associated illnesses. Clinicians should consider a diagnosis of FXPM-associated neuropsychiatric illness when patients with specific clinical scenarios are encountered; especially in patient pedigrees consistent with a typical (often multigenerational) presentation of fragile X-associated conditions, confirmatory genetic testing should be considered. Clinical management should take into account the psychological challenges of a multigenerational genetic neuropsychiatric illness with a variable CNS and systemic clinical phenotype. PMID- 27355576 TI - Barriers to Effective Postmenopausal Osteoporosis Treatment: A Qualitative Study of Patients' and Practitioners' Views. AB - BACKGROUND: Only a minority of patients at high risk for osteoporotic fracture receive treatment. OBJECTIVE: Study patients' and physicians' views regarding postmenopausal osteoporosis (PMO) to identify impediments to good care. METHODS: A qualitative study involving 18 physicians and 37 women (age 57-87) with PMO. RESULTS: All women interviewed considered PMO to be somewhat normal wear-and-tear associated with old age. The women identified a large number of "causes" for osteoporosis but finally viewed it as chance. They all described its progression as slow. Three representations of PMO severity were identified: some women tended to interpreted it as benign (21), others tended to dramatize it (11), and the rest were uncertain (5). These representations did not appear linked to age or fracture. Even the women who associated fracture and PMO were uncertain of the link between them. Fractures were considered to be random events, independent of osteoporosis. Women received general life-style recommendations from their physicians positively, but did not connect them specifically to osteoporosis. Indeed, these recommendations, along with the fear of side effects, the absence of tangible results of treatments, the view of PMO as a natural process, and the representations of PMO severity are factors that may deter treatments and impact compliance. As for the physicians, they identified eight risk factors, recognizing menopause as central to PMO and recognized the link between risk of fracture and PMO. However, some considered the impact of fractures to be limited in time, and viewed PMO as a "benign" disease. Seeing the progression of PMO as slow and inevitable reduced their urgency to diagnose and treat it as compared to other diseases. Some physicians acknowledged limited mastery of the existing therapeutic arsenal and unsuccessful handling of patient compliance. CONCLUSION: Women's and physicians' perspectives on PMO converged to trivialize postmenopausal osteoporosis and thus disqualify it as a legitimate disease. A better understanding of women's and physicians' views, practices, and concerns related to PMO can improve osteoporosis management. PMID- 27355578 TI - An Improved Wavelet Packet-Chaos Model for Life Prediction of Space Relays Based on Volterra Series. AB - In this paper, an improved algorithm of wavelet packet-chaos model for life prediction of space relays based on volterra series is proposed. In the proposed method, the high and low frequency time sequence components of performance parameters are obtained by employing the improved wavelet packet transform to decompose the performance parameters of the relay into multiple scales. Then the optimization algorithm of parameters in volterra series is improved, and is used to construct a chaotic forecasting model for the high and low frequency time sequence components gained by the wavelet packet transform. At last, the chaotic forecasting results of the high and low frequency components are combined by taking the wavelet packet reconstruction approach, so as to predict the lifetime of the studied space relay. The algorithm can predict the life curve of the relay accurately and reflect the characteristics of the relay performance with sufficient accuracy. The proposed method is validated via a case study of a space relay. PMID- 27355577 TI - Alternating Current Stimulation for Vision Restoration after Optic Nerve Damage: A Randomized Clinical Trial. AB - BACKGROUND: Vision loss after optic neuropathy is considered irreversible. Here, repetitive transorbital alternating current stimulation (rtACS) was applied in partially blind patients with the goal of activating their residual vision. METHODS: We conducted a multicenter, prospective, randomized, double-blind, sham controlled trial in an ambulatory setting with daily application of rtACS (n = 45) or sham-stimulation (n = 37) for 50 min for a duration of 10 week days. A volunteer sample of patients with optic nerve damage (mean age 59.1 yrs) was recruited. The primary outcome measure for efficacy was super-threshold visual fields with 48 hrs after the last treatment day and at 2-months follow-up. Secondary outcome measures were near-threshold visual fields, reaction time, visual acuity, and resting-state EEGs to assess changes in brain physiology. RESULTS: The rtACS-treated group had a mean improvement in visual field of 24.0% which was significantly greater than after sham-stimulation (2.5%). This improvement persisted for at least 2 months in terms of both within- and between group comparisons. Secondary analyses revealed improvements of near-threshold visual fields in the central 5 degrees and increased thresholds in static perimetry after rtACS and improved reaction times, but visual acuity did not change compared to shams. Visual field improvement induced by rtACS was associated with EEG power-spectra and coherence alterations in visual cortical networks which are interpreted as signs of neuromodulation. Current flow simulation indicates current in the frontal cortex, eye, and optic nerve and in the subcortical but not in the cortical regions. CONCLUSION: rtACS treatment is a safe and effective means to partially restore vision after optic nerve damage probably by modulating brain plasticity. This class 1 evidence suggests that visual fields can be improved in a clinically meaningful way. TRIAL REGISTRATION: ClinicalTrials.gov NCT01280877. PMID- 27355580 TI - Pituitary Antibodies in an Adolescent with Secondary Adrenal Insufficiency and Turner Syndrome. AB - BACKGROUND/AIMS: Autoimmune hypophysitis (AH) is a rare inflammatory disease of the pituitary gland causing varying degrees of hypopituitarism and/or sellar compression. Cranial MRI remains the best noninvasive tool to diagnose AH, although a diagnosis of certainty requires pituitary biopsy. The objective of this study was to assess the utility of detecting pituitary antibodies for the diagnosis of AH. METHODS: A 15-year-old female with Turner syndrome (TS), hypothyroidism, and ovarian failure presented acutely with hypocortisolism. Laboratory studies revealed secondary adrenal insufficiency. MRI showed a hypotrophic pituitary gland and loss of the posterior pituitary bright spot. To establish an autoimmune basis for the adrenal insufficiency, serum was analyzed by double indirect immunofluorescence for the presence of pituitary autoantibodies. RESULTS: The patient's serum contained autoantibodies that recognized 36% of the adrenocorticotropic hormone-secreting cells, suggesting that these adenohypophyseal cells were targeted by autoimmunity. The serum contained antibodies that identified the majority of the gonadotropin-secreting cells (FSH 77%, LH 65%). No recognition of GH-, prolactin-, and TSH-secreting cells was found. Preabsorption experiments showed that antigenic targets of autoantibodies were not anterior pituitary hormones themselves. CONCLUSION: Demonstration of circulating pituitary antibodies expands the diagnostic options for AH. In this adolescent with TS, positive and cell-specific pituitary antibodies suggested that AH was the cause of her secondary adrenal insufficiency. PMID- 27355581 TI - Protective Effect of Irisin on Atherosclerosis via Suppressing Oxidized Low Density Lipoprotein Induced Vascular Inflammation and Endothelial Dysfunction. AB - Irisin, a newly discovered myokine, is considered as a promising candidate for the treatment of metabolic disturbances and cardiovascular diseases. In the present study, we used two animal models, apolipoprotein E-deficient mice fed on a high-cholesterol diet and a mouse carotid partial ligation model to test the anti-atherosclerotic effect of irisin. Irisin treatment (0.5 MUg/g body weight/day) significantly reduced the severity of aortic atherosclerosis in apolipoprotein E-deficient mice fed on a high-cholesterol diet and suppressed carotid neointima formation in a carotid partial ligation model. It was associated with decreased inflammation and cell apoptosis in aortic tissues. In addition, in a cell culture model, irisin restored ox-LDL-induced human umbilical vein endothelial cell dysfunction by reducing the levels of inflammatory genes via inhibiting the reactive oxygen species (ROS)/ p38 MAPK/ NF-kappaB signaling pathway activation and inhibiting cell apoptosis via up-regulating Bcl-2 and down regulating Bax and caspase-3 expression. Our study demonstrated that irisin significantly reduced atherosclerosis in apolipoprotein E-deficient mice via suppressing ox-LDL-induced cell inflammation and apoptosis, which might have a direct therapeutic effect on atherosclerotic diseases. PMID- 27355582 TI - Evaluation of X Chromosome Inactivation with Respect to HLA Genetic Susceptibility in Rheumatoid Arthritis and Systemic Sclerosis. AB - BACKGROUND: Autoimmune diseases, including rheumatoid arthritis (RA) and systemic sclerosis (SSc) are characterized by a strong genetic susceptibility from the Human Leucocyte Antigen (HLA) locus. Additionally, disorders of epigenetic processes, in particular non-random X chromosome inactivation (XCI), have been reported in many female-predominant autoimmune diseases. Here we test the hypothesis that women with RA or SSc who are strongly genetically predisposed are less susceptible to XCI bias. METHODS: Using methylation sensitive genotyping of the androgen receptor (AR) gene, XCI profiles were performed in peripheral blood mononuclear cells from 161 women with RA, 96 women with SSc and 100 healthy women. HLA-DRB1 and DQB1 were genotyped. Presence of specific autoantibodies was documented for patients. XCI skewing was defined as having a ratio >= 80:20 of cells inactivating the same X chromosome. RESULTS: 110 women with RA, 68 women with SSc, and 69 controls were informative for the AR polymorphism. Among them 40.9% of RA patients and 36.8% of SSc patients had skewed XCI compared to 17.4% of healthy women (P = 0.002 and 0.018, respectively). Presence of RA susceptibility alleles coding for the "shared epitope" correlated with higher skewing among RA patients (P = 0.002) and such correlation was not observed in other women, healthy or with SSc. Presence of SSc-susceptibility alleles did not correlate with XCI patterns among SSc patients. CONCLUSION: Data demonstrate XCI skewing in both RA and SSc compared to healthy women. Unexpectedly, skewed XCI occurs more often in women with RA carrying the shared epitope, which usually reflects severe disease. This reinforces the view that loss of mosaicism in peripheral blood may be a consequence of chronic autoimmunity. PMID- 27355583 TI - RIDME distance measurements using Gd(iii) tags with a narrow central transition. AB - Methods based on pulse electron paramagnetic resonance allow measurement of the electron-electron dipolar coupling between two spin labels. Here we compare the most popular technique, Double Electron-Electron Resonance (DEER or PELDOR), with the dead-time free 5-pulse Relaxation-Induced Dipolar Modulation Enhancement (RIDME) method for Gd(iii)-Gd(iii) distance measurements at W-band (94.9 GHz, ~3.5 T) using Gd(iii) tags with a small zero field splitting (ZFS). Such tags are important because of their high EPR sensitivity arising from their narrow central transition. Two systems were investigated: (i) a rigid model compound with an inter-spin distance of 2.35 nm, and (ii) two mutants of a homodimeric protein, both labeled with a DOTA-based Gd(iii) chelate and characterized by an inter-spin distance of around 6 nm, one having a narrow distance distribution and the other a broad distribution. Measurements on the model compound show that RIDME is less sensitive to the complications arising from the failure of the weak coupling approximation which affect DEER measurements on systems characterized by short inter-spin distances between Gd(iii) tags having a narrow central transition. Measurements on the protein samples, which are characterized by a long inter-spin distance, emphasize the complications due to the appearance of harmonics of the dipolar interaction frequency in the RIDME traces for S > 1/2 spin systems, as well as enhanced uncertainties in the background subtraction. In both cases the sensitivity of RIDME was found to be significantly better than DEER. The effects of the experimental parameters on the RIDME trace are discussed. PMID- 27355584 TI - Role of Fimbriae, Flagella and Cellulose on the Attachment of Salmonella Typhimurium ATCC 14028 to Plant Cell Wall Models. AB - Cases of foodborne disease caused by Salmonella are frequently associated with the consumption of minimally processed produce. Bacterial cell surface components are known to be important for the attachment of bacterial pathogens to fresh produce. The role of these extracellular structures in Salmonella attachment to plant cell walls has not been investigated in detail. We investigated the role of flagella, fimbriae and cellulose on the attachment of Salmonella Typhimurium ATCC 14028 and a range of isogenic deletion mutants (DeltafliC fljB, DeltabcsA, DeltacsgA, DeltacsgA bcsA and DeltacsgD) to bacterial cellulose (BC)-based plant cell wall models [BC-Pectin (BCP), BC-Xyloglucan (BCX) and BC-Pectin-Xyloglucan (BCPX)] after growth at different temperatures (28 degrees C and 37 degrees C). We found that all three cell surface components were produced at 28 degrees C but only the flagella was produced at 37 degrees C. Flagella appeared to be most important for attachment (reduction of up to 1.5 log CFU/cm2) although both cellulose and fimbriae also aided in attachment. The csgD deletion mutant, which lacks both cellulose and fimbriae, showed significantly higher attachment as compared to wild type cells at 37 degrees C. This may be due to the increased expression of flagella-related genes which are also indirectly regulated by the csgD gene. Our study suggests that bacterial attachment to plant cell walls is a complex process involving many factors. Although flagella, cellulose and fimbriae all aid in attachment, these structures are not the only mechanism as no strain was completely defective in its attachment. PMID- 27355585 TI - Ancient Haplotypes at the 15q24.2 Microdeletion Region Are Linked to Brain Expression of MAN2C1 and Children's Intelligence. AB - The chromosome bands 15q24.1-15q24.3 contain a complex region with numerous segmental duplications that predispose to regional microduplications and microdeletions, both of which have been linked to intellectual disability, speech delay and autistic features. The region may also harbour common inversion polymorphisms whose functional and phenotypic manifestations are unknown. Using single nucleotide polymorphism (SNP) data, we detected four large contiguous haplotype-genotypes at 15q24 with Mendelian inheritance in 2,562 trios, African origin, high population stratification and reduced recombination rates. Although the haplotype-genotypes have been most likely generated by decreased or absent recombination among them, we could not confirm that they were the product of inversion polymorphisms in the region. One of the blocks was composed of three haplotype-genotypes (N1a, N1b and N2), which significantly correlated with intelligence quotient (IQ) in 2,735 children of European ancestry from three independent population cohorts. Homozygosity for N2 was associated with lower verbal IQ (2.4-point loss, p-value = 0.01), while homozygosity for N1b was associated with 3.2-point loss in non-verbal IQ (p-value = 0.0006). The three alleles strongly correlated with expression levels of MAN2C1 and SNUPN in blood and brain. Homozygosity for N2 correlated with over-expression of MAN2C1 over many brain areas but the occipital cortex where N1b homozygous highly under expressed. Our population-based analyses suggest that MAN2C1 may contribute to the verbal difficulties observed in microduplications and to the intellectual disability of microdeletion syndromes, whose characteristic dosage increment and removal may affect different brain areas. PMID- 27355586 TI - Trends in Mortality from Cerebrovascular and Hypertensive Diseases in Brazil Between 1980 and 2012. AB - BACKGROUND: Cerebrovascular and hypertensive diseases are among the main causes of death worldwide. However, there are limited data about the trends of these diseases over the years. OBJECTIVE: To evaluate the temporal trends in mortality rates and proportional mortality from cerebrovascular and hypertensive diseases according to sex and age in Brazil between 1980 and 2012. METHODS: We evaluated the underlying causes of death between 1980 and 2012 in both sexes and by age groups for circulatory diseases (CD), cerebrovascular diseases (CBVD), and hypertensive diseases (HD). We also evaluated death due to all causes (AC), external causes (EC), and ill-defined causes of death (IDCD). Data on deaths and population were obtained from the Department of Information Technology of the Unified Health System (Departamento de Informatica do Sistema Unico de Saude, DATASUS/MS). We estimated crude and standardized annual mortality rates per 100,000 inhabitants and percentages of proportional mortality rates. RESULTS: With the exception of EC, the mortality rates per 100,000 inhabitants of all other diseases increased with age. The proportional mortality of CD, CBVD, and HD increased up to the age range of 60-69 years in men and 70-79 years in women, and reached a plateau in both sexes after that. The standardized rates of CD and CBVD declined in both sexes. However, the HD rates showed the opposite trend and increased mildly during the study period. CONCLUSION: Despite the decline in standardized mortality rates due to CD and CBVD, there was an increase in deaths due to HD, which could be related to factors associated with the completion of the death certificates, decline in IDCD rates, and increase in the prevalence of hypertension. PMID- 27355587 TI - Low Prevalance of Major Events Adverse to Exercise Stress Echocardiography. AB - BACKGROUND: Stress echocardiography is well validated for diagnosis and risk stratification of coronary artery disease. Exercise stress echocardiography (ESE) has been shown to be the most physiological among the modalities of stress, but its safety is not well established. OBJECTIVE: To study the complications related to ESE and clinical and echocardiographic variables most commonly associated with their occurrence. METHODS: Cross-sectional study consisting of 10250 patients submitted to ESE for convenience, from January 2000 to June 2014. Cardiac Arrhythmias (CA) were the most frequent complications observed during the examination. The volunteers were divided into two groups according to the occurrence of CA during ESE: G1 group, composed of patients who have CA, and G2 formed by individuals who did not show such complication. RESULTS: Group G1, consisting of 2843 patients (27.7%), and Group G2 consisting of 7407 patients (72.3%). There was no death, acute myocardial infarction, ventricular fibrillation or asystole. Predominant CAs were: supraventricular extrasystoles (13.7%), and ventricular extrasystoles (11.5%). G1 group had a higher mean age, higher frequency of hypertension and smoking, larger aortic roots and left atrium (LA) and lower ejection fraction than G2. G1 group also had more ischemic changes (p < 0.001). The predictor variables were age (RR 1.04; [CI] 95% from 1.038 to 1.049) and LA (RR 1.64; [CI] 95% from 1.448 to 1.872). CONCLUSION: ESE proved to be a safe modality of stress, with non-fatal complications only. Advanced age and enlargement of the left atrium are predictive of cardiac arrhythmias. PMID- 27355588 TI - Cardiac Regeneration using Growth Factors: Advances and Challenges. AB - Myocardial infarction is the most significant manifestation of ischemic heart disease and is associated with high morbidity and mortality. Novel strategies targeting at regenerating the injured myocardium have been investigated, including gene therapy, cell therapy, and the use of growth factors. Growth factor therapy has aroused interest in cardiovascular medicine because of the regeneration mechanisms induced by these biomolecules, including angiogenesis, extracellular matrix remodeling, cardiomyocyte proliferation, stem-cell recruitment, and others. Together, these mechanisms promote myocardial repair and improvement of the cardiac function. This review aims to address the strategic role of growth factor therapy in cardiac regeneration, considering its innovative and multifactorial character in myocardial repair after ischemic injury. Different issues will be discussed, with emphasis on the regeneration mechanisms as a potential therapeutic resource mediated by growth factors, and the challenges to make these proteins therapeutically viable in the field of cardiology and regenerative medicine. Resumo O infarto do miocardio representa a manifestacao mais significativa da cardiopatia isquemica e esta associado a elevada morbimortalidade. Novas estrategias vem sendo investigadas com o intuito de regenerar o miocardio lesionado, incluindo a terapia genica, a terapia celular e a utilizacao de fatores de crescimento. A terapia com fatores de crescimento despertou interesse em medicina cardiovascular, devido aos mecanismos de regeneracao induzidos por essas biomoleculas, incluindo angiogenese, remodelamento da matriz extracelular, proliferacao de cardiomiocitos e recrutamento de celulas-tronco, dentre outros. Em conjunto, tais mecanismos promovem a reparacao do miocardio e a melhora da funcao cardiaca. Esta revisao pretende abordar o papel estrategico da terapia, com fatores de crescimento, para a regeneracao cardiaca, considerando seu carater inovador e multifatorial sobre o reparo do miocardio apos dano isquemico. Diferentes questoes serao discutidas, destacando-se os mecanismos de regeneracao como recurso terapeutico potencial mediado por fatores de crescimento e os desafios para tornar essas proteinas terapeuticamente viaveis no ambito da cardiologia e da medicina regenerativa. PMID- 27355579 TI - Correction: The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study. AB - [This corrects the article DOI: 10.1371/journal.pgen.1005378.]. PMID- 27355590 TI - Validity and Reliability Concerns Associated with Cardiopulmonary Exercise Testing Young People with Cystic Fibrosis. PMID- 27355589 TI - Effect of Age on Blood Rheology in Sickle Cell Anaemia and Sickle Cell Haemoglobin C Disease: A Cross-Sectional Study. AB - OBJECTIVES: Blood rheology plays a key role in the pathophysiology of sickle cell anaemia (SS) and sickle cell haemoglobin C disease (SC), but its evolution over the lifespan is unknown. MATERIALS AND METHODS: Blood viscosity, red blood cell (RBC) deformability and aggregation, foetal haemoglobin (HbF) and haematocrit were measured in 114 healthy individuals (AA), 267 SS (161 children + 106 adults) and 138 SC (74 children + 64 adults) patients. RESULTS: Our results showed that 1) RBC deformability is at its maximal value during the early years of life in SS and SC populations, mainly because HbF level is also at its peak, 2) during childhood and adulthood, hydroxycarbamide treatment, HbF level and gender modulated RBC deformability in SS patients, independently of age, 3) blood viscosity is higher in older SS and SC patients compared to younger ones and 4) haematocrit decreases as SS patients age. CONCLUSION: The hemorheological changes detected in older patients could play a role in the progressive development of several chronic disorders in sickle cell disease, whose prevalence increases with age. Retarding these age-related haemorheological impairments, by using suitable drugs, may minimize the risks of vaso-occlusive events and chronic disorders. PMID- 27355591 TI - Asymmetric Total Synthesis of Kopsiyunnanine K, a Monoterpenoid Indole Alkaloid with a Rearranged Skeleton. AB - A new monoterpenoid indole alkaloid, kopsiyunnanine K, was isolated from Kopsia arborea. Its intriguing rearranged structure and absolute configuration, which were inferred from spectral data and a possible biosynthetic pathway, were determined on the basis of a 13-step asymmetric total synthesis. PMID- 27355606 TI - Cognitive neuropsychology and its vicissitudes: The fate of Caramazza's axioms. AB - Cognitive neuropsychology is characterized as the discipline in which one draws conclusions about the organization of the normal cognitive systems from the behaviour of brain-damaged individuals. In a series of papers, Caramazza, later in collaboration with McCloskey, put forward four assumptions as the bridge principles for making such inferences. Four potential pitfalls, one for each axiom, are discussed with respect to the use of single-case methods. Two of the pitfalls also apply to case series and group study procedures, and the other two are held to be indirectly testable or avoidable. Moreover, four other pitfalls are held to apply to case series or group study methods. It is held that inferences from single-case procedures may profitably be supported or rejected using case series/group study methods, but also that analogous support needs to be given in the other direction for functionally based case series or group studies. It is argued that at least six types of neuropsychological method are valuable for extrapolation to theories of the normal cognitive system but that the single- or multiple-case study remains a critical part of cognitive neuropsychology's methods. PMID- 27355607 TI - Declining object recognition performance in semantic dementia: A case for stored visual object representations. AB - The role of the semantic system in recognizing objects is a matter of debate. Connectionist theories argue that it is impossible for a participant to determine that an object is familiar to them without recourse to a semantic hub; localist theories state that accessing a stored representation of the visual features of the object is sufficient for recognition. We examine this issue through the longitudinal study of two cases of semantic dementia, a neurodegenerative disorder characterized by a progressive degradation of the semantic system. The cases in this paper do not conform to the "common" pattern of object recognition performance in semantic dementia described by Rogers, T. T., Lambon Ralph, M. A., Hodges, J. R., & Patterson, K. (2004). Natural selection: The impact of semantic impairment on lexical and object decision. Cognitive Neuropsychology, 21, 331 352., and show no systematic relationship between severity of semantic impairment and success in object decision. We argue that these data are inconsistent with the connectionist position but can be easily reconciled with localist theories that propose stored structural descriptions of objects outside of the semantic system. PMID- 27355608 TI - Simulation of impairment: Commentary on Nickels, Rapp, and Kohnen (2015). AB - Nickels, L., Rapp, B., and Kohnen, S. (2015. Challenges in the use of treatment to investigate cognition. Cognitive Neuropsychology, 32, 91-103) argue that impairment and treatment may be used to test computational models of cognition. They state that, contrary to their view, the authors of the WEAVER++ model of spoken word production have explicitly rejected simulation of impairment [i.e., Levelt, W. J. M., Roelofs, A., & Meyer, A. S. (1999b). Multiple perspectives on word production. Behavioral and Brain Sciences, 22, 61-69]. Here, I argue that this incorrectly characterizes the position of Levelt et al. Moreover, I further clarify this position, which holds that simulation of impairment requires both a theory of the intact system and assumptions about the underlying deficit, which is a widely accepted view. To demonstrate this position, I outline the approach taken in WEAVER++ simulations of aphasic performance reported in Roelofs, A. (2014. A dorsal-pathway account of aphasic language production: The WEAVER++/ARC model. Cortex, 59, 33-48). These simulations not only prove that the developers of WEAVER++ endorse simulation of impairment, but also highlight the importance of integrating psycholinguistic, functional neuroimaging, and tractographic evidence in testing models of impaired performance. PMID- 27355609 TI - Nonlinear spelling in graphemic buffer deficit. AB - In this paper, we describe a case of nonlinear spelling and its implications for theories of the graphemic buffer. C.T.J., an individual with an acquired deficit of the graphemic buffer, often wrote the letters of his responses in a nonlinear temporal order when writing to dictation. The spatial ordering of the letters was maintained: Letters in the later positions of the words were written towards the right side of the response, even when written before letters in earlier positions. This unusual phenomenon has been briefly reported in three prior cases but this study provides the most detailed analysis of the phenomenon to date. We specifically contend that the decoupling of the temporal and spatial aspects of spelling is difficult to reconcile with competitive queuing accounts of the graphemic buffer. PMID- 27355612 TI - Validation of Three Platelet Function Tests for Bleeding Risk Stratification During Dual Antiplatelet Therapy Following Coronary Interventions. AB - BACKGROUND: Although low platelet reactivity (LPR) is commonly detected during bleeding, a validated threshold for reliable DAPT bleeding risk stratification is lacking. We tested the diagnostic utility of 3 conventional platelet-activity assays to define the predictive value (if any) of LPR for bleeding. HYPOTHESIS: We hypothesized whether one of these tests be better than any others for predicting bleeding events. METHODS: Patients (n = 800) following drug-eluting stent implantation received DAPT. Bleeding was assessed by Bleeding Academic Research Consortium (BARC) classification and events were collected for 1 year after stenting. Platelet reactivity was measured by light transmittance aggregometry (LTA), VerifyNow, and multiple electrode aggregometry (MEA). The LPR values for bleeding event stratification were defined as <=15% for LTA, <=139 PRU for VerifyNow, and <=25 U for MEA. RESULTS: Bleeding events occurred in 18 patients (2.3%). All tests distinguished LPR as an independent predictor for bleeding by univariate analysis ([HR]: 5.00, 95% [CI]: 1.8-14.0, P = 0.002 for LTA; HR: 21.3, 95% CI: 6.2-73.0, P < 0.0001 for VerifyNow; and HR: 7.4, 95% CI: 2.2-25.5, P = 0.002 for MEA). Multivariate analysis revealed that only VerifyNow (HR: 11.5, 95% CI: 2.9-45.7, P < 0.0004) remained an independent predictor for bleeding. However, the specificity (81.5%, 60.2%, and 81.7%, respectively) and sensitivity (61.1%, 83.3%, and 83.2%, respectively) of all 3 tests were quite low. CONCLUSIONS: Among 3 conventional platelet-activity assays, VerifyNow was better than LTA or MEA for triaging future bleeding risks. However, all 3 tests failed to reliably predict future bleeding. PMID- 27355613 TI - Size-dependent, stochastic nature of lipid exchange between nano-vesicles and model membranes. AB - The interaction of nanoscale lipid vesicles with cell membranes is of fundamental importance for the design and development of vesicular drug delivery systems. Here, we introduce a novel approach to study vesicle-membrane interactions whereby we are able to probe the influence of nanoscale membrane properties on the dynamic adsorption, exchange, and detachment of vesicles. Using total internal reflection fluorescence (TIRF) microscopy, we monitor these processes in real-time upon the electrostatically tuned attachment of individual, sub-100 nm vesicles to a supported lipid bilayer. The observed exponential vesicle detachment rate depends strongly on the vesicle size, but not on the vesicle charge, which suggests that lipid exchange occurs during a single stochastic event, which is consistent with membrane stalk formation. The fluorescence microscopy assay developed in this work may enable measuring of the probability of stalk formation in a controlled manner, which is of fundamental importance in membrane biology, offering a new tool to understand nanoscale phenomena in the context of biological sciences. PMID- 27355615 TI - Time-Resolved X-ray Scattering and Raman Spectroscopic Studies of Formation of a Uranium-Vanadium-Phosphorus-Peroxide Cage Cluster. AB - Combining reactants in water under ambient conditions results in the assembly and crystallization of 2.6 nm diameter cage clusters designated U48V6P48 within 3 weeks. These consist of 24 uranyl hexagonal bipyramids, 24 uranyl pentagonal bipyramids, six vanadyl square pyramids, and 48 phosphate tetrahedra. Peroxide bridged dimers of uranyl hexagonal bipyramids are linked directly to vanadyl stabilized tetramers of uranyl pentagonal bipyramids to form the cage, with phosphate tetrahedra providing additional linkages between these two units. Time resolved small-angle X-ray scattering and Raman spectroscopy indicate that the combination of the reactants initially resulted in simultaneous formation of smaller uranyl peroxide cages and vanadyl peroxide complexes. The disappearance of the smaller uranyl peroxide cages from solution coincides with the diminution of uncoordinated peroxide, both of which occurred before the assembly of the relatively peroxide-poor U48V6P48, which clearly occurred in solution prior to its crystallization. PMID- 27355614 TI - In vivo super-resolution RESOLFT microscopy of Drosophila melanogaster. AB - Despite remarkable developments in diffraction unlimited super-resolution microscopy, in vivo nanoscopy of tissues and model organisms is still not satisfactorily established and rarely realized. RESOLFT nanoscopy is particularly suited for live cell imaging because it requires relatively low light levels to overcome the diffraction barrier. Previously, we introduced the reversibly switchable fluorescent protein rsEGFP2, which facilitated fast RESOLFT nanoscopy (Grotjohann et al., 2012). In that study, as in most other nanoscopy studies, only cultivated single cells were analyzed. Here, we report on the use of rsEGFP2 for live-cell RESOLFT nanoscopy of sub-cellular structures of intact Drosophila melanogaster larvae and of resected tissues. We generated flies expressing fusion proteins of alpha-tubulin and rsEGFP2 highlighting the microtubule cytoskeleton in all cells. By focusing through the intact larval cuticle, we achieved lateral resolution of. PMID- 27355619 TI - Progressive Resistance Training in End-Stage Renal Disease: Systematic Review. AB - BACKGROUND: This systematic review provides an overview of the extant literature on progressive resistance training (PRT) in patients with end-stage renal disease (ESRD) and outlines recommendations for future trials. METHODS: A systematic review of all published literature evaluating the chronic (>6 weeks) application of PRT in patients with ESRD using electronic databases. RESULTS: The search yielded 16 clinical trials, including 11 randomized controlled trials (RCT), 4 uncontrolled trials and one trial involving a within-subjects control period plus RCT. RCT quality, assessed via the CONSORT statement, ranged from low (4/10) to high (10/10) with a mean score of 7.3/10; 7/11 RCT had a quality score >=7.5. All trials evaluated chronic adaptation to PRT across a range of important outcomes. PRT can induce muscle hypertrophy and improve aspects of physical functioning and health-related quality of life in ESRD. There is preliminary evidence that PRT may reduce protein-energy malnutrition and cardiovascular disease risk factors, including C-reactive protein, total cholesterol, triglyceride, and measures of insulin resistance in patients with or at-risk of comorbid type 2 diabetes. The evidence base for PRT adapting some of the endpoints investigated to date remains inconsistent (e.g. physical performance tests, obesity outcomes), and many other pertinent clinical outcomes remain to be investigated. CONCLUSION: RCT are required to investigate a range of novel research questions related to the benefits and application of PRT in this cohort and its patient subgroups (e.g. diabetes, depression, dyslipidemia, etc.). Future studies must be of high methodological quality to inform clinical practice guidelines. PMID- 27355616 TI - The relation of female circumcision to sexual behavior in Kenya and Nigeria. AB - One of the reasons for the perpetuation of female circumcision is that it controls female sexuality. In this study, the authors examined the relationship between female circumcision and the sexual behavior of women in Kenya and Nigeria. Data on women who were aware of circumcision and were circumcised were extracted from the Kenya Demographic and Health Survey of 2008-09 as well as the Nigeria Demographic and Health Survey of 2008. The sample size was 7,344 for Kenya and 16,294 for Nigeria. The outcome variables were age at first intercourse and total lifetime number of sexual partners. The study hypothesis was that women who were circumcised were less likely to have initiated sex early and to have only one sex partner. Cox proportional hazards regression and Poisson regression were used to examine the relations of female circumcision and other selected variables to sexual behavior. No association was observed between female circumcision and the outcomes for sexual behavior of women in Kenya and Nigeria. The argument of sexual chastity is insufficient to sustain the perpetuation of female circumcision. PMID- 27355621 TI - The "Next Big Thing" in Treatment for Relapsed or Refractory Multiple Myeloma May Be Held Back by Design-Between the Lines. PMID- 27355620 TI - Performance Testing of PCR Assay in Blood Samples for the Diagnosis of Toxoplasmic Encephalitis in AIDS Patients from the French Departments of America and Genetic Diversity of Toxoplasma gondii: A Prospective and Multicentric Study. AB - BACKGROUND: Toxoplasmic encephalitis in patients with AIDS is a life-threatening disease mostly due to reactivation of Toxoplasma gondii cysts in the brain. The main objective of this study was to evaluate the performance of real-time PCR assay in peripheral blood samples for the diagnosis of toxoplasmic encephalitis in AIDS patients in the French West Indies and Guiana. METHODOLOGY/PRINCIPAL FINDINGS: Adult patients with HIV and suspicion of toxoplasmic encephalitis with start of specific antitoxoplasmic therapy were included in this study during 40 months. The real-time PCR assay targeting the 529 bp repeat region of T. gondii was performed in two different centers for all blood samples. A Neighbor-Joining tree was reconstructed from microsatellite data to examine the relationships between strains from human cases of toxoplasmosis in South America and the Caribbean. A total of 44 cases were validated by a committee of experts, including 36 cases with toxoplasmic encephalitis. The specificity of the PCR assay in blood samples was 100% but the sensitivity was only 25% with moderate agreement between the two centers. Altered level of consciousness and being born in the French West Indies and Guiana were the only two variables that were associated with significantly decreased risk of false negative results with the PCR assay. CONCLUSION/SIGNIFICANCE: Our results showed that PCR sensitivity in blood samples increased with severity of toxoplasmic encephalitis in AIDS patients. Geographic origin of patients was likely to influence PCR sensitivity but there was little evidence that it was caused by differences in T. gondii strains. TRIAL REGISTRATION: ClinicalTrials.gov NCT00803621. PMID- 27355623 TI - Low field magnetoresistance in a 2D topological insulator based on wide HgTe quantum well. AB - Low field magnetoresistance is experimentally studied in a two-dimensional topological insulator (TI) in both diffusive and quasiballistic samples fabricated on top of a wide (14 nm) HgTe quantum well. In all cases a pronounced quasi-linear positive magnetoresistance is observed similar to that found previously in diffusive samples based on a narrow (8 nm) HgTe well. The experimental results are compared with the main existing theoretical models based on different types of disorder: sample edge roughness, nonmagnetic disorder in an otherwise coherent TI and metallic puddles due to locally trapped charges that act like local gate on the sample. The quasiballistic samples with resistance close to the expected quantized values also show a positive low-field magnetoresistance but with a pronounced admixture of mesoscopic effects. PMID- 27355622 TI - Strain Differences in Light-Induced Retinopathy. AB - The purpose of this study was to better understand the role of ocular pigmentation and genetics in light-induced retinal damage. Adult pigmented [Long Evans (LE) and Brown Norway (BN)] and albino [Sprague Dawley (SD) and Lewis (LW)] rats were exposed to a bright cyclic light for 6 consecutive days and where compared with juvenile animals exposed to the same bright light environment from postnatal age 14 to 28. Flash ERGs and retinal histology were performed at predetermined days (D) post-light exposure. At D1, ERGs were similar in all adult groups with no recordable a-waves and residual b-waves. A transient recovery was noticed at D30 in the LW and LE only [b-wave: 18% and 25% of their original amplitude respectively]. Histology revealed that BN retina was the most damaged, while LE retina was best preserved. SD and LW rats were almost as damaged as BN rats. In contrast, the retina of juvenile BN was almost as resistant to the bright light exposure as that of juvenile LE rats. Our results strongly suggest that, although ocular pigmentation and genetic background are important factors in regulating the severity of light-induced retinal damage, the age of the animal at the onset of light exposure appears to be the most important determining factor. PMID- 27355624 TI - Height Outcome of Recombinant Human Growth Hormone Treatment in Achondroplasia Children: A Meta-Analysis. AB - BACKGROUND/AIMS: Although recombinant human growth hormone (rhGH) is not approved to treat short stature of achondroplasia (ACH), some studies suggested growth improvement during short-term rhGH treatment. METHODS: A meta-analysis of rhGH therapy efficacy in ACH children was performed. RESULTS: From 12 English-language studies, 558 (54.0% males) rhGH-treated ACH children were enrolled. Administration of rhGH (median dosage 0.21 mg/kg/ week; range 0.16-0.42 mg/kg/week) improved height (Ht) from baseline [-5.069 standard deviation score (SDS; 95% CI -5.109 to -5.029); p < 0.0001] to 12 [-4.325 SDS (95% CI -4.363 to 4.287); p < 0.0001] and 24 months [-4.073 SDS (95% CI -4.128 to -4.019); p < 0.0001]. Then, Ht remained approximately constant up to 5 years [-3.941 SDS (95% CI -4.671 to -3.212); p < 0.0001]. CONCLUSIONS: In ACH children, rhGH treatment increased Ht from -5.0 to -4.0 SDS during 5 years, but insufficient data are available on both the adult Ht and the changes of body proportions. PMID- 27355625 TI - Pyrosequencing Unveils Cystic Fibrosis Lung Microbiome Differences Associated with a Severe Lung Function Decline. AB - Chronic airway infection is a hallmark feature of cystic fibrosis (CF) disease. In the present study, sputum samples from CF patients were collected and characterized by 16S rRNA gene-targeted approach, to assess how lung microbiota composition changes following a severe decline in lung function. In particular, we compared the airway microbiota of two groups of patients with CF, i.e. patients with a substantial decline in their lung function (SD) and patients with a stable lung function (S). The two groups showed a different bacterial composition, with SD patients reporting a more heterogeneous community than the S ones. Pseudomonas was the dominant genus in both S and SD patients followed by Staphylococcus and Prevotella. Other than the classical CF pathogens and the most commonly identified non-classical genera in CF, we found the presence of the unusual anaerobic genus Sneathia. Moreover, the oligotyping analysis revealed the presence of other minor genera described in CF, highlighting the polymicrobial nature of CF infection. Finally, the analysis of correlation and anti-correlation networks showed the presence of antagonism and ecological independence between members of Pseudomonas genus and the rest of CF airways microbiota, with S patients showing a more interconnected community in S patients than in SD ones. This population structure suggests a higher resilience of S microbiota with respect to SD, which in turn may hinder the potential adverse impact of aggressive pathogens (e.g. Pseudomonas). In conclusion, our findings shed a new light on CF airway microbiota ecology, improving current knowledge about its composition and polymicrobial interactions in patients with CF. PMID- 27355627 TI - Plasma Mitochondrial DNA Level is a Prognostic Marker in Peritoneal Dialysis Patients. AB - BACKGROUND/AIMS: Circulating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that circulating mitochondrial DNA, which has a similar structure with bacterial DNA, correlates with systemic inflammatory state and predicts cardiovascular event in new PD patients. METHODS: We measured plasma mitochondrial DNA level by quantitative polymerase chain reaction (PCR) in 197 new PD patients and 150 patients with chronic kidney disease. PD patients were followed for 24 months for the development of cardiovascular event, hospitalization, and patient survival. RESULTS: There was a stepwise increase in plasma mitochondrial DNA level with worsening renal function. The average plasma mitochondrial DNA level was 18.0 +/- 1.2 PCR cycles. Plasma mitochondrial DNA level correlated with serum CRP level (r = -0.538, p < 0.0001). At 24 months, the event-free survival was 67.4%, 66.4%, 63.4% and 44.2% for plasma mitochondrial DNA level quartiles I, II, III and IV, respectively (p = 0.049). After adjusting for confounders, plasma mitochondrial DNA level, malnutrition-inflammation score, and baseline arterial pulse wave velocity were independent predictors of composite cardiovascular end-point; each doubling in plasma mitochondrial DNA level confers 16.0% (95% confidence interval, 2.5 - 31.3%, p = 0.001) excess in risk. Plasma mitochondrial DNA also correlated with the number of hospital admission (r = -0.218, p = 0.002) and duration of hospitalization for cardiovascular reasons (r = -0.232, p = 0.001). CONCLUSION: Plasma mitochondrial DNA level significantly correlates with systemic inflammatory state, and is a strong predictor of cardiovascular event as well as the need of hospitalization in new PD patients. PMID- 27355626 TI - Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis. AB - BACKGROUND: HIV transmitted drug resistance (TDR) remains at moderate level in Latin America and the Caribbean (LAC). However, different epidemiologic scenarios could influence national and sub-regional TDR levels and trends. METHODS AND FINDINGS: We performed a systematic review of currently available publications on TDR in antiretroviral treatment-naive adults in LAC. Ninety-eight studies published between January 2000 and June 2015 were included according to critical appraisal criteria and classified by sub-region: Brazil (50), Mesoamerica (17), Southern Cone (16), Andean (8) and Caribbean (7). From these, 81 studies encompassing 11,441 individuals with data on DR mutation frequency were included in a meta-analysis. Overall TDR prevalence in LAC was 7.7% (95% CI: 7.2%-8.2%). An increasing trend was observed for overall TDR when comparing 2000-2005 (6.0%) and 2006-2015 (8.2%) (p<0.0001), which was associated with significant NNRTI TDR increase (p<0.0001). NRTI TDR decreased (4.5% vs. 2.3%, p<0.0001). NNRTI TDR increase was associated mainly with K101E, K103N and G190A. NRTI TDR decrease was associated mainly with M184V, K70R and T215Y. All sub-regions reached moderate overall TDR levels. The rapid increase in TDR to all antiretroviral classes in the Caribbean is notable, as well as the significant increase in NNRTI TDR reaching moderate levels in the Southern Cone. NRTI TDR was dominant in 2000 2005, mainly in the Caribbean, Mesoamerica and Brazil. This dominance was lost in 2006-2015 in all sub-regions, with the Southern Cone and the Caribbean switching to NNRTI dominance. PI TDR remained mostly constant with a significant increase only observed in the Caribbean. CONCLUSIONS: Given the high conceptual and methodological heterogeneity of HIV TDR studies, implementation of surveys with standardized methodology and national representativeness is warranted to generate reliable to inform public health policies. The observed increasing trend in NNRTI TDR supports the need to strengthen TDR surveillance and programme monitoring and evaluation in LAC. PMID- 27355628 TI - Temporal Changes in BEXSERO(r) Antigen Sequence Type Associated with Genetic Lineages of Neisseria meningitidis over a 15-Year Period in Western Australia. AB - Neisseria meningitidis is the causative agent of invasive meningococcal disease (IMD). The BEXSERO(r) vaccine which is used to prevent serogroup B disease is composed of four sub-capsular protein antigens supplemented with an outer membrane vesicle. Since the sub-capsular protein antigens are variably expressed and antigenically variable amongst meningococcal isolates, vaccine coverage can be estimated by the meningococcal antigen typing system (MATS) which measures the propensity of the strain to be killed by vaccinated sera. Whole genome sequencing (WGS) which identifies the alleles of the antigens that may be recognised by the antibody response could represent, in future, an alternative estimate of coverage. In this study, WGS of 278 meningococcal isolates responsible for 62% of IMD in Western Australia from 2000-2014 were analysed for association of genetic lineage (sequence type [ST], clonal complex [cc]) with BEXSERO(r) antigen sequence type (BAST) and MATS to predict the annual vaccine coverage. A hyper endemic period of IMD between 2000-05 was caused by cc41/44 with the major sequence type of ST-146 which was not predicted by MATS or BAST to be covered by the vaccine. An increase in serogroup diversity was observed between 2010-14 with the emergence of cc11 serogroup W in the adolescent population and cc23 serogroup Y in the elderly. BASTs were statistically associated with clonal complex although individual antigens underwent antigenic drift from the major type. BAST and MATS predicted an annual range of 44-91% vaccine coverage. Periods of low vaccine coverage in years post-2005 were not a result of the resurgence of cc41/44:ST-146 but were characterised by increased diversity of clonal complexes expressing BASTs which were not predicted by MATS to be covered by the vaccine. The driving force behind the diversity of the clonal complex and BAST during these periods of low vaccine coverage is unknown, but could be due to immune selection and inter-strain competition with carriage of non-disease causing meningococci. PMID- 27355629 TI - Characterisation of Transcriptional Changes in the Spinal Cord of the Progressive Experimental Autoimmune Encephalomyelitis Biozzi ABH Mouse Model by RNA Sequencing. AB - Multiple sclerosis (MS) is a debilitating immune-mediated neurological disorder affecting young adults. MS is primarily relapsing-remitting, but neurodegeneration and disability accumulate from disease onset. The most commonly used mouse MS models exhibit a monophasic immune response with fast accumulation of neurological damage that does not allow the study of progressive neurodegeneration. The chronic relapsing and secondary progressive EAE (pEAE) Biozzi ABH mouse model of MS exhibits a reproducible relapsing-remitting disease course that slowly accumulates permanent neurological deficit and develops a post relapsing progressive disease that permits the study of demyelination and neurodegeneration. RNA sequencing (RNAseq) was used to explore global gene expression in the pEAE Biozzi ABH mouse. Spinal cord tissue RNA from pEAE Biozzi ABH mice and healthy age-matched controls was sequenced. 2,072 genes were differentially expressed (q<0.05) from which 1,397 were significantly upregulated and 675 were significantly downregulated. This hypothesis-free investigation characterised the genomic changes that describe the pEAE mouse model. The differentially expressed genes revealed a persistent immunoreactant phenotype, combined with downregulation of the cholesterol biosynthesis superpathway and the LXR/RXR activation pathway. Genes differentially expressed include the myelination genes Slc17a7, Ugt8A and Opalin, the neuroprotective genes Sprr1A, Osm and Wisp2, as well as genes identified as MS risk factors, including RGs14 and Scap2. Novel genes with unestablished roles in EAE or MS were also identified. The identification of differentially expressed novel genes and genes involved in MS pathology, opens the door to their functional study in the pEAE mouse model which recapitulates some of the important clinical features of progressive MS. PMID- 27355631 TI - [Gastrointestinal complications in hematological patients]. PMID- 27355632 TI - [Not Available]. PMID- 27355630 TI - Gene-Expression Profiling Suggests Impaired Signaling via the Interferon Pathway in Cstb-/- Microglia. AB - Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1, OMIM254800) is an autosomal recessive neurodegenerative disorder characterized by stimulus sensitive and action-activated myoclonus, tonic-clonic epileptic seizures, and ataxia. Loss-of-function mutations in the gene encoding the cysteine protease inhibitor cystatin B (CSTB) underlie EPM1. The deficiency of CSTB in mice (Cstb-/ mice) generates a phenotype resembling the symptoms of EPM1 patients and is accompanied by microglial activation at two weeks of age and an upregulation of immune system-associated genes in the cerebellum at one month of age. To shed light on molecular pathways and processes linked to CSTB deficiency in microglia we characterized the transcriptome of cultured Cstb-/- mouse microglia using microarray hybridization and RNA sequencing (RNA-seq). The gene expression profiles obtained with these two techniques were in good accordance and not polarized to either pro- or anti-inflammatory status. In Cstb-/- microglia, altogether 184 genes were differentially expressed. Of these, 33 genes were identified by both methods. Several interferon-regulated genes were weaker expressed in Cstb-/- microglia compared to control. This was confirmed by quantitative real-time PCR of the transcripts Irf7 and Stat1. Subsequently, we explored the biological context of CSTB deficiency in microglia more deeply by functional enrichment and canonical pathway analysis. This uncovered a potential role for CSTB in chemotaxis, antigen-presentation, and in immune- and defense response-associated processes by altering JAK-STAT pathway signaling. These data support and expand the previously suggested involvement of inflammatory processes to the disease pathogenesis of EPM1 and connect CSTB deficiency in microglia to altered expression of interferon-regulated genes. PMID- 27355633 TI - [Not Available]. PMID- 27355634 TI - [Not Available]. PMID- 27355635 TI - [Not Available]. PMID- 27355636 TI - [Not Available]. PMID- 27355637 TI - [Not Available]. PMID- 27355638 TI - [Not Available]. PMID- 27355639 TI - [Not Available]. PMID- 27355640 TI - [Not Available]. PMID- 27355641 TI - [Not Available]. PMID- 27355642 TI - [Not Available]. PMID- 27355643 TI - [Not Available]. PMID- 27355644 TI - [Not Available]. PMID- 27355645 TI - Effects of Episodic Future Thinking and Self-Projection on Children's Prospective Memory Performance. AB - The present study is the first to investigate the benefits of episodic future thinking (EFT) at encoding on prospective memory (PM) in preschool (age: M = 66.34 months, SD = 3.28) and primary school children (age: M = 88.36 months, SD = 3.12). A second aim was to examine if self-projection influences the possible effects of EFT instructions. PM was assessed using a standard PM paradigm in children with a picture-naming task as the ongoing activity in which the PM task was embedded. Further, two first- and two second-order ToM tasks were administered as indicator of children's self-projection abilities. Forty-one preschoolers and 39 school-aged children were recruited. Half of the participants in each age group were instructed to use EFT as a strategy to encode the PM task, while the others received standard PM instructions. Results revealed a significant age effect, with school-aged children significantly outperforming preschoolers and a significant effect of encoding condition with overall better performance when receiving EFT instructions compared to the standard encoding condition. Even though the interaction between age group and encoding condition was not significant, planned comparisons revealed first evidence that compared to the younger age group, older children's PM benefitted more from EFT instructions during intention encoding. Moreover, results showed that although self-projection had a significant impact on PM performance, it did not influence the effects of EFT instructions. Overall, results indicate that children can use EFT encoding strategies to improve their PM performance once EFT abilities are sufficiently developed. Further, they provide first evidence that in addition to executive functions, which have already been shown to influence the development of PM across childhood, self-projection seems to be another key mechanism underlying this development. PMID- 27355646 TI - Anterior Lamina Cribrosa Surface Depth in Open-Angle Glaucoma: Relationship with the Position of the Central Retinal Vessel Trunk. AB - PURPOSE: To determine the factors influencing the anterior lamina cribrosa (LC) surface depth (LCD) in patients with open-angle glaucoma (OAG), focusing on the association between LCD and the position of the central retinal vessel trunk (CRVT) at the anterior LC surface. METHODS: Optic nerve heads of 205 OAG eyes were scanned using swept-source optical coherence tomography (SS-OCT). After processing the images using adaptive compensation, the LCD was determined from 11 horizontal B-scan images that divided the optic disc vertically into 12 equal parts. Eyes were divided into two groups (central or peripheral) according to where the CRVT exits from the anterior LC surface. The influence of CRVT position on LCD was evaluated, taking into account age, gender, untreated intraocular pressure (IOP), IOP at optic-disc scanning, retinal nerve fiber layer (RNFL) thickness, visual-field mean deviation, central corneal thickness, and axial length. RESULTS: Patients in the peripheral CRVT group were younger and more myopic, and had a larger mean LCD and thinner global RNFL than those in the central CRVT group (all P<=0.023). On multivariate analysis, the peripheral CRVT location was significantly associated with a larger LCD (P = 0.002), together with the significant association of younger age (P<0.001), higher untreated IOP (P = 0.010), and thinner RNFL (P = 0.003) on the larger LCD. CONCLUSION: In OAG, CRVT location was an independent factor influencing the LCD, together with age, untreated IOP, and global RNFL thickness. The data indicate that the CRVT may contribute to the resistance of the LC against deformation. A longitudinal prospective observation is required to clarify this relationship. PMID- 27355648 TI - Identification and Mechanistic Studies of a Cell Cycle Regulator JP18 from a Library of Synthetic Indole Terpenoid Mimics. AB - We constructed a small library of indole terpenoid mimics using a hybridizing strategy to link various indole and alpha,beta-unsaturated enone building blocks together. Prepared compounds were evaluated for the cytotoxicity against a panel of cancer cell lines. An indolyl ketone called JP18 was identified as a cell cycle regulator, and the underlying mechanism was investigated. PMID- 27355647 TI - Dietary Carbohydrates and Childhood Functional Abdominal Pain. AB - Childhood functional gastrointestinal disorders (FGIDs) affect a large number of children throughout the world. Carbohydrates (which provide the majority of calories consumed in the Western diet) have been implicated both as culprits for the etiology of symptoms and as potential therapeutic agents (e.g., fiber) in childhood FGIDs. In this review, we detail how carbohydrate malabsorption may cause gastrointestinal symptoms (e.g., bloating) via the physiologic effects of both increased osmotic activity and increased gas production from bacterial fermentation. Several factors may play a role, including: (1) the amount of carbohydrate ingested; (2) whether ingestion is accompanied by a meal or other food; (3) the rate of gastric emptying (how quickly the meal enters the small intestine); (4) small intestinal transit time (the time it takes for a meal to enter the large intestine after first entering the small intestine); (5) whether the meal contains bacteria with enzymes capable of breaking down the carbohydrate; (6) colonic bacterial adaptation to one's diet, and (7) host factors such as the presence or absence of visceral hypersensitivity. By detailing controlled and uncontrolled trials, we describe how there is a general lack of strong evidence supporting restriction of individual carbohydrates (e.g., lactose, fructose) for childhood FGIDs. We review emerging evidence suggesting that a more comprehensive restriction of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) may be effective. Finally, we review how soluble fiber (a complex carbohydrate) supplementation via randomized controlled intervention trials in childhood functional gastrointestinal disorders has demonstrated efficacy. PMID- 27355650 TI - Real-Time Prediction for Burn Length of Stay Via Median Residual Hospital Length of Stay Methodology. AB - Hospital length of stay (LOS) after burn injury is commonly estimated as 1 day per percent burn, but LOS often exceeds that estimate. The purpose of this study is to develop a novel method for estimating burn hospital LOS at any time during hospitalization. The authors used the American Burn Association National Burn Repository from 2000 to 2009 to directly estimate the median residual LOS (MRLOS) of patients hospitalized for burn injuries and who survived to discharge. The MRLOS is the median of how many more days a burn patient will be hospitalized given that the person has been in hospital for a specified time period. The authors also estimated the 25th and 75th percentiles of residual life and quantified the relationship between MRLOS and LOS with ordinary least squares for all burn patients, by burn size and by presence of inhalation injury. MRLOS increased with increasing LOS, confirming that discharge estimates change over time. Patients with inhalation injury had longer MRLOS than patients without inhalation injury in the first 100 hospital days. Patients with large burns (>25%) had large MRLOS consistent with prolonged hospitalization, but patients with small burns (<25%) also had steadily increasing MRLOS during hospitalization (ie, the longer the patient was in the hospital, the longer the predicted LOS regardless of initial LOS estimate). Estimating remaining hospital LOS at any time during admission has been problematic; MRLOS can be used to provide an estimate of remaining hospital LOS and resource utilization to families, administrators, and other medical professionals. PMID- 27355651 TI - Modified Meek Micrografting Technique for Wound Coverage in Extensive Burn Injuries. AB - The modified Meek micrografting technique constitutes a rapid and efficient surgical approach for the skin coverage of extensive full-thickness burn injuries. A total of 10 burn patients (mean 68 +/- 9.2% TBSA) admitted to our burn unit required one or more Meek micrografting procedures (mean 2.2 +/- 0.5) to cover in average 43.4 +/- 11.6% TBSA (range between 10 and 75% TBSA). This goal was achieved using a donor site area ranging between 2.5 and 18% TBSA. All patients developed local infection to Pseudomona aeruginosa (75%), Stenotrophomona maltophilia (25%), methicillin-resistant Staphylococcus aureus (12.5%), and Acinetobacter baumannii (12.5%). Thus, the average of Meek regrafting after graft-take failure was 13.1 +/- 6.4% TBSA (median: 9%; range from 0 to 36%). The period to obtain stable definitive wound closure was in average of 67.2 +/- 21 days post injury. The modified Meek micrografting provides a reliable and versatile method for the coverage of large burn wounds with limited autograft donor sites and is now routinely used in our institution. Its systematic use improves operating times and overall outcomes reducing the number of surgeries, increasing the percentage of graft take, and decreasing the length of stay. PMID- 27355652 TI - Invasive Aspergillus Infection Leading to Vascular Thrombosis and Amputation in a Severely Burned Child. PMID- 27355649 TI - Is Butter Back? A Systematic Review and Meta-Analysis of Butter Consumption and Risk of Cardiovascular Disease, Diabetes, and Total Mortality. AB - BACKGROUND: Dietary guidelines recommend avoiding foods high in saturated fat. Yet, emerging evidence suggests cardiometabolic benefits of dairy products and dairy fat. Evidence on the role of butter, with high saturated dairy fat content, for total mortality, cardiovascular disease, and type 2 diabetes remains unclear. We aimed to systematically review and meta-analyze the association of butter consumption with all-cause mortality, cardiovascular disease, and diabetes in general populations. METHODS AND FINDINGS: We searched 9 databases from inception to May 2015 without restriction on setting, or language, using keywords related to butter consumption and cardiometabolic outcomes. Prospective cohorts or randomized clinical trials providing estimates of effects of butter intake on mortality, cardiovascular disease including coronary heart disease and stroke, or diabetes in adult populations were included. One investigator screened titles and abstracts; and two reviewed full-text articles independently in duplicate, and extracted study and participant characteristics, exposure and outcome definitions and assessment methods, analysis methods, and adjusted effects and associated uncertainty, all independently in duplicate. Study quality was evaluated by a modified Newcastle-Ottawa score. Random and fixed effects meta-analysis pooled findings, with heterogeneity assessed using the I2 statistic and publication bias by Egger's test and visual inspection of funnel plots. We identified 9 publications including 15 country-specific cohorts, together reporting on 636,151 unique participants with 6.5 million person-years of follow-up and including 28,271 total deaths, 9,783 cases of incident cardiovascular disease, and 23,954 cases of incident diabetes. No RCTs were identified. Butter consumption was weakly associated with all-cause mortality (N = 9 country-specific cohorts; per 14g(1 tablespoon)/day: RR = 1.01, 95%CI = 1.00, 1.03, P = 0.045); was not significantly associated with any cardiovascular disease (N = 4; RR = 1.00, 95%CI = 0.98, 1.02; P = 0.704), coronary heart disease (N = 3; RR = 0.99, 95%CI = 0.96, 1.03; P = 0.537), or stroke (N = 3; RR = 1.01, 95%CI = 0.98, 1.03; P = 0.737), and was inversely associated with incidence of diabetes (N = 11; RR = 0.96, 95%CI = 0.93, 0.99; P = 0.021). We did not identify evidence for heterogeneity nor publication bias. CONCLUSIONS: This systematic review and meta-analysis suggests relatively small or neutral overall associations of butter with mortality, CVD, and diabetes. These findings do not support a need for major emphasis in dietary guidelines on either increasing or decreasing butter consumption, in comparison to other better established dietary priorities; while also highlighting the need for additional investigation of health and metabolic effects of butter and dairy fat. PMID- 27355653 TI - Noninvasive Techniques for the Determination of Burn Severity in Real Time. AB - Visual diagnosis of second-degree burns has proven inadequate for determining the appropriate treatment regimen. Although multiple noninvasive imaging techniques have shown promise for providing information about burn wound severity, the ideal technology to aid burn wound excision would provide real-time readouts. Herein, the authors examine a high-resolution infrared (IR) camera (thermography) and a multiprobe adapter system (MPAS-6; transepidermal evaporative water loss, colorimetry) to assess their usefulness in predicting burn severity. Contact burn wounds of increasing severity were created in a porcine model. Wounds were assessed for 4 days with an IR camera and MPAS-6. In addition, each day, the burn wounds were biopsied for histological analysis to determine burn depth for correlation with noninvasive measures. Surface temperatures decreased with increasing burn severity, which was associated with increasing transepidermal evaporative water loss. Melanin content correlated with the depth of collagen coagulation and was bimodal, with superficial and full-thickness burns having higher values than deep partial thickness wounds. Erythema content was highest in superficial burns and negatively correlated with necrosis (high-mobility group box protein 1 expression). Importantly, surface temperature taken on every single day after injury was predictive of all histologically determined measurements of burn depth (ie, collagen coagulation, apoptosis, necrosis, vascular occlusion). The results indicate that IR imaging and skin quality probes can be used to support the diagnosis of burn severity. Most importantly, IR measurements gave insight into both the zone of coagulation and the zone of stasis on every postburn day studied. PMID- 27355654 TI - Which Burn Outcomes Do Patients Anticipate as Most Likely to Be Important. AB - Burn therapies should focus on achieving outcomes that are most important to patients. The authors wanted to discover which outcomes newly burned patients would anticipate as most important to them and explored the association between demographic/burn characteristics and patient preferences. The authors surveyed 753 of 776 patients seen by our burn service from 2008 to 2013 during the initial encounter. Patients were asked to rate the anticipated importance of several burn outcomes including cosmetic appearance, resumption of normal function, and the lack of pain/itching on a four-item Likert scale (not important, somewhat important, important, and extremely important). The association between demographic and burn characteristics with patient's views on the importance of various outcomes was explored with chi and nonparametric tests. Patient mean (SD) age was 30 (22) years, 58% were males, 69% were white. Overall, function was extremely important to 96% of patients, lack of pain/itching was extremely important to 85% of patients, and cosmesis was extremely important to 59% of patients. Cosmesis was extremely important to more females than males (69 vs 52%; P < .001) and the mean age of patients in whom cosmesis was extremely important was lower than those in whom it was not (25 vs 40; P < .001). Cosmesis was more commonly extremely important in patients with head/neck than extremity burns (67 vs 57%; P < .001). Levels of importance for function and lack of pain/itching did not differ by gender, age, TBSA, or burn location. Thus, return to normal function and lack of pain and itching appear to be more commonly very important to burn patient than the cosmetic appearance of their burns. Cosmesis was of greater importance to younger patients, female patients, and those with head/neck burns. PMID- 27355655 TI - Risk Factors for Ocular Burn Injuries Requiring Surgery. AB - The surgical management of severe ocular burns is challenging and often associated with variable long-term outcome. The aims of this study were to analyze the clinical course of these injuries and determine the factors associated with the need for surgery. A retrospective medical records review was conducted for patients admitted to the Victorian Adult Burns Services, with ocular burns, from January 2000 to January 2010. One hundred and twenty-nine patients were admitted with ocular burns, of which 17 (13.2%) required surgery. The most common indication for surgery was ectropion (n = 9) and the most frequent procedure was full-thickness skin grafts to the eyelids (n = 10). Almost all patients managed surgically developed late ocular complications, the most frequent being visual loss and recurrent ectropion (n = 7 each). Patients undergoing surgery had a longer length of hospital stay (median [interquartile range] 40 [12-90] vs 12 [4-29.5] days; P = .004) and larger TBSA burned (median [interquartile range] 20 [10-60] vs 8 [4-20]; P = .011). Factors associated with the need for surgery included flame burns, periorbital edema, visual loss on presentation, increasing severity of eyelid and facial burns, severe corneal injury, as well as lagophthalmos, ectropion, and microbial keratitis (P < .05). Although only a minority required surgery, these patients often require multiple procedures and develop long-term ocular morbidity. PMID- 27355656 TI - Pediatric Contractures in Burn Injury: A Burn Model System National Database Study. AB - Joint contractures are a major cause of morbidity and functional deficit. The incidence of postburn contractures and their associated risk factors in the pediatric population has not yet been reported. This study examines the incidence and severity of contractures in a large, multicenter, pediatric burn population. Associated risk factors for the development of contractures are determined. Data from the National Institute on Disability and Rehabilitation Research Burn Model System database, for pediatric (younger than 18 years) burn survivors from 1994 to 2003, were analyzed. Demographic and medical data were collected on each subject. The primary outcome measures included the presence of contractures, number of contractures per patient, and severity of contractures at each of nine locations (shoulder, elbow, hip, knee, ankle, wrist, neck, lumbar, and thoracic) at time of hospital discharge. Regression analysis was performed to determine predictors of the presence, severity, and numbers of contractures, with P < .05 used for statistical significance. Of the 1031 study patients, 237 (23%) developed at least 1 contracture at hospital discharge. Among those with at least one contracture, the mean was three (3.3) contractures per person. The shoulder was the most frequently contracted joint (27.9%), followed by the elbow (17.6%), wrist (14.2%), knee (13.3%), and ankle (11.9%). Most contractures were mild (38.5%) or moderate (36.3%) in severity. The statistically significant predictors of contracture development were age and intensive care unit (ICU) length of stay. The statistically significant predictors of severity of contracture were age, ICU length of stay, presence of amputation, and black race. Predictors of the number of contractures included total age, length of stay, length of ICU stay, presence of amputation, TBSA burned, and TBSA grafted. This is the first study to report the epidemiology of postburn contractures in the pediatric population. Approximately one quarter of children with a major burn injury developed a contracture at hospital discharge, and this could potentially increase as the child grows. Contractures develop despite early therapeutic interventions such as positioning and splinting; therefore, it is essential that we identify novel and more effective prevention strategies. PMID- 27355657 TI - Guideline for Burn Care Under Austere Conditions: Special Care Topics. PMID- 27355658 TI - Guidelines for Burn Care Under Austere Conditions: Special Etiologies: Blast, Radiation, and Chemical Injuries. PMID- 27355660 TI - Guidelines for Burn Care Under Austere Conditions: Surgical and Nonsurgical Wound Management. PMID- 27355659 TI - Admission Hyperglycemia Predicts Infectious Complications After Burns. AB - Inflammation and hypermetabolism post burn predisposes to hyperglycemia and insulin resistance. The authors hypothesize that admission hyperglycemia predicts infectious outcomes. A retrospective review of all patients greater than 20 years of age admitted for initial burn management from January 2008 to December 2013 was conducted. Nonthermal injuries, transfers, and those without admission glucose or histories were excluded. Hyperglycemia was defined as admission glucose >=150 mg/dl. Patients were grouped as follows: euglycemic without diabetes (control), euglycemic with diabetes (-H+D), hyperglycemic without diabetes (+H-D), and hyperglycemic with diabetes (+H+D). Outcomes included infection, mortality, length of stay, and disposition. Comparisons were made using Fisher's exact test and multiple logistic regression. A total of 411 patients were analyzed. No significant differences between any of the groups and controls were noted in race, inhalation injury, or obesity. All three groups had higher mortality compared with controls. Longer hospital stays were noted only in +H-D. +H-D and +H+D were less likely to be discharged home than controls. +H-D had higher rates of bacteremia, +H-D and +H+D had higher rates of pneumonia, and H+D and +H-D had higher rates of urinary tract infection. Regression for infection and mortality outcomes with TBSA, age, diabetes, hyperglycemia, obesity, race, gender, and inhalation injury as covariates was performed. Hyperglycemia was the only independent predictor of bacteremia (area under curve [AUC] = 0.736). Hyperglycemia was also a predictor of pneumonia and urinary tract infection (AUC = 0.766 and 0.802, respectively). The only independent predictors of mortality were age, TBSA, and inhalation injury (AUC = 0.892). Acute glucose dysregulation may be more important than diabetes in predicting infectious outcomes after burns. Therefore, admission glucose may have prognostic value. PMID- 27355661 TI - Efficient Synthesis of a Series of Novel Octahydroquinazoline-5-ones via a Simple on-Water Urea-Catalyzed Chemoselective Five-Component Reaction. AB - Multicomponent reactions (MCRs) have become a powerful tool for drug discovery and development owing to their advantages of fast and efficient construction of a large library of products with complexity and diversity. However, conventional MCRs usually proceed in environmentally unfriendly organic solvents rather than in water, a green solvent used by nature for biological chemistry. Herein, a simple and efficient on-water urea-catalyzed chemoselective five-component reaction (5CR) has been developed for the synthesis of a series of novel octahydroquinazoline-5-ones (6), the derivatives of quinazolinones possessing diverse biological activities. The molecular structure of 6{1,1,12} has been confirmed by single-crystal X-ray diffraction. The 5CR can proceed at room temperature under normal atmospheric pressure in good yields and afford a large library of octahydroquinazoline-5-ones with various aromatic and aliphatic substituents at N-1, C-2, and N-3. In addition, a green method has been developed for the synthesis of enaminones, important intermediates in the 5CR and in synthetic chemistry. PMID- 27355662 TI - The bacterial SRP receptor, FtsY, is activated on binding to the translocon. AB - Proteins are inserted into the bacterial plasma membrane cotranslationally after translating ribosomes are targeted to the translocon in the membrane via the signal recognition particle (SRP) pathway. The targeting pathway involves an interaction between SRP and the SRP receptor, FtsY. Here we focus on the role of FtsY and its interaction with the translocon in controlling targeting. We show that in unbound FtsY the NG and A domains interact with one another. The interaction involves the membrane-targeting region at the junction between A and N domain. The closed form of FtsY is impaired in binding to SRP. Upon binding to the phospholipid-embedded translocon the domains of FtsY move apart. This enhances the docking of the FtsY NG domain to the homologous NG domain of the SRP protein Ffh. Thus, FtsY binding to the translocon has a central role in orchestrating the formation of a quaternary transfer complex in which the nascent peptide is transferred to the translocon. We propose that FtsY activation at the translocon ensures that ribosome-SRP complexes are directed to available translocons. This way sequestering SRP in futile complexes with unbound FtsY can be avoided and efficient targeting to the translocon achieved. PMID- 27355663 TI - Development and Validation of a Simple Diagnostic Method to Detect Gain and Loss of Function Defects in Fibroblast Growth Factor-23. AB - BACKGROUND: Fibroblast growth factor-23 (FGF23) is a bone-derived hormone that regulates the homeostasis of phosphate and vitamin D. Three substitutions in the hormone are reported to cause autosomal dominant hypophosphatemic rickets and seven substitutions to cause autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). Both disorders are rare in the general population and occur most often in the Eastern Mediterranean region and Africa. None of the mutations could be identified using standard restriction fragment length polymorphism. The only technique currently available to confirm the clinical diagnosis is DNA sequencing. METHODS: Using a tri-primer ARMS-PCR, in vitro site directed mutagenesis and DNA sequencing, we developed, verified and validated a rapid and reliable diagnostic test for the ten mutations in FGF23. RESULTS: We generated a test for all ten mutations and confirmed each test by DNA sequencing. We increased the specificity of the test by introducing a mismatch at position -2 in the 3'-terminus of the reverse primer of the normal and the mutant sequences. Finally, using DNA sequencing, we validated the technique for FGF23/S129F substitution by testing samples from 80 individuals from two unrelated Arab families harboring HFTC. CONCLUSIONS: This inexpensive and specific method could be adopted where DNA sequencing is not available or affordable. PMID- 27355678 TI - Looking without Perceiving: Impaired Preattentive Perceptual Grouping in Autism Spectrum Disorder. AB - Before becoming aware of a visual scene, our perceptual system has organized and selected elements in our environment to which attention should be allocated. Part of this process involves grouping perceptual features into a global whole. Individuals with autism spectrum disorders (ASD) rely on a more local processing strategy, which may be driven by difficulties perceptually grouping stimuli. We tested this notion using a line discrimination task in which two horizontal lines were superimposed on a background of black and white dots organized so that, on occasion, the dots induced the Ponzo illusion if perceptually grouped together. Results showed that even though neither group was aware of the illusion, the ASD group was significantly less likely than typically developing group to make perceptual judgments influenced by the illusion, revealing difficulties in preattentive grouping of visual stimuli. This may explain why individuals with ASD rely on local processing strategies, and offers new insight into the mechanism driving perceptual grouping in the typically developing human brain. PMID- 27355679 TI - Entomophytophagy ('Sequential Predatory, then Phytophagous Behaviour') in an Indian Braconid 'Parasitoid' Wasp (Hymenoptera): Specialized Larval Morphology, Biology and Description of a New Species. AB - The vast majority of braconid wasps are parasitoids of other insects. Although a few cases of pure phytophagy (primary gall production and seed predation) are known, no previous entomophytophagous species (i.e. ones that display entomophagy and phytophagy sequentially), has been discovered among braconids. We describe the detailed biology and specialized larval morphology for the first confirmed entomophytophagous braconid species. Leaf galls on Garuga pinnata Roxb. (Burseraceae) in India, induced by the psyllid, Phacopteron lentiginosum Buckton (Hemiptera: Psylloidea, Phacopteronidae) were sampled throughout a period of several months and found to suffer a high level of attack by a new species Bracon garugaphagae Ranjith & Quicke which is here described and illustrated. The wasps oviposit singly into the galls without paralysing the psyllids. The larvae first attack psyllid nymphs which they seek out within the gall, kill them with a single bite and consume them. Unique dorsal abdominal tubercles, with eversible tips present on the abdominal segments of the larvae that are used to help maintain larval position while feeding, are illustrated. After consuming all available prey, the larvae continue feeding on gall tissue until mature enough to spin cocoons and pupate. The new species illustrates, for the first time, a possible intermediate stage in the evolution of pure phytophagy within the Braconidae. Interestingly, the two unrelated seed predator Bracon species are also associated with Burseraceae, perhaps indicating that this plant family is particularly suited as a food for braconine wasps. PMID- 27355680 TI - Combined Association of Serum Uric Acid and Metabolic Syndrome with Chronic Kidney Disease in Hypertensive Patients. AB - BACKGROUND/AIMS: Chronic kidney disease (CKD) is one of the major complications of hypertension. It is not only associated with the future burden of end-stage renal disease but also affects mortality and cardiovascular outcomes caused by hypertension. To help understand the pathogenesis and early prevention of progressive CKD, this large-scale study is designed to determine the complex association between serum uric acid (SUA), metabolic syndrome and the prevalence of CKD in hypertensive patients. METHODS: A total of 19,848 hypertensive subjects were enrolled in this cross-sectional study. Patients with proteinuria and/or an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 were considered CKD cases. RESULTS: Hypertensive subjects with CKD had a higher prevalence of hyperuricemia and metabolic syndrome, as well as higher levels of SUA, BMI, waist circumference (WC), SBP, DBP, TG, fasting blood glucose and lower levels of HDL C. Compared to patients without CKD, the multivariate-adjusted odds ratios [ORs, 95% confidence interval (CI)] for CKD patients were 2.30 (2.02-2.63) for hyperuricemia, 1.21 (1.04-1.41) for abdominal obesity, 1.21 (1.06-1.38) for elevated TG, 1.29 (1.06-1.56) for low HDL-C, 1.54 (1.36-1.75) for elevated fasting glucose, and 1.49 (1.30-1.71) for metabolic syndrome. Increasing SUA levels and number of individual metabolic syndrome components were associated with an increased prevalence of CKD. Compared with patients classified in the lowest SUA categories and with <=1 metabolic syndrome components, subjects with HUA and 4 metabolic syndrome components had a 5.77-fold increased OR for CKD based on the multivariate-adjusted analysis. CONCLUSION: Both elevated SUA and metabolic syndrome are associated with an increased prevalence of CKD in hypertensive subjects. Subjects with higher SUA and sum of individual metabolic syndrome components simultaneously have a higher prevalence of CKD. PMID- 27355681 TI - Impact of Visceral Obesity on Microvascular Invasion in Hepatocellular Carcinoma. AB - BACKGROUND: Our objective was to determine whether visceral obesity is associated with increased microvascular invasion (MVI) in patients surgically treated for hepatocellular carcinoma (HCC). METHODS: Data were collected retrospectively in a series of 79 patients treated by surgical resection for HCC, using CT-scan for evaluation of visceral obesity. RESULTS: There was no significant association between visceral obesity and MVI (OR = 1.20 (0.38-3.75), p = 0.75). Independent predictive factors of MVI were moderate/poor differentiation, tumor size above 50 mm and underlying cirrhosis. CONCLUSION: This study did not support the hypothesis that visceral obesity might promote MVI in patients with HCC. PMID- 27355682 TI - Association of Low-Birth Weight with Malnutrition in Children under Five Years in Bangladesh: Do Mother's Education, Socio-Economic Status, and Birth Interval Matter? AB - BACKGROUND: Malnutrition in children under five years remains a significant problem in Bangladesh, despite substantial socio-economic progress and a decade of interventions aimed at improving it. Although several studies have been conducted to identify the important risk factors of malnutrition, none of them assess the role of low birth weight (LBW) despite its high prevalence (36%). This study examines the association between LBW and malnutrition using data from the Bangladesh Demographic and Health Survey (BDHS) 2011 and provides practical guidelines for improving nutritional status of children. METHODS: Malnutrition in children is measured in terms of their height-for-age, weight-for-height, and weight-for-age. Children whose Z-scores for either of these indices are below two standard deviations (-2SD) from median of WHO's reference population are considered as stunted, wasted or underweight, respectively. The association between malnutrition and LBW was investigated by calculating adjusted risk-ratio (RR), which controls for potential confounders such as child's age and sex, mother's education and height, length of preceding-birth-interval, access to food, area of residence, household socio-economic status. Adjusted RR was calculated using both Cochran-Mantel-Haenszel approach and multivariable logistic regression models controlling for confounder. RESULTS: The prevalence of malnutrition was markedly higher in children with LBW than those with normal birth-weights (stunting: 51% vs 39%; wasting: 25% vs 14% and underweight: 52% vs 33%). While controlling for the known risk factors, children with LBW had significantly increased risk of becoming malnourished compared to their counter part with RR 1.23 (95% CI:1.16-1.30), 1.71 (95% CI:1.53-1.92) and 1.47 (95% CI: 1.38-1.56) for stunting, wasting and underweight, respectively. The observed associations were not modified by factors known to reduce the prevalence of malnutrition, such as higher education of mother, better household socio-economic conditions and longer birth-interval. CONCLUSIONS: Higher education of mother, better household socio-economic conditions and prolonged birth intervals alone are not sufficient in bringing about substantial reductions in prevalence of child malnutrition in Bangladesh. Targeted interventions should be designed to reduce prevalence of LBW in addition to improving mother's education and other socio-demographic conditions. PMID- 27355683 TI - The Development of White-Asian Categorization: Contributions from Skin Color and Other Physiognomic Cues. AB - We examined the development of racial categorizations of faces spanning the European-East Asian ("White-Asian") categorical continuum in children between the ages of four and nine as well as adults. We employed a stimulus set that independently varied skin color and other aspects of facial physiognomy, allowing the contribution of each to be assessed independently and in interaction with each other. Results demonstrated substantial development across this age range in children's ability to draw on both sorts of cue, with over twice as much variance explained by stimulus variation in adults than children. Nonetheless, children were clearly sensitive to both skin color and other aspects of facial physiognomy, suggesting that understanding of the White-Asian category boundary develops in a somewhat different way than understanding of the White-Black category boundary, in which attention to features other than skin color appear only somewhat later. Discussion focuses on the implications of these findings for theories of social categorization. PMID- 27355684 TI - The impact of patient protection and Affordable Care Act on trauma care: A step in the right direction. AB - INTRODUCTION: The Patient Protection and Affordable Care Act (ACA) was implemented to guarantee financial coverage for health care for all Americans. The implementation of ACA is likely to influence the insurance status of Americans and reimbursement rates of trauma centers. The aim of this study was to assess the impact of ACA on the patient insurance status, hospital reimbursements, and clinical outcomes at a Level I trauma center. We hypothesized that there would be a significant decrease in the proportion of uninsured trauma patients visiting our Level I trauma center following the ACA, and this is associated with improved reimbursement. METHODS: We performed a retrospective analysis of the trauma registry and financial database at our Level I trauma center for a 27-month (July 2012 to September 2014) period by quarters. Our outcome measures were change in insurance status, hospital reimbursement rates (total payments/expected payments), and clinical outcomes before and after ACA (March 31, 2014). Trend analysis was performed to assess trends in outcomes over each quarter (3 months). RESULTS: A total of 9,892 patients were included in the study. The overall uninsured rate during the study period was 20.3%. Post-ACA period was associated with significantly lower uninsured rate (p < 0.001). During the same time, there was as a significant increase in the Medicaid patients (p = 0.009). This was associated with significantly improved hospital reimbursements (p < 0.001).On assessing clinical outcomes, there was no change in hospitalization (p = 0.07), operating room procedures (p = 0.99), mortality (p = 0.88), or complications (p = 0.20). Post-ACA period was also not associated with any change in the hospital (p = 0.28) or length of stay at intensive care unit (p = 0.66). CONCLUSION: The implementation of ACA has led to a decrease in the number of uninsured trauma patients. There was a significant increase in Medicaid trauma patients. This was associated with an increase in hospital reimbursements that substantially improved the financial revenues. Despite the controversies, implementation of ACA has the potential to substantially improve the financial outcomes of trauma centers through Medicaid expansion. LEVEL OF EVIDENCE: Economic and value-based evaluation, level III. PMID- 27355686 TI - If you're not at the table, you're on the menu. PMID- 27355685 TI - Apical Secretion of FSTL1 in the Respiratory Epithelium for Normal Lung Development. AB - Follistatin-like 1 (FSTL1) is a secreted bone morphogenetic protein (BMP) antagonist, and it plays a crucial role in normal lung development. Deletion of Fstl1 leads to postnatal death in mice due to respiratory failure. To further explore the role of FSTL1 in mouse lung development, we created a transgene SFTPC Fstl1 allele mouse displaying significant epithelial overexpression of Fstl1 in all stages of lung development. However, epithelial overexpression of Fstl1 did not alter lung morphogenesis, epithelial differentiation and lung function. Moreover, we found that FSTL1 function was blocked by the epithelial polarization, which was reflected by the remarkable apical secretion of FSTL1 and the basolateral BMP signaling. Taken together, this study demonstrates that tightly spatial interaction of FSTL1 and BMP signaling plays an essential role in lung development. PMID- 27355687 TI - Understanding acute pancreatitis. PMID- 27355689 TI - Reductive Coupling of Diynes at Rhodium Gives Fluorescent Rhodacyclopentadienes or Phosphorescent Rhodium 2,2'-Biphenyl Complexes. AB - Reactions of [Rh(kappa(2) -O,O-acac)(PMe3 )2 ] (acac=acetylacetonato) and alpha,omega-bis(arylbutadiynyl)alkanes afford two isomeric types of MC4 metallacycles with very different photophysical properties. As a result of a [2+2] reductive coupling at Rh, 2,5-bis(arylethynyl)rhodacyclopentadienes (A) are formed, which display intense fluorescence (Phi=0.07-0.54, tau=0.2-2.5 ns) despite the presence of the heavy metal atom. Rhodium biphenyl complexes (B), which show exceptionally long-lived (hundreds of MUs) phosphorescence (Phi=0.01 0.33) at room temperature in solution, have been isolated as a second isomer originating from an unusual [4+2] cycloaddition reaction and a subsequent beta-H shift. We attribute the different photophysical properties of isomers A and B to a higher excited state density and a less stabilized T1 state in the biphenyl complexes B, allowing for more efficient intersystem crossing S1 ->Tn and T1 ->S0 . Control of the isomer distribution is achieved by modification of the bis- (diyne) linker length, providing a fundamentally new route to access photoactive metal biphenyl compounds. PMID- 27355690 TI - Roses Are Red, Socks Are Blue: Switching Dimensions Disrupts Young Children's Language Comprehension. AB - Language is used to identify objects in many different ways. An apple can be identified using its name, color, and other attributes. Skilled language comprehension requires listeners to flexibly shift between different dimensions. We asked whether this shifting would be difficult for 3-year-olds, who have relatively immature executive function skills and struggle to switch between dimensions in card sorting tasks. In the current experiment, children first heard a series of sentences identifying objects using a single dimension (either names or colors). In the second half of the experiment, the labeling dimension was switched. Children were significantly less accurate in fixating the correct object following the dimensional switch. This disruption, however, was temporary; recognition accuracy recovered with increased exposure to the new labeling dimension. These findings provide the first evidence that children's difficulty in shifting between dimensions impacts their ability to comprehend speech. This limitation may affect children's ability to form rich, multi-dimensional representations when learning new words. PMID- 27355692 TI - A Standardized Composition from Extracts of Myristica Fragrans, Astragalus Membranaceus, and Poria Cocos Protects Liver from Acute Ethanol Insult. AB - Despite the promising advances in therapeutic discovery, there still is a major challenge in the development of a safe, effective, and economical intervention for managing alcohol-related liver disorders. In this study, we describe the potential use of "MAP," a standardized composition comprising three extracts from Myristica fragrans, Astragalus membranaceus, and Poria cocos, in ameliorating alcohol-induced acute liver toxicity. Ethanol-induced acute hepatotoxicity as an animal model of binge drinking was utilized. Mice received oral doses of MAP at 300 mg/kg for four consecutive days. Mice were orally gavaged with 50% ethanol in 12 mL/kg dosing volume following the third dose of MAP every 12 h thereafter for a total of three doses. Hepatic functional tests from serum collected at T12, and hepatic glutathione (GSH), superoxide dismutases (SODs), and triglyceride from liver homogenates were evaluated. Histopathology analysis and alcoholic steatohepatitis (ASH) scoring were also determined. Excessive increases of serum alanine aminotransferase and aspartate aminotransferase were significantly inhibited at 46.3% and 43.6%, respectively, when mice were treated with MAP. MAP replenished the depleted SOD by more than 60%, while causing significant stimulation of GSH productions. MAP showed statistically significant reduction in ballooning degeneration, vascular steatosis, cytoplasmic or nuclear condensation, and shrinkage, as well as inflammations when compared to vehicle-treated alcohol induced liver toxicity model. Mice treated with MAP showed statistically significant reduction in ASH scoring when compared to vehicle control. Therefore, the composition MAP could be potentially utilized as an effective hepatic detoxifying agent for the protection of liver damage caused by alcohol consumptions. PMID- 27355693 TI - Ten Emerging Trends in the Epidemiology of Diabetic Retinopathy. AB - PURPOSE: Diabetes is a major public health problem affecting 415 million people worldwide. With the increasing prevalence of diabetes, diabetic retinopathy (DR) is emerging as the leading cause of avoidable blindness worldwide. METHODS: We reviewed previous and recent literature to provide an overview of emerging trends on the burden, epidemiology, risk factors, and prevention of DR. RESULTS: First, there is clear evidence of a global increase in the prevalence of diabetes. Second, there is a decline in the incidence of blindness due to DR, particularly in developed countries. Third, diabetic macular edema (DME) rather than proliferative diabetic retinopathy (PDR) is the increasingly common cause of visual impairment. Fourth, DR awareness remains patchy and low in most populations. Fifth, hyperglycemia remains the most consistent risk factor for DR in type 1 diabetes across different studies and populations. Sixth, in contrast, blood pressure is an important risk factor for DR in type 2 diabetes. Seventh, the relationship between dyslipidemia and DR remains unclear, with inconsistent results from different studies and trials. Eighth, the utility of predictive models incorporating multiple risk factors for assessing DR risk requires evaluation. Ninth, photographic screening of DR using tele-ophthalmology platforms is increasingly recognized as being feasible and cost-effective. Finally, DR prevention in low-resource settings cannot follow models developed in high-resource countries and requires different strategies. CONCLUSIONS: The ten trends we observed in the current review may guide planning of public healthcare strategies for the management of DR and prevention of blindness. PMID- 27355694 TI - Testing the Habituation-Based Model of Exposures for Child and Adolescent Anxiety. AB - Exposure has been identified as key to effective treatment of youth anxiety. However, the precise theoretical mechanisms of exposure are a matter of debate. Emotional processing theory emphasizes the need for fear activation during exposure and its habituation both within and across exposures. Despite the popularity of the theory to explain exposure, it has not been tested with anxious youth. To determine whether emotional processing theory parameters predict anxiety severity, coping abilities, and global functioning after cognitive behavioral treatment. The present study examined 72 youth (Mage = 10.50 years; 45% female; 87.5% non-Hispanic Caucasian) diagnosed with an anxiety disorder and who received family or individual CBT. Three exposure habituation variables initial fear activation (peak anxiety), within-session habituation, and between session habituation-were assessed using Subjective Units of Distress and examined as predictors of outcome at posttreatment and at 1-year follow-up. Outcomes were measured using the Coping Questionnaire, Multidimensional Anxiety Scale for Children, Revised Children's Manifest Anxiety Scale, Children's Global Assessment Scale, and clinician severity ratings on the Anxiety Disorder Interview Schedule. Emotional processing theory variables did not predict any anxiety outcomes at posttreatment or follow-up with one exception: Initial fear activation predicted less anxiety at follow-up among youth without GAD. In addition, within- and between-session habituation were not associated with one another. Between-session habituation was not associated with initial fear activation. These findings suggest a limited role of habituation within cognitive-behavioral therapy for anxiety in youth. An alternative to emotional processing theory, inhibitory learning theory, is discussed. PMID- 27355695 TI - High-Pressure Synthesis of Manganese Oxyhydride with Partial Anion Order. AB - The high-pressure synthesis of a manganese oxyhydride LaSrMnO3.3 H0.7 is reported. Neutron and X-ray Rietveld analyses showed that this compound adopts the K2 NiF4 structure with hydride ions positioned exclusively at the equatorial site. This result makes a striking contrast to topochemical reductions of LaSrMnO4 that result in only oxygen-deficient phases down to LaSrMnO3.5 . This suggests that high H2 pressure plays a key role in stabilizing the oxyhydride phase, offering an opportunity to synthesize other transition-metal oxyhydrides. Magnetic susceptibility revealed a spin-glass transition at 24 K that is due to competing ferromagnetic (Mn(2+) -Mn(3+) ) and antiferromagnetic (Mn(2+) -Mn(2) , Mn(3+) -Mn(3+) ) interactions. PMID- 27355696 TI - Autochthonous self-assembly of nature's nanomaterials: green, parsimonious and antibacterial carbon nanofilms on glass. AB - The development of thin film coatings has been a very important development in materials science for the modification of native material surface properties. Thin film coatings are enabled through the use of sophisticated instruments and technologies that demand expertise and huge initial and running costs. Nano-thin films are yet a furtherance of thin films which require more expertise and much more sophistication. In this work for the first time we present a one-pot straightforward carbon thin film coating methodology for glass substrates. There is novelty in every single aspect of the method, with the carbon used in the nanofilm being obtained from turmeric soot, the coating technique consisting of a basic immersion technique, a dip-dry method, in combination with the phytosoot derived carbon's inherent ability to self-assemble to form a uniform and continuous stable coating. The carbon nanofilm has been characterized using field emission scanning electron microscopy (FESEM), Energy Dispersive X-ray (EDAX) analysis, a goniometer and X-ray diffraction (XRD). This study for the first time opens a new school of thought of using such naturally available free nanomaterials as eco-friendly green coatings. The amorphous porous carbon film can be coated on any hydrophilic substrate and is not substrate specific. Its added advantages of being transparent and antibacterial in spite of being green and parsimonious are meant to realize its utility as ideal choices for solar panels, medical implants and other construction applications. PMID- 27355697 TI - Fused Dibenzo[a,m]rubicene: A New Bowl-Shaped Subunit of C70 Containing Two Pentagons. AB - Total synthetic approaches of fullerenes are the holy grail for organic chemistry. So far, the main attempts have focused on the synthesis of the buckminsterfullerene C60. In contrast, access to subunits of the homologue C70 remains challenging. Here, we demonstrate an efficient bottom-up strategy toward a novel bowl-shaped polycyclic aromatic hydrocarbons (PAH) C34 with two pentagons. This PAH represents a subunit for C70 and of other higher fullerenes. The bowl-shaped structure was unambiguously determined by X-ray crystallography. A bowl-to-bowl inversion for a C70 fragment in solution was investigated by dynamic NMR analysis, showing a bowl-to-bowl inversion energy (DeltaG(?)) of 16.7 kcal mol(-1), which is further corroborated by DFT calculations. PMID- 27355698 TI - The Lived Experiences of People With Chronic Obstructive Pulmonary Disease: A Phenomenological Study. AB - PURPOSE: This study explored the lived experiences of people with chronic obstructive pulmonary disease (COPD) following hospitalization for acute exacerbation or pneumonia. DESIGN AND METHOD: A phenomenological approach was adopted to collect data through semistructured interviews. Fourteen participants were recruited from a medical center in northern Taiwan. Data were collected from January 2013 to January 2014. Giorgi's phenomenological methodology was adopted to analyze the interview content. FINDINGS: Three phenomenological themes emerged: trapped in an invisible cage, torments in the winter, and striving for wellness. CONCLUSIONS: This study sought to elucidate the lived experiences of people with COPD, who perceived themselves as feeling an overwhelming sense of confinement. The interviewees displayed positive attitudes, indicating that people with COPD are willing to cope with their disease. Health practitioners should focus on educating people with COPD about their needs, encouraging them to be more positive, and assisting them in engaging in self-management. CLINICAL RELEVANCE: People with COPD can cope with the disease and seek alternative methods to improve their health. These positive attitudes could be used to encourage self-management in the future. PMID- 27355741 TI - Unveil the Chemistry of Olivine FePO4 as Magnesium Battery Cathode. AB - Despite growing interest in magnesium batteries, it is still a challenge to find a cathode that fulfills requirements such as high capacity and good cyclability. Because of their positions in the periodic table and the similar ionic sizes of lithium and magnesium, it was naturally postulated that a classical intercalation type Li-ion battery cathode may also accommodate the intercalation of Mg. On the contrary, many Li-ion battery cathodes performed very poorly in Mg cells, although the mechanism behind such phenomena is still unclear. Here we provide first-hand evidence about the chemistry of olivine FePO4 as Mg battery cathode using a combined theoretical and experimental approach. Although LiFePO4 is a commercial cathode with extraordinary good performance in Li-ion batteries, the measured capacity of FePO4 in nonaqueous Mg cell was only ~13 mAh/g. Density functional theory calculations predicted sufficient mobility of Mg(2+) in FePO4 lattice to support the insertion of Mg at a reasonable rate, suggesting the poor performance cannot be simply attributed to the limitation of Mg(2+) diffusion. Instead, the recorded low capacity was the result of surface amorphorization that prohibited the electrochemical reaction from penetrating deeply into the bulk phase. The amorphorization had a thermodynamic origin from the instability of intercalated product, which was predicted from DFT calculations and supported by the failure to synthesize magnesiated FePO4 in the solid state reaction route. These results highlighted the importance of a thermodynamically preferred intercalation in order to achieve successful Mg battery cathode. PMID- 27355699 TI - Atomic Resolution Structure of Monomorphic Abeta42 Amyloid Fibrils. AB - Amyloid-beta (Abeta) is a 39-42 residue protein produced by the cleavage of the amyloid precursor protein (APP), which subsequently aggregates to form cross-beta amyloid fibrils that are a hallmark of Alzheimer's disease (AD). The most prominent forms of Abeta are Abeta1-40 and Abeta1-42, which differ by two amino acids (I and A) at the C-terminus. However, Abeta42 is more neurotoxic and essential to the etiology of AD. Here, we present an atomic resolution structure of a monomorphic form of AbetaM01-42 amyloid fibrils derived from over 500 (13)C (13)C, (13)C-(15)N distance and backbone angle structural constraints obtained from high field magic angle spinning NMR spectra. The structure (PDB ID: 5KK3 ) shows that the fibril core consists of a dimer of Abeta42 molecules, each containing four beta-strands in a S-shaped amyloid fold, and arranged in a manner that generates two hydrophobic cores that are capped at the end of the chain by a salt bridge. The outer surface of the monomers presents hydrophilic side chains to the solvent. The interface between the monomers of the dimer shows clear contacts between M35 of one molecule and L17 and Q15 of the second. Intermolecular (13)C-(15)N constraints demonstrate that the amyloid fibrils are parallel in register. The RMSD of the backbone structure (Q15-A42) is 0.71 +/- 0.12 A and of all heavy atoms is 1.07 +/- 0.08 A. The structure provides a point of departure for the design of drugs that bind to the fibril surface and therefore interfere with secondary nucleation and for other therapeutic approaches to mitigate Abeta42 aggregation. PMID- 27355742 TI - Bone healing after biodegradable mini-plate fixation. AB - PURPOSE: To compare bone healing in mandibular vertical body osteotomies (MVBO) after fixation with a resorbable 2.0mm-profile fixation system in the first and third postoperative months in rabbits. METHODS: Twenty hemimandibles of ten rabbits were divided into two groups according to duration of resorbable fixation one or three months. The MVBOs were performed and one four-hole, resorbable, 2.0mm mini-plate fixation system was used on each side. The computed tomography (CT) scans, scanning electron microscopy (SEM), and histomorphometric outcomes of groups I and II were compared. RESULTS: Significant differences were found between the one- and three- month assessments in terms of newly formed bone ratio values (p<0.05). There was more new bone formation at the third month on both the CT and histomorphometric examinations. A better adaptation of the bone tissues to the resorbable mini-plate and screws was observed on SEM at three months. CONCLUSION: The resorbable mini-plates provided a fixation stable enough to allow immediate oral alimentation and callus formation in both groups. PMID- 27355743 TI - Treatment of abdominal wall hernia with suture, or polypropylene, or collagen prosthesis. AB - PURPOSE: To develop an experimental model for incisional hernias and to compare morphological and functional aspects of hernia repairs by suture, polypropylene mesh and collagen mesh. METHODS: A defect measuring 7cm x 2cm was created in the anterior abdominal of 28 New Zealand male rabbits, divided into four groups (n = 7): (1) control, (2) suture of the anterior sheath of the rectus abdominal muscle, (3) setting of polypropylene mesh, and (4) setting of collagen mesh. On the 90th postoperative day, the animals were examined to verify the presence of incisional hernia. Samples of abdominal wall and scar were collected for histological study. RESULTS: Incisional hernia was identified in 85.7% of the control group, 57.1% of the suture group, 42.9% of the collagen mesh group, and none in the polypropylene mesh group (p = 0.015). Mesh exposure could be identified in 71.4% of the animals in group 3 and in no animal in group 4 (p = 0.021). The polypropylene mesh is effective in the treatment of abdominal wall defects, causing an intense inflammatory reaction. CONCLUSION: The collagen mesh is biocompatible, producing a minimal inflammatory reaction, but fails in the treatment of abdominal wall defects. PMID- 27355744 TI - Treatment of fistula-in-ano with cyanoacrylate glue with and without prior seton placement in rats. AB - PURPOSE: To evaluate the efficacy of ethyl-cyanoacrylate in the treatment of fistula-in-ano in rats with and without prior seton placement. METHODS: Thirty rats Wistar with fistula-in-ano produced surgically, distributed in three groups: group A (ethyl-cyanoacrylate) - treated by application of ethyl-cyanoacrylate into fistula tract; group B (seton + ethyl-cyanoacrylate) - seton placement followed by application of ethyl-cyanoacrylate into fistula tract, 30 days later; group C (control) - no treatment. After 60 days the animals were submited to euthanasia and the specimens were analyzed by pathologist. The results were analyzed by Chi-square test with significant value of p<0.05. RESULTS: One animal of group B died. Were found tracts fully healed: 7, 5 and 2, in groups A, B and C, respectivelly. There was a statistically significant difference between groups A and C (p=0.02). When joined all animals treated with glue (A + B) compared to group C there was also statistically significant difference (p=0.02). CONCLUSIONS: The use of ethyl-cyanoacrylate glue was effective in closing anal fistulae in rats. There was no advantage in the prior application of seton. PMID- 27355745 TI - Neutrophil elastase ameliorates matrix metalloproteinase-9 to promote lipopolysaccharide-induced acute lung injury in mice 1. AB - PURPOSE: To investigate the regulatory roles of neutrophil elastase (NE) and matrix metalloproteinase-9 (MMP-9) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. METHODS: To construct LPS-induced ALI mouse models, wild type C57BL/6 mice were administered 5.0 mg/kg of LPS through endotracheal, and/or 1.0 mg/kg of ONO-5046, and/or 20.0 mg/kg of chemically modified tetracycline-3 (CMT-3) by gavage. The levels of MMP-9, tissue inhibitor of metalloprotease-1, interleukin (IL)-6 were detected by real time RT-PCR at 6 h, 24 h and 48 h, and tumor necrosis factor (TNF), lung wet-dry weight ratio, white blood cell (WBC) count and polymorphonuclear (PMN) count in bronchoalveolar lavage fluid (BALF) were tested at 48 h after administration. The 5-day survival analysis of the ALI mice was also performed. RESULTS: Both ONO-5046 and CMT-3, regardless of being used individually or combined, significantly reduced the levels of MMP-9, IL-6, and TNF in lung tissue as well as in BALF, and the WBC and PMN count in BALF. Combined treatment with ONO-5046 and CMT-3 remarkably improved the survival rate of ALI mice. CONCLUSION: Neutrophil elastase synergizes with matrix metalloproteinase-9 to promote and regulate the release of inflammatory mediators and the infiltration of inflammatory cells, consequently affecting the survival of lipopolysaccharide-induced acute lung injury mice. PMID- 27355746 TI - The potential efficacy of Survanta (r) and Seprafilm (r) on preventing intra abdominal adhesions in rats. AB - PURPOSE: To investigate the potential efficacy of beractant (Survanta(r)) and Seprafilm(r) on the prevention of postoperative adhesions. METHODS: Forty Wistar albino female rats were used. The rats were randomly allocated into four groups of 10 rats each as control group (CG), beractant group (BG), Seprafilm(r) group (SG), and combined group (COG). All rats underwent cecal abrasion via midline laparotomy. Before abdominal closure, isotonic saline, beractant, Seprafilm, and combined agents were intraperitoneally administered. Adhesions were classified macroscopically with Canbaz Scoring System on postoperative day 10. Ceacum was resected for histopathological assessment. RESULTS: Macroscopic adhesion scores were significantly lower in BG, SG, and COG than CG (p<0.05); (45%, 15%, 25%, and 15%; respectively). Histopathological assessment revealed a reduced inflammation and fibrosis score in the study groups than CG (p<0.05). In BG, adhesion development, inflammation and fibrosis scores were lower than SG; however, it was not statistically significant. CONCLUSIONS: Intra-abdominal application of beractant is significantly effective for the prevention of adhesion formation with no adverse effect by covering the whole peritoneal mesothelium with excellent gliding properties in a rat model. The combination of both agents is also effective in reducing adhesion formation, however, not superior to single beractant application. PMID- 27355747 TI - Therapeutic effects of ellagic acid on L-arginin induced acute pancreatitis. AB - PURPOSE: To investigate the therapeutic effects of ellagic acid on L-arginin induced acute pancreatitis in rats. METHODS: Thirty-two were split into four groups. Group 1 (control) rats were performed only laparotomy, no drugs were administered. Group 2 (control+EA) rats were administered 85mg/kg EA orally. Rats were sacrificed by cardiac puncture 24 hours after the administration. Group3 (AP) 24 hours after intraperitoneal L-arginine administration, rats were sacrificed by cardiac puncture. Group 4 (EA)-(AP): 85mg/kg EA was administered orally after the L-arginine administration. 24 hours later, rats were sacrificed by cardiac puncture. Serum TNF-alpha, IL-1beta, IL-6, total oxidative status (TOS), total antioxidant capacity (TAC), amylase levels were determined in all groups. RESULTS: Group 3 (AP) rats showed significantly raised TOS level as compared to Group1 (control) rats (p<0.001). Following the EA therapy, a decrease in TOS was observed in Group 4 (AP+EA). TAC levels were significantly raised in the Group 4 (AP+EA) compared to the Group 3 (AP) (p=0.003). Group 3 (AP) showed significantly increased TNF-alpha, IL-1beta and IL-6 serum levels as compared to Group 4 (AP+EA). Histopathological changes were supported our result. CONCLUSION: The healing effects of ellagic acid on inflammatory and oxidative stress were confirmed by histopathological and biochemical evaluations of the pancreatic tissue. PMID- 27355748 TI - Schinus terebinthifolius raddi (Aroeira) and Orbignya phalerata mart. (Babassu) effect in cecorrahphy healing in rats. AB - PURPOSE: To evaluate the effect of Schinus terebinthifolius Raddi (aroeira) and Orbignya phalerata Mart. (babassu) in the healing process of cecorrhaphy in rats. METHODS: : Fifty four rats were used, distributed into three groups randomly: aroeira, babassu and control, which were divided into three subgroups (six animals) according to the time of the deaths (7, 14, 21 days). All underwent the same surgical procedure, cecotomy and cecorrhaphy. The animals in group aroeira and babassu received daily dose of 100 mg/kg of hydroalcoholic extract and 50 mg/kg of aquous extract respectively, by gavage. The control group received only saline solution. The parameters evaluated were: macroscopic changes, ,resistance test to air insufflations and histological changes. RESULTS: : All animals showed good healing without infection. All groups presented adhesions between cecum and neighboring organs. The resistance test insufflating of atmospheric air showed progressive increase of pressure according to the days in the aroeira group, and decrease in babassu group, without significant difference. Microscopy showed significant difference in the polymorphonuclear, hyperemia, angiogenesis, fibroblast proliferation and collagen histological variables in the 14th day. CONCLUSION: : Hydroalcoholic extract of aroeira and the aqueous extract of babassu favored the healing process in cecorrhaphy in rats. PMID- 27355749 TI - Protective effect of metformin on testicular ischemia/reperfusion injury in rats. AB - PURPOSE: To investigate the protective effect of metformin on testicular ischemia/reperfusion (I/R) injury in rats. METHODS: Eighteen adult male Wistar rats were randomly divided into three experimental groups (n=6), as follows: Sham, I/R, and Metformin. 1-hour ischemia was induced by the left testicular artery and vein clipping followed by 7 days of reperfusion. Metformin (100 mg/kg) was administrated orally for 7 days via oral gavage after ischemic period. At the end of trial, the left testis was removed for histological analysis and oxidative stress measurement. RESULTS: I/R reduced superoxide dismutase (SOD) activities and testicular Johnsen's scores accompanied by an elevation in malondialdehyde (MDA) and myeloperoxidase (MPO) levels in comparison with the sham group (P < 0.05). Compared to I/R group, metformin restored testicular Johnsen's scores, SOD activity, MDA and MPO levels (P < 0.05). CONCLUSION: Metformin has a protective effect against I/R injury on the testis. PMID- 27355750 TI - Effect of Otostegia persica extract on ischemia/reperfusion induced renal damage in diabetic rats. A biochemical study. AB - PURPOSE: To evaluate the effect of Otostegia persica (O. persica) extract on renal damage induced by ischemia/reperfusion (I/R) in diabetic rats. METHODS: Forty-eight rats were subjected to right nephrectomy; then, they were allocated into six groups: Sham; Diabetic sham; I/R; Diabetic I/R; I/R+O. persica; Diabetic I/R+O. persica. Diabetes was induced by streptozotocin (200 mg/kg, i.p.). O. persica (300 mg/kg/day, p.o) was administered for 2 weeks. On the 15th day, ischemia was induced in left kidney for 60 min, followed by reperfusion for 24h. Renal functional and biochemical markers were estimated. RESULTS: I/R in both normal and diabetic rats, induced a significant elevation in serum levels of urea and creatinine (p<0.05). Renal I/R induced a significant increase of malondialdehyde, myeloperoxidase and nitric oxide concentrations associated with significant reduction in superoxide dismutase and catalase activities in comparison with the sham group (p<0.05). Diabetic rats that underwent renal I/R exhibited a significant increase in all the studied parameters with a reduction in the antioxidant enzymes as compared to nondiabetic rats (p<0.05). These deleterious effects associated with renal I/R were improved by the treatment with O. persica (p<0.05). CONCLUSION: Otostegia persica pretreatment protected the renal injury from ischemia-reperfusion in diabetic rats. PMID- 27355751 TI - The use of a biocompatible cement in endodontic surgery. A randomized clinical trial 1. AB - PURPOSE: To evaluate the clinical applicability of Pozzolana Biologic Silva cement (PBS(r)) in endodontic surgery. METHODS: Persistent apical periodontitis was diagnosed in 30 teeth of 12 patients by cone-beam computed tomography (CT). All patients had 2 or 4 affected teeth and underwent endodontic surgery with root end filling. Patients with 2 affected teeth had one tooth (control) treated with mineral trioxide aggregate (MTA-Angelus(r)) as a root-end filling material, and the other tooth treated with PBS (experiment). When the patient had four affected teeth, two of them were treated with MTA and two with PBS. Six months after surgery, all patients were assessed by CT scan. Between-group comparisons of measurements were performed using the Wilcoxon test. RESULTS: Periradicular tissue regeneration was observed in all cases. Significant within-group differences in long axes of the lesion were found in the bucco-palatal direction (PBS group, p=0.0012; MTA group, p=0.024) and coronal-apical direction (PBS group, p=0.0007; MTA group, p=0.0015) between pre- and postoperative measurements. CONCLUSIONS: Pozzolana Biologic Silva cement can be used in the treatment of persistent periradicular lesions. The clinical use of PBS as a root end filling material may be an alternative to MTA. PBS has additives, which provide enhanced strength. PMID- 27355752 TI - Three-Dimensional Reduced Graphene Oxide Coupled with Mn3O4 for Highly Efficient Removal of Sb(III) and Sb(V) from Water. AB - Highly porous, three-dimensional (3D) nanostructured composite adsorbents of reduced graphene oxides/Mn3O4 (RGO/Mn3O4) were fabricated by a facile method of a combination of reflux condensation and solvothermal reactions and systemically characterized. The as-prepared RGO/Mn3O4 possesses a mesoporous 3D structure, in which Mn3O4 nanoparticles are uniformly deposited on the surface of the reduced graphene oxide. The adsorption properties of RGO/Mn3O4 to antimonite (Sb(III)) and antimonate (Sb(V)) were investigated using batch experiments of adsorption isotherms and kinetics. Experimental results show that the RGO/Mn3O4 composite has fast liquid transport and superior adsorption capacity toward antimony (Sb) species in comparison to six recent adsorbents reported in the literature and summarized in a table in this paper. Theoretical maximum adsorption capacities of RGO/Mn3O4 toward Sb(III) and Sb(V) are 151.84 and 105.50 mg/g, respectively, modeled by Langmuir isotherms. The application of RGO/Mn3O4 was demonstrated by using drinking water spiked with Sb (320 MUg/L). Fixed-bed column adsorption experiments indicate that the effective breakthrough volumes were 859 and 633 mL bed volumes (BVs) for the Sb(III) and Sb(V), respectively, until the maximum contaminant level of 5 ppb was reached, which is below the maximum limits allowed in drinking water according to the most stringent regulations. The advantages of being nontoxic, highly stable, and resistant to acid and alkali and having high adsorption capacity toward Sb(III) and Sb(V) confirm the great potential application of RGO/Mn3O4 in Sb-spiked water treatment. PMID- 27355753 TI - Case report of diet-related improvements of non-alcoholic steatohepatitis evaluated by four consecutive liver biopsies. AB - We report the case of a 46-year-old man who achieved remarkable improvement of characteristic non-alcoholic steatohepatitis by dieting. Initially, his body mass index was 40.7 kg/m2 . He proactively commenced a low calorie diet and his body mass index decreased to 28 kg/m2 after 4 years. During the same period, we carried out liver biopsy four times. Liver fibrosis as well as inflammation, steatosis and ballooning improved, and the non-alcoholic fatty liver disease activity score decreased from 4 to 0. The fat deposits of liver tissue changed from macrovesicular droplets to microvesicular, and finally disappeared. Along with improved histology, alanine aminotransferase, homeostasis model assessment insulin resistance, ferritin, leptin, high-sensitivity C-reactive protein and cytokeratin 18 decreased, and adiponectin increased linearly. However, no clear changes were observed in markers for Wisteria floribunda agglutinin-positive Mac 2 binding protein (WFA+ M2BP), type IV collagen 7S, procollage III peptide and fibrosis-4 index along with dieting. This is the first study to report gradual improvement of liver histology during four liver biopsies and fibrosis markers in a patient with non-alcoholic steatohepatitis who achieved complete recovery solely by dieting. PMID- 27355754 TI - Photocatalytic Anion Oxidation and Applications in Organic Synthesis. AB - Ions and radicals of the same kind differ by one electron only. The oxidation of many stable inorganic anions yields their corresponding highly reactive radicals, and visible light excitable photocatalysts can provide the required oxidation potential for this transformation. Air oxygen serves as the terminal oxidant, or cheap sacrificial oxidants are used, providing a very practical approach for generating reactive inorganic radicals for organic synthesis. We discuss in this perspective several recently reported examples: Nitrate radicals are obtained by one-electron photooxidation of nitrate anions and are very reactive toward organic molecules. The photooxidation of sulfinate salts yields the much more stable sulfone radicals, which smoothly add to double bonds. A two-electron oxidation of chloride anions to electrophilic chlorine species reacting with arenes in aromatic substitutions extends the method beyond radical reactions. The chloride anion oxidation proceeds via photocatalytically generated peracidic acid as the oxidation reagent. Although the number of reported examples of photocatalytically generated inorganic radical intermediates for organic synthesis is still small, future extension of the concept to other inorganic ions as radical precursors is a clear perspective. PMID- 27355755 TI - Deletion of P2Y2 receptor reveals a role for lymphotoxin-alpha in fatty streak formation. AB - BACKGROUND: Lymphotoxin alpha (LTalpha) is expressed in human atherosclerotic lesions and genetic variations in the LTalpha pathway have been linked to myocardial infarction. Activation of the P2Y2 nucleotide receptor (P2Y2R) regulates the production of LTalpha. in vitro. We aimed to uncover a potential pathway linking purinergic receptor to LTalpha-mediated inflammatory processes pivotal to the early stages of atherosclerosis in apolipoprotein E (ApoE(-)(/)( )) deficient mice. METHODS AND RESULTS: En face immunostaining revealed that P2Y2R and VCAM-1 are preferentially expressed in the atherosclerosis prone site of the mouse aortic sinus. Deletion of the P2Y2R gene suppresses VCAM-1 expression. Compared with ApoE(-)(/)(-) mice, ApoE(-)(/)(-) mice lacking the P2Y2R gene (ApoE(-)(/)(-)/P2Y2R(-)(/)(-)) did not develop fatty streak lesions when fed a standard chow diet for 15weeks. Systemic and CD4(+) T cell production of the pro-inflammatory cytokine lymphotoxin-alpha (LTalpha) were specifically inhibited in ApoE(-)(/)(-)/P2Y2R(-)(/)(-)mice. Anti-LTalpha preventive treatment was initiated in ApoE(-)(/)(-)mice with intraperitoneal administration of recombinant human tumor necrosis factor receptor 1 fusion protein (TNFR1-Fc) on 5 consecutive days before the disease onset. Remarkably, none of the TNFR1:Fc treated ApoE(-)(/)(-)mice exhibited atherosclerotic lesions at any developmental stage. SIGNIFICANCE: ApoE(-)(/)(-) mice deficient in P2Y2R exhibit low endothelial cell VCAM-1 levels, decreased production of LTalpha and delayed onset of atherosclerosis. These data suggest that targeting this nucleotide receptor could be an effective therapeutic approach in atherosclerosis. PMID- 27355756 TI - In vitro screening for inhibitor of cloned Drosophila melanogaster tyramine-beta hydroxylase and docking studies. AB - Biogenic amines are common biologically active substances extended within the whole animal kingdom where they play vital roles as signal transducer as well as regulator of cell functions. One of these biogenic amines called octopamine (OA) is synthesized from tyramine (TA) by the catalysis of tyramine-beta-hydroxylase (TbetaH) originated in the insect nervous system. Both TA and OA act as neurotransmitters, neurohormones and neuromodulators in the arthropod nervous system. Herein, the inhibitory activity of 1-arylimidazole-2(3H)-thiones (AITs) was tested on cloned Drosophila tyramine-beta-hydroxylase (DmTbetaH) expressed in Bombyx mori strain. Radiolabelled 3H-TA was used to analyze the activity of AITs exhibited inhibitory effects on DmTbetaH, whose ID50 values range from 0.02 to 2511nM where DmTbetaH was inhibited in a dose-dependent manner at pH 7.6 and 25 degrees C during a 30min of incubation. To understand the catalytic role of the TbetaH, a three dimensional structure of the TbetaH from Drosophila melanogaster was constructed by homology modeling using the Phyre2 web server with 100% confidence. The modeled three-dimensional structure of TbetaH was used to perform the docking study with AITs. This may give more insights to precise design of inhibitors for TbetaH to control insect's population. PMID- 27355757 TI - Purification and structural characterization of Mce4A from Mycobacterium tuberculosis. AB - The mce4A gene of Mycobacterium tuberculosis encodes a 400 amino acid residues protein of 43kDa, which is a mammalian cell entry protein (Mce4A) and plays important role in host cell invasion. Mce4A helps in long-term survival of M. tuberculosis by cholesterol utilization. Host cholesterol utilization mechanism by Mce4A is not clearly understood. In order to investigate the role of Mce4A in M. tuberculosis pathogenesis, we purified the recombinant protein by affinity chromatography, analyzed by SDS-PAGE and confirmed by western blot. We performed structural studies of Mce4A as function of pH and salt concentration by using different spectroscopic techniques. This protein was found to be stable over the wide range of pH 5.5<=pH<=11.5. An addition of sodium chloride up to the concentration of 150mM, shows no significant change in the secondary structure content of the protein. To confirm its activity, we performed isothermal titration calorimetry measurements of Mce4A in the presence of cholesterol. This is the first report of binding of cholesterol to Mce4A in vitro. Binding of cholesterol to Mce4A is sequential four-step and entropy driven process. The structural studies of this protein will help to understand the mechanism of pathogenesis of M. tuberculosis. PMID- 27355758 TI - Exploring REACH as a potential data source for characterizing ecotoxicity in life cycle assessment. AB - Toxicity models in life cycle impact assessment (LCIA) currently only characterize a small fraction of marketed substances, mostly because of limitations in the underlying ecotoxicity data. One approach to improve the current data situation in LCIA is to identify new data sources, such as the European Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH) database. The present study explored REACH as a potential data source for LCIA based on matching reported ecotoxicity data for substances that are currently also included in the United Nations Environment Programme/Society for Environmental Toxicology and Chemistry (UNEP/SETAC) scientific consensus model USEtox for characterizing toxicity impacts. Data are evaluated with respect to number of data points, reported reliability, and test duration, and are compared with data listed in USEtox at the level of hazardous concentration for 50% of the covered species per substance. The results emphasize differences between data available via REACH and in USEtox. The comparison of ecotoxicity data from REACH and USEtox shows potential for using REACH ecotoxicity data in LCIA toxicity characterization, but also highlights issues related to compliance of submitted data with REACH requirements as well as different assumptions underlying regulatory risk assessment under REACH versus data needed for LCIA. Thus, further research is required to address data quality, pre-processing, and applicability, before considering data submitted under REACH as a data source for use in LCIA, and also to explore additionally available data sources, published studies, and reports. Environ Toxicol Chem 2017;36:492-500. (c) 2016 SETAC. PMID- 27355760 TI - The Moderating Effect of Success Importance on the Relationship Between Listening Demand and Listening Effort. AB - A common element of the psychophysiological research on listening effort is the focus on listening demand as determinant of effort. The article discusses preceding studies and theorizing on effort to show that the link between listening demand and listening effort is moderated by various variables. Moreover, I will present a recent study that examined the joint effect of listening demand and success importance on effort-related cardiovascular reactivity in an auditory discrimination task. Results for pre-ejection period reactivity-an indicator of sympathetic activity-supported the hypothesis that the relationship between listening demand and listening effort is moderated by other variables: Pre-ejection period reactivity was higher in the high-demand-high success-importance condition than in the other three conditions. This new finding as well as the findings of previous research on effort suggest that a broader perspective on the determinants of listening effort is warranted. PMID- 27355761 TI - Autonomic Nervous System Reactivity During Speech Repetition Tasks: Heart Rate Variability and Skin Conductance. AB - Cognitive and emotional challenges may elicit a physiological stress response that can include arousal of the sympathetic nervous system (fight or flight response) and withdrawal of the parasympathetic nervous system (responsible for recovery and rest). This article reviews studies that have used measures of electrodermal activity (skin conductance) and heart rate variability (HRV) to index sympathetic and parasympathetic activity during auditory tasks. In addition, the authors present results from a new study with normal-hearing listeners examining the effects of speaking rate on changes in skin conductance and high-frequency HRV (HF-HRV). Sentence repetition accuracy for normal and fast speaking rates was measured in noise using signal to noise ratios that were adjusted to approximate 80% accuracy (+3 dB fast rate; 0 dB normal rate) while monitoring skin conductance and HF-HRV activity. A significant increase in skin conductance level (reflecting sympathetic nervous system arousal) and a decrease in HF-HRV (reflecting parasympathetic nervous system withdrawal) were observed with an increase in speaking rate indicating sensitivity of both measures to increased task demand. Changes in psychophysiological reactivity with increased auditory task demand may reflect differences in listening effort, but other person-related factors such as motivation and stress may also play a role. Further research is needed to understand how psychophysiological activity during listening tasks is influenced by the acoustic characteristics of stimuli, task demands, and by the characteristics and emotional responses of the individual. PMID- 27355762 TI - Cortisol, Chromogranin A, and Pupillary Responses Evoked by Speech Recognition Tasks in Normally Hearing and Hard-of-Hearing Listeners: A Pilot Study. AB - Pupillometry is one method that has been used to measure processing load expended during speech understanding. Notably, speech perception (in noise) tasks can evoke a pupil response. It is not known if there is concurrent activation of the sympathetic nervous system as indexed by salivary cortisol and chromogranin A (CgA) and whether such activation differs between normally hearing (NH) and hard of-hearing (HH) adults. Ten NH and 10 adults with mild-to-moderate hearing loss (mean age 52 years) participated. Two speech perception tests were administered in random order: one in quiet targeting 100% correct performance and one in noise targeting 50% correct performance. Pupil responses and salivary samples for cortisol and CgA analyses were collected four times: before testing, after the two speech perception tests, and at the end of the session. Participants rated their perceived accuracy, effort, and motivation. Effects were examined using repeated-measures analyses of variance. Correlations between outcomes were calculated. HH listeners had smaller peak pupil dilations (PPDs) than NH listeners in the speech in noise condition only. No group or condition effects were observed for the cortisol data, but HH listeners tended to have higher cortisol levels across conditions. CgA levels were larger at the pretesting time than at the three other test times. Hearing impairment did not affect CgA. Self rated motivation correlated most often with cortisol or PPD values. The three physiological indicators of cognitive load and stress (PPD, cortisol, and CgA) are not equally affected by speech testing or hearing impairment. Each of them seem to capture a different dimension of sympathetic nervous system activity. PMID- 27355759 TI - Is Listening in Noise Worth It? The Neurobiology of Speech Recognition in Challenging Listening Conditions. AB - This review examines findings from functional neuroimaging studies of speech recognition in noise to provide a neural systems level explanation for the effort and fatigue that can be experienced during speech recognition in challenging listening conditions. Neuroimaging studies of speech recognition consistently demonstrate that challenging listening conditions engage neural systems that are used to monitor and optimize performance across a wide range of tasks. These systems appear to improve speech recognition in younger and older adults, but sustained engagement of these systems also appears to produce an experience of effort and fatigue that may affect the value of communication. When considered in the broader context of the neuroimaging and decision making literature, the speech recognition findings from functional imaging studies indicate that the expected value, or expected level of speech recognition given the difficulty of listening conditions, should be considered when measuring effort and fatigue. The authors propose that the behavioral economics or neuroeconomics of listening can provide a conceptual and experimental framework for understanding effort and fatigue that may have clinical significance. PMID- 27355764 TI - Using Speech Recall in Hearing Aid Fitting and Outcome Evaluation Under Ecological Test Conditions. AB - In adaptive Speech Reception Threshold (SRT) tests used in the audiological clinic, speech is presented at signal to noise ratios (SNRs) that are lower than those generally encountered in real-life communication situations. At higher, ecologically valid SNRs, however, SRTs are insensitive to changes in hearing aid signal processing that may be of benefit to listeners who are hard of hearing. Previous studies conducted in Swedish using the Sentence-final Word Identification and Recall test (SWIR) have indicated that at such SNRs, the ability to recall spoken words may be a more informative measure. In the present study, a Danish version of SWIR, known as the Sentence-final Word Identification and Recall Test in a New Language (SWIRL) was introduced and evaluated in two experiments. The objective of experiment 1 was to determine if the Swedish results demonstrating benefit from noise reduction signal processing for hearing aid wearers could be replicated in 25 Danish participants with mild to moderate symmetrical sensorineural hearing loss. The objective of experiment 2 was to compare direct-drive and skin-drive transmission in 16 Danish users of bone anchored hearing aids with conductive hearing loss or mixed sensorineural and conductive hearing loss. In experiment 1, performance on SWIRL improved when hearing aid noise reduction was used, replicating the Swedish results and generalizing them across languages. In experiment 2, performance on SWIRL was better for direct-drive compared with skin-drive transmission conditions. These findings indicate that spoken word recall can be used to identify benefits from hearing aid signal processing at ecologically valid, positive SNRs where SRTs are insensitive. PMID- 27355763 TI - A Taxonomy of Fatigue Concepts and Their Relation to Hearing Loss. AB - Fatigue is common in individuals with a variety of chronic health conditions and can have significant negative effects on quality of life. Although limited in scope, recent work suggests persons with hearing loss may be at increased risk for fatigue, in part due to effortful listening that is exacerbated by their hearing impairment. However, the mechanisms responsible for hearing loss-related fatigue, and the efficacy of audiologic interventions for reducing fatigue, remain unclear. To improve our understanding of hearing loss-related fatigue, as a field it is important to develop a common conceptual understanding of this construct. In this article, the broader fatigue literature is reviewed to identify and describe core constructs, consequences, and methods for assessing fatigue and related constructs. Finally, the current knowledge linking hearing loss and fatigue is described and may be summarized as follows: Hearing impairment may increase the risk of subjective fatigue and vigor deficits; adults with hearing loss require more time to recover from fatigue after work and have more work absences; sustained, effortful, listening can be fatiguing; optimal methods for eliciting and measuring fatigue in persons with hearing loss remain unclear and may vary with listening condition; and amplification may minimize decrements in cognitive processing speed during sustained effortful listening. Future research is needed to develop reliable measurement methods to quantify hearing loss-related fatigue, explore factors responsible for modulating fatigue in people with hearing loss, and identify and evaluate potential interventions for reducing hearing loss-related fatigue. PMID- 27355766 TI - Eriksholm Workshop on Hearing Impairment and Cognitive Energy. PMID- 27355767 TI - Effort and Displeasure in People Who Are Hard of Hearing. AB - Listening effort helps explain why people who are hard of hearing are prone to fatigue and social withdrawal. However, a one-factor model that cites only effort due to hardness of hearing is insufficient as there are many who lead happy lives despite their disability. This article explores other contributory factors, in particular motivational arousal and pleasure. The theory of rational motivational arousal predicts that some people forego listening comprehension because they believe it to be impossible and hence worth no effort at all. This is problematic. Why should the listening task be rated this way, given the availability of aids that reduce its difficulty? Two additional factors narrow the explanatory gap. First, we separate the listening task from the benefit derived as a consequence. The latter is temporally more distant, and is discounted as a result. The second factor is displeasure attributed to the listening task, which increases listening cost. Many who are hard of hearing enjoy social interaction. In such cases, the actual activity of listening is a benefit, not a cost. These people also reap the benefits of listening, but do not have to balance these against the displeasure of the task. It is suggested that if motivational harmony can be induced by training in somebody who is hard of hearing, then the obstacle to motivational arousal would be removed. This suggests a modified goal for health care professionals. Do not just teach those who are hard of hearing how to use hearing assistance devices. Teach them how to do so with pleasure and enjoyment. PMID- 27355768 TI - Evolution of Models of Working Memory and Cognitive Resources. AB - The goal of this article is to trace the evolution of models of working memory and cognitive resources from the early 20th century to today. Linear flow models of information processing common in the 1960s and 1970s centered on the transfer of verbal information from a limited-capacity short-term memory store to long term memory through rehearsal. Current conceptions see working memory as a dynamic system that includes both maintaining and manipulating information through a series of interactive components that include executive control and attentional resources. These models also reflect the evolution from an almost exclusive concentration on working memory for verbal materials to inclusion of a visual working memory component. Although differing in postulated mechanisms and emphasis, these evolving viewpoints all share the recognition that human information processing is a limited-capacity system with limits on the amount of information that can be attended to, remain activated in memory, and utilized at one time. These limitations take on special importance in spoken language comprehension, especially when the stimuli have complex linguistic structures or listening effort is increased by poor acoustic quality or reduced hearing acuity. PMID- 27355765 TI - Listening and Learning: Cognitive Contributions to the Rehabilitation of Older Adults With and Without Audiometrically Defined Hearing Loss. AB - Here, we describe some of the ways in which aging negatively affects the way sensory input is transduced and processed within the aging brain and how cognitive work is involved when listening to a less-than-perfect signal. We also describe how audiologic rehabilitation, including hearing aid amplification and listening training, is used to reduce the amount of cognitive resources required for effective auditory communication and conclude with an example of how listening effort is being studied in research laboratories for the purpose(s) of informing clinical practice. PMID- 27355769 TI - The Implications of Cognitive Aging for Listening and the Framework for Understanding Effortful Listening (FUEL). AB - This review article considers some of the age-related changes in cognition that are likely to interact with hearing, listening effort, and cognitive energy. The focus of the review is on normative age-related changes in cognition; however, consideration is also given to older adults who experience clinically significant deficits in cognition, such as persons with Alzheimer's disease or who may be in a preclinical stage of dementia (mild cognitive impairment). The article distinguishes between the assessment of cognitive function for clinical versus research purposes. It reviews the goal of cognitive testing in older adults and discusses the challenges of validly assessing cognition in persons with sensory impairments. The article then discusses the goals of assessing specific cognitive functions (processing speed and attentional processes) for the purpose of understanding their relationships with listening effort. Finally, the article highlights certain concepts that are likely to be relevant to listening effort and cognitive energy, including some issues that have not yet received much attention in this context (e.g., conation, cognitive reserve, and second language speech processing). PMID- 27355771 TI - Hearing Impairment and Cognitive Energy: The Framework for Understanding Effortful Listening (FUEL). AB - The Fifth Eriksholm Workshop on "Hearing Impairment and Cognitive Energy" was convened to develop a consensus among interdisciplinary experts about what is known on the topic, gaps in knowledge, the use of terminology, priorities for future research, and implications for practice. The general term cognitive energy was chosen to facilitate the broadest possible discussion of the topic. It goes back to who described the effects of attention on perception; he used the term psychic energy for the notion that limited mental resources can be flexibly allocated among perceptual and mental activities. The workshop focused on three main areas: (1) theories, models, concepts, definitions, and frameworks; (2) methods and measures; and (3) knowledge translation. We defined effort as the deliberate allocation of mental resources to overcome obstacles in goal pursuit when carrying out a task, with listening effort applying more specifically when tasks involve listening. We adapted Kahneman's seminal (1973) Capacity Model of Attention to listening and proposed a heuristically useful Framework for Understanding Effortful Listening (FUEL). Our FUEL incorporates the well-known relationship between cognitive demand and the supply of cognitive capacity that is the foundation of cognitive theories of attention. Our FUEL also incorporates a motivation dimension based on complementary theories of motivational intensity, adaptive gain control, and optimal performance, fatigue, and pleasure. Using a three-dimensional illustration, we highlight how listening effort depends not only on hearing difficulties and task demands but also on the listener's motivation to expend mental effort in the challenging situations of everyday life. PMID- 27355770 TI - Sensory-Cognitive Interactions in Older Adults. AB - The objective of this study was regarding sensory and cognitive interactions in older adults published since 2009, the approximate date of the most recent reviews on this topic. After an electronic database search of articles published in English since 2009 on measures of hearing and cognition or vision and cognition in older adults, a total of 437 articles were identified. Screening by title and abstract for appropriateness of topic and for articles presenting original research in peer-reviewed journals reduced the final number of articles reviewed to 34. These articles were qualitatively evaluated and synthesized with the existing knowledge base. Additional evidence has been obtained since 2009 associating declines in vision, hearing, or both with declines in cognition among older adults. The observed sensory-cognitive associations are generally stronger when more than one sensory domain is measured and when the sensory measures involve more than simple threshold sensitivity. Evidence continues to accumulate supporting a link between decline in sensory function and cognitive decline in older adults. PMID- 27355773 TI - Cognitive Spare Capacity as an Index of Listening Effort. AB - Everyday listening may be experienced as effortful, especially by individuals with hearing loss. This may be due to internal factors, such as cognitive load, and external factors, such as noise. Even when speech is audible, internal and external factors may combine to reduce cognitive spare capacity, or the ability to engage in cognitive processing of spoken information. A better understanding of cognitive spare capacity and how it can be optimally allocated may guide new approaches to rehabilitation and ultimately improve outcomes. This article presents results of three tests of cognitive spare capacity:1. Sentence-final Word Identification and Recall (SWIR) test2. Cognitive Spare Capacity Test (CSCT)3. Auditory Inference Span Test (AIST)Results show that noise reduces cognitive spare capacity even when speech intelligibility is retained. In addition, SWIR results show that hearing aid signal processing can increase cognitive spare capacity, and CSCT and AIST results show that increasing load reduces cognitive spare capacity. Correlational evidence suggests that while the effect of noise on cognitive spare capacity is related to working memory capacity, the effect of load is related to executive function. Future studies should continue to investigate how hearing aid signal processing can mitigate the effect of load on cognitive spare capacity, and whether such effects can be enhanced by developing executive skills through training. The mechanisms modulating cognitive spare capacity should be investigated by studying their neural correlates, and tests of cognitive spare capacity should be developed for clinical use in conjunction with developing new approaches to rehabilitation. PMID- 27355772 TI - Listening Effort in Younger and Older Adults: A Comparison of Auditory-Only and Auditory-Visual Presentations. AB - One goal of the present study was to establish whether providing younger and older adults with visual speech information (both seeing and hearing a talker compared with listening alone) would reduce listening effort for understanding speech in noise. In addition, we used an individual differences approach to assess whether changes in listening effort were related to changes in visual enhancement-the improvement in speech understanding in going from an auditory only (A-only) to an auditory-visual condition (AV) condition. To compare word recognition in A-only and AV modalities, younger and older adults identified words in both A-only and AV conditions in the presence of six-talker babble. Listening effort was assessed using a modified version of a serial recall task. Participants heard (A-only) or saw and heard (AV) a talker producing individual words without background noise. List presentation was stopped randomly and participants were then asked to repeat the last three words that were presented. Listening effort was assessed using recall performance in the two- and three-back positions. Younger, but not older, adults exhibited reduced listening effort as indexed by greater recall in the two- and three-back positions for the AV compared with the A-only presentations. For younger, but not older adults, changes in performance from the A-only to the AV condition were moderately correlated with visual enhancement. Results are discussed within a limited resource model of both A-only and AV speech perception. PMID- 27355774 TI - Cognitive Load and Listening Effort: Concepts and Age-Related Considerations. AB - Listening effort has been recognized as an important dimension of everyday listening, especially with regard to the comprehension of spoken language. At constant levels of comprehension performance, the level of effort exerted and perceived during listening can differ considerably across listeners and situations. In this article, listening effort is used as an umbrella term for two different types of effort that can arise during listening. One of these types is processing effort, which is used to denote the utilization of "extra" mental processing resources in listening conditions that are adverse for an individual. A conceptual description is introduced how processing effort could be defined in terms of situational influences, the listener's auditory and cognitive resources, and the listener's personal state. Also, the proposed relationship between processing effort and subjectively perceived listening effort is discussed. Notably, previous research has shown that the availability of mental resources, as well as the ability to use them efficiently, changes over the course of adult aging. These common age-related changes in cognitive abilities and their neurocognitive organization are discussed in the context of the presented concept, especially regarding situations in which listening effort may be increased for older people. PMID- 27355775 TI - A Model of Auditory-Cognitive Processing and Relevance to Clinical Applicability. AB - Hearing loss and cognitive function interact in both a bottom-up and top-down relationship. Listening effort is tied to these interactions, and models have been developed to explain their relationship. The Ease of Language Understanding model in particular has gained considerable attention in its explanation of the effect of signal distortion on speech understanding. Signal distortion can also affect auditory scene analysis ability, however, resulting in a distorted auditory scene that can affect cognitive function, listening effort, and the allocation of cognitive resources. These effects are explained through an addition to the Ease of Language Understanding model. This model can be generalized to apply to all sounds, not only speech, representing the increased effort required for auditory environmental awareness and other nonspeech auditory tasks. While the authors have measures of speech understanding and cognitive load to quantify these interactions, they are lacking measures of the effect of hearing aid technology on auditory scene analysis ability and how effort and attention varies with the quality of an auditory scene. Additionally, the clinical relevance of hearing aid technology on cognitive function and the application of cognitive measures in hearing aid fittings will be limited until effectiveness is demonstrated in real-world situations. PMID- 27355776 TI - How Social Psychological Factors May Modulate Auditory and Cognitive Functioning During Listening. AB - The framework for understanding effortful listening (FUEL) draws on psychological theories of cognition and motivation. In the present article, theories of social cognitive psychology are related to the FUEL. Listening effort is defined in our consensus as the deliberate allocation of mental resources to overcome obstacles in goal pursuit when carrying out a task that involves listening. Listening effort depends not only on hearing difficulties and task demands but also on the listener's motivation to expend mental effort in challenging situations. Listeners' cost/benefit evaluations involve appraisals of listening demands, their own capacity, and the importance of listening goals. Social psychological factors can affect a listener's actual and self-perceived auditory and cognitive abilities, especially when those abilities may be insufficient to readily meet listening demands. Whether or not listeners experience stress depends not only on how demanding a situation is relative to their actual abilities but also on how they appraise their capacity to meet those demands. The self-perception or appraisal of one's abilities can be lowered by poor self-efficacy or negative stereotypes. Stress may affect performance in a given situation and chronic stress can have deleterious effects on many aspects of health, including auditory and cognitive functioning. Social support can offset demands and mitigate stress; however, the burden of providing support may stress the significant other. Some listeners cope by avoiding challenging situations and withdrawing from social participation. Extending the FUEL using social-cognitive psychological theories may provide valuable insights into how effortful listening could be reduced by adopting health-promoting approaches to rehabilitation. PMID- 27355777 TI - Folliculin - A tumor suppressor at the intersection of metabolic signaling and membrane traffic. AB - The Birt-Hoge-Dube syndrome tumor suppressor Folliculin is a regulator of metabolism and has as a wide range of cellular and organismal phenotypes associated with its disruption. However, the molecular mechanisms which underlie its functions are poorly understood. Folliculin has been described to associate with lysosomes in response to nutrient depletion and form a key part of the signaling network that controls the activity of mTORC1. We recently reported that Folliculin can control the nutrient dependent cytoplasmic distribution of lysosomes by promoting the formation of a complex with the Golgi-associated small GTPase Rab34 and its effector RILP. We thus define a mechanistic connection between the lysosomal nutrient signaling network and the transport machinery that controls the distribution and dynamics of this organelle. Here we summarise the main conclusions from that study, attempt to integrate our findings with other recent studies on lysosome distribution/dynamics, and discuss the potential consequences of the dysregulation of this processes caused by Folliculin loss for Birt-Hoge-Dube syndrome and normal cell function. PMID- 27355778 TI - The ABMS MOC Part III Examination: Value, Concerns, and Alternative Formats. AB - This article describes the presentations and discussions at a conference co convened by the Council on Medical Education of the American Medical Association (AMA) and by the American Board of Medical Specialties (ABMS). The conference focused on the ABMS Maintenance of Certification (MOC) Part III Examination. This article, reflecting the conference agenda, covers the value of and evidence supporting the examination, as well as concerns about the cost of the examination, and-given the current format-its relevance. In addition, the article outlines alternative formats for the examination that four ABMS member boards are currently developing or implementing. Lastly, the article presents contrasting views on the approach to professional self-regulation. One view operationalizes MOC as a high-stakes, pass-fail process while the other perspective holds MOC as an organized approach to support continuing professional development and improvement. The authors hope to begin a conversation among the AMA, the ABMS, and other professional stakeholders about how knowledge assessment in MOC might align with the MOC program's educational and quality improvement elements and best meet the future needs of both the public and the physician community. PMID- 27355779 TI - Common Evaluation Designs in Medical Education II. PMID- 27355780 TI - Entrusting Observable Practice Activities and Milestones Over the 36 Months of an Internal Medicine Residency. AB - PURPOSE: Competency-based medical education and milestone reporting have led to increased interest in work-based assessments using entrustment over time as an assessment framework. Little is known about data collected from these assessments during residency. This study describes the results of entrustment of discrete work-based skills over 36 months in the University of Cincinnati internal medicine (IM) residency program. METHOD: Attending physician and peer/allied health assessors provided entrustment ratings of resident performance on work based observable practice activities (OPAs) mapped to Accreditation Council for Graduate Medicine Education/American Board of Internal Medicine reporting milestones for IM. These data were translated into milestones data and tracked longitudinally. The authors analyzed data from this new entrustment system's first 36 months (July 2012-June 2015). RESULTS: During the 36-month period, assessors made 364,728 milestone assessments (mapped from OPAs) of 189 residents. Residents received an annualized average of 83 assessment encounters, producing means of 3,987 milestone assessments and 4,325 words of narrative assessment. Mean entrustment ratings (range 1-5) from all assessors for all milestones rose from 2.46 for first-month residents to 3.92 for 36th-month residents (r = 0.9252, P < .001). Attending physicians' entrustment ratings were lower than peer/allied health assessors' ratings. Medical knowledge and patient care milestones were rated lower than professionalism and interpersonal and communication skills milestones. CONCLUSIONS: Entrustment of milestones appears to rise progressively over time, with differences by assessor type, competency, milestone, and resident. Further research is needed to elucidate the validity of these data in promotion, remediation, and reporting decisions. PMID- 27355781 TI - A Framework for Understanding Lapses in Professionalism Among Medical Students: Applying the Theory of Planned Behavior to Fitness to Practice Cases. AB - Fitness to practice decisions are often based on a student's digression from the regulations, with limited exploration of the reasoning behind the student's behavior. However, behavior is underpinned by complex, "hidden" variables, including an individual's attitudes and social norms. Examining hidden determinants of professionalism, such as context, interpersonal relationships, social norms, and local cultures, then allows medical educators to develop a richer understanding of unprofessional behavior.In this article, the authors propose the use of the theory of planned behavior (TPB) as a framework to help evaluate unprofessional behavior in students. The TPB is a deliberative processing model that explains how an individual's behavior is underpinned by his or her cognitions, with behavior being primarily dependent on the intention to perform the behavior (behavioral intention). Intention, in turn, is determined by three variables: attitude, subjective norm, and perceived behavioral control.To understand the practical use of the TPB, the authors present four complex, anonymized case studies in which they employed the TPB to help deal with serious professionalism lapses among medical students. The outcomes of these cases as well as the student and program director perspectives, all explained via the TPB variables, are presented. The strengths and limitations of the TPB are discussed. PMID- 27355782 TI - Addressing Authorship Issues Prospectively: A Heuristic Approach. AB - Collaborative writing in academic medicine gives rise to more richly informed scholarship, and yet challenging ethical issues surrounding authorship are commonly encountered. International guidelines on authorship help clarify whether individuals who have contributed to a completed scholarly work have been correctly included as authors, but these guidelines do not facilitate intentional and proactive authorship planning or decisions regarding authorship order.In this Commentary, the author presents a heuristic approach to help collaborators clarify, anticipate, and resolve practical and ethically important authorship issues as they engage in the process of developing manuscripts. As this approach illustrates, assignment of authorship should balance work effort and professional responsibility, reflecting the effort and intellectual contribution and the public accountability of the individuals who participate in the work. Using a heuristic approach for managing authorship issues prospectively can foster an ethical, collaborative writing process in which individuals are properly recognized for their contributions. PMID- 27355783 TI - Modifying the Primary Care Exception Rule to Require Competency-Based Assessment. AB - Teaching residents to practice independently is a core objective of graduate medical education (GME). However, billing rules established by the Centers for Medicare and Medicaid Services (CMS) require that teaching physicians physically be present in the examination room for the care they bill, unless the training program qualifies for the Primary Care Exception Rule (PCER). Teaching physicians in programs that use this exception can bill for indirectly supervised ambulatory care once the resident who provides that care has completed six months of training. However, CMS does not mandate that programs assess or attest to residents' clinical competence before using this rule. By requiring this six month probationary period, the implication is that residents are adequately prepared for indirectly supervised practice by this time. As residents' skill development varies, this may or may not be true. The PCER makes no attempt to delineate how residents' competence should be assessed, nor does the GME community have a standard for how and when to make this assessment specifically for the purpose of determining residents' readiness for indirectly supervised primary care practice.In this Perspective, the authors review the history and current requirements of the PCER, explore its limitations, and offer suggestions for how to modify the teaching physician billing requirements to mandate the evaluation of residents' competence using the existing milestones framework. They also recommend strategies to standardize this process of evaluation and to develop benchmarks across training programs. PMID- 27355784 TI - Peer Support for Clinicians: A Programmatic Approach. AB - Burnout is plaguing the culture of medicine and is linked to several primary causes including long work hours, increasingly burdensome documentation, and resource constraints. Beyond these, additional emotional stressors for physicians are involvement in an adverse event, especially one that involves a medical error, and malpractice litigation. The authors argue that it is imperative that health care institutions devote resources to programs that support physician well being and resilience. Doing so after adverse and other emotionally stressful events, such as the death of a colleague or caring for victims of a mass trauma, is crucial as clinicians are often at their most vulnerable during such times. To this end, the Center for Professionalism and Peer Support at Brigham and Women's Hospital redesigned the peer support program in 2009 to provide one-on-one peer support. The peer support program was one of the first of its kind; over 25 national and international programs have been modeled off of it. This Perspective describes the origin, structure, and basic workings of the peer support program, including important components for the peer support conversation (outreach call, invitation/opening, listening, reflecting, reframing, sense-making, coping, closing, and resources/referrals). The authors argue that creating a peer support program is one way forward, away from a culture of invulnerability, isolation, and shame and toward a culture that truly values a sense of shared organizational responsibility for clinician well-being and patient safety. PMID- 27355785 TI - Recognizing Privilege and Bias: An Interactive Exercise to Expand Health Care Providers' Personal Awareness. AB - PROBLEM: Despite increasing awareness of the social determinants of health, health care disparities among sociocultural groups persist. Health care providers' unconscious bias resulting from unrecognized social privilege is one contributor to these disparities. APPROACH: In 2009, Henry Ford Health System initiated the Healthcare Equity Campaign both to raise employees' awareness of inequalities related to the social determinants of health and to increase their motivation to reduce them. After conducting awareness-raising activities to increase employees' understanding of the social determinants of health, a curriculum team developed the interactive Privilege and Responsibility Curricular Exercise (PRCE) and incorporated it into a series of trainings. The team designed the exercise to enhance participants' awareness of privilege in their lives and work, to improve their understanding of the impact of privilege on their own and others' lived experiences as a step beyond cultural competence toward cultural humility, and to encourage them to leverage their advantages to reduce health care inequities. OUTCOMES: About 300 participants of diverse professional and personal backgrounds from across the health system completed the training between the spring of 2009 and the spring of 2012, and many provided qualitative feedback about the exercise. Evaluations showed the exercise's potential as a powerful learning experience that might enhance a variety of equity- or diversity-related trainings, and also showed that participants considered the PRCE a highlight of the training. NEXT STEPS: The PRCE is worthy of additional study and could prove valuable to other organizations. PMID- 27355787 TI - CEP-1 is pro-choice for reproductive health in C. elegans. PMID- 27355786 TI - Effects of Methyl Substitution in Ruthenium Tris(2-pyridylmethyl)amine Photocaging Groups for Nitriles. AB - Four complexes of the general formula [Ru(L)(CH3CN)2](PF6)2, [L = TPA (5), MeTPA (6), Me2TPA (7), and Me3TPA (8)] [TPA = tris[(pyridin-2-yl)methyl]amine, where methyl groups were introduced consecutively onto the 6-position of py donors of TPA, were prepared and characterized by various spectroscopic techniques and mass spectrometry. While 5 and 8 were isolated as single stereoisomers, 6 and 7 were isolated as mixtures of stereoisomers in 2:1 and 1.5:1 ratios, respectively. Steric effects on ground state stability and thermal and photochemical reactivities were studied for all four complexes using (1)H NMR and electronic absorption spectroscopies and computational studies. These studies confirmed that the addition of steric bulk accelerates photochemical and thermal nitrile release. PMID- 27355788 TI - Ptosis, Miosis, and Intermittent Esotropia Following Pituitary Adenoma Resection. PMID- 27355789 TI - Five-State Molecular Shuttling of a Pair of [2]Rotaxanes: Distinct Outputs in Response to Acid and Base Stimuli. AB - In this study we synthesized two acid-/base-controllable [2]rotaxanes featuring aminodiazobenzene and aminocoumarin units, respectively, as chromophores and dibenzo[24]crown-8 and dibenzo[25]crown-8 units, respectively, as their macrocyclic components. Each [2]rotaxane contained N-alkylarylamine (ammonium) and N,N-dialkylamine (ammonium) centers as binding sites for their crown ether components. The absorption patterns of the chromophores were dependent on the position of the encircling macrocyclic component and the degree of protonation, with three distinct states (under acidic, neutral, and basic conditions) evident for each [2]rotaxane. The mixed [2]rotaxane system displayed stepwise and independent molecular shuttling behavior based on the degree of protonation of the amino groups in response to both the amount and strength of added acids or bases; as such, the system provided five different absorption signals as outputs that could be read using UV/Vis spectroscopy. PMID- 27355791 TI - Plants: a tool box of cell-based assays. PMID- 27355790 TI - Total Synthesis, Structure, and Biological Activity of Adenosylrhodibalamin, the Non-Natural Rhodium Homologue of Coenzyme B12. AB - B12 is unique among the vitamins as it is biosynthesized only by certain prokaryotes. The complexity of its synthesis relates to its distinctive cobalt corrin structure, which is essential for B12 biochemistry and renders coenzyme B12 (AdoCbl) so intriguingly suitable for enzymatic radical reactions. However, why is cobalt so fit for its role in B12 -dependent enzymes? To address this question, we considered the substitution of cobalt in AdoCbl with rhodium to generate the rhodium analogue 5'-deoxy-5'-adenosylrhodibalamin (AdoRbl). AdoRbl was prepared by de novo total synthesis involving both biological and chemical steps. AdoRbl was found to be inactive in vivo in microbial bioassays for methionine synthase and acted as an in vitro inhibitor of an AdoCbl-dependent diol dehydratase. Solution NMR studies of AdoRbl revealed a structure similar to that of AdoCbl. However, the crystal structure of AdoRbl revealed a conspicuously better fit of the corrin ligand for Rh(III) than for Co(III) , challenging the current views concerning the evolution of corrins. PMID- 27355792 TI - Genotyping tumor clones from single-cell data. PMID- 27355793 TI - Biophenols from Table Olive cv Bella di Cerignola: Chemical Characterization, Bioaccessibility, and Intestinal Absorption. AB - In this study, the naturally debittered table olives cv Bella di Cerignola were studied in order to (i) characterize their phenolic composition; (ii) evaluate the polyphenols bioaccessibility; (iii) assess their absorption and transport, across Caco2/TC7. LC-MS/MS analysis has confirmed the presence of hydroxytyrosol acetate, caffeoyl-6'-secologanoside, and comselogoside. In vitro bioaccessibility ranged from 7% of luteolin to 100% of tyrosol, highlighting the flavonoids sensitivity to the digestive conditions. The Caco2/TC7 polyphenols accumulation was rapid (60 min) with an efficiency of 0.89%; the overall bioavailability was 1.86% (120 min), with hydroxytyrosol and tyrosol the highest bioavailables, followed by verbascoside and luteolin. In the cells and basolateral side, caffeic and coumaric acids metabolites, probably derived from esterase activities, were detected. In conclusion, the naturally debittered table olives cv Bella di Cerignola can be considered as a source of bioaccessible, absorbable, and bioavailable polyphenols that, for their potential health promoting effect, permit inclusion of table olives as a functional food suitable for a balanced diet. PMID- 27355794 TI - Refaunation and the reinstatement of the seed-dispersal function in Gorongosa National Park. AB - Large animals are important seed dispersers; however, they tend to be under a high extinction risk worldwide. There is compelling evidence that the global biodiversity crisis is leading to the deterioration of several ecosystem functions, but there is virtually no information on how large-scale refaunation efforts can reinstate seed dispersal. We evaluated the effectiveness of a 62-km2 wildlife sanctuary, which was established to recover populations of large mammals in Gorongosa National Park (Mozambique), in restoring seed dispersal. We collected animal scats during the dry season of 2014 (June-August) along 5 transects inside and 5 transects outside the sanctuary fence (50 km total) with the same type of plant community, identified animal and plant species in the transects, and quantified the number of seeds in each scat. Based on these data, we built bipartite networks and calculated network and species-level descriptor values, and we compared data collected inside and outside the sanctuary. There were more scats (268 vs. 207) and more scats containing seeds (132 vs. 94) inside than outside the sanctuary. The number of mammal dispersers was also higher inside (17) than outside the sanctuary (11). Similarly, more seeds (2413 vs. 2124) and plant species (33 vs. 26) were dispersed inside than outside the sanctuary. Overall, the seed-dispersal network was less specialized (0.38 vs. 0.44) and there was a greater overlap (0.16 vs. 0.07) inside than outside the sanctuary. Both networks were significantly modular and antinested. The high number and richness of seeds dispersed inside the sanctuary was explained mostly by a higher abundance of dispersers rather than by disperser identity. Our results suggest conservation efforts aimed at recovering populations of large mammals are helping to reestablish not only target mammal species but also their functional roles as seed dispersers in the ecosystem. PMID- 27355795 TI - A Prospective Open-Label Trial of Memantine Hydrochloride for the Treatment of Social Deficits in Intellectually Capable Adults With Autism Spectrum Disorder: Erratum. PMID- 27355796 TI - Relation of the Allelic Variants of Multidrug Resistance Gene to Agranulocytosis Associated With Clozapine: Erratum. PMID- 27355797 TI - Salute to Our Reviewers. PMID- 27355798 TI - New findings about atherosclerosis in Brazil from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). PMID- 27355799 TI - Frequency of cholecystectomy and associated sociodemographic and clinical risk factors in the ELSA-Brasil study. AB - CONTEXT AND OBJECTIVE: There are few data in the literature on the frequency of cholecystectomy in Brazil. The frequency of cholecystectomy and associated risk factors were evaluated in the Brazilian Longitudinal Study of Adult Health (ELSA Brasil). DESIGN AND SETTING: Cross-sectional study using baseline data on 5061 participants in Sao Paulo. METHODS: The frequency of cholecystectomy and associated risk factors were evaluated over the first two years of follow-up of the study and over the course of life. A multivariate regression analysis was presented: odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: A total of 4716 individuals (93.2%) with information about cholecystectomy were included. After two years of follow-up, 56 had undergone surgery (1.2%: 1.7% of the women; 0.6% of the men). A total of 188 participants underwent cholecystectomy during their lifetime. The risk factors associated with surgery after the two-year follow-up period were female sex (OR, 2.85; 95% CI, 1.53-5.32), indigenous ethnicity (OR, 2.1; 95% CI, 2.28-15.85) and body mass index (BMI) (OR, 1.10; 95% CI, 1.01-1.19 per 1 kg/m2 increase). The risk factors associated over the lifetime were age (OR, 1.03; 95% CI, 1.02-1.05 per one year increase), diabetes (OR, 1.92; 95% CI, 1.34-2.76) and previous bariatric surgery (OR, 5.37; 95% CI, 1.53-18.82). No association was found with parity or fertile age. CONCLUSION: Female sex and high BMI remained as associated risk factors while parity and fertile age lost significance. New factors such as bariatric surgery and indigenous ethnicity have gained importance in this country. PMID- 27355800 TI - Prevalence of stunting and overweight/obesity among Brazilian children according to different epidemiological scenarios: systematic review and meta-analysis. AB - CONTEXT AND OBJECTIVE: Within the Brazilian nutritional panorama, coexistence of antagonistic nutritional disorders can be seen, especially the increasing prevalence of overweight and the persistence of significant rates of chronic malnutrition in vulnerable groups of the population. Because these are major public health problems, this study aimed to ascertain the prevalence of stunting and overweight/obesity among Brazilian children according to different epidemiological scenarios. DESIGN AND SETTING: This was a systematic review of prevalence studies, developed at the State University of Paraiba. METHODS: The SciELO, Lilacs and PubMed databases were searched for articles, using specific keywords. Articles published between 2006 and 2014 were selected. The review was conducted by two reviewers who worked independently. A systematic review with meta-analysis was conducted, for which the studies were grouped within different epidemiological settings. RESULTS: Among the 33 articles recovered, 9 involved samples from daycare centers, 4 had samples from public healthcare services or social registers, 5 related to populations in situations of social inequity and 15 were population-based. Higher chances of stunting were found in populations in situations of social inequity and in those at public healthcare services or on social registers, in relation to reference populations. For overweight/obesity, none of the scenarios had a higher chance than the reference. CONCLUSION: Among Brazilian children, stunting continues to be a socially determined public health problem that mainly affects marginalized populations. This problem coexists with significant rates of overweight/obesity affecting all social groups. PMID- 27355801 TI - Paracoccidioidomycosis in the spine: case report and review of the literature. AB - CONTEXT:: Paracoccidioidomycosis is a systemic form of mycosis that spreads hematogenously, secondarily to reactivation of lung infection or infection at another site or to new exposure to the causative agent. Few cases of bone involvement have been reported in the literature and involvement of the spine is extremely rare. CASE REPORT:: We describe a case of a 68-year-old male patient with spondylodiscitis at the levels L4-L5 caused by presence of the fungus Paracoccidioides brasiliensis, which was diagnosed through percutaneous biopsy. The patient was treated with sulfamethoxazole and trimethoprim for 36 months, with complete resolution of the symptoms. CONCLUSION:: Spondylodiscitis caused by the fungus Paracoccidioides brasiliensis is uncommon. However, in patients with chronic low-back pain who live or used to live in endemic regions, this infection should be considered as a possible differential diagnosis. PMID- 27355802 TI - Antibiotics for mastitis in breastfeeding women. AB - BACKGROUND: Mastitis can be caused by ineffective positioning of the baby at the breast or restricted feeding. Infective mastitis is commonly caused by Staphylococcus aureus . The prevalence of mastitis in breastfeeding women may reach 33%. Effective milk removal, pain medication and antibiotic therapy have been the mainstays of treatment. OBJECTIVES: This review aims to examine the effectiveness of antibiotic therapies in relieving symptoms for breastfeeding women with mastitis with or without laboratory investigation. MAIN RESULTS: Two trials met the inclusion criteria. One small trial (n = 25) compared amoxicillin with cephradine and found no significant difference between the two antibiotics in terms of symptom relief and abscess formation. Another, older study compared breast emptying alone as 'supportive therapy' versus antibiotic therapy plus supportive therapy, and no therapy. The findings of the latter study suggested faster clearance of symptoms for women using antibiotics, although the study design was problematic. AUTHORS CONCLUSIONS: There is insufficient evidence to confirm or refute the effectiveness of antibiotic therapy for the treatment of lactational mastitis. There is an urgent need to conduct high-quality, double blinded RCTs to determine whether antibiotics should be used in this common postpartum condition. PMID- 27355803 TI - Vitamin D supplementation for women during pregnancy. AB - BACKGROUND: Vitamin D deficiency or insufficiency is thought to be common among pregnant women. Vitamin D supplementation during pregnancy has been suggested as an intervention to protect against adverse pregnancy outcomes. OBJECTIVES: To examine whether oral supplements with vitamin D alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve maternal and neonatal outcomes. MAIN RESULTS: In this updated review we included 15 trials assessing a total of 2833 women, excluded 27 trials, and 23 trials are still ongoing or unpublished. Nine trials compared the effects of vitamin D alone versus no supplementation or a placebo and six trials compared the effects of vitamin D and calcium with no supplementation. Risk of bias in the majority of trials was unclear and many studies were at high risk of bias for blinding and attrition rates.Vitamin D alone versus no supplementation or a placeboData from seven trials involving 868 women consistently show that women who received vitamin D supplements alone, particularly on a daily basis, had higher 25-hydroxyvitamin D than those receiving no intervention or placebo, but this response was highly heterogeneous. Also, data from two trials involving 219 women suggest that women who received vitamin D supplements may have a lower risk of pre-eclampsia than those receiving no intervention or placebo (8.9% versus 15.5%; risk ratio (RR) 0.52; 95% CI 0.25 to 1.05, low quality). Data from two trials involving 219 women suggest a similar risk of gestational diabetes among those taking vitamin D supplements or no intervention/placebo (RR 0.43; 95% CI 0.05, 3.45, very low quality). There were no clear differences in adverse effects, with only one reported case of nephritic syndrome in the control group in one study (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women, low quality). Given the scarcity of data for this outcome, no firm conclusions can be drawn. No other adverse effects were reported in any of the other studies.With respect to infant outcomes, data from three trials involving 477 women suggest that vitamin D supplementation during pregnancy reduces the risk preterm birth compared to no intervention or placebo (8.9% versus 15.5%; RR 0.36; 95% CI 0.14 to 0.93, moderate quality). Data from three trials involving 493 women also suggest that women who receive vitamin D supplements during pregnancy less frequently had a baby with a birthweight below 2500 g than those receiving no intervention or placebo (RR 0.40; 95% CI 0.24 to 0.67, moderate quality).In terms of other outcomes, there were no clear differences in caesarean section (RR 0.95; 95% CI 0.69 to 1.31; two trials; 312 women); stillbirths (RR 0.35 95% CI 0.06, 1.99; three trials, 540 women); or neonatal deaths (RR 0.27; 95% CI 0.04, 1.67; two trials, 282 women). There was some indication that vitamin D supplementation increases infant length (mean difference (MD) 0.70, 95% CI -0.02 to 1.43; four trials, 638 infants) and head circumference at birth (MD 0.43, 95% CI 0.03 to 0.83; four trials, 638 women).Vitamin D and calcium versus no supplementation or a placeboWomen who received vitamin D with calcium had a lower risk of pre eclampsia than those not receiving any intervention (RR 0.51; 95% CI 0.32 to 0.80; three trials; 1114 women, moderate quality), but also an increased risk of preterm birth (RR 1.57; 95% CI 1.02 to 2.43, three studies, 798 women, moderate quality). Maternal vitamin D concentration at term, gestational diabetes, adverse effects and low birthweight were not reported in any trial or reported only by one study. AUTHORS CONCLUSIONS: New studies have provided more evidence on the effects of supplementing pregnant women with vitamin D alone or with calcium on pregnancy outcomes. Supplementing pregnant women with vitamin D in a single or continued dose increases serum 25-hydroxyvitamin D at term and may reduce the risk of pre-eclampsia, low birthweight and preterm birth. However, when vitamin D and calcium are combined, the risk of preterm birth is increased. The clinical significance of the increased serum 25-hydroxyvitamin D concentrations is still unclear. In light of this, these results need to be interpreted with caution. Data on adverse effects were lacking in all studies.The evidence on whether vitamin D supplementation should be given as a part of routine antenatal care to all women to improve maternal and infant outcomes remains unclear. While there is some indication that vitamin D supplementation could reduce the risk of pre eclampsia and increase length and head circumference at birth, further rigorous randomized trials are required to confirm these effects. PMID- 27355805 TI - Exacerbation of demyelinating syndrome after exposure to wireless modem with public hotspot. AB - In August 2003, 48-year-old JS of Colorado, USA, a fitness therapist and sports nutritionist, contracted neuroinvasive West Nile virus which left her with disabilities due to spinal axonal damage.In August 2014, she suddenly developed symptoms very much like her acute West Nile infection 11 years ago, including focal seizures, ataxia, vertigo and headaches. Her blood count looked normal so there was no obvious infection. What struck her as odd was that when she left her apartment for any length of time, the symptoms stopped. She found out that a new type of wireless modem, enabled for both personal use and functioning as a public hotspot designed to reach up to 100 m, had been installed in the flat under hers.Her neighbor replaced the modem with a router without the hotspot feature. After that, the seizures stopped immediately, and the other symptoms faded gradually, after which she was fine and again could sleep well. Later, when another activated hotspot was installed in an adjacent flat, JS once again noticed symptoms.A possible association between electrohypersensitivity, myelin integrity and exposure to low-intensity radiofrequency electromagnetic fields (RF EMF) typical in the modern world has recently been proposed. Since the West Nile virus attacks both the nerve cells and the glial ones, one explanation to the above observed case effects is that the initial virus attack and the wireless modem's RF-EMF affect the nervous system through the very same, or similar, avenues, and maybe both via the oligodendrocytes. PMID- 27355804 TI - SNPs in NRXN1 and CHRNA5 are associated to smoking and regulation of GABAergic and glutamatergic pathways. AB - AIM: To identify genetic variants associated with greater tobacco consumption in a Mexican population. PATIENTS & METHODS: Daily smokers were classified as light smokers (LS; n = 742), heavy smokers (HS; n = 601) and nonsmokers (NS; n = 606). In the first stage, a genotyping microarray that included 347 SNPs in CHRNA2 CHRNA7/CHRNA10, CHRNB2-CHRNB4 and NRXN1 genes and 37 ancestry-informative markers was used to analyze 707 samples (187 HS, 328 LS and 192 NS). In the second stage, 14 SNPs from stage 1 were validated in the remaining samples (HS, LS and NS; n = 414 in each group) using real-time PCR. To predict the role of the associated SNPs, an in silico analysis was performed. RESULTS: Two SNPs in NRXN1 and two in CHRNA5 were associated with cigarette consumption, while rs10865246/C (NRXN1) was associated with high nicotine addiction. The in silico analysis revealed that rs1882296/T had a high level of homology with Hsa-miR-6740-5p, which encodes a putative miRNA that targets glutamate receptor subunits (GRIA2, GRID2) and GABA receptor subunits (GABRG1, GABRA4, GABRB2), while rs1882296/C had a high level of homology with Hsa-miR-6866-5p, which encodes a different miRNA that targets GRID2 and GABRB2. CONCLUSION: In a Mexican Mestizo population, greater consumption of cigarettes was influenced by polymorphisms in the NRXN1 and CHRNA5 genes. We proposed new hypotheses regarding the putative roles of miRNAs that influence the GABAergic and glutamatergic pathways in smoking addiction. PMID- 27355806 TI - Magnetic interactions in cubic-, hexagonal- and trigonal-barium iron oxide fluoride, BaFeO2F. AB - (57)Fe Mossbauer spectra have been recorded from the hexagonal (6H)- and trigonal (15R)- modifications of BaFeO2F and are compared with those previously recorded from the cubic form of BaFeO2F. The spectra, recorded over a temperature range from 15 to 650 K show that all of the iron in all the compounds is in the Fe(3+) state. Spectra from the 6H- and 15R-modifications were successfully fitted with components that were related to the Fe(1) and Fe(2) structural sites in the 6H variant and to the Fe(1), Fe(2) and Fe(3) structural sites in the 15R form. The magnetic ordering temperatures were determined as 597 +/- 3 K for 6H-BaFeO2F and 636 +/- 3 K for 15R-BaFeO2F. These values are surprisingly close to the value of 645 +/- 5 K determined for the cubic form. The magnetic interactions in the three forms are compared with a view to explaining this similarity of magnetic ordering temperature. PMID- 27355807 TI - Modulation of the vascular endothelium functioning by dietary components, the role of epigenetics. AB - Rather than being a passive barrier between circulating blood and smooth muscle cells and the underlying tissues, the endothelium is a fundamental functional component of the vasculature, and could be viewed as the largest human endocrine gland/organ, secreting multiple pro-/antiangiogenic factors, cytokines and low molecular-weight mediators controlling the vascular tone. The location of endothelium, at the interface between the circulation and the tissues, makes this epithelial layer particularly exposed to physical and chemical cues coming from the bloodstream. In response to such stimuli, the endothelium modulates its morphology and functions to maintain vascular homeostasis. Dietary components significantly affect the proper functioning of the endothelium. High-calories and high-fat western diets, in the long term, cause endothelial dysfunction, which is a major contributor to the development of the metabolic syndrome and its pathological consequences, including atherosclerosis, diabetes, and hypertension. On the contrary, plant-derived antioxidant molecules and polyphenols have been shown to exert beneficial effects on endothelial function. Extensive research in the last decade has clearly shown the close relationship between food intake, dietary habits, and gene expression, which is driven by the action of macro- and micronutrients on chromatin regulation. Nutrient-induced chromatin epigenetic modifications via DNA methylation and histone post-translational modifications, especially in the context of the western diet, significantly contribute to the dysregulation of endothelial functioning. Here, we review the current understanding on how dietary components (macronutrients, antioxidants), acting on epigenetic mechanisms, regulate endothelial physiology, and physiopathology. (c) 2016 BioFactors, 43(1):5-16, 2017. PMID- 27355808 TI - Development of a tethered personal health record framework for early end-of-life discussions. AB - OBJECTIVES: End-of-life planning, known as advance care planning (ACP), is associated with numerous positive outcomes, such as improved patient satisfaction with care and improved patient quality of life in terminal illness. However, patient-provider ACP conversations are rarely performed or documented due to a number of barriers, including time required, perceived lack of skill, and a limited number of resources. Use of tethered personal health records (PHRs) may help streamline ACP conversations and documentations for outpatient workflows. Our objective was to develop an ACP-PHR framework that would be for use in a primary care, outpatient setting. STUDY DESIGN: Qualitative content analysis of focus groups and cognitive interviews (participatory design). METHODS: A novel PHR-ACP tool was developed and tested using data and feedback collected from 4 patient focus groups (n = 13), 1 provider focus group (n = 4), and cognitive interviews (n = 22). RESULTS: Patient focus groups helped develop a focused, 4 question PHR communication tool. Cognitive interviews revealed that, while patients felt framework content and workflow were generally intuitive, minor changes to content and workflow would optimize the framework. CONCLUSIONS: A focused framework for electronic ACP communication using a patient portal tethered to the PHR was developed. This framework may provide an efficient way to have ACP conversations in busy outpatient settings. PMID- 27355809 TI - Variations in patient response to tiered physician networks. AB - OBJECTIVES: Prior studies found that tiered provider networks channel patients to preferred providers in certain contexts. This paper evaluates whether the effects of tiered physician networks vary for different types of patients. STUDY DESIGN: Cross-sectional analysis of fiscal year 2009 to 2010 administrative enrollment and claims data on nonelderly beneficiaries in Massachusetts Group Insurance Commission health plans. METHODS: Main outcome measures are physician market share among new patients and the percent of physician's patients who switch away. We utilized estimated fixed effects linear regression models that were stratified by patient characteristics. RESULTS: Physicians with the worst tier rankings had lower market share among new patients who are older and sicker, or male, representing losses in market share of 10% and 15%, respectively, than other tiered physicians. A poor tier ranking did not affect physician market share of new patients who are female or younger. There was no effect of a physician's tier ranking on the proportion of patients who switch to other doctors among any groups of patients. CONCLUSIONS: Loyalty to their own physicians is pervasive across groups of patients. Physicians with poor tier rankings lost market share among new patients who are older and sicker, and among new male patients. Together, these findings suggest that tiered network designs have the potential for the greatest impact on value in healthcare over time, as more patients seek new relationships with physicians. PMID- 27355810 TI - Primary care appointment availability and nonphysician providers one year after Medicaid expansion. AB - OBJECTIVES: With insurance enrollment greater than expected under the Affordable Care Act, uncertainty about the availability and timeliness of healthcare services for newly insured individuals has increased. We examined primary care appointment availability and wait times for new Medicaid and privately insured patients before and after Medicaid expansion in Michigan. STUDY DESIGN: Simulated patient ("secret shopper") study. METHODS: Extended follow-up of a previously reported simulated patient ("secret shopper") study assessing accessibility of routine new patient appointments in a stratified proportionate random sample of Michigan primary care practices before versus 4, 8, and 12 months after Medicaid expansion. RESULTS: During the study period, approximately 600,000 adults enrolled in Michigan's Medicaid expansion program, representing 57% of the previously uninsured nonelderly adult population. One year after expansion, we found that appointment availability remained increased by 6 percentage points for new Medicaid patients (95% CI, 1.6-11.1) and decreased by 2 percentage points for new privately insured patients (95% CI, -0.5 to -3.8). Over the same period, the proportion of appointments scheduled with nonphysician providers (nurse practitioners or physician assistants) increased from 8% to 21% of Medicaid appointments (95% CI, 5.6-20.2) and from 11% to 19% of private-insurance appointments (95% CI, 1.3-14.1). Median wait times remained stable for new Medicaid patients and increased slightly for new privately insured patients, both remaining within 2 weeks. CONCLUSIONS: During the first year following Medicaid expansion in Michigan, appointment availability for new Medicaid patients increased, a greater proportion of appointments could be obtained with nonphysician providers, and wait times remained within 2 weeks. PMID- 27355811 TI - Impact of type 2 diabetes medication cost sharing on patient outcomes and health plan costs. AB - OBJECTIVES: To study the association between cost sharing for diabetes medications, adherence, hospitalization rates, and healthcare costs, with relationship to patient risk. STUDY DESIGN: A retrospective claims analysis of data from 35 large, private, self-insured employers (2004 to 2012). METHODS: We examined outcomes for 92,410 patients aged 18 to 64 years with a type 2 diabetes (T2D) diagnosis who filled at least 1 T2D prescription. First, we examined the relationship between adherence, measured as the proportion of days covered, and cost sharing, measured as the out-of-pocket cost to purchase a pre-specified bundle of T2D prescriptions. We then examined the association between adherence and hospital days. Simulations showed the effect of increased cost sharing on adherence and inpatient utilization. RESULTS: A $10 increase in out-of-pocket cost was associated with a 1.9% reduction in adherence (P < .01). In turn, a 10% reduction in adherence was associated with a 15% increase in per-patient hospital days (0.17 days; P < .01). For the average plan, switching from low to high cost sharing reduced per-patient medication costs by $242 and increased per-patient hospitalization costs by $342, for a net increase of $100 in plan costs. Increases in per-patient costs were greater for high-risk patients, such as those with heart failure ($1328). CONCLUSIONS: Increased cost sharing for T2D medication was associated with reductions in pharmacy costs, but higher total costs for patients with T2D. This problem is particularly acute for patients with 1 or more cardiovascular comorbidities. The results suggest that increased diabetes cost sharing may hamper efforts to lower the total cost of diabetes care. PMID- 27355812 TI - Risk contracting and operational capabilities in large medical groups during national healthcare reform. AB - OBJECTIVES: Little is known about the scope of alternative payment models outside of Medicare. This study measures the full complement of public and private payment arrangements in large, multi-specialty group practices as a barometer of payment reform among advanced organizations. STUDY DESIGN AND METHODS: We collected information from 33 large, multi-specialty group practices about the proportion of their total revenue in 7 payment models, physician compensation strategies, and the implementation of selected performance management initiatives. We grouped respondents into 3 categories based on the proportion of their revenue in risk arrangements: risk-based (45%-100%), mixed (10%-35%), and fee-for-service (FFS) (0%-10%). We analyzed changes in contracting and operating characteristics between 2011 and 2013. RESULTS: In 2013, 68% of groups' total patient revenue was from FFS payments and 32% was from risk arrangements (unweighted average). Risk-based groups had 26% FFS revenue, whereas mixed payment and FFS groups had 75% and 98%, respectively. Between 2011 and 2013, 9 groups increased risk contract revenue by about 15 percentage points and 22 reported few changes. Risk-based groups reported more advanced implementation of performance management strategies and were more likely to have physician financial incentives for quality and patient experience. CONCLUSIONS: The groups in this study are well positioned to manage risk-based contracts successfully, but less than one-third receive a majority of their revenue from risk arrangements. The experience of these relatively advanced groups suggests that expanding risk-based arrangements across the US health system will likely be slower and more challenging than many people assume. PMID- 27355813 TI - The value of decreasing health cost volatility. PMID- 27355814 TI - Digital Planning Software Fails to Reflect Stem Torsion on Plain Radiographs after Total Hip Arthroplasty. AB - PURPOSE: The purpose of this study was to evaluate the validity of commercially available planning software on plain radiographs after THA compared to CT scans as the gold standard. PATIENTS AND METHODS: In a prospective clinical study, anteroposterior (AP) radiographs and three-dimensional CT scans (3D-CT) were obtained for 121 patients, who underwent minimally invasive, cementless THA with a straight tapered stem, in a lateral decubitus position. For measuring SV, we used digital planning software (TraumaCad 2.0, BrainLAB Feldkirchen, Germany). Two independent raters repeated the analysis after a six-week interval. Radiological measurements were compared with 3D-CT measurements by an independent, blinded external institute. This investigation was approved by the local ethics commission (no. 10 -121- 0263) and is a secondary analysis of a larger project (DRKS00 000 739, German Clinical Trials Register May-02 - 2011). RESULTS: The radiograph measurements showed very high intra- and interrater agreement. The intra-class correlation (ICC) of the intrarater agreement was 0.97 for rater 1 and 0.98 for rater 2. The intrarater reliability was 0.99 using the mean values of both rater measurements. The mean difference between the average radiograph measurement and the 3D-CT-based measurement was 0.41 degrees (SD 11.24 degrees ) (range: -33.85 degrees -22.50 degrees ; 95 % limits of agreement: -21.63 - 22.45), but there was no correlation found between both methods. CONCLUSION: Measuring stem version with the help of commercially available digital planning software on plain radiographs after THA has high intra- and interrater reliability but clinically inacceptable validity and reliability when compared to 3D-CT scans. KEY POINTS: * Measuring stem torsion after THA on plain radiographs with digital planning software is not valid. Citation Format: * Worlicek M, Weber M, Zeman F et al. Digital Planning Software Fails to Reflect Stem Torsion on Plain Radiographs after Total Hip Arthroplasty. Fortschr Rontgenstr 2016; 188: 763 - 767. PMID- 27355815 TI - Prevalence and predictors of subjective memory complaints in adult male carriers of the FMR1 premutation. AB - OBJECTIVE: To examine the prevalence and predictors of subjective memory complaints among a cohort of male FMR1 premutation (PM) carriers with and without fragile X-associated tremor ataxia syndrome (FXTAS). METHOD: Twenty-two PM males (ages 26-80, 7 with FXTAS) and 24 matched controls with normal FMR1 alleles (ages 26-77) completed cross-sectional assessments of subjective memory complaints (memory complaints questionnaire, MAC-Q), objective memory function (Logical Memory subtest from the Wechsler Memory Scale, third edition), and psychiatric symptoms (Depression, Anxiety, and Stress Scales; the Structured Clinical Interview for DSM-IV-TR Axis I Disorders). RESULTS: Although a greater proportion of PM males (36%) endorsed subjective memory complaints compared to controls (21%), formal statistical comparisons failed to reach significance. Multiple linear regression analyses revealed that subjective memory complaints were not associated with objective memory performance, but rather were predicted by elevated psychiatric symptoms. The relationship between psychiatric symptoms and subjective complaints found in the PM group was not statistically different to that found in the control group. There were no significant relationships between FMR1 molecular measures (CGG repeat length, FMR1 mRNA level) and measures of subjective memory complaints, objective memory performance, or psychiatric symptoms. CONCLUSIONS: In keeping with findings from the general population, this study suggests that subjective ratings of memory performance in PM males are associated with underlying psychological factors rather than cross-sectional objective memory function. However, future longitudinal studies are required to determine whether subjective memory complaints may predict changes in objective memory function over time. PMID- 27355816 TI - Oral Immunotherapy for Food Allergies. AB - Oral immunotherapy (OIT) is a promising investigational therapy for food allergy. Clinical trials in peanut, milk, egg, and wheat allergy provide evidence that OIT can effectively desensitize a majority of individuals to a food allergen. While a portion of subjects demonstrate sustained unresponsiveness, the majority regain sensitivity with allergen avoidance. The safety and tolerability of OIT continue to limit its use in some patients. Virtually all studies report adverse reactions that are more frequent during dose escalation but may also occur during maintenance therapy. Recent studies have identified adjunctive therapies (such as omalizumab) which may mitigate adverse effects. There is a paucity of data on the long-term safety and efficacy of OIT. Further study is required before OIT is ready for routine clinical practice. This review is intended to provide the reader with an up-to-date understanding of OIT, including its mechanisms, efficacy, safety profile, and potential utility in clinical practice. PMID- 27355817 TI - How Big of a Problem is Analytic Error in Secondary Analyses of Survey Data? AB - Secondary analyses of survey data collected from large probability samples of persons or establishments further scientific progress in many fields. The complex design features of these samples improve data collection efficiency, but also require analysts to account for these features when conducting analysis. Unfortunately, many secondary analysts from fields outside of statistics, biostatistics, and survey methodology do not have adequate training in this area, and as a result may apply incorrect statistical methods when analyzing these survey data sets. This in turn could lead to the publication of incorrect inferences based on the survey data that effectively negate the resources dedicated to these surveys. In this article, we build on the results of a preliminary meta-analysis of 100 peer-reviewed journal articles presenting analyses of data from a variety of national health surveys, which suggested that analytic errors may be extremely prevalent in these types of investigations. We first perform a meta-analysis of a stratified random sample of 145 additional research products analyzing survey data from the Scientists and Engineers Statistical Data System (SESTAT), which describes features of the U.S. Science and Engineering workforce, and examine trends in the prevalence of analytic error across the decades used to stratify the sample. We once again find that analytic errors appear to be quite prevalent in these studies. Next, we present several example analyses of real SESTAT data, and demonstrate that a failure to perform these analyses correctly can result in substantially biased estimates with standard errors that do not adequately reflect complex sample design features. Collectively, the results of this investigation suggest that reviewers of this type of research need to pay much closer attention to the analytic methods employed by researchers attempting to publish or present secondary analyses of survey data. PMID- 27355818 TI - Gender differences in posttraumatic stress symptoms and social support in a sample of HIV-positive individuals. AB - The aim of the authors of the present study was to investigate gender differences in the levels of posttraumatic stress symptoms (PTSS) and social support in a Polish sample of HIV+ men (n = 613) and women (n = 230). This was an anonymous cross-sectional study, and participation was voluntary. The research questionnaires were distributed in paper form among patients of Warsaw's Hospital for Infectious Diseases from January to October 2015. The level of PTSS was assessed using the PTSD Factorial Version Inventory. Social support was assessed using the Berlin Social Support Scales. HIV+ women scored higher on all PTSS dimensions compared to HIV+ men. HIV+ women were characterized by a higher need for support and more support actually received compared to HIV+ men. We observed a positive association between HIV infection duration and AIDS phase and the global trauma score only among HIV+ men. The moderation analysis also revealed a positive relationship between actual received support and the global trauma score among HIV+ women only. Increased clinician awareness is needed about the role of PTSS and social support among people living with HIV, especially taking gender differences into account. PMID- 27355819 TI - 1,2,4,5-Tetramethoxybenzene Suppresses House Dust Mite-Induced Allergic Inflammation in BALB/c Mice. AB - BACKGROUND: Atopic dermatitis (AD) is the most common allergic inflammatory skin disease. The activation of innate immunity by house dust mite (Dermatophagoides farinae extract, DFE) allergen plays an important role in the pathogenesis of AD. We previously showed the inhibitory effect of an extract of Amomum xanthioides on allergic diseases, and isolated 1,2,4,5-tetramethoxybenzene (TMB) as a major active component. In this study, we investigated whether TMB relieves DFE-induced allergic inflammation symptoms. METHODS: We established a DFE-induced allergic inflammation model in BALB/c mice by repeated skin exposure to DFE. To define the underlying mechanisms of action, we used a tumor necrosis factor-alpha and interferon-x03B3;-activated human keratinocytes (HaCaT cell line) and mouse keratinocytes (3PC cell line) cell line model. RESULTS: Oral administration of TMB suppressed allergic inflammation symptoms, such as histopathological analysis and ear thickness, in addition to serum IgE, DFE-specific IgE and IgG2a levels. TMB decreased the serum histamine levels and tissue infiltration of inflammatory cells, including mast cells and eosinophils. TMB also inhibited CD4+IFN-x03B3;+, CD4+IL-4+, and CD4+IL-17A+ lymphocyte expansion in the draining lymph nodes and expression of the Th2 cytokines in the ear tissue. TMB significantly inhibited the expression of cytokines and chemokines by the downregulation of the mitogen activated protein kinases and nuclear factor of activated cytoplasmic T cells in HaCaT cells. CONCLUSIONS: TMB improved DFE-induced allergic inflammation by suppressing the production of proinflammatory cytokines and chemokines. Our results suggest that TMB might be a potential therapeutic agent for AD. PMID- 27355820 TI - Statement of the Declaration of Istanbul Custodian Group Regarding Payments to Families of Deceased Organ Donors. AB - Governmental and private programs that pay next of kin who give permission for the removal of their deceased relative's organs for transplantation exist in a number of countries. Such payments, which may be given to the relatives or paid directly for funeral expenses or hospital bills unrelated to being a donor, aim to increase the rate of donation. The Declaration of Istanbul Custodian Group-in alignment with the World Health Organization Guiding Principles and the Council of Europe Convention Against Trafficking in Human Organs-has adopted a new policy statement opposing such practices. Payment programs are unwise because they produce a lower rate of donations than in countries with voluntary, unpaid programs; associate deceased donation with being poor and marginal in society; undermine public trust in the determination of death; and raise doubts about fair allocation of organs. Most important, allowing families to receive money for donation from a deceased person, who is at no risk of harm, will make it impossible to sustain prohibitions on paying living donors, who are at risk. Payment programs are also unethical. Tying coverage for funeral expenses or healthcare costs to a family allowing organs to be procured is exploitative, not "charitable." Using payment to overcome reluctance to donate based on cultural or religious beliefs especially offends principles of liberty and dignity. Finally, while it is appropriate to make donation "financially neutral"-by reimbursing the added medical costs of evaluating and maintaining a patient as a potential donor such reimbursement may never be conditioned on a family agreeing to donate. PMID- 27355822 TI - Admission Plasma Troponin I Is Associated With Mortality in Pediatric Intensive Care. AB - OBJECTIVES: Assessment of whether admission plasma troponin I level is associated with mortality or requirement for vasoactive drugs in pediatric intensive care. DESIGN: Retrospective cohort study. SETTING: Single centre, tertiary referral general PICU, without a cardiac surgical program. PATIENTS: Three hundred and nineteen patients 0-18 years old in two cohorts. Cohort 1 was admitted between January 2009 and September 2012 and the cohort 2 between April 2014 and April 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma troponin I was measured in patients in cohort 1 only if the attending physician ordered the test due to clinical concern regarding myocardial injury. The second cohort had plasma troponin I routinely measured at admission. The primary outcome was death during PICU admission, and the secondary outcome was maximum inotrope requirement during PICU stay, measured by Vasoactive Inotrope Score. Plasma troponin I was a discriminator for mortality in both cohorts (area under the receiver-operating characteristic curve of 0.73 and 0.86 in cohorts 1 and 2, respectively). In an adjusted analysis using Cox regression, accounting for Pediatric Index of Mortality 2 risk of mortality and age, elevated plasma troponin I was significantly associated with death in both cohorts (hazard ratio, 4.99; p = 0.033; hazard ratio, 10.5; p = 0.026 in cohorts 1 and 2, respectively). Elevated plasma troponin I was only associated with increased Vasoactive Inotrope Score following multivariate analysis in the cohort 2. CONCLUSIONS: Detectable plasma troponin I at admission to PICU is independently associated with death. The utility of troponin I as a stratification biomarker requires further evaluation. PMID- 27355821 TI - Characterizing Blood Metabolomics Profiles Associated with Self-Reported Food Intakes in Female Twins. AB - Using dietary biomarkers in nutritional epidemiological studies may better capture exposure and improve the level at which diet-disease associations can be established and explored. Here, we aimed to identify and evaluate reproducibility of novel biomarkers of reported habitual food intake using targeted and non targeted metabolomic blood profiling in a large twin cohort. Reported intakes of 71 food groups, determined by FFQ, were assessed against 601 fasting blood metabolites in over 3500 adult female twins from the TwinsUK cohort. For each metabolite, linear regression analysis was undertaken in the discovery group (excluding MZ twin pairs discordant [>=1 SD apart] for food group intake) with each food group as a predictor adjusting for age, batch effects, BMI, family relatedness and multiple testing (1.17x10-6 = 0.05/[71 food groups x 601 detected metabolites]). Significant results were then replicated (non-targeted: P<0.05; targeted: same direction) in the MZ discordant twin group and results from both analyses meta-analyzed. We identified and replicated 180 significant associations with 39 food groups (P<1.17x10-6), overall consisting of 106 different metabolites (74 known and 32 unknown), including 73 novel associations. In particular we identified trans-4-hydroxyproline as a potential marker of red meat intake (0.075[0.009]; P = 1.08x10-17), ergothioneine as a marker of mushroom consumption (0.181[0.019]; P = 5.93x10-22), and three potential markers of fruit consumption (top association: apple and pears): including metabolites derived from gut bacterial transformation of phenolic compounds, 3-phenylpropionate (0.024[0.004]; P = 1.24x10-8) and indolepropionate (0.026[0.004]; P = 2.39x10-9), and threitol (0.033[0.003]; P = 1.69x10-21). With the largest nutritional metabolomics dataset to date, we have identified 73 novel candidate biomarkers of food intake for potential use in nutritional epidemiological studies. We compiled our findings into the DietMetab database (http://www.twinsuk.ac.uk/dietmetab data/), an online tool to investigate our top associations. PMID- 27355824 TI - Factors Associated With Mortality in Neonates Requiring Extracorporeal Membrane Oxygenation for Cardiac Indications: Analysis of the Extracorporeal Life Support Organization Registry Data. AB - OBJECTIVES: Survival among neonates supported with extracorporeal membrane oxygenation for cardiac indications is 39%. Previous single-center studies have identified factors associated with mortality, but a comprehensive multivariate analysis is not available for this population. Understanding factors associated with mortality may help design treatment strategies, determine optimal timing for cannulation, and inform patient selection. This study identifies factors associated with mortality in neonates supported with extracorporeal membrane oxygenation for cardiac indications. DESIGN: Retrospective cohort study. SETTING: Two hundred and thirty U.S. and international centers reporting extracorporeal membrane oxygenation data to the Extracorporeal Life Support Organization. SUBJECTS: Four thousand and four seventy one neonates with congenital and acquired cardiac disease supported with extracorporeal membrane oxygenation for cardiac indications during 2001-2011. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The primary outcome measure was mortality prior to hospital discharge. Overall hospital mortality was 59%. Demographic and preextracorporeal membrane oxygenation factors associated with mortality were evaluated in a multivariable model. Factors associated with death prior to hospital discharge included lower body weight, earlier era, single ventricle physiology, lower preextracorporeal membrane oxygenation arterial pH, and longer time from intubation to extracorporeal membrane oxygenation cannulation. Lower pH was associated with increased mortality regardless of cardiac diagnosis and surgical complexity. The majority of survivors separated from extracorporeal membrane oxygenation less than 8 days after extracorporeal membrane oxygenation deployment. CONCLUSIONS: Mortality for neonates supported with extracorporeal membrane oxygenation for cardiac indications is high. Severity of preextracorporeal membrane oxygenation acidosis was independently associated with increased risk of mortality. Earlier initiation of extracorporeal membrane oxygenation may reduce the degree and duration of acidosis and may improve survival. Further studies are needed to determine optimal timing of cannulation in this population. PMID- 27355823 TI - Comparison of Intraoperative Aminophylline Versus Furosemide in Treatment of Oliguria During Pediatric Cardiac Surgery. AB - OBJECTIVES: To determine if intraoperative aminophylline was superior to furosemide to prevent or attenuate postoperative cardiac surgery-associated acute kidney injury. DESIGN: Single-center, historical control, retrospective cohort study. SETTING: PICU, university-affiliated children's hospital. PATIENTS: Children with congenital heart disease in PICU who received furosemide or aminophylline to treat intraoperative oliguria. INTERVENTIONS: Intraoperative oliguria was treated either with furosemide (September 2007 to February 2012) or with aminophylline (February 2012 to June 2013). The postoperative 48 hours renal outcomes of the aminophylline group were compared with the furosemide group. The primary outcomes were acute kidney injury and renal replacement therapy use at 48 hours postoperatively. Surgical complexity was accounted for by the use of Risk Adjustment for Congenital Heart Surgery-1 score. MEASUREMENTS AND MAIN RESULTS: The study involves 69 months of observation. There were 200 cases younger than 21 years old reviewed for this study. Eighty-five cases (42.5%) developed acute kidney injury. The aminophylline group patients produced significantly more urine (mL/kg/hr) during the first 8 hours postoperatively than furosemide patients (5.1 vs 3.4 mL/kg/hr; p = 0.01). The urine output at 48 hours postoperatively was similar between the two groups. There was no difference in acute kidney injury incidence at 48 hours between the aminophylline and furosemide groups (38% vs 47%, respectively; p = 0.29). Fewer aminophylline group subjects required renal replacement therapy compared to the furosemide group subjects (n = 1 vs 7, respectively; p = 0.03). In the multi-variant predictive model, intraoperative aminophylline infusion was noted as a negative predictive factor for renal replacement therapy, but not for cardiac surgery-associated acute kidney injury. CONCLUSION: The intraoperative use of aminophylline was more effective than furosemide in reversal of oliguria in the early postoperative period. There were less renal replacement therapy-requiring acute kidney injury in children in the aminophylline group. Future prospective studies of intraoperative aminophylline to prevent cardiac surgery-associated acute kidney injury may be warranted. PMID- 27355825 TI - A Pediatric Sedation Protocol for Mechanically Ventilated Patients Requires Sustenance Beyond Implementation. AB - OBJECTIVES: To reevaluate the effect of a nursing-driven sedation protocol for mechanically ventilated patients on analgesic and sedative medication dosing durations. We hypothesized that lack of continued quality improvement efforts results in increased sedation exposure, as well as mechanical ventilation days, and ICU length of stay. DESIGN: Quasi-experimental, uncontrolled before-after study. SETTING: Forty-five-bed tertiary care, medical-surgical-cardiac PICU in a metropolitan university-affiliated children's hospital. PATIENTS: Children requiring mechanical ventilation longer than 48 hours not meeting exclusion criteria. INTERVENTIONS: During both the intervention and postintervention periods, analgesia and sedation were managed by nurses following an algorithm based sedation protocol with a targeted comfort score. MEASUREMENT AND MAIN RESULTS: The intervention cohort includes patients admitted during a 12-month period following initial protocol implementation in 2008-2009 (n = 166). The postintervention cohort includes patients meeting identical inclusion and exclusion criteria admitted during a 12-month period in 2012-2013 (n = 93). Median duration of total sedation days (IV plus enteral) was 5 days for the intervention period and 10 days for the postintervention period (p < 0.0001). The postintervention cohort received longer duration of mechanical ventilation (6 vs 5 d; p = 0.0026) and ICU length of stay (10 vs 8.5 d; p = 0.0543). After adjusting for illness severity and cardiac and surgical status, Cox proportional hazards regression analysis demonstrated that at any point in time, patients in the postintervention group were 58% more likely to be receiving sedation (hazard ratio, 1.58; p < 0.001) and 34% more likely to remain in the ICU (hazard ratio, 1.34; p = 0.019). CONCLUSIONS: Sedation quality improvement measures related to the use of opiate infusions, total days of sedation exposure, PICU length of stay, and mechanical ventilation days all deteriorated following initial successful implementation of a PICU sedation protocol. Implementation of a protocol alone may not lead to sustained quality improvement without routine monitoring and ongoing education to ensure effectiveness. PMID- 27355826 TI - Storage and Drainage Characteristics of a Highly Heterogeneous Karst Aquifer in Houzhai Basin. AB - The characteristics of karst aquifers are difficult to be determined due to their heterogeneous physical properties and lack of hydrogeological information. In this case study, we applied two methods for a comparative analysis of storage and drainage characteristics in upstream, midstream, and downstream of Houzhai cave stream basin. In the first method, Minimum Smoothed Method (MSM) is used to determine the proportion of baseflow to the total flow (Baseflow Index, BFI). In the second method, a bicarbonate-base two-end member mixing model is used to quantify the slow flow component and fast flow component. For both methods, slow flow and quick flow are quantified at three sampling sites, which provide useful information for the analysis of storage and drainage characteristics. The results from flow separation method and hydrogeochemical analysis show a consistently increasing trend of the proportion of slow flow to total flow from the upstream to downstream which indicates that the voids of highly conductive conduits and well-connected fissures decrease along the flow paths in the Houzhai cave stream basin in southwest China. The upstream areas have a low proportion of baseflow which indicates a high drainage capacity due to high permeable conduits and well connected fissures. The downstream areas, on the contrary, have a high proportion of baseflow which indicates a high storage capacity and slow infiltration due to the predominant presence of matrix and poorly-connected fissures. These numerical methods provide alternative ways to investigate the storage and drainage characteristics of karst aquifers where direct measurement are not available. PMID- 27355828 TI - Chorioamnionitis and Five-Year Neurodevelopmental Outcome in Preterm Infants. AB - BACKGROUND: Chorioamnionitis, a risk factor for preterm delivery, has been suggested to be associated with suboptimal neurological development in premature infants. OBJECTIVE: To evaluate the association between chorioamnionitis and neurodevelopment in preterm infants at 5 years of age. Methods Very low birth weight and very low gestational age infants (n = 197) were recruited. Placental samples (n = 117) were evaluated for histological chorioamnionitis. Fetal histological chorioamnionitis was analyzed as a subgroup. The diagnosis of clinical chorioamnionitis was derived from medical records. Neurodevelopmental impairments were evaluated at 2 years of age, and cognitive development (n = 188) and neuropsychological performance (n = 193) were evaluated at 5 years of age. RESULTS: There were no associations between histological or clinical chorioamnionitis and neurodevelopmental impairments at 2 years of age. Clinical chorioamnionitis and fetal histological chorioamnionitis were not associated with cognitive development or neuropsychological performance, but histological chorioamnionitis was associated with poorer cognitive outcome (regression coefficient = -7.22, 95% CI: -14.31 to -0.13) and weaker memory and learning functions (regression coefficient = -1.29, 95% CI: -2.40 to -0.18) at 5 years of age. CONCLUSION: Our study findings do not support clinical chorioamnionitis having a major independent role in the pathogenesis of neurodevelopmental problems in very preterm infants. Histological chorioamnionitis was associated with slightly less optimal performance at 5 years of age, but further studies are needed to verify the clinical significance of these findings. PMID- 27355827 TI - A Conserved MicroRNA Regulatory Circuit Is Differentially Controlled during Limb/Appendage Regeneration. AB - BACKGROUND: Although regenerative capacity is evident throughout the animal kingdom, it is not equally distributed throughout evolution. For instance, complex limb/appendage regeneration is muted in mammals but enhanced in amphibians and teleosts. The defining characteristic of limb/appendage regenerative systems is the formation of a dedifferentiated tissue, termed blastema, which serves as the progenitor reservoir for regenerating tissues. In order to identify a genetic signature that accompanies blastema formation, we employ next-generation sequencing to identify shared, differentially regulated mRNAs and noncoding RNAs in three different, highly regenerative animal systems: zebrafish caudal fins, bichir pectoral fins and axolotl forelimbs. RESULTS: These studies identified a core group of 5 microRNAs (miRNAs) that were commonly upregulated and 5 miRNAs that were commonly downregulated, as well as 4 novel tRNAs fragments with sequences conserved with humans. To understand the potential function of these miRNAs, we built a network of 1,550 commonly differentially expressed mRNAs that had functional relationships to 11 orthologous blastema associated genes. As miR-21 was the most highly upregulated and most highly expressed miRNA in all three models, we validated the expression of known target genes, including the tumor suppressor, pdcd4, and TGFbeta receptor subunit, tgfbr2 and novel putative target genes such as the anti-apoptotic factor, bcl2l13, Choline kinase alpha, chka and the regulator of G-protein signaling, rgs5. CONCLUSIONS: Our extensive analysis of RNA-seq transcriptome profiling studies in three regenerative animal models, that diverged in evolution ~420 million years ago, reveals a common miRNA-regulated genetic network of blastema genes. These comparative studies extend our current understanding of limb/appendage regeneration by identifying previously unassociated blastema genes and the extensive regulation by miRNAs, which could serve as a foundation for future functional studies to examine the process of natural cellular reprogramming in an injury context. PMID- 27355829 TI - Renewability is not Enough: Recent Advances in the Sustainable Synthesis of Biomass-Derived Monomers and Polymers. AB - Taking advantage of the structural diversity of different biomass resources, recent efforts were directed towards the synthesis of renewable monomers and polymers, either for the substitution of petroleum-based resources or for the design of novel polymers. Not only the use of biomass, but also the development of sustainable chemical approaches is a crucial aspect for the production of sustainable materials. This review discusses the recent examples of chemical modifications and polymerizations of abundant biomass resources with a clear focus on the sustainability of the described processes. Topics such as synthetic methodology, catalysis, and development of new solvent systems or greener alternative reagents are addressed. The chemistry of vegetable oil derivatives, terpenes, lignin, carbohydrates, and sugar-based platform chemicals was selected to highlight the trends in the active field of a sustainable use of renewable resources. PMID- 27355831 TI - Rare-earth-free white emitting Ba2TiP2O9 phosphor: revealing its crystal structure and photoluminescence properties. AB - A high intensity bluish-white emitting Ba2TiP2O9 phosphor was synthesized by a conventional solid-state reaction method and the precise crystal structure was investigated for the first time by Rietveld refinement analysis. Ba2TiP2O9 has a monoclinic crystal structure with a space group C2/c (no. 15), which is built out of PO4 tetrahedra and TiO5 pyramidal polyhedra connected to form a chain structure along the c-axis. The emission of Ba2TiP2O9 is due to a charge transfer transition between Ti(4+)-O(2-) in the pyramidal TiO5. The obtained Ba2TiP2O9 was excited efficiently by UV and VUV and displayed a bright bluish-white luminescence. PMID- 27355830 TI - Postural Stability of Patients with Schizophrenia during Challenging Sensory Conditions: Implication of Sensory Integration for Postural Control. AB - Postural dysfunctions are prevalent in patients with schizophrenia and affect their daily life and ability to work. In addition, sensory functions and sensory integration that are crucial for postural control are also compromised. This study intended to examine how patients with schizophrenia coordinate multiple sensory systems to maintain postural stability in dynamic sensory conditions. Twenty-nine patients with schizophrenia and 32 control subjects were recruited. Postural stability of the participants was examined in six sensory conditions of different level of congruency of multiple sensory information, which was based on combinations of correct, removed, or conflicting sensory inputs from visual, somatosensory, and vestibular systems. The excursion of the center of pressure was measured by posturography. Equilibrium scores were derived to indicate the range of anterior-posterior (AP) postural sway, and sensory ratios were calculated to explore ability to use sensory information to maintain balance. The overall AP postural sway was significantly larger for patients with schizophrenia compared to the controls [patients (69.62+/-8.99); controls (76.53+/-7.47); t1,59 = -3.28, p<0.001]. The results of mixed-model ANOVAs showed a significant interaction between the group and sensory conditions [F5,295 = 5.55, p<0.001]. Further analysis indicated that AP postural sway was significantly larger for patients compared to the controls in conditions containing unreliable somatosensory information either with visual deprivation or with conflicting visual information. Sensory ratios were not significantly different between groups, although small and non-significant difference in inefficiency to utilize vestibular information was also noted. No significant correlations were found between postural stability and clinical characteristics. To sum up, patients with schizophrenia showed increased postural sway and a higher rate of falls during challenging sensory conditions, which was independent of clinical characteristics. Patients further demonstrated similar pattern and level of utilizing sensory information to maintain balance compared to the controls. PMID- 27355832 TI - Drug List as a Cognitive Support to Provide Detailed Information on a Patient's Drug Use: A Comparison of Two Methods Within the Assessment of Drug Misuse and Dependence. AB - BACKGROUND: It is important to identify the type of drugs a patient has used, especially when polydrug misuse has increased and new drugs and patterns of misuse are quickly spread. OBJECTIVES: In order to acquire sufficient information about drug use, an effective and simple form of mapping is needed. METHODS: Persons actualized for Opioid Substitution Treatment (n = 135) were interviewed about their drug-history in a two-stage model. First, they were asked to write down the drugs misused, and dot those injected with a felt pen. Second, they were asked to do the same on a drug list provided as a cognitive support. For a subsample of 50 persons, the drug list included four fictive drugs to evaluate possible over-reporting. RESULTS: The use of a drug list did not take longer than the traditional way of using open questions, i.e. about 5-8 minutes. Using a drug list gave a cognitive support resulting in a much higher proportion/number of reported drugs. The majority, 97%, used more than one drug. None of the patients who were given the drug list that included fictive drug names reported having used any of them. The respondents reported 43 additional substances to the 125 given on the list which improve our knowledge of the drug scene. CONCLUSIONS/IMPORTANCE: Using a drug-list was superior to open questions; it does not take more time and provides additional, clinically relevant information than open questions. Using a drug-list also gives improved knowledge of new drugs entering the local drug scene. PMID- 27355833 TI - Antibacterial and Solubility Optimization of Thiomuracin A. AB - Synthetic studies of the antimicrobial secondary metabolite thiomuracin A (1) provided access to analogues in the Northern region (C2-C10). Selective hydrolysis of the C10 amide of lead compound 2 and subsequent derivatization led to novel carbon- and nitrogen-linked analogues (e.g., 3) which improved antibacterial potency across a panel of Gram-positive organisms. In addition, congeners with improved physicochemical properties were identified which proved efficacious in murine sepsis and hamster C. difficile models of disease. Optimal efficacy in the hamster model of C. difficile was achieved with compounds that possessed both potent antibacterial activity and high aqueous solubility. PMID- 27355835 TI - The influence of image content on oculomotor plasticity. AB - When we observe a scene, we shift our gaze to different points of interest via saccadic eye movements. Saccades provide high resolution views of objects and are essential for vision. The successful view of an interesting target might constitute a rewarding experience to the oculomotor system. We measured the influence of image content on learning efficiency in saccade control. We compared meaningful pictures to luminance and spatial frequency-matched random noise images in a saccadic adaptation paradigm. In this paradigm a shift of the target during the saccades results in a gradual increase of saccade amplitude. Stimuli were masked at different times after saccade onset. For immediate masking of the stimuli, as well as for their permanent visibility, saccadic adaptation was similar for both types of targets. However, when stimuli were masked 200 ms after saccade onset, adaptation of saccades directed toward the meaningful target stimuli was significantly greater than that of saccades directed toward noise targets. Thus, the percept of a meaningful image at the saccade landing position facilitates learning of the appropriate parameters for saccadic motor control when time constraints exist. We conclude that oculomotor learning, which is traditionally considered a low-level and highly automatized process, is modulated by the visual content of the image. PMID- 27355834 TI - Specific Deficit in Implicit Motor Sequence Learning following Spinal Cord Injury. AB - BACKGROUND: Physical and psychosocial rehabilitation following spinal cord injury (SCI) leans heavily on learning and practicing new skills. However, despite research relating motor sequence learning to spinal cord activity and clinical observations of impeded skill-learning after SCI, implicit procedural learning following spinal cord damage has not been examined. OBJECTIVE: To test the hypothesis that spinal cord injury (SCI) in the absence of concomitant brain injury is associated with a specific implicit motor sequence learning deficit that cannot be explained by depression or impairments in other cognitive measures. METHODS: Ten participants with SCI in T1-T11, unharmed upper limb motor and sensory functioning, and no concomitant brain injury were compared to ten matched control participants on measures derived from the serial reaction time (SRT) task, which was used to assess implicit motor sequence learning. Explicit generation of the SRT sequence, depression, and additional measures of learning, memory, and intelligence were included to explore the source and specificity of potential learning deficits. RESULTS: There was no between-group difference in baseline reaction time, indicating that potential differences between the learning curves of the two groups could not be attributed to an overall reduction in response speed in the SCI group. Unlike controls, the SCI group showed no decline in reaction time over the first six blocks of the SRT task and no advantage for the initially presented sequence over the novel interference sequence. Meanwhile, no group differences were found in explicit learning, depression, or any additional cognitive measures. CONCLUSIONS: The dissociation between impaired implicit learning and intact declarative memory represents novel empirical evidence of a specific implicit procedural learning deficit following SCI, with broad implications for rehabilitation and adjustment. PMID- 27355836 TI - Should Professionals Attend the Funeral? PMID- 27355838 TI - "Smoking Is Sooo ... Sandals and White Socks": Co-Creation of a Dutch Anti Smoking Campaign to Change Social Norms. AB - This article considers co-creation as a new persuasive strategy in health campaigns. Co-creation enables target audience members to become active campaign producers. A recent Dutch anti-smoking campaign applied co-creation, inviting the target audience to complete the slogan "smoking is sooo . . . " with something outdated on social networking sites (SNSs) like Facebook and Twitter to stress non-smoking as the new social norm. From a corpus-linguistic perspective, we investigated how the slogans from the target audience resonated with or deviated from the campaign's original message. In general, the target audience slogans followed the campaign's approach, but on the SNSs, differences were found regarding the valence, type of utterance, and domain to which smoking was compared. The target audience frequently compared smoking with other (inter)personal social norms. Co-creation thus provides the target audience with an opportunity to disseminate campaign messages from their own perspective, but at the same time a co-creation strategy risks diluting the intended campaign message. PMID- 27355837 TI - Clinical and genetic characterization of a large primary open angle glaucoma pedigree. AB - PURPOSE: To both characterize the clinical features of large primary open angle glaucoma (POAG) pedigree from a village in southern India and to investigate the genetic basis of their disease. MATERIALS AND METHODS: Eighty-four members of a large pedigree received complete eye examinations including slit lamp examination, tonometry, gonioscopy, and ophthalmoscopy. Some were further studied with perimetry. Those diagnosed with POAG were tested for disease-causing mutations in the myocilin and optineurin genes with Sanger sequencing. RESULTS: Fourteen of 84 family members were diagnosed with POAG, while eight were clinically judged to be POAG-suspects. The family structure and the pattern of glaucoma in the pedigree are complex. Features of glaucoma in this pedigree include relatively early age at diagnosis (mean 50 +/- 14 years) and maximum intraocular pressures ranging from 14 to 36 mm Hg with a mean of 23 mm Hg +/- 6.5 mm Hg. Patients had an average central corneal thickness (mean 529 +/- 37.8 microns) and moderate cup-to-disc ratios (0.74 +/- 0.14). No mutations were detected in myocilin, optineurin, or TANK binding kinase 1 (TBK1). CONCLUSIONS: We report a five-generation pedigree with a complex pattern of POAG inheritance that includes 22 POAG patients and glaucoma suspects. Although the familial clustering of POAG in this pedigree is consistent with dominant inheritance of a glaucoma-causing gene, mutations were not detected in genes previously associated with autosomal dominant glaucoma, suggesting the involvement of a novel disease causing gene in this pedigree. PMID- 27355839 TI - Electrochemical Red Blood Cell Counting: One at a Time. AB - We demonstrate that the concentration of a red blood cell solution under physiological conditions can be determined by electrochemical voltammetry. The magnitude of the oxygen reduction currents produced at an edge-plane pyrolytic graphite electrode was diagnosed analytically at concentrations suitable for a point-of-care test device. The currents could be further enhanced when the solution of red blood cells was exposed to hydrogen peroxide. We show that the enhanced signal can be used to detect red blood cells at a single entity level. The method presented relies on the catalytic activity of red blood cells towards hydrogen peroxide and on surface-induced haemolysis. Each single cell activity is expressed as current spikes decaying within a few seconds back to the background current. The frequency of such current spikes is proportional to the concentration of cells in solution. PMID- 27355840 TI - Dynamic PET Measures of Tau Accumulation in Cognitively Normal Older Adults and Alzheimer's Disease Patients Measured Using [18F] THK-5351. AB - BACKGROUND: [18F]THK5351, a recently-developed positron emission tomography (PET) tracer for measuring tau neurofibrillary tangle accumulation, may help researchers examine aging, disease, and tau pathology in living human brains. We examined THK5351 tracer pharmacokinetics to define an optimal acquisition time for static late images. METHODS: Primary measurements were calculation of regional values of distribution volume ratios (DVR) and standardized uptake value ratios (SUVR) in 6 healthy older control and 10 Alzheimer's disease (AD) participants. We examined associations between DVR and SUVR, searching for a 20 min SUVR time window that was stable and comparable to DVR. We additionally examined diagnostic group differences in this 20 min SUVR. RESULTS: In healthy controls, [18F]THK5351 uptake was low, with increased temporal relative to frontal binding. In AD, regional uptake was substantially higher than in healthy controls, with temporal exceeding frontal binding. Retention in cerebellar gray matter, which was used as the reference region, was low compared to other regions. Both DVR and SUVR values showed minimal change over time after 40 min. SUVR 20-40, 30-50, and 40-60 min were most consistently correlated with DVR; SUVR 40-60 min, the most stable time window, was used in further analyses. Significant (AD > healthy control) group differences existed in temporoparietal regions, with marginal medial temporal differences. We found high basal ganglia SUVR 40-60 min signal, with no group differences. CONCLUSIONS: We examined THK5351, a new PET tracer for measuring tau accumulation, and compared multiple analysis methods for quantifying regional tracer uptake. SUVR 40-60 min performed optimally when examining 20 min SUVR windows, and appears to be a practical method for quantifying relative regional tracer retention. The results of this study offer clinical potential, given the usefulness of THK5351-PET as a biomarker of tau pathology in aging and disease. PMID- 27355842 TI - The Solar System of Forking Paths: Bifurcations in Planetary Evolution and the Search for Life-Bearing Planets in Our Galaxy. PMID- 27355843 TI - Atomic Structure of Self-Assembled Monolayer of Thiolates on a Tetragonal Au92 Nanocrystal. AB - Unveiling the ligand binding mode on the crystalline surfaces is important for deciphering the long-standing structural enigma in self-assembled monolayers (SAMs). Here, the binding and patterning structures of thiolates (SR) on the Au(100) crystalline facet are revealed on the basis of the atomic structure of a highly regular, single crystalline Au92(SR)44 nanocrystal. The six exposed facets of this tetragonal nanocrystal give rise to six pieces of "nanoSAMs". We found that thiolates bind to the planar (100) facets of the nanocrystal via a simple bridge-like mode and are assembled into an overlayer with c(2 * 2) symmetry. The Au-S binding mode and translational symmetry in the kernel and on the surface of the Au92 nanocrystal can be generalized infinitely to construct the bulk two dimensional SAMs and various tetragonal nanocrystals. PMID- 27355841 TI - Convergent Mechanistic Features between the Structurally Diverse N- and O Methyltransferases: Glycine N-Methyltransferase and Catechol O-Methyltransferase. AB - Although an enormous and still growing number of biologically diverse methyltransferases have been reported and identified, a comprehensive understanding of the enzymatic methyl transfer mechanism is still lacking. Glycine N-methyltransferase (GNMT), a member of the family that acts on small metabolites as the substrate, catalyzes methyl transfer from S-adenosyl-l methionine (AdoMet) to glycine to form S-adenosyl-l-homocysteine and sarcosine. We report primary carbon ((12)C/(14)C) and secondary ((1)H3/(3)H3) kinetic isotope effects at the transferred methyl group, together with (1)H3/(3)H3 binding isotope effects for wild-type GNMT and a series of Tyr21 mutants. The data implicate a compaction effect in the methyl transfer step that is conferred by the protein structure. Furthermore, a remarkable similarity of properties is observed between GNMT and catechol O-methyltransferase, despite significant differences between these enzymes with regard to their active site structures and catalyzed reactions. We attribute these results to a catalytically relevant reduction in the methyl donor-acceptor distance that is dependent on a tyrosine side chain positioned behind the methyl-bearing sulfur of AdoMet. PMID- 27355844 TI - The influence of specimen thickness and alignment on the material and failure properties of electrospun polycaprolactone nanofiber mats. AB - Electrospinning is a versatile fabrication technique that has been recently expanded to create nanofibrous structures that mimic ECM topography. Like many materials, electrospun constructs are typically characterized on a smaller scale, and scaled up for various applications. This established practice is based on the assumption that material properties, such as toughness, failure stress and strain, are intrinsic to the material, and thus will not be influenced by specimen geometry. However, we hypothesized that the material and failure properties of electrospun nanofiber mats vary with specimen thickness. To test this, we mechanically characterized polycaprolactone (PCL) nanofiber mats of three different thicknesses in response to constant rate elongation to failure. To identify if any observed thickness-dependence could be attributed to fiber alignment, such as the effects of fiber reorientation during elongation, these tests were performed in mats with either random or aligned nanofiber orientation. Contrary to our hypothesis, the failure strain was conserved across the different thicknesses, indicating similar maximal elongation for specimens of different thickness. However, in both the aligned and randomly oriented groups, the ultimate tensile stress, short-range modulus, yield modulus, and toughness all decreased with increasing mat thickness, thereby indicating that these are not intrinsic material properties. These findings have important implications in engineered scaffolds for fibrous and soft tissue applications (e.g., tendon, ligament, muscle, and skin), where such oversights could result in unwanted laxity or reduced resistance to failure. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2794-2800, 2016. PMID- 27355845 TI - Silicon in broiler drinking water promotes bone development in broiler chickens. AB - Skeletal abnormalities, bone deformities and fractures cause significant losses in broiler production during both rearing and processing. Silicon is an essential mineral for bone and connective tissue synthesis and for calcium absorption during the early stages of bone formation. Performance was not affected by the addition of silicon. However, broilers receiving silicon showed a significant increase of phosphorus, zinc, copper, manganese and ash in the tibia. In conclusion, broiler performance was not impaired by adding the tested silicon product to the drinking water. In addition, bone development improved, as demonstrated by higher mineral and ash content. Further studies are required to determine the optimal concentration of silicon, including heat stress simulations, to better understand the effects of silicon on bone development. PMID- 27355846 TI - 18F-FDG PET/CT and Melanoma: Value of Fourth and Subsequent Posttherapy Follow-up Scans for Patient Management. AB - PURPOSE: We aimed to evaluate the added value of performing fourth and subsequent follow-up F-FDG-PET/CT scans to clinical assessment and impact on the patient's management in patients with melanoma. METHODS: This was a retrospective study of 232 biopsy-proven melanoma patients who underwent F-FDG-PET/CT scans. Of these, 71 patients had 4 or more follow-up F-FDG-PET/CT scans after completion of primary treatment, with a total of 246 fourth or subsequent follow-up PET/CT scans. The added value of each follow-up PET/CT scan to the patient's clinical assessment and treatment management was established. Kaplan-Meier plots with a Mantel-Cox log-rank test were used to establish the patient's overall survival. RESULTS: Of the 246 fourth and subsequent follow-up PET/CT scans, 61% (150/246) were negative for malignancy, and 39.0% (96/246) were positive for recurrence/metastases. FDG-PET/CT was helpful in identifying malignancy in 6.5% of the scans performed without prior clinical suspicion, which ruled out malignancy in 28.5% of the scans obtained with prior clinical signs suggestive of recurrence or for secondary therapy assessment. The PET/CT scan resulted in change of the patient's management in approximately 16.7% (41/246) of the scans. Change in management was significantly greater in patients whose scans were done with prior clinical signs suggestive of malignancy, or for therapy assessment than without prior clinical suspicion (29.3% vs 4.1%; P < 0.0001). Statistically significant difference was seen in the overall survival between patients with at least 1 positive and all negative fourth and subsequent follow-up PET/CT scans at patient level (P = 0.001). CONCLUSIONS: The fourth and subsequent F-FDG-PET/CT scans obtained after completion of primary treatment added value to clinical assessment in patients with melanoma. Patients with clinical signs suggestive of recurrence or metastases or being monitored for treatment response are more likely to benefit from the fourth or subsequent FDG PET/CT than those without prior clinical suspicion. PMID- 27355847 TI - Adrenal Metastasis of a Poorly Differentiated Adenocarcinoma Mimicking a Pheochromocytoma on 18F-FDOPA PET/CT. AB - We report the surprising intense uptake of F-FDOPA in a right adrenal metastasis of a poorly differentiated metastatic adenocarcinoma of unknown primary mimicking a pheochromocytoma in a hemodialyzed patient with the typical Menard's triad and increased serum catecholamines. Our observation emphasizes that F-FDOPA is not a specific radiotracer for pheochromocytoma and paraganglioma investigation, although it is currently and successfully used in this clinical setting. Moreover, we underline that kidney failure may be responsible for abnormally high serum catecholamines values even in subjects without pheochromocytoma, leading to erroneous diagnostic conclusions particularly in patients with adrenal masses. PMID- 27355848 TI - A Patient With Metastatic Sarcoma was Successfully Treated With Radiolabeled Somatostatin Analogs. AB - We present a sarcoma patient with a tumor reduction of more than 50% in lung metastasis after 2 single courses of the investigational medical product Lutathera (Lu-DOTA0-Tyr3-octreotate). She was resistant to more than 6 lines of therapy including all the available active drugs in soft tissue sarcomas. The high expression of somatostatin receptors was shown by microarrays and Octreoscan. The overall duration of response exceeded 1 year. PMID- 27355849 TI - Epididymal Metastasis of Prostate Cancer Detected With 68Ga-PSMA-PET/CT. AB - Here, we report on a 73-year-old man with a biochemical relapse (PSA level, 1.1 ng/mL) 8 years after radical prostatectomy and radiotherapy. Four years after primary diagnosis, a bilateral subcapsular orchiectomy was performed for endogen androgen deprivation. Physical examination and transrectal ultrasound did not show any suspicious finding. Subsequently, a Ga-PSMA-PET/CT was performed and revealed a very rare epididymal metastasis. After surgery, the PSA level decreased to less than 0.07 ng/mL, and 4 months later, the patient is still tumor free. PMID- 27355850 TI - 18F-FDG PET Detection of a Medullary Thyroid Carcinoma in a Patient With SMZL. AB - Incidental thyroid FDG uptake is not rarely encountered on PET studies. In this case, we present an incidental thyroid focus of F-FDG uptake identified in a patient with splenic marginal zone lymphoma during the baseline and the response assessment PET/CT study that proved to be medullary thyroid carcinoma on subsequent histological examination. PMID- 27355851 TI - Elevated 99mTc-MDP and 18F-NaF Uptake in a Bladder Stone. AB - An 82-year-old man with known Eddison disease, osteoporosis, and a right buttock soft tissue mass underwent Tc-MDP bone scintigraphy with SPECT/CT and F-NaF PET/CT, both of which showed elevated uptake in a bladder stone. PMID- 27355852 TI - Subacute Stroke Mimicking Cerebral Metastasis in 68Ga-PSMA-HBED-CC PET/CT. AB - A 65-year-old man with disseminated bone metastases of prostate cancer was referred for Ga-PSMA-HBED-CC-PET/CT (short PSMA-PET/CT) to exclude visceral metastases before treatment of bone metastases with Ra-dichloride. Apart from disseminated bone metastases, PSMA-PET/CT revealed a focal cerebral tracer uptake in the right frontal lobe highly suspicious for cerebral spread. According to patient history, a cerebral infarction occurred 14 days before PSMA imaging in corresponding localization confirmed by MRI scanning. This case demonstrates the possibility of false-positive finding of cerebral metastases in PSMA-PET early after stroke. PMID- 27355853 TI - Enhanced MRI and 18F-FDG PET/CT Findings of Primary Central Nervous System Lymphoma Mimicking Encephalitis. AB - We present a case of 64-year-old man with primary central nervous system lymphoma that mimicked encephalitis on enhanced MRI and F-FDG PET/CT imaging. The initial and follow-up MRI showed gradually spread high-intensity patches with nonenhancement in cortices and subcortices, while the F-FDG imaging observed mild and inhomogeneous uptake in the corresponding cerebral area particularly in the splenium of corpus callosum. This case indicates that atypical primary central nervous system lymphoma should be noted in differential diagnosis of cerebral disseminated lesions with nonenhancement in MRI or with obscure uptake of F-FDG in PET imaging (especially involving the midline of the brain). PMID- 27355854 TI - The quest for a metabolic theory of everything. PMID- 27355855 TI - Calcium intake: good for the bones but bad for the heart? An analysis of clinical studies. AB - The proper dietary calcium intake and calcium supplementation, when indicated, are important factors in the acquisition of peak bone mass during youth and in the prevention of fractures in old age. In addition to its deposition in bone, calcium confers an increase in its resistance and exhibits important activities in different enzymatic pathways in the body (e.g., neural, hormonal, muscle related and blood clotting pathways). Thus, calcium supplementation can directly or indirectly affect important functions in the body, such as the control of blood pressure, plasma glucose, body weight, lipid profile and endothelial function. Since one publication reported increased cardiovascular risk due to calcium supplementation, many researchers have studied whether this risk actually exists; the results are conflicting, and the involved mechanisms are uncertain. However, studies that have evaluated the influence of the consumption of foods rich in calcium have reported no increase in the cardiovascular risk, which suggests that nutritional intake should be prioritized as a method for supplementation and that the use of calcium supplements should be reserved for patients who truly need supplementation and are unable to achieve the recommended daily nutritional intake of calcium. PMID- 27355856 TI - Recommendations of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism for the diagnosis of Cushing's disease in Brazil. AB - Although it is a rare condition, the accurate diagnosis and treatment of Cushing's disease is important due to its higher morbidity and mortality compared to the general population, which is attributed to cardiovascular diseases, diabetes mellitus and infections. Screening for hypercortisolism is recommended for patients who present multiple and progressive clinical signs and symptoms, especially those who are considered to be more specific to Cushing's syndrome, abnormal findings relative to age (e.g., spinal osteoporosis and high blood pressure in young patients), weight gain associated with reduced growth rate in the pediatric population and for those with adrenal incidentalomas. Routine screening is not recommended for other groups of patients, such as those with obesity or diabetes mellitus. Magnetic resonance imaging (MRI) of the pituitary, the corticotropin-releasing hormone (CRH) test and the high-dose dexamethasone suppression test are the main tests for the differential diagnosis of ACTH dependent Cushing's syndrome. Bilateral and simultaneous petrosal sinus sampling is the gold standard method and is performed when the triad of initial tests is inconclusive, doubtful or conflicting. The aim of this article is to provide information on the early detection and establishment of a proper diagnosis of Cushing's disease, recommending follow-up of these patients at experienced referral centers. Arch Endocrinol Metab. 2016;60(3):267-86. PMID- 27355857 TI - Modulation and Salt-Induced Reverse Modulation of the Excited-State Proton Transfer Process of Lysozymized Pyranine: The Contrasting Scenario of the Ground State Acid-Base Equilibrium of the Photoacid. AB - Here we report on the excited-state behavior in terms of the excited-state proton transfer (ESPT) reaction as well as the ground-state acid-base property of pyranine [8-hydroxypyrene-1,3,6-trisulfonate (HPTS)] in the presence of an enzymatic protein, human lysozyme (LYZ). HPTS forms a 1:1 ground-state complex with LYZ having the binding constant KBH = (1.4 +/- 0.05) * 10(4) M(-1), and its acid-base equilibrium gets shifted toward the deprotonated conjugate base (RO( )), resulting in a downward shift in pKa. This suggests that the conjugate base (RO(-)) is thermodynamically more favored over the protonated (ROH) species inside the lysozyme matrix, resulting in an increased population of the deprotonated form. However, for the release of the proton from the excited photoacid, interestingly, the rate of proton transfer gets slowed down due to the "slow" acceptor biological water molecules present in the immediate vicinity of the fluorophore binding region inside the protein. The observed ESPT time constants, ~140 and ~750 ps, of protein-bound pyranine are slower than in bulk aqueous media (~100 ps, single exponential). The molecular docking study predicts that the most probable binding location of the fluorophore is in a region near to the active site of the protein. Here we also report on the effect of external electrolyte (NaCl) on the reverse modulation of ground-state prototropy as well as the ESPT process of the protein-bound pyranine. It is found that there is a dominant role of electrostatic forces in the HPTS-LYZ interaction process, because an increase in ionic strength by the addition of NaCl dislodges the fluorophore from the protein pocket to the bulk again. The study shows a considerably different perspective of the perturbation offered by the model macromolecular host used, unlike the available literature reports on the concerned photoacid. PMID- 27355858 TI - Effects of p-(Trifluoromethoxy)benzyl and p-(Trifluoromethoxy)phenyl Molecular Architecture on the Performance of Naphthalene Tetracarboxylic Diimide-Based Air Stable n-Type Semiconductors. AB - N,N'-Bis(4-trifluoromethoxyphenyl) naphthalene-1,4,5,8-tetracarboxylic acid diimide (NDI-POCF3) and N,N'-bis(4-trifluoromethoxybenzyl) naphthalene-1,4,5,8 tetracarboxylic acid diimide (NDI-BOCF3) have similar optical and electrochemical properties with a deep LUMO level of approximately 4.2 eV, but exhibit significant differences in electron mobility and molecular packing. NDI-POCF3 exhibits nondetectable charge mobility. Interestingly, NDI-BOCF3 shows air-stable electron transfer performance with enhanced mobility by increasing the deposition temperature onto the octadecyltrichlorosilane (OTS)-modified SiO2/Si substrates and achieves electron mobility as high as 0.7 cm(2) V(-1) s(-1) in air. The different mobilities of those two materials can be explained by several factors including thin-film morphology and crystallinity. In contrast to the poor thin film morphology and crystallinity of NDI-POCF3, NDI-BOCF3 exhibits larger grain sizes and improved crystallinities due to the higher deposition temperature. In addition, the theoretical calculated transfer integrals of the intermolecular lowest unoccupied molecular orbital (LUMO) of the two materials further show that a large intermolecular orbital overlap of NDI-BOCF3 can transfer electron more efficiently than NDI-POCF3 in thin-film transistors. On the basis of fact that the theoretical calculations are consistent with the experimental results, it can be concluded that the p-(trifluoromethoxy) benzyl (BOCF3) molecular architecture on the former position of the naphthalene tetracarboxylic diimides (NDI) core provides a more effective way to enhance the intermolecular electron transfer property than the p-(trifluoromethoxy) phenyl (POCF3) group for the future design of NDI-related air-stable n-channel semiconductor. PMID- 27355859 TI - Synthesis of Monocrystalline Nanoframes of Prussian Blue Analogues by Controlled Preferential Etching. AB - Metal cyanide coordination compounds are recognized as promising candidates for broad applications because of their tailorable and adjustable frameworks. Developing the nanostructure of a coordination compound may be an effective way to enhance the performance of that material in application-based roles. A controllable preferential etching method is described for synthesis of monocrystalline Prussian blue analogue (PBA) nanoframes, without the use of organic additives. The PBA nanoframes show remarkable rate performance and cycling stability for sodium/lithium ion insertion/extraction. PMID- 27355860 TI - Synthesis of 2-Keto-d- and l-gluconic Acid via Stereoselective Direct Aldol Reactions. AB - Stereoselective direct aldol reaction between optically pure d- or l glyceraldehyde and hydroxyacetylfuran is demonstrated as an efficient and straightforward methodology for the synthesis of six-carbon atom d- and l-arabino hex-2-ulosonic acids. syn-Selective aldol reactions realized by using either tertiary amines or a dizinc aldol catalyst constitute two parallel routes to the de novo synthesis of orthogonally protected biologically relevant 2-keto-d- and l gluconic acids. PMID- 27355862 TI - Determination of current reference viruses for serological study of swine influenza viruses after the introduction of pandemic 2009 H1N1 (pdmH1N1) in Thailand. AB - Since the introduction of pandemic H1N1 2009 virus (pdmH1N1) in pigs, the status of Thai swine influenza virus (SIV) has changed. The pdmH1N1 and its reassortant viruses have become the predominant strain circulating in the Thai swine population based on the surveillance data from 2012 to 2014. For this reason, the reference viruses for serological assays using the hemagglutination inhibition (HI) test needed to be updated. Six anti-sera against reference viruses from 2006 to 2009 (enH1N1-06, enH1N1-09, enH1N2-09, pdmH1N1-09, enH3N2-07 and enH3N2-09) were used for the HI test with four contemporary viruses (enH1N1-10, pdmH1N1-10, rH1N2 and rH3N2) and the selected reference viruses were tested with sera collected from the field to determine the current SIV status. The results showed that anti-sera of swH1N1-06 had the highest titers against enH1N1-10. Anti-sera of pdmH1N1-09 had the highest titers against pdmH1N1-10 and rH1N2, whereas, anti sera of enH3N2-09 had the highest titers against rH3N2. The results demonstrated that enH1N1-06, pdmH1N1-09 and enH3N2-09 should be selected as reference viruses for contemporary serological studies and HI tests. The seroprevalence results from 410 samples revealed enH1N1 (37.79%), pdmH1N1 (37.32%) and H3N2 (35.86%), respectively. The present study indicated that pdmH1N1 was widespread and commonly found in the Thai pig population increasing the risk of novel reassortant viruses and should be added as a reference virus for HI test. SIV surveillance program and serological studies should be conducted for the benefits of SIV control and prevention as well as monitoring for zoonotic potential. PMID- 27355861 TI - Clarithromycin resistance and prevalence of Helicobacter pylori virulent genotypes in patients from Southern Mexico with chronic gastritis. AB - In developing countries, clarithromycin resistance and frequency of re-infection are factors that contribute to high prevalence of Helicobacter pylori infection. The aim of this research was determine the prevalence of clarithromycin resistance and its relation with A2142G, A2142C and A2143G mutations in the domain V of the 23S rRNA gene of H. pylori isolates in patients from Southern Mexico with chronic gastritis. Another purpose of this work was to study the prevalence of virulent genotypes and distribution of resistant strains according to the vacA/cagA/babA2 H. pylori genotypes. One hundred forty-four patients with chronic gastritis were studied. Forty-five H. pylori strains were isolated and clarithromycin susceptibility was determined by the disk-diffusion method. The 82.2% of the strains had the combination of alleles vacA s1 m1 and the cagA gene was detected in 77.8% and 40% of the strains were babA2 positive. The vacA s1 m1 genotype was detected more frequently in cagA(+) strains, vacA s1m1/cagA(+)/babA2(-) genotype was more frequent than vacA s1m1/cagA(+)/babA2(+), 37.8% and 33.3%, respectively. Eight strains were clarithromycin resistant, in three of these, point mutations were identified, but only in one strain the A2143G mutation associated with clarithromycin resistance was found. Other point mutations (A1821G, G1826A, T1830C, A2089G, T1600C, C1601T, C1602T, T1610C, A1611C and T1633G) that have not been associated with clarithromycin resistance were identified. The highest proportion of resistant strains was vacA s1m1/cagA(+) (62.5%). In patients from southern Mexico with chronic gastritis, the prevalence of clarithromycin resistance is within internationally accepted range (17.8%) and allows continued use of triple therapy for H. pylori eradication. However, it is necessary to monitor the evolution of clarithromycin resistance in this area. The largest proportion of resistant H. pylori strains is not harboring the A2142G, A2142C and A2143G mutations in the 23S rRNA gene (87.5%). The vacA s1m1/cagA(+) genotype was the most prevalent and among clarithromycin-resistant strains, this was the predominant. PMID- 27355864 TI - 40th Annual Congress of the Italian Urodynamic Society, Universita degli Studi di Perugia, Perugia, Italy, June 23-25, 2016. PMID- 27355863 TI - A Molecular-Level Account of the Antigenic Hantaviral Surface. PMID- 27355865 TI - Early matrix metalloproteinase-9 concentration in the first 48 h after aneurysmal subarachnoid haemorrhage predicts delayed cerebral ischaemia: An observational study. AB - BACKGROUND: Delayed cerebral ischaemia from vasospasm is an important cause of complications and death after aneurysmal subarachnoid haemorrhage. There is currently no established biomarker for identifying patients at high risk of delayed cerebral ischaemia. OBJECTIVE: Considering the important role of inflammation in the pathogenesis of delayed cerebral ischaemia, we investigated whether matrix metalloproteinase-9 (MMP-9) may be an efficient biomarker for predicting elayed cerebral ischaemia after subarachnoid haemorrhage. DESIGN: Single-centre prospective observational study. SETTING: Neuroscience Critical Care Unit of a teaching hospital. PARTICIPANTS: Thirty consecutive patients with severe subarachnoid haemorrhage requiring external ventricular drainage were enrolled during 2013 and 2014. INTERVENTIONS: Blood and cerebrospinal fluid (CSF) were sampled within the first 24 h and between 48 and 72 h after admission. We evaluated the activity and concentrations of MMP-9 and endothelin-1 with zymography and ELISA. Patients were allocated to groups with delayed cerebral ischaemia (n = 16) or without delayed cerebral ischaemia (n = 14). RESULTS: Within 24 h, median [interquartile range] MMP-9 concentrations in CSF were significantly higher in patients with delayed cerebral ischaemia (47 [21 to 102] ng ml) than in those without delayed cerebral ischaemia (4 [2 to 13] ng ml, P = 0.001). CSF MMP-9 activity and endothelin-1 concentrations were correlated (r = 0.6, P = 0.02). The areas under the receiver operating characteristic curves were 0.73 (95% confidence interval [0.53 to 0.87]) and 0.91 (95% confidence interval [0.75 to 0.98]) for MMP-9 concentrations in plasma and CSF, respectively, at 24 h to predict delayed cerebral ischaemia CSF MMP-9 concentrations more than 14.3 ng ml at 24 h predicted the occurrence of delayed cerebral ischaemia with a sensitivity and specificity of 88 and 86%, respectively. After multivariate logistic analysis, only CSF MMP-9 concentrations at 24 h predicted the occurrence of delayed cerebral ischaemia (P = 0.01). CONCLUSION: MMP-9 concentrations in both plasma and CSF, measured within 48 h after subarachnoid haemorrhage, were highly predictive of the occurrence of delayed cerebral ischaemia within the first 2 weeks. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02397759. PMID- 27355866 TI - Awake, sedated or anaesthetised for regional anaesthesia block placements?: A retrospective registry analysis of acute complications and patient satisfaction in adults. AB - BACKGROUND: Whether adults should be awake, sedated or anaesthetised during establishment of regional anaesthesia is still debated and there is little information on the relative safety of each. In paediatric practice, there is often little choice but to use sedation or anaesthesia as otherwise the procedures would be too distressing and patient movement would be hazardous. OBJECTIVE(S): The objective of this study was to evaluate complications related to central and peripheral regional block and patient satisfaction in awake, sedated and anaesthetised adult patients. DESIGN: A retrospective registry analysis. SETTING: The German Network of Regional Anaesthesia database was analysed between 2007 and 2012. PATIENTS: We included data of 42 654 patients and defined three groups: group I awake (n = 25 004), group II sedated (n = 15 121) and group III anaesthetised (n = 2529) for block placement. MAIN OUTCOME MEASURES: Odds ratios [OR; 95% confidence interval (CI)] were calculated with logistic regression analysis and adjusted for relevant confounders to determine the risk of block-related complications in sedated or anaesthetised patients compared with awake patients. RESULTS: Rates of local anaesthetic systemic toxicity were comparable between the groups [awake 0.02% (95% CI: 0.002 to 0.0375), sedated 0.02% (0.003 to 0.042) and anaesthetised 0% (0 to 0.12%)], as were the rates of pneumothorax [awake 0.035% (0 to 0.074), sedated 0% (0 to 0.002) and anaesthetised 0.2% (0 to 0.56)]. Considering peripheral nerve blocks, sedated patients had a decreased risk for multiple skin puncture [adjusted OR: 0.78 (95% CI: 0.71 to 0.85), premature termination [0.45 (0.22 to 0.91)], primary failure [0.58 (0.40 to 0.83)] and postoperative paraesthesia [0.35 (0.28 to 0.45)], but an increased risk for a bloody tap [1.82 (1.50 to 2.21)]. General anaesthesia increased the risk of a bloody tap [adjusted OR: 1.33 (95% CI: 1.01 to 1.78)] and multiple skin puncture [1.28 (1.12 to 1.46)], but decreased the risk for postoperative paraesthesia [0.16 (0.06 to 0.38)]. In neuraxial sites, sedation increased the risk for multiple skin puncture [adjusted OR: 1.18 (95% CI: 1.09 to 1.29)], whereas block placement under general anaesthesia decreased the risk for multiple skin puncture [0.53 (0.39 to 0.72)] and bloody tap but significantly increased the risk for postoperative paraesthesia related to a catheter [2.45 (1.19 to 5.02)]. Sedation was associated with a significant improvement in patient satisfaction. CONCLUSION: Sedation may improve safety and success of peripheral nerve block placement. Block placement under general anaesthesia in adults should be reserved for experienced anaesthesiologists and special situations. PMID- 27355867 TI - Arg188 drives RhoC membrane binding. AB - RhoA and RhoC GTPases are 92% identical but demonstrate unique regulation and function. Phosphorylation of Ser188 has widely been reported to inhibit RhoA activity. RhoC possesses Arg188 in place of Ser188 but retains a canonical upstream PKA recognition sequence. We report here that RhoC-R188S was a PKA substrate in vitro and exhibited less GTP loading compared to wild-type RhoC when expressed in cells. Transiently expressed RhoC was found to be significantly more membrane associated than RhoA. Membrane association of RhoC-R188S and RhoC-R188A were similar to each other and wild-type RhoA, suggesting that Arg188 directly promotes RhoC membrane binding. The positive influence of Arg188 on RhoC membrane association was evident in a constitutively active (Q63L) background. In accordance, RhoA-S188R was significantly more membrane associated than either RhoA or RhoA-S188A. Altogether, these data suggest that swapping residue 188 identity effectively flips the membrane binding profile of wild-type RhoA and RhoC through positive arginine contribution rather than negative phosphoserine regulation. PMID- 27355868 TI - Assessing efficacy of a retention in care intervention among HIV patients with depression, anxiety, heavy alcohol consumption and illicit drug use: Erratum. PMID- 27355869 TI - HIV infection is independently associated with frailty in middle-aged HIV type 1 infected individuals compared with similar but uninfected controls: Erratum. PMID- 27355870 TI - Impact and economic evaluations of a combination prevention programme for men who have sex with men in Mexico: Erratum. PMID- 27355871 TI - Gallium and Functionalized-Porphyrins Combine to Form Potential Lysosome-Specific Multimodal Bioprobes. AB - A water-soluble bimetallic normal ("cold") and radiochemical ("hot") gallium porphyrin-ruthenium-bipyridine complex (GaporRu-1) has been synthesized by microwave methodology in short reaction times with good (>85%) yields. (68)GaporRu-1 is demonstrated to be a potential multimodal and functional bioprobe for positron emission tomography (PET), lysosome specific optical imaging, and photodynamic therapy. PMID- 27355872 TI - TCGA: Increased oncoprotein coding region mutations correlate with a greater expression of apoptosis-effector genes and a positive outcome for stomach adenocarcinoma. AB - Oncogene mutations are primarily thought to facilitate uncontrolled cell growth. However, overexpression of oncoproteins likely leads to apoptosis in a feed forward mechanism, whereby a certain level of oncoprotein leads to the activation of pro-proliferation effector genes and higher levels lead to activation of pro apoptotic effector genes. TCGA STAD barcodes having no oncoprotein coding region mutations represented reduced expression of the apoptosis-effector genes compared with barcodes with multiple oncoprotein coding region mutations. Furthermore, STAD barcodes in a "no-subsequent tumor" group, representing 224 samples, and in a "positive outcome" group, had more oncoprotein coding regions mutated, on average, than barcodes of the new tumor and negative outcome groups, respectively. BRAF, CTNNB1, KRAS and MTOR coding region mutations (as a group) had the strongest association with the no-subsequent tumor group. Tumor suppressor coding region mutations were also correlated with no-subsequent tumor. These results are consistent with an oncoprotein-mediated, feed-forward mechanism of apoptosis in patients. Importantly, the no-subsequent tumor group also had more overall mutations. This result leads to considerations of unhealthy cells or cells with more neo-antigens for immune rejection. However, a probabilistic aspect of mutagenesis is also consistent with more oncoprotein and tumor suppressor protein mutations, in cases of more overall mutations, and thus a higher likelihood of activation of feed forward apoptosis pathways. PMID- 27355873 TI - Physician-Industry Interactions and Anti-Vascular Endothelial Growth Factor Use Among US Ophthalmologists. PMID- 27355875 TI - Computational Study Exploring the Interaction Mechanism of Benzimidazole Derivatives as Potent Cattle Bovine Viral Diarrhea Virus Inhibitors. AB - Bovine viral diarrhea virus (BVDV) infections are prevailing in cattle populations on a worldwide scale. The BVDV RNA-dependent RNA polymerase (RdRp), as a promising target for new anti-BVDV drug development, has attracted increasing attention. To explore the interaction mechanism of 65 benzimidazole scaffold-based derivatives as BVDV inhibitors, presently, a computational study was performed based on a combination of 3D-QSAR, molecular docking, and molecular dynamics (MD) simulations. The resultant optimum CoMFA and CoMSIA models present proper reliabilities and strong predictive abilities (with Q(2) = 0. 64, R(2)ncv = 0.93, R(2)pred = 0.80 and Q(2) = 0. 65, R(2)ncv = 0.98, R(2)pred = 0.86, respectively). In addition, there was good concordance between these models, molecular docking, and MD results. Moreover, the MM-PBSA energy analysis reveals that the major driving force for ligand binding is the polar solvation contribution term. Hopefully, these models and the obtained findings could offer better understanding of the interaction mechanism of BVDV inhibitors as well as benefit the new discovery of more potent BVDV inhibitors. PMID- 27355876 TI - Polyglycolic acid sheet application for intractable acute hemorrhagic rectal ulcer. PMID- 27355877 TI - Acceptor and Excitation Density Dependence of the Ultrafast Polaron Absorption Signal in Donor-Acceptor Organic Solar Cell Blends. AB - Transient absorption spectroscopy on organic semiconductor blends for solar cells typically shows efficient charge generation within ~100 fs, accounting for the majority of the charge carriers. In this Letter, we show using transient absorption spectroscopy on blends containing a broad range of acceptor content (0.01-50% by weight) that the rise of the polaron signal is dependent on the acceptor concentration. For low acceptor content (<10% by weight), the polaron signal rises gradually over ~1 ps with most polarons generated after 200 fs, while for higher acceptor concentrations (>10%) most polarons are generated within 200 fs. The rise time in blends with low acceptor content was also found to be sensitive to the pump fluence, decreasing with increasing excitation density. These results indicate that the sub-100 fs rise of the polaron signal is a natural consequence of both the high acceptor concentrations in many donor acceptor blends and the high excitation densities needed for transient absorption spectroscopy, which results in a short average distance between the exciton and the donor-acceptor interface. PMID- 27355874 TI - Discovery of a Highly Selective Glycogen Synthase Kinase-3 Inhibitor (PF 04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging. AB - Glycogen synthase kinase-3 (GSK-3) regulates multiple cellular processes in diabetes, oncology, and neurology. N-(3-(1H-1,2,4-triazol-1-yl)propyl)-5-(3 chloro-4-methoxyphenyl)oxazole-4-carboxamide (PF-04802367 or PF-367) has been identified as a highly potent inhibitor, which is among the most selective antagonists of GSK-3 to date. Its efficacy was demonstrated in modulation of tau phosphorylation in vitro and in vivo. Whereas the kinetics of PF-367 binding in brain tissues are too fast for an effective therapeutic agent, the pharmacokinetic profile of PF-367 is ideal for discovery of radiopharmaceuticals for GSK-3 in the central nervous system. A (11) C-isotopologue of PF-367 was synthesized and preliminary PET imaging studies in non-human primates confirmed that we have overcome the two major obstacles for imaging GSK-3, namely, reasonable brain permeability and displaceable binding. PMID- 27355878 TI - Parenting and Preschooler TV Viewing in Low-Income Mexican Americans: Development of the Parenting Practices Regarding TV Viewing (PPRTV) Scale. AB - OBJECTIVE: To develop and test a comprehensive, culturally based measure of parenting practices regarding television (TV) viewing in low-income Mexican American mothers of preschoolers. METHOD: Low-income Mexican-American female primary caregivers of preschoolers were recruited in urban safety-net pediatric clinics during the 2013 to 2014 academic year. Items on parenting practices regarding TV viewing were developed from a prior scale, review of the literature, and results from semistructured interviews. Items were administered by phone, and analyses included evaluation of the factor structure and psychometric properties of a 40-item measure of parenting practices regarding TV viewing (PPRTV). RESULTS: Using exploratory factor analysis, a 7-factor model emerged as the best fit for the data representing the following domains of parenting practices: time restriction, behavioral control, instructive practices, coviewing, planful restriction, reactive content restriction, and commercial endorsement. Internal reliabilities were acceptable (Cronbach's alpha >.75). Correlations among the resulting subscales were small to moderate (rs = 0.01-0.43). Subscales were correlated with child TV viewing amounts: time restriction (-0.14, p < .05); behavioral control (0.27, p < .001); coviewing (0.16, p < .01); planful restriction (-0.20, p < .001); and commercial endorsement (0.11, p < .05), which provides support for construct validity. CONCLUSION: The PPRTV scale measures 7 domains of parenting practices and has good initial reliability and validity. It allows investigators to conduct more in-depth evaluations of the role parents play in socializing young children on TV use. Results of such work will be important to informing the design of interventions aiming to ensure healthy screen media habits in young children. PMID- 27355879 TI - Visuomotor Function in School-Age Children with Single-Suture Craniosynostosis. AB - OBJECTIVE: Previous studies have shown that infants and young children with single-suture craniosynostosis (SSC) perform more poorly on tests of visuomotor function than children without SSC. However, previous studies are limited by small sample sizes and little is known about the persistence of visuomotor problems into the school-age years. The aim of this study was to compare visuomotor function in children with and without SSC at the beginning of elementary school. METHODS: The study included 179 children with SSC (cases) and 183 children without SSC (controls). Visuomotor function was measured by the NEPSY-II Arrows, the Purdue Pegboard Test, and the Beery-Buktenica Developmental Test of visual-motor integration. Case-control differences were estimated using linear regression, adjusted for age, sex, socioeconomic status, and maternal IQ. RESULTS: Cases scored more poorly on all measures of visuomotor function, although the magnitude of case-control differences varied across measures. The greatest differences were observed for the Purdue Pegboard Test, with an average adjusted difference of -0.2 to -0.4 SD points (p-values ranged from .008 to .05). Case-control differences were small in magnitude for other measures of visuomotor function, ranging from -0.01 to -0.1 SD points (p-values ranged from .22 to .88). CONCLUSION: Children with SSC experienced deficits in manual dexterity into the school-age years but were similar to children without SSC on measures of visual processing. These findings advocate for the assessment of fine-motor function as part of school readiness evaluations in children with SSC. PMID- 27355880 TI - Snapshots of Growing Up: Youth with Autism Explore Adulthood Through Photovoice. AB - OBJECTIVE: Youth with autism spectrum disorder (ASD) experience significant challenges transitioning to adulthood. We utilized Photovoice to better understand youth's desires for and perspectives on becoming adults. METHOD: Youth with ASD (N = 11) photographed their life experiences, attended group and individual photo-sharing and discussion sessions, and exhibited their work publicly. Thematic analysis was used to identify salient recurring patterns in the data. RESULTS: Thematic analysis identified important topics in session transcripts and 184 photographs. Youth with ASD expressed many perspectives about their adult lives, which centered around 3 themes: the meaning of adulthood; desire for independent living; and employment goals. CONCLUSION: Findings identified what youth with ASD want and need to achieve adulthood. This study demonstrated the utility of a new methodology to provide opportunities for youth to share their experiences and define their priorities. PMID- 27355884 TI - Acute Agitation and Self-Injury in a 5-Year Old with Autism. AB - CASE: A 5-year-old nonverbal child with autism spectrum disorder (ASD) was admitted to inpatient pediatrics with new onset agitation and self-injurious behavior. His parents described him as a pleasant child without previous episodes of self-injury. Four days before admission, the parents noted new irritability followed by 2 days of self-injury to the face without clear precipitant. His hitting intensified with closed fist to face, and he required parental physical restraint to prevent further injury. Car rides and ibuprofen provided only temporary relief. He consumed minimal liquid and ate no solid food for 2 days. The parents denied any changes to the environment or routine and denied recent travel, sick contacts, fevers, cough, otalgia, vomiting, diarrhea, and constipation. The patient had been diagnosed with ASD at age 18 months old but had no other significant medical history.On examination, the child was alert but distressed and restless, wearing padded mitts as his parents attempted to calm him by pushing him in a stroller. He had multiple areas of severe bruising and facial swelling in the right periorbital area, cheek, and jaw. The rest of the physical examination was unremarkable. Laboratory results included a leukocytosis with left shift, a normal metabolic panel, and an elevated creatine kinase. Other investigations included a normal lumber puncture, chest radiograph, head and face computerized tomography without contrast, and brain magnetic resonance imaging. A dentist consultant examined him and noted an erupting molar but no decay or abscesses. A psychiatric evaluation was requested as there was no clear medical source for the patient's distress. PMID- 27355882 TI - Reply. PMID- 27355881 TI - Social Competence in Childhood Brain Tumor Survivors: Feasibility and Preliminary Outcomes of a Peer-Mediated Intervention. AB - OBJECTIVE: Evaluate the acceptability, feasibility, and preliminary outcomes of a peer-mediated intervention to improve social competence of brain tumor survivors and classmates. METHOD: Twelve childhood brain tumor survivors and 217 classroom peers in intervention (n = 8) or comparison (n = 4) classrooms completed measures of social acceptance and reputation at 2 time points in the year. The intervention (5-8 sessions over 4-6 weeks) taught peer leaders skills for engaging classmates. Individual and classroom outcomes were analyzed with analysis of covariance. RESULTS: Recruitment rates of families of brain tumor survivors (81%) and schools (100%) were adequate. Peer leaders reported satisfaction with the intervention. Preliminary outcome data trended toward some benefit in increasing the number of friend nominations for survivors of brain tumors but no changes in other peer-reported metrics. Preliminary results also suggested some positive effects on classroom levels of victimization and rejection. CONCLUSION: A peer-mediated intervention was acceptable to families of brain tumor survivors and feasible to implement in schools. Findings warrant a larger trial to evaluate improvements for children with brain tumors and their peers. PMID- 27355885 TI - Bedtime Electronic Media Use and Sleep in Children with Autism Spectrum Disorder. AB - OBJECTIVES: The purpose of this study was to better understand the use of screen based media at bedtime among children with autism spectrum disorder (ASD). The study specifically examined whether the presence of media devices in the child's bedroom, the use of media as part of the bedtime routine, and exposure to media with violent content just before bedtime were associated with sleep difficulties. METHODS: Parents of 101 children with ASD completed questionnaires assessing their children's sleep habits, bedroom media access (including television, video game devices, and computers), and patterns of nighttime media use (including timing of media exposure and violent media content). RESULTS: Children with ASD who used media as part of the bedtime routine showed significantly greater sleep onset latency than those who did not (39.8 vs 16.0 minutes). Similarly, children who were exposed to media with violent content within the 30-minute period before bedtime experienced significantly greater sleep onset delays and shorter overall sleep duration. In contrast, the mere presence of bedroom media was not associated with either sleep onset latency or sleep duration. CONCLUSION: Overall, these findings indicate that incorporating television and video games into the bedtime routine is associated with sleep onset difficulties among children with ASD. Exposure to violent media before bed is also associated with poor sleep. Families of children with ASD should be encouraged to regulate and monitor the timing and content of television and video game use, whether or not such devices are physically present in the child's bedroom. PMID- 27355887 TI - Response to "Behavioral Management of Sleep Problems in Infants Under 6 Months - What Works?". PMID- 27355886 TI - The Effect of Bilingual Exposure on Executive Function Skills in Preterm and Full Term Preschoolers. AB - OBJECTIVE: To evaluate the effects of bilingual exposure on executive function (EF) skills, measured by parent-rating and performance-based instruments, in preterm and full-term preschoolers. METHOD: Children age 3 to 5 years (mean 4.4) born preterm (PT; n = 82) and full term (FT; n = 79) had monolingual (PT-M, n = 51; FT-M, n = 53) or bilingual (PT-B, n = 31; FT-B, n = 26) language exposure. Groups were similar in age, gender and race, but PT children had lower socioeconomic status (SES) than FT children. Parents completed a language questionnaire and diary and a standardized parent rating of EF skills. Children completed EF tasks that tap response inhibition, working memory, and cognitive flexibility. ANCOVA and logistic regression examined effects on EF of birth group (PT/FT), language status (M/B), and birth group by language status interaction, controlling for age and SES. RESULTS: Compared to children born FT, children born PT had significantly higher parent-rated EF scores and poorer performance on all but one EF task, both indicating more EF problems. No main effects of language status and no birth group by language status interactions were significant. CONCLUSION: PT status was clearly associated with poorer EF skills, similar to many other studies. In this sample, bilingual exposure conferred neither an advantage nor disadvantage in the FT and PT group. This information may prove useful in counseling families of both PT and FT children about the impact of bilingual exposure on their children's cognitive skills. PMID- 27355888 TI - Inside Children's Emotions: Thoughts on Pixar's Inside Out. PMID- 27355889 TI - Attention-Deficit/Hyperactivity Disorder-Related Impulsivity and Cyberbullying in Social Media. AB - CASE: Sarah is a 13-year-old eighth grader who was recently diagnosed for the first time with attention-deficit/hyperactivity disorder (ADHD)-inattentive type, and the family elected to treat her with behavioral interventions to help her organization and attention. She had struggled with distractibility and disorganization since the fourth grade. At home, Sarah's mother described her as "spacey" and unable to complete the morning routine without constant supervision. Over time, her mother observed that it seemed as if Sarah had given up on school.As Sarah became an adolescent, her self-esteem suffered because of her academic struggles, and she placed increasing emphasis on her appearance, including focus on remaining thin and refusing to leave the house without makeup. It was in this context that Sarah recently posted photographs of herself in various stages of undress and/or drinking alcohol on Snapchat, a photograph sharing application in which users can send "snaps"-photographs that disappear soon after opening. However, snap recipients can take a screenshot or photograph of the snap, thereby saving the image. For unknown reasons, Sarah's close female friend took screenshots of these provocative photographs and sent them to their classmates and Sarah's older brother.Sarah's family contacted the police and has been working with her school to address this incident. This experience resulted in significant family stress and distrust of Sarah. For example, her mother took away her cell phone and laptop and has "grounded her" for a month from all out of school activities.Sarah's family seeks guidance regarding teaching Sarah about using social media responsibly and preventing this from happening again. Sarah's mom comes to your urgent care session asking for help because she does not feel that Sarah has "learned her lesson." What would you do next? PMID- 27355890 TI - Guiding Trainee Pediatricians About How to Cope with Grief. PMID- 27355891 TI - The role of memory in posttraumatic stress disorder: implications for clinical practice. AB - INTRODUCTION: Posttraumatic stress disorder (PTSD) is a highly prevalent disorder with important social consequences. Several models have been developed with the aim of understanding the mechanisms underlying its symptoms. Intrusions are idiosyncratic symptoms that commonly take the form of involuntary recollection of images or flashbacks about the traumatic event. OBJECTIVE: To review how memory is conceptualized in each of these models and the implications for clinical practice. METHODS: A narrative review of the literature was conducted through analysis of the perspectives of memory in theoretical models of PTSD. RESULTS: Two main perspectives were identified: 1) models in which specific mechanisms of memory for processing traumatic events are proposed, especially those based on clinical studies, and 2) models in which common mnemonic mechanisms are utilized to explain the phenomenon, primarily based on basic experimental research studies investigating memory. The different theories based on these approaches have led to distinct psychotherapy interventions. CONCLUSION: In order to clarify these discrepancies, future research should aim for the methodological rigor of experimental studies, while maintaining the ecological applicability of findings. Cognitive experimental psychopathology is therefore an area on which research funding should be focused. Such studies could elucidate the role of mnemonic aspects in PTSD and how they impact psychological treatments. PMID- 27355892 TI - Development of Brazilian prototypes for short-term psychotherapies. AB - INTRODUCTION: The Psychotherapy Process Q-Set (PQS) prototype method is used to measure the extent to which ideal processes of different psychotherapies are present in real cases, allowing researchers to examine how adherence to these models relates to or predicts change. Results from studies of short-term psychotherapies suggest that the original psychodynamic prototype is more suitable for studying psychoanalysis and long-term psychodynamic psychotherapy than its time-limited counterparts. Furthermore, culture probably influences how therapies are typically conducted in a given country. Therefore, it seems appropriate to develop Brazilian prototypes on which to base studies of short term psychodynamic and cognitive-behavioral processes in this country. OBJECTIVE: To develop prototypes for studying processes of short-term psychotherapies and to examine the degree of adherence of two real psychotherapy cases to these models. METHODS: Expert clinicians used the PQS to rate a hypothetical ideal session of either short-term psychodynamic psychotherapy (STPP) or cognitive-behavioral therapy (CBT). Ratings were submitted to Q-type factor analysis to confirm the two groups. Regressive factor scores were rank ordered to describe the prototypes. These ideal models were correlated with ratings of actual therapy processes in two complete psychotherapy cases, one STPP and the other CBT. RESULTS: Agreement levels between expert ratings were high and the two ideal models were confirmed. As expected, the PQS ratings for actual STPP and CBT cases had significant correlations with their respective ideal models, but the STPP case also adhered to the CBT prototype. CONCLUSION: Overall, the findings reveal the adequacy of the prototypes for time-limited therapies, providing initial support of their validity. PMID- 27355893 TI - Revision of the grandiosity dimension of the Dimensional Clinical Personality Inventory and verification of its psychometric properties. AB - INTRODUCTION: Personality disorders are among the most common disorders seen in clinical psychology. However, in Brazil there are few instruments for assessing the pathological characteristics of personality. OBJECTIVE: To revise the grandiosity dimension of the Brazilian Dimensional Clinical Personality Inventory (Inventario Dimensional Clinico da Personalidade [IDCP]) and investigate its psychometric properties. METHODS: A total of 225 people participated in this study. Their ages ranged from 18 to 66 years (mean [M] = 26.2, standard deviation [SD] = 8.1) and the majority were female (n = 162, 70.1%). The IDCP and the Brazilian versions of the Revised NEO Personality Inventory (NEO PI-R) and the Personality Inventory for DSM-5 (PID-5) were administered to all participants. RESULTS: A total of 285 new items were developed and content analysis was used to select 33 of these to comprise the final version destined for administration. The results of parallel analysis and factor analysis identified four interpretable factors. Internal consistency coefficients were deemed acceptable and varied from 0.73 to 0.84 for the factors. Additionally, the expected correlations between the IDCP Inventory and the other tests were observed. CONCLUSION: This study demonstrates the revised dimension's suitability for assessment of the pathological traits of narcissistic personality disorder. PMID- 27355894 TI - Assessment of dependence and anxiety among benzodiazepine users in a provincial municipality in Rio Grande do Sul, Brazil. AB - INTRODUCTION: Benzodiazepines are among the most prescribed drugs for anxiety and one of the most used drug classes in the world and have a high potential for addiction. The objective of this study was to assess levels of dependence and anxiety among users of these drugs in the public health system. METHODS: This was a cross-sectional, descriptive and quantitative study. Benzodiazepine users treated on the public health system were selected. Anxiety levels were assessed with the Hamilton Anxiety Scale and dependency with the Benzodiazepine Dependence Self-Report Questionnaire. RESULTS: Benzodiazepine use was higher among women and in older age groups. Duration of benzodiazepine use was greater than 1 year for all respondents. The dependence assessment indicated that more than half of users were dependent on taking benzodiazepines and most had a severe degree of anxiety. CONCLUSION: This study found evidence of prolonged and inappropriate use of benzodiazepines. It is necessary to educate users about the risks of these drugs and to develop strategies to rationalize use of these drugs by working with prescribers and dispensers. PMID- 27355895 TI - Spontaneous seizures after ECT in a patient medicated with bupropion, sertraline and risperidone. AB - Objective:: To report a case of post-electroconvulsive therapy spontaneous seizures in a patient medicated with sertraline, bupropion and risperidone. Case description:: A 53-year-old woman with recurrent major depression was admitted to our psychiatry department for a major depressive episode of 6 weeks' duration, with psychotic symptoms. She was already on 200 mg/day of sertraline and 2 mg/day of risperidone. After 8 weeks on 200 mg/day of sertraline, 4 mg/day of risperidone and slow release bupropion (titrated to 300 mg/day), with no objective improvements, the decision was taken to initiate a course of 8-10 electroconvulsive therapy (ECT) sessions. Two days after the first treatment, three generalized tonic-clonic seizures occurred within 6 hours. Phenytoin and sodium valproate were added to the patient's daily medication and no further spontaneous seizures were observed. After neurologic assessment and discussion of the case, phenytoin and bupropion were withdrawn at once (two days after the spontaneous seizures) and the decision was taken to resume the ECT treatment. No further spontaneous seizures occurred and, at discharge, the patient exhibited significant improvements and was free from major depressive symptoms. Comments:: This report illustrates a case of post-ECT spontaneous seizures that might have been due to a specific pharmacological etiological pathway, namely, bupropion's proconvulsive properties, although both sertraline and risperidone also lower the convulsive threshold. PMID- 27355896 TI - Choice of osteoblast model critical for studying the effects of electromagnetic stimulation on osteogenesis in vitro. AB - The clinical benefits of electromagnetic field (EMF) therapy in enhancing osteogenesis have been acknowledged for decades, but agreement regarding the underlying mechanisms continues to be sought. Studies have shown EMFs to promote osteoblast-like cell proliferation, or contrarily, to induce differentiation and enhance mineralization. Typically these disparities have been attributed to methodological differences. The present paper argues the possibility that the chosen osteoblast model impacts stimulation outcome. Phenotypically immature cells, particularly at low seeding densities, appear to be prone to EMF-amplified proliferation. Conversely, mature cells at higher densities seem to be predisposed to earlier onset differentiation and mineralization. This suggests that EMFs augment ongoing processes in cell populations. To test this hypothesis, mature SaOS-2 cells and immature MC3T3-E1 cells at various densities, with or without osteo-induction, were exposed to sinusoidal 50 Hz EMF. The exposure stimulated the proliferation of MC3T3-E1 and inhibited the proliferation of SaOS 2 cells. Baseline alkaline phosphatase (ALP) expression of SaOS-2 cells was high and rapidly further increased with EMF exposure, whereas ALP effects in MC3T3-E1 cells were not seen until the second week. Thus both cell types responded differently to EMF stimulation, corroborating the hypothesis that the phenotypic maturity and culture stage of cells influence stimulation outcome. PMID- 27355897 TI - Periventricular Nodular Heterotopia: Detection of Abnormal Microanatomic Fiber Structures with Whole-Brain Diffusion MR Imaging Tractography. AB - Purpose To investigate whether it is possible in patients with periventricular nodular heterotopia (PVNH) to detect abnormal fiber projections that have only previously been reported in the histopathology literature. Materials and Methods Whole-brain diffusion-weighted (DW) imaging data from 14 patients with bilateral PVNH and 14 age- and sex-matched healthy control subjects were prospectively acquired by using 3.0-T magnetic resonance (MR) imaging between August 1, 2008, and December 5, 2012. All participants provided written informed consent. The DW imaging data were processed to generate whole-brain constrained spherical deconvolution (CSD)-based tractography data and super-resolution track-density imaging (TDI) maps. The tractography data were overlaid on coregistered three dimensional T1-weighted images to visually assess regions of heterotopia. A panel of MR imaging researchers independently assessed each case and indicated numerically (no = 1, yes = 2) as to the presence of abnormal fiber tracks in nodular tissue. The Fleiss kappa statistical measure was applied to assess the reader agreement. Results Abnormal fiber tracks emanating from one or more regions of heterotopia were reported by all four readers in all 14 patients with PVNH (Fleiss kappa = 1). These abnormal structures were not visible on the tractography data from any of the control subjects and were not discernable on the conventional T1-weighted images of the patients with PVNH. Conclusion Whole brain CSD-based fiber tractography and super-resolution TDI mapping reveals abnormal fiber projections in nodular tissue suggestive of abnormal organization of white matter (with abnormal fibers both within nodules and projecting to the surrounding white matter) in patients with bilateral PVNH. (c) RSNA, 2016. PMID- 27355898 TI - Underestimation Rate at MR Imaging-guided Vacuum-assisted Breast Biopsy: A Multi Institutional Retrospective Study of 1509 Breast Biopsies. AB - Purpose To assess the rate of underestimation of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) at magnetic resonance (MR) imaging guided vacuum-assisted breast biopsy and to explore the imaging, demographic, and histologic characteristics associated with lesion upgrade after surgery. Materials and Methods This retrospective study had institutional review board approval, and the need to obtain informed patient consent was waived. A total of 1509 MR imaging-guided vacuum-assisted biopsy procedures were performed in nine centers. A diagnosis of ADH was obtained after biopsy in 72 cases, and a diagnosis of DCIS was obtained in 118 cases. Pearson chi2 and Fisher tests were used to assess the association between demographic, MR imaging, and biopsy features and lesion upgrade. Univariate statistical analyses were performed, and each significant parameter was entered into a multivariate logistic regression analysis. Results Surgical excision was performed in 66 of the 72 ADH cases and in 117 of 118 DCIS cases. The ADH and DCIS underestimation rates were 25.8% (17 of 66) and 23.1% (27 of 117), respectively. Underestimation was 5.6-fold (odds ratio [OR] = 5.6; 95% confidence interval [CI]: 1.7, 18.3) and 3.6-fold (OR = 3.6; 95% CI: 1.2, 10) more likely in mass (n = 20 for ADH and n = 20 for DCIS) than in non-mass (n = 46 for ADH and n = 97 for DCIS), compared with nonunderestimation, in ADH and DCIS respectively. At multivariate analysis, the use of a 9- or 10-gauge needle versus a 7- or 8-gauge needle was also an independently associated with underestimation when a diagnosis of ADH was made at MR imaging-guided biopsy. No other parameters were associated with of ADH or DCIS upgrade at surgery. Conclusion The rates of underestimation in ADH and DCIS diagnosed at MR imaging-guided vacuum-assisted biopsy were high, at around 25%, and were significantly associated with the presence of a mass at MR imaging. (c) RSNA, 2016. PMID- 27355899 TI - Effect of Time-of-Flight Information on PET/MR Reconstruction Artifacts: Comparison of Free-breathing versus Breath-hold MR-based Attenuation Correction. AB - Purpose To evaluate the magnitude and anatomic extent of the artifacts introduced on positron emission tomographic (PET)/magnetic resonance (MR) images by respiratory state mismatch in the attenuation map. Materials and Methods The method was tested on 14 patients referred for an oncologic examination who underwent PET/MR imaging. The acquisition included standard PET and MR series for each patient, and an additional attenuation correction series was acquired by using breath hold. PET data were reconstructed with and without time-of-flight (TOF) information, first by using the standard free-breathing attenuation map and then again by using the additional breath-hold map. Two-tailed paired t testing and linear regression with 0 intercept was performed on TOF versus non-TOF and free-breathing versus breath-hold data for all detected lesions. Results Fluorodeoxyglucose-avid lesions were found in eight of the 14 patients included in the study. The uptake differences (maximum standardized uptake values) between PET reconstructions with free-breathing versus breath-hold attenuation ranged, for non-TOF reconstructions, from -18% to 26%. The corresponding TOF reconstructions yielded differences from -15% to 18%. Conclusion TOF information was shown to reduce the artifacts caused at PET/MR by respiratory mismatch between emission and attenuation data. (c) RSNA, 2016 Online supplemental material is available for this article. PMID- 27355900 TI - Part II: new frontiers in antibacterial drug discovery. PMID- 27355901 TI - Site-dependent cobalt electronic state in La-Co co-substituted magnetoplumbite type ferrite: (59)Co nuclear magnetic resonance study. AB - The nuclear magnetic resonance of (59)Co was measured over a wide frequency range in a powder sample crushed from a well-characterized single crystal of La-Co co substituted magnetoplumbite-type strontium ferrite (SrFe12O19), a familiar base material for the ferrite permanent magnet. The simultaneous observation of both high- and low-frequency resonances suggests the coexistence of both high- and low spin states of the substituted Co or the presence of Co orbital moment at a particular site. The possible presence of trivalent Co was also investigated. The results suggest that the Co atoms are distributed across different crystallographic sites with different local environments, and that the electronic state of Co is much more subtle than the conventional understanding. PMID- 27355902 TI - Local Fine Structural Insight into Mechanism of Electrochemical Passivation of Titanium. AB - Electrochemically formed passive film on titanium in 1.0 M H2SO4 solution and its thickness, composition, chemical state, and local fine structure are examined by Auger electron spectroscopy (AES), X-ray photoelectron spectroscopy (XPS), and X ray absorption fine structure. AES analysis reveals that the thickness and composition of oxide film are proportional to the reciprocal of current density in potentiodynamic polarization. XPS depth profiles of the chemical states of titanium exhibit the coexistence of various valences cations in the surface. Quantitative X-ray absorption near edge structure analysis of the local electronic structure of the topmost surface (~5.0 nm) shows that the ratio of [TiO2]/[Ti2O3] is consistent with that of passivation/dissolution of electrochemical activity. Theoretical calculation and analysis of extended X-ray absorption fine structure spectra at Ti K-edge indicate that both the structures of passivation and dissolution are distorted caused by the appearance of two different sites of Ti-O and Ti-Ti. And the bound water in the topmost surface plays a vital role in structural disorder confirmed by XPS. Overall, the increase of average Ti-O coordination causes the electrochemical passivation, and the dissolution is due to the decrease of average Ti-Ti coordination. The structural variations of passivation in coordination number and interatomic distance are in good agreement with the prediction of point defect model. PMID- 27355903 TI - Modulation of cAMP levels by high-fat diet and curcumin and regulatory effects on CD36/FAT scavenger receptor/fatty acids transporter gene expression. AB - Curcumin, a polyphenol from turmeric (Curcuma longa), reduces inflammation, atherosclerosis, and obesity in several animal studies. In Ldlr-/- mice fed a high-fat diet (HFD), curcumin reduces plasma lipid levels, therefore contributing to a lower accumulation of lipids and to reduced expression of fatty acid transport proteins (CD36/FAT, FABP4/aP2) in peritoneal macrophages. In this study, we analyzed the molecular mechanisms by which curcumin (500, 1000, 1500 mg/kg diet, for 4 months) may influence plasma and tissue lipid levels in Ldlr-/- mice fed an HFD. In liver, HFD significantly suppressed cAMP levels, and curcumin restored almost normal levels. Similar trends were observed in adipose tissues, but not in brain, skeletal muscle, spleen, and kidney. Treatment with curcumin increased phosphorylation of CREB in liver, what may play a role in regulatory effects of curcumin in lipid homeostasis. In cell lines, curcumin increased the level of cAMP, activated the transcription factor CREB and the human CD36 promoter via a sequence containing a consensus CREB response element. Regulatory effects of HFD and Cur on gene expression were observed in liver, less in skeletal muscle and not in brain. Since the cAMP/protein kinase A (PKA)/CREB pathway plays an important role in lipid homeostasis, energy expenditure, and thermogenesis by increasing lipolysis and fatty acid beta-oxidation, an increase in cAMP levels induced by curcumin may contribute to its hypolipidemic and anti atherosclerotic effects. (c) 2016 BioFactors, 43(1):42-53, 2017. PMID- 27355905 TI - The evolving role of subspecialties in population health management and new healthcare delivery models. AB - New healthcare delivery models, including accountable care organizations (ACOs) and patient-centered medical homes, emphasize a more robust role for primary care. However, it is less clear how the roles and responsibilities of subspecialists should change as we enter a new paradigm of alternative payment models. Health systems seeking to better manage population health and control costs will need a clearer understanding of how best to incorporate subspecialty practitioners: What is a subspecialist's role? How does it vary by subspecialty? How should they be compensated? We argue that subspecialist compensation in ACOs and other new care delivery models should recognize the range of ways in which specialists can provide value to patients across a population-which varies depending on the provider's role in a patient's care. Only by more thoughtfully engaging, equipping, and compensating subspecialty practitioners can we achieve reform's central goal of better population health at a lower cost. PMID- 27355904 TI - Role of Heme Pocket Water in Allosteric Regulation of Ligand Reactivity in Human Hemoglobin. AB - Water molecules can enter the heme pockets of unliganded myoglobins and hemoglobins, hydrogen bond with the distal histidine, and introduce steric barriers to ligand binding. The spectrokinetics of photodissociated CO complexes of human hemoglobin and its isolated alpha and beta chains were analyzed for the effect of heme hydration on ligand rebinding. A strong coupling was observed between heme hydration and quaternary state. This coupling may contribute significantly to the 20-60-fold difference between the R- and T-state bimolecular CO binding rate constants and thus to the modulation of ligand reactivity that is the hallmark of hemoglobin allostery. Heme hydration proceeded over the course of several kinetic phases in the tetramer, including the R to T quaternary transition. An initial 150 ns hydration phase increased the R-state distal pocket water occupancy, nw(R), to a level similar to that of the isolated alpha (~60%) and beta (~10%) chains, resulting in a modest barrier to ligand binding. A subsequent phase, concurrent with the first step of the R -> T transition, further increased the level of heme hydration, increasing the barrier. The final phase, concurrent with the final step of the allosteric transition, brought the water occupancy of the T-state tetramer, nw(T), even higher and close to full occupancy in both the alpha and beta subunits (~90%). This hydration level could present an even larger barrier to ligand binding and contribute significantly to the lower iron reactivity of the T state toward CO. PMID- 27355906 TI - When doctors go to business school: career shoices of physician-MBAs. AB - There has been substantial growth in the number of physicians pursing Master of Business Administration (MBA) degrees over the past decade, but there is continuing debate over the utility of these programs and the career outcomes of their graduates. The authors analyzed the clinical and professional activities of a large cohort of physician-MBAs by gathering information on 206 physician graduates from the Harvard Business School MBA program who obtained their degrees between 1941 and 2014. Key outcome measures that were examined include medical specialty, current professional activity, and clinical practice. Chi square tests were used to assess the correlations in the data. Among the careers that were tracked (n = 195), there was significant heterogeneity in current primary employment. The most common sectors were clinical (27.7%), investment banking/finance (27.0%), hospital/provider administration (11.7%), biotech/device/pharmaceutical (10.9%), and entrepreneurship (9.5%). Overall, 84% of physician-MBAs entered residency; approximately half (49.3%) remained clinically active in some capacity and only one-fourth (27.7%) reported clinical medicine as their primary professional role. Among those who pursued residency training, the most common specialties were internal medicine (39.3%), emergency medicine (10.4%), orthopedic surgery (9.2%), and general surgery (8.6%). Physician-MBAs trained in internal medicine were significantly more likely to remain clinically active (63.8% vs 42.4%; P = .01). Clinical activity and primary employment in a clinical role decreased after degree conferment. After completing their education, a majority of physician-MBAs divert their primary professional focus away from clinical activity. These findings reveal new insights into the career outcomes of physician-MBAs. PMID- 27355907 TI - Value of improved lipid control in patients at high risk for adverse cardiac events. AB - OBJECTIVES: Lipid-lowering therapy (LLT) is suboptimally used in patients with hyperlipidemia in the 2 highest statin benefit groups (SBGs), as categorized by the American College of Cardiology and the American Heart Association. This study estimated the social value of reducing low-density lipoprotein cholesterol (LDL C) levels by 50% for patients in SBGs 1 and 2 who have been treated with standard LLT but have not reached LDL-C goal, as well as the potential value of PCSK9 inhibitors for patients in these groups. STUDY DESIGN: Simulation model. METHODS: We used National Health and Nutrition Examination Surveys (NHANES) and US Census data to project the population of SBGs 1 and 2 in the time period 2015 to 2035. We used insurance claims data to estimate incidence rates of major adverse cardiac events (MACEs), and NHANES with National Vital Statistics data to estimate cardiovascular disease mortality rates. Using established associations between LDL-C and MACE risk, we estimated the value of reducing LDL-C levels by 50%. We incorporated results from a meta-analysis to estimate the value of PSCK9 inhibitors. RESULTS: Among those treated with LLT with LDL-C > 70 mg/dL in SBGs 1 and 2, the cumulative value of reducing LDL-C levels by 50% would be $2.9 trillion from 2015 to 2035, resulting primarily from 1.6 million deaths averted. The cumulative value of PCSK9 inhibitors would range from $3.4 trillion to $5.1 trillion (1.9-2.8 million deaths averted), or $12,000 to $17,000 per patient-year of treatment. CONCLUSIONS: Lowering LDL-C in high-risk patients with hyperlipidemia has enormous potential social value. For patients in these high risk groups, PCSK9 inhibitors may have considerable net value depending on the final prices payers ultimately select. PMID- 27355908 TI - Review of outcomes associated with restricted access to atypical antipsychotics. AB - OBJECTIVES: Cost containment policies, such as prior authorization (PA), have increasingly been used by formulary decision makers to manage drug spending of the atypical antipsychotic (AAP) drug class. However, these drug cost containment policies may result in cost shifting rather than cost savings. Given the interest in coordination of care, the objective of this study was to evaluate the impact of restricted access to AAPs on healthcare costs and health outcomes in individuals with schizophrenia or bipolar disorder. STUDY DESIGN: Narrative literature review. METHODS: A literature search was conducted using MEDLINE (via PubMed) for studies published between January 1993 and December 2013. RESULTS: A total of 15 published studies were identified that evaluated restricted access to AAPs in regard to healthcare costs or health outcomes: 11 studies assessed PAs, 2 studies assessed carve-outs, 1 study assessed a payment limit (cap), and 1 study assessed Medicare Part D cost sharing. Among 8 studies evaluating changes in pharmacy costs and clinical outcomes, 5 studies reported that formulary restrictions were associated with pharmacy cost savings and increases in healthcare utilization or treatment discontinuation. Of the 4 studies that measured overall cost changes, 3 studies reported increases in overall cost burden and 1 study showed modest cost savings associated with formulary restrictions. CONCLUSIONS: Study findings revealed there exists a gap in the literature as to whether restricted access to AAPs results in overall cost savings or, rather, shifts the cost burden from pharmacy spending to other parts of the healthcare system, such as service utilization. PMID- 27355909 TI - Effects of physician payment reform on provision of home dialysis. AB - OBJECTIVES: Patients with end-stage renal disease can receive dialysis at home or in-center. In 2004, CMS reformed physician payment for in-center hemodialysis care from a capitated to a tiered fee-for-service model, augmenting physician payment for frequent in-center visits. We evaluated whether payment reform influenced dialysis modality assignment. STUDY DESIGN: Cohort study of patients starting dialysis in the United States in the 3 years before and the 3 years after payment reform. METHODS: We conducted difference-in-difference analyses comparing patients with traditional Medicare coverage (who were affected by the policy) to others with Medicare Advantage (who were unaffected by the policy). We also examined whether the policy had a more pronounced influence on dialysis modality assignment in areas with lower costs of traveling to dialysis facilities. RESULTS: Patients with traditional Medicare coverage experienced a 0.7% (95% CI, 0.2%-1.1%; P = .003) reduction in the absolute probability of home dialysis use following payment reform compared with patients with Medicare Advantage. Patients living in areas with larger dialysis facilities (where payment reform made in-center hemodialysis comparatively more lucrative for physicians) experienced a 0.9% (95% CI, 0.5%-1.4%; P < .001) reduction in home dialysis use following payment reform compared with patients living in areas with smaller facilities (where payment reform made in-center hemodialysis comparatively less lucrative for physicians). CONCLUSIONS: The transition from a capitated to a tiered fee-for-service payment model for in-center hemodialysis care resulted in fewer patients receiving home dialysis. This area of policy failure highlights the importance of considering unintended consequences of future physician payment reform efforts. PMID- 27355910 TI - Adoption of new agents and changes in treatment patterns for hepatitis C: 2010 2014. AB - OBJECTIVES: A number of new hepatitis C virus (HCV) medications have become available in the United States, but little is known about how these treatments have been adopted into practice and their financial burden on patients. The aim of this study was to examine whether the introduction of new HCV medications was associated with changes in treatment rates and out-of-pocket (OOP) costs. STUDY DESIGN: Retrospective analysis of administrative claims data from Optum Labs Data Warehouse. METHODS: We performed a retrospective analysis using a large, US commercial insurance database to identify 56,116 adults with chronic HCV between January 1, 2010, and December 31, 2014. Logistic regression was performed to calculate patients' predicted probability of being treated before and after the new medications became available. RESULTS: A total of 5436 (9.7%) of patients with HCV received treatment during an average of 1.8 years of follow-up. In the last quarter of 2014, 0.1% of patients with HCV received interferon/ribavirin as the primary treatment; no one received boceprevir or telaprevir, 1.1% received sofosbuvir combined with simeprevir, 1.4% received sofosbuvir or simeprevir alone, and 2.0% received ledipasvir/sofosbuvir. The introduction of new medications was significantly associated with an increased treatment rate, from 5.4% to 6.8% (P < .001). The increase was high among elderly patients and patients with liver transplant, liver cancer, and liver disease or cirrhosis. The median OOP costs of patients receiving new regimens were relatively low ($112 $340), but great variations existed. CONCLUSIONS: At the end of 2014, patients were almost exclusively using new therapies, which was associated with increased treatment rate, especially among patients who may need urgent treatment but are intolerant or ineligible for interferon-based regimens. PMID- 27355913 TI - Role of Diet in Inflammatory Bowel Disease. AB - The incidence of inflammatory bowel disease (IBD) is steadily in the rise in Western as well as in developing countries paralleling the increase of westernized diets, characterized by high protein and fat as well as excessive sugar intake, with less vegetables and fiber. An interesting hypothesis is that environmental (food-) triggered changes of the intestinal microbiome might cause a proinflammatory state preceding the development of IBD. Indeed, an intact intestinal epithelial barrier assuring a normal bacterial clearance of the intestinal surface is crucial to guarantee intestinal homeostasis. Any factors affecting the epithelial barrier function directly or indirectly may impact on this homeostasis, as well as any changes of the intestinal microbial composition. It is intriguing to learn that some frequently used food components impact on the quality of the intestinal barrier, as well as on the composition of the intestinal microbiome. This highlights the close interaction between living conditions, hygiene, food habits and food quality with the bacterial composition of the intestinal microbiome and the activation status of the intestinal immune system. There is clear evidence that nutritional therapy is highly successful in the treatment of Crohn's disease (CD). Exclusive enteral nutrition is well established as induction therapy of CD. New diets, such as a CD exclusion diet or defined diets (specific carbohydrate diets, FODMAP diet, Paleolithic diet) are being discussed as treatment options for IBD. Well-designed clinical trials in IBD are urgently required to define the precise role of each of these diets in the prevention or management of IBD. Up to now, the role of diet in IBD is highly undermined by lay and anecdotal reports without sufficient scientific proof. PMID- 27355912 TI - What has been learned from mouse models of the Fragile X Premutation and Fragile X-associated tremor/ataxia syndrome? AB - OBJECTIVE: To describe in this review how research using mouse models developed to study the Fragile X premutation (PM) and Fragile X-associated tremor/ataxia syndrome (FXTAS) have contributed to understanding these disorders. PM carriers bear an expanded CGG trinucleotide repeat on the Fragile X Mental Retardation 1 (FMR1) gene, and are at risk for developing the late onset neurodegenerative disorder FXTAS. CONCLUSIONS: Much has been learned about these genetic disorders from the development and study of mouse models. This includes new insights into the early cellular and molecular events that occur in PM carriers and in FXTAS, the presence of multiorgan pathology beyond the CNS, immunological dysregulation, unexpected synthesis of a potentially toxic peptide in FXTAS (i.e., FMRpolyG), and evidence that the disease process may be halted or reversed by appropriate molecular therapies given early in the course of disease. PMID- 27355911 TI - Nutritional supplements for people being treated for active tuberculosis. AB - BACKGROUND: Tuberculosis and malnutrition are linked in a complex relationship. Tuberculosis may cause undernutrition through increased metabolic demands and decreased intake, and nutritional deficiencies may worsen the disease, or delay recovery by depressing important immune functions. At present, there is no evidence-based nutritional guidance for adults and children being treated for tuberculosis. OBJECTIVES: To assess the effects of oral nutritional supplements in people being treated with antituberculous drug therapy for active tuberculosis. SEARCH METHODS: We searched the Cochrane Infectious Disease Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1, 2016), MEDLINE (from 1946 to 4 February 2016), EMBASE (from 1980 to 4 February 2016), LILACS (from 1982 to 4 February 2016), the metaRegister of Controlled Trials (mRCT), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and the Indian Journal of Tuberculosis up to 4 February 2016, and checked the reference lists of all included studies. SELECTION CRITERIA: Randomized controlled trials that compared any oral nutritional supplement given for at least four weeks with no nutritional intervention, placebo, or dietary advice only for people being treated for active tuberculosis. The primary outcomes of interest were all-cause death, and cure at six and 12 months. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, and extracted data and assessed the risk of bias in the included trials. We presented the results as risk ratios (RR) for dichotomous variables, and mean differences (MD) for continuous variables, with 95% confidence intervals (CIs). Where appropriate, we pooled data from trials with similar interventions and outcomes. We assessed the quality of the evidence using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Thirty-five trials, including 8283 participants, met the inclusion criteria of this review. Macronutrient supplementationSix trials assessed the provision of free food, or high-energy supplements. Only two trials measured total dietary intake, and in both trials the intervention increased calorie consumption compared to controls.The available trials were too small to reliably prove or exclude clinically important benefits on mortality (RR 0.34, 95% CI 0.10 to 1.20; four trials, 567 participants, very low quality evidence), cure (RR 0.91, 95% CI 0.59 to 1.41; one trial, 102 participants, very low quality evidence), or treatment completion (data not pooled; two trials, 365 participants, very low quality evidence).Supplementation probably produces a modest increase in weight gain during treatment for active tuberculosis, although this was not seen consistently across all trials (data not pooled; five trials, 883 participants, moderate quality evidence). Two small studies provide some evidence that quality of life may also be improved but the trials were too small to have much confidence in the result (data not pooled; two trials, 134 participants, low quality evidence). Micronutrient supplementationSix trials assessed multi-micronutrient supplementation in doses up to 10 times the dietary reference intake, and 18 trials assessed single or dual micronutrient supplementation.Routine multi-micronutrient supplementation may have little or no effect on mortality in HIV-negative people with tuberculosis (RR 0.86, 95% CI 0.46 to 1.6; four trials, 1219 participants, low quality evidence), or HIV positive people who are not taking antiretroviral therapy (RR 0.92, 95% CI 0.69 to 1.23; three trials, 1429 participants, moderate quality evidence). There is insufficient evidence to know if supplementation improves cure (no trials), treatment completion (RR 0.99, 95% CI 0.95 to 1.04; one trial, 302 participants, very low quality evidence), or the proportion of people who remain sputum positive during the first eight weeks (RR 0.92, 95% CI 0.63 to 1.35; two trials, 1020 participants, very low quality evidence). However, supplementation may have little or no effect on weight gain during treatment (data not pooled; five trials, 2940 participants, low quality evidence), and no studies have assessed the effect on quality of life.Plasma levels of vitamin A appear to increase following initiation of tuberculosis treatment regardless of supplementation. In contrast, supplementation probably does improve plasma levels of zinc, vitamin D, vitamin E, and selenium, but this has not been shown to have clinically important benefits. Of note, despite multiple studies of vitamin D supplementation in different doses, statistically significant benefits on sputum conversion have not been demonstrated. AUTHORS' CONCLUSIONS: There is currently insufficient research to know whether routinely providing free food, or energy supplements improves tuberculosis treatment outcomes, but it probably improves weight gain in some settings.Although blood levels of some vitamins may be low in people starting treatment for active tuberculosis, there is currently no reliable evidence that routinely supplementing above recommended daily amounts has clinical benefits. PMID- 27355915 TI - BF3.OEt2-mediated syn-selective Meyer-Schuster rearrangement of phenoxy propargyl alcohols for Z-beta-aryl-alpha,beta-unsaturated esters. AB - Synthesis of Z-beta-aryl-alpha,beta-unsaturated esters from readily available 1 aryl-3-phenoxy propargyl alcohols is achieved via a BF3-mediated syn-selective Meyer-Schuster rearrangement under ambient conditions. The reaction mechanism is postulated to involve an electrophilic borylation of an allene intermediate as the key step to kinetically control the stereoselectivity. PMID- 27355914 TI - Aggressive extensive cardiac mass in an HIV-1-infected patient: should we go for comfort therapy? AB - Cardiac masses are rare, the differential diagnosis includes infections with vegetations or abscesses, neoplasms, thrombi, and structural abnormalities. A pathology specimen is essential in therapeutic strategy planning for a cardiac mass, also if the primary imaging findings look dramatic at the start. Even in an inoperable setting, a life-saving therapy might be available. We report a case of a 49-year-old man, known with HIV-1, who was several times admitted with pericarditis. Now he was hospitalized with progressive lower limb edema, atrial fibrillation and detection of a giant cardiac mass in left and right atrium with infiltration of surrounding tissues. Given the extent and invasiveness of the mass, he was inoperable. Biopsy specimen was obtained and staging was performed by PET-CT scan. The diagnosis of stage IV Burkitt lymphoma with predominant extranodal cardiac involvement was withheld wherefore promptly aggressive therapy was started according to the GMALL B-NHL86 protocol. The therapy was downgraded to R-CHOP due to tolerance problems. He achieved a complete remission and during follow-up no relapse was detected. PMID- 27355916 TI - Identification and Characterization of IgE-Binding Tropomyosins in Aedes aegypti. AB - BACKGROUND: The mosquito Aedes aegypti is a potential source of important clinically relevant allergens. However, the allergenicity and cross-reactivity of most of these has not been fully described. METHODS: Natural wild-type mosquito tropomyosin was purified by size exclusion and anionic-exchange chromatography from an A. aegypti extract. Further characterization was accomplished by MALDI TOF/TOF. Two recombinant variants of tropomyosin were obtained by expression in Escherichia coli. Specific IgE measurement by ELISA and skin tests for mosquito extract were performed in 12 patients with asthma or allergy rhinitis residing on the Caribbean island of Martinique. Cross-reactivity between natural A. aegypti tropomyosin and recombinant tropomyosins from A. aegypti, house dust mite, shrimp and Ascaris lumbricoides was analyzed by ELISA competition. RESULTS: Four variants of natural tropomyosin were purified. A band of 32 kDa in SDS-PAGE representing 2 tropomyosin variants (Aed a 10.0101 and Aed a 10.0201) reacted with specific IgE of 4 of the 12 (33%) allergic patients and with rabbit polyclonal anti-shrimp tropomyosin. A high degree of cross-reactivity (60-70%) was detected between natural mosquito tropomyosin and Blo t 10, Der p 10 and Lit v 1, and a lower degree with Asc l 3 from A. lumbricoides (<30%). rAed a 10.0101 inhibited IgE binding to natural A. aegypti tropomyosin; however, rAed a 10.0201 showed a low inhibitory capacity. CONCLUSION: Tropomyosin is a new IgE-binding protein from A. aegypti. Two of the 4 variants identified showed different degree of cross-reactivity with tropomyosins from other arthropods. The potential allergenic role of each variant should be further investigated. PMID- 27355931 TI - Seroprevalence and Risk Factors of Varicella Zoster Infection in Iranian Adolescents: A Multilevel Analysis; The CASPIAN-III Study. AB - The objective of this study was to evaluate the varicella zoster virus (VZV) immunity in Iranian adolescents. It was conducted as a primary study for vaccine implementation, and to investigate the association of climatic and socioeconomic factors with the epidemiology of this infection. In this cross- sectional study, anti VZV antibodies were measured in serum samples obtained in a national school based health survey (CASPIAN- III). Association of demographic, socio-economic, and climate of the living region with the frequency of VZV was investigated by multivariate multilevel analysis. Overall, sera of 2753 individuals aged 10-18 were tested for VZV antibodies, from those 87.4% were positive. The prevalence was statistically different in four socio-geographic regions (P<0.001), varying between 85.24% in West region (mostly mountainous areas with cold climate) to 94.59% in Southeast region (subtropical climate). Among variables studied, only age and mean daily temperature of the living area were positively associated with the VZV seroprevalence. Our findings show that most Iranians develop immunity to VZV before the age of 10, but a substantial proportion of them are yet susceptible to the infection. Therefore, it seems that the best strategy to reduce the burden of the disease is to vaccinate high- risk adults, i.e. those without a history of varicella infection. The regional temperature might be the only determinant of VZV epidemiology in Iran. PMID- 27355932 TI - Anti-cancer effect of R3V6 peptide-mediated delivery of an anti-microRNA-21 antisense-oligodeoxynucleotide in a glioblastoma animal model. AB - MicroRNA-21 (miR-21) expression in glioblastoma inhibits the expression of pro apoptotic genes, thereby promoting tumor growth. A previous study showed that the amphiphilic R3V6 peptide is an efficient carrier of the anti-miR-21 antisense oligodeoxynucleotide (antisense-ODN) into cells in vitro. In the current study, in vivo delivery of antisense-ODN using the R3V6 peptide was evaluated in a glioblastoma animal model. In vitro transfection showed that the R3V6 peptide delivered antisense-ODN more efficiently than polyethylenimine (25 kDa, PEI25k) in C6 glioblastoma cells. For in vivo evaluation, antisense-ODN/R3V6 complex was injected intratumorally into a C6 glioblastoma xenograft animal model. Tumor growth was suppressed by the injection of the antisense-ODN/R3V6 complex, compared with the antisense-ODN/PEI25k and scrambled-antisense-ODN (scr-antisense ODN)/R3V6 complexes. Real-time RT-PCR showed that miR-21 levels were reduced most efficiently by the antisense-ODNR3V6 complex in tumors. Due to inhibition of miR 21, expression of the programed cell death 4 (PDCD4) gene was promoted in tumors, resulting in the induction of apoptosis of tumor cells. These results suggest that delivery of antisense-ODN using R3V6 peptides may be useful for the development of antisense-ODN therapy for glioblastoma. PMID- 27355933 TI - Streptococcus Gallolyticus Subsp. Pasteurianus Infection In A Neonatal Intensive Care Unit. AB - We report nosocomial transmission of Streptococcus gallolyticus subsp. pasteurianus among 3 neonates, 1 of whom died. Genome analysis of the strains showed a specific pattern of metabolic and regulatory functions as well as of expressed antigens and antibiotic resistance genes that might have contributed to their specific virulence. PMID- 27355934 TI - Differential Improvement of Executive Functions During Abstinence in Cocaine Dependent Patients: A Longitudinal Study. AB - BACKGROUND: In substance abusers, deficits in executive functioning (EF) are relevant to understanding the behavioral regulation of substance consumption and the failure to remain abstinent. OBJECTIVE: To determine the course of EF impairment, measured with traditional and ecological instruments, after 1 and 3 months of abstinence in patients with cocaine dependence. METHODS: 26 cocaine only-dependent in-patients (cocaine-dependent group, CDG) and 24 nondependent controls (control group, CG) recruited from a typical population were assessed using several EF tests and questionnaires [Stroop, verbal and graphic fluency, Wisconsin Card-Sorting Test (WCST), Tower of London (TOL), and Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)] after three periods of abstinence: 1 week, 1 month, and 3 months. RESULTS: At 1 week (baseline), CDG underperformed CG on most EF measures (WCST categories completed; TOL-total number of moves, execution time, and rule violations; and various BRIEF-A subscales). At 1 month, CDG moderately improved its performance on several measures, meanwhile the improvement in the 12 patients who would eventually complete the 3-month abstinence proved particularly significant when compared to their baseline values. In the a posteriori comparison of the baseline values of noncompleters versus completers, scores for the former were lower on the EF tasks, but higher on the BRIEF-A. Both groups, showed significantly worse scores than CG on both instruments. CONCLUSIONS/IMPORTANCE: Cocaine-dependent patients showed marked difficulties in the EF associated mainly with adaptive behavior to their environment. Cocaine-dependent patients with better EF at baseline improved significantly during abstinence and had better treatment adherence. Results suggest that executive improvement and treatment adherence in cocaine abusers in abstinence is related to intrinsic cognitive characteristics of patients. PMID- 27355935 TI - A One-Pot Tandem Strategy in Catalytic Asymmetric Vinylogous Aldol Reaction of Homoallylic Alcohols. AB - Reported is a rationally-designed one-pot sequential strategy that allows homoallylic alcohols to be employed in a catalytic, asymmetric, direct vinylogous aldol reaction with a series of activated acyclic ketones, including trifluoromethyl ketones, gamma-ketoesters, and alpha-keto phosphonates, in high yields (up to 95%) with excellent regio- and enantio-selectivity (up to 99% ee). This modular combination, including Jones oxidation and asymmetric organocatalysis, has satisfactory compatibility and reliability even at a 20 mmol scale, albeit without intermediary purification. PMID- 27355936 TI - Synthesis and Evaluation of Ciprofloxacin-Nitroxide Conjugates as Anti-Biofilm Agents. AB - As bacterial biofilms are often refractory to conventional antimicrobials, the need for alternative and/or novel strategies for the treatment of biofilm related infections has become of paramount importance. Herein, we report the synthesis of novel hybrid molecules comprised of two different hindered nitroxides linked to the piperazinyl secondary amine of ciprofloxacin via a tertiary amine linker achieved utilising reductive amination. The corresponding methoxyamine derivatives were prepared alongside their radical-containing counterparts as controls. Subsequent biological evaluation of the hybrid compounds on preformed P. aeruginosa flow cell biofilms divulged significant dispersal and eradication abilities for ciprofloxacin-nitroxide hybrid compound 10 (up to 95% eradication of mature biofilms at 40 MUM). Importantly, these hybrids represent the first dual-action antimicrobial-nitroxide agents, which harness the dispersal properties of the nitroxide moiety to circumvent the well-known resistance of biofilms to treatment with antimicrobial agents. PMID- 27355937 TI - Integrated Analysis of the Wood Oil from Xanthocyparis vietnamensis Farjon & Hiep. by Chromatographic and Spectroscopic Techniques. AB - In order to get better knowledge about the volatiles produced by Xanthocyparis vietnamensis, a species recently discovered in Vietnam, its wood oil has been analyzed by a combination of chromatographic (GC, CC) and spectroscopic (GC-MS, (13)C-NMR) techniques. Forty components that accounted for 87.9% of the oil composition have been identified. The composition is dominated by nootkatene (20.7%), 11,12,13-tri-nor-eremophil-1(10)-en-7-one (17.2%), gamma-eudesmol (5.1%), nootkatone (4.7%), valencene (3.5%) and 13-nor-eremophil-1(10)-en-11-one (2.6%). The structure of two new compounds-10-epi-nor-gamma-eudesmen-11-one and 12-hydroxy-isodihydroagarofuran-has been elucidated, while 11,12,13-tri-nor eremophil-1(10)-en-7-ol is reported as a natural product for the first time. The composition of X. vietnamensis wood oil varied drastically from those of leaf oils, dominated by hedycaryol (34.4%), phyllocladene (37.8%) or by pimara-6(14) 15-diene (19.4%). PMID- 27355938 TI - Chemical Synthesis of Deoxynivalenol-3-beta-d-[(13)C6]-glucoside and Application in Stable Isotope Dilution Assays. AB - Modified mycotoxins have been gaining importance in recent years and present a certain challenge in LC-MS/MS analysis. Due to the previous lack of a labeled isotopologue of the modified mycotoxin deoxynivalenol-3-glucoside, in our study we synthesized the first (13)C-labeled internal standard. Therefore, we used the Konigs-Knorr method to synthesize deoxynivalenol-3-beta-d-[(13)C6]-glucoside originated from unlabeled deoxynivalenol and [(13)C6]-labeled glucose. Using the synthesized isotopically-labeled standard deoxynivalenol-3-beta-d-[(13)C6] glucoside and the purchased labeled standard [(13)C15]-deoxynivalenol, a stable isotope dilution LC-MS/MS method was firstly developed for deoxynivalenol-3 glucoside and deoxynivalenol in beer. The preparation and purification of beer samples was based on a solid phase extraction. The validation data of the newly developed method gave satisfying results. Intra- and interday precision studies revealed relative standard deviations below 0.5% and 7%, respectively. The recoveries ranged for both analytes between 97% and 112%. The stable isotope dilution assay was applied to various beer samples from four different countries. In summary, deoxynivalenol-3-glucoside and deoxynivalenol mostly appeared together in varying molar ratios but were quantified in rather low contents in the investigated beers. PMID- 27355939 TI - Nanoparticles: Alternatives Against Drug-Resistant Pathogenic Microbes. AB - Antimicrobial substances may be synthetic, semisynthetic, or of natural origin (i.e., from plants and animals). Antimicrobials are considered "miracle drugs" and can determine if an infected patient/animal recovers or dies. However, the misuse of antimicrobials has led to the development of multi-drug-resistant bacteria, which is one of the greatest challenges for healthcare practitioners and is a significant global threat. The major concern with the development of antimicrobial resistance is the spread of resistant organisms. The replacement of conventional antimicrobials by new technology to counteract antimicrobial resistance is ongoing. Nanotechnology-driven innovations provide hope for patients and practitioners in overcoming the problem of drug resistance. Nanomaterials have tremendous potential in both the medical and veterinary fields. Several nanostructures comprising metallic particles have been developed to counteract microbial pathogens. The effectiveness of nanoparticles (NPs) depends on the interaction between the microorganism and the NPs. The development of effective nanomaterials requires in-depth knowledge of the physicochemical properties of NPs and the biological aspects of microorganisms. However, the risks associated with using NPs in healthcare need to be addressed. The present review highlights the antimicrobial effects of various nanomaterials and their potential advantages, drawbacks, or side effects. In addition, this comprehensive information may be useful in the discovery of broad-spectrum antimicrobial drugs for use against multi-drug-resistant microbial pathogens in the near future. PMID- 27355940 TI - Spectroscopic and Kinetic Characterization of Peroxidase-Like pi-Cation Radical Pinch-Porphyrin-Iron(III) Reaction Intermediate Models of Peroxidase Enzymes. AB - The spectroscopic and kinetic characterization of two intermediates from the H2O2 oxidation of three dimethyl ester [(proto), (meso), (deuteroporphyrinato) (picdien)]Fe(III) complexes ([FePPPic], [FeMPPic] and [FeDPPic], respectively) pinch-porphyrin peroxidase enzyme models, with s = 5/2 and 3/2 Fe(III) quantum mixed spin (qms) ground states is described herein. The kinetic study by UV/Vis at lambdamax = 465 nm showed two different types of kinetics during the oxidation process in the guaiacol test for peroxidases (1-3 + guaiacol + H2O2 -> oxidation guaiacol products). The first intermediate was observed during the first 24 s of the reaction. When the reaction conditions were changed to higher concentration of pinch-porphyrins and hydrogen peroxide only one type of kinetics was observed. Next, the reaction was performed only between pinch-porphyrins-Fe(III) and H2O2, resulting in only two types of kinetics that were developed during the first 0-4 s. After this time a self-oxidation process was observed. Our hypotheses state that the formation of the pi-cation radicals, reaction intermediates of the pinch porphyrin-Fe(III) family with the ligand picdien [N,N'-bis-pyridin-2-ylmethyl propane-1,3-diamine], occurred with unique kinetics that are different from the overall process and was involved in the oxidation pathway. UV-Vis, 1H-NMR and ESR spectra confirmed the formation of such intermediates. The results in this paper highlight the link between different spectroscopic techniques that positively depict the kinetic traits of artificial compounds with enzyme-like activity. PMID- 27355941 TI - Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells Characterization of a New in Vivo Model. AB - Chemoresistance and invasion properties are severe limitations to efficient glioma therapy. Therefore, development of glioma in vivo models that more accurately resemble the situation observed in patients emerges. Previously, we established RC6 rat glioma cell line resistant to DNA damaging agents including antiglioma approved therapies such as 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide (TMZ). Herein, we evaluated the invasiveness of RC6 cells in vitro and in a new orthotopic animal model. For comparison, we used C6 cells from which RC6 cells originated. Differences in cell growth properties were assessed by real-time cell analyzer. Cells' invasive potential in vitro was studied in fluorescently labeled gelatin and by formation of multicellular spheroids in hydrogel. For animal studies, fluorescently labeled cells were inoculated into adult male Wistar rat brains. Consecutive coronal and sagittal brain sections were analyzed 10 and 25 days post-inoculation, while rats' behavior was recorded during three days in the open field test starting from 25th day post-inoculation. We demonstrated that development of chemoresistance induced invasive phenotype of RC6 cells with significant behavioral impediments implying usefulness of orthotopic RC6 glioma allograft in preclinical studies for the examination of new approaches to counteract both chemoresistance and invasion of glioma cells. PMID- 27355942 TI - The X-ray Structures of Six Octameric RNA Duplexes in the Presence of Different Di- and Trivalent Cations. AB - Due to the polyanionic nature of RNA, the principles of charge neutralization and electrostatic condensation require that cations help to overcome the repulsive forces in order for RNA to adopt a three-dimensional structure. A precise structural knowledge of RNA-metal ion interactions is crucial to understand the mechanism of metal ions in the catalytic or regulatory activity of RNA. We solved the crystal structure of an octameric RNA duplex in the presence of the di- and trivalent metal ions Ca(2+), Mn(2+), Co(2+), Cu(2+), Sr(2+), and Tb(3+). The detailed investigation reveals a unique innersphere interaction to uracil and extends the knowledge of the influence of metal ions for conformational changes in RNA structure. Furthermore, we could demonstrate that an accurate localization of the metal ions in the X-ray structures require the consideration of several crystallographic and geometrical parameters as well as the anomalous difference map. PMID- 27355943 TI - Oenocarpus bacaba and Oenocarpus bataua Leaflets and Roots: A New Source of Antioxidant Compounds. AB - Native palm trees fruit from the Amazonian rainforest, Oenocarpus bacaba and Oenocarpus bataua, are very often used in the diet of local communities, but the biological activities of their roots and leaflets remain poorly known. Total phenolic content (TPC) and antioxidant activity of root and leaflet extracts from Oenocarpus bacaba and Oenocarpus bataua were assessed by using different chemical assays, the oxygen radical absorbance capacity (ORAC), the 2,2-diphenyl-l picrylhydrazyl (DPPH) free radical-scavenging capacity and the ferric-reducing ability of plasma (FRAP). Cellular antioxidant activity and cytotoxicity were also measured in Normal Human Dermal Fibroblasts. The polyphenolic composition of Oenocarpus extracts was investigated by LC-MS(n). Oenocarpus leaflet extracts were more antioxidant than root extracts, being at least as potent as Euterpe oleracea berries known as superfruit. Oenocarpus root extracts were characterized by hydroxycinnamic acids (caffeoylquinic and caffeoylshikimic acids), while leaflet extracts contained mainly caffeoylquinic acids and C-glycosyl flavones. These results suggest that leaflets of both Oenocarpus species could be valorized as a new non-cytotoxic source of antioxidants from Amazonia, containing hydroxycinnamic acids and flavonoids, in the pharmaceutical, cosmetic or agri food industry. PMID- 27355946 TI - Resolution-Enhanced Harmonic and Interharmonic Measurement for Power Quality Analysis in Cyber-Physical Energy System. AB - Power quality analysis issues, especially the measurement of harmonic and interharmonic in cyber-physical energy systems, are addressed in this paper. As new situations are introduced to the power system, the impact of electric vehicles, distributed generation and renewable energy has introduced extra demands to distributed sensors, waveform-level information and power quality data analytics. Harmonics and interharmonics, as the most significant disturbances, require carefully designed detection methods for an accurate measurement of electric loads whose information is crucial to subsequent analyzing and control. This paper gives a detailed description of the power quality analysis framework in networked environment and presents a fast and resolution-enhanced method for harmonic and interharmonic measurement. The proposed method first extracts harmonic and interharmonic components efficiently using the single-channel version of Robust Independent Component Analysis (RobustICA), then estimates the high-resolution frequency from three discrete Fourier transform (DFT) samples with little additional computation, and finally computes the amplitudes and phases with the adaptive linear neuron network. The experiments show that the proposed method is time-efficient and leads to a better accuracy of the simulated and experimental signals in the presence of noise and fundamental frequency deviation, thus providing a deeper insight into the (inter)harmonic sources or even the whole system. PMID- 27355945 TI - Screening of alpha-Tocopherol Transfer Protein Sensitive Genes in Human Hepatoma Cells (HepG2). AB - alpha-Tocopherol transfer protein (alpha-TTP) is a ~32 kDa protein expressed mainly in hepatocytes. The major function of the protein is to bind specifically to alpha-tocopherol and, together, the complex transfers from late lysosomes to the cell membrane. A previous study indicated that some factors might be required in the transferring process. However, there is little information available about the potential transferring factors. In addition, there remains much to learn about other physiological processes which alpha-TTP might participate in. Thus, in this study a human alpha-TTP eukaryotic expression vector was successfully constructed and expressed in human hepatoma cells (HepG2). The sensitive genes related to alpha-TTP were then screened by microarray technology. Results showed that expression of the vector in HepG2 cells led to the identification of 323 genes showing differential expression. The differentially expressed transcripts were divided into four main categories, including (1) cell inflammation; (2) cell cycle and cell apoptosis; (3) cell signaling and gene regulation; and (4) cellular movement. A few cellular movement related transcripts were selected and verified by quantitative real-time PCR. Expressions of some were significantly increased in alpha-TTP-expressed group, which indicated that these factors were likely to play a role in the transferring process. PMID- 27355947 TI - A Tightly-Coupled GPS/INS/UWB Cooperative Positioning Sensors System Supported by V2I Communication. AB - This paper investigates a tightly-coupled Global Position System (GPS)/Ultra Wideband (UWB)/Inertial Navigation System (INS) cooperative positioning scheme using a Robust Kalman Filter (RKF) supported by V2I communication. The scheme proposes a method that uses range measurements of UWB units transmitted among the terminals as augmentation inputs of the observations. The UWB range inputs are used to reform the GPS observation equations that consist of pseudo-range and Doppler measurements and the updated observation equation is processed in a tightly-coupled GPS/UWB/INS integrated positioning equation using an adaptive Robust Kalman Filter. The result of the trial conducted on the roof of the Nottingham Geospatial Institute (NGI) at the University of Nottingham shows that the integrated solution provides better accuracy and improves the availability of the system in GPS denied environments. RKF can eliminate the effects of gross errors. Additionally, the internal and external reliabilities of the system are enhanced when the UWB observables received from the moving terminals are involved in the positioning algorithm. PMID- 27355948 TI - Source Anonymity in WSNs against Global Adversary Utilizing Low Transmission Rates with Delay Constraints. AB - Wireless sensor networks (WSN) are deployed for many applications such as tracking and monitoring of endangered species, military applications, etc. which require anonymity of the origin, known as Source Location Privacy (SLP). The aim in SLP is to prevent unauthorized observers from tracing the source of a real event by analyzing the traffic in the network. Previous approaches to SLP such as Fortified Anonymous Communication Protocol (FACP) employ transmission of real or fake packets in every time slot, which is inefficient. To overcome this shortcoming, we developed three different techniques presented in this paper. Dummy Uniform Distribution (DUD), Dummy Adaptive Distribution (DAD) and Controlled Dummy Adaptive Distribution (CAD) were developed to overcome the anonymity problem against a global adversary (which has the capability of analyzing and monitoring the entire network). Most of the current techniques try to prevent the adversary from perceiving the location and time of the real event whereas our proposed techniques confuse the adversary about the existence of the real event by introducing low rate fake messages, which subsequently lead to location and time privacy. Simulation results demonstrate that the proposed techniques provide reasonable delivery ratio, delay, and overhead of a real event's packets while keeping a high level of anonymity. Three different analysis models are conducted to verify the performance of our techniques. A visualization of the simulation data is performed to confirm anonymity. Further, neural network models are developed to ensure that the introduced techniques preserve SLP. Finally, a steganography model based on probability is implemented to prove the anonymity of the techniques. PMID- 27355950 TI - A MAC Protocol to Support Monitoring of Underwater Spaces. AB - Underwater sensor networks are becoming an important field of research, because of their everyday increasing application scope. Examples of their application areas are environmental and pollution monitoring (mainly oil spills), oceanographic data collection, support for submarine geolocalization, ocean sampling and early tsunamis alert. The challenge of performing underwater communications is well known, provided that radio signals are useless in this medium, and a wired solution is too expensive. Therefore, the sensors in these networks transmit their information using acoustic signals that propagate well under water. This data transmission type not only brings an opportunity, but also several challenges to the implementation of these networks, e.g., in terms of energy consumption, data transmission and signal interference. In order to help advance the knowledge in the design and implementation of these networks for monitoring underwater spaces, this paper proposes a MAC protocol for acoustic communications between the nodes, based on a self-organized time division multiple access mechanism. The proposal was evaluated using simulations of a real monitoring scenario, and the obtained results are highly encouraging. PMID- 27355949 TI - Verification of Geometric Model-Based Plant Phenotyping Methods for Studies of Xerophytic Plants. AB - This paper presents the results of verification of certain non-contact measurement methods of plant scanning to estimate morphological parameters such as length, width, area, volume of leaves and/or stems on the basis of computer models. The best results in reproducing the shape of scanned objects up to 50 cm in height were obtained with the structured-light DAVID Laserscanner. The optimal triangle mesh resolution for scanned surfaces was determined with the measurement error taken into account. The research suggests that measuring morphological parameters from computer models can supplement or even replace phenotyping with classic methods. Calculating precise values of area and volume makes determination of the S/V (surface/volume) ratio for cacti and other succulents possible, whereas for classic methods the result is an approximation only. In addition, the possibility of scanning and measuring plant species which differ in morphology was investigated. PMID- 27355951 TI - Sensor Network-Based and User-Friendly User Location Discovery for Future Smart Homes. AB - User location is crucial context information for future smart homes where many location based services will be proposed. This location necessarily means that User Location Discovery (ULD) will play an important role in future smart homes. Concerns about privacy and the need to carry a mobile or a tag device within a smart home currently make conventional ULD systems uncomfortable for users. Future smart homes will need a ULD system to consider these challenges. This paper addresses the design of such a ULD system for context-aware services in future smart homes stressing the following challenges: (i) users' privacy; (ii) device-/tag-free; and (iii) fault tolerance and accuracy. On the other hand, emerging new technologies, such as the Internet of Things, embedded systems, intelligent devices and machine-to-machine communication, are penetrating into our daily life with more and more sensors available for use in our homes. Considering this opportunity, we propose a ULD system that is capitalizing on the prevalence of sensors for the home while satisfying the aforementioned challenges. The proposed sensor network-based and user-friendly ULD system relies on different types of inexpensive sensors, as well as a context broker with a fuzzy-based decision-maker. The context broker receives context information from different types of sensors and evaluates that data using the fuzzy set theory. We demonstrate the performance of the proposed system by illustrating a use case, utilizing both an analytical model and simulation. PMID- 27355952 TI - Time and Energy Efficient Relay Transmission for Multi-Hop Wireless Sensor Networks. AB - The IEEE 802.15.4 standard is widely recognized as one of the most successful enabling technologies for short range low rate wireless communications and it is used in IoT applications. It covers all the details related to the MAC and PHY layers of the IoT protocol stack. Due to the nature of IoT, the wireless sensor networks are autonomously self-organized networks without infrastructure support. One of the issues in IoT is the network scalability. To address this issue, it is necessary to support the multi-hop topology. The IEEE 802.15.4 network can support a star, peer-to-peer, or cluster-tree topology. One of the IEEE 802.15.4 topologies suited for the high predictability of performance guarantees and energy efficient behavior is a cluster-tree topology where sensor nodes can switch off their transceivers and go into a sleep state to save energy. However, the IEEE 802.15.4 cluster-tree topology may not be able to provide sufficient bandwidth for the increased traffic load and the additional information may not be delivered successfully. The common drawback of the existing approaches is that they do not address the poor bandwidth utilization problem in IEEE 802.15.4 cluster-tree networks, so it is difficult to increase the network performance. Therefore, to solve this problem in this paper we study a relay transmission protocol based on the standard protocol in the IEEE 802.15.4 MAC. In the proposed scheme, the coordinators can relay data frames to their parent devices or their children devices without contention and can provide bandwidth for the increased traffic load or the number of devices. We also evaluate the performance of the proposed scheme through simulation. The simulation results demonstrate that the proposed scheme can improve the reliability, the end-to-end delay, and the energy consumption. PMID- 27355953 TI - A Flexible Optical pH Sensor Based on Polysulfone Membranes Coated with pH Responsive Polyaniline Nanofibers. AB - A new optical pH sensor based on polysulfone (PSU) and polyaniline (PANI) was developed. A transparent and flexible PSU membrane was employed as a support. The electrically conductive and pH-responsive PANI was deposited onto the membrane surface by in situ chemical oxidative polymerization (COP). The absorption spectra of the PANI-coated PSU membranes exhibited sensitivity to pH changes in the range of 4-12, which allowed for designing a dual wavelength pH optical sensor. The performance of the membranes was assessed by measuring their response starting from high pH and going down to low pH, and vice versa. It was found that it is necessary to precondition the sensor layers before each measurement due to the slight hysteresis observed during forward and backward pH titrations. PSU membranes with polyaniline coating thicknesses in the range of ~100-200 nm exhibited fast response times of <4 s, which are attributed to the porous, rough and nanofibrillar morphology of the polyaniline coating. The fabricated pH sensor was characterized by a sigmoidal response (R2 = 0.997) which allows for pH determination over a wide dynamic range. All membranes were stable for a period of more than six months when stored in 1 M HCl solution. The reproducibility of the fabricated optical pH sensors was found to be <0.02 absorption units after one month storage in 1 M HCl solution. The performance of the optical pH sensor was tested and the obtained pH values were compared with the results obtained using a pH meter device. PMID- 27355954 TI - Design of Miniaturized Dual-Band Microstrip Antenna for WLAN Application. AB - Wireless local area network (WLAN) is a technology that combines computer network with wireless communication technology. The 2.4 GHz and 5 GHz frequency bands in the Industrial Scientific Medical (ISM) band can be used in the WLAN environment. Because of the development of wireless communication technology and the use of the frequency bands without the need for authorization, the application of WLAN is becoming more and more extensive. As the key part of the WLAN system, the antenna must also be adapted to the development of WLAN communication technology. This paper designs two new dual-frequency microstrip antennas with the use of electromagnetic simulation software-High Frequency Structure Simulator (HFSS). The two antennas adopt ordinary FR4 material as a dielectric substrate, with the advantages of low cost and small size. The first antenna adopts microstrip line feeding, and the antenna radiation patch is composed of a folded T-shaped radiating dipole which reduces the antenna size, and two symmetrical rectangular patches located on both sides of the T-shaped radiating patch. The second antenna is a microstrip patch antenna fed by coaxial line, and the size of the antenna is diminished by opening a stepped groove on the two edges of the patch and a folded slot inside the patch. Simulation experiments prove that the two designed antennas have a higher gain and a favourable transmission characteristic in the working frequency range, which is in accordance with the requirements of WLAN communication. PMID- 27355955 TI - On Curating Multimodal Sensory Data for Health and Wellness Platforms. AB - In recent years, the focus of healthcare and wellness technologies has shown a significant shift towards personal vital signs devices. The technology has evolved from smartphone-based wellness applications to fitness bands and smartwatches. The novelty of these devices is the accumulation of activity data as their users go about their daily life routine. However, these implementations are device specific and lack the ability to incorporate multimodal data sources. Data accumulated in their usage does not offer rich contextual information that is adequate for providing a holistic view of a user's lifelog. As a result, making decisions and generating recommendations based on this data are single dimensional. In this paper, we present our Data Curation Framework (DCF) which is device independent and accumulates a user's sensory data from multimodal data sources in real time. DCF curates the context of this accumulated data over the user's lifelog. DCF provides rule-based anomaly detection over this context-rich lifelog in real time. To provide computation and persistence over the large volume of sensory data, DCF utilizes the distributed and ubiquitous environment of the cloud platform. DCF has been evaluated for its performance, correctness, ability to detect complex anomalies, and management support for a large volume of sensory data. PMID- 27355956 TI - A Bandwidth-Efficient Dissemination Scheme of Non-Safety Information in Urban VANETs. AB - The recent release of standards for vehicular communications will hasten the development of smart cities in the following years. Many applications for vehicular networks, such as blocked road warnings or advertising, will require multi-hop dissemination of information to all vehicles in a region of interest. However, these networks present special features and difficulties that may require special measures. The dissemination of information may cause broadcast storms. Urban scenarios are especially sensitive to broadcast storms because of the high density of vehicles in downtown areas. They also present numerous crossroads and signal blocking due to buildings, which make dissemination more difficult than in open, almost straight interurban roadways. In this article, we discuss several options to avoid the broadcast storm problem while trying to achieve the maximum coverage of the region of interest. Specifically, we evaluate through simulations different ways to detect and take advantage of intersections and a strategy based on store-carry-forward to overcome short disconnections between groups of vehicles. Our conclusions are varied, and we propose two different solutions, depending on the requirements of the application. PMID- 27355957 TI - Link Investigation of IEEE 802.15.4 Wireless Sensor Networks in Forests. AB - Wireless sensor networks are expected to automatically monitor the ecological evolution and wildlife habits in forests. Low-power links (transceivers) are often adopted in wireless sensor network applications, in order to save the precious sensor energy and then achieve long-term, unattended monitoring. Recent research has presented some performance characteristics of such low-power wireless links under laboratory or outdoor scenarios with less obstacles, and they have found that low-power wireless links are unreliable and prone to be affected by the target environment. However, there is still less understanding about how well the low-power wireless link performs in real-world forests and to what extent the complex in-forest surrounding environments affect the link performances. In this paper, we empirically evaluate the low-power links of wireless sensors in three typical different forest environments. Our experiment investigates the performance of the link layer compatible with the IEEE 802.15.4 standard and analyzes the variation patterns of the packet reception ratio (PRR), the received signal strength indicator (RSSI) and the link quality indicator (LQI) under diverse experimental settings. Some observations of this study are inconsistent with or even contradict prior results that are achieved in open fields or relatively clean environments and thus, provide new insights both into effectively evaluating the low-power wireless links and into efficiently deploying wireless sensor network systems in forest environments. PMID- 27355958 TI - Announcing the 2016 Pharmaceuticals Travel Award for Young Investigators. AB - For the first time in its short history, our journal is able, this year, to support a young researcher in the field of medicinal chemistry by offering a travel grant of 800 CHF.[...]. PMID- 27355944 TI - Mesenchymal Stem and Progenitor Cells in Normal and Dysplastic Hematopoiesis Masters of Survival and Clonality? AB - Myelodysplastic syndromes (MDS) are malignant hematopoietic stem cell disorders that have the capacity to progress to acute myeloid leukemia (AML). Accumulating evidence suggests that the altered bone marrow (BM) microenvironment in general, and in particular the components of the stem cell niche, including mesenchymal stem cells (MSCs) and their progeny, play a pivotal role in the evolution and propagation of MDS. We here present an overview of the role of MSCs in the pathogenesis of MDS, with emphasis on cellular interactions in the BM microenvironment and related stem cell niche concepts. MSCs have potent immunomodulatory capacities and communicate with diverse immune cells, but also interact with various other cellular components of the microenvironment as well as with normal and leukemic stem and progenitor cells. Moreover, compared to normal MSCs, MSCs in MDS and AML often exhibit altered gene expression profiles, an aberrant phenotype, and abnormal functional properties. These alterations supposedly contribute to the "reprogramming" of the stem cell niche into a disease-permissive microenvironment where an altered immune system, abnormal stem cell niche interactions, and an impaired growth control lead to disease progression. The current article also reviews molecular targets that play a role in such cellular interactions and possibilities to interfere with abnormal stem cell niche interactions by using specific targeted drugs. PMID- 27355959 TI - Site-Specific Labeling of Protein Kinase CK2: Combining Surface Display and Click Chemistry for Drug Discovery Applications. AB - Human CK2 is a heterotetrameric constitutively active serine/threonine protein kinase and is an emerging target in current anti-cancer drug discovery. The kinase is composed of two catalytic CK2alpha subunits and two regulatory CK2beta subunits. In order to establish an assay to identify protein-protein-interaction inhibitors (PPI) of the CK2alpha/CK2beta interface, a bioorthogonal click reaction was used to modify the protein kinase alpha-subunit with a fluorophore. By expanding the genetic code, the unnatural amino acid para azidophenylalanine (pAzF) could be incorporated into CK2alpha. Performing the SPAAC click reaction (Strain-Promoted Azide-Alkyne Cycloaddition) by the use of a dibenzylcyclooctyne fluorophore (DBCO-fluorophore) led to a specifically labeled human protein kinase CK2alpha. This site-specific labeling does not impair the phosphorylation activity of CK2, which was evaluated by capillary electrophoresis. Furthermore a dissociation constant (KD) of 631 +/- 86.2 nM was determined for the substrate alphaS1-casein towards CK2alpha. This labeling strategy was also applied to CK2beta subunit on Escherichia coli, indicating the site-specific modifications of proteins on the bacterial cell surface when displayed by Autodisplay. PMID- 27355960 TI - Pretrichodermamides D-F from a Marine Algicolous Fungus Penicillium sp. KMM 4672. AB - Three new epidithiodiketopiperazines pretrichodermamides D-F (1-3), together with the known N-methylpretrichodermamide B (4) and pretrichodermamide S (5), were isolated from the lipophilic extract of the marine algae-derived fungus Penicillium sp. KMM 4672. The structures of compounds 1-5 were determined based on spectroscopic methods. The absolute configuration of pretrichodermamide D (1) was established by a combination of modified Mosher's method, NOESY data, and biogenetic considerations. N-Methylpretrichodermamide B (5) showed strong cytotoxicity against 22Rv1 human prostate cancer cells resistant to androgen receptor targeted therapies. PMID- 27355962 TI - The Life-Cycle Costs of School Water, Sanitation and Hygiene Access in Kenyan Primary Schools. AB - Water, Sanitation and Hygiene (WASH) programs in schools can increase the health, dignity and comfort of students and teachers. Understanding the costs of WASH facilities and services in schools is one essential piece for policy makers to utilize when budgeting for schools and helping to make WASH programs more sustainable. In this study we collected data from NGO and government offices, local hardware shops and 89 rural primary schools across three Kenyan counties. Current expenditures on WASH, from school and external (NGO, government, parent) sources, averaged 1.83 USD per student per year. After reviewing current expenditures, estimated costs of operations and maintenance for bringing schools up to basic WASH standards, were calculated to be 3.03 USD per student per year. This includes recurrent costs, but not the cost of installing or setting up WASH infrastructure, which was 18,916 USD per school, for a school of 400 students (4.92 USD per student, per year). These findings demonstrate the need for increases in allocations to schools in Kenya, and stricter guidance on how money should be spent on WASH inputs to enable all schools to provide basic WASH for all students. PMID- 27355961 TI - The Relationship between C-Reactive Protein Level and Discharge Outcome in Patients with Acute Ischemic Stroke. AB - Previous studies showed that C-reactive protein (CRP), an inflammatory marker, was associated with stroke severity and long-term outcome. However, the relationship between the acute-phase CRP level and discharge outcome has received little attention. We prospectively studied 301 patients with acute ischemic stroke (over a period of two weeks) from two hospital stroke wards and one rehabilitation department in Henan, China. Patients' demographic and clinical data were collected and evaluated at admission. Poor discharge outcome was assessed in patients at discharge using the Modified Rankin Scale (MRS > 2). Multivariate logistic regression analysis was performed to determine the risk factors of poor discharge outcome after adjusting for potential confounders. Poor discharge outcome was observed in 78 patients (25.9%). Univariate analyses showed that factors significantly influencing poor discharge outcome were age, residence, recurrent acute ischemic stroke, coronary heart disease, the National Institutes of Health Stroke Scale (NIHSS) score at admission, non-lacunar stroke, time from onset of stroke to admission, CRP, TBIL (total bilirubin), direct bilirubin (DBIL), ALB (albumin), FIB (fibrinogen) and D-dimer (p < 0.05). After adjusting for age, residence, recurrent ischemic stroke, coronary heart disease, NIHSS score at admission, lacunar stroke, time from onset of stroke to admission, CRP, TBIL, DBIL, ALB, FIB and D-dimer, multivariate logistic regression analyses revealed that poor outcome at discharge was associated with recurrent acute ischemic stroke (OR, 2.115; 95% CI, 1.094-4.087), non-lacunar stroke (OR, 2.943; 95% CI, 1.436-6.032), DBIL (OR, 1.795; 95% CI, 1.311-2.458), and CRP (OR, 4.890; 95% CI, 3.063-7.808). In conclusion, the CRP level measured at admission was found to be an independent predictor of poor outcome at discharge. Recurrent acute ischemic stroke, non-lacunar stroke and DBIL were also significantly associated with discharge outcome in acute ischemic stroke. PMID- 27355963 TI - Novel Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Oral Delivery of Olmesartan Medoxomil: Design, Formulation, Pharmacokinetic and Bioavailability Evaluation. AB - The main purpose of this study was to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) of Olmesartan (OLM) for enhancement of its solubility and dissolution rate. In this study, liquid SNEDDS containing Olmesartan was formulated and further developed into a solid form by the spray drying technique using Aerosil 200 as a solid carrier. Based on the preliminary screening of different unloaded SNEDDS formulae, eight formulae of OLM loaded SNEEDS were prepared using Capryol 90, Cremophor RH40 and Transcutol HP as oil, surfactant and cosurfactant, respectively. Results showed that the mean droplet size of all reconstituted SNEDDS was found to be in the nanometric range (14.91-22.97 nm) with optimum PDI values (0.036-0.241). All formulae also showed rapid emulsification time (15.46 +/- 1.34-24.17 +/- 1.47 s), good optical clarity (98.33% +/- 0.16%-99.87% +/- 0.31%) and high drug loading efficiency (96.41% +/- 1.20%-99.65% +/- 1.11%). TEM analysis revealed the formation of spherical and homogeneous droplets with a size smaller than 50 nm. In vitro release of OLM from SNEDDS formulae showed that more than 90% of OLM released in approximately 90 min. Optimized SNEDDS formulae were selected to be developed into S-SNEDDS using the spray drying technique. The prepared S-SNEDDS formulae were evaluated for flow properties, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), reconstitution properties, drug content and in vitro dissolution study. It was found that S-SNEDDS formulae showed good flow properties and high drug content. Reconstitution properties of S-SNEDDS showed spontaneous self-nanoemulsification and no sign of phase separation. DSC thermograms revealed that OLM was in solubilized form and FTIR supported these findings. SEM photographs showed smooth uniform surface of S-SNEDDS with less aggregation. Results of the in vitro drug release showed that there was great enhancement in the dissolution rate of OLM. To clarify the possible improvement in pharmacokinetic behavior of OLM S-SNEDDS, plasma concentration-time curve profiles of OLM after the oral administration of optimized S-SNEDDS formula (F3) were compared to marketed product and pure drug in suspension. At all time points, it was observed that OLM plasma concentrations in rats treated with S SNEDDS were significantly higher than those treated with the drug in suspension and marketed product. PMID- 27355964 TI - Wnt Signaling in Cancer Stem Cell Biology. AB - Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer. PMID- 27355967 TI - Improved Manufacturing Performance of Screen Printed Carbon Electrodes through Material Formulation. AB - Printed carbon graphite materials are the primary common component in the majority of screen printed sensors. Screen printing allows a scalable manufacturing solution, accelerating the means by which novel sensing materials can make the transition from laboratory material to commercial product. A common bottleneck in any thick film printing process is the controlled drying of the carbon paste material. A study has been undertaken which examines the interaction between material solvent, printed film conductivity and process consistency. The study illustrates that it is possible to reduce the solvent boiling point to significantly increase process productivity while maintaining process consistency. The lower boiling point solvent also has a beneficial effect on the conductivity of the film, reducing the sheet resistance. It is proposed that this is a result of greater film stressing increasing charge percolation through greater inter particle contact. Simulations of material performance and drying illustrate that a multi layered printing provides a more time efficient manufacturing method. The findings have implications for the volume manufacturing of the carbon sensor electrodes but also have implications for other applications where conductive carbon is used, such as electrical circuits and photovoltaic devices. PMID- 27355966 TI - The Sound of Vision Project: On the Feasibility of an Audio-Haptic Representation of the Environment, for the Visually Impaired. AB - The Sound of Vision project involves developing a sensory substitution device that is aimed at creating and conveying a rich auditory representation of the surrounding environment to the visually impaired. However, the feasibility of such an approach is strongly constrained by neural flexibility, possibilities of sensory substitution and adaptation to changed sensory input. We review evidence for such flexibility from various perspectives. We discuss neuroplasticity of the adult brain with an emphasis on functional changes in the visually impaired compared to sighted people. We discuss effects of adaptation on brain activity, in particular short-term and long-term effects of repeated exposure to particular stimuli. We then discuss evidence for sensory substitution such as Sound of Vision involves, while finally discussing evidence for adaptation to changes in the auditory environment. We conclude that sensory substitution enterprises such as Sound of Vision are quite feasible in light of the available evidence, which is encouraging regarding such projects. PMID- 27355969 TI - Friedrich Loffler Prize: D. Segets / Toray Science and Technology Prize: S. Kobayashi / Inhoffen Medal: T. Carell / Leipzig Science Prize: A. G. Beck Sickinger / Nenitzescu-Criegee Lectureship: E. Hey-Hawkins / Humboldt, Siemens, and Bessel Research Awards / New Members of German Academies of Sciences and Humanities. PMID- 27355968 TI - Physician Assimilation in Medical Schools: Dualisms of Biomedical and Biopsychosocial Ideologies in the Discourse of Physician Educators. AB - Although health communication research and popular literature on physicians have heightened awareness of the dualisms physicians face, research is yet to focus on the discourse of physician educators who assimilate students into medicine for dualisms of the biomedical (BMD) and biopsychosocial (BPS) ideologies. The study drew on a dualism-centered model to analyze the discourse of 19 behavioral science course directors at 10 medical schools for the emergence of dualisms in instantiations of BPS ideologies and for the management of dualism in discourse that instantiated both BMD and BPS ideologies as part of the curriculum. Dualism emerged in the BPS ideologies of "patient-centeredness" and "cultural competence." While a dualism between "patients' data" and "patients' stories" emerged in the patient-centeredness ideology, a dualism between enhancing "interaction skill" and "understanding" emerged in the cultural competence ideology. Moreover, the study found educator discourse managing dualism between BMD and BPS ideologies through the strategies of "connection" and "separation." The study concludes with a discussion and the implications for theory and research. PMID- 27355965 TI - Epithelial Intermediate Filaments: Guardians against Microbial Infection? AB - Intermediate filaments are abundant cytoskeletal components of epithelial tissues. They have been implicated in overall stress protection. A hitherto poorly investigated area of research is the function of intermediate filaments as a barrier to microbial infection. This review summarizes the accumulating knowledge about this interaction. It first emphasizes the unique spatial organization of the keratin intermediate filament cytoskeleton in different epithelial tissues to protect the organism against microbial insults. We then present examples of direct interaction between viral, bacterial, and parasitic proteins and the intermediate filament system and describe how this affects the microbe-host interaction by modulating the epithelial cytoskeleton, the progression of infection, and host response. These observations not only provide novel insights into the dynamics and function of intermediate filaments but also indicate future avenues to combat microbial infection. PMID- 27355970 TI - Surprisingly Different Reaction Behavior of Alkali and Alkaline Earth Metal Bis(trimethylsilyl)amides toward Bulky N-(2-Pyridylethyl)-N'-(2,6 diisopropylphenyl)pivalamidine. AB - N-(2,6-Diisopropylphenyl)-N'-(2-pyridylethyl)pivalamidine (Dipp-N=C(tBu)-N(H)-C2 H4 -Py) (1), reacts with metalation reagents of lithium, magnesium, calcium, and strontium to give the corresponding pivalamidinates [(tmeda)Li{Dipp-N=C(tBu)-N-C2 H4 -Py}] (6), [Mg{Dipp-N=C(tBu)-N-C2 H4 -Py}2 ] (3), and heteroleptic [{(Me3 Si)2 N}Ae{Dipp-N=C(tBu)-N-C2 H4 -Py}], with Ae being Ca (2 a) and Sr (2 b). In contrast to this straightforward deprotonation of the amidine units, the reaction of 1 with the bis(trimethylsilyl)amides of sodium or potassium unexpectedly leads to a beta-metalation and an immediate deamidation reaction yielding [(thf)2 Na{Dipp-N=C(tBu)-N(H)}] (4 a) or [(thf)2 K{Dipp-N=C(tBu)-N(H)}] (4 b), respectively, as well as 2-vinylpyridine in both cases. The lithium derivative shows a similar reaction behavior to the alkaline earth metal congeners, underlining the diagonal relationship in the periodic table. Protonation of 4 a or the metathesis reaction of 4 b with CaI2 in tetrahydrofuran yields N-(2,6 diisopropylphenyl)pivalamidine (Dipp-N=C(tBu)-NH2 ) (5), or [(thf)4 Ca{Dipp N=C(tBu)-N(H)}2 ] (7), respectively. The reaction of AN(SiMe3 )2 (A=Na, K) with less bulky formamidine Dipp-N=C(H)-N(H)-C2 H4 -Py (8) leads to deprotonation of the amidine functionality, and [(thf)Na{Dipp-N=C(H)-N-C2 H4 -Py}]2 (9 a) or [(thf)K{Dipp-N=C(H)-N-C2 H4 -Py}]2 (9 b), respectively, are isolated as dinuclear complexes. From these experiments it is obvious, that beta-metalation/deamidation of N-(2-pyridylethyl)amidines requires bases with soft metal ions and also steric pressure. The isomeric forms of all compounds are verified by single-crystal X ray structure analysis and are maintained in solution. PMID- 27355971 TI - Metal-Semiconductor Nanoparticle Hybrids Formed by Self-Organization: A Platform to Address Exciton-Plasmon Coupling. AB - Hybrid nanosystems composed of excitonic and plasmonic constituents can have different properties than the sum of of the two constituents, due to the exciton plasmon interaction. Here, we report on a flexible model system based on colloidal nanoparticles that can form hybrid combinations by self-organization. The system allows us to tune the interparticle distance and to combine nanoparticles of different sizes and thus enables a systematic investigation of the exciton-plasmon coupling by a combination of optical spectroscopy and quantum optical theory. We experimentally observe a strong influence of the energy difference between exciton and plasmon, as well as an interplay of nanoparticle size and distance on the coupling. We develop a full quantum theory for the luminescence dynamics and discuss the experimental results in terms of the Purcell effect. As the theory describes excitation as well as coherent and incoherent emission, we also consider possible quantum optical effects. We find a good agreement of the observed and the calculated luminescence dynamics induced by the Purcell effect. This also suggests that the self-organized hybrid system can be used as platform to address quantum optical effects. PMID- 27355972 TI - Your Loved One Has Migraines. PMID- 27355973 TI - Protodeboronation of Heteroaromatic, Vinyl, and Cyclopropyl Boronic Acids: pH Rate Profiles, Autocatalysis, and Disproportionation. AB - pH-rate profiles for aqueous-organic protodeboronation of 18 boronic acids, many widely viewed as unstable, have been studied by NMR and DFT. Rates were pH dependent, and varied substantially between the boronic acids, with rate maxima that varied over 6 orders of magnitude. A mechanistic model containing five general pathways (k1-k5) has been developed, and together with input of [B]tot, KW, Ka, and KaH, the protodeboronation kinetics can be correlated as a function of pH (1-13) for all 18 species. Cyclopropyl and vinyl boronic acids undergo very slow protodeboronation, as do 3- and 4-pyridyl boronic acids (t0.5 > 1 week, pH 12, 70 degrees C). In contrast, 2-pyridyl and 5-thiazolyl boronic acids undergo rapid protodeboronation (t0.5 ~ 25-50 s, pH 7, 70 degrees C), via fragmentation of zwitterionic intermediates. Lewis acid additives (e.g., Cu, Zn salts) can attenuate (2-pyridyl) or accelerate (5-thiazolyl and 5-pyrazolyl) fragmentation. Two additional processes compete when the boronic acid and the boronate are present in sufficient proportions (pH = pKa +/- 1.6): (i) self-/autocatalysis and (ii) sequential disproportionations of boronic acid to borinic acid and borane. PMID- 27355974 TI - Discovery and Pharmacokinetic and Pharmacological Properties of the Potent and Selective MET Kinase Inhibitor 1-{6-[6-(4-Fluorophenyl)-[1,2,4]triazolo[4,3 b]pyridazin-3-ylsulfanyl]benzothiazol-2-yl}-3-(2-morpholin-4-ylethyl)urea (SAR125844). AB - The HGF/MET pathway is frequently activated in a variety of cancer types. Several selective small molecule inhibitors of the MET kinase are currently in clinical evaluation, in particular for NSCLC, liver, and gastric cancer patients. We report herein the discovery of a series of triazolopyridazines that are selective inhibitors of wild-type (WT) MET kinase and several clinically relevant mutants. We provide insight into their mode of binding and report unprecedented crystal structures of the Y1230H variant. A multiparametric chemical optimization approach allowed the identification of compound 12 (SAR125844) as a development candidate. In this chemical series, absence of CYP3A4 inhibition was obtained at the expense of satisfactory oral absorption. Compound 12, a promising parenteral agent for the treatment of MET-dependent cancers, promoted sustained target engagement at tolerated doses in a human xenograft tumor model. Preclinical pharmacokinetics conducted in several species were predictive for the observed pharmacokinetic behavior of 12 in cancer patients. PMID- 27355975 TI - Macrocephaly and palmoplantar pitting. PMID- 27355976 TI - Red blood cell distribution width predicts prognosis in idiopathic sudden sensorineural hearing loss. AB - CONCLUSION: Red cell distribution width (RDW) can predict outcome in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). Further studies are required to clarify the potential pathophysiological explanations for these findings. OBJECTIVES: RDW is one of the parameters reported in a complete blood count, and is elevated in direct proportion to variation in red cell size (anisocytosis). High RDW values are strongly associated with poor clinical outcomes in various diseases, including inflammatory and thrombotic diseases. To identify a prognostic biomarker that better predicts outcomes after ISSNHL, the association between RDW values at hospitalization and prognosis in patients with ISSNHL was assessed. METHOD: This study measured RDW and performed hearing assessments in 89 consecutive patients with ISSNHL. Patients were then divided into two groups ('recovered' and 'unrecovered'), according to their response to the treatment, and further analysis undertaken. RESULTS: Mean RDW was significantly higher in the unrecovered group (13.2% +/- 1.0% compared with 12.7% +/- 0.7% in the recovered group, p = 0.031). After adjusting for potentially confounding factors in a binary logistic regression model, only RDW was associated with recovery from ISSNHL (odds ratio = 2.33, 95% confidence interval = 1.20-4.51, p = 0.012). PMID- 27355977 TI - Dynamic Percolation and Swollen Behavior of Nanodroplets in 1-Ethyl-3 methylimidazolium Trifluoromethanesulfonate/Triton X-100/Cyclohexane Microemulsions. AB - Microemulsions comprising an ionic liquid (IL), 1-ethyl-3-methylimidazolium trifluoromethanesulfonate ([emim][OTf]), as the polar component, Triton X-100 as a surfactant, and cyclohexane as the nonpolar medium were prepared and characterized. Conductivity and dynamic viscosity data were critically analyzed to confirm dynamic percolation among the droplets that are in continuous motion, aggregation, and fission. The transition from oil-continuous phase to bicontinuous phase was observed at the conductance and viscosity percolation thresholds and sharp changes in the values of conductivity and dynamic viscosity could be identified. Dynamic light scattering measurements revealed swelling of the droplets, which varied within the hydrodynamic diameter range of 10-100 nm. Diffusivity of the droplets suggested less Brownian movement with increased amount of the IL. Moreover, changes in the droplet sizes and diffusivity with increase in IL content supported dynamic percolation within the systems. PMID- 27355980 TI - Gestational Weight Gain: Association with Adverse Pregnancy Outcomes. AB - Background It is unclear how adherence to the Institute of Medicine's (IOM) guidelines for weight gain affects pregnancy outcomes. Objective We investigated how weight gain outside the IOM's recommendations affects the risks of adverse pregnancy outcomes. Study Design We performed a secondary analysis of a prospective cohort study including singleton, nonanomalous fetuses. The risks of small for gestational age (SGA), macrosomia, preeclampsia, cesarean delivery, gestational diabetes, or preterm birth were calculated for patients who gained weight below or above the IOM's recommendations based on body mass index category. A time-to-event analysis was performed to account for gestational age at delivery. A Cox proportional model was fit to estimate hazard ratios accounting for possible confounders. Results Women who gained weight below recommendations were 2.5 times more likely to deliver SGA and twice as likely to deliver preterm. Normal-weight patients who gained below recommendations were 2.5 times more likely to deliver SGA and twice as likely to deliver preterm. Obese patients who gained inadequate weight were 2.5 times more likely to deliver SGA. Conclusion Among normal-weight patients, adhering to IOM recommendations may prevent growth abnormalities and preterm delivery. Among obese patients, a minimum weight gain requirement may prevent SGA infants. PMID- 27355981 TI - A rare case of an androgen-producing stromal luteoma of the ovary in a postmenopausal woman, diagnosed by means of selective venous blood sampling. PMID- 27355979 TI - Retrospective Analysis of an Interdisciplinary Ventilator Care Program Intervention on Survival of Infants with Ventilator-Dependent Bronchopulmonary Dysplasia. AB - Background The clinical needs of infants with severe bronchopulmonary dysplasia (BPD) that remain ventilator-dependent are complex, and management strategies that optimize survival and long-term outcomes controversial. We hypothesized that an interdisciplinary ventilator care program (VCP), committed to the care of this population will improve survival through standardized approaches to cardiopulmonary care and related comorbidities, enhanced communication, and continuity of care. Methods Retrospective chart reviews were performed on patients at Children's Hospital Colorado's neonatal intensive care unit, who underwent tracheostomy placement between 2000 and 2013. Data were collected for two time periods: 2000 to 2005 and 2006 to 2013, before and after initiation of the VCP. Collected data on infants with ventilator-dependent BPD included: gestational age (GA), age at tracheostomy, respiratory severity score (RSS; mean airway pressure [MAP] * fraction of inspired oxygen [FiO2]), comorbidities, medication use, and the age of death. Tracheostomy patients without severe BPD were excluded. Results Despite no difference in GA, birth weight, or cardiorespiratory comorbidities, survival to discharge increased from 50 to 85% after implementation of the VCP (p < 0.05). Between period 1 and 2, there were differences in systemic and inhaled steroid use and mucolytic use. Conclusion These findings suggest an interdisciplinary approach to the care of infants with ventilator-dependent BPD can improve survival. PMID- 27355982 TI - Benthic macroinvertebrate community in the Sinos river drainage basin, Rio Grande do Sul, Brazil. AB - Aquatic macroinvertebrate fauna is a relevant component of limnic continental aquatic ecosystems, playing an important role in several processes with relevant biocomplexity. The present study characterized the benthic macroinvertebrate fauna found in three hydric bodies in the Sinos river drainage basin regarding community structure. Sample was collected from January to December 2013 in three locations in the basin: the city of Caraa (29 degrees 45'45.5"S/50 degrees 19'37.3"W), the city of Rolante (29 degrees 38'34.4"S/50 degrees 32'33.2"W) and the city of Igrejinha (29 degrees 36'10.84"S/50 degrees 48'49.3"W). Abiotic components (pH, dissolved oxygen and temperature) were registered and collected samples were identified up to family type. Average annual pH, dissolved oxygen and temperature were similar in all locations. A total of 26,170 samples were collected. Class Insecta (Arthropods) represented 85.5% of total sample. Platyhelmintes, Mollusca and Annelida samples were also registered. A total of 57 families were identified for the drainage basin and estimators (Chao-1, Chao-2 and jackknife 2) estimated richness varying from 60 to 72 families. PMID- 27355983 TI - Distribution and conservation of three important bird groups of the Atlantic Forest in north-east Brazil. AB - The Pernambuco Endemism Center in north-east Brazil has the most fragmented forest cover and the largest number of threatened birds of the whole Atlantic Forest. We analyzed the distribution of three groups of bird species: forest dependent, endemic and/or threatened using the interpolation method of Inverse Distance Weighting. We also checked the concentration of these birds in protected and unprotected areas, suggesting new sites that need to be protected. The richness concentration of forest-dependent, endemic and/or threatened birds in 123 sites were analysed. There was a greater concentration of the three groups in north Alagoas, south and north Pernambuco, and north and west Paraiba. The distribution of the three groups was almost regular in different vegetation types, although a lower concentration was found in the pioneer formation. There was a greater concentration of birds from all three groups between Pernambuco and Alagoas, and this must be due to the presence of more forest fragments with better structure and vegetation heterogeneity. The protected and unprotected areas hosted important records of endemic and/or threatened birds. We suggested some important places for implementation of new protected areas due to the larger concentrations of the target birds and because they are located within the boundaries of the Important Bird Areas. PMID- 27355984 TI - Can We Detect Transfusion Benefits in Palliative Care Patients? AB - BACKGROUND: Red blood cell (RBC) transfusions are commonly prescribed for palliative care patients for symptoms. However, RBCs are a limited resource, transfusion is not without risk, and may be of variable benefit in people approaching the end of life. The aim of this study was to review RBC transfusions in our palliative care unit (PCU), examining evidence of benefit or harms, and preparing for a prospective multisite study. METHODS: This consecutive cohort study retrospectively reviewed transfusions administered during a PCU admission. Hemoglobin levels, physical function, and symptom rating for breathing and fatigue (Symptom Assessment Scale) were assessed before transfusion, and at days 2 and 7. RESULTS: Thirty-one patients received 44 transfusions over the two-year period. Of these patients, the average age was 64 years and 45% were male. Eighty nine percent of transfusions were thought to be of subjective benefit by clinicians, and 94% of patients reported symptomatic improvement. However, overall, there was little change in scale-based measures of physical function or symptoms, with response rates <25% in all scales. No predictors of response were found considering pretransfusion hemoglobin, hemoglobin increment, Australia modified Karnofsky Performance Status, or discharge status. Deterioration after transfusion was prevalent. CONCLUSION: For RBC transfusion in palliative care patients, the majority had subjective benefit. However, subjective improvement correlated poorly with objective scale-based measures. The sensitivity of assessment scales, high rates of placebo response, and the multifactorial nature of symptoms at the end of life make evaluation of RBC transfusions challenging. PMID- 27355985 TI - What Determines the Ice Polymorph in Clouds? AB - Ice crystals in the atmosphere nucleate from supercooled liquid water and grow by vapor uptake. The structure of the ice polymorph grown has strong impact on the morphology and light scattering of the ice crystals, modulates the amount of water vapor in ice clouds, and can impact the molecular uptake and reactivity of atmospheric aerosols. Experiments and molecular simulations indicate that ice nucleated and grown from deeply supercooled liquid water is metastable stacking disordered ice. The ice polymorph grown from vapor has not yet been determined. Here we use large-scale molecular simulations to determine the structure of ice that grows as a result of uptake of water vapor in the temperature range relevant to cirrus and mixed-phase clouds, elucidate the molecular mechanism of the formation of ice at the vapor interface, and compute the free energy difference between cubic and hexagonal ice interfaces with vapor. We find that vapor deposition results in growth of stacking disordered ice only under conditions of extreme supersaturation, for which a nonequilibrium liquid layer completely wets the surface of ice. Such extreme conditions have been used to produce stacking disordered frost ice in experiments and may be plausible in the summer polar mesosphere. Growth of ice from vapor at moderate supersaturations in the temperature range relevant to cirrus and mixed-phase clouds, from 200 to 260 K, produces exclusively the stable hexagonal ice polymorph. Cubic ice is disfavored with respect to hexagonal ice not only by a small penalty in the bulk free energy (3.6 +/- 1.5 J mol(-1) at 260 K) but also by a large free energy penalty at the ice-vapor interface (89.7 +/- 12.8 J mol(-1) at 260 K). The latter originates in higher vibrational entropy of the hexagonal-terminated ice-vapor interface. We predict that the free energy penalty against the cubic ice interface should decrease strongly with temperature, resulting in some degree of stacking disorder in ice grown from vapor in the tropical tropopause layer, and in polar stratospheric and noctilucent clouds. Our findings support and explain the evolution of the morphology of ice crystals from hexagonal to trigonal symmetry with decreasing temperature, as reported by experiments and in situ measurements in clouds. We conclude that selective growth of the elusive cubic ice polymorph by manipulation of the interfacial properties can likely be achieved at the ice liquid interface but not at the ice-vapor interface. PMID- 27355986 TI - Greatly Accelerated Condensation of d-Mannose Diacetonide with Aqueous Formaldehyde (Formalin). AB - Condensation of d-mannose diacetate with aqueous formaldehyde, a long known quaternary center-generating transformation, was reinvestigated to solve the hidden problem of incomplete conversion, a lasting challenge since 1979 despite many previous efforts. The mysterious cause for the retarded transformation was found to be generation of formic acid by a Cannizzaro reaction. By using additional amounts of base, the reaction time was shortened from 48 h to 100 min and the product was readily isolated in 81% yield. PMID- 27355987 TI - Di- versus Trinuclear Copper(II) Cryptate for the Uptake of Dicarboxylate Anions. AB - Searching for receptors selective for the binding of dicarboxylate anions, the copper(II) complexes of the known ditopic octaazacryptand (t2pN8), derived from bistren [tren = tris(2-aminoethyl)amine] linked by p-xylyl spacers, were re examined, with the expectation of observing a selective binding of oxalate or malonate by bridging the two copper centers of the [Cu2(t2pN8)(H2O)2](4+) receptor. Solution studies involving the supramolecular species formed by the receptor and oxalate (oxa(2-)), malonate (mal(2-)), and succinate (suc(2-)) anions are reported. The determined association constants revealed the unexpected formation of a 3:1:1 Cu/t2pN8/anion stoichiometry for the cascade species with oxa(2-) and mal(2-), and the single crystal X-ray structural characterization confirmed the presence of tricopper(II) complexes, with an unusual binding mode for the dicarboxylate anions. Each of the two copper atoms binds four nitrogen donor atoms of the t2pN8 cryptand and one additional hydroxide group, which bridges to the third copper. The square planar environment of this one is complete with two oxygen atoms from the oxalate (or the malonate). The two copper centers bound to the tren heads are ~6.5 A apart, each one at about 3.5 A from the third Cu center. These studies were complemented by SQUID magnetization measurements and DFT calculations. The magnetic susceptibility measurements of the oxalate cascade complex showed a strong magnetic coupling (J = - 210 cm(-1)) between the Cu centers at a short distance (3.5 A), while the coupling between the two equivalent Cu atoms (~6.5 A) was only -70 cm(-1). This result was well reproduced by DFT calculations. PMID- 27355988 TI - Unexpected effect of tetraglyme plasticizer on lithium ion dynamics in PAMPS based ionomers. AB - Li(+) cation conducting ionomers based on poly(2-acrylamido-2-methyl-1-propane sulphonic acid) (PAMPS) incorporating a low molecular weight plasticizer have been characterized. Previously we have observed an apparent decoupling of ionic conductivity and lithium ion dynamics from the Tg of this ionomer along with an increase in ionic conductivity obtained by incorporating a quaternary ammonium co cation. The incorporation of tetraglyme as a coordinating plasticizer was investigated in order to further improve the ion dissociation and dynamics. Solid state NMR, thermal analysis, impedance spectroscopy and infrared spectroscopy were used to characterize these systems. As expected, the glass transition temperature Tg decreased upon the addition of the plasticizer. However, in contrast to the previously reported Na-conducting systems, the ionic conductivity was also decreased by several orders of magnitude, indicating that the tetraglyme recouples the conductivity back to the polymer dynamics. Temperature dependent (7)Li NMR line width and T1 measurements were used to probe the Li(+) dynamics, which were found to be dependent on the Li(+) concentration, the nature of the co cation and the presence or absence of tetraglyme. PMID- 27355989 TI - HfMnSb2 : A Metal-Ordered NiAs-type Pnictide with a Conical Spin Order. AB - The NiAs-type structure is one of the most common structures in solids, but metal order has been almost exclusively limited to chalcogenides. The synthesis of HfMnSb2 is reported with a novel metal-ordered NiAs-type structure. HfMnSb2 undergoes a conical spin order below 270 K, in marked contrast to conventional magnetic order observed in NiAs-type pnictides. We argue that the layered arrangement of Hf and Mn makes it a quasi 2D magnet, where the Mn layers with localized magnetic moments (Mn(2+) ; S=5/2) can interact only through RKKY interactions, instead of metal-metal bonding that is otherwise dominant for typical NiAs-type pnictides. This result suggests that controlling order-disorder in NiAs-type pnictides enables a study of 2D-to-3D crossover behavior in itinerant magnetic system. PMID- 27355994 TI - Challenges of antihypertensive treatment. PMID- 27355995 TI - Treatment of hypertension and the price to pay; adverse events and discontinuation from randomized treatment in clinical trials. PMID- 27355996 TI - Endothelial dysfunction in hypertension: achievements and open questions. PMID- 27355997 TI - Home blood pressure and treatment decisions: caveat emptor. PMID- 27355990 TI - Nutritional strategies to optimise cognitive function in the aging brain. AB - Old age is the greatest risk factor for most neurodegenerative diseases. During recent decades there have been major advances in understanding the biology of aging, and the development of nutritional interventions that delay aging including calorie restriction (CR) and intermittent fasting (IF), and chemicals that influence pathways linking nutrition and aging processes. CR influences brain aging in many animal models and recent findings suggest that dietary interventions can influence brain health and dementia in older humans. The role of individual macronutrients in brain aging also has been studied, with conflicting results about the effects of dietary protein and carbohydrates. A new approach known as the Geometric Framework (GF) has been used to unravel the complex interactions between macronutrients (protein, fat, and carbohydrate) and total energy on outcomes such as aging. These studies have shown that low protein, high-carbohydrate (LPHC) diets are optimal for lifespan in ad libitum fed animals, while total calories have minimal effect once macronutrients are taken into account. One of the primary purposes of this review is to explore the notion that macronutrients may have a more translational potential than CR and IF in humans, and therefore there is a pressing need to use GF to study the impact of diet on brain aging. Furthermore, given the growing recognition of the role of aging biology in dementia, such studies might provide a new approach for dietary interventions for optimizing brain health and preventing dementia in older people. PMID- 27355998 TI - Central versus peripheral blood pressure: finding a solution. PMID- 27355999 TI - Amiloride and the diabetic kidney. PMID- 27356000 TI - Device-based treatments in hypertension: think physiology. PMID- 27356001 TI - Renal denervation for resistant hypertension: closing in on potential confounders. PMID- 27356002 TI - AT1-pathway inhibition in aneurysm growth and cardiac failure. PMID- 27356003 TI - Reply. PMID- 27356005 TI - Reply. PMID- 27356004 TI - Is white-coat hypertension associated with increased cardiovascular and mortality risk? PMID- 27356006 TI - Influence of Various Living Donor Kidney Measurements in Relation to Recipient Body Measurements on Posttransplant Allograft Functional Outcomes. AB - OBJECTIVES: Donor kidney measurements may affect outcomes of transplanted allografts. We tested allograft and recipient measurements on kidney allograft outcomes. In this study, we compared the effects of kidney allograft volumes, which were measured using computed tomographic angiography before transplant, and allograft weight, which was measured during surgery, in relation to the recipient's body weight and body mass index on kidney function at 6 and 12 months after transplant. MATERIAL AND METHODS: We included 74 patients (40 female and 34 male patients, mean age of 50.42 +/- 9.75 y) in this study. RESULTS: Intraoperative allograft weight was 182.68 +/- 40.33 g (range, 104-266 g). The allograft volume measured using computed tomographic angiography scanning was 123.34 +/- 24.26 mL (range, 78-181 mL). The estimated glomerular filtration rates of the recipients at 6 and 12 months after transplant correlated negatively with age and recipient body mass index but correlated positively with allograft volume/recipient body weight, allograft volume/recipient body mass index, allograft weight, allograft weight/recipient body weight, and allograft weight/recipient body mass index values, as concluded by univariate analyses. From multivariate analyses, we found variables of interest presumed to significantly affect the 12-month estimated glomerular filtration rates, including recipient age, allograft volume/recipient body weight, allograft volume/recipient body mass index, allograft weight, allograft weight/recipient body weight, and allograft weight/recipient body mass index. CONCLUSIONS: Transplanted allograft and recipient body values may be used as predictors of estimated glomerular filtration rates 6 and 12 months after transplant. PMID- 27356007 TI - Truths, Myths and Needs of Special Diets: Attention-Deficit/Hyperactivity Disorder, Autism, Non-Celiac Gluten Sensitivity, and Vegetarianism. AB - Different dietary approaches have been attempted for the treatment of attention deficit/hyperactivity disorder and autism, but only three of them have been subjected to clinical trials: education in healthy nutritional habits, supplementation and elimination diets. On the other hand, for multiple reasons, the number of people who adopt vegetarian and gluten-free diets (GFD) increases daily. More recently, a new entity, non-celiac gluten sensitivity (NCGS), with a still evolving definition and clinical spectrum, has been described. Although, the benefits of GFD are clearly supported in this condition as well as in celiac disease, in the last two decades, GFD has expanded to a wider population. In this review, we will attempt to clarify, according to the existing evidence, which are the myths and facts of these diets. PMID- 27356008 TI - Association of Anterior Cruciate Ligament Width With Anterior Knee Laxity. AB - CONTEXT: Greater anterior knee laxity (AKL) has been identified as an anterior cruciate ligament (ACL) injury risk factor. The structural factors that contribute to greater AKL are not fully understood but may include the ACL and bone geometry. OBJECTIVE: To determine the relationship of ACL width and femoral notch angle to AKL. DESIGN: Cross-sectional study. SETTING: Controlled laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty recreationally active females (age = 21.2 +/- 3.1 years, height = 1.66.1 +/- 7.3 cm, mass = 66.5 +/- 12.0 kg). MAIN OUTCOME MEASURE(S): Anterior cruciate ligament width and femoral notch angle were obtained with magnetic resonance imaging of the knee and AKL was assessed. Anterior cruciate ligament width was measured as the width of a line that transected the ACL and was drawn perpendicular to the Blumensaat line. Femoral notch angle was formed by the intersection of the line parallel to the posterior cortex of the femur and the Blumensaat line. Anterior knee laxity was the anterior displacement of the tibia relative to the femur (mm) at 130 N of an applied force. Ten participants' magnetic resonance imaging data were assessed on 2 occasions to establish intratester reliability and precision. Using stepwise backward linear regression, we examined the extent to which ACL width, femoral notch angle, and weight were associated with AKL. RESULTS: Strong measurement consistency and precision (intraclass correlation coefficient [2,1] +/- SEM) were established for ACL width (0.98 +/- 0.3 mm) and femoral notch angle (0.97 degrees +/- 1.1 degrees ). The regression demonstrated that ACL width (5.9 +/- 1.4 mm) was negatively associated with AKL (7.2 +/- 2.0 mm; R(2) = 0.22, P = .04). Femoral notch angle and weight were not retained in the final model. CONCLUSIONS: A narrower ACL was associated with greater AKL. This finding may inform the development of ACL injury-prevention programs that include components designed to increase ACL size or strength (or both). Future authors should establish which other factors contribute to greater AKL in order to best inform injury-prevention efforts. PMID- 27356009 TI - Biomechanical study of distal radioulnar joint ballottement test. AB - We investigated the reliability and accuracy of the distal radioulnar joint (DRUJ) ballottement test using five fresh-frozen cadaver specimens in triangular fibrocartilage complex (TFCC)-intact, and TFCC-sectioned wrists. The humerus and proximal ulna were fixed. The ulna was allowed to translate in dorsopalmar directions without rotation, and the radius was allowed to move freely. Four sensors of a magnetic tracking system were attached to the radius and ulna, and the nails of each examiner's thumbs. Five examiners conducted the DRUJ ballottement test before and after TFCC sectioning. We used two techniques: With holding and without holding the carpal bones to the radius (holding and non holding tests, respectively). We compared the magnitudes of bone-to-bone (absolute DRUJ) movement with that of the examiner's nail-to-nail (relative DRUJ) movement. The intrarater intraclass correlation coefficients (ICCs) were 0.92 (holding) and 0.94 (non-holding). The interrater ICCs were 0.84 (holding) and 0.75 (non-holding). Magnitudes of absolute and relative movements averaged 11.5 and 11.8 mm, respectively (p < 0.05). Before TFCC sectioning, the DRUJ movement during the holding and non-holding techniques averaged 9.8 and 10.8 mm, respectively (p < 0.05). The increase in DRUJ movement after TFCC sectioning was greater with the holding technique (average 2.3 mm) than with the non-holding technique (average 1.6 mm). The DRUJ ballottement test with magnetic markers is relatively accurate and reliable for detecting unstable joints. We recommend the holding technique for assessing DRUJ instability in clinical practice. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1123-1127, 2017. PMID- 27356010 TI - Estimation and Preparation of the Hypervariable Regions I/II Templates for Mitochondrial DNA Typing From Human Bones and Teeth Remains Using Singleplex Quantitative Polymerase Chain Reaction. AB - A method was designed for estimating and sequencing of mitochondrial DNA (mtDNA) that effectively and more quickly provides a complete mtDNA profile. In this context, we have developed this novel strategy for typing mtDNA from 10 bones and teeth remains (3 months to 44 years). The quantification of mtDNA was achieved by singleplex real-time polymerase chain reaction of the hypervariable region I fragment (445 bp) and hypervariable region II fragment (617 bp). Combined with the melting curve analysis, we have determined as little as 10 pg of mtDNA template that is suitable for sequence analysis. Furthermore, quantitative polymerase chain reaction products were directly used for following step of mtDNA typing by Sanger sequencing. This method allows the profile to be completely provided for faster human identification. PMID- 27356011 TI - Gastric Mucosal Petechial Hemorrhages (Wischnewsky Lesions), Hypothermia, and Diabetic Ketoacidosis. AB - For more than 100 years since their initial description, gastric mucosal petechial hemorrhages have been discovered at autopsy in cases where environmental hypothermia was determined to be the cause of death. Although these lesions are frequently seen in deaths caused by environmental hypothermia, they can also be seen in cases where hypothermia is not implicated; however, this has been seldom described. We present a series of autopsy cases where hypothermia has been conclusively ruled out as a cause of death, in which Wischnewsky lesions are found. In all of these cases, diabetic ketoacidosis (DKA) was determined to be the proximate cause of death, as confirmed through clinical history, laboratory analysis, and absence of other anatomic or toxicological findings. We provide a mechanism of Wischnewsky lesion formation and how that mechanism relates to both hypothermia and ketoacidosis. Our data show that gastric mucosal petechial hemorrhages are not specific for hypothermia-related deaths, and are likely indicative of a state in which hypothermia and DKA have a common underlying pathophysiology, most likely a coagulopathy. Our data also illustrate that in autopsy cases where Wischnewsky lesions are found, DKA should be seriously considered as the underlying cause of death, particularly in the absence of indications of environmental hypothermia. PMID- 27356012 TI - Adipocere-The Fat of Graveyards. AB - Adipocere is an unusual product of fatty tissue decomposition that may occasionally be found in bodies. Two cases of diving fatalities in a limestone cave filled with fresh water are reported to demonstrate the features of adipocere, with a literature review. The bodies of a 20-year-old male and 22-year old female diver were retrieved 11 and 10 months after their deaths, respectively. Both bodies were putrefied with extensive adipocere formation characterized by the absence of epidermis with loss of cellular detail, with residual collagen fibers, and occasional hair follicles in the dermis. The most likely cause of death was accidental drowning possibly contributed to by equipment malfunction at depth. Adipocere formation is an unusual finding in bodies, particularly in Australia, that is facilitated by cold, wet, and anaerobic environments. If found at autopsy, it may give some indication of the environmental conditions that a body has been exposed to. PMID- 27356013 TI - Lethal Dengue Virus Infection. PMID- 27356014 TI - Sudden Death Due to Bilateral Pulmonary Thromboembolism Following Laparoscopic Cholecystectomy. AB - Cases of sudden death due to pulmonary thromboembolism (PTE) following laparoscopic surgery are very rare. The risk factors for PTE include sex, operation duration, age, obesity, and underlying diseases. The development of thromboprophylaxis according to specific risk factors has contributed to the decrease in postoperative mortality. Here, we describe the case of a 50-year-old patient with sudden death due to PTE at 24 hours after laparoscopic cholecystectomy. The origin of the thrombi were bilateral deep vein thromboses in both the lower extremities. No severe risk factors for PTE were detected in the patient, and pneumatic compression devices were used during the surgery for thromboprophylaxis. We believe that the accumulation of minor risk factors may have contributed to the onset of PTE. Hence, a more cautious assessment of the risk factors for PTE prior to surgery is required in such cases. PMID- 27356015 TI - An Autopsy Checklist: A Monitor of Safety and Risk Management. AB - Any autopsy has safety and risk management issues, which can arise in the preautopsy, autopsy, and postautopsy phases. The London Health Sciences Department of Pathology and Laboratory Medicine Autopsy Checklist was developed to address these issues. The current study assessed 1 measure of autopsy safety: the effectiveness of the checklist in documenting pathologists' communication of the actual or potential risk of blood-borne infections to support staff. Autopsy checklists for cases done in 2012 and 2013 were reviewed. The frequency of communication, as recorded in checklists, by pathologists to staff of previously diagnosed blood-borne infections (hepatitis B/C and human immunodeficiency virus) or the risk of infection based on lifestyle (eg, intravenous drug abuse) was tabulated. These data were compared with medical histories of the deceased and circumstances of their deaths described in the final autopsy reports. Information about blood-borne infections was recorded less frequently in the checklists compared with the final reports. Of 4 known human immunodeficiency virus cases, there was no checklist documentation in 3. All 11 hand injuries were documented. None of these cases had known infectious risks. The Autopsy Checklist is a standardized means of documenting safety and risk issues arising during the autopsy process, but its effectiveness relies on accurate completion. PMID- 27356016 TI - N-Doped TiO2 Nanobelts with Coexposed (001) and (101) Facets and Their Highly Efficient Visible-Light-Driven Photocatalytic Hydrogen Production. AB - To narrow the band gap (3.2 eV) of TiO2 and extend its practical applicability under sunlight, the doping with nonmetal elements has been used to tune TiO2 electronic structure. However, the doping also brings new recombination centers among the photoinduced charge carriers, which results in a quantum efficiency loss accordingly. It has been proved that the {101} facets of anatase TiO2 are beneficial to generating and transmitting more reductive electrons to promote the H2-evolution in the photoreduction reaction, and the {001} facets exhibit a higher photoreactivity to accelerate the reaction involved of photogenerated hole. Thus, it was considered by us that using the surface heterojunction composed of both {001} and {101} facets may depress the disadvantage of N doping. Fortunately, we successfully synthesized anatase N-doped TiO2 nanobelts with a surface heterojunction of coexposed (101) and (001) facets. As expected, it realized the charge pairs' spatial separation and showed higher photocatalytic activity under a visible-light ray: a hydrogen generation rate of 670 MUmol h(-1) g(-1) (much higher than others reported previously in literature of N-doped TiO2 nanobelts). PMID- 27356017 TI - Novel Technology for Locating Hidden Egyptian Tombs and Detailing Schlemm Canal Physiology. PMID- 27356018 TI - A site-selective hyaluronan-interferonalpha2a conjugate for the treatment of ovarian cancer. AB - While interferon alpha (IFNalpha) is used in several viral and cancer contexts, its efficacy against ovarian cancer (OC) is far from being incontrovertibly demonstrated and, more importantly, is hindered by heavy systemic side effects. To overcome these issues, here we propose a strategy that allows a targeted delivery of the cytokine, by conjugating IFNalpha2a with an aldehyde-modified form of hyaluronic acid (HA). The resulting HA-IFNalpha2a bioconjugate was biochemically and biologically characterized. The conjugation with HA did not substantially modified both the antiviral function and the anti-proliferative activity of the cytokine. Moreover, the induction of STAT1 phosphorylation and of a specific gene expression signature in different targets was retained. In vivo optical imaging biodistribution showed that the i.p.-injected HA-IFNalpha2a persisted into the peritoneal cavity longer than IFNalpha2a without being toxic for intraperitoneal organs, thus potentially enhancing the loco-regional therapeutic effect. Indeed, in OC xenograft mouse models bioconjugate significantly improved survival as compared to the free cytokine. Overall, HA IFNalpha2a bioconjugate disclosed an improved anticancer efficacy, and can be envisaged as a promising loco-regional treatment for OC. PMID- 27356019 TI - Systemic delivery of siRNA by aminated poly(alpha)glutamate for the treatment of solid tumors. AB - Small interfering RNA (siRNA) can silence the expression of a targeted gene in a process known as RNA interference (RNAi). As a consequence, RNAi has immense potential as a novel therapeutic approach in cancer targeted therapy. However, successful application of siRNA for therapeutic purposes is challenging due to its rapid renal clearance, degradation by RNases in the bloodstream, poor cellular penetration, immunogenicity and aggregation in the blood. In addition, the few oligonucleotide-based nanomedicines that reached clinical trials either go to the liver following systemic administration or are applied topically. Treatment of solid tumors requires selective distribution of siRNA to the target tissue, hence there is an unmet medical need for an efficacious and safe nano sized delivery system for their clinical use. To overcome these hurdles, we have designed, synthesized and physico-chemically characterized a novel nanocarrier based on aminated poly(alpha)glutamate (PGAamine). This cathepsin B-biodegradable polymer interacts electrostatically with the siRNA to form a nano-sized polyplex stable in plasma. Treatment with PGAamine-Rac1 siRNA polyplex (siRac1-polyplex) caused specific gene silencing by 80% in HeLa and SKOV-3 human ovarian adenocarcinoma cells as opposed to PGAamine-control non-targeting siRNA polyplex (siCtrl-polyplex) leading to inhibition of cell migration and wound healing abilities. A stepwise dose escalation was performed in order to determine the in vivo maximum tolerated dose (MTD). This was followed by intraperitoneal administration of siRac1-polyplex to mCherry-labeled ovarian adenocarcinoma bearing mice leading to preferred tumor accumulation of siRac1 (8-fold) which resulted in 38% Rac1 knockdown. Furthermore, the polyplex was administered intravenously to lung carcinoma-bearing mice in which it caused 33% Rac1 knockdown. These promising results led to efficacy studies administering systemic treatment with an anticancer siRNA, siPlk1-polyplex, which inhibited tumor growth by 73% and 87% compared with siCtrl-polyplex or saline-treated mice, respectively, leading to prolonged overall survival. These findings represent the first time that a polyaminated poly(alpha)glutamate polymer is used for an efficacious and safe tumor delivery of RNAi following systemic administration. PMID- 27356021 TI - Controlling uranyl oxo group interactions to group 14 elements using polypyrrolic Schiff-base macrocyclic ligands. AB - Heterodinuclear uranyl/group 14 complexes of the aryl- and anthracenyl-linked Schiff-base macrocyclic ligands LMe and LA were synthesised by reaction of UO2(H2L) with M{N(SiMe3)2}2 (M = Ge, Sn, Pb). For complexes of the anthracenyl linked ligand (LA) the group 14 metal sits out of the N4-donor plane by up to 0.7 A resulting in relatively short MOUO distances which decrease down the group; however, the solid state structures and IR spectroscopic analyses suggest little interaction occurs between the oxo and group 14 metal. In contrast, the smaller aryl-linked ligand (LMe) enforces greater interaction between the metals; only the PbII complex was cleanly accessible although this complex was relatively unstable in the presence of HN(SiMe3)2 and some organic oxidants. In this case, the equatorial coordination of pyridine-N-oxide causes a 0.08 A elongation of the endo UO bond and a clear interaction of the uranyl ion with the Pb(ii) cation in the second donor compartment. PMID- 27356020 TI - Relationships between measures of adiposity with subclinical atherosclerosis in patients with type 2 diabetes. AB - OBJECTIVE: Assess cross-sectional relationships between body mass index (BMI), waist circumference (WC), pericardial (PAT), visceral (VAT), and subcutaneous adipose tissue (SAT) volumes with calcified plaque (CP) in African Americans (AAs) and European Americans (EAs) with type 2 diabetes. METHODS: Computed tomography measured PAT, VAT, SAT, and CP in coronary arteries (CAC), carotid arteries, and aorta. Generalized estimating equations models were fitted to test for associations between adiposity and CP, stratified by ethnicity while accounting for familial correlations. RESULTS: AAs (N = 753) vs. EAs (N = 562) had significantly lower PAT and VAT, despite equal or higher BMI. In multivariable models adjusting for age, gender, education, HbA1c, statins, smoking, cardiovascular disease, hypertension, nephropathy, and C-reactive protein, PAT positively associated with presence of CAC in AAs (P < 0.001), not EAs (P = 0.68; ethnicity interaction P < 0.01). Inverse associations were detected between SAT and severity of aorta CP (P < 0.01) in AAs and between BMI, WC, and SAT with severity of aorta CP in all participants. CONCLUSIONS: Ethnic- and gender-specific differences in BMI, WC, PAT, SAT, and VAT were present in AAs and EAs with diabetes. Only PAT was positively associated with CAC in AAs; paradoxical inverse associations were seen between several other adiposity measures and subclinical cardiovascular disease. PMID- 27356022 TI - Isozyme Specific Allosteric Regulation of Human Sulfotransferase 1A1. AB - The human cytosolic sulfotransferases (SULTs) comprise a 13-member enzyme family that regulates the activities of hundreds, perhaps thousands, of signaling small molecules via regiospecific transfer of the sulfuryl moiety (-SO3) from PAPS (3' phosphoadenosine 5'-phosphosulfate) to the hydroxyls and amines of acceptors. Signaling molecules regulated by sulfonation include numerous steroid and thyroid hormones, epinephrine, serotonin, and dopamine. SULT1A1, a major phase II metabolism SULT isoform, is found at a high concentration in liver and has recently been show to harbor two allosteric binding sites, each of which binds a separate and complex class of compounds: the catechins (naturally occurring polyphenols) and nonsteroidal anti-inflammatory drugs. Among catechins, epigallocatechin gallate (EGCG) displays high affinity and specificity for SULT1A1. The allosteric network associated with either site has yet to be defined. Here, using equilibrium binding and pre-steady state studies, the network is shown to involve 14 distinct complexes. ECGG binds both the allosteric site and, relatively weakly, the active site of SULT1A1. It is not a SULT1A1 substrate but is sulfonated by SULT2A1. EGCG binds 17-fold more tightly when the active-site cap of the enzyme is closed by the binding of the nucleotide. When nucleotide is saturating, EGCG binds in two phases. In the first, it binds to the cap-open conformer; in the second, it traps the cap in the closed configuration. Cap closure encapsulates the nucleotide, preventing its release; hence, the EGCG induced cap stabilization slows nucleotide release, inhibiting turnover. Finally, a comprehensive quantitative model of the network is presented. PMID- 27356023 TI - Overview and diagnosis of multiple sclerosis. AB - Multiple sclerosis (MS), a chronic inflammatory disease of unknown etiology, involves an immunemediated attack of the central nervous system (CNS) that produces demyelination and axonal/neuronal damage, resulting in characteristic multifocal lesions apparent on magnetic resonance imaging and a variety of neurologic manifestations. The disease pathology is characterized by multifocal lesions within the CNS, in both the white matter and gray matter, with perivenular inflammatory cell infiltrates, demyelination, axonal transection, neuronal degeneration, and gliosis. MS pathogenesis is complex, as it involves both T- and B-cell mechanisms and is heterogeneous in presentation. Relatively recently, the historical 4 core clinical categories of MS were revised in an effort to improve characterization of the clinical course, better identify where a given patient is positioned in the disease spectrum, and to guide clinical studies. In young and middle-aged adults, MS is one of the most common contributors to neurologic disability, and it exerts detrimental effects on a patient's productivity and health-related quality of life. Typically, patients with MS have a long life span, although healthcare utilization increases over time. As a consequence, the disease places a substantial burden on patients and their caregivers/families, as well as employers, the healthcare system, and society. PMID- 27356024 TI - Economic burden of multiple sclerosis and the role of managed sare organizations in multiple sclerosis management. AB - Multiple sclerosis (MS) is disease that has an early age of onset and may intensify and subside with disease relapses or exacerbations interrupted by periods of stability. Because of this, patients, their families and caregivers, employers, and the entire healthcare system carry substantial clinical and economic burdens associated with the disease over of a period of many years. Although most patients with MS are covered by health insurance, the management landscape has become increasingly complex over the past decade with the introduction and approval of several new disease-modifying therapies that, while remarkably effective and well tolerated, usually come with a very high cost. Whereas the main goal of treating patients with MS is to prevent disease progression and disability, healthcare and benefit providers are faced with an ever-tipping balance point between effectively managing the disease and maximizing the value of high-cost disease-modifying therapies in an already overburdened healthcare system. Treatment of MS should be individualized, and shared decision making between patients and healthcare providers must be preserved. Healthcare providers and payers need to collaborate to ensure that resources are used optimally and not wasted, reducing both the clinical and economic burdens related to this complex chronic disorder. PMID- 27356025 TI - Current and emerging treatment of multiple sclerosis. AB - The treatment of multiple sclerosis (MS) falls into 3 categories: treatment of exacerbations, slowing disease progression with disease-modifying therapies (DMTs), and symptomatic therapies. The management of MS is becoming increasingly complex with the development of additional DMTs that, like the older DMTs, reduce the frequency and severity of relapses, and the accumulation of lesions detected by magnetic resonance imaging. Initiating treatment to slow or reverse inflammatory lesion formation early in the course of the disease is advocated as a way to prevent accumulation of disability. Nevertheless, there is a lack of comparative efficacy data and few clinical guidelines to aid healthcare providers in the optimal selection of DMTs. Given that some of the newer agents are associated with potentially serious, but rare, adverse events, careful consideration of the risk-benefit profile is necessary to minimize the risk to patients. This article provides an overview of the existing treatments for MS with an emphasis on DMTs and emerging therapies. PMID- 27356027 TI - Extracellular Release of Annexin A2 is Enhanced upon Oxidative Stress Response via the p38 MAPK Pathway after Low-Dose X-Ray Irradiation. AB - The extracellular microenvironment affects cellular responses to various stressors including radiation. Annexin A2, which was initially identified as an intracellular molecule, is also released into the extracellular environment and is known to regulate diverse cell surface events, however, the molecular mechanisms underlying its release are not well known. In this study, we found that in cultured human cancer and non-cancerous cells an extracellular release of annexin A2 was greatly enhanced 1-4 h after a single 20 cGy X-ray dose, but not after exposure to ultraviolet C (UVC) radiation. Extracellular release of annexin A2 was also enhanced after H2O2 and nicotine treatments, which was suppressed by pretreatment with the antioxidant, N-acetyl cysteine. Among the oxidative stress pathway molecules examined in HeLa cells, AMP-activated protein kinase alpha (AMPKalpha) and p38 mitogen-activated protein kinase (MAPK) were mostly activated by low-dose X-ray radiation, and the p38 MAPK inhibitor, SB203580, but not compound C (an AMPKalpha inhibitor), suppressed the enhancement of the annexin A2 extracellular release after low-dose X irradiation. In addition, the enhancement was suppressed in the cells in which p38alpha MAPK was downregulated by siRNA. HeLa cells and human cultured cells preirradiated with 20 cGy or precultured in media from low-dose X-irradiated cells showed an increase in resistance to radiation-induced cell death, and the increase was suppressed by treatment of the irradiated cell-derived media with anti-annexin A2 antibodies. In addition, extracellularly added recombinant annexin A2 conferred cellular radiation resistance. These results indicate that an oxidative stress-activated pathway via p38 MAPK was involved in the extracellular release of annexin A2, and this pathway was stimulated by low-dose X-ray irradiation. Furthermore, released annexin A2 may function in low-dose ionizing radiation-induced responses, such as radioresistance. PMID- 27356026 TI - Differences of psychological features in patients with heart failure with regard to gender and aetiology - Results of a CAPS-LOCK-HF (Complex Assessment of Psychological Status Located in Heart Failure) study. AB - OBJECTIVE: Objective of the study was to assess the psychological state of HF patients with reduced ejection fraction (HFrEF) with regard to gender and aetiology. METHODS: 758 patients with HFrEF (mean age - 64+/-11years, men - 79%, NYHA class III-IV - 40%, ischemic aetiology - 61%) in a prospective Polish multicenter Caps-Lock-HF study. Scores on five different self-report inventories: CISS, MHLC, GSES, BDI and modified Mini-MAC were compared between the sexes taking into account the aetiology of HFrEF. RESULTS: There were differences in the CISS and BDI score between the genders - women had higher CISS (emotion- and avoidance-oriented) and BDI (general score - 14.2+/-8.7 vs 12.3+/-8.6, P<0.05; subscale - somatic score - 7.3+/-3.7 vs 6.1+/-3.7, P<0.05). In the ischemic subpopulation, women had higher BDI (general and subscales) than men. In the non ischemic subpopulation the differences between genders were limited to CISS scale. In a multivariable analysis with demographic and clinical data female sex, NYHA class, atrial fibrillation and diabetes mellitus determined BDI score. Similarly, in the ischemic subpopulation, the female sex, NYHA class and atrial fibrillation determined the BDI, while in the non-ischemic population NYHA class was the only factor that influenced the BDI score. Adding the psychological data made a significant additional contribution to the prediction of depression status. CONCLUSIONS: There are distinct differences in psychological features with regard to gender in patients with HFrEF. Women demonstrate less favourable psychological characteristics. Gender-related differences in BDI score are especially explicit in patients with ischemic aetiology of HF. The BDI score is related to psychological predisposition. PMID- 27356028 TI - Biofilm Formation by Environmental Isolates of Salmonella and Their Sensitivity to Natural Antimicrobials. AB - The objective of this study was to determine reduction of Salmonella in biofilms by essential oils. Biofilm formation of 15 Salmonella isolates from conventional swine farm environment was evaluated by 96-well microtiter plate crystal violet and minimum biofilm eradication concentration (MBEC) assays. Only one of the 15 isolates was a strong biofilm producer as classified by crystal violet assay. All Salmonella isolates formed biofilm on MBEC assay. The curli expression was robust among strains S322 and S435 (Salmonella Infantis), S644, S777, S931, S953, and S977 (Salmonella Typhimurium) as observed by Congo red dye binding assay. The cell hydrophobicity varied with strains and growth phase of the strain; however, there was no significant difference in hydrophobicity of these strains. Natural antimicrobials were evaluated with MBEC assay for their bactericidal efficacy in reducing Salmonella in biofilms. Cinnamaldehyde and sporran at 1000 ppm significantly reduced Salmonella in biofilms. The bactericidal effect of these antimicrobials increased with their concentrations. Salmonella were reduced by 6 log CFU from their initial populations of 7-7.5 log CFU/cm(2) when 2000 ppm concentration of these antimicrobials were used. Salmonella were undetectable when 3000 ppm of cinnamaldehyde or sporran was used. Natural antimicrobials such as cinnamaldehyde and sporran can be used to reduce Salmonella in biofilms. PMID- 27356029 TI - Targeting of non-cycling cells of hypoxic tumors. PMID- 27356030 TI - Constructing Slow-Release Formulations of Metribuzin Based on Degradable Poly(3 hydroxybutyrate). AB - Experimental formulations of herbicide metribuzin embedded in matrices of degradable natural polymer poly(3-hydroxybutyrate) (P3HB) and its composites with poly(ethylene glycol) (PEG), poly-epsilon-caprolactone (PCL), and wood powder have been prepared in the form of pressed pellets containing 75% polymeric basis (pure P3HB or its composite with a second component at a ratio of 7:3) and 25% metribuzin. Incubation of formulations in soil laboratory systems led to the degradation of the matrix and herbicide release. The most active release of metribuzin (about 60% of the embedded herbicide over 35 days) was detected for the P3HB/PEG carrier compared to the P3HB, P3HB/wood, and P3HB/PCL forms (30 40%). Thus, the study shows that herbicide release can be controlled by the matrix formulation. Metribuzin formulations exerted a significant herbicidal effect on the plant Agrostis stolonifera, used as a weed plant model. Application of these long-term formulations will make it possible to reduce environmental release of chemicals, which will restrict the rate of their accumulation in trophic chains of ecosystems and abate their adverse effects on the biosphere. PMID- 27356031 TI - Participation in a Tele-Stroke Program Improves Timeliness of Intravenous Thrombolysis Delivery. AB - BACKGROUND: We sought to assess the effects of participation in a tele-stroke program on timeliness of intravenous tissue plasminogen activator (IVtPA) administration. METHODS: Among 259 consecutive acute ischemic stroke patients treated with IVtPA through the Rush tele-stroke program, we compared two cohorts: Period 1 (July 2011 to June 2013) and Period 2 (July 2013 to July 2014). We collected data on demographics, National Institutes of Health Stroke Scale (NIHSS), and times of last known normal (LKN), initiation of tele-stroke consult, and IVtPA administration. RESULTS: The mean age was 69.6 years, 56% were female, the mean NIHSS was 11.8, and 41.7% patients were transferred to the hub site. The mean time from initiation of tele-stroke consult to IVtPA administration was 42.2 min. Time from initiation of tele-stroke consult to IVtPA administration improved from Period 1 to Period 2 (49.9 min vs. 35 min, p < 0.0001). This improvement was due to faster mean time from initiation of tele-stroke consult to IVtPA advised (17.4 min vs. 12.5 min, p < 0.0001) and faster mean time from IVtPA advised to administration (33.1 min vs. 22.5 min, p < 0.0001). The mean time from LKN to IVtPA given was also significantly improved (148.6 min vs. 160.9 min, p 0.045). CONCLUSIONS: Participation in a tele-stroke program associated with improvement in the timeliness of IVtPA delivery. PMID- 27356032 TI - Development of an enzyme linked immunosorbent assay for the determination of phenothiazine drugs in meat and animal feeds. AB - In this study, 2-chlorophenothiazine was used to synthesize a hapten for production of monoclonal antibody. The obtained monoclonal antibody showed high crossreactivities to chlorpromazine, promethazine and perphenazine, and showed low crossreactivities to acepromazine and fluphenazine. After evaluation of three coating antigens, a heterologous competitive indirect enzyme linked immunosorbent assay was developed to determine the five phenothiazines in animal feeds and the residues of chlorpromazine, promethazine and perphenazine in meat. The crossreactivities to the five analytes were in a range of 2.4%-98%. The limits of detection for the five drugs in feeds were in a range of 0.1-3.0 MUg g-1, and that for chlorpromazine, promethazine and perphenazine in meat were in a range of 0.5-0.8 ng g-1. Their recoveries from standards fortified blank samples (chicken, pork and feeds) were in a range of 74.1%-96.5% with coefficients of variation of 6.4%-15.1%. Therefore, this method could be used as a rapid screen tool to determine phenothiazine drugs in animal feeds and animal derived foods. PMID- 27356034 TI - Self-Healing of Molecular Catalyst and Photosensitizer on Metal-Organic Framework: Robust Molecular System for Photocatalytic H2 Evolution from Water. AB - Inspired by self-repair mechanism of PSII in plants, we report a self-healing system which spontaneously repairs molecular catalyst and photosensitizer during photocatalytic H2 evolution. A bipyridine-embedded UiO-type metal-organic framework (MOF), namely Ptn_Ir_BUiO, which incorporated H2-evolving catalyst and photosensitizer, was synthesized and subject to photocatalytic H2 evolution reaction (HER). Impressively, HER with Pt0.1_Ir_BUiO showed very stable molecular photocatalysis without significant decrease in its activity and colloidal formation for 6.5 days at least; in the homogeneous counterpart, the molecular catalyst became a colloid just after 7.5 h. It was revealed that the arrangement of diimine sites which closely and densely surrounded the H2-evolving catalyst and photosensitizer in the MOF enabled such a highly efficient self-healing. PMID- 27356035 TI - Therapeutic approaches in clear cell and non-clear cell renal cell carcinoma. AB - Renal cell carcinoma (RCC) accounts for 2.4% of all malignancies worldwide diagnosed with 338,000 estimated new cases globally in 2012. In the last decade, the therapeutic landscape for RCC patients has changed tremendously. In this review, we will summarize the treatment options currently available for clear cell localized, advanced and metastatic RCC (mRCC); as stated in the ESMO clinical practice guidelines, the EAU guidelines and the NCCN guidelines. Furthermore, we will discuss the recommended therapies in patients diagnosed with non-clear cell tumours. PMID- 27356036 TI - Amyotrophic Lateral Sclerosis, 2016: existing therapies and the ongoing search for neuroprotection. AB - INTRODUCTION: Amyotrophic lateral sclerosis (ALS), one in a family of age-related neurodegenerative disorders, is marked by predominantly cryptogenic causes, partially elucidated pathophysiology, and elusive treatments. The challenges of ALS are illustrated by two decades of negative drug trials. AREAS COVERED: In this article, we lay out the current understanding of disease genesis and physiology in relation to drug development in ALS, stressing important accomplishments and gaps in knowledge. We briefly consider clinical ALS, the ongoing search for biomarkers, and the latest in trial design, highlighting major recent and ongoing clinical trials; and we discuss, in a concluding section on future directions, the prion-protein hypothesis of neurodegeneration and what steps can be taken to end the drought that has characterized drug discovery in ALS. EXPERT OPINION: Age-related neurodegenerative disorders are fast becoming major public health problems for the world's aging populations. Several agents offer promise in the near-term, but drug development is hampered by an interrelated cycle of obstacles surrounding etiological, physiological, and biomarkers discovery. It is time for the type of government-funded, public supported offensive on neurodegenerative disease that has been effective in other fields. PMID- 27356037 TI - Self-Assembly of Single-Layer CoAl-Layered Double Hydroxide Nanosheets on 3D Graphene Network Used as Highly Efficient Electrocatalyst for Oxygen Evolution Reaction. AB - A non-noble metal based 3D porous electrocatalyst is prepared by self-assembly of the liquid-exfoliated single-layer CoAl-layered double hydroxide nanosheets (CoAl NSs) onto 3D graphene network, which exhibits higher catalytic activity and better stability for electrochemical oxygen evolution reaction compared to the commercial IrO2 nanoparticle-based 3D porous electrocatalyst. PMID- 27356038 TI - Photo-induced Substitutive Introduction of the Aldoxime Functional Group to Carbon Chains: A Formal Formylation of Non-Acidic C(sp(3) )-H Bonds. AB - A photo-induced substitutive introduction of an aldoxime functional group to carbon chains was achieved using photo-excited 4-benzoylpyridine as a C(sp(3) )-H bond cleaving agent and arylsulfonyl oxime as an aldoxime precursor. The non acidic C-H bonds in various substances, including cycloalkanes, ethers, azacycles, and cyclic sulfides, were chemoselectively converted at ambient temperature under neutral conditions. The present transformation is a formal formylation of non-acidic C(sp(3) )-H bonds in a single step. PMID- 27356039 TI - Binding Analysis of Methyl-CpG Binding Domain of MeCP2 and Rett Syndrome Mutations. AB - Methyl-CpG binding protein 2 (MeCP2) binds to methylated cytosine in CpG island through its methyl-CpG binding domain (MBD). Here, the effects of the Rett syndrome-causing missense mutations on binding affinity of MBD to cytosine (C), methylcytosine (mC), hydroxymethylcytosine (hmC), formylcytosine (fC), and carboxylcytosine (caC) in CpG dinucleotide are investigated. MeCP2-MBD binds to mC-containing variants of double stranded CpG stronger than any other cytosine modified CpG with the strongest affinity to mC/mC. Thirteen MBD missense mutations show reduced binding affinity for mC/mC ranging with a 2-fold decrease for T158M to 88-fold for R111G. The binding affinities of these mutants to C/C are also reduced to various degrees except for T158M. Consistent with free energy perturbation analysis, correlation of binding affinity with protein unfolding allows for grouping mutations into three clusters. Correlation of the first cluster includes mutations that have a higher tendency to unfold and have lesser affinity to mC/mC and C/C. Mutations in the second cluster have similar structural stability but various affinities to mC/mC and C/C. R111G and A140V belong to the third cluster in which the loss of protein flexibility may underlie their reduction in binding affinity to mC/mC and C/C. Most notably, R111 emerges as the key structural element that modulates the specific contacts with mCpG. Implications of the results for the mCpG binding mechanism of MeCP2-MBD are discussed. These analyses provide new insights on the structure and function relationships in MeCP2-MBD and offer new clues to their roles in the pathology of Rett syndrome. PMID- 27356040 TI - Effect of further-neighbor interactions on the magnetization behaviors of the Ising model on a triangular lattice. AB - In this work, we study the magnetization behaviors of the classical Ising model on the triangular lattice using Monte Carlo simulations, and pay particular attention to the effect of further-neighbor interactions. Several fascinating spin states are identified to be stabilized in certain magnetic field regions, respectively, resulting in the magnetization plateaus at 2/3, 5/7, 7/9 and 5/6 of the saturation magnetization M S, in addition to the well-known plateaus at 0, 1/3 and 1/2 of M S. The stabilization of these interesting orders can be understood as the consequence of the competition between Zeeman energy and exchange energy. PMID- 27356042 TI - Norwegian male military veterans show low levels of mental health problems four years after deployment in Afghanistan. AB - BACKGROUND: Deployment of soldiers is associated with considerable rates of mental disorders after redeployment. AIMS: The aim of this study was to identity prevalence of probable mental disorders and associated factors among male Norwegian soldiers at a mean of 4 years following deployment to Afghanistan in 2001-2011. METHODS: The retrospective questionnaire-based study invited all Norwegian veterans deployed to Afghanistan from 2001-2011 to participate. The response rate was 59%, but only the 3403 men (47.5%) who completed all items of the four different screening instruments were used to define cases with mental health problems were included. Independent variables covered deployment and post deployment issues. RESULTS: The prevalence of subjects with mental health problems was 5.1% (95% CI = 4.4-5.9%) of the sample. Among deployment-related factors, physical and mental problems during deployment were most strongly associated with mental health problems after deployment. Among post-deployment factors high neuroticism and limitations in work, social, and family functions showed the strongest associations. In multivariable analysis, younger age at first deployment (OR = 0.95), neuroticism (OR = 6.40), increased current alcohol intake (OR = 3.08), impaired family function (OR = 1.91), more sleep problems (OR =1.13), and increased negative civilian life events (OR = 1.39) remained significantly associated with probable mental disorders. CONCLUSIONS: Among male Norwegian veterans from Afghanistan, the prevalence of mental health problems was low, and mainly associated with post-deployment factors. Veterans complaining of mental symptoms should be diagnosed, treated, and examined for other problems of life. PMID- 27356041 TI - Prevalence and characteristics of users of pre-exposure prophylaxis (PrEP) among men who have sex with men, San Francisco, 2014 in a cross-sectional survey: implications for disparities. AB - OBJECTIVES: Pre-exposure prophylaxis (PrEP) has gained a central role in prevention of HIV infection among men who have sex with men (MSM), particularly in San Francisco, California, USA. Programmes to enrol men in PrEP are being undertaken by a range of public and private organisations. PrEP will have the largest population impact if it reaches men who are most at risk for HIV infection, and is used in a manner that enables maximal efficacy. Access to PrEP also needs to be equitable. We report on the characteristics of men eligible for and using PrEP. METHODS: Data were from the 2014 implementation of National HIV Behavioural Surveillance (NHBS) among MSM in San Francisco. NHBS uses venue-based sampling as the national standard for sampling MSM. We compare proportions of demographic characteristics of MSM using versus not using PrEP who are HIV negative and meet Centers for Disease Control and Prevention guidelines to recommend PrEP. RESULTS: Overall, 64.1% of HIV-negative MSM in San Francisco would meet guidelines for PrEP use, while 9.2% of MSM overall and 14.5% of MSM eligible were using PrEP as of 2014. Men using PrEP are more likely to be white and of older age. There were no differences between men using and not using PrEP in terms of education, income and health insurance. CONCLUSIONS: PrEP roll-out efforts should attempt to increase reach for young, black and Hispanic MSM. Failure to equitably provide access to PrEP could exacerbate the US disparity in new HIV infections for men of colour. PMID- 27356043 TI - Dynamic Self-Assembly Adhesion of a Paraquat Droplet on a Pillar[5]arene Surface. AB - The adhesion of herbicide droplets on leaf surfaces plays an important role in the herbicide's adsorption by crops. How to control the adhesive binding which occurs through dynamic self-assembly between the macroscopic droplet and the surface is a challenging task. We introduce a host onto surfaces that controls the binding of guests in the paraquat droplets. The pillar[5]arene-functional surface showed the selective binding of paraquat droplets via the host-guest interaction. The work is promising for improving the efficiency of herbicides. PMID- 27356044 TI - Reactive oxygen species: sources, consequences and targeted therapy in type 2 diabetes. AB - Oxidative stress has been considered as a central mediator in the progression of diabetic complication. The intracellular reactive oxygen species (ROS) leads to oxidative stress and it is raised from the mitochondria as well as by activation of five major pathways: increased polyol pathway flux, activation of protein kinase C (PKC) pathway, increased formation of advanced glycation end products (AGEs), over activity of hexosamine pathway and increased production of angiotensin II. The increased ROS through these pathways leads to beta-cell dysfunction and insulin resistance, responsible for cell damage and death. This review not only highlights the sources of ROS production and their involvement in the progression of diabetes, but also emphasizes on pharmacological interventions and targeting of ROS in type 2 diabetes. This review summarizes the ROS as potential therapeutic targets, based on a putative mechanism in the progression of the diabetes. It also summarizes current knowledge of ROS activation in type 2 diabetes as well as ROS as a possible target for its treatment. Eventually, it would be a promising target for various strategies and drugs to modulate ROS levels in diabetes. PMID- 27356046 TI - In situ growth of ZIF-8 nanocrystals on layered double hydroxide nanosheets for enhanced CO2 capture. AB - A hexagonal nanosheet LDH@ZIF-8 composite was fabricated by in situ growth of ZIF 8 on Zn-Al LDH without adding any zinc precursor, and exhibited a CO2 adsorption capacity of 1.0 mmol g(-1) at room temperature and 1 bar, which was significantly higher than that of pure Zn-Al LDH or ZIF-8, indicating a synergy between ZIF-8 and Zn-Al LDH. PMID- 27356045 TI - Semisynthetic and in Vitro Phosphorylation of Alpha-Synuclein at Y39 Promotes Functional Partly Helical Membrane-Bound States Resembling Those Induced by PD Mutations. AB - Alpha-synuclein is a presynaptic protein of poorly understood function that is linked to both genetic and sporadic forms of Parkinson's disease. We have proposed that alpha-synuclein may function specifically at synaptic vesicles docked at the plasma membrane, and that the broken-helix state of the protein, comprising two antiparallel membrane-bound helices connected by a nonhelical linker, may target the protein to such docked vesicles by spanning between the vesicle and the plasma membrane. Here, we demonstrate that phosphorylation of alpha-synuclein at tyrosine 39, carried out by c-Abl in vivo, may facilitate interconversion of synuclein from the vesicle-bound extended-helix state to the broken-helix state. Specifically, in the presence of lipid vesicles, Y39 phosphorylation leads to decreased binding of a region corresponding to helix-2 of the broken-helix state, potentially freeing this region of the protein to interact with other membrane surfaces. This effect is largely recapitulated by the phosphomimetic mutation Y39E, and expression of this mutant in yeast results in decreased membrane localization. Intriguingly, the effects of Y39 phosphorylation on membrane binding closely resemble those of the recently reported disease linked mutation G51D. These findings suggest that Y39 phosphorylation could modulate functional aspects of alpha-synuclein and perhaps influence pathological aggregation of the protein as well. PMID- 27356047 TI - Living in your own home and being socially connected at 95 years and beyond: a qualitative study. AB - BACKGROUND: Being socially connected is linked to positively influencing older people's ability to remain living in their own homes and has shown to support independence and enhance well-being. AIM: To explore how individuals aged 95 years and older living in their own home remain socially connected. METHODS: Informed by a critical gerontological approach, semi-structured interviews with eight women and two men aged between 96 and 100 years were undertaken. Following transcription, data were thematically analysed. RESULTS: Three main themes illuminating social connectedness were identified: "Keeping company: staying connected with family and friends", "Doing things together: engaging with paid and unpaid helpers" and "Having pride and enjoyment: continuing with hobbies and interests". CONCLUSION: It is important that health professionals and social service providers recognise the importance of social connectedness, and provide a range of options to support continuing social connectedness and community engagement for older people. PMID- 27356048 TI - ConRad-Global Conference on Radiation Topics-Preparedness, Response, Protection and Research, Munich, 4-7 May 2015. PMID- 27356049 TI - Transcriptome Alterations In X-Irradiated Human Gingiva Fibroblasts. AB - Ionizing radiation is known to induce genomic lesions, such as DNA double strand breaks, whose repair can lead to mutations that can modulate cellular and organismal fate. Soon after radiation exposure, cells induce transcriptional changes and alterations of cell cycle programs to respond to the received DNA damage. Radiation-induced mutations occur through misrepair in a stochastic manner and increase the risk of developing cancers years after the incident, especially after high dose radiation exposures. Here, the authors analyzed the transcriptomic response of primary human gingival fibroblasts exposed to increasing doses of acute high dose-rate x rays. In the dataset obtained after 0.5 and 5 Gy x-ray exposures and two different repair intervals (0.5 h and 16 h), the authors discovered several radiation-induced fusion transcripts in conjunction with dose-dependent gene expression changes involving a total of 3,383 genes. Principal component analysis of repeated experiments revealed that the duration of the post-exposure repair intervals had a stronger impact than irradiation dose. Subsequent overrepresentation analyses showed a number of KEGG gene sets and WikiPathways, including pathways known to relate to radioresistance in fibroblasts (Wnt, integrin signaling). Moreover, a significant radiation induced modulation of microRNA targets was detected. The data sets on IR-induced transcriptomic alterations in primary gingival fibroblasts will facilitate genomic comparisons in various genotoxic exposure scenarios. PMID- 27356050 TI - Progenitor Cell Mobilization by Gamma-tocotrienol: A Promising Radiation Countermeasure. AB - This article reviews studies of progenitor mobilization with gamma-tocotrienol (GT3), a tocol under advanced development as a radiation countermeasure for acute radiation syndrome (ARS). GT3 protects mice against high doses of ionizing radiation and induces high levels of granulocyte colony-stimulating factor (G CSF). GT3-induced G-CSF in conjunction with AMD3100 (a chemokine receptor antagonist clinically used to improve the yield of mobilized progenitors) mobilizes progenitors; these mobilized progenitors mitigate injury when infused to mice exposed to acute, high-dose ionizing radiation. The administration of a G CSF antibody to GT3-injected donor mice abrogated the radiomitigative efficacy of blood or peripheral blood mononuclear cells (PBMC) in irradiated recipient mice. The efficacy of GT3-injected donor mice blood or PBMC was comparable to a recently published article involving blood or mononuclear cells obtained from mice injected with G-CSF. The injected progenitors were found to localize in various tissues of irradiated hosts. The authors demonstrate the efficacy of a bridging therapy in a preclinical animal model that allows the lymphohematopoietic system of severely immunocompromised mice to recover. This suggests that GT3 is a highly effective agent for radioprotection and mobilizing progenitors with significant therapeutic potential. Therefore, GT3 may be considered for further translational development and ultimately for use in humans. PMID- 27356051 TI - Forecasting the In Vivo Behavior of Radiocontaminants of Unknown Physicochemical Properties Using a Simple In Vitro Test. AB - An understanding of the "bioavailability" of disseminated radiocontaminants is a necessary adjunct in order to tailor treatment and to calculate dose. A simple test has been designed to predict the bioavailability of different actinide forms likely to be found after dissemination of radioactive elements by dispersal devices or nuclear reactor incidents. Plutonium (Pu) or Americium (Am) nitrate or MOX (U,PuO2) are immobilized in culture wells using a static gel phase simulating biological compartments (lung, wound, etc.). Gels are incubated in a fluid phase representing physiological media (plasma, sweat, etc.). Transfer of radionuclide from static to fluid phase reflects contaminant bioavailability. After 48 h of incubation in physiological saline, Am transfer from static to fluid phase was greater than for Pu (70% vs. 15% of initial activity). Transfer of Pu or Am was markedly less from the oxide form of the two elements (1% Am and 0.05% Pu transferred). Medium representing intracellular lysosomal fluid (pH 4) increased transfer of Pu and Am, whereas culture medium including serum reduced actinide transfer. Actinide transfer was also reduced by elements of the extracellular matrix present in the static gel phase. Increasing DTPA concentrations (5 to 500 MUM) to the fluid phase significantly enhanced transfer of Pu and Am. Although this agarose gel cannot fully represent in vivo complexity, this simple test can be used to investigate and predict the behavior in vivo of radiocontaminants to support medical treatments and medical forensic investigations. PMID- 27356052 TI - Metrology for Radiological Early Warning Networks in Europe ("METROERM")-A Joint European Metrology Research Project. AB - As a consequence of the Chernobyl nuclear power plant accident in 1986, all European countries have installed automatic dosimetry network stations as well as air sampling systems for the monitoring of airborne radioactivity. In Europe, at present, almost 5,000 stations measure dose rate values in nearly real time. In addition, a few hundred air samplers are operated. Most of them need extended accumulation times with no real-time capability. National dose rate data are provided to the European Commission (EC) via the EUropean Radiological Data Exchange Platform (EURDEP). In case of a nuclear emergency with transboundary implications, the EC may issue momentous recommendations to EU member states based on the radiological data collected by EURDEP. These recommendations may affect millions of people and could have severe economic and sociological consequences. Therefore, the reliability of the EURDEP data is of key importance. Unfortunately, the dose rate and activity concentration data are not harmonized between the different networks. Therefore, within the framework of the European Metrology Research Programme (EMRP), 16 European institutions formed the consortium MetroERM with the aim to improve the metrological foundation of measurements and to introduce a pan-European harmonization for the collation and evaluation of radiological data in early warning network systems. In addition, a new generation of detector systems based on spectrometers capable of providing both reliable dose rate values as well as nuclide specific information in real time are in development. The MetroERM project and its first results will be presented and discussed in this article. PMID- 27356053 TI - Occupational Doses from the use of Thoriated Optical Components. AB - As a compound of high refractive optical glasses, thorium still is present in some professionally used systems-especially in optical equipment with military use. The possible exposure concerns the head and especially the eye lens, whose radiation sensitivity has been reevaluated. The dose rate measurements of the contribution of beta- and gamma-emission by the nuclei of the decay chain of Th are presented for isolated lenses and for the entire optical system, and the dose quantities H'(0.07) and H*(10) are identified. Exposure scenarios for optical technicians and users are evaluated separately. The levels of dose rates for the inspected optical systems are below those requiring radiation protection measures even for extended working time or unintentional use. PMID- 27356054 TI - Case Report: Industrial X-Ray Injury Treated With Non-Cultured Autologous Adipose Derived Stromal Vascular Fraction (SVF). AB - Local cutaneous injuries induced by ionizing radiation (IR) are difficult to treat. Many have reported local injection of adipose-derived stromal vascular fraction (SVF), often with additional therapies, as an effective treatment of IR induced injury even after other local therapies have failed. The authors report a case of a locally recurrent, IR-induced wound that was treated with autologous, non-cultured SVF without other concurrent therapy. A nondestructive testing technician was exposed to 130 kVp x rays to his non-dominant right thumb on 5 October 2011. The wound healed 4 mo after initial conservative therapy with oral/topical alpha-tocopherol, oral pentoxifylline, naproxen sodium, low-dose oral steroids, topical steroids, hyperbaric oxygen therapy (HBOT), oral antihistamines, and topical aloe vera. Remission lasted approximately 17 mo with one minor relapse in July 2012 after minimal trauma and subsequent healing. Aggressive wound breakdown during June 2013 required additional therapy with HBOT. An erythematous, annular papule developed over the following 12 mo (during which time the patient was not undergoing prescribed treatment). Electron paramagnetic resonance (EPR) done more than 2 mo after exposure to IR revealed dose estimates of 14 +/- 3 Gy and 19 +/- 6 Gy from two centers using different EPR techniques. The patient underwent debridement of the 0.5 cm papular area, followed by SVF injection into and around the wound bed and throughout the thumb without complication. Eleven months post SVF injection, the patient has been essentially asymptomatic with an intact integument. These results raise the possibility of prolonged benefit from SVF therapy without the use of cytokines. Since there is currently no consensus on the use of isolated SVF therapy in chronic, local IR-induced injury, assessment of this approach in an appropriately powered, controlled trial in experimental animals with local radiation injury appears to be indicated. PMID- 27356055 TI - Contribution of INTRAMUSCULAR Autologous Adipose Tissue-Derived Stem Cell Injections to Treat Cutaneous Radiation Syndrome: Preliminary Results. AB - Cutaneous radiation syndrome caused by high dose located irradiation is characterized by delayed symptoms, incomplete wound healing, and poor revascularization. Subcutaneous adipose tissue derived stromal/stem cells have been shown to improve skin repair in a minipig model of cutaneous radiation syndrome despite a subcutaneous defect being a consequence of radio-induced muscular fibrosis. Based on the pro-myogenic potential of stromal/stem cells, a new protocol combining subcutaneous and intramuscular injections was evaluated in a preliminary study. Six female minipigs were locally irradiated at the dose of 50 Gy using a Co source (0.6 Gy min) and randomly divided into two groups. Three animals received the vehicle (phosphate-buffer-saline solution) and three animals received three injections of 75 * 10 adipose tissue derived stromal/stem cells each time (day 25, 46, and 66 post-irradiation). Pigs were euthanized on day 76 post-irradiation before development of clinical skin symptoms. All minipigs exhibited a homogeneous skin evolution. Macroscopic observation of irradiated muscles showed prominent fibrosis and necrosis areas in controls as opposed to adipose tissue-derived stromal/stem cells injected animals. Moreover, muscle biopsy analysis highlighted a recruitment of myofibroblasts (Immune Reactive Score: p < 0.01), an interleukin 10 secretion and a muscle regeneration pathway activation after intramuscular injections of adipose tissue-derived stromal/stem cells (western-blot: respectively, 200-fold change difference and twofold higher in treated animals). Globally, these preliminary data suggest that intramuscular injections of adipose tissue-derived stromal/stem cells improve muscle regeneration in the cutaneous-radiation syndrome. Further work is ongoing to evaluate this therapeutic strategy on a larger animal number with a longer clinical follow-up. PMID- 27356056 TI - Kevlar(r) as a Potential Accident Radiation Dosimeter for First Responders, Law Enforcement and Military Personnel. AB - Today the armed forces and law enforcement personnel wear body armor, helmets, and flak jackets composed substantially of Kevlar(r) fiber to prevent bodily injury or death resulting from physical, ballistic, stab, and slash attacks. Therefore, there is a high probability that during a radiation accident or its aftermath, the Kevlar(r)-composed body armor will be irradiated. Preliminary study with samples of Kevlar(r) foundation fabric obtained from body armor used by the U.S. Marine Corps has shown that all samples evaluated demonstrated an EPR signal, and this signal increased with radiation dose. Based on these results, the authors predict that, with individual calibration, exposure at dose above 1 Gy can be reliably detected in Kevlar(r) samples obtained from body armor. As a result of these measurements, a post-event reconstruction of exposure dose can be obtained by taking various samples throughout the armor body and helmet worn by the same irradiated individual. The doses can be used to create a whole-body dose map that would be of vital importance in a case of a partial body or heterogeneous exposure. PMID- 27356057 TI - Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model. AB - Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (gamma-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1 14 Gy, Co gamma-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome. PMID- 27356058 TI - Radiation Injury Treatment Network(r): Preparedness Through a Coalition of Cancer Centers. AB - This article provides an overview of Radiation Injury Treatment Network(r) (RITN), its preparedness activities and capabilities, including training and educating over 11,500 hospital staff, coordinating over 500 exercises, developing treatment guidelines, developing standard operating procedures, and being recognized by the U.S. federal government as a national response asset. The RITN provides comprehensive evaluation and treatment for victims with marrow toxic injuries. Many of the casualties from the detonation of an improvised nuclear device (IND) (a.k.a. terrorist nuclear bomb) with only radiation injuries will be salvageable; however, they would require outpatient and/or inpatient care. Recognizing this, the U.S. National Marrow Donor Program (NMDP), U.S. Navy, and American Society for Blood and Marrow Transplantation (ASBMT) collaboratively developed RITN, which comprises medical centers with expertise in the management of bone marrow failure. The medical community will undoubtedly be taxed by the resulting medical surge from an IND despite the well-defined United States emergency medical system, the National Disaster Medical System; however, one area that is unique for radiological disasters is the care for casualties with acute radiation syndrome. Hematologists and oncologists purposefully expose their cancer patients to high doses of radiation and toxic chemicals for chemotherapy as they treat their patients, resulting in symptoms not unlike casualties with exposure to ionizing radiation from a radiological disaster. This makes the staff from cancer centers ideal for the specialized care that will be required for thousands of casualties following a mass casualty radiological incident. The RITN is a model for how a collaborative effort can fill a readiness gap-through its network of 76 hospitals, blood donor centers, and cord blood banks, the RITN is preparing to provide outpatient care and specialized supportive care to up to 63,000 radiological casualties. PMID- 27356059 TI - Investigation of Abscopal and Bystander Effects in Immunocompromised Mice After Exposure to Pencilbeam and Microbeam Synchrotron Radiation. AB - Out-of-field effects are of considerable interest in radiotherapy. The mechanisms are poorly understood but are thought to involve signaling processes, which induce responses in non-targeted cells and tissues. The immune response is thought to play a role. The goal of this research was to study the induction of abscopal effects in the bladders of NU-Foxn1 mice after irradiating their brains using Pencil Beam (PB) or microbeam (MRT) irradiation at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. Athymic nude mice injected with F98 glioma cells into their right cerebral hemisphere 7 d earlier were treated with either MRT or PB. After recovery times of 2, 12, and 48 h, the urinary bladders were extracted and cultured as tissue explants for 24 h. The growth medium containing the potential signaling factors was harvested, filtered, and transferred to HaCaT reporter cells to assess their clonogenic survival and calcium signaling potential. The results show that in the tumor-free mice, both treatment modalities produce strong bystander/abscopal signals using the clonogenic reporter assay; however, the calcium data do not support a calcium channel mediated mechanism. The presence of a tumor reduces or reverses the effect. PB produced significantly stronger effects in the bladders of tumor bearing animals. The authors conclude that immunocompromised mice produce signals, which can alter the response of unirradiated reporter cells; however, a novel mechanism appears to be involved. PMID- 27356060 TI - Significance of Bioindicators for Early Predictions on Diagnosis and Therapy of Irradiated Minipigs. AB - Decisions on whether to start a therapeutic intervention for management of the Acute Radiation Syndrome (ARS) should be made early after exposure, and it should be based on readily available clinical signs and laboratory parameters. Here, the authors use the minipig to assess if early prediction of the later developing clinical outcome and necessity of therapeutic interventions can be determined within the first 3 d after exposure and whether it is comparable to human data. Retrospective analysis of data accumulated in the period 2009-2012 was used. Male Gottingen minipigs (age 4-5 mo, weight 9-10 kg) were irradiated (or sham irradiated) bilaterally with gamma-photons (Co, 0.5-0.6 Gy min) in the dose range of 1.6-12 Gy. Complete blood counts, serum chemistry, and clinical symptoms were collected up to 60 d after irradiation in untreated minipigs. Changes in these early parameters (up to 3 d after exposure) were correlated with later occurrence (10-60 d after irradiation) of (1) hematological severity scores, (2) severe thrombocytopenia, (3) severe neutropenia, as well as need for (4) therapeutic intervention, (5) administration of cytokines/antibiotics, or (6) thrombocyte transfusions. Binary endpoints were analyzed using logistic regression analysis and calculating receiver operating characteristic (ROC) curves. Most predictive were decreased lymphocyte counts and increases in body temperature at 3 h after irradiation. These data corroborate earlier findings performed on human radiation victims suffering from severe hematological syndrome and provide further evidence for the suitability of the minipig model as a potential alternative non-rodent animal model. PMID- 27356062 TI - Combining Radiation Epidemiology With Molecular Biology-Changing From Health Risk Estimates to Therapeutic Intervention. AB - The authors herein summarize six presentations dedicated to the key session "molecular radiation epidemiology" of the ConRad meeting 2015. These presentations were chosen in order to highlight the promise when combining conventional radiation epidemiology with molecular biology. Conventional radiation epidemiology uses dose estimates for risk predictions on health. However, combined with molecular biology, dose-dependent bioindicators of effect hold the promise to improve clinical diagnostics and to provide target molecules for potential therapeutic intervention. One out of the six presentations exemplified the use of radiation-induced molecular changes as biomarkers of exposure by measuring stabile chromosomal translocations. The remaining five presentations focused on molecular changes used as bioindicators of the effect. These bioindicators of the effect could be used for diagnostic purposes on colon cancers (genomic instability), thyroid cancer (CLIP2), or head and neck squamous cell cancers. Therapeutic implications of gene expression changes were examined in Chernobyl thyroid cancer victims and Mayak workers. PMID- 27356061 TI - Evaluating the Special Needs of The Military for Radiation Biodosimetry for Tactical Warfare Against Deployed Troops: Comparing Military to Civilian Needs for Biodosimetry Methods. AB - The aim of this paper is to delineate characteristics of biodosimetry most suitable for assessing individuals who have potentially been exposed to significant radiation from a nuclear device explosion when the primary population targeted by the explosion and needing rapid assessment for triage is civilians vs. deployed military personnel. The authors first carry out a systematic analysis of the requirements for biodosimetry to meet the military's needs to assess deployed troops in a warfare situation, which include accomplishing the military mission. Then the military's special capabilities to respond and carry out biodosimetry for deployed troops in warfare are compared and contrasted systematically, in contrast to those available to respond and conduct biodosimetry for civilians who have been targeted by terrorists, for example. Then the effectiveness of different biodosimetry methods to address military vs. civilian needs and capabilities in these scenarios was compared and, using five representative types of biodosimetry with sufficient published data to be useful for the simulations, the number of individuals are estimated who could be assessed by military vs. civilian responders within the timeframe needed for triage decisions. Analyses based on these scenarios indicate that, in comparison to responses for a civilian population, a wartime military response for deployed troops has both more complex requirements for and greater capabilities to use different types of biodosimetry to evaluate radiation exposure in a very short timeframe after the exposure occurs. Greater complexity for the deployed military is based on factors such as a greater likelihood of partial or whole body exposure, conditions that include exposure to neutrons, and a greater likelihood of combined injury. These simulations showed, for both the military and civilian response, that a very fast rate of initiating the processing (24,000 d) is needed to have at least some methods capable of completing the assessment of 50,000 people within a 2- or 6-d timeframe following exposure. This in turn suggests a very high capacity (i.e., laboratories, devices, supplies and expertise) would be necessary to achieve these rates. These simulations also demonstrated the practical importance of the military's superior capacity to minimize time to transport samples to offsite facilities and use the results to carry out triage quickly. Assuming sufficient resources and the fastest daily rate to initiate processing victims, the military scenario revealed that two biodosimetry methods could achieve the necessary throughput to triage 50,000 victims in 2 d (i.e., the timeframe needed for injured victims), and all five achieved the targeted throughput within 6 d. In contrast, simulations based on the civilian scenario revealed that no method could process 50,000 people in 2 d and only two could succeed within 6 d. PMID- 27356063 TI - Chronic Lymphocytic Leukemia in Chornobyl Cleanup Workers. AB - This paper describes the chronic lymphocytic leukemia (CLL) incidence in a cohort of 110,645 (enlarged later to 152,520) male Ukrainian cleanup workers of the Chornobyl (Chernobyl) accident who were exposed to a range of radiation doses over the 1986-1990 time period. The standardized incidence rates are presented for a 27-y period after the exposure. For 2007-2012 period, the authors have identified the incident CLL cases in an enlarged cohort of 152,520 persons by linkage of the cohort file with the Ukrainian National Cancer Registry (NCRU). CLL data for the previous period (1987-2006) were identified in a frame of the Ukrainian-American leukemia study in the original cohort of 110,645 male clean-up workers. A significant CLL incidence excess was shown for the entire study period 1987-2012, with more prominent levels for the earliest years (1987-1996) when the standardized incidence rate (SIR) value was estimated to be 3.61 with 95% confidence interval from 2.32 to 4.91. In 2007-2012, the CLL incidence decreased substantially but still exceeded the national level although not significantly. In parallel, the several studies were performed at the National Research Center for Radiation Medicine (NRCRM) to explore if any clinical and cytogenetic features of CLL existed in the clean-up workers. The clinical study included 80 exposed and 70 unexposed CLL cases. Among the major clinical differences of the CLL course in the clean-up workers were a shorter period of white blood cells (WBC) doubling (10.7 vs. 18.0; p<0.001), frequent infectious episodes, lymphoadenopathy and hepatosplenomegaly (37 vs. 16), higher expression for CD38, and lower expression for ZAP-70 antigen. PMID- 27356064 TI - Radiation-epidemiological Study of Cerebrovascular Diseases in the Cohort of Russian Recovery Operation Workers of the Chernobyl Accident. AB - The paper presents an analysis of the incidence of cerebrovascular diseases (CeVD) in the cohort of Russian workers involved in recovery tasks after the Chernobyl accident. The studied cohort consists of 53,772 recovery operation workers (liquidators) who arrived in the zone of the Chernobyl accident within the first year after this accident (26 April 1986-26 April 1987). The mean external whole body dose in the cohort was 0.161 Gy, while individual doses varied from 0.0001 Gy to 1.42 Gy. During the follow-up period 1986-2012, a total of 23,264 cases of CeVD were diagnosed as a result of annual health examinations. A Poisson regression model was applied for estimation of radiation risks and for an assessment of other risk factors of CeVD. The following factors were considered as risk factors for CeVD: the dose, duration of the liquidators' work in the Chernobyl zone, and the concomitant diseases (hypertension, ischemic heart disease, atherosclerosis, and diabetes). The baseline incidence of CeVD is statistically significantly (p < 0.001) associated with all studied concomitant diseases. The incidence of CeVD has revealed a statistically significant dose response with the lack of a latent period and with the average ERR/Gy = 0.45, 95% CI: (0.28, 0.62), p < 0.001. Radiation risks of CeVD statistically significantly (p = 0.03) varied with the duration of liquidators' stay in the Chernobyl zone; for those who stayed in the Chernobyl zone less than 6 wk, ERR/Gy = 0.64, 95% CI = (0.38; 0.93), p < 0.001. Among studied concomitant diseases, diabetes mellitus statistically significantly (p = 0.002) increases the radiation risk of CeVD: for liquidators with diagnosed diabetes, ERR/Gy = 1.29. PMID- 27356065 TI - Adult Mesenchymal Stem Cells and Radiation Injury. AB - Recent understanding of the cellular and molecular signaling activations in adult mesenchymal stem cells (MSCs) has provided new insights into their potential clinical applications, particularly for tissue repair and regeneration. This review focuses on these advances, specifically in the context of self-renewal for tissue repair and recovery after radiation injury. Thus far, MSCs have been characterized extensively and shown to be useful in mitigation and therapy for acute radiation syndrome and cognitive dysfunction. Use of MSCs for treating radiation injury alone or in combination with additional trauma is foreseeable. PMID- 27356066 TI - Reconsidering Current Decorporation Strategies after Incorporation of Radionuclides. AB - In the case of a nuclear accident or a terrorist attack by a "dirty bomb," there is a risk of external and internal contamination with radionuclides in addition to external irradiation. Internal irradiation as a consequence of radionuclide incorporation is associated with a higher risk of stochastic radiation effects (e.g., tumors). Decorporation treatment will enhance the elimination of radionuclides and reduce the committed effective dose as a metric of stochastic health effects. Although treatment efficacy is better when started early, beginning the therapy without knowing the committed effective dose may unnecessarily expose the patient to the side effects of the medication. The question is: Delay the therapy to wait for the results of internal dosimetry or start the therapy promptly on spec? To prove insight into this question, a selective review of the literature was conducted. The importance of the initiation time of treatment in the efficacy of decorporation treatment can be explained with pharmacokinetic laws and first order processes determining the disposition of xenobiotics in the organism. Nevertheless, there is no internationally accepted standard on when to start a decorporation therapy (exception: iodide). The "precautionary approach," emphasizing the importance of the committed effective dose for the indication of treatment, is competing with the "urgent approach" advocating the administration of medication "a priori" within several hours. A review of the literature actually indicates that the most important drugs used for decorporation are well tolerated with few adverse effects. In consideration of the higher efficacy and the low side-effects of a short-term treatment, initiating decorporation therapy as soon as possible after internal contamination, even before the committed effective dose has been assessed, appears to be a reasonable approach. The decision of continuation or discontinuation of the therapy should be taken after internal dosimetry is completed on the basis of the committed effective dose. PMID- 27356068 TI - Evaluation of the Response to the Fukushima Accident. AB - The cause for the severity of the Fukushima nuclear accident is explained, and the radiological consequences are assessed. Moreover, the non-radiological effects are critically evaluated and failures in onsite and offsite emergency response highlighted. In conclusion, disregarding the principle of justification, the evacuation of residents and hospital patients was implemented too rigorously, resulting in unnecessary fatalities due to the protective action. PMID- 27356067 TI - The Role of Proinflammatory Cytokine Interleukin-18 in Radiation Injury. AB - Massive radiation-induced inflammatory factors released from injured cells may cause innate and acquired immune reactions that can further result in stress response signal activity-induced local and systemic damage. IL-1 family members IL-1beta, IL-18, and IL-33 play key roles in inflammatory and immune responses and have been recognized to have significant influences on the pathogenesis of diseases. IL-1beta, IL-18, and IL-33 share similarities of cytokine biology, but differences exist in signaling pathways. A key component of the inflammatory reaction is the inflammasome, which is a caspase-1-containing multiprotein oligomer. Pathological stimuli such as radiation can induce inflammasome and caspase-1 activation, and subsequently cause maturation (activation) of pro-forms of IL-1 and IL-18 upon caspase-1 cleavage. This caspase-1 dependent and IL-1 and IL-18 associated cell damage is defined as pyroptosis. Activated IL-1 and IL-18 as proinflammatory cytokines drive pathology at different immune and inflammatory disorders through Toll-like receptor (TLR) signaling. While the mechanisms of IL 1beta-induced pathophysiology of diseases have been well studied, IL-18 has received less attention. The author recently reported that gamma radiation highly increased IL-1beta, IL-18 and IL-33 expression in mouse thymus, spleen and/or bone marrow cells; also circulating IL-18 can be used as a radiation biomarker to track radiation injury in mice, minipigs, and nonhuman primates. This mini-review focuses on the role of IL-18 in response to gamma radiation-induced injury. PMID- 27356069 TI - Missions of the French Defense Radiation Protection Service Concerning The Medical Management of Radio-contaminated Patients. AB - The French Defense Radiation Protection Service (SPRA) is an institution of the French Armed Forces (SSA) that provides technical support in radiation protection matters for French military units. It provides services for the armed forces and when necessary for the national public health system. The aim of this note is to describe the variety of services provided by the SPRA in France and abroad, not only in a military context but also in the broader field of radiation protection. PMID- 27356070 TI - The New "Normal": Stakeholders and Radiation Protection Limits in a Post-9/11 World. AB - With the recent upsurge in worldwide terrorism, the prospects for a radiation terrorism event have greatly increased. Current recommendations regarding recovery from such an event specify that decisions about the extent of radiological cleanup will be dependent upon stakeholder acceptance of the risk levels. The case is made here that stakeholders are currently not prepared to make decisions collectively about the acceptability of risk levels and will be even less capable during the aftermath of an attack when a consensus among stakeholders is unlikely to be achieved. In order to better prepare stakeholders to make risk decisions after an attack, there needs to be at least some limited radiation training for people in locations that are likely terrorist targets, and this training is best delivered before a radiological incident has occurred. Additionally, the training should focus on individualized risk assessment based on personal radiation doses and should emphasize that individuals have the ability to control their personal dose by limiting the time that they spend in "zones" that have relatively high contamination levels and restricting their intake of specific contaminated foods. By raising stakeholder consciousness before an incident occurs and reducing decisions about the acceptability of risk to the level of the individual rather than the entire group, individual stakeholders will be empowered to become more fully engaged in the recovery process, more in control of their own lives, and less dependent upon radiation protection professionals to make global decisions about the acceptability of radiation risks on their behalf. PMID- 27356074 TI - Fertility and Early Pregnancy Outcomes Following Conservative Treatment for Cervical Intraepithelial Neoplasia and Early Cervical Cancer. AB - Clinical Question: Does local conservative treatment for cervical intraepithelial neoplasia and early invasive cervical cancer adversely affect successful conception and early pregnancy outcomes in the first and second trimester (<24 weeks of gestation)? Clinical Application: Local cervical treatment does not adversely affect fertility or first trimester miscarriage, although it is associated with a significant increase in the risk of second trimester miscarriages. PMID- 27356075 TI - Associations Between TGFA/TGFB3/MSX1 Gene Polymorphisms and Congenital Non Syndromic Hearing Impairment in a Chinese Population. AB - BACKGROUND The aim of this study was to investigate whether the TGFA/TGFB3/MSX1 gene polymorphisms and haplotypes lead to individual differences between congenital non-syndromic hearing impairment (NSHI) patients and normal people in a Chinese population and to analyze the risk factors for NSHI. MATERIAL AND METHODS Between December 2010 and September 2014, 343 congenital NSHI patients were recruited as cases, and 272 healthy subjects were recruited as controls. Denaturing high-performance liquid chromatography (DHPLC) was used to identify genotypes, SHEsis software was used to conduct gene linkage disequilibrium and haplotype analyses, and regression analysis was performed to identify risk factors for congenital NSHI. RESULTS The distribution of genotype frequencies and allele frequencies of TGFA rs3771494, TGFB3 rs3917201 and rs2268626, and MSX1 rs3821949 and rs62636562 were significantly different between the case and the control groups (all P<0.05). TGFA/TGFB3/MSX1 gene rs3771494, rs1058213, rs3917201, rs2268626, rs3821949, and rs62636562 haplotype analysis showed that haplotype CCGTAC and TTACGT might be protective factors (both P<0.001), while TTGCGC might be a risk factor for the normal population (P<0.001). The other risk factors include paternal smoking, advanced maternal age, maternal sickness history, maternal contact with pesticides or similar drugs, maternal abortion history, maternal medication history, maternal passive smoking history during pregnancy, rs3771494 CT, rs2268626 CC and TC, and rs3821949 GG and AG genotypes were risk factors (all P<0.05), while maternal vitamin supplements during pregnancy, rs3917201 GA, rs62636562 TT and CT genotypes were protective factors for congenital NSHI (all P<0.05). CONCLUSIONS rs3771494, rs3917201, rs2268626, rs3821949 and rs62636562 might be associated with congenital NSHI. PMID- 27356076 TI - Endoscopic clip closure of a duodenocolic fistula secondary to a migrated biliary stent. PMID- 27356077 TI - Small Cation-Based High-Performance Energetic Nitraminofurazanates. AB - Large nitramino-substituted furazan anions were combined with small cations (hydroxylammonium, hydrazinium, and ammonium) to form a series of energetic salts that was fully characterized. The structures of several of the compounds (1 a, 2 a, 3 a, and 4 a) were further confirmed by single-crystal X-ray diffraction. Based on their physiochemical properties, such as density, thermal stability, and sensitivity, together with the calculated detonation properties, it was found that they exhibit good detonation performance and have potential application as high-energy-density materials. PMID- 27356078 TI - An Alkaline-Stable, Metal Hydroxide Mimicking Metal-Organic Framework for Efficient Electrocatalytic Oxygen Evolution. AB - Postsynthetic ion exchange of [Co2(MU-Cl)2(btta)] (MAF-X27-Cl, H2bbta =1H,5H benzo(1,2-d:4,5-d')bistriazole) possessing open metal sites on its pore surface yields a material [Co2(MU-OH)2(bbta)] (MAF-X27-OH) functionalized by both open metal sites and hydroxide ligands, giving drastically improved electrocatalytic activities for the oxygen evolution reaction (an overpotential of 292 mV at 10.0 mA cm(-2) in 1.0 M KOH solution). Isotope tracing experiments further confirm that the hydroxide ligands are involved in the OER process to provide a low energy intraframework coupling pathway. PMID- 27356079 TI - Reconciling movement and exercise with pain neuroscience education: A case for consistent education. AB - This article will introduce a conceptual framework of kinesthetic education that is consistent with and reinforces pain neuroscience education. This article will also provide some specific guidance for integrating pain neuroscience education with exercise and movement in a more congruent manner. Our belief is that this will enhance the effectiveness of specific movement approaches such as graded exposure techniques. Over the past decade, a new paradigm of pain education has been explored in an effort to improve patient outcomes. Using advances in pain neuroscience, patients are educated in the biological and physiological processes involved in their pain experience. Growing evidence supports the ability of pain neuroscience education (PNE) to positively impact a person's pain ratings, disability, pain catastrophization, and movement limitations. What is often overlooked, however, is the consistency between the messages of PNE and those of other therapeutic interventions, including movement therapies. This article proposes the following: education provided in isolation will be limited in its impact, the addition of guided purposeful movement performed in a manner consistent with PNE may be vital to the desired behavioral changes, and when inconsistent messages are delivered between education and movement interventions, outcomes may be adversely impacted. PMID- 27356080 TI - Synthesis of a Potent Vinblastine: Rationally Designed Added Benign Complexity. AB - Many natural products, including vinblastine, have not been easily subjected to simplifications in their structures by synthetic means or modifications by late stage semisynthetic derivatization in ways that enhance their biological potency. Herein, we detail a synthetic vinblastine that incorporates added benign complexity (ABC), which improves activity 10-fold, and is now accessible as a result of advances in the total synthesis of the natural product. The compound incorporates designed added molecular complexity but no new functional groups and maintains all existing structural and conformational features of the natural product. It constitutes a member of an analogue class presently inaccessible by semisynthetic derivatization of the natural product, by its late-stage functionalization, or by biosynthetic means. Rather, it was accessed by synthetic means, using an appropriately modified powerful penultimate single-step vindoline catharanthine coupling strategy that proceeds with a higher diastereoselectivity than found for the natural product itself. PMID- 27356082 TI - Human milk intake in preterm infants and neurodevelopment at 18 months corrected age. AB - BACKGROUND: The effect of human milk intake on neurodevelopment in preterm infants is uncertain. METHODS: We analyzed data from 611 participants in the DHA for Improvement of Neurodevelopmental Outcomes study, enrolled at <=33 wk gestation from five Australian perinatal centers. The main exposures were (i) average daily human milk intake during the neonatal hospitalization and (ii) total duration of human milk intake before and after discharge. Outcomes were Bayley Scales of Infant Development, 2nd Edition Mental (MDI), and Psychomotor (PDI) Development Indexes. RESULTS: Adjusting for confounders in linear regression, human milk intake was not associated with higher MDI (0.2 points per 25 ml/kg/d; 95% confidence interval (CI): -0.6, 1.0) or PDI (-0.3 points; 95% CI: -1.1, 0.4). Longer duration of human milk intake was also not associated with MDI (0.1 points per month; 95% CI: -0.2, 0.3) or PDI (-0.2 points per month; 95% CI: 0.5, 0.01) scores, except in infants born 29-33 wk gestation (n = 364, MDI 0.3 points higher per additional month, 95% CI: 0.1, 0.6). CONCLUSIONS: We found no associations of human milk intake during the neonatal hospitalization with neurodevelopment at 18 mo corrected age. PMID- 27356081 TI - Altered cardiovascular function at birth in growth-restricted preterm lambs. AB - BACKGROUND: Cardiovascular dysfunction at birth may underlie poor outcomes after fetal growth restriction (FGR) in neonates. We compared the cardiovascular transition between FGR and appropriately grown (AG) preterm lambs and examined possible mechanisms underlying any cardiovascular dysfunction in FGR lambs. METHODS: FGR was induced in ewes bearing twins at 0.7 gestation; the twin was used as an internal control (AG). At 0.8 gestation, lambs were delivered and either euthanized with their arteries isolated for in vitro wire myography, or ventilated for 2 h. At 60 min, inhaled nitric oxide (iNO) was administered in a subgroup for 30 min. Molecular assessment of the nitric oxide (NO) pathway within lung tissue was conducted. RESULTS: FGR lambs had lower left ventricular output and cerebral blood flow (CBF) and higher systemic vascular resistance compared with AG lambs. INO administration to FGR lambs rapidly improved cardiovascular and systemic hemodynamics but resulted in decreased CBF in AG lambs. Isolated arteries from FGR lambs showed impaired sensitivity to NO donors, but enhanced vasodilation to Sildenafil and Sodium nitroprusside, and altered expression of components of the NO pathway. CONCLUSION: Cardiovascular dysfunction at birth may underlie the increased morbidity and mortality observed in preterm FGR newborns. Impaired NO signaling likely underlies the abnormal vascular reactivity. PMID- 27356083 TI - Early docosahexaenoic and arachidonic acid supplementation in extremely-low-birth weight infants. AB - BACKGROUND: Extremely-low-birth-weight (ELBW) infants accrue large deficits in docosahexaenoic acid (DHA) and arachidonic acid (ARA) and require improved supplementation strategies. We hypothesized that once daily DHA+ARA drops applied to buccal mucosa will increase blood levels. METHODS: Thirty ELBW infants were randomized to receive DHA 20 mg/kg/d + ARA 40 or 60 mg/kg/d + ARA 120 mg/kg/d or placebo within 72 h of age for 8 wk duration. Red blood cell phospholipid levels of DHA (primary) and ARA (secondary) were measured at 2 and 8 wk of age. RESULTS: Twenty-eight survivors with a median birth weight of 806 g completed dosing and sampling. Red blood cell levels were similar between the three groups at 2 wk (DHA: 4.62 wt% (interquartile range (IQR) 4.1-5.5) for all, P = 0.29 between groups; ARA: 21.1 wt% (IQR 18.78-22.6) for all, P = 0.41 between groups) and 8 wk (DHA: 6.0 wt% (IQR 5.1-7.1) for all, P = 0.57 between groups; ARA: 20.1 wt% (IQR 18.3-23.1) for all, P = 0.63 between groups). DHA in all infants showed a median increase of 31% from 2 to 8 wk (P < 0.04). ARA levels did not significantly change over time (P > 0.6). CONCLUSION: Daily buccal DHA and ARA supplements did not affect fatty acid levels in ELBW infants. PMID- 27356084 TI - Hippocampal volume reduction is associated with intellectual functions in adolescents with congenital heart disease. AB - BACKGROUND: Adolescents undergoing early cardiopulmonary bypass surgery for congenital heart disease (CHD) may demonstrate a variety of neurocognitive impairments. These impairments can affect overall intellectual functions, but also specific memory deficits, language, and executive functions. As the hippocampus is a critical structure involved in these functions, we sought to determine whether hippocampal volume was reduced in adolescents with CHD and whether altered volumes were related to functional outcome. METHODS: At a mean age of 13.8 y, 48 adolescent survivors of childhood cardiopulmonary bypass surgery for CHD and 32 healthy controls underwent neurocognitive testing and cerebral magnetic resonance imaging. Images were quantitatively analyzed using an automated regional segmentation tool (FSL-FIRST). RESULTS: Adolescents with CHD had 10% lower total hippocampal volumes compared with controls. After controlling for total brain volume, total hippocampal volume correlated with total IQ, with working memory, and verbal comprehension in CHD patients, but not in controls. CONCLUSIONS: In adolescent survivors of cardiopulmonary bypass surgery for CHD, specific brain regions such as the hippocampus may show long-term persistent alteration and correlate with intellectual deficits, particularly with verbal and memory functions. PMID- 27356086 TI - Associations between allergic diseases and attention deficit hyperactivity/oppositional defiant disorders in children. AB - BACKGROUND: We aim to investigate the detailed associations between allergic diseases with attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) among children. METHODS: Clinical information from 2,896 children enrolled in the Taiwan Children Health Study was obtained for analyses. Allergic diseases, including atopic dermatitis, asthma, and allergic rhinitis, have been evaluated based on the questions adjusted from International Study of Asthma and Allergies in Childhood. The Swanson, Nolan, and Pelham questionnaire was used to assess symptoms of ADHD and ODD. Symptoms of depression, stress, and poor sleep quality were evaluated as the interactive risk factors. RESULTS: Children having symptoms of allergic diseases within the past 1 y were associated with having all dimensions of symptoms of ADHD and ODD. Children with ever having a physician-diagnosed atopic dermatitis were associated with inattentive and hyperactive-impulsive symptoms of ADHD. Ever diagnosed asthma was associated with ADHD and ODD. Ever diagnosed allergic rhinitis was associated with inattentive and combined symptoms of ADHD and ODD. CONCLUSION: Children with allergic diseases, such as atopic dermatitis, asthma, and allergic rhinitis, were associated with exhibiting ADHD and ODD. PMID- 27356085 TI - Microarray gene expression analysis in ovine ductus arteriosus during fetal development and birth transition. AB - BACKGROUND: Patent ductus arteriosus (PDA) in the newborn is the most common congenital heart anomaly and is significantly more common in preterm infants. Contemporary pharmacological treatment is effective in only 70-80% of the cases. Moreover, indomethacin or ibuprofen, which are used to close a PDA may be accompanied by serious side effects in premature infants. To explore the novel molecular pathways, which may be involved in the maturation and closure of the ductus arteriosus (DA), we used fetal and neonatal sheep to test the hypothesis that maturational development of DA is associated with significant alterations in specific mRNA expression. METHODS: We conducted oligonucleotide microarray experiments on the isolated mRNA from DA and ascending aorta from three study groups (premature fetus-97 +/- 0 d, near-term fetus-136 +/- 0.8 d, and newborn lamb-12 +/- 0 h). We compared the alterations in mRNA expression in DA and aorta to identify genes specifically involved in DA maturation. RESULTS: Results demonstrate significant changes in wingless-integrin1, thrombospondin 1, receptor activator of nuclear factor-kappa B, nitric oxide synthase, and retinoic acid receptor activation signaling pathways. CONCLUSION: We conclude that these pathways may play an important role during both development and postnatal DA closure and warrant further investigation. PMID- 27356087 TI - Familial Recurrence of 3MC Syndrome in Consanguineous Families: A Clinical and Molecular Diagnostic Approach With Review of the Literature. AB - We report four individuals from two unrelated consanguineous families with 3MC syndrome. In the first family, chromosome microarray data revealed that the two affected sisters, born to first-cousin parents, shared a unique homozygous C terminal deletion in the COLEC11 gene. Two affected brothers from a second family, also born to first-cousin parents, shared a region of homozygosity that included the second gene known to cause the 3MC syndrome, MASP1. We discuss the diagnostic approach of craniofacial disorders born to consanguineous parents and highlight a literature search and reference a helpful dysmorphology solution powered by FDNA (Facial Dysmorphology Novel Analysis) technology. PMID- 27356088 TI - Fragile X tremor ataxia syndrome and white matter dementia. AB - OBJECTIVE: Fragile X tremor ataxia syndrome (FXTAS) is an inherited neurodegenerative disease in which dementia is common and disabling. The pathogenesis of dementia in FXTAS is poorly understood, but the salience of executive dysfunction and slowed processing speed, the frequent presence of the middle cerebellar peduncle sign on magnetic resonance imaging (MRI), and striking neuropathological alterations of white matter all suggest that myelinated tracts are significantly involved. This paper considers the role of white matter disease in FXTAS dementia, particularly with regard to the concept of white matter dementia (WMD). METHOD: A focused review of FXTAS in relation to known white matter disorders is provided to propose that the concept of WMD may illuminate the basis of dementia in FXTAS. The putative pathogenetic contribution of white matter involvement in other neurodegenerative diseases is also considered. RESULTS: Considerable evidence supports the importance of white matter disease in the pathogenesis of dementia in FXTAS. Whereas, gray matter regions are also involved, white matter degeneration is prominent, even early in the disease, and correlates with executive dysfunction and slowed processing speed. Evidence for white matter involvement in other neurodegenerative diseases lends additional support to the relevance of white matter in FXTAS. CONCLUSION: The dementia of FXTAS is closely related to the profile of WMD, and white matter involvement is also supported by MRI and neuropathological observations. White matter pathology is also relevant to the pathogenesis of other neurodegenerative diseases. Further study of white matter promises to clarify the origin of dementia in FXTAS. PMID- 27356089 TI - Electroconvulsive Therapy in a Patient With Chronic Catatonia: Clinical Outcomes and Cerebral 18[F]Fludeoxyglucose Positron Emission Tomography Findings. AB - Catatonia is a psychomotor syndrome that can be associated with both psychiatric diseases (mainly mood disorders, but also psychotic disorders) and medical conditions. Lorazepam (6-21 mg/day, occasionally up to 30 md/day) is the first choice treatment and electroconvulsive therapy (ECT) is the second line, regardless of the underlying clinical condition. There are some evidences also for effectiveness of other medications. Patients treated acutely usually show rapid and full therapeutic response but even longstanding catatonia can improve. However, some authors suggested that chronic catatonia in the context of schizophrenia is phenomenologically different and less responsive to lorazepam and ECT, especially if associated with echophenomena. We present here the case of a patient with longstanding catatonic schizophrenia treated with antipsychotics who significantly improved after ECT. Improvement regarded mainly catatonia, but also negative symptoms, cognition and psychosocial functioning. A slight amelioration in prefrontal metabolism (Brain[F]FDG PET) one month following the ECT course was also noted. PMID- 27356090 TI - Luteinising hormone releasing hormone (LHRH) agonists for the treatment of relapsed epithelial ovarian cancer. AB - BACKGROUND: Ovarian cancer is seventh most common cancer in women worldwide. Approximately 1.3% of women will be diagnosed with ovarian cancer at some point during their life time. The majority of tumours arise from surface of the ovary (epithelial). Two thirds of these women will present with advanced disease, requiring aggressive treatment, which includes debulking surgery (removal of as much disease as possible) and chemotherapy. However, most women (75%) with advanced epithelial ovarian cancer (EOC) will relapse following surgery and chemotherapy. Patients who relapse are treated with either platinum or non platinum drugs and this is dependent on the platinum-sensitivity and platinum free interval. These drug regimens are generally well-tolerated although there are potential severe side effects. New treatments that can be used to treat recurrence or prevent disease progression after first-line or subsequent chemotherapy are important, especially those with a low toxicity profile. Hormones such as luteinising hormone releasing hormone (LHRH) agonists have been used in the treatment of relapsed EOC. Some studies have shown objective remissions, while other studies have shown little or no benefit. Most small studies report a better side-effect profile for LHRH agonists when compared to standard chemotherapeutic agents used in EOC. OBJECTIVES: To compare the effectiveness and safety of luteinising hormone releasing hormone (LHRH) agonists with chemotherapeutic agents or placebo in relapsed epithelial ovarian cancer (EOC). SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group trials register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase up to January 2016. We also searched registers of clinical trials and abstracts of scientific meetings. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared LHRH agonists with chemotherapeutic agents or placebo in relapsed EOC. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether relevant studies met the inclusion criteria, retrieved data and assessed risk of bias. MAIN RESULTS: Two studies, including 97 women, met our inclusion criteria: one assessed LHRH agonist (leuprorelin) use in relapsed (platinum-resistant and platinum-refractory) EOC in comparison with a chemotherapeutic agent (treosulfan) (Du Bois 2002); the other examined LHRH agonist (decapeptyl) versus a placebo (Currie 1994). Since both studies had different control groups, a meta-analysis was not possible.There may be little or no difference between treatment with leuprorelin or treosulfan in overall survival (OS) (hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.58 to 1.67; very low-quality evidence) or progression-free survival (PFS) at six and 12 months (risk ratio (RR) 0.61, 95% CI 0.22 to 1.68, and RR 0.65, 95% CI 0.12 to 3.66; very low-quality evidence), respectively (Du Bois 2002). The duration of follow-up was 2.5 years and quality of life (QoL) was not reported in this study.Alopecia and fatigue were probably more common with treosulfan than leuprorelin (alopecia RR 0.32, 95% CI 0.12 to 0.91 (very low-quality evidence)). There may be little or no difference in other Grade 3/4 side effects: nausea and vomiting (RR 0.65, 95% CI 0.12 to 3.66 (very low-quality evidence)); neurotoxicity (RR 0.32, 95% CI 0.01 to 7.71 (very low-quality evidence)) and neutropenia (RR 0.97, 95% 0.06 to 14.97 (very low-quality evidence)),The Currie 1994 study, which compared decapeptyl treatment with placebo, reported mean PFS of 16 weeks verus 11.2 weeks, respectively. No relative effects measures or P value at a particular time point were reported. Overall survival (OS) and QoL outcomes were not reported. In addition, adverse events were only mentioned for the decapeptyl group.Adverse events were incompletely reported (no adverse events in decapeptyl group, but not reported for the placebo group). AUTHORS' CONCLUSIONS: Based on this review of two small RCTs, there is not enough evidence to comment on the safety and effectiveness of LHRH agonists in the treatment of platinum-refractory and platinum-resistant (relapsed) EOC. Overall, the quality of evidence for all outcomes (including OS, PFS, QoL and adverse events) is very low. PMID- 27356091 TI - Supramolecular Control over Split-Luciferase Complementation. AB - Supramolecular split-enzyme complementation restores enzymatic activity and allows for on-off switching. Split-luciferase fragment pairs were provided with an N-terminal FGG sequence and screened for complementation through host-guest binding to cucurbit[8]uril (Q8). Split-luciferase heterocomplex formation was induced in a Q8 concentration dependent manner, resulting in a 20-fold upregulation of luciferase activity. Supramolecular split-luciferase complementation was fully reversible, as revealed by using two types of Q8 inhibitors. Competition studies with the weak-binding FGG peptide revealed a 300 fold enhanced stability for the formation of the ternary heterocomplex compared to binding of two of the same fragments to Q8. Stochiometric binding by the potent inhibitor memantine could be used for repeated cycling of luciferase activation and deactivation in conjunction with Q8, providing a versatile module for in vitro supramolecular signaling networks. PMID- 27356092 TI - Acredinone C and the Effect of Acredinones on Osteoclastogenic and Osteoblastogenic Activity. AB - A new inhibitor, acredinone C (1), of receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation was isolated from the culture broth of the fungus Acremonium sp. (F9A015) along with acredinones A (2) and B (3). The structure of acredinone C (1), which incorporates benzophenone and xanthone moieties, was established by the analyses of combined spectroscopic data including 1D and 2D NMR and MS. All of the acredinones studied efficiently inhibited the RANKL-induced formation of TRAP(+)-MNCs in a dose-dependent manner without any cytotoxicity up to 10 MUM. Acredinone A showed dual activity in both osteoclast and osteoblast differentiation in vitro and good efficacy in an animal disease model of bone formation. PMID- 27356093 TI - Synthesis of Diversely Functionalized Oxindoles Enabled by Migratory Insertion of Isocyanide to a Transient sigma-Alkylpalladium(II) Complex. AB - Palladium-catalyzed intramolecular carbopalladation of N-aryl acrylamides followed by migratory insertion of an isocyanide-coordinated C(sp(3) )-Pd intermediate afforded an alkylimidoyl-Pd(II) complex, which can be intercepted by a nucleophile, including heteroarenes. In addition to amides, the alkylimidoyl Pd(II) complex was successfully converted into esters, ketones, and bis heterocyclic compounds. An unprecedented palladium-catalyzed enantioselective domino process involving isocyanide was also documented. PMID- 27356094 TI - Amphiphilic dendritic nanomicelle-mediated co-delivery of 5-fluorouracil and doxorubicin for enhanced therapeutic efficacy. AB - Combination cancer therapy has attracted considerable attention due to its enhanced antitumor efficacy and reduced toxicity granted by synergistic effects over monotherapy. The application of nanotechnology is expected to achieve coencapsulation of multiple anticancer agents with enhanced therapeutic efficacy. Herein, a unique nanomicelle based on amphiphilic dendrimer (AmD) consisting of a hydrophilic polyamidoamine dendritic shell and a hydrophobic polylactide core is developed for effectively loading and shuttling 5-fluorouracil (5-Fu) and doxorubicin (Dox). The yielded drug-encapsulated dendritic nanomicelle (5-Fu/Dox DNM) has a modest average size of 68.6 +/- 3.3 nm and shows pH-sensitive drug release manner. The parallel activity of 5-Fu and Dox show synergistic anticancer efficacy. The IC50 value of 5-Fu/Dox-DNM toward human breast cancer (MDA-MB-231) cells was 0.25 MUg/mL, presenting an 11.2-fold and 6.1-fold increase in cytotoxicity compared to Dox-DNM and 5-Fu-DNM, respectively. Furthermore, 5 Fu/Dox-DNM significantly inhibits the progression of tumor growth in the MDA-MB 231 xenograft tumor mice model. In conclusion, we have demonstrated that our AmD based combination therapeutic system has promising potential to open an avenue for coencapsulation of multiple chemotherapeutic agents to promote superior anticancer effect. PMID- 27356096 TI - Asymmetric Syntheses of (-)-ADMJ and (+)-ADANJ: 2-Deoxy-2-amino Analogues of (-) 1-Deoxymannojirimycin and (+)-1-Deoxyallonojirimycin. AB - The asymmetric syntheses of (-)-ADMJ and (+)-ADANJ, the 2-deoxy-2-amino analogues of (-)-1-deoxymannojirimycin and (+)-1-deoxyallonojirimycin, are described herein. Methodology for the ring-closing iodoamination of bishomoallylic amines followed by in situ ring-expansion (via intramolecular ring-opening of the corresponding aziridinium intermediates with a tethered carbamate moiety) to give oxazolidin-2-ones was initially optimized on a model system. Subsequent application of this methodology to two enantiopure bishomoallylic amines (which were produced via aminohydroxylation of an alpha,beta-unsaturated ester, partial reduction, and reaction of the corresponding aldehyde with vinylmagnesium bromide) also proceeded with concomitant N-debenzylation to afford the corresponding diastereoisomerically pure (>99:1 dr) oxazolidin-2-ones. Subsequent deprotection of these enantiopure templates gave (-)-ADMJ and (+)-ADANJ as single diastereoisomers in 16% and 24% overall yield, respectively. PMID- 27356095 TI - EPI-001, A Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor. AB - Castration-resistant prostate cancer is the lethal condition suffered by prostate cancer patients that become refractory to androgen deprivation therapy. EPI-001 is a recently identified compound active against this condition that modulates the activity of the androgen receptor, a nuclear receptor that is essential for disease progression. The mechanism by which this compound exerts its inhibitory activity is however not yet fully understood. Here we show, by using high resolution solution nuclear magnetic resonance spectroscopy, that EPI-001 selectively interacts with a partially folded region of the transactivation domain of the androgen receptor, known as transactivation unit 5, that is key for the ability of prostate cells to proliferate in the absence of androgens, a distinctive feature of castration-resistant prostate cancer. Our results can contribute to the development of more potent and less toxic novel androgen receptor antagonists for treating this disease. PMID- 27356098 TI - Mismatch discrimination of lipidated DNA and LNA-probes (LiNAs) in hybridization controlled liposome assembly. AB - Assays for mismatch discrimination and detection of single nucleotide variations by hybridization-controlled assembly of liposomes, which do not require tedious surface chemistry, are versatile for both DNA and RNA targets. We report herein a comprehensive study on different DNA and LNA (locked nucleic acids) probe designs, including membrane-anchoring requirements, studies on different probes and target lengths (including overhangs), DNA and RNA targets (including sequences associated with pathogens) for lipidated nucleic acids (LiNAs). Advantages and limitations of the liposome assembly based assay in the context of mismatch discrimination and SNP detection are presented. The advantages of membrane-anchored LiNA-probes compared to chemically attached probes on solid nanoparticles (e.g. gold nanoparticles) are described. Key functionalities such as non-covalent attachment of LiNA probes without the need for long spacers and the inherent mobility of membrane-anchored probes in lipid-bilayer membranes will be described for several different probe designs. PMID- 27356097 TI - Missense splice variant (g.20746A>G, p.Ile183Val) of interferon gamma receptor 1 (IFNGR1) coincidental with mycobacterial osteomyelitis - a screen of osteoarticular lesions. AB - Previously, dominant partial interferon-gamma receptor 1 (IFN-g-R1) susceptibility to environmental mycobacteria was found with IFNGR1 deletions or premature stop. Our aim was to search for IFNGR1 variants in patients with mycobacterial osteoarticular lesions. Biopsies from the patients were examined for acid-fast bacilli, inflammatory cell infiltration, and mycobacterial niacin. Mycobacterial rRNA was analyzed using a target-amplified rRNA probe test. Peripheral-blood-leukocyte genomic DNA was isolated from 19 patients using the QIAamp DNA Mini Kit, and all IFNGR1 exons were sequenced using an ABIPRISM 3130 device. After the discovery of an exon 5 variant, a Polish newborn population sample (n = 100) was assayed for the discovered variant. Splice sites and putative amino acid interactions were analyzed. All patients tested were positive for mycobacteria; one was heterozygous for the IFNGR1 exon 5 single-nucleotide missense substitution (g.20746A>G, p.Ile183Val). No other variant was found. The splice analysis indicated the creation of an exonic splicing silencer, and alternatively, molecular graphics indicated that the p.Ile183Val might alter beta strand packing (loss of van der Waals contacts; Val183/Pro205), possibly altering the IFN-g-R1/IFN-g-R2 interaction. The probability of non-deleterious variant was estimated as <10%. Heterozygous IFNGR1:p.Ile183Val (frequency 0.003%) was found to be coincidental with mycobacterial osteomyelitis. The small amount of variation detected in the patients with osteoarticular lesions indicates that screens should not yet be restricted: Intronic variants should be analyzed as well as the other genes affecting Type 1 T-helper-cell-mediated immunity. PMID- 27356099 TI - Decay behavior of screened electrostatic surface forces in ionic liquids: the vital role of non-local electrostatics. AB - Screened electrostatic surface forces, also called double layer forces, between surfaces in ionic liquids can, depending on the circumstances, decay in an exponentially damped, oscillatory manner or in a plain exponential way (the latter as in dilute electrolyte solutions where ion-ion correlations are very weak). The occurrence of both of these behaviors in dense ionic liquids, where ion-ion correlations are very strong, is analyzed in the current work using exact statistical mechanics formulated in a manner that is physically transparent. A vital ingredient in understanding the decay behaviors is the fact that electrostatics in dense electrolytes have a non-local nature caused by the strong correlations. It is shown that the effects of non-locality can be elucidated by a remarkably simple, general expression for the decay parameter kappa that replaces the classical expression for the inverse Debye length kappaDH of the Debye-Huckel (DH) and non-linear Poisson-Boltzmann approximations. This exact expression is valid for both the plain exponential and the oscillatory cases. It shows how strong correlations can give rise to plain exponential decay with a long decay length. Such a decay can arise from anion-cation associations of various kinds, for instance transient ion pairing or association caused by many-body correlations; ion pairing is a possibility but not a necessity for this to occur. Theoretical analysis is done for systems consisting of ions with an arbitrary shape and internal charge density and immersed planar walls with arbitrary internal charge distribution and any short-range ion-surface interaction. The screened electrostatic surface force between two walls is at large separations proportional to the product of effective surface charge densities of each wall. For the oscillatory case, each wall contributes with a phase shift to the oscillations of the interaction. PMID- 27356101 TI - WO3-x Nanoplates Grown on Carbon Nanofibers for an Efficient Electrocatalytic Hydrogen Evolution Reaction. AB - The search for non-noble metal catalysts with high activity for the hydrogen evolution reaction (HER) is crucial for efficient hydrogen production at low cost and on a large scale. Herein, we report a novel WO3-x catalyst synthesized on carbon nanofiber mats (CFMs) by electrospinning and followed by a carbonization process in a tubal furnace. The morphology and composition of the catalysts were tailored via a simple method, and the hybrid catalyst mats were used directly as cathodes to investigate their HER performance. Notably, the as-prepared catalysts exhibit substantially enhanced activity for the HER, demonstrating a small overpotential, a high exchange current density, and a large cathodic current density. The remarkable electrocatalytic performances result from the poor crystallinity of WO3-x, the high electrical conductivity of WO3-x, and the use of electrospun CNFs. The present work outlines a straightforward approach for the synthesis of transition metal oxide (TMO)-based carbon nanofiber mats with promising applications for the HER. PMID- 27356100 TI - Kinetics of the Interactions between Copper and Amyloid-beta with FAD Mutations and Phosphorylation at the N terminus. AB - Mutations and post-translational modifications of amyloid-beta (Abeta) peptide in its N terminus have been shown to increase fibril formation, yet the molecular mechanism is not clear. Here we investigated the kinetics of the interactions of copper with two Abeta peptides containing Familial Alzheimer's disease (FAD) mutations (English (H6R) and Tottori (D7N)), as well as with Abeta peptide phosphorylated at serine 8 (pS8). All three peptides bind to copper with a similar rate as the wild-type (wt). The dissociation rates follow the order pS8>H6R>wt>D7N; the interconversion between the two coordinating species occurs 50 % faster for H6R and pS8, whereas D7N had only a negligible effect. Interestingly, the rate of ternary complex (copper-bridged heterodimer) formation for the modified peptides was significantly faster than that for wt, thus leading us to propose that FAD and sporadic AD might share a kinetic origin for the enhanced oligomerisation of Abeta. PMID- 27356102 TI - No evidence for metabolic adaptation in thermic effect of food by dietary protein. AB - OBJECTIVE: Determine whether prolonged consumption of high- or low-protein diets modifies the thermogenic response to a standard meal. METHODS: Twenty-four healthy individuals were randomized to overfeeding diets containing low (5%, n = 8), normal (15%, n = 9), or high (25%, n = 7) protein for 56 days while inpatients. The thermic effect of food (TEF) was measured over 4 h by indirect calorimetry following a standard meal (20% of energy, 20% protein) or a meal that matched the study diet ("study meal"). RESULTS: As expected, the TEF following the study meal (i.e., either low, normal, or high protein content) was significantly associated with dietary protein (P = 0.007), and the TEF was significantly increased in the high-protein diet (15.4%) versus the normal protein (5.6%) and low-protein diets (6.4%) (P = 0.05 and P = 0.03, respectively). However, returning to a standard meal (20% protein) after 42 days of overfeeding the study diets, the TEF response did not differ from baseline between groups or within subjects regardless of the prolonged intake of the habitual study diet (high protein: P = 0.32, low protein: P = 0.11, normal protein: P = 0.79). CONCLUSIONS: TEF is related to acute dietary protein intake but not altered by prolonged intake of high-energy diets with high or low protein content. PMID- 27356103 TI - What Motivates Users to Continue Using Diet and Fitness Apps? Application of the Uses and Gratifications Approach. AB - This study explored how the gratifications obtained from the use of diet and fitness apps may motivate users to continue their use of these apps. The effects of seven gratifications obtained were analyzed through hierarchical regression analyses. Results showed that the five gratifications of recordability, networkability, credibility, comprehensibility, and trendiness significantly predicted user intention to continue using diet/fitness apps; the hypothesized gratifications of accuracy and entertainment were not significant predictors. These findings contribute to broadening our theoretical and practical knowledge of new digital, mobile media phenomena by identifying use motivations specific to diet/fitness apps. Based on the findings, recommendations for researchers, practitioners, and developers are provided. PMID- 27356105 TI - Resistance is not futile: Surviving Eg5 inhibition. PMID- 27356106 TI - Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia. AB - Neonatal asphyxia can cause irreversible injury of multiple organs resulting in hypoxic-ischemic encephalopathy and necrotizing enterocolitis (NEC). This injury is dependent on time, severity, and gestational age, once the preterm babies need ventilator support. Our aim was to assess the different brain and intestinal effects of ischemia and reperfusion in neonate rats after birth anoxia and mechanical ventilation. Preterm and term neonates were divided into 8 subgroups (n=12/group): 1) preterm control (PTC), 2) preterm ventilated (PTV), 3) preterm asphyxiated (PTA), 4) preterm asphyxiated and ventilated (PTAV), 5) term control (TC), 6) term ventilated (TV), 7) term asphyxiated (TA), and 8) term asphyxiated and ventilated (TAV). We measured body, brain, and intestine weights and respective ratios [(BW), (BrW), (IW), (BrW/BW) and (IW/BW)]. Histology analysis and damage grading were performed in the brain (cortex/hippocampus) and intestine (jejunum/ileum) tissues, as well as immunohistochemistry analysis for caspase-3 and intestinal fatty acid-binding protein (I-FABP). IW was lower in the TA than in the other terms (P<0.05), and the IW/BW ratio was lower in the TA than in the TAV (P<0.005). PTA, PTAV and TA presented high levels of brain damage. In histological intestinal analysis, PTAV and TAV had higher scores than the other groups. Caspase-3 was higher in PTAV (cortex) and TA (cortex/hippocampus) (P<0.005). I-FABP was higher in PTAV (P<0.005) and TA (ileum) (P<0.05). I-FABP expression was increased in PTAV subgroup (P<0.0001). Brain and intestinal responses in neonatal rats caused by neonatal asphyxia, with or without mechanical ventilation, varied with gestational age, with increased expression of caspase-3 and I-FABP biomarkers. PMID- 27356108 TI - Epidemiological study of power lines and childhood cancer in the UK: further analyses. AB - We report further analyses from an epidemiological study of childhood cancer and residence at birth near high-voltage power lines in the UK. These results suggest that the elevated risks for childhood leukaemia that we previously found for overhead power lines may be higher for older age at diagnosis and for myeloid rather than lymphoid leukaemia. There are differences across regions of birth but not forming any obvious pattern. Our results suggest the decline in risk we previously reported from the 1960s to the 2000s is linked to calendar year of birth or of cancer occurrence rather than the age of the power lines concerned. Finally, we update our previous analysis of magnetic fields to include later subjects. PMID- 27356109 TI - Inhibitory effect of gamma irradiation and its application for control of postharvest green mold decay of Satsuma mandarins. AB - Gamma irradiation has been shown to be effective for the control of postharvest fungi in vitro, but little is known regarding antifungal action, responses to gamma irradiation, and its application to fresh produce. Gamma irradiation was evaluated for its in vitro and in vivo antifungal activity against Penicillium digitatum on Satsuma mandarin fruits. Green mold was inhibited in a dose dependent manner. Gamma irradiation showed a complete inhibition of spore germination, germ tube elongation, and mycelial growth of P. digitatum, particularly at 1.0kGy. To further investigate the mechanisms by which gamma irradiation inhibits fungal growth, the membrane integrity and cellular leakage of conidia were tested, indicating that gamma irradiation results in the loss of plasma membrane integrity, causing the release of intracellular contents such as soluble proteins. In vivo assays demonstrated that established doses can completely inhibit the growth of fungal pathogens, but such high doses cause severe fruit damage. Thus, to eliminate the negative impact on fruit quality, gamma irradiation at lower doses was evaluated for inhibition of P. digitatum, in combination with a chlorine donor, sodium dichloro-s-triazinetrione (NaDCC). Interestingly, only a combined treatment with 0.4kGy of gamma irradiation and 10ppm of NaDCC exhibited significant synergistic antifungal activity against green mold decay. The mechanisms by which the combined treatment decreased the green mold decay of mandarin fruits can be directly associated with the disruption of cell membrane of the fungal pathogen, which resulted in a loss of cytoplasmic material from the hyphae. These findings suggest that a synergistic effect of combining treatment with gamma irradiation with NaDCC has potential as an antifungal approach to reduce the severity of green mold in mandarin fruits. PMID- 27356107 TI - Predictors of early treatment discontinuation and severe anemia in a Brazilian cohort of hepatitis C patients treated with first-generation protease inhibitors. AB - The aim of this study was to determine risk factors for adverse events (AE) related treatment discontinuation and severe anemia among patients with chronic hepatitis C virus (HCV) genotype 1 infection, treated with first-generation protease inhibitor (PI)-based therapy. We included all patients who initiated treatment with PI-based therapy at a Brazilian university hospital between November 2013 and December 2014. We prospectively collected data from medical records using standardized questionnaires and used Epi Info 6.0 for analysis. Severe anemia was defined as hemoglobin <=8.5 mg/dL. We included 203 patients: 132 treated with telaprevir (TVR) and 71 treated with boceprevir (BOC). AE related treatment discontinuation rate was 19.2% and anemia was the main reason (38.5%). Risk factors for treatment discontinuation were higher comorbidity index (OR=1.85, CI=1.05-3.25) for BOC, and higher bilirubin count (OR=1.02, CI=1.01 1.04) and lower BMI (OR=0.98, CI=0.96-0.99) for TVR. Severe anemia occurred in 35 (17.2%) patients. Risk factors for this outcome were lower estimated glomerular filtration rate (eGFR; OR=0.95, CI=0.91-0.98) for patients treated with TVR, and higher comorbidity index (OR=2.21, CI=1.04-4.67) and ribavirin dosage (OR=0.84, CI=0.72-0.99) for those treated with BOC. Fifty-five (57.3%) patients treated with TVR and 15 (27.3%) patients treated with BOC achieved sustained virological response (SVR). Among patients who received TVR and interrupted treatment due to AE (n=19), only 26.3% (n=5) achieved SVR (P=0.003). Higher number of comorbidities, lower eGFR and advanced liver disease are associated with severe anemia and early treatment cessation, which may compromise SVR achievement. PMID- 27356110 TI - Physician-Industry Interactions and Anti-Vascular Endothelial Growth Factor Use Among US Ophthalmologists. AB - IMPORTANCE: The publication of the US Physician Payments Sunshine Act provides insight into the financial relationship between physicians and the pharmaceutical industry. This added transparency creates new opportunities of using objective data to better understand prior research that implicates pharmaceutical promotions as an important factor in a physician's decision-making process. OBJECTIVE: To assess the association between reported industry payments and physician-prescribing habits by comparing the use of anti-vascular endothelial growth factor (VEGF) intravitreal injections by US ophthalmologists to the industry payments these same physicians received. DESIGN, SETTING, PARTICIPANTS: This study reviews data from the Centers for Medicare & Medicaid Services (CMS) 2013 Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File and the CMS-sponsored August through December 2013 Open Payments program (Physician Payments Sunshine Act). Ophthalmologists who prescribe anti VEGF injections for all indications were analyzed. MAIN OUTCOMES AND MEASURES: Association between industry payments reportedly received and the number and type of anti-VEGF injections administered. RESULTS: A total of 3011 US ophthalmologists were reimbursed by CMS for 2.2 million anti-VEGF injections in 2013. Of these physicians, 38.0% reportedly received $1.3 million in industry payments for ranibizumab and aflibercept. Analysis revealed positive associations between increasing numbers of reported industry payments and total injection use (r = 0.24; 95% CI, 0.22-0.26; P < .001), aflibercept and ranibizumab injection use (r = 0.32; 95% CI, 0.29-0.34; P < .001), and percentage of injections per physician that were aflibercept or ranibizumab (r = 0.27; 95% CI, 0.25-0.29; P < .001). A smaller association was noted between greater number of industry payments and bevacizumab injection use (r = 0.07; 95% CI, 0.04-0.09; P < .001). Similar associations were found between the total dollars of reported industry payments received to injection use. Subgroup analysis further revealed that physicians receiving $1 to $25 in reported industry benefits were more likely than those not receiving industry payments to perform a greater percentage of their injections with aflibercept and ranibizumab. CONCLUSIONS AND RELEVANCE: Among ophthalmologists who prescribe anti-VEGF medications, there is a positive association between reported pharmaceutical payments and increased use of aflibercept and ranibizumab injections. As is inherent to the design of correlation studies, this analysis cannot determine whether the payments reported caused the increased use, are a result of the increased use, or are merely associated with some other factor that causes the increased use. PMID- 27356111 TI - Local influence diagnostics for hierarchical count data models with overdispersion and excess zeros. AB - We consider models for hierarchical count data, subject to overdispersion and/or excess zeros. Molenberghs et al. () and Molenberghs et al. () extend the Poisson normal generalized linear-mixed model by including gamma random effects to accommodate overdispersion. Excess zeros are handled using either a zero inflation or a hurdle component. These models were studied by Kassahun et al. (). While flexible, they are quite elaborate in parametric specification and therefore model assessment is imperative. We derive local influence measures to detect and examine influential subjects, that is subjects who have undue influence on either the fit of the model as a whole, or on specific important sub vectors of the parameter vector. The latter include the fixed effects for the Poisson and for the excess-zeros components, the variance components for the normal random effects, and the parameters describing gamma random effects, included to accommodate overdispersion. Interpretable influence components are derived. The method is applied to data from a longitudinal clinical trial involving patients with epileptic seizures. Even though the data were extensively analyzed in earlier work, the insight gained from the proposed diagnostics, statistically and clinically, is considerable. Possibly, a small but important subgroup of patients has been identified. PMID- 27356113 TI - Synthesis and Quantum Mechanical Studies of a Highly Stable Ferrocene Incorporated Expanded Porphyrin. AB - We present the first evidence for an unusual stable metallocene-containing expanded porphyrinoid macrocycle that was synthesized by condensing one equivalent of 1,1'-bis[phenyl(2-pyrroyl)methyl]ferrocene with one equivalent of 5,10-di(p-tolyl)-16-oxa-15,17-dihydrotripyrrane under acid-catalyzed conditions. The formation of ferrocene-incorporated expanded porphyrin macrocycle was confirmed by HR-MS and 1D/2D NMR spectroscopy. The macrocycle was nonaromatic and displayed absorption bands in the region of 420-550 nm. The molecular and electronic structure of the ferrocene-incorporated expanded porphyrin was investigated by DFT methods. The DFT calculations indicated a partially twisted structure of the molecule, and the extent of torsional distortion was larger than previously observed for ruthenocenoporphyrinoids and ferrocenothiaporphyrin. The HOMO and LUMO states that were obtained from the DFT calculations indicated partial charge density on all four pyrrole nitrogen atoms and the furanyl oxygen atom in the HOMO state and partial charge density on the alpha and beta carbon atoms in the LUMO state. In addition, the ferrocene moiety displayed the presence of partial charge density on the Fe atom and the cp rings in both the HOMO and LUMO states. Moreover, DFT studies of the diprotonated form of macrocycle indicated that the diprotonated form also retained a synclinal conformation and that its torsional strain was slightly higher than its free base form. PMID- 27356114 TI - Bioinspired Graphene-Based Nanocomposites and Their Application in Flexible Energy Devices. AB - Graphene is the strongest and stiffest material ever identified and the best electrical conductor known to date, making it an ideal candidate for constructing nanocomposites used in flexible energy devices. However, it remains a great challenge to assemble graphene nanosheets into macro-sized high-performance nanocomposites in practical applications of flexible energy devices using traditional approaches. Nacre, the gold standard for biomimicry, provides an excellent example and guideline for assembling two-dimensional nanosheets into high-performance nanocomposites. This review summarizes recent research on the bioinspired graphene-based nanocomposites (BGBNs), and discusses different bioinspired assembly strategies for constructing integrated high-strength and toughness graphene-based nanocomposites through various synergistic effects. Fundamental properties of graphene-based nanocomposites, such as strength, toughness, and electrical conductivities, are highlighted. Applications of the BGBNs in flexible energy devices, as well as potential challenges, are addressed. Inspired from the past work done by the community a roadmap for the future of the BGBNs in flexible energy device applications is depicted. PMID- 27356115 TI - Obesity: definition, comorbidities, causes, and burden. AB - Body mass index of 30 kg/m2 or higher is used to identify individuals with obesity. In the last 3 decades, the worldwide prevalence of obesity has increased 27.5% for adults and 47.1% for children. Obesity is the result of complex relationships between genetic, socioeconomic, and cultural influences. Consumption patterns, urban development, and lifestyle habits influence the prevalence of obesity. The condition may be the result of disease or pharmacologic treatment. It may also be a risk factor for the development of comorbid conditions. Persons who are obese have less school attendance, reduced earning potential, and higher healthcare costs that may result in an economic burden on society. A review of the prevalence and economic consequences of obesity is provided. Potential causes and comorbidities associated with obesity are also discussed. PMID- 27356116 TI - Overweight and obesity management strategies. AB - Comprehensive lifestyle interventions, including nutrition, physical activity, and behavioral therapy, are the foundation for clinical obesity management. New tools and treatment approaches help clinicians provide these interventions and support weight management in the primary care setting. Escalating treatment, such as using pharmacotherapy, medical devices, or bariatric surgery, are important considerations for appropriate patients who do not respond to lifestyle counseling. This article provides a review of obesity treatment in primary care and managed care settings. Principles of lifestyle changes for weight management, behavioral counseling, and options for pharmacotherapy, medical devices, and bariatric surgery are discussed. PMID- 27356117 TI - The role of managed care organizations in obesity management. AB - In the United States, obesity is characterized as this century's greatest healthcare threat. The American Medical Association and several other large organizations now classify obesity as a disease. Several federal initiatives are in the planning stages, have been approved, or are being implemented to address the disease. Obesity poses challenges for all healthcare stakeholders. Diet and exercise often are insufficient to create the magnitude of change patients and their attending healthcare providers need. Managed care organizations (MCOs) have 3 tools that can help their members: health and wellness programs focusing on lifestyle changes, prescription weight-loss drugs, and bariatric surgical interventions. MCOs are addressing changes with national requirements and are responding to the availability of new weight-loss drugs to help their members achieve better health. A number of factors either deter or stimulate the progress of weight loss therapy. Understanding how MCOs are key to managing obesity at the local level is important for healthcare providers. It can help MCOs and individual healthcare providers develop and coordinate strategies to educate stakeholders and better manage overall care. PMID- 27356118 TI - Re: Inclusion of Sexual Orientation and Gender Identity in Stage 3 Meaningful Use Guidelines: A Huge Step Forward for LGBT Health, by Cahill et al. (LGBT Health 2016;3:100-102). PMID- 27356119 TI - Parental Divorce or Death During Childhood and Adolescence and Its Association With Mental Health. AB - Despite the severity of the loss of a parent and the frequency of parental divorce, few studies compared their impact on mental health in the general adult population. The aim of this study was to estimate the prevalence, sociodemographic correlates, and psychiatric comorbidity of parental loss and parental divorce during childhood and adolescence. Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative sample of US adults (n = 43,093). Of the 43,093 participants, parental divorce during childhood or adolescence was reported by 5776 participants, whereas 3377 experienced parental death during childhood or adolescence. Participants reporting a history of parental divorce present a significantly higher prevalence of psychiatric disorders, particularly alcohol and drug use disorders compared with control subjects. While participants experiencing the death of a parent reported a poorer overall health, the prevalence of psychiatric disorder after 17 years of age was not significantly higher than that of the control subjects. PMID- 27356120 TI - Cluster B Personality Disorder Traits as a Predictor of Therapeutic Alliance Over Time in Residential Treatment for Substance Use Disorders. AB - While poor therapeutic alliance is a robust predictor of poor outcome in substance abuse treatment, less is known about the barriers to therapeutic alliances in this group. To explore this issue, this study examined whether the severity of cluster B personality disorders predicted therapeutic alliances concurrently and prospectively in a residential substance treatment program for homeless veterans. Participants were 48 adults with a substance abuse disorder. Personality disorder traits were assessed using the Structured Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Personality Disorders, whereas therapeutic alliance was assessed at baseline using the Working Alliance Inventory. Partial correlations controlling for overall symptom severity measured with the Symptom Checklist 90 and education, revealed cluster B traits at baseline predicted all 4 assessments of therapeutic alliance even after controlling for initial levels of therapeutic alliance. Results suggest that higher levels of cluster B traits are a barrier to the formation of working alliances in residential substance treatment. PMID- 27356121 TI - The Dark Side of Addiction: The Horsley Gantt to Joseph Brady Connection. AB - W. Horsley Gantt and Joseph V. Brady laid a rich foundation for understanding the concept of emotion, derived from 2 prominent traditions of physiology and psychology: classic conditioning and operant conditioning, respectively. This framework guided my fierce interest in motivation in general and the interaction between reward and stress, which began at John Hopkins with my thesis work under the guidance of Drs. Zoltan Annau, Solomon Synder, and Joseph Brady, among many others. Using the study of the neurobiology of addiction as a framework, I argue that drug addiction not only involves positive reinforcement associated with the rewarding effects of drugs of abuse but also involves another major source of reinforcement, specifically negative reinforcement driven by negative emotional states (termed the "dark side" of addiction). Excessive activation of the brain reward systems leads to antireward or a decrease in the function of normal reward related neurocircuitry and persistent recruitment of the brain stress systems, both of which may be neurobiologically linked. Understanding the neuroplasticity of the neurocircuitry that comprises the negative reinforcement associated with addiction is a key to understanding negative emotional states in general and their pathophysiology. PMID- 27356123 TI - Neuroticism and Negative Urgency in Problematic Alcohol Use: A Pilot Study. AB - BACKGROUND: Problematic alcohol use is common among university students and personality might account for individual differences in developing this maladaptive behavior. Two personality dispositions implicated in problematic alcohol use are negative urgency and neuroticism. However, the relationship of these traits to problematic alcohol use is unclear. In college students high neuroticism is not directly linked to problematic alcohol use. On the other hand, the experience of emotional distress in people high in neuroticism could impair the capacity for impulse control. Loss of impulse control under conditions of negative affect could trigger impulsive drinking and problematic alcohol use in the long run. OBJECTIVES: We investigated this idea by testing whether negative urgency mediates the relationship of neuroticism to problematic alcohol use. METHODS: Participants were 60 undergraduate university students who completed the Urgency subscale of the Urgency, (lack of) Premeditation, (lack of) Perseverance, Sensation Seeking, and Positive Urgency Impulsive Behaviour scale (UPPS-P), the Alcohol Use Disorders Identification Test (AUDIT), and the Neuroticism subscale of the Eysenck Personality Questionnaire Revised short form (EPQ-RSS). RESULTS: The results confirmed our hypothesis as we found an indirect effect of negative urgency on the relationship between neuroticism and problematic alcohol use. CONCLUSIONS/IMPORTANCE: It appears that it is not distress but the tendency to act rashly when distressed that is important in developing problematic alcohol drinking in university students. PMID- 27356122 TI - Risk factors for metachronous colorectal cancer or polyp: A systematic review and meta-analysis. AB - BACKGROUND AND AIM: We conducted a systematic review and meta-analysis to identify personal, lifestyle, and tumor-related risk factors for metachronous colorectal cancer (CRC) and polyp. METHODS: Relevant studies were identified by searching MEDLINE, Web of Science and Cochrane Central Register through 15 May 2016. Estimates for associations were summarized using random effects models. RESULTS: Fifty-five studies were included in the review. For individuals who had a CRC resection, having a synchronous polyp was a risk factor for metachronous CRC or polyp (relative risk [RR], 2.04; 95% confidence interval [CI], 1.48-2.82) and having a synchronous CRC (RR, 1.90; 95% CI, 1.25-2.91) and proximally located CRC (RR, 2.12; 95% CI, 1.24-3.64) were risk factors for metachronous CRC. For individuals who had a polypectomy, larger size (RR, 4.26; 95% CI, 2.11-8.57) or severe dysplasia of the initial polyp (RR, 5.15; 95% CI, 2.02-13.14), and having a synchronous polyp (RR, 2.52; 95% CI, 1.35-4.73) were risk factors for metachronous CRC; and a family history of CRC (RR, 1.90; 95% CI, 1.26-2.87), having a synchronous polyp (RR, 2.47; 95% CI, 1.74-3.50) and a larger size (RR, 1.49; 95% CI, 1.03-2.15) and proximal location of the initial polyp (RR, 1.20; 95% CI, 1.02-1.40) were risk factors for metachronous polyp. Meta-regression showed duration of follow-up was not a source of heterogeneity for most associations. There was no evidence that lifestyle factors were associated with metachronous CRC or polyp risk. CONCLUSION: A comprehensive list of risk factors identified for metachronous CRC or polyp may have important clinical implications. PMID- 27356124 TI - Myostatin and carbohydrate disturbances. AB - : Purpose/aim of the study: Myostatin is a myokine that has been shown to inhibit muscle growth and to have potentially deleterious effects on metabolism. The aim of the current study was to compare its circulating serum levels in subjects from the whole spectrum of carbohydrate disturbances leading to diabetes. MATERIALS AND METHODS: A total of 159 age-, sex-, and BMI-matched subjects participated in the study - 50 had normal glucose tolerance (NGT), 60 had prediabetes (PreDM), and 49 had type 2 diabetes mellitus (T2D). Oral glucose tolerance testing was used to determine glucose tolerance. Serum myostatin was quantified by means of ELISA. RESULTS: Circulating serum myostatin levels were highest in patients with T2D, lower in subjects with prediabetes, and lowest in subjects with normoglycemia (all p < 0.05). Myostatin was shown to be positively associated with fasting plasma glucose, HOMA-IR, hepatic enzymes, uric acid, and FINDRISC questionnaire scores in both sexes. ROC analyses determined circulating myostatin levels to be of value for differentiating subjects with T2D (AUC = 0.72, p = 0.002 in men; AUC = 0.70, p = 0.004 in women) in the study population. After adjustment for potential confounders, in a multiple binary logistic regression model, serum myostatin added further information to traditional risk estimates in distinguishing subjects with T2D. CONCLUSIONS: Serum myostatin levels are higher with deterioration of carbohydrate tolerance. Furthermore, circulating myostatin is positively associated with traditional biochemical estimates of poor metabolic health. These data add to evidence of the involvement of this myokine in the pathogenesis of T2D. PMID- 27356125 TI - Endoscopic suturing for the prevention of stent migration in benign upper gastrointestinal conditions: a comparative multicenter study. AB - BACKGROUND AND STUDY AIMS: Fully covered self-expandable metal stents (FCSEMSs) have increasingly been used in benign upper gastrointestinal (UGI) conditions; however, stent migration remains a major limitation. Endoscopic suture fixation (ESF) may prevent stent migration. The aims of this study were to compare the frequency of stent migration in patients who received endoscopic suturing for stent fixation (ESF group) compared with those who did not (NSF group) and to assess the impact of ESF on clinical outcome. PATIENTS AND METHODS: This was a retrospective study of patients who underwent FCSEMS placement for benign UGI diseases. Patients were divided into either the NSF or ESF group. Outcome variables, including stent migration, clinical success (resolution of underlying pathology), and adverse events, were compared. RESULTS: A total of 125 patients (44 in ESF group, 81 in NSF group; 56 benign strictures, 69 leaks/fistulas/perforations) underwent 224 stenting procedures. Stent migration was significantly more common in the NSF group (33 % vs. 16 %; P = 0.03). Time to stent migration was longer in the ESF group (P = 0.02). ESF appeared to protect against stent migration in patients with a history of stent migration (adjusted odds ratio [OR] 0.09; P = 0.002). ESF was also significantly associated with a higher rate of clinical success (60 % vs. 38 %; P = 0.03). Rates of adverse events were similar between the two groups. CONCLUSIONS: Endoscopic suturing for stent fixation is safe and associated with a decreased migration rate, particularly in patients with a prior history of stent migration. It may also improve clinical response, likely because of the reduction in stent migration. PMID- 27356126 TI - Colonic mucosal N-methyl-D-aspartate receptor mediated visceral hypersensitivity in a mouse model of irritable bowel syndrome. AB - OBJECTIVE: The aim of this study was to investigate whether colonic mucosal N methyl-D-aspartate receptor (NMDAR) participates in visceral hypersensitivity in irritable bowel syndrome (IBS). METHODS: C57BL/6 mice were administered intrarectally with trinitrobenzenesulfonic acid (TNBS) for the establishment of an IBS-like visceral hypersensitivity model. Those received an equivalent volume of 50% ethanol were regarded as the controls. Abdominal withdrawal reflex (AWR) scores in response to colorectal distention (CRD) were used to assess visceral sensitivity. NMDAR levels in the colonic mucosa were detected by both immunohistochemistry and Western blot. The concentrations of glutamate and ammonia in the feces of the mice were measured. Changes in visceral sensitivity after the intracolonic administration of ammonia or NMDAR antagonist were recorded. RESULTS: The established IBS-like mouse model of visceral hypersensitivity showed no evident inflammation in the colon. NMDAR levels in the colonic mucosa of the IBS-like mice were significantly higher compared with the controls, and were positively associated with AWR scores. The glutamate level in the feces of the TNBS-treated mice was similar to that of the controls, although the ammonia level was significantly higher. Intracolonic administration of ammonia induced visceral hypersensitivity in mice, which was repressed by pretreatment with NMDAR antagonist MK801. CONCLUSIONS: Overexpressed NMDAR in the colonic mucosa may participate in the pathogenesis of visceral hypersensitivity in IBS. Our study identifies the effect of ammonia in the colonic lumen on NMDAR in the colonic mucosa as a potential novel targeted mechanism for IBS treatment. PMID- 27356143 TI - A Randomized, Controlled Trial to Assess the Effect of Topical Insulin Versus Normal Saline in Pressure Ulcer Healing. AB - Insulin has been used in wound healing to increase wound collagen, granulation tissue, wound tensile strength, and local production of insulin-like growth factors by fibroblasts. Saline is a widely used irrigating and wound dressing solution. Patients admitted to an acute care facility who had a Grade 2 or Grade 3 pressure ulcer were recruited to participate in a randomized, controlled trial to compare the effect of normal saline-impregnated gauze and insulin dressing in pressure ulcer healing. Persons with immunodeficiency, diabetes mellitus, pregnancy, osteomyelitis, and peripheral vascular illness were not eligible for the study. Study participants were randomized to receive either normal saline dressing gauze or insulin dressing twice daily for 7 days. At baseline, patient demographic data and ulcer history were recorded. Baseline and follow-up ulcer assessments (days 4 and day 7) included ulcer measurement (length and width) and completion of the Pressure Ulcer Scale for Healing (PUSH version 3.0) tool. Patients in the control group received dressings of sterile gauze soaked with normal saline; patients in the intervention group received topical insulin (1 U/cm2 wound area). The insulin was sprayed over the wound surface with an insulin syringe, allowed to dry for 15 minutes, and then covered with sterile gauze. To ascertain the safety of study participants, blood glucose levels were measured with a glucometer 10 minutes before and 1 hour after the topical insulin application in the intervention group. Treatment efficacy was deter- mined by assessing the reduction in wound area and PUSH scores at follow-up. Statistical analysis was performed; data are expressed as mean +/- SD and percentage for continuous and categorical variables respectively. The differences in PUSH score and ulcer sizes between the 2 groups were analyzed using independent t-test, and within-group differences were analyzed using ANOVA with repeated measures; Greenhouse-Geisser correction was applied for the 3 consecutive measurements (day 1, day 4 and day 7). Fifty (50) patients (40 men, 10 women), ages 42.46 +/- 15.47 years, with 50 ulcers, 25 in each treatment group, were enrolled. At baseline, demographic variables and wound characteristics were comparable between the 2 groups. By day 7, mean wound area had decreased from 11.79 +/- 8.97 cm2 (day 1) to 11.43 +/- 9.06 cm2 in the saline group (P = 0.566) and from 9.61 +/- 6.39 cm2 (day 1) to 6.24 +/- 4.33 cm2 (P less than 0.01) in the insulin group. Mean PUSH scores decreased from 10.52 +/- 2.37 at baseline to 10.36 +/- 2.40 on day 7 in the saline group (P = 0.475), and from 10.28 +/- 1.10 to 8.52 +/- 1.58 on day 7 (P less than 0.01) in the insulin group. No significant decrease in blood glucose level before and after insulin application (P greater than 0.05) was observed. Treatment with topical insulin was found be safe and effective in reducing pressure ulcer size as compared to normal saline-soaked gauze. Future studies utilizing larger sample sizes, longer follow-up times, and different types of chronic wounds and control treatments are warranted. PMID- 27356144 TI - Estimating the Clinical Outcomes and Cost Differences Between Standard Care With and Without Cadexomer Iodine in the Management of Chronic Venous Leg Ulcers Using a Markov Model. AB - Chronic venous leg ulcers (VLUs) affect up to 1% of the adult population in the developed world and present a significant financial and resource burden to health care systems. Cadexomer iodine (CI) is an antimicrobial dressing indicated for use in chronic exuding wounds. The aim of this study was to estimate the cost utility of using CI + standard care (SC) - ie, high compression multicomponent bandaging including debridement - compared with SC alone in the management of chronic (>6 months' duration) VLUs from a payer's perspective. A Markov model was constructed to evaluate the cost and clinical benefits (healing and decreased infection rates) of the 2 treatment modalities over a 1-year period using data from 4 randomized, controlled clinical studies (RCTs) included in a recent Cochrane review and cost data from a recently published economic evaluation of VLUs. Costs were calculated using 2014 United States dollars; wound outcomes in- cluded complete healing in 212 patients reported in the Cochrane meta-analysis and quality-adjusted life years (QALYs), with utility values obtained from 200 patients with VLUs calculated using standard gamble. Treatment with CI over 1 year was $7,259 compared to $7,901 for SC. This resulted in a cost savings of $643/patient in favor of CI compared with SC. More patients treated with CI (61%) had their wounds healed compared to 54% treated with SC. Furthermore, patients treated with CI+SC experienced 6 additional ulcer-free weeks compared to persons treated with SC alone (ie, 25 ulcer- free weeks compared to 19 ulcer-free weeks, respectively). Overall, CI resulted in 0.03 more QALYs (ie, 0.86 QALYs compared to 0.83 for SC). The use of CI in addition to SC compared to SC alone over 52 weeks resulted in more wounds healed and more QALYs along with a decrease of overall costs The results of this study suggest CI is cost effective com- pared to SC alone in the management of patients with chronic VLUs. Prospective, controlled clinical studies are needed to elucidate the effect and cost effectiveness of CI on VLUs with and without signs of infection as compared to SC, other antiseptics, and more advanced topical treatment modalities. PMID- 27356145 TI - Polymeric Membrane Dressings for Topical Wound Management of Patients With Infected Wounds in a Challenging Environment: A Protocol With 3 Case Examples. AB - Patients with acute wounds often delay seeking medical assistance until an incapacitating infection has developed. When such patients come for help at a remote Christian clinic in northern Ghana, West Africa, the goals of care are to resolve and prevent a return of infection, decrease pain, enable an immediate return to normal activities, and facilitate healing. Because the local protocol of care, Edinburgh University Solution of Lime (EUSOL)-soaked gauze, did not meet these goals, the author tried using a variety of donated wound dressing regimens. Ultimately, polymeric membrane dressings (PMDs) were observed to meet patient care needs while also reducing clinic staff time and resources, and a PMD protocol of care was developed. Three (3) representative patients who presented with acute wounds and infection are described: a 20-year-old man with a hand abscess, a 16-year-old boy with a malleolus wound, and an approximately 20-year old woman with an injection abscess, all otherwise relatively healthy, albeit undernourished. All 3 patients re- ceived oral antibiotics, their wounds were initially cleansed and debrided, and an appropriate configuration of either regular or silver-containing PMDs was applied to all exposed wound surfaces. Dressing changes were scheduled based upon the personalized plan of care. In all 3 patients, the pain-relieving properties of PMDs allowed resumption of activi- ties within 1 day of initiating treatment, the dressings' continuous wound cleansing system kept the wounds clean and free of infection despite the challenging environment, and the wounds healed steadily. Managing infected acute wounds with PMDs through complete wound closure was time efficient for clinic staff and met all 4 major patient goals of care. Randomized, controlled studies to compare wound and quality of life outcomes in patients whose infected wounds are managed with PMDs compared with those whose wounds are managed with other advanced dressings are warranted. PMID- 27356146 TI - Description of a Simple Method of Stoma Protection During Prone Positioning. AB - Surgeries conducted with the patient in the prone position are frequent and can be lengthy. Abdominal stomas and su- prapubic catheters require protection for the complete duration of the procedure to avoid complications such as stomal ischemia, bleeding, or mucocutaneous separation. Standard protection strategies such as pillows and wedges can eas- ily fail. In the course of managing several patients who had sustained ostomy complications following surgery in a prone position, a simple method of stoma protection was devised. Instead of discarding the foam headrest typically used dur- ing induction by anesthesia staff, this device is placed with its central recess over the stoma and secured to the patient's abdominal wall with gentle tape just before turning the patient into a prone position. This method, used in more than 80 patients, has been found to effectively relieve pressure, and no complications have been observed. The foam shape also enables unobstructed drainage of fluids, facilitating collection and preventing leakage and contamination of the surgical field. Because the device is widely used by anesthesia, it is readily available and does not add any extra cost. PMID- 27356147 TI - Predictors for the occurrence of major complications after primary Roux-en-Y gastric bypass surgery. AB - BACKGROUND: The risk of developing postoperative complications after primary Roux en-Y gastric bypass (RYGB) is relatively low. Nevertheless, postoperative complications can have serious consequences in terms of severe morbidity and health care costs. Identification of potential predictors is useful for further reduction of the postoperative complication rate. METHODS: This retrospective study included all patients undergoing primary RYGB between January 2010 and December 2013, using data from a prospectively collected database. Patients' characteristics, operative details and perioperative outcome were analyzed. RESULTS: A total of 773 patients (14.5% male) were included for analysis, with a mean age of 42.1+/-10.4 years and a mean Body Mass Index of 42.8+/-4.3 kg/m2. A total of 66 (8.5%) direct postoperative complications occurred. Clavien-Dindo grade 3a and higher occurred in 55 patients. Univariate analysis identified age (P=0.013), gender (P=0.017), BMI over 50 kg/m2 (P=0.096), hypertension (P=0.099), chronic obstructive pulmonary disease (P=0.002) and previous upper gastrointestinal surgery (P=0.095) as potential predictors. Multivariate logistic regression analysis showed that male gender (OR 2.412; 95%CI [1.212-4.797]) and chronic obstructive pulmonary disease (COPD) (OR 3.716; 95%CI [1.543-8.949]) were found to be independent predictors for the occurrence of major complications after primary RYGB. CONCLUSIONS: This study showed a number of potential predictors, of which male gender and COPD after multivariate regression analysis were found to be independent predictive factors for the occurrence of major complications after primary RYGB. PMID- 27356148 TI - Pancreas preserving surgery for duodenal gastrointestinal stromal tumor removal. AB - BACKGROUND: We reported our experience with high-risk, non-metastatic second portion duodenal gastrointestinal stromal tumor (GIST)s in patients who underwent 1-month neoadjuvant cycles with imatinib therapy followed by pancreas-preserving surgery and 12-month of adjuvant chemotherapic regimen including imatinib. This study was conducted to evaluate the short and long-term results. METHODS: The study was conducted between January 2010 and May 2015. Medical charts and operative logbooks of patients were retrospectively reviewed. RESULTS: Nine patients form the basis of the current analysis. All patients underwent curative resection with pancreas preservation, and all specimens had histologically negative margins. The median follow-up was 35 months. Eight patients were alive, 1 patient died for myocardial infarction at a mean follow-up of 10 months, 1 patient had a recurrence at a mean follow-up of 32 months and no patients developed distant metastases. CONCLUSIONS: We are confident to suggest the use of neoadjuvant and adjuvant Imatinib therapy to those patients affected with D2, high-risk, duodenal GISTs to allow a limited resection. PMID- 27356150 TI - Physical and mechanical properties of PLA, and their functions in widespread applications - A comprehensive review. AB - Poly(lactic acid) (PLA), so far, is the most extensively researched and utilized biodegradable aliphatic polyester in human history. Due to its merits, PLA is a leading biomaterial for numerous applications in medicine as well as in industry replacing conventional petrochemical-based polymers. The main purpose of this review is to elaborate the mechanical and physical properties that affect its stability, processability, degradation, PLA-other polymers immiscibility, aging and recyclability, and therefore its potential suitability to fulfill specific application requirements. This review also summarizes variations in these properties during PLA processing (i.e. thermal degradation and recyclability), biodegradation, packaging and sterilization, and aging (i.e. weathering and hygrothermal). In addition, we discuss up-to-date strategies for PLA properties improvements including components and plasticizer blending, nucleation agent addition, and PLA modifications and nanoformulations. Incorporating better understanding of the role of these properties with available improvement strategies is the key for successful utilization of PLA and its copolymers/composites/blends to maximize their fit with worldwide application needs. PMID- 27356149 TI - Recent advances in self-assembled peptides: Implications for targeted drug delivery and vaccine engineering. AB - Self-assembled peptides have shown outstanding characteristics for vaccine delivery and drug targeting. Peptide molecules can be rationally designed to self assemble into specific nanoarchitectures in response to changes in their assembly environment including: pH, temperature, ionic strength, and interactions between host (drug) and guest molecules. The resulting supramolecular nanostructures include nanovesicles, nanofibers, nanotubes, nanoribbons, and hydrogels and have a diverse range of mechanical and physicochemical properties. These molecules can be designed for cell-specific targeting by including adhesion ligands, receptor recognition ligands, or peptide-based antigens in their design, often in a multivalent display. Depending on their design, self-assembled peptide nanostructures have advantages in biocompatibility, stability against enzymatic degradation, encapsulation of hydrophobic drugs, sustained drug release, shear thinning viscoelastic properties, and/or adjuvanting properties. These molecules can also act as intracellular transporters and respond to changes in the physiological environment. Furthermore, this class of materials has shown sequence- and structure-dependent impacts on the immune system that can be tailored to non-immunogenic for drug targeting, and immunogenic for vaccine delivery. This review explores self-assembled peptide nanostructures (beta sheets, alpha helices, peptide amphiphiles, amino acid pairing, elastin like polypeptides, cyclic peptides, short peptides, Fmoc peptides, and peptide hydrogels) and their application in vaccine delivery and drug targeting. PMID- 27356151 TI - Cavity partition and functionalization of a [2+3] organic molecular cage by inserting polar P[double bond, length as m-dash]O bonds. AB - The cavity of a [2+3] organic molecular cage was partitioned and functionalized by inserting inner-directed P[double bond, length as m-dash]O bonds, which shows CO2 capture and CH4 exclusion due to the size-matching and polarity effects. Computational results demonstrate that the successful segmentation via polar P[double bond, length as m-dash]O bonds facilitates the CO2 molecules to reside selectively inside the cavity. PMID- 27356152 TI - Managing multiple chronic conditions in Singapore - Exploring the perspectives and experiences of family caregivers of patients with diabetes and end stage renal disease on haemodialysis. AB - OBJECTIVE: Diabetes mellitus (DM) is the commonest cause of end stage renal disease (ESRD). Despite increasing DM-ESRD prevalence and high dependency on care, there is a lack of literature on DM-ESRD caregivers. We sought to explore the perspectives and experiences of caregivers of patients with DM undergoing haemodialysis in Singapore. DESIGN: This study employed an exploratory, qualitative design comprising in-depth interviews with caregivers of DM-ESRD patients. METHODS: Semi-structured interviews were conducted with a sample of 20 family caregivers (54.2 +/- 12.6 years; 75% female) of DM-ESRD patients. Data were analysed using Thematic Analysis. RESULTS: Key caregiving challenges identified were managing diet, care recipients' emotions and mobility dependence. Patients' emotional reactions caused interpersonal conflicts and hindered treatment management. Difficulties in dietary management were linked to patients' erratic appetite, caregivers' lack/poor understanding of the dietary guidelines and caregivers' low perceived competence. Limited resources in terms of social support and finances were also noted. Physical and psychological well-being and employment were adversely affected by caregiving role. CONCLUSION: This study highlights distinctive aspects of the DM-ESRD caregiving experience, which impact on caregivers' health and challenge care. Disease management programmes should be expanded to support caregivers in dealing with multimorbidity. PMID- 27356154 TI - Chromodomain Ligand Optimization via Target-Class Directed Combinatorial Repurposing. AB - Efforts to develop strategies for small-molecule chemical probe discovery against the readers of the methyl-lysine (Kme) post-translational modification have been met with limited success. Targeted disruption of these protein-protein interactions via peptidomimetic inhibitor optimization is a promising alternative to small-molecule hit discovery; however, recognition of identical peptide motifs by multiple Kme reader proteins presents a unique challenge in the development of selective Kme reader chemical probes. These selectivity challenges are exemplified by the Polycomb repressive complex 1 (PRC1) chemical probe, UNC3866, which demonstrates submicromolar off-target affinity toward the non-PRC1 chromodomains CDYL2 and CDYL. Moreover, since peptidomimetics are challenging subjects for structure-activity relationship (SAR) studies, traditional optimization of UNC3866 would prove costly and time-consuming. Herein, we report a broadly applicable strategy for the affinity-based, target-class screening of chromodomains via the repurposing of UNC3866 in an efficient, combinatorial peptide library. A first-generation library yielded UNC4991, a UNC3866 analogue that exhibits a distinct selectivity profile while maintaining submicromolar affinity toward the CDYL chromodomains. Additionally, in vitro pull-down experiments from HeLa nuclear lysates further demonstrate the selectivity and utility of this compound for future elucidation of CDYL protein function. PMID- 27356157 TI - Biomimetic Transmembrane Channels with High Stability and Transporting Efficiency from Helically Folded Macromolecules. AB - Membrane channels span the cellular lipid bilayers to transport ions and molecules into cells with sophisticated properties including high efficiency and selectivity. It is of particular biological importance in developing biomimetic transmembrane channels with unique functions by means of chemically synthetic strategies. An artificial unimolecular transmembrane channel using pore containing helical macromolecules is reported. The self-folding, shape persistent, pore-containing helical macromolecules are able to span the lipid bilayer, and thus result in extraordinary channel stability and high transporting efficiency for protons and cations. The lifetime of this artificial unimolecular channel in the lipid bilayer membrane is impressively long, rivaling those of natural protein channels. Natural channel mimics designed by helically folded polymeric scaffolds will display robust and versatile transport-related properties at single-molecule level. PMID- 27356156 TI - Current Status of Cardiovascular Disease-Related Smartphone Apps Downloadable in China. AB - BACKGROUND: Smartphone apps present a great opportunity for the management of cardiovascular disease (CVD) as the adoption of apps becomes increasingly popular in China. Yet, little is known about the status of CVD-related Smartphone apps in the country. The aim of this study was to examine the current status of CVD related smartphone apps available for download in China. MATERIALS AND METHODS: Using CVD-related keywords written either in Chinese or English, the top 6 most popular smartphone app online stores in China were searched in September 2015. The information accountability of the selected apps was assessed with the Silberg scale. The key topic areas identified from the European Guidelines on cardiovascular disease prevention served to determine information coverage of the top 5 downloaded apps. RESULTS: The average Silberg score of 151 apps was 2.87 (out of 9) with most apps not revealing authors' qualifications and information references. There was also a lack of sponsorship disclosure and information update. Moreover, none of the top 5 downloaded apps covered all key areas of CVD management as recommended by the European Guidelines on cardiovascular disease prevention. There was little evidence of health professionals' involvement in the formation of the CVD-related apps. CONCLUSION: This study identified areas for improvement concerning information accountability and the scope of coverage of CVD-related apps downloadable in China. The findings may guide the future advancement of CVD-related apps and benefit CVD management in China. PMID- 27356155 TI - Outcomes of a Clinic-Based Educational Intervention for Cardiovascular Disease Prevention by Race, Ethnicity, and Urban/Rural Status. AB - BACKGROUND AND PURPOSE: Heart disease is the leading killer of women and remains poorly recognized in high-risk groups. We assessed baseline knowledge gaps and efficacy of a survey-based educational intervention. METHODS: Four hundred seventy-two women in clinical settings completed pre-/post-surveys for knowledge of: heart disease as the leading killer, risk factors (general and personal levels), heart attack/stroke symptoms, and taking appropriate emergency action. They received a clinic-based educational intervention delivered by healthcare professionals in the course of their clinical care. Change score analyses tested pre-/post-differences in knowledge after the educational intervention, comparing proportions by race, ethnicity, and urban/nonurban status. RESULTS: Knowledge and awareness was low in all groups, especially for American Indian women (p < 0.05). Awareness was overall highest for heart disease as the leading killer, but it was the lowest for taking appropriate action (13% of Hispanic, 13% of American Indian, 29% of African American, and 18% of nonurban women; p < 0.05). For all women, knowledge of the major risk factors was low (58%) as was knowledge of their personal levels for risk factors (73% awareness for hypertension, 54% for cholesterol, and 50% for diabetes). The intervention was effective (% knowledge gain) in all groups of women, particularly for raising awareness of: (1) heart disease as the leading killer in American Indian (25%), Hispanic (18%), and nonurban (15%) women; (2) taking appropriate action for American Indian (80%), African American (64%), non-Hispanic (55%), and urban (56%) women; (3) heart disease risk factors for Hispanic (56%) and American Indian (47%) women; and (4) heart disease and stroke symptoms in American Indian women (54% and 25%, respectively). CONCLUSIONS: Significant knowledge gaps persist for heart disease in high-risk women, suggesting that these gaps and groups should be targeted by educational programs. We specify areas of need, and we demonstrate efficacy of a clinic-based educational intervention that can be of utility to busy healthcare professionals. PMID- 27356158 TI - The ligand influence in stereoselective carbene transfer reactions promoted by chiral metal porphyrin catalysts. AB - The use of diazo reagents of the general formula N2C(R)(R1) as carbene sources to create new C-C bonds is of broad scientific interest due to the intrinsic sustainability of this class of reagents. In the presence of a suitable catalyst, diazo reagents react with several organic substrates with excellent stereo control and form N2 as the only by-product. In the present report the catalytic efficiency of metal porphyrins in promoting carbene transfer reactions is reviewed with emphasis on the active role of the porphyrin skeleton in stereoselectively driving the carbene moiety to the target substrate. The catalytic performances of different metal porphyrins are discussed and have been related to the structural features of the ligand with the final aim of rationalizing the strict correlation between the three-dimensional structure of the porphyrin ligand and the stereoselectivity of carbene transfer reactions. PMID- 27356160 TI - ORS: Call for Submissions. PMID- 27356159 TI - Distinctive Metabolism of Flavonoid between Cultivated and Semiwild Soybean Unveiled through Metabolomics Approach. AB - Soybeans are an important crop for agriculture and food, resulting in an increase in the range of its application. Recently, soybean leaves have been used not only for food products but also in the beauty industry. To provide useful and global metabolite information on the development of soy-based products, we investigated the metabolic evolution and cultivar-dependent metabolite variation in the leaves of cultivated (Glycine max) and semiwild (G. gracilis) soybean, through a (1)H NMR-based metabolomics approach, as they grew from V (vegetative) 1 to R (reproductive) 7 growth stages. The levels of primary metabolites, such as sucrose, amino acids, organic acids, and fatty acids, were decreased both in the G. gracilis and G. max leaves. However, the secondary metabolites, such as pinitol, rutin, and polyphenols, were increased while synthesis of glucose was elevated as the leaves grew. When metabolite variations between G. gracilis and G. max are compared, it was noteworthy that rutin and its precursor, quercetin-3 O-glucoside, were found only in G. gracilis but not in G. max. Furthermore, levels of pinitol, proline, beta-alanine, and acetic acid, a metabolite related to adaptation toward environmental stress, were different between the two soybean cultivars. These results highlight their distinct metabolism for adaptation to environmental conditions and their intrinsic metabolic phenotype. This study therefore provides important information on the cultivar-dependent metabolites of soybean leaves for better understanding of plant physiology toward the development of soy-based products. PMID- 27356161 TI - ORS Interview with Eric Soltycki. PMID- 27356162 TI - Scan MDCs for GPS-Based Gamma Radiation Surveys. AB - A method for estimating the minimum detectable concentration of a contaminant radionuclide in soil when scanning with gamma radiation detectors (known as the "scan MDC") is described in the Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM). This paper presents an alternate method for estimating scan MDCs for GPS-based gamma surveys based on detector efficiencies modeled with the probabilistic Monte Carlo N-Particle Extended (MCNPX) Transport simulation code. Results are compared to those provided in MARSSIM. An extensive database of MCNPX-based detection efficiencies has been developed to represent a variety of gamma survey applications and potential scanning configurations (detector size, scan height, size of contaminated soil volume, etc.), and an associated web-based user interface has been developed to provide survey designers and regulators with access to a reasonably wide range of calculated scan MDC values for survey planning purposes. PMID- 27356163 TI - Comparison of Various Spectra Methods Used in Vehicle-Based Nai(Tl) Spectrometry Survey. AB - Vehicle-based NaI(Tl) spectrometry is widely used in searching for lost sources. There are several spectra methods can be used to detect abnormal radiation caused by manmade nuclides among a sequence of spectra. In order to test which method has the highest sensitivity, an experiment was done, and three commonly used spectra methods were used to process the acquired spectra. The result indicated that: the noise adjusted singular value decomposition method is more sensitive than other methods. Finally, its drawback was also discussed. PMID- 27356164 TI - Programmatic Assessment of Potential Induced Radioactivity in Electron Beam Sterilization of Healthcare Products. AB - ISO 11137-1:2006 Sterilization of Healthcare Products-Radiation requires that the potential for induced radioactivity be evaluated for medical devices irradiated with electrons with energy more than 10 MeV. For a manufacturing operation where new devices are being developed, a practical program for making such an evaluation should be engrained in the process, including the device design phase, where selection of materials can make a difference in the potential for activation to occur as a result of the irradiation process. The program, which is based on general assumptions as to the likely activation processes and generalized process assessments is being implemented in three phases: (1) incorporating materials consideration in the design phase, (2) evaluating potential activation empirically, including measurement at the point of irradiation, and (3) implementing routine procedures for the program, including developing a data base of results for consideration in future design efforts. PMID- 27356165 TI - Key Performance Indicators in the Evaluation of the Quality of Radiation Safety Programs. AB - Beaumont is a multiple hospital health care system with a centralized radiation safety department. The health system operates under a broad scope Nuclear Regulatory Commission license but also maintains several other limited use NRC licenses in off-site facilities and clinics. The hospital-based program is expansive including diagnostic radiology and nuclear medicine (molecular imaging), interventional radiology, a comprehensive cardiovascular program, multiple forms of radiation therapy (low dose rate brachytherapy, high dose rate brachytherapy, external beam radiotherapy, and gamma knife), and the Research Institute (including basic bench top, human and animal). Each year, in the annual report, data is analyzed and then tracked and trended. While any summary report will, by nature, include items such as the number of pieces of equipment, inspections performed, staff monitored and educated and other similar parameters, not all include an objective review of the quality and effectiveness of the program. Through objective numerical data Beaumont adopted seven key performance indicators. The assertion made is that key performance indicators can be used to establish benchmarks for evaluation and comparison of the effectiveness and quality of radiation safety programs. Based on over a decade of data collection, and adoption of key performance indicators, this paper demonstrates one way to establish objective benchmarking for radiation safety programs in the health care environment. PMID- 27356166 TI - Changes in Occupational Radiation Exposures after Incorporation of a Real-time Dosimetry System in the Interventional Radiology Suite. AB - A statistical pilot study was retrospectively performed to analyze potential changes in occupational radiation exposures to Interventional Radiology (IR) staff at Lawrence General Hospital after implementation of the i2 Active Radiation Dosimetry System (Unfors RaySafe Inc, 6045 Cochran Road Cleveland, OH 44139-3302). In this study, the monthly OSL dosimetry records obtained during the eight-month period prior to i2 implementation were normalized to the number of procedures performed during each month and statistically compared to the normalized dosimetry records obtained for the 8-mo period after i2 implementation. The resulting statistics included calculation of the mean and standard deviation of the dose equivalences per procedure and included appropriate hypothesis tests to assess for statistically valid differences between the pre and post i2 study periods. Hypothesis testing was performed on three groups of staff present during an IR procedure: The first group included all members of the IR staff, the second group consisted of the IR radiologists, and the third group consisted of the IR technician staff. After implementing the i2 active dosimetry system, participating members of the Lawrence General IR staff had a reduction in the average dose equivalence per procedure of 43.1% +/- 16.7% (p = 0.04). Similarly, Lawrence General IR radiologists had a 65.8% +/- 33.6% (p=0.01) reduction while the technologists had a 45.0% +/- 14.4% (p=0.03) reduction. PMID- 27356168 TI - Core electron excitations in U(4+): modelling of the nd(10)5f(2)->nd(9)5f(3) transitions with n = 3, 4 and 5 by ligand field tools and density functional theory. AB - Ligand field density functional theory (LFDFT) calculations have been used to model the uranium M4,5, N4,5 and O4,5-edge X-ray absorption near edge structure (XANES) in UO2, characterized by the promotion of one electron from the core and the semi-core 3d, 4d and 5d orbitals of U(4+) to the valence 5f. The model describes the procedure to resolve non-empirically the multiplet energy levels originating from the two-open-shell system with d and f electrons and to calculate the oscillator strengths corresponding to the dipole allowed d(10)f(2) > d(9)f(3) transitions appropriate to represent the d electron excitation process. In the first step, the energy and UO2 unit-cell volume corresponding to the minimum structures are determined using the Hubbard model (DFT+U) approach. The model of the optical properties due to the uranium nd(10)5f(2)->nd(9)5f(3) transitions, with n = 3, 4 and 5, has been tackled by means of electronic structure calculations based on the ligand field concept emulating the Slater Condon integrals, the spin-orbit coupling constants and the parameters of the ligand field potential needed by the ligand field Hamiltonian from Density Functional Theory. A deep-rooted theoretical procedure using the LFDFT approach has been established for actinide-bearing systems that can be valuable to compute targeted results, such as spectroscopic details at the electronic scale. As a case study, uranium dioxide has been considered because it is a nuclear fuel material, and both atomic and electronic structure calculations are indispensable for a deeper understanding of irradiation driven microstructural changes occurring in this material. PMID- 27356167 TI - The fragile X mental retardation 1 gene (FMR1): historical perspective, phenotypes, mechanism, pathology, and epidemiology. AB - OBJECTIVES: To provide an historical perspective and overview of the phenotypes, mechanism, pathology, and epidemiology of the fragile X-associated tremor/ataxia syndrome (FXTAS) for neuropsychologists. METHODS: Selective review of the literature on FXTAS. RESULTS: FXTAS is an X-linked neurodegenerative disorder of late onset. One of several phenotypes associated with different mutations of the fragile X mental retardation 1 gene (FMR1), FXTAS involves progressive action tremor, gait ataxia, and impaired executive functioning, among other features. It affects carriers of the FMR1 premutation, which may expand when passed from a mother to her children, in which case it is likely to cause fragile X syndrome (FXS), the most common inherited developmental disability. CONCLUSION: This review briefly summarizes current knowledge of the mechanisms, epidemiology, and mode of transmission of FXTAS and FXS, as well as the neuropsychological, neurologic, neuropsychiatric, neuropathologic, and neuroradiologic phenotypes of FXTAS. Because it was only recently identified, FXTAS is not well known to most practitioners, and it remains largely misdiagnosed, despite the fact that its prevalence may be relatively high. PMID- 27356170 TI - Cardiac Protection in HER2-Targeted Treatment: How Should We Measure New Strategies? PMID- 27356169 TI - Alloying Behavior of Self-Assembled Noble Metal Nanoparticles. AB - The atomic redistribution processes occurring in multiparticle nanostructures are hardly understood. To obtain a more detailed insight, we applied high-resolution microscopic, diffraction and spectroscopic characterization techniques to investigate the fine structure and elemental distribution of various bimetallic aerogels with 1:1 compositions, prepared by self-assembly of single monometallic nanoparticles. The system Au-Ag exhibited a complete alloy formation, whereas Pt Pd aerogels formed a Pd-based network with embedded Pt particles. The assembly of Au and Pd nanoparticles resulted in a Pd-shell formation around the Au particles. This work confirms that bimetallic aerogels are subject to reorganization processes during their gel formation. PMID- 27356171 TI - High initial concentration versus low initial concentration sevoflurane for inhalational induction of anaesthesia. AB - BACKGROUND: Sevoflurane induction for general anaesthesia has been reported to be safe, reliable and well accepted by patients. Sevoflurane induction uses either low or high initial concentrations. The low initial concentration technique involves initially administering a low concentration of sevoflurane and gradually increasing the concentration of the dose until the patient is anaesthetized. The high initial concentration technique involves administering high concentrations from the beginning, then continuing with those high doses until the patient is anaesthetized. This review was originally published in 2013 and has been updated in 2016. OBJECTIVES: We aimed to compare induction times and complication rates between high and low initial concentration sevoflurane anaesthetic induction techniques in adults and children who received inhalational induction for general anaesthesia. We defined 'high' as greater than or equal to and 'low' as less than a 4% initial concentration. SEARCH METHODS: For the updated review, we searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE (1950 to February 2016), EMBASE (1980 to February 2016), Latin American Caribbean Health Sciences Literature (LILACS) (1982 to February 2016) and the Institute for Scientific Information (ISI) Web of Science (1946 to February 2016). We also searched the reference lists of relevant articles and conference proceedings and contacted the authors of included trials. The original search was run in September 2011. SELECTION CRITERIA: We sought all published and unpublished, randomized controlled trials comparing high versus low initial sevoflurane concentration inhalational induction. Our primary outcomes included two measures of anaesthesia (time to loss of the eyelash reflex (LOER) and time until a weighted object held in the patient's hand was dropped), time to successful insertion of a laryngeal mask airway (LMA) and time to endotracheal intubation. Other outcomes were complications of the technique. DATA COLLECTION AND ANALYSIS: We used standardized methods for conducting a systematic review as described in the Cochrane Handbook for Systematic Reviews of Interventions. Two review authors independently extracted details of trial methods and outcome data from reports of all trials considered eligible for inclusion. We conducted all analyses on an intention-to-treat basis, when possible. We estimated overall treatment effects by using a fixed-effect model when we found no substantial heterogeneity, whereas we applied the random-effects model in the presence of considerable heterogeneity. MAIN RESULTS: We reran the searches and included one new study (100 participants) in this updated review. In total, we included 11 studies with 829 participants, although most analyses were based on data from fewer participants and evidence of low quality. We noted substantial heterogeneity in the included trials. Thus, our results should be read with caution. It was not possible to combine trials for the primary outcome (LOER), but individual trials reported faster induction times (typically 24 to 82 seconds faster, 41 seconds (31.37 to 50.62)) with high initial concentration sevoflurane (six studies, 443 participants, low-quality evidence). Apnoea appeared to be more common in the high initial concentration sevoflurane group (risk ratio (RR) 3.14, 95% confidence interval (CI) 1.72 to 5.7, two studies, 160 participants, low quality evidence). We found no evidence of differences between the two groups in the incidence of cough (odds ratio (OR) 1.23, 95% CI 0.53 to 2.81, eight studies, 589 participants, low-quality evidence), laryngospasm (OR 1.59, 95% CI 0.16 to 15.9, seven studies, 588 participants, low-quality evidence), breath holding (OR 1.16, 95% CI 0.47 to 2.83, five studies, 389 participants, low-quality evidence), patient movement (RR 1.14, 95% CI 0.69 to 1.89, five studies, 445 participants, low-quality evidence) or bradycardia (OR 0.8, 95% CI 0.22 to 2.88, three studies, 199 participants, low-quality evidence), and the overall incidence of complications was low. AUTHORS' CONCLUSIONS: A high initial concentration sevoflurane technique probably offers more rapid induction of anaesthesia and a similar rate of complications, except for apnoea, which may be more common with a high initial concentration. However, this conclusion is not definitive because the included studies provided evidence of low quality. PMID- 27356172 TI - Comparison of Two Continuous Glucose Monitoring Systems, Dexcom G4 Platinum and Medtronic Paradigm Veo Enlite System, at Rest and During Exercise. AB - BACKGROUND: Despite technological advances, the accuracy of continuous glucose monitoring (CGM) systems may not always be satisfactory with rapidly changing glucose levels, as is notable during exercise. We compare the performance of two current and widely used CGM systems, Dexcom G4 Platinum (Dexcom) and Medtronic Paradigm Veo Enlite system (Enlite), during both rest and exercise in adults with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Paired sensor and plasma glucose (PG) values (total of 431 data pairs for Dexcom and 425 for Enlite) were collected from 17 adults (37.3 +/- 13.6 years) with T1D. To evaluate and compare the accuracy of sensor readings, criteria involving sensor bias (sensor minus PG levels), absolute relative difference (ARD), and percentage of readings meeting International Organization for Standardization (ISO) criteria were considered. RESULTS: Both Dexcom and Enlite performed equally well during the rest period, with respective mean/median biases of -0.12/-0.02 mmol/L versus -0.18/-0.40 (P = 0.78, P = 0.66) mmol/L and ARDs of 13.77/13.34% versus 12.38/11.95% (P = 0.53, P = 0.70). During exercise, sensor bias means/medians were -0.40/-0.21 mmol versus 0.26/-0.24 mmol/L (P = 0.67, P = 0.62) and ARDs were 22.53/15.13% versus 20.44/14.11% (P = 0.58, P = 0.68) for Dexcom and Enlite, respectively. Both sensors demonstrated significantly lower performance during exercise; median ARD comparison at rest versus exercise for both Dexcom and Enlite showed a P = 0.02. More data pairs met the ISO criteria for Dexcom and Enlite at rest, 73.6% and 76.9% compared with exercise 48.2% and 53.9%. CONCLUSION: Dexcom and Enlite demonstrated comparable overall performances during rest and physical activity. However, a lower accuracy was observed during exercise for both sensors, necessitating a fine-tuning of their performance with physical activity. PMID- 27356173 TI - Metal-Free C-H Alkyliminylation and Acylation of Alkenes with Secondary Amides. AB - Carbon-carbon bond formation by metal-free cross-coupling of two reactants with low reactivity represents a challenge in organic synthesis. Secondary amides and alkenes are two classes of bench-stable compounds. The low electrophilicity of the former and low nucleophilicity of the latter make the direct coupling of these two partners challenging yet highly desirable. We report herein an unprecedented intermolecular reaction of secondary amides with alkenes to afford alpha,beta-unsaturated ketimines or enones, which are versatile intermediates for organic synthesis and are prevalent in bioactive compounds and functional materials. Our strategy relies on the chemoselective activation of the secondary amide with trifluoromethanesulfonic anhydride (Tf2O)/2-fluoropyridine to generate a highly reactive nitrilium intermediate, which reacts efficiently with alkenes. This metal-free synthesis is characterized by its mild reaction conditions, excellent functional group tolerance and chemoselectivity, allowing the preparation of multi-functionalized compounds without using protecting groups. PMID- 27356174 TI - Effects of electromagnetic fields on osteoporosis: A systematic literature review. AB - Electromagnetic fields (EMFs) as a safe, effective and noninvasive treatment have been researched and used for many years in orthopedics, and the common use clinically is to promote fracture healing. The effects of EMFs on osteoporosis have not been well concerned. The balance between osteoblast and osteoclast activity as well as the balance between osteogenic differentiation and adipogenic differentiation of bone marrow mesenchymal stem cells plays an important role in the process of osteoporosis. A number of recent reports suggest that EMFs have a positive impact on the balances. In this review, we discuss the recent advances of EMFs in the treatment of osteoporosis from basic research to clinical study and introduce the possible mechanism. In addition, we presented future perspectives of application of EMFs for osteoporosis. PMID- 27356175 TI - Iodine-mediated construction of polyfunctionalized arylazopyrazoles from beta ketoesters or 2-arylpyrazol-3-ones and arylhydrazines. AB - This paper describes step-economic iodine-mediated construction of functionalized arylazopyrazoles in the presence of catalytic AgNO3 starting from simple beta ketoesters and two equivalents of arylhydrazines. This cascade reaction includes in situalpha-iodination of beta-ketoesters, pyrazol-3-one formation, substitution with a nitrogen nucleophile, and oxidation/aromatization. PMID- 27356176 TI - Tick front-of-pack label has a positive nutritional impact on foods sold in New Zealand. AB - OBJECTIVE: Nutritional impact of the Tick front-of-pack labelling programme was evaluated by investigating nutrient changes to the purchased food supply and the nutritional quality of Tick v. non-Tick products. Factors influencing manufacturers' decisions to develop and license Tick products were also explored. DESIGN: Observational, cross-sectional and change over time data. SETTING: New Zealand food supply, 2011-2013. SUBJECTS: Forty-five newly licensed Tick products from five food categories were analysed: Edible Oil Spreads, Yoghurt & Dairy Desserts, Frozen Desserts, Ready Meals and Processed Poultry. Four manufacturers of these products were interviewed. RESULTS: Eligible products (31 % of all Tick products in these categories) removed 4.1 million megajoules of energy, 156.0 tonnes of saturated fat, 15.4 tonnes of trans-fat and 4.0 tonnes of sodium from food products sold in New Zealand over three years. In each food category, these Tick products were, on average, 14-76 % lower in energy, saturated fat, trans-fat and sodium than non-Tick products, indicating healthier options. Participating manufacturers reported that international market trends and consumer demand for tasty, healthy foods primarily influenced Tick product development and sales. Tick was used as part of their marketing strategy as it was perceived as a credible, well-recognised logo for New Zealand consumers. Tick was cited as the primary initiative encouraging saturated fat reduction. CONCLUSIONS: The Tick Programme is continuing to encourage manufacturers to make meaningful improvements to the nutritional quality of the New Zealand food supply. Over time, these changes are likely to influence population nutrient intakes and reduce CVD risk factors. PMID- 27356177 TI - Thermally-induced single-crystal-to-single-crystal transformations from a 2D two fold interpenetrating square lattice layer to a 3D four-fold interpenetrating diamond framework and its application in dye-sensitized solar cells. AB - In this work, a rare 2D -> 3D single-crystal-to-single-crystal transformation (SCSC) is observed in metal-organic coordination complexes, which is triggered by thermal treatment. The 2D two-fold interpenetrating square lattice layer [Cd(IBA)2]n (1) is irreversibly converted into a 3D four-fold interpenetrating diamond framework {[Cd(IBA)2(H2O)].2.5H2O}n (2) (HIBA = 4-(1H-imidazol-1 yl)benzoic acid). Consideration is given to these two complexes with different interpenetrating structures and dimensionality, and their influence on photovoltaic properties are studied. Encouraged by the UV-visible absorption and HOMO-LUMO energy states matched for sensitizing TiO2, the two complexes are employed in combination with N719 in dye-sensitized solar cells (DSSCs) to compensate absorption in the ultraviolet and blue-violet region, offset competitive visible light absorption of I3(-) and reducing charge the recombination of injected electrons. After co-sensitization with 1 and 2, the device co-sensitized by 1/N719 and 2/N719 to yield overall efficiencies of 7.82% and 8.39%, which are 19.94% and 28.68% higher than that of the device sensitized only by N719 (6.52%). Consequently, high dimensional interpenetrating complexes could serve as excellent co-sensitizers and have application in DSSCs. PMID- 27356178 TI - Fabrication of Chiral-Selective Nanotubular Heterojunctions through Living Supramolecular Polymerization. AB - Novel, chiral-selective linear nanotubular heterojunctions were achieved by living supramolecular polymerization of perylenediimide (PDI) derivatives. We demonstrate that the chiral seed can effectively bias achiral PDI molecules to polymerize on its ends in the identical helical sense. More interestingly, the chiral seed can bias the opposite enantiomers to grow expitaxially from its ends even in excess amounts relative to the seed. Furthermore, we demonstrate that the biasing effect of the chiral seed on the opposite enantiomer is not dependent on the length of the chiral seed but is related to the intrinsic length of the elongated nanotube from the opposite enantiomer. The fabrication of chiral selective nanotubes was achieved by application of the unique biasing effect of the chiral seed in living supramolecular self-assembly. PMID- 27356179 TI - Characteristic Work Function Variations of Graphene Line Defects. AB - Line defects, including grain boundaries and wrinkles, are commonly seen in graphene grown by chemical vapor deposition. These one-dimensional defects are believed to alter the electrical and mechanical properties of graphene. Unfortunately, it is very tedious to directly distinguish grain boundaries from wrinkles due to their similar morphologies. In this report, high-resolution Kelvin potential force microscopy (KPFM) is employed to measure the work function distribution of graphene line defects. The characteristic work function variations of grain boundaries, standing-collapsed wrinkles, and folded wrinkles could be clearly identified. Classical and quantum molecular dynamics simulations reveal that the unique work function distribution of each type of line defects is originated from the doping effect induced by the SiO2 substrate. Our results suggest that KPFM can be an easy-to-use and accurate method to detect graphene line defects, and also propose the possibility to tune the graphene work function by defect engineering. PMID- 27356180 TI - Intercalation-Based Single-Molecule Fluorescence Assay To Study DNA Supercoil Dynamics. AB - DNA supercoiling crucially affects cellular processes such as DNA replication, gene expression, and chromatin organization. However, mechanistic understanding of DNA supercoiling and the related DNA-processing enzymes has remained limited, mainly due to the lack of convenient experimental tools to probe these phenomena. Here, we report a novel high-throughput single-molecule assay for real-time visualization of supercoiled DNA molecules, named ISD (Intercalation-induced Supercoiling of DNA). We use an intercalating dye to induce supercoiling of surface-attached DNA molecules as well as to visualize coiled-loop structures (i.e., plectonemes) formed on DNA. The technique is solely based on epifluorescence microscopy and requires no mechanical manipulation of the DNA molecules. This new assay allows to track positions and sizes of individual plectonemes and characterize their position-dependent dynamics such as nucleation, termination, and diffusion. We describe the ISD technique and demonstrate its potential by establishing that plectonemes are pinned to a local 10-nucleotide long mispaired sequence along a double-stranded DNA molecule. PMID- 27356181 TI - Maternal plasma n-3 and n-6 polyunsaturated fatty acid concentrations during pregnancy and subcutaneous fat mass in infancy. AB - OBJECTIVE: The associations of maternal plasma n-3 and n-6 polyunsaturated fatty acid (PUFA) concentrations during pregnancy with infant subcutaneous fat were examined. METHODS: In a population-based prospective cohort study among 904 mothers and their infants, maternal plasma n-3 and n-6 PUFA concentrations were measured at midpregnancy. Body mass index, total subcutaneous fat, and central-to total subcutaneous fat ratio were calculated at 1.5, 6, and 24 months. RESULTS: Maternal n-3 PUFA levels were not consistently associated with infant body mass index or total subcutaneous fat. Higher maternal total n-3 PUFA levels, and specifically eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid, were associated with higher central-to-total subcutaneous fat ratio at 1.5 months, whereas higher maternal total n-3 PUFA levels were associated with lower central-to-total subcutaneous fat ratio at 6 months (all P values < 0.05). These associations were not present at 24 months. Maternal n-6 PUFA levels were not consistently associated with infant subcutaneous fat. A higher n-6/n-3 ratio was associated with lower central-to-total subcutaneous fat ratio at 1.5 months only (P value < 0.05). CONCLUSIONS: Maternal n-3 PUFA levels during pregnancy may have transient effects on infant subcutaneous fat. Further studies are needed to assess the effects of maternal PUFA concentrations on fat mass development during early infancy. PMID- 27356182 TI - Small cell undifferentiated (SCUD) hepatoblastomas: All malignant rhabdoid tumors? AB - Small cell undifferentiated (SCUD) hepatoblastoma is a rare variant of hepatoblastoma with poor outcome and loss of INI1 expression, sharing this with malignant rhabdoid tumors (MRT). We studied all tumors from the files of the Kiel Pediatric Tumor Registry (KTR) with the initial diagnosis of SCUD and MRT. After re-review, we performed immunistochemistry, fluorescence in situ hybridization, and multiplex ligation dependent probe amplification for loss of expression and deletion of INI1/SMARCB1 in 23 tumors. Morphologically, 12 of the tumors had a small cell morphology, 9 showed the typical picture of MRT, and 2 were composed of both small cells and rhabdoid cells. All but 1 of the 23 tumors showed loss of INI1 protein expression by immunohistochemistry. Nineteen of the INI1 negative tumors were analyzed by FISH technique and all showed a deletion of the INI1/SMARCB1 gene (17 homozygous deletions, 2 heterozygous deletions). We investigated 14 of these cases by multiplex ligation dependent probe amplification and verified the deletions in all cases. In conclusion, we postulate that SCUD hepatoblastoma is not a hepatoblastoma but represents a malignant rhabdoid tumor of the liver. (c) 2016 Wiley Periodicals, Inc. PMID- 27356183 TI - Implementation of an Enzyme Linked Immunosorbent Assay for the Quantification of Allergenic Egg Residues in Red Wines Using Commercially Available Antibodies. AB - Since the early 2000s, labeling of potentially allergenic food components to protect people who suffer from food allergies is compulsory in numerous industrialized countries. In Europe, milk and egg components used during the winemaking process must be indicated on the label since July 1, 2012. Several ELISA procedures have been developed to detect allergenic residues in wines. However, the complexity of the wine matrix can inhibit the immunoenzymatic reaction. The aim of this study was to implement an ELISA assay for the detection of ovalbumin in red wines using commercially available antibodies. The specificity of the acquired antibodies and the absence of cross reactivity were assessed by immunoblotting and ELISA. An ELISA assay with a LOD of 14.2 MUg/L and a LOQ of 56.4 MUg/L of ovalbumin in aqueous solution was obtained. Differences in ELISA signals were observed when analyzing various fining agents, although reproducible conformation of the antigen could be reached for the comparison of ovalbumin and Ovicolle. The differences between samples in terms of pH could be leveled but the inhibition of the ELISA signal, positively correlated to the tannin content of the wines, could not be suppressed. Thus, standard curves of ovalbumin in several wines were obtained by relative quantification. The control steps and the difficulties encountered presented in this study should be considered by anybody working toward the development of ELISA assays for the detection of allergenic residues in complex food matrices. PMID- 27356185 TI - Corrole and Porphyrin Amino Acid Conjugates: Synthesis and Physicochemical Properties. AB - A series of conjugates of amino acids with porphyrins and corroles was synthesized. Their self-assembling ability under defined conditions was investigated by scanning electron microscopy. The morphology and photophysical properties of these molecules were studied by absorption and fluorescence spectroscopy in solid, liquid, and self-assembled forms. We observed that both corrole and porphyrin conjugated with the l-phenylalanine-l-phenylalanine peptide to form spherical nanostructures with bathochromic shifts in the emission spectra, indicating the formation of aggregates. These aggregates are characterized by the impressive absorption of light over nearly the whole visible range. The broadening of all bands was particularly strong in the case of corroles. The fluorescence lifetimes of self-assembled species were longer as compared to the solid-state form. PMID- 27356186 TI - Galectin-3-Binding Glycomimetics that Strongly Reduce Bleomycin-Induced Lung Fibrosis and Modulate Intracellular Glycan Recognition. AB - Discovery of glycan-competitive galectin-3-binding compounds that attenuate lung fibrosis in a murine model and that block intracellular galectin-3 accumulation at damaged vesicles, hence revealing galectin-3-glycan interactions involved in fibrosis progression and in intracellular galectin-3 activities, is reported. 3,3'-Bis-(4-aryltriazol-1-yl)thiodigalactosides were synthesized and evaluated as antagonists of galectin-1, -2, -3, and -4 N-terminal, -4 C-terminal, -7 and -8 N terminal, -9 N-terminal, and -9 C-terminal domains. Compounds displaying low nanomolar affinities for galectins-1 and -3 were identified in a competitive fluorescence anisotropy assay. X-ray structural analysis of selected compounds in complex with galectin-3, together with galectin-3 mutant binding experiments, revealed that both the aryltriazolyl moieties and fluoro substituents on the compounds are involved in key interactions responsible for exceptional affinities towards galectin-3. The most potent galectin-3 antagonist was demonstrated to act in an assay monitoring galectin-3 accumulation upon amitriptyline-induced vesicle damage, visualizing a biochemically/medically relevant intracellular lectin carbohydrate binding event and that it can be blocked by a small molecule. The same antagonist administered intratracheally attenuated bleomycin-induced pulmonary fibrosis in a mouse model with a dose/response profile comparing favorably with that of oral administration of the marketed antifibrotic compound pirfenidone. PMID- 27356188 TI - The cost-effectiveness of exenatide twice daily (BID) vs insulin lispro three times daily (TID) as add-on therapy to titrated insulin glargine in patients with type 2 diabetes. AB - OBJECTIVE: To evaluate the cost-effectiveness of exenatide twice daily (BID) vs bolus insulin lispro three times daily (TID) as add-on therapy when glycemic control is sub-optimal with titrated basal insulin glargine and metformin. METHODS: The analysis was based on the recent 4B Study, which compared exenatide BID and lispro TID as add-on therapies in subjects with type 2 diabetes insufficiently controlled, despite titrated insulin glargine. The Cardiff Diabetes Model was used to simulate patient costs and health benefits beyond the 4B Study. The Swedish healthcare perspective was adopted for this analysis; costs are reported in ?EUR to aid interpretation. The main outcome measure was the cost per quality-adjusted life-year (QALY) gained with exenatide BID compared to lispro TID. RESULTS: Exenatide BID was associated with an incremental cost of ?1,270 and a QALY increase of +0.64 compared with lispro TID over 40 years. The cost per QALY gained with exenatide BID compared with lispro TID was ?1,971, which is within conventional limits of cost-effectiveness. Cost-effectiveness results were generally robust to alternative assumptions and values for key model parameters. LIMITATIONS: Extrapolation of trial data over the longer term can be influenced by modeling and parameter uncertainty. Cost-effectiveness results were generally insensitive to alternative values of key model input parameters and across scenarios. CONCLUSIONS: The addition of exenatide BID rather than insulin lispro to basal insulin is associated with similar or better clinical outcomes. Illustrated from the Swedish healthcare perspective, analysis with the Cardiff Diabetes Model demonstrated that exenatide BID represents a cost-effective treatment alternative to lispro TID as add-on therapy in type 2 diabetes patients insufficiently controlled on basal insulin. PMID- 27356187 TI - Activation of gene transcription via CIM0216, a synthetic ligand of transient receptor potential melastatin-3 (TRPM3) channels. AB - Several compounds have been proposed to stimulate TRPM3 Ca2+ channels. We recently showed that stimulation of TRPM3 channels with pregnenolone sulfate activated the transcription factor AP-1, while other proposed TRPM3 ligands (nifedipine, D-erythro-sphingosine) exhibited either no or TRPM3-independent effects on gene transcription. Here, we have analyzed the transcriptional activity of CIM0216, a synthetic TRPM3 ligand proposed to have a higher potency and affinity for TRPM3 than pregnenolone sulfate. The results show that CIM0216 treatment of HEK293 cells expressing TRPM3 channels activated AP-1 and stimulated the transcriptional activation potential of c-Jun and c-Fos, 2 basic region leucine zipper transcription factors that constitute AP-1. CIM0216-induced gene transcription was attenuated by knock-down of TRPM3 or treatment with mefenamic acid, a TRPM3 inhibitor. CIM0216 was similarly or less capable in activating TRPM3-mediated gene transcription, suggesting that pregnenolone sulfate is still the ligand of choice for changing the gene expression pattern via TRPM3. PMID- 27356189 TI - Swallowing endoscopy findings in Huntington's disease: a case report. AB - Huntington's disease (HD) is a degenerative genetic disorder with autosomal dominant transmission. The triad of symptoms of this disease consists of psychiatric disorders, jerky movements, and dementia. Oropharyngeal dysphagia, which is more evident with disease progression, is also present. Few studies have addressed the swallowing characteristics using objective analysis in this population. The purpose of this research was to describe the swallowing endoscopic findings of the pharyngeal phase in HD. This is a cross-sectional study addressing a clinical case which included two individuals of the same family, male, 32 and 63 years old, designated as individual A and individual B, with progression of the disease for five and 13 years, respectively. Consistent liquid, nectar, and puree were offered during the evaluation. There was presence of posterior oral spillage in liquid and nectar, small amount of pharyngeal residues, and no laryngeal penetration or aspiration in the individuals with HD in this study. PMID- 27356190 TI - Relationship between vocal symptoms, severity of voice disorders, and laryngeal diagnosis in patients with voice disorders. PMID- 27356191 TI - Theory of Mind (ToM) and language: stimulating metalinguistic skills in people with dementia. AB - PURPOSE: The purpose of this paper was to assess the use of the Metalinguistic Skills Stimulation Program in Theory of Mind (ToM) in people with dementia. METHODS: An experimental research design was developed. Forty-two subjects, 28 women and 14 men, aged 61 to 87 participated in the study. The three following groups were created: Experimental Group and Control Group - both composed of people with dementia, and Normal Group - consisting of people without dementia or any medical and psychological disorders that keep them from living a normal life. All subjects in the sample were evaluated using the MMSE30 Test and the MetAphAs Test. The stimulation program was used with the Experimental Group in 40-minute sessions held twice a week for five months. After the program, a second evaluation or retest was performed. The data obtained were compared statistically and qualitatively, individually and between the different groups. RESULTS: A clear effect of the treatment was observed: most of the patients improved their average scores in the performance of various tasks and on the MetAphAs Test. Significant differences were observed when comparing the Experimental Group with the Control Group. CONCLUSIONS: The evolution of each patient presents a multifactorial etiology, and it was influenced by different variables related to the patients and their psychosocial environment. The data encourage the development of further research with larger samples in order to achieve more conclusive results. PMID- 27356192 TI - Adsorption and transformation of ammonium ion in a loose-pore geothermal reservoir: Batch and column experiments. AB - Adsorption kinetics and transformation process of ammonium ion (NH4(+)) were investigated to advance the understanding of N cycle in a low-temperature loose pore geothermal reservoir. Firstly, batch experiments were performed in order to determine the sorption capacity and the kinetic mechanism of NH4(+) onto a loose pore geothermal reservoir matrix. Then column experiments were carried out at temperatures from 20 degrees C to 60 degrees C in order to determine the transport parameters and transformation mechanism of NH4(+) in the studied matrix. The results showed that the adsorption process of NH4(+) onto the porous media well followed the pseudo-second-order model. No obvious variation of hydrodynamic dispersion coefficient (D) and retardation factor (R) was observed at different transport distances at a Darcy's flux of 2.27cm/h, at which nitrification could be neglected. The simulated D obtained by the CDE model in CXTFIT2.1 increased with temperature while R decreased with temperature, indicating that the adsorption capacity of NH4(+) onto the matrix decreased with the increasing of temperature. When the Darcy's flux was decreased to 0.014cm/h, only a little part of NH4(+) could be transformed to nitrate, suggesting that low density of nitrifiers existed in the simulated loose-pore geothermal reservoir. Although nitrification rate increased with temperature in the range of 20 degrees C to 60 degrees C, it was extremely low and no accumulation of nitrite was observed under the simulated low-temperature geothermal conditions without addition of biomass and oxygen. PMID- 27356193 TI - Psoriasis and psoriatic arthritis overview. AB - Psoriasis and psoriatic arthritis (PsA) are chronic immune-mediated diseases that primarily affect the skin and joints, respectively; these diseases are also associated with high rates of cardiovascular and other comorbidities. Despite over 40 genes proven to be related to the disease, the exact causes of psoriasis and PsA are still to be determined. Recent insights into the underlying pathophysiology of these diseases have revealed novel therapeutic targets. Effective management requires timely diagnosis and initiation of treatment. Yet, both psoriasis and PsA remain underrecognized and undertreated in current clinical practice. Recognizing the true physical, social, and emotional burden of psoriasis and PsA, as well as their associated comorbidities, is the first step to improving the prognosis for affected patients. PMID- 27356194 TI - Psoriasis and psoriatic arthritis treatment. AB - Over the past several years, an increased understanding of the pathophysiology of psoriasis and psoriatic arthritis (PsA) has led to the development of several new biologic therapies. Appropriate treatment selection and timing may slow, and even halt, the progression of psoriasis and PsA; as a result, it can decrease the economic burden. As treatment options vary based on individual disease characteristics and patient preferences, reviewing the patient's complete clinical picture is imperative. An updated treatment algorithm, based on patients' most severe disease domain, is now available to guide the selection of optimal therapy. Special care should be given to patients with both psoriasis and PsA who experience multiple disease domains, a heavy symptom burden, and an increased risk of comorbidities. PMID- 27356195 TI - Managed care aspects of psoriasis and psoriatic arthritis. AB - The chronic and systemic nature of psoriasis has a significant impact on direct costs, indirect costs, and patient quality of life. Psoriasis is associated with comorbid conditions that add to the burden of the disease, especially in moderate to severe disease. The total estimated annual healthcare burden of psoriasis may be as high as $35.2 billion, with $12.2 billion in direct costs and $23 billion in indirect costs (attributed to reduced health-related quality of life and lost productivity). These costs vary based on the severity of the disease; pharmacy costs account for the majority of the burden, especially in severe disease. Biologic therapies are largely responsible for the pharmacy costs. Approval of biosimilar products in the near future may ease some of this burden for payers and patients, although new agents have also been recently approved, with more in the pipeline. The healthcare costs of psoriasis management substantially increase with comorbid conditions, such as heart disease, hyperlipidemia, hypertension, diabetes, and lung disease. These comorbidities also include psychiatric conditions, such as social stigmatization, depression, and suicide. The overall costs associated with comorbidities are estimated to be an additional $22,713 per patient per year. Appropriate treatment selection and timing may curtail the progression of psoriasis, and, as a result, can decrease the economic burden. As treatment options vary based on comorbidities, long-term remission goals, and medication costs, conducting a comprehensive patient assessment is imperative. Drug utilization reviews steered by specialty pharmacists may help reduce costs and improve outcomes by providing treatment monitoring and patient education. PMID- 27356196 TI - Identification of subpopulations with distinct treatment benefit rate using the Bayesian tree. AB - Characterization of a subpopulation by the difference in marginal means of the outcome under the intervention and control may not be sufficient to provide informative guidance for individual decision and public policy making. Specifically, often we are interested in the treatment benefit rate (TBR), that is, the probability of benefitting an intervention in a meaningful way. For binary outcomes, TBR is the proportion that has "unfavorable" outcome under the control and "favorable" outcome under the intervention. Identification of subpopulations with distinct TBR by baseline characteristics will have significant implications in clinical setting where a medical intervention with potential negative health impact is under consideration for a given patient. In addition, these subpopulations with unique TBR set the basis for guidance in implementing the intervention toward a more personalized scheme of treatment. In this article, we propose a Bayesian tree based latent variable model to seek subpopulations with distinct TBR. Our method offers a nonparametric Bayesian framework that accounts for the uncertainty in estimating potential outcomes and allows more exhaustive search of the partitions of the baseline covariates space. The method is evaluated through a simulation study and applied to a randomized clinical trial of implantable cardioverter defibrillators to reduce mortality. PMID- 27356197 TI - Osteomyelitis-Induced Sequester of Bovine-Derived Bone Mineral/Host Bone Composite 8 Years Post-Sinus Graft: A Case Report. AB - INTRODUCTION: Sinus grafts are a safe and predictable treatment for increasing bone volume in the posterior maxilla. Common complications include membrane perforations and postoperative infection. Little is published with regard to late onset infection except as it relates to periimplantitis. This report presents a case of late sequestration of bovine bone mineral graft fully consolidated within host lamellar bone, 8 years postsinus lift. Histology revealed mature lamellar bone encapsulating well-integrated particles of bovine bone material with evidence of devitalization and marrow spaces filled with a dense neutrophil infiltrate and a filamentous mixed microbial flora. RESULT: A histological diagnosis of osteomyelitis was given on analysis of the integrated bovine bone mineral sequester, 8 years after successful integration and functional loading. CONCLUSIONS: It can be concluded from this case report that there is a potential for breakdown and sequestration of bovine bone mineral/host bone composite grafts long after successful integration and consolidation. PMID- 27356198 TI - Fracture Resistance of Monolithic High Translucency Zirconia Implant-Supported Crowns. AB - AIM: To evaluate the resistance to axial forces of screw-retained monolithic high translucency zirconia (mHTZr) crowns compared with high translucency zirconia + feldspathic ceramic (HTZrC) crowns, low translucency zirconia + feldspathic ceramic (LTZrC) crowns, and metal-ceramic (MC) crowns, and also to observe the different fracture patterns between all groups. METHODS: Twenty-four crowns were fabricated (6 of each group) and loaded until failure, using a testing machine with a 5.0-kN load cell. RESULTS: Mean fracture results varied between 1092.7 N (LTZrC group) and 3439.7 N (mHTZr group). No statistically significant differences were found between the HTZrC, LTZrC, and MC groups. However, statistically significant differences (P < 0.05) were found between mHTZr and the other 3 groups. In the MC group, only chipping of the ceramic veneering occurred. In the mHTZr group, when fracturing occurred, it was of the whole structure. Finally, the LTZrC and HTZrC groups suffered both chipping and core fractures. CONCLUSION: High translucency monolithic zirconia implant-supported crowns proved to be the toughest group studied when an axial force was applied. Fracture patterns varied between different materials, chipping being the most common occurrence. PMID- 27356199 TI - A Flap Design for Alveolar Bone Augmentation: Inverted Double Flap. AB - PURPOSE: Although uneventful healing of soft tissue after primary closure of an augmented site represents the crucial point for bone regeneration in oral surgery, the reported incidence of wound dehiscence continues to remain at between 2.5% and 10%. The aim of this new flap design was to decrease complication incidence through double flap closure and stabile keratinized tissue volume. MATERIALS AND METHODS: Two patients who have partial edentulous alveolus with insufficient bone volume have been reached alveolus reconstruction with autogenous block graft. Before augmentation, flaps have been elevated with 2 layers as inverted double flap. RESULTS: Two patients healed without any complications. The keratinized tissue and vestibule depth were stable when compared with the preoperative positions. CONCLUSIONS: This article presents a new flap design that allows twice the coverage of the augmentation site when compared with other techniques and may thus help eliminate problems related to wound healing after augmentation. PMID- 27356200 TI - Effects of Food Texture on Three-Dimensional Loads on Implants During Mastication Based on In Vivo Measurements. AB - INTRODUCTION: The mechanisms by which the loads exerted on implants that support prostheses are modulated during mastication remain unclear. The purpose of this study was to evaluate the effects of food texture on 3-dimensional loads measured at a single implant using a piezoelectric transducer. MATERIALS AND METHODS: Two subjects participated in this study. The transducer and the experimental superstructure, which had been adjusted to the subject's occlusal scheme, were attached to the implant with a titanium screw. The foods tested were chewing gum and peanuts. RESULTS: The mean maximum load on the implant in each chewing cycle was significantly higher during peanut chewing than during gum chewing. The direction of maximum load was significantly more widely dispersed during peanut chewing than during gum chewing. The range of changes in load direction during the force-increasing phase of each chewing cycle was significantly wider during peanut chewing than during gum chewing. CONCLUSIONS: The load on the implant was affected by food texture in both subjects. This measurement method can be useful to investigate the mechanisms of load modulation on implants during mastication. PMID- 27356201 TI - Volumetric Evaluation of Safe Zone for Bone Harvesting From Symphysis Region by Using Cone Beam Computed Tomography. AB - OBJECTIVES: The aim of the present study was to retrospectively make a volumetric evaluation of symphysis sites of patients by the use of cone beam computed tomography (CBCT). METHODS: This retrospective study evaluated dentate symphysis region of the mandibles in CBCT scans taken for different reasons in 90 patients (45 women and 45 men). Three-dimensional (3D) data were obtained using a CBCT device Kodak 9000 3D CMOS sensor with optical fiber. CBCT images were then transferred as digital imaging and communications in medicine files and imported into a volumetric-rendering software 3D DOCTOR (Able Software Corp., Lexington, MA) capable of measurements of vector based-segmentation technology for volumetric measurements. RESULTS: The total average bone volume is 2616.45 mm. Significant differences in average bone volume were found between group I and group IV (P < 0.001). Higher bone volume was obtained in the male groups (2903.01 mm) than in the female groups (2329.88 mm). CONCLUSIONS: CBCT is a good candidate for 3D assessment of high-contrast structures in the oral region. We suggest that the use of 3D computed tomography in combination with a software program is a dependable means of measuring the volume of the symphysis bone graft. PMID- 27356202 TI - Removing energy from a beverage influences later food intake more than the same energy addition. AB - Designing reduced-calorie foods and beverages without compromising their satiating effect could benefit weight management, assuming that consumers do not compensate for the missing calories at other meals. Though research has demonstrated that compensation for overfeeding is relatively limited, the extent to which energy reductions trigger adjustments in later food intake is less clear. The current study tested satiety responses (characterised by changes in appetite and later food intake) to both a covert 200 kcal reduction and an addition of maltodextrin to a soymilk test beverage. Twenty-nine healthy male participants were recruited to consume three sensory-matched soymilk beverages across four non-consecutive study days: a medium energy control (ME: 300 kcal) and a lower energy (LE: 100 kcal) and higher energy (HE: 500 kcal) version. The ME control was consumed twice to assess individual consistency in responses to this beverage. Participants were unaware of the energy differences across the soymilks. Lunch intake 60 min later increased in response to the LE soymilk, but was unchanged after consuming the HE version. These adjustments accounted for 40% of the energy removed from the soymilk and 13% of the energy added in. Rated appetite was relatively unaffected by the soymilk energy content. No further adjustments were noted for the rest of the day. These data suggest that adult men tested were more sensitive to calorie dilution than calorie addition to a familiar beverage. PMID- 27356204 TI - Current Status of Prostate Cancer Diagnosis and Management in the United States. PMID- 27356203 TI - Glycemic increase induced by intravenous glucose infusion fails to affect hunger, appetite, or satiety following breakfast in healthy men. AB - Meal-dependent fluctuations of blood glucose and corresponding endocrine signals such as insulin are thought to provide important regulatory input for central nervous processing of hunger and satiety. Since food intake also triggers the release of numerous gastrointestinal signals, the specific contribution of changes in blood glucose to appetite regulation in humans has remained unclear. Here we tested the hypothesis that inducing glycemic fluctuations by intravenous glucose infusion is associated with concurrent changes in hunger, appetite, and satiety. In a single blind, counter-balanced crossover study 15 healthy young men participated in two experimental conditions on two separate days. 500 ml of a solution containing 50 g glucose or 0.9% saline, respectively, was intravenously infused over a 1-h period followed by a 1-h observation period. One hour before start of the respective infusion subjects had a light breakfast (284 kcal). Blood glucose and serum insulin concentrations as well as self-rated feelings of hunger, appetite, satiety, and fullness were assessed during the entire experiment. Glucose as compared to saline infusion markedly increased glucose and insulin concentrations (peak glucose level: 9.7 +/- 0.8 vs. 5.3 +/- 0.3 mmol/l; t(14) = -5.159, p < 0.001; peak insulin level: 370.4 +/- 66.5 vs. 109.6 +/- 21.5 pmol/l; t(14) = 4.563, p < 0.001) followed by a sharp decline in glycaemia to a nadir of 3.0 +/- 0.2 mmol/l (vs. 3.9 +/- 0.1 mmol/l at the corresponding time in the control condition; t(14) = -3.972, p = 0.001) after stopping the infusion. Despite this wide glycemic fluctuation in the glucose infusion condition subjective feelings of hunger, appetite satiety, and fullness did not differ from the control condition throughout the experiment. These findings clearly speak against the notion that fluctuations in glycemia and also insulinemia represent major signals in the short-term regulation of hunger and satiety. PMID- 27356206 TI - Are serum nitric oxide metabolites associated with fasting insulin among Iranian adults? (Tehran Lipid and Glucose Study). AB - AIM: It has been suggested that insulin resistance is associated with altered nitric oxide (NO) homeostasis. There is however no population-based study documenting an association between fasting serum insulin and serum NO metabolites (NOx) with multivariable adjustment. This study was therefore designed to determine the association between serum NOx and fasting insulin levels and insulin resistance/sensitivity indices in a sample of a population-based study in Iran. MATERIALS AND METHODS: This study, performed within the framework of the Tehran Lipid and Glucose Study (TLGS), analyzed the data of 1518 non-diabetic subjects (955 women), aged 20-87 years, who had participated in phase III of the TLGS (2006-2008). Serum NOx concentrations were measured using the Griess method. Fasting serum insulin was measured by the electrochemiluminescence immunoassay method. Multiple regression analysis was used to determine the association between serum NOx concentration and quartiles of insulin and insulin resistance/sensitivity indices (HOMA1-IR, HOMA2-IR, and QUICKI). RESULTS: NOx concentration in women only was weakly correlated with HOMA1-IR (r = 0.07, P = 0.03) and QUICKI (r = -0.07, P = 0.03), whereas no significant association was observed in men (P > 0.05). Marginally significant correlations were also found between serum NOx and fasting insulin concentration (r = 0.062, p = 0.057) and HOMA2-IR (r = 0.063, p = 0.053) in women. NOx concentration differed significantly between quartiles of insulin and insulin resistance/sensitivity indices among women and the total population (P < 0.05), associations which remained significant after age adjustment (P < 0.05), but not after adjustment for other confounding variables (P > 0.05). CONCLUSIONS: Fasting serum insulin level and insulin resistance/sensitivity indices are not associated with serum NOx level after multivariable adjustment. PMID- 27356207 TI - Bronsted Acid Catalyzed Addition of Enamides to ortho-Quinone Methide Imines-An Efficient and Highly Enantioselective Synthesis of Chiral Tetrahydroacridines. AB - The direct and highly enantioselective synthesis of tetrahydroacridines was achieved through the phosphoric acid catalyzed addition of enamides to in situ generated ortho-quinone methide imines and subsequent elimination. This novel one step process constitutes a very efficient, elegant, and selective synthetic approach to valuable N-heterocycles with a 1,4-dihydroquinoline motif. By subsequent highly diastereoselective hydrogenation and N-deprotection the reaction products were easily converted into free hexahydroacridines with a total of three new stereogenic centers. PMID- 27356208 TI - In silico designing of hyper-glycosylated analogs for the human coagulation factor IX. AB - N-glycosylation is a process during which a glycan moiety attaches to the asparagine residue in the N-glycosylation consensus sequence (Asn-Xxx-Ser/Thr), where Xxx can be any amino acid except proline. Introduction of a new N glycosylation site into a protein backbone leads to its hyper-glycosylation, and may improve the protein properties such as solubility, folding, stability, and secretion. Glyco-engineering is an approach to facilitate the hyper-glycosylation of recombinant proteins by application of the site-directed mutagenesis methods. In this regard, selection of a suitable location on the surface of a protein for introduction of a new N-glycosylation site is a main concern. In this work, a computational approach was conducted to select suitable location(s) for introducing new N-glycosylation sites into the human coagulation factor IX (hFIX). With this aim, the first 45 residues of mature hFIX were explored to find out suitable positions for introducing either Asn or Ser/Thr residues, to create new N-glycosylation site(s). Our exploration lead to detection of five potential positions, for hyper-glycosylation. For each suggested position, an analog was defined and subjected for N-glycosylation efficiency prediction. After generation of three-dimensional structures, by homology-based modeling, the five designed analogs were examined by molecular dynamic (MD) simulations, to predict their stability levels and probable structural distortions caused by amino acid substitutions, relative to the native counterpart. Three out of five suggested analogs, namely; E15T, K22N, and R37N, reached equilibration state with relatively constant Root Mean Square Deviation values. Additional analysis on the data obtained during MD simulations, lead us to conclude that, R37N is the only qualified analog with the most similar structure and dynamic behavior to that of the native counterpart, to be considered for further experimental investigations. PMID- 27356210 TI - A Tracheal Mass. PMID- 27356209 TI - Cirrhosis-related musculoskeletal disease: radiological review. AB - Musculoskeletal problems in patients with liver disease are common; however, they are not so well described in the literature. Therefore, there is a need to collate information on these disorders, as their incidence is on a constant rise and some of these pathologies can severely debilitate the patient's quality of life. These disorders are parietal wall varices with or without bleeding, spontaneous intramuscular haematoma (e.g. rectus sheath), abdominal wall hernia, anasarca, hepatic osteodystrophy, septic arthritis, osteomyelitis, necrotizing fasciitis, osseous metastases from hepatocellular carcinoma etc. While portal hypertension plays a key role in disorders, in others, dysregulation of the coagulation system or a compromised immune system are responsible. Imaging plays an essential role in the assessment of these complications and awareness of these musculoskeletal manifestations is vital for establishing a timely diagnosis and planning of appropriate therapy, as these disorders can significantly impact the morbidity and mortality and also influence candidacy for liver transplantation. We herein comprehensively appraise various musculoskeletal complications associated with chronic liver disease/liver cirrhosis especially from an imaging perspective which, to the best of our knowledge, have not been collectively described in English literature. PMID- 27356212 TI - Echoendoscopic ethanol ablation of tumor combined with celiac plexus neurolysis in patients with pancreatic adenocarcinoma. AB - BACKGROUND AND AIM: Endoscopic ultrasonography guided-celiac plexus neurolysis relieves pain in patients with pancreatic cancer but with often suboptimal and transient results. The study aims to compare the efficacy and safety of endoscopic ultrasound-guided tumor ethanol ablation combined with celiac plexus neurolysis with respect to celiac plexus neurolysis alone for pain management in patients with pancreatic cancer. METHODS: Among 123 patients with unresectable pancreatic cancer referred to our Institution between 2006 and 2014, 58 treated with endoscopic ultrasound-guided celiac plexus neurolysis (Group 1) and 65 with the combined approach (Group 2) were compared. Logistic regression models were applied to identify predictors of pain relief. RESULTS: The two groups presented similar baseline clinical and tumoral parameters. Pre-procedural visual analog scale score was 7 in both groups (P = 0.8), and tumor max diameter was 38 mm (range 25-59) in Group 1 and 43 mm (22-59) in Group 2 (P = 0.4). The combined treatment increased pain relief and complete pain response rate (P = 0.005 and 0.003, respectively). Median duration of pain relief was 10 (7-14) and 18 (13-20) weeks in the two groups, respectively (P = 0.004). At multivariate regression, initial visual analog scale score and endoscopic technique adopted resulted significantly associated with pain relief. No severe treatment-related adverse events were reported. Median overall survival was 6.5 months (5.1-8.6) in Group 1 and 8.3 months (6-11.4) in Group 2 (P = 0.05). CONCLUSIONS: Endoscopic ultrasound guided tumor ablation combined with celiac plexus neurolysis appears to be superior to celiac plexus neurolysis alone in terms of pain control and overall survival. PMID- 27356211 TI - Un Jalon, Un Volteon, y Otra Vez: High-Risk Crack Smoking Paraphernalia in Mexico City. AB - During the past decade, crack smoking has increased in Mexico among poor urban populations. Despite this increasing prevalence, little is known about the types of paraphernalia used and related sharing practices and physical harms. Data come from in-depth semi-structured interviews and observations with 156 current crack smokers in Mexico City. Findings reveal a complex, crack-smoking process in Mexico City that represents an interconnected structure of paraphernalia items and pipes that could contribute to detrimental health consequences. Specifically, we identify essential paraphernalia items that make the smoking of crack possible; describe the homemade construction of two categories of pipes; and detail the sharing practices and physical harms associated with these paraphernalia. Results point towards a smoking process that is embedded in impoverished urban neighborhoods sustained by an accessible street-level crack market. Discussed are the policy and intervention implications associated with reducing crack-related health consequences in Mexico and other Latin American countries. PMID- 27356213 TI - Fructokinase A acts as a protein kinase to promote nucleotide synthesis. PMID- 27356214 TI - Evolution of Na-S(-O) Compounds on the Cu2ZnSnS4 Absorber Surface and Their Effects on CdS Thin Film Growth. AB - Formation of Na-containing surface compounds is an important phenomenon in the Cu2ZnSnS4 (CZTS) quaternary material synthesis for solar cell applications. Still, identification of these compounds and the understanding of their potential influence on buffer layer growth and device performance are scarce. In this work, we discovered that the evolution of Na-S(-O) compounds on the CZTS surface substantially affect the solution/CZTS interface during the chemical bath deposition of CdS buffer film. We showed that Na2S negatively affects the growth of CdS, and that this compound is likely to form on the CZTS surface after annealing. It was also demonstrated that the Na2S compound can be oxidized to Na2SO4 by air exposure of the annealed CZTS surface or be removed using water dipping instead of the commonly used KCN etching process, resulting in significantly better quality of the CdS layer. Lastly, 6.5% CZTS solar cells were fabricated with air exposure treatment without incorporation of the KCN etching process. This work provides new insight into the growth of the CdS/CZTS interface for solar cell applications and opens new possibilities for improving likewise Cd free buffer materials that are grown with a similar chemical bath deposition process. PMID- 27356215 TI - Effect of elongational flow on immiscible polymer blend/nanoparticle composites: a molecular dynamics study. AB - Using coarse-grained nonequilibrium molecular dynamics, the dynamics of a blend of the equal ratio of immiscible polymers mixed with nanoparticles (NP) are simulated. The simulations are conducted under planar elongational flow, which affects the dispersion of the NPs and the self-assembly morphology. The goal of this study is to investigate the effect of planar elongational flow on the nanocomposite blend system as well as to thoroughly compare the blend to an analogous symmetric block copolymer (BCP) system to understand the role of the polymer structure on the morphology and NP dispersion. Two types of spherical NPs are considered: (1) selective NPs that are attracted to one of the polymer components and (2) nonselective NPs that are neutral to both components. A comparison of the blend and BCP systems reveals that for selective NP, the blend system shows a much broader NP distribution in the selective phase than the BCP phase. This is due to a more uniform distribution of polymer chain ends throughout the selective phase in the blend system than the BCP system. For nonselective NP, the blend and BCP systems show similar results for low elongation rates, but the NP peak in the BCP system broadens as elongation rates approach the order-disorder transition. In addition, the presence of NP is found to affect the morphology transitions of both the blend and BCP systems, depending on the NP type. PMID- 27356216 TI - The Sexual Possible Selves and Strategies of First-Semester College Students: What Do They Hope for and Fear and How Do They Plan to Get There? AB - The purpose of this study was to expand research on emerging adult sexuality by examining first-semester college students' (N = 282) possible selves and strategies related to sex, and by considering whether these varied by demographic characteristics. Students were first asked to describe what they expected and feared regarding sex and sexuality in the coming year and were then asked to articulate strategies for achieving goals and avoiding fears. Content analysis of participants' responses to open-ended questions revealed that expected possible selves commonly discussed included abstinence, interpersonal relationships, physical/sexual health, and exploration. Fears commonly discussed included reputation, risk-taking behaviors, and rape/assault. Categorical comparisons indicated abstinence and interpersonal relationships were the most prominent foci of expected sexual possible selves (SPS) and strategies, and physical/sexual health was the most prominent focus of feared SPS and strategies. Chi-square analyses indicated significant variations in SPS, feared selves, and strategies based on sex, intercourse experience, and relationship type. Binomial logistic regression analyses indicated religiosity differences in the SPS and strategies of abstinence, explore/experiment, physical/sexual health, interpersonal relationship, and risk-taking behaviors. Implications for research and sexual health education for college-based populations are discussed. PMID- 27356217 TI - On the Activation of Methane and Carbon Dioxide by [HTaO](+) and [TaOH](+) in the Gas Phase: A Mechanistic Study. AB - The thermal reactions of [Ta,O,H](+) with methane and carbon dioxide have been investigated experimentally and theoretically by using electrospray ionization mass spectrometry (ESI MS) and density functional theory calculations. Although the activation of methane proceeds by liberation of H2 , the activation of CO2 gives rise to the formation of [OTa(OH)](+) under the elimination of CO. Computational studies of the reactions of methane and carbon dioxide with the two isomers of [Ta,O,H](+) , namely, [HTaO](+) and [Ta(OH)](+) , have been performed to elucidate mechanistic aspects and to explain characteristic reaction patterns. PMID- 27356231 TI - A low-cost, ultraflexible cloth-based microfluidic device for wireless electrochemiluminescence application. AB - The rising need for low-cost diagnostic devices has led to the search for inexpensive matrices that allow performing alternative analytical assays. Cloth is a viable material for the development of analytical devices due to its low material and manufacture costs, ability to wick assay fluids by capillary forces, and potential for patterning multiplexed channel geometries. In this paper, we describe the construction of low-cost, ultraflexible microfluidic cloth-based analytical devices (MUCADs) for wireless electrochemiluminescence based on closed bipolar electrodes (C-WL-ECL), employing extremely cheap materials and a manufacturing process. The C-WL-ECL MUCADs are built with wax-screen-printed cloth channels and carbon ink screen-printed electrodes, and the estimated cost per device is only $0.015. To demonstrate the performance of C-WL-ECL MUCADs, the two most commonly used ECL systems - tris(2,2'-bipyridyl)ruthenium(ii)/tri-n propylamine (Ru(bpy)3(2+)/TPA) and 3-aminophthalhydrazide/hydrogen peroxide (luminol/H2O2) - are applied. Under optimized conditions, the C-WL-ECL method has successfully fulfilled the quantitative determination of TPA with a detection limit of 0.085 mM. In addition, on the bent MUCADs (bending angle (theta) = 180 degrees ), the luminol/H2O2-based ECL system can detect H2O2 as low as 0.024 mM. Based on such an ECL system, the bent MUCADs are further used for determination of glucose in a phosphate buffer solution (PBS), with the detection limit of 0.195 mM. Finally, the applicability and validity, anti-interference ability, and storage stability of the C-WL-ECL MUCADs are investigated. The results indicate that the proposed device has shown potential to extend the use of microfluidic analytical devices, due to its simplicity, low cost, ultraflexibility, and acceptable analytical performance. PMID- 27356232 TI - Conformational Changes and Flexibility of DNA Devices Observed by Small-Angle X ray Scattering. AB - Self-assembled DNA origami nanostructures enable the creation of precisely defined shapes at the molecular scale. Dynamic DNA devices that are capable of switching between defined conformations could afford completely novel functionalities for diagnostic, therapeutic, or engineering applications. Developing such objects benefits strongly from experimental feedback about conformational changes and 3D structures, ideally in solution, free of potential biases from surface attachment or labeling. Here, we demonstrate that small-angle X-ray scattering (SAXS) can quantitatively resolve the conformational changes of a DNA origami two-state switch device as a function of the ionic strength of the solution. In addition, we show how SAXS data allow for refinement of the predicted idealized three-dimensional structure of the DNA object using a normal mode approach based on an elastic network model. The results reveal deviations from the idealized design geometries that are otherwise difficult to resolve. Our results establish SAXS as a powerful tool to investigate conformational changes and solution structures of DNA origami and we anticipate our methodology to be broadly applicable to increasingly complex DNA and RNA devices. PMID- 27356233 TI - Alcoholic liver disease: focus on prodromal gut health. AB - Alcoholic liver disease (ALD) is implicated in gut disturbances, both functionally and structurally. It has been noticed that the gut-liver interaction is an important feature in the prevention of systemic inflammation as well as liver health. The optimal functioning of the gut-liver axis depends on gut health. Therefore, gut problems may be important for estimating liver inflammation, while our knowledge of ALD could also provide an insight into gut health. Gut problems accompanied by ALD include gut motility and absorption problems, mucosal damage and the dysbiosis of gut microbiota and gastrointestinal carcinogenesis. Moreover, there is emerging evidence that besides direct inflammatory injury caused by alcohol, gut problems related to ALD play a crucial role in the pathogenesis of cardiovascular and immunological disorders. In this regard, we should consider ALD in relation to both gut health and chronic systemic low-grade inflammation. Accordingly, integrative therapeutic strategies are warranted for treating and preventing ALD and systemic inflammation as well as alcohol-related gut problems. PMID- 27356234 TI - The first asymmetric synthesis of marliolide from readily accessible carbohydrate as chiral template. AB - A simple and efficient strategy for the first asymmetric total synthesis of marliolide was accomplished by using stereoselective alkylation of the dianion of the beta-hydroxy lactone enolate with myristyl aldehyde as a key step. The key intermediate, beta-hydroxyl gamma-methyl butyrolactone was prepared by transformation of L-lyxonolactone starting from D-ribose, a naturally abundant chiral carbohydrate. PMID- 27356235 TI - Extremely high boron tolerance in Puccinellia distans (Jacq.) Parl. related to root boron exclusion and a well-regulated antioxidant system. AB - Recent studies indicate an extremely high level of tolerance to boron (B) toxicity in Puccinellia distans (Jacq.) Parl. but the mechanistic basis is not known. Puccinellia distans was exposed to B concentrations of up to 1000 mg B L-1 and root B uptake, growth parameters, B and N contents, H2O2 accumulation and .OH scavenging activity were measured. Antioxidant enzyme activities including superoxide dismutase (SOD), ascorbate peroxidase, catalase, peroxidase and glutathione reductase, and lipid peroxidation products were determined. B appears to be actively excluded from roots. Excess B supply caused structural deformations in roots and leaves, H2O2 accumulation and simultaneous up regulation of the antioxidative system, which prevented lipid peroxidation even at the highest B concentrations. Thus, P. distans has an efficient root B exclusion capability and, in addition, B tolerance in shoots is achieved by a well-regulated antioxidant defense system. PMID- 27356237 TI - Can irisin be a linker between physical activity and brain function? AB - Irisin was initially discovered as a novel hormone-like myokine released from skeletal muscle during exercise to improve obesity and glucose dysfunction by stimulating the browning of white adipose tissue. Emerging evidence have indicated that irisin also affects brain function. FNDC5 mRNA and FNDC5/irisin immunoreactivity are present in various regions of the brain. Central irisin is involved in the regulation of neural differentiation and proliferation, neurobehavior, energy expenditure and cardiac function. Elevation of peripheral irisin level stimulates hippocampal genes related to neuroprotection, learning and memory. In this brief review, we summarize the current understanding on neuronal functions of irisin. In addition, we discuss the pros and cons for this molecule as a potential messenger mediating the crosstalk between skeletal muscle and central nervous system during exercise. PMID- 27356236 TI - High-throughput sequencing offers new insights into 5-hydroxymethylcytosine. AB - Chemical modifications of DNA comprise epigenetic mechanisms that contribute to the maintenance of cellular activities and memory. Although the function of 5 methylcytosine (5-mC) has been extensively studied, little is known about the function(s) of relatively rarer and underappreciated cytosine modifications including 5-hydroxymethylcytosine (5-hmC). The discovery that ten-eleven translocation (Tet) proteins mediate conversion of 5-mC to 5-hmC, and other oxidation derivatives, sparked renewed interest to understand the biological role of 5-hmC. Studies examining total 5-hmC levels revealed the highly dynamic yet tissue-specific nature of this modification, implicating a role in epigenetic regulation and development. Intriguingly, 5-hmC levels are highest during early development and in the brain where abnormal patterns of 5-hmC have been observed in disease conditions. Thus, 5-hmC adds to the growing list of epigenetic modifications with potential utility in clinical applications and warrants further investigation. This review discusses the emerging functional roles of 5 hmC in normal and disease states, focusing primarily on insights provided by recent studies exploring the genome-wide distribution of this modification in mammals. PMID- 27356238 TI - Modified Best-Practice Algorithm to Reduce the Number of Postoperative Videofluoroscopic Swallow Studies in Patients With Type 1 Laryngeal Cleft Repair. AB - IMPORTANCE: There is no consensus as to the timing of videofluoroscopic swallow studies (VFSSs) in determining resolving aspiration after laryngeal cleft repair. There is a growing literature on the effect of radiation exposure in children. OBJECTIVE: To modify a previously published best-practice algorithm based on a literature review and our clinical experience to maintain the quality of care provided after successful type 1 laryngeal cleft repair, while reducing the total number of postoperative VFSSs by 10% or greater. DESIGN, SETTING, AND PARTICIPANTS: The previously published algorithm was modified by a multidisciplinary group at a tertiary care academic medical center (Massachusetts Eye and Ear) and was prospectively applied to 31 children who underwent type 1 laryngeal cleft repair from January 1, 2013, to February 28, 2015. MAIN OUTCOMES AND MEASURES: The number of VFSSs obtained in the first 7 months after surgery was compared with the peer-reviewed literature and with a retrospective cohort of 27 patients who underwent type 1 laryngeal cleft repair from January 1, 2008, to December 31, 2012. RESULTS: The study cohort comprised 31 patients. Their ages ranged from 10 to 48 months, with a mean (SD) age of 23.94 (9.93) months, and 19% (6 of 31) were female. The mean (SD) number of postoperative VFSSs per patient before and after implementation of the algorithm was 1.22 (0.42) and 1.03 (0.55), respectively. The use of the algorithm reduced the number of VFSSs by 0.19 (95% CI, -0.07 to 0.45). This reduction in radiation exposure is equivalent to 1.47 chest radiographs per child per course of care. Surgical success was 87% (27 of 31) compared with our group's previously published success rate of 78% (21 of 27) (absolute difference, 0.09; 95% CI, -0.17 to 0.34). CONCLUSIONS AND RELEVANCE: This modified algorithm to help guide decisions on when and how often to obtain VFSSs after type 1 laryngeal cleft repair can limit patients' radiation exposure, while maintaining high surgical success rates. PMID- 27356239 TI - Antimelanogenesis Activity of Hydrolyzed Ginseng Extract (GINST) via Inhibition of JNK Mitogen-activated Protein Kinase in B16F10 Cells. AB - GINST is a hydrolyzed ginseng extract produced by an in vitro process that imitates the metabolic function of bacteria in the human digestive track and has approved by the Ministry of Food and Drug Safety of Korea for the management of postprandial hyperglycemia. Additionally, GINST has been reported to have other physiological functions including anti-aging and antioxidant effects. The objectives of this study are to compare the antimelanogenic effects of fresh ginseng extract (FGE) and GINST extract and to elucidate the functional mechanism. The concentration of total ginsenosides in FGE and GINST was measured using ultraperformance liquid chromatography with a C18 column. B16F10 cells were treated with FGE and GINST for 72 h to assess melanin content, tyrosinase activity, and protein levels of microphthalmia-associated transcription factor (MITF) and tyrosinase-related protein-1 (TRP-1). The activity of kinases involved in mitogen-activated protein kinase (MAPK) signaling, such as extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 mitogen activated protein kinases (p38), were measured using western blots. While neither FGE nor GINST inhibited the activity of mushroom tyrosinase directly, GINST decreased melanogenesis and tyrosinase activity markedly. Furthermore, our results indicate that GINST downregulated the levels of MITF and TRP-1 possibly by suppressing JNK signaling. We concluded that, when compared to FGE, GINST has a superior antimelanogenic effect mediated by the downregulation of MITF, TRP-1, and intracellular tyrosinase activity via the JNK signaling pathway. Thus, we suggest that GINST has the potential to be used as a novel skin whitening agent. PMID- 27356241 TI - The burden of filial piety: A qualitative study on caregiving motivations amongst family caregivers of patients with cancer in Singapore. AB - OBJECTIVE: This study explores (1) the motivations and challenges facing family caregiving for cancer in Singapore and (2) suggests a possible framework to guide culturally sensitive future work on caregivers. DESIGN: Twenty caregivers of patients being treated for cancer at a public hospital in Singapore were interviewed. A semi-structured interview format and inductive thematic analysis were used to analyse the data. Caregivers were asked about their motivations for caregiving and the challenges they faced. RESULTS: Caregivers' motivations grouped into three categories: personal value and fulfilment, giving care because of societal expectations such as filial piety, and practical need. Challenges were grouped into interpersonal challenges, disclosure and finding balance. Caregivers with different primary motivations varied in their responses to these challenges. More autonomous caregivers cited learning points and reprioritised more effectively than less autonomous caregivers, who reported more internal conflict and less control over their situation. CONCLUSIONS: In Singapore and Asia, sociocultural values of family caregiving are not uniformly experienced as positive, and may be burdensome for caregivers who give care primarily for extrinsic motivations. As family caregiving needs increase, targeted psychosocial support for caregivers with less autonomous behavioural orientations may pre-empt caregiver burnout and burden. PMID- 27356240 TI - Dietary supplementation with omega-3 fatty acids and oleate enhances exercise training effects in patients with metabolic syndrome. AB - OBJECTIVE: We studied the effects of exercise training alone or combined with dietary supplementation of omega-3 polyunsaturated fatty acids (Omega-3PUFA) and oleate on metabolic syndrome (MSyn) components and other markers of cardiometabolic health. METHODS: Thirty-six patients with MSyn underwent 24 weeks of high-intensity interval training. In a double-blind randomized design, half of the group ingested 500 mL/day of semi-skim milk (8 g of fat; placebo milk) whereas the other half ingested 500 mL/day of skim milk enriched with 275 mg of Omega-3PUFA and 7.5 g of oleate (Omega-3 + OLE). RESULTS: Omega-3 + OLE treatment elevated 30% plasma Omega-3PUFA but not significantly (P = 0.286). Improvements in VO2peak (12.8%), mean blood pressure (-7.1%), waist circumference (-1.8%), body fat mass (-2.9%), and trunk fat mass (-3.3%) were similar between groups. However, insulin sensitivity (measured by intravenous glucose tolerance test), serum concentration of C-reactive protein, and high-density lipoprotein improved only in the Omega-3 + OLE group by 31.5%, 32.1%, and 10.3%, respectively (all P < 0.05). Fasting serum triacylglycerol, glucose, and plasma fibrinogen concentrations did not improve in either group after 24 weeks of intervention. CONCLUSIONS: Diet supplementation with Omega-3PUFA and oleate enhanced cardiometabolic benefits of intense aerobic exercise training in patients with MSyn. PMID- 27356242 TI - Aggression Is Associated With Increased Anabolic-Androgenic Steroid Use Contemplation Among Adolescents. AB - We investigated the relationship between aggression and anabolic-androgenic steroid (AAS) use intent among adolescents. A nationally representative sample of Norwegian 18-year-olds (N = 1,334, females = 58.7%) took part in a survey in 2013 (response rate = 64.9%). Participants completed the physical and verbal subscales of the Short-Form Buss-Perry Aggression Questionnaire, the Intent to use AAS Scale, the Alcohol Use Disorders Identification Test-Consumption, and the Hospital Anxiety and Depression Scale. They also provided demographic information and answered questions about AAS use, gambling participation, as well as cigarette and snus use. Descriptive statistics and multinomial logistic regression were used to analyze the data. Lifetime and past year prevalence of AAS use was 0.1%. Between 0.4% and 1.7% of participants disclosed intent to use while between 1.1% and 2.5% expressed neutral intent to initiate AAS use. Compared to persons low on aggression, individuals high on aggression were more likely to report intent and curiosity towards initiating AAS use. Our findings indicate that aggression is a risk factor for AAS use contemplation among adolescents. PMID- 27356243 TI - Dermoscopic criteria and basal cell carcinoma. AB - Basal cell carcinoma (BCC) is nowadays the most frequent skin cancer in the fair skinned population. Clinical suspicion for BCC diagnosis can be easy in advance cases, but it sometimes sets a real challenge wherein dermoscopy has proven to be a useful tool. Dermoscopy is a non-invasive diagnostic technique that improves the clinical diagnosis of pigmented and non-pigmented BCC representing a link between macroscopic clinical dermatology and microscopic dermatopathology. The dermoscopy of basal cell carcinoma is currently very well-known, as well as the clinical and histopathological features of BCC subtypes. Recently some flowcharts and algorithms for the most common subtypes of BCC have been proposed. We review the latest literature on the topic to describe the most frequent dermoscopy patterns for each subtype. PMID- 27356244 TI - Extended Bis(benzothia)quinodimethanes and Their Dications: From Singlet Diradicaloids to Isoelectronic Structures of Long Acenes. AB - Extended bis(benzothia)quinodimethanes and their dications were synthesized as stable species. The neutral compounds mainly have a quinoidal structure in the ground state but show increased diradical character with extension of the central quinodimethane unit. The dications exhibit similar electronic absorption spectra, NMR spectra, NICS values, and diatropic ring currents to their aromatic all carbon acene analogues and thus can be regarded as genuine isoelectronic structures of pentacene, hexacene, and heptacene, respectively. Our research gave some insights into the design and synthesis of stable longer acene analogues. PMID- 27356245 TI - ERRATA AB - [This corrects the article DOI: 10.1590/S0104-59702016005000010.]. PMID- 27356246 TI - The challenge of the increasing demand for joint replacement. PMID- 27356247 TI - Zika virus threat. PMID- 27356248 TI - Burden of disease from second-hand smoke exposure in New Zealand. AB - AIM: To estimate the number of deaths and disability-adjusted life years (DALYs) attributable to secondhand smoke in New Zealand. METHOD: Comparative risk assessment methods were used to estimate the attributable burden from second-hand smoke in children and non-smoking adults in New Zealand. Disease outcomes included were: ischaemic heart disease; stroke and lung cancer in adults; asthma; lower respiratory infections; otitis media; sudden unexpected death in infancy (SUDI); and low birthweight at term in children. Mortality data from 2009-2011 and DALY data from 2006 were used. RESULTS: In New Zealand, second-hand smoke was estimated to have caused 104 deaths (plausible range: 66-137) in 2010, and led to the loss of 2,286 healthy years of life (DALYs) (1,465-3,177) in 2006. The main conditions accounting for this health burden were ischaemic heart disease and stroke in older adults. Children accounted for 34% of the attributable health loss in 2006, particularly due to SUDI. Maori experienced five times the health loss of non-Maori, after standardising for age differences. CONCLUSION: Second hand smoke continues to cause substantial health loss in New Zealand, and disproportionately affects children and Maori. Substantial health gains can be made by reducing exposure to second-hand smoke in New Zealand. PMID- 27356249 TI - The Impact on Life questionnaire: validation for elective surgery prioritisation in New Zealand prioritisation criteria in orthopaedic surgery. AB - AIM: This cohort study tested the reliability and validity of the Impact on Life (IoL) patient-rated questionnaire for use in prioritising orthopaedic procedures. METHODS: Three hundred and twenty-four patients completed the questionnaire during specialist orthopaedic assessments over a 5-month period in 2013. The reliability and validity of the IoL were tested against the SF-12 and Oxford scores. Correlation analysis was used to assess patient- and surgeon-rated scores. Internal consistency reliability was assessed using Cronbach's alpha. Patient- and surgeon-rated scores were further analysed between patients added to the waiting list and those that were not. RESULTS: Participants' mean age was 58 years (range 18-88). Reliability analysis showed the IoL had excellent internal consistency with a Cronbach's alpha of 0.926, reaching the threshold for clinical application. Construct validity of the IoL was confirmed with significant correlation with other validated quality of life measures (p<0.01). T-tests indicated that patients placed on the waiting list had significantly higher surgeon and IoL scores (p<0.001), compared with those not placed on the waiting list. CONCLUSION: Our results support the IoL as a valid and reliable method of assessing patient-rated quality of life and recommend its use in the Orthopaedic Clinical Priority Assessment Criteria score. PMID- 27356250 TI - Perioperative mortality in New Zealand related to hip and knee replacement surgery: comparing administrative and registry data. AB - INTRODUCTION: Perioperative mortality is of considerable importance, but few national assessments are available. New Zealand has a clinical registry and an administrative dataset that both capture national information about hip and knee arthroplasties. National perioperative mortality rates were compared between the two data sources. METHOD: Data related to all patients undergoing an elective hip or knee replacement procedure (primary or revision) between 1 January 2007 and 31 December 2011 were separately extracted from the New Zealand Joint Registry and the National Minimum Dataset. The procedure date was used to define the occurrence of an event and dates were compared between datasets plus or minus 3 days. Date of death information was obtained from the National Mortality Collection and used to estimate 30 day mortality rates. RESULTS: No statistically significant differences in perioperative mortality were evident between comparisons from the two data sources although more deaths were recorded among Registry-only procedures. CONCLUSIONS: Estimates of 30 day perioperative mortality related to hip and knee arthroplasty procedures in New Zealand 2007 2011 are very similar regardless of data source. These data, coupled with perioperative mortality review using structured reports obtained from clinicians, could be used to develop a surveillance system to promote surgical safety. PMID- 27356251 TI - Cascade of care for people living with HIV infection in the Wellington region. AB - AIM: Antiretroviral therapy (ART) is highly effective in providing better outcomes for people living with HIV infection (PLHIV) and reducing the risk of transmission to others. The 'cascade of care' describes steps in delivering care: diagnosis, linkage and retention in care, and the provision and success of ART. METHODS: The cascade of care for PLHIV in the Wellington region was reviewed during 2015. An estimate of 20% undiagnosed HIV infection was used from past New Zealand research. 'Suppression of HIV infection' by ART was defined as a viral load less than 200 RNA copies/mL as commonly used in other cascade of care studies. RESULTS: There were 307 people identified with HIV infection. The median age was 48 years, and 54 (18%) were women. At the time of the audit, each of the 307 PLHIV were accounted for and not lost to follow-up. ART was being taken by 272 (89%). Those with a CD4 count >500 x 10^6/L accounted for 26/35 not on ART. Of those on ART 254/272 (93.3%) had a suppressed viral load, including 252/259 (97.3%) of those established on treatment >6 months. Overall, 254/384 (66.1%) were estimated to have a suppressed viral load. CONCLUSIONS: The study indicated a high level of retention in care, and of effective HIV suppression, with ART. The main gaps in the cascade of care were the people with undiagnosed HIV infection and those in whom treatment had not yet been initiated because their CD4 count was above 500 cells/10^6/L. PMID- 27356252 TI - Excess cost associated with primary hip and knee joint arthroplasty surgical site infections: a driver to support investment in quality improvement strategies to reduce infection rates. AB - AIM: To determine the excess costs attributable to surgical site infections (SSI) following primary hip and knee joint arthroplasty at Auckland City Hospital. METHODS: A retrospective case-control study. Cases were patients who developed a SSI following primary hip (THA) and knee arthroplasty (TKA) surgery within 90 days of the procedure. Cases were matched 1:2 with controls; patients whose primary hip and knee arthroplasty procedures were not complicated by infection. Controls were matched for age, gender, date of surgery, type of surgery, and ASA category. The length of stay (LOS) and hospital costs for the initial admission and subsequent readmission for infection were calculated from the clinical costing system at Auckland District Health Board. RESULTS: Eleven cases were identified; 3 following TKA, 7 following THA, and 1 following hemiarthroplasty of the hip. Infections were classified as superficial, 1, joint space, 1, and deep incisional, 9. Five SSI were identified during the initial admission for joint arthroplasty and 6 patients were readmitted with an SSI. Compared to the control patients, SSIs were associated with an excess mean cost of $40,121 and an excess mean LOS of 42 days. CONCLUSIONS: There is a significant increase in LOS and cost associated with SSI following primary THA and TKA at Auckland City Hospital. In addition to the excess cost associated with SSI, there are also opportunity costs resulting from their impact on elective surgical waiting lists. This reinforces the significant positive economic impact a successful strategy to reduce SSIs associated with primary joint arthroplasty procedures will have. PMID- 27356253 TI - Rationing of hip and knee replacement: effect on the severity of patient-reported symptoms and the demand for surgery in Otago. AB - AIM: A key Government health target has been to increase access to elective surgery. Despite this, there is a growing concern about unmet demand and increasing numbers of patients are being declined elective surgery. This study aims to determine whether there has been an increase in the severity of osteoarthritis of the hip and knee in patients undergoing publicly-funded elective total joint replacement (TJR) and any increase in demand for TJR in Otago. METHOD: Demographic details and preoperative patient reported outcome scores (Oxford hip or knee score (OHS,OKS) and a reduced Western Ontario and McMaster Osteoarthritis Index (WOMAC) score (RWS) were collected prospectively in an historical cohort of patients undergoing total hip and knee replacement (THR, TKR) between 2006-2010. These were compared with all patients undergoing THR and TKR in the 12-month period commencing 1 November 2013, and all patients waitlisted during this period but returned to GP due to capacity issues. An estimate of current demand was made by adding all waitlisted public patients from the 12-month period to surgical numbers from private and those funded by ACC. RESULTS: In the 2006-2010 group of 613 patients, the mean OHS was 13.6 (SD 6.7) and OKS 15.4 (SD 6.5) and RWS 30.5 (SD 8.0). Three hundred and sixty-seven patients who underwent surgery in 2013/4 had significantly poorer scores (OHS 9.9 (SD 4.9), OKS 10.6 (SD 3.8), RWS 34.8 (SD 6.7)). The scores of 194 patients returned to GP in 2013/4 were the same as the historical surgical group (OHS13.0 (SD 6.2, OKS 15.2 (SD 5.9), RWS 30.8 (SD 8.4)). Six hundred and eight patients were wait-listed for public surgery and 356 joints were performed in private or under ACC in the 12-month period. The current intervention rate in Otago is 371/100,000 per year, while the demand has risen from 417/100000 in 2010-12 to 494/100,000 per year. In 2014, the shortfall was 241 joints per year. CONCLUSION: Patients undergoing primary elective total hip and knee replacement in Otago in 2014 are more severely disabled than between 2006-2010. Patients currently being returned to GP would have qualified for publicly funded surgery during that period. The demand for elective TJR in Otago has increased by 19% since 2012. PMID- 27356254 TI - Very low-carbohydrate diets in the management of diabetes revisited. AB - Humans can derive energy from carbohydrate, fat, or protein. The metabolism of carbohydrate requires by far the highest secretion of insulin. The central pathology of diabetes is the inability to maintain euglycaemia because of a deficiency in either the action or secretion of insulin. That is, because of either insulin resistance often accompanied by hyperinsulinaemia, or insulin deficiency caused by pancreatic beta cell failure. In individuals dependent on insulin and other hypoglycaemic medication, the difficulty of matching higher intakes of carbohydrates with the higher doses of medication required to maintain euglycaemia increases the risk of adverse events, including potentially fatal hypoglycaemic episodes. Thus, mechanistically it has always made sense to restrict carbohydrate (defined as sugar and starch, but not soluble and insoluble fibre) in the diets of people with diabetes. Randomised clinical trials have confirmed that this action based on first principles is effective. The continued recommendation of higher-carbohydrate, fat-restricted diets has been criticised by some scientists, practitioners and patients. Such protocols when compared with very low-carbohydrate diets provide inferior glycaemic control, and their introduction and subsequent increase in carbohydrate allowances has never been based on strong evidence. The trend towards highercarbohydrate diets for people with diabetes may have played a part in the modern characterisation of type 2 diabetes as a chronic condition with a progressive requirement for multiple medications. Here we will introduce some of the evidence for very low carbohydrate diets in diabetes management and discuss some of the common objections to their use. PMID- 27356256 TI - Case of takotsubo cardiomyopathy in a patient with COPD. PMID- 27356255 TI - Regulating tobacco retail in New Zealand: what can we learn from overseas? AB - Despite New Zealand's reputation as a leader in tobacco control, the retail environment for tobacco is relatively unregulated, particularly when compared to the licensing regimes for alcohol products and psychoactive substances (eg, synthetic cannabis and other 'legal highs'). There are currently no restrictions on who can sell tobacco, nor where it can be sold. The lack of an accurate tobacco retail register presents a challenge for those enforcing retail legislation. This paper summarises tobacco retail licensing schemes implemented in overseas jurisdictions, as these represent precedents on which New Zealand policies could be based. We also review how effective these schemes might be as part of a comprehensive tobacco control strategy. We conclude that a positive licensing scheme could increase compliance with existing smokefree legislation, and enable the introduction of further measures to control the supply of tobacco. Reducing tobacco availability is an important part of the range of interventions needed to achieve a smokefree New Zealand, and we urge the Government to redress the lack of progress in this area. PMID- 27356257 TI - Recent submissions to the New Zealand Government Health Select Committee on end of-life choices. PMID- 27356258 TI - Possible toxicity of olive leaf extract in a dietary supplement. PMID- 27356259 TI - Assessing the response to follow-up recommendations in radiology reports. PMID- 27356260 TI - Chronic misleading online advertising by chiropractors. PMID- 27356261 TI - Could New Zealand's law on "New Psychoactive Substances" provide lessons for achieving the Smokefree 2025 Goal? PMID- 27356262 TI - Zombie pandemic preparedness: a cautionary observation. PMID- 27356263 TI - Supramolecular Self-Assembly of Histidine-Capped-Dialkoxy-Anthracene: A Visible Light-Triggered Platform for Facile siRNA Delivery. AB - Supramolecular self-assembly of histidine-capped-dialkoxy-anthracene (HDA) results in the formation of light-responsive nanostructures. Single-crystal X-ray diffraction analysis of HDA shows two types of hydrogen bonding. The first hydrogen bond is established between the imidazole moieties while the second involves the oxygen atom of one amide group and the hydrogen atom of a second amide group. When protonated in acidic aqueous media, HDA successfully complexes siRNA yielding spherical nanostructures. This biocompatible platform controllably delivers siRNA with high efficacy upon visible-light irradiation leading up to 90 % of gene silencing in live cells. PMID- 27356264 TI - Clinical outcome after enteroscopy for small bowel angioectasia bleeding: A Korean Associateion for the Study of Intestinal Disease (KASID) multiceter study. AB - BACKGROUND AND AIMS: Angioectasias are the most common sources of bleeding in the small bowel. They can be treated using balloon-assisted enteroscopy (BAE). This study aimed to identify the rebleeding rate and associated factors after BAE in patients with small bowel angioectasia bleeding. METHODS: We retrospectively analyzed the records of patients with bleeding due to small bowel vascular lesion in a multicenter enteroscopy database including 1108 BAEs. Finally, in rebleeding analysis, we analyzed 66 patients with angioectasia on the basis of the Yano Yamamoto classification. Patients who had undergone endotherapy (ET) were divided into ET (n = 45) and non-ET (n = 21) groups. Rebleeding was defined as evidence of bleeding at least 30 days after BAE. RESULTS: Fifty-three patients (80.4%) underwent only one-side enteroscopy. The most common ET was argon plasma coagulation (87.2%). During a mean follow-up duration of 24.5 months, ET and non ET groups had rebleeding rates of 15.6% and 38.1% (P = 0.059), respectively. Median rebleeding time of ET and non-ET groups was 32.5 and 62 months, respectively. Liver cirrhosis (LC), low platelet count (< 105 /MUL), and transfusions were the rebleeding-associated factors in the univariate analysis. In the multivariate analysis, the presence of LC (HR 4.064, 95% CI 1.098-15.045; P = 0.036) was the only independent rebleeding-associated risk factor. CONCLUSIONS: ET using BAE did not significantly affect the rebleeding rate in patients with small bowel angioectasia bleeding. An independent rebleeding risk factor was the presence of LC. Regardless of ET, careful long-term follow-up may be needed, especially in LC patients with small bowel angioectasia bleeding. PMID- 27356265 TI - Novel IGH and MYC Translocation Partners in Diffuse Large B-Cell Lymphomas. AB - Chromosomal translocations involving an immunoglobulin (IG) locus and a proto oncogene play a major role in diffuse large B-cell lymphoma (DLBCL) pathogenesis. Recurrent IG translocation partners in DLBCL are the BCL6, BCL2, and MYC genes, but other rare translocation partners are also known. We studied 20 DLBCL with fluorescence in situ hybridization-based evidence for IG heavy chain (IGH) locus associated translocations not involving BCL6, BCL2, MALT1, or MYC by long distance inverse PCR to identify the translocation partners. Moreover, we studied eight DLBCL with MYC translocations not involving IG or known non-IG loci as translocation partner to search for novel MYC translocations. We identified three novel IGH-associated translocations. Chromosomal breakpoints involved the IMMP2L gene in 7q31, the BCAS2 gene in 1p13, and the PVRL2 gene in 19q13. The latter gene, which is recurrently translocated in T-cell lymphomas, is significantly higher expressed in the biopsy with the translocation compared to cases without this genetic aberration, indicating a pathogenetic role of PVRL2 also in DLBCL. In one case with a MYC break we obtained a novel MYC-SOCS1 translocation representing an unusual translocation of a proto-oncogene with a tumor suppressor gene. Indeed, we demonstrate that the oncogene was deregulated and the tumor suppressor gene inactivated. As both genes undergo aberrant somatic hypermutation in the region of the chromosomal breakpoints, this translocation likely happened as a byproduct of the hypermutation process. Overall, our study suggests that chromosomal translocations in DLBCL are more heterogeneous than previously known. (c) 2016 Wiley Periodicals, Inc. PMID- 27356266 TI - Sensing Glucose in Urine and Serum and Hydrogen Peroxide in Living Cells by Use of a Novel Boronate Nanoprobe Based on Surface-Enhanced Raman Spectroscopy. AB - Hydrogen peroxide (H2O2) is known as a key molecule in a variety of biological processes, as well as a crucial byproduct in many enzymatic reactions. Therefore, being able to selectively and sensitively detect H2O2 is not only important in monitoring, estimating, and decoding H2O2 relevant physiological pathways but also very helpful in developing enzymatic-based biosensors for other analytes of interest. Herein, we report a plasmonic probe for H2O2 based on 3 mercaptophenylboronic acid (3-MPBA) modified gold nanoparticles (AuNPs) which is coupled with surface-enhanced Raman scattering (SERS) to yield a limit of detection (LOD) of 70 nM. Our probe quantifies both exogenous and endogenous H2O2 levels in living cells and can further be coupled with glucose oxidase (GOx) to achieve quantitative and selective detection of glucose in artificial urine and human serum. PMID- 27356267 TI - Ca(2+)-activated chloride channel activity during Ca(2+) alternans in ventricular myocytes. AB - Cardiac alternans, defined beat-to-beat alternations in contraction, action potential (AP) morphology or cytosolic Ca transient (CaT) amplitude, is a high risk indicator for cardiac arrhythmias. We investigated mechanisms of cardiac alternans in single rabbit ventricular myocytes. CaTs were monitored simultaneously with membrane currents or APs recorded with the patch clamp technique. A strong correlation between beat-to-beat alternations of AP morphology and CaT alternans was observed. During CaT alternans application of voltage clamp protocols in form of pre-recorded APs revealed a prominent Ca(2+) dependent membrane current consisting of a large outward component coinciding with AP phases 1 and 2, followed by an inward current during AP repolarization. Approximately 85% of the initial outward current was blocked by Cl(-) channel blocker DIDS or lowering external Cl(-) concentration identifying it as a Ca(2+) activated Cl(-) current (ICaCC). The data suggest that ICaCC plays a critical role in shaping beat-to-beat alternations in AP morphology during alternans. PMID- 27356269 TI - Conformational Transformations in Aromatic Nitroso Oxides. AB - A systematic theoretical study on conformational transformations of monosubstituted (ortho- and para-) aromatic nitroso oxides R-C6H4NOO was performed. The existence of two rotation axes enables two types of conformational transitions in substituted arylnitroso oxides: trans/cis (rotation around the N-O bond) and syn/anti (rotation around the C-N bond, which is important in ortho isomers). The complete set of conformers was localized for R-C6H4NOO using four selected density functional (M06-L, mPWPW91, OLYP, and HCTH) and augmented polarization basis set of triple splitting. It was found that the activation enthalpy of the trans-cis conformational transition is nearly insensitive to the nature of R and ranges within 58-60 kJ/mol for para isomers. The ortho substituent has an insignificant effect on DeltaH(?)trans->cis: it increases this value by ~5 kJ/mol in syn isomers and decreases it by ~3 kJ/mol in anti isomers. On the contrary, the syn-anti conformational barrier is considerably affected by the substituent R; an increase in the electron-withdrawing properties of R decreases DeltaH(?)syn->anti. The activation enthalpies grow with increasing polarity of the solvent, as it was found using IEFPCM calculation. The values of relaxation time for all conformational equilibria were calculated and compared with known lifetimes of aromatic nitroso oxides. Our results suggest that syn/anti transitions occur fast enough in the scale of the experimental lifetime. However, trans/cis transformations proceed more slowly. And under certain conditions discussed in the paper, the rate of this conformational transition limits that of irreversible decay of nitroso oxide. PMID- 27356268 TI - Environmental Photochemistry of Altrenogest: Photoisomerization to a Bioactive Product with Increased Environmental Persistence via Reversible Photohydration. AB - Despite its wide use as a veterinary pharmaceutical, environmental fate data is lacking for altrenogest, a potent synthetic progestin. Here, it is reported that direct photolysis of altrenogest under environmentally relevant conditions was extremely efficient and rapid (half-life ~25 s). Photolysis rates (observed rate constant kobs = 2.7 +/- 0.2 * 10(-2) s(-1)) were unaffected by changes in pH or temperature but were sensitive to oxygen concentrations (N2-saturated kobs = 9.10 +/- 0.32 * 10(-2) s(-1); O2-saturated kobs = 1.38 +/- 0.11 * 10(-2) s(-1)). The primary photoproduct was identified as an isomer formed via an internal 2 + 2 cycloaddition reaction; the triplet lifetime (8.4 +/- 0.2 MUs) and rate constant (8 * 10(4) s(-1)) of this reaction were measured using transient absorption spectroscopy. Subsequent characterization determined that this primary cycloaddition photoproduct undergoes photohydration. The resultant photostable secondary photoproducts are subject to thermal dehydration in dark conditions, leading to reversion to the primary cycloaddition photoproduct on a time scale of hours to days, with the photohydration and dehydration repeatable over several light/dark cycles. This dehydration reaction occurs more rapidly at higher temperatures and is also accelerated at both high and low pH values. In vitro androgen receptor (AR)-dependent gene transcriptional activation cell assays and in silico nuclear hormone receptor screening revealed that certain photoproducts retain significant androgenic activity, which has implications for exposure risks associated with the presence and cycling of altrenogest and its photoproducts in the environment. PMID- 27356270 TI - Infrared and Raman Spectroscopy of Methylcyanodiacetylene (CH3 C5 N). AB - A spectroscopic study combining IR absorption and Raman scattering is presented for methylcyanodiacetylene (CH3 C5 N). Gas-phase, cryogenic matrix-isolated, and pure solid-phase substance was analyzed. Out of 16 normal vibrational modes, 14 were directly observed. The analysis of the spectra was assisted by quantum chemical calculations of vibrational frequencies, IR absorption intensities, and Raman scattering activities at density functional theory and ab initio levels. Previous assignments of gas-phase IR absorption bands were revisited and extended. PMID- 27356271 TI - Comparative persistence and adherence with newer anti-hyperglycemic agents to treat patients with type 2 diabetes in the United States. AB - OBJECTIVES: Non-adherence and non-persistence to anti-hyperglycemic agents are associated with worse clinical and economic outcomes in patients with type 2 diabetes. This study evaluated treatment persistence and adherence across newer anti-hyperglycemic agents (canagliflozin, dapagliflozin, sitagliptin, saxagliptin, linagliptin, liraglutide, or exenatide). METHODS: This retrospective cohort study of Truven Health Analytics Marketscan databases included adult patients with type 2 diabetes whose first pharmacy claim for a newer anti hyperglycemic agent was between February 1, 2014 and July 31, 2014. Treatment persistence and adherence were assessed for 12 months after the first claim (post index). Persistence was defined as no gap >=90 days between the end of one pharmacy claim and the start of the next pharmacy claim post-index. Adherence used two definitions: proportion of days covered (PDC) and medication possession ratio (MPR). Multivariable analyses of non-persistence (hazard ratios) and adherence (odds ratios) were adjusted for baseline demographics, drug cost, clinical characteristics, and other anti-hyperglycemic agents. RESULTS: A total of 11,961 patients met all study selection criteria. Persistence rates at 12 months were significantly greater (p < 0.05 for each comparison) for canagliflozin 100 mg (61%) compared with dapagliflozin 5 mg (40%), dapagliflozin 10 mg (41%), sitagliptin (48%), saxagliptin (42%), linagliptin (52%), liraglutide (47%), exenatide (23%), and long-acting exenatide (39%). The persistence rate was greater (p < 0.05) for canagliflozin 300 mg (64%) vs canagliflozin 100 mg. Median adherence rates for canagliflozin 100 mg (MPR = 0.83; PDC = 0.79) and canagliflozin 300 mg (MPR = 0.92; PDC = 0.81) were greater than for the other index anti-hyperglycemic agents (MPR = 0.33-0.75; PDC = 0.33-0.72). Consistent results for treatment persistence and adherence were observed in multivariable analyses that were adjusted baseline characteristics. CONCLUSIONS: Canagliflozin was associated with better treatment persistence and treatment adherence compared with other anti-hyperglycemic agents in real-world settings. PMID- 27356273 TI - Implementing psychological therapies for functional GI disorders in children and adults. AB - INTRODUCTION: Functional GI disorders (FGIDs) are common in adults and children. Psychological factors play an important role in the onset and maintenance of FGIDs and in explaining the associated disability. Psychological treatments such as Cognitive Behavioral Therapy and Hypnotherapy have been found efficacious in FGIDs but Integrating psychological treatments into traditionally medically oriented care can be challenging. AREAS COVERED: This review outlines the case for integrating psychological therapies into medical care for FGIDs and examine various models of integrated care that can be adapted to fit specific practice scenarios. Expert commentary: We advise integrating a psychologist in the care and treatment planning of every patient. Clinic-specific needs dictate how integrated care for patients with FGIDs can be delivered. PMID- 27356272 TI - The Interactive Influence of Cannabis-Related Negative Expectancies and Coping Motives on Cannabis Use Behavior and Problems. AB - OBJECTIVES: The present study tested whether coping motives for cannabis use moderate the effect of negative expectancies on cannabis use. METHODS: Participants were 149 (36.2% female, 61.59% non-Hispanic Caucasian) current cannabis users aged 18-36 (M = 21.01, SD = 3.09) who completed measures of cannabis-related expectancies and motives for use. Hierarchical multiple regressions were employed to investigate the predictive value of the interaction between negative expectancies and coping motives on cannabis use outcomes. RESULTS: Results revealed interactions between negative expectancies and coping motives with respect to past 90 day cannabis use frequency and cannabis problems. Global negative effects expectancies were associated with less frequent cannabis use, particularly among those with fewer coping motives. However, negative expectancies were related to more cannabis problems, particularly among those with higher coping motives. CONCLUSIONS: These results suggest it may be advisable to take coping motives into account when addressing expectancies among cannabis users. PMID- 27356274 TI - The 4(th) Great Wall Symposium, 2015. PMID- 27356275 TI - Constipation, fiber intake and non-compliance contribute to inadequate colonoscopy bowel preparation: a prospective cohort study. AB - OBJECTIVE: Adequate bowel preparation is important for colonoscopy. Currently available evidence on the determinants of poor bowel preparation is largely derived from studies in Western countries. We aimed to identify the risk factors for inadequate bowel preparation for colonoscopy in the Chinese population. METHODS: In this single-center study, patients admitted to the Outpatient Department between March 2013 and December 2015 and had indications for colonoscopy were prospectively enrolled. Questionnaires were administered to the patients. Their characteristics and procedure-related parameters such as procedure time were recorded. Bowel preparation was assessed using Boston bowel preparation scale score. RESULTS: A total of 409 patients with a mean age of 48.8 +/- 12.9 years were enrolled in the study, 60.9% of whom were men. On univariate analysis, poor educational level (P = 0.020), chronic constipation (P = 0.001), taking no physical exercise after medication (P < 0.001), a high-fiber diet during the 24-h period immediately preceding the colonoscopy (P < 0.001), incomplete intake of medication (P < 0.001), the passage of yellow or dark stools before colonoscopy (P < 0.001), waiting time (P = 0.001) and stool frequency after medication (P = 0.048) were significantly associated with inadequate bowel preparation. On multivariate analysis, chronic constipation [odds ratio (OR) 2.05, 95% confidence interval (CI) 1.31-3.23, P = 0.002], incomplete intake of the medication (OR 2.77, 95% CI 1.47-5.21, P = 0.002) and a high-fiber diet within 24 h before colonoscopy (OR 2.15, 95% CI 1.40-3.28, P < 0.001) were independent risk factors for inadequate bowel preparation. CONCLUSIONS: Chronic constipation, poor compliance with treatment and high-fiber diet were predictors of poor bowel preparation. Patients with these risk factors require more effective strategies for bowel preparation. PMID- 27356276 TI - DNA methylation in the NCAPH2/LMF2 promoter region is associated with hippocampal atrophy in Alzheimer's disease and amnesic mild cognitive impairment patients. AB - Several studies have noted an effect of DNA methylation on the pathogenesis of Alzheimer's disease (AD). We have already reported that DNA methylation levels in the NCAPH2/LMF2 promoter region can be a useful biomarker for the diagnosis of AD and amnesic mild cognitive impairment (aMCI). However, there is still uncertainty about the mechanism by which NCAPH2/LMF2 methylation affects the pathogenesis of AD and aMCI. In this study, we investigated relationships between NCAPH2/LMF2 methylation and other factors. AD (n=30) and aMCI (n=28) subjects were included in this study. NCAPH2/LMF2 methylation levels were measured by pyrosequencing. Correlations between methylation levels and other factors including age at onset, sex, duration of disease, education, mini-mental state examination (MMSE) and frontal assessment battery (FAB) scores, APOE genotype, degree of hippocampal atrophy, and total brain atrophy were measured. Degrees of hippocampal atrophy and total brain atrophy were measured by VSRAD (Voxel-Based Specific Regional Analysis System for Alzheimer's Disease). Regression analysis revealed that only hippocampal atrophy according to VSRAD is a significant dependent variable correlated with NCAPH2/LMF2 methylation levels. Our results suggest that DNA methylation in the NCAPH2/LMF2 promoter region is associated with hippocampal atrophy through apoptosis. PMID- 27356277 TI - Quantification of bone marrow fat content using iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL): reproducibility, site variation and correlation with age and menopause. AB - OBJECTIVE: To determine the reproducibility of the quantitative chemical shift based water-fat separation method with a multiecho gradient echo sequence [iteraterative decomposition of water and fat with echo asymmetry and least squares estimation quantitation sequence (IDEAL-IQ)] for assessing bone marrow fat fraction (FF); to evaluate variation of FF at different bone sites; and to investigate its association with age and menopause. METHODS: 31 consecutive females who underwent pelvic iterative decomposition of water and fat with echo asymmetry and least-squares estimation at 3-T MRI were included in this study. Quantitative FF using IDEAL-IQ of four bone sites were analyzed. The coefficients of variance (CV) on each site were evaluated repeatedly 10 times to assess the reproducibility. Correlations between FF and age were evaluated on each site, and the FFs between pre- and post-menopausal groups were compared. RESULTS: The CV in the quantification of marrow FF ranged from 0.69% to 1.70%. A statistically significant correlation was established between the FF and the age in lumbar vertebral body, ilium and intertrochanteric region of the femur (p < 0.001). The average FF of post-menopausal females was significantly higher than that of pre menopausal females in these sites (p < 0.05). In the greater trochanter of the femur, there was no significant correlation between FF and age. CONCLUSION: In vivo IDEAL-IQ would provide reliable quantification of bone marrow fat. ADVANCES IN KNOWLEDGE: IDEAL-IQ is simple to perform in a short time and may be practical for providing information on bone quality in clinical settings. PMID- 27356278 TI - Diamondoid Structure in a Metal-Organic Framework of Fe4 Single-Molecule Magnets. AB - A 3D metal-organic framework (MOF) having single-molecule magnet (SMM) linkers was prepared in crystalline form by using a tetrairon(III) complex functionalised with two divergent pyridyl groups, namely [Fe4 (pPy)2 (dpm)6 ] (1; H3 pPy=2 (hydroxymethyl)-2-(pyridin-4-yl)propane-1,3-diol, Hdpm=dipivaloylmethane). Reaction of 1 with silver(I) perchlorate afforded {[Fe4 (pPy)2 (dpm)6 ]2 Ag}ClO4 (2), which crystallises in a cubic face-centred lattice and exhibits two interlocked diamondoid networks. In 2, the SMMs act as linear ditopic synthons, and silver(I) ions as tetrahedral nodes coordinated by four pyridyl nitrogen atoms. The magnetic properties of 1 (S=5 and D~-0.4 cm(-1) in the ground spin state) are largely preserved in 2, which shows slow magnetic relaxation with an anisotropy barrier of Ueff /kB =11.46(10) K in zero field and 14.25(8) K in an applied field of 1 kOe. However, crystal symmetry triggers highly noncollinear magnetic anisotropy contributions oriented at 109.47 degrees from each other along the threefold axes of AgN4 tetrahedra, a unique scenario fully confirmed by a single-crystal cantilever torque magnetometry investigation. Magnetisation curves down to 0.03 K demonstrated the occurrence of a wide hysteresis loop when the magnetic field was swept along one of the four Ag-N bonds. By symmetry, the crystalline compound can then be persistently magnetised parallel or antiparallel to the four main diagonals of the unit cell, although the crystals have no overall second-order anisotropy. PMID- 27356279 TI - The Potential of Isotope Ratio Mass Spectrometry (IRMS) and Gas Chromatography IRMS Analysis of Triacetone Triperoxide in Forensic Explosives Investigations. AB - Studying links between triacetone triperoxide (TATP) samples from crime scenes and suspects can assist in criminal investigations. Isotope ratio mass spectrometry (IRMS) and gas chromatography (GC)-IRMS were used to measure the isotopic compositions of TATP and its precursors acetone and hydrogen peroxide. In total, 31 TATP samples were synthesized with different raw material combinations and reaction conditions. For carbon, a good differentiation and a linear relationship were observed for acetone-TATP combinations. The extent of negative (delta(13) C) fractionation depended on the reaction yield. Limited enrichment was observed for the hydrogen isotope (delta(2) H) values of the TATP samples probably due to a constant exchange of hydrogen atoms in aqueous solution. For oxygen (delta(18) O), the small isotopic range and excess of water in hydrogen peroxide resulted in poor differentiation. GC-IRMS and IRMS data were comparable except for one TATP sample prepared with high acid concentration demonstrating the potential of compound-specific isotope analysis. Carbon IRMS has practical use in forensic TATP investigations. PMID- 27356280 TI - Surface engineering of bismuth nanocrystals to counter dissolution. AB - Rapid dissolution of Bi Nanocrystals (NCs) in lysosomal conditions results in poor biocompatibility. We report that an in situ surface coating of Bi nanocrystals with Ganex(r) V216, a cosmetic dispersant, limits its dissolution under physiological conditions. These Bi Ganex (BiG) NCs are readily encapsulated in FDA approved polymer poly(dl-lactic-co-glycolic acid) (PLGA) by an oil-in water emulsion technique and also undergo facile SiO2 coating. BiG NCs in BiG@PLGA and BiG@SiO2 nanoparticles dissolve slowly under physiological conditions and exhibit excellent biocompatibility, as opposed to uncoated Bi NCs. Finally, these Bi nanoconstructs are shown to be strong CT CAs, even at relatively low Bi concentrations. PMID- 27356281 TI - Effects of fast walking on tibiofemoral bone water content in middle-aged adults. AB - BACKGROUND: Although it is believed that genu varum increases loading on the medial knee during locomotion, the acute effect of increased loading on bone stress has not been determined. This study aimed to examine the effects of locomotion and lower extremity alignment on bone water content in middle-aged adults without knee osteoarthritis. METHODS: Five males and 5 females participated. Lower extremity alignment was defined as the angle between the midpoint of the anterior mid-thigh and the midpoint of the patellar tendon using the center of the patella as the fulcrum. A chemical-shift-encoded water-fat magnetic resonance imaging protocol was used to assess bone water content before and after a 30-minute fast walking session. Bone stress response was determined by quantifying water content within the weight-bearing regions of the medial and lateral compartments of the tibiofemoral joint. Paired t-tests were used to compare bone water content before and after fast walking. Pearson correlation coefficients were used to determine the associations between lower extremity alignment and changes in water content post-walking. FINDINGS: The paired t-tests revealed no changes in water content after fast walking within medial and lateral femur/tibia (P>0.05). Pearson correlation analyses revealed a significant moderate correlation between increased bone water content of the medial femur and increased varus alignment (R=0.688, P=0.028). INTERPRETATION: Although there was no significant change in bone water content following locomotion, knee varus was associated with signs of bone stress in the medial femur. PMID- 27356282 TI - Co(II) PCP Pincer Complexes as Catalysts for the Alkylation of Aromatic Amines with Primary Alcohols. AB - Efficient alkylations of amines by alcohols catalyzed by well-defined Co(II) complexes are described that are stabilized by a PCP ligand (N,N' bis(diisopropylphosphino)-N,N'-dimethyl-1,3-diaminobenzene) based on the 1,3 diaminobenzene scaffold. This reaction is an environmentally benign process implementing inexpensive, earth-abundant nonprecious metal catalysts and is based on the acceptorless alcohol dehydrogenation concept. A range of primary alcohols and aromatic amines were efficiently converted into mono-N-alkylated amines in good to excellent isolated yields. PMID- 27356283 TI - A Mixed-Valent Uranium Phosphonate Framework Containing U(IV) , U(V) , and U(VI). AB - It is shown that U(V) O2 (+) ions can reside at U(VI) O2 (2+) lattice sites during mild reduction and crystallization process under solvothermal conditions, yielding a complicated and rare mixed-valent uranium phosphonate compound that simultaneously contains U(IV) , U(V) , and U(VI) . The presence of uranium with three oxidation states was confirmed by various characterization techniques, including X-ray crystallography, X-ray photoelectron, electron paramagnetic resonance, FTIR, UV/Vis-NIR absorption, and synchrotron radiation X-ray absorption spectroscopy, and magnetism measurements. PMID- 27356284 TI - Long-term outcome of surgical resection for intraductal papillary neoplasm of the bile duct. AB - BACKGROUND AND AIMS: Intraductal papillary neoplasm of the bile duct (IPNB) is a specific type of bile duct tumor. Studies about the surgical outcomes for IPNB are few; therefore, we investigated the survival of patients who underwent curative surgical resection of IPNB. METHODS: We retrospectively reviewed the medical and pathological records of 148 IPNB patients who underwent curative intent hepatic resection between January 2005 and December 2011, to examine the prognosis of IPNB. All demographic and operative parameters were analyzed the effect on survival of patients. RESULTS: The median survival of IPNB patients was 1326 days with a respective 1, 3, and 5 year overall survival of 83.6% (95%CI: 76.5-88.7), 64.4% (95%CI: 56.0-71.6), and 47% (95%CI: 38.4-55.7). The level of invasiveness of IPNB predicted survival very well. For malignant IPNB, univariate analysis showed that serum CA19-9 level, lymph node metastasis, and completeness of resection were significant prognostic factors. Lymph node metastasis and completeness of resection were found in multivariate analysis to be significantly related to survival of the patients. CONCLUSIONS: The level of invasiveness and lymph node status were found to be associated with patient survival, as was adequacy of surgery. We recommend R0 resection be attempted for patients with IPNB. PMID- 27356285 TI - Genetic variants determining survival and fertility in an adverse African environment: a population-based large-scale candidate gene association study. AB - Human survival probability and fertility decline strongly with age. These life history traits have been shaped by evolution. However, research has failed to uncover a consistent genetic determination of variation in survival and fertility. As an explanation, such genetic determinants have been selected in adverse environments, in which humans have lived during most of their history, but are almost exclusively studied in populations in modern affluent environments. Here, we present a large-scale candidate gene association study in a rural African population living in an adverse environment. In 4387 individuals, we studied 4052 SNPs in 148 genes that have previously been identified as possible determinants of survival or fertility in animals or humans. We studied their associations with survival comparing newborns, middle-age adults, and old individuals. In women, we assessed their associations with reported and observed numbers of children. We found no statistically significant associations of these SNPs with survival between the three age groups nor with women's reported and observed fertility. Population stratification was unlikely to explain these results. Apart from a lack of power, we hypothesise that genetic heterogeneity of complex phenotypes and gene-environment interactions prevent the identification of genetic variants explaining variation in survival and fertility in humans. PMID- 27356299 TI - Cholesterol crystals activate Syk and PI3 kinase in human macrophages and dendritic cells. AB - BACKGROUND AND AIMS: Cholesterol crystals are a key component of atherosclerotic lesions where they promote pro-inflammatory cytokine production and plaque destabilization. Antagonists of inflammatory mediators and agents that dissolve or prevent the formation of cholesterol crystals are being explored as potential therapeutics for atherothrombosis. We sought to identify signalling molecules activated following exposure of immune cells to cholesterol crystals with the view to identifying novel therapeutic targets. METHODS: Human macrophages and dendritic cells (DC) were exposed to cholesterol crystals and activation of signalling molecules was assessed by immunoblotting. The role of Syk and PI3K in crystal-induced interleukin (IL)-1 production was determined by ELISA using specific kinase inhibitors. Real-time PCR was employed to examine the role of Syk/PI3K in cholesterol crystal-induced expression of S100 proteins and MMPs. RESULTS: Exposure of human macrophages and DC to cholesterol crystals induced robust activation of Syk and PI3K within 2-5 min. Pharmacological inhibition of Syk/PI3K reduced crystal-induced IL-1alpha/beta production by approximately 80%. Activation of the downstream MAP kinases, MEK and ERK, was suppressed following inhibition of Syk and PI3K. Finally, inhibition of both Syk and PI3K significantly reduced cholesterol crystal-induced S100A8 and MMP1 gene expression by >70% while inhibition of PI3K also reduced S100A12 expression. CONCLUSION: Cholesterol crystals activate specific cell signalling pathways which drive the production of inflammatory cytokines and degradative enzymes known to contribute to disease initiation and progression. These molecular events are dependent on activation of Syk and PI3K, hence, they represent potential therapeutic targets for the treatment of cholesterol crystal-related pathologies. PMID- 27356300 TI - OFF-SITE SMARTPHONE VS. STANDARD WORKSTATION IN THE RADIOGRAPHIC DIAGNOSIS OF SMALL INTESTINAL MECHANICAL OBSTRUCTION IN DOGS AND CATS. AB - Off-site consultations by board-certified veterinary radiologists benefit residents and emergency clinicians by providing immediate feedback and potentially improving patient outcome. Smartphone devices and compressed images transmitted by email or text greatly facilitate availability of these off-site consultations. Criticism of a smartphone interface for off-site consultation is mostly directed at image degradation relative to the standard radiographic viewing room and monitors. The purpose of this retrospective, cross-sectional, methods comparison study was to compare the accuracy of abdominal radiographs in two imaging interfaces (Joint Photographic Experts Group, off-site, smartphone vs. Digital Imaging and Communications in Medicine, on-site, standard workstation) for the diagnosis of small intestinal mechanical obstruction in vomiting dogs and cats. Two board-certified radiologists graded randomized abdominal radiographs using a five-point Likert scale for the presence of mechanical obstruction in 100 dogs or cats presenting for vomiting. The area under the receiver operator characteristic curves for both imaging interfaces was high. The accuracy of the smartphone and traditional workstation was not statistically significantly different for either reviewer (P = 0.384 and P = 0.536). Correlation coefficients were 0.821 and 0.705 for each reviewer when the same radiographic study was viewed in different formats. Accuracy differences between radiologists were potentially related to years of experience. We conclude that off-site expert consultation with a smartphone provides an acceptable interface for accurate diagnosis of small intestinal mechanical obstruction in dogs and cat. PMID- 27356301 TI - Controlling Ethylene Hydrogenation Reactivity on Pt13 Clusters by Varying the Stoichiometry of the Amorphous Silica Support. AB - Ethylene hydrogenation was investigated on size-selected Pt13 clusters supported on three amorphous silica (a-SiO2 ) thin films with different stoichiometries. Activity measurements of the reaction at 300 K revealed that on a silicon-rich and a stoichiometric film, Pt13 exhibits a similar activity to that of Pt(111), in line with the known structure insensitivity of the reaction. On an oxygen-rich film, a threefold increased rate was measured. Pulsing ethylene at 400 K, then measuring the activity at 300 K, resulted in complete loss of activity on the silicon-rich surface compared to only marginal losses on the other surfaces. The measured reactivity trends correlate with charging characteristics of a Pt13 cluster on the SiO2 films, predicted through first-principle calculations. The results reveal that the stoichiometry-dependent charging by the support can be used to tune the selectivity of reaction pathways during a catalytic hydrogenation reaction. PMID- 27356302 TI - Oral azithromycin and blepharitis: symptoms and signs improve, so where are the publications? PMID- 27356303 TI - Intraarticular slow-release triamcinolone acetate reduces allodynia in an experimental mouse knee osteoarthritis model. AB - Intraarticular steroid injection has been the mainstay of short-term treatment of knee osteoarthritis (OA) pain. However, the duration of therapeutic effect from a single injection is not as long as desired. In this study we use a viscous formulation of triamcinolone acetate (TCA) in hyaluronic acid to prolong the anti allodynia effect of that steroid. OA was induced in mice by a partial medial meniscectomy. Over time the animals' developed a mechanical allodynia in the injected leg. Mice were then given a single intraarticular injection of TCA in a short-acting DMSO formulation, or a standard commercial suspension, or the drug formulated in 5% hyaluronic acid for slow-release. Control injections in OA mice were PBS or 5% hyaluronic acid vehicle. Mechanical allodynia was then monitored over the therapeutic period. Organotypic spinal cord slices and DRG culture were performed to assess whether TCA attenuates expressions of pain mediators induced by interleukin 1beta. TCA 40MUg in a fast-releasing DMSO formulation produced relief from mechanical allodynia for a few days compared to PBS control injections (P=0.007). Similarly, the commercial suspension of TCA 40MUg also produced relief from mechanical allodynia for a few days compared to PBS control injections (P=0.001). However, TCA 100MUg in 5% hyaluronic acid produced relief from mechanical allodynia for at least 28days compared to PBS control or 5% hyaluronic acid vehicle injections (P=0.0005). Furthermore, TCA significantly suppressed expression of pain mediators induced by interleukin 1beta in spinal cord and DRG organotypic culture. Intraarticular TCA in a sustained release formulation of viscous 5% hyaluronic acid will produce a long-term attenuation of mechanical allodynia in the OA knees of mice. PMID- 27356304 TI - Impact of CYP2C19 gene polymorphism on warfarin maintenance doses in patients with non-valvular atrial fibrillation. AB - BACKGROUND: Pharmacogenetics has provided compelling evidence towards the influence of gene polymorphisms on warfarin therapies. This study aimed to determine the impact of CYP2C19 gene polymorphism on warfarin maintenance doses in patients with non-valvular atrial fibrillation for the progress in overcoming obstacles facing warfarin pharmacogenetics. METHODS: In this study, we utilized polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to investigate the distribution of CYP2C19*2 and *3 gene polymorphism in patients with NVAF. In order to exclude the interference of basic indexes, we compared the association between different genotypes and warfarin maintenance doses. And the comparisons among extensive metabolizer, intermediate metabolizer and poor metabolizer were performed. RESULTS: CYP2C19 mutation accounted for 88.07% of in total NVAF patients, which was 7.38 times of CYP2C19*1/*1 (11.93%). No significant association was observed between different genotypes and basic indexes. The warfarin maintenance dose of patients with CYP2C19*1/*1 was significantly higher than those with other five genotypes (all P<0.05). Besides, the warfarin maintenance doses of patients with CYP2C19*1/*2 and *1/*3 were remarkably higher than those with *2/*2 and *2/*3 (P<0.05). The warfarin maintenance doses of patients with extensive metabolizer were dramatically higher than those with intermediate metabolizer and poor metabolizer (both P<0.05), and also the patients with intermediate metabolizer had higher warfarin maintenance doses than those with poor metabolizer (P<0.05). CONCLUSION: CYP2C19 gene polymorphism can affect maintenance dose of warfarin, with the amount of warfarin dose ranked among different genotypes as follow: CYP2C19*2/*2, CYP2C19*2/*3 and CYP2C19*3/*3100 tropical and subtropical countries. Urbanization, human population growth and expanded global travel have resulted in an increase in the incidence of dengue worldwide. International travellers to areas with endemic dengue are at risk of contracting dengue and US Peace Corps Volunteers are one specific group of long-term travellers who are exposed to environments where dengue can be contracted. METHODS: Cases of dengue among Peace Corps Volunteers, defined as clinically apparent infections with laboratory confirmation by a positive NS1 antigen test, demonstration of IgM antibodies or by a 4-fold increase in IgG antibodies, between 1 January 2000 and 31 December 2014, reported to the Peace Corps' Epidemiologic Surveillance System were analyzed. RESULTS: Overall there were 1448 cases of dengue reported among Volunteers, with an incidence rate of 1.12 cases per 1000 Volunteer-months (95% CI 1.06-1.17). The highest rate of dengue among Volunteers was reported in the Caribbean region, with a rate of 5.51 cases per 1000 Volunteer-months (95% CI 4.97-6.10), followed by the East Asia/South Asia region (3.34, 95% CI 2.96-3.75) and Central America (2.55, 95% CI 2.32-2.79). The rate of dengue peaked in 2007, 2010 and 2013. Each peak year was followed by a trough year. CONCLUSIONS: Globally, there appears to be a 3-year cyclical pattern of dengue incidence among Volunteers, with differences by region. Dengue continues to be a priority health issue for travellers to endemic areas, and enhanced surveillance of dengue among international travellers may result in improved patient education and prevention efforts. PMID- 27356309 TI - Louse-borne relapsing fever in a refugee from Somalia arriving in Belgium. AB - We report a case of louse-borne relapsing fever (LBRF) in a refugee from Somalia who had arrived in Belgium a few days earlier. He complained of myalgia and secondarily presented fever. Blood smears revealed spirochetes later identified as Borrelia recurrentis. LBRF should be considered in countries hosting refugees, particularly those who transit through endemic regions. PMID- 27356310 TI - AHRQ Analysis: Hospital-Acquired Conditions Reduced by 17% From 2010 to 2013. PMID- 27356311 TI - [Not Available]. PMID- 27356312 TI - New Curriculum Gives DMD Students Earlier Clinical Experience. PMID- 27356313 TI - Combating the Opioid Crisis Through Education. NIH funds educational modules in pain management. PMID- 27356314 TI - Dr. Donald B. Giddon. Champion of the Oral Physician. PMID- 27356315 TI - Checking Your Teeth and Your Vitals. Collaboration with Northeastern University School of Nursing brings primary care services into a dental care practice. PMID- 27356316 TI - HSDM Student Entrepreneur Is a Finalist for the President's Challenge. PMID- 27356317 TI - Gordon and Ruth Macdonald Establish a $2 Million Planned Gift to HSDM. PMID- 27356318 TI - Think global, act local. PMID- 27356319 TI - Clean, green, and financially lean. PMID- 27356320 TI - Nursing and Midwifery Consultative Forums--GETTING BACK TO BASICS. PMID- 27356322 TI - Easy does it--transitioning to digital. PMID- 27356321 TI - Connecting ruraL and remote services. PMID- 27356323 TI - Domestic violence leave introduced for public sector. PMID- 27356324 TI - Addressing workplace bullying. PMID- 27356325 TI - Setting the standard for consultation. PMID- 27356326 TI - Making 2016 the year to get serious on aged care staffing. PMID- 27356327 TI - The Clinical Services Capability Framework. PMID- 27356328 TI - Paid parental leave--they still don't get it. PMID- 27356329 TI - Welcoming the future of nursing and midwifery. PMID- 27356331 TI - Natural justice in the public sector. PMID- 27356330 TI - Making universal health care an election priority. PMID- 27356332 TI - Reflective exercise: Natural justice in the public sector. PMID- 27356333 TI - Making nurses and midwives part of the decision-making process. PMID- 27356334 TI - Midwives empowered through domestic violence training. PMID- 27356336 TI - QNU joins taskkforce on violence against nurses and midwives. PMID- 27356335 TI - A lot can happen in three years.... PMID- 27356337 TI - Beautiful Surfaces. Style and Substance in Florentius Schuyl's Illustrations for Descartes' Treatise on Man. AB - The assumption that the Cartesian bete-machine is the invention of Rene Descartes (1596-1650) is rarely contested. Close examination of Descartes' texts proves that this is a concept founded not on the basis of his own writings, but a subsequent critical interpretation, which developed and began to dominate his work after his death. Descartes' Treatise on Man, published posthumously in two rival editions, Florentius Schuyl's Latin translation De Homine (1662), and Claude Clerselier's Traite de l'homme, has proved particularly problematic. The surviving manuscript copies of the Treatise on Man left no illustrations, leaving both editors the daunting task of producing a set of images to accompany and clarify the fragmented text. In this intriguing case, the images can be seen to have spoken louder than the text which they illustrated. This paper assesses Schuyl's choice to represent Descartes' Man in a highly stylized manner, without superimposing Clerselier's intentions onto De Homine. PMID- 27356338 TI - The Encounter of the Emblematic Tradition with Optics. The Anamorphic Elephant of Simon Vouet. AB - In his excellent work Anamorphoses ou perspectives curieuses (1955), Baltrusaitis concluded the chapter on catoptric anamorphosis with an allusion to the small engraving by Hans Troschel (1585-1628) after Simon Vouet's drawing Eight satyrs observing an elephant reflected on a cylinder, the first known representation of a cylindrical anamorphosis made in Europe. This paper explores the Baroque intellectual and artistic context in which Vouet made his drawing, attempting to answer two central sets of questions. Firstly, why did Vouet make this image? For what purpose did he ideate such a curious image? Was it commissioned or did Vouet intend to offer it to someone? And if so, to whom? A reconstruction of this story leads me to conclude that the cylindrical anamorphosis was conceived as an emblem for Prince Maurice of Savoy. Secondly, how did what was originally the project for a sophisticated emblem give rise in Paris, after the return of Vouet from Italy in 1627, to the geometrical study of catoptrical anamorphosis? Through the study of this case, I hope to show that in early modern science the emblematic tradition was not only linked to natural history, but that insofar as it was a central feature of Baroque culture, it seeped into other branches of scientific inquiry, in this case the development of catoptrical anamorphosis. Vouet's image is also a good example of how the visual and artistic poetics of the baroque were closely linked--to the point of being inseparable--with the scientific developments of the period. PMID- 27356339 TI - The "Abyssal Society". Francois-Alphonse Forel and the Case of Deep Fauna in Late 19th Century. AB - Ichthyological investigations and technological advancements, such as the laying of submarine telegraph cables, promoted new dredging methods in the second half of the 19th century. In contrast to the idea of a lifeless deep ocean (Edward Forbes' azoic hypothesis), the discovery of deep water fauna and the challenge of defining its systematics opened up new theoretical perspectives. In this frame, which was already marked by the impact of Darwin's theory, naturalistic surveys in freshwater environments in western Switzerland intertwined with those of oceanographic expeditions. The study of the fauna in the depths of subalpine lakes by the Swiss savant Francois-Alphonse Forel was one of the most striking examples of this turning point, because the relatively recently evolution of its freshwater fauna allowed him to investigate: (a) the role of isolation, (b) the progressive differentiation of species from a common ancestor, and (c) the constitution of a species-specific category in form transition, from a genealogical viewpoint to an ecological one. PMID- 27356340 TI - Marble Busts and Fish Fossils. The Catalog of the Museum of naturalia and artificialia at the University of Padua (1797). AB - The historical catalogs of the museum collections contain a wealth of information for historians seeking to reconstruct their contents, how they were displayed and the ways in which they were used. This paper will present the complete transcription of a draft catalog that was prepared in 1797 for the Museum of Natural History and Antiquities of the University of Padua. Conserved in the university's Museum of Geology and Paleontology, the catalog was the first to be compiled of the museum, which was established in 1733 thanks to the donation by Antonio Vallisneri Jr. of his father Antonio Vallisneri Sr.'s collection of antiquities and natural history. The catalog was compiled by the custodian of the museum, the herbalist and amateur naturalist Bartolomeo Fabris. It is of great interest because it provides a record of the number and nature of the pieces conserved in the museum at a time when natural history and archeology collections were still undivided. It also provides indications as to how such collections were arranged for display in the public halls of a university at the end of the eighteenth century. Based on this catalog, with additional information drawn from other manuscript and published sources and museum catalogs from the 1830s conserved in various institutes at the University of Padua, it is possible to reconstruct the contents and layout of a significant late 18th-century natural history collection. PMID- 27356341 TI - [Foreword]. PMID- 27356342 TI - [BIOETHICS: THE ABILITY TO UNDERSTAND MAN, THE POWER TO STANDARDIZE THE FACTS]. AB - Bioethics is both theoria and praxis. It procceds by tactics which accompany dynamics of science and mobility of ethics, concerning values specific to spaces, periods and cultures. In this perspective, bioethics, with its normative requirements, is situated beyond gouvernmental policy. The rules related to bioethics contains meta-values. Value imposed to a fact by legal rules is an existential meta-value, because there are already values that surround the nature of this fact the the morality this nature contains. PMID- 27356344 TI - [SUMING UP]. AB - The conference showed that bioethics currently represents such a vast field that it no longer has any temporal, spatial or material boundaries. It gives rise to different approaches, either global or sectoral, none of which is sufficient to resolve the problems raised as these remain highly sensitive both from a political and a legal standpoint. The issue is now a matter for the national legislator. PMID- 27356343 TI - [THE FRENCH BIOETHICS LAWS HAVE 20 YEARS!]. AB - Technological and scientific progress in the field of biology and genetics raise both legal and ethical questions treated by the laws of 1994, modified in 2004 and in 2011. But each day, new discoveries lead national and European judges, to make praetorian work, in waiting for updated texts. More than ever the discoveries require a framing, as well it is true that "science without conscience is only ruin of the heart". PMID- 27356345 TI - [THE WISHED ACCESS TO THE ORIGINS: WHICH ACCESS?]. AB - The anonymity of the donor of gametes is a principle required by the bioethics laws and confirmed by the judges, within the framework of medical help to procreation. It is disputed by the children born after a donation. The rule of the secrecy knows however already particular installations, it is consequently relevant to see to which extent a parallel could be considered for the newborns from such a donation. This principle of anonymity is not absolute and can be opposite to the person in identity search, several legal bases can be exploited for this purpose. PMID- 27356346 TI - [CIRCUMCISION AND EXCISION: TOWARDS A NON-LAW OF BIOETHICS?]. AB - This article defines the practices of circumcision and excision, and studies their foundations. Then, it considers some of the conflicts (of rights, laws and cultures) inherent to these practices. Finally, it suggests that the solution to these conflicts may not lie in the law, but in a non-law of bioethics. PMID- 27356347 TI - [TRANSSEXUALISM]. AB - Transsexualism is characterised by a person's strong wish to belong to the opposite sex and the obsessional desire to align their assigned sex to that with which they truly identify; it is a firm belief. For a long time, the chromosome analysis criterion led to all requests for legal identity change to be refused in civil registers. Nevertheless, following a judgement pronounced by the ECHR in 1992 and vehement trans-identity demands, the French state was forced to relax the conditions allowing social change to be undertaken. Under the influence of European law and other international provisions, legislative action was opened to debate. The bioethical laws of 29 July 1994, 6 August 2004 and 7 July 2011 did not, however, provide a legal framework for transsexualism. The question remains a matter for jurisprudence through the court of cassation. This case-law approach -a vector of legal insecurity and inequality--places transgender people in a highly-precarious social situation. PMID- 27356348 TI - [MEDICALLY ASSISTED PROCREATION AND HOMOSEXUAL COUPLES]. AB - With the legalization of the same-sex marriage in France, the medically assisted procreation has returned to the heart of discussions relating to the family. So far, the French legislator has strictly limited access to such medical techniques to sterile heterosexual couples only. Thus, the possibility of giving birth is denied to people who are in a "social" sterility position, such as singles or gays. Is such decision still ethically and socially acceptable? Should the French Legislator on the contrary widen access to the MPA? The debate is revived and raises important ans interesting questions that this article intends to address. PMID- 27356349 TI - [PRESERVING FERTILITY AND FUTURE DEATH]. AB - The fertility preservation when it is threatened is a right enshrined in the french law on bioethics. It is most often performed before gonadotoxic treatments for cancers with a long survival. When the patient has a limited life expectancy, is the preservation of fertility lawful? The authors present the arguments for and against the preservation of fertility in this particular situation and give driving they adopt in their team. PMID- 27356350 TI - [POST MORTEM PATERNITY]. AB - Post mortem paternity, namely the procreation after the death of the man whom is part of the couple, is one of the questions which raised the most hesitations since the first bioethics laws of 1994. The National Assembly, encouraged by several opinions of the CCNE (National advisory committee of ethics) had let itself convince that the transfer had, at least, to be authorized in utero embryos preserved at the regard of which no one could not claim to have rights equal or higher than those of the woman concerned. However, the Senate always ended up obtaining the maintenance of an absolute prohibition of posthumous procreation (starting) from the spermatozoids or frozen embryos. This indifference with the cruelty of the application of the law to the women plunged into mourning--based on a paradoxical appreciation of the interest of the child not to be born orphan, and on a not very glorious taking into account of the interest of the Body of notaries not to change its practices--is particularly debatable. One can, nevertheless, try to understand it according to the obsession of the legalization of surrogate motherhood by application of the principle of nondiscrimination which could justify the requests of the men who, thanks to a surrogate mother, would wish to become fathers starting from gametes or embryos taken or created before the death of their wife or partner. PMID- 27356351 TI - [COMPARATIVE STUDY ON THE SECRET OF THE DONOR'S IDENTITY OF DONATED GAMETES]. AB - French law lies down a principle of anonymity of donated gametes. This principle is ignored by English law. Moreover, English law has established, few years ago, the contrary principle: the one of transparency of the donor's identity. This study of English law reports this evolution and its consequences. PMID- 27356352 TI - [SURROGACY: TOWARDS LEGALISATION?]. AB - Surrogacy today is under an absolute legal ban by means of article 16-7 of the Civil Code, resulting from the law of 29 July 1994 and which the revisions of 2006 and 2011 have in no way modified. The Court of Appeal until 2014 ensured the impact of this text by refusing to transcribe on the national registers the birth certificates drawn up abroad of children born thanks to a protocol of surrogacy. While a circular of 2013, recently validated by the Council of State, allows certificates of French nationality to be delivered to these children, France has been condemned by the European Court of Human Rights for infringement of their privacy. These latest developments, which will undoubtedly have consequences for the Appeal Court's position, provide France with an opportunity to re-open a debate which up to now, has had no results. PMID- 27356353 TI - [THE RIGHT TO A CHROMOSOMICALLY PERFECT CHILD]. AB - After defining the terms "perfect," "chromosomically" and "right" we discuss on the scope and terms of the right to a chromosomically perfect child. This right is it addressed to a target population or to the general population? What are the exams available and the means of diagnosis or screening to be implemented? The practice of genetic testing being highly controlled, some rules are then discussed. All over the paper, a reflection is proposed on what is allowed versus what is possible with reference to ethics. PMID- 27356354 TI - [RESEARCHES ON EMBRYO: THE RISKS OF EUGENIC DRIFTS AND LIVING MATTER UNDER PATENT]. AB - As a result of scientific progress, embryo, once classified as part of the maternal body, gained recognition in particular with medically assisted reproduction. It became a genuine topic of study, from being analyzed in its development to its characteristics of being a reserchers's object of desire due to its multiple possibilities of reserch and study. Despite belonging to the human species, and even though they are not completely classified as objects, supernumerary embryos, out of parental projects, were gradually reified in order to become the object of all genetic engineering fantasies, especially the quest of the perfect child, free of diseases and anomalies. Notwithstanding all the precautions taken by the legislator and the European institutions, future drifts concerning the enlargement of prenatal diagnostics and of living matter under patent possibilities are to be feared. PMID- 27356355 TI - [THE LEGAL STATUS OF ELEMENTS AND PRODUCTS OF THE HUMAN BODY: OBJECT OR SUBJECT OF LAW?]. AB - The 2004 Act on bioethics has amended the 1994 Act regarding the donation and the use of elements and products of the human body, medically assisted procreation and prenatal diagnosis. The very purpose of these laws led the legislature not to attempt the summa divisio order distinguishing the object to the person. The analysis of bioethical laws reveals the consecration of the non-commercialization of the human body at the expense of its unavailability. Bioethical laws appear to be catalysts of biological scientific advances releasing the status of the components and the products of the human body while framing it. By limiting scientific opportunities, they prevent human beings from trying to play the sorcerer's apprentice. PMID- 27356356 TI - [THE USE AND STORAGE OF STEM CELLS AND CORD BLOOD: FRENCH AND ENGLISH LAW COMPARATIVE APPROACH]. AB - Becoming parents is one of the greatest wishes of a lot of couples. When their dreams come true, prior to the birth of the child, parents have to face several points: the choice of the name, place of delivery, breast or bottle feeding, etc. Recently, they have to face the issues of cord blood stem cells. Researchers and cord blood banks are also interested in those cells. In many countries a lot of advertising is made around umbilical cord blood stem cells. In France as in England, the use and preservation of cord blood are regulated by the legislators without necessarily having the same approach. The objective of this paper is to present English and French law approaches' on cord blood stem cells. PMID- 27356357 TI - [SELECTED ETHICAL ISSUES IN ONCOGENETICS]. AB - Oncogenetics is the medical care of families with hereditary cancer risk. Bioethics laws strictly control this activity. Taking into account the medical benefit and lives saved through oncogenetics when a constitutional mutation in hereditary cancer risk gene is found, the law requires that information is disseminated to the relatives. If the consultant cannot or will not provide this information, this is the geneticist who will contact the family. This is an unprecedented situation where the doctor encourages medical advices not requested by patients. The Clermont experience is shown on the application of the law and its practical difficulties. Currently the technology of molecular genetic diagnosis is changing rapidly and allows new diagnostics whether at the level of cancerous tumors or in the genome with the perspective that everyone can soon have the sequence of the entire genome with the interpretation of personal risk of cancer diseases or other kinds. It is necessary to better anticipate emerging ethical issues already raised by the first medical practices of these technologies. PMID- 27356358 TI - [EUTHANASIA AND ASSISTED SUICIDE]. AB - Euthanasia and assisted suicide are not part of French laws of bioethics and lack, for the time being, definition and normative framework other than their criminal prosecution. To transform them into a right, these concepts certainly call for an ethical and legal debate. This paper aims to question the ideas to be considered, the conceptual bases and normative tools that may be useful to the discussion. PMID- 27356359 TI - THE USE OF THE NOTION OF HUMANITY IN FRENCH LAW. AB - The lawyers little informed about the specificities of the French law often wonder about the use of the concept of dignity and about that of humanity who accompanies hit. This article makes a point on the sense give to this "humanity" which "is at one" with the subject of right. PMID- 27356360 TI - [Not Available]. PMID- 27356361 TI - [Not Available]. PMID- 27356362 TI - [Not Available]. PMID- 27356363 TI - [Not Available]. PMID- 27356365 TI - [Not Available]. PMID- 27356364 TI - [Not Available]. PMID- 27356366 TI - [Not Available]. AB - Non alcoholic fatty liver diseases (NAFLD) is a clinicopathological entity that encompasses simple steatosis, necroinflammation known as non alcoholic steatohepatitis (NASH) with or without fibrosis. It is strongly associated with the metabolic syndrome. NAFLD is by far the most common cause of liver disease. Key issues in the diagnosis of patients with NAFLD are the differentiation of NASH from simple steatosis and the degree of liver fibrosis. Patients with NASH are at greatest risk of developing complications of chronic liver disease, such as hepatocellular carcinoma even in the absence of cirrhosis. Liver biopsy, which is the gold standard diagnostic method, cannot be proposedfor all patients, given the risk of this procedure and the prevalence of NAFLD. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. Knowledge about the interaction between the intestinal microbiota in obesity has rapidly increased in the past few years. Several lines of evidence suggest a role for the gut microbiota in the pathogenesis of NAFLD. Dysbiosis, i.e. imbalance of the intestinal microbiome, may have a role in the progression of NAFLD. At the present time, there are limited treatment options wich include lifestyle modification to lose weight, treatment of the disorders included in the metabolic syndrome and different therapeutic agents. However results are disappointing concerning liver inflammation and fibrosis. Manipulating the gut microbiota may represent a new strategy for patients with NAFLD. PMID- 27356367 TI - [Metabolic syndrome, non alcoholic hepatic steatopathy and hepatocellular carcinoma: so dangerous liaisons]. AB - Obesity and the metabolic syndrome are fast-growing epidemics associated with an increased risk for many types of cancer. In the liver, inflammatory and angiogenic changes due to insulin resistance and fatty liver disease are associated with an increased incidence of liver cancer. Regardless of underlying liver disease, cirrhosis remains the most important risk factor for hepatocellular carcinoma (HCC) although cases of HCC arising without cirrhosis do not exclude the possibility of a direct carcinogenesis secondary to non-alcoholic fatty liver disease. Moreover, metabolic syndrome and its different features may also increase the risk of HCC in the setting of chronic liver diseases of other causes, such as viral hepatitis or alcohol abuse. Taking into account all these data, it is necessary to better determine the risk of developing HCC in patients with metabolic syndrome to improve the screening guidelines and develop prophylactic treatments in this setting. PMID- 27356368 TI - [Not Available]. PMID- 27356369 TI - [Intestinal microbiota]. AB - The human body normally lives in symbiosis with a considerable microscopic environment present on all interfaces with the external environment; it hosts ten times more microbes (microbiota) that it has somatic or germ cells, representing a gene diversity (microbiome) 100-150 times higher than the human genome. These germs are located mainly in the gut, where they represent a mass of about one kilogram. The primary colonization of the gastrointestinal tract depends on the delivery route, the bacterial flora rewarding then depending on the environment, food hygiene, medical treatments. The intestinal microbiota plays an important role in the maturation of the immune system and in different physiological functions: digestion of polysaccharides, glycosaminoglycans and glycoproteins, vitamins biosynthesis, bile salt metabolism of some amino acids and xenobiotics. Quantitative and qualitative changes in the microbiota are observed in a wide range of diseases: obesity, colorectal cancer, liver cancer, inflammatory bowel disease, autoimmune diseases, allergies... pharmacobiotics aim to modify the intestinal microbiota in a therapeutic goal and this by various means: prebiotics, probiotics, antibiotics or fecal transplants. Intestinal flora also plays a direct role in the metabolism of certain drugs and the microbiota should be considered as a predictive parameter of response to some chemotherapies. PMID- 27356370 TI - [Health and housing]. AB - The report recalled the determinants of air quality in buildings and the dysfunctions which are most commonly found in buildings. They have their roots in economic, sociologic, demographic and technologic changes which occurred in last decades. Then, the authors stated what should be the health issues at each step of the life of a building, namely planning by the architect, construction, maintenance, rehabilitation and, in some instances, control by health authorities. These shortcomings back up the advices to introduce health issues in the management of buildings, to include basic knowledge on housing in school programs and health in the training of professionals, lastly to improve and speed up legal procedures to better control unhealthy housing. PMID- 27356371 TI - [Study on Rapid Micropropagation in Vitro Technique of Guangfeng Medicinal Yam (Dioscorea opposita) Plantlets]. AB - OBJECTIVE: In order to provide methodology reference for virus-free and germplasm conservation of Guangfeng medicinal yam (Dioscorea opposita) plantlets, rapid micropropagation in vitro technique of Guangfeng medicinal yam plantlets was studied. METHODS: Using the method of plant tissue culture, single factor test and flow-cytometry, the basic procedure of Guangfeng medicinal yam tissue culture was established and the DNA content of Guangfeng medicinal yam plantlets and its potted seedlings was detected. RESULTS: The best disinfection procedure of stems with a bud of Guangfeng medicinal yam was washed with sterile water for three times after sterilized with 70% alcohol for 20 - 30 s and then washed with sterile water for three times again after sterilized with 0.1% mercuric chloride for 10 - 12 min; The best explants of stems with a bud of Guangfeng medicinal yam was slightly woody and more mature stems witha bud; The best proliferation culture medium of stems with a bud of Guangfeng medicinal yam was MS + 6-BA 2.0 mg/L + NAA 0.1 mg/L; The best rooting culture medium of stems with a bud of Guangfeng medicinal yam was MS + NAA 0.5 mg/L; The best culture method of Guangfeng medicinal yam plantlets was liquid culture; The best transplanting matrix of Guangfeng medicinal yam plantlets was the mixture of paddy clay and fine sand (1: 2) or the mixture of perlite and vermiculite (1: 2); The DNA content between Guangfeng medicinal yam plantlets and its potted seedlings had no significant difference. CONCLUSION: A fast and efficient micropropagation in vitro technological system of stems with a bud of Guangfeng medicinal yam is established, and the flow cytometry detect results also show the genetic stability of Guangfeng medicinal yam plantlets, whose results provide the technical and theoretical basis for the large-scale production of Guangfeng medicinal yam plantlets. PMID- 27356372 TI - [Effects of Browning Inhibitors on Suspension Cells Growth and Secondary Metabolites Production in Changium smyrnioides]. AB - OBJECTIVE: To study the effects of browning inhibitors on Changium smyrnioides suspension cells growth and secondary metabolites production. METHODS: Different concentrations of V(C), AC, AHC, Na2S2O3 and PVP were added to the light brown suspension cells, and the contents of phenols, total coumarins, bergaptol and bergapten were determined by UV-Vis and HPLC. RESULTS: PVP with low concentration and V(C) improved the growth of the suspension cells in different degrees. It was showed that the content of phenols in the suspension cells was related to the kinds of browning inhibitors. The addition of V(C) in the medium increased the content of total coumarins significantly. After using 2 mg/mL of V(C), the gross increase rate of total coumarins was 51.53%, which was 4.8 times than that of the control group. The browning phenomenon caused by salicylic acid were inhibited by adding 2 mg/mL of V(C) into suspension culture system (with salicylic acid as the inducer). At the same time, the content of bergaptol and bergapten was increased 25.96% and 33.33%, respectively. CONCLUSION: V(C) is the best anti-browning agent in this study. It can inhibit browning, and promote cell growth and accumulation of secondary metabolites in Changium smyrnioides suspension cells. PMID- 27356373 TI - [A New Pest of Amomum villosum in Xishuangbanna]. AB - OBJECTIVE: To report a new pest of Amomum villosum and its distribution, occurrence regularity and damage situation, in order to provide reference for its control. METHODS: Reared the pest larvae, observed the morphological characters, and made a preliminary investigation on its distribution, occurrence regularity and damage situation. RESULTS: Through macroscopic examination, the pest was identified as Anisodera rugulosa, which distributed in the main producing areas of Amomum villosum in Xishuangbanna, the pest larvae ate the inside of Amomum villosum fruit, which made the fruit formed holes, more seriously, it made the whole fruit rot black. CONCLUSION: The pest causes the fruit yield reduction of Amomum villosum. Pest control work needs to be carry out as soon as possible. PMID- 27356374 TI - [Determination of Nucleosides and Nucleobases in Natural, Cultured and Tissue Culture Anoectochilus roxburghii Using LC-MS]. AB - OBJECTIVE: To establish a method for simultaneous determination of nucleosides and nucleobases in natural, cultured and tissue culture Anoectochilus roxburghii by high performance liquid chromatography-electrospray ionization/ion trap mass spectrometry (HPLC-ESI/MS). METHODS: The separation was performed on a Welch Ultimate XB-C18 column (250 mm x 4.6 mm,5 MUm). 20 mmol/L ammonium acetate solution and methanol were adopted as the mobile phase with gradient elution. The flow rate was 1.0 mL/min. The injection volume was 20 MUL. The column temperature and UV wavelength were set at 30 degrees C and 260 nm, respectively. RESULTS: Cytosine, uracil, cytidine, uridine, hypoxanthine, adenine, inosine, guanosine,fl thymidine and adenosine were identified in natural, cultured and tissue culture Anoectochilus roxburghii. The total content of nucleosides and nucleotides in Anoectochilus roxburghii were 1.6639, 1.8568 and 2.2013 mg/g,respectively. CONCLUSION: The contents of nucleosides and nucleobases in herb are affected by its growth pattern. The total content of nucleosides and nucleotides was tissue culture herb > cultured herb > natural herb. This investigation would provide the theoretic basis for quality standards and applications of Anoectochilus roxburghii in clinical research. PMID- 27356375 TI - [Comparative Study on Volatile Constituents of Plumeriae Flos from Different Origins]. AB - OBJECTIVE: To compare the volatile constituents of Plumeriae Flos from different origins. METHODS: Water distillation method according to the Chinese Pharmacopeia was used to extract the volatile constituents of fresh Plumeriae Flos samples (red flower and white flower) and dried samples. GC-MS method combined with NIST MS Search 2.0 data base was carried out to identify the volatile constituents and to calculate the relative percentage content. RESULTS: 55 peaks were detected in the GC-MS spectrum. Among of them, 26 volatile constituents were confirmed and calculated, which were mainly fatty alcohols and esters. The relative percentage content of geranyl benzoate in fresh Plumeriae Flos samples was significantly higher than the dried samples. CONCLUSION: The compositions of volatile constituents in Plumeriae Flos have no obvious correlation with the color of flowers, but are related to the flower fresh or dried. PMID- 27356376 TI - [Identification of Ardisiae Japonicae Herba by ITS2 Sequence]. AB - OBJECTIVE: The ITS2 sequence was used to identify Ardisiae Japonicae Herba collected from the market, in order to ensure the medicine quality of the market and to provide a reliable technical method. METHODS: The certified samples, including Ardisia japonica and its adulterants, were 56 samples of 17 species. All the sequences of the samples including six related sequences downloaded from NCBI were analyzed by computing the Kimura 2-parameter (K2P) genetic distance and the neighbor-joining (NJ) phylogenetic tree, then the method of DNA barcoding identification technology of Ardisiae Japonicae Herba based on ITS2 sequence was established. Combined with online comparison of sequences, the method was used to detect 15 samples of Ardisiae Japonicae Herba from the market to distinguish authenticity. RESULTS: The maximum and the average intra-specific K2P genetic distance of Ardisia japonica were all less than the minimum and the average inter specific K2P genetic distance, and Ardisia japonica and its adulterants could be separated by computing the NJ phylogenetic tree. The identification results of online comparison and DNA barcoding identification were the same. In all of the 15 samples, 13 of them were genuine, and the other two samples were fake. CONCLUSION: The DNA barcoding identification technique method of Ardisiae Japonicae Herba is established based on ITS2 sequence, and it provides a reference method to distinguish the authenticity of Ardisiae Japonicae Herba quickly by gene recognition. PMID- 27356377 TI - [Correlation Between Functional Groups and Radical Scavenging Activities of Acidic Polysaccharides from Dendrobium]. AB - OBJECTIVE: To compare the radical scavenging activity of five different acidic polysaccharides, and to find the correlation with the functional groups. METHODS: Alkali extraction method and Stepwise ethanol precipitation method were used to extract and concentrate the five Dendrobium polysaccharides, and to determine the contents of sulfuric acid and uronic acid of each kind of acidic polysaccharides, and the scavenging activity to ABTS+ radical and hydroxyl radical. Functional group structures were examined by FTIR Spectrometer. RESULTS: Five kinds of Dendrobium polysaccharides had different ability of scavenging ABTS+ free radical and hydroxyl free radical. Moreover, the study had shown that five kinds of antioxidant activity of acidic polysaccharides had obvious correlation withuronic acid and sulfuric acid. The antioxidant activity of each sample was positively correlated with the content of uronic acid, and negatively correlated with the content of sulfuric acid. CONCLUSION: Sulfuric acid can inhibit the antioxidant activity of acidic polysaccharide but uronic acid can enhance the free radical scavenging activity. By analyzing the structure characteristics of five acidic polysaccharides, all samples have similar structures, however, Dendrobium denneanum, Dendrobium devonianum and Dendrobium officinale which had beta configuration have higher antioxidant activity than Dendrobium nobile and Dendrobium fimbriatum which had a configuration. PMID- 27356378 TI - [Identification and Comparison of Constituents of Different Processed Products of Ligubtrum lucidum Fruit by HPLC Fingerprint]. AB - OBJECTIVE: To identify and compare the constituents in different processed products of Ligubtrum lucidum fruit by HPLC fingerprint, in order to study the changes of chemical constituents before and after processing. METHODS: HPLC analysis was carried outwith the mobile phase of acetonitrile and 0.1% formic acid in a gradient elution mode. The number of HPLC fingerprint chromatographic peaks and peak area changes in two processed products and the crude product under 240 nm and 280 nm were compared. Then the obtained fingerprint chromatographic peaks were confirmed according to the the standard references. RESULTS: 40 chromatographic peaks were detected from Ligustrum lucidum fruit, of which 18 chromatographic peaks were confirmed, including eleven iridoids, five phenethyl alcohols, one flavonoid and one aldehyde. 38 chromatographic peaks were detected from both steaming with wine product and the steamed product, of which 15 chromatographic peaks were confirmed, including seven iridoids, five phenethyl alcohols, one flavonoid, one aldehyde and one organic acid. There was a significant difference of fingerprint among crude Ligustrum lucidum fruit and its two processed products, but little difference between steaming with wine product and the steamed product. CONCLUSION: HPLC fingerprint of the steaming with wine product and the steamed product of Ligustrum lucidum fruit are similar while the changes on chemical composition and the content in steaming with wine product and steamed product of Ligustrum lucidum fruit are remarkable. PMID- 27356379 TI - [Macroscopic and Microscopic Identification of Ganoderma and The Confusable Medicinal Mushrooms of "Zhi"]. AB - OBJECTIVE: To compare the macroscopic and microscopic characteristics of Ganoderma and the confusable medicinal mushrooms of "Zhi". METHODS: The methods of macroscopic and microscopic examination were employed to authenticate Ganoderma and the other medicinal mushrooms of "Zhi" in the fungal group. RESULTS: The medicinal mushroom named "Zhi" could be distinguished from each other by the shape of pileus, stipe and the characteristics of mycelium and spore. CONCLUSION: There are abundant resources of fungal group from Ganodermataceae in China. The medicinal mushrooms of "Zhi", which are quite complicated in the market, are needed to be differentiated. PMID- 27356380 TI - [Chemical Constituents from Callicarpa nudiflora]. AB - OBJECTIVE: To study the chemical constituents of Callicarpa nudiflora. METHODS: The chemical constituents were isolated and purified by column chromatography on silica gel, ODS, Sephadex LH-20 and MPLC. Their structures were elucidated on the basis of physicochemical properties and special analysis. RESULTS: Eleven compounds were isolated from the leaves of Callicarpa nudiflora, whose structures were elucidated as 2alpha,3alpha-dihydroxyurs-12-en-28-oic acid (1), isorhamnetin (2), 2alpha,3beta,19alpha-trihydroxyurs-12-en-28-oic acid(3), 2alpha,3alpha,19alpha,23-tetrahydroxyurs-12-en-28-oic acid(4), 2alpha,3alpha,19alpha-trihyhydroxy-olean-12-en-28-O-alpha-D-glucopyranoside (5), benzyl-4'-hydroxy-benzoyl-3'-O-beta-D-glucopyranoside(6) (3S,5R,6R,7E,9S) megastigman-7-ene-3,5,6,9-tetrol(7), philonotisflavone(8), 1, 6-di-O-caffeoyl beta-D-glucopyranoside (9), luteolin-4'-O-(6"-E-caffeoyl)-beta-D-glucopyranoside (10), and (6S, 9R)-roseoside(11). CONCLUSION: All compounds are isolated from this plant for the first time. PMID- 27356381 TI - [Study on Phenylpropanoids of Gardenia jasminoides]. AB - OBJECTIVE: To investigate the phenylpropanoids constituents of Gardenia jasminoides. METHODS: Various column chromatography were used in the isolation and purification, physiochemical constant determination and spectral analysis were adopted to determine the chemical structures. RESULTS: Eight compounds were isolated from Gardenia jasminoides, including 4-hydroxy-cinnamic acid methylester (1), 3, 5-dimethoxy-4-hydroxy-cinnamic acid methylester (2), pisoninol II (3), 7 hydroxy-orebiusin A (4), (E) -3-(4'-hydroxyphenyl) -acrylic acid n-butyl ester (5), (E) -3-(4'-methoxyphenyl) -acrylic acid n-butyl ester (6), 4-methoxyl phenylpropanol n-butyl ether (7) and cycloolivil (8). CONCLUSION: All compounds are firstly isolated from this plant. PMID- 27356382 TI - [Ethyl Acetate-Soluble Chemical Constituents from Callicarpa kwangtungensis (II)]. AB - OBJECTIVE: To study the ethyl acetate-soluble chemical constituents of Callicarpa kwangtungensis. METHODS: The chemical constituents were isolated by column chromatography on silica gel, Sephadex LH-20 and MPLC. Their chemical structures were elucidated on the basis of special analysis. RESULTS: Eleven compounds were isolated from the ethyl acetate-soluble part of Callicarpa kwangtungensis, whose structures were elucidated as 4-methoxybenzoic acid (1), 3,4-dihydroxybenzoic acid (2), 4-hydroxy cinnamic acid(3), phenyl-beta-D-glucopyranoside (4), 3,4,5 trimethoxyphenyl-beta-D-glucopyranoside (5), 2alpha,3beta,22beta,23 tetrahydroxyursolic-12-en-28-oic acid (6), 2alpha,3beta,6beta,19alpha tetrahydroxy-urs-12-en-28-O-beta-D-glucopyranoside (7), 2beta,3beta,6beta,16alpha tetrahydroxy-olean-12-en-28-O-beta-D-glucopyranoside (8), (3S, 6E, 10R)-10-beta-D glucopyranosyloxy-3,11-dihydroxy-3,7,11-trimethyldodeca-1,6-diene (9), icariside C5(10), and (2E, 6E)-10-beta-D-glucopyranosyl-1, 11-dihydroxy-3, 7, 11 trimethyldodeca-2,6-diene (11). CONCLUSION: Compounds 4 - 11are isolated from Callicarpa genus for the first time, compounds 1 - 3 are isolated from this plant for the first time. PMID- 27356383 TI - [Chemical Constituents of Cynanchum auriculatum]. AB - OBJECTIVE: To study the chemical constituents of Cynanchum auriculatum. METHODS: Nine compounds were isolated by silica gel, RP-18 column chromatography and Sephadex LH20. RESULTS: Nine compounds were isolated from the ethanol extract of Cynanchum auriculatum. Their structures were determined as sarcosin-3-O-beta cymaropyranoside (1), cynotophylloside B (2), clemaphenol A (3), deacetylmetaplexigenin (4), methyl-2,6-dideoxy-3-O-methyl-beta-D-arabino hexopyranosyl- (1 --> 4) -6-deoxy-3-O-methyl-alpha-L-ribo-hexopyranoside (5), trans-p-hydroxy cinnamic methyl ester (6), cyclo(D-Pro-D-Leu) (7), 3alpha-hydroxy 5alpha ,6alpha-epoxy-7-megastigmen9-one (8) and ferulic acid methyl ester (9) on the basis of spectral analysis. CONCLUSION: Compounds 3, 5 and 6 - 9 are isolated from Cynanchum auriculatum for the first time. PMID- 27356384 TI - [Chemical Constituents in Petroleum Ether Extract of Mongolian Medicine Halenia corniculata]. AB - OBJECTIVE: To study the chemical constituents of Mongolian medicine Halenia corniculata. METHODS: Positive phase and reversed phase silica gel, as well as Sephadex LH-20 methods were used to separate and purify. The structure of the isolated constituents was identified according to the NMR spectroscopy data and the literature data. RESULTS: Nine compounds were isolated from 95% ethanol extracts of petroleum ether part of Halenia corniculata and identified as: 1 hydroxy-2,3,4,6-tetramethoxyxanthone (1), 1-hydroxy-2,3, 5-trimethoxyxanthone (2) 1-hydroxy-3,7-dimethoxyxanthone (3), 1-hydroxy-3,5,6,7,8-pentamethoxyxanthone (4), 1-hydroxy-2,3,4, 7-tetramethoxyxanthone (5), 1-hydroxy-3,5-dimethoxyxanthone (6),1-hydroxy-2,3,4,5,7-pentamethoxyxanthone (7), palmitic acid (8) and beta sitosterol (9). CONCLUSION: Compounds 3, 4 and 8 are isolated from this genus for the first time, Compound 1 is isolated from this plant for the first time. PMID- 27356385 TI - [Study on Chemical Constituents of Lonicera similis]. AB - OBJECTIVE: To study the chemical constituents of flower buds of Lonicera similis. METHODS: The compounds were isolated and repeatedly purified by macroperous resin, silica gel column, gel column, preparation of TLC, and RP C18, chromatography. Their structures were elucidated by physicochemical properties, MS and NMR. RESULTS: Seven compounds were isolated and identified as 4-hydroxy gamma,3,5-trimethoxybenzenepropanol (1), ursolic acid(2), E-ferulic acid(3), caffeic acid ethyl ester(4), dihydrosyringenin (5), rutin(6) and 6-Daucosterin (7). CONCLUSION: Compounds 1 and 5 are isolated from this genus for the first time, and compounds 2 - 4 are isolated from this plant for the first time. PMID- 27356386 TI - [Comparison of Chemical Components of Essential Oil from Ocimum basilicum var. pilosum Extracted by Supercritical CO2 Fluid and Steam Distillation]. AB - OBJECTIVE: To compare the chemical components of essential oil prepared by steam distillation extraction (SD) and supercritical CO2 fluid extraction (SFE-CO2) from Ocimum basilicum var. pilosum whole plant. METHODS: The essential oil of Ocimum basilicum var. pilosum were extracted by SD and SFE-CO2. The chemical components of essential oil were separated and analyzed by gas chromatography mass spectrometry( GC-MS). Their relative contents were determined by normalization of peak area. RESULTS: 40 and 42 compounds were detected in the essential oil prepared by SD and SFE-CO2 respectively. 25 compounds were common. CONCLUSION: Thereare significant differences of the chemical components between the Ocimum basilicum var. pilosum essential oil prepared by SD and thatby SFE CO2. Different methods showed different extraction efficiency with a special compound. It might be a good idea to unite several methods in the modern traditional Chinese medicine industry. PMID- 27356387 TI - [Effects of Germanium Concentrations on Germanium Accumulation and Biotransformation of Polysaccarified Germanium in Cordyceps militaris]. AB - OBJECTIVE: To study the effects of Germanium (Ge) concentration on Ge accumulation and biotransformation of polysaccarified Ge (PG) in Cordyceps militaris. METHODS: Solid and liquid culture were used in this study. RESULTS: In the solid culture conditions, when the Ge concentration of medium was 200 mg/L, the sporophore biomass of Cordyceps militaris was the maximum; and when Ge concentration was 300 mg/L,the amount of biotransformation of PG in sporophore was the highest; and when the Ge concentration is 250 mg/L, conversion rate of organic germanium (OG) in sporophore reached the highest value. In the liquid culture conditions, when the Ge concentration was 250 mg/L, the mycelium biomass of Cordyceps militaris was the maximum; and when Ge concentration was 150 mg/L, the amount of organic conversion of PG in mycelium was the most; and conversion rate of OG in mycelium was the highest in media with the Ge concentration of 200 mg/L. This study showed the germanium concentrations in 150 - 300 mg/L was more suitable for Ge accumulation and biotransformation of PG in Cordyceps militaris. In general, the biotransformation capacity to germanium of sporophore was stronger than that of mycelium of Cordyceps militaris. CONCLUSION: Germanium can significantly affect Ge accumulation and biotransformation of PG in Cordyceps militaris (P < 0.05) at different concentration. This result has practical value for Ge enriched cultivation of fruiting body in Cordyceps militaris. PMID- 27356388 TI - [Analysis of Monosaccharide Compositions in Paeoniae Radix Alba Polysaccharide]. AB - OBJECTIVE: To analyze the monosaccharide composition and the molar ratio of Paeoniae Radix Alba polysaccharide(PYPS). METHODS: Pre-column derivation HPLC method was developed to determine the monosaccharide composition and the molar ratio of PYPS from Paeonia lactiflora root of different growth years and obtained by graded alcohol precipitation. RESULTS: The results of HPLC analysis showed that PYPS consisted of Man, Rha, Glc, Ara, Gal and Xyl with the molar ratio of 156.26 : 0.73 : 0.85 : 1.03 : 1.17 : 0.79. Glc molar ratio increased gradually with the increasing of growth years, while the other five monosaccharides decreased. CONCLUSION: Precolumn derivation HPLC method can be used to determine the monosaccharides in PYPS, molar ratio are differently in the different growth years and molecular weight of the PYPS, Glc is the main monosaccharide of PYPS. PMID- 27356389 TI - [Protective Effects of Different Extracts of Imperatae Rhizoma in Rats with Adriamycin Nephrosis and Influence on Expression of TGF-beta1, and NF-kappaB p65]. AB - OBJECTIVE: To study the protective effect of Imperatae Rhizoma extract on renal tissues in rats with Adriamycin nephrosis, and to explore the possible mechanism. METHODS: The nephrosis model was induced by adriamycin 6.5 mg/kg intravenously in rats. The rats were randomly divided into seven groups, including normal group, model group, predisone group, petroleum ether groups, ethyl acetate group ,alcohol group, and water parts group, and treated for eight weeks. The protein content of 24 hours urine excretion was tested respectively by automatic biochemistry analyzer each week. After eight weeks, BUN, CRE, TCHO, TG, TP and ALB in serum were examined by automatic biochemistry analyzer. The TNF-alpha in serum was measured by ELISA. The expression of TGF-beta1, and NF-kappaB p65 in renal tissues were detected by immunohistochemistry respectively. The pathological changes in the renal were observed by light microscope. RESULTS: Compared with the model group ,the proteinuria of the rats in ethyl acetate group obviously reduced at the 6th, 7th, 8th week, the content of TNF-alpha in serum and the expression of TGF-beta1, and NF-kappaB p65 in renal tissues significantly reduced, but the content of TP and ALB in serum were increased obviously. In the alcohol and water parts groups ,the level of TG in serum and the protein content of 24 hours urine excretion of the 6th and 7th week were significantly decreased. The ethyl acetate, alcohol and water parts groups ameliorated the changes of pathology in renal. CONCLUSION: The different extracts of Imperatae Rhizoma had different protective effect in rats with adriamycin nephrosis, and the effect of ethyl acetate group was more stronger than that of other groups. The mechanism may be related to reducing the expression of NF-kappaB p65 and TGF-beta1, and the content of TNF-alpha inrenal tissues of rats. PMID- 27356390 TI - [Mechanism Study on Danggui Shaoyao San and Guizhi Fuling Wan For Treating Primary Dysmenorrheal Based on Biological Network]. AB - OBJECTIVE: To investigate the molecular mechanisms of Danggui Shaoyao San and Guizhi Fuling Wan for treating primary dysmenorrhea of liver depression and blood stasis syndrome by biological network method. METHODS: Targets of the formula were collected from. PubMed database, and targets of primary dysmenorrhea were searched from Gene Card database. Then, the "formula-syndromes-disease" network was constructed and analyzed with Cytoscape software. Molecular docking approach was used to verify estrogen-like effect of ingredients. RESULTS: The "formula syndromes-disease" shared multiple targets, which involves a variety of important nodes, such as IL and PGF2alpha, and played the effects of anti-inflammatory and analgesic. Danggui Shaoyao San could influence the function of hormones, such as corticotropin releasing hormone, and inhibit hyperactivity of adrenal axis. Guizhi Fuling Wan mainly affected a series of inflammation caused by cyclooxygenase and had the effects of blood coagulation. Estrogen-like effect of Danggui Shaoyao Sanwas stronger than that of Guizhi Fuling Wan. CONCLUSION: The novel approach will present an effective strategy for theory study of Danggui Shaoyao San and Guizhi Fuling Wan for treating primary dysmenorrhea. PMID- 27356391 TI - [Effects of Total Alkaloids of Harmaline on Learning and Memory in Vascular Dementia Rats]. AB - OBJECTIVE: To investigate the effects of total alkaloids of harmaline on learning and memory in vascular dementia rats, and its mechanism. METHODS: The model rats of vascular dementia were established with bilateral carotid artery ligation. After 30 days, the model rats were randomly divided into six groups: sham group, model group, nicergoline tablets 7 mg/kg group, and 25, 12.5 and 6.25 mg/kg dose groups of total alkaloids of harmaline, the rats were given medicine for 30 days. Learning and memory abilities were tested by Morris water maze, histomorphology in hippocampal CA1 area were observed by HE staining, BAX and BCL-2 protein expression in hippocampal CA1 area were detected by immunohistochemistry. RESULTS: Compared with model group, 25 mg/kg group of total alkaloids of harmaline shortened the incubation period in the third and fourth day significantly, 12.5 mg/kg group of total alkaloids of harmaline shortened the incubation period in the fourth day. 25 and 12.5 mg/kg groups of total alkaloids of harmaline significantly increased the times crossing the target. Total alkaloids of harmaline improved the neurons pathological changes of rat in the hippocampus CA1 area, 25 and 12.5 mg/kg of total alkaloids of harmaline downregulated the expression of apoptosis proteins BAX, upregulated the protein expression of BCL-2. CONCLUSION: Total alkaloids of harmaline can improve the learning and memory abilities in vascular dementia rats, which probably is related to inhibiting apoptosis of hippocampus cell. PMID- 27356392 TI - [Comparative Study on Effects of Anti-contusion Injury, Analgesia and Anti inflammation of Root and Stem of Zanthoxylum nitidum]. AB - OBJECTIVE: To provide the scientific evidence for expansion of medicinal parts of Zanthoxylum nitidum by comparing the effects of anti-contusion injury, analgesia and anti-inflammation of its root and stem. METHODS: The pharmacological effects between root and stem of Zanthoxylum nitidum were compared by observing the anti injury effect in rats with injury struck by hammer. The analgesic effect in mice was evaluated by writhing test and hot plate test, and the anti-inflammatory effect on paw edema induced by carrageenan and granuloma induced by cotton pellet were investigated in rats. RESULTS: Both root and stem of Zanthoxylum nitidum relieved the exterior and histological symptoms of rats' injury legs struck by hammer, decreased the numbers of mice's writhing, enhanced pain threshold of mice on heat plate, inhibited the edema of rats induced by carrageenan, and suppressed the granuloma of rats induced by cotton pellet. CONCLUSION: Stem of Zanthoxylum nitidum has similar effects of anti-contusion injury, analgesia and anti inflammation with root of Zanthoxylum nitidum. PMID- 27356393 TI - [Characteristic Chromatograms Analysis and Simultaneous Determination of Six Marker Components in Xinnaojian Capsules]. AB - OBJECTIVE: To establish an HPLC method for characteristic chromatograms analysis and simultaneous determination of six marker components in Xinnaojian Capsules from different manufactories. METHODS: Using HPLC, an Agilent C18 column (100 mm x 4.6 mm, 2.7 MUm) was adopted with acetonitrile-0.05% phosphoric acid as the mobile phase in a gradient elution mode, the flow ratewas 0.4 mL/min, the detection wavelength was 280 nm, and the column temperature was 40 degrees C. RESULTS: Totally eleven common peaks were recognized with epigallocatechin-3 gallate as the reference peak. There were good similarities between the standard characteristic chromatogram and each characteristic chromatogram of the 26 samples with their similarities over 0.99. The six marker components (gallic acid, gallocatechin, caffeine, epigallocatechin, epigallocatechin-3-gallate and epicatechin gallate) were separated well. Good correlation coefficients were found (r > 0.9990) and the average recovery rates ranged from 95.29% to 102.3%. CONCLUSION: The established method has high sensitivity and specificity, and can be used for the quality control of Xinnaojian Capsules. PMID- 27356394 TI - [Preparation Technology of Huayu Xiaozhong Spray Films]. AB - OBJECTIVE: The extraction process and film-forming preparation technology of Huayu Xiaozhong spray film was optimized respectively by orthogonal design and central composite design/response surface method (CCD-RSM). METHODS: With the extraction rate of amygdalin as the index, the orthogonal experiment was adopted for the optimization of extraction process. With the film-forming time, spraying effect, thickness and maintain time of spray film as the indexes, the dosages of PVA 1788, PVP k30 and glycerin as factors, the prescription was optimized by CCD RSM. RESULTS: The optimal extract processing was: immersing rude powder with 12 times of 60% ethanol for 24 hours. The optimal formula of Huayu Xiaozhong spray film was 5% of PVA 1788, 4.5% of glycerin and 5% of PVP-k30. CONCLUSION: Under the optimum condition, the extraction efficiency of amygdalin is 96.7%. Under the optimum technological condition of preparation, the spray film meets the demand of quality. PMID- 27356395 TI - [Preparation of Baicalein Liposome-Lyophilized Powder and Its Pharmacokinetics Study]. AB - OBJECTIVE: To prepare baicalein liposome-lyophilized powder, and to investigate the particle size distribution, encapsulation efficiency, stability, in vitro release and in vivo pharmacokirietics in rats. METHODs: Baicalein liposome was prepared by the ethanol injection, the encapsulation efficiency was measured by column chromatography, glucose, lactose and mannitol were selected as lyoprotectants. Pharmacokinetics study in rats was carried out by oral administration and analysis of rats pharmacokinetic parameters. RESULTS: The baicalein liposomes were spherical, the mean diameter was (93.1 +/- 11.2) nm, PDI was 0.258, the encapsulation efficiency was (83.9 +/- 0.4)%. In vitro release test results showed that it had a significant slow-release effect, freeze-dried mannitol for the best protective agent. The pharmacokinetic parameters of baicalein liposomes and solution were as follows: AUC(0 --> 24 (129.04 +/- 12.73) MUg/mL x h and (73.31 +/- 9.34) MUg/mL x h; C(max) (15.07 +/- 3.13) MUg/mL and (9.38 +/- 2.42) MUg/mL; T(max) 1 and 1.5 h. CONCLUSION: Baicalein liposome has the higher entrapment efficiency and the smaller particle size. In vitro studies show that baicalein liposome has a slow-release effect and can significantly improve the bioavailability in rats. PMID- 27356396 TI - [Implementation of precision control to achieve the goal of schistosomiasis elimination in China]. AB - The integrated strategy for schistosomiasis control with focus on infectious source control, which has been implemented since 2004, accelerated the progress towards schistosomiasis control in China, and achieved transmission control of the disease across the country by the end of 2015, which achieved the overall objective of the Mid- and Long-term National Plan for Prevention and Control of Schistosomiasis (2004-2015) on schedule. Then, the goal of schistosomiasis elimination by 2025 was proposed in China in 2014. To achieve this new goal on schedule, we have to address the key issues, and implement precision control measures with more precise identification of control targets, so that we are able to completely eradicate the potential factors leading to resurgence of schistosomiasis transmission and enable the achievement of schistosomiasis elimination on schedule. Precision schistosomiasis control, a theoretical innovation of precision medicine in schistosomiasis control, will provide new insights into schistosomiasis control based on the conception of precision medicine. This paper describes the definition, interventions and the role of precision schistosomiasis control in the elimination of schistosomiasis in China, and demonstrates that sustainable improvement of professionals and integrated control capability at grass-root level is a prerequisite to the implementation of schistosomiasis control, precision schistosomiasis control is a key to the further implementation of the integrated strategy for schistosomiasis control with focus on infectious source control, and precision schistosomiasis control is a guarantee of curing schistosomiasis patients and implementing schistosomiasis control program and interventions. PMID- 27356397 TI - [Integration and demonstration of key techniques in surveillance and forecast of schistosomiasis in Jiangsu Province III Development of a machine simultaneously integrating mechanized environmental cleaning and automatic mollusciciding]. AB - OBJECTIVE: To develop a machine simultaneously integrating mechanized environmental cleaning and automatic mollusciciding and to evaluate its effectiveness of field application, so as to provide a novel Oncomelania hupensis snail control technique in the large-scale marshlands. METHODS: The machine simultaneously integrating mechanized environmental cleaning and automatic mollusciciding, which was suitable for use in complex marshland areas, was developed according to the mechanization and automation principles, and was used for O. hupensis snail control in the marshland. The effect of the machine on environmental cleaning and plough was evaluated, and the distribution of living snails was observed at various soil layers following plough. The snail control effects of plough alone and plough followed by mollusciciding were compared. RESULTS: The machine could simultaneously complete the procedures of getting vegetation down and cut vegetation into pieces, plough and snail control by spraying niclosamide. After plough, the constituent ratios of living snails were 36.31%, 25.60%, 22.62% and 15.48% in the soil layers at depths of 0-5, 6-10, 11 15 cm and 16-20 cm respectively, and 61.91% living snails were found in the 0-10 cm soil layers. Seven and fifteen days after the experiment, the mortality rates of snails were 9.38% and 8.29% in the plough alone group, and 63.04% and 80.70% in the plough + mollusciciding group respectively (chi27 d = 42.74, chi215 d = 155.56, both P values < 0.01). Thirty days after the experiment, the densities of snails were 3.02 snails/0.1 m2 and 0.53 snails/ 0.1 m2 in the soil surface of the plough alone group and the plough + mollusciciding group, which decreased by 64.92% and 93.60%, respectively, and the decrease rate of snail density was approximately 30% higher in the plough + mollusciciding group than that in the plough alone group. CONCLUSIONS: The machine simultaneously integrating mechanized environmental cleaning and automatic mollusciciding achieves the integration of mechanical environmental cleaning and automatic niclosamide spraying in the complex marshland areas, which provides a novel technique of field snail control in the large-scale setting in China. PMID- 27356398 TI - [Study on immune status of patients with schistosomiasis japonica in Poyang Lake region III Humoral and cellular immune characteristics between Schistosoma japonicum high and low antibody responders]. AB - OBJECTIVE: To explore the immune mechanism of negative results of immune tests of schistosomiasis japonica patients. METHODS: Totally 142 schistosomiasis patients (positive stool examinations) of Poyang Lake region were tested by ELISA method, and the ROC curve was applied to determine the high and low response of the patients. The levels of cellular immunity and cytokines of high and low responders were compared. RESULTS: Totally eight schistosomiasis patients were found as low responders. Besides SWAP-IgA (t = -1.588, P > 0.1), the levels of isotype antibodies were significantly lower in the low responders compared with those in the high responders (t = -14.517 to -2.866, all P < 0.05). In the low responders, the propor- tion of CD3+T was increased; and the proportions of CD4+T, CD8+T, CD4+CD25+Treg, and the ratio of CD4+/CD8+ were all de- creased, but all of them were not significant (t = -1.72 to 0.974, all P > 0.05) compared with those in the high responders. The differences of IFN-gamma and IL-10 between the high and low responders were both not significant (t = -2.426 to 0.216, all P > 0.05). CONCLUSIONS: There is a significant difference between the high and low responders only in the levels of isotype antibodies. One of the reasons of low response in the immune tests is the much lower antibody level after the antigen antibody compound is completely formulated. PMID- 27356399 TI - [Serological diagnosis methods of schistosomiasis japonica at different prevalence: a meta-analysis]. AB - OBJECTIVE: To comprehensively evaluate the effects of indirect hemagglutination test (IHA) , enzyme-linked immunosorbent assay (ELISA), and dipstick dye method (DDIA) in the diagnosis of schistosomiasis japonica at different prevalence by using Meta-analysis. METHODS: Through the literature review according to the inclusion and exclusion criteria, a database was established, and by using Meta disc and R software, the Meta-analysis was performed including the threshold test, heterogeneity test, weighted by the quantitative effect of merger, SROC curve fitting, etc. RESULTS: A total of 60 papers were included in the final analysis. The sensitivities of IHA were 0.84, 0.76 and 0.94 in heavy, medium and low endemic areas, and specificities were 0.73, 0.64 and 0.73 respectively; the sensitivities of ELISA were 0.88, 0.80 and 0.93 in heavy, medium and low endemic areas, and the specificities were 0.59, 0.59 and 0.62 respectively; the sensitivities of DDIA were 0.93, 0.81 and 0.93 in the heavy, medium and low endemic areas, and specificities were 0.66, 0.69 and 0.59 respectively. The weighted sensitivities of IHA, ELISA and DDIA were 0.83, 0.87 and 0.90 respectively; the weighted specificities were 0.69, 0.60 and 0.62 respectively. The areas under the curve of SROC were 0.89, 0.96 and 0.92 in IHA, ELISA and DDIA respectively. CONCLUSIONS: In different prevalence, the effectiveness of different methods for serological diagnosis of schistosomiasis is different. The sensitivity and specificity of all diagnostic methods of schistosomiasis need to further improve. PMID- 27356400 TI - [Analysis of epidemic situation of malaria in Yunnan Province from 2011 to 2013]. AB - OBJECTIVE: To understand the epidemic situation and characteristics of malaria in Yunnan Province, so as to provide the reference for malaria elimination. METHODS: The data of malaria reported in the information system were collected and analyzed in Yunnan Province from 2011 to 2013. RESULTS: From 2011 to 2013, totally 2 256 malaria cases were found in Yunnan Province, with a morbidity of 0.162 8 per million and three of them were death cases. The local cases mainly distributed along the boundary and accounted for 29.48%, while the imported cases mainly came from Myanmar and accounted for 70.52%. The number of endemic counties with local malaria cases decreased from 37 to 10 during the three years. The number of imported cases reached the peak in May and the local cases in June. The patients were mainly aged from 20 to 49 years old (accounted for 70.58%), and 85.24% of the cases were peasants and laborers. Totally 86.66% of cases were laboratory confirmed cases, and 13.14% were clinically diagnosed. The proportions of cases reported by hospitals, health service centers and CDCs were 33.02%, 37.06% and 29.92%, respectively. CONCLUSIONS: The prevalence of malaria in Yunnan Province decreased from 2011 to 2013. The work of malaria cases double-checked by province-level CDCs is effective. However, the awareness and accurately diagnostic capability of clinical doctors still should be strengthened. PMID- 27356401 TI - [Epidemiological analysis of malaria prevalence in Shandong Province in 2014]. AB - OBJECTIVE: To understand the malaria epidemic situation and characteristics in Shandong Province in 2014, so as to provide evidences for taking targeted strategies and measures for malaria elimination. METHODS: The data of malaria epidemic and malaria cases of Shandong Province in 2014 were collected from Information Management System for Infectious Diseases Report and Information Management System for Parasitic Diseases Control and Prevention. The epidemiological characteristics of malaria situation and the diagnosis and treatment of malaria cases were analyzed by Microsoft Excel 2007. RESULTS: A total of 150 malaria cases were reported in Shandong Province in 2014, which increased by 14.50% compared with that in 2013 (131 cases). All the cases were imported from other countries except one imported from Yunnan Province in China, and most of the imported cases were from Africa (142 cases, 95.30%). All the cases were confirmed in Shandong Provincial Reference Laboratory and there were 121 cases (80.67%) infected with Plasmodium falciparum, 16 cases (10.67%) infected with P. vivax, 9 cases (6.00%) infected with P. ovale and 4 cases (2.67%) infected with P. malariae. The cases were mainly distributed in Tai'an (40 cases, 26.67%), Yantai (17 cases, 11.33%), Weihai (13 cases, 8.67%), Jining (11 cases, 7.33%) and Heze (11 cases, 7.33%) cities. CONCLUSIONS: There have been no local malaria cases reported in Shandong Province in the continuous 3 years. However, the reported number of imported malaria cases shows an increasing trend in the province in recent years, and the species of infected Plasmodium are diverse. Imported malaria from other countries is the key of malaria control in Shandong Province at present. PMID- 27356402 TI - [Cloning, expression and identification of gametocyte specific protein Pfgdv1 of Plasmodium falciparum]. AB - OBJECTIVE: To clone a gametocyte specific protein Pfgdv1 of Plasmodium falciparum, express and identify recombinant Pfgdvl protein in vitro. METHODS: PCR was performed to amplify Pfgdv1 from P. falciparum DNA which was got from the patient who was infected with P. falciparum, and the PCR product was inserted into pET28a (+) vector. pET28a-Pfgdv1 recombinant plasmid was constructed and transformed into E. coli host BL21 (DE3+). IPTG was used to induce the recombinant Pfgdv1 protein fused with His tag, and the protein was purified by His-NTA affinity chromatography. The recombinant protein was identified by SDS PAGE and Western blotting. RESULTS: The PCR product of Pfgdv1 gene was about 1.65 kb, meeting the expectation of predicted fragment size. The recombinant protein was about 67 kDa, which could be recognized by His-Tag monoclonal antibody. CONCLUSION: The Pfgdv1 gene of P. falciparum is successfully cloned, and the recombinant Pfgdv1 protein is expressed, thereby providing an opportunity for further study on transmission blocking vaccine. PMID- 27356403 TI - [Establishment and evaluation of loop-mediated isothermal amplification based on Plasmodium falciparum unique genes coding PHIST proteins]. AB - OBJECTIVE: To establish a novel convenient loop-mediated isothermal amplification (LAMP) method with the unique genes coding Plasmodium helical interspersed sub telomeric superfamily (PHIST) for the rapid molecular diagnosis of P. falciparum. METHODS: The unique genes coding PHIST with high expression mRNA profile during the ring form or schizont period of P. falciparum were screened and selected from the PlasmoDB database. The LAMP primers of targeted genes were designed by the online software (PrimerExplorer V4). The LAMP assay was executed by the color displaying method with SYBR Green. The dried blood spots of P. falciparum from clinical isolates were collected and the genomic DNA (gDNA) was extracted. For evaluation of sensitivity, the gDNA was diluted to four gradients (10-1, 10-2, 10 3, and 10-4). For assessment of specificity, the gDNA (s) of P. vivax, P. yoelii, Taenia saginata, and Schistosoma japonicum were also extracted. RESULTS: Totally, 61 P. falciparum unique genes coding PHIST were found. The PF3D7_1372300 with high expression value during the ring form and PF3D7_1401600 with high expression value during the schizont period were selected for LAMP assay. The lowest detectable limits of PF3D7_1372300 and PF3D7_1401600 were 130.5 parasite/ul and 1305.3 parasite/uL, respectively. Specific tests showed the amplified products of P. falciparum was positive and all the others including P. vivax, P. yoelii, T. saginata, and S. japonicum were negative. CONCLUSIONS: The established LAMP method with PF3D7_1372300 gene is sensitive, specific, simple and useful. It can be applied to the field investigation and clinical diagnosis for falciparum malaria. PMID- 27356404 TI - [Studies on immunogenicity and immunoprotection induced by heat shock protein 60 kDa of Schistosoma japonicum in mice]. AB - OBJECTIVE: To evaluate the immunogenicity and immunoprotective effect of heat shock protein 60 kDa (SjHSP60) of Schistosoma japonicum in mice after immunization and challenge infection, and explore the mechanism. METHODS: B cell/antibody-related databases and analysis tools were used to predict B-cell epitopes of SjHSP60. The mice were immunized with the recombinant SjHSP60 and challenged with S. japonicum cercariae. SjHSP60-specific antibodies in serum were detected by ELISA. The level of splenocyte proliferation was determined by 3H-TdR incorporation. Ex vivo suppression assay was performed to investigate the effects of CD4+CD25+ regulatory T cells (Tregs) induced by SjHSP60. RESULTS: SjHSP60 possessed multiple predominant regions of B-cell epitopes. SjHSP60 induced a significant increase in both SjHSP60-specific IgG levels (P < 0.01) and splenocyte proliferation (P < 0.01) with a higher IFN-gamma production (P < 0.01). However, the immunization with SjHSP60 resulted no significant reduction in adult worms (P > 0.05) and liver-accumulated eggs (P > 0.05) in S. japonicum infected mice. Ex vivo assay showed that CD4+CD25+ Tregs from SjHSP60-immunized mice enhanced immunosuppressive activity. CONCLUSION: SjHSP60 has a dual role in host immune system, being involved in the induction of dominant humoral and cellular immune responses as well as in the enhancement of immunosuppression. PMID- 27356405 TI - [Observation on growth status of Blastocystis hominis in three media]. AB - OBJECTIVE: To observe the growth situation of Blastocystis hominis in vitro and select the optimal method for cultivation of B. hominis in different media. METHODS: Ten positive stools with B. hominis were inoculated in three different media for cultivating, namely 1640, Jone's medium and vitro medium. And the stools with good growth status and high quantities of B. hominis were chosen to inoculate in the three media with equal amount after subcultivation, and the number of B. hominis was counted every 24 h for ten days, and the morphological changes and growth status were also observed. RESULTS: The densities of B. hominis in the 1640 and Jone's medium were higher than that in the vitro medium 48 h after the inoculation. The same stool sample was inoculated to the three different media and observed for ten days, and the results indicated that the growth of B. hominis presented regular changes in the three media, the growth peaks were on the third, sixth and ninth day post inoculation; and the density of B. hominis was the highest in the Jone's medium. The morphology of B. hominis was the clearest and most dynamic in the vitro medium, while various reproductive forms were observed in the Jone's medium. CONCLUSION: Jone's medium is suitable for the growth of B. hominis and can be the first choice for the cultivation of B. hominis in vitro, and vitro medium is the best medium for observing the growth situation of B. hominis. PMID- 27356406 TI - [Analysis of Oncomelania hupensis status in schistosomiasis surveillance sites of Yunnan Province in 2015]. AB - OBJECTIVE: To understand the Oncomelania hupensis distribution and infection status in the schistosomiasis surveillance sites of Yunnan Province, so as to provide the evidence for making the control and prevention measures. METHODS: Eighteen administrative villages were selected as the surveillance sites where the schistosomiasis endemic was serious in 18 epidemic counties, one village for one county. The snail status was investigated with the systematic sampling and environmental sampling methods, and the infection status of the snails was detected by a microscope and loop-mediated isothermal amplification (LAMP). The surveillance database was established and descriptively analyzed. RESULTS: In 2015, the total surveillance area was 1826.55 hm2, and the area with snails was 55.03 hm2, that was reduced by 57.70% as compared to that in 2013, and by 40.63% as compared to that in 2014. No new snail area was discovered, and also no schistosome infected snails were discovered. Totally 718,532 frames were surveyed, and the occurrence rate of frames with snails was 0.45% and the density of living snails was 0.013 9 snail/0.1 m2. In the endemic controlled areas, the snail area and density of living snails were both the highest. The snails concentrated on the environments of paddy field, ditch, bottomland, small reservoir, and dry land, and the vegetations of rice, dry crop, weed and wood. The snail area, occurrence rate of frames with snails, total number of snails and number of living snails all showed a downward trend. No infected snails were found for three years. CONCLUSIONS: The Oncomelania hupensis snails have been effectively controlled in the national schistosomiasis surveillance sites of Yunnan Province. However, the comprehensive snail control measures still should be continually strengthened in order to consolidate the achivements. PMID- 27356407 TI - [Development and application of communication materials for participatory health education of schistosomiasis in fishermen and boatmen of Poyang Lake region]. AB - OBJECTIVE: To design and develop new types of health education materials which are suitable for fishermen and boatmen in endemic areas of marshland and lake regions, and to observe their application effects. METHODS: A total of 292 adult fishmen and boatmen who lived in Houshan Village, Yugan County, the schistosomiasis endemic area of Poyang Lake Region, were selected randomly and investigated by questionnaires to understand the status of their knowledge, attitudes, practices on schistosomiasis control as well as the channels for getting information on schistosomiasis control and the materials that they were willing to accept. Then the information and materials suitable for the target population were developed together by the researchers and the volunteers of the villagers through focus group discussions, personal interviews and the Delphi method. RESULTS: A series of participatory health education materials of schistosomiasis control targeted to the fishmen and boatmen were developed, including 2 live posters, 2 picture puzzles, 2 short opusculums and one song about schistosomiasis control. The field application showed that 98.97%, 84.38%, 78.35% and 80.93% of the participants considered those materials had scientificity, intelligibility, interestingness and practicability, respectively. CONCLUSION: The participatory health education materials of schistosomiasis control is suitable for fishmen and boatmen, which can be used for reference by other endemic areas in marshland and lake regions. PMID- 27356408 TI - [Impact of ecological protection construction on schistosomiasis transmission of Qionghai Lake wetland in Xichang City]. AB - OBJECTIVE: To understand the impact of Qionghai Lake wetland ecological protection construction on the prevalence of schistosomiasis, so as to provide the evidence for formulating the strategies for schistosomiasis control and prevention. METHODS: A retrospective survey of the construction of Qionghai Lake wetland was performed, and eleven villages around the wetland were surveyed for schistosomiasis endemic situation. The influence of the wetland project on the schistosomiasis prevalence and Oncomelania hupensis snail status were investigated. RESULTS: Before the construction of Qionghai Lake wetland, the snail elimination and extended chemotherapy for residents was performed. After the project was finished, the roads and ditches were hardened. From 2009 to 2014, the schistosome infection rate of residents declined from 0.37% to 0. No schistosome infected snails were found and in recent 2 years, no snails were found. No mice were infected in the sentinel tests. CONCLUSIONS: The construction of Qionghai Lake wetland effectively eliminates snails, and interrupts the transmission of schistosomiasis. However, the environment of the wetland is more suitable for snail breeding, and therefore, the surveillance still should be strengthened. PMID- 27356409 TI - [Analysis of imported malaria situation in Liyang City, Jiangsu Province]. AB - OBJECTIVE: To analyze the epidemic characteristics of imported malaria in Liyang City, so as to provide the evidence for formulating appropriate control strategies and measures. METHODS: The malaria epidemic situation reports, case epidemiological investigations and the follow-up materials of counterparts returned together with the cases were collected and analyzed in Liyang City from 2007 to 2014. RESULTS: Totally 53 imported malaria cases were reported and they were all laboratory confirmed in Liyang City from 2007 to 2014. Forty-nine cases (92.5%) were imported from African countries, 37 cases (69.8%) were Plasmodium falciparum infection, and 37 cases (69.8%) had overseas incidence history. Forty cases (75.5%) were aged between 30 and 49 years, and 52 cases (98.1%) were male, 42 cases (79.2%) were farmers. These cases were distributed in all the 10 towns and there were no obvious seasonal variation for onset time. The median time from onset to seeing a doctor was 3 d, and the median time from seeing a doctor to being diagnosed was 0 d. The first visit health facilities by the patients were various, and the diagnostic health facilities were all the medical institutions at the county level or above, and the standardized treatment rate was 100%. CONCLUSION: During the last 5 consecutive years, there have been no local infected malaria cases in Liyang City, and the remarkable results have been achieved in malaria elimination. However, there are still many imported malaria cases, and the infected species are diverse. Therefore, the imported malaria is still the key of malaria prevention and control. PMID- 27356410 TI - [Effect of malaria control in Shayang County from 1995 to 2014]. AB - OBJECTIVE: To evaluate the effect of malaria control in Shayang County from 1995 to 2014, so as to provide the evidence for the strategy revision of the elimination of malaria prevention and control. METHODS: The data of malaria surveillance were collected and analyzed in Shayang County from 1995 to 2014. RESULTS: During the 20 years, 582 malaria patients (9 imported patients) were reported. The average annual incidence rate was 0.53/ten thousand. Through the comprehensive prevention and control measures, the incidence of malaria decreased from 2.30/ten thousand in 1997 to 0.02/ten thousand in 2010, and the decreasing rate was 99.13%. The proportion of malaria cases in the total infectious diseases cases also decreased from 21.23% in 1997 to 0.07% in 2010, and the decreasing rate was 99.67%. There were no local malaria patients from 2010 to 2014. However, the imported malaria patients were increased year by year during the recent years. CONCLUSIONS: This county has reached the national malaria control and elimination standards, and the malaria control work has been transferred from the control period to the elimination phase. We should implement the prevention and control measures and strictly control imported malaria, so as to consolidate the malaria control results. PMID- 27356411 TI - [Analysis of malaria endemic situation in Jingmen City from 2005 to 2014]. AB - OBJECTIVE: To analyze the malaria endemic situation in Jingmen City from 2005 to 2014, so as to provide the evidence for revising the measures of malaria elimination. METHODS: The malaria endemic data of Jingmen City from 2005 to 2014 were collected and analyzed. RESULTS: Totally 516 malaria cases were reported during the 10 years in Jingmen City, and the average annual malaria incidence was 0.17/10 000, which was declining year by year. The local infection of malaria cases were 484 (accounted for 93.80%) with obvious aggregation in June, July and August, which were also relatively aggregated in farmers (accounted for 60.08%). The ratio of male to female was 1.93:1. No local cases of malaria infection were reported from 2012 to 2014. The imported malaria cases were 32 (accounting for 6.20%), showing a rising trend in recent years. CONCLUSION: The incidence of malaria is low and has a downward trend year by year from 2004 to 2015 in Jingmen City. However, the imported malaria cases are increasing in recent years, and the surveillance and management of them should be paid more attention to. PMID- 27356412 TI - [Development and application of Jingcen DY-1 spraying tanker for Oncomelania hupensis snail control]. AB - OBJECTIVE: To develop a Jingcen DY-1 type spraying tanker for Oncomelania hupensis snail control and evaluate its effect of field application as well as the cost. METHODS: The currently available tractor was used as a vector, and the mechanical and electrical equipments and containers were integrated with shafts, pipelines and electric lines to produce a spraying tanker for snail control, with the functions of carrying people and molluscicides, generating electric power and getting water, mixing stocking solutions, adjusting molluscicide solutions evenly, and spraying drugs. The volume of the molluscicide solution, flow rate of water injection, and the flow rate, range and advance speed of the spray gun were tested, and the solution concentrations of molluscicide in the tanker and at the muzzle of the spray gun at different time were detected. Meanwhile, the molluscicidal effect and cost of the spraying tanker were analyzed by the field test. RESULTS: The volume of the liquid storage pot of the Jingcen DY-1 type spraying tanker was 1 800 L, the flow rate of water injection was 400 L/min, the flow rate and the spray range of the standard spray gun were 110-200 L/min and 19.70-23.50 m, respectively, the efficiency of drug spraying of the spraying tanker was 6 000 m/h, and the ratio of spray width (m) to march speed (m/min) was 1:200. When 5 min post mother liquid recirculating, the average concentration of the molluscicide at the upper-, middle- and lower-layers of the liquid storage pot was (1030.39 +/- 43.00) mg/L, with a variation coefficient of 4.17%. The average concentration of the molluscicide in the spraying process (spraying for 2, 4, 6, 8, 9 min) was (953.00 +/- 68.87)mg/L, with a variation coefficient of 7.22%. The concentration of the residual drug in the liquid storage pot post spraying was 1 000.43 mg/L, which reached the effect concentration for snail control. After spraying for 7 days in the field, the average density of living snails reduced by 88.20% as compared to that before spraying, and the adjusted mortality of snails was 87.65%. The unit cost of Jingcen DY-1 spraying tanker was 0.086 7 Yuan/m2. which reduced by 58.20% as compared to that of the conventional spraying tanker. CONCLUSIONS: Jingcen DY-1 type spraying tanker for snail control which integrates various equipments together can effectively control the concentration and dose of the molluscicide, and the machine is labor-saving, efficient, economic and well adapted, and is worthy to be widely applied. PMID- 27356413 TI - [Study on acute inhalation toxicity of Luowei, a plant molluscacide]. AB - OBJECTIVE: To study the acute inhalation toxicity of 50% Luowei, a plant molluscacide, in rats. METHODS: Twenty adult Wistar rats, half male and half female, were given of 5000 mg/m3 of 50% Luowei through a dynamic inhalation device and the death and recovery of the rats were observed within 14 days, and LC50 was drawn. RESULTS: After exposure, the activities of the rats decreased and a few individual animals had scratching symptom, but the symptom disappeared after the exposure. No animals died during the whole observation period. Therefore, the acute inhalation LC50 was greater than 5000 mg/m3 for rats, and Luowei belonged to low toxicity level. CONCLUSIONS: 50% Luowei will not cause animal death if it is inhaled into animal body. However, people still need to wear protective equipment in production and use. PMID- 27356414 TI - [Morphological observation on hypopus of Caloglyphus berlesei by optical microscope]. AB - OBJECTIVE: To understand the structure characteristics of hypopus of Caloglyphus berlesei. METHODS: The hypopus of C. berlesei was collected from the feed of Chinese Polyphaga, and was made into the conventional glass specimens. The structure characteristics of hypopus of C. berlesei were observed by an optical microscope. RESULTS: The hypopus of C. berlesei had 4 pairs of legs, and the foot claws and tarsus were well-developed. The structural features were shown, such as the setae of tibia and setae of genu. Genital plates were obviously ossified. CONCLUSION: The research on hypopus of Caloglyphus berlesei provides the reference for its further scientific classification and research on the life cycle. PMID- 27356415 TI - [GIS platform for real-time monitoring and early warning of forestry schistosomiasis-control project: a case study in Renshou County, Sichuan Province]. AB - OBJECTIVE: To real-timely monitor the environment in the forestry schistosomiasis control project (CFSCP) area and to early warn the status of Oncomelania hupensis snails in the schistosomiasis endemic area. METHODS: Based on ArcGIS Engine 10.1 software, the Geographic Information System (GIS) platform of the forestry schistosomiasis project of real-time monitoring, early warning and emergency management in Renshou County, Sichuan Province, was designed and established. RESULTS: The functions of the platform mainly included real-time monitoring of the environment in CFSCP area, and early warning of the crisis status of 0. hupensis snails, as well as editing the map of snail distribution, query, spatial analysis and other GIS functions. CONCLUSION: This platform could provide the scientific support to the forestry administrative department of the CFSCP area. PMID- 27356416 TI - [Investigation on source and dissemination way of knowledge on schistosomiasis prevention and control in population in Jingjiang City after transmission interrupted]. AB - OBJECTIVE: To understand the source of knowledge on schistosomiasis prevention and control and the acceptable degree on different propagation patterns of population in Jingjiang City after schistosomiasis transmission-interrupted, so as to provide the evidence for the production of suitable materials for health education. METHODS: The permanent residents, floating population as well as the primary school students in Grade 5 and 6 in riverside regions in Jingjiang City were selected as the investigation objects, the information propagation condition and the knowledge source, and the expected propagation patterns were investigated by questionnaires. RESULTS: The popularizing rates on the television, computer and mobile phone of the villagers were 99.81%, 84.16% and 87.78%, respectively. Both the two investigated schools had the independent TV network, broadcast and multimedia, and all the computer classroom could connected to Internet. The main sources on schistosomiasis control of permanent residents and floating population were folders and the exhibition board (62.0% and 40.5% respectively), the substantial material (42.0% and 33.5% respectively) and TV (40.5% and 36.0% respectively), while those of the students were video CD (100%), substantial material (99.5%) and folders and the exhibition boards (84.2%). The propagation ways with high acceptable degrees among the residents and floating population were substantial material, folders and the exhibition boards and short messages by mobile phone, while those among the students were video CD, substantial material, folders and the exhibition boards. CONCLUSION: The material on health education should be targeted to the demands of the different populations and their condition of information propagation, in addition, the Internet material should be developed and the communicational channels should be broaden. PMID- 27356417 TI - [IHA detection results of outpatients in schistosomiasis clinic, 2005-2014]. AB - OBJECTIVE: To understand the changes of positive rates of IHA detections of outpatients in schistosomiasis clinic. RESULTS: The data of IHA detections of outpatients in schistosomiasis clinic in Hubei Provincial Center for Disease Control and Prevention were collected and analyzed statistically from 2005 to 2014. RESULTS: A total of 7 113 outpatients were detected by IHA test, and 547 of them were positives with a positive rate of 7.69%. The positive rate of IHA test was on an upward slope before 2008, and the rate reached 14.85% in 2008, which was significantly higher than that in 2005 (5.81%) (chi2 = 47.40, P < 0.01), then it was on a declined stage after 2008, and the positive rate decreased to 3.76 in 2014, which was significantly lower than that in 2008 (chi2 = 12.29, P < 0.01). The positive rate of outpatients in the 10 ~ < 30 years age group was higher than those in other age groups (all P < 0.012 5), and the male positives were more than the female ones. CONCLUSIONS: The schistosomiasis endemic situation has been significantly decreased in Hubei Province. The male and people in 10 ~ < 30 age group are the high risk groups, so the targeted health education should be strengthened. PMID- 27356418 TI - [Analysis of schistosomiasis endemic situation in Yizhou City from 2011 to 2014]. AB - OBJECTIVE: To evaluate the effect of schistosomiasis control in Yizhou City, Guangxi Zhuang Autonomous Region, from 2011 to 2014, so as to provide the evidence for formulating the further prevention and control strategy. METHODS: The schistosomiasis surveillance data were collected and analyzed in Yizhou City from 2011 to 2014. RESULTS: From 2011 to 2014, 770.38 hm2 was surveyed for the Oncomelania hupensis snails, and two snail infested sites were found, while no infected snails were found. Totally 3,524 residents were tested by ELISA for Schistosoma japonicum infection, and 38 cases were positive. The positive rate of 2013 was significantly higher than those of other three years (chi2 = 15.08, P < 0.05). Totally 432 rats and 28 dogs were dissected and 1,697 cattle were examined by the stool test, but no positive cases were found. CONCLUSIONS: The indicators of schistosomiasis surveillance are basically stable in Yizhou City. PMID- 27356419 TI - [Epidemiological characteristics of imported malaria cases in Neijiang City, 2013]. AB - OBJECTIVE: To understand the epidemiological characteristics of imported malaria cases in Neijiang City in 2013, so as to provide the references for malaria elimination in the city. METHODS: The epidemiological data of malaria cases were collected from the Parasitic Diseases Information Management System of Chinese Center for Disease Control and Prevention, and the data were analyzed with the descriptive epidemiological method. RESULTS: Totally 19 cases of imported malaria cases were reported in Neijiang City in 2013, which was increased by 375% comparing to that in 2012 (4 cases) , and all the cases were confirmed by the laboratory. Among these cases, 14 were (73.68%) falciparum malaria cases, 5 (26.32%) were vivax malaria cases; 13 cases (68.42%) were from African countries, and the other 6 (31.58%) were from Southeast Asia. These cases were distributed throughout each quater, which had no significant seasonality. All the cases were male aged from 20-49 years, and the majority of them (16 cases, 84.21%) were farmers and workers. CONCLUSIONS: The prevention and control situation of imported malaria is severe in Neijiang City. The capacity construction of malaria diagnosis and treatment of basic medical institutions as well as the health education and monitoring and management to floating population should be strengthened. PMID- 27356420 TI - [Advances in researches on beta-carbonic anhydrases as anti-parasitic drug targets]. AB - beta-carbonic anhydrases (beta-CAs) are ubiquitous metalloenzymes which active site contains a zinc ion (Zn2+), and they could catalyze the hydration of carbon dioxide to bicarbonate and protons efficiently and are involved in many biological processes, such as respiration, pH and CO2 homeostasis, biosynthetic reactions, virulence regulation and so on, and may play a critical role in the life activity of many organisms which contain these enzymes. beta-CAs are widely distributed in fungi, bacteria, algae, plants and a small number of protozoan and metazoan except vertebrates. Therefore, as potential drug targets for designing and developing antibacterial and anti-parasitic drugs, beta-CAs promise a broad application prospect. This paper focuses on the distribution, physiological function and the progress of researches on beta-CAs in parasites and their vectors. PMID- 27356421 TI - [Advances in researches of molluscicidal microorganisms against Oncomelania hupensis]. AB - The elimination of Oncomelania hupensis snails is important to schistosomiasis control. Recently, the application of molluscicidal organisms is considered as a safe and efficient method for snail elimination. In order to provide scientific evidences for effective control of O. hupensis and schistosomiasis, this paper summarizes the researches of molluscicidal microorganisms against O. hupensis. PMID- 27356423 TI - New Chapters. PMID- 27356422 TI - [Progress of researches on lysozyme and its expression in Oncomelania hupensis]. AB - Lysozyme generally exists in animals, plants and microorganisms, and it is used as a natural anti-infection material and one of the important non-specific immune factors in organisms. This paper reviews the progress of researches on its classification, gene structure and function, and expression regulation in Oncomelania hupensis, and on the factors affecting its activities in recent years, in order to further discuss its distribution in O. hupensis. PMID- 27356424 TI - Issues to watch in September. PMID- 27356425 TI - Hope is not a strategy ... but decision-driven group planning is. PMID- 27356426 TI - Physician compensation, the Stark law and the courts. PMID- 27356427 TI - Optimize patient collections. Employ new strategies, technology to collect payments quickly, efficiently. PMID- 27356428 TI - Complying with the Hazard Communication Standard. Transition to a new 16-section SDS format will occur in stages and be fully operational by Dec. 1, 2016. PMID- 27356429 TI - 6 SOURCES OF FINANCIAL LEAKS IN YOUR PRACTICE AND HOW TO PLUG THEM. AB - While the big embezzlement cases get our attention, it's usually smaller sums taken over time by sophisticated employees who know how to exploit the gaps in your internal financial controls and avoid detection. Learn how to identify vulnerabilities early on and protect your group. PMID- 27356430 TI - Challenging the status quo. PMID- 27356431 TI - In the weeds: Increasing operational demands hamper strategic planning. PMID- 27356432 TI - Sharing means caring: Clinical integration requires tracking, sharing clinical quality data. PMID- 27356433 TI - Preparing for future patient care delivery models. PMID- 27356434 TI - Changing with the times: MGMA revises 'Medical Practice Today' survey. PMID- 27356435 TI - BOK revision reflects industry changes. Updated resource applicable to practice managers in every setting. PMID- 27356436 TI - Capitalize on technology: Create digital forms. PMID- 27356437 TI - Going viral: Creating sick-policy guidelines. PMID- 27356438 TI - Sign on the dotted line: How to drive no-show rates to 1.7%. PMID- 27356439 TI - Practice management: A true calling An MGMA member ministers to prisoners. PMID- 27356440 TI - Editorial. PMID- 27356441 TI - Interview With Linda J. Knodel, FACHE, Senior Vice President and Chief Nursing Officer at Mercy. PMID- 27356442 TI - Five Ideas for the Development of Successful Physician Leaders. PMID- 27356443 TI - Evolving Physician Reimbursement Structures: Moving the Medical Group to Value Based Success. PMID- 27356445 TI - Practitioner Application. PMID- 27356444 TI - Medical Assistants as Flow Managers in Primary Care: Challenges and Recommendations. AB - As healthcare organizations look for ways to reduce costs and improve quality, many rely increasingly on allied healthcare professionals and, in particular, medical assistants (MAs) to supplement the work of physicians and other health professionals. MAs usually work in primary care, where they often play important roles on healthcare teams. Drawing on an empirical study of a large, multispecialty delivery system engaged in reconfiguration of primary care, we found that using MAs as flow managers required overcoming several challenges. These included entrenched social and occupational hierarchies between physicians and MAs, a lack of adequate training and mentorship, and difficulty attracting and retaining talented MAs. We offer several recommendations for healthcare organizations interested in using MAs as flow managers in their practices. PMID- 27356446 TI - Transformational Leadership and Change: How Leaders Influence Their Followers' Motivation Through Organizational Justice. AB - In the past decade, the reform of Quebec's healthcare establishments has resulted in a reduction in the number of institutions through mergers and closures. In this report, we investigate the consequences of reform by looking at managers' motivations and related mitigating factors. We examine the influence that transformational leaders have on their employees' motivation through organizational justice. Using a survey of 253 healthcare managers, we describe how the positive impact of transformational leadership on motivation is fully mediated via different aspects of organizational justice. The results indicate that while transformational leaders influence each type of organizational justice, followers' motivation is affected primarily by procedural and interpersonal justice and little by distributive justice. PMID- 27356447 TI - Practitioner Application. PMID- 27356448 TI - Succession Planning and Financial Performance: Does Competition Matter? AB - Succession planning has been defined as the process by which one or more successors are identified for key positions, development activities are planned for identified successors, or both. Limited research exists pertaining to the relationship between hospital succession planning and financial performance, particularly in the context of market competition. We used the resource-based view framework to analyze the differential effect of succession planning on hospitals' financial performance based on market competition. According to RBV, organizations can achieve higher performance by using their superior resources and capabilities. We used a panel design consisting of a national sample of hospitals in the United States for 2006-2010. We analyzed data using multivariate linear regression with facility random effects and year and state fixed effects. The sample included 22,717 hospital-year observations; more than one half of the hospitals (55.4%) had a succession planning program. The study found a positive relationship between the presence of succession planning and financial performance (beta = 1.41, p < .01), which was stronger in competitive markets (beta = 2.31, p = .03) than in monopolistic markets (beta = 1.06, p = .01). Hospitals can use these results to make informed decisions about investing in succession planning programs on the basis of competition in their market. PMID- 27356449 TI - Practitioner Application. PMID- 27356450 TI - Transitions of Care in an Era of Healthcare Transformation. AB - In the practice of modern emergency medicine (EM), transitions of care (TOC) have taken a prominent role, and during this time of healthcare reform, TOC has become a focal point of improvement initiatives across the continuum of care. This review includes a comprehensive examination of various regulatory, accreditation, and policy-based elements with which EM physicians interact in their daily practice. The content is organized into five domains: Accreditation Council for Graduate Medical Education (ACGME), The Joint Commission, Affordable Care Act, National Quality Forum (NQF), and accountable care organizations. This review is meant to be a synthesis of TOC material, tailored for EM physicians and the teams that make these departments run. We include (1) relevant current regulations and standards from various entities that are most likely to affect the day-to-day practice of EM; (2) examination of the consequences of these regulations and standards and how they can be used to shape EM practice and clinical decision making; and (3) comparison of interventions aimed at improving TOC, including evidence from current literature, practical examples, and proposals. Emergency departments must develop, implement, and monitor TOC programs and processes that can facilitate seamless and efficient care as patients transfer between settings. This report provides a framework for that effort and is designed to help EM physicians continue to take the lead in improving TOC to help shape the future of modern practice. PMID- 27356451 TI - Practitioner Application. PMID- 27356452 TI - The History and Future of the Midwest Multi-State Division. PMID- 27356453 TI - Impacting a Culture of Safety: One Nurse. PMID- 27356454 TI - Continuing Education Requirement for Licensure Renewal. PMID- 27356455 TI - Nurse Practitioners Ease Shortages. PMID- 27356456 TI - Nursing Licensure Improvements. PMID- 27356457 TI - Questions to Ask in Making the Decision to Accept a Staffing Assignment for Nurses. PMID- 27356458 TI - Optimal staffing. New resource aims to help RNs implement evidence-based staffing plans. PMID- 27356459 TI - Cardiac Resynchronization Therapy in Congestive Heart Failure Patients. PMID- 27356460 TI - A Relational Approach to Implantable Cardioverter-Defibrillator Generator Replacement: An Integrative Review of the Role of Nursing in Shared Decision Making. AB - BACKGROUND: Implantable cardioverter defibrillator (ICD) implantation rates are increasing as advances in heart failure and arrhythmia management progress. Consequently, the number of ICD generator replacements is rising and ICD replacement is an opportune time for shared decision-making (SDM). Nurses should have distinct roles and responsibilities in SDM processes. OBJECTIVES: To use a relational lens to localize the role of the nurse in SDM, and recommend ways in which nurses can be involved in SDM. METHODS: An integrative review of 17 articles was conducted to determine the role of nurses in SDM. RESULTS: Our analysis revealedfour themes that helped us articulate nurse involvement in SDM; knowledge as a basis for SDM, sharing power in the nurse-patient relationship, utilization of decisional support strategies, and communication. CONCLUSION: Our findings support the participation of nurses in SDM. Nursing implications are offered, specifically for the management of patients facing ICD replacement. PMID- 27356461 TI - Sampling Methods in Cardiovascular Nursing Research: An Overview. AB - Cardiovascular nursing research covers a wide array of topics from health services to psychosocial patient experiences. The selection of specific participant samples is an important part of the research design and process. The sampling strategy employed is of utmost importance to ensure that a representative sample of participants is chosen. There are two main categories of sampling methods: probability and non-probability. Probability sampling is the random selection of elements from the population, where each element of the population has an equal and independent chance of being included in the sample. There are five main types of probability sampling including simple random sampling, systematic sampling, stratified sampling, cluster sampling, and multi stage sampling. Non-probability sampling methods are those in which elements are chosen through non-random methods for inclusion into the research study and include convenience sampling, purposive sampling, and snowball sampling. Each approach offers distinct advantages and disadvantages and must be considered critically. In this research column, we provide an introduction to these key sampling techniques and draw on examples from the cardiovascular research. Understanding the differences in sampling techniques may aid nurses in effective appraisal of research literature and provide a reference pointfor nurses who engage in cardiovascular research. PMID- 27356462 TI - Impedance Cardiography-Guided Treatment of Hypertension: A Review of the Literature. AB - BACKGROUND: Hypertension occurs when regulatory mechanisms fail, resulting in increased cardiac output (CO) and/or increased systemic vascular resistance (SVR). Impedance cardiography (ICG) is a non-invasive technology that measures CO and SVR. OBJECTIVE: To assess the literature related to the use of ICG in guiding the selection of anti-hypertensive medications in individuals with hypertension. DESIGN: PubMed and Cumulative Index to Nursing and Allied Health Literature databases were searched for pertinent literature. Only English language, primary research reports published between 1990 and 2014 were included. FINDINGS: The literature demonstrated significant reduction of blood pressure among participants who were treated with ICG-guided selection of anti-hypertensive medications when compared to standard treatment. CONCLUSION: Although the research reviewed is not without limitations (e.g., small sample sizes and small effect sizes), individualized pharmacologic treatment of uncontrolled hypertension based on ICG-obtained hemodynamics seems successful in reducing blood pressure. Further research within the Canadian context that addresses the limitations is warranted. PMID- 27356463 TI - A General Method for Constructing Two-Dimensional Layered Mesoporous Mono- and Binary-Transition-Metal Nitride/Graphene as an Ultra-Efficient Support to Enhance Its Catalytic Activity and Durability for Electrocatalytic Application. AB - We constructed a series of two-dimensional (2D) layered mesoporous mono- and binary-transition-metal nitride/graphene nanocomposites (TMN/G, TM = Ti, Cr, W, Mo, TiCr, TiW, and TiMo) via an efficient and versatile nanocasting strategy for the first time. The 2D layered mesoporous TMN/G is constituted of small TMN nanoparticles composited with graphene nanosheets and has a large surface area with high porosity. Through decoration with well-dispersed Pt nanoparticles, 2D layered mesoporous Pt/TMN/G catalysts can be obtained that display excellent catalytic activity and stability for methanol electro-oxidation reactions (MOR) and oxygen reduction reactions (ORR) in both acidic and alkaline media. The 2D layered mesoporous binary-Pt/TMN/G catalysts possess catalytic activity superior to that of mono-Pt/TMN/G, graphene free Pt/TMN, Pt/G, and Pt/C catalysts. Encouragingly, the 2D layered mesoporous Pt/Ti0.5Cr0.5N/G catalyst exhibits the best electrocatalytic performance for both MOR and ORR. The outstanding electrocatalytic performance of the Pt/Ti0.5Cr0.5N/G catalyst is rooted in its large surface area, high porosity, strong interaction among Pt, Ti0.5Cr0.5N, and graphene, an excellent electron transfer property facilitated by N-doped graphene, and the small size of Pt and Ti0.5Cr0.5N nanocrystals. The outstanding catalytic performance provides the 2D layered mesoporous Pt/Ti0.5Cr0.5N/G catalyst with a wide range of application prospects in direct methanol fuel cells in both acidic and alkaline media. The synthetic method may be available for constructing other 2D layered mesoporous metal nitrides, carbides, and phosphides. PMID- 27356465 TI - Engineering the Mechanical Properties of Monolayer Graphene Oxide at the Atomic Level. AB - The mechanical properties of graphene oxide (GO) are of great importance for applications in materials engineering. Previous mechanochemical studies of GO typically focused on the influence of the degree of oxidation on the mechanical behavior. In this study, using density functional-based tight binding simulations, validated using density functional theory simulations, we reveal that the deformation and failure of GO are strongly dependent on the relative concentrations of epoxide (-O-) and hydroxyl (-OH) functional groups. Hydroxyl groups cause GO to behave as a brittle material; by contrast, epoxide groups enhance material ductility through a mechanically driven epoxide-to-ether functional group transformation. Moreover, with increasing epoxide group concentration, the strain to failure and toughness of GO significantly increases without sacrificing material strength and stiffness. These findings demonstrate that GO should be treated as a versatile, tunable material that may be engineered by controlling chemical composition, rather than as a single, archetypical material. PMID- 27356464 TI - Age at introduction of solid foods and feeding difficulties in childhood: findings from the Southampton Women's Survey. AB - This study aimed to determine whether age at introduction of solid foods was associated with feeding difficulties at 3 years of age. The present study was carried out using data from the Southampton Women's Survey (SWS). Women enrolled in the SWS who subsequently became pregnant were followed-up during pregnancy and postpartum, and the offspring have been studied through childhood. Maternal socio demographic and anthropometric data and child anthropometric and feeding data were collected through interviews and self-administered questionnaires. When the children were 3 years of age, mothers/carers rated six potential child feeding difficulty questions on a four-point Likert scale, including one general question and five specific feeding difficulty questions. Age at introduction of solids as a predictor of feeding difficulties was examined in 2389 mother-child pairs, adjusting for child (age last breast fed, sex, gestation) and maternal characteristics (parity, pre-pregnancy BMI, age, education, employment, parenting difficulties, diet quality). The majority of mothers/carers (61 %) reported some feeding difficulties (general feeding difficulty question) at 3 years of age, specifically with their child eating enough food (61 %), eating the right food (66 %) and being choosy with food (74 %). Children who were introduced to solids >=6 months had a lower risk of feeding difficulties (RR 0.73; 95 % CI 0.59, 0.91, P=0.004) than children who were introduced to solids between 4 and 6 months. No other significant associations were found. There were few associations between feeding difficulties in relation to age at introduction of solid foods. However, general feeding difficulties were less common among infants introduced to solid foods >=6 months of age. PMID- 27356466 TI - Identifying the brain regions associated with acute spasticity in patients diagnosed with an ischemic stroke. AB - Spasticity is a common impairment found in patients that have been diagnosed with a stroke. Little is known about the pathophysiology of spasticity at the level of the brain. This retrospective study was performed to identify an association between the area of the brain affected by an ischemic stroke and the presence of acute spasticity. Physical and occupational therapy assessments from all patients (n = 441) that had suffered a stroke and were admitted into a local hospital over a 4-year period were screened for inclusion in this study. Subjects that fit the inclusion criteria were grouped according to the presence (n = 42) or absence (n = 129) of acute spasticity by the Modified Ashworth Scale score given during the hospital admission assessment. Magnetic resonance images from 20 subjects in the spasticity group and 52 from the control group were then compared using lesion density plots and voxel-based lesion-symptom mapping. An association of acute spasticity with the gray matter regions of the insula, basal ganglia, and thalamus was found in this study. White matter tracts including the pontine crossing tract, corticospinal tract, internal capsule, corona radiata, external capsule, and the superior fronto-occipital fasciculus were also found to be significantly associated with acute spasticity. This is the first study to describe an association between a region of the brain affected by an infarct and the presence of acute spasticity. Understanding the regions associated with acute spasticity will aid in understanding the pathophysiology of this musculoskeletal impairment at the level of the brain. PMID- 27356467 TI - Effects of reduced in utero and post-weaning nutrition on milk yield and composition in primiparous beef cows. AB - Development and long-term retention of replacement beef females in a semi-arid environment are of a major concern for extensive livestock producers. Furthermore, the demand of not only producing a thriving, healthy calf, but having sufficient milk to support that first calf is essential. To address this issue, we conducted a 3-year study measuring milk production and milk constituent yields in primiparous beef heifers (n=48; 16/year reared under two different feeding regimens) raising steer calves. Cows received 1.8 or 1.2 kg/day winter supplementation for ~80 day before parturition and their heifer calves were then randomly assigned to heifer development treatments that provided ad libitum (AL) or 80% (less than ad libitum (LAL)) of ad libitum feed post weaning. Heifers developed on the AL treatment also received 1.8 kg/day winter supplementation for life, whereas heifers developed on the LAL treatment received 1.2 kg/day winter supplementation for life. Milk production of primiparous cows was measured with a portable milking machine every other week from days 27 to 125 postpartum. Milk yield for the 125-day lactation period was calculated from area under the lactation curve approximated by trapezoidal summation. The ANOVA model included in utero winter nutrition, post-weaning heifer development treatment, year and their interaction. Heifers subjected to the AL treatment reached peak milk yield ~12.3 day later (P=0.02) than heifers receiving LAL treatment. In addition, an in utero nutrition*post-weaning heifer treatment*year interaction existed (P?0.04) for milk peak yield, average daily milk yield (kg/day) and nutrient composition (protein, lactose, fat, solids non-fat, g/day). These interactions manifest as changes in magnitude and rank across the 3 years of the study. Livestock production in extensive environments is subject to variations in seasonal precipitation patterns and quality and quantity of grazeable forage and these fluctuations have a large impact on milk yield. In summary, the gestational nutritional environment of a heifer's mother may interact with the heifer's nutrient consumption during post-weaning growth and the current year to trigger variation in year-to-year milk production. PMID- 27356468 TI - Donor-Derived Regulatory T Cells Attenuate the Severity of Acute Graft-Versus Host Disease after Cord Blood Transplantation. AB - Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) is a curative therapy for some types of hematological disorders. However, allo-PBSCT is commonly complicated with acute graft-versus-host disease (aGVHD), characterized by host tissues being attacked by the grafted donor lymphocytes due to disparities of human leukocyte antigen (HLA) between the donor and host. By contrast, cord blood transplantation (CBT) is typically associated with low-grade severity of aGVHD, but the underlying mechanisms remain unclear. Donor-derived CD4(+) alloreactive T cells (ATs) are of a specific lymphocyte subset, which can be activated by the recipient's HLA, and play a crucial role in the onset of aGVHD. In the present study, we aimed to explore the difference in the property of CD4(+) ATs between cord blood (CB) and adult peripheral blood (APB). We thus found that CB and APB CD4(+) ATs contained not only effector T cells (Teffs) that execute aGVHD, but also a distinct subset of FoxP3(+) regulatory T cells (Tregs) that may alleviate aGVHD. Importantly, CB CD4(+) ATs contained higher percentage of FoxP3(+) Tregs, compared to APB CD4(+) ATs (P < 0.001), while lower percentage of Teffs (Th1, Th2 and Th17 cells) was detected in CB CD4(+) ATs (P < 0.05, P < 0.001 and P < 0.05, respectively). Our findings suggest that FoxP3(+) Tregs in CB CD4(+) ATs may contribute to attenuating the severity of aGVHD observed after CBT. PMID- 27356470 TI - Trends and advances in the diagnosis and control of paratuberculosis in domestic livestock. AB - Paratuberculosis (pTB) is a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP) in a wide variety of domestic and wild animals. Control of pTB is difficult due to the lack of sensitive, efficacious and cost-effective diagnostics and marker vaccines. Microscopy, culture, and PCR have been used for the screening of MAP infection in animals for quite a long time. Besides, giving variable sensitivity and specificity, these tests have not been considered ideal for large-scale screening of domestic livestock. Serological tests like ELISA easily detects anti-MAP antibodies. However, it cannot differentiate between the vaccinated and infected animals. Nanotechnology-based diagnostic tests are underway to improve the sensitivity and specificity. Newer generation diagnostic tests based on recombinant MAP secretory proteins would open new paradigm for the differentiation between infected and vaccinated animals and for early detection of the infection. Due to higher seroreactivity of secretory proteins vis-a-vis cellular proteins, the secretory proteins may be used as marker vaccine, which may aid in the control of pTB infection in animals. Secretory proteins can be potentially used to develop future diagnostics, surveillance and monitoring of the disease progression in animals and the marker vaccine for the control and eradication of pTB. PMID- 27356469 TI - Systemic desensitization through TRPA1 channels by capsazepine and mustard oil - a novel strategy against inflammation and pain. AB - We demonstrate a novel dual strategy against inflammation and pain through body wide desensitization of nociceptors via TRPA1. Attenuation of experimental colitis by capsazepine (CPZ) has long been attributed to its antagonistic action on TRPV1 and associated inhibition of neurogenic inflammation. In contrast, we found that CPZ exerts its anti-inflammatory effects via profound desensitization of TRPA1. Micromolar CPZ induced calcium influx in isolated dorsal root ganglion (DRG) neurons from wild-type (WT) but not TRPA1-deficient mice. CPZ-induced calcium transients in human TRPA1-expressing HEK293t cells were blocked by the selective TRPA1 antagonists HC 030031 and A967079 and involved three cysteine residues in the N-terminal domain. Intriguingly, both colonic enemas and drinking water with CPZ led to profound systemic hypoalgesia in WT and TRPV1(-/-) but not TRPA1(-/-) mice. These findings may guide the development of a novel class of disease-modifying drugs with anti-inflammatory and anti-nociceptive effects. PMID- 27356473 TI - [Expert consensus document of the diagnosis and treatment of pregnancy with heart disease]. PMID- 27356471 TI - Increased circulating concentrations of mesencephalic astrocyte-derived neurotrophic factor in children with type 1 diabetes. AB - Mesencephalic astrocyte-derived neurotrophic factor (MANF) was recently shown to be essential for the survival and proliferation of pancreatic beta-cells in mice, where deletion of MANF resulted in diabetes. The current study aimed at determining whether the concentration of circulating MANF is associated with the clinical manifestation of human type 1 diabetes (T1D). MANF expression in T1D or MANF levels in serum have not been previously studied. We developed an enzyme linked immunosorbent assay (ELISA) for MANF and measured serum MANF concentrations from 186 newly diagnosed children and adolescents and 20 adults with longer-term T1D alongside with age-matched controls. In healthy controls the mean serum MANF concentration was 7.0 ng/ml. High MANF concentrations were found in children 1-9 years of age close to the diagnosis of T1D. The increased MANF concentrations were not associated with diabetes-predictive autoantibodies and autoantibodies against MANF were extremely rare. Patients with conspicuously high MANF serum concentrations had lower C-peptide levels compared to patients with moderate MANF concentrations. Our data indicate that increased MANF concentrations in serum are associated with the clinical manifestation of T1D in children, but the exact mechanism behind the increase remains elusive. PMID- 27356472 TI - Transcriptome comparison reveals a genetic network regulating the lower temperature limit in fish. AB - Transcriptional plasticity is a major driver of phenotypic differences between species. The lower temperature limit (LTL), namely the lower end of survival temperature, is an important trait delimiting the geographical distribution of a species, however, the genetic mechanisms are poorly understood. We investigated the inter-species transcriptional diversification in cold responses between zebrafish Danio rerio and tilapia Oreochromis niloticus, which were reared at a common temperature (28 degrees C) but have distinct LTLs. We identified significant expressional divergence between the two species in the orthologous genes from gills when the temperature cooled to the LTL of tilapia (8 degrees C). Five KEGG pathways were found sequentially over-represented in the zebrafish/tilapia divergently expressed genes in the duration (12 hour) of 8 degrees C exposure, forming a signaling cascade from metabolic regulation to apoptosis via FoxO signaling. Consistently, we found differential progression of apoptosis in the gills of the two species in which zebrafish manifested a delayed and milder apoptotic phenotype than tilapia, corresponding with a lower LTL of zebrafish. We identified diverged expression in 25 apoptosis-related transcription factors between the two species which forms an interacting network with diverged factors involving the FoxO signaling and metabolic regulation. We propose a genetic network which regulates LTL in fishes. PMID- 27356474 TI - [Incidence of singleton macrosomia in Beijing and its risk factors]. AB - OBJECTIVE: To evaluate the prevalence of macrosomia in Beijing in 2013 and identify its risk factors. METHODS: Retrospective six months analysis of 14 188 full-term singleton pregnant women from 15 hospitals with different levels in Beijing in 2013. Each participant's demographic data and medical information were collected individually by questionnaires. Multiple logistic regression analysis was used to examine the associations between variables and the risk of macrosomia. RESULTS: (1)The total prevalence of macrosomia was 7.069% (1 003/14 188) in Beijing in 2013. (2)The prevalence varied between the 15 hospitals, the lowest was 5.36% (89/1 659), while the highest reached 8.80%(46/523). Furthermore, the incidence of macrosomia was 1.284 times (95% CI: 1.114- 1.480, P=0.001) higher in the second graded hospitals than that in the tertiary hospitals. (3) Multiple logistic regression analyses showed that risk factors for macrosomia were maternal height>=160 cm (adjusted OR=1.875, 95% CI: 1.559- 2.256), pre-pregnant body mass index (p-BMI) >=24.0 kg/m(2) (24.0- 27.9 kg/m(2): adjusted OR=1.696, 95% CI: 1.426- 2.018; p-BMI>=28.0 kg/m(2): adjusted OR=2.393, 95% CI: 1.831- 3.127), gestational weight gain (GWG) >=15.9 kg (adjusted OR=2.462, 95% CI: 2.125- 2.853), gravidity>1 (adjusted OR=1.408, 95% CI: 1.224- 1.620), gestational weeks>=40 (adjusted OR=2.007, 95%CI: 1.745-2.308) and gestational diabetes mellitus (adjusted OR=1.522, 95%CI: 1.298-1.784). GWG>=15.9 kg, p-BMI>=28.0 kg/m(2) and gestational weeks>=40 were three risk factors that had the strongest associations with macrosomia (all P<0.01). CONCLUSIONS: The prevalence of macrosomia in hospitals with different levels is obvious different. Gestational weeks, p-BMI and GWG are three main controllable risk factors for macrosomia, thus should receive more attentions. PMID- 27356475 TI - [Clinical application value of echocardiography combined with genetic testing in fetal cardiac rhabdomyoma]. AB - OBJECTIVE: To investigate the clinical value of echocardiography combined with genetic testing in the fetal cardiac rhabdomyoma. METHODS: Thirty-three fetal cardiac rhabdomyoma cases diagnosed by fetal echocardiogram in Beijing Anzhen Hospital from Jan. 2011 to Oct. 2015 were enrolled in a retrospective analysis. The results of other examination and pregnancy outcomes of them were followed up, the genetic characteristics of cardiac rhabdomyoma were summarized on the basis of pathology and genetics examination results. RESULTS: The pregnancy outcomes: 24 cases were terminated pregnancy, 4 cases were born and 5 cases were lost. The results of ultrasound, pathology and genetic examination were detailed in 8 cases. Pathological examination: the typical characteristics of cardiac rhabdomyoma were found in the 8 cases with cardiac rhabdomyoma. The tumor tissue was composed of irregular and swelling shape of cardiomyocytes, and the cytoplasm was vacuole like, which was characteristic of " spider like cells" through microscopic observation. The geneticdetection results: 7 cases had tuberous sclerosis complex (TSC) gene mutation, TSC gene abnormalities were not detected in 1 case. Among the 7 cases with TSC gene mutations, 6 cases were with TSC2 gene mutation and the other 1 case was with TSC1 gene mutation. The family gene was investigated in the 5 cases, which including 3 cases of TSC gene mutation in mother passed on to the fetus (1 case with family of three generations of genetic) and 2 cases of spontaneous TSC gene mutation in the fetus. CONCLUSIONS: Prenatal echocardiography combined with genetic detection have important clinical significance, which not only can clear if cardiac rhabdomyomas were associated with TSC, but also can clear the TSC gene mutation source. So as to further guide the perinatal management. PMID- 27356476 TI - [Expression of mRNA and protein of Klotho gene in placental tissue of macrosomia and its relationship with birth weight of neonates]. AB - OBJECTIVE: To explore the the expression of Klotho mRNA and protein in placenta of macrosomia and its relationship with the birth weight of neonates. METHODS: The cases were from November 2014 to March 2015 in Shengjing Hospital of China Medical University, divided into 4 groups: the gestational diabetes with macrosomia group (GM), the gestational diabetes with normal birth weight group (GN), the normal pregnancy with macrosomia group (NM) and the normal pregnancy with normal birth weight group (NN). Klotho mRNA and protein expression in the placenta were detected by immunohistochemistry SP method, real-time fluorescent quantitative PCR and western blot, respectively, and were compared among the 4 groups. RESULTS: (1) Immunohistochemical detection showed the positive rate of Klotho protein was significantly higher in the placenta of GM (93%,28/30) than in the GN (73%,22/30; P<0.05). The positive rate was significantly higher in the placenta of NM (97%,29/30) than in the NN (80%,24/30; P<0.05). (2) Real-time fluorescent quantitative PCR showed the Klotho mRNA expression was significantly higher in the placenta of GM (4.3 +/- 3.1) than in the GN (2.1 +/- 2.4; P<0.05). The Klotho mRNA expression was also significantly higher in the placenta of NM (4.8+/- 3.4) than in the NN (2.6+/- 3.3; P<0.05). (3) Western blot showed the Klotho protein expression was significantly higher in the placenta of GM (1.27+/ 0.90) than in the GN (0.64+/-0.24; P<0.05). It was also significantly higher in the placenta of NM (2.51+/-3.52) than in the NN (0.77+/-0.37; P<0.05). (4) There were no significant differences in the expression of Klotho mRNA and protein between GM and NM, GN and NN (P>0.05). CONCLUSIONS: The up-regulation of Klotho gene may be associated with macrosomia. The relationship is not affected by the complication of gestational diabetes. PMID- 27356477 TI - [A prospective study on the effects of levonorgestrel-releasing intrauterine system for adenomyosis with menorrhagia]. AB - OBJECTIVE: To investigate treatment effects of levonorgestrel-releasing intrauterine system (LNG-IUS) for adenomyosis with menorrhea in a prospective study. METHODS: From December 2006 to December 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in outpatient or inpatient clinics of Peking Union Medical College Hospital were given the treatment of LNG IUS. Before and after placement of LNG-IUS, all the patients' parameters were recorded prospectively, including scores of menstruation blood loss, carrying status of IUS, symptoms and scores of dysmenorrhea, biochemical indicators, physical parameters, menstruation patterns and adverse effects. Changes of pictorial chart scores of menstruation and distribution of anemia during follow up were analyzed. RESULTS: Totally 1 100 women meets inclusion criteria, among which 618 cases (56.18%, 618/1 100) had severe menorrhea, with median follow-up period of 28 months (range 1- 60 months), and accumulative carrying rate of 66% at 60 months follow-up. After placement of LNG-IUS, compared with baselines, pictorial chart scores and ratio of menorrhea had decreased significantly (all P<0.01), the scroes of menstruation were 157+/-34, 94+/-35, 70+/-33, 67+/-18, 67+/-20, 65+/-19, 66+/-19, 65+/-21 at 0, 3, 6, 12, 24, 36, 48 and 60 months respectively. During 24 months after placement of LNG-IUS, pictorial chart scores and distribution of anemia had improved significantly compared with preceding period (all P<0.01). We found no dependent factors predicting improvement of pictorial chart scores of menorrhea, which was neither relevant with simultaneous changes of menstruation patterns nor adverse effects (all P>0.05). CONCLUSIONS: LNG-IUS is effective for adenomyosis of menorrhea. Improvement of menstruation blood loss is independent on patients characters, menstruation patterns or adverse effects. PMID- 27356478 TI - [Value of pudendal nerve stimulation for predicting the stress urinary incontinence following pelvic prolapse surgery]. AB - OBJECTIVE: To seek the predictive value of pudendal nerve function that need preventive anti-incontinence surgery at the same time following pelvic prolapse surgery in severe pelvic organ prolapse (POP) patients. METHODS: Seventy women completed this study from January 2014 to June 2015 in Fuzhou General Hospital of Nanjing Military Command, dividing into four groups: POP with or without coexisting occult stress urinary incontinence (OSUI) in preoperation, women with persistent stress urinary incontinence (SUI) in postoperation, women without SUI in postoperation. The pudendal nerve function in preoperation was measured by using Solar Urodynamic Neuro Module, including pudendal nerve terminal motor latency (PNTML), and amplitude. RESULTS: There were statistical significance on bilateral PNTML between POP coexisting OSUI group and only severe POP group [(2.62+/-0.23) versus (2.40+/-0.26) ms in right of PNTML, (2.55+/- 0.21) versus (2.37 +/-0.30) ms in left of PNTML; all P<0.05], but no statistical significance on bilateral amplitude (P>0.05). Compared de novo SUI group with POP group in postoperation, de novo SUI group's right of PNTML was significantly increased [(2.74+/-0.16) versus (2.47+/-0.26) ms; P< 0.05]; and the right of PNTML was extending 2.5 standard deviation at least compared with the health's [(2.10+/ 0.20) ms]. CONCLUSIONS: The PNTML of pudendal nerve of POP coexisting OSUI is severe than only severe POP, the velocity of nerve conduction is slowing, and PNTML extension has a predictive value for postoperative urinary incontinence. When the right of PNTML of preoperative POP increased by at least 2.5 standard deviations than health's, the risk of SUI postoperative strongly increased, and a anti-incontinence surgery at the same time following pelvic prolapse surgery should be adviced. PMID- 27356479 TI - [Differential expression of microRNA in eutopic endometrium tissue during implantation window for patients with endometriosis related infertility]. AB - OBJECTIVE: To predict the genes that affect endometrial receptivity through the differential expression of microRNA (miRNA) in eutopic endometrial tissues during implantation window in patients with endometriosis infertility. METHODS: Among infertile patients that received treatments at the Center for Reproductive Medicine, Peking University Third Hospital between May and December 2013, patients with endometriosis infertility were selected as endometriosis group (among the selected 17 cases, there were 6 cases with follicular phase endometrium and 11 cases with implantation window phase endometrium), and patients with tubal factor infertility were selected as control group (among the selected 19 cases, there were 7 cases with follicular phase endometrium and 12 cases with implantation window phase endometrium). (1)Implantation window phase endometrium was selected from 3 cases in each group. Using miRNA and mRNA joint gene sequencing and database for forecast results, as well as using the negative regulatory relationship between miRNA and mRNA, the intersection of target gene that negatively correlates with miRNA expression were obtained. The co-expression network of miRNA-mRNA wae constructed. Combined with the genes associated with endometrial receptivity found through bioinformatics method, the miRNA with core regulatory functionwas found. (2) Expand sample size to 14 cases for endometriosis group and 16 cases for control group.Reverse transcription (RT)-PCR technique was utilized to detect the expression of miR- 142- 5p, miR- 146a- 5p and miR- 543 in endometrial tissues, and verify miRNA microarray results. RESULTS: (1) miRNA and mRNA microarray screening results showed that, among the endometrial tissues of patients with endometriosis infertility and with implantation window phase, 6 differentially expressed miRNA were indentified, among which miR-142-5p, miR-146a-5p, miR-1281, miR-940, miR-4634 showed significantly enhanced expression and miR- 543 showed significantly inhibited expression. Sixty- three differentially expressed mRNA were indentified, among which 58 mRNA such as CADM1, IL-10RA, ITGAL and LPAR5 had significantly enhanced expression. Five mRNA such as HLA- DRB1,3,4,5 and SOHLH2 showed significantly inhibited expression. Thirty- six taget genes were found in consideration of negatively correlated miRNA expression with the genes, miRNA-mRNA co-expression network were constructed. The miR-543 was found at the core of the network. Targetscan and other database predicted that miR-142-5p, miR- 146a- 5p and miR- 543 could act on various types of endometrial receptivity molecular corresponding marker genes such as HOX10, ITGAV, ITGB3, OPN, LIF, ESR, PGR, CDH1 and MMP. (2) RT- PCR test showed that the average levels of expression of miR-142-5p and miR 146a-5p in implantation window phase endometrium in endometriosis group were 8.3+/-10.6 and 1.9+/-0.8 respectively; the average levels of that in control group were 1.1+/-0.6 and 0.9+/-0.4, respectively. The difference was statistically significant (P=0.027, P=0.015), and was consistent with results from miRNA microarray test. The expression of miR-543 in tissues of follicular phase endometrium in endometriosis group (2.3+/-1.0) was significantly higher than that in control group (1.0 +/- 0.4), and the difference was statistically significant (P=0.008). However, when comparing the expression of miR-543 implantation window phase endometrium in endometriosis group (1.2+/-0.6) with that in control group (1.5+/-1.0), the difference was not statistical significant (P=0.890). CONCLUSIONS: There are multiple differential expressions of miRNA in the implantation window phase endometrium tissues of endometriosis infertility patients, among which miR-142-5p and miR-146a-5p show significantly enhanced expression and may affect embryo implantation by acting on a variety of endometrial receptivity marker molecules. The expression of miR- 543 in implantation window phase endometrium of endometriosis infertility patients is lower than that in the follicular phase, forewarned changes in the pattern of cyclic variation of miR-543, and may be the reason for affecting endometrial receptivity. PMID- 27356480 TI - [A retrospective study on the outcomes of the oncology, fertility and pregnancy in patients with early-stage cervical cancer after undergoing the fertility sparing treatments]. AB - OBJECTIVE: To explore the outcomes of the oncology, the fertility and pregnancy on patients with early-stage cervical cancer after undergoing fertility-sparing treatments, and to investigate its value on clinical treatment. METHODS: A total of 29 patients with cervical cancer (stage Ia2-Ib1) who had undergone the fertility- sparing treatments in Renji Hospital, School of Medicine, Shanghai Jiaotong University from February 2010 to September 2015 were analyzed retrospectively. Surgical procedures included transvaginal cervical cold knife conization (CKC) + laparoscopic pelvic lymphadenectomy (PLD) or total laparoscopic uterine cervix extensive resection (RT; contains PLD); 48 patients with early cervical cancer under going laparoscopic uterine extensive resection (RH; contains PLD) by the same group of physicians in the same period were chosen as the control group. The perioperative related indicators, postoperative specimen examination, pregnancies after surgery and postoperative tumor follow- up results were retrospectively analyzed and compared between the two groups. RESULTS: (1) Among these 29 patients in the study group, 26 cases were underwent the fertility-sparing surgery quick frozen pathological examinations were positive in 3 cases, which underwent total laparoscopic RT eventually. (2) The perioperative related indicators: compared with the study group and the control group, the operation time [(182+/-21), (147+/-24) minutes, respectively] has significant difference (t=6.563, P<0.01). There were no significant difference (P> 0.05) in intra-operative blood loss [(102+/-26), (99+/-34) ml], postoperative aerofluxus time [(1.3+/-0.4), (1.1+/-0.9) days], the average length of hospital stay [(11.2+/-2.1), (10.6+/-3.5) days], rate of urine retention [10%(3/29), 10%(5/48)] and rate of postoperative infection [3% (1/29), 2%(1/48)]. (3)Postoperative specimen examination: compared with the study group and the control group, there were no significant difference (P>0.05) innumber of removed lymphatic nodes (23.4+/-4.1, 22.8+/-3.9), length of cardinal ligament [(2.9+/ 0.5), (3.0+/-0.6) cm], lengthof uterosacral ligament [(2.6+/-0.7), (2.8+/-0.4) cm], length of removed vaginal [(3.4+/-0.3), (3.5+/-0.3) cm]. (4) Pregnancies after surgery and postoperative tumor follow-up results: in the study group, only 14 patients had fertility requirement after treatments. Pregnancies occurred in 5 women (5/14), which included1 case of full-term labor, 1 case of preterm labor, and 3 cases of spontaneous abortion. The Average follow-up time in postoperative patients of the study group and control group was 29.4, and 30.2 months respectively. In follow- up period, compare with study group and the control group, there was no significant difference (chi(2)=0.004, P> 0.05) in the recurrence rate [4% (1/26), 4% (2/48)]. CONCLUSION: Fertility-sparing surgery of early-stage cervical cancer is safe but the outcome of the fertility and pregnancy is still need toimprove. PMID- 27356481 TI - [Expression of Jagged1 mRNA in human epithelial ovarian carcinoma tissues and effect of RNA interference of Jagged1 on growth of xenograft in nude mice]. AB - OBJECTIVE: To investigate the expression of Jagged1 in human epithelial ovarian carcinoma tissues and the effect of Jagged1 on growth of xenograft in nude mice. METHODS: (1) Forty-eight cases of ovarian cancer and 30 cases of patients with benign epithelial ovarian tumor in the Henan Province Xinxiang Central Hospital during Feb. 2011 to Mar. 2014 were enrolled in this study. The mRNA expression of Jagged1, Notch1 and the downstream target genes Hes1, Hey1 were analyzed by using realtime PCR method. (2) The ovarian cancer xenograft models in nude mice were constructed by injecting SKOV3 cells in axillary subcutaneouswere. The nude mice were randomly divided into Jagged1 interference group, blank plasmid group and control group. Each group had 10 mice. They were transfected with pcDNA3.1(+) siRNA-Jagged1, blank plasmid pDC3.1 and phosphate buffer, respectively. The tumor volumes and tumor masses were measured 14 days after transfection and the inhibition rate was calculated. The relative mRNA expression of Jagged1, Notch1, Hes1 and Hey1 in xenograft tissues after transfection in each group was detected by using realtime PCR technique and the relative protein expression of Jagged1, Notch1, Hes1 and Hey1 in xenograft tissues was detected by utilizing western blot method. RESULTS: (1) The relative mRNA expression of Jagged1, Notch1, Hes1 and Hey1 in ovarian cancer tissues were higher than benign ovarian tumor tissues, the differences were statistically significant (P<0.01). (2) The tumor volume was (491+/- 68) mm(3) and tumor mass was (2.6+/-0.4) g in Jagged1 interference group, which were significantly lower than that in the blank plasmid group [(842+/-88) mm(3) and (4.4+/-0.8) g, respectively] and that in the control group [(851+/-90) mm(3) and (4.5+/-0.9) g, respectively; P<0.05], the tumor inhibition rate was 42.2% in Jagged1 interference group, which was significantly higher than that in the blank plasmid group and that in the control group (2.2% and 0, respectively), the differences were statistically significant (P<0.05). The relative mRNA and protein expression of Jagged1, Hes1 and Hey1 in xenograft tissues of nude micein Jagged1 interference group were lower than that in the other two groups, the differences were statistically significant (P<0.05). There were no differences of relative mRNA and protein expression of Notch1 in xenograft tissues of nude mice among the three groups (P>0.05). CONCLUSIONS: Jagged1 is highly expressed in epithelial ovarian carcinoma. Jagged1 gene interference in xenograft tumor can inhibit ovarian cancer cell growth and improve tumor suppressor rate, which probably play roles by inhibiting Notch1 signaling pathway. PMID- 27356482 TI - Chronic l-citrulline supplementation improves cardiac sympathovagal balance in obese postmenopausal women: A preliminary report. AB - The present study evaluated the impact of chronic l-citrulline (L-cit) supplementation on resting heart rate variability (HRV) and blood pressure (BP) in obese postmenopausal women. Participants were randomly assign to either an L cit group (n=12) or a control group (n=11). HRV and BP were measured before and after 8weeks. There were significant decreases (P<0.05) in nLF (sympathetic activity), LnLF/LnHF (sympathovagal balance), and BP as well as a significant increase (P<0.05) in nHF (vagal tone) following L-cit compared with no changes after control. Our findings indicate that L-cit supplementation improves sympathovagal balance in obese postmenopausal women. PMID- 27356483 TI - Responsive Guest Encapsulation of Dynamic Conjugated Microporous Polymers. AB - The host-guest complexes of conjugated microporous polymers encapsulating C60 and dye molecules have been investigated systematically. The orientation of guest molecules inside the cavities, have different terms: inside the open cavities of the polymer, or inside the cavities formed by packing different polymers. The host backbone shows responsive dynamic behavior in order to accommodate the size and shape of incoming guest molecule or guest aggregates. Simulations show that the host-guest binding of conjugated polymers is stronger than that of non conjugated polymers. This detailed study could provide a clear picture for the host-guest interaction for dynamic conjugated microporous polymers. The mechanism obtained could guide designing new conjugated microporous polymers. PMID- 27356484 TI - Synthesis and structural characterization of anion complexes with azacalix[2]dipyrrolylmethane: effect of anion charge on the conformation of the macrocycle. AB - Tetrahomodiazacalix[2]dipyrrolylmethane 1, [-CH2(C4H3N)CR2(C4H3N)CH2N(Me)-]2 an expanded version of the calix[4]pyrrole system, has the tendency to change its ring conformation (1,3-alternate) upon anion binding analogous to calix[4]pyrrole. However, owing to its tertiary amine nitrogen atoms in the ring, it can be protonated and becomes a powerful cationic receptor for anions, besides its inherent hydrogen bonding features. Macrocycle 1 binds with a series of monoanions BF4(-), Cl(-), PhCOO(-) and ClO4(-), and their X-ray structures showed that the ring conformation constitutes the 1,2-alternate form. Upon binding with dianions SO4(2-), CrO4(2-), SiF6(2-) and S2O3(2-), the ring conformation changes to the cone conformation. The intermediate partial cone conformation results for complexes with NO3(-) and Cr2O7(2-) ions. The change in the orientation of the pyrrole NH groups depending on the charge of the anion demonstrates the flexibility of the macrocycle and the dicationic macrocycle stabilizes the anions via both hydrogen bonding and electrostatic interactions. PMID- 27356485 TI - Highly selective plasma-activated copper catalysts for carbon dioxide reduction to ethylene. AB - There is an urgent need to develop technologies that use renewable energy to convert waste products such as carbon dioxide into hydrocarbon fuels. Carbon dioxide can be electrochemically reduced to hydrocarbons over copper catalysts, although higher efficiency is required. We have developed oxidized copper catalysts displaying lower overpotentials for carbon dioxide electroreduction and record selectivity towards ethylene (60%) through facile and tunable plasma treatments. Herein we provide insight into the improved performance of these catalysts by combining electrochemical measurements with microscopic and spectroscopic characterization techniques. Operando X-ray absorption spectroscopy and cross-sectional scanning transmission electron microscopy show that copper oxides are surprisingly resistant to reduction and copper(+) species remain on the surface during the reaction. Our results demonstrate that the roughness of oxide-derived copper catalysts plays only a partial role in determining the catalytic performance, while the presence of copper(+) is key for lowering the onset potential and enhancing ethylene selectivity. PMID- 27356487 TI - MnO nanoparticles embedded in a carbon matrix as high performance lithium-ion battery anodes: preparation, microstructure and electrochemistry. AB - Nano-sized MnO intimately embedded in a porous carbon matrix has been synthesized by a facile method in which the manganese-salts/glycerol sol was used as the precursor. The glycerol plays roles of the chelating agent, the carbon source and the solvent. The X-ray diffraction (XRD) and Raman results indicate that the carbon layer may have an obvious effect on the microstructure of MnO. The first principles density functional theory (DFT) calculations further reveal a considerable charge transfer from MnO to the carbon, leading to a decrease of lattice parameters of MnO and the bond length of Mn-O in the MnO/C composite. The modified microstructure could improve electrochemical performance and meanwhile may explain the phenomenon of exceeding the theoretical capacity. The prepared MnO/C nanocomposite as an anode material displays superior Li-battery performance with a large reversible capacity, excellent cyclic performance and good rate capability. PMID- 27356486 TI - Combined therapy for resistant vitiligo lesions: NB-UVB, microneedling, and topical latanoprost, showed no enhanced efficacy compared to topical latanoprost and NB-UVB. AB - Vitiligo is depigmenting disorder of the skin and mucous membranes but despite various therapeutic options, complete and satisfactory treatment of vitiligo still remains a challenge. Therapeutic success also varies depending on the localization of lesions; hands and bony prominents are considered to be resistant to treatment. We investigated feasibility of treating resistant bilateral symmetrical vitiligo vulgaris and acrofacialis lesions with combination of narrowband UVB and topical prostaglandins (0.005% latanoprost solution) with or without Dermaroller 0.5 mm needle length-assisted microneedling. Frequency of repigmentation onset was generally low (37.8%) and pronounced repigmentation was infrequently seen (26-50% repigmentation in 20.8%, and >50% repigmentation in only 8.8% of repigmenting lesions). Our study, however, showed that latanoprost can be used in combination with NB-UVB phototherapy to induce repigmentation in some vitiligo lesions in resistant-to-treatment location, while addition of skin microneedling seems not to improve the treatment outcome and possibly needs modification. PMID- 27356488 TI - Comparison of TR BandTM and VasoStatTM Hemostasis Devices following Transpedal Catheterization for Lower Extremity Revascularization for Peripheral Arterial Disease. AB - BACKGROUND: Transpedal access is increasingly utilized for peripheral vascular catheterization. There is a paucity of data on the use of radial hemostasis devices as an alternative to manual compression for achievement of hemostasis after this approach. OBJECTIVE: To compare safety and efficacy of two hemostasis devices following transpedal catheterization for lower extremity revascularization for peripheral arterial disease. METHODS: A consecutive cohort of patients with bilateral Rutherford 2-5 disease who underwent transpedal catheterization for peripheral vascular interventions were retrospectively analyzed. In each patient, retrograde tibial artery access was obtained, a 4 French sheath was placed, and all revascularization was performed via tibial access. In all patients, a TR BandTM (Terumo Medical, n = 215) and/or VasoStatTM (Forge Medical, n = 99) were used to apply puncture site compression, following removal of the tibial sheath until hemostasis was achieved. Safety and efficacy of each device was compared. RESULTS: Puncture site hemostasis was achieved in all patients within 2 hours of sheath removal facilitating early discharge. Two access site pseudoaneurysms occurred within 30 days of revascularization, one of which followed TR BandTM placement and the other following VasoStatTM placement (P = 0.53). Each patient was successfully treated with ultrasound-guided thrombin injection. Loss of access site patency by duplex ultrasound occurred in 2 patients following the TR BandTM and a single patient following the VasoStatTM (P = 1.0). CONCLUSION: Both the TR BandTM and the VasoStatTM were effective in achieving hemostasis following transpedal catheterization with low rates of complications. PMID- 27356490 TI - Validation of new renal staging system in AL amyloidosis treated with high dose melphalan and stem cell transplantation. PMID- 27356489 TI - Divergent Evolutionary Pattern of Sugar Transporter Genes is Associated with the Difference in Sugar Accumulation between Grasses and Eudicots. AB - Sugars play a variety of roles in plants, and their accumulation in seeds and/or surrounding pericarp tissues is distinctly different between grasses and eudicots. However, little is known about the evolutionary pattern of genes involved in sugar accumulation in these two major groups of flowering plants. Here, we compared evolutionary rates, gene duplication, and selective patterns of genes involved in sugar metabolism and transport between grasses and eudicots using six grass species and seven eudicot species as materials. Overall, sugar transporter genes exhibit divergent evolutionary patterns, whereas, sugar metabolism genes showing similar evolutionary pattern between monocots and eudicots. Sugar transporter genes have higher frequencies of recent duplication in eudicots than in grasses and their patterns of evolutionary rate are different. Evidence for divergent selection of these two groups of flowering plants is also observed in sugar transporter genes, wherein, these genes have undergone positive selection in eudicots, but not in grasses. Taken together, these findings suggest that sugar transporter genes rather than sugar metabolism genes play important roles in sugar accumulation in plants, and that divergent evolutionary patterns of sugar transporter genes are associated with the difference of sugar accumulation in storage tissues of grasses and eudicots. PMID- 27356491 TI - Targeting Transforming Growth Factor-Beta1 (TGF-beta1) Inhibits Tumorigenesis of Anaplastic Thyroid Carcinoma Cells Through ERK1/2-NFkappakB-PUMA Signaling. AB - BACKGROUND The transforming growth factor-beta (TGF-beta) signaling pathway plays a critical role in promoting tumor growth. TGF-beta1was found to be overexpressed in anaplastic thyroid cancer (ATC). We therefore tested our hypothesis that targeting TGF-beta1 inhibits tumorigenesis of ATC cells. MATERIAL AND METHODS Effects of TGF-beta1 stimulation or TGF-beta1 inhibition by small interfering RNA (TGF-beta1siRNA) on proliferation, colony formation, and apoptosis in 8505C cells in vitro was detected using siRNAs and inhibitors to examine the TGF-beta1 signaling pathway. A subcutaneously implanted tumor model of 8505C cells in nude mice was used to assess the effects of TGF-beta1 inhibition on tumorigenesis development. RESULTS TGF-beta1siRNAs decreased proliferation and colony formation, and increased apoptosis in 8505C cells in vitro and inhibited tumor growth in vivo. TGF-beta1siRNA inhibited phosphorylation ERK1/2 (pERK1/2) and increased p65-dependant PUMA mRNA and protein expression. Knockdown of p65 or PUMA by siRNA reduced TGF-beta1siRNA-induced apoptosis, as well as caspase-3 and PARP activation. Upregulation of p65 or PUMA expression by TGF-beta1siRNA requires pERK1/2 inhibition. TGF-beta1 shRNA inhibited tumor growth in vivo. CONCLUSIONS Therapies targeting the TGF-beta1 pathway may be more effective to prevent primary tumor formation. The ability of this therapy to decrease tumorigenesis may be related to ERK1/2/NF-kappaB/PUMA signaling. PMID- 27356492 TI - Blockade of hypoxia-induced CXCR4 with AMD3100 inhibits production of OA associated catabolic mediators IL-1beta and MMP-13. AB - Binding of the chemokine stromal cell-derived factor-1 (SDF-1) to its receptor C X-C chemokine receptor type 4 (CXCR4) results in receptor activation and the subsequent release of matrix metalloproteinases (MMPs) that contribute to osteoarthritis (OA) cartilage degradation. As hypoxia is a defining feature of the chondrocyte microenvironment, the present study investigated the possible mechanism through which SDF-1 induces cartilage degradation under hypoxic conditions. To do this, OA chondrocyte cultures and patient tissue explants pretreated with the CXCR4 inhibitor, AMD3100 were incubated with SDF-1. It was identified that hypoxic conditions significantly elevated the expression of CXCR4 in osteoarthritic chondrocytes relative to normoxic conditions. Furthermore, SDF 1 elevated MMP-13 mRNA levels and proteinase activity. It also elevated the mRNA and protein levels of runt-related transcription factor 2, and induced the release of glycosaminoglycans and the inflammatory cytokine, interleukin-1beta. By contrast, such changes did not occur to an appreciable degree in cells that were pretreated with AMD3100. The results of the present study demonstrate that even under hypoxic conditions, where CXCR4 expression is significantly elevated in chondrocytes, AMD3100 effectively blocks this receptor and protects chondrocytes from OA-induced catabolism, suggesting that the successful inhibition of CXCR4 may be an effective approach for OA treatment. PMID- 27356493 TI - Projections of cancer incidence and cancer-related deaths in Germany by 2020 and 2030. AB - Past patterns of cancer disease and future changes in the demographic structure have a major influence on the projected incidences of human malignancies. In Germany, nearly a quarter of men and 20% of women die of cancer, and it is estimated that in Germany around 51% men and 43% women will develop cancer during lifetime. Here, we project the cancer incidence case number as well as the number of deaths for the most common cancers in the German population for the years 2020 and 2030. By 2030, prostate cancer will be the most common malignancy, surpassing breast cancer. Lung cancer will rank third most frequent cancer and will remain the most common cause of cancer-related mortality. Additionally, our projections show a marked increase in liver cancer cases with a continuous rise in liver cancer-related deaths. Finally, we project a constant increase in the incidence of pancreatic cancer. Based on our projections, pancreatic cancer will surpass colorectal and breast cancer to rank as the second most common cause of cancer related deaths in Germany by 2030. PMID- 27356494 TI - Availability and dose response of phytophenols from a wheat bran rich cereal product in healthy human volunteers. AB - SCOPE: Phytophenols present in cereals are metabolised to compounds that could be partly responsible for the reduced risk of chronic diseases and all-cause mortality associated with fibre-rich diets. The bioavailability, form and in vivo concentrations of these metabolites require to be established. MATERIALS AND METHODS: Eight healthy volunteers consumed a test meal containing a recommended dose (40 g) and high dose (120 g) of ready-to-eat wheat bran cereal and the systemic and colonic metabolites determined quantitatively by LC-MS. CONCLUSION: Analysis of the systemic metabolomes demonstrated that a wide range of phytophenols were absorbed/excreted (43 metabolites) within 5 h of consumption. These included 16 of the 21 major parent compounds identified in the intervention product and several of these were also found to be significantly increased in the colon. Not all of the metabolites were increased with the higher dose, suggesting some limitation in absorption due to intrinsic factors and/or the food matrix. Many compounds identified (e.g. ferulic acid and major metabolites) exhibit anti inflammatory activity and impact on redox pathways. The combination of postprandial absorption and delivery to the colon, as well as hepatic recycling of the metabolites at these concentrations, is likely to be beneficial to both systemic and gut health. PMID- 27356496 TI - Laser and light therapy for facial warts: a systematic review. AB - Facial verruca plana, or flat warts, are benign skin papillomas caused by human papillomavirus infections. A large portion of cases are refractory to treatment and can cause psychosocial distress in patients. Laser and light modalities offer an alternative therapeutic approach that has not been extensively explored. We systematically reviewed PubMed for studies describing treatment of facial verruca plana using lasers, photodynamic therapy and infrared coagulation. Final inclusion and review of eighteen studies suggests laser and light therapies to have considerable potential in the treatment of this recalcitrant condition. In particular, yttrium aluminium garnet lasers, infrared coagulation and photodynamic therapies have been reported to demonstrate efficacy. Further studies with larger power are required to determine which method should be established as the alternative treatment of choice for recalcitrant facial verrucae. PMID- 27356497 TI - A fast and easy strategy for protein purification using "teabags". AB - Protein purification often involves affinity capture of proteins on stationary resin, alternatively proteins are captured on free flowing resin for subsequent separation from bulk fluid. Both methods require labour and time intensive separation of particulate matter from fluid. We present a method where affinity resin is contained within porous-walled containers, supporting clarification, product recovery, and concentration in a single step with minimal hands-on processing time, without significant investments in equipment. PMID- 27356498 TI - Long-Term Follow-Up of Children with Heart Block Born from Mothers with Systemic Lupus Erythematosus: A Retrospective Study from the Database Pediatric and Congenital Heart Disease in University Hospitals Leuven. AB - BACKGROUND: Children from mothers with systemic lupus erythematosus are frequently born with congenital heart block. This study aimed at evaluating long term outcome because long-term data are scarce. METHODS: In the database of pediatric and congenital heart disease (University Hospitals Leuven), 19 children from systemic lupus erythematosus mothers and who were born with or developed atrioventricular block were identified. All records were reviewed for disease course and outcome. RESULTS: Median follow-up time was 7 years (interquartile ranges [IQR] 4.5-13 years). One child had no heart block at birth and developed only a first-degree block during follow-up. One had a second-degree heart block and developed a complete heart block. Seventeen patients (89%) were born with a complete heart block. Seventeen patients (89%) needed a definitive pacemaker. In all, epicardial leads were used at first implantation. Eighty-two percent received their pacemaker in the first year of life. The first battery had a median lifetime of 5 years (IQR 3.5-5 years), the second 6 years (IQR 4.5-6.3 years), and the third 5 years (IQR 5-6 years). Note that 47% of patients needed a lead replacement due to lead problems. Only one pericardial tamponade after pacemaker implantation. No device or lead infections occurred. The left ventricular systolic function at latest follow-up was normal for all. No patients died. CONCLUSION: In children with heart block born from systemic lupus erythematosus mothers, an early need for pacemaker implantation was documented. The overall battery life was acceptable, but there was a high need for lead replacement. Complication rate was low. Late outcome was good. PMID- 27356500 TI - Cu3 V2 O8 Nanoparticles as Intercalation-Type Anode Material for Lithium-Ion Batteries. AB - Cu3 V2 O8 nanoparticles with particle sizes of 40-50 nm have been prepared by the co-precipitation method. The Cu3 V2 O8 electrode delivers a discharge capacity of 462 mA h g(-1) for the first 10 cycles and then the specific capacity, surprisingly, increases to 773 mA h g(-1) after 50 cycles, possibly as a result of extra lithium interfacial storage through the reversible formation/decomposition of a solid electrolyte interface (SEI) film. In addition, the electrode shows good rate capability with discharge capacities of 218 mA h g( 1) under current densities of 1000 mA g(-1) . Moreover, the lithium storage mechanism for Cu3 V2 O8 nanoparticles is explained on the basis of ex situ X-ray diffraction data and high-resolution transmission electron microscopy analyses at different charge/discharge depths. It was evidenced that Cu3 V2 O8 decomposes into copper metal and Li3 VO4 on being initially discharged to 0.01 V, and the Li3 VO4 is then likely to act as the host for lithium ions in subsequent cycles by means of the intercalation mechanism. Such an "in situ" compositing phenomenon during the electrochemical processes is novel and provides a very useful insight into the design of new anode materials for application in lithium-ion batteries. PMID- 27356499 TI - Oncogenic role of microRNA-20a in human uveal melanoma. AB - As a member of the microRNA (miR)-17-92 cluster, miR-20a has been indicated to be involved in the regulation of the proliferation and invasion of various cancer cells. Previous studies have observed elevated plasma levels of miR-20a in patients with uveal melanoma (UM), compared with normal controls. In the present study, the potential function of miR-20a in UM was investigated. Reverse transcription-quantitative polymerase chain reaction analysis was performed to detect the expression levels of miR-20a in UM cells and tissues. The functions of miR-20a on cell proliferation, migration and invasion were determined in vitro using 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays, respectively. The expression levels of miR-20a were significantly increased in the UM cells and tissues (P<0.05). Subsequently, miR-20a mimics were transfected into UM cells, which led to increases in cell growth, migration and invasion activities. By contrast, miR-20a inhibition markedly suppressed the viability and motility of UM cells in vitro. These data provided convincing evidence that miR-20a may function as an oncogenic miRNA, and may be involved in promoting cell growth and motility in the molecular etiology of UM, suggesting its potential as a candidate therapeutic target for the treatment of patients with UM. PMID- 27356501 TI - Rapid malignant transformation of low-grade astrocytoma in a pregnant woman. AB - We report rapid malignant transformation of diffuse astrocytoma to glioblastoma during pregnancy in a young woman. A 21-year-old woman was found to have a non enhancing right frontal lesion, supposed to be a low-grade astrocytoma according to magnetic resonance imaging (MRI) studied for chronic headache. Due to the absence of clinical symptoms, the patient refused further investigations and delivered a baby and then became pregnant with a second baby. At first, she refused the biopsy because she was afraid, although the size of the lesion on MRI was increasing; however, due to repeated persuasion, she underwent a biopsy during the 4th month of her second gestation, with a result of diffuse astrocytoma (WHO grade II). At 1 month after the second delivery and 6 months after the biopsy, MRI revealed further enlargement of the tumor and a heterogeneous kenhancement effect. A gross tumor removal was carried out, and the tumor was histologically diagnosed as glioblastoma (WHO grade IV). This is the quickest ever malignant transformation of diffuse astrocytoma during pregnancy in the published reports. PMID- 27356502 TI - Utilization of maternal health care services and their determinants in Karnataka State, India. AB - BACKGROUND: Karnataka State continues to have the highest rates of maternal mortality in south India at 144/100,000 live births, but lower than the national estimates of 190-220/100,000 live births. Various barriers exist to timely and appropriate utilization of services during pregnancy, childbirth and postpartum. This study aimed to describe the patterns and determinants of routine and emergency maternal health care utilization in rural Karnataka State, India. METHODS: This study was conducted in Karnataka in 2012-2013. Purposive sampling was used to convene twenty three focus groups and twelve individual interviews with community and health system representatives: Auxiliary Nurse Midwives and Staff Nurses, Accredited Social Health Activists, community leaders, male decision-makers, female decision-makers, women of reproductive age, medical officers, private health care providers, senior health administrators, District health officers, and obstetricians. Local researchers familiar with the setting and language conducted all focus groups and interviews, these researchers were not known to community participants. All discussions were audio recorded, transcribed, and translated to English for analysis. A thematic analysis approach was taken utilizing an a priori thematic framework as well as inductive identification of themes. RESULTS: Most women in the focus groups reported regular antenatal care attendance, for an average of four visits, and more often for high-risk pregnancies. Antenatal care was typically delivered at the periphery by non-specialised providers. Participants reported that sought was care women experienced danger signs of complications. Postpartum care was reportedly rare, and mainly sought for the purpose of neonatal care. Factors that influenced women's care-seeking included their limited autonomy, poor access to and funding for transport for non-emergent conditions, perceived poor quality of health care facilities, and the costs of care. CONCLUSIONS: Rural south Indian communities reported regular use of health care services during pregnancy and for delivery. Uptake of maternity care services was attributed to new government programmes and increased availability of maternity services; nevertheless, some women delayed disclosure of pregnancy and first antenatal visit. Community-based initiatives should be enhanced to encourage early disclosure of pregnancies and to provide the community information regarding the importance of facility-based care. Health facility infrastructure in rural Karnataka should also be enhanced to ensure a consistent power supply and improved cleanliness on the wards. TRIAL REGISTRATION: NCT01911494. PMID- 27356504 TI - Proceedings of The 8th Romanian National HIV/AIDS Congress and The 3rd Central European HIV Forum : Sibiu, Romania. 5-7 May 2016. PMID- 27356503 TI - Mpath maps multi-branching single-cell trajectories revealing progenitor cell progression during development. AB - Single-cell RNA-sequencing offers unprecedented resolution of the continuum of state transition during cell differentiation and development. However, tools for constructing multi-branching cell lineages from single-cell data are limited. Here we present Mpath, an algorithm that derives multi-branching developmental trajectories using neighborhood-based cell state transitions. Applied to mouse conventional dendritic cell (cDC) progenitors, Mpath constructs multi-branching trajectories spanning from macrophage/DC progenitors through common DC progenitor to pre-dendritic cells (preDC). The Mpath-generated trajectories detect a branching event at the preDC stage revealing preDC subsets that are exclusively committed to cDC1 or cDC2 lineages. Reordering cells along cDC development reveals sequential waves of gene regulation and temporal coupling between cell cycle and cDC differentiation. Applied to human myoblasts, Mpath recapitulates the time course of myoblast differentiation and isolates a branch of non-muscle cells involved in the differentiation. Our study shows that Mpath is a useful tool for constructing cell lineages from single-cell data. PMID- 27356505 TI - Influence of culture, residential segregation and socioeconomic development on rural elderly health-related quality of life in Guangxi, China. AB - BACKGROUND: This study aimed to assess ethnic differences in health-related quality of life (HRQoL) among the rural elderly, and to examine the influence of ethnic culture, residential segregation and socioeconomic development on HRQoL. METHODS: A total of 6,511 rural elderly aged 60 years and older from 5,541 households in 116 villages across eight ethnic groups in Guangxi Zhuang Autonomous region were selected and assessed for HRQoL. The EQ-5D index values were calculated based on the Chinese Time Trade-Off values set. The EQ-5D descriptive system scores, visual analogue scale scores, and index values were described by ethnic group. The EQ-5D index was modeled against ethnic culture, residential segregation and socioeconomic development using villages as random effects. RESULTS: The median (IQR) of HRQoL among all the ethnic groups was 0.88 (0.80, 0.96). Pain/discomfort was the most prevalent problem, followed by anxiety/depression. After controlling for sociodemographic characteristics, a significant difference in HRQoL among ethnic groups persisted, but this was not true for residential segregation. CONCLUSION: Social welfare and health policies designed to improve the health of the rural elderly should focus more on older, female, less-educated, Yao minority individuals as well as lower-income households. PMID- 27356507 TI - Where is the ball? Behavioral and neural responses elicited by a magic trick. AB - We present results from two experiments, in which subjects watched continuous videos of a professional magician repeatedly performing a maneuver in which a ball could "magically" appear under a cup. In all cases, subjects were asked to predict whether the ball would appear under the cup or not, while scalp EEG recordings were performed. Both experiments elicited strong and consistent behavioral and neural responses. In the first experiment, we used two blocks of videos with different probabilities of the ball appearing in the cup and found that, first, based on the behavioral responses, the subjects could track this probability change; and second, the different probabilities modulated the neural responses. In the second experiment, we introduced a control condition in which the magician performed the maneuver under the table, out of subjects' view. Comparing the two conditions (i.e., performing the maneuver within or out of the subjects' view), we found that, first, the magic trick dramatically biased the subjects' behavioral responses; and second, the two conditions led to differential neural responses, in spite of the fact that the stimulus triggering the evoked responses (seeing the ball in the cup) was exactly the same. Altogether, our results show how new insights into sensory and cognitive processing can be obtained using adapted magic tricks. Moreover, the approach of analyzing responses to continuous video presentations offers a more ecological setting compared to classic evoked potential paradigms, which are typically based on presenting static images flashed at the center of the screen. PMID- 27356506 TI - Mixed messages: wild female bonobos show high variability in the timing of ovulation in relation to sexual swelling patterns. AB - BACKGROUND: The evolution of primate sexual swellings and their influence on mating strategies have captivated the interest of biologists for over a century. Across the primate order, variability in the timing of ovulation with respect to females' sexual swelling patterns differs greatly. Since sexual swellings typically function as signals of female fecundity, the temporal relation between ovulation and sexual swellings can impact the ability of males to pinpoint ovulation and thereby affect male mating strategies. Here, we used endocrine parameters to detect ovulation and examined the temporal relation between the maximum swelling phase (MSP) and ovulation in wild female bonobos (Pan paniscus). Data were collected at the Luikotale field site, Democratic Republic of Congo, spanning 36 months. Observational data from 13 females were used to characterise female swelling cycles (N = 70). Furthermore, we measured urinary oestrone and pregnanediol using liquid chromatography-tandem mass spectrometry, and used pregnanediol to determine the timing of ovulation in 34 cycles (N = 9 females). RESULTS: We found that the duration of females' MSP was highly variable, ranging from 1 to 31 days. Timing of ovulation varied considerably in relation to the onset of the MSP, resulting in a very low day-specific probability of ovulation and fecundity across female cycles. Ovulation occurred during the MSP in only 52.9 % of the analysed swelling cycles, and females showed regular sexual swelling patterns in N = 8 swelling cycles where ovulation did not occur. These findings reveal that sexual swellings of bonobos are less reliable indicators of ovulation compared to other species of primates. CONCLUSIONS: Female bonobos show unusual variability in the duration of the MSP and in the timing of ovulation relative to the sexual swelling signal. These data are important for understanding the evolution of sexual signals, how they influence male and female mating strategies, and how decoupling visual signals of fecundity from the periovulatory period may affect intersexual conflict. By prolonging the period during which males would need to mate guard females to ascertain paternity, the temporal variability of this signal may constrain mate-guarding efforts by male bonobos. PMID- 27356508 TI - Occurrence, enantiomeric signature and ecotoxicological risk assessment of HCH isomers and DDT metabolites in the sediments of Kabul River, Pakistan. AB - Hexachlorocyclohexane (HCH) isomers and dichlorodiphenyltrichloroethane (DDT) metabolites were analyzed in sediments of three different depths (0-10, 10-20 and 20-30 cm) collected from Kabul River, Pakistan, in February 2014. The occurrence levels, enantiomer fractions and potential ecological risk of these organochlorine pesticides (OCPs) were evaluated. The total concentrations of ?HCHs and ?DDTs in surface sediments ranged from 4.9-23.9 ng g-1 and from 6.4 18.8 ng g-1 (dry weight basis), respectively. The vertical contamination profile of DDTs was found in order of 20-30 cm >10-20 cm >0-10 cm, indicated that the residue levels of DDTs gradually decreased after it was banned. The ratios of beta-HCH/HCHs ranged from 0.04 to 0.73 (69 % of samples below 0.5) suggesting the fresh input of HCHs, while isomeric ratios of alpha-HCH/gamma-HCH (ranged from 0.02 to 7.94), with 76 % of samples less than 3, indicating the cocktail use of technical grade HCH and lindane in the study area. The ratio of (DDE + DDD)/DDTs (ranged from 0.42 to 0.90) indicated long-term biodegradation of parent DDT. The enantiomer of alpha-HCH was generally racemic or close to racemic for most of the samples, with enantiomeric fraction (EF) value <0.5 for some of the samples indicated the preferential biodegradation of (+)-alpha-HCH enantiomer, while for o,p'-DDT the EF values >0.5 indicated the depletion of (-)-o,p'-DDT enantiomer in most of the samples. According to sediment quality guidelines (SQGs), HCH contamination is the main concern for ecotoxicological risk in Kabul River. PMID- 27356510 TI - A rare case of Wiskott-Aldrich Syndrome with normal platelet size: a case report. AB - BACKGROUND: Wiskott-Aldrich syndrome is a rare X-linked disorder characterized by microthrombocytopenia, eczema, and recurrent infections. It is caused by mutations of the WAS gene. Microthrombocytopenia has been regarded as the key criteria in diagnosing this rare condition. However, in this case report, we describe a case of Wiskott-Aldrich syndrome with normal platelet size. CASE PRESENTATION: We report the case of a 9-month-old Malay boy who presented with persistent thrombocytopenia from birth. Serial blood investigations at birth showed he had normal platelet size. His family history revealed two early neonatal deaths in maternal uncles. Spontaneous bleeding was only seen at the age of 3 months. He was initially treated for immune thrombocytopenic purpura and was started on intravenously administered immunoglobulin. His clinical deterioration and poor response to the immunoglobulin raised suspicion for a different underlying pathology. Molecular analysis of the WAS gene revealed a missense mutation in exon 10. His parents refused further interventions and defaulted on subsequent follow-up appointments. CONCLUSIONS: A diagnosis of Wiskott-Aldrich syndrome should be considered in any male infant who presents with early onset thrombocytopenia despite an absence of small platelet size, a characteristic feature of Wiskott-Aldrich syndrome. PMID- 27356509 TI - In vivo genome-wide profiling reveals a tissue-specific role for 5 formylcytosine. AB - BACKGROUND: Genome-wide methylation of cytosine can be modulated in the presence of TET and thymine DNA glycosylase (TDG) enzymes. TET is able to oxidise 5 methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). TDG can excise the oxidative products 5fC and 5caC, initiating base excision repair. These modified bases are stable and detectable in the genome, suggesting that they could have epigenetic functions in their own right. However, functional investigation of the genome-wide distribution of 5fC has been restricted to cell culture-based systems, while its in vivo profile remains unknown. RESULTS: Here, we describe the first analysis of the in vivo genome-wide profile of 5fC across a range of tissues from both wild type and Tdg-deficient E11.5 mouse embryos. Changes in the formylation profile of cytosine upon depletion of TDG suggest TET/TDG-mediated active demethylation occurs preferentially at intron-exon boundaries and reveals a major role for TDG in shaping 5fC distribution at CpG islands. Moreover, we find that active enhancer regions specifically exhibit high levels of 5fC, resulting in characteristic tissue-diagnostic patterns, which suggest a role in embryonic development. CONCLUSIONS: The tissue-specific distribution of 5fC can be regulated by the collective contribution of TET-mediated oxidation and excision by TDG. The in vivo profile of 5fC during embryonic development resembles that of embryonic stem cells, sharing key features including enrichment of 5fC in enhancer and intragenic regions. Additionally, by investigating mouse embryo 5fC profiles in a tissue-specific manner, we identify targeted enrichment at active enhancers involved in tissue development. PMID- 27356511 TI - Large scale analysis of protein stability in OMIM disease related human protein variants. AB - BACKGROUND: Modern genomic techniques allow to associate several Mendelian human diseases to single residue variations in different proteins. Molecular mechanisms explaining the relationship among genotype and phenotype are still under debate. Change of protein stability upon variation appears to assume a particular relevance in annotating whether a single residue substitution can or cannot be associated to a given disease. Thermodynamic properties of human proteins and of their disease related variants are lacking. In the present work, we take advantage of the available three dimensional structure of human proteins for predicting the role of disease related variations on the perturbation of protein stability. RESULTS: We develop INPS3D, a new predictor based on protein structure for computing the effect of single residue variations on protein stability (DeltaDeltaG), scoring at the state-of-the-art (Pearson's correlation value of the regression is equal to 0.72 with mean standard error of 1.15 kcal/mol on a blind test set comprising 351 variations in 60 proteins). We then filter 368 OMIM disease related proteins known with atomic resolution (where the three dimensional structure covers at least 70 % of the sequence) with 4717 disease related single residue variations and 685 polymorphisms without clinical consequence. We find that the effect on protein stability of disease related variations is larger than the effect of polymorphisms: in particular, by setting to |1 kcal/mol| the threshold between perturbing and not perturbing variations of the protein stability, about 44 % of disease related variations and 20 % of polymorphisms are predicted with |DeltaDeltaG| > 1 kcal/mol, respectively. A consistent fraction of OMIM disease related variations is however predicted to promote |DeltaDeltaG| <= 1 kcal/mol and we focus here on detecting features that can be associated to the thermodynamic property of the protein variant. Our analysis reveals that some 47 % of disease related variations promoting |DeltaDeltaG| <= 1 are located in solvent exposed sites of the protein structure. We also find that the increase of the fraction of variations that in proteins are predicted with |DeltaDeltaG| <= 1 kcal/mol, partially relates with the increasing number of the protein interacting partners, corroborating the notion that disease related, non-perturbing variations are likely to impair protein-protein interaction (70 % of the disease causing variations, with high accessible surface are indeed predicted in interacting sites). The set of OMIM surface accessible variations with |DeltaDeltaG| <= 1 kcal/mol and located in interaction sites are 23 % of the total in 161 proteins. Among these, 43 proteins with some 327 disease causing variations are involved in signalling, structural biological processes, development and differentiation. CONCLUSIONS: We compute the effect of disease causing variations on protein stability with INPS3D, a new state-of-the-art tool for predicting the change in DeltaDeltaG value associated to single residue substitution in protein structures. The analysis indicates that OMIM disease related variations in proteins promote a much larger effect on protein stability than polymorphisms non-associated to diseases. Disease related variations with a slight effect on protein stability (|DeltaDeltaG| < 1 kcal/mol) frequently occur at the protein accessible surface suggesting that they are located in protein protein interactions patches in putative human biological functional networks. The hypothesis is corroborated by proving that proteins with many disease related variations that slightly perturb protein stability are on average more connected in the human physical interactome (IntAct) than proteins with variations predicted with |DeltaDeltaG| > 1 kcal/mol. PMID- 27356512 TI - Neurocognitive outcome in tyrosinemia type 1 patients compared to healthy controls. AB - BACKGROUND: Hereditary Tyrosinemia type 1 (HT1) is a rare metabolic disorder caused by a defect in the enzyme Fumarylacetoacetate Hydrolase. Due to this defect, toxic products accumulate which, in turn, cause liver and kidney dysfunction. Treatment with 2-(2-nitro-4-trifluoromethylbenoyl)-1,3 cyclohexanedione (NTBC) and diet has diminished these problems, but recent data indicate that HT1 patients have neurocognitive problems. However, the neuropsychological profile of these patients is unknown. Therefore, this study aimed to investigate this neuropsychological profile by comparing HT1 patients with healthy controls. METHODS: Neurocognitive testing was performed in a heterogeneous group of 19 NTBC and dietary treated HT1 patients (five female, fourteen male; mean age 12.9 +/- 4.8 years; range 7.9-23.6 years) and 19 age and gender matched controls (five female, fourteen male; mean age 13.2 +/- 4.6 years; range 8.1-24.8 years). IQ scores were estimated and all participants performed the Amsterdam Neuropsychological Tasks, measuring executive functions (inhibition, cognitive flexibility and working memory) and social cognition (face recognition and identification of facial emotions). RESULTS: HT1 patients showed poorer estimated IQ, executive functioning (working memory and cognitive flexibility), and social cognition compared to healthy controls. Lower IQ scores in HT1 patients were mostly unrelated to scores on executive function- and social cognition tasks and therefore did not account for group differences in these domains. Further analyses within the HT1 patient group (comparing different groups of patients based on the age at diagnosis and the clinical symptoms at diagnosis) did not reveal any significant results. The duration of NTBC treatment was negatively correlated with IQ. CONCLUSIONS: Despite the heterogeneity of the patient group, these data clearly show that IQ, executive functioning and social cognition are affected in HT1 patients, and that IQ screening is not sufficient for cognitive monitoring of these patients. Further research should focus on the underlying pathophysiological mechanisms of these impairments to consequently try to improve treatment strategies. PMID- 27356513 TI - Hydrogenation of CO2 to Formic Acid with a Highly Active Ruthenium Acriphos Complex in DMSO and DMSO/Water. AB - The novel [Ru(Acriphos)(PPh3 )(Cl)(PhCO2 )] [1; Acriphos=4,5 bis(diphenylphosphino)acridine] is an excellent precatalyst for the hydrogenation of CO2 to give formic acid in dimethyl sulfoxide (DMSO) and DMSO/H2 O without the need for amine bases as co-reagents. Turnover numbers (TONs) of up to 4200 and turnover frequencies (TOFs) of up to 260 h(-1) were achieved, thus rendering 1 one of the most active catalysts for CO2 hydrogenations under additive-free conditions reported to date. The thermodynamic stabilization of the reaction product by the reaction medium, through hydrogen bonds between formic acid and clusters of solvent or water, were rationalized by DFT calculations. The relatively low final concentration of formic acid obtained experimentally under catalytic conditions (0.33 mol L(-1) ) was shown to be limited by product dependent catalyst inhibition rather than thermodynamic limits, and could be overcome by addition of small amounts of acetate buffer, thus leading to a maximum concentration of free formic acid of 1.27 mol L(-1) , which corresponds to optimized values of TON=16*10(3) and TOFavg ~10(3) h(-1) . PMID- 27356514 TI - Mesophilic Lactic Acid Bacteria Diversity Encountered in Brazilian Farms Producing Milk with Particular Interest in Lactococcus lactis Strains. AB - The milk produced in regions with different traditions in Brazil is used for artisanal product production, which is characterized by different sensorial characteristics. This study aimed to identify the bacterial ecosystem of farms located in a traditional dairy region in the state of Minas Gerais and to characterize Lactococcus lactis strains, the species of interest in this study, using a multilocus sequence typing (MLST) protocol and pulsed-field gel electrophoresis (PFGE) technique. Samples were collected from raw milk and dairy environment from six farms. A total of 50 isolates were analyzed using 16S rRNA sequencing and species-specific PCR. Five genera were identified: Lactobacillus, Leuconostoc, Lactococcus, Enterococcus, and Staphylococcus, from ten different species. MLST (with six housekeeping genes) and PFGE (with SmaI endonuclease) were used for the characterization of 20 isolates of Lactococcus lactis from a dairy collection in this study. Both methods revealed a high clonal diversity of strains with a higher discriminatory level for PFGE (15 pulsotypes), compared to MLST (12 ST). This study contributes to the preservation of the Brazilian dairy heritage and provides insights into a part of the LAB population found in raw milk and dairy environment. PMID- 27356516 TI - Responsiveness of the Tampa Scale of Kinesiophobia in Italian subjects with chronic low back pain undergoing motor and cognitive rehabilitation. AB - PURPOSE: The Tampa Scale of Kinesiophobia (TSK) is a commonly used measure for the assessment of kinesiophobia related to spinal diseases. The Italian version showed satisfactory psychometric properties, but its responsiveness has not yet been evaluated. This observational study is aimed at evaluating the responsiveness and minimal important changes (MICs) for the TSK in subjects with chronic low back pain. METHODS: At the beginning and end of an 8-week multidisciplinary rehabilitation programme, 205 patients completed the TSK. After the programme, patients also completed the global perceived effect (GPE) scale, which was divided to produce a dichotomous outcome. Responsiveness was calculated by distribution [effect size (ES); standardised response mean (SRM)] and anchor based methods [receiver-operating characteristics (ROC) curves; correlations between change scores of the TSK and GPE]. ROC curves were also used to compute the best cut-off levels between subjects with a "good" or "poor" outcome (MICs). RESULTS: The ES and the SRM were 1.49 and 1.36, respectively. The ROC analyses revealed a MIC value (AUC; sensitivity; specificity) of 5.5 (0.996; 95; 97). To avoid any dependence on the baseline scores, the MIC value [area under the curve (AUC); sensitivity; and specificity] was computed also based on the percentage of change from the baseline and a value of 18 % (0.998; 97; 98 %) was obtained. The correlation between change scores of the TSK and GPE was high (0.871). CONCLUSIONS: The TSK was sensitive in detecting clinical changes in subjects with chronic low back pain. We recommend taking the MICs provided into account when assessing patients' improvement or planning studies in this clinical context. PMID- 27356515 TI - The Molecular Mechanisms of Vitamin A Deficiency in Multiple Sclerosis. AB - Vitamin A, considered to be an essential nutrient, has important actions in immunological responses and the central nervous system (CNS). Neuroimmunological functions of vitamin A are mediated through its active metabolite, retinoic acid (RA). In the CNS, RA contributes to regeneration and plasticity, while also playing a key role in enhancing tolerance and reducing inflammatory responses by regulating T cell, B cell and dendritic cell populations. However, evidence has indicated lower plasma levels of vitamin A in patients with multiple sclerosis (MS). Vitamin A deficiency leads to dysregulation of immune tolerance and pathogenic immune cell production in this disease. Vitamin A may ameliorate MS pathogenesis through numerous mechanisms including a reduction in inflammatory processes by re-establishing the balance between pathogenic (Th1, Th17, Th9) and immunoprotective cells (Th2, Tregs), modulating B cell and dendritic cell function as well as increasing tolerance of autoimmunity and regeneration in the CNS. Thus, the results from the current review suggest that vitamin A can be considered as a potential treatment in MS disease management. PMID- 27356517 TI - Sagittal spino-pelvic adjustment in severe Lenke 1 hypokyphotic adolescent idiopathic scoliosis patients. AB - PURPOSE: The human standing position requires permanent reciprocal spino-pelvic adjustments to obtain a dynamic and economic posture. This study focuses on a hypokyphotic Lenke 1 adolescent idiopathic scoliosis (AIS) patients cohort and points out their particular lumbo-pelvic adaptive mechanisms to maintain a neutral sagittal balance. METHODS: Preoperative retrospective analysis of prospectively collected data on a monocentric cohort of 455 AIS patients planned for corrective surgery. Radiological low-dose system coupled with a validated clinical routine software allowed to obtain data from eighty-four hypokyphotic [thoracic kyphosis (TK) <20 degrees ] Lenke 1 patients and were separately analyzed. Bilateral Student and one-way ANOVAs were conducted for statistical analysis. RESULTS: Mean Cobb angle was 46.3 degrees (+/-7.2), TK was 11 degrees (+/-7.1), sagittal vertical axis (SVA) was -10.1 mm (+/-30.9), pelvic incidence (PI) was 55.7 degrees (+/-12.9). Fifty percents of patients were posteriorly imbalanced. Among them, patients with a low PI used an anteversion of their pelvis [indicated by a high pelvic tilt (PT) angle] but were not able to increase their lumbar lordosis (LL) to minimize the posterior spinal shift. CONCLUSIONS: Hypokyphotic Lenke 1 AIS patients use lumbo-pelvic compensatory mechanisms to maintain their global balance with a poor effectiveness. Subjects with a low PI have a restricted range of LL adaptation. Attention should be paid during surgical planning not to overcorrect lordosis in the instrumented levels in case of non-selective fusion, that may induce posterior shift of the fusion mass and expose to junctional syndromes and poor functional outcomes in this particular patients. PMID- 27356518 TI - A prospective, longitudinal study of platelet serotonin and plasma brain-derived neurotrophic factor concentrations in major depression: effects of vortioxetine treatment. AB - BACKGROUND: Various antidepressants occupy brain serotonin transporter (SERT), decrease platelet serotonin (5-HT) concentration, and normalize reduced plasma brain-derived neurotrophic factor (BDNF) concentrations in depressed patients. Vortioxetine is a recently introduced antidepressant with a multimodal mechanism of action. In addition to SERT inhibition, vortioxetine acts via different 5-HT receptors. To further elucidate its mechanism of action, we have investigated the effects of vortioxetine on platelet 5-HT and plasma BDNF concentrations in patients with major depression. METHODS: Platelet 5-HT and plasma BDNF concentrations were determined in 44 healthy subjects at baseline and in 44 depressed patients before and after 4 weeks of treatment with vortioxetine (5-15 mg daily). Platelet 5-HT concentration was determined using the ortho phthalaldehyde-enhanced fluorometric method, and plasma BDNF concentration using a commercial enzyme-linked immunosorbent assay (Quantikine ELISA, R&D Systems). RESULTS: At baseline, platelet 5-HT concentrations did not differ between depressed and control subjects, but plasma BDNF values were lower (p = 0.011; omega = 0.80) in depressed patients than in healthy subjects. Vortioxetine treatment significantly (p < 0.0001; omega = 0.80) decreased platelet 5-HT concentration and significantly (p = 0.004; omega = 0.80) increased plasma BDNF concentration in depressed patients compared to their baseline values. Age, gender, and smoking were not significantly associated with platelet 5-HT and plasma BDNF concentrations. CONCLUSION: Despite a novel mechanism of action, vortioxetine shares some common effects with other antidepressants. This study is the first to show that, in addition to clinical improvement, 4 weeks of treatment with vortioxetine (5-15 mg daily), decreased platelet 5-HT and increased plasma BDNF concentrations in depressed patients. PMID- 27356520 TI - Human Cooperation and Its Underlying Mechanisms. AB - Cooperation is a uniquely human behavior and can be observed across cultures. In order to maintain cooperative behavior in society, people are willing to punish deviant behavior on their own expenses and even without any personal benefits. Cooperation has been object of research in several disciplines. Psychologists, economists, sociologists, biologists, and anthropologists have suggested several motives possibly underlying cooperative behavior. In recent years, there has been substantial progress in understanding neural mechanisms enforcing cooperation. Psychological as well as economic theories were tested for their plausibility using neuroscientific methods. For example, paradigms from behavioral economics were adapted to be tested in the magnetic resonance imaging (MRI) scanner. Also, related brain functions were modulated by using transmagnetic brain stimulation (TMS). While cooperative behavior has often been associated with positive emotions, noncooperative behavior was found to be linked to negative emotions. On a neural level, the temporoparietal junction (TPJ), the striatum, and other reward-related brain areas have been shown to be activated by cooperation, whereas noncooperation has mainly been associated with activity in the insula. PMID- 27356519 TI - Benzodiazepine and neuroactive steroid combinations in rats: anxiolytic-like and discriminative stimulus effects. AB - RATIONALE: Benzodiazepines are effective anxiolytics, hypnotics, and anticonvulsants but unwanted side effects, including abuse potential, limit their use. A possible strategy to increase the therapeutic index of this drug class is to combine benzodiazepines with neuroactive steroids. OBJECTIVES: The present study evaluated the extent to which combinations of benzodiazepines (triazolam, clonazepam) and neuroactive steroids (pregnanolone, ganaxolone) induced additive, supra-additive, or infra-additive effects in an elevated zero maze and a drug discrimination procedure in rats. METHODS: Male Sprague-Dawley rats (N = 7/group) were placed into an elevated zero maze apparatus following injections of multiple doses of triazolam and pregnanolone, alone and combined, or clonazepam and ganaxolone, alone and combined. These drugs/drug combinations also were evaluated in rats (N = 8) trained to discriminate triazolam (0.1 mg/kg, i.p.) from vehicle. Drug interactions were evaluated using isobolographic and dose-addition analysis. RESULTS: In the elevated zero maze, all drugs engendered dose-dependent increases in time spent in the open quadrant when administered alone. Triazolam and pregnanolone, as well as clonazepam and ganaxolone combinations produced additive or supra-additive effects depending on the fixed-proportion that was tested. In triazolam discrimination, all drugs engendered dose-dependent increases in triazolam-lever responding. In combination, triazolam and pregnanolone and clonazepam and ganaxolone produced predominantly additive discriminative stimulus effects, except for one fixed proportion of clonazepam and ganaxolone which had supra-additive effects. CONCLUSIONS: Although drug interactions depended on the constituent drugs, the combination tested, and the behavioral endpoint; a combination was identified that would be predicted to result in supra-additive anxiolytic-like effects with predominantly additive discriminative stimulus effects. PMID- 27356521 TI - On the Control of Social Approach-Avoidance Behavior: Neural and Endocrine Mechanisms. AB - The ability to control our automatic action tendencies is crucial for adequate social interactions. Emotional events trigger automatic approach and avoidance tendencies. Although these actions may be generally adaptive, the capacity to override these emotional reactions may be key to flexible behavior during social interaction. The present chapter provides a review of the neuroendocrine mechanisms underlying this ability and their relation to social psychopathologies. Aberrant social behavior, such as observed in social anxiety or psychopathy, is marked by abnormalities in approach-avoidance tendencies and the ability to control them. Key neural regions involved in the regulation of approach-avoidance behavior are the amygdala, widely implicated in automatic emotional processing, and the anterior prefrontal cortex, which exerts control over the amygdala. Hormones, especially testosterone and cortisol, have been shown to affect approach-avoidance behavior and the associated neural mechanisms. The present chapter also discusses ways to directly influence social approach and avoidance behavior and will end with a research agenda to further advance this important research field. Control over approach-avoidance tendencies may serve as an exemplar of emotional action regulation and might have a great value in understanding the underlying mechanisms of the development of affective disorders. PMID- 27356522 TI - The Abuse Potential of Prescription Opioids in Humans-Closing in on the First Century of Research. AB - While opioids are very effective analgesics for treating acute pain, humans have struggled with opiate addiction for millenia. An opium abuse epidemic in the early 1900's led the US government to develop a systematic research infrastructure and scientific plan to produce new compounds with analgesic properties but without abuse liability. This review describes the techniques that were developed for testing in the human laboratory, including empirically derived outcome measures and required elements for human abuse potential assessment. The evaluation and characterization of semi-synthetic and synthetic opioids, including full mu opioid agonists, partial agonists and mixed agonist antagonists, are described across several decades of research. Finally, the prescription opioid epidemic beginning in the 1990's in the US led to a resurgence in abuse potential evaluations, and the application of these methods to the study of novel abuse-deterrent formulations is discussed. PMID- 27356523 TI - Preclinical Effects of Antipsychotic Drugs. AB - Antipsychotic drugs have been the drugs of choice for the treatment of schizophrenia ever since the introduction of chlorpromazine in the early 1950s of the last century. Since then, about 60 different antipsychotics have been introduced. Although pharmacologically these drugs show large differences, in terms of potency, duration of action and selectivity, all antipsychotics appear to reduce the positive symptoms of schizophrenia, while having little or no effect on the negative symptoms or the cognitive deficits. The only apparent exception is clozapine, which is also effective in therapy-resistant patients. On the other hand, antipsychotics induce significant side effects as well, including neurological, behavioural and metabolic side effects. In the present paper, we will discuss the preclinical pharmacology of the current antipsychotic drugs focussing both on the therapeutic and on side effects of these drugs. PMID- 27356524 TI - A Computational/Experimental Assessment of Antitumor Activity of Polymer Nanoassemblies for pH-Controlled Drug Delivery to Primary and Metastatic Tumors. AB - PURPOSE: Polymer nanoassemblies (PNAs) with drug release fine-tuned to occur in acidic tumor regions (pH < 7) while sparing normal tissues (pH = 7.4) were previously shown to hold promise as nanoparticle drug carriers to effectively suppress tumor growth with reduced systemic toxicity. However, therapeutic benefits of pH-controlled drug delivery remain elusive due to complex interactions between the drug carriers, tumor cells with varying drug sensitivity, and the tumor microenvironment. METHODS: We implement a combined computational and experimental approach to evaluate the in vivo antitumor activity of acid-sensitive PNAs controlling drug release in pH 5 ~ 7.4 at different rates [PNA1 (fastest) > PNA2 > PNA3 (slowest)]. RESULTS: Computational simulations projecting the transport, drug release, and antitumor activity of PNAs in primary and metastatic tumor models of colorectal cancer correspond well with experimental observations in vivo. The simulations also reveal that all PNAs could reach peak drug concentrations in tumors at 11 h post injection, while PNAs with slower drug release (PNA2 and PNA3) reduced tumor size more effectively than fast drug releasing PNA1 (24.5 and 20.3 vs 7.5%, respectively, as fraction of untreated control). CONCLUSION: A combined computational/experimental approach may help to evaluate pH-controlled drug delivery targeting aggressive tumors that have substantial acidity. PMID- 27356526 TI - Routine pelvic examinations have no confirmed benefits, US panel concludes. PMID- 27356525 TI - Quantification of Four Efflux Drug Transporters in Liver and Kidney Across Species Using Targeted Quantitative Proteomics by Isotope Dilution NanoLC-MS/MS. AB - PURPOSE: The expression levels of several efflux drug transporters in the liver and kidney were evaluated across species to address potential roles of the transporters in species dependent excretion of drugs and their metabolites. METHODS: Four efflux transporters, namely MDR1/P-gp, BCRP/Bcrp, MRP2/Mrp2 and MRP3/Mrp3 in liver and kidney in three preclinical species and humans were quantified using targeted quantitative proteomics by isotope dilution nanoLC MS/MS. RESULTS: In liver, the level of P-gp was highest in monkey and lowest in rat. The concentration of BCRP/Bcrp was highest in dog followed by monkey. MRP2/Mrp2 level was highest in monkey and rat, whereas MRP3/Mrp3 levels were similar in human, monkey and dog. In the kidney, the concentrations of MDR1/P-gp in human and monkey were roughly 2 to 3-fold higher than in rat and dog. In rat, BCRP/Bcrp concentrations were substantially higher than in any of the other species. MRP2/Mrp2 concentrations were similar across species, whereas expression of MRP3/Mrp3 was highest in rat. CONCLUSION: Overall, the results indicated that the pattern of hepatic and renal expression of the transporters was quite species dependent. This information should be helpful in the estimation of transport mediated drug and metabolites excretion in liver and kidney across species. PMID- 27356527 TI - Missing Iron-Oxidizing Acidophiles Highly Sensitive to Organic Compounds. AB - The genus Acidithiobacillus includes iron-oxidizing lithoautotrophs that thrive in acidic mine environments. Acidithiobacillus ferrooxidans is a representative species and has been extensively studied for its application to the bioleaching of precious metals. In our attempts to cultivate the type strain of A. ferrooxidans (ATCC 23270(T)), repeated transfers to fresh inorganic media resulted in the emergence of cultures with improved growth traits. Strains were isolated from the resultant culture by forming colonies on inorganic silica-gel plates. A representative isolate (strain NU-1) was unable to form colonies on agarose plates and was more sensitive to organics, such as glucose, than the type strain of A. ferrooxidans. Strain NU-1 exhibited superior growth traits in inorganic iron media to those of other iron-oxidizing acidithiobacilli, suggesting its potential for industrial applications. A draft genome of NU-1 uncovered unique features in catabolic enzymes, indicating that this strain is not a mutant of the A. ferrooxidans type strain. Our results indicate that the use of inorganic silica-gel plates facilitates the isolation of as-yet-unexamined iron-oxidizing acidithiobacilli from environmental samples and enrichment cultures. PMID- 27356528 TI - Aldosterone changes after consumption of a sodium-bicarbonated mineral water in humans. A four-way randomized controlled trial. AB - Abnormally high aldosterone levels are associated to hypertension and cardiovascular disease. A sodium-rich mineral water was previously shown to reduce several markers of cardiovascular risk and did not increase blood pressure in healthy adults. We aimed to study the effects of consuming the same mineral water compared to a control water on aldosterone levels, and if the effects vary due to the presence of meal in healthy adults. The design was a four-way randomized controlled crossover 120-min-postprandial trial. Twenty-one healthy men and women participated in the study. Exclusion criteria are diabetes, hypertension, and being a usual consumer of carbonic mineral water. Two different mineral waters, high-sodium and bicarbonate mineral water (BW, sodium, 1 g/L; bicarbonate, 2 g/L) and low-mineral content control water (CW), were consumed with or without a standard meal (500 mL per meal). Statistical analysis was performed by repeated measures ANOVA. The results are as follows: serum sodium did not vary, and serum potassium decreased throughout the assay (p = 0.01) without water influence. Consumption of BW significantly decreased aldosterone levels at 30 (p = 0.046), 60 (p = 0.009), and 120 (p = 0.025) min when consumed alone, and at 120 min (p = 0.019) when consumed with meal, compared to CW. Moreover, the effect of BW on aldosterone levels was significant in women but not in men. In conclusion, consumption of a sodium-bicarbonated mineral water, in presence or absence of meal, induces aldosterone inhibition in healthy women, which is suggested to be a physiological response that protects them against hypertension. This trial is registered at clinicaltrial.gov as NCT01334840. PMID- 27356529 TI - Fine particulate matter potentiates type 2 diabetes development in high-fat diet treated mice: stress response and extracellular to intracellular HSP70 ratio analysis. AB - Exposure to fine particulate matter (PM2.5) air pollution is a risk factor for type 2 diabetes (T2DM). We argue whether the potentiating effect of PM2.5 over the development of T2DM in high-fat diet (HFD)-fed mice would be related to modification in cell stress response, particularly in antioxidant defenses and 70 kDa heat shock proteins (HSP70) status. Male mice were fed standard chow or HFD for 12 weeks and then randomly exposed to daily nasotropic instillation of PM2.5 for additional 12 weeks under the same diet schedule, divided into four groups (n = 14-15 each): Control, PM2.5, HFD, and HFD + PM2.5 were evaluated biometric and metabolic profiles of mice, and cellular stress response (antioxidant defense and HSP70 status) of metabolic tissues. Extracellular to intracellular HSP70 ratio ([eHSP72]/[iHSP70]), viz. H-index, was then calculated. HFD + PM2.5 mice presented a positive correlation between adiposity, increased body weight and glucose intolerance, and increased glucose and triacylglycerol plasma levels. Pancreas exhibited lower iHSP70 expression, accompanied by 3.7-fold increase in the plasma to pancreas [eHSP72]/[iHSP70] ratio. Exposure to PM2.5 markedly potentiated metabolic dysfunction in HFD-treated mice and promoted relevant alteration in cell stress response assessed by [eHSP72]/[iHSP70], a relevant biomarker of chronic low-grade inflammatory state and T2DM risk. PMID- 27356530 TI - Impact of Formulation on the Pharmacokinetics of Dutasteride: Results from Two Phase I Studies. AB - BACKGROUND AND OBJECTIVES: Dutasteride is currently marketed by GlaxoSmithKline (GSK), either as monotherapy or as a fixed-dose combination with tamsulosin. As part of the project to develop the fixed-dose combination product, alternative formulations of dutasteride were prepared by GSK, and their pharmacokinetic properties were investigated. METHODS: Two single-centre, open-label, active comparator, randomised, three-period crossover studies were performed. The first study evaluated the relative bioavailability of dutasteride 0.5 mg soft gelatin capsule (marketed formulation, reference) versus a dutasteride 0.5 mg hard gelatin capsule and a dutasteride 0.5 mg tablet. The second assessed the relative bioavailability of dutasteride 0.5 mg from soft gelatin capsules containing 300 or 100 mg of mono- and diglycerides of caprylic acid/capric acid (MDC8, an emulsifying agent) versus the marketed formulation. RESULTS: In the first study (n = 36), compared with the marketed soft gelatin capsule formulation, the bioavailability (least squares [LS] means ratio) of the tablet formulation was 76 % (90 % CI 0.68-0.84), and that of the hard gelatin capsule was 73 % (90 % CI 0.66-0.82). Peak exposures were also lower for the tablet (73 %; 90 % CI 0.66 0.81) and hard capsule (71 %; 90 % CI 0.64-0.79) relative to the marketed soft gelatin capsule. In the second study (n = 37), compared with the marketed soft gelatin formulation, the bioavailability (LS means ratio) of the 300 mg MDC8 capsule formulation was 95 % (90 % CI 0.88-1.03), and that of the 100 mg MDC8 capsule formulation was 93 % (90 % CI 0.86-1.00). Peak exposures were also lower for the 300 mg MDC8 (90 %; 90 % CI 0.81-0.99) and 100 mg MDC8 (87 %; 90 % CI 0.79 0.96) formulations. CONCLUSIONS: The bioavailability of, and peak exposure to, dutasteride are influenced by the formulation of the administered medication. These studies demonstrate the importance of formulation for obtaining the optimal pharmacokinetic properties of dutasteride. PMID- 27356531 TI - Chiral Ligand-Exchange Chromatography of Pharmaceutical Compounds on Dynamically Coated (Home-Made) Stationary Phases. AB - It is well known for several decades that the two enantiomeric forms of a chiral compound can have very different effects on the human body. For this reason the synthesis or extraction from a natural source of a potential new drug, as well as its marketing, require a careful control of its optical purity. Chromatographic techniques can respond extremely well to this need, both in the analytical and in the preparative field. Among the several methods developed for this purpose, one of the first and of the most effective is the Chiral Ligand-Exchange Chromatography, which is based on the stability difference between the metallic diastereomeric complexes containing one or the other of the two enantiomers to be separated and a suitable chiral selector. This method has been effectively used for resolving racemic mixtures of products of biomedical and/or pharmacological interest, such as alpha - and beta-amino acids either proteinogenic or non proteinogenic, oligopeptides, amino alcohols or beta-blockers. All these substances are linked together by their ability to bind metal ions, the most widely used of which is Cu(II). The chiral selector can be a component of either the mobile or the stationary phase, to which it can be either chemically bonded or dynamically adsorbed. The latter method has several advantages of convenience and, above all, cheapness. The preparation of dynamically-coated chiral stationary phases for Ligand-Exchange Chromatography has produced a large number of applications, the main of which, both in TLC and in HPLC, are reviewed below. PMID- 27356532 TI - Nitric Oxide: A Universal Modulator of Brain Function. AB - BACKGROUND: The pioneering work of Robert F. Furchgott, Luis J. Ignaro and Ferid Murad has led us to investigate whether nitric oxide (NO) is present in the brain, its origin and whether it possesses a functional role in brain structures. This review is mainly an outline of own findings obtained by using the push-pull superfusion technique. METHOD: We have used the push-pull superfusion technique that makes it possible to determine quantitatively endogenous transmitters released from their neurons in the synaptic cleft. In some experiments, a NO sensor was inserted into the pushpull cannula for online determination of NO released in the synaptic cleft together with neurotransmitters. RESULTS: The release rates of endogenous NO are not constant but oscillate according to an ultradian rhythm with an apparent frequency of about 24 min per cycle. Similar rhythmic changes have been found in the release of neurotransmitters in several brain regions, as well as in the EEG delta band. Endogenous NO modulates the release of acetylcholine, glutamate, aspartate, GABA, serotonin, histamine in distinct brain areas. The release of adenosine is also increased by NO suggesting the synchronous release of ATP. Endogenous NO influences various brain functions such as blood pressure regulation and responses to stress. Recordings of evoked potentials revealed that NO plays a crucial role in the integration of afferent signals. Furthermore, NO in involved in amphetamine-induced neurotoxicity. CONCLUSION: The multifarious influences of endogenous NO on central neuronal activity, brain functions and integration of afferent signals underpin its universal modulatory role in the brain. PMID- 27356533 TI - Recent Advances on Nitric Oxide in the Upper Airways. AB - Exhaled nitric oxide (NO) originates from the upper airways, and takes action, to varying extents, in regulation, protection and defense, as well as in noxious processes. Nitric oxide retains important functions in a wide range of physiological and pathophysiological processes of the human body, including vaso regulation, antimicrobial activity, neurotransmission and respiration. This review article reports the ongoing investigations regarding the source, biology and relevance of NO within upper respiratory tract. In addition, we discuss the role of NO, originating from nasal and paranasal sinuses, in inflammatory disorders such as allergic rhinitis, sinusitis, primary ciliary dyskinesia, and cystic fibrosis. PMID- 27356535 TI - Human Embryonic and Induced Pluripotent Stem Cell Based Toxicity Testing Models: Future Applications in New Drug Discovery. AB - New drug discovery (NDD) is a fascinating discipline encompassing different facets of medicine, pharmacology, biotechnology and chemistry. NDD is very often restricted by efficacy or safety problems of the new clinical candidate in human patients. Drug regulatory authorities have provided various guidelines for advancement of safe new chemical entities (NCEs) in clinical trials which must be strictly followed. In spite of this, various drugs have failed in clinical trials or withdrawn from market because of human safety issues related to cardiotoxicity, hepatotoxicity, neurotoxicity and teratogenicity. The failure of safety prediction was pointed to species specificity issues, lack of mechanistic toxicity data and inadequate clinical trials. These drugs not only affect human health but also cause loss of resources and time. The species specificity issues are partially addressed by use of primary human cells but their availability is very limited. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) offer sources for generation of an unlimited number of human somatic cells. The emergence of mechanistic models for toxicity testing with transcriptomics, proteomics along with toxicokinetics readouts based on hESCs and hiPSCs is paving the way to design new human relevant testing strategies. Introduction of these models at the timeframe of lead selection and optimization in parallel with in vitro pharmacokinetic studies will significantly reduce compound attrition rate by selection of safer lead molecules. We focused on upcoming hESCs and hiPSCs based toxicity testing models and their future role to address safety gaps of present drug discovery and development. PMID- 27356534 TI - Emerging Roles of Protein S-Nitrosylation in Macrophages and Cancer Cells. AB - Despite long and intensive investigation, the mechanisms by which nitric oxide (NO) regulates immune function and carcinogenesis remain incompletely understood. Protein S-nitrosylation, the covalent attachment of a nitroso group to a cysteine thiol, has emerged as a central mechanism of NO-dependent cellular regulation. In particular, recent research has revealed important roles for S nitrosylation/denitrosylation in modulating the activity of macrophage and tumor cell proteins, implicating Snitrosylation in the regulation of macrophage function as well as in tumor development and response to therapy. This review summarizes recent progress in the identification and characterization of S nitrosylated proteins in macrophages and cancer cells. The review highlights key findings and insights obtained from functional and proteomic studies about the roles of S-nitrosylation in signaling, transcription, apoptosis and other cellular processes relevant to macrophage function and cancer progression. Some of the implications of recent discoveries for the development of novel anticancer approaches are also discussed. PMID- 27356536 TI - The Immunoregulatory Activity of Mesenchymal Stem Cells: 'State of Art' and 'Future Avenues'. AB - Mesenchymal stem cells are spindle-like plastic adherent multipotent cells that can differentiate into multiple specialized cell types including osteoblasts, chondrocytes and adipocytes. They were isolated from many tissues and organs and they contribute to the maintenance and regeneration of several tissues. Besides their ability of self-renewal, they have recently been shown to have a clinical/therapeutic potential particularly for their immunomodulatory properties. Indeed recent studies suggested a potential application of MSCs for the treatment of experimental autoimmune disorders. It was demonstrated that their effects are in part mediated by the release of soluble factors or extracellular vesicles, including exosomes and microvesicles, stimulating or inhibiting target cells. This review will describe the secretome of MSCs, pointing the attention on the components relevant for their immunodulatory activities. PMID- 27356537 TI - Mechanism of Action of Flavonoids in Prevention of Inflammation- Associated Skin Cancer. AB - Skin cancer in humans represents about 30% of all new cancers and is by far the most common malignancy in the Caucasian population. Exposure to radiations especially ultraviolet-B (UV-B) radiation is the major cause for development of skin cancers along with other chemical or biological factors. The growing incidence rates of skin cancer around the world, demand the need for new treatment options. Understanding the etiology and pathogenesis of skin cancer is therefore crucial for developing an effective drug against this prevailing disease. Medicinal plants are rich with numerous secondary metabolites such as flavonoids, which are now known to treat various chronic diseases, including inflammations and cancers. Flavonoids are sub-classified in to flavones, flavonols, iosflavones, flavanones, flavanols and anthocyanidins. They act on different targets including scavenging reactive oxygen species (ROS), regulation of the cell cycle, and initiation of DNA repair mechanisms, apoptotic induction and inhibition of metastasis. Innumerable evidence suggested that an increased consumption of flavonoid-rich fruits and vegetables rendered DNA protection to normal skin exposed to carcinogens such as UV-B radiation. Flavonoids also showed the potential to induce cell death mechanisms in melanoma, the most dreadful form of skin cancer. This comprehensive review presents flavonoids and their mechanism of action in relation to inflammation and skin cancer management. PMID- 27356538 TI - Heat Shock Protein 70s as Potential Molecular Targets for Colon Cancer Therapeutics. AB - BACKGROUND: Targeted drugs modulate selective pathways activated or repressed only in cancer cells, resulting in a higher response to chemotherapy with less severe side effects. The use of a selected member of the heat shock protein 70 family (HSP70) as an effective therapeutic target in the treatment of colorectal cancer (CRC) will be the focus of this review. METHODS: We generated two main questions for this study: 1) What are the current and potential future molecular therapies in CRC? 2) Can selective members of the HSP70 family advance drug design and drug discovery for treatment of CRC patients? We discuss related articles based on their significance and translational contributions to the existing literature. RESULTS: The first part of this review discusses molecularly targeted agents that are currently used successfully in the clinic for the treatment of patients with CRC and highlights several novel targeted agents that are being investigated in ongoing trials. The second part of this review focuses on the unique tumorigenic functions of heat shock proteins, particularly mortalin 2, an essential heat shock protein for mitochondrial biogenesis in normal cells and a dominant oncoprotein in colon cancer cells. Basic and clinical studies have justified mortalin-2 as a potential molecular target, and its inhibition could dramatically improve patients' responses to standard chemotherapies. CONCLUSION: Further understanding of the contributions of HSP70 family members to CRC at the molecular level, combined with translation of new concepts into effective targeted therapies, are anticipated to improve clinical outcomes and increase the therapeutic synergy with combination treatment with cytotoxic agents. PMID- 27356539 TI - Synthesis and Bioactivity of (R)-Ricinoleic Acid Derivatives: A Review. AB - (R)-Ricinoleic acid (RA) [(12R,9Z)-hydroxyoctadecenoic acid], the main compound of castor seed oil, because of its unusual structure readily undergoes multi directional chemical and biochemical transformations to produce derivatives with the retained carbon skeleton or with its degradation. Many of these are of high biological activity, as documented by an in vitro study, and possess therapeutic potential. This review article provides an overview of the recent developments in the area of synthesis of RA based compounds with anticancer and antimicrobial activities. Moreover, the antiinflammatory and analgesic properties of some ricinoleic acid derivatives are also highlighted. PMID- 27356540 TI - Neurotrophins' Modulation by Olive Polyphenols. AB - BACKGROUND: Polyphenols are probably the most known and investigated molecules of nutritional interest as micronutrients present in abundance in our diet. Some of the most important food sources of polyphenols in the Mediterranean diet are olives and olive oil. A growing body of evidence from animal models to clinical studies indicates that polyphenol compounds may have neuroprotective effects in several pathologies of the nervous system through the control of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction. OBJECTIVE: Based on the most recent scientific literature, dietary intake of polyphenols attenuates oxidative stress and reduces risk for related neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, stroke, multiple sclerosis and Huntington's disease. Also at the peripheral level, they act as antioxidant, defending tissues against oxidative damage and scavenging free radicals. RESULTS: Recent findings in animal models and humans show that polyphenols may have a role in regulating neurotrophins levels, in particular nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF), suggesting that polyphenols may also induce their protective effects through the potentiation of neurotrophins action. NGF and BDNF, primarily known as biological mediators stimulating neuron growth, proliferation, survival and differentiation are recently studied also as metabotrophic factors, acting on glucose and energy metabolism, pancreatic beta cells and cardiovascular homeostasis. CONCLUSION: In this context, a better understanding of the effects of polyphenols on neurotrophins and their receptors (TrkA, TrkB, p75NTR) could certainly generate interest for drug discovery and also for the potential dietary prevention of several neurological and cardiometabolic diseases. PMID- 27356541 TI - A Review of Stapled Peptides and Small Molecules to Inhibit Protein-Protein Interactions in Cancer. AB - Disruption of binding of two or more molecules to a protein surface is a common basis of inhibition of many biological activities. Smallmolecule inhibitors, antibodies, proteins, and peptidomimetics have been examined as ways to antagonize receptor activity. The peptide alpha-helix plays a crucial role in the function of many proteins. Hence, much effort has been invested in mimicking alpha-helices at the binding interface of two proteins to competitively inhibit their interactions. Peptide stapling involves choosing two amino acids on the same face of a native peptide sequence for substitution with non-native amino acids whose side chains can be "stapled" together. The focus of this review is to survey the prevalence in literature of stapled peptides and small-molecule antagonists of interactions of selected mammalian cancer targets, such as beta catenin, BH3-only members of the Bcl-2 family of proteins, eIF4E/G, estrogen receptor complexes, EZH2, Mdm2, Notch, p110alpha, and survivin. The increasing interest in protein targets currently considered to be "undruggable" with greater selectivity for existing targets, with the goal of overcoming the omnipresent problem of resistance, could be served well by utilizing information about protein-protein interactions to develop both small-molecule and stapled peptide inhibitors. PMID- 27356542 TI - Promising Diabetes Therapy Based on the Molecular Mechanism for Glucose Toxicity: Usefulness of SGLT2 Inhibitors as well as Incretin-Related Drugs. AB - Pancreatic beta-cell dysfunction and insulin resistance are the main characteristics of type 2 diabetes. Chronic exposure of beta-cells to hyperglycemia leads to the deterioration of beta-cell function. Such phenomena are well known as pancreatic beta-cell glucose toxicity. MafA, a strong transactivator of insulin gene, is particularly important for the maintenance of mature beta-cell function, but its expression level is significantly reduced under diabetic conditions which is likely associated with beta-cell failure. Reduction of incretin receptor expression level in beta-cells in diabetes is also likely associated with beta-cell failure. On the other hand, incretin-related drugs and sodium-glucose co-transporter 2 (SGLT2) inhibitors are promising diabetes therapy based on the mechanism for pancreatic beta-cell glucose toxicity. Indeed, it was shown that incretin-related drugs exerted protective effects on beta-cells through the augmentation of IRS-2 expression especially in the presence of pioglitazone. It was also shown that incretin-related drug and/or pioglitazone exerted more protective effects on beta-cells at the early stage of diabetes compared to the advanced stage. SGLT2 inhibitors, new hypoglycemic agents, also exert beneficial effects for the protection of pancreatic beta-cells as well as for the reduction of insulin resistance in various insulin target tissues. Taken together, it is important to select appropriate therapy based on the molecular mechanism for glucose toxicity. PMID- 27356543 TI - Development of C-Methyl Branched Purine Ribonucleoside Analogs: Chemistry, Biological Activity and Therapeutic Potential. AB - In this review, we first highlighted on C-methyl-branched nucleosides and nucleotides approved as anti-hepatitis C infection (HCV) drugs, their mechanism of action and recent progress in the development of new clinical candidates. Then, we report on our attempt to develop several C-methyl nucleosides/tides potentially useful for treatment of various diseases such cancer, pain, epilepsy and glaucoma. Design, synthesis and pharmacological screening of 1'-C-, 2'-C-, 3' C-methyladenosine or other purine/pyrimidine nucleosides allowed us to discover some promising new molecules. 3'-C-Methyladenosine showed antitumor activity against several human tumor cell lines. We have investigated the mechanism of action of 3;-C-methyladenosine that proved to be an effective inhibitor of ribonucleotide reductase. Moreover, we will also summarize the chemical and biological properties of some of the recent N6-substituted and 5', N6 disubstituted 2'-C-methyladenosine derivatives that were synthetized in our laboratory and evaluated as A1 adenosine receptor agonists. 2-Chloro-2'- C-methyl N6-cyclopentyladenosine (2'-Me-CCPA), 5'-chloro-5'-deoxy-N6-(+/-)-(endo-norborn- 2-yl)adenosine (5'Cl5'd-(+/-)-ENBA) and 2'-C-methyl-5'-chloro-5'-deoxy-N6-(+/-) (endonorborn- 2-yl)adenosine (2'-Me-5'Cl5'd-(+/-)-ENBA) displayed high hA1AR affinity and selectivity. 2'-Me-CCPA and 5'Cl5'd-(+/-)-ENBA showed significant analgesic properties. PMID- 27356544 TI - Challenges in Chagas Disease Drug Discovery: A Review. AB - Chagas disease or American trypanosomiasis is a neglected tropical disease caused by the parasite Trypanosoma cruzi. Although the number of infected individuals has decreased, about 6-7 million people are infected worldwide. The chemotherapy drugs currently used are limited to benznidazole and nifurtimox. They are effective in acute phase, congenital transmission and children with chronic infection; however, recent clinical trials have shown limitations in adults with chronic infection, presenting drawbacks during the treatment. Thus, there is an urgent need for new effective, safe and affordable drugs to fight against this complex disease. There were high expectations for azole derivatives as they appeared to be the most promising drugs for the treatment of Chagas disease during the last decade; however, the disappointing results obtained so far in clinical trials evidenced the lack of correlation between preclinical and clinical development. Therefore, the feedback obtained from these studies should define the starting point for addressing a roadmap for the drug discovery process in the fight against this disease. To tackle this challenge, it is important to keep in mind the drug target profile, already defined by panels of experts, and the coordinated work involving multi-disciplinary networks focusing not only on the discovery of new drugs but also on the standardization of the protocols that would allow acceleration in the Chagas disease drug discovery process. PMID- 27356545 TI - Melanogenesis Inhibitors: Strategies for Searching for and Evaluation of Active Compounds. AB - Hyperpigmentation disorders constitute important medical and aesthetical conditions. Dark areas or dark spots on the skin result from inappropriate amount and/or deposition of skin pigments - melanins. Several depigmenting agents, such as kojic acid, arbutin, aloesin, ellagic acid, resveratrol, azelaic acid, niacinamide, tretinoin, glycolic acid, lactic acid, and citric acid, have already been identified and are used in topical drugs or cosmetic formulations for the treatment of hyperpigmentations. However, these compounds are characterized by insufficient effectiveness and multiple adverse effects. As a result, there is still a need for searching for new active substances. The current paper summarizes strategies for searching for novel melanogenesis inhibitors. In the review, they are divided according to approach, into in silico, in vitro and in vivo experiments. In silico research includes computational studies with models of tyrosinase and di-copper complexes. The in vitro approach is based on tests using tyrosinase (a key enzyme in melanin biosynthesis), cell cultures, cell co cultures, pigmented human skin equivalents or Streptomyces bikiniensis model. In vivo studies involve zebrafish, rodents or humans. Examples of protocols and laboratory procedures are presented, with a focus on utilization of various models for evaluation of mechanisms of action of tested compounds. The potential limitations of the methods are also discussed, together with future perspectives in the field of searching for melanogenesis inhibitors. PMID- 27356546 TI - Tea flavonoids for bone health: from animals to humans. AB - Osteoporosis is a skeletal disease characterized by a deterioration of bone mass and bone quality that predisposes an individual to a higher risk of fragility fractures. Emerging evidence has shown that the risk for low bone mass and osteoporosis-related fractures can be reduced by nutritional approaches aiming to improve bone microstructure, bone mineral density, and strength. Tea and its flavonoids, especially those of black tea and green tea, have been suggested to protect against bone loss and to reduce risk of fracture, due to tea's antioxidant and anti-inflammatory properties. Based on the results of animal studies, moderate intake of tea has shown to benefit bone health as shown by mitigation of bone loss and microstructural deterioration as well as improvement of bone strength and quality. Epidemiological studies have reported positive, insignificant, and negative impacts on bone mineral density at multiple skeletal sites and risk of fracture in humans with habitual tea consumption. There are limited human clinical trials that objectively and quantitatively assessed tea consumption and bone efficacy using validated outcome measures in a population at high risk for osteoporosis, along with safety monitoring approach. This review summarizes the current state of knowledge of laboratory animal research, epidemiological observational studies, and clinical trials assessing the skeletal effects of tea and its active flavonoids, along with discussion of relevant future directions in translational research. PMID- 27356548 TI - Social and Emotional Competencies Evaluation Questionnaire-Teacher's Version: Validation of a Short Form. AB - The Social and Emotional Competencies Evaluation Questionnaire-Teacher's version, Short Form (QACSE-P-SF) allows teachers to assess their students' social and emotional competencies, having been designed for program evaluation. Thirty-nine teachers completed the QACSE-P-SF, regarding 657 students (fourth to ninth grades). Factor analyses supported a six-factor structure with acceptable internal consistency. Sex differences were found with teachers reporting girls as having higher scores on Self-Control, Social Awareness, Relationship Skills, and Responsible Decision Making. Developmental differences were also found with fourth-grade students presenting higher levels of Social Awareness and Relationship Skills than older students. The final version of the QACSE-P-SF is composed by 30 items, organized into six scales and less time consuming than the previous version for teachers who need to assess full classes. PMID- 27356547 TI - Effects of maternal vitamin B12 supplementation on early infant neurocognitive outcomes: a randomized controlled clinical trial. AB - Maternal nutritional status during pregnancy impacts fetal brain development. Vitamin B12 plays a vital role in neuronal development. However, findings from studies on the association between maternal B12 status and child cognitive functions have been inconsistent. We performed a randomized, placebo-controlled clinical trial of oral B12 supplementation (50 ug) beginning at <14 weeks of gestation through a 6-week post-partum. In the present study, we report the effects of maternal B12 supplementation on cognitive development in infants at 9 months of age on Bayley Scales of Infant Development-III (BSID-III). One hundred eighty-three pregnant women received vitamin B12, and 183 received placebo. Nine month BSID-III development score was available in 178 infants. There were no significant differences in maternal sociodemographic characteristics and baseline biochemical measures between infants who underwent BSID-III evaluation and infants who were not evaluated. There were no significant differences in any of the subscales of BSID-III between infants born to mothers who received B12 supplementation (n = 78) vs. placebo (n = 100). On multiple regression analysis, elevated maternal total homocysteine (tHcy) levels adjusted for treatment group, birthweight, parity, income and home environment at second trimester of pregnancy were significantly negatively associated with expressive language (beta = 3.13 points, P < 0.001), and in third trimester of pregnancy with expressive language (beta = -2.29 points, P < 0.001) and fine motor (beta = -1.41 points, P = 0.005) domains of BSID-III. While no significant effects of maternal B12 supplementation were seen on cognitive development in infants at 9 months of age, elevated maternal tHcy levels were associated with poorer cognitive performance in some of the subdomains of BSID-III. In pregnant women with elevated tHcy levels and or B12 deficiencies, it may be worthwhile to study the impact of longer term maternal supplementation on infant cognitive outcomes. PMID- 27356549 TI - Robust pro-inflammatory immune response is associated with serological cure in patients with syphilis: an observational study. AB - OBJECTIVES: Approximately 15% of adequately treated patients with early syphilis remain serofast. Pathogenesis and clinical significance of this phenomenon is unclear. The objective of this study was to determine whether there is any association between host immune response and treatment outcome (serofast state or proper serological response). METHODS: Forty-four patients with secondary syphilis were enrolled to this study. Levels of pro-inflammatory cytokines such as interferon-gamma, tumour necrosis factor-alpha and interleukin-6 were measured before treatment and 8 hours after injection of antibiotic. RESULTS: After 1 year, based on the serological response patients were stratified into two groups: (1) proper serological response (n=31) and (2) serofast state (n=9). The serological cure rate was 77.5% at 12 months after treatment. Patients with proper serological response had significantly higher levels of analysed cytokines (at baseline and 8 hours after treatment) compared with the serofast state group (p<0.05). CONCLUSIONS: We showed that robust host pro-inflammatory immune response to infection may be the predictive factor of serological cure. The treatment outcome may be also associated with the magnitude of immune reaction occurring during the treatment. PMID- 27356550 TI - [A time of change for men's health: a process of increasing medicalisation?]. AB - These days, men suffer from a bad reputation when the media talk about health matters. Nonetheless, talking about men's health is problematic, as it considers the health behaviour of the male gender in an essentialistic manner. Such discourse is socially under-differentiated, frequently dramatises the gender difference rather than explaining it, makes inappropriate individualisations, draws on questionable benchmarks, makes women the positive model without first reflecting, and is ahistorical. Gender patterns have a major significance for health behaviour and have indeed considerably changed the health behaviour of men and women over the last 250 years. Women have been more seriously medicalised and have, on account of their life expectancy, profited more from modernisation, developments in hygiene, the expansion of medical services and state healthcare policies. However, over the last 30 years, besides a continuing parallel medicalisation of men, signs of it increasing can also be seen. Their behaviour has become more compatible with health. A more adequate description of the situation could be achieved through a more concentrated observation of health lifestyles. PMID- 27356552 TI - Ipr1 modified BCG as a novel vaccine induces stronger immunity than BCG against tuberculosis infection in mice. AB - Tuberculosis is a major challenge to global public health. However, the Bacille Calmette-Guerin (BCG), the only vaccine available against tuberculosis, has been questioned for the low protective effect. The present study used the mouse gene intracellular pathogen resistance I (Ipr1) gene to alter the current BCG vaccine and evaluated its immunity effect against tuberculosis. This study also investigated the intrinsic relationships of Ipr1 and innate immunity. The reformed BCG (BCGi) carrying the Ipr1 gene was constructed. The mice were intranasally challenged with the M. tuberculosis H37Rv strain after vaccination with BCGi. Protection efficacy of the vaccine was assessed by the organ coefficient, bacterial load and pathological changes in the lung. The differential expression of 113 immune-related genes between BCGi and BCG groups were detected by an oligo microarray. According to the results of organ coefficient, bacterial load and pathological changes in the organization, BCGi had been shown to have stronger protective effects against M. tuberculosis than BCG. The oligo microarray and reverse transcription-quantitative polymerase chain reaction further revealed that the Ipr1 gene could upregulate the expression of 13 genes, including a >3-fold increase in Toll-like receptor (TLR)4 and 10-fold increase in surfactant protein D (sftpd). The two genes not only participate in innate immunity against pathogens, but also are closely interrelated. Ipr1 could activate the TLR4 and sftpd signaling pathway and improve the innate immunity against tuberculosis, therefore Ipr1 modified BCG may be a candidate vaccine against M. tuberculosis. PMID- 27356553 TI - Effect of hyaluronic acid with or without scaffold material on the regeneration of tympanic membrane perforations. PMID- 27356551 TI - Altered hypermetabolic response to cortical spreading depolarizations after traumatic brain injury in rats. AB - Spreading depolarizations are waves of near-complete breakdown of neuronal transmembrane ion gradients, free energy starving, and mass depolarization. Spreading depolarizations in electrically inactive tissue are associated with poor outcome in patients with traumatic brain injury. Here, we studied changes in regional cerebral blood flow and brain oxygen (PbtO2), glucose ([Glc]b), and lactate ([Lac]b) concentrations in rats, using minimally invasive real-time sensors. Rats underwent either spreading depolarizations chemically triggered by KCl in naive cortex in absence of traumatic brain injury or spontaneous spreading depolarizations in the traumatic penumbra after traumatic brain injury, or a cluster of spreading depolarizations triggered chemically by KCl in a remote window from which spreading depolarizations invaded penumbral tissue. Spreading depolarizations in noninjured cortex induced a hypermetabolic response characterized by a decline in [Glc]b and monophasic increases in regional cerebral blood flow, PbtO2, and [Lac]b, indicating transient hyperglycolysis. Following traumatic brain injury, spontaneous spreading depolarizations occurred, causing further decline in [Glc]b and reducing the increase in regional cerebral blood flow and biphasic responses of PbtO2 and [Lac]b, followed by prolonged decline. Recovery of PbtO2 and [Lac]b was significantly delayed in traumatized animals. Prespreading depolarization [Glc]b levels determined the metabolic response to clusters. The results suggest a compromised hypermetabolic response to spreading depolarizations and slower return to physiological conditions following traumatic brain injury-induced spreading depolarizations. PMID- 27356554 TI - Management of laryngoceles by transoral robotic surgery. AB - We herein report our experience with the management of laryngoceles using transoral robotic surgery (TORS). A bicentric retrospective study was conducted from November 2009 to September 2015. The inclusion criteria were treatment of a laryngocele by TORS and no malignancy on definitive histopathology. Surgery was performed using the Da Vinci (Intuitive(r)) surgical robot. Surgical methods and post-operative outcomes were evaluated. Eight patients (four men and four women) presenting with a laryngocele (one bilateral case) were included (mean age 61.8 years). There was one covering tracheotomy. The average post-operative stay was 3.75 days. Three patients treated for a combined laryngocele had a nasogastric feeding tube inserted for 5 days. One patient experienced late laryngeal bleeding that required surgical treatment. TORS may offer an efficient treatment option for laryngoceles. The use of precise and flexible instruments and a three dimensional camera allow fine dissection of these tumours, preserving the glottic space and vocal function, even for combined laryngoceles extending deep within the neck.Evidence level: 4. PMID- 27356555 TI - Long term results of the titanium clip prosthesis. AB - The objective of the study is to evaluate the long term results of ossiculoplasty using the clip titanium partial ossicular replacement prosthesis. This study retrospectively reviews the partial ossiculoplasty conducted using clip titanium partial ossicular replacement prosthesis at a tertiary referral center. Audiometric outcomes and intraoperative findings were postoperatively measured from revision surgery of 47 ears (20 women, 27 men, mean age 43 years) averaging 6.5 years. The overall air-bone gap decreased from 25.7 dB preoperatively to 16.8 dB 6.5 years postoperatively (p <= 0.001, eta p2 = 0.210). An air-bone gap of <20 dB was present in 28 % of ears preoperatively and increased to 72 % postoperatively. In revision (n = 30) and primary tympanoplasties (n = 17), the preoperative air-bone gaps were reduced from 28.9 and 20.1 to 18.7 dB (p <= 0.001, eta p2 = 0.240) and 13.2 dB (p = 0.033, eta p2 = 0.192), respectively. In canal wall down (n = 15) procedures and tympanoplasties with intact canal wall (n = 32), the mean air-bone gaps diminished from 28.9 to 18.1 dB (p = 0.02, eta p2 = 0.245) and 24.2 to 16.1 dB (p <= 0.001, eta p2 = 0.221), respectively. In our own revision tympanoplasties (n = 8) and second look operations (n = 6), we found that the prostheses were safe to remove without any deleterious effects. Two prostheses were dislocated from the stapes' head due to recurrent cholesteatoma. Therefore, it can be concluded that ossiculoplasty using the clip partial ossicular replacement prosthesis allows for good and reliable long term hearing results. Also, the flexible strips reveal no adverse effects on the encompassed stapes' head and do not complicate revision surgery. PMID- 27356556 TI - The admission patterns of octogenerians nonagenerians and centenarians to the Department of Otoloaryngology. AB - Life expectancy in Israel has risen by almost 6 years during the last 25 years, and the proportion of people 65 years of age or older is expected to reach 12 % of the total population by 2020. A substantial increase in the workload for Otolaryngologists and Head and Neck surgeons is anticipated. Our goal was to characterize the admissions of patients 80 years of age and older to the Department of Otolaryngology, Head and Neck Surgery in a tertiary medical center. The study group included all patients 80 years of age and older who were admitted to the Department of OTOHNS in our institute between 2009 and 2013. There were two control groups for comparison divided by age; one group 40-59 years old and the other group 60-79 years old. There were 385 admissions of 317 patients aged 80-103 years (4.2 % of overall admissions). Over the study period, admissions of patients over 80 years increased on average by 3 % per annum (p = 0.4), and those patients over 90 years old by 52 % per annum (p < 0.001). The most common indication was HN malignancy (28.8 %) followed by otologic disorders (22.0 %). Of the overall 158 operations conducted, 131 patients (82.9 %) underwent elective procedures (mainly oncology) and 27 patients (17.1 %) underwent emergent procedures. The distribution of the reasons for admission of the patients older than 80 years is surprisingly different from that of the "younger" patients. With life expectancy rising, our study predicts a workload increase mainly in the HN oncologic and otologic services. PMID- 27356558 TI - Thin Film Silicon Nanowire/PEDOT:PSS Hybrid Solar Cells with Surface Treatment. AB - SiNW/PEDOT:PSS hybrid solar cells are fabricated on 10.6-MUm-thick crystalline Si thin films. Cells with Si nanowires (SiNWs) of different lengths fabricated using the metal-catalyzed electroless etching (MCEE) technique have been investigated. A surface treatment process using oxygen plasma has been applied to improve the surface quality of the SiNWs, and the optimized cell with 0.7-MUm-long SiNWs achieved a power conversion efficiency (PCE) of 7.83 %. The surface treatment process is found to remove surface defects and passivate the SiNWs and substantially improve the average open circuit voltage from 0.461 to 0.562 V for the optimized cell. The light harvesting capability of the SiNWs has also been investigated theoretically using optical simulation. It is found that the inherent randomness of the MCEE SiNWs, in terms of their diameter and spacing, accounts for the excellent light harvesting capability. In comparison, periodic SiNWs of comparable dimensions have been shown to exhibit much poorer trapping and absorption of light. PMID- 27356557 TI - Lifetime Risk for Sudden Cardiac Death in the Community. AB - BACKGROUND: Sudden cardiac death (SCD) is a leading cause of death in the United States and often occurs without previous cardiac symptoms. Lifetime risk for SCD and the influence of established risk factors on lifetime risks for SCD have not been estimated previously. METHODS AND RESULTS: We followed Framingham Heart Study participants who were free of cardiovascular disease before their earliest examination. SCD was defined as death attributed to coronary heart disease within 1 hour of symptom onset without another probable cause of death, as adjudicated by a panel of 3 physicians. Lifetime risk for SCD was estimated to 85 years of age for men and women, with death attributed to other causes as the competing risk, and stratified by risk factor levels. We followed 2294 men and 2785 women for 160 396 person-years; 375 experienced SCD. At 45 years of age, lifetime risks were 10.9% (95% CI, 9.4-12.5) for men and 2.8% (95% CI, 2.1-3.5) for women. Greater aggregate burden of established risk factors was associated with a higher lifetime risk for SCD. Categorizing men and women solely by blood pressure levels resulted in a clear stratification of lifetime risk curves. CONCLUSIONS: We present the first lifetime risk estimates for SCD. Greater aggregate risk factor burden, or blood pressure level alone, is associated with higher lifetime risks for SCD. This high risk of premature death attributed to SCD (approximately 1 in 9 men and 1 in 30 women) should serve as a motivator of public health efforts in preventing and responding to SCD. PMID- 27356559 TI - Inexpensive transparent nanoelectrode for crystalline silicon solar cells. AB - We report an easily manufacturable and inexpensive transparent conductive electrode for crystalline silicon (c-Si) solar cells. It is based on a silver nanoparticle network self-forming in the valleys between the pyramids of a textured solar cell surface, transformed into a nanowire network by sintering, and subsequently "buried" under the silicon surface by a metal-assisted chemical etching. We have successfully incorporated these steps into the conventional c-Si solar cell manufacturing process, from which we have eliminated the expensive screen printing and firing steps, typically used to make the macro-electrode of conducting silver fingers. The resulting, preliminary solar cell achieved power conversion efficiency only 14 % less than the conventionally processed c-Si control cell. We expect that a cell with an optimized processing will achieve at least efficiency of the conventional commercial cell, but at significantly reduced manufacturing cost. PMID- 27356560 TI - Elucidating Protein Involvement in the Stabilization of the Biogenic Silver Nanoparticles. AB - Silver nanoparticles (AgNPs) have been broadly used as antibacterial and antiviral agents. Further, interests for green AgNP synthesis have increased in recent years and several results for AgNP biological synthesis have been reported using bacteria, fungi and plant extracts. The understanding of the role and nature of fungal proteins, their interaction with AgNPs and the subsequent stabilization of nanosilver is yet to be deeply investigated. Therefore, in an attempt to better understand biogenic AgNP stabilization with the extracellular fungal proteins and to describe these supramolecular interactions between proteins and silver nanoparticles, AgNPs, produced extracellularly by Aspergillus tubingensis-isolated as an endophytic fungus from Rizophora mangle-were characterized in order to study their physical characteristics, identify the involved proteins, and shed light into the interactions among protein-NPs by several techniques. AgNPs of around 35 nm in diameter as measured by TEM and a positive zeta potential of +8.48 mV were obtained. These AgNPs exhibited a surface plasmon resonance (SPR) band at 440 nm, indicating the nanoparticles formation, and another band at 280 nm, attributed to the electronic excitations in tryptophan, tyrosine, and/or phenylalanine residues in fungal proteins. Fungal proteins were covalently bounded to the AgNPs, mainly through S-Ag bonds due to cysteine residues (HS-) and with few N-Ag bonds from H2N- groups, as verified by Raman spectroscopy. Observed supramolecular interactions also occur by electrostatic and other protein-protein interactions. Furthermore, proteins that remain free on AgNP surface may perform hydrogen bonds with other proteins or water increasing thus the capping layer around the AgNPs and consequently expanding the hydrodynamic diameter of the particles (~264 nm, measured by DLS). FTIR results enabled us to state that proteins adsorbed to the AgNPs did not suffer relevant secondary structure alteration upon their physical interaction with the AgNPs or when covalently bonded to them. Eight proteins in the AgNP dispersion were identified by mass spectrometry analyses. All these proteins are involved in metabolic pathways of the fungus and are important for carbon, phosphorous and nitrogen uptake, and for the fungal growth. Thereby, important proteins for fungi are also involved in the formation and stabilization of the biogenic AgNPs. PMID- 27356561 TI - Functionalization of Carbon Nanomaterial Surface by Doxorubicin and Antibodies to Tumor Markers. AB - The actual task of oncology is effective treatment of cancer while causing a minimum harm to the patient. The appearance of polymer nanomaterials and technologies launched new applications and approaches of delivery and release of anticancer drugs. The goal of work was to test ultra dispersed diamonds (UDDs) and onion-like carbon (OLCs) as new vehicles for delivery of antitumor drug (doxorubicin (DOX)) and specific antibodies to tumor receptors. Stable compounds of UDDs and OLCs with DOX were obtained. As results of work, an effectiveness of functionalization was 2.94 % w/w for OLC-DOX and 2.98 % w/w for UDD-DOX. Also, there was demonstrated that UDD-DOX and OLC-DOX constructs had dose-dependent cytotoxic effect on tumor cells in the presence of trypsin. The survival of adenocarcinoma cells reduced from 52 to 28 % in case of incubation with the UDD DOX in concentrations from 8.4-2.5 to 670-20 MUg/ml and from 72 to 30 % after incubation with OLC-DOX. Simultaneously, antibodies to epidermal growth factor maintained 75 % of the functional activity and specificity after matrix-assisted pulsed laser evaporation deposition. Thus, the conclusion has been made about the prospects of selected new methods and approaches for creating an antitumor agent with capabilities targeted delivery of drugs. PMID- 27356562 TI - Electroless Gold-Modified Diatoms as Surface-Enhanced Raman Scattering Supports. AB - Porous biosilica from diatom frustules is well known for its peculiar optical and mechanical properties. In this work, gold-coated diatom frustules are used as low cost, ready available, functional support for surface-enhanced Raman scattering. Due to the morphology of the nanostructured surface and the smoothness of gold deposition via an electroless process, an enhancement factor for the p mercaptoaniline Raman signal of the order of 10(5) is obtained. PMID- 27356563 TI - Enhanced performance of CH3NH3PbI3-x Cl x perovskite solar cells by CH3NH3I modification of TiO2-perovskite layer interface. AB - In this work, perovskite solar cells (PSCs) with CH3NH3PbI3-x Cl x as active layer and spiro-OMeTAD as hole-transport media have been fabricated by one-step method. The methylammonium iodide (CH3NH3I) solution with different concentrations is used to modify the interface between mesoporous TiO2 (meso TiO2) film and CH3NH3PbI3-x Cl x perovskite layer. Several techniques including X ray diffraction, scanning electron microscopy, optical absorption, electrochemical impedance spectroscopy (EIS) and photoluminescence are used to investigate the effect of the interfacial modification. It is found that the interfacial modification by CH3NH3I enhance the crystallinity and increase the grain size of CH3NH3PbI3-x Cl x layer, and improve the surface wetting properties of perovskite precursor on meso-TiO2 film. The sunlight absorption and external quantum efficiency of PSCs in the visible region with wavelength less than 600 nm have been improved. The Nyquist plots obtained from the EIS suggest that the CH3NH3I modification can reduce the charge recombination rates. The photoluminescence measurement shows that the exciton dissociation in the modified devices is more effective than that in the control samples. The photovoltaic performance of the modified devices can be significantly improved with respect to the reference (control) devices. The CH3NH3I modified devices at the optimized concentration demonstrate the average power conversion efficiency of 12.27 % in comparison with the average efficiency of 9.68 % for the reference devices. PMID- 27356564 TI - Simulation and Experimental Study on Anti-reflection Characteristics of Nano patterned Si Structures for Si Quantum Dot-Based Light-Emitting Devices. AB - Surface-textured structure is currently an interesting topic since it can efficiently reduce the optical losses in advanced optoelectronic devices via light management. In this work, we built a model in finite-difference time-domain (FDTD) solutions by setting the simulation parameters based on the morphology of the Si nanostructures and compared with the experimental results in order to study the anti-reflection behaviors of the present nano-patterned structures. It is found that the reflectance is gradually reduced by increasing the depth of Si nanostructures which is in well agreement with the experimental observations. The reflectance can be lower than 10 % in the light range from 400 to 850 nm for Si nano-patterned structures with a depth of 150 nm despite the quite low aspect ratio, which can be understood as the formation of gradually changed index layer and the scattering effect of Si nano-patterned structures. By depositing the Si quantum dots/SiO2 multilayers on nano-patterned Si substrate, the reflectance can be further suppressed and the luminescence intensity centered at 820 nm from Si quantum dots is enhanced by 6.6-fold compared with that of flat one, which can be attributed to the improved light extraction efficiency. However, the further etch time causes the reduction of luminescence intensity from Si quantum dots which may ascribe to the serious surface recombination of carriers. PMID- 27356565 TI - Local Magnetoelectric Effect in La-Doped BiFeO3 Multiferroic Thin Films Revealed by Magnetic-Field-Assisted Scanning Probe Microscopy. AB - Multiferroic La-doped BiFeO3 thin films have been prepared by a sol-gel plus spin coating process, and the local magnetoelectric coupling effect has been investigated by the magnetic-field-assisted scanning probe microscopy connected with a ferroelectric analyzer. The local ferroelectric polarization response to external magnetic fields is observed and a so-called optimized magnetic field of ~40 Oe is obtained, at which the ferroelectric polarization reaches the maximum. Moreover, we carry out the magnetic-field-dependent surface conductivity measurements and illustrate the origin of local magnetoresistance in the La-doped BiFeO3 thin films, which is closely related to the local ferroelectric polarization response to external magnetic fields. This work not only provides a useful technique to characterize the local magnetoelectric coupling for a wide range of multiferroic materials but also is significant for deeply understanding the local multiferroic behaviors in the BiFeO3-based systems. PMID- 27356566 TI - [Risk assessment on cervical cancer in women with cytology atypical squamous cells of undetermined significance but negative human papillomavirus]. AB - OBJECTIVE: To assess the risk of cervical cancer and high grade cervical intraepithelial in women with negative human papillomavirus (HPV) and cytology atypical squamous cells of undetermined significance (ASC-US) and to provide evidence for clinical management. METHODS: We pooled 17 population-based cross sectional studies which were conducted across China from 1999 to 2008. Totally, 30 371 women aged 17-59 were included in these studies. All women received liquid based cytology test (LBC), HPV testing (hybrid capture 2 test, HC2) and visual inspection with acetic acid test (VIA). Women with any positive result from above tests were referred to colposcopic examination. Totally, 28 810 women with complete results from HPV, cytology and pathology were included in the final analysis. Women with negative HPV (LBC-/HPV-) or negative cytology (LBC-) results served as the control, respectively. Risk on high grade cervical intraepithelial neoplasia (CIN2+) was calculated for women with HPV negative and ASC-US results (ASC-US/HPV-). RESULTS: There were 22 003 women with LBC-/HPV-, 24 139 women with LBC-, and 1 834 with ASC-US/HPV- indentified in our study. CIN2+prevalence rates to the above women appeared as 0.05%, 0.36% and 0.16%, respectively. Compared with women with LBC-/HPV- and women with LBC-, the odds ratios (ORs) for CIN2+in women with ASC-US/HPV-were 3.00 (95%CI: 0.85-10.65) and 0.46 (95%CI:0.15-1.45), with adjusted ORs as 4.00 (95%CI: 1.08-14.87) and 0.47(95%CI: 0.15-1.49), respectively. CONCLUSIONS: The risk of CIN2+ in women with ASC-US/HPV- was in between the risks of women with LBC-/HPV- or with LBC-. Based on the "equal risk, equal management" principle, women with ASC-US/HPV- were suggested to be followed under the '3-year interval' program, which was the same as for those cytology negative women. However, in areas with limited health resources, the follow-up interval can be extended to 5 years, similar to the management on women with LBC /HPV-. PMID- 27356567 TI - Anti-apolipoprotein A-1 auto-antibodies as active modulators of atherothrombosis. AB - Humoral autoimmune-mediated inflammation plays a role in atherogenesis, and potentially in arterial thrombosis. Anti-apolipoprotein A-1 (apoA-1) IgG have been reported to represent emergent mediators of atherogenesis through Toll-like receptors (TLR) 2, 4 and CD14 signalling. We investigated the role of anti-apoA-1 IgG on tissue factor (TF) expression and activation, a key coagulation regulator underlying atherothrombosis. Atherothrombosis features were determined by immunohistochemical TF staining of human carotid biopsies derived from patients with severe carotid stenosis undergoing elective surgery (n=176), and on aortic roots of different genetic backgrounds mice (ApoE-/-; TLR2-/-ApoE-/- and TLR4-/ ApoE-/-) exposed to passive immunisation with anti-apoA-1 IgG. Human serum levels of anti-apoA-1 IgG were measured by ELISA. In vitro, on human-monocyte-derived macrophages (HMDM) the anti-apoA-1 IgG increased TF expression and activity were analysed by FACS and chromogenic assays in presence of different pharmacological inhibitors. Human serum anti-apoA-1 IgG levels significantly correlated to intraplaque TF expression in carotid biopsies (r=0.31, p<0.001), which was predictive of clinically symptomatic lesions. On HMDM, anti-apoA-1 IgG induced a TLR2, 4 and CD14-dependent increase in TF expression and activity, involving NF kappaB and a c-Jun N-terminal kinase-dependent AP-1 transcription factors. In ApoE-/- mice, anti-apoA-1 IgG passive immunisation significantly enhanced intraplaque TF expression when compared to control IgG. This effect was lost in both TLR2-/-ApoE-/- and TLR4-/-ApoE-/- mice. These results demonstrate that anti apoA-1 IgG are associated with TF expression in human atherosclerotic plaques, induce TF expression in vitro and in vivo through TLR2 and 4 signalling, supporting a possible causal relationship between anti-apoA-1 IgG and atherothrombosis. PMID- 27356568 TI - Load management in elite German distance runners during 3-weeks of high-altitude training. AB - There is a debate on the optimal way of monitoring training loads in elite endurance athletes especially during altitude training camps. In this case report, including nine members of the German national middle distance running team, we describe a practical approach to monitor the psychobiological stress markers during 21 days of altitude training (~2100 m above sea-level) to estimate the training load and to control muscle damage, fatigue, and/or chronic overreaching. Daily examination included: oxygen saturation of hemoglobin, resting heart rate, body mass, body and sleep perception, capillary blood concentration of creatine kinase. Every other day, venous serum concentration of blood urea nitrogen, venous blood concentration of hemoglobin, hematocrit, red and white blood cell were measured. If two or more of the above-mentioned stress markers were beyond or beneath the athlete's normal individual range, the training load of the subsequent training session was reduced. Running speed at 3 mmol L(-1) blood lactate (V3) improved and no athlete showed any signs of underperformance, chronic muscle damage, decrease body and sleep perception as well as activated inflammatory process during the 21 days. The dense screening of biomarkers in the present case study may stimulate further research to identify candidate markers for load monitoring in elite middle- and long-distance runners during a training camp at altitude. PMID- 27356571 TI - "Experimental Oncology" is the Best Scientific Journal in Ukraine according to SCOPUS! AB - International scientific journal "Experimental Oncology" (Publishing House "MORION LLC", Kyiv, Ukraine - R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the NAS of Ukraine, Kyiv, Ukraine) earned high global recognition, receiving the prestigious international award "SCOPUS Awards Ukraine" as a winner in the category "The Best Journal". PMID- 27356570 TI - Identification of differentially expressed genes between lung adenocarcinoma and lung squamous cell carcinoma by gene expression profiling. AB - The present study aimed to identify the differentially expressed genes (DEGs) between lung adenocarcinoma and normal lung tissues, and between lung squamous cell carcinoma and normal lung tissues, with the purpose of identifying potential biomarkers for the treatment of lung cancer. The gene expression profile (GSE6044) was downloaded from the Gene Expression Omnibus database, which included data from 10 lung adenocarcinoma samples, 10 lung squamous cell carcinoma samples, and five matched normal lung tissue samples. After data processing, DEGs were identified using the Student's t-test adjusted via the Benjamini-Hochberg method. Subsequently, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the DEGs was performed using the Database for Annotation, Visualization and Integrated Discovery, and a global network was constructed. A total of 95 upregulated and 241 downregulated DEGs were detected in lung adenocarcinoma samples, and 204 upregulated and 285 downregulated DEGs were detected in lung squamous cell carcinoma samples, as compared with the normal lung tissue samples. The DEGs in the lung squamous cell carcinoma group were enriched in the following three pathways: Hsa04110, Cell cycle; hsa03030, DNA replication; and hsa03430, mismatch repair. However, the DEGs in the lung adenocarcinoma group were not significantly enriched in any specific pathway. Subsequently, a global network of lung cancer was constructed, which consisted of 341 genes and 1,569 edges, of which the top five genes were HSP90AA1, BCL2, CDK2, KIT and HDAC2. The expression trends of the above genes were different in lung adenocarcinoma and lung squamous cell carcinoma when compared with normal tissues. Therefore, these genes were suggested to be crucial genes for differentiating lung adenocarcinoma and lung squamous cell carcinoma. PMID- 27356569 TI - Differences in the timing and magnitude of Pkd1 gene deletion determine the severity of polycystic kidney disease in an orthologous mouse model of ADPKD. AB - Development of a disease-modifying therapy to treat autosomal dominant polycystic kidney disease (ADPKD) requires well-characterized preclinical models that accurately reflect the pathology and biochemical changes associated with the disease. Using a Pkd1 conditional knockout mouse, we demonstrate that subtly altering the timing and extent of Pkd1 deletion can have a significant impact on the origin and severity of kidney cyst formation. Pkd1 deletion on postnatal day 1 or 2 results in cysts arising from both the cortical and medullary regions, whereas deletion on postnatal days 3-8 results in primarily medullary cyst formation. Altering the extent of Pkd1 deletion by modulating the tamoxifen dose produces dose-dependent changes in the severity, but not origin, of cystogenesis. Limited Pkd1 deletion produces progressive kidney cystogenesis, accompanied by interstitial fibrosis and loss of kidney function. Cyst growth occurs in two phases: an early, rapid growth phase, followed by a later, slow growth period. Analysis of biochemical pathway changes in cystic kidneys reveals dysregulation of the cell cycle, increased proliferation and apoptosis, activation of Mek-Erk, Akt-mTOR, and Wnt-beta-catenin signaling pathways, and altered glycosphingolipid metabolism that resemble the biochemical changes occurring in human ADPKD kidneys. These pathways are normally active in neonatal mouse kidneys until repressed around 3 weeks of age; however, they remain active following Pkd1 deletion. Together, this work describes the key parameters to accurately model the pathological and biochemical changes associated with ADPKD in a conditional mouse model. PMID- 27356572 TI - Comprehensive meta-analytical summary on human papillomavirus association with head and neck cancer. AB - An etiological role of high risk human papillomavirus (HPV) in the development of cervical cancer has been well established. Hence, attention of researchers has been focused on the role of HPV in pathogenesis of other malignancies, such as head and neck cancers. An analysis of epidemiological data on the prevalence of HPV infection among healthy people and patients with precancerous lesions and/or cancer is an important step in understanding the role of HPV in head and neck carcinogenesis. More and more data de-monstrate the impact of HPV infection on disease outcome. HPV-positive patients have been shown to have better responses to radiotherapy and better overall and disease-free survival than HPV-negative patients. This review presents data of the meta-analysis based on a large number of original studies on HPV prevalence in patients with precancerous lesions and in patients with oral, oropharyngeal and laryngeal cancers as well as findings on the impact of HPV infection on survival of these patients. PMID- 27356573 TI - Effect of copulation on potentially precancerous prostate lesions, serum testosterone and prolactin levels in rats. AB - The prostate is an exocrine reproductive gland that participates in ejaculation and it is prone to diseases, including cancer. AIM: In the pre-sent study, we assessed the long-term effects of copulation on the development of precancerous lesions in rats, and compared them with testosterone-induced prostatic lesions. MATERIALS AND METHODS: One group of Wistar males was given 10 copulatory sessions to one ejaculation with ovariectomized, hormone-primed females. Sessions occurred twice per week for a total of ten trials. A second group was exposed to females during the same trials, but physical contact was prevented. In addition, each group received a subcutaneous implant in the back either filled with testosterone propionate (T, 100 mg/kg) or empty. This resulted in four subgroups: 1) Control + No sex, 2) Control + Sex, 3) T + No sex and 4) T + Sex. Two days after the 10(th) trial all the males were sacrificed for prostate histo-logy (H&E) and hormone analysis (testosterone and prolactin). RESULTS: Males from the group Control + No sex expressed normal histo-logy. However, those in the groups Control + Sex and T + No sex expressed metaplasia and dysplasia in both the dorsolateral and ventral portions of the prostate, respectively. Interestingly, males from the group T + Sex expressed dysplasia in the dorsolateral prostate only, but not in the ventral prostate. CONCLUSIONS: These results indicate that constant copulation may facilitate the development of prostatic lesions in males with normal levels of testosterone. However, copulation induces less lesions in the ventral prostate of males treated with testosterone. PMID- 27356574 TI - Effectiveness of sodium dichloroacetate against glioma C6 depends on administration schedule and dosage. AB - BACKGROUND: Anticancer action of sodium dichloroacetate (DCA) could be related to its ability to activate oxidative phosphorylation leading to enhanced generation of reactive oxygen species and induction of apoptosis. On the other hand, activation of oxidative phosphorylation could promote tumor cell survival, in particular, via increased ATP synthesis. Such ambiguous effects of DCA could influence its anticancer effectiveness, depending on biological properties of a tumor, schedule of DCA administration and its dosage. The aim of the study was to analyze anticancer effect of DCA against glioma S6 in rats under conditions of different schedules of its administration and various dosages. MATERIALS AND METHODS: The study was carried out in Wistar rats with intracerebrally transplanted glioma S6 cells. Therapy with DCA was performed as follows: daily for 6 days starting from the second day after tumor cell transplantation (schedule I) or 7(th) day (schedule II) at a dose of 1.0 g/kg, or daily for 13 days starting from the second day at doses of 1.0; 1.5 or 4.5 g/kg (schedule III). An influence of hypoxia on anticancer effect of DCA was studied using hypoxic chambers where oxygen content was maintained at a level of 12.5-13% for 3 h after DCA administration to glioma S6 bearing rats. The state of mitochondrial electron transport chain components in tumor cells was studied using electron paramagnetic resonance. RESULTS: It has been shown that therapy with DCA using schedule I resulted in 15% decrease of animals life span (LS; < 0.05), while the use of schedule II had no effect on this index. Prolonged administration of DCA (schedule III) resulted in significant antitumor effect and increased LS of rats by 25.5% (p < 0.05). Under hypoxic conditions, treatment with DCA resulted in a significant increase of animal LS by 15-22%. Dosage of DCA had a moderate effect of its anticancer action. Maximal effect, an increase of LS by 34.5% (p < 0.05) was detected at a dose of 1.5 g/kg. It has been shown that anticancer activity of DCA under all studied conditions is not related to its influence on a functional state of tumor cell mitochondria. CONCLUSION: Anticancer effect of DCA significantly depends on a schedule of its administration; being administered at equal total dose, but dependent on the schedule DCA could cause ambiguous effects varying from tumor growth stimulation to significant anticancer activity. Under hypoxic conditions, anticancer efficacy of DCA against glioma S6 is significantly enhanced. PMID- 27356575 TI - Hepcidin as a possible marker in determination of malignancy degree and sensitivity of breast cancer cells to cytostatic drugs. AB - AIM: To investigate the role of hepcidin (Hepc) in the formation of cells malignant phenotype in vitro and its expression in the dyna-mics of growth of Walker-256 carcinosarcoma with different sensitivity to doxorubicin (Dox). MATERIALS AND METHODS: The cell lines used in the analysis included T47D, MCF-7, MDA-MB-231, MDA-MB-468, MCF/CP, and MCF/Dox. Hepc expression was studied by immunocytochemical method. "Free" iron content was determined by EPR spectroscopy. Determination of Hepc expression in homogenates of tumor tissue and in blood serum of rats with Dox-sensitive and -resistant Walker-256 carcinosarcoma was performed. RESULTS: It was found that Hepc levels in breast cancer (BC) cells with high degree of malignancy (MDA-MB-231, MDA-MB-468) and drug-resistant phenotype (MCF/CP, MCF/Dox) were by 1.5-2 times higher (p < 0.05) in comparison with sensitive and less malignant BC cells. The development of drug resistant phenotype in Walker-256 carcinosarcoma cells was accompanied by increasing of Hepc and "free" iron content (by 2.4 and 1.2 times, respectively). CONCLUSION: The data of in vitro and in vivo research evidenced on involvement of Hepc in formation of BC cells malignant phenotype and their resistance to Dox. PMID- 27356576 TI - Photocytotoxic effect of C60 fullerene against L1210 leukemic cells is accompanied by enhanced nitric oxide production and p38 MAPK activation. AB - AIM: To estimate the combined action of C60 fullerene and light irradiation on viability of L1210 leukemic cells, nitric oxide (NO) generation, p38 mitogen activated protein kinase (MAPK) activity and cell cycle distribution. METHODS: Cell viability was assessed by MTT test. Light-emitting diode lamp (lambda = 410 700 nm, 2.45 J/cm(2) ) was used for C60 fullerene photoexcitation. Nitrite level and NO-synthase activity were measured by Griess reaction and by conversion of L arginine to L-citrulline, respectively. p38 MAPK activity was assessed by Western blot analysis. Cell cycle distribution was determined by flow cytometry. RESULTS: It was shown that light irradiation of C60 fullerene-treated L1210 cells was accompanied by 55% decrease of their viability at 48 h of culture. Nitrite level measured as an index of reactive NO generation was increased at the early period after C60 fullerene photoexcitation due to activation of both constitutive and inducible NO-synthase isoforms. The simultaneous activation of p38 MAPK was detected. Accumulation of L1210 cells in sub-G1 phase of cell cycle was observed after C60 fullerene photoexcitation. CONCLUSION: Photoexcited C60 fullerene exerts cytotoxic effect, at least in part, through triggering production of reactive NO species and activation of p38 kinase apoptotic pathways in L1210 leukemic cells. PMID- 27356577 TI - Establishment and characterization of new breast and ovarian cancer cell lines as a model for studying cellular plasticity in vitro. AB - AIM: To compare biological properties of primary tumor cells isolated from malignant effusion of cancer patients with the same cells of permanent lines established during their long-term cultivation in vitro and to assess the impact of phenotypic conversion that was caused by changes in their microenvironment on their behavioral characteristics. MATERIALS AND METHODS: The study was performed on primary cell cultures from pleural effusion or ascites of breast and ovarian cancer and permanent cell lines derived from them, namely permanent ovarian cancer cell line I, permanent ovarian cancer cell line II and permanent breast cancer cell line I. Biological characteristics were studied using standard cell culture methods and immunocytochemical assays. RESULTS: Three new cell lines were established from breast and ovarian cancer and cell morphology, migration activity, the kinetics of growth, colony forming activity in semisolid agar and sensitivity to anticancer drug were examined. These characteristics were compared with those of the primary tumor cells. It has been shown that among the primary tumor cells from malignant effusion, cells with mese-nchymal characteristics were the most prevalent. Cultivation of primary cancer cells in vitro leads to a phenotypic change of their population: it becomes more homogeneous in morphology with predominantly epithelial-like cells. Also, later after a number of cell doublings in vitro, the cell population changes to include cells primarily with immunophenotypic properties characteristic of epithelial cells. These changes include increase in number of E-cadherin-positive cells and a decrease in number of vimentin and alpha- smooth muscle actin-positive cells. It was found that significant changes in expression of epithelial-mesenchymal transition associated proteins in cells during their cultivation in vitro in new microenvironment are accompanied by a rapid change in their sensiti-vity to anticancer drugs. CONCLUSIONS: The new breast and ovarian cancer cell lines were established and characterized. The induction of phenotypic transdifferentiation in malignant cells from pleural effusion and ascites can be an important approach for suppressing the progression of neoplastic process. PMID- 27356578 TI - Differential expression of CD150/SLAMF1 in normal and malignant B cells on the different stages of maturation. AB - Within B-cell lineage cell surface receptor CD150/SLAMF1 is broadly expressed starting from pre-B cells with upregulation toward plasma cells. However, expression of CD150 is rather limited on the surface of malignant B cells with the block of differentiation at the different stages of maturation. The aim of our work was to explore CD150 expression both on protein and mRNA levels with the emphasis on CD150 isoforms in malignant B-cell lines at the different stages of maturation in comparison with their normal B cell counterparts. MATERIALS AND METHODS: Studies were performed on normal tonsillar B-cell subpopulations, B lymphoblastoid cell lines, malignant B-cell lines of different origin, including pre-B acute lymphoblastic leukemia, Burkitt's lymphoma, Hodgkin's lymphoma, and multiple myeloma. Protein CD150 expression was assessed by western blot analysis and the expression level of CD150 isoforms was evaluated using qRT-PCR. RESULTS: Despite the similar CD150 expression both on mRNA and protein levels in normal B cell subsets and B-lymphoblastoid cell lines, malignant B-cell lines demonstrated substantial heterogeneity in CD150 expression. Only Hodgkin's lymphoma cell lines, Burkitt's lymphoma cell lines BJAB and Raji, and also pre-B cell line BLIN 1 expressed CD150 protein. At the same time total CD150 and mCD150 mRNA was detected in all studied cell lines excluding pre-B cell line REH. The minor sCD150 isoform was found only in Hodgkin's lymphoma cell lines and Burkitt's lymphoma cell line Raji. The nCD150 isoform was broadly expressed in tested B cell lines with exception of REH and Daudi. CONCLUSION: Malignant B-cell lines at the different stages of maturation only partially resemble their normal counterparts by CD150 expression. In malignant B-cell lines, CD150 expression on mRNA level is much broader than on protein level. CD150 isoforms are differentially expressed in normal and malignant B cells with predominant expression of mCD150 isoform. PMID- 27356579 TI - Radioprotective properties of sodium humate in radiation-induced mutagenesis in cultured lymphocytes of thyroid cancer patients. AB - To investigate the effect of sodium humate on the level of cytogenetic damage in culture of lymphocytes of patients with thyroid cancer after gamma-irradiation. MATERIALS AND METHODS: Metaphase analysis of chromosome aberrations in cultured peripheral blood lymphocytes of 10 individuals with thyroid cancer was performed after irradiation of lymphocytes in vitro at a dose of 1 Gy from (137)Cs source at the early G0 phase of cell cycle. Sodium humate was added to cell culture for 30 +/- 15 min after phytohemagglutinin stimulation at concentrations of 10 and 100 MUg/ml. RESULTS: Sodium humate exhibited antimutagenic properties. The preparation at a concentration of 10 MUg/ml was more effective than at a concentration of 100 MUg/ml, reducing the average incidence of radiation-induced chromosome aberrations by 51.88 and 38.77%, respectively. The most pronounced antimutagenic effect of sodium humate was the reduction of the frequency of chromosomal type aberrations, however, such efficiency varied between individual patients with thyroid cancer. CONCLUSIONS: Sodium humate could be considered as a potential therapeutic modifier of radiation damage. PMID- 27356580 TI - Detection of NOTCH1 c.7541_7542delCT mutation in chronic lymphocytic leukemia using conventional and real-time polymerase chain reaction. AB - To evaluate real-time polymerase chain reaction (PCR) assay system for detection of NOTCH1 c.7541_754delCT mutation in chronic lymphocytic leukemia (CLL) patients. MATERIAL AND METHODS: A total of 325 CLL patients were included in the study. Screening for NOTCH1 c.7544_7545delCT was performed using conventional PCR based amplification refractory mutation system (ARMS) method. All 33 samples harboring c.7544_7545delCT allele and 5 negative cases as control were submitted to real-time PCR. RESULTS: Specificity and sensitivity of two PCR techniques were comparable. NOTCH1 c.7544_7545delCT mutation was found by ARMS in 10.1% of CLL patients, which is consistent with the data of other studies. However, the results of ARMS PCR in a minority of cases (2.15%) were doubtful and required reinvestigation. Real-time PCR, being less time-consuming, showed advantage in the assessment of the amplification's specificity (using the melting curve analysis). It also allows the quantitative assessment of NOTCH1-mutated clone. CONCLUSION: NOTCH1 c.7544_7545delCT mutation resulting in removal of the C terminal PEST domain, deregulation of NOTCH1-dependent signaling pathways, has negative influence on prognosis of CLL and efficiency of therapy with anti-CD20 monoclonal antibodies. Real-time PCR allows the fast and reliable detection of c.7544_7545delCT mutation and can be used for the screening of this molecular lesion in CLL patients. PMID- 27356581 TI - The level of IgG antibodies reactive to TF, Tn and alpha-Gal polyacrylamide glycoconjugates in breast cancer patients: relation to survival. AB - BACKGROUND: The serum levels of IgG antibodies reactive to glycoconjugates (TF, Tn and alphaGal) were found to be associated with prognosis of gastrointestinal cancer patients. AIM: To study the relation between the levels of serum antibodies to TF-pAA, Tn-PAA and alphaGal-PAA polyacrylamide-based glycoconjugates and survival in breast cancer. MATERIALS AND METHODS: The preoperative level of IgG antibodies was analysed in the serum of patients (n = 59) using ELISA with polyacrylamide-glycoconjugates namely, TF-pAA (amide-type), and ethanolamide-conjugates Tn-PAA and alphaGal-PAA. Survival rate and hazard ratio (HR) were assessed by the Kaplan - Meier method and Cox univariate analysis in different pathomorphological groups. RESULTS: Significantly better survival was observed in patients with an increased level of anti-TF-pAA antibodies both for all patients in total and groups in stages II-III; N1-2 and G3 (p = 0.008 0.021, HR = 0.18-0.23, mean survival time in months 164-186 vs 69-121). A trend to worse survival was observed in increased level of anti-Tn IgG (stages II-III) and anti-alphaGal IgG (G3): p = 0.075, HR = 2.49 and p = 0.066, HR = 3.27, respectively. CONCLUSION: The method for the determination of circulating anti-TF pAA IgG may be a useful supplement in long-term prognostic assessment of patients with breast cancer. PMID- 27356582 TI - Clinicopathological features of nonspecific invasive breast cancer according to its molecular subtypes. AB - The aim of the present study was to investigate the clinical and morphological features of nonspecific invasive breast cancer according to its molecular subtypes. MATERIALS AND METHODS: 163 women with nonspecific invasive breast cancer (T1-4N0-3M0) were included in the present study. Luminal A type of breast cancer was detected in 101 women, luminal B type - in 23 women, overexpression of HER2/neu was identified in 14 women and triple-negative cancer - in 25 women. RESULTS: The study revealed that various molecular subtypes of breast cancer differ in the morphological structure, the expression characteristics of the primary tumor and the rate of lymphogenous and hematogenous metastasis. Lymphogenous metastases were more frequently (in 71%) detected in HER2/neu overexpressing breast cancer than in luminal A (41%), luminal B (39%) and triple negative tumors (40%). Hematogenous metastasis did not depend on the morphological structure of carcinoma infiltrative component, the state of tumor stroma as well as the proliferative activity in all the investigated groups. CONCLUSION: The revealed clinicopathological characteristics of different molecular subtypes of invasive breast cancer allow to predict the possible outcome of the disease and select personalized treatment strategy for patients more reasonably. PMID- 27356583 TI - Materials of International scientific conference "Integrated clinical and pathogenetic approaches in diagnosis and therapy of cancer", June 13-15, 2016, Kyiv, Ukraine. PMID- 27356584 TI - Daniil F. Gluzman (on the 80(th) birth anniversary). AB - In June 2016, Professor Daniil Fishelevich Gluzman, well-known Ukrainian oncohematologist, celebrates his 80(th) anniversary. PMID- 27356585 TI - Nikolai Fedorovich Gamaliya (1932-2016). AB - Professor Nikolai Fedorovich Gamaliya, well-known scientist in the field of laser biomedical research, biophysicist, authority in experimental oncology, Laureate of the State Prize in Science and Techno-logy of Ukraine, Head of the Department of Biological Effects of Ionizing and Non-Ionizing Radiation of R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the National Academy of Sciences (NAS) of Ukraine died on June 14, 2016 at the age of 83. PMID- 27356586 TI - Synergistic Chemo-Photothermal Therapy of Breast Cancer by Mesenchymal Stem Cell Encapsulated Yolk-Shell GNR@HPMO-PTX Nanospheres. AB - Mesenchymal stem cells (MSCs) have attracted increasing attention as vehicles for cancer treatment. Herein, MSC-based synergistic oncotherapy strategy is presented for the first time. To achieve this goal, yolk-shell structured gold nanorod embedded hollow periodic mesoporous organosilica nanospheres (GNR@HPMOs) with high paclitaxel (PTX) loading capability and excellent photothermal transfer ability upon near-infrared (NIR) light irradiation are first prepared. Cytotoxicity and migration assays show that the viability and tumor-homing capability of MSCs are well-retained after internalization of high content of PTX loaded GNR@HPMOs (denoted as GNR@HPMOs-PTX). In vitro experiments show the GNR@HPMOs-PTX loaded MSCs (GNR@HPMOs-PTX@MSCs) possess synergistic chemo photothermal killing effects for breast cancer cells. Also, photoacoustic imaging shows that the MSCs can improve dispersion and distribution in tumor tissue for GNR@HPMOs-PTX after intratumoral injection. In vivo experiments in breast cancer model of nude mice further demonstrate that the GNR@HPMOs-PTX@MSCs significantly inhibit tumor growth, suggesting their great potential for synergistic therapy of cancer. PMID- 27356587 TI - Data-Driven Approach To Determine Popular Proteins for Targeted Proteomics Translation of Six Organ Systems. AB - Amidst the proteomes of human tissues lie subsets of proteins that are closely involved in conserved pathophysiological processes. Much of biomedical research concerns interrogating disease signature proteins and defining their roles in disease mechanisms. With advances in proteomics technologies, it is now feasible to develop targeted proteomics assays that can accurately quantify protein abundance as well as their post-translational modifications; however, with rapidly accumulating number of studies implicating proteins in diseases, current resources are insufficient to target every protein without judiciously prioritizing the proteins with high significance and impact for assay development. We describe here a data science method to prioritize and expedite assay development on high-impact proteins across research fields by leveraging the biomedical literature record to rank and normalize proteins that are popularly and preferentially published by biomedical researchers. We demonstrate this method by finding priority proteins across six major physiological systems (cardiovascular, cerebral, hepatic, renal, pulmonary, and intestinal). The described method is data-driven and builds upon the collective knowledge of previous publications referenced on PubMed to lend objectivity to target selection. The method and resulting popular protein lists may also be useful for exploring biological processes associated with various physiological systems and research topics, in addition to benefiting ongoing efforts to facilitate the broad translation of proteomics technologies. PMID- 27356588 TI - Screening targeted testis-specific genes for molecular assessment of aberrant sperm quality. AB - Teratospermia is a heterogeneous and complex disorder, which is closely associated with male fertility. Genes and gene products associated with teratospermia may serve as targeted biomarkers that help understand the underlying mechanisms of male infertility; however, systematic information on the subject remains to be elucidated. The present study performed a comparative bioinformatics analysis to identify biomarkers associated with sperm quality, particular focusing on testis-specific biomarkers. A stepwise screening approach identified 1,085 testis/epididymis-specific genes and 3,406 teratospermia associated genes, resulting in 348 testis-specific genes associated with aberrant sperm quality. These genes were functionally associated with the reproduction process. Gene products corresponding to heat shock protein family A (Hsp70) member 4 like (HSPA4L) and phosphoglycerate kinase 2 were characterized at the cellular level in human testes and ejaculated spermatozoa. HSPA4L expression in sperm was revealed to be associated with sperm quality. The present study provided a novel insight into the understanding of sperm quality, and a potential method for the diagnosis and assessment of sperm quality in the event of male infertility. PMID- 27356589 TI - Influenza viral vector based Brucella abortus vaccine: a novel vaccine candidate for veterinary practice. PMID- 27356590 TI - Diabetes treatment and hypoglycaemic episodes in elderly patients at nursing homes in Uppsala County. AB - AIM: The aim of this study was to examine the situation for elderly patients with diabetes living in nursing homes with regard to diabetes treatment, clinical variables, and vascular complications associated with diabetes. A second aim was to evaluate if the patients were at risk of hypoglycaemia. METHODS: This was a cross-sectional study including diabetes patients from all 30 nursing homes in Uppsala County, Sweden. Current antidiabetic medications, HbA1c, hypoglycaemic events, and diabetes complications were registered from the medical records. The patients were stratified into a general group and divided into three groups according to HbA1c (<52, 52-73, and >73 mmol/mol). RESULTS: Of 1,350 individuals, 218 patients were identified with diabetes mellitus. The diabetes duration was 11.2 +/- 9.4 years and their serum HbA1c concentration 56.0 +/- 1.2 mmol/mol. Hypoglycaemic events were reported in 24% of the diabetic individuals, and 43.1% of them had HbA1c <52 mmol/mol (mean value 44.0 +/- 1.1 mmol/mol). Of these, 36% were taking antidiabetic drugs. Another 35.8% of the patients had HbA1c values between 52-73 mmol/mol (mean value 60.0 +/- 1.1 mmol/mol), and 82% of these patients were taking antidiabetic drugs. Almost 80% of the diabetic patients had either micro- or macrovascular complications, with diabetes duration as an association for both micro- or macrovascular complications and hypoglycaemic events. CONCLUSIONS: A reduction of the use of antidiabetic drugs with follow-up of HbA1c level should be considered, especially for multimorbid elderly patients with low HbA1c and hypoglycaemia. PMID- 27356591 TI - Bacteria of leg atheromatous arteries responsible for inflammation. AB - BACKGROUND: Ischaemia of the lower limbs is frequently followed by inflammation and, in advanced cases, necrosis of peripheral tissues. Whether this is caused by arterial hypoperfusion only or by the presence of bacteria in the arterial walI as well remains unclear. The aim of the study was to prove the presence and source of bacteria in arterial specimens and evaluate their chemotactic properties resulting in the formation of periarterial cellular infiltrates. MATERIALS AND METHODS: Bacterial culture and testing for 16sRNA were performed in fragments of popliteal artery harvested from amputated limbs. Carotid artery plaques served as controls. Fragments of arteries were transplanted into scid mice to evaluate their chemotactic activity for macrophages. RESULTS: a) higher prevalence of isolates and 16sRNA in atherosclerotic popliteal than carotid arteries, b) high density of plaque and periarterial infiltrates and mRNA level for pro-inflammatory cytokines in popliteal arteries, c) prevalent microbes were Staphylococcus aureus, S. epidermidis and Enterococci, d) foot skin and arterial bacterial phenotypes and DNA revealed evident similarities, and e) more intensive mouse macrophage accumulation in popliteal than carotid implants into scid mice. CONCLUSIONS: The presence of bacteria in the lower limb arterial wall was documented. They may predispose to inflammation secondary to ischaemic changes. PMID- 27356592 TI - Falls, fractures and bone density in Parkinson's disease - a cross-sectional study. AB - AIM: Evidence suggests that falls and associated bone fractures are more frequent in patients suffering from Parkinson's disease (PD) than in the general population. In this cross-sectional study we evaluated the clinical and biochemical characteristics that are associated to falls, fractures and bone health in a population of PD subjects. MATERIALS AND METHODS: Forty-two consecutive subjects suffering from idiopathic PD (mild-to-moderate severity) with/without falls in the previous year were included. They were characterized as regards functional independence, balance, fear of falling, bone density (ultrasound densitometry) and plasma levels of vitamin D. Twenty-one age- and sex matched healthy subjects were evaluated as controls. RESULTS: We detected a greater degree of osteoporosis in PD subjects as compared to controls, more pronounced in males than in females (Z-score: M -3.8 +/- 1.6, F -2.28 +/- 0.92, p = 0.0006). A positive correlation was found between independence levels and bone density or vitamin D levels. Twenty seven patients (64%) reported falls in the previous year. These were associated to post-traumatic fractures in 16 subjects (59% of fallers). Women fell more than men (fallers: 20 F/7 M; non fallers: 4 F/11 M, chi2 test p = 0.02), although the occurrence of post-traumatic fractures among fallers did not differ between sexes (F 11/9, M 5/2, chi2 test p > 0.05). Fallers with post-traumatic fractures showed higher degrees of motor impairment. CONCLUSIONS: These findings confirm that falls and osteoporosis represent major health issues in PD, already in the middle stages of disease. PMID- 27356593 TI - [Potential immunomodulatory and antiinflammatory mechanisms of probiotics]. AB - The number of preclinical and clinical studies showing efficacy of probiotics in the treatment and prophylaxis of certain diseases, e.g. diarrhoea of various origin, irritable bowel syndrome, inflammatory bowel disease, allergies, hypercholesterolemia, bacterial vaginosis, and colorectal cancer, is increasing. These health benefits are often species and strain specific. This article provides an overview of available knowledge about the supposed mechanisms of probiotic microorganisms action focusing in particular on the interaction between probiotic and host cells. One of the results of this interaction is induction of pro- or anti-inflammatory immune response in the macroorganism. Detailed knowledge of the signalling pathways involved in the communication between bacterial and human cells can find application in the selection of optimal probiotics for the targeted treatment of selected diseases. Additional possibilities for their use in clinical practice are provided by genetic manipulation of probiotic microorganisms. KEY WORDS: probiotics inflammation signalling pathways immunomodulation genetic manipulation. PMID- 27356594 TI - [Mice lacking individual molecular forms of cholinesterases]. AB - Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) represent a small family of enzymes called cholinesterases. These enzymes are in the organisms either soluble or anchored through anchoring proteins collagen Q (ColQ) and proline-rich membrane anchor (PRiMA). Knowledge of molecular biology and genetics of cholinesterase and their anchoring proteins resulted in the preparation of mutant mice with the absence of different molecular forms of cholinesterases. So far a number of mutant mice were prepared with a genetic modification on the genes encoding cholinesterases or anchoring proteins. The mice with mutation in the genes encoding the cholinesterases are: the mice with the absence of AChE, mice with the absence of BChE, mice with a deletion of exon 5 and 6 in the AChE gene and mice with the absence of AChE in muscles. The mice with a mutation in the genes encoding anchoring proteins include the mice with the absence of AChE and BChE anchored by ColQ and mice with the absence of AChE and BChE anchored by PRiMA. The study of adaptation changes results from the absence of cholinesterases led to the enrichment of existing knowledge about cholinesterases and the cholinergic nervous system. KEY WORDS: absence of cholinesterases mutant mice acetylcholinesterase butyrylcholinesterase. PMID- 27356595 TI - [Oral adverse drug reactions in various medications]. AB - The goal of the article is to emphasize the fact that adverse drug effects which are manifested in the oral cavity are exhibited in two ways. This may occur either after a direct application of the preparation used in dental practice, or due to the application of the drug for nondental purpose. That is why the adverse effects of medicines prescribed by various clinical specialists should be considered by stomatologists in their own clinical practice. Examples are reported of some serious drug adverse effects manifested on the oral mucous membrane and gum. Attention is paid to the classes which reveal adverse reactions after applications as local anaesthetics, corticosteroids and others. KEY WORDS: oral adverse drug reactions local anaesthetics corticosteroids. PMID- 27356596 TI - Phenolic compounds of the genus Iris plants (Iridaceae). AB - This article presents the results of testing of phenolic compounds (flavonoids, isoflavonoids, xanthones, phenolcarboxylic acids, tannins, coumarins, etc.) in the rhizomes of four Iris species (Iris sibirica L., Iris pseudacorus L., Iris imbricata Lindl., Iris hungarica Waldst. et Kit.). With the use of paper and thin layer chromatography, fifteen phenolic compounds were identified: gallic, coumaric, cinnamic, chlorogenic, neochlorogenic, ferulic, caffeic acids; kaempferol, quercetin, hispidulin, daidzein, genistein, formononetin, mangiferin and isomangiferin. Quantitative contents of flavonoids (1.2-3.7%), hydroxycinnamic acids (0.6-6.5%), gamma-pyrones (0.01-0.8%), tannins (6-14%), isoflavonoids (1-2%), polyphenolic compounds (up to 3%) in the rhizomes of the Iris species were determined. Chosen plants belong to natural flora and have been often cultivated. However, this phytochemical analysis for the main groups of the biologically active substances shows a perspective use of the Iris species in medicine. KEY WORDS: Iris species Iridaceae phenolic compounds chromatography qualitative analysis quantitative contents. PMID- 27356597 TI - [The evaluation of the prevalence of constipation at the Centre of clinical gerontology]. AB - Constipation is a disease which increases in the senior population and is a common complication for hospitalised patients. Among the risk factors are age, female gender, immobility, diet, fluid intake and polypharmacotherapy. The aim of the study was to analyse the prevalence of constipation according to the used drugs and known risk factors in a population with a high prevalence of constipation. In the department of clinical gerontology, observational prevalence point study was performed using a questionnaire involving 100 patients based on the patients subjective perception of constipation. Prevalence of constipation was determined according to the drug categories and individual drugs, gender, age, mobility, diagnosis, diet and fluid intake. There were 59 patients who suffered from constipation. A high prevalence of constipation was associated with the diet, the principal diagnosis, and mainly the use of drugs. Among the drugs associated with constipation were the calcium channel blockers of 21 patients out of 28, HMG-CoA reductase inhibitors of 22 patients out of 30, drugs for the treatment of increased urinary frequency and incontinence of 6 patients out of 6 and bisoprolol of 10 patients out of 11. Hospitalisation of seniors is connected with the high prevalence of constipation that is increased by the use of drugs that influence constipation. A change in the therapeutic value of drugs should be taken into consideration during the pharmacotherapy of this group of patients. KEY WORDS: constipation risks factors for constipation drug-induced constipation. PMID- 27356598 TI - Treatment of renal ANCA-associated vasculitides. AB - Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of small vessel vasculitides which commonly affect the kidneys, manifesting as rapidly progressive glomerulonephritis. In this review, we present different treatment methods (e.g. cyclophosphamide, rituximab, plasma exchange) used for remission induction and maintenance in renal AAV. We also discuss treatment options in relapsing and refractory disease and for patients with end-stage renal disease due to AAV. In addition, we enumerate the various risk factors associated with relapsing and refractory disease, quality of life impairment and decreased renal and patient survival in AAV. Finally we present information on new, potentially applicable agents which can further help modify the disease course, thereby leading to increased patient survival. PMID- 27356599 TI - Involvement of regulatory T cells and selected cytokines in the pathogenesis of bronchial asthma. AB - Asthma pathogenesis is complex and involves the interplay of many factors and actions. Airway inflammation in allergic asthma is characterized by an exaggerated activation of T helper type 2 cells, IgE production and infiltration and activation of eosinophils. The results of studies conducted in recent years indicate that the deficit of naturally occurring Foxp3+CD25+CD4+ and Foxp3+CD25+CD8+ regulatory T cells and type 1 regulatory T cells plays a pivotal role in the development of this disease. Moreover, numerous studies have provided convincing evidence that a decrease in IL-10 production and an increase in IL-17 production have an important place in the pathophysiology of asthma. TGF-beta is another important cytokine involved in this disease. TGF-beta has a paradoxical status in relation to asthma pathogenesis because it seems to play a role in both suppressing and promoting asthma development. This review discusses briefly clinical and experimental data concerning the involvement of T regulatory cells and IL-10, IL-17 and TGF-beta in the pathogenesis of asthma. PMID- 27356600 TI - The role of serine proteases in the pathogenesis of bacterial infections. AB - An increasing resistance of pathogenic bacterial species has been considered as one of the major health problems worldwide. The discovery of novel protein targets and development of effective anti-bacterial therapeutics is of high need since for some extremely resistant pathogens we are simply left unarmed. One of new promising therapeutic strategy is the application of specific inhibitors targeting bacterial serine proteases. Pathogenic microorganisms secrete abroad range of hydrolases, including serine proteases which lead to activation of various virulence factors. Herein, we review the specific bacteria serine proteases which have an influence on pathogenicity of bacterial infection as well as we introduce the reader with a brief history of the subject. PMID- 27356602 TI - Misregulation of iron homeostasis in amyotrophic lateral sclerosis. AB - Iron is essential for all mammalian cells, but it is toxic in excess. Our understanding of molecular mechanisms ensuring iron homeostasis at both cellular and systemic levels has dramatically increased over the past 15 years. However, despite major advances in this field, homeostatic regulation of iron in the central nervous system (CNS) requires elucidation. It is unclear how iron moves in the CNS and how its transfer to the CNS across the blood-brain and the blood cerebrospinal fluid barriers, which separate the CNS from the systemic circulation, is regulated. Increasing evidence indicates the role of iron dysregulation in neuronal cell death observed in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). ALS is a progressive neurodegenerative disorder characterized by selective cortical czynand spinal motor neuron dysfunction that results from a complex interplay among various pathogenic factors including oxidative stress. The latter is known to strongly affect cellular iron balance, creating a vicious circle to exacerbate oxidative injury. The role of iron in the pathogenesis of ALS is confirmed by therapeutic effects of iron chelation in ALS mouse models. These models are of great importance for deciphering molecular mechanisms of iron accumulation in neurons. Most of them consist of transgenic rodents overexpressing the mutated human superoxide dismutase 1 (SOD1) gene. Mutations in the SOD1 gene constitute one of the most common genetic causes of the inherited form of ALS. However, it should be considered that overexpression of the SOD1 gene usually leads to increased SOD1 enzymatic activity, a condition which does not occur in human pathology and which may itself change the expression of iron metabolism genes. PMID- 27356601 TI - From tyrosine to melanin: Signaling pathways and factors regulating melanogenesis. AB - Melanins are natural pigments of skin, hair and eyes and can be classified into two main types: brown to black eumelanin and yellow to reddish-brown pheomelanin. Biosynthesis of melanins takes place in melanosomes, which are specialized cytoplasmic organelles of melanocytes - dendritic cells located in the basal layer of the epidermis, uveal tract of the eye, hair follicles, as well as in the inner ear, central nervous system and heart. Melanogenesis is a multistep process and begins with the conversion of amino acid L-tyrosine to DOPAquinone. The addition of cysteine or glutathione to DOPAquinone leads to the intermediates formation, followed by subsequent transformations and polymerization to the final product, pheomelanin. In the absence of thiol compounds DOPAquinone undergoes an intramolecular cyclization and oxidation to form DOPAchrome, which is then converted to 5,6-dihydroksyindole (DHI) or 5,6-dihydroxyindole-2-carboxylic acid (DHICA). Eumelanin is formed by polymerization of DHI and DHICA and their quinones. Regulation of melanogenesis is achieved by physical and biochemical factors. The article presents the intracellular signaling pathways: cAMP/PKA/CREB/MITF cascade, MAP kinases cascade, PLC/DAG/PKCbeta cascade and NO/cGMP/PKG cascade, which are involved in the regulation of expression and activity of the melanogenesis-related proteins by ultraviolet radiation and endogenous agents (cytokines, hormones). Activity of the key melanogenic enzyme, tyrosinase, is also affected by pH and temperature. Many pharmacologically active substances are able to inhibit or stimulate melanin biosynthesis, as evidenced by in vitro studies on cultured pigment cells. PMID- 27356603 TI - Radioprotectors in radiotherapy - advances in the potential application of phytochemicals. AB - Radiotherapy, in addition to chemotherapy, is currently the primary method of cancer treatment based on destruction of malignant cells by ionizing radiation. Unfortunately, it also affects normal cells, which is associated with negative consequences for a patient. Radioprotectors are compounds used to prevent/protect the non-tumor cells from the harmful effects of radiation. To play their role these compounds should meet several criteria; among others, they should significantly protect normal cells from radiation without changing the tumor cell radiosensitivity. In general, agents used to alter normal tissue toxicity from radiation can be broadly divided into three categories based on timing of delivery in relation to radiation: chemical radioprotectors, mitigators, and treatment. These groups include a diverse range of synthetic compounds in terms of their structure and protective mechanisms. The aminoradiothiol amifostine is the only radioprotectant approved in clinical application. However, its use is limited due to toxicity concerns (it may cause hypotension). Natural compounds, derived from plants, meet all criteria of the ideal radioprotector. They exert their protective actions against adverse effects of ionizing radiation by several mechanisms. Plant compounds that show radioprotective activity include flavonoids and phenolic acids, stilbenes, lycopene, alkaloids, peptides, polysaccharides, and phytohormones. Garlic, green tea, apples, citrus, and ginger are examples of constituents of the human diet that contain radioprotective substances. PMID- 27356604 TI - PPARalpha induced NOS1 phosphorylation via PI3K/Akt in guinea pig antral mucous cells: NO-enhancement in Ca(2+)-regulated exocytosis. AB - A PPARalpha (peroxisome proliferation activation receptor alpha) agonist (GW7647) activates nitric oxide synthase 1 (NOS1) to produce NO leading to cGMP accumulation in antral mucous cells. In this study, we examined how PPARalpha activates NOS1. The NO production stimulated by GW7647 was suppressed by inhibitors of PI3K (wortmannin) and Akt (AKT 1/2 Kinase Inhibitor, AKT-inh), although it was also suppressed by the inhibitors of PPARalpha (GW6471) and NOS1 (N-PLA). GW7647 enhanced the ACh (acetylcholine)-stimulated exocytosis (Ca(2+) regulated exocytosis) mediated via NO, which was abolished by GW6471, N-PLA, wortmannin, and AKT-inh. The Western blotting revealed that GW7647 phosphorylates NOS1 via phosphorylation of PI3K/Akt in antral mucous cells. The immunofluorescence examinations demonstrated that PPARalpha existing with NOS1 co localizes with PI3K and Akt in the cytoplasm of antral mucous cells. ACh alone and AACOCF3, an analogue of arachidonic acid (AA), induced the NOS1 phosphorylation via PI3K/Akt to produce NO, which was inhibited by GW6471. Since AA is a natural ligand for PPARalpha, ACh stimulates PPARalpha probably via AA. In conclusion, PPARalpha activates NOS1 via PI3K/Akt phosphorylation to produce NO in antral mucous cells during ACh stimulation. PMID- 27356605 TI - Megalo-type alpha-1,6-glucosaccharides induce production of tumor necrosis factor alpha in primary macrophages via toll-like receptor 4 signaling. AB - The term "megalo-saccharide" is used for saccharides with ten or more saccharide units, whereas the term "oligo-saccharide" is used for saccharides containing fewer than ten monosaccharide units. Megalo-type alpha-1,6-glucosaccharide (M-IM) is a non-digestible saccharide and not utilized by intestinal bacteria, suggesting that ingested M-IM may encounter ileum Peyer's patches that contains immune cells such as macrophages. Macrophages are responsible for antigen incorporation and presentation during the initial step of immune responses. We investigated whether M-IMs modulate macrophage functions such as cytokine production, nitric oxide production, cell viability, and phagocytosis. Primary macrophages collected from the rats were cultured with the existence of M-IM or lipopolysaccharides (LPS). M-IM and LPS induced the production of tumor necrosis factor alpha (TNFalpha), interleukin 6 (IL6), and nitric oxide in the primary macrophages. The gene expression profile of inflammatory factors including TNFalpha, IL6, and ILlbeta in M-IM-stimulated cells was similar to that of LPS stimulated cells. The M-IM did not affect phagocytosis in the primary macrophages. The M-IM-induced TNFalpha production was suppressed in the cells treated with a tolllike receptor 4 (TLR4) inhibitor called TAK-242. In conclusion, the M-IM modulates cytokine expression via TLR4 signaling and may play a role in the modulation of immune responses. PMID- 27356606 TI - The selective distribution of LYVE-1-expressing endothelial cells and reticular cells in the reticulo-endothelial system (RES). AB - LYVE-1, a receptor molecule for hyaluronan, is expressed in the lymphatic endothelium, blood sinus endothelium, and certain macrophage lineages. The present immunohistochemical study revealed a broader distribution of LYVE-1 in vascular endothelial cells of the murine lung, adrenal gland, and heart as well as the liver and spleen. In addition, sinus reticular cells-including sinuslining cells-in the medulla of the lymph node also intensely expressed LYVE-1. Ultrastructurally, immuno-gold particles for LYVE-1 were localized on the entire length of plasma membrane in all cell types. Most of these LYVE-1-expressing cells had previously been classified as the reticuloendothelial system (RES) specialized for eliminating foreign particles. An LPS stimulation decreased the LYVE-1 expression in macrophages but elevated the expression at mRNA and protein levels in the liver and lung, major organs for the elimination of blood-born waste substances. LYVE-1-expressing endothelial cells in these organs participated in the endocytosis of exogenous particles, and the uptake ability was conspicuously enhanced by the LPS challenge. Although the expression of the degrading enzyme, hyaluronidase, was generally low in the LYVE-1-expressing cells, they were topographically associated with a dense distribution of macrophages possessing hyaluronidase activities in each tissue. These findings suggest that the LYVE-1-expressing cells might be involved in the uptake of hyaluronan and other waste products as well as foreign particles circulating in the blood and lymph while participating in the subsequent degradation in relay with adjacent macrophage populations. PMID- 27356607 TI - Vitamin D3 analog maxacalcitol (OCT) induces hCAP-18/LL-37 production in human oral epithelial cells. AB - Maxacalcitol (22-oxacalcitriol: OCT) is a synthetic vitamin D3 analog with a limited calcemic effect. In this study, we investigated whether OCT increases the production of LL-37/CAP-18, a human cathelicidin antimicrobial peptide, in human gingival/oral epithelial cells. A human gingival epithelial cell line (Ca9-22) and human oral epithelial cell lines (HSC-2, HSC-3, and HSC-4) exhibited the enhanced expression of LL-37 mRNA upon stimulation with OCT as well as active metabolites of vitamins D3 and D2. Among the human epithelial cell lines, Ca9-22 exhibited the strongest response to these vitamin D-related compounds. OCT induced the higher production of CAP-18 (ng/mL order) until 6 days time dependently in Ca9-22 cells in culture. The periodontal pathogen Porphyromonas gingivalis was killed by treatment with the LL-37 peptide. These findings suggest that OCT induces the production of hCAP-18/LL-37 in a manner similar to that induced by the active metabolite of vitamin D3. PMID- 27356608 TI - Developmental changes in primary cilia in the mouse tooth germ and oral cavity. AB - The primary cilium, a sensory apparatus, functions as both a chemical and mechanical sensor to receive environmental stimuli. The present study focused on the primary cilia in the epithelialmesenchymal interaction during tooth development. We examined the localization and direction of projection of primary cilia in the tooth germ and oral cavity of mice by immunohistochemical observation. Adenylyl cyclase 3 (ACIII)-immunolabeled cilia were visible in the inner/outer enamel epithelium of molars at the fetal stage and then conspicuously developed in the odontoblast layer postnatally. The primary cilia in ameloblasts and odontoblasts-shown by the double staining of acetylated tubulin and gamma tubulin-were regularly arranged from postnatal Day12, projecting apart from each other. The periodontal ligament possessed ACIII-positive cilia, which gathered on both sides of the dentin/cement and alveolar bone in postnatal days. In the oral cavity, numerous long primary cilia immunoreactive for ACIII were condensed at subepithelial stromal cells in the oral processes in fetuses, while postnatally a small number of short cilia were dispersed throughout the stroma of the oral cavity. These findings suggest that the primary cilia showing stage- and regionspecific morphology are involved in the epithelial-mesenchymal interaction during tooth development via mechano- and/or chemoreception for growth factors. PMID- 27356609 TI - Steroid changes adipokine concentration in the blood and bone marrow fluid. AB - Our previous study has shown that plasminogen activator inhibitor 1 (PAI-1) gene expression and secretion from bone marrow adipocytes increased markedly with dexamethasone administration. The purpose of the present study was to measure the secretion of various adipokines from human bone marrow and blood, and investigate how adipokine secretion changes in a steroid environment. Human blood and bone marrow fluid were collected from a steroid treatment group and a control group during hip replacement surgery, and an enzyme-linked immunosorbent assay (ELISA) was used to measure the adiponectin, leptin, and PAI-1 levels. Adiponectin and leptin showed no significant differences between bone marrow and blood levels, but PAI-1 was significantly higher in bone marrow. The steroid treatment group had higher levels of leptin and PAI-1 in both the blood and bone marrow than the control group. PAI-1 was present at high concentrations in the bone marrow and increased by steroid treatment. High levels of PAI-1 in bone marrow may influence intraosseous hemodynamics and may induce necrotic bone disorders. PMID- 27356610 TI - Novel Innate Immune Genes Regulating the Macrophage Response to Gram Positive Bacteria. AB - Host variation in Toll-like receptors and other innate immune signaling molecules alters infection susceptibility. However, only a portion of the variability observed in the innate immune response is accounted for by known genes in these pathways. Thus, the identification of additional genes that regulate the response to Gram positive bacteria is warranted. Bone marrow-derived macrophages (BMMs) from 43 inbred mouse strains were stimulated with lipotechoic acid (LTA), a major component of the Gram positive bacterial cell wall. Concentrations of the proinflammatory cytokines IL-6, IL-12, and TNF-alpha were measured. In silico whole genome association (WGA) mapping was performed using cytokine responses followed by network analysis to prioritize candidate genes. To determine which candidate genes could be responsible for regulating the LTA response, candidate genes were inhibited using RNA interference (RNAi) and were overexpressed in RAW264.7 macrophages. BMMs from Bdkrb1-deficient mice were used to assess the effect of Bdkrb1 gene deletion on the response to LTA, heat-killed Streptococcus pneumoniae, and heat-killed Staphylococcus aureus WGA mapping identified 117 loci: IL-6 analysis yielded 20 loci (average locus size = 0.133 Mb; 18 genes), IL 12 analysis produced 5 loci (0.201 Mb average; 7 genes), and TNF-alpha analysis yielded 92 loci (0.464 Mb average; 186 genes of which 46 were prioritized by network analysis). The follow-up small interfering RNA screen of 71 target genes identified four genes (Bdkrb1, Blnk, Fbxo17, and Nkx6-1) whose inhibition resulted in significantly reduced cytokine production following LTA stimulation. Overexpression of these four genes resulted in significantly increased cytokine production in response to LTA. Bdkrb1-deficient macrophages were less responsive to LTA and heat-killed S. aureus, validating the genetic and RNAi approach to identify novel regulators of the response to LTA. We have identified four innate immune response genes that may contribute to Gram positive bacterial susceptibility. PMID- 27356611 TI - Untangling the Contributions of Sex-Specific Gene Regulation and X-Chromosome Dosage to Sex-Biased Gene Expression in Caenorhabditis elegans. AB - Dosage compensation mechanisms equalize the level of X chromosome expression between sexes. Yet the X chromosome is often enriched for genes exhibiting sex biased, i.e., imbalanced expression. The relationship between X chromosome dosage compensation and sex-biased gene expression remains largely unexplored. Most studies determine sex-biased gene expression without distinguishing between contributions from X chromosome copy number (dose) and the animal's sex. Here, we uncoupled X chromosome dose from sex-specific gene regulation in Caenorhabditis elegans to determine the effect of each on X expression. In early embryogenesis, when dosage compensation is not yet fully active, X chromosome dose drives the hermaphrodite-biased expression of many X-linked genes, including several genes that were shown to be responsible for hermaphrodite fate. A similar effect is seen in the C. elegans germline, where X chromosome dose contributes to higher hermaphrodite X expression, suggesting that lack of dosage compensation in the germline may have a role in supporting higher expression of X chromosomal genes with female-biased functions in the gonad. In the soma, dosage compensation effectively balances X expression between the sexes. As a result, somatic sex biased expression is almost entirely due to sex-specific gene regulation. These results suggest that lack of dosage compensation in different tissues and developmental stages allow X chromosome copy number to contribute to sex-biased gene expression and function. PMID- 27356612 TI - A Genealogical Look at Shared Ancestry on the X Chromosome. AB - Close relatives can share large segments of their genome identical by descent (IBD) that can be identified in genome-wide polymorphism data sets. There are a range of methods to use these IBD segments to identify relatives and estimate their relationship. These methods have focused on sharing on the autosomes, as they provide a rich source of information about genealogical relationships. We hope to learn additional information about recent ancestry through shared IBD segments on the X chromosome, but currently lack the theoretical framework to use this information fully. Here, we fill this gap by developing probability distributions for the number and length of X chromosome segments shared IBD between an individual and an ancestor k generations back, as well as between half and full-cousin relationships. Due to the inheritance pattern of the X and the fact that X homologous recombination occurs only in females (outside of the pseudoautosomal regions), the number of females along a genealogical lineage is a key quantity for understanding the number and length of the IBD segments shared among relatives. When inferring relationships among individuals, the number of female ancestors along a genealogical lineage will often be unknown. Therefore, our IBD segment length and number distributions marginalize over this unknown number of recombinational meioses through a distribution of recombinational meioses we derive. By using Bayes' theorem to invert these distributions, we can estimate the number of female ancestors between two relatives, giving us details about the genealogical relations between individuals not possible with autosomal data alone. PMID- 27356613 TI - A Genomic Resource for the Development, Improvement, and Exploitation of Sorghum for Bioenergy. AB - With high productivity and stress tolerance, numerous grass genera of the Andropogoneae have emerged as candidates for bioenergy production. To optimize these candidates, research examining the genetic architecture of yield, carbon partitioning, and composition is required to advance breeding objectives. Significant progress has been made developing genetic and genomic resources for Andropogoneae, and advances in comparative and computational genomics have enabled research examining the genetic basis of photosynthesis, carbon partitioning, composition, and sink strength. To provide a pivotal resource aimed at developing a comparative understanding of key bioenergy traits in the Andropogoneae, we have established and characterized an association panel of 390 racially, geographically, and phenotypically diverse Sorghum bicolor accessions with 232,303 genetic markers. Sorghum bicolor was selected because of its genomic simplicity, phenotypic diversity, significant genomic tools, and its agricultural productivity and resilience. We have demonstrated the value of sorghum as a functional model for candidate gene discovery for bioenergy Andropogoneae by performing genome-wide association analysis for two contrasting phenotypes representing key components of structural and non-structural carbohydrates. We identified potential genes, including a cellulase enzyme and a vacuolar transporter, associated with increased non-structural carbohydrates that could lead to bioenergy sorghum improvement. Although our analysis identified genes with potentially clear functions, other candidates did not have assigned functions, suggesting novel molecular mechanisms for carbon partitioning traits. These results, combined with our characterization of phenotypic and genetic diversity and the public accessibility of each accession and genomic data, demonstrate the value of this resource and provide a foundation for future improvement of sorghum and related grasses for bioenergy production. PMID- 27356614 TI - Apparent Epigenetic Meiotic Double-Strand-Break Disparity in Saccharomyces cerevisiae: A Meta-Analysis. AB - Previously published, and some unpublished, tetrad data from budding yeast (Saccharomyces cerevisiae) are analyzed for disparity in gene conversion, in which one allele is more often favored than the other (conversion disparity). One such disparity, characteristic of a bias in the frequencies of meiotic double strand DNA breaks at the hotspot near the His4 locus, is found in diploids that undergo meiosis soon after their formation, but not in diploids that have been cloned and frozen. Altered meiotic DNA breakability associated with altered metabolism-related chromatin states has been previously reported. However, the above observations imply that such differing parental chromatin states can persist through at least one chromosome replication, and probably more, in a common environment. This conclusion may have implications for interpreting changes in allele frequencies in populations. PMID- 27356616 TI - Synthesis and photophysical properties of Ir(iii)/Re(i) dyads: control of Ir->Re photoinduced energy transfer. AB - A series of dinuclear Ir(iii)/Re(i) complexes has been prepared based on a family of symmetrical bridging ligands containing two bidentate N,N'-chelating pyrazolyl pyridine termini, connected by a central aromatic or aliphatic spacer. The Ir(iii) termini are based on {Ir(F2ppy)2}(+) units (where F2ppy is the cyclometallating anion of a fluorinated phenylpyridine) and the Re(i) termini are based on {Re(CO)3Cl} units. Both types of terminus are luminescent, with the Ir based unit showing characteristic strong, structured phosphorescence in the blue region (maximum 452 nm) with a triplet excited state energy of 22 200 cm(-1) and the Re-based unit showing much weaker and lower-energy phosphorescence (maximum 530 nm) with a triplet excited state energy of 21 300 cm(-1). The energy gradient between the two excited states allows for partial Ir->Re photoinduced energy transfer, with substantial (but incomplete) quenching of the higher-energy Ir based emission component and sensitised emission - evidenced by an obvious grow in component - on the lower-energy Re-based emission. The Ir->Re energy-transfer rate constants vary over the range 1-8 * 10(7) s(-1) depending on the bridging ligand: there is no simple correlation between bridging ligand structure and energy-transfer rate, possibly because this will depend substantially on the conformation of these flexible molecules in solution. To test the role of ligand conformation further, we investigated a complex in which the bridging chain is a (CH2CH2O)6 unit whose conformation is known to be solvent-polarity dependent, with such chains adopting an open, elongated conformation in water and more compact, folded conformations in organic solvents. There was a clear link between the rate and extent of Ir->Re energy-transfer which reduced in polar solvents as the chain became elongated and the Ir/Re separation was larger; and increased in less polar solvents as the chain adopted a more compact conformation and the Ir/Re separation was reduced. PMID- 27356617 TI - Mechanism of Co-C photodissociation in adenosylcobalamin. AB - A mechanism of Co-C bond photodissociation in the base-on form of adenosylcobalamin (AdoCbl) was investigated by time-dependent density functional theory (TD-DFT). The key mechanistic step involves singlet radical pair (RP) generation from the first electronically excited state (S1). To connect TD-DFT calculations with ultra-fast excited state dynamics, the potential energy surface (PES) of the S1 state was constructed using Co-C and Co-NIm axial coordinates. The S1 PES can be characterized by two minima separated by a seam resulting from the crossing of two surfaces, of metal-to-ligand charge transfer (MLCT) character near the minimum, and a shallow ligand field (LF) surface at elongated axial bond distances. Only one possible pathway for photolysis (path A) was identified based on energetic grounds. This pathway is characterized by the first elongation of the Co-C bond, followed by photolysis from an LF state where the axial base is partially detached. A new perspective on the photolysis of AdoCbl is then gained by connecting TD-DFT results with available experimental observations. PMID- 27356618 TI - A dinuclear ruthenium(II) complex as turn-on luminescent probe for hypochlorous acid and its application for in vivo imaging. AB - A dinuclear ruthenium(II) complex Ruazo was designed and synthesized, in which oxidative cyclization of the azo and o-amino group was employed for the detection of hypochlorous acid (HClO) in aqueous solution. The non-emissive Ruazo formed highly luminescent triazole-ruthenium(II) complex in presence of HClO and successfully imaged HClO in living cell and living mouse. PMID- 27356619 TI - Four-junction superconducting circuit. AB - We develop a theory for the quantum circuit consisting of a superconducting loop interrupted by four Josephson junctions and pierced by a magnetic flux (either static or time-dependent). In addition to the similarity with the typical three junction flux qubit in the double-well regime, we demonstrate the difference of the four-junction circuit from its three-junction analogue, including its advantages over the latter. Moreover, the four-junction circuit in the single well regime is also investigated. Our theory provides a tool to explore the physical properties of this four-junction superconducting circuit. PMID- 27356621 TI - FRESH AIR: an implementation research project funded through Horizon 2020 exploring the prevention, diagnosis and treatment of chronic respiratory diseases in low-resource settings. AB - This protocol describes FRESH AIR, an implementation science project exploring how to improve the prevention, diagnosis and treatment of chronic lung diseases in contexts with limited healthcare resources. It consists of inter-related studies that take place in four countries that are part of the International Primary Care Respiratory Group's (IPCRG) global network: Uganda, the Kyrgyz Republic, Vietnam and Greece. The project has been funded by the European Commission Horizon 2020 research programme and runs from October 2015 until September 2018. PMID- 27356620 TI - Prosaposin is a regulator of progranulin levels and oligomerization. AB - Progranulin (GRN) loss-of-function mutations leading to progranulin protein (PGRN) haploinsufficiency are prevalent genetic causes of frontotemporal dementia. Reports also indicated PGRN-mediated neuroprotection in models of Alzheimer's and Parkinson's disease; thus, increasing PGRN levels is a promising therapeutic for multiple disorders. To uncover novel PGRN regulators, we linked whole-genome sequence data from 920 individuals with plasma PGRN levels and identified the prosaposin (PSAP) locus as a new locus significantly associated with plasma PGRN levels. Here we show that both PSAP reduction and overexpression lead to significantly elevated extracellular PGRN levels. Intriguingly, PSAP knockdown increases PGRN monomers, whereas PSAP overexpression increases PGRN oligomers, partly through a protein-protein interaction. PSAP-induced changes in PGRN levels and oligomerization replicate in human-derived fibroblasts obtained from a GRN mutation carrier, further supporting PSAP as a potential PGRN-related therapeutic target. Future studies should focus on addressing the relevance and cellular mechanism by which PGRN oligomeric species provide neuroprotection. PMID- 27356622 TI - Humoral response against host-mimetic homologous epitopes of Mycobacterium avium subsp. paratuberculosis in Japanese multiple sclerosis patients. AB - Several works have demonstrated the existence of a link between Mycobacterium avium subsp. paratuberculosis (MAP) and MS in Italy. In this study, we analyzed the serology of MAP in a Japanese population while looking at several markers of MAP. Fifty MS patients, 12 clinically isolated syndrome (CIS) patients, 30 other neurological disorders (OND) patients, and 50 healthy controls (HCs) were tested using ELISA for the presence of IgG antibodies toward immunodominant epitopes MAP_0106c121-132, homologues MBP85-98, homologues IRF5424-432, MAP_402718-32, and MAP_2694295-303. MAP-positive patients were also analyzed in relation to their clinical/demographic characteristics. Amongst all peptides, only antibodies against MAP_2694295-303 were more prevalent in MS patients (30%), as compared to OND patients (3%) (p = 0.009; area under roc curve (AUC) = 0.61) and HCs (2%) (p = 0.0004; AUC = 0.65) and in CIS patients (25%) compared to HCs (p = 0.023; AUC = 0.55). Logistic regression analysis showed a higher frequency of anti-MAP_2694295 303 antibodies in the sera of oligoclonal bands positive MS patients (p = 0.2; OR = 2, 95%CI: 0.55-7.7). These findings support the view that MAP could act as a risk factor or a triggering agent of MS in some Japanese patients with a genetic susceptibility to the mycobacterium. PMID- 27356623 TI - Growing Ultra-flat Organic Films on Graphene with a Face-on Stacking via Moderate Molecule-Substrate Interaction. AB - The electronic properties of small molecule organic crystals depend heavily on the molecular orientation. For multi-layer organic photovoltaics, it is desirable for the molecules to have a face-on orientation in order to enhance the out-of plane transport properties. However, it is challenging to grow well-ordered and smooth films with a face-on stacking on conventional substrates such as metals and oxides. In this work, metal-phthalocyanine molecules is used as a model system to demonstrate that two-dimensional crystals such as graphene can serve as a template for growing high quality, ultra-flat organic films with a face-on orientation. Furthermore, the molecule-substrate interaction is varied systematically from strong to weak interaction regime with the interaction strength characterized by ultrafast electron transfer measurements. We find that in order to achieve the optimum orientation and morphology, the molecule substrate interaction needs to be strong enough to ensure a face-on stacking while it needs to be weak enough to avoid film roughening. PMID- 27356624 TI - Ablation of MCL1 expression by virally induced microRNA-29 reverses chemoresistance in human osteosarcomas. AB - Osteosarcoma is a rare disease diagnosed as malignant bone tumor. It is generally refractory to chemotherapy, which contributes to its poor prognosis. The reversal of chemoresistance is a major clinical challenge to improve the prognostic outcome of osteosarcoma patients. We developed a tumor-specific replication competent oncolytic adenovirus, OBP-301 (telomelysin) and assessed its synergistic effects with chemotherapeutic agents (cisplatin and doxorubicin) using human osteosarcoma cell lines and a xenograft tumor model. The molecular mechanism underlying the chemosensitizing effect of OBP-301 was evaluated in aspects of apoptosis induction. OBP-301 inhibits anti-apoptotic myeloid cell leukemia 1 (MCL1) expression, which in turn leads to chemosensitization in human osteosarcoma cells. The siRNA-mediated knockdown of MCL1 expression sensitized human osteosarcoma cells to common chemotherapeutic agents. We also found that upregulation of microRNA-29 targeting MCL1 via virally induced transcriptional factor E2F-1 activation was critical for the enhancement of chemotherapy-induced apoptosis in osteosarcoma cells. Telomerase-specific oncolytic adenovirus synergistically suppressed the viability of human osteosarcoma cells in combination with chemotherapeutic agents. The combination treatment also significantly inhibited tumor growth, as compared to monotherapy, in an osteosarcoma xenograft tumor model. Our data suggest that replicative virus mediated tumor-specific MCL1 ablation may be a promising strategy to attenuate chemoresistance in osteosarcoma patients. PMID- 27356626 TI - Modelling gastrointestinal parasitism infection in a sheep flock over two reproductive seasons: in silico exploration and sensitivity analysis. AB - In reproducing ewes, a periparturient breakdown of immunity is often observed to result in increased fecal egg excretion, making them the main source of infection for their immunologically naive lambs. In this study, we expanded a simulation model previously developed for growing lambs to explore the impact of the genotype (performance and resistance traits) and host nutrition on the performance and parasitism of both growing lambs and reproducing ewes naturally infected with Teladorsagia circumcincta. Our model accounted for nutrient demanding phases, such as gestation and lactation, and included a supplementary module to manage the age structure of the ewe flock. The model was validated by comparison with published data. Because model parameters were unknown or poorly estimated, detailed sensitivity analysis of the model was performed for the sheep mortality and the level of infection, following a preliminary screening step. The parameters with the greatest effect on parasite-related outputs were those driving animal growth and milk yield. Our model enables different parasite control strategies (host nutrition, breeding for resistance and anthelmintic treatments) to be assessed on the long term in a sheep flock. To optimize in silico exploration, the parameters highlighted by the sensitivity analysis should be refined with real data. PMID- 27356625 TI - Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis. AB - Gout is a form of crystal arthropathy where monosodium urate (MSU) crystals deposit and elicit inflammation in a joint. Diagnosis of gout relies on identification of MSU crystals under a compensated polarized light microscope (CPLM) in synovial fluid aspirated from the patient's joint. The detection of MSU crystals by optical microscopy is enhanced by their birefringent properties. However, CPLM partially suffers from the high-cost and bulkiness of conventional lens-based microscopy, and its relatively small field-of-view (FOV) limits the efficiency and accuracy of gout diagnosis. Here we present a lens-free polarized microscope which adopts a novel differential and angle-mismatched polarizing optical design achieving wide-field and high-resolution holographic imaging of birefringent objects with a color contrast similar to that of a standard CPLM. The performance of this computational polarization microscope is validated by imaging MSU crystals made from a gout patient's tophus and steroid crystals used as negative control. This lens-free polarized microscope, with its wide FOV (>20 mm(2)), cost-effectiveness and field-portability, can significantly improve the efficiency and accuracy of gout diagnosis, reduce costs, and can be deployed even at the point-of-care and in resource-limited clinical settings. PMID- 27356627 TI - Synthesis and Antioxidant Properties of Novel Memantine Derivatives. AB - BACKGROUND: Medicinal chemistry methodologies are presently used to develop multifunctional molecules which simultaneously reduce oxidative stress, excitotoxicity, metal dyshomeostasis, and neuroinflammation that characterize neuropathological conditions, such as Alzheimer's Disease. RESULTS: Memantine (MEM) derivatives 1-6 were designed and synthesized as novel multifunctional entities with antioxidant and neuroprotective capabilities to manage neurodegenerative diseases, such as Alzheimer's Disease. In vitro neuroprotective studies were performed by using astroglial GL15 cell line to assess antioxidant capability of MEM derivatives 1-6. CONCLUSION: Our outcomes showed that compounds 1 and 5 (at the concentration of 10 MUM), containing as antioxidant portion residues of N-acetyl-Cys-OH and N-acetyl-Cys(Allyl)-OH, respectively, revealed a significant neuroprotective activity against oxidative stress, as assessed by NBT assays. PMID- 27356629 TI - A Teenager With Sulfasalazine-Associated DRESS Syndrome After the Introduction of Amoxicillin. PMID- 27356628 TI - MicroRNA-335 inhibits bladder cancer cell growth and migration by targeting mitogen-activated protein kinase 1. AB - The abnormal expression of microRNAs (miRs) as oncogenes or tumor-suppressor genes has been widely investigated in various tumor types. However, the roles of miR-335 in bladder cancer cells have remained elusive. The aim of the present study was to assess the expression of miR-335 in bladder cancer as well as the effects of miR-335 on bladder cancer cell proliferation, metastasis and apoptosis. PCR and western blot analyses revealed that miR-335 was significantly downregulated in bladder cancer tissues, and low levels of miR-335 were associated with more aggressive phenotypes of bladder cancer. Overexpression of miR-335 in T24 cells inhibited cell proliferation and induced apoptosis as indicated by an MTT assay and flow cytometric analysis, respectively. Furthermore, overexpression of miR-335 significantly suppressed cell migration, as indicated by a Transwell assay. The expression of mitogen-activated protein kinase (MAPK)1 was decreased after overexpression of miR-335, indicating that MAPK1 may be a target gene of miR-335. In addition, silencing of MAPK1 inhibited the proliferation and migration of bladder cancer cells. In conclusion, the results of the present study demonstrated that miR-335 was significantly downregulated in bladder cancer, and may act as a tumor suppressor through repression of MAPK1. PMID- 27356630 TI - Managing a "New" Murmur in Healthy Children and Teens. AB - An asymptomatic child with a murmur can be challenging practice management conundrum. Some providers refer all patients with a "new" murmur to a cardiologist, likely resulting in excessive resource utilization and parental anxiety. This study examines whether the prevalence of significant cardiac pathology differs in asymptomatic patients aged 2 to 18 years who were referred for a murmur that was "new" versus those referred for a murmur that was known to exist and followed conservatively during the previous 2 years. Of 473 patients meeting inclusion criteria, 33/473 (7.0%) were diagnosed with cardiac pathology, with 21/357 (5.9%) occurring among "new" murmur referrals and 12/116 (10.3%) occurring among "known" murmur referrals. Notably, 34/357 (9.5%) patients referred for a "new" murmur had no murmur present when assessed by the cardiologist. This study suggests that asymptomatic children with a "new" murmur may be conservatively managed. This may lessen health care resource utilization rates and overall parental anxiety. PMID- 27356631 TI - The Determination of Procalcitonin Concentration in Early-Onset Neonatal Infection. AB - The aim of this study was to assess the clinical usefulness of blood procalcitonin (PCT) levels for the diagnosis and therapeutic monitoring of early onset neonatal sepsis (EONS). PCT as well as C-reactive protein (CRP) levels and white blood cell (WBC) count were measured in venous blood from 57 infected and 72 uninfected neonates. Differences between groups for PCT, CRP, and WBC levels were significant. The threshold value on the receiver operating characteristic curve in the prediction of EONS was 5.33 ng/mL for PCT, 9.3 mg/L for CRP, and 14.9 * 109/L for WBC. There was no effect of antibiotic administered to the mother on PCT, CRP, and WBC levels in neonatal blood sampled before treatment of EONS. Evidently reduced PCT levels are observed after 2 days of treatment. The authors conclude that prenatal antibiotic therapy does not reduce the value of PCT levels in blood for the diagnosis of EONS. PMID- 27356633 TI - Acute Myocarditis With Very High Troponin but No Ventricular Dysfunction. PMID- 27356632 TI - Cerebral Magnetic Resonance Imaging in Children With Prenatal Drug Exposure. AB - This study aimed to evaluate cerebral magnetic resonance imaging (MRI) scans of children with prenatal drug exposure in a clinical context. A hospital-based cohort of 10- to 14-year-old children, prenatally exposed to alcohol, opioids, and polysubstances, and a group of sex- and age-matched controls were examined with cerebral MRI. Scans obtained from 34 exposed children and 40 controls were scored based on the presence and degree of pathology by an experienced pediatric neuroradiologist blinded to the participants' background. Overall visual detectable MRI pathology was found in 35% of the exposed children and 33% of the controls (odds ratio = 1.08; 95% confidence interval = 0.36-3.25). No specific imaging pattern following prenatal drug exposure was seen by the means of simple visual analysis of cerebral MRI scans. Although cerebral MRI is feasible, it is probably of limited value in the clinical assessment of children with prenatal drug exposure. PMID- 27356634 TI - One-Month-Old Infant With Hypotonia and Cardiorespiratory Arrest. PMID- 27356636 TI - [Holistic Integral medicine towards a new era of medical advances]. PMID- 27356635 TI - miR-200b inhibits migration and invasion in non-small cell lung cancer cells via targeting FSCN1. AB - Distant metastasis of non-small cell lung cancer (NSCLC) leads to high postoperative recurrence and low long-term survival rates. Deregulation of microRNA (miR)-200b has been demonstrated to be associated with NSCLC metastasis. However, the underlying molecular mechanism of miR-200b in mediating NSCLC cell migration and invasion remains to be fully elucidated. In the current study, reverse transcription-quantitative polymerase chain reaction data indicated that miR-200b was significantly downregulated in several NSCLC cell lines, including A549, L78, H1229, H358 and H1650, compared with a normal human lung epithelial cell line, BEAS-2B. Overexpression of miR-200b significantly inhibited NSCLC cell migration and invasion. Bioinformatics analysis and a luciferase reporter assay were additionally conducted, which identified fascin actin-bundling protein 1 (FSCN1) as a novel target of miR-200b. In addition, miR-200b negatively mediated the protein expression of FSCN1 in NSCLC H1229 cells. siRNA-mediated FSCN1 inhibition also significantly inhibited the migration and invasion of H1229 cells. In addition, overexpression of FSCN1 effectively reversed the suppressive effect of miR-200b overexpression on NSCLC cell migration and invasion. Accordingly, it is suggested that miR-200b is able to inhibit the migration and invasion of NSCLC cells, partly at least, via targeting FSCN1. The current study provides novel insight into miR-200 regulation in NSCLC metastasis. PMID- 27356637 TI - [Target cells of cytotoxic T cells in severe aplastic anemia in vitro]. AB - OBJECTIVE: To clarify the specific target of severe aplastic anemia (SAA) immune attack via identifying the target cells of cytotoxic T cell attacks and the expression of apoptosis ligand on each department and each stage of bone marrow hematopoietic cells. METHODS: A total of 15 SAA patients and 15 normal controls were recruited in the Department of Hematology, Tianjin Medical University General Hospital between March 2011 and March 2012. Factor associated suicide(Fas) protein expression of CD34(+) , CD14(+) , CD33(+) , and GlycoA(+) cells in bone marrow was detected by flow cytometry. The CD8(+) T cells of SAA patients and CD3(-) bone marrow mononuclear cells (BMMNC) of controls were sorted by immunomagnetic separation and co-cultured for 72 hours. The apoptosis rate of CD34(+) , CD14(+) , CD33(+) , and GlycoA(+) cells were measured with flow cytometry. RESULTS: The expression of Fas protein in CD34(+) cells in SAA patients (46.59%+/- 27.60%) was significantly higher than that in control group (8.89%+/-7.28%, P<0.01). The expressions of Fas protein in CD14(+) , CD33(+) and GlycoA(+) cells in SAA group(29.29%+/-9.23%, 46.88%+/-14.30%, 15.15%+/-9.26%) were lower than those in control group(51.25%+/-38.36%, 72.06%+/-39.88%, 50.38%+/ 39.88%, all P<0.05). The apoptosis rates of CD34(+) , CD33(+) and CD14(+) cells in the experimental group (CD8(+) T cells of SAA patients co-cultured with CD3(-) BMMNC of controls: 55.43%+/-20.50%, 38.13%+/-20.10%, 61.87%+/-21.65%)were significantly higher than those of the control group (CD8(+) T cells of controls co-cultured with CD3(-) BMMNC of controls: 35.02%+/-13.95%, 23.44%+/-10.33%, 37.04%+/-22.41%, all P<0.05). CONCLUSIONS: Cytotoxic T cells in SAA patients may have a killing effect on hematopoietic stem/progenitor cells, and granulocytic and macrophagocytic cells from normal bone marrow. Moreover, Fas/Fas ligand mediated apoptosis may play an important role in the immune pathogenesis of SAA. CD34(+) cells show markedly increased Fas protein expression, which may be the main target cells in the process of immune injury in SAA patients. PMID- 27356638 TI - [Clinicopathological characteristics and prognosis of different molecular types of breast cancer]. AB - OBJECTIVE: To investigate the clinicopathological characteristics of 4 subtypes of breast cancer, Luminal A, Luminal B, human epidermal growth factor receptor 2(HER2), triple-negative and their associated prognostic factors. METHODS: The clinical characteristics and prognosis of 102 patients with breast cancer who treated in Wuhan University Renmin Hospital from January 2011 to November 2012 were retrospectively analyzed. RESULTS: The proportion of each subtype was Luminal A 27.5%, Luminal B 35.3%, HER2 14.7%, and triple-negative 22.5%. The age range was from 22 to 75 years old, with median age of 48.0 years old. All patients underwent surgery and 98 cases were also treated with chemotherapy/endocrine+ Herceptin therapy (96.1%)after surgery. The tumor size, histological grade, and lymph node metastasis had significant difference in different subtypes of breast cancer (P<0.05). Further analysis showed the proportion of HER2 tumor<=2 cm (4, 26.7%)had a tendency of smaller than that in luminal A(20, 71.4%) or triple negative(16, 69.6%) (P=0.009>0.008, P=0.019>0.008). Histological III grade proportion in patients with HER2 subtype (8, 53.3%) was in greater tendency than that with Luminal A subtype(23, 82.1%) (P=0.039>0.008). The proportion of patients with no metastatic lymph nodes in triple negative subtype(7, 30.4%) had a tendency of smaller than that in HER2 subtype(7, 46.7%) or Luminal B subtype(17, 47.2%)(P=0.019>0.008, P=0.016>0.008). There were no significant differences in age of onset, menstruation status, operation, family cancer history, and the risk of recurrence and metastasis in different subtypes (P>0.05). In Luminal A subtype, three-years overall survival rate was 100%, and one-, two-, three-year event-free survival rate were all 92.9%. In Luminal B subtype, three-year overall survival rate was 100%, event free survival rate at one-, two- and three-year were all 97.2%. In HER2 subtype, three-year overall survival rate was 100%, one-, two- and three-year event-free survival rate were 100%, 100%, and 93.3%, respectively. The 1, 2, 3 years overall survival rate of triple-negative subtype were 100%, 95.7%, and 95.7%, respectively. One-, two- and three-year event-free survival rate of triple negative subtype were 95.7%, 91.3%, and 90.0% respectively. Whether triple negative subtype, recurrence risk, age of onset, menstrual status, tumor size, histological grade, lymph node metastasis, surgery, breast cancer or other family history of cancer were not significantly related with three-year event-free survival rate (P>0.05). CONCLUSIONS: Luminal subtype had the largest proportion and better prognosis. The proportion of tumor >2 cm and histological grade III in patients with HER2 subtype was larger, and three-year event-free survival rate of this patients was lower. Triple-negative subtype had a greater tendency of lymph node metastasis and the lowest three-year event-free survival. Tumor size, histological grade and lymph node metastasis may be the important factors for the prognosis of breast cancer. PMID- 27356639 TI - [Diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration in stage I and stage II of sarcoidosis]. AB - OBJECTIVE: To evaluate the diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in stage I and stage II of sarcoidosis. METHODS: There were 55 patients of sarcoidosis selected from January 2012 to October 2014 in the First Affiliated Hospital of Soochow University. The diagnostic positive rate and the positive rate in stage I and II patients with sarcoidosis through EBUS-TBNA, conventional transbronchial needle aspiration (cTBNA), endobronchial biopsy (EBB) combined with transbronchial lung biopsy (TBLB) were calculated. The positive rate of single lymph node puncture and the positive rate of different size of lymph node were compared. The difference of the positive rate of lymph nodes in different stations was checked. By calculating the diagnostic yield of EBUS-TBNA in sarcoidosis patients, the practicality and safety of EBUS-TBNA in diagnosing stage I or stage II sarcoidosis was assessed. RESULTS: Among 55 patients, 46 patients obtained positive results through EBUS-TBNA or cTBNA. There were 18 patients who had only received EBUS-TBNA among a total of 55 patients diagnosed with sarcoidosis, positive results appeared in 17 cases, while cTBNA was 9/15. There were 20 cases diagnosed in which both had EBUS-TBNA and cTBNA. The diagnostic rate of cTBNA combined with EBB and TBLB was 25/26, while combined with EBUS-TBNA was 21/21. Totally 90 lymph nodes were punctured by EBUS-TBNA, in which 65 lymph nodes got the positive results (65/90) while 49 lymph nodes got the positive results by TBNA in 93 punctured lymph nodes (49/93). The diagnostic positive rate in the lymph nodes with a short diameter >=2 cm was 33/37 by EBUS-TBNA, while it was 12/19 in those whose short diameter 1-<2 cm. By cTBNA, the diagnostic positive rate was 15/26 and 11/28. No serious adverse events occurred. CONCLUSIONS: The diagnosis of sarcoidosis in stage I and stage II by EBUS-TBNA is safe and effective, while choosing the most noticeable swelling lymph node to puncture is recommended. Combining the EBUS-TBNA with traditional bronchoscope technology can obtain a further higher diagnostic efficiency. PMID- 27356640 TI - [The application of Hoffmann method in the establishment of children's reference intervals of erythrocyte count]. AB - OBJECTIVE: To verify the reliability and feasibility of Hoffmann method in establishing pediatric reference intervals (RI) of erythrocyte count. METHODS: Three hundreds and ninty-two thousands of hospital-based data for erythrocyte count of children aged in 1 to 17, measured by the Sysmex Xs-800i, was collected from Beijing Children's Hospital during January to December 2014. Outliers were removed using the Dixon method, then Hoffmann method was conducted to establish the gender and age stratified pediatric RIs of erythrocyte count. The erythrocyte count of 2 217 healthy children, recruited from Beijing Children's Hospital and Liaocheng Children's Hospital in Shandong province, was conducted as normal reference to verify the reliability of Hoffmann method in establishing RIs and to compare with existing RIs. RESULTS: In 4 subgroups as following, male aging 1 to 12 years, male aging 13 to 17 years, female aging 1 to 12 years, female aging 13 to 17 years, the RIs of erythrocyte count established using Hoffmann method were (4.1-5.4)*10(12)/L, (4.4-5.7)*10(12)/L, (4.0-5.3)*10(12)/L, (4.0-5.3)*10(12)/L, respectively. The verification results in 2 217 healthy children showed that the proportions of out of range in four subgroups were 6.17%, 8.81%, 6.22%, 7.78%, respectively. CONCLUSION: Hoffmann method produce reliable RIs according with the actual situation in healthy children, which is also convenient and is worth popularizing in clinical practice. PMID- 27356641 TI - [The application of the three-step approach based on the regional distribution of hepatic vessel in laparoscopic hemihepatectomy]. AB - OBJECTIVE: To investigate the clinical significance of the three-step approach in laparoscopic hemihepatectomy. METHODS: A total of 32 patients received laparoscopic hemihepatectomy with the three-step approach in Yijishan Hospital affiliated to Wannan Medical College between Aug 2013 and Oct 2015. All patients underwent thin slice CT scan and hemihepatectomy was imitated with the imagic explorer, preoperatively. The vessel distribution was observed at the section and the three-step approach was used in the hemihepatectomy. Pre- and post-operative data were collected and analyzed retrospectively. RESULTS: The length of middle hepatic vein (MHV) was (59.1+/-12.9) mm and the number of branchs to the left and right lobe were 3.07+/-0.78 and 3.11+/-0.64 respectively. The distance between the first branch of MHV and the diaphragmatic surface was (28.07+/-3.74) mm and the distance between MHV and the visceral surface was (14.4+/-4.3) mm. The laparoscopic surgeries (left hemihepatectomy in 28 and right hemihepatectomy in 4) were performed successfully in all cases with the three-step approach, without any conversion to the open surgeries. The operation time was (165+/-42) min in left hemihepatectomy and (305+/-50) min in right hemihepatectomy. The intraoperative blood loss was (242+/-65) ml in left hemihepatectomy and (695+/ 122)ml in right hemihepatectomy. All the patients recovered well without severe complications except for bile leakage in 3 patients who were cured with drainage. The postoperative hospital stay was (7.96+/-1.8) d. CONCLUSIONS: the distribution of vessel is regional at the section of hemihepatectomy and the three-step approach based on this feature is safe and effective in laparoscopic hemihepatectomy, which can shorten the operation time and reduce the difficulty of operation. PMID- 27356642 TI - [A clinical study of the efficacy of automated intermittent boluses for continuous fascia iliaca block]. AB - OBJECTIVE: To compare two different regimens of continuous ultrasound-guided fascia iliaca compartment block (FICB) for postoperative analgesia after total hip arthroplasty (THA). METHODS: Approved by the Peking University Third Hospital ethics committee, sixty patients undergoing selective single total hip replacement in Peking University Third Hospital from May.2015 to Mar.2016 were included. Before neuraxial block, continuous ultrasound-guided FICB were administered. Patients were randomly divided into the continuous infusion group(n=30) and the automated intermittent boluses group(n=30). 10 ml/h of 0.2% ropivacaine was continuously infused for 48 hours in the continuous infusion group. 10 ml of 0.2% ropivacaine was automated injected every 60 mins in the automated intermittent boluses group. Numerical Rating Pain Scale(NRPS)was used to assess pain intensity at 4, 8, 12, 24, 36, 48 h after block at rest and during functional exercise. The usage of pethidine postoperatively, the incidence of opioid related adverse effect and patient satisfaction scores at 48 h were also recorded. RESULTS: The pain score at rest 8, 12, 24, 36 h of the automated intermittent boluses group were 2 (1-3), 2 (1-3), 2 (1-3), 2 (1-3) score, which were lower than the continuous infusion group: 4 (2-6), 3 (2-5), 4 (3-5), 2 (1-4) score, the differences were statistically significant (Z=-6.493, -6.267, -6.235, 3.244, all P<0.05). The pain score during active and passive functional exercise at 8, 12, 24, 36 h of the automated intermittent boluses group were 4 (3-5), 4 (3 5), 2 (1-3), 1(0-3) score, which were lower than the continuous infusion group: 6 (4-7), 5 (4-7), 4 (2-6), 4 (2-5) score, the differences were statistically significant (Z=-6.499, -6.499, -5.081, -6.667, all P<0.05). The usage of pethidine postoperatively and the incidence of opioid related adverse effect of the automated intermittent boluses group were 10.0% and 3.3%, which were lower than the continuous infusion group: 33.3% and 26.7% , the differences were statistically significant (chi(2)=5.057, 4.500, all P<0.05). Patient satisfaction score at 48 h of the automated intermittent boluses group was (8.3+/-0.7)score, which was higher than the continuous infusion group: (7.4+/-0.7)score, the difference was statistically significant (t=-5.632, P<0.05). CONCLUSIONS: Both regimens can provide effective analgesia after total hip arthroplasty. Compared with the continuous infusion group, the automated intermittent boluses group for continuous fascia iliaca block can provide better analgesic effect , with less remedial analgesia. PMID- 27356643 TI - [Clinical analysis of Sweet syndrome with myelodysplasia syndrome]. AB - OBJECTIVE: To study the clinical, histopathological and therapeutic features of Sweet syndrome with myelodysplastic syndrome (MDS). METHODS: The clinical data of 3 patients with Sweet syndrome and MDS diagnosed at Peking Union Medical College Hospital between October 1988 and November 2015 were reviewed. The laboratory test results, histopathological findings, and therapeutic regimens of these patients were analyzed retrospectively. RESULTS: The three cases were 29, 49 and 49 years old, respectively, including 2 females and 1 male. Two patients presented with Sweet syndrome before the onset of MDS, the other one patient developed Sweet syndrome and MDS simultaneously. The rash of all of these patients manifested as red painful papules in face, trunk and limbs, as well as edematous plaques and nodules. Histopathological examination of skin confirmed the diagnosis of Sweet syndrome. Complete blood count showed cytopenia of at least one lineage. Bone marrow cytology showed dysplasia of hematopoietic cells with abnormal high proportion of myeloblasts. Bone marrow pathology results were normal in 2 patients, while hypoplasia of hematopoietic tissue with excess adipose tissue was found in 1 patient. All the patients were treated with corticosteroid or immunosuppressants and skin lesions alleviated. But relapse was common in process of corticosteroid reduction. CONCLUSIONS: Sweet syndrome may be a precursor of MDS. The clinical manifestations, histopathological and hematological findings of these rare cases are characteristic. Corticosteroid indicates short-term response. The patients who had recurrent skin lesions should be further examined to exclude MDS. PMID- 27356644 TI - [Clinical application of different sedation regimen in patients with septic shock]. AB - OBJECTIVE: To evaluated the 3 sedation regimen for patients with septic shock. METHODS: The randomized controlled trial wan conducted. Forty-five patients with septic shock were assigned to 3 groups (midazolam group, propofol group, and dexmedetomidine group) randomly. The basic characteristics of patients, the duration of mechanical ventilation, the length of stay in the ICU, the death rate for 28 days and the regulatory cell (Treg) in peripheral blood were observed. The control group for Treg test was consisted of 20 healthy volunteers. RESULTS: There were no significant differences between the groups in the death rate for 28 days and the duration of mechanical ventilation. The length of stay in the ICU in dexmedetomidine group was shorter than that in midazolam group(15.21+/-5.55 vs.19.67+/-5.7 days, P<0.05). The Treg of 3 groups was higher than that of control group (11.82+/-4.93 vs.3.69+/-1.71, 11.30+/-3.42 vs. 3.69+/-1.71, 12.83+/ 6.17 vs. 3.69+/-1.71) at the first day of ICU. The Treg after 3 ICU days in dexmedetomidine group and the Treg after 5 ICU days in propofol group and in midazolam group have no difference with control group. CONCLUSION: For the patients with septic shock, dexmedetomidine could decrease the length of stay in the ICU and the duration of immune suppression. PMID- 27356645 TI - [Galpha11 expression and effect of sildenafil in muscularization of non-muscular pulmonary arterioles in rat with pulmonary arterial hypertension]. AB - OBJECTIVE: To investigate expression changes and role of Galpha11 protein in the processes of muscularization of non-muscular pulmonary arterioles and effect of sildenafil intervention in rats with pulmonary arterial hypertension (PAH). METHODS: Thirty SD rats were randomly divided into three groups, including normal control group, monocrotaline (MCT) group and sildenafil group; PAH model was prepared with 50 mg/kg MCT treatment for 4 weeks in the MCT group, and these rats were treated by 25 mg/kg sildenafil for 2 weeks after PAH formation in the sildenafil group, and the normal control group were treated with the equal amounts of physiological saline instead of monocrotaline; pulmonary artery pressure was measured with jugular vein catheterization; hematoxylin and eosin (HE) staining method was used to detect the pulmonary arteriolar morphology and vascular tissue parameters; expression of the target Galpha11 protein, vascular smooth muscle marker osteopontin (OPN) and proliferation marker proliferating cell nuclear antigen (PCNA) was detected by Western blot. RESULTS: Pulmonary artery mean pressure (mPAP), non-muscular pulmonary arterioles wall thickness index (TI) and area index (AI) of the MCT group were higher than those of the normal control group[(27.43+/-3.97) vs (11.93+/-1.52) mmHg (1 mmHg=0.133 kPa), 0.49+/-0.07 vs 0.31+/-0.09 and 0.74+/-0.05 vs 0.45+/-0.10](all P<0.05), and meanwhile the expression levels of Galpha11 and the related proteins including OPN and PCNA were significantly enhanced. mPAP, TI and AI[(18.59+/-1.44) mmHg, 0.39+/-0.09 and 0.56+/-0.04]of the sildenafil group were all lower than those of the MCT group (all P<0.05), and furthermore, expressions of Galpha11, OPN and PCNA also reduced in line with these changes. CONCLUSION: Galpha11 protein plays a role in the development of PAH and pulmonary non-muscular arteriole muscularization, and sildenafil effectively suppresses PAH and pulmonary vascular remodeling by inhibiting Galpha11 expression. PMID- 27356646 TI - [Analysis of clinical characteristics of necrotizing enterocolitis in term infants]. AB - OBJECTIVE: To investigate the characteristics and outcomes of necrotizing enterocolitis (NEC) in Chinese term infants population. METHODS: A national neonatal necrotizing enterocolitis network was established. Neonates as having necrotizing enterocolitis with gestation age >=37 weeks were identified if they met the accepted diagnostic criterion during the study period from Jan 1(st) 2011 to Dec 31(st) 2011. The data of maternal and neonates' characteristics, the comorbidities, the clinical interventions prior to NEC, the clinical courses and radiology results, the medical and surgical treatment and the outcomes were collected. SPSS 19.0 software was used to do statistic analysis. Logistic regression models were used to analyze the risk factors for death in infants with NEC, odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS: There were 231 067 newborn infants, 164 307 of them were term infants, admitted to 95 hospitals in main land China. There were 718 term infants were diagnosed as necrotizing enterocolitis with the incidence of 0.44%. There were 294 term infants cases identified as >=stage 2 necrotizing enterocolitis for the analysis, including 193 cases of stage 2 and 101 cases of stage 3.The mean gestation age was (39.0+/-1.3) weeks, and the mean birth weight was(3 087.4+/-548.3)g. The percentage of small for gestation age was 20.4%. The onset age of NEC was 5 (2 11)d. The percentage of cases received breast milk feeding was 23.7%. The most common comorbidities were sepsis (9.5%, 28/294), asphyxia (9.5%, 28/294), pneumonia (7.8%, 23/294) and congenital megacolon (7.5%, 22/294). The bowel perforation rate was 13.9%. The rate of cases who received surgical treatment was 25.2%(76.6% small intestinal necrosis and 65.8% small intestinal perforation). The mortality rate was 28.9%(the mortality rate were 20.7% and 44.6% in stage 2 and stage 3 NEC, respectively). Noninvasive continuous positive airway pressure treatment for NEC (OR=5.278, 95% CI: 2.058-13.533, P<0.01) and NEC staging 3 (OR=3.156, 95% CI: 1.766-5.642, P<0.01) were statistically significantly associated with mortality of NEC. CONCLUSIONS: The term infants with necrotizing enterocolitis usually have the underlying comorbidities. The breastmilk feeding rate is low. Necrotizing enterocolitis remains high mortality in term neonates in Chinese neonatal units. Noninvasive continuous positive airway pressure treatment for NEC is statistically significantly associated with mortality of NEC. PMID- 27356647 TI - [Safety and efficacy of preoperative induction therapy using a single high dose ATG-F in renal transplantation: a meta-analysis of randomized controlled trials]. AB - OBJECTIVE: This study aimed to evaluate the safety and efficacy of preoperative induction therapy using a single high dose (9 mg/kg) of antithymocyte globulin Fresenius S (ATG-F) for patients undergoing renal transplantation. METHODS: Randomized controlled clinical trials (RCTs) on the safety and efficacy of preoperative induction therapy using a single high dose of ATG-F for patients undergoing renal transplantation were searched in Cochrane Library, PubMed, EMBASE covering a period from the beginning of databases to July 2015. The meta analysis was conducted using RevMan 5.2. RESULTS: Five RCTs with 346 patients were included in this study. The meta-analysis showed that the incidences of acute rejection for the patients with renal transplantation were 20.6% (37/180) in the induction therapy group using a single high dose of ATG and 42.8% (71/166) in the control group, with a combined relative risk (RR) of 0.49 and 95% confidence interval (CI) of[0.36, 0.69](P<0.000 1). The patient survival rate (1 year: RR=1.02, 95% CI[0.98, 1.06], P=0.43; 5 years: RR=1.01, 95% CI[0.94, 1.08], P=0.83) and the graft survival rate (RR=1.04, 95% CI[0.97, 1.12], P=0.24) of the two groups were similar. The incidences of CMV infection, urinary tract infection, and malignant tumor were also similar in the two groups. CONCLUSION: The induction therapy using a single high dose of ATG-F significantly reduced the incidence of acute rejection after transplantation and showed no increased incidence of urinary tract infection, CMV infection, or malignant tumor. The results of our meta-analysis suggest that the application of a high dose of ATG-F may be a safe and effective induction therapy. PMID- 27356648 TI - Altered fibrin clot structure in patients with atrial fibrillation and worsening renal function. PMID- 27356649 TI - Evidence-based neurosurgery. Basic concepts for the appraisal and application of scientific information to patient care (Part II). AB - Medical evidence is obtainable from approaches, which might be descriptive, analytic and integrative and ranked into levels of evidence, graded according to quality and summarized into strengths of recommendation. Sources of evidence range from expert opinions through well-randomized control trials to meta analyses. The conscientious, explicit, and judicious use of current best evidence in making decisions related to the care of individual patients defines the concept of evidence-based neurosurgery (EBN). We reviewed reference books of clinical epidemiology, evidence-based practice and other previously related articles addressing principles of evidence-based practice in neurosurgery. Based on existing theories and models and our cumulative years of experience and expertise conducting research and promoting EBN, we have synthesized and presented a holistic overview of the concept of EBN. We have also underscored the importance of clinical research and its relationship to EBN. Useful electronic resources are provided. The concept of critical appraisal is introduced. PMID- 27356650 TI - New advances in prevention of migraine. Review of current practice and recent advances. AB - Despite being one of the most common disabling primary headaches, migraine continues to be underdiagnosed and under-treated. A migraine challenges not only the patient suffering from the migraine, but also physicians; especially in recognizing candidates for prophylaxis and selecting the appropriate preventive medication. Recently, there have been major advances in the diagnosis and treatment of migraine, with different guidelines of migraine management across the world. Here, we review migraines abortive and prophylactic medications, based on their pharmacologic category, citing their recommended doses, efficacy, and side effects. Additionally, we highlight the prophylactic treatment of specific patient populations and present suggested treatment approaches in view of recent international treatment guidelines that consider factors other than drug efficacy when choosing the optimal preventive therapy. Finally, we introduce drugs in different stages of development, which have novel mechanisms of action or have new therapeutic targets. PMID- 27356652 TI - The availability of services for children with autism spectrum disorder in a Saudi population. AB - OBJECTIVE: To assess the perceived availability of various services provided by Autism centers in our region. METHODS: A cross sectional study was conducted from March to May 2015 involving health care workers at various governmental and private autism centers in Jeddah, Kingdom of Saudi Arabia. A structured 30-item questionnaire was designed to assess their demographics, training, experience, and the availability of various services at their centers. RESULTS: Twelve autism centers were included and 136 employees participated in the study. Seventy-eight (57%) participants indicated that their center lacked important and essential services. These included programs for home care and outreach (59%), family recognition incentives and rewards (51%), integrative educational programs (39%), and occupational therapy (16%). Access for outside referral for these services was available in only 24% of cases. They cited several major obstacles in providing adequate service including; family involvement (24%), child's behavioral problems (13%), increased number of students (9%), and work environment and space (5%). CONCLUSION: Significant deficiencies exist in the availability of autism services in our region. Access for referrals for important services is also limited. We identified several areas that can be targeted to help develop, promote, and improve the provided services for children with autism spectrum disorder. PMID- 27356651 TI - Anti-glutamic acid decarboxylase antibody positive neurological syndromes. AB - A rare kind of antibody, known as anti-glutamic acid decarboxylase (GAD) autoantibody, is found in some patients. The antibody works against the GAD enzyme, which is essential in the formation of gamma aminobutyric acid (GABA), an inhibitory neurotransmitter found in the brain. Patients found with this antibody present with motor and cognitive problems due to low levels or lack of GABA, because in the absence or low levels of GABA patients exhibit motor and cognitive symptoms. The anti-GAD antibody is found in some neurological syndromes, including stiff-person syndrome, paraneoplastic stiff-person syndrome, Miller Fisher syndrome (MFS), limbic encephalopathy, cerebellar ataxia, eye movement disorders, and epilepsy. Previously, excluding MFS, these conditions were calledhyperexcitability disorders. However, collectively, these syndromes should be known as "anti-GAD positive neurological syndromes." An important limitation of this study is that the literature is lacking on the subject, and why patients with the above mentioned neurological problems present with different symptoms has not been studied in detail. Therefore, it is recommended that more research is conducted on this subject to obtain a better and deeper understanding of these anti-GAD antibody induced neurological syndromes. PMID- 27356653 TI - Saudi addiction therapeutic communities:Are they implementing the essential elements of addiction therapeutic communities. AB - OBJECTIVE: To investigate whether Saudi therapeutic communities (TCs) implement essential elements of TCs. METHODS: This is a cross sectional study where the author visited all of the Saudi addiction TCs between September and December 2014. At least one week was spent in each TC, attending many therapeutic activities, reviewing patient files and program documents, and interviewing directors, treating teams and residents. At the end of each visit, a short version of the Survey of Essential Elements Questionnaire (SEEQ) was conducted, which is a reliable tool to evaluate the essential elements of TCs. RESULTS: In 2014, there were only 5 TCs in Saudi Arabia. All of them were traditional TCs for adult male residents. The average total score was 3.72 out of 5 on the SEEQ. Regarding the 6 dimensions of the SEEQ, the TCs scored 4.15 on the TC perspective, 3.72 on the agency treatment approach and structure, 4.40 on community as therapeutic agent, 2.60 on educational and work activities, 3.50 on formal therapeutic elements, and 4.3 on process. There were no significant differences in dimensions scores among the 5 Saudi TCs. CONCLUSION: In general, all of the Saudi TCs scored fairly high on the SEEQ, which may reflect a sufficient implementation of the TC as a therapeutic model. Educational and work activities lagged behind the other dimensions and should be improved and reevaluated. PMID- 27356654 TI - Efficacy and safety of levetiracetam in the management of seizures in neonates. AB - OBJECTIVE: To evaluate the efficacy and safety of levetiracetam (LEV) in the management of seizures in neonates. METHODS: A prospective non-blind, single arm clinical trial conducted in the Department of Neonatology and Pediatric Intensive Care, Mohamad Kermanshahi, and Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran from May 2014 to December 2014. Fifty out of 60 newborns with gestational age >/=30 weeks with clinically diagnosed seizures were included. Levetiracetam was administered orally with an initial dose of 10 mg/kg twice a day. The patients were observed continuously by Neuro Intensive Care nurses, and visited daily by a neuropediatrician in the first 7 days and then at days 14, 30, and 90 after the start of LEV administration. Clinical examination was performed for every patient, and seizure number, antiepileptic medication, and adverse events were detailed at every visit. RESULTS: 47 infants were seizure free under LEV at the end of the first week, 47 remained seizure free at 4 weeks, and 46 remained seizure free at 11 weeks. No immediate and long term side effects were noted in our patients. CONCLUSION: This study investigated the efficacy and safety of LEV in neonatal seizure control but confirmation with further randomized controlled trials is required. PMID- 27356655 TI - Endovascular treatment of distal posterior inferior cerebellar artery aneurysms. AB - OBJECTIVE: To assess the feasibility and results of endovascular treatment for ruptured distal posterior inferior cerebellar artery (PICA) aneurysms. METHODS: We retrospectively reviewed our experience and results with endovascular treatments for a series of 13 consecutive patients with ruptured distal PICA aneurysms at the Southwest Hospital, Chongqing, China, treated between June 2011 and January 2015. Therapeutic considerations, intraoperative complications, and results were evaluated. RESULTS: Endovascular embolization was performed in all 13 patients including selective coiling (4), stentassisted coiling (2), microcatheter-assisted coiling (1), coiling without adjunctive techniques (1), and parent artery occlusion (5). Planed stent deployment failure occurred in one patients resulting from marked stenosis at the origin of the PICA; the patient's existing partial Wallenberg's syndrome became worse after treatment. Another 2 patients treated with parent artery occlusion recovered well without developing obvious neurological deficits, although a small cerebellar infarction of the distal PICA was observed. No patient experienced post procedural hemorrhage during the follow-up period (8-46 months; mean, 26.8 months). CONCLUSION: Distal PICA aneurysms can be managed effectively with various endovascular methods. Protective strategies using a stent or microcatheter for preserving the patency of the proximal PICA segment are a viable treatment option in reducing the potential risk of brain stem ischemia in selected patients. PMID- 27356656 TI - Neurological complications of bariatric surgery. AB - OBJECTIVE: To review and analyze the neurological complications from bariatric surgery in Kingdom of Saudi Arabia. METHODS: This cross sectional study was carried out in King Abdulaziz Medical City, Jeddah, Kingdom of Saudi Arabia from January 2009 to December 2015. Important personal and clinical data were collected from the charts of the patients who underwent bariatric surgery. Data on follow up visit and remote complication if present, was also collected. All patients with neurological complications were reviewed in detail. The significant difference was calculated by using T-test and p-value<0.05 was considered significant. RESULTS: A total of 451 patients underwent bariatric surgery, 15 cases had neurological complications (3%). Axonal polyneuropathy was the most frequent neurological complication, but cases of Wernicke syndrome, vitamin B12 deficiency, Guillain-Barre syndrome and copper deficiency were also identified. Fourteen patients (93.3%) had full recovery from the neurological signs and symptoms; one patient died. CONCLUSION: Bariatric surgery is not free of potential neurological complications. Complications may affect both central and peripheral nervous system and death is a possibility. Multidisciplinary care including consultation of different teams is highly recommended. PMID- 27356657 TI - Risk factors and subtypes of acute ischemic stroke. A study at King Fahd Hospital of the University. AB - OBJECTIVE: To identify the different subtypes of acute ischemic stroke, and estimate the frequency of various risk factors among these patients. METHODS: In this retrospective, cross-sectional study, we reviewed the medical records of patients admitted with the diagnosis of acute ischemic stroke at King Fahd Hospital of the University, Al-Khobar, Saudi Arabia from March 2008 till December 2015. The demographic characteristics, subtypes of stroke, risk factors (hypertension, diabetes mellitus, hyperlipidemia, coronary artery disease, atrial fibrillation, valvular heart disease) and other relevant data were documented on pre-defined data sheets. RESULTS: The records of 343 patients were included in the study; 64.4% were male and 35.6% were female. The mean age was 59.3+/-13.6 (mean+/-SD) years for males, and 66.8+/-14.9 years for females. Small vessel occlusion was the most common etiologic subtype of ischemic stroke (32.1%), followed by cardio embolic (21.9%), and large artery atherosclerosis (14.6%). The middle cerebral artery was the most commonly affected territory. Hypertension was found in 78.1%, diabetes mellitus in 62.7%, hyperlipidemia in 54.8%, and ischemic heart disease in 24.2% of patients. CONCLUSION: Small vessel occlusion was the most common etiology in our cohort. The onset of stroke at a relatively younger age group in the male population is of great concern and needs to be verified by further epidemiological studies. Adequate control of modifiable risk factors may help in reducing the disease burden caused by stroke. PMID- 27356659 TI - Ipsilateral hemiparesis and contralateral lower limb paresis caused by anterior cerebral artery territory infarct. AB - Ipsilateral hemiparesis is rare after a supratentorial stroke, and the role of reorganization in the motor areas of unaffected hemisphere is important for the rehabilitation of the stroke patients. In this study, we present a patient who had a subclinical remote infarct in the right pons developed ipsilateral hemiparesis and contralateral lower limb paresis caused by a new infarct in the left anterior cerebral artery territory. Our case suggests that the motor areas of the unaffected hemisphere might be reorganized after stroke, which is important for the rehabilitation of stroke patients. PMID- 27356658 TI - Acute psychosis in children: do not miss immune-mediated causes. AB - New-onset psychosis in children represents a complex presenting symptom. Psychosis can be attributable to a combination of factors and etiologies, and all possible causes must be systematically examined. There is growing evidence that a proportion of psychosis/ psychiatric manifestations in children may be immunemediated, and physicians should consider this etiology in each presentation of first-episode psychosis. Immunemediated encephalopathies/encephalitis are increasingly being recognized in children with antibodies to N-methyl-D-aspartate receptor, Leucine-rich gliomainactivated 1 or other central nervous system antigens such as Contactin-associated protein-like 2, glutamic acid decarboxylase, alpha-amino-3-hydroxy-5-methyl-4isoxazolepropionic acid or Gamma aminobutyric acid B. In this study, we describe 3 cases of immune-mediated encephalopathy/encephalitis with prominent psychiatric symptoms at presentation, and suggest a practical diagnostic and treatment approach for children with acute psychosis of an immune-mediated cause. PMID- 27356660 TI - Conus medullaris stroke. Does F wave predict return of ambulation? AB - Absent F wave in the stage of spinal shock has been described in cases of traumatic spinal cord injury. The role of F wave in predicting prognosis after conus medullaris infarct has not been described. We describe herein a middle aged man with a conus medullaris infarct. Both tibial and peroneal F waves were absent on day 4. The left tibial F wave reappeared in the following study on day 18. All F waves reappeared on day 56 at which time the patient was still wheelchair bound. He regained walking on day 105. We hypothesize that reappearance of initially absent F waves post conus medullaris infarct is a good prognostic sign for the return of ambulation. The applicability of this observation requires further research. We also discuss clinical and diagnostic caveats in this case. PMID- 27356662 TI - State of clinical neuroscience research in Saudi Arabia: where do we rank in the world? PMID- 27356661 TI - Patterns of antiepileptic drugs use in epileptic pediatric patients in Jordan. AB - OBJECTIVE: To determine prescribing patterns of antiepileptic drugs (AEDs) in pediatric patients with confirmed diagnosis of epilepsy, and to provide knowledge of general practice of physicians. METHODS: The study was a multi-center crosssectional observational study, in specialized clinics for management of epilepsy in north, central and south Jordan. This study was conducted from January 2014 to July 2014. These were 3 from university tertiary care hospitals and 4 from governmental tertiary care hospitals. RESULTS: A total of 694 pediatric patients were included. Monotherapy AED use had the highest frequency 465 (67.0%), followed by dual therapy 162 (23.3%). The frequency of monotherapy in university hospitals was lower than governmental hospitals (p<0.05); however, Polytherapy was more frequent in younger children. Two old AEDs were most frequently prescribed as a monotherapy; Valproic acid 235 (50.5%) and carbamazepine 155 (33.3%). The most common combination in dual therapy was valproic acid with carbamazepine 28 (17.3%). The second most common combinations were carbamazepine with levetiracetam 21 (13.0%) or valproic acid with levetiracetam 20 (12.3%). CONCLUSION: Older AED remain first line drugs for use in both monotherapy and combination therapy for epileptic disorders. Polytherapy is associated with younger kids and being treated in a university hospital. PMID- 27356663 TI - Cerebral fat embolism syndrome following total knee replacement causing a devastating neurocognitive sequelae. PMID- 27356664 TI - Methanol intoxication with cerebral hemorrhage. PMID- 27356665 TI - A diagnostic riddle in an immunocompetent adult: Meningioma or intracranial fungal granuloma? PMID- 27356666 TI - Incidence of autism in high risk neonatal follow up. PMID- 27356667 TI - Infections with the Sexually Transmitted Pathogen Nosema apis Trigger an Immune Response in the Seminal Fluid of Honey Bees (Apis mellifera). AB - Honey bee (Apis mellifera) males are highly susceptible to infections with the sexually transmitted fungal pathogen Nosema apis. However, they are able to suppress this parasite in the ejaculate using immune molecules in the seminal fluid. We predicted that males respond to infections by altering the seminal fluid proteome to minimize the risk to sexually transmit the parasite to the queen and her colony. We used iTRAQ isotopic labeling to compare seminal fluid proteins from infected and noninfected males and found that N. apis infections resulted in significant abundance changes in 111 of the 260 seminal fluid proteins quantitated. The largest group of proteins with significantly changed abundances consisted of 15 proteins with well-known immune-related functions, which included two significantly more abundant chitinases in the seminal fluid of infected males. Chitinases were previously hypothesized to be involved in honey bee antifungal activity against N. apis. Here we show that infection with N. apis triggers a highly specific immune response in the seminal fluid of honey bee males. PMID- 27356669 TI - Observation of Evidence for the pi*-sigma* Hyperconjugation in the S1 State of o , m-, and p-Fluorotoluenes by Double-Resonance Infrared Spectroscopy. AB - Drastic changes of the methyl internal rotation potential energy functions upon the electronic excitation have been reported for o- and m-fluorotolunes [ Okuyama , K. , Mikami , N. , and Ito , M. J. Phys. Chem. 1985 , 89 , 5617 - 5625 ], and their physical origin has been attributed to the pi*-sigma* hyperconjugation. To observe direct evidence of the pi*-sigma* hyperconjugation, double-resonance infrared spectroscopy was carried out in the CH stretching vibrational region in both the S0 and S1 states of jet-cooled o-, m-, and p-fluorotoluenes. In the spectra of both o- and m-fluorotoluenes, some of the methyl CH bands were red shifted upon the electronic excitation while the residual CH bands stayed in the same frequency region. The normal-mode analysis demonstrated that the shift behavior correlates to the relative conformation between the methyl CH bond and the phenyl ring plane. This conformation-dependent methyl CH bond weakening clearly supports the presence of the pi*-sigma* hyperconjugation in o- and m fluorotoluenes. The similar red-shift of the methyl CH bands upon the electronic excitation was seen also in p-fluorotoluene though the magnitude of the shift was much smaller. The mechanism of its internal rotation potential energy behavior, however, can be different from those of the o- and m-isomers. PMID- 27356668 TI - Decreasing the ratio of matriptase/HAI-1 by downregulation of matriptase as a potential adjuvant therapy in ovarian cancer. AB - Tumor invasion and metastasis are complex biological processes. Matriptase and its endogenous inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1) are involved in invasion and metastasis. To evaluate the ratio of matriptase/HAI 1 and their potential therapeutic value in ovarian cancer, HO-8910 human ovarian cancer cells and the homologous high-metastatic HO-8910PM cells were used as in vitro cellular models ovarian cancer. The invasive and metastatic abilities, and the expression of matriptase and HAI-1 in these cells were detected using scratch assays, Transwell chamber assays, reverse transcription-quantitative polymerase chain reaction, western blotting and fluorescent immunocytochemistry. Following infection with lentivirus-mediated matriptase-targeting small interfering RNA (siRNA), cell cycle progression and apoptosis were also analyzed. The migration distance and number of invading HO-8910PM cells were significantly increased compared with HO-8910 cells. HO-8910PM cells exhibited a significantly higher ratio of matriptase/HAI-1 mRNA levels compared with HO-8910 cells (0.51 vs. 0.24, ~2.2 fold increase). Compared with HO-8910 cells, the matriptase mRNA level was increased by ~3.6 fold in HO-8910PM cells, whereas the HAI-1 mRNA level was increased by ~1.7 fold. Similar increases in protein expression levels were also observed in HO-8910PM cells compared with HO-8910 cells. Migration and invasiveness were positively correlated with matriptase expression level (r=0.994, P<0.01) and the ratio of matriptase/HAI-1 (r=0.929, P<0.01). Downregulation of matriptase using siRNA resulted in inhibition of the invasive and metastatic abilities of HO-8910PM cells, cell cycle arrest in the G0/G1 phase and increased apoptosis. The present study demonstrated that ovarian cancer cell metastasis and invasion were more dependent on upregulation of matriptase levels than downregulation of HAI-1. Matriptase may be a potential adjuvant therapeutic target for inhibiting ovarian cancer invasion and metastasis. PMID- 27356670 TI - Glasgow Blatchford, pre-endoscopic Rockall and AIMS65 scores show no difference in predicting rebleeding rate and mortality in variceal bleeding. AB - OBJECTIVE: To compare the performance of the Glasgow Blatchford score (GBS), pre endoscopic Rockall score (PRS) and AIMS65 score in predicting specific clinical endpoints following variceal upper gastrointestinal hemorrhage (UGIH). MATERIAL AND METHODS: Between January 2008 and December 2013, we retrospectively analyzed 225 consecutive hospitalized patients managed for endoscopically confirmed UGIH. RESULTS: A total of 225 patients (mean age 61.3 years), mostly diagnosed with alcoholic cirrhosis (195/86.7%), presented with variceal UGIH during the study period. Rebleeding occurred in 22 (9.8%) patients and 30-day mortality was 39 (17.3%). Initial hemostasis was achieved with N-butyl cyanoacrylate (151/79.1%) and endoscopic variceal ligation (40/20.9%), while secondary rebleeding prophylaxis in 110 (48.9%) patients was accomplished using endoscopic variceal ligation (92%). The majority of patients died from the underlying disease, while 12 (30.8%) died from bleeding. Median hospital stay was 6 (1-35) days. There was no statistically significant difference among AIMS65, GBS and PRS in predicting mortality (AUROC 0.70 vs. 0.64 vs. 0.66) or rebleeding rates (AUROC 0.74 vs. 0.60 vs. 0.67). The GBS was superior in predicting the need for blood transfusion compared to AIMS65 score (AUROC 0.75 vs. 0.61, p = 0.01) and PRS (AUROC 0.75 vs. 0.58, p = 0.009). CONCLUSIONS: The AIMS65, GBS and PRS scores are comparable but not useful for predicting outcome in patients with variceal UGIH because of poor discriminative ability. The GBS is superior in predicting the need for transfusion compared to AIMS65 score and PRS. PMID- 27356671 TI - Airway Centric(r) TMJ philosophy/Airway Centric(r) orthodontics ushers in the post-retraction world of orthodontics. AB - OBJECTIVE: Airway Centric(r) Dentistry/Orthodontics was defined in a previous article (Gelb M. Airway centric TMJ philosophy. CDA Journal. 2014) that also suggested airway considerations were more important than condylar position issues in determining patient health and welfare. Indeed, that article called for a new paradigm in the profession, but specific treatment techniques to achieve optimal airways and avoid reducing the airway were not discussed. The present article amplifies on that article and identifies specific orthodontic treatment methods, which are or are not, congruent with this new paradigm. METHOD: The basis of traditional orthodontic diagnosis is outlined with references from the literature that show the scientific foundation for treatment is weak. A new approach to diagnosis and treatment with the goal of airway optimization is discussed. DISCUSSION: Six keys for optimal orthodontic outcomes are presented as new goals, and none involve the teeth. Ten specific treatment goals are outlined, and some are the diametric opposite of the current standard of care in the profession. CONCLUSION: We recommend that optimizing the airway for every patient and never doing any treatment which will diminish the airway, even minutely, needs to become the standard of care in Airway Centric(r) Dentistry. PMID- 27356672 TI - [A qualitative analysis of spelling mistakes and a systematic supportive learning instruction of spelling disorder]. AB - This paper explains how a qualitative analysis of spelling mistakes (Oldenburger Fehleranalyse, Thome & Thome, 2014) may be used to select learning materials according to individual needs. The pre-post design with control group serves to evaluate the effects of an intervention that is systematic and learning supportive for pupils with a diagnosed spelling disorder (ages 12 to 14; 6th-8th grade). Therapists of the experimental group were instructed to apply a series of linguistic and psycholinguistic criteria when creating the material for instruction and when carrying out the therapy. Therapists of the control group carried out the intervention without attending to these criteria, although they did have knowledge about the pupil's profile in spelling mistakes. The intervention included 20 sessions. The ANOVA shows improvement for both groups (HSP, May 2012): (F(1, 14) = 15,05, p = .002, eta2 = .518). For the experimental group it is stronger, and the difference in achievement gain is significant (F(1, 14) = 4,70, p = .048; eta2 = .25). These results support a combination of qualitative analysis and a high qualification for therapists that relates specifically to orthography and its instruction. For some pupils the changes in the qualitative profiles reveal persistent support requirements in phonology or grammar instruction. PMID- 27356673 TI - [Does the Youth Psychopathic Traits Inventory (YPI) identify a clinically relevant subgroup among young offenders?]. AB - Objective: Does the Youth Psychopathic Traits Inventory identify one or more high risk subgroups among young offenders? Which recommendations for possible courses of action can be derived for individual clinical or forensic cases? Method: Model based cluster analysis (Raftery, 1995) was conducted on a sample of young offenders (N = 445, age 14-22 years, M = 18.5, SD = 1.65). The resulting model was then tested for differences between clusters with relevant context variables of psychopathy. The variables included measures of intelligence, social competence, drug use, and antisocial behavior. Results: Three clusters were found (Low Trait, Impulsive/Irresponsible, Psychopathy) that differ highly significantly concerning YPI scores and the variables mentioned above. The YPI Scores Delta Low = 4.28 (Low Trait - Impulsive/Irresponsible) and Delta High = 6.86 (Impulsive/Irresponsible - Psychopathy) were determined to be thresholds between the clusters. Conclusions: The allocation of a person to be assessed within the calculated clusters allows for an orientation of consequent tests beyond the diagnosis of psychopathy. We conclude that the YPI is a valuable instrument for the assessment of young offenders, as it yields clinically and forensically relevant information concerning the cause and expected development of psychopathological behavior. PMID- 27356674 TI - [Prevention of dyslexia - short-term and intermediate effects of promoting phonological awareness and letter-sound correspondence with at-risk preschool children]. AB - Objective: This study assesses the short-term and intermediate effects of preschool training stimulating phonological awareness and letter-sound correspondence for children at risk of developing dyslexia. Moreover, we examined whether training reduced the frequency of subsequent dyslexic problems. Method: 25 children at risk of developing dyslexia were trained with Horen, Lauschen, Lernen 1 und 2 (Kuspert & Schneider, 2008; Plume & Schneider, 2004) by their kindergarten teachers and were compared with 60 untrained at-risk children. Results: The training revealed a significant short-term effect: The phonological awareness of trained at-risk children increased significantly over that of untrained at-risk children. However, there were no differences in phonological awareness, spelling, and reading ability between the first-graders in the training and control group. Furthermore, reading problems were reduced in the training group. Conclusions: In the future, phonological awareness as well as additional predictors should be included when identifying children vulnerable to developing dyslexia. Moreover, in order to prevent dyslexia, additional prerequisite deficits need to be identified, alleviated, and their effects evaluated. PMID- 27356675 TI - [Parent-child interaction therapy (PCIT)]. AB - Parent-child interaction therapy (PCIT), a manualized evidence-based intervention, was originally developed to treat disruptive behavior problems in children aged 2-6 years. It is also considered to be an evidence-based intervention for physical abuse among children. Moreover, PCIT has proved to be effective for attention deficit hyperactivity disorder, autism spectrum disorder, separation anxiety disorder, and depression. Thus, it could become the first evidence-based, transdiagnostic intervention method for 2-6-year-old children. PCIT is based on attachment theory as well as learning theory, combining aspects of play therapy and behavior therapy. It consists of two treatment phases: child directed interaction (CDI) and parent-directed interaction (PDI). In both phases parents are taught special skills. When interacting with their child parents practice these skills and are live coached by the therapist. CDI aims at improving the parent-child relationship and is the basis for PDI. In CDI, parents learn to follow their child's lead as long as the child shows appropriate behavior. In PDI, parents practice effectively taking the lead wherever necessary. On average, it takes about 15-20 sessions to complete PCIT, which can be terminated as soon as the parents demonstrate a mastery of the skills, when child disruptive behavior has been reduced to clearly normal levels, and when the parents have become confident in managing child behavior on their own. PMID- 27356676 TI - [Attention and reading performance in children with ADHD, reading disorder and the combined condition]. AB - Attention Deficit Hyperactivity Disorder (ADHD) and Dyslexia co-occur more often than expected by chance. Both disorders can have severe negative impact on children's development. The aim of the present study was to compare attention and reading performance in children with ADHD, dyslexia and the comorbid condition. Ninety-nine German children in 3rd and 4th grade with ADHD (n = 26), dyslexia (n = 22) and the comorbid condition (n = 24) compared to a healthy control group (n = 27) were assessed with a model oriented assessment battery for reading and attention. Additionally, comorbid problems were examined. Children with ADHD were characterized by difficulties in decoding and reading comprehension, while children with dyslexia showed impairments in their attentional performance. Psychometric data revealed that children with dyslexia showed both externalizing and internalizing symptoms, while children with the comorbid condition scored the highest on all psychopathological dimensions. The results suggest, that reading problems in children with ADHD might be an epiphenomenon of the task used dependent on time constraints inherent to the task. Impairments of attentional functions in children with dyslexia emphasize the importance of a sufficient diagnostic procedure for subclinical ADHD symptoms as possible comorbid disorder. Future studies should focus the impact of early treatment of attentional deficits on reading acquisition. PMID- 27356677 TI - [Modular psychotherapy with children and adolescents]. AB - The implementation of evidence-based psychotherapy with children and adolescents has been limited so far. This is mainly due to the fact that patients in service settings tend to have higher rates of comorbidities and more frequently changing therapy needs than those in research settings. Thus, modular psychotherapies are promising, as they allow the treatment protocol to be adapted to patients' individual needs. Because no review on modular psychotherapy for children and adolescents exists, we conducted a systematic literature research. The results of the 15 randomized controlled trials identified demonstrate that modular psychotherapy is associated with significant reductions in symptom levels as well as with higher rates of diagnostic remission compared to control conditions. Because of the lack of evidence, future studies should investigate the incremental efficacy of modular approaches and test the validity of underlying theoretical models as well as of decision flowcharts. Modular psychotherapy approaches have the potential to personalize evidence-based interventions for children and adolescents across various therapeutical traditions, and to facilitate their implementation into clinical practice. PMID- 27356678 TI - Basic numerical processing, calculation, and working memory in children with dyscalculia and/or ADHD symptoms. AB - Objective: Deficits in basic numerical skills, calculation, and working memory have been found in children with developmental dyscalculia (DD) as well as children with attention-deficit/hyperactivity disorder (ADHD). This paper investigates cognitive profiles of children with DD and/or ADHD symptoms (AS) in a double dissociation design to obtain a better understanding of the comorbidity of DD and ADHD. Method: Children with DD-only (N = 33), AS-only (N = 16), comorbid DD+AS (N = 20), and typically developing controls (TD, N = 40) were assessed on measures of basic numerical processing, calculation, working memory, processing speed, and neurocognitive measures of attention. Results: Children with DD (DD, DD+AS) showed deficits in all basic numerical skills, calculation, working memory, and sustained attention. Children with AS (AS, DD+AS) displayed more selective difficulties in dot enumeration, subtraction, verbal working memory, and processing speed. Also, they generally performed more poorly in neurocognitive measures of attention, especially alertness. Children with DD+AS mostly showed an additive combination of the deficits associated with DD-only and A_Sonly, except for subtraction tasks, in which they were less impaired than expected. Conclusions: DD and AS appear to be related to largely distinct patterns of cognitive deficits, which are present in combination in children with DD+AS. PMID- 27356679 TI - Paraneoplastic autoantibody panels: sensitivity and specificity, a retrospective cohort. AB - BACKGROUND: Experts in the autoimmune paraneoplastic field recommend autoantibody testing as "panels" to improve the poor sensitivity of individual autoantibodies in detecting paraneoplastic neurological syndromes (PNS). The sensitivity of those panels was not reported to date in a fashion devoid of incorporation bias. We aimed to assess the collective sensitivity and specificity of one of the commonly used panels in detecting PNS. METHODS: A single-centered retrospective cohort of all patients tested for paraneoplastic evaluation panel (PAVAL; test ID: 83380) over one year for the suspicion of PNS. Case adjudication was based on newly proposed diagnostic criteria in line with previously published literature, but modified to exclude serological status to avoid incorporation bias. Measures of diagnostic accuracy were subsequently calculated. Cases that failed to show association with malignancy within the follow-up time studied, reflecting a possibly pure autoimmune process was considered paraneoplastic-like syndromes. RESULTS: Out of 321 patients tested, 51 patients tested positive. Thirty-two patients met diagnostic criteria for paraneoplastic/paraneoplastic-like syndromes. The calculated collective sensitivity was 34% (95% CI: 17-53), specificity was 86% (95% CI: 81-90), Youden's index 0.2 and a positive clinical utility index 0.07 suggesting poor utility for case-detection. CONCLUSION: This is the first reported diagnostic accuracy measures of paraneoplastic panels without incorporation bias. Despite recommended panel testing to improve detection of PNS, sensitivity remains low with poor utility for case-detection. The high-calculated specificity suggests a possible role in confirming the condition in difficult cases suspicious for PNS, when enough supportive evidence is lacking on ancillary testing. PMID- 27356681 TI - Provisional Cessation of Acceptance of Submissions to the APJCP on June 30th and Transfer of Chief Editor Responsibilities. PMID- 27356680 TI - Turkish Cypriot paternal lineages bear an autochthonous character and closest resemblance to those from neighbouring Near Eastern populations. AB - BACKGROUND: Cyprus is an island in the Eastern Mediterranean Sea with a documented history of human settlements dating back over 10,000 years. AIM: To investigate the paternal lineages of a representative population from Cyprus in the context of the larger Near Eastern/Southeastern European genetic landscape. SUBJECTS AND METHODS: Three hundred and eighty samples from the second most populous ethnic group in Cyprus (Turkish Cypriots) were analysed at 17 Y chromosomal short tandem repeat (Y-STR) loci. RESULTS: A haplotype diversity of 0.9991 was observed, along with a number of allelic variants, multi-allelic patterns and a most frequent haplotype that have not previously been reported elsewhere. Pairwise genetic distance comparisons of the Turkish Cypriot Y-STR dataset and Y-chromosomal haplogroup distribution with those from Near East/Southeastern Europe both suggested a closer genetic connection with the Near Eastern populations. Median-joining network analyses of the most frequent haplogroups also revealed some evidence towards in situ radiation. CONCLUSION: Turkish Cypriot paternal lineages seem to bear an autochthonous character and closest genetic connection with the neighbouring Near Eastern populations. These observations are further underscored by the fact that the haplogroups associated with the spread of Neolithic Agricultural Revolution from the Fertile Crescent (E1b1b/J1/J2/G2a) dominate (>70%) the Turkish Cypriot haplogroup distribution. PMID- 27356682 TI - Curcumin: a Polyphenol with Molecular Targets for Cancer Control. AB - Curcumin, is a polyphenol from Curcuma longa (turmeric plant), is a polyphenol that belongs to the ginger family which has long been used in Ayurveda medicines to treat various diseases such as asthma, anorexia, coughing, hepatic diseases, diabetes, heart diseases, wound healing and Alzheimer's. Various studies have shown that curcumin has anti-infectious, anti-inflammatory, anti-oxidant, hepatoprotective, thrombosuppressive, cardio protective, anti-arthritic, chemo preventive and anti-carcinogenic activities. It may suppress both initiation and progression stages of cancer. Anticancer activity of curcumin is due to negative regulation of inflammatory cytokines, transcription factors, protein kinases, reactive oxygen species (ROS) and oncogenes. This review focuses on the different targets of curcumin to treat cancer. PMID- 27356683 TI - Cancer Research Advance in CKLF-like MARVEL Transmembrane Domain Containing Member Family (Review). AB - CKLF-like MARVEL transmembrane domain-containing family (CMTM) is a novel family of genes first reported at international level by Peking University Human Disease Gene Research Center. The gene products are between chemokines and the transmembrane-4 superfamily. Loaceted in several human chromosomes, CMTMs, which are unregulated in kinds of tumors, are potential tumor suppressor genes consisting of CKLF and CMTM1 to CMTM8. CMTMs play important roles in immune, male reproductive and hematopoietic systems. Also, it has been approved that CMTM family has strong connection with diseases of autoimmunity, haematopoietic system and haematopoietic system. The in-depth study in recent years found the close relation between CMTMs and umorigenesis, tumor development and metastasis. CMTM family has a significant clinical value in diagnosis and treatment to the diseases linking to tumor and immune system. PMID- 27356684 TI - Etiopathogenesis of Gastric Cancer. AB - Gastric cancer is a multifactorial and complex malignant disease seen commonly worldwide. It is one of the few malignant conditions in which the etiology involves infectious agents (Helicobacter pylori), but there are many other risk factors incuding high salt intake. Its pathogenesis generally involves interactions between environmental factors and genetic disposition. It is currently onsidered that stem cells may play a central role in gastric cancer development. PMID- 27356685 TI - Melanoma in Iran: a Retrospective 10-Year Study. AB - BACKGROUND: Melanoma, the most life-threatening type of skin cancer, is a malignant tumor initiating in melanocytes that rapidly metastasizes and causes death. MATERIALS AND METHODS: In this retrospective study, samples were selected from patients' information files in our Cancer Institute in Tehran with a designed checklist. A total of 322 files were found from 2003 until 2012. Then the raw data were transferred to Statistical Package for Social Sciences (SPSS) software version 16 and additional analysis was performed by Students t-test. The important variables were considered according to the available information from history of pathology including age, gender, occupation, stage and location of tumor. RESULTS: Our data showed that incidence of melanoma has been different in the studied 10-year period according to age. Also, incidence of melanoma was higher in men than women. It was more common in lower limbs. More commonly housewives among women and farmers among men were affected by melanoma. CONCLUSIONS: Taken together the descriptive data clarified general aspects of this disease for further screening and interventions. PMID- 27356686 TI - Hypermethylation Status of E-Cadherin Gene in Gastric Cancer Patients in a High Incidence Area. AB - Gastric cancer (GC) is the fourth most prevalant cancer and the second leading cause of cancer-related mortality worldwide. As in other cancers gastric carcinogenesis is multifactorial involving environmental, genetic and epigenetic components. Epigenetic silencing due to hypermethylation of tumour suppressor genes is one of the key events in gastric carcinogenesis. This study was aimed to analyse the hypermethylation status of the E-Cadherin (CDH1) gene promoter in GCs in the ethnic Kashmiri population. In this study a total of 80 GC patients were recruited. Hypermethylation in tumour tissue was detected by methylation specific PCR (MS-PCR). Hypermethylation of CDH1 promoter was observed in 52 (65%) of gastric carcinoma cases which was significantly much higher than adjacent normal tissue [p<=0.0001]. Further the frequency of CDH1 promoter methylation was significantly different with intestinal and diffuse types of gastric cancer [55.7% vs 82.1%; <0.05]. Moreover females and cases with lymph node invasion had higher frequencies of CDH1 hypermethylation [P<=0.05]. Thus the current data indicate a vital role of epigenetic alteration of CDH1 in the causation and development of gastric cancer, particularly of diffuse type, in our population. PMID- 27356687 TI - Raw Fish Consuming Behavior Related to Liver Fluke Infection among Populations at Risk of Cholangiocarcinoma in Nakhon Ratchasima Province, Thailand. AB - Opisthorchiasis is a health problem in rural communities of Thailand, particularly in the northeast and north regions. Therefore, this study aimed to investigate raw fish consuming behavior related to liver fluke infection among the population at risk for opisthorchiasis and cholangiocarcinoma (CCA). A cross sectional descriptive study was conducted in Meuang Yang district, Nakhon Ratchasima province, northeast Thailand, between June and October 2015. Participants were screened for CCA, and samples who had a high score of CCA risk were purposively selected. A predesigned questionnaire was utilized to collect the data from all participants. X2-test was used for analysis of associations between demographic data and raw fish consumption. The results revealed that participants had past histories of stool examination (33.0%), liver fluke infection (21.0%), praziquantel use (24.0%), raw fish consumption (78.0%), relatives family consuming raw fish (73.0%), and relatives family with CCA (3.0%). Participants consumed several dished related to liver fluke infection, mainly raw fermented fish (13.0%), under smoked catfish (5.00%), raw pickled fish (4.00%), and raw spicy minced fish salad (3.00%). The most common types of cyprinoid fish were Barbodes gonionotus (39%), Hampala dispar (38%), Puntius brevis (37%), Cyclocheilichthys armatus (33%), Puntioplites proctozysron (32%), and Luciosoma bleekeri (30%), respectively. Participants had a low level of knowledge (mean=3.79, SD=0.74), moderate attitude (mean=7.31, SD=7.31) and practice (mean=38.64, SD=6.95) regarding liver fluke prevention and control. Demographic variables like age (>36 years old; X2-test=17.794, p-value=0.001), education (primary school; X2-test=18.952, p-value=0.001), marital status (married; X2-test=12.399, p-value=0.002), and income (<5,000 baht; X2 test=27.757, p-value=0.015) were significantly associated with raw fish consumption. This result indicates that the population had risk consumption for liver fluke infection particularly of various cyprinoid fishes that are 2nd intermediate hosts. Therefore, health education is required to improve their behavior. PMID- 27356688 TI - Microglial Contribution to Glioma Progression: an Immunohistochemical Study in Eastern India. AB - Human glioma, arising from glial cells of the central nervous system, accounts for almost 30%of all brain tumours , neoplasms with a poor prognosis and high mortality rates worldwide. In the present study we assessed tissue architectural modifications associated with macrophage lineage cells, controversial major immune effector cells within the brain, in human glioma tissue samples from eastern India. Ethically cleared post-operative human glioma samples from our collaborative neurosurgery unit with respective CT/MRI and patient history were collected from the Nodal Centre of Neurosciences in Kolkata, over 9 months. Along with conventional histopathology, samples were subjected to silver-gold staining and fluorescence tagged immunophenotyping for the detection of electron dense brain macrophage/microglia cells in glioma tissue, followed by immune-phenotyping of cells. With higher grades, CD11b+/Iba-1+ macrophage/microglia architecture with de-structured boundaries of glioma lesions indicated malfunction and invasive effector state. Present study documented a contribution of microglia to glioma progression in Eastern India. PMID- 27356689 TI - Diagnostic Performance of Whole-Body Diffusion-Weighted Imaging Compared to PET CT Plus Brain MRI in Staging Clinically Resectable Lung Cancer. AB - BACKGROUND: Precise staging of lung cancer is usually evaluated by PET-CT and brain MRI. Recently, however, whole-body diffusion-weighted magnetic resonance imaging (WB-DWI) has be applied. The aim of this study is to determine whether the diagnostic performance of lung cancer staging by WB-DWI is superior to that of PET-CT+brain MRI. MATERIALS AND METHODS: PET-CT + brain MRI and WB-DWI were used for lung cancer staging before surgery with 59 adenocarcinomas, 16 squamous cell carcinomas and 6 other carcinomas. RESULTS: PET-CT + brain MRI correctly identified the pathologic N staging in 67 patients (82.7%), with overstaging in 5 (6.2%) and understaging in 9 (11.1%), giving a staging accuracy of 0.827. WB-DWI correctly identified the pathologic N staging in 72 patients (88.9%), with overstaging in 1 (1.2%) and understaging in 8 patients (9.9%), giving a staging accuracy of 0.889. There were no significant differences in accuracies. PET-CT + brain MRI correctly identified the pathologic stages in 56 patients (69.1%), with overstaging in 7 (8.6%) and understaging in 18 (22.2%), giving a staging accuracy of 0.691. WB-DWI correctly identified the pathologic stages in 61 patients (75.3%), with overstaging in 4 (4.9%) and understagings in16(19.7%), giving a staging accuracy of 0.753. There were no significant difference in accuracies. CONCLUSIONS: Diagnostic efficacy of WB-DWI for lung cancer staging is equivalent to that of PET-CT + brain MRI. PMID- 27356690 TI - Matrix Metalloproteinase-13 - A Potential Biomarker for Detection and Prognostic Assessment of Patients with Esophageal Squamous Cell Carcinoma. AB - BACKGROUND: Matric metalloproteinase (MMP) 13 gene expression is increased in esophageal squamous cell carcinomas (ESCCs) and associated with increasing tumor invasion, lymph node involvement and decreased survival rates. Levels of the circulating enzyme may be elevated and used as a marker of tumor progression. In this study, clinical application of MMP-13 serum levels was evaluated for early detection, prediction of prognosis and survival time of ESCC patients. MATERIALS AND METHODS: Serum levels of MMP13 were determined by ELISA in 66 ESCC patients prior of any treatment and 54 healthy controls for comparison with clinicopathological data through statistical analysis with Man Whitney U and Log Rank tests. In addition, clinical value of MMP13 levels for diagnosis was evaluated by receiver operating characteristic (ROC) test. RESULTS: The serum level of MMP-13 in patients (>250 pg/ml) was significantly higher than in the control group (<100 pg/ml) (p value=0.004). Also the results showed a significant correlation between MMP-13 serum levels with tumor stage (p value = 0.003), depth of tumor invasion (p value=0.008), involvement of lymph nodes (p value = 0.011), tumor size (p value = 0.018) and survival time. While there were no significant correlation with grade and location of tumors. ROC analysis showed that MMP-13 level is an accurate diagnostic marker especially to differentiate pre-invasive/ invasive lesions from normal controls (sensitivity and specificity: 100%). CONCLUSIONS: These findings indicate a potential clinical significance of serum MMP13 measurement for early detection and prognostic assessment in ESCC patients. PMID- 27356691 TI - Oncogenic Activation of Fibroblast Growth Factor Receptor-3 and RAS Genes as Non Overlapping Mutual Exclusive Events in Urinary Bladder Cancer. AB - BACKGROUND: Urinary bladder cancer is a common malignancy in the West and ranks as the 7th most common cancer in our region of Kashmir, India. FGFR3 mutations are frequent in superficial urothelial carcinoma (UC) differing from the RAS gene mutational pattern. The aim of this study was to analyze the frequency and association of FGFR3 and RAS gene mutations in UC cases. MATERIALS AND METHODS: Paired tumor and adjacent normal tissue specimens of 65 consecutive UC patients were examined. DNA preparations were evaluated for the occurrence of FGFR3 and RAS gene mutations by PCR-SCCP and DNA sequencing. RESULTS: Somatic point mutations of FGFR3 were identified in 32.3% (21 of 65). The pattern and distribution were significantly associated with low grade/stage (<0.05). The overall mutations in exon 1 and 2 in all the forms of RAS genes aggregated to 21.5% and showed no association with any clinic-pathological parameters. In total, 53.8% (35 of 65) of the tumors studied had mutations in either a RAS or FGFR3 gene, but these were totally mutually exclusive in and none of the samples showed both the mutational events in mutually exclusive RAS and FGFR3. CONCLUSIONS: We conclude that RAS and FGFR3 mutations in UC are mutually exclusive and non-overlapping events which reflect activation of oncogenic pathways through different elements. PMID- 27356692 TI - Histomorphology and Immunohistochemistry of Gastrointestinal Stromal Tumors in a Malaysian Population. AB - PURPOSE: To study histomorphological and immunohistochemical patterns of gastro intestinal stromal tumours (GISTs) in Malaysia. MATERIALS AND METHODS: A total of 29 GIST cases from Hospital Tuanku Ja'afar, Seremban ,were studied retrospectively over a period of 10 years from January 2002 to December 2011. Patient demographic data like age, sex and etnicity were collected. Tumour characteristics like site, maximum dimension and specimen type were analysed. Evaluation was according to established criteria into very low, low, intermediate and high-risk categories. Immunohistochemical characteristics were also analysed. RESULTS: The mean age of patients was 59.7 years. Males (59%) were found to be more commonly affected than females (41%). The Chinese (45%) were commonly affected than Malays (41%), and Indians (10%). The most common symptom was pain in the abdomen (13.8%). More than half of the cases were seen in stomach (53%). The tumour size ranged from 1.5 cm to 17 cm with a mean of 6.94cm. Microscopic findings revealed that the spindle cell type was the most common (76%). It was observed that the majority of the cases (48%) were categorised in the intermediate risk group. Immunohistochemical staining showed positivity for CD117 (78.6%), CD34 (71.4%), vimentin (86.2%), S-100 (27.6%), SMA (35.7%), PKC THETA (46.4%) and PDGRFA (67.9%). PMID- 27356693 TI - High Occurrence of Non-Clear Cell Renal Cell Carcinoma in Oman. AB - It is conventionally accepted that renal cell carcinoma (RCC) occurs in older patients and the clear cell type is the most common histology. However, ethnic variations exist and this study was carried out to determine the epidemiological pattern of RCC in Oman. Ninety RCC patients who presented to a tertiary care center in the Sultanate of Oman from 2010 to 2014 were studied. The main findings were that the median age of presentation was low, more patients presented with localized stage, and there was a higher incidence of non-clear (especially papillary) histology. Data from other Gulf countries and possible reasons for the different profile are discussed. PMID- 27356694 TI - Clinical Prognostic Score for Predicting Disease Remission with Differentiated Thyroid Cancers. AB - BACKGROUND: Differentiated thyroid cancer is the most common endocrine malignancy with a generally good prognosis. Knowing long-term outcomes of each patient helps management planning. The study was conducted to develop and validate a clinical prognostic score for predicting disease remission in patients with differentiated thyroid cancer based on patient, tumor and treatment factors. MATERIALS AND METHODS: A retrospective cohort study of 1,217 differentiated thyroid cancer patients from two tertiary-care hospitals in the Northeast of Thailand was performed. Associations between potential clinical prognostic factors and remission were tested by Cox proportional-hazards analysis in 852 patients (development cohort). The prediction score was created by summation of score points weighted from regression coefficients of independent prognostic factors. Risks of disease remission were estimated and the derived score was then validated in the remaining 365 patients (validation cohort). RESULTS: During the median follow-up time of 58 months, 648 (76.1%) patients in the development cohort had disease remission. Five independent prognostic factors were identified with corresponding score points: duration from thyroid surgery to 131I treatment (0.721), distant metastasis at initial diagnosis (0.801), postoperative serum thyroglobulin level (0.535), anti-thyroglobulin antibodies positivity (0.546), and adequacy of serum TSH suppression (0.293). The total risk score for each patient was calculated and three categories of remission probability were proposed: <=1.628 points (low risk, 83% remission), 1.629-1.816 points (intermediate risk, 87% remission), and >=1.817 points (high risk, 93% remission). The concordance (C-index) was 0.761 (95% CI 0.754-0.767). CONCLUSIONS: The clinical prognostic scoring model developed to quantify the probability of disease remission can serve as a useful tool in personalized decision making regarding treatment in differentiated thyroid cancer patients. PMID- 27356695 TI - Polymorphisms of XRCC1 and XRCC2 DNA Repair genes and Interaction with Environmental Factors Influence the Risk of Nasopharyngeal Carcinoma in Northeast India. AB - Multiple genetic and environmental factors have been reported to play key role in the development of nasopharyngeal carcinoma (NPC). Here, we investigated interactions of XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms and environmental factors in modulating susceptibility to NPC in Northeast India. One hundred NPC patients, 90 first-degree relatives of patients and 120 controls were enrolled in the study. XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms were determined using PCR-RFLP, and the results were confirmed by DNA sequencing. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approaches were applied for statistical analysis. The XRCC1 Gln/Gln genotype showed increased risk (OR=2.76; <0.024) of NPC. However, individuals with both XRCC1 and XRCC2 polymorphic variants had 3.2 fold elevated risk (<0.041). An enhanced risk of NPC was also observed in smoked meat (OR=4.07; P=0.004) and fermented fish consumers (OR=4.34, P=0.001), and tobacco-betel quid chewers (OR=7.00; P=0.0001) carrying XRCC1 polymorphic variants. However, smokers carrying defective XRCC1 gene showed the highest risk (OR = 7.47; <0.0001). On MDR analysis, the best model for NPC risk was the five-factor model combination of XRCC1 variant genotype, fermented fish, smoked meat, smoking and chewing (CVC=10/10; TBA=0.636; <0.0001); whereas in interaction entropy graphs, smoked meat and tobacco chewing showed synergistic interactions with XRCC1. These findings suggest that interaction of genetic and environmental factors might increase susceptibility to NPC in Northeast Indian populations. PMID- 27356696 TI - Adoption and Implementation of Tobacco Control Policies in Schools in India: Results of the Bihar School Teachers Study. AB - Implementation of no tobacco policies in schools is associated with lower tobacco use among teachers and students. In this study we assessed the extent that a school-based intervention for teachers resulted in adoption and implementation of tobacco control policies. From a random sample of government schools (8th-10th), 72 were randomized into intervention and control conditions. Intervention included health education programs for teachers and support for tobacco control policy implementation. Adoption and implementation of policies were assessed at baseline and immediately after intervention. All 36 intervention and one control school adopted a tobacco-control policy. Higher enforcement of tobacco-control policy was at post intervention (OR=3.26; CI: 2.35, 4.54) compared to baseline in intervention schools. Some 64% of intervention and 28% control schools showed "improvement" in policy implementation. Adoption and implementation of no tobacco policies was positively impacted by intervention. This study provides support for scaling up of school-based tobacco control interventions to promote school tobacco control policies. PMID- 27356697 TI - Mortality Attributable to Second Hand Smoking in Morocco: 2012 Results of a National Prevalence Based Study. AB - PURPOSE: To estimate the number of deaths attributable to second hand smoking (SHS) in Morocco in 2012. MATERIALS AND METHODS: prevalence based study focusing on mortality from ischaemic heart disease (IHD) and lung cancer among non-smokers aged 35 and over. Prevalence of SHS among never smokers was gathered from a national cross sectional survey on tobacco and population attributable risk (PAR) was calculated by applying PARs to mortality. The analyses were stratified by sex, age and area of exposure. RESULTS: Rates for exposure to SHS among men aged 35-64 years ranged from 20.0% at home to 57.4% at work. Among non-smoking Moroccans aged 35 and over, 233 (IC: 147 - 246) deaths were attributable to exposure to SHS; 156 (IC: 100 - 221) in women and 77 (IC: 44 -125) in men. A total of 173 (122 - 222) deaths were estimated to have been caused by exposure only at home, 34 (9 - 76) by exposure only at the work place and 26 (15 - 58) by exposure both at home and work places. Exposure to SHS could be responsible for 182 (128 - 237) deaths from IHD and 51 (19 - 109) from lung cancer. CONCLUSIONS: These data confirm that SHS needs urgent attention in Morocco. PMID- 27356698 TI - Risk Perception and Correlates of Tobacco Use among Young People Outside of Formal School Settings in Lagos State, Nigeria. AB - BACKGROUND: Tobacco use among youth is a major public health problem. Youth outside of formal school settings are often understudied but may be at increased risk. MATERIALS AND METHODS: A descriptive cross- sectional study was carried out among 326 young people aged 15-24 years in four randomly selected motor parks in Lagos state. Interviewer-administered questionnaires were used to collect data. RESULTS: The mean age of the respondents was 21.0+/-2.3yrs. Many 252 (77.3%) dropped out before the end of the third year of secondary schooling. The majority were aware that active (78.2%), and passive smoking (77.3%) are harmful to health. Nearly two-thirds of the respondents disagreed with an outright ban of cigarettes (63.2%) and restriction of cigarette sales to persons below 18 years (67.9%) while 254 (66.8%) supported a ban on tobacco smoking in enclosed public places. One hundred and fifty (46.0%) respondents had experimented with smoking of which 106 (32.5%) had progressed to become current smokers. Half of the current smokers, 54 (50.9%), felt the need for a cigarette first thing in the morning. A multivariate analysis for smoking initiation, showed that for every increasing year of age, respondents were 1.08 times more likely to have initiated cigarette smoking; males and respondents who lived alone or with peers were 2.34 times and 1.77 times more likely to have initiated smoking respectively; those who consume alcohol and marijuana were 7.27 and 1.89 times respectively more likely to have initiated smoking while those who consumed alcohol were 6.17 times more likely to be current smokers. PMID- 27356699 TI - Evaluation of Delhi Population Based Cancer Registry and Trends of Tobacco Related Cancers. AB - BACKGROUND: Tobacco use is the single most important preventable risk factor for cancer. Surveillance of tobacco-related cancers (TRC) is critical for monitoring trends and evaluating tobacco control programmes. We analysed the trends of TRC and evaluated the population-based cancer registry (PBCR) in Delhi for simplicity, comparability, validity, timeliness and representativeness. MATERIALS AND METHODS: We interviewed key informants, observed registry processes and analysed the PBCR dataset for the period 1988-2009 using the 2009 TRC definition of the International Agency for Research on Cancer. We calculated the percentages of morphologically verified cancers, death certificate-only (DCO) cases, missing values of key variables and the time between cancer diagnosis and registration or publication for the year 2009. RESULTS: The number of new cancer cases increased from 5,854 to 15,244 (160%) during 1988-2009. TRC constituted 58% of all cancers among men and 47% among women in 2009. The age-adjusted incidence rates of TRC per 100,000 population increased from 64.2 to 97.3 among men, and from 66.2 to 69.2 among women during 1988-2009. Data on all cancer cases presenting at all major government and private health facilities are actively collected by the PBCR staff using standard paper-based forms. Data abstraction and coding is conducted manually following ICD-10 classifications. Eighty per cent of cases were morphologically verified and 1% were identified by death certificate only. Less than 1% of key variables had missing values. The median time to registration and publishing was 13 and 32 months, respectively. CONCLUSIONS: The burden of TRC in Delhi is high and increasing. The Delhi PBCR is well organized and generates high quality, representative data. However, data could be published earlier if paper based data are replaced by electronic data abstraction. PMID- 27356700 TI - Past Trends and Future Estimation of Annual Breast Cancer Incidence in Osaka, Japan. AB - BACKGROUND: Although the breast cancer incidence rate in Japan is lower than in western countries, the age-specific rates have markedly increased in recent years, along with the problems of declining birth rate and an aging population. MATERIALS AND METHODS: We examined past trends of age-specific breast cancer incidence using data from the Osaka Cancer Registry from 1976 to 2010, and estimated future trends until 2025 based on the changes observed and population dynamics using a log linear regression model. RESULTS: The age-specific breast cancer incidence rate has increased consistently from the 1970s, and the rates have caught up with those of Japanese-Americans in the US. Assuming the increasing tendency of age-specific breast cancer incidence to be constant, the average annual incidence of breast cancer will increase 1.7-fold from 2006-2010 to 2021-2025. Furthermore, the number of patients aged 80 years should increase 3.4-fold. CONCLUSIONS: The medical demand for breast cancer care in Japan may increase explosively in the future, particularly among the elderly. We need to prepare for such a future increase in demand for care, although careful monitoring is needed to confirm these results. PMID- 27356701 TI - Limited Impact of Music Therapy on Patient Anxiety with the Large Loop Excision of Transformation Zone Procedure - a Randomized Controlled Trial. AB - BACKGROUND: Many studies have pointed to strategies to cope with patient anxiety in colposcopy. Evidence shows that patients experienced considerable distress with the large loop excision of transformation zone (LLETZ) procedure and suitable interventions should be introduced to reduce anxiety. This study aimed to investigate the effects of music therapy in patients undergoing LLETZ. MATERIALS AND METHODS: A randomized controlled trial was conducted with patients undergoing LLETZ performed under local anesthesia in an out patient setting at Ramathibodi Hospital, Bangkok, Thailand, from February 2015 to January 2016. After informed consent and demographic data were obtained, we assessed the anxiety level using State Anxiety Inventory pre and post procedures. Music group patients listened to classical songs through headphones, while the control group received the standard care. Pain score was evaluated with a visual analog scale (VAS). Statistical analysis was conducted using Pearson Chi-square, Fisher's Exact test and T-Test and p-values less than 0.05 were considered statistically significant. RESULTS: A total of 73 patients were enrolled and randomized, resulting in 36 women in the music group and 37 women in the non-music control group. The preoperative mean anxiety score was higher in the music group (46.8 VS 45.8 points). The postoperative mean anxiety scores in the music and the non music groups were 38.7 and 41.3 points, respectively. VAS was lower in music group (2.55 VS 3.33). The percent change of anxiety was greater in the music group, although there was no significant difference between two groups. CONCLUSIONS: Music therapy did not significantly reduce anxiety in patients undergoing the LLETZ procedure. However, different interventions should be developed to ease the patients' apprehension during this procedure. PMID- 27356702 TI - High Prevalence of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection in Thailand. AB - BACKGROUND: Chronic hepatitis B (CHB) infection is one of the important causes of hepatocellular carcinoma (HCC) in Thailand, involved in the pathogenesis and leading to a development of HCC with or without cirrhotic changes of the liver. This study was aimed to investigate the predictive factors for HCC among CHB patients in a tertiary care center in Thailand. MATERIALS AND METHODS: We conducted a retrospective study of CHB patients with or without HCC during the period of January 2009 and December 2014 at Thammasat University Hospital, Pathumthani, Thailand. Data on clinical characteristics, biochemical tests and radiologic findings were collected from review of medical records. RESULTS: A total of 266 patients were diagnosed with CHB in Thammasat university hospital during the study period. However, clinical information of only 164/266 CHB patients (98 males, 66 females with mean age of 49.4 years) could be completely retrieved in this study. The prevalence of HCC in CHB infection in this study was 38/164 (23.2%). CHB patients with HCC had a mean age older than those without HCC (59.5 vs 47 years, P-value = 0.01). Furthermore, history of upper GI bleeding, tattooing, blood transfusion, and chronic alcoholism were significantly more common in CHB patients with HCC than patients without HCC (13.2% vs 3.2% P-value 0.03, OR = 4.6, 95%CI = 1.2-18.1, 20% vs 3.9%, P-value = 0.01, OR= 6.1, 95% CI= 1.6-23.6, 20% vs 6.3%, P-value = 0.03, OR = 3.8, 95%CI =1.1-12.7, 62.2% vs 30.3%, P-value <0.0001, OR = 3.7, 95%CI= 1.7-8.1 respectively). Interestingly, more CHB patients with HCC had evidence of cirrhosis than those without HCC (78.9% vs 20.4%, P-value <0.0001, OR = 14.6, 95%CI = 5.8-36.7). In CHB patients with HCC, surgical therapy provided longer survival than radiofrequency ablation (RFA) (72 vs 46.5 months, P-value= 0.04). The mean survival time after HCC diagnosis was 17.2 months. CONCLUSIONS: HCC remains a major problem among patients with CHB infection in Thailand. Possible risk factors are male gender, history of upper GI bleeding, chronic alcoholism, tattooing, blood transfusion and evidence of cirrhosis. For early stage HCC patients, surgical treatment provided longer survival time than RFA. Most HCC patients presented with advanced disease and had a grave prognosis. Appropriate screening of CHB patients at risk for HCC might be an appropriate approach for early detection and improvement of long-term outcomes. PMID- 27356703 TI - ssociation of Cytochrome P450-1B1 Gene Polymorphisms with Risk of Breast Cancer: an Egyptian Study. AB - It is thought that population characteristics of breast cancer may be due to a variation in the frequency of different alleles of genes such as CYP1B1. We aimed to determine the association of CYP1B1 polymorphisms in 200 breast cancer cases and 40 controls by PCR-RFLP. Frequencies were assessed with clinical and risk factors in Egyptian patients. The genotype LV and the Leu allele frequencies for patients and controls were 42.9% and 50%, and 52.9% and 53.3%, respectively), with no significant differences observed (P values = 0.8 and 0.6, respectively). There was also no significant association between genotypes and any risk factors for cases (>0.05) except laterality and metastasis of the tumor (P values=0.006 and 0.06, respectively). The CYP1B1 polymorphism Val432Leu was not associated with breast cancer in Egypt, but may provide clues for future studies into early detection of the disease. PMID- 27356704 TI - Endometrial Cancer in Hospital Universiti Sains Malaysia. AB - BACKGROUND: Endometrial cancer is the most common gynecological malignancy among females worldwide, approximately 320,000 women being diagnosed with the disease each year and 76,000 dying. To date, there is limited knowledge of endometrial cancer in Malaysia. OBJECTIVES: To identify the epidemiological profile and prognostic factors of survival. MATERIALS AND METHODS: A list of endometrial cancer patients in 2000-2011 was obtained from the hospital Record Department. Only cases confirmed by histopathology examination were included. We excluded those with incomplete medical records or referral cases. Simple and multiple Cox regression approaches were used for data analysis. RESULTS: Only 108 cases were included with a mean (SD) age of 62.7 (12.3) years, with 87.0% Malay ethnicity. Grade of cancer was: 29.1% grade 1, 43.7% grade 2 and 27.2% grade 3. The majority of patients had non-endometrioid type (60.2%), with myometrial invasion (82.2%) and lymphovascular invasion (57.3%). The significant prognostic factors were age (HR 1.05; 95% CI: 1.02, 1.08, p=0.002) and having lymphovascular invasion (HR 2.15; 95% CI: 1.08, 4.29; p=0.030). CONCLUSIONS: Endometrial cancer patients should be diagnosed earlier to reduce the risk of mortality. The public should be given education on the signs and symptoms of the disease. PMID- 27356705 TI - Effects of Group Training Based on the Health Belief Model on Knowledge and Behavior Regarding the Pap Smear Test in Iranian Women: a Quasi-Experimental Study. AB - The Pap smear test is recommended for early diagnosis of cervical cancer. The aim of this study was to assess knowledge and behavior regarding the Pap smear test based on the Health Belief Model (HBM) in women referred to premarital counseling classes, Hamadan, Iran. This quasi-experimental study was conducted on 330 women, who were allocated randomly to two case and control groups (n=165). Two educational session classes were performed in the case group. Two stages in before and after intervention groups were evaluated. Analysis of data was performed by SPSS/16.0, using t-test, x2, and McNemar's test. P-values <0.05 were regarded as significant. There was no significant difference between the mean scores of the various structures of this model in two groups before the intervention. However, after the intervention there were significant increase in mean score of knowledge and all variables of HBM in the intervention group(<0.001). The findings of this study highlight the important role of education about cervical cancer on changing women's beliefs about cervical screening. PMID- 27356706 TI - Risk Factors for Lung Cancer Mortality in a Referral Center. AB - BACKGROUND: Lung cancer is one of the most common causes of death that is rising in many countries including Iran. This study aimed to determine the impact of factors on survival of lung cancer patients at a referral center of lung diseases in Tehran, Iran. MATERIALS AND METHODS: A retrospective study was conducted on adult lung cancer cases admitted to a referral center for lung diseases from 2011 to 2015. Multivariate analysis was performed to determine the risk factors for all-cause mortality. RESULTS: Of a total 933 patients with lung cancer, 53.4% died, 49.3% of them at the hospital. Overall median follow-up time was 7 months. The most common histological type of cancer was adenocarcinoma with a 13 month median survival time. Age >=55 and smoking remained significant for all-cause mortality on Cox analysis, whereas gender was not. CONCLUSIONS: The survival of lung cancer patients is poor and the patients with history of smoking and age >=55 are at increased risk of death. Having a large hospital-based registry provides a good measurement of prognostic statistics for lung cancer. Further investigations are necessary to establish reasons for mortality. PMID- 27356707 TI - Garlic Phytocompounds Possess Anticancer Activity by Specifically Targeting Breast Cancer Biomarkers - an in Silico Study. AB - BACKGROUND: Breast cancer (BC) is a serious lifestyle disease. There are several prognostic biomarkers like nuclear receptors whose over-expression is associated with BC characteristics. These biomarkers can be blocked by compounds with anti cancer potential but selection must be made on the basis of no adverse side effects. This study is focused on finding of compounds from a plant source garlic. MATERIALS AND METHODS: Twenty compounds from garlic and five targets considered involved in BC were retrieved from Pubchem database and Protein Data Bank respectively. They were docked using Accelrys Discovery Studio (DS) 4.0. The compounds which showed interaction were checked for drug likeliness. RESULTS: Docking studies and ADMET evaluation revealed twelve compounds to be active against the targets. All the compounds displayed highly negative dock scores which indicated good interactions. CONCLUSIONS: The results of this study should help researchers and scientists in the pharmaceutical field to identify drugs based on garlic. PMID- 27356708 TI - Behavioral Modification Regarding Liver Fluke and Cholangiocarcinoma with a Health Belief Model Using Integrated Learning. AB - This study aimed to modify behavior regarding liver fluke and cholangiocarcinoma prevention in Chumphuang district, Nakhon Ratchasima province, Thailand through integrated learning. A total of 180 participants were included through purposive selection of high-risk scores on verbal screening. Participants attended the health education program which applied the health belief model included family based, knowledge station based, academic merit based and community based learning. Data were collected using a questionnaire composed of 4 parts: 1) personal information, 2) knowledge, 3) perceived susceptibility, severity, benefits, and barriers, 4) practice regarding liver fluke and cholangiocarcinoma prevention. The result revealed that the majority were female (79.9%), age >=60 years old (33.2%), primary school educational level (76.1%), and agricultural occupation (70.1%). The mean scores of knowledge, perception, and practice to liver fluke and cholangiocarcinoma prevention, before participated the integrative learning were low, moderate, and low, respectively. Meanwhile, the mean score of knowledge, perceived susceptibility, severity, benefits, and barriers, and practice regarding liver fluke and cholangiocarcinoma prevention, were higher with statistical significance after participation in the integrated learning. This finding indicates that health education programs may successfully modify health behavior in the rural communities. Therefore they may useful for further work behavior modification in other epidemic areas. PMID- 27356709 TI - Temporal Trends and Future Prediction of Breast Cancer Incidence Across Age Groups in Trivandrum, South India. AB - BACKGROUND: Increasing breast cancer (BC) incidence rates have been reported from India; causal factors for this increased incidence are not understood and diagnosis is mostly in advanced stages. Trivandrum exhibits the highest BC incidence rates in India. This study aimed to estimate trends in incidence by age from 2005- 2014, to predict rates through 2020 and to assess the stage at diagnosis of BC in Trivandrum. MATERIALS AND METHODS: BC cases were obtained from the Population Based Cancer Registry, Trivandrum. Distribution of stage at diagnosis and incidence rates of BC [Age-specific (ASpR), crude (CR) and age standardized (ASR)] are described and employed with a joinpoint regression model to estimate average annual percent changes (AAPC) and a Bayesian model to estimate predictive rates. RESULTS: BC accounts for 31% (2681/8737) of all female cancers in Trivandrum. Thirty-five percent (944/2681) are <50 years of age and only 9% present with stage I disease. Average age increased from 53 to 56.4 years (p=0.0001), CR (per 105 women) increased from 39 (ASR: 35.2) to 55.4 (ASR: 43.4), AAPC for CR was 5.0 (p=0.001) and ASR was 3.1 (p=0.001). Rates increased from 50 years. Predicted ASpR is 174 in 50-59 years, 231 in > 60 years and overall CR is 80 (ASR: 57) for 2019- 20. CONCLUSIONS: BC, mostly diagnosed in advanced stages, is rising rapidly in South India with large increases likely in the future; particularly among post-menopausal women. This increase might be due to aging and/or changes in lifestyle factors. Reasons for the increased incidence and late stage diagnosis need to be studied. PMID- 27356710 TI - What Do Korean Women Know and Want to Know about Thyroid Cancer? A Qualitative Study. AB - BACKGROUND: Despite increasing debate about overdiagnosis and overtreatment of thyroid cancer in Korea, information to guide decisions on whether or not to undergo screening for and treatment of abnormal lesions of the thyroid is lacking. Moreover, studies have yet to outline what lay people know and want to know about thyroid cancer. The primary aim of this study was to explore general awareness of thyroid cancer among Korean women, their sources of information, and their satisfaction with the information they are provided. The secondary aim was to investigate information needs about thyroid cancer. MATERIALS AND METHODS: A qualitative study using focus group interviews was conducted. Twenty-nine women were divided into four groups: (1) participants who had never undergone thyroid ultrasound screening; (2) those who had undergone screening, (3) those who continued to undergo regular check-ups with ultrasonography for benign nodules of the thyroid; and (4) participants who had undergone surgery for thyroid cancer. RESULTS: A widespread lack of awareness of information on thyroid cancer was noted among participants in groups 1 and 2 who were not well aware of thyroid cancer and generally recognized it as a'good cancer'. Surprisingly, instead of doctors and medical personnel, most participants reported obtaining information from acquaintances and media outlets. Moreover, most participants described dissatisfaction with their experience with screening and a lack of explanation on treatment and test results from medical personnel. CONCLUSIONS: Women in Korea seek reliable information on thyroid cancer that could help them to better understand the disease and make informed decisions regarding screening and treatment. More effort is needed from medical personnel to communicate the implications of thyroid cancer, screening results, and treatments thereof to lay people. PMID- 27356711 TI - Application of Immunophenotyping and Heteroduplex Polymerase Chain Reaction (hPARR) for Diagnosis of Canine Lymphomas. AB - BACKGROUND: Canine malignant lymphoma is classified into B- or T-cell origin, as in the human case. Due to differences in prognosis, a suitable method needs to be developed for lineage identification. AIMS: To determine the accuracy of immunophenotypic and molecular information between three methods: immunocytochemistry (ICC), immunohistochemistry (IHC) and heteroduplex polymerase chain reaction for antigen receptor rearrangements (hPARR) in spontaneous canine lymphomas. MATERIALS AND METHODS: Peripheral blood, fine needle aspiration and tissue biopsies from enlarged peripheral lymph nodes prior to treatment of 28 multicentric lymphoma patients were collected. Cytopathology and histopathology were examined and classified using the updated Kiel and WHO classifications, respectively. Anti-Pax5 and anti-CD3 antibodies as B- and T-cell markers were applied for immunophenotyping by ICC and IHC. Neoplastic lymphocytes from lymph node and white blood cell pellets from peripheral blood were evaluated by hPARR. RESULTS: In this study, low grade B-cell lymphoma accounted for 25% (7/28), high grade B-cell lymphoma for 64.3% (18/28) and high grade T-cell lymphoma for 10.7% (3/28). According to the WHO classification, 50% of all cases were classified as diffuse large B-cell lymphoma. In addition, ICC showed concordant results with IHC; all B-cell lymphomas showed Pax5+/CD3, and all T-cell lymphomas exhibited Pax5-/CD3+. In contrast to hPARR, 12 B-cell lymphomas featured the IgH gene; seven presented the TCRgamma gene; five cases showed both IgH and TCRgamma genes, and one case were indeterminate. Three T-cell lymphomas showed the TCRgamma gene. The percentage agreement between hPARR and ICC/IHC was 60%. CONCLUSIONS: Immunophenotyping should not rely on a single method. ICC or IHC with hPARR should be used concurrently for immunophenotypic diagnosis in canine lymphomas. PMID- 27356712 TI - Breast Conserving Therapy and Quality of Life in Thai Females: a Mixed Methods Study. AB - BACKGROUND: To explore factors that influence quality of life (QOL) in patients receiving breast conserving therapy (BCT). MATERIALS AND METHODS: In this sequential mixed methods study, 118 women from Songklanagarind Hospital were included. We used participants' characteristics, Body Image Scale (BIS), and Functional Assessment of Cancer Therapy with the Breast Cancer Subscale (FACT-B) for analysis. The BIS transformed into presence of body image disturbance (BID). Factors that influenced QOL were determined by stepwise multiple linear regression. Forty-one participants were selected for qualitative analysis. Our female researcher performed the semi-structured interviews with questions based on the symbolic interaction theory. Final codes were analysed using thematic analysis along with investigator triangulation methods. RESULTS: Ninety percent had early stage breast cancer with post-completed BCT, for an average of 2.7 years. The median BIS score and FACT-B score were 2 (IQR=10) and 130 (IQR=39). In the regression analysis, an age of more than 50 years and BID were significant factors. As for the value of conserved breasts, two themes emerged: a conserved breast is an essential part of a participant's life and also the representation of her womanhood; the importance of a breast is related to age. CONCLUSIONS: Body image influenced QOL in post BCT participants. The conserved breasts also lead to positive and better impact on their body image as an essential part of their life. PMID- 27356713 TI - Mate and Tea Intake, Dietary Antioxidants and Risk of Breast Cancer: a Case Control Study. AB - Recently, we reported an inverse association between high 'mate' intake (infusion of Ilex paraguariensis herb, a staple beverage in temperate South America) and breast cancer (BC) risk. Stronger inverse associations were found in high strata of tea, vegetable, fruit and energy intakes, and in overweight/obese women, suggesting possible roles for 'mate' mainly from its antioxidant contribution. The present study attempted to thoroughly explore possible associations among 'mate' and tea intake, dietary antioxidants and BC risk. Combining two databases of previous studies, 572 BC incident cases and 889 controls were interviewed with a specific questionnaire featuring socio-demographic, reproductive and lifestyle variables, and a food frequency questionnaire (64 items), focusing on 'mate' intake (consumer status, daily intake, age at start, age at quit, duration of habit). Food-derived nutrients were calculated from available databases. Odds ratios (OR) and their 95% confidence intervals were calculated through unconditional logistic regression, adjusting for relevant potential confounders. The highest 'mate' intake was significantly inversely associated with BC risk for both low and high carotenoids (OR=0.40 vs. 0.41), vitamin C (OR=0.33 vs. 0.50), vitamin E (OR=0.37 vs. 0.45), flavonols (OR=0.38 vs. 0.48) and reduced glutathione (OR=0.48 vs. 0.46) strata. High tea intake showed significant inverse risk associations only with high carotenoids (OR=0.41), vitamin E (OR=0.48) and reduced glutathione (OR=0.43) strata. In conclusion, a strong and inverse association for 'mate' intake and BC was found, independent of dietary antioxidant levels. Also strong inverse associations with tea intake were more evident only at high levels of certain dietary antioxidants. PMID- 27356714 TI - Association of Estrogen Receptor Alpha and Interleukin 6 Polymorphisms with Lymphovascular Invasion, Extranodal Extension, and Lower Disease-Free Survival in Thai Breast Cancer Patients. AB - Breast cancer is the most frequent type of cancer diagnosed among women worldwide and also in Thailand. Estrogen and estrogen receptors exert important roles in its genesis and progression. Several cytokines have been reported to be involved in the microenvironment that promotes distant metastasis via modulation of immune and inflammatory responses to tumor cells. Estrogen receptor genetic polymorphisms and several cytokines have been reported to be associated with breast cancer susceptibility and aggressiveness. To investigate roles of genetic polymorphisms in estrogen receptor alpha (ESR1) and interleukin 6 (IL6), breast cancer patients and control subjects were recruited from the Division of Head, Neck and Breast Surgery (Siriraj Hospital, Bangkok, Thailand). Polymorphisms in ESR1 (rs3798577) and IL6 (rs1800795 and rs1800797) were evaluated by real-time PCR in 391 breast cancer patients and 79 healthy controls. Associations between genetic polymorphisms and clinicopathological data were determined. There was no association between genetic polymorphisms and breast cancer susceptibility. However the ESR1 rs3798577 CT genotype was associated with presence of lymphovascular invasion (OR=2.07, 95%CI 1.20-3.56, p=0.009) when compared to the TT genotype. IL6 rs1800795 CC genotype was associated with presence of extranodal extension (OR= 2.30, 95%CI 1.23-4.31, p=0.009) when compared to the GG genotype. Survival analysis showed that IL6 rs1800797 AG or AA genotypes were associated with lower disease-free survival. These findings indicate that polymorphisms in ESR1 and IL6 contribute to aggressiveness of breast cancer and may be used to identify high risk patients. PMID- 27356715 TI - Head to Head Comparison of the Chun Nomogram, Percentage Free PSA and Primary Circulating Prostate Cells to Predict the Presence of Prostate Cancer at Repeat Biopsy. AB - BACKGROUND: The limitations of total serum PSA values remain problematic, especially after an initial negative prostate biopsy. In this prospective study of Chilean men with a continued suspicion of prostate cancer due to a persistently elevated total serum PSA, abnormal digital rectal examination and initial negative prostate biopsy were compared with the use of the on-line Chun nomagram, detection of primary malignant circulating prostate cells (CPCs) and free percent PSA to predict a positive second prostate biopsy. We hypothesized that men negative for circulating prostate cells have a small risk of clinically significant prostate cancer and thus may be conservatively observed. Men positive for circulating prostate cells should undergo biopsy to confirm prostate cancer. MATERIALS AND METHODS: Consecutive men with a continued suspicion of prostate cancer underwent 12 core TRUS prostate biopsy; age, total serum PSA and percentage free PSA and Chun nomagram scores were registered. Immediately before biopsy an 8ml blood simple was taken to detect primary mCPCs. Mononuclear cells were obtained by differential gel centrifugation and identified using double immunostaining with anti-PSA and anti-P504S. Biopsies were classifed as cancer/no cancer, mCPC detecton test as negative/positive and the total number of cells/8ml registered. Areas under the curve (AUC) for percentage free PSA, Chun score and CPCs were calculated and compared. Diagnostic yields were calculated with reference to the number of possible biopsies that could be avoided and the number of clinically significant cancers that would be missed. RESULTS: A total of 164 men underwent a second biopsy; 41 (25%) had cancer; the AUCs were 0.65 for free PSA, 0.76 for the Chun score and 0.87 for CPC detection, the last having a significantly superior prediction value (p=0.01). Using cut off values of free PSA <10%, Chun score >50% and >=1 CPC detected, CPC detection had a higher diagnostic yield. Some 4/41 cancers complied with the criteria for active surveillance, free PSA and the Chun score missed a higher number of significant cancers when compared with CPC detection. CONCLUSIONS: Primary CPC detection outperformed the use of free PSA and the Chun nomagram in predicting clinically significant prostate cancer at repeat prostate biopsy. PMID- 27356716 TI - Development of a Health Education Modification Program Regarding Liver Flukes and Cholangiocarcinoma in High Risk Areas of Nakhon Ratchasima Province Using Self Efficacy and Motivation Theory. AB - A quasi-experimental study was conducted to develop a health education modification program based on self-efficacy and motivation regarding liver flukes and cholangiocarcinoma development in Keang Sanam Nang district, Nakhon Ratchasima province, Thailand. A total of 36 individuals were invited to participate in the program and were screened for population at risk of liver fluke infection and cholangiocarcinoma using SUT-OV-001 and SUT-CCA-001. Development of health education modification program regarding liver fluke and cholangiocarcinoma prevention included 3 steps: (1) preparation, (2) health education program, and (3) follow-up and evaluation. The study was implemented for 10 weeks. Pre-and-post-test knowledge was measured with questionnaires, Kuder Richardson-20: KR-20 = 0.718,and Cronbach's Alpha Coefficient = 0.724 and 0.716 for perception and outcome expectation questionnaires. Paired and independent t tests were applied for data analysis. The majority of the participants were female (55.6%), aged between <=50 and 60 years old (36.1%), married (86.1%), education level of primary school (63.9%), agricultural occupation (80.6%), and income <4,000 Baht (44.4%). The results revealed that after the health education program, the experimental group had a mean score of knowledge, perception, and outcome expectation regarding liver fluke and cholangiocarcinoma prevention significantly higher than before participation and in the control group. In conclusion, this successful health education modification program for liver fluke and cholangiocarcinoma, therefore may useful for further work behavior modification in other epidemic areas. PMID- 27356717 TI - Metastasis Risk Reduction Related with Beta-Blocker Treatment in Mexican Women with Breast Cancer. AB - BACKGROUND: Breast Cancer (BCa) is the most common malignant tumour in Mexican women. In BCa, several studies have linked beta2-adrenergic receptor activation with increased tumour growth and progression as related with Epinephrine NorEpinephrine (E-NE) stimulation. The aim of this study was to describe Beta Blocker (BB) treatment related with reduction of the risk of metastasis in Mexican patients with BCa. MATERIALS AND METHODS: We collected data of 120 patients seen at the High-Specialty Naval General Hospital in Mexico City (HOSGENAES), all of these with a histopathological diagnosis of BCa. Four groups of patients were divided as follows: without Systemic Arterial Hypertension (SAH); with SAH treatment with non-selective BB; with SAH treatment with selective BB, and with SAH treatment with other antihypertensive drugs. Chi square, Mantel- Haenszel, Student t, and ANOVA tests were performed for data analysis. RESULTS: On average, patients were 54.8+/-11.8 years of age. Risk factors such as smoking and consuming alcohol exhibited a frequency of 33 and 36.5% respectively. Clinical stages III- IV were found in 50% of patients, while, 30% of patients had arterial hypertension (n=29 and N=96, respectively) and 17.5% used BB. One hundred percent of patients with arterial hypertension treated with BB for beta1 - and beta2 -adrenergic-receptors did not present metastasis globally, but patients treated with beta1 BB presented 30% of metastasis while patients treated with no BB or without SAH had around 70% of metastasis. CONCLUSIONS: In Mexican patients with BCa and SAH treated with non-selective (beta1- and beta2-adrenergic receptors) BB, a decrease in the risk for metastasis was observed at the time of diagnosis. PMID- 27356718 TI - Possible Epithelial Ovarian Cancer Association with HPV18 or HPV33 Infection. AB - The present study was conducted to investigate the prevalence of HPV infection in epithelial ovarian cancer (EOC) in Hunan province. DNA samples were collected from paraffin embedded ovarian tissue from 322 patients with EOC, 99 with ovarian benign tumors and 199 normal persons. The polymerase chain reaction and direct sequencing were used to identify the HPV types in the samples. The relationship between the infection of human papillomavirus (HPV) and the epithelial ovarian carcinoma (EOC) was investigated combined with clinical data. The prevalence of HPV18 and HPV33 in EOC group and benign group was higher than in the normal group. HPV18 and HPV33 may play a role in the development of both EOC and ovarian benign tumor and may participate in the development of EOC with traditional risk factors, family history and abortion, possibly exerting synergistic effects.. PMID- 27356719 TI - Knowledge of Cervical Cancer Screening among Health Care Workers Providing Services Across Different Socio-economic Regions of China. AB - BACKGROUND: China carries a heavy burden of cervical cancer (CC) and substantial disparities exist across regions within the country. In order to reduce regional disparities in CC, the government of China launched the National Cervical Cancer Screening Program in Rural Areas (NCCSPRA) in 2009. Critical to the success of the program are the health care workers who play a pivotal role in preventing and managing CC by encouraging and motivating women to use screening services and by providing identification and treatment services. This study aimed to assess cervical cancer knowledge among these health care workers at the county level in maternal and child health (MCH) hospitals across different socio-economic regions of China. MATERIALS AND METHODS: A cross-sectional survey was conducted and self administered questionnaires were sent to all health care workers (a total of 66) providing cervical cancer screening services in 6 county level MCH hospitals in Liaoning, Hubei and Shaanxi provinces, representing eastern, central and western regions of China; 64 (97.0%, 64/66) of the workers responded. ANOVA and Chi square test were used to compare the knowledge rate and scores in subgroups. RESULTS: The knowledge level of the respondents was generally low. The overall combined knowledge rate was 46.9%. The knowledge rates for risk factors, prevention, clinical symptoms, screening and diagnostic tests and understanding of positive results were 31.3%, 37.5%, 18.1%, 56.3% and 84.4%, respectively. Statistically significant differences in scores or rates of CC knowledge were seen across the different regions. The total and sectional scores in the less developed regions were statistically significantly lower than in the other regions. CONCLUSIONS: The majority of the health care workers who provide CC screening service in NCCSPRA at county level MCH hospitals do not have adequately equipped with knowledge about CC. Given the importance of knowledge to the program's success in reducing CC burden in rural women in China, efforts are needed to improve the knowledge of health care workers, especially in less developed regions. PMID- 27356720 TI - Opisthorchis viverrini Infection Among People in the Border Areas of Three Provinces, Northeast of Thailand. AB - Opisthorchis viverrini is still a serious problem in Northeastern and Northern Thailand. Active surveillance is required to determine updated data for further prevention and control planning. Therefore, this study aimed to examine the prevalence and risk factors for O. viverrini in three provinces, Northeastern Thailand. A cross- sectional survey was conducted during October 2015 to March 2016 at Kaeng Sanam Nang district of Nakhon Ratchasima province, Waeng Noi district of Khon Kaen province, and Khon Sawan district of Chaiyaphum province, Thailand. Stool samples were examined by using a modified Kato-Katz Thick smear technique. From a total of 978 participants screened, O. viverrini infection was found in 1.74%, the majority opf positive cases being male (6.62%), age group 51 60 years old (4.21%), educated at primary school (8.43%), occupied with agriculture (9.62%),having an income <4,000 baht per month (4.82%), and living in Khon Sawan district (8.43%). Participants had a high knowledge level (42.43%), good attitude level (34.76%), and fair level (38.04%). The present study indicates the O. viverrini infection rate is low, but elderly males with primary school education involved in agriculture are still frequently effected particularly in Khon Sawan district. Therefore, this risk group requires behavior modification and continued monitoring. PMID- 27356721 TI - Reduced Ovarian Cancer Incidence in Women Exposed to Low Dose Ionizing Background Radiation or Radiation to the Ovaries after Treatment for Breast Cancer or Rectosigmoid Cancer. AB - BACKGROUND: High dose ionizing radiation can induce ovarian cancer, but the effect of low dose radiation on the development of ovarian cancer has not been extensively studied. We evaluated the effect of low dose radiation and total background radiation, and the radiation delivered to the ovaries during the treatment of rectosigmoid cancer and breast cancer on ovarian cancer incidence. MATERIALS AND METHODS: Background radiation measurements are from Assessment of Variations in Radiation Exposure in the United States, 2011. Ovarian cancer incidence data are from the Centers for Disease Control and Prevention. Standardized incidence ratios (SIR) of ovarian cancer following breast cancer and rectosigmoid cancer are from Surveillance, Epidemiology, and End Results (SEER) data. Obesity data by US state are from the Centers for Disease Control and Prevention. Mean ages of US state populations are from the United States Census Bureau. RESULTS: We calculated standardized incidence ratios (SIR) from Surveillance, Epidemiology, and End Results (SEER) data, which reveal that in 194,042 cases of breast cancer treated with beam radiation, there were 796 cases of ovarian cancer by 120+ months of treatment (0.41%); in 283, 875 cases of breast cancer not treated with radiation, there were 1,531 cases of ovarian cancer by 120+ months (0.54%). The difference in ovarian cancer incidence in the two groups was significant (<0.001, two tailed Fisher exact test). The small dose of scattered ovarian radiation (about 3.09 cGy) from beam radiation to the breast appears to have reduced the risk of ovarian cancer by 24%. In 13,099 cases of rectal or rectosigmoid junction cancer treated with beam radiation in the SEER data, there were 20 cases of ovarian cancer by 120+ months of treatment (0.15%). In 33,305 cases of rectal or rectosigmoid junction cancer not treated with radiation, there were 91 cases of ovarian cancer by 120+ months (0.27%). The difference in ovarian cancer incidence in the two groups was significant (p = 0.017, two tailed Fisher exact test). In other words, the beam radiation to rectum and rectosigmoid that also reached the ovaries reduced the risk of ovarian cancer by 44%. In addition, there was a significant inverse relationship between ovarian cancer in white women and radon background radiation (r = - 0.465. p = 0.002) and total background radiation (r = -0.456, p = 0.002). Because increasing age and obesity are risk factors for ovarian cancer, multivariate linear regression was performed. The inverse relationship between ovarian cancer incidence and radon background was significant (beta = - 0.463, p = 0.002) but unrelated to age (beta = - 0.080, p = 0.570) or obesity (beta = - 0.180, p = 0.208). CONCLUSIONS: The reduction of ovarian cancer risk following low dose radiation may be the result of radiation hormesis. Hormesis is a favorable biological response to low toxin exposure. A pollutant or toxin demonstrating hormesis has the opposite effect in small doses as in large doses. In the case of radiation, large doses are carcinogenic. However, lower overall cancer rates are found in U.S. states with high impact radiation. Moreover, there is reduced lung cancer incidence in high radiation background US states where nuclear weapons testing was done. Women at increased risk of ovarian cancer have two choices. They may be closely followed (surveillance) or undergo immediate prophylactic bilateral salpingo-oophorectomy. However, the efficacy of surveillance is questionable. Bilateral salpingo-oophorectomy is considered preferable, although it carries the risk of surgical complications. The data analysis above suggests that low-dose pelvic irradiation might be a good third choice to reduce ovarian cancer risk. Further studies would be worthwhile to establish the lowest optimum radiation dose. PMID- 27356722 TI - Prioritizing the Preferences of Iranian Cancer Patients Regarding Acquisition of Health Information: Strategy for Patient Education. AB - Recognizing cancer patients' preferences to obtain health information can help improve and reform the methods of communicating and providing proper services and consequently lead to effective patient education. The present cross-sectional study to prioritize the preferences of cancer patients regarding the acquisition of health informationwas conducted on cancer patients referred to hospitals affiliated to Semnan University of Medical Sciences in 2015. An anonymous self administered questionnaire was developed. In the field of side effects of medications, 50 (46.7%) reported knowing about weight change, in the area of achieving relative health, 62(57.9%) announced awareness about diet, and 45 (42.1%) reported physical complications as a first regarding information needs. In the area of obtaining information, 50 (46.7%) tended to take their information through means outside of the hospital setting. These results can help with design of clinical information systems, as they inform the most relevant and useful coverage designed for cancer patients. Providing useful information through healthcare providers, the media and clinical information systems can act as a major source of social support for cancer patients. PMID- 27356723 TI - Circulating DNA in Egyptian Women with Breast Cancer. AB - The commonest cancer in Egyptian females occurs in the breast cfDNA is a non invasive marker for tumor detetion and prognostic assessment in many types of cancer including breast cancer. This study aimed to assess the role of cfDNA and its fragmentation pattern in breast cancer prognosis and treatment response. Forty female patients with malignant breast tumors and a comparable group of healthy blood donors were enrolled prospectively. cfDNA levels and fragmentation patterns were investigated after cfDNA extraction, gel electrophoresis and gel analysis. The percentage of breast cancer patients positive for cfDNA (92.5%) was significantly higher than that of controls (55%). Also, mean concentration of cfDNA was significantly higher than in the control group (<0.05). Most Her-2 positive patients had long cfDNA fragments, this being significant as compared to Her-2 negative patients (<0.05). Metastasis was also positively linked to significantly higher cfDNA (<0.05) and the mean cfDNA integrity index was significantly higher in non-responders compared to treatment responders (<0.05). In conclusion, both qualitative and quantitative aspects of cfDNA and its different fragments in breast cancer patients could be related to prognosis, metastasis and treatment response. Long cfDNA fragments could be particularly useful for prediction purposes. PMID- 27356724 TI - Eight Year Survival Analysis of Patients with Triple Negative Breast Cancer in India. AB - BACKGROUND: Triple-negative breast cancer (TNBC) often presents as an interval cancer with short survival upon metastasis and thus represents an important clinical challenge. The present study investigated the clinicopathologic characteristics and long term survival outcome of early and locally advanced TNBC. MATERIALS AND METHODS: Medical records were reviewed retrospectively for 148 consecutive confirmed cases of TNBC treated in a single unit at our centre. Demographic profile, tumor type, histopathology details, treatment and follow-up information was recorded and immunohistochemistry was performed. RESULTS: Age group >50 years was associated with tumors of clinical stage 3 (53.8%), pathological stage 3 (46.2%), pathological grade 3 (45.7%), presence of extracapsular extension (ECE, 48.5%) and lymphovascular invasion (LVI, 64.9%). Locally advanced breast cancers (LABCs) were characterized by pathological stage 3 (96.2%), presence of ECE (100%) and absence of LVI (46.7%) as compared to early breast cancers (EBCs) which had higher incidence of lower stage tumors (100%), absence of ECE (82%) and presence of LVI (91.9%; p-value <0.001. Better relapse free survival was observed in patients with no axillary involvement (69%; p-value <0.001) and absence of ECE (64%; p-value <0.001). Improved overall survival was seen in patients with EBC (90%; p-value 0.008), clear axilla (86%; p-value <0.001), absence of ECE (87%; p-value <0.001) and negative lymph nodes (90%; p value 0.006). CONCLUSIONS: TNBCs are aggressive tumors which show poor long term survival. Patients with TNBC benefit from chemotherapy, thus better and less toxic treatment options are needed. Identification of newer targets and development of targeted therapies are the need of the hour. PMID- 27356725 TI - Genetic Abnormalities in Oral Leukoplakia and Oral Cancer Progression. AB - BACKGROUND: The cancer progression of oral leukoplakia is an important watchpoint in the follow-up observation of the patients. However, potential malignancies of oral leukoplakia cannot be estimated by histopathologic assessment alone. We evaluated genetic abnormalities at the level of copy number variation (CNV) to investigate the risk for developing cancer in oral leukoplakias. MATERIALS AND METHODS: The current study used 27 oral leukoplakias with histological evidence of dysplasia. The first group (progressing dysplasia) consisted of 7 oral lesions from patients with later progression to cancer at the same site. The other group (non- progressing dysplasia) consisted of 20 lesions from patients with no occurrence of oral cancer and longitudinal follow up (>7 years). We extracted DNA from Formalin-Fixed Paraffin-Embedded (FFPE) samples and examined chromosomal loci and frequencies of CNVs using Taqman copy number assays. RESULTS: CNV frequently occurred at 3p, 9p, and 13q loci in progressing dysplasia. Our results also indicate that CNV at multiple loci-in contrast to single locus occurrences is characteristic of progressing dysplasia. CONCLUSIONS: This study suggests that genetic abnormalities of the true precancer demonstrate the progression risk which cannot be delineated by current histopathologic diagnosis. PMID- 27356726 TI - Evaluating Direct Costs of Gastric Cancer Treatment in Iran - Case Study in Kerman City in 2015. AB - BACKGROUND: Gastrointestinal cancers are common malignancies associated with high mortality rates. Health- care systems are always faced with high costs of treatment of gastrointestinal cancers including stomach cancer. Identification and prioritization of these costs can help determine economic burden and then improve of health planning by policy-makers. This study was performed in 2015 in Kerman City aimed at estimating the direct hospital costs for patients with gastric cancer. MATERIALS AND METHODS: In this cross-sectional study, the medical records of 160 patients with stomach cancer admitted from 2011 to 2014 to Shafa Hospital were examined, the current stage of the disease and the patients' health status were identified, and the direct costs related to the type of treatment in the public and private sectors were calculated. SPSS-19 was used for statistical analysis of the data. RESULTS: Of the patients studied, 103 (65%) were men and 57 (35%) were women. The mean age of patients was 65 years. Distribution into four stages of the disease was 5%, 20%, 30%, and 45%, respectively. Direct costs in four stages of the disease were calculated as 2191.07, 2642.93, 2877, and 2674.07 USD (63,045,879, 76,047,934, 82,783,019, and 76,943,800 IRR), respectively. The highest percentage of costs was related to surgery in Stage I and to medication in Stages II, III, and IV. According to the results of direct costs of treatment for stomach cancer in Kerman, the mean total cost of treating a patient in the public sector was estimated at 74,705,158 IRR, of which averages of 60,141,384 IRR and 14,563,774 IRR were the shares of insurance and patients, respectively. CONCLUSIONS: The high prevalence and diagnosis of disease in old age and at advanced stages of disease impose great costs on the patients and the health system. Early diagnosis through screening and selecting an appropriate treatment method might largely ameliorate the economic burden of the disease. PMID- 27356727 TI - DNMT3B -149 C>T and -579 G>T Polymorphisms and Risk of Gastric and Colorectal Cancer: a Meta-analysis. AB - BACKGROUND: Numerous studies have investigated associations of DNA methyltransferase (DNMT) -149 C>T and -579 G>T polymorphisms with gastric cancer (GC) and colorectal cancer (CRC) susceptibility; however, the findings are inconsistent prompting the present meta-analysis. MATERIALS AND METHODS: Related studies were identified from PubMed, Google scholar, and SID until 10 October 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. RESULTS: Eleven studies were included based on the search criteria for CRC and GC related to the DNMT3B 149 C>T (3,353 cases and 4,936 controls) and DNMT3B 579 G>T (1,387 cases and 2,064 controls) polymorphisms. There was no significant association overall between DNMT3B -149 and 579 polymorphisms and the risk of cancer. In the stratified analysis by cancer type, DNMT3B 579G>T polymorphism was associated with the risk of CRC and GC. While the DNMT3B -149C/T polymorphism was related with a significantly increased risk of CRC in two tested models, dominant (GG+GT vs. TT: OR 0.51, 95 % CI 0.38-0.69; P = 0.00, Pheterogeneity=0.69, I2= 0 %) and heterozygote (GT vs. TT: OR 0.50, 95 % CI 0.37-0.69; P=0.00, Pheterogeneity=0.41, I2= 0 %), no evidence of any association with GC risk was observed as in the pooled analyses. CONCLUSIONS: More studies are needed to assess associations of DNMT3B -149C/T and DNMT3B 579G>T polymorphisms with cancer in different ethnicities with large population sizes to generate comprehensive conclusions. PMID- 27356728 TI - Auto-Coding of Cancer Registry Data in China. AB - The significance, difficulty and strategy of coding cancer data according to international coding standards are discussed, and the concept, methods and realization of cancer data automatic coding in cancer registries in China are introduced in the paper. Coding cancer data automatically with software could not only reduce the time, manpower and workload, while improving the accuracy and efficiency of cancer data coding, but also enhance the validity of cancer registration and the value of cancer registry data, which is of great significance. PMID- 27356729 TI - A case of complex partial seizure with reversible MRI abnormalities in the elderly. AB - A 79-year-old woman was admitted to our hospital because of prolonged impaired consciousness and right hemiparesis. She was treated for acute cerebral infarction because her brain magnetic resonance imaging showed extensive cortical lesions similar to acute infarction in diffusion weighted image, fluid attenuated inversion recovery, and T2 weighted images. On the fifth day, she had a focal seizure on the right side. A new lesion during imaging and electroencephalogram abnormality were observed at that time. After the antiepileptic drug treatment was started, her right hemiparesis considered as ictal paresis, confusion, and the magnetic resonance imaging findings gradually improved. There was also an old, irreversible lesion in the left hippocampus, which was considered as the focus of her complex partial seizure. In the elderly, the post-ictal period of confusion, which occurs with complex partial seizure, may be prolonged. In our case, improvement of hemiparesis and confusion occurred after about 2 weeks. PMID- 27356730 TI - Analysis of resting salivation rate in patients with amyotrophic lateral sclerosis using tracheostomy invasive ventilation. AB - Patients with amyotrophic lateral sclerosis (ALS) often suffer from salivation problems such as drooling and dry mouth. We examined resting salivation rate cross-sectionally in 66 advanced ALS patients with tracheostomy invasive ventilation using a cotton roll method, and investigated clinical factors associated with salivation rate. Resting salivation rate in the patients was well preserved (median value 0.6 g/min), and was significantly more increased in patients with impairment of jaw movement (P = 0.007) or mouth opening (P = 0.003) than in patients with less impairment, and in patients with the mouth being constantly open >= 10 mm in rostrocaudal length than in patients with < 10 mm. These data indicate that salivation rate was increased with progression of dysfunction of voluntary jaw movement. Appropriate oral care is required in advanced ALS patients to maintain their oral hygiene and to avoid penetration of saliva into the airway. PMID- 27356731 TI - A case of slowly progressive anti-Yo-associated paraneoplastic cerebellar degeneration successfully treated with antitumor and immunotherapy. AB - We report a case of slowly progressive anti-Yo-associated paraneoplastic cerebellar degeneration (PCD) with breast cancer in a 54-year-old woman. The symptoms of limb and truncal ataxia, and dysarthria gradually progressed during the course of 1 year, and the modified Rankin scale (mRS) score was 2. A mastectomy with sentinel lymph node resection was performed for the breast cancer. No malignant cells were found on histopathological examination of the lymph node. Combination chemotherapy with adriamycin and cyclophosphamide (AC) prevented neurologic deterioration. However, subsequent treatment with trastuzumab and paclitaxel did not prevent progression of the symptoms (mRS score 3). Brain magnetic resonance imaging showed atrophy of the cerebellar hemispheres without brain stem atrophy. Anti-Yo antibody was detected in the serum, which led to a diagnosis of anti-Yo-associated PCD. We resected an enlarged axillary lymph node, which was found on computed tomography. The histopathological analysis of the lymph node revealed foreign body granuloma, which suggested an association with necrotic malignant tissue. Following additional tegafur-uracil therapy and two courses of intravenous immunoglobulin (IVIg), the cerebellar signs and symptoms gradually improved (mRS score 2). The clinical course shows that PCD can present as a slowly progressive cerebellar symptom. We propose an active treatment for anti-Yo-associated PCD consisting of tumor resection, combined chemotherapy, and IVIg. PMID- 27356732 TI - Progressive multifocal leukoencephalopathy with bilateral middle cerebellar peduncle lesions confirmed by repeated CSF-JC virus tests and coexistence of JC virus granule cell neuronopathy. Report of a case. AB - A 65 year-old woman with small lymphocytic leukemia presented with subacute cerebellar ataxia. Six months after rituximab chemotherapy, a cranial MRI revealed lesions in the bilateral middle cerebellar peduncles. Both cerebrospinal fluid (CSF) JC virus (JCV)-DNA PCR test on three occasions and brain biopsy were negative. CSF tests were repeated. The fourth test performed 6 months after the onset showed positive JCV-DNA, and a definite diagnosis of progressive multifocal leukoencephalopathy (PML) was made. Neuroimaging of cerebellar atrophy was considered to be coexistence of granule cell neuronopathy. Medication with mirtazapine and mefloquine was temporarily effective for several months. Little are known solitary bilateral MRI lesions of the middle cerebellar peduncle in PML. JCV-PCR test of CSF may be negative at an earlier stage of PML. Repeated CSF tests should be essential to confirming the diagnosis in such cases. PMID- 27356733 TI - An autopsy case of superficial siderosis of the central nervous system accompanied by anterior sacral polycystic meningocele in neurofibromatosis type 1. AB - A 74-year-old female patient, who was diagnosed with neurofibromatosis type 1 (NF1) at the age of 40, was admitted with complaints of flickering vision and gait disturbance for the last 2 years. On admission, neurological examination revealed mild bilateral hearing loss and ataxia in the limb and trunk. Laboratory tests revealed anti-hepatitis C virus (HCV) antibody positivity and elevated HCV RNA by real-time polymerase chain reaction. The cerebrospinal fluid examination revealed a slightly yellowish appearance with elevated total protein levels. Gradient echo T2*-weighted brain magnetic resonance imaging (MRI) demonstrated a rim of hypointense lesions surrounding the surface of the cerebellum, brainstem, frontal and temporal lobes, and thalamus, which was considered as hemosiderin depositions. From these MRI findings, she was diagnosed as having superficial siderosis of the central nervous system. Cerebral angiography revealed an aneurysm-like dilatation at the bifurcation of the right internal carotid posterior communicating artery. (99m)Tc-ethyl cysteinate dimer single-photon emission computed tomography revealed hypoperfusion in the bilateral frontal and temporal lobes. Pelvic plain X-ray, pelvic computed tomography, and lumbosacral MRI revealed a sacral defect and an anterior sacral polycystic meningocele communicating with the spinal subarachnoid space. The patient's symptoms gradually worsened, and she died of septic shock because of pyelonephritis at the age of 77. An autopsy was performed; on pathological examination, we did not observe any findings associated with rupture of the aneurysm-like dilatation in the bifurcation of the right internal carotid-posterior communicating artery and cerebral amyloid angiopathy. Because duropathies-a new neurological disease concept-have been implicated as a cause of bleeding in the superficial siderosis, the anterior sacral polycystic meningocele, a type of duropathies, was presumed to be the most probable bleeding source of the superficial siderosis in this patient. Bleeding from the meningocele might result from the vulnerability of vessel walls in NF1. PMID- 27356734 TI - A case of hemifacial paresis in a patient with Lyme neuroborreliosis treated with antibiotics in whom Borrelia meningitis developed. AB - A 38-year-old man visited our hospital because of hemifacial paresis that developed 2 months after being bit by a tick. We diagnosed idiopathic peripheral facial palsy and gave the patient oral prednisolone and valacyclovir. Although the symptoms completely resolved in about 2 weeks, there was a risk of Lyme neuroborreliosis. The patient therefore received doxycycline (100 mg twice daily) and amoxicillin (1,000 mg 3 times daily) for 14 days. Two months later, he had symptoms of meningitis such as headache and fever accompanied by lymphocytic cerebrospinal fluid pleocytosis. Viral meningitis was diagnosed and treated with parenteral acyclovir. The symptoms of meningitis improved. Tests for serum IgG antibodies against borrelia were positive. We gave the patient a diagnosis of Lyme neuroborreliosis. The patient received intravenous ceftriaxone and had no relapse. It is a rare for meningitis to develop in a patient with cranial neuropathy who received doxycycline. Lyme neuroborreliosis is a rare disease in Japan. Care should therefore be exercised in the diagnosis of Lyme neuroborreliosis and evaluation of the response to treatment. PMID- 27356735 TI - A case of vitamin B12 deficiency with involuntary movements and bilateral basal ganglia lesions. AB - An 86-year-old woman with a one-year history of dementia was admitted to our hospital complaining of loss of appetite, hallucinations, and disturbance of consciousness. She gradually presented with chorea-like involuntary movements of the extremities. Diffusion-weighted magnetic resonance imaging (MRI) showed bilateral symmetrical hyperintense signals in the basal ganglia. The serum vitamin B12 level was below the lower detection limit of 50 pg/ml. The homocysteine level was markedly elevated at 115.8 nmol/ml. Anti-intrinsic factor and anti-parietal cell antibody tests were positive. Gastrointestinal endoscopy revealed atrophic gastritis. The patient was diagnosed with encephalopathy due to vitamin B12 deficiency caused by pernicious anemia. Involuntary movements and MRI abnormalities improved with parenteral vitamin B12 supplementation. Bilateral basal ganglia lesions are rare manifestations of adult vitamin B12 deficiency. The present case is considered valuable in identifying the pathophysiology of involuntary movement due to vitamin B12 deficiency. PMID- 27356736 TI - Periodic synchronous discharge occurred in an elderly with acute valacyclovir associated encephalopathy. AB - An 81-year-old woman suffering from sarcoidosis, chronic renal failure caused by hypertention was treated by valacyclovir 500 mg/day, for the diagnosis of herpes zoster of her right back. Her consciousness gradually became worse, and 3 days after taking the drug, she was sent to the emergency department of the hospital. Her conscious level was E2V2M5 (Glasgow Coma Scale) and myoclonus especially in her lower extremities occurred. Head CT and MRI show no obvious, acute abnormal findings other than chronic ischemic lesions, while an electroencephalogram (EEG) shows periodic synchronous discharges (PSDs) and disorganized background activity. Based on these findings, she was diagnosed as valacyclovir-associated acute encephalopathy. After conservative therapy of maintenance hemodialysis, her consciousness gradually improved, and PSDs disappeared accordingly and background activity of EEG became improved. In this case report, we presented valacyclovir associated neurotoxicity with PSDs in EEG as potentially a surrogate marker. We should be cautious to use valaciclovir which may cause drug-induced encephalopathy especially in elderly or patients with renal failure even though the dose was adjusted in advance. PMID- 27356737 TI - Expanding concept of clinical conditions and symptoms in multiple system atrophy. AB - Multiple system atrophy (MSA) is an adult-onset, progressive neurodegenerative disorder. MSA patients show various phenotypes during the course of their illness including parkinsonism, cerebellar ataxia, autonomic failure, and pyramidal signs. MSA is classified into the parkinsonian (MSA-P) or cerebellar (MSA-C) variant depending on the clinical motor phenotype at presentation. MSA-P and MSA C are predominant in Western countries and Japan, respectively. The mean age at onset is 55 to 60 years. Prognosis ranges from 6 to 10 years, but some cases survive for more than 15 years. Early and severe autonomic failure is a poor prognostic factor. MSA patients sometimes present with isolated autonomic failure or motor symptoms/signs, and the median duration from onset to the concomitant appearance of motor and autonomic symptoms was approximately 2 years in our previous study. As the presence of the combination of motor and autonomic symptoms is essential for the current diagnostic criteria, early diagnosis is difficult when patients present with isolated autonomic failure or motor symptoms/signs. We experienced MSA patients who died before presentation of the motor symptoms/signs diagnostic for MSA (i.e., premotor MSA). Detection of the nature of autonomic failure consistent with MSA and identification of the dysfunctional anatomical sites may increase the probability of a diagnosis of premotor MSA. Dementia is another problem in MSA. Although dementia had been thought to be rare in MSA, frontal lobe dysfunction is observed frequently during the early course of the illness. Magnetic resonance imaging can show progressive cerebral atrophy in longstanding cases. More recently, MSA patients presenting with frontotemporal dementia preceding the presence of motor and autonomic manifestations diagnostic of MSA have been reported. Novel diagnostic criteria based on an expanding concept of the clinical conditions and symptoms of MSA will be needed for the development of disease-modifying therapies and better management. PMID- 27356738 TI - A metal-catalyzed enyne-cyclization step for the synthesis of bi- and tricyclic scaffolds amenable to molecular library production. AB - A facile metal-catalyzed diversification step for the synthesis of novel bi- and tricyclic scaffolds from enyne substrates is reported in this study. From a single starting material, topologically diverse scaffolds for library synthesis can be generated and decorated in a few steps. The methodology was used to produce a library of 490 compounds within the European Lead Factory (ELF) Consortium. PMID- 27356739 TI - Aurora kinase A revives dormant laryngeal squamous cell carcinoma cells via FAK/PI3K/Akt pathway activation. AB - Revival of dormant tumor cells may be an important tumor metastasis mechanism. We hypothesized that aurora kinase A (AURKA), a cell cycle control kinase, promotes the transition of laryngeal squamous cell carcinoma (LSCC) cells from G0 phase to active division. We therefore investigated whether AURKA could revive dormant tumor cells to promote metastasis. Western blotting revealed that AURKA expression was persistently low in dormant laryngeal cancer Hep2 (D-Hep2) cells and high in non-dormant (T-Hep2) cells. Decreasing AURKA expression in T-Hep2 cells induced dormancy and reduced FAK/PI3K/Akt pathway activity. Increasing AURKA expression in D-Hep2 cells increased FAK/PI3K/Akt pathway activity and enhanced cellular proliferation, migration, invasion and metastasis. In addition, FAK/PI3K/Akt pathway inhibition caused dormancy-like behavior and reduced cellular mobility, migration and invasion. We conclude that AURKA may revive dormant tumor cells via FAK/PI3K/Akt pathway activation, thereby promoting migration and invasion in laryngeal cancer. AURKA/FAK/PI3K/Akt inhibitors may thus represent potential targets for clinical LSCC treatment. PMID- 27356740 TI - CRISPR-dCas9 mediated TET1 targeting for selective DNA demethylation at BRCA1 promoter. AB - DNA hypermethylation at the promoter of tumour-suppressor genes is tightly correlated with their transcriptional repression and recognized as the hallmark of majority of cancers. Epigenetic silencing of tumour suppressor genes impairs their cellular functions and activates a cascade of events driving cell transformation and cancer progression. Here, we examine site-specific and spatiotemporal alteration in DNA methylation at a target region in BRCA1 gene promoter, a model tumour suppressor gene. We have developed a programmable CRISPR Cas9 based demethylase tool containing the deactivated Cas9 (dCas9) fused to the catalytic domain (CD) of Ten-Eleven Translocation (TET) dioxygenase1 (TET1CD). The fusion protein selectively demethylates targeted regions within BRCA1 promoter as directed by the designed single-guide RNAs (sgRNA), leading to the transcriptional up-regulation of the gene. We also noticed the increment in 5 hydroxymethylation content (5-hmC) at the target DNA site undergoing the most profound demethylation. It confirms the catalytic activity of TET1 in TET1-dCas9 fusion proteins-mediated demethylation at these target sequences. The modular design of the fusion constructs presented here allows for the selective substitution of other chromatin or DNA modifying enzymes and for loci-specific targeting to uncover epigenetic regulatory pathways at gene promoters and other selected genomic regions. PMID- 27356741 TI - PD1 blockade enhances cytotoxicity of in vitro expanded natural killer cells towards myeloma cells. AB - Aiming for an adoptive natural killer (NK) cell therapy, we have developed a novel protocol to expand NK cells from peripheral blood. With this protocol using anti-human CD16 antibody and interleukin (IL)-2, NK (CD3-CD56+) cells could be expanded about 4000-fold with over 70% purity during a 21-day culture. The expanded NK (exNK) cells were shown to be highly cytotoxic to multiple myeloma (MM) cells (RPMI8226) at low NK-target cell ratios. Furthermore, NK cells expanded in the presence of a blocking antibody (exNK+PD1-blockage) against programmed cell death protein-1 (PD1), a key counteracting molecule for NK and T cell activity, demonstrated more potent cytolytic activity against the RPMI8226 than the exNK cells without PD1 blocking. In parallel, the exNK cells showed significantly higher expression of NK activation receptors NKG2D, NKp44 and NKp30. In a murine model of MM, transfusion of exNK cells, exNK+PD1-blockage, and exNK plus intratumor injection of anti-PD-L2 antibody (exNK+PD-L2 blockage) all significantly suppressed tumor growth and prolonged survival of the myeloma mice. Importantly, exNK+PD1-blockage presented more efficient therapeutic effects. Our results suggest that the NK cell expansion protocol with PD1 blockade presented in this study has considerable potential for the clinical application of allo- and auto-NK cell-based therapies against malignancies. PMID- 27356742 TI - Thyroid functional parameters and correlative autoantibodies as prognostic factors for differentiated thyroid cancers. AB - To evaluate the effect of preoperative thyroid functional parameters and thyroid autoantibodies on aggressive clinicopathologic features and lymph node metastasis (LNM) of differentiated thyroid cancer patients. Four hundred twenty consecutive patients with initial surgery were enrolled from July 2010 to July 2015. The associations between aggressive clinicopathologic and LNM factors and thyroid functional & autoantibodies parameters were analyzed. Higher levels of TSH, TGAb or TMAb were found in patients with tumor size>=1 cm (all P<0.05), especially when TSH>=2.5 ulU/ml (P=0.03) and TGAb>=1 (P=0.01). Higher levels of TSH and TGAb and lower levels of T3 and T4 were found in patients with capsular invasion (all P<0.05), particularly when TSH>=2.5ulU/ml (P=0.03) and TGAb>=1 (P=0.005). The patients with multifocality had higher TAbs level (TAbs>1). Higher level of TSH was also found in patients with central LNM (P=0.001) and lateral LNM (P=0.002), especially with TSH>=2.5ulU/ml (P=0.003 and P=0.03). TGAb level was also found higher in patients with central LNM (P=0.02) and lateral LNM (P=0.01), especially with TGAb>=1 (P<0.05 and P=0.01). Higher level of TMAb was found in patients with lateral LNM (P<0.05). Moreover, multivariable analysis revealed that only TGAb was an independently predictive factor for primary tumor size>=1cm (P=0.01); and TSH level (P=0.01) and TGAb>=1 (P<0.05) were associated independently with central LNM. Thus, TSH level and TGAb>=1 were significantly independent predictors for central LNM, and might help make the decision of central neck dissection. PMID- 27356743 TI - Significant benefits of adding neoadjuvant chemotherapy before concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a meta analysis of randomized controlled trials. AB - PURPOSE: We did a meta-analysis to compare the efficacy and safety of neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy (CCRT) versus CCRT with or without adjuvant chemotherapy (AC) for patients with locoregionally advanced nasopharyngeal carcinoma based on randomized controlled trials. METHODS: We searched PubMed, Embase, Web of Science, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, and meeting proceedings of major relevant conferences to identify published and unpublished randomized controlled trials. Progression free survival (PFS) was the primary endpoint. RESULTS: This meta-analysis included 9 randomized clinical trials with 2215 patients. NACT followed by CCRT significantly improved PFS (HR=0.68, 95% CI 0.56 - 0.81, P < 0.001) compared versus CCRT with or without AC, and no heterogeneity was observed (I2 = 0.0%, P = 0.975). NACT was associated with a significant improvement in overall survival (HR = 0.64, 95% CI 0.49 - 0.84, P = 0.001; I2 = 0.0%, P = 0.467) and distant failure-free survival (HR = 0.72, 95% CI 0.53 - 0.97, P = 0.031; I2 = 0.0%, P = 0.744). No significant benefit was shown by NACT for locoregional control. NACT with CCRT increased risks of grade 3 - 4 anemia, thrombocytopenia, leukopenia, and fatigue, compared versus CCRT with or without AC. CONCLUSIONS: Our meta analysis confirmed that the addition of NACT to CCRT significantly improved PFS and OS versus CCRT with or without AC for locoregionally advanced nasopharyngeal carcinoma. These results may alter the standard of care - CCRT with or without AC, for locoregionally advanced nasopharyngeal carcinoma. PMID- 27356744 TI - MMP7 interacts with ARF in nucleus to potentiate tumor microenvironments for prostate cancer progression in vivo. AB - ARF couples with TP53 in a canonical signaling pathway to activate cellular senescence for tumor suppressive function under oncogenic insults. However, the mechanisms on aberrant elevation of ARF in cancers are still poorly understood. We previously showed that ARF (p14ARF in human and p19Arf in mouse) elevation correlates with PTEN loss and stabilizes SLUG to reduce cell adhesion in prostate cancer (PCa). Here we report that ARF is essential for MMP7 expression, E Cadherin decrease and the anchorage loss to the extracellular matrix (ECM) in PCa in vitro and in vivo. We found that Mmp7 is aberrantly elevated in cytosol and nucleus of malignant prostate tumors of Pten/Trp53 mutant mice. Interestingly, p19Arf deficiency strikingly decreases Mmp7 levels but increases E-Cadherin in Pten/Trp53/p19Arf mice. ARF knockdown markedly reduces MMP7 in human PCa cells. Conversely, tetracycline-inducible expression of ARF increases MMP7 with a decrease of E-Cadherin in PCa cells. Importantly, MMP7 physically binds ARF to show the co-localization in nucleus. Co-expression of MMP7 and ARF promotes cell migration, and MMP7 knockdown decreases wound healing in PCa cells. Furthermore, MMP7 elevation correlates with ARF expression in advanced human PCa. Our findings reveal for the first time that the crosstalk between ARF and MMP7 in nucleus contributes to ECM network in tumor microenvironments in vivo, implicating a novel therapeutic target for advanced PCa treatment. PMID- 27356745 TI - CCR4 promotes metastasis via ERK/NF-kappaB/MMP13 pathway and acts downstream of TNF-alpha in colorectal cancer. AB - Chemokines and chemokine receptors are causally involved in the metastasis of human malignancies. As a crucial chemokine receptor for mediating immune homeostasis, however, the role of CCR4 in colorectal cancer (CRC) remains unknown. In this study, we found that high expression of CCR4 in CRC tissues was correlated with shorter overall survival and disease free survival. In vitro and in vivo experiments revealed that silencing CCR4 attenuated the invasion and metastasis of CRC cells, whereas ectopic overexpression of CCR4 contributed to the forced metastasis of these cells. We further demonstrated that matrix metalloproteinase 13 (MMP13) played an important role in CCR4-mediated cancer cell invasion, which is up-regulated by ERK/NF-kappaB signaling. Positive correlation between CCR4 and MMP13 expression was also observed in CRC tissues. Moreover, our investigations showed that the level of CCR4 could be induced by TNF-alpha dependent of NF-kappaB activation in CRC cells. CCR4 might be implicated in TNF-alpha-regulated cancer cells metastasis. Combination of CCR4 and TNF-alpha is a more powerful prognostic marker for CRC patients. These findings suggest that CCR4 facilitates metastasis through ERK/NF-kappaB/MMP13 signaling and acts as a downstream target of TNF-alpha. CCR4 inhibition may be a promising therapeutic option for suppressing CRC metastasis. PMID- 27356746 TI - Persistent donor derived Vdelta4 T cell clones may improve survival for recurrent T cell acute lymphoblastic leukemia after HSCT and DLI. AB - The outcome for T-cell acute lymphoblastic leukemia (T-ALL) in relapse after hematopoietic stem cell transplantation (HSCT) is quite poor, while, both donor lymphocytes infusion (DLI) and adoptively infusion of gammadelta T cells in leukemia patients after HSCT have demonstrated good results in prolonging survival time of patients. Here, we reported a T-ALL case who experienced three relapses and received HSCT and DLI with an overall survival (OS) time lasting for more than seven years. Based on our previous identification of a leukemic and reactive clone in this patient, continual gammadelta T cell repertoire monitoring affirmed that the same Vdelta5 leukemic clone existed in most samples from the patient, particularly including a sample taken at the time of the third T-ALL relapse, while it could not be detected in the donor sample. In addition, an identical Vdelta4 monoclonal T cell that proliferated in the recipient for several years was confirmed to come from the donor graft, and its expression level significantly increased in third leukemia recurrence. These results indicate that clonally expanded Vdelta4 T cells may represent a reconstituted gammadelta T cell repertoire after HSCT, which also hints to a relatively better outcome for this case. Based on this case study, we recommend DLI should be as a treatment strategy for patients who achieve CR or relapse from HSCT. Moreover, dynamically monitoring the TCR repertoire in patients who receive HSCT will benefit in supervising of malignant clone evolution and residue, identifying T cell clones mediate anti-infection, GvHD or GvL. PMID- 27356747 TI - IL-17 down-regulates the immunosuppressive capacity of olfactory ecto-mesenchymal stem cells in murine collagen-induced arthritis. AB - Olfactory ecto-mesenchymal stem cells (OE-MSCs) are a population of cells which has been recognized as a new resident stem cell type in the olfactory lamina propria. OE-MSCs have been shown to exert their immunosuppressive capacity by modulating T cell responses, including up-regulation of regulatory T cells (Tregs) and down-regulation of Th1/Th17 cells. As an inflammatory cytokine, IL-17 plays a critical role in orchestrating the inflammatory response during the development of collagen-induced arthritis (CIA). However, it is unclear whether the increased level of IL-17 may affect the immunosuppressive function of OE-MSCs under inflammatory condition. In this study, we found that IL-17 could significantly reduce the suppressive capacity of OE-MSCs on CD4+ T cells and down regulate the suppressive factors produced by OE-MSCs. Notably, IL-17 treatment abolished the capacity of OE-MSCs in inducing Treg expansion. In addition, knockdown of IL-17R in OE-MSCs significantly enhanced their therapeutic effect in ameliorating CIA upon adoptive transfer. Moreover, IL-17R knockdown-OE-MSCs could efficiently induce Tregs expansion and reduce Th1 and Th17 responses. Taken together, all these data suggest that IL-17R knockdown in OE-MSCs may provide a novel strategy in maintaining their immunosuppressive properties for the treatment of autoimmune diseases. PMID- 27356748 TI - Metformin and cancer: Quo vadis et cui bono? AB - How many lives have already been saved by the anti-cancer drug metformin? Inadvertently perhaps, among the millions of type 2 diabetics with occult or known cancers and who have been prescribed metformin since the 1950s, thousands may have benefited from the anticancer properties of this first-line pharmacotherapy. Quo vadis? Now, researchers aim to move metformin from a non targeted stage of cancer therapy that has been mostly developed retrospectively and empirically into a targeted therapy by following a biological rationale and a predefined mechanism of action. But, who might benefit from metformin? Cui bono? Because metformin is on the leading edge of a new generation of cancer metabolism targeted therapies, perhaps it is the right time to provide solutions to the challenges that metformin and other onco-biguanides will face in the coming years before becoming incorporated into the therapeutic armamentarium against cancer. PMID- 27356749 TI - Baicalein is an available anti-atherosclerotic compound through modulation of nitric oxide-related mechanism under oxLDL exposure. AB - OxLDL facilitate reactive oxygen species (ROS) formation and up-regulation of the executioner caspase-3 via the mitochondrial apoptotic pathway involves several critical steps in human endothelial cells. Previous studies reported that oxLDL facilitated endothelial oxidative stress is associated with impairment of eNOS and up-regulation of inducible nitric oxide synthase (iNOS). Baicalein is the most abundant component that has anti-HIV, anti-tumor, anti-oxidant and free radical scavenging functions. In this present study, we shown that baicalein hinibits oxLDL-caused endothelial dysfunction through suppression of endothelial inflammation and oxidative stress that causes to cellular apoptosis. Specifically, baicalein reduces the elevation of ROS concentration, which subsequently inhibits the oxLDL-decreased expression of anti-oxidant enzymes, enriches the bioavailability of NO, stabilizes the mitochondrial membrane, thereby inhibiting the discharge of cytochrome c from mitochondria, a molecule required for the activation of the pro-apoptotic protein caspase 3. However, inhibition of eNOS impairs the anti-apoptotic and anti-inflammatory effects of baicalein. These results provide new insight into the possible molecular mechanisms by which baicalein protects against atherogenesis by NO-related pathways. PMID- 27356750 TI - Identification of IFN-gamma-producing T cells as the main mediators of the side effects associated to mouse interleukin-15 sustained exposure. AB - : Interleukin-15 (IL-15) is a cell growth-factor that regulates lymphocyte function and homeostasis. Its strong immunostimulatory activity coupled with an apparent lack of toxicity makes IL-15 an exciting candidate for cancer therapy, somehow limited by its short half-life in circulation. To increase IL-15 bioavailability we constructed a recombinant adeno-associated vector expressing murine IL-15 (AAV-mIL15) in the liver. Mice injected with AAV-mIL15 showed sustained and vector dose-dependent levels of IL-15/IL-15Ralpha complexes in serum, production of IFN-gamma and activation of CD8+ T-cells and macrophages. The antitumoral efficacy of AAV-mIL15 was tested in a mouse model of metastatic colorectal cancer established by injection of MC38 cells. AAV-mIL15 treatment slightly inhibits MC38 tumor-growth and significantly increases the survival of mice. However, mIL-15 sustained expression was associated with development of side effects like hepatosplenomegaly, liver damage and the development of haematological stress, which results in the expansion of hematopoietic precursors in the bone marrow. To elucidate the mechanism, we treated IFN-gamma receptor-, RAG1-, CD1d- and uMT-deficient mice and performed adoptive transfer of bone marrow cells from WT mice to RAG1-defcient mice. We demonstrated that the side effects of murine IL-15 administration were mainly mediated by IFN-gamma producing T-cells. CONCLUSIONS: IL-15 induces the activation and survival of effector immune cells that are necessary for its antitumoral activity; but, long term exposure to IL-15 is associated with the development of important side effects mainly mediated by IFN-gamma-producing T-cells. Strategies to modulate T cell activation should be combined with IL-15 administration to reduce secondary adverse events while maintaining its antitumoral effect. PMID- 27356751 TI - In vitro studies implicate an imbalanced activation of dendritic cells in the pathogenesis of murine autoimmune pancreatitis. AB - OBJECTIVES: MRL/MpJ mice spontaneously develop an autoimmune pancreatitis (AIP) and are widely used as a model to study the genetic, molecular and immunological basis of the disease. Here, we have addressed the question whether distinctive features of their dendritic cells (DCs) may predispose MRL/MpJ mice to the chronic inflammation. METHODS: Pancreatic lesions were analyzed employing histological methods. Cohorts of young (healthy) MRL/MpJ mice, adult (sick) individuals, and AIP-resistant CAST/EiJ mice were used to establish cultures of bone marrow (BM)-derived conventional DCs (cDCs). The cells were subsequently characterized regarding the expression profile of CD markers and selected genes, proliferative activity as well as cytokine secretion. RESULTS: In pancreatic lesions, large numbers of cells expressing the murine DC marker CD11c were detected in close spatial proximity to CD3+ cells. A high percentage of BM derived cDCs from adult MRL/MpJ mice expressed typical markers of DC maturation (such as CD83) already prior to a treatment with lipopolysaccharide (LPS). After LPS-stimulation, cDC cultures of both MRL/MpJ mouse cohorts contained more mature cells, proliferated at a higher rate and secreted less interleukin-10 (but also less pro-inflammatory cytokines) than cultures of CAST/EiJ mice. Compared with corresponding cultures of the control strain, LPS-free cultured cDCs from MRL/MpJ mice expressed less mRNA of the inhibitory receptor triggering receptor expressed on myeloid cells 2 (trem2). CONCLUSIONS: BM-derived cDCs from AIP-prone MRL/MpJ mice display functional features that are compatible with the hypothesis of an imbalanced DC activation in the context of murine AIP. PMID- 27356752 TI - The modulation of Dicer regulates tumor immunogenicity in melanoma. AB - MicroRNAs (miRs) are small non-coding RNAs that regulate most cellular protein networks by targeting mRNAs for translational inhibition or degradation. Dicer, a type III endoribonuclease, is a critical component in microRNA biogenesis and is required for mature microRNA production. Abnormal Dicer expression occurs in numerous cancer types and correlates with poor patient prognosis. For example, increased Dicer expression in melanoma is associated with more aggressive tumors (higher tumor mitotic index and depth of invasion) and poor patient prognosis. However, the role that Dicer plays in melanoma development and immune evasion remains unclear. Here, we report on a newly discovered relationship between Dicer expression and tumor immunogenicity. To investigate Dicer's role in regulating melanoma immunogenicity, Dicer knockdown studies were performed. We found that B16F0-Dicer deficient cells exhibited decreased tumor growth compared to control cells and were capable of inducing anti-tumor immunity. The decrease in tumor growth was abrogated in immunodeficient NSG mice and was shown to be dependent upon CD8+ T cells. Dicer knockdown also induced a more responsive immune gene profile in melanoma cells. Further studies demonstrated that CD8+ T cells preferentially killed Dicer knockdown tumor cells compared to control cells. Taken together, we present evidence which links Dicer expression to tumor immunogenicity in melanoma. PMID- 27356753 TI - Prostate-specific antigen density values among patients with symptomatic prostatic enlargement in Nigeria. AB - BACKGROUND: This study aims to estimate the prostate-specific antigen density (PSAD) cutoff level for detecting prostate cancer (CAP) in Nigerian men with "grey zone PSA" (4-10 ng/ml) and normal digital rectal examination findings. We addressed this research question: Is the international PSAD cutoff of 0.15 ideal for detecting CAP in our symptomatic patients with "grey zone PSA?" METHODS: AIM: To estimate the prostate-specific antigen density (PSAD) cutoff level for detecting CAP in Nigerian men with "grey zone PSA" (4-10 ng/ml) and normal digital rectal examination findings. DESIGN: Prospective. SETTING: A tertiary medical center in Enugu, Nigeria. PARTICIPANTS: Two hundred and fifty-four men with either benign prostatic hyperplasia (BPH) or CAP were recruited. INTERVENTION: Patients with PSA above 4 ng/ml or abnormal digital rectal examination or hypoechoic lesion in the prostate were biopsied. OUTCOME MEASURES: PSAD and histology report of BPH or CAP. RESULTS: Ninety-seven patients had CAP while 157 had benign prostatic hyperplasia (BPH). Seventy-two patients had their serum PSA value within the range of 4.0 and 10 ng/ml. PSAD cutoff level to detect CAP was 0.04 (sensitivity 95.88 %; specificity 28.7 %). CONCLUSIONS: The PSAD cutoff level generated for Nigerian men in this study is 0.04 which is relatively different from international consensus. This PSAD cutoff level has a positive correlation with histology and could detect patients with CAP who have "grey zone PSA." PMID- 27356754 TI - Determinants of health care seeking behaviour during pregnancy in Ogun State, Nigeria. AB - BACKGROUND: In Nigeria, women too often suffer the consequences of serious obstetric complications that may lead to death. Delay in seeking care (phase I delay) is a recognized contributor to adverse pregnancy outcomes. This qualitative study aimed to describe the health care seeking practices in pregnancy, as well as the socio-cultural factors that influence these actions. METHODS: The study was conducted in Ogun State, in south-western Nigeria. Data were collected through focus group discussions with pregnant women, recently pregnant mothers, male decision-makers, opinion leaders, traditional birth attendants, health workers, and health administrators. A thematic analysis approach was used with QSR NVivo version 10. RESULTS: Findings show that women utilized multiple care givers during pregnancy, with a preference for traditional providers. There was a strong sense of trust in traditional medicine, particularly that provided by traditional birth attendants who are long-term residents in the community. The patriarchal c influenced health-seeking behaviour in pregnancy. Economic factors contributed to the delay in access to appropriate services. There was a consistent concern regarding the cost barrier in accessing health services. The challenges of accessing services were well recognised and these were greater when referral was to a higher level of care which in most cases attracted unaffordable costs. CONCLUSION: While the high cost of care is a deterrent to health seeking behaviour, the cost of death of a woman or a child to the family and community is immeasurable. The use of innovative mechanisms for health care financing may be beneficial for women in these communities to reduce the barrier of high cost services. To reduce maternal deaths all stakeholders must be engaged in the process including policy makers, opinion leaders, health care consumers and providers. Underlying socio-cultural factors, such as structure of patriarchy, must also be addressed to sustainably improve maternal health. TRIAL REGISTRATION: NCT01911494. PMID- 27356755 TI - Hotspot mutations delineating diverse mutational signatures and biological utilities across cancer types. AB - BACKGROUND: An important step towards personalizing cancer treatment is to integrate heterogeneous evidences to catalog mutational hotspots that are biologically and therapeutically relevant and thus represent where targeted therapy would likely be beneficial. However, existing methods do not sufficiently delineate varying functionality of individual mutations within the same genes. RESULTS: We observed a large discordancy of mutation rates across different mutation subtypes and tumor types, and nominated 702 hotspot mutations in 549 genes in the Catalog of Somatic Mutations in Cancer (COSMIC) by considering context specific mutation characteristics such as genes, cancer types, mutation rates, mutation subtypes and sequence contexts. We observed that hotspot mutations were highly prevalent in Non CpG-island C/G transition and transversion sequence contexts in 10 tumor types, and specific insertion hotspot mutations were enriched in breast cancer and deletion hotspot mutations in colorectal cancer. We found that the hotspot mutations nominated by our approach were significantly more conserved than non-hotspot mutations in the corresponding cancer genes. We also examined the biological significance and pharmacogenomics properties of these hotspot mutations using data in the Cancer Genome Atlas (TCGA) and the Cancer Cell-Line Encyclopedia (CCLE), and found that 53 hotspot mutations are independently associated with diverse functional evidences in 1) mRNA and protein expression, 2) pathway activity, or 3) drug sensitivity and 82 were highly enriched in specific tumor types. We highlighted the distinct functional indications of hotspot mutations under different contexts and nominated novel hotspot mutations such as MAP3K4 A1199 deletion, NR1H2 Q175 insertion, and GATA3 P409 insertion as potential biomarkers or drug targets. CONCLUSION: We identified a set of hotspot mutations across 17 tumor types by considering the background mutation rate variations among genes, tumor subtypes, mutation subtypes, and sequence contexts. We illustrated the common and distinct mutational signatures of hotspot mutations among different tumor types and investigated their variable functional relevance under different contexts, which could potentially serve as a resource for explicitly selecting targets for diagnosis, drug development, and patient management. PMID- 27356756 TI - Evolution in an extreme environment: developmental biases and phenotypic integration in the adaptive radiation of antarctic notothenioids. AB - BACKGROUND: Over the past 40 million years water temperatures have dramatically dropped in the Southern Ocean, which has led to the local extinction of most nearshore fish lineages. The evolution of antifreeze glycoproteins in notothenioids, however, enabled these ancestrally benthic fishes to survive and adapt as temperatures reached the freezing point of seawater (-1.86 degrees C). Antarctic notothenioids now represent the primary teleost lineage in the Southern Ocean and are of fundamental importance to the local ecosystem. The radiation of notothenioids has been fostered by the evolution of "secondary pelagicism", the invasion of pelagic habitats, as the group diversified to fill newly available foraging niches in the water column. While elaborate craniofacial modifications have accompanied this adaptive radiation, little is known about how these morphological changes have contributed to the evolutionary success of notothenioids. RESULTS: We used a 3D-morphometrics approach to investigate patterns of morphological variation in the craniofacial skeleton among notothenioids, and show that variation in head shape is best explained by divergent selection with respect to foraging niche. We document further an accelerated rate of morphological evolution in the icefish family Channichthyidae, and show that their rapid diversification was accompanied by the evolution of relatively high levels of morphological integration. Whereas most studies suggest that extensive integration should constrain phenotypic evolution, icefish stand out as a rare example of increased integration possibly facilitating evolutionary potential. Finally, we show that the unique feeding apparatus in notothenioids in general, and icefish in particular, can be traced to shifts in early developmental patterning mechanisms and ongoing growth of the pharyngeal skeleton. CONCLUSION: Our work suggests that ecological opportunity is a major factor driving craniofacial variation in this group. Further, the observation that closely related lineages can differ dramatically in integration suggests that this trait can evolve quickly. We propose that the evolution of high levels of phenotypic integration in icefishes may be considered a key innovation that facilitated their morphological evolution and subsequent ecological expansion. PMID- 27356757 TI - Tissue metabolic profiling of human gastric cancer assessed by (1)H NMR. AB - BACKGROUND: Gastric cancer is the fourth most common cancer and the second most deadly cancer worldwide. Study on molecular mechanisms of carcinogenesis will play a significant role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to identify the potential biomarkers for the early diagnosis of gastric cancer. METHODS: In this study, we reported the metabolic profiling of tissue samples on a large cohort of human gastric cancer subjects (n = 125) and normal controls (n = 54) based on (1)H nuclear magnetic resonance ((1)H NMR) together with multivariate statistical analyses (PCA, PLS-DA, OPLS-DA and ROC curve). RESULTS: The OPLS-DA model showed adequate discrimination between cancer tissues and normal controls, and meanwhile, the model excellently discriminated the stage-related of tissue samples (stage I, 30; stage II, 46; stage III, 37; stage IV, 12) and normal controls. A total of 48 endogenous distinguishing metabolites (VIP > 1 and p < 0.05) were identified, 13 of which were changed with the progression of gastric cancer. These modified metabolites revealed disturbance of glycolysis, glutaminolysis, TCA, amino acids and choline metabolism, which were correlated with the occurrence and development of human gastric cancer. The receiver operating characteristic diagnostic AUC of OPLS-DA model between cancer tissues and normal controls was 0.945. And the ROC curves among different stages cancer subjects and normal controls were gradually improved, the corresponding AUC values were 0.952, 0.994, 0.998 and 0.999, demonstrating the robust diagnostic power of this metabolic profiling approach. CONCLUSION: As far as we know, the present study firstly identified the differential metabolites in various stages of gastric cancer tissues. And the AUC values were relatively high. So these results suggest that the metabolic profiling of gastric cancer tissues has great potential in detecting this disease and helping to understand its underlying metabolic mechanisms. PMID- 27356759 TI - Mechanical aortic valve without anticoagulation for 33 years in a Yemeni man: a case report. AB - BACKGROUND: Mechanical prosthetic heart valves have been used for many decades to replace damaged native valves. Guidelines mandate the use of anticoagulant therapy in patients with mechanical prosthetic valves of any type, irrespective of the position in the heart. The rationale for this is to prevent valve thrombosis and thromboembolic complications without increasing the risk of excess bleeding. We report a case involving a patient with a functioning aortic mechanical valve without any anticoagulation therapy for 33 years. CASE PRESENTATION: A 46-year-old Yemeni man had an aortic valve replacement, using a St Jude Medical mechanical valve, 33 years ago due to aortic regurgitation grade III-IV of his native valve as a result of rheumatic heart disease. His anticoagulant therapy of Syncumar (acenocoumarol which is a derivative of coumarin) was discontinued 4 months after surgery, and he was sustained on aspirin and digoxin. He presented to our cardiac clinic 33 years later with palpitations, which had started 2 weeks previously. On clinical examination, his condition was fair with a New York Heart Association functional classification of I. He was in sinus rhythm and had normal heart size, as shown on chest X-ray. Echocardiography revealed normal heart chamber dimensions and normal left ventricular systolic and diastolic function. His mean transaortic gradient was 12.58 mmHg and the calculated aortic valve area was 1.44 cm(2). He was started on anticoagulant therapy. CONCLUSIONS: Only a few cases of well-functioning mechanical valves without the use of anticoagulant therapy for many years have been reported. Our patient is one such case who used only aspirin for 33 years. Further research is needed to understand the interpersonal variations and other unexplored factors in anticoagulant therapy for patients with mechanical prosthetic heart valves. PMID- 27356758 TI - Multicenter Female Fabry Study (MFFS) - clinical survey on current treatment of females with Fabry disease. AB - BACKGROUND: The aim of the present study was to assess manifestations of and applied treatment concepts for females with Fabry disease (FD) according to the current European Fabry Guidelines. METHODS: Between 10/2008 and 12/2014, data from the most recent visit of 261 adult female FD patients from six German Fabry centers were retrospectively analyzed. Clinical presentation and laboratory data, including plasma lyso-Gb3 levels were assessed. RESULTS: Fifty-five percent of females were on enzyme replacement therapy (ERT), according to recent European FD guidelines. Thirty-three percent of females were untreated although criteria for ERT initiation were fulfilled. In general, the presence of left ventricular hypertrophy (LVH) seemed to impact more on ERT initiation than impaired renal function. In ERT-naive females RAAS blockers were more often prescribed if LVH was present rather than albuminuria. Affected females with missense mutations showed a similar disease burden compared to females with nonsense mutations. Elevated plasma lyso-Gb3 levels in ERT-naive females seem to be a marker of disease burden, since patients showed comparable incidences of organ manifestations even if they were ~8 years younger than females with normal lyso Gb3 levels. CONCLUSION: The treatment of the majority of females with FD in Germany is in line with the current European FD guidelines. However, a relevant number of females remain untreated despite organ involvement, necessitating a careful reevaluation of these females. PMID- 27356760 TI - AirLab: a cloud-based platform to manage and share antibody-based single-cell research. AB - Single-cell analysis technologies are essential tools in research and clinical diagnostics. These methods include flow cytometry, mass cytometry, and other microfluidics-based technologies. Most laboratories that employ these methods maintain large repositories of antibodies. These ever-growing collections of antibodies, their multiple conjugates, and the large amounts of data generated in assays using specific antibodies and conditions makes a dedicated software solution necessary. We have developed AirLab, a cloud-based tool with web and mobile interfaces, for the organization of these data. AirLab streamlines the processes of antibody purchase, organization, and storage, antibody panel creation, results logging, and antibody validation data sharing and distribution. Furthermore, AirLab enables inventory of other laboratory stocks, such as primers or clinical samples, through user-controlled customization. Thus, AirLab is a mobile-powered and flexible tool that harnesses the capabilities of mobile tools and cloud-based technology to facilitate inventory and sharing of antibody and sample collections and associated validation data. PMID- 27356761 TI - Synthetic analogues of Fe(ii)-Fe(iii) minerals containing a pentagonal 'Cairo' magnetic lattice. AB - Versiliaite and apuanite are two minerals containing Fe(2+) and Fe(3+) in a low dimensional structure exhibiting chains of edge-linked FeO6 octahedra. The chemistry of these minerals has not been fully examined because of their rarity. We demonstrate that chemical synthesis of these minerals is possible to allow measurement of their magnetic properties and a more complete description of their structural features using neutron powder diffraction. We also show that chemical manipulation is possible to provide isostructural phases with different chemical compositions. PMID- 27356762 TI - Can nitro groups really anchor onto TiO2? Case study of dye-to-TiO2 adsorption using azo dyes with NO2 substituents. AB - The nitro group has recently been suggested as a new type of anchor for dye sensitized solar cells (DSSCs) and has shown promising optoelectronic properties. Considering the excellent electron withdrawing ability of the nitro group and wider materials selection brought about by this substituent, it is helpful to evaluate the interfacial structures and photophysics of more organic dyes where NO2 poses as the dye-to-TiO2 anchor. A computational study on a family of azo dyes bearing a nitro group is presented, where the effect of certain side groups on their optical properties is examined. Both isolated dye molecules and dye/TiO2 nanocomposites are studied via density functional theory and time-dependent density functional theory, with complementary experimental UV/vis absorption spectroscopy and photovoltaic device testing. Results demonstrate that these nitro-containing dyes prefer a monodentate anchoring mode on a TiO2 cluster. These nitro dyes reveal weak, but non-negligible, adsorption onto TiO2; yet, very low photovoltaic performance once incorporated into a DSSC device. This poor delivery of nitro groups as DSSC anchors is ostensibly inconsistent with previous findings; but is rationalized via the "auxiliary anchor" concept. PMID- 27356763 TI - Transcriptome sequencing and marker development in winged bean (Psophocarpus tetragonolobus; Leguminosae). AB - Winged bean, Psophocarpus tetragonolobus (L.) DC., is similar to soybean in yield and nutritional value but more viable in tropical conditions. Here, we strengthen genetic resources for this orphan crop by producing a de novo transcriptome assembly and annotation of two Sri Lankan accessions (denoted herein as CPP34 [PI 491423] and CPP37 [PI 639033]), developing simple sequence repeat (SSR) markers, and identifying single nucleotide polymorphisms (SNPs) between geographically separated genotypes. A combined assembly based on 804,757 reads from two accessions produced 16,115 contigs with an N50 of 889 bp, over 90% of which has significant sequence similarity to other legumes. Combining contigs with singletons produced 97,241 transcripts. We identified 12,956 SSRs, including 2,594 repeats for which primers were designed and 5,190 high-confidence SNPs between Sri Lankan and Nigerian genotypes. The transcriptomic data sets generated here provide new resources for gene discovery and marker development in this orphan crop, and will be vital for future plant breeding efforts. We also analyzed the soybean trypsin inhibitor (STI) gene family, important plant defense genes, in the context of related legumes and found evidence for radiation of the Kunitz trypsin inhibitor (KTI) gene family within winged bean. PMID- 27356764 TI - Resting State Brain Network Disturbances Related to Hypomania and Depression in Medication-Free Bipolar Disorder. AB - Research on resting functional brain networks in bipolar disorder (BP) has been unable to differentiate between disturbances related to mania or depression, which is necessary to understand the mechanisms leading to each state. Past research has also been unable to elucidate the impact of BP-related network disturbances on the organizational properties of the brain (eg, communication efficiency). Thus, the present work sought to isolate network disturbances related to BP, fractionate these into components associated with manic and depressive symptoms, and characterize the impact of disturbances on network function. Graph theory was used to analyze resting functional magnetic resonance imaging data from 60 medication-free patients meeting the criteria for BP and either a current hypomanic (n=30) or depressed (n=30) episode and 30 closely age/sex-matched healthy controls. Correction for multiple comparisons was carried out. Compared with controls, BP patients evidenced hyperconnectivity in a network involving right amygdala. Fractionation revealed that (hypo)manic symptoms were associated with hyperconnectivity in an overlapping network and disruptions in the brain's 'small-world' network organization. Depressive symptoms predicted hyperconnectivity in a network involving orbitofrontal cortex along with a less resilient global network organization. Findings provide deeper insight into the differential pathophysiological processes associated with hypomania and depression, along with the particular impact these differential processes have on network function. PMID- 27356766 TI - Decadal drought deaccelerated the increasing trend of annual net primary production in tropical or subtropical forests in southern China. AB - Previous investigations have identified that the effects of climate change on net primary production (NPP) of global forests have varied both spatially and temporally, and that warming has increased the NPP for many forests. However, other factors, such as available soil water for plant growth, could limit these incremental responses to warming. In our investigation we have quantified the responses of NPP of tropical or subtropical forests in southern China to warming and drought stress over the past three decades (1981 to 2012) using data from five forest research stations and satellite measurements. NPP, mean annual temperature (MAT) and annual days without rainfall showed an increase of 0.076 g C m(-2) a(-2) (standardized), 0.057 degrees C a(-1) (standardized) and 0.067 d a(-1) (standardized) during the study period, respectively. However, incremental NPP was deaccelerated at a rate of approximately 20.8% per decade. This deacceleration was primarily caused by a decrease in available soil water which resulted from warming (mainly occurring in winter and autumn) and the changes in rainfall pattern. The result indicates that intensifying drought stress would limit future increases of forest NPP in southern China. PMID- 27356765 TI - Integrative analysis of cancer genes in a functional interactome. AB - The post-genomic era has resulted in the accumulation of high-throughput cancer data from a vast array of genomic technologies including next-generation sequencing and microarray. As such, the large amounts of germline variant and somatic mutation data that have been generated from GWAS and sequencing projects, respectively, show great promise in providing a systems-level view of these genetic aberrations. In this study, we analyze publicly available GWAS, somatic mutation, and drug target data derived from large databanks using a network-based approach that incorporates directed edge information under a randomized network hypothesis testing procedure. We show that these three classes of disease associated nodes exhibit non-random topological characteristics in the context of a functional interactome. Specifically, we show that drug targets tend to lie upstream of somatic mutations and disease susceptibility germline variants. In addition, we introduce a new approach to measuring hierarchy between drug targets, somatic mutants, and disease susceptibility genes by utilizing directionality and path length information. Overall, our results provide new insight into the intrinsic relationships between these node classes that broaden our understanding of cancer. In addition, our results align with current knowledge on the therapeutic actionability of GWAS and somatic mutant nodes, while demonstrating relationships between node classes from a global network perspective. PMID- 27356767 TI - Coronary vasculature patterning requires a novel endothelial ErbB2 holoreceptor. AB - Organogenesis and regeneration require coordination of cellular proliferation, regulated in part by secreted growth factors and cognate receptors, with tissue nutrient supply provided by expansion and patterning of blood vessels. Here we reveal unexpected combinatorial integration of a growth factor co-receptor with a heterodimeric partner and ligand known to regulate angiogenesis and vascular patterning. We show that ErbB2, which can mediate epidermal growth factor (EGF) and neuregulin signalling in multiple tissues, is unexpectedly expressed by endothelial cells where it partners with neuropilin 1 (Nrp1) to form a functional receptor for the vascular guidance molecule semaphorin 3d (Sema3d). Loss of Sema3d leads to improper patterning of the coronary veins, a phenotype recapitulated by endothelial loss of ErbB2. These findings have implications for possible cardiovascular side-effects of anti-ErbB2 therapies commonly used for cancer, and provide an example of integration at the molecular level of pathways involved in tissue growth and vascular patterning. PMID- 27356768 TI - Temporal Lobe Epilepsy Alters Auditory-motor Integration For Voice Control. AB - Temporal lobe epilepsy (TLE) is the most common drug-refractory focal epilepsy in adults. Previous research has shown that patients with TLE exhibit decreased performance in listening to speech sounds and deficits in the cortical processing of auditory information. Whether TLE compromises auditory-motor integration for voice control, however, remains largely unknown. To address this question, event related potentials (ERPs) and vocal responses to vocal pitch errors (1/2 or 2 semitones upward) heard in auditory feedback were compared across 28 patients with TLE and 28 healthy controls. Patients with TLE produced significantly larger vocal responses but smaller P2 responses than healthy controls. Moreover, patients with TLE exhibited a positive correlation between vocal response magnitude and baseline voice variability and a negative correlation between P2 amplitude and disease duration. Graphical network analyses revealed a disrupted neuronal network for patients with TLE with a significant increase of clustering coefficients and path lengths as compared to healthy controls. These findings provide strong evidence that TLE is associated with an atypical integration of the auditory and motor systems for vocal pitch regulation, and that the functional networks that support the auditory-motor processing of pitch feedback errors differ between patients with TLE and healthy controls. PMID- 27356769 TI - Quantitative and compositional responses of ammonia-oxidizing archaea and bacteria to long-term field fertilization. AB - Archaeal (AOA) and bacterial (AOB) ammonia-oxidizer responses to long-term field fertilization in a Mollisol soil were assessed through pyrosequencing of amoA genes. Long-term fertilization treatments including chemical fertilizer (NPK), NPK plus manure (NPKM), and no fertilization over 23 years altered soil properties resulting in significant shifts in AOA and AOB community composition and abundance. NPK exhibited a strong influence on AOA and AOB composition while the addition of manure neutralized the community change induced by NPK. NPK also led to significant soil acidification and enrichment of Nitrosotalea. Nitrosospira cluster 9 and 3c were the most abundant AOB populations with opposing responses to fertilization treatments. NPKM had the largest abundance of ammonia-oxidizers and highest potential nitrification activity (PNA), suggesting high N loss potential due to a doubling of nutrient input compared to NPK. PNA was strongly correlated to AOA and AOB community composition indicating that both were important in ammonium oxidization in this Mollisol soil. Total N and organic C were the most important factors driving shifts in AOA and AOB community composition. The AOA community was strongly correlated to the activities of all sugar hydrolysis associated soil enzymes and was more responsive to C and N input than AOB. PMID- 27356771 TI - Protein structural changes during processing of vegetable feed ingredients used in swine diets: implications for nutritional value. AB - Protein structure influences the accessibility of enzymes for digestion. The proportion of intramolecular beta-sheets in the secondary structure of native proteins has been related to a decrease in protein digestibility. Changes to proteins that can be considered positive (for example, denaturation and random coil formation) or negative (for example, aggregation and Maillard reactions) for protein digestibility can occur simultaneously during processing. The final result of these changes on digestibility seems to be a counterbalance of the occurrence of each phenomenon. Occurrence of each phenomenon depends on the conditions applied, but also on the source and type of the protein that is processed. The correlation between denaturation enthalpy after processing and protein digestibility seems to be dependent on the protein source. Heat seems to be the processing parameter with the largest influence on changes in the structure of proteins. The effect of moisture is usually limited to the simultaneous application of heat, but increasing level of moisture during processing usually increases structural changes in proteins. The effect of shear on protein structure is commonly studied using extrusion, although the multifactorial essence of this technology does not allow disentanglement of the separate effects of each processing parameter (for example, heat, shear, moisture). Although most of the available literature on the processing of feed ingredients reports effects on protein digestibility, the mechanisms that explain these effects are usually lacking. Clarifying these mechanisms could aid in the prediction of the nutritional consequences of processing conditions. PMID- 27356770 TI - Impact of dietary resistant starch type 4 on human gut microbiota and immunometabolic functions. AB - Dietary modulation of the gut microbiota impacts human health. Here we investigated the hitherto unknown effects of resistant starch type 4 (RS4) enriched diet on gut microbiota composition and short-chain fatty acid (SCFA) concentrations in parallel with host immunometabolic functions in twenty individuals with signs of metabolic syndrome (MetS). Cholesterols, fasting glucose, glycosylated haemoglobin, and proinflammatory markers in the blood as well as waist circumference and % body fat were lower post intervention in the RS4 group compared with the control group. 16S-rRNA gene sequencing revealed a differential abundance of 71 bacterial operational taxonomic units, including the enrichment of three Bacteroides species and one each of Parabacteroides, Oscillospira, Blautia, Ruminococcus, Eubacterium, and Christensenella species in the RS4 group. Gas chromatography-mass spectrometry revealed higher faecal SCFAs, including butyrate, propionate, valerate, isovalerate, and hexanoate after RS4 intake. Bivariate analyses showed RS4-specific associations of the gut microbiota with the host metabolic functions and SCFA levels. Here we show that dietary RS4 induced changes in the gut microbiota are linked to its biological activity in individuals with signs of MetS. These findings have potential implications for dietary guidelines in metabolic health management. PMID- 27356772 TI - Central European parasitic flatworms of the family Renicolidae Dollfus, 1939 (Trematoda: Plagiorchiida): molecular and comparative morphological analysis rejects the synonymization of Renicola pinguis complex suggested by Odening. AB - The Renicolidae are digenean parasites of piscivorous and molluscivorous birds. Although they exhibit few morphological autapomorphies and are highly variable, the numerous suggested re-classifications within the family have never been supported by any molecular analyses. We address the possible synonymization of species within the Renicola pinguis complex suggested previously by Odening. We provide and analyse sequences of two nuclear (ITS2, 28S rDNA) and two mitochondrial (CO1, ND1) DNA loci of central European species of the Renicolidae, namely Renicola lari, Renicola pinguis and Renicola sternae sp. n., and we also provide first sequences of Renicola sloanei. The combined molecular and comparative morphological analysis confirms the previously questioned validity of the three Renicola spp. of highly similar morphology, which display strict niche separation in terms of host specificity and selectivity. We identify two previously unreported clades within the genus Renicola; however, only one of them is supported by the analysis of adult worms. We also provide comparative measurements of the three examined closely related central European renicolids, and describe the newly proposed tern-specialized species Renicola sternae sp. n., which was previously repeatedly misidentified as Renicola paraquinta. Based on the extensive dataset collected in 1962-2015, we update the host spectrum of Renicolidae parasitizing central European birds (Renicola bretensis, R. lari, Renicola mediovitellata, R. pinguis, Renicola secunda and R. sternae sp. n.) and discuss their host-specific prevalence and intensity of infections. PMID- 27356773 TI - Aspirin inhibits glucose-6-phosphate dehydrogenase activity in HCT 116 cells through acetylation: Identification of aspirin-acetylated sites. AB - Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the first reaction in the pentose phosphate pathway, and generates ribose sugars, which are required for nucleic acid synthesis, and nicotinamide adenine dinucleotide phosphate (NADPH), which is important for neutralization of oxidative stress. The expression of G6PD is elevated in several types of tumor, including colon, breast and lung cancer, and has been implicated in cancer cell growth. Our previous study demonstrated that exposure of HCT 116 human colorectal cancer cells to aspirin caused acetylation of G6PD, and this was associated with a decrease in its enzyme activity. In the present study, this observation was expanded to HT-29 colorectal cancer cells, in order to compare aspirin-mediated acetylation of G6PD and its activity between HCT 116 and HT-29 cells. In addition, the present study aimed to determine the acetylation targets of aspirin on recombinant G6PD to provide an insight into the mechanisms of inhibition. The results demonstrated that the extent of G6PD acetylation was significantly higher in HCT 116 cells compared with in HT-29 cells; accordingly, a greater reduction in G6PD enzyme activity was observed in the HCT 116 cells. Mass spectrometry analysis of aspirin-acetylated G6PD (isoform a) revealed that aspirin acetylated a total of 14 lysine residues, which were dispersed throughout the length of the G6PD protein. One of the important amino acid targets of aspirin included lysine 235 (K235, in isoform a) and this corresponds to K205 in isoform b, which has previously been identified as being important for catalysis. Acetylation of G6PD at several sites, including K235 (K205 in isoform b), may mediate inhibition of G6PD activity, which may contribute to the ability of aspirin to exert anticancer effects through decreased synthesis of ribose sugars and NADPH. PMID- 27356774 TI - Application of Mitochondria-Targeted Pharmaceuticals for the Treatment of Heart Disease. AB - BACKGROUND: Mitochondria fulfill the massive energy demands of the human heart through oxidative phosphorylation (OXPHOS) which couples nutrient oxidation and the reduction of molecular oxygen (O2) to the phosphorylation of ADP. Reactive oxygen species (ROS) are also generated during OXPHOS which can be damaging at high levels but serve as secondary messengers when produced in a controlled manner. METHODS: Here, I review how disruption of control over mitochondrial ROS production can lead to the pathogenesis of a range of cardiovascular diseases (CVD) including decompensated left ventricular hypertrophy, alcoholic and diabetic hypertrophy, myocardial infarction (MI), ischemic-reperfusion injury (IR), and heart failure. In particular I focus on the function of protein S glutathionylation (PGlu) reactions, a rapid and reversible redox signaling mechanism that involves the conjugation and removal of glutathione from cysteine switches, in the modulation of ROS production in myocardial mitochondria and how these reactions become deregulated in heart disease. I also discuss the use of mitochondria penetrating antioxidants in the treatment of heart disease. RESULTS: I propose that heart disease related to deregulated PGlu reactions can be treated with a novel and hypothetical class of mitochondria penetrating reduced glutathione (GSH) molecules called MitoGSH. This synthetic form of GSH can be tagged with either SS peptides or triphenylphosphonium ions to ensure accumulation in mitochondria which could restore glutathione levels and preserve redox buffering networks. CONCLUSION: Mitochondria penetrating antioxidants have been shown to be efficient at restoring mitochondrial antioxidant defense in CVD. However, CVD and various other disorders are associated with a depletion of GSH pools. Use of mitochondria-targeted GSH analogs could serve as a more efficient means of treating heart disease since it would allow for the direct restoration of GSH levels and preserve mitochondrial redox buffering and signaling capacity. PMID- 27356775 TI - The 9p21 Locus and its Potential Role in Atherosclerosis Susceptibility; Molecular Mechanisms and Clinical Implications. AB - Cardiovascular disease (CVD) is the leading cause of global mortality. Although extensive efforts have been made to identify valid biomarkers for CVD risk, relatively few are of proven clinical utility. It is recognized that genetic factors play a major role in determining the susceptibility to CVD. Recent genome wide-association-studies have demonstrated common genetic variants in a region on chromosome 9p21 associated with an increased risk of CVD. Several genetic polymorphisms have been identified in this region that are highly associated with CVD, and these are clustered around the gene loci for CDKN2B (coding for p15ink4b), CDKN2A (coding for p16ink4a and p14ARF) and the 3' end of CDKN2BAS, which has been termed antisense noncoding RNA in the INK4 locus (ANRIL). Targeted deletion of the 9p21 locus reduces the cardiac expression of CDKN2A/B and is the most frequent mechanism for methylthioadenosine phosphorylase inactivation, leading to a less stable plaque phenotype in the artery. Further investigations will be essential to explore the clinical utility of emerging-markers in larger and multicenter setting in order to establish their values for risk stratification or prediction a chance of future CVD events. The aim of the current review was to provide an overview of the possible molecular mechanisms by which the chromosome 9p21 locus may confer CVD risk, and the consequential clinical implications with particular emphasis on preclinical/clinical trials on genetic changes of this locus and CVD risk. PMID- 27356776 TI - Shear Stress-sensitive Carriers for Localized Drug Delivery. AB - Stenosis of the critical blood vessels, which occurs in a variety of cardiovascular and cerebrovascular diseases, is one of leading causes of death in the world. Vascular stenosis will significantly alter the hemodynamic features in the vessel. Hemodynamic shear stress, one of the most important physical parameters of blood flow, will be dramatically elevated at the stenotic site. When platelets flow through the constricted site, they will sense these abnormally high shear stresses, and then respond by activating, sticking to the vascular wall, and aggregating at these sites. The shear-dependent platelet activation inspired a novel targeting platform-shear stress activated drug targeting delivery. The shear-activated drug delivery systems preferentially release their content under elevated shear stress, providing a novel approach to cure various diseases, in particular, cardiovascular diseases. In this review, we, on one hand, introduced the features of hemodynamic shear stress under both physiological and pathological conditions. On the other hand, we summarized the carriers displaying sensitivity to shear stress, such as liposomes, aggregations, gels, emulsions, in addition to the factors affecting the mechanical properties of them. Lastly, the clinical applications and prospects of this novel drug targeting strategy were discussed. It is hoped that, with a better understanding of shear stress-sensitive carriers and their targeted principle, a novel targeted drug delivery strategy will be one day applied in the clinics of the future. PMID- 27356777 TI - Development of a Mouse Model of Shiga Toxin 2 (Stx2) Intoxication for Testing Therapeutic Agents Against Hemolytic Uremic Syndrome (HUS). AB - BACKGROUND: Hemolytic Uremic Syndrome (HUS) caused by infections with Shiga toxin (Stx)-producing E. coli is a life-threatening complication characterized by acute renal failure, thrombocytopenia and hemolytic anemia. Stx is the main pathogenic factor. Therefore, the mouse model by intravenous administration of a single lethal dose of Stx is often used to explore its pathogenic mechanisms. OBJECTIVE: The aim of this work was to develop an alternative mouse model of Stx type 2 (Stx2) intoxication to evaluate new therapeutic strategies. METHODS AND RESULTS: One lethal dose of Stx2 was divided in four daily doses. We observed a dose dependent toxicity characterized by neutrophilia, leukocytopenia and renal damage. Most importantly, we demonstrated that the polyclonal anti-Stx2 serum was able to protect mice from fatal evolution even when administered together the third dose of Stx2. CONCLUSION: This model would provide an advantage for evaluation of therapeutic strategies. Furthermore, the results presented herein suggest that appropriate treatment with anti-Stx2 agents following the appearance of initial clinical signs may block the ongoing outcome or may alleviate disease in patients who have just been diagnosed with HUS. However, the delay in the onset of therapy would be unsafe. PMID- 27356778 TI - Alkaloids: An Emerging Antibacterial Modality Against Methicillin Resistant Staphylococcus aureus. AB - Methicillin-Resistant Staphylococcus aureus (MRSA) is a Gram-positive bacterium which causes community and hospital-acquired infections. Synthetic drug/antibiotic treatment for MRSA-related infections is becoming less effective and natural products may be an emerging new alternative for future antibacterial drug development. Alkaloids are a class of natural compounds which are known for their phytochemistry and pharmacology. This review focuses on 32 alkaloids isolated from various plants that showed marked antibacterial activity against MRSA by acting through different mechanisms such as inhibition of pyruvate kinase, Quorum quenching effect, alteration in efflux pump in MRSA and intercalating of bacterial DNA, to name just a few. In addition, the use of recent plant alkaloids against clinical isolates of MRSA has also been discussed. PMID- 27356779 TI - Photodynamic therapy in lupus miliaris disseminatus faciei's scars. AB - Lupus miliaris disseminatus faciei is an uncommon granulomatous inflammatory disease, characterized by multiple, monomorphic, reddish translucent papules and nodules, mainly located on the face. Several therapeutic options have been employed with variable results, leaving residual disfiguring scars. On this topic, we report a case of significant improvement of red-atrophic scars in a 54 year-old male after three sessions of photodynamic therapy with 10% aminolevulinic acid. Owing to the high safety profile and the excellent cosmetic result, photodynamic therapy may be considered a useful tool to both prevent and treat undesirable scarring. PMID- 27356780 TI - Biological effects of eukaryotic recombinant plasmid pReceiver-M61-BAI-1 transfection on T24 cells and HUVECs. AB - The aim of the current study was to investigate the biological effect on T24 cells and human umbilical vein endothelial cells (HUVECs) of transfection with brain-specific angiogenesis inhibitor-1 (BAI-1). The recombinant plasmid pReceiver-M61-BAI-1 was transfected into human superficial bladder tumor cells (T24) and HUVECs, in parallel with the vector control. mRNA and protein expression levels of BAI-1 were then detected by quantitative polymerase chain reaction (qPCR) and western blotting, respectively. Cell apoptosis of T24 cells and HUVECs prior and subsequent to transfection with BAI-1 was analyzed by flow cytometric analysis. Proliferation of T24 cells and HUVECs prior and subsequent to transfection of BAI-1 was assessed by the MTT method. T24 cells and HUVECs transfected with pReceiver-M61-BA1-1 were classed as the experimental group; T24 cells and HUVECs transfected with p-Receiver-M61 were the control group. qPCR and western blotting methods confirmed that there was positive expression of BAI-1 in T24 cells and HUVECs transfected with pReceiver-M61-BAI-1, however BAI-1 was not expressed in T24 cells and HUVECs transfected with pReceiver-M61. The results of the MTT assay demonstrated that absorbance was markedly reduced in HUVECs at 12, 48 and 72 h subsequent to transfection with pReceiver-M61-BAI-1 when compared with that of the control group and in T24 cells transfected with p-Receiver-M61 BAI-1. Furthermore, flow cytometry results also indicated that the apoptotic rate of HUVECs transfected with p-Receiver-M61-BAI-1 was significantly increased compared with that of the control group and T24 cells transfected with p-Receiver M61-BAI-1. BAI-1 was observed to markedly inhibit the proliferation of vascular endothelial cells in vitro, however, no direct inhibition by BAI-1 was observed in T24 cells. In conclusion, BAI-1 is suggested to be a potential novel therapautic target for the inhibition of tumor neovascularization. PMID- 27356781 TI - Oncologists' perceived barriers to an expanded role for primary care in breast cancer survivorship care. AB - Concern exists about the sustainability of traditional, oncologist-led models of breast cancer survivorship care. However, many oncologists are hesitant about deferring survivorship care to primary care providers (PCPs). Our objective was to examine oncologists' perceptions of the role PCPs play in breast cancer survivorship and the rationale underlying these perceptions. One-on-one interviews with medical, radiation, and surgical oncologists in Wisconsin were conducted (n = 35) and transcribed. Data analysis was performed using an inductive approach to content analysis. Oncologist-perceived barriers included: PCP's level of experience with cancer care; Lack of PCP comfort in providing survivorship care; Existing demands on PCPs' time; Patient preference for oncology-led survivorship care. Oncologists described familiarity and trust in individual PCPs as factors that could mitigate barriers and lead to increased PCP involvement in survivorship care. Although a number of perceived barriers to PCP participation in survivorship were identified by Wisconsin oncologists, our findings support the direction of ongoing initiatives to facilitate PCP involvement. Our findings also suggest that early PCP involvement in survivorship may increase PCP comfort and patients' trust in PCPs in this role. The identified barrier most challenging to address may be the limited capacity of the current primary care system to manage follow-up for breast cancer survivors. PMID- 27356782 TI - Organic Dots Based on AIEgens for Two-Photon Fluorescence Bioimaging. AB - Two-photon fluorescence imaging technique is a powerful bioanalytical approach in terms of high photostability, low photodamage, high spatiotemporal resolution. Recently, fluorescent organic dots comprised of organic emissive cores and a polymeric matrix are emerging as promising contrast reagents for two-photon fluorescence imaging, owing to their numerous merits of high and tunable fluorescence, good biocompatibility, strong photobleaching resistance, and multiple surface functionality. The emissive core is crucial for organic dots to get high brightness but many conventional chromophores often encounter a severe problem of fluorescence quenching when they form aggregates. To solve this problem, fluorogens featuring aggregation-induced emission (AIE) can fluoresce strongly in aggregates, and thus become ideal candidates for fluorescent organic dots. In addition, two-photon absorption property of the dots can be readily improved by just increase loading contents of AIE fluorogen (AIEgen). Hence, organic dots based on AIEgens have exhibited excellent performances in two-photon fluorescence in vitro cellular imaging, and in vivo vascular architecture visualization of mouse skin, muscle, brain and skull bone. In view of the rapid advances in this important research field, here, we highlight representative fluorescent organic dots with an emissive core of AIEgen aggregate, and discuss their great potential in bioimaging applications. PMID- 27356784 TI - [Prediction and management of peri-operative complications of spinal deformity surgery]. PMID- 27356785 TI - [Mitral regurgitation: a new predictor of the effect of cardiac resynchronization therapy]. PMID- 27356783 TI - Impact of sarcopenia on treatment tolerance in United States veterans with diffuse large B-cell lymphoma treated with CHOP-based chemotherapy. AB - While sarcopenia has been associated with decreased overall survival in diffuse large B-cell (DLBCL) patients, the impact of sarcopenia on treatment tolerance has not been well-studied. We evaluated the association of sarcopenia with febrile neutropenia hospitalization, treatment-related mortality, and ability to complete standard number of cycles in a retrospective cohort of United States veterans diagnosed with DLBCL between 1998 and 2008 and treated with cyclophosphamide, doxorubicin, vincristine, and prednisone, with or without rituximab. Baseline body composition parameters were evaluated using computed tomography analysis. In total, 522 patients were included in the study, of whom 245 (47%) had baseline sarcopenia. After controlling for other variables, baseline sarcopenia was independently associated with increased risk of febrile neutropenia hospitalization (adjusted Odds Ratio (aOR) 1.64, 95% confidence interval (CI) 1.01-2.65) and inability to complete standard number of treatment cycles (aOR 1.49, 95% CI 1.02-2.16) compared with no baseline sarcopenia. There was a non-statistically significant trend toward higher treatment-related mortality in sarcopenic patients than non-sarcopenic patients (aOR 1.77, 95% CI 0.92-3.41). Sarcopenia is associated with increased risk of treatment intolerance and may be useful in guiding treatment planning and supportive care measures. Am. J. Hematol. 91:1002-1007, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27356786 TI - [Rules of anatomic morphology changes between the vertebral artery tortuosity and transverse foramen]. AB - OBJECTIVE: To explore the rules of the anatomic morphology between vertebral artery tortuosity and transverse foramen. METHODS: From January 2012 to December 2015, 60 patients with vertebral artery tortuosity by means of analyzing the image data and basic clinic information as the observation group, and 50 patients randomly selected exclusive of vertebral artery tortuosity, absence of vertebral artery, vertebral artery aneurysm, cervical decomposition incomplete deformity and oral cavity prosthesis artifacts as the control group, the basic clinical information was collected; the transverse foramen area (TF) and vertebral artery cross-sectional area (VA) of the vertebral artery were measured in the observation group and the control group; internal diameter of vertebral artery tortuosity, length of vertebral artery were measured and; twisting coefficient (s)of the vertebral artery was calculated.Then the difference of the above mentioned statistics was acquired. RESULTS: The C4 TF (25.91+/-10.13) mm and C6 TF(31.93+/-17.91) mm of the affected segment of the observation group were significantly higher than those in the control group[(22.11+/-8.67) mm, (27.19+/ 7.89) mm] (P<0.05); VA and TF were positively correlated.The average age[(68.25+/ 12.03) years], blood pressure (45 cases)of the observation group and the proportion of the menopausal women (39 cases)were higher than those in the control group[(61.32+/-11.32) years, 23/22](P<0.05). CONCLUSIONS: The area of transverse foramen of C4 and C6 could be affected by vertebral artery tortuosity. It might be related to the occurrence of bone degeneration around C6 and C4.The risk factors of the expansion of the transverse foramen might be advanced age, hypertension and menopausal women. PMID- 27356787 TI - [Effects of pelvic balance after posterior reduction of balanced L5-S1 III-grade isthmic spondylolisthesis in adults]. AB - OBJECTIVE: To observe the changes in pelvic balance after posterior reduction of balanced L5-S1 III-grade isthmic spondylolisthesis in adults. METHODS: A total of 18 adult patients with balanced L5-S1 III-grade isthmic spondylolisthesis were retrospectively studied after successful treatment by posterior decompression, reduction and L5-S1 interbody fusion in Department of Orthopedic Surgery, the First Affiliated Hospital of Soochow University from October 2009 to October 2014.L5-S1 of eight patients were fixed with pedical strews, while others were fixed upgrade to L4.Spino-pelvic parameters: slipping percentage (SP), spondy slip angle (SSA), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT) and lumbar lordosis (LL) were measured on standing lateral view radiograms.The changes in pelvic balance were analyzed after posterior reduction. RESULTS: All the patients experienced significant changes in SP and SSA with (42.4%+/-8.3)% and (9.8+/-4.9) degrees improved significantly while no significant differences were recorded in PI, PT, SS and LL. PI, PT, SS and LL passed from an average(61.1+/-6.2) degrees , (16.2+/-4.5) degrees , (44.8+/-2.9) degrees , (51.3+/-9.3) degrees preoperatively to (61.4+/-6.1) degrees , (14.9+/-4.0) degrees , (46.5+/-3.0) degrees , (48.6+/-7.0) degrees respectively.According to K means cluster analysis, pelvic balance improved postoperatively.No significant correlation was found for DeltaPT, DeltaSS with DeltaSP, while DeltaPT and DeltaSS had a significant correlation with DeltaSSA (correlation coefficient 0.77 and 0.82 respectively). CONCLUSION: Posterior SSA reduction in adults with balanced L5-S1 III-grade isthmic spondylolisthesis can improve the former pelvic balance. PMID- 27356788 TI - [Risk factors of postoperative major complication after spine deformity surgery]. AB - OBJECTIVE: To analyze risk factors of major complications after spinal deformity surgery. METHODS: From January 2011 to December 2014, 254 consecutive patients undergone spinal deformity surgery , 68 male and 186 female, average age 22.1(3 73) years, were divided into two groups based on if they had major complications after surgery.Univariate and multivariate analysis (Logistic regression) were used to identify the risk factors. RESULTS: Among them, 29 patients had major complications after surgery.Univariate risk factors showed that medical history, scoliosis operation history, preoperative nerve injury, vertebral number of major curve, cobb of major curve, Kyphosis(>90 degrees ), time of operation, operative bleeding and osteotomy of group I were higher or longer than those of group II.Maximal voluntary ventilation (MVC) and orthopaedic rate of group I were worse than those of group II[(63.5%+/-23.9%)vs(76.7%+/-21.9%), (53%+/-23%) vs(68%+/ 21%), P<0.05]. Logistic regression identified that preoperative nerve injury(OR=5.976), medical history>10 years (OR=4.095), MVC observed/predicted<50(OR=7.405), time of operation>5 h (OR=3.510), osteotomy(OR=3.472)were final risk factors for major complications. CONCLUSIONS: Major complications after surgery to treat spinal deformity can be predicted through preoperative nerve injury, medical history, maximal voluntary ventilation observed/predicted, time of operation and osteotomy during the surgery.The patients with these risk factors need more preoperative care and postoperative care to reduce the occurrence of major complications. PMID- 27356789 TI - [Research of the effect of bone mineral density and fracture site of the vertebrae on low back pain in elderly patients with osteoporotic vertebral compression fractures]. AB - OBJECTIVE: To investigate the effect of bone mineral density(BMD) and fracture site of the vertebrae on low back pain in elderly patients with osteoporotic vertebral compression fractures. METHODS: From August 2011 to August 2013, a total of 107 senile patients with osteoporotic vertebral compression fractures underwent percutaneous vertebroplasty were followed up for more than 2 ( average 2.5) years in Department of orthopedics, Xuanwu Hospital, Capital Medical University. The incidence of low back pain after vertebroplasty were analyzed on visual analog scale (VAS), and the relationship between BMD, vertebral fracture site were investigated. RESULTS: A total of 18 cases(16.8%)after vertebroplasty have significant low back pain. Along with BMD decreased [(-2.90+/-0.91) vs ( 4.87+/-0.52)], the VAS of low back pain increasing, which showed statistical significance difference[(-3.12+/-0.91) vs (4.03+/-1.08), P<0.05]. The site of vertebral fracture was lower, the VAS was higher. CONCLUSIONS: About 16.8% patients show obvious low back pain after vertebroplasty. BMD and Vertebral fracture site were important factors of low back pain in elderly patients with osteoporotic vertebral compression fractures after vertebroplasty. PMID- 27356790 TI - [A novel self-growing rod technique for early onset scoliosis: an experimental study based on a porcine scoliosis model]. AB - OBJECTIVE: To evaluate the efficacy of a growth-guidance growing rod in an established porcine scoliosis model via the Cobb angle correction and the continued spinal growth. METHODS: Immature pigs (age: 6 weeks old, weight: 6-8 kg) were instrumented and tethered using a three separate incisions fashion.After considerable scoliosis was induced, the pigs were randomly assigned to an experiment group (EG) and a sham group (SG). In EG, the growing rod was implanted and the pigs were euthanized 8 weeks postoperatively; while in SG, the whole instrumentations were only removed and the pigs were followed up over a 8-week period.Dorsoventral (DV) X-ray radiographs were taken prior to and immediately after the growing rod implanting surgery, and at 4-week intervals to assess the Cobb angle orrection and instrumentation positioning.The continued spinal growth and the rod sliding were also assessed from the radiographs. RESULTS: Of the 16 pigs, one pig encountered infection during the inducement of the experimental scoliosis and thus was excluded from analysis.Of the remaining 15 pigs, all animals developed progressive, structural scoliosis.The 15 pigs were randomized into EG(n=10) and SG(n=5). Two pigs in EG encountered infection and were also excluded from analysis.Of the remaining 8 pigs in EG, no neurologic complications, implant failure or infection were observed.In EG, the Cobb angle of the scoliosis before the growing rod implanted was (52.1 +/-14.1) degrees and it decreased to (25.4+/-15.2) degrees postoperatively.After 8 weeks, the Cobb angle was (20.2+/-11.4) degrees .In SG, the Cobb angle of the scoliosis after 8 week tethering period was (55.2+/-15.7) degrees and it decreased to (53.6+/ 15.8) degrees after removal of the tethering.The curvature remained stable (51.2 degrees ) during the subsequent 8 weeks.During the 8-16th week, the spinal height increased 14.2 cm and radiographic analysis of the growing rod sliding revealed an average distraction of 39.8 mm in EG; while in SG, the increased spinal height was 14.9 cm.The difference of the increased spinal height between EG and SG was not significant (P=0.821). CONCLUSION: The novel growing rod system can provide substantial correction of deformity, and additionally, allow for continually spinal growth without significant growing disturbance. PMID- 27356791 TI - [Effect of standardized treatment on reactivity of toe microcirculation in patients with type 2 diabetes mellitus]. AB - OBJECTIVE: To evaluate the effect of standardized treatment on reactivity of the lower limb terminal microcirculation in patients with type 2 diabetes mellitus (T2DM) by high frequency ultrasound combined with warm bath. METHODS: A total of 66 patients with T2DM were collected from June 2014 to May 2015 in the Second Affiliated Hospital of Wenzhou Medical University.According to the vascular complications , the patients were divided into group A without complications (36 cases)and group B with complications (30 cases). Hemodynamic parameters such as peak systolic velocity(PSV), end-diastolic velocity(EDV) and resistance index(RI) of the right plantar digital artery on fibular side of the 1st toe were acquired through Doppler in all subjects.Then the above operation were performed repetitively on all subjects after the right foot was immersed in 40 C warm water for 5 minutes.The change rates of PSV, EDV and RI were calculated after warm bath.All subjects were examined again after three months treatment .The growth rates of the change rate of PSV, EDV and RI were calculated after treatment.All parameters were analyzed. RESULTS: The change rates of the parameters in group B before and after treatment were lower than those of group A, before treatment (0.108+/-0.077 vs 0.184+/-0.091, P=0.037, 0.184+/-0.101 vs 0.380+/-0.167, P=0.002, 0.007+/-0.004 vs 0.015+/-0.008, P=0.028 7), after treatment (0.155+/ 0.111 vs 0.421+/-0.138, 0.287+/-0.108 vs 0.794+/-0.286, 0.012+/-0.008 vs 0.039+/ 0.014, P=0.000); the post treatment growth rates of the change rates of the parameters in group B were all less than those of group A (0.414+/-0.303 vs 2.192+/-2.673, P=0.048, 0.660+/-0.406 vs 1.422+/-1.075, P=0.042, 0.633+/-0.830 vs 2.191+/-2.269, P=0.048). The change rates of the parameters in two groups after treatment were higher than those before treatment (all P<0.05). CONCLUSION: Warm bath test can be used to detect change degree of hemodynamic parameters in patients with T2DM so as to evaluate reactivity of blood microcirculation, which has a certain clinical application value in treatment. PMID- 27356792 TI - [Study of the effects of three luteal phase supporting strategies on clinical outcomes of intrauterine insemination]. AB - OBJECTIVE: To explore the effects of three luteal phase supporting strategies on clinical outcomes of intrauterine insemination (IUI). METHODS: 1 779 subjects who underwent IUI at the Center of Reproductive Medicine, Peking University Third Hospital from November 2014 to June 2015 were enrolled in this retrospectively study.According to the luteal phase supporting strategies, all the subjects were divided into three groups: subjects receiving Dydrogesterone were group A; subjects receiving oral micronized progesterone were group B; subjects receiving vaginal micronized progesterone were group C. The pregnancy outcomes, including clinical pregnancy rate, early miscarriage rate, biochemical pregnancy rate and ectopic pregnancy rate were compared in the three groups. RESULTS: There was no significant difference in the three groups in constituent ratio, average IUI times, rate of the natural cycle, rate ofovulation cycle and dropout rate(P>0.05). Similarly, there was also no significant difference in pregnancy outcomes in all groups.Subsequent stratified analysis demonstrated that pregnancy outcomes in subjects of natural cycle and ovulation cycle still showed no significant difference(P>0.05). CONCLUSION: Our study suggested that the effects of three luteal phase supporting strategies on clinical outcomes of IUI were similar.The medication in clinic should be individualized. PMID- 27356793 TI - [Value of cerebrovascular hemodynamics analysis on diagnosis of cerebral microcirculation disorder]. AB - OBJECTIVE: To determine the clinical value of cerebrovascular hemodynamics analysis (CVA) on cerebral microcirculation. METHODS: One hundred consecutive patients from neurological department of Peking University People's Hospital from April to October, 2015, with symptoms of dizziness, lightheadedness, headache etc., who were diagnosed with ischemic cerebrovascular disease with normal transcranial doppler (TCD) and abnormal CVA, were recruited in this study.Other medical conditions were excluded through clinic and imaging examinations among these patients.Patients were categorized into mild, moderate and severe subgroups based on the degrees of decreased blood flow velocity and/or volume, and received treatment accordingly.CVA parameters including the minimum flow velocity (Vmin), the minimum flow volume (Qmin), peripheral resistance (R), critical pressure (CCP) and dynamic resistance (CVR) etc.before and after treatment were compared statistically (t test). RESULTS: Out of the 100 patients with abnormal CVA, 52 patients had bilateral changes and 48 patients had unilateral changes.The minimum flow velocity and the minimum flow volume anomalies were found in 100 and 92 cases, respectively.A total of 47, 32 and 21 patients had mild, moderate and severe abnormal changes, respectively.Out of the 63 patients who had follow-up CVA after treatment (drop-out 37 cases), there were 63 abnormal Vmin cases, 60 abnormal Qmin cases, 17 abnormal R cases, 18 abnormal CCP cases, 41 abnormal characteristic impedance (Zc) cases, 41 abnormal elastic wave velocity (Wv) cases, 23 abnormal vascular compliance (C) cases, all before treatment.After treatment, symptoms and Vmin synchronization improved in 61 cases (96.8%), Qmin improved in 58 cases (96.6%), R improved in 13 cases (76.5%), CCP improved in 10 cases (55.6%), Zc improved in 27 cases (65.8%), Wv improved in 25 cases (61.0%), C improved in 6 cases (26.1%). All improvements were statistically significant (P<0.05), with Vmin, Qmin, R and CCP showing most significant changes (P<0.000 1). The CVR treatment showed no significant before and after treatment (P>0.05). CONCLUSIONS: CVA is an important method in assessing cerebral microcirculation perfusion, providing information on intracranial microvascular bed that cannot be detected by TCD.It is not only helpful for diagnosis, but also evaluable for monitoring clinical treatment of cerebral microcirculation disorder.CVA is also helpful in determining the location of cerebral circulation impairment by correlation with carotid ultrasound and TCD. PMID- 27356794 TI - [Endovascular implantation of iodine-125 seeds strand and portal vein stenting followed by transcatheter arterial chemoembolization combined therapy with sorafenib for hepatocellular carcinoma with main portal vein tumor thrombus]. AB - OBJECTIVE: To compare the therapeutic effect of portal vein stenting and endovascular implantation of iodine-125 seeds strand followed by transcatheter arterial chemoembolization combined with or without sorafenib in patients for hepatocellular carcinoma (HCC) with main portal vein tumor thrombus (MPVTT). METHODS: A total of 53 patients with HCC complicated by MPVTT who received portal vein stenting and endovascular implantation of iodine-125 seeds strand followed by transcatheter arterial chemoembolization combined without (group A, n=38) or with (group B, n=15) sorafenib in Affiliated Yancheng Hospital of Southeast University Medical College during January 2010 and August 2015 were analyzed retropectively.Overal survival, progress free survival and procedure-related adverse event were compared between the two groups. RESULTS: The technical success rate was 100% for placement of (125)I seeds strand and stent in the obstructed main portal vein.No serious procedure-related adverse events occurred. Median survival time of group A and B were 12.1 and 14.8 months, respectively (P=0.037). Additionally, Median progress free survival time of group A and B were 2.8 and 4.0 months, respectively (P=0.002). CONCLUSIONS: Endovascular implantation of iodine-125 seeds strand and portal vein stenting followed by transcatheter arterial chemoembolization combined with sorafenib could improve the survival time, the progress free survival time of patients with HCC complicated by MPVTT. PMID- 27356795 TI - [Clinical analysis of 23 gynecologic carcinoma patients with brain metastasis]. AB - OBJECTIVE: To explore the clinicopathological characteristics and treatments of brain metastasis (BM) in patients with gynecologic carcinoma. METHODS: Twenty three pathologically confirmed patients with gynecologic carcinoma who had brain metastasis between February 2008 and October 2012 were analyzed retrospectively. RESULTS: The primary carcinoma was cervical cancer in 5 patients, endometrial carcinoma in 8 patients and ovarian cancer in 10 patients, which accounted for 1.81% (5/276), 2.10% (8/380) and 2.67% (10/374) of patient with the same diagnosis of the same period, respectively.Among them, 91.3% (21/23) patients had heterochronous BM.Single BM was documented in 52.2% (12/23) patients.Besides, 78.2% (18/23) BM located in cerebrum.At the time of BM, 91.3% (21/23) patients had symptoms of central nervous system, in which headache ranked the top (90.4%). Altogether, thirteen patients had extracranial metastasis, in which 9 of them had metastasis of the lung.The median post-brain-metastasis survival (mPBMS) for the recursive partitioning analysis (RPA) classes I-III was 54 months, 9 months and 1 month, respectively (P<0.01). None of surgery, radiotherapy or chemotherapy treatment was proven to have prognosis-improving ability either in single variant or multivariate analysis.However, in patients with extracranial metastasis, chemotherapy could significantly improve their mPBMS (P<0.05). CONCLUSIONS: The incidence of brain metastasis in patients with cervical cancer, endometrial carcinoma, and ovarian cancer increased gradually.RPA was valuable for a prognostic assessment in gynecologic carcinoma patients with BM.Chemotherapy could significantly improve prognosis of gynecologic carcinoma patients with BM if extracranial metastasis was presented. PMID- 27356796 TI - [The relationship between group B streptococcus genital infection and premature rupture of membrane]. AB - OBJECTIVE: To investigate the relationship between the group B streptococcal (GBS) genital infection of the pregnant women and premature rupture of membrane (PROM). METHODS: Five hundred and eighty seven cases in our hospital maternity clinic or hospital delivery of pregnant women were enrolled from October 2014 to December 2014, including 189 cases of pregnant women with PROM as the observation group and 398 cases of pregnant women without PROM as a control group.GBS in their rectum and vagina secretion was separated and tested by using Group B Streptococcus Chromogenic Agar. RESULTS: Fifty eight cases were detected GBS positive in all 587 pregnant women.The positive rate was 9.9%.In 189 cases of PROM, 37 cases were GBS positive and the positive rate was 19.6%.While in 398 cases of normal pregnant women, 21 cases were positive and the positive rate was 5.3%.The difference has statistically significant (P<0.01). CONCLUSION: GBS infection may be a risk factor for the occurrence of PROM.Psychological counseling, health education and antibiotics should be applied to the GBS positive pregnant women as a preventive strategy. PMID- 27356797 TI - [Brain plastic alterations in subjects with chronic right-sided sensorineural hearing loss: a resting-state MRI study]. AB - OBJECTIVE: To investigate the nodal properties and reorganization of whole-brain functional network in subjects with severe right-sided SNHL. METHODS: From June 2012 to June 2013, a total of 19 patients with severe right-sided SNHL were collected from Zhongda Hospital or the recruitment advertising along with 31 healthy controls.Based on the graph-theoretical analysis, the whole-brain functional networks were constructed using the BOLD-fMRI data of all subjects.Two sample two-tailed t-tests were used to investigate the differences between two groups in nodal metrics, such as node degree, node betweenness, node global efficiency and node local efficiency.All metrics were corrected by multiple comparisons.Partial correlation analysis was used to estimate the relationship between the significant metrics and the duration or severity of hearing loss. RESULTS: The right-sided SNHL showed significantly increased betweenness centrality in left supramarginal gyrus and right fusiform.However, other nodal parameters showed no statistical difference.Besides, patients exhibited no significant association between the altered metrics and clinical variables. CONCLUSION: Alterations of local topological properties may underlie cerebral cross-modal plastic reorganization in visual or speech-related regions in severe right-sided SNHL patients. PMID- 27356798 TI - [Utility of texture analysis of magnetic resonance imaging in differential diagnosis of common pediatric cerebellar tumors in children]. AB - OBJECTIVE: To analyze magnetic resonance images of the posterior cranial fossa tumors, and evaluate the texture characteristics of three kinds of children's posterior cranial fossa tumors by support vector machine (SVM). METHODS: From May 2008 to August 2015, a total of 76 patients with children's posterior cranial fossa tumors in First Affiliated Hospital of Zhengzhou University were retrospectively analyzed, texture analysis was performed on the three types of tumors. RESULTS: The 5 texture parameters extracted from the gray level co occurrence matrix had at least 3 parameters which had statistically significant difference between the two different classes of data sets (P<0.05). For all kinds of data sets, the variance parameters of gray value of ROI region had statistically significant differences.The accuracy rate of SVM test in the remarkable difference of the ependymomas and medulloblastomas, the ependymomas and astrocytomas and the medulloblastomas and astrocytomas was 86.15%+/-4.16%, 73.63%+/-5.82% and 74.32%+/-5.85%, respectively. CONCLUSION: The analysis of texture features can provide more quantitative information which could provide a new thought and method for the differential diagnosis of tumors in the posterior cranial fossa. PMID- 27356799 TI - [Surgical treatment of ventriculoperitoneal shunt guided by ultrasound to the patients with idiopathic intracranial hypertension]. AB - OBJECTIVE: To investigate the clinical efficacy of ventriculoperitoneal shunt treatment to patients with idiopathic intracranial hypertension. METHODS: The clinical data of 32 patients with idiopathic intracranial hypertension who were admitted to Henan Provincial People's Hospital from August 2011 to February 2014 were collected.The underlying diseases included occlusion of the superior sagittal sinus (2 cases) and occlusion of transverse sinus (2 cases), and all 4 cases had a history of chronic otitis media.Twenty eight cases, with a history of oral contraceptive drugs (2 cases) and unclear etiology (26 cases), had normal venous sinus confirmed by imaging examination.All of 32 patients underwent ventriculoperitoneal shunt. RESULTS: The symptoms of 32 patients such as headache, nausea, and vomiting were relieved obviously after surgery.The symptom of visual impairment of 31 cases got better in varying degrees except that 1 case went blind before operation.Besides 2 cases of loss of follow-up, the remaining 30 cases were followed up for 2 years.Thirty cases had no perioperative infection.One case had infection 1 year after operation.No one had the shunt tube blockage. CONCLUSIONS: Patients with idiopathic intracranial hypertension should be taken active surgical treatment when drug therapy fails and could obtain satisfactory clinical curative effect by accepting treatment of ventriculoperitoneal shunt.By intraoperative ultrasound guiding lateral ventricle puncture can be achieved accurately. PMID- 27356800 TI - [Effect of SIRT1 deficiency on function of brown adipose tissue in obese mice]. AB - OBJECTIVE: To investigate the effect of silent mating type information regulation 2 homolog 1 (SIRT1) deficiency on function of brown adipose tissue (BAT) in high fat diet (HFD)-induced obese mice. METHODS: Male SIRT1 deficient heterozygous (SIRT1(+ /-)) mice and their wild-type (WT) littermates were challenged with a HFD diet for 16 weeks to induce obesity model.Energy metabolic cages were used to measure oxygen consumption and heat production, and cold tolerance test was to evaluate the adaptive thermogenic function.With brown fat collected after the diet intervention, determination techniques were adopted included HE staining for morphologic changes, immunohistochemical staining and Western blotting for uncoupling protein 1 (UCP1) expression, quantitative real-time PCR for relative content of mitochondria DNA (mtDNA). RESULTS: Compared to WT controls, SIRT1(+ / ) mice displayed significant decreases in both oxygen consumption and heat production[(2 681+/-297) vs (3 017+/-313) ml.kg(-1).h(-1,) (19.05+/-2.40) vs (21.15+/-2.49) kcal.kg(-1).h(-1,) both P<0.05)], as well as an impairment in maintaining their body temperature during the cold challenge.HE staining revealed the accumulation of larger lipid droplets in BAT of SIRT1(+ /-) mice, and both immunohistochemical staining and Western blotting indicated an obvious reduction in expression of UCP1 (P<0.05). Quantitative real-time PCR showed a significant decrease in the relative mtDNA content in BAT of SIRT1(+ /-) mice (0.38+/-0.10 vs 1.00+/-0.40, P<0.05). CONCLUSION: SIRT1 deficiency promotes BAT dysfunction, meaning that whitening in obese mice. PMID- 27356801 TI - [Percutaneous coronary intervention in eastern urban China: 2001-2011]. AB - OBJECTIVE: We aimed to assess trends in clinical characteristics, treatment, and outcomes for hospitalized patients undergoing percutaneous coronary intervention (PCI) in eastern urban China from 2001 to 2011. METHOD: We analyzed a Chinese eastern representative sample of hospital admissions for PCI identified in China PEACE-retrospective CathPCI study using a two-stage random sampling design and calculated the weighted data of clinical information in each year. RESULTS: We included 3 308 admissions for PCI in 29 urban hospitals.Between 2001 and 2011, rates of hospitalizations for PCI increased by 15 fold.Compared with 2001, the patients undergoing PCI were more likely to be female, older than 70 years, and to have history of diabetes, hypertension, dyslipidemia and PCI in 2011.The proportion of trans radial PCIs was increased from 3.5% in 2001 to 72.6% in 2011 (Statistic=-28.95, Ptrend<0.000 1); the proportion of drug eluting stents (DES) among all the implanted stents was increased from 18.2%in 2001 to 98.4% in 2011(Statistic=-40.82, Ptrend<0.000 1), largely due to increased use of domestic DES.Less than 10% of medical records of patients undergoing primary PCI documented door time and balloon time.The median length of stay decreased from 13 days in 2001 to 10 days in 2011 (Statistic=-0.11, Ptrend<0.001). In-hospital mortality did not change significantly, but both any bleeding (Statistic= 2.66, Ptrend< 0.01) and access bleeding were decreased significantly (Statistic= 5.55, Ptrend< 0.000 1). CONCLUSIONS: During 2001 and 2011 in eastern urban China, there has been a rapid increase in the number and significant change in treatment patterns of PCI.Quality gaps are identified that represent opportunities to improve care. PMID- 27356802 TI - [Cross-sectional study of differential effects with age on non-invasive central hemodynamics and peripheral arterial stiffness of healthy people in Beijing communities]. AB - OBJECTIVE: To observe the variation of central hemodynamics and peripheral arterial stiffness in different ages and to investigate the parameters of differential effects in younger individuals (<=60y) and older individuals (>60y). METHODS: We conducted a population-based cross-sectional study in eight regions by random cluster sampling, from April to July 2014 in Beijing, China.Central hemodynamics and peripheral arterial stiffness parameters were determined in 861 healthy (372 male), normotensive individuals, aged 20 to 91(56+/-14) years.The main observed indexes were central systolic blood pressure (cSBP), arterial augmentation index (AI), augmentation pressure (AP), heart-ankle pulse wave velocity (haPWV) and brachial-ankle PWV (baPWV). Subjects were divided into six groups by 10 aged segment.Differences between groups and age tendency were observed. RESULTS: The mean values of cSBP, AI, AP, haPWV and baPWV were (113+/ 12) mmHg, (90+/-18)%, (-5+/-9) mmHg, (987+/-144) cm/s and (1 382+/-254) cm/s, respectively.cSBP, AI, AP, haPWV and baPWV increased with age (P<0.001). In average, cSBP, baPWV and haPWV increased 3 mmHg, 97 cm/s and 62 cm/s by additional 10 years, respectively.cSBP, AI and AP increased slowly after 60 years old, while haPWV and baPWV increased significantly with age (P<0.001). Stepwise regression analysis showed: cSBP was mainly relevant with mean arterial pressure(b=0.990, P<0.001), while baPWV and haPWV were relevant with age(b=8.858, 5.971; P<0.001). AI and AP were associated with height and rest heart rate (b= 0.676, -0.660 and b=-0.361, -0.341, P<0.001). Individuals were divided into two groups by age 60.The age-related changes in AI were significant in under 60-year old; while the changes in baPWV were more prominent in over 60-year-old.However there was no significant difference in cSBP between two groups. CONCLUSIONS: In healthy people, there are obvious differences of age tendency in central hemodynamics and peripheral arterial stiffness parameters.AI might be a good predictor of cardiovascular disease for early stage, especially for early coronary artery disease. PMID- 27356803 TI - BH3-only protein Bim predicts advanced stage of cutaneous melanoma. AB - BACKGROUND: Bim having strong pro-apoptotic effects belongs to the BH3-only proteins of the Bcl-2 protein family and contributes to survival pathways in cancer cells. OBJECTIVES: We aimed to investigate Bim protein expression in cutaneous melanoma (CM). METHODS: Bim protein expression was assessed by immunohistochemistry in primary and metastatic melanomas and correlated with clinical and histopathological features. RESULTS: The Bim immunoreactivity score of the primary melanomas investigated (4.6 +/- 1.5) was significantly (P < 0.0001) higher than that observed in metastases (2.8 +/- 1.1). Low Bim expression was significantly associated with primary nodular melanoma type (P = 0.005). Moreover, Bim expression was significantly inversely correlated with tumour thickness (r = -0.36; P = 0.0035), advanced stage of disease (stage III and IV; r = -0.60; P < 0.0001), disease relapse (r = -0.18; P = 0.034) and disease-related death (r = -0.19; P = 0.026). Advanced stage of disease was independently predicted by low Bim expression (P = 0.0010, odds ratio: 0.22, 95% CI: 0.10-0.56) on multivariate analysis; however, Bim was not shown to be an independent predictor for disease relapse (P = 0.40) and disease-related death (P = 0.77). CONCLUSIONS: Our data demonstrate that Bim protein expression is significantly inversely correlated with melanoma features that are associated with worse prognosis. We have shown that Bim protein expression in CM is an independent predictor for advanced disease confirming that this pro-apoptotic BH3-only protein might be a potent biomarker and promising therapeutic target. PMID- 27356804 TI - Using acupressure to minimize discomforts during pregnancy. AB - OBJECTIVE: To describe responses issued by pregnant women, and the improvement of the gravidic discomforts after the use of the acupressure technique. METHOD: Qualitative and descriptive study conducted with 15 pregnant women between November 2013 and February 2014 in a Basic Health Unit in Natal, RN, Brazil. The data were collected through unstructured interviews and depositions that were then transcribed and treated according to Minayo's operative proposal, carefully read, compared and organized into two groups. RESULTS: The categories that resulted were: Positive effects of acupressure, and the recommended use of acupressure. According to pregnant women, the discomforts of pregnancy cramps, fatigue in the legs, lower back pain and headaches decreased with the use of acupressure. CONCLUSIONS: Based on the results, acupressure should be introduced by the nurse in pre-natal care as a therapeutic resource for the pregnant woman's well-being. PMID- 27356805 TI - Women's experience with contraception from the perspective of gender. AB - OBJECTIVE: To analyse the experience of women with contraception from the perspective of gender. METHODS: Qualitative and exploratory-descriptive study conducted at three basic healthcare units in the city of Lagoa Seca - PB, Brazil, with 15 women interviewed between January and May 2013. The content analysis technique was used to process the data. RESULTS: Data analysis led to the core category 'women's contraceptive choices and their relationship with gender dynamics', that subsequently led to the subcategories 'unequal construction of gender identities in childhood and adolescence', 'outcome of gender dynamics in (contra)ception during adolescence', and ' medicalisation of the female body'. CONCLUSIONS: It was observed that the experience with contraception is related to the dynamics of gender, with the outcome of teenage pregnancy and the medicalization of the body. PMID- 27356806 TI - Building a digital application for teaching vital signs. AB - OBJECTIVE: To describe the steps in creating a digital application directed to teaching vital signs for nursing students. METHOD: This is a methodological study, conducted from March to October 2014, in which have followed the stages of analysis, design and development of technological tool, based on the theoretical framework of Galvis-Panqueva. We conducted a narrative review of the literature on the subject, and then picked up the best platform for application hosting. RESULTS: Once the steps proposed in the theoretical framework were followed, the analysis outlined the content and technological infrastructure. As for the design, it provided the assessment of the environment and its interface and operation, and finally the development materialized the projection of the design and interactive features proposed in previous steps. CONCLUSION: The application is an interactive support in the training of nursing students, and it is suggested that validation of content be performed for further practical application. PMID- 27356807 TI - Nursing languages as an international communication vehicle for nurses. PMID- 27356808 TI - Repetitive Periodic Atrial Oversensing in a Cardiac Implantable Electrical Defibrillator at 35 Minutes and 50 Minutes Past the Hour: What Is the Diagnosis? PMID- 27356809 TI - Multicentre cohort study 'Rehabilitation of Occupational Skin Diseases - Optimization and Quality Assurance of Inpatient Management (ROQ)': results from a 3-year follow-up. AB - BACKGROUND: A tertiary individual prevention programme (TIP) is offered to patients with severe occupational skin disease (OSD) in Germany. Previously, it was shown that the burden of OSDs is considerably reduced in patients up to 1 year after the TIP. OBJECTIVES: To evaluate the long-term effects of the TIP. PATIENTS AND METHODS: In a prospective multicentre cohort study, the clinical and patient-reported outcome data 3 years after the TIP were evaluated. RESULTS: Of the 1788 patients initially included in the study, 1410 were available for the 3 year follow-up analysis. The severity of OSD, the use of topical corticosteroids and days of absence from work were significantly reduced 3 years after the TIP, and the quality of life and skin protective behaviour were significantly improved. Of the patients, 96.9% were able to resume work. One thousand one hundred and sixty-six patients (82.7%) were still working 3 years after the TIP, 874 of them (75.0%) in the same occupational field. Hairdressers had the lowest rate of remaining in their original profession (41.3%). CONCLUSIONS: The follow up during 3 years of this unique cohort of patients with OSDs shows that the TIP is associated with sustained improvements in terms of disease severity, ability to work, quality of life, and prognosis. PMID- 27356810 TI - Similarity of symptoms between transient epileptic amnesia and Lewy body disease. AB - Epilepsy with the main symptom of amnesia is known as transient epileptic amnesia (TEA). Dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia. The concept that Lewy body disease includes Parkinson's disease with dementia and dementia with Lewy bodies was proposed in the 2005 revision of the Clinical Diagnostic Criteria. Here, we describe a woman with cognitive impairment, olfactory dysfunction, and reduced 123 I-meta iodobenzylguanidine uptake on myocardial scintigraphy. The patient and her family and friends were unaware of parkinsonism, visual hallucinations, or epilepsy for a long period. After syncope occurred twice within a short interval, electroencephalography revealed sharp waves from the bilateral frontal to parietal lobes, indicating a diagnosis of TEA. The present case prompted us to compare the symptoms of TEA with the clinical diagnostic criteria for dementia with Lewy bodies, revealing their similarities. We also discuss whether Lewy body disease may cause TEA rather than having an incidental association with it. PMID- 27356811 TI - An Unusual Complication of Nasojejunal Tube Placement: Jejunal Perforation. PMID- 27356812 TI - An Unusual Case of Colonic Intussusception Masquerading as a Transverse Colon Mass. PMID- 27356813 TI - Mantle Cell Lymphoma of the Gastrointestinal Tract in a Patient with Renal Cell Carcinoma. PMID- 27356814 TI - False Aneurysm of the Common Hepatic Artery Ruptured Into the Duodenum. PMID- 27356815 TI - Ulcerative Colitis Presenting With Palmoplantar Neutrophilic Dermatosis. PMID- 27356816 TI - Abdominal Cocoon: Primary Sclerosing Encapsulating Peritonitis. PMID- 27356817 TI - Acute Presentation of a Mucinous Adenocarcinoma of the Appendix. PMID- 27356818 TI - An Unusual Rectal Lesion in a Homosexual Man. PMID- 27356819 TI - Successful Endoscopic Ultrasound-Guided Coil Embolization For Severe Duodenal Bleeding. PMID- 27356820 TI - Editorial: Reflux While Running: Something to Belch About. AB - Running is the most popular form of exercise in the United States. Gastroesophageal reflux (GER) is common during exercise and may affect performance. Previous studies have focused on increased intra-abdominal pressure as a major determinant of acid reflux during physical exertion. In this issue, Herregods et al. examined the mechanisms of GER in healthy volunteers using simultaneous high-resolution manometry and pH impedance testing performed while running. Novel observations afforded by the utilization of state-of-the-art technology include the importance of transient lower esophageal sphincter relaxation ("belch reflex") and transient formation of hiatal hernia during exercise. The findings are provocative and lend credence to commonsense strategies to minimize the consequences of belching in runners. PMID- 27356823 TI - Editorial: Magnetic Resonance Elastography and Non-Alcoholic Fatty Liver Disease: Time for an Upgrade? AB - Elastography techniques, such as two-dimensional magnetic resonance elastography (2D-MRE) are increasingly used for the non-invasive assessment of liver fibrosis in patients with nonalchoholic fatty liver disease (NAFLD). Loomba et al. demonstrate that 3D-MRE (shear wave frequency 40 Hz) had even greater diagnostic accuracy than the commercially available 2D-MRE (shear wave frequency 60 Hz) in diagnosing advanced fibrosis (area under the receiver operator curve, AUROC 0.981 vs. 0.921, P<0. 05) using liver biopsy as reference standard. Despite limitations, MRE serves as an important tool in risk stratification for patients with NAFLD. PMID- 27356826 TI - Response to Kaakoush et al. PMID- 27356827 TI - Reduction in Gut Microbial Diversity as a Mechanism of Action of Exclusive Enteral Nutrition. PMID- 27356828 TI - Position Change in Colonoscopy-A Turn for the Better? PMID- 27356829 TI - Reply to Kaif et al. PMID- 27356830 TI - Tricyclic Antidepressants: What to Choose and Which Dose? PMID- 27356831 TI - Response to Keszthelyi et al. PMID- 27356832 TI - Tryciclic Antidepressants in Refractory GERD: Poorly Effective Drugs or Wrong Patients? PMID- 27356834 TI - Response to Savarino et al. PMID- 27356833 TI - Hepatocellular Carcinoma With Peliosis-Like Change-Mimicking Hemangioma: A LI RADS Exception. PMID- 27356835 TI - Familial Adenomatous Polyposis; Succesful Use of Sirolimus. PMID- 27356836 TI - Outpatient Terlipressin Infusion for the Treatment of Refractory Ascites. PMID- 27356837 TI - Liver Disease in Pregnancy: Beyond the Guidelines. PMID- 27356838 TI - Severity of Systemic Inflammatory Response Syndrome Affects Outcomes in Decompensated Cirrhotics with Spontaneous Bacterial Peritonitis. PMID- 27356839 TI - Watch Your Speed-A Traumatic Case of Budd-Chiari Syndrome. PMID- 27356842 TI - Corrigendum: ACG Clinical Guideline: Diagnosis and Management of Barrett's Esophagus. PMID- 27356843 TI - Corrigendum: Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir With or Without Ribavirin in HCV-Infected Patients Taking Concomitant Acid-Reducing Agents. PMID- 27356844 TI - Corrigendum: Isolated Duodenal Varices Without Cirrhosis. PMID- 27356845 TI - Corrigendum: Anaphylaxis to Milk After Elimination Diet for Eosinophilic Gastrointestinal Disease. PMID- 27356846 TI - Low colectomy rate five years after diagnosis of ulcerative colitis. Results from a prospective population-based cohort in Sweden (ICURE) diagnosed during 2005 2009. AB - OBJECTIVE: The medical treatment of ulcerative colitis (UC) has seen a change towards a more active attitude during recent years, including both the use of more traditional drugs as well as new biological substances. In this epidemiological study we have evaluated the results of modern treatment of UC in a population-based cohort of patients including all age groups, with regard to relapse rate, colectomy and IBD-associated mortality. MATERIAL AND METHODS: Patients diagnosed with UC in the Uppsala health care region in the middle of Sweden during 2005-2009 were included in the study. Out of 524 patients, 491 (93%) could be followed for five full years or until death. RESULTS: Nineteen patients (3.9%) had died and two of these deaths could be attributed to UC (one postoperative death and one colonic carcinoma). The following drugs were used by the patients during the study period: 5-ASA (91%), systemic steroids (66%), immunomodulators (IMM), mainly thiopurines (26%) and anti-TNF (11%). During the observation period, 74% experienced at least one relapse and 5.3% were subjected to colectomy. Among patients <17 years at diagnosis, colectomy was performed in two (4.8%). CONCLUSIONS: Five years after diagnosis of ulcerative colitis, 5.3% had been subjected to colectomy and two patients (0.38%) had died because of the disease. PMID- 27356847 TI - Height gain after two-years-of-age is associated with better cognitive capacity, measured with Raven's coloured matrices at 15-years-of-age in Malawi. AB - Stunting is a measure of chronic undernutrition, and it affects approximately 160 million children worldwide. Cognitive development of stunted children is compromised, but evidence about the association between height gain in late childhood and adolescent cognitive capacity is scarce. We aimed to determine the association between height gains at different ages, including late childhood, and cognitive capacity at 15-years-of-age. We conducted a prospective cohort study in a rural African setting in Southern Malawi. The study cohort was enrolled between June 1995 and August 1996. It originally comprised mothers of 813 fetuses, and the number of children born live was 767. These children were followed up until the age of 15 years. The anthropometrics were measured at one and 24-months-of age and 15-years-of-age, and cognitive capacity of participants was assessed at 15-years-of-age with Raven's Coloured Matrices score, mathematic test score, median reaction time (RT) (milliseconds) and RT lapses. The associations between growth and the outcome measures were assessed with linear regression. Raven's Coloured Matrices score was predicted by height gain between 24 months and 15 years-of-age (coefficient 0.85, P = 0.03) and (coefficient 0.69, P = 0.06), but not by earlier growth, when possible confounders were included in the model. The association weakened when school education was further added in the model (coefficient = 0.69, P = 0,060). In conclusion, in rural Malawi, better growth in late childhood is likely to lead to better cognitive capacity in adolescence, partly through more school education. In light of these results, growth promotion should not only be limited to early childhood. PMID- 27356849 TI - A Synthesis of (+/-)-Aplydactone. AB - Aplydactone is an unusual brominated sesquiterpenoid isolated from the sea hare Aplysia dactylomela. Its highly strained skeleton contains two four- and three six-membered rings and features three adjacent quaternary carbon atoms. Although it is most likely of photochemical origin, attempts to generate it from a chamigrane precursor have failed thus far. In this work, we present a total synthesis of aplydactone that relies on two photochemical key steps that are not biomimetic but highly effective in establishing the two cyclobutane rings. Our synthesis also features an unusual Barbier-type cyclization and culminates in new radical conditions to install the sterically hindered secondary bromide of the natural product. PMID- 27356848 TI - Triazole resistance in Aspergillus fumigatus isolates from patients with cystic fibrosis in Italy. AB - BACKGROUND: Aspergillus fumigatus is frequently recovered from respiratory secretions of cystic fibrosis (CF) patients. Azole resistance has been increasingly reported. OBJECTIVES: To assess the prevalence of azole resistance in A. fumigatus isolates from patients followed by two CF centers of northern Italy. METHODS: 423 isolates (220 patients) were screened for azole resistance. Resistance was confirmed with the EUCAST method and cyp51A gene sequencing. Microsatellite genotyping was performed and results were compared with those of environmental resistant isolates. RESULTS: No resistance was detected in one center, while 8.2% of the patients of the other center harbored resistant isolates. The TR34/L98H alteration in the cyp51A gene, present in seven cases, resulted associated with poor in-vitro activity of all tested azoles. CONCLUSIONS: The environmental origin of the resistance seems to be probable since azole resistance was found also in naive patients and an identical microsatellite genotype in clinical and environmental isolates was observed. PMID- 27356850 TI - Lessons learnt on biases and uncertainties in personal exposure measurement surveys of radiofrequency electromagnetic fields with exposimeters. AB - Personal exposure measurements of radio frequency electromagnetic fields are important for epidemiological studies and developing prediction models. Minimizing biases and uncertainties and handling spatial and temporal variability are important aspects of these measurements. This paper reviews the lessons learnt from testing the different types of exposimeters and from personal exposure measurement surveys performed between 2005 and 2015. Applying them will improve the comparability and ranking of exposure levels for different microenvironments, activities or (groups of) people, such that epidemiological studies are better capable of finding potential weak correlations with health effects. Over 20 papers have been published on how to prevent biases and minimize uncertainties due to: mechanical errors; design of hardware and software filters; anisotropy; and influence of the body. A number of biases can be corrected for by determining multiplicative correction factors. In addition a good protocol on how to wear the exposimeter, a sufficiently small sampling interval and sufficiently long measurement duration will minimize biases. Corrections to biases are possible for: non-detects through detection limit, erroneous manufacturer calibration and temporal drift. Corrections not deemed necessary, because no significant biases have been observed, are: linearity in response and resolution. Corrections difficult to perform after measurements are for: modulation/duty cycle sensitivity; out of band response aka cross talk; temperature and humidity sensitivity. Corrections not possible to perform after measurements are for: multiple signals detection in one band; flatness of response within a frequency band; anisotropy to waves of different elevation angle. An analysis of 20 microenvironmental surveys showed that early studies using exposimeters with logarithmic detectors, overestimated exposure to signals with bursts, such as in uplink signals from mobile phones and WiFi appliances. Further, the possible corrections for biases have not been fully applied. The main findings are that if the biases are not corrected for, the actual exposure will on average be underestimated. PMID- 27356851 TI - Mechanism of uncoupling protein 2-mediated myocardial injury in hypothermic preserved rat hearts. AB - In the present study, the alterations in uncoupling protein 2 (UCP2) expression following hypothermic preservation in rat hearts were investigated. Isolated rat hearts were preserved in Celsior solution for 3-12 h followed by 60 min of reperfusion. The cardiac function was evaluated using the Langendorff perfusion system. UCP2 and silent mating type information regulation 2 homolog 1 (SIRT1) proteins were detected by western blot analysis. The ATP production and mitochondrial reactive oxygen species (ROS) levels were assessed. Subsequent to preservation in ice-cold Celsior solution for 3-12 h, the UCP2 protein expression in rat hearts was observed to increase in a time-dependent manner. The UCP2 inhibitor genipin inhibited the hypothermic preservation-induced cardiac dysfunction, prevented a decline in ATP production induced by 9 h of preservation, however had no effect on the hypothermic preservation-induced increase in mitochondrial ROS levels. Compared with the control group, the SIRT1 protein expression in rat hearts reduced following hypothermic preservation. Compared with the 9-h preservation group, Celsior solution supplemented with the SIRT1 activator resveratrol (20 or 40 umol/l) inhibited UCP2 protein overexpression, prevented the decline in ATP production and resulted in an improvement cardiac function. The SIRT1 inhibitor EX-527 abolished the resveratrol-induced inhibition of UCP2 overexpression and cardiac protection in the hypothermic preserved rat heart. These observations suggest that downregulation of UCP2 expression in the hypothermic preserved rat heart in part initiated the protective mechanism via the SIRT1 pathway. PMID- 27356852 TI - In Depth Proteome Analysis of Ripening Muscadine Grape Berry cv. Carlos Reveals Proteins Associated with Flavor and Aroma Compounds. AB - Ripening in nonclimacteric fruits such as grape involves complex chemical changes that have a profound influence on the accumulation of flavor and aroma compounds distinct to a particular grape genotype. In this study, proteome characterization of wine type bronze muscadine grape (Vitis rotundifolia cv. Carlos), primarily grown in the Southeastern United States was performed during berry ripening. Stage-specific protein expression was obtained among different stages of berries. Differential analysis showed the expression of 522 proteins that regulate diverse biological processes and metabolic pathways. Of these, 30 proteins are associated with the production of key phenolic compounds, whereas 25 are associated with the production of muscadine aroma compounds. These proteins are involved in the phenylpropanoid pathway, terpene synthesis, fatty acid derived volatiles and esters that affect muscadine berry flavor and aroma characteristics. Further, gene expression analysis during ripening validated the expression pattern of 12 proteins. Catechin, epicatechin, and four stilbenes were quantified to correlate observed proteome changes. This study not only revealed biochemical changes during muscadine berry ripening but also offers indicators for marker-assisted breeding to enhance organoleptic properties of muscadine grape to improve its flavor and aroma properties. PMID- 27356853 TI - Interventions to tackle malnutrition and its risk factors in children living in slums: a scoping review. AB - CONTEXT: Children living in slums are at high risk of being malnourished. There are no published reviews on existing interventions promoting better nutrition for children living in slums and the risk factors for children's malnutrition. Improved understanding of the risk factors for malnutrition in slums communities and the impact of interventions on children's health can provide guidance to practitioners and decision-makers. The present review is designed to provide this information. METHODS: The search included 30 electronic bibliographic databases and relevant eligible studies published up to December 2013. RESULTS: The search located 1512 citations. Full text relevance screening was conducted on 226 studies and on abstracts for 16 studies. The final 58 unique studies included 22 on interventions and 38 on risk. All of the interventions were nutrition specific, with nutritional intervention being the most dominant type. Seventy three per cent of the interventions were assessed effective. CONCLUSION: The findings stressed the gaps in knowledge in terms of quality assessment and programmatic recommendations to identify children who are the most at risk of malnutrition to appropriately target interventions. Finally, the review helped to inform a systematic review (Cochrane Systematic review protocol 2015) that will examine the impact of interventions on outcome measures. PMID- 27356854 TI - Rapid In Vitro Evaluation of Antiretroviral Barrier to Resistance at Therapeutic Drug Levels. AB - Failure of combination antiretroviral (ARV) therapy in HIV-infected patients is often associated with the emergence of drug resistance-associated mutations (RAMs). To facilitate analysis of the barrier to resistance at therapeutically relevant ARV concentrations, we performed fixed-dose in vitro HIV-1 drug resistance selection assays using the immortalized MT-2 T-cell line and primary human CD4+ T cells with a panel of FDA-approved ARVs, each at their respective cell culture equivalent clinical trough concentration (CCE Cmin). At high multiples of its CCE Cmin, emtricitabine (FTC) selected for the rapid emergence of M184I/V, a result consistent with resistance emergence in vivo. While the rate of viral breakthrough in the presence of rilpivirine or efavirenz was delayed relative to FTC, both inhibitors selected for virus with known clinically relevant RAMs. No viral breakthrough was observed for the protease inhibitor atazanavir even at subtherapeutic drug concentrations, which is consistent with its previously characterized high in vivo barrier to resistance. Depending on assay conditions, treatment with integrase inhibitors elvitegravir and raltegravir resulted in breakthrough of both resistant and wild-type virus. The RAMs observed in drug selections were not detected above a 2% threshold by deep sequencing in the in vitro virus inoculum, and only rarely in isolates from treatment-naive HIV+ patients. These new viral breakthrough assays facilitate the analysis of multiple experimental replicates and conditions in parallel and provide a rapid quantitative means to evaluate drug resistance emergence at therapeutically relevant drug concentrations, which should facilitate the identification of new ARVs with a high barrier to resistance. PMID- 27356855 TI - A new in vivo analysis model to detect sexually dimorphic rat liver cytochrome P450 gene expression dependent on growth hormone secretory patterns. AB - Several drug-metabolizing cytochrome P450 (CYP) enzymes exhibit sexual dimorphism depending on the pituitary growth hormone (GH) secretory patterns. However, the mechanism underlying CYP sexual dimorphism remains unclear. We previously established a transgenic (Alb-DsRed2 Tg) rat that expressed red fluorescent DsRed2 protein, particularly in hepatocytes, to visualize cell differentiation and multiplication and found that hepatic DsRed2 expression exhibited sexual dimorphism that was limited to adult males. In this study, we compared the expression patterns between sexual dimorphic Cyps and DsRed2 in Tg rats after experimentally reversing the GH secretory patterns in males and females. Postnatal day 1 male and female Tg rats were gonadectomized and then testosterone propionate (0.25 mg/rat) was subcutaneously administered to ovariectomized females immediately after surgery. Cyp mRNA and DsRed2 expression levels were quantified using RT-PCR and an in vivo imaging system, respectively. GH-dependent Cyps and hepatic DsRed2 expression patterns were reversed in males and females at 9 weeks after birth and were significantly correlated (P<0.05). This suggested that DsRed2 expression in these Tg rats depended on GH secretory patterns. Based on DsRed2 fluorescence, this Tg rat model could become a tool to readily and effectively evaluate changes in GH-dependent Cyp expression. PMID- 27356856 TI - In situ hybridization study of CYP2D mRNA in the common marmoset brain. AB - The common marmoset is a non-human primate that has increasingly employed in the biomedical research including the fields of neuroscience and behavioral studies. Cytochrome P450 (CYP) 2D has been speculated to be involved in psycho-neurologic actions in the human brain. In the present study, to clarify the role of CYP2D in the marmoset brain, we investigated the expression patterns of CYP2D mRNA in the brain using in situ hybridization (ISH). In addition, to identify the gene location of CYP2D19, a well-studied CYP2D isoform in the common marmoset, a fluorescence in situ hybridization (FISH) study was performed. Consistent with findings for the human brain, CYP2D mRNA was localized in the neuronal cells of different brain regions; e.g., the cerebral cortex, hippocampus, substantia nigra, and cerebellum. FISH analysis showed that the CYP2D19 gene was located on chromosome 1q, which is homologous to human chromosome 22 on which the CYP2D6 gene exists. These results suggest that CYP2D in the marmoset brain may play the same role as human CYP2D6 in terms of brain actions, and that the CYP2D19 gene is conserved in a syntenic manner. Taken together, these findings suggest that the common marmoset is a useful model for studying psychiatric disorders related to CYP2D dysfunction in the brain. PMID- 27356858 TI - Synthesis of sulfonamides via copper-catalyzed oxidative C-N bond cleavage of tertiary amines. AB - A copper-catalyzed coupling reaction of sulfonyl chlorides with tertiary amines via the oxidative C-N bond cleavage of tertiary amines was developed. Sulfonamides were synthesized using this strategy in moderate to good yields. The reaction was applicable to various tertiary amines, as well as sulfonyl chlorides. PMID- 27356857 TI - Extended Anatomical Grading in Diffuse Axonal Injury Using MRI: Hemorrhagic Lesions in the Substantia Nigra and Mesencephalic Tegmentum Indicate Poor Long Term Outcome. AB - Clinical outcome after traumatic diffuse axonal injury (DAI) is difficult to predict. In this study, three magnetic resonance imaging (MRI) sequences were used to quantify the anatomical distribution of lesions, to grade DAI according to the Adams grading system, and to evaluate the value of lesion localization in combination with clinical prognostic factors to improve outcome prediction. Thirty patients (mean 31.2 years +/-14.3 standard deviation) with severe DAI (Glasgow Motor Score [GMS] <6) examined with MRI within 1 week post-injury were included. Diffusion-weighted (DW), T2*-weighted gradient echo and susceptibility weighted (SWI) sequences were used. Extended Glasgow outcome score was assessed after 6 months. Number of DW lesions in the thalamus, basal ganglia, and internal capsule and number of SWI lesions in the mesencephalon correlated significantly with outcome in univariate analysis. Age, GMS at admission, GMS at discharge, and low proportion of good monitoring time with cerebral perfusion pressure <60 mm Hg correlated significantly with outcome in univariate analysis. Multivariate analysis revealed an independent relation with poor outcome for age (p = 0.005) and lesions in the mesencephalic region corresponding to substantia nigra and tegmentum on SWI (p = 0.008). We conclude that higher age and lesions in substantia nigra and mesencephalic tegmentum indicate poor long-term outcome in DAI. We propose an extended MRI classification system based on four stages (stage I-hemispheric lesions, stage II-corpus callosum lesions, stage III-brainstem lesions, and stage IV-substantia nigra or mesencephalic tegmentum lesions); all are subdivided by age (>=/<30 years). PMID- 27356859 TI - Risk factors related to aggressive condylar resorption after orthognathic surgery for females: retrospective study. AB - OBJECTIVE: The aim of the present study was to identify the risk factors for aggressive condylar resorption (ACR) after orthognathic surgery. METHODS: A total of 25 female patients with osteoarthritis (OA) scheduled for orthognathic surgery were divided into two groups: those who exhibited ACR (ACR (+), n = 8) and those who did not exhibit ACR (ACR (-), n = 17) after surgery. Clinical indices were used to determine the extent of mandibular advancement, the presence of temporomandibular disorder (TMD), and relevant medical treatment histories (including the use of oral contraceptive (OC) medication. TMJ dysfunction was clinically evaluated in terms of pain, the presence of sounds (clicks or crepitus), and disc displacement, joint effusion (JE), and synovial hyperplasia (SH); these were further investigated with the aid of magnetic resonance imaging (MRI). The cephalographic findings were compared with the normal profiles of Japanese subjects. RESULTS: The mean (with SD) extent of mandibular advancement was 11.4 mm (2.4) in ACR (+) and 4.1 mm (1.8) in ACR (-). The TMD medical history of ACR (+) was much more extensive than that of ACR (-); all patients in ACR (+) had a history of OC use. More patients in ACR (+) than in ACR (-) had TMJ dysfunction and disc displacement, JE, and SH on MRI. Preoperative cephalograms showed that ACR (+) patients exhibited counterclockwise rotation of the mandible and retrognathism that was attributable to a small sella-nasion-B (SNB) angle, a wide mandibular plane angle, and a negative inclination of the ramus. CONCLUSIONS: The present findings suggest that the development of ACR after orthognathic surgery to treat mandibular retrognathism may be associated with coexisting TMJ pathologic abnormality. PMID- 27356860 TI - Selenium nanoparticles as a nutritional supplement. AB - Selenium is an essential trace element in the diet, required for maintenance of health and growth; however, its toxicity could cause serious damage depending on dose and chemical form. Selenium nanoparticles (SeNPs) represent what we believe to be a novel prospect for nutritional supplementation because of their lower toxicity and ability to gradually release selenium after ingestion. In this review, we discuss various forms and types of SeNPs, as well as the way they are synthesized. We also discuss absorption and bioavailability of nanoparticles within the organism. SeNPs demonstrate anticancer and antimicrobial properties that may contribute to human health, not only as dietary supplements, but also as therapeutic agents. PMID- 27356861 TI - A population-based study for 30-d hospital readmissions after acute ischemic stroke. AB - OBJECTIVE: To determine post-stroke 30-d readmission rate, its predictors, its impact on mortality and to identify potentially preventable causes of post-stroke 30-d readmission in a population-based study. PATIENTS AND METHODS: We identified all acute ischemic strokes (AIS) using the International Classification of Diseases 9th revision codes (433.x1, 434.xx and 436) via the Rochester Epidemiology Project (REP) between January 2007 and December 2011. Acute stroke care in Olmsted County is provided by two medical centers, Saint Marys Hospital and Olmsted Medical Center Hospital. All readmissions to these two hospitals were accounted for this study. Thirty-day readmission data was abstracted through manual chart review. The REP linkage database was used to identify the status (living/dead) of all patients at last follow up. RESULTS: Forty-one (7.6%, 95% CI 5.7%-10.2%) of total 537 AIS patients were readmitted 30-d post-stroke. In a multivariable logistic regression model, discharge to nursing home following index stroke (OR: 0.29, 95% CI 0.08-0.84) was an independent negative predictor of unplanned 30-d readmission. In a subgroup of patients with dementia, being married at time of index stroke was found to be a negative predictor of readmission (OR: 0.10, 95% CI 0.005-0.58). Only 2.8% of the patients had potentially preventable readmissions. Hospital readmission had no significant impact on patient's short-term (three months) or long-term (one or two years) mortality (p > 0.05). CONCLUSION: Post-stroke 30-d readmission rate is low in AIS patients from Olmsted County. Further research is needed in regarding discharge checklists, protocols and stroke transitional programs to reduce potentially preventable readmissions. PMID- 27356862 TI - Analysis of the effect of adjuvant radiotherapy on outcomes and complications after radical hysterectomy in FIGO stage IB1 cervical cancer patients with intermediate risk factors (GOTIC Study). AB - BACKGROUND: There are no definitive criteria for identifying which patients with The International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical cancer will benefit from adjuvant therapy after radical hysterectomy. The aims of this study were to clarify the efficacy of adjuvant therapy and assess complications after radical hysterectomy in patients with FIGO stage IB1 cervical cancer with intermediate risk factors. METHODS: Between January 2005 and December 2009, the medical records of 75 stage IB1 patients' intermediate risk factors (i.e., tumor size 2-4 cm, lymphovascular involvement, and/or deep stromal invasion >1/2) who underwent radical hysterectomy at six institutions were collected, and these patients were enrolled in this nonrandomized retrospective study. We simplified the criteria of intermediate risk factors as much as possible, as the criteria adopted in some clinical studies are complicated in practice. RESULTS: The patients were grouped according to the receipt of adjuvant therapy as follows: 46 patients, no further treatment; 19 patients, external beam radiation treatment, including 9 patients who received brachytherapy; 5 patients, concurrent chemoradiotherapy (CCRT); and 5 patients, chemotherapy (CT). The clinical outcomes and complications in each group were analyzed. After an average follow-up of 82.6 months (range, 24-135 months), only one patient with all three risk factors who received radiotherapy (RT) experienced recurrence. Excluding this patient, the remaining patients who received RT, CCRT, or CT had two or three risk factors. Lymphedema was significantly more common among patients who received RT or CCRT, whereas the incidence of ileus and ureteral obstruction was not different among the treatment groups. However, an unsutured peritoneum increased the risk of ileus. CONCLUSIONS: The findings of this study suggest that RT and CCRT after radical hysterectomy are not beneficial in patients with intermediate risk factors. In particular, RT and CCRT appeared to increase the incidence of lymphedema. A prospective randomized study is needed to verify the findings of this study. PMID- 27356863 TI - Health care seeking behaviours in pregnancy in rural Sindh, Pakistan: a qualitative study. AB - BACKGROUND: Pakistan has alarmingly high numbers of maternal mortality along with suboptimal care-seeking behaviour. It is essential to identify the barriers and facilitators that women and families encounter, when deciding to seek maternal care services. This study aimed to understand health-seeking patterns of pregnant women in rural Sindh, Pakistan. METHODS: A qualitative study was undertaken in rural Sindh, Pakistan as part of a large multi-country study in 2012. Thirty three focus group discussions and 26 in-depth interviews were conducted with mothers [n = 173], male decision-makers [n = 64], Lady Health Workers [n = 64], Lady Health Supervisors [n = 10], Women Medical Officers [n = 9] and Traditional Birth Attendants [n = 7] in the study communities. A set of a priori themes regarding care-seeking during pregnancy and its complications as well as additional themes as they emerged from the data were used for analysis. Qualitative analysis was done using NVivo version 10. RESULTS: Women stated they usually visited health facilities if they experienced pregnancy complications or danger signs, such as heavy bleeding or headache. Findings revealed the importance of husbands and mothers-in-law as decision makers regarding health care utilization. Participants expressed that poor availability of transport, financial constraints and the unavailability of chaperones were important barriers to seeking care. In addition, private facilities were often preferred due to the perceived superior quality of services. CONCLUSION: Maternal care utilization was influenced by social, economic and cultural factors in rural Pakistani communities. The perceived poor quality care at public hospitals was a significant barrier for many women in accessing health services. If maternal lives are to be saved, policy makers need to develop processes to overcome these barriers and ensure easily accessible high-quality care for women in rural communities. TRIAL REGISTRATION: NCT01911494. PMID- 27356865 TI - Spatial aromatic fences of metal-organic frameworks for manipulating the electron spin of a fulleropyrrolidine nitroxide radical. AB - The electron spin properties of a fulleropyrrolidine nitroxide radical incarcerated in the pores of MOF-177 and MIL-53 respectively were investigated for the first time. It was found that the spatial confinement effect and intramolecular interactions in these two solid-state spin systems lead to dramatically distinctive spin dynamics. PMID- 27356864 TI - Negative selection maintains transcription factor binding motifs in human cancer. AB - BACKGROUND: Somatic mutations in cancer cells affect various genomic elements disrupting important cell functions. In particular, mutations in DNA binding sites recognized by transcription factors can alter regulator binding affinities and, consequently, expression of target genes. A number of promoter mutations have been linked with an increased risk of cancer. Cancer somatic mutations in binding sites of selected transcription factors have been found under positive selection. However, action and significance of negative selection in non-coding regions remain controversial. RESULTS: Here we present analysis of transcription factor binding motifs co-localized with non-coding variants. To avoid statistical bias we account for mutation signatures of different cancer types. For many transcription factors, including multiple members of FOX, HOX, and NR families, we show that human cancers accumulate fewer mutations than expected by chance that increase or decrease affinity of predicted binding sites. Such stability of binding motifs is even more exhibited in DNase accessible regions. CONCLUSIONS: Our data demonstrate negative selection against binding sites alterations and suggest that such selection pressure protects cancer cells from rewiring of regulatory circuits. Further analysis of transcription factors with conserved binding motifs can reveal cell regulatory pathways crucial for the survivability of various human cancers. PMID- 27356866 TI - Self-discharge of electrochemical capacitors based on soluble or grafted quinone. AB - The self-discharge of hybrid electrochemical capacitors based on the redox activity of electrolyte additives or grafted species to the electrode material is investigated simultaneously for the cell and each individual electrode. Electrochemical capacitors using a redox-active electrolyte consisting in hydroquinone added to the electrolyte solution and a redox-active electrode based on anthraquinone-grafted carbon as a negative electrode are investigated. The results are analyzed by using Conway kinetic models and compared to those of a common electrochemical double layer capacitor. The self-discharge investigation is complemented by charge/discharge cycling and it is shown that processes affecting galvanostatic charge/discharge cycling and the self-discharge rate occurring at each electrode of an electrochemical capacitor are different but related to each other. The electrochemical capacitor containing hydroquinone in the electrolyte exhibits a much quicker self-discharge rate than that using a negative electrode based on grafted anthraquinone with a 50% decay of the cell voltage of the fully charged device in 0.6 and 6 h, respectively. The fast self discharge of the former is due to the diffusion of benzoquinone molecules (formed at the positive electrode during charging) to the negative electrode, where they are reduced, causing a quick depolarization. The grafting of anthraquinone molecules on the carbon material of the negative electrode led to a much slower self-discharge, which nonetheless occurred, by the reaction of the reduced form of the grafted species with electrolyte species. PMID- 27356867 TI - Why stay in a bad relationship? The effect of local host phenology on a generalist butterfly feeding on a low-ranked host. AB - BACKGROUND: In plant-feeding insects, the evolutionary retention of polyphagy remains puzzling. A better understanding of the relationship between these organisms and changes in the metabolome of their host plants is likely to suggest functional links between them, and may provide insights into how polyphagy is maintained. RESULTS: We investigated the phenological change of Cynoglossum officinale, and how a generalist butterfly species, Vanessa cardui, responded to this change. We used untargeted metabolite profiling to map plant seasonal changes in both primary and secondary metabolites. We compared these data to differences in larval performance on vegetative plants early and late in the season. We also performed two oviposition preference experiments to test females' ability to choose between plant developmental stages (vegetative and reproductive) early and late in the season. We found clear seasonal changes in plant primary and secondary metabolites that correlated with larval performance. The seasonal change in plant metabolome reflected changes in both nutrition and toxicity and resulted in zero survival in the late period. However, large differences among families in larval ability to feed on C. officinale suggest that there is genetic variation for performance on this host. Moreover, females accepted all plants for oviposition, and were not able to discriminate between plant developmental stages, in spite of the observed overall differences in metabolite profile potentially associated with differences in suitability as larval food. CONCLUSIONS: In V. cardui, migratory behavior, and thus larval feeding times, are not synchronized with plant phenology at the reproductive site. This lack of synchronization, coupled with the observed lack of discriminatory oviposition, obviously has potential fitness costs. However, this "opportunistic" behavior may as well function as a source of potential host plant evolution, promoting for example the acceptance of new plants. PMID- 27356869 TI - Enhanced selective adsorption of CO2 on nitrogen-doped porous carbon monoliths derived from IRMOF-3. AB - The N-doped porous carbon monoliths prepared by direct carbonization of IRMOF-3, through an in situ activation and self-templating process, were found to exhibit significantly enhanced performance for the selective adsorption of CO2 compared to pristine IRMOF-3. The transformation from the microporous structure to the meso-macroporous structure opens the pathway for CO2 to more easily access the nitrogen anchors. PMID- 27356868 TI - Angiogenin ameliorates corneal opacity and neovascularization via regulating immune response in corneal fibroblasts. AB - BACKGROUND: Angiogenin (ANG), a component of tears, is involved in the innate immune system and is related with inflammatory disease. We investigated whether ANG has an immune modulatory function in human corneal fibroblasts (HCFs). METHODS: HCFs were cultured from excised corneal tissues. The gene or protein expression levels of interleukin (IL)-1beta (beta), IL-4, IL-6, IL-8, IL-10, complements, toll-like receptor (TLR)4, myeloid differentiation primary response gene (MYD)88, TANK-binding kinase (TBK)1, IkappaB kinase-epsilon (IKK-epsilon) and nuclear factor-kappaB (NF-kappaB) were analyzed with or without ANG treatment in tumor necrosis factor-alpha (TNF-alpha)- or lipopolysaccharide (LPS)-induced inflammatory HCFs by real-time polymerase chain reaction (PCR), Western blotting and immunocytochemistry. Inflammatory cytokine profiles with or without ANG were evaluated through immunodot blot analysis in inflammatory HCFs. Corneal neovascularization and opacity in a rat model of corneal alkali burn were evaluated after application of ANG eye drops. RESULTS: ANG decreased the mRNA levels of IL-1beta, IL-6, IL-8, TNF-alpha receptor (TNFR)1, 2, TLR4, MYD88, and complement components except for C1r and C1s and elevated the mRNA expression of IL-4 and IL-10. Increased signal intensity of IL-6, IL-8 and monocyte chemotactic protein (MCP)-1 and MCP-2 induced by TNF-alpha or LPS was weakened by ANG treatment. ANG reduced the protein levels of IKK-epsilon by either TNF-alpha and LPS, and decreased TBK1 production induced by TNF-alpha, but not induced by LPS. The expression of NF-kappaB in the nuclei was decreased after ANG treatment. ANG application lowered corneal neovascularization and opacity in rats compared to controls. CONCLUSION: These results demonstrate that ANG reduces the inflammatory response induced by TNF-alpha or LPS in HCFs through common suppression of IKK epsilon-mediated activation of NF-kappaB. This may support the targeting of immune-mediated corneal inflammation by using ANG. PMID- 27356870 TI - Individuality in nutritional preferences: a multi-level approach in field crickets. AB - Selection may favour individuals of the same population to differ consistently in nutritional preference, for example, because optimal diets covary with morphology or personality. We provided Southern field crickets (Gryllus bimaculatus) with two synthetic food sources (carbohydrates and proteins) and quantified repeatedly how much of each macronutrient was consumed by each individual. We then quantified (i) whether individuals were repeatable in carbohydrate and protein intake rate, (ii) whether an individual's average daily intake of carbohydrates was correlated with its average daily intake of protein, and (iii) whether short term changes in intake of carbohydrates coincided with changes in intake of protein within individuals. Intake rates were individually repeatable for both macronutrients. However, individuals differed in their relative daily intake of carbohydrates versus proteins (i.e., 'nutritional preference'). By contrast, total consumption varied plastically as a function of body weight within individuals. Body weight-but not personality (i.e., aggression, exploration behaviour)-positively predicted nutritional preference at the individual level as large crickets repeatedly consumed a higher carbohydrate to protein ratio compared to small ones. Our finding of level-specific associations between the consumption of distinct nutritional components demonstrates the merit of applying multivariate and multi-level viewpoints to the study of nutritional preference. PMID- 27356873 TI - Retracted: Nontraumatic Lesions of the Clavicle in a Paediatric Population: Incidence and Management. AB - [This retracts the article DOI: 10.1155/2014/261952.]. PMID- 27356872 TI - Human-animal chimeras: ethical issues about farming chimeric animals bearing human organs. AB - Recent advances in stem cells and gene engineering have paved the way for the generation of interspecies chimeras, such as animals bearing an organ from another species. The production of a rat pancreas by a mouse has demonstrated the feasibility of this approach. The next step will be the generation of larger chimeric animals, such as pigs bearing human organs. Because of the dramatic organ shortage for transplantation, the medical needs for such a transgressive practice are indisputable. However, there are serious technical barriers and complex ethical issues that must be discussed and solved before producing human organs in animals. The main ethical issues are the risks of consciousness and of human features in the chimeric animal due to a too high contribution of human cells to the brain, in the first case, or for instance to limbs, in the second. Another critical point concerns the production of human gametes by such chimeric animals. These worst-case scenarios are obviously unacceptable and must be strictly monitored by careful risk assessment, and, if necessary, technically prevented. The public must be associated with this ethical debate. Scientists and physicians have a critical role in explaining the medical needs, the advantages and limits of this potential medical procedure, and the ethical boundaries that must not be trespassed. If these prerequisites are met, acceptance of such a new, borderline medical procedure may prevail, as happened before for in-vitro fertilization or preimplantation genetic diagnosis. PMID- 27356871 TI - Acetylated tau destabilizes the cytoskeleton in the axon initial segment and is mislocalized to the somatodendritic compartment. AB - BACKGROUND: Neurons are highly polarized cells in which asymmetric axonal dendritic distribution of proteins is crucial for neuronal function. Loss of polarized distribution of the axonal protein tau is an early sign of Alzheimer's disease (AD) and other neurodegenerative disorders. The cytoskeletal network in the axon initial segment (AIS) forms a barrier between the axon and the somatodentritic compartment, contributing to axonal retention of tau. Although perturbation of the AIS cytoskeleton has been implicated in neurological disorders, the molecular triggers and functional consequence of AIS perturbation are incompletely understood. RESULTS: Here we report that tau acetylation and consequent destabilization of the AIS cytoskeleton promote the somatodendritic mislocalization of tau. AIS cytoskeletal proteins, including ankyrin G and betaIV spectrin, were downregulated in AD brains and negatively correlated with an increase in tau acetylated at K274 and K281. AIS proteins were also diminished in transgenic mice expressing tauK274/281Q, a tau mutant that mimics K274 and K281 acetylation. In primary neuronal cultures, the tauK274/281Q mutant caused hyperdynamic microtubules (MTs) in the AIS, shown by live-imaging of MT mobility and fluorescence recovery after photobleaching. Using photoconvertible tau constructs, we found that axonal tauK274/281Q was missorted into the somatodendritic compartment. Stabilizing MTs with epothilone D to restore the cytoskeletal barrier in the AIS prevented tau mislocalization in primary neuronal cultures. CONCLUSIONS: Together, these findings demonstrate that tau acetylation contributes to the pathogenesis of neurodegenerative disease by compromising the cytoskeletal sorting machinery in the AIS. PMID- 27356875 TI - Precision medicine in cardiology. AB - The cardiovascular research and clinical communities are ideally positioned to address the epidemic of noncommunicable causes of death, as well as advance our understanding of human health and disease, through the development and implementation of precision medicine. New tools will be needed for describing the cardiovascular health status of individuals and populations, including 'omic' data, exposome and social determinants of health, the microbiome, behaviours and motivations, patient-generated data, and the array of data in electronic medical records. Cardiovascular specialists can build on their experience and use precision medicine to facilitate discovery science and improve the efficiency of clinical research, with the goal of providing more precise information to improve the health of individuals and populations. Overcoming the barriers to implementing precision medicine will require addressing a range of technical and sociopolitical issues. Health care under precision medicine will become a more integrated, dynamic system, in which patients are no longer a passive entity on whom measurements are made, but instead are central stakeholders who contribute data and participate actively in shared decision-making. Many traditionally defined diseases have common mechanisms; therefore, elimination of a siloed approach to medicine will ultimately pave the path to the creation of a universal precision medicine environment. PMID- 27356874 TI - Intrinsic protein disorder in histone lysine methylation. AB - Histone lysine methyltransferases (HKMTs), catalyze mono-, di- and trimethylation of lysine residues, resulting in a regulatory pattern that controls gene expression. Their involvement in many different cellular processes and diseases makes HKMTs an intensively studied protein group, but scientific interest so far has been concentrated mostly on their catalytic domains. In this work we set out to analyze the structural heterogeneity of human HKMTs and found that many contain long intrinsically disordered regions (IDRs) that are conserved through vertebrate species. Our predictions show that these IDRs contain several linear motifs and conserved putative binding sites that harbor cancer-related SNPs. Although there are only limited data available in the literature, some of the predicted binding regions overlap with interacting segments identified experimentally. The importance of a disordered binding site is illustrated through the example of the ternary complex between MLL1, menin and LEDGF/p75. Our suggestion is that intrinsic protein disorder plays an as yet unrecognized role in epigenetic regulation, which needs to be further elucidated through structural and functional studies aimed specifically at the disordered regions of HKMTs. REVIEWERS: This article was reviewed by Arne Elofsson and Piotr Zielenkiewicz. PMID- 27356876 TI - Biomarkers: Sensitivity of troponins for diagnosis and risk prediction. PMID- 27356878 TI - Climate change and the loss of organic archaeological deposits in the Arctic. AB - The Arctic is warming twice as fast as the global average with overlooked consequences for the preservation of the rich cultural and environmental records that have been stored for millennia in archaeological deposits. In this article, we investigate the oxic degradation of different types of organic archaeological deposits located in different climatic zones in West and South Greenland. The rate of degradation is investigated based on measurements of O2 consumption, CO2 production and heat production at different temperatures and water contents. Overall, there is good consistency between the three methods. However, at one site the, O2 consumption is markedly higher than the CO2 production, highlighting the importance of combining several measures when assessing the vulnerability of organic deposits. The archaeological deposits are highly vulnerable to degradation regardless of age, depositional and environmental conditions. Degradation rates of the deposits are more sensitive to increasing temperatures than natural soils and the process is accompanied by a high microbial heat production that correlates significantly with their total carbon content. We conclude that organic archaeology in the Arctic is facing a critical challenge that requires international action. PMID- 27356877 TI - Management of refractory cardiogenic shock. AB - Cardiogenic shock is a life-threatening condition that occurs in response to reduced cardiac output in the presence of adequate intravascular volume and results in tissue hypoxia. Cardiogenic shock has several underlying aetiologies, with the most common being acute myocardial infarction (AMI). Refractory cardiogenic shock presents as persistent tissue hypoperfusion despite administration of adequate doses of two vasoactive medications and treatment of the underlying aetiology. Investigators of the SHOCK trial reported a long-term mortality benefit of emergency revascularization for shock complicating AMI. Since the publication of the SHOCK trial and subsequent guideline recommendations, the increase in community-based use of percutaneous coronary intervention for this condition has resulted in a significant decline in mortality. Despite these successes in the past 15 years, mortality still remains exceptionally high, particularly in patients with refractory cardiogenic shock. In this Review, we discuss the aetiology and pathophysiology of cardiogenic shock and summarize the data on the available therapeutics and their limitations. Although new mechanical circulatory support devices have been shown to improve haemodynamic variables in patients with shock complicating AMI, they did not improve clinical outcomes and are associated with high costs and complications. PMID- 27356879 TI - Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. AB - Epitranscriptome modifications are required for structure and function of RNA and defects in these pathways have been associated with human disease. Here we identify the RNA target for the previously uncharacterized 5-methylcytosine (m(5)C) methyltransferase NSun3 and link m(5)C RNA modifications with energy metabolism. Using whole-exome sequencing, we identified loss-of-function mutations in NSUN3 in a patient presenting with combined mitochondrial respiratory chain complex deficiency. Patient-derived fibroblasts exhibit severe defects in mitochondrial translation that can be rescued by exogenous expression of NSun3. We show that NSun3 is required for deposition of m(5)C at the anticodon loop in the mitochondrially encoded transfer RNA methionine (mt-tRNA(Met)). Further, we demonstrate that m(5)C deficiency in mt-tRNA(Met) results in the lack of 5-formylcytosine (f(5)C) at the same tRNA position. Our findings demonstrate that NSUN3 is necessary for efficient mitochondrial translation and reveal that f(5)C in human mitochondrial RNA is generated by oxidative processing of m(5)C. PMID- 27356880 TI - Multiple cone pathways are involved in photic regulation of retinal dopamine. AB - Dopamine is a key neurotransmitter in the retina and plays a central role in the light adaptive processes of the visual system. The sole source of retinal dopamine is dopaminergic amacrine cells (DACs). We and others have previously demonstrated that DACs are activated by rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) upon illumination. However, it is still not clear how each class of photosensitive cells generates light responses in DACs. We genetically isolated cone function in mice to specifically examine the cone-mediated responses of DACs and their neural pathways. In addition to the reported excitatory input to DACs from light-increment (ON) bipolar cells, we found that cones alternatively signal to DACs via a retrograde signalling pathway from ipRGCs. Cones also produce ON and light-decrement (OFF) inhibitory responses in DACs, which are mediated by other amacrine cells, likely driven by type 1 and type 2/3a OFF bipolar cells, respectively. Dye injections indicated that DACs had similar morphological profiles with or without ON/OFF inhibition. Our data demonstrate that cones utilize specific parallel excitatory and inhibitory circuits to modulate DAC activity and efficiently regulate dopamine release and the light-adaptive state of the retina. PMID- 27356881 TI - Proteome analysis of the Mycobacterium tuberculosis Beijing B0/W148 cluster. AB - Beijing B0/W148, a "successful" clone of Mycobacterium tuberculosis, is widespread in the Russian Federation and some countries of the former Soviet Union. Here, we used label-free gel-LC-MS/MS shotgun proteomics to discover features of Beijing B0/W148 strains that could explain their success. Qualitative and quantitative proteome analyses of Beijing B0/W148 strains allowed us to identify 1,868 proteins, including 266 that were differentially abundant compared with the control strain H37Rv. To predict the biological effects of the observed differences in protein abundances, we performed Gene Ontology analysis together with analysis of protein-DNA interactions using a gene regulatory network. Our results demonstrate that Beijing B0/W148 strains have increased levels of enzymes responsible for long-chain fatty acid biosynthesis, along with a coincident decrease in the abundance of proteins responsible for their degradation. Together with high levels of HsaA (Rv3570c) protein, involved in steroid degradation, these findings provide a possible explanation for the increased transmissibility of Beijing B0/W148 strains and their survival in host macrophages. Among other, we confirmed a very low level of the SseA (Rv3283) protein in Beijing B0/W148 characteristic for all "modern" Beijing strains, which could lead to increased DNA oxidative damage, accumulation of mutations, and potentially facilitate the development of drug resistance. PMID- 27356883 TI - High and novel genetic diversity of Francisella tularensis in Germany and indication of environmental persistence. AB - In Germany tularemia is a re-emerging zoonotic disease. Therefore, we investigated wild animals and environmental water samples for the presence and phylogenetic diversity of Francisella tularensis in the poorly studied Berlin/Brandenburg region. The phylogenomic analysis of three isolates from wild animals revealed three new subclades within the phylogenetic tree of F. tularensis [B.71 from a raccoon dog (Nyctereutes procyonoides); B.74 from a red fox (Vulpes vulpes), and B.75 from a Eurasian beaver (Castor fiber albicus)]. The results from histological, PCR, and genomic investigations on the dead beaver showed that the animal suffered from a systemic infection. Indications were found that the bacteria were released from the beaver carcass into the surrounding environment. We demonstrated unexpectedly high and novel phylogenetic diversity of F. tularensis in Germany and the fact that the bacteria persist in the environment for at least one climatic season. These findings support a broader host species diversity than previously known regarding Germany. Our data further support the assumption derived from previous serological studies of an underestimated frequency of occurrence of the pathogen in the environment and in wild animals. F. tularensis was isolated from animal species not previously reported as natural hosts in Germany. PMID- 27356882 TI - Human Organotypic Cultured Cardiac Slices: New Platform For High Throughput Preclinical Human Trials. AB - Translation of novel therapies from bench to bedside is hampered by profound disparities between animal and human genetics and physiology. The ability to test for efficacy and cardiotoxicity in a clinically relevant human model system would enable more rapid therapy development. We have developed a preclinical platform for validation of new therapies in human heart tissue using organotypic slices isolated from donor and end-stage failing hearts. A major advantage of the slices when compared with human iPS-derived cardiomyocytes is that native tissue architecture and extracellular matrix are preserved, thereby allowing investigation of multi-cellular physiology in normal or diseased myocardium. To validate this model, we used optical mapping of transmembrane potential and calcium transients. We found that normal human electrophysiology is preserved in slice preparations when compared with intact hearts, including slices obtained from the region of the sinus node. Physiology is maintained in slices during culture, enabling testing the acute and chronic effects of pharmacological, gene, cell, optogenetic, device, and other therapies. This methodology offers a powerful high-throughput platform for assessing the physiological response of the human heart to disease and novel putative therapies. PMID- 27356884 TI - Glaucocalyxin B induces apoptosis and autophagy in human cervical cancer cells. AB - Glaucocalyxin (Gln), an ent-kaurane diterpenoid isolated from the Chinese traditional medicine, Rabdosia japonica, represents a novel class of anticancer drugs. GlnA is one of the three major forms of Gln and has demonstrated potent anticancer effects in a variety of cancer types. GlnB has only one structural difference from GlnA, an acetylated hydroxyl group at C14. This acetyl group results in high liposolubility and may enhance the antitumor activity of ent kaurane diterpenoid GlnB. However, few studies have reported the role of GlnB in cancer. The present study investigated the effect of GlnB in cervical cancer proliferation and cell death. Treatment with GlnB inhibits the proliferation of HeLa and SiHa cervical cancer cell lines in a dose-dependent manner, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide assays. In addition, GlnB increases the apoptotic cell population of HeLa and SiHa cells, as determined by fluorescence-activated cell sorting analysis and enhanced poly (ADP ribose) polymerase 1 cleavage by western blotting. GlnB also induces increased light chain 3 II/I protein cleavage in both cells, indicating the induction of autophagy. Furthermore, GlnB treatment increased the expression of phosphatase and tensin homolog and decreased the expression of phosphorylated-protein kinase B (Akt) in HeLa and SiHa cells, as assessed by western blotting. Taken together, the present results demonstrated that GlnB inhibited the proliferation of human cervical cancer cells in vitro through the induction of apoptosis and autophagy, which may be mediated by the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt signaling pathway. PMID- 27356885 TI - Role of nucleation mechanism on the size dependent morphology of organic aerosol. AB - The origins of the size dependent morphology of organic aerosol are explored by probing the morphology of poly(ethylene glycol)-400/ammonium sulfate mixtures using cryogenic-transmission electron microscopy. Surprisingly, we observe a size dependence at some compositions, but not at others. Our results suggest that size dependence occurs due to an activated process. PMID- 27356887 TI - Minoxidil topical treatment may be more efficient if applied on damp scalp in comparison with dry scalp. AB - There is yet no consensus among prescribers whether minoxidil (MXD) formulations should be applied on wet/damp or dry scalp and no clear FDA guidelines on the matter. We hypothesized that the use of MXD on damp scalp may lead to higher drug penetration. First, because the drug diffusion and consequent deposition into the hair follicle may be favored when follicle cast is humid. Second, because humidity may also prevent drug crystallization and, therefore, maintain a higher thermodynamic activity for longer periods, which leads to increased penetration. Following in vitro experiments on rat and porcine skin we confirmed the hypothesis, which could markedly improve treatment effectiveness. PMID- 27356886 TI - Pretargeted PET Imaging Using a Site-Specifically Labeled Immunoconjugate. AB - In recent years, both site-specific bioconjugation techniques and bioorthogonal pretargeting strategies have emerged as exciting technologies with the potential to improve the safety and efficacy of antibody-based nuclear imaging. In the work at hand, we have combined these two approaches to create a pretargeted PET imaging strategy based on the rapid and bioorthogonal inverse electron demand Diels-Alder reaction between a (64)Cu-labeled tetrazine radioligand ((64)Cu-Tz SarAr) and a site-specifically modified huA33-trans-cyclooctene immunoconjugate ((ss)huA33-PEG12-TCO). A bioconjugation strategy that harnesses enzymatic transformations and strain-promoted azide-alkyne click chemistry was used to site specifically append PEGylated TCO moieties to the heavy chain glycans of the colorectal cancer-targeting huA33 antibody. Preclinical in vivo validation studies were performed in athymic nude mice bearing A33 antigen-expressing SW1222 human colorectal carcinoma xenografts. To this end, mice were administered (ss)huA33-PEG12-TCO via tail vein injection and-following accumulation intervals of 24 or 48 h-(64)Cu-Tz-SarAr. PET imaging and biodistribution studies reveal that this strategy clearly delineates tumor tissue as early as 1 h post-injection (6.7 +/- 1.7%ID/g at 1 h p.i.), producing images with excellent contrast and high tumor-to-background activity concentration ratios (tumor:muscle = 21.5 +/- 5.6 at 24 h p.i.). Furthermore, dosimetric calculations illustrate that this pretargeting approach produces only a fraction of the overall effective dose (0.0214 mSv/MBq; 0.079 rem/mCi) of directly labeled radioimmunoconjugates. Ultimately, this method effectively facilitates the high contrast pretargeted PET imaging of colorectal carcinoma using a site-specifically modified immunoconjugate. PMID- 27356889 TI - Pyoderma gangrenosum during pregnancy - treatment options revisited. AB - BACKGROUND: Pyoderma gangrenosum (PG) is a rare, ulcerating neutrophilic dermatosis of unknown aetiology; PG during pregnancy is particularly rare. The disease is frequently associated with immune-mediated, inflammatory diseases. OBJECTIVE: Diagnosis of PG can be challenging and relies upon exclusion of other causes such as traumas, infections, vascular diseases or neoplasms. Treatment options during pregnancy are limited. METHODS: To evaluate current treatment options for PG during pregnancy, we present a case of multilocular PG during the patient's first trimester. In conjunction with a comprehensive review of previously published cases of PG during gravidity, we discuss available treatment modalities including immunosuppressants and TNFalpha inhibitors. RESULTS: Our patient highlights the importance of including PG as a potential differential diagnosis of cutaneous ulcers during gravidity. Treatment with systemic glucocorticoids is effective and safe for the health of the mother and the unborn. CONCLUSION: In pregnant females, it is particularly important to diagnose PG and control disease activity due to the risk of pathergy and wound healing deficiencies during delivery and post-partum. A limited number of treatment options are available to date, which require a precise risk-benefit evaluation. PMID- 27356888 TI - Screening of gene signatures for rheumatoid arthritis and osteoarthritis based on bioinformatics analysis. AB - The current study aimed to identify gene signatures during rheumatoid arthritis (RA) and osteoarthritis (OA), and used these to elucidate the underlying modular mechanisms. Using the Gene Expression Omnibus database, the present study obtained the GSE7669 mRNA expression microarray data from RA and OA synovial fibroblasts (n=6 each). The differentially expressed genes (DEGs) in RA synovial samples compared with OA samples were identified using the Linear Models for Microarray Analysis package. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Database for Annotation Visualization and Integrated Discovery. A protein-protein interaction network was constructed and the modules were further analyzed using the Molecular Complex Detection plugin of Cytoscape. A total of 181 DEGs were identified by comparing RA and OA synovial samples (96 up- and 85 downregulated genes). The significant DEGs in module 1, including collagen, type I, alpha 1 (COL1A1), COL3A1, COL4A1 and COL11A1, were predominantly enriched in the extracellular matrix (ECM)-receptor interaction and focal adhesion pathways. Additionally, significant DEGs in module 2, including radical S-adenosyl methionine domain containing 2 (RSAD2), 2'-5'-oligoadenylate synthetase 2 (OAS2), myxovirus (influenza virus) resistance 1 (MX1) and ISG15 ubiquitin-like modifier (ISG15), were predominantly associated with immune function pathways. In conclusion, the present study indicated that RSAD2, OAS2, MX1 and ISG15 may be notable gene signatures in RA development via regulation of the immune response. COL3A1, COL4A1, COL1A1 and COL11A1 may be important gene signatures in OA development via involvement in the pathways of ECM-receptor interactions and focal adhesions. PMID- 27356890 TI - Global stability of a class of futile cycles. AB - In this paper, we prove the global asymptotic stability of a class of mass action futile cycle networks which includes a model of processive multisite phosphorylation networks. The proof consists of two parts. In the first part, we prove that there is a unique equilibrium in every positive compatibility class. In the second part, we make use of a piecewise linear in rates Lyapunov function in order to prove the global asymptotic stability of the unique equilibrium corresponding to a given initial concentration vector. The main novelty of the paper is the use of a simple algebraic approach based on the intermediate value property of continuous functions in order to prove the uniqueness of equilibrium in every positive compatibility class. PMID- 27356891 TI - Undefined familial colorectal cancer and the role of pleiotropism in cancer susceptibility genes. AB - Although family history is a major risk factor for colorectal cancer (CRC) a genetic diagnosis cannot be obtained in over 50 % of familial cases when screened for known CRC cancer susceptibility genes. The genetics of undefined-familial CRC is complex and recent studies have implied additional clinically actionable mutations for CRC in susceptibility genes for other cancers. To clarify the contribution of non-CRC susceptibility genes to undefined-familial CRC we conducted a mutational screen of 114 cancer susceptibility genes in 847 patients with early-onset undefined-familial CRC and 1609 controls by analysing high coverage exome sequencing data. We implemented American College of Medical Genetics and Genomics standards and guidelines for assigning pathogenicity to variants. Globally across all 114 cancer susceptibility genes no statistically significant enrichment of likely pathogenic variants was shown (6.7 % cases 57/847, 5.3 % controls 85/1609; P = 0.15). Moreover there was no significant enrichment of mutations in genes such as TP53 or BRCA2 which have been proposed for clinical testing in CRC. In conclusion, while we identified genes that may be considered interesting candidates as determinants of CRC risk warranting further research, there is currently scant evidence to support a role for genes other than those responsible for established CRC syndromes in the clinical management of familial CRC. PMID- 27356892 TI - Enhanced In Vivo Tumor Detection by Active Tumor Cell Targeting Using Multiple Tumor Receptor-Binding Peptides Presented on Genetically Engineered Human Ferritin Nanoparticles. AB - Human ferritin heavy-chain nanoparticle (hFTH) is genetically engineered to present tumor receptor-binding peptides (affibody and/or RGD-derived cyclic peptides, named 4CRGD here) on its surface. The affibody and 4CRGD specifically and strongly binds to human epidermal growth factor receptor I (EGFR) and human integrin alphavbeta3, respectively, which are overexpressed on various tumor cells. Through in vitro culture of EGFR-overexpressing adenocarcinoma (MDA-MB 468) and integrin-overexpressing glioblastoma cells (U87MG), it is clarified that specific interactions between receptors on tumor cells and receptor-binding peptides on engineered hFTH is critical in active tumor cell targeting. After labeling with the near-infrared fluorescence dye (Cy5.5) and intravenouse injection into MDA-MB-468 or U87MG tumor-bearing mice, the recombinant hFTHs presenting either peptide or both of affibody and 4CRGD are successfully delivered to and retained in the tumor for a prolonged period of time. In particular, the recombinant hFTH presenting both affibody and 4CRGD notably enhances in vivo detection of U87MG tumors that express heterogeneous receptors, integrin and EGFR, compared to the other recombinant hFTHs presenting either affibody or 4CRGD only. Like affibody and 4CRGD used in this study, other multiple tumor receptor-binding peptides can be also genetically introduced to the hFTH surface for actively targeting of in vivo tumors with heterogenous receptors. PMID- 27356893 TI - Proteomic Analysis of Exosomes and Exosome-Free Conditioned Media From Human Osteosarcoma Cell Lines Reveals Secretion of Proteins Related to Tumor Progression. AB - Osteosarcomas are the most prevalent bone tumors in pediatric patients, but can also occur later in life. Bone tumors have the potential to metastasize to lung and occasionally other vital organs. To understand how osteosarcoma cells interact with their micro-environment to support bone tumor progression and metastasis, we analyzed secreted proteins and exosomes from three human osteosarcoma cell lines. Exosome isolation was validated by transmission electron microscopy (TEM) and immuno-blotting for characteristic biomarkers (CD63, CD9, and CD81). Exosomal and soluble proteins (less than 100 kDa) were identified by mass spectrometry analysis using nanoLC-MS/MS and classified by functional gene ontology clustering. We identified a secretome set of >3,000 proteins for both fractions, and detected proteins that are either common or unique among the three osteosarcoma cell lines. Protein ontology comparison of proteomes from exosomes and exosome-free fractions revealed differences in the enrichment of functional categories associated with different biological processes, including those related to tumor progression (i.e., angiogenesis, cell adhesion, and cell migration). The secretome characteristics of osteosarcoma cells are consistent with the pathological properties of tumor cells with metastatic potential. J. Cell. Biochem. 118: 351-360, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27356894 TI - Kynurenine Reduces Memory CD4 T-Cell Survival by Interfering with Interleukin-2 Signaling Early during HIV-1 Infection. AB - Early HIV-1 infection is characterized by enhanced tryptophan catabolism, which contributes to immune suppression and disease progression. However, the mechanism by which kynurenine, a tryptophan-related metabolite, induces immune suppression remains poorly understood. Herein, we show that the increased production of kynurenine correlates with defective interleukin-2 (IL-2) signaling in memory CD4 T cells from HIV-infected subjects. Defective IL-2 signaling in these subjects, which drives reduced protection from Fas-mediated apoptosis, was also associated with memory CD4 T-cell loss. Treatment of memory CD4 T cells with the concentration of kynurenine found in plasma inhibited IL-2 signaling through the production of reactive oxygen species. We further show that IL-2 signaling in memory CD4 T cells is improved by the antioxidant N-acetylcysteine. Early initiation of antiretroviral therapy restored the IL-2 response in memory CD4 T cells by reducing reactive oxygen species and kynurenine production. The study findings provide a kynurenine-dependent mechanism through IL-2 signaling for reduced CD4 T-cell survival, which can be reversed by early treatment initiation in HIV-1 infection. IMPORTANCE: The persistence of functional memory CD4 T cells represents the basis for long-lasting immune protection in individuals after exposure to HIV-1. Unfortunately, primary HIV-1 infection results in the massive loss of these cells within weeks of infection, which is mainly driven by inflammation and massive infection by the virus. These new findings show that the enhanced production of kynurenine, a metabolite related to tryptophan catabolism, also impairs memory CD4 T-cell survival and interferes with IL-2 signaling early during HIV-1 infection. PMID- 27356895 TI - In Vivo Examination of Mouse APOBEC3- and Human APOBEC3A- and APOBEC3G-Mediated Restriction of Parvovirus and Herpesvirus Infection in Mouse Models. AB - APOBEC3 knockout and human APOBEC3A and -3G transgenic mice were tested for their ability to be infected by the herpesviruses herpes simplex virus 1 and murine herpesvirus 68 and the parvovirus minute virus of mice (MVM). Knockout, APOBEC3A and APOBEC3G transgenic, and wild-type mice were equally infected by the herpesviruses, while APOBEC3A but not mouse APOBEC3 conferred resistance to MVM. No viruses showed evidence of cytidine deamination by mouse or human APOBEC3s. These data suggest that in vitro studies implicating APOBEC3 proteins in virus resistance may not reflect their role in vivo IMPORTANCE: It is well established that APOBEC3 proteins in different species are a critical component of the host antiretroviral defense. Whether these proteins also function to inhibit other viruses is not clear. There have been a number of in vitro studies suggesting that different APOBEC3 proteins restrict herpesviruses and parvoviruses, among others, but whether they also work in vivo has not been demonstrated. Our studies looking at the role of mouse and human APOBEC3 proteins in transgenic and knockout mouse models of viral infection suggest that these restriction factors are not broadly antiviral and demonstrate the importance of testing their activity in vivo. PMID- 27356896 TI - Development of Potent Antiviral Drugs Inspired by Viral Hexameric DNA-Packaging Motors with Revolving Mechanism. AB - The intracellular parasitic nature of viruses and the emergence of antiviral drug resistance necessitate the development of new potent antiviral drugs. Recently, a method for developing potent inhibitory drugs by targeting biological machines with high stoichiometry and a sequential-action mechanism was described. Inspired by this finding, we reviewed the development of antiviral drugs targeting viral DNA-packaging motors. Inhibiting multisubunit targets with sequential actions resembles breaking one bulb in a series of Christmas lights, which turns off the entire string. Indeed, studies on viral DNA packaging might lead to the development of new antiviral drugs. Recent elucidation of the mechanism of the viral double-stranded DNA (dsDNA)-packaging motor with sequential one-way revolving motion will promote the development of potent antiviral drugs with high specificity and efficiency. Traditionally, biomotors have been classified into two categories: linear and rotation motors. Recently discovered was a third type of biomotor, including the viral DNA-packaging motor, beside the bacterial DNA translocases, that uses a revolving mechanism without rotation. By analogy, rotation resembles the Earth's rotation on its own axis, while revolving resembles the Earth's revolving around the Sun (see animations at http://rnanano.osu.edu/movie.html). Herein, we review the structures of viral dsDNA-packaging motors, the stoichiometries of motor components, and the motion mechanisms of the motors. All viral dsDNA-packaging motors, including those of dsDNA/dsRNA bacteriophages, adenoviruses, poxviruses, herpesviruses, mimiviruses, megaviruses, pandoraviruses, and pithoviruses, contain a high-stoichiometry machine composed of multiple components that work cooperatively and sequentially. Thus, it is an ideal target for potent drug development based on the power function of the stoichiometries of target complexes that work sequentially. PMID- 27356898 TI - Viral FGARAT Homolog ORF75 of Rhesus Monkey Rhadinovirus Effects Proteasomal Degradation of the ND10 Components SP100 and PML. AB - Nuclear domain 10 (ND10) components restrict herpesviral infection, and herpesviruses antagonize this restriction by a variety of strategies, including degradation or relocalization of ND10 proteins. The rhesus monkey rhadinovirus (RRV) shares many key biological features with the closely related Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus 8) and readily infects cells of both human and rhesus monkey origin. We used the clustered regularly interspaced short palindromic repeat-Cas9 (CRISPR-Cas9) technique to generate knockout (ko) cells for each of the four ND10 components, PML, SP100, DAXX, and ATRX. These ko cells were analyzed with regard to permissiveness for RRV infection. In addition, we analyzed the fate of the individual ND10 components in infected cells by immunofluorescence and Western blotting. Knockout of the ND10 component DAXX markedly increased RRV infection, while knockout of PML or SP100 had a less pronounced effect. In line with these observations, RRV infection resulted in rapid degradation of SP100, followed by degradation of PML and the loss of ND10 structures, whereas the protein levels of ATRX and DAXX remained constant. Notably, inhibition of the proteasome but not inhibition of de novo gene expression prevented the loss of SP100 and PML in cells that did not support lytic replication, compatible with proteasomal degradation of these ND10 components through the action of a viral tegument protein. Expression of the RRV FGARAT homolog ORF75 was sufficient to effect the loss of SP100 and PML in transfected or transduced cells, implicating ORF75 as the viral effector protein. IMPORTANCE: Our findings highlight the antiviral role of ND10 and its individual components and further establish the viral FGARAT homologs of the gammaherpesviruses to be important viral effectors that counteract ND10 instituted intrinsic immunity. Surprisingly, even closely related viruses like KSHV and RRV evolved to use different strategies to evade ND10-mediated restriction. RRV first targets SP100 for degradation and then targets PML with a delayed kinetic, a strategy which clearly differs from that of other gammaherpesviruses. Despite efficient degradation of these two major ND10 components, RRV is still restricted by DAXX, another abundant ND10 component, as evidenced by a marked increase in RRV infection and replication upon knockout of DAXX. Taken together, our findings substantiate PML, SP100, and DAXX as key antiviral proteins, in that the first two are targeted for degradation by RRV and the last one still potently restricts replication of RRV. PMID- 27356897 TI - Flow Cytometric and Cytokine ELISpot Approaches To Characterize the Cell-Mediated Immune Response in Ferrets following Influenza Virus Infection. AB - Influenza virus infections represent a significant socioeconomic and public health burden worldwide. Although ferrets are considered by many to be ideal for modeling human responses to influenza infection and vaccination, efforts to understand the cellular immune response have been severely hampered by a paucity of standardized procedures and reagents. In this study, we developed flow cytometric and T cell enzyme-linked immunosorbent spot (ELISpot) approaches to characterize the leukocyte composition and antigen-specific T cell response within key lymphoid tissues following influenza virus infection in ferrets. Through a newly designed and implemented set of serological reagents, we used multiparameter flow cytometry to directly quantify the frequency of CD4(+) and CD8(+) T cells, Ig(+) B cells, CD11b(+) myeloid-derived cells, and major histocompatibility complex (MHC) class II-positive antigen-presenting cells (APCs) both prior to and after intranasal infection with A/California/04/09 (H1N1). We found that the leukocyte composition was altered at 10 days postinfection, with notable gains in the frequency of T cells and myeloid cells within the draining lymph node. Furthermore, these studies revealed that the antigen specificity of influenza virus-reactive CD4 and CD8 T cells was very broad, with recognition of the viral HA, NA, M1, NS1, and NP proteins, and that total reactivity to influenza virus postinfection represented approximately 0.1% of the circulating peripheral blood mononuclear cells (PBMC). Finally, we observed distinct patterns of reactivity between individual animals, suggesting heterogeneity at the MHC locus in ferrets within commercial populations, a finding of considerable interest in efforts to move the ferret model forward for influenza vaccine and challenge studies. IMPORTANCE: Ferrets are an ideal animal model to study transmission, diseases, and vaccine efficacies of respiratory viruses because of their close anatomical and physiological resemblances to humans. However, a lack of reagents has limited our understanding of the cell mediated immune response following infection and vaccination. In this study, we used cross-reactive and ferret-specific antibodies to study the leukocyte composition and antigen-specific CD4 and CD8 T cell responses following influenza A/California/04/09 (H1N1) virus infection. These studies revealed strikingly distinct patterns of reactivity between CD4 and CD8 T cells, which were overlaid with differences in protein-specific responses between individual animals. Our results provide a first, in-depth look at the T cell repertoire in response to influenza infection and suggest that there is considerable heterogeneity at the MHC locus, which is akin to that in humans and an area of intense research interest. PMID- 27356899 TI - Structure-Function Analysis of the phiX174 DNA-Piloting Protein Using Length Altering Mutations. AB - Although the phiX174 H protein is monomeric during procapsid morphogenesis, 10 proteins oligomerize to form a DNA translocating conduit (H-tube) for penetration. However, the timing and location of H-tube formation are unknown. The H-tube's highly repetitive primary and quaternary structures made it amenable to a genetic analysis using in-frame insertions and deletions. Length-altered proteins were characterized for the ability to perform the protein's three known functions: participation in particle assembly, genome translocation, and stimulation of viral protein synthesis. Insertion mutants were viable. Theoretically, these proteins would produce an assembled tube exceeding the capsid's internal diameter, suggesting that virions do not contain a fully assembled tube. Lengthened proteins were also used to test the biological significance of the crystal structure. Particles containing H proteins of two different lengths were significantly less infectious than both parents, indicating an inability to pilot DNA. Shortened H proteins were not fully functional. Although they could still stimulate viral protein synthesis, they either were not incorporated into virions or, if incorporated, failed to pilot the genome. Mutant proteins that failed to incorporate contained deletions within an 85-amino-acid segment, suggesting the existence of an incorporation domain. The revertants of shortened H protein mutants fell into two classes. The first class duplicated sequences neighboring the deletion, restoring wild-type length but not wild-type sequence. The second class suppressed an incorporation defect, allowing the use of the shortened protein. IMPORTANCE: The H-tube crystal structure represents the first high-resolution structure of a virally encoded DNA translocating conduit. It has similarities with other viral proteins through which DNA must travel, such as the alpha-helical barrel domains of P22 portal proteins and T7 proteins that form tail tube extensions during infection. Thus, the H protein serves as a paradigm for the assembly and function of long alpha helical supramolecular structures and nanotubes. Highly repetitive in primary and quaternary structure, they are amenable to structure-function analyses using in frame insertions and deletions as presented herein. PMID- 27356900 TI - The Influenza A Virus Genotype Determines the Antiviral Function of NF-kappaB. AB - The role of NF-kappaB in influenza A virus (IAV) infection does not reveal a coherent picture, as pro- and also antiviral functions of this transcription factor have been described. To address this issue, we used clustered regularly interspaced short palindromic repeat with Cas9 (CRISPR-Cas9)-mediated genome engineering to generate murine MLE-15 cells lacking two essential components of the NF-kappaB pathway. Cells devoid of either the central NF-kappaB essential modulator (NEMO) scaffold protein and thus defective in IkappaB kinase (IKK) activation or cells not expressing the NF-kappaB DNA-binding and transactivation subunit p65 were tested for propagation of the SC35 virus, which has an avian host range, and its mouse-adapted variant, SC35M. While NF-kappaB was not relevant for replication of SC35M, the absence of NF-kappaB activity increased replication of the nonadapted SC35 virus. This antiviral effect of NF-kappaB was most prominent upon infection of cells with low virus titers as they usually occur during the initiation phase of IAV infection. The defect in NF-kappaB signaling resulted in diminished IAV-triggered phosphorylation of interferon regulatory factor 3 (IRF3) and expression of the antiviral beta interferon (IFN beta) gene. To identify the viral proteins responsible for NF-kappaB dependency, reassortant viruses were generated by reverse genetics. SC35 viruses containing the SC35M segment encoding neuraminidase (NA) were completely inert to the inhibitory effect of NF-kappaB, emphasizing the importance of the viral genotype for susceptibility to the antiviral functions of NF-kappaB. IMPORTANCE: This study addresses two different issues. First, we investigated the role of the host cell transcription factor NF-kappaB in IAV replication by genetic manipulation of IAVs by reverse genetics combined with targeted genome engineering of host cells using CRISPR-Cas9. The analysis of these two highly defined genetic systems indicated that the IAV genotype can influence whether NF-kappaB displays an antiviral function and thus might in part explain incoherent results from the literature. Second, we found that perturbation of NF-kappaB function greatly improved the growth of a nonadapted IAV, suggesting that NF-kappaB may contribute to the maintenance of the host species barrier. PMID- 27356902 TI - The Evolutionary Histories of Antiretroviral Proteins SERINC3 and SERINC5 Do Not Support an Evolutionary Arms Race in Primates. AB - Molecular evolutionary arms races between viruses and their hosts are important drivers of adaptation. These Red Queen dynamics have been frequently observed in primate retroviruses and their antagonists, host restriction factor genes, such as APOBEC3F/G, TRIM5-alpha, SAMHD1, and BST-2. Host restriction factors have experienced some of the most intense and pervasive adaptive evolution documented in primates. Recently, two novel host factors, SERINC3 and SERINC5, were identified as the targets of HIV-1 Nef, a protein crucial for the optimal infectivity of virus particles. Here, we compared the evolutionary fingerprints of SERINC3 and SERINC5 to those of other primate restriction factors and to a set of other genes with diverse functions. SERINC genes evolved in a manner distinct from the canonical arms race dynamics seen in the other restriction factors. Despite their antiviral activity against HIV-1 and other retroviruses, SERINC3 and SERINC5 have a relatively uneventful evolutionary history in primates. IMPORTANCE: Restriction factors are host proteins that block viral infection and replication. Many viruses, like HIV-1 and related retroviruses, evolved accessory proteins to counteract these restriction factors. The importance of these interactions is evidenced by the intense adaptive selection pressures that dominate the evolutionary histories of both the host and viral genes involved in this so-called arms race. The dynamics of these arms races can point to mechanisms by which these viral infections can be prevented. Two human genes, SERINC3 and SERINC5, were recently identified as targets of an HIV-1 accessory protein important for viral infectivity. Unexpectedly, we found that these SERINC genes, unlike other host restriction factor genes, show no evidence of a recent evolutionary arms race with viral pathogens. PMID- 27356901 TI - Establishment and Reversal of HIV-1 Latency in Naive and Central Memory CD4+ T Cells In Vitro. AB - The latent HIV-1 reservoir primarily resides in resting CD4(+) T cells which are a heterogeneous population composed of both naive (TN) and memory cells. In HIV-1 infected individuals, viral DNA has been detected in both naive and memory CD4(+) T cell subsets although the frequency of HIV-1 DNA is typically higher in memory cells, particularly in the central memory (TCM) cell subset. TN and TCM cells are distinct cell populations distinguished by many phenotypic and physiological differences. In this study, we used a primary cell model of HIV-1 latency that utilizes direct infection of highly purified TN and TCM cells to address differences in the establishment and reversal of HIV-1 latency. Consistent with what is seen in vivo, we found that HIV-1 infected TN cells less efficiently than TCM cells. However, when the infected TN cells were treated with latency reversing agents, including anti-CD3/CD28 antibodies, phorbol myristate acetate/phytohemagglutinin, and prostratin, as much (if not more) extracellular virion-associated HIV-1 RNA was produced per infected TN cell as per infected TCM cell. There were no major differences in the genomic distribution of HIV-1 integration sites between TN and TCM cells that accounted for these observed differences. We observed decay of the latent HIV-1 cells in both T cell subsets after exposure to each of the latency-reversing agents. Collectively, these data highlight significant differences in the establishment and reversal of HIV-1 latency in TN and TCM CD4(+) T cells and suggest that each subset should be independently studied in preclinical and clinical studies. IMPORTANCE: The latent HIV-1 reservoir is frequently described as residing within resting memory CD4(+) T cells. This is largely due to the consistent finding that memory CD4(+) T cells, specifically the central (TCM) and transitional memory compartments, harbor the highest levels of HIV-1 DNA in individuals on suppressive therapy. This has yielded little research into the contribution of CD4(+) naive T (TN) cells to the latent reservoir. In this study, we show that although TN cells harbor significantly lower levels of HIV-1 DNA, following latency reversal, they produced as many virions as did the TCM cells (if not more virions). This suggests that latently infected TN cells may be a major source of virus following treatment interruption or failure. These findings highlight the need for a better understanding of the establishment and reversal of HIV-1 latency in TN cells in evaluating therapeutic approaches to eliminate the latent reservoir. PMID- 27356903 TI - Distinct Particle Morphologies Revealed through Comparative Parallel Analyses of Retrovirus-Like Particles. AB - The Gag protein is the main retroviral structural protein, and its expression alone is usually sufficient for production of virus-like particles (VLPs). In this study, we sought to investigate-in parallel comparative analyses-Gag cellular distribution, VLP size, and basic morphological features using Gag expression constructs (Gag or Gag-YFP, where YFP is yellow fluorescent protein) created from all representative retroviral genera: Alpharetrovirus, Betaretrovirus, Deltaretrovirus, Epsilonretrovirus, Gammaretrovirus, Lentivirus, and Spumavirus. We analyzed Gag cellular distribution by confocal microscopy, VLP budding by thin-section transmission electron microscopy (TEM), and general morphological features of the VLPs by cryogenic transmission electron microscopy (cryo-TEM). Punctate Gag was observed near the plasma membrane for all Gag constructs tested except for the representative Beta- and Epsilonretrovirus Gag proteins. This is the first report of Epsilonretrovirus Gag localizing to the nucleus of HeLa cells. While VLPs were not produced by the representative Beta- and Epsilonretrovirus Gag proteins, the other Gag proteins produced VLPs as confirmed by TEM, and morphological differences were observed by cryo-TEM. In particular, we observed Deltaretrovirus-like particles with flat regions of electron density that did not follow viral membrane curvature, Lentivirus-like particles with a narrow range and consistent electron density, suggesting a tightly packed Gag lattice, and Spumavirus-like particles with large envelope protein spikes and no visible electron density associated with a Gag lattice. Taken together, these parallel comparative analyses demonstrate for the first time the distinct morphological features that exist among retrovirus-like particles. Investigation of these differences will provide greater insights into the retroviral assembly pathway. IMPORTANCE: Comparative analysis among retroviruses has been critically important in enhancing our understanding of retroviral replication and pathogenesis, including that of important human pathogens such as human T-cell leukemia virus type 1 (HTLV-1) and HIV-1. In this study, parallel comparative analyses have been used to study Gag expression and virus-like particle morphology among representative retroviruses in the known retroviral genera. Distinct differences were observed, which enhances current knowledge of the retroviral assembly pathway. PMID- 27356904 TI - Immunization with Attenuated Equine Herpesvirus 1 Strain KyA Induces Innate Immune Responses That Protect Mice from Lethal Challenge. AB - Equine herpesvirus 1 (EHV-1) is a major pathogen affecting equines worldwide. The virus causes respiratory disease, abortion, and, in some cases, neurological disease. EHV-1 strain KyA is attenuated in the mouse and equine, whereas wild type strain RacL11 induces severe inflammation of the lung, causing infected mice to succumb at 4 to 6 days postinfection. Our previous results showed that KyA immunization protected CBA mice from pathogenic RacL11 challenge at 2 and 4 weeks postimmunization and that KyA infection elicited protective humoral and cell mediated immune responses. To investigate the protective mechanisms of innate immune responses to KyA, KyA-immunized mice were challenged with RacL11 at various times postvaccination. KyA immunization protected mice from RacL11 challenge at 1 to 7 days postimmunization. Immunized mice lost less than 10% of their body weight and rapidly regained weight. Virus titers in the lungs of KyA immunized mice were 1,000-fold lower at 2 days post-RacL11 challenge than virus titers in the lungs of nonimmunized mice, indicating accelerated virus clearance. Affymetrix microarray analysis revealed that gamma interferon (IFN-gamma) and 16 antiviral interferon-stimulated genes (ISGs) were upregulated 3.1- to 48.2-fold at 8 h postchallenge in the lungs of RacL11-challenged mice that had been immunized with KyA. Murine IFN-gamma inhibited EHV-1 infection of murine alveolar macrophages and protected mice against lethal EHV-1 challenge, suggesting that IFN-gamma expression is important in mediating the protection elicited by KyA immunization. These results suggest that EHV-1 KyA may be used as a live attenuated EHV-1 vaccine as well as a prophylactic agent in horses. IMPORTANCE: Viral infection of cells initiates a signal cascade of events that ultimately attempts to limit viral replication and prevent infection through the expression of host antiviral proteins. In this study, we show that EHV-1 KyA immunization effectively protected CBA mice from pathogenic RacL11 challenge at 1 to 7 days postvaccination and increased the expression of IFN-gamma and 16 antiviral interferon-stimulated genes (ISGs). The administration of IFN-gamma blocked EHV-1 replication in murine alveolar macrophages and mouse lungs and protected mice from lethal challenge. To our knowledge, this is the first report of an attenuated EHV-1 vaccine that protects the animal at 1 to 7 days postimmunization by innate immune responses. Our findings suggested that IFN-gamma serves as a novel prophylactic agent and may offer new strategies for the development of anti EHV-1 agents in the equine. PMID- 27356906 TI - Comparison of outcomes after umbilical cord blood and unmanipulated haploidentical hematopoietic stem cell transplantation in children with high-risk acute lymphoblastic leukemia. AB - Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective therapy for children with high-risk acute lymphoblastic leukemia (ALL). Human leukocyte antigen (HLA)-haploidentical HSCT (haplo-HSCT) or umbilical cord blood transplantation (UCBT) are both important alternative sources of stem cells for those without an HLA-identical sibling donor or unrelated matched donor. We aimed to compare the therapeutic effects of single UCBT and unmanipulated haplo-HSCT in high-risk ALL children (n = 129). Hematopoietic recovery was significantly faster in haplo-HSCT recipients than in UCBT recipients. The 2-year cumulative incidences of relapse in the haplo-HSCT and UCBT groups were 16.1% and 24.1%, respectively (p = 0.169). The 2-year cumulative incidences of non-relapse mortality in the haplo-HSCT and UCBT groups were 12.8% and 18.8%, respectively (p = 0.277). The 2-year probabilities of overall survival in the haplo-HSCT and UCBT groups were 82.0% and 69.6%, respectively (p = 0.071), and the 2-year probability of disease-free survival in the haplo-HSCT group was higher than in the UCBT group (71.0% vs. 57.2%, p = 0.040). However, several variables (such as leukocyte count and cytogenetics at diagnosis) were different between the groups, and a possible center effect should also be considered. In addition, only mild and moderate chronic graft-versus-host disease (GVHD) was associated with significantly improved survival compared to those without chronic GVHD in multivariate analysis. Thus, our results show that both unmanipulated haplo-HSCT and UCBT are valid for high-risk ALL children lacking a HLA matched donor, and both strategies expand the donor pool for children in need. PMID- 27356905 TI - Major Histocompatibility Complex Class II HLA-DRalpha Is Downregulated by Kaposi's Sarcoma-Associated Herpesvirus-Encoded Lytic Transactivator RTA and MARCH8. AB - Kaposi's sarcoma-associated herpesvirus (KSHV) maintains two modes of life cycle, the latent and lytic phases. To evade the attack of the cell host's immune system, KSHV switches from the lytic to the latent phase, a phase in which only a few of viral proteins are expressed. The mechanism by which KSHV evades the attack of the immune system and establishes latency has not been fully understood. Major histocompatibility complex class II (MHC-II) molecules are key components of the immune system defense mechanism against viral infections. Here we report that HLA-DRalpha, a member of the MHC-II molecules, was downregulated by the replication and transcription activator (RTA) protein encoded by KSHV ORF50, an important regulator of the viral life cycle. RTA not only downregulated HLA-DRalpha at the protein level through direct binding and degradation through the proteasome pathway but also indirectly downregulated the protein level of HLA DRalpha by enhancing the expression of MARCH8, a member of the membrane associated RING-CH (MARCH) proteins. Our findings indicate that KSHV RTA facilitates evasion of the virus from the immune system through manipulation of HLA-DRalpha. IMPORTANCE: Kaposi's sarcoma-associated herpesvirus (KSHV) has a causal role in a number of human cancers, and its persistence in infected cells is controlled by the host's immune system. The mechanism by which KSHV evades an attack by the immune system has not been well understood. This work represents studies which identify a novel mechanism by which the virus can facilitate evasion of an immune system. We now show that RTA, the replication and transcription activator encoded by KSHV (ORF50), can function as an E3 ligase to degrade HLA-DRalpha. It can directly bind and induce degradation of HLA-DRalpha through the ubiquitin-proteasome degradation pathway. In addition to the direct regulation of HLA-DRalpha, RTA can also indirectly downregulate the level of HLA DRalpha protein by upregulating transcription of MARCH8. Increased MARCH8 results in the downregulation of HLA-DRalpha. Furthermore, we also demonstrate that expression of HLA-DRalpha was impaired in KSHV de novo infection. PMID- 27356907 TI - Understanding the complement-mediated glomerular diseases: focus on membranoproliferative glomerulonephritis and C3 glomerulopathies. AB - An enhanced understanding of the role of complement in the pathogenesis of membranoproliferative glomerulonephritis has led to reclassification of the latter into immunoglobulin-mediated and non-immunoglobulin-mediated disease. The new classification schema resulted in improved diagnostic clinical algorithms, while it brought into light again the diseases, which are characterized by the presence of glomerular deposits, composed predominantly by C3, in the absence of significant amounts of immunoglobulins in renal biopsy, namely, C3 glomerulopathies (dense deposit disease and C3 glomerulonephritis). Despite the lack of randomized controlled trials following the advances in the understanding of the pathogenetic pathways involved in membranoproliferative glomerulonephritis, it is important that the new mechanistic approach has opened new roads for the exploration and discovery of targeted therapies. PMID- 27356908 TI - Sugar-Based Arylsulfonamide Carboxylates as Selective and Water-Soluble Matrix Metalloproteinase-12 Inhibitors. AB - Matrix metalloproteinase-12 (MMP-12) can be considered an attractive target to study selective inhibitors useful in the development of new therapies for lung and cardiovascular diseases. In this study, a new series of arylsulfonamide carboxylates, with increased hydrophilicity resulting from conjugation with a beta-N-acetyl-d-glucosamine moiety, were designed and synthesized as MMP-12 selective inhibitors. Their inhibitory activity was evaluated on human MMPs by using the fluorimetric assay, and a crystallographic analysis was performed to characterize their binding mode. Among these glycoconjugates, a nanomolar MMP-12 inhibitor with improved water solubility, compound 3 [(R)-2-(N-(2-(3-(2-acetamido 2-deoxy-beta-d-glucopyranosyl)thioureido)ethyl)biphenyl-4-ylsulfonamido)-3 methylbutanoic acid], was identified. PMID- 27356909 TI - Reduction of sodium content in spicy soups using monosodium glutamate. AB - BACKGROUND: Excessive dietary sodium intake causes several diseases, such as hypertension, cardiovascular and renal disease, etc. Hence, reducing sodium intake has been highly recommended. In this study the effect of monosodium glutamate (MSG), as an umami substance, on saltiness and sodium reduction was investigated. METHODS AND RESULTS: The trained panellists were presented with basic spicy soups (curry chicken and chili chicken) containing different amounts of sodium chloride (NaCl) (0-1.2%) and MSG (0-1.2%). They tasted the optimum concentrations of NaCl and MSG for the two spicy soups and the overall acceptability were 0.8% and 0.7%, respectively. There was no significant effect of spiciness level on the saltiness and umami taste of both soups. The optimum levels of combined NaCl and MSG for overall acceptance in the chili and curry soups were 0.3% and 0.7%, respectively. The results showed that with the addition of MSG, it is possible to reduce sodium intake without changing the overall acceptability of the spicy soup. A 32.5% reduction in sodium level is made feasible by adding 0.7% MSG to the spicy soups. CONCLUSIONS: This study suggests that low-sodium soups can be developed by the addition of appropriate amounts of MSG, while maintaining the acceptability of the spicy soups. It was also proven that it is feasible to reduce sodium intake by replacing NaCl with MSG. PMID- 27356910 TI - Dietary apigenin potentiates the inhibitory effect of interferon-alpha on cancer cell viability through inhibition of 26S proteasome-mediated interferon receptor degradation. AB - BACKGROUND: Type I interferons (IFN-alpha/beta) have broad and potent immunoregulatory and antiproliferative activities. However, it is still known whether the dietary flavonoids exhibit their antiviral and anticancer properties by modulating the function of type I IFNs. OBJECTIVE: This study aimed at determining the role of apigenin, a dietary plant flavonoid abundant in common fruits and vegetables, on the type I IFN-mediated inhibition of cancer cell viability. DESIGN: Inhibitory effect of apigenin on human 26S proteasome, a known negative regulator of type I IFN signaling, was evaluated in vitro. Molecular docking was conducted to know the interaction between apigenin and subunits of 26S proteasome. Effects of apigenin on JAK/STAT pathway, 26S proteasome-mediated interferon receptor stability, and cancer cells viability were also investigated. RESULTS: Apigenin was identified to be a potent inhibitor of human 26S proteasome in a cell-based assay. Apigenin inhibited the chymotrypsin-like, caspase-like, and trypsin-like activities of the human 26S proteasome and increased the ubiquitination of endogenous proteins in cells. Results from computational modeling of the potential interactions of apigenin with the chymotrypsin site (beta5 subunit), caspase site (beta1 subunit), and trypsin site (beta2 subunit) of the proteasome were consistent with the observed proteasome inhibitory activity. Apigenin enhanced the phosphorylation of signal transducer and activator of transcription proteins (STAT1 and STAT2) and promoted the endogenous IFN-alpha-regulated gene expression. Apigenin inhibited the IFN-alpha-stimulated ubiquitination and degradation of type I interferon receptor 1 (IFNAR1). Apigenin also sensitized the inhibitory effect of IFN-alpha on viability of cervical carcinoma HeLa cells. CONCLUSION: These results suggest that apigenin potentiates the inhibitory effect of IFN-alpha on cancer cell viability by activating JAK/STAT signaling pathway through inhibition of 26S proteasome-mediated IFNAR1 degradation. This may provide a novel mechanism for increasing the efficacy of IFN-alpha/beta. PMID- 27356911 TI - Plant hormones in interactions with the environment. PMID- 27356913 TI - Plasma Coenzyme Q10 Levels in Patients With Multiple System Atrophy. AB - IMPORTANCE: Multiple system atrophy (MSA) is an intractable neurodegenerative disease characterized by autonomic failure in addition to various combinations of parkinsonism, cerebellar ataxia, and pyramidal dysfunction. It has recently been reported that functionally impaired variants of COQ2, which encodes an essential enzyme in the biosynthetic pathway of coenzyme Q10 (CoQ10), are associated with MSA. However, little is known about the role of CoQ10 in the pathogenesis of MSA. OBJECTIVE: To compare the levels of plasma CoQ10 in patients with MSA with those in age-, sex-, and COQ2 genotype-matched controls. DESIGN, SETTING, AND PARTICIPANTS: We enrolled 44 Japanese patients with MSA and 39 Japanese controls from September 1, 2012, to December 31, 2015. Patients with MSA were diagnosed on the basis of the second consensus criteria by at least 2 neurologists. Plasma CoQ10 levels were measured by high-performance liquid chromatography with electrochemical detection. Sanger sequencing of COQ2 was performed to determine the COQ2 genotypes. Multiple logistic regression analysis was performed to determine the association between MSA and the plasma CoQ10 level. MAIN OUTCOMES AND MEASURES: Plasma CoQ10 levels in patients with MSA were compared with those in controls after adjusting for age, sex, and COQ2 genotype. RESULTS: Among 44 patients with MSA (mean [SD] age, 63.7 [8.3] years) and 39 controls (mean [SD] age, 60.3 [13.0] years), the mean (SD) plasma level of CoQ10 in patients with MSA was lower than that in controls (0.51 [0.22] vs 0.72 [0.42] ug/mL; P = .01) (difference between medians: -0.14; 95% CI, -0.25 to -0.03). The mean (SD) plasma levels of CoQ10 in patients with the cerebellar variant of MSA and those with the parkinsonian variant of MSA were 0.58 (0.19) and 0.49 (0.26) ug/mL, respectively. After adjusting for age, sex, and COQ2 genotype, the levels of plasma CoQ10 were significantly associated with MSA (95% CI, 0.10; range, 0.02 to 0.66) (P = .02). CONCLUSIONS AND RELEVANCE: Our data showed decreased levels of plasma CoQ10 in patients with MSA regardless of the COQ2 genotype, supporting a hypothesis that supplementation with CoQ10 is beneficial for patients with MSA. PMID- 27356912 TI - Genome-wide identification and analysis of rice genes preferentially expressed in pollen at an early developmental stage. AB - Microspore production using endogenous developmental programs has not been well studied. The main limitation is the difficulty in identifying genes preferentially expressed in pollen grains at early stages. To overcome this limitation, we collected transcriptome data from anthers and microspore/pollen and performed meta-expression analysis. Subsequently, we identified 410 genes showing preferential expression patterns in early developing pollen samples of both japonica and indica cultivars. The expression patterns of these genes are distinguishable from genes showing pollen mother cell or tapetum-preferred expression patterns. Gene Ontology enrichment and MapMan analyses indicated that microspores in rice are closely linked with protein degradation, nucleotide metabolism, and DNA biosynthesis and regulation, while the pollen mother cell or tapetum are strongly associated with cell wall metabolism, lipid metabolism, secondary metabolism, and RNA biosynthesis and regulation. We also generated transgenic lines under the control of the promoters of eight microspore-preferred genes and confirmed the preferred expression patterns in plants using the GUS reporting system. Furthermore, cis-regulatory element analysis revealed that pollen specific elements such as POLLEN1LELAT52, and 5659BOXLELAT5659 were commonly identified in the promoter regions of eight rice genes with more frequency than estimation. Our study will provide new sights on early pollen development in rice, a model crop plant. PMID- 27356916 TI - Role of the IL-1 Pathway in Dopaminergic Neurodegeneration and Decreased Voluntary Movement. AB - Interleukin-1 (IL-1), a proinflammatory cytokine synthesized and released by activated microglia, can cause dopaminergic neurodegeneration leading to Parkinson's disease (PD). However, it is uncertain whether IL-1 can act directly, or by exacerbating the harmful actions of other brain insults. To ascertain the role of the IL-1 pathway on dopaminergic neurodegeneration and motor skills during aging, we compared mice with impaired [caspase-1 knockout (casp1-/-)] or overactivated IL-1 activity [IL-1 receptor antagonist knockout (IL-1ra-/-)] to wild-type (wt) mice at young and middle age. Their motor skills were evaluated by the open-field and rotarod tests, and quantification of their dopamine neurons and activated microglia within the substantia nigra were performed by immunohistochemistry. IL-1ra-/- mice showed an age-related decline in motor skills, a reduced number of dopamine neurons, and an increase in activated microglia when compared to wt or casp1-/- mice. Casp1-/- mice had similar changes in motor skills and dopamine neurons, but fewer activated microglia cells than wt mice. Our results suggest that the overactivated IL-1 pathway occurring in IL-1ra /- mice in the absence of inflammatory interventions (e.g., intracerebral injections performed in animal models of PD) increased activated microglia, decreased the number of dopaminergic neurons, and reduced their motor skills. Decreased IL-1 activity in casp1-/- mice did not yield clear protective effects when compared with wt mice. In summary, in the absence of overt brain insults, chronic activation of the IL-1 pathway may promote pathological aspects of PD per se, but its impairment does not appear to yield advantages over wt mice. PMID- 27356917 TI - Evaluation of Oxidative Stress Parameters and Energy Metabolism in Cerebral Cortex of Rats Subjected to Sarcosine Administration. AB - Sarcosine is an N-methyl derivative of the amino acid glycine, and its elevation in tissues and physiological fluids of patients with sarcosinemia could reflect a deficient pool size of activated 1-carbon units. Sarcosinemia is a rare inherited metabolic condition associated with mental retardation. In the present study, we investigated the acute effect of sarcosine and/or creatine plus pyruvate on some parameters of oxidative stress and energy metabolism in cerebral cortex homogenates of 21-day-old Wistar rats. Acute administration of sarcosine induced oxidative stress and diminished the activities of adenylate kinase, GAPDH, complex IV, and mitochondrial and cytosolic creatine kinase. On the other hand, succinate dehydrogenase activity was enhanced in cerebral cortex of rats. Moreover, total sulfhydryl content was significantly diminished, while DCFH oxidation, TBARS content, and activities of SOD and GPx were significantly enhanced by acute administration of sarcosine. Co-administration of creatine plus pyruvate was effective in the prevention of alterations provoked by sarcosine administration on the oxidative stress and the enzymes of phosphoryltransfer network. These results indicate that acute administration of sarcosine may stimulate oxidative stress and alter the energy metabolism in cerebral cortex of rats. In case these effects also occur in humans, they may contribute, along with other mechanisms, to the neurological dysfunction of sarcosinemia, and creatine and pyruvate supplementation could be beneficial to the patients. PMID- 27356919 TI - Investigation of two- and three-bond carbon-hydrogen coupling constants in cinnamic acid based compounds. AB - Two- and three-bond coupling constants (2 JHC and 3 JHC ) were determined for a series of 12 substituted cinnamic acids using a selective 2D inphase/antiphase (IPAP)-single quantum multiple bond correlation (HSQMBC) and 1D proton coupled 13 C NMR experiments. The coupling constants from two methods were compared and found to give very similar values. The results showed coupling constant values ranging from 1.7 to 9.7 Hz and 1.0 to 9.6 Hz for the IPAP-HSQMBC and the direct 13 C NMR experiments, respectively. The experimental values of the coupling constants were compared with discrete density functional theory (DFT) calculated values and were found to be in good agreement for the 3 JHC . However, the DFT method under estimated the 2 JHC coupling constants. Knowing the limitations of the measurement and calculation of these multibond coupling constants will add confidence to the assignment of conformation or stereochemical aspects of complex molecules like natural products. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27356918 TI - Idiopathic Autism: Cellular and Molecular Phenotypes in Pluripotent Stem Cell Derived Neurons. AB - Autism spectrum disorder is a complex neurodevelopmental disorder whose pathophysiology remains elusive as a consequence of the unavailability for study of patient brain neurons; this deficit may potentially be circumvented by neural differentiation of induced pluripotent stem cells. Rare syndromes with single gene mutations and autistic symptoms have significantly advanced the molecular and cellular understanding of autism spectrum disorders; however, in aggregate, they only represent a fraction of all cases of autism. In an effort to define the cellular and molecular phenotypes in human neurons of non-syndromic autism, we generated induced pluripotent stem cells (iPSCs) from three male autism spectrum disorder patients who had no identifiable clinical syndromes, and their unaffected male siblings and subsequently differentiated these patient-specific stem cells into electrophysiologically active neurons. iPSC-derived neurons from these autistic patients displayed decreases in the frequency and kinetics of spontaneous excitatory postsynaptic currents relative to controls, as well as significant decreases in Na+ and inactivating K+ voltage-gated currents. Moreover, whole-genome microarray analysis of gene expression identified 161 unique genes that were significantly differentially expressed in autistic patient iPSC-derived neurons (>twofold, FDR < 0.05). These genes were significantly enriched for processes related to synaptic transmission, such as neuroactive ligand-receptor signaling and extracellular matrix interactions, and were enriched for genes previously associated with autism spectrum disorder. Our data demonstrate aberrant voltage-gated currents and underlying molecular changes related to synaptic function in iPSC-derived neurons from individuals with idiopathic autism as compared to unaffected siblings controls. PMID- 27356920 TI - Correlates of Clozapine Use after a First Episode of Schizophrenia: Results From a Long-term Prospective Study. AB - BACKGROUND: Earlier commencement of clozapine has been related to a better response in treatment-resistant schizophrenia. OBJECTIVES: To identify variables that predict clozapine use after a first episode of schizophrenia (FES). METHODS: Patients with FES and <=15 days of lifetime antipsychotic treatment were followed up during naturalistic treatment, and the patients who were initiated on clozapine were compared with those receiving non-clozapine antipsychotics for >=24 months regarding demographic and clinical baseline characteristics, adherence, and relapse patterns during follow-up. Treatment-resistant schizophrenia was defined as two or more antipsychotic trials of adequate dose for >=6 weeks. RESULTS: Twenty-eight patients who used clozapine and 77 non clozapine antipsychotic users were included. Clozapine was initiated after a mean of 2.5 +/- 1.1 adequate antipsychotic trials. Eight of the 28 clozapine-treated patients (28.6 %) began their clozapine treatment during the first 12 months of follow-up (mean 7.1 +/- 3.3 months) and their premorbid childhood adjustment was significantly worse than those who started clozapine later (mean 78.5 +/- 43.0 months). Compared with non-clozapine users, patients who started clozapine had significantly more relapses in the first 6 months of follow-up prior to clozapine use (35.7 vs. 11.7 %, p = 0.005), and were significantly more likely to have a first relapse despite treatment adherence (38.1 vs. 73.3 %, p = 0.01). In the multivariate analyses, antipsychotic polypharmacy and first relapse despite adherence to antipsychotic treatment independently predicted subsequent clozapine use. CONCLUSIONS: Clozapine use after a FES was predicted by a first relapse while being adherent to non-clozapine antipsychotics, especially if the first relapse occurred within the first 6 months. Developmental childhood difficulties predicted significantly earlier clozapine use. PMID- 27356921 TI - Asenapine: A Review in Schizophrenia. AB - Asenapine (Saphris((r)), Sycrest((r))) is an atypical antipsychotic that is administered sublingually twice daily and is approved for schizophrenia in the USA, Japan and other countries, but not in the EU. This article reviews the pharmacology, clinical efficacy and tolerability profile of asenapine in the treatment of adults with schizophrenia. Clinical trials with asenapine have demonstrated efficacy in terms of both positive and negative symptoms of schizophrenia, although findings have not always been consistent. Across three short-term (6-week) studies in acute schizophrenia (including one in Asian patients), asenapine was generally superior to placebo and had broadly similar efficacy to active controls in improving total scores on the Positive and Negative Syndrome Scale. A meta-analysis of four short-term trials with asenapine (that also included a negative study and a failed trial) also showed significant benefit with asenapine over placebo. In longer-term trials and extensions (up to ~3 years' duration), asenapine was effective relative to placebo in preventing relapse in schizophrenia, but was less effective than olanzapine in patients with schizophrenia or schizoaffective disorder (according to intent-to-treat LOCF analysis). However, in two trials in patients with persistent negative symptoms of schizophrenia, asenapine and olanzapine were similarly effective in reducing negative symptoms at week 26, with asenapine providing better results than olanzapine at week 52 in one of the extensions. The most frequently reported adverse events with asenapine are somnolence, akathisia and oral hypoesthesia. Although potentially associated with more extrapyramidal symptoms, asenapine appears to have less weight gain and metabolic effects than some other antipsychotic agents, such as olanzapine. PMID- 27356922 TI - [Not Available]. PMID- 27356923 TI - [Hiatal hernia with gastric necrosis]. PMID- 27356924 TI - [The medical dissertation in Germany : A quantitative analysis of promotion regulations in medical faculties]. AB - BACKGROUND: The medical dissertation represents an independently processed scientific project. In the field of medicine this has for many years displayed the basis for controversial discussions. The aim of the study presented here was to evaluate the prerequisites of all current promotion regulations in German medical faculties in order to develop a comparability on the basis of a scoring system. METHOD: An independent analysis of all promotion regulations from German medical faculties for the year 2014 was carried out according to 12 primary outcome measures and a scoring system. RESULTS: The average total score of promotion regulations at 37 German medical faculties was 57.2 points (SD +/-9.5) out of a possible 100 scoring points. The highest scores with 72-85 points were achieved by 3 faculties and 5 achieved scores of only 42-45 points. The range of the different criteria tested was broad. While the written thesis, the review process, the examination requirements as well as the grading of the thesis were defined in all regulations, the introduction into good clinical practice, knowledge of methodology as well as a check for plagiarism only seem to play minor roles. CONCLUSION: The promotion regulations at German medical faculties show a great variation using the scoring system presented here for the first time. Standardized federal promotion regulations might help to establish a structured transparency as well as a national equality of opportunity. PMID- 27356925 TI - [Individualized or standard approach to the abdomen : Currently available data]. AB - BACKGROUND: Every abdominal incision can lead to early (e. g. abdominal infection) and late complications (e. g. hernia). The correct incision is often important to have optimal access to the surgical area and to keep complications low. OBJECTIVE: An analysis of the recent literature was carried out to clarify which access routes have advantages over other types of incision. MATERIAL AND METHODS: A literature search was carried out in the following databases: Cochrane database of systematic reviews (CDSR), Cochrane library, Medline and PubMed. Systematic reviews and studies with large numbers of cases were used for the evaluation, whereas studies with small numbers of cases and case reports were not taken into account. RESULTS: Midline incisions are the first choice for acute and elective abdominal surgery because of a good view into and rapid access to the abdominal cavity. For large upper abdominal operations transverse incisions can be considered of equal value due to excellent exploration possibilities, e.g. of the liver and pancreas. 25 years after the introduction of laparoscopy, this technique has become established for cholecystectomy, fundoplication and bariatric surgery. For appendix and colon surgery laparoscopy has the advantage of being less traumatic, whereby postoperative pain and hospitalization are reduced but under circumstances longer operating times must be expected. The single incision laparoscopic surgery (SILS) technique is beneficial in cosmetic outcome; however, incisional hernias, prolonged operating times and higher complication rates are limiting factors for this technique. Natural orifice transluminal endoscopic surgery (NOTES) and atypical incisions are rarely used. PMID- 27356926 TI - One clinic's experience with carbon fiber orthoses in neuromuscular disease. AB - INTRODUCTION: The purpose of this study was to summarize our experience with off the-shelf anterior shell carbon fiber ankle-foot orthoses (CFAFOs) prescribed to adult neuromuscular patients in an outpatient clinic. METHODS: We studied ambulatory patients who were seen in Muscular Dystrophy Association or amyotrophic lateral sclerosis clinics between 2011 and 2014 and prescribed anterior shell CFAFOs. Charts were reviewed with attention to diagnosis, satisfaction with use, and reasons for acceptance or rejection. We included individuals who were currently using AFOs and those being prescribed AFOs for the first time. We were especially interested in reasons for acceptance or rejection of the orthosis. RESULTS: Two hundred eighty-three charts were reviewed. Of these, 109 of 123 (89%) patients were satisfied or extremely satisfied with the anterior shell CFAFOs, including 38 who had previously used other styles. CONCLUSION: Anterior shell CFAFOs should be considered for most neuromuscular patients with distal leg weakness. Muscle Nerve 55: 202-205, 2017. PMID- 27356927 TI - Electrochemiluminescence of graphitic carbon nitride and its application in ultrasensitive detection of lead(II) ions. AB - Graphitic carbon nitride (g-C3N4) materials with a layered structure have unusual physicochemical properties. Herein it was shown that g-C3N4 quantum dots (QDs) obtained through a thermal-chemical etching route exhibited attractive upconversion and electrochemiluminescence (ECL) properties. After modification on nanoporous gold (NPG) with a sponge-like porous structure, g-C3N4 QDs were employed to fabricate an ECL sensor for the determination of Pb(2+) using target dependent DNAzyme as the recognition unit. Moreover, magnetic reduced graphene oxide nanosheets (rGO) attached with Fe3O4 nanoparticles (rGO-Fe3O4) were obtained via a one-pot in situ reduction approach, and used as carriers of DNAzyme. To make full use of the unique magnetic property the prepared rGO-Fe3O4, a flow injection ECL detecting cell was designed using indium tin oxide (ITO) glass as working electrode. Due to the unique separation and enrichment properties of magnetic Fe3O4-rGO materials as well as wire-like conductivity of NPG, high sensitivity and selectivity for the determination of Pb(2+) in real water samples were achieved. This indicates that g-C3N4 has excellent anodic ECL performance in the presence of triethanolamine, and could be applied in real environmental samples analyses. Graphical Abstract Graphitic carbon nitride based electrochemiluminescence sensor for the sensitive monitor of lead(II) ions in real samples was constructed. PMID- 27356928 TI - Factors influencing the extraction of pharmaceuticals from sewage sludge and soil: an experimental design approach. AB - Pharmaceuticals can enter the environment when organic waste products are recycled on agricultural soils. The extraction of pharmaceuticals is a challenging step in their analysis. The very different extraction conditions proposed in the literature make the choice of the right method for multi-residue analysis difficult. This study aimed at evaluating, with experimental design methodology, the influence of the nature, pH and composition of the extraction medium on the extraction recovery of 14 pharmaceuticals, including 8 antibiotics, from soil and sewage sludge. Preliminary experimental designs showed that acetonitrile and citrate-phosphate buffer were the best extractants. Then, a response surface design demonstrated that many cross-product and squared terms had significant effects, explaining the shapes of the response surfaces. It also allowed optimising the pharmaceutical recoveries in soil and sludge. The optimal conditions were interpreted considering the ionisation states of the compounds, their solubility in the extraction medium and their interactions with the solid matrix. To perform the analysis, a compromise was made for each matrix. After a QuEChERS purification, the samples were analysed by online SPE-UHPLC-MS-MS. Both methods were simple and economical. They were validated with the accuracy profile methodology for soil and sludge and characterised for another type of soil, digested sludge and composted sludge. Trueness globally ranged between 80 and 120 % recovery, and inter- and intra-day precisions were globally below 20 % relative standard deviation. Various pharmaceuticals were present in environmental samples, with concentration levels ranging from a few micrograms per kilogramme up to thousands of micrograms per kilogramme. Graphical abstract Influence of the extraction medium on the extraction recovery of 14 pharmaceuticals. Influence of the ionisation state, the solubility and the interactions of pharmaceuticals with solid matrix. Analysis of different soils and organic waste products. PMID- 27356929 TI - Erratum to: Minimally invasive anterior chest wall lifting technique for thoracoscopic mediastinal approach. PMID- 27356930 TI - Accelerated visualization of selected intracranial arteries by cycled super selective arterial spin labeling. AB - OBJECTIVE: To accelerate super-selective arterial spin labeling (ASL) angiography by using a single control condition denoted as cycled super-selective arterial spin labeling. MATERIALS AND METHODS: A single non-selective control image is acquired that is shared by selective label images. Artery-selective imaging is possible by geometrically changing the position of the labeling focus to more than one artery of interest during measurement. The presented approach is compared to conventional super-selective imaging in terms of its labeling efficiency inside and outside the labeling focus using numerical simulations and in vivo measurements. Additionally, the signal-to-noise ratios of the images are compared to non-selective ASL angiography and analyzed using a two-way ANOVA test and calculating the Pearson's correlation coefficients. RESULTS: The results indicate that the labeling efficiency is not reduced within the labeled artery, but can increase as a function of distance to the artery of interest when compared to conventional super-selective ASL. In the final images, no statistically significant difference of image quality can be observed while the acquisition duration could be reduced when the major brain feeding arteries are being tagged. CONCLUSION: Using super-selective arterial spin labeling, a single non-selective control acquisition suffices for reconstructing selective angiograms of the cerebral vasculature, thereby accelerating image acquisition of the major intracranial arteries without notable loss of information. PMID- 27356931 TI - The Multiple Roles of XBP1 in Regulation of Glucose and Lipid Metabolism. AB - X-box binding protein1 (XBP1) especially exerts its fundamental effects in the cellular organelle endoplasmic reticulum (ER) via affecting three trans-membrane stress sensor proteins: PKRlike ER kinase (PERK), inositol-requiring enzyme 1(IRE1) and activating transcription factor 6(ATF6). At the center of XBP1's broad effects is its remarkable metabolic housekeeper function. XBP1 decreased glucose dysfunction via funneling its effects on improving insulin sensitivity and stimulating insulin secretion. However, XBP1 also yields its double-edged effects, driving the transformation from excess glucose to lipid, which is a key contribution to obesity and T2DM. In this review, we highlight the vital mechanism of XBP1 in manipulating glucose and lipid metabolism involved by multiple signaling pathways. PMID- 27356932 TI - Discovery of Novel Genes Mediating Glucose and Lipid Metabolisms. AB - Glucose and lipid are the major energy sources, and pivotal components of organic metabolism in mammals. Inappropriate diet directly influences the metabolic rate, and can alter the body's homeostasis. The underlying changes in energy storage and utilization would manifest as metabolic syndrome including obesity and high blood pressure, and high blood glucose, which are predisposing factors that significantly increase the risk for cardiovascular diseases and Type 2 Diabetes (T2D). Thus, it is essential to identify the genes that are involved in the process of glucose and lipid metabolism. Utilizing current advanced scientific methodology and technology, as well as computational resources has led to discovery of many novel genes with major roles in energy metabolism. In addition, many studies have focused on the functional analysis of the novel genes. Nowadays, uncovering the genes that are involved in glucose and lipid storage and utilization, as well as underlying pathways that regulate expression of those genes is an area of ongoing research. Here, we summarize the current research related to the novel genes regulating glucose and lipid metabolisms, which enable us to develop more efficient means of prevention and management of metabolic diseases such as T2D, obesity, high blood glucose, and hypertension. PMID- 27356933 TI - Maintenance of Gastrointestinal Glucose Homeostasis by the Gut-Brain Axis. AB - Gastrointestinal homeostasis is a dynamic balance under the interaction between the host, GI tract, nutrition and energy metabolism. Glucose is the main energy source in living cells. Thus, glucose metabolic disorders can impair normal cellular function and endanger organisms' health. Diseases that are associated with glucose metabolic disorders such as obesity, diabetes, hypertension, and other metabolic syndromes are in fact life threatening. Digestive system is responsible for food digestion and nutrient absorption. It is also involved in neuronal, immune, and endocrine pathways. In addition, the gut microbiota plays an essential role in initiating signal transduction, and communication between the enteric and central nervous system. Gut-brain axis is composed of enteric neural system, central neural system, and all the efferent and afferent neurons that are involved in signal transduction between the brain and gut-brain. Gut brain axis is influenced by the gut-microbiota as well as numerous neurotransmitters. Properly regulated gut-brain axis ensures normal digestion, absorption, energy production, and subsequently maintenance of glucose homeostasis. Understanding the underlying regulatory mechanisms of gut-brain axis involved in gluose homeostasis would enable us develop more efficient means of prevention and management of metabolic disease such as diabetic, obesity, and hypertension. PMID- 27356934 TI - From Histones to RNA: Role of Methylation in Signal Proteins Involved in Adipogenesis. AB - New fat cells originate from a preexisting population of undifferentiated progenitor cells named preadipocytes. The process in which preadipocytes proliferate and differentiate into mature adipocytes under certain circumstances is called adipogenesis. In the past decade, many epigenetic factors have been shown to be pivotal for the appropriate timing of adipogenesis. A large number of coregulators at critical gene promoters set up specific patterns of DNA methylation, histone methylation and RNA methylation, which act as an epigenetic code to modulate the correct progress of adipocyte differentiation and adipogenesis. In this review, we focus on the functions and roles of epigenetic processes in preadipocyte differentiation and adipogenesis. PMID- 27356935 TI - Nuclear Receptors in Hepatic Glucose and Lipid Metabolism During Neonatal and Adult Life. AB - Research efforts focusing on metabolic diseases have established a close conjunction between glucolipid abnormalities and nuclear receptors, a large superfamily of receptors including classic peroxisome proliferation-activated receptors (PPARs), liver X receptors (LXRs), farnesoid X receptors (FXRs) and glucocorticoid receptors (GRs) together with burgeoning retinoic acid receptor related orphan receptors (RORs) and REV-ERBs. Nuclear receptors are identified to control a series of physiological and pathological processes of glucose and lipid metabolism and also implicated to mediate the long-term effects of early environmental and nutritional experiences on the formation of adult chronic metabolic disorders in human and animals. Thus, nuclear receptors play profound roles in fetal programming and adult regulation of glucolipid metabolism. In this review, we provide an overview on the recent advances in the field of nuclear receptors focusing on their roles in lipid and glucose metabolism during early and late life courses. We hope that this knowledge may shed new lights on identifying the novel target molecules or pathways for the prevention and treatment of metabolic disorders involving disrupted glucose and lipid homeostasis in human and animals. PMID- 27356937 TI - Modulation of Protein Metabolism to Mitigate Nitrous Oxide (N2O) Emission from Excreta of Livestock. AB - Dietary protein is the main source of the body needed protein for animals. A great number of domestic animals including cattle, sheep, goats, pigs and chicken and other species are raised in the world to supply meat, milk and eggs that contain high quality of protein for human consumption. Domestic animals consume a great amount of feeds and water and excrete a large amount of faeces and urine. The conversion rate of dietary nitrogen (N, mainly dietary protein) to product N in livestock is low and the amount of N excretion is high and the nitrogenous compounds in excreta can be used as materials for nitrous oxide (N2O) formation in the processes of nitrification and denitrification in storage of excreta. Hence livestock farms and grazing pastures are important sources of N2O. N2O is a potent greenhouse gas and the key factor that damages the ozonosphere of the earth. Therefore, it is urgent to reveal the dietary protein metabolism processes and the regulation mechanism, which will help to reduce N2O emission. The nutritional options to reduce N excretion from livestock and consequently N2O emission include feeding low N rations and supplementing essential amino acid (AA) such as lysine and methionine to balance the AA profile of rations for pigs and ruminants. Other options include regulating partition of N excretion from urine to faeces and urinary nitrogenous constituents by decreasing urea N and increasing hippuric acid in ruminants. Supplementing tannic acid in the ration of ruminants has the potential to decrease the ratio of urinary N/faecal N and regulate the urinary nitrogenous components of ruminants and possibly reduce N2O emission in storage of excreta. PMID- 27356936 TI - "Bridge Proteins" Link Inflammation and Metabolic Diseases: Potential Targets for Therapeutics. AB - Clinical observations support the postulate that chronic low-grade inflammation underlies metabolic diseases and inflammatory mediators can trigger some metabolic diseases. In disorder condition, what is the first one: metabolic diseases cause inflammation or conversely? This "chicken or egg" type question was hard to answer. However, instead of focusing on this difficult issue, we should ask another challenging question: what are the links between inflammation and metabolic diseases? Seizing the key from this chaos may be the best way to solve the problem and break the cycle. To answer this question, we review the regulators (such as NF-kappaB, PPARs, mTOR, and STAT3) that have important roles in both metabolism and inflammation. These "bridge proteins" that link metabolic diseases and inflammation not only increase our understanding of these two diseases, but also provide potential targets for therapeutics and practical clinical applications. PMID- 27356938 TI - Protein Metabolism and Signal Pathway Regulation in Rumen and Mammary Gland. AB - Protein is an important yet the most expensive dietary component for farm ruminant animals. Understanding the mechanism behind protein utilization in animals for maintenance and milk production is critical for raising animals efficiently. Once the protein has been ingested, it undergoes various transformations in the gut before it is absorbed into blood and its precursors are harnessed by the mammary gland for milk protein synthesis in lactating animals. Several signaling pathways are involved both in absorption and in milk protein biosynthesis. Protein metabolism and signal pathway regulation in various tissues of ruminant are thus reviewed with emphasis on two particular tissues, the rumen and the mammary gland. PMID- 27356939 TI - L-Arginine Modulates Glucose and Lipid Metabolism in Obesity and Diabetes. AB - Type 2 diabetes has become a global public health problem affecting approximately 380 million people throughout the world. It can cause many complications and lead to greater mortality. At present, there is no available medicine for effectively preventing diabetes. L-arginine, a functional amino acid, the precursor of nitric oxide, plays a crucial role in maintenance, reproduction, growth, anti-aging and immunity for animals. Growing clinical evidence indicates that dietary L-arginine supplementation can reduce obesity, decrease arterial blood pressure, resist oxidation and normalize endothelial dysfunction to bring about remission of type 2 diabetes. The potential molecular mechanism may play a role in modulating glucose homeostasis, promoting lipolysis, maintaining hormone levels, ameliorating insulin resistance, and fetal programing in early stages. The possible signaling pathway of the beneficial effects of L-arginine likely involves L-arginine-nitric oxide pathway through which cell signal protein can be activated. Accumulating studies have indicated that L-arginine may have potential to prevent and/or relieve type 2 diabetes via restoring insulin sensitivity in vivo. PMID- 27356940 TI - Roles of Biogenic Amines in Intestinal Signaling. AB - Biogenic amines in the gastrointestinal tract are important metabolites of dietary protein and amino acids with the help of gut digestive enzymes and microbes, which play a crucial role in the regulation of intestinal functions, including digestion, absorption, and local immunity. However, high concentrations of biogenic amines can induce adverse reactions and are harmful to animal's health. Therefore, it is crucial to have a clear understanding of how different biogenic amines interact with a body's intestinal function signaling pathways and to monitor the content of biogenic amines in the gastrointestinal tract. And in turn, the proper concentration of dietary protein and balanced amino acids for humans and livestock could be given. Though numerous methods have been developed and improved for the detection of biogenic amines in foods or wines much less attention has been paid directly to the determination of amine levels in the gastrointestinal tract. In this article, we mainly focus on the interaction of amines with the intestinal function signaling pathway and the broad impacts on animal physiology, and our modified method to accurately and quickly detect the biogenic amines in the digesta of an animal intestine. PMID- 27356941 TI - AMPK Regulation of Glucose, Lipid and Protein Metabolism: Mechanisms and Nutritional Significance. AB - AMP-activated protein kianse (AMPK) is a master sensor of cellular energy levels and a crucial regulator of nutrient metabolism such as the synthesis of fatty acids, glucose and protein as well as their oxidation to CO2 and water . Thus, AMPK signaling has important implications for fat deposition and glucose homeostasis in animals and humans. Much experimental and clinical evidence show that AMPK is a key therapeutic target for the prevention of diseases such as obesity, diabetes, cancer, inflammation and cardiac dysfunction. In this review we highlight recent advances on the upstream and downstream targets of AMPK, as well as the specific mechanisms whereby AMPK regulates digestive functions and chronic energy balance in animals and humans. PMID- 27356942 TI - Heterologous Expression Systems for Plant Defensin Expression: Examples of Success and Pitfalls. AB - Defensins are a superfamily of antimicrobial peptides, present in vertebrates, invertebrates, fungi and plants, suggesting that they appeared prior to the divergence in eukaryotes. The destitution of toxicity to mammalian cells of plant defensins has led to a new research ground, i.e., their potential medical use against human infectious diseases. Isolating defensins from natural sources, like plant tissues, can be time-consuming, labor intensive and usually present low yields. Strategies for large-scale production of purified active defensins have been employed using heterologous expression systems (HES) for defensin production, usually based in E. coli system. Like any other technology, HES present limitations and drawbacks demanding a careful experimental design prior the system selection. This review is proposed to discuss some of the major concerns when choosing to heterologously express plant defensins, with special attention on bacterial expression systems. PMID- 27356943 TI - I'm a healthy patient; get me out of here. PMID- 27356944 TI - Effectiveness of backward walking training on walking ability in children with hemiparetic cerebral palsy: a randomized controlled trial. AB - OBJECTIVE: To compare the effects of backward walking training and forward walking training on spatiotemporal gait parameters, and gross motor function measures in children with cerebral palsy. DESIGN: Randomized controlled clinical trial. SETTING: Physical therapy clinics. SUBJECTS: A total of 30 children with hemiparetic cerebral palsy of both sexes (10 to 14 years of age, classified as I or II by gross motor function classification system) participated in this study. They were randomly assigned into two equal groups. INTERVENTIONS: Both groups received a conventional physical therapy program for 12 successive weeks (three sessions per week). The experimental group additionally received (25 min) backward walking training. The control group additionally received (25 min) forward walking training. OUTCOME MEASURES: Baseline, posttreatment, and follow up assessment for spatiotemporal gait parameters and gross motor functions were evaluated by using three dimensional gait analysis system and gross motor function measures. RESULTS: There was a significant improvement in step length, walking velocity, cadence, stance phase, and swing phase percentage and gross motor function measures (Dimensions D and E) of the experimental group (0.55 +/ 0.16, 0.53 +/-0.19, 121.73 +/-2.89, 54.73 +/-1.67, 44.40 +/-1.40, 90.20 +/-6.44, 82.47 +/-12.82), respectively, than the control group (0.39 +/-0.13, 0.46 +/ 0.20, 125.80 +/-2.96, 50.27 +/-1.62, 49.47 +/-1.55, 82.47 +/-7.05, 80.47 +/ 12.61), respectively, ( p < 0.05). The significant improvement of all measured outcomes of the experimental group was maintained at 1 month follow-up assessment ( p < 0.05). CONCLUSION: In addition to a conventional physical therapy program, backward walking training is more effective than forward walking training on spatiotemporal gait parameters, and gross motor function measures in children with hemiparetic cerebral palsy. PMID- 27356945 TI - Bivalirudin for Alternative Anticoagulation in Extracorporeal Membrane Oxygenation: A Systematic Review. AB - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) offers therapeutic options in refractory respiratory and/or cardiac failure. Systemic anticoagulation with heparin is routinely administered. However, in patients with heparin-induced thrombocytopenia or heparin resistance, the direct thrombin inhibitor bivalirudin is a valid option and has been increasingly used for ECMO anticoagulation. We aimed at evaluating its safety and its optimal dosing for ECMO. METHODS: Systematic web-based literature search of PubMed and EMBASE performed via National Health Service Library Evidence and manually, updated until January 30, 2016. RESULTS: The search revealed 8 publications relevant to the topic (5 case reports). In total, 58 patients (24 pediatrics) were reported (18 received heparin as control groups). Bivalirudin was used with or without loading dose, followed by infusion at different ranges (lowest 0.1-0.2 mg/kg/h without loading dose; highest 0.5 mg/kg/h after loading dose). The strategies for monitoring anticoagulation and optimal targets were dissimilar (activated partial thromboplastin time 45-60 seconds to 42-88 seconds; activated clotting time 180 200 seconds to 200-220 seconds; thromboelastography in 1 study). CONCLUSION: Bivalirudin loading dose was not always used; infusion range and anticoagulation targets were different. In this systematic review, we discuss the reasons for this variability. Larger studies are needed to establish the optimal approach with the use of bivalirudin for ECMO. PMID- 27356946 TI - Subplatysmal Necklift: A Retrospective Analysis of 504 Patients. AB - BACKGROUND: Improvement of neck contour is a primary goal of patients who seek rejuvenation of the face and neck. Subplatysmal structures, including fat, the digastric muscle, and the submandibular salivary glands (SMSGs), may contribute to the appearance of a disproportionately large neck. OBJECTIVES: The authors sought to evaluate the safety, effectiveness, and predictability of necklift combined with reshaping and repositioning of the subplatysmal structures. METHODS: The records of 504 patients were reviewed retrospectively. Surgical maneuvers for subplatysmal necklift were described comprehensively and supplemented with videos. The subplatysmal anatomy was detailed by means of 2 cadaver dissections. RESULTS: A total of 430 patients (85.3%) underwent subplatysmal necklift. The most commonly treated structures were fat (423 patients [83.9%]), the SMSGs (307 patients [60.9%]), and the digastric muscle (91 patients [18.1%]). The most common complications were weakness of the lower lip depressor (29 patients [5.7%]), followed by sialoma of the parotid gland (10 patients [2%]). No patients experienced subplatysmal hematoma. CONCLUSIONS: Subplatysmal necklift is a safe, effective, and reliable option for patients who desire improved cervical contour. LEVEL OF EVIDENCE: 4 Therapeutic. PMID- 27356947 TI - A variant of the CXCL11 gene may influence susceptibility to contact allergy, particularly in polysensitized patients. AB - BACKGROUND: Hereditary factors may influence individual susceptibility to contact allergy. OBJECTIVES: To investigate genetic variants with impacts on early inflammatory reactions and T cell functions that possibly increase the risk of contact allergy. PATIENTS AND METHODS: Three hundred and seventy two patients undergoing patch testing were recruited from the Information Network of Departments of Dermatology (IVDK). Of these, 133 were monosensitized and 239 were polysensitized, defined as reacting to three or more unrelated sensitizers. Within the polysensitized individuals, a subgroup with at least one particularly strong patch test reaction (strong reactors; n = 194) was considered. Three hundred and forty-seven blood bank donors served as controls. Fifteen genetic variants in 13 genes were analysed. RESULTS: The homozygous variant CXCL11 AA genotype (rs6817952) was significantly more frequent among polysensitized patients (10 of 239 = 4.2%; p = 0.0048; odds ratio 7.49; 95%CI: 1.7-36.1) than among monosensitized patients (2.2%) and in the control group (0.6%). None of the remaining genetic variants investigated were characterized by similarly strong associations. However, the significance was lost after correction for multiple comparisons. CONCLUSIONS: The homozygous variant CXCL11 genotype is associated with an increased risk of contact allergy. To confirm this exploratory finding, further independent studies are needed. PMID- 27356948 TI - Estimated probability of becoming a case of drug dependence in relation to duration of drug-taking experience: a functional analysis approach. AB - Measured as elapsed time from first use to dependence syndrome onset, the estimated "induction interval" for cocaine is thought to be short relative to the cannabis interval, but little is known about risk of becoming dependent during first months after onset of use. Virtually all published estimates for this facet of drug dependence epidemiology are from life histories elicited years after first use. To improve estimation, we turn to new month-wise data from nationally representative samples of newly incident drug users identified via probability sampling and confidential computer-assisted self-interviews for the United States National Surveys on Drug Use and Health, 2004-2013. Standardized modules assessed first and most recent use, and dependence syndromes, for each drug subtype. A four-parameter Hill function depicts the drug dependence transition for subgroups defined by units of elapsed time from first to most recent use, with an expectation of greater cocaine dependence transitions for cocaine versus cannabis. This study's novel estimates for cocaine users one month after first use show 2-4% with cocaine dependence; 12-17% are dependent when use has persisted. Corresponding cannabis estimates are 0-1% after one month, but 10-23% when use persists. Duration or persistence of cannabis smoking beyond an initial interval of a few months of use seems to be a signal of noteworthy risk for, or co-occurrence of, rapid-onset cannabis dependence, not too distant from cocaine estimates, when we sort newly incident users into subgroups defined by elapsed time from first to most recent use. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27356949 TI - Employment status among the Singapore elderly and its correlates. AB - AIM: It has been hypothesized that working beyond retirement age may have a protective effect on various aspects of well-being in the elderly. This paper aims to examine the relationship between employment status of elderly Singaporeans and indicators of well-being. METHODS: As part of the Well-being of the Singapore Elderly study, data relating to sociodemographics, social networks, medical history, physical activity, cognitive function, and disability were collected from 2534 participants aged 60 years and older. Participants included full-time workers (n = 483), part-time workers (n = 205), the unemployed (n = 32), homemakers (n = 808), and retirees (n = 1006). The data were analyzed by multiple logistic regression. RESULTS: Likelihood of being employed decreased with age, and employment was higher among men. Paid workers had significantly higher levels of physical activity, more extensive social networks, better cognitive function, less disability, and lower risk of dementia than retirees and homemakers. Paid workers had significantly lower chronic disease burden than retirees and rated their health to be better than retirees and the unemployed. CONCLUSIONS: These findings show that meaningful employment is associated with better psychological and physiological well-being among the elderly, highlighting the importance of studying likely protective effects of employment and creating employment opportunities for elderly Singaporeans. PMID- 27356950 TI - A dual chain chimeric antigen receptor (CAR) in the native antibody format for targeting immune cells towards cancer cells without the need of an scFv. AB - Adoptive cell therapy with chimeric antigen receptor (CAR)-modified T cells showed remarkable therapeutic efficacy in the treatment of leukaemia/lymphoma. However, the application to a variety of cancer entities is often constricted by the non-availability of a single chain antibody (scFv), which is usually the targeting domain in a CAR, while antibodies in the natural format are often available. To overcome the limitation, we designed a CAR that uses an antibody in its natural configuration for binding. Such CAR consists of two chains, the immunoglobulin light and heavy chain with their constant regions, whereby the heavy chain is anchored to the membrane and linked to an intracellular signalling domain for T-cell activation. The two chains form a stable heterodimer, a so called dual chain CAR (dcCAR), and bind with high affinity and in a specific manner to their cognate antigen. By specific binding, the dcCAR activates engineered T cells for the release of pro-inflammatory cytokines and for target cell lysis. We provide evidence by three examples that the dcCAR format is universally applicable and thereby broadens the CAR cell therapy towards a larger variety of targets for which an scFv antibody is not available. PMID- 27356952 TI - Association between intake of antioxidants and pancreatic cancer risk: a meta analysis. AB - We conducted a meta-analysis to systematically evaluate the association between antioxidants intake and pancreatic cancer risk. Relevant articles were retrieved from PUBMED and EMBASE databases and standard meta-analysis methods were applied. Finally a total of 18 studies were included. Comparing the highest with lowest categories, higher dietary intakes of selenium, vitamin C, vitamin E, beta carotene and beta-cryptoxanthin were significantly associated with reduced pancreatic cancer risk (for selenium, pooled OR = 0.47, 95%CI 0.26-0.85; for vitamin C, pooled OR = 0.68, 95%CI 0.57-0.80; for vitamin E, pooled OR = 0.70, 95%CI 0.62-0.81; for beta-carotene, pooled OR = 0.74, 95%CI 0.56-0.98; for beta cryptoxanthin, pooled OR = 0.70, 95%CI 0.56-0.88). Lycopene intake was marginally associated with pancreatic cancer risk (pooled OR = 0.85, 95%CI 0.73-1.00), while no significant association was observed for alpha-carotene, lutein and zeaxanthin. In summary, higher dietary intake of selenium, vitamin C, vitamin E, beta-carotene and beta-cryptoxanthin was inversely associated with pancreatic cancer risk. PMID- 27356951 TI - Therapeutic efficacy in a hemophilia B model using a biosynthetic mRNA liver depot system. AB - DNA-based gene therapy has considerable therapeutic potential, but the challenges associated with delivery continue to limit progress. Messenger RNA (mRNA) has the potential to provide for transient production of therapeutic proteins, without the need for nuclear delivery and without the risk of insertional mutagenesis. Here we describe the sustained delivery of therapeutic proteins in vivo in both rodents and non-human primates via nanoparticle-formulated mRNA. Nanoparticles formulated with lipids and lipid-like materials were developed for delivery of two separate mRNA transcripts encoding either human erythropoietin (hEPO) or factor IX (hFIX) protein. Dose-dependent protein production was observed for each mRNA construct. Upon delivery of hEPO mRNA in mice, serum EPO protein levels reached several orders of magnitude (>125 000-fold) over normal physiological values. Further, an increase in hematocrit (Hct) was established, demonstrating that the exogenous mRNA-derived protein maintained normal activity. The capacity of producing EPO in non-human primates via delivery of formulated mRNA was also demonstrated as elevated EPO protein levels were observed over a 72-h time course. Exemplifying the possible broad utility of mRNA drugs, therapeutically relevant amounts of human FIX (hFIX) protein were achieved upon a single intravenous dose of hFIX mRNA-loaded lipid nanoparticles in mice. In addition, therapeutic value was established within a hemophilia B (FIX knockout (KO)) mouse model by demonstrating a marked reduction in Hct loss following injury (incision) to FIX KO mice. PMID- 27356953 TI - Fluorine-Doped Antiperovskite Electrolyte for All-Solid-State Lithium-Ion Batteries. AB - A fluorine-doped antiperovskite Li-ion conductor Li2 (OH)X (X=Cl, Br) is shown to be a promising candidate for a solid electrolyte in an all-solid-state Li-ion rechargeable battery. Substitution of F(-) for OH(-) transforms orthorhombic Li2 OHCl to a room-temperature cubic phase, which shows electrochemical stability to 9 V versus Li(+) /Li and two orders of magnitude higher Li-ion conductivity than that of orthorhombic Li2 OHCl. An all-solid-state Li/LiFePO4 with F-doped Li2 OHCl as the solid electrolyte showed good cyclability and a high coulombic efficiency over 40 charge/discharge cycles. PMID- 27356954 TI - Evaluation of ferritin and transferrin binding to tau protein. AB - Tau protein is a neurodegeneration biomarker. Due to the high concentration of metal ions in the brain, the metallation of tau proteins and their catalytic role in reactive oxygen formation have been identified as a major biochemical pathway of neurodegeneration. High levels of iron ions have been detected in Alzheimer's disease brains. One of biological sources of iron ions are iron-rich proteins, such as transferrin or ferritin. However, the interactions between tau and these metallo-proteins have not been fully characterized. Here, the interactions between the longest form of full-length tau protein (tau441) with iron-rich proteins were detected using electrochemical impedance spectroscopy. Tau441 was immobilized on Au surface, via N-terminal (N-tau-Au film) or Cys-residues (Cys tau-Au film), and the charge-transfer resistance, Rct, was monitored prior and post ferritin or transferrin binding. Significant increase in Rct was observed post transferrin binding above 50MUgmL-1, but not ferritin regardless of concentration with N-tau-Au film. Additionally, the electrochemical trend was linear with respect to transferrin concentration. Electrochemical data indicated low binding by ferritin to N-tau-Au or Cys-tau-Au films. The interaction of apotransferrin or apoferritin with tau films was also evaluated. Electrochemical data may be pointing to the differences in protein binding modes by transferrin compared to ferritin as well as to importance of metal ions in protein-protein interactions. PMID- 27356955 TI - Decreased expression of Beclin-1 is significantly associated with a poor prognosis in oral tongue squamous cell carcinoma. AB - The autophagy-related gene Beclin-1 is critical in the regulation of tumourigenesis and progression, but its role in oral tongue squamous cell carcinoma (OTSCC) has not yet been reported. This study aimed to investigate Beclin-1 expression and its significance in OTSCC. Beclin-1 expression was assessed by reverse transcription-quantitative polymerase chain reaction or western blot analysis in 14 OTSCC tissues and matched adjacent noncancerous tissues as well as in 5 OTSCC cell lines and a normal tongue epithelial cell line. Beclin-1 protein expression was examined by immunohistochemistry in 133 OTSCC specimens, and the correlation between Beclin-1 expression and clinicopathological features was investigated. Furthermore, MTT and colony formation assays were performed to investigate the effect of Beclin-1 on the proliferation and clonogenicity of OTSCC cells. It was demonstrated that Beclin-1 expression was significantly decreased in the majority of the 14 OTSCC tissues and the 5 OTSCC cell lines relative to the matched non-cancerous tissues and the normal tongue epithelial cell line, respectively. Immunohistochemistry analysis revealed that decreased Beclin-1 expression was significantly correlated with poor differentiation, lymph node metastasis, advanced clinical tumour-node metastasis stage, and a poor prognosis in patients with OTSCC. The in vitro assays indicated that the overexpression of Beclin-1 significantly inhibits the proliferation and clonogenicity of OTSCC cells. These results demonstrate that Beclin-1 acts as a tumour suppressor in the development or progression of OTSCC and that Beclin-1 may represent a novel prognostic marker for patients with OTSCC. PMID- 27356956 TI - Assessment of polycaprolacton (PCL) nanocomposite scaffold compared with hydroxyapatite (HA) on healing of segmental femur bone defect in rabbits. AB - Segmental bone loss due to trauma, infection, and tumor resection and even non union results in the vast demand for replacement and restoration of the function of the lost bone. The objective of this study is to utilize novel inorganic organic nanocomposites for biomedical applications. Biodegradable implants have shown great promise for the repair of bone defects and have been commonly used as bone substitutes, which traditionally would be treated using metallic implants. In this study, 45 mature male New Zealand white rabbits 6-8 months and weighting 3-3.5 kg were examined. Rabbits were divided into three groups. Surgical procedures were done after an intramuscular injection of Ketamine 10% (ketamine hydrochloride, 50 mg/kg), Rompun 5% (xylazine, 5 mg/kg). Then an approximately 6 mm diameter - 5 mm cylinder bone defect was created in the femur of one of the hind limbs. After inducing the surgical wound, all rabbits were colored and randomly divided into three experimental groups of nine animals each: Group 1 received medical pure nanocomposite polycaprolactone (PCL) granules, Group 2 received hydroxyapatite and Group 3 was a control group with no treatment. Histopathological evaluation was performed on days 15, 30 and 45 after surgery. On day 45 after surgery, the quantity of newly formed lamellar bone in the healing site in PCL group was better than onward compared with HA and control groups. Finally, nanocomposite PCL granules exhibited a reproducible bone-healing potential. PMID- 27356958 TI - The importance of measurement invariance in neurocognitive ability testing. AB - OBJECTIVE: Neurocognitive test batteries such as recent editions of the Wechsler's Adult Intelligence Scale (WAIS-III/WAIS-IV) typically use nation-level population-based norms. The question is whether these batteries function in the same manner across different subgroups based on gender, age, educational background, socioeconomic status, ethnicity, mother tongue, or race. Here, the author argues that measurement invariance is a core issue in determining whether population-based norms are valid for different subgroups. METHOD: The author introduces measurement invariance, argues why it is an important topic of study, discusses why invariance might fail in cognitive ability testing, and reviews a dozen studies of invariance of commonly used neurocognitive test batteries. RESULTS: In over half of the reviewed studies, IQ batteries were not found to be measurement invariant across groups based on ethnicity, gender, educational background, cohort, or age. Apart from age and cohort, test manuals do not take such lack of invariance into account in computing full-scale IQ scores or normed domain scores. CONCLUSIONS: Measurement invariance is crucial for valid use of neurocognitive tests in clinical, educational, and professional practice. The appropriateness of population-based norms to particular subgroups should depend also on whether measurement invariance holds with respect to important subgroups. PMID- 27356957 TI - Early Cerebral Circulation Disturbance in Patients Suffering from Severe Traumatic Brain Injury (TBI): A Xenon CT and Perfusion CT Study. AB - Traumatic brain injury (TBI) is widely known to cause dynamic changes in cerebral blood flow (CBF). Ischemia is a common and deleterious secondary injury following TBI. Detecting early ischemia in TBI patients is important to prevent further advancement and deterioration of the brain tissue. The purpose of this study was to clarify the cerebral circulatory disturbance during the early phase and whether it can be used to predict patient outcome. A total of 90 patients with TBI underwent a xenon-computed tomography (Xe-CT) and subsequently perfusion CT to evaluate the cerebral circulation on days 1-3. We measured CBF using Xe-CT and mean transit time (MTT: the width between two inflection points [maximum upward slope and maximum downward slope from inflow to outflow of the contrast agent]) using perfusion CT and calculated the cerebral blood volume (CBV) using the AZ 7000W98 computer system. The relationships of the hemodynamic parameters CBF, MTT, and CBV to the Glasgow Coma Scale (GCS) score and the Glasgow Outcome Scale (GOS) score were examined. There were no significant differences in CBF, MTT, and CBV among GCS3-4, GCS5-6, and GCS7-8 groups. The patients with a favorable outcome (GR and MD) had significantly higher CBF and lower MTT than those with an unfavorable one (SD, VS, or D). The discriminant analysis of these parameters could predict patient outcome with a probability of 70.6%. During the early phase, CBF reduction and MTT prolongation might influence the clinical outcome of TBI. These parameters are helpful for evaluating the severity of cerebral circulatory disturbance and predicting the outcome of TBI patients. PMID- 27356960 TI - A versatile post-synthetic method on a solid support for the synthesis of RNA containing reduction-responsive modifications. AB - An original post-synthetic method on a solid support was developed to introduce various disulfide bond containing groups at the 2'-OH of oligoribonucleotides (RNAs). It is based on a thiol disulfide exchange reaction between several readily accessible alkyldisulfanyl-pyridine derivatives and 2'-O-acetylthiomethyl RNA in the presence of butylamine. By this strategy, diverse 2'-O alkyldithiomethyl RNAs were obtained. These modifications provided high nuclease resistance to RNA and were easily removed with glutathione treatment, thus featuring a potential use for siRNA prodrugs. PMID- 27356961 TI - Prevalence and cumulative 5-year incidence of chronic lymphocytic leukemia in the adult population in the Russian Federation and Ukraine: Data from the LEUKOSPECT study. AB - OBJECTIVES: LEUKOSPECT was a retrospective, multicenter, epidemiologic study carried out in Russia and Ukraine, aiming to assess the prevalence and cumulative 5-year incidence of chronic lymphocytic leukemia (CLL) in the adult population. METHODS: All data were collected manually from patient medical records at each of the study sites and from official censuses. CLL prevalence and incidence were determined from a count of CLL cases (previously diagnosed and new cases) in the population who made at least one clinic visit for CLL during the period from 1 January 2009 to 31 December 2013. RESULTS: The recorded cumulative 5-year incidence of CLL during the study ranged from 1.46 per 100 000 persons (95% CI: 0.85-2.34) in Yekaterinburg, Russia, to 4.34 per 100 000 persons (95% CI: 2.48 7.04) in Luhansk, Ukraine. In 2013, the lowest prevalence of CLL was also recorded in Yekaterinburg: 7.11 per 100 000 persons (95% CI: 5.67-8.81). This was approximately 3.1 times lower than in Luhansk (21.92 per 100 000 population; 95% CI: 17.38-27.28). CONCLUSION: The results of this study show diverse CLL incidence and prevalence patterns in the adult population of the Russian Federation and Ukraine. Authors propose a more comprehensive study with large region involvement to provide a more precise description of the incidence and prevalence of CLL in Eastern European countries and to better understand disparities reported versus the USA and other Western countries. PMID- 27356959 TI - Targeting choline phospholipid metabolism: GDPD5 and GDPD6 silencing decrease breast cancer cell proliferation, migration, and invasion. AB - Abnormal choline phospholipid metabolism is associated with oncogenesis and tumor progression. We have investigated the effects of targeting choline phospholipid metabolism by silencing two glycerophosphodiesterase genes, GDPD5 and GDPD6, using small interfering RNA (siRNA) in two breast cancer cell lines, MCF-7 and MDA-MB-231. Treatment with GDPD5 and GDPD6 siRNA resulted in significant increases in glycerophosphocholine (GPC) levels, and no change in the levels of phosphocholine or free choline, which further supports their role as GPC-specific regulators in breast cancer. The GPC levels were increased more than twofold during GDPD6 silencing, and marginally increased during GDPD5 silencing. DNA laddering was negative in both cell lines treated with GDPD5 and GDPD6 siRNA, indicating absence of apoptosis. Treatment with GDPD5 siRNA caused a decrease in cell viability in MCF-7 cells, while GDPD6 siRNA treatment had no effect on cell viability in either cell line. Decreased cell migration and invasion were observed in MDA-MB-231 cells treated with GDPD5 or GDPD6 siRNA, where a more pronounced reduction in cell migration and invasion was observed under GDPD5 siRNA treatment as compared with GDPD6 siRNA treatment. In conclusion, GDPD6 silencing increased the GPC levels in breast cancer cells more profoundly than GDPD5 silencing, while the effects of GDPD5 silencing on cell viability/proliferation, migration, and invasion were more severe than those of GDPD6 silencing. Our results suggest that silencing GDPD5 and GDPD6 alone or in combination may have potential as a new molecular targeting strategy for breast cancer treatment. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27356962 TI - Strategically Stunning: The Professional Motivations Behind the Lipstick Effect. AB - The phenomenon of increased desire for, and use of, appearance-enhancing items during times of economic recession has been termed the lipstick effect The motivation underlying this effect has been attributed to women's desires to enhance their attractiveness to financially stable partners (Hill, Rodeheffer, Griskevicius, Durante, & White, 2012). In the present research, we found evidence for our proposal that during times of economic recession, the heightened economic concern experienced by women translates into increased desire to use appearance enhancing items to both attract romantic partners and create a favorable impression of themselves in the workplace, as both strategies can help women become secure financially. We also found that women with high economic concern elect to improve their professional appearance more frequently than their romantic attractiveness, which suggests that their motivation to obtain resources through a job dominates their motivation to obtain resources through a partner. PMID- 27356963 TI - The Effect of Relative Encoding on Memory-Based Judgments. AB - Several models of judgment propose that people struggle with absolute judgments and instead represent options on the basis of their relative standing. This leads to a conundrum when people make judgments from memory: They may encode an option's ordinal rank relative to the surrounding options but later observe a different distribution of options. Do people update their representations when making judgments from memory, or do they maintain their representations based on the initial encoding? In three studies, we found that people making memory-based judgments rely on a stimulus's relative standing in the distribution at the time of encoding rather than attending to absolute quality or updating the stimulus's ordinal ranking in light of the distribution at the time of the later judgment. PMID- 27356964 TI - Use of 18F-FDG PET/CT for diagnosis of vascular graft infection with spread to sternum caused by Coxiella burnetii. PMID- 27356966 TI - An insight into the optical properties of a sub nanosize glutathione stabilized gold cluster. AB - In this study, gold quantum clusters with distinct fluorescence properties were developed and their structural and physical behaviour was evaluated. The clusters were prepared by etching gold nanoparticles with glutathione. Three different Au33 clusters with emission profiles in the NIR region and one blue emitting cluster, Au8 were developed by varying the geometrical arrangement of atoms within the cluster. These clusters having sizes in the range of 0.7 to 2 nm were synthesized by choosing different reaction temperatures from 0 degrees C to 70 degrees C and pH between 1.5 and 10. In the three cases, formation of self assembled atoms within the cluster and the corresponding changes in optical properties were observed. A detailed evaluation of the number of atoms and the core-ligand ratio using MALDI-MS and a change in the binding energy as seen in the XPS study confirmed this finding. The study demonstrates that the self assembly of atoms and their arrangement is an important factor in determining the characteristics of the cluster. In this communication, we put forward a new concept where the number of atoms and their arrangement within the clusters play a crucial role in tuning their optical properties. PMID- 27356965 TI - Leukotrienes in exhaled breath condensate and fractional exhaled nitric oxide in workers exposed to TiO2 nanoparticles. AB - Human health data regarding exposure to nanoparticles are extremely scarce and biomonitoring of exposure is lacking in spite of rodent pathological experimental data. Potential markers of the health-effects of engineered nanoparticles were examined in 30 workers exposed to TiO2 aerosol, 22 office employees of the same plant, and 45 unexposed controls. Leukotrienes (LT) B4, C4, E4, and D4 were analysed in the exhaled breath condensate (EBC) and urine via liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Fractional exhaled nitric oxide (FeNO) and spirometry was also measured. The median particle number concentration of the aerosol in the production ranged from 1.98 * 10(4) to 2.32 * 10(4) particles cm(-3); about 80% of the particles were <100 nm in diameter. Median total mass concentration varied between 0.4 and 0.65 mg m(-3). All LT levels in workers' EBC were elevated relative to the controls (p < 0.01). LTs in the EBC sample were correlated with titanium levels. Urinary LTs were not elevated in the workers and office employees. Office workers had higher LTB4 in EBC (p < 0.05), and higher levels of FeNO (p < 0.01). FeNO was higher in office employees with allergic diseases and was negatively correlated with smoking (p < 0.01). In spirometry significant impairment in the workers was seen only for %VCIN and %PEF (both p < 0.01). Multiple regression analysis confirmed a significant association between production of TiO2 and all cysteinyl LTs in EBC (p < 0.01) and impaired %VCIN and %PEF (both p < 0.01). LTB4 was also associated with smoking (p < 0.01). LT levels complemented our earlier findings of DNA, protein, and lipid damage in the EBC of workers with nanoTiO2 exposures. Cysteinyl LTs in EBC analysis suggest inflammation and potential fibrotic changes in the lungs; they may be helpful for monitoring the biological effect of (nano)TiO2 on workers. Spirometry was not sensitive enough. PMID- 27356967 TI - Structural changes of layered alkylsiloxanes during the reversible melting solidification process. AB - Through various in situ analyses, we have revealed the structural changes that occur during the reversible melting-solidification process of layered alkylsiloxanes (CnLSiloxanes) with carbon numbers (n) of 18 and 16. In situ high resolution solid-state (13)C nuclear magnetic resonance (NMR) analysis at controlled temperatures indicates drastic conformational changes of the long alkyl chains during the melting-solidification process. A (13)C NMR signal at 33 ppm, which shows the highest intensity at room temperature (RT), is assigned to an inner methylene group with an all-trans conformation. As the temperature increases, the 33-ppm signal intensity decreases while the signal intensity at 30.5 ppm simultaneously increases. The 30.5 ppm signal is assigned to an inner methylene group with a trans-gauche conformation. Subsequently, upon cooling, the signal at 33 ppm recovers, even after CnLSiloxanes have melted. In situ X-ray diffraction measurements at controlled temperatures reveal that the ordered arrangement of the long alkyl chains becomes disordered with elevating temperatures and reordered upon cooling to RT. In situ high-resolution solid state (29)Si NMR analysis shows that the melting-solidification process progresses without any structural change in siloxane sheets of the CnLSiloxanes. Thus, the in situ analyses show that disordering of the long alkyl chains causes the CnLSiloxanes to melt. Because the majority of long alkyl chains are packed again in the ordered arrangement with the all-trans conformation upon cooling, the CnLSiloxanes are reversibly solidified and the CnLSiloxane structure is recovered. PMID- 27356968 TI - Barriers and facilitators to health care seeking behaviours in pregnancy in rural communities of southern Mozambique. AB - BACKGROUND: In countries, such as Mozambique, where maternal mortality remains high, the greatest contribution of mortality comes from the poor and vulnerable communities, who frequently reside in remote and rural areas with limited access to health care services. This study aimed to understand women's health care seeking practices during pregnancy, taking into account the underlying social, cultural and structural barriers to accessing timely appropriate care in Maputo and Gaza Provinces, southern Mozambique. METHODS: This ethnographic study collected data through in-depth interviews and focus group discussions with women of reproductive age, including pregnant women, as well as household-level decision makers (partners, mothers and mothers-in-law), traditional healers, matrons, and primary health care providers. Data was analysed thematically using NVivo 10. RESULTS: Antenatal care was sought at the heath facility for the purpose of opening the antenatal record. Women without antenatal cards feared mistreatment during labour. Antenatal care was also sought to resolve discomforts, such as headaches, flu-like symptoms, body pain and backache. However, partners and husbands considered lower abdominal pain as the only symptom requiring care and discouraged women from revealing their pregnancy early in gestation. Health care providers for pregnant women often included those at the health facility, matrons, elders, traditional birth attendants, and community health workers. Although seeking care from traditional healers was discouraged during the antenatal period, they did provide services during pregnancy and after delivery. Besides household-level decision-makers, matrons, community health workers, and neighbours were key actors in the referral of pregnant women. The decision-making process may be delayed and particularly complex if an emergency occurs in their absence. Limited access to transport and money makes the decision making process to seek care at the health facility even more complex. CONCLUSIONS: Women do seek antenatal care at health facilities, despite the presence of other health care providers in the community. There are important factors that prevent timely care-seeking for obstetric emergencies and delivery. Unfamiliarity with warning signs, especially among partners, discouragement from revealing pregnancy early in gestation, complex and untimely decision-making processes, fear of mistreatment by health-care providers, lack of transport and financial constraints were the most commonly cited barriers. Women of reproductive age would benefit from community saving schemes for transport and medication, which in turn would improve their birth preparedness and emergency readiness; in addition, pregnancy follow-up should include key family members, and community-based health care providers should encourage prompt referrals to health facilities, when appropriate. TRIAL REGISTRATION: NCT01911494. PMID- 27356969 TI - Divergent activity of the gonadotropin-releasing hormone receptor gene promoter among genetic lines of pigs is partially conferred by nuclear factor (NF)-B, specificity protein (SP)1-like and GATA-4 binding sites. AB - BACKGROUND: Binding of gonadotropin-releasing hormone (GnRH) to its receptor (GnRHR) on gonadotropes within the anterior pituitary gland is essential to reproduction. In pigs, the GnRHR gene is also located near a genetic marker for ovulation rate, a primary determinant of prolificacy. We hypothesized that pituitary expression of the GnRHR gene is alternatively regulated in genetic strains with elevated ovulation rates (Chinese Meishan and Nebraska Index) vs. standard white crossbred swine (Control). METHODS: Luciferase reporter vectors containing 5118 bp of GnRHR gene promoter from either the Control, Index or Meishan swine lines were generated. Transient transfection of line-specific, full length, deletion and mutation constructs into gonadotrope-derived alphaT3-1 cells were performed to compare promoter activity and identify regions necessary for divergent regulation of the porcine GnRHR gene. Additionally, transcription factors that bind the GnRHR promoter from each line were identified with electrophoretic mobility shift assays (EMSA). RESULTS: Dramatic differences in luciferase activity among Control, Index and Meishan promoters (19-, 27- and 49 fold over promoterless control, respectively; P < 0.05) were established. A single bp substitution (-1690) within a previously identified upstream enhancer ( 1779/-1667) bound GATA-4 in the Meishan promoter and the p52/p65 subunits of nuclear factor (NF)-kappaB in the homologous Control/Index promoters. Transient transfection of vectors containing block replacement mutations of either the GATA 4 or NF-kappaB binding sites within the context of their native promoters resulted in a 50 and 60 % reduction of luciferase activity, respectively (P < 0.05). Furthermore, two single-bp substitutions in the Meishan compared to Control/Index promoters resulted in binding of the p52 and p65 subunits of NF kappaB and a specificity protein 1 (SP1)-like factor (-1235) as well as GATA-4 ( 845). Vectors containing the full-length Meishan promoter harboring individual mutations spanning these regions reduced luciferase activity by 25 and 20 %, respectively, compared to native sequence (P < 0.05). CONCLUSIONS: Elevated activity of the Meishan GnRHR gene promoter over Control/Index promoters in alphaT3-1 cells is partially due to three single nucleotide polymorphisms resulting in the unique binding of GATA-4 (-1690), the p52/p65 subunits of NF-kB in combination with a SP1-like factor (-1235), and GATA-4 (-845). PMID- 27356970 TI - Expansion of amphibian intronless interferons revises the paradigm for interferon evolution and functional diversity. AB - Interferons (IFNs) are key cytokines identified in vertebrates and evolutionary dominance of intronless IFN genes in amniotes is a signature event in IFN evolution. For the first time, we show that the emergence and expansion of intronless IFN genes is evident in amphibians, shown by 24-37 intronless IFN genes in each frog species. Amphibian IFNs represent a molecular complex more complicated than those in other vertebrate species, which revises the established model of IFN evolution to facilitate re-inspection of IFN molecular and functional diversity. We identified these intronless amphibian IFNs and their intron-containing progenitors, and functionally characterized constitutive and inductive expression and antimicrobial roles in infections caused by zoonotic pathogens, such as influenza viruses and Listeria monocytogenes. Amphibians, therefore, may serve as overlooked vectors/hosts for zoonotic pathogens, and the amphibian IFN system provides a model to study IFN evolution in molecular and functional diversity in coping with dramatic environmental changes during terrestrial adaption. PMID- 27356971 TI - Psychoactive pharmaceuticals at environmental concentrations induce in vitro gene expression associated with neurological disorders. AB - BACKGROUND: A number of researchers have speculated that neurological disorders are mostly due to the interaction of common susceptibility genes with environmental, epigenetic and stochastic factors. Genetic factors such as mutations, insertions, deletions and copy number variations (CNVs) are responsible for only a small subset of cases, suggesting unknown environmental contaminants play a role in triggering neurological disorders like idiopathic autism. Psychoactive pharmaceuticals have been considered as potential environmental contaminants as they are detected in the drinking water at very low concentrations. Preliminary studies in our laboratory identified gene sets associated with neuronal systems and human neurological disorders that were significantly enriched after treating fish brains with psychoactive pharmaceuticals at environmental concentrations. These gene expression inductions were associated with changes in fish behavior. Here, we tested the hypothesis that similar treatments would alter in vitro gene expression associated with neurological disorders (including autism) in human neuronal cells. We differentiated and treated human SK-N-SH neuroblastoma cells with a mixture (fluoxetine, carbamazepine and venlafaxine) and valproate (used as a positive control to induce autism-associated profiles), followed by transcriptome analysis with RNA-Seq approach. RESULTS: We found that psychoactive pharmaceuticals and valproate significantly altered neuronal gene sets associated with human neurological disorders (including autism-associated sets). Moreover, we observed that altered expression profiles in human cells were similar to gene expression profiles previously identified in fish brains. CONCLUSIONS: Psychoactive pharmaceuticals at environmental concentrations altered in vitro gene expression profiles of neuronal growth, development and regulation. These expression patterns were associated with potential neurological disorders including autism, suggested psychoactive pharmaceuticals at environmental concentrations might mimic, aggravate, or induce neurological disorders. PMID- 27356972 TI - Isolation of Cells Specialized in Anticancer Alkaloid Metabolism by Fluorescence Activated Cell Sorting. AB - Plant specialized metabolism often presents a complex cell-specific compartmentation essential to accomplish the biosynthesis of valuable plant natural products. Hence, the disclosure and potential manipulation of such pathways may depend on the capacity to isolate and characterize specific cell types. Catharanthus roseus is the source of several medicinal terpenoid indole alkaloids, including the low-level anticancer vinblastine and vincristine, for which the late biosynthetic steps occur in specialized mesophyll cells called idioblasts. Here, the optical, fluorescence, and alkaloid-accumulating properties of C. roseus leaf idioblasts are characterized, and a methodology for the isolation of idioblast protoplasts by fluorescence-activated cell sorting is established, taking advantage of the distinctive autofluorescence of these cells. This achievement represents a crucial step for the development of differential omic strategies leading to the identification of candidate genes putatively involved in the biosynthesis, pathway regulation, and transmembrane transport leading to the anticancer alkaloids from C. roseus. PMID- 27356974 TI - A Stilbenoid-Specific Prenyltransferase Utilizes Dimethylallyl Pyrophosphate from the Plastidic Terpenoid Pathway. AB - Prenylated stilbenoids synthesized in some legumes exhibit plant pathogen defense properties and pharmacological activities with potential benefits to human health. Despite their importance, the biosynthetic pathways of these compounds remain to be elucidated. Peanut (Arachis hypogaea) hairy root cultures produce a diverse array of prenylated stilbenoids upon treatment with elicitors. Using metabolic inhibitors of the plastidic and cytosolic isoprenoid biosynthetic pathways, we demonstrated that the prenyl moiety on the prenylated stilbenoids derives from a plastidic pathway. We further characterized, to our knowledge for the first time, a membrane-bound stilbenoid-specific prenyltransferase activity from the microsomal fraction of peanut hairy roots. This microsomal fraction derived resveratrol 4-dimethylallyl transferase utilizes 3,3-dimethylallyl pyrophosphate as a prenyl donor and prenylates resveratrol to form arachidin-2. It also prenylates pinosylvin to chiricanine A and piceatannol to arachidin-5, a prenylated stilbenoid identified, to our knowledge, for the first time in this study. This prenyltransferase exhibits strict substrate specificity for stilbenoids and does not prenylate flavanone, flavone, or isoflavone backbones, even though it shares several common features with flavonoid-specific prenyltransferases. PMID- 27356973 TI - The Potyviral P3 Protein Targets Eukaryotic Elongation Factor 1A to Promote the Unfolded Protein Response and Viral Pathogenesis. AB - The biochemical function of the potyviral P3 protein is not known, although it is known to regulate virus replication, movement, and pathogenesis. We show that P3, the putative virulence determinant of soybean mosaic virus (SMV), targets a component of the translation elongation complex in soybean. Eukaryotic elongation factor 1A (eEF1A), a well-known host factor in viral pathogenesis, is essential for SMV virulence and the associated unfolded protein response (UPR). Silencing GmEF1A inhibits accumulation of SMV and another ER-associated virus in soybean. Conversely, endoplasmic reticulum (ER) stress-inducing chemicals promote SMV accumulation in wild-type, but not GmEF1A-knockdown, plants. Knockdown of genes encoding the eEF1B isoform, which is important for eEF1A function in translation elongation, has similar effects on UPR and SMV resistance, suggesting a link to translation elongation. P3 and GmEF1A promote each other's nuclear localization, similar to the nuclear-cytoplasmic transport of eEF1A by the Human immunodeficiency virus 1 Nef protein. Our results suggest that P3 targets host elongation factors resulting in UPR, which in turn facilitates SMV replication and place eEF1A upstream of BiP in the ER stress response during pathogen infection. PMID- 27356976 TI - Dysnatremia in Relation to Frailty and Age in Community-dwelling Adults in the National Health and Nutrition Examination Survey. AB - Background: Frailty represents an age-related state of increased risk of adverse health outcomes, reflecting some combination of increased damage and compromised repair processes. Our objectives were to establish whether frailty is associated with dysnatremia (a deviation of serum sodium from normal values), to determine whether frailty explains the previously established association between age and dysnatremia and to assay the impact of each on mortality. Methods: The relationship between age, frailty, and dysnatremia was investigated across the adult life course in 8,911 respondents from the 2003-2004 and 2005-2006 cross sectional National Health and Nutrition Examination Survey, on whom both laboratory and mortality data were available. A frailty index (FI) was calculated for each respondent and related to dysnatremia (serum sodium values outside a 136 144 mmol/L reference range). Results: Dysnatremia was significantly related to both age and frailty; as the degree of frailty increased, so did the proportion with dysnatremia, for example, from 4.1% in those with FI less than 0.10, to 12.4% in those with FI 0.40 or more; p less than .001. Adjusted for frailty, the relationship between age and dysnatremia was no longer significant. In the age- and sex-adjusted Cox models, both frailty (hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 1.04-1.05 for every 0.01 increase in FI) and dysnatremia (HR: 1.85; 95% CI: 1.51-2.26) were significant predictors of mortality; when hyponatremia was separated from hypernatremia in the Cox models, hypernatremia wasn't significant, but only 41 participants were identified as hypernatremic. Conclusion: Increasing frailty is associated with dysnatremia and confounds the association between age and dysnatremia. PMID- 27356975 TI - Evolution of RLSB, a nuclear-encoded S1 domain RNA binding protein associated with post-transcriptional regulation of plastid-encoded rbcL mRNA in vascular plants. AB - BACKGROUND: RLSB, an S-1 domain RNA binding protein of Arabidopsis, selectively binds rbcL mRNA and co-localizes with Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) within chloroplasts of C3 and C4 plants. Previous studies using both Arabidopsis (C3) and maize (C4) suggest RLSB homologs are post transcriptional regulators of plastid-encoded rbcL mRNA. While RLSB accumulates in all Arabidopsis leaf chlorenchyma cells, in C4 leaves RLSB-like proteins accumulate only within Rubisco-containing bundle sheath chloroplasts of Kranz type species, and only within central compartment chloroplasts in the single cell C4 plant Bienertia. Our recent evidence implicates this mRNA binding protein as a primary determinant of rbcL expression, cellular localization/compartmentalization, and photosynthetic function in all multicellular green plants. This study addresses the hypothesis that RLSB is a highly conserved Rubisco regulatory factor that occurs in the chloroplasts all higher plants. RESULTS: Phylogenetic analysis has identified RLSB orthologs and paralogs in all major plant groups, from ancient liverworts to recent angiosperms. RLSB homologs were also identified in algae of the division Charophyta, a lineage closely related to land plants. RLSB-like sequences were not identified in any other algae, suggesting that it may be specific to the evolutionary line leading to land plants. The RLSB family occurs in single copy across most angiosperms, although a few species with two copies were identified, seemingly randomly distributed throughout the various taxa, although perhaps correlating in some cases with known ancient whole genome duplications. Monocots of the order Poales (Poaceae and Cyperaceae) were found to contain two copies, designated here as RLSB-a and RLSB-b, with only RLSB-a implicated in the regulation of rbcL across the maize developmental gradient. Analysis of microsynteny in angiosperms revealed high levels of conservation across eudicot species and for both paralogs in grasses, highlighting the possible importance of maintaining this gene and its surrounding genomic regions. CONCLUSIONS: Findings presented here indicate that the RLSB family originated as a unique gene in land plant evolution, perhaps in the common ancestor of charophytes and higher plants. Purifying selection has maintained this as a highly conserved single- or two-copy gene across most extant species, with several conserved gene duplications. Together with previous findings, this study suggests that RLSB has been sustained as an important regulatory protein throughout the course of land plant evolution. While only RLSB-a has been directly implicated in rbcL regulation in maize, RLSB b could have an overlapping function in the co-regulation of rbcL, or may have diverged as a regulator of one or more other plastid-encoded mRNAs. This analysis confirms that RLSB is an important and unique photosynthetic regulatory protein that has been continuously expressed in land plants as they emerged and diversified from their ancient common ancestor. PMID- 27356978 TI - Dietary Patterns and Incident Dementia in Elderly Japanese: The Ohsaki Cohort 2006 Study. AB - BACKGROUND: Although it has been speculated that the Japanese dietary pattern has a preventive effect against incident dementia, no reported study has yet investigated this issue. The present prospective cohort study investigated the association between dietary patterns and incident dementia in elderly Japanese subjects. METHODS: We analyzed follow-up data covering a 5.7-year period for 14,402 older adults (>=65 years) participating in a community-based, prospective cohort study. Three dietary patterns (Japanese pattern, animal food pattern, and high-dairy pattern) were derived using principal component analysis of the consumption of 39 food and beverage items assessed using a food frequency questionnaire. Data on incident dementia were retrieved from the public Long-term Care Insurance database. RESULTS: With 71,043 person-years of follow-up, incidence of dementia was 9.0%. The score for the Japanese dietary pattern was associated with a lower risk of incident dementia (hazard ratio of the highest quartile vs the lowest, 0.80; 95% confidence interval: 0.66-0.97; p-trend = .016). The animal food pattern and the high-dairy pattern showed no significant association with incident dementia. CONCLUSIONS: In this population of elderly Japanese individuals, the Japanese dietary pattern was associated with a decreased risk of incident dementia. PMID- 27356977 TI - Physical Performance Across the Adult Life Span: Correlates With Age and Physical Activity. AB - Background: A number of large-scale population studies have provided valuable information about physical performance in aged individuals; however, there is little information about trajectories of function and associations with age across the adult life span. We developed a mobility-focused physical performance screener designed to be appropriate for the adult life span. Methods: The physical performance battery includes measures of mobility, strength, endurance, and balance. Physical activity (PA) was assessed with accelerometry. We examined age-related trends in physical performance and PA, and the relationship between physical performance and PA across the age range (30-90+), by decade, in 775 participants enrolled in the study 2012-2014. Results: Physical performance was worse with increasing age decade. Although men performed better than women across all ages, the decrement by age group was similar between genders. Worsening physical performance was observed as early as the fifth decade for chair stands and balance and in the sixth decade for gait speed and aerobic endurance. The number and strength of significant associations between physical performance and PA increased with greater age: the greatest number of significant associations was seen in the 60-79 age groups, with fewer reported in the 30-59 and 80-90+ age groups. More PA was associated with better physical function. Conclusion: These results emphasize the importance of a life span approach to studies of function and aging. This work points to the need for a physical performance screener that spans across adulthood as a clinical tool for identifying functional decline. PMID- 27356979 TI - Optimized methods for extracting circulating small RNAs from long-term stored equine samples. AB - Circulating miRNAs in body fluids, particularly serum, are promising candidates for future routine biomarker profiling in various pathologic conditions in human and veterinary medicine. However, reliable standardized methods for miRNA extraction from equine serum and fresh or archived whole blood are sorely lacking. We systematically compared various miRNA extraction methods from serum and whole blood after short and long-term storage without addition of RNA stabilizing additives prior to freezing. Time of storage at room temperature prior to freezing did not affect miRNA quality in serum. Furthermore, we showed that miRNA of NGS-sufficient quality can be recovered from blood samples after >10 years of storage at -80 degrees C. This allows retrospective analyses of miRNAs from archived samples. PMID- 27356980 TI - The outcome of experimentally induced inclusion body hepatitis (IBH) by fowl aviadenoviruses (FAdVs) is crucially influenced by the genetic background of the host. AB - In the present study, inclusion body hepatitis (IBH) was experimentally induced by oral inoculation of two groups of specific pathogen-free (SPF) broilers and two groups of SPF layers at day-old with either a fowl aviadenovirus (FAdV)-D or a FAdV-E strain. A substantial variation in the degree of susceptibility was observed with mortalities of 100 and 96% in the FAdV-E and D infected SPF broiler groups, respectively, whereas in the groups of infected SPF layers mortalities of only 20 and 8% were noticed. Significant changes in clinical chemistry analytes of all infected birds together with histopathological lesions indicated impairment of liver and pancreas integrity and functions. Furthermore, significantly lower blood glucose concentrations were recorded at peak of infection in both inoculated SPF broiler groups, in comparison to the control group, corresponding to a hypoglycaemic status. High viral loads were determined in liver and pancreas of SPF broilers already at 4 days post-infection (dpi), in comparison to SPF layers, indicating a somewhat faster viral replication in the target organs. Overall, highest values were noticed in the pancreas of SPF broilers independent of the virus used for infection. The actual study provides new insights into the pathogenesis of IBH, a disease evolving to a metabolic disorder, to which SPF broilers were highly susceptible. Hence, this is the first study to report a significant higher susceptibility of SPF broiler chickens to experimentally induced IBH in direct comparison to SPF layers. PMID- 27356982 TI - Movement towards transdiagnostic psychotherapeutic practices for the affective disorders. AB - Evidence-based cognitive behavioural therapy (CBT) practices were first developed in the 1960s. Over the decades, refinements and alternative symptom foci resulted in the development of several CBT protocols/manuals for each of the many disorders, especially in the affective disorders. Although shown to be effective in highly trained providers, the proliferation of CBT protocols also has shown to demonstrate challenges in dissemination and implementation efforts due to the sheer number of CBT protocols and their related training requirements (eg, 6 months per protocol) and their related cost (eg, over US$2000 each; lost days/hours at work). To address these concerns, newer transdiagnostic CBT protocols have been developed to reduce the number of disorder-specific CBT protocols needed to treat patients with affective disorders. Transdiagnostic treatments are based on the notion that various disorder-specific CBT protocols contain important but overlapping treatment components that can be distilled into a single treatment and therefore address the symptoms and comorbidities across all of the disorders at once. 3 examples of transdiagnostic treatments include group CBT of anxiety, unified protocol for transdiagnostic treatment for emotional disorders and transdiagnostic behaviour therapy. Each transdiagnostic protocol is designed for a different set of disorders, contains a varied amount of CBT treatment components and is tested in different types of samples. However, together, these 3 transdiagnostic psychotherapies represent the future of CBT practice. PMID- 27356981 TI - High occurrence of Blastocystis sp. subtypes 1-3 and Giardia intestinalis assemblage B among patients in Zanzibar, Tanzania. AB - BACKGROUND: Blastocystis is a common intestinal parasite with worldwide distribution but the distribution of Blastocystis and its subtypes in East Africa is largely unknown. In this study, we investigate the distribution of Blastocystis subtypes in Zanzibar, Tanzania and report the prevalence of intestinal parasites using both molecular methods and microscopy. METHODS: Stool samples were collected from both diarrhoeic and non-diarrhoeic outpatients in Zanzibar. In addition to microscopy, real-time PCR for Blastocystis, Entamoeba histolytica and E. dispar, Giardia intestinalis, Cryptosporidium spp., and Dientamoeba fragilis was used. Blastocystis subtypes were determined by a conventional PCR followed by partial sequencing of the SSU-rRNA gene. Genetic assemblages of Giardia were determined by PCR with assemblage specific primers. RESULTS: Intestinal parasites were detected in 85 % of the 174 participants, with two or more parasites present in 56 %. Blastocystis sp. and Giardia intestinalis were the most common parasites, identified by PCR in 61 and 53 % of the stool samples respectively, but no correlation between carriage of Blastocystis and Giardia was found. The Blastocystis subtype distribution was ST1 34.0 %, ST2 26.4 %, ST3 25.5 %, ST7 0.9 %, and 13.2 % were positive only by qPCR (non-typable). The Giardia genetic assemblages identified were A 6.5 %, B 85 %, A + B 4.3 %, and non-typable 4.3 %. The detection rate with microscopy was substantially lower than with PCR, 20 % for Blastocystis and 13.8 % for Giardia. The prevalence of Blastocystis increased significantly with age while Giardia was most prevalent in children two to five years old. No correlation between diarrhoea and the identification of Giardia, Blastocystis, or their respective genetic subtypes could be shown and, as a possible indication of parasite load, the mean cycle threshold values in the qPCR for Giardia were equal in diarrhoeic and non diarrhoeic patients. CONCLUSIONS: Carriage of intestinal parasites was very common in the studied population in Zanzibar. The most commonly detected parasites, Blastocystis and Giardia, had different age distributions, possibly indicating differences in transmission routes, immunity, and/or other host factors for these two species. In the Blastocystis subtype analysis ST1-3 were common, but ST4, a subtype quite common in Europe, was completely absent, corroborating the geographical differences in subtype distributions previously reported. PMID- 27356983 TI - Reading Comprehension in Boys with ADHD: The Mediating Roles of Working Memory and Orthographic Conversion. AB - Reading comprehension difficulties in children with ADHD are well established; however, limited information exists concerning the cognitive mechanisms that contribute to these difficulties and the extent to which they interact with one another. The current study examines two broad cognitive processes known to be involved in children's reading comprehension abilities-(a) working memory (i.e., central executive processes [CE], phonological short-term memory [PH STM], and visuospatial short-term memory [VS STM]) and (b) orthographic conversion (i.e., conversion of visually presented text to a phonological code)-to elucidate their unique and interactive contribution to ADHD-related reading comprehension differences. Thirty-one boys with ADHD-combined type and 30 typically developing (TD) boys aged 8 to 12 years (M = 9.64, SD = 1.22) were administered multiple counterbalanced tasks assessing WM and orthographic conversion processes. Relative to TD boys, boys with ADHD exhibited significant deficits in PH STM (d = -0.70), VS STM (d = -0.92), CE (d = -1.58), and orthographic conversion (d = 0.93). Bias-corrected, bootstrapped mediation analyses revealed that CE and orthographic conversion processes modeled separately mediated ADHD-related reading comprehension differences partially, whereas PH STM and VS STM did not. CE and orthographic conversion modeled jointly mediated ADHD-related reading comprehension differences fully wherein orthographic conversion's large magnitude influence on reading comprehension occurred indirectly through CE's impact on the orthographic system. The findings suggest that adaptive cognitive interventions designed to improve reading-related outcomes in children with ADHD may benefit by including modules that train CE and orthographic conversion processes independently and interactively. PMID- 27356985 TI - [Grading of lung cancer]. AB - In comparison with other tumor entities there is no common generally accepted grading system for lung cancer with clearly defined criteria and clinical relevance. In the recent fourth edition of the World Health Organization (WHO) classification from 2015 of tumors of the lungs, pleura, thymus and heart, there is no generally applicable grading for pulmonary adenocarcinomas, squamous cell carcinomas or rarer forms of carcinoma. Since the new IASLC/ATS/ERS classification of adenocarcinomas published in 2011, 5 different subtypes with significantly different prognosis are proposed. This results in an architectural (histologic) grading, which is usually applied to resection specimens. For squamous cell carcinoma the number of different histological subtypes in the new WHO classification was reduced compared to earlier versions but without a common grading system. In recent publications nesting and budding were proposed as the main (histologic) criteria for a grading of squamous cell carcinomas. The grading of neuroendocrine tumors (NET) of the lungs in comparison with NET in other organs is presented in a separate article in this issue. Certain rare tumor types are high grade per definition: small cell, large cell and pleomorphic carcinomas, carcinosarcomas and pulmonary blastomas. In the future it is to be expected that these developments will be further refined, e. g. by adding further subtypes for adenocarcinomas and cytologic and/or nuclear criteria for adenocarcinoma and/or squamous cell carcinomas. PMID- 27356986 TI - Does Sexy Media Promote Teen Sex? A Meta-Analytic and Methodological Review. AB - Parents and policy makers are often concerned that sexy media (media depicting or discussing sexual encounters) may promote sexual behavior in young viewers. There has been some debate among scholars regarding whether such media promote sexual behaviors. It remains unclear to what extent sexy media is a risk factor for increased sexual behavior among youth. The current study employed a meta-analysis of 22 correlational and longitudinal studies of sexy media effects on teen sexual behavior (n = 22,172). Moderator analyses examined methodological and science culture issues such as citation bias. Results indicated the presence only of very weak effects. General media use did not correlate with sexual behaviors (r = 0.005), and sexy media use correlated only weakly with sexual behaviors (r = 0.082) once other factors had been controlled. Higher effects were seen for studies with citation bias, and lower effects when family environment is controlled. The impact of media on teen sexuality was minimal with effect sizes near to zero. PMID- 27356984 TI - Long-read sequencing and de novo assembly of a Chinese genome. AB - Short-read sequencing has enabled the de novo assembly of several individual human genomes, but with inherent limitations in characterizing repeat elements. Here we sequence a Chinese individual HX1 by single-molecule real-time (SMRT) long-read sequencing, construct a physical map by NanoChannel arrays and generate a de novo assembly of 2.93 Gb (contig N50: 8.3 Mb, scaffold N50: 22.0 Mb, including 39.3 Mb N-bases), together with 206 Mb of alternative haplotypes. The assembly fully or partially fills 274 (28.4%) N-gaps in the reference genome GRCh38. Comparison to GRCh38 reveals 12.8 Mb of HX1-specific sequences, including 4.1 Mb that are not present in previously reported Asian genomes. Furthermore, long-read sequencing of the transcriptome reveals novel spliced genes that are not annotated in GENCODE and are missed by short-read RNA-Seq. Our results imply that improved characterization of genome functional variation may require the use of a range of genomic technologies on diverse human populations. PMID- 27356987 TI - NMR backbone resonance assignment and solution secondary structure determination of human NSD1 and NSD2. AB - Proteins of the NSD family are histone-methyl transferases with critical functions in the regulation of chromatin structure and function. NSD1 and NSD2 are homologous proteins that function as epigenetic regulators of transcription through their abilities to catalyse histone methylation. Misregulation of NSD1 and NSD2 expression or mutations in their genes are linked to a number of human diseases such as Sotos syndrome, and cancers including acute myeloid leukemia, multiple myeloma, and lung cancer. The catalytic domain of both proteins contains a conserved SET domain which is involved in histone methylation. Here we report the backbone resonance assignments and secondary structure information of the catalytic domains of human NSD1 and NSD2. PMID- 27356988 TI - Chemical shift assignments and secondary structure prediction for Q4DY78, a conserved kinetoplastid-specific protein from Trypanosoma cruzi. AB - Trypanosoma cruzi, Trypanosma brucei and Leishmania spp. are kinetoplastid protozoa causative agents of Chagas disease, sleeping sickness and leishmaniasis, respectively, neglected tropical diseases estimated to infect millions of people worldwide. Their genome sequencing has revealed approximately 50 % of genes encoding hypothetical proteins of unknown function, opening possibilities for novel target identification and drug discovery. Q4DY78 is a putative essential protein from T. cruzi conserved in the related kinetoplastids and divergent from mammalian host proteins. Here we report the (1)H, (15)N, and (13)C chemical shift assignments and secondary structure analysis of the Q4DY78 protein as basis for NMR structure determination, functional analysis and drug screening. PMID- 27356989 TI - The PILI@Work Program: a translation of the diabetes prevention program to Native Hawaiian-serving worksites in Hawai'i. AB - A previously translated Diabetes Prevention Program Lifestyle Intervention (DPP LI) was adapted for delivery as a worksite-based intervention, called PILI@Work, to address obesity disparities in Native Hawaiians/Pacific Islanders. This study examined the effectiveness of PILI@Work and factors associated with weight loss at post-intervention. Overweight/obese employees of 15 Native Hawaiian-serving organizations received the 3-month component of PILI@Work. Assessments included weight, systolic/diastolic blood pressure, physical activity and functioning, fat intake, locus of weight control, social support, and self-efficacy. Weight, systolic/diastolic blood pressure, physical functioning, physical activity frequency, fat intake, family support, and eating self-efficacy improved from pre to post-intervention. Regression analysis indicated that worksite type, decreased diastolic blood pressure, increased physical activity, and more internalized locus of weight control were significantly associated with 3-month weight loss. PILI@Work initiated weight loss in Native Hawaiians/Pacific Islanders. DPP-LI translated to worksite settings and tailored for specific populations can be effective for addressing obesity. PMID- 27356990 TI - Implementation of collaborative goal setting for diabetes in community primary care. AB - Collaborative goal setting (CGS) is a cornerstone of diabetes self-management support, but little is known about its feasibility and effectiveness during routine care. The aim of this study was to evaluate the implementation of an existing CGS intervention when integrated by primary care staff. Using a mixed methods approach guided by the RE-AIM framework, intervention adoption, implementation, reach, and effectiveness were evaluated over 12 months. Three of four sites adopted the CGS intervention, in which 521 patients with type 2 diabetes (9-29 % of those targeted) received CGS. For those with suboptimal glycemic control (A1C >= 7.5 %), %A1C decreased by 1.1 for those receiving CGS (n = 204, p < 0.001) compared to 0.4 for a group who did not (n = 41, p = 0.23). Practice characteristics influenced adoption and implementation, while isolation of CGS from the remainder of clinical care likely influenced reach and effectiveness. CGS may benefit patients with diabetes, but a lack of integration by practice staff is a key barrier to overcome during implementation. PMID- 27356991 TI - The impact of behavioral and mental health risk assessments on goal setting in primary care. AB - Patient-centered health risk assessments (HRAs) that screen for unhealthy behaviors, prioritize concerns, and provide feedback may improve counseling, goal setting, and health. To evaluate the effectiveness of routinely administering a patient-centered HRA, My Own Health Report, for diet, exercise, smoking, alcohol, drug use, stress, depression, anxiety, and sleep, 18 primary care practices were randomized to ask patients to complete My Own Health Report (MOHR) before an office visit (intervention) or continue usual care (control). Intervention practice patients were more likely than control practice patients to be asked about each of eight risks (range of differences 5.3-15.8 %, p < 0.001), set goals for six risks (range of differences 3.8-16.6 %, p < 0.01), and improve five risks (range of differences 5.4-13.6 %, p < 0.01). Compared to controls, intervention patients felt clinicians cared more for them and showed more interest in their concerns. Patient-centered health risk assessments improve screening and goal setting.Trial RegistrationClinicaltrials.gov identifier: NCT01825746. PMID- 27356992 TI - Prioritizing multiple health behavior change research topics: expert opinions in behavior change science. AB - Multiple health behavior change (MHBC) approaches are understudied. The purpose of this study is to provide strategic MHBC research direction. This cross sectional study contacted participants through the Society of Behavioral Medicine email listservs and rated the importance of 24 MHBC research topics (1 = not at all important, 5 = extremely important) separately for general and underserved populations. Participants (n = 76) were 79 % female; 76 % White, 10 % Asian, 8 % African American, 5 % Hispanic, and 1 % Native Hawaiian/Pacific Islander. Top MHBC research priorities were predictors of behavior change and the sustainability, long-term effects, and dissemination/translation of interventions for both populations. Recruitment and retention of participants (t(68) = 2.17, p = 0.000), multi-behavioral indices (t(68) = 3.54, p = 0.001), and measurement burden (t(67) = 5.04, p = 0.001) were important for the underserved. Results identified the same top research priorities across populations. For the underserved, research should emphasize recruitment, retention, and measurement burden. PMID- 27356993 TI - Statistical methodologies to pool across multiple intervention studies. AB - Combining and analyzing data from heterogeneous randomized controlled trials of complex multiple-component intervention studies, or discussing them in a systematic review, is not straightforward. The present article describes certain issues to be considered when combining data across studies, based on discussions in an NIH-sponsored workshop on pooling issues across studies in consortia (see Belle et al. in Psychol Aging, 18(3):396-405, 2003). Several statistical methodologies are described and their advantages and limitations are explored. Whether weighting the different studies data differently, or via employing random effects, one must recognize that different pooling methodologies may yield different results. Pooling can be used for comprehensive exploratory analyses of data from RCTs and should not be viewed as replacing the standard analysis plan for each study. Pooling may help to identify intervention components that may be more effective especially for subsets of participants with certain behavioral characteristics. Pooling, when supported by statistical tests, can allow exploratory investigation of potential hypotheses and for the design of future interventions. PMID- 27356994 TI - Deconstructing interventions: approaches to studying behavior change techniques across obesity interventions. AB - Deconstructing interventions into the specific techniques that are used to change behavior represents a new frontier in behavioral intervention research. This paper considers opportunities and challenges in employing the Behavior Change Techniques Taxonomy (BCTTv1) developed by Michie and colleagues, to code the behavior change techniques (BCTs) across multiple interventions addressing obesity and capture dose received at the technique level. Numerous advantages were recognized for using a shared framework for intervention description. Coding interventions at levels of the social ecological framework beyond the individual level, separate coding for behavior change initiation vs. maintenance, fidelity of BCT delivery, accounting for BCTs mode of delivery, and tailoring BCTs, present both challenges and opportunities. Deconstructing interventions and identifying the dose required to positively impact health-related outcomes could enable important gains in intervention science. PMID- 27356995 TI - Overview of the obesity intervention taxonomy and pooled analysis working group. AB - The National Heart, Lung, and Blood Institute and the National Institutes of Health Office of Disease Prevention convened a meeting on August 29-30, 2013 entitled "Obesity Intervention Taxonomy and Pooled Analysis." The overarching goals of the meeting were to understand how to decompose interventions targeting behavior change, and in particular, those that focus on obesity and to combine data from groups of related intervention studies to supplement what can be learned from the individual studies. This paper summarizes the workshop recommendations and provides an overview of the two other papers that originated from the workshop and that address decomposition of behavioral change interventions and pooling of data across diverse studies within a consortium. PMID- 27356996 TI - Indoor tanning promotions on social media in six US cities #UVTanning #tanning. AB - There is no research investigating indoor tanning advertising on social media. We assessed the use of social media to promote indoor tanning. We subscribed to social media platforms in six US cities and content-analyzed promotional messages received. We captured 662 messages on Twitter and Facebook, through salon emails, and in daily deal coupons. Salon postings were most frequent on Twitter and Facebook, with an average of 2-3 postings per week. National chains posted more frequently than local businesses. Forty percent of messages were devoid of tanning content and included photos, jokes, or popular references. Thirty percent mentioned price reductions, and 28 % referenced an upcoming holiday. Sunless tanning (17 %) was promoted more often than ultraviolet tanning (9 %). Tanning salons actively use social media as a strategy for maintaining relationships with customers and offer pricing deals that promote loyalty and high-frequency tanning. PMID- 27356997 TI - Tanning bed burns reported on Twitter: over 15,000 in 2013. AB - Few surveillance tools exist for monitoring tanning bed injuries. Twitter data were examined to identify and describe reports of tanning bed-caused burns. Tweets sent in 2013 containing keywords for tanning bed use and burning were content analyzed to determine whether a burn caused by a tanning bed was described, and additional data on tanning behavior and burn characteristics were extracted. After content assessment, 15,178 (64 %) tweets were found to describe a tanning bed-caused burn. Sites most reportedly burnt were buttocks (n = 3117), face/head (n = 1020), and chest/breast (n = 546). Alarmingly, 200 burns to the eyes/eyelids were mentioned. A total of 456 tweets described burning >1 time from a tanning bed. A total of 211 tweets mentioned falling asleep inside the tanning bed. In 2013, over 15,000 tweets reported tanning bed-caused burns. Twitter data provides unique insight into tanning behaviors and injuries not captured through traditional public health surveillance. PMID- 27356998 TI - Interest in a Twitter-delivered weight loss program among women of childbearing age. AB - Weight management through the childbearing years is important, yet few women have access to efficacious weight loss programs. Online social network-delivered programs may increase reach and thus impact. The aim of this study was to gauge interest in a Twitter-based weight loss intervention among women of childbearing age and the feasibility of recruitment via Twitter. We recruited English-speaking women aged 18-45 years (N = 63) from Twitter to complete an anonymous online survey including open-ended questions about program advantages and concerns. Forty percent of participants were obese and 83 % were trying to lose weight. Eighty-one percent were interested in a Twitter-delivered weight loss program. Interest was high in all subgroups (62-100 %). Participants (59 %) cited program advantages, including convenience, support/accountability, and privacy. Concerns (59 %) included questions about privacy, support/accountability, engagement, efficacy, and technology barriers. Research is needed to develop and evaluate social media-delivered interventions, and to develop methods for recruiting participants directly from Twitter. PMID- 27356999 TI - Development and design of an intervention to improve physical activity in pregnant women using Text4baby. AB - Text4baby is a free, mobile health information service for pregnant and post partum women. This study aims to understand preferences of physical activity text messages (SMS), sequentially develop prototype SMS, and determine preferred dose of SMS to inform a future study utilizing Text4baby. This study had a user centered design with three phases: (1) literature review and interviews with pregnant women for development of prototype SMS, (2) interviews with health care professionals and pregnant women for prototype SMS feedback, and (3) survey to determine preferred dose of SMS. Data from interviews identified knowledge and support as major themes. Prototypes were developed (N = 14) and informed 168 SMS. Pregnant women (N = 326) thought three SMS/week were about right (50.2 %) and preferred three SMS/week throughout pregnancy (71.9 %). There is a need for opportunities for behavioral scientists to incorporate evidence-based practices within scalable interventions. As such, this research will inform utilization of Text4baby to potentially improve physical activity participation. PMID- 27357000 TI - Society of Behavioral Medicine (SBM) position statement: SBM supports the National Colorectal Cancer Roundtable's (NCCRT) call to action to reach 80 % colorectal cancer screening rates by 2018. AB - The Society of Behavioral Medicine (SBM) urges stakeholders to support the National Colorectal Cancer Roundtable's (NCCRT) initiative 80 % by 2018. Colorectal cancer (CRC) is largely preventable with early detection of pre cancerous polyps but CRC screening is underutilized, especially among the underserved. In response to low screening rates, this initiative sets an important goal of a population screening rate of 80 % in adults ages 50 and older by the year 2018. It is estimated that this screening rate could prevent more than 20,000 CRC deaths per year within 15 years. The initiative takes a multilevel approach to improving screening rates and includes recommendations for clinicians, health care organizations, insurers, policymakers, and researchers. PMID- 27357001 TI - Agile science: creating useful products for behavior change in the real world. AB - Evidence-based practice is important for behavioral interventions but there is debate on how best to support real-world behavior change. The purpose of this paper is to define products and a preliminary process for efficiently and adaptively creating and curating a knowledge base for behavior change for real world implementation. We look to evidence-based practice suggestions and draw parallels to software development. We argue to target three products: (1) the smallest, meaningful, self-contained, and repurposable behavior change modules of an intervention; (2) "computational models" that define the interaction between modules, individuals, and context; and (3) "personalization" algorithms, which are decision rules for intervention adaptation. The "agile science" process includes a generation phase whereby contender operational definitions and constructs of the three products are created and assessed for feasibility and an evaluation phase, whereby effect size estimates/casual inferences are created. The process emphasizes early-and-often sharing. If correct, agile science could enable a more robust knowledge base for behavior change. PMID- 27357002 TI - The Impact of Concomitant Left Ventricular Non-compaction with Congenital Heart Disease on Perioperative Outcomes. AB - Left ventricular non-compaction (LVNC) is a heterogeneous myocardial disorder characterized by prominent trabeculations and inter-trabecular recesses which may occur in association with congenital heart disease (CHD). To date, few studies have been performed to assess whether the concomitant diagnosis of LVNC affects the outcomes of CHD surgery. A retrospective review of patients with LVNC with CHD (LVNC-CHD), 0-5 years of age, was conducted. Patients with CHD without LVNC (CHD-only) and 0-5 years of age with similar diagnosis distribution were selected for comparison. Perioperative data, including CHD diagnosis, operative course, and postoperative complications were collected and compared between groups. LVNC CHD was diagnosed in 26 children. Of the 26 with LVNC-CHD, 20 underwent surgery and these patients were compared with 276 CHD-only controls. Median total length of stay in the hospital was 12.5 days (IQR 5.5-63 days) in LVNC-CHD compared to 5 days (IQR 3-10 days) in CHD-only (p < 0.005). Postoperative death, cardiac arrest, or need for ECMO or transplantation occurred in 6/20 (30 %) of the LVNC CHD patients compared to 3/276 (1 %) of the CHD-only group (p < 0.0001). LVNC-CHD patients had significantly longer hospital length of stay and higher perioperative complications compared to CHD-only patients without myocardial abnormalities. Pediatric cardiac care teams should be cognizant of the possibility of the increased perioperative risk associated with concomitant LVNC. Future prospective studies are warranted. PMID- 27357004 TI - Growth of Co2FeAl Heusler alloy thin films on Si(100) having very small Gilbert damping by Ion beam sputtering. AB - The influence of growth temperature Ts (300-773 K) on the structural phase ordering, static and dynamic magnetization behaviour has been investigated in ion beam sputtered full Heusler alloy Co2FeAl (CFA) thin films on industrially important Si(100) substrate. The B2 type magnetic ordering is established in these films based on the clear observation of the (200) diffraction peak. These ion beam sputtered CFA films possess very small surface roughness of the order of subatomic dimensions (<3 A) as determined from the fitting of XRR spectra and also by AFM imaging. This is supported by the occurrence of distinct Kiessig fringes spanning over the whole scanning range (~4 degrees ) in the x-ray reflectivity (XRR) spectra. The Gilbert damping constant alpha and effective magnetization 4piMeff are found to vary from 0.0053 +/- 0.0002 to 0.0015 +/- 0.0001 and 13.45 +/- 00.03 kG to 14.03 +/- 0.04 kG, respectively. These Co2FeAl films possess saturation magnetization ranging from 4.82 +/- 0.09 to 5.22 +/- 0.10 MUB/f.u. consistent with the bulk L21-type ordering. A record low alpha value of 0.0015 is obtained for Co2FeAl films deposited on Si substrate at Ts ~ 573 K. PMID- 27357003 TI - CSF Tau proteins reduce misdiagnosis of sporadic Creutzfeldt-Jakob disease suspected cases with inconclusive 14-3-3 result. AB - Cerebrospinal fluid (CSF) 14-3-3 protein supports sporadic Creutzfeldt-Jakob (sCJD) diagnosis, but often leads to weak-positive results and lacks standardization. In this study, we explored the added diagnostic value of Total Tau (t-Tau) and phosphorylated Tau (p-Tau) in sCJD diagnosis, particularly in the cases with inconclusive 14-3-3 result. 95 definite sCJD and 287 patients without prion disease (non-CJD) were included in this study. CSF samples were collected in routine clinical diagnosis and analysed for 14-3-3 detection by Western blot (WB). CSF t-Tau and p-Tau were quantified by commercial ELISA kits and PRNP and APOE genotyping assessed by PCR-RFLP. In a regression analysis of the whole cohort, 14-3-3 protein revealed an overall accuracy of 82 % (sensitivity = 96.7 %; specificity = 75.6 %) for sCJD. Regarding 14-3-3 clear positive results, we observed no added value either of t-Tau alone or p-Tau/t-Tau ratio in the model. On the other hand, considering 14-3-3 weak-positive cases, t-Tau protein increased the overall accuracy of 14-3-3 alone from 91 to 94 % and specificity from 74 to 93 % (p < 0.05), with no sensitivity improvement. However, inclusion of p-Tau/t-Tau ratio did not significantly improve the first model (p = 0.0595). Globally, t-Tau protein allowed a further discrimination of 65 % within 14-3-3 inconclusive results. Furthermore, PRNP MV genotype showed a trend to decrease 14 3-3 sensitivity (p = 0.051), but such effect was not seen on t-Tau protein. In light of these results, we suggest that t-Tau protein assay is of significant importance as a second marker in identifying 14-3-3 false-positive results among sCJD probable cases. PMID- 27357005 TI - Soil bacterial endemism and potential functional redundancy in natural broadleaf forest along a latitudinal gradient. AB - Microorganisms play key roles in ecosystem processes and biogeochemical cycling, however, the relationship between soil microbial taxa diversity and their function in natural ecosystems is largely unknown. To determine how soil bacteria community and function are linked from the local to regional scale, we studied soil bacteria community composition, potential function and environmental conditions in natural and mature broadleaf forests along a latitudinal gradient in China, using the Illumina 16S rRNA sequencing and GeoChip technologies. The results showed strong biogeographic endemism pattern in soil bacteria were existed, and the spatial distance and climatic variables were the key controlling factors for this pattern. Therefore, dispersal limitation and environmental selection may represent two key processes in generating and maintaining the soil bacterial biogeographic pattern. By contrast, the soil bacterial potential function is highly convergent along the latitudinal gradient and there were highly differing bacterial community compositions, and the soil chemistry may include the main factors active in shaping the soil bacterial potential function. Therefore, the soil bacterial potential function may be affected by local gradients in resource availability, and predicting soil bacterial potential function requires knowledge of abiotic and biotic environmental factors. PMID- 27357006 TI - Flexible Lamination-Fabricated Ultra-High Frequency Diodes Based on Self Supporting Semiconducting Composite Film of Silicon Micro-Particles and Nano Fibrillated Cellulose. AB - Low cost and flexible devices such as wearable electronics, e-labels and distributed sensors will make the future "internet of things" viable. To power and communicate with such systems, high frequency rectifiers are crucial components. We present a simple method to manufacture flexible diodes, operating at GHz frequencies, based on self-adhesive composite films of silicon micro particles (Si-MUPs) and glycerol dispersed in nanofibrillated cellulose (NFC). NFC, Si-MUPs and glycerol are mixed in a water suspension, forming a self supporting nanocellulose-silicon composite film after drying. This film is cut and laminated between a flexible pre-patterned Al bottom electrode and a conductive Ni-coated carbon tape top contact. A Schottky junction is established between the Al electrode and the Si-MUPs. The resulting flexible diodes show current levels on the order of mA for an area of 2 mm(2), a current rectification ratio up to 4 * 10(3) between 1 and 2 V bias and a cut-off frequency of 1.8 GHz. Energy harvesting experiments have been demonstrated using resistors as the load at 900 MHz and 1.8 GHz. The diode stack can be delaminated away from the Al electrode and then later on be transferred and reconfigured to another substrate. This provides us with reconfigurable GHz-operating diode circuits. PMID- 27357007 TI - Megakaryocytes regulate the quiescence of hematopoietic stem cells through PF4: 2013 ASH meeting highlights. AB - Hematopoietic stem cells (HSCs) can take one of the three different pathways: quiescence, self-renewal and differentiation. Mechanisms that control the tight balance to maintain lifelong hematopoietic homeostasis have been a major interest of research. Platelet factor-4 (PF4), a weak chemokine, is synthesized exclusively by megakaryocytes and sequestered in platelets. This meeting report highlights a novel study presented at 2013 ASH annual meeting. This study found that megakaryocyte, a progeny of HSC, was involved in maintaining quiescence of HSCs via PF4 in a feedback loop. PMID- 27357009 TI - Biomarker search illuminates cancer immune biology. PMID- 27357008 TI - Manganese Phosphate Self-assembled Nanoparticle Surface and Its application for Superoxide Anion Detection. AB - Quantitative analysis of superoxide anion (O2(.-)) has increasing importance considering its potential damages to organism. Herein, a novel Mn-superoxide dismutase (MnSOD) mimics, silica-manganous phosphate (SiO2-Mn3(PO4)2) nanoparticles, were designed and synthesized by surface self-assembly processes that occur on the surface of silica-phytic acid (SiO2-PA) nanoparticles. The composite nanoparticles were characterized by fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electronic microscopy (SEM), electron diffraction pattern, energy dispersive spectroscopy (EDS) and elemental mapping. Then the electrochemical measurements of O2(.-) based on the incorporation of SiO2-Mn3(PO4)2 onto the surface of electrodes were performed, and some satisfactory results were obtained. This is the first report that manganous phosphate (Mn3(PO4)2) nanoparticles with shape-controlled, but not multilayer sheets, were utilized for O2(.-) detection. The surface self-assembly technology we proposed will offer the ideal material to construct more types biosensor and catalytic system for its nanosized effect. PMID- 27357010 TI - Two pioneering osteoporosis drugs finally approach approval. PMID- 27357011 TI - EMA provides first glimpse of PRIME candidates. PMID- 27357012 TI - Parsing clinical success rates. PMID- 27357013 TI - Biotech R&D spend jumps by more than 15. PMID- 27357014 TI - Patent Watch: Nanomedicine patents highlight importance of production methods. PMID- 27357015 TI - Cancer: Bivalent mTOR inhibitors - the next generation. PMID- 27357016 TI - Blood diseases: Immunotoxins till the soil for stem cell transplantation. PMID- 27357017 TI - Anticancer drugs: Brain metastasis bridges the gap. PMID- 27357018 TI - Alzheimer disease: Antimicrobial role of amyloid-beta. PMID- 27357019 TI - Autoimmune disease: Reversing systemic lupus erythematosus. PMID- 27357020 TI - Depression: Understanding ketamine action. PMID- 27357021 TI - Successful treatment of hypertrophic lichen planus with betamethasone under occlusion and TCA-peelings. AB - Hypertrophic lichen planus (HLP) is a variant of lichen planus characterized by marked epidermal hyperplasia and severe pruritus. We present a case of a female patient with HLP and concomitant primary biliary cirrhosis, which responded to topical therapy with betamethasone under occlusion and TCA-peelings. PMID- 27357022 TI - Global Meningococcal Initiative: guidelines for diagnosis and confirmation of invasive meningococcal disease. AB - The Global Meningococcal Initiative (GMI) is an international group of scientists and clinicians with recognized expertise in meningococcal disease including microbiology, immunology, epidemiology, public health and vaccinology. The GMI was established to promote the global prevention of meningococcal disease through education, research and international cooperation. The GMI held its second summit meeting in 2013 to discuss the different aspects of existing meningococcal immunization programmes and surveillance systems. Laboratory confirmation and characterization were identified as essential for informing evidence-based vaccine implementation decisions. The relative merits of different confirmatory methodologies and their applications in different resource settings were a key component of the discussions. This paper summarizes the salient issues discussed, with special emphasis on the recommendations made and any deficiencies that were identified. PMID- 27357023 TI - Efficient [(18)F]AlF Radiolabeling of ZHER3:8698 Affibody Molecule for Imaging of HER3 Positive Tumors. AB - The human epidermal growth factor receptor 3 (HER3) is overexpressed in several cancers, being linked to a more resistant phenotype and hence leading to poor patient prognosis. Imaging HER3 is challenging owing to the modest receptor number (<50000 receptors/cell) in overexpressing cancer cells. Therefore, to image HER3 in vivo, high target affinity PET probes need to be developed. This work describes two different [(18)F]AlF radiolabeling strategies of the ZHER3:8698 affibody molecule specifically targeting HER3. The one-pot radiolabeling of ZHER3:8698 performed at 100 degrees C and using 1,4,7 triazanonane-1,4,7-triacetate (NOTA) as chelator resulted in radiolabeled products with variable purity attributed to radioconjugate thermolysis. An alternative approach based on the inverse electron demand Diels-Alder (IEDDA) reaction between a novel tetrazine functionalized 1,4,7-triazacyclononane-1,4 diacetate (NODA) chelator and the trans-cyclooctene (TCO) functionalized affibody molecule was also investigated. This method enabled the radiolabeling of the protein at room temperature. The [(18)F]AlF-NOTA-ZHER3:8698 and [(18)F]AlF-NODA ZHER3:8698 conjugates showed a specific uptake at 1 h after injection in high HER3-expressing MCF-7 tumors of 4.36 +/- 0.92% ID/g and 4.96 +/- 0.65% ID/g, respectively. The current results are encouraging for further investigation of [(18)F]AlF-NOTA-ZHER3:8698 as a HER3 imaging agent. PMID- 27357025 TI - Protein kinase C alpha is involved in the regulation of AXL receptor tyrosine kinase expression in triple-negative breast cancer cells. AB - AXL receptor tyrosine kinase is overexpressed in triple-negative breast cancer (TNBC), and has a function in cancer progression and metastases. However, the mechanism underlying AXL gene regulation in TNBC remains unknown. In this study, the involvement of protein kinase C alpha (PKCalpha) in the expression of AXL was investigated in human TNBC cells. The microarray data from other studies showed that PKCalpha is significantly correlated with AXL expression in TNBC cell lines. Tissue array analysis also confirmed their correlation in TNBC. The PKCalpha inhibitor Go6976 was used to treat MDA-MB-231 and Hs578T TNBC cells, which resulted in decreased expression of AXL and epithelia-mesenchymal transition related gene vimentin, and decreased cell proliferation. An MZF-1 acidic domain fragment (MZF-1 peptide), which was designed to downregulate PKCalpha expression, was transfected into the cells and resulted in inhibition of AXL expression. This effect was reversed by co-treatment with the constitutive form of PKCalpha. Moreover, the downregulation of PKCalpha was also confirmed by treatment with TAT fused MZF-1 peptide. Thus, the current study proposes that AXL may be correlated with PKCalpha-dependent TNBC cells, and could be modulated by MZF-1 peptides. PMID- 27357026 TI - Listeria monocytogenes in Retail Delicatessens: An Interagency Risk Assessment Risk Mitigations. AB - Cross-contamination, improper holding temperatures, and insufficient sanitary practices are known retail practices that may lead to product contamination and growth of Listeria monocytogenes. However, the relative importance of control options to mitigate the risk of invasive listeriosis from ready-to-eat (RTE) products sliced or prepared at retail is not well understood. This study illustrates the utility of a quantitative risk assessment model described in a first article of this series (Pouillot, R., D. Gallagher, J. Tang, K. Hoelzer, J. Kause, and S. B. Dennis, J. Food Prot. 78:134-145, 2015) to evaluate the public health impact associated with changes in retail deli practices and interventions. Twenty-two mitigation scenarios were modeled and evaluated under six different baseline conditions. These scenarios were related to sanitation, worker behavior, use of growth inhibitors, cross-contamination, storage temperature control, and reduction of the level of L. monocytogenes on incoming RTE food products. The mean risk per serving of RTE products obtained under these scenarios was then compared with the risk estimated in the baseline condition. Some risk mitigations had a consistent impact on the predicted listeriosis risk in all baseline conditions (e.g. presence or absence of growth inhibitor), whereas others were greatly dependent on the initial baseline conditions or practices in the deli (e.g. preslicing of products). Overall, the control of the bacterial growth and the control of contamination at its source were major factors of listeriosis risk in these settings. Although control of cross-contamination and continued sanitation were also important, the decrease in the predicted risk was not amenable to a simple solution. Findings from these predictive scenario analyses are intended to encourage improvements to retail food safety practices and mitigation strategies to control L. monocytogenes in RTE foods more effectively and to demonstrate the utility of quantitative risk assessment models to inform risk management decisions. PMID- 27357024 TI - Use of glucosamine and chondroitin supplements in relation to risk of colorectal cancer: Results from the Nurses' Health Study and Health Professionals follow-up study. AB - Recent epidemiologic evidence has emerged to suggest that use of glucosamine and chondroitin supplements may be associated with reduced risk of colorectal cancer (CRC). We therefore evaluated the association between use of these non-vitamin, non-mineral supplements and risk of CRC in two prospective cohorts, the Nurses' Health Study and Health Professionals Follow-up Study. Regular use of glucosamine and chondroitin was first assessed in 2002 and participants were followed until 2010, over which time 672 CRC cases occurred. Cox proportional hazards regression was used to estimate relative risks (RRs) within each cohort, and results were pooled using a random effects meta-analysis. Associations were comparable across cohorts, with a RR of 0.79 (95% CI: 0.63-1.00) observed for any use of glucosamine and a RR of 0.77 (95% CI: 0.59-1.01) observed for any use of chondroitin. Use of glucosamine in the absence of chondroitin was not associated with risk of CRC, whereas use of glucosamine + chondroitin was significantly associated with risk (RR: 0.77; 95% CI: 0.58-0.999). The association between use of glucosamine + chondroitin and risk of CRC did not change markedly when accounting for change in exposure status over follow-up (RR: 0.75; 95% CI: 0.58 0.96), nor did the association significantly vary by sex, aspirin use, body mass index, or physical activity. The association was comparable for cancers of the colon and rectum. Results support a protective association between use of glucosamine and chondroitin and risk of CRC. Further study is needed to better understand the chemopreventive potential of these supplements. PMID- 27357027 TI - Application of a Nonlinear Model to Transcript Levels of Upregulated Stress Response Gene ibpA in Stationary-Phase Salmonella enterica Subjected to Sublethal Heat Stress. AB - Sublethal heating, which can occur during slow cooking of meat products, is known to induce increased thermal resistance in Salmonella. However, very few studies have addressed the kinetics of this response. Although several recent studies have reported improved thermal inactivation models that include the effect of prior sublethal history on subsequent thermal resistance, none of these models were based on cellular-level responses to sublethal thermal stress. The goal of this study was to determine whether a nonlinear model could accurately portray the response of Salmonella to heat stress induced by prolonged exposure to sublethal temperatures. To accomplish this, stationary-phase Salmonella Montevideo cultures were subjected to various heating profiles (held at either 40 or 45 degrees C for 0, 5, 10, 15, 30, 60, 90, 180, or 240 min) using a PCR thermal cycler. Differential plating on selective and nonselective media was used to confirm the presence of cellular injury. Reverse transcription quantitative PCR was used to screen the transcript levels of six heat stress-related genes to find candidate genes for nonlinear modeling. Injury was detected in populations of Salmonella held at 45 degrees C for 30, 60, and 90 min and at 40 degrees C for 0, 5, and 90 min (P < 0.05), whereas no significant injury was found at 180 and 240 min (P > 0.05). The transcript levels of ibpA, which codes for a small heat shock protein associated with the ClpB and DnaK-DnaJ-GrpE chaperone systems, showed the greatest increase relative to the transcript levels at 0 min, which was significant at 5, 10, 15, 30, 60, 90, and 180 min at 45 degrees C and at 5, 10, 15, 30, 60, and 90 min at 40 degrees C (P < 0.05). Using ibpA transcript levels as an indicator of adaptation to thermal stress, a nonlinear model for sublethal injury is proposed. The use of variables indicating the physiological state of the pathogen during stress has the potential to increase the accuracy of thermal inactivation models that must account for prolonged exposure to sublethal temperatures. PMID- 27357028 TI - Cross-Laboratory Comparative Study of the Impact of Experimental and Regression Methodologies on Salmonella Thermal Inactivation Parameters in Ground Beef. AB - Isothermal inactivation studies are commonly used to quantify thermal inactivation kinetics of bacteria. Meta-analyses and comparisons utilizing results from multiple sources have revealed large variations in reported thermal resistance parameters for Salmonella, even when in similar food materials. Different laboratory or regression methodologies likely are the source of methodology-specific artifacts influencing the estimated parameters; however, such effects have not been quantified. The objective of this study was to evaluate the effects of laboratory and regression methodologies on thermal inactivation data generation, interpretation, modeling, and inherent error, based on data generated in two independent laboratories. The overall experimental design consisted of a cross-laboratory comparison using two independent laboratories (Michigan State University and U.S. Department of Agriculture, Agricultural Research Service, Eastern Regional Research Center [ERRC] laboratories), both conducting isothermal Salmonella inactivation studies (55, 60, 62 degrees C) in ground beef, and each using two methodologies reported in prior studies. Two primary models (log-linear and Weibull) with one secondary model (Bigelow) were fitted to the resultant data using three regression methodologies (two two-step regressions and a one-step regression). Results indicated that laboratory methodology impacted the estimated D60 degrees C- and z values (alpha = 0.05), with the ERRC methodology yielding parameter estimates ~25% larger than the Michigan State University methodology, regardless of the laboratory. Regression methodology also impacted the model and parameter error estimates. Two-step regressions yielded root mean square error values on average 40% larger than the one-step regressions. The Akaike Information Criterion indicated the Weibull as the more correct model in most cases; however, caution should be used to confirm model robustness in application to real-world data. Overall, the results suggested that laboratory and regression methodologies have a large influence on resultant data and the subsequent estimation of thermal resistance parameters. PMID- 27357029 TI - Salmonella and Escherichia coli O157:H7 Inactivation, Color, and Bioactive Compounds Enhancement on Raspberries during Frozen Storage after Decontamination Using New Formula Sanitizer Washing or Pulsed Light. AB - Berries are normally washed before they are frozen. Washing with sanitizer and treatment with pulsed light (PL) were studied for their effectiveness to inactivate foodborne pathogens on raspberries during frozen storage, while maintaining or enhancing major quality parameters. Raspberries were inoculated with Salmonella or Escherichia coli O157:H7 and then underwent a washing treatment with citric acid plus sodium dodecyl sulfate (CA+SDS) or citric acid plus thymol (CA+THY) or treatment with PL (dry PL, water-assisted [wet] PL, and PL-SDS). Pathogen survival was determined immediately after treatments and during frozen storage at -20 degrees C for 3 months. Washing with CA+SDS or CA+THY significantly reduced Salmonella (by 3.6 and 3.2 log CFU/g, respectively) and E. coli O157:H7 (by 4.1 and 3.7 log CFU/g, respectively). At the end of storage, washing with CA+SDS reduced Salmonella to 0.6 log CFU/g and E. coli O157:H7 to 0.5 log CFU/g; washing with CA+THY reduced Salmonella to 0.9 log CFU/g and E. coli O157:H7 to 0.5 log CFU/g. PL-SDS showed decontamination efficacy on raspberries, with 0.7 log CFU/g Salmonella and 0.9 log CFU/g E. coli O157:H7 surviving at the end of storage; in comparison, in the control, 1.6 log CFU/g Salmonella and 1.5 log CFU/g E. coli O157:H7 survived. Pathogen survival in raspberries that had been washed or treated with PL-SDS was significantly lower than in untreated raspberries. Major quality parameters, including color, total phenolic content, total anthocyanin content, total bacterial count, and total yeast and mold counts, were evaluated on raspberries immediately after treatments and during frozen storage. Redness increased in PL-treated raspberries. At the end of storage, PL-treated raspberries had significantly higher total phenolic content and total anthocyanin content compared with control samples. Washing with sanitizers and treatment with PL decreased the total bacterial count and total yeast and mold counts on raspberries and maintained the low counts. Our findings suggest that washing with a sanitizer or treatment with PL could be used to process frozen raspberries for enhanced food safety and quality. PMID- 27357031 TI - Biofilm Formation and Morphotypes of Salmonella enterica subsp.arizonae Differs from Those of Other Salmonella enterica Subspecies in Isolates from Poultry Houses. AB - Salmonella serovars are responsible for foodborne diseases around the world. The ability to form biofilms allows microorganisms to survive in the environment. In this study, 73 Salmonella strains, belonging to four different subspecies, were isolated from poultry houses and foodstuffs and tested. Biofilm formation was measured at four different temperatures and two nutrient concentrations. Morphotypes and cellulose production were evaluated at three different temperatures. The presence of several genes related to biofilm production was also examined. All strains and subspecies of Salmonella had the ability to form biofilms, and 46.57% of strains produced biofilms under all conditions tested. Biofilm formation was strain dependent and varied according to the conditions. This is the first study to analyze biofilm formation in a wide number of Salmonella enterica subsp. arizonae strains, and no direct relationship between the high prevalence of Salmonella enterica subsp. arizonae strains and their ability to form biofilm was established. Morphotypes and cellulose production varied as the temperature changed, with 20 degrees C being the optimum temperature for expression of the red, dry, and rough morphotype and cellulose. Salmonella enterica subsp. arizonae, whose morphotype is poorly studied, only showed a smooth and white morphotype and lacked the csgD and gcpA genes that are implicated in biofilm production. Thus, Salmonella biofilm formation under different environmental conditions is a public health problem because it can survive and advance through the food chain to reach the consumer. PMID- 27357030 TI - Inactivation of Salmonella on Sprouting Seeds Using a Spontaneous Carvacrol Nanoemulsion Acidified with Organic Acids. AB - Over the past decade, demand has increased for natural, minimally processed produce, including sprout-based products. Sanitization with 20,000 ppm of calcium hypochlorite is currently recommended for all sprouting seeds before germination to limit sprout-related foodborne outbreaks. A potentially promising disinfectant as an alternative to calcium hypochlorite is acidified spontaneous essential oil nanoemulsions. In this study, the efficacy of an acidified carvacrol nanoemulsion was tested against mung beans and broccoli seeds artificially contaminated with a Salmonella enterica Enteritidis cocktail (ATCC BAA-709, ATCC BAA-711, and ATCC BAA-1045). Treatments were performed by soaking inoculated seeds in acidified (50 mM acetic or levulinic acid) carvacrol nanoemulsions (4,000 or 8,000 ppm) for 30 or 60 min. After treatment, the number of surviving cells was determined via plate counts and/or the most probable number (MPN) approach. Treatment for 30 min successfully reduced Salmonella Enteritidis by 4 log CFU/g on mung beans (from an initial contamination level of 4.2 to 4.6 log CFU/g) and by 2 log CFU/g on broccoli seeds (from an initial contamination level of 2.4 to 2.6 log CFU/g) to below our detection limit (<=3 MPN/g). Treated seeds were sprouted and tested for the presence of pathogens and sprout yield. The final sprout product had no detectable pathogens, and total sprout yield was not influenced by any treatment. PMID- 27357032 TI - Assessing Transmission of Salmonella to Bovine Peripheral Lymph Nodes upon Horn Fly Feeding. AB - Biting arthropods are implicated in the transdermal transmission of Salmonella to bovine peripheral lymph nodes, and such contamination can contribute to increased Salmonella prevalence in processed beef. Since horn flies can acquire Salmonella and then excrete the bacteria in their feces, on-animal fly infestations were conducted in this study to assess whether horn flies have a role in this bacterial transmission. Three Salmonella serotypes were used to assess fly acquisition from and excretion onto cattle. The results indicated that flies can acquire Salmonella from the hide, as assessed by recovery from homogenates of surfacesterilized flies, and that Salmonella persists for at least 5 days in the fly. Fly fecal excreta serves as a bacterial contaminant on the hide, and the overall mean probable estimate of the quantity shed was ~10(5) most probable number per fly cage area. In 5 days, no transmission of the bacteria to bovine peripheral lymph nodes was evident, prompting an assessment of the effects of prolonged horn fly feeding on transmission. Three groups of animals were infested with flies that had consumed a blood meal containing Salmonella Senftenberg. After 5 days, the study was either terminated or the flies were removed and the cages replenished with unfed flies either once or twice over the course of an 11- or 19-day fly exposure period, respectively. A microlancet-inoculated positive control animal was included in each group for comparison. The impact of prolonged horn fly feeding was evident, as 8% of lymph nodes cultured were positive from the 5-day exposure, whereas 50 and 42% were positive from 11- and 19-day exposures, respectively. Higher concentrations of Salmonella were recovered from fly-infested animals than from the microlancet-inoculated control, likely a result of repeated inoculations over time by flies versus a single introduction. The data described provide new insights into the transmission dynamics of Salmonella in cattle populations, highlighting a role for biting flies as an important reservoir. PMID- 27357033 TI - Changes in Aerobic Plate and Escherichia coli-Coliform Counts and in Populations of Inoculated Foodborne Pathogens on Inshell Walnuts during Storage. AB - After harvest, inshell walnuts are dried using low-temperature forced air and are then stored in bins or silos for up to 1 year. To better understand the survival of bacteria on inshell walnuts, aerobic plate counts (APCs) and Escherichia coli?coliform counts (ECCs) were evaluated during commercial storage (10 to 12 degrees C and 63 to 65% relative humidity) over 9 months. APCs decreased by 1.4 to 2.0 log CFU per nut during the first 5 months of storage, and ECCs decreased by 1.3 to 2.2 log CFU per nut in the first month of storage. Through the remaining 4 to 8 months of storage, APCs and ECCs remained unchanged (P > 0.05) or decreased by <0.15 log CFU per nut per month. Similar trends were observed on kernels extracted from the inshell walnuts. APCs and ECCs were consistently and often significantly higher on kernels extracted from visibly broken inshell walnuts than on kernels extracted from visibly intact inshell walnuts. Parameters measured in this study were used to determine the survival of five-strain cocktails of E. coli O157:H7, Listeria monocytogenes, and Salmonella inoculated onto freshly hulled inshell walnuts (~8 log CFU/g) after simulated commercial drying (10 to 12 h; 40 degrees C) and simulated commercial storage (12 months at 10 degrees C and 65% relative humidity). Populations declined by 2.86, 5.01, and 4.40 log CFU per nut for Salmonella, E. coli O157:H7, and L. monocytogenes, respectively, after drying and during the first 8 days of storage. Salmonella populations changed at a rate of -0.33 log CFU per nut per month between days 8 and 360, to final levels of 2.83 +/- 0.79 log CFU per nut. E. coli and L. monocytogenes populations changed by -0.17 log CFU per nut per month and -0.26 log CFU per nut per month between days 8 and 360, respectively. For some samples, E. coli or L. monocytogenes populations were below the limit of detection by plating (0.60 log CFU per nut) by day 183 or 148, respectively; at least one of the six samples was positive at each subsequent sampling time by either plating or by enrichment. PMID- 27357034 TI - Vegetables and Restaurant Salads as a Reservoir for Shiga Toxigenic Escherichia coli: Distribution of Virulence Factors, O-Serogroups, and Antibiotic Resistance Properties. AB - Close contact of vegetables with soil, polluted water, and animal manure and unsanitary conditions during processing of restaurant salads led us to study the distribution of virulence factors, O-serogroups, and antibiotic resistance properties in Shiga toxigenic Escherichia coli (STEC) isolated from vegetables and salads. Samples of vegetables and salad (n = 420) were collected and evaluated for the presence of E. coli using culture and a PCR assay. Total prevalence of E. coli in studied samples was 49.5%. E. coli was found in 49.6% of vegetable samples and 49% of salad samples. Leek and traditional salad had the highest incidence of E. coli. Significant differences in the incidence of E. coli were found between the hot and cold seasons. Of the 149 E. coli isolates from vegetable samples, 130 (87%) were STEC, and of the 59 E. coli isolates from salad samples, 50 (84%) were STEC. The most commonly detected virulence factors were stx1 and eaeA. A significant difference was found between the frequency of the attaching and effacing and the enterohemorrhagic E. coli subtypes. Serogroups O26 (46% of isolates), O157 (14%), O121 (10%), and O128 (9%) were the most commonly detected serogroups among the STEC strains. The tetA, sul1, aac(3)-IV, dfrA1, blaSHV, and CITM antibiotic resistance genes were found in 96, 47.7, 90, 51, 27, and 93% of isolates, respectively. The highest levels of resistance were found against ampicillin (96.6% of isolates), tetracycline (87%), and gentamicin (90%). This study shows the importance of vegetables and salads as potential sources of E. coli infection. PMID- 27357035 TI - Epidemiological and Microbiological Investigation of an Outbreak of Severe Disease from Shiga Toxin-Producing Escherichia coli O157 Infection Associated with Consumption of a Slaw Garnish. AB - Investigating outbreaks of Shiga toxin-producing Escherichia coli (STEC) in England is a priority due to the potential severity of disease. However, there are often challenges in investigating outbreaks due to the small numbers of cases, poor patient recall, and low levels of bacteria that are challenging to detect in food samples using traditional laboratory culture techniques, and frequently a source is not identified. In September 2014, we investigated an STEC O157 outbreak associated with consuming a slaw garnish, and we report our findings here. Twenty confirmed cases were identified. Outbreak cases were interviewed, and menus reviewed to identify dishes consumed outside the home. Cases shared a history of eating meals at different chain restaurants. Analysis of menu items indicated shared consumption of slaw garnishes by 85.6% cases, although just 35.7% reported consuming them during interviews. Whole-genome sequencing linked cases where interpretation of the multilocus variable number tandem repeat analysis profile was obscured and indicated that the strain originated from a domestic (i.e., United Kingdom) source. Traceback identified that carrots and cabbages grown in the United Kingdom were the likely source of infection. Samples of products were examined, but STEC was not recovered. Epidemiological investigations linked the outbreak to consumption of a slaw garnish, which was poorly recalled by cases, and likely comprised of domestically produced raw vegetables. The causative organism was not isolated from food samples, and we conclude that future investigations should include sampling of animals and wildlife in the vicinity of farms where implicated produce is grown. PMID- 27357036 TI - Prevalence and Antibiotic Resistance Profiles of Extended-Spectrum beta-Lactamase Producing Escherichia coli Isolated from Healthy Broilers in Shandong Province, China. AB - Food-producing animals carrying extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) have posed a potential threat to human and animal health. However, information regarding ESBL-EC in the intensive broiler breeding areas of Shandong Province, People's Republic of China, is very limited. The goal of our study was to investigate the prevalence and drug resistance characteristics of ESBL-EC in healthy broilers from Shandong Province. A total of 142 ESBL-EC isolates were collected from four prefectures in Shandong Province from October 2014 to February 2015. ESBL-EC isolates were frequently detected (142 of 160 samples, 88.8%) in healthy broilers. Antibiotic susceptibility testing showed that all 142 ESBL-EC isolates were resistant to ampicillin, piperacillin, and cefazolin but were sensitive to imipenem and meropenem. All ESBL-EC isolates carried one or more of the bla genes, in which blaCTX-M, blaTEM 1, and blaSHV-5 genes were identified in 142, 106, and 5 isolates, respectively. The blaCTX-M gene includes blaCTX-M-15 (56), blaCTX-M-65 (42), blaCTX-M-55 (36), blaCTX-M-14 (21), blaCTX-M-79 (1), blaCTX-M-3 (1), blaCTX-M-123 (1), and blaCTX-M 132 (1). In addition, 17 ESBL-EC isolates cocarried the genes of the CTX-M-1 and CTX-M-9 groups. Our findings indicate that healthy broiler flocks in Shandong Province in China are an important reservoir for ESBL-EC, with blaCTX-M and blaTEM-1 being the prevalent resistance genes identified. PMID- 27357037 TI - Effect of Grapefruit Seed Extract on Thermal Inactivation of Listeria monocytogenes during Sous-Vide Processing of Two Marinated Mexican Meat Entrees. AB - D- and z-values for Listeria monocytogenes were obtained for two Mexican meat entrees: pork meat marinated in tomatillo (green tomato) sauce (PTS) and beef marinated in a red chili sauce (BRCS), with addition of 0, 200, and 800 ppm of grapefruit seed extract (GSE). Meat samples inoculated with L. monocytogenes were packaged in sterile bags, immersed in a water bath, and held at 55, 57.5, 60, and 62.5 degrees C for different periods of time. Depending upon the temperature, D values at 0 ppm of GSE ranged from 26.19 to 2.03 min in BRCS and 26.41 to 0.8 min in PTS. Adding 800 ppm of GSE to BRCS thermally treated at 55 and 62.5 degrees C significantly decreased inactivation time by 35%. A reduction in time of 25.9, 10.6, and 40.1% at 55, 57.5, and 60 degrees C, respectively, was observed in PTS with 800 ppm of GSE. The z-values of L. monocytogenes were not significantly affected by GSE addition; average z-values were 7.25 and 5.09 degrees C for BRCS and PTS, respectively. Estimated thermal lethality for a 7-D log reduction of L. monocytogenes under commercial-size sous-vide conditions at a reference temperature of 55 degrees C was reached at 78 and 71 min for BRCS without and with 800 ppm of GSE, respectively. For PTS, 7-D reduction was attained at 69 and 61 min without and with addition of 800 ppm of GSE, respectively. Supplementing both Mexican meat entrees (BRCS and PTS) with 800 ppm of GSE rendered L. monocytogenes cells more sensitive to the lethal effect of heat. The results of this study will assist the retail food industry in designing acceptance limits on critical control points pertaining to cooking regimes to effectively eliminate L. monocytogenes in BRCS and PTS sous-vide processed Mexican meat entrees. PMID- 27357038 TI - Quantifying the Risk of Human Toxoplasma gondii Infection Due to Consumption of Domestically Produced Lamb in the United States. AB - Toxoplasma gondii is a prevalent protozoan parasite worldwide. Human toxoplasmosis is responsible for considerable morbidity and mortality in the United States, and meat products have been identified as an important source of T. gondii infections in humans. The goal of this study was to develop a farm-to table quantitative microbial risk assessment model to predict the public health burden in the United States associated with consumption of U.S. domestically produced lamb. T. gondii prevalence in market lambs was pooled from the 2011 National Animal Health Monitoring System survey, and the concentration of the infectious life stage (bradyzoites) was calculated in the developed model. A log linear regression and an exponential doseresponse model were used to model the reduction of T. gondii during home cooking and to predict the probability of infection, respectively. The mean probability of infection per serving of lamb was estimated to be 1.5 cases per 100,000 servings, corresponding to ~6,300 new infections per year in the U.S. POPULATION: Based on the sensitivity analysis, we identified cooking as the most effective method to influence human health risk. This study provided a quantitative microbial risk assessment framework for T. gondii infection through consumption of lamb and quantified the infection risk and public health burden associated with lamb consumption. PMID- 27357039 TI - Assessment of Primary Production of Horticultural Safety Management Systems of Mushroom Farms in South Africa. AB - Growing global consumer concern over food safety in the fresh produce industry requires producers to implement necessary quality assurance systems. Varying effectiveness has been noted in how countries and food companies interpret and implement food safety standards. A diagnostic instrument (DI) for global fresh produce industries was developed to measure the compliancy of companies with implemented food safety standards. The DI is made up of indicators and descriptive grids for context factors and control and assurance activities to measure food safety output. The instrument can be used in primary production to assess food safety performance. This study applied the DI to measure food safety standard compliancy of mushroom farming in South Africa. Ten farms representing almost half of the industry farms and more than 80% of production were independently assessed for their horticultural safety management system (HSMS) compliance via in-depth interviews with each farm's quality assurance personnel. The data were processed using Microsoft Office Excel 2010 and are represented in frequency tables. The diagnosis revealed that the mushroom farming industry had an average food safety output. The farms were implementing an average-toadvanced HSMS and operating in a medium-risk context. Insufficient performance areas in HSMSs included inadequate hazard analysis and analysis of control points, low specificity of pesticide assessment, and inadequate control of suppliers and incoming materials. Recommendations to the industry and current shortcomings are suggested for realization of an improved industry-wide food safety assurance system. PMID- 27357040 TI - Microbial Indicator Profiling of Fresh Produce and Environmental Samples from Farms and Packing Facilities in Northern Mexico. AB - To compare microbiological indicator and pathogen contamination among different types of fresh produce and environmental samples along the production chain, 636 samples of produce (rinsates from cantaloupe melons, jalapeno peppers, and tomatoes) and environmental samples (rinsates from hands of workers, soil, and water) were collected at four successive steps in the production process (from the field before harvest through the packing facility) on 11 farms in northern Mexico during 2011 and 2012. Samples were assayed for enteric pathogens (Escherichia coli O157:H7, other Shiga toxigenic E. coli, Salmonella, and Listeria monocytogenes) and microbial indicators (coliforms, other E. coli strains, and Enterococcus spp.). Salmonella was the only pathogen detected; it was found in one preharvest jalapeno sample (detection limits: 0.0033 CFU/ml in produce and hand samples, 0.0013 CFU/ml in water, and 0.04 CFU/g in soil). Microbial indicator profiles for produce, worker hands, and soil from jalapeno and tomato farms were similar, but cantaloupe farm samples had higher indicator levels (P < 0.05 for all comparisons) on fruit (6.5, 2.8, and 7.2 log CFU per fruit) and hands (6.6, 3.1, and 7.1 log CFU per hand) for coliforms, E. coli, and Enterococcus, respectively, and lower E. coli levels in soil (<1 CFU/g). In water from tomato farms, E. coli indicators were significantly more prevalent (70 to 89% of samples were positive; P = 0.01 to 0.02), and geometric mean levels were higher (0.3 to 0.6 log CFU/100 ml) than those in cantaloupe farm water (32 to 38% of samples were positive, geometric mean <1 CFU/100 ml). Microbial indicators were present during all production steps, but prevalence and levels were generally highest at the final on-farm production step (the packing facility) (P < 0.03 for significant comparisons). The finding that microbial contamination on produce farms is influenced by produce type and production step can inform the design of effective approaches to mitigate microbial contamination. PMID- 27357041 TI - Food Safety Practices in the Egg Products Industry. AB - We conducted a national census survey of egg product plants (n = 57) to obtain information on the technological and food safety practices of the egg products industry and to assess changes in these practices from 2004 to 2014. The questionnaire asked about operational and sanitation practices, microbiological testing practices, food safety training for employees, other food safety issues, and plant characteristics. The findings suggest that improvements were made in the industry's use of food safety technologies and practices between 2004 and 2014. The percentage of plants using advanced pasteurization technology and an integrated, computerized processing system increased by almost 30 percentage points. Over 90% of plants voluntarily use a written hazard analysis and critical control point (HACCP) plan to address food safety for at least one production step. Further, 90% of plants have management employees who are trained in a written HACCP plan. Most plants (93%) conduct voluntary microbiological testing. The percentage of plants conducting this testing on egg products before pasteurization has increased by almost 30 percentage points since 2004. The survey findings identify strengths and weaknesses in egg product plants' food safety practices and can be used to guide regulatory policymaking and to conduct required regulatory impact analysis of potential regulations. PMID- 27357042 TI - Alternative Antimicrobial Commercial Egg Washing Procedures. AB - Commercial table eggs are washed prior to packaging. Standard wash procedures use an alkaline pH and warm water. If a cool water method could be developed that would still provide a microbiologically safe egg, the industry may save energy costs associated with water heating. Four wash procedures were evaluated for Salmonella reduction: pH 11 at 48.9 degrees C (industry standard), pH 11 at ambient temperature (~20 degrees C), pH 6 at 48.9 degrees C, and pH 6 at ambient temperature. Alkaline washes contained potassium hydroxide-based detergent, while pH 6 washes contained approximately 200 ppm of chlorine and a proprietary chlorine stabilizer (T-128). When eggs were inoculated by immersion in a cell suspension of Salmonella Enteritidis and Salmonella Typhimurium, all treatments resulted in a slight and similar reduction of Salmonella numbers (approximately 0.77 log CFU/ml of shell emulsion reduction). When eggs were inoculated by droplet on the shell surface, Salmonella counts were reduced by approximately 5 log CFU when washed with chlorine plus the chlorine stabilizer at both temperatures and with the alkaline wash at the high temperature. The reductions in Salmonella by these treatments were not significantly (P > 0.05) different from each other but were significantly (P < 0.05) more than the reduction observed for the 20 degrees C alkaline treatment and 20 degrees C control water treatments. Ambient temperature acidic washes reduced Salmonella contamination to the same degree as the standard pH 11 warm water wash and may be a viable option to reduce cost, increase shelf life, and slow pathogen growth in and on shell eggs. PMID- 27357043 TI - Food Consumption and Handling Survey for Quantitative Microbiological Consumer Phase Risk Assessments. AB - In the consumer phase of a typical quantitative microbiological risk assessment (QMRA), mathematical equations identify data gaps. To acquire useful data we designed a food consumption and food handling survey (2,226 respondents) for QMRA applications that is especially aimed at obtaining quantitative data. For a broad spectrum of food products, the survey covered the following topics: processing status at retail, consumer storage, preparation, and consumption. Questions were designed to facilitate distribution fitting. In the statistical analysis, special attention was given to the selection of the most adequate distribution to describe the data. Bootstrap procedures were used to describe uncertainty. The final result was a coherent quantitative consumer phase food survey and parameter estimates for food handling and consumption practices in The Netherlands, including variation over individuals and uncertainty estimates. PMID- 27357044 TI - Multidrug-Resistant Salmonella Isolates from Swine in the Eastern Cape Province, South Africa. AB - The exposure of farm animals to antimicrobials for treatment, prophylaxis, or growth promotion can select for resistant bacteria that can be transmitted to humans, and Salmonella as an important zoonotic pathogen can act as a potential reservoir of antimicrobial resistance determinants. We assessed the antibiogram profiles of Salmonella species isolated from pig herds in two commercial farms in South Africa. Two hundred fifty-eight presumptive Salmonella isolates were recovered from the fecal samples of 500 adult pigs. Specific primers targeting Salmonella serogroups A, B, C1, C2, and D were used to determine the prevalence of different serogroups. Only serogroup A (n = 48) was detected, while others were not. Antimicrobial susceptibility of the confirmed Salmonella serogroup A isolates was performed by using the disk diffusion method against a panel of 18 antibiotics. All the 48 isolates were resistant to tetracycline and oxytetracycline, while 75% were resistant to ampicillin, sulphamethoxazole trimethoprim, nalidixic acid, and streptomycin. All the isolates exhibited multidrug resistance, with the predominant phenotype being against 11 antibiotics, and multiple antibiotic resistance index ranged between 0.3 and 0.6. The incidence of genes encoding resistance against ampicillin (ampC), tetracycline (tetA), and streptomycin (strA) were 54, 61, and 44%, respectively. We conclude that healthy pigs are potential reservoirs of multidrug-resistant Salmonella that could be transmitted to humans through the food chain and, hence, a significant public health threat. PMID- 27357045 TI - Antimicrobial Resistance of Escherichia coli, Enterococci, Pseudomonas aeruginosa, and Staphylococcus aureus from Raw Fish and Seafood Imported into Switzerland. AB - A total of 44 samples of salmon, pangasius (shark catfish), shrimps, and oysters were tested for the presence of Escherichia coli, enterococci, Pseudomonas aeruginosa, and Staphylococcus aureus, which are indicator organisms commonly used in programs to monitor antibiotic resistance. The isolated bacterial strains, confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectroscopy, were tested against a panel of 29 antimicrobial agents to obtain MICs. Across the four sample types, Enterococcus faecalis (59%) was most common, followed by E. coli (55%), P. aeruginosa (27%), and S. aureus (9%). All bacterial species were resistant to some antibiotics. The highest rates of resistance were in E. faecalis to tetracycline (16%), in E. coli to ciprofloxacin (22%), and in S. aureus to penicillin (56%). Antibiotic resistance was found among all sample types, but salmon and oysters were less burdened than were shrimps and pangasius. Multidrug-resistant (MDR) strains were exclusively found in shrimps and pangasius: 17% of pangasius samples (MDR E. coli and S. aureus) and 64% of shrimps (MDR E. coli, E. faecalis, and S. aureus). Two of these MDR E. coli isolates from shrimps (one from an organic sample) were resistant to seven antimicrobial agents. Based on these findings, E. coli in pangasius, shrimps, and oysters, E. faecalis in pangasius, shrimps, and salmon, and P. aeruginosa in pangasius and shrimps are potential candidates for programs monitoring antimicrobial resistance. Enrichment methods for the detection of MDR bacteria of special public health concern, such as methicillin-resistant S. aureus and E. coli producing extended-spectrum beta-lactamases and carbapenemases, should be implemented. PMID- 27357046 TI - Higher Storage Temperature Causes Greater Salmonella enterica Serovar Typhimurium Internal Penetration of Artificially Contaminated, Commercially Available, Washed Free Range Eggs. AB - Foodborne salmonellosis is a major public health concern, with contaminated eggs identified as a significant source of infection. In Australia, the most prevalent cause of salmonellosis from eggs is Salmonella enterica subsp. enterica serovar Typhimurium. This study explored the effect of temperature after 1, 7, 14, 21, and 28 days of storage on commercially available washed free range eggs, artificially contaminated with Salmonella Typhimurium on the external surface. At each time point, the external surface of the egg, the crushed eggshell, and the internal egg yolk and albumen were analyzed for Salmonella. After 28 days of storage, 25% of eggs stored at 4 degrees C, 50% of eggs stored at 14 degrees C, and 100% of eggs stored at 23 and 35 degrees C were internally contaminated with Salmonella. After 1 day of storage, more than 50% of all eggs had Salmonella present in the crushed shell after the external surface had been disinfected with ethanol. This is the first study to demonstrate that refrigeration reduced the potential for Salmonella Typhimurium to penetrate the eggshell membrane and internally contaminate table eggs commercially available in Australia. It also suggests that the processes of cracking eggs may be a source of cross contamination within the kitchen. PMID- 27357047 TI - Transfer of Salmonella enterica Serovar Typhimurium from Beef to Tomato through Kitchen Equipment and the Efficacy of Intermediate Decontamination Procedures. AB - It is well established that a high percentage of foodborne illness is caused by failure of consumers to prepare food in a hygienic manner. Indeed, a common practice in households is to use the same kitchen equipment for both raw meat and fresh produce. Such a practice may lead to cross-contamination of fruits and vegetables, which are mainly consumed without further processing, with pathogenic microorganisms originating from raw meat. The present study was performed to examine the transfer of the pathogenic bacterium Salmonella enterica serovar Typhimurium from inoculated beef fillets to tomatoes via contact with high density polyethylene (PE), stainless steel (SS), and wooden (WD) surfaces and through cutting with SS knives. Furthermore, the following decontamination procedures were applied: (i) rinsing with tap water, (ii) scrubbing with tap water and liquid dish detergent, and (iii) using a commercial antibacterial spray. When surfaces and knives that came into contact with contaminated beef fillets were not cleaned prior to handling tomatoes, the lowest level of pathogen transfer to tomatoes was observed through PE surfaces. All of the decontamination procedures applied were more effective on knives than on surfaces, while among the surface materials tested, WD surfaces were the most difficult to decontaminate, followed by PE and SS surfaces. Mechanical cleaning with tap water and detergent was more efficient in decontaminating WD surfaces than using commercial disinfectant spray, followed by rinsing only with water. Specifically, reductions of 2.07 and 1.09 log CFU/cm(2) were achieved by washing the WD surfaces with water and detergent and spraying the surfaces with an antibacterial product, respectively. Although the pathogen's populations on SS and PE surfaces, as well as on tomatoes, after both aforementioned treatments were under the detection limit, the surfaces were all positive after enrichment, and thus, the potential risk of cross-contamination cannot be overlooked. As demonstrated by the results of this study, washing or disinfection of kitchen equipment may not be sufficient to avoid cross-contamination of ready-to-eat foods with foodborne pathogens, depending on the decontamination treatment applied and the material of the surfaces treated. Therefore, separate cutting boards and knives should be used for processing raw meat and preparing ready-to-eat foods in order to enhance food safety. PMID- 27357048 TI - Escherichia coli O157:H7 Cells Exposed to Lettuce Leaf Lysate in Refrigerated Conditions Exhibit Differential Expression of Selected Virulence and Adhesion Related Genes with Altered Mammalian Cell Adherence. AB - Contamination by and persistence of pathogenic bacteria in ready-to-eat produce have emerged as significant food safety and public health concerns. Viable produceborne pathogens cope with several stresses (e.g., temperature fluctuations and lowtemperature storage) during production and storage of the commodities. In this study, we investigated the impact of transient cold shock on Escherichia coli O157:H7 (EcO157) cells in a produce matrix (romaine lettuce leaf lysate). EcO157 cells were exposed to 25 degrees C for 1 h, 4 degrees C for 1 h, and 4 degrees C for 10 min in lettuce lysate. The expression of selected genes coding for virulence, stress response, and heat and cold shock proteins was quantified by real-time quantitative reverse transcription PCR assay. Treated EcO157 cells adhered to MAC-T mammalian cells were enumerated by in vitro bioassay. Expression of the Shiga toxin 1 gene (stx1a) was upregulated significantly (P < 0.05) upon cold shock treatments, but virulence genes related to EcO157 attachment (eaeA, lpfA, and hcpA) were down-regulated. Two key members of the cold shock regulon, cold shock protein (cspA) and gyrA, were significantly induced (P < 0.05) at the refrigeration temperature (4 degrees C). Significant upregulation of an SOS response gene, recA, was also observed. E. coli heat shock regulon member grpE was induced, but a universal stress protein (uspA) was downregulated at the refrigeration temperatures in lettuce lysate. The adhesion assay revealed a temperature-dependent reduction in the attachment of cold-shocked EcO157 cells. The results of the current study indicate a reduction in the attachment of cold shocked EcO157 to epithelial cells and higher levels of Shiga toxin gene expression at the molecular level. PMID- 27357049 TI - Enumeration of Escherichia coli O157:H7 in Outbreak-Associated Beef Patties. AB - An outbreak of five cases of Escherichia coli O157 infection that occurred in Canada in 2012 was linked to frozen beef patties seasoned with garlic and peppercorn. Unopened retail packs of beef patties from the implicated production lot were recovered and analyzed to enumerate E. coli O157, other E. coli strains, and total coliforms. E. coli O157 was not recovered by direct enumeration on selective agar media. E. coli O157 in the samples was estimated at 3.1 most probable number per 140 g of beef patty, other E. coli was 11 CFU/g, and coliforms were 120 CFU/g. These results indicate that the presence of E. coli O157 in ground beef at levels below 0.1 CFU/g may cause outbreaks. However, the roles of temperature abuse, undercooking, and crosscontamination in amplifying the risk are unknown. PMID- 27357050 TI - Survey of Deoxynivalenol and Aflatoxin B1 in Instant Noodles and Bread Consumed in Thailand by Using Liquid Chromatography-Tandem Mass Spectrometry. AB - One hundred wheat product samples (50 instant noodle samples and 50 bread samples) were collected from supermarkets in Bangkok, Thailand. Deoxynivalenol (DON) and aflatoxin B1 (AFB1) contamination in these products was analyzed using a validated liquid chromatography-tandem mass spectrometry method. The limit of quantification values of DON and AFB1 in the instant noodles and bread were 2 and 1 ng g(-1), respectively. The survey found that DON was quantifiable in 40% of collected samples, in 2% of noodles (0.089 MUg g(-1)), and in 78% of breads (0.004 to 0.331 MUg g(-1)). AFB1 was below the limit of quantification of the method in all of the tested samples. The results suggest that the risk of DON exposure via noodles and breads is very low in urban areas of Thailand. No risk can be attributable to AFB1 exposure in the same food matrices, but further studies with a larger sample size are needed to confirm these data. PMID- 27357051 TI - Persistence and Elimination of Human Norovirus in Food and on Food Contact Surfaces: A Critical Review. AB - This critical review addresses the persistence of human norovirus (NoV) in water, shellfish, and processed meats; on berries, herbs, vegetables, fruits, and salads; and on food contact surfaces. The review focuses on studies using NoV; information from studies involving only surrogates is not included. It also addresses NoV elimination or inactivation by various chemical, physical, or processing treatments. In most studies, persistence or elimination was determined by detection and quantification of the viral genome, although improved methods for determining infectivity have been proposed. NoV persisted for 60 to 728 days in water, depending on water source. It also persisted on berries, vegetables, and fruit, often showing <1-log reduction within 1 to 2 weeks. NoV was resilient on carpets, Formica, stainless steel, polyvinyl chloride, and ceramic surfaces; during shellfish depuration; and to repeated freeze-thaw cycles. Copper alloy surfaces may inactivate NoV by damaging viral capsids. Disinfection was achieved for some foods or food contact surfaces using chlorine, calcium or sodium hypochlorite, chlorine dioxide, high hydrostatic pressure, high temperatures, pH values >8.0, freeze-drying, and UV radiation. Ineffective disinfectants included hydrogen peroxide, quaternary ammonium compounds, most ethanol-based disinfectants, and antiseptics at normally used concentrations. Thorough washing of herbs and produce was effective in reducing, but not eliminating, NoV in most products. Washing hands with soap generally reduced NoV by <2 log. Recommendations for future research needs are provided. PMID- 27357052 TI - Childbirth after surgery for familial adenomatous polyposis in Japan. AB - PURPOSE: Familial adenomatous polyposis (FAP) is a genetic disorder. Some female patients with FAP can become pregnant. However, the current state of childbirth after surgery for FAP is unclear in Japan. METHODS: The study investigated 303 patients (147 female) who had undergone surgery for FAP at the 23 institutions between 2000 and 2012. RESULTS: Eighty female patients had information available on childbirth after surgery for FAP. Eight patients (10 %) gave birth after surgery. The mean age at surgery for FAP was 27 (range 20-41) years and 37 years in patients with and without childbirth after surgery, respectively (P = 0.044). The rate of childbirth after surgery was 17 % in women <=30 years of age and 13 % in those <=40 years of age. Although only one patient with invasive cancer (2.9 %) gave childbirth after surgery, seven patients without cancer (15.6 %) gave birth (P = 0.045). CONCLUSIONS: This study clarified the current state of childbirth after surgery for FAP in Japan. It is important to use these data to determine the best therapeutic approach for female FAP patients. PMID- 27357053 TI - The feasibility and safety of single-incision totally extraperitoneal inguinal hernia repair after previous lower abdominal surgery: 350 procedures at a single center. AB - PURPOSE: To evaluate the feasibility and safety of single-incision laparoscopic surgery for totally extraperitoneal inguinal hernia repair (SILS-TEP) with previous lower abdominal surgery (PLAS). METHODS: A retrospective analysis of 350 patients undergoing SILS-TEP for a primary inguinal hernia from January 2012 to December 2015 at Osaka Police Hospital was performed, and the outcomes of the patients with and without PLAS were compared. RESULTS: SILS-TEP was performed in 84 patients with PLAS and 266 patients without PLAS. Appendectomy was the most common previous operative procedure. There were more patients with an ASA score of >=3 in the PLAS group than in the control group (p < 0.05). The mean operative time, and the rates of conversion and postoperative complications were comparable between the two groups. There were no cases of recurrence in either group. CONCLUSIONS: SILS-TEP could be safely performed in patients with PLAS and achieved better cosmetic outcomes than conventional laparoscopic surgery. PMID- 27357054 TI - Dogfish glucagon analogues counter hyperglycaemia and enhance both insulin secretion and action in diet-induced obese diabetic mice. AB - AIMS: To investigate the antidiabetic actions of three dogfish glucagon peptide analogues [known glucagon-like peptide-1 and glucagon receptor co-agonists] after chronic administration in diet-induced high-fat-diet-fed diabetic mice. MATERIALS AND METHODS: National Institutes of Health Swiss mice were pre-conditioned to a high-fat diet (45% fat) for 100 days, and control mice were fed a normal diet (10% fat). Normal diet control and high-fat-fed control mice received twice-daily intraperitoneal (i.p.) saline injections, while the high-fat-fed treatment groups (n = 8) received twice-daily injections of exendin-4(1-39), [S2a]dogfish glucagon, [S2a]dogfish glucagon exendin-4(31-39) or [S2a]dogfish glucagon-Lys(30) -gamma-glutamyl-PAL (25 nmol/kg body weight) for 51 days. RESULTS: After dogfish glucagon analogue treatment, there was a rapid and sustained decrease in non fasting blood glucose and an associated insulinotropic effect (analysis of variance, p < .05 to <.001) compared with saline-treated high-fat-fed controls. All peptide treatments significantly improved i.p. and oral glucose tolerance with concomitant increased insulin secretion compared with saline-treated high fat-fed controls (p <.05 to <.001). After chronic treatment, no receptor desensitization was observed but insulin sensitivity was enhanced for all peptide treated groups (p < .01 to <.001) except [S2a]dogfish glucagon. Both exendin-4 and [S2a]dogfish glucagon exendin-4(31-39) significantly reduced plasma triglyceride concentrations compared with those found in lean controls (p = .0105 and p = .0048, respectively). Pancreatic insulin content was not affected by peptide treatments but [S2a]dogfish glucagon and [S2a]dogfish glucagon exendin 4(31-39) decreased pancreatic glucagon by 28%-34% (p = .0221 and p = .0075, respectively). The percentage of beta-cell area within islets was increased by exendin-4 and peptide analogue treatment groups compared with high-fat-fed controls and the beta-cell area decreased (p < .05 to <.01). CONCLUSIONS: Overall, dogfish glucagon co-agonist analogues had several beneficial metabolic effects, showing therapeutic potential for type 2 diabetes. PMID- 27357055 TI - Functional Photoacoustic Imaging of Gastric Acid Secretion Using pH-Responsive Polyaniline Nanoprobes. AB - A stomach functional imaging technique based on photoacoustics achieves noninvasive gastric acid secretory assessment utilizing pH-responsive polyaniline nanoprobes. A testing protocol mimicking clinical practice is established using a mouse model. After imaging, the nanoprobes are excreted outside the body without inducing systematic toxicity. Further optimization and translation of this technology can help alleviate patients' suffering and side effects. PMID- 27357056 TI - Detailed analysis of the supermarket task included on the Japanese version of the Rapid Dementia Screening Test. AB - AIM: The supermarket task, which is included in the Japanese version of the Rapid Dementia Screening Test, requires the quick (1 min) generation of words for things that can be bought in a supermarket. Cluster size and switches are investigated during this task. We investigated how the severity of dementia related to cluster size and switches on the supermarket task in patients with Alzheimer's disease. METHODS: We administered the Japanese version of the Rapid Dementia Screening Test to 250 patients with very mild to severe Alzheimer's disease and to 49 healthy volunteers. Patients had Mini-Mental State Examination scores from 12 to 26 and Clinical Dementia Rating scale scores from 0.5 to 3. Patients were divided into four groups based on their Clinical Dementia Rating score (0.5, 1, 2, 3). We performed statistical analyses between the four groups and control subjects based on cluster size and switch scores on the supermarket task. RESULTS: The score for cluster size and switches deteriorated according to the severity of dementia. Moreover, for subjects with a Clinical Dementia Rating score of 0.5, cluster size was impaired, but switches were intact. CONCLUSIONS: Our findings indicate that the scores for cluster size and switches on the supermarket task may be useful for detecting the severity of symptoms of dementia in patients with Alzheimer's disease. PMID- 27357057 TI - Salt intake and eating habits of school-aged children. AB - Salt restriction is important for the prevention and treatment of hypertension; however, salt consumption is still high in Japan. Improvements in dietary habits, including salt reduction in childhood, may contribute to the prevention of hypertension. The aim of the present study was to investigate the salt intake of school-aged children and the relationship between their diet diary and actual salt intake. The subjects comprised 580 schoolchildren (471 elementary school pupils and 109 junior high school pupils) who wanted to evaluate their salt intake in Kuji, a northeast coastal area in Japan. We estimated salt intake using spot urine samples and a formula. Lifestyle was assessed using a questionnaire. We also evaluated the salt intake and the lifestyles of 440 parents. The estimated salt intakes of elementary school pupils, junior high school pupils and their parents were 7.1+/-1.5, 7.6+/-1.5 and 8.0+/-1.7 g per day, respectively. The proportion of lower-grade children who achieved the recommended salt intake was low. In the multivariate analysis, the estimated salt intake of school-aged children correlated with their age, estimated salt intake of their parents and the menu priorities of the household. The estimated salt intake of the parents was associated with female gender, obesity, age and the habitual consumption of bread and noodles. In conclusion, the estimated salt intake of school-aged children positively correlated with the estimated salt intake of their parents, and the proportion of lower-grade children who achieved the recommended salt intake was low. Guidance on salt restriction for children and their parents may reduce the salt intake of school-aged children. PMID- 27357058 TI - Relations of body weight status in early adulthood and weight changes until middle age with hypertension in the Chinese population. AB - We conducted a retrospective cohort study of adult participants from the China Multicenter Collaborative Study of Cardiovascular Epidemiology to explore the relationship between early adulthood weight status, body weight change from age 25 to middle age and hypertension in the Chinese population. Self-reported weight was used to calculate the body mass index (BMI) at age 25. The association between BMI at age 25, subsequent weight change and hypertension was examined using a logistic regression model. Of the 14 635 study participants sampled in 1998, 3525 were diagnosed with hypertension. After adjusting for age, sex and other potential confounding factors, both the BMI at age 25 and weight gain were positively associated with the risk of hypertension (P for trend <0.001). Weight loss could more effectively reduce the risk of hypertension for participants with a higher BMI (BMI?24 kg m-2) at age 25 than for those who experienced a weight change of -2.5-2.5 kg. The odds ratio (OR) and 95% confidence interval (CI) for a weight change of -7.5 to -2.6 kg were 0.63 (0.46-0.86); for a weight change of < 7.5 kg, these statistics were 0.45 (0.32-0.63). For participants who had a lower BMI (18.5-20.9 kg m-2) at age 25, the OR and 95% CI were 0.86 (0.58-1.26) for a weight change of -7.5 to -2.6 kg and 0.95 (0.44-2.05) for a weight change of < 7.5 kg. Being overweight and obesity in early adulthood and adult weight gain were both independently associated with marked increase in the risk of hypertension in middle-aged men and women. Weight loss may be a protective factor against hypertension for people who were overweight or obese in early adulthood. PMID- 27357060 TI - Labeling the Stroma of a Patient-Derived Orthotopic Xenograft (PDOX) Mouse Model of Undifferentiated Pleomorphic Soft-Tissue Sarcoma With Red Fluorescent Protein for Rapid Non-Invasive Imaging for Drug Screening. AB - Our laboratory pioneered patient-derived orthotopic xenograft (PDOX) mouse models using surgical orthotopic implantation (SOI). PDOX models are patient-like, in contrast to the ectopic subcutaneous-transplant cancer models. In the present study, we demonstrate that an undifferentiated pleomorphic soft-tissue sarcoma (UPS-STS) PDOX model acquired bright RFP-expressing stroma through one passage in red fluorescent protein (RFP) transgenic mice, which upon passage to non-colored nude mice was non-invasively imageable. A PDOX nude mouse model of UPS-STS was established in the biceps femoris of nude mice. After the tumors grew to a diameter of 10 mm, the tumors were subsequently passaged to RFP transgenic mice, and after tumor growth were then passaged to non-transgenic nude mice. Tumors were divided into small fragments and transplanted in the biceps femoris at each passage. The OV100 Small Animal Fluorescence Imaging System and FV1000 laser scanning confocal microscope were used to image RFP fluorescence in the UPS-STS PDOX models. UPS-STS PDOX tumors, previously grown in RFP transgenic nude mice for only one passage, had very bright fluorescence and after passage to non transgenic nude mice maintained the bright fluorescence and were non-invasively imageable. FV1000 confocal imaging revealed diffusely distributed bright RFP stromal cells in the PDOX tumor, both in RFP transgenic mice and after passage to non-transgenic mice. These results demonstrate a powerful method to make the PDOX UPS-STS model brightly fluorescent for non-invasive imaging, as well as for confocal microscopy of individual stromal cells associated with the tumor. The RFP-labeled UPS PDOX has the potential to rapidly screen for novel effective agents for individual patients, including stroma-targeting drugs, whereby the stromal cells are a visual target. J. Cell. Biochem. 118: 361-365, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27357061 TI - The clinical and histopathological characteristics of early-onset basal cell carcinoma in Asians. AB - BACKGROUND: Basal cell carcinoma (BCC) is by far the most common cancer in white populations. In addition, recent reports have demonstrated an increasing incidence of BCC in Korea. We have observed a significant number of early-onset BCC cases in which the disease occurred in patients younger than 50 years. OBJECTIVE: To investigate the clinicopathological characteristics of early-onset BCC in an Asian population, specifically in Koreans. METHODS: One hundred and five patients with early-onset BCC were enrolled from a total of 1047 BCC patients who underwent surgery between January 1997 and December 2014 (942 patients over the age of 50 years were designated as the control group). RESULTS: Early-onset BCC accounted for 10.03% of all 1047 cases and the incidence over time displayed an incremental trend. The early-onset group displayed similar results as the control group, with a predominance of female BCC patients and the majority of tumours displaying the following characteristics: small in size, occurring in sun-exposed areas and belonging to the noduloulcerative clinical subtype and nodular histopathological subtype. In comparison with a previous study in a Western population, the incidence of the disease in non-exposed areas of the body, as well as the proportion of tumours of the superficial histological subtype, were lower in Asian patients. CONCLUSION: Although the clinicopathological characteristics of BCC are well-known, these characteristics have not been determined for early-onset BCC in an Asian population. Therefore, this study is the first report on early-onset BCC in Asians, specifically in a Korean patient group. PMID- 27357059 TI - Parasympathetic innervation of vertebrobasilar arteries: is this a potential clinical target? AB - This review aims to summarise the contemporary evidence for the presence and function of the parasympathetic innervation of the cerebral circulation with emphasis on the vertebral and basilar arteries (the posterior cerebral circulation). We consider whether the parasympathetic innervation of blood vessels could be used as a means to increase cerebral blood flow. This may have clinical implications for pathologies associated with cerebral hypoperfusion such as stroke, dementia and hypertension. Relative to the anterior cerebral circulation little is known of the origins and neurochemical phenotypes of the parasympathetic innervation of the vertebrobasilar arteries. These vessels normally provide blood flow to the brainstem and cerebellum but can, via the Circle of Willis upon stenosis of the internal carotid arteries, supply blood to the anterior cerebral circulation too. We review the multiple types of parasympathetic fibres and their distinct transmitter mechanisms and how these vary with age, disease and species. We highlight the importance of parasympathetic fibres for mediating the vasodilatory response to sympathetic activation. Current trials are investigating the possibility of electrically stimulating the postganglionic parasympathetic ganglia to improve cerebal blood flow to reduce the penumbra following stroke. We conclude that although there are substantial gaps in our understanding of the origins of parasympathetic innervation of the vertebrobasilar arteries, activation of this system under some conditions might bring therapeutic benefits. PMID- 27357064 TI - Evaluation of RNA and DNA extraction from liquid-based cytology specimens. AB - Molecular diagnosis using DNA and RNA derived from malignant tumors and molecular biological tools such as the quantitative polymerase-chain-reaction (qPCR) is a commonly used technique in clinical pathology. In this report, we compared the qualitative extraction of RNA and DNA from cancer cells fixed using several liquid-based cytology (LBC) kits. Ten to 1,000 cells from the T24 urinary bladder cancer cell line and SKG-II cervical cancer cell line were fixed with 55% methanol and three different methanol-based LBC solutions. The mRNA levels of CD44 in T24 cells and E7 in SKG-II cells and DNA levels of p53 in T24 cells and E7 in SKG-II cells were analyzed by qPCR. mRNA and DNA extracted from T24 and/or SKG-II cells fixed with methanol-based LBC solutions were efficiently detected, but to differing degrees, by qPCR. mRNA, and DNA from cells fixed with a formaldehyde-containing fixative liquid were detected at significantly low copy numbers by qPCR. Our results demonstrate that LBC systems are powerful tools for cytopathology and immunocytochemistry applications. However, the appropriate fixative must be selected for cell preservation when a small number of LBC samples is used for molecular testing, particularly in RNA-based molecular analyses. Diagn. Cytopathol. 2016;44:833-840. (c) 2016 Wiley Periodicals, Inc. PMID- 27357063 TI - Sphingosine 1-phosphate induced by hypoxia increases the expression of PAI-1 in HepG2 cells via HIF-1alpha. AB - Our group has recently reported that in the immortal human HepG2 liver cell line, sphingosine 1-phosphate (S1P) increases transcription of plasminogen activator inhibitor type-1 (PAI-1), the major physiological inhibitor of fibrinolysis, within 4 h. The present study aimed to elucidate the molecular mechanisms underlying this effect. PAI-1 expression was measured by reverse transcription quantitative polymerase chain reaction and immunoblotting. It was demonstrated that S1P increased PAI-1 promoter activity but did not increase the activity of promoters lacking the hypoxia responsive element (HRE) 2. In addition, S1P transiently increased the concentration of hypoxia inducible factor (HIF)-1alpha, a transcription factor capable of binding to HRE. When HIF-1alpha was knocked down, the induction of transcription of PAI-1 by S1P was no longer observed. Sphingosine kinase (SPHK) activity is increased by hypoxia. It was demonstrated that increases in the concentration of the HIF-1alpha protein induced by hypoxia were prevented by treatment with SPHK inhibitor or S1P receptor antagonists. Thus, modification of the induction of HIF-1alpha by S1P, leading to increased transcription of PAI-1, may be an attractive therapeutic target for thrombosis and consequent inhibition of fibrinolysis associated with hypoxia. PMID- 27357062 TI - Activation of Wnt Signaling by Mechanical Loading Is Impaired in the Bone of Old Mice. AB - Aging diminishes bone formation engendered by mechanical loads, but the mechanism for this impairment remains unclear. Because Wnt signaling is required for optimal loading-induced bone formation, we hypothesized that aging impairs the load-induced activation of Wnt signaling. We analyzed dynamic histomorphometry of 5-month-old, 12-month-old, and 22-month-old C57Bl/6JN mice subjected to multiple days of tibial compression and corroborated an age-related decline in the periosteal loading response on day 5. Similarly, 1 day of loading increased periosteal and endocortical bone formation in young-adult (5-month-old) mice, but old (22-month-old) mice were unresponsive. These findings corroborated mRNA expression of genes related to bone formation and the Wnt pathway in tibias after loading. Multiple bouts (3 to 5 days) of loading upregulated bone formation related genes, e.g., Osx and Col1a1, but older mice were significantly less responsive. Expression of Wnt negative regulators, Sost and Dkk1, was suppressed with a single day of loading in all mice, but suppression was sustained only in young-adult mice. Moreover, multiple days of loading repeatedly suppressed Sost and Dkk1 in young-adult, but not in old tibias. The age-dependent response to loading was further assessed by osteocyte staining for Sclerostin and LacZ in tibia of TOPGAL mice. After 1 day of loading, fewer osteocytes were Sclerostin positive and, corroboratively, more osteocytes were LacZ-positive (Wnt active) in both 5-month-old and 12-month-old mice. However, although these changes were sustained after multiple days of loading in 5-month-old mice, they were not sustained in 12-month-old mice. Last, Wnt1 and Wnt7b were the most load responsive of the 19 Wnt ligands. However, 4 hours after a single bout of loading, although their expression was upregulated threefold to 10-fold in young adult mice, it was not altered in old mice. In conclusion, the reduced bone formation response of aged mice to loading may be due to failure to sustain Wnt activity with repeated loading. (c) 2016 American Society for Bone and Mineral Research. PMID- 27357065 TI - High rate of A2142G point mutation associated with clarithromycin resistance among Iranian Helicobacter pylori clinical isolates. AB - This study aimed to investigate the clarithromycin resistance and its associated molecular mechanisms among Helicobacter pylori isolates from dyspeptic patients in Shiraz, Iran. From January to May 2014, 100 H. pylori strains were isolated from patients with gastroduodenal disorders. The resistance to clarithromycin was quantitatively evaluated, using Epsilometer (E-test) method. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed on all the isolates to detect A2143G and A2142G mutations in 23S rRNA gene. The H. pylori isolation rate was found to be 31.4%. E-test showed that 20% of isolates were resistant to clarithromycin (MIC >= 1 mg/L). MIC of clarithromycin ranged between 0.016 and 24 mg/L. Findings of PCR-RFLP showed that the A2142G was the most (90%) frequently point mutation, followed by the A2143G (10%). No statistically significant difference was found between H. pylori clarithromycin resistance point mutations and patients' gender or age. To the best of our knowledge, this is the first report of high frequency of A2142G point mutation in Iran and probably in other regions of the world. Considering the increasing trend of H. pylori resistance to clarithromycin due to these mutations, it is crucial to investigate the new therapeutic approaches against H. pylori infection. PMID- 27357066 TI - Diffusion Tensor Imaging to Map Brain Microstructural Changes in CADASIL. AB - BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) is sensitive to brain microstructural changes. The aims of this DTI study were to map voxelwise the spatial distribution of brain microstructural changes in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to investigate any correlation between DTI-derived indices and extension of T2 hyperintensity. METHODS: Eighteen patients with CADASIL and 18 age-, sex-, and education-level-matched healthy controls underwent magnetic resonance imaging at 3 T. Differences in DTI-derived indices (mean diffusivity [MD], fractional anisotropy [FA], axial [AD] and radial [RD] diffusivities, and mode of anisotropy [MO]) of brain white matter (WM) between CADASIL patients and healthy subjects were assessed through tract-based spatial statistics. Then, DTI derived indices were correlated with the patient's score on the extended Fazekas visual scale of the T2 hyperintensity. RESULTS: When compared to healthy controls, CADASIL patients showed extensive symmetric areas of increased MD/RD and decreased AD/FA/MO that involved almost the entire hemispheric cerebral WM (internal and external capsule, WM of the temporal poles, superior and inferior longitudinal fasciculus, inferior frontal-occipital fasciculus, uncinate fasciculus, cingulum, forceps major and minor, corticospinal tracts, and thalamic radiations), thalami, and corpus callosum. Additional areas of increased RD were observed in pons, midbrain, cerebellar peduncles, and cerebellar WM. Only FA was negatively correlated with extended Fazekas visual score. CONCLUSIONS: Our results indicate that brain damage in CADASIL is associated with extensive microstructural changes implying impairment of intra- and inter-hemispheric cerebral, thalamocortical, and cerebrocerebellar connections. Severity of microstructural changes correlates with extension of T2 hyperintensity. PMID- 27357067 TI - A resurrection experiment finds evidence of both reduced genetic diversity and potential adaptive evolution in the agricultural weed Ipomoea purpurea. AB - Despite the negative economic and ecological impact of weeds, relatively little is known about the evolutionary mechanisms that influence their persistence in agricultural fields. Here, we use a resurrection approach to examine the potential for genotypic and phenotypic evolution in Ipomoea purpurea, an agricultural weed that is resistant to glyphosate, the most widely used herbicide in current-day agriculture. We found striking reductions in allelic diversity between cohorts sampled nine years apart (2003 vs. 2012), suggesting that populations of this species sampled from agricultural fields have experienced genetic bottleneck events that have led to lower neutral genetic diversity. Heterozygosity excess tests indicate that these bottlenecks may have occurred prior to 2003. A greenhouse assay of individuals sampled from the field as seed found that populations of this species, on average, exhibited modest increases in herbicide resistance over time. However, populations differed significantly between sampling years for resistance: some populations maintained high resistance between the sampling years whereas others exhibited increased or decreased resistance. Our results show that populations of this noxious weed, capable of adapting to strong selection imparted by herbicide application, may lose genetic variation as a result of this or other environmental factors. We probably uncovered only modest increases in resistance on average between sampling cohorts due to a strong and previously identified fitness cost of resistance in this species, along with the potential that nonresistant migrants germinate from the seed bank. PMID- 27357068 TI - Simulated Bench Testing to Evaluate the Mechanical Performance of New Carotid Stents. AB - Our group recently developed a novel covered carotid stent that can prevent emboli while preserving the external carotid artery (ECA) branch blood flow. However, our recent in vitro side-branch ECA flow preservation tests on the covered stents revealed the need for further stent frame design improvements, including the consideration to crimp the stent to a low profile for the delivery of the stent system and having bigger cells. Hence, the current work aims to design new bare metal stents with bigger cell size to improve the crimpability and to accommodate more slits so that the side-branch flow could be further increased. Three new stent designs were analyzed using finite element analysis and benchmarked against two commercially available carotid stents in terms of their mechanical performances such as crimpability, radial strength, and flexibility. Results indicated that the new bare metal stent designs matched well against the commercial stents. Hence our new generation covered stents based on these designs can be expected to perform better in side-branch flow preservation without compromising on their mechanical performances. PMID- 27357069 TI - Olmutinib: First Global Approval. AB - Olmutinib (Olita(TM)) is an oral, third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that is being developed by Boehringer Ingelheim and Hanmi Pharmaceutical Co. Ltd for the treatment of non small cell lung cancer (NSCLC). Third-generation EGFR TKIs with covalent binding to the receptors demonstrate irreversible enzymatic inhibition of activating EGFR mutations and T790M mutation (a common reason for acquired EGFR TKI resistance), while sparing wild-type EGFR. In December 2015, olmutinib was granted breakthrough therapy designation in NSCLC by the US FDA. In May 2016, olmutinib received its first global approval in South Korea for the treatment of patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC. This article summarizes the milestones in the development of olmutinib leading to this first approval. PMID- 27357070 TI - Homolytic Cleavage of Both Heme-Bound Hydrogen Peroxide and Hydrogen Sulfide Leads to the Formation of Sulfheme. AB - Many heme-containing proteins with a histidine in the distal E7 (HisE7) position can form sulfheme in the presence of hydrogen sulfide (H2S) and a reactive oxygen species such as hydrogen peroxide. For reasons unknown, sulfheme derivatives are formed specifically on solvent-excluded heme pyrrole B. Sulfhemes severely decrease the oxygen-binding affinity in hemoglobin (Hb) and myoglobin (Mb). Here, use of hybrid quantum mechanical/molecular mechanical methods has permitted characterization of the entire process of sulfheme formation in the HisE7 mutant of hemoglobin I (HbI) from Lucina pectinata. This process includes a mechanism for H2S to enter the solvent-excluded active site through a hydrophobic channel to ultimately form a hydrogen bond with H2O2 bound to Fe(III). Proton transfer from H2O2 to His64 to form compound (Cpd) 0, followed by hydrogen transfer from H2S to the Fe(III)-H2O2 complex, results in homolytic cleavage of the O-O and S-H bonds to form a reactive thiyl radical (HS(*)), ferryl heme Cpd II, and a water molecule. Subsequently, the addition of HS(*) to Cpd II, followed by three proton transfer reactions, results in the formation of a three-membered ring ferric sulfheme that avoids migration of the radical to the protein matrix, in contrast to that in other peroxidative reactions. The transformation of this three membered episulfide ring structure to the five-membered thiochlorin ring structure occurs through a significant potential energy barrier, although both structures are nearly isoenergetic. Both three- and five-membered ring structures reveal longer NB-Fe(III) bonds compared with other pyrrole nitrogen-Fe(III) bonds, which would lead to decreased oxygen binding. Overall, these results are in agreement with a wide range of experimental data and provide fertile ground for further investigations of sulfheme formation in other heme proteins and additional effects of H2S on cell signaling and reactivity. PMID- 27357071 TI - [Update on the cutaneous neurobiology of pruritus]. AB - The pathogenesis of chronic and acute pruritus is not yet completely understood. Interactions of neurons with resident and nonresident skin cells seem to play an important role in the regulation of pruritus. Neuronal cells which express specific receptors and are capable of releasing neuromediators play an active role in this interaction. Furthermore, released neuromediators can activate immune cells including mast cells and eosinophils, which are increased in the inflammatory infiltrate of many pruritic skin diseases. Mast cells and eosinophils express receptors for neuromediators themselves. In addition, they can release neurotrophins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and cytokines including interleukin (IL)-31 which correlate with disease activity in patients with inflammatory skin diseases including atopic dermatitis and induce neuronal outgrowth. In part, a correlation of these mediators has also been described with pruritus. Although the interplay between transient and resident cells in the skin with peripheral nerves, mast cells, and eosinophils plays an important role in the mutual activation, the neurobiological mechanisms that lead to pruritus are not completely clear yet. PMID- 27357072 TI - Opportunities and challenges for implementing cost accounting systems in the Kenyan health system. AB - BACKGROUND: Low- and middle-income countries need to sustain efficiency and equity in health financing on their way to universal health care coverage. However, systems meant to generate quality economic information are often deficient in such settings. We assessed the feasibility of streamlining cost accounting systems within the Kenyan health sector to illustrate the pragmatic challenges and opportunities. DESIGN: We reviewed policy documents, and conducted field observations and semi-structured interviews with key informants in the health sector. We used an adapted Human, Organization and Technology fit (HOT fit) framework to analyze the components and standards of a cost accounting system. RESULTS: Among the opportunities for a viable cost accounting system, we identified a supportive broad policy environment, political will, presence of a national data reporting architecture, good implementation experience with electronic medical records systems, and the availability of patient clinical and resource use data. However, several practical issues need to be considered in the design of the system, including the lack of a framework to guide the costing process, the lack of long-term investment, the lack of appropriate incentives for ground-level staff, and a risk of overburdening the current health management information system. CONCLUSION: To facilitate the implementation of cost accounting into the health sector, the design of any proposed system needs to remain simple and attuned to the local context. PMID- 27357073 TI - Effect modification in the temperature extremes by mortality subgroups among the tropical cities of the Philippines. AB - BACKGROUND: Temperature-mortality relationships have been extensively probed with varying temperature range but with relatively similar patterns and in some instances are being modified by specific mortality groups such as causes of mortality, sex, and age. OBJECTIVE: This study aimed to determine the risk attributions in the extreme temperatures and also identified the risks associated with the various mortality subgroups. DESIGN: We used the 2006-2010 daily average meteorological and daily mortality variables from the Philippine Atmospheric Geophysical and Astronomical Services Administration and Philippine Statistics Authority-National Statistics Office, respectively. Mortality data were divided according to cause (cardiovascular and respiratory), sex, and age (0-14 years, 15 64 years, and >64 years). We performed a two-stage analysis to estimate the extreme temperature effects stratified by the different mortality subgroups to observe the effect modification. RESULTS: In the pooled analysis, greater risks were observed in the extreme high temperature (99th temperature percentile; RR (relative risk)=2.48 CI: 1.55-3.98) compared to the extreme low temperature (1st temperature percentile; RR=1.23 CI: 0.88-1.72). Furthermore, effect modification by mortality subgroups was evident, especially higher risks for extreme temperatures with respiratory-related diseases, women, and elderly. CONCLUSIONS: Both sex and age were found to effect modify the risks in extreme temperatures of tropical cities; hence, health-related policies should take these risk variations into consideration to create strategies with respect to the risk population. PMID- 27357074 TI - The START Study to evaluate the effectiveness of a combination intervention package to enhance antiretroviral therapy uptake and retention during TB treatment among TB/HIV patients in Lesotho: rationale and design of a mixed methods, cluster-randomized trial. AB - BACKGROUND: Initiating antiretroviral therapy (ART) early during tuberculosis (TB) treatment increases survival; however, implementation is suboptimal. Implementation science studies are needed to identify interventions to address this evidence-to-program gap. OBJECTIVE: The Start TB Patients on ART and Retain on Treatment (START) Study is a mixed-methods, cluster-randomized trial aimed at evaluating the effectiveness, cost-effectiveness, and acceptability of a combination intervention package (CIP) to improve early ART initiation, retention, and TB treatment success among TB/HIV patients in Berea District, Lesotho. DESIGN: Twelve health facilities were randomized to receive the CIP or standard of care after stratification by facility type (hospital or health center). The CIP includes nurse training and mentorship, using a clinical algorithm; transport reimbursement and health education by village health workers (VHW) for patients and treatment supporters; and adherence support using text messaging and VHW. Routine data were abstracted for all newly registered TB/HIV patients; anticipated sample size was 1,200 individuals. A measurement cohort of TB/HIV patients initiating ART was recruited; the target enrollment was 384 individuals, each to be followed for the duration of TB treatment (6-9 months). Inclusion criteria were HIV-infected; on TB treatment; initiated ART within 2 months of TB treatment initiation; age >=18; English- or Sesotho-speaking; and capable of informed consent. The exclusion criterion was multidrug-resistant TB. Three groups of key informants were recruited from intervention clinics: early ART initiators; non/late ART initiators; and health care workers. Primary outcomes include ART initiation, retention, and TB treatment success. Secondary outcomes include time to ART initiation, adherence, change in CD4+ count, sputum smear conversion, cost-effectiveness, and acceptability. Follow-up and data abstraction are complete. DISCUSSION: The START Study evaluates a CIP targeting barriers to early ART implementation among TB/HIV patients. If the CIP is found effective and acceptable, this study has the potential to inform care for TB/HIV patients in high-burden, resource-limited countries in sub-Saharan Africa. PMID- 27357075 TI - Modeling solutions to Tanzania's physician workforce challenge. AB - BACKGROUND: There is a great need for physicians in Tanzania. In 2012, there were approximately 0.31 physicians per 10,000 individuals nationwide, with a lower ratio in the rural areas, where the majority of the population resides. In response, universities across Tanzania have greatly increased the enrollment of medical students. Yet evidence suggests high attrition of medical graduates to other professions and emigration from rural areas where they are most needed. OBJECTIVE: To estimate the future number of physicians practicing in Tanzania and the potential impact of interventions to improve retention, we built a model that tracks medical students from enrollment through clinical practice, from 1990 to 2025. DESIGN: We designed a Markov process with 92 potential states capturing the movement of 25,000 medical students and physicians from medical training through employment. Work possibilities included clinical practice (divided into rural or urban, public or private), non-clinical work, and emigration. We populated and calibrated the model using a national 2005/2006 physician mapping survey, as well as graduation records, graduate tracking surveys, and other available data. RESULTS: The model projects massive losses to clinical practice between 2016 and 2025, especially in rural areas. Approximately 56% of all medical school students enrolled between 2011 and 2020 will not be practicing medicine in Tanzania in 2025. Even with these losses, the model forecasts an increase in the physician-to population ratio to 1.4 per 10,000 by 2025. Increasing the absorption of recent graduates into the public sector and/or developing a rural training track would ameliorate physician attrition in the most underserved areas. CONCLUSIONS: Tanzania is making significant investments in the training of physicians. Without linking these doctors to employment and ensuring their retention, the majority of this investment in medical education will be jeopardized. PMID- 27357076 TI - Nickel-Catalyzed Reductive Amidation of Unactivated Alkyl Bromides. AB - A user-friendly, nickel-catalyzed reductive amidation of unactivated primary, secondary, and tertiary alkyl bromides with isocyanates is described. This catalytic strategy offers an efficient synthesis of a wide range of aliphatic amides under mild conditions and with an excellent chemoselectivity profile while avoiding the use of stoichiometric and sensitive organometallic reagents. PMID- 27357077 TI - Always on my mind: Headache in children. PMID- 27357078 TI - An improved spreadsheet for calculating limb length discrepancy and epiphysiodesis timing using the multiplier method. AB - PURPOSE: The multiplier method is a technique to predict limb length discrepancy (LLD) at maturity in pediatric patients. Various tools have been developed for performing the multiplier calculations to predict LLD and timing of epiphysiodesis. These include multiplier/growth applications (apps) and a spreadsheet which have helped to facilitate LLC calculations in an efficient and easy manner. We have updated the spreadsheet to improve features for making LLD calculations and facilitate pasting data into electronic medical records (EMRs). METHODS: Tools currently in use were critically examined for features that limited their function, created possible sources of error or could be more user friendly. These features were modified and recreated in an improved Excel spreadsheet that uses patient age, sex, limb lengths, and previous lengthening surgeries as inputs to predict LLD at maturity and offer options for timing of epiphysiodesis for both congenital and developmental LLD. Our multiplier spreadsheet function was then compared to manual calculations and other multiplier tools for accuracy and ease of use. RESULTS: Our spreadsheet accurately calculates LLD at maturity and timing of epiphysiodesis when compared to other methods. It contains a function to calculate predicted leg lengths after previous lengthenings, and concise single-page worksheets for developmental LLD, congenital LLD, and height prediction. CONCLUSIONS: This spreadsheet was developed to provide a more efficient and user-friendly method of calculating LLD at maturity and timing of epiphysiodesis. It can easily be pasted into the EMR for ease of documentation. We recommend this method for both clinical practice and educational use. PMID- 27357079 TI - Novel insights from quantitative imaging of the developing cerebellum. AB - There is increasing evidence that points to the central role of the cerebellum in many areas of human behaviour - in health and in illness. The findings reviewed here shed further light on the developmental vulnerability of cerebellar cell types, and highlight the new imaging techniques being used in this research. This article reviews some new advances in our understanding of the normal cerebellar growth trajectory, and how this may become disturbed by pathological processes. Cerebellar development is now being implicated in many conditions, from autism and other neuropsychiatric disorders to diabetes. PMID- 27357080 TI - Functional Diversity as a New Framework for Understanding the Ecology of an Emerging Generalist Pathogen. AB - Emerging infectious disease outbreaks are increasingly suspected to be a consequence of human pressures exerted on natural ecosystems. Previously, host taxonomic communities have been used as indicators of infectious disease emergence, and the loss of their diversity has been implicated as a driver of increased presence. The mechanistic details in how such pathogen-host systems function, however, may not always be explained by taxonomic variation or loss. Here we used machine learning and methods based on Gower's dissimilarity to quantify metrics of invertebrate functional diversity, in addition to functional groups and their taxonomic diversity at sites endemic and non-endemic for the model generalist pathogen Mycobacterium ulcerans, the causative agent of Buruli ulcer. Changes in these metrics allowed the rapid categorisation of the ecological niche of the mycobacterium's hosts and the ability to relate specific host traits to its presence in aquatic ecosystems. We found that taxonomic diversity of hosts and overall functional diversity loss and evenness had no bearing on the mycobacterium's presence, or whether the site was in an endemic area. These findings, however, provide strong evidence that generalist environmentally persistent bacteria such as M. ulcerans can be associated with specific functional traits rather than taxonomic groups of organisms, increasing our understanding of emerging disease ecology and origin. PMID- 27357081 TI - Ecosystem Services Connect Environmental Change to Human Health Outcomes. PMID- 27357082 TI - Methylmercury and Total Mercury in Eels, Anguilla anguilla, from Lakes in Northeastern Poland: Health Risk Assessment. AB - In the aquatic environment, mercury is readily methylated into its most toxic form of methylmercury. In this form, it enters the aquatic food chain and its concentrations increase in subsequent links, which decreases the quality of fish meat and poses risks to consumer health. Concentrations of methylmercury (MeHg) and total mercury (THg) were determined in the muscle tissues of 64 eel specimens measuring from 59 to 95 cm in length as functions of specimen size and weight. Risks posed to consumers by eel from different length classes were also assessed. The mean concentration of THg in all of the eel examined was 0.179 mg kg-1, but the range was from 0.028 to 0.487 mg kg-1. The mean concentration of MeHg was 0.147 mg kg-1, and the range was also wide from 0.023 to 0.454 mg kg-1. Accumulated MeHg and THg increased with eel body length. The percentage share of MeHg in THg also changed with specimen length, and there was a positive correlation between the concentrations of MeHg and THg. Risk assessment was performed based on the doses of THg and MeHg ingested with fish for several specimen length classes. Consuming the meat of eel measuring 80 cm in length increased the estimated weekly intake (EWI) of THg and MeHg twofold in comparison to that from specimens 60 cm in length and fourfold in specimens exceeding 90 cm in length. The percentage shares of the EWI in the tolerable weekly intake and the target hazard quotient coefficient also increased proportionally. Generally, concentrations of MeHg and THg in eel are below current limits and pose no risk to consumer health as long as the consumption of larger specimens is avoided. PMID- 27357085 TI - Enhancing antitumor activity of silver nanoparticles by modification with cell penetrating peptides. AB - Recently, silver nanoparticles (AgNPs) have been used for cancer treatment. To achieve a successful anticancer activity, AgNP needs to be delivered sufficiently to the cells. Cell-penetrating peptides (CPPs) are small cationic peptides that have ability to transport various cargos across cell membranes. In this study, a strategy was developed for cancer treatment, where AgNP modified with CPPs displayed dramatically antitumor activity in MCF-7 cell lines. Peptides-modified AgNPs showed significant enhancement in killing tumor cells by increasing the uptake of AgNP into cell lines and could be a new class of nano-drug for cancer treatment. PMID- 27357084 TI - Long Term Complications in Pediatric Liver Transplant Recipients: What Every Pediatrician Should Know. AB - The outcomes of liver transplantation in the pediatric population have improved significantly over the past two decades. As long-term survival improves, potential complications related to immunosuppression, delayed growth and development, and metabolic issues have started to be seen more commonly in long term survivors. Hence, general pediatricians should to be aware of these potential complications in order to optimize the medical care and the quality of life for children with liver transplantation. PMID- 27357086 TI - Histopathological Findings in Brains of Patients Who Died in the Acute Stage of Poor-grade Subarachnoid Hemorrhage. AB - Patients with poor-grade aneurysmal subarachnoid hemorrhage (SAH) are likely to die due to irreversible acute-stage primary brain damage. However, the mechanism(s) and pathology responsible for their high mortality rate remain unclear. We report our findings on the brains of individuals who died in the acute stage of SAH. An autopsy was performed on the brains of 11 SAH patients (World Federation of Neurosurgical Societies grade 5) who died within 3 days of admission and who did not receive respiratory assistance. All brains were free of intracranial hematoma and hydrocephalus; all harbored ruptured aneurysms. In all brains, multiple infarcts with perifocal edema were scattered throughout the cortex and subcortical white matter of the whole brain. Infarcts with a patchy - were more often seen than infarcts with a wedge-shaped pattern. Microscopic examination revealed multiple areas with cytotoxic edema and neuronal death indicative of acute ischemic changes. Edema and congestion were more obvious in areas where the subarachnoid clot tightly adhered to the pia mater. Pathologically, the brains of deceased patients with acute poor-grade SAH were characterized by edema and multifocal infarcts spread throughout the whole brain; they were thought to be attributable to venous ischemia. Diffuse disturbance in venous drainage attributable to an abrupt increase in the intracranial pressure and focal disturbances due to tight adhesion of the subarachnoid clot to the pia mater, may contribute strongly to irreversible brain damage in the acute stage of SAH. PMID- 27357083 TI - CMP-N-acetylneuraminic acid synthetase interacts with fragile X related protein 1. AB - Fragile X mental retardation protein (FMRP), fragile X related 1 protein (FXR1P) and FXR2P are the members of the FMR protein family. These proteins contain two KH domains and a RGG box, which are characteristic of RNA binding proteins. The absence of FMRP, causes fragile X syndrome (FXS), the leading cause of hereditary mental retardation. FXR1P is expressed throughout the body and important for normal muscle development, and its absence causes cardiac abnormality. To investigate the functions of FXR1P, a screen was performed to identify FXR1P interacting proteins and determine the biological effect of the interaction. The current study identified CMP-N-acetylneuraminic acid synthetase (CMAS) as an interacting protein using the yeast two-hybrid system, and the interaction between FXR1P and CMAS was validated in yeast using a beta-galactosidase assay and growth studies with selective media. Furthermore, co-immunoprecipitation was used to analyze the FXR1P/CMAS association and immunofluorescence microscopy was performed to detect expression and intracellular localization of the proteins. The results of the current study indicated that FXR1P and CMAS interact, and colocalize in the cytoplasm and the nucleus of HEK293T and HeLa cells. Accordingly, a fragile X related 1 (FXR1) gene overexpression vector was constructed to investigate the effect of FXR1 overexpression on the level of monosialotetrahexosylganglioside 1 (GM1). The results of the current study suggested that FXR1P is a tissue-specific regulator of GM1 levels in SH-SY5Y cells, but not in HEK293T cells. Taken together, the results initially indicate that FXR1P interacts with CMAS, and that FXR1P may enhance the activation of sialic acid via interaction with CMAS, and increase GM1 levels to affect the development of the nervous system, thus providing evidence for further research into the pathogenesis of FXS. PMID- 27357087 TI - Results From 10 Years of Interprofessional Training on Motivational Interviewing. AB - Motivational interviewing (MI) is a popular evidence-based method to support health behavior change. We examined evaluations from 10 years of interprofessional workshops on MI to identify trends in trainees' MI-related knowledge, attitude, and behavior. From 2006 to 2015, 394 trainees participated in continuing education MI workshops with our team and completed a validated posttraining questionnaire. Participants were 90% female and 66% White, with M = 12 years in practice. They worked in pediatric and adult care; urban and rural locations; and inpatient, outpatient, and nonhealth settings. The largest groups were nurses (20%), allied health professionals (20%), and health educators or case managers (15%). Trainees' professional diversity increased over time, their average age and years in practice decreased, and the percentage with prior MI training increased. Practitioners in telehealth and nonhealth settings had lower scores overall. Outcomes varied significantly by professional discipline: Mental health professionals, case managers, health educators, and nurses had higher scores on some outcome variables than nonhealth professionals. Years of clinical experience predicted MI-consistent attitude, but prior training, other demographic variables, and training process variations had no consistent effects. Although many trainees had already received MI training, outcome measures showed room for improvement. MI presents continued opportunities for interprofessional education. PMID- 27357088 TI - Mirror Mirror on the Wall, Which Is the Most Convincing of Them All? Exploring Anti-Domestic Violence Posters. AB - Although domestic abuse of women by men has received significant media, police, and research attention, domestic violence directed toward men has been marginalized across the board and is still rarely treated seriously. The purpose of this research, then, is to examine and compare different anti-domestic violence messages in which the abuser's gender is not always clear. In Study 1, 200 U.K. participants (100 females and 100 males, aged 18-67, M = 28.98, SD = 9.613) evaluated posters that varied across three levels; in that the subject (male or female) was depicted as being silenced, bruised, or experiencing live abuse. The results showed that the posters featuring female victims were all rated as more effective than posters showing male victims. In Study 2, 140 different U.K. participants (95 females; 45 males) aged 18 to 59 (M = 27.27, SD = 10.662) evaluated the cartoon facial images of Disney characters who had been altered to look like victims of violence and real-life corresponding photos of human models. The results showed that the realistic posters were found to be more believable, emotional, and effective than the cartoons. The implications of such perceptions are discussed. PMID- 27357090 TI - Spot urine sodium measurements do not accurately estimate dietary sodium intake in chronic kidney disease. AB - BACKGROUND: Sodium intake influences blood pressure and proteinuria, yet the impact on long-term outcomes is uncertain in chronic kidney disease (CKD). Accurate assessment is essential for clinical and public policy recommendations, but few large-scale studies use 24-h urine collections. Recent studies that used spot urine sodium and associated estimating equations suggest that they may provide a suitable alternative, but their accuracy in patients with CKD is unknown. OBJECTIVE: We compared the accuracy of 4 equations [the Nerbass, INTERSALT (International Cooperative Study on Salt, Other Factors, and Blood Pressure), Tanaka, and Kawasaki equations] that use spot urine sodium to estimate 24-h sodium excretion in patients with moderate to advanced CKD. DESIGN: We evaluated the accuracy of spot urine sodium to predict mean 24-h urine sodium excretion over 9 mo in 129 participants with stage 3-4 CKD. Spot morning urine sodium was used in 4 estimating equations. Bias, precision, and accuracy were assessed and compared across each equation. RESULTS: The mean age of the participants was 67 y, 52% were female, and the mean estimated glomerular filtration rate was 31 +/- 9 mL . min(-1) . 1.73 m(-2) The mean +/- SD number of 24-h urine collections was 3.5 +/- 0.8/participant, and the mean 24-h sodium excretion was 168.2 +/- 67.5 mmol/d. Although the Tanaka equation demonstrated the least bias (mean: -8.2 mmol/d), all 4 equations had poor precision and accuracy. The INTERSALT equation demonstrated the highest accuracy but derived an estimate only within 30% of mean measured sodium excretion in only 57% of observations. Bland-Altman plots revealed systematic bias with the Nerbass, INTERSALT, and Tanaka equations, underestimating sodium excretion when intake was high. CONCLUSION: These findings do not support the use of spot urine specimens to estimate dietary sodium intake in patients with CKD and research studies enriched with patients with CKD. The parent data for this study come from a clinical trial that was registered at clinicaltrials.gov as NCT00785629. PMID- 27357091 TI - Schooling and wage income losses due to early-childhood growth faltering in developing countries: national, regional, and global estimates. AB - BACKGROUND: The growth of >300 million children <5 y old was mildly, moderately, or severely stunted worldwide in 2010. However, national estimates of the human capital and financial losses due to growth faltering in early childhood are not available. OBJECTIVE: We quantified the economic cost of growth faltering in developing countries. DESIGN: We combined the most recent country-level estimates of linear growth delays from the Nutrition Impact Model Study with estimates of returns to education in developing countries to estimate the impact of early-life growth faltering on educational attainment and future incomes. Primary outcomes were total years of educational attainment lost as well as the net present value of future wage earnings lost per child and birth cohort due to growth faltering in 137 developing countries. Bootstrapped standard errors were computed to account for uncertainty in modeling inputs. RESULTS: Our estimates suggest that early-life growth faltering in developing countries caused a total loss of 69.4 million y of educational attainment (95% CI: 41.7 million, 92.6 million y) per birth cohort. Educational attainment losses were largest in South Asia (27.6 million y; 95% CI: 20.0 million, 35.8 million y) as well as in Eastern (10.3 million y; 95% CI: 7.2 million, 12.9 million y) and Western sub-Saharan Africa (8.8 million y; 95% CI: 6.4 million, 11.5 million y). Globally, growth faltering in developing countries caused a total economic cost of $176.8 billion (95% CI: $100.9 billion, $262.6 billion)/birth cohort at nominal exchange rates, and $616.5 billion (95% CI: $365.3 billion, $898.9 billion) at purchasing power parity-adjusted exchange rates. At the regional level, economic costs were largest in South Asia ($46.6 billion; 95% CI: $33.3 billion, $61.1 billion), followed by Latin America ($44.7 billion; 95% CI: $19.2 billion, $74.6 billion) and sub-Saharan Africa ($34.2 billion; 95% CI: $24.4 billion, $45.3 billion). CONCLUSIONS: Our results indicate that the annual cost of early-childhood growth faltering is substantial. Further investment in scaling up effective interventions in this area is urgently needed and likely to yield long run benefits of $3 for every $1 invested. PMID- 27357089 TI - Prediagnostic selenium status and hepatobiliary cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort. AB - BACKGROUND: Selenium status is suboptimal in many Europeans and may be a risk factor for the development of various cancers, including those of the liver and biliary tract. OBJECTIVE: We wished to examine whether selenium status in advance of cancer onset is associated with hepatobiliary cancers in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. DESIGN: We assessed prediagnostic selenium status by measuring serum concentrations of selenium and selenoprotein P (SePP; the major circulating selenium transfer protein) and examined the association with hepatocellular carcinoma (HCC; n = 121), gallbladder and biliary tract cancers (GBTCs; n = 100), and intrahepatic bile duct cancer (IHBC; n = 40) risk in a nested case-control design within the EPIC study. Selenium was measured by total reflection X-ray fluorescence, and SePP was determined by a colorimetric sandwich ELISA. Multivariable ORs and 95% CIs were calculated by using conditional logistic regression. RESULTS: HCC and GBTC cases, but not IHBC cases, showed significantly lower circulating selenium and SePP concentrations than their matched controls. Higher circulating selenium was associated with a significantly lower HCC risk (OR per 20-MUg/L increase: 0.41; 95% CI: 0.23, 0.72) but not with the risk of GBTC or IHBC. Similarly, higher SePP concentrations were associated with lowered HCC risk only in both the categorical and continuous analyses (HCC: P-trend <= 0.0001; OR per 1.5-mg/L increase: 0.37; 95% CI: 0.21, 0.63). CONCLUSION: These findings from a large prospective cohort provide evidence that suboptimal selenium status in Europeans may be associated with an appreciably increased risk of HCC development. PMID- 27357092 TI - Vitamin D status is associated with uteroplacental dysfunction indicated by pre eclampsia and small-for-gestational-age birth in a large prospective pregnancy cohort in Ireland with low vitamin D status. AB - BACKGROUND: Associations between vitamin D and pregnancy outcomes have been inconsistent. OBJECTIVES: We described the distribution of 25-hydroxyvitamin D3 [25(OH)D3], 3-epi-25(OH)D3, and 25(OH)D2 in early pregnancy and investigated associations with pre-eclampsia and small-for-gestational-age (SGA) birth, which are indicative of uteroplacental dysfunction. DESIGN: The SCOPE (Screening for Pregnancy Endpoints) Ireland prospective pregnancy cohort study included 1768 well-characterized low-risk, nulliparous women resident at 52 degrees N. Serum 25(OH)D3, 3-epi-25(OH)D3, and 25(OH)D2 were quantified at 15 wk of gestation with the use of a CDC-accredited liquid chromatography-tandem mass spectrometry method. RESULTS: The mean +/- SD total 25(OH)D concentration was 56.7 +/- 25.9 nmol/L, and 17% and 44% of women had 25(OH)D concentrations <30 and <50 nmol/L, respectively. The prevalence of pre-eclampsia was 3.8%, and 10.7% of infants were SGA. There was a lower risk of pre-eclampsia plus SGA combined (13.6%) at 25(OH)D concentrations >75 nmol/L (adjusted OR: 0.64; 95% CI: 0.43, 0.96). The main predictors of 25(OH)D were the use of vitamin D-containing supplements (adjusted mean difference: 20.1 nmol/L; 95% CI: 18.5, 22.7 nmol/L) and summer sampling (adjusted mean difference: 15.5 nmol/L; 95% CI: 13.4, 17.6 nmol/L). Non-Caucasian ethnicity (adjusted mean difference: -19.3 nmol/L; 95% CI: -25.4, -13.2 nmol/L) and smoking (adjusted mean difference: -7.0 nmol/L; 95% CI: -10.5, -3.6 nmol/L) were negative predictors of 25(OH)D. The mean +/- SD concentration of 3-epi 25(OH)D3, which was detectable in 99.9% of samples, was 2.6 +/- 1.6 nmol/L. Determinants of 3-epi-25(OH)D3 were 25(OH)D3 (adjusted mean difference: 0.052 nmol/L; 95% CI: 0.050, 0.053 nmol/L) and maternal age (adjusted mean difference: 0.018 nmol/L; 95% CI: -0.026, -0.009 nmol/L). The mean +/- SD concentration of 25(OH)D2 was 3.1 +/- 2.7 nmol/L, which was present in all samples. No adverse effects of 25(OH)D concentrations >125 nmol/L were observed. CONCLUSIONS: In the first report to our knowledge of CDC-accredited 25(OH)D data and pregnancy outcomes from a large, clinically validated, prospective cohort study, we observed a protective association of a 25(OH)D concentration >75 nmol/L and a reduced risk of uteroplacental dysfunction as indicated by a composite outcome of SGA and pre-eclampsia. Well-designed, adequately powered randomized controlled trials are required to verify this observation. The SCOPE pregnancy cohort was registered at www.anzctr.org.au as ACTRN12607000551493. PMID- 27357093 TI - No differential effect of beverages sweetened with fructose, high-fructose corn syrup, or glucose on systemic or adipose tissue inflammation in normal-weight to obese adults: a randomized controlled trial. AB - BACKGROUND: Sugar-sweetened beverage (SSB) consumption and low-grade chronic inflammation are both independently associated with type 2 diabetes and cardiovascular disease. Fructose, a major component of SSBs, may acutely trigger inflammation, which may be one link between SSB consumption and cardiometabolic disease. OBJECTIVE: We sought to determine whether beverages sweetened with fructose, high-fructose corn syrup (HFCS), and glucose differentially influence systemic inflammation [fasting plasma C-reactive protein and interleukin-6 (IL-6) as primary endpoints] acutely and before major changes in body weight. Secondary endpoints included adipose tissue inflammation, intestinal permeability, and plasma fetuin-A as potential mechanistic links between fructose intake and low grade inflammation. DESIGN: We conducted a randomized, controlled, double-blind, crossover design dietary intervention (the Diet and Systemic Inflammation Study) in 24 normal-weight to obese adults without fructose malabsorption. Participants drank 4 servings/d of fructose-, glucose-, or HFCS-sweetened beverages accounting for 25% of estimated calorie requirements while consuming a standardized diet ad libitum for three 8-d periods. RESULTS: Subjects consumed 116% of their estimated calorie requirement while drinking the beverages with no difference in total energy intake or body weight between groups as reported previously. Fasting plasma concentrations of C-reactive protein and IL-6 did not differ significantly at the end of the 3 diet periods. We did not detect a consistent differential effect of the diets on measures of adipose tissue inflammation except for adiponectin gene expression in adipose tissue (P = 0.005), which was lowest after the glucose phase. We also did not detect consistent evidence of a differential impact of these sugars on measures of intestinal permeability (lactulose:mannitol test, plasma zonulin, and plasma lipopolysaccharide-binding protein). CONCLUSION: Excessive amounts of fructose, HFCS, and glucose from SSBs consumed over 8 d did not differentially affect low-grade chronic systemic inflammation in normal weight to obese adults. This trial was registered at clinicaltrials.gov as NCT01424306. PMID- 27357095 TI - Zinc carnosine works with bovine colostrum in truncating heavy exercise-induced increase in gut permeability in healthy volunteers. AB - BACKGROUND: Heavy exercise causes gut symptoms and, in extreme cases, heat stroke that is due to the increased intestinal permeability of luminal toxins. OBJECTIVE: We examined whether zinc carnosine (ZnC), a health-food product taken alone or in combination with bovine colostrum (a natural source of growth factors), would moderate such effects. DESIGN: Eight volunteers completed a 4 arm, double-blind, placebo-controlled crossover protocol (14 d of placebo, ZnC, colostrum, or ZnC plus colostrum) before undertaking standardized exercise 2 and 14 d after the start of treatment. Changes in epithelial resistance, apoptosis signaling molecules, and tight junction (TJ) protein phosphorylation in response to a 2 degrees C rise in body temperature were determined with the use of Caco-2 and HT29 intestinal cells. RESULTS: Body temperature increased 2 degrees C, and gut permeability (5-h urinary lactulose:rhamnose ratios) increased 3-fold after exercise (from 0.32 +/- 0.016 baseline to 1.0 +/- 0.017 at 14 d; P < 0.01). ZnC or colostrum truncated the rise by 70% after 14 d of treatment. The combination treatment gave an additional benefit, and truncated exercise induced increase at 2 d (30% reduction; P < 0.01). A 2 degrees C temperature rise in in vitro studies caused the doubling of apoptosis and reduced epithelial resistance 3-4-fold. ZnC or colostrum truncated these effects (35-50%) with the greatest response seen with the combination treatment (all P < 0.01). Mechanisms of action included increasing heat shock protein 70 and truncating temperature-induced changes in B cell leukemia/lymphoma-2 associated X protein alpha and B cell lymphoma 2. ZnC also increased total occludin and reduced phosphorylated tyrosine claudin, phosphorylated tyrosine occludin, and phosphorylated serine occludin, thereby enhancing the TJ formation and stabilization. CONCLUSION: ZnC, taken alone or with colostrum, increased epithelial resistance and the TJ structure and may have value for athletes and in the prevention of heat stroke in military personnel. This trial was registered at www.isrctn.com as ISRCTN51159138. PMID- 27357094 TI - Effect of an Internet-based, personalized nutrition randomized trial on dietary changes associated with the Mediterranean diet: the Food4Me Study. AB - BACKGROUND: Little is known about the efficacy of personalized nutrition (PN) interventions for improving consumption of a Mediterranean diet (MedDiet). OBJECTIVE: The objective was to evaluate the effect of a PN intervention on dietary changes associated with the MedDiet. DESIGN: Participants (n = 1607) were recruited into a 6-mo, Internet-based, PN randomized controlled trial (Food4Me) designed to evaluate the effect of PN on dietary change. Participants were randomly assigned to receive conventional dietary advice [control; level 0 (L0)] or PN advice on the basis of current diet [level 1 (L1)], diet and phenotype [level 2 (L2)], or diet, phenotype, and genotype [level 3 (L3)]. Dietary intakes from food-frequency questionnaires at baseline and at 6 mo were converted to a MedDiet score. Linear regression compared participant characteristics between high (>5) and low (<=5) MedDiet scores. Differences in MedDiet scores between treatment arms at month 6 were evaluated by using contrast analyses. RESULTS: At baseline, high MedDiet scorers had a 0.5 lower body mass index (in kg/m(2); P = 0.007) and a 0.03 higher physical activity level (P = 0.003) than did low scorers. MedDiet scores at month 6 were greater in individuals randomly assigned to receive PN (L1, L2, and L3) than in controls (PN compared with controls: 5.20 +/- 0.05 and 5.48 +/- 0.07, respectively; P = 0.002). There was no significant difference in MedDiet scores at month 6 between PN advice on the basis of L1 compared with L2 and L3. However, differences in MedDiet scores at month 6 were greater in L3 than in L2 (L3 compared with L2: 5.63 +/- 0.10 and 5.38 +/- 0.10, respectively; P = 0.029). CONCLUSIONS: Higher MedDiet scores at baseline were associated with healthier lifestyles and lower adiposity. After the intervention, MedDiet scores were greater in individuals randomly assigned to receive PN than in controls, with the addition of DNA-based dietary advice resulting in the largest differences in MedDiet scores. Although differences were significant, their clinical relevance is modest. This trial was registered at clinicaltrials.gov as NCT01530139. PMID- 27357096 TI - Inhibition of Carbonyl Reductase 1 Safely Improves the Efficacy of Doxorubicin in Breast Cancer Treatment. AB - AIMS: Doxorubicin (DOX) is a chemotherapeutic drug that is used to treat many cancers, but its use is limited by cardiotoxic side effect. Carbonyl reductase 1 (CBR1) is an NADPH-dependent oxidoreductase that reduces DOX to doxorubicinol (DOXOL), a less potent derivative that is responsible for DOX cardiotoxicity. Thus, we aimed to demonstrate that inhibition of CBR1 enhances the chemotherapeutic efficacy of DOX and attenuates cardiotoxicity. RESULTS: Pharmacological or genetic inhibition of CBR1 improved the anticancer effects of DOX in preclinical models of breast cancer. RNA interference or chemical inhibition of CBR1 improved the anticancer effect of DOX in breast cancer. Moreover, CBR1 overexpression enabled breast cancer cells to obtain chemotherapeutic resistance to DOX treatment. Intriguingly, inhibition of CBR1 decreased DOX-induced cardiotoxicity in animal model. Innovation and Conclusions: Inhibition of CBR1 increases chemotherapeutic efficacy of DOX and reduces cardiotoxicity by blocking DOX reduction to DOXOL. Therefore, we offer preclinical proof-of-concept for a combination strategy to safely leverage the efficacy of doxorubicin by blunting its cardiotoxic effects that limit use of this cytotoxic agent used widely in the oncology clinic. Antioxid. Redox Signal. 26, 70-83. PMID- 27357097 TI - Rhodium(i)-catalysed skeletal reorganisation of benzofused spiro[3.3]heptanes via consecutive carbon-carbon bond cleavage. AB - Skeletal reorganisation of benzofused spiro[3.3]heptanes has been achieved using rhodium(i) catalysts. The reaction of benzofused 2-(2 pyridylmethylene)spiro[3.3]heptanes proceeds via sequential C-C bond oxidative addition and beta-carbon elimination. On the other hand, benzofused spiro[3.3]heptan-2-ols undergo two consecutive beta-carbon elimination processes. In both cases, substituted naphthalenes are obtained. PMID- 27357098 TI - Outcomes of a community-based weight management programme for morbidly obese populations. AB - BACKGROUND: Morbid obesity is an ongoing concern worldwide. There is a paucity of research reporting primary care outcomes focussed on complex and morbidly obese populations. The National Institute for Health and Care Excellence (NICE) recommends a specialist, multidisciplinary weight management team for the successful management of such populations. This is the first service evaluation reporting both primary (weight change) and secondary [body mass index (BMI), waist circumference, physical activity levels, fruit and vegetable intake, Rosenberg self-esteem score] outcomes in these patients. METHODS: The present study comprised a prospective observational study of a cohort data set for patients (n = 288) attending their 3-month and 6-month (n = 115) assessment appointments at a specialist community weight management programme. RESULTS: Patients had a mean (SD) initial BMI of 45.5 (6.6) kg m- 2; 66% were females. Over 80% of patients attending the service lost some weight by 3 months. Average absolute weight loss was 4.11 (4.95) kg at 3 months and 6.30 (8.41) kg at 6 months, equating to 3.28% (3.82%) and 4.90% (6.26%), respectively, demonstrating a statistically significant weight change at both time points (P < 0.001). This meets NICE best practice guidelines for the commissioning of services leading to a minimum of 3% average weight loss, with at least 30% of patients losing at >=5% of their initial weight. Waist measurement and BMI were reduced significantly at 3 months. Improvements were also seen in physical activity levels, fruit and vegetable consumption, and self-esteem levels (P < 0.001). CONCLUSIONS: This service was successful in aiding weight loss in morbidly obese populations. The findings of the present study support the view that weight-loss targets of 3% are realistic. PMID- 27357099 TI - Waiting Time Intervals for Non-small Cell Lung Cancer Diagnosis and Treatment in Alberta: Quantification of Intervals and Identification of Risk Factors Associated with Delays. AB - AIMS: Very little is known regarding the time required to diagnose and treat patients with non-small cell lung cancer (NSCLC) in Canada. We sought to quantify diagnostic and treatment intervals for NSCLC care in Alberta and identify risk factors for delays. MATERIALS AND METHODS: The Alberta Cancer Registry identified all cases of stage I-III NSCLC diagnosed and treated in Alberta, Canada from 2004 to 2011. Diagnostic data were obtained from physician billing, inpatient/outpatient hospital data and electronic medical records to quantify the duration of diagnostic and treatment intervals and their sum (system interval). Multivariable logistic regression was carried out to identify factors associated with delays. RESULTS: Of the 3009 eligible patients included, the median and 90th percentile system interval was 78 (95% confidence interval 76-80) and 185 days (95% confidence interval 178-195), respectively. The treatment interval was longer than the diagnostic interval, with medians of 51 (95% confidence interval 49-53) and 38 (95% confidence interval 36-40) days, respectively. After adjustment, age > 60 years and treatment by modalities other than supportive care (especially surgery) were associated with delays. Factors associated with prompt care included high acuity presentations and stage III disease. CONCLUSION: The majority of Albertans with potentially curable NSCLC exceeded guidelines for the timeliness of their care. PMID- 27357100 TI - Deregulated microRNA expression and its pathogenetic implications for myelodysplastic syndromes. AB - OBJECTIVE: Myelodysplastic syndromes (MDS) include a heterogeneous group of clonal hematological stem cell disorders characterized by ineffective hematopoiesis, cytopenias. MicroRNAs (miRNAs) are short non-coding RNA molecules that repress gene expression at the post-transcriptional level. In this review, we summarize advanced investigations that underscore deregulated miRNA expression in MDS, and discuss the implications of miRNAs in the molecular pathogenesis of MDS. METHODS: Relevant English-language literatures were searched and retrieved from PubMed using the terms MDS and miRNAs. RESULTS: The majority of studies have focused on profiling miRNA expression in MDS, only a small number of studies have investigated the exact pathogenic role of miRNAs in MDS. DISCUSSION: In the hematopoietic system, miRNAs are critical regulators of the differentiation of hematopoietic stem/progenitor cells. Thus, it is not surprising that dysregulation of miRNAs can lead to hematopoietic stem cell anomalies and further cause MDS. Deregulated miRNA expression has been identified in MDS, and it contributes to the pathogenesis and progression of MDS. Chromosomal aberrations, hypermethylation of miRNA promoters, and mutations of miRNA genes may lead to dysregulation of miRNA in MDS. However, the complex regulatory networks between miRNAs and their potential target genes in MDS still need to be explored in further studies. CONCLUSIONS: Although the function of miRNAs is not fully understood, these small non-coding RNAs represent novel pathogenetic and clinical implications in MDS. The studies of miRNAs may guide us towards a better understanding of this disease and shed light on the development of new therapeutic strategies. PMID- 27357101 TI - Identification of a positive-Seebeck-coefficient exohedral fullerene. AB - If fullerene-based thermoelectricity is to become a viable technology, then fullerenes exhibiting both positive and negative Seebeck coefficients are needed. C60 is known to have a negative Seebeck coefficient and therefore in this paper we address the challenge of identifying a positive-Seebeck-coefficient fullerene. We investigated the thermoelectric properties of single-molecule junctions of the exohedral fullerene C50Cl10 connected to gold electrodes and found that it indeed possesses a positive Seebeck coefficient. Furthermore, in common with C60, the Seebeck coefficient can be increased by placing more than one C50Cl10 in series. For a single C50Cl10, we find S = +8 MUV K(-1) and for two C50Cl10's in series we find S = +30 MUV K(-1). We also find that the C50Cl10 monomer and dimer have power factors of 0.5 * 10(-5) W m(-1) K(-2) and 6.0 * 10(-5) W m(-1) K(-2) respectively. These results demonstrate that exohedral fullerenes provide a new class of thermoelectric materials with desirable properties, which complement those of all-carbon fullerenes, thereby enabling the boosting of the thermovoltage in all-fullerene tandem structures. PMID- 27357103 TI - Prevention of urinary tract infections with vitamin D supplementation 20,000 IU per week for five years. Results from an RCT including 511 subjects. AB - BACKGROUND: In observational studies vitamin D deficiency is associated with increased risk of infections, whereas the effect of vitamin D supplementation in randomized controlled trials is non-conclusive. METHODS: Five hundred and eleven subjects with prediabetes were randomized to vitamin D3 (20,000 IU per week) versus placebo for five years. Every sixth month, a questionnaire on respiratory tract infections (RTI) (common cold, bronchitis, influenza) and urinary tract infection (UTI) was filled in. RESULTS: Mean baseline serum 25-hydroxyvitamin D (25(OH)D) level was 60 nmol/L. Two hundred and fifty-six subjects received vitamin D and 255 placebo. One hundred and sixteen subjects in the vitamin D and 111 in the placebo group completed the five-year study. Eighteen subjects in the vitamin D group and 34 subjects in the placebo group reported UTI during the study (p < 0.02), whereas no significant differences were seen for RTI. The effect on UTI was most pronounced in males. The effect of vitamin D on UTI was unrelated to baseline serum 25(OH)D level. CONCLUSION: Supplementation with vitamin D might prevent UTI, but confirmatory studies are needed. PMID- 27357104 TI - Enhanced piezoelectricity in (1 -x)Bi1.05Fe1-yAyO3-xBaTiO3 lead-free ceramics: site engineering and wide phase boundary region. AB - Site engineering has been employed to modulate the piezoelectric activity of high temperature (1 -x)Bi1.05Fe1-yScyO3-xBaTiO3 lead-free ceramics fabricated by a conventional solid-state method together with a quenching technique. The effects of x and y content on the phase structure, microstructure, and electrical properties have been investigated in detail. A wide rhombohedral (R) to pseudo cubic (C) phase boundary was formed in the ceramics with x = 0.30 and 0 <=y<= 0.07, thus leading to enhanced piezoelectricity (d33 = 120-180 pC N(-1)), ferroelectricity (Pr = 19-22 MUC cm(-2)) and a high Curie temperature (TC = 478 520 degrees C). In addition, the influence of different element substitutions for Fe(3+) on phase structure and electrical behavior was also investigated. Improved piezoelectricity (d33 = 160-180 pC N(-1)) and saturated P-E loops can be simultaneously achieved in the ceramics with A = Sc, Ga, and Al due to the R-C phase boundary. As a result, site engineering may be an efficient way to modulate the piezoelectricity of BiFeO3-BaTiO3 lead-free ceramics. PMID- 27357105 TI - Retrospective Cohort Study Comparing Redo Operations Using Ferromagnetic Dissection and Conventional Monopolar Dissection. AB - Purpose To evaluate effectiveness of a novel hemostatic dissection tool in patients with congenital heart disease undergoing redo pericardiac dissections. Description This dissection tool employs ferromagnetic energy to cut and coagulate. The unit passes no electric current through the patient, thus eliminating cautery-induced dysrhythmias and electrical interference. Ferromagnetic dissection is precise and reduces thermal injury spread by as much as 90%. Evaluation We case matched 22 patients undergoing reoperation for congenital heart surgery by weight/operation. Group 1 used the ferromagnetic tool, and Group 2 used conventional monopolar cautery for pericardiac dissection. For groups 1 and 2, the mean weight was 27.7 and 28.4, respectively (P = .87). Time (minutes) from skin incision to cardiopulmonary bypass was 71 versus 72 (P = .44), cardiopulmonary bypass (minutes) was 75.6 versus 73.6 (P = .42), total operative time (minutes) was 193 versus 201 (P = .34). Chest tube output/kilogram in first 6 and first 24 hours was 0.4 versus 1.3 (P = .02) and 0.8 versus 2.4 (P = .01) for groups 1 and 2, respectively. Re-exploration for bleeding was 0% versus 9% (P = .07). There was no mortality. Conclusion The ferromagnetic dissection system appears safe and efficacious. Bleeding was significantly decreased and the need for re-exploration reduced. PMID- 27357106 TI - Dynamics of internally functionalized dendrimers. AB - The internally functionalized dendrimers are novel polymers that differ from conventional dendrimers by having additional functional units which do not branch out further. We investigate the dynamics of these structures with the inclusion of local semiflexibility and analyze their eigenmodes. The functionalized units clearly manifest themselves leading to a group of eigenvalues which are not present for homogeneous dendrimers. This part of the spectrum reveals itself in the local relaxation, leading to a corresponding process in the imaginary part of the complex dielectric susceptibility. PMID- 27357102 TI - omega-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies. AB - IMPORTANCE: The role of omega-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE: To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5omega-3), docosapentaenoic acid (DPA; 22:5omega-3), and docosahexaenoic acid (DHA; 22:6omega-3) and plant-derived alpha-linolenic acid (ALA; 18:3omega-3) for incident CHD. DATA SOURCES: A global consortium of 19 studies identified by November 2014. STUDY SELECTION: Available prospective (cohort, nested case control) or retrospective studies with circulating or tissue omega-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS: Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, omega-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES: Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS: The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with omega-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the omega-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85 0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE: On the basis of available studies of free living populations globally, biomarker concentrations of seafood and plant derived omega-3 fatty acids are associated with a modestly lower incidence of fatal CHD. PMID- 27357107 TI - A structured overview of trends and technologies used in dynamic hand orthoses. AB - The development of dynamic hand orthoses is a fast-growing field of research and has resulted in many different devices. A large and diverse solution space is formed by the various mechatronic components which are used in these devices. They are the result of making complex design choices within the constraints imposed by the application, the environment and the patient's individual needs. Several review studies exist that cover the details of specific disciplines which play a part in the developmental cycle. However, a general collection of all endeavors around the world and a structured overview of the solution space which integrates these disciplines is missing. In this study, a total of 165 individual dynamic hand orthoses were collected and their mechatronic components were categorized into a framework with a signal, energy and mechanical domain. Its hierarchical structure allows it to reach out towards the different disciplines while connecting them with common properties. Additionally, available arguments behind design choices were collected and related to the trends in the solution space. As a result, a comprehensive overview of the used mechatronic components in dynamic hand orthoses is presented. PMID- 27357108 TI - Assessment of clinically related outcomes and biomarker analysis for translational integration in colorectal cancer (ACROBATICC): study protocol for a population-based, consecutive cohort of surgically treated colorectal cancers and resected colorectal liver metastasis. AB - BACKGROUND: More accurate predictive and prognostic biomarkers for patients with colorectal cancer (CRC) primaries or colorectal liver metastasis (CLM) are needed. Outside clinical trials, the translational integration of emerging pathways and novel techniques should facilitate exploration of biomarkers for improved staging and prognosis. METHODS: An observational study exploring predictive and prognostic biomarkers in a population-based, consecutive cohort of surgically treated colorectal cancers and resected colorectal liver metastases. Long-term outcomes will be cancer-specific survival, recurrence-free survival and overall survival at 5 years from diagnosis. Beyond routine clinicopathological and anthropometric characteristics and laboratory and biochemistry results, the project allows for additional blood samples and fresh-frozen tumour and normal tissue for investigation of circulating tumour cells (CTCs) and novel biomarkers (e.g. immune cells, microRNAs etc.). Tumour specimens will be investigated by immunohistochemistry in full slides. Extracted DNA/RNA will be analysed for genomic markers using specific PCR techniques and next-generation sequencing (NGS) panels. Flow cytometry will be used to characterise biomarkers in blood. Collaboration is open and welcomed, with particular interest in mutual opportunities for validation studies. STATUS AND PERSPECTIVES: The project is ongoing and recruiting at an expected rate of 120-150 patients per year, since January 2013. A project on circulating tumour cells (CTCs) has commenced, with analysis being prepared. Investigating molecular classes beyond the TNM staging is under way, including characteristics of microsatellite instability (MSI) and elevated microsatellite alterations in selected tetranucleotides (EMAST). Hot spot panels for known mutations in CRC are being investigated using NGS. Immune cell characteristics are being performed by IHC and flow cytometry in tumour and peripheral blood samples. The project has ethical approval (REK Helse Vest, #2012/742), is financially supported with a Ph.D.-Grant (EMAST project; Folke Hermansen Cancer Fund) and a CTC-project (Norwegian Research Council; O. Nordgard). The ACROBATICC clinical and molecular biobank repository will serve as a long-term source for novel exploratory analysis and invite collaborators for mutual validation of promising biomarker results. The project aims to generate results that can help better discern prognostic groups in stage II/III cancers; explore prognostic and predictive biomarkers, and help detail the biology of colorectal liver metastasis for better patient selection and tailored treatment. The project is registered at http://www.ClinicalTrials.gov NCT01762813. PMID- 27357109 TI - Loss of Lipid Virulence Factors Reduces the Efficacy of the BCG Vaccine. AB - Bacille Calmette-Guerin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. BCG comprises a number of substrains that exhibit genetic and biochemical differences. Whether and how these differences affect BCG efficacy remain unknown. Compared to other BCG strains, BCG-Japan, -Moreau, and -Glaxo are defective in the production of phthiocerol dimycocerosates (PDIMs) and phenolic glycolipids (PGLs), two lipid virulence factors. To determine if the loss of PDIMs/PGLs affects BCG efficacy, we constructed a PDIM/PGL-deficient strain of BCG-Pasteur by deleting fadD28, and compared virulence, immunogenicity, and protective efficacy in animal models. SCID mouse infection experiments showed that ?fadD28 was more attenuated than wild type (WT). The ?fadD28 and WT strains induced equivalent levels of antigen specific IFN-gamma by CD4(+) and CD8(+) T cells; however, ?fadD28 was less effective against Mycobacterium tuberculosis challenge in both BALB/c mice and guinea pigs. These results indicate that the loss of PIDMs/PGLs reduces the virulence and protective efficacy of BCG. Since the loss of PDIMs/PGLs occurs naturally in a subset of BCG strains, it also suggests that these strains may have been over-attenuated, which compromises their effectiveness. Our finding has important implications for current BCG programs and future vaccine development. PMID- 27357111 TI - Dumb-bell in the heart: rare case of biatrial myxoma with mitral regurgitation. AB - Cardiac myxomas are rare intracardiac tumors, and the majority are benign myxomas involving the left atrium. We report a case of the very rare occurrence of biatrial myxoma associated with mitral regurgitation, which was successfully treated. PMID- 27357110 TI - Genome-wide association study of prolactin levels in blood plasma and cerebrospinal fluid. AB - BACKGROUND: Prolactin is a polypeptide hormone secreted by the anterior pituitary gland that plays an essential role in lactation, tissue growth, and suppressing apoptosis to increase cell survival. Prolactin serves as a key player in many life-critical processes, including immune system and reproduction. Prolactin is also found in multiple fluids throughout the body, including plasma and cerebrospinal fluid (CSF). METHODS: In this study, we measured prolactin levels in both plasma and CSF, and performed a genome-wide association study. We then performed meta-analyses using METAL with a significance threshold of p < 5 * 10( 8) and removed SNPs where the direction of the effect was different between the two datasets. RESULTS: We identified 12 SNPs associated with increased prolactin levels in both biological fluids. CONCLUSIONS: Our efforts will help researchers understand how prolactin is regulated in both CSF and plasma, which could be beneficial in research for the immune system and reproduction. PMID- 27357112 TI - Preservation of the lung after 4-year compression by fibrous tumors of pleura. AB - Solitary fibrous tumor of the pleura is a neoplasm arising from mesenchymal tissue, which may cause dyspnea and cough. Computed tomography in a 72-year-old woman, who had been diagnosed with a 3-cm mass in the left upper lung 24 years previously, identified 15- and 10-cm tumors, with complete collapse of the lingula and lower lobe. The tumors were successfully excised with partial lung resection, and the collapsed lung was preserved. There was no recurrence or atelectasis at 4 years postoperatively. PMID- 27357113 TI - Good's syndrome: Is thymectomy the solution? Case report and literature review. AB - Good's syndrome is thymoma accompanied by immunodeficiency. A 69-year-old woman presented with recurrent chest infections, hypogammaglobulinemia, and radiological features of a thymoma. Immunoglobulin replacement therapy was not tolerated prior to surgery. Postoperative recovery was uneventful, and a Masaoka stage II type AB thymoma was confirmed on histology. One-year follow-up revealed no recurrence of the thymoma but the patient remained hypogammaglobulinemic and developed collagenous colitis. She declined immunoglobulin replacement therapy but remains under follow-up. Awareness of Good's syndrome to avoid overwhelming infection is emphasized. The finding of thymoma should prompt the thoracic surgeon to test for immunodeficiency. PMID- 27357114 TI - Thoracoscopic sympathicotomy in the treatment of palmar hyperhidrosis. AB - BACKGROUND: Primary hyperhidrosis interferes with social activities and requires an effective and safe treatment. We aimed to compare the therapeutic outcomes of unilateral single-port sympathicotomy and open surgery. METHODS: Forty patients with primary palmar hyperhidrosis underwent sympathicotomy; 20 had open surgery, and 20 had video-assisted thoracic surgery. Complete resection of the T1 to T4 ganglia was performed by open surgery, and cutting and cauterization of the sympathetic chain between the T2 and T3 ganglia in the dominant hand was undertaken using video-assisted thoracic surgery. The patients were followed up at 1, 3, 6, and 12 months after surgery. RESULTS: The mean operative times were 39.6 +/- 1.46 and 79.8 +/- 1.53 min in the video-assisted thoracic surgery and open surgery group, respectively. The mean hospitalization was 2.2 +/- 0.41 days after video-assisted thoracic surgery and 3.3 +/- 0.47 days after open surgery. Complications included delayed hemothorax, compensatory hyperhidrosis, and wound infection. The mean blood loss during surgery and time to return to work were significantly less in the video-assisted thoracic surgery group. Excessive sweating was completely alleviated in the dominant hand in all patients, and in the opposite hand in 60% and 65% of the video-assisted thoracic surgery and open surgery group, respectively. CONCLUSION: Single-port sympathicotomy between the T2 and T3 ganglia ipsilateral to the dominant hand is a safe, minimally invasive, and effective treatment for primary palmar hyperhidrosis. Alleviation of excessive sweating in the opposite hand can also be achieved in a large proportion of these patients. PMID- 27357115 TI - The use of sternal wedge osteotomy in pectus surgery: when is it necessary? AB - BACKGROUND: The Ravitch procedure is a well-established surgical procedure for correction of chest wall deformities. Sternal wedge osteotomy is an important part of this procedure. We studied the incidence of wedge osteotomy with respect to the type of chest wall deformity in patients undergoing surgical correction with the use of a recently developed chest wall stabilization system. METHODS: A total of 47 patients, 39 (83%) male and 8 (17%) female with a mean age of 14.9 +/ 2.1 years, underwent the Ravitch procedure. Twenty-four (51.1%) had pectus carinatum, 19 (40.4%) had pectus excavatum, and 4 (8.5%) had pectus arcuatum. A conventional or oblique sternal wedge osteotomy was performed as indicated, followed by chest wall stabilization using the MedXpert system. RESULTS: Of the 47 patients, 27 (57.4%) had a sternal wedge osteotomy. All cases of pectus arcuatum and redo cases underwent sternal wedge osteotomy. Pectus excavatum cases tended to have a greater incidence of wedge osteotomy compared to pectus carinatum cases (68.4% vs. 41.7%, p = 0.052). Patients with more resected ribs had a greater rate of wedge osteotomy (63.4%) compared to those with fewer resected ribs (16.7%, p = 0.043). CONCLUSIONS: A sternal wedge osteotomy is more commonly performed in patients with pectus excavatum compared to those with pectus carinatum. All redo and pectus arcuatum cases need a wedge osteotomy for proper correction. Wedge osteotomy is very likely in more aggressive corrections with more rib resections. PMID- 27357116 TI - Intracardiac lipoma in a child, causing right ventricular outflow obstruction. PMID- 27357117 TI - Contemporary endovascular treatment of type B aortic dissection in China. AB - OBJECTIVE: Endovascular stent-grafts have been used in China to treat type B aortic dissection since 1999, and there is a plethora of cohort studies in the contemporary literature. The aim of this review was to analyse the published results of endovascular treatment for type B aortic dissection in China. METHOD: A systematic literature review of all published literature from January 1999 to October 2014 on endovascular treatment of type B aortic dissection in China was undertaken using PubMed, Medline, and the Chinese National Knowledge Infrastructure databases. RESULTS: Seventy papers were retrieved (4 English, 66 Chinese) with a total of 4208 patients; 3396 (80.7%) were male, and the mean age ranged from 43 to 65 years. Procedural success was reported in 99.4% +/- 1.7%. Complications were reported in 14.6% +/- 11.1%, with major complications in 1.7% +/- 2.9%, and the most devastating neurologic complications in 1.1% +/- 2.2% (stroke 0.9% +/- 2.4%, paraplegia 1.5% +/- 0.7%). Postoperative endoleak occurred in 8.1% +/- 7.6%. The 30-day postoperative mortality was 2.4% +/- 3.3%. During follow-up, false-lumen thrombosis occurred in 92.1% +/- 11.7%. Reintervention was performed in 1.3% +/- 3.3%. The incidence of proximal and distal stent-graft induced new entry was 0.5% +/- 1.3% and 0.9% +/- 2.7%, respectively, with endoleak in 2.7% +/- 4.4% and mortality of 2.2% +/- 3.2%. CONCLUSIONS: Current evidence suggests that use of endovascular stent-grafts for type B aortic dissection in China is feasible and safe with low rates of perioperative complications and short-term mortality. However, a standardised reporting system and long-term follow-up data are lacking. PMID- 27357118 TI - Management of idiopathic chylopericardium in Pregnant Patient. AB - Idiopathic chylopericardium in pregnancy is extremely rare and poses difficulties in both decision-making and timing of surgery. A young lady who was 24-weeks pregnant presented with chylopericardium and increasing shortness of breath. Repeated nonsurgical interventions failed to resolve her pathology. She underwent thoracoscopic pericardial window formation and thoracic duct ligation, and made a satisfactory recovery. PMID- 27357119 TI - A proline-derived transannular N-cap for nucleation of short alpha-helical peptides. AB - We report herein a proline-derived transannular N-cap as a helix nucleating template in diverse bio-related peptide sequences via macrolactamization on resin. This approach takes advantage of synergistic stabilization effects of both N-capping properties of proline and substitution of a main chain hydrogen bond with a covalent bond. PMID- 27357120 TI - Anchored enrichment dataset for true flies (order Diptera) reveals insights into the phylogeny of flower flies (family Syrphidae). AB - BACKGROUND: Anchored hybrid enrichment is a form of next-generation sequencing that uses oligonucleotide probes to target conserved regions of the genome flanked by less conserved regions in order to acquire data useful for phylogenetic inference from a broad range of taxa. Once a probe kit is developed, anchored hybrid enrichment is superior to traditional PCR-based Sanger sequencing in terms of both the amount of genomic data that can be recovered and effective cost. Due to their incredibly diverse nature, importance as pollinators, and historical instability with regard to subfamilial and tribal classification, Syrphidae (flower flies or hoverflies) are an ideal candidate for anchored hybrid enrichment-based phylogenetics, especially since recent molecular phylogenies of the syrphids using only a few markers have resulted in highly unresolved topologies. Over 6200 syrphids are currently known and uncovering their phylogeny will help us to understand how these species have diversified, providing insight into an array of ecological processes, from the development of adult mimicry, the origin of adult migration, to pollination patterns and the evolution of larval resource utilization. RESULTS: We present the first use of anchored hybrid enrichment in insect phylogenetics on a dataset containing 30 flower fly species from across all four subfamilies and 11 tribes out of 15. To produce a phylogenetic hypothesis, 559 loci were sampled to produce a final dataset containing 217,702 sites. We recovered a well resolved topology with bootstrap support values that were almost universally >95 %. The subfamily Eristalinae is recovered as paraphyletic, with the strongest support for this hypothesis to date. The ant predators in the Microdontinae are sister to all other syrphids. Syrphinae and Pipizinae are monophyletic and sister to each other. Larval predation on soft-bodied hemipterans evolved only once in this family. CONCLUSIONS: Anchored hybrid enrichment was successful in producing a robustly supported phylogenetic hypothesis for the syrphids. Subfamilial reconstruction is concordant with recent phylogenetic hypotheses, but with much higher support values. With the newly designed probe kit this analysis could be rapidly expanded with further sampling, opening the door to more comprehensive analyses targeting problem areas in syrphid phylogenetics and ecology. PMID- 27357121 TI - Impeding (99)Tc(IV) mobility in novel waste forms. AB - Technetium ((99)Tc) is an abundant, long-lived radioactive fission product whose mobility in the subsurface is largely governed by its oxidation state. Tc immobilization is crucial for radioactive waste management and environmental remediation. Tc(IV) incorporation in spinels has been proposed as a novel method to increase Tc retention in glass waste forms during vitrification. However, experiments under high-temperature and oxic conditions show reoxidation of Tc(IV) to volatile pertechnetate, Tc(VII). Here we examine this problem with ab initio molecular dynamics simulations and propose that, at elevated temperatures, doping with first row transition metal can significantly enhance Tc retention in magnetite in the order Co>Zn>Ni. Experiments with doped spinels at 700 degrees C provide quantitative confirmation of the theoretical predictions in the same order. This work highlights the power of modern, state-of-the-art simulations to provide essential insights and generate theory-inspired design criteria of complex materials at elevated temperatures. PMID- 27357122 TI - Structural changes in femoral bone microstructure of female rabbits after intramuscular administration of quercetin. AB - BACKGROUND: Quercetin is one of the best known flavonoids being present in a variety of fruits and vegetables. It has cardioprotective, anticarcinogenic, antioxidant, anti-inflammatory and antiapoptotic properties. Some studies suggest that quercetin has protective effects on bone. However, its influence on qualitative and quantitative histological characteristics of compact bone is still unknown. In our study, 12 clinically healthy five-month-old female rabbits were divided into four groups of three animals each. Quercetin was applied intramuscularly in various concentrations; 10 ug/kg body weight (bw) in the E1 group, 100 ug/kg bw in the E2 group, and 1000 ug/kg bw in the E3 group for 90 days, 3 times per week. Three rabbits without exposure to quercetin served as a control (C) group. Differences in femoral bone microstructure among groups were evaluated. RESULTS: Qualitative histological characteristics of compact bone differed between rabbits from the E1 and E2 groups. Primary vascular longitudinal bone tissue was not found in some areas near the endosteal surface due to increased endocortical bone resorption. In addition, periosteal border of rabbits from the E1 group was composed of a thicker layer of primary vascular longitudinal bone tissue than in the other groups. In all groups of rabbits administered quercetin, a lower density of secondary osteons was observed. Histomorphometrical evaluations showed significantly decreased sizes of the primary osteons' vascular canals in individuals from the E1 and E2 groups. Secondary osteons were significantly smaller in rabbits from the E1, E2, E3 groups when compared to the C group. Cortical bone thickness was significantly increased in females from the E1 and E2 groups. CONCLUSIONS: The results indicate that quercetin has not only a positive dose-response on qualitative and quantitative histological characteristics of the compact bone of female rabbits as it would be expected. PMID- 27357123 TI - Factors influencing the uptake of neonatal bereavement support services - Findings from two tertiary neonatal centres in the UK. AB - BACKGROUND: Research on perinatal bereavement services is limited. The aim of the study was to compare the uptake of bereavement support services between two tertiary neonatal units (NNU), and to investigate influencing factors. METHOD: The medical and bereavement records of all neonatal deaths were studied from January 2006 to December 2011. Data collected included parent and baby characteristics, mode of death, consent for autopsy and bereavement follow-up. The categorical data were compared by chi-square or Fisher's exact test and continuous data by Wilcoxon signed-rank test; a multivariable regression analysis was performed using STATA 12.0. RESULTS: The neonatal deaths of 297 babies (182 in NNU1 and 115 in NNU2) with full datasets were analysed. Baby characteristics were similar between units except for lower median gestational age in NNU1 (p = 0.03). Significantly more NNU1 parents were non-Caucasian (p < 0.01), from lower socio-economic status (p = 0.01) and had previous stillbirth/miscarriage (p = 0.03). More babies had care withdrawn in NNU2 (p < 0.01). A significantly higher proportion of parents from NNU1 (61 %) attended bereavement follow-up compared to NNU2 (34 %; p < 0.01). On multivariable analysis, significantly more parents who were married or co-habiting (p = 0.02) and consented for an autopsy (p = 0.01) attended bereavement services. CONCLUSION: Uptake of bereavement services varied between the two NNUs, which could be due to differences in the ethnic and socio economic mix of the population. Significantly more parents who were married or co habiting, or consented for autopsy, attended bereavement follow up services. PMID- 27357125 TI - Beyond Poisson-Boltzmann: fluctuations and fluid structure in a self-consistent theory. AB - Poisson-Boltzmann (PB) theory is the classic approach to soft matter electrostatics and has been applied to numerous physical chemistry and biophysics problems. Its essential limitations are in its neglect of correlation effects and fluid structure. Recently, several theoretical insights have allowed the formulation of approaches that go beyond PB theory in a systematic way. In this topical review, we provide an update on the developments achieved in the self consistent formulations of correlation-corrected Poisson-Boltzmann theory. We introduce a corresponding system of coupled non-linear equations for both continuum electrostatics with a uniform dielectric constant, and a structured solvent-a dipolar Coulomb fluid-including non-local effects. While the approach is only approximate and also limited to corrections in the so-called weak fluctuation regime, it allows us to include physically relevant effects, as we show for a range of applications of these equations. PMID- 27357124 TI - Psychological stress and short-term hospitalisations or death in patients with heart failure. AB - OBJECTIVE: Standard predictors do not fully explain variations in the frequency and timing of heart failure (HF) adverse events (AEs). Psychological stress can trigger acute cardiovascular (CV) events, but it is not known whether stress can precipitate AEs in patients with HF. We investigated prospective associations of psychological stress with AEs in patients with HF. METHODS: 144 patients with HF (77% male; 57.5+/-11.5, range 23-87 years, left ventricular ejection fraction <=40%) were longitudinally evaluated for psychological stress (Perceived Stress Scale) and AEs (CV hospitalisations/death) at 2-week intervals for 3 months and at 9-month follow-up. RESULTS: 42 patients (29.2%) had at least one CV hospitalisation and nine (6.3%) died. Patients reporting high average perceived stress across study measurements had a higher likelihood of AEs during the study period compared with those with lower stress (odds ratio=1.10, 95% confidence interval=1.04 to 1.17). In contrast to average levels, increases in stress did not predict AEs (p=0.96). Perceived stress was elevated after a CV hospitalisation (B=2.70, standard error (SE)=0.93, p=0.004) suggesting that CV hospitalisations increase stress. Subsequent analysis indicated that 24 of 38 (63%) patients showed a stress increase following hospitalisation. However, a prospective association between stress and AEs was present when accounting for prior hospitalisations (B=2.43, SE=1.23, p=0.05). CONCLUSIONS: Sustained levels of perceived stress are associated with increased risk of AEs, and increased distress following hospitalisation occurs in many, but not all, patients with HF. Patients with chronically high stress may be an important target group for HF interventions aimed at reducing hospitalisations. PMID- 27357126 TI - Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. AB - BACKGROUND: Advances in cell culture media have led to a shift in in vitro fertilisation (IVF) practice from cleavage stage embryo transfer to blastocyst stage transfer. The rationale for blastocyst transfer is to improve both uterine and embryonic synchronicity and enable self selection of viable embryos, thus resulting in better live birth rates. OBJECTIVES: To determine whether blastocyst stage (day 5 to 6) embryo transfers improve the live birth rate, and other associated outcomes, compared with cleavage stage (day 2 to 3) embryo transfers. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library; 2016, Issue 4), MEDLINE, EMBASE, PsycINFO, CINAHL, and Bio extracts from inception to 4th April 2016. We also searched registers of ongoing trials and the reference lists of studies retrieved. SELECTION CRITERIA: We included randomised controlled trials (RCTs) which compared the effectiveness of blastocyst versus cleavage stage transfers. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Our primary outcomes were live birth and cumulative clinical pregnancy rates. Secondary outcomes were clinical pregnancy, multiple pregnancy, high order pregnancy, miscarriage, failure to transfer embryos, and embryo freezing. We assessed the overall quality of the evidence for the main comparisons using GRADE methods. MAIN RESULTS: We included 27 RCTs (4031 couples or women).The live birth rate following fresh transfer was higher in the blastocyst transfer group (odds ratio (OR) 1.48, 95% confidence interval (CI) 1.20 to 1.82; 13 RCTs, 1630 women, I(2) = 45%, low quality evidence) following fresh transfer. This suggests that if 29% of women achieve live birth after fresh cleavage stage transfer, between 32% and 42% would do so after fresh blastocyst stage transfer.There was no evidence of a difference between the groups in rates per couple of cumulative pregnancy following fresh and frozen-thawed transfer after one oocyte retrieval (OR 0.89, 95% CI 0.64 to 1.22; 5 RCTs, 632 women, I(2) = 71%, very low quality evidence).The clinical pregnancy rate was also higher in the blastocyst transfer group, following fresh transfer (OR 1.30, 95% CI 1.14 to 1.47; 27 RCTs, 4031 women, I(2) = 56%, moderate quality evidence). This suggests that if 36% of women achieve clinical pregnancy after fresh cleavage stage transfer, between 39% and 46% would do so after fresh blastocyst stage transfer.There was no evidence of a difference between the groups in rates of multiple pregnancy (OR 1.05, 95% CI 0.83 to 1.33; 19 RCTs, 3019 women, I(2) = 30%, low quality evidence), or miscarriage (OR 1.15, 95% CI 0.88 to 1.50; 18 RCTs, 2917 women, I(2) = 0%, low quality evidence). These data are incomplete as under 70% of studies reported these outcomes.Embryo freezing rates were lower in the blastocyst transfer group (OR 0.48, 95% CI 0.40 to 0.57; 14 RCTs, 2292 women, I(2) = 84%, low quality evidence). This suggests that if 60% of women have embryos frozen after cleavage stage transfer, between 37% and 46% would do so after blastocyst stage transfer. Failure to transfer any embryos was higher in the blastocyst transfer group (OR 2.50, 95% CI 1.76 to 3.55; 17 RCTs, 2577 women, I(2) = 36%, moderate quality evidence). This suggests that if 1% of women have no embryos transferred in (planned) fresh cleavage stage transfer, between 2% and 4% will have no embryos transferred in (planned) fresh blastocyst stage transfer.The evidence was of low quality for most outcomes. The main limitation was serious risk of bias, associated with failure to describe acceptable methods of randomisation, and unclear or high risk of attrition bias. AUTHORS' CONCLUSIONS: There is low quality evidence for live birth and moderate quality evidence for clinical pregnancy that fresh blastocyst stage transfer is associated with higher rates than fresh cleavage stage transfer. There was no evidence of a difference between the groups in cumulative pregnancy rates derived from fresh and frozen thawed cycles following a single oocyte retrieval, but the evidence for this outcome was very low quality. Thus, although there is a benefit favouring blastocyst transfer in fresh cycles, it remains unclear whether the day of transfer impacts on cumulative live birth and pregnancy rates. Future RCTs should report rates of live birth, cumulative live birth, and miscarriage to enable couples or women undergoing assisted reproductive technology (ART) and service providers to make well informed decisions on the best treatment option available. PMID- 27357127 TI - Variable responses of human microbiomes to dietary supplementation with resistant starch. AB - BACKGROUND: The fermentation of dietary fiber to various organic acids is a beneficial function provided by the microbiota in the human large intestine. In particular, butyric acid contributes to host health by facilitating maintenance of epithelial integrity, regulating inflammation, and influencing gene expression in colonocytes. We sought to increase the concentration of butyrate in 20 healthy young adults through dietary supplementation with resistant starch (unmodified potato starch-resistant starch (RS) type 2). METHODS: Fecal samples were collected from individuals to characterize butyrate concentration via liquid chromatography and composition of the microbiota via surveys of 16S rRNA-encoding gene sequences from the Illumina MiSeq platform. Random Forest and LEfSe analyses were used to associate responses in butyrate production to features of the microbiota. RESULTS: RS supplementation increased fecal butyrate concentrations in this cohort from 8 to 12 mmol/kg wet feces, but responses varied widely between individuals. Individuals could be categorized into three groups based upon butyrate concentrations before and during RS: enhanced, high, and low (n = 11, 3, and 6, respectively). Fecal butyrate increased by 67 % in the enhanced group (from 9 to 15 mmol/kg), while it remained >=11 mmol/kg in the high group and <=8 mmol/kg in the low group. Microbiota analyses revealed that the relative abundance of RS-degrading organisms-Bifidobacterium adolescentis or Ruminococcus bromii-increased from ~2 to 9 % in the enhanced and high groups, but remained at ~1.5 % in the low group. The lack of increase in RS-degrading bacteria in the low group may explain why there was no increase in fecal butyrate in response to RS. The microbiota of individuals in the high group were characterized by an elevated abundance of the butyrogenic microbe Eubacterium rectale (~6 % in high vs. 3 % in enhanced and low groups) throughout the study. CONCLUSIONS: We document the heterogeneous responses in butyrate concentrations upon RS supplementation and identify characteristic of the microbiota that appear to underlie this variation. This study complements and extends other studies that call for personalized approaches to manage beneficial functions provided by gut microbiomes. PMID- 27357129 TI - A high-resolution palaeoenvironmental record from carbonate deposits in the Roman aqueduct of Patara, SW Turkey, from the time of Nero. AB - An inscription on the supporting wall of the inverted siphon of the aqueduct of the ancient Roman city of Patara, SW Turkey, explains how the wall collapsed during an earthquake and was subsequently restored. Carbonate deposits formed inside the aqueduct channel show cyclic stable isotope changes representing 17 years of deposition. This sequence, together with the text of the inscription, allows dating the earthquake to 68 AD and the original inauguration of the aqueduct to the winter of 51/52 AD. Thus, the carbonate deposits represent a high resolution record of palaeotemperature and precipitation for SW Turkey covering the complete reign of the Emperor Nero. The period shows a cooling and drying trend after an initial warm and more humid period, interrupted by a few anomalous years. These 2 cm of calcite highlight the significance of carbonate deposits in ancient water supply systems as a high-resolution archive for palaeoclimate, palaeoseismology and archaeology. PMID- 27357128 TI - Exposure to vector-borne pathogens in candidate blood donor and free-roaming dogs of northeast Italy. AB - BACKGROUND: Many vector-borne pathogens including viruses, bacteria, protozoa and nematodes occur in northeast Italy, representing a potential threat to animal and human populations. Little information is available on the circulation of the above vector-borne pathogens in dogs. This work aims to (i) assess exposure to and circulation of pathogens transmitted to dogs in northeast Italy by ticks, sandflies, and mosquitoes, and (ii) drive blood donor screening at the newly established canine blood bank of the Istituto Zooprofilattico Sperimentale delle Venezie. METHODS: Blood samples from 150 privately-owned canine candidate blood donors and 338 free-roaming dogs were screened by serology (IFA for Leishmania infantum, Ehrlichia canis, Anaplasma phagocythophilum, Babesia canis, Rickettsia conorii, R. rickettsii), microscopic blood smear examination, and blood filtration for Dirofilaria spp. All candidate donors and seropositive free roaming dogs were tested by PCR for L. infantum, E. canis, A. phagocythophilum, Babesia/Theileria and Rickettsia spp. The dogs had no clinical signs at the time of sampling. RESULTS: Overall, 40 candidate donors (26.7 %) and 108 free-roaming dogs (32 %) were seroreactive to at least one vector-borne pathogen. Seroprevalence in candidate donors vs free-roaming dogs was: Leishmania infantum 6.7 vs 7.1 %; Anaplasma phagocytophilum 4.7 vs 3.3 %; Babesia canis 1.3 vs 2.7 %; Ehrlichia canis none vs 0.9 %; Rickettsia conorii 16 vs 21.3 % and R. rickettsii 11 vs 14.3 %. Seroreactivity to R. rickettsii, which is not reported in Italy, is likely a cross-reaction with other rickettsiae. Filariae, as Dirofilaria immitis (n = 19) and D. repens (n = 2), were identified in free-roaming dogs only. No significant differences were observed between candidate donors and free-roaming dogs either in the overall seroprevalence of vector-borne pathogens or for each individual pathogen. All PCRs and smears performed on blood were negative. CONCLUSIONS: This study demonstrated that dogs are considerably exposed to vector borne pathogens in northeast Italy. Although the dog owners reported regularly using ectoparasiticides against fleas and ticks, their dogs had similar exposure to vector-borne pathogens as free-roaming dogs. This prompts the need to improve owner education on the use of insecticidal and repellent compounds in order to reduce the risk of arthropod bites and exposure to vector-borne pathogens. Based on the absence of pathogens circulating in the blood of healthy dogs, the risk of transmission of these pathogens by blood transfusion seems to be low, depending also on the sensitivity of the tests used for screening. PMID- 27357130 TI - Quantifying cadherin mechanotransduction machinery assembly/disassembly dynamics using fluorescence covariance analysis. AB - Quantifying multi-molecular complex assembly in specific cytoplasmic compartments is crucial to understand how cells use assembly/disassembly of these complexes to control function. Currently, biophysical methods like Fluorescence Resonance Energy Transfer and Fluorescence Correlation Spectroscopy provide quantitative measurements of direct protein-protein interactions, while traditional biochemical approaches such as sub-cellular fractionation and immunoprecipitation remain the main approaches used to study multi-protein complex assembly/disassembly dynamics. In this article, we validate and quantify multi protein adherens junction complex assembly in situ using light microscopy and Fluorescence Covariance Analysis. Utilizing specific fluorescently-labeled protein pairs, we quantified various stages of adherens junction complex assembly, the multiprotein complex regulating epithelial tissue structure and function following de novo cell-cell contact. We demonstrate: minimal cadherin catenin complex assembly in the perinuclear cytoplasm and subsequent localization to the cell-cell contact zone, assembly of adherens junction complexes, acto myosin tension-mediated anchoring, and adherens junction maturation following de novo cell-cell contact. Finally applying Fluorescence Covariance Analysis in live cells expressing fluorescently tagged adherens junction complex proteins, we also quantified adherens junction complex assembly dynamics during epithelial monolayer formation. PMID- 27357131 TI - Prognosis prediction of non-enhancing T2 high signal intensity lesions in glioblastoma patients after standard treatment: application of dynamic contrast enhanced MR imaging. AB - OBJECTIVES: To identify candidate imaging biomarkers for early disease progression in glioblastoma multiforme (GBM) patients by analysis of dynamic contrast-enhanced (DCE) MR parameters of non-enhancing T2 high signal intensity (SI) lesions. METHODS: Forty-nine GBM patients who had undergone preoperative DCE MR imaging and received standard treatment were retrospectively included. According to the Response Assessment in Neuro-Oncology criteria, patients were classified into progression (n = 21) or non-progression (n = 28) groups. We analysed the pharmacokinetic parameters of Ktrans, Ve and Vp within non-enhancing T2 high SI lesions of each tumour. The best percentiles of each parameter from cumulative histograms were identified by the area under the receiver operating characteristic curve (AUC) and were compared using multivariate stepwise logistic regression. RESULTS: For the differentiation of early disease progression, the highest AUC values were found in the 99th percentile of Ktrans (AUC 0.954), the 97th percentile of Ve (AUC 0.815) and the 94th percentile of Vp (AUC 0.786) (all p < 0.05). The 99th percentile of Ktrans was the only significant independent variable from the multivariate stepwise logistic regression (p = 0.002). CONCLUSIONS: We found that the Ktrans of non-enhancing T2 high SI lesions in GBM patients holds potential as a candidate prognostic marker in future prospective studies. KEY POINTS: * DCE MR imaging provides candidate prognostic marker of GBM after standard treatment. * Cumulative histogram was applied to include entire non-enhancing T2 high SI lesions. * The 99th percentile value of Ktrans was the most likely potential biomarker. PMID- 27357133 TI - Indefinite Plasmonic Beam Engineering by In-plane Holography. AB - Recent advances in controlling the optical phase at the sub-wavelength scale by meta-structures offer unprecedented possibilities in the beam engineering, holograms, and even invisible cloaks. In despite of developments of plasmonic beam engineering for definite beams, here, we proposed a new holographic strategy by in-plane diffraction process to access indefinite plasmonic beams, where a counterintuitive oscillating beam was achieved at a free metal surface that is against the common recognition of light traveling. Beyond the conventional hologram, our approach emphasizes on the phase correlation on the target, and casts an in-depth insight into the beam formation as a kind of long depth-of field object. Moreover, in contrast to previous plasmonic holography with space light as references, our approach is totally fulfilled in a planar dimension that offers a thoroughly compact manipulation of the plasmonic near-field and suggests new possibilities in nanophotonic designs. PMID- 27357132 TI - Forensic use of the Greulich and Pyle atlas: prediction intervals and relevance. AB - OBJECTIVE: The Greulich and Pyle (GP) atlas is one of the most frequently used methods of bone age (BA) estimation. Our aim is to assess its accuracy and to calculate the prediction intervals at 95% for forensic use. METHODS: The study was conducted on a multi-ethnic sample of 2614 individuals (1423 boys and 1191 girls) referred to the university hospital of Marseille (France) for simple injuries. Hand radiographs were analysed using the GP atlas. Reliability of GP atlas and agreement between BA and chronological age (CA) were assessed and prediction intervals at 95% were calculated. RESULTS: The repeatability was excellent and the reproducibility was good. Pearson's linear correlation coefficient between CA and BA was 0.983. The mean difference between BA and CA was -0.18 years (boys) and 0.06 years (girls). The prediction interval at 95% for CA was given for each GP category and ranged between 1.2 and more than 4.5 years. CONCLUSION: The GP atlas is a reproducible and repeatable method that is still accurate for the present population, with a high correlation between BA and CA. The prediction intervals at 95% are wide, reflecting individual variability, and should be known when the method is used in forensic cases. KEY POINTS: * The GP atlas is still accurate at the present time. * There is a high correlation between bone age and chronological age. * Individual variability must be known when GP is used in forensic cases. * Prediction intervals (95%) are large; around 4 years after 10 year olds. PMID- 27357134 TI - Primary Lingual Colonic-Type Adenocarcinoma: A Rare and Emerging Distinct Entity! AB - Primary colonic-type adenocarcinoma involving the tongue (CTAT) is exquisitely rare, with only four cases having been reported in the literature. We report the case of a 53-year-old woman with an anterior (oral) tongue mass. A review of literature was performed. Histomorphologic features were evaluated with standard hematoxylin and eosin stained sections. Ancillary testing was performed. The mass consisted of invasive adenocarcinoma associated with "dirty necrosis", akin to the phenotype seen in colorectal adenocarcinoma. By immunohistochemistry, the tumor cells were positive for AE1/3, CDX2, CK20, SATB2 and beta-catenin. This was initially felt to represent a metastatic colorectal adenocarcinoma but subsequent PET/CT and colonoscopy examination were negative for colorectal mass, excluding the possibility of a metastasis and confirming a diagnosis of CTAT. We raise awareness of the existence of this entity and recommend that metastatic disease be excluded before rendering a diagnosis of CTAT. PMID- 27357135 TI - Prognostic value of D-dimer in elderly patients with Pulmonary Embolism. AB - In a general population with acute Pulmonary Embolism (PE) elevated D-dimer concentrations associate with increased mortality. The aim of the study was to assess the ability of D-dimer to predict 30 and 90-days mortality in elderly patients with acute PE. Hemodynamically stable patients aged >=65 years old with confirmed PE were included in this retrospective cohort study. A pulmonary computerized tomography angiography scan, D-dimer concentrations, simplified Pulmonary Embolism Severity Index (sPESI) variables and vital status were available for all patients. The study included 154 confirmed cases of PE (23.5 % of suspected), median age 79.1 years. D-dimer was higher in patients dead than in those alive at 30 (median 14,547 vs. 8340 ng/mL, p = 0.05) and 90 days (13,604 vs. 7973 ng/mL, p = 0.013). When adding D-dimer to sPESI, the discriminant capacity to predict mortality within 30 and 90 days was increased by 0.080 and 0.089, respectively. The contribution of D-dimer to the discriminating ability was NRI = 0.286 (95 % CI -0.198 to 0.770, p value: 0.247) at 30 days and NRI = 0.605 (95 % CI 0.223-0.988, p-value: 0.002) at 90 days.D-dimer concentration was associated with 30 and 90-days mortality and showed a higher discriminant capacity than sPESI alone to predict 90-days mortality. Adding D-dimer concentrations to sPESI score seems to improve its prognostic ability, supporting multivariable risk models as the best approach to estimate prognosis in elderly patients with PE. PMID- 27357137 TI - Sepsis and septic shock. PMID- 27357138 TI - Meetings of the mind! PMID- 27357136 TI - Psgl-1 Deficiency is Protective against Stroke in a Murine Model of Lupus. AB - Systemic lupus erythematosus (SLE) is associated with an elevated risk of vascular complications, including premature stroke. Therapies targeting leukocyte recruitment may be beneficial in reducing vascular complications associated with SLE. Lupus was induced in female wild-type (WT) and P-selectin glycoprotein ligand-1 deficient (Psgl-1(-/-)) mice with pristane. Stroke was induced following photochemical injury to the middle cerebral artery (MCA). Stroke size was increased in pristane-treated WT mice compared to non-pristane-treated WT controls. However, stroke size was not increased in pristane-treated Psgl-1(-/-) mice compared to controls, despite evidence of increased nephritis in Psgl-1(-/-) mice. Pristane-treated WT mice showed elevated anti-dsDNA, anti-snRNP, CXCL1, and MCP-1 levels compared to untreated mice; however levels of anti-snRNP, MCP-1, and CXCL1 were reduced in pristane-treated Psgl-1(-/-) mice compared to pristane treated WT mice. Infiltration of neutrophils and macrophages at the cerebral infarction site were reduced in pristane-treated Psgl-1(-/-) mice compared to pristane-treated WT mice. In conclusion, the increase in stroke size associated with lupus is prevented by Psgl-1 deficiency while nephritis is exacerbated. Therapies targeting Psgl-1 may be useful in the management of SLE patients at high risk of acute vascular complications although elucidation of downstream pathways will be necessary to identify targets that do not promote nephritis. PMID- 27357139 TI - Reflections: Spirituality and Cancer Researchers. AB - Spirituality is increasingly acknowledged as an essential element to consider within care for cancer and other chronic health conditions. As our colleagues in frontline healthcare roles integrate these concepts into their professional practice, it seems timely for the cancer research community to reflect on the place of spirituality within our work. This reflections article discusses challenges and opportunities for researchers considering spirituality in their own work roles and within broader discussions about health needs, care and research agendas. PMID- 27357140 TI - Training Primary Health Professionals in Breast Cancer Prevention: Evidence and Experience from Mexico. AB - To analyze the key successful factors of a national educational strategy for early breast cancer detection developed in Mexico for primary health care personnel from 2008 to 2014, an educational strategy to train physicians, nurses, health promoters, and medical students from local ministries of health with a competency-based approach was developed and implemented using diverse educational modalities, face-to-face, blended, and a massive open online course (MOOC). Formative and summative evaluations were used during the implementation of the course. A total of 19,563 health professionals were trained from 2008 to 2014. The graduation rate, an average of all educational modalities, was 91 %, much higher than those previously reported in the literature. The factors that might have influenced this success were (1) the training strategy, which was designed according to the characteristics and specific needs of the target groups; (2) the political will and commitment of the country's health authorities; (3) the technological and educational models used; and (4) the punctual follow-up of participants. This study shows that carefully designed educational interventions can improve service professionals' competencies and that regardless of the modality, face-to-face, blended learning, or MOOC, high graduation rates can be achieved. Further evaluation is required to demonstrate that the competencies remained in all target groups after 6 months of the intervention and that the women served by the trained personnel were provided accurate information and timely diagnoses of breast cancer. PMID- 27357142 TI - Stem cells for all ages, yet hostage to aging. PMID- 27357141 TI - Antimicrobial Potential of Thiodiketopiperazine Derivatives Produced by Phoma sp., an Endophyte of Glycyrrhiza glabra Linn. AB - During the screening of endophytes obtained from Glycyrrhiza glabra Linn., the extract from a fungal culture designated as GG1F1 showed significant antimicrobial activity. The fungus was identified as a species of the genus Phoma and was most closely related to Phoma cucurbitacearum. The chemical investigation of the GG1F1 extract led to the isolation and characterization of two thiodiketopiperazine derivatives. Both the compounds inhibited the growth of several bacterial pathogens especially that of Staphylococcus aureus and Streptococcus pyogenes, with IC50 values of less than 10 MUM. The compounds strongly inhibited biofilm formation in both the pathogens. In vitro time kill kinetics showed efficient bactericidal activity of these compounds. The compounds were found to act synergistically with streptomycin while producing varying effects in combination with ciprofloxacin and ampicillin. The compounds inhibited bacterial transcription/translation in vitro, and also inhibited staphyloxanthin production in S. aureus. Although similar in structure, they differed significantly in some of their properties, particularly the effect on the expression of pathogenecity related genes in S. aureus at sub-lethal concentrations. Keeping in view the antimicrobial potential of these compounds, it would be needful to scale up the production of these compounds through fermentation technology and further explore their potential as antibiotics using in vivo models. PMID- 27357143 TI - Cutaneous sarcoidosis in a melanoma patient under Ipilimumab therapy. PMID- 27357144 TI - Twenty years of Hendra virus: laboratory submission trends and risk factors for infection in horses. AB - Hendra virus (HeV) was first described in 1994 in an outbreak of acute and highly lethal disease in horses and humans in Australia. Equine cases continue to be diagnosed periodically, yet the predisposing factors for infection remain unclear. We undertook an analysis of equine submissions tested for HeV by the Queensland government veterinary reference laboratory over a 20-year period to identify and investigate any patterns. We found a marked increase in testing from July 2008, primarily reflecting a broadening of the HeV clinical case definition. Peaks in submissions for testing, and visitations to the Government HeV website, were associated with reported equine incidents. Significantly differing between year HeV detection rates in north and south Queensland suggest a fundamental difference in risk exposure between the two regions. The statistical association between HeV detection and stockhorse type may suggest that husbandry is a more important risk determinant than breed per se. The detection of HeV in horses with neither neurological nor respiratory signs poses a risk management challenge for attending veterinarians and laboratory staff, reinforcing animal health authority recommendations that appropriate risk management strategies be employed for all sick horses, and by anyone handling sick horses or associated biological samples. PMID- 27357145 TI - Site-Specific and High-Loading Immobilization of Proteins by Using Cohesin Dockerin and CBM-Cellulose Interactions. AB - Immobilization of enzymes enhances their properties for application in industrial processes as reusable and robust biocatalysts. Here, we developed a new immobilization method by mimicking the natural cellulosome system. A group of cohesin and carbohydrate-binding module (CBM)-containing scaffoldins were genetically engineered, and their length was controlled by cohesin number. To use green fluorescent protein (GFP) as an immobilization model, its C-terminus was fused with a dockerin domain. GFP was able to specifically bind to scaffoldin via cohesin-dockerin interaction, while the scaffoldin could attach to cellulose by CBM-cellulose interaction. Our results showed that this mild and convenient approach was able to achieve site-specific immobilization, and the maximum GFP loading capacity reached ~0.508 MUmol/g cellulose. PMID- 27357146 TI - Assessing generative braille responding following training in a matching-to sample format. AB - We evaluated the effects of teaching sighted college students to select printed text letters given a braille sample stimulus in a matching-to-sample (MTS) format on the emergence of untrained (a) construction of print characters given braille samples, (b) construction of braille characters given print samples, (c) transcription of print characters given braille sample sentences, and (d) vocal reading given braille sample passages. The results demonstrated the generative development of these repertoires given MTS instruction. PMID- 27357147 TI - Contamination of DNase Preparations Confounds Analysis of the Role of DNA in Alum Adjuvanted Vaccines. AB - Aluminum salt (alum) adjuvants have been used for many years as adjuvants for human vaccines because they are safe and effective. Despite its widespread use, the means by which alum acts as an adjuvant remains poorly understood. Recently, it was shown that injected alum is rapidly coated with host chromatin within mice. Experiments suggested that the host DNA in the coating chromatin contributed to alum's adjuvant activity. Some of the experiments used commercially purchased DNase and showed that coinjection of these DNase preparations with alum and Ag reduced the host's immune response to the vaccine. In this study, we report that some commercial DNase preparations are contaminated with proteases. These proteases are responsible for most of the ability of DNase preparations to inhibit alum's adjuvant activity. Nevertheless, DNase somewhat reduces responses to some Ags with alum. The effect of DNase is independent of its ability to cleave DNA, suggesting that alum improves CD4 responses to Ag via a pathway other than host DNA sensing. PMID- 27357148 TI - Inhibition of Phagocytic Killing of Escherichia coli in Drosophila Hemocytes by RNA Chaperone Hfq. AB - An RNA chaperone of Escherichia coli, called host factor required for phage Qbeta RNA replication (Hfq), forms a complex with small noncoding RNAs to facilitate their binding to target mRNA for the alteration of translation efficiency and stability. Although the role of Hfq in the virulence and drug resistance of bacteria has been suggested, how this RNA chaperone controls the infectious state remains unknown. In the present study, we addressed this issue using Drosophila melanogaster as a host for bacterial infection. In an assay for abdominal infection using adult flies, an E. coli strain with mutation in hfq was eliminated earlier, whereas flies survived longer compared with infection with a parental strain. The same was true with flies deficient in humoral responses, but the mutant phenotypes were not observed when a fly line with impaired hemocyte phagocytosis was infected. The results from an assay for phagocytosis in vitro revealed that Hfq inhibits the killing of E. coli by Drosophila phagocytes after engulfment. Furthermore, Hfq seemed to exert this action partly through enhancing the expression of sigma(38), a stress-responsive sigma factor that was previously shown to be involved in the inhibition of phagocytic killing of E. coli, by a posttranscriptional mechanism. Our study indicates that the RNA chaperone Hfq contributes to the persistent infection of E. coli by maintaining the expression of bacterial genes, including one coding for sigma(38), that help bacteria evade host immunity. PMID- 27357149 TI - Resident T Cells Are Unable To Control Herpes Simplex Virus-1 Activity in the Brain Ependymal Region during Latency. AB - HSV type 1 (HSV-1) is one of the leading etiologies of sporadic viral encephalitis. Early antiviral intervention is crucial to the survival of herpes simplex encephalitis patients; however, many survivors suffer from long-term neurologic deficits. It is currently understood that HSV-1 establishes a latent infection within sensory peripheral neurons throughout the life of the host. However, the tissue residence of latent virus, other than in sensory neurons, and the potential pathogenic consequences of latency remain enigmatic. In the current study, we characterized the lytic and latent infection of HSV-1 in the CNS in comparison with the peripheral nervous system following ocular infection in mice. We used RT-PCR to detect latency-associated transcripts and HSV-1 lytic cycle genes within the brain stem, the ependyma (EP), containing the limbic and cortical areas, which also harbor neural progenitor cells, in comparison with the trigeminal ganglia. Unexpectedly, HSV-1 lytic genes, usually identified during acute infection, are uniquely expressed in the EP 60 d postinfection when animals are no longer suffering from encephalitis. An inflammatory response was also mounted in the EP by the maintenance of resident memory T cells. However, EP T cells were incapable of controlling HSV-1 infection ex vivo and secreted less IFN gamma, which correlated with expression of a variety of exhaustion-related inhibitory markers. Collectively, our data suggest that the persistent viral lytic gene expression during latency is the cause of the chronic inflammatory response leading to the exhaustion of the resident T cells in the EP. PMID- 27357151 TI - CD8+ Effector T Cell Migration to Pancreatic Islet Grafts Is Dependent on Cognate Antigen Presentation by Donor Graft Cells. AB - Pancreatic islet transplantation is a promising therapy for diabetes, but acute rejection of the islets by host effector T cells has hindered clinical application. In this study, we addressed the mechanisms of CD8(+) effector T cell migration to islet grafts because interrupting this step is key to preventing rejection. We found that effector T cell migration to revascularized islet transplants in mice is dependent on non-self Ag recognition rather than signaling via Galphai-coupled chemokine receptors. Presentation of non-self Ag by donor cells was necessary for migration, whereas Ag presentation by recipient cells was dispensable. We also observed that deficiency of SKAP1, an immune cell adaptor downstream of the TCR and important for integrin activation, prolongs allograft survival but does not reduce effector T cell migration to the graft. Therefore, effector T cell migration to transplanted islets is Ag driven, not chemokine driven, but SKAP1 does not play a critical role in this process. PMID- 27357150 TI - Network Analysis Identifies Proinflammatory Plasma Cell Polarization for Secretion of ISG15 in Human Autoimmunity. AB - Plasma cells (PCs) as effectors of humoral immunity produce Igs to match pathogenic insult. Emerging data suggest more diverse roles exist for PCs as regulators of immune and inflammatory responses via secretion of factors other than Igs. The extent to which such responses are preprogrammed in B-lineage cells or can be induced in PCs by the microenvironment is unknown. In this study, we dissect the impact of IFNs on the regulatory networks of human PCs. We show that core PC programs are unaffected, whereas PCs respond to IFNs with distinctive transcriptional responses. The IFN-stimulated gene 15 (ISG15) system emerges as a major transcriptional output induced in a sustained fashion by IFN-alpha in PCs and linked both to intracellular conjugation and ISG15 secretion. This leads to the identification of ISG15-secreting plasmablasts/PCs in patients with active systemic lupus erythematosus. Thus, ISG15-secreting PCs represent a distinct proinflammatory PC subset providing an Ig-independent mechanism of PC action in human autoimmunity. PMID- 27357153 TI - NK Cell Activation in the Antitumor Response Induced by IFN-alpha Dendritic Cells Loaded with Apoptotic Cells from Follicular Lymphoma Patients. AB - Follicular lymphoma (FL) is the most common form of indolent non-Hodgkin lymphoma. This malignancy is considered virtually incurable, with high response rates to therapy but frequent relapses. We investigated the ability of monocyte derived dendritic cells generated in the presence of IFN-alpha and GM-CSF (IFN DC) and loaded with apoptotic lymphoma cells to activate immune responses against FL cells, with the ultimate goal of designing novel patient-specific vaccination strategies for the treatment of FL. In this article, we show that apoptotic tumor cell-loaded IFN-DC from FL patients, which were cultured for 2 wk with autologous lymphocytes, led to Th1 response skewing, based on significantly higher levels of IFN-gamma production and a remarkable increase in CD8(+) and NK cell frequency, consistent with the detection of enhanced cytotoxic effector function toward autologous FL cells. IFN-DC were found to promote efficient NK cell activation, increased expression of cytotoxicity receptors, and extensive IFN-gamma production in the virtual absence of IL-10. Moreover, direct recognition and killing of primary autologous lymphoma cells by activated NK cells from FL patients was also demonstrated. A critical role was demonstrated for MHC class I related chain A and B and membrane-bound IL-15 in IFN-DC-mediated NK cell activation and early IFN-gamma production. The overall results indicate that IFN DC loaded with autologous apoptotic FL cells represent a valuable tool for improving the potency of therapeutic cancer vaccines through the efficient induction of NK cell activation and promotion of CD8(+) T cell antitumor immunity. PMID- 27357152 TI - Distinct CD55 Isoform Synthesis and Inhibition of Complement-Dependent Cytolysis by Hepatitis C Virus. AB - CD55/DAF, one of the regulators of complement activation, is known to limit excess complement activation on the host cell surface by accelerating the decay of C3 convertase. We reported previously that hepatitis C virus (HCV) infection or virus core protein expression upregulates CD55 expression. CD55 associates with HCV particles, potentially protecting HCV from lysis in circulation. An increase in CD55 on the surface of HCV-infected cells may inhibit complement mediated cell killing. In this study, we show that Abs against cancer cell surface proteins induce complement-dependent cytolysis or Ab-dependent cell mediated cytotoxicity of immortalized human hepatocytes in the presence of CD55 blocking Ab. CD55 has a secreted isoform (sCD55) that is generated by alternative splicing. We observed that sCD55 is induced in HCV-infected or HCV replicon harboring cells, as well as in liver biopsy samples from chronically HCV-infected patients. Conditioned medium from HCV-infected hepatoma cells (Huh7.5 cells) or immortalized human hepatocytes inhibited C3 convertase activity and complement dependent cytolysis of sheep blood erythrocytes. Chronically HCV-infected patient sera inhibited C3 convertase activity, further implicating HCV-specific impairment of complement function in infected humans. CD55-blocking Ab inhibited erythrocyte lysis by conditioned medium, suggesting that CD55/sCD55 impairs convertase activity. Together, our data show that HCV infection induces sCD55 expression in HCV-infected cell culture-conditioned medium and inhibits C3 convertase activity. This may have implications for modulating complement mediated immune function in the microenvironment and on HCV-harboring cells. PMID- 27357154 TI - ZBTB32 Restricts the Duration of Memory B Cell Recall Responses. AB - Memory B cell responses are more rapid and of greater magnitude than are primary Ab responses. The mechanisms by which these secondary responses are eventually attenuated remain unknown. We demonstrate that the transcription factor ZBTB32 limits the rapidity and duration of Ab recall responses. ZBTB32 is highly expressed by mouse and human memory B cells but not by their naive counterparts. Zbtb32(-/-) mice mount normal primary Ab responses to T-dependent Ags. However, Zbtb32(-/-) memory B cell-mediated recall responses occur more rapidly and persist longer than do control responses. Microarray analyses demonstrate that Zbtb32(-/-) secondary bone marrow plasma cells display elevated expression of genes that promote cell cycle progression and mitochondrial function relative to wild-type controls. BrdU labeling and adoptive transfer experiments confirm more rapid production and a cell-intrinsic survival advantage of Zbtb32(-/-) secondary plasma cells relative to wild-type counterparts. ZBTB32 is therefore a novel negative regulator of Ab recall responses. PMID- 27357156 TI - No Evidence of Dengue Virus Infections in Several Species of Bats Captured in Central and Southern Mexico. AB - Bats are reservoirs for viruses with zoonotic potential in the Americas, and scattered evidence exists suggesting that bats may act as reservoirs for dengue virus (DENV). To explore further the role of bats as part of DENV sylvatic cycles, 240 bats of 18 species were captured in 2 states of Mexico with contrasting ecological characteristics but concurrent DENV activity in humans. RT PCR analysis of RNA extracted from liver or spleen tissue from de bats failed to show evidence for the presence of DENV nucleic acids in these organs. In addition, plasma assayed by plaque reduction neutralization test showed no evidence of neutralizing anti-DENV antibodies. These results suggest that American bats may not be reservoirs or amplification host for DENV infection. PMID- 27357157 TI - Safety and efficacy of flow re-direction endoluminal device (FRED) in the treatment of cerebral aneurysms: a single center experience. AB - BACKGROUND: Experience with the endovascular treatment of cerebral aneurysms by the Flow Re-Direction Endoluminal Device (FRED) is still limited. The aim of this study is to discuss the results and complications of this new flow diverter device (FDD). METHODS: Between November 2013 and April 2015, 20 patients (15 female and five male) harboring 24 cerebral aneurysms were treated with FRED FDD in a single center. RESULTS: Complete occlusion was obtained in 20/24 aneurysms (83 %) and partial occlusion in four (17 %). Intraprocedural technical complication occurred in one case (4 %) and post-procedural complications in three (12 %). None reported neurological deficits (mRS = 0). All FRED were patent at follow-up. No early or delayed aneurysm rupture, no subarachnoid (SAH) or intraparenchymal hemorrhage (IPH) no ischemic complications and no deaths occurred. CONCLUSIONS: Endovascular treatment with FRED FDD is a safe treatment for unruptured cerebral aneurysms, resulting in a high rate of occlusion. The FRED is substantially equivalent to the other known FDDs, which show similar functions and technical profiles. PMID- 27357155 TI - Neonatal Bacillus Calmette-Guerin vaccination alleviates lipopolysaccharide induced neurobehavioral impairments and neuroinflammation in adult mice. AB - The Bacillus Calmette-Guerin (BCG) vaccine is routinely administered to human neonates worldwide. BCG has recently been identified as a neuroprotective immune mediator in several neuropathological conditions, exerting neuroprotection in a mouse model of Parkinson's disease and slowing the progression of clinically isolated syndrome in patients with multiple sclerosis. The immune system is significantly involved in brain development, and several types of neonatal immune activations exert influences on the brain and behavior following a secondary immune challenge in adulthood. However, whether the neonatal BCG vaccination affects the brain in adulthood remains to be elucidated. In the present study, newborn C57BL/6 mice were injected subcutaneously with BCG (105 colony forming units) or phosphate-buffered saline (PBS). A total of 12 weeks later, the mice were injected intraperitoneally with 330 ug/kg lipopolysaccharide (LPS) or PBS. The present study reported that the neonatal BCG vaccination alleviated sickness, anxiety and depression-like behavior, lessened the impairments in hippocampal cell proliferation and downregulated the proinflammatory responses in the serum and brain that were induced by the adult LPS challenge. However, BCG vaccination alone had no evident influence on the brain and behavior in adulthood. In conclusion, the neonatal BCG vaccination alleviated the neurobehavioral impairments and neuroinflammation induced by LPS exposure in adult mice, suggesting a potential neuroprotective role of the neonatal BCG vaccination in adulthood. PMID- 27357158 TI - Hydrothermal synthesis for high-quality glutathione-capped Cdx Zn1 - x Se and Cdx Zn1 - x Se/ZnS alloyed quantum dots and its application in Hg(II) sensing. AB - High-quality Cdx Zn1 - x Se and Cdx Zn1 - x Se/ZnS core/shell quantum dots (QDs) emitting in the violet-green spectral range have been successfully prepared using hydrothermal methods. The obtained aqueous Cdx Zn1 - x Se and Cdx Zn1 - x Se/ZnS QDs exhibit a tunable photoluminescence (PL) emission (from 433.5 nm to 501.2 nm) and a favorable narrow photoluminescence bandwidth [full width at half maximum (FWHM): 30-42 nm]. After coating with a ZnS shell, the quantum yield increases from 40.2% to 48.1%. These Cdx Zn1 - x Se and Cdx Zn1 - x Se/ZnS QDs were characterized by transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Fourier transform infrared (FTIR) spectroscopy. To further understand the alloying mechanism, the growth kinetics of Cdx Zn1 - x Se were investigated through measuring the fluorescence spectra and X-ray diffraction spectra at different growth intervals. The results demonstrate that the inverted ZnSe/CdSe core/shell structure is formed initially after the injection of Cd2+ . With further heating, the core/shell structured ZnSe/CdSe is transformed into alloyed Cdx Zn1 - x Se QDs with the diffusion of Cd2+ into ZnSe matrices. With increasing the reaction temperature from 100 degrees C to 180 degrees C, the duration time of the alloying process decreases from 210 min to 20 min. In addition, the cytotoxicity of Cdx Zn1 - x Se and Cdx Zn1 - x Se/ZnS QDs were investigated. The results indicate that the as-prepared Cdx Zn1 - x Se/ZnS QDs have low cytotoxicity, which makes them a promising probe for cell imaging. Finally, the as-prepared Cdx Zn1 - x Se/ZnS QDs were utilized to ultrasensitively and selectively detect Hg2+ ions with a low detection limit (1.8 nM). PMID- 27357159 TI - Vasoconstrictor eicosanoids and impaired microvascular function in inactive and insulin-resistant primates. AB - The inability to augment capillary blood volume (CBV) in response to insulin or glucose is thought to contribute to insulin resistance (IR) by limiting glucose uptake in key storage sites. Understanding the mechanisms that contribute to impaired CBV augmentation early in the onset of IR may lead to new future therapies. We hypothesized that inactivity alters the balance of vasoactive eicosanoids and contributes to microvascular IR. In ten activity-restricted (AR) and six normal activity adult male rhesus macaques, contrast-enhanced ultrasound of skeletal muscle blood flow and CBV was performed at baseline and during intravenous glucose tolerance test (IVGTT). Plasma was analyzed for vasoconstrictor hydroxyeicosatetraenoic acids (HETEs) and the ratio of vasodilatory epoxyeicosatrienoic acids (EETs) to their less biologically active dihydroxyeicosatrienoic acids (DHETs) as an indirect measure of soluble epoxide hydrolase activity. AR primates were IR during IVGTT and had a 45% lower glucose stimulated CBV response. Vasoconstrictor 18-HETE and 19-HETE and the DHET/EET ratio were markedly elevated in the AR group and correlated inversely with the CBV response. In addition, levels of 18-HETE and 19-HETE correlated directly with microvascular IR. We conclude that a shift toward increased eicosanoid vasoconstrictor tone correlates with abnormal skeletal muscle vascular recruitment and may contribute to IR. PMID- 27357160 TI - Fungal Associates of the Xylosandrus compactus (Coleoptera: Curculionidae, Scolytinae) Are Spatially Segregated on the Insect Body. AB - Studies of symbioses have traditionally focused on explaining one-to-one interactions between organisms. In reality, symbioses are often much more dynamic. They can involve many interacting members, and change depending on context. In studies of the ambrosia symbiosis-the mutualism between wood borer beetles and fungi-two variables have introduced uncertainty when explaining interactions: imprecise symbiont identification, and disregard for anatomical complexity of the insects. The black twig borer, Xylosandrus compactus Eichhoff, is a globally invasive ambrosia beetle that infests >200 plant species. Despite many studies on this beetle, reports of its primary symbionts are conflicting. We sampled adult X. compactus and infested plant material in central Florida to characterize the fungal symbiont community using dilution series, beetle partitioning, and DNA-based identification. X. compactus was consistently associated with two fungal taxa, Fusarium spp. and Ambrosiella xylebori Multivariate analyses revealed that A. xylebori was strongly associated with the beetle mycangium while Fusarium spp. were associated with the abdomen and external surfaces. The Fusarium spp. carried by X. compactus are not members of the Ambrosia Fusarium Clade, and are probably not mutualists. Fungal community composition of the mycangium was less variable than external body surfaces, thus providing a more consistent fungal inoculum. This is the first report of spatial partitioning as a mechanism for maintenance of a multimember ambrosia fungus community. Our results provide an explanation for discrepancies among previous reports, and suggest that conflicting results are not due to differences in symbiont communities, but due to inconsistent and incomplete sampling. PMID- 27357161 TI - Selective Foraging by Pogonomyrmex salinus (Hymenoptera: Formicidae) in Semiarid Grassland: Implications for a Rare Plant. AB - Selective foraging by granivores can have important consequences for the structure and composition of plant communities, and potentially severe consequences for rare plant species. To understand how granivore foraging behavior affects common and rare plant species, diet selection should be viewed relative to the availability of alternative seed options, and with consideration of the individual attributes of those seeds (e.g., morphology, nutrient content). We examined the foraging decisions of Owyhee harvester ants, Pogonomyrmex salinus (Olsen), in semiarid grassland dominated by two species of grass, Poa secunda and Bromus tectorum, and two species of mustard, Sisymbrium altissimum and Lepidium papilliferum The latter is a rare plant endemic to southwestern Idaho, and its seeds are readily consumed by P. salinus We examined the diets of P. salinus colonies in June and July over three years and compared these values to the weekly availability of seeds on the ground in a 3-12 -m radius around individual ant colonies. Small-seeded species (P. secunda, S. altissimum, and L. papilliferum) were usually overrepresented in the diet of ants relative to their availability, whereas the large seeds of B. tectorum were largely avoided despite being abundant and nutritious. The reduced travel time associated with carrying small seeds may overshadow differences in nutritional content among seed types, except in times when small seeds are in short supply. Lepidium papilliferum appears particularly vulnerable to seed predation, likely in part because it grows in dense patches that are easily exploited by foragers. PMID- 27357162 TI - Arthropod Pests and Predators Associated With Bittersweet Nightshade, a Noncrop Host of the Potato Psyllid (Hemiptera: Triozidae). AB - Bittersweet nightshade (Solanum dulcamara L.) is a key noncrop host of the potato psyllid (Bactericera cockerelli Sulc), proposed to be a source of the psyllids that colonize potato (Solanum tuberosum L.) fields in the northwestern United States. Here, we describe the broader community of arthropod potato pests, and also predatory arthropods, found in bittersweet nightshade patches. Over 2 yr, we sampled arthropods in patches of this weed spanning the potato-growing region of eastern Washington State. The potato psyllid was the most abundant potato pest that we found, with reproduction of these herbivores recorded throughout much of the growing season where this was measured. Aphid, beetle, and thrips pests of potato also were collected on bittersweet nightshade. In addition to these herbivores, we found a diverse community of >40 predatory arthropod taxa. Spiders, primarily in the Families Dictynidae and Philodromidae, made up 70% of all generalist predator individuals collected. Other generalist predators included multiple species of predatory mites, bugs, and beetles. The coccinellid beetle Stethorus punctillum (Weise) was observed eating psyllid eggs, while the parasitoid wasp Tamarixia triozae (Burks) was observed parasitizing potato psyllid nymphs. Overall, our survey verified the role of bittersweet nightshade as a potato psyllid host, while suggesting that other potato pests also use these plants. At the same time, we found that bittersweet nightshade patches were associated with species-rich communities of natural enemies. Additional work is needed to directly demonstrate movement of pests, and perhaps also predators, from bittersweet nightshade to potato fields. PMID- 27357163 TI - Too many covariates and too few cases? - a comparative study. AB - Prior research indicates that 10-15 cases or controls, whichever fewer, are required per parameter to reliably estimate regression coefficients in multivariable logistic regression models. This condition may be difficult to meet even in a well-designed study when the number of potential confounders is large, the outcome is rare, and/or interactions are of interest. Various propensity score approaches have been implemented when the exposure is binary. Recent work on shrinkage approaches like lasso were motivated by the critical need to develop methods for the p >> n situation, where p is the number of parameters and n is the sample size. Those methods, however, have been less frequently used when p~n, and in this situation, there is no guidance on choosing among regular logistic regression models, propensity score methods, and shrinkage approaches. To fill this gap, we conducted extensive simulations mimicking our motivating clinical data, estimating vaccine effectiveness for preventing influenza hospitalizations in the 2011-2012 influenza season. Ridge regression and penalized logistic regression models that penalize all but the coefficient of the exposure may be considered in these types of studies. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27357164 TI - Assessment of the internal structure of Computer-based Assessment of Memory and Cognitive Impairment. PMID- 27357165 TI - A New Strategy for Humidity Independent Oxide Chemiresistors: Dynamic Self Refreshing of In2 O3 Sensing Surface Assisted by Layer-by-Layer Coated CeO2 Nanoclusters. AB - The humidity dependence of the gas sensing characteristics of metal oxide semiconductors has been one of the greatest obstacles for gas sensor applications during the last five decades because ambient humidity dynamically changes with the environmental conditions. Herein, a new and novel strategy is reported to eliminate the humidity dependence of the gas sensing characteristics of oxide chemiresistors via dynamic self-refreshing of the sensing surface affected by water vapor chemisorption. The sensor resistance and gas response of pure In2 O3 hollow spheres significantly change and deteriorate in humid atmospheres. In contrast, the humidity dependence becomes negligible when an optimal concentration of CeO2 nanoclusters is uniformly loaded onto In2 O3 hollow spheres via layer-by-layer (LBL) assembly. Moreover, In2 O3 sensors LBL-coated with CeO2 nanoclusters show fast response/recovery, low detection limit (500 ppb), and high selectivity to acetone even in highly humid conditions (relative humidity 80%). The mechanism underlying the dynamic refreshing of the In2 O3 sensing surfaces regardless of humidity variation is investigated in relation to the role of CeO2 and the chemical interaction among CeO2 , In2 O3 , and water vapor. This strategy can be widely used to design high performance gas sensors including disease diagnosis via breath analysis and pollutant monitoring. PMID- 27357167 TI - Long-term safety of replication-defective smallpox vaccine (MVA-BN) in atopic eczema and allergic rhinitis. AB - BACKGROUND: Availability of a safe smallpox vaccine may be necessary under certain circumstances. Use of the old life virus vaccine was associated with serious adverse events, particularly in the setting of atopic eczema (AE) and immunodeficiency. Modified virus Ankara (MVA)-BN, a highly attenuated strain of vaccinia virus, was developed for vaccination with improved safety profile. METHODS: A phase 1 study was conducted in 60 subjects without history of smallpox vaccination to gain experience with smallpox vaccination using this strain in healthy and atopic subjects. Healthy subjects, subjects with a history of AE, subjects with mild active AE and subjects with mild allergic rhinitis without AE were equally allocated into four groups. MVA-BN was injected s.c. in a dose of 108 TCID50 twice in a 4-week interval. RESULTS: No serious or unexpected adverse reactions were reported. All subjects experienced mild to moderate pain and redness at the injection site. Dermatologic examinations did not reveal any unfavourable reactions to the study medication, particularly no sign or exacerbation of eczema for as long as 196 days. All subjects seroconverted after two vaccinations and no significant difference in antibody titres between the four different groups was observed. CONCLUSIONS: A good safety profile of the MVA BN vaccine was shown. The absence of adverse events in subjects with atopic disorders appears promising for the development of a safe smallpox vaccine for patients with AE or other atopic diseases. PMID- 27357166 TI - Xanthine oxidoreductase mediates membrane docking of milk-fat droplets but is not essential for apocrine lipid secretion. AB - KEY POINTS: Xanthine oxidoreductase (XOR) modulates milk lipid secretion and lactation initiation. XOR is required for butyrophilin1a1 clustering in the membrane during milk lipid secretion. XOR mediates apical membrane reorganization during milk lipid secretion. Loss of XOR delays milk fat globule secretion. XOR loss alters the proteome of milk fat globules. ABSTRACT: Apocrine secretion is utilized by epithelial cells of exocrine glands. These cells bud off membrane bound particles into the lumen of the gland, losing a portion of the cytoplasm in the secretion product. The lactating mammary gland secretes milk lipid by this mechanism, and xanthine oxidoreductase (XOR) has long been thought to be functionally important. We generated mammary-specific XOR knockout (MGKO) mice, expecting lactation to fail. Histology of the knockout glands showed very large lipid droplets enclosed in the mammary alveolar cells, but milk analysis showed that these large globules were secreted. Butyrophilin, a membrane protein known to bind to XOR, was clustered at the point of contact of the cytoplasmic lipid droplet with the apical plasma membrane, in the wild-type gland but not in the knockout, suggesting that XOR mediates 'docking' to this membrane. Secreted milk fat globules were isolated from mouse milk of wild-type and XOR MGKO dams, and subjected to LC-MS/MS for analysis of protein component. Proteomic results showed that loss of XOR leads to an increase in cytoplasmic, cytoskeletal, Golgi apparatus and lipid metabolism proteins associated with the secreted milk fat globule. Association of XOR with the lipid droplet results in membrane docking and more efficient retention of cytoplasmic components by the secretory cell. Loss of XOR then results in a reversion to a more rudimentary, less efficient, apocrine secretion mechanism, but does not prevent milk fat globule secretion. PMID- 27357168 TI - Targeted Transcriptional Profiling of Microdissected Biopsy Specimens Representing Early Colonic Neoplasia. AB - Our incomplete understanding of the critical changes that accompany the earliest stages of tumor initiation provides a substantial hurdle for the development of novel intervention strategies for cancer prevention. Premalignant lesions are inherently difficult to characterize given their diminutive size, creating technical obstacles for accurate genetic profiling. Here, we describe an approach combining laser-capture microdissection (LCM) with targeted RNA-sequencing to study the transcriptional state of epithelial and stromal cells during the earliest detectable stage of human colorectal neoplasia, the aberrant crypt foci (ACF). We provide a robust and reproducible workflow for RNA isolation, library preparation, and expression profiling of laser-captured cells from frozen OCT embedded tissue specimens. It is anticipated that the methodological approach outlined in this report will provide a framework for a broad range of microgenomics analyses that can be routinely applied to many other premalignant tissues. J. Cell. Biochem. 117: 2677-2681, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27357169 TI - Local versus global biological network alignment. AB - MOTIVATION: Network alignment (NA) aims to find regions of similarities between species' molecular networks. There exist two NA categories: local (LNA) and global (GNA). LNA finds small highly conserved network regions and produces a many-to-many node mapping. GNA finds large conserved regions and produces a one to-one node mapping. Given the different outputs of LNA and GNA, when a new NA method is proposed, it is compared against existing methods from the same category. However, both NA categories have the same goal: to allow for transferring functional knowledge from well- to poorly-studied species between conserved network regions. So, which one to choose, LNA or GNA? To answer this, we introduce the first systematic evaluation of the two NA categories. RESULTS: We introduce new measures of alignment quality that allow for fair comparison of the different LNA and GNA outputs, as such measures do not exist. We provide user friendly software for efficient alignment evaluation that implements the new and existing measures. We evaluate prominent LNA and GNA methods on synthetic and real-world biological networks. We study the effect on alignment quality of using different interaction types and confidence levels. We find that the superiority of one NA category over the other is context-dependent. Further, when we contrast LNA and GNA in the application of learning novel protein functional knowledge, the two produce very different predictions, indicating their complementarity. Our results and software provide guidelines for future NA method development and evaluation. AVAILABILITY AND IMPLEMENTATION: Software: http://www.nd.edu/~cone/LNA_GNA CONTACT: : tmilenko@nd.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27357170 TI - Network-based pathway enrichment analysis with incomplete network information. AB - MOTIVATION: Pathway enrichment analysis has become a key tool for biomedical researchers to gain insight into the underlying biology of differentially expressed genes, proteins and metabolites. It reduces complexity and provides a system-level view of changes in cellular activity in response to treatments and/or in disease states. Methods that use existing pathway network information have been shown to outperform simpler methods that only take into account pathway membership. However, despite significant progress in understanding the association amongst members of biological pathways, and expansion of data bases containing information about interactions of biomolecules, the existing network information may be incomplete or inaccurate and is not cell-type or disease condition-specific. RESULTS: We propose a constrained network estimation framework that combines network estimation based on cell- and condition-specific high-dimensional Omics data with interaction information from existing data bases. The resulting pathway topology information is subsequently used to provide a framework for simultaneous testing of differences in expression levels of pathway members, as well as their interactions. We study the asymptotic properties of the proposed network estimator and the test for pathway enrichment, and investigate its small sample performance in simulated and real data settings. AVAILABILITY AND IMPLEMENTATION: The proposed method has been implemented in the R-package netgsa available on CRAN. CONTACT: jinma@upenn.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27357171 TI - Estimating and testing high-dimensional mediation effects in epigenetic studies. AB - MOTIVATION: High-dimensional DNA methylation markers may mediate pathways linking environmental exposures with health outcomes. However, there is a lack of analytical methods to identify significant mediators for high-dimensional mediation analysis. RESULTS: Based on sure independent screening and minimax concave penalty techniques, we use a joint significance test for mediation effect. We demonstrate its practical performance using Monte Carlo simulation studies and apply this method to investigate the extent to which DNA methylation markers mediate the causal pathway from smoking to reduced lung function in the Normative Aging Study. We identify 2 CpGs with significant mediation effects. AVAILABILITY AND IMPLEMENTATION: R package, source code, and simulation study are available at https://github.com/YinanZheng/HIMA CONTACT: lei.liu@northwestern.edu. PMID- 27357172 TI - Accounting for pairwise distance restraints in FFT-based protein-protein docking. AB - : ClusPro is a heavily used protein-protein docking server based on the fast Fourier transform (FFT) correlation approach. While FFT enables global docking, accounting for pairwise distance restraints using penalty terms in the scoring function is computationally expensive. We use a different approach and directly select low energy solutions that also satisfy the given restraints. As expected, accounting for restraints generally improves the rank of near native predictions, while retaining or even improving the numerical efficiency of FFT based docking. AVAILABILITY AND IMPLEMENTATION: The software is freely available as part of the ClusPro web-based server at http://cluspro.org/nousername.php CONTACT: midas@laufercenter.org or vajda@bu.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27357173 TI - Long-Term Safety of Dapagliflozin in Older Patients with Type 2 Diabetes Mellitus: A Pooled Analysis of Phase IIb/III Studies. AB - OBJECTIVE: To evaluate the 104-week safety of dapagliflozin in older patients with type 2 diabetes mellitus. METHODS: Pooled analysis assessing general safety (nine phase III studies <=104 weeks) and cardiovascular safety (21 phase IIb/III studies <=208 weeks) by age (<65; >=65; >=75 years). Patients with type 2 diabetes mellitus (+/-background glucose-lowering therapy) received: dapagliflozin 10 mg (n = 2026) vs. placebo (n = 1956) (nine-study pool); or dapagliflozin (2.5-50 mg; n = 5936) vs. control (placebo/comparator) (n = 3403) (21-study pool). RESULTS: Adverse events (AEs) and discontinuations owing to AEs were more common in older vs. younger patients, and were more frequent with dapagliflozin than placebo (AEs: <65 years: 73.1 vs. 70.7 %; >=65 years: 77.4 vs. 73.1 %; >=75 years: 80.4 vs. 75.3 %, respectively; discontinuations: <65 years: 5.9 vs. 5.0 %; >=65 years: 14.4 vs. 12.2 %; >=75 years: 26.8 vs. 22.1 %, respectively); serious AE (SAE) frequency was similar (<65 years: 11.0 vs. 11.8 %; >=65 years: 20.0 vs. 20.2 %; >=75 years: 19.6 vs. 18.2 %, respectively). Hypoglycaemia frequency was similar across age groups and was higher with dapagliflozin than placebo (<65 years: 18.0 vs. 13.4 %; >=65 years: 20.2 vs. 17.7 %; >=75 years: 17.5 vs. 16.9 %, respectively); major episodes were rare. Urinary tract infection frequency was similar between treatment groups in older patients, with no increase vs. younger patients (<65 years: 8.8 vs. 5.5 %; >=65 years: 8.1 vs. 7.6 %; >=75 years: 8.2 vs. 9.1 %, respectively); urinary tract infection SAEs were rare. Genital infection AEs were more common with dapagliflozin, with no increase in older patients (<65 years: 8.2 vs. 1.0 %; >=65 years: 6.6 vs. 0.9 %; >=75 years: 7.2 vs. 0.0 %, respectively) and no SAEs. Volume reduction AEs were uncommon, with a higher frequency with dapagliflozin vs. placebo and in patients >=75 years (<65 years: 1.7 vs. 1.2 %; >=65 years: 2.3 vs. 1.7 %; >=75 years: 3.1 vs. 2.6 %, respectively). Dapagliflozin did not increase the risk of fractures (<65 years: 1.1 vs. 1.1 %; >=65 years: 1.1 vs. 2.7 %; >=75 years: 1.0 vs. 2.6 %, respectively) or falls (<65 years: 0.7 vs. 0.7 %; >=65 years: 0.6 vs. 2.1 %; >=75 years: 0.0 vs. 1.3 %, respectively), regardless of age. AEs of renal function were more common with dapagliflozin than placebo and increased with age (<65 years: 3.5 vs. 2.3 %; >=65 years: 14.0 vs. 7.9 %; >=75 years: 29.9 vs. 20.8 %, respectively). Most were non-serious small transient increases in serum creatinine. Dapagliflozin did not increase cardiovascular risk regardless of age [hazard ratio (95 % confidence interval) vs. CONTROL: <65 years: 0.726 (0.473, 1.114); >=65 years: 0.879 (0.565, 1.366); >=75 years: 0.950 (0.345, 2.617), respectively]. CONCLUSION: Dapagliflozin treatment up to 104 weeks was well tolerated in older patients. Older dapagliflozin-treated patients had more renal AEs than placebo-treated patients; the majority of which were non-serious small transient changes in serum creatinine. PMID- 27357174 TI - Curative treatment of head and neck squamous cell carcinoma : Organ preservation strategies in clinical routine in German-speaking countries. AB - INTRODUCTION: For the treatment of head and neck squamous cell carcinoma (HNSCC), there are currently no official standard of care guidelines in German-speaking countries, with the exception of oral cavity cancer. In order to learn about the applied treatment modalities in the clinical routine, we conducted a web-based survey to evaluate the local standards of palliative and curative treatment of HNSCC. This article focuses on the curative treatment options and organ preservation strategies. MATERIALS AND METHODS: The survey consisted of a web based questionnaire that was performed between November 2013 and July 2014. The questionnaire included ten multiple-choice questions and four open questions in the section about curative treatment. RESULTS: Altogether, 62 of the 204 addressed centers participated in the survey. For primary chemoradiation (CRT), most centers used a platinum-based chemotherapy (52/54, 96.3 %). Induction chemotherapy (ICT) was offered in 37 of the 62 centers (60 %). In oral cavity cancer, CRT and ICT were used in 37.5 and 4.3 % of the cases, respectively. In oropharyngeal cancer, CRT and ICT were applied in 44.5 and 10.3 % of cases, respectively. For hypopharyngeal cancer, 44.8 % of the patients received CRT and 11.8 % received ICT, while for laryngeal cancer 35.9 % received CRT and 9.4 % underwent ICT. CONCLUSION: Our data showed that a variety of treatments are used for HNSCC within German-speaking countries. Many centers offer ICT. The majority of the hospitals uses platinum-based therapy as a conservative first-line option in their organ preservation protocols. PMID- 27357175 TI - Bone Mineral Density Is Positively Related to Carotid Intima-Media Thickness: Findings From a Population-Based Study in Adolescents and Premenopausal Women. AB - Osteoporosis and cardiovascular disease (CVD) are both common causes of morbidity and mortality. Previous studies, mainly of people older than 60 years, suggest a relationship between these conditions. Our aim was to determine the association between bone characteristics and CVD markers in younger and middle-aged individuals. Women (n = 3366) and their adolescent offspring (n = 4368) from the UK population-based cohort study, Avon Longitudinal Study of Parents and Children (ALSPAC), were investigated. We measured total body (TB) and hip bone mineral density (BMD), TB bone area (BA) and bone mineral content (BMC) by dual-energy X ray absorptiometry (DXA), and carotid intima-media thickness (cIMT) by high resolution ultrasound. Arterial distensibility was calculated as the difference between systolic and diastolic arterial diameters. Linear regression determined associations between bone exposures and cIMT (in adolescents) and both cIMT and arterial distensibility (in women), generating partial correlation coefficients. Mean (SD) age of women was 48 (4.2) years, body mass index (BMI) was 26.2 (5.0) kg/m2 , and 71% were premenopausal. In confounder-adjusted analyses (age, height, lean mass, fat mass, menopause, smoking, estrogen replacement, calcium/vitamin D supplementation, and education) TB and hip BMD were both positively associated with cIMT (0.071 [0.030, 0.112], p = 0.001; 0.063 [0.025, 0.101], p = 0.001, respectively). Femoral neck BMD and TB BMD, BMC, and BA were positively associated with arterial distensibility. Mean (SD) age of adolescents was 17 (0.4) years, BMI was 23 (4.1) kg/m2 , and 44.5% were male. Total hip and TB measurements were positively associated with cIMT, with similar magnitudes of association to those found in their mothers. In contrast to most published findings, we identified weak positive associations between BMD and cIMT in predominantly premenopausal women and their adolescent offspring. We found greater femoral neck BMD and TB DXA measurements to be associated with reduced arterial stiffness. Rather than a relationship with preclinical atherosclerosis, in these relatively young populations, we speculate our associations between BMD, cIMT, and arterial distensibility may reflect a shared relationship between bone and vascular growth and development. (c) 2016 American Society for Bone and Mineral Research. PMID- 27357176 TI - Life in leaf litter: novel insights into community dynamics of bacteria and fungi during litter decomposition. AB - Microorganisms play a crucial role in the biological decomposition of plant litter in terrestrial ecosystems. Due to the permanently changing litter quality during decomposition, studies of both fungi and bacteria at a fine taxonomic resolution are required during the whole process. Here we investigated microbial community succession in decomposing leaf litter of temperate beech forest using pyrotag sequencing of the bacterial 16S and the fungal internal transcribed spacer (ITS) rRNA genes. Our results reveal that both communities underwent rapid changes. Proteobacteria, Actinobacteria and Bacteroidetes dominated over the entire study period, but their taxonomic composition and abundances changed markedly among sampling dates. The fungal community also changed dynamically as decomposition progressed, with ascomycete fungi being increasingly replaced by basidiomycetes. We found a consistent and highly significant correlation between bacterial richness and fungal richness (R = 0.76, P < 0.001) and community structure (RM antel = 0.85, P < 0.001), providing evidence of coupled dynamics in the fungal and bacterial communities. A network analysis highlighted nonrandom co-occurrences among bacterial and fungal taxa as well as a shift in the cross kingdom co-occurrence pattern of their communities from the early to the later stages of decomposition. During this process, macronutrients, micronutrients, C:N ratio and pH were significantly correlated with the fungal and bacterial communities, while bacterial richness positively correlated with three hydrolytic enzymes important for C, N and P acquisition. Overall, we provide evidence that the complex litter decay is the result of a dynamic cross-kingdom functional succession. PMID- 27357177 TI - Outcomes After Oncoplastic Breast-Conserving Surgery in Breast Cancer Patients: A Systematic Literature Review. AB - BACKGROUND: Surgeons have increasingly performed breast-conserving surgery (BCS) utilizing oncoplastic techniques in place of standard lumpectomy for early-stage breast cancer. We assess oncologic outcomes after oncoplastic BCS for T1-T2 breast cancer. METHODS: A systematic literature review identified peer-reviewed articles in PubMed evaluating BCS with oncoplastic reconstruction. Selected studies reported on positive margin rate (PMR), re-excision rate (RR), conversion to mastectomy rate (CMR), overall survival (OS), disease-free survival (DFS), local recurrence (LR), distant recurrence (DR), complication rate, and/or cosmetic outcomes. RESULTS: The search yielded 474 articles; 55 met the inclusion criteria and collectively evaluated 6011 patients with a mean age 54.6 years over a mean follow-up 50.5 months. T1 (43.8 %) and T2 (39.3 %) invasive ductal carcinoma were the most common tumor histopathologies. PMR, RR, and CMR were 10.8, 6.0, and 6.2 %, respectively, while OS, DFS, LR and DR were 95.0, 90.0, 3.2, and 8.7 %, respectively. Margin widths were heterogeneously defined in studies that included margin assessment. The PMR was not significantly different when positive margins were defined as tumor <10, <5, < 2, and <1 mm from ink margin, or tumor on ink (p = 0.162). Eleven studies reported specific margins for 1455 patients, of whom 143 (9.8 %) had positive margins, including 113 (7.8 %) with tumor on ink. CONCLUSIONS: This study is the largest comprehensive literature review to date on oncoplastic BCS. Our systematic review reveals high rates of OS and DFS with low LR, DR, PMR, RR, CMR and complication rates, thereby confirming the oncologic safety of this procedure in patients with T1-T2 invasive breast cancer. PMID- 27357178 TI - Different Prognostic Implications of Residual Disease After Neoadjuvant Treatment: Impact of Ki 67 and Site of Response. AB - BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) can be used as an independent prognostic factor in neoadjuvant trials. The objective of this study was to determine the impact of Ki 67 expression and site of response on overall survival (OS) and disease-free survival (DFS) across different molecular subtypes of breast cancer following NAC. METHODS: Records from 357 patients who received NAC from 2004 to 2011 were reviewed. Univariate and multivariate analyses were performed to analyze clinical and pathological factors that influence pCR and DFS. RESULTS: Mean follow-up time was 45 months (range 12-112). pCR was achieved in 82 patients (23 %). According to molecular subtypes, rates of pCR were significantly higher for patients with HER2-positive and triple-negative tumors (69.4 and 32.7 %, respectively; p < 0.001) compared with other molecular subtypes. pCR was a predictive factor of longer OS and DFS. The hazard ratio for DFS in patients with positive lymph nodes (ypN1) after NAC was 2.48 (95 % confidence interval 1.47-4.19). Multivariate analysis showed that molecular subtype, changes in Ki 67 expression, and axillary lymph node response were significantly predictors of OS and DFS. CONCLUSIONS: pCR in the axilla and posttreatment changes in Ki 67 after NAC are associated with improved survival. Depending on axillary staging before NAC, detection of minimal residual disease defined as the presence of isolated tumor cells in the SLN after NAC-may confer different prognosis. Further studies are needed to tailor treatments for patients with residual disease after NAC. PMID- 27357179 TI - Feasibility of Routine Application of Gadoxetic Acid-Enhanced MRI in Combination with Diffusion-Weighted MRI for the Preoperative Evaluation of Colorectal Liver Metastases. AB - BACKGROUND: Gadoxetic acid-enhanced magnetic resonance imaging (MRI) in combination with diffusion-weighted MRI (Gd-EOB-MRI/DWI) has become popular for evaluating colorectal liver metastases (CRLM). This retrospective observational study aimed to determine whether this procedure should be indicated prior to hepatectomy in all patients with CRLM. METHODS: A retrospective survey of relevant data of patients who had undergone hepatectomy for CRLM from 2008 to 2014 was performed. The rates of detection by contrast-enhanced computed tomography (CE-CT) and Gd-EOB-MRI/DWI were evaluated. In addition, relapse-free and overall survivals after primary hepatectomy were compared between patients who had undergone only CE-CT versus those who had undergone both CE-CT and Gd-EOB MRI/DWI. RESULTS: In all, 419 pathologically confirmed CRLM were resected in 202 hepatectomies in 177 patients. The sensitivity of detection of CRLM was 77 % for CE-CT and 93 % for Gd-EOB-MRI/DWI (P < 0.01). The sensitivity of detection of 1 5, 6-10, and 11-15 mm CRLM by CE-CT was 9.6 % (5/52), 47 % (26/55), and 76 % (57/75), respectively, whereas that by Gd-EOB-MRI/DWI was 54 % (28/52), 91 % (50/55), and 99 % (74/75), respectively; these differences are significant (P < 0.01 for all three groups). Relapse-free (P = 0.99) and overall survival (P = 0.79) did not differ significantly between 37 patients evaluated preoperatively by only CE-CT and 168 patients evaluated by both CE-CT and Gd-EOB-MRI/DWI. CONCLUSION: Gd-EOB-MRI/DWI detects small CRLM (<=15 mm) with higher sensitivity than CE-CT. However, whether Gd-EOB-MRI/DWI should be a routine component of preoperative evaluation remains unclear in terms of survival benefit. PMID- 27357180 TI - Current Strategy for the Treatment of Ovarian Germ Cell Tumors: Role of Extensive Surgery. AB - OPINION STATEMENT: The necessity and extent of comprehensive surgical staging (CSS) and lymphadenectomy in the treatment of malignant ovarian germ cell tumors (MOGCTs) is still controversial. However, it is uniformly agreed that CSS with lymphadenectomy is crucial to follow up patients without adjuvant chemotherapy in stage I MOGCTs. Considering the chemotherapy-sensitive nature of MOGCTs, fertility-sparing cytoreductive surgery (FSCS) seems a reasonable approach in initial treatment for patients with advanced stage. When encountered with bilateral MOGCTs, debulking is surely granted if there is no desire for fertility. Both ovaries completely replaced by neoplastic tissue composed the most challenging situation especially when patients require childbearing potential. In dysgerminoma histology, which usually has good prognosis, residual disease could be left to spare fertility. USO of the largest and more heterogeneous ovarian mass and a biopsy of the contralateral lesion may be considered if the patients are compliant to regular follow-up. NACT followed by interval FSCS may be a reasonable option in patients with extensive disease, when initial debulking is not an option or where the poor general condition or clinical findings suggest an increased risk of surgical morbidity or preclude fertility-sparing surgery. This is currently not the standard of care but deserves future study. In some rare situation, when any remaining ovarian tissue means high risk, BSO may be performed with the uterus preserved for possible assisted reproduction with donor egg. Treatment failure occurs in a small group of MOGCTs after primary treatment. A good number of recurrences can be salvaged with selected salvage surgery, especially when optimal secondary cytoreduction can be achieved. Immature teratoma is a subtype of MOGCTs where secondary cytoreduction may have a strong role to play. PMID- 27357182 TI - Anagliptin, A Dipeptidyl Peptidase-4 Inhibitor Ameliorates Arterial Stiffness in Association with Reduction of Remnant-Like Particle Cholesterol and Alanine Transaminase Levels in Type 2 Diabetic Patients. AB - BACKGROUND: Inhibition of dipeptidyl peptidase-4 (DPP-4) has been proposed as a therapeutic target for type 2 diabetes (T2DM). Arterial stiffness, a predictor of future cardiovascular events and all-cause mortality, is augmented in these patients. However, effects of DPP-4 inhibitors on arterial stiffness remain unknown. In this study, we compared effects of anagliptin, an inhibitor of DPP-4 on arterial stiffness evaluated by cardio-ankle vascular index (CAVI) with those of an equipotent glucose-lowering agent, glimepiride in patients with T2DM. METHODS: The study involved 50 consecutive outpatients (33 males and 17 females; mean age of 72.5+/-9.5 years) who visited our hospitals for a risk-screening test or treatment for T2DM. They underwent complete history and physical examination, and determination of blood chemistry and anthropometric variables, and then were randomized to receive either anagliptin (n=26) or glimepiride (n=24) for 6 months. RESULTS: After 6-months treatment, fasting plasma glucose and HbA1c values were comparably reduced in both groups. Anagliptin, but not glimepiride treatment significantly decreased low-density lipoprotein cholesterol, malondialdehyde-modified LDL, remnant-like particle (RLP) cholesterol, CAVI, alanine transaminase (ALT), gamma-glutamyl transferase and visceral fat volume. In multiple regression analysis, absolute changes from baseline of RLP cholesterol and ALT after anagliptin treatment for 6 months (DeltaRLP cholesterol and DeltaALT) were independently correlated with DeltaCAVI (R2=0.445). CONCLUSION: The present study suggests that anagliptin may exert a beneficial effect on arterial stiffness in patients with T2DM, which is independent of its blood glucose-lowering property. Anagliptin may ameliorate arterial stiffness partly via reduction of RLP cholesterol and improvement of liver function. PMID- 27357183 TI - Lack of Evidence for Deterioration in Endothelial Function Following Ticagrelor Treatment Cessation. AB - BACKGROUND: Ticagrelor may exert pleiotropic actions, beyond platelet inhibition, which are possibly adenosine-mediated. It has been suggested that in patients with coronary artery disease (CAD) ticagrelor may influence endothelial function. OBJECTIVE: We aimed to assess the possibility of endothelial function deterioration following ticagrelor treatment cessation. METHODS: This was a prospective, observational study, in stable CAD patients with prior percutaneous coronary intervention (PCI) for acute coronary syndrome manifested 1 year earlier, under ticagrelor maintenance dose (90 mg bid) and due to discontinue ticagrelor. Endothelial function was assessed by Peripheral Arterial Tonometry (EndoPat 2000 system, Itamar Medical, Caesarea, Israel) immediately after receiving the last tablet of ticagrelor (Day 0) and at Day 2 and Day 5 post ticagrelor cessation. Reactive hyperaemia index (RHI) was calculated by automated software and endothelial dysfunction (ED) was defined as a RHI <1.67. RESULTS: We identified 30 eligible patients with endothelial function assessment pre- and post-ticagrelor cessation (86.7% men, 13.3% with diabetes and 33.3% current smokers; mean age: 63.6+/-11.5 years). The study's primary endpoint of RHI at Day 5 did not differ significantly compared with RHI at Day 0, 1.69 (1.45-2.23) vs 1.81 (1.59-2.13). ED rate did not differ significantly between Day 5 and Day 0, 40 vs 33.3%, p=0.8, respectively. No differences in RHI or ED rate were observed between Day 2 and Day 0, 1.64 (1.54-2.04) vs 1.8 1(1.59-2.13), p=0.3 and 53.3 vs 33.3%, p=0.2, respectively. In stable CAD patients there is no evidence of deterioration in endothelial function after discontinuing ticagrelor. PMID- 27357185 TI - The Role of Inflammatory Biomarkers in the Detection and Therapy of Atherosclerotic Disease. AB - The estimation of risk for atherosclerotic cardiovascular (CV) events based only on the presence of classical risk factors is often insufficient. Therefore, efforts have been made to find markers that indicate the presence of preclinical or clinical disease. Inflammation mediates all stages of the disease, from initiation to the thrombotic complications of atherosclerosis. Raised levels of several circulating markers, particularly inflammatory mediators, have been reported in subjects with atherosclerosis. Increased risk for CV events is associated with increased levels of cytokines, celladhesion molecules, P-selectin and E-selectin, and acute phase reactants, such a highsensitivity C-reactive protein and serum amyloid-A. Elevation of some of these markers predicts the outcomes of patients with acute coronary syndromes. However, because of their non specificity, these biomarkers represent only a moderate added predicting value after considering conventional CV risk factors. Consequently, recent research has focused on the detection of vulnerable plaque, using vascular bed-specific biomarkers that can help identify individuals at highest risk and help guide how to intervene to prevent CV events. Considerable progress in the understanding of the role of the inflammation in atherogenesis has opened new possibilities for the management of atherosclerosis. Recently new drugs mediating the direct inhibition of circulating markers of inflammation were developed. These drugs could provide a novel therapeutic approach and further enhance the understanding of the role of inflammation in atherosclerosis. PMID- 27357184 TI - Virulence Potential of Staphylococcus aureus Strains Isolated from Diabetic Foot Ulcers Among Patients from Southern Poland. AB - The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) was investigated among infected diabetic foot ulcers in hospitalized and nonhospitalized patients in southern Poland to assess the virulence patterns and antimicrobial resistance among these strains. MRSA was detected in 10.3% of all studied isolates, from the hospitalized patients only. The rest of the isolates was methicillin susceptible. The minimal inhibitory concentration that inhibits 50% of bacterial isolates (MIC50) for vancomycin was 1.0 mg/mL. The mupA gene was detected in six (8.8%) isolates, in one MRSA strain and five methicillin sensitive S. aureus (MSSA) strains. Among the mupA-positive strains, two were resistant to mupirocin (1 MRSA and 1 MSSA). Such results raise serious concern about the usage of mupirocin in MRSA decolonization. The pvl gene was not detected among the study isolates. The majority of isolates (70.6%) possessed the lukE gene, with no significant difference in prevalence between MRSA and MSSA isolates. An interesting finding was the presence of enterotoxin genes among the study isolates. Diabetic foot may therefore be a reservoir of bacteria, containing genes localized on mobile genetic elements that could be easily transferred to other non-pathogenic strains. The prevalence of MRSA was alarmingly high (as also suggested by others), as evaluated by the presence of the mup gene among strains, highlighting the importance of appropriate clinical management of MRSA infections in patients with diabetic foot ulcers. In this group of patients, screening of ulcer samples before antimicrobial therapy would enable informed choices regarding the selection of antimicrobial agents (e.g. octenidine, authorized for the treatment of chronic wounds) maximizing the chances of positive therapy. PMID- 27357186 TI - Type II cGMP-dependent protein kinase inhibits EGF-induced JAK/STAT signaling in gastric cancer cells. AB - Previous research has demonstrated that type II cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG II) inhibited epidermal growth factor (EGF) initiated signal transduction of MAPK-mediated, PI3K/Akt-mediated and PLCgamma1 mediated pathways through blocking EGF-induced phosphorylation/activation of EGF receptor (EGFR). As EGF/EGFR signaling also initiated signal transduction of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) mediated pathway, the present study was performed to investigate whether PKG II exerts an inhibitory effect this pathway. AGS human gastric cancer cell line was infected with adenoviral constructs encoding the cDNA of PKG II (Ad-PKG II), to increase the expression of PKG II, and treated with 8-pCPT-cGMP to activate the kinase. Western blotting was performed to detect the phosphorylation/activation of EGFR, JAK1, JAK2, STAT1 and STAT3 and the expression of cell cycle-associated proteins, including cyclin D1 and cyclin E. EGF-induced cell cycle changes were detected by flow cytometry. Transcriptional activity was determined by a reporter gene assay. The results demonstrated that EGF treatment increased the phosphorylation of EGFR, JAK1, JAK2, STAT1 and STAT3, increased the expression levels of cyclin D1 and cyclin E, promoted the cells to enter S phase, and stimulated transcriptional activity in the cells. Increased PKG II activity through infecting the cells with Ad-PKG II and activating the kinase with 8-pCPT cGMP efficiently reversed the changes caused by EGF. The results suggest that PKG II inhibits EGF-induced signal transduction of the JAK/STAT-mediated pathway and further confirms that PKG II may be a cancer inhibitor. PMID- 27357187 TI - New and safe experimental model of radiation-induced neurovascular histological changes for microsurgical research. AB - The aim is to create a new and safe experimental model of radiation-induced neurovascular histological changes with reduced morbidity and mortality for use with experimental microsurgical techniques. Seventy-two Sprague-Dawley rats (250 300 g) were divided as follows: Group I: control group, 24 rats clinically evaluated during six weeks; Group II: evaluation of acute side-effects (two-week follow-up period), 24 irradiated (20 Gy) rats; and Group III: evaluation of subacute side-effects (six-week follow-up period), 24 irradiated (20 Gy) rats. Variables included clinical assessments, weight, vascular permeability (arterial and venous), mortality and histological studies. No significant differences were observed between groups with respect to the variables studied. Significant differences were observed between groups I vs II-III regarding survival rates and histological changes to arteries, veins and nerves. Rat body weights showed progressive increases in all groups, and the mortality rate of the present model is 10.4% compared with 30-40% in the previous models. In conclusion, the designed model induces selective changes by radiotherapy in the neurovascular bundle without histological changes affecting the surrounding tissues. This model allows therapeutic experimental studies to be conducted, including the viability of microvascular and microneural sutures post radiotherapy in the cervical neurovascular bundle. PMID- 27357188 TI - The damage-associated molecular pattern HMGB1 is elevated in human alcoholic hepatitis, but does not seem to be a primary driver of inflammation. AB - The role of sterile inflammation caused by release of damage-associated molecular patterns (DAMP) remains unclear in human alcoholic hepatitis (AH). The DAMP, high mobility group box-1 protein (HMGB1) is released by tissue damage and inflammation. We aimed to investigate whether HMGB1 is a primary inflammatory driver in AH by determining HMGB1 serum levels and effects on inflammatory cells from AH patients. We measured serum HMGB1 in 34 AH patients and 10 healthy controls using ELISA. Toll-like receptor 4 (TLR4) and CD14 expressions were assessed by flow cytometry on HMGB1-stimulated peripheral blood mononuclear cells (PBMC) and ELISA was used to measure TNF-alpha and IL-1beta in the supernatants. We observed 5-fold higher serum levels of HMGB1 in AH patients at the day of diagnosis and day 30, but no associations to clinical outcome. HMGB1 stimulation increased the expression of TLR4 on CD14+-monocytes compared with unstimulated cells in the AH patients. The TNF-alpha and IL-1beta production in response to HMGB1 was diminished in AH patients. In conclusion, AH patients have increased levels of HMGB1 in their blood. This combined with an increased TLR4 expression, but an unaffected cytokine response to HMGB1 suggest that HMGB1 is not the primary driver of inflammation in AH. PMID- 27357189 TI - In Vitro Evaluation of the Dual-Diffuser Design for a Reversible Rotary Intra Aortic Ventricular Assist Device. AB - The intra-aortic ventricular assist device (IntraVAD) is a miniature intra-aortic axial-flow ventricular assist device (VAD) that works in series with the left ventricle (LV) to assist the compromised heart. Previous in vitro results have shown that the IntraVAD can successfully increase coronary perfusion and offload ventricular volume by operating in reverse-rotation control (RRc) mode. The RRc mode includes forward rotation in systole and reverse rotation (RR) in diastole. It is necessary to derive a new diffuser design that can be used for the bi directional rotation of the IntraVAD. In this work, a dual-diffuser set (DDS) was proposed to replace the conventional inducer and diffuser upstream and downstream of the pump. The DDS comprised two diffusers, located on both sides of the impeller, omitting the conventional inducer and diffuser. Different configurations of the DDS were designed and manufactured with various combinations of curved and straight blades. All configurations were initially tested in continuous flow, then in a pulsatile mock circulatory loop. A weighted normalized scalar (WNS) was proposed to comprehensively evaluate the hemodynamic effect of the DDS with different configurations. The results show that the maximum of WNS occurred when the upstream diffuser had equal numbers of curved and straight blades and the downstream diffuser had only curved blades. This indicates such a dual-diffuser design for the IntraVAD can give an optimal cardiac assistance potentially improving ventricular contractility, thereby restoring heart function. PMID- 27357190 TI - Vector competence of Aedes aegypti in transmitting Chikungunya virus: effects and implications of extrinsic incubation temperature on dissemination and infection rates. AB - BACKGROUND: Aedes aegypti is a competent arthropod vector of chikungunya virus (CHIKV). The rate at which the virus disseminate in the vector is limited by temperature of their environment which can be an important determinant of geographical and seasonal limits to transmission by the arthropods in the tropics. This study investigated the vector competence of Ae. aegypti for CHIKV at ambient temperature of 32 and 26 degrees C (Coastal and Western Kenya respectively) reared at Extrinsic Incubation Temperature (EIT) of 32 and 26 degrees C that resembles those in the two regions. METHODS: Ae. aegypti eggs were collected from coastal and Western Kenya, hatched in the insectary and reared to F1 generation. Four-day old mosquitoes were exposed to CHIKV through a membrane feeding. They were then incubated in temperatures mimicking the mean annual temperatures for Trans-Nzoia (26 degrees C) and Lamu (32 degrees C). After every 7, 10 and 13 days post infection (DPI); one third of exposed mosquitoes were sampled and assayed for virus infection and dissemination. RESULTS: The midgut infection rates (MIR) of Ae. aegypti sampled from Coastal Region was significantly (p < 0.05) higher than those sampled from Western Kenya, with no statistical differences observed for the coastal Ae. aegypti at EIT 26 and at 32 degrees C. The MIR of Ae. aegypti from the Western Region was significantly (p < 0.05) affected by the EIT, with mosquito reared at EIT 32 degrees C exhibiting higher MIR than those reared at EIT 26 degrees C. There was a significant (p < 0.05) interactive effects of the region, EIT and DPI on MIR. The disseminated infection rates for the CHIKV in Ae. aegypti in the legs (DIR-L) was higher in mosquitoes sampled from Coast regardless of the EIT while those from Western Kenya, dissemination rates were significantly higher at higher EIT of 32 degrees C. CONCLUSIONS: Vector competence was higher in mosquito populations reared under high temperatures which weakens the midgut infection barrier. Hence, suggesting Lamu population is more susceptible to CHIKV therefore having a weaker mid gut infection barrier than the Trans Nzoia population. These underscores importance of examining the course of infection at various ambient temperatures and EIT between regions mosquito populations. PMID- 27357192 TI - Regulatory Forum Opinion Piece: Review of FDA Draft Guidance Testicular Toxicity Evaluation during Drug Development Guidance for Industry. AB - In July 2015, the U.S. Food and Drug Administration (FDA) posted a new draft guidance entitled "Testicular Toxicity: Evaluation during Drug Development Guidance for Industry," with a 90-day public comment period. As the nonclinical assessment of testicular toxicity often relies on the expert interpretation of pathology affecting the male reproductive tract, this draft guidance is considered directly relevant to the toxicologic pathology community. Therefore, a working group was formed through the Scientific and Regulatory Policy Committee of the Society of Toxicologic Pathologists (STPs) to provide a detailed review of the draft guidance. Specific comments on the guidance were submitted to the FDA by the STP. The draft guidance and all comments received are currently under review with the FDA. This commentary provides a summary of the components of the draft guidance and the comments submitted by the STP with acknowledgment of different perspectives reflected in comments from other respondents. PMID- 27357191 TI - VPAC1 receptor (Vipr1)-deficient mice exhibit ameliorated experimental autoimmune encephalomyelitis, with specific deficits in the effector stage. AB - BACKGROUND: Vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase activating polypeptide (PACAP) are two highly homologous neuropeptides. In vitro and ex vivo experiments repeatedly demonstrate that these peptides exert pronounced immunomodulatory (primarily anti-inflammatory) actions which are mediated by common VPAC1 and VPAC2 G protein-coupled receptors. In agreement, we have shown that mice deficient in PACAP ligand or VPAC2 receptors exhibit exacerbated experimental autoimmune encephalomyelitis (EAE). However, we observed that VIP-deficient mice are unexpectedly resistant to EAE, suggesting a requirement for this peptide at some stage of disease development. Here, we investigated the involvement of VPAC1 in the development of EAE using a VPAC1 deficient mouse model. METHODS: EAE was induced in wild-type (WT) and VPAC1 knockout (KO) mice using myelin oligodendrocyte glycoprotein 35-55 (MOG35-55), and clinical scores were assessed continuously over 30 days. Immune responses in the spinal cords were determined by histology, real-time PCR and immunofluorescence, and in the draining lymph nodes by antigen-recall assays. The contribution of VPAC1 expression in the immune system to the development of EAE was evaluated by means of adoptive transfer and bone marrow chimera experiments. In other experiments, VPAC1 receptor analogs were given to WT mice. RESULTS: MOG35-55-induced EAE was ameliorated in VPAC1 KO mice compared to WT mice. The EAE-resistant phenotype of VPAC1 KO mice correlated with reduced central nervous system (CNS) histopathology and cytokine expression in the spinal cord. The immunization phase of EAE appeared to be unimpaired because lymph node cells from EAE-induced VPAC1 KO mice stimulated in vitro with MOG exhibited robust proliferative and Th1/Th17 responses. Moreover, lymph node and spleen cells from KO mice were fully capable of inducing EAE upon transfer to WT recipients. In contrast, WT cells from MOG-immunized mice did not transfer the disease when administered to VPAC1 KO recipients, implicating a defect in the effector phase of the disease. Bone marrow chimera studies suggested that the resistance of VPAC1-deficient mice was only minimally dependent on the expression of this receptor in the immunogenic/hematopoietic compartment. Consistent with this, impaired spinal cord inductions of several chemokine mRNAs were observed in VPAC1 KO mice. Finally, treatment of WT mice with the VPAC1 receptor antagonist PG97 269 before, but not after, EAE induction mimicked the clinical phenotype of VPAC1 KO mice. CONCLUSIONS: VPAC1 gene loss impairs the development of EAE in part by preventing an upregulation of CNS chemokines and invasion of inflammatory cells into the CNS. Use of VPAC1 antagonists in WT mice prior to EAE induction also support a critical role for VPAC1 signaling for the development of EAE. PMID- 27357194 TI - Regional variation of patient behaviour and reasons for consultation in the general practice of Northern Germany: protocol for an observational study. AB - INTRODUCTION: Inappropriate supply and an increasing demand on the healthcare system have been of concern for health policy in Germany for at least 15 years. In the primary care setting, this especially relates to an undersupply of general practitioners (GPs) in the countryside. In addition, there seem to be other regional differences, for example, a difference in accessing primary and secondary care between rural and urban areas. Despite these findings, regional differences in health services have not been studied extensively in Germany. Therefore, this study aims to explore regional variations of patient populations and reasons for accessing primary medical care. METHODS AND ANALYSIS: We will conduct a cross-sectional observational study based on standardised interviews with 240 GPs and ~1200 patients. Data collection started on 10 June 2015 and will probably be completed by 31 October 2016. We will include all districts and cities within 100 km from Hamburg and assign them according to the type of regions: rural, urban and environs. All eligible GPs will be invited to participate. Each practice will recruit up to 15 patients, aged 18 years or older. Questionnaires are based on a preliminary qualitative study and were pretested. Data will be analysed with descriptive statistics and regression modelling strategies adjusted for confounders and the GP-induced cluster structure. ETHICS AND DISSEMINATION: Our study was approved by the Ethics Committee of the Medical Association of Hamburg and is conducted in accordance with the Declaration of Helsinki. Study participants give written informed consent before data collection and data is pseudonymised. Survey data and person identifiers are stored separately in locked cabinets and have restricted availability. The results of our study will be presented at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02558322; Pre results. PMID- 27357193 TI - Perceptions of risk and predictive testing held by the first-degree relatives of patients with rheumatoid arthritis in England, Austria and Germany: a qualitative study. AB - OBJECTIVES: The family members of patients with rheumatoid arthritis (RA) are at increased risk of developing RA and are potential candidates for predictive testing. This study explored the perceptions of first-degree relatives of people with RA about being at risk of RA and engaging in predictive testing. METHODS: 34 first-degree relatives (siblings and offspring) of patients with RA from the UK, Germany and Austria participated in semistructured interviews about their perceptions of RA risk and the prospect of predictive testing. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: First-degree relatives were aware of their susceptibility to RA, but were unsure of the extent of their risk. When considering their future risk, some relatives were concerned about the potential impact that RA would have on their lives. Relatives were concerned that knowing their actual risk would increase their anxiety and would affect decisions about their future. Also, relatives were concerned about the levels of uncertainty associated with predictive testing. Those in favour of knowing their future risk felt that they would need additional support to understand the risk information and cope with the emotional impact of this information. CONCLUSIONS: Identifying individuals at risk of RA may allow targeted interventions to reduce the risk and consequence of future disease; however, relatives have concerns about predictive testing and risk information. The development of strategies to quantify and communicate risk needs to take these views into account and incorporate approaches to mitigate concerns and minimise the psychological impact of risk information. PMID- 27357195 TI - Retrospective analysis of changing characteristics of treatment-seeking smokers: implications for further reducing smoking prevalence. AB - OBJECTIVE: The goal of the current study was to empirically compare successive cohorts of treatment-seeking smokers who enrolled in randomised clinical trials in a region of the USA characterised by strong tobacco control policies and low smoking prevalence, over the past three decades. DESIGN: Retrospective treatment cohort comparison. SETTING: Data were collected from 9 randomised clinical trials conducted at Stanford University and the University of California, San Francisco, between 1990 and 2013. PARTICIPANTS: Data from a total of 2083 participants were included (Stanford, n=1356; University of California San Francisco, n=727). PRIMARY AND SECONDARY OUTCOMES: One-way analysis of variance and covariance, chi(2) and logistic regression analyses were used to examine relations between nicotine dependence, cigarettes per day, depressive symptoms and demographic characteristics among study cohorts. RESULTS: Similar trends were observed at both settings. When compared to earlier trials, participants in more recent trials smoked fewer cigarettes, were less nicotine-dependent, reported more depressive symptoms, were more likely to be male and more likely to be from a minority ethnic/racial group, than those enrolled in initial trials (all p's<0.05). Analysis of covariances revealed that cigarettes per day, nicotine dependence and current depressive symptom scores were each significantly related to trial (all p's<0.001). CONCLUSIONS: Our findings suggest that more recent smoking cessation treatment-seeking cohorts in a low prevalence region were characterised by less smoking severity, more severe symptoms of depression and were more likely to be male and from a minority racial/ethnic group. PMID- 27357196 TI - Estimated association between dwelling soil contamination and internal radiation contamination levels after the 2011 Fukushima Daiichi nuclear accident in Japan. AB - OBJECTIVES: Measurement of soil contamination levels has been considered a feasible method for dose estimation of internal radiation exposure following the Chernobyl disaster by means of aggregate transfer factors; however, it is still unclear whether the estimation of internal contamination based on soil contamination levels is universally valid or incident specific. METHODS: To address this issue, we evaluated relationships between in vivo and soil cesium 137 (Cs-137) contamination using data on internal contamination levels among Minamisoma (10-40 km north from the Fukushima Daiichi nuclear power plant), Fukushima residents 2-3 years following the disaster, and constructed three models for statistical analysis based on continuous and categorical (equal intervals and quantiles) soil contamination levels. RESULTS: A total of 7987 people with a mean age of 55.4 years underwent screening of in vivo Cs-137 whole body counting. A statistically significant association was noted between internal and continuous Cs-137 soil contamination levels (model 1, p value <0.001), although the association was slight (relative risk (RR): 1.03 per 10 kBq/m(2) increase in soil contamination). Analysis of categorical soil contamination levels showed statistical (but not clinical) significance only in relatively higher soil contamination levels (model 2: Cs-137 levels above 100 kBq/m(2) compared to those <25 kBq/m(2), RR=1.75, p value <0.01; model 3: levels above 63 kBq/m(2) compared to those <11 kBq/m(2), RR=1.45, p value <0.05). CONCLUSIONS: Low levels of internal and soil contamination were not associated, and only loose/small associations were observed in areas with slightly higher levels of soil contamination in Fukushima, representing a clear difference from the strong associations found in post-disaster Chernobyl. These results indicate that soil contamination levels generally do not contribute to the internal contamination of residents in Fukushima; thus, individual measurements are essential for the precise evaluation of chronic internal radiation contamination. PMID- 27357197 TI - Risk factors associated with RSV hospitalisation in the first 2 years of life, among different subgroups of children in NSW: a whole-of-population-based cohort study. AB - BACKGROUND: Data on risk factors for respiratory syncytial virus (RSV)-associated hospitalisation in Australian children may be informative for preventive measures. METHODS: A whole-of-population-based study was conducted to identify comparable risk factors for RSV hospitalisation in different subgroups of children aged <2 years in New South Wales. The cohort was divided into Indigenous children and high-risk and standard risk non-Indigenous children. Data on risk factors were obtained from the Perinatal Data Collection. RSV hospitalisations were ascertained from the Admitted Patient Data Collection. Adjusted HRs were calculated for each subgroup. Population-attributable risk associated with risk factors was estimated. RESULTS: Four factors were associated with increased risk of RSV hospitalisation: maternal smoking during pregnancy, male sex, multiparity and birth during the first half of the RSV season. Increase in relative socioeconomic advantage was associated with decreased risk of hospitalisation. Among high and standard risk non-Indigenous children, the hazard was approximately double for children born to multiparous women compared to those born to primiparous women and among Indigenous children the hazard was approximately double among those born during the first half of the RSV season. Maternal smoking during pregnancy was associated with a 26-45% increased risk across subgroups and accounted for 17% (95% CI 9.3% to 24%) of RSV hospitalisations in Indigenous children, 5% (95% CI 2.5% to 8%) in high-risk and 6% (95% 5% to 7%) in standard risk non-Indigenous children. DISCUSSION: Promoting avoidance of smoking during pregnancy may help in lowering the disease burden, with Indigenous children likely to benefit most. PMID- 27357198 TI - Group-based exercise in daily clinical practice to improve physical fitness in men with prostate cancer undergoing androgen deprivation therapy: study protocol. AB - INTRODUCTION: Level 1 evidence supports the use of supervised exercise to mitigate the adverse effects of androgen deprivation therapy (ADT) in men with prostate cancer. The data, however, have been generated in controlled research settings and might not be transferable to daily clinical practice. This article describes the design of an ongoing prospective observational study to evaluate the potential benefits of exercise in daily clinical practice. METHODS AND ANALYSIS: Men diagnosed with prostate cancer starting or already receiving ADT at our facility are invited to participate in a 12-week exercise programme implemented as the standard of care. Exclusion criteria are opioid-demanding treatment for skeletal pain, an Eastern Cooperative Oncology Group (ECOG) performance status above 2 or the inability to perform floor and machine exercises independently. The intervention consists of an initial educational session of 11/2 hours followed by 12 weeks of group-based supervised training two times a week. The focus of the exercise is progressive resistance training in combination with aerobic training. Participants are measured at baseline, after 12 weeks and after 24 weeks as part of the programme. Primary endpoints of this study are changes in physical fitness evaluated by the 30 s Chair-Stand Test and Graded Cycling Test with Talk Test. Secondary endpoints include changes in quality of life, body composition and safety of exercise. Inclusion started in August 2014, with 169 participants being included by December 2015. ETHICS AND DISSEMINATION: The study has been reviewed by the Scientific Ethical Committee of the Capital Region of Denmark (reference number H-3-2013-FSP39). The results of the study will be published in peer-reviewed international journals and will be presented at national and international conferences and symposiums. TRIAL REGISTRATION NUMBER: NCT02631681; Pre-results. PMID- 27357199 TI - High birth weight in a suburban hospital in Cameroon: an analysis of the clinical cut-off, prevalence, predictors and adverse outcomes. AB - BACKGROUND AND AIMS: High birth weight (HBW) increases the risk of maternal and fetal morbidity and mortality. Its prevalence and adverse outcomes may be reduced if risk factors are identified and managed during pregnancy. The cut-off value for HBW remains debatable. The objectives of this study were to identify the optimal cut-off value and determine the prevalence, predictors and adverse outcomes of HBW in a suburban area of Cameroon. DESIGN: A 6-year retrospective register analysis and a 3-month prospective phase. SETTING: A secondary care level (regional) hospital in the city of Buea (southwest region of Cameroon). PARTICIPANTS: Women who delivered in this hospital over a 6-year period (retrospective phase) and consenting pregnant mothers and their infants (singletons, born at >28 weeks gestation) (prospective phase). OUTCOME MEASURES: 90th centile of birth weights; prevalence of HBW defined as birth weight above the 90th centile; sociodemographic, maternal and obstetrical factors associated with HBW; maternal and neonatal adverse outcomes of HBW. RESULTS: Of the 4941 newborns reviewed in registers, the 90th centile of birth weights was 3850 g. Using this new cut-off, we obtained a prevalence of 14.0% for HBW in the 200 newborns included in the prospective phase. This was significantly higher than the prevalence (9.5%) yielded when the traditional cut-off of 4000 g was used (p=0.003). None of the factors assessed was independently associated with HBW. Newborns with HBW were more likely to have shoulder dystocia (p<0.01), and their mothers more likely to suffer from prolonged labour (p=0.01) and postpartum haemorrhage (p<0.01). CONCLUSIONS: The results of this study suggest that the cut off for HBW in this population should be 3850 g. Thus, 3 of every 10 babies born with HBW in this hospital are likely not receiving optimal postnatal care because 4000 g is currently used to qualify for additional support. PMID- 27357200 TI - Young adolescent girls are at high risk for adverse pregnancy outcomes in sub Saharan Africa: an observational multicountry study. AB - OBJECTIVES: One of Africa's most important challenges is to improve maternal and neonatal health. The identification of groups at highest risk for adverse pregnancy outcomes is important for developing and implementing targeted prevention programmes. This study assessed whether young adolescent girls constitute a group at increased risk for adverse birth outcomes among pregnant women in sub-Saharan Africa. SETTING: Data were collected prospectively as part of a large randomised controlled clinical trial evaluating intermittent preventive treatment of malaria in pregnancy (NCT00811421-Clinical Trials.gov), conducted between September 2009 and December 2013 in Benin, Gabon, Mozambique and Tanzania. PARTICIPANTS: Of 4749 participants, pregnancy outcomes were collected for 4388 deliveries with 4183 live births including 83 multiple gestations. Of 4100 mothers with a singleton live birth delivery, 24% (975/4100) were adolescents (<=19 years of age) and 6% (248/4100) were aged <=16 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes of this predefined analysis were preterm delivery and low birth weight. RESULTS: The overall prevalence of low birthweight infants and preterm delivery was 10% (371/3851) and 4% (159/3862), respectively. Mothers aged <=16 years showed higher risk for the delivery of a low birthweight infant (OR: 1.96; 95% CI 1.35 to 2.83). Similarly, preterm delivery was associated with young maternal age (<=16 years; OR: 2.62; 95% CI 1.59 to 4.30). In a subanalysis restricted to primiparous women: preterm delivery, OR 4.28; 95% CI 2.05 to 8.93; low birth weight, OR: 1.29; 95% CI 0.82 to 2.01. CONCLUSIONS: Young maternal age increases the risk for adverse pregnancy outcomes and it is a stronger predictor for low birth weight and preterm delivery than other established risk factors in sub-Saharan Africa. This finding highlights the need to improve adolescent reproductive health in sub-Saharan Africa. TRIAL REGISTRATION NUMBER: NCT00811421; Post-results. PMID- 27357202 TI - Improved Physical Activity Screening Enhances Intervention Effectiveness in Ethnic Minority Women: A Longitudinal Study. AB - This study identified inconsistencies in physical activity (PA) reported at screening and baseline of a 6-month health promotion intervention and explored how these inconsistencies influenced intervention effectiveness in African American and Hispanic women. Participants completed a telephone screener to determine eligibility for a PA intervention. Inactive participants (<=90 minutes of PA/week) were invited to a baseline assessment, where they completed the International Physical Activity Questionnaire, measuring work, transportation, gardening/housework, and leisure-time PA. Women returned after 6 months to complete an identical post-intervention assessment. Despite being screened as inactive, baseline Questionnaire data indicated that 85.0% of participants (N = 274, M age = 44.6 years, M body mass index = 34.8 kg/m2) were active (>90 minutes of PA/week). Women who reported any work-related PA were 20.9 times more likely to be active at baseline than those who did not (p < .001). Participants who were inactive at both screening and baseline reported greater increases in domestic and gardening PA and total PA from baseline to postintervention (ps < .05). Overweight/obese ethnic minority women may misreport being physically inactive during screening if specific questions about type of PA are not included. Post hoc analyses controlling for screening inaccuracies may improve effectiveness of PA interventions and help intervention programs reach women who may benefit the most. PMID- 27357201 TI - Advanced Age Alters Monocyte and Macrophage Responses. AB - SIGNIFICANCE: With the growing population of baby boomers, there is a great need to determine the effects of advanced age on the function of the immune system. Recent Advances: It is universally accepted that advanced age is associated with a chronic low-grade inflammatory state that is referred to as inflamm-aging, which alters the function of both immune and nonimmune cells. Mononuclear phagocytes play a central role in both the initiation and resolution of inflammation in multiple organ systems and exhibit marked changes in phenotype and function in response to environmental cues, including the low levels of pro inflammatory mediators seen in the aged. CRITICAL ISSUES: Although we know a great deal about the function of immune cells in young adults and there is a growing body of literature focusing on aging of the adaptive immune system, much less is known about the impact of age on innate immunity and the critical role of the mononuclear phagocytes in this process. FUTURE DIRECTIONS: In this article, there is a focus on the tissue-specific monocyte and macrophage subsets and how they are altered in the aged milieu, with the hope that this compilation of observations will spark an expansion of research in the field. Antioxid. Redox Signal. 25, 805-815. PMID- 27357203 TI - Do Neighborhood Demographics Modify Walking Group Intervention Effectiveness in Urban Neighborhoods? AB - OBJECTIVES: We assessed the effects of neighborhood composition on effectiveness of the Walk Your Heart to Health (WYHH) intervention in promoting physical activity and reducing cardiovascular risk (CVR) in low-to-moderate-income, predominantly non-Latino Black (NLB) and Latino communities. METHOD: Multilevel models assessed modifying effects of neighborhood composition on (1) WYHH adherence/participation at 8 weeks and 32 weeks, (2) associations between participation and steps, and (3) associations between steps and CVR. RESULTS: Approximately 90% of participants were women. Neither neighborhood poverty nor racial composition modified intervention participation at 8 weeks. At 32 weeks, residents of high percentage-NLB neighborhoods that also had high poverty rates had reduced participation. Neighborhood composition did not modify associations between participation and steps or between steps and CVR. Neighborhood percentage poverty and NLB were positively associated with CVR. CONCLUSION: Positive associations between participation in the WYHH program and physical activity, and CVR did not differ by neighborhood composition. Efforts to address challenges to long-term participation are warranted for residents of racially segregated, high poverty neighborhoods. Residents of racially segregated neighborhoods with high concentrations of poverty experience disproportionately high risk for cardiovascular disease and can benefit from interventions such as WYHH that increase physical activity and reduce CVR. PMID- 27357204 TI - Presenilin E318G variant and Alzheimer's disease risk: the Cache County study. AB - BACKGROUND: Alzheimer's disease is the leading cause of dementia in the elderly and the third most common cause of death in the United States. A vast number of genes regulate Alzheimer's disease, including Presenilin 1 (PSEN1). Multiple studies have attempted to locate novel variants in the PSEN1 gene that affect Alzheimer's disease status. A recent study suggested that one of these variants, PSEN1 E318G (rs17125721), significantly affects Alzheimer's disease status in a large case-control dataset, particularly in connection with the APOEepsilon4 allele. METHODS: Our study looks at the same variant in the Cache County Study on Memory and Aging, a large population-based dataset. We tested for association between E318G genotype and Alzheimer's disease status by running a series of Fisher's exact tests. We also performed logistic regression to test for an additive effect of E318G genotype on Alzheimer's disease status and for the existence of an interaction between E318G and APOEepsilon4. RESULTS: In our Fisher's exact test, it appeared that APOEepsilon4 carriers with an E318G allele have slightly higher risk for AD than those without the allele (3.3 vs. 3.8); however, the 95 % confidence intervals of those estimates overlapped completely, indicating non-significance. Our logistic regression model found a positive but non-significant main effect for E318G (p = 0.895). The interaction term between E318G and APOEepsilon4 was also non-significant (p = 0.689). CONCLUSIONS: Our findings do not provide significant support for E318G as a risk factor for AD in APOEepsilon4 carriers. Our calculations indicated that the overall sample used in the logistic regression models was adequately powered to detect the sort of effect sizes observed previously. However, the power analyses of our Fisher's exact tests indicate that our partitioned data was underpowered, particularly in regards to the low number of E318G carriers, both AD cases and controls, in the Cache county dataset. Thus, the differences in types of datasets used may help to explain the difference in effect magnitudes seen. Analyses in additional case control datasets will be required to understand fully the effect of E318G on Alzheimer's disease status. PMID- 27357206 TI - Report of the European Society of Cardiology Cardiovascular Round Table regulatory workshop update of the evaluation of new agents for the treatment of acute coronary syndrome: Executive summary. AB - Regulatory authorities interpret the results of randomized controlled trials according to published principles. The European Medicines Agency (EMA) is planning a revision of the 2000 and 2003 guidance documents on clinical investigation of new medicinal products for the treatment of acute coronary syndrome (ACS) to achieve consistency with current knowledge in the field. This manuscript summarizes the key output from a collaborative workshop, organized by the Cardiovascular Round Table and the European Affairs Committee of the European Society of Cardiology, involving clinicians, academic researchers, trialists, European and US regulators, and pharmaceutical industry researchers. Specific questions in four key areas were selected as priorities for changes in regulatory guidance: patient selection, endpoints, methodologic issues and issues related to the research for novel agents. Patients with ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) should be studied separately for therapies aimed at the specific pathophysiology of either condition, particularly for treatment of the acute phase, but can be studied together for other treatments, especially long-term therapy. Unstable angina patients should be excluded from acute phase ACS trials. In general, cardiovascular death and reinfarction are recommended for primary efficacy endpoints; other endpoints may be considered if specifically relevant for the therapy under study. New agents or interventions should be tested against a background of evidence-based therapy with expanded follow-up for safety assessment. In conclusion, new guidance documents for randomized controlled trials in ACS should consider changes regarding patient and endpoint selection and definitions, and trial designs. Specific requirements for the evaluation of novel pharmacological therapies need further clarification. PMID- 27357205 TI - Small GTP-binding protein PdRanBP regulates vascular tissue development in poplar. AB - BACKGROUND: Previous research has demonstrated that ectopic expression of Ran binding protein (RanBP) in Arabidopsis results in more axillary buds and reduced apical dominance compared to WT plants. However, the function of RanBP in poplar, which has very typical secondary growth, remains unclear. Here, the Populus deltoides (Marsh.) RanBP gene (PdRanBP) was isolated and functionally characterized by ectopic expression in a hybrid poplar (P. davidiana Dode * P. bolleana Lauche). RESULTS: PdRanBP was predominantly expressed in leaf buds and tissues undergoing secondary wall expansion, including immature xylem and immature phloem in the stem. Overexpression of PdRanBP in poplar increased the number of sylleptic branches and the proportion of cells in the G2 phase of the cell cycle, retarded plant growth, consistently decreased the size of the secondary xylem and secondary phloem zones, and reduced the expression levels of cell wall biosynthesis genes. The downregulation of PdRanBP facilitated secondary wall expansion and increased stem height, the sizes of the xylem and phloem zones, and the expression levels of cell wall biosynthesis genes. CONCLUSIONS: These results suggest that PdRanBP influences the apical and radial growth of poplar trees and that PdRanBP may regulate cell division during cell cycle progression. Taken together, our results demonstrated that PdRanBP is a nuclear, vascular tissue development-associated protein in P. deltoides. PMID- 27357207 TI - Development of a subgenomic clone system for Kyasanur Forest disease virus. AB - Emerging tropical viruses pose an increasing threat to public health because social, economic and environmental factors such as global trade and deforestation allow for their migration into previously unexposed populations and ecological niches. Among such viruses, Kyasanur Forest disease virus (KFDV) deserves particular recognition because it causes hemorrhagic fever. This work describes the completion of an antiviral testing platform (subgenomic system) for KFDV that could be used to quickly and safely screen compounds capable of inhibiting KFDV replication without the requirement for high containment, as the structural genes have been replaced with a luciferase reporter gene precluding the generation of infectious particles. The coordination of KFDV kinetics with the replication characteristics of the subgenomic system has provided additional insight into the timing of flavivirus replication events, as the genetically engineered KFDV genome began replication as early as 2h post cellular entry. Possession of such antiviral testing platforms by public health agencies should accelerate the testing of antiviral drugs against emerging or recently emerged viruses mitigating the effects of their disease and transmission. PMID- 27357208 TI - A recombinant plasmid containing CpG motifs as a novel vaccine adjuvant for immune protection against herpes simplex virus 2. AB - The aim of the present study was to evaluate the efficacy of a herpes simplex virus type 2 (HSV-2) DNA vaccine co-immunized with a plasmid adjuvant containing CpG motifs. A novel eukaryotic expression plasmid vector containing kanamycin resistance gene (pcDNA3Kan) was acquired from pET-28a(+) and pcDNA3 plasmids. A gene encoding full length HSV-2 glycoprotein D (gD) was amplified from the pcDNA3 gD plasmid, which was cloned into pcDNA3Kan resulting in the construction of the recombinant plasmid pcDNA3Kan-gD (pgD). A DNA segment containing 8 CpG motifs was synthesized, and cloned into pcDNA3Kan, resulting in the recombinant plasmid pcDNA3Kan-CpG (pCpG). Mice were co-inoculated with pgD (used as a DNA vaccine) and pCpG (used as an adjuvant) by bilateral intramuscular injection. Mice inoculated with pgD+pCpG showed higher titers of antibodies than those inoculated with the DNA vaccine alone (P<0.05). In addition, mice inoculated with pgD+pCpG showed the highest percentage of CD4+ T cells in the blood of all the groups (P<0.05). Thus, the present study demonstrated that pCpG could stimulate the HSV 2 DNA vaccine to induce a stronger cell-mediated immune response than the DNA vaccine alone. The aim of the present study was to evaluate the efficacy of a HSV 2 DNA vaccine (pgD) co-immunized with a plasmid adjuvant containing CpG motifs (pCpG). Whether the pCpG would be able to stimulate the pgD to induce a stronger immune response compared with pgD alone. PMID- 27357209 TI - Delivery of plasmid encoding interleukin-12 gene into hepatocytes by conjugated polyethylenimine-based nanoparticles. AB - In the present investigation, polyethylenimine (PEI) was conjugated with succinic anhydride at four substitution degrees and the efficiency of the modified PEI derivatives in transferring the plasmid encoding interleukin-12 gene was evaluated. The results revealed that the conjugated PEI derivatives enhanced the transfection efficiency by up to 3-fold relative to unmodified PEI, with the highest increase occurring at conjugation degrees around 30%. The results demonstrated the ability of the modified PEI derivatives in condensation of the plasmid into the nanoparticles in the size range of approximately 100 nm. Also, the PEI derivatives exhibited substantial decrease in cell-induced toxicity. PMID- 27357210 TI - First-line therapy in HER2 positive metastatic breast cancer: is the mosaic fully completed or are we missing additional pieces? AB - The discovery of human epidermal growth factor receptor 2 (HER2) and its role in the biology of breast cancer and the subsequent development of HER2-targeted therapies, have dramatically improved clinical outcomes for women with early stage and advanced HER2-positive breast cancer (BC).HER-2 targeted therapies represent a major step forward in achieving the goal of delivering individualized targeted therapy for BC, and trastuzumab was the first anti-HER-2 strategy to be approved for treatment of HER-2 positive BC. This review discusses the treatment of metastatic HER2-positive BC and describes efficacy and safety of novel anti HER2 target therapies in first-line metastatic settings and the future challenges include refining such treatments, reducing toxicity and simultaneously developing innovative therapies. Furthermore, combinations of trastuzumab and drugs targeting the downstream pathway are described.In the next future will be possible to use an ample armamentarium of combination therapies directed against HER2 and key signaling components integrated in the HER network. This approach will allow clinicians to tailor the management of the individual patient on the basis of tumor- specific biomarker profiles.There is an urgent need for prospective biomarker-driven trials to identify patients for whom targeting is cost-effective. PMID- 27357211 TI - Self-perception and knowledge of evidence based medicine by physicians. AB - BACKGROUND: The influence, legitimacy and application of Evidence Based Medicine (EBM) in the world is growing as a tool that integrates, the best available evidence to decision making in patient care. Our goal was to identify the relationship between self-perception about the relevance of Evidence Based Medicine (EBM) and the degree of basic knowledge of this discipline in a group of physicians. METHODS: A survey was carried out in a third level public hospital in Mexico City. Self-perception was measured by means of a structured scale, and the degree of knowledge through parameter or "rubrics" methodology. RESULTS: A total of 320 questionnaires were given to 55 medical students (17 %); 45 pre-graduate medical interns (14 %); 118 medical residents (37 %) and 102 appointed physicians of different specialties (32 %). Self-perception of EBM: The majority of those surveyed (n = 274, 86 %) declared that they were very or moderately familiar with EBM. The great majority (n = 270, 84 %) believe that EBM is very important in clinical practice and 197 physicians (61 %) said that they implement it always or usually. The global index of self-perception was 75 %. Knowledge of EBM: Definition of EBM; Seven of those surveyed (2 %) included 3 of the 4 characteristics of the definition, 82 (26 %) mentioned only two characteristics of the definition, 152 (48 %) mentioned only one characteristic and 79 (25 %) did not include any characteristic of EBM. Phases of the EBM process: The majority of those surveyed (n = 218, 68 %) did not include the steps that characterize the practice of EBM, of which 79 participants (25 %) mentioned elements not related to it. The global index of knowledge was 19 %. CONCLUSIONS: The majority of the surveyed physicians have a high self-perception of the relevance of EBM. In spite of this, the majority of them did not know the characteristics that define the EBM and phases of the process for its practice. A major discrepancy was found between self-perception and the level of basic knowledge of EBM among the surveyed physicians. PMID- 27357213 TI - Review article: Updated resuscitation guidelines for 2016: A summary of the Australian and New Zealand Committee on Resuscitation recommendations. AB - This review paper summarises the key changes made to the resuscitation guidelines used in Australia and New Zealand. They were released by the Australian and New Zealand Committee on Resuscitation in January 2016. These are local adaptations of the evidence previously published in October 2015 by the International Liaison Committee on Resuscitation (ILCOR). They are presented across the main working groups in ILCOR: ALS, BLS, paediatrics, neonates, acute coronary syndromes, first aid and 'Education, Implementation and Teams'. PMID- 27357214 TI - Regulation of NPY and alpha-MSH expression by estradiol in the arcuate nucleus of Wistar female rats: a stereological study. AB - OBJECTIVES: Feeding behavior in both animals and humans is modulated by estrogens, as shown by the increased adiposity observed in women and rats upon the drop of estradiol levels at menopause. Estradiol action on food intake is mediated through its cognate receptors within several hypothalamic nuclei, namely the arcuate nucleus (ARN). The ARN contains two neuronal populations expressing peptides that exert opposing effects on the central control of feeding: the orexigenic neuropeptide Y (NPY) and the anorexigenic alpha-melanocyte-stimulating hormone (alpha-MSH). METHODS: To understand the role played by estradiol in the modulation of food intake, we have used an animal model of cyclic 17beta estradiol benzoate (EB) administration and stereological methods to estimate the total number of neurons immunoreactive for NPY and alpha-MSH in the ARN of ovariectomized rats. RESULTS: Present results show that the experimentally induced EB cyclicity prompted a decrease in food consumption and in body weight. Data also show that ovariectomy induced an increase in NPY expression and a decrease in alpha-MSH expression in the ARN that were reverted by EB administration. Conversely, EB blocked the expression of NPY and increased the synthesis of alpha-MSH in ARN neurons, without affecting the overall sum of NPY and alpha-MSH neurons. DISCUSSION: These results suggest that estradiol affects food intake and, consequently, body weight gain, through an overriding mechanism superimposed in the physiological balance between both peptides in the ARN of female rats. PMID- 27357212 TI - Analysis of primary visual cortex in dementia with Lewy bodies indicates GABAergic involvement associated with recurrent complex visual hallucinations. AB - Dementia with Lewy bodies (DLB) patients frequently experience well formed recurrent complex visual hallucinations (RCVH). This is associated with reduced blood flow or hypometabolism on imaging of the primary visual cortex. To understand these associations in DLB we used pathological and biochemical analysis of the primary visual cortex to identify changes that could underpin RCVH. Alpha-synuclein or neurofibrillary tangle pathology in primary visual cortex was essentially absent. Neurone density or volume within the primary visual cortex in DLB was also unchanged using unbiased stereology. Microarray analysis, however, demonstrated changes in neuropeptide gene expression and other markers, indicating altered GABAergic neuronal function. Calcium binding protein and GAD65/67 immunohistochemistry showed preserved interneurone populations indicating possible interneurone dysfunction. This was demonstrated by loss of post synaptic GABA receptor markers including gephyrin, GABARAP, and Kif5A, indicating reduced GABAergic synaptic activity. Glutamatergic neuronal signalling was also altered with vesicular glutamate transporter protein and PSD-95 expression being reduced. Changes to the primary visual cortex in DLB indicate that reduced GABAergic transmission may contribute to RCVH in DLB and treatment using targeted GABAergic modulation or similar approaches using glutamatergic modification may be beneficial. PMID- 27357215 TI - Twenty-six circulating antigens and two novel diagnostic candidate molecules identified in the serum of canines with experimental acute toxoplasmosis. AB - BACKGROUND: The protozoan Toxoplasma gondii is a pathogen that causes severe opportunistic disease in a wide range of hosts. Efficient methods to diagnose acute T. gondii infection are essential for the administration of appropriate treatments and to reduce economic losses. In animals with acute infections, circulating antigens (CAgs) were detected as early as two days post-infection; these CAgs were reliable diagnostic indicators of acute infection. However, only a limited number of CAgs have been identified to date. The objective of this study was to identify a broader spectrum of CAgs and to explore novel diagnostic candidates in serum. METHODS: A canine model of acute toxoplasmiosis was established. For this purpose, six dogs were infected by intraperitoneal inoculation of tachyzoites. The CAgs spectrum in the serum was identified with the immunoprecipitation-shotgun approach. Two CAgs with low homology to other species, coronin protein (TgCOR) and ELMO protein (TgELMO), were heterologously expressed in Escherichia coli. Polyclonal antibodies against these two proteins were prepared, and the presence of these proteins in the serum was verified by Western blotting. The two CAgs were detected and evaluated by indirect ELISA methods. RESULTS: The CAgs levels peaked between two and five days after inoculation, and twenty-six CAgs were identified. Western blotting showed the presence of the two proteins in the serum during acute infection. Based on ELISA tests, the two CAgs were detected during acute infection. CONCLUSIONS: We identified twenty-six CAgs in the serum of canines with experimental acute toxoplasmosis and discovered two novel diagnostic candidates. We also provide new insights into the diagnosis of acute toxoplasmosis. PMID- 27357217 TI - Interaction of the Antimicrobial Peptides Rhesus theta-Defensin and Porcine Protegrin-1 with Anionic Phospholipid Monolayers. AB - A combination of Langmuir isotherm, Brewster angle microscopy (BAM), and neutron reflectivity studies have been performed to gain insight into the effects on model bacterial cell membranes of the antimicrobial peptides, Rhesus theta defensin 1 (RTD-1), and porcine protegrin 1 (PG-1). The peptides were interacted with monolayers spread at the air-water interface and prepared from a 3:1 molar mixture of phosphatidylethanolamine and phosphatidylglycerol used to approximate the cell membranes of Gram positive bacteria. The Langmuir film balance measurements show that both peptides perturb the lipid monolayers causing an increase in surface pressure, and the BAM studies show that each results in the formation of small domains within the lipid films, around 5 MUm diameter. The overall change in monolayer surface pressure caused by PG-1, however, is a little more pronounced than that due to RTD-1 (+8.5 mN.m(-1) vs +5.5 mN.m(-1)), and the rate of its initial interaction with the monolayer is a little more rapid than that for RTD-1. The neutron reflectivity studies also show differences for PG-1 and RTD-1, with the model fits to these data showing that the more amphiphilic PG 1 becomes fully embedded within the lipid film-causing an extension of the lipid acyl chains but leaving the thickness of the lipid headgroup layer unaffected while RTD-1 is seen to insert less deeply-causing the same extension of the lipid acyl chains as PG-1 but also causing a significant increase in thickness of the lipid headgroup layer. The various differing effects of the two peptides on anionic lipid monolayers are discussed in the context of their differing hemolytic activities, and their proposed differing propensities to form transmembrane pores. PMID- 27357216 TI - Antiarrhythmic therapy as an adjuvant to promote post pulmonary vein isolation success-a meta-analysis. AB - BACKGROUND: Three months of empirical antiarrhythmic drug (AAD) therapy after atrial fibrillation ablation (AFA) is a common practice to prevent early arrhythmia recurrence; the data of influence of this practice on longer term ablation outcomes is limited. PURPOSE: The aim of this study was to perform a meta-analysis of published controlled trials comparing temporary AAD therapy after AFA with no AAD therapy in patients after AFA. The primary outcome was recurrence of arrhythmia. RESULTS: 1Eight prospective trials were included. Among 2952 patients, 1991 (67 %) had paroxysmal AF, and 967 (32.7 %) had persistent AF. In total, 1502 patients were treated with AADs and 1450 patients served as a control group (no AAD therapy). Various class IC-III antiarrhythmics were used. Length of AAD administration varied between 6 and 12 weeks after start of AFA. The follow-up duration ranged from 1.5 to 17 months after stopping medication. Among AAD treated patients, the recurrence of arrhythmia rate was 30.69 vs. 33.79 % in control patients (odd ratio 0.86, 95 % CI 0.71-1.06, P = 0.15). In patients who received largely amiodarone, there was a trend for difference in recurrence of atrial arrhythmia (odds ratio 0.60, 95 % CI 0.34-1.09, P = 0.09). CONCLUSIONS: Short-term post pulmonary vein isolation (PVI) AAD therapy does not substantially reduce overall recurrence of AF after ablation. PMID- 27357218 TI - Comparison of Chronic Angioscopic Findings of Bare Metal Stents, 1st-Generation Drug-Eluting Stents and 2nd-Generation Drug-Eluting Stents - Multicenter Study of Intra-Coronary Angioscopy After Stent (MICASA). AB - BACKGROUND: No previous study has reported a comprehensive comparison of the chronic angioscopic findings after bare metal stent (BMS), and 1st- and 2nd generation drug-eluting stents (DES). METHODS AND RESULTS: The Multicenter Study on Intra-Coronary Angioscopy after Stent (MICASA) is a multicenter registry of coronary angioscopy. A total of 264 stents were observed by coronary angioscopy 1 year after PCI. There were 15 BMS, 90 1st-generation DES, and 159 2nd-generation DES. Neointimal coverage (NC) of the stent was classified into 4 grades from 0 (no coverage) to 3 (complete coverage). Yellow color (YC) of plaque at the stented segment was graded from 0 (white) to 3 (bright yellow). Minimum (Min-) and Maximum (Max-) NC grade were significantly lower with 1st- and 2nd-generation DES than with BMS. Although the Max-NC grade was similar, the Min-NC grade was significantly higher for 2nd-generation DES than for 1st-generation DES. Both the YC grade and the incidence of thrombus with 2nd-generation DES were lower than with the 1st-generation DES and were comparable to BMS. Multivariate analysis showed that low-density lipoprotein, 1st-generation DES, and acute coronary syndrome were independent factors for yellow plaque (YG2 or 3), and that hypertension and 1st-generation DES were independent factors for the incidence of thrombus. CONCLUSIONS: Coronary angioscopy revealed more homogeneous coverage with white neointima and less thrombus after 2nd-generation DES as compared with 1st-generation DES. These findings may explain the favorable clinical outcomes observed for patients treated with 2nd-generation DES. (Circ J 2016; 80: 1916 1921). PMID- 27357220 TI - Correction: Mutagenicity of N-acyloxy-N-alkoxyamides as an indicator of DNA intercalation part 1: evidence for naphthalene as a DNA intercalator. AB - Correction for 'Mutagenicity of N-acyloxy-N-alkoxyamides as an indicator of DNA intercalation part 1: evidence for naphthalene as a DNA intercalator' by Tony M. Banks, et al., Org. Biomol. Chem., 2016, 14, 3699-3714. PMID- 27357219 TI - Hemodynamic Analysis of Endoleaks After Endovascular Abdominal Aortic Aneurysm Repair by Using 4-Dimensional Flow-Sensitive Magnetic Resonance Imaging. AB - BACKGROUND: An endoleak is a common complication of endovascular abdominal aortic aneurysm repair (EVAR), and it can be associated with aneurysmal growth. This pilot study used 4-dimensional flow-sensitive magnetic resonance imaging (4D flow) to assess the hemodynamics of different types of endoleaks (I-IV). METHODS AND RESULTS: Magnetic resonance angiography, 4D-flow, and computed tomography angiography (CTA) were performed in 31 patients after nitinol-based stent-graft deployment. With 4D-flow, the 3D streamlines of endoleaks appear as integrated traces along the instantaneous velocity vector field that are color-coded according to the local velocity magnitude of the leak. The 4D-flow analysis identified endoleaks in 18 patients (58.1%), whereas CTA identified endoleaks in 13 patients (41.9%). The 4D-flow analysis created a characteristic image of each type of endoleak. Among patients with endoleaks, 4D-flow identified concomitant multiple endoleaks in 7 (39%) patients, and it further differentiated type II endoleaks from type IIa endoleaks (to-and-fro biphasic flow pattern from a branch vessel) and from type IIb endoleaks (monophasic flow pattern with a connection between the inflow and outflow branches). CONCLUSIONS: The 4D-flow analysis was more sensitive than CTA for detecting an endoleak, and it could subclassify type II endoleaks. In addition, 4D-flow differentiated between concomitant endoleak types in a single patient. (Circ J 2016; 80: 1715-1725). PMID- 27357221 TI - The unexpected case of reactions of halogens and interhalogens with halide substituted Pd(ii) sigma-butadienyl complexes. AB - We have experimentally studied and theoretically interpreted the addition under stoichiometric conditions of halogens or interhalogens to sigma-butadienyl palladium complexes bearing the heteroditopic thioquinolines as spectator ligands. The observed reactions do not involve the expected extrusion of the butadienyl fragment but rather the unpredictable substitution of the halide coordinated to palladium and in some cases also of that bound to the terminal butadienyl carbon. We have explained this peculiar reactivity with a mechanistic hypothesis based on a sequence of selective processes of oxidative addition and reductive elimination involving Pd(iv) intermediates. PMID- 27357222 TI - Trabecular metal tibial knee component still stable at 10 years. AB - Background and purpose - Total knee replacement (TKR) in younger patients using cemented components has shown inferior results, mainly due to aseptic loosening. Excellent clinical results have been reported with components made of trabecular metal (TM). In a previous report, we have shown stabilization of the TM tibial implants for up to 5 years. In this study, we compared the clinical and RSA results of these uncemented implants with those of cemented implants. Patients and methods - 41 patients (47 knees) aged <= 60 years underwent TKR. 22 patients (26 knees) received an uncemented monoblock cruciate-retaining (CR) tibial component (TM) and 19 patients (21 knees) received a cemented NexGen Option CR tibial component. Follow-up examination was done at 10 years, and 16 patients (19 knees) with TM tibial components and 17 patients (18 knees) with cemented tibial components remained for analysis. Results - 1 of 19 TM implants was revised for infection, 2 of 18 cemented components were revised for knee instability, and no revisions were done for loosening. Both types of tibial components migrated in the first 3 months, the TM group to a greater extent than the cemented group. After 3 months, both groups were stable during the next 10 years. Interpretation The patterns of migration for uncemented TM implants and cemented tibial implants over the first 10 years indicate that they have a good long-term prognosis regarding fixation. PMID- 27357224 TI - The joint flanker effect and the joint Simon effect: On the comparability of processes underlying joint compatibility effects. AB - Previous studies observed compatibility effects in different interference paradigms such as the Simon and flanker task even when the task was distributed across two co-actors. In both Simon and flanker tasks, performance is improved in compatible trials relative to incompatible trials if one actor works on the task alone as well as if two co-actors share the task. These findings have been taken to indicate that actors automatically co-represent their co-actor's task. However, recent research on the joint Simon and joint flanker effect suggests alternative non-social interpretations. To which degree both joint effects are driven by the same underlying processes is the question of the present study, and it was scrutinized by manipulating the visibility of the co-actor. While the joint Simon effect was not affected by the visibility of the co-actor, the joint flanker effect was reduced when participants did not see their co-actors but knew where the co-actors were seated. These findings provide further evidence for a spatial interpretation of the joint Simon effect. In contrast to recent claims, however, we propose a new explanation of the joint flanker effect that attributes the effect to an impairment in the focusing of spatial attention contingent on the visibility of the co-actor. PMID- 27357223 TI - Molecular mechanisms in lithium-associated renal disease: a systematic review. AB - PURPOSE: Lithium is an essential treatment in bipolar disorder and treatment resistant depression; however, its use has been limited by concerns regarding its renal adverse effects. An improved understanding of potential molecular mechanisms can help develop prevention and treatment strategies for lithium associated renal disease. METHODS: We conducted a systematic literature search using MEDLINE, Embase, and PsychINFO including English-language original research articles published prior to November 2015 that specifically investigated lithium's effects on nephrogenic diabetes insipidus (NDI) and chronic kidney disease (CKD), using molecular markers. RESULTS: From a total of 3510 records, 71 pre-clinical studies and two relevant clinical studies were identified. Molecular alterations were reported in calcium signaling, inositol monophosphate, extracellular-regulated, prostaglandin, sodium/solute transport, G-protein coupled receptors, nitric oxide, vasopressin/aquaporin, and inflammation-related pathways in lithium-associated renal disease. The majority of studies found that these mechanisms were implicated in NDI, while few studies had examined CKD. DISCUSSION: Future studies will have to focus on (1) validating the present findings in human subjects and (2) examining CKD, which is the most clinically relevant lithium-associated renal effect. This will improve our understanding of lithium's biological effects, as well as inform a personalized medicine approach, which could lead to safer lithium prescribing and less renal adverse events. PMID- 27357225 TI - Isolation and characterization of Enterobacteriaceae species infesting post harvest strawberries and their biological control using bacteriophages. AB - Strawberry is a significantly consumed fruit worldwide, mostly without being subjected to disinfection processes. During the harvest and transfer from farm to consumers as well as where organic farming practises have been employed, the surface of the fruit may become contaminated by pathogenic bacteria. Post-harvest strawberry fruits in punnets available for public consumption were thus screened for the presence of enteric bacteria in the Sunshine Coast region of Queensland, Australia. Some of the tested samples (13 %) were found to carry such bacteria and even in greater numbers if organic amendments were used (69 %). The bacteria were found to belong in the genera of Escherichia, Enterobacter, Raoultella, Klebsiella, Pantoea, Shigella, Citrobacter and Cronobacter within the family Enterobacteriaceae. Some of the isolates were found to adhere to Caco-2 cells representing human gut epithelium as well as carrying virulence and toxin genes. Resistance mostly against sulphafurazole, cefoxitin, ampicillin and nitrofurantoin was found among 14 different antimicrobial agents tested including 100 % resistance to cefoxitin and ampicillin in the genus Pantoea. In the second phase of the study, bacteriophages were isolated against the isolates and were subsequently applied to post-harvest fruits. A significant (P <= 0.001) reduction in the number of enteric bacteria was observed when a high-titre polyvalent bacteriophage suspension (*10(12) PFU/mL) was applied to the fruit surface. Bacteriophages also decreased the adhesion of the Escherichia coli isolates to Caco-2 cells. Findings might indicate that biological control using bacteriophages might be of significant value for the industry targeting to reduce pathogenic loads of bacteria on the fruit. PMID- 27357226 TI - Candida utilis and Cyberlindnera (Pichia) jadinii: yeast relatives with expanding applications. AB - The yeast Candida utilis is used as a food additive and as a host for heterologous gene expression to produce various metabolites and proteins. Reliable protocols for intracellular production of recombinant proteins are available for C. utilis and have now been expanded to secrete proteins into the growth medium or to achieve surface display by linkage to a cell wall protein. A recombinant C. utilis strain was recently shown to induce oral tolerance in a mouse model of multiple sclerosis suggesting future applications in autoimmune therapy. Whole genome sequencing of C. utilis and its presumed parent Cyberlindnera (Pichia) jadinii demonstrated different ploidy but high sequence identity, consistent with identical recombinant technologies for both yeasts. C. jadinii was recently described as an antagonist to the important human fungal pathogen Candida albicans suggesting its use as a probiotic agent. The review summarizes the status of recombinant protein production in C. utilis, as well as current and future biotechnological and medical applications of C. utilis and C. jadinii. PMID- 27357227 TI - Target genes of the Streptomyces tsukubaensis FkbN regulator include most of the tacrolimus biosynthesis genes, a phosphopantetheinyl transferase and other PKS genes. AB - Tacrolimus (FK506) is a 23-membered macrolide immunosuppressant used in current clinics. Understanding how the tacrolimus biosynthetic gene cluster is regulated is important to increase its industrial production. Here, we analysed the effect of the disruption of fkbN (encoding a LAL-type positive transcriptional regulator) on the whole transcriptome of the tacrolimus producer Streptomyces tsukubaensis using microarray technology. Transcription of fkbN in the wild type strain increases from 70 h of cultivation reaching a maximum at 89 h, prior to the onset of tacrolimus biosynthesis. Disruption of fkbN in S. tsukubaensis does not affect growth but prevents tacrolimus biosynthesis. Inactivation of fkbN reduces the transcription of most of the fkb cluster genes, including some all (for allylmalonyl-CoA biosynthesis) genes but does not affect expression of allMNPOS or fkbR (encoding a LysR-type regulator). Disruption of fkbN does not suppress transcription of the cistron tcs6-fkbQ-fkbN; thus, FkbN self-regulates only weakly its own expression. Interestingly, inactivation of FkbN downregulates the transcription of a 4'-phosphopantetheinyl transferase coding gene, which product is involved in tacrolimus biosynthesis, and upregulates the transcription of a gene cluster containing a cpkA orthologous gene, which encodes a PKS involved in coelimycin P1 biosynthesis in Streptomyces coelicolor. We propose an information theory-based model for FkbN binding sequences. The consensus FkbN binding sequence consists of 14 nucleotides with dyad symmetry containing two conserved inverted repeats of 7 nt each. This FkbN target sequence is present in the promoters of FkbN-regulated genes. PMID- 27357228 TI - C1 fractures: a review of diagnoses, management options, and outcomes. AB - The atlas is subject to fracture under axial load, often due to traumatic injuries such as shallow dives and automobile accidents. These fractures account for 2-13 % of injuries to the cervical spine [Marcon RM et al. Clinics (Sao Paulo) 68(11):1455-61, 2013]. Fractures of the C1 vertebra are often difficult to diagnose, as there is often no neurological deficit or easily identifiable findings on radiographs. However, injuries to the atlas can be associated with vertebral artery injury and atlantoaxial or atlanto-occipital instability, making prompt and accurate diagnosis imperative. A detailed understanding of the anatomy, inherent stability, and common injury patterns is essential for any surgeon treating spinal trauma. This chapter explores the diagnosis and management of C1 fractures, as well as outcomes after treatment. PMID- 27357229 TI - Whole blood for the acutely haemorrhaging civilian trauma patient: a novel idea or rediscovery? AB - The concept of whole blood (WB) as a treatment modality for trauma patients requiring transfusion therapy is not new. Successfully employed in the early 20 century, WB was the product of choice for military trauma resuscitation until the advent of component therapy changed the landscape of transfusion medicine. However, the recognition of the success of WB in the military operational setting has provided some enthusiasm to explore its revival as a cold-stored option in the civilian trauma resuscitation sector. Concerns continue to exist over potential limitations for its application in regards to the efficacy of platelets after cold storage, the risk of haemolytic transfusion reactions following the transfusion of un-cross-matched WB and the logistical issues for civilian blood banks in providing WB. This review aims to reconcile these concerns with data available in the literature, with a view to establishing that there is in vitro evidence supporting the haemostatic effects of cold-stored WB as a potential therapeutic option in both the pre-hospital and in-hospital civilian trauma resuscitation settings. PMID- 27357230 TI - Temporal tuning in the bat auditory cortex is sharper when studied with natural echolocation sequences. AB - Precise temporal coding is necessary for proper acoustic analysis. However, at cortical level, forward suppression appears to limit the ability of neurons to extract temporal information from natural sound sequences. Here we studied how temporal processing can be maintained in the bats' cortex in the presence of suppression evoked by natural echolocation streams that are relevant to the bats' behavior. We show that cortical neurons tuned to target-distance actually profit from forward suppression induced by natural echolocation sequences. These neurons can more precisely extract target distance information when they are stimulated with natural echolocation sequences than during stimulation with isolated call echo pairs. We conclude that forward suppression does for time domain tuning what lateral inhibition does for selectivity forms such as auditory frequency tuning and visual orientation tuning. When talking about cortical processing, suppression should be seen as a mechanistic tool rather than a limiting element. PMID- 27357231 TI - The LXR ligand GW3965 inhibits Newcastle disease virus infection by affecting cholesterol homeostasis. AB - Newcastle disease (ND) is a contagious disease that affects most species of birds. Its causative pathogen, Newcastle disease virus (NDV), also exhibits considerable oncolytic activity against mammalian cancers. A better understanding of the pathogenesis of NDV will help us design efficient vaccines and novel anticancer strategies. GW3965, a widely used synthetic ligand of liver X receptor (LXR), induces the expression of LXRs and its downstream genes, including ATP binding cassette transporter A1 (ABCA1). ABCA1 regulates cellular cholesterol homeostasis. Here, we found that GW3965 inhibited NDV infection in DF-1 cells. It also inhibited NF-kappaB activation and reduced the upregulation of proinflammatory cytokines induced by the infection. Further studies showed that GW3965 exerted its inhibitory effects on virus entry and replication. NDV infection increased the mRNA levels of several lipogenic genes but decreased the ABCA1 mRNA level. Overexpression of ABCA1 inhibited NDV infection and reduced the cholesterol content in DF-1 cells, but when the cholesterol was replenished, NDV infection was restored. GW3965 treatment prevented cholesterol accumulation in the perinuclear area of the infected cells. In summary, our studies suggest that GW3965 inhibits NDV infection, probably by affecting cholesterol homeostasis. PMID- 27357233 TI - The entire mean weighted first-passage time on a family of weighted treelike networks. AB - In this paper, we consider the entire mean weighted first-passage time (EMWFPT) with random walks on a family of weighted treelike networks. The EMWFPT on weighted networks is proposed for the first time in the literatures. The dominating terms of the EMWFPT obtained by the following two methods are coincident. On the one hand, using the construction algorithm, we calculate the receiving and sending times for the central node to obtain the asymptotic behavior of the EMWFPT. On the other hand, applying the relationship equation between the EMWFPT and the average weighted shortest path, we also obtain the asymptotic behavior of the EMWFPT. The obtained results show that the effective resistance is equal to the weighted shortest path between two nodes. And the dominating term of the EMWFPT scales linearly with network size in large network. PMID- 27357232 TI - Genome-wide transcriptome analysis of female-sterile rice ovule shed light on its abortive mechanism. AB - MAIN CONCLUSION: The comprehensive transcriptome analysis of rice female-sterile line and wild-type line ovule provides an important clue for exploring the regulatory network of the formation of rice fertile female gametophyte. Ovules are the female reproductive tissues of rice (Oryza sativa L.) and play a major role in sexual reproduction. To investigate the potential mechanism of rice female gametophyte fertility, we used RNA sequencing, combined with genetic subtraction, to compare the transcriptome of the ovules of a high-frequency female-sterile line (fsv1) and a rice wild-type line (Gui 99) during ovule development. Ovules were harvested at three developmental stages: ovule containing megaspore mother cell in meiosis process (stage 1), ovule containing functional megaspore in mitosis process (stage 2), and ovule containing mature female gametophyte (stage 3). Six cDNA libraries generated a total of 42.2 million high-quality clean reads that aligned with 30,204 genes. The comparison between the fsv1 and Gui 99 ovules identified a large number of differentially expressed genes (DEGs), i.e., 45, 495, and 932 DEGs at the three ovule developmental stages, respectively. From the comparison of the two rice lines, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and MapMan analyses indicated that a large number of DEGs associated with starch and sucrose metabolism, plant hormone signal transduction, protein modification and degradation, oxidative phosphorylation, and receptor kinase. These DEGs might play roles in ovule development and fertile female gametophyte formation. Many transcription factor genes and epigenetic-related genes also exhibit different expression patterns and significantly different expression levels in two rice lines during ovule development, which might provide important information regarding the abortive mechanism of the female gametophyte in rice. PMID- 27357234 TI - Experimental and theoretical studies on the linear and nonlinear optical properties of lead phosphate crystals LiPbPO4. AB - Phosphates with noncentrosymmetric (NCS) structures usually display short ultraviolet (UV) cut-off edges, but often exhibit weak powder second harmonic generation (SHG) intensities. Here we synthesized a NCS-phosphate, LiPbPO4, that achieves a desired balance between UV transparency, a cut-off edge of about 232 nm, and large SHG activity (about 3 * KDP). The three dimensional (3D) framework of LiPbPO4 consists of PO4 and LiO4 tetrahedra that are corner-shared, forming wide channels where lead cations reside. Local dipole moments for the PO4 and LiO4 tetrahedra as well as lead polyhedra in a unit cell were calculated. First principles calculations have been performed for better understanding the structure-property relationships in LiPbPO4. In addition, to further explore spatial distribution of the electronic states dominating the NLO activity, the SHG density method was employed. PMID- 27357236 TI - The impact of environmental conditions on Campylobacter jejuni survival in broiler faeces and litter. AB - INTRODUCTION: Campylobacter jejuni is the leading bacterial food-borne pathogen within the European Union, and poultry meat is an important vehicle for its transmission to humans. However, there is limited knowledge about how this organism persists in broiler litter and faeces. The aim of this study was to assess the impact of a number of environmental parameters, such as temperature, humidity, and oxygen, on Campylobacter survival in both broiler litter and faeces. MATERIALS AND METHODS: Used litter was collected from a Campylobacter negative broiler house after final depopulation and fresh faeces were collected from transport crates. Samples were confirmed as Campylobacter negative according to modified ISO methods for veterinary samples. Both sample matrices were inoculated with 9 log10 CFU/ml C. jejuni and incubated under high (>=85%) and low (<=70%) relative humidity conditions at three different temperatures (20 degrees C, 25 degrees C, and 30 degrees C) under both aerobic and microaerophilic atmospheres. Inoculated litter samples were then tested for Campylobacter concentrations at time zero and every 2 hours for 12 hours, while faecal samples were examined at time zero and every 24 hours for 120 hours. A two-tailed t-test assuming unequal variance was used to compare mean Campylobacter concentrations in samples under the various temperature, humidity, and atmospheric conditions. RESULTS AND DISCUSSION: C. jejuni survived significantly longer (P<=0.01) in faeces, with a minimum survival time of 48 hours, compared with 4 hours in used broiler litter. C. jejuni survival was significantly enhanced at 20 degrees C in all environmental conditions in both sample matrices tested compared with survival at 25 degrees C and 30 degrees C. In general, survival was greater in microaerophilic compared with aerobic conditions in both sample matrices. Humidity, at the levels examined, did not appear to significantly impact C. jejuni survival in any sample matrix. The persistence of Campylobacter in broiler litter and faeces under various environmental conditions has implications for farm litter management, hygiene, and disinfection practices. PMID- 27357235 TI - IL-13 from intraepithelial lymphocytes regulates tissue homeostasis and protects against carcinogenesis in the skin. AB - The skin is under constant renewal and exposure to environmental challenges. How homeostasis is maintained alongside protective mechanisms against damage is unclear. Among the basal epithelial cells (ECs) is a population of resident intraepithelial lymphocytes (IELs) that provide host-protective immune surveillance. Here we show that IELs cross-communicate with ECs via the production of IL-13. Skin ECs are activated by IEL-derived IL-13, enabling a canonical EC stress response. In the absence of IL-13, or canonical IEL, the skin has decreased ability to repair its barrier and increased susceptibility to cutaneous carcinogenesis. IL-13 controls the rate of EC movement through the epidermis, which might explain the importance of IL-13 for epidermal integrity and its suppressive effect on skin carcinogenesis. These findings show that IL-13 acts as a molecular bridge between IELs and ECs, and reveal a critical host defensive role for type-2 immunity in regulating EC tissue homeostasis and carcinogenesis. PMID- 27357237 TI - Turnover of Village Chickens Undermines Vaccine Coverage to Control HPAI H5N1. AB - Highly pathogenic avian influenza (HPAI) subtype H5N1 remains an enzootic disease of village chickens in Indonesia, posing ongoing risk at the animal-human interface. Previous modelling showed that the fast natural turnover of chicken populations might undermine herd immunity after vaccination, although actual details of how this effect applies to Indonesia's village chicken population have not been determined. We explored the turnover effect in Indonesia's scavenging and mixed populations of village chickens using an extended Leslie matrix model parameterized with data collected from village chicken flocks in Java region, Indonesia. Population dynamics were simulated for 208 weeks; the turnover effect was simulated for 16 weeks after vaccination in two 'best case' scenarios, where the whole population (scenario 1), or birds aged over 14 days (scenario 2), were vaccinated. We found that the scavenging and mixed populations have different productive traits. When steady-state dynamics are reached, both populations are dominated by females (54.5%), and 'growers' and 'chicks' represent the most abundant age stages with 39% and 38% in the scavenging, and 60% and 25% in the mixed population, respectively. Simulations showed that the population turnover might reduce the herd immunity below the critical threshold that prevents the re emergence of HPAI H5N1 4-8 weeks (scavenging) and 6-9 weeks (mixed population) after vaccination in scenario 1, and 2-6 weeks (scavenging) and 4-7 weeks (mixed population) after vaccination in scenario 2. In conclusion, we found that Indonesia's village chicken population does not have a unique underlying population dynamic and therefore, different turnover effects on herd immunity may be expected after vaccination; nonetheless, our simulations carried out in best case scenarios highlight the limitations of current vaccine technologies to control HPAI H5N1. This suggests that the improvements and complementary strategies are necessary and must be explored. PMID- 27357238 TI - Elderly men in Tokyo homeless shelters who are suspected of having cognitive impairment. PMID- 27357239 TI - Dual electrically and thermally responsive broadband reflectors based on polymer network stabilized chiral nematic liquid crystals: the role of crosslink density. AB - A broadband reflector based on a polymer stabilized chiral nematic liquid crystal has been fabricated. The reflection bandwidth can be manually controlled by an electric field and autonomously by temperature. PMID- 27357240 TI - Using modeling and rehearsal to teach fire safety to children with autism. AB - We evaluated the efficacy of an instructional procedure to teach young children with autism to evacuate settings and notify an adult during a fire alarm. A multiple baseline design across children showed that an intervention that included modeling, rehearsal, and praise was effective in teaching fire safety skills. Safety skills generalized to novel settings and maintained during a 5 week follow-up in both training and generalization settings. PMID- 27357241 TI - Persistent Diarrhea: A Clinical Review. AB - IMPORTANCE: Diarrheal disease is commonly encountered in clinical practice. Persistent diarrhea (>=14 days) can be caused by pathogens that differ from those commonly seen in acute illness; proper etiologic diagnosis is important for appropriate therapeutic management. This review provides an overview of the epidemiology, etiology, diagnosis, and management of persistent diarrhea caused by infectious agents in immunocompetent individuals worldwide. OBSERVATIONS: Much of the data on persistent diarrhea comes from studies of residents in or expatriates of developing countries and travelers to these regions where follow up studies have been performed. Persistent diarrhea occurs in approximately 3% of individuals traveling to developing countries. Schistosoma mansoni (and rarely Schistosoma haematobium) intestinal infection is also not very common and is found only in endemic areas. The microbiologic causes of protracted diarrhea include detectable parasitic (eg, Giardia, Cryptosporidium) and bacterial (eg, enteroaggregative Escherichia coli, Shigella) pathogens. Available diagnostic tests include culture-dependent for bacterial pathogens and culture-independent methods for bacterial, viral, and protozoal infections (eg, polymerase chain reaction [PCR]), including multiplex PCR, as well as and microscopy for protozoal infections. Antimicrobial therapy can be given empirically to patients returning from the undeveloped to the developed world. Otherwise, antibiotics should be given based on the results of laboratory testing. CONCLUSIONS AND RELEVANCE: Persistent diarrhea is a poorly recognized syndrome in all populations that requires proper assessment and diagnosis to ensure that affected individuals receive the treatment needed to experience improvement of clinical symptoms. PMID- 27357242 TI - Urinalysis in the Evaluation of Hematuria. PMID- 27357243 TI - Lipidomic Signatures and Associated Transcriptomic Profiles of Clear Cell Renal Cell Carcinoma. AB - Renal cell carcinoma (RCC) is the most common histological type of adult kidney cancer. In this study, we obtained lipidomic profiles of clear cell RCC (ccRCC), a major RCC subtype, by performing a lipidomic analysis of specimens of cancerous tissue and the surrounding normal renal cortex obtained from the same patients (N = 49). We also compared the lipidomic profiles with the lipogenic transcriptome of specimens of cancerous tissue and the surrounding normal renal cortex for an additional set of patient samples (N = 95). Overall, we detected 326 lipids, including phospholipids, sphingolipids, neutral lipids, and eicosanoids. The levels of more than 70% of the detected lipids were significantly different (P < 0.01, corrected by the false discovery rate). The cancerous tissue was distinguished by higher levels of ether-type phospholipids, cholesterol esters, and triacylglycerols, as well as by lower levels of phospholipids (except for phosphatidylcholines) and polyunsaturated fatty acids. Characteristic changes in the levels of mRNAs and metabolites suggested that the phosphatidylethanolamine (PE) synthesis pathway is suppressed in ccRCC and associated with cell proliferation. The present study represents the lipidomic profiles of ccRCC, which provides novel information about the metabolic changes in renal cancerous tissue and RCC pathophysiology. PMID- 27357244 TI - Structure and Function of Four Classes of the 4Fe-4S Protein, IspH. AB - IspH, (E)-1-hydroxy-2-methyl-but-2-enyl 4-diphosphate reductase, is an essential enzyme in isoprenoid biosynthesis and an important drug/herbicide target. Using X ray crystallographic, bioinformatics, mutagenesis/kinetics/stability, and electron paramagnetic resonance (EPR) results, we show that organisms from different environments ultilize one of four main IspH classes. The classes are based on the arrangement of the aromatic residues near the 4Fe-4S cluster and the presence or absence of N- and C-terminal extensions. Class A enzymes are found primarily in anaerobic and microaerophilic bacteria. Class B enzymes are found in aerobic bacteria. Class C enzymes are found in cyanobacteria and plants. Class D enzymes are found in apicomplexan parasites. Using mutagenesis, we show that the cluster-associated aromatic groups in class A and class B IspHs enhance cluster oxidative stability. Y198A, F302A, and a C-terminal truncation mutant of the class B (Escherichia coli) IspH have catalytic activity lower than that of the wild-type protein when using methyl viologen as the electron donor, but higher activity with dithionite as the electron donor, due to ready access of the small reductant to the cluster, consistent with their increased oxygen and H2O2 sensitivity. F302A has the largest effect on the reaction rates, and EPR studies indicate this residue affects Fe-S cluster structure. Similar effects on cluster stability are seen with class A (F14A and Y98A) mutants; however, effects on ET rates are smaller, and there are no differences between the EPR spectra of mutant and wild-type proteins. Overall, the results are of general interest because they show, for the first time, that there are multiple IspH classes that have evolved to allow organisms to survive in diverse oxidative-stress environments. PMID- 27357245 TI - Predictors of the 10-year direct costs for treating multiple sclerosis. AB - OBJECTIVES: Disease-modifying treatments (DMTs) constitute the largest direct medical cost for multiple sclerosis (MS). This study aims at investigating predictors of the 10-year economic burden for DMT administration and management. MATERIALS AND METHODS: This study included 537 newly diagnosed, drug naive relapsing-remitting MS (RRMS) patients, followed up for 10.1+/-3.3 years. Costs for DMT administration and management were calculated, and referred to each year of observation (annual costs). Possible predictors of disease evolution were categorized into early predictors (age, gender, disease duration, baseline expanded disability status scale (EDSS), 1-point EDSS progression within 2 years, and annualized relapse rate -ARR- within 2 years), and long-term predictors (reaching of EDSS 4.0, conversion to secondary progressive -SP-, ARR, number of DMTs, follow-up duration). Association between predictors and study outcome was explored using mixed-effects log-linear regression models. RESULTS: A 1-point higher EDSS at diagnosis was associated with 13.21% increase in the annual costs (95%CI=4.16-23.04%). Each additional year of age at diagnosis was associated with a 0.74% decrease in the annual costs (95%CI=-1.43 to-0.04%). Female gender was associated with a 12.43% decrease in the annual costs (95%CI=-22.61 to-0.93%). Converting to SP was associated with a 14.26% decrease in the annual costs (95%CI=-14.26 to-2.94%). Each additional year of follow-up was associated with a 3.05% decrease in the annual costs (95%CI=-4.51 to-1.57%). CONCLUSIONS: An estimate of the 10-year costs associated with DMT administration and management can be calculated by analyzing different factors, and might be of particular interest for planning resources needed for treating people with MS. PMID- 27357246 TI - Polar interface phonons in ionic toroidal systems. AB - We use the dielectric continuum model to obtain the polar (Fuchs-Kliewer like) interface vibration modes of toroids made of ionic materials either embedded in a different material or in vacuum, with applications to nanotoroids specially in mind. We report the frequencies of these modes and describe the electric potential they produce. We establish the quantum-mechanical Hamiltonian appropriate for their interaction with electric charges. This Hamiltonian can be used to describe the effect of this interaction on different types of charged particles either inside or outside the torus. PMID- 27357247 TI - Accuracy of methods to measure femoral head penetration within metal-backed acetabular components. AB - A number of different software programs are used to investigate the in vivo wear of polyethylene bearings in total hip arthroplasty. With wear rates below 0.1 mm/year now commonly being reported for highly cross-linked polyethylene (XLPE) components, it is important to identify the accuracy of the methods used to measure such small movements. The aims of this study were to compare the accuracy of current software programs used to measure two-dimensional (2D) femoral head penetration (FHP) and to determine whether the accuracy is influenced by larger femoral heads or by different methods of representing the acetabular component within radiostereometric analysis (RSA). A hip phantom was used to compare known movements of the femoral head within a metal-backed acetabular component to FHP measured radiographically using RSA, Hip Analysis Suite (HAS), PolyWare, Ein Bild Roentgen Analyse (EBRA), and Roentgen Monographic Analysis Tool (ROMAN). RSA was significantly more accurate than the HAS, PolyWare, and ROMAN methods when measuring 2D FHP with a 28 mm femoral head. Femoral head size influenced the accuracy of HAS and ROMAN 2D FHP measurements, EBRA proximal measurements, and RSA measurements in the proximal and anterior direction. The use of different acetabular reference segments did not influence accuracy of RSA measurements. The superior accuracy and reduced variability of RSA wear measurements allow much smaller cohorts to be used in RSA clinical wear studies than those utilizing other software programs. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:988-996, 2017. PMID- 27357249 TI - Bufalin reverses intrinsic and acquired drug resistance to cisplatin through the AKT signaling pathway in gastric cancer cells. AB - Cisplatin is the most common chemotherapeutic agent for gastric cancer (GC), however it activates AKT, which contributes to intrinsic and acquired resistance. Bufalin, a traditional Chinese medicine, shows significant anticancer activity by inhibiting the AKT pathway. It was therefore hypothesized that bufalin could counteract cisplatin resistance in GC cells. SGC7901, MKN-45 and BGC823 human GC cells were cultured under normoxic and hypoxic conditions. Effects of cisplatin and bufalin on GC cells were measured by a cell counting kit, apoptosis was analyzed by flow cytometry, and immunoblotting was used to detect proteins associated with the AKT signaling pathway. It was demonstrated that bufalin synergized with cisplatin to inhibit proliferation and promote apoptosis of GC cells by diminishing the activation of cisplatin-induced AKT under normoxic and hypoxic conditions. Bufalin also inhibits cisplatin-activated molecules downstream of AKT that affect proliferation and apoptosis, including glycogen synthase kinase, mammalian target of rapamycin, ribosomal protein S6 Kinase and eukaryotic translation initiation factor-4E-binding protein-1. To investigate acquired cisplatin resistance, a cisplatin-resistant cell line SGC7901-CR was used. It was demonstrated that bufalin reversed acquired cisplatin resistance and significantly induced apoptosis through the AKT pathway. These results imply that bufalin could extend the therapeutic effect of cisplatin on GC cells when administered in combination. PMID- 27357248 TI - Intrinsic FGF2 and FGF5 promotes angiogenesis of human aortic endothelial cells in 3D microfluidic angiogenesis system. AB - The human body contains different endothelial cell types and differences in their angiogenic potential are poorly understood. We compared the functional angiogenic ability of human aortic endothelial cells (HAECs) and human umbilical vein endothelial cells (HUVECs) using a three-dimensional (3D) microfluidic cell culture system. HAECs and HUVECs exhibited similar cellular characteristics in a 2D culture system; however, in the 3D microfluidic angiogenesis system, HAECs exhibited stronger angiogenic potential than HUVECs. Interestingly, the expression level of fibroblast growth factor (FGF)2 and FGF5 under vascular endothelial growth factor (VEGF)-A stimulation was significantly higher in HAECs than in HUVECs. Moreover, small interfering RNA-mediated knockdown of FGF2 and FGF5 more significantly attenuated vascular sprouting induced from HAECs than HUVECs. Our results suggest that HAECs have greater angiogenic potential through FGF2 and FGF5 upregulation and could be a compatible endothelial cell type to achieve robust angiogenesis. PMID- 27357250 TI - [Claims following "malpractice" : Who is how often affected?]. PMID- 27357251 TI - [Hemolytic kidney failure and transient ischemic attack in a 32-year-old female]. AB - We report on the case of a 32-year-old female patient who initially presented with oliguric acute renal failure, hemolytic anemia with moderate thrombocytopenia and subsequently developed a transient ischemic attack in the cerebellum. The kidney biopsy revealed clinically suspected atypical hemolytic uremic syndrome (aHUS), which was confirmed by intraglomerular thrombotic microangiopathy (TMA). Treatment with plasmapheresis and sustained administration of the C5 inhibitor eculizumab resulted in hematological remission but without improvement of kidney function. Further etiological investigations led to reduced plasma levels of inhibitory complement factor I on the basis of a heterozygous CFI mutation. In patients with aHUS molecular genetic investigations are indicated in order to determine the underlying cause, to regulate the therapeutic regimen and to allow prognostic statements with respect to a potential kidney transplantation. PMID- 27357252 TI - Multilocus sequence typing and CTX-M characterization of ESBL-producing E. coli: a prospective single-centre study in Lower Saxony, Germany. AB - The increasing prevalence of extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria is a serious threat for current healthcare settings. In this study we investigated the molecular epidemiology of ESBL-producing E. coli at the University Medical Center Gottingen in Lower Saxony, Germany. All E. coli isolates with an ESBL phenotype were collected during a 6-month period in 2014. Multilocus sequence typing and CTX-M characterization were performed on 160 isolates. Of the ESBL-producing isolates 95.6% were CTX-M positive. Compared to recent Germany-wide studies, we found CTX-M-1 to occur in higher frequency than CTX-M-15 (44.4% vs. 34.4%). CTX-M-14 and CTX-M-27 were detected at 9.4% and 5.0%, respectively. The globally dominant sequence type (ST) 131, which is often associated with CTX-M-15, occurred at a relatively low rate of 24%. Major non ST131 sequence types were ST101 (5%), ST58 (5%), ST10 (4.4%), ST38 (4.4%), ST410 (3.8%) and ST453 (3.1%). Several of these major sequence types were previously shown to be associated with livestock farming. Together, our study indicates that E. coli lineage distribution in individual healthcare settings can significantly differ from average numbers obtained in nationwide studies. PMID- 27357253 TI - Sinus Floor Cortication: Classification and Prevalence. AB - PURPOSE: To present a classification and assess the presence and degree of cortication of the sinus floor utilizing Computerized Tomography (CT) scan images. MATERIALS AND METHODS: One hundred CT scans, of patient who required a sinus augmentation procedure (SAP), were evaluated and classified according to the Type of sinus floor cortication (SFC). Type 1: sinus floor showing similar or higher density than the surrounding cortical areas. Type 2: sinus floor showing less density than the surrounding cortical areas. Type 3: sinus floor showing no cortical bone. Type 4: sinus floor showing the fusion of sinus floor bone and native crestal bone. RESULTS: The SFC were present in 31, 41, 18, and 10 cases in Type 1, 2, 3, and 4, respectively. CONCLUSIONS: This classification based on the level of cortication of the sinus floor is clinically useful as a method of determining if the dental implant can be placed simultaneously or not with the SAP, or can be placed even without a SAP. PMID- 27357254 TI - Autoimmunity: Do IgM antibodies protect against atherosclerosis in SLE? PMID- 27357255 TI - Spondyloarthropathies: CVD prevention and statin therapy in ankylosing spondylitis. PMID- 27357256 TI - Connective tissue diseases: OX40L inhibition blocks tissue fibrosis. PMID- 27357257 TI - Pathogenesis of bronchopulmonary dysplasia: when inflammation meets organ development. AB - Bronchopulmonary dysplasia is a chronic lung disease of preterm infants. It is caused by the disturbance of physiologic lung development mainly in the saccular stage with lifelong restrictions of pulmonary function and an increased risk of abnormal somatic and psychomotor development. The contributors to this disease's entity are multifactorial with pre- and postnatal origin. Central to the pathogenesis of bronchopulmonary is the induction of a massive pulmonary inflammatory response due to mechanical ventilation and oxygen toxicity. The extent of the pro-inflammatory reaction and the disturbance of further alveolar growth and vasculogenesis vary largely and can be modified by prenatal infections, antenatal steroids, and surfactant application.This minireview summarizes the important recent research findings on the pulmonary inflammatory reaction obtained in patient cohorts and in experimental models. Unfortunately, recent changes in clinical practice based on these findings had only limited impact on the incidence of bronchopulmonary dysplasia. PMID- 27357259 TI - Evidence of cardiac injury and arrhythmias in dogs with acute kidney injury. AB - OBJECTIVES: Cardiac involvement in the course of acute kidney injury is described in humans as cardiorenal syndrome type 3 but has received only limited attention in dogs. This study was designed to evaluate cardiac injury and dysfunction in acute kidney injury in dogs and its association with outcome. METHODS: This prospective cohort study enrolled 24 client-owned dogs with acute kidney injury. Cardiac disorders were evaluated with thoracic radiographs, echocardiography, 24 hour Holter monitoring and cardiac troponin I concentrations within 2 days of admission and 7 to 10 days later. RESULTS: Most dogs were diagnosed with leptospirosis (n=18, 75%) and presented with moderate-to-severe acute kidney injury, International Renal Interest Society grades III to V. Dogs with e100 ventricular premature complexes per 24 hour in the first examination (n=8) had significantly higher initial cTnI concentrations (P=0.007) compared to dogs with fewer than 100. In receiver operating characteristic curve analysis, the number of ventricular premature complexes was predictive of outcome (AUC 0.83, P<0.001). CLINICAL SIGNIFICANCE: Acute kidney injury seems to be associated with cardiac injury and arrhythmias in dogs. The data do not indicate a cardiac cause of poor outcome in dogs with increased number of ventricular premature complexes but the association may reflect the severity of disease. PMID- 27357260 TI - Multifunctional, Highly Flexible, Free-Standing 3D Polypyrrole Foam. AB - Multifunctional, highly flexible 3D polypyrrole (PPy) foam is fabricated via a simple electrodeposition method by using nickel foam as the template. The 3D PPy foam has a unique interior structure and is robust enough to manipulate directly. PMID- 27357258 TI - Cold acclimation wholly reorganizes the Drosophila melanogaster transcriptome and metabolome. AB - Cold tolerance is a key determinant of insect distribution and abundance, and thermal acclimation can strongly influence organismal stress tolerance phenotypes, particularly in small ectotherms like Drosophila. However, there is limited understanding of the molecular and biochemical mechanisms that confer such impressive plasticity. Here, we use high-throughput mRNA sequencing (RNA seq) and liquid chromatography - mass spectrometry (LC-MS) to compare the transcriptomes and metabolomes of D. melanogaster acclimated as adults to warm (rearing) (21.5 degrees C) or cold conditions (6 degrees C). Cold acclimation improved cold tolerance and led to extensive biological reorganization: almost one third of the transcriptome and nearly half of the metabolome were differentially regulated. There was overlap in the metabolic pathways identified via transcriptomics and metabolomics, with proline and glutathione metabolism being the most strongly-supported metabolic pathways associated with increased cold tolerance. We discuss several new targets in the study of insect cold tolerance (e.g. dopamine signaling and Na(+)-driven transport), but many previously identified candidate genes and pathways (e.g. heat shock proteins, Ca(2+) signaling, and ROS detoxification) were also identified in the present study, and our results are thus consistent with and extend the current understanding of the mechanisms of insect chilling tolerance. PMID- 27357261 TI - Association between self-reported bupropion use and glaucoma: a population-based study. AB - PURPOSE: To investigate the relationship between self-reported bupropion use and self-reported glaucoma in a nationally representative sample of the US population. METHODS: This cross-sectional study included 6760 participants in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2008, age >=40 years, who responded to a question regarding their glaucoma status. Participants were interviewed regarding the use of prescription medications, and those ascertained as having used bupropion were further divided into groups based on duration of usage. Other relevant information, including demographics, comorbidities and health-related behaviours, was obtained via interview. Multivariate logistic regression was performed to determine the OR and 95% CIs for association between bupropion use and prevalent glaucoma. Covariates in the final multivariate model included parameters associated with glaucoma at p<0.1: age, gender, ethnicity and annual income. RESULTS: 453 participants self-reported a diagnosis of glaucoma, and 108 reported bupropion medication use. Participants who reported using bupropion for more than 1 year had decreased odds of self reporting a diagnosis of glaucoma (unadjusted OR=0.5, 95% CI 0.01 to 0.52; adjusted OR=0.1, 95% CI 0.01 to 0.81) compared with those not using bupropion or using it for less than a year. CONCLUSIONS: Bupropion use, particularly for an extended period of time, may be associated with a reduced risk of glaucomatous disease. PMID- 27357262 TI - Trends in patterns of antidepressant use in older general population between 2006 and 2012 following publication of practice guidelines. AB - OBJECTIVE: The French regulatory agency published in 2006 practice guidelines related to the management of depressive and anxiety disorders. The main objective of the study was to assess their impact regarding use and monitoring of antidepressant drug treatment in older patients. The secondary objective was to identify factors associated with compliance with practice guidelines. METHODS: A historical fixed cohort study with dynamic follow-up time was conducted in 16,144 subjects aged 65 years and over, initiating antidepressant treatment and registered in the National Health Insurance Database between 2006 and 2012. Compliance with guidelines was assessed from year to year using segmented regression analysis. Multiple logistic regressions were used to identify factors associated with compliance with guidelines. RESULTS: Duration of antidepressant treatment was compliant with guidelines in 13.0% of patients aged 65-74 years and 18.5% of patients aged 75 years and over. Biological monitoring was performed in 12.6% of patients aged 65-74 years and 18.5% of patients aged 75 years and over. No significant change of rate of compliance with guidelines was observed over the study period. Compliance of prescriptions with guidelines was associated with patient's age, specialty of the prescriber, presence of chronic disease, year of treatment initiation, and presence of a university hospital in the area of residence. CONCLUSION: While treatment duration and biological monitoring were often inadequate in older patients, the publication of guidelines by the French health regulatory authorities did not lead to any significant and sustained improvement in their patterns of antidepressant use. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27357263 TI - Villosiclava virens infects specifically rice and barley stamen filaments due to the unique host cell walls. AB - Rice false smut, caused by the fungal pathogen Villosiclava virens, is one of the most important rice diseases in the world. Previous studies reported that the pathogen has less number of cell wall-degraded genes and attacks dominantly rice stamen filaments and extends intercellularly. To reveal why the fungus infects plant stamen filaments, inoculation test on barley was carried out with the similar protocol to rice. The experimental results showed that the fungus could penetrate quickly into barley stamen filaments and extends both intracellularly and intercellularly, usually resulting in severe damage of the stamen filament tissues. It also attacked young barley lodicules and grew intercellularly by chance. The light microscopic observations found that the epidermal and cortex cells in barley stamen filaments arranged loosely with very thick cell walls and large cell gaps. Cellulose microfibrils in barley stamen filament cell walls arranged very sparsely so that the cell walls looked like transparent. The cell walls were very soft and flexible, and often folded. However, V. virens extended dominantly in the noncellulose regions and seemed never to degrade microfibrils in barley and rice cell walls. This suggested that the unique structures of rice and barley stamen filaments should be fit for their function of elongation in anthesis, and also endow with the susceptibility to the fungus, V. virens. PMID- 27357264 TI - Heterozygous liver transplantation for maple syrup urine disease: First European reported case. AB - MSUD is an autosomal recessive metabolic disorder that results from a defect in the BCKDH enzyme. This enzyme is essential for the second step in the metabolism of the branched-chain amino acids, leucine, isoleucine, and valine. Patients with MSUD are subject to severe, irreversible neurologic injury unless closely managed with a specialized metabolic formula and a diet restricted in leucine throughout their lifetime. During times of illness, patients with MSUD can suffer from severe metabolic derangement, acute cerebral edema, and untimely death. Deceased donor liver transplant restores the ability to metabolize branched-chain amino acids, even on an unrestricted diet, and prevents metabolic derangements during times of illness. We report a successful case of living donor (parental) transplant for a child with MSUD. The donor was the child's father. This approach has been controversial as parents of children with MSUD are obligate heterozygotes for the condition and have diminished levels of BCKDH activity. If effective, living-related donor transplant provides a promising alternative for deceased donor liver transplant, which often requires a prolonged waiting period and may not be feasible in areas with limited medical resources. PMID- 27357265 TI - DLQI as a major criterion for introduction of systemic agents in patients with mild psoriasis. AB - BACKGROUND: Psoriasis is a skin inflammatory chronic disease with negative physical, psychological and social repercussions for those affected. However, patients suffering from mild disease also complain about negative impact on their quality of life, making it difficult for physicians to choose the best treatment strategy. OBJECTIVES: Understanding the impact of systemic treatments on Quality of Life (QoL) in patients with mild psoriasis in daily practice. METHODS: This is a monocentric retrospective study analysing patients affected by mild psoriasis [Psoriasis Area and Severity Index (PASI) <= 6]. Patients were divided into two groups, depending on the treatment decision taken by the physicians: patients who received local and/or UV light therapies and patients who were treated with systemic therapies as a first choice. PASI and Dermatology Life Quality Index (DLQI) scores were measured at each visit. RESULTS: Patients who received systemic therapies as a first choice reported higher QoL impairment, mainly due to psoriasis lesions localized on visible areas. During Follow-up, this group showed better improvement of PASI score and DLQI compared to patients receiving local and/or UV light treatment. CONCLUSIONS: Our findings highlight the potential benefit of using systemic therapies in patients with mild psoriasis and high QoL impairment. This study will help physicians to make the right therapeutic decision in patients suffering from mild psoriasis. PMID- 27357266 TI - sn-1,2-diacylglycerols protect against lethal endotoxemia by controlling systemic inflammation. AB - Systemic inflammation has emerged as a key pathophysiological process that induces multiple organ injuries and causes serious human diseases. Despite substantial evidence supporting the role of diacylglycerols (DAG) in modulating chronic inflammation and chronic diseases, the potential mechanisms of its involvement in TLRs-mediated inflammation are still unclear. Here, we show that sn-1,2-diacylglycerols modulate LPS/TLR4-mediated inflammation in vitro and in vivo. ELISA and western blotting experiments indicated that sn-1,2 diacylglycerols suppress LPS-induced responses, including IL-6 and TNF-alpha production, and COX-2 expression in mouse RAW264.7 macrophages and human endothelial cells, in a dose-dependent manner. Using LPS-induced murine model of systemic inflammation, we show that sn-1,2-diacylglycerols block the cytokine storm, the expression of inflammatory mediators, and LPS-induced septic lung damage and mortality. sn-1,2-diacylglycerols reduce systemic inflammation by inhibiting LPS-induced p38 MAPK- and PI3K/AKT-mediated NF-kappaB activation in macrophages. These results suggest that exogenous DAG probably acts by blocking p38 MAPK or PI3K/AKT signal transduction, thereby down-regulating NF-kappaB activation and NF-kappaB-mediated transcription of genes encoding cytokines and pro-inflammatory oxidative enzymes. Our findings demonstrate that exogenous sn 1,2-diacylglycerol protects mice from LPS-induced lethal endotoxemia by suppressing TLR4-driven inflammatory responses, suggesting that 1,2 diacylglycerols may be used as dietary health supplements for the prevention or therapy of systemic inflammatory diseases. PMID- 27357267 TI - Genome-wide differentiation in closely related populations: the roles of selection and geographic isolation. AB - Population divergence in geographic isolation is due to a combination of factors. Natural and sexual selection may be important in shaping patterns of population differentiation, a pattern referred to as 'isolation by adaptation' (IBA). IBA can be complementary to the well-known pattern of 'isolation by distance' (IBD), in which the divergence of closely related populations (via any evolutionary process) is associated with geographic isolation. The barn swallow Hirundo rustica complex comprises six closely related subspecies, where divergent sexual selection is associated with phenotypic differentiation among allopatric populations. To investigate the relative contributions of selection and geographic distance to genome-wide differentiation, we compared genotypic and phenotypic variation from 350 barn swallows sampled across eight populations (28 pairwise comparisons) from four different subspecies. We report a draft whole genome sequence for H. rustica, to which we aligned a set of 9493 single nucleotide polymorphisms (SNPs). Using statistical approaches to control for spatial autocorrelation of phenotypic variables and geographic distance, we find that divergence in traits related to migratory behaviour and sexual signalling, as well as geographic distance, together explain over 70% of genome-wide divergence among populations. Controlling for IBD, we find 42% of genomewide divergence is attributable to IBA through pairwise differences in traits related to migratory behaviour and sexual signalling alone. By (i) combining these results with prior studies of how selection shapes morphological differentiation and (ii) accounting for spatial autocorrelation, we infer that morphological adaptation plays a large role in shaping population-level differentiation in this group of closely related populations. PMID- 27357269 TI - Impact of activating transcription factor 4 signaling on lipogenesis in HepG2 cells. AB - Non-alcoholic fatty liver disease (NAFLD) is a rapidly growing health threat that has previously been associated with lipogenesis. The direct effect of endoplasmic reticulum stress (ERS) inhibition on the induction of lipogenesis has not been investigated in hepatocytes in vitro. The impact of activating transcription factor-4 (ATF4) on the lipogenic pathway and hepatic insulin transduction in liver cells also requires further investigation. In the present study, the triglyceride (TG) content of HepG2 cells stimulated with fructose was investigated using a commercially available enzymatic assay, and the expression levels of lipogenesis-associated factors were determined by western blotting and reverse transcription-quantitative polymerase chain reaction. Notably, the TG content of HepG2 cells was increased following incubation with fructose, which was accompanied by ERS. 4-Phenylbutyric acid, an inhibitor of ERS, lowered the TG content by reducing the mRNA expression levels of sterol regulatory element binding protein 1 (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP), and the protein expression levels of fatty acid synthase (FAS), acetyl CoA carboxylase (ACC) and stearoyl-CoA desaturase-1 (SCD-1). Conversely, tunicamycin, which is an inducer of ERS, increased the TG content and stimulated the expression of the above lipogeneic markers. ATF4 deficiency relieved TG accumulation and decreased the mRNA expression levels of SREBP-1c and ChREBP, and protein expression levels of FAS, ACC and SCD-1 in fructose-treated HepG2 cells. Conversely, ATF4 overexpression increased the TG content by upregulating the mRNA expression levels of SREBP-1c and ChREBP and protein expression levels of FAS, ACC and SCD-1. Inhibition of ERS was shown to protect HepG2 cells against fructose-induced TG accumulation, whereas induction of ERS stimulated hepatic lipogenesis. As a downstream transcription factor of the unfolded protein response, a deficiency in ATF4 attenuates fructose-induced lipogenesis; while an overexpression of ATF4 can induce TG accumulation through stimulating hepatic lipogenesis. The results of the present study suggested that ATF4 may exert various physiological roles in lipid metabolism depending on the nutrient composition. In addition, these results suggested that ATF4 has a role in regulating lipogenesis and in the development of NAFLD; thus ATF4 may be considered a therapeutic target for NAFLD. PMID- 27357268 TI - HuR in pheochromocytomas and paragangliomas - overexpression in verified malignant tumors. AB - Pheochromocytomas and paragangliomas are rare, neural crest-originating, neuroendocrine tumors. HuR is an mRNA-binding protein of the ELAV/Hu-protein family, which participates in posttranscriptional regulation of many cancer associated genes. HuR expression has been connected with aggressive behavior of several malignancies. Cyclooxygenase-2 (COX-2) is also expressed in several malignant tumors, and its expression is regulated by HuR. Tissue microarray of 153 primary pheochromocytomas and paragangliomas was investigated for the expression of HuR and COX-2 proteins by immunohistochemistry using two different HuR antibodies (HuR19F12 and HuR3A). In these tumors, the expression of both intranuclear and cytoplasmic HuR was detectable. Increased cytoplasmic HuR expression was significantly associated with metastatic tumors. Increased COX-2 and MIB-1 expression also was associated with metastatic potential, and moreover, HuR and COX-2 expression correlated with each other. Our data suggest that increased expression of HuR protein is associated with metastatic potential of paragangliomas and pheochromocytomas, and COX-2 seems to be a target of HuR. PMID- 27357270 TI - Cytokine and Growth Factor Concentrations in Canine Autologous Conditioned Serum. AB - OBJECTIVE: To compare cytokine and growth factor concentrations in canine autologous conditioned serum (ACS) to canine plasma. STUDY DESIGN: Experimental in vivo study. ANIMALS: Client-owned, adult dogs (n=22). METHODS: Blood collected from 16 medium to large breed dogs was used to produce ACS (Orthokine((r)) vet irap 10 syringes) and citrated plasma (control). Canine-specific ELISA assays were run per manufacturers' instructions for interleukin (IL)-10, IL-4, tumor necrosis factor (TNF)-alpha, insulin-like growth factor (IGF)-1, fibroblast growth factor (FGF)-2, transforming growth factor (TGF)-beta1, IL-1beta, and interleukin-1 receptor antagonist (IL-1ra). Serum, in addition to plasma and ACS, was collected from an additional 6 dogs for TNF-alpha, IL-1beta, and IL-1ra analysis (total of 22 dogs). Data were analyzed for differences in each cytokine concentration using pairwise comparisons between ACS, plasma, and serum using Wilcoxon signed-rank tests. Significance was set at P<.05. RESULTS: There was a large variability in growth factor and cytokine concentrations in ACS and plasma for individual dogs. There were no significant differences in IL-10, TNF-alpha, IGF-1, FGF-2, and TGF-beta1 concentrations between ACS, plasma, and serum. The IL 1beta concentrations in ACS (median, range 46.3 pg/mL, 0-828.8) and IL-4 (0.0 pg/mL, 0-244.1) were significantly higher than plasma (36.6 pg/mL, 0-657.1 and 0.0 pg/mL, 0-0, respectively). The IL-1ra concentration in ACS (median, range 3,458.9 pg/mL, 1,243.1-12,089.0) was significantly higher than plasma (692.3 pg/mL, 422.5-1,475.6). The IL-1ra:IL-1beta ratio in ACS was significantly higher than plasma (39.9 vs. 7.2). CONCLUSION: IL-1ra concentrations in canine ACS were comparable to those published for people and horses and pro-inflammatory cytokines remained low in canine ACS. PMID- 27357271 TI - Mineralization of the Equine Palmar/Plantar Annular Ligament Treated by Surgical Resection. AB - OBJECTIVE: To document the clinical presentation, diagnosis, and surgical treatment of mineralization of the equine palmar/plantar annular ligament (PAL). STUDY DESIGN: Retrospective study. ANIMALS: Ponies (n=7). METHODS: Case records from 2 referral hospitals were examined to identify cases with lameness associated with PAL mineralization treated surgically. Follow-up information was obtained from the owners by telephone questionnaire. RESULTS: Duration of lameness before referral ranged from 5 weeks to 6 months, and degree of lameness from grade 1 to 5 out of 10. In 3 cases, records noted obvious pain when pressure was applied over the PAL. Pain resulting in lameness was localized to this area and all cases were treated surgically, although the extent of resected tissue varied among cases. Histological examination of resected tissue (4 cases) revealed fibrocartilaginous and/or osseous metaplasia. Following surgery, 6 of the 7 ponies became sound. CONCLUSION: Based on this limited case series, surgical treatment for mineralization of the PAL offers a favorable success rate without severe complications where conservative methods have failed. PMID- 27357272 TI - Prospective Evaluation of the Leipzig Stifle Distractor. AB - OBJECTIVES: To evaluate the Leipzig Stifle Distractor (LSD) for arthroscopic evaluation of the medial meniscus. STUDY DESIGN: Prospective clinical multi center study. ANIMALS: 64 stifles of 64 dogs (mean body weight 35 kg) with suspected cranial cruciate ligament rupture. METHODS: The LSD was used to distract the medial compartment and to evaluate the medial meniscus. The degree of exposure of the caudal pole of the medial meniscus (CMM) and ease of diagnosis was quantified after either distraction with the LSD or manipulation of the stifle with valgus stress and external rotation. Time for pin placement, level of difficulty and associated complications with LSD application were recorded. Medial collateral ligament integrity was tested by stress radiographs. RESULTS: The mean time for applying the LSD was 1.4 minutes (range 0.5-3.0). Application was considered easy in 90% and moderate in 10% of joints, with no complications recorded. LSD application increased exposure (P < .001) and facilitated probing of the CMM (P < .001), allowing for the diagnosis of 10 meniscal tears missed without the LSD. The use of LSD increased the likelihood of diagnosing a meniscal tear by 1.9 times. Based on the stress radiographs, medial collateral ligament integrity was maintained in all tested stifles. CONCLUSION: Diagnosis of medial meniscal tears was improved using LSD. The LSD provided a safe and effective method for improved visualization and access to the caudal portion of the medial meniscus, which may allow for better arthroscopic assessment of meniscal pathology in dogs. PMID- 27357273 TI - Feasibility of Stifle Medial Meniscal Release in Toy Breed Dogs with and without a Joint Distractor. AB - OBJECTIVE: To investigate the feasibility of medial meniscal release (MMR) during stifle arthroscopy in toy breed dogs with and without a joint distractor. STUDY DESIGN: Experimental cadaveric study. SAMPLE POPULATION: Stifles (n = 40) from 20 canine cadavers (1.8-5.1 kg). METHODS: Paired stifles were randomly assigned to the joint distractor group and the control group (n = 20 each). All stifles underwent arthroscopic transection of the cranial cruciate ligament followed by a release of the caudomedial meniscotibial ligament. After the procedures, all stifles were disarticulated. The degree of released meniscus was recorded subjectively by 5% increments. A MMR success was defined as a complete transection. The areas of femoral and tibial articular cartilage damage were calculated using india ink staining and digital imaging. The results were compared between groups and odds ratios were calculated. RESULTS: All stifle arthroscopies were successful. The success rate of MMR was significantly higher (P = .013) with a joint distractor than without a joint distractor. MMR was 7.4 times more likely to succeed with a joint distractor than without a joint distractor. The distal femoral articular cartilage was significantly more damaged (P = .011) in the stifles without a joint distractor than in the stifles with a distractor. No difference was found between the 2 groups for damage to the tibial cartilage (P = .058). CONCLUSION: Stifle arthroscopic MMR is feasible in toy breed dogs. Using a joint distractor is recommended for arthroscopic treatment based on our results because it significantly reduced the rate of incomplete release as well as iatrogenic cartilage damage. PMID- 27357274 TI - Canine Elbow Realignment Osteotomy (CERO): Validation of the Accuracy of Acute Radial Lengthening in a Cadaveric Incongruency Model. AB - OBJECTIVE: To verify the ability of a novel Canine Elbow Realignment Osteotomy (CERO) system for acute axial radial or ulnar lengthening to restore normal elbow congruency in a shortened radius cadaver model using assessment by computed tomography (CT). STUDY DESIGN: In vitro cadaver study. ANIMALS: Five pairs of greyhound forelimbs from animals euthanatized for reasons unrelated to the study. METHODS: CT of each elbow was performed (1) pre-operatively (pre-op), (2) after placement of a linear motor IMEXTM external skeletal fixator (ESF) on the radius with diaphyseal ostectomy and radial shorting of 1-5 mm (post-ESF), and (3) after CERO surgery to lengthen the radius proximal to the ostectomy site by an amount equal to the degree of radial shortening (post-CERO). The joint space at 7 loci on dorsal plane and 6 loci on sagittal plane reconstructions was measured to assess changes in joint congruity between pre-op, post-ESF, and post-CERO. Repeated measures ANOVA with post hoc comparisons were performed to compare measurements between the 3 groups. RESULTS: Mean joint space measurements at most loci in the dorsal and sagittal planes were significantly different post-ESF compared with pre-op, confirming development of joint incongruency with the model. Post-CERO joint space measurements did not differ significantly compared with pre-op measurements, demonstrating the return to normal joint congruency using the CERO procedure. CONCLUSION: CERO surgery restored humeroradioulnar congruency in our cadaver model and may have application for acute correction of axial radial or ulnar incongruency in canine elbows secondary to elbow dysplasia or premature growth plate closure. PMID- 27357275 TI - Prospective Randomized Clinical and Radiographic Evaluation of a Novel Bioabsorbable Biocomposite Tibial Tuberosity Advancement Cage Implant. AB - OBJECTIVE: To evaluate the suitability of a novel bioabsorbable biocomposite cage (BC) implant for use in tibial tuberosity advancement (TTA) surgery in dogs with cranial cruciate ligament (CrCL) disease and to compare radiographic osteotomy healing scores and complications between groups that received either a BC or stainless steel cage (SSC). STUDY DESIGN: Prospective randomized clinical study. ANIMALS: Dogs with unilateral CrCL rupture (n=56). METHODS: TTA was performed in 60 consecutive dogs using either a BC (30 dogs) or SSC (30 dogs). Patient parameters, 6 week and 6 month postoperative radiographic osteotomy healing scores, time elapsed to postoperative rechecks, and complications were compared between groups. Osteotomy healing was graded using a 5-point (0-4) scale. Data were analyzed using Wilcoxon Rank Sum tests and chi(2) tests with significance set at P<.05. RESULTS: Fifty-six dogs (30 BC, 26 SSC) had complete medical and radiographic records at 6 months for inclusion in data analysis. Three complications occurred in the BC group (1 major, 2 minor) and 2 occurred in the SSC group (2 minor). There was no statistical difference in patient parameters, 6 week healing scores, or complications between BC and SSC groups. Healing scores at 6 months were significantly higher in the BC group (3.3 +/- 0.52) compared to the SSC group (2.9 +/- 0.69; P=.04). CONCLUSION: Based on improved BC osteotomy healing scores 6 months after surgery with no significant differences in complications compared to SSC, BC TTA cages are a viable alternative to SSC. PMID- 27357276 TI - Complication Rates After Bilateral versus Unilateral Total Ear Canal Ablation with Lateral Bulla Osteotomy for End-Stage Inflammatory Ear Disease in Dogs: 79 Ears. AB - OBJECTIVE: To determine whether perioperative complication rates are different between unilateral (ULS) versus single-stage bilateral (BLSS) total ear canal ablation-lateral bulla osteotomy (TECA-LBO) surgeries. STUDY DESIGN: Retrospective case series. ANIMALS: Fifity-seven dogs (79 ears) undergoing TECA LBO at a single institution over 14 years. METHODS: Medical records of dogs undergoing TECA-LBO for end-stage inflammatory non-neoplastic ear disease from March 1999 to September 2013 at the Colorado State University Veterinary Teaching Hospital were evaluated for intraoperative and early postoperative complications associated with the procedure. Inclusion criteria were clinical and/or histopathologic diagnosis of chronic otitis externa, surgical treatment by TECA LBO, and a minimum of 2 week follow-up data. RESULTS: Twenty dogs (40 ears) underwent BLSS and 37 dogs (39 ears) had ULS. Complications were recorded for 29 of 40 ears (72.5%) in the BLSS group (40.0% facial nerve, 15.0% ocular, and 32.5% minor incisional complications) and 25 of 39 ears (64.1%) in the ULS group (33.3% facial nerve, 12.8% ocular, and 23.1% minor incisional complications). Dogs undergoing BLSS did not have a significantly higher total complication rate, or higher neurologic, ocular, or incisional complication rates, than the ULS procedure. No major anesthetic complications affecting outcome were recorded for either group. CONCLUSION: Anesthetic and early surgical complication rates after ULS and BLSS were not significantly different in our study. Offering single-stage bilateral TECA-LBO procedures for otherwise healthy dogs with end-stage inflammatory otitis externa is a viable treatment option without additional risk for complication. PMID- 27357277 TI - Update on Current Evidence for Hepatitis C Therapeutic Options in HCV Mono infected Patients. AB - PURPOSE OF REVIEW: Therapies for hepatitis C (HCV) are evolving rapidly with the advent of novel direct-acting antiviral agents (DAAs). We review evidence for currently or imminently available regimens to aide clinicians in understanding current therapeutic options. RECENT FINDINGS: A number of DAA combinations have completed clinical trials and are available for use. Current combinations are often genotype-specific, and combine HCV protease inhibitors, NS5A inhibitors and/or NS5B inhibitors to suppress HCV replication, leading to eradication. Current potential combinations for genotype 1 infection include sofosbuvir ledipasvir, paritaprevir/ritonavir-ombitasvir-dasabuvir, sofosbuvir with daclatasvir, and grazoprevir-elbasvir. These regimens have been associated with sustained virologic response (SVR) rates of over 95 % for treatment naive individuals after 12 weeks of therapy regardless of cirrhosis, and some sub groups of patients may be successfully treated with just 8 weeks of sofosbuvir ledipasvir. Regimens for genotype 2 and 3 include sofosbuvir with ribavirin, sofosbuvir with daclatasvir, or with velpatasvir, which may offer highest SVR rates when available. The development of HCV drug resistance, particularly against NS5A agents, may impact subsequent regimens. The need for baseline screening for resistant variants is unclear for most regimens, but likely would affect only a minority of patients. All-oral curative regimens for HCV are now possible for most patients. PMID- 27357279 TI - Isolation of an imported subgenotype B5 strain of human enterovirus A71 in Chongqing City, China, 2014. AB - BACKGROUND: Enterovirus A71 (EV-A71) is the main pathogen responsible for large outbreaks of hand, foot, and mouth disease (HFMD) in mainland China, and the dominant EV-A71 strains belong to subgenotype C4. To date, only one imported subgenotype B5 of EV-A71 has been reported in Xiamen City Fujian Province, 2009. RESULTS: Here, we report on another imported subgenotype B5 of EV-A71 isolated from a HFMD patient in Chongqing City in 2014 (strain CQ2014-86/CQ/CHN/2014, hereafter refer as CQ2014-86). The VP1 coding sequence and the whole genome sequence revealed that strain CQ2014-86 shares the high nucleotide identity with Vietnamese strains isolated in 2011-2013, suggesting that strain CQ2014-86 may have been imported from Vietnam. In the 5'UTR, P2 and P3 regions, recombination events were found between strain CQ2014-86 and other EV-A, such as coxsackievirus A4 (CV-A4), CV-A5, CV-A14 and CV-A16. CONCLUSIONS: This is the second report on importation of subgenotype B5 of EV-A71 in China, implying that we need to pay more attention to the importation of different subgenotypes of EV-A71. PMID- 27357280 TI - A case of drug-induced lupus erythematosus secondary to trimethoprim/sulfamethoxazole presenting with pleural effusions and pericardial tamponade. AB - We report a case of drug-induced lupus erythematosus (DILE) secondary to trimethoprim/sulfamethoxazole (TMP/SMX) in a patient with underlying inflammatory bowel disease (IBD). The initial presentation was with febrile pleural and pericardial effusions followed by cardiac tamponade. The patient was treated with a short course of corticosteroids with complete resolution of symptoms. To our knowledge this is the first reported case of TMP/SMX-induced DILE presenting with life-threatening serositis. When confronted with sterile exudative effusions, clinicians should strongly consider non-infectious etiologies. PMID- 27357283 TI - Surgical management of carotid body tumor - Is Shamblin classification sufficient to predict surgical outcome? AB - Background The study aims to conduct a review of the surgical management of carotid body tumor. Methods Consecutive patients with CBT who received surgical interventions from January 1994 to January 2014 at our institution were reviewed. Clinical, operative, pathological and follow up information were reported. Results Twenty patients (four males; median age was 36) with 21 CBT operations were recorded during the period. One patient undertook sequential operations for bilateral CBTs. Patients had 19 neck mass, 1 incidental finding and 1 facial nerve palsy. Six CBTs (28.6%) were Shamblin class I, ten (47.6%) were class II and five (23.8%) were class III. Nine CBTs had preoperative conjunctive embolization. Two operations required internal carotid artery resection and reconstruction. Four patients received subtotal resections, while 17 achieved complete resection. Complications included two major strokes, three hoarse voice and two Horner's syndrome. Shamblin class was significant predictor of operative time, blood loss, and whether complete resection accomplished, but could not predict postoperative complication. With median follow up period of 94 months, there was no tumor recurrence found in those had complete resection. Conclusions This small cohort showed that Shamblin class was significant in predicting technical difficulties but could not predict occurrence of complications. PMID- 27357281 TI - Cerebrospinal fluid levels of neopterin are elevated in delirium after hip fracture. AB - BACKGROUND: The inflammatory cell product neopterin is elevated in serum before and during delirium. This suggests a role for disordered cell-mediated immunity or oxidative stress. Cerebrospinal fluid (CSF) neopterin levels reflect brain neopterin levels more closely than serum levels. Here we hypothesized that CSF neopterin levels would be higher in delirium. METHODS: In this prospective cohort study, 139 elderly patients with acute hip fracture were recruited in Oslo and Edinburgh. Delirium was diagnosed with the confusion assessment method performed daily pre-operatively and on the first 5 days post-operatively. Paired CSF and blood samples were collected at the onset of spinal anaesthesia. Neopterin levels were measured using high-performance liquid chromatography. RESULTS: Sixty-four (46 %) of 139 hip fracture patients developed delirium perioperatively. CSF neopterin levels were higher in delirium compared to controls (median 29.6 vs 24.7 nmol/mL, p = 0.003), with highest levels in patients who developed delirium post-operatively. Serum neopterin levels were also higher in delirium (median 37.0 vs 27.1 nmol/mL, p = 0.003). CSF neopterin remained significantly associated with delirium after controlling for relevant risk factors. Higher neopterin levels were associated with poorer outcomes (death or new institutionalization) 1 year after surgery (p = 0.02 for CSF and p = 0.03 for serum). CONCLUSIONS: This study is the first to examine neopterin in CSF from patients with delirium. Our findings suggest potential roles for activation of cell-mediated immune responses or oxidative stress in the delirium process. High levels of serum or CSF neopterin in hip fracture patients may also be useful in predicting poor outcomes. PMID- 27357282 TI - Variants in ACPP are associated with cerebrospinal fluid Prostatic Acid Phosphatase levels. AB - BACKGROUND: Prostatic Acid Phosphatase (PAP) is an enzyme that is produced primarily in the prostate and functions as a cell growth regulator and potential tumor suppressor. Understanding the genetic regulation of this enzyme is important because PAP plays an important role in prostate cancer and is expressed in other tissues such as the brain. METHODS: We tested association between 5.8 M SNPs and PAP levels in cerebrospinal fluid across 543 individuals in two datasets using linear regression. We then performed meta-analyses using METAL =with a significance threshold of p < 5 * 10(-8) and removed SNPs where the direction of the effect was different between the two datasets, identifying 289 candidate SNPs that affect PAP cerebrospinal fluid levels. We analyzed each of these SNPs individually and prioritized SNPs that had biologically meaningful functional annotations in wANNOVAR (e.g. non-synonymous, stop gain, 3' UTR, etc.) or had a RegulomeDB score less than 3. RESULTS: Thirteen SNPs met our criteria, suggesting they are candidate causal alleles that underlie ACPP regulation and expression. CONCLUSIONS: Given PAP's expression in the brain and its role as a cell-growth regulator and tumor suppressor, our results have important implications in brain health such as cancer and other brain diseases including neurodegenerative diseases (e.g., Alzheimer's disease and Parkinson's disease) and mental health (e.g., anxiety, depression, and schizophrenia). PMID- 27357285 TI - Controversies surrounding continuous deep sedation at the end of life: the parliamentary and societal debates in France. AB - BACKGROUND: Continuous deep sedation at the end of life is a practice that has been the topic of considerable ethical debate, for example surrounding its perceived similarity or dissimilarity with physician-assisted dying. The practice is generally considered to be legal as a form of symptom control, although this is mostly only assumed. France has passed an amendment to the Public Health Act that would grant certain terminally ill patients an explicit right to continuous deep sedation until they pass away. Such a framework would be unique in the world. DISCUSSION: In this paper we will highlight and reflect on four relevant aspects and shortcomings of the proposed bill. First, that the bill suggests that continuous deeps sedation should be considered as a sui generis practice. Second, that it requires that sedation should always be accompanied by the withholding of all artificial nutrition and hydration. In the most recently amended version of the legal proposal it is stated that life sustaining treatments are withheld unless the patient objects. Third, that the French bill would not require that the suffering for which continuous deep sedation is initiated is unbearable. Fourth, the question as to whether the proposal should be considered as a way to avoid having to decriminalise euthanasia and/or PAS or, on the contrary, as a veiled way to decriminalise these practices. The French proposal to amend the Public Health Act to include a right to continuous deep sedation for some patients is a unique opportunity to clarify the legality of continuous deep sedation as an end-of-life practice. Moreover, it would recognize that the practice of continuous deep sedation raises ethical and legal issues that are different from those raised by symptom control on the one hand and assisted dying on the other hand. Nevertheless, there are still various issues of significant ethical concern in the French legislative proposal. PMID- 27357284 TI - Developmental programming: rescuing disruptions in preovulatory follicle growth and steroidogenesis from prenatal testosterone disruption. AB - BACKGROUND: Prenatal testosterone (T) excess from days 30-90 of gestation disrupts gonadotropin surge and ovarian follicular dynamics and induces insulin resistance and functional hyperandrogenism in sheep. T treatment from days 60-90 of gestation produces a milder phenotype, albeit with reduced fecundity. Using this milder phenotype, the aim of this study was to understand the relative postnatal contributions of androgen and insulin in mediating the prenatal T induced disruptions in ovarian follicular dynamics. METHODS: Four experimental groups were generated: 1) control (vehicle treatment), 2) prenatal T-treated (100 mg i.m. administration of T propionate twice weekly from days 60-90 of gestation), 3) prenatal T plus postnatal anti-androgen treated (daily oral dose of 15 mg/kg/day of flutamide beginning at 8 weeks of age) and 4) prenatal T and postnatal insulin sensitizer-treated (daily oral dose of 8 mg/day rosiglitazone beginning at 8 weeks of age). Follicular response to a controlled ovarian stimulation protocol was tested during their third breeding season. Main outcome measures included the determination of number and size of ovarian follicles and intrafollicular concentrations of steroids. RESULTS: At the end of the controlled ovarian stimulation, the number of follicles approaching ovulatory size (>=6 mm) were ~35 % lower in prenatal T-treated (6.5 +/- 1.8) compared to controls (9.8 +/ 2.0). Postnatal anti-androgen (10.3 +/- 1.9), but not insulin sensitizer (5.0 +/ 0.9), treatment prevented this decrease. Preovulatory sized follicles in the T group had lower intrafollicular T, androstenedione, and progesterone compared to that of the control group. Intrafollicular steroid disruption was partially reversed solely by postnatal insulin sensitizer treatment. CONCLUSIONS: These results demonstrate that the final preovulatory follicular growth and intrafollicular steroid milieu is impaired in prenatal T-treated females. The findings are consistent with the lower fertility rate reported earlier in these females. The finding that final follicle growth was fully rescued by postnatal anti-androgen treatment and intrafollicular steroid milieu partially by insulin sensitizer treatment suggest that both androgenic and insulin pathway disruptions contribute to the compromised follicular phenotype of prenatal T-treated females. PMID- 27357288 TI - Discordant Mismatch Repair Protein Immunoreactivity in Lynch Syndrome-Associated Neoplasms: A Recommendation for Screening Synchronous/Metachronous Neoplasms. AB - OBJECTIVES: Lynch syndrome (LS) predisposes individuals to developing synchronous and metachronous LS-associated neoplasms (LSANs). Mismatch repair protein (MMRP) immunohistochemistry (IHC) is widely used to identify LS, but its utility in patients with synchronous/metachronous lesions has not been studied. We studied MMRP IHC in patients with LS with more than one LSAN to provide screening recommendations in patients with synchronous/metachronous neoplasms. METHODS: All patients with LS diagnosed at The Ohio State University Wexner Medical Center from 2009 through 2014 with more than one LSAN and available tumor tissue for immunostaining were identified. Tumors were stained for MLH1, MSH2, MSH6, and PMS 2 proteins, and immunoreactivity was scored as intact or lost. RESULTS: Thirteen patients with LS with 29 synchronous and/or metachronous primary LSANs were identified. Neoplasms involved large and small intestine (n = 19), ampulla (n = 1), endometrium (n = 1), and skin (sebaceous neoplasms, n = 8). Nine (69%) of 13 patients showed concordant MMRP results in all tumors, and four (31%) showed discordant MMRP results. CONCLUSIONS: LS diagnosis could have been missed in 31% of the study cases if only the LSAN exhibiting intact MMRP expression was screened. Accordingly, our findings support the recommendation to perform LS screening in all primary, synchronous, and metachronous intestinal and endometrial cancers if a previous tumor screened intact. PMID- 27357286 TI - The relationship between complement factor C3, APOE epsilon4, amyloid and tau in Alzheimer's disease. AB - Inflammation is becoming increasingly recognized as an important contributor to Alzheimer's disease (AD) pathogenesis. As a part of the innate immune system, the complement cascade enhances the body's ability to destroy and remove pathogens and has recently been shown to influence Alzheimer's associated amyloid and tau pathology. However, little is known in humans about the effects of the complement system and genetic modifiers of AD risk like the epsilon4 allele of apolioprotein E (APOE epsilon4) on AD pathobiology. We evaluated cerebrospinal fluid (CSF) protein levels from 267 individuals clinically diagnosed as cognitively normal, mild cognitive impairment, and AD. Using linear models, we assessed the relationship between APOE epsilon4 genotype, CSF Complement 3 (C3), CSF amyloid beta (amyloid) and CSF hyperphosphorylated tau (ptau). We found a significant interaction between APOE epsilon4 and CSF C3 on both CSF amyloid and CSF ptau. We also found that CSF C3 is only associated with CSF ptau after accounting for CSF amyloid. Our results support a conceptual model of the AD pathogenic cascade where a synergistic relationship between the complement cascade (C3) and APOE epsilon4 results in elevated Alzheimer's neurodegeneration and in turn, amyloid further regulates the effect of the complement cascade on downstream tau pathology. PMID- 27357287 TI - Multiple regulatory variants located in cell type-specific enhancers within the PKP2 locus form major risk and protective haplotypes for canine atopic dermatitis in German shepherd dogs. AB - BACKGROUND: Canine atopic dermatitis (CAD) is a chronic inflammatory skin disease triggered by allergic reactions involving IgE antibodies directed towards environmental allergens. We previously identified a ~1.5 Mb locus on canine chromosome 27 associated with CAD in German shepherd dogs (GSDs). Fine-mapping indicated association closest to the PKP2 gene encoding plakophilin 2. RESULTS: Additional genotyping and association analyses in GSDs combined with control dogs from five breeds with low-risk for CAD revealed the top SNP 27:19,086,778 (p = 1.4 * 10(-7)) and a rare ~48 kb risk haplotype overlapping the PKP2 gene and shared only with other high-risk CAD breeds. We selected altogether nine SNPs (four top-associated in GSDs and five within the ~48 kb risk haplotype) that spanned ~280 kb forming one risk haplotype carried by 35 % of the GSD cases and 10 % of the GSD controls (OR = 5.1, p = 5.9 * 10(-5)), and another haplotype present in 85 % of the GSD cases and 98 % of the GSD controls and conferring a protective effect against CAD in GSDs (OR = 0.14, p = 0.0032). Eight of these SNPs were analyzed for transcriptional regulation using reporter assays where all tested regions exerted regulatory effects on transcription in epithelial and/or immune cell lines, and seven SNPs showed allelic differences. The DNA fragment with the top-associated SNP 27:19,086,778 displayed the highest activity in keratinocytes with 11-fold induction of transcription by the risk allele versus 8 fold by the control allele (pdifference = 0.003), and also mapped close (~3 kb) to an ENCODE skin-specific enhancer region. CONCLUSIONS: Our experiments indicate that multiple CAD-associated genetic variants located in cell type-specific enhancers are involved in gene regulation in different cells and tissues. No single causative variant alone, but rather multiple variants combined in a risk haplotype likely contribute to an altered expression of the PKP2 gene, and possibly nearby genes, in immune and epithelial cells, and predispose GSDs to CAD. PMID- 27357289 TI - Does Taking the Fellowship In-Service Hematopathology Examination and Performance Relate to Success on the American Board of Pathology Hematology Examination? AB - OBJECTIVES: The biannual Fellow In-Service Hematopathology Examination (FISHE) assesses knowledge in five content areas. We examined the relationship between taking the FISHE and performance on it with outcomes on the first attempted American Board of Pathology Hematology subspecialty certifying examination (ABP HE). METHODS: The pass rate between the ABP-HE candidates who took the spring FISHE and those who did not were compared. The likelihood of fellows passing the ABP-HE based on their percentiles on the FISHE was also assessed. RESULTS: ABP-HE candidates who took the spring FISHE had a higher pass rate (96.4%) than those who did not (76.1%, P < .001). Spring FISHE performance, including total percentile and percentiles in four of five FISHE content areas, was only a weak predictor of passing the ABP-HE. CONCLUSIONS: Candidates who take the spring FISHE do better on the ABP-HE than those who do not. Most fellows passed the first attempted ABP-HE regardless of FISHE performance. Whether this is due to fellows making use of the FISHE as a self-evaluation tool to help identify and then correct their knowledge deficiencies remains to be determined. PMID- 27357290 TI - Neonatal Intensive Care Unit Quality Initiative: Identifying Preanalytical Variables Contributing to Specimen Hemolysis and Measuring the Impact of Evidence Based Practice Interventions. AB - OBJECTIVES: Blood specimen hemolysis is a major cause of sample recollection in the neonatal intensive care unit. We aimed to reduce the hemolysis rate from 6.3% at baseline to less than 4% within the 9 months' duration of the study. METHODS: Intravenous infusion of lipid emulsion during sample collection, sample collection site, and blood sample transportation methods were investigated as possible contributors to hemolysis. Subsequently, two practice improvements were implemented: pausing lipid emulsion infusion prior to collection and slowing withdrawal rates through arterial catheters. RESULTS: Samples were more likely to be hemolyzed if they were collected during lipid infusion and subsequently transported by pneumatic tube or collected through an arterial catheter. Retrospective analysis demonstrated a decreased number of tests cancelled due to specimen hemolysis (3.5%) after our interventions. CONCLUSIONS: We identified three variables contributing to hemolysis and instituted two clinical practice interventions to significantly reduce test cancellations due to hemolysis. PMID- 27357291 TI - Evaluation of a Methotrexate Chemiluminescent Microparticle Immunoassay: Comparison to Fluorescence Polarization Immunoassay and Liquid Chromatography Tandem Mass Spectrometry. AB - OBJECTIVES: For most laboratories, methotrexate (MTX) concentrations are routinely monitored by fluorescence polarization immunoassay (FPIA). In anticipation of an announced withdrawal of the FPIA reagent on the Abbott TDxFLx (Abbott Diagnostics, Abbott Park, IL), we have evaluated a new reagent kit developed by Abbott on the Architect i1000, based on chemiluminescent microparticle immunoassay (CMIA). METHODS: Precision, inaccuracy, and selectivity were assessed. Interassay variability was established using 75 plasma patient samples treated with MTX and analyzed by two methods: FPIA and liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS FOR MTX,: the intraday inaccuracy was between -6.37% and +3.52%, while interday performance was between -3.70% and 7.90%. Intraday and interday imprecision was less than 2.65% and less than 2.22%, respectively. The correlation coefficient between CMIA and FPIA or LC-MS/MS was 0.9969 and 0.9985, respectively. CONCLUSIONS: These results comparing CMIA vs FPIA and LC-MS/MS indicate that CMIA is a suitable alternative to the FPIA method. PMID- 27357292 TI - Transportation Cooler Interventions Reduce Plasma and RBC Product Wastage. AB - OBJECTIVES: The rate of plasma product wastage for the United States in 2011 was approximately 1.8%. The plasma wastage rate at our institution was higher, mainly due to products returned out of temperature range from procedural areas. A process review and intervention to reduce plasma wastage was undertaken, which included modifications to our transport cooler. METHODS: A new cooler system was designed, and this device was implemented alongside an updated protocol for delivering plasma while also enhancing the previous RBC cooler validation time. We audited plasma and RBC product wastage prior to these interventions, from January 2013 to February 2014, vs after the intervention from April 2014 to March 2015. RESULTS: After the intervention, the monthly plasma wastage rate declined 60% (12.6 units/100 units transfused preintervention vs 5.0 units/100 units transfused postintervention; P < .0001). The monthly RBC wastage rate also decreased 28% (3.2 units/100 units transfused preintervention vs 2.3 units/100 units transfused postintervention; P < .01). CONCLUSIONS: Our intervention resulted in significantly decreased plasma and RBC wastage and is broadly applicable, since out-of-temperature product wastage in procedural areas is likely a significant problem at many institutions. PMID- 27357293 TI - Evaluation of the Sebia Capillarys 3 Tera and the Bio-Rad D-100 Systems for the Measurement of Hemoglobin A1c. AB - OBJECTIVES: We evaluated the Bio-Rad (Irvine, CA) D-100 and the Sebia (Lisses, France) Capillarys 3 Tera for the measurement of hemoglobin A1c (HbA1c) in venous blood samples. METHODS: Whole-blood samples and control material were analyzed with the D-100 and Capillarys 3 Tera and compared with our routine method, HLC 723G7 (Tosoh, Tokyo, Japan). An evaluation protocol to test precision, trueness, linearity, carryover, and selectivity was set up according to Clinical and Laboratory Standards Institute guidelines. The results were presented in National Glycohemoglobin Standardization Program and International Federation of Clinical Chemistry (IFCC) units. RESULTS: Both systems showed excellent precision (total coefficients of variation <2%, IFCC) and bias (<0.3% or 3 mmol/mol). Linearity was demonstrated for HbA1c values from 3.8% (18 mmol/mol) to 18.5% (179 mmol/mol). Results were correlated with the routine method using Bland-Altman analysis, showing a mean difference of 0.33% or 3.6 mmol/mol for the D-100 and of 0.25% or 2.6 mmol/mol for the Capillarys 3 Tera vs HLC-723G7. None of the automated instruments were prone to interferences by labile HbA1c (<=10 g/L glucose), carbamylated hemoglobin (<=0.5 mmol/L potassium cyanate), hemoglobin variants, bilirubin (<=15 mg/dL), and triglycerides (<=3,360 mg/dL). CONCLUSIONS: The Bio-Rad D-100 and the Sebia Capillarys 3 Tera instruments performed well for the determination of HbA1c in terms of quality criteria as well as for sample throughput. PMID- 27357294 TI - Pathologic Studies of Fatal Encephalomyelitis in Children Caused by Enterovirus 71. AB - OBJECTIVES: Enterovirus 71 (EV71) is the major pathogen of hand, foot, and mouth disease and can cause death; however, its pathogenesis remains elusive. METHODS: We performed a detailed systematic histopathologic examination and molecular studies on six autopsy cases of EV71 infection using H&E, immunohistochemistry, double immunofluorescence staining, and nested reverse transcription polymerase chain reaction. RESULTS: Characteristic features of acute encephalomyelitis were observed. Viral antigens were mainly detected in neuronal cytoplasm and processes in the different brainstem nuclei and spinal cord, including the anterior and posterior horn cells. Viral antigens were also positive in the nerve roots of spinal cord and autonomic ganglia of intestines. CONCLUSIONS: Our study revealed direct pathologic evidence supporting viral entry into the central nervous system (CNS) through peripheral nerves. In addition to the major motor pathway, EV71 can also enter the CNS via peripheral sensory and autonomic pathways in retrograde axonal transport. PMID- 27357296 TI - Erratum to: Measuring insulin adherence among adults with type 2 diabetes. PMID- 27357278 TI - HIV Genome-Wide Protein Associations: a Review of 30 Years of Research. AB - The HIV genome encodes a small number of viral proteins (i.e., 16), invariably establishing cooperative associations among HIV proteins and between HIV and host proteins, to invade host cells and hijack their internal machineries. As a known example, the HIV envelope glycoprotein GP120 is closely associated with GP41 for viral entry. From a genome-wide perspective, a hypothesis can be worked out to determine whether 16 HIV proteins could develop 120 possible pairwise associations either by physical interactions or by functional associations mediated via HIV or host molecules. Here, we present the first systematic review of experimental evidence on HIV genome-wide protein associations using a large body of publications accumulated over the past 3 decades. Of 120 possible pairwise associations between 16 HIV proteins, at least 34 physical interactions and 17 functional associations have been identified. To achieve efficient viral replication and infection, HIV protein associations play essential roles (e.g., cleavage, inhibition, and activation) during the HIV life cycle. In either a dispensable or an indispensable manner, each HIV protein collaborates with another viral protein to accomplish specific activities that precisely take place at the proper stages of the HIV life cycle. In addition, HIV genome-wide protein associations have an impact on anti-HIV inhibitors due to the extensive cross talk between drug-inhibited proteins and other HIV proteins. Overall, this study presents for the first time a comprehensive overview of HIV genome-wide protein associations, highlighting meticulous collaborations between all viral proteins during the HIV life cycle. PMID- 27357295 TI - Ecological niche modeling of mosquito vectors of West Nile virus in St. John's County, Florida, USA. AB - BACKGROUND: The lack of available vaccines and consistent sporadic transmission of WNV justify the need for mosquito vector control and prediction of their geographic distribution. However, the distribution of WNV transmission is dependent on the mosquito vector and the ecological requirements, which vary from one place to another. METHODS: Presence/density data of two WNV mosquito vectors, Culex nigripalpus and Cx. quinquefasciatus, was extracted within 5 km buffer zones around seropositive records of sentinel chickens in order to delineate their predicting variables and model the habitat suitability of probable infective mosquito using MaxEnt software. Different correlations between density data of the extracted mosquito vectors and 27 climate, land use-land cover, and land surface terrain variables were analyzed using linear regression analysis. Accordingly, the correlated predicting variables were used in building up habitat suitability model for the occurrence records of both mosquito vectors using MaxEnt. RESULTS: The density of both WNV mosquito vectors showed variation in their ecological requirements. Eight predicting variables, out of 27, had significant influence on density of Cx. nigripalpus. Precipitation of driest months was shown to be the best predicting variable for the density of this vector (R (2) = 41.70). Whereas, two variables were proven to predict the distribution of Cx. quinquefasciatus density. Vegetation showed the maximum predicting gain to the density of this mosquito vector (R (2) = 15.74), where nestling birds, in particular exotics, are found. Moreover, Jackknife analysis in MaxEnt demonstrated that urbanization and vegetation data layers significantly contribute in predicting habitat suitability of Cx. nigripalpus and Cx. quinquefasciatus occurrence, respectively, which justifies the contribution of the former in urban and the latter in epizootic transmission cycles of WNV. In addition, habitat suitability risk maps were produced for both vectors in response to their predicting variables. CONCLUSIONS: For the first time in the study area, a quantitative relationship between 27 predicting variables and two WNV mosquito vectors within their foraging habitats was highlighted at the local scale. Accordingly, the predicting variables were used to produce a practical distribution map of probable infective mosquito vectors. This substantially helps in determining where suitable habitats are found. This will potentially help in designing target surveillance and control programmes, saving money, time and man power. However, the suitability risk maps should be updated when serological and entomological data updates are available. PMID- 27357297 TI - Uptake of smoking cessation aids by smokers with a mental illness. AB - Psychiatric inpatient settings represent an opportunity to initiate the provision of tobacco cessation care to smokers with a mental illness. This study describes the use of evidence-based smoking cessation aids proactively and universally offered to a population of psychiatric inpatients upon discharge, and explores factors associated with their uptake. Data derived from the conduct of a randomised controlled trial were analysed in terms of the proportion of participants (N = 378) that utilised cessation aids including project delivered telephone smoking cessation counselling and nicotine replacement therapy (NRT), and Quitline support. Factors associated with uptake of cessation aids were explored using multivariable logistic regression analyses. A large proportion of smokers utilised project delivered cessation counselling calls (89 %) and NRT (79 %), while 11 % used the Quitline. The majority accepted more than seven project delivered telephone cessation counselling calls (52 %), and reported NRT use during more than half of their accepted calls (70 %). Older age, higher nicotine dependence, irregular smoking and seeing oneself as a non-smoker were associated with uptake of behavioural cessation aids. Higher nicotine dependence was similarly associated with use of pharmacological aids, as was NRT use whilst an inpatient. Most smokers with a mental illness took up a proactive offer of aids to support their stopping smoking. Consideration by service providers of factors associated with uptake may increase further the proportion of such smokers who use evidence-based cessation aids and consequently quit smoking successfully. PMID- 27357298 TI - Epidemiological investigation of Middle East respiratory syndrome coronavirus in dromedary camel farms linked with human infection in Abu Dhabi Emirate, United Arab Emirates. AB - The objective of this research was to investigate the prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) infection primarily in dromedary camel farms and the relationship of those infections with infections in humans in the Emirate of Abu Dhabi. Nasal swabs from 1113 dromedary camels (39 farms) and 34 sheep (1 farm) and sputum samples from 2 MERS-CoV-infected camel farm owners and 1 MERS-CoV-infected sheep farm owner were collected. Samples from camels and humans underwent real-time reverse-transcription quantitative PCR screening to detect MERS-CoV. In addition, sequencing and phylogenetic analysis of partially characterized MERS-CoV genome fragments obtained from camels were performed. Among the 40 farms, 6 camel farms were positive for MERS-CoV; the virus was not detected in the single sheep farm. The maximum duration of viral shedding from infected camels was 2 weeks after the first positive test result as detected in nasal swabs and in rectal swabs obtained from infected calves. Three partial camel sequences characterized in this study (open reading frames 1a and 1ab, Spike1, Spike2, and ORF4b) together with the corresponding regions of previously reported MERS-CoV sequence obtained from one farm owner were clustering together within the larger MERS-CoV sequences cluster containing human and camel isolates reported for the Arabian Peninsula. Data provided further evidence of the zoonotic potential of MERS-CoV infection and strongly suggested that camels may have a role in the transmission of the virus to humans. PMID- 27357300 TI - An Experimental and Computational Study on the Effect of Caval Valved Stent Oversizing. AB - Heterotopic implantation of transcatheter tricuspid valve is a new treatment option for tricuspid regurgitation. Transcatheter tricuspid valves are implanted onto the cavoatrial junction in order to avoid the challenging task of anchoring the valve onto the complex tricuspid valve annulus. However, little is known about optimum extent of oversizing of the valved stent in a vena cava. In this study, we implanted valves of the same diameter onto the larger sized inferior vena cava (IVC) and a smaller sized superior vena cava (SVC). The valve in the IVC was oversized by 10.7% while the valve in the SVC was oversized by 21.6%. Finite element analysis was performed (i) to assess the strain on the nitinol stent during manufacturing and deployment; (ii) the stents were deployed in a patient-specific vena cava model and the intramural stress of the vena cava was calculated computationally. These valves were fabricated and placed in a silicone model of a patient-specific right atrium which was part of a mock circulatory system that emulated the patho-physiological flow rate and pressure of a patient with tricuspid regurgitation. Flow measurements were conducted by particle image velocimetry (PIV). It was found that the maximum crimping strain on the nitinol stent was 6.85% which was lower than the critical threshold of 10%. The maximum stress on the vena cava was located at the spot where the hooks met the wall. The maximum stress on the IVC was 0.5098 MPa while the maximum stress on the SVC was 0.7 MPa. The maximum Reynolds shear stress (mRSS) in the vena cava was found to be higher in the IVC than SVC with the highest mRSS being 1741 dynes/cm(2) found in the region of high flow during the peak flow phase. The overtly oversized valve in the SVC did not cause flow disturbances and exhibited mostly laminar flows. The mRSS at the downstream of the vena cava valve and the middle of the atrium remained at low magnitudes. However, velocity fluctuations were high in the IVC in all the time points measured. In conclusion, oversizing the valve may assist anchorage; yet, careful consideration should be taken in choosing the extent of oversizing as it may lead to adverse effects. PMID- 27357299 TI - Endometriomas and deep infiltrating endometriosis in adulthood are strongly associated with anogenital distance, a biomarker for prenatal hormonal environment. AB - STUDY QUESTION: Is the length of the anogenital distance (AGD), a biomarker of the in-utero prenatal hormonal environment, associated with the presence of endometriomas and deep infiltrating endometriosis (DIE)? SUMMARY ANSWER: Shorter AGD is associated with presence of endometriomas and DIE. WHAT IS KNOWN ALREADY: It is debated whether hormonal exposure to estrogens in utero may be a risk factor for endometriosis in adulthood. AGD is a biomarker of prenatal hormonal environment and observational studies have shown an association between AGD and reproductive parameters in both sexes. STUDY DESIGN, SIZE, DURATION: This case control study of 114 women with endometriosis (endometriomas and/or DIE) and 105 controls was conducted between September 2014 and May 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cases were attending the Endometriosis Unit of the Hospital. Prevalent as well as incident cases, diagnosed by transvaginal ultrasound (TVUS), were included. Controls were women without endometriosis attending the gynecological outpatient clinic for routine gynecological exams. Participants completed health questionnaires, followed physical and gynecological examinations, including TVUS. Measurements from the anterior clitoral surface to the upper verge of the anus (AGDAC), and from the posterior fourchette to the upper verge of the anus (AGDAF) were obtained in all subjects. Unconditional multiple logistic regression was used to estimate the association between AGD measurements and presence of endometriomas and/or DIE while accounting for important confounders and covariates, including age, body mass index, vaginal delivery or episiotomy. MAIN RESULTS AND THE ROLE OF CHANCE: AGDAF was related to presence of endometriomas and/or DIE. For all cases of endometriosis (endometriomas and DIE), women in the lowest tertile of the AGDAF distribution, compared with the upper tertile, were 7.6-times (95% CI 2.8-21.0; P trend < 0.001) more likely to have endometriosis. With regard to DIE, women with AGDAF below the median, compared with those with AGDAF above the median, were 41.6-times (95% CI 3.9-438; P-value = 0.002) more likely to have endometriosis. LIMITATIONS, REASONS FOR CAUTION: In case-control studies, information and selection bias has to be ruled out. Physicians conducting the measurement were blind to the status of the patients. Controls came from the same population as the cases. We adjusted for known and suspected confounders and covariates, but the possibility of residual confounding or chance findings should always be considered. As with all observational studies, causal inference is limited. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that endometriosis, especially the DIE, might have a prenatal origin that may be traced back to the hormonal milieu in which the fetus develops. STUDY FUNDING/COMPETING INTEREST: This work was supported by the Ministry of Economy and Competitiveness, ISCIII (AES), grant no. PI13/01237 and the Seneca Foundation, Murcia Regional Agency of Science and Technology, grant no. 19443/PI/14. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable. PMID- 27357301 TI - Modeling Current Density Maps Using Aliev-Panfilov Electrophysiological Heart Model. AB - Most existing studies of cardiac arrhythmia rely on surface measurements through optical or electrical mapping techniques. Current density imaging (CDI) is a method which enables us to study current pathways inside the tissue. However, this method entails implementation complexities for beating ex vivo hearts. Hence, this work presents an approach to simulate and study the current distributions in different cardiac electrophysiological states. The results are corroborated by experimental data, and they indicate that different states were distinguishable. The CDI simulations can be used for studying cardiac arrhythmias under simulation conditions which are otherwise impossible or difficult to be implemented experimentally. PMID- 27357303 TI - Probing Resilience: Daily Environmental Mastery, Self-Esteem, and Stress Appraisal. AB - OBJECTIVES: The current study explores one way the process of resilience arises by investigating the underlying process of stress appraisal. In particular, the analyses examine how resilience resources function each day to attenuate the extent to which life experiences are perceived as threatening, and how trait-like resilience resources shape the appraisal process. METHOD: Daily diary and questionnaire data from 96 participants of Successful Aging in Context: The Macroenvironment and Daily Lived Experience (SAIC; MAge = 67 years, SDAge = 4.9 years; range: 58-86 years) were analyzed using multilevel random coefficient modeling to investigate how individuals' daily perceptions of control and self esteem impacted perceived stress on a given day. RESULTS: Results suggested that both self-esteem and environmental mastery help mitigate the experience of stress; furthermore, dispositional resilience and self-esteem stability predict differences between individuals in the extent to which self-esteem tempers the perception of stress each day. DISCUSSION: The results inform theoretical and empirical work on the nature of resilience, especially regarding how the process arises in ordinary life. From an application perspective, results imply that augmenting environmental mastery and self-esteem, both of which are malleable, can facilitate resilience by helping elders challenge their perceptions of stress each day. PMID- 27357302 TI - [Adverse ocular effects of vaccinations]. AB - Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects. PMID- 27357304 TI - Social Usefulness: Theory and Evidence Concerning a Late Life Identity Construct. AB - PURPOSE OF THE STUDY: To clarify the construct of social usefulness by merging several influential theoretical perspectives on the findings of a qualitative investigation of late life prosociality. DESIGN AND METHODS: In-depth interviews with 20 older adults probed the meaning and psychological significance of the socially useful relationships they maintained with people and organizations. RESULTS: Based on identity theory, the thematic analysis yielded nine classes and more than 100 distinct properties of social usefulness. Self-determination theory was employed to organize and interpret the findings in relation to older adults' needs for relatedness, autonomy, and competence. IMPLICATIONS: Also addressed are the study's implications for multidimensional measurement of social usefulness in future epidemiological and psychosocial studies. PMID- 27357305 TI - What Are Friends for? Friendships and Loneliness Over the Lifespan-From 18 to 79 Years. AB - Preventing and reducing loneliness is crucial to well-being and good health. Social relationships protect people against loneliness. Friendship qualities like intimacy and frequency of contact may vary throughout a person's lifespan. This study explores aspects of friendship and loneliness among people in different age groups: 18 to 29, 30 to 49, 50 to 64, and 65 to 79 years old. Data are from the Norwegian Life Course, Gender and Generations study (N = 14,725). Young people see their friends most often. The proportion of people without confidant friends is higher among older age groups. However, older age groups report higher levels of satisfaction with their contact with friends. Multivariate regression analyses show that the aspiration for contact with friends is more significant to loneliness than actual contact in all age groups. Dissatisfaction with contact with friends is strongly related to loneliness in all age groups. PMID- 27357306 TI - Pitfalls in the synthesis of fluorescent methotrexate oligopeptide conjugates. AB - Methotrexate (MTX) conjugates with poly[Lys(DL-Alam)] based polymeric polypeptides are efficient against Leishmania donovani parasite infection, but the mechanism of the effect is not known yet. We prepared therefore the 5(6) carboxyfluorescein (Cf) labeled oligopeptide [Cf-K(AaAa)] (a: D-alanine, A: L alanine) and the corresponding MTX conjugates [Cf-K(MTX-AaAa)] as model compounds for structure-activity experiments. The conjugate aimed to be synthesized with solid phase methodology on MBHA resin with Boc strategy, using Fmoc-Lys(Boc)-OH. However, various side reactions were identified. Here we report three problems observed during the synthesis as well as solutions developed by us: (1) unexpected cyclopeptide-formation with the lactone-carboxylic group of the Cf was detected, when Cf was attached to the alpha-amino group of the Lys residue on solid phase. This was avoided by changing the order of Cf incorporation with using Fmoc/Dde strategy. Alternatively, we have built the peptide with Fmoc strategy on solid phase first and performed the labeling with Cf-OSu subsequently in solution. (2) During HF cleavage of the protected conjugates, MTX was demonstrated to form adducts with anisole and p-cresol scavengers, and the TMSOTf cleavage methodology was also found to be inadequate due to the large number of side products formed. We report here that using Fmoc/Dde strategy is an appropriate method to circumvent the cleavage with HF or TMSOTf. (3) During the coupling of MTX with oligopeptide, structural and stereo isomers are formed. We have described here the suitable conditions of HPLC separation of these products. PMID- 27357308 TI - Comparison of tissue transglutaminase 2 and bone biological markers osteocalcin, osteopontin and sclerostin expression in human osteoporosis and osteoarthritis. AB - Osteoporosis (OP) and osteoarthritis (OA) are the most common joint diseases, with a high incidence in the elderly population. OP is characterized by trabecular bone remodeling and reabsorption, whereas articular cartilage and subchondral bone remodeling are major features of OA. Although classically considered as independent or even conflicting processes, clinical coexistence of OP and OA was recently described. Transglutaminase 2 (TG2) expression is considered a biomarker of OA, but its role in osteoporotic bone remodeling is still uncertain. We investigated TG2 and bone biological markers (Osteocalcin, Osteopontin, and Sclerostin) in osteoporotic and osteoarthritic osteocartilagineous tissue (n = 54) and human chondrocyte cultures in vitro by immunohistochemistry, immunofluorescence and RT-PCR. Histomorphometric evaluation of bone trabecular remodeling was also performed. In cartilage, TG2 expression was faint in control and OP and significantly less than in OA and OP + OA chondrocytes; the opposite was found for Osteocalcin, whereas Osteopontin and Sclerostin expression was similar. In the subchondral trabecular bone, osteocytes/osteoblasts TG2 expression was slight and similar comparing control, OP, OA, and OP + OA group, whereas Osteocalcin and Osteopontin expression was lower in OP compared to control, OA and OP + OA. Increased TG2 and reduced Osteocalcin expression were maintained in human osteoarthritic chondrocytes in vitro. Histomorphometric analysis confirmed reduced trabecular bone mass in OP and OP + OA compared with OA patients. TG2 represented a suitable biomarker of osteoarthritic chondrocyte activation, whereas osteocalcin and osteopontin characterized osteoporotic osteocyte/osteoblast changes; differences were lost in OP + OA patients, suggesting careful consideration when coexistence of the two diseases occurs. PMID- 27357309 TI - Graph analysis of structural brain networks in Alzheimer's disease: beyond small world properties. AB - Changes in brain connectivity in patients with early Alzheimer's disease (AD) have been investigated using graph analysis. However, these studies were based on small data sets, explored a limited range of network parameters, and did not focus on more restricted sub-networks, where neurodegenerative processes may introduce more prominent alterations. In this study, we constructed structural brain networks out of 87 regions using data from 135 healthy elders and 100 early AD patients selected from the Open Access Series of Imaging Studies (OASIS) database. We evaluated the graph properties of these networks by investigating metrics of network efficiency, small world properties, segregation, product measures of complexity, and entropy. Because degenerative processes take place at different rates in different brain areas, analysis restricted to sub-networks may reveal changes otherwise undetected. Therefore, we first analyzed the graph properties of a network encompassing all brain areas considered together, and then repeated the analysis after dividing the brain areas into two sub-networks constructed by applying a clustering algorithm. At the level of large scale network, the analysis did not reveal differences between AD patients and controls. In contrast, the same analysis performed on the two sub-networks revealed that small worldness diminished with AD only in the sub-network containing the areas of medial temporal lobe known to be heaviest and earliest affected. The second sub-network, which did not present significant AD-induced modifications of 'classical' small world parameters, nonetheless showed a trend towards an increase in small world propensity, a novel metric that unbiasedly quantifies small world structure. Beyond small world properties, complexity and entropy measures indicated that the intricacy of connection patterns and structural diversity decreased in both sub-networks. These results show that neurodegenerative processes impact volumetric networks in a non-global fashion. Our findings provide new quantitative insights into topological principles of structural brain networks and their modifications during early stages of Alzheimer's disease. PMID- 27357307 TI - Targeting the polyamine-hypusine circuit for the prevention and treatment of cancer. AB - The unique amino acid hypusine is present in only two proteins in eukaryotic cells, eukaryotic translation initiation factor 5A-1 (eIF5A1), and eIF5A2, where it is covalently linked to the lysine-50 residue of these proteins via a post translational modification coined hypusination. This unique modification is directed by two highly conserved and essential enzymes, deoxyhypusine synthase (DHPS), and deoxyhypusine hydroxylase (DOHH), which selectively use the polyamine spermidine as a substrate to generate hypusinated eIF5A. Notably, elevated levels of polyamines are a hallmark of most tumor types, and increased levels of polyamines can also be detected in the urine and blood of cancer patients. Further, in-clinic agents that block the function of key biosynthetic enzymes in the polyamine pathway markedly impair tumor progression and maintenance of the malignant state. Thus, the polyamine pathway is attractive as a prognostic, prevention and therapeutic target. As we review, recent advances in our understanding of the specific functions of hypusinated eIF5A and its role in tumorigenesis suggest that the polyamine-hypusine circuit is a high priority target for cancer therapeutics. PMID- 27357310 TI - Small-conductance calcium-activated potassium type 2 channels (SK2, KCa2.2) in human brain. AB - SK2 (KCa2.2) channels are voltage-independent Ca2+-activated K+ channels that regulate neuronal excitability in brain regions important for memory formation. In this study, we investigated the distribution and expression of SK2 channels in human brain by Western blot analysis and immunohistochemistry. Immunoblot analysis of human brain indicated expression of four distinct SK2 channel isoforms: the standard, the long and two short isoforms. Immunohistochemistry in paraffin-embedded post-mortem brain sections was performed in the hippocampal formation, amygdala and neocortex. In hippocampus, SK2-like immunoreactivity could be detected in strata oriens and radiatum of area CA1-CA2 and in the molecular layer. In the amygdala, SK2-like immunoreactivity was highest in the basolateral nuclei, while in neocortex, staining was mainly found enriched in layer V. Activation of SK2 channels is thought to regulate neuronal excitability in brain by contributing to the medium afterhyperpolarization. However, SK2 channels are blocked by apamin with a sensitivity that suggests heteromeric channels. The herein first shown expression of SK2 human isoform b in brain could explain the variability of electrophysiological findings observed with SK2 channels. PMID- 27357311 TI - High-resolution CT of the sternoclavicular joint and first costochondral synchondrosis in asymptomatic individuals. AB - OBJECTIVE: To assess CT features of the sternoclavicular joint (SCJ) and first costochondral junction in asymptomatic patients. MATERIALS AND METHODS: In 66 patients transverse and coronal oblique high-resolution multiple detector CT images of the SCJ and first costochondral junction were obtained. Images were reviewed by consensus of two radiologists. Joint space width was measured at three levels, and osteophytes, geodes, and erosions were evaluated. Variants and degree of ossification were noted. Statistical analysis consisted of Shapiro-Wilk test, Pearson's test, and paired sample t test. RESULTS: There were 34 men and 32 women with a mean age of 60 years (age range, 17-98 years). The width of the joint spaces showed a normal distribution. There was no significant difference between the left and right sides. On coronal images the joint space was wider superiorly and on transverse images posteriorly. There was a trend toward decreasing joint space with age, although it did not reach significance (p > 0.05). Clavicular osteophytes were seen in 16 out of 66 patients (24 %) and sternal osteophytes in 16 out of 66 patients. Clavicular geodes were seen in 10 out of 66 patients (15 %) and sternal geodes in 14 out of 66 patients (14 %). No erosions were seen. Clefts of the first costochondral junction were seen in 31 out of 66 patients (47 %). CONCLUSION: In asymptomatic patients, there is no significant asymmetry of the SCJ. The joint spaces did not significantly decrease with age, although such a trend could be observed. Pronounced joint space narrowing with large geodes and osteophytes was not seen. Clefts of the first costochondral junction are common and not significant. PMID- 27357312 TI - Subcutaneous extraskeletal osteosarcoma of the forearm: a case report and review of the literature. AB - Extraskeletal osteosarcoma (ESOS) originating in the subcutaneous tissue is a rare occurrence, accounting for less than 10 % of ESOS cases. Osteosarcoma of extraskeletal origin accounts for approximately 2-4 % of all osteosarcomas, and 1 % of soft tissue sarcomas. We report a case of an 80-year-old female with an isolated primary subcutaneous tumor of the forearm. After imaging, surgical excision, and pathological analysis, the diagnosis of a subcutaneous osteosarcoma was made. This report documents the clinical and pathological findings of subcutaneous ESOS in this case, along with a review of previous cases of subcutaneous ESOS. PMID- 27357313 TI - The Kidney: An Organ in the Front Line of Oxidative Stress-Associated Pathologies. AB - Both acute kidney injury (AKI) and chronic kidney disease (CKD) are major causes of renal failure in humans and are associated with high incidences of morbidity and mortality rates. AKI and CKD are closely interconnected, and fueled by the obesity and diabetes epidemic, their prevalence is alarmingly increasing to the point that it currently represents a major heath issue worldwide. The kidney is an organ that is particularly sensitive to redox imbalance, resulting in excessive production of reactive oxygen species. Oxidative stress is viewed as a critical pathogenic factor implicated in the initiation, development, and progression of most renal diseases. This Forum discusses the redox-dependent factors and mechanisms accounting for the perturbation of renal function and circulation in the context of the major kidney pathologies linked to hypertension, diabetes, and cancer. Antioxid. Redox Signal. 25, 639-641. PMID- 27357314 TI - S100A1 transgenic treatment of acute heart failure causes proteomic changes in rats. AB - S100 Ca2+-binding protein A1 (S100A1) is an important regulator of myocardial contractility. The aim of the present study was to identify the underlying mechanisms of S100A1 activity via profiling the protein expression in rats administered with an S100A1 adenovirus (Ad-S100A1-EGFP) following acute myocardial infarction (AMI). LTQ OrbiTrap mass spectrometry was used to profile the protein expression in the Ad-S100A1-EGFP and control groups post-AMI. Using Protein Analysis Through Evolutionary Relationships (PANTHER) analysis, 134 energy metabolism-associated proteins, which comprised 20 carbohydrate metabolism associated and 27 lipid metabolism associated proteins, were identified as differentially expressed in the Ad-S100A1-EGFP hearts compared with controls. The majority of the differentially expressed proteins identified were important enzymes involved in energy metabolism. The present study identified 12 Ca2+ binding proteins and 22 cytoskeletal proteins. The majority of the proteins expressed in the Ad-S100A1-EGFP group were upregulated compared with the control group. These results were further validated using western blot analysis. Following AMI, Ca2+ is crucial for the recovery of myocardial function in S100A1 transgenic rats as indicated by the upregulation of proteins associated with energy metabolism and Ca2+-binding. Thus, the current study ascertained that energy production and contractile ability were enhanced after AMI in the ventricular myocardium of the Ad-S100A1-EGFP group. PMID- 27357315 TI - Evaluation of preferences of women and healthcare professionals in Singapore for implementation of noninvasive prenatal testing for Down syndrome. AB - INTRODUCTION: Invasive prenatal diagnosis (IPD) has long been used to prenatally diagnose Down syndrome (DS), but it is associated with a small risk of miscarriage. Noninvasive prenatal testing (NIPT) is a highly sensitive screening test using cell-free DNA in maternal blood for detection of DS without the risk of miscarriage, but it confers a small risk of false-positive and false-negative results. The implementation of these procedures into clinical practice requires an understanding of stakeholder preferences. METHODS: A total of 69 health professionals (HPs) and 301 women took part in a discrete choice experiment (DCE) in which preferences for four prenatal test attributes - accuracy, time of results, risk of miscarriage and amount of information provided - were assessed. Conditional logit regression was used to analyse the data. Data on demographics and ranked preferences for test attributes was collected, and a direct choice question regarding NIPT, IPD or neither test was posed to participants. RESULTS: The women showed a preference for test safety, whereas HPs prioritised test accuracy above all other attributes. When offered a direct choice of NIPT, IPD or neither test, women aged 35 years and older, those with previous miscarriage or who knew a child with DS were more likely to choose NIPT. Chinese women preferred NIPT, whereas Indian women preferred IPD. CONCLUSION: Our data highlights the need for patient-specific counselling, taking into account previous experiences and cultural factors. Since women and HPs prioritise different test attributes, it is essential that HPs recognise these differences in order to provide non biased counselling. PMID- 27357316 TI - Prognostic factors for candidaemia in intensive care unit patients: a retrospective analysis. AB - INTRODUCTION: Candidaemia, recognised as a fairly common disease among intensive care unit (ICU) patients, carries a poor prognosis. However, as studies on the prognostic factors associated with candidaemia in ICU patients are limited, this study aimed to establish the best prognostic factor for ICU patients with candidaemia in a tertiary care hospital in Japan. METHODS: We conducted a retrospective cohort study of patients with candidaemia in the emergency ICU at Fukuoka University Hospital, Fukuoka, Japan, from April 2010 to March 2015. Demographic and clinical data was collected from the patients' medical records and laboratory databases. RESULTS: A total of 25 patients were included in the study. However, 18 patients died during hospitalisation, resulting in an in hospital mortality rate of 72.0%. The variables of Sequential Organ Failure Assessment (SOFA) score and cumulative number of risk factors for invasive candidiasis showed significant differences between patients in the survivor and non-survivor groups (p < 0.05). The areas under the receiver operating characteristic curves for the SOFA score and cumulative number of risk factors for invasive candidiasis were 0.873 (95% confidence interval [CI] 0.72-1.00) and 0.937 (95% CI 0.84-1.00), respectively. CONCLUSION: Our results suggest that the cumulative number of risk factors for invasive candidiasis was the most useful prognostic indicator for candidaemia in ICU patients. PMID- 27357317 TI - Efficacy and patient satisfaction with incobotulinumtoxinA for the treatment of glabellar frown lines. AB - INTRODUCTION: This study describes the physician experience relating to the effectiveness of incobotulinumtoxinA and patient satisfaction with its use for the treatment of glabellar frown lines (GFLs). METHODS: A total of 17 patients from six dermatological clinics, aged > 18 years and with mild to very severe GFLs at maximum frown, were included. Patients were excluded if they had treatment with resorbable fillers and botulinum toxins in the preceding six months, or non-resorbable fillers or surgery in the treatment area. Injection sites (range 3-5) were chosen depending on their severity (dose range 12-20 U), covering corrugators and procerus muscles. Physicians assessed improvements to GFLs using the Merz scale on Days 4 and 14 after treatment. Patients completed a self-reported questionnaire on their facial wrinkles on Days 2 and 4 after treatment. RESULTS: Most (76.5%) patients were women. The mean age of the patients was 46.9 +/- 10.0 years. Mean severities (on the Merz scale) for at-rest and dynamic (with expression) GFLs at baseline were 1.3 +/- 1.10 and 3.4 +/- 0.38, respectively, and decreased on Day 14 (p < 0.05). Treatment response rates (> 1-point improvement) for at-rest and dynamic (with expression) GFLs on Day 4 were 40% and 100%, respectively. All patients reported being satisfied or very satisfied, and 64.3%-71.4% indicated that their facial wrinkles had improved on Day 2. CONCLUSION: IncobotulinumtoxinA was fast acting with visible improvements by Day 4 and all patients expressed satisfaction with their treatment after two days. GFLs saw the most improvement among the facial characteristics measured. PMID- 27357318 TI - Pathological findings in a case of bone marrow carcinosis due to gastric cancer complicated by disseminated intravascular coagulation and thrombotic microangiopathy. AB - An 80-year-old man was diagnosed with disseminated intravascular coagulation (DIC) and thrombotic microangiopathy (TMA) associated with mucin-producing gastric cancer with bone marrow metastasis. He died suddenly on the third day of hospitalization before chemotherapy. Microscopic autopsy findings revealed fibrin thrombi by phosphotungstic acid hematoxylin (PTAH) staining of the renal glomeruli, and platelet thrombi by von Willebrand Factor (Factor VIII Antigen) staining of the microvessels of the bleeding intestine. Tumor cells were negative for both stains. Staining of endothelial cells (EC) of the small vessels with thrombomodulin (TM) stain revealed destruction of EC structure. This patient was thought to have had systemic dissemination of solid tumor cells associated with DIC and TMA, the clinical course of which is extremely aggressive. Different types of thrombi were observed in different organs, such as the kidneys and small intestine, which supported the co-occurrence of DIC and TMA by microscopic pathological findings. These findings provide pathological evidence for the pathology of the concurrent development of DIC and TMA and show differences in the types of thrombi according to the blood vessel localization. Furthermore, the findings were highly suggestive of the mechanisms causing organ dysfunction, such as renal dysfunction, and gastrointestinal bleeding. PMID- 27357319 TI - Effect of anti-biofilm glass-ionomer cement on Streptococcus mutans biofilms. AB - Dental restorative materials with antimicrobial properties can inhibit bacterial colonization, which may result in a reduction of caries at tooth-filling interaction zones. This study aimed to develop antibacterial glass-ionomer cements (GIC) containing a quaternary ammonium monomer (dimethylaminododecyl methacrylate, DMADDM), and to investigate their effect on material performance and antibacterial properties. Different mass fractions (0, 1.1% and 2.2%) of DMADDM were incorporated into the GIC. The flexure strength, surface charge density, surface roughness and fluoride release were tested. A Streptococcus mutans biofilm model was used. Exopolysaccharides (EPS) staining was used to analyze the inhibitory effect of DMADDM on the biofilm matrix. In addition, biofilm metabolic activity, lactic acid metabolism and the expression of glucosyltransferase genes gtfB, gtfC and gtfD were measured. GIC containing 1.1% and 2.2% DMADDM had flexural strengths matching those of the commercial control (P>0.1). DMADDM was able to increase the surface charge density but reduced surface roughness (P<0.05). The incorporation of 1.1% and 2.2% DMADDM elevated the release of fluoride by the GIC in the first 2 days (P<0.05). The novel DMADDM modified GIC significantly reduced biofilm metabolic activity (P<0.05) and decreased lactic acid production (P<0.05). The quantitative polymerase chain reaction (qPCR) results showed that the expression of gtfB, gtfC and gtfD decreased when mass fractions of DMADDM increased (P<0.05). EPS staining showed that both the bacteria and EPS in biofilm decreased in the DMADDM groups. The incorporation of DMADDM could modify the properties of GIC to influence the development of S. mutans biofilms. In this study, we investigated the interface properties of antibacterial materials for the first time. GIC containing DMADDM can improve material performance and antibacterial properties and may contribute to the better management of secondary caries. PMID- 27357320 TI - Phenotypic research on senile osteoporosis caused by SIRT6 deficiency. AB - Osteoporosis is a serious public bone metabolic disease. However, the mechanisms underlying bone loss combined with ageing, which is known as senile osteoporosis, remains unknown. Here we show the detailed phenotype of this disease caused by SIRT6 knock out (KO) in mice. To the best of our knowledge, this is the first study to reveal that SIRT6 is expressed in both bone marrow stroma cells and bone related cells in both mouse and human models, which suggests that SIRT6 is an important regulator in bone metabolism. SIRT6-KO mice exhibit a significant decrease in body weight and remarkable dwarfism. The skeleton of the SIRT6-KO mouse is deficient in cartilage and mineralized bone tissue. Moreover, the osteocalcin concentration in blood is lower, which suggests that bone mass is markedly lost. Besides, the tartrate-resistant acid phosphatase 5b (TRAP5b) concentration is much higher, which suggests that bone resorption is overactive. Both trabecular and cortical bones exhibit severe osteopenia, and the bone mineral density is decreased. Moreover, double-labelling analysis shows that bone formation is much slower. To determine whether SIRT6 directly regulates bone metabolism, we cultured primary bone marrow stromal cells for osteogenesis and osteoclastogenesis separately to avoid indirect interference in vivo responses such as inflammation. Taken together, these results show that SIRT6 can directly regulate osteoblast proliferation and differentiation, resulting in attenuation in mineralization. Furthermore, SIRT6 can directly regulate osteoclast differentiation and results in a higher number of small osteoclasts, which may be related to overactive bone resorption. PMID- 27357321 TI - Human enamel thickness and ENAM polymorphism. AB - The tooth enamel development gene, enamelin (ENAM), showed evidence of positive selection during a genome-wide scan of human and primate DNA for signs of adaptive evolution. The current study examined the hypothesis that a single nucleotide polymorphism (SNP) C14625T (rs7671281) in the ENAM gene identified in the genome-wide scan is associated with a change in enamel phenotype. African Americans were selected as the target population, as they have been reported to have a target SNP frequency of approximately 50%, whereas non-Africans are predicted to have a 96% SNP frequency. Digital radiographs and DNA samples from 244 teeth in 133 subjects were analysed, and enamel thickness was assessed in relation to SNP status, controlling for age, sex, tooth number and crown length. Crown length was found to increase with molar number, and females were found to have thicker enamel. Teeth with larger crowns also had thicker enamel, and older subjects had thinner enamel. Linear regression and generalized estimating equations were used to investigate the relationship between enamel thickness of the mandibular molars and ENAM SNP status; enamel in subjects with the derived allele was significantly thinner (P=0.040) when the results were controlled for sex, age, tooth number and crown length. The derived allele demonstrated a recessive effect on the phenotype. The data indicate that thinner dental enamel is associated with the derived ENAM genotype. This is the first direct evidence of a dental gene implicated in human adaptive evolution as having a phenotypic effect on an oral structure. PMID- 27357322 TI - TET1 knockdown inhibits the odontogenic differentiation potential of human dental pulp cells. AB - Human dental pulp cells (hDPCs) possess the capacity to differentiate into odontoblast-like cells and generate reparative dentin in response to exogenous stimuli or injury. Ten-eleven translocation 1 (TET1) is a novel DNA methyldioxygenase that plays an important role in the promotion of DNA demethylation and transcriptional regulation in several cell lines. However, the role of TET1 in the biological functions of hDPCs is unknown. To investigate the effect of TET1 on the proliferation and odontogenic differentiation potential of hDPCs, a recombinant shRNA lentiviral vector was used to knock down TET1 expression in hDPCs. Following TET1 knockdown, TET1 was significantly downregulated at both the mRNA and protein levels. Proliferation of the hDPCs was suppressed in the TET1 knockdown groups. Alkaline phosphatase activity, the formation of mineralized nodules, and the expression levels of DSPP and DMP1 were all reduced in the TET1-knockdown hDPCs undergoing odontogenic differentiation. Based on these results, we concluded that TET1 knockdown can prevent the proliferation and odontogenic differentiation of hDPCs, which suggests that TET1 may play an important role in dental pulp repair and regeneration. PMID- 27357324 TI - Articulated dental cast analysis of asymptomatic and symptomatic populations. AB - Dental instrumentation has long provided insight into the mechanism of musculo skeletal function of the gnathic system. While large population studies associate dental arch displacement (DAD), especially laterally, with symptoms, mandibular condyle displacement (CD) resulting from DAD has not been targeted as possibly etiologic in the production of common muscle contraction headache (CMCH) and temporo-mandibular dysfunction (TMD). The objective was to evaluate the three dimensional nature of DAD and CD between the seated condylar position (SCP) and the intercuspal position (ICP) and to compare results derived from large deprogrammed asymptomatic and symptomatic populations. A total of 1 192 sets of dental casts collected from asymptomatic and symptomatic populations were articulated in the SCP. The initial occlusal contact, DAD, and condylar displacement were evaluated for frequency, direction, and magnitude of displacement between the SCP and ICP. The data revealed significant displacement between the SCP and ICP of the condyles (displaced most frequently inferior (down) and posterior (distal)) and substantially increased frequency and magnitude of displacement of the dental arches (with posterior premature occlusal contacts, increased overjet, decreased overbite, midline differences, and occlusal classification changes) in symptomatic subjects. These discrepancies were statistically significant and clinically significant. The data support the concept of increased DAD and CD with dysfunction. Transverse condylar displacement, commonly presenting with dental cross bite, may be associated with CMCH and TMD. Displacement of the mandibular condyle may be an etiologic factor in CMCH and dysfunction of the temporo-mandibular joint. PMID- 27357325 TI - Role of GLTSCR2 in the regulation of telomerase activity and chromosome stability. AB - Telomerase is essential for regulating telomeres, and its activation is a critical step in cellular immortalization and tumorigenesis. The transcriptional activation of human telomerase reverse transcriptase (hTERT) is critical for telomerase expression. Although several transcriptional activators have been identified, factors responsible for enhancing the hTERT promoter remain to be fully elucidated. In the present study, the role of glioma tumor-suppressor candidate region gene 2 (GLTSCR2) in telomerase regulation was analyzed. A doxycyclin-inducible green fluorescent protein (GFP)-tagged GLTSCR2-expressing adenovirus (Ad-GLT/GFP) was used for the transduction of SK-Hep-1 and T98G cancer cells, and normal human umbilical vein endothelial cells. Changes in telomerase activity using telomere repeat amplification protocol assay were assessed, and the gene expression levels of hTERT were then examined. To investigate chromosome instability and senescence, Giemsa and beta-galactosidase staining was performed. The results revealed that overexpression of GLTSCR2 significantly increased telomerase activity in the cancer and normal cell lines. This increase was consistent with increases in the protein and mRNA expression levels of hTERT. In luciferase assays, the hTERT promoter was activated by GLTSCR2. Knockdown of GLTSCR2 led to the downregulation of telomerase activity, abnormal nuclear morphology as a marker of chromosome instability, significant suppression of growth rate, alterations in cellular morphology and, eventually, cellular senescence. Taken together, the results of the present study suggested that GLTSCR2 is crucially involved in the positive regulation of telomerase and chromosome stability. PMID- 27357323 TI - The effect of platform switching on the levels of metal ion release from different implant-abutment couples. AB - The improved peri-implant bone response demonstrated by platform switching may be the result of reduced amounts of metal ions released to the surrounding tissues. The aim of this study was to compare the levels of metal ions released from platform-matched and platform-switched implant-abutment couples as a result of accelerated corrosion. Thirty-six titanium alloy (Ti-6Al-4V) and cobalt-chrome alloy abutments were coupled with titanium cylinders forming either platform switched or platform-matched groups (n=6). In addition, 18 unconnected samples served as controls. The specimens were subjected to accelerated corrosion by static immersion in 1% lactic acid for 1 week. The amount of metal ions ion of each test tube was measured using inductively coupled plasma mass spectrometry. Scanning electron microscope (SEM) images and energy dispersive spectroscopy X ray analyses were performed pre- and post-immersion to assess corrosion at the interface. The platform-matched groups demonstrated higher ion release for vanadium, aluminium, cobalt, chrome, and molybdenum compared with the platform switched groups (P<0.05). Titanium was the highest element to be released regardless of abutment size or connection (P<0.05). SEM images showed pitting corrosion prominent on the outer borders of the implant and abutment platform surfaces. In conclusion, implant-abutment couples underwent an active corrosion process resulting in metal ions release into the surrounding environment. The highest amount of metal ions released was recorded for the platform-matched groups, suggesting that platform-switching concept has a positive effect in reducing the levels of metal ion release from the implant-abutment couples. PMID- 27357326 TI - Automated Video Detection of Epileptic Convulsion Slowing as a Precursor for Post Seizure Neuronal Collapse. AB - Automated monitoring and alerting for adverse events in people with epilepsy can provide higher security and quality of life for those who suffer from this debilitating condition. Recently, we found a relation between clonic slowing at the end of a convulsive seizure (CS) and the occurrence and duration of a subsequent period of postictal generalized EEG suppression (PGES). Prolonged periods of PGES can be predicted by the amount of progressive increase of interclonic intervals (ICIs) during the seizure. The purpose of the present study is to develop an automated, remote video sensing-based algorithm for real-time detection of significant clonic slowing that can be used to alert for PGES. This may help preventing sudden unexpected death in epilepsy (SUDEP). The technique is based on our previously published optical flow video sequence processing paradigm that was applied for automated detection of major motor seizures. Here, we introduce an integral Radon-like transformation on the time-frequency wavelet spectrum to detect log-linear frequency changes during the seizure. We validate the automated detection and quantification of the ICI increase by comparison to the results from manually processed electroencephalography (EEG) traces as "gold standard". We studied 48 cases of convulsive seizures for which synchronized EEG video recordings were available. In most cases, the spectral ridges obtained from Gabor-wavelet transformations of the optical flow group velocities were in close proximity to the ICI traces detected manually from EEG data during the seizure. The quantification of the slowing-down effect measured by the dominant angle in the Radon transformed spectrum was significantly correlated with the exponential ICI increase factors obtained from manual detection. If this effect is validated as a reliable precursor of PGES periods that lead to or increase the probability of SUDEP, the proposed method would provide an efficient alerting device. PMID- 27357328 TI - Has there been a shift in alcohol-related violence to neighbouring inner city 'lockout law' exclusion areas in Sydney? PMID- 27357329 TI - Arthroplasty for tenosynovial giant cell tumors. AB - Background and purpose - Tenosynovial giant cell tumors (t-GCTs) can behave aggressively locally and affect joint function and quality of life. The role of arthroplasty in the treatment of t-GCT is uncertain. We report the results of arthroplasty in t-GCT patients. Patients and methods - t-GCT patients (12 knee, 5 hip) received an arthroplasty between 1985 and 2015. Indication for arthroplasty, recurrences, complications, quality of life, and functional scores were evaluated after a mean follow-up time of 5.5 (0.2-15) years. Results - 2 patients had recurrent disease. 2 other patients had implant loosening. Functional scores showed poor results in almost half of the knee patients. 4 of the hip patients scored excellent and 1 scored fair. Quality of life was reduced in 1 or more subscales for 2 hip patients and for 5 knee patients. Interpretation - In t-GCT patients with extensive disease or osteoarthritis, joint arthroplasty is an additional treatment option. However, recurrences, implant loosening, and other complications do occur, even after several years. PMID- 27357327 TI - Coronary CT angiography with 80 kV tube voltage and low iodine concentration contrast agent in patients with low body weight. AB - BACKGROUND: Coronary CT angiography (CTA) is gaining widespread acceptance for the non-invasive evaluation of coronary arteries. However, radiation exposure and administration of iodinated contrast agents are still reasons of some concern. The 80 kV tube voltage increases the attenuation of iodine, allowing to use lower iodine concentration contrast agents for coronary CTA. OBJECTIVE: We evaluated the diagnostic accuracy of coronary CTA performed with 64-slice scanner, 80 kV tube voltage, iterative reconstruction algorithm and ultra-low concentration contrast medium to reduce iodine load and radiation dose. METHODS: We enrolled 45 patients with low body weight and indication for elective invasive coronary angiography (ICA). All patients received an 80 ml bolus of Iodixanol-270 at an infusion rate of 5 mL/s and underwent coronary CTA (80 kV and 500-550 mA) with prospective ECG-triggering. Image quality score, type of artifacts, coronary CTA evaluability, diagnostic accuracy and radiation exposure were assessed. RESULTS: Pre-test probability of CAD was low-to-intermediate (48%). Accordingly, the prevalence of obstructive CAD was 47% (21 out of 45 patients). Most (93%) of the patients were pre-treated with intravenous metoprolol before scanning and achieved a heart rate suitable for prospective ECG-triggering coronary CTA (53 +/ 3 bpm). The mean effective dose and iodine load were 1.1 +/- 0.4 mSv and 21.6 gI, respectively. We rated 443 out of 720 coronary segments as being of excellent image quality. In a segment-based model, coronary evaluability (number of coronary segments evaluable/total number of coronary segments), was 97% (699/720 segments). In a segment-based analysis, sensitivity, specificity, positive predictive value, negative predictive value and accuracy for >50% coronary stenosis identification vs. ICA were 89%, 99%, 89%, 99% and 99%, respectively. In a patient-based analysis, sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 94%, 89%, 83%, 96% and 91%, respectively. CONCLUSIONS: In patients with low body weight, image quality and diagnostic accuracy of ultra-low radiation dose and low-iodine load coronary CTA are good and similar to values reported in the literature for standard tube voltage and iodine load protocols. PMID- 27357330 TI - Two-Step Physical Deposition of a Compact CuI Hole-Transport Layer and the Formation of an Interfacial Species in Perovskite Solar Cells. AB - A simple and practical approach is introduced for the deposition of CuI as an inexpensive inorganic hole-transport material (HTM) for the fabrication of low cost perovskite solar cells (PSCs) by gas-solid phase transformation of Cu to CuI. The method provides a uniform and well-controlled CuI layer with large grains and good compactness that prevents the direct connection between the contact electrodes. Solar cells prepared with CuI as the HTM with Au electrodes displays an exceptionally high short-circuit current density of 32 mA cm(-2) , owing to an interfacial species formed between the perovskite and the Cu resulting in a long wavelength contribution to the incident photon-to-electron conversion efficiency (IPCE), and an overall power conversion efficiency (PCE) of 7.4 %. The growth of crystalline and uniform CuI on a low roughness perovskite layer leads to remarkably high charge extraction in the cells, which originates from the high hole mobility of CuI in addition to a large number of contact points between CuI and the perovskite layer. In addition, the solvent-free method has no damaging side effect on the perovskite layer, which makes it an appropriate method for large scale applications of CuI in perovskite solar cells. PMID- 27357332 TI - Regional Clinical Alliance Path and Cardiac Rehabilitation After Hospital Discharge for Acute Myocardial Infarction Patients in Japan - A Nationwide Survey. AB - BACKGROUND: The regional clinical alliance path (RCAP) after discharge from an acute-phase hospital is emerging as a tool for bridging acute-phase treatment and chronic-phase disease management. However, the optimal application of RCAP for acute myocardial infarction (AMI) remains unknown in Japan, and therefore a nationwide survey of hospitals was conducted. METHODS AND RESULTS: In 2009, questionnaires were sent to 1,240 cardiology training hospitals authorized by the Japanese Circulation Society. The response rate was 62.9% (780/1,240). Of the 780 responding hospitals, 708 treated AMI, and in these hospitals the number of AMI patients and percutaneous coronary intervention (PCI) procedures performed were, respectively, 59+/-52 and 200+/-206 per year. The implementation rate of emergency PCI was high (91%), but that of outpatient cardiac rehabilitation (OPCR) was very low (18%). The implementation rate of RCAP after AMI was significantly lower (10%) than after stroke (57%). Cardiac rehabilitation (CR) was adopted as part of RCAP in only 19% (13/70) of currently operating RCAP programs. CONCLUSIONS: This first Japanese nationwide survey of RCAP after AMI showed that in contrast to the broad dissemination of acute-phase invasive treatment for AMI, there was infrequent implementation of OPCR, RCAP after AMI, and RCAP including CR. It will be necessary to broaden the use of RCAP after AMI, including OPCR. (Circ J 2016; 80: 1750-1755). PMID- 27357333 TI - Safety and Efficacy of Cryoballoon Ablation for Paroxysmal Atrial Fibrillation in Japan - Results From the Japanese Prospective Post-Market Surveillance Study. AB - BACKGROUND: Outcomes of cryoballoon ablation for paroxysmal atrial fibrillation (PAF) have been reported in the Western countries but not in Japan. The CRYO Japan PMS study was a single-arm, observational, multicenter, prospective study of the 2nd-generation cryoballoon Arctic Front Advance(TM). We evaluated device- and procedure-related complications and clinical outcomes at 6 months. METHODS AND RESULTS: The 616 patients (male, 72%; mean age, 63+/-11 years) were enrolled from 33 Japanese hospitals. Of all patients, 610 had PAF, and procedural data were analyzed in 607. A subset of 328 patients was followed for 6 months for the primary efficacy analysis. AF recurrence outside the 3-month blanking period or repeat ablation was considered treatment failure. Pulmonary vein isolation was achieved in 606/607 patients (99.8%); 1 patient (0.3%) had a repeat ablation during the blanking period. Freedom from AF at 6 months was 88.4% (95% CI: 84.1 91.6%). Device- and/or procedure-related adverse events included phrenic nerve injury unresolved at hospital discharge in 9/616 patients (1.5%), which resolved within 6 months in 7, pericardial effusion in 5/616 (0.8%), and tamponade in 4/616 (0.6%). One non-device-related death from pneumonia was reported 6 days post-procedure. CONCLUSIONS: Cryoballoon ablation is safe and effective for Japanese PAF patients, with 88.4% AF freedom at 6 months post-ablation. (Circ J 2016; 80: 1744-1749). PMID- 27357334 TI - Hyperuricemia Plays Pivotal Role in Progression of Kidney Disease. PMID- 27357335 TI - pH and concentration dependence of the optical properties of thiol-capped CdTe nanocrystals in water and D2O. AB - The optical properties of semiconductor nanocrystals (SC NCs) are largely controlled by their size and surface chemistry, i.e., the chemical composition and thickness of inorganic passivation shells and the chemical nature and number of surface ligands as well as the strength of their bonds to surface atoms. The latter is particularly important for CdTe NCs, which - together with alloyed CdxHg1-xTe - are the only SC NCs that can be prepared in water in high quality without the need for an additional inorganic passivation shell. Aiming at a better understanding of the role of stabilizing ligands for the control of the application-relevant fluorescence features of SC NCs, we assessed the influence of two of the most commonly used monodentate thiol ligands, thioglycolic acid (TGA) and mercaptopropionic acid (MPA), on the colloidal stability, photoluminescence (PL) quantum yield (QY), and PL decay behavior of a set of CdTe NC colloids. As an indirect measure for the strength of the coordinative bond of the ligands to SC NC surface atoms, the influence of the pH (pD) and the concentration on the PL properties of these colloids was examined in water and D2O and compared to the results from previous dilution studies with a set of thiol-capped Cd1-xHgxTe SC NCs in D2O. As a prerequisite for these studies, the number of surface ligands was determined photometrically at different steps of purification after SC NC synthesis with Ellman's test. Our results demonstrate ligand control of the pH-dependent PL of these SC NCs, with MPA-stabilized CdTe NCs being less prone to luminescence quenching than TGA-capped ones. For both types of CdTe colloids, ligand desorption is more pronounced in H2O compared to D2O, underlining also the role of hydrogen bonding and solvent molecules. PMID- 27357337 TI - Prognosis of cerebral lipiodol embolism caused by transarterial chemoembolization. AB - OBJECTIVES: Transarterial chemoembolization (TACE) plays an essential role in the management of unresectable hepatocellular cell carcinoma and other hepatic neoplasms. Cerebral lipiodol embolism (CLE) is a rare complication of TACE and its prognostic factors have not been well studied. The aim of this paper was to elucidate the prognostic factors of CLE based on clinical data obtained from our patients and cases published since 2004. METHODS: We present two patients with CLE, analyze the clinical data, and review all CLE cases published since 2004. A poor outcome was defined as stupor, coma, quadriplegia, or death within 45 days. Patients who had other neurological conditions within 45 days were considered as having a good outcome. RESULTS: The rate of poor outcome was 25.7% (9/35). Compared with the patients with good outcome, those with poor outcome were older (mean age 68.3 +/- 7.3 vs. 58.3 +/- 10.6 years, p = 0.03), more often female (76.9% vs. male 33.3%, p = 0.02), and more likely chemoembolized via both the right hepatic and right inferior phrenic arteries (44.4 vs. 8.7%, p = 0.02). DISCUSSION: The prognosis of CLE was related to age, gender, and the arteries selected for injection. PMID- 27357336 TI - Insights into Campylobacter jejuni colonization and enteritis using a novel infant rabbit model. AB - A lack of relevant disease models for Campylobacter jejuni has long been an obstacle to research into this common enteric pathogen. Here we used an infant rabbit to study C. jejuni infection, which enables us to define several previously unknown but key features of the organism. C. jejuni is capable of systemic invasion in the rabbit, and developed a diarrhea symptom that mimicked that observed in many human campylobacteriosis. The large intestine was the most consistently colonized site and produced intestinal inflammation, where specific cytokines were induced. Genes preferentially expressed during C. jejuni infection were screened, and acs, cj1385, cj0259 seem to be responsible for C. jejuni invasion. Our results demonstrates that the infant rabbit can be used as an alternative experimental model for the study of diarrheagenic Campylobacter species and will be useful in exploring the pathogenesis of other related pathogens. PMID- 27357338 TI - The multicellularity genes of dictyostelid social amoebas. AB - The evolution of multicellularity enabled specialization of cells, but required novel signalling mechanisms for regulating cell differentiation. Early multicellular organisms are mostly extinct and the origins of these mechanisms are unknown. Here using comparative genome and transcriptome analysis across eight uni- and multicellular amoebozoan genomes, we find that 80% of proteins essential for the development of multicellular Dictyostelia are already present in their unicellular relatives. This set is enriched in cytosolic and nuclear proteins, and protein kinases. The remaining 20%, unique to Dictyostelia, mostly consists of extracellularly exposed and secreted proteins, with roles in sensing and recognition, while several genes for synthesis of signals that induce cell type specialization were acquired by lateral gene transfer. Across Dictyostelia, changes in gene expression correspond more strongly with phenotypic innovation than changes in protein functional domains. We conclude that the transition to multicellularity required novel signals and sensors rather than novel signal processing mechanisms. PMID- 27357339 TI - Discovery and Description of Ebola Zaire Virus in 1976 and Relevance to the West African Epidemic During 2013-2016. AB - BACKGROUND: In 1976, the first cases of Ebola virus disease in northern Democratic Republic of the Congo (then referred to as Zaire) were reported. This article addresses who was responsible for recognizing the disease; recovering, identifying, and naming the virus; and describing the epidemic. Key scientific approaches used in 1976 and their relevance to the 3-country (Guinea, Sierra Leone, and Liberia) West African epidemic during 2013-2016 are presented. METHODS: Field and laboratory investigations started soon after notification, in mid-September 1976, and included virus cell culture, electron microscopy (EM), immunofluorescence antibody (IFA) testing of sera, case tracing, containment, and epidemiological surveys. In 2013-2016, medical care and public health work were delayed for months until the Ebola virus disease epidemic was officially declared an emergency by World Health Organization, but research in pathogenesis, clinical presentation, including sequelae, treatment, and prevention, has increased more recently. RESULTS: Filoviruses were cultured and observed by EM in Antwerp, Belgium (Institute of Tropical Medicine); Porton Down, United Kingdom (Microbiological Research Establishment); and Atlanta, Georgia (Centers for Disease Control and Prevention). In Atlanta, serological testing identified a new virus. The 1976 outbreak (280 deaths among 318 cases) stopped in <11 weeks, and basic clinical and epidemiological features were defined. The recent massive epidemic during 2013-2016 (11 310 deaths among 28 616 cases) has virtually stopped after >2 years. Transmission indices (R0) are higher in all 3 countries than in 1976. CONCLUSIONS: An international commission working harmoniously in laboratories and with local communities was essential for rapid success in 1976. Control and understanding of the recent West African outbreak were delayed because of late recognition and because authorities were overwhelmed by many patients and poor community involvement. Despite obstacles, research was a priority in 1976 and recently. PMID- 27357341 TI - Possibilities for Immunomodulation in Congenital Toxoplasmosis. PMID- 27357340 TI - Protection of Humanized Mice From Repeated Intravaginal HIV Challenge by Passive Immunization: A Model for Studying the Efficacy of Neutralizing Antibodies In Vivo. AB - Humanized mice reconstituted with a human immune system can be mucosally infected with human immunodeficiency virus (HIV), opening up the possibility of studying HIV transmission in a small-animal model. Here we report that passive immunization with the broadly neutralizing antibody b12 protected humanized mice against repetitive intravaginal infection in a dose-dependent manner. In addition, treatment with the antibody PGT126, which is more potent in vitro, was more efficacious in vivo and provided sterilizing protection. Our results demonstrate that humanized mice can be used as a small-animal model to study the efficacy and mechanism of broadly neutralizing antibody protection against HIV acquisition. PMID- 27357343 TI - Payne et al (J Infect Dis 2016; 213:1743-51). PMID- 27357342 TI - Reply to Gomez Marin. PMID- 27357344 TI - Parathyroid Hormone-Related Protein Protects Osteoblastic Cells From Oxidative Stress by Activation of MKP1 Phosphatase. AB - Oxidative damage is an important contributor to the morphological and functional changes in osteoporotic bone. Aging increases the levels of reactive oxygen species (ROS) that cause oxidative stress and induce osteoblast apoptosis. ROS modify several signaling responses, including mitogen-activated protein kinase (MAPK) activation, related to cell survival. Both parathyroid hormone (PTH) and its bone counterpart, PTH-related protein (PTHrP), can regulate MAPK activation by modulating MAPK phosphatase-1 (MKP1). Thus, we hypothesized that PTHrP might protect osteoblasts from ROS-induced apoptosis by targeting MKP1. In osteoblastic MC3T3-E1 and MG-63 cells, H2 O2 triggered p38, JNK, ERK and p66Shc phosphorylation, and cell apoptosis. Meanwhile, PTHrP (1-37) rapidly but transiently increased ERK and Akt phosphorylation without affecting p38, JNK, or p66Shc activation. H2 O2 -induced p38 and ERK phosphorylation and apoptosis were both decreased by pre-treatment with specific kinase inhibitors or PTHrP (1-37) in both osteoblastic cell types. These dephosphorylating and prosurvival actions of PTHrP (1-37) were prevented by a phosphatase inhibitor cocktail, the phosphatase MKP1 inhibitor sanguinarine or a MKP1 siRNA. PTHrP (1-37) promptly enhanced MKP1 protein and gene expression and MKP1-dependent catalase activity in osteoblastic cells. Furthermore, exposure to PTHrP (1-37) adsorbed in an implanted hydroxyapatite-based ceramic into a tibial defect in aging rats increased MKP1 and catalase gene expression in the healing bone area. Our findings demonstrate that PTHrP counteracts the pro-apoptotic actions of ROS by a mechanism dependent on MKP1-induced dephosphorylation of MAPKs in osteoblasts. J. Cell. Physiol. 232: 785-796, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27357345 TI - Impact of amorphization on the electronic properties of Zn-Ir-O systems. AB - We analyze the geometry and electronic structure of a series of amorphous Zn-Ir-O systems using classical molecular dynamics followed by density functional theory taking into account two different charge states of Ir (+3 and +4). The structures obtained consist of a matrix of interconnected metal-oxygen polyhedra, with Zn adopting preferentially a coordination of 4 and Ir a mixture of coordinations between 4 and 6 that depend on the charge state of Ir and its concentration. The amorphous phases display reduced band gaps compared to crystalline ZnIr2O4 and exhibit localized states near the band edges, which harm their transparency and hole mobility. Increasing amounts of Ir in the Ir(4+) phases decrease the band gap further while not altering it significantly in the Ir(3+) phases. The results are consistent with recent transmittance and resistivity measurements. PMID- 27357346 TI - Tunnelling current-voltage characteristics of Angstrom gaps measured with terahertz time-domain spectroscopy. AB - Quantum tunnelling becomes inevitable as gap dimensions in metal structures approach the atomic length scale, and light passing through these gaps can be used to examine the quantum processes at optical frequencies. Here, we report on the measurement of the tunnelling current through a 3-A-wide metal-graphene-metal gap using terahertz time-domain spectroscopy. By analysing the waveforms of the incident and transmitted terahertz pulses, we obtain the tunnelling resistivity and the time evolution of the induced current and electric fields in the gap and show that the ratio of the applied voltage to the tunnelling current is constant, i.e., the gap shows ohmic behaviour for the strength of the incident electric field up to 30 kV/cm. We further show that our method can be extended and applied to different types of nanogap tunnel junctions using suitable equivalent RLC circuits for the corresponding structures by taking an array of ring-shaped nanoslots as an example. PMID- 27357348 TI - Zika virus-associated neurological disorders: a review. AB - Zika virus, an arbovirus transmitted by mosquitoes of the Aedes species, is now rapidly disseminating throughout the Americas and the ongoing Brazilian outbreak is the largest Zika virus epidemic so far described. In addition to being associated with a non-specific acute febrile illness, a number of neurological manifestations, mainly microcephaly and Guillain-Barre syndrome, have been associated with infection. These with other rarer neurological conditions suggest that Zika virus, similar to other flaviviruses, is neuropathogenic. The surge of Zika virus-related microcephaly cases in Brazil has received much attention and the role of the virus in this and in other neurological manifestations is growing. Zika virus has been shown to be transmitted perinatally and the virus can be detected in amniotic fluid, placenta and foetus brain tissue. A significant increase in Guillain-Barre syndrome incidence has also been reported during this, as well as in previous outbreaks. More recently, meningoencephalitis and myelitis have also been reported following Zika virus infection. In summary, while preliminary studies have suggested a clear relationship between Zika virus infection and certain neurological conditions, only longitudinal studies in this epidemic, as well as experimental studies either in animal models or in vitro, will help to better understand the role of the virus and the pathogenesis of these disorders. PMID- 27357347 TI - 18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers. AB - Tau positron emission tomography ligands provide the novel possibility to image tau pathology in vivo However, little is known about how in vivo brain uptake of tau positron emission tomography ligands relates to tau aggregates observed post mortem. We performed tau positron emission tomography imaging with (18)F-AV-1451 in three patients harbouring a p.R406W mutation in the MAPT gene, encoding tau. This mutation results in 3- and 4-repeat tau aggregates similar to those in Alzheimer's disease, and many of the mutation carriers initially suffer from memory impairment and temporal lobe atrophy. Two patients with short disease duration and isolated memory impairment exhibited (18)F-AV-1451 uptake mainly in the hippocampus and adjacent temporal lobe regions, correlating with glucose hypometabolism in corresponding regions. One patient died after 26 years of disease duration with dementia and behavioural deficits. Pre-mortem, there was (18)F-AV-1451 uptake in the temporal and frontal lobes, as well as in the basal ganglia, which strongly correlated with the regional extent and amount of tau pathology in post-mortem brain sections. Amyloid-beta ((18)F-flutemetamol) positron emission tomography scans were negative in all cases, as were stainings of brain sections for amyloid. This provides strong evidence that (18)F-AV-1451 positron emission tomography can be used to accurately quantify in vivo the regional distribution of hyperphosphorylated tau protein. PMID- 27357350 TI - The superficial white matter in temporal lobe epilepsy: a key link between structural and functional network disruptions. AB - Drug-resistant temporal lobe epilepsy is increasingly recognized as a system level disorder affecting the structure and function of large-scale grey matter networks. While diffusion magnetic resonance imaging studies have demonstrated deep fibre tract alterations, the superficial white matter immediately below the cortex has so far been neglected despite its proximity to neocortical regions and key role in maintaining cortico-cortical connectivity. Using multi-modal 3 T magnetic resonance imaging, we mapped the topography of superficial white matter diffusion alterations in 61 consecutive temporal lobe epilepsy patients relative to 38 healthy controls and studied the relationship to large-scale structural as well as functional networks. Our approach continuously sampled mean diffusivity and fractional anisotropy along surfaces running 2 mm below the cortex. Multivariate statistics mapped superficial white matter diffusion anomalies in patients relative to controls, while correlation and mediation analyses evaluated their relationship to structural (cortical thickness, mesiotemporal volumetry) and functional parameters (resting state functional magnetic resonance imaging amplitude) and clinical variables. Patients presented with overlapping anomalies in mean diffusivity and anisotropy, particularly in ipsilateral temporo-limbic regions. Diffusion anomalies did not relate to cortical thinning; conversely, they mediated large-scale functional amplitude decreases in patients relative to controls in default mode hub regions (i.e. anterior and posterior midline regions, lateral temporo-parietal cortices), and were themselves mediated by hippocampal atrophy. With respect to clinical variables, we observed more marked diffusion anomalies in patients with a history of febrile convulsions and those with longer disease duration. Similarly, more marked diffusion alterations were associated with seizure-free outcome. Bootstrap analyses indicated high reproducibility of our findings, suggesting generalizability. The temporo-limbic distribution of superficial white matter anomalies, together with the mediation level findings, suggests that this so far neglected region serves a key link between the hippocampal atrophy and large-scale default mode network alterations in temporal lobe epilepsy. PMID- 27357349 TI - Atrophy, hypometabolism and clinical trajectories in patients with amyloid negative Alzheimer's disease. AB - See O'Sullivan and Vann (doi:10.1093/aww166) for a scientific commentary on this article.About 15% of patients clinically diagnosed with Alzheimer's disease do not show high tracer retention on amyloid positon emission tomography imaging. The present study investigates clinical and demographic features, patterns of brain atrophy and hypometabolism and longitudinal clinical trajectories of these patients. Forty amyloid-negative patients carrying a pre-scan diagnosis of Alzheimer's disease dementia from four centres were included (11/29 females/males; mean age = 67 +/- 9). Detailed clinical histories, including the clinical diagnoses before and after the amyloid scan and at follow-up, were collected. Patients were classified according to their pre-scan clinical phenotype as amnestic (memory predominant), non-amnestic (predominant language, visuospatial or frontal symptoms), or non-specific (diffuse cognitive deficits). Demographic, clinical, neuropsychological, magnetic resonance imaging and (18)F fluorodeoxyglucose positon emission tomography data were compared to 27 amyloid positive typical Alzheimer's disease cases (14/13 females/males; mean age = 71 +/ 10) and 29 amyloid-negative controls (15/14 females/males; mean age = 69 +/- 12) matched for age, gender and education. There were 21 amnestic, 12 non-amnestic, and seven non-specific amyloid-negative Alzheimer's disease cases. Amyloid negative subgroups did not differ in age, gender or education. After the amyloid scan, clinicians altered the diagnosis in 68% of amyloid-negative patients including 48% of amnestic versus 94% of non-amnestic and non-specific cases. Amnestic amyloid-negative cases were most often reclassified as frontotemporal dementia, non-amnestic as frontotemporal dementia or corticobasal degeneration, and non-specific as dementia with Lewy bodies or unknown diagnosis. The longer term clinical follow-up was consistent with the post-scan diagnosis in most cases (90%), including in amnestic amyloid-negative cases whose post-positon emission tomography diagnosis remained Alzheimer's disease. While the non-amnestic and non specific amyloid-negative cases usually showed patterns of atrophy and hypometabolism suggestive of another degenerative disorder, the amnestic amyloid negative cases had subtle atrophy and hypometabolism, restricted to the retrosplenial/posterior cingulate cortex. Patients with a negative amyloid positon emission tomography scan following an initial clinical diagnosis of Alzheimer's disease have heterogeneous clinical presentations and neuroimaging profiles; a majority showed a clinical progression that was consistent with a neurodegenerative condition. In contrast, in the subgroup of amnestic amyloid negative cases, the clinical presentation and follow-up usually remained consistent with Alzheimer's disease. An alternative diagnosis was not made in about half of the amnestic amyloid-negative cases, highlighting the need for a clinical framework and terminology to define these patients, who may have underlying limbic-predominant, non-amyloid-related pathologies. PMID- 27357351 TI - [Characterization of the seriously injured cyclist : An evaluation of the injury and treatment focus areas of 2817 patients]. AB - BACKGROUND: Transport statistics classify bicyclists in a separate road user collective. For medical reasons, this differentiation is applied as well. Much literature is published in this field. Nevertheless there is a lack of literature regarding the overall injury patterns in a defined injury severity collective. Most literature is about isolated injured regions in combination with a heterogeneous injury severity. Further parameters, such as injury patterns, epidemiological aspects, treatment focal points and characteristic outcomes, have also been studied. The aim of the present study was to evaluate and characterize injury patterns in a standardized and representative collective of severely injured bicyclists. Methods We analysed data from the Traumaregister DGU(r) from 2002 to 2010. In total, 2817 severely injured (ISS >= 9 and additional intensive/intermediate care unit) bicyclists were included. The primary endpoint was evaluation of injury patterns and injury focal points. In addition to that we analysed parameters like epidemiological aspects, circumstances of accident, treatment focal points and outcome. RESULTS: The mean age was 50.3 +/- 20.9 years. Males accounted for 68.9 % (n = 1940). The mean ISS was 23.7 +/- 12.6. The mean AIS regions were the head 71.9 % (n = 2025), the chest with 44.9 % (n = 1264) and the upper extremities 33.6 % (947). In 68.2 % of all cases an ISS >= 9 was achieved by a traumatic brain injury; 21.1 % of all cases were mono-injuries. A characteristic distribution of age and a characteristic prevalence of the accidents in relation to the weekday and the month could be shown. CONCLUSION: The present study analysed the largest ever published collective of severely injured bicyclists. Traumatic brain injury could clearly be shown as the main injury in this collective. Moreover, one of five cases achieved the state "severely injured" due to mono-injury. PMID- 27357352 TI - [Parameters influencing the preclinical application of cervical collars]. AB - BACKGROUND: The application of cervical collars is a standard procedure in emergency care of trauma patients. It is often observed that the application of cervical collars is performed incorrectly, which may lead to reduced immobilization of the cervical spine. OBJECTIVES: The objective of this study was to analyze the practical skills of professional emergency care providers concerning the application of cervical collars. MATERIALS AND METHODS: Emergency care professionals (n = 104) were asked to apply a cervical collar to a training doll. Each performance step was assessed separately. Furthermore, personal and occupational data of all study participants were collected using a questionnaire. RESULTS: The study participants included professional rescue personnel and emergency physicians. The average occupational experience of all study participants in out-of-hospital emergency care was 11.1 +/- 8.9 years. Most participants had already received training on trauma care (61 %) and felt "very confident" in handling a cervical collar (84 %). The application of the cervical collar was performed correctly in 11 % of the performances. The most common error was incorrect size adjustment of the cervical collar (66 %). No association was found between the correct application of the cervical collar and possible parameters of influence, such as working experience in emergency care or participation in trauma courses. CONCLUSIONS: Despite pronounced subjective confidence regarding the application of cervical collars, this study shows that there are general deficits in the practical skills of applying cervical collars. Therefore, a critical assessment of the current training contents on the subject of trauma care must be demanded. PMID- 27357353 TI - CHARACTERIZATION OF NICOTINE ACETYLCHOLINE RECEPTOR SUBUNITS IN THE COCKROACH Periplaneta americana MUSHROOM BODIES REVEALS A STRONG EXPRESSION OF beta1 SUBUNIT: INVOLVEMENT IN NICOTINE-INDUCED CURRENTS. AB - Nicotinic acetylcholine receptors are ligand-gated ion channels expressed in many insect structures, such as mushroom bodies, in which they play a central role. We have recently demonstrated using electrophysiological recordings that different native nicotinic receptors are expressed in cockroach mushroom bodies Kenyon cells. In the present study, we demonstrated that eight genes coding for cockroach nicotinic acetylcholine receptor subunits are expressed in the mushroom bodies. Quantitative real-time polymerase chain reaction (PCR) experiments demonstrated that beta1 subunit was the most expressed in the mushroom bodies. Moreover, antisense oligonucleotides performed against beta1 subunit revealed that inhibition of beta1 expression strongly decreases nicotine-induced currents amplitudes. Moreover, co-application with 0.5 MUM alpha-bungarotoxin completely inhibited nicotine currents whereas 10 MUM d-tubocurarine had a partial effect demonstrating that beta1-containing neuronal nicotinic acetylcholine receptor subtypes could be sensitive to the nicotinic acetylcholine receptor antagonist alpha-bungarotoxin. PMID- 27357354 TI - Clinical characterization and outcome of primary bone lymphoma: a retrospective study of 61 Chinese patients. AB - Primary bone lymphoma(PBL) is a rare disease. To assess the clinical characteristics, outcome, and prognostic factors of this entity in Chinese population, we retrospectively analyzed 61 PBL patients initially treated in our institution between 1997 and 2014. The median age was 45 years. The most common histological subtype was diffuse large B-cell lymphoma (DLBCL) (55.7%), followed by T-cell lymphoma (18.0%). All patients underwent systemic chemotherapy as initial treatment while 24 patients (39.3%) were additionally treated with radiotherapy. The 5-year overall survival (OS) and the 5-year progression-free survival (PFS) rates of 57 cases with completed follow-up were 52.3% and 40.1%, respectively. In further analysis of the primary bone DLBCL (PB-DLBCL) subgroup, the 5-year OS and PFS rates were 53.0% and 47.0%, and a multivariable analysis revealed that baseline Eastern Cooperative Oncology Group (ECOG) score and response to initial treatment (complete remission versus no complete remission) were independent prognostic factors for both OS and PFS. The proportion of T-cell lymphoma is higher in China than in western populations. High baseline ECOG scores (>=2) and unachieved CR in initial therapy were factors for poor PB-DLBCL prognosis. The role of radiotherapy and rituximab in PLB therapy remains to be confirmed in further investigation. PMID- 27357355 TI - Circulating microRNAs strongly predict cardiovascular death in patients with coronary artery disease-results from the large AtheroGene study. AB - Introduction: Stratification for subsequent coronary events among patients with coronary artery disease (CAD) is of considerable interest because of the potential to guide secondary preventive therapies. Recently, we identified eight microRNAs (miRNAs), which facilitated acute coronary syndrome (ACS) diagnosis. In this study, we aimed to evaluate their potential role as prognostic biomarkers for cardiovascular disease. Methods: The serum concentrations of eight candidate miRNAs -miR-19a, miR-19b, miR-132, miR-140-3p, miR-142-5p, miR-150, miR-186, and miR-210 were measured in a cohort of 1112 patients with documented CAD-including 430 patients with ACS and 682 patients with stable angina pectoris. Cardiovascular death was the main outcome measure. Results: During a median follow-up of 4.0 years, most miRNAs reliably predicted cardiovascular death in ACS patients. Cox regression analyses indicated that in particular miR-132 (HR 2.85 per 1 SD increase, P = 0.022), miR-140-3p (HR 2.88 per 1 SD increase, P = 0.022), and miR-210 (HR 3.10 per 1 SD increase, P = 0.039) were able to precisely predict cardiovascular death. Circulating miR-132, miR-140-3p, and miR-210 clearly improved various model performance measures, including C-statistics (AUC [area under the receiver-operating characteristic curve] for miR-132: 0.737; AUC for miR-140-3p: 0.756; AUC for miR-210: 0.754). Conclusions: This is the largest study so far evaluating the prognostic value of circulating miRNAs in cardiovascular disease. Our study shows that single miRNAs derived from peripheral blood predict mortality in secondary prevention settings, and thereby represent valuable biomarkers for risk estimation in CAD. PMID- 27357356 TI - Increased haematopoietic activity in patients with atherosclerosis. AB - Aims: Experimental work posits that acute ischaemic events trigger haematopoietic activity, driving monocytosis, and atherogenesis. Considering the chronic low grade inflammatory state in atherosclerosis, we hypothesized that haematopoietic hyperactivity is a persistent feature in cardiovascular disease (CVD). Therefore, we aimed to assess the activity of haematopoietic organs and haematopoietic stem and progenitor cells (HSPCs) in humans. Methods and results: First, we performed 18F-fluorodeoxyglucose positron emission tomographic (18F-FDG PET) imaging in 26 patients with stable atherosclerotic CVD (ischaemic event >12 months ago), and 25 matched controls. In splenic tissue, 18F-FDG uptake was 2.68 +/- 0.65 in CVD patients vs. 1.75 +/- 0.54 in controls (1.6-fold higher; P< 0.001), and in bone marrow 3.20 +/- 0.76 vs. 2.72 +/- 0.46 (1.2-fold higher; P = 0.003), closely related to LDL cholesterol levels (LDLc, r = 0.72). Subsequently, we determined progenitor potential of HSPCs harvested from 18 patients with known atherosclerotic CVD and 30 matched controls; both groups were selected from a cohort of cancer patients undergoing autologous stem cell transplantation. In CVD patients, the normalized progenitor potential, expressed as the number of colony forming units-granulocyte/monocyte (CFU-GM) colonies/CD34+ cell, was 1.6-fold higher compared with matched controls (P < 0.001). Finally, we assessed the effects of native and oxidized lipoproteins on HSPCs harvested from healthy donors in vitro. Haematopoietic stem and progenitor cells displayed a 1.5-fold increased CFU-GM capacity in co-culture with oxidized LDL in vitro (P = 0.002), which was inhibited by blocking oxidized phospholipids via E06 (P = 0.001). Conclusion: Collectively, these findings strengthen the case for a chronically affected haematopoietic system, potentially driving the low-grade inflammatory state in patients with atherosclerosis. PMID- 27357357 TI - Should we reconsider the role of age in treatment allocation for primary prevention of cardiovascular disease? PMID- 27357358 TI - Impact of high-sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction. AB - AIMS: High-sensitivity cardiac troponin (hs-cTn) assays provide higher diagnostic accuracy for acute myocardial infarction (AMI) when compared with conventional assays, but may result in increased use of unnecessary coronary angiographies due to their increased detection of cardiomyocyte injury in conditions other than AMI. METHODS AND RESULTS: We evaluated the impact of the clinical introduction of high-sensitivity cardiac troponin T (hs-cTnT) on the use of coronary angiography, stress testing, and time to discharge in 2544 patients presenting with symptoms suggestive of AMI to the emergency department (ED) within a multicentre study either before (1455 patients) or after (1089 patients) hs-cTnT introduction. Acute myocardial infarction was more often the clinical discharge diagnosis after hs-cTnT introduction (10 vs. 14%, P < 0.001), while unstable angina less often the clinical discharge diagnosis (14 vs. 9%, P = 0.007). The rate of coronary angiography was similar before and after the introduction of hs-cTnT (23 vs. 23%, P = 0.092), as was the percentage of coronary angiographies showing no stenosis (11 vs. 7%, P = 0.361). In contrast, the use of stress testing was substantially reduced from 29 to 19% (P < 0.001). In outpatients, median time to discharge from the ED decreased by 79 min (P < 0.001). Mean total costs decreased by 20% in outpatients after the introduction of hs-cTnT (P = 0.002). CONCLUSION: The clinical introduction of hs-cTn does not lead to an increased or inappropriate use of coronary angiography. Introduction of hs-cTn is associated with an improved rule-out process and thereby reduces the need for stress testing and time to discharge. CLINICAL TRIAL REGISTRATION INFORMATION: www.clinicaltrials.gov. Identifier, NCT00470587. PMID- 27357361 TI - Field driven charging dynamics of a fluidized granular bed. AB - A simplified model has previously described the inductive charging of colliding identical grains in the presence of an external electric field. Here we extend that model by including heterogeneous surface charge distributions, grain rotations and electrostatic interactions between grains. We find from this more realistic model that strong heterogeneities in charging can occur in agitated granular beds, and we predict that shielding due to these heterogeneities can dramatically alter the charging rate in such beds. PMID- 27357359 TI - Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF. AB - AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362. PMID- 27357360 TI - Unfavorable neuroblastoma prognostic factor NLRR2 inhibits cell differentiation by transcriptional induction through JNK pathway. AB - The novel human gene family encoding neuronal leucine rich repeat (NLRR) proteins were identified as prognostic markers from our previous screening of primary neuroblastoma (NB) cDNA libraries. Of the NLRR gene family members, NLRR1 and NLRR3 are associated with the regulation of cellular proliferation and differentiation, respectively. However, the functional regulation and clinical significance of NLRR2 in NB remain unclear. Here, we evaluated the differential expression of NLRR2, where high expressions of NLRR2 were significantly associated with a poor prognosis of NB (P = 0.0009), in 78 NBs. Enforced expression of NLRR2 in NB cells enhanced cellular proliferation and induced resistance to retinoic acid (RA)-mediated cell growth inhibition. In contrast, knockdown of NLRR2 exhibited growth inhibition effects and enhanced RA-induced cell differentiation in NB cells. After RA treatment, NLRR2 expression was increased and correlated with the upregulation of c-Jun, a member of the activator protein-1 (AP-1) family in NB cells. Moreover, the expressions of NLRR2 and c-Jun were suppressed by treatment with a JNK inhibitor, which ameliorated the promoter activity of the NLRR2 gene while knockdown of c-Jun reduced NLRR2 expression. We then searched AP-1 binding consensus in the NLRR2 promoter region and confirmed c-Jun recruitment at a consensus. Conclusively, NLRR2 must be an inducible gene regulated by the JNK pathway to enhance cell survival and inhibit NB cell differentiation. Therefore, NLRR2 should have an important role in NB aggressiveness and be a potential therapeutic target for the treatment of RA resistant and aggressive NB. PMID- 27357362 TI - Streptococcus mutans, Streptococcus sobrinus and Candida albicans in oral samples from caries-free and caries-active children. AB - AIM: This was to examine the occurrence of S. mutans, S. sobrinus and C. albicans in dental plaque and saliva from caries-free and caries-active Greek children. METHODS: Saliva and dental plaque samples from 46 caries-free and 51 caries active 3-to-13-year-old children were examined using selective media for the three microbes. Identification of isolated mutans streptococci (S. mutans and S. sobrinus) was performed with biochemical test and specific DNA probes. The salivary levels of mutans streptococci were additionally determined by a chair side test (Dentocult(r) SM strips). RESULTS: The isolation frequencies of S. mutans, S. sobrinus and C. albicans were 66, 11 and 18 %, respectively. Caries active children harboured more frequently and at significantly higher numbers the specific microbes than caries-free children. A similar pattern was observed with the Dentocult(r) SM strip scores. No correlation was found between the presence of these microbes and the age or gender of the children. CONCLUSIONS: Caries experience was statistically significantly related to the presence of all three microbes under study, both in dental plaque and saliva. PMID- 27357364 TI - Need for symptomatic management in advanced multiple sclerosis. AB - OBJECTIVE: A majority of patients with advanced multiple sclerosis (MS) need symptomatic treatment. Many MS-related symptoms may not be recognized and thus are not treated. We conducted a study to estimate the prevalence of inadequate symptomatic treatment of patients with advanced MS. METHODS: Patients with advanced MS admitted to a specialist MS rehabilitation clinic were included in this study. Severity was assessed using the Expanded Disability Status Scale (EDSS). The information we collected included age of onset, initial course, time to sustained disability, pharmacological treatment, degree of spasticity, pain and bladder dysfunction, and unmet needs of symptomatic treatment. RESULTS: In total, we assessed demographic and clinical characteristics in 129 patients with a mean age of 56 years and a median EDSS of 7.5. The proportion with inadequate symptom treatment was regarding spasticity 46%, pain 28%, and bladder dysfunction 23%. DISCUSSION: This study showed that a large proportion of patients with advanced MS had lack of symptomatic treatment. These patients probably underuse neurological specialist services. Better symptomatic treatment could contribute to improving quality of life of people with MS. PMID- 27357363 TI - Intercomparison of salivary nitric oxide as a biomarker of dental caries risk between caries-active and caries-free children. AB - AIM: To determine the efficacy of salivary nitric oxide as a biomarker for dental caries risk in children and to compare the salivary nitric oxide levels in caries active and caries-free children. METHODS: One hundred children aged 6-12 years were selected and were divided into two groups according to DMFT index: as caries free consisting of 50 individuals (DMFT/dmft = 0) and caries-active group (DMFT/dmft >=3) consisting of 50 individuals. The saliva collected was estimated for nitric oxide level by Griess reaction method. Paired t test was used to correlate the difference of mean salivary nitric oxide levels between caries active and caries-free groups. RESULTS: The mean level of nitric oxide in saliva of the control group was 581.3 +/- 134.6 MUg/mL and that of caries-active group was 335.4 +/- 111.1 MUg/mL, respectively. The mean salivary level of nitric oxide was higher in the caries-free group as compared with the caries-active group which was statistically significant (p = 0.000). CONCLUSIONS: Salivary nitric oxide was higher in the caries-free group as compared to the caries-active group which suggests that increased production of nitric oxide in the oral cavity may contribute to lower caries incidence in children. PMID- 27357365 TI - Bone regeneration following the in vivo bioreactor principle: is in vitro manipulation of exogenous elements still needed? AB - Large bone defect treatment is a key challenge due to the difficulty of functional and aesthetic reconstruction. A promising approach for bone regeneration is bone tissue engineering which is based on in vitro manipulation of seed cells, growth factors and bioscaffolds. However, many formidable conceptual and technical challenges impede clinical translation of experimental successes into clinical practices. An emerging strategy for bone regeneration is using the body as a bioreactor to cultivate the traditional triad and leveraging the body's own regenerative capacity to create new bone tissue. Based on the understanding of bone regeneration and in vivo bioreactor principle, we hypothesize that functional bone tissue may be eventually generated in vivo only using autologous costal periosteum, without participation of any exogenous elements. PMID- 27357366 TI - Effect of dietary threonine on laying performance and intestinal immunity of laying hens fed low-crude-protein diets during the peak production period. AB - Threonine (Thr) may be a limiting amino acid for laying hens fed diets with lowered protein level. An experiment was conducted to examine laying performance, and the intestinal immune function of laying hens provided diets varying in digestible Thr levels. Lohmann Brown laying hens (n = 480), 28 weeks of age, were allocated to six dietary treatments, each of which included five replicates of 16 hens. Dietary crude protein (CP) 16.18% diet was offered as the positive control diet. L-Thr was added to the negative diet (14.16% CP) by 0, 1.0, 2.0, 3.0 and 4.0 g/kg, corresponding 0.44%, 0.43%, 0.49%, 0.57%, 0.66% and 0.74% digestible Thr. At 40 weeks, a reduction in CP level decreased laying performance (p < 0.05). In the low CP, increasing dietary Thr increased (p < 0.05) egg production and egg mass and rose to a plateau between 0.57% and 0.66%. The hens fed 0.66% Thr showed the lowest value (p < 0.05) of feed conversion ratio (FCR). Serum level of uric acid showed the lowest values (p < 0.05) at 0.57-0.66%. In addition, serum-free Thr maximized (p < 0.05) between 0.66% and 0.74%. Digestive trypsin activity decreased (p < 0.05) when hens fed the low-CP diet compared with hens fed CP (16.18%) and hens fed 0.57-0.66%. Expressions of ileal MUC2 mRNA maximized (p < 0.05) at 0.66% Thr. Occludin mRNA increased with increasing Thr level (p < 0.05). sIgA mRNA reached to the maximum level (p < 0.05) at 0.66% and 0.74% Thr. INF-gamma mRNA reached to the lowest level (p < 0.05) at 0.65%. Expressions of ileal IL-2, IL-6, IL-1beta mRNA decreased with increasing Thr level (p < 0.05). In conclusion, Thr supplementation resulting in optimal laying performance and stimulated the mucosal immune system, suggesting that it is a limiting amino acid in the low-crude-protein diet of laying hens during the peak production period. PMID- 27357368 TI - Fifteen-year mortality of patients with asthma-COPD overlap syndrome. AB - BACKGROUND: The coexistence of asthma and chronic obstructive pulmonary disease (asthma-COPD overlap syndrome: ACOS) is increasingly recognized but data about its prevalence and long-term mortality are needed. METHODS: Prevalence of ACOS and 15-year mortality rates were assessed in 1065 subjects aged >65years, enrolled in the SA.R.A. study, with complete clinical, lung functional and follow up data. Physical performance, disease-related disability, and health-related quality of life (HRQL) were also evaluated. RESULTS: ACOS was found in 11.1% of subjects (29.4% of those previously diagnosed with COPD and 19.7% of those with asthma). ACOS was positively associated with impaired physical performance, functional ability, and HRQL. Individuals with ACOS had higher mortality rates than controls (7.17 per 100 person-years; mortality rate ratio: 1.83). After adjustment for the main confounders, the risk of all-cause mortality remained significantly increased in subjects with ACOS (HR: 1.82), COPD (HR: 2.12), and restriction (HR: 2.41), but not asthma. CONCLUSIONS: Long-term prognosis of ACOS was similar to COPD, and worse than asthma and healthy controls. ACOS had a significant impact on physical performance, functional ability, and HRQL. PMID- 27357367 TI - The first characterization of multidrug and toxin extrusion (MATE/SLC47) proteins in zebrafish (Danio rerio). AB - Multidrug and toxin extrusion (MATE) proteins are involved in the extrusion of endogenous compounds and xenobiotics across the plasma membrane. They are conserved from bacteria to mammals, with different numbers of genes within groups. Here, we present the first data on identification and functional characterization of Mate proteins in zebrafish (Danio rerio). Phylogenetic analysis revealed six Mates in teleost fish, annotated as Mate3-8, which form a distinct cluster separated from the tetrapod MATEs/Mates. Synteny analysis showed that zebrafish mate genes are orthologous to human MATEs. Gene expression analysis revealed that all the mate transcripts were constitutively and differentially expressed during embryonic development, followed by pronounced and tissue-specific expression in adults. Functional analyses were performed using transport activity assays with model substrates after heterologous overexpression of five zebrafish Mates in HEK293T cells. The results showed that zebrafish Mates interact with both physiological and xenobiotic substances but also substantially differ with respect to the interacting compounds and interaction strength in comparison to mammalian MATEs/Mates. Taken together, our data clearly indicate a potentially important role for zebrafish Mate transporters in zebrafish embryos and adults and provide a basis for detailed functional characterizations of single zebrafish Mate transporters. PMID- 27357370 TI - Use of archival data on Indian residential schools. PMID- 27357369 TI - Anthropometric indices of First Nations children and youth on first entry to Manitoba/Saskatchewan residential schools-1919 to 1953. AB - BACKGROUND: First Nations people are experiencing increasing rates of obesity and type 2 diabetes but no anthropometric information exists from before the 1950s to provide context to these epidemics. OBJECTIVE: To compare anthropometric indices of First Nations children and youth on first entering residential schools with historical and contemporary reference groups. METHODS: This observational cross sectional study used archival records from the Department of Indian Affairs to calculate body mass index (BMI), height for age (HA) and weight for age (WA) of all known children and youth undergoing physical examinations on first entering residential schools in Saskatchewan and Manitoba from 1919 to 1953. Proportions of children and youth in each BMI category were determined by age, sex, time period and residential school. Z-scores for HA and WA were determined by age group and sex. Finally, median heights and weights were compared with a non Indigenous cohort from the 1953 Canadian survey. RESULTS: On admission to residential schools, 1,767 First Nations children and youth (847 boys, 920 girls) were more likely to have normal BMIs (79.8%) than Canadian children and youth today (66.5%), but lower rates of overweight/obesity (10.9% vs. 32.0%) and higher rates of underweight (9.3% vs. <2.0%). There was an overall trend of diminishing levels of underweight and increasing levels of overweight/obesity over time. Although 6.6% of boys and 7.9% of girls had HA Z-scores >-2, age-specific median heights tended to be higher than Canadian children and youth in 1953. Under 3% of children and youth had WA Z-scores of >-2. CONCLUSIONS: A large majority of First Nations children and youth exhibited normal anthropometric indices on first entering residential schools in Manitoba and Saskatchewan from 1919 to 1953. These historical findings provide an important context to the current epidemics of obesity and type 2 diabetes and suggest that the nutritional conditions in these First Nations children's communities were satisfactory during the residential school era. PMID- 27357371 TI - Reflections on ethical challenges encountered in Indigenous health research using archival records. PMID- 27357372 TI - Indigenous people should decide on matters of access to archival information. PMID- 27357374 TI - Midgut fungal and bacterial microbiota of Aedes triseriatus and Aedes japonicus shift in response to La Crosse virus infection. AB - Understanding how midgut microbial communities of field-collected mosquitoes interact with pathogens is critical for controlling vector infection and disease. We used 16S rRNA and internal transcribed spacer sequencing to characterize the midgut bacterial and fungal communities of adult females of Aedes triseriatus and Aedes japonicus collected as pupae in tree holes, plastic bins and waste tires and their response to La Crosse virus (LACV) infection. For both mosquito species and across all habitat and virus treatments, a total of 62 bacterial operational taxonomic units (OTUs) from six phyla and 21 fungal OTUs from two phyla were identified. The majority of bacterial (92%) and fungal (71%) OTUs were shared between the mosquito species; however, several OTUs were unique to each species. Bacterial and fungal communities of individuals that took either infectious or noninfectious bloodmeals were less diverse and more homogeneous compared to those of newly emerged adults. Interestingly, LACV-infected A. triseriatus and A. japonicus had higher bacterial richness and lower fungal richness compared to individuals that took a noninfectious bloodmeal, suggesting that viral infection was associated with an increase in bacterial OTUs and a decrease in fungal OTUs. For both mosquito species, several OTUs were identified that had both high fidelity and specificity to mosquito midguts that were infected with LACV. Overall, these findings demonstrate that bacterial and fungal communities that reside in mosquito midguts respond to host diet and viral infection and could play a role in modulating vector susceptibility to LACV. PMID- 27357375 TI - Probing the Surface Properties of Gold at Low Electrolyte Concentration. AB - Using the surface force balance (SFB), we studied the surface properties of gold in aqueous solution with low electrolyte concentration (~10(-5) M and pH = 5.8), i.e., water with no added salt, by directly measuring the interaction between an ultrasmooth gold surface (ca. 0.2 nm rms roughness) and a mica surface. Under these conditions, specific adsorption of ions is minimized and its influence on the surface charge and surface potential of gold is markedly reduced. At open circuit potential, the electrostatic interaction between gold and mica was purely attractive and gold was found to be positively charged. This was further confirmed by force measurements against a positively charged surface, poly-l lysine coated mica. Successive force measurements unambiguously showed that once gold and mica reach contact all counterions are expelled from the gap, confirming that at contact the surface charge of gold is equal and opposite in charge to that of mica. Further analysis of adhesion energy between the surfaces indicated that adhesion is mostly governed by vdW dispersion force and to a lesser extent by electrostatic interaction. Force measurements under external applied potentials showed that the gold-mica interaction can be regulated as a function of applied potential even at low electrolyte concentration. The gold-mica interaction was described very precisely by the nonlinearized Poisson-Boltzmann (PB) equation, where one of the surfaces is at constant charge, i.e., mica, and the other, i.e., gold, is at constant potential. Consequently, the gold surface potential could be determined accurately both at open circuit potential (OCP) and under different applied potentials. Using the obtained surface potentials, we were able to derive fundamental characteristics of the gold surface, e.g., its surface charge density and potential of zero charge (PZC), at very low electrolyte concentration. PMID- 27357373 TI - Loss of cortactin causes endothelial barrier dysfunction via disturbed adrenomedullin secretion and actomyosin contractility. AB - Changes in vascular permeability occur during inflammation and the actin cytoskeleton plays a crucial role in regulating endothelial cell contacts and permeability. We demonstrated recently that the actin-binding protein cortactin regulates vascular permeability via Rap1. However, it is unknown if the actin cytoskeleton contributes to increased vascular permeability without cortactin. As we consistently observed more actin fibres in cortactin-depleted endothelial cells, we hypothesised that cortactin depletion results in increased stress fibre contractility and endothelial barrier destabilisation. Analysing the contractile machinery, we found increased ROCK1 protein levels in cortactin-depleted endothelium. Concomitantly, myosin light chain phosphorylation was increased while cofilin, mDia and ERM were unaffected. Secretion of the barrier-stabilising hormone adrenomedullin, which activates Rap1 and counteracts actomyosin contractility, was reduced in plasma from cortactin-deficient mice and in supernatants of cortactin-depleted endothelium. Importantly, adrenomedullin administration and ROCK1 inhibition reduced actomyosin contractility and rescued the effect on permeability provoked by cortactin deficiency in vitro and in vivo. Our data suggest a new role for cortactin in controlling actomyosin contractility with consequences for endothelial barrier integrity. PMID- 27357376 TI - Distribution of Serum Uric Acid in Black Africans and Its Association With Cardiovascular Risk Factors. AB - Hyperuricemia is associated with cardiovascular disease and its prevalence is unknown in black Africans. This study reports hyperuricemia distribution and its association with cardiovascular risk factors in a selected Angolan population. A cross-sectional study in 585 black Africans was performed. Hyperuricemia was defined as uric acid >7.0 mg/dL in men or >5.7 mg/dL in women. Overall prevalence was 25%. Hyperuricemia was associated with hypertension (odds ratio [OR], 2.20; confidence interval [CI], 95% 1.41-3.47), high waist circumference (OR, 1.67; CI, 95% 1.05-2.65), and metabolic syndrome (OR, 1.66; CI, 95% 1.07-2.57). Compared to those with uric acid levels in the first quartile, individuals in the fourth quartile showed higher body mass index, waist circumference, systolic blood pressure, and plasma levels of creatinine and triglycerides. Hypertension, high waist circumference, and metabolic syndrome were the major cardiovascular risk factors associated with hyperuricemia. PMID- 27357377 TI - The survival and characteristics of older people with and without dementia who are hospitalised following intentional self-harm. AB - OBJECTIVE: Characteristics of older people with and without dementia who are hospitalised following self-harm remains largely unexplored. This research compares the characteristics of older people with and without dementia who self harm, compares associations of mental health-related diagnoses with those hospitalised for a self-harm and a non-self-harm injury and examines mortality by injury intent. METHOD: A population-based study of individuals aged 50+ years with and without dementia admitted to hospital for a self-harm injury (and those with other injuries) using linked hospital admission and mortality records during 2003-2012 in New South Wales (NSW), Australia. Health outcomes, including hospital length of stay (LOS), 28-day readmission and 30-day and 12-month mortality were examined by dementia status. RESULTS: There were 427 hospitalisations of individuals with dementia and 11,684 hospitalisations of individuals without dementia following self-harm. The hospitalisation rate for self-harm for individuals with dementia aged 60+ years was double the rate for individuals without dementia (72.2 and 37.5 per 100,000). For both older people with and without dementia, those who self-harmed were more likely to have co existent mental health and alcohol use disorders than individuals who had a non self-harm injury. Individuals with dementia had higher 12-month mortality rates, 28-day readmission and longer LOS than individuals without dementia. CONCLUSION: Dementia is associated with an increased risk of hospitalisation for self-harm in older people and worse outcomes. The high rate of coexistent mental health conditions suggests that interventions which reduce behavioural and psychological symptoms of dementia might reduce self-harm in people with dementia. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27357378 TI - Neuropsychological Effects of Cerebral Amyloid Angiopathy. AB - Cerebral amyloid angiopathy is a condition of the cerebral arterioles and to a lesser extent capillaries and veins, wherein beta-amyloid is deposited. In arterioles, this preferentially targets vascular smooth muscle cells and in the later stages undermines the stability of the vessel. This condition is frequently comorbid with Alzheimer's disease and its role in cognitive impairment and dementia is a topic of considerable recent research. This article reviews recent literature which confirms that CAA independently contributes to cognitive impairment by potentiating the neurodegeneration of Alzheimer's disease, by predisposing to microhemorrhagic and microischemic injury to the brain parenchyma, and by interfering with the autoregulation of CNS blood flow. In this review, we discuss the clinical presentation of cerebral amyloid angiopathy, with a focus on the neuropsychological manifestations of this vasculopathy. PMID- 27357379 TI - CUREs in biochemistry-where we are and where we should go. AB - Integration of research experience into classroom is an important and vital experience for all undergraduates. These course-based undergraduate research experiences (CUREs) have grown from independent instructor lead projects to large consortium driven experiences. The impact and importance of CUREs on students at all levels in biochemistry was the focus of a National Science Foundation funded think tank. The state of biochemistry CUREs and suggestions for moving biochemistry forward as well as a practical guide (supplementary material) are reported here. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):7-12, 2017. PMID- 27357380 TI - High-performance liquid chromatography separation of phthalate acid esters with a MIL-53(Al)-packed column. AB - In this study, a MIL-53(Al)-packed column was successfully prepared and firstly applied to separate phthalate acid esters (butyl benzyl phthalate, di-n-butyl phthalate, diethyl phthalate, bis(2-ethylhexyl) phthalate, and dimethyl phthalate). Their baseline separation could be achieved within 12 min with a mobile phase of methanol/H2 O ratio at 92:8, and the temperature and flow rate was 40 degrees C and 0.6 mL/min, respectively. The stacking effect and electrostatic force were the key factors in the separation. Moreover, there was a substantial linear relation between the peak height, peak area, and the analyte mass, and the relative standard deviations of retention time, peak height, peak area, and half peak width for five replicate separations of the analytes were within the ranges 0.31-0.88%, 0.72-1.52%, 1.33-1.53%, and 0.46-0.95%, respectively. The results of the calculation of the thermodynamics parameters showed that the separation of phthalate acid esters was controlled by both enthalpy change (DeltaH) and entropy change (DeltaS). PMID- 27357381 TI - Executive Functions as Predictors of School Performance and Social Relationships: Primary and Secondary School Students - ERRATUM. PMID- 27357382 TI - Characterization of differential antibody production against hepatitis C virus in different HCV infection status. AB - BACKGROUND: The Centers for Disease Control and Prevention (CDC) issued an update on hepatitis C virus (HCV) testing approach, in which it omitted the use of recombinant immunoblot assay (RIBA) in the diagnostic algorithm and recommended that future studies are needed to evaluate the performance of HCV testing without RIBA. As Egypt has the highest prevalence of HCV worldwide, we aimed to evaluate the value of RIBA in HCV testing in a high prevalence population. Our objective was to clarify whether enzyme linked immunosorbent assay (ELISA) anti-HCV signal to-cutoff (S/CO) ratios were able to discriminate true positive from false positive anti-HCV antibody status and to evaluate the role of RIBA in solving this problem which may lead to a redefined strategy for diagnosis of HCV infection. Our second objective was to elucidate the effects of different HCV peptides of both structural and non-structural proteins on the humoral immune response to HCV infection. METHODS: The current study drew results from 167 individuals divided into three groups: Group I: included 77 HCV antibody positive (ELISA) high risk health care workers (HCW), Group II: included 56 presumably uninfected individuals who showed normal liver enzymes, negative HCV RNA and were asymptomatic. Their ELISA HCV antibody S/C ratio ranged from 0.9 to <5. Group III: included 34 patients enrolled from outpatient clinics of Ain Shams Hospital with persistent viral replication, elevated liver enzymes, and chronic HCV related liver disease. All study participants were assessed for the presence of anti-HCV antibodies by 3(rd) generation ELISA which was confirmed by RIBA. RESULTS: Interpreting the results of both ELISA and RIBA together, false positive results were highly significantly increased in HCW when compared with the other two groups. Indeterminate and false negative results were only found in the presumably uninfected group. For differentiated antibody responses by RIBA, chronic HCV cases had the highest frequency of positive antibody response to core peptides while the presumably uninfected group had the lowest. Antibody response to E2 was found less frequently in chronic cases than Core 1, Core 2 and NS3. The specific antibody response to the different HCV peptides showed the same distribution of frequencies in both chronic HCV cases and the presumably uninfected individuals with the chronic cases having the highest frequencies. This distribution was different from the HCW. The most evident difference was the reaction towards NS3 which was the highest antibody producing peptide in chronic HCV and presumably uninfected individuals whereas in HCW Core1 was the highest. CONCLUSION: The HCV antibody immunoblot assay (RIBA) is still necessary for the detection of false positive cases which can occur quite frequently in countries of high prevalence as Egypt. Indeterminate RIBA results indicate a waning antibody response in elderly individuals who recovered from previous or distant HCV infection. PMID- 27357383 TI - Knotless anchors with sutures external to the anchor body may be at risk for suture cutting through osteopenic bone. AB - OBJECTIVES: This study evaluated the mechanical performance, under low-load cyclic loading, of two different knotless suture anchor designs: sutures completely internal to the anchor body (SpeedScrew) and sutures external to the anchor body and adjacent to bone (MultiFIX P). METHODS: Using standard suture loops pulled in-line with the rotator cuff (approximately 60 degrees ), anchors were tested in cadaveric bone and foam blocks representing normal to osteopenic bone. Mechanical testing included preloading to 10 N and cyclic loading for 500 cycles from 10 N to 60 N at 60 mm/min. The parameters evaluated were initial displacement, cyclic displacement and number of cycles and load at 3 mm displacement relative to preload. Video recording throughout testing documented the predominant source of suture displacement and the distance of 'suture cutting through bone'. RESULTS: In cadaveric bone and foam blocks, MultiFIX P anchors had significantly greater initial displacement, and lower number of cycles and lower load at 3 mm displacement than SpeedScrew anchors. Video analysis revealed 'suture cutting through bone' as the predominant source of suture displacement in cadaveric bone (qualitative) and greater 'suture cutting through bone' comparing MultiFIX P with SpeedScrew anchors in foam blocks (quantitative). The greater suture displacement in MultiFIX P anchors was predominantly from suture cutting through bone, which was enhanced in an osteopenic bone model. CONCLUSIONS: Anchors with sutures external to the anchor body are at risk for suture cutting through bone since the suture eyelet is at the distal tip of the implant and the suture directly abrades against the bone edge during cyclic loading. Suture cutting through bone may be a significant source of fixation failure, particularly in osteopenic bone.Cite this article: Y. Ono, J. M. Woodmass, A. A. Nelson, R. S. Boorman, G. M. Thornton, I. K. Y. Lo. Knotless anchors with sutures external to the anchor body may be at risk for suture cutting through osteopenic bone. Bone Joint Res 2016;5:269-275. DOI: 10.1302/2046-3758.56.2000535. PMID- 27357384 TI - Circulating exosome levels in the diagnosis of steroid-induced osteonecrosis of the femoral head. AB - OBJECTIVES: Circulating exosomes represent novel biomarkers for multiple diseases. In this study, we investigated whether circulating exosome levels could be used as a diagnostic biomarker for steroid-induced osteonecrosis of the femoral head (ONFH). METHODS: We assessed the serum exosome level of 85 patients with steroid-induced ONFH and 115 healthy donors by Nanosight detection. We then assessed the diagnostic accuracy of serum exosomes by receiver operating characteristic curve analysis. RESULTS: The circulating exosome level of the ONFH group was significantly lower than that of control group. The area under the curve was 0.72, suggesting that the level of serum exosomes has moderate diagnostic accuracy for steroid-induced ONFH. CONCLUSION: Circulating exosome levels are valuable in the diagnosis of steroid-induced ONFH.Cite this article: H Y. Zhu, Y-C. Gao, Y. Wang, C-Q. Zhang. Circulating exosome levels in the diagnosis of steroid-induced osteonecrosis of the femoral head. Bone Joint Res 2016;5:276-279. DOI: 10.1302/2046-3758.56.BJR-2015-0014.R1. PMID- 27357385 TI - The invisible work of distributed medical education: exploring the contributions of audiovisual professionals, administrative professionals and faculty teachers. AB - Distributed medical education (DME) is becoming increasingly prevalent. Much of the published literature on DME has focused on the experiences of learners in distributed programs; however, our empirical work leads us to believe that DME changes the context significantly, not only for learners, but also for other important members of the educational community including audiovisual professionals, administrative professionals and faculty teachers. Based on a three-year ethnographic study, we provide a detailed account of how alliances between various workers involved in DME develop to produce and deliver an undergraduate medical curriculum across geographically separate campuses. We explore the question 'What is the work involved in the delivery of a DME program?' and cast a critical gaze on the essential but invisible, and therefore potentially unrecognized and underappreciated, contributions of AV professionals, administrative professionals, and faculty teachers. Our goal is to make visible the complexity of DME, including the essential contributions of these workers. The study was theoretically framed in sociomateriality and conceptually framed in Star and Strauss' notion of articulation work. PMID- 27357386 TI - London Trauma Conference 2015 : London, UK, 8-11 December 2015. PMID- 27357387 TI - Somali Families' Experiences of Parenting in the United States. AB - The purpose of this study was to gain an understanding of first-generation Somali families' experiences of parenting in the United States to discover potential barriers to effective parenting with the goal to design supportive interventions. Using descriptive phenomenological design, 20 Somali families in Seattle, Washington, were interviewed. Interview transcripts were then analyzed using steps outlined by Colaizzi. The overarching theme that emerged was "Parenting: A Balancing Act," which represents Somali parents trying to balance traditional cultural values and parenting traditions with dominant cultural expectations. Participants expressed fear of losing their children to American lifestyle choices, such as drugs or gangs, and misuse of the American system to turn on their parents. Parents also acknowledged the benefits of access to education and health care for children. To cope with the stressors of their new life, participants sought to preserve traditional cultural and religious values, thus strengthening their Somali community. PMID- 27357388 TI - Comparative innocuity and efficacy of live and inactivated sheeppox vaccines. AB - BACKGROUND: Sheeppox (SPP) is one of the priorities, high-impact animal diseases in many developing countries, where live attenuated vaccines are routinely used against sheeppox virus (SPPV). In an event of an SPP outbreak, historically disease-free countries would hesitate to use of live vaccines against SPPVdue to the safety and trade reasons. Currently no killed SPPV vaccines are commercially available. In this study, we developed an inactivated Romanian SPPVvaccine and assessed its efficacy and potency in comparison with a live attenuated Romanian SPPV vaccine. Four naive sheep were vaccinated once with the Romanian SPPV live attenuated vaccine and16 sheep were vaccinated twice with the inactivated vaccine. All sheep in the live vaccine group were included in the challenge trial, which was conducted using a highly virulent Moroccan SPPV field strain. Eight sheep of the inactivated vaccine group were challenged and the remaining sheep were monitored for seroconversion. Experimental animals were closely monitored for the appearance of clinical signs, body temperature and inflammation at the injection site. Two naive sheep were used as unvaccinated controls. RESULTS: The inactivated Romanian SPPV vaccine was found to be safe and confer a good protection, similar to the live vaccine. Specific antibodies appeared from seven days post vaccination and remained up to nine months. CONCLUSION: This study showed that the developed inactivated Romanian SPPV vaccine has a potential to replace attenuated vaccine to control and prevent sheep pox in disease-free or endemic countries. PMID- 27357389 TI - Can Destination Therapy be implemented in children with heart failure? A study of provider perceptions. AB - DT is an established final therapeutic choice in adult patients with severe heart failure who do not meet criteria for cardiac transplantation. Patients are given VADs, without the prospect of care escalation to transplantation. VADs are now established therapy for children and are currently used as a bridge until transplantation can be performed or heart failure improves. For children who present in severe heart failure but do not meet transplantation criteria, the question has emerged whether DT can be offered. This qualitative study aimed to elicit the perspectives of early adopters of DT at one of the few institutions where DT has been provided for children. Responses were recorded and coded and themes extracted using grounded theory. Interviewees discussed: envisioning of the DT candidate; approach to evaluation for DT; contraindications to choosing DT; and concerns about choosing DT. Providers articulated two frameworks for conceptualizing DT: as a long bridge through resolution of problems that would initially contraindicate transplantation or, alternatively, as a true destination instead of transplantation. True destination, however, may not be the lasting concept for long-term VAD use in children given improvement in prognosis for current medical contraindications and improving VAD technology. PMID- 27357390 TI - Consomic mouse strain selection based on effect size measurement, statistical significance testing and integrated behavioral z-scoring: focus on anxiety related behavior and locomotion. AB - BACKGROUND: Selecting chromosome substitution strains (CSSs, also called consomic strains/lines) used in the search for quantitative trait loci (QTLs) consistently requires the identification of the respective phenotypic trait of interest and is simply based on a significant difference between a consomic and host strain. However, statistical significance as represented by P values does not necessarily predicate practical importance. We therefore propose a method that pays attention to both the statistical significance and the actual size of the observed effect. The present paper extends on this approach and describes in more detail the use of effect size measures (Cohen's d, partial eta squared - eta p (2) ) together with the P value as statistical selection parameters for the chromosomal assignment of QTLs influencing anxiety-related behavior and locomotion in laboratory mice. RESULTS: The effect size measures were based on integrated behavioral z-scoring and were calculated in three experiments: (A) a complete consomic male mouse panel with A/J as the donor strain and C57BL/6J as the host strain. This panel, including host and donor strains, was analyzed in the modified Hole Board (mHB). The consomic line with chromosome 19 from A/J (CSS 19A) was selected since it showed increased anxiety-related behavior, but similar locomotion compared to its host. (B) Following experiment A, female CSS-19A mice were compared with their C57BL/6J counterparts; however no significant differences and effect sizes close to zero were found. (C) A different consomic mouse strain (CSS-19PWD), with chromosome 19 from PWD/PhJ transferred on the genetic background of C57BL/6J, was compared with its host strain. Here, in contrast with CSS-19A, there was a decreased overall anxiety in CSS-19PWD compared to C57BL/6J males, but not locomotion. CONCLUSIONS: This new method shows an improved way to identify CSSs for QTL analysis for anxiety-related behavior using a combination of statistical significance testing and effect sizes. In addition, an intercross between CSS-19A and CSS-19PWD may be of interest for future studies on the genetic background of anxiety-related behavior. PMID- 27357391 TI - Minocycline attenuates interferon-alpha-induced impairments in rat fear extinction. AB - BACKGROUND: Extinction of conditioned fear is an important brain function for animals to adapt to a new environment. Accumulating evidence suggests that innate immune cytokines are involved in the pathology of psychotic disorders. However, the involvement of cytokines in fear dysregulation remains less investigated. In the present study, we investigated how interferon (IFN)-alpha disrupts the extinction of conditioned fear and propose an approach to rescue IFN-alpha induced neurologic impairment. METHODS: We used a rat model of auditory fear conditioning to study the effect of IFN-alpha on the fear memory process. IFN alpha was infused directly into the amygdala of rats and examined the rats' behavioral response (freezing) to fear-conditioned stimuli. Immunohistochemical staining was used to examine the glia activity status of glia in the amygdala. The levels of the proinflammatory cytokines interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha in the amygdala were measured by enzyme-linked immunosorbent assay. We also administrated minocycline, a microglial activation inhibitor, before the IFN-alpha infusion to testify the possibility to reverse the IFN-alpha-induced effects. RESULTS: Infusing the amygdala with IFN-alpha impaired the extinction of conditioned fear in rats and activated microglia and astrocytes in the amygdala. Administering minocycline prevented IFN-alpha from impairing fear extinction. The immunohistochemical and biochemical results show that minocycline inhibited IFN-alpha-induced microglial activation and reduced IL 1beta and TNF-alpha production. CONCLUSIONS: Our findings suggest that IFN-alpha disrupts the extinction of auditory fear by activating glia in the amygdala and provides direction for clinical studies of novel treatments to modulate the innate immune system in patients with psychotic disorders. PMID- 27357392 TI - Design of a Water Soluble Fluorescent 3-Hydroxy-4-Pyridinone Ligand Active at Physiological pH Values. AB - In the present work we report the structure and the spectroscopic characterization of a new fluorescent 3-hydroxy-4-pyridinone ligand D-3,4-HPO. The synthesis of the compound was performed in two steps, which involve the reaction of the commercially available fluorophore dansyl chloride with a 3 hydroxy-4-pyridinone chelating unit and further deprotection. The new fluorescent chelator was characterized in the solid state by single-crystal X-ray diffraction and in solution by NMR, MS, absorption and fluorescence spectroscopies. The analysis of the variation of the absorption spectrum with pH allowed the determination of four pK a values (pK a1 = 3.50, pK a2 = 4.50, pK a3 = 9.60, pK a4 = 10.20) and establishment of the corresponding distribution diagram. The study of the fluorescence properties of the ligand show that in the pH range between 4 and 9 the fluorescence intensity is constant and has its maximum value thus allowing its further use at physiological pH values. The interaction of the ligand with copper(II) was accessed by fluorescence spectroscopy in MOPS buffer and the results show that the presence of copper(II) quenches the fluorescence of the ligand in ca 94 % at a ligand: metal ratio of 2:1. The latter result is consistent with the formation of a copper(II) complex with the bidentate ligand, as confirmed by the EPR spectroscopy. Graphical Abstract New water soluble fluorescent ligand active at physiological pH values. PMID- 27357393 TI - The Sensitive Turn-On Fluorescence Detection of Ascorbic Acid Based on Iron(III) Modulated Nitrogen-Doped Graphene Quantum Dots. AB - A rapid, selective and sensitive sensor based on the Fe(III) modulated nitrogen doped graphene quantum dots (N-GQDs) was developed and applied as fluorescence sensor for ascorbic acid (AA) detection. The N-GQDs was one-step synthesized in an easy and green way using citric acid as the carbon source and urea as nitrogen source. The sensor was based on the different quenching effects of Fe(III) and Fe(II) on the fluorescence intensity of N-GQDs. The fluorescence of N-GQDs was quenched by Fe(III) via the strong selective coordination interaction between them. In the presence of AA, Fe(III) can be transformed to Fe(II) ascribed to the oxidation-reduction reaction, leading to the recovery of fluorescence. On the basis of this principle, a fluorescence sensor for AA detection was constructed. Under optimal conditions, the method showed a response to AA within a concentration range of 1.0-90 MUmol L(-1) with a good linear relationship and the detection limit for AA was 18 nmol L(-1). The developed sensor was successfully applied for the determination of AA in beverage samples with quantitative recoveries from 95.3 % to 104.3 %. PMID- 27357394 TI - Patient Mobility for Elective Secondary Health Care Services in Response to Patient Choice Policies: A Systematic Review. AB - Our review establishes the empirical evidence for patient mobility for elective secondary care services in countries that allow patients to choose their health care provider. PubMed and Embase were searched for relevant articles between 1990 and 2015. Of 5,994 titles/abstracts reviewed, 26 studies were included. The studies used three main methodological models to establish mobility. Variation in the extent of patient mobility was observed across the studies. Mobility was positively associated with lower waiting times, indicators of better service quality, and access to advanced technology. It was negatively associated with advanced age or lower socioeconomic backgrounds. From a policy perspective we demonstrate that a significant proportion of patients are prepared to travel beyond their nearest provider for elective services. As a consequence, some providers are likely to be "winners" and others "losers," which could result in overall decreased provider capacity or inefficient utilization of existing services. Equity also remains a key concern. PMID- 27357395 TI - Assessment of Angelica sinensis (Oliv.) Diels as a repellent for personal protection against mosquitoes under laboratory and field conditions in northern Thailand. AB - BACKGROUND: Angelica sinensis (Oliv.) hexane extract (AHE) has been reported as a proven and impressive repellent against laboratory-reared female Aedes aegypti mosquitoes. With the aim of promoting products of plant origin as a viable alternative to conventional synthetic substances, this study was designed to transform AHE-based repellents for exploitable commercial production by enhancing their efficacy and assessing their physical and biological stability as well as repellency against mosquitoes under laboratory and field conditions. METHODS: The chemical profile of AHE was analyzed by qualitative gas chromatography-mass spectrometry (GC-MS) technique. AHE was supplemented with vanillin, as a fixative, and then investigated for repellency and comparison to the standard synthetic repellent, DEET, under both laboratory and field conditions. Determination of physical and biological stability as a repellent was carried out after keeping AHE samples under varying temperatures and for different storage times. RESULTS: GC-MS analysis revealed that AHE contained at least 21 phytochemical compounds, constituting 95.74 % of the total content, with the major constituent of 3-N-butylphthalide (66.67 %). Ethanolic formulations of AHE and DEET showed improvement of repellency in a dose-dependent manner when vanillin was added in laboratory assessment. While 5-25 % AHE alone provided median complete-protection times of 2.0-6.5 h against Ae. aegypti, these times were increased to 4.0-8.5 h with a combination of AHE and 5 % vanillin (AHEv). Protection times against Ae. aegypti were extended from 2.25 to 7.25 h to 4.25 8.25 h when 5-25 % DEET was combined with 5 % vanillin (DEETv). In determining stability, all stored AHE samples exhibited similar characteristics such as liquid phases with aromatic odor comparable to those of fresh preparations. Furthermore, repellent activity of stored AHE samples lasted for at least six months, with varied efficacy (4.5-10.0 h) against Ae. aegypti. Field trials revealed strong repellency from both 25 % AHEv and 25 % DEETv, with complete protection (100 %) against a wide range of local mosquito populations. A total of 5,718 adult female mosquitoes, with the most predominant being Culex quinquefasciatus (41.47 %), Armigeres subalbatus (41.13 %), and Culex vishnui (10.53 %), was collected during field applications. No local skin reaction or other allergic responses was observed during both laboratory and field study periods. CONCLUSIONS: Angelica sinensis proved to have not only impressive repellency against both laboratory Ae. aegypti and a wide range of natural mosquito populations, but also relative stability in physical and biological performance. PMID- 27357397 TI - Erratum to: Atraumatic splenic rupture, an underrated cause of acute abdomen. PMID- 27357396 TI - Variants in CCL16 are associated with blood plasma and cerebrospinal fluid CCL16 protein levels. AB - BACKGROUND: CCL16 is a chemokine predominantly expressed in the liver, but is also found in the blood and brain, and is known to play important roles in immune response and angiogenesis. Little is known about the gene's regulation. METHODS: Here, we test for potential causal SNPs that affect CCL16 protein levels in both blood plasma and cerebrospinal fluid in a genome-wide association study across two datasets. We then use METAL to performed meta-analyses with a significance threshold of p < 5x10(-8). We removed SNPs where the direction of the effect was different between the two datasets. RESULTS: We identify 10 SNPs associated with increased CCL16 protein levels in both biological fluids. CONCLUSIONS: Our results will help understand CCL16's regulation, allowing researchers to better understand the gene's effects on human health. PMID- 27357398 TI - A Tale of 3 Trials: ACCORD, SPRINT, and SPS3. What Happened? AB - Within the last several years, the National Institutes of Health has supported three randomized clinical trials to determine whether lower than usually recommended goals for treatment of hypertension would have greater benefit for prevention of cardiovascular disease and stroke. These were the ACCCORD, SPRINT, and Secondary Prevention of Small Subcortical Strokes (SPS3) Trials. Together they enrolled 17,114 participants. Results for all three have been reported. The trials differ from each other in their inclusion criteria, target blood pressures for the lower goal (intensive treatment), but are similar in many respects. The results with regard to their primary outcome were different: not significant for ACCORD and SPS3, but definitely significant for SPRINT. Subgroup analysis revealed differences and similarities. When viewed together and with recent large observational studies, they support a conclusion that a systolic pressure in the range of 125-135 mm Hg range is likely to be optimal on treatment for most hypertensive patients. PMID- 27357399 TI - RNA-binding protein LIN28 is a sensitive marker of pediatric yolk sac tumors. AB - BACKGROUND: RNA-binding protein LIN28 is involved in maintaining the pluripotency of embryonic stem cells. It has been detected in different types of testicular and ovarian germ cell tumors (GCTs), but its status in pediatric YSTs (yolk sac tumors) is still unknown. The aim of this study was to determine the immunohistochemical profile of LIN28 in pediatric YSTs. METHODS AND RESULTS: Immunohistochemistry detection of LIN28 was performed in 22 cases of pediatric YSTs and 10 mature teratomas. The percentage of tumor cells stained was scored as 0, 1+ (1-30 % cells), 2+ (31-60 %), 3+ (61-90 %), and 4+ (>90 %). To compare its sensitive and specificity with alpha-fetoprotein (AFP), we also stained AFP in 22 cases of pediatric YSTs and 10 mature teratomas in children. LIN28 staining was high in all 22 pediatric yolk sac tumor (2+ in 1, 3+ in 1, and 4+ in 20), and weak staining of LIN28 was seen in 1 of 10 mature teratomas (1+), 9 of 10 mature teratomas were negative expression. However, the expression of AFP in pediatric YST was lower compared with Lin28 (- in 1, 1+ in 8, 2+ in 12, and 3+ in 1), and weak expression of AFP was seen in 2 of 10 mature teratomas (1+), 8 of 10 mature teratomas were negative. LIN28 had higher intensity expression than AFP in pediatric YSTs (P < 0.001). CONCLUSIONS: LIN28 is a sensitive marker for pediatric YSTs and it can be used to distinguish them from mature teratomas. LIN28 is likely to become a new and valuable biomarker for diagnosing of pediatric YST. PMID- 27357400 TI - Critical analysis of fecal incontinence scores. AB - INTRODUCTION: Objectively evaluating the lack of bowel control (fecal incontinence) continues to be a challenge. Many have attempted to measure the severity of fecal incontinence and to evaluate its impact on the quality of life by developing standardized scoring systems. Some of these systems have been validated but none have achieved widespread use and all have limitations in evaluating pediatric patients. METHODS: A review of the literature was performed looking for validated scoring systems of fecal incontinence that are currently used for either adult or pediatric patients. The identified scoring systems were then critically analyzed and their applicability for managing fecally incontinent children considered. RESULTS: Thirteen of the most frequently used fecal incontinence scoring systems were selected (6 for adults and 7 for children). Quality of life questionnaires were excluded not only because of their length and complexity, but mostly because they do not accurately reflect a measurement of bowel control. Our analysis revealed that all pediatric scoring systems require some degree of interpretation as they included at least one subjective parameter. These unverifiable subjective parameters were: "sensation of rectal fullness", "sphincter squeeze", and "anal shape". Equally problematic, the pediatric systems frequently focused on factors unrelated to fecal continence such as "frequency of bowel movements", "rectal prolapse", "abdominal pain", "blood in the stool", "leakage of urine", "diarrhea", and "constipation". The most objective system found from our review is the Krickenbeck system, which focuses upon two objective factors. Those two factors are the absence of voluntary bowel movements and the presence of soiling in the underwear. The major weakness of the Krickenbeck system is that it does not allow for reassessment after medical or surgical interventions. In this paper, we propose a modification of the Krickenbeck system that allows for such an assessment to be applied to those patients who are able to achieve voluntary bowel movements with the aid of laxatives or constipating agents. CONCLUSIONS: Most scoring systems are flawed because they invite bias and interpretation due to their subjective nature, while systems focused on measuring quality of life do not address the fundamental issue of bowel control. The Krickenbeck score seems to be the most applicable and objective method of evaluating bowel control in pediatric patients that may be more useful when modified to assess patients after medical intervention. PMID- 27357403 TI - Functional properties of DENV EDIII-reactive antibodies in human DENV-1-infected sera and rabbit antiserum to EDIII. AB - The envelope domain III (EDIII) of the dengue virus (DENV) has been confirmed to be involved in receptor binding. It is the target of specific neutralizing antibodies, and is considered to be a promising subunit dengue vaccine candidate. However, several recent studies have shown that anti-EDIII antibodies contribute little to the neutralizing or enhancing ability of human DENV-infected serum. The present study involved an analysis of the neutralization and antibody-dependent enhancement (ADE) activities of EDIII-reactive antibodies in human convalescent sera from patients with primary DENV-1 infection and rabbit antiserum immunized with recombinant DENV-1 EDIII protein. The results indicated that serum neutralization was not associated with titres of EDIII-binding antibodies in the human DENV-1-infected sera. The depletion of anti-EDIII antibodies from these serum samples revealed that the anti-EDIII antibodies of the patients contributed little to neutralization and ADE. However, the EDIII-reactive antibodies from the rabbit antiserum exhibited protective abilities of neutralization at a high dilution (~1:50,000) and ADE at a low dilution (~1:5,000) for the homotypic DENV infection. Notably, the rabbit antiserum displayed ADE activity only at a dilution of 1:40 for the heterotypic virus infection, which suggests that EDIII reactive antibodies may be safe in secondary infection with heterotypic viruses. These results suggest that DENV EDIII is not the predominant antigen of the DENV infection process; however, purified or recombinant DENV EDIII may be used as a subunit vaccine to provoke an effective and safe antibody response. PMID- 27357401 TI - The effects of different intensities of exercise and active vitamin D on mouse bone mass and bone strength. AB - Physical exercise is beneficial to bone health. However, little is known how different intensities of exercise affect bone mass and strength. In the present study, we used young mice to study the effects of different intensities of exercise on bone mass and bone strength in comparison to pharmacological doses of active vitamin D (calcitriol). We found that only the medium level of exercise tested showed a positive effect on bone mineral density, trabecular bone volume, and bone strength, which are attributable to a decrease in bone resorption and an increase in bone formation, with the latter being accompanied by an increase in the number of osteogenic mesenchymal stem cells in the bone marrow. Calcitriol increases bone volume and bone strength, yet the combination of calcitriol and medium-intensity exercise did not further improve bone mass or strength. Moreover, calcitriol also showed some protective effect on the bone in mice with high levels of exercise. These results indicate that exercise at medium intensity increases bone mass and strength via affecting both bone formation and resorption and that its beneficial effects on bone mass cannot be further improved by calcitriol. PMID- 27357402 TI - Palliative primary tumor resection provides survival benefits for the patients with metastatic colorectal cancer and low circulating levels of dehydrogenase and carcinoembryonic antigen. AB - BACKGROUND: It remains controversial whether palliative primary tumor resection (PPTR) can provide survival benefits to the patients with metastatic colorectal cancer (mCRC) who have unresectable metastases. The aim of this study was to evaluate whether PPTR could improve the survival of patients with mCRC. METHODS: We conducted a retrospective study on consecutive mCRC patients with unresectable metastases who were diagnosed at Sun Yat-sen University Cancer Center in Guangzhou, Guangdong, China, between January 2005 and December 2012. Overall survival (OS) and progression-free survival (PFS) after first-line chemotherapy failure were compared between the PPTR and non-PPTR patient groups. RESULTS: A total of 387 patients were identified, including 254 who underwent PPTR and 133 who did not. The median OS of the PPTR and non-PPTR groups was 20.8 and 14.8 months (P < 0.001), respectively. The median PFS after first-line chemotherapy was 7.3 and 4.8 months (P < 0.001) in the PPTR and non-PPTR groups, respectively. A larger proportion of patients in the PPTR group (219 of 254, 86.2%) showed local progression compared with that of patients in the non-PPTR group (95 of 133, 71.4%; P < 0.001). Only patients with normal lactate dehydrogenase (LDH) levels and with carcinoembryonic antigen (CEA) levels <70 ng/mL benefited from PPTR (median OS, 22.2 months for the PPTR group and 16.2 months for the non-PPTR group; P < 0.001). CONCLUSIONS: For mCRC patients with unresectable metastases, PPTR can improve OS and PFS after first-line chemotherapy and decrease the incidence of new organ involvement. However, PPTR should be recommended only for patients with normal LDH levels and with CEA levels <70 ng/mL. PMID- 27357404 TI - Production and biological activities of yellow pigments from Monascus fungi. AB - Monascus yellow pigments (MYPs), are azaphilone compounds and one of the three main components of total Monascus pigments (MPs). Thirty-five hydrophilic or hydrophobic MYPs have been identified, with the majority being hydrophobic. Apart from screening special Monascus strains, some advanced approaches, such as extractive and high-cell-density fermentations, have been applied for developing or producing new MYPs, especially extracellular hydrophilic MYPs. The outstanding performance of MYPs in terms of resistance to photodegradation, as well as tolerance for temperature and pH, give natural MYPs reasonable prospects, compared with the orange and red MPs, for practical use in the present and future. Meanwhile, MYPs have shown promising potential for applications in the food and pharmaceutical industries based on their described bioactivities. This review briefly summarizes the reports to date on chemical structures, biological activities, biosynthetic pathways, production technologies, and physicochemical performances of MYPs. The existing problems for MYPs are discussed and research prospects proposed. PMID- 27357405 TI - Biodesulfurization: a model system for microbial physiology research. AB - Biological desulfurization (biodesulfurization) of dibenzothiophene (DBT) by the 4S pathway is a model system for an enviromentally benign way to lower the sulfur content of petroleum. Despite a large amount of effort the efficiency of the 4S pathway is still too low for a commercial oil biodesulfurization process, but the 4S pathway could potentially be used now for commercial processes to produce surfactants, antibiotics, polythioesters and other chemicals and for the detoxification of some chemical warfare agents. Proteins containing disulfide bonds are resistant to temperature, pH, and solvents, but the production of disulfide-rich proteins in microbial hosts is challenging. The study of the 4S pathway can provide insights as to how to maximize the production of disulfide rich proteins. Engineering of the operon encoding the 4S pathway to contain a greater content of methionine and cysteine may be able to link use of DBT as a sole sulfur source to increasing 4S pathway activity by increasing the nutritional demand for sulfur. This strategy could result in the development of biocatalysts suitable for use in an oil biodesulfurization process, but the study of the 4S pathway can also lead to a better understanding of microbial physiology to optimize activity of a mult-step co-factor-requiring pathway, as well as the production of highly stable industrially relevant enzymes for numerous applications. PMID- 27357406 TI - Lanthanides: New life metals? AB - Lanthanides (Ln(3+)) that are Rare Earth Elements, until recently thought to be biologically inert, have recently emerged as essential metals for activity and expression of a special type of methanol dehydrogenase, XoxF. As XoxF enzyme homologs are encoded in a wide variety of microbes, including microbes active in important environmental processes such as methane and methanol metabolism, Ln(3+) may represent some of the key biogeochemical drivers in cycling of carbon and other elements. However, significant gaps in understanding the role of Ln(3+) in biological systems remain as the functions of most of the proteins potentially dependent of Ln(3+) and their roles in specific metabolic networks/respective biogeochemical cycles remain unknown. Moreover, enzymes dependent on Ln(3+) but not related to XoxF enzymes may exist, and these so far have not been recognized. Through connecting the recently uncovered genetic divergence and phylogenetic distribution of XoxF-like enzymes and through elucidation of their activities, metal and substrate specificities, along with the biological contexts of respective biochemical pathways, most parsimonious scenarios for their evolution could be uncovered. Generation of such data will firmly establish the role of Ln(3+) in the biochemistry of Life inhabiting this planet. PMID- 27357407 TI - Integration of microalgal cultivation system for wastewater remediation and sustainable biomass production. AB - Untreated wastewaters have been a great concern and can cause major pollution problems for environment. Conventional approaches for treating wastewater involve tremendous capital cost, have major short comings and are not sustainable. Microalgae culture offers an interesting step for wastewater treatment. Microalgae serve the dual purpose of phycoremediation along with the production of potentially valuable biomass, which can be used for several purposes. The ability of microalgae to accumulate nitrogen, phosphorus, heavy metals and other toxic compounds can be integrated with wastewater treatment system to offer an elegant solution towards tertiary and quaternary treatment. The current review explores possible role of microalgal based wastewater treatment and explores the current progress, key challenges, limitations and future prospects with special emphasis on strategies involved in harvesting, boosting biomass and lipid yield. PMID- 27357408 TI - Tillandsia stricta Sol (Bromeliaceae) leaves as monitors of airborne particulate matter-A comparative SEM methods evaluation: Unveiling an accurate and odd HP-SEM method. AB - Airborne particulate matter (PM) has been included among the most important air pollutants by governmental environment agencies and academy researchers. The use of terrestrial plants for monitoring PM has been widely accepted, particularly when it is coupled with SEM/EDS. Herein, Tillandsia stricta leaves were used as monitors of PM, focusing on a comparative evaluation of Environmental SEM (ESEM) and High-Pressure SEM (HPSEM). In addition, specimens air-dried at formaldehyde atmosphere (AD/FA) were introduced as an SEM procedure. Hydrated specimen observation by ESEM was the best way to get information from T. stricta leaves. If any artifacts were introduced by AD/FA, they were indiscernible from those caused by CPD. Leaf anatomy was always well preserved. PM density was determined on adaxial and abaxial leaf epidermis for each of the SEM proceedings. When compared with ESEM, particle extraction varied from 0 to 20% in air-dried leaves while 23-78% of particles deposited on leaves surfaces were extracted by CPD procedures. ESEM was obviously the best choice over other methods but morphological artifacts increased in function of operation time while HPSEM operation time was without limit. AD/FA avoided the shrinkage observed in the air dried leaves and particle extraction was low when compared with CPD. Structural and particle density results suggest AD/FA as an important methodological approach to air pollution biomonitoring that can be widely used in all electron microscopy labs. Otherwise, previous PM assessments using terrestrial plants as biomonitors and performed by conventional SEM could have underestimated airborne particulate matter concentration. PMID- 27357409 TI - Editorial Comment to Does bilateral seminal vesicle invasion at radical prostatectomy predict worse prognosis than unilateral invasion among patients with pT3b prostate cancers? PMID- 27357411 TI - Comprehensive activities to increase recognition of primary immunodeficiency and access to immunoglobulin replacement therapy in Poland. AB - The study presents an overview on current situation of primary immunodeficiency (PID) patients in Poland and the 2014 annual report of the Polish Working Group for Immunodeficiency (PWGID). The group was set up in 2005 to improve diagnosis, treatment, and care of patients with immunodeficiencies and currently includes 15 pediatric and 13 adult centers. According to PWGID report 4099, PID patients are recognized in Poland, with the prevalence 10.6/100,000. The majority of them (54.2 %) have predominantly antibody deficiency (PAD). In 2014 alone, a total number of 731 newly diagnosed individuals are reported. As predicted, the vast majority (70 %) of them have PAD. Approximately one third of PAD patients require immunoglobulin replacement therapy. Within the entire cohort, an intravenous route of immunoglobulin therapy dominates (67.3 %). However, within the age groups, distribution of immunoglobulin therapy varies and seems to be age related. Among children, 36 % receive subcutaneous immunoglobulin, while with adults 26 %. CONCLUSION: Analysis of numbers of either newly recognized or treated patients indicates its dynamic increase in recent years. This is the result of comprehensive activities by PWGID supported by governmental institutions, outstanding foundations, and patient's organization. WHAT IS KNOWN: * Immunoglobulins' treatment has substantially changed the life of individuals with PAD. Patients with common variable immunodeficiency (CVID) or X-linked agammaglobulinemia (XLA) can live and lead a near normal life. Early diagnosis of the disease followed by earlier implementation of appropriate treatment, including gammaglobulin replacement therapy, improves the quality of life. * Targeted efforts of health care professionals and government are required to optimize diagnostic and therapeutic approach for PAD. What is New: * Comprehensive activities of PWGID lead to better recognition of PID individuals and should improve reporting Polish PIDs to the ESID database. * Following the joint efforts of immunologists, patient's, and governmental organizations in the end of 2014, the Therapeutic Program for Treatment Adults with PID was introduced, leading to universal access to currently available treatment options and to improve the quality of life. PMID- 27357410 TI - Magicplex(TM) Sepsis Real-Time test to improve bloodstream infection diagnostics in children. AB - Sepsis is the major cause of morbidity and mortality in children, especially in immunocompromised patients, and a rapid identification of causative pathogen is strongly related with a better outcome. This prospective study analyzes the role of a multiplex real-time polymerase chain reaction in sepsis' etiological diagnosis. Magicplex(TM) Sepsis Real-Time tests were performed in tertiary Regina Margherita Children's Hospital (Turin, Italy), and the medical records of children who underwent a Magicplex test were prospectively evaluated. Results of the Magicplex test were compared with those of blood culture collected at a close time point. One hundred fifty Magicplex tests were collected from 89 patients (54 males and 35 females, age interquartile range: 2.6-12.1 years). Etiological definition was achieved in 60 bloodstream infection cases (40 %). In 32 episodes, Magicplex test alone gave a positive result, and blood culture alone permitted the etiological diagnosis in 5 septic episodes. Magicplex test allowed a 143 % increase in the diagnostic value of blood cultures. CONCLUSION: These results suggest that molecular biology can be useful for rapid pathogen's identification also in children. WHAT IS KNOWN: * Sepsis represents a major cause of morbidity and mortality in children. * Sepsis outcome is strongly related to rapid microbiological identification and prompt initiation of an appropriate chemotherapy. What is New: * This manuscript is the first that describes the use of Magicplex (TM) Sepsis Real-Time test in children. * The results suggest that molecular biology can be useful for rapid pathogen's identification also in children. PMID- 27357412 TI - Owners' attitudes and practices regarding nutrition of dogs diagnosed with cancer presenting at a referral oncology service in Ontario, Canada. AB - OBJECTIVES: To investigate owner attitudes and dietary practices following cancer diagnosis in a dog. METHODS: A retrospective cross-sectional survey of 75 dog owners presenting with their dogs to a tertiary referral oncology service through a demographic questionnaire and in-person or telephone interviews regarding the dog's nutrition. RESULTS: Conventional diets (71%) were most commonly fed as a single diet to canine cancer patients followed by homemade cooked (7%) and homemade raw (4%). Several owners (18%) provided combinations of these diets. Owners reported some distrust towards conventional diets (51%). Appetite loss occurred in 35% of dogs and diet changes reported for 25% of dogs in the study involved exclusion of a conventional (63%) and/or inclusion of a homemade (54%) component. 90% of owners noted the diet change was associated with the cancer diagnosis. Supplements were given by 39% of owners. 85% of owners highly valued veterinary nutritional advice. CLINICAL RELEVANCE: Following a cancer diagnosis, dog owners appear to change their approach to managing their dog's nutrition. Given the value owners place on veterinary nutritional advice, veterinarians have a key role in guiding nutritional management of the canine cancer patient. PMID- 27357413 TI - Accurate Kohn-Sham ionization potentials from scaled-opposite-spin second-order optimized effective potential methods. AB - One important property of Kohn-Sham (KS) density functional theory is the exact equality of the energy of the highest occupied KS orbital (HOMO) with the negative ionization potential of the system. This exact feature is out of reach for standard density-dependent semilocal functionals. Conversely, accurate results can be obtained using orbital-dependent functionals in the optimized effective potential (OEP) approach. In this article, we investigate the performance, in this context, of some advanced OEP methods, with special emphasis on the recently proposed scaled-opposite-spin OEP functional. Moreover, we analyze the impact of the so-called HOMO condition on the final quality of the HOMO energy. Results are compared to reference data obtained at the CCSD(T) level of theory. (c) 2016 Wiley Periodicals, Inc. PMID- 27357414 TI - Guardians of 'the gift': the emotional challenges of heart and lung transplant professionals in Denmark. AB - This paper deals with the emotional challenges encountered by doctors and nurses caring for heart and lung transplant patients. Organ transplantation enables body parts from the dead to become usable in patients with no other life-saving option. These exchanges are not possible without transplant professionals carefully selecting, guiding and interacting with organ recipients before, during and after the transplant. Based on anthropological fieldwork at a Danish heart and lung transplant unit, the paper explores how doctors and nurses experience and handle the emotional challenges of their working life. By focusing on the everyday life of the transplant unit which, contrary to public understanding of transplant miracles, is sometimes characterised by sad cases and devastation, this paper argues that transplant professionals operate in the presence of death. Medically and emotionally they are at risk. They must take the difficult decisions of whether to admit critically ill patients onto the organ waiting list; face the distress of post-transplant sufferings and deaths; and deal with organ recipients who do not behave according to post-transplant recommendations. Drawing on a familiar metaphor for donated organs, it is suggested that transplant doctors and nurses are 'guardians of the gift'. Attention to the emotional burdens and rewards of this particular position enables new understandings of the practices of transplant medicine, of gift exchange theory, and of the role of emotion in medical practice. PMID- 27357415 TI - Multimodality imaging of locally recurrent and metastatic cervical cancer: emphasis on histology, prognosis, and management. AB - The management of recurrent and metastatic cervical cancer is evolving in concert with the available advanced imaging techniques and molecular targeted therapy. The purpose of this review is to provide an overview of imaging and treatment of cervical cancer patients with locoregional recurrence and metastatic disease, with emphasis on characteristic patterns of spread based on histology (squamous cell carcinoma and other subtypes), prognostic factors, diagnosis, and treatment response assessment, as well as updated therapeutic options. PMID- 27357416 TI - Inter-trabecular bone formation: a specific mechanism for healing of cancellous bone. AB - Background and purpose - Studies of fracture healing have mainly dealt with shaft fractures, both experimentally and clinically. In contrast, most patients have metaphyseal fractures. There is an increasing awareness that metaphyseal fractures heal partly through mechanisms specific to cancellous bone. Several new models for the study of cancellous bone healing have recently been presented. This review summarizes our current knowledge of cancellous fracture healing. Methods - We performed a review of the literature after doing a systematic literature search. Results - Cancellous bone appears to heal mainly via direct, membranous bone formation that occurs freely in the marrow, probably mostly arising from local stem cells. This mechanism appears to be specific for cancellous bone, and could be named inter-trabecular bone formation. This kind of bone formation is spatially restricted and does not extend more than a few mm outside the injured region. Usually no cartilage is seen, although external callus and cartilage formation can be induced in meta-physeal fractures by mechanical instability. Inter-trabecular bone formation seems to be less sensitive to anti-inflammatory treatment than shaft fractures. Interpretation - The unique characteristics of inter-trabecular bone formation in metaphyseal fractures can lead to differences from shaft healing regarding the effects of age, loading, or drug treatment. This casts doubt on generalizations about fracture healing based solely on shaft fracture models. PMID- 27357417 TI - GSK-3beta inhibitor attenuates urinary albumin excretion in type 2 diabetic db/db mice, and delays epithelial-to-mesenchymal transition in mouse kidneys and podocytes. AB - The mechanism underlying epithelial-to-mesenchymal transition (EMT) caused by high glucose (HG) stimulation in diabetic nephropathy (DN) remains to be fully elucidated. The present study investigated the effects of HG on EMT and the activity of glycogen synthase kinase 3beta (GSK-3beta) in podocytes and the kidneys of db/db mice, and assessed the effects of (2'Z, 3'E)-6-bromoindirubin-3' oxime (BIO), an inhibitor of GSK-3beta, on EMT and glomerular injury. The resulting data showed that the activity of GSK-3beta was upregulated by HG and downregulated by BIO in the podocytes and the renal cortex. The expression levels of epithelial markers, including nephrin, podocin and synaptopodin, were decreased by HG and increased by BIO, whereas the reverse were true for mesenchymal markers, including alpha-smooth muscle actin (alpha-SMA) and fibronectin. The expression levels of beta-catenin and Snail, in contrast to current understanding of the Wnt signaling pathway, were increased by HG and decreased by BIO. In addition, expression of the vitamin D receptor (VDR) was decreased by HG and increased by BIO. In conclusion, the present study revealed that the mechanism by which BIO inhibited HG-mediated EMT in podocytes and the renal cortex was primarily due to the VDR. Treatment with BIO protected renal function by maintaining the integrity of the filtration membrane and decreasing UAE, but not by regulating blood glucose. Therefore, GSK-3beta may be used as a sensitive biomarker of DN, and its inhibition by BIO may be effective in the treatment of DN. PMID- 27357418 TI - Characterization of human bone morphogenetic protein gene variants for possible roles in congenital heart disease. AB - Congenital heart disease (CHD) is a complex illness with high rates of morbidity and mortality. In embryonic development, the heart is the first formed organ, which is strictly controlled by gene regulatory networks, including transcription factors, signaling pathways, epigenetic factors and microRNAs. Bone morphogenetic protein (BMP)-2 and -4 are essential in cardiogenesis as they can induce the expression of transcription factors, NKX2-5 and GATA binding protein 4, which are important in the development of the heart. The inhibition of BMP-2 and -4 inhibits the late expression of NKX2-5 and affects cardiac differentiation. The aim of the present study was to investigate whether BMP-2 and -4 variations may be associated with CHD in Chinese Han populations. The rs1049007, rs235768 and rs17563 single nucleotide polymorphisms (SNPs), which are genetic variations located within the translated region of the BMP-2 and -4, were evaluated in 230 patients with CHD from the Chinese Han population and 160 non-CHD control individuals. Statistical analyses were performed using the chi2 test, implemented using SPSS software (version 13.0). The Hardy-Weinberg equilibrium test was performed on the population using online Online Encyclopedia for Genetic Epidemiology studies software, and multiple-sequence alignments of the BMP proteins were performed using Vector NTI software. No statistically significant associations were identified between these genetic variations and the risk of CHD (rs1049007, P-value=0.560; rs235768, P-value=0.972; rs17563, P-value=0.787). In addition, no correlation was found between the patients with CHD and the non-CHD control individuals. Therefore, the rs1049007, rs235768 and rs17563 genetic variations of BMP-2 were not associated with CHD in the Chinese Han population. PMID- 27357419 TI - miR-20a induces cisplatin resistance of a human gastric cancer cell line via targeting CYLD. AB - The dysregulation of microRNAs (miRNAs) has been demonstrated to contribute to drug resistance of cancer cells, and sustained nuclear factor (NF)kappaB activation is also pivotal in tumor resistance to chemotherapy. In the present study, an essential role for miRNA (miR)-20a was identified in the regulation of gastric cancer (GC) chemoresistance. The expression level of miR-20a was assayed by reverse transcription-quantitative polymerase chain reaction. Additionally, 3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to detect the drug-resistance phenotype changes of cancer cells associated with upregulation or downregulation of miR-20a. Protein expression levelss were measured by western blotting and immunohistochemistry. Flow cytometry was used to detect cisplatin induced apoptosis. It was found that miR-20a was markedly upregulated in GC plasma and tissue samples. Additionally, miR-20a was upregulated in GC plasma and tissues from patients with cisplatin (DDP) resistance, and in the DPP-resistant gastric cancer cell line (SGC7901/DDP). The expression of miR-20a was inversely correlated with the expression of cylindromatosis (CYLD). Subsequently, the assessment of luciferase activity verified that CYLD was a direct target gene of miR-20a. Treatment with miR-20a inhibitor increased the protein expression of CYLD, downregulated the expression levels of p65, livin and survivin, and led to a higher proportion of apoptotic cells in the SGC7901/DDP cells. By contrast, ectopic expression of miR-20a significantly repressed the expression of CYLD, upregulated the expression levels of p65, livin and survivin, and resulted in a decrease in the apoptosis induced by DDP in the SGC7901 cells. Taken together, the results of the present study suggested that miR-20a directly repressed the expression of CYLD, leading to activation of the NFkappaB pathway and the downstream targets, livin and survivin, which potentially induced GC chemoresistance. Altering miR-20a expression may be a potential therapeutic strategy for the treatment of chemoresistance in GC in the future. PMID- 27357420 TI - Physicochemical and Preclinical Evaluation of a Novel Buccal Measles Vaccine. AB - The aim of this study is to develop an orally disintegrating film (ODF) containing a microparticulate measles vaccine formulation for buccal delivery. The measles vaccine microparticles were made with biocompatible and biodegradable bovine serum albumin (BSA) and processed by spray drying. These vaccine microparticles were incorporated in the ODF, consisting of Lycoat RS720(r), Neosorb P60W(r) and Tween 80. The yield of the microparticles was approximately 85-95%, w/w. The mean size of the vaccine microparticles was 3.65 +/- 1.89 MUm and had a slightly negative surface charge of 32.65 +/- 2.4 mV. The vaccine particles were nontoxic to normal cells at high concentrations (500 MUg/2.5 * 105 cells) of vaccine particles. There was a significant induction of innate immune response by vaccine microparticles which was observed in vitro when compared to blank microparticles (P < 0.05). The vaccine microparticles also significantly increased the antigen presentation and co-stimulatory molecules expression on antigen presenting cells, which is a prerequisite for Th1 and Th2 immune responses. When the ODF vaccine formulation was dosed in juvenile pigs, significantly higher antibody titers were observed after week 2, with a significant increase at week 4 and plateauing through week 6 comparative to naive predose titers. The results suggest that the ODF measles vaccine formulation is a viable dosage form alternative to noninvasive immunization that may increase patient compliance and commercial distribution. PMID- 27357421 TI - Rheological Characterization of Ethylcellulose-Based Melts for Pharmaceutical Applications. AB - Rheological characterization of ethylcellulose (EC)-based melts intended for the production, via micro-injection moulding (MUIM), of oral capsular devices for prolonged release was carried out. Neat EC, plasticized EC and plasticized EC containing solid particles of a release modifier (filler volume content in the melt around 30%) were examined by capillary and rotational rheometry tests. Two release modifiers, differing in both chemical nature and particle geometry, were investigated. When studied by capillary rheometry, neat EC appeared at process temperatures as a highly viscous melt with a shear-thinning characteristic that progressively diminished as the apparent shear rate increased. Thus, EC as such could not successfully be processed via MUIM. Plasticization, which induces changes in the material microstructure, enhanced the shear-thinning characteristic of the melt and reduced considerably its elastic properties. Marked wall slip effects were noticed in the capillary flow of the plasticized EC based melts, with or without release modifier particles. The presence of these particles brought about an increase in viscosity, clearly highlighted by the dynamic experiments at the rotational rheometer. However, it did not impair the material processability. The thermal and rheological study undertaken would turn out a valid guideline for the development of polymeric materials based on pharma grade polymers with potential for new pharmaceutical applications of MUIM. PMID- 27357422 TI - Application of Tryptophan Fluorescence Bandwidth-Maximum Plot in Analysis of Monoclonal Antibody Structure. AB - Monoclonal antibodies have become the fastest growing protein therapeutics in recent years. The stability and heterogeneity pertaining to its physical and chemical structures remain a big challenge. Tryptophan fluorescence has been proven to be a versatile tool to monitor protein tertiary structure. By modeling the tryptophan fluorescence emission envelope with log-normal distribution curves, the quantitative measure can be exercised for the routine characterization of monoclonal antibody overall tertiary structure. Furthermore, the log-normal deconvolution results can be presented as a two-dimensional plot with tryptophan emission bandwidth vs. emission maximum to enhance the resolution when comparing samples or as a function of applied perturbations. We demonstrate this by studying four different monoclonal antibodies, which show the distinction on emission bandwidth-maximum plot despite their similarity in overall amino acid sequences and tertiary structures. This strategy is also used to demonstrate the tertiary structure comparability between different lots manufactured for one of the monoclonal antibodies (mAb2). In addition, in the unfolding transition studies of mAb2 as a function of guanidine hydrochloride concentration, the evolution of the tertiary structure can be clearly traced in the emission bandwidth-maximum plot. PMID- 27357423 TI - Nebivolol-Loaded Microsponge Gel for Healing of Diabetic Wound. AB - An attempt was made to formulate nebivolol-loaded microsponge gel to access drug at wound area, incorporated into gel that possess optimum moist wound management environment during later stages of wound closure. Nebivolol, antihypertensive drug, exhibits vasodilating effects via nitric oxide pathway, slows diabetic neuropathy, and restores endothelial function in diabetic wounds. Microsponges were prepared by optimizing independent variables; drug to polymer ratio and internal phase volume and their effects on production yield, entrapment efficiency, and particle size. Formulations of microsponges were evaluated for drug content. Differential scanning calorimetry indicated reduction in crystallinity of NB during the formation of microsponges. In vitro study (drug to polymer 1:4 and 10 ml internal phase volume acetone) showed 80% drug released within 8 h. Spherical and porous microsponges confirmed by scanning electron microscopy were incorporated in the carbopol 934 (2%) gel base. Gel was characterized for pH, viscosity, and drug content. Less spreadability determined by texture analyzer demonstrated viscous nature of gel. In vitro diffusion study revealed entrapped drug in porous microsponges with slow release to heal wound. In vivo study performed using streptozotocin-induced diabetic rats and excision wound model showed wound healing and closure activity within day 10. Histology revealed inflammatory cell infiltrations and neovascularization in granulation tissues, ultimately healing wound. Microsponge gel prolonged drug release due to entrapped form in porous structure of microsponges with significant and fast wound healing and closure in diabetic rats. Microsponges with loaded drug fulfilled accessibility at wound area, while gel provided optimum moist wound management environment during later stages of wound closure. PMID- 27357424 TI - Trial Promoter: A Web-Based Tool for Boosting the Promotion of Clinical Research Through Social Media. AB - BACKGROUND: Scarce information about clinical research, in particular clinical trials, is among the top reasons why potential participants do not take part in clinical studies. Without volunteers, on the other hand, clinical research and the development of novel approaches to preventing, diagnosing, and treating disease are impossible. Promising digital options such as social media have the potential to work alongside traditional methods to boost the promotion of clinical research. However, investigators and research institutions are challenged to leverage these innovations while saving time and resources. OBJECTIVE: To develop and test the efficiency of a Web-based tool that automates the generation and distribution of user-friendly social media messages about clinical trials. METHODS: Trial Promoter is developed in Ruby on Rails, HTML, cascading style sheet (CSS), and JavaScript. In order to test the tool and the correctness of the generated messages, clinical trials (n=46) were randomized into social media messages and distributed via the microblogging social media platform Twitter and the social network Facebook. The percent correct was calculated to determine the probability with which Trial Promoter generates accurate messages. RESULTS: During a 10-week testing phase, Trial Promoter automatically generated and published 525 user-friendly social media messages on Twitter and Facebook. On average, Trial Promoter correctly used the message templates and substituted the message parameters (text, URLs, and disease hashtags) 97.7% of the time (1563/1600). CONCLUSIONS: Trial Promoter may serve as a promising tool to render clinical trial promotion more efficient while requiring limited resources. It supports the distribution of any research or other types of content. The Trial Promoter code and installation instructions are freely available online. PMID- 27357425 TI - Nationwide survey for current clinical status of amniocentesis and maternal serum marker test in Japan. AB - Prenatal testing has been provided in Japan over the past several decades. However, it is difficult to assess the clinical status of amniocentesis (AC) and maternal serum markers (MSM) because obstetricians can perform these tests without registration. This study aims to investigate the current clinical status of AC and MSM in Japan. We conducted a questionnaire study that was intended for a total of 5622 Japanese obstetrics/gynecology facilities during October 2013 to January 2014. The response rate was 40.8% (2295/5622). Of the 2295 facilities, 864 performed MSM (37.7%), 619 performed AC (27.0%) and 412 performed both (18.0%). The average number of MSM tests was 2.0 per month (range 0-52), and the average number of AC tests was 2.4 per month (range 0-30). Involvement of genetic professionals, such as clinical geneticists (CGs) and certified genetic counselors (CGCs), contribute to a content-rich explanation and management of difficult issues and lengthened the explanation time. Nevertheless, relatively few facilities employed these specialists (MSM: 96/864 and AC: 128/619). This is the first study to highlight the current clinical status of AC and MSM tests in Japan. Active involvement of CGs and CGCs can provide more appropriate genetic counseling for prenatal tests. PMID- 27357426 TI - HDR: a statistical two-step approach successfully identifies disease genes in autosomal recessive families. AB - In the search for sequence variants underlying disease, commonly applied filtering steps usually result in a number of candidate variants that cannot further be narrowed down. In autosomal recessive families, disease usually occurs only in one generation so that genetic linkage analysis is unlikely to help. Because homozygous recessive mutations tend to be inherited together with flanking homozygous variants, we developed a statistical method to detect pathogenic variants in autosomal recessive families: We look for differences in patterns of homozygosity around candidate variants between patients and control individuals and expect that such differences are greater for pathogenic variants than random candidate variants. In six autosomal recessive mitochondrial disease families, in which pathogenic homozygous variants have already been identified, our approach succeeded in prioritizing pathogenic mutations. Our method is applicable to single patients from recessive families with at least a few dozen control individuals from the same population; it is easy to use and is highly effective for detecting causative mutations in autosomal recessive families. PMID- 27357427 TI - A replication study of a candidate locus for follicle-stimulating hormone levels and association analysis for semen quality traits in Japanese men. AB - In men, follicle-stimulating hormone (FSH) acts on the seminiferous tubules and enhances spermatogenesis. Recently, a candidate locus (rs2414095) for FSH levels was identified by a genome-wide association study (GWAS) in Chinese men. The rs2414095 single-nucleotide polymorphism (SNP) is found on the third intron of the cytochrome P450, family 19, subfamily A, peptide 1 (CYP19A1) gene encoding an aromatase. In the present study, we performed a replication study in 1687 Japanese men (901 from cohort 1 and 786 from cohort 2) to assess whether this SNP is associated with circulating FSH levels. Furthermore, we investigated whether the rs2414095 SNP is correlated with semen quality traits in 2015 Japanese men (1224 from cohort 1 and 791 from cohort 2). The rs2414095 SNP was significantly associated with circulating FSH levels (betaSTD=0.15, P=9.7 * 10-5), sperm concentration (betaSTD=0.073, P=0.032) and total sperm number (TSN) (betaSTD=0.074, P=0.027) in a combined analysis of the two Japanese male cohorts. We successfully replicated, in Japanese men, the results of the previous GWAS for the rs2414095 SNP in Chinese men, and found that the rs2414095 SNP was related with sperm production. PMID- 27357428 TI - Target resequencing of neuromuscular disease-related genes using next-generation sequencing for patients with undiagnosed early-onset neuromuscular disorders. AB - Neuromuscular disorders are clinically and genetically heterogeneous diseases with broadly overlapping clinical features. Progress in molecular genetics has led to the identification of numerous causative genes for neuromuscular disorders, but Sanger sequencing-based diagnosis remains labor-intensive and expensive because the genes are large, the genotypes and phenotypes of neuromuscular disorders overlap and multiple genes related to a single phenotype exist. Recently, the advent of next-generation sequencing (NGS) has enabled efficient, concurrent examination of several related genes. Thus, we used NGS for target resequencing of neuromuscular disease-related genes from 42 patients in whom undiagnosed early-onset neuromuscular disorders. Causative genes were identified in 19/42 (45.2%) patients (six, congenital muscular dystrophy; two, Becker muscular dystrophy (BMD); three, limb-girdle muscular dystrophy; one, concurrent BMD and Fukuyama congenital muscular dystrophy; three, nemaline myopathy; one, centronuclear myopathy; one, congenital fiber-type disproportion; one, myosin storage myopathy; and one, congenital myasthenic syndrome). We detected variants of uncertain significance in two patients. In 6/19 patients who received a definitive diagnosis, the diagnosis did not require muscle biopsy. Thus, for patients with suspected neuromuscular disorders not identified using conventional genetic testing alone, NGS-based target resequencing has the potential to serve as a powerful tool that allows definitive diagnosis. PMID- 27357431 TI - Altered regulatory T cell phenotype in latent autoimmune diabetes of the adults (LADA). AB - Latent autoimmune diabetes of the adults (LADA) accounts for up to 12% of all patients with diabetes. Initially the disease resembles type 2 diabetes (T2D); however, the typical presence of beta cell autoantibodies indicates an autoimmune basis of LADA. While dysfunctional regulatory T cells (Tregs ) have been implicated in autoimmune diabetes, these cells have been scarcely studied in LADA. The aim of this study was to investigate the frequency and phenotype of circulating Tregs in LADA patients early during disease progression. Flow cytometric analysis was performed on whole blood and peripheral mononuclear cells (PBMC) from patients diagnosed with LADA prior to insulin deficiency (n = 39) and from healthy volunteers (n = 20). Overall, we found the frequency and activation status of peripheral putative Tregs to be altered in LADA patients compared to healthy controls. While total T cells and CD4(+) T cells expressing high levels of CD25 (CD4(+) CD25(hi) ) were unchanged, the frequency and total numbers of CD4(+) T cells expressing an intermediate level of CD25 (CD4(+) CD25(int) ) were decreased in LADA patients. Interestingly, the expression of the Treg -specific marker forkhead box protein 3 (FoxP3), as well as the activation and memory makers CD69, cytotoxic T lymphocyte associated antigen 4 (CTLA-4), CCR4 and CD45RO were increased in CD4(+) CD25(+) T cells of the patients. Our data depict phenotypical changes in T cells of LADA patients that may reflect a derangement in peripheral immune regulation contributing to the slow process leading to insulin-dependent diabetes in these patients. PMID- 27357429 TI - Aberrantly expressed microRNAs in bladder cancer and renal cell carcinoma. AB - Bladder cancer (BC) and renal cell carcinoma (RCC) are frequently diagnosed urinary tract cancers. Recently developed molecular-targeted therapies for RCC have shown remarkable therapeutic efficacy; however, no targeted therapeutics are currently approved for the treatment of BC, and few effective treatment options exist. Current studies have shown that small noncoding RNA molecules have major roles in cancer cells. MicroRNAs (miRNAs) are endogenous small noncoding RNA molecules that regulate protein-/nonprotein-coding RNAs in human cells. A large body of evidence suggests that aberrantly expressed miRNAs are deeply involved in the pathogenesis of human cancers. In this paper, we review recently published miRNA expression signatures of BC and RCC. We focus on downregulated or upregulated miRNAs in multiple signatures and discuss putative target genes of miRNAs. Comparisons of RCC and BC expression signatures revealed that the two types of cancer showed opposite expression patterns for miR-200 family miRNAs (i.e., miR-141/200c and miR-200a/200b/429). We discuss in silico analysis of genes targeted by miR-200 family miRNAs and the molecular mechanisms underlying BC and RCC. PMID- 27357432 TI - N-Heterocyclic Olefins as Robust Organocatalyst for the Chemical Conversion of Carbon Dioxide to Value-Added Chemicals. AB - In this report, the activity of N-heterocyclic olefins (NHOs) as a newly emerging class of organocatalyst is investigated for the chemical fixation of carbon dioxide through reactions with aziridines to form oxazolidinones and the N formylation of amines with polymethylhydrosiloxane (PMHS) or 9 borabicyclo[3.3.1]nonane (9-BBN) as the reducing agent under mild conditions. The exocyclic carbon atoms of NHOs are highly nucleophilic owing to the electron donating ability of the two nitrogen atoms. This high nucleophilicity of the NHOs activates CO2 molecules to form zwitterionic NHO-carboxylate (NHO-CO2 ) adducts, which are active in formylation reactions as well as the carboxylation of aziridines to oxazolidinones. PMID- 27357433 TI - Dipole correlation effects on the local field and the effective dielectric constant in composite dielectrics containing high-k inclusions. AB - Mixing dielectric polymers with high permittivity (high-k) inclusions can affect their electrical properties. In actuation applications of dielectric elastomers, the polarized inclusions generate additional volume polarization-related electrostriction. In energy storage applications, it is possible to store more energy in dielectric composites because of additional polarization of the inclusions and interfaces. However, mixing an electroactive polymer with high-k inclusions also brings several disadvantages. The expulsion of the field from the interior of high-k fillers and the presence of two poles on the filler surface along the applied field direction result in higher local fields EL near the inclusion poles. The resulting field enhancement lowers the breakdown field (Eb) threshold for the material and therefore compromises the actuation and energy storage capabilities of dielectric composites. To mitigate this issue, the dependence of EL on the morphology of inclusion distribution, the field localization effect in chained configurations, and the role of the dipole-dipole correlation effects in the enhancement of the dipolar field of inclusions are analyzed. We show that the dipolar correlation effects are strong in large inclusion composites and their contribution to the inclusion dipole moment MU and to the local fields EL can reach 30-50%. A new method for deriving the composite permittivity from the field EL distribution, based on a caged probe technique, is also presented. PMID- 27357434 TI - Timing of Staged Percutaneous Coronary Intervention for a Non-Culprit Lesion in Patients With Anterior Wall ST Segment Elevation Myocardial Infarction With Multiple Vessel Disease. AB - The optimal timing of a staged percutaneous coronary intervention (PCI) for non culprit lesions in patients with STsegment elevation myocardial infarction (STEMI) patients with multi-vessel disease (MVD) remains controversial. We focused on patients with anterior wall STEMI with MVD and determined the clinical effects for timing of staged PCI.From November 2005 to December 2014, 258 patients were diagnosed with anterior wall STEMI with MVD in our hospital. Among them, 37 patients received staged PCI within 3 weeks, 50 patients received staged PCI during 3 weeks to one year, and 167 patients received only primary PCI for culprit lesions. Clinical outcomes such as admission for angina or heart failure, target vessel revascularization, myocardial infarction, stroke, cardiovascular mortality, and allcause mortality were compared among the 3 groups.Acute kidney injury (AKI) after PCI occurred in 18.9% of the 3-week group, 0% of the one-year group, and 7.6% of the control group (P = 0.005). Of the one-year and 3-year clinical outcomes, the one-year group had better results, such as fewer major adverse cardiac cerebral events (P = 0.028, P = 0.023), and lower recurrent MI (P = 0.065; P = 0.018), cardiovascular mortality (P = 0.043; P = 0.020), and all cause mortality (P = 0.047; P = 0.005).In patients with anterior wall STEMI with MVD, staged PCI for a non-culprit lesion over 3 weeks to one year had a better clinical outcome. Staged PCI for a non-culprit lesion within 3 weeks may be related to the occurrence of AKI, may lead to worse clinical outcomes, and did not decrease the occurrence of angina or post-MI heart failure. PMID- 27357435 TI - Severe Mechanical Hemolysis After Transcatheter Closure of a Traumatic Ventricular Septal Defect Using the Amplatzer Atrial Septal Occluder. AB - Traumatic ventricular septal defect (VSD) resulting from chest trauma, either penetrating or blunt, is a relatively rare occurrence. Herein, we describe the case of a previously healthy 26-year-old man who presented with congestive heart failure, which was secondary to a large traumatic VSD following violent blunt chest trauma. The traumatic VSD was initially closed percutaneously using an Amplatzer atrial septal defect occluder. Post-device closure, however, the patient developed severe intravascular hemolysis refractory to medical treatment. The patient subsequently underwent surgical removal of the Amplatzer device, with concomitant VSD patch closure. PMID- 27357436 TI - Prognostic Value of Major Cardiac Event Risk Score Estimated With Gated Myocardial Perfusion Imaging in Japanese Patients With Coronary Artery Disease. AB - We published a cardiac event risk score (CERS) predicting the risk of major cardiac events (MCEs) within 3 years. The purpose of this study was to verify the prognostic value of the CERS before and after treatment in Japanese patients with coronary artery disease.We retrospectively investigated 612 patients who underwent rest (201)Tl and stress (99m)Tc-tetrofosmin myocardial perfusion single photon emission computed tomography (SPECT) between October 2004 and March 2013 and who had a significant stenosis with >= 75% narrowing of the arterial diameter detected by coronary angiography performed after confirmation of >= 5% ischemia with the SPECT. The patients underwent treatment including revascularization and medication, and thereafter, were re-evaluated with SPECT during a chronic phase and followed-up to confirm prognosis for >= 1 year. The endpoint was the onset of MCEs during the follow-up.During the follow-up (36.7 +/- 14.5 months), 50 patients (8.7%) experienced MCEs comprising cardiac death (n = 16), non-fatal myocardial infarction (n = 4), and unstable angina pectoris (n = 30). The multivariate Cox proportional hazards regression model analysis for the actual occurrence of MCEs showed the summed difference score % and MCE risks estimated with the CERS after treatment to be significant independent variables. Ischemic reduction after treatment contributed significantly to a decrease in the MCE risks. The MCE risks estimated with the CERS after treatment were generally consistent with the incidence of the MCEs actually observed.The CERS after treatment is a valuable formula for predicting prognosis in Japanese patients with coronary artery disease. PMID- 27357438 TI - A Novel Wiring Technique to Insert a Retrograde Guidewire Directly Into the Antegrade Guiding Catheter at the Ascending Aorta for Retrograde Percutaneous Recanalization of an Ostial Coronary Total Occlusion. AB - In recent years, the use of a retrograde approach has become a common practice in the treatment of chronic total occlusion (CTO) of the coronary ostium and artery with an anomalous origin. Use of this approach has increased the chances of a successful percutaneous coronary intervention (PCI). However, the approach requires capturing the retrograde guidewire within the aorta, which can often pose a problem. Therefore, we developed a technique in which the retrograde guidewire is passed through the CTO and inserted directly into the antegrade guiding catheter in the ascending aorta. This technique enabled the successful treatment of the ostial CTO of the right coronary artery using retrograde PCI. PMID- 27357437 TI - Evaluation of Intravascular Hemolysis With Erythrocyte Creatine in Patients With Aortic Stenosis. AB - Chronic intravascular hemolysis has been identified in patients with cardiac valve prostheses, but only a few case reports have evaluated intravascular hemolysis in patients with native valvular heart disease. To detect intravascular hemolysis in patients with aortic stenosis, erythrocyte creatine was evaluated with hemodynamic indices obtained by echocardiography.Erythrocyte creatine, a marker of erythrocyte age, was assayed in 30 patients with aortic stenosis and 10 aged matched healthy volunteers. Peak flow velocity of the aortic valve was determined by continuous-wave Doppler echocardiography. Twenty of 30 patients with aortic stenosis had high erythrocyte creatine levels (> 1.8 umol/g Hb) and erythrocyte creatine was significantly higher as compared with control subjects (1.98 +/- 0.49 versus 1.52 +/- 0.19 umol/g Hb, P = 0.007). Peak transvalvular pressure gradient ranged from 46 to 142 mmHg and peak flow velocity ranged from 3.40 to 5.95 m/second. Patients with aortic stenosis had a significantly lower erythrocyte count (387 +/- 40 versus 436 +/- 42 * 10(4) uL, P = 0.002) and hemoglobin (119 +/- 11 versus 135 +/- 11 g/L, P < 0.001) as compared with control subjects. Erythrocyte creatine had a fair correlation with peak flow velocity (r = 0.55, P = 0.002).In conclusion, intravascular hemolysis due to destruction of erythrocytes was detected in patients with moderate to severe aortic stenosis and the severity of intravascular hemolysis was related to valvular flow velocity of the aortic valve. PMID- 27357440 TI - Exogenous Hydrogen Sulfide Postconditioning Protects Isolated Rat Hearts From Ischemia/Reperfusion Injury Through Sirt1/PGC-1alpha Signaling Pathway. AB - Sirt1 is a highly conserved nicotinamide adenine dinucleotide (NAD(+)) dependent histone deacetylase which plays an important role in heart diseases. Studies performed with Sirt1 activators indicated that it protects cells from ischemia/ reperfusion (I/R) injury. The protective effects of H2S against I/R injury also have been recognized. Hence, the present study was designed to explore whether Sirt1/PGC-1alpha participates in the protection of exogenous H2S postconditioning against I/R injury in isolated rat hearts. Isolated rat hearts were subjected to 30 minutes of global ischemia followed by 60 minutes of reperfusion after 20 minutes of equilibrium. During this procedure, the hearts were exposed to NaHS (10 MUmol/L) treatment in the absence or presence of the selective Sirt1 inhibitor EX-527 (10 MUmol/L). NaHS exerted a protective effect on isolated rat hearts subjected to I/R, as shown by the improved expression of Sirt1/PGC-1alpha associated with restoration of Sirt1 nuclear localization, cardiac function, decreased myocardial infarct size, decreased myocardial enzyme release, and several biochemical parameters, including up-regulation of the ATP and SOD levels, and down-regulation of the MDA level. However, treatment with EX-527 could partially prevent the above effects of NaHS postconditioning. These results indicate that H2S confers protective effects against I/R injury through the activation of Sirt1/PGC1alpha. PMID- 27357439 TI - Response Prediction and Influence of Tolvaptan in Chronic Heart Failure Patients Considering the Interaction of the Renin-Angiotensin-Aldosterone System and Arginine Vasopressin. AB - The renin-angiotensin-aldosterone system (RAAS) and arginine vasopressin (AVP) regulate body fluids. Although conventional diuretics have been used for treating heart failure, they activate RAAS and exacerbate renal function. Tolvaptan, a newly developed vasopressin-2 receptor antagonist, elicits aquaresis and improves volume overload in heart failure patients, however, the predictors of tolvaptan effectiveness and the influence on the RAAS and renal function according to tolvaptan therapy are not established. We evaluated 26 chronic heart failure patients receiving therapy with 15 mg/day tolvaptan and examined their laboratory and urinary data before and after tolvaptan therapy. A response to tolvaptan was defined as a body weight decrease by more than 2 kg in a week and a urine volume increase by 500 mL/ day compared with that before tolvaptan administration. Body weight, urine volume, and brain natriuretic peptide levels significantly improved (P < 0.05), without any worsening of renal function represented by serum creatinine, sodium, and potassium. Moreover, no significant changes were observed in the plasma renin activity and plasma aldosterone concentration (PAC). In the responder group, urine osmolality before tolvaptan administration was significantly higher (P < 0.05) but declined significantly after tolvaptan administration (P < 0.05). The AVP/PAC ratio before administration was positively correlated with the efficacy of tolvaptan. Tolvaptan treatment could prevent RAAS activation in chronic heart failure patients. Moreover, monitoring the AVP/PAC ratio may be useful in predicting the tolvaptan response. PMID- 27357441 TI - Cyclosporin A Protects H9c2 Cells Against Chemical Hypoxia-Induced Injury via Inhibition of MAPK Signaling Pathway. AB - This study aimed to investigate the effects and molecular mechanism of cyclosporin A (CsA) on cobalt chloride (CoCl2)-induced injury in H9c2 embryonic rat cardiac cells. The results showed that CsA could protect H9c2 cells against CoCl2-induced hypoxic injury. CsA effectively improved cell viability, and decreased LDH leakage, cell apoptosis, MDA concentration, and ROS generation, and increased SOD activity, GSH production, and CAT activity in a dosedependent manner. In addition, CsA treatment blocked the CoCl2-induced increases in ROS production and mitochondrial dysfunction, including a decrease in membrane potential, cytochrome c (cyto-c) release, Bax/Bcl-2 imbalance, as well as the ratios of cl-casp-9/casp-9 and cl-casp-3/casp-3 ratios, via the inhibition of p38 and ERK MAPK signaling pathways. The results also suggested that CsA protected H9c2 cells against CoCl2-induced hypoxic injury, possibly by suppressing the MAPK signaling pathway. Thus, CsA is a potential therapeutic agent for cardiac hypoxic injury. PMID- 27357442 TI - Chemically driven negative linear compressibility in sodium amidoborane, Na(NH2BH3). AB - Over the past few years we have been witnessing a surge of scientific interest to materials exhibiting a rare mechanical effect such as negative linear compressibility (NLC). Here we report on strong NLC found in an ionic molecular crystal of sodium amidoborane (NaAB) - easily-accessible, optically transparent material. In situ Raman measurements revealed abnormal elongation of B-N and N-H bonds of NaAB at pressure about 3 GPa. Ab initio calculations indicate the observed spectroscopic changes are due to an isostructural phase transition accompanied by a stepwise expansion of the crystal along c axis. Analysis of calculated charge density distribution and geometry of molecular species (NH2BH3) univocally points to a chemically driven mechanism of NLC - pressure-induced formation of hydrogen bonds. The new H-bond acts as a "pivot screw" coupling N-H covalent bonds of neighbor molecular species - a system resembling a two-lever "jack device" on a molecular scale. A mechanism based on formation of new bonds stands in apparent contrast to mechanisms so far reported in majority of NLC materials where no significant alteration of chemical bonding was observed. The finding therefore suggests a qualitatively new direction in exploration the field towards rational design of incompressible materials. PMID- 27357443 TI - The efficacy and safety of everolimus for the treatment of progressive gastroenteropancreatic neuroendocrine tumors: A multi-institution observational study in Taiwan. AB - AIM: Everolimus is an inhibitor of mTOR, approved for treatment of advanced pancreatic neuroendocrine tumors (NETs). The purpose of this observational study was to evaluate the efficacy and safety of everolimus in treatment of progressive, advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in Taiwan. METHODS: Fifty-three patients with progressive, advanced GEP-NETs who received everolimus treatment between January 2008 and August 2014 were selected. Patient characteristics, tumor features, safety profiles and treatment efficacy were retrospectively analyzed. RESULTS: Mean follow-up duration was 23.7 (1.2-70) months and 37 of 53 patients (69.8%) remained alive at the end of study. The one- and two-year overall survival rates were 90.5% and 75.4%, respectively. The median progression-free survival (PFS) was 18.9 (95% confidence interval; 10.9 26.8) months. Partial response was observed in 15 (28.3%) patients, 29 (54.7%) patients had stable disease and nine (17%) patients had progressive disease. Patients with World Health Organization (WHO) grade I NETs, nonfunctional tumors and liver metastasis burden <10% had significantly better PFS with everolimus treatment. Adverse events observed were stomatitis (35.8%), hyperglycemia (22.6%) and rash (18.8%). Seven (15.4%) patients experienced severe adverse events (grade 3 or more), including hyperglycemia (4.4%), anemia (4.4%), fatigue (2.2%) and elevated liver function (2.2%). One (2.2%) patient died from grade 5 interstitial pneumonitis. CONCLUSION: Everolimus was an effective treatment for Taiwanese patients with progressive advanced GEP-NETs. Patients with nonfunctional NETs had a trend toward longer PFS, whereas patients with liver metastases burden <10% had a trend toward longer overall survival time receiving everolimus treatment. PMID- 27357445 TI - FCR front-line therapy and quality of life in patients with chronic lymphocytic leukemia. AB - The chemoimmunotherapy FCR (fludarabine and cyclophosphamide with rituximab) is the standard first-line treatment for physically fit chronic lymphocytic leukemia (CLL) patients. To assess the risks and benefits, we investigated health-related quality of life (HRQOL). 817 untreated CLL patients received either FC or FCR within the GCLLSG CLL8 trial. The European Organization for Research and Treatment of Cancer Quality of life Questionnaire C30 was sent to all patients at baseline, after 3, 6, and 12 months and then yearly as follow-up. A total of 769 (94%) of 817 patients completed at least one questionnaire. Comparing HRQOL of CLL patients with the general German population, CLL patients' health declined in most scales except for global health and pain. No major differences in HRQOL were found during treatment or follow-up between both treatment arms. Females were more likely to have treatment-related symptoms than males. Although FCR was associated with more side effects, this did not influence HRQOL. During follow-up after FCR only minor improvement of HRQOL compared with FC was assessed. PMID- 27357446 TI - Intensity and prevalence of depressive states in cancer inpatients: a large sample descriptive study. AB - In cancer patients, depression causes suffering during the whole disease trajectory and it also influences the personal perception of well-being as well as treatment adherence. Consequently, its better definition is needed for planning more tailored supportive programmes. This study was aimed to provide information on depressive state intensity and prevalence in an heterogeneous sample of cancer inpatients. In addition, associations were studied between depressive state and different socio-demographic and clinical factors. A total of 1,147 consecutive adult cancer inpatients completed the Center for Epidemiologic Studies Scale on Depression together with a form for collecting socio-demographic and clinical data. The mean score of depression was 16.9 (SD = 9.3). There were differences in depression intensity associated with gender (p < .001), age (p = .001) and cancer type (p < .001), but not with education level (p = .282) or marital status (p = .436). Of the entire sample 13.9% had depressive states; this percentage raised to 26.2% if a less stringent criterion was used. These data reinforce the importance of a clinical and research focus on depression in oncology. As differences according to gender, age and diagnosis exist in depression prevalence and intensity, tailored supportive intervention should be planned and verified for effectiveness and efficacy. PMID- 27357444 TI - Notch-independent RBPJ controls angiogenesis in the adult heart. AB - Increasing angiogenesis has long been considered a therapeutic target for improving heart function after injury such as acute myocardial infarction. However, gene, protein and cell therapies to increase microvascularization have not been successful, most likely because the studies failed to achieve regulated and concerted expression of pro-angiogenic and angiostatic factors needed to produce functional microvasculature. Here, we report that the transcription factor RBPJ is a homoeostatic repressor of multiple pro-angiogenic and angiostatic factor genes in cardiomyocytes. RBPJ controls angiogenic factor gene expression independently of Notch by antagonizing the activity of hypoxia inducible factors (HIFs). In contrast to previous strategies, the cardiomyocyte specific deletion of Rbpj increased microvascularization of the heart without adversely affecting cardiac structure or function even into old age. Furthermore, the loss of RBPJ in cardiomyocytes increased hypoxia tolerance, improved heart function and decreased pathological remodelling after myocardial infarction, suggesting that inhibiting RBPJ might be therapeutic for ischaemic injury. PMID- 27357448 TI - Remarkable magnetostructural coupling around the magnetic transition in CeCo0.85Fe0.15Si. AB - We report a detailed study of the magnetic properties of CeCo0.85Fe0.15Si under high magnetic fields (up to 16 Tesla) measuring different physical properties such as specific heat, magnetization, electrical resistivity, thermal expansion and magnetostriction. CeCo0.85Fe0.15Si becomes antiferromagnetic at [Formula: see text] K. However, a broad tail (onset at [Formula: see text] K) in the specific heat precedes that second order transition. This tail is also observed in the temperature derivative of the resistivity. However, it is particularly noticeable in the thermal expansion coefficient where it takes the form of a large bump centered at T X . A high magnetic field practically washes out that tail in the resistivity. But surprisingly, the bump in the thermal expansion coefficient becomes a well pronounced peak fully split from the magnetic transition at T N . Concurrently, the magnetoresistance also switches from negative to positive above T N . The magnetostriction is considerable and irreversible at low temperature ([Formula: see text] at 2 K) when the magnetic interactions dominate. A broad jump in the field dependence of the magnetostriction observed at low T may be the signature of a weak ongoing metamagnetic transition. Taking altogether the results indicate the importance of the lattice effects on the development of the magnetic order in these alloys. PMID- 27357447 TI - Developmental transcription factor NFIB is a putative target of oncofetal miRNAs and is associated with tumour aggressiveness in lung adenocarcinoma. AB - Genes involved in fetal lung development are thought to play crucial roles in the malignant transformation of adult lung cells. Consequently, the study of lung tumour biology in the context of lung development has the potential to reveal key developmentally relevant genes that play critical roles in lung cancer initiation/progression. Here, we describe for the first time a comprehensive characterization of miRNA expression in human fetal lung tissue, with subsequent identification of 37 miRNAs in non-small cell lung cancer (NSCLC) that recapitulate their fetal expression patterns. Nuclear factor I/B (NFIB), a transcription factor essential for lung development, was identified as a potential frequent target for these 'oncofetal' miRNAs. Concordantly, analysis of NFIB expression in multiple NSCLC independent cohorts revealed its recurrent underexpression (in ~40-70% of tumours). Interrogation of NFIB copy number, methylation, and mutation status revealed that DNA level disruption of this gene is rare, and further supports the notion that oncofetal miRNAs are likely the primary mechanism responsible for NFIB underexpression in NSCLC. Reflecting its functional role in regulating lung differentiation, low expression of NFIB was significantly associated with biologically more aggressive subtypes and, ultimately, poorer survival in lung adenocarcinoma patients. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 27357449 TI - Time resolved X-ray Dark-Field Tomography Revealing Water Transport in a Fresh Cement Sample. AB - Grating-based X-ray dark-field tomography is a promising technique for biomedical and materials research. Even if the resolution of conventional X-ray tomography does not suffice to resolve relevant structures, the dark-field signal provides valuable information about the sub-pixel microstructural properties of the sample. Here, we report on the potential of X-ray dark-field imaging to be used for time-resolved three-dimensional studies. By repeating consecutive tomography scans on a fresh cement sample, we were able to study the hardening dynamics of the cement paste in three dimensions over time. The hardening of the cement was accompanied by a strong decrease in the dark-field signal pointing to microstructural changes within the cement paste. Furthermore our results hint at the transport of water from certain limestone grains, which were embedded in the sample, to the cement paste during the process of hardening. This is indicated by an increasing scattering signal which was observed for two of the six tested limestone grains. Electron microscopy images revealed a distinct porous structure only for those two grains which supports the following interpretation of our results. When the water filled pores of the limestone grains empty during the experiment the scattering signal of the grains increases. PMID- 27357450 TI - [Delusional depression : Diagnostics, phenomenology and therapy]. AB - Depressive delusion is the key symptom of psychotic depression also known as major depressive disorder with psychotic features (ICD-10: F 32.3). Delusional topics are limited to guilt, impoverishment and hypochondria. Kurt Schneider described these as being the three primordial fears of human beings. Psychotic depression is distinguished by the particular severity and frequency of the episodes of illness as well as by increased suicidal tendencies. Although one in five patients with a major depression experiences psychotic symptoms, this condition is all too easily overlooked and the appropriate therapy is not initiated. Here we use case histories to illustrate some of the obstacles to diagnosis arising from the difficulty of identifying delusions hidden in a person's experience of depression, life history and personality. A targeted active exploration of these difficulties is significant taking into account the observable symptoms and not only the subjectively experienced symptoms. A phenomenological approach is chosen to explore the matter of depressive delusion and to investigate the interaction of delusion and affect and the special importance of anxiety for the genesis of delusion. In accordance with the current treatment recommendations and against this background, it is proposed that the pharmacological strategy should be supplemented by the use of benzodiazepines more often than has it has been in the past. PMID- 27357451 TI - [Specific questions in the focus of the evaluation]. PMID- 27357452 TI - [Erratum to: Suicide and euthanasia. Discourse on physician-assisted suicide]. PMID- 27357453 TI - [Invasive neurology in focus]. PMID- 27357454 TI - [Provision of outpatient specialist care for mental disorders : Minor regional differences in treatment needs, major regional differences in availability]. AB - BACKGROUND: Due to the high burden attributed to mental disorders, an important purpose of a general healthcare system is to provide comprehensive medical specialist care that is both locally available and in line with demand; however, the density of outpatient physicians and psychotherapists significantly varies between regions in Germany. To verify if these variations reflect regional variations of morbidity rates, routine data of statutory health insurance companies are analyzed on a regular basis. But these administrative data directly depend on the actual regional health care supply. Hence, independent epidemiological data on prevalence rates of mental disorders could be a valuable supplement. METHODS: Analyses are based on prevalence rates of the representative epidemiological German health interview and examination survey and its mental health module (DEGS1-MH) as well as supplemental data from the German national and regional associations of statutory health insurance physicians. The associations between prevalence rates and density of outpatient physicians and psychotherapists were computed for the DEGS sample points, representing 139 different German districts. Transregional care provision for neighboring regions was taken into account. RESULTS: There were neither significant associations of regional density of outpatient physicians and psychotherapists with prevalence rates of mental disorders in general nor with prevalence rates of severe mental disorders; however, taking into account transregional care provision for neighboring regions the huge variability of provider density decreases. DISCUSSION: The regional inequality of physician and psychotherapist density cannot be explained by regional differences in treatment needs. The results indicate potential improvements in healthcare provision for mental disorders in Germany through the adaptation to actual morbidity rates; however, the definition of treatment needs in mental disorders requires further evaluation. PMID- 27357455 TI - [German neurology and neurologists during the Third Reich: brain research and "euthanasia"]. AB - The connection between systematic killing of the mentally ill and disabled, euphemistically called "euthanasia" in the National Socialism ideology, and German brain research has been thoroughly investigated and in detail; however, the impact of this criminal nexus on the image and self-perception of German neurologists as well as the status of neurology as a medical discipline is still the subject of controversial debates.Between 1939 and 1945 the Kaiser Wilhelm Institute (KWI) in Berlin along with other research centres were insofar enmeshed in the "euthanasia" program as brains of killed patients were dissected in the guise of "concomitant research" in order to generate medical knowledge. Affected were mainly individuals suffering from oligophrenia, early childhood brain atrophy, cerebral palsy and epilepsy. According to current historical research, collegial networks were instrumental in receiving brains of killed patients. Furthermore, civil research units were supplemented by military ones at the KWI. These, too, were concerned with the collection of medical knowledge, for instance on injuries of the brain and spinal cord. The historical approach to consider the Nazi organizations and medicine as "resources for each other" seems, therefore, at least in part applicable to neurology. PMID- 27357456 TI - [Invasive stroke treatment - Study results and clinical routine : Lost in translation?]. AB - OBJECTIVE: How can the overwhelmingly positive results of the five randomized thrombectomy trials published in 2015 be transferred to the clinical routine? MATERIAL AND METHODS: Analysis of trial-specific characteristics with regard to implementation of mechanical thrombectomy into clinical routine. RESULTS: Stroke patients with symptomatic proximal artery occlusion are principally eligible for mechanical thrombectomy; however, the stroke patients included in the thrombectomy trials are not representative of all stroke patients. They were carefully selected according to clinical and imaging criteria as well as to the time window from symptom onset. Furthermore, they were treated in highly selected specialized stroke centers. Analysis of the five trials and the Catalan population-based SONIIA registry revealed that the observed number needed to treat (NNT) of 5 to reach a modified Rankin scale (mRS) score of 0-2 only applies to approximately 1 % of all stroke patients. The NNT for the remaining patients who are principally eligible for thrombectomy requires further study. Currently, centralization seems to be useful to facilitate mechanical thrombectomy in routine care leading to several problems that have to be dealt with in particular regions. Secondary transport to thrombectomy centers plays a major role in this context and has to be provided with highest priority. CONCLUSION: Only careful analysis of study results and the background circumstances will enable adequate organization and successful practical implementation of this highly effective therapy in the clinical routine. Regional conditions have to be considered and will be crucial in this context. PMID- 27357457 TI - [Fredy Quadfasel (1902-1981) : Neuropsychiatrist, politically persecuted NS opponent and his impact in American exile]. AB - The physician and psychologist Dr. Fredy Quadfasel, born in East Prussia, was trained in neuropsychiatry by Kurt Goldstein in Frankfurt/Main and by Karl Bonhoeffer at the Charite in Berlin. After he was detained by the Gestapo due to political opposition, he was probably denounced for offending the so-called Malicious Practices Act (Heimtuckegesetz) from March 1933, and imprisoned for 2-3 months. In 1934/35 he emigrated to the USA via England and Canada, where he initially ran a neuropsychiatry office in New York. Very soon he was able to take on an academic post and became an instructor in neurology. After medical military service in 1944-1947 at the Cushing General Hospital in Framingham near Boston, he was appointed head of the neurological department. Later he moved on to the Boston Veterans Administration Hospital. His academic positions included being an instructor in neurology at Harvard Medical School and associate professor at the Boston University School of Medicine. He had a considerable impact on neurology, especially on the locally emerging discipline of neuropsychology represented by Harold Goodglass and Norman Geschwind. Despite a lack of personal records of Quadfasel, a chequered reconstruction of his life and work was possible due to many archival documents with which it was possible to trace the career of a highly esteemed neurologist in Germany and the USA. PMID- 27357458 TI - [Potential errors in vascular patients due to anatomical variants of the ascending pharyngeal artery]. PMID- 27357459 TI - Biomarker-Driven Treatments Yield Better Results. AB - According to a meta-analysis of 351 phase I trials, choosing a therapy based on the abnormalities that drive a tumor yields higher response rates than therapeutic selections that aren't biomarker-driven. PMID- 27357460 TI - Isolated tuberculosis of right internal mammary lymph node presented like right breast abscess with mammary fistula. PMID- 27357461 TI - A Multidisciplinary Patient Navigation Program Improves Compliance With Adjuvant Breast Cancer Therapy in a Public Hospital. AB - Cancer health disparities affecting low-income and minority patients have been well documented to lead to poor outcomes. This report examines the impact of patient navigation on adherence to prescribed adjuvant breast cancer treatment. A multidisciplinary patient navigation program was initiated at a public safety net hospital to improve compliance with 3 National Quality Forum measures: (1) administration of combination chemotherapy for women with Stage (defined by the American Joint Committee on Cancer [AJCC]) T1c, II, or III hormone receptor negative breast cancer within 120 days; (2) administration of endocrine therapy for women with AJCC Stage T1c, II, or III hormone receptor-positive breast cancer within 365 days; and (3) radiation therapy for women receiving breast-conserving surgery within one year. Implementation of a multidisciplinary patient navigation program reduced time to treatment and improved compliance with adjuvant therapy for breast cancer in an underserved minority community. PMID- 27357462 TI - Effectively Reducing CK-MB Utilization Using Computer Order Entry in the Emergency Department. PMID- 27357463 TI - A Computerized Provider Order Entry-Based Alerting System Advising Appropriate Drug Dosage for Patients With Renal Insufficiency. PMID- 27357464 TI - Examining social support, rumination, and optimism in relation to binge eating among Caucasian and African-American college women. AB - PURPOSE: Binge eating is a significant concern among college age women-both Caucasian and African-American women. Research has shown that social support, coping, and optimism are associated with engaging in fewer negative health behaviors including binge eating among college students. However, the impact of sources of social support (i.e., support from family, friends, and a special person), rumination, and optimism on binge eating as a function of race/ethnicity has received less attention. The purpose of this study was to examine the association between social support, rumination, and optimism and binge eating among Caucasian and American-American women, separately. METHOD: Caucasian (n = 100) and African-American (n = 84) women from a university in the Mid-Atlantic US completed an online survey about eating behaviors and psychosocial health. RESULTS: Social support from friends was associated with less likelihood of binge eating among Caucasian women. Social support from family was associated with less likelihood of binge eating among African-American women, but greater likelihood of binge eating among Caucasian women. Rumination was associated with greater likelihood of binge eating among Caucasian and African-American women. Optimism was associated with less likelihood of binge eating among African-American women. CONCLUSIONS: These results demonstrate similarities and differences in correlates of binge eating as a function of race/ethnicity. PMID- 27357465 TI - Functional identification of two minor capsid proteins from Chinese wheat mosaic virus using its infectious full-length cDNA clones. AB - Full-length cDNA clones of Chinese wheat mosaic virus (CWMV) RNA1 and RNA2 were produced from single reverse transcription PCR reactions and transcripts were shown to be infectious in both wheat and Nicotiana benthamiana. An efficient and reliable agro-infiltration method was then developed for reverse genetic assays in N. benthamiana. Inoculation of infectious cDNA clones resulted in obvious chlorotic symptoms, and CWMV viral genomic RNAs, capsid protein (CP)-related proteins, and typical rod-shaped particles were detectable on the inoculated and upper leaves, similar to those of WT virus. The optimal temperature for virus multiplication was 12 degrees C, but the optimum for systematic infection in plants was 17 degrees C. Mutant clones that abolished the N- or C-terminal extensions of the major CP did not inhibit systemic infection or the formation of rod-shaped particles but sometimes modified the symptoms in inoculated plants. These results suggest that the two minor CP-related proteins of CWMV are dispensable for viral infection, replication, systemic movement and virion assembly in plants. PMID- 27357466 TI - Rare cause of central cyanosis: right pulmonary artery to left atrial fistula. AB - A fistula between the right pulmonary artery and the left atrium is a very rare cause of central cyanosis. A clinical diagnosis is often made by first excluding other common causes and then performing diagnostic catheterization. Surgical closure offers a definitive cure for this rare congenital anomaly. PMID- 27357467 TI - Minimally invasive mitral valve repair for functional mitral regurgitation in severe heart failure: MitraClip versus minimally invasive surgical approach. AB - OBJECTIVES: To compare the outcomes of MitraClip versus minimally invasive surgical mitral valve repair in high-risk patients with significant functional mitral regurgitation (FMR) and severe heart failure in a centre having pilot versus extensive experience with the MitraClip and the minimally invasive surgical approach, respectively. METHODS: The MitraClip group consisted of 24 high-surgical-risk patients [age 75 +/- 9 years, 75% males, NYHA III/IV 88%, left ventricular (LV) ejection fraction 31 +/- 9%, EuroSCORE II 18 +/- 14%], while the surgical group consisted of 48 patients matched for age, NYHA class and LV ejection fraction. RESULTS: Patients undergoing MitraClip versus those undergoing surgical repair showed higher prevalence of ischaemic LV dysfunction and larger LV end-diastolic diameter (both P < 0.05). Both the MitraClip and the surgical repair groups had similar 30-day mortality rates (4 vs 13%, P = 0.41) and prevalence of serious adverse events (25 vs 38%, P = 0.43). The median follow-up was 1028 days (IQR: 272-1564 days) in the MitraClip group and 890 days (IQR: 436 1381 days) in the surgical group (P = 0.95). Total all-cause mortality (54 vs 60%, log-rank P = 0.64) and rates of rehospitalizations for heart failure (42 vs 29%, log-rank P = 0.68) did not differ significantly between groups. Both techniques were associated with significant decrease in NYHA class and severity of FMR (P < 0.001 for all) and with a similar degree of stabilization of LV remodelling (P = NS). CONCLUSION: Despite the significant baseline differences in accumulated expertise and risk profile between the surgical and the MitraClip groups, both minimally invasive techniques were associated with similar 30-day and long-term outcomes. PMID- 27357468 TI - Circulating histones for predicting prognosis after cardiac surgery: a prospective study. AB - OBJECTIVES: The objective of this study was to assess the perioperative changes in circulating histones and their relationships with other biomarkers and clinical outcomes after cardiac surgery with cardiopulmonary bypass (CPB) in patients. METHODS: Forty-eight patients with congenital cardiac diseases undergoing corrective procedure with CPB were prospectively enrolled in this study. Circulating histones, N-terminal pro-brain natriuretic peptide (NT proBNP), procalcitonin (PCT) and C-reactive protein (CRP) were measured preoperatively (T0) and at 0 (T1), 24 (T2), 48 (T3) and 72 (T4) h postoperatively. The relationships between biomarkers and clinical outcomes were analysed. RESULTS: Circulating histones, NT-proBNP, PCT and CRP increased significantly postoperatively, with histones reaching the peak value earliest at T1. Circulating histone levels were higher in patients with adverse events. Receiver operating characteristic curve analysis showed that peak histone levels had a better predictive value for adverse events postoperatively. Peak histone levels correlated with the peak level of NT-proBNP (r = 0.563, P < 0.01), PCT (r = 0.551, P < 0.01), CRP (r = 0.606, P < 0.01) and clinical parameters such as ventilation time (r = 0.601, P < 0.01) and intensive care unit time (r = 0.623, P < 0.01). CONCLUSIONS: Circulating histones reached peak levels faster than NT proBNP, PCT and CRP. Furthermore, peak histone levels correlated with biomarkers and postoperative clinical outcomes. Circulating histones may be used as a prognostic indicator for patients after cardiac surgery with CPB. CLINICAL TRIALS: ClinicalTrials.gov (ID: NCT02325765). PMID- 27357469 TI - Incidence, risk factors and prognosis of postoperative atrial arrhythmias after lung transplantation: a systematic review and meta-analysis. AB - Postoperative atrial arrhythmia is the most common dysrhythmia seen after lung transplantation. However, risk factors for postoperative atrial arrhythmias and their impact on outcomes were inconsistent. The aim of our study was to conduct a meta-analysis to analyse risk factors of postoperative atrial arrhythmias and the impact of postoperative atrial arrhythmias on outcomes after lung transplantation. All eligible articles from MEDLINE, EMBASE, CENTRAL and the Chinese BioMedical Literature Database (until November 2015) were incorporated into this study. We extracted the data from the included studies and performed a meta-analysis to evaluate predictors for postoperative atrial arrhythmias and their impact on outcomes. R software and STATA 13.0 software were used for the meta-analysis. A total of 2094 patients from 11 studies were included in this meta-analysis. The pooled incidence of postoperative atrial arrhythmias after lung transplantation was 31% [95% confidence interval (CI), 25-37%]. We found that gender (female versus male) with an odds ratio (OR) of 0.44 (95% CI 0.35 0.56, P < 0.001), age (>50 vs <=50 or atrial arrhythmias versus non-atrial arrhythmias) with OR of 2.73 (95% CI 1.86-4.00, P < 0.001) and weighted mean difference (WMD) of 5.88 years (95% CI 3.69-8.07, P < 0.001), history of atrial arrhythmias with OR of 1.76 (95% CI 1.34-2.32, P = 0.002), vasopressor use with OR of 1.76 (95% CI 1.34-2.32, P < 0.001), cystic fibrosis with OR of 0.32 (95% CI 0.18-0.59, P < 0.001), interstitial lung disease with OR of 1.85 (95% CI 1.27 2.71, P = 0.001), hypertension with OR of 1.49 (95% CI 1.12-1.97, P = 0.006), coronary artery disease with OR of 1.58 (95% CI 1.20-2.08, P = 0.001), hyperlipidaemia with OR of 1.52 (95% CI 1.06-2.20, P = 0.025) and left atrial enlargement with OR of 2.99 (95% CI 1.91-4.67, P < 0.001) were significantly associated with postoperative atrial arrhythmias after lung transplantation. Postoperative atrial arrhythmias had a significant influence on length of stay (WMD 9.72, 95% CI 5.07-14.38, P < 0.001) and overall survival (OS) (hazard ratio 1.72, 95% CI 1.39-2.12, P < 0.001) after lung transplantation. In conclusion, the significant risk factors for postoperative atrial arrhythmias were gender, age, history of atrial arrhythmias, vasopressor use, cystic fibrosis, interstitial lung disease, hypertension, coronary artery disease, hyperlipidaemia, cardiac index and left atrial size. Development of postoperative atrial arrhythmias has prognostic implications for length of stay and overall survival after lung transplantation. Prospective and randomized trials are needed to address these issues in the future. PMID- 27357470 TI - FLUID AND ION SECRETION BY MALPIGHIAN TUBULES OF LARVAL CHIRONOMIDS, Chironomus riparius: EFFECTS OF REARING SALINITY, TRANSPORT INHIBITORS, AND SEROTONIN. AB - Larvae of Chironomus riparius respond to ion-poor and brackish water (IPW, BW) conditions by activating ion uptake mechanisms in the anal papillae and reducing ion absorption at the rectum, respectively. The role that the Malpighian tubules play in ion and osmoregulation under these conditions is not known in this species. This study examines rates of fluid secretion and major cation composition of secreted fluid from tubules of C. riparius reared in IPW, freshwater (FW) and BW. Fluid secretion of tubules from FW and BW larvae was similar but tubules from IPW larvae secrete fluid at higher rates, are more sensitive to serotonin stimulation, and the secreted fluid contains less Na(+) . Therefore in IPW, tubules work in concert with anal papillae to eliminate excess water while conserving Na(+) in the hemolymph. Tubules do not appear to play a significant role in ion/osmoregulation under BW. Serotonin immunoreactivity in the nervous system and gastrointestinal tract of larval C. riparius was similar to that seen in mosquito larvae with the exception that the hindgut was devoid of staining. Hemolymph serotonin titer was similar in FW and IPW; hence, serotonin is not responsible for the observed high rates of fluid secretion in IPW. Instead, it is suggested that serotonin may work in a synergistic manner with an unidentified hormonal factor in IPW. Ion transport mechanisms in the tubules of C. riparius are pharmacologically similar to those of other insects. PMID- 27357471 TI - The stability and generation pattern of thermally formed isocyanic acid (ICA) in air - potential and limitations of proton transfer reaction-mass spectrometry (PTR-MS) for real-time workroom atmosphere measurements. AB - Isocyanic acid (ICA) in vapour phase has been reported to be of unstable nature, making the occupational hygienic relevance of ICA questionable. The stability of pure ICA in clean air at different humidity conditions was investigated by Fourier transform-infrared spectrometric (FT-IR) measurements. Furthermore, the stability of ICA in a complex atmosphere representative thermal degradation hot work procedures were examined by performing parallel measurements by proton transfer reaction-mass spectrometric (PTR-MS) instrumentation and off-line denuder air sampling using di-n-butylamine (as a derivatization agent prior to liquid chromatography mass spectrometric (LC-MS) determination). The apparent half-life of ICA in pure ICA atmospheres was 16 to 4 hours at absolute humidity (AH) in the range 4.2 to 14.6 g m(-3), respectively. In a complex atmosphere at an initial AH of 9.6 g m(-3) the apparent half-life of ICA was 8 hours, as measured with the denuder method. Thus, thermally formed ICA is to be considered as a potential occupational hazard with regard to inhalation. The generation pattern of ICA formed during controlled gradient (100-540 degrees C) thermal decomposition of different polymers in the presence of air was examined by parallel PTR-MS and denuder air sampling. According to measurement by denuder sampling ICA was the dominant aliphatic isocyanate formed during the thermal decomposition of all polymers. The real-time measurements of the decomposed polymers revealed different ICA generation patterns, with initial appearance of thermally released ICA in the temperature range 200-260 degrees C. The PTR-MS ICA measurements was however affected by mass overlap from other decomposition products at m/z 44, illustrated by a [ICA]Denuder/[ICA]PTR-MS ratio ranging from 0.04 to 0.90. These findings limits the potential use of PTR-MS for real time measurements of thermally released ICA in field, suggesting parallel sampling with short-term sequential off-line methodology. PMID- 27357472 TI - Body weight and dysautonomia in early Parkinson's disease. AB - OBJECTIVES: Patients with Parkinson's disease (PD) begin to lose weight several years before diagnosis, which suggests weight variation is associated with some factor(s) that precede the onset of motor symptoms. This study aimed to investigate the association of autonomic nervous system with body weight in patients with PD. MATERIALS AND METHODS: The subjects were 90 patients with early de novo PD. We examined the associations of body mass index (BMI) with sympathetic nervous activity reflected in orthostatic intolerance or cardiac uptake of 123 I-metaiodobenzylguanidine and parasympathetic nervous activity reflected in constipation or heart rate variability (HRV). RESULTS: Twelve patients (13.3%) were overweight (BMI>25 kg/m2 ), 62 patients (68.9%) were normal weight (18.5?BMI<25 kg/m2 ), and 16 patients (17.8%) were underweight (BMI<18.5 kg/m2 ). Underweight patients had greater disease severity and decrease in blood pressure on head-up tilt-table testing, higher cardiac washout ratio of 123 I metaiodobenzylguanidine, and lower HRV and complained of constipation more often than those with normal-weight or overweight patients. On multiple regression analyses, the correlation of these variables with BMI maintained statistical significance after adjustment for age, sex, symptom duration, and motor subtype. CONCLUSIONS: Dysautonomia and disease severity are closely related to body weight independently of age, sex, symptom duration, and motor subtype. Dysautonomia may play a partial role on weight variation in the early stage of PD. PMID- 27357473 TI - Impact of fitting dominance and additive effects on accuracy of genomic prediction of breeding values in layers. AB - Most genomic prediction studies fit only additive effects in models to estimate genomic breeding values (GEBV). However, if dominance genetic effects are an important source of variation for complex traits, accounting for them may improve the accuracy of GEBV. We investigated the effect of fitting dominance and additive effects on the accuracy of GEBV for eight egg production and quality traits in a purebred line of brown layers using pedigree or genomic information (42K single-nucleotide polymorphism (SNP) panel). Phenotypes were corrected for the effect of hatch date. Additive and dominance genetic variances were estimated using genomic-based [genomic best linear unbiased prediction (GBLUP)-REML and BayesC] and pedigree-based (PBLUP-REML) methods. Breeding values were predicted using a model that included both additive and dominance effects and a model that included only additive effects. The reference population consisted of approximately 1800 animals hatched between 2004 and 2009, while approximately 300 young animals hatched in 2010 were used for validation. Accuracy of prediction was computed as the correlation between phenotypes and estimated breeding values of the validation animals divided by the square root of the estimate of heritability in the whole population. The proportion of dominance variance to total phenotypic variance ranged from 0.03 to 0.22 with PBLUP-REML across traits, from 0 to 0.03 with GBLUP-REML and from 0.01 to 0.05 with BayesC. Accuracies of GEBV ranged from 0.28 to 0.60 across traits. Inclusion of dominance effects did not improve the accuracy of GEBV, and differences in their accuracies between genomic-based methods were small (0.01-0.05), with GBLUP-REML yielding higher prediction accuracies than BayesC for egg production, egg colour and yolk weight, while BayesC yielded higher accuracies than GBLUP-REML for the other traits. In conclusion, fitting dominance effects did not impact accuracy of genomic prediction of breeding values in this population. PMID- 27357475 TI - Self-assembly of repulsive interfacial particles via collective sinking. AB - Charged colloidal particles trapped at an air-water interface are well known to form an ordered crystal, stabilized by a long ranged repulsion; the details of this repulsion remain something of a mystery, but all experiments performed to date have confirmed a dipolar-repulsion, at least at dilute concentrations. More complex arrangements are often observed, especially at higher concentration, and these seem to be incompatible with a purely repulsive potential. In addition to electrostatic repulsion, interfacial particles may also interact via deformation of the surface: so-called capillary effects. Pair-wise capillary interactions are well understood, and are known to be too small (for these colloidal particles) to overcome thermal effects. Here we show that collective effects may significantly modify the simple pair-wise interactions and become important at higher density, though we remain well below close packing throughout. In particular, we show that the interaction of many interfacial particles can cause much larger interfacial deformations than do isolated particles, and show that the energy of interaction per particle due to this "collective sinking" grows as the number of interacting particles grows. Though some of the parameters in our simple model are unknown, the scaling behaviour is entirely consistent with experimental data, strongly indicating that estimating interaction energy based solely on pair-wise potentials may be too simplistic for surface particle layers. PMID- 27357476 TI - Skin Regeneration Symposium Cambridge, 12-13 April 2016. AB - The Annual Skin Regeneration Symposium, held in Cambridge, UK, 12-13 April 2016, explored the latest advancements in skin repair, regeneration and restoration, and the impact this has on patients. With over 140 delegates from the disciplines of burn and trauma care, chronic wounds and esthetic medicine, the symposium sparked lively debate and the sharing of results from interesting case studies, clinical trials and basic research to support the use of a Regenerative Epithelial Suspension produced using the ReCell((r)) technology. Furthermore, it enabled delegates and speakers alike to share ideas and discuss how to improve the quality of care for patients. PMID- 27357474 TI - Phosphoproteomic analysis of Methanohalophilus portucalensis FDF1(T) identified the role of protein phosphorylation in methanogenesis and osmoregulation. AB - Methanogens have gained much attention for their metabolic product, methane, which could be an energy substitute but also contributes to the greenhouse effect. One factor that controls methane emission, reversible protein phosphorylation, is a crucial signaling switch, and phosphoproteomics has become a powerful tool for large-scale surveying. Here, we conducted the first phosphorylation-mediated regulation study in halophilic Methanohalophilus portucalensis FDF1(T), a model strain for studying stress response mechanisms in osmoadaptation. A shotgun approach and MS-based analysis identified 149 unique phosphoproteins. Among them, 26% participated in methanogenesis and osmolytes biosynthesis pathways. Of note, we uncovered that protein phosphorylation might be a crucial factor to modulate the pyrrolysine (Pyl) incorporation and Pyl mediated methylotrophic methanogenesis. Furthermore, heterologous expression of glycine sarcosine N-methyltransferase (GSMT) mutant derivatives in the osmosensitive Escherichia coli MKH13 revealed that the nonphosphorylated T68A mutant resulted in increased salt tolerance. In contrast, mimic phosphorylated mutant T68D proved defective in both enzymatic activity and salinity tolerance for growth. Our study provides new insights into phosphorylation modification as a crucial role of both methanogenesis and osmoadaptation in methanoarchaea, promoting biogas production or reducing future methane emission in response to global warming and climate change. PMID- 27357478 TI - Solution-Stable Colloidal Gold Nanoparticles via Surfactant-Free, Hyperbranched Polyglycerol-b-polystyrene Unimolecular Templates. AB - Hyperbranched polyglycerol-block-polystyrene copolymers, denoted HPG-b-PS, are synthesized and employed as a new and effective unimolecular template for synthesizing colloidal gold (Au) nanoparticles. The coordination of noble metal precursors with polyether within the inner HPG core and subsequent in situ reduction enables the formation of well-dispersed and stable PS-capped Au nanoparticles. The inner HPG core is produced via ring opening multibranching polymerization (ROMBP) and subsequently converted into atom transfer radical polymerization (ATRP) macroinitiators for the controlled growth of polystyrene (PS) arms possessing low polydispersity (PDI < 1.31). An initial investigation into the templating parameters of HPG-b-PS was undertaken by producing templates with different arm numbers (98 and 117) and different PS chain lengths (i.e., molecular weight = 3500-13400 g/mol). It was found that the PS chain length and solvent conditions affect the quality of the resulting PS-capped colloidal Au nanoparticles. This work demonstrates, for the first time, a simple, lower-cost approach for templating nonpolar solvent-soluble PS-capped Au nanoparticles on the order of 10-30 nm in diameter. PMID- 27357477 TI - Signaling mechanism for modulation by ATP of glycine receptors on rat retinal ganglion cells. AB - ATP modulates voltage- and ligand-gated channels in the CNS via the activation of ionotropic P2X and metabotropic P2Y receptors. While P2Y receptors are expressed in retinal neurons, the function of these receptors in the retina is largely unknown. Using whole-cell patch-clamp techniques in rat retinal slice preparations, we demonstrated that ATP suppressed glycine receptor-mediated currents of OFF type ganglion cells (OFF-GCs) dose-dependently, and the effect was in part mediated by P2Y1 and P2Y11, but not by P2X. The ATP effect was abolished by intracellular dialysis of a Gq/11 protein inhibitor and phosphatidylinositol (PI)-phospholipase C (PLC) inhibitor, but not phosphatidylcholine (PC)-PLC inhibitor. The ATP effect was accompanied by an increase in [Ca(2+)]i through the IP3-sensitive pathway and was blocked by intracellular Ca(2+)-free solution. Furthermore, the ATP effect was eliminated in the presence of PKC inhibitors. Neither PKA nor PKG system was involved. These results suggest that the ATP-induced suppression may be mediated by a distinct Gq/11/PI-PLC/IP3/Ca(2+)/PKC signaling pathway, following the activation of P2Y1,11 and other P2Y subtypes. Consistently, ATP suppressed glycine receptor mediated light-evoked inhibitory postsynaptic currents of OFF-GCs. These results suggest that ATP may modify the ON-to-OFF crossover inhibition, thus changing action potential patterns of OFF-GCs. PMID- 27357479 TI - Multimorbidity, P4 medicine and holism. AB - RATIONALE, AIMS AND OBJECTIVES: Multimorbidity is a serious challenge to providing patients with quality health care. Sturmberg et al. propose a P4 or whole-person medical model based on a holistic approach to deliver such care. The aim of this commentary is to examine critically their P4 model and holistic approach. METHODS: The P4 model and holistic approach of Sturmberg et al. are analysed conceptually in terms of an effective strategy or sequence for framing P4 medicine and with respect to different philosophical notions of holism for grounding it. RESULTS: Instead of a P4 medicine strategy or sequence that emphasizes the predictive and preventive aspects of health care from a biomedical perspective, as Sturmberg et al. do, a more effective strategy or sequence for framing P4 medicine to deliver quality health care is to accentuate the personalized and participatory aspects from a humanistic perspective. The basis of this proposed strategy for P4 medicine is not a technoscientific holism that emphasizes mechanisms to define the whole utilizing bottom-up causation, as Sturmberg et al. ground their biomedical P4 model, but rather a phenomenological holism that also incorporates the person's illness experience and top-down causation. CONCLUSIONS: The proposal of Sturmberg et al. to treat patient multimorbidity through P4 medicine and a holistic approach is certainly a move in the right direction. However, to achieve their goal requires an alternative strategy for P4 medicine and a more robust notion of holism. PMID- 27357480 TI - High Frequency Dielectric Characteristics of Electrochromic, WO3 and NiO Films with LiNbO3 Electrolyte. AB - A great deal of attention has been recently focused on Electrochromic (EC) materials and EC based devices, promoting mainly applications related to display technology. In this case, EC based displays are usually actuated by the application of low dc bias voltages, changing their appearance from transparent to opaque. A variety of studies related to the optical characteristics of EC materials have been reported, however, no serious studies so far have been reported on the possible high frequency tunability of the dielectric characteristics of these materials, with the exception of the work by Rose, which presented the operation of a microwave shutter based on conductive polymers operating in the X-band. Here we report tuneable high frequency dielectric characteristics of an Electrochromic (EC) cell with a complimentary structure of Conductor/WO3/LiNbO3/NiO/Conductor in the frequency range from 1 GHz to 20 GHz. The EC cell was prepared using standard semiconductor processing technology, such as lithography, etch and deposition techniques. Our measured results indicate that tunability of high frequency dielectric characteristics as a function of dc bias voltage is achieved, and that a possibility exists for this tunability to be tailored. PMID- 27357481 TI - Non-human primate chimeras make a move. PMID- 27357482 TI - Natural water as the test medium for Ag and CuO nanoparticle hazard evaluation: An interlaboratory case study. AB - Engineered nanoparticles (NPs) have realistic potential of reaching natural waterbodies and of exerting toxicity to freshwater organisms. The toxicity may be influenced by the composition of natural waters as crucial NP properties are influenced by water constituents. To tackle this issue, a case study was set up in the framework of EU FP7 NanoValid project, performing an interlaboratory hazard evaluation of NPs in natural freshwater. Ag and CuO NPs were selected as model NPs because of their potentially high toxicity in the freshwater. Daphnia magna (OECD202) and Danio rerio embryo (OECD236) assays were used to evaluate NP toxicity in natural water, sampled from Lake Greifen and Lake Lucerne (Switzerland). Dissolution of the NPs was evaluated by ultrafiltration, ultracentrifugation and metal specific sensor bacteria. Ag NP size was stable in natural water while CuO NPs agglomerated and settled rapidly. Ag NP suspensions contained a large fraction of Ag(+) ions and CuO NP suspensions had low concentration of Cu(2+) ions. Ag NPs were very toxic (48 h EC50 1-5.5 MUg Ag/L) to D. magna as well as to D. rerio embryos (96 h EC50 8.8-61 MUg Ag/L) in both standard media and natural waters with results in good agreement between laboratories. CuO NP toxicity to D. magna differed significantly between the laboratories with 48 h EC50 0.9-11 mg Cu/L in standard media, 5.7-75 mg Cu/L in Lake Greifen and 5.5-26 mg Cu/L in Lake Lucerne. No toxicity of CuO NP to zebrafish embryos was detected up to 100 mg/L independent of the medium used. The results show that Ag and CuO NP toxicity may be higher in natural water than in the standard media due to differences in composition. NP environmental hazard evaluation can and should be carried out in natural water to obtain more realistic estimates on the toxicity. PMID- 27357483 TI - Evaluating the mobility of polymer-stabilised zero-valent iron nanoparticles and their potential to co-transport contaminants in intact soil cores. AB - The use of zero-valent iron nanoparticles (nZVI) has been advocated for the remediation of both soils and groundwater. A key parameter affecting nZVI remediation efficacy is the mobility of the particles as this influences the reaction zone where remediation can occur. However, by engineering nZVI particles with increased stability and mobility we may also inadvertently facilitate nZVI mediated contaminant transport away from the zone of treatment. Previous nZVI mobility studies have often been limited to model systems as the presence of background Fe makes detection and tracking of nZVI in real systems difficult. We overcame this problem by synthesising Fe-59 radiolabelled nZVI. This enabled us to detect and quantify the leaching of nZVI-derived Fe-59 in intact soil cores, including a soil contaminated by Chromated-Copper-Arsenate. Mobility of a commercially available nZVI was also tested. The results showed limited mobility of both nanomaterials; <1% of the injected mass was eluted from the columns and most of the radiolabelled nZVI remained in the surface soil layers (the primary treatment zone in this contaminated soil). Nevertheless, the observed breakthrough of contaminants and nZVI occurred simultaneously, indicating that although the quantity transported was low in this case, nZVI does have the potential to co-transport contaminants. These results show that direct injection of nZVI into the surface layers of contaminated soils may be a viable remediation option for soils such as this one, in which the mobility of nZVI below the injection/remediation zone was very limited. This Fe-59 experimental approach can be further extended to test nZVI transport in a wider range of contaminated soil types and textures and using different application methods and rates. The resulting database could then be used to develop and validate modelling of nZVI facilitated contaminant transport on an individual soil basis suitable for site specific risk assessment prior to nZVI remediation. PMID- 27357484 TI - Fifteen-year study of environmental dredging effect on variation of nitrogen and phosphorus exchange across the sediment-water interface of an urban lake. AB - Environmental dredging has been applied widely in Chinese lakes to reduce their internal nutrient loads. However, the efficacy of dredging to reduce internal loading of nitrogen (N) and phosphorus (P) and to improve water quality has been questioned by some researchers. In this study, the long-term (~15 years) effects of dredging to reduce internal N and P loading in a closed, polluted urban lake were investigated. The results showed that the release of soluble reactive phosphorus (SRP) could be suppressed quickly after dredging, and that the dredging effect was sustained for about 18 months. A significant release of NH4+ N was discovered during the first 2-8 months after dredging, followed by maintenance of low-level release rates for about 21-32 months. The continuous inflowing of external pollution loading led to the increase in the release rates of SRP and NH4+-N. The external pollution loading was therefore reduced three years after dredging to strengthen the remediation effect. After that, high diffusive flux from the sediment was observed for both NH4+-N and SRP during summer seasons for about six years, followed by a decreasing trend. The NH4+-N concentration in the overlying water was reduced after the reduction of external loading, while a high concentration of SRP in the overlying water was still observed during summer seasons. In conclusion, the mid-term (<3 years) reduction of internal N and P loading could be achieved by dredging if the external pollution loading were not reduced. Achieving long-term control would require modification of external loading. PMID- 27357485 TI - Caddisflies Hydropsyche spp. as biomonitors of trace metal bioavailability thresholds causing disturbance in freshwater stream benthic communities. AB - Demonstration of an ecotoxicological effect of raised toxic metal bioavailabilities on benthic macroinvertebrate communities in contaminated freshwater streams typically requires the labour-intensive identification and quantification of such communities before the application of multivariate statistical analysis. A simpler approach is the use of accumulated trace metal concentrations in a metal-resistant biomonitor to define thresholds that indicate the presence of raised trace metal bioavailabilities causing ecotoxicological responses in populations of more metal-sensitive members of the community. We explore further the hypothesis that concentrations of toxic metals in larvae of species of the caddisfly genus Hydropsyche can be used to predict metal-driven ecotoxicological responses in more metal-sensitive mayflies, especially ephemerellid and heptageniid mayflies, in metal-contaminated rivers. Comparative investigation of two caddisflies, Hydropsyche siltalai and Hydropsyche angustipennis, from metal-contaminated rivers in Cornwall and Upper Silesia, Poland respectively, has provided preliminary evidence that this hypothesis is applicable across caddisfly species and contaminated river systems. Use of a combined toxic unit approach, relying on independent data sets, suggested that copper and probably also arsenic are the drivers of mayfly ecotoxicity in the River Hayle and the Red River in Cornwall, while cadmium, lead and zinc are the toxic agents in the Biala Przemsza River in Poland. This approach has great potential as a simple tool to detect the more subtle effects of mixed trace metal contamination in freshwater systems. An informed choice of suitable biomonitor extends the principle to different freshwater habitats over different ranges of severity of trace metal contamination. PMID- 27357486 TI - Dicationic polymeric ionic-liquid-based magnetic material as an adsorbent for the magnetic solid-phase extraction of organophosphate pesticides and polycyclic aromatic hydrocarbons. AB - Magnetic particles modified with a dicationic polymeric ionic liquid are described as a new adsorbent in magnetic solid-phase extraction. They were obtained through the copolymerization of a 1,8-di(3-vinylimidazolium)octane-based ionic liquid with vinyl-modified SiO2 @Fe3 O4 , and were characterized by FTIR spectroscopy, X-ray diffraction, and vibrating sample magnetometry. The modified magnetic particles are effective in the extraction of organophosphate pesticides and polycyclic aromatic hydrocarbons. Also, they can provide different extraction performance for the selected analytes including fenitrothion, parathion, fenthion, phoxim, phenanthrene, and fluoranthene, where the extraction efficiency is found to be in agreement with the hydrophobicity of analytes. Various factors influencing the extraction efficiency, such as, the amount of adsorbent, extraction, and desorption time, and type and volume of the desorption solvent, were optimized. Under the optimized conditions, a good linearity ranging from 1 100 MUg/L is obtained for all analytes, except for parathion (2-200 MUg/L), where the correlation coefficients varied from 0.9960 to 0.9998. The limits of detection are 0.2-0.8 MUg/L, and intraday and interday relative standard deviations are 1.7-7.4% (n = 5) and 3.8-8.0% (n = 3), respectively. The magnetic solid-phase extraction combined with high-performance liquid chromatography can be applied for the detection of trace targets in real water samples with satisfactory relative recoveries and relative standard deviations. PMID- 27357487 TI - The mutational hazard hypothesis of organelle genome evolution: 10 years on. AB - Why is there such a large variation in size and noncoding DNA content among organelle genomes? One explanation is that this genomic variation results from differences in the rates of organelle mutation and random genetic drift, as opposed to being the direct product of natural selection. Along these lines, the mutational hazard hypothesis (MHH) holds that 'excess' DNA is a mutational liability (because it increases the potential for harmful mutations) and, thus, has a greater tendency to accumulate in an organelle system with a low mutation rate as opposed to one with a high rate of mutation. Various studies have explored this hypothesis and, more generally, the relationship between organelle genome architecture and the mode and efficiency of organelle DNA repair. Although some of these investigations are in agreement with the MHH, others have contradicted it; nevertheless, they support a central role of mutation, DNA maintenance pathways and random genetic drift in fashioning organelle chromosomes. Arguably, one of the most important contributions of the MHH is that it has sparked crucial, widespread discussions about the importance of nonadaptive processes in genome evolution. PMID- 27357488 TI - Therapeutic potential and critical analysis of trastuzumab and bevacizumab in combination with different chemotherapeutic agents against metastatic breast/colorectal cancer affecting various endpoints. AB - Researchers are working day and night across the globe to eradicate or at least lessen the menace of cancer faced by the mankind. The two very frequently occurring cancers faced by the human beings are metastatic breast cancer and metastatic colorectal cancer. The various chemotherapeutic agents like anthracycline, cyclophosphamide, paclitaxel, irinotecan, fluorouracil and leucovorin etc., have been used impressively for long. But the obstinate character of metastatic breast cancer and metastatic colorectal cancer needs more to tackle the threat. So, the scientists found the use of monoclonal antibodies trastuzumab (Herceptin((r))) and bevacizumab (Avastin((r))) for the same. The current study critically investigates the therapeutic potential of trastuzumab and bevacizumab in combination with various chemotherapeutic agents against metastatic breast cancer and metastatic colorectal cancer. To the best of our knowledge, this is the very first critical analysis showing percent wise increase in various positive endpoints like median time to disease progression, median survival, and progression free survival etc. for the treatment of metastatic breast/colorectal cancer using trastuzumab and bevacizumab in combination with different chemotherapeutic agents and provides the rational for the success and failure of the selected monoclonal antibodies. PMID- 27357489 TI - Current status of auxiliary partial orthotopic liver transplantation for acute liver failure. AB - Auxiliary partial orthotopic liver transplantation (APOLT) is a technique of liver transplantation (LT) where a partial liver graft is implanted in an orthotopic position after leaving behind a part of the native liver. APOLT was previously considered technically challenging with results inferior to orthotopic liver transplantation. Results of this procedure have continued to improve with improving surgical techniques and a better understanding of the natural history of acute liver failure (ALF) and liver regeneration. The procedure is being increasingly accepted as a valid treatment option for ALF-especially in children. This article reviews the historical background to this operation, advances in the technique, and its current place in the management of ALF. Liver Transplantation 22 1265-1274 2016 AASLD. PMID- 27357490 TI - A self-sustaining atomic magnetometer with tau(-1) averaging property. AB - Quantum measurement using coherent superposition of intrinsic atomic states has the advantage of being absolute measurement and can form metrological standards. One example is the absolute measurement of magnetic field by monitoring the Larmor precession of atomic spins whilst another being the Ramsey type atomic clock. Yet, in almost all coherent quantum measurement, the precision is limited by the coherence time beyond which, the uncertainty decreases only as tau(-1/2). Here we show that by non-destructively measuring the phase of the Larmor precession and regenerating the coherence via optical pumping, the self sustaining Larmor precession signal can persist indefinitely. Consequently, the precision of the magnetometer increases with time following a much faster tau(-1) rule. A mean sensitivity of 240 from 1 Hz to 10 Hz is realized, being close to the shot noise level. This method of coherence regeneration may also find important applications in improving the performance of atomic clocks. PMID- 27357491 TI - Subtle-discrete aortic dissection without bulging of the aortic wall. A rare but lethal lesion. AB - We report a subtle-discrete aortic dissection, without bulging of the aortic wall or aneurysm or valve pathology or periaortic effusion, which resulted in a lethal cardiac tamponade to a 35-year-old male. PMID- 27357492 TI - Anger and sadness as adaptive emotion expression strategies in response to negative competence and warmth evaluations. AB - Previous literature suggested that anger and sadness may be necessary to restore social bonds in the face of immediate relationship threat. The present research compared the social effectiveness of expressing anger and sadness in response to a negative personal evaluation. Results indicated that target anger in response to a negative competence evaluation, and target sadness in response to a negative warmth evaluation, had the most positive effects on the evaluators' subjectively perceived persuasiveness of the targets' communication (Study 1) and on the subjectively perceived fluency of the interaction by both interaction partners (Study 2). Results are discussed in light of the social functionality of emotion expression and the importance of interpersonal emotion congruency with evaluation content. PMID- 27357493 TI - Embedding responsible conduct in learning and research into an Australian undergraduate curriculum. AB - Responsible conduct in learning and research (RCLR) was progressively introduced into the pharmacology curriculum for undergraduate science students at The University of Western Australia. In the second year of this undergraduate curriculum, a lecture introduces students to issues such as the use of animals in teaching and responsible conduct of research. Third year student groups deliver presentations on topics including scientific integrity and the use of human subjects in research. Academic and research staff attending these presentations provide feedback and participate in discussions. Students enrolled in an optional capstone Honours year complete an online course on the responsible conduct of research and participate in an interactive movie. Once RCLR became established in the curriculum, a survey of Likert-scaled and open-ended questions examined student and staff perceptions. Data were expressed as Approval (% of responses represented by Strongly Agree and Agree). RCLR was found to be relevant to the study of pharmacology (69-100% Approval), important for one's future career (62 100% Approval), and stimulated further interest in this area (32-75% Approval). Free entry comments demonstrated the value of RCLR and constructive suggestions for improvement have now been incorporated. RCLR modules were found to be a valuable addition to the pharmacology undergraduate curriculum. This approach may be used to incorporate ethics into any science undergraduate curriculum, with the use of discipline-specific topics. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):53-59, 2017. PMID- 27357494 TI - Neighbourhood variation in the price of soda relative to milk and its association with neighbourhood socio-economic status and race. AB - OBJECTIVE: Soda consumption is high in the USA, especially among minorities and individuals of lower socio-economic status (SES); this may be due to its affordable price in relation to healthier alternatives. The objective of the present study was to examine geospatial variation in price of milk and soda, and the price of milk relative to soda, by neighbourhood SES and proportion of Hispanic and black individuals. DESIGN: Retailer soda and milk prices (n 2987; Information Resources, Inc. Academic Data Set 2004-2011) were linked to census block group sociodemographic characteristics (American Community Survey 2005 2009). Linear hierarchical regression models were used to adjust for confounders. SETTING: Large chain supermarkets and superstores (n 1743) in forty-one states and 1694 block groups (USA). RESULTS: For equivalent fluid ounces, price of soda on average was 62 % lower than milk ($US 0.23 v. $US 0.63 per serving) and there was high dispersion in milk price across geographic areas. After adjustment for confounding, neighbourhoods with a higher concentration of black and Hispanic individuals tended to have lower soda prices and higher milk prices (-$US 0.001 and +$US 0.007 in price per serving, respectively, for a one quintile increase in black/Hispanic population), while soda and milk both became less expensive as SES decreased (-$US 0.002 and -$US 0.015 in serving price per one sd decrease in SES index, respectively). CONCLUSIONS: Neighbourhoods with a higher concentration of blacks and Hispanics may be at greater risk of higher soda consumption due to more affordable prices, in absolute terms and relative to the price of milk. PMID- 27357495 TI - How home HIV testing and counselling with follow-up support achieves high testing coverage and linkage to treatment and prevention: a qualitative analysis from Uganda. AB - INTRODUCTION: The successes of HIV treatment scale-up and the availability of new prevention tools have raised hopes that the epidemic can finally be controlled and ended. Reduction in HIV incidence and control of the epidemic requires high testing rates at population levels, followed by linkage to treatment or prevention. As effective linkage strategies are identified, it becomes important to understand how these strategies work. We use qualitative data from The Linkages Study, a recent community intervention trial of community-based testing with linkage interventions in sub-Saharan Africa, to show how lay counsellor home HIV testing and counselling (home HTC) with follow-up support leads to linkage to clinic-based HIV treatment and medical male circumcision services. METHODS: We conducted 99 semi-structured individual interviews with study participants and three focus groups with 16 lay counsellors in Kabwohe, Sheema District, Uganda. The participant sample included both HIV+ men and women (N=47) and HIV uncircumcised men (N=52). Interview and focus group audio-recordings were translated and transcribed. Each transcript was summarized. The summaries were analyzed inductively to identify emergent themes. Thematic concepts were grouped to develop general constructs and framing propositional statements. RESULTS: Trial participants expressed interest in linking to clinic-based services at testing, but faced obstacles that eroded their initial enthusiasm. Follow-up support by lay counsellors intervened to restore interest and inspire action. Together, home HTC and follow-up support improved morale, created a desire to reciprocate, and provided reassurance that services were trustworthy. In different ways, these functions built links to the health service system. They worked to strengthen individuals' general sense of capability, while making the idea of accessing services more manageable and familiar, thus reducing linkage barriers. CONCLUSIONS: Home HTC with follow-up support leads to linkage by building "social bridges," interpersonal connections established and developed through repeated face-to-face contact between counsellors and prospective users of HIV treatment and male circumcision services. Social bridges link communities to the service system, inspiring individuals to overcome obstacles and access care. PMID- 27357496 TI - Disturbed eating behaviors in adolescents with type 1 diabetes. How to screen for yellow flags in clinical practice? AB - BACKGROUND: Adolescents with type 1 diabetes are at an increased risk of disturbed eating behaviors (DEBs). OBJECTIVE: The aims of this study are to (i) explore the prevalence of DEBs and associated 'yellow flags', and (ii) establish concordance between adolescents-parents and adolescents-clinicians with respect to DEBs. METHODS: Adolescents (11-16 yr) and parents completed questionnaires. A stepwise approach was used to assess DEBs: only adolescents whose answers raised psychological yellow flags for DEBs completed the Diabetes Eating Problems Scale Revised and questions from the AHEAD study. Parents and clinicians shared their observations regarding possible DEBs. Kruskal-Wallis tests, post hoc Mann-Whitney U test, and chi-squared tests were utilized to examine clinical yellow flags. Cohen's kappa was used to assess concordance. RESULTS: Of 103 adolescents participated (51.5% girls), answers of 47 (46.5%) raised psychological yellow flags, indicating body and weight concerns. A total of 8% scored above cut-off for DEBs. Clinical yellow flags were elevated glycated hemoglobin A1c (p = 0.004), older age (p = 0.034), dieting frequency (p = 0.001), reduced quality of life (p = 0.007), less diabetes self-confidence (p = 0.015), worsened diabetes management (p < 0.001), and body dissatisfaction (p < 0.001). Body Mass Index (BMI) z-scores and gender were no yellow flags. Concordance between parents and adolescents was slight (k = 0.126 and 0.141), and clinicians and adolescents was fair (k = 0.332). DISCUSSION: Half of the adolescents reported body and weight concerns, less than 1 in 10 reported DEBs. Screening for yellow flags for DEBs as a part of clinical routine using a stepwise approach and early assistance is recommended to prevent onset or deterioration of DEBs. PMID- 27357498 TI - Increased CSF aquaporin-4, and interleukin-6 levels in dogs with idiopathic communicating internal hydrocephalus and a decrease after ventriculo-peritoneal shunting. AB - BACKGROUND: Studies in animal models, in which internal hydrocephalus has been induced by obstructing the cerebrospinal fluid pathways, have documented an up regulation of the concentrations of aquaporin-4 (AQP4) in the brain. In this study, the concentrations of aquaporin-1 (AQP1), AQP1, AQP4 and interleukin-6 (IL 6) were determined in the CSF of dogs with idiopathic communicating hydrocephalus before and after the reduction of intraventricular volume following ventriculo peritoneal shunt (VP-shunt) treatment. RESULTS: The concentrations of AQP4 and IL 6 were increased in the cerebrospinal fluid of dogs with hydrocephalus compared to controls. Both parameters significantly decreased after surgical treatment, accompanied by decrease of ventricular size and the clinical recovery of the dogs. AQP1 was not detectable in CSF. CONCLUSIONS: Brain AQP4 up-regulation might be a compensatory response in dogs with hydrocephalus. Future determination of AQP4 at the mRNA and protein level in brain tissue is warranted to substantiate this hypothesis. PMID- 27357497 TI - Sleep Problems in Children with Attention Deficit/Hyperactivity Disorder: Current Status of Knowledge and Appropriate Management. AB - Attention deficit hyperactivity disorder (ADHD) affects approximately 5 % of children and adolescents, and sleep problems are common in these patients. There is growing evidence informing the significant importance of sleep problems in youth with ADHD. The sleep problems in children with ADHD include specific sleep disorders and sleep disturbances due to comorbid psychiatric disorders or ADHD medications. The specific sleep disorders of ADHD children include behaviorally based insomnia, sleep-disordered breathing, and restless legs syndrome/periodic limb movement disorder. Current practices on the management of sleep problems for ADHD children are based mostly on expert consensus, whereas more evidence-based literature can be found only recently. Assessment of the sleep conditions in ADHD children before initiation of pharmacotherapy is the currently recommended guideline, and good sleep hygiene can be considered as the first-line treatment option. In addition to modifying the dose regimens, formulation, or alternative stimulants when sleep problems are encountered in ADHD children, atomoxetine, once daily guanfacine extended release, and melatonin are potential choices for ADHD children with more severe sleep problems. In this review, we aimed to provide the most updated information, preferably based on meta-analyses, systemic review, and randomized controlled trials published in the latest 3 years, in order to be clinically useful for practitioners and clinicians. PMID- 27357499 TI - Measurement of Vaginal Microbicide Adherence Using Visual Inspection as Compared to Ultra Violet Light Assessment of Returned Empty Gel Applicators. AB - Accurate and objective measurement of adherence is critical in microbicide trials. We compared two applicator tests: visual inspection of returned empty tenofovir gel applicators (VIREA) and ultraviolet light (UVL) assessment in terms of sensitivity and specificity, and for concordance. Sensitivity and specificity analysis of 24 control applicators (12 known-inserted and 12 sham-inserted) at 4 months after receipt was 75.0 and 66.7 % for VIREA and 83.3 and 91.7 % for UVL, respectively. After an additional 3 months of storage sensitivity and specificity was 100 and 58.3 % for VIREA and 100 and 66.7 % for UVL, respectively. In January 2015, 1316 empty applicators were returned as used by 115 participants enrolled at one site in a randomized controlled trial. Assessment outcomes showed 78.8 % agreement between the techniques. Methods concurred that 22.0 % of the returned empty applicators appeared unused. By UVL assessment, 40.0 % of returned empty applicators had no evidence of vaginal insertion, translating to a potential 28.0 % less product used as compared to that returned as used by women. UVL assessment may be considered a more accurate and less subjective measure of adherence as compared to VIREA. PMID- 27357500 TI - Solo emergency care by a physician assistant versus an ambulance nurse: a cross sectional document study. AB - BACKGROUND: This study compares the assessment, treatment, referral, and follow up contact with the dispatch centre of emergency patients treated by two types of solo emergency care providers in ambulance emergency medical services (EMS) in the Netherlands: the physician assistant (PA), educated in the medical domain, and the ambulance registered nurse (RN), educated in the nursing domain. The hypothesis of this study was that there is no difference in outcome of care between the patients of PAs and RNs. METHODS: In a cross-sectional document study in two EMS regions we included 991 patients, treated by two PAs (n = 493) and 23 RNs (n = 498). The inclusion period was October 2010-December 2012 for region 1 and January 2013-March 2014 for region 2. Emergency care data were drawn from predefined and free text fields in the electronic patient records. Data were analysed using descriptive statistics. We used chi (2) and Mann-Whitney U tests to analyse for differences in outcome of care. Statistical significance was assumed at a level of P <0.05. RESULTS: Patients treated by PAs and RNs were similar with respect to patient characteristics. In general, diagnostic measurements according to the national EMS standard were applied by RNs and by PAs. In line with the medical education, PAs used a medical diagnostic approach (16 %, n = 77) and a systematic physical exam of organ tract systems (31 %, n = 155). PAs and RNs provided similar interventions. Additionally, PAs consulted more often other medical specialists (33 %) than RNs (17 %) (chi (2) = 35.5, P <0.0001). PAs referred less patients to the general practitioner or emergency department (50 %) compared to RNs (73 %) (chi (2) = 52.9, P <0.0001). Patient follow up contact with the dispatch centre within 72 h after completion of the emergency care on scene showed no variation between PAs (5 %) and RNs (4 %). CONCLUSIONS: In line with their medical education, PAs seemed to operate from a more general medical perspective. They used a medical diagnostic approach, consulted more medical specialists, and referred significantly less patients to other health care professionals compared to RNs. While the patients of the PAs did not contact the dispatch centre more often afterwards. PMID- 27357501 TI - NOD2/CARD15 gene mutations in patients with gouty arthritis. AB - Nucleotide binding and oligomerization domains/caspase recruitment domain containing protein 15 (NOD2/CARD15) is a cytoplasmic molecule controlling apoptosis and inflammatory processes by recognizing some microbial components. We aimed to identify the frequencies of NOD2/CARD15 gene mutations in patients with gouty arthritis and to determine their possible correlation with the disease phenotype. The study included 93 patients with gouty arthritis and 51 healthy controls matched for age, gender, and ethnicity. The NOD2/CARD15 R702W and G908R gene mutations were explored by the polymerase chain reaction restriction fragment length polymorphism method while the 3020insC mutation was analyzed by DNA sequencing. The mean patient age was 54.2 +/- 14.2 years and mean duration of the disease was 3.1 +/- 2.9 years. The first metatarsophalangeal and finger joint involvements were detected in 72 (77.4%) and 18 (19.5%) patients, respectively. Ankle arthritis and knee arthritis were detected in 43 (46.2%) and 20 (21.5%) patients, respectively. In total, 4 (9%) heterozygous mutations were detected in the G908R and R702W genes, while no mutation was detected in the 3020insC gene. Compared to the control group, there were no significant differences in all three DNA regions (G908R, R702W, and 3020insC; p = 0.452, p = 0.583, and p = 0.350, respectively). No correlation between the NOD2/CARD15 variants and clinical or laboratory findings (p > 0.05) was found. The frequencies of the NOD2/CARD15 gene mutations in the patients were similar to healthy control group. No association between clinical or laboratory findings and the NOD2/CARD15 gene mutations was observed. PMID- 27357502 TI - High genotypic diversity among methicillin-resistant Staphylococcus pseudintermedius isolated from canine infections in Denmark. AB - BACKGROUND: Methicillin-resistant Staphylococcus pseudintermedius (MRSP) has emerged globally in companion animals in the last decade. In Europe, the multidrug-resistant sequence type (ST)71 is widespread, but recently other clones have appeared. The objective of this study was to examine genotypic diversity and antimicrobial resistance of clinical MRSP isolates obtained from dogs, including dogs sampled on multiple occasions, in Denmark over a six-year period. For that purpose a total of 46 clinical MRSP isolates obtained from 36 dogs between 2009 and 2014 were subjected to antimicrobial susceptibility testing, multilocus sequence typing (MLST) and SCCmec typing. RESULTS: Twenty-three sequence types were identified with ST71, mostly associated with SCCmec II-III, as the most common occurring in 13 dogs. Among the remaining 33 isolates, 19 belonged to clonal complex (CC)258 comprising ST258-SCCmec IV and its single- and double locus variants. These were susceptible to 4-7 of the 22 antibiotics tested, whereas CC71 isolates were susceptible to only 2-5 antibiotics. Clone-specific differences were especially pronounced for fluoroquinolones and aminoglycosides with most CC71 isolates being resistant and almost all CC258 isolates being susceptible. Sixteen of the 19 CC258 isolates had oxacillin MICs of 0.5 g/L, whereas MICs for CC71 isolates were consistently above 4 g/L. Four of five dogs representing multiple isolates had distinct STs on different sampling events. CONCLUSIONS: The overall genotypic diversity of MRSP is high in Denmark indicating multiple acquisitions of SCCmec into distinct clones, and mutational evolution, which appears to be particularly rapid for certain ancestral clones such as ST258. ST71-SCCmec II-III is the most common MRSP lineage and is typically multidrug-resistant. CC258-SCCmec IV isolates, which emerged in Denmark since 2012, display susceptibility to a wider range of antimicrobials. The isolation of distinct STs in individual dogs over time suggests repeated exposure or short-term genetic evolution of MRSP clones within patients. PMID- 27357504 TI - Evaluation of a Public Awareness Campaign to Prevent High School Dropout. AB - Many advocacy organizations devote time and resources to increasing community awareness and educating the public in an effort to gain support for their issue. One such effort, the Dropout Prevention Campaign by America's Promise Alliance, aimed to increase the visibility of the high school dropout problem and mobilize the community to take action. The objective of this paper is to evaluate the framing of the Dropout Prevention Campaign in television news media. To evaluate this campaign, television news coverage about high school dropout in 12 U.S. communities (N = 982) was examined. A content analysis of news transcripts was conducted and coded to determine the definition of the problem, the reasons for dropout and the possible solutions. Findings indicated that the high school dropout problem was most often framed (30 % of news segments) in terms of the economic and societal implications for the community. Individual student factors as well as broader societal influences were frequently discussed as possible reasons for dropout. The most commonly mentioned solutions were school-based interventions. News segments that mentioned America's Promise Alliance were more likely to frame the issue as a crisis and to use statistics to illustrate that point. Solutions that were more likely to appear in America's Promise segments promoted community and cross-sector involvement, consistent with the messages promoted by the Dropout Prevention Campaign. The findings suggest that a media content analysis can be an effective framework for analyzing a prevention campaign. PMID- 27357503 TI - Adult obese mice suffer from chronic secondary brain injury after mild TBI. AB - BACKGROUND: A traumatic brain injury (TBI) event is a devastating injury to the brain that may result in heightened inflammation, neurodegeneration, and subsequent cognitive and mood deficits. TBI victims with co-morbidities such as heart disease, diabetes, or obesity may be more vulnerable to the secondary brain injury that follows the initial insult. Compared to lean individuals, obese subjects tend to have worse clinical outcomes and higher mortality rates after trauma. METHODS: To elucidate whether obesity predisposes individuals to worse outcomes after TBI, we subjected adult lean and obese male/female mice to a mild TBI. The injury was administered using a controlled skull impact (CSI) device. Lean or obese 6-month-old C57 BL/6 mice were subjected once to a mild TBI. Additionally, at day 30 after injury, both the lean and obese mice were tested for increased anxiety using the open field test. RESULTS: At day 30 after TBI, compared to the lean mice, we found heightened microglial (MG) activation in the cerebral cortex, corpus callosum, and hypothalamus. Another compelling finding was that, compared to the non-injured obese male control mice, the obese TBI mice had a decrease in the rate of weight gain and serum corticosterone levels at day 30 after injury. Additionally, the injured obese mice displayed higher levels of anxiety as determined by a significant decrease in time spent in the non peripheral zones in the open field test. In contrast to the obese males, the obese female mice did not exhibit increases in the number of active MG in the brain, changes in weight gain/corticosterone levels, or increased anxiety at day 30 after TBI. CONCLUSIONS: The data presented here suggests that obese mice have worse outcomes compared to lean mice after mild TBI. Also, the obese males have worse outcomes than the injured female mice. This data may explain the sequela of chronic secondary brain injury in obese adults after a single mild TBI. Also, this report may help shape how the overweight/obese populations are monitored over the days and months following a TBI. PMID- 27357505 TI - mRNA expression of TLR4, TLR9 and NF-kappaB in a neonatal murine model of necrotizing enterocolitis. AB - A neonatal model of necrotizing enterocolitis (NEC) in mice was established to examine the role of Toll-like receptors (TLRs) 4 and 9, and of nuclear factor (NF)-kappaB by quantitative detection of their mRNAs in intestinal tissue during the occurrence of NEC, and thus aid in the understanding of the basic pathogenesis of NEC. A total of 50 newborn BALB/c mice (specific pathogen-free level) ranging in age from 7 to 10 days, of either gender, and weighing 4.8-5.4 g were selected and randomly divided into a control and test group, n=25 mice per group. Mice in the control group were kept in the same cage with the mother who fed them, free from any interventions. Mice in the test group were separated from their mother 48 h following birth and placed in an incubator, artificially fed with milk substitutes, and regularly treated with hypoxia and cold stimulation (100% nitrogen anoxia for 90 sec, cold stimulation at 4C for 10 min, 3 times a day for 3 days) to induce the neonatal NEC. The general state and body weight variations of the mice were recorded, the mice were sacrificed and the intestinal tissue necrosis was evaluated visually, the degree of intestinal injury was determined by histopathological staining, and the mRNA expression levels of intestinal tissue TLR4, TLR9 and NF-kappaB were quantified. Of the 25 mice in the test group, 3 died a natural death and 22 were sacrificed; their general state was worse than that of the mice in the control group, and the body weight variations among them were considerably larger. NEC was confirmed in 12 cases by visual inspection, and the average histological scores of the mice in the test group were 3.5+/-0.6, significantly higher than that in the control group (P<0.05). The mRNA expression of TLR4 and NF-kappaB in the test group were significantly higher than in the control group. By contrast, the mRNA expression of TLR9 was significantly lower in the test group, and differences were statistically significant (P<0.05). Thus, the increased mRNA expression of TLR4 and NF-kappaB, and decreased mRNA expression of TLR9 during NEC may be an important inflammatory mechanism of the disease. PMID- 27357506 TI - Host specificity in a diverse Neotropical tick community: an assessment using quantitative network analysis and host phylogeny. AB - BACKGROUND: Host specificity is a fundamental determinant of tick population and pathogen transmission dynamics, and therefore has important implications for human health. Tick host specificity is expected to be particularly high in the tropics, where communities of ticks, hosts and pathogens are most diverse. Yet the degree to which tropical tick species are host-specific remains poorly understood. Combining new field data with published records, we assessed the specificity of tick-host associations in Panama, a diverse Neotropical region. METHODS: The resulting dataset includes 5,298 adult ticks belonging to 41 species of eight genera that were directly collected from 68 vertebrate host species of 17 orders. We considered three important aspects of tick host specificity: (i) the relative ecological importance of each host species (structural specificity); (ii) relatedness among host species (phylogenetic specificity); and (iii) spatial scale-dependence of tick-host relationships (geographical specificity). Applying quantitative network analyses and phylogenetic tools with null model comparisons, we assessed the structural and phylogenetic specificity across three spatial scales, ranging from central Panama to countrywide. Further, we tested whether species-rich tick genera parasitized a wider variety of hosts than species-poor genera, as expected when ticks specialize on different host species. RESULTS: Most tick species showed high structural and/or phylogenetic specificity in the adult stage. However, after correcting for sampling effort, we found little support for geographical specificity. Across the three scales, adult ticks tended to be specific to a limited number of host species that were phylogenetically closely related. These host species in turn, were parasitized by tick species from distinct genera, suggesting switching among distantly related hosts is common at evolutionary timescales. Further, there was a strong positive relationship between the taxonomic richness of the tick genera and that of their hosts, consistent with distinct tick species being relatively specific to different host species. CONCLUSIONS: Our results indicate that in the adult stage, most ticks in the diverse Neotropical community studied are host specialists. This contrasts with earlier assessments, but agrees with findings from other host-parasite systems. High host specificity in adult ticks implies high susceptibility to local tick-host co-extirpation, limited ability to colonize new habitats and limited potential for interspecific pathogen transmission. PMID- 27357507 TI - Determinants of non-adherence to disease-modifying therapies in multiple sclerosis: A cross-Canada prospective study. AB - BACKGROUND: Poor adherence to the disease-modifying therapies (DMTs) for multiple sclerosis (MS) may attenuate clinical benefit. A better understanding of characteristics associated with non-adherence could improve outcomes. OBJECTIVE: To evaluate characteristics associated with non-adherence to injectable DMTs. METHODS: Consecutive patients from four Canadian MS Clinics were assessed at three time points over two years. Clinical and demographic information included self-reported DMT use, missed doses in the previous 30 days, health behaviors, and comorbidities. Non-adherence was defined as <80% of expected doses taken. We employed generalized estimating equations to examine characteristics associated with non-adherence at all time points with findings reported as adjusted odds ratios (OR). RESULTS: In all, 485 participants reported use of an injectable DMT, of whom 107 (22.1%) were non-adherent over the study period. Non-adherence was associated with a lower Expanded Disability Status Scale score (0-2.5 vs 3.0-5.5, OR: 1.80; 95% confidence interval (CI): 1.06-3.04), disease duration (?5 vs <5 years, OR: 2.23; 95% CI: 1.10-4.52), alcohol dependence (OR: 2.14; 95% CI: 1.23 3.75), and self-reported cognitive difficulties, measured by the Health Utilities Index-3 (OR: 1.55; 95% CI: 1.08-2.22). CONCLUSIONS: Nearly one-quarter of participants were non-adherent during the study. Alcohol dependence, perceived cognitive difficulties, longer disease duration, and mild disability status were associated with non-adherence. These characteristics may help healthcare professionals identify patients at greatest risk of poor adherence. PMID- 27357508 TI - Combined effects of proinflammatory cytokines and intermittent cyclic mechanical strain in inhibiting osteogenicity in human periodontal ligament cells. AB - Mechanical strain plays an important role in bone formation and resorption during orthodontic tooth movement. The mechanism has not been fully studied, and the process becomes complex with increased amounts of periodontal patients seeking orthodontic care. Our aims were to elucidate the combined effects of proinflammatory cytokines and intermittent cyclic strain (ICS) on the osteogenic capacity of human periodontal ligament cells. Cultured human periodontal ligament cells were exposed to proinflammatory cytokines (interleukin-1beta 5 ng/mL and tumor necrosis factor-alpha 10 ng/mL) for 1 and 5 days, and ICS (0.5 Hz, 12% elongation) was applied for 4 h per day. The autocrine of inflammatory cytokines was measured by enzyme-linked immunosorbent assay. The expression of osteoblast markers runt-related transcription factor 2 and rabbit collagen type I was determined using real-time polymerase chain reaction and Western blot. The osteogenic capacity was also detected by alkaline phosphatase (ALP) staining, ALP activity, and alizarin red staining. We demonstrated that ICS impaired the osteogenic capacity of human periodontal ligament cells when incubated with proinflammatory cytokines, as evidenced by the low expression of ALP staining, low ALP activity, reduced alizarin red staining, and reduced osteoblast markers. These data, for the first time, suggest that ICS has a negative effect on the inductive inhibition of osteogenicity in human PDL cells mediated by proinflammatory cytokines. PMID- 27357510 TI - Abstracts of the 5th Congress of the Psoriasis International Network, 7-9 July 2016, Paris. PMID- 27357509 TI - Genomic ancestry estimation quantifies use of wild species in grape breeding. AB - BACKGROUND: Grapes are one of the world's most valuable crops and most are made into wine. Grapes belong to the genus Vitis, which includes over 60 inter-fertile species. The most common grape cultivars derive their entire ancestry from the species Vitis vinifera, but wild relatives have also been exploited to create hybrid cultivars, often with increased disease resistance. RESULTS: We evaluate the genetic ancestry of some of the most widely grown commercial hybrids from North America and Europe. Using genotyping-by-sequencing (GBS), we generated 2482 SNPs and 56 indels from 7 wild Vitis, 7 V. vinifera, and 64 hybrid cultivars. We used a principal component analysis (PCA) based ancestry estimation procedure and verified its accuracy with both empirical and simulated data. V. vinifera ancestry ranged from 11 % to 76 % across hybrids studied. Approximately one third (22/64) of the hybrids have ancestry estimates consistent with F1 hybridization: they derive half of their ancestry from wild Vitis and half from V. vinifera. CONCLUSIONS: Our results suggest that hybrid grape breeding is in its infancy. The distribution of V. vinifera ancestry across hybrids also suggests that backcrosses to wild Vitis species have been more frequent than backcrosses to V. vinifera during hybrid grape breeding. This pattern is unusual in crop breeding, as it is most common to repeatedly backcross to elite, or domesticated, germplasm. We anticipate our method can be extended to facilitate marker-assisted selection in order to introgress beneficial wild Vitis traits, while allowing for offspring with the highest V. vinifera content to be selected at the seedling stage. PMID- 27357511 TI - Preoperative inflammation increases the risk of infection after elective colorectal surgery: results from a prospective cohort. AB - BACKGROUND: Septic complications after colorectal surgery are frequent and sometimes life threatening. It is well known that inflammation impairs the healing process. It has been suggested that preoperative ongoing inflammation could increase the risk of postoperative infections. This study aimed to elucidate the role of preoperative inflammation on postoperative infectious complications and to understand if, through biological markers, it is possible to identify preoperatively patients at higher risk of infection. METHODS: A prospective, observational study was conducted in three centers from November 2011 to April 2014. Consecutive patients undergoing elective colorectal surgery with anastomosis were included. Any ongoing infection was an exclusion criterion. C-reactive protein, albumin, prealbumin, and procalcitonin plasma levels were measured preoperatively. Postoperative infections were recorded according to the definitions of the Centers for Diseases Control. The areas under the receiver operating characteristic curve were analyzed and compared to assess the accuracy of each preoperative marker. RESULTS: Four-hundred and seventy two patients were analyzed. Infectious complications occurred in 118 patients (25 %) and mortality in 6 patients (1.3 %). In the univariate analysis, preoperative C-reactive protein and albuminemia were found significantly associated with postoperative infectious complications (P = 0.008 and P = 0.0002, respectively). Areas under the ROC curve for preoperative C-reactive protein and albuminemia were 0.57and 0.62, respectively. CONCLUSIONS: This study confirms the association between preoperative inflammatory activity, hypoalbuminemia, and the onset of infections after surgery. Trials aiming to decrease the inflammatory activity before surgery in order to prevent postoperative complications are warranted. PMID- 27357512 TI - Health anxiety symptoms in children and adolescents diagnosed with OCD. AB - Health anxiety (HA) is an overlooked area in paediatric research. Little is known about the occurrence of HA symptoms in a child and adolescent psychiatric setting, and there are no age-appropriate diagnostic criteria and only limited number of assessment tools. It is therefore likely that HA is seen as part of obsessive-compulsive disorder (OCD) due to construct overlap and the diagnostic uncertainty of HA in this age group. In the present study, the extent of HA symptoms was investigated in 94 children and adolescents with a primary ICD-10 diagnosis of OCD. Self-reported HA symptoms were assessed using the Childhood Illness Attitude Scales. Clinician-rated OCD symptoms and severity were measured using the Children's Yale Brown Obsessive Compulsive Scale. Information on socio demographics was obtained from the child's/adolescent's medical record. The distribution of HA symptoms resembled a normal curve shifted to the right compared with a normal population of Danish children, and 30 % presented with high HA symptoms. Chi-squared tests were used to examine the proportion of children and adolescents with high HA symptoms in relation to various clinical characteristics. Clinician-rated illness worries and comorbid anxiety disorder were associated with high self-reported HA symptoms. The results contribute to the understanding of how HA and OCD overlap conceptually in young patients and bring attention to the need for improved recognition of OCD patients dominated by illness worries. Further research in the description of childhood HA is important in order to understand whether HA is a distinct disorder early in life. PMID- 27357514 TI - Evidence from prospective cohort studies did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review. AB - OBJECTIVES: National dietary guidelines were introduced in 1977 and 1983, by the USA and UK governments to reduce coronary heart disease (CHD) mortality by reducing dietary fat intake. Our 2015 systematic review examined randomised controlled trial (RCT) evidence available to the dietary committees at the time; we found no support for the recommendations to restrict dietary fat. What epidemiological evidence was available to the dietary guideline committees in 1983? METHODS: A systematic review of prospective cohort studies, published prior to 1983, which examined the relationship between dietary fat, serum cholesterol and the development of CHD. RESULTS: Across 6 studies, involving 31 445 participants, there were 1521 deaths from all-causes and 360 deaths from CHD during the mean follow-up of 7.5+/-6.2 years. The death rates were 4.8% and 1.1% from all-causes and CHD respectively. One study included men with previous heart disease. The death rate from CHD for those with, and without previous myocardial infarction was 20.9% and 1.0% respectively. None of the six studies found a significant relationship between CHD deaths and total dietary fat intake. One of the six studies found a correlation between CHD deaths and saturated dietary fat intake across countries; none found a relationship between CHD deaths and saturated dietary fat in the same population. CONCLUSIONS: 1983 dietary recommendations for 220 million US and 56 million UK citizens lacked supporting evidence from RCT or prospective cohort studies. The extant research had been undertaken exclusively on males, so lacked generalisability for population-wide guidelines. PMID- 27357513 TI - Low expression of centrosomal protein 78 (CEP78) is associated with poor prognosis of colorectal cancer patients. AB - BACKGROUND: Centrosomal protein 78 (CEP78) has been characterized as a component of the centrosome required for the regulation of centrosome-related events during the cell cycle, but its role in human cancers remains unclear. This study aimed to investigate the role and the clinical value of CEP78 in colorectal cancer (CRC). METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry were performed to examine CEP78 expression in CRC tissues and adjacent noncancerous tissues. The association between CEP78 expression and clinical outcomes of CRC patients was determined. The effect of CEP78 on cell growth was examined in vitro by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H tetrazolium bromide (MTT) assay, colony formation, and flow cytometry assays and in vivo using a nude mouse model. RESULTS: The expression level of CEP78 was significantly lower in tumor tissues than in the adjacent normal tissues (P < 0.01). Low CEP78 expression was significantly associated with poor differentiation (P = 0.003), large tumor size (P = 0.017), lymphatic metastasis (P = 0.034), distant metastasis (P = 0.029), and advanced stage (P = 0.011). Kaplan-Meier analysis indicated that patients with low CEP78 expression had shorter survival than those with high CEP78 expression (P < 0.01). Overexpression of CEP78 in CRC cells significantly reduced cell viability and colony formation in vitro and halted tumor growth in vivo. Further study showed that CEP78 reintroduction in CRC cells resulted in G2/M phase arrest rather than cell apoptosis. CONCLUSIONS: CEP78 might function as a tumor suppressor and serve as a novel prognostic marker in CRC. PMID- 27357516 TI - The angiogenic effect of dracorhodin perchlorate on human umbilical vein endothelial cells and its potential mechanism of action. AB - Hyperglycemia is the key clinical feature of diabetes, and may induce refractory wound lesions and impaired angiogenesis. Dracorhodin perchlorate (Dra) is the major ingredient of dragon's blood and it has been used as a medicine to treat chronic wounds, such as diabetic foot, since ancient times in many cultures. The current study aimed to investigate the effect of Dra on human umbilical vein endothelial cells (HUVECs) under high-glucose (HG) stimulation and its potential mechanism. Dra was observed to increase the multiplication capacity of HUVECs both under low glucose (LG) and HG concentrations. Additionally, migration and tube formation in HUVECs was facilitated by Dra. The expression levels of Ras, mitogen-activated protein kinase (MAPK) and vascular endothelial growth factor, which are key components of the Ras/MAPK pathway, were upregulated following Dra treatment. The present study is the first report, to the best of our knowledge, of the effects of Dra on wound healing, and the association with the Ras/MAPK signaling pathway. PMID- 27357517 TI - The de novo missense mutation N117S in skeletal muscle alpha-actin 1 causes a mild form of congenital nemaline myopathy. AB - Nemaline myopathy (NM) constitutes a spectrum of primary skeletal muscle disorders, the diagnosis of which is based on muscle weakness and the visualization of nemaline bodies in muscle biopsies. Mutations in several NM causal genes have been attributed to the majority of NM cases, particularly mutations in nebulin and skeletal muscle alpha-actin 1 (ACTA1), which are responsible for ~70% of cases; therefore, a genetic diagnostic strategy using targeted gene sequencing may potentially improve the diagnosis of suspected NM. The present study identified a de novo mutation in ACTA1 (c.350A>G; p.Asn117Ser) in a Chinese patient using target-capture sequencing of a panel containing 125 known causal genes for inherited muscle diseases. Clinical analyses revealed that the case described in the present study exhibited a relatively mild phenotype with regards to muscle weakness, as compared with more severe phenotypes reported in several other patients with the same mutation, thus suggesting the existence of genetic modifiers. In conclusion, this approach may be helpful for the identification of clinically undiagnosed patients with highly heterogeneous disorders. PMID- 27357515 TI - Human papillomavirus and lung cancinogenesis: an overview. AB - Lung cancer is the most common cause of cancer deaths worldwide. Although tobacco smoking is considered to be the main risk factor and the most well-established risk factor for lung cancer, a number of patients who do not smoke have developed this disease. This number varies between 15 % to over one-half of lung cancer cases, and the deaths from lung cancer in non-smokers are increasing every year. There are many other agents that are thought to be etiological, including diesel exhaust exposure, metals, radiation, radon, hormonal factors, cooking oil, air pollution and infectious diseases, such as human papillomavirus (HPV). Studies in various parts of the world have detected HPV DNA at different rates in lung tumors. However, the role of HPV in lung cancer is still unclear. Thus, in this review, we investigated some molecular mechanisms of HPV protein activity in host cells, the entry of HPV into lung tissue and the possible route used by the virus to reach the lung cells. PMID- 27357518 TI - Biological activities of suilysin: role in Streptococcus suis pathogenesis. AB - Streptococcus suis is an important swine and zoonotic pathogen equipped with several virulence factors. The pore-forming toxins are the most abundant bacterial toxins and classified as critical virulence (associated) factors of several pathogens. The role of suilysin (SLY), a pore-forming cholesterol dependent cytolysin of S. suis, as a true virulence factor is under debate. Most of the bacterial toxins have been reported to modulate the host immune system to facilitate invasion and subsequent replication of bacteria within respective host cells. SLY has been demonstrated to play an important role in the pathogenesis of S. suis infection and inflammatory response in vitro and in vivo. This review highlights the contributions of SLY to the pathogenicity of S. suis. It will address its role during the development of S. suis meningitis in pigs, as well as humans, and discuss SLY as a potential vaccine candidate. PMID- 27357519 TI - The first sugar of the repeat units is essential for the Wzy polymerase activity and elongation of the O-antigen lipopolysaccharide. AB - In the Wzx/Wzy-dependent assembled pathway, the assembled O-antigen repeat units are translocated from the cytosolic to the periplasmic face of the inner membrane by a Wzx translocase and then polymerized by the integral membrane protein Wzy to form a glycan chain. We demonstrate that the activity of the Escherichia coli O antigen polymerase (Wzy) is dependent on the first sugar of the O-antigen repeat unit to produce the O-antigen polymerization and therefore, there is a need for a concerted action with the enzyme transferring the initial HexNAc to undecaprenyl phosphate (UDP-HexNAc: polyprenol-P HexNAc-1-P transferase). Furthermore, in the case of Aeromonas hydrophila Wzy-O34 polymerization activity, the enzyme is permissive with the sugar at the nonreducing end of the O-antigen repeat unit. PMID- 27357520 TI - Characterization of unrelated clinical Legionella pneumophila isolates in Catalonia by monoclonal subgrouping and sequence-based typing. AB - AIM: To characterize the genetic diversity of unrelated Legionella pneumophila clinical isolates in Catalonia and compare with other European regions. METHODS: 95 unrelated isolates were analyzed using monoclonal antibodies and sequence based typing, 1989-2013. RESULTS: The isolates showed a high diversity (IOD 0.964) with a predominance of some profiles (ST37-Phialdelphia, ST23-Philadelphia and ST1-OLDA). All regions had predominant sequence types (STs) that differed between regions, and only 3% of STs were shared between the three regions. CONCLUSION: L. pneumophila clinical isolates from Catalonia presented a high diversity and can be used in epidemiological surveillance studies. The heterogeneous predominance of STs between European regions suggested a relationship between geographical distribution and virulence of some STs. PMID- 27357521 TI - Potential strategies for the eradication of multidrug-resistant Gram-negative bacterial infections. AB - Antimicrobial resistance is one of the leading threats to society. The increasing burden of multidrug-resistant Gram-negative infection is particularly concerning as such bacteria are demonstrating resistance to nearly all currently licensed therapies. Various strategies have been hypothesized to treat multidrug-resistant Gram-negative infections including: targeting the Gram-negative outer membrane; neutralization of lipopolysaccharide; inhibition of bacterial efflux pumps and prevention of protein folding. Silver and silver nanoparticles, fusogenic liposomes and nanotubes are potential strategies for extending the activity of licensed, Gram-positive selective, antibiotics to Gram-negatives. This may serve as a strategy to fill the current void in pharmaceutical development in the short term. This review outlines the most promising strategies that could be implemented to solve the threat of multidrug-resistant Gram-negative infections. PMID- 27357523 TI - Sequence-Specific DNA Photosplitting of Crosslinked DNAs Containing the 3 Cyanovinylcarbazole Nucleoside by Using DNA Strand Displacement. AB - An oligodeoxynucleotide (ODN) containing the ultrafast reversible 3 cyanovinylcarbazole ((CNV) K) photo-crosslinker was photo-crosslinked to a complementary strand upon exposure to 366 nm irradiation and photosplit by use of 312 nm irradiation. In this paper we report that the photoreaction of (CNV) K on irradiation at 366 nm involves a photostationary state and that its reaction can be controlled by temperature. Guided by this new insight, we proposed and have now demonstrated previously unknown photosplitting of (CNV) K aided by DNA strand displacement as an alternative to heating. The photo-crosslinked double-stranded DNA (dsDNA) underwent >80 % photosplitting aided by DNA strand displacement on irradiation at 366 nm without heating. In this photosplitting based on DNA strand displacement, the relative thermal stability of the invader strand with respect to the template strands plays an important role, and an invader strand/template strand system that is more stable than the passenger strand/template strand system induces photosplitting without heating. This new strand-displacement-aided photosplitting occurred in a sequence-specific manner through irradiation at 366 nm in the presence of an invader strand. PMID- 27357522 TI - Prolonged carriage and potential onward transmission of carbapenemase-producing Enterobacteriaceae in Dutch travelers. AB - AIM: The aim was to study acquisition and persistence of carbapenemase-producing Enterobacteriaceae (CPE) among travelers. MATERIALS & METHODS: Stools from 2001 travelers and 215 nontraveling household members, collected before and immediately post-travel as well as 1, 3, 6 and 12 months upon return, were screened for CPE. RESULTS: Five travelers, all visiting Asia outside the Indian subcontinent, acquired CPE. One traveler persistently carried the same OXA-244 CPE up to 6 months post-travel. Three months after travel, her co-traveling spouse also became positive for this OXA-244 CPE strain, suggesting clonal transmission within this household. CONCLUSION: Acquisition of CPE is not restricted to travelers to the Indian subcontinent and/or to travelers seeking healthcare during travel and can persist up to at least 6 months post-travel. PMID- 27357524 TI - Positive association of the androgen receptor CAG repeat length polymorphism with the risk of prostate cancer. AB - Prostate cancer (PC) is the most frequently diagnosed cancer in Ecuador (15.6%). The androgen receptor gene codes for a protein that has an androgen-binding domain, DNA-binding domain and N-terminal domain, which contains two polymorphic trinucleotide repeats (CAG and GGC). The aim of the present study was to determine whether variations in the number of repetitions of CAG and GGC are associated with the pathological features and the risk of developing PC. The polymorphic CAG and GGC repeat lengths in 108 mestizo patients with PC, 148 healthy mestizo individuals, and 78 healthy indigenous individuals were examined via a retrospective case-control study. Genotypes were determined by genomic sequencing. The results demonstrated that patients with <=21 CAG repeats have an increased risk of developing PC [odds ratio (OR)=2.99, 95% confidence interval (CI) =1.79-5.01; P<0.001]. The presence of <=21 CAG repeats was also associated with a tumor stage >=T2c (OR=4.75; 95% CI=1.77-12.72; P<0.005) and a Gleason score >=7 (OR=2.9; 95% CI=1.1-7.66; P=0.03). In addition, the combination of <=21 CAG and >=17 GGC repeats was associated with the risk of developing PC (OR=2.42; 95% CI=1.38-4.25; P=0.002) and with tumor stage >=T2c (OR=2.77; 95% CI=1.13-6.79; P=0.02). In conclusion, the histopathological characteristics and PC risk in Ecuadorian indigenous and mestizo populations differs in association with the CAG repeats, and the combination of CAG and GGC repeats. PMID- 27357525 TI - Pomegranate seed oil nanoemulsions with selective antiglioma activity: optimization and evaluation of cytotoxicity, genotoxicity and oxidative effects on mononuclear cells. AB - CONTEXT: Glioma is a malignant brain tumor with rapid proliferation, infiltrative growth, poor prognosis and it is chemoresistent. Pomegranate seed oil (PSO) has antioxidant, anti-inflammatory and antitumor properties. This study showed the optimization of PSO nanoemulsions (NEs) as an alternative for glioma treatment. OBJECTIVE: The study aimed to evaluate PSO NEs cytotoxicity on human blood cells and antiglioma effects against C6 cells. MATERIALS AND METHODS: NEs were prepared by the spontaneous emulsification method, using PSO at 1.5 and 3.0%, and were evaluated regarding their physical stability and antioxidant activity. Toxicity evaluations in human blood cells were performed in terms of cell viability, genotoxicity, lipid peroxidation, protein carbonylation, catalase activity and hemolysis at 0.1, 0.25 and 0.5 mg/mL PSO, after a 72-h incubation period. In vitro antitumor effect was determined against glioma cells after 24 and 48 h, and astrocytes were used as a non-transformed cell model. RESULTS: Formulations presented droplet size below 250 nm, low polydispersity index, negative zeta potential and pH in the acid range. NEs and PSO had scavenging capacity around 30% and promoted a proliferative effect in mononuclear cells, increasing about 50% cell viability. No genotoxic and oxidative damage was observed in lipid peroxidation, protein carbonylation and catalase activity evaluations for NEs. Hemolysis study showed a hemolytic effect at high concentrations. Moreover, formulations reduced only tumor cell viability to 47%, approximately. DISCUSSION AND CONCLUSION: Formulations are adequate and safe for intravenous administration. Besides, in vitro antitumor activity indicates that NEs are promising for glioma treatment. PMID- 27357526 TI - The impact of hypertension on leukocyte telomere length: a systematic review and meta-analysis of human studies. AB - Shortened leukocyte telomere length (LTL) is a novel biomarker for age and age related diseases. Several epidemiological studies have examined the association between telomere length in surrogate tissues (for example, blood cells) and hypertension, and meanwhile the majority of studies reported an association some individual studies do not. We carried out a systematic review and meta-analysis to address the hypothesis that, in humans, telomere length is related with hypertension. Searches were conducted in Pubmed by September 2015 and reference lists of retrieved citations were hand searched. Eligible studies measured telomeres for both hypertensive and normotensive subjects. No restrictions were placed on sample size, publication type, age or gender. We calculated summary estimates using fixed and random effects meta-analysis. Publication bias and heterogeneity among studies were further tested. Meta-analyses from 3097 participants (1415 patients with hypertension and 1682 control subjects) showed a significant standardized mean difference between LTL in hypertensive patients and controls, either in the fixed (P<5 * 10-6) or the random model (P<0.005). Heterogeneity among studies was substantial (Q-statistic P-value <0.001, I2 97.73%). Sensitivity analysis indicated that no single study changed the standardized mean difference qualitatively (0.022> random model P-value >0.002). Egger's test for asymmetry of effect sizes (intercept+/-s.e.=-7.278+/-3.574; P=0.072) did not show evidence for strong study publication bias. Leukocyte telomeres may be shorter in hypertensive than in normotensive individuals. Larger studies controlling for confounder effects are needed to confirm these findings and further explore sources of heterogeneity. PMID- 27357529 TI - Investigation of JAKs/STAT-3 in lipopolysaccharide-induced intestinal epithelial cells. AB - Janus-activated kinase (JAKs)-signal transducer and activator of transcription 3 (STAT-3) signalling play critical roles in immunoregulation and immunopathology, which involve inflammatory responses and enteritis. JAK phosphorylates STAT-3 in response to stimulation by cytokines or growth factors, and then activates or represses the gene expression. STAT-3 is activated persistently in cancer cells and contributes to the malignant progression of various types of cancer and inflammation. To elucidate the different roles of JAKs in the activation of STAT 3, the lipopolysaccharide-induced primary intestinal epithelial cell (IEC) acute inflammatory model was established. Small interference RNAs (siRNAs) were then employed to attenuate the expression levels of JAKs. Real-time quantitative reverse transcription-polymerase chain reaction (PCR) (qRT-PCR) revealed that JAK mRNA levels were reduced efficiently by JAK-specific siRNAs. Under the IEC inflammatory model transfected with si-JAK, which equates to effective silencing, qRT-PCR and Western blot assays, suggested that knockdowns of JAK attenuated the JAK-induced down-regulation of STAT-3 at the mRNA or protein levels. In particular, JAK1 played a key role, which was consistent with the RNA-Seq results. Subsequently, the expression levels of proinflammatory cytokines interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha were down-regulated in the IEC inflammatory model transfected with si-JAK1. JAK1 appears as a direct activator for STAT-3, whereas treatments targeting JAK1 repressed STAT-3 sufficiently pathways in the IEC inflammatory model. Therefore, the control of JAK1 using siRNAs has the potential to be an effective strategy against enteritis. PMID- 27357530 TI - Bone-Albumin filling decreases donor site morbidity and enhances bone formation after anterior cruciate ligament reconstruction with bone-patellar tendon-bone autografts. AB - PURPOSE: Donor site pain affects 32-43 % of patients after anterior cruciate ligament surgery when the autograft is freshly harvested bone-patellar tendon bone tissue. Our aim was to compare functional and morphological differences between donor sites with and without serum albumin-coated bone allograft filling. METHODS: After harvesting and implanting the graft, the tibia site was filled with either fresh autologous cancellous bone enhanced with albumin-coated allograft or autologous bone alone. The patella site was filled either with albumin-coated allograft or with blood clot. Knee function was evaluated by the VISA, Lysholm and IKDC scores and a visual analog scale of pain during standing, kneeling and crouching after six weeks and six months. Computed tomography was performed at six months for morphological evaluation. RESULTS: At six weeks, both groups were still recovering from surgery and the overall knee function was still impaired but the functional scores were significantly higher in the Bone-Albumin group. The pain with crouching and kneeling was also lower as compared to controls. At six months, the knee function scores were close to normal, with a slight decrease in the controls. Pain at kneeling was still prominent in the controls, but significantly lower in the Bone-Albumin group. Computed tomography showed significantly smaller bone defects and higher bone density in the Bone Albumin group. CONCLUSIONS: Results from the present study indicate that donor site pain, a disturbing long-term side effect of bone-patellar tendon-bone surgery, is significantly reduced if bone buildup in the patella and the tibia is augmented by serum albumin-coated bone allografts. PMID- 27357528 TI - Adherence to Internet-Based Mobile-Supported Stress Management: A Pooled Analysis of Individual Participant Data From Three Randomized Controlled Trials. AB - BACKGROUND: Nonadherence to treatment is a prevalent issue in Internet interventions. Guidance from health care professionals has been found to increase treatment adherence rates in Internet interventions for a range of physical and mental disorders. Evaluating different guidance formats of varying intensity is important, particularly with respect to improvement of effectiveness and cost effectiveness. Identifying predictors of nonadherence allows for the opportunity to better adapt Internet interventions to the needs of participants especially at risk for discontinuing treatment. OBJECTIVE: The goal of this study was to investigate the influence of different guidance formats (content-focused guidance, adherence-focused guidance, and administrative guidance) on adherence and to identify predictors of nonadherence in an Internet-based mobile-supported stress management intervention (ie, GET.ON Stress) for employees. METHODS: The data from the groups who received the intervention were pooled from three randomized controlled trials (RCTs) that evaluated the efficacy of the same Internet-based mobile-supported stress management intervention (N=395). The RCTs only differed in terms of the guidance format (content-focused guidance vs waitlist control, adherence-focused guidance vs waitlist control, administrative guidance vs waitlist control). Adherence was defined by the number of completed treatment modules (0-7). An ANOVA was performed to compare the adherence rates from the different guidance formats. Multiple hierarchical linear regression analysis was conducted to evaluate predictors of nonadherence, which included gender, age, education, symptom-related factors, and hope for improvement. RESULTS: In all, 70.5% (93/132) of the content-focused guidance sample, 68.9% (91/132) of the adherence-focused guidance sample, and 42.0% (55/131) of the participants in the administrative guidance sample completed all treatment modules. Guidance had a significant effect on treatment adherence (F2,392=11.64, P<.001; omega(2)=.05). Participants in the content-focused guidance (mean 5.70, SD 2.32) and adherence-focused guidance samples (mean 5.58, SD 2.33) completed significantly more modules than participants in the administrative guidance sample (mean 4.36, SD 2.78; t223=4.53, P<.001; r=.29). Content-focused guidance was not significantly associated with higher adherence compared to adherence focused guidance (t262=0.42, P=.67; r=.03). The effect size of r=.03 (95% CI 0.09 to 0.15) did not pass the equivalence margin of r=.20 and the upper bound of the 95% CI lay below the predefined margin, indicating equivalence between adherence-focused guidance and content-focused guidance. Beyond the influence of guidance, none of the predictors significantly predicted nonadherence. CONCLUSIONS: Guidance has been shown to be an influential factor in promoting adherence to an Internet-based mobile-supported stress management intervention. Adherence-focused guidance, which included email reminders and feedback on demand, was equivalent to content-focused guidance with regular feedback while requiring only approximately a quarter of the coaching resources. This could be a promising discovery in terms of cost-effectiveness. However, even after considering guidance, sociodemographic, and symptom-related characteristics, most interindividual differences in nonadherence remain unexplained. CLINICAL TRIAL: DRKS00004749; http://drks-neu.uniklinik freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL _ID=DRKS00004749 (Archived by WebCite at http://www.webcitation.org/6QiDk9Zn8); DRKS00005112; http://drks-neu.uniklinik-freiburg. de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00005112 (Archived by WebCite at http://www.webcitation.org/6QiDysvev); DRKS00005384; http://drks neu.uniklinik-freiburg.de/ drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00005384 (Archived by WebCite at http://www.webcitation.org/6QiE0xcpE). PMID- 27357531 TI - Is tibial cut navigation alone sufficient in medial unicompartmental knee arthroplasty? Continuous series of fifty nine procedures. AB - PURPOSE: Our purpose was to assess medial unicompartmental knee arthroplasty with navigation alone for the tibial cut and limb alignment. We hypothesised that this technique could be used routinely in practice. METHODS: Outcome measures were tibial cut orientation and residual varus. Six-month post-operative radiographs of 59 knees were assessed. RESULTS: Tibial cut orientation was within 2 degrees of planned in 70.2 and 76.3 % of knees in the coronal and sagittal planes, respectively (49.1 % in both), within 4 degrees in 91.2 and 91.5 %, respectively (82.5 % in both). All coronal-plane errors were in varus. Excessive planed tibial slope was at risk of excessive varus of the tibial cut. The hip-knee-ankle angle was <=179 degrees in 81.4 % and the mechanical axis through Kennedy Zone 2 in 59.3 % of knees. Risk factors for inadequate varus were pre-operative hip-knee ankle angle >176 degrees and strictly articular varus. CONCLUSIONS: Our results are not as good as previously reported with this technique, but taking into account the factors of failure identified, we could enhance the results. PMID- 27357532 TI - Pre-Multidrug-Resistant Mycobacterium tuberculosis Infection Causing Fatal Enteric Disease in a Dog from a Family with History of Human Tuberculosis. AB - This report describes a fatal case of a pet dog with major enteric signs owned by a family that has experienced cases of pulmonary tuberculosis (TB) in the household. Clinical and epidemiological aspects, imaging data, microbiological, haematological and histopathological examinations were assessed to diagnosis of disease. gyrB-RFLP, spoligotyping and MIRU-VNTR allowed molecular detection of M. tuberculosis strain from S family. The resazurin microtiter assay indicated that all isolates were resistant to isoniazid, ethambutol, ciprofloxacin, ofloxacin, streptomycin and amikacin. The public health concerns related to canine tuberculosis and risk of the dissemination by pets of M. tuberculosis pre multidrug-resistant (PMD) to isoniazid, ethambutol and other first-line drugs used in human therapy of TB are discussed. We believe this to be the first report of PMD M. tuberculosis infection in a dog presenting mainly enteric manifestation, confirmed as S lineage by molecular methods, owned by a family in which TB has spread in the household for generations. PMID- 27357533 TI - The reaction current distribution in battery electrode materials revealed by XPS based state-of-charge mapping. AB - Morphologically complex electrochemical systems such as composite or nanostructured lithium ion battery electrodes exhibit spatially inhomogeneous internal current distributions, particularly when driven at high total currents, due to resistances in the electrodes and electrolyte, distributions of diffusion path lengths, and nonlinear current-voltage characteristics. Measuring and controlling these distributions is interesting from both an engineering standpoint, as nonhomogenous currents lead to lower utilization of electrode material, as well as from a fundamental standpoint, as comparisons between theory and experiment are relatively scarce. Here we describe a new approach using a deliberately simple model battery electrode to examine the current distribution in a electrode material limited by poor electronic conductivity. We utilize quantitative spatially resolved X-ray photoelectron spectroscopy to measure the spatial distribution of the state-of-charge of a V2O5 model electrode as a proxy measure for the current distribution on electrodes discharged at varying current densities. We show that the current at the electrode-electrolyte interface falls off with distance from the current collector, and that the current distribution is a strong function of total current. We compare the observed distributions with a simple analytical model which reproduces the dependence of the distribution on total current, but fails to predict the correct length scale. A more complete numerical simulation suggests that dynamic changes in the electronic conductivity of the V2O5 concurrent with lithium insertion may contribute to the differences between theory and experiment. Our observations should help inform design criteria for future electrode architectures. PMID- 27357534 TI - Antiarrhythmic activity of a new spiro-cyclic benzopyran activator of the cardiac mitochondrial ATP dependent potassium channels. AB - 'Compound A' (4(i)-(N-(4-acetamidobenzyl))-2,2-dimethyl-2,3-dihydro-5(i)H spiro[chromene-4,2(i)-[1,4]oxazinan]-5(i)-one) is a new spiro-cyclic benzopyran activator of the mitochondrial ATP-dependent potassium channels (mitoKATP). We researched the effect of compound A on ischemia/reperfusion (I/R)-induced ventricular arrhythmias. We also tested the hypothesis that the application of the activation of mitoKATP in combination with the inhibition of sarcolemmal ATP dependent potassium channels (sarcKATP) may produce a stronger antiarrhythmic effect. In anesthetized rats, myocardial ischemia was performed by ligating the left main coronary artery followed by reperfusion. At a dose of 10 mg/kg, compound A significantly decreased arrhythmia scores and the total length of arrhythmias, whereas this was found to be ineffective at a dose of 3 mg/kg. Pre treatment with 5-HD, a selective mitoKATP blocker, abolished the antiarrhythmic effect of compound A. Both diazoxide, a selective mitoKATP opener and HMR 1098, a selective sarcKATP blocker, significantly decreased the total length of arrhythmias. However, the combination of neither diazoxide nor compound A with HMR 1098 showed no additional therapeutic benefit. These results reveal that compound A may have a dose-dependent antiarrythmic effect, which is more pronounced than the antiarrhythmic effect of diazoxide. The antiarrhythmic effect of compound A may possibly depend on mitoKATP activation. PMID- 27357535 TI - Evaluation of the angiogenic potency of a novel exopolysaccharide produced by the MK1 bacterial strain. AB - Angiogenesis is an essential physiological step in wound healing and other regenerative processes. Here, we evaluated the angiogenic properties of an exopolysaccharide (EPS) secreted by MK1 (MK1-EPS), a novel bacterial strain isolated from Neungee mushrooms. MK1-EPS significantly increased human umbilical vein endothelial cell (HUVEC) proliferation, migration, and vascular tube formation. MK1-EPS enhanced the phosphorylation of extracellular signal-related kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, which are mitogen-activated protein kinases. In addition, the expression of p21 and intercellular adhesion molecule 1 (ICAM1), and phosphorylation of signal transducer and activator of transcription 3 (STAT3), but not of protein kinase B (AKT), were increased. Specific inhibitors of p38 (SB203580), ERK (PD98059), and JNK (SP600125) inhibited MK1-EPS-induced HUVEC proliferation, tube formation, and cell migration, and partially attenuated MKI-EPS-induced expression of p21 and ICAM1, and STAT3 phosphorylation. After surgical implantation into rabbit calvarial bone defects, new blood vessel formation was significantly higher with MK1-EPS composite bone granules than with granules alone, and new bone formation increased significantly. Therefore, MK1-EPS induces angiogenesis and may have potential for use as a bone regeneration agent in bone tissue engineering applications. PMID- 27357536 TI - Effect of lycopene on the blood-spinal cord barrier after spinal cord injury in mice. AB - The current study aimed to investigate the effect of lycopene on the blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) in a mouse model. Lycopene inhibited lipid peroxidation and oxidative DNA damage as a highly efficient antioxidant and free radical scavenger. Lycopene (4 mg/kg/d) was administrated immediately following SCI. The permeability of the BSCB and water content in the spinal cord tissue were evaluated. Additionally, levels of expression of tight junction proteins and heme oxygenase-1 (HO-1) were determined with Western blotting. An enzyme-linked immunosorbent assay analysis of spinal cord tissue homogenates was performed 48 h after SCI to evaluate the expression of inflammation-related cytokines. In addition, recovery of motor function was assessed 1 d, 2 d, 5 d, 10 d, and 15 d after SCI using the Basso Mouse Scale to score locomotion. Compared to the group with an untreated SCI, mice with an SCI treated with lycopene had significantly reduced spinal cord tissue water content and BSCB permeability. Furthermore, motor function of mice with an SCI was also greatly improved by lycopene administration. The expression of the proinflammatory factors TNF-alpha and NF-kB increased markedly 48 h after SCI, and their upregulation was significantly attenuated by lycopene treatment. The expression of molecules that protect tight junctions, zonula occluden-1 and claudin-5, was upregulated by lycopene treatment after SCI. Taken together, these results clearly indicate that lycopene attenuated SCI by promoting repair of the damaged BSCB, so lycopene is a novel and promising treatment for SCI in humans. PMID- 27357537 TI - Diverse distribution of Toxin-Antitoxin II systems in Salmonella enterica serovars. AB - Type II Toxin-Antitoxin systems (TAs), known for their presence in virulent and antibiotic resistant bacterial strains, were recently identified in Salmonella enterica isolates. However, the relationships between the presence of TAs (ccdAB and vapBC) and the epidemiological and genetic features of different non typhoidal Salmonella serovars are largely unknown, reducing our understanding of the ecological success of different serovars. Salmonella enterica isolates from different sources, belonging to different serovars and epidemiologically unrelated according to ERIC profiles, were investigated for the presence of type II TAs, plasmid content, and antibiotic resistance. The results showed the ubiquitous presence of the vapBC gene in all the investigated Salmonella isolates, but a diverse distribution of ccdAB, which was detected in the most widespread Salmonella serovars, only. Analysis of the plasmid toxin ccdB translated sequence of four selected Salmonella isolates showed the presence of the amino acid substitution R99W, known to impede in vitro the lethal effect of CcdB toxin in the absence of its cognate antitoxin CcdA. These findings suggest a direct role of the TAs in promoting adaptability and persistence of the most prevalent Salmonella serovars, thus implying a wider eco-physiological role for these type II TAs. PMID- 27357538 TI - Estrogen receptor beta1 in diffuse large B-cell lymphoma growth and as a prognostic biomarker. AB - Diffuse large B-cell lymphoma (DLBCL) shows a higher incidence in males versus females. Epidemiological studies have shown that female gender is a favorable prognostic factor, which may be explained by estrogens. Here we show that when grafting human DLBCL cells to immunocompromised mice, tumor growth in males is faster. When treating mice grafted with either germinal center or activated B cell like DLBCL cells with the selective estrogen receptor beta (ERbeta) agonist diarylpropionitrile, tumor growth was significantly inhibited. Furthermore, nuclear ERbeta1 expression analysis in primary DLBCL's by immunohistochemistry revealed expression in 89% of the cases. Nuclear ERbeta1 expression was in a univariate and multivariate analysis, an independent prognostic factor for adverse progression-free survival in Rituximab-chemotherapy treated DLBCL (p = 0.02 and p = 0.04, respectively). These results suggest that estrogen signaling through ERbeta1 is an interesting future therapeutic target for treatment of DLBCL, and that ERbeta1 expression can be used as a prognostic marker. PMID- 27357539 TI - Pironetin reacts covalently with cysteine-316 of alpha-tubulin to destabilize microtubule. AB - Molecules that alter the normal dynamics of microtubule assembly and disassembly include many anticancer drugs in clinical use. So far all such therapeutics target beta-tubulin, and structural biology has explained the basis of their action and permitted design of new drugs. However, by shifting the profile of beta-tubulin isoforms, cancer cells become resistant to treatment. Compounds that bind to alpha-tubulin are less well characterized and unexploited. The natural product pironetin is known to bind to alpha-tubulin and is a potent inhibitor of microtubule polymerization. Previous reports had identified that pironetin reacts with lysine-352 residue however analogues designed on this model had much lower potency, which was difficult to explain, hindering further development. We report crystallographic and mass spectrometric data that reveal that pironetin forms a covalent bond to cysteine-316 in alpha-tubulin via a Michael addition reaction. These data provide a basis for the rational design of alpha-tubulin targeting chemotherapeutics. PMID- 27357540 TI - Killing Glioma 'Stem-like' Cells via Drug-Induced Relocation of Endosomal Urokinase Proteins. AB - High grade gliomas (HGGs) are primary CNS cancers with more than 95% of patients experiencing tumor recurrence following radiation therapy, chemotherapy, and/or an anti-angiogenic therapy. Populations of glioma 'stem-like' cells (GSCs) exist in both proliferative and non-proliferative states and are capable of tumor regrowth. These GSCs survive within hypoxic tumor regions and avascular tumor margins, while retaining the capability to regenerate. Successful treatment of HGGs depends on therapeutic targeting of GSCs to avert tumor regeneration. Here, we review novel intracellular mechanisms by which 3-amino-5-arylamino-6-chloro-N (diaminomethylene) pyrazine-2-carboximide (UCD38B) and the much more potent 5' substituted arylamino compounds (cmpd 10357) irreversibly kill GSCs utilizing caspase-independent, programmed necrotic cell death. Drug-induced relocation of a subset of endosomes to perinuclear mitochondria triggers the mitochondrial release and nuclear translocation of apoptosis inducible factor (AIF) that is followed by nuclear condensation and cancer cell demise. This drug-induced endosomal 'mis-trafficking' affects a subset of endosomes containing proteins belonging to the urokinase plasminogen activator system (uPAS) and guided by lipoprotein receptor protein type 1 (LRP-1). UCD38B and congeners act intracellularly and bind to intracellular urokinase plasminogen activator (uPA) to disrupt uPA binding to PAI-1 and the endosomal LRP-1 guidance protein. These small molecules are cytotoxic to persistently hypoxic and acidotic HGG cell lines and to high grade gliomas from patient derived xenografts (PDX). Immunodeficient mice with intracerebral PDX glial tumors demonstrate drug-specific, AIF- mediated necrosis after 24h of treatment. The propensity of these small molecules to kill non-proliferating and proliferating hypoxic GSCs, suggests a potential synergistic therapeutic role with radiotherapy, anti-mitotic and anti-angiogenic therapies. PMID- 27357541 TI - Glucose Oncometabolism of Esophageal Cancer. AB - Metabolic reprograming contributes to esophageal tumorigenesis. A better understanding of how esophageal cancer (EC) cells reactivate primitive signaling to retain glucose metabolism under unfavorable conditions is essential for the development of therapeutic interventions to treat EC. Current achievements in the field of EC glucose metabolism have been critically reviewed to address several fundamental questions. These include: 1) the association of abnormal glucose metabolism and EC risk; 2) alterations of genes and/or proteins that contribute to glucose oncometabolism in EC; 3) signal transduction pathways that promote EC consumption of glucose; and, 4) targeting the glycolytic element or the EC dependency on excessive glucose consumption to prevent growth of EC caused by different genomic changes. PMID- 27357542 TI - Phytochemical Analysis with Antioxidant and Cytotoxicity Studies of the Bioactive Principles from Zanthoxylum capense (Small Knobwood). AB - BACKGROUND: Zanthoxylum capense (small knobwood) is a South African species known for a wide range of anecdotal uses. However, there is a dearth of information on its phytoconstitutional make-up, specifically its knobs, with only a few reports on the bioactive compounds that could justify its ethnomedicinal use. OBJECTIVES: This work aimed to identify the active principles in Z. capense and evaluate their cytotoxicity against breast cancer tumor cells. METHOD: Extracts from the stem bark, knobs and leaves were purified using chromatographic methods and characterized using spectroscopic techniques. Cytotoxicity of isolated compounds was evaluated on mammalian MCF-7, Caco-2 tumor cell lines and HEK295, a normal kidney cell line. RESULTS: The following compounds were isolated from the plant: a quaternary benzophenanthridine-type alkaloid (chelerythrine) along with its alkanoamine derivative (6-hydroxydihydrochelerythrine), an indolopyridoquinazoline alkaloid (rutaecarpine), an alkyl p-coumaric acid ester (dodecyl-trans-p-coumarate), a lignan (sesamin), a flavanol (catechin), two triterpenoids (lupeol and sitosterol) and two pigments (pheophytin a and lutein). In the cytotoxicity study, all tested samples decreased the viability of the MCF 7 tumor cells by at least 23% at concentration 1 MUg mL-1 and Caco-2 tumor cells by at least 15% at concentration 5 MUg mL-1 but a mild toxic effect on HEK295 across the tested samples. RESULTS: The following compounds were isolated from the plant: a quaternary benzophenanthridine-type alkaloid (chelerythrine) along with its alkanoamine derivative (6-hydroxydihydrochelerythrine), an indolopyridoquinazoline alkaloid (rutaecarpine), an alkyl p-coumaric acid ester (dodecyl-trans-p-coumarate), a lignan (sesamin), a flavanol (catechin), two triterpenoids (lupeol and sitosterol) and two pigments (pheophytin a and lutein). In the cytotoxicity study, all tested samples decreased the viability of the MCF 7 tumor cells by at least 23% at concentration 1 MUg mL-1 and Caco-2 tumor cells by at least 15% at concentration 5 MUg mL-1 but a mild toxic effect on HEK295 across the tested samples. PMID- 27357543 TI - Construction of an Anticancer Fusion Peptide (ACFP) Derived from Milk Proteins and an Assay of Anti-ovarian Cancer Cells in vitro. AB - BACKGROUND: Some bioactive peptides derived from natural resources or synthesized by rational design have been shown to have very good anticancer effects. We designed an anticancer fusion peptide (ACFP) based on the structure of bovine lactoferricin (LfcinB) and hexapeptide (PGPIPN) derived from bovine milk protein. OBJECTIVE: To prepare ACFP through genetic engineering and study its antiovarian cancer activity. METHOD: ACFP gene was produced by a flexible link arm connecting LfcinB and PGPIPN. ACFP was inductively expressed in Escherichia coli by the recombinant plasmid pGEX-KG-ACFP. ACFP was prepared and purified by affinity chromatography, and identified by polyacrylamide gel electrophoresis (PAGE), high performance liquid chromatography (HPLC) and mass spectrometry (MS). Recombinant lentivirus vectors were produced by cotransfecting 293T cells with constructed plasmid pLJM1-ACFP, envelope plasmid Delta8.91 and pVSVG using Lipofectamine. ACFP gene was transfected into ovarian cancer cells by pLJM1-ACFP lentivirus. Cell Viability was assayed by the methyl thiazolyl tetrazolium (MTT). The apoptosis of ovarian cancer SKOV3 cells was measured by flow cytometry and observed by Hoechst33258 staining. RESULTS: ACFP was successfully prepared and purified by genetic engineering. ACFP more effectively inhibited the viability of human ovarian cancer SKOV3 cells than the single parent peptides in vitro. ACFP was found to have no cytotoxicity towards untransformed cells. The ACFP gene in cancer cells infected with pLJM1-ACFP lentivirus could significantly inhibit the viability of SKOV3 cells and induce their apoptosis. CONCLUSION: ACFP is a potential therapeutic agent for the treatment of ovarian cancer. PMID- 27357544 TI - Synthesis, Molecular Docking Study and in vitro Anticancer Activity of Tetrazole Linked Benzochromene Derivatives. AB - BACKGROUND: Globally, cancer is regarded as one of the biggest health concern in humans and animals and is one of the most terrifying diseases. Therefore, there is a necessity for the discovery, development and improvement of novel antitumor drug molecules which could efficiently prevent proliferative pathways and clonal expansion of cells. Heterocyclic compounds like benzochromene play a key role in the development of current pharmaceuticals, natural resources, agriculture products, analytical reagents and dyes. Therefore, anticancer drugs show increased resistance, it is essential to designing the novel structured heterocyclic moieties to create potential anticancer agents with promising biological applications. OBJECTIVE: To synthesis a novel 1-(substitutedphenyl)-2 (1H-tetrazol-5-yl)-1H-benzo[f]chromene-3-amine derivatives for in vitro antitumour activity. METHOD: The reaction of 3-amino-1-(substitutedphenyl)-1H benzo[f]chromene-2-carbonitrile with sodium azide, ammonium chloride in dimethyl formamide solvent under reflux condition for 4 h afforded products (3a-k). The synthesized molecules were subjected to possible potential anti-tumour activity in vitro in four human cancer cell lines (MCF-7, Caco-2, HeLa and SKBR-3), and one human non-cancer cell line (HEK293), using the MTT cell viability assay. RESULTS: A novel series of products (3a-k) were synthesized with good yield and were identified with 1H NMR, 15N NMR, 13C NMR, FT-IR and HR-MS spectrum. The most potent compounds 3d, 3e, and 3f possessing the greatest cytotoxicity activity with IC50 values slightly higher (15-33 MUM) than that of 5-Fluorouracil (10-17 MUM), indicating their potential to be antitumor agents. The 3a, 3b, 3c, 3h, 3i and 3j compounds showed moderate activity. Additionally, a molecular docking analysis was conducted to predict the multi-drug resistance modulator behavior of synthesized compounds in the ATP binding site of P-glycoprotein. CONCLUSIONS: We synthesized and designated eleven novel derivatives of tetrazole linked benzochromenes (3a-k) and evaluated their anti-cancer activity. Additionally, the results from the docking studies were found to be in good agreement with the results from computational profiling. PMID- 27357545 TI - Quantitative deep mapping of the cultured podocyte proteome uncovers shifts in proteostatic mechanisms during differentiation. AB - The renal filtration barrier is maintained by the renal podocyte, an epithelial postmitotic cell. Immortalized mouse podocyte cell lines-both in the differentiated and undifferentiated state-are widely utilized tools to estimate podocyte injury and cytoskeletal rearrangement processes in vitro. Here, we mapped the cultured podocyte proteome at a depth of more than 8,800 proteins and quantified 7,240 proteins. Copy numbers of proteins mutated in forms of hereditary nephrotic syndrome or focal segmental glomerulosclerosis (FSGS) were assessed. We found that cultured podocytes express abundant copy numbers of endogenous receptors, such as tyrosine kinase membrane receptors, the G protein coupled receptor (GPCR), NPR3 (ANP receptor), and several poorly characterized GPCRs. The data set was correlated with deep mapping mRNA sequencing ("mRNAseq") data from the native mouse podocyte, the native mouse podocyte proteome and staining intensities from the human protein atlas. The generated data set was similar to these previously published resources, but several native and high abundant podocyte-specific proteins were not identified in the data set. Notably, this data set detected general perturbations in proteostatic mechanisms as a dominant alteration during podocyte differentiation, with high proteasome activity in the undifferentiated state and markedly increased expression of lysosomal proteins in the differentiated state. Phosphoproteomics analysis of mouse podocytes at a resolution of more than 3,000 sites suggested a preference of phosphorylation of actin filament-associated proteins in the differentiated state. The data set obtained here provides a resource and provides the means for deep mapping of the native podocyte proteome and phosphoproteome in a similar manner. PMID- 27357546 TI - Reduced ATGL-mediated lipolysis attenuates beta-adrenergic-induced AMPK signaling, but not the induction of PKA-targeted genes, in adipocytes and adipose tissue. AB - 5'-AMP-activated protein kinase (AMPK) is activated as a consequence of lipolysis and has been shown to play a role in regulation of adipose tissue mitochondrial content. Conversely, the inhibition of lipolysis has been reported to potentiate the induction of protein kinase A (PKA)-targeted genes involved in the regulation of oxidative metabolism. The purpose of the current study was to address these apparent discrepancies and to more fully examine the relationship between lipolysis, AMPK, and the beta-adrenergic-mediated regulation of gene expression. In 3T3-L1 adipocytes, the adipose tissue triglyceride lipase (ATGL) inhibitor ATGListatin attenuated the Thr(172) phosphorylation of AMPK by a beta3-adrenergic agonist (CL 316,243) independent of changes in PKA signaling. Similarly, CL 316,243-induced increases in the Thr(172) phosphorylation of AMPK were reduced in adipose tissue from whole body ATGL-deficient mice. Despite reductions in the activation of AMPK, the induction of PKA-targeted genes was intact or, in some cases, increased. Similarly, markers of mitochondrial content and respiration were increased in adipose tissue from ATGL knockout mice independent of changes in the Thr(172) phosphorylation of AMPK. Taken together, our data provide evidence that AMPK is not required for the regulation of adipose tissue oxidative capacity in conditions of reduced fatty acid release. PMID- 27357547 TI - Role of scleraxis in mechanical stretch-mediated regulation of cardiac myofibroblast phenotype. AB - The phenotype conversion of fibroblasts to myofibroblasts plays a key role in the pathogenesis of cardiac fibrosis. Numerous triggers of this conversion process have been identified, including plating of cells on solid substrates, cytokines such as transforming growth factor-beta, and mechanical stretch; however, the underlying mechanisms remain incompletely defined. Recent studies from our laboratory revealed that the transcription factor scleraxis is a key regulator of cardiac fibroblast phenotype and extracellular matrix expression. Here we report that mechanical stretch induces type I collagen expression and morphological changes indicative of cardiac myofibroblast conversion, as well as scleraxis expression via activation of the scleraxis promoter. Scleraxis causes phenotypic changes similar to stretch, and the effect of stretch is attenuated in scleraxis null cells. Scleraxis was also sufficient to upregulate expression of vinculin and F-actin, to induce stress fiber and focal adhesion formation, and to attenuate both cell migration and proliferation, further evidence of scleraxis mediated regulation of fibroblast to myofibroblast conversion. Together, these data confirm that scleraxis is sufficient to promote the myofibroblast phenotype and is a required effector of stretch-mediated conversion. Scleraxis may thus represent a potential target for the development of novel antifibrotic therapies aimed at inhibiting myofibroblast formation. PMID- 27357548 TI - Which coping strategies can predict beneficial feelings associated with prostate cancer? AB - AIMS AND OBJECTIVES: This study aimed to identify the extent to which different coping strategies can predict benefit finding in prostate cancer experiences. BACKGROUND: Although beginning evidence suggests that the capacity to find positives in adversity and find some benefit from cancer-associated experiences may be influenced by coping, little is known about which coping strategies can predict benefit finding in prostate cancer. DESIGN: Cross-sectional. METHOD: Data from men (n = 209) diagnosed with prostate cancer receiving hormone suppression therapy were analysed using descriptive statistics, bivariate correlations and backward stepwise multiple linear regression. Sociodemographic and clinical data, and self-report scales (17-item Benefit Finding Scale and Brief COPE) were used. RESULTS: Bivariate analyses showed significant correlations between 14 coping strategies and benefit finding in prostate cancer. Multiple linear regression modelling showed that the predictor variables 'acceptance', 'positive reframing' and 'turning to religion' explained 35% of the variance in dependant variable benefit finding when the other variables were controlled for. Of the three predictor variables, acceptance and positive reinterpretation were most strongly related to benefit finding. CONCLUSION: The self-reported coping strategies 'acceptance' and 'positive reframing' emerged as being most significantly predictive of benefit finding in this sample. 'Turning to religion' was also significant, but to a somewhat lesser extent in predicting benefit finding in the disruptive experience of prostate cancer. RELEVANCE TO CLINICAL PRACTICE: The use of positively oriented emotional coping strategies of 'acceptance', 'positive reframing' and 'turning to religion' are influential to benefit finding in prostate cancer. An understanding of the coping strategies that are predictive to benefit finding can assist clinicians to discern and target men who are more or less likely to find benefit, and to develop person-centred support strategies and interventions with an aim to optimising positive emotional states throughout the cancer journey. PMID- 27357549 TI - Associations Between Cognitive Function, Schizophrenic Symptoms, and Functional Outcome in Early-onset Schizophrenia With and Without a Familial Burden of Psychosis. AB - OBJECTIVE: The purpose of the present study was to assess the relationship between various domains of cognitive functions, the intensity of psychopathological symptoms, and the general functional outcome in adolescents with early-onset schizophrenia. METHOD: 33 adolescents with early-onset schizophrenia (EOS) were investigated in their partial symptom remission period. The control group consisted of 30 healthy adolescents. Schizophrenia was diagnosed on the basis of ICD-10 criteria. Psychopathological symptoms were assessed with the use of the PANSS (Positive and Negative Symptoms Scale) scale. General functioning was evaluated with the use of the CGAS (Children's Global Assessment Scale) scale. RESULTS: Significant dysfunctions of various aspects of working memory, executive functions, and verbal memory were found in the group of EOS adolescents, as compared to the control group. Working memory and executive function deficits were significantly more severe in patients with a greater intensity of negative schizophrenia symptoms. EOS patients with a familial burden of psychosis presented greater cognitive deficits than patients without such a burden. CONCLUSIONS: These data suggest that visual working memory and verbal memory deficits with a higher intensity of negative and positive symptoms proved to be significant predictors of poor functioning. Limitations of the study are discussed. PMID- 27357550 TI - Identification of Emotional Distress Among Asylum Seekers and Migrant Workers by Primary Care Physicians: A Brief Report. AB - BACKGROUND: Emotional distress (ED) is prevalent among immigrants. The open clinic of Physicians for Human Rights (PHR)-Israel provides free medical and psychiatric treatment to immigrants without access to the ambulatory health service. In 2010, the psychiatric records represented 1% of the total medical files (N=28,000) in the open clinic. OBJECTIVE: To compare service users' self reported ED and its identification by general practitioners (GP) and to identify socio-demographic variables associated with ED. METHOD: A convenience sample (N=97) of the general medical service users completed the 12-item version of the General Health Questionnaire (GHQ-12). A score of 11 or above was considered a suspected mental disorder. The GPs' clinical assessment of ED was compared with the self-reported score. RESULTS: The sample's mean GHQ-12 score was higher than the threshold (M=12.7, SD=6.3, range 0-35). Fifty three percent (n=51) had a GHQ 12 score higher than 11, and 8% (n=8) were identified by the GPs as emotionally distressed and/or in need of psychiatric care. The mean score of the study sample was higher than that found in past studies regarding the Arab-Israeli general population (M=10.8, SD=0.35). Employment was the only socio-demographic variable significantly associated with ED. CONCLUSIONS: ED was high among immigrants, but under-diagnosed by GPs. Employment might serve as a protective factor for ED. PMID- 27357551 TI - Medical Clowning and Psychosis: A Case Report and Theoretical Review. AB - The medical clown has become an accepted therapeutic figure in non-psychiatric hospital departments in recent years. However, the potential role of the clown in psychiatry, especially for the treatment of psychosis, has not been investigated. We report here on the functioning of a medical clown in an inpatient psychiatric department. A program using psychodramatic group therapy techniques with the clown serving as moderator was developed. We describe the case of one individual diagnosed with schizophrenia who in the course of four and a half months of group therapy led by the medical clown was able to adopt a succession of surprising roles. This process may have contributed to the patient's remission. We discuss the special capacity of medical clowns to encourage communication and indulge in fantasy while returning to consensual reality. We suggest that this may have particular relevance in work with psychotic individuals. PMID- 27357552 TI - The Fate of Polish Psychiatry under German Occupation in World War II. AB - Polish psychiatry was since its origin deeply influenced by German (Austrian) and Russian psychiatry. As a larger part of the Polish territory had belonged to Germany or Austria before 1918, many institutions and staff in mental health had a German or Austrian history. During the occupation nearly all mental hospitals were taken over by the Germans, sometimes all the patients, sometimes part of them were murdered, and often the staff members were shot together with their patients. Jews were separated from non-Jews and killed. Some institutions continued to work under German rule and with German directors. This paper will explore these issues from a historical and organizational perspective and address how Polish psychiatry attempted to survive during and after the war. PMID- 27357553 TI - The Effectiveness of Early Group Intervention for Military Reserves Soldiers: The Role of the Repressive Coping Style. AB - This study had two aims: 1. To examine whether soldiers who participated in Early Group Intervention (EGI) would show less distress and better functioning and physical health than soldiers who did not participate in EGI, and 2. To examine the contribution of the intervention to participants with repressive coping style. The sample comprised 166 male reserve soldiers who fought in the Second Lebanon War. The intervention was conducted three months after the traumatic event, was based on military protocol, and took place over the course of one day. Data were collected at two points in time (four months apart). The findings indicated that after EGI, the intervention group experienced less post-traumatic distress than did the control group. In addition, four months after the intervention, the functioning and physical health of the intervention group was significantly better than that of the control group. Notably, the intensity of post-traumatic distress before the intervention was lower among repressors and low-anxious soldiers than among soldiers in the other two groups (high-anxious and defensive). No significant differences were found after the intervention with regard to the various styles of coping with post-traumatic distress. Future clinical implications of the findings are discussed. PMID- 27357554 TI - Cardiovascular Fitness and Neurocognitive Performance among Older Adults in the Maintenance Stage of Cardiac Rehabilitation. AB - BACKGROUND: Cardiovascular fitness is associated with cognition in advanced age. Cardiovascular disease (CVD) is a risk factor for cognitive decline beyond the normal aging process, thus we investigated this association in CVD patients. METHOD: Patients in phase III of cardiac rehabilitation were divided into high and low cardiovascular fitness groups based on their predicted peak VO2. Cognition was assessed by a battery of neuropsychological tests examining memory, attention, visual spatial function, executive function and global cognitive score. RESULTS: The two groups were similar on reported physical activity and on the Mini-Mental State Examination (MMSE). However, the high fitness group had significantly higher scores than the lower fitness group on attention and on the global cognitive score, and marginally significant scores on executive functioning. LIMITATION: Due to the small sample size no differentiation was made among the various CVD conditions. CONCLUSION: Higher cardiovascular fitness of CVD patients is associated with superior cognition - predominantly in attention and executive functioning. PMID- 27357555 TI - Psychiatric Symptoms and Quality of Life in Military Personnel Deployed Abroad. AB - BACKGROUND: Military personnel deployed abroad could be exposed to more risk factors that adversely affect quality of life. In this study, we examined psychiatric symptoms and quality of life in Turkish Armed Forces deployed to Afghanistan. METHOD: A total of 289 Turkish military personnel working in Afghanistan enrolled in this study. They completed two surveys containing questions about socio-demographic characteristics. Data were collected and analyzed from 258 of the participants. RESULTS: The general symptom scores (GSI) were above 1 in 20.8 Percent (n=54) of the participants. The lowest SF-36 scores by the sub-groups were mental health (59.14 +/- 18.56) and vitality (59.25 +/- 21.17). The highest score was in the physical function subscale (84.42 +/- 19.53). All Quality of Life Questionnaire Short Form (SF-36)subscale scores were lower in the GSI above 1 group than the GSI below 1 group. In the GSI above 1 group: education level and depression affected SF-36 physical functioning; paranoid ideation and somatization affected SF-36 role limitations due to physical health; age and somatization affected SF-36 pain; age affected SF-36 general health; phobic anxiety affected SF-36 vitality; age, tenure of occupation, tenure abroad; and phobic anxiety affected SF-36 mental health. CONCLUSIONS: The negative effects of psychiatric symptoms on the quality of life were similar to those in the general population and in specific disease groups. These results should be considered when evaluating the mental health of military personnel deployed abroad. PMID- 27357556 TI - Effectiveness of Aerobic Exercise as an Augmentation Therapy for Inpatients with Major Depressive Disorder: A Preliminary Randomized Controlled Trial. AB - BACKGROUND: Physical exercise has been shown to reduce depressive symptoms when used in combination with antidepressant medication. We report a randomized controlled trial of aerobic exercise compared to stretching as an augmentation strategy for hospitalized patients with major depression. METHODS: Male or female patients, 18-80 years, diagnosed with a Major Depressive Episode, were randomly assigned to three weeks of augmentation therapy with aerobic (n=6) or stretching exercise (n=6). Depression was rated, at several time points using the 21-item Hamilton Depression Scale (HAM-D), Beck Depression Inventory (BDI) and other scales. RESULTS: According to the HAM-D, there were four (out of six) responders in the aerobic group, two of whom achieved remission, and none in the stretching group. According to the BDI, there were two responders in the aerobic group who were also remitters and none in the stretching group. CONCLUSIONS: The results of this small study suggest that aerobic exercise significantly improves treatment outcome when added to antidepressant medication. However, due to the small sample size the results must be regarded as preliminary and further studies are needed to confirm the findings. PMID- 27357557 TI - How Do Meaning in Life and Positive Affect Relate to Adaptation to Stress? The Case of Firefighters Following the Mount Carmel Forest Fire. AB - BACKGROUND: We examined how positive affect (PA) and meaning in life (MIL) conjointly regulate posttraumatic stress disorder (PTSD) symptoms and perceived coping self-efficacy. Hypotheses were guided by a recent holistic model, according to which PA and MIL should compensate for each other in relating to adaptation to high stress. METHOD: The sample included 75 Israeli firefighters who took active part in extinguishing the 2010 Mount Carmel forest fire. RESULTS: PA and MIL helped to compensate for the other, demonstrating that when one of them was low, the other related to higher adaptation. That is, under low MIL, PA related to PTSD symptoms and coping self-efficacy, and under low PA, MIL related to PTSD symptoms and coping self-efficacy. LIMITATION: The study design was cross sectional and therefore precluded any causal inferences. CONCLUSIONS: The findings lend additional support to the holistic model and help to understand how subjective well-being and MIL correlate with adaptation to stress. PMID- 27357558 TI - The Israeli-Polish Mental Health Association: Its History and Activities. AB - The Israeli-Polish Mental Health Association (IPMHA) was founded in 2000. It is a unique organization as it is not only one of the many associations for mental health professionals but also a platform for people from distant countries who share an important and traumatic past. IPMHA members have been engaged in studies of consequences of massive trauma, intergenerational transmission of trauma and help for trauma survivors. Keeping in mind the obligation of mental health professions to contribute to an enlightened and tolerant society, the IPMHA members have been trying to deal with "the past in the present," investigating the roots of the harm caused by racial and ethnic hatred, anti-Semitism and other forms of social prejudice. The IPMHA activities included symposia with discussions facilitated by the use of the dynamic group formula. Some of the materials presented in the meetings were published in Polish professional journals. This article reports on the activities of the IPMHA with special focus on the accompanying emotionally loaded problems. PMID- 27357560 TI - Assessment of collection schemes for packaging and other recyclable waste in European Union-28 Member States and capital cities. AB - The Waste Framework Directive obliged European Union Member States to set up separate collection systems to promote high quality recycling for at least paper, metal, plastic and glass by 2015. As implementation of the requirement varies across European Union Member States, the European Commission contracted BiPRO GmbH/Copenhagen Resource Institute to assess the separate collection schemes in the 28 European Union Member States, focusing on capital cities and on metal, plastic, glass (with packaging as the main source), paper/cardboard and bio waste. The study includes an assessment of the legal framework for, and the practical implementation of, collection systems in the European Union-28 Member States and an in depth-analysis of systems applied in all capital cities. It covers collection systems that collect one or more of the five waste streams separately from residual waste/mixed municipal waste at source (including strict separation, co-mingled systems, door-to-door, bring-point collection and civic amenity sites). A scoreboard including 13 indicators is elaborated in order to measure the performance of the systems with the capture rates as key indicators to identify best performers. Best performance are by the cities of Ljubljana, Helsinki and Tallinn, leading to the key conclusion that door-to-door collection, at least for paper and bio-waste, and the implementation of pay-as-you-throw schemes results in high capture and thus high recycling rates of packaging and other municipal waste. PMID- 27357559 TI - Iron overload by Superparamagnetic Iron Oxide Nanoparticles is a High Risk Factor in Cirrhosis by a Systems Toxicology Assessment. AB - Superparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent have been widely used in magnetic resonance imaging for tumor diagnosis and theranostics. However, there has been safety concern of SPIONs with cirrhosis related to excess iron-induced oxidative stress. In this study, the impact of iron overload by SPIONs was assessed on a mouse cirrhosis model. A single dose of SPION injection at 0.5 or 5 mg Fe/kg in the cirrhosis group induced a septic shock response at 24 h with elevated serum levels of liver and kidney function markers and extended impacts over 14 days including high levels of serum cholesterols and persistent low serum iron level. In contrast, full restoration of liver functions was found in the normal group with the same dosages over time. Analysis with PCR array of the toxicity pathways revealed the high dose of SPIONs induced significant expression changes of a distinct subset of genes in the cirrhosis liver. All these results suggested that excess iron of the high dose of SPIONs might be a risk factor for cirrhosis because of the marked impacts of elevated lipid metabolism, disruption of iron homeostasis and possibly, aggravated loss of liver functions. PMID- 27357561 TI - Financial implications of compliance with EU waste management goals: Feasibility and consequences in a transition country. AB - This paper outlines the approach that can assist decision makers to have first preliminary insights regarding costs of complying with requested European Union municipal waste management goals in transition and developing countries. Serbia, as a joining member of European Union, must confront itself with the challenges resulting from European Union waste management directives. Implementation of waste separation units and the construction of sanitary landfills is already in place in Serbia. However, new waste management practice will need additional transformation and will require implementation of waste treatment technologies for additional management of generated waste. Implementation of analyzed best available technology/techniques for waste treatment can support the country's effort in reaching the policy goals. However, the question here is how much will the implementation of additional waste treatments influence the overall waste management costs? Results of the scenario's financial viability show that composting and sanitary landfill are the most viable solutions regarding the costs, even under increasing discount rates. Although different discount rates influence the overall gate fees and net present values, the level of affordability for different scenarios remains the same. PMID- 27357562 TI - Sustainability assessment and comparison of waste management systems: The Cities of Sofia and Nis case studies. AB - Sustainability assessment of a waste management system is a very complex problem for numerous reasons. Firstly, it is a problem of environmental assessment, economic viability and social acceptability, and also a choice of the most practical waste treatment technique, taking into account all the specific areas in which a waste management system is implemented. For these reasons, among others, it is very important to benchmark, cooperate and exchange experiences in areas with similar characteristics. In this study, a comparison of waste management scenarios in the Cities of Nis and Sofia was performed. Based on the amount and composition of municipal solid waste, and taking into account local specifics (economic conditions, social acceptance, etc.), different scenarios were developed: landfilling without energy recovery, landfilling with energy recovery, mechanical-biological treatment, anaerobic digestion with biogas utilization and incineration with energy recovery. Scenario ranking was done using multi-criteria analysis and 12 indicators were chosen as the criteria. The obtained results show that the most sustainable scenario in both case studies is the mechanical-biological treatment (recycling, composting and Refuse Derived Fuel production). Having in mind that this scenario is the current waste management system in Sofia, these results can help decision-makers in the City of Nis in choosing a successful and sustainable waste management system. PMID- 27357563 TI - Utilization of ferrochrome wastes such as ferrochrome ash and ferrochrome slag in concrete manufacturing. AB - Solid waste management is one of the subjects essentially addressing the current interest today. Due to the scarcity of land filling area, utilization of wastes in the construction sector has become an attractive proposition for disposal. Ferrochrome ash (FA) is a dust obtained as a waste material from the gas cleaning plant of Ferro alloy industries. It possesses the chemical requirements of granulated slag material used for the manufacture of Portland cement. Ferrochrome slag (FS) is another residue that is obtained as a solid waste by the smelting process during the production of stainless steel in Ferroalloy industries. FS possesses the required engineering properties of coarse aggregates. The possibility of using FA with lime for partial replacement of ordinary Portland cement (OPC) and FS for total replacement of natural coarse aggregates is explored in this research. The combined effect of FA with lime and FS-addition on the properties of concrete, such as workability, compressive strength, flexural strength, splitting tensile strength and sorptivity, were studied. Results of investigation revealed improvement in strength and durability properties of concrete on inclusion of FA and FS. Concrete mix containing 40% FA with 7% lime (replacing 47% OPC) and100% of FS (replacing 100% natural coarse aggregate) achieved the properties of normal concrete or even better properties at all ages. The results were confirmed by microscopic study such as X-ray diffraction and petrography examination. Environmental compatibility of concrete containing FA and FS was verified by the toxicity characteristic leaching procedure test. PMID- 27357564 TI - [Depression in androgen-deprivated men with localized prostate cancer]. PMID- 27357565 TI - Molecular epidemiological analysis of three hepatitis C virus outbreaks in Jammu and Kashmir State, India. AB - Outbreaks of hepatitis C virus (HCV) infection are associated with unsafe injection practices, intravenous drug abuse and other exposure to blood and body fluids. We report here three outbreaks of HCV infection from Jammu and Kashmir (J&K) State, India, which occurred over a period of 3 years and in which molecular epidemiological investigations identified a presumptive common source of infection, most likely a single healthcare venue. Representative blood samples collected from cases of hepatitis C were sent to the National Centre for Disease Control (NCDC) for molecular characterization. These samples were positive by HCV ELISA. Subsequently, specimens were also tested for the presence of HCV RNA by RT PCR. Sequencing was carried out for all positive samples. A total of 812 cases were laboratory confirmed by HCV ELISA; a total of 115 samples were sent to the NCDC for RT-PCR, and 77 were positive. Subtype 3a of HCV was found in all samples from Anantnag (February 2013); and for subtype 3b, in all samples from Srinagar (May 2015). Subtypes 3a and 3g were identified from two samples from the Kulgam outbreak (July 2014). A detailed epidemiological investigation should be conducted whenever a cluster of HCV cases is revealed, as this potentially allows for the identification of larger outbreaks. Epidemiological investigations of outbreaks should be further supported by inclusion of molecular tests. Efforts to limit therapeutic injections to only those cases having strong medical/surgical indications and to restrict the use of non-sterile needles are essential to prevent transmission of HCV. PMID- 27357568 TI - Kawasaki disease and giant coronary artery aneurysms: the role of echocardiography from diagnosis through follow-up. AB - Kawasaki disease is an acquired vasculitis that can affect the coronary arteries placing the patient at risk for coronary artery thrombosis, myocardial ischemia and infarction. The risk of complications related to coronary artery involvement persists for years despite recovery from the acute illness phase. The risk of late coronary disease progression necessitates long term follow-up generally accomplished by non-invasive echocardiography in pediatric patients. We review the utility of echocardiography in patients with Kawasaki disease as it relates to initial management, risk stratification and follow-up of these children. PMID- 27357566 TI - Air Pollution Stress and the Aging Phenotype: The Telomere Connection. AB - Aging is a complex physiological phenomenon. The question why some subjects grow old while remaining free from disease whereas others prematurely die remains largely unanswered. We focus here on the role of air pollution in biological aging. Hallmarks of aging can be grouped into three main categories: genomic instability, telomere attrition, and epigenetic alterations leading to altered mitochondrial function and cellular senescence. At birth, the initial telomere length of a person is largely determined by environmental factors. Telomere length shortens with each cell division and exposure to air pollution as well as low residential greens space exposure is associated with shorter telomere length. Recent studies show that the estimated effects of particulate air pollution exposure on the telomere mitochondrial axis of aging may play an important role in chronic health effects of air pollution. The exposome encompasses all exposures over an entire life. As telomeres can be considered as the cellular memories of exposure to oxidative stress and inflammation, telomere maintenance may be a proxy for assessing the "exposome". If telomeres are causally related to the aging phenotype and environmental air pollution is an important determinant of telomere length, this might provide new avenues for future preventive strategies. PMID- 27357567 TI - The Epigenetic Consequences of Paternal Exposure to Environmental Contaminants and Reproductive Toxicants. AB - Human populations are exposed to a wide spectrum of environmental contaminants, some of which are considered reproductive toxins. The influence of such toxins on the male reproductive system has been investigated extensively in animal models, while epidemiological studies seek to understand the effect of human exposures. The basic tenant of epidemiological studies in male human reproduction is to infer how one or more substances alter the hormonal profile, seminal characteristics, or both. Determining if a substance alters semen quality may not always provide the underlying mechanism. The mechanisms by which toxins may alter human sperm and semen quality are typically examined as a function of hormonal changes and cellular damage. The possibility that more subtle epigenetic alterations underlie some of the reproductive changes has, until recently, received little attention. In this review, we discuss the roles of epigenetics in human spermatogenesis, while considering the impact of reproductive toxicants on the epigenome. PMID- 27357571 TI - Generation of liquid crystallinity from a Td-symmetry central unit. AB - A series of new columnar liquid crystals containing an adamantane central unit with its four bridgehead positions partially or fully decorated with different numbers (1-4) of 3,4,5-tris(dodecyloxy)phenyl carbamoyl groups were designed and investigated carefully to explore the structure-property correlations. The molecular structures and mesomorphic properties of the DLCs were characterized by (1)H-NMR, (13)C-NMR, IR, UV-vis, POM, DSC and XRD. It was found that the mesophase symmetry and thermal stability were extremely dependent on the structures of the adamantane derivatives. No mesophase was observed for the 1 adamantanecarboxylic acid derivative ADLC1, while two different mesophases were observed for ADLC2, a 1,3-disubstituted derivative functionalized with two 3,4,5 tris(dodecyloxy)phenyl carbamoyl groups at two symmetric bridgehead positions. At lower temperature ADLC2 exhibited a rectangular columnar phase, which switched to a square columnar phase possessing a wide temperature range. Similarly, a hexagonal columnar mesophase was observed for the bridgehead trisubstituted adamantane molecule ADLC3. Interestingly, the fully bridgehead-functionalized 1,3,5,7-tetrasubstituted adamantane compound ADLC4 completely lost liquid crystallinity. PMID- 27357569 TI - Droplet organelles? AB - Cells contain numerous, molecularly distinct cellular compartments that are not enclosed by lipid bilayers. These compartments are implicated in a wide range of cellular activities, and they have been variously described as bodies, granules, or organelles. Recent evidence suggests that a liquid-liquid phase separation (LLPS) process may drive their formation, possibly justifying the unifying term "droplet organelle". A veritable deluge of recent publications points to the importance of low-complexity proteins and RNA in determining the physical properties of phase-separated structures. Many of the proteins linked to such structures are implicated in human diseases, such as amyotrophic lateral sclerosis (ALS). We provide an overview of the organizational principles that characterize putative "droplet organelles" in healthy and diseased cells, connecting protein biochemistry with cell physiology. PMID- 27357570 TI - Spatial control of lipid droplet proteins by the ERAD ubiquitin ligase Doa10. AB - The endoplasmic reticulum (ER) plays a central role in the biogenesis of most membrane proteins. Among these are proteins localized to the surface of lipid droplets (LDs), fat storage organelles delimited by a phospholipid monolayer. The LD monolayer is often continuous with the membrane of the ER allowing certain membrane proteins to diffuse between the two organelles. In these connected organelles, how some proteins concentrate specifically at the surface of LDs is not known. Here, we show that the ERAD ubiquitin ligase Doa10 controls the levels of some LD proteins. Their degradation is dependent on the localization to the ER and appears independent of the folding state. Moreover, we show that by degrading the ER pool of these LD proteins, ERAD contributes to restrict their localization to LDs. The signals for LD targeting and Doa10-mediated degradation overlap, indicating that these are competing events. This spatial control of protein localization is a novel function of ERAD that might contribute to generate functional diversity in a continuous membrane system. PMID- 27357573 TI - Fake Graduates. AB - There is growing concern regarding the erosion of industries' trust in the reliability and validity of university graduates. Fake graduates are described in this letter. This article endeavors to warn of a new version of the scholarly black market, in which theses and dissertations are sold to students seeking to graduate under false pretenses. PMID- 27357572 TI - A 2.5D Reactive Transport Model for Fracture Alteration Simulation. AB - Understanding fracture alteration resulting from geochemical reactions is critical in predicting fluid migration in the subsurface and is relevant to multiple environmental challenges. Here, we present a novel 2.5D continuum reactive transport model that captures and predicts the spatial pattern of fracture aperture change and the development of an altered layer in the near fracture region. The model considers permeability heterogeneity in the fracture plane and updates fracture apertures and flow fields based on local reactions. It tracks the reaction front of each mineral phase and calculates the thickness of the altered layer. Given this treatment, the model is able to account for the diffusion limitation on reaction rates associated with the altered layer. The model results are in good agreement with an experimental study in which a CO2 acidified brine was injected into a fracture in the Duperow Dolomite, causing dissolution of calcite and dolomite that result in the formation of a preferential flow channel and an altered layer. With an effective diffusion coefficient consistent with the experimentally observed porosity of the altered layer, the model captures the progressive decrease in the dissolution rate of the fast-reacting mineral in the altered layer. PMID- 27357574 TI - Conference Wolves in Sheep's Clothing. AB - In some cases, organizing a conference resembles a high-profit business. Some of these conferences are wolves in sheep's clothing. This article draws readers' attention to current examples of such unethical business conferences. PMID- 27357575 TI - Aristotle and Autism: Reconsidering a Radical Shift to Virtue Ethics in Engineering. AB - Virtue-based approaches to engineering ethics have recently received considerable attention within the field of engineering education. Proponents of virtue ethics in engineering argue that the approach is practically and pedagogically superior to traditional approaches to engineering ethics, including the study of professional codes of ethics and normative theories of behavior. This paper argues that a virtue-based approach, as interpreted in the current literature, is neither practically or pedagogically effective for a significant subpopulation within engineering: engineers with high functioning autism spectrum disorder (ASD). Because the main argument for adopting a character-based approach is that it could be more successfully applied to engineering than traditional rule-based or algorithmic ethical approaches, this oversight is problematic for the proponents of the virtue-based view. Furthermore, without addressing these concerns, the wide adoption of a virtue-based approach to engineering ethics has the potential to isolate individuals with ASD and to devalue their contributions to moral practice. In the end, this paper gestures towards a way of incorporating important insights from virtue ethics in engineering that would be more inclusive of those with ASD. PMID- 27357576 TI - Flavobacterium panacis sp. nov., isolated from rhizosphere of Panax ginseng. AB - A novel bacterial strain, designated DCY106(T), was isolated from soil collected from the rhizosphere of ginseng (Panax ginseng), in Gochang, Republic of Korea. Strain DCY106(T) is Gram-negative, yellow-pigmented, non-flagellate, motile, non spore-forming, rod-shaped, and strictly aerobic. The strain grows optimally at 25 30 degrees C and pH 6.5-7.5. Phylogenetically, strain DCY106(T) is closely related to Flavobacterium arsenitoxidans KCTC 22507(T) (98.41 %), followed by Flavobacterium cutihirudini LMG 26922(T) (97.67 %), Flavobacterium nitrogenifigens LMG 28694(T) (97.59 %), Flexibacter auranticus LMG 3987(T) (97.38 %), Flavobacterium defluvi KCTC 12612(T) (97.21 %) and Flavobacterium chilense LMG 26360(T) (97.05 %). The 16S rRNA gene sequence similarities to all other Flavobacterium species were below 97 %. The DNA G+C content of strain DCY106(T) is 34.2 mol% and the DNA-DNA relatedness between strain DCY106(T) and F. cutihirudini LMG 26922(T), F. auranticus LMG 3987(T), F. defluvi KCTC 12612(T) and F. chilense LMG 26360(T) were below 40.0 %. The menaquinone of the type MK-6 was found to be the predominant respiratory quinone. The major polar lipids were identified as phosphatidylethanolamine, phosphatidylserine, two unidentified aminolipids (APL1, APL6) and one unidentified lipid L2. C15:0, iso-C15:0 and summed feature 3 (iso-C15:0 2OH/C16:1 omega7c) were identified as the major fatty acids present in DCY106(T). The results of physiological and biochemical tests allowed strain DCY106(T) to be differentiated phenotypically from other recognized species belonging to the genus Flavobacterium. Therefore, it is suggested that the newly isolated organism represents a novel species, for which the name Flavobacterium panacis sp. nov. is proposed with the type strain designated as DCY106(T) (= JCM 31468(T)= KCTC 42747(T)). PMID- 27357578 TI - VarI-SIG 2015: methods for personalized medicine - the role of variant interpretation in research and diagnostics. PMID- 27357577 TI - The chain of survival in hypothermic circulatory arrest: encouraging preliminary results when using early identification, risk stratification and extracorporeal rewarming. AB - BACKGROUND: The prognosis in hypothermic cardiac arrest is frequently good despite prolonged period of hypoperfusion and cardiopulmonary resuscitation. Apart from protective effect of hypothermia itself established protocols of treatment and novel rewarming techniques may influence on outcome. The purpose of the study was to assess the outcome of patients with hypothermic circulatory arrest treated by means of arterio-venous extracorporeal membrane oxygenation (ECMO) according to locally elaborated protocol in Severe Accidental Hypothermia Center in Cracow, Poland. METHODS: Prospective observational case-series study - all patients with confirmed hypothermic cardiac arrest consulted with hypothermia coordinator were accepted for extracorporeal rewarming, unless contraindications for ECMO were observed (active bleeding). RESULTS: The study population consisted of 10 patients (7 male, median age 48.5 years). The core temperature measured esophageally was 16.9-28.4 degrees C, median 22 degrees C. On admission 5 patients presented with asystole and 5 with ventricular fibrillation. Duration of circulatory arrest before ECMO implantation was 107 to 345 min (median 156 min). The duration of ECMO support was 1.5 to 91 h (median 22 h). Cardiorespiratory stability and full neurologic recovery was achieved in 7 patients. The duration of mechanical ventilation was 88-437 h (median 177 h) and the length of stay in the ICU was 8-26 days (median 15 days). All survivors had mildly impaired (1 patient, LVEF 40 %) or preserved (6 patients, LVEF 55-65 %) left ventricular systolic function at the time of discharge from ICU. The cause of death of non survivors (three patients) was acute myocarditis, massive retroperitoneal bleeding, and massive gastrointestinal bleeding. DISCUSSION AND CONCLUSIONS: Our data confirm the high survival rate (70 %) and excellent neurologic outcome in hypothermic cardiac arrest. The following key elements seem to impact the final prognosis: the appropriate coordination of the rescue operation, immediate high quality CPR (preferably using mechanical chest compression system) and application of ECMO for rewarming and cardiorespiratory support. PMID- 27357579 TI - The feasibility of community level interventions for pre-eclampsia in South Asia and Sub-Saharan Africa: a mixed-methods design. AB - BACKGROUND: Globally, pre-eclampsia and eclampsia are major contributors to maternal and perinatal mortality; of which the vast majority of deaths occur in less developed countries. In addition, a disproportionate number of morbidities and mortalities occur due to delayed access to health services. The Community Level Interventions for Pre-eclampsia (CLIP) Trial aims to task-shift to community health workers the identification and emergency management of pre eclampsia and eclampsia to improve access and timely care. Literature revealed paucity of published feasibility assessments prior to initiating large-scale community-based interventions. Arguably, well-conducted feasibility studies can provide valuable information about the potential success of clinical trials prior to implementation. Failure to fully understand the study context risks the effective implementation of the intervention and limits the likelihood of post trial scale-up. Therefore, it was imperative to conduct community-level feasibility assessments for a trial of this magnitude. METHODS: A mixed methods design guided by normalization process theory was used for this study in Nigeria, Mozambique, Pakistan, and India to explore enabling and impeding factors for the CLIP Trial implementation. Qualitative data were collected through participant observation, document review, focus group discussion and in-depth interviews with diverse groups of community members, key informants at community level, healthcare providers, and policy makers. Quantitative data were collected through health facility assessments, self-administered community health worker surveys, and household demographic and health surveillance. RESULTS: Refer to CLIP Trial feasibility publications in the current and/or forthcoming supplement. CONCLUSIONS: Feasibility assessments for community level interventions, particularly those involving task-shifting across diverse regions, require an appropriate theoretical framework and careful selection of research methods. The use of qualitative and quantitative methods increased the data richness to better understand the community contexts. TRIAL REGISTRATION: NCT01911494. PMID- 27357580 TI - Efficient genomic prediction based on whole-genome sequence data using split-and merge Bayesian variable selection. AB - BACKGROUND: Use of whole-genome sequence data is expected to increase persistency of genomic prediction across generations and breeds but affects model performance and requires increased computing time. In this study, we investigated whether the split-and-merge Bayesian stochastic search variable selection (BSSVS) model could overcome these issues. BSSVS is performed first on subsets of sequence-based variants and then on a merged dataset containing variants selected in the first step. RESULTS: We used a dataset that included 4,154,064 variants after editing and de-regressed proofs for 3415 reference and 2138 validation bulls for somatic cell score, protein yield and interval first to last insemination. In the first step, BSSVS was performed on 106 subsets each containing ~39,189 variants. In the second step, 1060 up to 472,492 variants, selected from the first step, were included to estimate the accuracy of genomic prediction. Accuracies were at best equal to those achieved with the commonly used Bovine 50k-SNP chip, although the number of variants within a few well-known quantitative trait loci regions was considerably enriched. When variant selection and the final genomic prediction were performed on the same data, predictions were biased. Predictions computed as the average of the predictions computed for each subset achieved the highest accuracies, i.e. 0.5 to 1.1 % higher than the accuracies obtained with the 50k SNP chip, and yielded the least biased predictions. Finally, the accuracy of genomic predictions obtained when all sequence-based variants were included was similar or up to 1.4 % lower compared to that based on the average predictions across the subsets. By applying parallelization, the split-and-merge procedure was completed in 5 days, while the standard analysis including all sequence-based variants took more than three months. CONCLUSIONS: The split-and-merge approach splits one large computational task into many much smaller ones, which allows the use of parallel processing and thus efficient genomic prediction based on whole genome sequence data. The split-and-merge approach did not improve prediction accuracy, probably because we used data on a single breed for which relationships between individuals were high. Nevertheless, the split-and-merge approach may have potential for applications on data from multiple breeds. PMID- 27357581 TI - Further Exploring the Link Between Religion and Existential Health: The Effects of Religiosity and Trait Differences in Mentalizing on Indicators of Meaning in Life. AB - Religiosity contributes to perceptions of meaning. One of the cognitive foundations for religious belief is the capacity to mentalize the thoughts, emotions, and intentions of others (Theory of Mind). We examined how religiosity and trait differences in mentalizing interact to influence meaning. We hypothesized that people who are most cognitively inclined toward religion (high mentalizers) receive the greatest existential benefits (i.e., high and secure meaning) from religiosity. We assessed individual differences in mentalizing and religiosity, and measured indicators of meaning. Results confirmed that the combination of high mentalizing and high religiosity corresponded to the highest levels of existential health. PMID- 27357582 TI - Patient Autonomy in Talmudic Context: The Patient's "I Must Eat" on Yom Kippur in the Light of Contemporary Bioethics. AB - In contemporary bioethics, the autonomy of the patient has assumed considerable importance. Progressing from a more limited notion of informed consent, shared decision making calls upon patients to voice the desires and preferences of their authentic self, engaging in choice among alternatives as a way to exercise deeply held values. One influential opinion in Jewish bioethics holds that Jewish law, in contradistinction to secular bioethics, limits the patient's exercise of autonomy only in those instances in which treatment choices are sensitive to preferences. Here, we analyze a discussion in the Mishna, a foundational text of rabbinic Judaism, regarding patient autonomy in the setting of religiously mandated fasting, and commentaries in the Babylonian and Palestinian Talmuds, finding both a more expansive notion of such autonomy and a potential metaphysical grounding for it in the importance of patient self-knowledge. PMID- 27357583 TI - Thin-plate spline analysis of mandibular shape changes induced by functional appliances in Class II malocclusion : A long-term evaluation. AB - AIMS: The purpose of this work was to evaluate the long-term morphological mandibular changes induced by functional treatment of Class II malocclusion with mandibular retrusion. METHODS: Forty patients (20 females, 20 males) with Class II malocclusion consecutively treated with either a Bionator or an Activator followed by fixed appliances were compared with a control group of 40 subjects (19 females, 21 males) with untreated Class II malocclusion. Lateral cephalograms were available at the start of treatment (T1, mean age 9.9 years), at the end of treatment with functional appliances (T2, mean age 12.2 years), and for long-term follow-up (T3, mean age 18.3 years). Mandibular shape changes were analyzed on lateral cephalograms of the subjects in both groups via thin-plate spline (TPS) analysis. Shape differences were statistically analyzed by conducting permutation tests on Goodall F statistics. RESULTS: In the long term, both the treated and control groups exhibited significant longitudinal mandibular shape changes characterized by upward and forward dislocation of point Co associated with a vertical extension in the gonial region and backward dislocation of point B. CONCLUSION: Functional appliances induced mandible's significant posterior morphogenetic rotation over the short term. The treated and control groups demonstrated similar mandibular shape over the long term. PMID- 27357584 TI - Correlation between condylar position and different sagittal skeletal facial types. AB - OBJECTIVE: Condylar position may play a key role in the stability of orthodontic treatment of patients presenting with different skeletal patterns. The aim of the present study was to assess via cone beam computed tomography (CBCT) correlations between condylar position and sagittal skeletal relationship. PATIENTS AND METHODS: Condylar positions in CBCT images of 20 patients presenting with a Class I skeletal pattern, 20 with a Class II skeletal pattern, and 20 with a Class III skeletal pattern were evaluated retrospectively. The chi (2) test was used to assess the correlation between condylar position and sagittal skeletal relationships. RESULTS: The condyles were anteriorly positioned in patients with Class II skeletal pattern in comparison with those with Class I and III skeletal patterns. No significant differences in condylar position between Class I and Class III subjects were detected. CONCLUSION: A significant correlation between condylar position and sagittal skeletal patterns was observed in the present study. This relationship should be considered when planning and carrying out the appropriate orthodontic treatment for temporomandibular anomalies. PMID- 27357585 TI - A molecular study of the genus Spelaeomyia (Diptera: Phlebotominae) with description of the male of Spelaeomyia moucheti. AB - BACKGROUND: The genus Spelaeomyia includes four African species considered as being cavernicolous: Spelaeomyia darlingi, Spelaeomyia mirabilis, Spelaeomyia emilii and Spelaeomyia moucheti. Despite a potential role in Leishmania major leishmaniasis transmission in Mali, no molecular studies and only few morphological studies have addressed relationships between species of Spelaeomyia. METHODS: Specimens of Sa. moucheti were collected in two different sites in Gabon. Spelaeomyia emilii and Sa. darlingi specimens came from Gabon and Mali. Specimens of Sa. mirabilis were collected in the Democratic Republic of Congo and Gabon. All specimens were caught using CDC miniature light traps, then dissected, both heads and genitalia were kept for morphological analysis and the rest of the bodies were kept for molecular processing and analyses. RESULTS: Some unidentified males are associated to Sa. moucheti females using molecular tools and are described for the first time. A new morphological feature is observed on the spermathecae of the female and new drawings are provided. For the first time a phylogenetic analysis is carried out on rDNA and mtDNA markers and it shows that Sa. moucheti is the sister species of Sa. mirabilis. CONCLUSIONS: Spelaeomyia moucheti is the sister species of Sa. mirabilis. This result is in agreement with the sharing of morphological characters between these closely related species. Moreover, these two species are not as cavernicolous as literature previously indicated. They were caught in open rainforest in Gabon. PMID- 27357586 TI - The Perils of Integrating Wellness and Safety and Health and the Possibility of a Worker-Oriented Alternative. AB - In response to the article by Michael B. Lax, MD entitled "The perils of integrating wellness and safety and health and the possibility of a worker oriented alternative," the National Institute for Occupational Safety and Health (NIOSH) provides updated information on the current focus and priorities and addresses concerns raised regarding the Total Worker Health(r) initiative. Many of the concerns and criticisms in the report echo those NIOSH publicly shares on a regular basis. The theory and practice of Total Worker Health (TWH) continues to evolve in response to valuable stakeholder input like that provided by Dr. Lax. In 2015, NIOSH updated the TWH concept to emphasize the main focus of TWH is the primacy of traditional health protection which prioritizes employer responsibilities for the organization of work over individual worker health behaviors. NIOSH acknowledges the past lack of "fit" between theory and practice in some publications of TWH-funded grantees as Dr. Lax points out. NIOSH is hopeful that the solicitation of new research, which is now underway, will clarify the work-centered priorities for TWH-funded research. Based on input from Dr. Lax and other stakeholders, NIOSH looks forward to contributing more effectively to protecting and promoting worker safety and health in the new twenty-first century world of work. PMID- 27357587 TI - Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae in children with acute bacterial meningitis in Mozambique: implications for a national immunization strategy. AB - BACKGROUND: S. pneumoniae is the leading cause of acute bacterial meningitis (ABM) in children. Vaccination using the 10-valent conjugate vaccine (PCV-10) was recently introduced into the National Immunization Program in Mozambique, but data on serotype coverage of this vaccine formulation are scarce. In this study, we investigated the serotype distribution and antimicrobial resistance of isolates of S. pneumoniae causing ABM in children < 5 years at the two largest hospitals in Mozambique. METHODS: Between March 2013 and March 2014, a total of 352 cerebrospinal fluid (CSF) samples were collected from eligible children, of which 119 (33.8 %) were positive for S. pneumoniae. Of these, only 50 samples met the criteria for serotyping and were subsequently serotyped using sequential multiplex PCR (SM-PCR), but 15 samples were non-typable. RESULTS: The most common serotypes of S. pneumoniae were 1 (18.2 %), 5 (15.2 %), 14 (12.1 %), 9 V (12.1 %), 23 F (9.1 %), 6A (9.1 %), 4 (9.1 %) and 6B (6.1 %). Serotypes 1, 5, 9 V, 6A and 12 were mostly prevalent in Northern Mozambique, while serotypes 23 F, 4, 6B, 3 and 15B were predominant in Southern. Serotype coverage of PCV-10 and PCV-13 vaccine formulations were 81.8 % and 93.9 %, respectively. Serotypes 1, 3, 4, 6B, 14, 23 F were resistant to penicillin and sensitive to ceftriaxone. CONCLUSIONS: Our findings shows that changing the current in use PCV-10 vaccine formulation to PCV-13 formulation might increase substantially the protection against invasive strains of S. pneumoniae as the PCV-10 vaccine formulation does not cover the serotypes 3 and 6A, which are prevalent in Mozambique. PMID- 27357588 TI - The Effects of Rheum palmatum L. on the Pharmacokinetic of Major Diterpene Alkaloids of Aconitum carmichaelii Debx. in Rats. AB - BACKGROUND AND OBJECTIVES: Aconitum carmichaelii Debx. (Fuzi) is usually compatible with Rheum palmatum L. (Dahuang) in clinic. The study is conducted to investigate the influence of Dahuang on the pharmacokinetics of Fuzi. METHODS: Twelve rats were randomly divided into two groups. Fuzi group was orally administered a single dose of 38.4 mg/kg total alkaloids from Fuzi, and Fuzi Dahuang group was given 38.4 mg/kg total alkaloids from Fuzi and 76.8 mg/kg Dahuang anthraquinones at the same time. The plasma concentrations of aconitine (AC), mesaconitine (MC), and hypaconitine (HC), benzoylaconine (BAC), benzoylmesaconine (BMC), benzoylhypaconine (BHC), and aconine (ACN) were determined by ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry method. The pharmacokinetic parameters were calculated including maximum plasma concentration (C max), area under the plasma concentration-time curve in all time-points (AUClast), apparent volume of distribution (V z/F), apparent plasma clearance (CL/F), elimination half-life (T 1/2), and time to achieve maximum concentration (T max). RESULTS: AUClast of diester diterpene alkaloids (DDAs) were 58.20, 169.78, 278.48 ng.h/mL for AC, MC, and HC in Fuzi-Dahuang group which were remarkably lower than that in Fuzi group (71.62, 183.13, 410.59 ng.h/mL for AC, MC, HC). CL/F was significantly increased from 173.88 to 218.85 mL/h for AC, 433.22 to 800.21 mL/h for MC, 1150.61 to 1307.30 mL/h for HC after combination. However, with the significantly increased C max, AUClast of monoester diterpene alkaloids (MDAs) and amine diterpenoid alkaloids (ADAs) were 152.42, 1238.95, 287.96, 123.33 ng.h/mL for BAC, BHC, BMC, ACN in Fuzi-Dahuang group which were remarkably higher than that in Fuzi group (54.47, 1105.48, 200.75, 86.48 ng.h/mL for BAC, BHC, BMC, ACN). At the same time, CL/F was significantly decreased from 1030.15 to 607.09, 3594.06 to 1437.54, 1441.23 to 1310.14, and 391.30 to 239.50 mL/h for each one after combination. CONCLUSIONS: Fuzi diterpene alkaloids pharmacokinetics was greatly influenced by Dahuang which may account for the compatibility mechanism of effect-enhancing and toxicity-reducing. PMID- 27357589 TI - [New oral anticoagulants for prophylaxis of stroke : Results of an expert conference on practical use in geriatric patients]. PMID- 27357590 TI - Sudden death after major head and neck cancer surgery due to undetected arrhythmogenic right ventricle cardiomyopathy (ARVC). AB - BACKGROUND: Oral squamous cell carcinoma is the sixth most frequent malignancy in Austria. The incidence of arrhythmogenic right ventricle dysplasia (ARVC), an important cause of sudden cardiac death, is estimated at 1:5000 to 1:1000. CASE REPORT: We present a case of a 75-year-old woman who underwent major oncologic surgery for T4aN0M0 maxillary squamous cell carcinoma and reconstruction with a scapular-latissimus dorsi microvascular flap. The patient died suddenly during her postoperative care. Autopsy revealed pericardiac tamponade due to rupture of the right ventricular wall. Histologic examination showed ARVC in a sample taken directly from the ruptured area. Cause of death was secondary arrhythmia originating from the ARVC. The arrhythmia had led to rupture of the right ventricular wall and sudden cardiac death. DISCUSSION: As per our current knowledge, no cases of maxillary cancer and ARVC as co-morbidities have been reported in the literature. The patient had been given anti-arrhythmia treatment for previously detected atrial fibrillation, which could have been why the arrhythmia was not apparent on the electrocardiogram. Thus, although the appropriate preoperative diagnostics were performed according to current oncologic and anesthesiology guidelines, the potentially lethal cardiac condition of the patient could not be detected. PMID- 27357591 TI - Correlation Between Aquaporin 4 Expression and Different DWI Parameters in Grade I Meningioma. AB - PURPOSE: Diffusion-weighted imaging (DWI) measures water diffusion in biological tissues. Cellular water transport depends on aquaporins (AQPs). The expression of aquaporins might differ in several pathologic disorders. Therefore, the aim of this study was to evaluate the associations between AQP4 expression and different DWI parameters in meningioma. PROCEDURES: Twenty-three patients with meningioma grade I were included in this retrospective study. DWI was obtained with three b values (0; 500; 1000) using a 1.5-T device. ADCmean, ADCmin, ADCmax, and true diffusion coefficients (D) were obtained in every patient. Aquaporin 4 expression was quantified immunohistochemically in four immunoreactivity levels. RESULTS: The estimated DWI parameters (mean value +/- standard deviation, 10-3 mm2 s-1) of the tumors were as follows: ADCmin 0.67 +/- 0.16, ADCmean 0.94 +/- 0.23, ADCmax 1.29 +/- 0.50, and D 0.65 +/- 0.23. The mean level of the AQP4 expression was 2.02 +/- 0.75 points. A statistically significant correlation between AQP4 expression and ADCmax was identified (r = 0.508, p = 0.013). No significant correlations between AQP4 and other DWI parameters were found. CONCLUSIONS: A clear correlation between AQP4 expression and ADCmax values in grade I meningioma was identified. There were no significant correlations between AQP4 expression and other DWI parameters, such as ADCmin, ADCmean, and D. PMID- 27357592 TI - A 23-dB bismuth-doped optical fiber amplifier for a 1700-nm band. AB - It is now almost twenty-five years since the first Erbium-Doped Fiber Amplifier (EDFA) was demonstrated. Currently, the EDFA is one of the most important elements widely used in different kinds of fiber-optic communication systems. However, driven by a constantly increasing demand, the network traffic, growing exponentially over decades, will lead to the overload of these systems ("capacity crunch") because the operation of the EDFA is limited to a spectral region of 1530-1610 nm. It will require a search for new technologies and, in this respect, the development of optical amplifiers for new spectral regions can be a promising approach. Most of fiber-optic amplifiers are created using rare-earth-doped materials. As a result, wide bands in shorter (1150-1530 nm) and longer wavelength (1600-1750 nm) regions with respect to the gain band of Er-doped fibers are still uncovered. Here we report on the development of a novel fiber amplifier operating in a spectral region of 1640-1770 nm pumped by commercially available laser diodes at 1550 nm. This amplifier was realized using bismuth doped high-germania silicate fibers fabricated by MCVD technique. PMID- 27357593 TI - Epoxy composite dusts with and without carbon nanotubes cause similar pulmonary responses, but differences in liver histology in mice following pulmonary deposition. AB - BACKGROUND: The toxicity of dusts from mechanical abrasion of multi-walled carbon nanotube (CNT) epoxy nanocomposites is unknown. We compared the toxic effects of dusts generated by sanding of epoxy composites with and without CNT. The used CNT type was included for comparison. METHODS: Mice received a single intratracheal instillation of 18, 54 and 162 MUg of CNT or 54, 162 and 486 MUg of the sanding dust from epoxy composite with and without CNT. DNA damage in lung and liver, lung inflammation and liver histology were evaluated 1, 3 and 28 days after intratracheal instillation. Furthermore, the mRNA expression of interleukin 6 and heme oxygenase 1 was measured in the lungs and serum amyloid A1 in the liver. Printex 90 carbon black was included as a reference particle. RESULTS: Pulmonary exposure to CNT and all dusts obtained by sanding epoxy composite boards resulted in recruitment of inflammatory cells into lung lumen: On day 1 after instillation these cells were primarily neutrophils but on day 3, eosinophils contributed significantly to the cell population. There were still increased numbers of neutrophils 28 days after intratracheal instillation of the highest dose of the epoxy dusts. Both CNT and epoxy dusts induced DNA damage in lung tissue up to 3 days after intratracheal instillation but not in liver tissue. There was no additive effect of adding CNT to epoxy resins for any of the pulmonary endpoints. In livers of mice instilled with CNT and epoxy dust with CNTs inflammatory and necrotic histological changes were observed, however, not in mice instilled with epoxy dust without CNT. CONCLUSIONS: Pulmonary deposition of epoxy dusts with and without CNT induced inflammation and DNA damage in lung tissue. There was no additive effect of adding CNT to epoxies for any of the pulmonary endpoints. However, hepatic inflammatory and necrotic histopathological changes were seen in mice instilled with sanding dust from CNT-containing epoxy but not in mice instilled with reference epoxy. PMID- 27357594 TI - Systems level analysis of the Chlamydomonas reinhardtii metabolic network reveals variability in evolutionary co-conservation. AB - Metabolic networks, which are mathematical representations of organismal metabolism, are reconstructed to provide computational platforms to guide metabolic engineering experiments and explore fundamental questions on metabolism. Systems level analyses, such as interrogation of phylogenetic relationships within the network, can provide further guidance on the modification of metabolic circuitries. Chlamydomonas reinhardtii, a biofuel relevant green alga that has retained key genes with plant, animal, and protist affinities, serves as an ideal model organism to investigate the interplay between gene function and phylogenetic affinities at multiple organizational levels. Here, using detailed topological and functional analyses, coupled with transcriptomics studies on a metabolic network that we have reconstructed for C. reinhardtii, we show that network connectivity has a significant concordance with the co-conservation of genes; however, a distinction between topological and functional relationships is observable within the network. Dynamic and static modes of co-conservation were defined and observed in a subset of gene-pairs across the network topologically. In contrast, genes with predicted synthetic interactions, or genes involved in coupled reactions, show significant enrichment for both shorter and longer phylogenetic distances. Based on our results, we propose that the metabolic network of C. reinhardtii is assembled with an architecture to minimize phylogenetic profile distances topologically, while it includes an expansion of such distances for functionally interacting genes. This arrangement may increase the robustness of C. reinhardtii's network in dealing with varied environmental challenges that the species may face. The defined evolutionary constraints within the network, which identify important pairings of genes in metabolism, may offer guidance on synthetic biology approaches to optimize the production of desirable metabolites. PMID- 27357595 TI - Shear Piezoelectricity in Poly(vinylidenefluoride-co-trifluoroethylene): Full Piezotensor Coefficients by Molecular Modeling, Biaxial Transverse Response, and Use in Suspended Energy-Harvesting Nanostructures. AB - The intrinsic flexible character of polymeric materials causes remarkable strain deformations along directions perpendicular to the applied stress. The biaxial response in the shear piezoelectricity of polyvinylidenefluoride copolymers is analyzed and their full piezoelectric tensors are provided. The microscopic shear is exploited in single suspended nanowires bent by localized loading to couple flexural deformation and transverse piezoelectric response. PMID- 27357596 TI - Novel Colloidal MoS2 Quantum Dot Heterojunctions on Silicon Platforms for Multifunctional Optoelectronic Devices. AB - Silicon compatible wafer scale MoS2 heterojunctions are reported for the first time using colloidal quantum dots. Size dependent direct band gap emission of MoS2 dots are presented at room temperature. The temporal stability and decay dynamics of excited charge carriers in MoS2 quantum dots have been studied using time correlated single photon counting spectroscopy technique. Fabricated n MoS2/p-Si 0D/3D heterojunctions exhibiting excellent rectification behavior have been studied for light emission in the forward bias and photodetection in the reverse bias. The electroluminescences with white light emission spectra in the range of 450-800 nm are found to be stable in the temperature range of 10-350 K. Size dependent spectral responsivity and detectivity of the heterojunction devices have been studied. The peak responsivity and detectivity of the fabricated heterojunction detector are estimated to be ~0.85 A/W and ~8 * 10(11) Jones, respectively at an applied bias of -2 V for MoS2 QDs of 2 nm mean diameter. The above values are found to be superior to the reported results on large area photodetector devices fabricated using two dimensional materials. PMID- 27357597 TI - Evidence of Aujeszky's disease in wild boar in Serbia. AB - BACKGROUND: Aujeszky's disease is a viral disease of suids caused by Suid Herpesvirus 1. The disease has worldwide distribution with significant economic impact. In Serbia, there is neither an Aujeszky's disease eradication nor national vaccination programme of domestic pigs. Since clinical symptoms of Aujeszky's disease are not specific, it is important to establish a link between clinical signs and presence of ADV active infection in wild boars. The aim of this study was to investigate the possibility of active infection within wild boar showing signs of ADV and also to examine relationship between isolates from domestic pigs and wild boar. Having in mind that virus has not been previously isolated from wild boars in Serbia, we report the first isolation of Suid Herpesvirus 1 from this species in Serbia. RESULTS: Tissue and serum samples from 40 wild boars from eastern Serbia were examined for evidence of Aujeszky's disease (AD). Suid Herpesvirus 1 (SHV1), the cause of AD was isolated on PK15 cell line from three tissue samples, inducing cytopathic effect (CPE) with syncytia forming, and viral genome was detected by polymerase chain reaction (PCR) in eight samples. Genetic analysis of us4, us9 and ul49.5 partial sequences showed high homology between ADV isolates from wild boars and between isolates from wild boars and domestic animals. Neutralizing antibodies were not detected by virus neutralisation test (VNT) in sera from four out of eight PCR positive wild boars suggesting recent infection in those animals. CONCLUSIONS: This is the first demonstration of Aujeszky's disease virus (ADV) in the wild boar population in Serbia although seroconversion has been detected previously. PMID- 27357598 TI - Durability of the virological response after lamivudine discontinuation in lamivudine-resistant patients with a complete virological response after lamivudine and adefovir combination therapy. AB - We investigated the durability of virological response after lamivudine (LAM) discontinuation in LAM-resistant chronic hepatitis B (CHB) patients with complete virological response after LAM-adefovir (ADV) combination therapy. We enrolled 58 patients switched to ADV monotherapy with undetectable viral loads (<12 IU/ml) and normal alanine aminotransferase levels after ADV add-on combination treatment for at least 6 months in LAM-resistant CHB patients. Virologic relapse was defined as HBV DNA detection at more than 20 IU/ml by quantitative polymerase chain reaction determined on two consecutive measurements. During median 40.9 months of follow-up (range 11.5-79.0 months), seven (12.1%) patients experienced virological relapse. The cumulative rate of virological relapse at 3 and 5 years was 5.5% and 22.4%, respectively. Two patients had elevated alanine aminotransferase during virological relapse. These seven patients with virological relapse had undetectable HBV DNA after switching to tenofovir therapy. In our study, switching to ADV monotherapy resulted in sustained HBV DNA suppression in 87.9% of the patients during median 40.9 months follow-up. This adapting step-down strategy, switching from combination therapy to monotherapy in virologically suppressed CHB patients with stable liver disease, may reduce the cost burden and the risk of potentially harmful effects of combination therapy. J. Med. Virol. 89:85-90, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27357599 TI - Major dietary patterns in relation to demographic and socio-economic status and food insecurity in two Iranian ethnic groups living in Urmia, Iran. AB - OBJECTIVE: To identify major dietary patterns and their association with socio economic status (SES) and food insecurity in two major ethnic groups living in Urmia, north-west Iran. DESIGN: A cross-sectional study. SETTING: All four geographical zones of Urmia city. SUBJECTS: Participants (n 723; 427 women and 296 men), aged 20-64 years, from two ethnic groups (445 Azeri Turks and 278 Kurds). RESULTS: Three major dietary patterns were extracted: 'Traditional High SES' (THS), 'Traditional Low SES' (TLS) and 'Transitional'. After adjusting for confounders, the THS pattern was positively associated with education level and negatively associated with moderate or severe food insecurity in Azeri Turks; whereas, among Kurds, it was more common in women and positively associated with age. The TLS pattern was more common among men and negatively associated with educational level and all levels of food insecurity in Azeris; while, among Kurds, it was more common among men, positively associated with being married and negatively associated with household income/capita. The 'Transitional' pattern was positively associated with being employed and negatively associated with age and all levels of food insecurity in Azeris; while, among Kurds, it was more common among men and negatively associated with age, being married and physical activity level. CONCLUSIONS: Findings suggest that household SES and food insecurity are associated with detrimental dietary patterns and that this effect may be stronger than cultural and ethnic background. These patterns differ by age and gender. Therefore, such characteristics should be considered in planning and formulating diet-related policies and programmes. PMID- 27357600 TI - Microdermabrasion: a clinical, histometric, and histopathologic study. AB - BACKGROUND: Microdermabrasion is a nonchemical superficial resurfacing procedure that removes the stratum corneum. Because it is a somewhat subtle procedure, it may be difficult to demonstrate its cosmetic benefit. OBJECTIVES: To assess the efficacy of microdermabrasion in treatment of melasma, postacne scarring, striae distensae, and photoaging by a series of microdermabrasion sittings through clinical, histometric, and histopathologic analysis. PATIENTS AND METHODS: The study was conducted on 38 patients constituting four groups (melasma, acne scars, striae destinsae, and photoaging), each patient was subjected to a series of 8 microdermabrasion treatments performed at 1-week interval. Punch biopsies, at base line, 1 week after the 4th and the 8th session, were obtained from each subject for histometric and histopathologic analysis. RESULTS: Clinically, the improvement in melasma, acne scars, and striae distensae groups was mainly mild to moderate, while in photoaging group was mainly mild. Histometric analysis of epidermal thickness showed insignificant changes in all groups. Histopathologically, decreased melanization and regular distribution of melanosomes in the epidermis were noted in melasma group while increased density of collagen fibers with more regular arrangement in collagen bundles was detected in all candidates of acne scars, striae distensae, and photoaging groups. Meanwhile, Orcein stain did not show any significant changes in elastic fibers. CONCLUSIONS: Microdermabrasion is an easy and safe technique. In this study, most cases showed mild to moderate improvement. Decreased melanization with regular distribution of melanosomes and increased collagen density with regular arrangement of collagen bundles were the most common observed histologic changes. PMID- 27357601 TI - Treatment of eosinophilic cellulitis (Wells syndrome) - a systematic review. AB - Eosinophilic cellulitis (Wells syndrome) is a rare inflammatory skin disease defined by erythematous, tender, sometimes urticarial plaques, possibly with vesicles and bullae, and granulomatous eosinophilic infiltrates in the dermis. Usually the disease has a benign course with spontaneous remission within a few weeks. Nevertheless, recurrences are quite frequent and may occur for several years. The objective of this study was to review the so far reported treatment options for Wells syndrome in a systematic manner. This systematic review is based on a search on Medline, Embase and Cochrane Central Register for English and German articles from 1970 to 2015. Advices on the treatment of Wells syndrome are limited predominately to case reports or to small case series. There are no randomized controlled trials, and control groups are missing. A variety of treatment options for Wells syndrome were reported including topical and systemic corticosteroids, antihistamines, cyclosporine, dapsone, azathioprine, griseofulvin, doxycycline, minocycline, antimalarial medications, oral tacrolimus/topical tacrolimus, sulfasalazine, interferon alpha and gamma, TNF alpha inhibitors, colchicine and PUVA therapy. As well-designed, randomized controlled trials are missing, no guidelines for the treatment of this disease can be given. Due to the small number of patients and the frequent misdiagnosis of this clinical entity, the aim of this systematic overview is to call attention to this rare condition and to help clinicians to diagnose and treat Wells syndrome effectively. Due to the good prognosis and tendency to resolve, systemic treatment should be limited to cases resistant to local therapy or with widespread lesions. PMID- 27357602 TI - Cumulative dosages of antipsychotic drugs are associated with increased mortality rate in patients with Alzheimer's dementia. AB - OBJECTIVE: We wished to investigate the effects of cumulative dosages of antipsychotic drug in Alzheimer's dementia, when controlling for known risk factors, including current antipsychotic exposure, on all-cause mortality. METHOD: We utilized a nationwide, population-based, retrospective cohort study design with mortality as outcome in individual patients diagnosed with Alzheimer's dementia. RESULTS: We included a total of 45 894 patients and followed them for 3 803 996 person-years in total, presenting 27 894 deaths in the study population. Cumulative antipsychotic exposure increased mortality: more than 0 Daily Defined Dosage (DDDs) but less than 90: HR 2.20, 95% CI (2.14-2.27), P < 0.001; more than or equal to 90 DDDs but less than 365: HR 1.81, 95% CI (1.74 1.89), P < 0.001; more than or equal to 365 DDDs but less than 730: HR 1.38, 95% CI (1.428-1.49), P < 0.001; and more than or equal to 730 DDDs: HR 1.06, 95% CI (0.95-1.18), P = 0.322, when controlling for proxy markers of severity, somatic and mental comorbid disorders. CONCLUSION: In this nationwide cohort study of 45 894 patients diagnosed with Alzheimer's dementia, we found that cumulative dosages of antipsychotic drugs were associated with increased mortality rates. PMID- 27357603 TI - Targeting Programmed Cell Death Using Small-Molecule Compounds to Improve Potential Cancer Therapy. AB - Evasion of cell death is one of the hallmarks of cancer cells, beginning with long-established apoptosis and extending to other new forms of cell death. An elaboration of cell death pathways thus will contribute to a better understanding of cancer pathogenesis and therapeutics. With the recent substantial biochemical and genetic explorations of cell death subroutines, their classification has switched from primarily morphological to more molecular definitions. According to their measurable biochemical features and intricate mechanisms, cell death subroutines can be divided into apoptosis, autophagic cell death, mitotic catastrophe, necroptosis, parthanatos, ferroptosis, pyroptosis, pyronecrosis, anoikis, cornification, entosis, and NETosis. Supportive evidence has gradually revealed the prime molecular mechanisms of each subroutine and thus providing series of possible targets in cancer therapy, while the intricate relationships between different cell death subroutines still remain to be clarified. Over the past decades, cancer drug discovery has significantly benefited from the use of small-molecule compounds to target classical modalities of cell death such as apoptosis, while newly identified cell death subroutines has also emerging their potential for cancer drug discovery in recent years. In this review, we comprehensively focus on summarizing 12 cell death subroutines and discussing their corresponding small-molecule compounds in potential cancer therapy. Together, these inspiring findings may provide more evidence to fill in the gaps between cell death subroutines and small-molecule compounds to better develop novel cancer therapeutic strategies. PMID- 27357604 TI - Janus Membranes: Exploring Duality for Advanced Separation. AB - Janus membranes are an emerging class of materials having opposing properties at an interface. This structure results in selective and often novel transport characteristics. In this Minireview, a definition of the Janus membrane, beyond merely asymmetric materials, is introduced and common fabrication strategies are outlined. Also presented are current and potential applications in directional transport, switchable permeation, and performance optimization with detailed mechanisms. PMID- 27357605 TI - Real-time observations of lithium battery reactions-operando neutron diffraction analysis during practical operation. AB - Among the energy storage devices for applications in electric vehicles and stationary uses, lithium batteries typically deliver high performance. However, there is still a missing link between the engineering developments for large scale batteries and the fundamental science of each battery component. Elucidating reaction mechanisms under practical operation is crucial for future battery technology. Here, we report an operando diffraction technique that uses high-intensity neutrons to detect reactions in non-equilibrium states driven by high-current operation in commercial 18650 cells. The experimental system comprising a time-of-flight diffractometer with automated Rietveld analysis was developed to collect and analyse diffraction data produced by sequential charge and discharge processes. Furthermore, observations under high current drain revealed inhomogeneous reactions, a structural relaxation after discharge, and a shift in the lithium concentration ranges with cycling in the electrode matrix. The technique provides valuable information required for the development of advanced batteries. PMID- 27357606 TI - Loss of membranous VEGFR1 expression is associated with an adverse phenotype and shortened survival in breast cancer. AB - Angiogenesis is a key process in tumor growth and progression, which is controlled by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs). In order to better understand the prevalence and prognostic value of VEGFR1 expression in breast cancer, a tissue microarray containing >2,100 breast cancer specimens, with clinical follow-up data, was analyzed by immunohistochemistry using an antibody directed against the membrane-bound full length receptor protein. The results demonstrated that membranous VEGFR1 staining was detected in all (5 of 5) normal breast specimens. In carcinoma specimens, membranous staining was negative in 3.1%, weak in 6.3%, moderate in 10.9%, and strong in 79.7% of the 1,630 interpretable tissues. Strong staining was significantly associated with estrogen receptor and progesterone receptor expression, but was inversely associated with advanced tumor stage (P=0.0431), high Bloom-Richardson-Ellis Score for Breast Cancer grade and low Ki67 labeling index (both P<0.0001). Cancers with moderate to strong (high) VEGFR1 expression were associated with significantly improved overall survival, as compared with tumors exhibiting negative or weak (low) expression (P=0.0015). This association was also detected in the subset of nodal-positive cancers (P=0.0018), and in the subset of 185 patients who had received tamoxifen as the sole therapy (P=0.001). In conclusion, these data indicated that membrane-bound VEGFR1 is frequently expressed in normal and cancerous breast epithelium. In addition, reduced or lost VEGFR1 expression may serve as a marker for poor prognosis in patients with breast cancer, who might not optimally benefit from endocrine therapy. PMID- 27357607 TI - Development of chrysin loaded poloxamer micelles and toxicity evaluation in fish embryos. AB - Poloxamer micelles promise safety and efficacy for many water insoluble drugs. Chrysin has been reported to have anticancer, anti-inflammatory, antioxidant, and anti-aromatase activities but its water insoluble properties limit its pharmaceutical application. In the present study, chrysin loaded poloxamer micelles were developed. Two types of poloxamers, Pluronic F-68 and Pluronic F 127 were compared. It was found that chrysin loaded Pluronic F-68 micelles (CS P68) and chrysin loaded Pluronic F-127 micelles (CS-P127) obviously increase the aqueous solubility of chrysin. The results also indicated that the type of polymer and ratio of drug to polymer affected size and desirable characteristics of the micelles. The micelle system of CS-P68 and CS-P127 formed at drug to polymer ratios of 1:4 and 1:2, respectively, was found to be the most suitable monodispersed system with a nanosize-range diameter. The in vivo study in zebrafish eggs indicates that the toxicity of CS-P68 and CS-P127 is a dose response. CS-P68 and CS-P127 at a drug dose of 10 ng/mL or less is safe for zebrafish embryo growth. The results of this study indicate enhanced water solubility of chrysin. Chrysin loaded poloxamer micelles are promising for further use in in vivo studies in mammalian animals and humans. PMID- 27357609 TI - Do some deep-sea, sediment-dwelling species of harpacticoid copepods have 1000-km scale range sizes? AB - The range sizes of sediment-dwelling deep-sea species are largely unknown. Such knowledge is important because a deep sea composed in large part of species with 100-km-scale ranges would be very different from one composed predominantly of species with 1000-km-scale ranges. For example, the total species richness would be much greater in the first case than in the second. As a step towards the determination of the distribution of species' range sizes in the deep sea, we asked whether harpacticoid copepods (Crustacea) on the continental rise in the northeastern Pacific had 1000-km-scale range sizes. We chose harpacticoids because they occur widely in deep-sea sediments and thus are a typical deep-sea taxon. In addition, they have no pelagic stage in their life history, so they allow a conservative test of hypotheses about species' range sizes. We used morphology and gene-sequence data to assign individuals to species. At least 13.3% of the species we studied had 1000-km-scale ranges, raising the question of how these species maintain genetic continuity. PMID- 27357608 TI - Reciprocal regulation of long noncoding RNAs THBS4-003 and THBS4 control migration and invasion in prostate cancer cell lines. AB - Increasing evidence implicates long noncoding RNAs (lncRNAs), a class of noncoding RNAs >200 nucleotides in length, in the development of cancer. However, the mechanism underlying the effects of lncRNAs in prostate cancer (PCa) remains to be elucidated. The present study aimed to investigate the role of lncRNA-THBS4 003 in the pathogensis of PCa. In the present study, a microarray containing 8,277 lncRNA probes and 32,207 mRNA probes were used to identify dysregulated mRNAs in three patients with PCa, and reverse transcription-quantitative polymerase chain reaction was used to determine the expression levels of thrombospondin 4 (THBS4) and lncRNA-THBS4-003 in 46 primary PCa and adjacent non tumor tissue samples. The expression levels of THBS4 were determined in six samples of PCa and adjacent non-tumor tissues using Western blot analysis. The effects of forced THBS4 knockdown and lncRNA-THBS4-003 knockdown in the two PCa cell lines, DU145 and PC-3, were evaluated using cell migration and invasion assays, as well as using Western blot analysis. Of the 40,484 probes in the microarray, 354 were significantly upregulated (P<0.05; fold-change >2). The most significantly upregulated mRNA was THBS4. The expression levels of THBS4 and lncRNA-THBS4-003 in the 46 primary PCa samples was significantly higher, compared with that in the adjacent non-tumor tissue samples. Patients with Gleason scores >7 exhibited higher expression levels of lncRNA-THBS4-003, compared with patients with lower scores. Knockdown of THBS4 or lncRNA-THBS4-003 significantly reduced the migratory and invasive abilities of the PCa cells in vitro, and decreased the expression levels of p38 and matrix metalloproteinase (MMP)-9. These findings suggested that the reciprocal regulation of lncRNA-THBS4-003 and THBS4 contributed to the pathogenesis of PCa. Therefore silencing lncRNA-THBS4-003 or THBS4 may inhibit PCa cell migration and invasion, and regulate the levels of MMP 9 through the mitogen-activated protein kinase signaling pathway. PMID- 27357610 TI - Spatially oriented plasmonic 'nanograter' structures. AB - One of the key motivations in producing 3D structures has always been the realization of metamaterials with effective constituent properties that can be tuned in all propagation directions at various frequencies. Here, we report the investigation of spatially oriented "Nanograter" structures with orientation dependent responses over a wide spectrum by focused-ion-beam based patterning and folding of thin film nanostructures. Au nano units of different shapes, standing along specifically designated orientations, were fabricated. Experimental measurements and simulation results show that such structures offer an additional degree of freedom for adjusting optical properties with the angle of inclination, in additional to the size of the structures. The response frequency can be varied in a wide range (8 MUm-14 MUm) by the spatial orientation (0 degrees -180 degrees ) of the structures, transforming the response from magnetic into electric coupling. This may open up prospects for the fabrication of 3D nanostructures as optical interconnects, focusing elements and logic elements, moving toward the realization of 3D optical circuits. PMID- 27357611 TI - The impact of joint partner decision making on obstetric choices and outcomes among Malawian women. AB - OBJECTIVE: To determine the effects of joint partner decision making on obstetric choices and outcomes in Malawi. METHODS: Between July 15, 2014 and February 25, 2015, interviews were performed with women who reported at least one lifetime pregnancy in Lilongwe District, Malawi as part of a cross-sectional study of reproductive decision making. Logistic regression models were applied to examine associations of joint decision making with delivery location and obstetric complications. RESULTS: The study population included 860 women. Women who engaged in joint decision making with partners (adjusted odds ratio [aOR] 4.9; 95% confidence interval [CI] 3.3-7.2) and women whose partners made obstetric care decisions alone (aOR 3.2; 95% CI 2.4-4.4) were more likely to undergo delivery at a healthcare facility compared with women who made obstetric-care decisions individually. In comparison with women who made obstetric decisions individually, no difference in the likelihood of experiencing obstetric complications was observed for women who engaged in joint decision making (aOR 1.1; 95% CI 0.7-1.7) or for women whose partners made decisions individually (aOR 0.8; 95% CI 0.5-1.3). CONCLUSION: In rural Malawi, partner involvement in obstetric decision making was associated with improved obstetric choices. PMID- 27357612 TI - Single-cell pluripotency regulatory networks. AB - Pluripotent stem cells (PSCs) are a popular model system for investigating development, tissue regeneration, and repair. Although much is known about the molecular mechanisms that regulate the balance between self-renewal and lineage commitment in PSCs, the spatiotemporal integration of responsive signaling pathways with core transcriptional regulatory networks are complex and only partially understood. Moreover, measurements made on populations of cells reveal only average properties of the underlying regulatory networks, obscuring their fine detail. Here, we discuss the reconstruction of regulatory networks in individual cells using novel single-cell transcriptomics and proteomics, in order to expand our understanding of the molecular basis of pluripotency, including the role of cell-cell variability within PSC populations, and ways in which networks may be controlled in order to reliably manipulate cell behavior. PMID- 27357613 TI - Letter Regarding Article, "Electrocardiogram in a Patient with Takotsubo Syndrome and Cardiogenic Shock". PMID- 27357614 TI - Off-pump Kommerell's diverticulum resection and descending aorta replacement. AB - We report the case of an unusual variation of a Kommerell's diverticulum in a left aortic arch with an aberrant left subclavian artery, associated with dilatation of the distal aortic arch, surgically treated without the use of extracorporeal circulation. PMID- 27357615 TI - Recent advances in the development of protein tyrosine phosphatase 1B inhibitors for Type 2 diabetes. AB - Diabetes mellitus is the most serious and prevalent metabolic disorders worldwide, complications of which can decrease significantly the quality of life and contribute to premature death. Resistance to insulin is a predominant pathophysiological factor of Type 2 diabetes (T2D). Protein tyrosine phosphatase 1B (PTP1B) is an important negative factor of insulin signal and a potent therapeutic target in T2D patients. This review highlights recent advances (2012 2015) in research related to the role of PTP1B in signal transduction processes implicated in pathophysiology of T2D, and novel PTP1B inhibitors with an emphasis on their chemical structures and modes of action. PMID- 27357617 TI - Next-generation phenotypic screening. AB - Phenotypic drug discovery (PDD) strategies are defined by screening and selection of hit or lead compounds based on quantifiable phenotypic endpoints without prior knowledge of the drug target. We outline the challenges associated with traditional phenotypic screening strategies and propose solutions and new opportunities to be gained by adopting modern PDD technologies. We highlight both historical and recent examples of approved drugs and new drug candidates discovered by modern phenotypic screening. Finally, we offer a prospective view of a new era of PDD underpinned by a wealth of technology advances in the areas of in vitro model development, high-content imaging and image informatics, mechanism-of-action profiling and target deconvolution. PMID- 27357618 TI - How can we address the controversies surrounding the use of NSAIDS in neurodegeneration? PMID- 27357616 TI - Cytokines: roles in atherosclerosis disease progression and potential therapeutic targets. AB - Atherosclerosis, the primary cause of cardiovascular disease (CVD), is a chronic inflammatory disorder in the walls of medium and large arteries. CVD is currently responsible for about one in three global deaths and this is expected to rise in the future due to an increase in the prevalence of obesity and diabetes. Current therapies for atherosclerosis mainly modulate lipid homeostasis and while successful at reducing the risk of a CVD-related death, they are associated with considerable residual risk and various side effects. There is, therefore, a need for alternative therapies aimed at regulating inflammation in order to reduce atherogenesis. This review will highlight the key role cytokines play during disease progression as well as potential therapeutic strategies to target them. PMID- 27357619 TI - Multivalent approaches and beyond: novel tools for the investigation of dopamine D2 receptor pharmacology. AB - The dopamine D2 receptor (D2R) has been implicated in the symptomology of disorders such as schizophrenia and Parkinson's disease. Multivalent ligands provide useful tools to investigate emerging concepts of G protein-coupled receptor drug action such as allostery, bitopic binding and receptor dimerization. This review focuses on the approaches taken toward the development of multivalent ligands for the D2R recently and highlights the challenges associated with each approach, their utility in probing D2R function and approaches to develop new D2R-targeting drugs. Furthermore, we extend our discussion to the possibility of designing multitarget ligands. The insights gained from such studies may provide the basis for improved therapeutic targeting of the D2R. PMID- 27357620 TI - Evolution of the Valley Position in Bulk Transition-Metal Chalcogenides and Their Monolayer Limit. AB - Layered transition metal chalcogenides with large spin orbit coupling have recently sparked much interest due to their potential applications for electronic, optoelectronic, spintronics, and valleytronics. However, most current understanding of the electronic structure near band valleys in momentum space is based on either theoretical investigations or optical measurements, leaving the detailed band structure elusive. For example, the exact position of the conduction band valley of bulk MoS2 remains controversial. Here, using angle resolved photoemission spectroscopy with submicron spatial resolution (micro ARPES), we systematically imaged the conduction/valence band structure evolution across representative chalcogenides MoS2, WS2, and WSe2, as well as the thickness dependent electronic structure from bulk to the monolayer limit. These results establish a solid basis to understand the underlying valley physics of these materials, and also provide a link between chalcogenide electronic band structure and their physical properties for potential valleytronics applications. PMID- 27357622 TI - The use of temporary portocaval shunt as a technical aid in auxiliary orthotopic liver transplantation. PMID- 27357621 TI - Combination therapy in cancer: effects of angiogenesis inhibitors on drug pharmacokinetics and pharmacodynamics. AB - Validated preclinical studies have provided evidence that anti-vascular endothelial growth factor (VEGF) compounds enhance the activity of subsequent antitumor therapy, but the mechanism of this potentiation is far from clear. The most widespread explanation is enhanced delivery of therapeutics due to vascular remodeling, lower interstitial pressure, and increased blood flow. While the antiangiogenic effects on vascular morphology have been fairly consistent in both preclinical and clinical settings, the improvement of tumor vessel function is debated. This review focuses on the effect of anti-VEGF therapy on tumor microenvironment morphology and functions, and its therapeutic benefits when combined with other therapies. The uptake and spatial distribution of chemotherapeutic agents into the tumor after anti-VEGF are examined. PMID- 27357623 TI - Risk stratification of patients with shoulder pain seen in physical therapy practice. AB - RATIONALE, AIMS AND OBJECTIVES: Musculoskeletal shoulder pain is commonly treated in physical therapy. There is inconsistency in the literature regarding patient characteristics related to prognosis. Having prognostic information could be useful for improving clinical efficiency and decreasing the cost of associated care. The objective of this study was to identify predictive characteristics related to patients with shoulder pain who have a high-risk of a bad prognosis (lowest functional recovery compared with visit utilization) as well as those who are at low-risk of a bad prognosis (highest functional recovery compared with visit utilization). METHODS: We completed a secondary analysis of a retrospective cohort using data obtained from an existing commercial outcomes database. Data from 5214 patients with shoulder pain were analysed to determine predictive characteristics that identify patients who either have a low-risk or a high-risk of a bad prognosis to physical therapy care. Multinomial regression was used to identify significant patient characteristics predictive of treatment response. RESULTS: Statistically significant predictors of high-risk categorization included older age, no surgical history, insurance designated as worker's compensation, litigation or automotive and three or more co-morbidities. Predictors of low risk categorization were younger age, shorter duration of symptoms, no surgical history and payer type. CONCLUSION: Selected variables were associated with both poor and good recovery. Further research on prognosis, efficacy of physical therapy care and cost appear warranted for patients with shoulder pain. PMID- 27357624 TI - The awareness of primary caregivers in South Africa of the human rights of their children with intellectual disabilities. AB - BACKGROUND: Besides the right to freedom, human rights can be seen as a basic requirement also for the maintenance of human dignity and the opportunity to thrive - particularly in the case of children with disabilities. It is imperative to explore primary caregivers' awareness of the human rights of their children with intellectual disabilities in view of the role they may play in either facilitating or restricting these rights. This paper explores the awareness of 219 primary caregivers of the human rights of their children with intellectual disabilities. METHOD: A descriptive survey design was used with a custom-designed questionnaire that employed a deductive content analysis based on the articles of the United Nations Convention on the Rights of a Child. Comparisons were drawn between the awareness of primary caregivers from urban and those from rural areas. RESULTS: The majority (85.5%) of participants agreed that their child with intellectual disability had rights. Three broad kinds of right were mentioned (in descending order): provision rights, protection rights and participation rights. Participants from both urban and rural areas mentioned education (a provision right) most frequently. However, participants from urban areas were more aware of the different rights that existed than were their counterparts from rural areas. CONCLUSION: Primary caregivers in both rural and urban areas are aware of the rights of their children with disabilities, although there are significant differences between them. PMID- 27357626 TI - Adenoviral Delivery of Tumor Necrosis Factor-alpha and Interleukin-2 Enables Successful Adoptive Cell Therapy of Immunosuppressive Melanoma. AB - Adoptive T-cell transfer is a promising treatment approach for metastatic cancer, but efficacy in solid tumors has only been achieved with toxic pre- and postconditioning regimens. Thus, adoptive T-cell therapies would benefit from complementary modalities that enable their full potential without excessive toxicity. We aimed to improve the efficacy and safety of adoptive T-cell transfer by using adenoviral vectors for direct delivery of immunomodulatory murine cytokines into B16.OVA melanoma tumors with concomitant T-cell receptor transgenic OT-I T-cell transfer. Armed adenoviruses expressed high local and low systemic levels of cytokine when injected into B16.OVA tumors, suggesting safety of virus-mediated cytokine delivery. Antitumor efficacy was significantly enhanced with adenoviruses coding for murine interleukin-2 (mIL-2) and tumor necrosis factor-alpha (mTNFalpha) when compared with T-cell transfer alone or viruses alone. Further improvement in efficacy was achieved with a triple combination of mIL-2, mTNFalpha, and OT-I T-cells. Mechanistic studies suggest that mIL-2 has an important role in activating T-cells at the tumor, while mTNFalpha induces chemokine expression. Furthermore, adenovirus treatments enhanced tumor-infiltration of OT-I T-cells as demonstrated by SPECT/CT imaging of (111)In-labeled cells. Our results suggest the utility of cytokine-coding adenoviruses for improving the efficacy of adoptive T-cell therapies. PMID- 27357627 TI - Advanced Design of Dumbbell-shaped Genetic Minimal Vectors Improves Non-coding and Coding RNA Expression. AB - Dumbbell-shaped DNA minimal vectors lacking nontherapeutic genes and bacterial sequences are considered a stable, safe alternative to viral, nonviral, and naked plasmid-based gene-transfer systems. We investigated novel molecular features of dumbbell vectors aiming to reduce vector size and to improve the expression of noncoding or coding RNA. We minimized small hairpin RNA (shRNA) or microRNA (miRNA) expressing dumbbell vectors in size down to 130 bp generating the smallest genetic expression vectors reported. This was achieved by using a minimal H1 promoter with integrated transcriptional terminator transcribing the RNA hairpin structure around the dumbbell loop. Such vectors were generated with high conversion yields using a novel protocol. Minimized shRNA-expressing dumbbells showed accelerated kinetics of delivery and transcription leading to enhanced gene silencing in human tissue culture cells. In primary human T cells, minimized miRNA-expressing dumbbells revealed higher stability and triggered stronger target gene suppression as compared with plasmids and miRNA mimics. Dumbbell-driven gene expression was enhanced up to 56- or 160-fold by implementation of an intron and the SV40 enhancer compared with control dumbbells or plasmids. Advanced dumbbell vectors may represent one option to close the gap between durable expression that is achievable with integrating viral vectors and short-term effects triggered by naked RNA. PMID- 27357628 TI - Safety and Efficacy in Advanced Solid Tumors of a Targeted Nanocomplex Carrying the p53 Gene Used in Combination with Docetaxel: A Phase 1b Study. AB - Loss of p53 suppressor function, through mutations or inactivation of the p53 pathway, occurs in most human cancers. SGT-53 is a liposomal nanocomplex designed for systemic, tumor-targeting delivery of the wt p53 gene. In this nanodelivery system, an anti-transferrin receptor single-chain antibody fragment serves as the targeting moiety. In an initial phase 1 trial in patients with advanced solid tumors, SGT-53 demonstrated tumor-specific targeting, was shown to be well tolerated, and was associated with an antitumor effect in several patients. Our preclinical studies have also demonstrated enhanced antitumor activity with the combination of SGT-53 and docetaxel. Thus, this dose-escalation trial was undertaken to assess the combination of SGT-53 and docetaxel for safety and potential efficacy in 14 advanced cancer patients. Results reveal that the combination of SGT-53 (maximum dose, 3.6 mg DNA/infusion) and docetaxel (75 mg/m(2)/infusion) was well tolerated. Moreover, clinical activity involving 12 evaluable patients was observed. Three of these patients achieved RECIST-verified partial responses with tumor reductions of -47%, -51%, and -79%. Two others had stable disease with significant shrinkage (-25% and -16%). These results support phase 2 testing of SGT-53 in combination with docetaxel. PMID- 27357629 TI - Integrated Safety Assessment of 2'-O-Methoxyethyl Chimeric Antisense Oligonucleotides in NonHuman Primates and Healthy Human Volunteers. AB - The common chemical and biological properties of antisense oligonucleotides provide the opportunity to identify and characterize chemical class effects across species. The chemical class that has proven to be the most versatile and best characterized is the 2'-O-methoxyethyl chimeric antisense oligonucleotides. In this report we present an integrated safety assessment of data obtained from controlled dose-ranging studies in nonhuman primates (macaques) and healthy human volunteers for 12 unique 2'-O-methoxyethyl chimeric antisense oligonucleotides. Safety was assessed by the incidence of safety signals in standardized laboratory tests for kidney and liver function, hematology, and complement activation; as well as by the mean test results as a function of dose level over time. At high doses a number of toxicities were observed in nonhuman primates. However, no class safety effects were identified in healthy human volunteers from this integrated data analysis. Effects on complement in nonhuman primates were not observed in humans. Nonhuman primates predicted safe doses in humans, but over predicted risk of complement activation and effects on platelets. Although limited to a single chemical class, comparisons from this analysis are considered valid and accurate based on the carefully controlled setting for the specified study populations and within the total exposures studied. PMID- 27357630 TI - Contribution of human osteoblasts and macrophages to bone matrix degradation and proinflammatory cytokine release after exposure to abrasive endoprosthetic wear particles. AB - One of the major reasons for failure after total joint arthroplasty is aseptic loosening of the implant. At articulating surfaces, defined as the interface between implant and surrounding bone cement, wear particles can be generated and released into the periprosthetic tissue, resulting in inflammation and osteolysis. The aim of the present study was to evaluate the extent to which osteoblasts and macrophages are responsible for the osteolytic and inflammatory reactions following contact with generated wear particles from Ti-6Al-7Nb and Co 28Cr-6Mo hip stems. To this end, human osteoblasts and THP-1 monocytic cells were incubated with the experimentally generated wear particles as well as reference particles (0.01 and 0.1 mg/ml) for 48 h under standard culture conditions. To evaluate the impact of these particles on the two cell types, the release of different bone matrix degrading matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), and relevant cytokines were determined by multiplex enzyme-linked immunosorbent assays. Following incubation with wear particles, human osteoblasts showed a significant upregulation of MMP1 and MMP8, whereas macrophages reacted with enhanced MMP3, MMP8 and MMP10 production. Moreover, the synthesis of TIMPs 1 and 2 was inhibited. The osteoblasts and macrophages also responded with modified expression of the inflammatory mediators interleukin (IL) 6, IL-8, monocyte chemoattractant protein-1 and vascular endothelial growth factor. These results demonstrate that the release of wear particles affects the release of proinflammatory cytokines and has a negative impact on bone matrix formation during the first 48 h of particle exposure. Human osteoblasts are directly involved in the proinflammatory cascade of bone matrix degradation. The simultaneous activation and recruitment of monocytes/macrophages boosted osteolytic processes in the periprosthetic tissue. By the downregulation of TIMP production and the concomitant upregulation of MMPs as a response to particle exposure, bone formation around implants may be suppressed, resulting in implant failure. PMID- 27357631 TI - Genome-editing technologies for gene correction of hemophilia. AB - Hemophilia is caused by various mutations in blood coagulation factor genes, including factor VIII (FVIII) and factor IX (FIX), that encode key proteins in the blood clotting pathway. Although the addition of therapeutic genes or infusion of clotting factors may be used to remedy hemophilia's symptoms, no permanent cure for the disease exists. Moreover, patients often develop neutralizing antibodies or experience adverse effects that limit the therapy's benefits. However, targeted gene therapy involving the precise correction of these mutated genes at the genome level using programmable nucleases is a promising strategy. These nucleases can induce double-strand breaks (DSBs) on genomes, and repairs of such induced DSBs by the two cellular repair systems enable a targeted gene correction. Going beyond cultured cell systems, we are now entering the age of direct gene correction in vivo using various delivery tools. Here, we describe the current status of in vivo and ex vivo genome-editing technology related to potential hemophilia gene correction and the prominent issues surrounding its application in patients with monogenic diseases. PMID- 27357632 TI - Analysis of Lower Breast Pole Length and Nipple-Areola Complex Position Following Superior Pedicle, Short Horizontal Scar Breast Reduction. AB - BACKGROUND: Postoperative changes following superior pedicle breast reduction are closely related to the pattern of skin resection. We have observed that the superior pedicle, short horizontal scar breast reduction technique provides a stable breast shape in the long term. We test the validity of our clinical observations through objective analysis of postoperative dimensional changes following superior pedicle, short horizontal scar breast reduction. METHODS: Of 42 patients who underwent superior pedicle, short horizontal scar breast reductions between January 2011 and June 2012, 38 (75 breasts) were available for long-term follow-up. The midclavicular point-to-superior areolar border distance (A), the inferior areolar border-to-inframammary fold (IMF) distance (B), and the areolar diameter (C) were measured and recorded at the time of (1) preoperative markings, (2) first postoperative visit, and (3) 2-year postoperative follow-up visit. The specifications of the preoperative markings were recorded to analyze their correlation with actual breast dimensions. RESULTS: The superior border of the nipple-areola complex (NAC) was located, on average, 1.2 cm higher at the first postoperative visit when compared with the markings (P < 0.001). The nipple areola position did not change significantly in the long term (P = 0.224). The average postoperative increase in the IMF-to-inferior areolar border distance between the first postoperative visit and the long-term follow-up visit was 0.3 cm (P < 0.001). Although statistically significant, this extent of change (4.5 %) in the lower pole vertical length was clinically unidentifiable, and pseudoptosis did not occur after superior pedicle, short horizontal scar mammaplasty. CONCLUSION: Long-term stability of the NAC position and lower breast pole length makes superior pedicle, short horizontal scar breast reduction a predictable and dependable option for primary breast reduction/mastopexy and for a matching procedure. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 27357633 TI - Topical Vasoconstrictors in Cosmetic Rhinoplasty: Comparative Evaluation of Cocaine Versus Epinephrine Solutions. AB - BACKGROUND: The use of topical vasoconstrictors is a common practice in nasal surgery. These agents reduce bleeding and enable a good surgical field. Topical cocaine and epinephrine, which are frequently used in cosmetic rhinoplasty, are considered safe and effective, but secondary effects have been described. The aim of the present study was to evaluate and compare the benefits and risks of epinephrine and cocaine employed as topical vasoconstrictive agents in cosmetic rhinoplasty. METHODS: This prospective non-randomised study included 65 consecutive female patients undergoing primary closed rhinoplasty. Patients were treated with topical aqueous solutions of 4 % cocaine (n = 33) or 1:1000 epinephrine (n = 32). Benefits and risks of drug use were compared between groups. Vasoconstriction was assessed by quantitative and qualitative evaluation of bleeding during surgery. Systemic effects were studied in terms of cardiovascular changes during the procedure. The Mann-Whitney test and mixed effects models were used to compare continuous variables and to assess the effects of vasoconstrictor treatment, respectively. RESULTS: Cocaine exerted a stronger and more predictable vasoconstrictive effect than epinephrine. This difference was linked to better field quality, but did not relate to shorter surgery times. Increased heart rate was detected with both agents and was significantly higher with cocaine (p < 0.05). Blood pressure did not significantly differ between groups. CONCLUSIONS: Both cocaine and epinephrine, at the concentrations used in this study, are suitable as topical vasoconstrictive agents in aesthetic rhinoplasty. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 27357634 TI - Patient-Reported Outcome Instruments for Surgical and Traumatic Scars: A Systematic Review of their Development, Content, and Psychometric Validation. AB - BACKGROUND: Patient-reported outcomes (PROs) are of growing importance in research and clinical care and may be used as primary outcomes or as compliments to traditional surgical outcomes. In assessing the impact of surgical and traumatic scars, PROs are often the most meaningful. To assess outcomes from the patient perspective, rigorously developed and validated PRO instruments are essential. METHODS: The authors conducted a systematic literature review to identify PRO instruments developed and/or validated for patients with surgical and/or non-burn traumatic scars. Identified instruments were assessed for content, development process, and validation under recommended guidelines for PRO instrument development. RESULTS: The systematic review identified 6534 articles. After review, we identified four PRO instruments meeting inclusion criteria: patient and observer scar assessment scale (POSAS), bock quality of life questionnaire for patients with keloid and hypertrophic scarring (Bock), patient scar assessment questionnaire (PSAQ), and patient-reported impact of scars measure (PRISM). Common concepts measured were symptoms and psychosocial well being. Only PSAQ had a dedicated appearance domain. Qualitative data were used to inform content for the PSAQ and PRISM, and a modern psychometric approach (Rasch Measurement Theory) was used to develop PRISM and to test POSAS. Overall, PRISM demonstrated the most rigorous design and validation process, however, was limited by the lack of a dedicated appearance domain. CONCLUSIONS: PRO instruments to evaluate outcomes in scars exist but vary in terms of concepts measured and psychometric soundness. This review discusses the strengths and weaknesses of existing instruments, highlighting the need for future scar-focused PRO instrument development. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 27357635 TI - Thumb Tip Defect Reconstruction Using Neurovascular Island Pedicle Flap Obtained From Long Finger. AB - INTRODUCTION: Thumb tip reconstruction has been a very challenging issue for hand surgeons. Varieties of reconstructive options have been described or modified to obtain satisfactory sensory recovery. However, none has yielded entirely satisfactory results. This study reports a retrospective review of clinical data records of patients treated with a neurovascular island pedicle flap obtained from the medial aspect of the long finger. METHODS: We enrolled 15 patients (9 men and 6 women), who received neurovascular island pedicle flaps for thumb tip amputations between December 2011 and December 2015. The average size of the flap was 2.8 * 2.2 cm(2) (range 2.5 * 1.8 cm(2) to 3.5 * 2.5 cm(2)). At the final follow-up visits, static two-point discrimination, visual analogue scale, Michigan hand outcome questionnaire and return-to-work time were used to evaluate surgical outcomes. RESULTS: All flaps survived well. The follow-up period was 18 months. The mean static 2PD values at the reconstructed thumb tip and donor finger pulp (medial side) were 5.3 mm (range 4-8 mm) and 3.2 mm (range 3-4 mm), respectively. The average VAS scores for the aesthetic appearance of the donor site and recipient site were 9.1 (range 8-10) and 9.0 (range 8-9.5), respectively. The average Michigan Hand Outcome Questionnaire (MHOQ) score for hand function (reconstructed hand) was 8.2 (range 6-16). The average RTW time was 8.4 weeks (range 7-12 weeks). CONCLUSIONS: Neurovascular island pedicle flap obtained from the medial aspect of long finger is a very reliable alternative technique for thumb tip defect reconstruction. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 27357639 TI - Health Self-Efficacy Among Populations with Multiple Chronic Conditions: the Value of Patient-Centered Communication. AB - INTRODUCTION: Using cross-sectional survey data, we assessed the association between chronic illness burden and health-related self-efficacy, evaluating whether patient-centered communication is associated with self-efficacy and if that relationship varies by chronic illness burden. METHODS: Data were from the Health Information National Trends Survey, a cross-sectional survey of the US adult population collected in 2012-2013 (n = 3630). Health-related self-efficacy was measured with the item: "Overall, how confident are you about your ability to take good care of your health?" and the prevalence of six chronic conditions and depression/anxiety was assessed. Patient-centered communication was measured as the frequency with which respondents perceived their healthcare providers allowed them to ask questions, gave attention to their emotions, involved them in decisions, made sure they understood how to take care of their health, helped them to deal with uncertainty, and if they felt they could rely on their healthcare providers to take care of their healthcare needs. RESULTS: Health related self-efficacy was significantly lower among individuals with greater illness burden. In adjusted analysis, individuals who experienced more positive patient-centered communication reported higher levels of self-efficacy (beta = 0.26, P < 0.0001); this association was strongest among those with greater illness burden. CONCLUSION: Higher levels of self-efficacy were observed among patients reporting more positive patient-centered communication; the observed association was stronger among those with greater chronic illness burden. PMID- 27357638 TI - Calmodulin/CaMKII inhibition improves intercellular communication and impulse propagation in the heart and is antiarrhythmic under conditions when fibrosis is absent. AB - AIM: In healthy hearts, ventricular gap junctions are mainly composed by connexin43 (Cx43) and localize in the intercalated disc, enabling appropriate electrical coupling. In diseased hearts, Cx43 is heterogeneously down-regulated, whereas activity of calmodulin/calcium-calmodulin protein kinase II (CaM/CaMKII) signalling increases. It is unclear if CaM/CaMKII affects Cx43 expression/localization or impulse propagation. We analysed different models to assess this. METHODS AND RESULTS: AC3-I mice with CaMKII genetically inhibited were subjected to pressure overload (16 weeks, TAC vs. sham). Optical and epicardial mapping was performed on Langendorff-perfused rabbit and AC3-I hearts, respectively. Cx43 subcellular distribution from rabbit/mouse ventricles was evaluated by immunoblot after Triton X-100-based fractionation. In mice with constitutively reduced CaMKII activity (AC3-I), conduction velocity (CV) was augmented (n = 11, P < 0.01 vs. WT); in AC3-I, CV was preserved after TAC, in contrast to a reduction seen in TAC-WT mice (-20%). Cx43 expression was preserved after TAC in AC3-I mice, though arrhythmias and fibrosis were still present. In rabbits, W7 (CaM inhibitor, 10 uM) increased CV (6-13%, n= 6, P< 0.05), while susceptibility to arrhythmias decreased. Immunoconfocal microscopy revealed enlarged Cx43 cluster sizes at intercalated discs of those hearts. Total Cx43 did not change by W7 (n= 4), whereas Triton X-100 insoluble Cx43 increased (+21%, n= 4, P< 0.01). Similar findings were obtained in AC3-I mouse hearts when compared with control, and in cultured dog cardiomyocytes. Functional implication was shown through increased intercellular coupling in cultured neonatal rat cardiomyocytes. CONCLUSION: Both acute and chronic CaM/CaMKII inhibition improves conduction characteristics and enhances localization of Cx43 in the intercalated disc. In the absence of fibrosis, this reduced the susceptibility for arrhythmias. PMID- 27357636 TI - Identifying circulating microRNAs as biomarkers of cardiovascular disease: a systematic review. AB - The aim of the present study is to identify microRNAs (miRs) with high potential to be used as biomarkers in plasma and/or serum to clinically diagnose, or provide accurate prognosis for survival in, patients with atherosclerosis, coronary artery disease, and acute coronary syndrome (ACS). A systematic search of published original research yielded a total of 72 studies. After review of the risk of bias of the published studies, according to Cochrane Collaboration and the QUADUAS Group standards, 19 studies were selected. Overall 52 different miRs were reported. In particular, miR-133a/b (5 studies), miR-208a/b (6 studies), and miR-499 (7 studies) were well studied and found to be significant diagnostic and/or prognostic markers across different cardiovascular disease progression stages. miR-1 and miR-145b are potential biomarkers of ACS; miR-1 with higher sensitivity for all acute myocardial infarction (AMI), and miR-145 for STEMI and worse outcome of AMI. But when miRs were studied across different ACS study populations, patients had varying degrees of coronary stenosis, which was identified as an important confounder that limited the ability to quantitatively pool the study results. The identified miRs were found to regulate endothelial function and angiogenesis (miR-1, miR-133), vascular smooth muscle cell differentiation (miR-133, miR-145), communication between vascular smooth muscle and endothelial cell to stabilize plaques (miR-145), apoptosis (miR-1, miR-133, miR-499), cardiac myocyte differentiation (miR-1, miR-133, miR-145, miR-208, miR 499), and to repress cardiac hypertrophy (miR-133). Their role in these processes may be explained by regulation of shared RNA targets such as cyclin-dependent kinase inhibitor 1A (or p21), ETS proto-oncogene 1, fascin actin-bundling protein 1, hyperpolarization-activated cyclic nucleotide-gated potassium channel 4, insulin-like growth factor 1 receptor LIM and SH3 protein 1, purine nucleoside phosphorylase, and transgelin 2. These mechanistic data further support the clinical relevance of the identified miRs. miR-1, miR-133a/b, miR-145, miR 208a/b, and miR-499(a) in plasma and/or serum show some potential for diagnosis of cardiovascular disease. However, biased selection of miRs in most studies and unexplained contrasting results are major limitations of current miR research. Inconsistencies need to be addressed in order to definitively identify clinically useful miRs. Therefore, this paper presents important aspects to improve future miR research, including unbiased selection of miRs, standardization/normalization of reference miRs, adjustment for patient comorbidities and medication, and robust protocols of data-sharing plans that could prevent selective publication and selective reporting of miR research outcomes. PMID- 27357637 TI - Heterogeneity in the lymphatic vascular system and its origin. AB - Lymphatic vessels have historically been viewed as passive conduits for fluid and immune cells, but this perspective is increasingly being revised as new functions of lymphatic vessels are revealed. Emerging evidence shows that lymphatic endothelium takes an active part in immune regulation both by antigen presentation and expression of immunomodulatory genes. In addition, lymphatic vessels play an important role in uptake of dietary fat and clearance of cholesterol from peripheral tissues, and they have been implicated in obesity and arteriosclerosis. Lymphatic vessels within different organs and in different physiological and pathological processes show a remarkable plasticity and heterogeneity, reflecting their functional specialization. In addition, lymphatic endothelial cells (LECs) of different organs were recently shown to have alternative developmental origins, which may contribute to the development of the diverse lymphatic vessel and endothelial functions seen in the adult. Here, we discuss recent developments in the understanding of heterogeneity within the lymphatic system considering the organ-specific functional and molecular specialization of LECs and their developmental origin. PMID- 27357641 TI - The Sydney West Knowledge Portal: Evaluating the Growth of a Knowledge Portal to Support Translational Research. AB - BACKGROUND: The Sydney West Translational Cancer Research Centre is an organization funded to build capacity for translational research in cancer. Translational research is essential for ensuring the integration of best available evidence into practice and for improving patient outcomes. However, there is a low level of awareness regarding what it is and how to conduct it optimally. One solution to addressing this gap is the design and deployment of web-based knowledge portals to disseminate new knowledge and engage with and connect dispersed networks of researchers. A knowledge portal is an web-based platform for increasing knowledge dissemination and management in a specialized area. OBJECTIVE: To measure the design and growth of an web-based knowledge portal for increasing individual awareness of translational research and to build organizational capacity for the delivery of translational research projects in cancer. METHODS: An adaptive methodology was used to capture the design and growth of an web-based knowledge portal in cancer. This involved stakeholder consultations to inform initial design of the portal. Once the portal was live, site analytics were reviewed to evaluate member usage of the portal and to measure growth in membership. RESULTS: Knowledge portal membership grew consistently for the first 18 months after deployment, before leveling out. Analysis of site metrics revealed members were most likely to visit portal pages with community-generated content, particularly pages with a focus on translational research. This was closely followed by pages that disseminated educational material about translational research. CONCLUSIONS: Preliminary data from this study suggest that knowledge portals may be beneficial tools for translating new evidence and fostering an environment of communication and collaboration. PMID- 27357640 TI - Human GV oocytes generated by mitotically active germ cells obtained from follicular aspirates. AB - Human female germline stem cells (FGSCs) have opened new opportunities for understanding human oogenesis, delaying menopause, treating infertility, and providing a new strategy for preserving fertility. However, the shortage of adult human ovaries tissues available impedes their future investigations and clinical applications. Here, we have established FGSC lines from scarce ovarian cortical tissues that exist in follicular aspirates (faFGSCs), which are produced and discarded in in vitro fertilization centers worldwide. The faFGSCs have characteristics of germline stem cells involved in the gene expression profile, growth characteristics, and a normal karyotype consistent with that of FGSCs obtained from ovarian cortexes surgically removed from patients (srFGSCs). Furthermore, faFGSCs have developmental potentials including spontaneous differentiation into oocytes under feeder-free conditions, communicating with granulosa cells by gap junctions and paracrine factors, entering meiosis after RA induction, as well as forming follicles after injection into human ovarian cortical tissues xenografted into adult immunodeficient female mice. Lastly, we developed a strategy guiding FGSCs differentiated into germinal vesicle (GV) stage oocytes in vitro and revealed their developmental mechanisms. Our study not only provides a new approach to obtain human FGSCs for medical treatment, but also opens several avenues to investigate human oogenesis in vitro. PMID- 27357642 TI - Commentary. PMID- 27357643 TI - Density functional theory with modified dispersion correction for metals applied to molecular adsorption on Pt(111). AB - We have performed density functional theory calculations using our modified DFT D2 dispersion correction for metals to investigate adsorption of a range of molecules on Pt(111). The agreement between our calculations and experimental adsorption energies ranging from 0 to 3 eV was excellent with a mean absolute deviation of 0.19 eV and a maximum deviation of 0.37 eV. Our results show that the DFT-D2 semiempirical dispersion correction can provide accurate results also for describing adsorption on metals, provided that relevant physical properties of the system are taken into account, such as shorter ranged dispersion because of screening by the conducting electrons and a lower polarizability of the core electrons in metals compared to isolated atoms. PMID- 27357644 TI - Protective effect of magnolol-loaded polyketal microparticles on lipopolysaccharide-induced acute lung injury in rats. AB - Magnolol has shown inhibitory effects on NO production and TNF-alpha production in lipopolysaccharide (LPS)-activated macrophages and LPS-induced acute lung injury; however, the poor solubility of magnolol has hindered its clinical success. In this study, magnolol-loaded microparticles were prepared via single emulsion method from a polyketal polymer, termed PK3. The particle sizes of magnolol-loaded PK3 microparticle is 3.73 +/- 0.41 MUm, and was suitable for phagocytosis by macrophages and pulmonary drug delivery. PK3 microparticles exhibited excellent biocompatibility both in vitro and in vivo. More importantly, intratracheal delivery of these magnolol-loaded microparticles significantly reduced the lung inflammatory responses at low dosage of magnolol (0.5 mg/kg), and have great clinical potential in treating acute lung injury. PMID- 27357645 TI - FDG-PET for Prediction of AD Dementia in Mild Cognitive Impairment. A Review of the State of the Art with Particular Emphasis on the Comparison with Other Neuroimaging Modalities (MRI and Perfusion SPECT). AB - This review article aims at providing a state-of-the-art review of the role of fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging (FDG-PET) in the prediction of Alzheimer's dementia in subjects suffering mild cognitive impairment (MCI), with a particular focus on the predictive power of FDG-PET compared to structural magnetic resonance imaging (sMRI). We also address perfusion single photon emission computed tomography (SPECT) as a less costly and more accessible alternative to FDG-PET. A search in PubMed was performed, taking into consideration relevant scientific articles published in English within the last five years and limited to human studies. This recent literature confirms the effectiveness of FDG-PET and sMRI for prediction of AD dementia in MCI. However, there are discordant results regarding which image modality is superior. This could be explained by the high variability of metrics used to evaluate both imaging modalities and/or by sampling/population issues such as age, disease severity and conversion time. FDG-PET seems to outperform sMRI in rapidly converting early-onset MCI individuals, whereas sMRI may outperform FDG-PET in late-onset MCI subjects, in which case FDG PET might only provide a complementary role. Although FDG-PET performs better than perfusion SPECT, current evidence confirms perfusion SPECT as a valid alternative when FDG- PET is not available. Finally, possible future directions in the field are discussed. PMID- 27357646 TI - Prevalence of the Use of Opioids for Treatment of Pain in Persons with a Cognitive Impairment Compared with Cognitively Intact Persons: A Systematic Review. AB - AIM: To describe the prevalence of opioid use in persons with a cognitive impairment compared with cognitively intact persons and to explore factors associated with opioid prescription. METHOD: A search was made in PubMed (Medline), Embase, Cochrane, Central, Cinahl, PsychInfo and Web of Science and additional articles were identified by manual search of reference lists. Titles and abstracts were screened and eligible articles reviewed in full-text. A citation check was performed on the included articles for a complete search. Risk of bias of the included studies was assessed using an appropriate tool. RESULTS: The search yielded 610 unique hits and an additional 33 records were identified via reference checking. After screening, 23 studies were included. A citation tracking was performed for these 23 articles using Web of Science, which yielded an additional 421 articles for a second screening. After the second screening, 24 studies were included. Opioid use was divided into three classes: weak, strong, and weak and strong combined. In several articles there were more than one study conclusion on different opioid classes or in a different setting. Analysis was performed on the prevalence of opioid use (prescription rates) and the dosage of opioids. The 24 studies yielded a total of 35 study conclusions related to prescription rates and dosage. Of these, four showed a higher use of opioids in persons with a cognitive impairment, 14 an equal distribution, and 17 showed lower opioid use in cognitively impaired persons. CONCLUSION: This systematic review provides evidence for general undertreatment of pain with opioids in persons with a cognitive impairment. PMID- 27357647 TI - Nanocapsulated Ascorbic Acid in Combating Cerebral Ischemia Reperfusion- Induced Oxidative Injury in Rat Brain. AB - Recent evidences suggest that cerebral ischemia-reperfusion insult plays significant role in pathogenic diseases like Alzheimer's disease (AD) and other neurodegenerative diseases. Toxic reactive oxygen species (ROS) generated by induced oxidative stress in the episodes of cerebral ischemia-reperfusion (CIR) plays major role in neurodegeneration. As the prime source of ROS generation, neuronal mitochondria, the cellular energy metabolic centre experience severe damage because of CIR-induced oxidative stress. The process of mitochondrial dysfunction is accelerated by CIR that may pave the pathway for neurodegeneration in AD among aged individuals. Prevention of CIR injury may be a shunt in order to minimize the risk of dementia of Alzheimer's type in aged individuals. The use of chemical antioxidants in CIR is not suitable as the blood- brain barrier (BBB) doesn't allow the entry of molecules from blood circulation into the brain. Thus L-ascorbic acid loaded polylactide nanocapsules were prepared and fed orally to assess the role of nanocapsulated ascorbic acid (NAA) against CIR induced oxidative injury in mitochondrial region of rat brains. Mitochondrial injury was assessed by the extent of lipid peroxidation and in situ antioxidant enzyme status. The levels of cytochrome c (cyt c), cyclooxygenase- 2 (COX-2) and iNOS were determined. Results showed that in comparison to free ascorbic acid (AA), NAA exerted better protection to the brain mitochondria by preventing oxidative damage in ROS mediated CIR injury. PMID- 27357648 TI - Targeting Ras Activity Prevented Amyloid Beta-Induced Aberrant Neuronal Cell Cycle Re-Entry and Death. AB - Several studies suggest that soluble Amyloid beta (Abeta) oligomer-induced aberrant neuronal cell cycle re-entry is the initial trigger for a significant part of the neuronal degeneration and loss in Alzheimer's disease (AD). In this study, we investigated the role of Ras, which is a well-known protooncoprotein, in soluble Abeta oligomer-induced aberrant neuronal cell cycle activation and subsequent cell loss using retinoic acid differentiated human SH-SY5Y neuroblastoma cells as model system. In line with previous literature, we showed that in vitro preparations of soluble Abeta42 oligomers triggered cell cycle activation but not cell proliferation. As a new finding, we showed that Farnesylthiosalicylic acid (FTS), a specific chemical Ras inhibitor, prevented soluble Abeta42 oligomer preparation-induced cell cycle activation. Moreover, we showed that the expression of dominant negative mutant H-Ras (S17N) prevented soluble Abeta42 oligomer preparation-induced cell cycle activation, confirming the specific role of Ras in this pathway. As a possible better mimic of the situation in the AD brain, we prepared soluble oligomers from Abeta42 : Abeta40 (3:7) peptide mixture and showed that this oligomer preparation similarly induced cell cycle activation which was also inhibited by the Ras inhibitor. Finally, we showed that FTS prevented soluble Abeta42 oligomer preparationinduced cell death in our retinoic acid differentiated SH-SY5Y cells. Overall, our results strongly suggest that Ras activity is required for soluble Abeta oligomer-induced aberrant neuronal cell cycle reentry and subsequent neuronal loss, which are considered important mechanisms in AD pathogenesis. PMID- 27357649 TI - MCOLN1 is a ROS sensor in lysosomes that regulates autophagy. AB - Cellular stresses trigger autophagy to remove damaged macromolecules and organelles. Lysosomes 'host' multiple stress-sensing mechanisms that trigger the coordinated biogenesis of autophagosomes and lysosomes. For example, transcription factor (TF)EB, which regulates autophagy and lysosome biogenesis, is activated following the inhibition of mTOR, a lysosome-localized nutrient sensor. Here we show that reactive oxygen species (ROS) activate TFEB via a lysosomal Ca(2+)-dependent mechanism independent of mTOR. Exogenous oxidants or increasing mitochondrial ROS levels directly and specifically activate lysosomal TRPML1 channels, inducing lysosomal Ca(2+) release. This activation triggers calcineurin-dependent TFEB-nuclear translocation, autophagy induction and lysosome biogenesis. When TRPML1 is genetically inactivated or pharmacologically inhibited, clearance of damaged mitochondria and removal of excess ROS are blocked. Furthermore, TRPML1's ROS sensitivity is specifically required for lysosome adaptation to mitochondrial damage. Hence, TRPML1 is a ROS sensor localized on the lysosomal membrane that orchestrates an autophagy-dependent negative-feedback programme to mitigate oxidative stress in the cell. PMID- 27357654 TI - Ethnic Comparisons in HIV Testing Attitudes, HIV Testing, and Predictors of HIV Testing Among Black and White College Students. AB - OBJECTIVES: This study's primary aim was to examine ethnic differences in predictors of HIV testing among Black and White college students. We also examined ethnic differences in sexual risk behaviors and attitudes toward the importance of HIV testing. PARTICIPANTS/METHOD: An analytic sample of 126 Black and 617 White undergraduatestudents aged 18-24 were analyzed for a subset of responses on the American College Health Association-National College Health Assessment II (ACHA-NCHA II) (2012) pertaining to HIV testing, attitudes about the importance of HIV testing, and sexual risk behaviors. Predictors of HIV testing behavior were analyzed using logistic regression. t tests and chi-square tests were performed to access differences in HIV test history, testing attitudes, and sexual risk behaviors. RESULTS: Black students had more positive attitudes toward testing and were more likely to have been tested for HIV compared to White students. A greater number of sexual partners and more positive HIV testing attitudes were significant predictors of HIV testing among White students, whereas relationship status predicted testing among Black students. Older age and history of ever having sex were significant predictors of HIV testing for both groups. There were no significant differences between groups in number of sexual partners or self-reports in history of sexual experience (oral, vaginal, or anal). CONCLUSIONS: Factors that influence HIV testing may differ across racial/ethnic groups. Findings support the need to consider racial/ethnic differences in predictors of HIV testing during the development and tailoring of HIV testing prevention initiatives targeting college students. PMID- 27357655 TI - In vitro synergistic combinations of pentamidine, polymyxin B, tigecycline and tobramycin with antifungal agents against Fusarium spp. AB - The genus Fusarium is characterized by hyaline filamentous fungi that cause infections predominantly in immunocompromised patients. The remarkable primary resistance to antifungal agents of this genus requires a search for new therapeutic possibilities. This study assessed the in vitro susceptibility of 25 clinical isolates of Fusarium against antifungal agents (amphotericin B, caspofungin, itraconazole and voriconazole) and antimicrobials (pentamidine, polymyxin B, tigecycline and tobramycin) according to the broth microdilution method (M38-A2). The interactions between antifungal and antimicrobial agents were evaluated by the microdilution checkerboard method. Pentamidine and polymyxin B showed MIC values >=4 ug ml-1 against Fusarium spp. The highest rates of synergism were observed when amphotericin B or voriconazole was combined with tobramycin (80 % and 76 %, respectively), polymyxin B (76 % and 64 %) and pentamidine (72 % and 68 %). The most significant combinations deserve in vivo evaluations in order to verify their potential in the treatment of fusariosis. PMID- 27357656 TI - Mefloquine induces ROS mediated programmed cell death in malaria parasite: Plasmodium. AB - Recent studies pioneer the existence of a novel programmed cell death pathway in malaria parasite plasmodium and suggest that it could be helpful in developing new targeted anti-malarial therapies. Considering this fact, we evaluated the underlying action mechanism of this pathway in mefloquine (MQ) treated parasite. Since cysteine proteases play a key role in apoptosis hence we performed preliminary computational simulations to determine binding affinity of MQ with metacaspase protein model. Binding pocket identified using computational studies, was docked with MQ to identify it's potential to bind with the predicted protein model. We further determined apoptotic markers such as mitochondrial dysregulation, activation of cysteine proteases and in situ DNA fragmentation in MQ treated/untreated parasites by cell based assay. Our results showed low mitochondrial membrane potential, enhanced activity of cysteine protease and increased number of fragmented DNA in treated parasites compared to untreated ones. We next tested the involvement of oxidative stress in MQ mediated cell death and found significant increase in reactive oxygen species generation after 24 h of treatment. Therefore we conclude that apart from hemozoin inhibition, MQ is competent to induce apoptosis in plasmodium by activating metacaspase and ROS production. PMID- 27357657 TI - FADD is a key regulator of lipid metabolism. AB - FADD, a classical apoptotic signaling adaptor, was recently reported to have non apoptotic functions. Here, we report the discovery that FADD regulates lipid metabolism. PPAR-alpha is a dietary lipid sensor, whose activation results in hypolipidemic effects. We show that FADD interacts with RIP140, which is a corepressor for PPAR-alpha, and FADD phosphorylation-mimic mutation (FADD-D) or FADD deficiency abolishes RIP140-mediated transcriptional repression, leading to the activation of PPAR-alpha. FADD-D-mutant mice exhibit significantly decreased adipose tissue mass and triglyceride accumulation. Also, they exhibit increased energy expenditure with enhanced fatty acid oxidation in adipocytes due to the activation of PPAR-alpha. Similar metabolic phenotypes, such as reduced fat formation, insulin resistance, and resistance to HFD-induced obesity, are shown in adipose-specific FADD knockout mice. Additionally, FADD-D mutation can reverse the severe genetic obesity phenotype of ob/ob mice, with elevated fatty acid oxidation and oxygen consumption in adipose tissue, improved insulin resistance, and decreased triglyceride storage. We conclude that FADD is a master regulator of glucose and fat metabolism with potential applications for treatment of insulin resistance and obesity. PMID- 27357658 TI - Structural basis for sulfation-dependent self-glycan recognition by the human immune-inhibitory receptor Siglec-8. AB - Siglec-8 is a human immune-inhibitory receptor that, when engaged by specific self-glycans, triggers eosinophil apoptosis and inhibits mast cell degranulation, providing an endogenous mechanism to down-regulate immune responses of these central inflammatory effector cells. Here we used solution NMR spectroscopy to dissect the fine specificity of Siglec-8 toward different sialylated and sulfated carbohydrate ligands and determined the structure of the Siglec-8 lectin domain in complex with its prime glycan target 6'-sulfo sialyl Lewis(x) A canonical motif for sialic acid recognition, extended by a secondary motif formed by unique loop regions, recognizing 6-O-sulfated galactose dictates tight specificity distinct from other Siglec family members and any other endogenous glycan recognition receptors. Structure-guided mutagenesis revealed key contacts of both interfaces to be equally essential for binding. Our work provides critical structural and mechanistic insights into how Siglec-8 selectively recognizes its glycan target, rationalizes the functional impact of site-specific glycan sulfation in modulating this lectin-glycan interaction, and will enable the rational design of Siglec-8-targeted agonists to treat eosinophil- and mast cell related allergic and inflammatory diseases, such as asthma. PMID- 27357659 TI - piRNA pathway is not required for antiviral defense in Drosophila melanogaster. AB - Since its discovery, RNA interference has been identified as involved in many different cellular processes, and as a natural antiviral response in plants, nematodes, and insects. In insects, the small interfering RNA (siRNA) pathway is the major antiviral response. In recent years, the Piwi-interacting RNA (piRNA) pathway also has been implicated in antiviral defense in mosquitoes infected with arboviruses. Using Drosophila melanogaster and an array of viruses that infect the fruit fly acutely or persistently or are vertically transmitted through the germ line, we investigated in detail the extent to which the piRNA pathway contributes to antiviral defense in adult flies. Following virus infection, the survival and viral titers of Piwi, Aubergine, Argonaute-3, and Zucchini mutant flies were similar to those of wild type flies. Using next-generation sequencing of small RNAs from wild type and siRNA mutant flies, we showed that no viral derived piRNAs were produced in fruit flies during different types of viral infection. Our study provides the first evidence, to our knowledge, that the piRNA pathway does not play a major role in antiviral defense in adult Drosophila and demonstrates that viral-derived piRNA production depends on the biology of the host-virus combination rather than being part of a general antiviral process in insects. PMID- 27357660 TI - Borrowed alleles and convergence in serpentine adaptation. AB - Serpentine barrens represent extreme hazards for plant colonists. These sites are characterized by high porosity leading to drought, lack of essential mineral nutrients, and phytotoxic levels of metals. Nevertheless, nature forged populations adapted to these challenges. Here, we use a population-based evolutionary genomic approach coupled with elemental profiling to assess how autotetraploid Arabidopsis arenosa adapted to a multichallenge serpentine habitat in the Austrian Alps. We first demonstrate that serpentine-adapted plants exhibit dramatically altered elemental accumulation levels in common conditions, and then resequence 24 autotetraploid individuals from three populations to perform a genome scan. We find evidence for highly localized selective sweeps that point to a polygenic, multitrait basis for serpentine adaptation. Comparing our results to a previous study of independent serpentine colonizations in the closely related diploid Arabidopsis lyrata in the United Kingdom and United States, we find the highest levels of differentiation in 11 of the same loci, providing candidate alleles for mediating convergent evolution. This overlap between independent colonizations in different species suggests that a limited number of evolutionary strategies are suited to overcome the multiple challenges of serpentine adaptation. Interestingly, we detect footprints of selection in A. arenosa in the context of substantial gene flow from nearby off-serpentine populations of A. arenosa, as well as from A. lyrata In several cases, quantitative tests of introgression indicate that some alleles exhibiting strong selective sweep signatures appear to have been introgressed from A. lyrata This finding suggests that migrant alleles may have facilitated adaptation of A. arenosa to this multihazard environment. PMID- 27357662 TI - Holsteins are the genomic selection poster cows. PMID- 27357663 TI - Avoid the hard problem: Employment of mental simulation for prediction is already a crucial step. PMID- 27357661 TI - Structural model of the dimeric Parkinson's protein LRRK2 reveals a compact architecture involving distant interdomain contacts. AB - Leucine-rich repeat kinase 2 (LRRK2) is a large, multidomain protein containing two catalytic domains: a Ras of complex proteins (Roc) G-domain and a kinase domain. Mutations associated with familial and sporadic Parkinson's disease (PD) have been identified in both catalytic domains, as well as in several of its multiple putative regulatory domains. Several of these mutations have been linked to increased kinase activity. Despite the role of LRRK2 in the pathogenesis of PD, little is known about its overall architecture and how PD-linked mutations alter its function and enzymatic activities. Here, we have modeled the 3D structure of dimeric, full-length LRRK2 by combining domain-based homology models with multiple experimental constraints provided by chemical cross-linking combined with mass spectrometry, negative-stain EM, and small-angle X-ray scattering. Our model reveals dimeric LRRK2 has a compact overall architecture with a tight, multidomain organization. Close contacts between the N-terminal ankyrin and C-terminal WD40 domains, and their proximity-together with the LRR domain-to the kinase domain suggest an intramolecular mechanism for LRRK2 kinase activity regulation. Overall, our studies provide, to our knowledge, the first structural framework for understanding the role of the different domains of full length LRRK2 in the pathogenesis of PD. PMID- 27357664 TI - Insects cannot tell us anything about subjective experience or the origin of consciousness. PMID- 27357665 TI - Consciousness explained or consciousness redefined? PMID- 27357666 TI - QnAs with Jorge Galan. PMID- 27357667 TI - Early multisensory integration of self and source motion in the auditory system. AB - Discriminating external from self-produced sensory inputs is a major challenge for brains. In the auditory system, sound localization must account for movements of the head and ears, a computation likely to involve multimodal integration. Principal neurons (PNs) of the dorsal cochlear nucleus (DCN) are known to be spatially selective and to receive multimodal sensory information. We studied the responses of PNs to body rotation with or without sound stimulation, as well as to sound source rotation with stationary body. We demonstrated that PNs are sensitive to head direction, and, in the presence of sound, they differentiate between body and sound source movement. Thus, the output of the DCN provides the brain with enough information to disambiguate the movement of a sound source from an acoustically identical relative movement produced by motion of the animal. PMID- 27357668 TI - Mapping out spin and particle conductances in a quantum point contact. AB - We study particle and spin transport in a single-mode quantum point contact, using a charge neutral, quantum degenerate Fermi gas with tunable, attractive interactions. This yields the spin and particle conductance of the point contact as a function of chemical potential or confinement. The measurements cover a regime from weak attraction, where quantized conductance is observed, to the resonantly interacting superfluid. Spin conductance exhibits a broad maximum when varying the chemical potential at moderate interactions, which signals the emergence of Cooper pairing. In contrast, the particle conductance is unexpectedly enhanced even before the gas is expected to turn into a superfluid, continuously rising from the plateau at [Formula: see text] for weak interactions to plateau-like features at nonuniversal values as high as [Formula: see text] for intermediate interactions. For strong interactions, the particle conductance plateaus disappear and the spin conductance gets suppressed, confirming the spin insulating character of a superfluid. Our observations document the breakdown of universal conductance quantization as many-body correlations appear. The observed anomalous quantization challenges a Fermi liquid description of the normal phase, shedding new light on the nature of the strongly attractive Fermi gas. PMID- 27357669 TI - Temporal and intrinsic factors of rifampicin tolerance in mycobacteria. AB - Mycobacteria grow and divide asymmetrically, creating variability in growth pole age, growth properties, and antibiotic susceptibilities. Here, we investigate the importance of growth pole age and other growth properties in determining the spectrum of responses of Mycobacterium smegmatis to challenge with rifampicin. We used a combination of live-cell microscopy and modeling to prospectively identify subpopulations with altered rifampicin susceptibility. We found two subpopulations that had increased susceptibility. At the initiation of treatment, susceptible cells were either small and at early stages of the cell cycle, or large and in later stages of their cell cycle. In contrast to this temporal window of susceptibility, tolerance was associated with factors inherited at division: long birth length and mature growth poles. Thus, rifampicin response is complex and due to a combination of differences established from both asymmetric division and the timing of treatment relative to cell birth. PMID- 27357671 TI - Case for fMRI data repositories. PMID- 27357670 TI - Neighboring genes for DNA-binding proteins rescue male sterility in Drosophila hybrids. AB - Crosses between closely related animal species often result in male hybrids that are sterile, and the molecular and functional basis of genetic factors for hybrid male sterility is of great interest. Here, we report a molecular and functional analysis of HMS1, a region of 9.2 kb in chromosome 3 of Drosophila mauritiana, which results in virtually complete hybrid male sterility when homozygous in the genetic background of sibling species Drosophila simulans. The HMS1 region contains two strong candidate genes for the genetic incompatibility, agt and Taf1 Both encode unrelated DNA-binding proteins, agt for an alkyl-cysteine-S alkyltransferase and Taf1 for a subunit of transcription factor TFIID that serves as a multifunctional transcriptional regulator. The contribution of each gene to hybrid male sterility was assessed by means of germ-line transformation, with constructs containing complete agt and Taf1 genomic sequences as well as various chimeric constructs. Both agt and Taf1 contribute about equally to HMS1 hybrid male sterility. Transgenes containing either locus rescue sterility in about one half of the males, and among fertile males the number of offspring is in the normal range. This finding suggests compensatory proliferation of the rescued, nondysfunctional germ cells. Results with chimeric transgenes imply that the hybrid incompatibilities result from interactions among nucleotide differences residing along both agt and Taf1 Our results challenge a number of preliminary generalizations about the molecular and functional basis of hybrid male sterility, and strongly reinforce the role of DNA-binding proteins as a class of genes contributing to the maintenance of postzygotic reproductive isolation. PMID- 27357672 TI - Dynamic X-ray diffraction observation of shocked solid iron up to 170 GPa. AB - Investigation of the iron phase diagram under high pressure and temperature is crucial for the determination of the composition of the cores of rocky planets and for better understanding the generation of planetary magnetic fields. Here we present X-ray diffraction results from laser-driven shock-compressed single crystal and polycrystalline iron, indicating the presence of solid hexagonal close-packed iron up to pressure of at least 170 GPa along the principal Hugoniot, corresponding to a temperature of 4,150 K. This is confirmed by the agreement between the pressure obtained from the measurement of the iron volume in the sample and the inferred shock strength from velocimetry deductions. Results presented in this study are of the first importance regarding pure Fe phase diagram probed under dynamic compression and can be applied to study conditions that are relevant to Earth and super-Earth cores. PMID- 27357674 TI - Antibodies in multiple sclerosis oligoclonal bands target debris. PMID- 27357673 TI - Algorithmic methods to infer the evolutionary trajectories in cancer progression. AB - The genomic evolution inherent to cancer relates directly to a renewed focus on the voluminous next-generation sequencing data and machine learning for the inference of explanatory models of how the (epi)genomic events are choreographed in cancer initiation and development. However, despite the increasing availability of multiple additional -omics data, this quest has been frustrated by various theoretical and technical hurdles, mostly stemming from the dramatic heterogeneity of the disease. In this paper, we build on our recent work on the "selective advantage" relation among driver mutations in cancer progression and investigate its applicability to the modeling problem at the population level. Here, we introduce PiCnIc (Pipeline for Cancer Inference), a versatile, modular, and customizable pipeline to extract ensemble-level progression models from cross sectional sequenced cancer genomes. The pipeline has many translational implications because it combines state-of-the-art techniques for sample stratification, driver selection, identification of fitness-equivalent exclusive alterations, and progression model inference. We demonstrate PiCnIc's ability to reproduce much of the current knowledge on colorectal cancer progression as well as to suggest novel experimentally verifiable hypotheses. PMID- 27357675 TI - Influence of ammonia oxidation rate on thaumarchaeal lipid composition and the TEX86 temperature proxy. AB - Archaeal membrane lipids known as glycerol dibiphytanyl glycerol tetraethers (GDGTs) are the basis of the TEX86 paleotemperature proxy. Because GDGTs preserved in marine sediments are thought to originate mainly from planktonic, ammonia-oxidizing Thaumarchaeota, the basis of the correlation between TEX86 and sea surface temperature (SST) remains unresolved: How does TEX86 predict surface temperatures, when maximum thaumarchaeal activity occurs below the surface mixed layer and TEX86 does not covary with in situ growth temperatures? Here we used isothermal studies of the model thaumarchaeon Nitrosopumilus maritimus SCM1 to investigate how GDGT composition changes in response to ammonia oxidation rate. We used continuous culture methods to avoid potential confounding variables that can be associated with experiments in batch cultures. The results show that the ring index scales inversely (R(2) = 0.82) with ammonia oxidation rate (phi), indicating that GDGT cyclization depends on available reducing power. Correspondingly, the TEX86 ratio decreases by an equivalent of 5.4 degrees C of calculated temperature over a 5.5 fmol.cell(-1).d(-1) increase in phi. This finding reconciles other recent experiments that have identified growth stage and oxygen availability as variables affecting TEX86 Depth profiles from the marine water column show minimum TEX86 values at the depth of maximum nitrification rates, consistent with our chemostat results. Our findings suggest that the TEX86 signal exported from the water column is influenced by the dynamics of ammonia oxidation. Thus, the global TEX86-SST calibration potentially represents a composite of regional correlations based on nutrient dynamics and global correlations based on archaeal community composition and temperature. PMID- 27357677 TI - Direct calorimetric verification of thermodynamic instability of lead halide hybrid perovskites. AB - Hybrid perovskites, especially methylammonium lead iodide (MAPbI3), exhibit excellent solar power conversion efficiencies. However, their application is plagued by poor chemical and structural stability. Using direct calorimetric measurement of heats of formation, MAPbI3 is shown to be thermodynamically unstable with respect to decomposition to lead iodide and methylammonium iodide, even in the absence of ambient air or light or heat-induced defects, thus limiting its long-term use in devices. The formation enthalpy from binary halide components becomes less favorable in the order MAPbCl3, MAPbBr3, MAPbI3, with only the chloride having a negative heat of formation. Optimizing the geometric match of constituents as measured by the Goldschmidt tolerance factor provides a potentially quantifiable thermodynamic guide for seeking chemical substitutions to enhance stability. PMID- 27357676 TI - Gpr161 anchoring of PKA consolidates GPCR and cAMP signaling. AB - Scaffolding proteins organize the information flow from activated G protein coupled receptors (GPCRs) to intracellular effector cascades both spatially and temporally. By this means, signaling scaffolds, such as A-kinase anchoring proteins (AKAPs), compartmentalize kinase activity and ensure substrate selectivity. Using a phosphoproteomics approach we identified a physical and functional connection between protein kinase A (PKA) and Gpr161 (an orphan GPCR) signaling. We show that Gpr161 functions as a selective high-affinity AKAP for type I PKA regulatory subunits (RI). Using cell-based reporters to map protein protein interactions, we discovered that RI binds directly and selectively to a hydrophobic protein-protein interaction interface in the cytoplasmic carboxyl terminal tail of Gpr161. Furthermore, our data demonstrate that a binary complex between Gpr161 and RI promotes the compartmentalization of Gpr161 to the plasma membrane. Moreover, we show that Gpr161, functioning as an AKAP, recruits PKA RI to primary cilia in zebrafish embryos. We also show that Gpr161 is a target of PKA phosphorylation, and that mutation of the PKA phosphorylation site affects ciliary receptor localization. Thus, we propose that Gpr161 is itself an AKAP and that the cAMP-sensing Gpr161:PKA complex acts as cilium-compartmentalized signalosome, a concept that now needs to be considered in the analyzing, interpreting, and pharmaceutical targeting of PKA-associated functions. PMID- 27357678 TI - Mnemonic convergence in social networks: The emergent properties of cognition at a collective level. AB - The development of shared memories, beliefs, and norms is a fundamental characteristic of human communities. These emergent outcomes are thought to occur owing to a dynamic system of information sharing and memory updating, which fundamentally depends on communication. Here we report results on the formation of collective memories in laboratory-created communities. We manipulated conversational network structure in a series of real-time, computer-mediated interactions in fourteen 10-member communities. The results show that mnemonic convergence, measured as the degree of overlap among community members' memories, is influenced by both individual-level information-processing phenomena and by the conversational social network structure created during conversational recall. By studying laboratory-created social networks, we show how large-scale social phenomena (i.e., collective memory) can emerge out of microlevel local dynamics (i.e., mnemonic reinforcement and suppression effects). The social-interactionist approach proposed herein points to optimal strategies for spreading information in social networks and provides a framework for measuring and forging collective memories in communities of individuals. PMID- 27357679 TI - Sleeping Beauty screen reveals Pparg activation in metastatic prostate cancer. AB - Prostate cancer (CaP) is the most common adult male cancer in the developed world. The paucity of biomarkers to predict prostate tumor biology makes it important to identify key pathways that confer poor prognosis and guide potential targeted therapy. Using a murine forward mutagenesis screen in a Pten-null background, we identified peroxisome proliferator-activated receptor gamma (Pparg), encoding a ligand-activated transcription factor, as a promoter of metastatic CaP through activation of lipid signaling pathways, including up regulation of lipid synthesis enzymes [fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), ATP citrate lyase (ACLY)]. Importantly, inhibition of PPARG suppressed tumor growth in vivo, with down-regulation of the lipid synthesis program. We show that elevated levels of PPARG strongly correlate with elevation of FASN in human CaP and that high levels of PPARG/FASN and PI3K/pAKT pathway activation confer a poor prognosis. These data suggest that CaP patients could be stratified in terms of PPARG/FASN and PTEN levels to identify patients with aggressive CaP who may respond favorably to PPARG/FASN inhibition. PMID- 27357680 TI - Visualizing in situ translational activity for identifying and sorting slow growing archaeal-bacterial consortia. AB - To understand the biogeochemical roles of microorganisms in the environment, it is important to determine when and under which conditions they are metabolically active. Bioorthogonal noncanonical amino acid tagging (BONCAT) can reveal active cells by tracking the incorporation of synthetic amino acids into newly synthesized proteins. The phylogenetic identity of translationally active cells can be determined by combining BONCAT with rRNA-targeted fluorescence in situ hybridization (BONCAT-FISH). In theory, BONCAT-labeled cells could be isolated with fluorescence-activated cell sorting (BONCAT-FACS) for subsequent genetic analyses. Here, in the first application, to our knowledge, of BONCAT-FISH and BONCAT-FACS within an environmental context, we probe the translational activity of microbial consortia catalyzing the anaerobic oxidation of methane (AOM), a dominant sink of methane in the ocean. These consortia, which typically are composed of anaerobic methane-oxidizing archaea (ANME) and sulfate-reducing bacteria, have been difficult to study due to their slow in situ growth rates, and fundamental questions remain about their ecology and diversity of interactions occurring between ANME and associated partners. Our activity correlated analyses of >16,400 microbial aggregates provide the first evidence, to our knowledge, that AOM consortia affiliated with all five major ANME clades are concurrently active under controlled conditions. Surprisingly, sorting of individual BONCAT-labeled consortia followed by whole-genome amplification and 16S rRNA gene sequencing revealed previously unrecognized interactions of ANME with members of the poorly understood phylum Verrucomicrobia This finding, together with our observation that ANME-associated Verrucomicrobia are found in a variety of geographically distinct methane seep environments, suggests a broader range of symbiotic relationships within AOM consortia than previously thought. PMID- 27357681 TI - Analyzing the electrogenicity of cytochrome c oxidase. AB - Measurements of voltage changes in response to charge separation within membrane proteins can offer fundamental information on spectroscopically "invisible" steps. For example, results from studies of voltage changes associated with electron and proton transfer in cytochrome c oxidase could, in principle, be used to discriminate between different theoretical models describing the molecular mechanism of proton pumping. Earlier analyses of data from these measurements have been based on macroscopic considerations that may not allow for exploring the actual molecular mechanisms. Here, we have used a coarse-grained model describing the relation between observed voltage changes and specific charge transfer reactions, which includes an explicit description of the membrane, the electrolytes, and the electrodes. The results from these calculations offer mechanistic insights at the molecular level. Our main conclusion is that previously assumed mechanistic evidence that was based on electrogenic measurements is not unique. However, the ability of our calculations to obtain reliable voltage changes means that we have a tool that can be used to describe a wide range of electrogenic charge transfers in channels and transporters, by combining voltage measurements with other experiments and simulations to analyze new mechanistic proposals. PMID- 27357682 TI - Htm1p-Pdi1p is a folding-sensitive mannosidase that marks N-glycoproteins for ER associated protein degradation. AB - Our understanding of how the endoplasmic reticulum (ER)-associated protein degradation (ERAD) machinery efficiently targets terminally misfolded proteins while avoiding the misidentification of nascent polypeptides and correctly folded proteins is limited. For luminal N-glycoproteins, demannosylation of their N glycan to expose a terminal alpha1,6-linked mannose is necessary for their degradation via ERAD, but whether this modification is specific to misfolded proteins is unknown. Here we report that the complex of the mannosidase Htm1p and the protein disulfide isomerase Pdi1p (Htm1p-Pdi1p) acts as a folding-sensitive mannosidase for catalyzing this first committed step in Saccharomyces cerevisiae We reconstitute this step in vitro with Htm1p-Pdi1p and model glycoprotein substrates whose structural states we can manipulate. We find that Htm1p-Pdi1p is a glycoprotein-specific mannosidase that preferentially targets nonnative glycoproteins trapped in partially structured states. As such, Htm1p-Pdi1p is suited to act as a licensing factor that monitors folding in the ER lumen and preferentially commits glycoproteins trapped in partially structured states for degradation. PMID- 27357683 TI - Macronutrient ratios in pollen shape bumble bee (Bombus impatiens) foraging strategies and floral preferences. AB - To fuel their activities and rear their offspring, foraging bees must obtain a sufficient quality and quantity of nutritional resources from a diverse plant community. Pollen is the primary source of proteins and lipids for bees, and the concentrations of these nutrients in pollen can vary widely among host-plant species. Therefore we hypothesized that foraging decisions of bumble bees are driven by both the protein and lipid content of pollen. By successively reducing environmental and floral cues, we analyzed pollen-foraging preferences of Bombus impatiens in (i) host-plant species, (ii) pollen isolated from these host-plant species, and (iii) nutritionally modified single-source pollen diets encompassing a range of protein and lipid concentrations. In our semifield experiments, B impatiens foragers exponentially increased their foraging rates of pollen from plant species with high protein:lipid (P:L) ratios; the most preferred plant species had the highest ratio (~4.6:1). These preferences were confirmed in cage studies where, in pairwise comparisons in the absence of other floral cues, B impatiens workers still preferred pollen with higher P:L ratios. Finally, when presented with nutritionally modified pollen, workers were most attracted to pollen with P:L ratios of 5:1 and 10:1, but increasing the protein or lipid concentration (while leaving ratios intact) reduced attraction. Thus, macronutritional ratios appear to be a primary factor driving bee pollen-foraging behavior and may explain observed patterns of host-plant visitation across the landscape. The nutritional quality of pollen resources should be taken into consideration when designing conservation habitats supporting bee populations. PMID- 27357685 TI - Reply to Adamo, Key et al., and Schilling and Cruse: Crawling around the hard problem of consciousness. PMID- 27357684 TI - Cluster failure: Why fMRI inferences for spatial extent have inflated false positive rates. AB - The most widely used task functional magnetic resonance imaging (fMRI) analyses use parametric statistical methods that depend on a variety of assumptions. In this work, we use real resting-state data and a total of 3 million random task group analyses to compute empirical familywise error rates for the fMRI software packages SPM, FSL, and AFNI, as well as a nonparametric permutation method. For a nominal familywise error rate of 5%, the parametric statistical methods are shown to be conservative for voxelwise inference and invalid for clusterwise inference. Our results suggest that the principal cause of the invalid cluster inferences is spatial autocorrelation functions that do not follow the assumed Gaussian shape. By comparison, the nonparametric permutation test is found to produce nominal results for voxelwise as well as clusterwise inference. These findings speak to the need of validating the statistical methods being used in the field of neuroimaging. PMID- 27357686 TI - Stereoisomerism, crystal structures, and dynamics of belt-shaped cyclonaphthylenes. AB - The chemistry of a belt-shaped cyclic array of aromatic panels, a so-called "nanohoop," has increasingly attracted much interest, partly because it serves as a segmental model of single-wall carbon nanotubes with curved sp(2)-carbon networks. Although the unique molecular structure of nanohoops is expected to deepen our understanding in curved pi-systems, its structural chemistry is still in its infancy despite structural variants rapidly accumulated over the past several years. For instance, structural characteristics that endow the belt shapes with rigidity, an important structural feature relevant to carbon nanotubes, have not been clarified to date. We herein report the synthesis and structures of a series of belt-shaped cyclonaphthylenes. Random synthesis methods using three precursor units with different numbers of naphthylene panels allowed us to prepare 6 congeners consisting of 6 to 11 naphthylene panels, and relationships between the rigidity and the panel numbers, i.e., molecular structures, were investigated. Fundamental yet complicated stereoisomerism in the belt-shaped structures was disclosed by mathematical methods, and dynamics in the panel rotation was revealed by dynamic NMR studies with the aid of theoretical calculations. PMID- 27357687 TI - Mapping transcription factor interactome networks using HaloTag protein arrays. AB - Protein microarrays enable investigation of diverse biochemical properties for thousands of proteins in a single experiment, an unparalleled capacity. Using a high-density system called HaloTag nucleic acid programmable protein array (HaloTag-NAPPA), we created high-density protein arrays comprising 12,000 Arabidopsis ORFs. We used these arrays to query protein-protein interactions for a set of 38 transcription factors and transcriptional regulators (TFs) that function in diverse plant hormone regulatory pathways. The resulting transcription factor interactome network, TF-NAPPA, contains thousands of novel interactions. Validation in a benchmarked in vitro pull-down assay revealed that a random subset of TF-NAPPA validated at the same rate of 64% as a positive reference set of literature-curated interactions. Moreover, using a bimolecular fluorescence complementation (BiFC) assay, we confirmed in planta several interactions of biological interest and determined the interaction localizations for seven pairs. The application of HaloTag-NAPPA technology to plant hormone signaling pathways allowed the identification of many novel transcription factor protein interactions and led to the development of a proteome-wide plant hormone TF interactome network. PMID- 27357688 TI - Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice. AB - Gene-expression analysis studies from Schultz et al. estimate that more than 2,300 genes in the mouse genome are expressed predominantly in the male germ line. As of their 2003 publication [Schultz N, Hamra FK, Garbers DL (2003) Proc Natl Acad Sci USA 100(21):12201-12206], the functions of the majority of these testis-enriched genes during spermatogenesis and fertilization were largely unknown. Since the study by Schultz et al., functional analysis of hundreds of reproductive-tract-enriched genes have been performed, but there remain many testis-enriched genes for which their relevance to reproduction remain unexplored or unreported. Historically, a gene knockout is the "gold standard" to determine whether a gene's function is essential in vivo. Although knockout mice without apparent phenotypes are rarely published, these knockout mouse lines and their phenotypic information need to be shared to prevent redundant experiments. Herein, we used bioinformatic and experimental approaches to uncover mouse testis enriched genes that are evolutionarily conserved in humans. We then used gene disruption approaches, including Knockout Mouse Project resources (targeting vectors and mice) and CRISPR/Cas9, to mutate and quickly analyze the fertility of these mutant mice. We discovered that 54 mutant mouse lines were fertile. Thus, despite evolutionary conservation of these genes in vertebrates and in some cases in all eukaryotes, our results indicate that these genes are not individually essential for male mouse fertility. Our phenotypic data are highly relevant in this fiscally tight funding period and postgenomic age when large numbers of genomes are being analyzed for disease association, and will prevent unnecessary expenditures and duplications of effort by others. PMID- 27357689 TI - Solid tumor therapy by selectively targeting stromal endothelial cells. AB - Engineered tumor-targeted anthrax lethal toxin proteins have been shown to strongly suppress growth of solid tumors in mice. These toxins work through the native toxin receptors tumor endothelium marker-8 and capillary morphogenesis protein-2 (CMG2), which, in other contexts, have been described as markers of tumor endothelium. We found that neither receptor is required for tumor growth. We further demonstrate that tumor cells, which are resistant to the toxin when grown in vitro, become highly sensitive when implanted in mice. Using a range of tissue-specific loss-of-function and gain-of-function genetic models, we determined that this in vivo toxin sensitivity requires CMG2 expression on host derived tumor endothelial cells. Notably, engineered toxins were shown to suppress the proliferation of isolated tumor endothelial cells. Finally, we demonstrate that administering an immunosuppressive regimen allows animals to receive multiple toxin dosages and thereby produces a strong and durable antitumor effect. The ability to give repeated doses of toxins, coupled with the specific targeting of tumor endothelial cells, suggests that our strategy should be efficacious for a wide range of solid tumors. PMID- 27357690 TI - "Awake" extracorporeal membrane oxygenation (ECMO): pathophysiology, technical considerations, and clinical pioneering. AB - Venovenous extracorporeal membrane oxygenation (vv-ECMO) has been classically employed as a rescue therapy for patients with respiratory failure not treatable with conventional mechanical ventilation alone. In recent years, however, the timing of ECMO initiation has been readdressed and ECMO is often started earlier in the time course of respiratory failure. Furthermore, some centers are starting to use ECMO as a first line of treatment, i.e., as an alternative to invasive mechanical ventilation in awake, non-intubated, spontaneously breathing patients with respiratory failure ("awake" ECMO). There is a strong rationale for this type of respiratory support as it avoids several side effects related to sedation, intubation, and mechanical ventilation. However, the complexity of the patient-ECMO interactions, the difficulties related to respiratory monitoring, and the management of an awake patient on extracorporeal support together pose a major challenge for the intensive care unit staff. Here, we review the use of vv ECMO in awake, spontaneously breathing patients with respiratory failure, highlighting the pros and cons of this approach, analyzing the pathophysiology of patient-ECMO interactions, detailing some of the technical aspects, and summarizing the initial clinical experience gained over the past years. PMID- 27357691 TI - Are Bundled Payments a Viable Reimbursement Model for Revision Total Joint Arthroplasty? AB - BACKGROUND: Alternative payment models, such as the Centers for Medicare & Medicaid Services (CMS) Bundled Payment for Care Improvement (BPCI) initiative, aim to decrease overall costs for hip and knee arthroplasties. QUESTIONS/PURPOSES: We asked: (1) Is there any difference in the CMS episode-of care costs, hospital length of stay, and readmission rate from before and after implementation of our bundled-payment program? (2) Is there any difference in reimbursements and resource utilization between revision THA and TKA at our institution? (3) Are there any independent risk factors for patients with high costs who may not be appropriate for a bundled-payment system for revision total joint arthroplasty (TJA)? METHODS: Between October 2013 and March 2015, 218 patients underwent revision TKA or THA in one health system. Two hundred seventeen patients were reviewed as part of this study, and one patient with hemophilia was excluded from the analysis as an outlier. Our institution began a BPCI program for revision TJA during this study period. Patients' procedures done before January 1, 2014 at one hospital and January 1, 2015 at another hospital were not included in the bundled-care arrangement (70 revision TKAs and 56 revision THAs), whereas 50 revision TKAs and 41 revision THAs were performed under the BPCI initiative. Patient demographics, medical comorbidities, episode of-care reimbursement data derived directly from CMS, length of stay, and readmission proportions were compared between the bundled and nonbundled groups. RESULTS: Length of stay in the group that underwent surgery before the bundled care arrangement was longer than for patients whose procedures were done under the BPCI (mean 4.02 [SD, 3.0 days] versus mean 5.27 days [SD, 3.6 days]; p = 0.001). Index hospitalization reimbursement for the bundled group was less than for the nonbundled group (mean USD 17,754 [SD, USD 2741] versus mean USD 18,316 [SD, USD 4732]; p = 0.030). There was no difference, with the numbers available, in total episode-of-care CMS costs between the two groups (mean USD 38,107 [SD, USD 18,328] versus mean USD 37,851 [SD, USD 17,208]; p = 0.984). There was no difference, with the numbers available, in the total episode-of-care CMS costs between revision hip arthroplasties and revision knee arthroplasties (mean USD 38,627 [SD, USD 18,607] versus mean USD 37,414 [SD, USD 16,884]; p = 0.904). Disposition to rehabilitation (odds ratio [OR], 5.49; 95% CI, 1.97-15.15; p = 0.001), length of stay 4 days or greater (OR, 3.66; 95% CI, 1.60-8.38; p = 0.002), and readmission within 90 days (OR, 6.99; 95% CI, 2.58-18.91; p < 0.001) were independent risk factors for high-cost episodes. CONCLUSIONS: Bundled payments have the potential to be a viable reimbursement model for revision TJA. Owing to the unpredictable nature of the surgical procedures, inherent high risks of complications, and varying degrees of surgical complexity, future studies are needed to determine whether bundling patients having revision TJA will result in improved care and decreased costs. LEVEL OF EVIDENCE: Level IV, economic and decision analysis. PMID- 27357692 TI - Clinician and Patient-reported Outcomes Are Associated With Psychological Factors in Patients With Chronic Shoulder Pain. AB - BACKGROUND: Validated clinician outcome scores are considered less associated with psychosocial factors than patient-reported outcome measurements (PROMs). This belief may lead to misconceptions if both instruments are related to similar factors. QUESTIONS: We asked: In patients with chronic shoulder pain, what biopsychosocial factors are associated (1) with PROMs, and (2) with clinician rated outcome measurements? METHODS: All new patients between the ages of 18 and 65 with chronic shoulder pain from a unilateral shoulder injury admitted to a Swiss rehabilitation teaching hospital between May 2012 and January 2015 were screened for potential contributing biopsychosocial factors. During the study period, 314 patients were screened, and after applying prespecified criteria, 158 patients were evaluated. The median symptom duration was 9 months (interquartile range, 5.5-15 months), and 72% of the patients (114 patients) had rotator cuff tears, most of which were work injuries (59%, 93 patients) and were followed for a mean of 31.6 days (SD, 7.5 days). Exclusion criteria were concomitant injuries in another location, major or minor upper limb neuropathy, and inability to understand the validated available versions of PROMs. The PROMs were the DASH, the Brief Pain Inventory, and the Patient Global Impression of Change, before and after treatment (physiotherapy, cognitive therapy and vocational training). The Constant-Murley score was used as a clinician-rated outcome measurement. Statistical models were used to estimate associations between biopsychosocial factors and outcomes. RESULTS: Greater disability on the DASH was associated with psychological factors (Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale combined coefficient, 0.64; 95% CI, 0.25-1.03; p = 0.002) and social factors (language, professional qualification combined coefficient, 6.15; 95% CI, -11.09 to -1.22; p = 0.015). Greater pain on the Brief Pain Inventory was associated with psychological factors (Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale combined coefficient, 0.076; 95% CI, 0.021-0.13; p = 0.006). Poorer impression of change was associated with psychological factors (Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, Tampa Scale of Kinesiophobia coefficient, 0.93; 95% CI, 0.87-0.99; p = 0.026) and social factors (education, language, and professional qualification coefficient, 6.67; 95% CI, 2.77-16.10; p < 0.001). Worse clinician rated outcome was associated only with psychological factors (Hospital Anxiety and Depression Scale (depression only), Pain Catastrophizing Scale, Tampa Scale of Kinesiophobia combined coefficient, -0.35; 95% CI, -0.58 to -0.12; p = 0.003). CONCLUSIONS: Depressive symptoms and catastrophizing appear to be key factors influencing PROMs and clinician-rated outcomes. This study suggests revisiting the Constant-Murley score. LEVEL OF EVIDENCE: Level III, prognostic study. PMID- 27357693 TI - VarElect: the phenotype-based variation prioritizer of the GeneCards Suite. AB - BACKGROUND: Next generation sequencing (NGS) provides a key technology for deciphering the genetic underpinnings of human diseases. Typical NGS analyses of a patient depict tens of thousands non-reference coding variants, but only one or very few are expected to be significant for the relevant disorder. In a filtering stage, one employs family segregation, rarity in the population, predicted protein impact and evolutionary conservation as a means for shortening the variation list. However, narrowing down further towards culprit disease genes usually entails laborious seeking of gene-phenotype relationships, consulting numerous separate databases. Thus, a major challenge is to transition from the few hundred shortlisted genes to the most viable disease-causing candidates. RESULTS: We describe a novel tool, VarElect ( http://ve.genecards.org ), a comprehensive phenotype-dependent variant/gene prioritizer, based on the widely used GeneCards, which helps rapidly identify causal mutations with extensive evidence. The GeneCards suite offers an effective and speedy alternative, whereby >120 gene-centric automatically-mined data sources are jointly available for the task. VarElect cashes on this wealth of information, as well as on GeneCards' powerful free-text Boolean search and scoring capabilities, proficiently matching variant-containing genes to submitted disease/symptom keywords. The tool also leverages the rich disease and pathway information of MalaCards, the human disease database, and PathCards, the unified pathway (SuperPaths) database, both within the GeneCards Suite. The VarElect algorithm infers direct as well as indirect links between genes and phenotypes, the latter benefitting from GeneCards' diverse gene-to-gene data links in GenesLikeMe. Finally, our tool offers an extensive gene-phenotype evidence portrayal ("MiniCards") and hyperlinks to the parent databases. CONCLUSIONS: We demonstrate that VarElect compares favorably with several often-used NGS phenotyping tools, thus providing a robust facility for ranking genes, pointing out their likelihood to be related to a patient's disease. VarElect's capacity to automatically process numerous NGS cases, either in stand-alone format or in VCF-analyzer mode (TGex and VarAnnot), is indispensable for emerging clinical projects that involve thousands of whole exome/genome NGS analyses. PMID- 27357694 TI - Genomic prediction of host resistance to sea lice in farmed Atlantic salmon populations. AB - BACKGROUND: Sea lice have significant negative economic and welfare impacts on marine Atlantic salmon farming. Since host resistance to sea lice has a substantial genetic component, selective breeding can contribute to control of lice. Genomic selection uses genome-wide marker information to predict breeding values, and can achieve markedly higher accuracy than pedigree-based methods. Our aim was to assess the genetic architecture of host resistance to sea lice, and test the utility of genomic prediction of breeding values. Individual lice counts were measured in challenge experiments using two large Atlantic salmon post-smolt populations from a commercial breeding programme, which had genotypes for ~33 K single nucleotide polymorphisms (SNPs). The specific objectives were to: (i) estimate the heritability of host resistance; (ii) assess its genetic architecture by performing a genome-wide association study (GWAS); (iii) assess the accuracy of predicted breeding values using varying SNP densities (0.5 to 33 K) and compare it to that of pedigree-based prediction; and (iv) evaluate the accuracy of prediction in closely and distantly related animals. RESULTS: Heritability of host resistance was significant (0.22 to 0.33) in both populations using either pedigree or genomic relationship matrices. The GWAS suggested that lice resistance is a polygenic trait, and no genome-wide significant quantitative trait loci were identified. Based on cross-validation analysis, genomic predictions were more accurate than pedigree-based predictions for both populations. Although prediction accuracies were highest when closely related animals were used in the training and validation sets, the benefit of having genomic-versus pedigree-based predictions within a population increased as the relationships between training and validation sets decreased. Prediction accuracy reached an asymptote with a SNP density of ~5 K within populations, although higher SNP density was advantageous for cross-population prediction. CONCLUSIONS: Host resistance to sea lice in farmed Atlantic salmon has a significant genetic component. Phenotypes relating to host resistance can be predicted with moderate to high accuracy within populations, with a major advantage of genomic over pedigree-based methods, even at relatively sparse SNP densities. Prediction accuracies across populations were low, but improved with higher marker densities. Genomic selection can contribute to lice control in salmon farming. PMID- 27357695 TI - Community perceptions of pre-eclampsia and eclampsia in Ogun State, Nigeria: a qualitative study. AB - BACKGROUND: Pre-eclampsia is a complication of pregnancy responsible for high rates of morbidity and mortality, particularly in sub-Saharan Africa. When undetected or poorly managed, it may progress to eclampsia which further worsens the prognosis. While most studies examining pre-eclampsia have used a bio-medical model, this study recognizes the role of the socio-cultural environment, in order to understand perceptions of pre-eclampsia within the community. METHODS: The study was conducted in Ogun State, Nigeria in 2011-2012. Data were obtained through twenty-eight focus group discussions; seven with pregnant women (N = 80), eight with new mothers (N = 95), three with male decision-makers (N = 35), six with community leaders (N = 68), and three with traditional birth attendants (N = 36). Interviews were also conducted with the heads of the local traditional birth attendants (N = 4) and with community leaders (N = 5). Data were transcribed verbatim and analysed in NVivo 10 software. RESULTS: There was no terminology reportedly used for pre-eclampsia in the native language - Yoruba; however, hypertension has several terms independent of pregnancy status. Generally, 'giri alaboyun' describes seizures specific to pregnancy. The cause of hypertension in pregnancy was thought to be due to depressive thoughts as a result of marital conflict and financial worries, while seizures in pregnancy were perceived to result from prolonged exposure to cold. There seemed to be no traditional treatment for hypertension. However for seizures the use of herbs, concoctions, incisions, and topical application of black soap were widespread. CONCLUSION: This study illustrates that knowledge of pre-eclampsia and eclampsia are limited amongst communities of Ogun State, Nigeria. Findings reveal that pre-eclampsia was perceived as a stress-induced condition, while eclampsia was perceived as a product of prolonged exposure to cold. Thus, heat-related local medicines and herbal concoctions were the treatment options. Perceptions anchored on cultural values and lack of adequate and focused public health awareness is a major constraint to knowledge of the aetiology and treatment of the conditions. A holistic approach is recommended for sensitization at the community level and the need to change the community perceptions of pre-eclampsia remains a challenge. TRIAL REGISTRATION: NCT01911494 . PMID- 27357696 TI - The Influence of Infant Feeding Practices on Infant Mortality in Southern Africa. AB - Objective To examine the adjusted and unadjusted effects of infant feeding practices on infant mortality in Southern Africa. Methods A merged dataset from the most recent Demographic and Health Surveys for Lesotho, Swaziland, Zambia and Zimbabwe was analysed using the Cox Proportional Hazard Model. A total number of 13,218 infants born in 5 years preceding all the surveys with information on infant feeding practices constituted the study population. Infant mortality was the outcome variable and infant feeding practices categorised into; no breastfeeding, partial breastfeeding and exclusive breastfeeding were the main explanatory variables. Maternal demographic and socio-economic characteristics and infants' bio-demographic characteristics were also studied. Results Although, exclusive breastfeeding was quite low (12 %), exclusively breastfed infants exhibited a 97 % lower risk of dying during infancy compared to infants not breastfed in the region. Variations existed by country in the levels and patterns of both infant mortality and infant feeding practices. Mother's country, highest level of education and marital status; child's sex, birth weight and preceding birth interval were the significant predictors of infant mortality in Southern Africa. Conclusions Any form of breastfeeding whether exclusive or partial breastfeeding greatly reduces the risk of infant mortality with the greatest mortality reduction effect observed among exclusively breastfed infants in Southern Africa. To reduce the upsurge of infant mortality, there is the need to step up the effectiveness of child nutrition programmes that promote breastfeeding and put emphasis on exclusive breastfeeding of infants in the region. PMID- 27357697 TI - Postpartum Health Services Requested by Mothers with Newborns Receiving Intensive Care. AB - Objectives Our pilot study aimed to build knowledge of the postpartum health needs of mothers with infants in a newborn intensive care unit (NICU). Methods Between May 2008 and December 2009, a Certified Nurse Midwife was available during workday hours to provide health care services to mothers visiting their infants in the NICU at a large tertiary care center. Results A total of 424 health service encounters were recorded. Maternal requests for services covered a wide variety of needs, with primary care being the most common. Key health concerns included blood pressure monitoring, colds, coughs, sore throats, insomnia and migraines. Mothers also expressed a need for mental health assessment and support, obstetric care, treatment for sexually transmitted infections, tobacco cessation, breastfeeding assistance, postpartum visits, and provision of contraception. Conclusions Our study suggests that mothers with babies in the NICU have a host of health needs. We also found that women were receptive to receiving health services in a critical care pediatric setting. Intensive care nurseries could feasibly partner with in-patient mother-baby units and/or on-site obstetric clinics to increase access to health care for the mothers of the high-risk newborns in their units. Modifications should be made within health care systems that serve high-risk infants to better address the many needs of the mother/baby dyad in the postpartum period. PMID- 27357698 TI - The bulk of the hematopoietic stem cell population is dispensable for murine steady-state and stress hematopoiesis. AB - Long-term repopulating (LT) hematopoietic stem cells (HSCs) are the most undifferentiated cells at the top of the hematopoietic hierarchy. The regulation of HSC pool size and its contribution to hematopoiesis are incompletely understood. We depleted hematopoietic stem and progenitor cells (HSPCs) in adult mice in situ and found that LT-HSCs recovered from initially very low levels (<1%) to below 10% of normal numbers but not more, whereas progenitor cells substantially recovered shortly after depletion. In spite of the persistent and massive reduction of LT-HSCs, steady-state hematopoiesis was unaffected and residual HSCs remained quiescent. Hematopoietic stress, although reported to recruit quiescent HSCs into cycle, was well tolerated by HSPC-depleted mice and did not induce expansion of the small LT-HSC compartment. Only upon 5 fluorouracil treatment was HSPC-depleted bone marrow compromised in reconstituting hematopoiesis, demonstrating that HSCs and early progenitors are crucial to compensate myeloablation. Hence, a contracted HSC compartment cannot recover in situ to its original size, and normal steady-state blood cell generation is sustained with <10% of normal LT-HSC numbers without increased contribution of the few residual cells. PMID- 27357700 TI - Hospital volume and acute myeloid leukemia mortality in Medicare beneficiaries aged 65 years and older. PMID- 27357699 TI - Vascular thiol isomerases. AB - Thiol isomerases are multifunctional enzymes that influence protein structure via their oxidoreductase, isomerase, and chaperone activities. These enzymes localize at high concentrations in the endoplasmic reticulum of all eukaryotic cells where they serve an essential function in folding nascent proteins. However, thiol isomerases can escape endoplasmic retention and be secreted and localized on plasma membranes. Several thiol isomerases including protein disulfide isomerase, ERp57, and ERp5 are secreted by and localize to the membranes of platelets and endothelial cells. These vascular thiol isomerases are released following vessel injury and participate in thrombus formation. Although most of the activities of vascular thiol isomerases that contribute to thrombus formation are yet to be defined at the molecular level, allosteric disulfide bonds that are modified by thiol isomerases have been described in substrates such as alphaIIbbeta3, alphavbeta3, GPIbalpha, tissue factor, and thrombospondin. Vascular thiol isomerases also act as redox sensors. They respond to the local redox environment and influence S-nitrosylation of surface proteins on platelets and endothelial cells. Despite our rudimentary understanding of the mechanisms by which thiol isomerases control vascular function, the clinical utility of targeting them in thrombotic disorders is already being explored in clinical trials. PMID- 27357702 TI - Distal longitudinal deformation of a Synergy stent by jailed Rotawire guidewire. AB - Recent advances in stent technology have led to the development of thin strut platforms with fewer connectors. This has improved delivery but compromised strength, as illustrated by recent cases of longitudinal compression. We present an unusual case of longitudinal shortening at the distal end of a Synergy stent. PMID- 27357701 TI - The level of embryonation influences detection of Ostertagia ostertagi eggs by semi-quantitative PCR. AB - BACKGROUND: The Internal Transcribed Spacer 2 (ITS2) is a candidate diagnostic marker of the pathogenic cattle nematode Ostertagia ostertagi. The aims of this study were: (i) to document and quantify how the development of O. ostertagi eggs affects ITS2 copies under different storage conditions, and (ii) to suggest optimal storage conditions for faecal samples in a diagnostic pipeline that involves detection and semi-quantification by real-time semi-quantitative polymerase chain reaction (qPCR). FINDINGS: Eggs of Ostertagia ostertagi were obtained from fresh faeces and stored at 4 degrees C or 25 degrees C under aerobic or anaerobic (vacuum packing) conditions. Development was monitored by microscopy for up to 336 h, and the ITS2 copies were determined by qPCR from a fixed number of parasites. Under aerobic conditions at 25 degrees C, embryonation and a significant increase of ITS2 copies (P < 0.0001) were observed after 12 h. At 4 degrees C, embryonation occurred after 168 h with a trend towards increased ITS2 copies. Anaerobic conditions inhibited egg development at both temperatures and no significant increase in ITS2 copies was noticed (P = 0.90). ITS2 copies were analysed for each parasite stage: first-stage larvae (L1) exhibited significantly higher copy numbers (20,353 +/- 1,950) than unembryonated eggs (568 +/- 168; P < 0.0001) with lower coefficient of variation (33 vs 266 %). CONCLUSIONS: Aerobic storage of O. ostertagi eggs at 25 degrees C led to a significant increase in ITS2 copies after 12 h due to embryonation and subsequent hatching. In contrast, anaerobic storage (vacuum packing) at 25 degrees C completely inhibited egg development and any undesirable semi-quantification bias for up to 336 h. Hence, vacuum packing is an optimal storage strategy prior to molecular diagnostic analyses. Alternatively, aerobic storage at 4 degrees C for up to 72 h can be used. Due to high copy numbers and lower genetic variation, the L1 stage may be considered for diagnostics and further molecular research. PMID- 27357703 TI - Innovative sensory methods to access acceptability of mixed polymer semisoft ovules for microbicide applications. AB - Vaginal microbicides are a promising means to prevent the transmission of HIV, empowering women by putting protection under their control. We have been using gel technology to develop microbicides in the intermediate texture space to overcome shortcomings of current solid and liquid forms. We recently formulated semisoft ovules from mixed polymer combinations of carrageenan and Carbopol 940P to overcome some of the flaws with our previous generation of formulations based solely on carrageenan. To determine the user acceptability of the reformulated gels, women first evaluated intact semisoft ovules before evaluating ovules that had been subjected to mechanical crushing to simulate samples that represent post use discharge. Women then evaluated combinations of intact and discharge samples to understand how ovule textures correlated with texture of the resulting discharge samples. Carbopol concentration directly and inversely correlated with willingness to try for discharge samples and intact samples, respectively. When evaluating intact samples, women focused on the ease of inserting the product and preferred firmer samples; conversely, when evaluating discharge samples, softer samples that resulted in a smooth paste were preferred. Significant differences between samples were lost when evaluating pairs as women made varying trade-offs between their preference for ease of inserting intact ovules and acceptability of discharge appearance. Evaluating samples that represent different stages of the use cycle reveals a more holistic measure of product acceptability. Studying sensory acceptability in parallel with biophysical performance enables an iterative design process that considers what women prefer in terms of insertion as well as possibility of leakage. PMID- 27357704 TI - Site-specific bacterial chromosome engineering mediated by IntA integrase from Rhizobium etli. AB - BACKGROUND: The bacterial chromosome may be used to stably maintain foreign DNA in the mega-base range. Integration into the chromosome circumvents issues such as plasmid replication, stability, incompatibility, and copy number variance. The site-specific integrase IntA from Rhizobium etli CFN42 catalyzes a direct recombination between two specific DNA sites: attA and attD (23 bp). This recombination is stable. The aim of this work was to develop a R. etli derivative that may be used as recipient for the integration of foreign DNA in the chromosome, adapting the IntA catalyzed site-specific recombination system. RESULTS: To fulfill our aim, we designed a Rhizobium etli CFN42 derivative, containing a "landing pad" (LP) integrated into the chromosome. The LP sector consists of a green fluorescent protein gene under the control of the lacZ promoter and a spectinomycin resistance gene. Between the lacZ promoter and the GFP gene we inserted an IntA attachment site, which does not affect transcription from the lac promoter. Also, a mobilizable donor vector was generated, containing an attA site and a kanamycin resistance gene; to facilitate insertion of foreign DNA, this vector also contains a multicloning site. There are no promoters flanking the multicloning site. A biparental mating protocol was used to transfer the donor vector into the landing pad strain; insertion of the donor vector into the landing pad sector via IntA-mediated attA X attA recombination thereby interrupted the expression of the green fluorescent protein, generating site specific cointegrants. Cointegrants were easily recognized by screening for antibiotic sensitivity and lack of GFP expression, and were obtained with an efficiency of 6.18 %. CONCLUSIONS: Integration of foreign DNA in Rhizobium, lacking any similarity with the genome, can be easily achieved by IntA-mediated recombination. This protocol contains the mating and selection procedures for creating and isolating integrants. PMID- 27357705 TI - The effect of Eulaliopsis binata on the physi-chemical properties, microbial biomass, and enzymatic activities in Cd-Pb polluted soil. AB - Pot culture experiment using mining wasteland soil was carried out to study the effect of Eulaliopsis binata on the heavy-metal polluted soil with the growth of 90, 180, 270, and 360 days. Soil nutritional components, heavy metal, microbial biomass, and enzymatic activities were analyzed in this study, and the control group had no plants. The results showed that heavy metal contents decreased with E. binata growth, extractable Cd and Pb decreased 28 and 15 % after 1 year, but the difference was not significant compared with the control. While soil nutritional components, microbial biomass and enzymatic activities increased significantly as compared with the control. Comparing with pre-experiment, soil organic matter, N, P, K, microbial biomass C, N, P, invertase, urease, acid phosphatase, and catalase increased 0.9, 1.1, 3.0, 1.1, 0.4, 0.3, and 0.5 times, respectively. The indexes of soil nutritional components, microbial biomass, and enzymatic activities are positively correlated to each other, while they are negatively correlated to heavy metal content respectively. E. binata has positive influence on Cd-Pb pollution soil and broad application prospects in remediating heavy-metal polluted soil. PMID- 27357706 TI - Performance of a pilot-scale wet electrostatic precipitator for the control of sulfuric acid mist. AB - The use of a wet electrostatic precipitator (WESP) is often regarded as a viable option to reduce sulfuric acid mist emitted from the wet flue gas desulfurization (WFGD) tower in coal-fired power plants. In this study, a pilot-scale wet electrostatic precipitator equipped with a wall-cooled collection electrode is investigated for the control of sulfuric acid mist from a simulated WFGD system. The results show that due to partial charging effect, the removal efficiency of sulfuric acid aerosol decreases when the aerosol size decreases to several tens of nanometers. Moreover, due to the plasma-induced effect, a large number of ultrafine sulfuric acid aerosols below 50 nm formed at a voltage higher than 24 kV inside the WESP. The percentages of submicron-sized aerosols significantly increase together with the voltage. To minimize the adverse plasma-induced effect, a WESP should be operated at a high gas velocity with an optimum high voltage. Even at a high flue gas velocity of 2.3 m s(-1), the mass concentration and the total number concentration of uncaptured sulfuric acid aerosols at the WESP outlet are as low as ca. 0.6 mg m(-3) and ca. 10(4) 1 cm(-3) at 28 kV, respectively. The corresponding removal efficiencies were respectively higher than 99.4 and 99.9 % and are very similar to that at 1.1 and 1.6 m s(-1). Moreover, the condensation-induced aerosol growth enhances the removal of sulfuric acid mist inside a WESP and enables a low emission concentration of ca. 0.65 mg m(-3) with a corresponding removal efficiency superior to 99.4 % even at a low voltage of 21 kV, and of ca. 0.35 mg m(-3) with a corresponding removal efficiency superior to 99.6 % at a higher voltage level of 26 kV. PMID- 27357707 TI - The use of juvenile Solea solea as sentinel in the marine platform of the Ebre Delta: in vitro interaction of emerging contaminants with the liver detoxification system. AB - Juveniles of Solea solea were sampled during the spring season in three consecutive years at a marine site by the mouth of the Ebre river. The aim was to assess if the extractive works from the toxic load upstream the river could be reflected on the health status of the fish living at the immediate sea. The biomarkers selected for the in vivo field study are commonly used as indicators of chemical exposures. They include activities of energy metabolism: lactate dehydrogenase (LDH) and citrate synthase (CS); neurotoxicity: cholinesterases (ChE); xenobiotic metabolism: cytochrome P450 (CYP)-dependent: EROD and BFCOD, carboxylesterase (CbE), glutathione S-transferase (GST) and uridine diphosphate glucuronyltransferase (UDPGT); and oxidative stress parameters such as catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPX) as well as levels of lipid peroxidation (LPO). These biomarkers were mostly analysed in liver but also in gills and muscle depending on their particular tissue distribution and role. A complementary in vitro approach was also sought to see the capacity of common emerging contaminants (pharmaceuticals and personal care products; PPCPs) to interact with the liver microsomal detoxification system of the fish (EROD, BFCOD and CbE activities). The results indicated that in fish sampled in 2015 there was an enhancement in detoxification parameters (EROD, BFCOD and gill GR), muscular ChEs and gill CS, but a decrease in CbE activity and a marked oxidative stress situation (increased LPO and decreased CAT activity). Also, 4 out of the 10 PPCPs tested in vitro were able to interact with the CYP3A4 (BFCOD) enzymatic system while the lipid regulators simvastatin and fenofibrate inhibited CbE activity, as it occurs in higher vertebrates. The in vivo results support the use of a multibiomarker approach when assessing the disturbances due to chemical exposures, not only spatially but also over time, once the influence of other variables has been taken into consideration. The in vitro results highlight the importance of the CYP3A4 and CbE pathway in pharmaceutical metabolism, also in fish. PMID- 27357708 TI - Bacteria and fungi inactivation by photocatalysis under UVA irradiation: liquid and gas phase. AB - In the last decade, environmental risks associated with wastewater treatment plants (WWTPs) have become a concern in the scientific community due to the absence of specific legislation governing the occupational exposure limits (OEL) for microorganisms present in indoor air. Thus, it is necessary to develop techniques to effectively inactivate microorganisms present in the air of WWTPs facilities. In the present work, ultraviolet light A radiation was used as inactivation tool. The microbial population was not visibly reduced in the bioaerosol by ultraviolet light A (UVA) photolysis. The UVA photocatalytic process for the inactivation of microorganisms (bacteria and fungi, ATCC strains and isolates from indoor air samples of a WWTP) using titanium dioxide (TiO2 P25) and zinc oxide (ZnO) was tested in both liquid-phase and airborne conditions. In the slurry conditions at liquid phase, P25 showed a better performance in inactivation. For this reason, gas-phase assays were performed in a tubular photoreactor packed with cellulose acetate monolithic structures coated with P25. The survival rate of microorganisms under study decreased with the catalyst load and the UVA exposure time. Inactivation of fungi was slower than resistant bacteria, followed by Gram-positive bacteria and Gram-negative bacteria. Graphical abstract Inactivation of fungi and bacteria in gas phase by photocatalitic process performed in a tubular photoreactor packed with cellulose acetate monolith structures coated with TiO2. PMID- 27357710 TI - Treat the disease not the symptoms: Successful management of obsessive compulsive disorder in bipolar disorder with aripiprazole augmentation. PMID- 27357711 TI - Tibolone treatment for perimenopausal depression: Three cases. PMID- 27357709 TI - Cardiac surgery 2015 reviewed. AB - For the year 2015, almost 19,000 published references can be found in PubMed when entering the search term "cardiac surgery". The last year has been again characterized by lively discussions in the fields where classic cardiac surgery and modern interventional techniques overlap. Lacking evidence in the field of coronary revascularization with either percutaneous coronary intervention or bypass surgery has been added. As in the years before, CABG remains the gold standard for the revascularization of complex stable triple-vessel disease. Plenty of new information has been presented comparing the conventional to transcatheter aortic valve implantation (TAVI) demonstrating similar short- and mid-term outcomes at high and low risk, but even a survival advantage with transfemoral TAVI at intermediate risk. In addition, there were many relevant and interesting other contributions from the purely operative arena. This review article will summarize the most pertinent publications in the fields of coronary revascularization, surgical treatment of valve disease, heart failure (i.e., transplantation and ventricular assist devices), and aortic surgery. While the article does not have the expectation of being complete and cannot be free of individual interpretation, it provides a condensed summary that is intended to give the reader "solid ground" for up-to-date decision-making in cardiac surgery. PMID- 27357712 TI - Delusional infestation in a patient with posterior reversible encephalopathy syndrome. PMID- 27357713 TI - Behavioural addictions: A challenge for psychopathology and psychiatric nosology. AB - Disorders characterised by repetitive and problematic behaviours and poor impulse control have been increasingly conceptualised as behavioural addictions. This article examines the concept of behavioural addiction and argues that the addiction framework is only one approach to these behavioural disturbances. It cautions against a tendency to regard many activities that are performed with an extraordinary intensity or frequency and that have some negative consequences as behavioural addiction. There is a need for more research to better understand the links between repetitive and problematic behaviours and other psychopathology, as well as the function of these behaviours and factors that maintain them. PMID- 27357714 TI - Behavioural health disorders rather than behavioural addictions. PMID- 27357715 TI - Organic psychosis improving after a seizure. PMID- 27357716 TI - Anti-NR2 antibodies, blood-brain barrier, and cognitive dysfunction. AB - Cognitive dysfunction (CD) is one of the most common neuropsychiatric manifestations of systemic lupus erythematosus (SLE). In animal models, antibodies to NR2 subunit of N-methyl D-aspartate receptor (anti-NR2) cause memory impairment, but only with blood-brain barrier (BBB) disruption or intrathecal administration. Several studies have failed to find association of aNR2 with CD, but none have assessed BBB integrity. S100B, an astrocyte-specific protein, has been used as biomarker of BBB disruption in traumatic brain injury and some neurodegenerative disorders. Antibodies to this immunologically privileged protein (anti-S100B) might indicate preceding BBB disruption. We hypothesized that aNR2 antibody is pathogenic in SLE patients only with BBB disruption. Demographic, clinical, and laboratory data was collected from patients with SLE. Total throughput score (TTS) of the Automated Neuropsychological Assessment Metrics (ANAM) was used as primary outcome measure. CD was defined as TTS < 1.5 SD below an age-, sex-, and race-matched RA population mean. Serum was analyzed by established ELISA techniques. Fifty-seven patients were evaluated and 12 had CD. Age, ethnicity, and family income were significantly different between the two groups (p < 0.05). In a multiple regression model adjusting for other variables, no significant effects of anti NR2, S100B, or anti-S100B on TTS were found. Even at high levels of S100B and anti-S100B, no significant influence of anti-NR2 on TTS was found. The anti-NR2 was not associated with CD in SLE even in context of potential BBB disruption. This suggests that, if pathogenic, these antibodies may be produced intrathecally. PMID- 27357718 TI - SASDAS (simplified version of ankylosing spondylitis disease activity score)-ESR performance and development of SASDAS-CRP and their agreement with ASDAS-ESR and ASDAS-CRP in patients with ankylosing spondylitis. PMID- 27357717 TI - Nailfold capillaroscopy assessment of microcirculation abnormalities and endothelial dysfunction in children with primary or secondary Raynaud syndrome. AB - Raynaud syndrome (RS) manifests as episodes of transient spasms of peripheral blood vessels, most often in response to cold. The reason of that symptom (primary RS (pRS)) usually cannot be found but may be accompanied by some autoimmune diseases (secondary RS (sRS)). In this study, we assessed microcapillary status and serum concentrations of chosen cytokines, adhesive molecules, and nitric oxide (NO) in patients with pRS and sRS in comparison with healthy children. Eighty-six patients with RS were enrolled into the study, including 52 with pRS and 34 with sRS. The control group consisted of 29 healthy children. A decrease in myorelaxative and anticoagulant abilities was observed, with simultaneous prevalence of vasopressor substances and procoagulative activity. Therefore, several important factors such as endothelin-1 (ET-1), E selectin (E-sel), interleukin-18 (IL-18), and nitrogen oxide (NO) were also analyzed. Two types of capillaroscopy status were determined: normal and microangiopathic. There was a significant relationship between presence of microangiopathy and higher serum ET-1 (p = 0.018) and E-sel (p = 0.021) levels. Similarly, we have found a correlation between presence of ANA and higher ET-1 (p = 0.005), but not E-sel (p = 0.241). In patients with pRS, we found significant relationship between ANA and higher ET-1 (p = 0.008). No such relations were observed in sRS patients. Our data indicates that external factor-induced vasoconstrictive effects dominated in pRS, whereas in sRS in the course of connective tissue diseases, it was accompanied by coexistent vasodilation due to endothelial dysfunction. The latter phenomenon is at least partially dependent on insufficient NO release. PMID- 27357719 TI - Nuclear size measurement for distinguishing urothelial carcinomas from reactive urothelium on tissue sections. AB - BACKGROUND: Pathological diagnosis of urothelial carcinoma (UC) is primarily based on cytological atypia. It has previously been shown that high-grade (HG) UC, particularly UC in situ cells (CIS), can be over five times the size of a lymphocyte. However, this has not been demonstrated in comparison to reactive urothelium. The objective of this study was to empirically compare the difference in nuclear size of UC cells with reactive urothelial cells. METHODS: Using CellSens imaging software, we measured urothelial nuclear length (l) and width (w) on digital images of H&E sections. The area (a) of a nucleus was calculated based on the oval shape of most urothelial cells. Lymphocytes were measured to calculate normalized urothelial linear and area ratios. RESULTS: A total of 1085 urothelial cell nuclei from 60 cases were measured from reactive urothelium, low grade (LG) UC, HG UC and CIS. CIS nuclei were found to have an a 2.75 times larger than reactive nuclei (p < 0.001). A nuclear size cut-off of 11 um for l and 7 um for w was found to be sensitive [98.09 % (95 % CI: 95.60-99.38 %) and 89.31 % (95 % CI: 83.6-91.82 %) for l and w, respectively] and specific [92.60 % (95 % CI: 87.13-95.82 %) and 85.71 % (95 % CI: 79.49-90.63 %) for l and w, respectively] for distinguishing CIS from reactive atypia. CONCLUSIONS: Nuclear morphometry can be used to differentiate CIS from reactive atypia. A l over 11 um and a w over 7 um and is highly sensitive and specific for CIS compared to reactive urothelium. This difference in nuclear size may be used as a tool for differentiating the flat urothelial lesions from reactive urothelium in daily practice. PMID- 27357720 TI - Isolation and characterization of porcine epidemic diarrhea virus associated with the 2014 disease outbreak in Mexico: case report. AB - BACKGROUND: Interest in porcine epidemic diarrhea has grown since the 2013 outbreak in the United States caused major losses, with mortality rates up to 100 % in suckling piglets. In Mexico, an outbreak of porcine epidemic diarrhea, characterized by 100 % mortality in piglets, began in March 2014 in the State of Mexico. METHODS: The aim of this study was to confirm and identify porcine epidemic diarrhea virus (PEDV) in samples from piglets with suggestive clinical signs using virological, histological, and molecular techniques. Necropsy was performed on 13 piglets from two litters with initial and advanced clinical signs. Suggestive lesions of acute infection with PEDV were detected in histological sections of the small and large bowels; specifically, multiple virus particles with visible crown-shaped projections were observed using electron microscopy and negative staining. Viral isolation was performed in Vero cells with trypsin. Infection was monitored by observation of cytopathic effect, and titration was determined by TCID50/ml. The presence of the PEDV in cultures and clinical samples was confirmed by RT-PCR amplification and sequencing of a 651-bp segment of the S glycoprotein gene, as well as a 681-bp matrix protein gene. RESULTS: The nucleotide sequence analysis of the Mexican isolates showed marked homology to viruses that circulated in 2013 in Colorado, USA. CONCLUSIONS: In this paper we confirm the isolation and characterization of PEDV from animals with early and advanced clinical signs. PMID- 27357721 TI - PhyloToAST: Bioinformatics tools for species-level analysis and visualization of complex microbial datasets. AB - The 16S rRNA gene is widely used for taxonomic profiling of microbial ecosystems; and recent advances in sequencing chemistry have allowed extremely large numbers of sequences to be generated from minimal amounts of biological samples. Analysis speed and resolution of data to species-level taxa are two important factors in large-scale explorations of complex microbiomes using 16S sequencing. We present here new software, Phylogenetic Tools for Analysis of Species-level Taxa (PhyloToAST), that completely integrates with the QIIME pipeline to improve analysis speed, reduce primer bias (requiring two sequencing primers), enhance species-level analysis, and add new visualization tools. The code is free and open source, and can be accessed at http://phylotoast.org. PMID- 27357722 TI - Infective endocarditis of an aortic intimal flap due to Streptococcus agalactiae in a patient with Sjogren's syndrome: an unusual clinical case report. PMID- 27357723 TI - Bone stability around implants in elderly patients with reduced bone mineral density - a prospective study on mandibular overdentures. AB - OBJECTIVE: The purpose of this prospective clinical study was to determine whether reduced bone mineral density (BMD) is correlated with a higher risk for dental implant therapy in an elderly patient population. MATERIAL AND METHODS: Seventy-nine patients recruited at the Prince Philip Dental Hospital were provided with 2-implant-supported mandibular overdentures. Skeletal BMD was recorded before the implant therapy. The World Health Organization Osteoporosis Diagnosis Classification (femoral neck score) was utilized to define the osteoporosis status of patients. Periapical radiographs were taken with a special radiographic holder at the time of implant loading (baseline) and at follow-up examinations. The mesial and distal marginal bone levels of each implant were measured. The mean marginal bone loss (mMBL) and greatest marginal bone loss (GBL) of four implant sites at patient level were recorded for data analysis. Clinical examination including plaque score (PI) and bleeding on probing (BOP) was recorded. RESULTS: Of the 79 patients recruited in the study, the survival rate of implant was 98.7%. Sixty-three patients (79.7%) were finally available for data collection and statistical analyses. The mean follow-up time was 62.9 (SD = 15.2) months with the mean MBL 0.65 mm (SD = 0.67) and mean GBL 1.25 mm (SD = 0.83), respectively. The average BOP and PI of patients were 49.6% (SD = 30.8) and 47.4% (SD = 37.4). Only BOP was found significantly correlated with mMBL (r = 0.321, P = 0.01). Skeletal BMD was not associated with marginal bone loss (mean MBL: r = -0.094, P = 0.466; mean GBL: r = 0.04, P = 0.761). CONCLUSIONS: Within the limits of this study, osteoporosis was not a contraindication for implant therapy, and reduced skeletal BMD was not associated with increased marginal bone loss around implants or other complications in an elderly population. PMID- 27357724 TI - Ruthenium-Catalyzed C-H Alkynylation of Aromatic Amides with Hypervalent Iodine Alkyne Reagents. AB - An efficient C-H activation method for the ortho alkynylation of aromatic N methoxyamides with hypervalent iodine-alkyne reagent using a ruthenium catalyst is described. The reaction proceeds under mild reaction conditions with broad substrate scope. A possible catalytic cycle involving a ruthenium carboxylate assisted C-H bond cleavage is proposed from the preliminary mechanistic evidence. PMID- 27357725 TI - Monetary value of self-reported diets and associations with sociodemographic characteristics and dietary intake among Japanese adults: analysis of nationally representative surveys. AB - OBJECTIVE: To examine the relationships of monetary value of diets with sociodemographic and lifestyle characteristics and dietary intake among Japanese adults. DESIGN: Cross-sectional study based on two nationally representative surveys: the Comprehensive Survey of Living Conditions and the National Health and Nutrition Survey, 2013. Dietary intake was assessed by a 1 d semi-weighed household dietary record with information on individual proportion of intakes. Diet cost was estimated by linking dietary data with retail food prices. A wide variety of sociodemographic and lifestyle variables were obtained from the two surveys. SETTING: A random sample of nationally representative households in Japan. SUBJECTS: Japanese adults aged 20 years or older (n 4658). RESULTS: Lower energy-adjusted diet cost (Japanese yen/4184 kJ) was significantly associated with being younger, having a lower education, less equivalent monthly household expenditure, large household size, less physical activity and living in rented houses. Lower diet cost was associated with a lower intake of pulses, vegetables, fruits, fish, meat and dairy products, and a higher intake of grain, eggs, and fats and oils. At the nutrient level, lower diet cost was associated with a lower intake of protein, alcohol, dietary fibre, cholesterol and all vitamins and minerals examined, and a higher intake of carbohydrate. Diet cost was inversely associated with dietary energy density. CONCLUSION: These data suggest that certain low socio-economic subgroups in Japan consume diets of lower monetary value, resulting in a lower quality of food and nutrient intake pattern except for lower sodium, cholesterol and alcohol consumption. PMID- 27357727 TI - Neuroticism and maladaptive coping in patients with functional somatic syndromes. AB - OBJECTIVES: The cognitive-behavioural model of functional somatic syndromes (FSS) proposes a multifactorial aetiology consisting of predisposing, precipitating and perpetuating factors. In this study, we sought to investigate three questions that can be drawn from this model: (1) Do patients with FSS show high levels of neuroticism? (2) Does neuroticism affect physical health and social functioning, either directly or indirectly through maladaptive coping? (3) Does more adaptive coping mediate the effect of cognitive-behavioural therapy (CBT) on outcome? DESIGN: Secondary analysis of a randomized controlled trial (RCT) using additional data. METHOD: We used yet unpublished data on neuroticism (measured with Temperament and Character Inventory, Revised) and coping (measured with Coping Strategies Questionnaire) together with already reported outcomes (physical health and social functioning measured with SF-36) from an RCT comparing group CBT with enhanced usual care in 120 patients with a range of FSS. Neuroticism was measured at referral, while coping and outcomes were measured at referral, baseline, 4 and 16 months after randomization. Our hypotheses were explored through a series of cross-sectional (linear regression and structural equation models) and longitudinal (mediation) analyses. RESULTS: Patients with FSS showed higher levels of neuroticism than two healthy comparison groups. At referral, symptom catastrophizing partly mediated the negative association between neuroticism and outcome. Reduction in symptom catastrophizing during group CBT partially mediated its long-term effect. CONCLUSIONS: The results give support to a generic cognitive-behavioural model of FSS. Targeting symptom catastrophizing may be an essential component in CBT for patients with FSS, regardless of their specific diagnosis. Statement of contribution What is already known on this subject? Previous studies have found support for single components of the cognitive-behavioural model such as dysfunctional illness beliefs or avoidant coping. Most studies have investigated single functional somatic syndromes (FSS) such as fibromyalgia or irritable bowel syndrome. What does this study add? Predisposing neuroticism was linked to poor physical health through symptom catastrophizing across a range of FSS. Reduced symptom catastrophizing during group cognitive-behavioural therapy partially mediated its long-term effect. Addressing symptom catastrophizing may be a key element of the management of patients with FSS. PMID- 27357729 TI - Tanshinone IIA attenuates experimental autoimmune encephalomyelitis in rats. AB - Multiple sclerosis (MS) is an inflammatory autoimmune neurodegenerative disease, which features focal demyelination and inflammatory cell infiltration of the brain and the spinal cord. Tanshinone IIA (TSIIA), one of the major fat-soluble components of Salvia miltiorrhiza (Danshen), has anti-inflammatory, immunoregulatory and neuroprotective activity; however, its efficacy in MS remains unknown. The current study was designed to investigate the potential therapeutic function of TSIIA on MS in the experimental autoimmune encephalomyelitis (EAE) rat model. In comparison to the vehicle control group, the TSIIA-treated groups showed notably improved clinical symptoms and pathological changes, including central nervous system inflammatory cell infiltration and demyelination. Following administration of TSIIA, the quantity of CD4+ T cells, CD8+ T cells and macrophages/microglia in the spinal cord were reduced to different extents. Furthermore, TSIIA was also shown to downregulate interleukin (IL)-17 and IL-23 levels in the brain and serum of EAE rats. The results collectively provide evidence that TSIIA alleviates EAE and support its utility as a novel therapy for MS. PMID- 27357728 TI - A model to predict the risk of lethal nasopharyngeal necrosis after re irradiation with intensity-modulated radiotherapy in nasopharyngeal carcinoma patients. AB - BACKGROUND: For patients with nasopharyngeal carcinoma (NPC) who undergo re irradiation with intensity-modulated radiotherapy (IMRT), lethal nasopharyngeal necrosis (LNN) is a severe late adverse event. The purpose of this study was to identify risk factors for LNN and develop a model to predict LNN after radical re irradiation with IMRT in patients with recurrent NPC. METHODS: Patients who underwent radical re-irradiation with IMRT for locally recurrent NPC between March 2001 and December 2011 and who had no evidence of distant metastasis were included in this study. Clinical characteristics, including recurrent carcinoma conditions and dosimetric features, were evaluated as candidate risk factors for LNN. Logistic regression analysis was used to identify independent risk factors and construct the predictive scoring model. RESULTS: Among 228 patients enrolled in this study, 204 were at risk of developing LNN based on risk analysis. Of the 204 patients treated, 31 (15.2%) developed LNN. Logistic regression analysis showed that female sex (P = 0.008), necrosis before re-irradiation (P = 0.008), accumulated total prescription dose to the gross tumor volume (GTV) >=145.5 Gy (P = 0.043), and recurrent tumor volume >=25.38 cm(3) (P = 0.009) were independent risk factors for LNN. A model to predict LNN was then constructed that included these four independent risk factors. CONCLUSIONS: A model that includes sex, necrosis before re-irradiation, accumulated total prescription dose to GTV, and recurrent tumor volume can effectively predict the risk of developing LNN in NPC patients who undergo radical re-irradiation with IMRT. PMID- 27357730 TI - Pyruvate dehydrogenase alpha 1 as a target of omega-3 polyunsaturated fatty acids in human prostate cancer through a global phosphoproteomic analysis. AB - Prostate cancer is one of the leading cancers in men. Taking dietary supplements, such as fish oil (FO), which is rich in n-3 polyunsaturated fatty acids (PUFAs), has been employed as a strategy to lower prostate cancer risk and control disease progression. In this study, we investigated the global phosphoproteomic changes induced by FO using a combination of phosphoprotein-enrichment strategy and high resolution tandem mass spectrometry. We found that FO induces many more phosphorylation changes than oleic acid when they both are compared to control group. Quantitative comparison between untreated group and FO- or oleic acid treated groups uncovered a number of important protein phosphorylation changes induced by n-3PUFAs. This phosphoproteomic discovery study and the follow-up Western Blot validation study elucidate that phosphorylation levels of the two regulatory serine residues in pyruvate dehydrogenase alpha 1 (PDHA1), serine-232 and serine-300, are significantly decreased upon FO treatment. As expected, increased pyruvate dehydrogenase activity was also observed. This study suggests that FO-induced phosphorylation changes in PDHA1 is more likely related to the glucose metabolism pathway, and n-3 PUFAs may have a role in controlling the balance between lipid and glucose oxidation. PMID- 27357731 TI - Catalytic Hydrodeoxygenation of Bio-oil Model Compounds over Pt/HY Catalyst. AB - The hydrodeoxygenation of a model compound of lignin-derived bio-oil, guaiacol, which can be obtained from the pyrolysis of biomass to bio-oil, has attracted considerable research attention because of its huge potential as a substitute for conventional fuels. In this study, platinum-loaded HY zeolites (Pt/HY) with different Si/Al molar ratios were used as catalysts for the hydrodeoxygenation of guaiacol, anisole, veratrole, and phenol to a range of hydrocarbons, such as cyclohexane. The cyclohexane (major product) yield increased with increasing number of acid sites. To produce bio-oil with the maximum level of cyclohexane and alkylated cyclohexanes, which would be suitable as a substitute for conventional transportation fuels, the Si/Al molar ratio should be optimized to balance the Pt particle-induced hydrogenation with acid site-induced methyl group transfer. The fuel properties of real bio-oil derived from the fast pyrolysis of cork oak was improved using the Pt/HY catalyst. PMID- 27357732 TI - Corrosion Behavior of Ti60 Alloy under a Solid NaCl Deposit in Wet Oxygen Flow at 600 degrees C. AB - The corrosion behavior of Ti60 alloy covered with a solid NaCl deposit in wet oxygen flow at 600 degrees C has been studied further by SEM, EDX, XPS, XRD, TEM and EPMA analysis. The results show that solid NaCl and H2O react with Ti oxides, which destroyed the Ti oxide scale to yield the non-protective Na4Ti5O12 and other volatile species. The resulting corrosion product scale was multilayered and contained abundant rapid diffusion channels leading to the fast diffusion which improved the corrosion rate. A possible mechanism has been proposed for the NaCl-covered Ti60 alloy, based on the experimental results. PMID- 27357733 TI - A case of hyaluronic acid injections triggering cutaneous sarcoidosis at previously treated sites. PMID- 27357734 TI - Effects of AP-1 and NF-kappaB inhibitors on colonic endocrine cells in rats with TNBS-induced colitis. AB - Interactions between intestinal neuroendocrine peptides/amines and the immune system appear to have an important role in the pathophysiology of inflammatory bowel disease (IBD). The present study investigated the effects of activator protein (AP)-1 and nuclear factor (NF)-kappaB inhibitors on inflammation-induced alterations in enteroendocrine cells. A total of 48 male Wistar rats were divided into the following four groups (n=12 rats/group): Control, trinitrobenzene sulfonic acid (TNBS)-induced colitis only (TNBS group), TNBS-induced colitis with 3-[(dodecylthiocarbonyl)-methyl]-glutarimide (DTCM-G) treatment (DTCM-G group), and TNBS-induced colitis with dehydroxymethylepoxyquinomicin (DHMEQ) treatment (DHMEQ group). A total of 3 days following administration of TNBS, the rats were treated as follows: The control and TNBS groups received 0.5 ml vehicle (0.5% carboxymethyl cellulose; CMC), respectively; the DTCM-G group received DTCM-G (20 mg/kg body weight) in 0.5% CMC; and the DHMEQ group received DHMEQ (15 mg/kg body weight) in 0.5% CMC. All injections were performed intraperitoneally twice daily for 5 days. The rats were sacrificed, and tissue samples obtained from the colon were examined histopathologically and immunohistochemically. Inflammation was evaluated using a scoring system. In addition, the sections were immunostained for chromogranin A (CgA), serotonin, peptide YY (PYY), oxyntomodulin, pancreatic polypeptide (PP) and somatostatin, and immunostaining was quantified using image analysis software. The density of cells expressing CgA, PYY and PP was significantly lower in the TNBS group compared with in the control group, whereas the density of cells expressing serotonin, oxyntomodulin and somatostatin was significantly higher in the TNBS group compared with in the control group. None of the endocrine cell types differed significantly between the control group and either the DTCM-G or DHMEQ groups. All of the colonic endocrine cell types were affected in rats with TNBS-induced colitis. The expression density of these endocrine cell types was restored to control levels following treatment with AP-1 or NF-kappaB inhibitors. These results indicated that the immune system and enteroendocrine cells interact in IBD. PMID- 27357736 TI - Flexible and Porous Nanocellulose Aerogels with High Loadings of Metal-Organic Framework Particles for Separations Applications. AB - Flexible and porous aerogels are obtained by combining functional metal-organic frameworks (MOFs) and structural cellulose nanocrystals via a straightforward water-based sol-gel process, followed by freeze-drying. The aerogels have a hierarchical porous structure with controllable MOF loading up to 50 wt%. These hybrid materials can be used as absorbents for water purification. PMID- 27357735 TI - Circadian variation of metabotropic glutamate receptor 5 availability in the rat brain. AB - The metabotrophic subtype 5 glutamate receptor (mGluR5) plays a critical role in synaptic plasticity besides its involvement in numerous neurological disorders, such as depression. As mGluR5 availability in humans is altered in sleep deprivation, we hypothesized that mGluR5 availability underlies a circadian variation. To investigate whether mGluR5 underlies potential circadian changes we measured its density in a randomized fashion at six different daytimes in 11 adult Sprague-Dawley rats. mGluR5 density was quantified by positron emission tomography (PET) using the radioactive ligand [11 C]ABP688. [11 C]ABP688 uptake was quantified in nine regions of interest with a reference tissue model. Significant differences in the binding potential (BPND ) and therefore mGluR5 availability between the different circadian times were found in cortex, cingulate cortex, amygdala, caudate putamen and nucleus accumbens. Further post hoc statistical analysis (Tukey-Kramer test) of the different time-points revealed significant changes in BPND between 07:00 hours (start of light-on phase) and 15:00 hours (last time-point of the light-on phase) in the caudate putamen. This study shows that mGluR5 availability is increased during the light on, or sleep phase, of rodents by approximately 10%. Given that altered mGluR5 densities play a role in psychiatric disorders, further investigation is warranted to evaluate their circadian involvement in mood changes in humans. PMID- 27357737 TI - Retreatment efficacy and predictors of ledipasvir plus sofosbuvir to HCV genotype 1 in Japan. AB - Predictors of treatment efficacy with ledipasvir plus sofosbuvir as direct-acting antiviral (DAA) regimen for HCV infection are still unclear. Retreatment efficacy of ledipasvir plus sofosbuvir for failures to prior DAA regimens, including NS5A inhibitors, are also unknown because resistance-associated variants (RAVs) in NS5A have been shown to persist up to the long-term of post-treatment. One hundred seventy-five patients with chronic HCV genotype 1 infection, without decompensated liver cirrhosis and hepatocellular carcinoma, were evaluated SVR12 by ledipasvir 90 mg plus sofosbuvir 400 mg once-daily for 12 weeks. Overall, SVR12 were 92%, based on intention to treat analysis. In failures to daclatasvir plus asunaprevir, SVR12 were 71%. The study using ultra-deep sequencing showed that ledipasvir plus sofosbuvir was effective to one case of failures to daclatasvir plus asunaprevir with multidrug RAVs (triple mutation in NS3 D168/NS5A-L31/NS5A-Y93). Multivariate analysis identified FIB4 index (<3.25), IL28B rs8099917 (TT type), and NS5A-L31 (Wild type) as significant determinants of SVR12. SVR12 rates in patients with three factors of poor response (RAVs Positive, IL28B non-TT, and FIB4 index >=3.25) simultaneously were significantly lower than those of the other patients. Prediction of response to therapy based on combination of three predictors had high sensitivity and positive predictive values. In conclusions, this study indicated the favorable efficacy of ledipasvir plus sofosbuvir for HCV genotype 1 infection, including multidrug RAVs in Japan. Treatment efficacy could be predicted by the combination of viral and host factors. J. Med. Virol. 89:284-290, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27357738 TI - Safety, tolerability and clinical pharmacology of dabigatran etexilate in adolescents. An open-label phase IIa study. AB - Venous thromboembolism (VTE) incidence is increasing among children owing to many factors, including improved diagnosis of VTE. There is a need for alternative treatment options. Our objective was to investigate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of dabigatran etexilate in adolescents with VTE. Adolescents aged 12 to <18 years (n = 9) who successfully completed planned treatment for primary VTE were administered dabigatran etexilate twice daily for three days; initially 1.71 (+/- 10 %) mg/kg (80 % of a 150 mg/70 kg twice daily adult dose), followed by 2.14 (+/- 10 %) mg/kg (target adult dose adjusted for patient's weight), if there were no safety concerns. No bleeding events, deaths or drug-related serious adverse events (AEs) were reported; three treatment emergent AEs, all gastrointestinal-related, occurred in two patients. In these adolescent patients with normal renal function, presumed steady-state trough plasma concentrations of dabigatran were low (geometric mean dose-normalised total dabigatran plasma concentration: 0.493 ng/ml/mg at 72 hours). Total dabigatran concentrations were well predicted by the RE-LY(r) population PK model (94 % of trough concentrations were within the 80 % prediction interval). The relationship between total dabigatran plasma concentration, diluted thrombin time and ecarin clotting time (ECT) was linear; the relationship with activated partial thromboplastin time (aPTT) was non-linear. Adult population PK/PD models predicted the adolescent concentration-ECT and -aPTT relationships well. In conclusion, dabigatran etexilate was generally well tolerated, except for occurrence of dyspepsia in two patients, over the three-day treatment period. The dabigatran PK/PD relationship observed in adolescent patients was similar to that in adult patients. PMID- 27357739 TI - Is skin penetration a determining factor in skin sensitization potential and potency? Refuting the notion of a LogKow threshold for skin sensitization. AB - It is widely accepted that substances that cannot penetrate through the skin will not be sensitizers. LogKow and molecular weight (MW) have been used to set thresholds for sensitization potential. Highly hydrophilic substances e.g. LogKow <= 1 are expected not to penetrate effectively to induce sensitization. To investigate whether LogKow >1 is a true requirement for sensitization, a large dataset of substances that had been evaluated for their skin sensitization potential under Registration, Evaluation, Authorisation and restriction of CHemicals (REACH), together with available measured LogKow values was compiled using the OECD eChemPortal. The incidence of sensitizers relative to non sensitizers above and below a LogKow of 1 was explored. Reaction chemistry principles were used to explain the sensitization observed for the subset of substances with a LogKow <=0. 1482 substances were identified with skin sensitization data and measured LogKow values. 525 substances had a measured LogKow <= 1, 100 of those were sensitizers. There was no significant difference in the incidence of sensitizers above and below a LogKow of 1. Reaction chemistry principles that had been established for lower MW and more hydrophobic substances were found to be still valid in rationalizing the skin sensitizers with a LogKow <= 0. The LogKow threshold arises from the widespread misconception that the ability to efficiently penetrate the stratum corneum is a key determinant of sensitization potential and potency. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27357740 TI - A fundamental study of the impact of pressure on the adsorption mechanism in reversed-phase liquid chromatography. AB - A fundamental investigation of the pressure effect on individual adsorption sites was undertaken based on adsorption energy distribution and adsorption isotherm measurements. For this purpose, we measured adsorption equilibrium data at pressures ranging from 100 to 1000bar at constant flow and over a wide concentration range for three low-molecular-weight solutes, antipyrine, sodium 2 naphthalenesulfonate, and benzyltriethylammonium chloride, on an Eternity C18 stationary phase. The adsorption energy distribution was bimodal for all solutes, remaining clearly so at all pressures. The bi-Langmuir model best described the adsorption in these systems and two types of adsorption sites were identified, one with a low and another with a high energy of interaction. Evidence exists that the low-energy interactions occur at the interface between the mobile and stationary phases and that the high-energy interactions occur nearer the silica surface, deeper in the C18 layer. The contribution of each type of adsorption site to the retention factor was calculated and the change in solute molar volume from the mobile to stationary phase during the adsorption process was estimated for each type of site. The change in solute molar volume was 2-4 times larger at the high-energy site, likely because of the greater loss of solute solvation layer when penetrating deeper into the C18 layer. The association equilibrium constant increased with increasing pressure while the saturation capacity of the low-energy site remained almost unchanged. The observed increase in saturation capacity for the high-energy site did not affect the column loading capacity, which was almost identical at 50- and 950-bar pressure drops over the column. PMID- 27357741 TI - Microfluidics-based side view flow chamber reveals tether-to-sling transition in rolling neutrophils. AB - Neutrophils rolling at high shear stress (above 6 dyn/cm(2)) form tethers in the rear and slings in the front. Here, we developed a novel photo-lithographically fabricated, silicone(PDMS)-based side-view flow chamber to dynamically visualize tether and sling formation. Fluorescently membrane-labeled mouse neutrophils rolled on P-selectin substrate at 10 dyn/cm(2). Most rolling cells formed 5 tethers that were 2-30 MUm long. Breaking of a single tether caused a reproducible forward microjump of the cell, showing that the tether was load bearing. About 15% of all tether-breaking events resulted in slings. The tether to-sling transition was fast (<100 ms) with no visible material extending above the rolling cell, suggesting a very low bending modulus of the tether. The sling downstream of the rolling cell aligned according to the streamlines before landing on the flow chamber. These new observations explain how slings form from tethers and provide insight into their biomechanical properties. PMID- 27357742 TI - Secondary metabolites of Xylaria sp., an endophytic fungus from Taxus mairei. AB - One new metabolite 3,7-dimethyl-9-(-2,2,5,5-tetramethyl-1,3-dioxolan-4-yl)nona 1,6-dien-3-ol, together with nine known compounds, were isolated from the strain Xylaria sp., an endophytic fungus of Taxus mairei. Their structures were deduced from 1D and 2D NMR data. In vitro cytotoxicity and antibacterial activity of these compounds were evaluated. Some of them exhibited substantial activity. PMID- 27357743 TI - Endogenous Cu in the central nervous system fails to satiate the elevated requirement for Cu in a mutant SOD1 mouse model of ALS. AB - Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease, a fatal degenerative disorder in which motor neurons in the central nervous system (CNS) progressively deteriorate. Most cases of ALS are sporadic, but 10% are familial and mutations affecting the copper (Cu)-dependent antioxidant Cu/Zn-superoxide dismutase (SOD1) are the most common familial cause. Cu malfunction is evident in CNS tissue from transgenic mice that over-express mutant SOD1 and modulating Cu bioavailability in the CNS provides positive therapeutic outcomes. In the present study we assessed levels of Cu and Zn, SOD activity, and SOD1 protein levels in CNS and non-CNS tissue from transgenic mutant SOD1 mice (SOD1(G37R)) and non-transgenic controls. Physiological SOD1 binds one structural Zn and one catalytic Cu per subunit. Due to over-expression of the transgene, SOD activity and SOD1 protein levels are elevated in all tissues examined from the SOD1(G37R) mice and a commensurate increase in Zn is evident. There is a comparable increase in Cu in non-CNS tissue, but the increase in Cu in the SOD1(G37R) mouse brain is limited and there is no increase in Cu in the spinal cord. The limited change in CNS Cu is associated with a strong disparity between SOD1 protein and SOD activity in the brain and spinal cord. We hypothesise that the limited capacity for CNS tissue to respond to an increased requirement for bioavailable Cu contributes to CNS vulnerability in ALS. PMID- 27357744 TI - Validation of a rapid neurodevelopmental assessment tool for 10- to 16-year-old young adolescents in Bangladesh. AB - OBJECTIVE: To validate a Rapid Neurodevelopmental Assessment (RNDA) tool for use by child health professionals to determine neurodevelopmental impairments (NDIs) in young adolescents aged 10-16 years in Bangladesh. STUDY DESIGN: In a convenience sample of community children (n = 47), inter-rater reliability was determined between four testers, and concurrent validity was determined by simultaneous administration of an intelligence quotient (IQ) test (Wechsler Intelligence Scale for Children, Revised) by a child psychologist. RESULTS: Inter rater reliability was excellent between the testers on the 47 children administered the RNDA (kappa = 1.00). Significantly lower IQ scores were obtained in those identified with 'any (>1) NDI' (n = 34) compared with those with no NDI (n = 13) on Verbal IQ (P-value < 0.0001), Performance IQ (P-value < 0.0001) and Full-scale IQ (P-value < 0.0001) scores on the Wechsler Intelligence Scale for Children, Revised. CONCLUSION: The RNDA shows promise as a tool for use by child health professionals for identifying NDIs in young adolescents aged 10-16 years. A larger study sample is needed to determine its usefulness for identification of some impairments not found in the study population, i.e. gross motor, fine motor, hearing and seizures. PMID- 27357745 TI - Nursing Problems in Care of a Patient with Very Early HCV Infection Recurrence After Liver Transplantation: A Case Report. AB - BACKGROUND Recurrent HCV infection following liver transplantation is a common problem, and usually has a more aggressive course than primary infection. The aim of the paper was to present nursing problems in the care of a 22-year-old female patient after liver transplantation (Ltx) with a rapid recurrence of HCV infection shortly after Ltx. CASE REPORT Ltx was performed 22 July 2012 due to chronic cirrhosis secondary to HCV infection with viremia (HCV PCR 3.5*107 IU/mL). Graft function worsened 14 days following transplantation. Acute cholestatic hepatitis related to HCV reinfection was diagnosed based on biopsy. During a period of 20 months the patient received 3 different antiviral treatment regimens, beginning with a dual therapy (Interferon and Ribavirin), followed by the inclusion of Telaprevir, then Daclatasvir; however, these treatments were not successful. The fourth-line regimen with sofosbuvir (EU medical experiment) led to viremia elimination (HCV PCR) after 5 weeks of treatment. However, hepatic failure stabilization was unsuccessful, there was an increase in encephalopathy, and the MELD score was 25. Therefore, the patient underwent liver retransplantation. In the post-transplantation period, the patient was in good condition, with no viremia. CONCLUSIONS The most common nursing problems in the care of the patient were associated with the diagnostic process, therapies used (including experimental treatment), and progressive liver failure. The therapeutic success should be attributed to the intensive supervision and monitoring of viremia, immediate inclusion of adequate treatment methods, adequate patient preparation for diagnostic tests, and careful care after diagnostics, as well as psychological support and education. PMID- 27357746 TI - Self-Reported Napping Behavior Change After Continuous Positive Airway Pressure Treatment in Older Adults with Obstructive Sleep Apnea. AB - OBJECTIVES: To assess the effect of continuous positive airway pressure (CPAP) on napping behavior in adults aged 60 and older with obstructive sleep apnea hypopnea syndrome (OSAHS). DESIGN: Retrospective cohort study using questionnaires. SETTING: Sleep center. PARTICIPANTS: Individuals starting CPAP treatment between April 2010 and March 2012 (mean age 65.2 +/- 4.7; M:F = 3.9:1; N = 107). MEASUREMENTS: All subjects underwent sleep studies, clinical reviews, and CPAP adherence checks and completed a questionnaire regarding CPAP adherence, current employment status, sleep patterns before and after CPAP, and factors affecting their current sleep patterns. RESULTS: CPAP treatment duration was 82.7 +/- 30.0 weeks, and objective adherence was 5.4 +/- 2.0 hours per night overall. Daytime nap frequency before CPAP treatment was higher in those with a history of stroke or cardiovascular disease. Both sexes had a significant reduction in daytime napping (men, P < .001; women, P = .008), evening napping (men, P < .001; women, P = .02), and daily nap duration (men, P < .001; women, P = .02). Logistic regression analysis showed that the reduction in self-reported daily nap duration was associated with younger age (odds ratio (OR) = 0.86, P = .04), a decrease in ESS score (OR = 1.20, P = .03), and longer self-reported daily nap duration at baseline (OR = 31.52, P < .001). CONCLUSION: Long-term CPAP treatment in older adults with OSAHS can play a significant role in reducing nap frequency and daily nap duration. Aging or shorter baseline daily nap duration may attenuate this effect. PMID- 27357748 TI - Large-scale synthesis of ultrathin tungsten oxide nanowire networks: an efficient catalyst for aerobic oxidation of toluene to benzaldehyde under visible light. AB - As a very important chemical raw material, the selective formation of benzaldehyde from toluene at preparative or industrial levels requires the use of highly corrosive chlorine and high reaction temperatures, which severely corrodes equipment, pollutes the environment, and consumes a lot of energy. Herein, we report a robust and highly active catalyst for the benzaldehyde evolution reaction that is constructed by the surfactant-free growth of oxygen vacancy-rich W18O49 ultrathin nanowire networks. Under atmospheric pressure and visible-light irradiation, the new catalyst can selectively (92% selectivity) catalyze the aerobic oxidation of toluene to benzaldehyde with yields of above 95%. PMID- 27357747 TI - Digital Quantification of DNA Replication and Chromosome Segregation Enables Determination of Antimicrobial Susceptibility after only 15 Minutes of Antibiotic Exposure. AB - Rapid antimicrobial susceptibility testing (AST) would decrease misuse and overuse of antibiotics. The "holy grail" of AST is a phenotype-based test that can be performed within a doctor visit. Such a test requires the ability to determine a pathogen's susceptibility after only a short antibiotic exposure. Herein, digital PCR (dPCR) was employed to test whether measuring DNA replication of the target pathogen through digital single-molecule counting would shorten the required time of antibiotic exposure. Partitioning bacterial chromosomal DNA into many small volumes during dPCR enabled AST results after short exposure times by 1) precise quantification and 2) a measurement of how antibiotics affect the states of macromolecular assembly of bacterial chromosomes. This digital AST (dAST) determined susceptibility of clinical isolates from urinary tract infections (UTIs) after 15 min of exposure for all four antibiotic classes relevant to UTIs. This work lays the foundation to develop a rapid, point-of-care AST and strengthen global antibiotic stewardship. PMID- 27357750 TI - Proteomic analysis of differentially expressed proteins in the three developmental stages of Trichinella spiralis. AB - Trichinella spiralis, an intracellular parasitic nematode, can cause severe foodborne zoonosis, trichinellosis. The life cycle of T. spiralis consists of adult (Ad), muscle larvae (ML) and newborn larvae (NBL). The protein profiles in different developmental stages of the parasite remain unknown. In the present study, proteins from lysates of Ad, ML and NBL were identified by isobaric tags for relative and absolute quantitation (iTRAQ). A total of 4691 proteins were identified in all the developmental stages, of which 1067 proteins were differentially expressed. The number of up-regulated proteins in NBL was higher than that of the other two groups. The protein profiles from Ad, ML and NBL were compared in pairs. The identified proteins were involved in various functions of T. spiralis life cycle, including sexual maturity, metabolism, utilization of carbohydrates, lipids and nucleotides, and other crucial developmental processes that occur at distinct stages. Further investigation of the transcriptional levels of major sperm protein, serine protease, zinc finger protein, etc. from the different protein profiles using quantitative RT-PCR showed identical results to the iTRAQ analysis. The differentially expressed proteins that are involved in developmental regulation and host-parasite interactions should be further studied. PMID- 27357751 TI - Recent Developments in the Chiral Bronsted Acid-catalyzed Allylboration Reaction with Polyfunctionalized Substrates. AB - Asymmetric allylboration has played a central role in organic synthesis ever since the pioneering work by Hoffman and Brown, having found applications in the total synthesis of many natural products. A new dawn for this 40 year-old reaction occurred with the beginning of the new century when the first catalytic asymmetric methods came into play. In less than one decade, several methodologies, able to achieve the desired homoallylic alcohols with ee ranges in the high 90s, were developed. Among them, in the present account, we will disclose our contribution to the development of the chiral binolphosphoric derived Bronsted acid-catalyzed allylboration of aldehydes originally reported by Antilla in 2010. Our contribution to this field lies in its application to polyfunctionalized systems, both on the aldehyde and the allylboronate in question, which enables the rapid construction of molecular diversity and complexity. Parts of the work described herein have been carried out in collaboration with the groups of Profs. Akiyama and Houk. PMID- 27357749 TI - An ABA-increased interaction of the PYL6 ABA receptor with MYC2 Transcription Factor: A putative link of ABA and JA signaling. AB - Abscisic acid (ABA) is a plant hormone that mediates abiotic stress tolerance and regulates growth and development. ABA binds to members of the PYL/RCAR ABA receptor family that initiate signal transduction inhibiting type 2C protein phosphatases. Although crosstalk between ABA and the hormone Jasmonic Acid (JA) has been shown, the molecular entities that mediate this interaction have yet to be fully elucidated. We report a link between ABA and JA signaling through a direct interaction of the ABA receptor PYL6 (RCAR9) with the basic helix-loop helix transcription factor MYC2. PYL6 and MYC2 interact in yeast two hybrid assays and the interaction is enhanced in the presence of ABA. PYL6 and MYC2 interact in planta based on bimolecular fluorescence complementation and co immunoprecipitation of the proteins. Furthermore, PYL6 was able to modify transcription driven by MYC2 using JAZ6 and JAZ8 DNA promoter elements in yeast one hybrid assays. Finally, pyl6 T-DNA mutant plants show an increased sensitivity to the addition of JA along with ABA in cotyledon expansion experiments. Overall, the present study identifies a direct mechanism for transcriptional modulation mediated by an ABA receptor different from the core ABA signaling pathway, and a putative mechanistic link connecting ABA and JA signaling pathways. PMID- 27357752 TI - Australian and New Zealand Society for Geriatric Medicine Position Statement Abstract: Undernutrition and the older person. PMID- 27357754 TI - Sex-related Differences in Emergency Department Renal Colic Management: Females Have Fewer Computed Tomography Scans but Similar Outcomes. AB - BACKGROUND: Sex-related differences occur in many areas of medicine. Emergency department (ED) studies have suggested differences in access to care, diagnostic imaging use, pain management, and intervention. We investigated sex-based differences in the care and outcomes for ED patients with acute renal colic. METHODS: This was a multicenter population-based retrospective observational cohort study using administrative data and supplemented by structured chart review. All patients seen in Calgary Health Region EDs between January 1 and December 31, 2014, with an ED diagnosis of renal colic based on the following ICD 10 codes were eligible for inclusion: calculus of kidney (N200), calculus of ureter (N201), calculus of kidney with calculus of ureter (N202), hydronephrosis with renal and ureteral calculous obstruction (N132), unspecified renal colic (N23), and unspecified urinary calculus (N209). ED visit data and test results were accessed in the regional ED clinical database. Stone characteristics were captured from diagnostic imaging reports. Regional hospital databases were used to identify subsequent ED encounters, hospital admissions, and surgical procedures within 60 days. Outcomes were stratified by sex. The primary outcome, intended as a marker of overall effectiveness of ED care, was the unscheduled 7 day ED revisit rate among patients who were discharged home after their index ED visit. Secondary outcomes included ED pain management as reflected by administration of narcotics or intravenous nonsteroidals, the performance of advanced imaging-either ultrasound (US) or computed tomography (CT), and the proportion of patients who required hospitalization or surgical intervention within 60 days. RESULTS: From January 1 to December 31, 2014, a total of 3,104 eligible patients were studied: 1,111 women (35.8%) and 1,993 men (64.2%). Baseline characteristics, access times, analgesic use, and admission rates were similar in both groups. Men were more likely to have CT (68.9% vs. 58.5%, difference = 10.4%, 95% confidence interval [CI] = 6.8 to 14.0) while women were more likely to have US (20.8% vs. 9.6%, difference = 11.2%, 95% CI = 8.4 to 13.9). At 7 days, 17.9% of women and 19.0% of men who were discharged after their index ED visit required an ED revisit (difference = 1.1%, 95% CI = -2.8 to 4.9). Men were more likely to be hospitalized at 7 days (9.8% vs. 6.5%, difference = 3.3%, 95% CI = 0.6 to 6.0). CONCLUSION: This study shows greater reliance on US in females but no other sex-specific differences in the management of ED patients with acute renal colic. Higher CT use in men was not associated with improved outcomes, and we found no important differences in access to care, diagnostic or treatment intensity, or revisit rates as a marker of care effectiveness. PMID- 27357756 TI - Meet the challenge of interdisciplinary science. PMID- 27357757 TI - Brexit vote highlights lack of leaving plan. PMID- 27357755 TI - Switching stiction and adhesion of a liquid on a solid. AB - When a gecko moves on a ceiling it makes use of adhesion and stiction. Stiction- static friction--is experienced on microscopic and macroscopic scales and is related to adhesion and sliding friction. Although important for most locomotive processes, the concepts of adhesion, stiction and sliding friction are often only empirically correlated. A more detailed understanding of these concepts will, for example, help to improve the design of increasingly smaller devices such as micro and nanoelectromechanical switches. Here we show how stiction and adhesion are related for a liquid drop on a hexagonal boron nitride monolayer on rhodium, by measuring dynamic contact angles in two distinct states of the solid-liquid interface: a corrugated state in the absence of hydrogen intercalation and an intercalation-induced flat state. Stiction and adhesion can be reversibly switched by applying different electrochemical potentials to the sample, causing atomic hydrogen to be intercalated or not. We ascribe the change in adhesion to a change in lateral electric field of in-plane two-nanometre dipole rings, because it cannot be explained by the change in surface roughness known from the Wenzel model. Although the change in adhesion can be calculated for the system we study, it is not yet possible to determine the stiction at such a solid-liquid interface using ab initio methods. The inorganic hybrid of hexagonal boron nitride and rhodium is very stable and represents a new class of switchable surfaces with the potential for application in the study of adhesion, friction and lubrication. PMID- 27357758 TI - Gene-therapy trials must proceed with caution. PMID- 27357759 TI - Stop teaching Indians to copy and paste. PMID- 27357772 TI - NASA's Juno spacecraft prepares to probe Jupiter's mysteries. PMID- 27357771 TI - UK scientists in limbo after Brexit shock. PMID- 27357773 TI - Stressed Indus River threatens Pakistan's water supplies. PMID- 27357774 TI - ArXiv preprint server plans multimillion-dollar overhaul. PMID- 27357775 TI - Correction. PMID- 27357776 TI - Dolly at 20: The inside story on the world's most famous sheep. PMID- 27357777 TI - Why ultra-powerful radio bursts are the most perplexing mystery in astronomy. PMID- 27357778 TI - Make climate-change assessments more relevant. PMID- 27357779 TI - Policy: Social-progress panel seeks public comment. PMID- 27357783 TI - Alien species: Pre-emptive action against EU invasives. PMID- 27357784 TI - Gender balance: Supporting women postdocs in Israel. PMID- 27357785 TI - Junior researchers: Fewer papers would scotch early careers. PMID- 27357786 TI - Life on Earth: Count cryptic species in biodiversity tally. PMID- 27357788 TI - Thomas Kibble (1932-2016). PMID- 27357787 TI - Carbon tracking: Limit uncertainties in land emissions. PMID- 27357789 TI - Physiology: Stressed-out chromatin promotes longevity. PMID- 27357790 TI - Earth science: An extended yardstick for climate variability. PMID- 27357792 TI - Paris Agreement climate proposals need a boost to keep warming well below 2 degrees C. AB - The Paris climate agreement aims at holding global warming to well below 2 degrees Celsius and to "pursue efforts" to limit it to 1.5 degrees Celsius. To accomplish this, countries have submitted Intended Nationally Determined Contributions (INDCs) outlining their post-2020 climate action. Here we assess the effect of current INDCs on reducing aggregate greenhouse gas emissions, its implications for achieving the temperature objective of the Paris climate agreement, and potential options for overachievement. The INDCs collectively lower greenhouse gas emissions compared to where current policies stand, but still imply a median warming of 2.6-3.1 degrees Celsius by 2100. More can be achieved, because the agreement stipulates that targets for reducing greenhouse gas emissions are strengthened over time, both in ambition and scope. Substantial enhancement or over-delivery on current INDCs by additional national, sub national and non-state actions is required to maintain a reasonable chance of meeting the target of keeping warming well below 2 degrees Celsius. PMID- 27357793 TI - The Asian monsoon over the past 640,000 years and ice age terminations. AB - Oxygen isotope records from Chinese caves characterize changes in both the Asian monsoon and global climate. Here, using our new speleothem data, we extend the Chinese record to cover the full uranium/thorium dating range, that is, the past 640,000 years. The record's length and temporal precision allow us to test the idea that insolation changes caused by the Earth's precession drove the terminations of each of the last seven ice ages as well as the millennia-long intervals of reduced monsoon rainfall associated with each of the terminations. On the basis of our record's timing, the terminations are separated by four or five precession cycles, supporting the idea that the '100,000-year' ice age cycle is an average of discrete numbers of precession cycles. Furthermore, the suborbital component of monsoon rainfall variability exhibits power in both the precession and obliquity bands, and is nearly in anti-phase with summer boreal insolation. These observations indicate that insolation, in part, sets the pace of the occurrence of millennial-scale events, including those associated with terminations and 'unfinished terminations'. PMID- 27357794 TI - Seasonality of temperate forest photosynthesis and daytime respiration. AB - Terrestrial ecosystems currently offset one-quarter of anthropogenic carbon dioxide (CO2) emissions because of a slight imbalance between global terrestrial photosynthesis and respiration. Understanding what controls these two biological fluxes is therefore crucial to predicting climate change. Yet there is no way of directly measuring the photosynthesis or daytime respiration of a whole ecosystem of interacting organisms; instead, these fluxes are generally inferred from measurements of net ecosystem-atmosphere CO2 exchange (NEE), in a way that is based on assumed ecosystem-scale responses to the environment. The consequent view of temperate deciduous forests (an important CO2 sink) is that, first, ecosystem respiration is greater during the day than at night; and second, ecosystem photosynthetic light-use efficiency peaks after leaf expansion in spring and then declines, presumably because of leaf ageing or water stress. This view has underlain the development of terrestrial biosphere models used in climate prediction and of remote sensing indices of global biosphere productivity. Here, we use new isotopic instrumentation to determine ecosystem photosynthesis and daytime respiration in a temperate deciduous forest over a three-year period. We find that ecosystem respiration is lower during the day than at night-the first robust evidence of the inhibition of leaf respiration by light at the ecosystem scale. Because they do not capture this effect, standard approaches overestimate ecosystem photosynthesis and daytime respiration in the first half of the growing season at our site, and inaccurately portray ecosystem photosynthetic light-use efficiency. These findings revise our understanding of forest-atmosphere carbon exchange, and provide a basis for investigating how leaf level physiological dynamics manifest at the canopy scale in other ecosystems. PMID- 27357795 TI - Interdisciplinary research has consistently lower funding success. AB - Interdisciplinary research is widely considered a hothouse for innovation, and the only plausible approach to complex problems such as climate change. One barrier to interdisciplinary research is the widespread perception that interdisciplinary projects are less likely to be funded than those with a narrower focus. However, this commonly held belief has been difficult to evaluate objectively, partly because of lack of a comparable, quantitative measure of degree of interdisciplinarity that can be applied to funding application data. Here we compare the degree to which research proposals span disparate fields by using a biodiversity metric that captures the relative representation of different fields (balance) and their degree of difference (disparity). The Australian Research Council's Discovery Programme provides an ideal test case, because a single annual nationwide competitive grants scheme covers fundamental research in all disciplines, including arts, humanities and sciences. Using data on all 18,476 proposals submitted to the scheme over 5 consecutive years, including successful and unsuccessful applications, we show that the greater the degree of interdisciplinarity, the lower the probability of being funded. The negative impact of interdisciplinarity is significant even when number of collaborators, primary research field and type of institution are taken into account. This is the first broad-scale quantitative assessment of success rates of interdisciplinary research proposals. The interdisciplinary distance metric allows efficient evaluation of trends in research funding, and could be used to identify proposals that require assessment strategies appropriate to interdisciplinary research. PMID- 27357796 TI - Basal forebrain projections to the lateral habenula modulate aggression reward. AB - Maladaptive aggressive behaviour is associated with a number of neuropsychiatric disorders and is thought to result partly from the inappropriate activation of brain reward systems in response to aggressive or violent social stimuli. Nuclei within the ventromedial hypothalamus, extended amygdala and limbic circuits are known to encode initiation of aggression; however, little is known about the neural mechanisms that directly modulate the motivational component of aggressive behaviour. Here we established a mouse model to measure the valence of aggressive inter-male social interaction with a smaller subordinate intruder as reinforcement for the development of conditioned place preference (CPP). Aggressors develop a CPP, whereas non-aggressors develop a conditioned place aversion to the intruder-paired context. Furthermore, we identify a functional GABAergic projection from the basal forebrain (BF) to the lateral habenula (lHb) that bi-directionally controls the valence of aggressive interactions. Circuit specific silencing of GABAergic BF-lHb terminals of aggressors with halorhodopsin (NpHR3.0) increases lHb neuronal firing and abolishes CPP to the intruder-paired context. Activation of GABAergic BF-lHb terminals of non-aggressors with channelrhodopsin (ChR2) decreases lHb neuronal firing and promotes CPP to the intruder-paired context. Finally, we show that altering inhibitory transmission at BF-lHb terminals does not control the initiation of aggressive behaviour. These results demonstrate that the BF-lHb circuit has a critical role in regulating the valence of inter-male aggressive behaviour and provide novel mechanistic insight into the neural circuits modulating aggression reward processing. PMID- 27357797 TI - Coordinating cardiomyocyte interactions to direct ventricular chamber morphogenesis. AB - Many organs are composed of complex tissue walls that are structurally organized to optimize organ function. In particular, the ventricular myocardial wall of the heart comprises an outer compact layer that concentrically encircles the ridge like inner trabecular layer. Although disruption in the morphogenesis of this myocardial wall can lead to various forms of congenital heart disease and non compaction cardiomyopathies, it remains unclear how embryonic cardiomyocytes assemble to form ventricular wall layers of appropriate spatial dimensions and myocardial mass. Here we use advanced genetic and imaging tools in zebrafish to reveal an interplay between myocardial Notch and Erbb2 signalling that directs the spatial allocation of myocardial cells to their proper morphological positions in the ventricular wall. Although previous studies have shown that endocardial Notch signalling non-cell-autonomously promotes myocardial trabeculation through Erbb2 and bone morphogenetic protein (BMP) signalling, we discover that distinct ventricular cardiomyocyte clusters exhibit myocardial Notch activity that cell-autonomously inhibits Erbb2 signalling and prevents cardiomyocyte sprouting and trabeculation. Myocardial-specific Notch inactivation leads to ventricles of reduced size and increased wall thickness because of excessive trabeculae, whereas widespread myocardial Notch activity results in ventricles of increased size with a single-cell-thick wall but no trabeculae. Notably, this myocardial Notch signalling is activated non-cell-autonomously by neighbouring Erbb2-activated cardiomyocytes that sprout and form nascent trabeculae. Thus, these findings support an interactive cellular feedback process that guides the assembly of cardiomyocytes to morphologically create the ventricular myocardial wall and more broadly provide insight into the cellular dynamics of how diverse cell lineages organize to create form. PMID- 27357799 TI - Linagliptin treatment improves cerebrovascular function and remodeling and restores reduced cerebral perfusion in Type 2 diabetes. AB - The antihyperglycemic agent linagliptin, a dipeptidyl peptidase-4 (DPP-IV) inhibitor, has been shown to reduce inflammation and improve endothelial cell function. In this study, we hypothesized that DPP-IV inhibition with linagliptin would improve impaired cerebral perfusion in diabetic rats, as well as improve insulin-induced cerebrovascular relaxation and reverse pathological cerebrovascular remodeling. We further postulated that these changes would lead to a subsequent improvement of cognitive function. Male Type-2 diabetic and nondiabetic Goto-Kakizaki rats were treated with linagliptin for 4 wk, and blood glucose and DPP-IV plasma levels were assessed. Cerebral perfusion was assessed after treatment using laser-Doppler imaging, and dose response to insulin (10( 13) M-10(-6) M) in middle cerebral arteries was tested on a pressurized arteriograph. The impact of DPP-IV inhibition on diabetic cerebrovascular remodeling was assessed over a physiologically relevant pressure range, and changes in short-term hippocampus-dependent learning were observed using a novel object recognition test. Linagliptin lowered DPP-IV activity but did not change blood glucose or insulin levels in diabetes. Insulin-mediated vascular relaxation and cerebral perfusion were improved in the diabetic rats with linagliptin treatment. Indices of diabetic vascular remodeling, such as increased cross sectional area, media thickness, and wall-to-lumen ratio, were also ameliorated; however, improvements in short-term hippocampal-dependent learning were not observed. The present study provides evidence that linagliptin treatment improves cerebrovascular dysfunction and remodeling in a Type 2 model of diabetes independent of glycemic control. This has important implications in diabetic patients who are predisposed to the development of cerebrovascular complications, such as stroke and cognitive impairment. PMID- 27357801 TI - Regulation of fetal liver growth in a model of diet restriction in the pregnant rat. AB - Limited nutrient availability is a cause of intrauterine growth restriction (IUGR), a condition that has important implications for the well being of the offspring. Using the established IUGR model of maternal fasting in the rat, we investigated mechanisms that control gene expression and mRNA translation in late gestation fetal liver. Maternal fasting for 48 h during the last one-third of gestation was associated with a 10-15% reduction in fetal body weight and a disproportionate one-third reduction in total fetal liver protein. The fetal liver transcriptome showed only subtle changes consistent with reduced cell proliferation and enhanced differentiation in IUGR. Effects on the transcriptome could not be attributed to specific transcription factors. We purified translating polysomes to profile the population of mRNAs undergoing active translation. Microarray analysis of the fetal liver translatome indicated a global reduction of translation. The only targeted effect was enhanced translation of mitochondrial ribosomal proteins in IUGR, consistent with enhanced mitochondrial biogenesis. There was no evidence for attenuated signaling through the mammalian target of rapamycin (mTOR). Western blot analysis showed no changes in fetal liver mTOR signaling. However, eukaryotic initiation factor 2alpha (eIF2alpha) phosphorylation was increased in livers from IUGR fetuses, consistent with a role in global translation control. Our data indicate that IUGR-associated changes in hepatic gene expression and mRNA translation likely involve a network of complex regulatory mechanisms, some of which are novel and distinct from those that mediate the response of the liver to nutrient restriction in the adult rat. PMID- 27357802 TI - Effects of a ketogenic diet on adipose tissue, liver, and serum biomarkers in sedentary rats and rats that exercised via resisted voluntary wheel running. AB - We investigated the effects of different diets on adipose tissue, liver, serum morphology, and biomarkers in rats that voluntarily exercised. Male Sprague Dawley rats (~9-10 wk of age) exercised with resistance-loaded voluntary running wheels (EX; wheels loaded with 20-60% body mass) or remained sedentary (SED) over 6 wk. EX and SED rats were provided isocaloric amounts of either a ketogenic diet (KD; 20.2%-10.3%-69.5% protein-carbohydrate-fat), a Western diet (WD; 15.2%-42.7 42.0%), or standard chow (SC; 24.0%-58.0%-18.0%); n = 8-10 in each diet for SED and EX rats. Following the intervention, body mass and feed efficiency were lowest in KD rats, independent of exercise (P < 0.05). Absolute and relative (body mass-adjusted) omental adipose tissue (OMAT) masses were greatest in WD rats (P < 0.05), and OMAT adipocyte diameters were lowest in KD-fed rats (P < 0.05). None of the assayed OMAT or subcutaneous (SQ) protein markers were affected by the diets [total acetyl coA carboxylase (ACC), CD36, and CEBPalpha or phosphorylated NF-kappaB/p65, AMPKalpha, and hormone-sensitive lipase (HSL)], although EX unexpectedly altered some OMAT markers (i.e., higher ACC and phosphorylated NF-kappaB/p65, and lower phosphorylated AMPKalpha and phosphorylated HSL). Liver triglycerides were greatest in WD rats (P < 0.05), and liver phosphorylated NF-kappaB/p65 was lowest in KD rats (P < 0.05). Serum insulin, glucose, triglycerides, and total cholesterol were greater in WD and/or SC rats compared with KD rats (P < 0.05), and serum beta-hydroxybutyrate was greater in KD vs. SC rats (P < 0.05). In conclusion, KD rats presented a healthier metabolic profile, albeit the employed exercise protocol minimally impacts any potentiating effects that KD has on fat loss. PMID- 27357800 TI - Heat therapy promotes the expression of angiogenic regulators in human skeletal muscle. AB - Heat therapy has been shown to promote capillary growth in skeletal muscle and in the heart in several animal models, but the effects of this therapy on angiogenic signaling in humans are unknown. We evaluated the acute effect of lower body heating (LBH) and unilateral thigh heating (TH) on the expression of angiogenic regulators and heat shock proteins (HSPs) in healthy young individuals. Exposure to LBH (n = 18) increased core temperature (Tc) from 36.9 +/- 0.1 to 37.4 +/- 0.1 degrees C (P < 0.01) and average leg skin temperature (Tleg) from 33.1 +/- 0.1 to 39.6 +/- 0.1 degrees C (P < 0.01), but did not alter the levels of circulating angiogenic cytokines and bone marrow-derived proangiogenic cells (CD34(+)CD133(+)). In skeletal muscle, the change in mRNA expression from baseline of vascular endothelial growth factor (VEGF), angiopoietin 2 (ANGPT2), chemokines CCL2 and CX3CL1, platelet factor-4 (PF4), and several members of the HSP family was higher 30 min after the intervention in the individuals exposed to LBH (n = 11) compared with the control group (n = 12). LBH also reduced the expression of transcription factor FOXO1 (P = 0.03). Exposure to TH (n = 14) increased Tleg from 32.8 +/- 0.2 to 40.3 +/- 0.1 degrees C (P < 0.05) but Tc remained unaltered (36.8 +/- 0.1 degrees C at baseline and 36.9 +/- 0.1 degrees C at 90 min). This intervention upregulated the expression of VEGF, ANGPT1, ANGPT2, CCL2, and HSPs in skeletal muscle but did not affect the levels of CX3CL1, FOXO 1, and PF4. These findings suggest that both LBH and TH increase the expression of factors associated with capillary growth in human skeletal muscle. PMID- 27357803 TI - THz frequency spectrum of protein-solvent interaction energy using a recurrence plot-based Wiener-Khinchin method. AB - The dynamics of a protein and the water surrounding it are coupled via nonbonded energy interactions. This coupling can exhibit a complex, nonlinear, and nonstationary nature. The THz frequency spectrum for this interaction energy characterizes both the vibration spectrum of the water hydrogen bond network, and the frequency range of large amplitude modes of proteins. We use a Recurrence Plot based Wiener-Khinchin method RPWK to calculate this spectrum, and the results are compared to those determined using the classical auto-covariance based Wiener-Khinchin method WK. The frequency spectra for the total nonbonded interaction energy extracted from molecular dynamics simulations between the beta Lactamase Inhibitory Protein BLIP, and water molecules within a 10 A distance from the protein surface, are calculated at 150, 200, 250, and 310 K, respectively. Similar calculations are also performed for the nonbonded interaction energy between the residues 49ASP, 53TYR, and 142PHE in BLIP, with water molecules within 10 A from each residue respectively at 150, 200, 250, and 310 K. A comparison of the results shows that RPWK performs better than WK, and is able to detect some frequency data points that WK fails to detect. This points to the importance of using methods capable of taking the complex nature of the protein-solvent energy landscape into consideration, and not to rely on standard linear methods. In general, RPWK can be a valuable addition to the analysis tools for protein molecular dynamics simulations. Proteins 2016; 84:1549-1557. (c) 2016 Wiley Periodicals, Inc. PMID- 27357804 TI - Vitamin D-induced up-regulation of human keratinocyte cathelicidin anti-microbial peptide expression involves retinoid X receptor alpha. AB - The biologically active form of vitamin D, 1alpha,25-dihydroxyvitamin D3 (1,25D3), has been reported to positively regulate the human cathelicidin anti microbial peptide (CAMP) gene coding for LL-37, but the mechanisms are not completely understood. We have determined the expression of CAMP, vitamin D receptor (VDR), and the retinoid X receptor (RXR) isoforms in human skin and gingival tissue biopsies and investigated the signaling pathways involved in 1,25D3-induced upregulation of CAMP. Human skin and gingival biopsies exhibited few VDR-immunoreactive cells within the stratum basale, whereas rat colon enterocytes (positive control) possessed abundant VDR immunoreactivity. Nuclear VDR immunoreactivity was demonstrated in human skin keratinocytes (HaCaT cells). Gene analysis revealed that human skin biopsies expressed higher levels of both CAMP and RXRalpha mRNA than human gingival biopsies, whereas VDR and RXRbeta transcript levels were similar in skin and gingiva. In HaCaT cells, treatment with 1,25D3 (5 nM and 1 MUM) for 4 and 24 h up-regulated CAMP mRNA several fold, and treatment with 1,25D3 for 24 h increased protein expression of the pro-form of LL-37 (hCAP-18) by about 13 times. The 1,25D3-evoked stimulation of HaCaT CAMP expression was associated with attenuated VDR mRNA and protein expression. Treatment with RXRalpha short interfering RNA reversed the 1,25D3-induced CAMP expression in HaCaT cells, showing that RXRalpha is involved in the up-regulation of CAMP by 1,25D3. We conclude that the 1,25D3-evoked stimulation of CAMP expression in human skin keratinocytes is dependent on RXRalpha but is not associated with the up-regulation of VDR expression. PMID- 27357805 TI - Mining-Related Sediment and Soil Contamination in a Large Superfund Site: Characterization, Habitat Implications, and Remediation. AB - Historical mining activity (1850-1970) in the now inactive Tri-State Mining District provided an ongoing source of lead and zinc to the environment including the US Environmental Protection Agency Superfund site located in Cherokee County, southeast Kansas, USA. The resultant contamination adversely affected biota and caused human health problems and risks. Remediation in the Superfund site requires an understanding of the magnitude and extent of contamination. To provide some of the required information, a series of sediment and soil investigations were conducted in and near the Superfund site to characterize lead and zinc contamination in the aquatic and floodplain environments along the main stem Spring River and its major tributaries. In the Superfund site, the most pronounced lead and zinc contamination, with concentrations that far exceed sediment quality guidelines associated with potential adverse biological effects, was measured for streambed sediments and floodplain soils located within or downstream from the most intensive mining-affected areas. Tributary streambeds and floodplains in affected areas are heavily contaminated with some sites having lead and zinc concentrations that are an order of magnitude (or more) greater than the sediment quality guidelines. For the main-stem Spring River, the streambed is contaminated but the floodplain is mostly uncontaminated. Measured lead and zinc concentrations in streambed sediments, lakebed sediments, and floodplain soils documented a persistence of the post-mining contamination on a decadal timescale. These results provide a basis for the prioritization, development, and implementation of plans to remediate contamination in the affected aquatic and floodplain environments within the Superfund site. PMID- 27357806 TI - The Use of Spatial Data Infrastructure in Environmental Management:an Example from the Spatial Planning Practice in Poland. AB - Today's technology plays a crucial role in the effective use of environmental information. This includes geographic information systems and infrastructures. The purpose of this research is to identify the way in which the Polish spatial data infrastructure (PSDI) supports policies and activities that may have an impact on the environment in relation to one group of users, namely urban planners, and their tasks concerning environmental management. The study is based on a survey conducted in July and August, 2014. Moreover, the authors' expert knowledge gained through urban development practice and the analysis of the environmental conservation regulations and spatial planning in Poland has been used to define the scope of environmental management in both spatial planning studies and spatial data sources. The research included assessment of data availability, infrastructure usability, and its impact on decision-making process. The results showed that the PSDI is valuable because it allows for the acquisition of data on environmental monitoring, agricultural and aquaculture facilities. It also has a positive impact on decision-making processes and improves numerous planners' activities concerning both the inclusion of environmental indicators in spatial plans and the support of nature conservation and environmental management in the process of working on future land use. However, even though the infrastructure solves certain problems with data accessibility, further improvements might be proposed. The importance of the SDI in environmental management is noticeable and could be considered from many standpoints: Data, communities engaged in policy or decision-making concerning environmental issues, and data providers. PMID- 27357807 TI - Concern and Helplessness: Citizens' Assessments of Individual and Collective Action on the Provision of Environmental Public Goods in a Coastal City at Risk of Inundation. AB - Survey data from a representative sample of 1005 households in the UK coastal city of Portsmouth are examined to discern commonalities and contrasts in their assessment of actions to address the related environmental threats of climate change and flooding. The city of Portsmouth is at risk of inundation from rising sea levels and the city has recent experience of flooding. A simple local and global public good framework is used to organize the understanding of reported attitudes and their determinants. The findings show that it is not always the same individuals who express concern about both climate change and flooding. Investigation into perceptions of helplessness in tackling climate change indicates that individuals more often perceived themselves to be helpless in tackling climate but perceived local collective action to be more effective. Individuals considered local collective action to be more effective in tackling climate change. Perceptions of individual helplessness are in turn related to reported concern. Several socioeconomic characteristics of individuals are shown to be useful in explaining the determinants of concern and perceptions of helplessness among respondents. As other cities face climate change-related challenges, the empirical findings, based upon attitudes from an alert urban population, are informative to policy design. PMID- 27357808 TI - Human Activity and Habitat Characteristics Influence Shorebird Habitat Use and Behavior at a Vancouver Island Migratory Stopover Site. AB - Pacific Rim National Park Reserve on Vancouver Island, British Columbia, Canada, has 16 km of coastal beaches that attract many thousands of people and shorebirds (S.O. Charadrii) every year. To identify locations where shorebirds concentrate and to determine the impact of human activity and habitat characteristics on shorebirds, we conducted shorebird and visitor surveys at 20 beach sectors (across 20 total km of beach) during fall migration in 2011-2014 and spring migration in 2012 and 2013. Using zero-inflated negative binomial regression and a model selection approach, we found that beach width and number of people influenced shorebird use of beach sectors (Bayesian information criterion weight of top model = 0.69). Shorebird absence from beaches was associated with increasing number of people (parameter estimate from top model: 0.38; 95 % CI 0.19, 0.57) and decreasing beach width (parameter estimate: -0.32; 95 % CI -0.47, -0.17). Shorebirds spent more time at wider beaches (parameter estimate: 0.68; 95 % CI 0.49, 0.87). Close proximity to people increased the proportion of time shorebirds spent moving, while shorebirds spent more time moving and less time foraging on wider beaches than on narrower ones. Shorebird disturbance increased with proximity of people, activity speed, and presence of dogs. Based on our findings, management options, for reducing shorebird disturbance at Pacific Rim National Park Reserve and similar shorebird stopover areas, include mandatory buffer distances between people and shorebirds, restrictions on fast-moving activities (e.g., running, biking), prohibiting dogs, and seasonal closures of wide beach sections. PMID- 27357809 TI - River Water Pollution Status and Water Policy Scenario in Ethiopia: Raising Awareness for Better Implementation in Developing Countries. AB - Despite the increasing levels of pollution in many tropical African countries, not much is known about the strength and weaknesses of policy and institutional frameworks to tackle pollution and ecological status of rivers and their impacts on the biota. We investigated the ecological status of four large river basins using physicochemical water quality parameters and bioindicators by collecting samples from forest, agriculture, and urban landscapes of the Nile, Omo-Gibe, Tekeze, and Awash River basins in Ethiopia. We also assessed the water policy scenario to evaluate its appropriateness to prevent and control pollution. To investigate the level of understanding and implementation of regulatory frameworks and policies related to water resources, we reviewed the policy documents and conducted in-depth interviews of the stakeholders. Physicochemical and biological data revealed that there is significant water quality deterioration at the impacted sites (agriculture, coffee processing, and urban landscapes) compared to reference sites (forested landscapes) in all four basins. The analysis of legal, policy, and institutional framework showed a lack of cooperation between stakeholders, lack of knowledge of the policy documents, absence of enforcement strategies, unavailability of appropriate working guidelines, and disconnected institutional setup at the grass root level to implement the set strategies as the major problems. In conclusion, river water pollution is a growing challenge and needs urgent action to implement intersectoral collaboration for water resource management that will eventually lead toward integrated watershed management. Revision of policy and increasing the awareness and participation of implementers are vital to improve ecological quality of rivers. PMID- 27357810 TI - Has anyone been listening? Post-SPECT MPI referral rates to catheterization. PMID- 27357811 TI - Low levels of TGF-beta1 enhance human umbilical cord-derived mesenchymal stem cell fibronectin production and extend survival time in a rat model of lipopolysaccharide-induced acute lung injury. AB - Mesenchymal stem cells (MSCs) are an attractive cellular source for cell-based therapy, tissue engineering and regenerative medicine. However, the use of MSCs is limited by their low incorporation rate in the graft environment. The majority of cells are lost from the graft within 1 month, due to reduced microenvironment or local inflammation at the graft site. The extracellular matrix (ECM) may assist the survival and expansion of MSCs. The present study aimed to identify an effective approach to increase ECM expression levels by MSCs in order to enhance the therapeutic effect and survival rate of MSCs at the injury site. The concentration-dependent effect of transforming growth factor (TGF)-beta1 on human umbilical cord (hUC)-MSC proliferation and expression of ECM genes was investigated. MSCs were successfully isolated, cultured and expanded from hUC. A low concentration of TGF-beta1 (0.1 ng/ml) exhibited the optimal effect on hUC MSC proliferation and markedly stimulated the expression of ECM genes, particularly fibronectin (FN). Furthermore, treatment with TGF-beta1 caused no alteration in the immunophenotype and differentiation capacity of MSCs. In vivo experiments in rats demonstrated that intravenous injection of control UC-MSCs or TGF-beta1-pre-treated UC-MSCs reduced the severity of lipopolysaccharide-induced lung injury, assessed using histology, measurements of the wet-dry lung weight ratio, and neutrophil count and protein concentration in bronchoalveolar lavage fluid. However, the short-term (48 h) therapeutic effects of untreated and TGF beta1-pre-treated UC-MSCs were similar. The survival of MSCs in damaged lungs, determined by Sry gene expression levels, were significantly increased in MSCs pre-treated with TGF-beta1. In conclusion, pre-treatment of MSCs with a low concentration of TGF-beta1 enhanced the expression of ECM components, particularly FN, thus, improving the survival and potential therapeutic benefits of MSCs. Pre-treatment of MSCs with TGF-beta1 may prolong the effective therapy time and represent an efficient therapeutic approach for tissue repair. PMID- 27357813 TI - The effect of trastuzumab-based chemotherapy in small node-negative HER2-positive breast cancer. AB - The prognosis of patients with stage II-III Human Epidermal growth factor Receptor 2 (HER2)-positive breast cancer has significantly improved since the addition of trastuzumab to (neo-)adjuvant chemotherapy. Several reports have shown that small (<=2 cm), node-negative, HER2-positive tumors have a relatively poor prognosis and these patients increasingly receive trastuzumab-based chemotherapy. We aimed to provide evidence for this approach in a population based cohort. All T1N0M0 HER2-positive breast cancer patients diagnosed between 2006 and 2012 were identified from the Netherlands Cancer Registry. Patient, tumor, and treatment characteristics were recorded. Kaplan-Meier statistics were used for overall survival (OS) and breast cancer-specific survival (BCSS) estimations overall and in T1a, T1b, and T1c tumors separately. Cox regression analyses were performed to account for imbalances in baseline characteristics between treated and untreated patients. A total of 3512 patients were identified: 385 with T1a, 800 with T1b, and 2327 with T1c tumors. Forty-five percent of patients received chemotherapy and/or trastuzumab: 92 % received both. Chemotherapy and/or trastuzumab significantly improved 8-year OS (95 vs. 84 %; hazard ratio [HR] 0.29; 95 % confidence interval [CI] 0.21-0.41, P < 0.001). The effect remained significant in multivariable analyses (HR 0.35; 95 % CI 0.23 0.52, P < 0.001). BCSS was also improved with systemic treatment in univariable (96 vs. 92 %; HR 0.41; 95 % CI 0.27-0.63, P < 0.001) and multivariable analyses (HR 0.31; 95 % CI 0.19-0.53, P < 0.001). Treatment effect on OS and BCSS was similar in T1a, T1b, and T1c tumors. Chemotherapy and/or trastuzumab improves OS and BCSS and can be considered in all patients with small node-negative HER2 positive breast cancer. PMID- 27357812 TI - GGNBP2 acts as a tumor suppressor by inhibiting estrogen receptor alpha activity in breast cancer cells. AB - Gametogenetin-binding protein 2 (GGNBP2) is encoded in human chromosome 17q12 q23, a region known as a breast and ovarian cancer susceptibility locus. GGNBP2, also referred to ZFP403, has a single C2H2 zinc finger and a consensus LxxLL nuclear receptor-binding motif. Here, we demonstrate that GGNBP2 expression is reduced in primary human breast tumors and in breast cancer cell lines, including T47D, MCF-7, LCC9, LY2, and MDA-MB-231 compared with normal, immortalized estrogen receptor alpha (ERalpha) negative MCF-10A and MCF10F breast epithelial cells. Overexpression of GGNBP2 inhibits the proliferation of T47D and MCF-7 ERalpha positive breast cancer cells without affecting MCF-10A and MCF10F. Stable GGNBP2 overexpression in T47D cells inhibits 17beta-estradiol (E2)-stimulated proliferation as well as migration, invasion, anchorage-independent growth in vitro, and xenograft tumor growth in mice. We further demonstrate that GGNBP2 protein physically interacts with ERalpha, inhibits E2-induced activation of estrogen response element-driven reporter activity, and attenuates ER target gene expression in T47D cells. In summary, our in vitro and in vivo findings suggest that GGNBP2 is a novel breast cancer tumor suppressor functioning as a nuclear receptor corepressor to inhibit ERalpha activity and tumorigenesis. PMID- 27357814 TI - Baxter elastomeric pumps: Feasibility of weight estimates. AB - Purpose Elastomeric pumps are used to infuse a 46-h fluorouracil protocol and patients are asked to visually inspect the pump daily. The pump has a variability of +/-10% and there are additional patient variables that can increase this. The feasibility of weighing the pump rather than a visual inspection along with the secondary objective to confirm the pump's variability in real world conditions was undertaken. Methods Empty pumps were weighed using both pharmacy and kitchen scales. Pumps upon completion of the 46-h infusion were also weighed using both pharmacy and kitchen scales. Results The kitchen scale was as accurate as the pharmacy grade scale. Disconnected pumps showed the expected variability from using these infusor pumps along with a few showing greater variability likely due to patient variables. Conclusion Weighing pumps appears to be feasible both at the pharmacy and home level. Next steps would be to weigh pumps during the infusion to validate an alternate method to simple visual inspection for patients to confirm proper infusing of the pump at their home. PMID- 27357815 TI - Bortezomib therapy-related lung disease in a patient with light chain amyloidosis: A case report. AB - Bortezomib was the first antineoplastic proteasome inhibitor and is currently indicated for the treatment of hematologic malignancies including multiple myeloma and mantle cell lymphoma. This report describes a 57-year-old patient with light chain (primary) amyloidosis receiving weekly subcutaneous bortezomib injections who presented with recurrent hypoxemia and interstitial pneumonitis. Following the failure of conventional therapy, the patient responded rapidly to high-dose intravenous methylprednisolone. Oxygen therapy was able to be weaned off within three days and he was able to be discharged to home in stable condition, with follow-up computed tomography showing improving lung lesions. Bortezomib is known to rarely cause acute lung injury, but this complication has not been previously described in the setting of amyloidosis. Clinicians should be aware of potentially severe pulmonary adverse effects in all patients treated with bortezomib. PMID- 27357816 TI - Expanding the armamentarium for chronic lymphocytic leukemia: A review of novel agents in the management of chronic lymphocytic leukemia. AB - Treatment options for chronic lymphocytic leukemia, the most common leukemia in the United States, have expanded rapidly in recent years. While traditional chemoimmunotherapy still remains a mainstay for young, fit patients, a number of novel targeted therapies have emerged that have changed the therapeutic landscape. Two innovative anti-CD20 monoclonal antibodies, obinutuzumab and ofatumomamab, have demonstrated activity in chronic lymphocytic leukemia and represent well-tolerated options in upfront management of elderly patients or in those with significant comorbidities. Agents targeting the B-cell receptor pathway, ibrutinib and idelalisib, have excellent activity in chronic lymphocytic leukemia, particularly in those patients with 17p deletions, in which responses to chemoimmunotherapy are traditionally dismal. Venetoclax (ABT-199), the recently FDA-approved BCL2 inhibitor, as well as several other agents and therapy combinations in the pipeline offer great promise for patients with chronic lymphocytic leukemia, particularly in the relapsed/refractory setting. This article comprehensively reviews the data for novel agents in chronic lymphocytic leukemia, including the pharmacology of therapies, unique toxicities, and other practical management considerations for clinicians. PMID- 27357817 TI - An update on current and emerging therapies for epithelial ovarian cancer: Focus on poly(adenosine diphosphate-ribose) polymerase inhibition and antiangiogenesis. AB - Epithelial ovarian cancer is the leading cause of death from gynecologic tumors in western countries. Newly diagnosed epithelial ovarian cancer patients usually have good initial response to combination of platinum-based and taxane-based chemotherapy. However, most patients eventually experience relapses, and responses to subsequent therapies are generally short-lived. Intraperitoneal chemotherapy has been shown to improve survival outcomes, but toxicities and logistics limit its acceptance. Dose-dense schedule of paclitaxel combined with carboplatin remains controversial, and more studies are needed to validate this approach. About 15% of epithelial ovarian cancer patients carry gene mutations in BRCA1 and/or BRCA2. The development of poly(adenosine diphosphate-ribose) polymerase inhibitors represents a novel therapeutic strategy, in which poly(adenosine diphosphate-ribose) inhibition leads to the formation of double stranded DNA breaks that cannot be accurately repaired in BRCA1- or BRCA2-mutated tumors, thus leading to tumor cell death. This principle of synthetic lethality can be demonstrated by olaparib, an oral agent that inhibits the repair of single strand DNA breaks during DNA replication, causing defective homologous recombination and hence tumor cell death. Currently, many poly(adenosine diphosphate-ribose) inhibitors are in different phases of development. Furthermore, mechanisms of defective homologous recombination pathway may include other genetic and epigenetic abnormalities in addition to either germline or somatic BRCA1 and/or BRCA2 mutations, making these pathways as potential therapeutic targets. The clinical pharmacology, clinical efficacy, safety, administration issues of olaparib and current clinical development of poly(adenosine diphosphate-ribose) inhibitors are described in this article, along with an overview on the treatment options (including intraperitoneal chemotherapy and dose-dense chemotherapy) for epithelial ovarian cancer. On the other hand, overexpression of the vascular endothelial growth factor and increased angiogenesis are associated with the development and progression of epithelial ovarian cancer. Although there are some expected toxicities associated with antiangiogenesis, combination of bevacizumab and systemic chemotherapy improves the progression-free survival and response rate compared to chemotherapy alone. The clinical efficacy of adding bevacizumab and its safety for advanced epithelial ovarian cancer is also reviewed, with emerging data on antiangiogenesis therapy. PMID- 27357818 TI - Haplotype analysis reveals that the recurrent BRCA1 deletion of exons 23 and 24 is a Greek founder mutation. AB - A recurrent large genomic rearrangement (LGR) encompassing exons 23 and 24 of the BRCA1 gene has been identified in breast-ovarian cancer families of Greek origin. Its breakpoints have been determined as c.5406 + 664_*8273del11052 (RefSeq: NM_007294.3) and a diagnostic polymerase chain reaction (PCR) has been set up for rapid screening. In a series of 2,092 high-risk families completely screened for BRCA1 and BRCA2 germline mutations, we have found the deletion in 35 families (1.68%), representing 7.83% of the mutations identified in both genes and 10.3% of the total BRCA1 mutations. In order to characterize this deletion as a founder mutation, haplotype analysis was conducted in 60 carriers from 35 families, using three BRCA1 intragenic microsatellite markers and four markers surrounding the BRCA1 locus. Our results demonstrate a common shared core disease-associated haplotype of 2.89Mb. Our calculations estimate that the deletion has originated from a common ancestor 1450 years ago, which most probably inhabited the Asia Minor area. The particular (LGR) is the third mutation of such type that is proven to have a Greek founder effect in the Greek population, illustrating the necessity for LGRs testing in individuals of Greek descent. PMID- 27357819 TI - Stigma by association and family burden among family members of people with mental illness: the mediating role of coping. AB - PURPOSE: When someone has a mental illness, family members may share the experience of stigma. Past research has established that family members' experiences of stigma by association predict psychological distress and lower quality-of-life. METHODS: The present study, conducted with 503 family members of people with mental illness examined the prevalence of 14 different coping strategies. Of greater importance, we examined the role of these coping strategies as mediators of the relationships between stigma by association and family burden, on the one hand, and outcomes, such as psychological distress and quality-of-life, on the other. RESULTS: The results showed that both perceived stigma by association and family burden are associated with greater psychological distress and lower quality-of-life, and that most coping strategies mediate these relationships. CONCLUSIONS: Adaptive coping strategies were related to reduced negative outcomes, while most maladaptive coping strategies were related to enhanced negative outcomes. Implications for intervention development are discussed. PMID- 27357820 TI - Attitudes towards the people with mental illness: comparison between Czech medical doctors and general population. AB - PURPOSE: Stigma among health care professionals is detrimental to the life of those with mental health problems. In the region of post-communist Europe, the level of stigma among health care providers remains understudied. We aimed to compare attitudes towards people with mental illness between Czech medical doctors and the general population. METHODS: The Community Attitudes towards Mentally Ill (CAMI) scale was used to measure stigmatizing attitudes among a nationally representative sample of (1) adults residing in the Czech Republic (n = 1810) and (2) Czech medical doctors (n = 1200). Descriptive statistics and multivariable linear regression were used to assess differences between both samples. RESULTS: Compared to the general adult population in the Czech Republic, Czech medical doctors demonstrated less stigmatizing attitudes toward people with mental illness in 26 of the 27 CAMI items as well as in the total CAMI score. Medical doctors, however, were more likely to consider mental hospitals as an up to-date method of treating people with mental illness. CONCLUSIONS: Our findings demonstrate more favourable attitudes towards people with mental illness among Czech medical doctors when compared to the Czech general population. Stigma, however, is high among both these groups. PMID- 27357822 TI - Clinical outcomes after rescue extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest. AB - AIM: Extracorporeal cardiopulmonary resuscitation (ECPR) has been shown to have survival benefit in patients who had in-hospital cardiac arrest (IHCA). However, limited data are available on the role of extracorporeal membrane oxygenation (ECMO) for out-of-hospital cardiac arrest (OHCA). Therefore, we aimed to investigate clinical outcomes and predictors of in-hospital mortality in patients who had OHCA and who underwent ECPR. METHODS: From January 2004 to December 2013, 235 patients who received ECPR were enrolled in a retrospective, single-centre, observational registry. Among those, we studied 35 adult patients who had OHCA. The primary outcome was in-hospital mortality. RESULTS: Among 35 patients with a median age of 55 years (IQR 45-64), 29 (82.9%) of whom were male, ECMO implantation was successful in all and 10 patients (28.6%) lived to be discharged from the hospital. In 18 cases (51.4%), first monitored rhythms were identified as ventricular tachycardia/ventricular fibrillation, that is, shockable rhythm. There were no differences between in-hospital survivors and non-survivors regarding median time of arrest to cardiopulmonary resuscitation (CPR) (survivors: 23.5 min (IQR 18.8-27.3) vs non-survivors: 20.0 min (IQR 15.0-24.5); p=0.41) and median time of CPR to ECMO pump-on (survivors: 61.0 min (IQR 39.8 77.8) vs non-survivors 50.0 min (IQR 44.0-72.5); p=0.50). In 23 cases (65.7%), ischaemic heart disease was diagnosed and successful revascularisation was achieved in a significantly higher proportion of the survivor group (8/10 (80.0%)) than the non-survivor group (8/25 (32.0%)) (p=0.02). Witnessed arrest (HR=3.96; 95% CI 1.38 to 11.41; p=0.01), bystander CPR (HR=4.05; 95% CI 1.56 to 10.42; p=0.004) and successful revascularisation (HR=2.90; 95% CI 1.23 to 6.86; p=0.02) were independent predictors of survival-to-discharge in patients who had OHCA in univariate Cox regression analysis. CONCLUSION: Survival rate for ECPR in the setting of OHCA remains poor. Our findings suggest that ECMO implantation should be very carefully considered in highly selected patients who had OHCA with little no-flow time and a reversible cause. PMID- 27357821 TI - What shapes 7-year-olds' subjective well-being? Prospective analysis of early childhood and parenting using the Growing Up in Scotland study. AB - PURPOSE: Research on predictors of young children's psychosocial well-being currently relies on adult-reported outcomes. This study investigated whether early family circumstances and parenting predict 7-year-olds' subjective well being. METHODS: Information on supportive friendships, liking school and life satisfaction was obtained from 7-year-olds in one Growing Up in Scotland birth cohort in 2012-2013 (N = 2869). Mothers provided information on early childhood factors from 10 to 34 months, parenting (dysfunctional parenting, home learning and protectiveness) from 46 to 70 months, and 7-year-olds' adjustment. Multivariable path models explored associations between early childhood factors, parenting and 7-year-olds' subjective well-being. Supplementary analyses compared findings with those for mother-reported adjustment. RESULTS: In a model of early childhood factors, maternal distress predicted less supportive friendships and lower life satisfaction (coefficients -0.12), poverty predicted less supportive friendships (-0.09) and remote location predicted all outcomes (-0.20 to -0.27). In a model with parenting added, dysfunctional parenting predicted all outcomes ( 10 to -0.16), home learning predicted liking school (0.11) and life satisfaction (0.08), and protectiveness predicted life satisfaction (0.08). Effects of maternal distress were fully mediated, largely via dysfunctional parenting, while home learning mediated negative effects of low maternal education. Direct effects of poverty and remote location remained. Findings for mother-reported child adjustment were broadly similar. CONCLUSIONS: Unique prospective data show parenting and early childhood impact 7-year-olds' subjective well-being. They underline the benefits for children of targeting parental mental health and dysfunctional parenting, and helping parents develop skills to support children at home and school. PMID- 27357823 TI - Simultaneous Biosynthesis of Polyhydroxyalkanoates and Extracellular Polymeric Substance (EPS) from Crude Glycerol from Biodiesel Production by Different Bacterial Strains. AB - Simultaneous synthesis of polyhydroxyalkanoates (PHAs) and polyglutamic acid (PGA) was investigated in cultures of Cupriavidus necator IPT 026, C. necator IPT 027, C. necator IPT 029, and Bacillus megaterium INCQS 425 strains in a medium containing 2.0 % sucrose or crude glycerol from biodiesel (CGB), in an orbital shaker (35 degrees C, 180 rpm, 72 h). All the strains tested simultaneously produced PHA and PGA in a medium containing CGB. The C. necator IPT026 culture provided higher molecular mass PHA and PGA (1128.55 and 835.56 kDa, respectively). B. megaterium INCQS 425 promoted PGA production (1.90 g L-1) with higher crystalline melting temperature (84.04 degrees C) and higher initial decomposition temperature (247.10 degrees C). Furthermore, the latter culture promoted the production of medium- and long-chain PHA (0.78 g L-1) with high crystalline melting temperatures (~170 degrees C) and high initial decomposition temperature (307.53 degrees C) and low degree of crystallinity (20.2 %). These characteristics render these PHAs more appropriate and suitable for processes that require high temperatures, such as extrusion, increasing the possibility of industrial applications, especially in the packaging sector. PMID- 27357824 TI - Proteomic analysis of breast tumors confirms the mRNA intrinsic molecular subtypes using different classifiers: a large-scale analysis of fresh frozen tissue samples. AB - BACKGROUND: Breast cancer is a complex and heterogeneous disease that is usually characterized by histological parameters such as tumor size, cellular arrangements/rearrangments, necrosis, nuclear grade and the mitotic index, leading to a set of around twenty subtypes. Together with clinical markers such as hormone receptor status, this classification has considerable prognostic value but there is a large variation in patient response to therapy. Gene expression profiling has provided molecular profiles characteristic of distinct subtypes of breast cancer that reflect the divergent cellular origins and degree of progression. METHODS: Here we present a large-scale proteomic and transcriptomic profiling study of 477 sporadic and hereditary breast cancer tumors with matching mRNA expression analysis. Unsupervised hierarchal clustering was performed and selected proteins from large-scale tandem mass spectrometry (MS/MS) analysis were transferred into a highly multiplexed targeted selected reaction monitoring assay to classify tumors using a hierarchal cluster and support vector machine with leave one out cross-validation. RESULTS: The subgroups formed upon unsupervised clustering agree very well with groups found at transcriptional level; however, the classifiers (genes or their respective protein products) differ almost entirely between the two datasets. In-depth analysis shows clear differences in pathways unique to each type, which may lie behind their different clinical outcomes. Targeted mass spectrometry analysis and supervised clustering correlate very well with subgroups determined by RNA classification and show convincing agreement with clinical parameters. CONCLUSIONS: This work demonstrates the merits of protein expression profiling for breast cancer stratification. These findings have important implications for the use of genomics and expression analysis for the prediction of protein expression, such as receptor status and drug target expression. The highly multiplexed MS assay is easily implemented in standard clinical chemistry practice, allowing rapid and cheap characterization of tumor tissue suitable for directing the choice of treatment. PMID- 27357825 TI - Sparse single-step method for genomic evaluation in pigs. AB - BACKGROUND: In many animal breeding programs, with the increasing number of genotyped animals, estimation of genomic breeding values by the single-step method is becoming limited by excessive computing requirements. A recently proposed algorithm for proven and young animals (APY) is an approximation that reduces computing time drastically by dividing genotyped animals into core and non-core animals, with only computations for core animals being time-consuming. We hypothesized that choosing core animals based on representing all generations, minimizing the relatedness within the core group, or maximizing the number of genotyped offspring, would result in greater accuracies of estimated breeding values (EBV). METHODS: We compared eight different core groups for the three pig breeds DanAvl Duroc, DanAvl Landrace and DanAvl Yorkshire. These eight sparse approximations of the single-step method were evaluated based on correlations of EBV for genotyped animals obtained from the sparse methods with those obtained from the usual version of the single-step method. We used a single-trait model with daily gain as trait. RESULTS: For core groups that distributed animals across generations, correlations for genotyped animals (from 0.977 to 0.989) were higher than for those that did not distribute core animals across generations (from 0.934 to 0.956). For core groups that maximized the number of genotyped offspring, correlations for genotyped animals (from 0.983 to 0.989) were higher than for other core groups (from 0.934 to 0.981). There was no clear association between low relatedness within the core group and accuracy of approximations. CONCLUSIONS: We found that for core groups that represent all generations and that maximize the number of genotyped offspring, accurate approximations of EBV were obtained. However, we did not find a clear association between accuracy and relatedness within the core group. For the APY method, this is the first study that reports systematic criteria for the creation of core groups that result in more accurate EBV than a similar-sized random core group. Random core groups only ensure across-generation representation. Therefore, we recommend choosing a core group that represents all generations and that maximizes the number of genotyped offspring for single-step genomic evaluation using the APY method. PMID- 27357826 TI - MCD diet-induced steatohepatitis is associated with alterations in asymmetric dimethylarginine (ADMA) and its transporters. AB - Using an experimental model of NASH induced by a methionine-choline-deficient (MCD) diet, we investigated whether changes occur in serum and tissue levels of asymmetric dimethylarginine (ADMA). Male Wistar rats underwent NASH induced by 8 week feeding with an MCD diet. Serum and hepatic biopsies at 2, 4 and 8 weeks were taken, and serum enzymes, ADMA and nitrate/nitrite (NOx), were evaluated. Hepatic biopsies were used for mRNA and protein expression analysis of dimethylarginine dimethylaminohydrolase-1 (DDAH-1) and protein methyltransferases (PRMT-1), enzymes involved in ADMA metabolism and synthesis, respectively, and ADMA transporters (CAT-1, CAT-2A and CAT-2B). Lipid peroxides (TBARS), glutathione, ATP/ADP and DDAH activity were quantified. An increase in serum AST and ALT was detected in MCD animals. A time-dependent decrease in serum and tissue ADMA and increase in mRNA expression of DDAH-1 and PRMT-1 as well as higher rates of mRNA expression of CAT-1 and lower rates of CAT-2A and CAT-2B were found after 8-week MCD diet. An increase in serum NOx and no changes in protein expression in DDAH-1 and CAT-1 and higher content in CAT-2 and PRMT-1 were found at 8 weeks. Hepatic DDAH activity decreased with a concomitant increase in oxidative stress, as demonstrated by high TBARS levels and low glutathione content. In conclusion, a decrease in serum and tissue ADMA levels in the MCD rats was found associated with a reduction in DDAH activity due to the marked oxidative stress observed. Changes in ADMA levels and its transporters are innovative factors in the onset and progression of hepatic alterations correlated with MCD diet-induced NASH. PMID- 27357827 TI - Salidroside protects cortical neurons against glutamate-induced cytotoxicity by inhibiting autophagy. AB - Recent evidence suggests that glutamate-induced cytotoxicity contributes to autophagic neuron death and is partially mediated by increased oxidative stress. Salidroside has been demonstrated to have neuroprotective effects in glutamate induced neuronal damage. The precise mechanism of its regulatory role in neuronal autophagy is, however, poorly understood. This study aimed to probe the effects and mechanisms of salidroside in glutamate-induced autophagy activation in cultured rat cortical neurons. Cell viability assay, Western blotting, coimmunoprecipitation, and small interfering RNA were performed to analyze autophagy activities during glutamate-evoked oxidative injury. We found that salidroside protected neonatal neurons from glutamate-induced apoptotic cell death. Salidroside significantly attenuated the LC3-II/LC3-I ratio and expression of Beclin-1, but increased (SQSTM1)/p62 expression under glutamate exposure. Pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, decreased LC3 II/LC3-I ratio, attenuated glutamate-induced cell injury, and mimicked some of the protective effects of salidroside against glutamate-induced cell injury. Molecular analysis demonstrated that salidroside inhibited cortical neuron autophagy in response to glutamate exposure through p53 signaling by increasing the accumulation of cytoplasmic p53. Salidroside inhibited the glutamate-induced dissociation of the Bcl-2-Beclin-1 complex with minor affects on the PI3K/Akt/mTOR signaling pathways. These data demonstrate that the inhibition of autophagy could be responsible for the neuroprotective effects of salidroside on glutamate-induced neuronal injury. PMID- 27357828 TI - Modulatory effects of vagal stimulation on neurophysiological parameters and the cellular immune response in the rat brain during systemic inflammation. AB - BACKGROUND: Stimulation of the vagus nerve has modulating, anti-inflammatory effects on the cellular immune response in the blood and the spleen, stabilizing brain function. Here, we aimed to investigate its potential effects on immune-to brain communication focusing on neurophysiological readouts and leukocyte migration to the brain during severe sepsis-like endotoxemia. METHODS: Systemic inflammation was induced by intravenous administration of lipopolysaccharide (LPS; 5 mg/kg). Animals received either no manipulation of the vagus nerve, vagotomy, or vagotomy plus vagus nerve stimulation of the distal trunk. Somatosensory evoked potentials and evoked flow velocity response were measured for 4.5 h as indicators of brain function and neurovascular coupling, respectively. In addition, brain areas with (cortex) and without (hypothalamus) tight blood-brain barrier were studied separately using immunohistochemistry and RT-PCR. Moreover, plasma cytokine and leptin levels were analyzed by ELISA. RESULTS: LPS induced a decline of both neurophysiological parameters, which was prevented by vagus nerve stimulation. As for peripheral organs, LPS-stimulated neutrophil counts increased in the brain and colocalized in the brain with endothelial intercellular adhesion molecule (ICAM)-1. Interestingly, vagal stimulation reduced this colocalization and decreased nuclear translocation of the brain cell activation marker nuclear factor interleukin 6 (NF-IL6). Furthermore, it reduced the gene expression of inflammatory markers and extravasation signals (IL-6, CXCL-1, ICAM-1) in the hypothalamus but not the cortex linked to a moderate decrease in circulating cytokine levels (interleukin 6, tumor necrosis factor alpha) as well as lower plasma leptin concentration. CONCLUSIONS: Our data suggest beneficial effects of anti-inflammatory vagus nerve stimulation on brain function by reducing the interaction of neurotrophil granulocytes with the brain endothelium as well as attenuating inflammatory responses in brain areas lacking a blood-brain barrier. PMID- 27357829 TI - Availability and quality of routine morbidity data: review of studies in South Africa. AB - Objectives: Routine health information systems (RHISs) provide data that are vital for planning and monitoring individual health. Data from RHISs could also be used for purposes for which they were not originally intended, provided that the data are of sufficient quality. For example, morbidity data could be used to inform burden of disease estimations, which serve as important evidence to prioritize interventions and promote health. The objective of this study was to identify and assess published quantitative assessments of data quality related to patient morbidity in RHISs in use in South Africa. Materials and Methods: We conducted a review of literature published between 1994 and 2014 that assessed the quality of data in RHISs in South Africa. World Health Organization (WHO) data quality components were used as the assessment criteria. Results: Of 420 references identified, 11 studies met the inclusion criteria. The studies were limited to tuberculosis and HIV. No study reported more than 3 WHO data quality components or provided a quantitative assessment of quality that could be used for burden of disease estimation. Discussion: The included studies had limited geographical focus and evaluated different source data at different levels of the information system. All studies reported poor data quality. Conclusion: This review confirmed concerns about the quality of data in RHISs, and highlighted the need for a comprehensive evaluation of the quality of patient-level morbidity data in RHISs in South Africa. PMID- 27357830 TI - Acute care patient portals: a qualitative study of stakeholder perspectives on current practices. AB - Objective: To describe current practices and stakeholder perspectives of patient portals in the acute care setting. We aimed to: (1) identify key features, (2) recognize challenges, (3) understand current practices for design, configuration, and use, and (4) propose new directions for investigation and innovation. Materials and Methods: Mixed methods including surveys, interviews, focus groups, and site visits with stakeholders at leading academic medical centers. Thematic analyses to inform development of an explanatory model and recommendations. Results: Site surveys were administered to 5 institutions. Thirty interviews/focus groups were conducted at 4 site visits that included a total of 84 participants. Ten themes regarding content and functionality, engagement and culture, and access and security were identified, from which an explanatory model of current practices was developed. Key features included clinical data, messaging, glossary, patient education, patient personalization and family engagement tools, and tiered displays. Four actionable recommendations were identified by group consensus. Discussion: Design, development, and implementation of acute care patient portals should consider: (1) providing a single integrated experience across care settings, (2) humanizing the patient clinician relationship via personalization tools, (3) providing equitable access, and (4) creating a clear organizational mission and strategy to achieve outcomes of interest. Conclusion: Portals should provide a single integrated experience across the inpatient and ambulatory settings. Core functionality includes tools that facilitate communication, personalize the patient, and deliver education to advance safe, coordinated, and dignified patient-centered care. Our findings can be used to inform a "road map" for future work related to acute care patient portals. PMID- 27357831 TI - Comparison of accuracy of physical examination findings in initial progress notes between paper charts and a newly implemented electronic health record. AB - INTRODUCTION: There have been several concerns about the quality of documentation in electronic health records (EHRs) when compared to paper charts. This study compares the accuracy of physical examination findings documentation between the two in initial progress notes. METHODOLOGY: Initial progress notes from patients with 5 specific diagnoses with invariable physical findings admitted to Beaumont Hospital, Royal Oak, between August 2011 and July 2013 were randomly selected for this study. A total of 500 progress notes were retrospectively reviewed. The paper chart arm consisted of progress notes completed prior to the transition to an EHR on July 1, 2012. The remaining charts were placed in the EHR arm. The primary endpoints were accuracy, inaccuracy, and omission of information. Secondary endpoints were time of initiation of progress note, word count, number of systems documented, and accuracy based on level of training. RESULTS: The rate of inaccurate documentation was significantly higher in the EHRs compared to the paper charts (24.4% vs 4.4%). However, expected physical examination findings were more likely to be omitted in the paper notes compared to EHRs (41.2% vs 17.6%). Resident physicians had a smaller number of inaccuracies (5.3% vs 17.3%) and omissions (16.8% vs 33.9%) compared to attending physicians. CONCLUSIONS: During the initial phase of implementation of an EHR, inaccuracies were more common in progress notes in the EHR compared to the paper charts. Residents had a lower rate of inaccuracies and omissions compared to attending physicians. Further research is needed to identify training methods and incentives that can reduce inaccuracies in EHRs during initial implementation. PMID- 27357832 TI - Predicting mortality over different time horizons: which data elements are needed? AB - OBJECTIVE: Electronic health records (EHRs) are a resource for "big data" analytics, containing a variety of data elements. We investigate how different categories of information contribute to prediction of mortality over different time horizons among patients undergoing hemodialysis treatment. MATERIAL AND METHODS: We derived prediction models for mortality over 7 time horizons using EHR data on older patients from a national chain of dialysis clinics linked with administrative data using LASSO (least absolute shrinkage and selection operator) regression. We assessed how different categories of information relate to risk assessment and compared discrete models to time-to-event models. RESULTS: The best predictors used all the available data (c-statistic ranged from 0.72-0.76), with stronger models in the near term. While different variable groups showed different utility, exclusion of any particular group did not lead to a meaningfully different risk assessment. Discrete time models performed better than time-to-event models. CONCLUSIONS: Different variable groups were predictive over different time horizons, with vital signs most predictive for near-term mortality and demographic and comorbidities more important in long-term mortality. PMID- 27357833 TI - Translating evidence to practice in the health professions: a randomized trial of Twitter vs Facebook. AB - Objective: Our objective was to compare the change in research informed knowledge of health professionals and their intended practice following exposure to research information delivered by either Twitter or Facebook. Methods: This open label comparative design study randomized health professional clinicians to receive "practice points" on tendinopathy management via Twitter or Facebook. Evaluated outcomes included knowledge change and self-reported changes to clinical practice. Results: Four hundred and ninety-four participants were randomized to 1 of 2 groups and 317 responders analyzed. Both groups demonstrated improvements in knowledge and reported changes to clinical practice. There was no statistical difference between groups for the outcomes of knowledge change (P = .728), changes to clinical practice (P = .11) or the increased use of research information (P = .89). Practice points were shared more by the Twitter group (P < .001); attrition was lower in the Facebook group (P < .001). Conclusion: Research information delivered by either Twitter or Facebook can improve clinician knowledge and promote behavior change. No differences in these outcomes were observed between the Twitter and Facebook groups. Brief social media posts are as effective as longer posts for improving knowledge and promoting behavior change. Twitter may be more useful in publicizing information and Facebook for encouraging course completion. PMID- 27357834 TI - Low tuberculosis case detection: a community and health facility based study of contributory factors in the Nkwanta South district of Ghana. AB - BACKGROUND: Tuberculosis (TB) continues to pose a major public health problem globally. In Ghana, the national TB case detection rate is 81 %; however, some districts are not able to meet their case detection targets. This study was therefore carried out in the Nkwanta South district to identify possible factors contributing to low TB case detection. METHODS: A cross sectional descriptive study involving the review of outpatients records for the year 2012 was conducted. Data on cough for 2 weeks or more duration, age, sex, area of residence and sputum smear examination were extracted. A community-based survey involving household contacts of TB patients and community based volunteers was also carried out. Data collected in the community included knowledge of TB status of relatives, level of socialization with TB patients and signs and symptoms of TB disease. Descriptive statistics including cross-tabulations were used to identify possible factors contributing to low TB case detection. RESULTS: A total of 932 patients out of 3987 reported coughing for 2 weeks or more (23.4 %; 932/3987). Out of that, only 24.6 % (230/932) had sputum smear microscopy done, yielding 57 (24.8 %) positive cases. Five out of the 57 positive cases were found not registered for the initiation of treatment leading to a false primary default rate of 8.8 % per year. Eighty-five percent of the contacts were able to mention persistent cough as a sign/symptom of TB with 80.4 % indicating that TB can be cured. Only 10 % of health facilities provided diagnostic services in the district with only 25 % of staff having had training in TB management. CONCLUSION: The study identified some factors (weak record review systems, inadequate diagnostic centres, lack of trained persons and some level of stigma at the community level) that could be contributing to low TB case detection in the Nkwanta South district. PMID- 27357835 TI - Adoption of a Portal for the Primary Care Management of Pediatric Asthma: A Mixed Methods Implementation Study. AB - BACKGROUND: Patient portals may improve communication between families of children with asthma and their primary care providers and improve outcomes. However, the feasibility of using portals to collect patient-reported outcomes from families and the barriers and facilitators of portal implementation across diverse pediatric primary care settings have not been established. OBJECTIVE: We evaluated the feasibility of using a patient portal for pediatric asthma in primary care, its impact on management, and barriers and facilitators of implementation success. METHODS: We conducted a mixed-methods implementation study in 20 practices (11 states). Using the portal, parents of children with asthma aged 6-12 years completed monthly surveys to communicate treatment concerns, treatment goals, symptom control, medication use, and side effects. We used logistic regression to evaluate the association of portal use with child characteristics and changes to asthma management. Ten clinician focus groups and 22 semistructured parent interviews explored barriers and facilitators of use in the context of an evidence-based implementation framework. RESULTS: We invited 9133 families to enroll and 237 (2.59%) used the portal (range by practice, 0.6% 13.6%). Children of parents or guardians who used the portal were significantly more likely than nonusers to be aged 6-9 years (vs 10-12, P=.02), have mild or moderate/severe persistent asthma (P=.009 and P=.04), have a prescription of a controller medication (P<.001), and have private insurance (P=.002). Portal users with uncontrolled asthma had significantly more medication changes and primary care asthma visits after using the portal relative to the year earlier (increases of 14% and 16%, respectively). Qualitative results revealed the importance of practice organization (coordinated workflows) as well as family (asthma severity) and innovation (facilitated communication and ease of use) characteristics for implementation success. CONCLUSIONS: Although use was associated with higher treatment engagement, our results suggest that achieving widespread portal adoption is unlikely in the short term. Implementation efforts should include workflow redesign and prioritize enrollment of symptomatic children. CLINICALTRIAL: Clinicaltrials.gov NCT01966068; https://clinicaltrials.gov/ct2/show/NCT01966068 (Archived by WebCite at http://www.webcitation.org/6i9iSQkm3). PMID- 27357837 TI - Reply to the letter to the editor. PMID- 27357836 TI - Exploring pig trade patterns to inform the design of risk-based disease surveillance and control strategies. AB - An understanding of the patterns of animal contact networks provides essential information for the design of risk-based animal disease surveillance and control strategies. This study characterises pig movements throughout England and Wales between 2009 and 2013 with a view to characterising spatial and temporal patterns, network topology and trade communities. Data were extracted from the Animal and Plant Health Agency (APHA)'s RADAR (Rapid Analysis and Detection of Animal-related Risks) database, and analysed using descriptive and network approaches. A total of 61,937,855 pigs were moved through 872,493 movements of batches in England and Wales during the 5-year study period. Results show that the network exhibited scale-free and small-world topologies, indicating the potential for diseases to quickly spread within the pig industry. The findings also provide suggestions for how risk-based surveillance strategies could be optimised in the country by taking account of highly connected holdings, geographical regions and time periods with the greatest number of movements and pigs moved, as these are likely to be at higher risk for disease introduction. This study is also the first attempt to identify trade communities in the country, information which could be used to facilitate the pig trade and maintain disease-free status across the country in the event of an outbreak. PMID- 27357838 TI - The effect of hypohydration on endothelial function in healthy adults. PMID- 27357839 TI - KinMutRF: a random forest classifier of sequence variants in the human protein kinase superfamily. AB - BACKGROUND: The association between aberrant signal processing by protein kinases and human diseases such as cancer was established long time ago. However, understanding the link between sequence variants in the protein kinase superfamily and the mechanistic complex traits at the molecular level remains challenging: cells tolerate most genomic alterations and only a minor fraction disrupt molecular function sufficiently and drive disease. RESULTS: KinMutRF is a novel random-forest method to automatically identify pathogenic variants in human kinases. Twenty six decision trees implemented as a random forest ponder a battery of features that characterize the variants: a) at the gene level, including membership to a Kinbase group and Gene Ontology terms; b) at the PFAM domain level; and c) at the residue level, the types of amino acids involved, changes in biochemical properties, functional annotations from UniProt, Phospho.ELM and FireDB. KinMutRF identifies disease-associated variants satisfactorily (Acc: 0.88, Prec:0.82, Rec:0.75, F-score:0.78, MCC:0.68) when trained and cross-validated with the 3689 human kinase variants from UniProt that have been annotated as neutral or pathogenic. All unclassified variants were excluded from the training set. Furthermore, KinMutRF is discussed with respect to two independent kinase-specific sets of mutations no included in the training and testing, Kin-Driver (643 variants) and Pon-BTK (1495 variants). Moreover, we provide predictions for the 848 protein kinase variants in UniProt that remained unclassified. A public implementation of KinMutRF, including documentation and examples, is available online ( http://kinmut2.bioinfo.cnio.es ). The source code for local installation is released under a GPL version 3 license, and can be downloaded from https://github.com/Rbbt-Workflows/KinMut2 . CONCLUSIONS: KinMutRF is capable of classifying kinase variation with good performance. Predictions by KinMutRF compare favorably in a benchmark with other state-of-the-art methods (i.e. SIFT, Polyphen-2, MutationAssesor, MutationTaster, LRT, CADD, FATHMM, and VEST). Kinase-specific features rank as the most elucidatory in terms of information gain and are likely the improvement in prediction performance. This advocates for the development of family-specific classifiers able to exploit the discriminatory power of features unique to individual protein families. PMID- 27357840 TI - Community perceptions of pre-eclampsia and eclampsia in southern Mozambique. AB - BACKGROUND: Sub-Saharan Africa has the highest maternal mortality ratio at 500 deaths per 100,000 live births. In Mozambique maternal mortality is estimated at 249-480 per 100,000 live births and eclampsia is the third leading cause of death. The objective of this study was to describe the community understanding of pre-eclampsia and eclampsia, as a crucial step to improve maternal and perinatal health in southern Mozambique. METHODS: This qualitative study was conducted in Maputo and Gaza Provinces of southern Mozambique. Twenty focus groups were convened with pregnant women, partners and husbands, matrons and traditional birth attendants, and mothers and mothers-in-law. In addition, ten interviews were conducted with traditional healers, matrons, and a traditional birth attendant. All discussions were audio-recorded, translated from local language (Changana) to Portuguese and transcribed verbatim prior to analysis with QSR NVivo 10. A thematic analysis approach was taken. RESULTS: The conditions of "pre eclampsia" and "eclampsia" were not known in these communities; however, participants were familiar with hypertension and seizures in pregnancy. Terms linked with the biomedical concept of pre-eclampsia were high blood pressure, fainting disease and illness of the heart, whereas illness of the moon, snake illness, falling disease, childhood illness, illness of scaresand epilepsy were used to characterizeeclampsia. The causes of hypertension in pregnancy were thought to include mistreatment by in-laws, marital problems, and excessive worrying. Seizures in pregnancy were believed to be caused by a snake living inside the woman's body. Warning signs thought to be common to both conditions were headache, chest pain, weakness, dizziness, fainting, sweating, and swollen feet. CONCLUSION: Local beliefs in southern Mozambique, regarding the causes, presentation, outcomes and treatment of pre-eclampsia and eclampsia were not aligned with the biomedical perspective. The community was often unaware of the link between hypertension and seizures in pregnancy. The numerous widespread myths and misconceptions concerning pre-eclampsia and eclampsiamay induceinappropriatetreatment-seeking and demonstrate a need for increased community education regarding pregnancy and associated complications. TRIAL REGISTRATION: NCT01911494. PMID- 27357841 TI - [Potential for the survey of quality indicators based on a national emergency department registry : A systematic literature search]. AB - BACKGROUND: Emergency department processes are often key for successful treatment. Therefore, collection of quality indicators is demanded. A basis for the collection is systematic, electronic documentation. The development of paper based documentation into an electronic and interoperable national emergency registry is-besides the establishment of quality management for emergency departments-a target of the AKTIN project. The objective of this research is identification of internationally applied quality indicators. METHODS: For the investigation of the current status of quality management in emergency departments based on quality indicators, a systematic literature search of the database PubMed, the Cochrane Library and the internet was performed. RESULTS: Of the 170 internationally applied quality indicators, 25 with at least two references are identified. A total of 10 quality indicators are ascertainable by the data set. An enlargement of the data set will enable the collection of seven further quality indicators. The implementation of data of care behind the emergency processes will provide eight additional quality indicators. CONCLUSION: This work was able to show that the potential of a national emergency registry for the establishment of quality indicators corresponds with the international systems taken into consideration and could provide a comparable collection of quality indicators. PMID- 27357842 TI - The channel capacity of visual awareness divided among multiple moving objects. AB - If attention is distributed among multiple moving objects, how does this divided attention affect the temporal process for detecting a specific target motion? Well-trained observers in three experiments monitored ongoing random motions of multiple objects, trying to rapidly detect non-random target motions. Response time hazard rates revealed a simple lawful structure of the detection processes. Target detection rates (hazard rates, in bits /s) were inversely proportional to the number of observed objects. Detection rates at any response time and in any condition equaled a product of two parallel (functionally independent and concurrent) visual processes: visual awareness and motion integration. The rate of visual awareness was inversely proportional to Set Size (n = 1-12), constant over time, and invariant with integrated motion information. Thus, a single rate parameter, indicating a constant channel capacity of visual awareness, described detection rates over a wide range of conditions and response times. During an initial interval of roughly 0.5 s, detection rates increased proportionally with the duration and length of motion; but after this initial integration, detection rates were constant, independent of the time the target remained undetected. The relationship between the quantity of visual information and detection rates was simpler than anticipated by contemporary theories of attention, perception, and performance. PMID- 27357843 TI - The control of attentional target selection in a colour/colour conjunction task. AB - To investigate the time course of attentional object selection processes in visual search tasks where targets are defined by a combination of features from the same dimension, we measured the N2pc component as an electrophysiological marker of attentional object selection during colour/colour conjunction search. In Experiment 1, participants searched for targets defined by a combination of two colours, while ignoring distractor objects that matched only one of these colours. Reliable N2pc components were triggered by targets and also by partially matching distractors, even when these distractors were accompanied by a target in the same display. The target N2pc was initially equal in size to the sum of the two N2pc components to the two different types of partially matching distractors and became superadditive from approximately 250 ms after search display onset. Experiment 2 demonstrated that the superadditivity of the target N2pc was not due to a selective disengagement of attention from task-irrelevant partially matching distractors. These results indicate that attention was initially deployed separately and in parallel to all target-matching colours, before attentional allocation processes became sensitive to the presence of both matching colours within the same object. They suggest that attention can be controlled simultaneously and independently by multiple features from the same dimension and that feature-guided attentional selection processes operate in parallel for different target-matching objects in the visual field. PMID- 27357844 TI - Effects of hypothermically reduced plantar skin inputs on anticipatory and compensatory balance responses. AB - BACKGROUND: Anticipatory and compensatory balance responses are used by the central nervous system (CNS) to preserve balance, hence they significantly contribute to the understanding of physiological mechanisms of postural control. It is well established that various sensory systems contribute to the regulation of balance. However, it is still unclear which role each individual sensory system (e.g. plantar mechanoreceptors) plays in balance regulation. This becomes also evident in various patient populations, for instance in diabetics with reduced plantar sensitivity. To investigate these sensory mechanisms, approaches like hypothermia to deliberately reduce plantar afferent input have been applied. But there are some limitations regarding hypothermic procedures in previous studies: Not only plantar aspects of the feet might be affected and maintaining the hypothermic effect during data collection. Therefore, the aim of the present study was to induce a permanent and controlled plantar hypothermia and to examine its effects on anticipatory and compensatory balance responses. We hypothesized deteriorations in anticipatory and compensatory balance responses as increased center of pressure excursions (COP) and electromyographic activity (EMG) in response to the hypothermic plantar procedure. 52 healthy and young subjects (23.6 +/- 3.0 years) performed balance tests (unexpected perturbations). Subjects' foot soles were exposed to three temperatures while standing upright: 25, 12 and 0 degrees C. COP and EMG were analyzed during two intervals of anticipatory and one interval of compensatory balance responses (intervals 0, 1 and 2, respectively). RESULTS: Similar plantar temperatures confirmed the successful implementation of the thermal platform. No significant COP and EMG differences were found for the anticipatory responses (intervals 0 and 1) under the hyperthermia procedure. Parameters in interval 2 showed generally decreased values in response to cooling. CONCLUSION: No changes in anticipatory responses were found possibly due to sensory compensation processes of other intact afferents. Decreased compensatory responses may be interpreted as the additional balance threat, creating a more cautious behavior causing the CNS to generate a kind of over-compensatory behavior. Contrary to the expectations, there were different anticipatory and compensatory responses after reduced plantar inputs, thereby, revealing alterations in the organization of CNS inputs and outputs according to different task difficulties. PMID- 27357845 TI - Pyrithione-based ruthenium complexes as inhibitors of aldo-keto reductase 1C enzymes and anticancer agents. AB - Four ruthenium complexes of clinically used zinc ionophore pyrithione and its oxygen analog 2-hydroxypyridine N-oxide were prepared and evaluated as inhibitors of enzymes of the aldo-keto reductase subfamily 1C (AKR1C). A kinetic study assisted with docking simulations showed a mixed type of inhibition consisting of a fast reversible and a slow irreversible step in the case of both organometallic compounds 1A and 1B. Both compounds also showed a remarkable selectivity towards AKR1C1 and AKR1C3 which are targets for breast cancer drug design. The organoruthenium complex of ligand pyrithione as well as pyrithione itself also displayed toxicity on the hormone-dependent MCF-7 breast cancer cell line with EC50 values in the low micromolar range. PMID- 27357846 TI - Targeted campaigns must help ethnic minorities spot cancer signs, researchers say. PMID- 27357847 TI - Coherent diffraction imaging: consistency of the assembled three-dimensional distribution. AB - The short pulses of X-ray free-electron lasers can produce diffraction patterns with structural information before radiation damage destroys the particle. From the recorded diffraction patterns the structure of particles or molecules can be determined on the nano- or even atomic scale. In a coherent diffraction imaging experiment thousands of diffraction patterns of identical particles are recorded and assembled into a three-dimensional distribution which is subsequently used to solve the structure of the particle. It is essential to know, but not always obvious, that the assembled three-dimensional reciprocal-space intensity distribution is really consistent with the measured diffraction patterns. This paper shows that, with the use of correlation maps and a single parameter calculated from them, the consistency of the three-dimensional distribution can be reliably validated. PMID- 27357848 TI - Faces of root polytopes in all dimensions. AB - In this paper the root polytopes of all finite reflection groups W with a connected Coxeter-Dynkin diagram in {?bb R}^n are identified, their faces of dimensions 0 <= d <= n - 1 are counted, and the construction of representatives of the appropriate W-conjugacy class is described. The method consists of recursive decoration of the appropriate Coxeter-Dynkin diagram [Champagne et al. (1995). Can. J. Phys. 73, 566-584]. Each recursion step provides the essentials of faces of a specific dimension and specific symmetry. The results can be applied to crystals of any dimension and any symmetry. PMID- 27357849 TI - Properties of X-ray resonant scattering in the Bragg case revealed on the Riemann surface. AB - Continuing the work described in the previous paper [Saka (2016). Acta Cryst. A72, 338-348], the dynamical theory for perfect crystals in the Bragg case is reformulated using the Riemann surface. In particular, diffraction under resonant scattering conditions is investigated. The characteristic features of the dispersion surface and the rocking curve are analytically revealed using four parameters, which are the real and imaginary parts of two quantities specifying the degree of departure from the exact Bragg conditions and the reflection strength. Characteristic properties that have been deduced through numerical analysis are derived analytically using these four parameters. Visualization of the geometric relationships between the four parameters on the Riemann surface is useful for understanding many properties such as symmetry and sharpness of the rocking curve under special conditions. Therefore, employing the Riemann surface is instructive for numerical analysis and useful for understanding dynamical diffraction in the Bragg case. PMID- 27357850 TI - Volumic omit maps in ab initio dual-space phasing. AB - Alternating-projection-type dual-space algorithms have a clear construction, but are susceptible to stagnation and, thus, inefficient for solving the phase problem ab initio. To improve this behaviour new omit maps are introduced, which are real-space perturbations applied periodically during the iteration process. The omit maps are called volumic, because they delete some predetermined subvolume of the unit cell without searching for atomic regions or analysing the electron density in any other way. The basic algorithms of positivity, histogram matching and low-density elimination are tested by their solution statistics. It is concluded that, while all these algorithms based on weak constraints are practically useless in their pure forms, appropriate volumic omit maps can transform them to practically useful methods. In addition, the efficiency of the already useful reflector-type charge-flipping algorithm can be further improved. It is important that these results are obtained by using non-sharpened structure factors and without any weighting scheme or reciprocal-space perturbation. The mathematical background of volumic omit maps and their expected applications are also discussed. PMID- 27357851 TI - Dynamical focusing by bent, asymmetrically cut perfect crystals in Laue geometry. AB - A semi-analytical approach based on the influence functions of a point source located on the crystal surface has been adopted to show that the focusing ability of cylindrically bent Laue crystals may be strongly enhanced by replacing symmetrically cut crystals with asymmetrically cut crystals. This approach is generally applicable to any distance between the X-ray source and the focusing bent crystal. A mathematically straightforward method to simplify the derivation of the already known expression of the influence functions in the case of deformed crystals with a constant strain gradient (e.g. cylindrically bent crystals) is also presented. PMID- 27357852 TI - Frequency analysis for modulation-enhanced powder diffraction. AB - Periodic modulation of external conditions on a crystalline sample with a consequent analysis of periodic diffraction response has been recently proposed as a tool to enhance experimental sensitivity for minor structural changes. Here the intensity distributions for both a linear and nonlinear structural response induced by a symmetric and periodic stimulus are analysed. The analysis is further extended for powder diffraction when an external perturbation changes not only the intensity of Bragg lines but also their positions. The derived results should serve as a basis for a quantitative modelling of modulation-enhanced diffraction data measured in real conditions. PMID- 27357853 TI - Robert Farrell Stewart (1936-2015). PMID- 27357858 TI - Adherence to statin treatment: an important issue in clinical practice. PMID- 27357859 TI - Hollow hydroxyapatite microsphere: a promising carrier for bone tissue engineering. AB - Hydroxyapatite (HA) microsphere with abundant ordered mesoporous and large hollow structure was prepared at hydrothermal condition with the aid of citrate. The obtained microsphere was performed as a drug delivery carrier to evaluate its drug loading/releasing behaviour using alendronate (AL) as a model drug. Results revealed that HA particles performed high AL-loading capability (46.8 wt % with respect to the powdered starting materials) and excellent AL-releasing behaviour (sustained drug releasing profile without burst release). Besides, although a proliferation inhibition phenomenon was observed as HA and AL-loading HA (HA-AL) co-cultured with mesenchymal stem cells (MSCs) at the initial stage, after prolonging co-culture period, compared with HA and control group, HA-AL promoted the cells' proliferation, meanwhile, it facilitated osteogenic differentiation of MSCs and enhanced the expression level of typical markers, all of that ensure HA microsphere is a promising carrier for bone repair. PMID- 27357856 TI - Vitamin D deficiency might pose a greater risk for ApoEE4 non-carrier Alzheimer's disease patients. AB - Vitamin D is a secosteroid hormone that shares a synthetic pathway with cholesterol. ApoE, which is involved in the transport of cholesterol, is the most significant genetic risk factor for sporadic Alzheimer's disease (AD). Surprisingly, recent studies have indicated the presence of an evolutionary juncture between these two molecules. To demonstrate this possible relationship, we investigated serum levels of 25-hydroxyvitamin-D3 (25OHD) in patients with early onset-AD (EOAD; n:22), late onset-AD (LOAD; n:72), mild cognitive impairment (MCI; n:32) and in healthy subjects (n:70). We then analyzed the correlation between 25OHD and cytokines, BDNF and Hsp90 with respect to ApoE alleles, as these molecules were investigated in our previous studies. The LOAD patients had low levels of 25OHD, but these low levels originated only from ApoEE4 non-carrier patients. Negative correlations were observed between serum 25OHD and TNFalpha, IL-1beta or IL-6 levels in healthy subjects or MCI patients, but these same correlations were positive in LOAD patients. ApoE alleles indicated that these positive correlations exist only in E4 carrier LOAD patients. Consequently, our results indicate that vitamin D deficiency presents a greater risk for ApoEE4 non-carrier AD patients than for E4 carriers. Therefore, it might be beneficial to monitor the vitamin D status of ApoEE4 allele non carrier AD patients. PMID- 27357857 TI - Spindle cell embryonal rhabdomyosarcoma of the prostate in an adult patient - case report and review of clinicopathological features. AB - BACKGROUND: Embryonal rhabdomyosarcoma of the prostate in an adult is a very rare event with only a few cases published. Diagnosis usually occurs with advanced disease frequently already with metastatic spread. In adults prognosis is very poor, therefore early diagnosis is crucial. To date, only three cases of spindle cell subtype of embryonal rhabdomyosarcoma of the prostate in an adult have been published. CASE PRESENTATION: We report an additional case of prostatic spindle cell embryonal rhabdomyosarcoma subtype in an adult. CONCLUSIONS: We discuss relevant clinicopathological features of spindle cell embryonal rhabdomyosarcoma of the prostate in adult patients in the context of the literature. PMID- 27357860 TI - Protein stability regulators screening assay (Pro-SRSA): protein degradation meets the CRISPR-Cas9 library. AB - The regulation of protein stability is a fundamental issue for biophysical processes, but there has not previously been a convenient and unbiased method of identifying regulators of protein stability. However, as reported in the article entitled "A genome-scale CRISPR-Cas9 screening method for protein stability reveals novel regulators of Cdc25A," recently published in Cell Discovery, our team developed a protein stability regulators screening assay (Pro-SRSA) by combining the whole-genome clustered regularly interspaced short palindromic repeats Cas9 (CRISPR-Cas9) library with a dual-fluorescence-based protein stability reporter and high-throughput sequencing to screen for regulators of protein stability. Based on our findings, we are confident that this efficient and unbiased screening method at the genome scale will be used by researchers worldwide to identify regulators of protein stability. PMID- 27357861 TI - CrossTalk proposal: Metabolic syndrome causes sleep apnoea. PMID- 27357862 TI - Are Major Depression and Generalized Anxiety Disorder Associated With Oligohydramnios in Pregnant Women? A Case-Control Study. AB - PURPOSE: This study examined the prevalence of major depression and generalized anxiety disorder (GAD) in pregnant women with and without a diagnosis of oligohydramnios. DESIGN AND METHODS: The study sample included 53 pregnant women with a diagnosis of oligohydramnios and 80 healthy pregnant women subjects. Major depression and GAD were diagnosed with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID-I). FINDINGS: Pregnant women with oligohydramnios had higher scores of depressive and anxiety symptom, and a higher prevalence rate of major depression (24.5% vs. 6.2%) and GAD (30.2% vs. 3.2%). PRACTICE IMPLICATIONS: The results of the present study suggest that oligohydramnios appears to be associated with both major depression and GAD in pregnant women. PMID- 27357863 TI - Effect of Gas Pores on Mechanical Properties of High-Pressure Die-Casting AM50 Magnesium Alloy. AB - High-pressure die-casting (HPDC) AM50 tensile specimens were used to investigate characteristics of gas pores and its effect on mechanical properties of HPDC AM50 magnesium alloy. Combining microstructure morphology gained from optical microscopy, scanning electron microscopy (SEM), and three-dimensional (3D) reconstruction with the experimental data from uniaxial tensile testing, we pursued the relationship between gas pores and the mechanical properties of HPDC AM50 Mg alloy. Results indicate that comparing with 3D reconstruction models, 2D images like optical metallography images and SEM images have one-sidedness. Furthermore, the size and maximum areal fraction of gas pores have negative effects on the mechanical properties of HPDC AM50 Mg alloy. With increase of the maximum size of gas pores in the specimen, the ultimate tensile strength (UTS) and elongation decrease. In addition, with the maximum areal fraction becoming larger, both the UTS and elongation decrease linearly. PMID- 27357865 TI - One Step Quantum Key Distribution Based on EPR Entanglement. AB - A novel quantum key distribution protocol is presented, based on entanglement and dense coding and allowing asymptotically secure key distribution. Considering the storage time limit of quantum bits, a grouping quantum key distribution protocol is proposed, which overcomes the vulnerability of first protocol and improves the maneuverability. Moreover, a security analysis is given and a simple type of eavesdropper's attack would introduce at least an error rate of 46.875%. Compared with the "Ping-pong" protocol involving two steps, the proposed protocol does not need to store the qubit and only involves one step. PMID- 27357864 TI - Cortical idiosyncrasies predict the perception of object size. AB - Perception is subjective. Even basic judgments, like those of visual object size, vary substantially between observers and also across the visual field within the same observer. The way in which the visual system determines the size of objects remains unclear, however. We hypothesize that object size is inferred from neuronal population activity in V1 and predict that idiosyncrasies in cortical functional architecture should therefore explain individual differences in size judgments. Here we show results from novel behavioural methods and functional magnetic resonance imaging (fMRI) demonstrating that biases in size perception are correlated with the spatial tuning of neuronal populations in healthy volunteers. To explain this relationship, we formulate a population read-out model that directly links the spatial distribution of V1 representations to our perceptual experience of visual size. Taken together, our results suggest that the individual perception of simple stimuli is warped by idiosyncrasies in visual cortical organization. PMID- 27357866 TI - Successful treatment of bullous pemphigoid with omalizumab as corticosteroid sparing agent: report of two cases and review of literature. AB - BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disease that is characterized by formation of subepidermal bullae due to functional disturbance of the hemidesmosomal proteins on the keratinocytes at the basal membrane zone. In recent years, several studies have emphasized the important role of IgE autoantibodies in the pathogenesis of BP. Consequently, a therapeutic approach using IgE depleting antibodies, such as a humanized monoclonal anti-IgE antibody (e.g. omalizumab) may represent a new option for treatment of this autoimmune disease. METHODS: In this paper, we report about the successful treatment of BP with omalizumab in two patients and provide a review of the current literature on the relationship between IgE antibodies and this autoimmune blistering disease. RESULTS: Two patients with therapy-resistant BP were treated with humanized monoclonal anti-IgE antibody omalizumab 300 mg subcutaneously every 3 weeks as corticosteroid-sparing agent. Under this therapy, both patients experienced a significant improvement of skin condition and almost complete resolution of pruritus. The treatment was well tolerated. CONCLUSION: Until recently IgG autoantibodies against the basal membrane proteins BP180 und BP230 were considered to be causative in the pathogenesis of BP. However, new in vitro studies as well as data from experimental mouse models have indicated that in addition to specific IgG, also IgE antibodies against BP180 and BP230 play a role in the development of this disease. Based on these new findings, new treatment modalities of BP became possible. PMID- 27357900 TI - Developing a Biocascade Process: Concurrent Ketone Reduction-Nitrile Hydrolysis of 2-Oxocycloalkanecarbonitriles. AB - A stereoselective bioreduction of 2-oxocycloalkanecarbonitriles was concurrently coupled to a whole cell-catalyzed nitrile hydrolysis in one-pot. The first step, mediated by ketoreductases, involved a dynamic reductive kinetic resolution, which led to 2-hydroxycycloalkanenitriles in very high enantio- and diastereomeric ratios. Then, the simultaneous exposure to nitrile hydratase and amidase from whole cells of Rhodococcus rhodochrous provided the corresponding 2 hydroxycycloalkanecarboxylic acids with excellent overall yield and optical purity for the all-enzymatic cascade. PMID- 27357867 TI - Outcomes of an extended Morrow procedure without a concomitant mitral valve procedure for hypertrophic obstructive cardiomyopathy. AB - The indications for a concomitant mitral valve (MV) procedure remain controversial for patients with hypertrophic obstructive cardiomyopathy (HOCM). According to previous studies, a concomitant MV surgery was required in 11-20% of inpatient operations. Thus, we aimed to study the outcomes of an extended Morrow procedure without a concomitant MV procedure for HOCM patients who had no intrinsic abnormalities of the MV apparatus. We retrospectively reviewed 232 consecutive HOCM patients who underwent extended Morrow procedures from January 2010 to October 2014. Only 10 (4.31%) patients with intrinsic MV diseases underwent concomitant MV procedures. Of the 232 patients, 230 had no to mild mitral regurgitation (MR) postoperatively. We separated the 232 patients into two groups according to preoperative MR degree. One group is mild MR, and the other is moderate or severe MR. The three-month, one-year, and three-year composite end point event-free survival rates had no difference between two groups (p = 0.820). When we separated the patients to postoperative no or trace MR group and mild MR group, there was also no difference on survival rates (p = 0.830). In conclusion, concomitant mitral valve procedures are not necessary for HOCM patients with MR caused by systolic anterior motion, even moderate to severe extent. PMID- 27357901 TI - SPARCL1-containing neurons in the human brainstem and sensory ganglion. AB - Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is a member of the osteonectin family of proteins. In this study, immunohistochemistry for SPARCL1 was performed to obtain its distribution in the human brainstem, cervical spinal cord, and sensory ganglion. SPARCL1-immunoreactivity was detected in neuronal cell bodies including perikarya and proximal dendrites, and the neuropil. The motor nuclei of the IIIrd, Vth, VIth, VIIth, IXth, Xth, XIth, and XIIth cranial nerves and spinal nerves contained many SPARCL1-immunoreactive (-IR) neurons with medium-sized to large cell bodies. Small and medium-sized SPARCL1-IR neurons were distributed in sensory nuclei of the Vth, VIIth, VIIIth, IXth, and Xth cranial nerves. In the medulla oblongata, the dorsal column nuclei also had small to medium-sized SPARCL1-IR neurons. In addition, SPARCL1-IR neurons were detected in the nucleus of the trapezoid body and pontine nucleus within the pons and the arcuate nucleus in the medulla oblongata. In the cervical spinal cord, the ventral horn contained some SPARCL1-IR neurons with large cell bodies. These findings suggest that SPARCL1-containing neurons function to relay and regulate motor and sensory signals in the human brainstem. In the dorsal root (DRG) and trigeminal ganglia (TG), primary sensory neurons contained SPARCL1 immunoreactivity. The proportion of SPARCL1-IR neurons in the TG (mean +/- SD, 39.9 +/- 2.4%) was higher than in the DRG (30.6 +/- 2.1%). SPARCL1-IR neurons were mostly medium-sized to large (mean +/- SD, 1494.5 +/- 708.3 MUm(2); range, 320.4-4353.4 MUm(2)) in the DRG, whereas such neurons were of various cell body sizes in the TG (mean +/- SD, 1291.2 +/- 532.8 MUm(2); range, 209.3-4326.4 MUm(2)). There appears to be a SPARCL1-containing sensory pathway in the ganglion and brainstem of the spinal and trigeminal nervous systems. PMID- 27357902 TI - An Overview and Future Perspectives of Aluminum Batteries. AB - A critical overview of the latest developments in the aluminum battery technologies is reported. The substitution of lithium with alternative metal anodes characterized by lower cost and higher abundance is nowadays one of the most widely explored paths to reduce the cost of electrochemical storage systems and enable long-term sustainability. Aluminum based secondary batteries could be a viable alternative to the present Li-ion technology because of their high volumetric capacity (8040 mAh cm(-3) for Al vs 2046 mAh cm(-3) for Li). Additionally, the low cost aluminum makes these batteries appealing for large scale electrical energy storage. Here, we describe the evolution of the various aluminum systems, starting from those based on aqueous electrolytes to, in more details, those based on non-aqueous electrolytes. Particular attention has been dedicated to the latest development of electrolytic media characterized by low reactivity towards other cell components. The attention is then focused on electrode materials enabling the reversible aluminum intercalation deintercalation process. Finally, we touch on the topic of high-capacity aluminum sulfur batteries, attempting to forecast their chances to reach the status of practical energy storage systems. PMID- 27357903 TI - Determination of GLUT1 Oligomerization Parameters using Bioluminescent Forster Resonance Energy Transfer. AB - The facilitated glucose transporter GLUT1 (SLC2A1) is an important mediator of glucose homeostasis in humans. Though it is found in most cell types to some extent, the level of GLUT1 expression across different cell types can vary dramatically. Prior studies in erythrocytes-which express particularly high levels of GLUT1-have suggested that GLUT1 is able to form tetrameric complexes with enhanced transport activity. Whether dynamic aggregation of GLUT1 also occurs in cell types with more modest expression of GLUT1, however, is unclear. To address this question, we developed a genetically encoded bioluminescent Forster resonance energy transfer (BRET) assay using the luminescent donor Nanoluciferase and fluorescent acceptor mCherry. By tethering these proteins to the N-terminus of GLUT1 and performing saturation BRET analysis, we were able to demonstrate the formation of multimeric complexes in live cells. Parallel use of flow cytometry and immunoblotting further enabled us to estimate the density of GLUT1 proteins required for spontaneous oligomerization. These data provide new insights into the physiological relevance of GLUT1 multimerization as well as a new variant of BRET assay that is useful for measuring the interactions among other cell membrane proteins in live cells. PMID- 27357904 TI - Polydatin possesses notable anti-osteoporotic activity via regulation of OPG, RANKL and beta-catenin. AB - This study was designed to investigate the anti-osteoporotic activity of polydatin and its possible underlying mechanism. Osteoporosis was induced in mice by ovariectomy (OVX) and the mice were divided into 5 groups: An OVX only group, polydatin groups (10, 20 and 40 mg/kg) and a sham group (n=10/group). After 12 weeks of treatment, body weight, uterine index and the dry weight of thigh-bones were recorded. In addition, the serum calcium, serum phosphorus, alkaline phosphatase (ALP) and osteoprotegerin (OPG) levels were also determined. Western blot analysis was then conducted to investigate the possible mechanism underlying the effect of polydatin via determining the expression of OPG, receptor activators of nuclear factor-kappaB ligand (RANKL) and beta-catenin in the ST2 cell line. The results indicated that intraperitoneal injection of polydatin (10, 20 and 40 mg/kg/day) decreased body weight, and increased uterine index and dry weights of thigh-bones of ovariectomized mice (P<0.05), and polydatin also significantly increased the serum calcium, phosphorus, ALP and OPG of ovariectomized mice (P<0.05). Results of western blot analysis showed that polydatin upregulated the ratio of OPG/RANKL (P<0.05) and beta-catenin protein in ST2 cells. In conclusion, the results demonstrated that polydatin exhibits anti osteoporotic activity via regulating osteoprotegerin, RANKL and beta-catenin. PMID- 27357905 TI - Multiple myocardial crypts: multimodality imaging evaluation. AB - We describe a rare case of multiple myocardial crypts with atypical septal localization, evaluated with multimodality imaging. Although myocardial crypts seem to be more prevalent in hypertensive and hypertrophic cardiomyopathy patients, they are also occasionally found in apparently normal patients. Their clinical significance remains poorly understood. PMID- 27357906 TI - MicroRNA-214 exerts a Cardio-protective effect by inhibition of fibrosis. AB - The miRNAs play important roles in regulating myocardial fibrosis. The purpose of this study was to determine the potential roles of microRNA-214 (miR-214) in cardiac fibrosis in vitro and in vivo. In vitro experiment, Ang II-induced cardiac fibroblasts (CFBs) are transfected with pre-miR-214, anti-miR-214 and their oligo controls. Gene expression was checked by Quantitative realtime-PCR (qRT-PCR) and western blotting. In the present experiment, compared with controls, expressions of collagen type I (COL I), collagen type III (COL III), transforming growth factor (TGF)-beta1, and tissue inhibitors of metalloproteinase (TIMP)-1 were all increased, but matrix metalloproteinase (MMP) 1 was reduced in CFB by Ang II treatment at both mRNA and protein levels, and these alterations were found reversed by miR-214 transfection. In vivo, an anterior transmural acute myocardial infarction (AMI) was created by occlusion of the left anterior descending coronary artery after Ad-pre-miR-214, Ad-anti-miR 214 or Ad-GFP was delivered separately. Four weeks after AMI, protein contents of COL I, COL III and TGF-beta1 in tissue from border area were found increased after AMI, but impaired by overexpression of miR-214. While the expression of MMP 1 was increased by miR-214 stimulation but decreased by miR-214 inhibition. These results suggested that miR-214 exerts cardio-protective effects by inhibition of fibrosis and the inhibitory effect involves TGF-beta1 suppression and MMP-1/TIMP 1 regulation. Anat Rec, 299:1348-1357, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27357908 TI - Obstetric training in Emergency Medicine: a needs assessment. AB - BACKGROUND: Identification and management of obstetric emergencies is essential in emergency medicine (EM), but exposure to pregnant patients during EM residency training is frequently limited. To date, there is little data describing effective ways to teach residents this material. Current guidelines require completion of 2 weeks of obstetrics or 10 vaginal deliveries, but it is unclear whether this instills competency. METHODS: We created a 15-item survey evaluating resident confidence and knowledge related to obstetric emergencies. To assess confidence, we asked residents about their exposure and comfort level regarding obstetric emergencies and eight common presentations and procedures. We assessed knowledge via multiple-choice questions addressing common obstetric presentations, pelvic ultrasound image, and cardiotocography interpretation. The survey was distributed to residency programs utilizing the Council of Emergency Medicine Residency Directors (CORD) listserv. RESULTS: The survey was completed by 212 residents, representing 55 of 204 (27%) programs belonging to CORD and 11.2% of 1,896 eligible residents. Fifty-six percent felt they had adequate exposure to obstetric emergencies. The overall comfort level was 2.99 (1-5 scale) and comfort levels of specific presentations and procedures ranged from 2.58 to 3.97; all increased moderately with postgraduate year (PGY) level. Mean overall percentage of items answered correctly on the multiple-choice questions was 58% with no statistical difference by PGY level. Performance on individual questions did not differ by PGY level. CONCLUSIONS: The identification and management of obstetric emergencies is the cornerstone of EM. We found preliminary evidence of a concerning lack of resident comfort regarding obstetric conditions and knowledge deficits on core obstetrics topics. EM residents may benefit from educational interventions to increase exposure to these topics. PMID- 27357907 TI - Vitamin E succinate induces apoptosis via the PI3K/AKT signaling pathways in EC109 esophageal cancer cells. AB - Esophageal cancer is the fourth most common gastrointestinal cancer, it generally has a poor prognosis and novel strategies are required for prevention and treatment. Vitamin E succinate (VES) is a potential chemical agent for cancer prevention and therapy as it exerts anti-tumor effects in a variety of cancers. However, the role of VES in tumorigenesis and progression of cancer remains to be elucidated. The present study aimed to determine the effects of VES in regulating the survival and apoptosis of human esophageal cancer cells. EC109 human esophageal cancer cells were used to investigate the anti-proliferative effects of VES. The MTT and Annexin V-fluorescein isothiocyanate/propidium iodide assays demonstrated that VES inhibited cell proliferation and induced apoptosis in esophageal cancer cells. Furthermore, VES downregulated constitutively active basal levels of phosphorylated (p)-serine-threonine kinase AKT (AKT) and p mammalian target of rapamycin (mTOR), and decreased the phosphorylation of AKT substrates Bcl-2-associated death receptor and caspase-9, in addition to mTOR effectors, ribosomal protein S6 kinase beta1 and eIF4E-binding protein 1. Phosphoinositide-3-kinase (PI3K) inhibitor, LY294002 suppressed p-AKT and p-mTOR, indicating PI3K is a common upstream mediator. The apoptosis induced by VES was increased by inhibition of AKT or mTOR with their respective inhibitor in esophageal cancer cells. The results of the present study suggested that VES targeted the PI3K/AKT signaling pathways and induced apoptosis in esophageal cancer cells. Furthermore, the current study suggests that VES may be useful in a combinational therapeutic strategy employing an mTOR inhibitor. PMID- 27357909 TI - The effect of Mind Body Medicine course on medical student empathy: a pilot study. AB - INTRODUCTION: Empathy among medical practitioners has been shown to affect patient care and outcomes. Factors such as stress and depression are known to have a negative impact on medical student empathy. Approaches such as mindfulness, meditation, and other mind-body techniques can enhance empathy and reverse burnout symptoms. In the present study, we evaluated impact of Mind Body Medicine (MBM) course on perceived stress and empathy on first-year medical students. METHODS: Thirteen first-year medical students in total self-selected into MBM (experimental) and seven non-MBM (control) groups completed a prospective, pre- and post-test analysis, using the Jefferson Scale of Physician Empathy - Students (JSPE-S), Perceived Stress Scale (PSS), and Personal Health Questionnaire (PHQ) to evaluate empathy, stress, and depression, respectively. RESULTS: Our results showed an increase in stress, as well as a decrease in empathy, in both MBM and non-MBM groups throughout the course of the study. CONCLUSION: Our study demonstrated that the inverse relationship increased stress and decreased empathy among first-year medical students and participation in the MBM course did not attenuate the changes. However, a statistically significant rise in the depression score in the non-MBM group was not observed in the MBM group. PMID- 27357910 TI - Faculty attitudes about interprofessional education. AB - BACKGROUND: Interprofessional education (IPE) is an important component to training health care professionals. Research is limited in exploring the attitudes that faculty hold regarding IPE and what barriers they perceive to participating in IPE. The purpose of this study was to identify faculty attitudes about IPE and to identify barriers to participating in campus-wide IPE activities. METHODS: A locally used questionnaire called the Nebraska Interprofessional Education Attitudes Scale (NIPEAS) was used to assess attitudes related to interprofessional collaboration. Questions regarding perceived barriers were included at the end of the questionnaire. Descriptive and non parametric statistics were used to analyze the results in aggregate as well as by college. In addition, open-ended questions were analyzed using an immersion/crystallization framework to identify themes. RESULTS: The results showed that faculty had positive attitudes of IPE, indicating that is not a barrier to participating in IPE activities. Most common barriers to participation were scheduling conflicts (x24,285=19.17, p=0.001), lack of department support (x24,285=10.09, p=0.039), and lack of awareness of events (x24,285=26.38, p=0.000). Narrative comments corroborated that scheduling conflicts are an issue because of other priorities. Those who commented also added to the list of barriers, including relevance of the activities, location, and prior negative experiences. DISCUSSION: With faculty attitudes being positive, the exploration of faculty's perceived barriers to IPE was considered even more important. Identifying these barriers will allow us to modify our IPE activities from large, campus-wide events to smaller activities that are longitudinal in nature, embedded within current curriculum and involving more authentic experiences. PMID- 27357911 TI - RLS3, a protein with AAA+ domain localized in chloroplast, sustains leaf longevity in rice. AB - Leaf senescence plays an important role in crop developmental processes that dramatically affect crop yield and grain quality. The genetic regulation of leaf senescence is complex, involving many metabolic and signaling pathways. Here, we identified a rapid leaf senescence 3 (rls3) mutant that displayed accelerated leaf senescence, shorter plant height and panicle length, and lower seed set rate than the wild type. Map-based cloning revealed that RLS3 encodes a protein with AAA+ domain, localizing it to chloroplasts. Sequence analysis found that the rls3 gene had a single-nucleotide substitution (G->A) at the splice site of the 10th intron/11th exon, resulting in the cleavage of the first nucleotide in 11th exon and premature termination of RLS3 protein translation. Using transmission electron microscope, the chloroplasts of the rls3 mutant were observed to degrade much faster than those of the wild type. The investigation of the leaf senescence process under dark incubation conditions further revealed that the rls3 mutant displayed rapid leaf senescence. Thus, the RLS3 gene plays key roles in sustaining the normal growth of rice, while loss of function in RLS3 leads to rapid leaf senescence. The identification of RLS3 will be helpful to elucidate the mechanisms involved in leaf senescence in rice. PMID- 27357912 TI - Splenic infarction associated with acute infectious mononucleosis due to Epstein Barr virus infection. AB - The purpose of this study was to report a case of a previously healthy 20-year old woman diagnosed with splenic infarction following infectious mononucleosis (IM) by Epstein-Barr virus (EBV) infection and to perform the first systematic review of the clinical characteristics of splenic infarction associated with IM. A systematic review was conducted using English, French, and Japanese literatures of splenic infarction associated with IM due to EBV infection published between 1961 and 2015 in PubMed Medline. A total of 19 cases were extracted from the collected articles. Left upper quadrant (LUQ) pain was observed in 15 (79%) patients. Splenectomy was performed in five (26%) cases, among which four patients presented with stable vital signs. Splenic rupture was accompanied in two (10%) patients. The median time from the onset of IM symptoms to the diagnosis of splenic infarction was 5 days (range, 1-25 days). Fourteen (74%) of 19 patients experienced improvement through medical treatment, and there were no deaths. Splenic infarction associated with IM due to EBV infection can show a favorable clinical outcome after medical treatment. Clinicians should consider the possibility of splenic infarction when patients with IM experience LUQ pain. J. Med. Virol. 89:332-336, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27357913 TI - Leaf Metabolic, Genetic, and Morphophysiological Profiles of Cultivated and Wild Rocket Salad (Eruca and Diplotaxis Spp.). AB - Rocket salad (Diplotaxis spp., Eruca spp.) is a leafy vegetable rich in health promoting compounds and widely consumed. In the present study, metabolic profiles of 40 rocket accessions mainly retrieved from gene banks were assessed. Seven glucosinolates (GLSs) and 15 flavonol compounds were detected across genotypes. Dimeric 4-mercaptobutyl-GLS and 4-(beta-d-glucopyranosyldisulfanyl)butyl-GLS were the major components of the total glucosinolate content. Flavonols were different between genera, with the exception of isorhamnetin 3,4'-diglucoside. Morphoagronomic traits and color coordinates were also scored. Results showed a negative correlation between color and GLSs, indicating these last as responsible for the increase of the intensity of green and yellow pigments as well as for the darkness of the leaf, whereas agronomic traits showed positive correlation with GLSs. Genetic diversity was assessed using inter simple sequence repeat (ISSR) markers, allowing separation of the accessions on the basis of the species and elucidating the observations made by means of phenotypic data. PMID- 27357914 TI - Haemostatic biomarkers are associated with long-term recurrent vascular events after ischaemic stroke. AB - Ischaemic stroke patients continue to be at risk for recurrent vascular events for many years. Predictors of long-term prognosis are needed. It was the objective of this study to investigate levels of four haemostatic proteins as long-term predictors of recurrent vascular events after ischaemic stroke. We prospectively followed 548 ischaemic stroke patients, 18-69 years, and registered recurrent vascular events. Plasma levels of tissue-type plasminogen activator (t PA), von Willebrand factor (VWF), fibrinogen and thrombin activatable fibrinolysis inhibitor activation peptide (TAFI-AP) were measured three months after index stroke. Cox regression models were used to assess associations to outcomes for single biomarkers and for a combined biomarker measure. For single biomarkers significantly associated with any of the outcomes, we performed subanalyses stratified for age, sex, diabetes and atherosclerosis. During 5,637 person-years of follow-up, we registered 74 vascular deaths, 90 recurrent strokes and 62 coronary events. Levels of t-PA, VWF and fibrinogen were significantly associated with vascular death and coronary events. After adjustment, the association between t-PA and vascular death remained (HR per 1 SD increase in plasma level 1.27, 95 % CI 1.00-1.61, p=0.047). The combined effect of t-PA, VWF and fibrinogen was associated with coronary events (adjusted HR 1.35, 1.02-1.80, p=0.04). In non-diabetic patients, an association with coronary events was seen for VWF levels (adjusted HR 2.23, 1.45-3.43, p<0.01). In conclusion, plasma levels of haemostatic factors were associated with vascular death and coronary events, but not with recurrent stroke. Our results suggest that the predictive value of biomarkers differ by specific outcome measure and subgroup of patients. PMID- 27357915 TI - Bioaccumulation of organochlorine pesticides (OCPs) in the northern fulmar (Fulmarus glacialis) from the Sea of Okhotsk. AB - Hexachlorocyclohexane (HCH) isomers (alpha-, beta-, and gamma-), DDT and its metabolites (DDD and DDE) were detected in five individuals of Northern fulmar Fulmarus glacialis Linnaeus, 1761 from the Sea of Okhotsk. The average amount of HCHs in the organs of fulmars ranged from 608+/-177ng/g lipids in the total homogenate of the organs to 2093+/-264ng/g lipids in the feathers with skin. The average range of the amounts of DDTs was from 3606+/-333ng/g lipids in the feathers with skin to 4076+/-1624ng/g lipids in the feathers. The bioaccumulation of DDTs by seabirds of the Sea of Okhotsk is approximately equal to that of birds from other regions of the world's oceans, while the HCHs concentration is significantly higher. PMID- 27357916 TI - Comparative bioavailability of ammonium, nitrate, nitrite and urea to typically harmful cyanobacterium Microcystis aeruginosa. AB - Phosphorus is generally considered as the prime limiting nutrient responsible for cyanobacterial blooms. However, recent research is drawing attention to the importance of bioavailable nitrogen (N) in freshwater eutrophication. This study investigated the bioavailability of NO3(-)-N, NO2(-)-N, NH4(+)-N and Urea-N under different concentrations of 1.2, 3.6 and 6.0mgL(-1) to Microcystis aeruginosa. Overall, Urea-N ranked the first in promoting M. aeruginosa growth, followed by NO3(-)-N and NO2(-)-N. However, the algal growth cultured in NH4(+)-N was depressed under test N levels. The bioavailability of N to M. aeruginosa was seriously influenced by both N forms and N concentrations (p<0.01). Total N concentrations in Urea-N treatment decreased the fastest, which were corresponding with the MU values of M. aeruginosa. The high enzymic activities of nitrate reductase, nitrite reductase and glutamine synthetase indicated that the decomposition process for urea is effective, which contributed in N assimilation and utilization in M. aeruginosa cells. PMID- 27357917 TI - Assessing pollution-related effects of oil spills from ships in the Chinese Bohai Sea. AB - An analysis of the effects of potential oil spills will provide data in support of decisions related to improving the response to oil spills and its emergency management. We selected the Chinese Bohai Sea, especially the Bohai Strait, as our investigation region to provide an assessment of the effects of pollution from ship-related oil spills on adjacent coastal zones. Ship-related accidents are one of the major factors causing potential oil spills in this area. A three dimensional oil transport and transformation model was developed using the Estuary, Coastal, and Ocean Model. This proposed model was run 90 times and each run lasted for 15days to simulate the spread and weathering processes of oil for each of four potential spill sites, which represented potential sites of ship collisions along heavy traffic lanes in the Bohai Sea. Ten neighboring coastal areas were also considered as target zones that potentially could receive pollutants once oil spilled in the study areas. The statistical simulations showed that spills in winter were much worse than those in summer; they resulted in very negative effects on several specific target zones coded Z7, Z8, Z9, and Z10 in this paper. In addition, sites S3 (near the Penglai city) and S4 (near the Yantai city) were the two most at-risk sites with a significantly high probability of pollution if spills occurred nearby during winter. The results thus provided practical guidelines for local oil spill prevention, as well as an emergency preparedness and response program. PMID- 27357919 TI - The Pilates method and cardiorespiratory adaptation to training. AB - Although all authors report beneficial health changes following training based on the Pilates method, no explicit analysis has been performed of its cardiorespiratory effects. The objective of this study was to evaluate possible changes in cardiorespiratory parameters with the Pilates method. A total of 45 university students aged 18-35 years (77.8% female and 22.2% male), who did not routinely practice physical exercise or sports, volunteered for the study and signed informed consent. The Pilates training was conducted over 10 weeks, with three 1-hour sessions per week. Physiological cardiorespiratory responses were assessed using a MasterScreen CPX apparatus. After the 10-week training, statistically significant improvements were observed in mean heart rate (135.4 124.2 beats/min), respiratory exchange ratio (1.1-0.9) and oxygen equivalent (30.7-27.6) values, among other spirometric parameters, in submaximal aerobic testing. These findings indicate that practice of the Pilates method has a positive influence on cardiorespiratory parameters in healthy adults who do not routinely practice physical exercise activities. PMID- 27357918 TI - A clinically authentic mouse model of enterovirus 71 (EV-A71)-induced neurogenic pulmonary oedema. AB - Enterovirus 71 (EV-A71) is a neurotropic virus that sporadically causes fatal neurologic illness among infected children. Animal models of EV-A71 infection exist, but they do not recapitulate in animals the spectrum of disease and pathology observed in fatal human cases. Specifically, neurogenic pulmonary oedema (NPE)-the main cause of EV-A71 infection-related mortality-is not observed in any of these models. This limits their utility in understanding viral pathogenesis of neurologic infections. We report the development of a mouse model of EV-A71 infection displaying NPE in severely affected animals. We inoculated one-week-old BALB/c mice with an adapted EV-A71 strain and identified clinical signs consistent with observations in human cases and other animal models. We also observed respiratory distress in some mice. At necropsy, we found their lungs to be heavier and incompletely collapsed compared to other mice. Serum levels of catecholamines and histopathology of lung and brain tissues of these mice strongly indicated onset of NPE. The localization of virally-induced brain lesions also suggested a potential pathogenic mechanism for EV-A71-induced NPE. This novel mouse model of virally-induced NPE represents a valuable resource for studying viral mechanisms of neuro-pathogenesis and pre-clinical testing of potential therapeutics and prophylactics against EV-A71-related neurologic complications. PMID- 27357920 TI - Frozen Elephant Trunk Technique in a Patient with Multiple Previous Cardiac Procedures: A Case Report. AB - BACKGROUND We present the case of a 69-year-old female patient with giant aortic aneurysm who underwent previously multiple cardiac surgeries or interventions. CASE REPORT Ross procedure was performed in 2006 due to aortic valve regurgitation and aneurysm of the ascending aorta. In 2010 the patient was re admitted for pulmonary valve insufficiency and a transcatheter pulmonary valve was implanted. Recently, the patient presented with an aortic arch aneurysm, maximum diameter 78 mm, which was treated by a hybrid approach, implanting a frozen elephant trunk and a covered stent graft. CONCLUSIONS The current case report demonstrates a suitable hybrid option for an extremely demanding procedure by multiple previous cardiac procedures. PMID- 27357921 TI - Attempting to be active: Self-efficacy and barrier limitation differentiate activity levels of working mothers. AB - Working mothers are less physically active than working women without children and mothers who do not work. The purpose of this study was to examine concurrent self-regulatory efficacy and barriers to physical activity in a sample of working mothers. Women completed a mixed-methods survey which included measures of physical activity, concurrent self-regulatory efficacy, and barriers. Sufficiently active women experienced significantly greater concurrent self regulatory efficacy and significantly less barrier limitation and frequency. No significant group differences were found for age, domestic duties performed, and children's extracurricular activities. Thematic analysis of barriers revealed six themes of common and unique factors, including limited time and family activities. PMID- 27357922 TI - Does parent's psychological distress mediate the relationship between war trauma and psychosocial adjustment in children? AB - This study investigated the impact of war trauma on behavioral and emotional disorders, and neuroticism in children by prospectively examining the potential mediator and/or moderator effects of parental psychological distress. The sample consisted of 205 parents and their children. The results indicated that parent's psychological distress did mediate and moderate the effect of trauma exposure on emotional and behavioral disorders in children. An integrated intervention which simultaneously targets children and parental distress symptoms is needed. The integrated intervention may intend to use trauma-focused cognitive behavioral therapy model that integrates cognitive, behavioral, interpersonal, and family therapy principles with trauma interventions. PMID- 27357923 TI - When the treatment stops: A qualitative study of life post breast cancer treatment. AB - Public attention focuses on breast cancer treatment and fundraising; however, there is limited discussion about life post-treatment. Once treatment is complete, there can be societal expectations of newfound wellness. To understand this phenomenon, the narratives of nine women post-treatment were explored. Analysis revealed the adoption of the sick role by the participants, the vulnerability experienced with the cessation of treatment, the disturbance of moving on from the security of the medical system and the patient and doctor relationship. Findings emphasised that survivorship can remain challenging and can present adverse psychosocial implications for women and those close to them. PMID- 27357924 TI - The Chinese Mental Resilience Scale and its psychometric properties. AB - This study aimed to develop a Chinese Mental Resilience Scale. A total of 2500 healthy participants, in two representative samples of the Chinese population, were administered the scale. Exploratory factor analysis, confirmatory factor analysis, and correlation analysis were used to obtain the relevant coefficients and verify the reliability and validity of the scale. Five factors were extracted: willpower, family support, optimism and self-confidence, problem solving, and interpersonal interaction, plus a lying subscale, which together accounted for 54 percent of the total variance. The Chinese Mental Resilience Scale demonstrated good psychometric properties. It can be used to evaluate the mental resilience level of general Chinese population. PMID- 27357925 TI - Oral microbiome diversity among Cheyenne and Arapaho individuals from Oklahoma. AB - OBJECTIVES: There is a major ascertainment bias in microbiome research, with individuals of predominately European ancestry living within metropolitan areas dominating most studies. Here we present a study of the salivary microbiome within a North American Indian community. This research is the culmination of four years of collaboration and community engagement with Cheyenne & Arapaho (C&A) tribal members from western Oklahoma. MATERIALS AND METHODS: Using 16S rRNA gene amplification and next-generation sequencing, we generated microbial taxonomic inventories for 37 individuals representing five towns within the C&A tribes. For comparison, we performed the same laboratory techniques on saliva samples from 20 non-native individuals (NNI) from Norman, Oklahoma. RESULTS: The C&A participants differ from the NNI in having reduced within-individual species richness and higher between-individual variation. Unsupervised clustering analyses reveal that three ecological groupings best fit the data, and while C&A individuals include assignments to all three groups, the NNI individuals are assigned to only one group. One of the ecological groups found exclusively among C&A participants was characterized by high abundance of the oral bacterial genus Prevotella. DISCUSSION: The C&A and NNI participants from Oklahoma have notable differences in their microbiome diversity, with a wider range of variation observed among the C&A individuals, including a higher frequency of bacteria implicated in systemic disorders. Overall, this study highlights the importance of engagement with indigenous communities, and the need for an improved understanding of human microbiome diversity among underrepresented groups and those individuals living outside of metropolitan areas. PMID- 27357926 TI - Treatment of routine adolescent inguinal hernia vastly differs between pediatric surgeons and general surgeons. AB - BACKGROUND: Surgical treatment of inguinal hernias in adolescents is controversial as these patients do not fit into the traditional pediatric and adult populations. We aimed to compare the preferences of adult general surgeons and pediatric surgeons in managing adolescents by conducting a survey through social media. METHODS: A poll was posted on the International Hernia Collaboration Group Facebook page as well as the Facebook page for the authoring pediatric surgeon. The poll gave scenarios of a 16-year-old male with an inguinal hernia and asked surgeons to select one of five listed procedures to repair the hernia: high ligation (open or laparoscopic), mesh repair (open or laparoscopic) or open muscle repair. The four scenarios differed in the diameter of the internal ring (1 vs. 4 cm) and the BMI of the patient (20 vs. 35). Fisher's exact test was implemented for statistical analysis. RESULTS: In total, 43 (67 %) adult surgeons and 21 (33 %) pediatric surgeons responded. In the routine adolescent (normal BMI, small defect), 65 % of adult surgeons chose adult-type repairs (mesh or muscle repairs) whereas 86 % of pediatric surgeons chose pediatric-type repairs (high ligation). When the size of the defect increased, 100 % of adult surgeons and 81 % of pediatric surgeons selected an adult-type repair, suggesting agreement. When the patient was obese, there was a tendency to prefer laparoscopy. In all patient scenarios, the answers were significantly different between pediatric and adult surgeons (p < 0.05). CONCLUSION: For the same routine adolescent inguinal hernia, pediatric surgeons and adult general surgeons choose a different procedure. This finding suggests that further study is needed to determine the optimal treatment for inguinal hernias in adolescents, as the type of practitioner to whom the patient is referred, rather than the disease process itself, currently dictates treatment. PMID- 27357927 TI - Management of patients with T1b esophageal adenocarcinoma: a retrospective cohort study on patient management and risk of metastatic disease. AB - BACKGROUND: Esophagectomy for submucosal (T1b) esophageal adenocarcinoma (EAC) is performed in order to optimize patient outcomes given the risk of concurrent lymph node metastases (LNM). However, not seldom, comorbidity precludes these patients from surgery. Therefore, the aim of our study was to assess the course of follow-up after treatment in submucosal EAC patients undergoing surgery versus conservative therapy and to evaluate the incidence of metastatic disease. METHODS: Between 2001 and 2012, all patients undergoing diagnostic endoscopic resection for EAC in two centers were reviewed. Only patients with histopathologically proven submucosal tumor invasion were included. Submucosal EACs were divided into tumors that were removed radically (R0) and irradically (R1). Subsequently, in the R0 group, EACs were classified as either low risk (LR; submucosal invasion <500 nm, G1-G2, no LVI) or high risk (HR; deep submucosal invasion >500 nm, G3-G4 and/or LVI). Metastatic disease was defined as LNM in surgical resection specimen and/or evidence of malignant disease during follow-up (FU). RESULTS: Sixty-nine patients with a submucosal EAC were included [23 R1 resections and 46 R0-resection (14 R0-LR and 32 R0-HR)]. Twenty-six patients underwent surgical treatment (1 R0-LR, 12 R0-HR and 13 R1). None of the 14 R0-LR patients developed metastatic disease after a median FU of 60 months. In the R0 HR group and R1 group, metastatic disease was diagnosed in 16 and 30 % of patients, respectively. Surgical patients tended to have a better overall survival than non-surgical patients (p = 0.09). Tumor-related deaths, however, were 12 % in both groups. CONCLUSIONS: In LR submucosal EAC, the risk of metastatic disease appears to be very low. In deep submucosal EAC (either R0- or R1-resection), the rate of metastatic disease is lower than reported in earlier surgical series. Given the reasonable disease-free survival and high background mortality, conservative management of these patients seems to be a valid alternative for surgery in selected cases. PMID- 27357928 TI - Laparoscopic detection and resection of occult liver tumors of multiple cancer types using real-time near-infrared fluorescence guidance. AB - BACKGROUND: Tumor recurrence after radical resection of hepatic tumors is not uncommon, suggesting that malignant lesions are missed during surgery. Intraoperative navigation using fluorescence guidance is an innovative technique enabling real-time identification of (sub)capsular liver tumors. The objective of the current study was to compare fluorescence imaging (FI) and conventional imaging modalities for laparoscopic detection of both primary and metastatic tumors in the liver. METHODS: Patients undergoing laparoscopic resection of a malignant hepatic tumor were eligible for inclusion. Patients received standard of care, including preoperative CT and/or MRI. In addition, 10 mg indocyanine green was intravenously administered 1 day prior to surgery. After introduction of the laparoscope, inspection, FI, and laparoscopic ultrasonography (LUS) were performed. Histopathological examination of resected suspect tissue was considered the gold standard. RESULTS: Twenty-two patients suspected of having hepatocellular carcinoma (n = 4), cholangiocarcinoma (n = 2) or liver metastases from colorectal carcinoma (n = 12), uveal melanoma (n = 2), and breast cancer (n = 2) were included. Two patients were excluded because their surgery was unexpectedly postponed several days. Twenty-six malignancies were resected in the remaining 20 patients. Sensitivity for various modalities was 80 % (CT), 84 % (MRI), 62 % (inspection), 86 % (LUS), and 92 % (FI), respectively. Three metastases (12 %) were identified solely by FI. All 26 malignancies could be detected by combining LUS and FI (100 % sensitivity). CONCLUSION: This study demonstrates added value of FI during laparoscopic resections of several hepatic tumors. Although larger series will be needed to confirm long-term patient outcome, the technology already aids the surgeon by providing real-time fluorescence guidance. PMID- 27357929 TI - Retention of laparoscopic skills in naive medical students who underwent short training. AB - BACKGROUND: Simulators are useful tools in the development of laparoscopic skills. However, little is known about the effectiveness of short laparoscopic training sessions and how retention of skills occurs in surgical trainees who are naive to laparoscopy. This study analyses the retention of laparoscopic surgical skills in medical students without prior surgical training. METHODS: A group of first- and second-year medical students (n = 68), without prior experience in surgery or laparoscopy, answered a demographic questionnaire and had their laparoscopic skills assessed by the Fundamentals of Laparoscopic Surgery (FLS) training protocol. Subsequently, they underwent a 150-minute training course after which they were re-tested. One year after the training, the medical students' performance in the simulator was re-evaluated in order to analyse retention. RESULTS: Of the initial 68 students, a total of 36 participated throughout the entire study, giving a final participation rate of 52 %. Thirty six medical students with no gender predominance and an average age of 20 years were evaluated. One year after the short training programme, retention was 69.3 % in the peg transfer (p < 0.05) and 64.2 % in ligature (p < 0.05) compared with immediate post-training evaluation. There was no significant difference in suturing. The average sample score in the baseline test was 8.3, in the post training test it was 89.7, and in the retention test it was 84.2, which corresponded to a skill retention equivalence of 93 %. CONCLUSIONS: There was a significant retention of the laparoscopic surgical skills developed. Even 1 year after a short training session, medical students without previous surgical experience showed that they have retained a great part of the skills acquired through training. PMID- 27357931 TI - Adipocytes, aldosterone and obesity-related hypertension. AB - Understanding the mechanisms linking obesity with hypertension is important in the current obesity epidemic as it may improve therapeutic interventions. Plasma aldosterone levels are positively correlated with body mass index and weight loss in obese patients is reported to be accompanied by decreased aldosterone levels. This suggests a relationship between adipose tissue and the production/secretion of aldosterone. Aldosterone is synthesized principally by the adrenal glands, but its production may be regulated by many factors, including factors secreted by adipocytes. In addition, studies have reported local synthesis of aldosterone in extra-adrenal tissues, including adipose tissue. Experimental studies have highlighted a role for adipocyte-secreted aldosterone in the pathogenesis of obesity-related cardiovascular complications via the mineralocorticoid receptor. This review focuses on how aldosterone secretion may be influenced by adipose tissue and the importance of these mechanisms in the context of obesity-related hypertension. PMID- 27357932 TI - A prospective study of angiogenic markers and postmenopausal breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. AB - PURPOSE: Pro-angiogenic factors are positively associated with breast tumor staging and poorer prognosis, but their role in the etiology of breast cancer has not been assessed. METHODS: We measured serum levels of the pro-angiogenic vascular endothelial growth factor A (VEGF), and placental growth factor (PlGF) and anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) in 352 incident breast cancer cases [mean age at diagnosis 67 (range 55-83)] and 352 non-cases in the prostate, lung, colorectal, and ovarian screening trial (women enrolled 1993 2001, followed through 2005) matched on age and date of enrollment. Cases were followed on average 4.2 years from blood draw to diagnosis, range 3.9-12.8 years; 53 % were estrogen receptor positive/progesterone receptor positive (ER+/PR+), and 13 % were ER-/PR-. Quartile-specific hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using weighted Cox proportional hazards regression models adjusted for known breast cancer risk factors. An ordinal variable for the angiogenic markers was used to test for trend in the HR. RESULTS: Comparing the highest to lowest quartile, multivariable HR were 0.90 for VEGF (95 % CI 0.33 2.43, p trend = 0.88), 1.38 for sFlt-1 (95 % CI 0.63-3.04, p trend = 0.63), and 0.62 for PlGF (95 % CI 0.19-2.00, p trend = 0.73). Risk patterns were not altered when all angiogenic markers were included in the model simultaneously, or by restricting analyses to invasive breast cancers, to cases diagnosed two or more years after blood collection or to ER+ tumors. CONCLUSIONS: There was no evidence of an increased breast cancer risk associated with circulating levels of pro angiogenic markers VEGF and PlGF or a reduced risk with circulating levels of anti-angiogenic marker sFlt-1. PMID- 27357934 TI - Corrigendum. AB - Massey CJ, Suh JD, Tessema B, Gray ST, Singh A. Biomaterials in rhinology. Otolaryngol Head Neck Surg 2016;154:606-617. (Original DOI: 10.1177/0194599815627782). PMID- 27357933 TI - Impaired Gastrointestinal Function Affects Symptoms and Alimentary Status in Patients After Gastrectomy. AB - BACKGROUND: Postgastrectomy syndrome (PGS) remains a common complication after gastrectomy that affects patients' quality of life. Although impaired gastrointestinal (GI) function by gastrectomy procedures is thought to be the cause, the precise pathophysiology of PGS is yet to be clarified. AIM: The aim of this study was to investigate relationships between GI function and various symptoms or alimentary status in patients after gastrectomy. METHODS: Fifty-one patients who underwent total or distal gastrectomy at least 1 year previously were studied. All patients replied to a questionnaire that asked presence of symptoms (esophageal reflux, nausea, abdominal pain, early satiation, diarrhea, early dumping general, early dumping abdominal, and late dumping symptoms) and alimentary status (change in body weight, food intake per meal, frequency of meals per day). They also underwent assessment of GI function consisting of gastric emptying study by 13C-acetate breath test to examine reservoir capacity and gastric emptying, and water load drink test to evaluate tolerance to volume loading (TVL). The relationships between GI function and each symptom or alimentary status were examined. RESULTS: The patients with nausea and early dumping general symptoms had significantly smaller reservoir capacity*, the patients with diarrhea and early dumping general symptoms had significantly faster gastric emptying*, and the patients with early satiation and early dumping abdominal symptoms had significantly impaired TVL*. Significant correlations were identified between TVL and body weight changes* or food intake per meal* (* p < 0.05). CONCLUSION: Impaired postoperative GI function was closely related to symptoms or worse alimentary status. PMID- 27357935 TI - Paying more attention to the 'elephant in the room'. AB - This commentary argues that a nicotine reduction strategy for tobacco control is a secondary strategy to the wider availability of low toxin forms of nicotine to give smokers a viable alternative to cigarettes. Failure to confront the likely reality of continued nicotine use and to make it as low in harm as possible may prolong the tobacco epidemic. PMID- 27357936 TI - What is included with your online e-cigarette order? An analysis of e-cigarette shipping, product and packaging features. AB - BACKGROUND: The electronic cigarette industry is growing, with youth using e cigarettes at higher rates than they are using cigarettes, and retail and online sales projected to reach $10 billion in 2017. Minimal regulation of the production and marketing of e-cigarettes exists to date, which has allowed companies to promote unsupported claims. We assessed the shipping, product features and packaging of a wide variety of e-cigarettes purchased online by adults and youth. METHODS: The most popular internet e-cigarette vendors were identified from a larger study of internet tobacco vendors. Between August 2013 and June 2014, adults made 56 purchase attempts from online vendors, and youth made 98 attempts. Packages received were assessed for exterior and internal packaging features, including product information, health warnings and additional materials. RESULTS: We analysed a total of 125 orders featuring 86 unique brands of e-cigarettes. The contents were rarely indicated on package exteriors. Product information came with just 60% of orders and just 38.4% included an instruction manual. Only 44.6% of products included a health warning, and some had unsupported claims, such as lack of secondhand smoke exposure. Additionally, some products were leaking e-liquid and battery fluid on arrival. CONCLUSIONS: A large variety of e-cigarette products are manufactured and marketed to consumers. Many products do not include instructions for use, and unsupported claims are being presented to consumers. Effective federal regulation of the manufacturing, packaging, product information and health claims surrounding e-cigarettes is necessary to ensure consumers are presented with accurate e-cigarette use information. PMID- 27357937 TI - Cigarette prohibition and the need for more prior testing of the WHO TobReg's global nicotine-reduction strategy. PMID- 27357938 TI - The case for the WHO Advisory Note, Global Nicotine Reduction Strategy. PMID- 27357939 TI - Middle Iron-Enriched Fructose Diet on Gestational Diabetes Risk and on Oxidative Stress in Offspring Rats. AB - Gestational diabetes mellitus (GDM) is associated with increased insulin resistance and a heightened level of oxidative stress (OS). Additionally, high iron consumption could also increase insulin resistance and OS, which could aggravate GDM risk. The aim of this study is to evaluate a high fructose diet (F) as an alternative experimental model of GDM on rats. We also have evaluated the worst effect of a fructose iron-enriched diet (FI) on glucose tolerance and OS status during pregnancy. Anthropometric parameters, plasma glucose levels, insulin, and lipid profile were assessed after delivery in rats fed an F diet. The effects observed in mothers (hyperglycemia, and hyperlipidemia) and on pups (macrosomia and hypoglycemia) are similar to those observed in women with GDM. Therefore, the fructose diet could be proposed as an experimental model of GDM. In this way, we can compare the effect of an iron-enriched diet on the metabolic and redox status of mother rats and their pups. The mothers' glycemic was similar in the F and FI groups, whereas the glycemic was significantly different in the newborn. In rat pups born to mothers fed on an FI diet, the activities of the antioxidant enzyme glutathione peroxidase (GPx) and glutathione-S-transferase in livers and GPx in brains were altered and the gender analysis showed significant differences. Thus, alterations in the glycemic and redox status in newborns suggest that fetuses are more sensitive than their mothers to the effect of an iron-enriched diet in the case of GDM pregnancy. This study proposed a novel experimental model for GDM and provided insights on the effect of a moderate iron intake in adding to the risk of glucose disorder and oxidative damage on newborns. PMID- 27357941 TI - Methylmercury, an environmental electrophile capable of activation and disruption of the Akt/CREB/Bcl-2 signal transduction pathway in SH-SY5Y cells. AB - Methylmercury (MeHg) modifies cellular proteins via their thiol groups in a process referred to as "S-mercuration", potentially resulting in modulation of the cellular signal transduction pathway. We examined whether low-dose MeHg could affect Akt signaling involved in cell survival. Exposure of human neuroblastoma SH-SY5Y cells of up to 2 MUM MeHg phosphorylated Akt and its downstream signal molecule CREB, presumably due to inactivation of PTEN through S-mercuration. As a result, the anti-apoptotic protein Bcl-2 was up-regulated by MeHg. The activation of Akt/CREB/Bcl-2 signaling mediated by MeHg was, at least in part, linked to cellular defence because either pretreatment with wortmannin to block PI3K/Akt signaling or knockdown of Bcl-2 enhanced MeHg-mediated cytotoxicity. In contrast, increasing concentrations of MeHg disrupted Akt/CREB/Bcl-2 signaling. This phenomenon was attributed to S-mercuration of CREB through Cys286 rather than Akt. These results suggest that although MeHg is an apoptosis-inducing toxicant, this environmental electrophile is able to activate the cell survival signal transduction pathway at lower concentrations prior to apoptotic cell death. PMID- 27357942 TI - Evaluation of breeding strategies for polledness in dairy cattle using a newly developed simulation framework for quantitative and Mendelian traits. AB - BACKGROUND: Intensified selection of polled individuals has recently gained importance in predominantly horned dairy cattle breeds as an alternative to routine dehorning. The status quo of the current polled breeding pool of genetically-closely related artificial insemination sires with lower breeding values for performance traits raises questions regarding the effects of intensified selection based on this founder pool. METHODS: We developed a stochastic simulation framework that combines the stochastic simulation software QMSim and a self-designed R program named QUALsim that acts as an external extension. Two traits were simulated in a dairy cattle population for 25 generations: one quantitative (QMSim) and one qualitative trait with Mendelian inheritance (i.e. polledness, QUALsim). The assignment scheme for qualitative trait genotypes initiated realistic initial breeding situations regarding allele frequencies, true breeding values for the quantitative trait and genetic relatedness. Intensified selection for polled cattle was achieved using an approach that weights estimated breeding values in the animal best linear unbiased prediction model for the quantitative trait depending on genotypes or phenotypes for the polled trait with a user-defined weighting factor. RESULTS: Selection response for the polled trait was highest in the selection scheme based on genotypes. Selection based on phenotypes led to significantly lower allele frequencies for polled. The male selection path played a significantly greater role for a fast dissemination of polled alleles compared to female selection strategies. Fixation of the polled allele implies selection based on polled genotypes among males. In comparison to a base breeding scenario that does not take polledness into account, intensive selection for polled substantially reduced genetic gain for this quantitative trait after 25 generations. Reducing selection intensity for polled males while maintaining strong selection intensity among females, simultaneously decreased losses in genetic gain and achieved a final allele frequency of 0.93 for polled. CONCLUSIONS: A fast transition to a completely polled population through intensified selection for polled was in contradiction to the preservation of high genetic gain for the quantitative trait. Selection on male polled genotypes with moderate weighting, and selection on female polled phenotypes with high weighting, could be a suitable compromise regarding all important breeding aspects. PMID- 27357940 TI - Effect of low doses of estradiol and tamoxifen on breast cancer cell karyotypes. AB - Evidence supports a role of 17&-estradiol (E2) in carcinogenesis and the large majority of breast carcinomas are dependent on estrogen. The anti-estrogen tamoxifen (TAM) is widely used for both treatment and prevention of breast cancer; however, it is also carcinogenic in human uterus and rat liver, highlighting the profound complexity of its actions. The nature of E2- or TAM induced chromosomal damage has been explored using relatively high concentrations of these agents, and only some numerical aberrations and chromosomal breaks have been analyzed. This study aimed to determine the effects of low doses of E2 and TAM (10(&8 )mol L(&1) and 10(&6 )mol L(&1) respectively) on karyotypes of MCF7, T47D, BT474, and SKBR3 breast cancer cells by comparing the results of conventional karyotyping and multi-FISH painting with cell proliferation. Estrogen receptor (ER)-positive (+) cells showed an increase in cell proliferation after E2 treatment (MCF7, T47D, and BT474) and a decrease after TAM treatment (MCF7 and T47D), whereas in ER& cells (SKBR3), no alterations in cell proliferation were observed, except for a small increase at 96 h. Karyotypes of both ER+ and ER& breast cancer cells increased in complexity after treatments with E2 and TAM leading to specific chromosomal abnormalities, some of which were consistent throughout the treatment duration. This genotoxic effect was higher in HER2+ cells. The ER&/HER2+ SKBR3 cells were found to be sensitive to TAM, exhibiting an increase in chromosomal aberrations. These in vitro results provide insights into the potential role of low doses of E2 and TAM in inducing chromosomal rearrangements in breast cancer cells. PMID- 27357943 TI - Evaluation of fertility in relation to milk production and productivity of Murrah buffaloes. AB - Intense selection of buffaloes for milk production at organized herds of the country without giving due attention to fertility traits has lead to deterioration in their performances. The study was initiated to assess the relationship between milk production and productivity with fertility in Murrah buffaloes. In the present study, fertility was defined in terms of pregnancy rate of Murrah buffaloes. Pregnancy rate measures the percentage of non-pregnant animals that become pregnant during each oestrous cycle. Data pertaining to 1224 lactation records of Murrah buffaloes spread over a period 22 years from 1993 to 2014 were analyzed in the study. It was observed that pregnancy rate is negatively associated with 305days or less milk yield (-0.08+/-0.04) and wet average (-0.12+/-0.02) and positively associated with life time (0.15+/-0.03) in Murrah buffaloes. Wet average is defined as average daily milk yield per lactation of Murrah buffaloes. To achieve around 2000kg 305days or less milk yield and 7.5kg wet average, the level of pregnancy rate in Murrah buffaloes should vary between 30 and 50%. The per unit change in pregnancy rate with respect to milk yield in Murrah buffaloes, were studied using regression analysis. The results suggest that increasing hundred kilogram in 305days or one kilogram milk yield per day in 305days, pregnancy rate reduced by 0.9% in overall lactations of Murrah buffaloes. By increasing hundred kilogram life time 305days or less milk yield and one kilogram life time wet average, pregnancy rate of Murrah buffaloes reduced by about 0.2% and 0.34%, respectively. The study quantifies the decline of pregnancy rate with increase of lactation milk yield and wet average in Murrah buffaloes and emphasis the importance of fertility i.e. pregnancy rate in the evaluation and breeding programmes of Murrah buffaloes. PMID- 27357944 TI - Stepwise Unfolding of Single-Chain Nanoparticles by Chemically Triggered Gates. AB - The orthogonal, stepwise, and order-independent unfolding of single-chain nanoparticles (SCNPs) is introduced as a key step towards actively controlling the folding dynamics of SCNPs. The SCNPs are compacted by multiple hydrogen bonds and host-guest interactions. Well-defined diblock (AB) and tetrablock (ABCD) copolymers are equipped with orthogonal recognition motifs via modular ligation along the lateral chain. Initially, single-chain folding of the diblock copolymer was induced by the host-guest complexation of benzo-21-crown-7 (B21C7, host) and a secondary ammonium salt (AS, guest), representing an efficient avenue for single-chain collapse. Next, both orthogonal Hamilton wedge (HW) and cyanuric acid (CA) as well as B21C7-AS motifs were employed to generate SCNPs based on the ABCD polymer system. Subsequently, the stepwise dual-gated and order-independent unfolding of the SCNPs was investigated by the addition of external stimuli. The folding and unfolding were explored by 1D (1) H NMR spectroscopy, dynamic light scattering (DLS), and diffusion-ordered NMR spectroscopy (DOSY). PMID- 27357945 TI - [Patella navigation in computer-assisted TKA : Intraoperative measurement of patellar kinematics. Video article]. AB - INTRODUCTION: Patellofemoral maltracking is a relevant problem after total knee arthroplasty (TKA). Patella navigation is a tool that allows real time monitoring of patella tracking. MATERIAL: This video contribution demonstrates the technique of patellofemoral navigation and a possible consequence of intraoperative monitoring. A higher postoperative lateral tilt is addressed with a widening of the lateral retinaculum in a particular manner. CONCLUSION: In selected cases of patellofemoral problems, patella navigation is a helpful tool to evaluate patellofemoral tracking intraoperatively. Modifications of implant position and soft tissue measurements can then prevent postoperative patellofemoral maltracking. PMID- 27357946 TI - Simultaneous Tc-99m and I-123 dual-radionuclide imaging with a solid-state detector-based brain-SPECT system and energy-based scatter correction. AB - BACKGROUND: A brain single-photon emission computed tomography (SPECT) system using cadmium telluride (CdTe) solid-state detectors was previously developed. This CdTe-SPECT system is suitable for simultaneous dual-radionuclide imaging due to its fine energy resolution (6.6 %). However, the problems of down-scatter and low-energy tail due to the spectral characteristics of a pixelated solid-state detector should be addressed. The objective of this work was to develop a system for simultaneous Tc-99m and I-123 brain studies and evaluate its accuracy. METHODS: A scatter correction method using five energy windows (FiveEWs) was developed. The windows are Tc-lower, Tc-main, shared sub-window of Tc-upper and I lower, I-main, and I-upper. This FiveEW method uses pre-measured responses for primary gamma rays from each radionuclide to compensate for the overestimation of scatter by the triple-energy window method that is used. Two phantom experiments and a healthy volunteer experiment were conducted using the CdTe-SPECT system. A cylindrical phantom and a six-compartment phantom with five different mixtures of Tc-99m and I-123 and a cold one were scanned. The quantitative accuracy was evaluated using 18 regions of interest for each phantom. In the volunteer study, five healthy volunteers were injected with Tc-99m human serum albumin diethylene triamine pentaacetic acid (HSA-D) and scanned (single acquisition). They were then injected with I-123 N-isopropyl-4-iodoamphetamine hydrochloride (IMP) and scanned again (dual acquisition). The counts of the Tc-99m images for the single and dual acquisitions were compared. RESULTS: In the cylindrical phantom experiments, the percentage difference (PD) between the single and dual acquisitions was 5.7 +/- 4.0 % (mean +/- standard deviation). In the six compartment phantom experiment, the PDs between measured and injected activity for Tc-99m and I-123 were 14.4 +/- 11.0 and 2.3 +/- 1.8 %, respectively. In the volunteer study, the PD between the single and dual acquisitions was 4.5 +/- 3.4 %. CONCLUSIONS: This CdTe-SPECT system using the FiveEW method can provide accurate simultaneous dual-radionuclide imaging. A solid-state detector SPECT system using the FiveEW method will permit quantitative simultaneous Tc-99m and I 123 study to become clinically applicable. PMID- 27357949 TI - How molecular is the chemisorptive bond? AB - Trends in adsorption energies as a function of transition metal differ for adsorbates that are attached atop a surface atom or are adsorbed onto a high coordination site. When adsorption onto early and late transition metals is compared variation in relative bond energies of adsorbates attached to different sites is large. A theoretical understanding is provided based on the analysis of the electronic structure of the respective chemical bonds. The electronic structure analysis is based on partial density of states (PDOS) and bond order overlap population densities from crystal orbital Hamiltonian population (COHP) calculations available from DFT electronic structure computations. This is complemented by calculations of Bader charge densities and electron density topology properties. Variation of the respective bond energies depends on the symmetry of the molecular orbitals that form the chemical bond. The key electronic structure parameters are the position of the Fermi level in the bonding or antibonding molecular orbital partial density of states region of the chemical bond and chemical bond polarity. These are very different for adsorbates adsorbed onto the same transition metal surface, but which have different coordination with surface metal atoms. The adsorption energies and the respective electronic structures of adatoms H, C and O and molecular fragments CHx (x = 1-3) are compared with those of the analogous molecules that contain a single transition metal atom. When adsorbed atop, trends in bond energies are remarkably similar to those of the corresponding molecules. The difference in bond energies of adsorbates and transition metal molecules, i.e. the embedding energy, is shown to consist of three contributions: quenching of the sometimes high molecular spin states, weakening of the adsorbate-surface interaction energy and weakening of the metal-metal atom bond energies next to the adsorbate. Conventional scaling rules of the interaction energies of adsorbed CHx (0 < x <= 3) fragments are satisfied only for adsorbates in high coordination sites. For the early transition metals a breaking of this rule is found for C and CH or N and NH when adsorbed atop a transition metal surface or when they are part of a transition metal molecule. The M-C bond energy is found to be only stronger than that of the M-CH bond as long as the Fermi level or the HOMO is located in the antibonding molecular orbital partial density of states of the chemical bond. PMID- 27357948 TI - Establishing and validating regulatory regions for variant annotation and expression analysis. AB - BACKGROUND: The regulatory effect of inherited or de novo genetic variants occurring in promoters as well as in transcribed or even coding gene regions is gaining greater recognition as a contributing factor to disease processes in addition to mutations affecting protein functionality. Thousands of such regulatory mutations are already recorded in HGMD, OMIM, ClinVar and other databases containing published disease causing and associated mutations. It is therefore important to properly annotate genetic variants occurring in experimentally verified and predicted transcription factor binding sites (TFBS) that could thus influence the factor binding event. Selection of the promoter sequence used is an important factor in the analysis as it directly influences the composition of the sequence available for transcription factor binding analysis. RESULTS: In this study we first establish genomic regions likely to be involved in regulation of gene expression. TRANSFAC uses a method of virtual transcription start sites (vTSS) calculation to define the best supported promoter for a gene. We have performed a comparison of the virtually calculated promoters between the best supported and secondary promoters in hg19 and hg38 reference genomes to test and validate the approach. Next we create and utilize a workflow for systematic analysis of casual disease associated variants in TFBS using Genome Trax and TRANSFAC databases. A total of 841 and 736 experimentally verified TFBSs within best supported promoters were mapped over HGMD and ClinVar mutation sites respectively. Tens of thousands of predicted ChIP-Seq derived TFBSs were mapped over mutations as well. We have further analyzed some of these mutations for potential gain or loss in transcription factor binding. CONCLUSIONS: We have confirmed the validity of TRANSFAC's approach to define the best supported promoters and established a workflow of their use in annotation of regulatory genetic variants. PMID- 27357947 TI - Acetate functions as an epigenetic metabolite to promote lipid synthesis under hypoxia. AB - Besides the conventional carbon sources, acetyl-CoA has recently been shown to be generated from acetate in various types of cancers, where it promotes lipid synthesis and tumour growth. The underlying mechanism, however, remains largely unknown. We find that acetate induces a hyperacetylated state of histone H3 in hypoxic cells. Acetate predominately activates lipogenic genes ACACA and FASN expression by increasing H3K9, H3K27 and H3K56 acetylation levels at their promoter regions, thus enhancing de novo lipid synthesis, which combines with its function as the metabolic precursor for fatty acid synthesis. Acetyl-CoA synthetases (ACSS1, ACSS2) are involved in this acetate-mediated epigenetic regulation. More importantly, human hepatocellular carcinoma with high ACSS1/2 expression exhibit increased histone H3 acetylation and FASN expression. Taken together, this study demonstrates that acetate, in addition to its ability to induce fatty acid synthesis as an immediate metabolic precursor, also functions as an epigenetic metabolite to promote cancer cell survival under hypoxic stress. PMID- 27357950 TI - Nitroglycerin induces DNA damage and vascular cell death in the setting of nitrate tolerance. AB - Nitroglycerin (GTN) and other organic nitrates are widely used vasodilators. Their side effects are development of nitrate tolerance and endothelial dysfunction. Given the potential of GTN to induce nitro-oxidative stress, we investigated the interaction between nitro-oxidative DNA damage and vascular dysfunction in experimental nitrate tolerance. Cultured endothelial hybridoma cells (EA.hy 926) and Wistar rats were treated with GTN (ex vivo: 10-1000 uM; in vivo: 10, 20 and 50 mg/kg/day for 3 days, s.c.). The level of DNA strand breaks, 8-oxoguanine and O (6)-methylguanine DNA adducts was determined by Comet assay, dot blot and immunohistochemistry. Vascular function was determined by isometric tension recording. DNA adducts and strand breaks were induced by GTN in cells in vitro in a concentration-dependent manner. GTN in vivo administration leads to endothelial dysfunction, nitrate tolerance, aortic and cardiac oxidative stress, formation of DNA adducts, stabilization of p53 and apoptotic death of vascular cells in a dose-dependent fashion. Mice lacking O (6)-methylguanine-DNA methyltransferase displayed more vascular O (6)-methylguanine adducts and oxidative stress under GTN therapy than wild-type mice. Although we were not able to prove a causal role of DNA damage in the etiology of nitrate tolerance, the finding of GTN-induced DNA damage such as the mutagenic and toxic adduct O (6) methylguanine, and cell death supports the notion that GTN based therapy may provoke adverse side effects, including endothelial function. Further studies are warranted to clarify whether GTN pro-apoptotic effects are related to an impaired recovery of patients upon myocardial infarction. PMID- 27357951 TI - Effectiveness of vegetation-based biodiversity offset metrics as surrogates for ants. AB - Biodiversity offset schemes are globally popular policy tools for balancing the competing demands of conservation and development. Trading currencies for losses and gains in biodiversity value at development and credit sites are usually based on several vegetation attributes combined to yield a simple score (multimetric), but the score is rarely validated prior to implementation. Inaccurate biodiversity trading currencies are likely to accelerate global biodiversity loss through unrepresentative trades of losses and gains. We tested a model vegetation multimetric (i.e., vegetation structural and compositional attributes) typical of offset trading currencies to determine whether it represented measurable components of compositional and functional biodiversity. Study sites were located in remnant patches of a critically endangered ecological community in western Sydney, Australia, an area representative of global conflicts between conservation and expanding urban development. We sampled ant fauna composition with pitfall traps and enumerated removal by ants of native plant seeds from artificial seed containers (seed depots). Ants are an excellent model taxon because they are strongly associated with habitat complexity, respond rapidly to environmental change, and are functionally important at many trophic levels. The vegetation multimetric did not predict differences in ant community composition or seed removal, despite underlying assumptions that biodiversity trading currencies used in offset schemes represent all components of a site's biodiversity value. This suggests that vegetation multimetrics are inadequate surrogates for total biodiversity value. These findings highlight the urgent need to refine existing offsetting multimetrics to ensure they meet underlying assumptions of surrogacy. Despite the best intentions, offset schemes will never achieve their goal of no net loss of biodiversity values if trades are based on metrics unrepresentative of total biodiversity. PMID- 27357953 TI - Community's perceptions of pre-eclampsia and eclampsia in Sindh Pakistan: a qualitative study. AB - BACKGROUND: Maternal mortality is of global public health concern and >99 % of maternal deaths occur in less developed countries. The common causes of direct maternal death are hemorrhage, sepsis and pre-eclampsia/eclampsia. In Pakistan, pre-eclampsia/eclampsia deaths represents one-third of maternal deaths reported at the tertiary care hospital settings. This study explored community perceptions, and traditional management practices about pre-eclampsia/eclampsia. METHODS: A qualitative study was conducted in Sindh Province of Pakistan from February to July 2012. Twenty-six focus groups were conducted, 19 with women of reproductive age/mothers-in-law (N = 173); and 7 with husbands/fathers-in-law (N = 65). The data were transcribed verbatim in Sindhi and Urdu, then analyzed for emerging themes and sub-themes using NVivo version 10 software. RESULTS: Pre eclampsia in pregnancy was not recognized as a disease and there was no name in the local languages to describe this. Women however, knew about high blood pressure and were aware they can develop it during pregnancy. It was widely believed that stress and weakness caused high blood pressure in pregnancy and it caused symptoms of headache. The perception of high blood pressure was not based on measurement but on symptoms. Self-medication was often used for headaches associated with high blood pressure. They were also awareness that severely high blood pressure could result in death. CONCLUSIONS: Community-based participatory health education strategies are recommended to dispel myths and misperceptions regarding pre-eclampsia and eclampsia. The educational initiatives should include information on the presentation, progression of illness, danger signs associated with pregnancy, and appropriate treatment. PMID- 27357952 TI - Utility of CSF biomarkers in psychiatric disorders: a national multicentre prospective study. AB - BACKGROUND: Affective and psychotic disorders are mental or behavioural patterns resulting in an inability to cope with life's ordinary demands and routines. These conditions can be a prodromal event of Alzheimer's disease (AD). The prevalence of underlying AD lesions in psychiatric diseases is unknown, and it would be helpful to determine them in patients. AD cerebrospinal fluid (CSF) biomarkers (amyloid beta, tau and phosphorylated tau) have high diagnostic accuracy, both for AD with dementia and to predict incipient AD (mild cognitive impairment due to AD), and they are sometimes used to discriminate psychiatric diseases from AD. Our objective in the present study was to evaluate the clinical utility of CSF biomarkers in a group of patients with psychiatric disease as the main diagnosis. METHODS: In a multicentre prospective study, clinicians filled out an anonymous questionnaire about all of their patients who had undergone CSF biomarker evaluation. Before and after CSF biomarker results were obtained, clinicians provided a diagnosis with their level of confidence and information about the treatment. We included patients with a psychiatric disorder as the initial diagnosis. In a second part of the study conducted retrospectively in a followed subgroup, clinicians detailed the psychiatric history and we classified patients into three categories: (1) psychiatric symptoms associated with AD, (2) dual diagnosis and (3) cognitive decline not linked to a neurodegenerative disorder. RESULTS: Of 957 patients, 69 had an initial diagnosis of a psychiatric disorder. Among these 69 patients, 14 (20.2 %) had a CSF AD profile, 5 (7.2 %) presented with an intermediate CSF profile and 50 (72.4 %) had a non-AD CSF profile. Ultimately, 13 (18.8 %) patients were diagnosed with AD. We show that in the AD group psychiatric symptoms occurred later and the delay between the first psychiatric symptoms and the cognitive decline was shorter. CONCLUSIONS: This study revealed that about 20 % of patients with a primary psychiatric disorder diagnosis before undergoing a CSF exploration for cognitive disorder displayed a CSF biomarker AD profile. In memory clinics, it seems important to consider AD as a possible diagnosis before finalizing a diagnosis of a psychiatric disorder. PMID- 27357954 TI - Just one look: Direct gaze briefly disrupts visual working memory. AB - Direct gaze is a salient social cue that affords rapid detection. A body of research suggests that direct gaze enhances performance on memory tasks (e.g., Hood, Macrae, Cole-Davies, & Dias, Developmental Science, 1, 67-71, 2003). Nonetheless, other studies highlight the disruptive effect direct gaze has on concurrent cognitive processes (e.g., Conty, Gimmig, Belletier, George, & Huguet, Cognition, 115(1), 133-139, 2010). This discrepancy raises questions about the effects direct gaze may have on concurrent memory tasks. We addressed this topic by employing a change detection paradigm, where participants retained information about the color of small sets of agents. Experiment 1 revealed that, despite the irrelevance of the agents' eye gaze to the memory task at hand, participants were worse at detecting changes when the agents looked directly at them compared to when the agents looked away. Experiment 2 showed that the disruptive effect was relatively short-lived. Prolonged presentation of direct gaze led to recovery from the initial disruption, rather than a sustained disruption on change detection performance. The present study provides the first evidence that direct gaze impairs visual working memory with a rapidly-developing yet short-lived effect even when there is no need to attend to agents' gaze. PMID- 27357955 TI - Sex differences in visual-spatial working memory: A meta-analysis. AB - Visual-spatial working memory measures are widely used in clinical and experimental settings. Furthermore, it has been argued that the male advantage in spatial abilities can be explained by a sex difference in visual-spatial working memory. Therefore, sex differences in visual-spatial working memory have important implication for research, theory, and practice, but they have yet to be quantified. The present meta-analysis quantified the magnitude of sex differences in visual-spatial working memory and examined variables that might moderate them. The analysis used a set of 180 effect sizes from healthy males and females drawn from 98 samples ranging in mean age from 3 to 86 years. Multilevel meta-analysis was used on the overall data set to account for non-independent effect sizes. The data also were analyzed in separate task subgroups by means of multilevel and mixed-effects models. Results showed a small but significant male advantage (mean d = 0.155, 95 % confidence interval = 0.087-0.223). All the tasks produced a male advantage, except for memory for location, where a female advantage emerged. Age of the participants was a significant moderator, indicating that sex differences in visual-spatial working memory appeared first in the 13-17 years age group. Removing memory for location tasks from the sample affected the pattern of significant moderators. The present results indicate a male advantage in visual spatial working memory, although age and specific task modulate the magnitude and direction of the effects. Implications for clinical applications, cognitive model building, and experimental research are discussed. PMID- 27357956 TI - Sensitivity to value-driven attention is predicted by how we learn from value. AB - Reward learning is known to influence the automatic capture of attention. This study examined how the rate of learning, after high- or low-value reward outcomes, can influence future transfers into value-driven attentional capture. Participants performed an instrumental learning task that was directly followed by an attentional capture task. A hierarchical Bayesian reinforcement model was used to infer individual differences in learning from high or low reward. Results showed a strong relationship between high-reward learning rates (or the weight that is put on learning after a high reward) and the magnitude of attentional capture with high-reward colors. Individual differences in learning from high or low rewards were further related to performance differences when high- or low value distractors were present. These findings provide novel insight into the development of value-driven attentional capture by showing how information updating after desired or undesired outcomes can influence future deployments of automatic attention. PMID- 27357957 TI - A 3-D net based on weak metallophilic (CuCu) interactions. AB - A novel 3-D binary copper(i) polymer [Cu(IN)]n (1, IN = isonicotinate) has been solvothermally synthesized. 1-D [Cu(IN)] chains of 1 are interconnected by weak metallophilic (CuCu) interactions to form a 3-D net. The theoretical band structure and photocatalytic and fluorescence properties have also been studied. PMID- 27357958 TI - Plasma levels of eight different mediators and their potential as biomarkers of various clinical malaria conditions in African children. AB - BACKGROUND: Plasmodium falciparum infection can lead to several clinical manifestations ranging from asymptomatic infections (AM) and uncomplicated malaria (UM) to potentially fatal severe malaria (SM), including cerebral malaria (CM). Factors implicated in the progression towards severe disease are not fully understood. METHODS: In the present study, an enzyme-linked immunosorbent assay (ELISA) method was used to investigate the plasma content of several biomarkers of the immune response, namely Neopterin, sCD163, suPAR, Pentraxin 3 (PTX3), sCD14, Fractalkine (CX3CL1), sTREM-1 and MIG (CXCL9), in patients with distinct clinical manifestations of malaria. The goal of this study was to determine the relative involvement of these inflammatory mediators in the pathogenesis of malaria and test their relevance as biomarkers of disease severity. RESULTS: ROC curve analysis show that children with AM were characterized by high levels of Fractalkine and sCD163 whereas children with UM were distinguishable by the presence of PTX3 in their plasma. Furthermore, principal component analysis indicated that the combination of Fractalkine, MIG, and Neopterin was the best predictor of AM condition, while suPAR, PTX3 and sTREM-1 combination was the best indicator of UM when compared to AM. The association of Neopterin, suPAR and Fractalkine was strongly predictive of SM or CM compared to UM. CONCLUSIONS: The results indicate that the simultaneous evaluation of these bioactive molecules as quantifiable blood parameters may be helpful to get a better insight into the clinical syndromes in children with malaria. PMID- 27357959 TI - Development of high-lysine rice via endosperm-specific expression of a foreign LYSINE RICH PROTEIN gene. AB - BACKGROUND: Lysine (Lys) is considered to be the first limiting essential amino acid in rice. Although there have been extensive efforts to improve the Lys content of rice through traditional breeding and genetic engineering, no satisfactory products have been achieved to date. RESULTS: We expressed a LYSINE RICH PROTEIN gene (LRP) from Psophocarpus tetragonolobus (L.) DC using an endosperm-specific GLUTELIN1 promoter (GT1) in Peiai64S (PA64S), an elite photoperiod-thermo sensitive male sterility (PTSMS) line. The expression of the foreign LRP protein was confirmed by Western blot analysis. The Lys level in the transgenic rice seeds increased more than 30 %, the total amount of other amino acids also increased compared to wild-type. Persistent investigation of amino acids in 3 generations showed that the Lys content was significantly increased in seeds of transgenic rice. Furthermore, Lys content in the hybrid of the transgenic plants also had an approximate 20 % increase compared to hybrid control. At the grain-filling stage, we monitored the transcript abundance of many genes encoding key enzymes involved in amino acid metabolism, and the results suggested that reduced amino acid catabolism led to the accumulation of amino acids in the transgenic plants. The genetically engineered rice showed unfavorable grain phenotypes compared to wild-type, however, its hybrid displayed little negative effects on grain. CONCLUSIONS: Endosperm-specific expression of foreign LRP significantly increased the Lys content in the seeds of transgenic plant, and the the Lys increase was stably heritable with 3 generation investigation. The hybrid of the transgenic plants also showed significant increases of Lys content in the seeds. These results indicated that expression of LRP in rice seeds may have promising applications in improving Lys levels in rice. PMID- 27357960 TI - [Open-wedge osteotomy of the glenoid for treatment of posterior shoulder instability with increased glenoid retroversion]. AB - OBJECTIVE: Treatment of posterior shoulder instability with increased retroversion of the glenoid using open-wedge osteotomy of the glenoid neck stabilized with an autologous bone block. INDICATIONS: Symptomatic, atraumatic posterior shoulder instability with increased retroversion (>20 degrees ) of the glenoid and previously failed conservative or surgical treatment. CONTRAINDICATIONS: General contraindications against surgery. Relative contraindications: osteoporosis, nicotine abuse, or suspected patient noncompliance. SURGICAL TECHNIQUE: Posterior approach with a 7 cm long incision starting medial of the posterolateral corner of the acromion heading to the posterior axillary fold and subsequent preparation of the deltoid muscle and the infraspinatus muscle. The posterior glenohumeral capsule is incised by performing a capsular T-shift. The osteotomy is performed intracapsulary medial to the genoid rim. The wedge bone graft, harvested from spina scapulae or iliac spine, is placed "press fit" in position. Additional fixation of the graft is not necessary if the anterior cortex is intact. For reinforcing the posterior capsule, a posterior capsule shift should be performed. Insertion of extracapsular wound drainage. Successive wound closure. POSTOPERATIVE MANAGEMENT: Postoperative immobilization in a 0 degrees shoulder orthesis for 6 weeks; avoidance of horizontal abduction for 8 weeks. After removing the wound drainage, start of limited active-assisted range of motion. Over-head sports after 6 months. RESULTS: From 2009-2015, 6 posterior open wedge glenoid osteotomies were performed. Postoperative retroversion of the glenoid was 11.2 +/- 9.4 degrees compared to 26.0 +/- 8.6 degrees before surgery. Of 6 shoulders, 2 showed postoperative signs of persistent posterior instability; the other 4 shoulders were free of complaints. No revision surgery was needed. PMID- 27357961 TI - Mechanism of osteogenic and adipogenic differentiation of tendon stem cells induced by sirtuin 1. AB - The aim of the present study was to assess the expression of sirtuin (Sirt)1 in tendon stem cells (TSCs) and to elucidate its association with osteogenic and adipogenic differentiation of TSCs. Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analyses were performed to detect Sirt1 mRNA and protein levels in TSCs, respectively. TSCs were positive for Sirt1 expression, which was elevated by Sirt1 activator SRT1720 in a time- and concentration- dependent manner, and decreased by Sirt1 inhibitor EX527. TSCs were treated with SRT1720 and EX527 for various time periods and resulting changes in osteogenic and adipogenic protein markers were analyzed using alizarin red and oil red O staining. According to RT-qPCR and western blot analyses, the associated factors beta-catenin, Runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 2 were elevated following increases of Sirt1 levels, while CCAAT/enhancer binding protein (CEBP)alpha and peroxisome proliferator activated receptor (PPAR)gamma were decreased. These results suggested that osteogenic differentiation capacity was enhanced, while adipogenic differentiation capacity declined. Further mechanistic study revealed that phosphoinositide-3 kinase (PI3K) and AKT were decreased following activation of Sirt1. In conclusion, the present study suggested that Sirt1 promotes the osteogenic differentiation of TSCs through upregulating beta-catenin and Runx2 and inhibits the adipogenic differentiation of TSCs through the PI3K/AKT pathway with downregulation of CEBPalpha and PPARgamma. PMID- 27357962 TI - Doctors give patients potentially harmful procedures at end of life, global review finds. PMID- 27357964 TI - Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science : Seattle, WA, USA. 24-26 September 2015. PMID- 27357963 TI - Anti-melanin deposition activity of ceramicines from Chisocheton ceramicus. AB - The ceramicines, a series of limonoids from Chisocheton ceramicus (Meliaceae), were evaluated for anti-melanin deposition activity on alpha-melanocyte stimulating hormone (alpha-MSH) and 3-isobutyl-1-methylxanthine (IBMX)-treated B16-F10 melanoma cell, and several ceramicines were found to be active. The structure-activity relationship of ceramicines as anti-melanin deposition inhibitors was deduced. Furthermore, the mechanism of anti-melanin deposition activity of ceramicine B, a major constituent of C. ceramicus that showed potent anti-melanin deposition activity, was investigated. Tyrosinase enzymatic activity and tyrosinase mRNA expression were not affected by ceramicine B. The anti melanin deposition activity of ceramicine B was shown to be related to the downregulation of tyrosinase protein expression. These results suggest that ceramicines have potential to be used as depigmentation agents. PMID- 27357965 TI - Clinical prediction rules in Staphylococcus aureus bacteremia demonstrate the usefulness of reporting likelihood ratios in infectious diseases. AB - Infectious diseases specialists often use diagnostic tests to assess the probability of a disease based on knowledge of the diagnostic properties. It has become standard for published studies on diagnostic tests to report sensitivity, specificity and predictive values. Likelihood ratios are often omitted. We compared published clinical prediction rules in Staphylococcus aureus bacteremia to illustrate the importance of likelihood ratios. We performed a narrative review comparing published clinical prediction rules used for excluding endocarditis in S. aureus bacteremia. Of nine published clinical prediction rules, only three studies reported likelihood ratios. Many studies concluded that the clinical prediction rule could safely exclude endocarditis based on high sensitivity and high negative predictive value. Of the studies with similar high sensitivity and high negative predictive value, calculated negative likelihood ratios were able to differentiate and identify the best clinical prediction rule for excluding endocarditis. Compared to sensitivity, specificity and predictive values, likelihood ratios can be more directly used to interpret diagnostic test results to assist in ruling in or ruling out a disease. Therefore, a new standard should be set to include likelihood ratios in reporting of diagnostic tests in infectious diseases research. PMID- 27357966 TI - Inhomogeneous Point-Processes to Instantaneously Assess Affective Haptic Perception through Heartbeat Dynamics Information. AB - This study proposes the application of a comprehensive signal processing framework, based on inhomogeneous point-process models of heartbeat dynamics, to instantaneously assess affective haptic perception using electrocardiogram derived information exclusively. The framework relies on inverse-Gaussian point processes with Laguerre expansion of the nonlinear Wiener-Volterra kernels, accounting for the long-term information given by the past heartbeat events. Up to cubic-order nonlinearities allow for an instantaneous estimation of the dynamic spectrum and bispectrum of the considered cardiovascular dynamics, as well as for instantaneous measures of complexity, through Lyapunov exponents and entropy. Short-term caress-like stimuli were administered for 4.3-25 seconds on the forearms of 32 healthy volunteers (16 females) through a wearable haptic device, by selectively superimposing two levels of force, 2 N and 6 N, and two levels of velocity, 9.4 mm/s and 65 mm/s. Results demonstrated that our instantaneous linear and nonlinear features were able to finely characterize the affective haptic perception, with a recognition accuracy of 69.79% along the force dimension, and 81.25% along the velocity dimension. PMID- 27357968 TI - The Geriatric Nutritional Risk Index is Independently Associated with Prognosis in Patients with Critical Limb Ischemia Following Endovascular Therapy. AB - OBJECTIVES: Patients with critical limb ischemia (CLI) have poor overall and limb prognosis. Although nutritional status influences overall prognosis, and the Geriatric Nutritional Risk Index (GNRI) is a widely used, simple and well established nutritional status screening method, the association between the GNRI and the overall and limb prognosis of patients with CLI following endovascular therapy (EVT) has not been explored. METHODS: Clinical outcomes were retrospectively evaluated in 473 consecutive patients (74 +/- 10 years; 59% male) with CLI who underwent EVT. The GNRI on admission was calculated as follows: [14.89 * albumin (g/dL)] + [41.7 * (body weight/ideal body weight)]. Cox proportional hazard analysis was performed to explore the independent association between the GNRI and mortality and major amputation. RESULTS: Patients (53% ambulatory, 38% wheelchair bound, and 9% bedridden) were divided into two groups based on the median GNRI: the higher group (GNRI >= 91.2, n = 237) and the lower group (GNRI < 91.2, n = 236). Median follow up duration after EVT was 11.3 months. Three years after EVT, the survival rate (74% in the higher GNRI, and 48% in the lower GNRI, respectively), and limb salvage rate (92% in the higher GNRI, and 84% in the lower GNRI) were significantly lower in the lower GNRI group. GNRI (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01-1.05), along with being wheelchair bound (HR, 1.87; 95% CI 1.17-2.97; vs. ambulatory status), being bedridden (HR, 3.10; 95% CI, 1.63-2.97; vs. ambulatory status), being on hemodialysis (HR, 2.33; 95% CI, 1.49-3.64), and having chronic heart failure (HR, 2.22; 95% CI, 1.44-3.43) were the independent predictors of mortality. The GNRI (HR, 1.04; 95% CI, 1.01-1.07), being bedridden (HR, 4.15; 95% CI, 1.67-10.3; vs. ambulatory status), isolated below knee disease (HR, 2.49; 95% CI, 1.30-4.77), and hemodialysis (HR, 2.44; 95% CI, 1.23-4.85) were independently associated with major amputation. CONCLUSIONS: The GNRI on admission was independently associated with mortality and major amputation after EVT in patients with CLI. PMID- 27357969 TI - The effect of a finger training application using a tablet PC in chronic hemiparetic stroke patients. AB - Twenty-one consecutive patients were randomly assigned to either the intervention group (10 patients) or the control group (11 patients). The application consisted of three sections (registration, evaluation, and training) and the training section consisted of five programs (stretching, flexion, extension, opposition, and thumb abduction). Application training consisted of 1 session (31 min)/day, 6 days/week for 4 weeks. We found that our application training was effective in terms of the motor function of the affected hand: Manual Muscle Test of the wrist and finger extensors, the Manual Function Test (subtest of manipulative activity), and the Purdue Pegboard Test. PMID- 27357970 TI - An Analytical Solution for Exciton Generation, Reaction, and Diffusion in Nanotube and Nanowire-Based Solar Cells. AB - Excitonic solar cells based on aligned or unaligned networks of nanotubes or nanowires offer advantages with respect of optical absorption, and control of excition and electrical carrier transport; however, there is a lack of predictive models of the optimal orientation and packing density of such devices to maximize efficiency. Here-in, we develop a concise analytical framework that describes the orientation and density trade-off on exciton collection computed from a deterministic model of a carbon nanotube (CNT) photovoltaic device under steady state operation that incorporates single- and aggregate-nanotube photophysics published earlier (Energy Environ Sci, 2014, 7, 3769). We show that the maximal film efficiency is determined by a parameter grouping, alpha, representing the product of the network density and the effective exciton diffusion length, reflecting a cooperativity between the rate of exciton generation and the rate of exciton transport. This allows for a simple, master plot of EQE versus film thickness, parametric in alpha allowing for optimal design. This analysis extends to any excitonic solar cell with anisotropic transport elements, including polymer, nanowire, quantum dot, and nanocarbon photovoltaics. PMID- 27357971 TI - Celecoxib Versus Placebo in Tonsillectomy: A Prospective, Randomized, Double Blind Placebo-Controlled Trial. AB - OBJECTIVES: Celecoxib is a cyclooxygenase-2-specific inhibitor indicated to treat acute pain and pain secondary to osteoarthritis and rheumatoid arthritis. Surgical models of acute pain have demonstrated superior pain relief to placebo. The objective of this study was to test the safety and efficacy of celecoxib for pain relief after tonsillectomy compared to placebo. METHODS: Adult subjects were randomized to 200 mg celecoxib versus placebo with a loading dose the night before surgery then twice daily for 10 days. Subjects were instructed to supplement the study drug with hydrocodone/acetaminophen liquid or acetaminophen for pain as needed. Subjects completed a daily diary regarding their pain, nausea, vomiting, diet, and activity. RESULTS: Seventeen subjects enrolled. Intraoperative blood loss was similar between groups, and no subject had postoperative bleeding. Three patients returned to the emergency department for treatment, and 2 patients could not complete the diaries, all in the placebo group. Subjects in the placebo group required statistically significant (P < .05) higher doses of narcotic and acetaminophen to control pain. Pain and diet rating scores were slightly better in the celecoxib group compared to placebo. CONCLUSIONS: In this small cohort, celecoxib reduced postoperative narcotic and acetaminophen requirements compared to placebo without complications. PMID- 27357972 TI - Masticator Space Foreign Body in a Child Presenting With Otorrhea and Granulation Tissue of the External Auditory Canal. AB - OBJECTIVE: We report an unusual case of masticator space foreign body in a patient presenting with otorrhea and granulation tissue within the external auditory canal (EAC). METHODS: Case report. RESULTS: A 16-month-old male presented with fever, unilateral otorrhea, facial swelling, leukocytosis, and granulation tissue within the EAC that failed to respond to conventional medical treatment. Computed tomography scan showed EAC and middle ear opacification and soft tissue swelling involving the masticator space. Given concerns for malignancy, biopsies of tissue within the EAC and of a newly detected right buccal mass were performed, revealing granulation tissue. Concern persisted for neoplasm, however, and magnetic resonance imaging was obtained, showing a masticator space foreign body and possible osteomyelitis of the mandible and pterygoid plates. The patient underwent urgent operative removal of a 3 cm crayon fragment from the masticator space and debridement of granulation tissue arising from a small defect at the inferior medial cartilaginous EAC. He likely sustained foreign body injury several weeks earlier upon falling from standing height while biting a crayon. Postoperatively, he was observed in hospital on intravenous antibiotics and improved significantly. He has since fully recovered. CONCLUSION: Masticator space foreign bodies may present with erosion and granulation tissue of the EAC. PMID- 27357973 TI - Novel Computed Tomography Scoring System for Sinus Disease in Adults With Cystic Fibrosis. AB - OBJECTIVE: There is no easy to use scoring system for computed tomography (CT) scans of the sinuses that is specific to cystic fibrosis (CF). We propose a simple and easily implemented scoring system to quantify severity of sinus disease in adults with CF. STUDY DESIGN: Case series with chart review. SETTING: Academic tertiary-care referral center. SUBJECTS: Sixty-nine adult patients with CF and 50 age-matched controls. METHODS: We validated a scoring system for CF sinus disease. The CT scans were interpreted by 3 physicians on 2 separate sittings. Parameters include maxillary opacification, nasal obstruction, lateral nasal wall displacement, uncinate process absence/demineralization, and presence/absence of mucocele. RESULTS: Patients with CF aged 21 to 30 years (mean = 24.7 +/- 2.49). In CF cohort (n = 69), intrarater reliability for the 10 CT categories ranged from .70 to 1.00. Twenty-six (87%) were in the excellent range, and the remaining 4 (13%) were evaluated as good. In the non-CF cohort (n = 50), reliabilities ranged from .44 to 1.00. Twenty-seven (90%) were in the excellent range. For interrater reliability, in the CF cohort, 10 CT categories across the 3 raters ranged from .55 to 1.00. Excellent reliability was achieved in 15 (50%) of the observations. In the non-CF cohort, reliabilities ranged from .44 to 1.00. CONCLUSION: A novel and easy to use CT scoring system for CF sinus disease in adults was validated with inter- and intrarater reliability. This new CF sinus disease-specific scoring system can be used by clinicians, surgeons, and radiologists. PMID- 27357974 TI - Laryngeal Framework Surgery in the Irradiated Neck: A Retrospective Matched Cohort Study. AB - BACKGROUND: Laryngeal framework surgery (LFS) remains a cornerstone treatment in the management of glottic insufficiency. Traditionally, a history of radiation to the neck has been considered a relative contraindication to LFS. METHODS: A retrospective matched cohort study was performed to study LFS outcomes in patients with and without a history of radiation. Variables studied included radiation specifics, surgical time, operative difficulty, complications, need for revision surgery, and Voice Handicap Index-10 (VHI-10) scores. RESULTS: A total of 298 patients were studied. Fourteen patients with a history of neck irradiation were matched with 14 nonirradiated controls. No complications were encountered in the nonirradiated cohort. In the irradiated cohort, there were 2 minor wound complications and 1 admission for stridor treated medically. No cases of implant extrusion were observed. The VHI-10 scores were improved in both cohorts relative to preoperative baseline (P = .001). Posttreatment VHI-10 scores were better in the nonirradiated cohort (P = .03). There was no difference between cohorts with respect to complication rates, surgical time, surgical difficulty, length of stay, use of a surgical drain, or need for revision surgery. CONCLUSION: Laryngeal framework surgery is safe and associated with improved voice outcomes in patients with a history of neck irradiation. PMID- 27357975 TI - Cortical Auditory Evoked Potentials to Evaluate Cochlear Implant Candidacy in an Ear With Long-standing Hearing Loss: A Case Report. AB - OBJECTIVES: We describe a novel use of cortical auditory evoked potentials in the preoperative workup to determine ear candidacy for cochlear implantation. METHODS: A 71-year-old male was evaluated who had a long-deafened right ear, had never worn a hearing aid in that ear, and relied heavily on use of a left-sided hearing aid. Electroencephalographic testing was performed using free field auditory stimulation of each ear independently with pure tones at 1000 and 2000 Hz at approximately 10 dB above pure-tone thresholds for each frequency and for each ear. RESULTS: Mature cortical potentials were identified through auditory stimulation of the long-deafened ear. The patient underwent successful implantation of that ear. He experienced progressively improving aided pure-tone thresholds and binaural speech recognition benefit (AzBio score of 74%). CONCLUSIONS: Findings suggest that use of cortical auditory evoked potentials may serve a preoperative role in ear selection prior to cochlear implantation. PMID- 27357976 TI - Detection of Enteric Viruses in Fecal Specimens from Nonbacterial Foodborne Gastroenteritis Outbreaks in Tokyo, Japan between 1966 and 1983. AB - We investigated the prevalence of 5 enteric viruses (norovirus [NoV], sapovirus, rotavirus, astrovirus, and adenovirus) in archived stool specimens collected from 70 foodborne gastroenteritis outbreaks in Tokyo, Japan, which occurred from 1966 to 1983, and genetically characterized these viruses. NoV was detected in 48 (68.6%) outbreaks, while SaV, group C rotavirus (RVC), and astrovirus were detected in 1 (1.4%) outbreak each. Based on the partial capsid sequences, the detected NoVs were classified into the following genotypes: 9 in genogroup I (GI; GI.1-6, GI.8, GI.9, and GI.NA), 13 GII (GII.1-9, GII.13, GII.16, GII.17, and GII.22), and one in GIV. The oldest NoV outbreaks occurred in 1966. No predominant genotype was found. One strain, classified as GI. NA based on the N/S region sequence, was subsequently classified as GI.8 based on the complete VP1 sequence. Nine types of recombinant NoV sequences, including 7 unreported combinations, were identified. Further genetic characterization of NoV GII.17 and GII.4 demonstrated that the NoV GII.17 strains detected from 1970 to 1982 clustered independently from previously reported NoV GII.17 strains. Phylogenetic analysis, using the complete VP1 region and the P2 domain, demonstrated that NoV GII.4 strains collected between 1975 and 1980 clustered with archival strains collected in the USA in the mid-1970s. In contrast, a NoV GII.4 strain collected in 1983 formed an independent branch from reference strains collected in the mid 1970s to 2012. PMID- 27357977 TI - The Epidemic of Human Immunodeficiency Virus, Hepatitis C Virus, and Syphilis Infection, and the Correlates of Sexually Transmitted Infections among Men Who Have Sex with Men in Zhenjiang, Jiangsu, China. AB - A cross sectional survey was performed to investigate the epidemic of human immunodeficiency virus (HIV), hepatitis C virus (HCV), syphilis, and HIV-1 subtype infections among men who have sex with men (MSM) and to evaluate factors that were correlated with sexually transmitted infections (STIs) among 657 MSM in Zhenjiang, Jiangsu, during 2012-2013. Data on socio-demographic parameters and risky behaviors were collected, and blood samples were obtained. In this survey, the prevalence of STIs due to HIV (5.3%), HCV (0.6%), and syphilis (19.2%) were measured. Of 35 HIV-infected MSM, 1 (0.2%) and 17 (2.6%) were co-infected with HCV and syphilis. Among 33 samples with available HIV-1 genomic fragment sequences, 6.1% B, 72.7% CRF01_AE, and 21.2% CRF07_BC were identified. Multivariate logistic regression analysis showed that age > 30 years (odds ratio [OR] 2.002; 95% confidence interval [CI], 1.144-3.502) and having had STI symptoms in the past year (OR, 11.673; 95% CI, 3.092-44.078) were positively correlated with having an STI, while consistent use of a condom when having sex with male partners (OR, 0.621; 95% CI, 0.408-0.945) was significantly associated with a low STI rate. The worsening epidemic of HIV, HCV, and syphilis infections, and the prevalence of complex subtypes of HIV-1 and other risk factors suggest that effective intervention strategies should be strengthened for MSM in Zhenjiang, Jiangsu. PMID- 27357978 TI - Immunity to Diphtheria and Tetanus in Army Personnel and Adult Civilians in Mashhad, Iran. AB - This study aimed to investigate serologic immunity to diphtheria and tetanus in army personnel and a sample population of adult civilians in Mashhad, Iran. Army personnel (n = 180) and civilians (n = 83) who presented at Mashhad army hospital participated in this study. Diphtheria and tetanus antitoxin levels were determined by enzyme-linked immunosorbent assay. Approximately 77% and 94% of army personnel aged 18-34 years had at least basic protection against diphtheria (antitoxin level >=0.1 IU/mL) and tetanus (antitoxin level >0.1 IU/mL), respectively. For civilians in this age group, the proportions were 76% for both diseases. Antitoxin levels waned with age. Thus, participants older than 50 years had lower immunity; this decrease in immunity was more pronounced for tetanus than for diphtheria in both army personnel and civilians. For both diseases, geometric mean antitoxin titers and the proportion of participants with at least basic protection were higher in subjects with a history of vaccination in the last 10 years (P < 0.001), higher in men than women, and in army personnel than civilians in each age group. Young army personnel and civilians (18-34 years old) had adequate immunity to diphtheria and tetanus. However, the large number of susceptible older adults (>50 years old) calls for improved booster vaccination protocols. PMID- 27357980 TI - Genetic Analysis of HIV-1 in Japan: a Comprehensive Analysis of Donated Blood. AB - In Japan, the number of human immunodeficiency virus (HIV)-1 infections remains relatively low; nevertheless, the annual incidence of HIV-1 infection has not decreased. New infections remain a great concern, and an improved understanding of epidemiological trends is critical for public health. The env C2V3 and pol sequences of HIV-1 RNA from 240 early (1996-2001) and 223 more recent (2010-2012) blood donations were used to compare the distribution of virus subtypes and to generate phylogenetic trees. Subtype B was clearly predominant in both early and more recent donations (both were 88.3%), and CRF01_AE was the second most common subtype. Phylogenetic analysis revealed a peculiar epidemiological transition. Compared to early subtype B isolates from 2 major endemic areas (Tokyo and Osaka), the more recent subtype B isolates formed fewer tight clusters in phylogenetic trees (from 8 to 2 clusters in Tokyo and 5 to zero clusters in Osaka). Furthermore, mixing of HIV-1 infections between these 2 endemic areas appear to increase. Analysis of phylogenetic trees suggested that local outbreaks have become smaller in Japan; however, intermixing of viral types between these 2 areas was more evident in the more recent samples. PMID- 27357979 TI - HIV Testing in Non-Injection Drug Users: Prevalence and Associated Factors. AB - The objective of this study was to estimate the prevalence of and identify factors associated with lifetime testing for the human immunodeficiency virus (HIV) in non-injection drug users (NIDU). A cross-sectional study was conducted with 323 individuals in clinics for chemical dependency in the state of Goias in the Central-West region of Brazil. Logistic regression analysis was used to identify factors associated with lifetime HIV testing. Testing for HIV was associated with age, female gender, crack use, history of sexually transmitted infections, acquaintance with people living with HIV/AIDS and/or who had died from AIDS, and history of having received some instruction on HIV/AIDS prevention methods. It was found that only 26.6% reported having access to the HIV rapid test. We concluded determinants for HIV testing must be taken into account when planning prevention and programming strategies. These include the widening of testing coverage among NIDU, educational health actions, establishment of links between sexually transmitted infection prevention services and addiction treatment services, and the use of rapid tests to help people who are in contact with the virus learn about their HIV status, enter treatment, and improve their quality of life. PMID- 27357981 TI - Characteristics of Multidrug-Resistant Corynebacterium spp. Isolated from Blood Cultures of Hospitalized Patients in Japan. AB - Corynebacterium is a genus consisting of Gram-positive, rod-shaped bacteria, that is wildly distributed in nature. We report the epidemiological characterization of Corynebacterium spp. isolated from blood specimens at the Kurume University Hospital, between June 2008 and November 2011. Twenty-two strains that were likely Corynebacterium spp. were isolated from 22 hospitalized patients, of which 12 (54.5%) were identified as Corynebacterium striatum. Minimum inhibitory concentration tests were performed after biochemical and genotypic identifications. Biofilm production was detected using a 96-well microplate assay. The dissemination of C. striatum was investigated using pulsed-field gel electrophoresis (PFGE). All strains showed the tendency to be resistant to multiple drugs except vancomycin. Fourteen (82.4%) strains, including 9 C. striatum strains were capable of producing biofilms. Four distinct PFGE patterns were detected among C. striatum strains; 6 of which were identified as dominant pattern A (defined in this study) and had high biofilm production ability. During the 3-year monitoring period, these strains might have repeatedly infected the patients or could have readily colonized the hospital environments. C. striatum appeared to be a potential risk factor for bloodstream infections in hospitalized patients. More surveillance and enhanced control strategies are necessary to decrease Corynebacterium spp. infections in hospitals. PMID- 27357982 TI - Canine Echinococcosis Due to Echinococcus multilocularis: a Second Notifiable Case from Mainland Japan. PMID- 27357983 TI - Development of a Novel Loop-Mediated Isothermal Amplification (LAMP) Assay for the Detection of Rickettsia spp. AB - We developed a novel loop-mediated isothermal amplification (LAMP) method to detect Rickettsia spp., including Rickettsia prowazekii and R. typhi. Species specific LAMP primers were developed for orthologous genes conserved among Rickettsia spp. The selected modified primers could detect all the Rickettsia spp. tested. The LAMP method was successfully used to detect 100 DNA copies of Rickettsia spp. within approximately 60 min at 63C. Therefore, this method may be an excellent tool for the early diagnosis of rickettsiosis in a laboratory or in the field. PMID- 27357984 TI - Histopathological Findings of Lung with A/H1N1pdm09 Infection-Associated Acute Respiratory Distress Syndrome in the Post-Pandemic Season. AB - We herein report the pulmonary histopathological findings of an autopsy case of post-pandemic season A/H1N1pdm09 infection-associated acute respiratory distress syndrome (ARDS). The lung histology predominantly exhibited findings indicative of the exudative phase of diffuse alveolar damage, with similar inflammation severity observed in all sections. Furthermore, the lung sections only showed a few A/H1N1pdm09 antigen-positive cells along with a low viral RNA copy number. The sequence of the viral hemagglutinin receptor binding site identified a preference for alpha-2,6 linked sialic acid, suggesting low alveolar epithelial cell infectivity. The pathological findings, in this case, differed in several aspects from those of the first autopsy case of A/H1N1pdm09 infection-associated ARDS in Japan, reported during the 2009 pandemic season. In conclusion, pathological and molecular biological examinations suggested that in the post pandemic season A/H1N1pdm09 infection, the infection-associated ARDS was not caused by direct infection-induced damage to the alveolar epithelial cells but was rather a result of indirect sepsis-mediated endothelial cell damage. PMID- 27357985 TI - The Prevalence of High Antiretroviral Coverage and Viral Suppression in Japan: an Excellent Profile for a Downstream Human Immunodeficiency Virus Care Spectrum. AB - We investigated the effectiveness of the Japanese health care system for human immunodeficiency virus/acquired immunodeficiency virus (HIV/AIDS), in terms of prevention, diagnosis, access to antiretroviral treatment, and treatment outcomes. Clinical information on HIV/AIDS cases was collected via questionnaires sent to 377 registered HIV/AIDS clinics in Japan. Data on 9,040 and 14,569 cases were collected in 2009 and 2014, respectively. The percentages of cases undergoing treatment were 69.6% and 87.8% in 2009 and 2014, respectively, demonstrating an improvement in treatment coverage over the 5 years between the 2 surveys. The proportion of cases with undetectable HIV RNA in the 2014 survey was 87.7%. Thus, our survey revealed that the 2 of the United Nations AIDS Fast-Track targets, 90% treated and 90% virally suppressed, are close to being achieved. However, Japan appears to have fallen short of the upstream target of 90% diagnosed. Japan needs to radically reform its strategies for encouraging people to undergo HIV testing and to develop a system for estimating the number of people living with HIV. PMID- 27357986 TI - Accuracy of a Stick-Type Kit and Enzyme-Linked Immunosorbent Assay in Detecting Helicobacter pylori Antibodies in Urine of People Living in the Japan Sea Region of Northern Japan. AB - In Japan, both a stick-type kit and an enzyme-linked immunosorbent assay (ELISA) kit are available for the detection of antibodies to Helicobacter pylori in urine. However, the accuracy of these tests has not been fully examined in northern Japanese populations. Urine samples from 359 subjects were tested using a stick-type H. pylori-antibody detection kit (RAPIRUN), and urine samples from 201 subjects were tested using an ELISA-based test (URINELISA). The prevalence of H. pylori infection was determined by the 13C-urea breath test (UBT) and a monoclonal antibody-based stool antigen test (TPAg). Subjects were considered to have the infection if either the UBT or rapid TPAg results were positive. The percentage of positive test results for RAPIRUN and URINELISA was 54.0% and 40.8%, respectively. Sensitivity and specificity were 83.3% and 67.0%, respectively, for RAPIRUN and 86.5% and 85.8% for URINELISA. Nineteen subjects had cut-off index values of between 0.4 and 0.9 by URINELISA, and 4 of these subjects (21.1%) were found to be infected with H. pylori. The urine-based ELISA was more accurate than the rapid stick-type kit in these patients. If negative ELISA results are near the cut-off value, subjects should receive an additional test to determine whether they are infected with H. pylori. PMID- 27357987 TI - The First Case Report of Cerebral Cyst Infection Due to Helicobacter cinaedi. AB - We report the first case of cerebral cyst infection by Helicobacter cinaedi, a fastidious spiral-shaped gram-negative rod bacterium. A 70-year-old man visited Tokyo Medical University Hospital with persisting fever since 2 weeks. He underwent surgery and radiotherapy for parapharyngeal space squamous cell carcinoma 10 years ago. The radiotherapy resulted in a cerebral cyst as a side effect, and an Ommaya reservoir was inserted into the cyst. Blood culture and analysis of the brain cyst fluid revealed the presence of spiral-shaped gram negative rod bacteria, which were identified as H. cinaedi by polymerase chain reaction. Initially, we administered clarithromycin (400 mg per day). After H. cinaedi infection was confirmed, the treatment was changed to meropenem (MEPM 6 g per day). The patient was treated for 43 days in the hospital with intravenous meropenem, and his clinical course was satisfactory. On the 44th day, he was discharged and prescribed oral minocycline (MINO 200 mg per day). After discharge, the patient's H. cinaedi infection did not recur. Our case illustrated the wide clinical spectrum of H. cinaedi as well as the effectiveness of antibiotic therapy comprising MERM and MINO for treating central nervous system infection by this organism. PMID- 27357989 TI - Elevated Serum Levels of Thymic Stromal Lymphopoietin in Wheezing Children Infected with Human Metapneumovirus. AB - Our aim was to study the epidemiology and clinical manifestations of human metapneumovirus (hMPV) infection in children in the Suzhou area, China, and to investigate the effect of thymic stromal lymphopoietin (TSLP) on wheezing in hMPV infected children. The study included 13,533 children with respiratory tract infections who were admitted to the Children's Hospital of Soochow University between January 2009 and December 2014. Clinical data were recorded. Plasma levels of TSLP, interleukin (IL)-4, and IL-2 were compared among 35 wheezing children with single hMPV infection, 15 non-wheezing children with hMPV infection, and 35 wheezing children with other viral infections. The annual rates of hMPV infection from 2009 to 2014 were 2.33%, 6.41%, 3.29%, 3.52%, 0.23%, and 0.64%, respectively, peaking in 2010. The number of CD3-/CD16+/CD56+ cells was significantly lower in inpatients with hMPV infection than that in patients with other viral infections. Serum levels of TSLP and IL-4 in wheezing children with hMPV infection were significantly higher than the levels in the other 2 groups. hMPV is a common viral pathogen that causes respiratory infections in children in Suzhou, but annual rates have declined since 2010. Infection with hMPV may affect cell-mediated immunity. Serum TSLP levels were elevated after hMPV infection. PMID- 27357988 TI - Bacteremia Due to Arthrobacter creatinolyticus in an Elderly Diabetic Man with Acute Cholangitis. AB - An 87-year-old man with poorly controlled diabetic mellitus presented with fever, bedsores, and elevated hepatobiliary enzyme levels. He was diagnosed with bacteremia with acute cholangitis due to Arthrobacter species, which are Gram positive, aerobic, catalase-positive, coryneform bacteria belonging to the family Microbacteriaceae. Doripenem and subsequencial sulbactam/ampicillin treatment were used for the acute cholangitis, and the bacteremia was treated with a 2-week course of vancomycin. The bacteremia was misidentified by the phenotyping assay (API Coryne test), but was identified as Arthrobacter creatinolyticus by 16S rRNA and matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry. To our knowledge, this is the first report of a human case of A. creatinolyticus bacteremia. PMID- 27357990 TI - Regional Variations in the Incidence of Rotavirus Hospitalization in Children Living in Defined Regions of Akita and Kyoto Prefectures, Japan. AB - Variable incidence rates of rotavirus gastroenteritis hospitalizations have been reported in Japan. However, it is not known whether the observed regional differences were due to the real difference in the occurrence of severe disease or other causes. This study aimed to determine the incidence rates of rotavirus hospitalization among children aged <5 years in the Yuri district in Akita prefecture and the Nantan district in Kyoto prefecture between March 2012 and February 2013. During this period, rotavirus vaccine uptake rates were equally low in both regions. All specimens were evaluated using the standardized case definition, severity scores, and the same assays. There were 44 rotavirus cases (44%) among 101 acute gastroenteritis-related hospitalizations in the Yuri district with a catchment population of 3,853, and 18 rotavirus cases (47%) among 38 acute gastroenteritis-related hospitalizations in the Nantan district with a catchment population of 5,128. While the severity score at the time of the hospitalizations was 11 in both hospitals, the incidence rates in Akita and Kyoto were 11.7 (95% confidence interval [CI]: 8.5-15.6) and 3.9 (95% CI: 2.1-5.5) per 1,000 child-years, respectively. Thus, there was a real difference in the occurrence rate of severe rotavirus infections between the 2 regions. PMID- 27357991 TI - Immune Response to the Mumps Virus in Iranian Unvaccinated Young Adults. AB - Although the first mumps vaccine was licensed more than 50 years ago, the vaccine was added to Iran's Expanded Program on Immunization in 2003. Therefore, the majority of Iranians born before 2003 are unvaccinated, and their immunity is the result of natural infection. In order to evaluate cellular responses against the mumps virus following natural infection, we investigated 90 Iranian unvaccinated adults aged 20-30 years. Mumps specific memory CD4+ and CD8+ proliferation and frequency of cytotoxic lymphocyte CD8+ CD107a were evaluated using flow cytometry. Our results showed that 33 subjects were seronegative, but 28 of them showed degranulation of CD8+ T lymphocytes and expression of CD 107a, as well as proliferation of CD4 and CD8 T cells, in response to mumps antigen stimulation. In all seropositive subjects, degranulation of cytotoxic T lymphocytes and proliferation of CD4+ and CD8+ T lymphocytes was detected. Proliferation of T cells and degranulation of CD8 T cells in seropositive subjects was higher than in seronegative subjects. We conclude that natural mumps infection and subclinical reinfection could induce good protection, but the severe complications associated with mumps infections suggest the need for mumps vaccination. Natural boosters because of the prevalence of the wild-type virus may help with maintenance of immunity in populations with high vaccine coverage. PMID- 27357992 TI - HeLa-ACE2-TMPRSS2 Cells Are Useful for the Isolation of Human Coronavirus 229E. PMID- 27357993 TI - A Case of Scrub Typhus Imported from South Korea to Yamagata, Japan. PMID- 27357994 TI - Co-Colonization with Neisseria species Is a Risk Factor for Prolonged Colonization with Multidrug-Resistant Acinetobacter baumannii in the Respiratory Tract. AB - Multidrug-resistant Acinetobacter baumannii (MDRAB) colonization increases the risk of bacterial spread in the hospital setting. The impact of clinical factors, including antibiotic use, on prolongation of MDRAB colonization has not been investigated. Patients with respiratory tract MDRAB detected using culture were enrolled in this study. Long-term colonizers and short-term colonizers were defined as patients whose colonization periods were >30 days or <=30 days, respectively. Clinical data were abstracted from medical records. MDRAB was isolated in 34 patients. There were 13 long-term colonizers and 9 short-term colonizers. Twelve patients were lost to follow-up and excluded from the study. There were no significant differences in average leukocyte counts, numbers of antibiotic classes administered, duration of antibiotic use in the 30 days following colonization, or rates of central catheterization or mechanical ventilation between the 2 groups. Long-term colonizers carried Neisseria species (spp.) more frequently in the 30 days following colonization than short-term colonizers (7/13 vs 1/9, p = 0.01); however, this was not the case prior to colonization with MDRAB (5/13 vs 1/9, p = 0.33). The 90-day MDRAB colonization rates for Neisseria-negative patients and Neisseria-positive patients were 10.0% and 83.3%, respectively (P < 0.01). Prolonged MDRAB colonization in the respiratory tract was associated with Neisseria spp. co-colonization. PMID- 27357995 TI - Novel Isolation of Mycoplasma amphoriforme from a Pediatric Patient with Protracted Bronchitis in Japan. PMID- 27357996 TI - Sleep problems, anxiety, depression and fatigue on family members of adult intensive care unit patients. AB - The purpose of this study was to determine the levels of sleep problems, anxiety, depression and fatigue in family members of intensive care patients in Turkey and factors affecting these complaints. This cross-sectional study was carried out with 350 first-degree relatives of intensive care patients at a university and state hospital. Data were collected between 5 January and 30 May 2014 using a personal information form, the Visual Analogue Scale for Fatigue, the Hospital Anxiety and Depression Scale and the modified Post Sleep Inventory. Of the 350 family members, 76% reported moderate or more serious problems. Anxiety was reported by 81.4% of the family members, and depression by 94.2%. Family members in the study had fatigue, with average scores of 79.42. There were significant correlations between the Visual Analogue Scale for Fatigue and anxiety, depression and scores on the Modified Post-Sleep Inventory (P < 0.05). Family members of intensive care patients experienced symptoms of fatigue, anxiety, depression and sleep problems. The prevalence of symptoms of sleep problems, anxiety and depression and complaints of fatigue was significantly higher in the family members of intensive care patients in Turkey than reported in the literature. PMID- 27357997 TI - Ventriculomegaly in very-low-birthweight infants with Down syndrome. AB - AIM: The prevalence of Down syndrome in infants with fetal ventriculomegaly is 5% to 10%; however, the converse, the prevalence of cerebral ventriculomegaly in live-born infants with Down syndrome, is not well established. Because cranial ultrasounds are performed on most very-low-birthweight (VLBW) infants (birthweight <1500g), our aim was to examine ultrasound abnormalities of VLBW infants to determine prevalence of ventriculomegaly and intraventricular hemorrhage (IVH) in VLBW infants with Down syndrome, and whether VLBW infants with Down syndrome are at higher risk for cranial ultrasound abnormalities, compared with the already elevated risk in other VLBW infants. METHOD: This study comprised retrospective analysis of data from Pediatrix BabySteps Clinical Data Warehouse. The study population consisted of 121 736 VLBW infants (61 869 males, 59 867 females), born between 1996 and 2013, of whom 441 had Down syndrome (233 males, 208 females; mean gestational age 30wks, standard deviation [SD] 2.8wks). Logistic regression was used to calculate odds of ventriculomegaly and IVH for Down syndrome. RESULTS: Prevalence of ventriculomegaly in Down syndrome was 5.2% compared with 0.8% in other VLBW infants. Multivariate analysis indicated 5.8* odds (95% confidence interval [CI] 3.4-9.7) of ventriculomegaly in Down syndrome and 0.9* odds (95% CI 0.7-1.1) of IVH for Down syndrome. INTERPRETATION: Very preterm infants with Down syndrome are at increased risk for ventriculomegaly (but not for IVH) compared with other infants born very preterm. PMID- 27357998 TI - A Registry for Evaluation of Efficiency and Safety of Surgical Treatment of Cartilage Defects: The German Cartilage Registry (KnorpelRegister DGOU). AB - BACKGROUND: The need for documentation in cartilage defects is as obvious as in other medical specialties. Cartilage defects can cause significant pain, and lead to reduced quality of life and loss of function of the affected joint. The risk of developing osteoarthritis is high. Therefore, the socioeconomic burden of cartilage defects should not be underestimated. OBJECTIVE: The objective of our study was to implement and maintain a registry of all patients undergoing surgical treatment of cartilage defects. METHODS: We designed this multicenter registry for adults whose cartilage defects of a knee, ankle, or hip joint are treated surgically. The registry consists of two parts: one for the physician and one for the patient. Data for both parts will be gathered at baseline and at 6-, 12-, 24-, 36-, 60-, and 120-month follow-ups. RESULTS: To date, a wide range of German, Swiss, and Austrian trial sites are taking part in the German Cartilage Registry, soon to be followed by further sites. More than 2124 (as of January 31, 2016) cases are already documented and the first publications have been released. CONCLUSIONS: The German Cartilage Registry addresses fundamental issues regarding the current medical care situation of patients with cartilage defects of knee, ankle, and hip joints. In addition, the registry will help to identify various procedure-specific complications, along with putative advantages and disadvantages of different chondrocyte products. It provides an expanding large scale, unselected, standardized database for cost and care research for further retrospective studies. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00005617; https://drks-neu.uniklinik-freiburg.de/ drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00005617 (Archived by WebCite at http://www.webcitation.org/6hbFqSws0). PMID- 27357999 TI - Abeta-Immunotherapeutic strategies: a wide range of approaches for Alzheimer's disease treatment. AB - Current therapies to treat Alzheimer's disease (AD) are focused on ameliorating symptoms instead of treating the underlying causes of AD. The accumulation of amyloid beta (Abeta) oligomers, whether by an increase in production or by a decrease in clearance, has been described as the seed that initiates the pathological cascade in AD. Developing therapies to target these species is a vital step in improving AD treatment. Abeta-immunotherapy, especially passive immunotherapy, is a promising approach to reduce the Abeta burden. Up to now, several monoclonal antibodies (mAbs) have been tested in clinical trials on humans, but none of them have passed Phase III. In all likelihood, these trials failed mainly because patients with mild-to-moderate AD were recruited, and thus treatment may have been too late to be effective. Therefore, many ongoing clinical trials are being conducted in patients at the prodromal stage. New structures based on antibody fragments have been engineered intending to improve efficacy and safety. This review presents the properties of this variety of developing treatments and provides a perspective on state-of-the-art of passive Abeta-immunotherapy in AD. PMID- 27358000 TI - Eigenspectra optoacoustic tomography achieves quantitative blood oxygenation imaging deep in tissues. AB - Light propagating in tissue attains a spectrum that varies with location due to wavelength-dependent fluence attenuation, an effect that causes spectral corruption. Spectral corruption has limited the quantification accuracy of optical and optoacoustic spectroscopic methods, and impeded the goal of imaging blood oxygen saturation (sO2) deep in tissues; a critical goal for the assessment of oxygenation in physiological processes and disease. Here we describe light fluence in the spectral domain and introduce eigenspectra multispectral optoacoustic tomography (eMSOT) to account for wavelength-dependent light attenuation, and estimate blood sO2 within deep tissue. We validate eMSOT in simulations, phantoms and animal measurements and spatially resolve sO2 in muscle and tumours, validating our measurements with histology data. eMSOT shows substantial sO2 accuracy enhancement over previous optoacoustic methods, potentially serving as a valuable tool for imaging tissue pathophysiology. PMID- 27358001 TI - IL-33/ST2 pathway in a bleomycin-induced pulmonary fibrosis model. AB - The present study aimed to investigate the interleukin (IL)-33/ST2 pathway in a model of acute pulmonary fibrosis, and to examine the pathogenesis of pulmonary fibrosis. The pulmonary fibrosis model was established by a single exposure to bleomycin (BLM group) endotracheally to represent idiopathic pulmonary fibrosis, and a control (Cont) group was treated with the same volume of saline. The degrees of acute injury, inflammation and fibrosis were detected using hematoxylin and eosin and Masson's staining. The IL-33, ST2, myeloid differentiation primary response 88 (MyD88) and tumor necrosis factor receptor associated factor 6 (TRAF6) proteins were detected using Western blotting. The serum levels of IL-4 and IL-13 were detected using an enzyme-linked immunosorbent assay. The results indicated that, compared with the Cont group, there were significant differences in the alveolitis scores in the BLM group on days 3, 7, 14 and 28 (P<0.01). The grades of fibrosis were also significantly different on days 7, 14 and 28 (P<0.01). On examining the dynamic protein expression levels of IL-33, ST2, MyD88 and TRAF6, the expression of IL-33 in the BLM group increased initially, and then decreased gradually following a peak on day 7. The significant differences between the BLM and Cont groups were observed on days 3 and 7 (P<0.05). Compared with the Cont group, the protein levels of ST2, MyD88 and TRAF6 in the BLM group exhibited an increasing trend from day 3, with significant differences, compared with the Cont group, on days 3, 7, 14 and 28 (P<0.05). On examination of the serum levels of IL-4 and IL-13 in each group, the levels of IL-4 and IL-13 in BLM group remained higher from day 7, with peaks on day 28, and were significantly different, compared with the Cont group, on days 7, 14 and 28 (P<0.05). In conclusion, the IL-33/ST2 signaling pathway was found to be involved in the rodent model of pulmonary fibrosis induced by bleomycin. PMID- 27358002 TI - [Not Available]. PMID- 27358003 TI - [Functional genioplasty in growing patients]. AB - Objective - To evaluate the role of age as a moderator of bone regeneration patterns and symphysis remodeling after genioplasty. Method - Fifty-four patients who underwent genioplasty at the end of their orthodontic treatment were divided into three age groups: younger than 15 years at the time of surgery (group 1), 15 to 19 years (group 2), and 20 years or older (group 3). Twenty-three patients who did not accept genioplasty and had a follow-up radiograph two years after the end of their orthodontic treatment were used as a control group. Patients were evaluated at three time points: immediate preoperative (T1), immediate postoperative (T2) and two years postsurgery (T3). Results - The mean genial advancement at surgery was similar for the three age groups, but the extent of remodeling around the repositioned chin was greater in group 1, less in group 2, and still less in group 3. Symphysis thickness increased significantly during the two-years postsurgery interval for the three groups, and this increase was significantly greater in group 1 than in group 3. Remodeling above and behind the repositioned chin also was greater in the younger patients. This was related to greater vertical growth of the dentoalveolar process in the younger patients. There was no evidence of a deleterious effect on mandibular growth. Conclusion - The outcomes of forward-upward genioplasty include increased symphysis thickness, bone apposition above B point, and remodeling at the inferior border. When indications for this type of genioplasty are recognized, early surgical correction (before age 15) produces a better outcome in terms of bone remodeling. PMID- 27358004 TI - [Not Available]. PMID- 27358005 TI - [Aesthetic success in genioplasties procedures criteria]. AB - Maxillomandibular dysmorphia may be associated with structural chin pathologies. Three-dimensional jaws displacements have limits. Specific genioplasty is an additional surgical mean for soft tissues profile normalization. Osteotomy line is examined according an incline angle and a possible lateral extension, as chin wing technique, improves facial shape. Cephalometric set-up with R line analyzes surgical chin movements and impact of lower incisors labial inclination on lower lip and mentolabial fold after advancement genioplasty. Micro-implant anchorage is a precious help to find lower incisors good position and optimum lower occlusal plane frontal shift in asymmetric facial pattern. Orthodontics criteria are essential factors to access an aesthetic success in genioplasties procedures. PMID- 27358007 TI - [Indirect usage of miniscrew anchorage to intrude overerupted mandibular incisors in a Class II patient with a deep overbite]. AB - Vertical dentoalveolar discrepancies are a common problem in orthodontic patients but are often difficult to treat with traditional mechanics. This case report illustrates the successful treatment of overerupted mandibular incisors via the indirect use of miniscrew anchorage. A woman (age, 22 years 9 months) had chief complaints of maxillary incisor protrusion and crooked teeth. An excessive curve of Spee caused by elongation of the mandibular incisors was also found. The patient was diagnosed with a severe Class II Division 1 malocclusion and a deep overbite. After extraction of the mandibular first premolars and the subsequent leveling phase, the elongated incisors were intruded with a novel method, which involved the combined use of sectional archwires and miniscrews placed in the premolar areas. After the procedure, the mandibular incisors had been intruded by 6.5 mm with no undesirable side effects. The total active treatment period was 42 months. The resultant occlusion and satisfactory facial profile were maintained after 30 months of retention. Our novel intrusion approach shows potential for correcting a deep overbite. PMID- 27358006 TI - [Limiting factors in the class III camouflage treatment: a potential protocol]. AB - The Class III skeletal malocclusion has been traditionally treated with a combined approach of orthodontics and orthognathic surgery or with a strategy of orthodontic camouflage. Some severe cases can be identified as ideal candidates for a surgical treatment whereas some others can be handled with orthodontics alone, with a reasonable expectation of an acceptable result. However, the problem remains for the borderline patient. In fact, limited information is available in the literature regarding the identification of the factors that can help in establishing the limits for one treatment modality or the other. Furthermore, the quantification of some of these factors, for practical purposes, is practically missing or very seldom suggested. Therefore, the decision making process remains a subjective reflection based on the "good clinical sense" of the orthodontist or just reduced to an "educated guess". In order to add some information, hopefully useful in deciding the most suitable treatment option for the individual patient, we propose a clinical protocol based on four different factors. Namely: the skeletal discrepancy, the occlusal discrepancy, the periodontal condition and facial aesthetics. For each one of these factors several parameters will be evaluated and, for some of them, an attempt to provide some reference numerical values will be made. Finally, clinical examples will be presented to illustrate the concepts discussed and the treatment alternatives, final treatment plan and treatment outcome will be analyzed for each one of them. PMID- 27358008 TI - Ceramide synthase 4 is highly expressed in involved skin of patients with atopic dermatitis. AB - BACKGROUND: Ceramide is a crucial lipid in the stratum corneum (SC) which maintains the barrier function and hydration of the skin. In atopic dermatitis (AD) patients who have defective skin barrier function, ceramide levels are altered. We previously reported that although the amount of total ceramide was lower in involved skin compared with uninvolved skin of AD patients and with healthy control skin, the amounts of smaller ceramide species of Cer[NS] (<40 total carbons, which are total carbons of both sphingoid base and amide-linked fatty acid), especially Cer[NS] with 34 total carbons (C34-Cer[NS]), were higher. However, the enzyme(s) that produces the higher levels of smaller ceramide species in involved skin of AD patients was unclear. OBJECTIVE: To identify the enzyme(s) that produces higher levels of smaller ceramide species of Cer[NS] in the involved skin of AD patients. METHODS: Eight female Caucasian subjects who were diagnosed with AD on their arms (age range: 21-45 years) were enroled in this study. We compared ceramide levels in the SC and the expression levels of enzymes involved in ceramide metabolism using real-time PCR and immunohistochemistry between involved and uninvolved skin of AD patients. RESULTS: Level of mRNA encoding ceramide synthase 4 (CERS4), which is one of the enzymes that synthesize ceramide from a sphingoid base and an amide-linked fatty acid, was significantly higher in involved skin than in uninvolved skin (P < 0.01). Additionally, the protein expression level of CERS4 in the epidermis was also higher in involved skin compared with uninvolved skin. The expression level of CERS4 correlated with the amount of C34-Cer[NS] (P < 0.01) and the skin hydration value (P < 0.05). CONCLUSIONS: The elevated expression level of CERS4 contributes to the increase of C34-Cer[NS] and the impaired SC barrier function in involved skin of AD patients. PMID- 27358010 TI - Production of monodisperse silica gel microspheres for bioencapsulation by extrusion into an oil cross-flow. AB - Silica gel microspheres are ideal materials for bioencapsulation due to their mechanical properties, biocompatibility, and stability. Encapsulated cells are isolated from the environment and protected from predators, changes in pH, and osmotic stress. However methods for the production of silica gel microspheres suitable for bioencapsulation are not well established. This paper describes a method for the production of monodisperse silicon alkoxide cross-linked silica nanoparticle (SNP) gel microspheres for bioencapsulation in which silica gel precursor is extruded from a needle into a cross-flowing stream of mineral oil. Microspheres produced ranged from 1.3 to 2.9 mm in diameter with coefficients of variation ranging from 2 to 6%. Microsphere size was mainly controlled by the flowrate of the cross-flowing oil and smaller microspheres generally had larger coefficients of variation. The method described in this paper can be optimised to produce silica gel microspheres with a diverse range of compositions and properties. PMID- 27358009 TI - The role of AHR-inducible cytochrome P450s in metabolism of polyunsaturated fatty acids. AB - The environmental pollutant 2,3,7,8-tetrachlorodibenzo-rho-dioxin (TCDD) is the prototype of a large number of non-genotoxic carcinogens, dietary phytochemicals and endogenous metabolites that act via binding the aryl hydrocarbon receptor (AHR). The TCDD-liganded AHR massively upregulates CYP1A1, CYP1A2 and CYP1B1 in many mammalian organs. We demonstrated that TCDD treatment markedly increases the levels of several epoxides and diol metabolites of the epoxides of both omega-6 and omega-3 polyunsaturated fatty acids (PUFA) in the liver and lungs of mice, in an aryl hydrocarbon receptor-dependent fashion, and most likely via the activities of the CYP1 family members. omega-6 Epoxides are known to stimulate tumor growth, angiogenesis, and metastasis in mice. Interestingly, omega-3 epoxides have the opposite effect on these parameters. TCDD and other AHR agonists may, therefore, impact angiogenesis, growth and metastasis of tumors in either a positive or negative way, depending on the relative levels of omega -6 epoxides and omega-3 epoxides generated in the host and/or tumor cells. This is of potential relevance to carcinogenesis by AHR agonists in the human, since the human population is exposed to widely varying omega-6: omega-3 PUFA ratios in the diet. PMID- 27358013 TI - From the Editors. PMID- 27358012 TI - Respiratory syncytial virus subtype ON1/NA1/BA9 predominates in hospitalized children with lower respiratory tract infections. AB - Respiratory syncytial virus (RSV) infection is the leading cause of acute respiratory tract disease in children less than 5 years old. The aim of this study was to further elucidate the molecular properties and clinical characteristics of RSV infection. The study sample included 238 patients <5 years old who were hospitalized with clinical symptoms of upper or lower respiratory tract infection (URTI or LRTI) in the Pediatric Department at the First People's Hospital of Chenzhou, South China in 2014. We subjected nasopharyngeal aspirate (NPA) or nasal swab (NS) samples from the patients to indirect fluorescence assay screens. RSV G genes were amplified by reverse transcription-PCR (RT-PCR) and sequenced. Of the 238 patients screened, 64 (26.8%) were confirmed to have RSV infections. Of those 64 confirmed RSV infection cases, 39 (60.9%) had subtype BA9, 13 (20.3%) had the recently identified subtype ON1, 11 (17.2%) had subtype NA1, and 1 (1.6%) had subtype GB2. The predominant presentation was LRTI with coughing, sputum production, fever, and wheezing. RSV subtype NA1 and BA9 infections were found mostly in infants, whereas the age distribution of subtype ON1 infections was more uniform across the age bands. Phylogenetic analysis indicated that, compared with the prototype strain A2, all ON1 and most NA1 isolates had lost one potential N-glycosylation site at amino acid 251 and 249 due to T251K and N249Y substitution, respectively. These findings suggest that NA1, BA9, and ON1 are the dominant RSV subtypes causing respiratory tract infections in young children presenting to the hospital in South China. J. Med. Virol. 89:213-221, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27358014 TI - Negotiating Pharmaceutical Prices: A Change in Chinese Health Policy. AB - Like many other nations, China believed the key to restricting national health expenditures for pharmaceuticals was the use of governmentally imposed price caps. Given the recent growth in pharmaceutical expenditures, China is moving away from price caps to a new process that includes locally negotiated prices in the hope that such price competition will lower national pharmaceutical pricing. The success of this policy endeavour will depend significantly on managing other aspects of pharmaceutical purchasing. PMID- 27358011 TI - CRISPR-Mediated VHL Knockout Generates an Improved Model for Metastatic Renal Cell Carcinoma. AB - Metastatic renal cell carcinoma (mRCC) is nearly incurable and accounts for most of the mortality associated with RCC. Von Hippel Lindau (VHL) is a tumour suppressor that is lost in the majority of clear cell RCC (ccRCC) cases. Its role in regulating hypoxia-inducible factors-1alpha (HIF-1alpha) and -2alpha (HIF 2alpha) is well-studied. Recent work has demonstrated that VHL knock down induces an epithelial-mesenchymal transition (EMT) phenotype. In this study we showed that a CRISPR/Cas9-mediated knock out of VHL in the RENCA model leads to morphologic and molecular changes indicative of EMT, which in turn drives increased metastasis to the lungs. RENCA cells deficient in HIF-1alpha failed to undergo EMT changes upon VHL knockout. RNA-seq revealed several HIF-1alpha regulated genes that are upregulated in our VHL knockout cells and whose overexpression signifies an aggressive form of ccRCC in the cancer genome atlas (TCGA) database. Independent validation in a new clinical dataset confirms the upregulation of these genes in ccRCC samples compared to adjacent normal tissue. Our findings indicate that loss of VHL could be driving tumour cell dissemination through stabilization of HIF-1alpha in RCC. A better understanding of the mechanisms involved in this phenomenon can guide the search for more effective treatments to combat mRCC. PMID- 27358015 TI - Relative and Global Health: A Comparative Study between Healthcare Systems of Jordan and France. AB - OBJECTIVE: This relative study includes categorical exploration of the economics, demographic, political, social and financial data to realize the basic reasons of the present healthcare systems in these countries. METHODS: Descriptive and comparative methods were used. This study tries to relate the healthcare systems of Jordan with that of France to produce effective lessons that can be helpful for guiding future developments down the correct path. RESULTS: Depending on many factors such as life expectancy, the mortality rate in infants, universal medical coverage and availability of healthcare services to the masses, significant disparities between the two systems were found. CONCLUSION: Through this study, it has been concluded that the healthcare system of Jordan has a lot to improve with regard to standards of services offered, and there are many aspects to be learned from the French healthcare system by the Jordanian one, including the healthcare coverage system and the cost-sharing strategies. PMID- 27358016 TI - Reducing the Impact of Attacks against Healthcare by Curbing the Use of Explosive Weapons in Populated Areas: Developments at the Global Level. AB - Attacks against healthcare in situations of armed conflict have emerged as an issue of increasing concern with explosive weapons - such as aircraft bombs, mortars and improvised explosive devices - accounting for more deaths, injuries and damage than any other type of weapon in attacks on healthcare facilities. While this is perhaps unsurprising, it offers some insight into a possible course of action for dealing with the problem of attacks against healthcare - by curbing the use of explosive weapons in populated areas. There has been growing recognition in recent years of the humanitarian problems caused by the use of such weapons in populated areas. Steps are now being taken at the global level to curb this use which could, in time, make an important contribution to reducing the incidence and devastating impact of attacks against healthcare. PMID- 27358018 TI - To Stay or Go? The Complexities of Providing Healthcare in Insecure Environments. PMID- 27358017 TI - Strategic Documentation of Violence against Healthcare: Towards a Methodology for Accountability. AB - The valuable efforts that have arisen in recent years to document attacks against healthcare workers and infrastructure during armed conflicts have brought this issue to the forefront of the policy agendas of many health, public health, humanitarian and human rights organizations. However, although professionals and activists have highlighted the importance of accountability in deterring these attacks, considerations of international criminal responsibility in data gathering efforts remain underexplored. This paper suggests an approach that could direct further accountability efforts for organizations interested in engaging in documentation. Such non-governmental organizations should aim to gather not only information about the nature of the attack but also data that help establish specific characteristics about the victim, the intent of the attacker and the patterns of violence. Additionally, these efforts to document attacks on healthcare workers, facilities and patients should involve a systematic, rigorous and demonstrable methodology. PMID- 27358019 TI - The effect of dietary changes on distinct components of the metabolic syndrome in a young Sri Lankan population at high risk of CVD. AB - South Asian populations are predisposed to early onset of the metabolic syndrome. Lifestyle intervention programmes have demonstrated a reduction in the metabolic syndrome and CVD risk; however, the most effective components of the multi faceted lifestyle interventions are unknown. We studied 2637 Sri Lankan males (n 1237) and females (n 1380), with a mean BMI of 23.9 (sd 4.2) kg/m2, aged 22.5 (sd 10.0) years, who had participated in a 5-year lifestyle-modification programme to examine the effect of dietary changes on distinct components of the metabolic syndrome. The dietary intervention comprised advice to replace polished starches with unpolished starches, high-fat meat and dairy products with low-fat products and high-sugar beverages and snacks with low-sugar varieties. For the purposes of this analysis, data from the control and intensive lifestyle groups were combined. Anthropometric and biochemical data were recorded, and a FFQ was completed annually. Multiple regression was used to determine the effect of the dietary changes on distinct components of the metabolic syndrome. The ratio unpolished:polished rice was inversely related to change in fasting glucose (beta=-0.084, P=0.007) and TAG (beta=-0.084, P=0.005) and positively associated with change in HDL-cholesterol (beta=0.066, P=0.031) at the 5-year follow-up after controlling for relevant confounders. Red meat intake was positively associated with fasting glucose concentrations (beta=0.05, P=0.017), whereas low fat (beta=-0.046, P=0.018) but not high-fat dairy products (beta=0.003, P=0.853) was inversely related to glucose tolerance at the follow-up visit. Replacement of polished with unpolished rice may be a particularly effective dietary advice in this and similar populations. PMID- 27358020 TI - Melonoside A: An omega-Glycosylated Fatty Acid Amide from the Far Eastern Marine Sponge Melonanchora kobjakovae. AB - Melonoside A (1), the first representative of a new class of omega-glycosylated fatty acid amides, was isolated from the Far Eastern marine sponge Melonanchora kobjakovae. The structure of 1, including absolute configuration, was established using detailed analysis of 1D and 2D NMR, CD, and mass spectra as well as chemical transformations. Compound 1 induces autophagy of human cisplatin resistant germinal tumor cells NCCIT-R. PMID- 27358021 TI - Rebuttal from Craig L. Phillips, Camilla M. Hoyos, Brendon J. Yee and Ronald R. Grunstein. PMID- 27358022 TI - Polymer Capsules for Plaque-Targeted In Vivo Delivery. AB - Targeted polymer capsules can selectively bind to unstable plaques in mice after intravenous injection. Different formulations of the capsules are explored with a synthetic/biopolymer hybrid capsule showing the best stability and small-molecule drug retention. The synthetic polymer is composed of pH-sensitive blocks (PDPA), low-binding blocks (PEG), and click-groups for postfunctionalization with targeting peptides specific to plaques. PMID- 27358023 TI - A HIV-Tat/C4-binding protein chimera encoded by a DNA vaccine is highly immunogenic and contains acute EcoHIV infection in mice. AB - DNA vaccines are cost-effective to manufacture on a global scale and Tat-based DNA vaccines have yielded protective outcomes in preclinical and clinical models of human immunodeficiency virus (HIV), highlighting the potential of such vaccines. However, Tat-based DNA vaccines have been poorly immunogenic, and despite the administration of multiple doses and/or the addition of adjuvants, these vaccines are not in general use. In this study, we improved Tat immunogenicity by fusing it with the oligomerisation domain of a chimeric C4 binding protein (C4b-p), termed IMX313, resulting in Tat heptamerisation and linked Tat to the leader sequence of tissue plasminogen activator (TPA) to ensure that the bulk of heptamerised Tat is secreted. Mice vaccinated with secreted Tat fused to IMX313 (pVAX-sTat-IMX313) developed higher titres of Tat-specific serum IgG, mucosal sIgA and cell-mediated immune (CMI) responses, and showed superior control of EcoHIV infection, a surrogate murine HIV challenge model, compared with animals vaccinated with other test vaccines. Given the crucial contribution of Tat to HIV-1 pathogenesis and the precedent of Tat-based DNA vaccines in conferring some level of protection in animal models, we believe that the virologic control demonstrated with this novel multimerised Tat vaccine highlights the promise of this vaccine candidate for humans. PMID- 27358024 TI - The synchronization of neuronal oscillators determined by the directed network structure of the suprachiasmatic nucleus under different photoperiods. AB - The main function of the principal clock located in the suprachiasmatic nucleus (SCN) of mammals is synchronizing the body rhythms to the 24 h light-dark cycle. Additionally, the SCN is able to adapt to the photoperiod of the cycle which varies among seasons. Under the long photoperiod (LP), the synchronization degree of the SCN neurons is lower than that under the photoperiod (SP). In the present study, a potential explanation is given for this phenomenon. We propose that the asymmetrical coupling between the light-signal-sensitive part (the ventralateral part, abbreviation: VL) and the light-signal-insensitive part (the dorsalmedial part, abbreviation: DM) of the SCN plays a role in the synchronization degree, which is reflected by the ratio of the number of the directed links from the VL neurons to the DM neurons to the total links of both directions between the VL and the DM. The ratio is assumed to characterize the directed network structure under different photoperiods, which is larger under the SP and smaller under the LP. We found that with the larger ratio in the situation of the SP, the synchronization degree is higher. Our finding may shed new light on the asymmetrical coupling between the VL and the DM, and the network structure of the SCN. PMID- 27358025 TI - Photocatalytic oxidation of alkenes and alcohols in water by a manganese(v) nitrido complex. AB - Mn(v) nitrido complex [Mn(N)(CN)4](2-) is an efficient catalyst for visible-light induced oxidation of alkenes and alcohols in water using [Ru(bpy)3](2+) as a photosensitizer and [Co(NH3)5Cl](2+) as a sacrificial oxidant. Alkenes are oxidized to epoxides and alcohols to carbonyl compounds. PMID- 27358027 TI - Angiotensin II type 2 receptor (AT2R) in renal and cardiovascular disease. AB - Angiotensin II (Ang II) is well-considered to be the principal effector of the renin-angiotensin system (RAS), which binds with strong affinity to the angiotensin II type 1 (AT1R) and type 2 (AT2R) receptor subtype. However, activation of both receptors is likely to stimulate different signalling mechanisms/pathways and produce distinct biological responses. The haemodynamic and non-haemodynamic effects of Ang II, including its ability to regulate blood pressure, maintain water-electrolyte balance and promote vasoconstriction and cellular growth are well-documented to be mediated primarily by the AT1R. However, its biological and functional effects mediated through the AT2R subtype are still poorly understood. Recent studies have emphasized that activation of the AT2R regulates tissue and organ development and provides in certain context a potential counter-regulatory mechanism against AT1R-mediated actions. Thus, this review will focus on providing insights into the biological role of the AT2R, in particular its actions within the renal and cardiovascular system. PMID- 27358029 TI - Tryptophan and kynurenines: continuing to court controversy. AB - The role of the amino acid tryptophan in the generation of 5-hydroxy-tryptamine (5-HT) has been expanded over the past 30 years with recognition that its oxidation by indoleamine-2,3-dioxygenase (IDO) results in the formation of kynurenine and metabolites which regulate neuronal excitability, psychiatric status, immune cell activity and balance, and probably implantation and the development of embryos. While the amount of work on this kynurenine pathway continues to accelerate, it is important that disagreements about results, differences of interpretation or problems with technical issues are presented openly and discussed thoroughly so that new research is not mis-led in ways that could have been foreseen. In this issue of Clinical Science, Badawy et al. discuss in depth two opposing views of how changes in tryptophan availability or utilisation bring about their effects on cell function. The original concept that local depletion of tryptophan is responsible seems to be less attractive than the view that kynurenine and its metabolites have direct, potent actions on cells. This conclusion not only clarifies our understanding of the importance of tryptophan metabolism to kynurenine but also raises the possibility that the actions of those metabolites could be novel targets for the development of agonists and antagonists with a range of medical implications. PMID- 27358028 TI - The end of the road for the tryptophan depletion concept in pregnancy and infection. AB - We hypothesize that: (1) L-tryptophan (Trp) is greatly utilized and not depleted in pregnancy; (2) fetal tolerance is achieved in part through immunosuppressive kynurenine (Kyn) metabolites produced by the flux of plasma free (non-albumin bound) Trp down the Kyn pathway; (3) the role of indoleamine 2,3-dioxygenase (IDO) in infection is not related to limitation of an essential amino acid, but is rather associated with stress responses and the production of Kyn metabolites that regulate the activities of antigen presenting cells and T-cells, as well as increased NAD(+) synthesis in IDO-expressing cells; (4) Trp depletion is not a host defence mechanism, but is a consequence of Trp utilization. We recommend that future studies in normal and abnormal pregnancies and in patients with infections or cancer should include measurements of plasma free Trp, determinants of Trp binding (albumin and non-esterified fatty acids), total Trp, determinants of activities of the Trp-degrading enzymes Trp 2,3-dioxygenase (TDO) (cortisol) and IDO (cytokines) and levels of Kyn metabolites. We also hypothesize that abnormal pregnancies and failure to combat infections or cancer may be associated with excessive Trp metabolism that can lead to pathological immunosuppression by excessive production of Kyn metabolites. Mounting evidence from many laboratories indicates that Trp metabolites are key regulators of immune cell behaviour, whereas Trp depletion is an indicator of extensive utilization of this key amino acid. PMID- 27358030 TI - Insulin Therapy Improves Adeno-Associated Virus Transduction of Liver and Skeletal Muscle in Mice and Cultured Cells. AB - Adeno-associated virus (AAV) gene transfer is a promising treatment for genetic abnormalities. Optimal AAV vectors are showing success in clinical trials. Gene transfer to skeletal muscle and liver is being explored as a potential therapy for some conditions, that is, alpha1-antitrypsin (AAT) disorder and hemophilia B. Exploring approaches that enhance transduction of liver and skeletal muscle, using these vectors, is beneficial for gene therapy. Regulating hormones as an approach to improve AAV transduction is largely unexplored. In this study we tested whether insulin therapy improves liver and skeletal muscle gene transfer. In vitro studies demonstrated that the temporary coadministration (2, 8, and 24 hr) of insulin significantly improves AAV2-CMV-LacZ transduction of cultured liver cells and differentiated myofibers, but not of lung cells. In addition, there was a dose response related to this improved transduction. Interestingly, when insulin was not coadministered with the virus but given 24 hr afterward, there was no increase in the transgene product. Insulin receptor gene (INSR) expression levels were increased 5- to 13-fold in cultured liver cells and differentiated myofibers when compared with lung cells. Similar INSR gene expression profiles occurred in mouse tissues. Insulin therapy was performed in mice, using a subcutaneously implanted insulin pellet or a high-carbohydrate diet. Insulin treatment began just before intramuscular delivery of AAV1-CMV schFIX or liver-directed delivery of AAV8-CMV-schFIX and continued for 28 days. Both insulin augmentation therapies improved skeletal muscle- and liver-directed gene transduction in mice as seen by a 3.0- to 4.5-fold increase in human factor IX (hFIX) levels. The improvement was observed even after the insulin therapy ended. Monitoring insulin showed that insulin levels increased during the brief period of rAAV delivery and during the entire insulin augmentation period (28 days). This study demonstrates that AAV transduction of liver or skeletal muscle can be improved by insulin therapy. PMID- 27358026 TI - Mitochondrial health, the epigenome and healthspan. AB - Food nutrients and metabolic supply-demand dynamics constitute environmental factors that interact with our genome influencing health and disease states. These gene-environment interactions converge at the metabolic-epigenome-genome axis to regulate gene expression and phenotypic outcomes. Mounting evidence indicates that nutrients and lifestyle strongly influence genome-metabolic functional interactions determining disease via altered epigenetic regulation. The mitochondrial network is a central player of the metabolic-epigenome-genome axis, regulating the level of key metabolites [NAD(+), AcCoA (acetyl CoA), ATP] acting as substrates/cofactors for acetyl transferases, kinases (e.g. protein kinase A) and deacetylases (e.g. sirtuins, SIRTs). The chromatin, an assembly of DNA and nucleoproteins, regulates the transcriptional process, acting at the epigenomic interface between metabolism and the genome. Within this framework, we review existing evidence showing that preservation of mitochondrial network function is directly involved in decreasing the rate of damage accumulation thus slowing aging and improving healthspan. PMID- 27358032 TI - Testing the equivalence of modern human cranial covariance structure: Implications for bioarchaeological applications. AB - OBJECTIVES: Estimation of the variance-covariance (V/CV) structure of fragmentary bioarchaeological populations requires the use of proxy extant V/CV parameters. However, it is currently unclear whether extant human populations exhibit equivalent V/CV structures. MATERIALS AND METHODS: Random skewers (RS) and hierarchical analyses of common principal components (CPC) were applied to a modern human cranial dataset. Cranial V/CV similarity was assessed globally for samples of individual populations (jackknifed method) and for pairwise population sample contrasts. The results were examined in light of potential explanatory factors for covariance difference, such as geographic region, among-group distance, and sample size. RESULTS: RS analyses showed that population samples exhibited highly correlated multivariate responses to selection, and that differences in RS results were primarily a consequence of differences in sample size. The CPC method yielded mixed results, depending upon the statistical criterion used to evaluate the hierarchy. The hypothesis-testing (step-up) approach was deemed problematic due to sensitivity to low statistical power and elevated Type I errors. In contrast, the model-fitting (lowest AIC) approach suggested that V/CV matrices were proportional and/or shared a large number of CPCs. Pairwise population sample CPC results were correlated with cranial distance, suggesting that population history explains some of the variability in V/CV structure among groups. DISCUSSION: The results indicate that patterns of covariance in human craniometric samples are broadly similar but not identical. These findings have important implications for choosing extant covariance matrices to use as proxy V/CV parameters in evolutionary analyses of past populations. PMID- 27358031 TI - Unlocking the bacterial and fungal communities assemblages of sugarcane microbiome. AB - Plant microbiome and its manipulation herald a new era for plant biotechnology with the potential to benefit sustainable crop production. However, studies evaluating the diversity, structure and impact of the microbiota in economic important crops are still rare. Here we describe a comprehensive inventory of the structure and assemblage of the bacterial and fungal communities associated with sugarcane. Our analysis identified 23,811 bacterial OTUs and an unexpected 11,727 fungal OTUs inhabiting the endophytic and exophytic compartments of roots, shoots, and leaves. These communities originate primarily from native soil around plants and colonize plant organs in distinct patterns. The sample type is the primary driver of fungal community assemblage, and the organ compartment plays a major role in bacterial community assemblage. We identified core bacterial and fungal communities composed of less than 20% of the total microbial richness but accounting for over 90% of the total microbial relative abundance. The roots showed 89 core bacterial families, 19 of which accounted for 44% of the total relative abundance. Stalks are dominated by groups of yeasts that represent over 12% of total relative abundance. The core microbiome described here comprise groups whose biological role underlies important traits in plant growth and fermentative processes. PMID- 27358033 TI - Food-Grade Expression of d-Psicose 3-Epimerase with Tandem Repeat Genes in Bacillus subtilis. AB - An integrative food-grade expression system with tandem repeat target genes was constructed for the expression of d-psicose 3-epimerase (DPEase; EC 5.1.3.30). The DPEase gene fused with the P43 promoter constituted an independent monomeric expression cassette. Multimers of the expression cassette were constructed in vitro using the isocaudamer strategy. The recombinant integration plasmids pDG nDPE (n = 1, 2, 3), which contained one, two, or three consecutive P43-DPEase tandem repeats, were integrated into the genome of B. subtilis. Then, the antibiotic resistance gene was deleted by the Cre/lox system, and the food-grade recombinant B. subtilis 1A751-nDPE (n = 1, 2, 3) with integrated tandem repeats of the P43-DPEase expression cassette were generated. The specific activity of the B. subtilis 1A751-3DPE was the highest among the recombinant strains and was ~2.2-fold that of the 1A751-1DPE strain. Under the optimal conditions, 8 g/L of freeze-dried enzyme powder could convert 20% d-fructose (300 g/L) into d-allulose after 1 h. PMID- 27358034 TI - Zinc finger protein 191 inhibits hepatocellular carcinoma metastasis through discs large 1-mediated yes-associated protein inactivation. AB - Interplay between cell polarity module Scribble-Lethal Giant Larvae-Discs Large 1 (DLG1) and Yes-associated protein (YAP) appears critical in tumor metastasis. We identified zinc finger protein 191 (ZNF191) as a metastasis suppressor acting through DLG-YAP crosstalk in hepatocellular carcinoma (HCC). Overexpression of ZNF191 in HCC cells impaired cell motility, while ZNF191 depletion promoted cell migration in vitro and metastasis in vivo through triggering YAP signaling. Chromatin immunoprecipitation-sequencing revealed that ZNF191 specifically bound to the promoter of DLG1, a cell polarity maintainer and a negative regulator of YAP. The binding sequence of ZNF191 at the DLG1 promoter is a seven-repeat of TCAT motif. Double-knockdown experiments inferred that DLG1 was not only the mediator of the function of ZNF191 to suppress migration but also a link between ZNF191 and YAP signaling. Decreased expression of ZNF191 in human metastatic HCC specimens correlated positively with DLG1 levels but inversely with YAP activation. Our findings illustrate a YAP-targeting, antimetastasis function of ZNF191, thereby representing a possible prognostic marker and a potential target for metastasis therapy. CONCLUSION: ZNF191 directly binds to the DLG1 promoter at a typical TCAT repeating motif and activates the expression of DLG1; through up regulating DLG1, ZNF191 inhibits cell migration and YAP activation in HCC cells and eventually inhibits metastasis. (Hepatology 2016;64:1148-1162). PMID- 27358035 TI - Deleting myeloid IL-10 receptor signalling attenuates atherosclerosis in LDLR-/- mice by altering intestinal cholesterol fluxes. AB - Inflammatory responses and cholesterol homeostasis are interconnected in atherogenesis. Interleukin (IL)-10 is an important anti-inflammatory cytokine, known to suppress atherosclerosis development. However, the specific cell types responsible for the atheroprotective effects of IL-10 remain to be defined and knowledge on the actions of IL-10 in cholesterol homeostasis is scarce. Here we investigated the functional involvement of myeloid IL-10-mediated atheroprotection. To do so, bone marrow from IL-10 receptor 1 (IL-10R1) wild-type and myeloid IL-10R1-deficient mice was transplanted to lethally irradiated female LDLR-/- mice. Hereafter, mice were given a high cholesterol diet for 10 weeks after which atherosclerosis development and cholesterol metabolism were investigated. In vitro, myeloid IL-10R1 deficiency resulted in a pro-inflammatory macrophage phenotype. However, in vivo significantly reduced lesion size and severity was observed. This phenotype was associated with lower myeloid cell accumulation and more apoptosis in the lesions. Additionally, a profound reduction in plasma and liver cholesterol was observed upon myeloid IL-10R1 deficiency, which was reflected in plaque lipid content. This decreased hypercholesterolaemia was associated with lowered very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels, likely as a response to decreased intestinal cholesterol absorption. In addition, IL-10R1 deficient mice demonstrated substantially higher faecal sterol loss caused by increased non biliary cholesterol efflux. The induction of this process was linked to impaired ACAT2-mediated esterification of liver and plasma cholesterol. Overall, myeloid cells do not contribute to IL-10-mediated atheroprotection. In addition, this study demonstrates a novel connection between IL-10-mediated inflammation and cholesterol homeostasis in atherosclerosis. These findings make us reconsider IL 10 as a beneficial influence on atherosclerosis. PMID- 27358036 TI - Zebiriosides A-L, oleanane saponins from the roots of Dendrobangia boliviana. AB - Twelve oleanane saponins, zebiriosides A-L, were isolated from the roots of Dendrobangia boliviana Rusby, together with two known saponins, talunumoside I and 3-O-beta-d-glucuronopyranosyl serjanic acid. These saponins are glycosides of serjanic or phytolaccinic acid. Their structures were established on two basis: first, their spectral data, mainly HR-TOFESIMS, 1D-NMR ((1)H, (13)C, DEPT) and 2D NMR ((1)H(1)H COSY, TOCSY, HSQC, HMBC, and ROESY), and second by comparison with literature data. These compounds were evaluated for their cytotoxic, antileishmanial and hemolytic activities. No antileishmanial or hemolytic activities were revealed, however zebirioside C and zebirioside I showed cytotoxicity against fibroblasts with IC50 of 6.4 and 5.6 MUM, respectively. PMID- 27358037 TI - Interobserver Reliability of Three Validated Scoring Systems in the Assessment of Diabetic Foot Ulcers. AB - Scoring systems for diabetic foot ulcers may be used for clinical purposes, research or audit, to help assess disease severity, plan management, and even predict outcomes. While many have been validated in study populations, little is known about their interobserver reliability. This prospective study aimed to evaluate interobserver reliability of 3 scoring systems for diabetic foot ulceration. After sharp debridement, diabetic foot ulcers were classified by a multidisciplinary pool of trained observers, using the PEDIS (Perfusion, Extent, Depth, Infection, Sensation), SINBAD (Site, Ischemia, Neuropathy, Bacterial infection, Depth), and University of Texas (UT) wound classification systems. Interobserver reliability was assessed using intraclass correlations (0 = no agreement; 1 = complete agreement). Thirty-seven patients (78.4% male) were assessed by a pool of 12 observers. Single observer reliability was slight to moderate for all scoring systems (UT 0.53; SINBAD 0.44; PEDIS 0.23-0.42), but multiple observer reliability was almost perfect (UT 0.94; SINBAD 0.91; PEDIS 0.80-0.90). The worst agreement for single observers was when scoring infection (SINBAD 0.28; PEDIS 0.28), ischemia (SINBAD 0.26; PEDIS 0.23), or both (UT 0.25); however, this improved to almost perfect agreement for multiple observers (infection: 0.83; ischemia: 0.80-0.82; both: 0.81). These classification systems may be reliably used by multiple observers, for example, when conducting research and audit. However, they demonstrate only slight to moderate reliability when used by a single observer on an individual subject and may therefore be less helpful in the clinical setting, when documenting ulcer characteristics or communicating between colleagues. PMID- 27358038 TI - Developmental Exposure to Very Low Levels of Ethynilestradiol Affects Anxiety in a Novelty Place Preference Test of Juvenile Rats. AB - Ethinylestradiol (EE2), a synthetic mimic of 17beta-estradiol, is widespread in the environment because of its use as a contraceptive. In mammals, recent research highlighted behavioral, physiological, and morphological effects of exposition to EE2 (this xenoestrogen). We studied if developmental exposure to environmental-like, low doses of EE2 affects measures of anxiety in Sprague Dawley rats. We treated male and female rats with two doses of EE2 (4 and 400 ng/kg/day) either from GD 5 through PND 32 or from PND 1 through 21. Effects on anxiety were tested by novel place preference tests. In males and females treated from GD 5 through PND 32, a significant reduction of the time passed in the novel environment was observed. The decrease of the time spent in the novel compartment and the increase in the number of transitions between familiar and novel compartments indicate increased levels of anxiety in the EE2-treated subjects. These studies suggest that exposure to very low doses of EE2 during development can affect key behavioral traits that are modulated by anxiety. PMID- 27358040 TI - Splenic Pregnancy: A New Minimally Invasive Approach to Treatment. AB - The spleen is a rare site of abdominal ectopic pregnancy. In a review of the literature, we found 16 published cases of primary splenic pregnancies. Of the cases identified, all received surgical intervention, with one case successfully treated with laparoscopic methotrexate injection, and the rest underwent splenectomy. We would like to present a case of primary splenic pregnancy in a 35 year-old woman successfully treated with percutaneous image-guided injection of methotrexate and KCl. PMID- 27358039 TI - Inhibition of JNK-mediated autophagy enhances NSCLC cell sensitivity to mTORC1/2 inhibitors. AB - As the activation of autophagy contributes to the efficacy of many anticancer therapies, deciphering the precise role of autophagy in cancer therapy is critical. Here, we report that the dual mTORC1/2 inhibitors PP242 and OSI-027 decreased cell viability but did not induce apoptosis in the non-small cell lung cancer (NSCLC) cell lines H460 and A549. PP242 induced autophagy in NSCLC cells as demonstrated by the formation of massive vacuoles and acidic vesicular organelles and the accumulation of LC3-II. JNK was activated by PP242, and PP242 induced autophagy was blocked by inhibiting JNK pathway with SP600125 or JNK siRNA, suggesting that JNK activation is required for the mTORC1/2 inhibitor mediated induction of autophagy in NSCLC cells. Inhibiting JNK or autophagy increased the sensitivity of H460 cells to mTORC1/2 inhibitors, indicating that JNK or autophagy promoted survival in NSCLC cells treated with mTORC1/2 inhibitors. Together, these data suggest that combining mTORC1/2 inhibitors with inhibitors of JNK or autophagy might be an effective approach for improving therapeutic outcomes in NSCLC. PMID- 27358041 TI - On the Synonyms of Psathyromyia (Psathyromyia) shannoni (Dyar, 1929) and Pa. bigeniculata (Floch & Abonnenc, 1941) and the Resuscitation of Pa. pifanoi (Ortiz, 1972) With the Description of Its Female (Diptera: Psychodidae: Phlebotominae). AB - Psathyromyia shannoni until recently presented several taxa: Phlebotomus limai, Ph. bigeniculatus, Ph. pifanoi, and Ph. microcephalus as its junior synonyms. In a previous study, the two former synonyms were resurrected and here a revision based on morphological characters of the taxonomic status of Ph. microcephalus and Ph. pifanoi is presented. Psathyromyia pifanoi STAT REV; COMB N: is resurrected from the synonymy of Pa. shannoni and its female is described. Phlebotomus microcephalus is removed from the synonymy of Pa. shannoni and proposed as a new synonym of Pa. bigeniculata Lutzomyia cuzquena SYN N: , occurring in the Amazon region, is designated as a junior synonym of Pa. pifanoi The geographical distributions of Pa shannoni, Pa. bigeniculata, and Pa. pifanoi in the Americas are presented. PMID- 27358042 TI - The value of point-of-care ultrasound for detecting nail bed injury in ED. AB - OBJECTIVE: The aim of this study is to detect the value of point-of-care ultrasound (POCUS) for diagnosing a nail bed injury and fracture of distal phalanx in patients presenting with distal finger trauma to the emergency department (ED). METHODS: Patients, 18 to 65 years old, presenting with a blunt trauma of distal finger and diagnosed with subungual hematoma were eligible for the study. Subungual hematoma extending over more than 50%, fracture of distal phalanx, and disruption of periungual tissue or nail integrity were accepted as the indications for nail bed inspection. All the study patients underwent POCUS to detect the existence of a distal phalanx fracture or nail bed injury. X-ray was also obtained from all the patients. RESULTS: Nail bed was visualized in 45 patients. Squeezing and crush injury were the most reported trauma mechanism in study patients (66.7%). The sensitivity and specificity of POCUS in detecting nail bed injury were 93.4% (95% CI, 80%-99%) and 100% (95% CI, 74%-100%), respectively. The sensitivity was 100% (95% CI, 79%-100%), and specificity was 98.4% (95% CI, 91%-100%) for distal phalanx fracture. CONCLUSION: Point-of-care ultrasound is a promising tool in detecting the nail bed injury and distal phalanx fractures in patients presented with distal finger trauma. Further studies with bigger sample size are needed to reveal the diagnostic ability of POCUS before using it regularly in the ED. PMID- 27358043 TI - Are firefighters able to recognize ventricular fibrillation? Preliminary data. PMID- 27358044 TI - Fatal hemopericardium after intravenous recombinant transplasminogeen activator (rt-PA) for acute ischemic stroke. PMID- 27358045 TI - Lack of awareness among emergency physicians of potentially inappropriate medications in elderly patients at EDs. PMID- 27358046 TI - The Heptacyanotungstate(IV) Anion: A New 5 d Transition-Metal Member of the Rare Heptacyanometallate Family of Anions. AB - The heptacyanotungstate(IV) anion was isolated in the salt (n-Bu4 N)3 [W(IV) (CN)7 ] (1) from the reduction of (n-Bu4 N)3 [W(V) (CN)8 ] with concomitant loss of one cyanide ligand. The anion in 1 adopts a slightly distorted pentagonal bipyramidal geometry with an average W-C distance of 2.169 A. The spectroscopic and magnetic properties are described. PMID- 27358047 TI - Echocardiographic Evaluation of the Acute Cardiovascular Effects of an Endothelin Like Peptide Extracted from the Venom of Atractaspis irregularis. AB - Sarafotoxin-i3 from Atractaspis irregularis is a long sarafotoxin with an extended C terminus extension. Sarafotoxin-b from Atractaspis engaddensis is shorter by four amino acids. These peptides belong to the endothelin-like peptide family with a high sequence homology and similar three-dimensional structure. They act on endothelin receptors situated on the membrane of endothelial and smooth muscle cells. However, SRTX-i 3, despite a high toxicity, has a very low affinity for endothelin receptors compared to SRTX-b. The present work was carried out in order to compare the precise in vivo cardiovascular effect of SRTX b and SRTX-i3. Male Wistar rats were anesthetized and mechanically ventilated. Doppler echocardiography was performed to measure left and right ventricular functions. The rats were divided into three groups that received intravenous injections of: saline, SRTX-b or SRTX-i3. All measurements were taken at baseline, at 1 min and at 6 min after injection. Both toxins impaired cardiac output. SRTX-b impaired left ventricular function, while SRTX-i3 increased airway pressures and led to acute right ventricular dilatation associated with a decreased tricuspid annulus peak systolic velocity. SRTX-b and SRTX-i3 appear to exert toxic effects via different mechanisms, SRTX-b impairs left ventricular function, while SRTX-i3 increases airway pressures and impairs right ventricular function. PMID- 27358048 TI - Genomic alterations underlie a pan-cancer metabolic shift associated with tumour hypoxia. AB - BACKGROUND: Altered metabolism is a hallmark of cancer. However, the role of genomic changes in metabolic genes driving the tumour metabolic shift remains to be elucidated. Here, we have investigated the genomic and transcriptomic changes underlying this shift across ten different cancer types. RESULTS: A systematic pan-cancer analysis of 6538 tumour/normal samples covering ten major cancer types identified a core metabolic signature of 44 genes that exhibit high frequency somatic copy number gains/amplifications (>20 % cases) associated with increased mRNA expression (rho > 0.3, q < 10(-3)). Prognostic classifiers using these genes were confirmed in independent datasets for breast and kidney cancers. Interestingly, this signature is strongly associated with hypoxia, with nine out of ten cancer types showing increased expression and five out of ten cancer types showing increased gain/amplification of these genes in hypoxic tumours (P <= 0.01). Further validation in breast and colorectal cancer cell lines highlighted squalene epoxidase, an oxygen-requiring enzyme in cholesterol biosynthesis, as a driver of dysregulated metabolism and a key player in maintaining cell survival under hypoxia. CONCLUSIONS: This study reveals somatic genomic alterations underlying a pan-cancer metabolic shift and suggests genomic adaptation of these genes as a survival mechanism in hypoxic tumours. PMID- 27358049 TI - Reference-free deconvolution of DNA methylation data and mediation by cell composition effects. AB - BACKGROUND: Recent interest in reference-free deconvolution of DNA methylation data has led to several supervised methods, but these methods do not easily permit the interpretation of underlying cell types. RESULTS: We propose a simple method for reference-free deconvolution that provides both proportions of putative cell types defined by their underlying methylomes, the number of these constituent cell types, as well as a method for evaluating the extent to which the underlying methylomes reflect specific types of cells. We demonstrate these methods in an analysis of 23 Infinium data sets from 13 distinct data collection efforts; these empirical evaluations show that our algorithm can reasonably estimate the number of constituent types, return cell proportion estimates that demonstrate anticipated associations with underlying phenotypic data; and methylomes that reflect the underlying biology of constituent cell types. CONCLUSIONS: Our methodology permits an explicit quantitation of the mediation of phenotypic associations with DNA methylation by cell composition effects. Although more work is needed to investigate functional information related to estimated methylomes, our proposed method provides a novel and useful foundation for conducting DNA methylation studies on heterogeneous tissues lacking reference data. PMID- 27358050 TI - LATS-YAP/TAZ controls lineage specification by regulating TGFbeta signaling and Hnf4alpha expression during liver development. AB - The Hippo pathway regulates the self-renewal and differentiation of various adult stem cells, but its role in cell fate determination and differentiation during liver development remains unclear. Here we report that the Hippo pathway controls liver cell lineage specification and proliferation separately from Notch signalling, using mice and primary hepatoblasts with liver-specific knockout of Lats1 and Lats2 kinase, the direct upstream regulators of YAP and TAZ. During and after liver development, the activation of YAP/TAZ induced by loss of Lats1/2 forces hepatoblasts or hepatocytes to commit to the biliary epithelial cell (BEC) lineage. It increases BEC and fibroblast proliferation by up-regulating TGFbeta signalling, but suppresses hepatoblast to hepatocyte differentiation by repressing Hnf4alpha expression. Notably, oncogenic YAP/TAZ activation in hepatocytes induces massive p53-dependent cell senescence/death. Together, our results reveal that YAP/TAZ activity levels govern liver cell differentiation and proliferation in a context-dependent manner. PMID- 27358051 TI - Characterization of patellar maltracking using dynamic kinematic CT imaging in patients with patellar instability. AB - PURPOSE: Little has been reported on the relationship between patellar maltracking and instability. Patellar maltracking has been subjectively described with the "J sign" but is difficult to assess objectively using traditional imaging. Dynamic kinematic computed tomography (DKCT) allows dynamic assessment of the patellofemoral joint. DKCT was used to visualize and quantify patellar maltracking patterns, and severity of maltracking was correlated with the presence or absence of patellar instability symptoms. METHODS: Seventy-six knees in 38 patients were analysed using DKCT. Maltracking was defined as deviation of the patella from the trajectory of the trochlear groove and was characterized by patellar bisect offset, which was measured at 10 degrees intervals of knee flexion during active flexion and extension. Bisect offset measurements were grouped by number of quadrants of maximum lateral patellar motion, with one, two, and three quadrants corresponding to 75-99, 100-125, and >125 %, respectively. Patellar instability symptoms were correlated with maltracking severity. RESULTS: Two knees were excluded because of poor imaging quality. Fifty of 74 knees had patellar instability, and 13 patients had bilateral symptoms. Of these, four (8 %) had normal tracking patterns; 41 (82 %) had increased lateral translation in extension, which we termed the J-sign pattern; 4 (8 %) had persistent lateralization of the patella throughout range of motion; and 1 had increased lateral translation in flexion. In knees with the J-sign pattern, degree of maltracking was graded by severity: J1 (n = 24), J2 (n = 19), and J3 (n = 15). The sensitivities of J-sign grades in predicting patellar instability symptoms were 50 % (J1), 80 % (J2), and 93 % (J3) (p < 0.01). There were significant differences in sensitivity between knees with no J sign or J1 versus J2 or J3 (p = 0.02). CONCLUSION: DKCT showed several patellar maltracking patterns in patients with patellar instability. A J-sign pattern with more than two quadrants of lateral translation correlated with the presence of patellar instability symptoms. Incorporation of this approach of objectively quantifying maltracking patterns is recommended in the evaluation of patellofemoral instability. LEVEL OF EVIDENCE: IV. PMID- 27358053 TI - A model of calcium homeostasis in the rat. AB - We developed a model of calcium homeostasis in the rat to better understand the impact of dysfunctions such as primary hyperparathyroidism and vitamin D deficiency on calcium balance. The model accounts for the regulation of calcium intestinal uptake, bone resorption, and renal reabsorption by parathyroid hormone (PTH), vitamin D3, and Ca2+ itself. It is the first such model to incorporate recent findings regarding the role of the calcium-sensing receptor (CaSR) in the kidney, the presence of a rapidly exchangeable pool in bone, and the delayed response of vitamin D3 synthesis. Accounting for two (fast and slow) calcium storage compartments in bone allows the model to properly predict the effects of bisphophonates on the plasma levels of Ca2+ ([Ca2+]p), PTH, and vitamin D3 Our model also suggests that Ca2+ exchange rates between plasma and the fast pool vary with both sex and age, allowing [Ca2+]p to remain constant in spite of sex- and age-based hormonal and other differences. Our results suggest that the inconstant hypercalciuria that is observed in primary hyperparathyroidism can be attributed in part to counterbalancing effects of PTH and CaSR in the kidney. Our model also correctly predicts that calcimimetic agents such as cinacalcet bring down [Ca2+]p to within its normal range in primary hyperparathyroidism. In addition, the model provides a simulation of CYP24A1 inactivation that leads to a situation reminiscent of infantile hypercalcemia. In summary, our model of calcium handling can be used to decipher the complex regulation of calcium homeostasis. PMID- 27358054 TI - The influence of altitude hypoxia on uroflowmetry parameters in women. AB - There is scientific evidence to suggest a correlation between hypoxia and the physiology of micturition. During a Himalayan Scientific and Mountaineering Expedition, we performed tests to investigate the functional interactions between altitude hypoxia and uroflowmetry parameters in women. The tests were carried out in seven women (36.3 +/- 7.1 yr) from normoxic [1,340 meters above sea level (m a.s.l.)] to hypoxic conditions (up to 5,050 m a.s.l.) and during the return descent. The following measures were determined: uroflowmetry parameters and saturation of peripheral oxygen (SpO2 ). As expected, SpO2 decreased from 97.7 to 77.8% with increasing altitude. Micturition flow time, flow volume, and voiding time increased with altitude (P < 0.04 for all), indicating a negative correlation with SpO2 In conclusion, in young adult women, micturition physiological parameters were affected during adaptation to hypoxia; the correlation with SpO2 strongly suggests a role of hypoxia in these changes. These data could help to support the design of new strategies for both prevention and medical treatment. An example of the latter might be hyperbaric oxygen therapy, which in some studies has proved able to reduce the symptoms in patients with hypoxic bladder. PMID- 27358052 TI - High-mobility group box 1 inhibits HCO3- absorption in the medullary thick ascending limb through RAGE-Rho-ROCK-mediated inhibition of basolateral Na+/H+ exchange. AB - High-mobility group box 1 (HMGB1) is a nuclear protein released extracellularly in response to infection or injury, where it activates immune responses and contributes to the pathogenesis of kidney dysfunction in sepsis and sterile inflammatory disorders. Recently, we demonstrated that HMGB1 inhibits HCO3 (-) absorption in perfused rat medullary thick ascending limbs (MTAL) through a basolateral receptor for advanced glycation end products (RAGE)-dependent pathway that is additive to Toll-like receptor 4 (TLR4)-ERK-mediated inhibition by LPS (Good DW, George T, Watts BA III. Am J Physiol Renal Physiol 309: F720-F730, 2015). Here, we examined signaling and transport mechanisms that mediate inhibition by HMGB1. Inhibition of HCO3 (-) absorption by HMGB1 was eliminated by the Rho-associated kinase (ROCK) inhibitor Y27632 and by a specific inhibitor of Rho, the major upstream activator of ROCK. HMGB1 increased RhoA and ROCK1 activity. HMGB1-induced ROCK1 activation was eliminated by the RAGE antagonist FPS-ZM1 and by inhibition of Rho. The Rho and ROCK inhibitors had no effect on inhibition of HCO3 (-) absorption by bath LPS. Inhibition of HCO3 (-) absorption by HMGB1 was eliminated by bath amiloride, 0 Na(+) bath, and the F-actin stabilizer jasplakinolide, three conditions that selectively prevent inhibition of MTAL HCO3 (-) absorption mediated through NHE1. HMGB1 decreased basolateral Na(+)/H(+) exchange activity through activation of ROCK. We conclude that HMGB1 inhibits HCO3 (-) absorption in the MTAL through a RAGE-RhoA-ROCK1 signaling pathway coupled to inhibition of NHE1. The HMGB1-RAGE-RhoA-ROCK1 pathway thus represents a potential target to attenuate MTAL dysfunction during sepsis and other inflammatory disorders. HMGB1 and LPS inhibit HCO3 (-) absorption through different receptor signaling and transport mechanisms, which enables these pathogenic mediators to act directly and independently to impair MTAL function. PMID- 27358055 TI - The epoxyeicosatrienoic acid analog PVPA ameliorates cyclosporine-induced hypertension and renal injury in rats. AB - The introduction of calcineurin inhibitors (CNI) into clinical practice in the late 1970s transformed organ transplantation and led to significant improvement in acute rejection episodes. However, despite their significant clinical utility, the use of these agents is hampered by the development of hypertension and nephrotoxicity, which ultimately lead to end-stage kidney disease and overt cardiovascular outcomes. There are currently no effective agents to treat or prevent these complications. Importantly, CNI-free immunosuppressive regimens lack the overall efficacy of CNI-based treatments and put patients at risk of allograft rejection. Cytochrome P-450 epoxygenase metabolites of arachidonic acid, epoxyeicosatrienoic acids (EETs), have potent vasodilator and antihypertensive properties in addition to many cytoprotective effects, but their effects on CNI-induced nephrotoxicity have not been explored. Here, we show that PVPA, a novel, orally active analog of 14,15-EET, effectively prevents the development of hypertension and ameliorates kidney injury in cyclosporine-treated rats. PVPA treatment reduced proteinuria and renal dysfunction induced by cyclosporine. PVPA inhibited inflammatory cell infiltration into the kidney and decreased renal fibrosis. PVPA also reduced tubular epithelial cell apoptosis, attenuated the generation of reactive oxygen species, and modulated the unfolded protein response that is associated with endoplasmic reticulum stress. Consistent with the in vivo data, PVPA attenuated cyclosporine-induced apoptosis of NRK-52E cells in vitro. These data indicate that the cytochrome P-450/EET system offers a novel therapeutic strategy to treat or prevent CNI-induced nephrotoxicity. PMID- 27358056 TI - Altered urothelial ATP signaling in a major subset of human overactive bladder patients with pyuria. AB - Overactive Bladder (OAB) is an idiopathic condition, characterized by urgency, urinary frequency, and urgency incontinence, in the absence of routinely traceable urinary infection. We have described microscopic pyuria (>=10 wbc/MUl) in patients suffering from the worst symptoms. It is established that inflammation is associated with increased ATP release from epithelial cells, and extracellular ATP originating from the urothelium following increased hydrostatic pressure is a mediator of bladder sensation. Here, using bladder biopsy samples, we have investigated urothelial ATP signaling in OAB patients with microscopic pyuria. Basal, but not stretch-evoked, release of ATP was significantly greater from the urothelium of OAB patients with pyuria than from non-OAB patients or OAB patients without pyuria (<10 wbc/MUl). Basal ATP release from the urothelium of OAB patients with pyuria was inhibited by the P2 receptor antagonist suramin and abolished by the hemichannel blocker carbenoxolone, which differed from stretch activated ATP release. Altered P2 receptor expression was evident in the urothelium from pyuric OAB patients. Furthermore, intracellular bacteria were visualized in shed urothelial cells from ~80% of OAB patients with pyuria. These data suggest that increased ATP release from the urothelium, involving bacterial colonization, may play a role in the heightened symptoms associated with pyuric OAB patients. PMID- 27358057 TI - HMGB1/TLR4 signaling induces an inflammatory response following high-pressure renal pelvic perfusion in a porcine model. AB - Percutaneous nephrolithotomy (PCNL) causes a rapid increase in renal pelvic pressure in the kidney, which induces an inflammatory response. High-mobility group box-1 (HMGB1) is known to trigger the recruitment of inflammatory cells and the release of proinflammatory cytokines following ischemia reperfusion injury in the kidney, but the contribution of HMGB1 to the inflammatory response following high-pressure renal pelvic perfusion has not been investigated. In this study, high-pressure renal pelvic perfusion was induced in anesthetized pigs to examine the effect of HMGB1 on the inflammatory response. HMGB1 levels in the kidney increased following high-pressure renal pelvic perfusion, together with elevated levels of inflammatory cytokines in the plasma and kidney and an accumulation of neutrophils and macrophages. Inhibition of HMGB1 alleviated this inflammatory response while perfusion with recombinant HMGB1 had an augmentative effect, confirming the involvement of HMGB1 in the inflammatory response to high-pressure renal pelvic perfusion. HMGB1 regulated the inflammatory response by activating Toll-like receptor 4 (TLR4) signaling. In conclusion, this study has demonstrated that HMGB1/TLR4 signaling contributes to the inflammatory response following high pressure renal pelvic perfusion in a porcine model and has implications for the management of inflammation after PCNL. PMID- 27358058 TI - Effectiveness of Balloon Angioplasty in Children With Recurrent Aortic Coarctation Depends on the Type of Aortic Arch Pathology. AB - OBJECTIVES: The aim of this study was to evaluate the effectiveness of balloon angioplasty (BAP) for recurrent aortic coarctation (ReCoA) in infants comparing simple and complex type of aortic arch pathology (Norwood I procedure). BACKGROUND: ReCoA is a known complication after cardiovascular surgery for coarctation of the aortic arch. METHODS AND RESULTS: In a single center case study, we analyzed 20 infants undergoing BAP for ReCoA comparing simple (n = 10) and complex type of aortic arch pathology (n = 10). At catherization diameter of ReCoA stenosis was 3.2 +/- 0.7 mm (mean +/- SD) with short localized (11/20) or long hypoplastic stenosis (9/20) before and 4.8 +/- 1.2 mm after BAP (P < 0.001). Invasive systolic pressure gradient was reduced from 27.5 +/- 16.2 mmHg before to 5.1 +/- 6.6 mmHg after BAP (P < 0.001), comparable in simple and complex type of ReCoA. At day 1 after catherization noninvasive systolic arterial blood pressure gradient was reduced from 20.2 +/- 23.1 to 6.7 +/- 9.9 mmHg (P < 0.001), respectively, calculated continuous wave Doppler echo gradient from 36.3 +/- 22 to 16.8 +/- 9.6 mmHg (P < 0.01). Complications were aortic arch dissection (1/20), discrete aortic arch aneurysm formation (1/20), pericardial effusion (1/20), and peripheral arterial thrombosis (4/20). At a mid-term follow up of 9.5 months (1-40) after BAP, 3 infants needed early surgical reintervention due to secondary ReCoA, all with long hypoplastic aortic arch segments, but simple type of aortic arch pathology. CONCLUSIONS: At mid-term follow up, BAP remains an effective catheter intervention for ReCoA for infants with localized ReCoA, but not with long hypoplastic aortic arch segments, even in simple type of aortic arch pathology. PMID- 27358059 TI - Life and Death Partners in Post-PCI Restenosis: Apoptosis, Autophagy, and The Cross-talk Between Them. AB - Coronary artery disease and atherothrombosis are complex pathologic entities leading to poor clinical outcome and high cardiac mortality. Coronary artery revascularization strategies, such as percutaneous coronary intervention (PCI) in an effort to restore myocardial blood reperfusion, may only partially treat ischemic heart disease. PCI has revolutionized the revascularization for ischemiarelated cardiovascular diseases such as stable angina and acute coronary syndrome. Post-PCI restenosis, however, remains a major problem to overcome. Following the mechanical stretch, restenosis takes place in concert with the proliferation and migration of smooth muscle cells (SMCs) from the tunica media through the disruption of intima or endothelial barrier, and eventually leads to narrowed vascular lumen and obstruction. As the central pathogenetic event of restenosis, vascular neointimal hyperplasia occurs gradually as a result of the imbalance between SMC death and proliferation. Despite ample efforts, the precise mechanisms underscoring transition from initial apoptosis of vascular SMCs to apoptosis resistant proliferation remains unclear. As a conservative regulatory avenue found in nearly all mammalian cell types, autophagy plays a unique role in the delicate control on cell fate in the development of neointimal hyperplasia in post-PCI restenosis. In this mini-review, we will focus on how apoptosis, autophagy, and the cross-talk between the two govern cell death or proliferation in restenosis pathogenesis, particularly in neointimal hyperplasia involving SMCs. PMID- 27358060 TI - Pancreatic Neoplasms and Autophagy. AB - Pancreatic cancer is predicted to be the second deadliest malignancy (a median survival of 4-6 months and a 5-year survival of less than 5%) in the USA by 2020. Although current medical detection technologies have dramatically improved the survival rate for patients with other gastrointestinal malignancies, the dismal clinical outcome remains somewhat unchanged for patients with pancreatic cancer. Preclinical evidence suggests that pancreatic cancer may be benefited from early administration of systemic therapy in addition to surgery. New biomarkers should help to identify those patients possibly candidates for various systemic therapy including chemotherapy. Classical anticancer drugs such as FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin), and nabpaclitaxel plus gemcitabine only produced some modest improvements in survival. To this end, novel therapeutic avenues are sought for pancreatic cancer. This mini-review summarizes the state-of-the-art of pancreatic cancer treatment, and possible role of autophagy in therapeutics against pancreatic cancer. PMID- 27358061 TI - Liver transplantation for a patient with Turner syndrome presenting severe portal hypertension: a case report and literature review. AB - BACKGROUND: Liver involvement in Turner syndrome (TS) patients has been more clearly clarified in recent years. Most of the clinical manifestations in TS are asymptomatic and can be detected as liver test abnormalities; however, a few cases may present with end-stage liver disease and thus require liver transplantation (LT). To the best of our knowledge, only three cases undergoing LT for liver involvements in TS have been previously reported. CASE PRESENTATION: A 30-year-old female successfully underwent living donor LT for liver dysfunction related to TS syndrome. The diagnosis of TS was established by a cytogenetic analysis at 16 years of age. She received several sessions of endoscopic therapy for recurrent esophageal varices, which was complicated by ascites and spontaneous bacterial peritonitis since 27 years of age. Radiological findings of her liver before LT chronologically showed the progression of atrophy with disturbance of the major portal inflow. And then, she was finally indicated for LT. Pathologic findings of the explanted liver showed vascular abnormalities, obliterative portal venopathy, which may have induced liver dysfunction with severe portal hypertension. The patient's postoperative course was uneventful. CONCLUSIONS: The clinicopathologic information obtained by the current case can provide an insight into understanding pathophysiological mechanisms of liver involvement in TS patients. TS patients presenting with severe liver atrophy and disturbance of the major portal inflow should be indicated for LT. PMID- 27358063 TI - Thermal and near-infrared light induced spin crossover in a mononuclear iron(ii) complex with a tetrathiafulvalene-fused dipyridophenazine ligand. AB - A mononuclear Fe(ii) complex involving a tetrathiafulvalene-based ligand exhibits thermal spin-crossover (around 143 K) with pronounced hysteresis behaviour (48 K). The chromophoric and pi-extended ligand allows Near-Infrared (NIR) sensitization for the light-induced excited spin-state trapping (LIESST) with T(LIESST) = 90 K. PMID- 27358062 TI - A loss of function variant in CASP7 protects against Alzheimer's disease in homozygous APOE epsilon4 allele carriers. AB - BACKGROUND: Alzheimer's disease (AD) represents the most common form of dementia in elder populations with approximately 30 million cases worldwide. Genome wide genotyping and sequencing studies have identified many genetic variants associated with late-onset Alzheimer's disease (LOAD). While most of these variants are associated with increased risk of developing LOAD, only limited number of reports focused on variants that are protective against the disease. METHODS: Here we applied a novel approach to uncover protective alleles against AD by analyzing genetic and phenotypic data in Mount Sinai Biobank and Electronic Medical Record (EMR) databases. RESULTS: We discovered a likely loss-of-function small deletion variant in the caspase 7 (CASP7) gene associated with significantly reduced incidence of LOAD in carriers of the high-risk APOE epsilon4 allele. Further investigation of four independent cohorts of European ancestry revealed the protective effect of the CASP7 variant against AD is most significant in homozygous APOE epsilon4 allele carriers. Meta analysis of multiple datasets shows overall odds ratio = 0.45 (p = 0.004). Analysis of RNA sequencing derived gene expression data indicated the variant correlates with reduced caspase 7 expression in multiple brain tissues we examined. CONCLUSIONS: Taken together, these results are consistent with the notion that caspase 7 plays a key role in microglial activation driving neuro-degeneration during AD pathogenesis, and may explain the underlying genetic mechanisms that anti inflammatory interventions in AD show greater benefit in APOE epsilon4 carriers than non-carriers. Our findings inform potential novel therapeutic opportunities for AD and warrant further investigations. PMID- 27358064 TI - Neuropathological criteria of anti-IgLON5-related tauopathy. AB - We recently reported a novel neurological syndrome characterized by a unique NREM and REM parasomnia with sleep apnea and stridor, accompanied by bulbar dysfunction and specific association with antibodies against the neuronal cell adhesion protein IgLON5. All patients had the HLA-DRB1*1001 and HLA-DQB1*0501 alleles. Neuropathological findings in two patients revealed a novel tauopathy restricted to neurons and predominantly involving the hypothalamus and tegmentum of the brainstem. The aim of the current study is to describe the neuropathological features of the anti-IgLON5 syndrome and to provide diagnostic levels of certainty based on the presence of associated clinical and immunological data. The brains of six patients were examined and the features required for the neuropathological diagnosis were established by consensus. Additional clinical and immunological criteria were used to define "definite", "probable" and "possible" diagnostic categories. The brains of all patients showed remarkably similar features consistent with a neurodegenerative disease with neuronal loss and gliosis and absence of inflammatory infiltrates. The most relevant finding was the neuronal accumulation of hyperphosphorylated tau composed of both three-repeat (3R) and four-repeat (4R) tau isoforms, preferentially involving the hypothalamus, and more severely the tegmental nuclei of the brainstem with a cranio-caudal gradient of severity until the upper cervical cord. A "definite" diagnosis of anti-IgLON5-related tauopathy is established when these neuropathological features are present along with the detection of serum or CSF IgLON5 antibodies. When the antibody status is unknown, a "probable" diagnosis requires neuropathological findings along with a compatible clinical history or confirmation of possession of HLA-DRB1*1001 and HLA-DQB1*0501 alleles. A "possible" diagnosis should be considered in cases with compatible neuropathology but without information about a relevant clinical presentation and immunological status. These criteria should help to identify undiagnosed cases among archival tissue, and will assist future clinicopathological studies of this novel disorder. PMID- 27358066 TI - Importance of activated hepatic stellate cells and angiopoietin-1 in the pathogenesis of hepatocellular carcinoma. AB - Previous studies have determined that activated hepatic stellate cells (aHSCs) promote the progression of hepatocellular carcinoma (HCC) by increasing angiogenesis in cancerous tissues. In addition, angiopoietin 1 (Ang-1) has been reported to be involved in tumor growth and metastasis via the promotion of angiogenesis. It remains unclear whether aHSCs and Ang-1 are involved in the angiogenesis in HCC. A total of 25 HCC and tumor-adjacent tissues, and 21 normal liver tissues were used in the present study. Immunohistochemistry (IHC) was used to detect the expression of Ang-1 and alpha smooth muscle actin (alpha-SMA). The expression of CD34 was also analyzed using IHC to evaluate the microvessel density (MVD). The protein expression levels of Ang-1 were evaluated using western blot analysis. The association between aHSC, Ang-1 and angiogenesis was determined using Spearman's rank correlation coefficient. The present study determined that the expression of alpha-SMA, Ang-1 and MVD (CD34) was significantly higher in the HCC tissues when compared with tumor-adjacent tissues and normal liver tissues. Spearman's rank analysis identified a positive correlation between the expression of alpha-SMA, Ang-1 and CD34. This suggests that alpha-SMA-positive aHSCs promoted angiogenesis by expressing Ang-1, resulting in the proliferation and metastasis of HCC. PMID- 27358067 TI - The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer's disease. AB - BACKGROUND: Apolipoprotein E (APOE) E4 and low cerebrospinal fluid (CSF) amyloid beta42 (Abeta42) levels are predictors for developing Alzheimer's disease (AD). The results of several studies indicate an interaction between docosahexaenoic acid (DHA) consumption and cognitive outcomes by APOE genotype. Our objective in the present study was to examine whether APOE E4 genotype and low CSF Abeta42 levels were associated with reduced delivery of DHA to CSF in the Alzheimer's Disease Cooperative Study-sponsored DHA clinical trial. METHODS: Phospholipid DHA was assayed in the plasma of 384 participants and CSF of 70 participants at baseline. Forty-four of the 70 participants completed the 18-month follow-up visit after allocation to placebo (n = 15) or DHA (n = 29). Plasma and CSF DHA levels, CSF Abeta42, Tau, and phosphorylated Tau were measured at baseline and after the 18-month intervention. Participants were divided into tertiles based on baseline Abeta42 CSF levels. To assess DHA delivery across the blood-brain barrier, the ratio of CSF to plasma DHA levels was calculated. RESULTS: At baseline, there were no significant differences between CSF or plasma phospholipid DHA levels by CSF Abeta42 tertiles or E4 status. After 18 months of DHA supplementation, participants at the lowest Abeta42 tertile had significantly lower CSF DHA levels (p = 0.01) and lower CSF-to-plasma DHA ratios (p = 0.05) compared to the other tertiles. Baseline CSF Abeta42 levels were significantly lower in E4 carriers than in E4 noncarriers (p = 0.01). Participants carrying the E4 allele (n = 25) demonstrated a less pronounced increase in CSF DHA level compared with noncarriers (n = 4), with a possible interaction effect between treatment and APOE genotype (p = 0.07). CONCLUSIONS: APOE E4 allele and lower CSF Abeta42 levels were associated with less transport of DHA to CSF. Brain amyloid pathology may limit the delivery of DHA to the brain in AD. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00440050 . Registered on 22 Feb 2007. PMID- 27358065 TI - Epigenetic regulation in Parkinson's disease. AB - Recent efforts have shed new light on the epigenetic mechanisms driving gene expression alterations associated with Parkinson's disease (PD) pathogenesis. Changes in gene expression are a well-established cause of PD, and epigenetic mechanisms likely play a pivotal role in regulation. Studies in families with PD harboring duplications and triplications of the SNCA gene have demonstrated that gene dosage is associated with increased expression of both SNCA mRNA and protein, and correlates with a fulminant disease course. Furthermore, it is postulated that even subtle changes in SNCA expression caused by common variation is associated with disease risk. Of note, genome-wide association studies have identified over 30 loci associated with PD with most signals located in non coding regions of the genome, thus likely influencing transcript expression levels. In health, epigenetic mechanisms tightly regulate gene expression, turning genes on and off to balance homeostasis and this, in part, explains why two cells with the same DNA sequence will have different RNA expression profiles. Understanding this phenomenon will be crucial to our interpretation of the selective vulnerability observed in neurodegeneration and specifically dopaminergic neurons in the PD brain. In this review, we discuss epigenetic mechanisms, such as DNA methylation and histone modifications, involved in regulating the expression of genes relevant to PD, RNA-based mechanisms, as well as the effect of toxins and potential epigenetic-based treatments for PD. PMID- 27358068 TI - Community perceptions of pre-eclampsia in rural Karnataka State, India: a qualitative study. AB - BACKGROUND: Maternal deaths have been attributed in large part to delays in recognition of illness, timely transport to facility, and timely treatment once there. As community perceptions of pregnancy and their complications are critical to averting maternal morbidity and mortality, this study sought to contribute to the literature and explore community-based understandings of pre-eclampsia and eclampsia. METHODS: The study was conducted in rural Karnataka State, India, in 2012-2013. Fourteen focus groups were held with the following community stakeholders: three with community leaders (n = 27), two with male decision makers (n = 19), three with female decision-makers (n = 41), and six with reproductive age women (n = 132). Focus groups were facilitated by local researchers with clinical and research expertise. Discussions were audio recorded, transcribed verbatim and translated to English for thematic analysis using NVivo 10. RESULTS: Terminology exists in the local language (Kannada) to describe convulsions and hypertension, but there were no terms that are specific to pregnancy. Community participants perceived stress, tension and poor diet to be precipitants of hypertension in pregnancy. Seizures in pregnancy were thought to be brought on by anaemia, poor medical adherence, lack of tetanus toxoid immunization, and exposure in pregnancy to fire or water. Sweating, fatigue, dizziness-unsteadiness, swelling, and irritability were perceived to be signs of hypertension, which was recognized to have the potential to lead to eclampsia or death. Home remedies, such as providing the smell of onion, placing an iron object in the hands, or squeezing the fingers and toes, were all used regularly to treat seizures prior to accessing facility-based care although transport is not delayed. CONCLUSIONS: It is evident that 'pre-eclampsia' and 'eclampsia' are not well-known; instead hypertension and seizures are perceived as conditions that may occur during or outside pregnancy. Improving community knowledge about, and modifying attitudes towards, hypertension in pregnancy and its complications (including eclampsia) has the potential to address community-based delays in disease recognition and delays in treatment that contribute to maternal and perinatal morbidity and mortality. Advocacy and educational initiatives should be designed to target knowledge gaps and potentially harmful practices, and respond to cultural understandings of disease. TRIAL REGISTRATION: NCT01911494. PMID- 27358070 TI - Reliability of luminal oesophageal temperature monitoring during radiofrequency ablation of atrial fibrillation: insights from probe visualization and oesophageal reconstruction using magnetic resonance imaging. AB - Aims: A current concept to prevent atrio-oesophageal fistula during radiofrequency (RF) catheter ablation of atrial fibrillation is to monitor luminal oesophageal temperature (LET). The objective of this study was to describe the temporal course of LET and to assess the reliability of monitoring the maximal LET during pulmonary vein isolation (PVI) using irrigated multi electrode (IMEA, nMARQTM) and focal ablation catheters. Methods and results: We studied 40 patients with LET monitoring during PVI (20 patients using the IMEA and 20 patients using the focal catheter). A linear probe was used and visualized in the 3D mapping system. Left atrial and oesophageal reconstructions from delayed enhanced magnetic resonance imaging were integrated. Analysing 745 temperature profiles, LET >38 degrees C was observed in 48 of 296 (17%) and 44 of 449 (10%) ablations for the IMEA and the focal catheter, respectively (P = 0.012). Temporal latency after interruption of RF energy delivery was observed for both catheters. Time until LET baseline temperature was restored after an increase of >1 degrees C was 100 and 86 s for the IMEA and the focal catheter, respectively (P = 0.183). Imprecise representation of the maximal LET was observed in 24 (60%) and 28 patients (70%) for the left and right PVs, respectively. Conclusion: Due to the unknown exact lateral position of the LET probe within the oesophagus, the measured temperature does not necessarily reflect the maximal LET. The absence of LET increase does not rule out significant temperature increase within the oesophagus. Consequently, the temperature information of the linear multipolar probe should be used with caution. PMID- 27358069 TI - Polarity protein Crumbs homolog-3 (CRB3) regulates ectoplasmic specialization dynamics through its action on F-actin organization in Sertoli cells. AB - Crumbs homolog 3 (or Crumbs3, CRB3) is a polarity protein expressed by Sertoli and germ cells at the basal compartment in the seminiferous epithelium. CRB3 also expressed at the blood-testis barrier (BTB), co-localized with F-actin, TJ proteins occludin/ZO-1 and basal ES (ectoplasmic specialization) proteins N cadherin/beta-catenin at stages IV-VII only. The binding partners of CRB3 in the testis were the branched actin polymerization protein Arp3, and the barbed end capping and bundling protein Eps8, illustrating its possible role in actin organization. CRB3 knockdown (KD) by RNAi in Sertoli cells with an established tight junction (TJ)-permeability barrier perturbed the TJ-barrier via changes in the distribution of TJ- and basal ES-proteins at the cell-cell interface. These changes were the result of CRB3 KD-induced re-organization of actin microfilaments, in which actin microfilaments were truncated, and extensively branched, thereby destabilizing F-actin-based adhesion protein complexes at the BTB. Using Polyplus in vivo-jetPEI as a transfection medium with high efficiency for CRB3 KD in the testis, the CRB3 KD testes displayed defects in spermatid and phagosome transport, and also spermatid polarity due to a disruption of F-actin organization. In summary, CRB3 is an actin microfilament regulator, playing a pivotal role in organizing actin filament bundles at the ES. PMID- 27358071 TI - Lead-related infective endocarditis: factors influencing the formation of large vegetations. AB - Aims: The presence of intracardiac lead vegetations (ILV) is one of the important criteria for diagnosis of lead-related infective endocarditis (LRIE). The objective of the present study was to evaluate risk factors of ILV and their impact on vegetation size. Methods and results: Clinical data of 500 patients with LRIE undergoing transvenous lead extraction in 2006-15 were retrospectively analysed. The study population consisted of 352 patients with the presence of vegetations (giant, >3 cm; large, 2.0-2.9 cm; moderate-sized, 1.0-1.9 cm; and small, <1 cm) and 148 patients without ILV. We identified risk factors for vegetation occurrence and ILV size. Intracardiac lead vegetations were found more frequently in younger patients (P < 0.05), slightly more often in women (P = 0.084), and less commonly in patients with atrial fibrillation (P < 0.05). Intracardiac lead vegetation occurred significantly more frequently in patients with intracardiac lead abrasion (OR 2.373; 95% CI [1.497-3.765]; P < 0.001) and much less frequently in the concomitant presence of pocket infection (PI) (OR 0.127; 95% CI [0.074-0.218]; P < 0.00). Large vegetations were significantly more common in patients with renal failure (RF) (P < 0.001), heart failure (P < 0.001), implantable cardioverter defibrillator (P < 0.05), and loops of the leads (P < 0.001). Conclusion: Intracardiac lead abrasion is one of the most common factors influencing the occurrence of ILV. Metabolic disorders in patients with RF, heart failure, defibrillation leads, and loops of the leads were found to contribute to the formation of large vegetations. In LRIE patients, ILVs were less frequently detected in the presence of concomitant PI, indicating a different mechanism of LRIE development in patients with and without vegetations. PMID- 27358072 TI - Supersaturation of Calcipotriene and Betamethasone Dipropionate in a Novel Aerosol Foam Formulation for Topical Treatment of Psoriasis Provides Enhanced Bioavailability of the Active Ingredients. AB - INTRODUCTION: Previous studies have demonstrated the superior efficacy of a novel aerosol foam formulation of fixed combination calcipotriene 0.005% (Cal) and betamethasone dipropionate 0.064% (BD), compared with the ointment formulation. The aim of this study is to ascertain whether enhanced bioavailability of the active ingredients due to supersaturation and/or occlusive properties can explain the observed greater clinical efficacy. METHODS: Solubility and evaporation experiments were conducted to examine the abilities of Cal/BD aerosol foam ingredients to create a supersaturated environment. Optical microscopy, Raman imaging and X-ray powder diffraction were used to examine the physical state of Cal and BD in the formulations after application, and determine whether a supersaturated state remained stable for clinically relevant time periods. In vitro skin penetration and ex vivo biomarker assays were conducted to compare the skin penetration and bioavailability of Cal and BD from the aerosol foam and ointment formulations, respectively. Occlusive properties were examined via transepidermal water loss. RESULTS: Solubility studies showed that Cal and BD solubility increased with increasing dimethyl ether (DME) content. Both active ingredients are completely dissolved in the final aerosol foam formulation. DME rapidly evaporates after spraying, and the amount was reduced to 0.5% of the initial amount after 2 min. This led to the formation of a supersaturated environment, where Cal and BD crystals were absent for at least 26 h after application. Cal/BD aerosol foam had significantly greater in vitro skin penetration and had increased bioavailability compared with Cal/BD ointment. Both formulations effectively occluded the skin. CONCLUSION: A stable supersaturated solution of Cal/BD in the aerosol foam leads to increased bioavailability and explains the improved clinical effect when compared to the Cal/BD ointment. FUNDING: The studies included in the paper are all conducted by LEO Pharma A/S or CROs on behalf of LEO Pharma A/S. PMID- 27358073 TI - MiR-143-3p functions as a tumor suppressor by regulating cell proliferation, invasion and epithelial-mesenchymal transition by targeting QKI-5 in esophageal squamous cell carcinoma. AB - BACKGROUND: Dysregulation of microRNAs (miRNAs) have been demonstrated to contribute to carcinogenesis. MiR-143-3p has been identified to function as a tumor suppressor in several tumors, but the role of miR-143-3p in esophageal squamous cell carcinoma (ESCC) has not been intensively investigated. Our aim was to evaluate the potential role of miR-143-3p in the progression of ESCC. METHODS: The expression levels of miR-143-3p and QKI-5 protein were measured in 80 resected ESCC tumor specimens and the clinicopathological significance of these levels determined. We also investigated the role of miR-143-3p in the regulation of QKI-5 expression in ESCC cell lines both in vivo and in vitro. RESULTS: MiR 143-3p levels were decreased in ESCC clinical samples and low expression of miR 143-3p was significantly associated with poor prognosis in ESCC patients. Ectopic expression of miR-143-3p suppressed proliferation and induced apoptosis in ESCC cells both in vivo and in vitro. Ectopic expression of miR-143-3p also reduced the metastatic potential of cells by selectively regulating epithelial mesenchymal transition regulatory proteins. Furthermore, QKI-5 isoform was upregulated in ESCC tissues and was a direct target of miR-143-3p. Lastly, re introduction of QKI-5 expression abrogated the inhibitory effects of miR-143-3p on ESCC cell proliferation and motility. CONCLUSIONS: Our results demonstrate that miR-143-3p acts as a tumor-suppressor by targeting QKI-5 in ESCC, suggesting that miR-143-3p is a potential therapy for the treatment of ESCC. PMID- 27358077 TI - [Sepsis: case numbers increasing worldwide but new strategies too]. AB - With the numbers of cases rising worldwide and consistently high mortality, sepsis is one of the world's most significant health issues. The Jena Symposium was dedicated to the challenges in research and development, new approaches to treatment, internationally successful strategies, and a potentially successful new initiative for improving the quality of prophylaxis, early diagnosis, and therapy. The importance of intensifying efforts in the fight against sepsis is becoming increasingly recognized by health care policy. Knowledge of lay people/the public about sepsis is lacking and the standards of quality are in need of improvement. PMID- 27358074 TI - Expression and functional analysis of citrus carotene hydroxylases: unravelling the xanthophyll biosynthesis in citrus fruits. AB - BACKGROUND: Xanthophylls are oxygenated carotenoids and fulfill critical roles in plant growth and development. In plants, two different types of carotene hydroxylases, non-heme di-iron and heme-containing cytochrome P450, were reported to be involved in the biosynthesis of xanthophyll. Citrus fruits accumulate a high amount of xanthophylls, especially beta,beta-xanthophylls. To date, however, the roles of carotene hydroxylases in regulating xanthophyll content and composition have not been elucidated. RESULTS: In the present study, the roles of four carotene hydroxylase genes (CitHYb, CitCYP97A, CitCYP97B, and CitCYP97C) in the biosynthesis of xanthophyll in citrus fruits were investigated. Phylogenetic analysis showed that the four citrus carotene hydroxylases presented in four distinct clusters which have been identified in higher plants. CitHYb was a non heme di-iron carotene hydroxylase, while CitCYP97A, CitCYP97B, and CitCYP97C were heme-containing cytochrome P450-type carotene hydroxylases. Gene expression results showed that the expression of CitHYb increased in the flavedo and juice sacs during the ripening process, which was well consistent with the accumulation of beta,beta-xanthophyll in citrus fruits. The expression of CitCYP97A and CitCYP97C increased with a peak in November, which might lead to an increase of lutein in the juice sacs during the ripening process. The expression level of CitCYP97B was much lower than that of CitHYb, CitCYP97A, and CitCYP97C in the juice sacs during the ripening process. Functional analysis showed that the CitHYb was able to catalyze the hydroxylation of the beta-rings of beta-carotene and alpha-carotene in Escherichia coli BL21 (DE3) cells. Meanwhile, when CitHYb was co-expressed with CitCYP97C, alpha-carotene was hydroxylated on the beta-ring and epsilon-ring sequentially to produce lutein. CONCLUSIONS: CitHYb was a key gene for beta,beta-xanthophyll biosynthesis in citrus fruits. CitCYP97C functioned as an epsilon-ring hydroxylase to produce lutein using zeinoxanthin as a substrate. The results will contribute to elucidating xanthophyll biosynthesis in citrus fruits, and provide new strategies to improve the nutritional and commercial qualities of citrus fruits. PMID- 27358076 TI - [Mortui vivos docent : The dead teach the living]. AB - There are considerable similarities and intersections between forensic medicine and emergency medicine. This applies especially to frustraneously resuscitated patients or other lethal clinical courses of traumatized patients who are subject to latter forensic autopsy. Cooperation between departments of emergency and forensic medicine not only has emergency medical training potential, but also the possibility of retrospective evaluation of medical emergency measures - both in individual cases and with regard to epidemiological aspects. In particular, the widespread registration of autopsied pre-hospital trauma deaths that occurred despite on-scene resuscitation attempts is useful. The pre-hospital situation represents a hotspot, but also a blind spot in the overall trauma mortality. In recent clinical registers, preclinical deaths go mostly unrecorded, despite the undisputed benefits of clinical registers. PMID- 27358079 TI - Erratum to: Evidence-based clinical practice guidelines for polycystic kidney disease 2014. PMID- 27358078 TI - A national evaluation of a dissemination and implementation initiative to enhance primary care practice capacity and improve cardiovascular disease care: the ESCALATES study protocol. AB - BACKGROUND: The Agency for Healthcare Research and Quality (AHRQ) launched the EvidenceNOW Initiative to rapidly disseminate and implement evidence-based cardiovascular disease (CVD) preventive care in smaller primary care practices. AHRQ funded eight grantees (seven regional Cooperatives and one independent national evaluation) to participate in EvidenceNOW. The national evaluation examines quality improvement efforts and outcomes for more than 1500 small primary care practices (restricted to those with fewer than ten physicians per clinic). Examples of external support include practice facilitation, expert consultation, performance feedback, and educational materials and activities. This paper describes the study protocol for the EvidenceNOW national evaluation, which is called Evaluating System Change to Advance Learning and Take Evidence to Scale (ESCALATES). METHODS: This prospective observational study will examine the portfolio of EvidenceNOW Cooperatives using both qualitative and quantitative data. Qualitative data include: online implementation diaries, observation and interviews at Cooperatives and practices, and systematic assessment of context from the perspective of Cooperative team members. Quantitative data include: practice-level performance on clinical quality measures (aspirin prescribing, blood pressure and cholesterol control, and smoking cessation; ABCS) collected by Cooperatives from electronic health records (EHRs); practice and practice member surveys to assess practice capacity and other organizational and structural characteristics; and systematic tracking of intervention delivery. Quantitative, qualitative, and mixed methods analyses will be conducted to examine how Cooperatives organize to provide external support to practices, to compare effectiveness of the dissemination and implementation approaches they implement, and to examine how regional variations and other organization and contextual factors influence implementation and effectiveness. DISCUSSION: ESCALATES is a national evaluation of an ambitious large-scale dissemination and implementation effort focused on transforming smaller primary care practices. Insights will help to inform the design of national health care practice extension systems aimed at supporting practice transformation efforts in the USA. CLINICAL TRIAL REGISTRATION: NCT02560428 (09/21/15). PMID- 27358080 TI - Computer-aided cephalometric landmark annotation for CBCT data. AB - PURPOSE: Nowadays, with the increased diffusion of Cone Beam Computerized Tomography (CBCT) scanners in dental and maxillo-facial practice, 3D cephalometric analysis is emerging. Maxillofacial surgeons and dentists make wide use of cephalometric analysis in diagnosis, surgery and treatment planning. Accuracy and repeatability of the manual approach, the most common approach in clinical practice, are limited by intra- and inter-subject variability in landmark identification. So, we propose a computer-aided landmark annotation approach that estimates the three-dimensional (3D) positions of 21 selected landmarks. METHODS: The procedure involves an adaptive cluster-based segmentation of bone tissues followed by an intensity-based registration of an annotated reference volume onto a patient Cone Beam CT (CBCT) head volume. The outcomes of the annotation process are presented to the clinician as a 3D surface of the patient skull with the estimate landmark displayed on it. Moreover, each landmark is centered into a spherical confidence region that can help the clinician in a subsequent manual refinement of the annotation. The algorithm was validated onto 18 CBCT images. RESULTS: Automatic segmentation shows a high accuracy level with no significant difference between automatically and manually determined threshold values. The overall median value of the localization error was equal to 1.99 mm with an interquartile range (IQR) of 1.22-2.89 mm. CONCLUSION: The obtained results are promising, segmentation was proved to be very robust and the achieved accuracy level in landmark annotation was acceptable for most of landmarks and comparable with other available methods. PMID- 27358082 TI - Brexit threatens stability of medical science workforce, researchers have warned. PMID- 27358081 TI - Custom implant design for large cranial defects. AB - PURPOSE: The aim of this work was to introduce a computer-aided design (CAD) tool that enables the design of large skull defect (>100 [Formula: see text]) implants. Functional and aesthetically correct custom implants are extremely important for patients with large cranial defects. For these cases, preoperative fabrication of implants is recommended to avoid problems of donor site morbidity, sufficiency of donor material and quality. Finally, crafting the correct shape is a non-trivial task increasingly complicated by defect size. METHODS: We present a CAD tool to design such implants for the neurocranium. A combination of geometric morphometrics and radial basis functions, namely thin-plate splines, allows semiautomatic implant generation. The method uses symmetry and the best fitting shape to estimate missing data directly within the radiologic volume data. In addition, this approach delivers correct implant fitting via a boundary fitting approach. RESULTS: This method generates a smooth implant surface, free of sharp edges that follows the main contours of the boundary, enabling accurate implant placement in the defect site intraoperatively. The present approach is evaluated and compared to existing methods. A mean error of 89.29 % (72.64-100 %) missing landmarks with an error less or equal to 1 mm was obtained. CONCLUSION: In conclusion, the results show that our CAD tool can generate patient-specific implants with high accuracy. PMID- 27358083 TI - Semiclassical Transition-State Theory Based on Fourth-Order Vibrational Perturbation Theory: The Symmetrical Eckart Barrier. AB - Semiclassical transition-state theory based on fourth-order vibrational perturbation theory (VPT4-SCTST) is applied to compute the barrier transmission coefficient for the symmetric Eckart potential. For a barrier parametrized to mimic the H2 + H exchange reaction, the results obtained are in excellent agreement with exact quantum calculations over a range of energy that extends down to roughly 1% of the barrier height, V0, where tunneling is negligible. The VPT2-SCTST treatment, which is commonly used in chemical kinetics studies, also performs quite well but already shows an error of a few percent at ca. 0.8 V0 where tunneling is still important. This suggests that VPT4-SCTST could offer an improvement over VPT2-SCTST in applications studies. However, the computational effort for VPT4-SCTST treatments of molecules is excessive, and any improvement gained is unlikely to warrant the increased effort. Nevertheless, the treatment of the symmetric Eckart barrier problem here suggests a simple modification of the usual VPT2-SCTST protocol that warrants further investigation. PMID- 27358084 TI - Usefulness of T2 star-weighted imaging in ovarian cysts and tumors. AB - AIM: The aim of this study was to investigate the prevalence of hypointensity on T2 star-weighted imaging (T2*WI), which is useful for detecting hemosiderin, in endometriomas and other ovarian tumors. The efficacy of detecting adhesions around ovarian tumors was also investigated. METHODS: Pelvic magnetic resonance (MR) examinations, including T2*WI, were carried out. The inclusion criteria were female patients with ovarian surgical treatments. One hundred seventeen patients with a total of 147 lesions were enrolled. Two radiologists retrospectively evaluated MR imaging (MRI) to predict ovarian pathology and the presence of adhesions. T2*WI hypointensity of the inside and outside along ovarian cysts/tumors was utilized to predict pathological diagnoses and the presence of adhesions, respectively. The kappa scores were calculated to measure interobserver agreement on MRI findings. The MRI interpretations were compared with the results of pathological investigation and surgical observations. RESULTS: Hypointensity inside along the cyst walls on T2*WI was observed in 100 out of 106 lesions of endometriomas (94.3%), and three out of 41 non-endometrial ovarian cysts/tumors (7.3%). Four different patterns of T2*WI were observed in ovarian cysts/tumors. The kappa score regarding T2*WI hypointensity inside along the cyst walls was 0.633. Using conventional routine pelvic MRI, the sensitivity for detecting adhesions around ovarian cysts was 84.5%. By adding T2*WI, the sensitivity improved to 91.4% (P < 0.01). With conventional methods to predict adhesions, the kappa score was 0.660. After adding T2*WI to the conventional methods, the kappa score was 0.767. CONCLUSION: Hypointensity on T2*WI was observed frequently in endometrioma. T2*WI also improved the sensitivity for detecting adhesions around ovarian cysts/tumors. PMID- 27358085 TI - Array of nanosheets render ultrafast and high-capacity Na-ion storage by tunable pseudocapacitance. AB - Sodium-ion batteries are a potentially low-cost and safe alternative to the prevailing lithium-ion battery technology. However, it is a great challenge to achieve fast charging and high power density for most sodium-ion electrodes because of the sluggish sodiation kinetics. Here we demonstrate a high-capacity and high-rate sodium-ion anode based on ultrathin layered tin(II) sulfide nanostructures, in which a maximized extrinsic pseudocapacitance contribution is identified and verified by kinetics analysis. The graphene foam supported tin(II) sulfide nanoarray anode delivers a high reversible capacity of ~1,100 mAh g(-1) at 30 mA g(-1) and ~420 mAh g(-1) at 30 A g(-1), which even outperforms its lithium-ion storage performance. The surface-dominated redox reaction rendered by our tailored ultrathin tin(II) sulfide nanostructures may also work in other layered materials for high-performance sodium-ion storage. PMID- 27358086 TI - Intravenous immunoglobulin in paediatric neurology: evaluating effective usage and outcomes. PMID- 27358087 TI - Tin-based composite anodes for potassium-ion batteries. AB - The electrochemical behaviour of a Sn-based anode in a potassium cell is reported for the first time. The material is active at low potentials vs. K/K(+), and encouraging capacities of around 150 mA h g(-1) are recorded. Experimental evidence shows that Sn is capable of alloying/de-alloying with potassium in a reversible manner. PMID- 27358088 TI - Vascular Health Assessment of The Hypertensive Patients (VASOTENS) Registry: Study Protocol of an International, Web-Based Telemonitoring Registry for Ambulatory Blood Pressure and Arterial Stiffness. AB - BACKGROUND: Hypertension guidelines recommend ambulatory blood pressure (ABP), central aortic pressure (CAP), and pulse wave velocity (PWV) as parameters for estimating blood pressure (BP) control and vascular impairment. Recent advances in technology have enabled devices to combine non-invasive estimation of these parameters over the 24-hour ABP monitoring. However, currently there is limited evidence on the usefulness of such an approach for routine hypertension management. OBJECTIVE: We recently launched an investigator-initiated, international, multicenter, observational, prospective study, the Vascular health Assessment Of The Hypertensive patients (VASOTENS) Registry, aimed at (1) evaluating non-invasive 24-hour ABP and arterial stiffness estimates (through 24 hour pulse wave analysis, PWA) in hypertensive subjects undergoing ambulatory blood pressure monitoring (ABPM) for clinical reasons; (2) assessing the changes in estimates following treatment; (3) weighing the impact of 24-hour PWA on target organ damage and cardiovascular prognosis; (4) assessing the relationship between arterial stiffness, BP absolute mean level and variability, and prognosis; and (5) validating the use of a 24-hour PWA electronic health (e health) solution for hypertension screening. METHODS: Approximately 2000 subjects, referred to 20 hypertension clinics for routine diagnostic evaluation and follow-up of hypertension of any severity or stage, will be recruited. Data collection will include ABPM, performed with a device allowing simultaneous non invasive assessment of 24-hour CAP and arterial stiffness (BPLab), and clinical data (including cardiovascular outcomes). As recommended by current guidelines, each patient will be followed-up with visits occurring at regular intervals (ideally every 6 months, and not less than once a year depending on disease severity). A Web-based telemedicine platform (THOLOMEUS) will be used for data collection. The use of the telemedicine system will allow standardized and centralized data collection, data validation by experts and counseling to remote centers, setup and maintenance of the Registry, and prompt data analysis. RESULTS: First follow-up results are expected to be available in the next 2 years. CONCLUSIONS: The results of the VASOTENS Registry will help define the normalcy thresholds for current and future indices derived from 24-hour PWA, according to outcome data, and will also provide supporting evidence for the inclusion of this type of evaluation in hypertension management. TRIAL REGISTRATION: Clinicaltrials.gov NCT02577835; https://clinicaltrials.gov/ct2/show/NCT02577835 (Archived by WebCite at http://www.Webcitation.org/6hzZBKY2Q). PMID- 27358089 TI - Effect of feed supplementation with live yeast on the intestinal transcriptome profile of weaning pigs orally challenged with Escherichia coli F4. AB - The ability of live yeasts to modulate pig intestinal cell signals in response to infection with Escherichia coli F4ac (ETEC) has not been studied in-depth. The aim of this trial was to evaluate the effect of Saccharomyces cerevisiae CNCM I 4407 (Sc), supplied at different times, on the transcriptome profile of the jejunal mucosa of pigs 24 h after infection with ETEC. In total, 20 piglets selected to be ETEC-susceptible were weaned at 24 days of age (day 0) and allotted by litter to one of following groups: control (CO), CO+colistin (AB), CO+5*1010 colony-forming unit (CFU) Sc/kg feed, from day 0 (PR) and CO+5*1010 CFU Sc/kg feed from day 7 (CM). On day 7, the pigs were orally challenged with ETEC and were slaughtered 24 h later after blood sampling for haptoglobin (Hp) and C reactive protein (CRP) determination. The jejunal mucosa was sampled (1) for morphometry; (2) for quantification of proliferation, apoptosis and zonula occludens (ZO-1); (3) to carry out the microarray analysis. A functional analysis was carried out using Gene Set Enrichment Analysis. The normalized enrichment score (NES) was calculated for each gene set, and statistical significance was defined when the False Discovery Rate % was <25 and P-values of NES were <0.05. The blood concentration of CRP and Hp, and the score for ZO-1 integrity on the jejunal villi did not differ between groups. The intestinal crypts were deeper in the AB (P=0.05) and the yeast groups (P<0.05) than in the CO group. Antibiotic treatment increased the number of mitotic cells in intestinal villi as compared with the control group (P<0.05). The PR group tended to increase the mitotic cells in villi and crypts and tended to reduce the cells in apoptosis as compared with the CM group. The transcriptome profiles of the AB and PR groups were similar. In both groups, the gene sets involved in mitosis and in mitochondria development ranked the highest, whereas in the CO group, the gene sets related to cell junction and anion channels were affected. In the CM group, the gene sets linked to the metabolic process, and transcription ranked the highest; a gene set linked with a negative effect on growth was also affected. In conclusion, the constant supplementation in the feed with the strain of yeast tested was effective in counteracting the detrimental effect of ETEC infection in susceptible pigs limits the early activation of the gene sets related to the impairment of the jejunal mucosa. PMID- 27358090 TI - Workforce Interventions to Deliver Postnatal Care to Improve Neonatal Outcomes in Low- and Lower-Middle-Income Countries: A Narrative Synthesis. AB - Reducing neonatal mortality rates in low- and lower-middle-income countries (LMICs) requires postnatal interventions to be delivered through an appropriately prepared and supported workforce. This review examines health workforce interventions that deliver integrated packages of postnatal care to improve neonatal outcomes in LMICs. We conducted a structured search of peer-reviewed articles published during 2003-2014 that investigated the delivery of postnatal interventions by formal and lay health workers. We selected 13 studies and analyzed them using a narrative synthesis methodology. This review observed a wide divergence among studies regarding the outcomes as well as the approaches and duration of workforce training and staff supervision. Except 4, all studies observed a significant reduction in neonatal mortality. On the other hand, teams of lay health workers appear to be more effective in improving neonatal outcomes. Further improvement in the performance of health care providers may require emphasis on workforce interventions such as competency assessment, the acquisition of appropriate skills, and supervisory guidelines. Nevertheless, the heterogeneity and limited number of studies do not allow us to arrive at definitive conclusions, and we recommend the need for the harmonization of future studies, with uniformity of outcome measures and cost analyses. PMID- 27358092 TI - Coexistent digital gouty and infective flexor tenosynovitis. AB - Flexor tenosynovitis of the hand is often caused by trauma or infection. Gouty tenosynovitis is an uncommon presentation of the condition and is usually misdiagnosed as infection with the patient undergoing surgery. The coexistence of infection and gout causing flexor tenosynovitis has never been described before in the literature; we report the first ever case and emphasise the importance of its awareness for optimal treatment. A 54-year-old man was initially diagnosed and treated as having infective flexor tenosynovitis and, later, due to a lack of improvement in his symptoms, was discovered to also have gout. We review the literature and suggest management strategy for use in daily clinical practice, including an algorithm, for this presentation. PMID- 27358091 TI - Cocooned by complications: fetal survival through placental adherence. AB - We report a case of a 31-year-old woman with 2 previous caesarean deliveries who presented a diagnostic dilemma. She underwent caesarean section where she was found to have a uterine scar dehiscence with an adherent placenta and required a hysterectomy. While individually representing high risk to the mother and/or fetus, the combination in this case protected the fetus. PMID- 27358093 TI - Necrotic lesions of the caecum: a rare cause of right iliac fossa pain. PMID- 27358094 TI - Painful knees and hearing-loss: a rare presentation of meningococcal disease. AB - A 49-year-old woman with a medical history of rheumatoid arthritis presented to the emergency room, with high fever and painful knees. In addition, she had had a mild headache for several days and some hearing loss over several months. We saw an ill patient with arthritis of both knees, from which purulent fluid was aspirated. Antibiotics were started for septic arthritis of both knees and her condition improved rapidly. However, the headache persisted and the hearing loss worsened. At the time, meningitis was suspected. Initial knee aspiration culture was positive for Neisseria meningitidis PCR of the cerebrospinal fluid sample also was positive for N. meningitidis The patient was finally diagnosed with bilateral septic gonarthritis secondary to a bacterial meningitis caused by N. meningitidis. PMID- 27358095 TI - Assessment of PTEN-associated vascular malformations in a patient with Bannayan Riley-Ruvalcaba syndrome. AB - Misdiagnosis of phosphatase and tensin homologue hamartoma syndromes is common. Correct diagnosis has a relevant impact on patients, as the risk of malignancies is high and treatment options are limited. We report the case of a 24-year-old man who presented with symptomatic vascular intramuscular lesions of the left forearm and right calf, macrocephaly, post Hashimoto thyroiditis, a multicystic intracranial paratrigonal lesion, lentiginous hyperpigmented maculae on the foreskin and multiple skin lesions. MRI showed extended fibrofatty changes and malformed vessels in the forearm and calf lesions, also, arteriovenous shunting was present in these lesions. The patient had been treated by embolisation and surgically in the past, with limited results. A multidisciplinary assessment and genetic counselling were undertaken and a surveillance programme was initiated. Treatment options of the symptomatic vascular lesions include excision or possibly cryoablation. Physiotherapy to prevent progression of the contractures should be initiated meanwhile. PMID- 27358096 TI - Thermal dysregulation in Prader-Willi syndrome: a potentially fatal complication in adolescence, not just in infancy. AB - A 13-year-old boy with a background of Prader-Willi syndrome (PWS) was admitted to the regional paediatric intensive care unit, with community-acquired pneumonia. Despite a week of intravenous antibiotics, resolution of inflammatory markers and resolving consolidation on radiograph, he remained feverish. Fever of unknown origin investigations were negative and he was diagnosed with central thermal dysregulation secondary to hypothalamic dysfunction in PWS. Following a hyperpyrexia period, secondary rhabdomyolysis and renal failure developed. This was successfully managed with active cooling, ventilation and haemofiltration. After weaning from haemofiltration, the patient was successfully extubated to non invasive respiratory support. PMID- 27358097 TI - Incidental diagnosis of an H-type tracheo-oesophageal fistula. AB - A 6-day-old term neonate who was intubated on day 1 of life for apnoeic episodes, was transferred to the regional paediatric intensive care unit (PICU) for specialist opinion following 3 failed extubations in the neonatal unit. Escherichia coli congenital pneumonia was diagnosed and the child discharged to the local hospital. Chest radiographs and inflammatory markers were in keeping with infection. However, ongoing difficulties with secretions necessitated readmission to the PICU, following a significant cyanotic episode associated with coughing. On arrival at the PICU, a large leak around the endotracheal tube (ETT) was noted. On direct laryngoscopy, the ETT was found correctly positioned, through the cords, but air was noted to be coming back from the oesophagus. Advancing the ETT towards the carina terminated the leak and raised the suspicion of a tracheo-oesophageal fistula. An H-type tracheo-oesophageal fistula was confirmed on bronchoscopy. An uneventful fistula repair was performed and the baby discharged from the PICU on day 23 of life. PMID- 27358098 TI - Difficult diagnosis: strangulated obturator hernia in an 88-year-old woman. AB - The obturator hernia is a rare type of hernia that can present a diagnostic challenge for the clinician. We report a case of an 88-year-old woman who presented with a history of right iliac fossa pain, bilious vomiting and diarrhoea. Non-specific findings on examination and blood tests made the diagnosis difficult, however, a CT scan of her abdomen revealed the site of the obstruction and the patient was taken to theatre for emergency surgery. We review the literature with focus on the diagnosis of obturator hernias and the different surgical approaches used. The authors believe that this case is of educational value to healthcare professionals, particularly those working in general practice, emergency departments and on surgical teams. It highlights to doctors that patients with incarcerated obturator hernias can present with or without overt signs of intestinal obstruction and emphasises the fact that an obturator hernia can be an important cause of intestinal obstruction in a thin, elderly woman. PMID- 27358099 TI - Acute ST elevation myocardial infarction in fulminant systemic p-ANCA vasculitis: a rare catastrophic complication. AB - A 45-year-old Caucasian man presented to the hospital with a 3-month history of fatigue, bilateral upper and lower limb paresthesias and gradually worsening ascending paralysis. A few weeks later, he developed acute renal failure requiring haemodialysis. Investigations revealed presence of myeloperoxidase (MPO) perinuclear antineutrophil cytoplasmic antibodies (ANCA). Renal biopsy was conclusive for rapidly progressive glomerulonephritis with crescents. Treatment for ANCA positive vasculitis was initiated with pulsed steroids, cyclophosphamide and plasmapheresis. The hospital course took an unexpected turn when the patient developed acute chest pain with an EKG consistent with inferior ST elevation myocardial infarction (STEMI). Urgent left heart catheterisation revealed distal occlusions in multivessel coronary distribution. Coronary involvement is rare in ANCA vasculitis and STEMI has not been reported in MPO-ANCA positive vasculitis, to the best of our knowledge. PMID- 27358100 TI - Spontaneous pneumoperitoneum with subcutaneous emphysema. PMID- 27358101 TI - Elderly man with a pulmonary mass and osteolytic lesions: is it primary pulmonary plasmacytoma or multiple myeloma with an extramedullary pulmonary nodule? PMID- 27358102 TI - Maxillofacial fibrous dysplasia: a diagnostic challenge. AB - A 30-year-old woman presented for orthodontic treatment, with a chief symptom of a 'shifting bite' and concurrent facial asymmetry with aesthetic concerns. The patient had previously received treatment from several general dentists and several specialists, without accurate diagnosis. Radiological investigation coupled with biopsy confirmed a diagnosis of fibrous dysplasia. Proper diagnosis led to changes in the treatment plan and gave the patient realistic expectations about the options she had for the outcome of treatment. Prompt diagnosis by dental practitioners is critical to patient satisfaction and successful outcome; therefore, it is important to familiarise ourselves with the signs, symptoms and proper course of management of fibrous dysplasia. PMID- 27358104 TI - Probit vs. semi-nonparametric estimation: examining the role of disability on institutional entry for older adults. AB - PURPOSE: The purpose of this study was to showcase an advanced methodological approach to model disability and institutional entry. Both of these are important areas to investigate given the on-going aging of the United States population. By 2020, approximately 15% of the population will be 65 years and older. Many of these older adults will experience disability and require formal care. METHODS: A probit analysis was employed to determine which disabilities were associated with admission into an institution (i.e. long-term care). Since this framework imposes strong distributional assumptions, misspecification leads to inconsistent estimators. To overcome such a short-coming, this analysis extended the probit framework by employing an advanced semi-nonparamertic maximum likelihood estimation utilizing Hermite polynomial expansions. RESULTS: Specification tests show semi-nonparametric estimation is preferred over probit. In terms of the estimates, semi-nonparametric ratios equal 42 for cognitive difficulty, 64 for independent living, and 111 for self-care disability while probit yields much smaller estimates of 19, 30, and 44, respectively. CONCLUSIONS: Public health professionals can use these results to better understand why certain interventions have not shown promise. Equally important, healthcare workers can use this research to evaluate which type of treatment plans may delay institutionalization and improve the quality of life for older adults. Implications for rehabilitation With on-going global aging, understanding the association between disability and institutional entry is important in devising successful rehabilitation interventions. Semi-nonparametric is preferred to probit and shows ambulatory and cognitive impairments present high risk for institutional entry (long-term care). Informal caregiving and home-based care require further examination as forms of rehabilitation/therapy for certain types of disabilities. PMID- 27358103 TI - Multiple brown tumours from parathyroid carcinoma. AB - We report a case of a 29-year-old woman who suffered from severe bilateral inguinal pain and left mandibular mass. CT scan showed innumerable expansile osteolytic bone masses on the iliac wings, femur, ribs and vertebral bodies, diffuse skeletal osteopaenia, calyceal lithiasis on the right kidney and a left thyroid mass. Ionised calcium and intact parathyroid hormone (PTH) were elevated. Parathyroid sestamibi scan showed a hyperfunctioning left inferior parathyroid gland. Biopsy of the left mandibular mass was consistent with brown tumour. The patient underwent parathyroidectomy of the enlarged parathyroid gland. Final histopathology, however, revealed parathyroid carcinoma, 4.7 cm in widest dimension, with capsular and vascular space invasion. The patient underwent repeat surgery, specifically, left thyroid lobectomy, isthmectomy and central node dissection. Intact PTH decreased from 681.3 to 74 pg/mL (normal range: 10 65) 24 hours postoperatively. Follow-up at 6 months showed normal serum calcium levels, size reduction of bone lesions and improvement of quality of life. PMID- 27358105 TI - Papular mucinosis with monotypic plasma cells in a child. PMID- 27358106 TI - Solid lipid nanoparticles carrying lipophilic derivatives of doxorubicin: preparation, characterization, and in vitro cytotoxicity studies. AB - Doxorubicin (DOXO) lauroyl ester and amide were proposed as lipophilic derivatives and entrapped in SLNs. DOXO derivatives-loaded SLNs were spherical shaped, had 200-300 nm mean diameters and showed 80-94% w/w drug entrapment efficiencies. The effect of DOXO derivatives-loaded SLNs and free DOXO on cell growth was examined by MTT and colony-forming assays on four different tumour cell lines: a pancreatic, CFPAC-1, a lung, A549, and two ovarian, A2780 and A2780res (DOXO-resistant). The results obtained with MTT and colony-forming assay show that although DOXO displayed an inhibition of cell proliferation greater or similar to DOXO lauroyl amide-loaded SLNs on all cell types, the effect induced by DOXO lauroyl ester-loaded SLNs was higher and concentration-dependent, and it was the only one maintained at 10(-5 )mM concentration. Only DOXO lauroyl ester loaded SLNs were able to induce a 40% inhibitory effect on A2780 res cell line up to 10(-4 )mM concentration. PMID- 27358107 TI - Guillain-Barre syndrome following acute co-super-infection of hepatitis E virus and cytomegalovirus in a chronic hepatitis B virus carrier. AB - Guillain-Barre syndrome (GBS) is a rare neurological complication of hepatitis B. GBS presence in acute hepatitis E virus (HEV) and cytomegalovirus (CMV) infection is also sporadically reported. Here, a rare case of GBS in a chronic Hepatitis B virus carrier co-infected with HEV and CMV was reported. Based on the analysis on the progress of the manifestations and virus serological detection results, it could be concluded that GBS might mostly likely result from super-infection of HEV and CMV. This case report is clinically important in that it provides a good example of differential diagnosis and appropriate treatment on such a rare but life-threatening case. J. Med. Virol. 89:368-372, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27358108 TI - A Structure-free Method for Quantifying Conformational Flexibility in proteins. AB - All proteins sample a range of conformations at physiologic temperatures and this inherent flexibility enables them to carry out their prescribed functions. A comprehensive understanding of protein function therefore entails a characterization of protein flexibility. Here we describe a novel approach for quantifying a protein's flexibility in solution using small-angle X-ray scattering (SAXS) data. The method calculates an effective entropy that quantifies the diversity of radii of gyration that a protein can adopt in solution and does not require the explicit generation of structural ensembles to garner insights into protein flexibility. Application of this structure-free approach to over 200 experimental datasets demonstrates that the methodology can quantify a protein's disorder as well as the effects of ligand binding on protein flexibility. Such quantitative descriptions of protein flexibility form the basis of a rigorous taxonomy for the description and classification of protein structure. PMID- 27358109 TI - Whose voices? Patient and public involvement in clinical commissioning. AB - AIM: This paper aims to explore patient and public representation in a NHS clinical commissioning group and how this is experienced by staff and lay members involved. BACKGROUND: Patient and public involvement is believed to foster greater public representativeness in the development and delivery of health care services. However, there is widespread debate about what representation is or what it should be. Questions arise about the different constructions of representation and the representativeness of patients and the public in decision making structures and processes. DESIGN: Ethnographic, two-phase study involving twenty-four observations across two types of clinical commissioning group meetings with patient and public involvement, fourteen follow-up interviews with NHS staff and lay members, and a focus group with five lay members. RESULTS: Perceptions of what constitutes legitimate representativeness varied between respondents, ranging from representing an individual patient experience to reaching large numbers of people. Consistent with previous studies, there was a lack of clarity about the role of lay members in the work of the clinical commissioning group. CONCLUSIONS: Unlike previous studies, it was lay members, not staff, who raised concerns about their representativeness and legitimacy. Although the clinical commissioning group provides resources to support patient and public involvement, there continues to be a lack of clarity about roles and scope for impact. Lay members are still some way from constituting a powerful voice at the table. PMID- 27358110 TI - HDAC6 Deacetylates HMGN2 to Regulate Stat5a Activity and Breast Cancer Growth. AB - : Stat5a is a transcription factor utilized by several cytokine/hormone receptor signaling pathways that promotes transcription of genes associated with proliferation, differentiation, and survival of cancer cells. However, there are currently no clinically approved therapies that directly target Stat5a, despite ample evidence that it contributes to breast cancer pathogenesis. Here, deacetylation of the Stat5a coactivator and chromatin-remodeling protein HMGN2 on lysine residue K2 by HDAC6 promotes Stat5a-mediated transcription and breast cancer growth. HDAC6 inhibition both in vitro and in vivo enhances HMGN2 acetylation with a concomitant reduction in Stat5a-mediated signaling, resulting in an inhibition of breast cancer growth. Furthermore, HMGN2 is highly acetylated at K2 in normal human breast tissue, but is deacetylated in primary breast tumors and lymph node metastases, suggesting that targeting HMGN2 deacetylation is a viable treatment for breast cancer. Together, these results reveal a novel mechanism by which HDAC6 activity promotes the transcription of Stat5a target genes and demonstrate utility of HDAC6 inhibition for breast cancer therapy. IMPLICATIONS: HMGN2 deacetylation enhances Stat5a transcriptional activity, thereby regulating prolactin-induced gene transcription and breast cancer growth. Mol Cancer Res; 14(10); 994-1008. (c)2016 AACR. PMID- 27358111 TI - Augmented HR Repair Mediates Acquired Temozolomide Resistance in Glioblastoma. AB - : Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults and is universally fatal. The DNA alkylating agent temozolomide is part of the standard-of-care for GBM. However, these tumors eventually develop therapy driven resistance and inevitably recur. While loss of mismatch repair (MMR) and re-expression of MGMT have been shown to underlie chemoresistance in a fraction of GBMs, resistance mechanisms operating in the remaining GBMs are not well understood. To better understand the molecular basis for therapy-driven temozolomide resistance, mice bearing orthotopic GBM xenografts were subjected to protracted temozolomide treatment, and cell lines were generated from the primary (untreated) and recurrent (temozolomide-treated) tumors. As expected, the cells derived from primary tumors were sensitive to temozolomide, whereas the cells from the recurrent tumors were significantly resistant to the drug. Importantly, the acquired resistance to temozolomide in the recurrent lines was not driven by re-expression of MGMT or loss of MMR but was due to accelerated repair of temozolomide-induced DNA double-strand breaks (DSB). Temozolomide induces DNA replication-associated DSBs that are primarily repaired by the homologous recombination (HR) pathway. Augmented HR appears to underpin temozolomide resistance in the recurrent lines, as these cells were cross-resistant to other agents that induced replication-associated DSBs, exhibited faster resolution of damage-induced Rad51 foci, and displayed higher levels of sister chromatid exchanges (SCE). Furthermore, in light of recent studies demonstrating that CDK1 and CDK2 promote HR, it was found that CDK1/2 inhibitors countered the heightened HR in recurrent tumors and sensitized these therapy-resistant tumor cells to temozolomide. IMPLICATIONS: Augmented HR repair is a novel mechanism underlying acquired temozolomide resistance in GBM, and this raises the possibility of improving the therapeutic response to temozolomide by targeting HR with small molecule inhibitors of CDK1/2. Mol Cancer Res; 14(10); 928-40. (c)2016 AACR. PMID- 27358112 TI - Bone Marrow Microenvironment Niche Regulates miR-221/222 in Acute Lymphoblastic Leukemia. AB - : Acute lymphoblastic leukemia (ALL) has many features in common with normal B cell progenitors, including their ability to respond to diverse signals from the bone marrow microenvironment (BMM) resulting in regulation of cell-cycle progression and survival. Bone marrow-derived cues influence many elements of both steady state hematopoiesis and hematopoietic tumor cell phenotypes through modulation of gene expression. miRNAs are one regulatory class of small noncoding RNAs that have been shown to be increasingly important in diverse settings of malignancy. In the current study, miRNA profiles were globally altered in ALL cells following exposure to primary human bone marrow niche cells, including bone marrow stromal cells (BMSC) and primary human osteoblasts (HOB). Specifically, mature miR-221 and miR-222 transcripts were decreased in ALL cells cocultured with BMSC or HOB, coincident with increased p27 (CDKN1B), a previously validated target. Increased p27 protein in ALL cells exposed to BMSC or HOB is consistent with accumulation of tumor cells in the G0 phase of the cell cycle and resistance to chemotherapy-induced death. Overexpression of miR-221 in ALL cells during BMSC or HOB coculture prompted cell-cycle progression and sensitization of ALL cells to cytotoxic agents, blunting the protective influence of the BMM. These novel observations indicate that BMM regulation of miR-221/222 contributes to marrow niche-supported tumor cell quiescence and survival of residual cells. IMPLICATIONS: Niche-influenced miR-221/222 may define a novel therapeutic target in ALL to be combined with existing cytotoxic agents to more effectively eradicate refractory disease that contributes to relapse. Mol Cancer Res; 14(10); 909-19. (c)2016 AACR. PMID- 27358113 TI - Co-precipitation of DEAE-dextran coated SPIONs: how synthesis conditions affect particle properties, stem cell labelling and MR contrast. AB - Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used as contrast agents for stem cell tracking using magnetic resonance imaging (MRI). The total mass of iron oxide that can be internalised into cells without altering their viability or phenotype is an important criterion for the generation of contrast, with SPIONs designed for efficient labelling of stem cells allowing for an increased sensitivity of detection. Although changes in the ratio of polymer and iron salts in co-precipitation reactions are known to affect the physicochemical properties of SPIONs, particularly core size, the effects of these synthesis conditions on stem cell labelling and magnetic resonance (MR) contrast have not been established. Here, we synthesised a series of cationic SPIONs with very similar hydrodynamic diameters and surface charges, but different polymer content. We have investigated how the amount of polymer in the co-precipitation reaction affects core size and modulates not only the magnetic properties of the SPIONs but also their uptake into stem cells. SPIONs with the largest core size and lowest polymer content presented the highest magnetisation and relaxivity. These particles also had the greatest uptake efficiency without any deleterious effect on either the viability or function of the stem cells. However, for all particles internalised in cells, the T2 and T2* relaxivity was independent of the SPION's core size. Our results indicate that the relative mass of iron taken up by cells is the major determinant of MR contrast generation and suggest that the extent of SPION uptake can be regulated by the amount of polymer used in co precipitation reactions. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27358114 TI - Worldwide burden of gastric cancer in 2010 attributable to high sodium intake in 1990 and predicted attributable burden for 2030 based on exposures in 2010. AB - Assessing the impact that patterns of Na intake may have on gastric cancer will provide a more comprehensive estimation of Na reduction as a primary prevention approach. We aimed to estimate the proportion of gastric cancer cases that are attributable to Na intake above the recommendation by the WHO (<=2 g/d) throughout the world in 2010, as well as expected values for 2030. Population attributable fractions (PAF) were computed for 187 countries, using Na intakes in 1990 and 2010 and estimates of the association between Na intake and gastric cancer, assuming a time lag of 20 years. Median PAF ranged from 10.1% in low to 22.5 % in very high Human Development Index (HDI) countries in men (P<0.001) and from 7.2 to 16.6 %, respectively, among women (P<0.001). An increase in median PAF until 2030 is expected in most settings, except for countries classified as low HDI, in both sexes. High Na intakes account for a large proportion of gastric cancer cases, and proportions are expected to increase in almost all of the countries. Intensified efforts to diminish Na intake in virtually all populations are needed to further reduce gastric cancer burden. PMID- 27358115 TI - A Lamellar Hybrid Assembled from Metal Disulfide Nanowall Arrays Anchored on a Carbon Layer: In Situ Hybridization and Improved Sodium Storage. AB - A lamellar hybrid assembled from metal disulfide (MoS2 , WS2 ) nanowall arrays anchored on nitrogen-doped carbon layers is developed via an in situ hybridization strategy through a synergistic pyrolysis reaction of thiourea and oxometalates. Such a hybrid provides adequate electrical and chemical coupling between the active materials and the carbon substrate, thus realizing a high efficiency electron-conduction/ion-transportation system and exhibiting excellent sodium-storage properties. PMID- 27358116 TI - An overview of the history, applications, advantages, disadvantages and prospects of gene therapy. AB - Gene therapy has become a significant issue in science-related news. The principal concept of gene therapy is an experimental technique that uses genes to treat or prevent disease. Although gene therapy was originally conceived as a way to treat life-threatening disorders (inborn defects, cancers) refractory to conventional treatment, it is now considered for many non?life-threatening conditions, such as those adversely impacting a patient?s quality of life. An extensive range of efficacious vectors, delivery techniques, and approaches for developing gene-based interventions for diseases have evolved in the last decade. The lack of suitable treatment has become a rational basis for extending the scope of gene therapy. The aim of this review is to investigate the general methods by which genes are transferred and to give an overview to clinical applications. Maximizing the potential benefits of gene therapy requires efficient and sustained therapeutic gene expression in target cells, low toxicity, and a high safety profile. Gene therapy has made substantial progress albeit much slower than was initially predicted. This review also describes the basic science associated with many gene therapy vectors and the present progress of gene therapy carried out for various surface disorders and diseases. The conclusion is that, with increased pathobiological understanding and biotechnological improvements, gene therapy will become a standard part of clinical practice. PMID- 27358117 TI - Extracorporeal shockwaves as regenerative therapy in orthopedic traumatology: a narrative review from basic research to clinical practice. AB - Extracorporeal Shock Wave Therapy (ESWT), after its first medical application in the urological field for lithotripsy, nowadays represents a valid therapeutical tool also for many musculoskeletal diseases, as well as for regenerative medicine applications. This is possible thanks to its mechanisms of action, which in the non-urological field are not related to mechanical disruption (as for renal stones), but rather to the capacity, by mechanotransduction, to induce neoangiogenesis, osteogenesis and to improve local tissue trophism, regeneration and remodeling, through stem cell stimulation. On the basis of these biological assumptions, it becomes clear that ESWT can represent a valid therapeutic tool also for all those pathological conditions that derive from musculoskeletal trauma, and are characterized by tissue loss and/or delayed healing and regeneration (mainly bone and skin, but not only). As a safe, repeatable and non?invasive therapy, in many cases it can represent a first?line therapeutic option, as an alternative to surgery (for example, in bone and skin healing disorders), or in combination with some other treatment options. It is hoped that with its use in daily practice also the muscle?skeletal field will grow, not only for standard indications, but also in post?traumatic sequelae, in order to improve recovery and shorten healing time, with undoubted advantages for the patients and lower health service expenses. PMID- 27358118 TI - Headache, migraine and obesity: an overview on plausible links. AB - Headache can represent different disorders with different etiologies; including cardiac, cerebral, vascular, psychiatric, metabolic, neurologic diseases. Recent studies have highlighted that obesity is significantly associated with headache and disability in adults. This rule also applies to children. This review focuses on literature data studying any eventual relationship between headache, migraine and obesity [shown in Body Mass Index (BMI)] in children. Research data have highlighted that there is a relationship between headache physiopathology and central and peripheral mechanisms responsible for food assumption. In this regard, neurotransmitters such as serotonin, and peptides such as orexin and adipocytokines (adiponectin and leptin) seem to play a key role both in food assumption and in headache pathogenesis. These data further emphasize the potential association between headache and BMI. Therefore, those therapeutic strategies aiming to decrease BMI may represent a model of useful treatment to understand whether weight loss reduces the incidence and the severity of headache in obese children. In conclusion, considering the effects of obesity and weight loss on the natural history of headache, important changes are expected in therapeutic management of paediatric headaches. PMID- 27358119 TI - Endocrinology of the skin: intradermal neuroimmune network, a new frontier. AB - Endocrinology systems exert an important effect on vascular function and have direct actions on blood vessels. Estrogens provoke an increase in skin elasticity, epidermal hydration, skin thickness, reduce skin wrinkles and augment the content of collagen and the level of vascularisation. Therefore, there is an intricate cross-talk between skin conditions and stress. In stress, beta2- adrenoreceptor (beta2AR) pathway, cortisol, epinephrine and norepinephrine increase DNA damage and interfere with the regulation of the cell cycle, contributing to aging and skin diseases. Substance P is a neuropeptide released in the skin from the peripheral nerve and is related to stress and inflammation. SP provokes infiltration of inflammatory cells in the skin and induces a variety of cytokines/chemokines. Corticotropin-releasing hormone (CRH), produced by mast cells, is a neuropeptide also expressed in skin and responds to stress. CRH initiates diverse intracellular signaling pathways, including cAMP, protein kinase C, and mitogen-activated protein kinases (MAPK). Under stress, CRH, glucocorticoids, epinephrine and cytokines are generated. Moreover, the release of ACTH binds the receptor MC2-R and stimulates the generation of glucocorticoids such as corticosterone and cortisol, which interact with the transcription factors AP-1 and NF-kB. In skin keratinocytes, ACTH promotes the generation of pro-inflammatory cytokines, which enhances T-cell activity. Cortisol is immunosuppressive by inhibiting Th1 and Th2 cell response, antigen presentation, antibody and cytokine/chemokine production. However, glucocorticoids are certainly helpful in Th1-mediated autoimmune disorders. On the other hand, cytokines, such as TNF, IL-1 and IL-6, stimulate the generation of CRH and activate HPA axis in inflammatory states. Here, we describe for the first time a cross-talk between endocrinology and skin, including pro-inflammatory cytokines and neurogenic inflammatory pathways. PMID- 27358120 TI - Regulatory effect of miRNA on multi-directional differentiation ability of mesenchymal stem cell in treatment of osteoporosis. AB - This study was designed to evaluate the effect of miRNA acting in regulating multi-directional differentiation ability of mesenchymal stem cell in treatment of osteoporosis (OP), with the aim of finding a new idea and approach for clinical treatment of OP. Estrogen deficiency-induced OP mice model was established by means of ovariectomy (OVX). Additionally, a sham group was set up for control. Bone Marrow Mesenchymal Stem Cells (BMMSCs) of OVX group (O/BMMSCs) and BMMSCs of sham group (S/BMMSCs) were separately cultured. Then surface markers of BMMSCs were detected. Multi-directional differentiation ability was identified in the two groups by giving cells targeted induced stimulation. It was found that the bone trabecula, bone density and bone volume fraction of distal femoral metaphysis in the OVX group were much lower than those of the sham group. Moreover, trabecular bone space in the OVX group became larger; O/BMMSCs and S/BMMSCs both had normal expression of surface markers as well as potentials of osteogenic and adipogenic differentiation; O/BMMSCs had a weaker osteogenic capability but a stronger adipogenic capability than S/BMMSCs. All the findings suggest that the regulatory effect of miRNA on multi-directional differentiation ability plays a vital role in the treatment of OP, and there is a close correlation between them; deficiency or functional defect of BMMSCs can result in the occurrence of OP. PMID- 27358121 TI - Targeting leukemic side population cells by isatin derivatives of nicotinic acid amide. AB - Side population (SP) cells mediate chemoresistance in leukemia. However, chemical inhibition approach to target SP cells has been poorly studied. Herein, we report the discovery of isatin derivatives of nicotinic acid amide as potent side population cell inhibitors. The selected derivatives showed superior potency over the reference drug verapamil. Furthermore, the treatment increased chemosensitivity and inhibited the cell proliferation on three different leukemic cell lines, K562, THP-1 and U937, suggesting that both SP and the bulk of leukemic cells are affected. Moreover, treatment with the most potent compound Nic9 reduced the expression of ABCG2, demonstrating that side population inhibition effect of the target derivatives is at least via ABCG2 inhibition. Importantly, the target derivatives induced erythrocyte/dendritic differentiation to leukemic cells mainly through Musashi/Numb pathway modulation. PMID- 27358122 TI - Invasion and metastasis ability of renal cancer cell strains 786-0: under the influence of miR-141. AB - This study aimed to explore the invasion and metastasis ability of miR-141 in 786 0 renal cancer tissue cells, as well as identify the key function of endogenous miR-141 in adjustment and control of malignant activities of renal cancer. The renal cancer cell strain with overexpression of miR-141 and its control renal cancer cell line were constructed; methyl thiazolyl tetrazolium (MTT) assay was adopted to measure proliferation of renal cancer cells; Transwell assay was performed to measure the invasion and metastasis ability of cells; MTT assay and fluorescence activated cell sorting (FACS) were used for measurement of cell apoptosis and drug susceptibility. Results indicated that the expression of miR 141 in 786-0 cells could be significantly increased 400-fold by slow viruses that contained miR-141; moreover, c omprehensive functions showed that miR-141 inhibited the invasion and metastasis ability of renal cancer cells to a great extent (p less than 0.001), partially inhibited cell growth (p less than 0.05) and also induced cell cycle to be arrested in G0/G1 as well as reducing the number of cells in S phase (DNA replicative phase). Moreover, miR-141 could not induce morphologic changes of renal cancer cells, had no direct stimulating effect on cell apoptosis and could not improve the drug susceptibility of renal cancer cells to drugs such as cis-Dichlorodiamineplatinum (DDP), 5-fluorouracil (5-FU) and tumor-related apoptosis-inducing ligand (TRAIL). In conclusion, miR 141 can be considered an important cancer suppressor gene of renal cancer by inhibiting proliferation and metastasis of renal cancer cells. PMID- 27358123 TI - Co-suppression of vitamin C composite nano-drug carrier and its drug delivery to nidus in tumor cells. AB - This study aimed to discuss the co-suppression of vitamin C-contained composite nano-drug carrier and its drug delivery to nidus in tumor cells. Amphiphilic polymers PLA-block-PAAA and block polymer PLA-PEG4000-Maleimide, PLA-block-PAAA and PLA-PEG4000-Maleimide composite nano-micelles were prepared, and, PLA-block PAAA polymer-coated Nile red nano-micelle, PLA-block-PAA and PLA-PEG4000 Maleimide composite nano-micelles as well as paclitaxel-carrying composite nano micelle in different molar ratios were given stability tests. Lastly, PLA-block PAAA and PLA-PEG4000-Maleimide composite nano-micelle cancer cells and paclitaxel carrying composite nano-micelle cancer cells were given toxicity tests. Stability tests showed that self stability of PLA-block-PAAA (63/8) nano-micelle was not sufficient; the stability was good when the molar ratio of PLA-block-PAAA and PLA PEG4000-Maleimide composite nano-micelle was 3:1; paclitaxel-carrying composite nano-micelle had good stability within 48 hours; PAAA segment had an inhibiting effect on C6 cancer cells and paclitaxel-carrying composite nano-micelle had a strong inhibiting effect also on tumors. After 24 hours, with the continuous release of paclitaxel, the tumor inhibiting effect of paclitaxel-carrying composite nano-micelle enhanced gradually, and the controlled-release of drugs had continuous inhibiting effect on tumor cells. Therefore, PAAA segment and paclitaxel had time-postponed synergistic effect. In conclusion, vitamin C contained composite nanometer drug carrier materials can deliver anti-cancer drugs to nidus and thus inhibit tumor cells. PMID- 27358124 TI - Regulatory effect of estrogen receptor-alpha-mediated Wnt/beta-catenin signaling pathway on osteoblast proliferation. AB - This study was designed to investigate the regulatory effect of estrogen receptor alpha (ERalpha)-mediated Wnt/beta-catenin signaling pathway on osteoblast proliferation. Mc3T3-El cells were infected by ERalpha and ERbeta small interfering ribose nucleic acid (siRNA) viruses and treated with estradiol 2 (E2) for 120 min after 24-h infection. Western blot was used to detect expressions of beta-catenin, Gsk 3beta, p-Gsk3beta (Ser9) and CyclinDl; and methyl thiazolyl tetrazolium (MTT) was applied to detect osteoblast proliferation after interference by different ERs. Western blot results indicated that the expressions of beta-catenin, p-Gsk3beta (Ser9) and CyclinDl decreased after ERbeta interference and ERalpha + ERbeta joint interference, and a more obvious decrease was found after the joint interference. After ERbeta interference, beta catenin, p-Gsk3beta (Ser9) and CyclinDl were strongly expressed compared with expressions in the blank control group. MTT results demonstrated that the proliferation rate of osteoblast was lower after the joint interference than after ERbeta interference, while a slight increase was found in the proliferation rate after ERbeta interference in comparison with the blank control group. It can be concluded that estradiol is able to promote the proliferation of osteoblasts in mice by ERalpha-mediated Wnt/beta-catenin signaling pathway. PMID- 27358125 TI - Activation of protein phosphatase 2A is responsible for increased content and inactivation of respiratory chain complex i induced by all-trans retinoic acid in human keratinocytes. AB - This study presents the effect of all-trans retinoic acid (ATRA) on cell growth and respiratory chain complex I in human keratinocyte cultures. Keratinocyte treatment results in increased level of GRIM-19 and other subunits of complex I, in particular of their carbonylated forms, associated with inhibition of its enzymatic activity. The results show that in keratinocytes ATRA-promoted phosphatase activity controls the proteostasis and activity of complex I. PMID- 27358126 TI - Wnt signaling pathway inhibitors as promising diagnostic serum markers of osteolytic bone metastasis. AB - Despite the clinical importance of bone metastases, we still know little about their onset and progression and current diagnostic tools lack the sensitivity and specificity required for clear early diagnosis. We therefore need to continue studying the pathogenesis of bone metastatic invasion in order to improve diagnosis. The Wnt pathway has been described as having an important role in bone carcinogenesis and metastatic progression. This study investigated the diagnostic potential of the two main Wnt inhibitors, sclerostin and DKK-1, to improve the detection of osteolytic bone metastases. We measured sclerostin and DKK-1, MMP-2 and MMP-9, the bone resorption marker TRAP5b and the metastatic marker survivin in a control group of healthy patients, in patients with primary tumors and in a group with metastasis. Sclerostin and DKK-1 were clearly high in primary tumor patients and even higher in metastatic patients, compared to controls. The close correlations with metastatic markers and bone resorption markers make sclerostin and DKK-1 promising as new biomarkers in the diagnosis of bone osteolytic metastases. PMID- 27358127 TI - Hyaluronan scaffold supports osteogenic differentiation of bone marrow concentrate cells. AB - Osteochondral lesions are considered a challenge for orthopedic surgeons. Currently, the treatments available are often unsatisfactory and unable to stimulate tissue regeneration. Tissue engineering offers a new therapeutic strategy, taking into account the role exerted by cells, biomaterial and growth factors in restoring tissue damage. In this light, Mesenchymal Stem Cells (MSCs) have been indicated as a fascinating tool for regenerative medicine thanks to their ability to differentiate into bone, cartilage and adipose tissue. However, in vitro-cultivation of MSCs could be associated with some risks such as de differentiation/reprogramming, infection and contaminations of the cells. To overcome these shortcomings, a new approach is represented by the use of Bone Marrow Concentrate (BMC), that could allow the delivery of cells surrounded by their microenvironment in injured tissue. For this purpose, cells require a tridimensional scaffold that can support their adhesion, proliferation and differentiation. This study is focused on the potentiality of BMC seeded onto a hyaluronan-based scaffold (Hyaff-11) to differentiate into osteogenic lineage. This process depends on the specific interaction between cells derived from bone marrow (surrounded by their niche) and scaffold, that create an environment able to support the regeneration of damaged tissue. The data obtained from the present study demonstrate that BMC grown onto Hyaff-11 are able to differentiate toward osteogenic sense, producing specific osteogenic genes and matrix proteins. PMID- 27358128 TI - Vascular endothelial growth factor and nitric oxide synthase expression in human tooth germ development. AB - Vascular Endothelia Growth Factor (VEGF) and Nitric Oxide Synthase (NOS) expression, were evaluated in human tooth germs at two different stages of embryogenesis, to clarify the role of angiogenesis during tooth tissue differentiation and growth. Seventy-two third molar germ specimens were selected during oral surgery. Thirty-six were in the early stage and 36 in the later stage of tooth development. The samples were evaluated with Semi-quantitative Reverse Transcription-Polymerase chain Reaction analyses (RT-PcR), Western blot analysis (WB) and immunohistochemical analysis. Western blot and immunohistochemical analysis showed a VEGF and NOS 1-2-3 positive reaction in all samples analysed. VEGF high positive decrease reaction was observed in stellate reticulum cells, ameloblast and odontoblast clusters in early stage compared to later stage of tooth germ development. Comparable VEGF expression was observed in endothelial cells of early and advanced stage growth. NOS1 and NOS3 expressions showed a high increased value in stellate reticulum cells, and ameloblast and odontoblast clusters in advanced stage compared to early stage of development. The absence or only moderate positive reaction of NOS2 was detected in all the different tissues. Positive NOS2 expression showed in advanced stage of tissue development compared to early stage. The action of VEGF and NOS molecules are important mediators of angiogenesis during dental tissue development. VEGF high positive expression in stellate reticulum cells in the early stage of tooth development compared to the later stage and the other cell types, suggests a critical role of the stellate reticulum during dental embryo-morphogenesis. PMID- 27358129 TI - The prevalence of Chlamydia pneumoniae in the aortic wall and in peripheral blood of patients scheduled for coronary artery bypass grafting. AB - Some reports confirm a potential role of Chlamydia pneumoniae (ChP) in atherogenesis. In order to explore possible association between ChP and atherosclerosis, investigations were carried out in which the frequency of ChP in the arterial wall and peripheral blood was assessed in a group of patients with chronic coronary artery disease (CAD). Fifty-seven patients were enrolled in the study, 13 women and 44 men aged 61.8+/-6.5 (47-74), with previously diagnosed CAD, scheduled for planned coronary artery bypass grafting due to clinical indications. Vessel specimens retrieved from the ascending aorta (as a part of routine proximal venous graft development procedure) and peripheral blood mononuclear cells (PBMCs) from venous blood were evaluated for the presence of ChP DNA. Genomic DNA was extracted from PBMCs and vessel specimens. Quantitative real-time polymerase chain reaction (qPCR) was performed to detect ChP DNA. A statistically more frequent occurrence of ChP was observed in aortic tissues compared to blood samples (70.2% vs 56.1%, respectively). Similarly, the number of ChP DNA genomic copies [n/1MUg genomic DNA] was significantly higher in tissue specimens compared to blood samples (89+/-91 vs 41+/-77, respectively; p=0.0046). In patients without ChP in blood specimens, we observed significantly higher amounts of ChP in tissue specimens compared to patients with ChP in blood specimens (156+/-71 vs 107+/-88, respectively; p=0.0453). No correlation was found between the number of ChP DNA copies [n/1MUg genomic DNA] in blood and in aortic specimens. The infection of ChP in the aortic wall was connected with hypercholesterolemia (p=0.029) and diabetes (p=0.03). We conclude that Chlamydia pneumoniae is a pathogen frequently occurring in the aortic wall of patients with CAD. The occurrence of ChP DNA in the aortic tissue is related to classic CAD risk factors such as diabetes and dyslipidemia. PMID- 27358130 TI - Articular capsule repair in initial artificial hip replacement via anterolateral approach to the hip joint. AB - This study was carried out to explore articular capsule repair in first artificial hip replacement (AHR) via anterolateral approach and its influence on postoperative dislocation. A total of 292 patients who received AHR via anterolateral approach and had the articular capsule repaired in People?s Hospital of Zhengzhou (Henan, China) from February 2008 to February 2014 were selected and divided into total hip replacement (THR) group (group A1) and artificial femoral head replacement (AFHR) group (group A2). Five hundred and five cases in the control group treated using the same approach but receiving no articular capsule repair were divided into THR group (group B1) and AFHR group (group B2). Condition of postoperative dislocation was compared between the two groups. All cases were followed up for 6 months to 5 years (average: 3.75 years); it was noted that the difference in average age, gender, disease constitution and follow-up time in the two groups was not significant (P>0.05). Moreover, groups A1 and B1 were found with 1 case of early hip joint dislocation (0.73%) and 13 cases of hip joint dislocation (5.24%) respectively post-operatively, and the comparison between the two groups was statistically significant (P less than 0.05). One case of hip joint dislocation (0.65%) was found in group A2 and 5 cases (1.95%) in group B2 in early post operation and the difference between two groups had no statistical significance (P>0.05). Neither the repair group nor the control group developed late-onset dislocation after the operation. Thus, we can state that articular capsule repair is feasible during the first AHR via anterolateral approach, which decreases the occurrence of early hip joint dislocation after operation and proves that repairing articular capsule during AFHR via anterolateral approach is unnecessary. PMID- 27358131 TI - Psychological stress moderates the relationship between running volume and CD4+ T cell subpopulations. AB - Endurance-based exercise training can lead to alterations in components of the immune system, but it is unknown how psychological stress (another potent immunomodulator) may impact these changes. The purpose of this study was to determine the moderating role of psychological stress on exercise-induced immune changes. Twenty-nine recreational runners were recruited for this study four weeks before completing a marathon. Each subject reported: weekly training volume (miles/wk) for the week prior to the study visit; completed the Perceived Stress Scale (PSS), the state version of the State-Trait Anxiety Inventory (STAI) and the Penn State Worry Questionnaire (PSWQ); and donated blood for assessment of CD4+ T cell subpopulations and mitogen-induced cytokine production. Participants ran an average of 30 (+/-13.4) miles (1 mile=1.6 km) per week. Average values (SD) for immune biomarkers were: regulatory T cells (Treg), 3.2% (+/-1.2%); type 1 regulatory cells (Tr1), 27.1% (+/-8.3%); T helper 3 (Th3), 1.8% (+/-0.7%); interferon gamma (IFNgamma), 3.1 pg/ml (+/-1.0); interleukin (IL)-4, 1.4 pg/ml (+/-1.1); IFNgamma/IL-4, 8.6 (+/-1.2); IL-10, 512 pg/ml (+/-288). There was a significant relationship between running volume and both Treg cell numbers (slope of the regression line (beta)=0.05, p less than 0.001) and IL-10 production beta= 10.6, p=0.002), and there was a trending relationship between running volume and Tr1 cell numbers (beta=-0.2%, p=0.064). Perceived stress was a trending moderator of the running volume-Treg relationship, whereas worry was a significant moderator of the running volume-IFNgamma and running volume-IFNgamma/IL-4 relationships. These data indicate that various forms of psychological stress can impact endurance exercise-based changes in certain immune biomarkers. These changes may reflect an increased susceptibility to clinical risks in some individuals. PMID- 27358132 TI - Assessment of magnesium influence on fatty acid content in isolated rat hepatocytes subjected to incubation. AB - Magnesium salts are components of many dietary supplements used in treatment or prevention of magnesium deficiency. Hypomagnesemia usually results from an improper lifestyle, including unbalanced diet. Isolated hepatocytes of animals or humans are the preferred model used to study the in vitro effects of exogenous factors on cellular metabolic changes. The aim of this study was to evaluate the content of saturated, monounsaturated and polyunsaturated fatty acids and their esters in isolated rat hepatocytes influenced by different magnesium concentrations. The isolated rat hepatocytes were used as the test material. Hepatocytes were prepared in culture medium (Hepatocyte Medium) + MgCl(2) solution to concentrations of 2 mM/dm(3) MgCl(2), 4 mM/dm(3) MgCl(2). After incubation with different concentrations of magnesium ions, changes in the content of fatty acids and their esters were found for the whole hepatocytes and hepatocyte membranes. Despite changes in the fatty acid content in the whole hepatocytes and their membranes, there were no changes in the coefficient of degree of saturation of fatty acids when different concentrations of MgCl2 were used. PMID- 27358133 TI - Insulin pump for the treatment of diabetes in combination with ulcerative foot infections. AB - Ulcerative foot infection is a chronic complication frequently seen in diabetic patients, and can result in disability. To evaluate insulin pump treatment for type 2 diabetes in combination with ulcerative foot infection, we selected 168 diabetic patients who developed foot ulcers and received treatment from April 2012 to April 2014 in the People?s Hospital of Zhengzhou, Henan, China. The patients were divided into a treatment group and a control group, 84 in each group. Besides anti-infection treatment, patients in the control group were given multiple subcutaneous insulin injection (MSII), while patients in the treatment group were given continuous subcutaneous insulin infusion (CSII). Ulcer area, fasting plasma glucose (FPG), C-reactive protein (CRP) and count of white blood cells (WBC) were recorded before treatment, one week after treatment, two weeks after treatment and four weeks after treatment; moreover, ulcer healing condition was recorded four weeks after treatment and the related factors were analyzed. Patients in the treatment group showed an obviously narrowed ulcer area two and four weeks after treatment (P less than 0.05) and significantly lowered levels of FPG, CRP and WBC in the 1st, 2nd and 3rd weeks after treatment (P less than 0.05); four weeks after treatment, 88.1% of patients in the treatment group and 66.7% in the control group had healed well, and the difference between two groups was statistically significant (chi2=5.509, P=0.019). Multi-factor logistic regression analysis indicated that levels of FPG, CRP and WBC at baseline and four weeks after treatment had a positive correlation to ulcer healing (P less than 0.05). All the above findings suggest that insulin pump can improve ulcer healing of patients suffering from diabetic foot ulcers as it effectively controls blood glucose level, restrains inflammatory reaction and prevents spreading of infection. PMID- 27358134 TI - Continuous plasma filtration adsorption in treatment of severe infection-induced multiple organ dysfunction syndrome. AB - Multiple organ dysfunction syndrome (MODS), a high-risk disease, has a fatality rate of 70%. To improve treatment of this disease, in recent years many scholars have explored the pathological and physiological changes of MODS. To observe the curative effect of continuous plasma filtration adsorption (CPFA) in the treatment of MODS, we selected 96 patients who were diagnosed with severe infection-induced MODS and were treated in the First Affiliated Hospital of Zhengzhou University between February 2012 and October 2014 and divided them into an observation group and a control group. Besides conventional treatment, the observation group was also given CFPA in combination with high volume hemofiltration (HVHF), while the control group only received HVHF. Changes of blood routine index, balance of electrolyte and acid-base as well as vital signs were observed before and after treatment. Also, blood, kidney and blood gas were examined. For all patients, tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and C-reactive protein (CRP) were recorded at the start of treatment (0 h), and 5 h and 10 h after treatment. It was found that both therapies could lower blood urea nitrogen (BUN) and creatinine levels and maintain balance of electrolyte and acid-base, but had no obvious influence on leukocyte, blood platelet and hematocrit. In the observation group, PaO(2)/FiO(2) and mean arterial pressure (MAP) were significantly improved after surgery (P less than 0.05), while Acute Physiology and Chronic Health Evaluation (APACHE) II score had an obvious decrease (P less than 0.05). In contrast, the control group was observed with insignificantly changed PaO(2)/FiO(2), MAP and APACHE II score (P>0.05). TNF-alpha, IL-6 and CRP levels of the two groups had no statistically significant difference at the start of treatment (P>0.05), but TNF-alpha, IL-6 and CRP levels of the observation group became remarkably lower than those of the control group 5 h and 10 h after treatment (P less than 0.05). Therefore, CPFA is proved to be safe and effective in treating patients with severe infection induced MODS as it can lower the level of proinflammatory cytokines and improve the level of anti-inflammatory cytokines; thus, it is worthy of clinical promotion. PMID- 27358135 TI - Vena-venous hemofiltration in treating severe injury-induced multiple organ dysfunction syndrome. AB - Severe multiple injury (SMI) can induce multiple organ dysfunction syndrome (MODS) and easily result in complications, as well as having a high mortality rate. To explore the curative effect of continuous vena-venous hemofiltration (CVVH) in treating MODS and its effect on serum tumor necrosis factor (TNF)-alpha interleukin (IL)-10 and nitric oxide (NO), we selected 200 patients who suffered from SMI and received treatment in the First Affiliated Hospital of Zhengzhou University between April 2012 and April 2014 as research subjects. All patients were treated with CVVH. Vital signs, blood oxygen pressure (PaO(2)) and oxygenation index (OI) of artery, electrolyte and acid-base balance were observed before and after treatment. Before treatment, 1 h and 12 h after the start of treatment, and at the end of treatment, TNF-alpha and IL-10 concentrations in serum and ultrafiltrate were tested using enzyme linked immunosorbent assay, and NO concentration in serum and ultrafiltrate was detected using nitrate reduction method. After treatment, heart rate and respiratory rate of patients had significant decline (P less than 0.05) and average arterial pressure rose remarkably (P less than 0.05); blood urea nitrogen and creatinine decreased (P less than 0.05 or 0.01); PaO(2) and OI were both significantly increased (P less than 0.01); hyperkalemia and acidosis were effectively corrected (P less than 0.01); but differences of Na+, Ca2+ and Cl- before and after treatment had no statistical significance (P>0.05). Serum IL-10 concentration had a significant increase after treatment, while TNF-alpha and NO concentrations had a significant decline after treatment. A small quantity of IL-10, but not of TNF-alpha, was detected from ultrafiltrate. Concentration of NO in ultrafiltrate was higher. It can be concluded that CVVH can effectively relieve clinical symptoms of MODS patients, improve function of organs, correct electrolyte disturbance and acid base imbalance and eliminate TNF-alpha and NO in serum, which is effective in improving the ratio of successful rescue of patients developing MODS. PMID- 27358136 TI - BLCA-4 and UBC combined detection for early diagnosis of bladder cancer. AB - The objective of the present study was to report the clinical significance of bladder cancer specific nuclear matrix protein 4 (BLCA-4) and urinary bladder cancer (UBC) on early diagnosis of bladder cancers. Enzyme-linked immunosorbent assay (ELISA) was used to detect BLCA-4 and UBC of 56 bladder cancer patients and 26 patients with urinary tract benign diseases, serving as controls. Urine exfoliated cell test was performed, and then the significance of BLCA-4 and UBC on the diagnosis of bladder cancers was analyzed. The sensitivity of BLCA-4 and UBC of the bladder cancer patients was significantly higher than that of the urine exfoliated cell test (P less than 0.05). The difference of BLCA-4 and UBC was not significant (P >0.05). The difference of BLCA-4 and UBC in the tumors with different gradings and stagings was not significant (P >0.05). Combined detection of BLCA-4 and UBC could improve the diagnosis sensitivity and specificity of bladder cancers with the advantages of high maneuverability, repeatability and objective results. PMID- 27358137 TI - Thrombin in combination with intensive nursing in treating upper gastrointestinal bleeding in children. AB - Pediatric upper gastrointestinal bleeding, a commonly seen pediatric emergency, needs timely symptomatic treatment to avoid a worse outcome. To discuss the clinical effect of thrombin treatment in combination with intensive nursing on pediatric upper gastrointestinal bleeding, this study analyzed 128 children who were treated in the second ward of the Children?s Internal Medical Department in the First Affiliated Hospital of Zhengzhou University between February 2012 and December 2014. The patients were divided into two groups, an experimental group and a control group. Besides thrombin, the experimental group was given intensive nursing, consisting of regular nursing and targeted nursing, while the control group was given regular nursing only. Clinical indexes of the two groups, such as effective rate, nursing satisfaction and side effect rate, were compared. Relevant clinical indexes such as duration of hospital stay, time to stopping of bleeding and Self-Rating Anxiety Scale (SAS) score, as well as overall satisfaction level of the observation group were all better than those of the control group and differences between the two groups had statistical significance (P less than 0.05). Furthermore, difference of overall effective rate between the experimental group (90.63%) and the control group (68.75%) was significant. Difference of incidence of side effects between the two groups was statistically significant. Thus thrombin treatment in combination with intensive nursing proved to have a remarkable clinical effect and high safety level in treating pediatric upper gastrointestinal bleeding and, moreover, it shortens treatment time and enhances the patients? quality of life. PMID- 27358138 TI - Elevated expression of runt-related transcription factors in human abdominal aortic aneurysm. AB - Abdominal aortic aneurysm (AAA) is a multifactorial disease of unknown etiology. AAA is caused by segmental weakening of the aortic walls and progressive aortic dilation leading to the eventual rupture of the aorta, accompanied by intense inflammation. Additionally, studies have indicated a close relationship between the pathogenesis and progression of AAA and cellular immune responses in aneurysm wall tissue. The Runt-related genes (RUNX) encode multifunctional mediators of the of intracellular signal transduction pathways in vascular remodeling, endothelial function, immune response and inflammation. The aim of this study was to evaluate the expression level of RUNX regulatory genes in AAA tissues and to assess the correlations between them. The study was performed on AAA wall-tissue samples obtained from patients with AAA during open aneurysm repair and normal aortic tissues collected from healthy organ donors. There are no proven clinical management strategies or pharmaco-therapeutics to prevent AAA progression once an AAA has been detected. Moreover, so far no biomarkers have been established to indicate the disease status of AAA. Hence, understanding the pathogenesis of AAA has recently become an increasing priority in basic and translational vascular research. We identified significantly higher mRNA and protein level of all of three Runt-related genes in aneurysmal aorta compared to a normal aorta. Increased expression of RUNX2 was demonstrated for the first time in abdominal aortic aneurysm tissue. Additionally, relationships between the activity of RUNX genes in the pathological tissue were identified. The results of elevated expression of RUNX genes and their relationships in the AAA tissues suggest the involvement of conserved Runt-related genes in the pathophysiology of AAA development. PMID- 27358139 TI - Effect of embolic microspheres in the treatment of primary hepatic carcinoma. AB - The purpose of this study was to evaluate the clinical effect of embolic microspheres in the treatment of primary hepatic carcinoma. Fifty-eight patients who were confirmed with primary hepatic carcinoma by imaging were retrospectively analyzed. They were firstly perfused with 50 mg of oxaliplatin and 40 mg of epirubicin. Embolic microspheres were then injected into the distal end of targeted blood vessels. After this procedure, dynamic observation was carried out until tumor stain disappeared. Liver function and blood indexes were reexamined on days 5, 6, 7 and 28 after treatment, and moreover, the liver was examined with Magnetic Resonance Imaging (MRI) or computed tomography (CT). Compared to traditional lipiodol embolization, embolic microspheres did not aggregate the damage on liver function and the imaging examination suggested necrosis of some tumor tissues. Embolic microspheres proved to be effective in treating primary hepatic carcinoma. It produces no damage on liver function and can lead to significant shrinkage of hepatic carcinoma and necrosis of some tumor tissues. Embolic microspheres, which merely block distal branches of tumor-feeding artery, can avoid collateral circulation induced by permanent blocking, thus achieve a good treatment effect. PMID- 27358140 TI - Computed tomography diagnosis of neonatal hypoxic ischemic encephalopathy combined with intracranial hemorrhage and clinical nursing treatment. AB - Hypoxic ischemic encephalopathy (HIE), one of the common causes of newborn invalidism, is likely to induce nervous system-associated sequelae and even intracranial hemorrhage in severe cases. The incidence rate of HIE has been rising in recent years. In order to study the clinical nursing effect for HIE combined with intracranial hemorrhage, 76 newborns diagnosed with HIE combined with intracranial hemorrhage by spiral computed tomography (CT) from the of Binzhou People?s Hospital, Shandong, China were selected. They were divided into a control group and an intervention group. The control group received routine nursing, while the intervention group received comprehensive nursing intervention. The experimental results suggested that the mental developmental index (MDI) value and the psychomotor developmental index (PDI) value of patients in the intervention group were much higher than those of the control group and the difference was significant (p<0.05). The curative effect of the intervention group was remarkably better than that of the control group and the difference was also statistically significant (p less than 0.05). Moreover, the intervention group had a lower incidence rate of untoward reactions. All the findings suggest that comprehensive nursing intervention can help newborns diagnosed with HIE combined with intracranial hemorrhage recover more effectively, therefore is worth applying. PMID- 27358141 TI - Changes in phagocytosis and expression of microglial cells in craniocerebral injury mice models. AB - The objective of this study was to investigate the changes in phagocytic function and expression quantities of CD11b and tumor necrosis factor-alpha (TNF-alpha) among microglia cells of craniocerebral injury mice. Modified Feeney method was used to establish the craniocerebral injury mice models. Twenty-one male SPF mice were divided into a control group and a trauma group. The scalp was incised and a bone window was opened in the control group without cerebral injury. In the trauma group, the mice were sacrificed after the craniocerebral injury at 1, 3, 6, 12, 24 and 48 h to make frozen sections of cerebral tissues. The phagocytic rate of microglia cells was observed by using fluorescent microsphere. The changes in the expression quantities of CD11b and TNF-alpha were detected by enzyme-linked immuno sorbent assay (ELISA). The phagocytic ability of the microglia cells after the craniocerebral injury increased at 1 h after injury compared with that of the control group (P less than 0.01). The expression of surface antigen CD11b of the microglia cells and the expression of TNF-alpha increased at 1, 3, 6, 12, 24 and 48 h after the injury compared with those of the control group (P less than 0.01). The phagocytic ability of the microglia cells increased. The expressions of CD11b and TNF-alpha were also gradually enhanced in the acute phase after craniocerebral injury, and then gradually decreased to the normal level. The expressions of CD11b and TNF-alpha indicated a high consistency with the changing trend of the phagocytic ability, suggesting that the microglia cells may participate in the regulation of the inflammatory process of the central nervous system through absorbing apoptotic cells and increasing and secreting inflammatory and anti-inflammatory factors. PMID- 27358142 TI - Lactulose oral solution for the treatment of postpartum constipation. AB - The purpose of this study is to explore the effectiveness and safety of lactulose oral solution in treating puerperal constipation. The lactulose group was given lactulose, 15 ml once a day, and then given a maintenance dose of 5 ~ 15 ml/time according to defecation condition of patients. Maintenance treatment lasted for one week if the symptoms were relieved; but once symptoms recurred, the medication was restored. Patients in the control group were blank controls. The treatment lasted for six weeks. The conditions of patients, adverse events and combined medication were recorded every day. Patients were evaluated with SF-36 scale before and after treatment. Two hundred and eleven patients with postpartum constipation were selected from five research institutes and they were divided into lactulose group (n=106) and control group (n=105). The curative effect and the improvement of symptoms of the lactulose group were much better than those of the control group (p less than 0.01). Constipation in the lactulose group relieved faster compared to the control group (p less than 0.05). Number of days without constipation in the lactulose group was much more than that of the control group (p less than 0.05). Defecation time in the lactulose group was shorter than that of the control group (p less than 0.05). Dose of lactulose in the lactulose group reduced week by week. Differences of general physical conditions in SF-36 scale between two groups were statistically significant (p less than 0.05). Various vital signs of the two groups had no significant changes after treatment. It can be concluded that, lactulose is an effective and safe drug for treating postpartum constipation. PMID- 27358143 TI - Effect of OPCML gene on the biological behavior of gastric cancer cell line AGS. AB - The objective of this investigation was to explore the association of OPCML with gastric cancer and its clinical significance. The expression of OPCML was detected by immunohistochemistry in 118 cases of gastric carcinoma. The OPCML expression in the normal tissues and 7 kinds of gastric cells was assessed by RT PCR. The recombinant plasmid pcDNA3.1-OPCML was constructed and transfected into AGS cells. CCK8 and colony formation assay were employed to analyze the effect of OPCML on AGS. Immunohistochemistry results showed that the expression of OPCML in gastric cancer was 68.6% and the expression of OPCML was negatively correlated with the depth of tumor invasion and tumor differentiation degree (P < 005); OPCML expression, depth of tumor invasion, lymph node metastasis and distant metastasis were important factors affecting the prognosis of the survival of the patients (P <0.05). OPCML m-RNA expression in the gastric cancer cells was significantly lower than that in the normal gastric mucosa. RT-PCR showed that the expression of OPCML was aberrantly increased in the cells transfected with pcDNA3.1-OPCML. CCK8 and colony formation assay showed that OPCML significantly inhibited the growth, proliferation, and colony formation of the AGS cells. OPCML plays an important role in gastric cancer, and may be a new prognostic indicator of gastric cancer. PMID- 27358144 TI - Effect of X-ray irradiation on epithelial-mesenchymal transition of colorectal cancer SW480 cells. AB - This study was carried out to explore the effect of X-ray irradiation on epithelial-mesenchymal transition (EMT) of colorectal cancer SW480 cells. Human colorectal cancer SW480 cells used in this study were irradiated by X-rays in 0 Gy, 4 Gy and 8 Gy doses, respectively. Transwell method was adopted to detect the changes of invasion and migration ability of SW480 cells cultured for 24 h after being irradiated by X-rays in 0 Gy, 4 Gy and 8 Gy doses. After X-ray irradiation, invasion ability of cells in 4 Gy dose group and 8 Gy dose group strengthened significantly compared with that of the 0 Gy dose group (p < 0.05); invasion ability of cells in 8 Gy dose group also strengthened significantly compared to the 4 Gy dose group (p < 0.05). After X-ray irradiation, migration ability of cells also changed: migration ability of cells in 4 Gy dose group and 8 Gy dose group strengthened significantly compared with that of the 0 Gy group (p less than 0.05). Results of QRT-RCR and Western blot detection showed that after X-ray irradiation, the expression of epithelial index E-cadherin in 4 Gy dose group and 8 Gy dose group decreased significantly compared with that of the 0 Gy dose group (p < 0.05); moreover, the higher the dose was, the more significantly the expression decreased. Therefore, X-ray irradiation-induced EMT is in positive correlation with the irradiation dose to some extent. Besides, X-ray irradiation can enhance the invasion and migration ability of human colorectal cancer cells. PMID- 27358145 TI - Reactivity of patients with maintenance hemodialysis to erythropoietin in the treatment of renal anemia. AB - To explore the reactivity of patients with renal anemia (MHD) to erythropoietin (EPO) in maintenance hemodialysis (HD), 31 patients were enrolled in this study. According to the level of serum ferritin (SF), they were divided into two groups; one group received treatment using recombinant human erythropoietin (rHuEPO) and the other group was given iron sucrose. Taking terminal EPO dosage, terminal erythropoietin resistance index (ERI) and rate of change of ERI (DeltaERII) as target indexes, the influence of SF level on dosage of EPO was evaluated after usage conditions of relevant substances in a 3-month period. The results revealed that differences of dialysis age, albumin (ALB), blood calcium, initial and terminal SF, variable quantity of hemoglobin (Hb), terminal EPO and ERI between two groups had statistical significance. Furthermore, SF level and terminal EPO (r = -0.37, P < 0. 05) as well as SF level and terminal ERI (r = - 0.39, P <0.05) were negatively correlated. Difference of terminal ERI between the two groups had statistical significance. It can therefore be summarized that supplementing an iron agent intravenously to maintain SF level between 500 ng/ml and 1200 ng/ml may improve reactivity of patients with MHD to EPO. In addition, rHuEPO therapy in treating anemia of patients with MHD has the same effect with intravenous drug delivery, less side effects and is easy to administer. PMID- 27358146 TI - Role of anti-inflammatory cytokines in pathogenesis of pediatric mycoplasma pneumoniae pneumonia. AB - Through detection and analysis of the changes of interleukin (IL)-2 and IL-10 in children with mycoplasma pneumoniae pneumonia (MPP), this study aimed to explore the role of cytokines in the pathogenesis of pediatric MPP as well as immunological pathogenesis of MPP, to provide guidance for clinical diagnosis, assessment and treatment of MPP. Enzyme linked immunosorbent adsorption (ELISA) analysis was applied to determine the expression level of IL-2 and IL-10 in serum. According to the experimental results, we found that the expression levels of IL-2 and IL-10 changed significantly in different phases of MPP in comparison with a healthy control group and a case control group. The expression levels of IL-2 and IL-10 can be used as an important indicator for early diagnosis of MPP. Accordingly, detection of IL-2 and IL-10 is of great significance to the diagnosis of MPP and studies on their roles can provide guidance for treatment. PMID- 27358147 TI - Flow cytometer analysis of cell apoptosis of endometrial carcinoma with Wnt10b. AB - The aim of this study is to analyze the cell apoptosis of endometrial carcinoma (EC) with Wnt10b by Fluorescence Activated Cell Sorting (FACS) technology. AN3CA cell lines and Ishikawa-H-12 cell lines were taken as the in-vitro cell models to observe the influence of Wnt10b on key factors of Wnt signal pathway. Methyl thiazolyl tetrazolium (MTT) was applied for the detection of cell proliferation while FACS was used for the detection of cell apoptosis. Data were analyzed using statistical software SPSS14.0. After the overexpression of Wntl0b in AN3CA cells, the apoptosis rate dropped significantly compared with the two control groups (p < 0.05); while the apoptosis rate increased significantly compared with the control groups (p < 0.01) after Wntl0b knock-off in Ishikawa3-H-12 cells. In normal endometrium, Wnt10b gene expression was negative, while that in EC cells was positive. It can be concluded that Wnt10b gene can promote EC cell proliferation and inhibit its apoptosis. PMID- 27358148 TI - Correlation between IL-6 and invasiveness of ectoderm cells of embryo in early pregnancy. AB - This study aimed to explore the correlation between Interleukin-6 (IL-6) and invasiveness of ectoderm cells of embryo in early pregnancy, in order to further discuss whether IL-6 can enhance invasiveness of ectoderm cells. The study lays the foundation for determination of pathogenesis of some gestation period-related diseases. Differences in mRNA and protein expression of trophoblastic cell line JEG-3 cells in IL-6, matrix metalloproteinase-2 (MMP-2) and MMP-9 were analyzed; the regulating effect of different concentrations of IL-6 on invasive ability of trophoblast cells was studied by Transwell assay; the effect of IL-6 on proliferation of ectodermal cell line JEG-3 of embryo was analyzed by methyl thiazolyl tetrazolium (MTT) assay. The invasive number of JEG-3 cells incubated by IL-6 (10 ng/ml) was higher than that of the control group, and the difference had statistical significance (p < 0.05). Results of using MMT assay to detect the effect of IL-6 on proliferation of trophoblastic cell line JEG-3 showed that JEG 3 cells before and after processing had no significant difference from the control group (p >0.05). Therefore, IL-6 can enhance invasiveness of ectoderm cells of embryo through activation of MMP-2. PMID- 27358149 TI - Mechanism of age-related changes of bone marrow mesenchymal stem cells in senile osteoporosis. AB - This study was carried out to explore the age-related changes of bone marrow mesenchymal stem cells (BMMSCs) in mice as well as the influence of autophagy on the age-related changes of BMMSCs. BMMSCs aging-associated protein acetylation P53, P21 and P16 expressions in young and senile mice, protein expression of telomerase reverse transcriptase (TERT) as well as reactive oxygen species (ROS) level were detected and compared; the expression of BMMSCs autophagy associated gene, autophagy related protein molecule and LC3 molecule were detected; the influence of differently concentrated rapamycin and 3-MA on BMMSCs autophagy level was observed to select effective concentrations; the influence of rapamycin and 3-MA on BMMSCs cell cycle-related gene expression, apoptosis related gene expression and ROS level were discussed. Results revealed that the senile BMMSCs group had higher acetylation P53, P21 and P16 expression and fluorescence intensity than the young group, but its TERT expression, Beclin1 and LC3 gene expression and fluorescence intensity were lower than the young group. Both rapamycin and 3-MA inhibited CyclinD1 (CCND1) and CyclinD2 (CCND2) expression. Rapamycin promoted the expression of apoptosis-related genes Caspase3 and Caspase8 in the senile group, while 3-MA inhibited them in both the young and senile groups. It can therefore be concluded that senile BMMSCs have multiple age related changes, performing as decrease of osteogenic capability and multiplication capacity, increase of acetylation P53, P21 and P16 protein expression, apoptosis and ROS level as well as decrease of telomerase activity. Furthermore, the autophagy level in senile BMMSCs reduced compared with young cells; autophagy activation can decrease ROS level and autophagy suppression improves ROS level; and autophagy regulation affects cell cycle and apoptosis. PMID- 27358150 TI - Multicenter study of autoverification methods of hematology analysis. AB - This study was designed to establish and validate a set of autoverification methods for hematology analysis. One thousand and twenty-four samples were selected from Shanghai Ruijin Hospital and 999 from Beijing Hospital, China. False positive, false negative and autoverification pass rates were verified and the rules were then adjusted and confirmed according to the verification results. After confirmation, at least 10,000 sample cases were selected from Shanghai Ruijin Hospital, Beijing Hospital and China Armed Police General Hospital and checked automatically. The differences in the autoverification pass rate and average report delivery time before and after the application of the autoverification methods were compared between the three hospitals. Preliminary validation results showed that the false negative rates of the Shanghai Ruijin Hospital and Beijing Hospital were less than 2%. The false positive rates of these two hospitals were high, close to 18%. After rule adjustment, the false negative rate was basically the same as before adjustment, but the false positive rate declined obviously while the pass rate of autoverification improved significantly. The autoverification pass rates of the three hospitals were 76.4%, 85.1% and 84.2%, respectively. The turnover time (TAT, time from receipt of sample to report of the result) of the three hospitals decreased by 4.1 min, 8.8 min and 10.2 min, respectively. Autoverification systems using a Mindray BC-6800 auto hematology analyzer and labXpert were confirmed as being effective in reducing TAT and enhancing working efficiency on the premise of ensuring low false negative rate. PMID- 27358151 TI - Efficacy and safety of omalizumab in paediatric age: an update of literature data. AB - Immunoglobulin E (IgE) was discovered in 1966 and was found responsible for immune defense against helminths, type I hypersensitivity and allergic diseases. IgE mediates allergic responses by binding to Fc receptors (the high affinity Fc epsilon receptor I and the low affinity Fc-epsilon receptor II or CD23) expressed on tissue mast cells and blood basophils. This binding leads to degranulation and release of pro-inflammatory mediators. Considering the pivotal role of IgE in allergic diseases, antibodies against IgE potentiate an array of new therapeutic strategies and in this regard omalizumab (rhuMAb-E25, Xolair) has been developed as a monoclonal biologic drug to block serum IgEs. Although the use of omalizumab has been studied vigorously in many adult populations with allergic diseases, there are few heterogenous studies on children. There are very few ongoing clinical trials with omalizumab exclusively on children, although some adult studies have concluded pediatric patients as a part of their studies. Nevertheless, in pediatric clinical trials omalizumab has been demonstrated to be effective and safe also in this age group. Herein, the authors present a systematic review of extensive literature data on the use of omalizumab in children and adolescents. PMID- 27358152 TI - Pneumomediastinum, subcutaneous emphysema and pneumorrhachis in asthmatic children. AB - Pneumomediastinum (PM), subcutaneous emphysema (SE) and pneumorrhachis (also known as epidural air (EDA) or epidural emphysema) are very rare findings in children. PM is defined as the passage of air from intra-alveolar space to interstitium and, later, to the mediastinum. From the mediastinum, the air may catch up subcutaneous tissue (usually of the neck) and/or epidural space via the cervical fascial planes and neural foramina, forming respectively SE and EDA. The PM can be divided in spontaneous (or idiopathic) and secondary PM. Only few studies have evaluated the exact incidence of PM and its complications in children, and to define the correct diagnostic work up, treatment and outpatient follow-up. We report the case of a 9-year-old child with undiagnosed asthma that, during severe asthmatic flare secondary to acute infection of high airway, developed PM, SE and EDA. PMID- 27358153 TI - An unusual case of mammary Paget?s disease in a woman with psoriasis. AB - Mammary Paget?s disease (MPD) is a malignant breast tumor, which is characterized by intraepidermal infiltration from malignant glandular epithelial cells. Often it may include an underlying ductal carcinoma in situ or an invasive ductal carcinoma. Clinically it appears as an erythematous patch, moist or crusted, with or without desquamation that in some cases becomes ulcerated, causing infiltration and inversion of the nipple. We report the clinical case of a 60 year-old woman, treated in our department for psoriasis, presenting with erythema of nipple and areola with nipple erosion, ulceration and poor secretion. Suspecting Paget?s disease of the nipple, radiological exams (mammography and breast MRI) were performed. A biopsy for histological examination was carried out and confirmed the diagnosis of mammary Paget?s disease. MPD is sometimes difficult to diagnose both clinically and radiologically, therefore it is important to distinguish from other conditions: in literature MPD is reported in differential diagnosis with psoriasis given its similar clinical features, and in some cases MPD has been treated with topical and systemic steroids due to a wrong diagnosis. However, the concomitance, in the same individual, of mammary Paget?s disease and psoriasis has never been described. PMID- 27358154 TI - Efficacy and tolerability of a combined lipid-lowering nutraceutical on cholesterolemia, hs-CRP level and endothelial function in moderately hypercholesterolemic subjects. AB - Our aim was to test, by a double-blind, placebo-controlled randomized clinical trial, whether a short-term treatment with a combined lipid-lowering nutraceutical could improve endothelial function in a cohort of moderately hypercholesterolemic subjects. Thus, 80 healthy, moderately hypercholesterolemic subjects were consecutively enrolled and, after 4 weeks of stabilization diet, they were randomized to either the tested lipid-lowering nutraceutical or placebo for 8 weeks. At the beginning and end of treatment a complete lipid pattern, safety parameters, hs-CRP and endothelial function were measured. When compared to placebo, during nutraceutical treatment patients experienced a more favorable percentage change in total cholesterol (TC vs baseline: -17.9%; TC vs placebo: 5.6%), LDL-cholesterol (LDL-C vs baseline: -23.3%; LDL-C vs placebo: -2.8%), hs CRP (hs-CRP vs baseline: -2.4%; hs-CRP vs placebo: -1.5%), and endothelial function (pulse volume displacement vs baseline: +17%; pulse volume displacement vs placebo treatment: -3.3%). No significant difference was observed in respect to effects on triglycerides, HDL-cholesterol and safety parameters. On the basis of our data, the tested lipid-lowering nutraceutical seems to significantly improve endothelial function in moderately hypercholesterolemic subjects. These results have to be confirmed on larger patient samples and over longer periods. PMID- 27358155 TI - Does cyclic guanosine monophosphate induce autophagy in thyroid malignant carcinoma through down-regulation of cyclic guanosine monophosphate phosphodiesterase? AB - The aim of this study was to evaluate whether or not the expression of cGMP- phosphodiesterases (cGMP-PDE) varies in different thyroid pathologies and to elucidate the relationship between the expression of cGMP-PDE, cGMP, and autophagy. Fifty-four thyroid biopsy samples, excised to perform the biopsy, were split into two parts and randomly assigned: one part was microscopically examined and histological classified, and the other was frozen and analysed in order to evaluate the cGMP-PDE activity. Intracellular cGMP was also measured. A strong expression of intracellular cGMP and cGMP-PDE activity was observed in carcinoma in respect to controls and benign pathologies. The level of cGMP-PDE in papillary carcinoma without lymph node involvement (N-) was approximately four-fold higher compared to those with lymph node invasion (N+/-). On the contrary, the cGMP was one and a half times higher in N+/- than N-. Our results are promising, although further epigenetical studies are needed to confirm this association. A correlation between the cGMP-degrading activity and the severity of thyroid pathology has been shown. The decrease of cGMP-PDE and the increase of cGMP in N+/- papillar carcinoma could be an autophagic stimulus, a defence mechanism of the body, against the cancer that is expanding and invading other tissues and organs. PMID- 27358156 TI - Isotonic saline in children with perennial allergic rhinitis. AB - Children with HDM allergy suffer from perennial allergic rhinitis (PAR). The present pilot study evaluated nasal lavage with isotonic saline (0.9%) in 25 children (mean age 8.9 years; 13 males) with HDM-dependent PAR, assessing: nasal symptoms severity and parental perception of rhinitis control, sleep, and school performance. Nasal symptoms, rated by total symptom score, parental perception of PER control, sleep quality, and school performance, measured by visual analogue scale, were significantly improved by nasal lavage (p < 0.001) after treatment. The effects tended to persist also during the follow-up. In conclusion, the present pilot study provides the first evidence that nasal lavage with isotonic saline relieved the nasal symptoms of children with PAR and improved the parental perception of the disease. PMID- 27358157 TI - Mandibular third molar displaced in the sublingual space: clinical management and medicolegal considerations. AB - This paper describes the management of a failed mandibular third molar extraction, resulting in tooth displacement in the sublingual space, the discussion of the diagnosis, surgery and medico-legal considerations. A 28-year old male patient underwent an unsuccessful attempt of the 4.8 tooth extraction. The clinician lost visual contact after luxation and the patient was not recalled for post-operative follow-up. After 24 hours, a severe trismus started. Ortopantomography and cone beam computer tomography revealed the displacement in the sublingual space. The tooth was removed under general anaesthesia with intraoral approach. The follow-up was uneventful and the paraesthetic area on the tongue did not enlarge after the retrieval. The displaced mandibular third molar is a rare but potentially serious complication of extraction. This event should be avoided with correct diagnosis and surgical technique. Cone beam computed tomography was useful to determine the three-dimensional position of the displaced tooth. PMID- 27358158 TI - Efficacy of pulsed low-intensity electric neuromuscular stimulation in reducing pain and disability in patients with myofascial syndrome. AB - Myofascial pain syndrome (MPS) is characterized by chronic pain in multiple myofascial trigger points and fascial constrictions. In recent years, the scientific literature has recognized the need to include the patient with MPS in a multidimensional rehabilitation project. At the moment, the most widely recognized therapeutic methods for the treatment of myofascial syndrome include the stretch and spray pressure massage. Microcurrent electric neuromuscular stimulation was proposed in pain management for its effects on normalizing bioelectricity of cells and for its sub-sensory application. In this study, we tested the efficacy of low-intensity pulsed electric neuromuscular stimulus (PENS) on pain in patients with MPS of cervical spine muscles. We carried out a prospective-analytic longitudinal study at an outpatient clinic during two weeks. Forty subjects (mean age 42+/-13 years) were divided into two groups: treatment (TrGr, n=20) and control group (CtrlGr, n=20). Visual-analog scale (VAS) values, concerning the spontaneous and movement-related pain in the cervical-dorsal region at baseline (T0) and at the end of the study (T1), showed a reduction from 7 to 3.81 (p < 0.001) in TrGr. In the CtrlGr, VAS was reduced from 8.2 to 7.2 (n.s.). Moreover, the pressure pain threshold at T0 was 2.1 vs 4.2 at T1 (p < 0.001) in TrG. In the CtrlGR we observed no significant changes. Modulated low intensity PENS is an innovative therapy permitting to act on the transmission of pain and on the restoration of tissue homeostasis. It seems to affect the transmission of pain through the stimulation of A-beta fibers. The above results show that low-intensity PENS can be considered as an effective treatment to reduce pain and disability in patients with MPS. PMID- 27358159 TI - Comparison between intrarticular injection of hyaluronic acid, oxygen ozone, and the combination of both in the treatment of knee osteoarthrosis. AB - This study aimed to compare short-term clinical outcomes between intra-articular injection of hyaluronic acid (HA), oxygen ozone (O2O3), and the combination of both, in patients affected by osteoarthrosis (OA) of the knee. Seventy patients (age 45-75 years) with knee OA were randomized to intra-articular injections of HA (n=23), or O2O3 (n=23) or combined (n=24) one per week for 5 consecutive weeks. KOOS questionnaire and visual analog scale (VAS), before treatment (pre) at the end (post), and at 2 months after treatment ended (follow-up) were used as outcome measures. Analysis showed a significant effect (P < 0.05) of the conditions (pre, post and follow-up) in all parameters of the KOOS score and a significant effect (P < 0.05) of groups (HA, O2O3 and combined) for pain, symptoms, activities of daily living and quality of life. The combined group scores were higher compared to the HA and O2O3 groups, especially at follow-up. The combination of O2O3 and HA treatment led to a significantly better outcome especially at 2-month follow-up compared to HA and O2O3 given separately to patients affected by OA of the knee. PMID- 27358160 TI - Rebuttal from Alexandros N. Vgontzas, Jordan Gaines, Silke Ryan and Walter T. McNicholas. PMID- 27358161 TI - Chemo- and Regioselective Direct Functional Group Installation through Catalytic Hydroxy Group Selective Conjugate Addition of Amino Alcohols to alpha,beta Unsaturated Sulfonyl Compounds. AB - A chemoselective functional group installation through catalytic hydroxy group selective conjugate addition of amino alcohols to a variety of functionalized alpha,beta-unsaturated sulfonyl derivatives was developed. Azide group installation for click chemistry and facile fluorescent labeling onto the less reactive hydroxy group demonstrated the synthetic utility of the present chemoselective catalysis. Moreover, chemo- and regioselective reaction of an unprotected amino diol was achieved for the first time. PMID- 27358162 TI - Effect of vitamin D supplementation on endothelial dysfunction in hemodialysis patients. AB - INTRODUCTION: Patients with chronic kidney disease (CKD) commonly experience 25 hydroxyvitamin D3 (25-OH-D3) deficiency, and these patients have a higher incidence of cardiovascular diseases (CVDs) due to endothelial dysfunction (ED). The aim of our study was to investigate the effect of 25-OH-D3 deficiency and its supplementation on ED in patients with CKD. METHODS: Twenty-nine uremic patients on dialysis and 20 healthy controls were evaluated for ED by high-resolution Doppler ultrasonography of the brachial artery. In addition, 25-OH-D3-deficient patients (25-OH-D3 < 30 nmol/L) with CKD and healthy controls were evaluated for ED before and after 8 weeks of oral vitamin D (cholecalciferol, 50,000 units) treatment. All subjects were evaluated for percent flow-mediated dilatation (%FMD), percent endothelium-independent nitroglycerin-induced vasodilatation (%NID), and bilateral carotid intima-media thickness (CIMT). FINDINGS: Patients on dialysis had lower %FMD and %NID 6.11 [2.27-12.74] and 10.96 [5.43-16.4], respectively, than controls 15.84 [8.19-22.49] and 21.74 [12.49-29.4], respectively (P < 0.05). Patients on dialysis had higher left and right CIMT (0.79 +/- 0.15 and 0.78 +/- 0.14, respectively) than controls (0.60 +/- 0.09 and 0.59 +/- 0.09, respectively; P < 0.05). In 25-OH-D3-deficient patients with CKD, after vitamin D treatment, %FMD was significantly increased in dialysis patients (10.25 [7.8-12.8]) compared to before supplementation (5.4 [2.77-6.15]; P < 0.001). DISCUSSION: These results indicated that dialysis patients had significantly lower blood 25-OH-D3 levels and higher CIMT than healthy subjects. In addition, vitamin D supplementation improved ED and increased %FMD in dialysis patients. Our findings suggest that vitamin D supplementation in dialysis patients might prevent CVD. PMID- 27358163 TI - Expression and regulation of the differentiation regulators ERBB Receptor Feedback Inhibitor 1 (ERRFI1) and Interferon-related Developmental Regulator 1 (IFRD1) during the periovulatory period in the rat ovary. AB - The current study investigated the regulation and the spatiotemporal expression pattern of Errfi1 and Ifrd1, genex encoding factors that regulate differentiation and cessation of cell division, in the rat ovary during the periovulatory period. Immature female rats (22-23 days old) were injected with pregnant-mare serum gonadotropin to stimulate folliculogenesis, followed by human chorionic gonadotropin (hCG) to induce ovulation. Ovaries, granulosa cells, theca interstitial cells, or cumulus oocyte complexes (COCs) were collected at various times after hCG administration (n = 3 per time point). Expression analysis revealed that Errfi1 and Ifrd1 were highly induced in the ovary, although their spatiotemporal expression differed: In situ hybridization analysis demonstrated that Errfi1 mRNA expression was initially induced in theca-interstitial cells at 4 and 8 hr after hCG, then transitioned to granulosa cells at 12 hr, and decreased in newly forming corpora lutea at 24 hr. Ifrd1 mRNA, on the other hand, was primarily induced in granulosa cells, and expression remained elevated in newly forming corpora lutea. Interestingly, Errfi1 and Ifrd1 were also expressed in the COC, suggesting a potential role in cumulus cell expansion or oocyte maturation. Inhibition of progesterone or prostaglandin synthesis reduced Errfi1 and Ifrd1 transcription, whereas inhibition of epidermal growth factor signaling inhibited only Errfi1 mRNA abundance. Down-regulation of both genes led to further suppression of progesterone. Our findings thus suggest that the stimulation of Errfi1 and Ifrd1 may be important for theca and granulosa cell differentiation and COC expansion. Mol. Reprod. Dev. 83: 714-723, 2016 (c) 2016 Wiley Periodicals, Inc. PMID- 27358164 TI - Nitrogen deposition may enhance soil carbon storage via change of soil respiration dynamic during a spring freeze-thaw cycle period. AB - As crucial terrestrial ecosystems, temperate forests play an important role in global soil carbon dioxide flux, and this process can be sensitive to atmospheric nitrogen deposition. It is often reported that the nitrogen addition induces a change in soil carbon dioxide emission in growing season. However, the important effects of interactions between nitrogen deposition and the freeze-thaw-cycle have never been investigated. Here we show nitrogen deposition delays spikes of soil respiration and weaken soil respiration. We found the nitrogen addition, time and nitrogen addition*time exerted the negative impact on the soil respiration of spring freeze-thaw periods due to delay of spikes and inhibition of soil respiration (p < 0.001). The values of soil respiration were decreased by 6% (low-nitrogen), 39% (medium-nitrogen) and 36% (high-nitrogen) compared with the control. And the decrease values of soil respiration under medium- and high nitrogen treatments during spring freeze-thaw-cycle period in temperate forest would be approximately equivalent to 1% of global annual C emissions. Therefore, we show interactions between nitrogen deposition and freeze-thaw-cycle in temperate forest ecosystems are important to predict global carbon emissions and sequestrations. We anticipate our finding to be a starting point for more sophisticated prediction of soil respirations in temperate forests ecosystems. PMID- 27358165 TI - Mindfulness-based cognitive therapy is effective as relapse prevention for patients with recurrent depression in Scandinavian primary health care. AB - This study examined the effectiveness of mindfulness-based cognitive therapy (MBCT) in primary care for patients with recurrent depression (major depressive disorder: MDD). According to the World Health Organization (WHO), MDD is now the leading cause of disease burden in middle- and high-income countries. Patients (N = 45) with three or more previous depressive episodes were recruited to participate in MBCT as a preventative intervention. Using a benchmarking approach, outcome data was compared with data from a recent efficacy study. The methodology is a rigorous approach to assessing effectiveness when evidence-based UK protocols are transferred into the existing Scandinavian service delivery. Additionally, a person-centred methodological approach was used to assess clinical significance on the Reliable Change Index (RCI). The analysis revealed comparable or larger effects from pre-test to post-test in reduced psychiatric symptoms, increased quality of life and level of mindfulness, and the effects were maintained over 14 months. Analysis of the relapse rate in the current study (16%) compared to the TAU in the efficacy study (68%) yielded an h value of 0.78, a moderate effect size. Only 13% dropped out of the treatment. According to the RCI findings, 65% to 67% of participants in the clinical group improved, no individual worsened, and women showed a significantly greater improvement of depression and anxiety than men. Therapeutic alliance and motivation had no impact on the outcome. The overall result suggests that MBCT can be implemented successfully in Scandinavian primary health care as a preventive intervention for patients with recurrent depression. PMID- 27358166 TI - Wheat CBL-interacting protein kinase 25 negatively regulates salt tolerance in transgenic wheat. AB - CBL-interacting protein kinases are involved in plant responses to abiotic stresses, including salt stress. However, the negative regulating mechanism of this gene family in response to salinity is less reported. In this study, we evaluated the role of TaCIPK25 in regulating salt response in wheat. Under conditions of high salinity, TaCIPK25 expression was markedly down-regulated in roots. Overexpression of TaCIPK25 resulted in hypersensitivity to Na(+) and superfluous accumulation of Na(+) in transgenic wheat lines. TaCIPK25 expression did not decline in transgenic wheat and remained at an even higher level than that in wild-type wheat controls under high-salinity treatment. Furthermore, transmembrane Na(+)/H(+) exchange was impaired in the root cells of transgenic wheat. These results suggested that TaCIPK25 negatively regulated salt response in wheat. Additionally, yeast-one-hybrid, beta-glucuronidase activity and DNA protein-interaction-enzyme-linked-immunosorbent assays showed that the transcription factor TaWRKY9 bound W-box in the TaCIPK25 promoter region. Quantitative real-time polymerase chain reaction assays showed concomitantly inverted expression patterns of TaCIPK25 and TaWRKY9 in wheat roots under salt treatment, ABA application and inhibition of endogenous ABA condition. Overall, based on our results, in a salt stress condition, the negative salt response in wheat involved TaCIPK25 with the expression regulated by TaWRKY9. PMID- 27358167 TI - Acitretin in erosive penile lichen planus. AB - Lichen planus (LP) is an incompletely understood T-cell mediated auto-immune dermatosis. When LP involves the genitalia it may present as painful, pruritic erosions that can be exquisitely tender, causing distress and genitourinary and sexual dysfunction. Management of erosive genital LP is often suboptimal. Despite higher order evidence demonstrating the efficacy of oral acitretin in the management of cutaneous and oral LP, it still features below other immunosuppressive and immunomodulatory therapies in many clinicians' therapeutic ladder. We present a case of severe erosive penile LP, successfully treated with oral acitretin after topical and oral corticosteroids failed to induce remission. PMID- 27358168 TI - Probing the minimal determinants of zinc binding with computational protein design. AB - Structure-based protein design tests our understanding of the minimal determinants of protein structure and function. Previous studies have demonstrated that placing zinc binding amino acids (His, Glu, Asp or Cys) near each other in a folded protein in an arrangement predicted to be tetrahedral is often sufficient to achieve binding to zinc. However, few designs have been characterized with high-resolution structures. Here, we use X-ray crystallography, binding studies and mutation analysis to evaluate three alternative strategies for designing zinc binding sites with the molecular modeling program Rosetta. While several of the designs were observed to bind zinc, crystal structures of two designs reveal binding configurations that differ from the design model. In both cases, the modeling did not accurately capture the presence or absence of second-shell hydrogen bonds critical in determining binding-site structure. Efforts to more explicitly design second-shell hydrogen bonds were largely unsuccessful as evidenced by mutation analysis and low expression of proteins engineered with extensive primary and secondary networks. Our results suggest that improved methods for designing interaction networks will be needed for creating metal binding sites with high accuracy. PMID- 27358169 TI - Symptoms and quality of life in patients with brain metastases receiving whole brain radiation therapy. AB - PURPOSE: Patients with multiple brain metastases may be treated with whole-brain radiation therapy (WBRT). For these patients, symptom palliation and improvement of quality of life (QOL) and performance status is of the upmost importance. The objective of the present study was to determine the symptom experience and overall QOL in patients with brain metastases before and after WBRT. METHODS: A total of 14 symptom scores and overall QOL were collected prospectively in 217 patients for up to 3 months. Wilcoxon signed rank test was applied to determine significant symptoms and QOL changes. Spearman's correlations were applied to determine the relationship between symptom scores and QOL. RESULTS: Appetite loss, weakness, and nausea significantly increased from baseline, while balance, headache, and anxiety significantly decreased from baseline. At baseline, all symptoms other than coordination were significantly correlated with QOL. At 1 month follow-up (FU), changes in concentration, weakness, coordination, and balance were significantly associated with QOL changes. At 2-month FU, changes in pain, insomnia, concentration, balance, and depression were significantly associated with QOL changes. At 3-month FU, only change in nausea was significantly associated with QOL changes. CONCLUSIONS: Following WBRT, certain symptoms may influence overall QOL to a greater extent than others, which may fluctuate with time. PMID- 27358170 TI - Caregivers' perspectives on oral health problems of end-of-life cancer patients. AB - PURPOSE: The purpose of this study was to determine caregivers' perspectives on oral health problems in cancer patients at the end of life and explore factors that contribute to those perspectives. METHODS: A cross-sectional, observational clinical study design was used. We recruited dyads of lay caregivers and patients with advanced cancer who were receiving hospice or palliative care in their homes. Caregivers [N = 104, mean age = 55.4 +/- 15.0 years (18-100); n = 50 (48 %) African-American; and n = 80 (77 %) female] completed the proxy version of the Oral Problems Scale to provide their perspectives regarding their care recipients' xerostomia, orofacial pain, and taste change in the past week. RESULTS: More than half of the caregivers reported that care recipients' oral hygiene was a very important responsibility for caregivers, and over 80 % reported that it was very important to evaluate their care recipients' oral problems. However, caregivers reported that they asked their care recipients about oral problems infrequently. There were statistically significant correlations between caregivers' and care recipients' ratings on xerostomia, orofacial pain, taste change, and functional/social impact. Caregivers' age and well-being predicted their awareness of care recipients' oral health problems. CONCLUSIONS: Future research efforts should focus on understanding the challenges that prevented caregivers from translating their awareness of the importance of care recipients' oral health to frequent evaluation and provision of oral care. PMID- 27358171 TI - New Developments in Platelet Cyclic Nucleotide Signalling: Therapeutic Implications. AB - Altered platelet physiology may contribute to the emergence of thrombosis in patients with many forms of cardiovascular disease. Excess platelet activation may reflect increased stimulation of pro-aggregatory pathways. There is, however, increasing evidence that excessive platelet response, due to impaired efficacy of anti-aggregatory autacoids such as nitric oxide (NO) and prostacyclin (PGI2), may be just as important. For example, diminished platelet response to NO has been documented in acute and chronic myocardial ischaemia, heart failure, aortic valve disease and in the presence of hyperglycaemia. This "NO resistance" has been shown to reflect both the scavenging of NO by reactive oxygen species and dysfunction of its intracellular "receptor", soluble guanylate cyclase. Importantly, these abnormalities of NO signalling are potentially reversible through judicious application of pharmacotherapy. The analogous condition of impaired PGI2/adenylate cyclase (AC) signalling has received comparatively less attention to date. We have shown that platelet response to prostaglandin E1 (PGE1) is frequently impaired in patients with symptomatic myocardial ischaemia. Because the effects of ADP receptor antagonists such as clopidogrel and ticagrelor at the level of the P2Y12 receptor are coupled with changes in activity of AC, impaired response to PGE1 might imply both increased thrombotic risk and a reduced efficacy of anti-aggregatory drugs. Accordingly, patient response to treatment with clopidogrel is determined not only by variability of clopidogrel bio-activation, but also extensively by the integrity of platelet AC signalling. We here review these recent developments and their emerging therapeutic implications for thrombotic disorders. PMID- 27358172 TI - Treatment of Angina Pectoris Associated with Coronary Microvascular Dysfunction. AB - Treatment of angina pectoris associated with coronary microvascular dysfunction is challenging as the underlying mechanisms are often diverse and overlapping. Patients with type 1 coronary microvascular dysfunction (i.e. absence of epicardial coronary artery disease and myocardial disease) should receive strict control of their cardiovascular risk factors and thus receive statins and ACE inhibitors in most cases. Antianginal medication consists of beta-blockers and/or calcium channel blockers. Second line drugs are ranolazine and nicorandil with limited evidence. Despite individually titrated combinations of these drugs up to 30 % of patients have refractory angina. Rho-kinase inhibitors and endothelin receptor antagonists represent potential drugs that may prove useful in these patients in the future. PMID- 27358173 TI - Rosuvastatin for Reduction of Myocardial Damage during Coronary Angioplasty - the Remedy Trial. AB - BACKGROUND: Periprocedural myocardial infarction (MI) is a frequent complication of percutaneous coronary intervention (PCI). Statins might reduce its incidence. The aims of the present study are to assess whether such benefit is a class effect or whether differences exist between various lipid-lowering strategies and whether cardioprotection is exerted by increasing circulating endothelial progenitor cells (EPCs). METHODS: The REMEDY study will enroll a total of 1080 patients submitted to elective PCI. Eligible patients will be randomized into 4 groups: 1) placebo; 2) atorvastatin (80 mg + 40 mg before PCI); 3) rosuvastatin (40 mg twice before PCI); and 4) rosuvastatin (5 mg) and ezetimibe (10 mg) twice before PCI. Peri-procedural MI is defined as an elevation of markers of cardiac injury (either CK-MB or troponin I or T) values >5x the upper reference limit estimated at the 99th percentile of the normal distribution, or a rise >20 % in case of baseline values already elevated. EPCs will be assessed before, at 24 h and - in a subset of diabetic patients - at 3 months after PCI (EPC-substudies). The primary endpoint of the main REMEDY study is the rate of peri-procedural MI in each of the 4 treatment arms. Secondary endpoints are the combined occurrence of 1-month major adverse events (MACE, including death, MI, or the need for unplanned revascularization); and any post-procedural increase in serum creatinine. Endpoints of the EPC-substudies are the impact of tested regimens on 1) early (24-h) and 3-month EPC levels and functional activity; 2) stent strut re endothelialization and neointimal hyperplasia; 3) 1-year MACE. REMEDY will add important information on the cardioprotective effects of statins after PCI. PMID- 27358175 TI - Cytomegalovirus Infection of Seminal Vesicles. PMID- 27358174 TI - Bile acids and nonalcoholic fatty liver disease: Molecular insights and therapeutic perspectives. AB - Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide and an important risk factor for both hepatic and cardiometabolic mortality. The rapidly increasing prevalence of this disease and of its aggressive form nonalcoholic steatohepatitis (NASH) will require novel therapeutic approaches to prevent disease progression to advanced fibrosis or cirrhosis and cancer. In recent years, bile acids have emerged as relevant signaling molecules that act at both hepatic and extrahepatic tissues to regulate lipid and carbohydrate metabolic pathways as well as energy homeostasis. Activation or modulation of bile acid receptors, such as the farnesoid X receptor and TGR5, and transporters, such as the ileal apical sodium-dependent bile acid transporter, appear to affect both insulin sensitivity and NAFLD/NASH pathogenesis at multiple levels, and these approaches hold promise as novel therapies. In the present review, we summarize current available data on the relationships of bile acids to NAFLD and the potential for therapeutically targeting bile-acid-related pathways to address this growing world-wide disease. (Hepatology 2017;65:350-362). PMID- 27358176 TI - Intraventricular Hemorrhage: the Role of Blood Components in Secondary Injury and Hydrocephalus. PMID- 27358177 TI - Predictors of bone mineral density testing among older women on Medicare. AB - : Although dual-energy X-ray absorptiometry (DXA) is recommended for all women >=65 and is covered by Medicare, 40 % of women on Medicare report never having had a DXA. In a longitudinal cohort of 3492 women followed for two decades, we identified several risk factors that should be targeted to improve DXA testing rates. INTRODUCTION: DXA is used to measure bone mineral density, screen for osteoporosis, and assess fracture risk. DXA is recommended for all women >=65 years old. Although Medicare covers DXA every 24 months for women, about 40 % report never having had a DXA test, and little is known from prospective cohort studies about which subgroups of women have low use rates and should be targeted for interventions. Our objective was to identify predictors of DXA use in a nationally representative cohort of women on Medicare. METHODS: We used baseline and biennial follow-up survey data (1993-2012) for 3492 women >=70 years old from the nationally representative closed cohort known as the Survey on Assets and Health Dynamics among the Oldest Old (AHEAD). The survey data for these women were then linked to their Medicare claims (1991-2012), yielding 17,345 person years of observation. DXA tests were identified from the Medicare claims, and Cox proportional hazard regression models were used with both fixed and time dependent predictors from the survey interviews including demographic characteristics, socioeconomic factors, health status, health habits, and the living environment. RESULTS: DXA use was positively associated with being Hispanic American, better cognition, higher income, having arthritis, using other preventative services, and living in Florida or other southern states. DXA use was negatively associated with age, being African-American, being overweight or obese, having mobility limitations, and smoking. CONCLUSIONS: Interventions to increase DXA use should target the characteristics that were observed here to be negatively associated with such screening. PMID- 27358178 TI - Incidence and clinical background of hepatitis B virus reactivation in multiple myeloma in novel agents' era. AB - There are some reports regarding hepatitis B virus (HBV) reactivation in patients with myeloma who are HBV carriers or who have had a resolved HBV infection, and there is no standard prophylaxis strategy for these patients. We performed a retrospective multicenter study to determine the incidence and characteristics of HBV reactivation in patients with multiple myeloma. We identified 641 patients with multiple myeloma who had been treated using novel agents and/or autologous stem cell transplantation with high-dose chemotherapy between January 2006 and June 2014 at nine Japanese hospitals. The patients' characteristics, laboratory data, and clinical courses were retrieved and statistically analyzed. During a median follow-up of 101 weeks, one of eight (12.5 %) HBV carriers developed hepatitis and 9 of 99 (9.1 %) patients with resolved HBV infection experienced HBV reactivation; the cumulative incidences of HBV reactivation at 2 years (104 weeks) and 5 years (260 weeks) were 8 and 14 %, respectively. The nine cases of reactivation after resolved HBV infection had received entecavir as preemptive therapy or were carefully observed by monitoring their HBV DNA levels, and none of these cases developed hepatitis. Among patients with multiple myeloma, HBV reactivation was not rare. Therefore, long-term monitoring of HBV DNA levels is needed to prevent hepatitis that is related to HBV reactivation in these patients. PMID- 27358179 TI - Mutations in MYT1, encoding the myelin transcription factor 1, are a rare cause of OAVS. AB - BACKGROUND: Oculo-auriculo-vertebral spectrum (OAVS) is a developmental disorder involving first and second branchial arches derivatives, mainly characterised by asymmetric ear anomalies, hemifacial microsomia, ocular defects and vertebral malformations. Although numerous chromosomal abnormalities have been associated with OAVS, no causative gene has been identified so far. OBJECTIVES: We aimed to identify the first causative gene for OAVS. METHODS: As sporadic cases are mostly described in Goldenhar syndrome, we have performed whole exome sequencing (WES) on selected affected individuals and their unaffected parents, looking for de novo mutations. Candidate gene was tested through transient knockdown experiment in zebrafish using a morpholino-based approach. A functional test was developed in cell culture in order to assess deleterious consequences of mutations. RESULTS: By WES, we identified a heterozygous nonsense mutation in one patient in the myelin transcription factor 1 (MYT1) gene. Further, we detected one heterozygous missense mutation in another patient among a cohort of 169 patients with OAVS. This gene encodes the MYT1. Functional studies by transient knockdown of myt1a, homologue of MYT1 in zebrafish, led to specific craniofacial cartilage alterations. Treatment with all-trans retinoic acid (RA), a known teratogenic agent causing OAVS, led to an upregulation of cellular endogenous MYT1 expression. Additionally, cellular wild-type MYT1 overexpression induced a downregulation of RA receptor beta (RARB), whereas mutated MYT1 did not. CONCLUSION: We report MYT1 as the first gene implicated in OAVS, within the RA signalling pathway. PMID- 27358182 TI - Importance of Social Relationships in Patients with Chronic Respiratory Diseases. AB - The literature lacks reports on the role of the social relationships domain (SRD) of quality of life (QoL) in shaping care for patients with chronic respiratory diseases in primary care. In this study we examined a group of 582 patients with chronic respiratory diseases and chronic non-respiratory diseases recruited from 199 primary care centers. In the patients with chronic respiratory diseases, higher SRD correlated with more frequent patient visits due to medical issue, fewer district nurse interventions over the past 12 months, less frequent hospitalizations over the past 3 years, and fewer chronic diseases. In these patients, a high SRD was most effectively created by high QoL in the Psychological, Environmental, and Physical domains, and the satisfaction with QoL. Programs for preventing a decline in SRD should include patients with low scores in the Psychological, Environmental, and Physical domains, those who show no improvement in mental or somatic well-being in the past 12 months, those with a low level of positive mental attitudes, unhealthy eating habits, and with low levels of met needs. Such programs should include older widows and widowers without permanent relationships, with only primary education, living far from a primary care center, and those whose visits were not due to a medical issue. PMID- 27358181 TI - Adiponectin and Mortality in Smokers and Non-Smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study. AB - Cardiovascular diseases (CVD) are an important cause of morbidity and mortality worldwide. A decreased concentration of adiponectin has been reported in smokers. The aim of this study was to analyze the effect of cigarette smoking on the concentration of adiponectin and potassium in active smokers (AS) and life-time non-smokers (NS) of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study, and the use of these two markers for risk prediction. Smoking status was assessed by a questionnaire and measurement of plasma cotinine concentration. The serum concentration of adiponectin was measured by ELISA. Adiponectin was binned into tertiles separately for AS and NS and the Cox regression was used to assess the effect on mortality. There were 777 AS and 1178 NS among the LURIC patients. Within 10 years (median) of follow-up 221 AS and 302 NS died. In unadjusted analyses, AS had lower concentrations of adiponectin. However, after adjustment for age and gender there was no significant difference in adiponectin concentration between AS and NS. In the Cox regression model adjusted for age and gender, adiponectin was significantly associated with mortality in AS, but not in NS, with hazard ratio (95 % CI) of 1.60 (1.14-2.24) comparing the third with first tertile. In a model further adjusted for the risk factors, such as diabetes mellitus, hypertension, coronary artery disease, body mass index, LDL-cholesterol and HDL-cholesterol, adiponectin was significantly associated with mortality with hazard ratio of 1.83 (1.28-2.62) and 1.56 (1.15-2.11) for AS and NS, respectively. We conclude that increased adiponectin is a strong and independent predictor of mortality in both AS and NS. The determination of adiponectin concentration could be used to identify individuals at increased mortality risk. PMID- 27358183 TI - Active Site Characterization of Proteases Sequences from Different Species of Aspergillus. AB - A total of 129 proteases sequences comprising 43 serine proteases, 36 aspartic proteases, 24 cysteine protease, 21 metalloproteases, and 05 neutral proteases from different Aspergillus species were analyzed for the catalytically active site residues using MEROPS database and various bioinformatics tools. Different proteases have predominance of variable active site residues. In case of 24 cysteine proteases of Aspergilli, the predominant active site residues observed were Gln193, Cys199, His364, Asn384 while for 43 serine proteases, the active site residues namely Asp164, His193, Asn284, Ser349 and Asp325, His357, Asn454, Ser519 were frequently observed. The analysis of 21 metalloproteases of Aspergilli revealed Glu298 and Glu388, Tyr476 as predominant active site residues. In general, Aspergilli species-specific active site residues were observed for different types of protease sequences analyzed. The phylogenetic analysis of these 129 proteases sequences revealed 14 different clans representing different types of proteases with diverse active site residues. PMID- 27358180 TI - De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy. AB - BACKGROUND: Mutations in the KIAA2022 gene have been reported in male patients with X-linked intellectual disability, and related female carriers were unaffected. Here, we report 14 female patients who carry a heterozygous de novo KIAA2022 mutation and share a phenotype characterised by intellectual disability and epilepsy. METHODS: Reported females were selected for genetic testing because of substantial developmental problems and/or epilepsy. X-inactivation and expression studies were performed when possible. RESULTS: All mutations were predicted to result in a frameshift or premature stop. 12 out of 14 patients had intractable epilepsy with myoclonic and/or absence seizures, and generalised in 11. Thirteen patients had mild to severe intellectual disability. This female phenotype partially overlaps with the reported male phenotype which consists of more severe intellectual disability, microcephaly, growth retardation, facial dysmorphisms and, less frequently, epilepsy. One female patient showed completely skewed X-inactivation, complete absence of RNA expression in blood and a phenotype similar to male patients. In the six other tested patients, X inactivation was random, confirmed by a non-significant twofold to threefold decrease of RNA expression in blood, consistent with the expected mosaicism between cells expressing mutant or normal KIAA2022 alleles. CONCLUSIONS: Heterozygous loss of KIAA2022 expression is a cause of intellectual disability in females. Compared with its hemizygous male counterpart, the heterozygous female disease has less severe intellectual disability, but is more often associated with a severe and intractable myoclonic epilepsy. PMID- 27358184 TI - Characterization of endometriosis-associated immune cell infiltrates (EMaICI). AB - OBJECTIVE: To identify and characterize endometriosis-associated immune cell infiltrates (EMaICI). Furthermore, to define occurrence and size of EMaICI in various types of endometriosis. METHODS: Immune cells were characterized in samples of 60 premenopausal women with histological proven endometriosis. Therefore, immunohistochemical staining with monoclonal antibodies for CD3, CD4, CD8, CD45RO, CD25, CD56, CD68, and CD20 on sections of paraffin-embedded endometriotic tissue was performed. RESULTS: EMaICI were observed in all the types of endometriosis, and characterized as T lymphocytes (CD3+), helper T lymphocytes (CD4+), cytotoxic T lymphocytes (CD8+), antigen-experienced T lymphocytes"memory cells" (CD45RO+), macrophages (CD68+), and B lymphocytes (CD20+). The maximum frequency of EMaICI and their distribution per endometriotic lesion (EML) was observed in peritoneal endometriosis (pEM) and in ovarian endometriosis (Ov. EM). In myometrium from adenomyosis (M/AM), EMaICI occurrence was lower and smaller in size in comparison with EMaICI seen in other forms of endometriosis. EMaICI were negative for regulatory T cells (CD25+ high, FoxP3+) and natural killer cells (NK cells, CD56+). CONCLUSION: Numerous and brisk EMaICI comprising several types of immune cells in all endometriosis forms suggest acute immunological reactions within the microenvironment of endometriosis lesions. PMID- 27358185 TI - Early Life Health, Trauma and Social Determinants of Lifetime Abstention from Alcohol. AB - AIMS: Factors influencing lifetime abstention from alcohol may be relevant to the validity of analyses of alcohol's impact on health outcomes. We evaluate relationships between early life experiences, social factors, and demographic characteristics on lifetime abstainer status in models disaggregating by gender and, among women, race/ethnicity. METHODS: Analyses use the landline sample (N = 5382) of the 2010 U.S. National Alcohol Survey. Surveyed participants who reported never drinking alcohol were defined as lifetime abstainers. Additional variables assessed included demographics, dispositions to risk taking and impulsivity, and indicators of early life stress like economic difficulty, childhood trauma and early onset of health conditions. Logistic regression models predicting lifetime abstention were estimated. RESULTS: Lifetime abstainers are more likely to be women and, among women, to be non-White and Latina. Those reporting that their religion discouraged drinking and that religion was very important to them were more likely to be lifetime abstainers. Higher education levels were associated with reduced rates of lifetime abstention among women. Also among women, family problem drinking was associated with lower rates of lifetime abstention. However, childhood economic difficulty significantly predicted lower abstention only for White women, and childhood sexual abuse was significantly related to lower lifetime abstention only for Black women. CONCLUSIONS: Understanding the characteristics and determinants of individuals who never drink alcohol is relevant to any analysis of alcohol-related health outcomes. Results point to specific factors related to lifetime abstention with potential to bias such analyses if not included as control measures. SHORT SUMMARY: Analyses evaluating relationships between early life experiences, social factors, and demographics with lifetime abstainer status identified characteristics associated with both poor health and with better health. These included lower risk taking and impulsivity scores and lower rates of family problem drinking, childhood economic difficulties and childhood sexual abuse. PMID- 27358186 TI - Women and Men Admitted for Alcohol Intoxication at an Emergency Department: Alcohol Use Disorders, Substance Use and Health and Social Status 7 Years Later. AB - AIMS: To assess the prevalence of alcohol use disorder (AUD), substance use, mental health and social status 7 years following an Emergency Department (ED) admission for alcohol intoxication. To assess gender differences in these prevalences. METHODS: Cohort of 631 patients aged 18-30 years admitted for alcohol intoxication in 2006-2007 at a tertiary referral hospital in Switzerland, contacted for an interview in 2014. Assessment consisted of demography, Alcohol Use Disorders Identification Test-Consumption, Mini International Neuropsychiatric Interview for AUD, Patient Health Questionnaire (depression, anxiety) and lifetime/past year use of tobacco/illegal drugs. Gender differences were assessed with Chi-square tests, t-tests and Wilcoxon tests. RESULTS: In 2014, 318/631 (50.4%) completed the interview. Study completers were not different from non-completers on baseline characteristics (all P > 0.2). Of study completers, 36.8% were unemployed, 56.9% reported hazardous alcohol use, 15.1% alcohol dependence, 13.2% harmful use, 18.6% depression, 15.4% anxiety disorder. Prevalence of any use (lifetime/past year) was 93.4%/80.2% for tobacco, 86.6%/53.1% for cannabis, 54.7%/22.6% for cocaine, 25.6%/13.5% for sedatives, 40.9%/11.0% for stimulants, 21.7%/7.2% for opioids. Men reported significantly more binge drinking, AUD, cannabis use (past year) and more lifetime cannabis, cocaine and stimulants use (all P < 0.05). There was no gender difference in the prevalence of hazardous alcohol use and tobacco use. The prevalence of psychiatric disorders was significantly higher in women (P < 0.05). CONCLUSIONS: Seven years after being admitted for alcohol intoxication, young patients are likely to present substance misuse, mental health disorders and social problems, suggesting that they should be offered secondary prevention measures while in the ED. SHORT SUMMARY: We studied a cohort of patients aged 18-30 and admitted for alcohol intoxication in 2006-2007 at a tertiary hospital. Participants were interviewed in 2014. Seven years after an admission for alcohol intoxication, patients are likely to present AUDs, substance misuse, mental health disorders and social problems. PMID- 27358187 TI - Cutaneous Squamous Cell Carcinoma: A Review of High-Risk and Metastatic Disease. AB - Non-melanoma skin cancer represents one-third of all malignancies and its incidence is expected to rise until the year 2040. Cutaneous squamous cell carcinoma (cSCC) represents 20 % of all non-melanoma skin cancer and is a deadly threat owing to its ability to metastasize to any organ in the body. Therefore, a better understanding of cSCC is essential to strengthen preventative measures and curable treatment options. Currently, research demonstrates that cSCC is diagnosed at a rate of 15-35 per 100,000 people and is expected to increase 2-4 % per year. With respect to metastatic cSCC, this disease is more common in men; people over the age of 75 years; and inhabitants of the south and mid-west USA. In 2010, the American Joint Committee on Cancer updated the Cancer Staging Manual's primary tumor designation to now include high-risk factors; however, factors such as immunosuppression and tumor recurrence were not included. Other staging systems such as Brigham and Women's Hospital have allowed for increased stratification of cSCC. High-risk cSCC is defined as a cSCC that is staged as N0, extends beyond basement membrane, and has high-risk features associated with sub clinical metastasis. High-risk features are depth of invasion (>2 mm), poor histological differentiation, high-risk anatomic location (face, ear, pre/post auricular, genitalia, hands, and feet), perineural involvement, recurrence, multiple cSCC tumors, and immunosuppression. Epidermal growth factor receptor and nuclear active IkappaB kinase (IKK) expression are also predictive of metastatic capabilities. Clinically, the initial lesions of a cSCC tumor can present as a painless plaque-like or verrucous tumor that can ultimately progress to being large, necrotic, and infected. Tumors can also present with paresthesias or lymphadenopathy depending on the location involved. With respect to prognosis, metastatic cSCC is lethal, with several large studies demonstrating a mortality rate of >70 %. Therefore, treatment of metastatic cSCC is difficult and depends on the location involved and extent of metastasis. Treatment options include surgery, radiation therapy, chemotherapy, and any combination of the above. Surgery alone can be used for metastatic cSCC treatment, but is not as effective as surgery in conjunction with radiation therapy. Radiation therapy has some success as a monotherapy in low-risk or cosmetically sensitive areas such as the external ear, eyelid or nose. According to the 2013 National Comprehensive Cancer Network Guidelines, cisplatin as a single agent or combined with 5-fluorouracil hold the strongest support for the treatment of metastatic cSCC; however, the supporting evidence is inconsistent and a curative chemotherapeutic approach is still lacking. Epidermal growth factor receptor inhibitors are a newer class of agents being used in metastatic cSCC and hold some promise as a therapy for this disease. Other areas of interest in finding curative treatments for metastatic cSCC include p53, hypermethylation of specific genes, chromatin remodeling genes, and the RAS/RTK/PI3K pathway. This review addresses the epidemiology, staging, risk factors, clinical presentation, management, and new trends in the treatment of high-risk and metastatic cSCC. PMID- 27358188 TI - Risk factors for heparin-induced thrombocytopenia: Focus on Fcgamma receptors. AB - Fcgamma receptors have critical roles in the pathophysiology of heparin-induced thrombocytopenia (HIT), a severe immune-mediated complication of heparin treatment. Activation of platelets, monocytes and neutrophils by platelet activating anti-PF4/heparin IgG antibodies results in thrombocytopenia, hypercoagulability and thrombosis in susceptible patients, effects that depend on FcgammaRIIA. In addition, FcgammaRIIIA receptors probably contribute to clearance of platelets sensitised by HIT immune complexes. FcgammaRI has also been reported to be involved in monocyte activation by HIT IgG antibodies and synthesis of tissue factor. This review focuses on the role of these FcgammaRs in HIT pathophysiology, including the potential influence of several gene variations associated with variable risk of HIT and related thrombosis. In particular, the 276P and 326Q alleles of CD148, a protein tyrosine phosphatase that regulates FcgammaRIIA signalling, are associated with a lower risk of HIT, and platelets from healthy donors expressing these alleles are hyporesponsive to anti-PF4/H antibodies. It was also recently demonstrated that the risk of thrombosis is higher in HIT patients expressing the R isoform of the FcgammaRIIA H131R polymorphism, with HIT antibodies shown to activate RR platelets more efficiently, mainly explained by an inhibitory effect of normal IgG2, which bound to the FcgammaRIIA 131H isoform more efficiently. Environmental risk factors probably interact with these gene polymorphisms affecting FcgammaRs, thereby increasing thrombosis risk in HIT. PMID- 27358189 TI - Iodine Content in Milk Alternatives. AB - BACKGROUND: Iodine is necessary for the production of thyroid hormones and is acquired through the diet. Cow's milk is a primary source of iodine in the U.S. diet. The objective of this study was to measure the iodine content in a variety of milk alternatives to determine whether milk alternatives contain iodine levels comparable to that of cow's milk. METHODS: Iodine levels from 30 different brands of milk alternatives from 16 different companies were measured by the spectrophotometric method of the Sandell-Kolthoff reaction. RESULTS: The 30 brands of milk alternatives contained an average of 3.1 +/- 2.5 MUg/250 mL (~8 oz. or one cup, serving size) of iodine or 12.3 +/- 10.1 MUg/L (~24 oz. or four cups, daily recommended serving for adequate calcium intake) of iodine. CONCLUSIONS: These results indicate that milk alternatives contain far less iodine than cow's milk. Individuals with restricted dairy product consumption are at risk for inadequate dietary iodine intake. PMID- 27358190 TI - Has Aspergillus PCR Come to the Age of Maturity? PMID- 27358191 TI - Small Glutamine-Rich Tetratricopeptide Repeat-Containing Protein Alpha (SGTA) Ablation Limits Offspring Viability and Growth in Mice. AB - Small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA) has been implicated as a co-chaperone and regulator of androgen and growth hormone receptor (AR, GHR) signalling. We investigated the functional consequences of partial and full Sgta ablation in vivo using Cre-lox Sgta-null mice. Sgta(+/-) breeders generated viable Sgta(-/-) offspring, but at less than Mendelian expectancy. Sgta(-/-) breeders were subfertile with small litters and higher neonatal death (P < 0.02). Body size was significantly and proportionately smaller in male and female Sgta(-/-) (vs WT, Sgta(+/-) P < 0.001) from d19. Serum IGF-1 levels were genotype- and sex-dependent. Food intake, muscle and bone mass and adiposity were unchanged in Sgta(-/-). Vital and sex organs had normal relative weight, morphology and histology, although certain androgen-sensitive measures such as penis and preputial size, and testis descent, were greater in Sgta(-/-). Expression of AR and its targets remained largely unchanged, although AR localisation was genotype- and tissue-dependent. Generally expression of other TPR-containing proteins was unchanged. In conclusion, this thorough investigation of SGTA-null mutation reports a mild phenotype of reduced body size. The model's full potential likely will be realised by genetic crosses with other models to interrogate the role of SGTA in the many diseases in which it has been implicated. PMID- 27358192 TI - Mutation of DNA Polymerase beta R137Q Results in Retarded Embryo Development Due to Impaired DNA Base Excision Repair in Mice. AB - DNA polymerase beta (Pol beta), a key enzyme in the DNA base excision repair (BER) pathway, is pivotal in maintaining the integrity and stability of genomes. One Pol beta mutation that has been identified in tumors, R137Q (arginine to glutamine substitution), has been shown to lower polymerase activity, and impair its DNA repair capacity. However, the exact functional deficiency associated with this polymorphism in living organisms is still unknown. Here, we constructed Pol beta R137Q knock-in mice, and found that homozygous knock-in mouse embryos were typically small in size and had a high mortality rate (21%). These embryonic abnormalities were caused by slow cell proliferation and increased apoptosis. In R137Q knock-in mouse embryos, the BER efficiency was severely impaired, which subsequently resulted in double-strand breaks (DSBs) and chromosomal aberrations. Furthermore, R137Q mouse embryo fibroblasts (MEFs) were more sensitive to DNA damaging reagents, such as methyl methanesulfonate (MMS) and H2O2. They displayed a higher percentage of DSBs, and were more likely to undergo apoptosis. Our results indicate that R137 is a key amino acid site that is essential for proper Pol beta functioning in maintaining genomic stability and embryo development. PMID- 27358193 TI - Midpoint attractors and species richness: Modelling the interaction between environmental drivers and geometric constraints. AB - We introduce a novel framework for conceptualising, quantifying and unifying discordant patterns of species richness along geographical gradients. While not itself explicitly mechanistic, this approach offers a path towards understanding mechanisms. In this study, we focused on the diverse patterns of species richness on mountainsides. We conjectured that elevational range midpoints of species may be drawn towards a single midpoint attractor - a unimodal gradient of environmental favourability. The midpoint attractor interacts with geometric constraints imposed by sea level and the mountaintop to produce taxon-specific patterns of species richness. We developed a Bayesian simulation model to estimate the location and strength of the midpoint attractor from species occurrence data sampled along mountainsides. We also constructed midpoint predictor models to test whether environmental variables could directly account for the observed patterns of species range midpoints. We challenged these models with 16 elevational data sets, comprising 4500 species of insects, vertebrates and plants. The midpoint predictor models generally failed to predict the pattern of species midpoints. In contrast, the midpoint attractor model closely reproduced empirical spatial patterns of species richness and range midpoints. Gradients of environmental favourability, subject to geometric constraints, may parsimoniously account for elevational and other patterns of species richness. PMID- 27358194 TI - Impact of Coronary Artery Disease Burden on 12-Month Mortality of Patients After Transcatheter Aortic Valve Implantation. AB - OBJECTIVES: The aim of the study was to compare 12-month mortality rate of patients with and without complete coronary revascularization before transcatheter aortic valve implantation (TAVI). BACKGROUND: There are limited data on the impact of coronary artery disease burden in patients with severe aortic stenosis undergoing TAVI. METHODS: One hundred and one consecutive patients undergoing TAVI were enrolled. Of them 16 (15.8%) had an incomplete coronary revascularization. The primary endpoint was 12-month all-cause mortality. RESULTS: Twelve-month all-cause mortality was higher in patients with incomplete coronary revascularization than in patients with complete coronary revascularization or without significant lesions (75.0% vs 7.1%; P < 0.001). Importantly, incomplete coronary revascularization was an independent predictor of higher mortality rate after 12 months (hazard ratio (HR) for incomplete coronary revascularization 10.86, 95% CI 3.72-31.73; P < 0.001; HR for a history of stroke/TIA 3.93, 95% confidence interval (CI) 1.39-11.07; P < 0.001; HR for blood transfusion 2.84 95% CI (1.06-7.63); P = 0.039). In 9 of 16 (56.3%) patients, incomplete revascularization was related to the presence of chronic total occlusions (CTO). Patients with CTO had an increased mortality rate after 12 months (55.6% vs 14.1%; P = 0.008) as compared to patients without the CTO. CONCLUSIONS: Incomplete coronary revascularization and a history of stroke or TIA may be independent predictors of all-cause mortality in patients undergoing TAVI. However, further studies are recommended to confirm the results, especially in terms of the impact of CTO presence on long-term mortality after TAVI. PMID- 27358195 TI - Self-Templating and In Situ Assembly of a Cubic Cluster-of-Clusters Architecture Based on a {Mo24 Fe12 } Inorganic Macrocycle. AB - Engineering self-templating inorganic architectures is critical for the development of bottom-up approaches to nanoscience, but systems with a hierarchy of templates are elusive. Herein we describe that the cluster-anion-templated (CAT) assembly of a {CAT}?{Mo24 Fe12 } macrocycle forms a giant ca. 220 nm(3) unit cell containing 16 macrocycles clustered into eight face-shared tetrahedral cluster-of-clusters assemblies. We show that {CAT}?{Mo24 Fe12 } with different CATs gives the compounds 1-4 for CAT=Anderson {FeMo6 } (1), Keggin {PMo12 } (2), Dawson {P2 W18 } (3), and {Mo12 O36 (HPO3 )2 } (4) polyoxometalates. "Template free" assembly can be achieved, whereby the macrocycle components can also form a template in situ allowing template to macrocycle to superstructure formation and the ability to exchange the templates. Furthermore, the transformation of template clusters within the inorganic macrocycle {Mo24 Fe12 } allows the self generation of an uncapped {Mo12 O36 (HPO3 )2 } in compound 4. PMID- 27358196 TI - Application of Dempster-Shafer theory, spatial analysis and remote sensing for groundwater potentiality and nitrate pollution analysis in the semi-arid region of Khuzestan, Iran. AB - Effective management and sustainable development of groundwater resources of arid and semi-arid environments require monitoring of groundwater quality and quantity. The aim of this paper is to develop a reasonable methodological framework for producing the suitability map for drinking water through the geographic information system, remote sensing and field surveys of the Andimeshk Dezful, Khozestan province, Iran as a semi-arid region. This study investigated the delineation of groundwater potential zone based on Dempster-Shafer (DS) theory of evidence and evaluate its applicability for groundwater potentiality mapping. The study also analyzed the spatial distribution of groundwater nitrate concentration; and produced the suitability map for drinking water. The study has been carried out with the following steps: i) creation of maps of groundwater conditioning factors; ii) assessment of groundwater occurrence characteristics; iii) creation of groundwater potentiality map (GPM) and model validation; iv) collection and chemical analysis of water samples; v) assessment of groundwater nitrate pollution; and vi) creation of groundwater potentiality and quality map. The performance of the DS was also evaluated using the receiver operating characteristic (ROC) curve method and pumping test data to ensure its generalization ability, which eventually, the GPM showed 87.76% accuracy. The detailed analysis of groundwater potentiality and quality revealed that the 'non acceptable' areas covers an area of about 1479km(2) (60%). The study will provide significant information for groundwater management and exploitation in areas where groundwater is a major source of water and its exploration is critical to support drinking water need. PMID- 27358197 TI - Sub-lethal cadmium exposure increases phytochelatin concentrations in the aquatic snail Lymnaea stagnalis. AB - Phytochelatins are metal-binding metabolites found in almost all plant species and some animal groups, including nematodes and annelids, where they can play an important role in detoxifying metals such as cadmium. Species from several other taxa contain a phytochelatin synthase (PCS) gene orthologue, including molluscs, indicating they may have the potential to synthesize phytochelatins. However, the presence of a gene alone does not demonstrate that it plays a functional role in metal detoxification. In the present study, we show that the aquatic snail Lymnaea stagnalis produced both penta- and heptapeptide phytochelatins (i.e. phytochelatin-2 and phytochelatin-3), and their levels increased in response to sub-lethal levels of cadmium. PMID- 27358198 TI - Prognostic factors after resection of colorectal liver metastases following preoperative second-line chemotherapy: Impact of RAS mutations. AB - BACKGROUND: After resection of colorectal liver metastases (CLM), RAS mutations are associated with modest survival benefit and second-line chemotherapy confers limited hope for cure. OBJECTIVE: To evaluate the impact of RAS mutation after second-line chemotherapy for patients undergoing potentially curative liver resection for CLM. METHODS: Among 1357 patients operated for CLM between January 2005 and November 2014, patients with known RAS mutational status were identified. Outcomes after second-line chemotherapy were analyzed by RAS status. RESULTS: Among 635 patients undergoing resection of CLM, 46 received second-line chemotherapy before resection, including 14 patients (30%) with RAS mutations. Patients who received second-line chemotherapy had significantly larger and greater number of liver metastases and were more likely to undergo major hepatectomy. Median overall (OS) and recurrence free survival (RFS) were significantly worse among patients requiring second-line chemotherapy (OS: 44.4 vs. 61.1 months, p = 0.021; RFS: 7.3 vs. 12.0 months, p = 0.001). Among patients undergoing liver resection after second-line chemotherapy, RAS mutations were associated with worse median OS and RFS (OS: 35.2 vs. 60.7 months, p = 0.038; RFS: 3.6 vs. 8.3 months, p = 0.015). RAS mutation was the only independent factor associated with OS and RFS. All patients with RAS mutations recurred within 18 months. Among patients with RAS wild-type tumors, the receipt of second-line chemotherapy did not affect OS (p = 0.493). CONCLUSION: Among patients undergoing resection of CLM after second-line chemotherapy, RAS mutational status is an independent predictor of survival and outweighs other factors to select patients for liver resection. PMID- 27358199 TI - Maternal and neonatal vitamin-D status in twin versus singleton pregnancies. AB - AIM: There is a paucity of information on vitamin D status of women with twin pregnancy and their newborns. This case-control study compared maternal and neonatal vitamin-D status in twin versus singleton pregnancies. METHODS: Subjects included 50 women with twin pregnancy delivering at >28 weeks and 50 gestational age-matched women with singleton pregnancy delivering during the same period. Maternal and neonatal serum 25-hydroxy vitamin D [25(OH)D] was compared between the two groups using the independent Student's t-test on log values. Serum albumin-adjusted calcium, inorganic phosphate, and intact parathormone levels were also compared. RESULTS: Maternal vitamin-D deficiency (VDD; serum 25(OH)D < 30 nmol/L) was present in 90% of twin and 88% of singleton pregnancies. The prevalence of neonatal VDD was 89% in twin and 74% in singleton pregnancies (P = 0.03). Maternal serum 25(OH)D was lower in the twin group as compared to the singleton group (14.3 +/- 10.47 vs 18.5 +/- 12.36 nmol/L; P = 0.02). Mean serum calcium, intact parathormone, and inorganic phosphate were comparable between the women in the two groups. Maternal and neonatal 25(OH)D showed positive correlation in the two groups (P < 0.001). Mean cord blood 25(OH)D was significantly lower in the twins than in singleton newborns (14.8 +/- 12.63 vs 22.6 +/- 16.68 nmol/L; P = 0.002). The difference persisted even after adjustment for birthweights and maternal serum 25(OH)D. Mean serum calcium was significantly lower in the twins. CONCLUSION: Twin newborns and their mothers have higher VDD as compared to singleton newborns and their mothers in the VDD population. PMID- 27358201 TI - The application of yin-yang concept on heart rate variability patterns in menopausal women with insomnia. AB - OBJECTIVE: To develop heart rate variability (HRV) patterns for peri- and postmenopausal insomnia (PI) by the yin/yang concept of Chinese medicine (CM). METHODS: Seventy-four peri- and postmenopausal women (average age 56.6+/-1.0 years) with insomnia were enrolled in the study. HRV and the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI) were recorded. The Autonomic Nervous System (ANS), Sympathetic and Parasympathetic Indices were derivative from the low frequency (LF), high frequency (HF) and ratio of LF to HF (LF/HF) components of the HRV. A deficiency or the excess pattern for PI was used for ANS index values > 0 or < 0, respectively. The deficiency pattern of PI was further divided into deficiency-yang (ANS index < 0, Sympathetic-Parasympathetic index > 0) and the deficiency-yin patterns (ANS index < 0, Sympathetic-Parasympathetic index < 0). The classification of the excess-yang and the excess-yin patterns of PI was carried out in the same way. The CPSQI and HRV parameters were compared to each of these patterns. RESULTS: The deficiency pattern (60.8 %) occurred more frequently than the excess pattern (39.2%) among PI participants. There were significantly longer bouts of insomnia, prolonged sleep latency, lower LF, HF, and LF/HF of HRV among individuals with the deficiency pattern than among those with the excess pattern among PI participants (P<0.05). The deficiency-yang pattern of PI participants had significantly prolonged sleep latency and decreased sleep efficiency, a higher LF/HF but a lower HF while compared to those with the deficiency-yin pattern (P<0.05). CONCLUSIONS: The results show a possible method of integration of biomedicine and CM by using physiological signals (HRV) combined with the concepts of CM (deficiency/excess and yin/yang) in order to develop diagnostic patterns of PI. This method may be applicable to the trials involving the use of acupuncture or Chinese herbs to treat PI. PMID- 27358202 TI - Model-based evaluation of 5 Chinese medicine recipes in the treatment of H5N1 influenza virus infection in BALB/c mice. AB - OBJECTIVE: To investigate whether Chinese medicine (CM) recipes could ameliorate H5N1 influenza virus infection in BALB/c mice model. METHODS: BALB/c mice were orally administrated with 5 CM recipes (removing toxin, tonifying qi, cooling blood, laxation, and compound recipes), oseltamivir, or saline solution respectively for 5 consecutive days after the infection of H5N1 influenza virus. Series of indices were employed to evaluate the amelioration of the 5 CM recipes on infection, including clinical assessment, gross observation, histopathologic findings, cytokine levels and viral burden in the lungs. RESULTS: Two CM recipes (cooling blood and compound recipes) could postpone the death period of the mice infected with high-dose H5N1 influenza virus (P< 0.05). And for the mice infected with low-dose H5N1 influenza virus, CM recipes could significantly reduce the mortality and inhibit viral proliferation in the lungs as compared with the control group (P<0.05). There was no significant difference in lung coefficients between the treatment and the control groups, but histopathological findings in the lungs were improved in CM recipes groups compared to control group findings. A transient increase was observed in pro-inflammatory and anti-inflammatory cytokines during the first 6 days of infection. The levels of interleukin (IL) 12p40 and interferon-gamma of the treatment groups were significantly lower than that of the control group at day 3 post-infection (P<0.05), while only compound recipe were significantly lower in level of tumor necrosis factor alpha than the control (P<0.05). The level of IL-10 of the control was higher than others, and the differences between the control and cooling blood, removing toxin recipes were significant (P<0.05). CONCLUSIONS: Results of this study suggested the potentials of the CM recipes in ameliorating influenza virus infection by suppressing viral proliferations, improving histopathological lesions, and inhibition of over expression of inflammatory cytokines. PMID- 27358200 TI - High tibial osteotomy in the ACL-deficient knee with medial compartment osteoarthritis. AB - High tibial osteotomy (HTO) has traditionally been used to treat varus gonarthrosis in younger, active patients. Varus malalignment increases the risk of progression of medial compartment osteoarthritis and an HTO can be performed to realign the mechanical axis of the lower limb towards the lateral compartment, thereby decreasing contact pressures in the medial compartment. Anterior cruciate ligament (ACL) insufficiency may lead to post-traumatic arthritis due to altered joint loading and associated injuries to the menisci and articular cartilage. Understanding the importance of posterior tibial slope and its role in sagittal knee stability has led to the development of biplane osteotomies designed to flatten the posterior tibial slope in the ACL deficient knee. Altering the alignment in both the sagittal and coronal planes helps improve stability as well as alter the load in the medial compartment. Detailed history, physical exam and radiographic analysis guide treatment decisions in this high demand patient population. Lateral closing wedge (LCW) and medial opening wedge (MOW) HTOs have been performed and their potential advantages and disadvantages have been well described. Given the triangular shape of the proximal tibia, it is imperative that the surgeon pay close attention to the geometry of the osteotomy "gap" when performing MOW HTO to avoid inadvertently increasing the posterior tibial slope. Simultaneous ACL reconstruction may require technique modifications depending on the type of HTO and ACL graft chosen. With appropriate patient selection and good surgical technique, it is reasonable to expect patients to return to activities of daily living and recreational sports without debilitating pain or instability. PMID- 27358203 TI - Tounong Powder () extracts induce G1 cell cycle arrest and apoptosis in LoVo cells. AB - OBJECTIVE: To further explore the anti-cancer effect of Tounong Powder () extracts (TNSEs) on human colon cancer LoVo cells and examine the possible molecular mechanisms. METHODS: The contents of TNSEs were determined by liquid chromatograph-mass spectrometer (LC-MS) analysis after extraction with water and methanol. Variations of cell morphological features were observed using fluorescence microscopy. Cytotoxicity was determined by the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle distribution and apoptosis were analyzed using flow cytometry at different TNSE doses (0, 62.5, 125, or 250 MUg/mL). Protein expressions of phosphatidylinositol 3-kinase (PI3K), phosphate protein kinase B (p-AKT), phosphate mammalian target of rapamycin (p-mTOR), p-p70s6k1, cleaved caspase-9 and -3 were detected using Western blot analysis. RESULTS: TNSEs induced cell growth inhibition in a concentration- and time-dependent manner. Flow cytometric analysis showed apoptotic cells and cell cycle arrest at the G phase after TNSEs treatment compared with controls. Furthermore, TNSEs significantly down-regulated the proteins PI3K, p-AKT, p-mTOR, and p-p70s6k1, and up-regulated the proteins cleaved caspase-9 and -3 dosedependently, as determined by Western blot. CONCLUSIONS: TNSEs reduced LoVo cell proliferation, and caused apoptosis and cell cycle arrest in LoVo cells. This effect might be associated with regulation of the PI3K/AKT signaling pathway. PMID- 27358204 TI - Pleiotropic effects of herbs characterized with blood-activating and stasis resolving functions on angiogenesis. AB - Accumulative evidences have underpinned the nature candidates from Chinese medicine (CM), particularly CM served as blood activating and stasis resolving (BASR, Huoxue Huayu in Chinese) by targeting tumor-associated angiogenesis. However, recent experiment research on the therapeutic angiogenesis by BASR-CM attracts wide attention and discussion. This opinion review focused on the underlying link between two indications and anticipated that (1) BASR-CM might emphasize on a balanced multi-cytokines network interaction; (2) BASR-CM might address on the nature of diseases prior to differently affecting physiological and pathological angiogenesis; (3) BASR-CM might mainly act on perivascular cells, either promotes arteriogenesis by increasing arteriogenic factors in ischemic diseases, or simultaneously keep a quiescent vasculature to impede angiogenesis in tumor context. PMID- 27358205 TI - Feasibility of an Electronic Survey on iPads with In-Person Data Collectors for Data Collection with Health Care Professionals and Health Care Consumers in General Emergency Departments. AB - BACKGROUND: Translating Emergency Knowledge for Kids was established to bridge the research-practice gap in pediatric emergency care by bringing the best evidence to Canadian general emergency departments (EDs). The first step in this process was to conduct a national needs assessment to determine the information needs and preferences of health professionals and parents in this clinical setting. OBJECTIVE: To describe the development and implementation of two electronic surveys, and determine the feasibility of collecting electronic survey data on iPads with in-person data collectors in a busy clinical environment. METHODS: Two descriptive surveys were conducted in 32 general EDs. Specific factors were addressed in four survey development and implementation stages: survey design, survey delivery, survey completion, and survey return. Feasibility of the data collection approach was determined by evaluating participation rates, completion rates, average survey time to completion, and usability of the platform. Usability was assessed with the in-person data collectors on five key variables: interactivity, portability, innovativeness, security, and proficiency. RESULTS: Health professional participation rates (1561/2575, 60.62%) and completion rates (1471/1561, 94.23%) were strong. Parental participation rates (974/1099, 88.63%) and completion rates (897/974, 92.09%) were excellent. Mean time to survey completion was 28.08 minutes for health professionals and 43.23 minutes for parents. Data collectors rated the platform "positively" to "very positively" on all five usability variables. CONCLUSIONS: A number of design and implementation considerations were explored and integrated into this mixed-mode survey data collection approach. Feasibility was demonstrated by the robust survey participation and completion rates, reasonable survey completion times, and very positive usability evaluation results. PMID- 27358206 TI - Single vessel air injection estimates of xylem resistance to cavitation are affected by vessel network characteristics and sample length. AB - Xylem resistance to cavitation is an important trait that is related to the ecology and survival of plant species. Vessel network characteristics, such as vessel length and connectivity, could affect the spread of emboli from gas-filled vessels to functional ones, triggering their cavitation. We hypothesized that the cavitation resistance of xylem vessels is randomly distributed throughout the vessel network. We predicted that single vessel air injection (SVAI) vulnerability curves (VCs) would thus be affected by sample length. Longer stem samples were predicted to appear more resistant than shorter samples due to the sampled path including greater numbers of vessels. We evaluated the vessel network characteristics of grapevine (Vitis vinifera L.), English oak (Quercus robur L.) and black cottonwood (Populus trichocarpa Torr. & A. Gray), and constructed SVAI VCs for 5- and 20-cm-long segments. We also constructed VCs with a standard centrifuge method and used computer modelling to estimate the curve shift expected for pathways composed of different numbers of vessels. For all three species, the SVAI VCs for 5 cm segments rose exponentially and were more vulnerable than the 20 cm segments. The 5 cm curve shapes were exponential and were consistent with centrifuge VCs. Modelling data supported the observed SVAI VC shifts, which were related to path length and vessel network characteristics. These results suggest that exponential VCs represent the most realistic curve shape for individual vessel resistance distributions for these species. At the network level, the presence of some vessels with a higher resistance to cavitation may help avoid emboli spread during tissue dehydration. PMID- 27358207 TI - Implication of the suberin pathway in adaptation to waterlogging and hypertrophied lenticels formation in pedunculate oak (Quercus robur L.). AB - Waterlogging causes stressful conditions for perennial species. The temporary overabundance of water in waterlogged soil can induce hypoxia in the rhizosphere, leading to root death, tree decline and even dieback. Two closely related members of the European white oak complex, pedunculate (Quercus robur L.) and sessile (Quercus petraea Matt. Liebl.) oaks, have different ecological characteristics, especially regarding their adaptation to soil waterlogging. The tolerance of waterlogging observed in pedunculate oak is driven principally by its ability to produce adaptive structures, hypertrophied lenticels and adventitious roots, and to switch rapidly its metabolism to the fermentative pathway. This study had two objectives: (i) to identify genes important for adaptation to waterlogging and (ii) to gain insight into the molecular mechanisms involved in hypertrophied lenticel formation in pedunculate oak. We subjected seedlings of the two species to hypoxia by maintaining the water level 2 cm above the collar. The immersed part of the stem (i.e., containing hypertrophied lenticels in pedunculate oak) was sampled after 9 days of waterlogging stress and its gene expression was investigated by RNA-seq. Genes displaying differential expression between the two species were identified with the DESeq R package and a false discovery rate of 0.001. We found that 3705 contigs were differentially regulated between the two species. Twenty-two differentially expressed genes were validated by real-time quantitative polymerase chain reaction. The suberin biosynthesis pathway was found to be upregulated in pedunculate oak, consistent with molecular mechanisms analogous to those operating in the radial oxygen loss barrier in waterlogging tolerant species. PMID- 27358208 TI - David Oliver: The forgotten problem of incontinence. PMID- 27358209 TI - Dispersal behavior of yellowjacket (Vespula germanica) queens. AB - Understanding the factors that affect animal dispersal behavior is important from both fundamental and applied perspectives. Dispersal can have clear evolutionary and ecological consequences, but for nonnative insect pests, dispersal capacity can also help to explain invasion success. Vespula germanica is a social wasp that, in the last century, has successfully invaded several regions of the world, showing one of the highest spread rates reported for a nonnative insect. In contrast with nonsocial wasps, in social species, queens are responsible for population redistribution and spread, as workers are sterile. For V. germanica, it has been observed that queen flight is limited to 2 distinct periods: early autumn, when new queens leave the nest to mate and find sheltered places in which to hibernate, and spring when new colonies are founded. Our aim was to study the flight behavior of V. germanica queens by focusing on the different periods in which dispersal occurs, characterizing as well the potential contribution of queen flight (i.e., distance) to the observed geographical spread. Our results suggest that the distances flown by nonoverwintered queens is greater than that flown by overwintered individuals, suggesting that the main queen dispersal events would occur before queens enter hibernation. This could relate to a behavioral trait of the queens to avoid the inbreeding with related drones. Additionally, given the short distances flown and remarkable geographical spread observed, we provide evidence showing that queen dispersal by flight is likely to contribute proportionately less to population spread than human-aided factors. PMID- 27358210 TI - Long-term clinical safety and efficacy of brodalumab in the treatment of Japanese patients with moderate-to-severe plaque psoriasis. AB - BACKGROUND: Brodalumab (KHK4827) is a human anti-interleukin-17-receptor A monoclonal antibody. In Japanese patients with moderate-to-severe plaque psoriasis, brodalumab showed rapid and robust efficacy and a favourable safety profile in a 12-week, phase 2, double-blind, randomized controlled trial. OBJECTIVES: To evaluate the long-term safety and efficacy of brodalumab, an extension of a phase 2 trial of Japanese patients with moderate-to-severe psoriasis was performed. METHODS: Patients received open-label brodalumab 210 or 140 mg subcutaneously every 2 weeks for 52 weeks. Efficacy was measured using the Psoriasis Area and Severity Index (PASI) score and the static physician global assessment (sPGA) instrument. The endpoint of psoriatic arthritis was 20% improvement in American College of Rheumatology response criteria (ACR 20). The patients were also monitored for treatment-emergent adverse events (AEs), including serious AEs (SAEs). RESULTS: Of 145 patients, 133 completed the study. The percentage of patients with >=75% reduction of PASI scores (PASI 75), >=90% (PASI 90) and 100% (PASI 100) at Week 52 (the last observation carried forward) were 94.4%, 87.5% and 55.6%, respectively, in the 210-mg group, and the corresponding values in the 140-mg group were 78.1%, 71.2% and 43.8%. At Week 52, 75.0% patients in 210-mg group achieved ACR 20, compared with 37.5% patients in 140-mg group. The most commonly reported AEs were nasopharyngitis (35.2%), upper respiratory tract inflammation (10.3%) and contact dermatitis (9.7%). CONCLUSION: Brodalumab showed a sustained clinical response and an acceptable safety profile through 52 weeks in Japanese patients with moderate-to-severe plaque psoriasis in this open-label extension study. PMID- 27358212 TI - Ranolazine Therapy in Cardiac Arrhythmias. AB - Ranolazine is an antianginal medication originally granted approval by the U.S. Food and Drug Administration for therapeutic use in 2006. Since its introduction into the U.S. market, there have been multiple trials and clinical case reports that demonstrate ranolazine may be effective in the prevention and treatment of both atrial and ventricular arrhythmias, including postoperative atrial fibrillation following coronary artery bypass graft (CABG) surgery. More recently, the combination of dronedarone with ranolazine has demonstrated in initial studies to have a synergistic effect in the reduction of burden of atrial fibrillation. This article will review the basic pharmacology of ranolazine, the studies demonstrating use of ranolazine in atrial and ventricular arrhythmias, the limitations to the use of ranolazine as antiarrhythmic therapy, and explore the synergistic effect with other agents in the suppression of arrhythmias. PMID- 27358213 TI - Extranasal Staphylococcus aureus colonization predisposes to bloodstream infections in patients on hemodialysis with noncuffed internal jugular vein catheters. AB - INTRODUCTION: Staphylococcal infection of endogenous origin is an important cause of morbidity and mortality in patients who receive hemodialysis (HD). The risk of such infections in nasal carriers of the organism is well defined. Extranasal carriage of the organism at extranasal sites may pose similar risks. METHODS: A total of 70 patients about to undergo internal jugular vein catheterization for HD were enrolled in this prospective observational study. Swab cultures were obtained from anterior nares, posterior pharynx, axillae, toe web spaces, and vascular access sites at baseline and 1 week later. A patient was defined as a persistent carrier when the same organism was grown in both samples. Staphylococcus aureus bloodstream infections were assessed by blood and catheter tip cultures over a 90-day period. FINDINGS: The mean age of the patients was 43.71 +/- 16.2 years. Persistent S. aureus carriage at anterior nares, throat, axilla, toe web spaces, vascular access site, and all sites was documented in 27.9%, 11.4%, 40%, 32.9%, 4.3%, and 64.2% of patients, respectively. Fifteen patients developed S. aureus infections. Catheter related S. aureus infections (CRI) were more likely in persistent carriers than nonpersistent carriers with odds ratios (95% CI) of 10.2 (2.8-37.1), 8.6 (1.7-42.2), 17.3 (3.4-86.0), 3.0 (0.9-9.8), and 1.9 (0.2-22.4) for anterior nares, throat, axilla, toe web spaces, and vascular access site carriers, respectively. The probability of developing CRI in persistent S. aureus carriers was 55% compared to none in noncarriers at 90 days (P = 0.04). DISCUSSION: Extranasal S. aureus carriage is as significant a risk factor as nasal carriage for staphylococcal infections in patients on HD through catheters. The study is limited by lack of molecular phenotyping. PMID- 27358211 TI - CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study. AB - Approximately 10% to 20% of patients optimally treated for early Lyme disease develop persistent symptoms of unknown pathophysiology termed posttreatment Lyme disease syndrome (PTLDS). The objective of this study was to investigate associations between PTLDS and immune mediator levels during acute illness and at several time points following treatment. Seventy-six participants with physician documented erythema migrans and 26 healthy controls with no history of Lyme disease were enrolled. Sixty-four cytokines, chemokines, and inflammatory markers were measured at each visit for a total of 6 visits over 1 year. An operationalized definition of PTLDS incorporating symptoms and functional impact was applied at 6 months and 1 year following treatment completion, and clinical outcome groups were defined as the return-to-health, symptoms-only, and PTLDS groups. Significance analysis of microarrays identified 7 of the 64 immune mediators to be differentially regulated by group. Generalized logit regressions controlling for potential confounders identified posttreatment levels of the T cell chemokine CCL19 to be independently associated with clinical outcome group. Receiver operating characteristic analysis identified a CCL19 cutoff of >111.67 pg/ml at 1 month following treatment completion to be 82% sensitive and 83% specific for later PTLDS. We speculate that persistently elevated CCL19 levels among participants with PTLDS may reflect ongoing, immune-driven reactions at sites distal to secondary lymphoid tissue. Our findings suggest the relevance of CCL19 both during acute infection and as an immunologic risk factor for PTLDS during the posttreatment phase. Identification of a potential biomarker predictor for PTLDS provides the opportunity to better understand its pathophysiology and to develop early interventions in the context of appropriate and specific clinical information. PMID- 27358214 TI - Development and Evaluation of a Smartphone-Based Measure of Social Rhythms for Bipolar Disorder. AB - Dynamic psychological processes are most often assessed using self-report instruments. This places a constraint on how often and for how long data can be collected due to the burden placed on human participants. Smartphones are ubiquitous and highly personal devices, equipped with sensors that offer an opportunity to measure and understand psychological processes in real-world contexts over the long term. In this article, we present a novel smartphone approach to address the limitations of self-report in bipolar disorder where mood and activity are key constructs. We describe the development of MoodRhythm, a smartphone application that incorporates existing self-report elements from interpersonal and social rhythm therapy, a clinically validated treatment, and combines them with novel inputs from smartphone sensors. We reflect on lessons learned in transitioning from an existing self-report instrument to one that involves smartphone sensors and discuss the potential impact of these changes on the future of psychological assessment. PMID- 27358215 TI - Transient acantholytic dyskeratosis (Grover's disease) after bone marrow transplantation. AB - Cutaneous eruptions in recipients of allogeneic haematopoietic stem cell transplantation (AHSCT) are frequent, and common aetiologies include graft-versus host disease (GVHD), drug reactions, viral infections and engraftment syndrome. Transient acantholytic dermatosis or Grover's disease has been described in oncology patients and it is rarely reported after AHSCT. However, this benign and self-limiting condition should be histologically distinguished from other, more serious entities, mainly stage IV GVHD, in order to avoid inappropriate treatment with corticosteroids and intensive immunosuppression. PMID- 27358216 TI - CrossTalk opposing view: Sleep apnoea causes metabolic syndrome. PMID- 27358217 TI - The cerebral venous system in migraine: the not so innocent bystander? PMID- 27358218 TI - Lower- and higher-level models of right hemisphere language. A selective survey. AB - The models advanced to explain right hemisphere (RH) language function can be divided into two main types. According to the older (lower-level) models, RH language reflects the ontogenesis of conceptual and semantic-lexical development; the more recent models, on the other hand, suggest that the RH plays an important role in the use of higher-level language functions, such as metaphors, to convey complex, abstract concepts. The hypothesis that the RH may be preferentially involved in processing the semantic-lexical components of language was advanced by Zaidel in splitbrain patients and his model was confirmed by neuropsychological investigations, proving that right brain-damaged patients show selective semanticlexical disorders. The possible links between lower and higher levels of RH language are discussed, as is the hypothesis that the RH may have privileged access to the figurative aspects of novel metaphorical expressions, whereas conventionalization of metaphorical meaning could be a bilaterally mediated process involving abstract semantic-lexical codes. PMID- 27358219 TI - Vestibular disorders following different types of head and neck trauma. AB - This review focuses on the published literature on vestibular disorders following different types of head and neck trauma. Current knowledge of the different causes and underlying mechanisms of vestibular disorders, as well as the sites of organic damage, is presented. Non-organic mechanisms are also surveyed. The frequency of occurrence of vestibular symptoms, and of other accompanying subjective complaints, associated with different types of trauma is presented and related to the specific causes. Hypotheses about the pathogenesis of traumatic vestibular disorders are presented, and the knowledge derived from animal experiments is also discussed. We believe this to be a very important topic, since vestibular complaints in traumatic patients often remain undiagnosed or underestimated in clinical practice. This review article aims to suggest directions for additional research and to provide guidance to both the scientific and clinical practice communities. PMID- 27358220 TI - Cerebral venous hemodynamic abnormalities in episodic and chronic migraine. AB - Alterations of cerebral venous drainage have been demonstrated in chronic migraine (CM), suggesting that cerebral venous hemodynamic abnormalities (CVHAs) play a role in this condition. The aim of the present study was to look for a correlation between CM and CVHAs. We recruited 33 subjects suffering from CM with or without analgesic overuse, 29 episodic migraine (EM) patients with or without aura, and 21 healthy subjects as controls (HCs). CVHAs were evaluated by transcranial and extracranial echo-color Doppler evaluation of five venous hemodynamic parameters. CVHAs were significantly more frequent in the CM and EM patients than in the HCs. In the migraine patients, CVHAs were not correlated with clinical features. The significantly greater frequency of CVHAs observed in the migraineurs may reflect a possible relationship between migraine and these abnormalities. Prospective longitudinal studies are needed to investigate whether CVHAs have a role in the processes of migraine chronification. PMID- 27358221 TI - Antiepileptic drug use in a nursing home setting: a retrospective study in older adults. AB - The authors set out to examine qualitatively the use of antiepileptic drugs (AEDs) in a population of older adults in a nursing home setting, evaluating aspects such as specialist prescriptions and changes in dosage. This retrospective prevalence study was carried out in a state-funded nursing home that provides care and rehabilitation for elderly people. The first objective of the study was to determine the prevalence of AED use in this population. The second objective was to monitor AED dosage modifications during the fifteen-month study period, focusing on the safety and the tolerability of AEDs. In the period of time considered, 129 of 402 monitored patients received at least one anti epileptic therapy. The prevalence of AED use was therefore 32%. Gabapentin was found to be the most commonly prescribed drug, with a frequency of 29%, and it was used mainly for anxiety disorders, psychosis, neuropathic pain and mood disorders. PMID- 27358222 TI - Delayed auditory conduction in diabetes: is metformin-induced vitamin B12 deficiency responsible? AB - The present study aims to evaluate the functional integrity of the auditory pathway in patients with diabetes taking metformin. A further aim is to assess its association with vitamin B12 deficiency induced by metformin. Thirty diabetics taking metformin and 30 age-matched non-diabetic controls were enrolled. Stimulus-related potentials and vitamin B12 levels were evaluated in all the subjects. The diabetics showed deficient vitamin B12 levels and delayed wave III latency and III-V interpeak latency in the right ear and delayed Na and Pa wave latencies in the left ear compared with the controls. The dose and duration of metformin showed no association with the stimulusrelated potentials. Therefore, although vitamin B12 levels were deficient and auditory conduction impairment was present in the diabetics on metformin, this impairment cannot be attributed to the vitamin B12 deficiency. PMID- 27358223 TI - Cerebrospinal fluid analysis after unprovoked first seizure. AB - The aim of this study was to determine cerebrospinal fluid (CSF) characteristics after an unprovoked first seizure (UFS). We reviewed the medical records of 71 patients with UFS who underwent lumbar puncture, and examined the CSF parameters. Each CSF parameter was evaluated separately for potential correlations with the other study variables. We observed an overall frequency of CSF abnormalities of 35.2%. CSF protein was the most common abnormal parameter (31%) and showed significant positive correlations with male gender (p=0.037) and older age (p=0.007). Only seven patients (9.9%) had an abnormal cell count (5-40 cells/MUl). Higher CSF cell counts were found to predict a longer hospitalization period (p=0.005). No relationship with abnormal EEG findings could be established (p=0.169). This study is one of the few to evaluate postictal CSF parameters in a clinical setting, and to our knowledge the first to investigate these parameters specifically in the emergency department. The development of a rapid, easy-to-use test that does not require extensive laboratory equipment to differentiate UFS from other conditions could be of great value in everyday clinical practice. PMID- 27358224 TI - Outcomes of a multicomponent intervention on occupational performance in persons with unilateral acquired brain injury. AB - Complications after unilateral acquired brain injury (ABI) can affect various areas of expertise causing (depending on the location of the lesion) impairment in occupational performance. The aim of this study was to analyze and compare the concepts of occupational performance and functional independence, both before and after a multicomponent intervention including occupational therapy, in persons with unilateral brain damage. This was a longitudinal quasi-experimental pretest post-test study in a sample of 58 patients with unilateral brain injury (28 with traumatic brain injury and 30 with ischemic stroke). The patients' level of independence was measured using the short version of the International Classification of Functioning, Disability and Health. We also measured quality of performance using the Assessment of Motor and Process Skills. The findings of this study showed that patients with injury in the right hemisphere improved more than those with left hemisphere damage (p<0.001). All the patients with ABI, especially those with right-sided injury, derived benefit from the multicomponent intervention, except in the area of motor skills. More research is needed on the specific techniques that might address such skills. PMID- 27358225 TI - Clinical effects of non-invasive cerebellar magnetic stimulation treatment combined with neuromotor rehabilitation in traumatic brain injury. A single case study. AB - Multimodal treatments are emerging as effective approaches for motor recovery in traumatic brain injury (TBI). Various evidence has demonstrated that repetitive transcranial magnetic stimulation (rTMS) may improve outcomes in people with motor disorders. Behavioral gains from rTMS protocols may be maximized when brain stimulation is coupled with carefully designed occupational/physical therapy. We present the case of a 25-year-old man with chronic TBI (a bilateral corticosubcortical parieto-occipital lesion) who underwent three weeks of cerebellar intermittent theta burst stimulation (iTBS), a form of rTMS, combined with neurorehabilitation treatment. The Fugl-Meyer Assessment (FMA), Berg Balance Scale (BBS), Jebsen-Taylor Hand Function Test, and accelerometer gait analysis were administered before and after treatment. The results showed improvements in balance performance (BBS: T0=47; T1=53; +10.72%), motor recovery (FMA: T0=93/100; T1=96/100; +3.00%), step length (T0=50.4+/-7.2; T1=53.8+/-2.2 cm, p<0.001), and walking speed (T0=0.87+/-0.06; T1=0.91+/-0.04 m/sec,p<0.001). Combined cerebellar rTMS and neurore-Clinical effects of non-invasive cerebellar magnetic stimulation treatment combined with neuromotor rehabilitation in traumatic brain injury. A single case study. habilitation seems to be a promising treatment for motor and balance dysfunctions in TBI patients. PMID- 27358226 TI - Vertically Conductive MoS2 Spiral Pyramid. AB - MoS2 spirals grown by the chemical vapor deposition method, driven by a threading dislocation, has a peculiar rhombohedral-like structure. This threading dislocation can carry helical current in the vertical direction and greatly enhances the vertical conductance in the MoS2 multilayer samples. PMID- 27358227 TI - GI-Safer Aspirin: Sometimes Sugar Coating Helps. PMID- 27358228 TI - Prediction of the Risk of a Metachronous Advanced Colorectal Neoplasm Using a Novel Scoring System. AB - BACKGROUND AND AIM: This study aimed to develop and validate a risk score model to estimate the probability of a metachronous advanced colorectal neoplasm (ACRN) at surveillance colonoscopy. METHODS: A retrospective analysis of a prospectively obtained database of 11,042 asymptomatic subjects who underwent surveillance colonoscopy after a screening colonoscopy was conducted. Subjects were randomly divided into derivation (n = 7730) and validation sets (n = 3312). From the derivation cohort, risk factors for a metachronous ACRN were identified by a multivariable analysis. Risk points were allocated to each risk factor based on the hazard ratio to develop the Metachronous Advanced colorectal neoplasm Prediction Scoring (MAPS) model, the performance of which was assessed in the validation cohort. RESULTS: In the derivation cohort, age, male, sessile serrated adenoma/polyp, and a high-risk CRN (ACRN or >=3 adenomas) at screening colonoscopy were independent risk factors for a metachronous ACRN. These variables were incorporated into the MAPS model, and the risk score ranged 0-17 (high MAPS risk arbitrarily defined as 10-17). At the 3-year surveillance colonoscopy, ACRN was found in 5.1 % of the high MAPS risk group versus 3.9 % of the high-risk CRN group. The colonoscopy number needed to detect one metachronous ACRN at the 3-year surveillance was 19.5 (95 % CI 11.7-33.2) for the high MAPS risk group versus 25.8 (95 % CI 15.4-44.0) for the high-risk CRN group. These findings were similarly confirmed in the validation cohort. CONCLUSIONS: Our MAPS model based on clinical and colonoscopic parameters effectively predicts the risk of a metachronous ACRN. PMID- 27358230 TI - Implementation of a structured hospital-wide morbidity and mortality rounds model. AB - IMPORTANCE: There is a paucity of literature on the quality and effectiveness of institutional morbidity & mortality (M&M) rounds processes. OBJECTIVE: We sought to implement and evaluate the effectiveness of a hospital-wide structured M&M rounds model at improving the quality of M&M rounds across multiple specialties. DESIGN, SETTING, PARTICIPANTS: We conducted a prospective interventional study involving 24 clinical groups (1584 physicians) at a tertiary care teaching hospital from January 2013 to June 2015. INTERVENTION: We implemented the published Ottowa M&M Model (OM3): appropriate case selection, cognitive/system issues analyses, interprofessional participation, dissemination of lessons and effector mechanisms. MAIN OUTCOMES AND MEASURES: We created an OM3 scoring index reflecting these elements to measure the quality of M&M rounds. Secondary outcomes include explicit discussions of cognitive/system issues and resultant action items. RESULTS: OM3 scores for all participating groups improved significantly from a median of 12.0/24 (95% CI 10 to 14) to 20.0/24 (95% CI 18 to 21). An increased frequency of in-rounds discussion around cognitive biases (pre 154/417 (37%), post 256/466 (55%); p<0.05) and system issues (pre 175/417 (42%), post 259/466 (62%); p<0.05) were reported by participants via online surveys postintervention, while in-person surveys throughout the intervention period demonstrated even higher frequencies (cognitive biases 1222/1437 (85%); system issues 1250/1437 (87%)). We found 45 action items resulting directly from M&M rounds postintervention, compared with none preintervention. CONCLUSIONS AND RELEVANCE: Implementation of a structured model enhanced the quality of M&M rounds with demonstrable policy improvements hospital wide. The OM3 can be feasibly implemented at other hospitals to effectively improve quality of M&M rounds across different specialties. PMID- 27358231 TI - Channels and Volume Changes in the Life and Death of the Cell. AB - Volume changes deviating from original cell volume represent a major challenge for cellular homeostasis. Cell volume may be altered either by variations in the external osmolarity or by disturbances in the transmembrane ion gradients that generate an osmotic imbalance. Cells respond to anisotonicity-induced volume changes by active regulatory mechanisms that modify the intracellular/extracellular concentrations of K(+), Cl(-), Na(+), and organic osmolytes in the direction necessary to reestablish the osmotic equilibrium. Corrective osmolyte fluxes permeate across channels that have a relevant role in cell volume regulation. Channels also participate as causal actors in necrotic swelling and apoptotic volume decrease. This is an overview of the types of channels involved in either corrective or pathologic changes in cell volume. The review also underlines the contribution of transient receptor potential (TRP) channels, notably TRPV4, in volume regulation after swelling and describes the role of other TRPs in volume changes linked to apoptosis and necrosis. Lastly we discuss findings showing that multimers derived from LRRC8A (leucine-rich repeat containing 8A) gene are structural components of the volume-regulated Cl(-) channel (VRAC), and we underline the intriguing possibility that different heteromer combinations comprise channels with different intrinsic properties that allow permeation of the heterogenous group of molecules acting as organic osmolytes. PMID- 27358229 TI - Wisteria floribunda agglutinin-sialylated mucin core polypeptide 1 is a sensitive biomarker for biliary tract carcinoma and intrahepatic cholangiocarcinoma: a multicenter study. AB - BACKGROUND: Wisteria floribunda agglutinin (WFA)-sialylated mucin core polypeptide 1 (MUC1) was investigated as a new glycoprotein marker for cholangiocarcinoma (CC) using glycoproteomics technologies. In this multicenter study, WFA-sialylated MUC1 levels in serum and bile samples were measured to determine their diagnostic capability in biliary tract carcinoma (BTC) and intrahepatic (Ih) CC. METHODS: The study included 244 patients with BTC, 59 patients with IhCC, 287 patients with benign biliary tract diseases, and 44 control subjects. RESULTS: Serum WFA-sialylated MUC1 levels were significantly higher in patients with either BTC or IhCC than in control subjects and those with benign biliary tract diseases. Patients with IhCC showed higher WFA sialylated MUC1 levels than patients with tumors at other sites. No significant differences in WFA-sialylated MUC1 levels were found with regard to cancer stage or tissue type. Receiver operating characteristic curve analysis showed that WFA sialylated MUC1 was superior to carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) for the diagnosis of benign biliary tract diseases, BTC, and IhCC, as well as for stage I and II carcinomas. Significantly higher levels of biliary WFA-sialylated MUC1 were observed in BTC/IhCC than in benign biliary tract diseases. The diagnostic capability of biliary WFA sialylated MUC1 was also superior to that of CA19-9, and diagnostic sensitivity was higher than that of biliary cytology for BTC/IhCC. CONCLUSIONS: WFA sialylated MUC1 is a useful novel biomarker for BTC/IhCC. In the future, this measurement should be applied in the clinical setting. PMID- 27358232 TI - Quantitative Single-Cell Analysis of Signaling Pathways Activated Immediately Downstream of Histamine Receptor Subtypes. AB - Genetically encoded biosensors based on Forster resonance energy transfer (FRET) can visualize responses of individual cells in real time. Here, we evaluated whether FRET-based biosensors provide sufficient contrast and specificity to measure activity of G-protein-coupled receptors. The four histamine receptor subtypes (H1R, H2R, H3R, and H4R) respond to the ligand histamine by activating three canonical heterotrimeric G-protein-mediated signaling pathways with a reported high degree of specificity. Using FRET-based biosensors, we demonstrate that H1R activates Galphaq. We also observed that H1R activates Galphai, albeit at a 10-fold lower potency. In addition to increasing cAMP levels, most likely via Galphas, we found that the H2R induces Galphaq-mediated calcium release. The H3R and H4R activated Galphai with high specificity and a high potency. We demonstrate that a number of FRET sensors provide sufficient contrast to: 1) analyze the specificity of the histamine receptor subtypes for different heterotrimeric G-protein families with single-cell resolution, 2) probe for antagonist specificity, and 3) allow the measurement of single-cell concentration response curves. PMID- 27358233 TI - In vitro hepatotoxicity of 'Legal X': the combination of 1-benzylpiperazine (BZP) and 1-(m-trifluoromethylphenyl)piperazine (TFMPP) triggers oxidative stress, mitochondrial impairment and apoptosis. AB - N-Benzylpiperazine (BZP) and 1-(3-trifluoromethylphenyl)piperazine (TFMPP) are two synthetic phenylpiperazine analogues that have been frequently commercialized in combination as an alternative to ecstasy ('Legal X'). Despite reports of several clinical complications following the use of these drugs in association, few studies have been conducted so far to elucidate their combined toxicity. The present study was aimed at clarifying the cytotoxic effects of mixtures of BZP and TFMPP in vitro. Human-derived HepaRG cells and primary rat hepatocytes were exposed to the drugs, individually or combined at different mixture ratios, and cytotoxicity was assessed by the MTT assay. Mixture additivity expectations were calculated by the independent action and the concentration addition (CA) models and compared with the experimental outcomes. To delineate the mechanisms underlying the elicited effects, a range of stress endpoints was evaluated, including oxidative stress, energetic imbalance, and metabolic interactions. It was observed that primary rat hepatocytes are more sensitive than HepaRG cells to the toxicity of BZP (EC50 2.20 and 6.60 mM, respectively) and TFMPP (EC50 0.14 and 0.45 mM, respectively). For all BZP-TFMPP combinations tested, CA was the most appropriate model to predict the mixture effects. TFMPP proved to act additively with BZP to produce significant hepatotoxicity (p < 0.01). Remarkably, substantial mixture effects were observed even when each drug was present at concentrations that were harmless individually. In primary hepatocytes, a small deviation from additivity (antagonism) was observed toward the upper range of the concentration-response curve. GC/MS data suggest that a metabolic interaction may be at a play, as the mixture favors the metabolism of both substances, to a significant extent in the case of BZP (p < 0.05). Also, our results demonstrate the influence of oxidative stress and energetic imbalance on these effects (increase in RNS and ROS production, decrease in intracellular GSH/GSSG, ATP depletion and mitochondrial Deltapsim disruption). The present work clearly demonstrates that potentially harmful interactions among BZP and TFMPP are expected when these drugs are taken concomitantly. PMID- 27358234 TI - High-content imaging-based BAC-GFP toxicity pathway reporters to assess chemical adversity liabilities. AB - Adaptive cellular stress responses are paramount in the healthy control of cell and tissue homeostasis and generally activated during toxicity in a chemical specific manner. Here, we established a platform containing a panel of distinct adaptive stress response reporter cell lines based on BAC-transgenomics GFP tagging in HepG2 cells. Our current panel of eleven BAC-GFP HepG2 reporters together contains (1) upstream sensors, (2) downstream transcription factors and (3) their respective target genes, representing the oxidative stress response pathway (Keap1/Nrf2/Srxn1), the unfolded protein response in the endoplasmic reticulum (Xbp1/Atf4/BiP/Chop) and the DNA damage response (53bp1/p53/p21). Using automated confocal imaging and quantitative single-cell image analysis, we established that all reporters allowed the time-resolved, sensitive and mode-of action-specific activation of the individual BAC-GFP reporter cell lines as defined by a panel of pathway-specific training compounds. Implementing the temporal pathway activity information increased the discrimination of training compounds. For a set of >30 hepatotoxicants, the induction of Srxn1, BiP, Chop and p21 BAC-GFP reporters correlated strongly with the transcriptional responses observed in cryopreserved primary human hepatocytes. Together, our data indicate that a phenotypic adaptive stress response profiling platform will allow a high throughput and time-resolved classification of chemical-induced stress responses, thus assisting in the future mechanism-based safety assessment of chemicals. PMID- 27358235 TI - Sirtuin 1-dependent resveratrol cytotoxicity and pro-differentiation activity on breast cancer cells. AB - Sirtuins regulate several processes associated with tumor development. Resveratrol was shown to stimulate sirtuin 1 and 3 (SIRT1/3) activities and to result in cytotoxicity for some tumor types. The relationship between modulation of sirtuin activities, cellular metabolic remodeling and resveratrol cytotoxicity mechanism on breast cancer cells is still an open question. Here, we evaluated whether sirtuin 1 and 3 are involved in resveratrol toxicity and whether resveratrol leads to a metabolic remodeling and cell differentiation. Results using the Extracellular Flux Analyzer indicated that resveratrol inhibits mitochondrial respiration in breast cancer cells. We also demonstrated here for the first time that resveratrol cytotoxic effects on breast cancer cells were modulated by SIRT1 and also involved mitochondrial complex I inhibition. Importantly, we also demonstrated that resveratrol reduced the pool of breast cancer cells with stemness markers through a SIRT1-dependent mechanism. Our data highlights the role of SIRT1 in regulating resveratrol induced differentiation and/or toxicity in breast cancer cells. PMID- 27358236 TI - Pseudocatalytic scavenging of the nerve agent VX with human blood components and the oximes obidoxime and HI-6. AB - Despite six decades of extensive research in medical countermeasures against nerve agent poisoning, a broad spectrum acetylcholinesterase (AChE) reactivator is not yet available. One current approach is directed toward synthesizing oximes with high affinity and reactivatability toward butyrylcholinesterase (BChE) in plasma to generate an effective pseudocatalytic scavenger. An interim solution could be the administration of external AChE or BChE from blood products to augment pseudocatalytic scavenging with slower but clinically approved oximes to decrease nerve agent concentrations in the body. We here semiquantitatively investigate the ability of obidoxime and HI-6 to decrease the inhibitory activity of VX with human AChE and BChE from whole blood, erythrocyte membranes, erythrocytes, plasma, clinically available fresh frozen plasma and packed red blood cells. The main findings are that whole blood showed a VX concentration dependent decrease in inhibitory activity with HI-6 being more potent than obidoxime. Using erythrocytes and erythrocyte membranes again, HI-6 was more potent compared to obidoxime. With freshly prepared plasma, obidoxime and HI-6 showed comparable results for the decrease in VX. The use of the clinically available blood products revealed that packed red blood cells showed similar kinetics as fresh erythrocytes. Fresh frozen plasma resulted in a slower and incomplete decrease in inhibitory plasma compared to freshly prepared plasma. In conclusion, the administration of blood products in combination with available oximes augments pseudocatalytic scavenging and might be useful to decrease the body load of persistent, highly toxic nerve agents. PMID- 27358237 TI - Phtalates: new cardiovascular health disruptors? AB - Phtalates are commonly found in several household products such as food packaging, furniture and toys. Humans are exposed to phtalates through different ways such as inhalation, ingestion and dermal contact. Due to the abundance of plastic in our society, the exposure to phtalates is ubiquitous. A growing body of evidence investigated the association of phtalate exposure with cardiovascular risk factors, i.e., obesity, type 2 diabetes and hypertension. Phtalates are thought to contribute to obesity through their binding and activation of PPARgamma receptor that in turn results in the upregulation of adipocyte production. Phtalates are also known to interfere with insulin signaling and to increase oxidative stress. All these mechanisms contribute to the onset of insulin resistance. Recent evidences support a role of phtalates in the pathogenesis of atherosclerosis and hypertension. Thus, the aim of this communication was to summarize the current evidences dealing with the association of phtalates and cardiovascular risk factors. PMID- 27358238 TI - Erratum to: Assessing the potential impact on the thyroid axis of environmentally relevant food constituents/contaminants in humans. PMID- 27358239 TI - Toxicological Evaluation of beta-Caryophyllene Oil: Subchronic Toxicity in Rats. AB - In a subchronic toxicity study, administration of beta-caryophyllene (BCP) oil by oral gavage to Wistar rats at dosages of 0, 150, 450, or 700 mg/kg/d for 90 days, including a 21-day recovery period, did not produce any significant toxicologic manifestations. The study design also included a 28-day interim sacrifice in the control and high-dose groups. The BCP oil test article was well tolerated as evidenced by the absence of major treatment-related changes in the general condition and appearance of the rats, neurobehavioral end points, growth, feed and water intake, ophthalmoscopic examinations, routine hematology and clinical chemistry parameters, urinalysis, and necropsy findings. The no observed adverse effect level was the highest dosage level administered of 700 mg/kg body weight/d for both male and female rats. The study was conducted as part of an investigation to examine the safety of BCP oil for its proposed use in medical food products. PMID- 27358240 TI - Fast and Efficient Transfection of Mouse Embryonic Stem Cells Using Non-Viral Reagents. AB - Reliable and efficient DNA and RNA transfection methods are required when studying the role of individual genes in mouse pluripotent stem cells. However, these cells usually grow in tight clusters and are therefore more difficult to transfect than many other cell lines. We have found that transfection is especially challenging when mouse embryonic stem (mES) cells are cultured in the newly described 2i medium, which is based on two chemical inhibitors of differentiation pathways. In the present study we have performed a side-by-side comparison of commercially available, non-viral transfection reagents with regard to their ability to deliver plasmid DNA and siRNA into adherent and/or trypsinized mES cells cultured in 2i medium, assessing transfection rates, plasmid gene expression, siRNA mediated knockdown of Oct4 and viability. Finally, we present a fast and efficient method for transfection of trypsinized mES cells using the liposomal-based Lipofectamine 2000. With only a five-minute long transfection time we obtained at least 85 % transfected cells with 80 % maintained viability. Moreover, this protocol saves up to a day of experimental time since the cells are in suspension at the time of transfection, which allows for immediately re-plating into the appropriate format. This fast, simplified and highly efficient transfection method will be valuable for both basic research and high-throughput applications. PMID- 27358241 TI - Biotransformations of Bile Acids with Bacteria from Cayambe Slaughterhouse (Ecuador): Synthesis of Bendigoles. AB - The biotransformations of cholic acid (1a), deoxycholic acid (1b), and hyodeoxycholic acid (1c) to bendigoles and other metabolites with bacteria isolated from the rural slaughterhouse of Cayambe (Pichincha Province, Ecuador) were reported. The more active strains were characterized, and belong to the genera Pseudomonas and Rhodococcus. Various biotransformation products were obtained depending on bacteria and substrates. Cholic acid (1a) afforded the 3 oxo and 3-oxo-4-ene derivatives 2a and 3a (45% and 45%, resp.) with P. mendocina ECS10, 3,12-dioxo-4-ene derivative 4a (60%) with Rh. erythropolis ECS25, and 9,10 secosteroid 6 (15%) with Rh. erythropolis ECS12. Bendigole F (5a) was obtained in 20% with P. fragi ECS22. Deoxycholic acid (1b) gave 3-oxo derivative 2b with P. prosekii ECS1 and Rh. erythropolis ECS25 (20% and 61%, resp.), while 3-oxo-4-ene derivative 3b was obtained with P. prosekii ECS1 and P. mendocina ECS10 (22% and 95%, resp.). Moreover, P. fragi ECS9 afforded bendigole A (8b; 80%). Finally, P. mendocina ECS10 biotransformed hyodeoxycholic acid (1c) to 3-oxo derivative 2c (50%) and Rh. erythropolis ECS12 to 6alpha-hydroxy-3-oxo-23,24-dinor-5beta-cholan 22-oic acid (9c, 66%). Bendigole G (5c; 13%) with P. prosekii ECS1 and bendigole H (8c) with P. prosekii ECS1 and Rh. erythropolis ECS12 (20% and 16%, resp.) were obtained. PMID- 27358242 TI - Reframing the association and significance of co-morbidities in heart failure. AB - Several co-existing diseases and/or conditions (co-morbidities) are present in patients with heart failure (HF), with diverse clinical relevance. Multiple mechanisms may underlie the co-existence of HF and co-morbidities, including direct causation, associated risk factors, heterogeneity, and independence. The complex inter-relationship of co-morbidities and their impact on the cardiovascular system contribute to the features of HF, both with reduced (HFrEF) and preserved ejection fraction (HFpEF). The purpose of this work is to provide an overview of the contribution of major cardiac and non-cardiac co-morbidities to HF development and outcomes, in the context of both HFpEF and HFrEF. Accordingly, epidemiological evidence linking co-morbidities to HF and the effect of prevalent and incident co-morbidities on HF outcome will be reviewed. PMID- 27358243 TI - Letter to "Tardive intermittent massive vaginal bleeding from abnormal blood vessels within cesarean scar: Two more new cases should bring our attention to a new entity": Really, a new entity? PMID- 27358244 TI - Metastatic pancreatic adenocarcinoma associated with chronic calcific pancreatitis and a heterozygous SPINK1 N34S mutation. AB - Contrary to patients with a cationic trypsinogen gene (PRSS1) mutations, Serine protease inhibitor Kazal-type 1 (SPINK1) heterozygote gene mutation carriers have a very low penetrance for acute, acute recurrent and/or chronic pancreatitis. Despite this, heterozygote SPINK 1 gene mutation patients have a similar age of onset of pancreatitis as PRSS 1 gene mutation patients. While the substantially elevated risk of pancreatic cancer in patients with PRSS1 gene mutations with chronic pancreatitis has been well established, little is known about the risk of pancreatic cancer in SPINK 1 gene mutation carriers with pancreatitis. We describe a case of malignant pancreatic cancer diagnosed in a young patient with chronic pancreatitis who is a SPINK 1 heterozygote gene mutation carrier. The risk of pancreatic cancer in gene mutation patients with chronic pancreatitis, in addition to screening options and management options for these patients is discussed. PMID- 27358245 TI - Development of the Music Therapy Assessment Tool for Advanced Huntington's Disease: A Pilot Validation Study. AB - BACKGROUND: Case studies of people with Huntington's disease (HD) report that music therapy provides a range of benefits that may improve quality of life; however, no robust music therapy assessment tools exist for this population. OBJECTIVE: Develop and conduct preliminary psychometric testing of a music therapy assessment tool for patients with advanced HD. METHODS: First, we established content and face validity of the Music Therapy Assessment Tool for Advanced HD (MATA-HD) through focus groups and field testing. Second, we examined psychometric properties of the resulting MATA-HD in terms of its construct validity, internal consistency, and inter-rater and intra-rater reliability over 10 group music therapy sessions with 19 patients. RESULTS: The resulting MATA-HD included a total of 15 items across six subscales (Arousal/Attention, Physical Presentation, Communication, Musical, Cognition, and Psychological/Behavioral). We found good construct validity (r >= 0.7) for Mood, Communication Level, Communication Effectiveness, Choice, Social Behavior, Arousal, and Attention items. Cronbach's alpha of 0.825 indicated good internal consistency across 11 items with a common focus of engagement in therapy. The inter-rater reliability (IRR) Intra-Class Coefficient (ICC) scores averaged 0.65, and a mean intra-rater ICC reliability of 0.68 was obtained. Further training and retesting provided a mean of IRR ICC of 0.7. CONCLUSION: Preliminary data indicate that the MATA-HD is a promising tool for measuring patient responses to music therapy interventions across psychological, physical, social, and communication domains of functioning in patients with advanced HD. PMID- 27358246 TI - Real-World Multicenter Registry of Patients with Severe Coronary Artery Calcification Undergoing Orbital Atherectomy. AB - OBJECTIVES: We evaluated the safety and efficacy of orbital atherectomy in real world patients with severe coronary artery calcification (CAC). BACKGROUND: The presence of severe CAC increases the complexity of percutaneous coronary intervention as it may impede stent delivery and optimal stent expansion. Atherectomy may be an indispensable tool for uncrossable or undilatable lesions by modifying severe CAC. Although the ORBIT I and II trials report that orbital atherectomy was safe and effective for the treatment of severe CAC, patients with kidney disease, recent myocardial infarction, long diffuse disease, severe left ventricular dysfunction, and unprotected left main disease were excluded. METHODS: This retrospective study included 458 consecutive patients with severe CAC who underwent orbital atherectomy followed by stenting from October 2013 to December 2015 at 3 centers. RESULTS: The primary endpoint of major adverse cardiac and cerebrovascular events at 30 days was 1.7%. Low rates of 30-day all cause mortality (1.3%), myocardial infarction (1.1%), target vessel revascularization (0%), stroke (0.2%), and stent thrombosis (0.9%) were observed. Angiographic complications were low: perforation was 0.7%, dissection 0.9%, and no-reflow 0.7%. Emergency coronary artery bypass graft surgery was performed in 0.2% of patients. CONCLUSION: In the largest real-world study of patients who underwent orbital atherectomy, including high-risk patients who were not surgical candidates as well as those with very complex coronary anatomy, acute and short term adverse clinical event rates were low. A randomized clinical trial is needed to identify the ideal treatment strategy for patients with severe CAC. PMID- 27358247 TI - Applying orthodontic tooth extrusion in a patient treated with bisphosphonate and irradiation: a case report. AB - Bisphosphonates and irradiation are useful medical treatments, but can often cause oral complications such as medication-related oral necrosis of the jaw (MRONJ) and osteoradionecrosis (ORN) during oral surgery, including tooth extraction. Therefore, we should take all risks into consideration carefully before choosing dental treatment for patients with a medical history of such therapies. A 55-year-old woman who underwent cord blood transplantation to treat extranodal natural killer T (NK/T) cell lymphoma (nasal type IVB) had a medical history of bisphosphonate and irradiation treatments. We treated her residual tooth root by applying orthodontic extrusion to avoid extraction and successfully restored the tooth. Application of an orthodontic tooth extrusion technique for conservative treatment of a residual tooth is a useful means of avoiding MRONJ or ORN in patients who have a medical history of bisphosphonate and irradiation treatments. PMID- 27358248 TI - Functional trait differences influence neighbourhood interactions in a hyperdiverse Amazonian forest. AB - As distinct community assembly processes can produce similar community patterns, assessing the ecological mechanisms promoting coexistence in hyperdiverse rainforests remains a considerable challenge. We use spatially explicit neighbourhood models of tree growth to quantify how functional trait and phylogenetic similarities predict variation in growth and crowding effects for the 315 most abundant tree species in a 25-ha lowland rainforest plot in Ecuador. We find that functional trait differences reflect variation in (1) species maximum potential growth, (2) the intensity of interspecific interactions for some species, and (3) species sensitivity to neighbours. We find that neighbours influenced tree growth in 28% of the 315 focal tree species. Neighbourhood effects are not detected in the remaining 72%, which may reflect the low statistical power to model rare taxa and/or species insensitivity to neighbours. Our results highlight the spectrum of ways in which functional trait differences can shape community dynamics in highly diverse rainforests. PMID- 27358249 TI - A Titanium-Doped SiOx Passivation Layer for Greatly Enhanced Performance of a Hematite-Based Photoelectrochemical System. AB - This study introduces an in situ fabrication of nanoporous hematite with a Ti doped SiOx passivation layer for a high-performance water-splitting system. The nanoporous hematite with a Ti-doped SiOx layer (Ti-(SiOx /np-Fe2 O3 )) has a photocurrent density of 2.44 mA cm(-2) at 1.23 VRHE and 3.70 mA cm(-2) at 1.50 VRHE . When a cobalt phosphate co-catalyst was applied to Ti-(SiOx /np-Fe2 O3 ), the photocurrent density reached 3.19 mA cm(-2) at 1.23 VRHE with stability, which shows great potential of the use of the Ti-doped SiOx layer with a synergistic effect of decreased charge recombination, the increased number of active sites, and the reduced hole-diffusion pathway from the hematite to the electrolyte. PMID- 27358250 TI - Prohibit, constrain, encourage, or purchase: how should we engage with the private health-care sector? AB - The private for-profit sector's prominence in health-care delivery, and concern about its failures to deliver social benefit, has driven a search for interventions to improve the sector's functioning. We review evidence for the effectiveness and limitations of such private sector interventions in low-income and middle-income countries. Few robust assessments are available, but some conclusions are possible. Prohibiting the private sector is very unlikely to succeed, and regulatory approaches face persistent challenges in many low-income and middle-income countries. Attention is therefore turning to interventions that encourage private providers to improve quality and coverage (while advancing their financial interests) such as social marketing, social franchising, vouchers, and contracting. However, evidence about the effect on clinical quality, coverage, equity, and cost-effectiveness is inadequate. Other challenges concern scalability and scope, indicating the limitations of such interventions as a basis for universal health coverage, though interventions can address focused problems on a restricted scale. PMID- 27358251 TI - Performance of private sector health care: implications for universal health coverage. AB - Although the private sector is an important health-care provider in many low income and middle-income countries, its role in progress towards universal health coverage varies. Studies of the performance of the private sector have focused on three main dimensions: quality, equity of access, and efficiency. The characteristics of patients, the structures of both the public and private sectors, and the regulation of the sector influence the types of health services delivered, and outcomes. Combined with characteristics of private providers including their size, objectives, and technical competence-the interaction of these factors affects how the sector performs in different contexts. Changing the performance of the private sector will require interventions that target the sector as a whole, rather than individual providers alone. In particular, the performance of the private sector seems to be intrinsically linked to the structure and performance of the public sector, which suggests that deriving population benefit from the private health-care sector requires a regulatory response focused on the health-care sector as a whole. PMID- 27358252 TI - Managing the public-private mix to achieve universal health coverage. AB - The private sector has a large and growing role in health systems in low-income and middle-income countries. The goal of universal health coverage provides a renewed focus on taking a system perspective in designing policies to manage the private sector. This perspective requires choosing policies that will contribute to the performance of the system as a whole, rather than of any sector individually. Here we draw and extrapolate main messages from the papers in this Series and additional sources to inform policy and research agendas in the context of global and country level efforts to secure universal health coverage in low-income and middle-income countries. Recognising that private providers are highly heterogeneous in terms of their size, objectives, and quality, we explore the types of policy that might respond appropriately to the challenges and opportunities created by four stylised private provider types: the low-quality, underqualified sector that serves poor people in many countries; not-for-profit providers that operate on a range of scales; formally registered small-to-medium private practices; and the corporate commercial hospital sector, which is growing rapidly and about which little is known. PMID- 27358253 TI - What is the private sector? Understanding private provision in the health systems of low-income and middle-income countries. AB - Private health care in low-income and middle-income countries is very extensive and very heterogeneous, ranging from itinerant medicine sellers, through millions of independent practitioners-both unlicensed and licensed-to corporate hospital chains and large private insurers. Policies for universal health coverage (UHC) must address this complex private sector. However, no agreed measures exist to assess the scale and scope of the private health sector in these countries, and policy makers tasked with managing and regulating mixed health systems struggle to identify the key features of their private sectors. In this report, we propose a set of metrics, drawn from existing data that can form a starting point for policy makers to identify the structure and dynamics of private provision in their particular mixed health systems; that is, to identify the consequences of specific structures, the drivers of change, and levers available to improve efficiency and outcomes. The central message is that private sectors cannot be understood except within their context of mixed health systems since private and public sectors interact. We develop an illustrative and partial country typology, using the metrics and other country information, to illustrate how the scale and operation of the public sector can shape the private sector's structure and behaviour, and vice versa. PMID- 27358254 TI - The perils and possibilities of the private health sector. PMID- 27358256 TI - Anthony Costello: Irreverent, melancholic, dogged. PMID- 27358255 TI - Intrauterine anaesthetic after hysteroscopy to reduce post-operative pain - A double blind randomised controlled trial. AB - BACKGROUND: Pain after hysteroscopy is usually minimal but some women need additional analgesia while in the recovery ward and some require overnight hospital admission to control pain. Intrauterine installation of an anaesthetic after hysteroscopy may reduce pain. AIMS: To see if intrauterine levobupivacaine reduces post-procedure pain, need for analgesia and allow earlier return to normal activity. MATERIALS AND METHODS: This was a double-blind randomised controlled trial. Women having hysteroscopy under general anaesthesia were allocated to receive intrauterine instillation of levubupivacaine or normal saline at the end of the procedure. Women were assessed in the recovery ward by a verbal descriptor pain scale and need for additional analgesia and followed up on day 3 to further assess pain and return to normal activity. RESULTS: There were no significant differences in demographic characteristics or indication for surgery between the 224 women in the study group or the 214 women in the control group. At two hours post-procedure, 156/224 (70%) study women versus 119/214 (56%) control women had no pain; (relative risk (RR) 0.68 and 95% confidence interval (CI) 0.53-0.87). There were 182/224 (81%) study women versus 154/214 (72%) control women with a pain score < 5 (RR 0.67; 95% CI 0.47-0.95). Fewer women in the study group required additional analgesia 54/224 (24%) versus 88/214 (41%) (RR 0.58; 95% CI 0.44-0.78). There was no significant difference between groups with regards to pain at 24 h post-procedure or return to activity. CONCLUSION: Intrauterine instillation of levobupivacaine reduced post-procedure pain and need for additional pain relief. PMID- 27358257 TI - Long-Term Risk for Noncervical Anogenital Cancer in Women with Previously Diagnosed High-Grade Cervical Intraepithelial Neoplasia: A Danish Nationwide Cohort Study. AB - BACKGROUND: High-risk human papillomavirus (HPV) is essential for developing high grade cervical intraepithelial neoplasia (CIN2 and CIN3) and has also been associated with noncervical anogenital cancers. However, limited knowledge exists about the long-term risk for anal, vulvar, and vaginal cancer following CIN2 or CIN3 diagnosis. METHODS: In a nationwide cohort study, we followed nearly 2.8 million women born in 1918-1990 who were recorded as living in Denmark between January 1, 1978 and December 31, 2012. The cohort was linked to multiple nationwide registers to obtain information on cancer diagnoses and confounders. Follow-up started when the women reached 18 years, date of immigration, or January 1978, and continued until emigration, death, December 31, 2012, or the date of first diagnosis of anogenital or rectal cancer. RESULTS: Women with a history of CIN2 or CIN3 had higher risks for subsequent anal, vulvar, and vaginal cancer than women with no such history. The relative risks were higher for CIN3 than CIN2. No excess risk was found for rectal cancer. Analyses in which time since first CIN3 was taken into account showed increased relative risks for anal [HR = 4.8; 95% confidence interval (CI), 3.3-7.0], vulvar (HR = 3.2; 95% CI, 2.0 5.3), and vaginal (HR = 5.5; 95% CI, 2.4-12.3) cancers >=25 years after CIN3 diagnosis. CONCLUSION: Women with a history of CIN2 or CIN3 have a long-term increased relative risk for developing anal, vulvar, and vaginal cancer due to an impaired ability to control a persistent HPV infection. IMPACT: This finding adds to our understanding of the relation between HPV infection and noncervical anogenital cancer. Cancer Epidemiol Biomarkers Prev; 25(7); 1090-7. (c)2016 AACR. PMID- 27358258 TI - Particulate beta-glucans synergistically activate TLR4 and Dectin-1 in human dendritic cells. AB - SCOPE: The major receptor for beta(1-3)-glucans on immune cells is considered to be Dectin-1 receptor. Particulate beta-glucans induce stronger immune responses than soluble beta-glucans by clustering of Dectin-1 receptors. Here, it was hypothesized that activation of other pattern recognition receptors such as Toll like receptor 4 (TLR4) can also contribute to enhanced activity of immune cells after exposure to particulate beta-glucans. METHODS AND RESULTS: To test this hypothesis, reporter cell lines were designed expressing TLR4 with either Dectin 1A or Dectin-1B, that is, one of the two transcript variants of human Dectin-1 receptors. Enhanced NF-kappaB activation was observed after stimulation with particulate beta-glucans in both Dectin-1A-TLR4 and the Dectin-1B-TLR4 cell lines. This was different with soluble beta-glucans, which enhanced activation in Dectin-1A-TLR4 cell lines but not in Dectin-1B-TLR4 cells. The synergistic activation of TLR4 and Dectin-1 by particulate beta-glucans was confirmed in human dendritic cells. The effects of particulate beta-glucan induced TLR4 binding were regulatory as blocking TLR4 enhanced pro-inflammatory cytokine IL 23, IL-4, IL-6, and TNF-alpha production. CONCLUSION: These results suggest that TLR4 and Dectin-1 are synergistically activated by particulate beta-glucans, wherein TLR4 activates an immune regulatory pathway in human dendritic cells. Our data suggest that beta-glucan is an immune regulatory ligand for TLR4. PMID- 27358259 TI - Impacts of population growth, urbanisation and sanitation changes on global human Cryptosporidium emissions to surface water. AB - Cryptosporidium is a pathogenic protozoan parasite and is a leading cause of diarrhoea worldwide. The concentration of Cryptosporidium in the surface water is a determinant for probability of exposure and the risk of disease. Surface water concentrations are expected to change with population growth, urbanisation and changes in sanitation. The objective of this paper is to assess the importance of future changes in population, urbanisation and sanitation on global human emissions of Cryptosporidium to surface water. The GloWPa-Crypto H1 (the Global Waterborne Pathogen model for Human Cryptosporidium emissions version 1) model is presented and run for 2010 and with scenarios for 2050. The new scenarios are based on the Shared Socio-economic Pathways (SSPs) developed for the climate community. The scenarios comprise assumptions on sanitation changes in line with the storylines and population and urbanisation changes from the SSPs. In SSP1 population growth is limited, urbanisation large and sanitation and waste water treatment strongly improve. SSP1* is the same as SSP1, but waste water treatment does not improve. SSP3 sees large population growth, moderate urbanisation and sanitation and waste water treatment fractions that are the same as in 2010. Total global Cryptosporidium emissions to surface water for 2010 are estimated to be 1.6*1017 oocysts per year, with hotspots in the most urbanised parts of the world. In 2050 emissions are expected to decrease by 24% or increase by 52% and 70% for SSP1, SSP3 and SSP1* respectively. The emissions increase in all scenarios for countries in the Middle East and Africa (MAF) region, while emissions in large parts in Europe decrease in scenarios SSP1 and SSP3. Improving sanitation by connecting the population to sewers, should be combined with waste water treatment, otherwise (SSP1*) emissions in 2050 are expected to be much larger than in a situation with strong population growth and slow development of safe water and improved sanitation (SSP3). The results show that population increase, urbanisation and changes in sanitation should be considered when water quality and resulting health risks are estimated by water managers or public health specialists. PMID- 27358260 TI - Relationships Among Perceived Stress, Bullying, Cortisol, and Depressive Symptoms in Ninth-Grade Adolescents: A Pilot Study. AB - Adolescence is considered a critical period for risk of depressive symptoms, with prevalence ranging from 13% to 34%. Few studies have examined the relationships among perceived stress, bullying, and depressive symptoms accompanied by a biological marker of stress (cortisol). The purpose of this pilot study was to determine the feasibility of collecting biological specimens in a high school setting, including a morning and afternoon sample of salivary cortisol as well as computer-based survey data in order to examine the relationships among these variables in ninth-grade adolescents. A convenience sample of 31 ninth-grade students from a Southern suburban high school participated in this cross sectional, correlational study. Perceived stress contributed the most toward the variance in depressive symptoms ( F = 29.379, df = 1, p < .001, partial eta square [[Formula: see text]] = 0.583). Females ( n = 15) had higher depressive symptoms scores than males, n = 16; t(29) = -2.94, df = 29, p = .023. Bullying scores were low and not significantly correlated with depressive symptoms, but participants reported more verbal/relational bullying as compared to physical, cultural, or cyberbullying. Cortisol slopes were normal (a negative change) for 20 participants (64.5%), while 4 (12.9%) had a blunted cortisol slope (less than .01 MUg/dl change from morning to afternoon) and 7 (22.36%) had an opposite cortisol slope (morning low and afternoon high). Data collection procedures (salivary cortisol and computer-based surveys) were feasible in a school setting. High rates of perceived stress and depressive symptoms warrant a larger study in the future. PMID- 27358261 TI - A School-Based Intervention to Reduce Excess Weight in Overweight and Obese Primary School Students. AB - BACKGROUND: This study evaluated the effect of an intervention for reducing excess weight gain in primary school-age children in Tehran. METHODS: A cluster randomized controlled trial was conducted in 12 primary schools in Tehran. Three hundred thirty-four pupils, 167 in the intervention and 167 in the comparison group, determined to be overweight or obese based on World Health Organization standards, were recruited for the study. The intervention included nutrition education and increased physical activity (PA) for the pupils, lifestyle modification for parents, and a change in food items sold at the schools' canteens. The entire intervention lasted approximately 18 weeks. Measures were taken before and immediately after the intervention. RESULTS: The intervention significantly reduced body mass index Z-score and hip circumference (p = .003 and p < .001, respectively). Waist circumference increased in both groups, but the increase was higher in the comparison group (p = .001). No significant difference was seen in time spent on TV viewing between groups (p = .08). Vigorous PA increased in the intervention group (p < .001), while the comparison group showed an increase in moderate activity only (p < .001). Energy intake increased significantly in the intervention group (p < .001). Neither triceps skinfold thickness nor time spent on the computer changed in the intervention group (p = .51 and p = .1, respectively), while they increased in the comparison group (p < .001 and p = .004, respectively). CONCLUSION: The study provides a successful model for the implementation of similar interventions throughout the country. PMID- 27358262 TI - Opioid sparing effect and safety of nefopam in patient controlled analgesia after laparotomy: A randomized, double blind study. AB - OBJECTIVES: A double-blind randomised study to evaluate the opioid sparing effect and safety of nefopam when administered via intravenous patient controlled analgesia (PCA) with fentanyl. METHODS: Patients planned for elective open laparotomy, were randomly assigned to receive into fentanyl 25 ug/ml (SF group) or nefopam 2.4 mg/ml plus fentanyl 25 ug/ml (NF group). Patients were assessed before surgery and for 24 h postoperatively. RESULTS: Total PCA fentanyl consumption was significantly lower in the NF group (n = 35) than the SF group (n = 36). Pain scores were significantly lower and patients' satisfaction with treatment significantly better in the NF group than the SF group. Dry mouth and dizziness were significantly more frequent in the NF group than the SF group. There were no other statistically significant between-group differences in the incidence of adverse events. CONCLUSIONS: Intravenous PCA using nefopam + fentanyl following laparotomy has an opioid sparing effect and is associated with a low incidence of some of the typical opioid related adverse events. TRIAL REGISTRY: Clinicaltrials.gov Registration No: NCT02596269. PMID- 27358263 TI - People with low serum folate levels have higher risk of colorectal adenoma/advanced colorectal adenoma occurrence and recurrence in China. AB - OBJECTIVE: To investigate the potential association between serum folate levels and colorectal adenoma (CRA) occurrence and recurrence. METHODS: This prospective study measured baseline serum folate levels in outpatients who were screened for CRA using colonoscopy. Participants were then randomly selected to produce one group with CRA and one without CRA. These two subgroups underwent further follow up observations of colonoscopy to determine the occurrence of new and recurrent CRA. RESULTS: A total of 1310 participants were screened at baseline: 888 were healthy subjects without CRA; and 422 had CRA. Two subgroups were randomly selected (n = 200 per group) for follow-up. In the overall population, baseline serum folate levels were significantly lower in patients with CRA or advanced CRA (A-CRA) compared with healthy participants without CRA. Similar findings were shown for the follow-up study in terms of the association between CRA and A-CRA occurrence and recurrence and baseline serum folate levels. After controlling for confounders, increased serum folate was associated with a reduced risk of occurrence of CRA (odds ratio [OR] 0.993, 95% confidence interval [CI] 0.924, 1.066) and recurrence of CRA (OR 0.749, 95% CI 0.322, 1.742). CONCLUSIONS: Higher serum folate levels may be protective against CRA and/or A-CRA. PMID- 27358264 TI - Categorization and surgical management of posttraumatic midfoot malunion. AB - OBJECTIVE: To assess a classification system for midfoot injury that was based on the characteristics of the foot malunion and to evaluate the suggested treatment strategies. METHODS: This retrospective review of data from patients with posttraumatic midfoot malunion categorized each foot deformity into one of three types based on the foot arch and then separated these categories into one of three subtypes based on the forefoot deformity. According to the types of malunion, fascio-cutaneous flap, osteotomy, joint arthrodesis or realignment was used to correct the deformity. Patients were assessed before surgery and at 12 and 24 months postoperation. RESULTS: Of the 24 patients identified, six had Lisfranc joint injuries, nine had Lisfranc joint complex injuries combined with cuboid compression fractures and nine had Lisfranc joint complex injuries combined with navicular fractures. Overall, eight patients presented with poor soft tissue and massive scar at the dorsal foot. Visual analogue scale and American Orthopaedic Foot and Ankle Society midfoot scores significantly improved over the 24-month study period. At the end of the study, 21 of 24 patients (87.5%) rated their functional outcome as excellent or good. CONCLUSION: The classification of the midfoot malunion evaluated in this study may be helpful in the decision making process for surgical intervention. PMID- 27358265 TI - High Maternal Body Mass Index in Early Pregnancy and Risks of Stillbirth and Infant Mortality-A Population-Based Sibling Study in Sweden. AB - In a population-based case-control study, we investigated whether familial confounding influenced the associations between maternal overweight/obesity and risks of stillbirth and infant mortality by including both population and sister controls. Using nationwide data from the Swedish Medical Birth Register (1992 2011), we included all primiparous women with singleton births who also had a sister with a first birth during that time period. We used logistic regression analyses to calculate odds ratios (and 95% confidence intervals) adjusted for maternal age, height, smoking habits, education, and time period (5-year groups) of child's birth. Body mass index (BMI) was calculated as weight (kg)/height (m)(2) Compared with population controls with a normal BMI (18.5-24.9), stillbirth risk increased with increasing BMI (BMI 25-29.9: odds ratio (OR) = 1.51 (95% confidence interval (CI): 1.21, 1.89); BMI 30-34.9: OR = 1.77 (95% CI: 1.24, 2.50); BMI >=35: OR = 3.16 (95% CI: 2.10, 4.76)). The sister case-control analyses revealed similar results. Offspring of obese women (BMI >=30) had an increased risk of infant mortality when population controls were used (OR = 2.41, 95% CI: 1.83, 3.16), and an even higher risk was obtained when sister controls were used (OR = 4.04, 95% CI: 2.25, 7.25). We conclude that obesity in early pregnancy is associated with increased risks of stillbirth and infant mortality independently of genetic and early environmental risk factors shared within families. PMID- 27358267 TI - The Authors Reply. PMID- 27358266 TI - Conditions for Valid Empirical Estimates of Cancer Overdiagnosis in Randomized Trials and Population Studies. AB - Cancer overdiagnosis is frequently estimated using the excess incidence in a screened group relative to that in an unscreened group. However, conditions for unbiased estimation are poorly understood. We developed a mathematical framework to project the effects of screening on the incidence of relevant cancers-that is, cancers that would present clinically without screening. Screening advances the date of diagnosis for a fraction of preclinical relevant cancers. Which diagnoses are advanced and by how much depends on the preclinical detectable period, test sensitivity, and screening patterns. Using the model, we projected incidence in common trial designs and population settings and compared excess incidence with true overdiagnosis. In trials with no control arm screening, unbiased estimates are available using cumulative incidence if the screen arm stops screening and using annual incidence if the screen arm continues screening. In both designs, unbiased estimation requires waiting until screening stabilizes plus the maximum preclinical period. In continued-screen trials and population settings, excess cumulative incidence is persistently biased. We investigated this bias in published estimates from the European Randomized Study of Screening for Prostate Cancer after 9-13 years. In conclusion, no trial or population setting automatically permits unbiased estimation of overdiagnosis; sufficient follow-up and appropriate analysis remain crucial. PMID- 27358268 TI - Invited Commentary: Maternal Obesity and Impaired Fetal and Infant Survival-One More Piece Added to the Puzzle. AB - The association between maternal obesity and increased risks of stillbirth and infant mortality is well documented, but it has often been questioned whether the association is driven by obesity per se or by unmeasured factors such as insulin resistance or genes. In this issue of the Journal, Lindam et al. (Am J Epidemiol. 2016;184(2):98-105) present results from a sibling case-control study which strongly support that these tragic outcomes are independent of genetic and early environmental risk factors shared within families. By sampling sisters from the Swedish Medical Birth Register, Lindam et al. compared the body mass indices (weight (kg)/height (m)(2)) of women who had stillbirths and infant deaths with those of their sisters or of population controls. Significant excess risks of both outcomes were observed in obese women (body mass index >=30), and associations were strongest when sister controls were used. Although this careful analysis adds to the existing evidence of a causal relationship between maternal obesity and impaired fetal and infant survival, a biological pathway has not yet been established. Additionally, we are in urgent need of effective tools to reduce obesity in childbearing women and to identify and treat high-risk pregnancies. PMID- 27358269 TI - Re: "Asymptotically Unbiased Estimation of Exposure Odds Ratios in Complete Records Logistic Regression". PMID- 27358270 TI - UK science and health outside the EU. PMID- 27358271 TI - The title "therapy" and what do you do with it as a child? Recollections of being in child expressive arts group therapy. AB - The complexity of children's entrance into mental health treatment has been the growing focus of much recent research. However, little attention has been given to the exploration of this phenomenon from the clients' point of view. This study aimed to gain understanding of the experience of entering therapy as a child through examination of the recollections of adult former clients who had participated as children in expressive arts group therapy (EAGT). Semi-structured open-ended interviews were conducted with 20 adult former child therapy clients who had participated in EAGT for at least 1year. Two major themes were revealed: one concerning participants' perceptions of the reasons for being in therapy as children and the other concerning their recollections and perception of their attitudes toward the idea of being in therapy. These two themes point to the central role of social, emotional, and cognitive developmental factors in the establishment of attitudes toward enrollment in psychotherapy, highlighting the difference between adults and children. These findings correspond with other studies in this area, adding a presentation of the experience from the client's perspective. PMID- 27358273 TI - Urine sCD163: a window onto glomerular inflammation. PMID- 27358274 TI - Residual lifetime risk of chronic kidney disease. AB - Background: An accurate estimation of the lifetime risk of chronic kidney disease (CKD) can aid in patient education while also informing the development of public health screening programs and educational campaigns. Methods: Framingham Offspring Study participants were included if they were free of CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) at age 50 years and had at least two serum creatinine measures during follow-up (mean 16 years, 49 506 person years). We estimated the lifetime risk of CKD to age 90 years adjusting for the competing risk of death in the overall cohort and in population subgroups with known CKD risk factors including hypertension, obesity and diabetes. Results: Overall 3362 individuals (52% women) were included in the study. Mean age at study baseline was 54 years. By the end of the study, 729 individuals (21.7%) developed CKD and 618 (18.4%) died. At age 50 years, the cumulative lifetime risk of CKD was 41.3% [95% confidence interval (CI) 38.5-44.0]. The risk was increased in those with risk factors at baseline including diabetes (52.6%, 95% CI 44.8 60.4), hypertension (50.2%, 95% CI 46.1-54.3) and obesity (46.5%, 95% CI 41.1 52.0). For those individuals without any risk factors at baseline, the lifetime risk of CKD was lower (34.2%, 95% CI 29.4-39.0) relative to those with 1, 2 or 3 risk factors (45.0, 51.5 and 56.1% respectively, P < 0.01 for all compared with those with no risk factors). Conclusions: Four out of 10 individuals without CKD at age 50 years will eventually develop CKD. This risk is modified by the presence of hypertension, diabetes and obesity at baseline. This demonstrates the importance of early identification of CKD risk factors, to aid in patient education, and potentially to reduce the future risk of disease. PMID- 27358272 TI - Serum sodium and mortality in a national peritoneal dialysis cohort. AB - Background: Sodium disarrays are common in peritoneal dialysis (PD) patients, and may be associated with adverse outcomes in this population. However, few studies of limited sample size have examined the association of serum sodium with mortality in PD patients, with inconsistent results. We hypothesized that both hypo- and hypernatremia are associated with higher death risk in a nationally representative cohort of US PD patients. Methods: We sought to examine the association of serum sodium over time and mortality among 4687 adult incident PD patients from a large US dialysis organization who underwent one or more serum sodium measurements within the first 3 months of dialysis over January 2007 to December 2011. We examined the association of time-dependent and baseline sodium with all-cause mortality as a proxy of short- and long-term sodium-mortality associations, respectively. Hazard ratios were estimated using Cox models with three adjustment levels: minimally adjusted, case-mix adjusted, and case-mix + laboratory adjusted. Results: In time-dependent analyses, sodium levels <140 mEq/L were associated with incrementally higher death risk in case-mix models (ref: 140 to <142 mEq/L); following laboratory covariate adjustment, associations between lower sodium and higher mortality remained significant for levels <136 mEq/L. In analyses using baseline values, sodium levels <140 mEq/L were associated with higher mortality risk across all models (ref: 140 to <142 mEq/L). Conclusions: In PD patients, lower time-dependent and baseline sodium levels were independently associated with higher death risk. Further studies are needed to determine whether correction of dysnatremia improves longevity in this population. PMID- 27358275 TI - The locally activated renin-angiotensin system is involved in albumin permeability in glomerular endothelial cells under high glucose conditions. AB - Background: Although the diabetic milieu per se , hemodynamic changes, oxidative stress and local growth factors such as angiotensin II (AII) are considered to be mediators in the pathogenesis of diabetic nephropathy, the underlying pathways mediating the changes in glomerular endothelial cells (GECs) are not well understood. Therefore, we investigated changes in the renin-angiotensin system (RAS) components in high glucose (HG)-stimulated GECs and the role of the local RAS in morphological and functional changes in GECs under diabetic conditions. Methods: We stimulated GECs with 5.6 mM glucose or 30 mM glucose with or without an angiotensin II type I receptor blocker (ARB) in vitro and also performed experiments with Sprague-Dawley rats injected with diluent ( n = 16) or streptozotocin [ n = 16, diabetes (DM)]. Eight rats from each group were treated with ARB for 3 months in vivo . Real-time polymerase chain reaction, western blot analysis, enzyme-linked immunosorbent assay and immunofluorescent staining using cultured GECs were performed. The permeability of GECs to macromolecules was assessed by measuring the passage of fluorescein isothiocyanate-labeled bovine serum albumin. Morphological changes were also evaluated by scanning and transmission electron microscopy. Results: There were significant increases in angiotensinogen expression in HG-stimulated GECs along with significant increases in AI and AII levels. Moreover, the expression of heparan sulfate glycosaminoglycans (HS-GAG) assessed by immunofluorescent staining was significantly lower and the permeability to albumin was significantly higher in GECs exposed to HG medium, and ARB treatment significantly abrogated these changes. Upon electron microscopy examination, the mean size of the GEC fenestrae was significantly greater in HG-stimulated GECs and DM rats, and these increases were significantly ameliorated by ARB. Conclusions: The local RAS within GECs was activated under HG conditions, and this activation may be associated with both an alteration in GEC fenestration and a decrease in HS-GAG, resulting in the development of albuminuria in diabetic nephropathy. PMID- 27358276 TI - From cineradiography to biorobots: an approach for designing robots to emulate and study animal locomotion. AB - Robots are increasingly used as scientific tools to investigate animal locomotion. However, designing a robot that properly emulates the kinematic and dynamic properties of an animal is difficult because of the complexity of musculoskeletal systems and the limitations of current robotics technology. Here, we propose a design process that combines high-speed cineradiography, optimization, dynamic scaling, three-dimensional printing, high-end servomotors and a tailored dry-suit to construct Pleurobot: a salamander-like robot that closely mimics its biological counterpart, Pleurodeles waltl Our previous robots helped us test and confirm hypotheses on the interaction between the locomotor neuronal networks of the limbs and the spine to generate basic swimming and walking gaits. With Pleurobot, we demonstrate a design process that will enable studies of richer motor skills in salamanders. In particular, we are interested in how these richer motor skills can be obtained by extending our spinal cord models with the addition of more descending pathways and more detailed limb central pattern generator networks. Pleurobot is a dynamically scaled amphibious salamander robot with a large number of actuated degrees of freedom (DOFs: 27 in total). Because of our design process, the robot can capture most of the animal's DOFs and range of motion, especially at the limbs. We demonstrate the robot's abilities by imposing raw kinematic data, extracted from X-ray videos, to the robot's joints for basic locomotor behaviours in water and on land. The robot closely matches the behaviour of the animal in terms of relative forward speeds and lateral displacements. Ground reaction forces during walking also resemble those of the animal. Based on our results, we anticipate that future studies on richer motor skills in salamanders will highly benefit from Pleurobot's design. PMID- 27358277 TI - High turnover drives prolonged persistence of influenza in managed pig herds. AB - Pigs have long been hypothesized to play a central role in the emergence of novel human influenza A virus (IAV) strains, by serving as mixing vessels for mammalian and avian variants. However, the key issue of viral persistence in swine populations at different scales is ill understood. We address this gap using epidemiological models calibrated against seroprevalence data from Dutch finishing pigs to estimate the 'critical herd size' (CHS) for IAV persistence. We then examine the viral phylogenetic evidence for persistence by comparing human and swine IAV. Models suggest a CHS of approximately 3000 pigs above which influenza was likely to persist, i.e. orders of magnitude lower than persistence thresholds for IAV and other acute viruses in humans. At national and regional scales, we found much stronger empirical signatures of prolonged persistence of IAV in swine compared with human populations. These striking levels of persistence in small populations are driven by the high recruitment rate of susceptible piglets, and have significant implications for management of swine and for overall patterns of genetic diversity of IAV. PMID- 27358278 TI - Self-organization of chemoattractant waves in Dictyostelium depends on F-actin and cell-substrate adhesion. AB - In the social amoeba Dictyostelium discoideum, travelling waves of extracellular cyclic adenosine monophosphate (cAMP) self-organize in cell populations and direct aggregation of individual cells to form multicellular fruiting bodies. In contrast to the large body of studies that addressed how movement of cells is determined by spatial and temporal cues encoded in the dynamic cAMP gradients, how cell mechanics affect the formation of a self-generated chemoattractant field has received less attention. Here, we show, by live cell imaging analysis, that the periodicity of the synchronized cAMP waves increases in cells treated with the actin inhibitor latrunculin. Detail analysis of the extracellular cAMP induced transients of cytosolic cAMP (cAMP relay response) in well-isolated cells demonstrated that their amplitude and duration were markedly reduced in latrunculin-treated cells. Similarly, in cells strongly adhered to a poly-l lysine-coated surface, the response was suppressed, and the periodicity of the population-level oscillations was markedly lengthened. Our results suggest that cortical F-actin is dispensable for the basic low amplitude relay response but essential for its full amplification and that this enhanced response is necessary to establish high-frequency signalling centres. The observed F-actin dependence may prevent aggregation centres from establishing in microenvironments that are incompatible with cell migration. PMID- 27358280 TI - Medical research in India and the rise of non-communicable disease. PMID- 27358279 TI - The contribution of glycosaminoglycans to the mechanical behaviour of the posterior human sclera. AB - We characterized the structural and mechanical changes after experimental digestion of sulfated glycosaminoglycans (s-GAGs) in the human posterior sclera, using ultrasound thickness measurements and an inflation test with three dimensional digital image correlation (3D-DIC). Each scleral specimen was first incubated in a buffer solution to return to full hydration, inflation tested, treated in a buffer solution with chondroitinase ABC (ChABC), then inflation tested again. After each test series, the thickness of eight locations was measured. After enzymatic treatment, the average scleral thickness decreased by 13.3% (p < 0.001) and there was a stiffer overall stress-strain response (p < 0.05). The stress-strain response showed a statistically significant increase in the low-pressure stiffness, high-pressure stiffness and hysteresis. Thus, s-GAGs play a measurable role in the mechanical behaviour of the posterior human sclera. PMID- 27358281 TI - Impaired brainstem and thalamic high-frequency oscillatory EEG activity in migraine between attacks. AB - Introduction We investigated whether interictal thalamic dysfunction in migraine without aura (MO) patients is a primary determinant or the expression of its functional disconnection from proximal or distal areas along the somatosensory pathway. Methods Twenty MO patients and twenty healthy volunteers (HVs) underwent an electroencephalographic (EEG) recording during electrical stimulation of the median nerve at the wrist. We used the functional source separation algorithm to extract four functionally constrained nodes (brainstem, thalamus, primary sensory radial, and primary sensory motor tangential parietal sources) along the somatosensory pathway. Two digital filters (1-400 Hz and 450-750 Hz) were applied in order to extract low- (LFO) and high- frequency (HFO) oscillatory activity from the broadband signal. Results Compared to HVs, patients presented significantly lower brainstem (BS) and thalamic (Th) HFO activation bilaterally. No difference between the two cortical HFO as well as in LFO peak activations between the two groups was seen. The age of onset of the headache was positively correlated with HFO power in the right brainstem and thalamus. Conclusions This study provides evidence for complex dysfunction of brainstem and thalamocortical networks under the control of genetic factors that might act by modulating the severity of migraine phenotype. PMID- 27358282 TI - Presence of the hyperintense acute reperfusion marker on MRI after mechanical thrombectomy for large vessel occlusion is associated with worse early neurological recovery. AB - BACKGROUND: Mechanical thrombectomy has become the accepted treatment for large vessel occlusion in acute ischemic stroke. Unfortunately, a large cohort of patients do not achieve functional independence with treatment, even though the results are more robust than with medical management. The hyperintense acute reperfusion marker (HARM) on MRI is an indication of the breakdown of the blood brain barrier and reperfusion injury. OBJECTIVE: To examine the hypothesis that the presence of HARM on MRI correlates with worse neurological recovery after reperfusion therapy. METHODS: We retrospectively reviewed 35 consecutive patients who between February 24, 2016 and April 23, 2016 underwent MRI to determine the presence of HARM after thrombectomy for anterior circulation large vessel occlusion. Demographic, radiographic imaging, and outcome data were collected. Univariate and binary logistic regression models were performed to assess predictors for improvement of the National Institutes of Health Stroke Scale (NIHSS) score by >=8 points at 24 hours. RESULTS: The 35 patients studied had an average age of 64+/-14 years of age with a median NIHSS score of 15 (IQR 9-20). Eighteen patients (51%) were found to have a HARM-positive MRI. In univariate analysis, patients with HARM were older, had lower reperfusion rates and more postprocedural hemorrhages. In binary logistic regression modeling, the absence of HARM was independently associated with a >=8-point NIHSS score improvement at 24 hours (OR=7.14, 95% CI 1.22 to 41.67). CONCLUSIONS: This preliminary analysis shows that the presence of HARM may be linked to worse neurological recovery 24 hours after thrombectomy. Reperfusion injury may affect the number of patients achieving functional independence after treatment. PMID- 27358283 TI - Initiation Timing of Low-Intensity Pulsed Ultrasound Stimulation for Tendon-Bone Healing in a Rabbit Model. AB - BACKGROUND: Low-intensity pulsed ultrasound stimulation (LIPUS) has been proven to be a beneficial biophysical therapy for tendon-bone (T-B) healing. However, the optimal time to initiate LIPUS treatment has not been determined yet. LIPUS initiated at different stages of the inflammatory phase may profoundly affect T-B healing. PURPOSE: An established rabbit model was used to preliminarily investigate the effect of LIPUS initiation timing on T-B healing. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 112 mature rabbits that underwent partial patellectomy were randomly assigned to 4 groups: daily mock sonication (control group) and daily ultrasonication started immediately postoperatively (immediate group), on postoperative day 7 (7-day delayed group), or on postoperative day 14 (14-day delayed group). Peripheral leukocyte counts at the inflammatory phase were used to assess postoperative inflammation. The rabbits were sacrificed at 8 or 16 weeks postoperatively for microarchitectural, histological, and mechanical evaluations of the patella-patellar tendon (PPT) junction. RESULTS: The biomechanical properties of the PPT junction were significantly improved in the LIPUS-treated groups. Significantly higher ultimate strength and stiffness were seen in the 7-day delayed group compared with the other groups at 8 weeks postoperatively (P < .05 for all). Newly formed bone expansion from the remaining patella in the ultrasonic treatment groups was significantly increased and remodeled compared with the control group. Micro computed tomography analysis showed that the 7-day delayed group had significantly more bone volume and bone mineral content at the interface as compared with the other groups at 8 weeks postoperatively (P < .05 for all). Histologically, the ultrasonic treatment groups exhibited a significantly better PPT junction, as shown by more formation and remodeling of the fibrocartilage layer and newly formed bone. Additionally, peripheral leukocyte counts displayed a significant increase from postoperative day 1 to day 3 in the immediate group as compared with the other groups. Furthermore, postoperative hydrarthrosis was more likely in the immediate group. CONCLUSION: LIPUS started at postoperative day 7 had a more prominent effect on T-B healing compared with the other treatment regimens in this study. CLINICAL RELEVANCE: The findings of the study may help optimize the initiation timing of LIPUS for T-B healing. PMID- 27358284 TI - Fresh Osteochondral Allograft Versus Autograft: Twelve-Month Results in Isolated Canine Knee Defects. AB - BACKGROUND: Osteochondral autografts and allografts have been widely used in the treatment of isolated grade 4 articular cartilage lesions of the knee. However, there is a paucity of literature regarding the basic science investigating the direct comparison between fresh osteochondral allografts to autografts. HYPOTHESIS: At 12 months, fresh osteochondral allografts are equal to autografts with respect to function, bony incorporation into host bone, and chondrocyte viability. STUDY DESIGN: Controlled laboratory study. METHODS: Eight adult mongrel dogs underwent bilateral hindlimb osteochondral graft implantation in the knee after creation of an acute Outerbridge grade 4 cartilage defect. One hindlimb of each dog knee received an autograft, and the contralateral knee received an allograft. All dogs were sacrificed at 12 months. Graft analysis included gross examination, radiographs, magnetic resonance imaging (MRI), biomechanical testing, and histology. RESULTS: MRI demonstrated excellent bony incorporation of both autografts and allografts, except for 1 allograft that revealed partial incorporation. Histologic examination of cartilage showed intact hyaline appearance for both autografts and allografts, with fibrocartilage at the host-graft interface of both. Biomechanical testing demonstrated no significant difference between allografts and autografts (P = .76). Furthermore, no significant difference was observed between allografts and the native cartilage with biomechanical testing (P = .84). CONCLUSION: After 12 months from time of implantation, fresh osteochondral allograft tissue and autograft tissue in this study were not statistically different with respect to biomechanical properties, gross morphology, bony incorporation, or overall histologic characteristics. When compared with the previously reported 6-month incorporation rates, there was improved allograft and autograft incorporation at 12 months. CLINICAL RELEVANCE: With no significant differences in gross examination, radiographs, MRI, biomechanical testing, or histology in the canine model, the use of allograft tissue to treat osteochondral defects may eliminate the morbidity associated with autograft harvest. PMID- 27358285 TI - Muscle strengthening activity associates with reduced all-cause mortality in COPD. AB - Objective Emerging research suggests that aerobic-based physical activity may help to promote survival among chronic obstructive pulmonary disease patients. However, the extent to which engagement in resistance training on survival among chronic obstructive pulmonary disease patients is relatively unknown. Therefore, the purpose of this study was to examine the independent associations of muscle strengthening activities on all-cause mortality among a national sample of U.S. adults with chronic obstructive pulmonary disease. We hypothesize that muscle strengthening activities will be inversely associated with all-cause mortality. Methods Data from the 2003-2006 NHANES were employed, with follow-up through 2011. Aerobic-based physical activity was objectively measured via accelerometry, muscle strengthening activities engagement was assessed via self-report, and chronic obstructive pulmonary disease was assessed via physician-diagnosis. Results Analysis included 385 adults (20 + yrs) with chronic obstructive pulmonary disease, who represent 13.3 million chronic obstructive pulmonary disease patients in the USA. The median follow-up period was 78 months (IQR=64 90), with 82 chronic obstructive pulmonary disease patients dying during this period. For a two muscle strengthening activity sessions/week increase (consistent with national guidelines), chronic obstructive pulmonary disease patients had a 29% reduced risk of all-cause mortality (HR=0.71; 95% CI: 0.51 0.99; P = 0.04). Conclusion Participation in muscle strengthening activities, independent of aerobic-based physical activity and other potential confounders, is associated with greater survival among chronic obstructive pulmonary disease patients. PMID- 27358286 TI - The lived experience of having a rare medical disorder: Hermansky-Pudlak syndrome. AB - Hermansky-Pudlak Syndrome is a rare form of albinism, affecting approximately one in 500,000 to one in 1,000,000 non-Hispanic individuals. The syndrome is more commonly found in Hispanics, where one in 18,00 individuals in Northwestern Puerto Rico are impacted. Because of the rarity of this chronic condition, patients often face challenges in their ability to cope with the diagnosis. A phenomenological study was conducted to explore the experience of individuals with this rare genetic disease. A purposive sample of adults between the ages of 20 and 49 diagnosed with Hermansky-Pudlak Syndrome was interviewed (N = 23). The majority (83%) were female. Data analysis resulted in the emergence of themes related to long road to diagnosis, learning to move forward, burden of being the expert, and survival through belonging to the HPS community. PMID- 27358287 TI - Toxoplasmosis in female high school students, pregnant women and ruminants in Cyprus. AB - BACKGROUND: The protozoan parasite Toxoplasma gondii is important to human and animal health worldwide. This is the first study of prevalence of infection with T. gondii and associated risk factors in human populations and small ruminants in Cyprus. METHODS: A random sample of 18 schools out of 46 participated: 1056 girls aged 16 to 18 years completed a questionnaire and were serologically tested for Toxoplasma between 2008 and 2011 (response rate 30%). In addition, infection with T. gondii laboratory results of 23 076 pregnant women tested between 2009 and 2014 were obtained from hospital records. Finally, 163 (out of 3123) farms were randomly sampled and blood samples from 515 sheep and 581 goats were obtained. RESULTS: Estimated seropositivity prevalence in female students was 6.5% (95% CI 4.3 to 8.7%) and 18% (95% CI 17 to 19%) in pregnant women. Overall, 40.1% of the ruminants tested were seropositive (95% CI 37.2% to 43.0%). Seropositivity differed according to geographical region in all three groups. CONCLUSIONS: Further studies are needed to investigate the differences between regions that lead to differing prevalence levels and patterns between ruminants and humans so that health education policies can be developed to help prevent infection and reduce environmental contamination. PMID- 27358288 TI - Faecal contamination of commuters' hands in main vehicle stations in Dhaka city, Bangladesh. AB - BACKGROUND: Faecal-oral carriage via hands is an important transmission pathway for diarrhoeal pathogens. The level of faecal contamination of commuters' hands in Dhaka, Bangladesh, was examined in this study. METHODS: A total of 900 hand washing samples, including both left and right hands, were collected during one year to cover three different seasons in Bangladesh: winter, summer and rainy seasons. Standard membrane filtration technique was used to quantify total coliforms (TC), faecal coliforms (FC), faecal streptococci (FS), Escherichia coli (EC) and Clostridium perfringens (CP). RESULTS: The hands of the commuters were contaminated with TC, FC, FS, CP and EC. The TC, FC, FS, CP and EC counts were 1.95, 1.65, 4.04, 1.54 and1.46 log10 colony forming units (cfu) in the left hand; and 2.13, 1.82, 4.11, 1.52 and 1.61 log10 cfu in the right hand, respectively. There were no statistically significant differences in counts of left and right hands. The highest counts were observed for FS in all seasons. CONCLUSIONS: This evidence based study may be used to provide interventions to reduce the contamination of commuters' hands through washing with detergent and, thus, help to prevent the spread of infectious diseases. PMID- 27358289 TI - Exogenous application of abscisic acid (ABA) increases root and cell hydraulic conductivity and abundance of some aquaporin isoforms in the ABA-deficient barley mutant Az34. AB - BACKGROUND AND AIMS: Regulation of water channel aquaporins (AQPs) provides another mechanism by which abscisic acid (ABA) may influence water flow through plants. To the best of our knowledge, no studies have addressed the changes in ABA levels, the abundance of AQPs and root cell hydraulic conductivity (LpCell) in the same tissues. Thus, we followed the mechanisms by which ABA affects root hydraulics in an ABA-deficient barley mutant Az34 and its parental line 'Steptoe'. We compared the abundance of AQPs and ABA in cells to determine spatial correlations between AQP abundance and local ABA concentrations in different root tissues. In addition, abundance of AQPs and ABA in cortex cells was related to LpCell. METHODS: Root hydraulic conductivity (LpRoot) was measured by means of root exudation analyses and LpCell using a cell pressure probe. The abundance of ABA and AQPs in root tissues was assessed through immunohistochemical analyses. Isoform-specific antibodies raised against HvPIP2;1, HvPIP2;2 and HvPIP2;5 were used. KEY RESULTS: Immunolocalization revealed lower ABA levels in root tissues of Az34 compared with 'Steptoe'. Root hydraulic conductivity (LpRoot) was lower in Az34, yet the abundance of HvPIPs in root tissues was similar in the two genotypes. Root hair formation occurred closer to the tip, while the length of the root hair zone was shorter in Az34 than in 'Steptoe'. Application of external ABA to the root medium of Az34 and 'Steptoe' increased the immunostaining of root cells for ABA and for HvPIP2;1 and HvPIP2;2 especially in root epidermal cells and the cortical cell layer located beneath, parallel to an increase in LpRoot and LpCell Treatment of roots with Fenton reagent, which inhibits AQP activity, prevented the ABA-induced increase in root hydraulic conductivity. CONCLUSION: Shortly after (<2 h) ABA application to the roots of ABA-deficient barley, increased tissue ABA concentrations and AQP abundance (especially the plasma-membrane localized isoforms HvPIP2;1 and HvPIP2;2) were spatially correlated in root epidermal cells and the cortical cell layer located beneath, in conjunction with increased LpCell of the cortical cells. In contrast, long-term ABA deficiency throughout seedling development affects root hydraulics through other mechanisms, in particular the developmental timing of the formation of root hairs closer to the root tip and the length of the root hair zone. PMID- 27358290 TI - Longitudinal zonation pattern in Arabidopsis root tip defined by a multiple structural change algorithm. AB - BACKGROUND AND AIMS: The Arabidopsis thaliana root is a key experimental system in developmental biology. Despite its importance, we are still lacking an objective and broadly applicable approach for identification of number and position of developmental domains or zones along the longitudinal axis of the root apex or boundaries between them, which is essential for understanding the mechanisms underlying cell proliferation, elongation and differentiation dynamics during root development. METHODS: We used a statistics approach, the multiple structural change algorithm (MSC), for estimating the number and position of developmental transitions in the growing portion of the root apex. Once the positions of the transitions between domains and zones were determined, linear models were used to estimate the critical size of dividing cells (LcritD) and other parameters. KEY RESULTS: The MSC approach enabled identification of three discrete regions in the growing parts of the root that correspond to the proliferation domain (PD), the transition domain (TD) and the elongation zone (EZ). Simultaneous application of the MSC approach and G2-to-M transition (CycB1;1DB:GFP) and endoreduplication (pCCS52A1:GUS) molecular markers confirmed the presence and position of the TD. We also found that the MADS-box gene XAANTAL1 (XAL1) is required for the wild-type (wt) PD increase in length during the first 2 weeks of growth. Contrary to wt, in the xal1 loss-of-function mutant the increase and acceleration of root growth were not detected. We also found alterations in LcritD in xal1 compared with wt, which was associated with longer cell cycle duration in the mutant.Conclusions The MSC approach is a useful, objective and versatile tool for identification of the PD, TD and EZ and boundaries between them in the root apices and can be used for the phenotyping of different genetic backgrounds, experimental treatments or developmental changes within a genotype. The tool is publicly available at www.ibiologia.com.mx/MSC_analysis. PMID- 27358291 TI - Amphibians with infectious disease increase their reproductive effort: evidence for the terminal investment hypothesis. AB - Mounting an immune response to fight disease is costly for an organism and can reduce investment in another life-history trait, such as reproduction. The terminal investment hypothesis predicts that an organism will increase reproductive effort when threatened by disease. The reproductive fitness of amphibians infected with the deadly fungal pathogen Batrachochytrium dendrobatidis (Bd) is largely unknown. In this study, we explored gametogenesis in two endangered and susceptible frog species, Pseudophryne corroboree and Litoria verreauxii alpina. Gametogenesis, both oogenesis and spermatogenesis, increased when animals were experimentally infected with Bd In P. corroboree, infected males have thicker germinal epithelium, and a larger proportion of spermatocytes. In L. v. alpina, infected males had more spermatic cell bundles in total, and a larger proportion of spermatozoa bundles. In female L. v. alpina, ovaries and oviducts were larger in infected animals, and there were more cells present within the ovaries. Terminal investment has consequences for the evolution of disease resistance in declining species. If infected animals are increasing reproductive efforts and producing more offspring before succumbing to disease, it is possible that population-level selection for disease resistance will be minimized. PMID- 27358292 TI - Identification of ubiquinol cytochrome c reductase hinge (UQCRH) as a potential diagnostic biomarker for lung adenocarcinoma. AB - Ubiquinol cytochrome c reductase hinge (UQCRH) is a novel protein that localizes in the mitochondrial membrane and induces mitochondrial reactive oxygen species (ROS) generation. It had a high expression rate of 87.10% (108/124) in lung adenocarcinoma. Moreover, serum UQCRH level in patients with lung adenocarcinoma was significantly increased compared with that of pneumonia patients (p < 0.0001) and normal control subjects (p < 0.0001). Receiver operating characteristic curve analysis using an optimal cut-off value of 162.65 pg ml(-1) revealed sensitivity and specificity for the diagnosis of lung adenocarcinoma of 88.7% and 85.7%, respectively, with an area under the curve of 0.927 (95% CI: 0.892 to 0.962, p < 0.0001). Serum UQCRH discriminates lung adenocarcinoma patients from the population without cancer with considerable sensitivity and specificity, but it does not distinguish between heavy smokers and lung adenocarcinoma patients. Serum UQCRH could be a potential diagnostic biomarker for lung adenocarcinoma. PMID- 27358294 TI - TREXMO: A Translation Tool to Support the Use of Regulatory Occupational Exposure Models. AB - Occupational exposure models vary significantly in their complexity, purpose, and the level of expertise required from the user. Different parameters in the same model may lead to different exposure estimates for the same exposure situation. This paper presents a tool developed to deal with this concern-TREXMO or TRanslation of EXposure MOdels. TREXMO integrates six commonly used occupational exposure models, namely, ART v.1.5, STOFFENMANAGER((r)) v.5.1, ECETOC TRA v.3, MEASE v.1.02.01, EMKG-EXPO-TOOL, and EASE v.2.0. By enabling a semi-automatic translation between the parameters of these six models, TREXMO facilitates their simultaneous use. For a given exposure situation, defined by a set of parameters in one of the models, TREXMO provides the user with the most appropriate parameters to use in the other exposure models. Results showed that, once an exposure situation and parameters were set in ART, TREXMO reduced the number of possible outcomes in the other models by 1-4 orders of magnitude. The tool should manage to reduce the uncertain entry or selection of parameters in the six models, improve between-user reliability, and reduce the time required for running several models for a given exposure situation. In addition to these advantages, registrants of chemicals and authorities should benefit from more reliable exposure estimates for the risk characterization of dangerous chemicals under Regulation, Evaluation, Authorisation and restriction of CHemicals (REACH). PMID- 27358293 TI - Crystal structures of heterotypic nucleosomes containing histones H2A.Z and H2A. AB - H2A.Z is incorporated into nucleosomes located around transcription start sites and functions as an epigenetic regulator for the transcription of certain genes. During transcriptional regulation, the heterotypic H2A.Z/H2A nucleosome containing one each of H2A.Z and H2A is formed. However, previous homotypic H2A.Z nucleosome structures suggested that the L1 loop region of H2A.Z would sterically clash with the corresponding region of canonical H2A in the heterotypic nucleosome. To resolve this issue, we determined the crystal structures of heterotypic H2A.Z/H2A nucleosomes. In the H2A.Z/H2A nucleosome structure, the H2A.Z L1 loop structure was drastically altered without any structural changes of the canonical H2A L1 loop, thus avoiding the steric clash. Unexpectedly, the heterotypic H2A.Z/H2A nucleosome is more stable than the homotypic H2A.Z nucleosome. These data suggested that the flexible character of the H2A.Z L1 loop plays an essential role in forming the stable heterotypic H2A.Z/H2A nucleosome. PMID- 27358295 TI - Robert L. Replogle (1931-2016). PMID- 27358296 TI - Mortality Following Congenital Heart Surgery in Adults Can Be Predicted Accurately by Combining Expert-Based and Evidence-Based Pediatric Risk Scores. AB - OBJECTIVES: Currently, there are few specific risk stratification models available to predict mortality following congenital heart surgery in adults. We sought to evaluate whether the predictive power of the common pediatric scores is applicable for adults. In addition, we evaluated a new grown-ups with congenital heart disease (GUCH) score specifically designed for adults undergoing congenital heart surgery. METHODS AND RESULTS: Data of all consecutive patients aged 18 years or more, who underwent surgery for congenital heart disease (CHD) between 2004 and 2013 at our institution, were collected. We evaluated the Aristotle Basic Complexity (ABC), the Aristotle Comprehensive Complexity (ACC), the Risk Adjustment in Congenital Heart Surgery (RACHS-1), and the Society of Thoracic Surgeons (STS)-European Association for Cardiothoracic Surgery (EACTS) scores. The proposed GUCH score consists of the STS-EACTS score, the procedure-dependent and -independent factors of the ACC score, and age. The discriminatory power of the scores was assessed using the area under the receiver-operating characteristics curve (c-index). A total of 830 operations were evaluated. Hospital mortality was 2.9%. C-indexes were 0.67, 0.80, 0.62, 0.78, and 0.84 for the ABC, ACC, RACHS-1, STS-EACTS, and GUCH mortality scores, respectively. CONCLUSION: The evidence-based EACTS-STS score outperforms the expert-based ABC score. The expert-based ACC score is superior to the evidence-based EACTS-STS score since comorbidities are considered. Our proposed GUCH score outperforms all other scores since it integrates the advantages of the evidence-based EACTS-STS score for procedures and the expert-based ACC score for comorbidities. Evidence based scores for adults with CHD should include comorbidities and patient ages. PMID- 27358297 TI - Congenital Heart Surgery in Adults: The Challenge of Estimation of Risk of Mortality. PMID- 27358298 TI - Clinicians' Adherence to Guidelines on Evaluation of Hypertension in Children and Adolescents. AB - BACKGROUND: Hypertension is increasingly prevalent among children. We sought to review provider adherence to the National High Blood Pressure Education Program (NHBPEP) recommendations at a single academic medical center. METHODS: We identified children 3-18 years of age with hypertension based on outpatient visit International Classification of Diseases, Ninth Edition, Clinical Modification codes from 2006 to 2012. We calculated the odds of individual tests administration for ten recommended tests, adjusting for demographic characteristics. RESULTS: We identified 3,588 (1.7%) of 216,855 children diagnosed with hypertension at a median age of 14 years (25th and 75th percentile 10 and 16, respectively). No child received all ten recommended tests. The median number of tests administered was 2 (1, 4) but varied significantly by race and age. Urine drug screen (<1%) and renin levels (1%) were the least common, whereas serum creatinine (49%) and echocardiogram (40%) were the most common tests. Male children were more likely to receive an echocardiogram (odds ratio 1.43; 95% confidence interval: 1.24-1.64), and black children and those >=11 years old were less likely to have their serum creatinine checked. Adherence to the guidelines did not improve over time (P = .24). CONCLUSION: Children evaluated for hypertension in the outpatient setting infrequently receive the diagnostic tests recommended in the NHBPEP's report. Test administration frequency varies by patient demographics but has not improved significantly over time. PMID- 27358299 TI - Comparison of Feeding Strategies for Infants With Hypoplastic Left Heart Syndrome: A Randomized Controlled Trial. AB - INTRODUCTION: Infants with hypoplastic left heart syndrome are at risk for growth failure, particularly after stage 1 procedures. The effect of continuous enteral feedings on weight gain has not been previously investigated. METHODS: A randomized controlled trial was performed in infants with hypoplastic left heart syndrome and single ventricle variants after stage 1 procedures. Eligible infants were randomized to a continuous and intermittent feeding regimen or an exclusive intermittent feeding regimen after stage 1 procedures and continued until hospital discharge. Anthropometric measures and markers of nutritional status were assessed throughout hospitalization. RESULTS: Twenty-six infants completed the study. There were no significant differences in weight gain, growth, or nutritional status. Weight gain on full enteral feedings was 24.3 versus 23.6 g/d (P = .88) for the combination (continuous and intermittent) versus intermittent feeding groups. Weight-for-age Z scores at discharge were -1.37 versus -1.2 (P = .59) for the combination versus intermittent groups. CONCLUSIONS: No significant differences in weight gain, growth, or nutritional status were observed at hospital discharge between the two feeding strategies. Despite both groups achieving target daily weight gain after attaining full feeds, growth failure continued to be a problem after stage 1 procedures. Further strategies to improve growth during initial hospitalization are needed. PMID- 27358300 TI - Unscheduled Pediatric Intensive Care Unit Admissions in Patients With Cardiovascular Disease: Clinical Features and Outcomes. AB - BACKGROUND: An unscheduled readmission to the intensive care unit (ICU) is associated with increased morbidity and mortality in children. There is a paucity of data examining the impact of unscheduled admissions on outcomes in children with specific disease processes such as cardiovascular disease. We investigated the impact of scheduled versus unscheduled ICU admission on clinical outcomes and differences in patient characteristics in children with cardiovascular disease. METHODS: This was a retrospective analysis of contemporaneously collected clinical data using the Virtual PICU Systems database. All consecutive admissions at 102 participating pediatric ICUs in patients with cardiovascular disease were collected from October 2010 to September 2012. RESULTS: There were 48,653 admissions included in the analysis (44% scheduled and 56% unscheduled). The median patient age was 31 months. Unscheduled admissions were associated with longer ICU length of stay and increased mortality (both P < .001). Adjusting for age, weight, and primary ICU admission diagnosis (cardiovascular vs noncardiovascular), patients with unscheduled admissions had an increased odds of mortality (odds ratio = 4.8, P < .001). CONCLUSIONS: Unscheduled ICU admissions were associated with worse clinical outcomes including increased mortality. Efforts targeted at reducing unscheduled admissions in at-risk patients are warranted. PMID- 27358301 TI - Acute Kidney Injury Following Cardiac Surgery in Neonates and Young Infants: Experience of a Single Center Using Novel Perioperative Strategies. AB - OBJECTIVE: Acute kidney injury (AKI) following cardiac surgery is a serious complication with a reported incidence of 30% to 50%. This study sought to determine the prevalence and risk factors for AKI among neonates and young infants undergoing repair of cardiac defects at an institution using novel perioperative strategies. METHODS: A retrospective analysis of 102 consecutive infants (<2 months) undergoing repair of cardiac defects on cardiopulmonary bypass formed the study group. Cardiac diagnoses were stratified according to the Society of Thoracic Surgeons Congenital Heart Surgery (STAT) mortality categories. The prevalence of AKI within 72 hours was defined according to the three-stage Acute Kidney Injury Network criteria. Novel bypass strategies to preserve renal function included maintenance of higher hematocrit and high flow rates on cardiopulmonary bypass despite systemic hypothermia, and avoidance of albumin and milrinone in the perioperative period. RESULTS: Mean age was 24 +/- 19 days. Eighteen patients were less than 7 days of age at the time of surgery. Patient distribution according to STAT categories was as follows: 1 (n = 21), 2 (n = 12), 3 (n = 22), 4 (n = 28), and 5 (n = 19). The incidence of stages 1, 2, and 3 AKI in the population was 8% (n = 9), 2% (n = 2), and 0% (n = 0), respectively. On multivariate analysis higher STAT category was the only significant risk factor for AKI. CONCLUSION: Current incidence of AKI following cardiac surgery in young infants at our institution is low. Novel perioperative strategies may have contributed to the low observed incidence of AKI in our patient population. Increased complexity of heart disease was a risk factor for AKI. PMID- 27358302 TI - Three-Dimensional Reconstruction of Intracardiac Anatomy Using CTA and Surgical Planning for Double Outlet Right Ventricle: Early Experience at a Tertiary Care Congenital Heart Center. AB - BACKGROUND: Although transthoracic echocardiography (TTE) routinely establishes the diagnosis of double outlet right ventricle (DORV), it can be suboptimal for depicting exact ventricular septal defect (VSD) position, especially with respect to the outflow tracts. Advanced imaging with computed tomography angiography (CTA) can help visualize structures and relationships not easily seen by echo. Using computer-aided design, we have the ability to create three-dimensional (3D) models of the intracardiac anatomy, which can be helpful for better depicting the overall anatomy to assist surgical planning. METHODS: Patients with a diagnosis of DORV were retrospectively reviewed at our institution from October 2013 to April 2015. Patients who preoperatively underwent both TTE and CTA with 3D reconstruction of the intracardiac anatomy were included. Computed tomography angiography findings with 3D intracardiac model creation were compared to the surgical findings. RESULTS: Twenty-five patients underwent surgical repair of DORV during the study period. Five patients had CTA with 3D reconstruction, in addition to the standard TTE images, and were included in the study. In all five cases, CTA with 3D reconstruction of the intracardiac anatomy accurately depicted the VSD position relative to important adjacent structures, including the outflow tracts. CONCLUSION: Three-dimensional reconstruction of the intracardiac anatomy using CTA data can provide accurate data for presurgical planning of DORV repair and has the potential for being especially useful in patients for whom intracardiac anatomy and VSD position cannot be well seen by TTE. A larger prospective analysis is warranted to help validate this approach. PMID- 27358303 TI - Pulmonary Valve Replacement With Small Intestine Submucosa-Extracellular Matrix in a Porcine Model. AB - BACKGROUND: Prosthetic materials available for pediatric pulmonary valve replacement (PVR) lack growth potential, inevitably leading to a size mismatch. Small intestine submucosa-derived extracellular matrix (SIS-ECM) has been suggested to possess regenerative properties. We aimed to investigate its function and potential to increase in size as a PVR in a piglet. METHODS: An SIS ECM trileaflet valved conduit was designed. Hanford minipigs, n = 6 (10-34 kg), underwent PVR with an intended survival of six months, with monthly echocardiograms evaluating valve size and function. The conduit was excised for histologic analysis. RESULTS: Of the six, one was sacrificed at three months for midterm analysis, and one at month 3 due to endocarditis. The remaining four constituted the study cohort. The piglet weight increased by 186% (19.56 +/- 10.22 kg to 56.00 +/- 7.87 kg). Conduit size increased by 30% (1.42 +/- 0.14 cm to 1.84 +/- 0.14 cm; P < .01). The native right ventricular outflow tract increased by 43% and the native pulmonary artery by 84%, resulting in a peak gradient increase from 10.08 +/- 2.47 mm Hg to 36.25 +/- 18.80 mm Hg (P = .03). Additionally, all valves developed at least moderate regurgitation. Conduit histology showed advanced remodeling with myofibroblast infiltration, neovascularization, and endothelialization. The leaflets remodeled beginning at the base with the leaflet edge being less cellular. In addition to the known endocarditis, bacterial colonies were discovered within a leaflet in another. CONCLUSIONS: The SIS-ECM valved conduit implanted into a piglet demonstrated cellular infiltration with vascular remodeling and an increase in diameter. Conduit stenosis was a result of slower rates of size increase than native tissue. Suboptimal leaflet performance requires design modifications. PMID- 27358304 TI - Anteroposterior Pulmonary Venous Anatomy: A Hitherto Undescribed Pulmonary Venous Arrangement With Implication for the Senning Operation and a Proposed Method of Dealing With It. AB - We have encountered a hitherto undescribed anatomical variant of pulmonary vein anatomy in hearts with d-transposition or congenitally corrected transposition of the great arteries. In this variant, the inferior right pulmonary vein lies posterior rather than inferior to the superior right pulmonary vein. This variant of pulmonary vein anatomy may predispose to the development of pulmonary venous pathway obstruction following a Senning operation, since it is difficult to open the pulmonary veins in a way that ensures a wide-open pulmonary venous pathway to the atrioventricular valve of the systemic ventricle. A method of neutralizing this effect is described, with medium-term results. PMID- 27358305 TI - A Right Upper Lobe Mass in the Thorax After Modified Blalock-Taussig Shunt. AB - We report an incidental finding of pseudoaneurysm in a 10-month-old boy with tetralogy of Fallot and Down syndrome who had undergone placement of a modified Blalock-Taussig shunt at age four months. Computed tomography was a determinant exam for better assessment. The lesion was successfully resected with concomitant complete repair of tetralogy of Fallot in a single-stage. The child was asymptomatic at fourth month follow-up. PMID- 27358306 TI - Pentalogy of Cantrell: A View From Fetus to Operation With Multimodality Imaging. AB - Pentalogy of Cantrell and its surgical management have been previously described in the literature. To our knowledge, our case report is the first that is able to demonstrate the full use of multimodality imaging to describe it. Viewing this rare defect chronologically from fetal echocardiography, postnatal ultrasonography, and magnetic resonance imaging, as well as intraoperatively aided in the management of this patient. PMID- 27358307 TI - Takotsubo Syndrome in a Patient With a Previously Repaired Tetralogy of Fallot. PMID- 27358308 TI - Takotsubo Cardiomyopathy in an Adult Woman With Repaired Tetralogy of Fallot. PMID- 27358309 TI - Changes in movement symmetry over the stages of the shoeing process in military working horses. AB - Military working horses perform a high proportion of work on road surfaces and are shod frequently to deal with high attrition rates. The authors investigate the influence of shoeing on movement symmetry as an indirect indicator of mechanical differences affecting force production between contralateral limbs. In this quantitative observational study, inertial sensor gait analysis was performed in 23 Irish sport type horses (4-21 years, 1.58-1.85 m) in full ceremonial work at the King's Troop, Royal Horse Artillery. Changes in two movement symmetry measures (SI: symmetry index; MinDiff: difference between displacement minima) for head and pelvic movement were assessed at four stages of routine shoeing: 'old shoes', 'shoes removed', 'trimmed', 'reshod'. Horses were assessed applying shoes to the front limbs (N=10), to the hindlimbs (N=10) or both (N=3). Changes in head movement symmetry between conditions were small and inconsistent. Changes in pelvic movement symmetry were small and showed significant differences between shoeing stages (SI: P=0.013, MinDiff: P=0.04) with most symmetrical pelvic movement after trimming. In military working horses with high frequency shoeing small changes in movement symmetry were measured. All significant changes involved trimming, which indicates that future studies should in particular assess changes before/after trimming and investigate longer shoeing intervals. PMID- 27358310 TI - Schnitzler Syndrome Without a Monoclonal Gammopathy: A Case Report. AB - BACKGROUND: Schnitzler syndrome (SS) is a rare autoinflammatory disorder characterized by a recurrent urticarial rash and a monoclonal immunoglobulin M gammopathy, as well as 2 of the following minor criteria: recurrent fever (>38 degrees C), objective signs of abnormal bone remodeling, elevated C-reactive protein level or leukocytosis, and a neutrophilic infiltrate on skin biopsy. Alternatively, a monoclonal immunoglobulin G gammopathy may be present along with 3 minor criteria for diagnosis. OBJECTIVE: To report a rare case of SS without monoclonal gammopathy and inform physicians of this possible clinical presentation so that treatment is not delayed. METHODS: We report a case of a 62 year-old white man with a clinical diagnosis of SS without monoclonal gammopathy. He presented with chronic urticaria unresponsive to conventional therapy. RESULTS AND CONCLUSIONS: To our knowledge, there have only been 3 case reports of SS in the absence of monoclonal gammopathy documented in the literature. SS should be considered based on clinical presentation, even in the absence of monoclonal gammopathy, to facilitate appropriate management. PMID- 27358311 TI - Primary Cutaneous B-Cell Lymphoma in Young Monozygotic Twins: A Case Report. AB - Although familial aggregation of lymphoproliferative disorders has been described, heredity has not been implicated in the etiology of primary cutaneous B-cell lymphomas (PCBCL). We report herein the first case of 2 young monozygotic twins with PCBCL. The first twin was an 18-year-old woman when she presented with multiple skin nodules on the thorax and head. Histology showed an atypical small B-cell proliferation, consistent with primary cutaneous marginal zone lymphoma (PCMZL). Molecular genetics studies demonstrated B-cell clonality. Seven years later, the second twin developed her first lesion that was histologically similar to that of her twin. She subsequently developed other clinically similar lesions. Histology was consistent with PCMZL and showed B-cell clonality. Occurrence of PCBCL in these monozygotic twins raises the possibility of a genetic risk factor. Further study of such rare cases may offer valuable insights into the molecular basis of the etiology and pathogenesis of this unusual disorder. PMID- 27358312 TI - A Case of Cutaneous B-Cell Lymphoma in Longstanding Systemic Lupus Erythematosus. AB - BACKGROUND: The association between lymphoproliferative malignancies and autoimmune rheumatological diseases, such as systemic lupus erythematosus (SLE), remains of great interest. It is known that individuals with immune dysregulation also have an increased risk of lymphoma. OBJECTIVE: To report a case of primary cutaneous diffuse large B-cell lymphoma of the leg type associated with longstanding SLE, as well as to review the literature for similar cases. METHODS: A PubMed search was done using the following search terms: lupus and B-cell lymphoma. RESULTS: Although several studies show that non-Hodgkin lymphoma is significantly increased in SLE, there is currently no literature reporting specifically on the risk of primary cutaneous lymphomas in patients with SLE. CONCLUSION: Our report highlights the possibility that patients with autoimmune disease are at increased risk of not only the classic forms of non-Hodgkin lymphoma but also primary cutaneous B-cell lymphomas. PMID- 27358313 TI - Relating normalization to neuronal populations across cortical areas. AB - Normalization, which divisively scales neuronal responses to multiple stimuli, is thought to underlie many sensory, motor, and cognitive processes. In every study where it has been investigated, neurons measured in the same brain area under identical conditions exhibit a range of normalization, ranging from suppression by nonpreferred stimuli (strong normalization) to additive responses to combinations of stimuli (no normalization). Normalization has been hypothesized to arise from interactions between neuronal populations, either in the same or different brain areas, but current models of normalization are not mechanistic and focus on trial-averaged responses. To gain insight into the mechanisms underlying normalization, we examined interactions between neurons that exhibit different degrees of normalization. We recorded from multiple neurons in three cortical areas while rhesus monkeys viewed superimposed drifting gratings. We found that neurons showing strong normalization shared less trial-to-trial variability with other neurons in the same cortical area and more variability with neurons in other cortical areas than did units with weak normalization. Furthermore, the cortical organization of normalization was not random: neurons recorded on nearby electrodes tended to exhibit similar amounts of normalization. Together, our results suggest that normalization reflects a neuron's role in its local network and that modulatory factors like normalization share the topographic organization typical of sensory tuning properties. PMID- 27358314 TI - Reduced frontal theta oscillations indicate altered crossmodal prediction error processing in schizophrenia. AB - Our brain generates predictions about forthcoming stimuli and compares predicted with incoming input. Failures in predicting events might contribute to hallucinations and delusions in schizophrenia (SZ). When a stimulus violates prediction, neural activity that reflects prediction error (PE) processing is found. While PE processing deficits have been reported in unisensory paradigms, it is unknown whether SZ patients (SZP) show altered crossmodal PE processing. We measured high-density electroencephalography and applied source estimation approaches to investigate crossmodal PE processing generated by audiovisual speech. In SZP and healthy control participants (HC), we used an established paradigm in which high- and low-predictive visual syllables were paired with congruent or incongruent auditory syllables. We examined crossmodal PE processing in SZP and HC by comparing differences in event-related potentials and neural oscillations between incongruent and congruent high- and low-predictive audiovisual syllables. In both groups event-related potentials between 206 and 250 ms were larger in high- compared with low-predictive syllables, suggesting intact audiovisual incongruence detection in the auditory cortex of SZP. The analysis of oscillatory responses revealed theta-band (4-7 Hz) power enhancement in high- compared with low-predictive syllables between 230 and 370 ms in the frontal cortex of HC but not SZP. Thus aberrant frontal theta-band oscillations reflect crossmodal PE processing deficits in SZ. The present study suggests a top down multisensory processing deficit and highlights the role of dysfunctional frontal oscillations for the SZ psychopathology. PMID- 27358315 TI - Competition between movement plans increases motor variability: evidence of a shared resource for movement planning. AB - Do movement plans, like representations in working memory, share a limited pool of resources? If so, the precision with which each individual movement plan is specified should decrease as the total number of movement plans increases. To explore this, human participants made speeded reaching movements toward visual targets. We examined if preparing one movement resulted in less variability than preparing two movements. The number of planned movements was manipulated in a delayed response cueing procedure that limited planning to a single target (experiment 1) or hand (experiment 2) or required planning of movements toward two targets (or with two hands). For both experiments, initial movement direction variability was higher in the two-plan condition than in the one-plan condition, demonstrating a cost associated with planning multiple movements, consistent with the limited resource hypothesis. In experiment 3, we showed that the advantage in initial variability of preparing a single movement was present only when the trajectory could be fully specified. This indicates that the difference in variability between one and two plans reflects the specification of full motor plans, not a general preparedness to move. The precision cost related to concurrent plans represents a novel constraint on motor preparation, indicating that multiple movements cannot be planned independently, even if they involve different limbs. PMID- 27358316 TI - Pain anticipatory phenomena in patients with central poststroke pain: a magnetoencephalography study. AB - Central poststroke pain (CPSP) is characterized by hemianesthesia associated with unrelenting chronic pain. The final pain experience stems from interactions between sensory, affective, and cognitive components of chronic pain. Hence, managing CPSP will require integrated approaches aimed not only at the sensory but also the affective-cognitive spheres. A better understanding of the brain's processing of pain anticipation is critical for the development of novel therapeutic approaches that target affective-cognitive networks and alleviate pain-related disability. We used magnetoencephalography (MEG) to characterize the neural substrates of pain anticipation in patients suffering from intractable CPSP. Simple visual cues evoked anticipation while patients awaited impending painful (PS), nonpainful (NPS), or no stimulus (NOS) to their nonaffected and affected extremities. MEG responses were studied at gradiometer level using event related fields analysis and time-frequency oscillatory analysis upon source localization. On the nonaffected side, significantly greater responses were recorded during PS. PS (vs. NPS and NOS) exhibited significant parietal and frontal cortical activations in the beta and gamma bands, respectively, whereas NPS (vs. NOS) displayed greater activation in the orbitofrontal cortex. On the affected extremity, PS (vs. NPS) did not show significantly greater responses. These data suggest that anticipatory phenomena can modulate neural activity when painful stimuli are applied to the nonaffected extremity but not the affected extremity in CPSP patients. This dichotomy may stem from the chronic effects of pain on neural networks leading to habituation or saturation. Future clinically effective therapies will likely be associated with partial normalization of the neurophysiological correlates of pain anticipation. PMID- 27358317 TI - Functional evidence for a direct excitatory projection from the lateral habenula to the ventral tegmental area in the rat. AB - The lateral habenula, a phylogenetically conserved epithalamic structure, is activated by aversive stimuli and reward omission. Excitatory efferents from the lateral habenula predominately inhibit midbrain dopamine neuronal firing through a disynaptic, feedforward inhibitory mechanism involving the rostromedial tegmental nucleus. However, the lateral habenula also directly targets dopamine neurons within the ventral tegmental area, suggesting that opposing actions may result from increased lateral habenula activity. In the present study, we tested the effect of habenular efferent stimulation on dopamine and nondopamine neurons in the ventral tegmental area of Sprague-Dawley rats using a parasagittal brain slice preparation. Single pulse stimulation of the fasciculus retroflexus excited 48% of dopamine neurons and 51% of nondopamine neurons in the ventral tegmental area of rat pups. These proportions were not altered by excision of the rostromedial tegmental nucleus and were evident in both cortical- and striatal projecting dopamine neurons. Glutamate receptor antagonists blocked this excitation, and fasciculus retroflexus stimulation elicited evoked excitatory postsynaptic potentials with a nearly constant onset latency, indicative of a monosynaptic, glutamatergic connection. Comparison of responses in rat pups and young adults showed no significant difference in the proportion of neurons excited by fasciculus retroflexus stimulation. Our data indicate that the well known, indirect inhibitory effect of lateral habenula activation on midbrain dopamine neurons is complemented by a significant, direct excitatory effect. This pathway may contribute to the role of midbrain dopamine neurons in processing aversive stimuli and salience. PMID- 27358318 TI - Adaptive muscle plasticity of a remaining agonist following denervation of its close synergists in a model of complete spinal cord injury. AB - Complete spinal cord injury (SCI) alters the contractile properties of skeletal muscle, and although exercise can induce positive changes, it is unclear whether the remaining motor system can produce adaptive muscle plasticity in response to a subsequent peripheral nerve injury. To address this, the nerve supplying the lateral gastrocnemius (LG) and soleus muscles was sectioned unilaterally in four cats that had recovered hindlimb locomotion after spinal transection. In these spinal cats, kinematics and electromyography (EMG) were collected before and for 8 wk after denervation. Muscle histology was performed on LG and medial gastrocnemius (MG) bilaterally in four spinal and four intact cats. In spinal cats, cycle duration for the hindlimb ipsilateral or contralateral to the denervation could be significantly increased or decreased compared with predenervation values. Stance duration was generally increased and decreased for the contralateral and ipsilateral hindlimbs, respectively. The EMG amplitude of MG was significantly increased bilaterally after denervation and remained elevated 8 wk after denervation. In spinal cats the ipsilateral LG was significantly smaller than the contralateral LG, whereas the ipsilateral MG weighed significantly more than the contralateral MG. Histological characterizations revealed significantly larger fiber areas for type IIa fibers of the ipsilateral MG in three of four spinal cats. Microvascular density in the ipsilateral MG was significantly higher than in the contralateral MG. In intact cats, no differences were found for muscle weight, fiber area, or microvascular density between homologous muscles. Therefore, the remaining motor system after complete SCI retains the ability to produce adaptive muscle plasticity. PMID- 27358319 TI - Spreading depolarization in the brain of Drosophila is induced by inhibition of the Na+/K+-ATPase and mitigated by a decrease in activity of protein kinase G. AB - Spreading depolarization (SD) is characterized by a massive redistribution of ions accompanied by an arrest in electrical activity that slowly propagates through neural tissue. It has been implicated in numerous human pathologies, including migraine, stroke, and traumatic brain injury, and thus the elucidation of control mechanisms underlying the phenomenon could have many health benefits. Here, we demonstrate the occurrence of SD in the brain of Drosophila melanogaster, providing a model system, whereby cellular mechanisms can be dissected using molecular genetic approaches. Propagating waves of SD were reliably induced by disrupting the extracellular potassium concentration ([K(+)]o), either directly or by inhibition of the Na(+)/K(+)-ATPase with ouabain. The disturbance was monitored by recording the characteristic surges in [K(+)]o using K(+)-sensitive microelectrodes or by monitoring brain activity by measuring direct current potential. With the use of wild-type flies, we show that young adults are more resistant to SD compared with older adults, evidenced by shorter bouts of SD activity and attenuated [K(+)]o disturbances. Furthermore, we show that the susceptibility to SD differs between wild-type flies and w1118 mutants, demonstrating that our ouabain model is influenced by genetic strain. Lastly, flies with low levels of protein kinase G (PKG) had increased latencies to onset of both ouabain-induced SD and anoxic depolarization compared with flies with higher levels. Our findings implicate the PKG pathway as a modulator of SD in the fly brain, and given the conserved nature of the signaling pathway, it could likely play a similar role during SD in the mammalian central nervous system. PMID- 27358320 TI - A step toward understanding the human ventral visual pathway. AB - The human ventral visual pathway is implicated in higher order form processing, but the organizational principles within this region are not yet well understood. Recently, Lafer-Sousa, Conway, and Kanwisher (J Neurosci 36: 1682-1697, 2016) used functional magnetic resonance imaging to demonstrate that functional responses in the human ventral visual pathway share a broad homology with the those in macaque inferior temporal cortex, providing new evidence supporting the validity of the macaque as a model of the human visual system in this region. In addition, these results give new clues for understanding the organizational principles within the ventral visual pathway and the processing of higher order color and form, suggesting new avenues for research into this cortical region. PMID- 27358323 TI - The * of Awareness. PMID- 27358322 TI - Gene Editing: Powerful New Tools for Nephrology Research and Therapy. AB - Biologic research is experiencing a transformation brought about by the ability of programmable nucleases to manipulate the genome. In the recently developed CRISPR/Cas system, short RNA sequences guide the endonuclease Cas9 to any location in the genome, causing a DNA double-strand break (DSB). Repair of DSBs allows the introduction of targeted genetic manipulations with high precision. Cas9-mediated gene editing is simple, scalable, and rapid, and it can be applied to virtually any organism. Here, we summarize the development of modern gene editing techniques and the biology of DSB repair on which these techniques are based. We discuss technical points in applying this technology and review its use in model organisms. Finally, we describe prospects for the use of gene editing to treat human genetic diseases. This technology offers tremendous promise for equipping the nephrology research community to better model and ultimately, treat kidney diseases. PMID- 27358324 TI - Geometrical Factors in the Perception of Sacredness. AB - Geometrical and environmental factors in the perception of sacredness, dominance, and attractiveness were assessed by 137 participants in five tests. In the first test, a two-alternative forced-choice paradigm was used to test the perception of sacredness, dominance, and attractiveness in geometrical figures differing in shape, verticality, size, and symmetry. Verticality, symmetry, and convexity were found to be important factors in the perception of sacredness. In the second test, participants had to mark the point inside geometrical surfaces that was perceived as most sacred, dominant, and attractive. The top and the center areas were associated with sacredness, dominance, and attractiveness. In the third test, peaks and elevated regions in landscapes were evaluated as more sacred, dominant, and attractive than valley regions. In the fourth test, three figures sharing the same area but differing in horizontal and vertical orientation were evaluated on eight scales. The vertical figure was evaluated as more sacred, dominant, and attractive than the horizontal figure. The fifth test demonstrated the significant role of space seclusion and inaccessibility in the perception of sacredness. Geometrical factors in the perception of sacredness, dominance, and attractiveness were largely overlapping. PMID- 27358321 TI - Vestibular and oculomotor influences on visual dependency. AB - The degree to which a person relies on visual stimuli for spatial orientation is termed visual dependency (VD). VD is considered a perceptual trait or cognitive style influenced by psychological factors and mediated by central reweighting of the sensory inputs involved in spatial orientation. VD is often measured with the rod-and-disk test, in which participants align a central rod to the subjective visual vertical (SVV) in the presence of a background that is either stationary or rotating around the line of sight-dynamic SVV. Although this task has been employed to assess VD in health and vestibular disease, what effect torsional nystagmic eye movements may have on individual performance is unknown. Using caloric ear irrigation, 3D video-oculography, and the rod-and-disk test, we show that caloric torsional nystagmus modulates measures of VD and demonstrate that increases in tilt after irrigation are positively correlated with changes in ocular torsional eye movements. When the direction of the slow phase of the torsional eye movement induced by the caloric is congruent with that induced by the rotating visual stimulus, there is a significant increase in tilt. When these two torsional components are in opposition, there is a decrease. These findings show that measures of VD can be influenced by oculomotor responses induced by caloric stimulation. The findings are of significance for clinical studies, as they indicate that VD, which often increases in vestibular disorders, is modulated not only by changes in cognitive style but also by eye movements, in particular nystagmus. PMID- 27358325 TI - Special focus on precision medicine informatics and education. PMID- 27358326 TI - Focusing on informatics education. PMID- 27358327 TI - Creating advanced health informatics certification. AB - In 2005, AMIA leaders and members concluded that certification of advanced health informatics professionals would offer value to individual practitioners, organizations that hire them, and society at large. AMIA's work to create advanced informatics certification began by leading a successful effort to create the clinical informatics subspecialty for American Board of Medical Specialties board-certified physicians. Since 2012, AMIA has been working to establish advanced health informatics certification (AHIC) for all health informatics practitioners regardless of their primary discipline. In November 2015, AMIA completed the first of 3 key tasks required to establish AHIC, with the AMIA Board of Directors' endorsement of proposed eligibility requirements. This AMIA Board white paper describes efforts to establish AHIC, reports on the current status of AHIC components, and provides a context for the proposed AHIC eligibility requirements. PMID- 27358329 TI - The scope of health informatics and the Advanced Health Informatics Certification. PMID- 27358328 TI - Eligibility requirements for advanced health informatics certification. AB - AMIA is leading the effort to strengthen the health informatics profession by creating an advanced health informatics certification (AHIC) for individuals whose informatics work directly impacts the practice of health care, public health, or personal health. The AMIA Board of Directors has endorsed a set of proposed AHIC eligibility requirements that will be presented to the future AHIC certifying entity for adoption. These requirements specifically establish who will be eligible to sit for the AHIC examination and more generally signal the depth and breadth of knowledge and experience expected from certified individuals. They also inform the development of the accreditation process and provide guidance to graduate health informatics programs as well as individuals interested in pursuing AHIC. AHIC eligibility will be determined by practice focus, education in primary field and health informatics, and significant health informatics experience. PMID- 27358330 TI - Can We Rely on Predicted Basal Metabolic Rate in Patients With Intestinal Failure on Home Parenteral Nutrition? AB - BACKGROUND AND AIMS: Intestinal failure (IF) is a serious and common complication of short bowel syndrome with patients depending on parenteral nutrition (PN) support. Effective nutrition management requires an accurate estimation of the patient's basal metabolic rate (BMR) to avoid underfeeding or overfeeding. However, indirect calorimetry, considered the gold standard for BMR assessment, is a time- and resource-consuming procedure. Consequently, several equations for prediction of BMR have been developed in different settings, but their accuracy in patients with IF are yet to be investigated. We evaluated the accuracy of predicted BMR in clinically stable patients with IF dependent on home parenteral nutrition (HPN). METHODS: In total, 103 patients with IF were included. We used indirect calorimetry for assessment of BMR and calculated predicted BMR using different equations based on anthropometric and/or bioelectrical impedance parameters. The accuracy of predicted BMR was evaluated using Bland-Altman analysis with measured BMR as the gold standard. RESULTS: The average measured BMR was 1272 +/- 245 kcal/d. The most accurate estimations of BMR were obtained using the Harris-Benedict equation (mean bias, 14 kcal/d [ P = .28]; limits of agreement [LoA], -238 to 266 kcal/d) and the Johnstone equation (mean bias, -16 kcal/d [ P = .24]; LoA, -285 to 253 kcal/d). For both equations, 67% of patients had a predicted BMR from 90%-110% All other equations demonstrated a statistically and clinically significant difference between measured and predicted BMR. CONCLUSIONS: The Harris-Benedict and Johnstone equations reliably predict BMR in two-thirds of clinically stable patients with IF on HPN. PMID- 27358331 TI - Toward the Development of Predictive Equations for Resting Metabolic Rate in Acutely Ill Spontaneously Breathing Patients. AB - BACKGROUND: There are many equations used for calculating energy needs of nutrition support patients but few developed specifically for the subset of spontaneously breathing acutely ill patients. The purpose of the current study was to validate existing equations and to start developing new equations for this cohort. METHODS: Acutely ill patients not requiring mechanical ventilation had their resting metabolic rate measured using an indirect calorimeter. Metabolic rate was also calculated using the Mifflin-St Jeor equation, the Ireton-Jones equation for spontaneously breathing patients, and a modification of the Penn State equation in which the minute ventilation-dependent variable was removed. These calculated values were compared with measured expenditure and considered accurate if they fell within 10% of the measurement. RESULTS: Fifty-five patients were measured successfully. The modified Penn State equation was accurate in 71% of patients compared with 44% for Ireton-Jones and 42% for Mifflin-St Jeor. Several forms of a new equation were outlined but not validated. The equation with the highest R2 (0.82) was as follows: resting metabolic rate (kcal/d) = weight in kg (20) - age in years (3) + male sex (197) + body mass index in kg/m2 (25.9) + mean heart rate in beats/min (9.4) + 89. CONCLUSIONS: A modification of the Penn State equation for predicting resting metabolic rate was shown to accurately predict resting metabolic rate in acutely ill, spontaneously breathing patients if body mass index was >=20.5 kg/m2. A new set of population-specific equations was outlined but should not be used until validated. PMID- 27358332 TI - Mitochondrial Function in an In Vitro Model of Skeletal Muscle of Patients With Protracted Critical Illness and Intensive Care Unit-Acquired Weakness. AB - BACKGROUND: Functional mitochondria in skeletal muscle of patients with protracted critical illness and intensive care unit-acquired weakness are depleted, but remaining mitochondria have increased functional capacities of respiratory complexes II and III. This can be an adaptation to relative abundancy of fatty acid over glucose caused by insulin resistance. We hypothesized that the capacity of muscle mitochondria to oxidize fatty acid is increased in protracted critical illness. METHODS: We assessed fatty acid oxidation (FAO) and mitochondrial functional indices in vitro by using extracellular flux analysis in cultured myotubes obtained by isolating and culturing satellite cells from vastus lateralis muscle biopsy samples from patients with ICU-acquired weakness (n = 6) and age-matched healthy controls (n = 7). Bioenergetic measurements were performed at baseline and after 6 days of exposure to free fatty acids (FFAs). RESULTS: Mitochondrial density in myotubes from ICU patients was 69% of healthy controls ( P = .051). After adjustment to mitochondrial content, there were no differences in adenosine triphosphate (ATP) synthesis or the capacity and coupling of the respiratory chain. FAO capacity in ICU patients was 157% of FAO capacity in controls ( P = .015). In myotubes of ICU patients, unlike healthy controls, the exposure to FFA significantly ( P = .009) increased maximum respiratory chain capacity. CONCLUSION: In an in vitro model of skeletal muscle of patients with protracted critical illness, we have shown signs of adaptation to increased FAO. Even in the presence of glucose and insulin, elevation of FFAs in the extracellular environment increased maximal capacity of the respiratory chain. PMID- 27358334 TI - Stem cells in amyotrophic lateral sclerosis: Ready for prime time? PMID- 27358333 TI - International consensus guidance for management of myasthenia gravis: Executive summary. AB - OBJECTIVE: To develop formal consensus-based guidance for the management of myasthenia gravis (MG). METHODS: In October 2013, the Myasthenia Gravis Foundation of America appointed a Task Force to develop treatment guidance for MG, and a panel of 15 international experts was convened. The RAND/UCLA appropriateness methodology was used to develop consensus guidance statements. Definitions were developed for goals of treatment, minimal manifestations, remission, ocular MG, impending crisis, crisis, and refractory MG. An in-person panel meeting then determined 7 treatment topics to be addressed. Initial guidance statements were developed from literature summaries. Three rounds of anonymous e-mail votes were used to attain consensus on guidance statements modified on the basis of panel input. RESULTS: Guidance statements were developed for symptomatic and immunosuppressive treatments, IV immunoglobulin and plasma exchange, management of impending and manifest myasthenic crisis, thymectomy, juvenile MG, MG associated with antibodies to muscle-specific tyrosine kinase, and MG in pregnancy. CONCLUSION: This is an international formal consensus of MG experts intended to be a guide for clinicians caring for patients with MG worldwide. PMID- 27358336 TI - US health insurance is an obstacle to disease-modifying treatments in MS. PMID- 27358335 TI - Transplantation of spinal cord-derived neural stem cells for ALS: Analysis of phase 1 and 2 trials. AB - OBJECTIVE: To test the safety of spinal cord transplantation of human stem cells in patients with amyotrophic lateral sclerosis (ALS) with escalating doses and expansion of the trial to multiple clinical centers. METHODS: This open-label trial included 15 participants at 3 academic centers divided into 5 treatment groups receiving increasing doses of stem cells by increasing numbers of cells/injection and increasing numbers of injections. All participants received bilateral injections into the cervical spinal cord (C3-C5). The final group received injections into both the lumbar (L2-L4) and cervical cord through 2 separate surgical procedures. Participants were assessed for adverse events and progression of disease, as measured by the ALS Functional Rating Scale-Revised, forced vital capacity, and quantitative measures of strength. Statistical analysis focused on the slopes of decline of these phase 2 trial participants alone or in combination with the phase 1 participants (previously reported), comparing these groups to 3 separate historical control groups. RESULTS: Adverse events were mostly related to transient pain associated with surgery and to side effects of immunosuppressant medications. There was one incident of acute postoperative deterioration in neurologic function and another incident of a central pain syndrome. We could not discern differences in surgical outcomes between surgeons. Comparisons of the slopes of decline with the 3 separate historical control groups showed no differences in mean rates of progression. CONCLUSIONS: Intraspinal transplantation of human spinal cord-derived neural stem cells can be safely accomplished at high doses, including successive lumbar and cervical procedures. The procedure can be expanded safely to multiple surgical centers. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with ALS, spinal cord transplantation of human stem cells can be safely accomplished and does not accelerate the progression of the disease. This study lacks the precision to exclude important benefit or safety issues. PMID- 27358337 TI - Presymptomatic cognitive decline in familial frontotemporal dementia: A longitudinal study. AB - OBJECTIVE: In this prospective cohort study, we performed a 2-year follow-up study with neuropsychological assessment in the presymptomatic phase of familial frontotemporal dementia (FTD) due to GRN and MAPT mutations to explore the prognostic value of neuropsychological assessment in the earliest FTD disease stages. METHODS: Healthy, at-risk, first-degree relatives of patients with FTD who had a MAPT (n = 13) or GRN mutation (n = 30) and healthy controls (n = 39) underwent neuropsychological assessment at baseline and 2-year follow-up. We investigated baseline and longitudinal differences, as well as relationship with age and estimated years before symptom onset. RESULTS: At baseline, GRN mutation carriers showed lower scores on mental processing speed than healthy controls (p = 0.043). Two years later, MAPT mutation carriers showed a steeper decline than GRN mutation carriers on social cognition (p = 0.002). Older age was related to cognitive decline in visuoconstruction (p = 0.005) and social cognition (p = 0.026) in MAPT. Memory significantly declined from 8 to 6 years before estimated symptom onset in MAPT and GRN mutation carriers, respectively, and language and social cognition declined only in MAPT mutation carriers from 7 to 5 years before estimated symptom onset, respectively (p < 0.05). CONCLUSIONS: Using longitudinal neuropsychological assessment, we detected gene-specific neuropsychological patterns of decline in, e.g., social cognition, memory, and visuoconstruction. Our results confirm the prognostic value of neuropsychological assessment as a potential clinical biomarker in the presymptomatic phase of familial FTD. PMID- 27358340 TI - Treating myasthenia on consensus guide: Helpful and challenging but still unfinished business. PMID- 27358338 TI - Health insurance affects the use of disease-modifying therapy in multiple sclerosis. AB - OBJECTIVE: To evaluate the association between health insurance coverage and disease-modifying therapy (DMT) use for multiple sclerosis (MS). METHODS: In 2014, we surveyed participants in the North American Research Committee on MS registry regarding health insurance coverage. We investigated associations between negative insurance change and (1) the type of insurance, (2) DMT use, (3) use of free/discounted drug programs, and (4) insurance challenges using multivariable logistic regressions. RESULTS: Of 6,662 respondents included in the analysis, 6,562 (98.5%) had health insurance, but 1,472 (22.1%) reported negative insurance change compared with 12 months earlier. Respondents with private insurance were more likely to report negative insurance change than any other insurance. Among respondents not taking DMTs, 6.1% cited insurance/financial concerns as the sole reason. Of respondents taking DMTs, 24.7% partially or completely relied on support from free/discounted drug programs. Of respondents obtaining DMTs through insurance, 3.3% experienced initial insurance denial of DMT use, 2.3% encountered insurance denial of DMT switches, and 1.6% skipped or split doses because of increased copay. For respondents with relapsing-remitting MS, negative insurance change increased their odds of not taking DMTs (odds ratio [OR] 1.50; 1.16-1.93), using free/discounted drug programs for DMTs (OR 1.89; 1.40-2.57), and encountering insurance challenges (OR 2.48; 1.64-3.76). CONCLUSIONS: Insurance coverage affects DMT use for persons with MS, and use of free/discounted drug programs is substantial and makes economic analysis that ignores these supplements potentially inaccurate. The rising costs of drugs and changing insurance coverage adversely affect access to treatment for persons with MS. PMID- 27358339 TI - Detecting depression in Parkinson disease: A systematic review and meta-analysis. AB - BACKGROUND: Failure to detect depression in patients with Parkinson disease (PD) can lead to worsened outcomes for patients and caregivers. Accurate identification of depression would enable practitioners to provide comprehensive care for their patients with PD. METHODS: Our objective was to examine the diagnostic accuracy of tools for detecting depression in adult outpatients with PD. We searched MEDLINE, PsycINFO, and EMBASE (inception to December 1, 2015), gray literature, and bibliographies of included studies. The pooled prevalence of depression across studies and diagnostic accuracy estimates were calculated using random-effects models. Diagnostic accuracy estimates were calculated across the best-reported cutoffs from each study and across specific cutoffs, when feasible. RESULTS: Out of 8,184 citations, 21 studies were included, evaluating 24 tools, with 4 amenable to meta-analysis. The pooled prevalence of major depression was 22.9% (95% confidence interval [CI] 18.1-27.7). The 15-item Geriatric Depression Scale (GDS-15) had a pooled sensitivity of 0.81 (95% CI 0.64-0.91) and specificity of 0.91 (95% CI 0.87-0.94). The most sensitive cutoff for the GDS-15 was 5 at 0.91 (95% CI 0.83-1.00). The Beck Depression Inventory I/Ia had a pooled sensitivity of 0.79 (95% CI 0.61-0.90) and specificity of 0.85 (95% CI 0.79 0.90). The Montgomery-Asberg Depression Rating Scale yielded a pooled sensitivity of 0.77 (95% CI 0.69-0.83) and specificity of 0.92 (95% CI 0.79-0.97). The Unified Parkinson's Disease Rating Scale had a pooled sensitivity of 0.72 (95% CI 0.64-0.79) and specificity of 0.80 (95% CI 0.70-0.87). All estimates had heterogeneity. CONCLUSIONS: There are several valid tools for detecting depression in patients with PD. Practitioners should choose one that fits their clinical practice. PMID- 27358341 TI - Tau PET in Alzheimer disease and mild cognitive impairment. AB - OBJECTIVE: To investigate the topographical distribution of tau pathology and its effect on functional and structural changes in patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) by using (18)F-AV-1451 PET. METHODS: We included 20 patients with AD, 15 patients with MCI, and 20 healthy controls, and performed neuropsychological function tests, MRI, as well as (18)F-florbetaben (for amyloid) and (18)F-AV-1451 (for tau) PET scans. By using the regional volume of-interest masks extracted from MRIs, regional binding values of standardized uptake value ratios and volumes were measured. We compared regional binding values among 3 diagnostic groups and identified correlations among the regional binding values, performance in each cognitive function test, and regional atrophy. RESULTS: (18)F-AV-1451 binding was increased only in the entorhinal cortex in patients with MCI, while patients with AD exhibited greater binding in most cortical regions. In the 35 patients with MCI and AD, (18)F-AV-1451 binding in most of the neocortex increased with a worsening of global cognitive function. The visual and verbal memory functions were associated with the extent of (18)F AV-1451 binding, especially in the medial temporal regions. The (18)F-AV-1451 binding also correlated with the severity of regional atrophy of the cerebral cortex. CONCLUSIONS: Tau PET imaging with (18)F-AV-1451 could serve as an in vivo biomarker for the evaluation of AD-related tau pathology and monitoring disease progression. The accumulation of pathologic tau is more closely related to functional and structural deterioration in the AD spectrum than beta-amyloid. PMID- 27358342 TI - Evaluation of pain and stress in healthy volunteers undergoing research lumbar punctures. PMID- 27358343 TI - Measuring Coping Behavior in Liver Transplant Candidates: A Psychometric Analysis of the Brief COPE. AB - Liver transplant candidates must cope with significant physiological and psychological challenges. The Brief COPE is a frequently used measure of coping behavior; however, knowledge of the scale's factor structure and construct validity is limited with regard to liver transplant candidates. This study assessed the validity of the Brief COPE in 120 liver transplant candidates using exploratory factor analysis. Results revealed a 6-factor solution, only 2 of which were consistent with the original scale assignments. Construct validity of the 6 Brief COPE scales yielded in this study was demonstrated. The results indicate that the Brief COPE is valid, reliable, and can be meaningfully interpreted in liver transplant patients. Future research should confirm this factor structure and examine its predictive validity prior to widespread use among liver transplant patients. Suggestions are presented for enhancing the care of transplant candidates by promoting the use of adaptive coping mechanisms to manage distress. PMID- 27358345 TI - Cyberchondria and adolescents. PMID- 27358344 TI - Risk Factors for Clostridium Difficile Diarrhea in Patients With Solid Organ Transplantation. AB - BACKGROUND: There is limited knowledge about specific risk factors for Clostridium difficile infection (CDI). METHOD: A retrospective study comparing cases of CDI in solid organ transplant (SOT) recipients with controls (SOT recipients who did not present CDI). RESULTS: Thirty patients with SOT from 1340 transplantation recipients had at least 1 episode of CDI (2.23%). The accumulated incidence was 3.06% in liver transplantation, 2.78% in lung transplantation, 2.36% in kidney transplantation, and 0.33% in heart transplantation. Seven (23%) cases occurred during the first 2 months. Fifteen (50%) cases were community acquired. Colonoscopy was performed in 6 (20%) cases, but pseudomembranes were observed in only 1 (16%) case. Independent variables found to be related to CDI were previous treatment with proton pump inhibitors (PPIs; odds ratio [OR] 5.5; 95% confidence interval [CI] 1.2-32.0), immunosuppressive regimen including mycophenolate (OR 5.2; 95%CI 1.1-18), hospitalization during the previous 3 months (OR 5.1; 95%CI 1.1-17), and antibiotic treatment during the previous month (OR 6.7; 95%CI 1.4-23). Five (16.7%) patients did not respond to the initial treatment. Recurrences were noted in 6 (20%) patients. CONCLUSIONS: Liver transplant recipients presented the highest incidence. Risk factors for CDI were previous treatment with PPIs, immunosuppressive regimen containing mycophenolate, prior hospitalization, and prior antibiotic treatment. PMID- 27358346 TI - Common Mental Disorders in Primary Health Care Units: Associated Factors and Impact on Quality of Life. AB - BACKGROUND: Considering the high worldwide prevalence of common mental disorders (CMDs), characterizing the association between CMD and quality of life (QoL) constitute a valuable measure to gauge patient's functional impairment due to CMD symptoms. OBJECTIVE: To investigate factors associated with the incidence of CMD and its impact on the QoL in primary health care (PHC) patients. DESIGN: Cross sectional study completed in a municipality in Brazil. Standardized tools included the Self-Reporting Questionnaire-20 to detect CMDs and the WHOQOL-brief to assess QoL, in addition to a sociodemographic and treatment-related questionnaire. RESULTS: A total of 41.4% of the patients met cutoff scores for a CMD, and the presence of a CMD was associated with female gender and marital status. Patients with CMDs had lower QoL scores than patients who were negative for a CMD. CONCLUSIONS: CMDs are highly prevalent in PHC settings and affect patients' QoL. The high frequency of CMD in those that seek care through PHC necessitate incorporating mental health services into the range of available services. PMID- 27358347 TI - Current Management of Cardiac Implantable Electronic Device Infections by Infectious Disease Specialists. AB - Management guidelines for cardiac implantable electronic device infections exist, but practice patterns of infectious disease (ID) specialists are not well known. We found that while many ID specialist practices mirror existing guidelines, a combination of complete device removal and prolonged antimicrobial therapy is favored when Staphylococcus aureus is involved. PMID- 27358348 TI - Middle East Respiratory Syndrome Coronavirus Infection During Pregnancy: A Report of 5 Cases From Saudi Arabia. AB - Little is known about the effects of Middle East respiratory syndrome coronavirus (MERS-CoV) during pregnancy. In Saudi Arabia, 5 cases of MERS-CoV infection among pregnant women were reviewed, and all cases resulted in adverse outcomes. MERS CoV infection during pregnancy may be associated with maternal and perinatal disease and death. PMID- 27358349 TI - Editorial Commentary: Potential Risks and Rewards With Prophylaxis for Clostridium difficile Infection. PMID- 27358350 TI - Predominance of Lactobacillus spp. Among Patients Who Do Not Acquire Multidrug Resistant Organisms. AB - BACKGROUND: The emergence and dissemination of multidrug-resistant organisms (MDROs) is a global threat. Characterizing the human microbiome among hospitalized patients and identifying unique microbial signatures among those patients who acquire MDROs may identify novel infection prevention strategies. METHODS: Adult patients admitted to 5 general medical-surgical floors at a 649 bed, tertiary care center in Boston, Massachusetts, were classified according to in-hospital antimicrobial exposure and MDRO colonization status. Within 48 hours of hospital admission (baseline) and at discharge (follow-up), rectal swab samples were obtained, and compared with samples from an external control group of healthy persons from the community. DNA was extracted from samples, next generation sequencing performed, and microbial community structure and taxonomic features assessed, comparing those who acquired MDROs and those who had not, and the external controls. RESULTS: Hospitalized patients (n = 44) had reduced microbial diversity and a greater abundance of Escherichia spp. and Enterococcus spp. than healthy controls (n = 26). Among hospitalized patients, 25 had no MDROs at the time of the baseline sample and were also exposed to antimicrobials. Among this group, 7 (28%) acquired >=1 MDRO; demographic and clinical characteristics were similar between MDRO-acquisition and MDRO-nonacquisition groups. Patients in the nonacquisition group had consistently higher Lactobacillus spp. abundance than those in the acquisition group (linear discriminant score, 3.97; P = .04). CONCLUSIONS: The fecal microbiota of the hospitalized subjects had abnormal community composition, and Lactobacillus spp. was associated with lack of MDRO acquisition, consistent with a protective role. PMID- 27358351 TI - Synergy, Salary, and Satisfaction: Benefits of Training in Critical Care Medicine and Infectious Diseases Gleaned From a National Pilot Survey of Dually Trained Physicians. AB - BACKGROUND: An increasing number of physicians are seeking dual training in critical care medicine (CCM) and infectious diseases (ID). Understanding experiences and perceptions of CCM-ID physicians could inform career choices and programmatic innovation. METHODS: All physicians trained and/or certified in both CCM and ID to date in the United States were sent a Web-based questionnaire in 2015. Responses enabled a cross-sectional analysis of physician demographics and training and practice characteristics and satisfaction. RESULTS: Of 202 CCM-ID physicians, 196 were alive and reachable. The response rate was 79%. Forty-six percent trained and 34% practice in the northeastern United States. Only 40% received dual training at the same institution. Eighty-three percent identified as either an intensivist with ID expertise (44%) or as equally an intensivist and ID physician (38%). Median salary was $265 000 (interquartile range [IQR], $215 000-$350 000). Practice settings were split between academic (45%) and community settings (42%). Two-thirds are clinicians but 62% conduct some research and 26% practice outpatient ID. Top reasons to dually specialize included clinical synergy (70%), procedural activity (50%), and less interest in pulmonology (49%). Although 38% cited less proficiency with bronchoscopy as a disadvantage, 87% seldom need pulmonary consultation in the intensive care unit. Median career satisfaction was 4 (IQR, 4-5) out of 5, and 76% would dually train again. CONCLUSIONS: CCM-ID graduates prefer the acute care setting, predominantly CCM or a combination of CCM and ID. They find combination training and practice to be synergistic and satisfying, but most have had to seek CCM and ID training independently at separate institutions. Given these findings, avenues for combined training in CCM-ID should be considered. PMID- 27358352 TI - Qualifications, Demographics, Satisfaction, and Future Capacity of the HIV Care Provider Workforce in the United States, 2013-2014. AB - BACKGROUND: The human immunodeficiency virus (HIV)-infected population in the United States is increasing by about 30 000 annually (new infections minus deaths). With improvements in diagnosis and engagement in care, additional qualified HIV care providers may be needed. METHODS: We surveyed a probability sample of 2023 US HIV care providers in 2013-2014, including those at Ryan White HIV/AIDS Program (RWHAP)-funded facilities and in private practices. We estimated future patient care capacity by comparing counts of providers entering and planning to leave practice within 5 years, and the number of patients under their care. RESULTS: Of surveyed providers, 1234 responded (adjusted response rate, 64%): 63% were white, 11% black, 11% Hispanic, and 16% other race/ethnicity; 37% were satisfied/very satisfied with salary/reimbursement, and 33% were satisfied/very satisfied with administrative time. Compared with providers in private practice, more providers at RWHAP-funded facilities were HIV specialists (71% vs 43%; P < .0001) and planned to leave HIV practice within 5 years (11% vs 4%; P = .0004). An estimated 190 more full-time equivalent providers (defined as 40 HIV clinical care hours per week) entered practice in the past 5 years than are expected to leave in the next 5 years. If these rates continue, by 2019 patient care capacity will increase by 65 000, compared with an increased requirement of at least 100 000. CONCLUSIONS: Projected workforce growth by 2019 will not accommodate the increased number of HIV-infected persons requiring care. RWHAP-funded facilities may face attrition of highly qualified providers. Dissatisfaction with salary/reimbursement and administrative burden is substantial, and black and Hispanic providers are underrepresented relative to HIV patients. PMID- 27358353 TI - Editorial Commentary: Infectious Diseases/Critical Care Medicine: Time to Embrace a New Subspecialty of Infectious Disease. PMID- 27358354 TI - Durable Viral Suppression and Transmission Risk Potential Among Persons With Diagnosed HIV Infection: United States, 2012-2013. AB - BACKGROUND: We examined durable viral suppression, cumulative viral load (VL) burden, and transmission risk potential among human immunodeficiency virus (HIV) diagnosed persons in care. METHODS: Using data from the National HIV Surveillance System from 17 jurisdictions with complete reporting of VL test results, we determined the percentage of persons in HIV care who achieved durable viral suppression (all VL results <200 copies/mL) and examined viremia copy-years and time spent above VL levels that increase the risk of HIV transmission during 2012 2013. RESULTS: Of 265 264 persons in HIV care in 2011, 238 641 had at least 2 VLs in 2012-2013. The median number of VLs per individual during the 2-year period was 5. Approximately 62% had durable viral suppression. The remaining 38% had high VL burden (geometric mean of viremia copy-years, 7261) and spent an average of 438 days, 316 days, and 215 days (60%, 43.2%, and 29.5% of the 2-year period) above 200, 1500, and 10 000 copies/mL. Women, blacks/African Americans, Hispanics/Latinos, persons with HIV infection attributed to transmission other than male-to-male sexual contact, younger age groups, and persons with gaps in care had higher viral burden and transmission risk potential. CONCLUSIONS: Two thirds of persons in HIV care had durable viral suppression during a 2-year period. One-third had high VL burden and spent substantial time above VL levels with increased risk of onward transmission. More intervention efforts are needed to improve retention in care and medication adherence so that more persons in HIV care achieve durable viral suppression. PMID- 27358355 TI - The Effect of a Nationwide Infection Control Program Expansion on Hospital-Onset Gram-Negative Rod Bacteremia in 130 Veterans Health Administration Medical Centers: An Interrupted Time-Series Analysis. AB - BACKGROUND: The Veterans Health Administration (VHA) introduced the Methicillin Resistant Staphylococcus aureus (MRSA) Prevention Initiative in March 2007. Although the initiative has been perceived as a vertical intervention focusing on MRSA, it also expanded infection prevention and control programs and resources. We aimed to assess the horizontal effect of the initiative on hospital-onset (HO) gram-negative rod (GNR) bacteremia. METHODS: This retrospective cohort included all patients who had HO bacteremia due to Escherichia coli, Klebsiella species, or Pseudomonas aeruginosa at 130 VHA facilities from January 2003 to December 2013. The effects were assessed using segmented linear regression with autoregressive error models, incorporating autocorrelation, immediate effect, and time before and after the initiative. Community-acquired (CA) bacteremia with same species was also analyzed as nonequivalent dependent controls. RESULTS: A total of 11 196 patients experienced HO-GNR bacteremia during the study period. There was a significant change of slope in HO-GNR bacteremia incidence rates from before the initiative (+0.3%/month) to after (-0.4%/month) (P < .01), while CA GNR incidence rates did not significantly change (P = .08). Cumulative effect of the intervention on HO-GNR bacteremia incidence rates at the end of the study period was estimated to be -43.2% (95% confidence interval, -51.6% to -32.4%). Similar effects were observed in subgroup analyses of each species and antimicrobial susceptibility profile. CONCLUSIONS: Within 130 VHA facilities, there was a sustained decline in HO-GNR bacteremia incidence rates after the implementation of the MRSA Prevention Initiative. As these organisms were not specifically targeted, it is likely that horizontal components of the initiative contributed to this decline. PMID- 27358356 TI - A Clinical Decision Tree to Predict Whether a Bacteremic Patient Is Infected With an Extended-Spectrum beta-Lactamase-Producing Organism. AB - BACKGROUND: Timely identification of extended-spectrum beta-lactamase (ESBL) bacteremia can improve clinical outcomes while minimizing unnecessary use of broad-spectrum antibiotics, including carbapenems. However, most clinical microbiology laboratories currently require at least 24 additional hours from the time of microbial genus and species identification to confirm ESBL production. Our objective was to develop a user-friendly decision tree to predict which organisms are ESBL producing, to guide appropriate antibiotic therapy. METHODS: We included patients >=18 years of age with bacteremia due to Escherichia coli or Klebsiella species from October 2008 to March 2015 at Johns Hopkins Hospital. Isolates with ceftriaxone minimum inhibitory concentrations >=2 ug/mL underwent ESBL confirmatory testing. Recursive partitioning was used to generate a decision tree to determine the likelihood that a bacteremic patient was infected with an ESBL producer. Discrimination of the original and cross-validated models was evaluated using receiver operating characteristic curves and by calculation of C statistics. RESULTS: A total of 1288 patients with bacteremia met eligibility criteria. For 194 patients (15%), bacteremia was due to a confirmed ESBL producer. The final classification tree for predicting ESBL-positive bacteremia included 5 predictors: history of ESBL colonization/infection, chronic indwelling vascular hardware, age >=43 years, recent hospitalization in an ESBL high-burden region, and >=6 days of antibiotic exposure in the prior 6 months. The decision tree's positive and negative predictive values were 90.8% and 91.9%, respectively. CONCLUSIONS: Our findings suggest that a clinical decision tree can be used to estimate a bacteremic patient's likelihood of infection with ESBL producing bacteria. Recursive partitioning offers a practical, user-friendly approach for addressing important diagnostic questions. PMID- 27358357 TI - Transmission of Balamuthia mandrillaris by Organ Transplantation. AB - BACKGROUND: During 2009 and 2010, 2 clusters of organ transplant-transmitted Balamuthia mandrillaris, a free-living ameba, were detected by recognition of severe unexpected illness in multiple recipients from the same donor. METHODS: We investigated all recipients and the 2 donors through interview, medical record review, and testing of available specimens retrospectively. Surviving recipients were tested and treated prospectively. RESULTS: In the 2009 cluster of illness, 2 kidney recipients were infected and 1 died. The donor had Balamuthia encephalitis confirmed on autopsy. In the 2010 cluster, the liver and kidney-pancreas recipients developed Balamuthia encephalitis and died. The donor had a clinical syndrome consistent with Balamuthia infection and serologic evidence of infection. In both clusters, the 2 asymptomatic recipients were treated expectantly and survived; 1 asymptomatic recipient in each cluster had serologic evidence of exposure that decreased over time. Both donors had been presumptively diagnosed with other neurologic diseases prior to organ procurement. CONCLUSIONS: Balamuthia can be transmitted through organ transplantation with an observed incubation time of 17-24 days. Clinicians should be aware of Balamuthia as a cause of encephalitis with high rate of fatality, and should notify public health departments and evaluate transplant recipients from donors with signs of possible encephalitis to facilitate early diagnosis and targeted treatment. Organ procurement organizations and transplant centers should be aware of the potential for Balamuthia infection in donors with possible encephalitis and also assess donors carefully for signs of neurologic infection that may have been misdiagnosed as stroke or as noninfectious forms of encephalitis. PMID- 27358358 TI - Evaluation of the C6 Lyme Enzyme Immunoassay for the Diagnosis of Lyme Disease in Children and Adolescents. AB - BACKGROUND: The commercially-available C6 Lyme enzyme immunoassay (EIA) has been approved to replace the standard whole-cell sonicate EIA as a first-tier test for the diagnosis of Lyme disease and has been suggested as a stand-alone diagnostic. However, the C6 EIA has not been extensively studied in pediatric patients undergoing evaluation for Lyme disease. METHODS: We collected discarded serum samples from children and adolescents (aged <=21 years) undergoing conventional 2 tiered testing for Lyme disease at a single hospital-based clinical laboratory located in an area endemic for Lyme disease. We performed a C6 EIA on all collected specimens, followed by a supplemental immunoblot if the C6 EIA result was positive but the whole-cell sonicate EIA result was negative. We defined a case of Lyme disease as either a clinician-diagnosed erythema migrans lesion or a positive standard 2-tiered serologic result in a patient with symptoms compatible with Lyme disease. We then compared the performance of the C6 EIA alone and as a first-tier test followed by immunoblot, with that of standard 2-tiered serology for the diagnosis of Lyme disease. RESULTS: Of the 944 specimens collected, 114 (12%) were from patients with Lyme disease. The C6 EIA alone had sensitivity similar to that of standard 2-tiered testing (79.8% vs 81.6% for standard 2 tiered testing; P = .71) with slightly lower specificity (94.2% vs 98.8% 2; P < .002). Addition of a supplemental immunoblot improved the specificity of the C6 EIA to 98.6%. CONCLUSIONS: For children and adolescents undergoing evaluation for Lyme disease, the C6 EIA could guide initial clinical decision making, although a supplemental immunoblot should still be performed. PMID- 27358359 TI - Arrhythmogenic right ventricular dysplasia/cardiomyopathy: arrhythmogenesis in the apparently normal heart? PMID- 27358360 TI - Non-vitamin K oral anticoagulants in patients with atrial fibrillation after cardiac surgery: the results of the European Heart Rhythm Association Survey. AB - The purpose of this European Heart Rhythm Association survey was to assess the current practice concerning the use of oral anticoagulation in patients with post operative atrial fibrillation (pre-existing or new-onset). The survey highlights the considerable heterogeneity of the type of anticoagulation, with 25% of the centres never using the non-vitamin K antagonist oral anticoagulants (NOACs) in this setting, as well the timing of oral anticoagulation initiation, the use and dosing of low-molecular-weight heparins, and the duration of anticoagulation when sinus rhythm is restored. One-third of the centres stated that they perceived that the risk of major pericardial bleeding requiring pericardiocentesis was higher when NOACs were used compared with vitamin K antagonists. Overall, the responding centres estimated the incidence of major pericardial haemorrhage to be 2.4%. More data are needed to inform practice guidelines in this field. PMID- 27358361 TI - Eutherians experienced elevated evolutionary rates in the immediate aftermath of the Cretaceous-Palaeogene mass extinction. AB - The effect of the Cretaceous-Palaeogene (K-Pg) mass extinction on the evolution of many groups, including placental mammals, has been hotly debated. The fossil record suggests a sudden adaptive radiation of placentals immediately after the event, but several recent quantitative analyses have reconstructed no significant increase in either clade origination rates or rates of character evolution in the Palaeocene. Here we use stochastic methods to date a recent phylogenetic analysis of Cretaceous and Palaeocene mammals and show that Placentalia likely originated in the Late Cretaceous, but that most intraordinal diversification occurred during the earliest Palaeocene. This analysis reconstructs fewer than 10 placental mammal lineages crossing the K-Pg boundary. Moreover, we show that rates of morphological evolution in the 5 Myr interval immediately after the K-Pg mass extinction are three times higher than background rates during the Cretaceous. These results suggest that the K-Pg mass extinction had a marked impact on placental mammal diversification, supporting the view that an evolutionary radiation occurred as placental lineages invaded new ecological niches during the Early Palaeocene. PMID- 27358362 TI - Inverse approach to estimating larval dispersal reveals limited population connectivity along 700 km of wave-swept open coast. AB - Demographic connectivity is fundamental to the persistence and resilience of metapopulations, but our understanding of the link between reproduction and recruitment is notoriously poor in open-coast marine populations. We provide the first evidence of high local retention and limited connectivity among populations spanning 700 km along an open coast in an upwelling system. Using extensive field measurements of fecundity, population size and settlement in concert with a Bayesian inverse modelling approach, we estimated that, on average, Petrolisthes cinctipes larvae disperse only 6.9 km (+/-25.0 km s.d.) from natal populations, despite spending approximately six weeks in an open-coast system that was once assumed to be broadly dispersive. This estimate differed substantially from our prior dispersal estimate (153.9 km) based on currents and larval duration and behaviour, revealing the importance of employing demographic data in larval dispersal estimates. Based on this estimate, we predict that demographic connectivity occurs predominantly among neighbouring populations less than 30 km apart. Comprehensive studies of larval production, settlement and connectivity are needed to advance an understanding of the ecology and evolution of life in the sea as well as to conserve ecosystems. Our novel approach provides a tractable framework for addressing these questions for species occurring in discrete coastal populations. PMID- 27358364 TI - Cellular and molecular remodelling of a host cell for vertical transmission of bacterial symbionts. AB - Various insects require intracellular bacteria that are restricted to specialized cells (bacteriocytes) and are transmitted vertically via the female ovary, but the transmission mechanisms are obscure. We hypothesized that, in the whitefly Bemisia tabaci, where intact bacteriocytes (and not isolated bacteria) are transferred to oocytes, the transmission mechanism would be evident as cellular and molecular differences between the nymph (pre-adult) and adult bacteriocytes. We demonstrate dramatic remodelling of bacteriocytes at the developmental transition from nymph to adulthood. This transition involves the loss of cell cell adhesion, high division rates to constant cell size and onset of cell mobility, enabling the bacteriocytes to crawl to the ovaries. These changes are accompanied by cytoskeleton reorganization and changes in gene expression: genes functioning in cell-cell adhesion display reduced expression and genes involved in cell division, cell motility and endocytosis/exocytosis have elevated expression in adult bacteriocytes, relative to nymph bacteriocytes. This study demonstrates, for the first time, how developmentally orchestrated remodelling of gene expression and correlated changes in cell behaviour underpin the capacity of bacteriocytes to mediate the vertical transmission and persistence of the symbiotic bacteria on which the insect host depends. PMID- 27358363 TI - A possible role of DNA methylation in functional divergence of a fast evolving duplicate gene encoding odorant binding protein 11 in the honeybee. AB - Although gene duplication is seen as the main path to evolution of new functions, molecular mechanisms by which selection favours the gain versus loss of newly duplicated genes and minimizes the fixation of pseudo-genes are not well understood. Here, we investigate in detail a duplicate honeybee gene obp11 belonging to a fast evolving insect gene family encoding odorant binding proteins (OBPs). We report that obp11 is expressed only in female bees in rare antennal sensilla basiconica in contrast to its tandem partner obp10 that is expressed in the brain in both females and males (drones). Unlike all other obp genes in the honeybee, obp11 is methylated suggesting that functional diversification of obp11 and obp10 may have been driven by an epigenetic mechanism. We also show that increased methylation in drones near one donor splice site that correlates with higher abundance of a transcript variant encoding a truncated OBP11 protein is one way of controlling its contrasting expression. Our data suggest that like in mammals and plants, DNA methylation in insects may contribute to functional diversification of proteins produced from duplicated genes, in particular to their subfunctionalization by generating complementary patterns of expression. PMID- 27358365 TI - How humans drive speciation as well as extinction. AB - A central topic for conservation science is evaluating how human activities influence global species diversity. Humanity exacerbates extinction rates. But by what mechanisms does humanity drive the emergence of new species? We review human mediated speciation, compare speciation and known extinctions, and discuss the challenges of using net species diversity as a conservation objective. Humans drive rapid evolution through relocation, domestication, hunting and novel ecosystem creation-and emerging technologies could eventually provide additional mechanisms. The number of species relocated, domesticated and hunted during the Holocene is of comparable magnitude to the number of observed extinctions. While instances of human-mediated speciation are known, the overall effect these mechanisms have upon speciation rates has not yet been quantified. We also explore the importance of anthropogenic influence upon divergence in microorganisms. Even if human activities resulted in no net loss of species diversity by balancing speciation and extinction rates, this would probably be deemed unacceptable. We discuss why, based upon 'no net loss' conservation literature-considering phylogenetic diversity and other metrics, risk aversion, taboo trade-offs and spatial heterogeneity. We conclude that evaluating speciation alongside extinction could result in more nuanced understanding of biosphere trends, clarifying what it is we actually value about biodiversity. PMID- 27358366 TI - Sexual cannibalism increases male material investment in offspring: quantifying terminal reproductive effort in a praying mantis. AB - Models of the evolution of sexual cannibalism argue that males may offset the cost of cannibalism if components of the male body are directly allocated to the eggs that they fertilize. We tested this idea in the praying mantid Tenodera sinensis Males and females were fed differently radiolabelled crickets and allowed to mate. Half of the pairs progressed to sexual cannibalism and we prevented cannibalism in the other half. We assess the relative allocation of both male-derived somatic materials and ejaculate materials into the eggs and soma of the female. Our results show that male somatic investment contributes to production of offspring. The eggs and reproductive tissues of cannibalistic females contained significantly more male-derived amino acids than those of non cannibalistic females, and there was an increase in the number of eggs produced subsequent to sexual cannibalism. Sexual cannibalism thus increases male material investment in offspring. We also show that males provide substantial investment via the ejaculate, with males passing about 25% of their radiolabelled amino acids to females via the ejaculate even in the absence of cannibalism. PMID- 27358367 TI - Elevated virulence of an emerging viral genotype as a driver of honeybee loss. AB - Emerging infectious diseases (EIDs) have contributed significantly to the current biodiversity crisis, leading to widespread epidemics and population loss. Owing to genetic variation in pathogen virulence, a complete understanding of species decline requires the accurate identification and characterization of EIDs. We explore this issue in the Western honeybee, where increasing mortality of populations in the Northern Hemisphere has caused major concern. Specifically, we investigate the importance of genetic identity of the main suspect in mortality, deformed wing virus (DWV), in driving honeybee loss. Using laboratory experiments and a systematic field survey, we demonstrate that an emerging DWV genotype (DWV B) is more virulent than the established DWV genotype (DWV-A) and is widespread in the landscape. Furthermore, we show in a simple model that colonies infected with DWV-B collapse sooner than colonies infected with DWV-A. We also identify potential for rapid DWV evolution by revealing extensive genome-wide recombination in vivo The emergence of DWV-B in naive honeybee populations, including via recombination with DWV-A, could be of significant ecological and economic importance. Our findings emphasize that knowledge of pathogen genetic identity and diversity is critical to understanding drivers of species decline. PMID- 27358369 TI - Cementing mussels to oysters in the pteriomorphian tree: a phylogenomic approach. AB - Mussels (Mytilida) are a group of bivalves with ancient origins and some of the most important commercial shellfish worldwide. Mytilida consists of approximately 400 species found in various littoral and deep-sea environments, and are part of the higher clade Pteriomorphia, but their exact position within the group has been unstable. The multiple adaptive radiations that occurred within Pteriomorphia have rendered phylogenetic classifications difficult and uncertainty remains regarding the relationships among most families. To address this phylogenetic uncertainty, novel transcriptomic data were generated to include all five orders of Pteriomorphia. Our results, derived from complex analyses of large datasets from 41 transcriptomes and evaluating possible pitfalls affecting phylogenetic reconstruction (matrix occupancy, heterogeneity, evolutionary rates, evolutionary models), consistently recover a well-supported phylogeny of Pteriomorphia, with the only exception of the most complete but smallest data matrix (Matrix 3: 51 genes, 90% gene occupancy). Maximum-likelihood and Bayesian mixture model analyses retrieve strong support for: (i) the monophyly of Pteriomorphia, (ii) Mytilida as a sister group to Ostreida, and (iii) Arcida as sister group to all other pteriomorphians. The basal position of Arcida is congruent with its shell microstructure (solely composed of aragonitic crystals), whereas Mytilida and Ostreida display a combination of a calcitic outer layer with an aragonitic inner layer composed of nacre tablets, the latter being secondarily lost in Ostreoidea. PMID- 27358368 TI - The oxidative cost of reproduction depends on early development oxidative stress and sex in a bird species. AB - In the early 2000s, a new component of the cost of reproduction was proposed: oxidative stress. Since then the oxidative cost of reproduction hypothesis has, however, received mixed support. Different arguments have been provided to explain this. Among them, the lack of a life-history perspective on most experimental tests was suggested. We manipulated the levels of a key intracellular antioxidant (glutathione) in captive zebra finches (Taeniopygia guttata) during a short period of early life and subsequently tested the oxidative cost of reproduction. Birds were allowed to mate freely in an outdoor aviary for several months. We repeatedly enlarged or reduced their broods to increase or reduce, respectively, breeding effort. Birds whose glutathione levels were reduced during growth showed higher erythrocyte resistance to free radical induced haemolysis when forced to rear enlarged broods. This supports the hypothesis predicting the occurrence of developing programmes matching early and adult environmental conditions to improve fitness. Moreover, adult males rearing enlarged broods endured higher plasma levels of lipid oxidative damage than control males, whereas adult females showed the opposite trend. As most previous studies reporting non-significant or opposite results used females only, we also discuss some sex-related particularities that may contribute to explain unexpected results. PMID- 27358370 TI - Light pollution is associated with earlier tree budburst across the United Kingdom. AB - The ecological impact of night-time lighting is of concern because of its well demonstrated effects on animal behaviour. However, the potential of light pollution to change plant phenology and its corresponding knock-on effects on associated herbivores are less clear. Here, we test if artificial lighting can advance the timing of budburst in trees. We took a UK-wide 13 year dataset of spatially referenced budburst data from four deciduous tree species and matched it with both satellite imagery of night-time lighting and average spring temperature. We find that budburst occurs up to 7.5 days earlier in brighter areas, with the relationship being more pronounced for later-budding species. Excluding large urban areas from the analysis showed an even more pronounced advance of budburst, confirming that the urban 'heat-island' effect is not the sole cause of earlier urban budburst. Similarly, the advance in budburst across all sites is too large to be explained by increases in temperature alone. This dramatic advance of budburst illustrates the need for further experimental investigation into the impact of artificial night-time lighting on plant phenology and subsequent species interactions. As light pollution is a growing global phenomenon, the findings of this study are likely to be applicable to a wide range of species interactions across the world. PMID- 27358371 TI - Ocean acidification alters the response of intertidal snails to a key sea star predator. AB - Organism-level effects of ocean acidification (OA) are well recognized. Less understood are OA's consequences for ecological species interactions. Here, we examine a behaviourally mediated predator-prey interaction within the rocky intertidal zone of the temperate eastern Pacific Ocean, using it as a model system to explore OA's capacity to impair invertebrate anti-predator behaviours more broadly. Our system involves the iconic sea star predator, Pisaster ochraceus, that elicits flee responses in numerous gastropod prey. We examine, in particular, the capacity for OA-associated reductions in pH to alter flight behaviours of the black turban snail, Tegula funebralis, an often-abundant and well-studied grazer in the system. We assess interactions between these species at 16 discrete levels of pH, quantifying the full functional response of Tegula under present and near-future OA conditions. Results demonstrate the disruption of snail anti-predator behaviours at low pH, with decreases in the time individuals spend in refuge locations. We also show that fluctuations in pH, including those typical of rock pools inhabited by snails, do not materially change outcomes, implying little capacity for episodically benign pH conditions to aid behavioural recovery. Together, these findings suggest a strong potential for OA to induce cascading community-level shifts within this long-studied ecosystem. PMID- 27358372 TI - Learning to cope: vocal adjustment to urban noise is correlated with prior experience in black-capped chickadees. AB - Urban noise can interfere with avian communication through masking, but birds can reduce this interference by altering their vocalizations. Although several experimental studies indicate that birds can rapidly change their vocalizations in response to sudden increases in ambient noise, none have investigated whether this is a learned response that depends on previous exposure. Black-capped chickadees (Poecile atricapillus) change the frequency of their songs in response to both fluctuating traffic noise and experimental noise. We investigated whether these responses to fluctuating noise depend on familiarity with noise. We confirmed that males in noisy areas sang higher-frequency songs than those in quiet areas, but found that only males in already-noisy territories shifted songs upwards in immediate response to experimental noise. Unexpectedly, males in more quiet territories shifted songs downwards in response to experimental noise. These results suggest that chickadees may require prior experience with fluctuating noise to adjust vocalizations in such a way as to minimize masking. Thus, learning to cope may be an important part of adjusting to acoustic life in the city. PMID- 27358373 TI - The role of coccolithophore calcification in bioengineering their environment. AB - Coccolithophorids are enigmatic plankton that produce calcium carbonate coccoliths, which over geological time have buried atmospheric CO2 into limestone, changing both the atmosphere and geology of the Earth. However, the role of coccoliths for the proliferation of these organisms remains unclear; suggestions include roles in anti-predation, enhanced photosynthesis and sun screening. Here we test the hypothesis that calcification stabilizes the pH of the seawater proximate to the organisms, providing a level of acidification countering the detrimental basification that occurs during net photosynthesis. Such bioengineering provides a more stable pH environment for growth and fits the empirical evidence for changes in rates of calcification under different environmental conditions. Under this scenario, simulations suggest that the optimal production ratio of inorganic to organic particulate C (PIC : POCprod) will be lower (by approx. 20%) with ocean acidification and that overproduction of coccoliths in a future acidified ocean, where pH buffering is weaker, presents a risk to calcifying cells. PMID- 27358374 TI - Ocean acidification alters fish-jellyfish symbiosis. AB - Symbiotic relationships are common in nature, and are important for individual fitness and sustaining species populations. Global change is rapidly altering environmental conditions, but, with the exception of coral-microalgae interactions, we know little of how this will affect symbiotic relationships. We here test how the effects of ocean acidification, from rising anthropogenic CO2 emissions, may alter symbiotic interactions between juvenile fish and their jellyfish hosts. Fishes treated with elevated seawater CO2 concentrations, as forecast for the end of the century on a business-as-usual greenhouse gas emission scenario, were negatively affected in their behaviour. The total time that fish (yellowtail scad) spent close to their jellyfish host in a choice arena where they could see and smell their host was approximately three times shorter under future compared with ambient CO2 conditions. Likewise, the mean number of attempts to associate with jellyfish was almost three times lower in CO2-treated compared with control fish, while only 63% (high CO2) versus 86% (control) of all individuals tested initiated an association at all. By contrast, none of three fish species tested were attracted solely to jellyfish olfactory cues under present-day CO2 conditions, suggesting that the altered fish-jellyfish association is not driven by negative effects of ocean acidification on olfaction. Because shelter is not widely available in the open water column and larvae of many (and often commercially important) pelagic species associate with jellyfish for protection against predators, modification of the fish-jellyfish symbiosis might lead to higher mortality and alter species population dynamics, and potentially have flow-on effects for their fisheries. PMID- 27358375 TI - Highly cytocompatible and flexible three-dimensional graphene/polydimethylsiloxane composite for culture and electrochemical detection of L929 fibroblast cells. AB - Recently, three-dimensional graphene interconnected network has attracted great interest as a scaffold structure for tissue engineering due to its high biocompatibility, high electrical conductivity, high specific surface area and high porosity. However, free-standing three-dimensional graphene exhibits poor flexibility and stability due to ease of disintegration during processing. In this work, three-dimensional graphene is composited with polydimethylsiloxane to improve the structural flexibility and stability by a new simple two-step process comprising dip coating of polydimethylsiloxane on chemical vapor deposited graphene/Ni foam and wet etching of nickel foam. Structural characterizations confirmed an interconnected three-dimensional multi-layer graphene structure with thin polydimethylsiloxane scaffold. The composite was employed as a substrate for culture of L929 fibroblast cells and its cytocompatibility was evaluated by cell viability (Alamar blue assay), reactive oxygen species production and vinculin immunofluorescence imaging. The result revealed that cell viability on three dimensional graphene/polydimethylsiloxane composite increased with increasing culture time and was slightly different from a polystyrene substrate (control). Moreover, cells cultured on three-dimensional graphene/polydimethylsiloxane composite generated less ROS than the control at culture times of 3-6 h. The results of immunofluorescence staining demonstrated that fibroblast cells expressed adhesion protein (vinculin) and adhered well on three-dimensional graphene/polydimethylsiloxane surface. Good cell adhesion could be attributed to suitable surface properties of three-dimensional graphene/polydimethylsiloxane with moderate contact angle and small negative zeta potential in culture solution. The results of electrochemical study by cyclic voltammetry showed that an oxidation current signal with no apparent peak was induced by fibroblast cells and the oxidation current at an oxidation potential of +0.9 V increased linearly with increasing cell number. Therefore, the three-dimensional graphene/polydimethylsiloxane composite exhibits high cytocompatibility and can potentially be used as a conductive substrate for cell-based electrochemical sensing. PMID- 27358377 TI - A tribute to biologics in advanced colorectal cancer treatment. PMID- 27358376 TI - Microsphere-based scaffolds encapsulating chondroitin sulfate or decellularized cartilage. AB - Extracellular matrix materials such as decellularized cartilage (DCC) and chondroitin sulfate (CS) may be attractive chondrogenic materials for cartilage regeneration. The goal of the current study was to investigate the effects of encapsulation of DCC and CS in homogeneous microsphere-based scaffolds, and to test the hypothesis that encapsulation of these extracellular matrix materials would induce chondrogenesis of rat bone marrow stromal cells. Four different types of homogeneous scaffolds were fabricated from microspheres of poly(D,L lactic-co-glycolic acid): Blank (poly(D,L-lactic-co-glycolic acid) only; negative control), transforming growth factor-beta3 encapsulated (positive control), DCC encapsulated, and CS encapsulated. These scaffolds were then seeded with rat bone marrow stromal cells and cultured for 6 weeks. The DCC and CS encapsulation altered the morphological features of the microspheres, resulting in higher porosities in these groups. Moreover, the mechanical properties of the scaffolds were impacted due to differences in the degree of sintering, with the CS group exhibiting the highest compressive modulus. Biochemical evidence suggested a mitogenic effect of DCC and CS encapsulation on rat bone marrow stromal cells with the matrix synthesis boosted primarily by the inherently present extracellular matrix components. An important finding was that the cell seeded CS and DCC groups at week 6 had up to an order of magnitude higher glycosaminoglycan contents than their acellular counterparts. Gene expression results indicated a suppressive effect of DCC and CS encapsulation on rat bone marrow stromal cell chondrogenesis with differences in gene expression patterns existing between the DCC and CS groups. Overall, DCC and CS were easily included in microsphere-based scaffolds; however, there is a requirement to further refine their concentrations to achieve the differentiation profiles we seek in vitro. PMID- 27358378 TI - PIK3CA mutations in HER2-positive breast cancer: an ongoing conundrum. PMID- 27358380 TI - Preoperative chemoradiotherapy with cisplatin and docetaxel for stage IIIB non small-cell lung cancer: 10-year follow-up of the SAKK 16/01 trial. PMID- 27358379 TI - Outcome according to KRAS-, NRAS- and BRAF-mutation as well as KRAS mutation variants: pooled analysis of five randomized trials in metastatic colorectal cancer by the AIO colorectal cancer study group. AB - BACKGROUND: To explore the impact of KRAS, NRAS and BRAF mutations as well as KRAS mutation variants in patients with metastatic colorectal cancer (mCRC) receiving first-line therapy. PATIENTS AND METHODS: A total of 1239 patients from five randomized trials (FIRE-1, FIRE-3, AIOKRK0207, AIOKRK0604, RO91) were included into the analysis. Outcome was evaluated by the Kaplan-Meier method, log rank tests and Cox models. RESULTS: In 664 tumors, no mutation was detected, 462 tumors were diagnosed with KRAS-, 39 patients with NRAS- and 74 patients with BRAF-mutation. Mutations in KRAS were associated with inferior progression-free survival (PFS) and overall survival (OS) [multivariate hazard ratio (HR) for PFS: 1.20 (1.02-1.42), P = 0.03; multivariate HR for OS: 1.41 (1.17-1.70), P < 0.001]. BRAF mutation was also associated with inferior PFS [multivariate HR: 2.19 (1.59 3.02), P < 0.001] and OS [multivariate HR: 2.99 (2.10-4.25), P < 0.001]. Among specific KRAS mutation variants, the KRAS G12C-variant (n = 28) correlated with inferior OS compared with unmutated tumors [multivariate HR 2.26 (1.25-4.1), P = 0.001]. A similar trend for OS was seen in the KRAS G13D-variant [n = 71, multivariate HR 1.46 (0.96-2.22), P = 0.10]. More frequent KRAS exon 2 variants like G12D [n = 152, multivariate HR 1.17 (0.86-1.6), P = 0.81] and G12V [n = 92, multivariate HR 1.27 (0.87-1.86), P = 0.57] did not have significant impact on OS. CONCLUSION: Mutations in KRAS and BRAF were associated with inferior PFS and OS of mCRC patients compared with patients with non-mutated tumors. KRAS exon 2 mutation variants were associated with heterogeneous outcome compared with unmutated tumors with KRAS G12C and G13D (trend) being associated with rather poor survival. PMID- 27358381 TI - Long-term significance of urinary neopterin in ovarian cancer: a study by the Austrian Association for Gynecologic Oncology (AGO). AB - BACKGROUND: Neopterin is produced by activated macrophages upon stimulation with interferon-gamma (IFN-gamma) and thus, elevated neopterin concentrations in patients indicate cellular inate immune response. Most studies in patients with malignant diseases found an association between higher neopterin concentrations and reduced survival and impaired prognosis. Nevertheless, neopterin is not a classical tumor marker since it is not produced by the cancer cells themselves. PATIENTS AND METHODS: In a study conducted by the Austrian Gynecologic Oncology Group (AGO) in 114 patients with ovarian cystadenomas and 223 patients with invasive ovarian cancer, patients' urinary neopterin was determined before and after primary therapy. The relevance of neopterin in long-term median follow-up was assessed. RESULTS: Elevated levels (cut-off 250 umol/mol creatinine) were found less frequently in women with benign ovarian cystadenomas (24%) than in patients with malignant disease (58%). After 10 years, only 57% of ovarian cancer patients with elevated urinary neopterin levels survived without disease progression following primary therapy when compared with 86% of women with normal levels (P < 0.001). Along with residual tumor, FIGO stage, age and histological type, neopterin was significantly associated with overall survival (OS) and progression-free survival (PFS). The median PFS was 52 and 12 months and the median OS was 81 and 24 months for patients with normal and elevated neopterin, respectively, P < 0.001. In a multivariate Cox regression analysis, only residual tumor, neopterin and age were independently associated with OS, while only residual tumor was predictive for PFS. Thirty patients with early-stage invasive ovarian cancer (FIGO I and II) were analyzed separately. Of 3 patients with elevated neopterin, 2 died of disease in contrast to 2 out of 27 patients with normal neopterin (P = 0.004). CONCLUSION: In ovarian cancer, the negative impact of elevated urinary neopterin levels indicates a detrimental effect of cancer associated inflammatory reaction. PMID- 27358382 TI - Inclusion of elderly patients in oncology clinical trials. AB - BACKGROUND: Physicians need clinical trials assessing benefits and harms of treatments to avoid under-treatment or over-treatment of elderly patients. The main objectives of this report were to examine how data regarding elderly oncology patients were presented in medical literature; and to assess the evolution of this presentation between two time periods. PATIENTS AND METHODS: All phases I, II and III trials dedicated to the treatment of cancer among elderly patients published between 2001 and 2004 and between 2011 and 2014 were reviewed. All phase III clinical trials assessing cancer treatments among adults in the same periods were also reviewed to evaluate potential subgroup analyses in elderly patients in these studies. Key characteristics of interest were extracted by two investigators before descriptive and comparative analyses were undertaken. RESULTS: A total of 1084 trials were included: 366 and 718 from the first and second time period, respectively. Twenty-seven and 193 of these trials were phase I and II trials dedicated to elderly or frail patients, respectively. A large proportion of phase III trials published between 2011 and 2014 reported at least one analysis dedicated to elderly patients (46.7%) versus 19.3% during the first time period. The use of subgroup analyses of elderly patients in phase III trials was the most frequent source of information. Subgroup analyses were more frequent among trials with industrial funding, trials published in high impact factor journal, intercontinental trials and trials with large sample size. The age threshold defining the elderly subgroup increased over time. CONCLUSION: Elderly patients have become a topic of interest during the past decade. However, data available are mostly extracted from subgroup analyses, which can only be regarded as preliminary evidence. PMID- 27358384 TI - Prognostic pathways in early-stage ovarian cancer: can gene expression transcend histological subtype? PMID- 27358383 TI - Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer progressing on prior non-steroidal aromatase inhibitors: primary results of a phase IIIb, open-label, single-arm, expanded-access multicenter trial (BALLET). AB - BACKGROUND: This European phase IIIb, expanded-access multicenter trial evaluated the safety of EVE plus EXE in a patient population similar to BOLERO-2. PATIENTS AND METHODS: Post-menopausal women aged >=18 years with hormone receptor positive, human epidermal growth factor-receptor-2-negative advanced breast cancer (ABC) recurring/progressing during/after prior non-steroidal aromatase inhibitors were enrolled. The primary objective was safety of EVE plus EXE based on frequency of adverse events (AEs), and serious AEs (SAEs). The secondary objective was to evaluate AEs of grade 3/4 severity. RESULTS: The median treatment duration was 5.1 months [95% confidence interval (CI) 4.8-5.6] for EVE and 5.3 months (95% CI 4.8-5.6) for EXE. Overall, 2131 patients were included in the analysis; 81.8% of patients experienced EVE- or EXE-related or EVE/EXE related AEs (investigator assessed); 27.2% were of grade 3/4 severity. The most frequently reported non-hematologic AEs were (overall %, % EVE-related) stomatitis (52.8%; 50.8%) and asthenia (22.8%; 14.6%). The most frequently reported hematologic AEs were (overall %, % EVE-related) anemia (14.4%; 8.1%) and thrombocytopenia (5.9%; 4.6%). AE-related treatment discontinuations were higher in elderly (>=70 years) versus non-elderly patients (23.8% versus 13.0%). The incidence of EVE-related AEs in both elderly and non-elderly patients appeared to be lower in first-line ABC versus later lines. The incidence of AEs (including stomatitis/pneumonitis) was independent of BMI status (post hoc analysis). Overall, 8.5% of patients experienced at least one EVE-related SAE. Of the 121 on treatment deaths (5.7%), 66 (3.1%) deaths were due to disease progression and 46 (2.2%) due to AEs; 4 deaths were suspected to be EVE-related. CONCLUSIONS: This is the largest ever reported safety dataset on a general patient population presenting ABC treated with EVE plus EXE and included a sizeable elderly subset. Although the patients were more heavily pretreated, the safety profile of EVE plus EXE in BALLET was consistent with BOLERO-2. CLINICAL TRIAL REGISTRATION: EudraCT Number: 2012-000073-23. PMID- 27358386 TI - Ipilimumab-related hypophysitis may precede severe CNS immune attack. PMID- 27358385 TI - Randomized, double-blind, phase III trial of palonosetron versus granisetron in the triplet regimen for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy: TRIPLE study. AB - BACKGROUND: There has been no phase III study of comparing the efficacy of first- and second-generation 5-HT3 receptor antagonists in the triplet regimen with dexamethasone and aprepitant for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy (HEC). PATIENTS AND METHODS: Patients with a malignant solid tumor who would receive HEC containing 50 mg/m(2) or more cisplatin were randomly assigned to either palonosetron (0.75 mg) arm (Arm P) or granisetron (1 mg) arm (Arm G), on day 1, both arms with dexamethasone (12 mg on day 1 and 8 mg on days 2-4) and aprepitant (125 mg on day 1 and 80 mg on days 2-3). The primary end point was complete response (CR; no vomiting/retching and no rescue medication) at the 0-120 h period and secondary end points included complete control (CC; no vomiting/retching, no rescue medication, and no more than mild nausea) and total control (TC; no vomiting/retching, no rescue medication, and no nausea). RESULTS: Between July 2011 and June 2012, 842 patients were enrolled. Of 827 evaluable, 272 of 414 patients (65.7%) in Arm P had a CR at the 0-120 h period when compared with 244 of 413 (59.1%) in Arm G (P = 0.0539). Both arms had the same CR rate of 91.8% at the acute (0-24 h) period, while at the delayed (24-120 h) period, Arm P had a significantly higher CR rate than Arm G (67.2% versus 59.1%; P = 0.0142). In secondary end points, Arm P had significantly higher rates than Arm G at the 0 120 h period (CC rate: 63.8% versus 55.9%, P = 0.0234; TC rate: 47.6% versus 40.7%, P = 0.0369) and delayed periods (CC rate: 65.2% versus 55.9%, P = 0.0053; TC rate: 48.6% versus 41.4%, P = 0.0369). CONCLUSION: The present study did not show the superiority of palonosetron when compared with granisetron in the triplet regimen regarding the primary end point. CLINICAL TRIAL REGISTRY IDENTIFIER: UMIN000004863. PMID- 27358387 TI - Is CA125 useful in monitoring patients with platinum-resistant ovarian cancer? PMID- 27358388 TI - Identification of Novel Inhibitors of the Type I Interferon Induction Pathway Using Cell-Based High-Throughput Screening. AB - Production of type I interferon (IFN) is an essential component of the innate immune response against invading pathogens. However, its production must be tightly regulated to avoid harmful effects. Compounds that modulate the IFN response are potentially valuable for a variety of applications due to IFN's beneficial and detrimental roles. We developed and executed a cell-based high throughput screen (HTS) targeting components that participate in and/or regulate the IRF3 and nuclear factor (NF)-kappaB branches of the IFN induction pathway. The assay detects activation of the IFN induction pathway via an enhanced green fluorescent protein (eGFP) reporter gene under the control of the IFNbeta promoter and was optimized, miniaturized, and demonstrated suitable for HTS as robust Z' factor scores of >0.6 were consistently achieved. A diversity screening set of 15,667 small molecules was assayed and two novel hit compounds validated that specifically inhibit the IFN induction pathway. We demonstrate that one of these compounds acts at or upstream of IRF3 phosphorylation. A second cell-based assay to detect activation of the IFN signaling (Jak-Stat) pathway via an eGFP reporter gene under the control of an IFN-stimulated response element (ISRE) containing MxA promoter also performed well (robust Z' factor >0.7) and may therefore be similarly used to identify small molecules that modulate the IFN signaling pathway. PMID- 27358390 TI - Lamin A/C in renal tubular cells is important for tissue repair, cell proliferation, and calcium oxalate crystal adhesion, and is associated with potential crystal receptors. AB - A previous study reported that lamin A/C (LMNA) expression was increased in renal tubular cells adhered with calcium oxalate monohydrate (COM) crystals; however, its functional significance in kidney stone disease remained unknown. In the present study, increased levels of LMNA and its partner, nesprin-1 (SYNE1), in Madin-Darby canine kidney cells upon COM crystal adhesion were confirmed by Western blotting and immunofluorescence staining. LMNA was then knocked down by small interfering RNA. Immunofluorescence staining confirmed the efficiency of small interfering RNA of LMNA (si-LMNA), which also reduced expression of its partner, SYNE1. Scratch assay and total cell count revealed defects in tissue repair and cell proliferation, respectively, whereas cell death quantitation showed no cytotoxicity in si-LMNA-transfected cells. Crystal-binding assay highlighted the role of LMNA in crystal adhesion, whereas protein network analysis revealed interactions between LMNA and potential COM crystal receptors. Their associations were confirmed by reduced levels of these proteins, including vimentin, tubulin, enolase, S100, and annexin A2, in si-LMNA-transfected cells. These data have demonstrated for the first time, to our knowledge, that LMNA in renal tubular cells is important for tissue repair, cell proliferation, and COM crystal adhesion and is associated with potential COM crystal receptors. Therefore, LMNA may serve as a potential target for prevention of kidney stone disease and its recurrence.-Pongsakul, N., Vinaiphat, A., Chanchaem, P., Fong ngern, K., Thongboonkerd, V. Lamin A/C in renal tubular cells is important for tissue repair, cell proliferation, and calcium oxalate crystal adhesion, and is associated with potential crystal receptors. PMID- 27358389 TI - ERK1/2 activation in human taste bud cells regulates fatty acid signaling and gustatory perception of fat in mice and humans. AB - Obesity is a major public health problem. An in-depth knowledge of the molecular mechanisms of oro-sensory detection of dietary lipids may help fight it. Humans and rodents can detect fatty acids via lipido-receptors, such as CD36 and GPR120. We studied the implication of the MAPK pathways, in particular, ERK1/2, in the gustatory detection of fatty acids. Linoleic acid, a dietary fatty acid, induced via CD36 the phosphorylation of MEK1/2-ERK1/2-ETS-like transcription factor-1 cascade, which requires Fyn-Src kinase and lipid rafts in human taste bud cells (TBCs). ERK1/2 cascade was activated by Ca2+ signaling via opening of the calcium homeostasis modulator-1 (CALHM1) channel. Furthermore, fatty acid-evoked Ca2+ signaling and ERK1/2 phosphorylation were decreased in both human TBCs after small interfering RNA knockdown of CALHM1 channel and in TBCs from Calhm1-/- mice. Targeted knockdown of ERK1/2 by small interfering RNA or PD0325901 (MEK1/2 inhibitor) in the tongue and genetic ablation of Erk1 or Calhm1 genes impaired preference for dietary fat in mice. Lingual inhibition of ERK1/2 in healthy volunteers also decreased orogustatory sensitivity for linoleic acid. Our data demonstrate that ERK1/2-MAPK cascade is regulated by the opening of CALHM1 Ca2+ channel in TBCs to modulate orogustatory detection of dietary lipids in mice and humans.-Subramaniam, S., Ozdener, M. H., Abdoul-Azize, S., Saito, K., Malik, B., Maquart, G., Hashimoto, T., Marambaud, P., Aribi, M., Tordoff, M. G., Besnard, P., Khan, N. A. ERK1/2 activation in human taste bud cells regulates fatty acid signaling and gustatory perception of fat in mice and humans. PMID- 27358391 TI - Highly conserved epigenetic regulation of BOULE and DAZL is associated with human fertility. AB - Separation of germ cells from somatic cells is a widespread feature of animal sexual reproduction, with a core set of germ cell factors conserved among diverse animals. It is not known what controls their conserved gonad-specific expression. Core components of epigenetic machinery are ancient, but its role in conserved tissue expression regulation remains unexplored. We found that promoters of the reproductive genes BOULE and DAZL exhibit differential DNA methylation, consistent with their gonad-specific expression in humans and mice. Low or little promoter methylation from the testicular tissue is attributed to spermatogenic cells of various stages in the testis. Such differential DNA methylation is present in the orthologous promoters not only of other mammalian species, but also of chickens and fish, supporting a highly conserved epigenetic mechanism. Furthermore, hypermethylation of DAZL and BOULE promoters in human sperm is associated with human infertility. Our data strongly suggest that epigenetic regulation may underlie conserved germ-cell-specific expression, and such a mechanism may play an important role in human fertility.-Zhang, C., Xue, P., Gao, L., Chen, X., Lin, K., Yang, X., Dai, Y., Xu, E. Y. Highly conserved epigenetic regulation of BOULE and DAZL is associated with human fertility. PMID- 27358394 TI - Effect of energy-efficient measures in building construction on indoor radon in Russia. AB - The effect of implementation of energy-efficient measures in building construction was studied. Analysis includes study of indoor radon in energy efficient buildings in Ekaterinburg, Russia, and results of radiation measurements in 83 regions of Russia conducted within the regional programmes. The forecast distribution of radon concentration in Ekaterinburg was built with regard to the city development programme. With Ekaterinburg taken as representative case, forecast distribution of radon concentration in Russia in 2030 was built. In comparison with 2000, average radon concentration increases by a factor of 1.42 in 2030 year; percentage above the reference level 300 Bq/m3 increases by a factor of 4 in 2030 year. It is necessary to perceive such an increase with all seriousness and to prepare appropriate measures for optimization of protection against indoor radon. Despite the high uncertainty, reconstructed distribution of radon concentration can be applied for justification of measures to be incorporated in the radon mitigation strategy. PMID- 27358392 TI - Lesional CD4+ IFN-gamma+ cytotoxic T lymphocytes in IgG4-related dacryoadenitis and sialoadenitis. AB - OBJECTIVES: IgG4-related disease (IgG4-RD) is a chronic, systemic, inflammatory condition of unknown aetiology. We have recently described clonally expanded circulating CD4+ cytotoxic T lymphocytes (CTLs) in IgG4-RD that infiltrate affected tissues where they secrete interleukin (IL)-1beta and transforming growth factor -beta1 (TGF-beta1). In this study, we sought to examine the role of CD4+ CTLs in the pathogenesis of IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) and to determine whether these cells secrete interferon-gamma (IFN gamma) at lesional sites. METHODS: Salivary glands of 25 patients with IgG4-DS, 22 patients with Sjogren's syndrome (SS), 12 patients with chronic sialoadenitis (CS) and 12 healthy controls were analysed in this study. Gene expression analysis was performed on submandibular glands (SMGs) from five patients with IgG4-DS, three with CS and three healthy controls. Infiltrating CD4+ CTLs were examined by quantitative multicolour imaging in tissue samples from 20 patients with IgG4-DS, 22 patients with SS, 9 patients with CS and 9 healthy controls. RESULTS: In IgG4-DS tissues, nine genes associated with CD4+ CTLs were overexpressed. The expression of granzyme A (GZMA) mRNA was significantly higher in samples from patients with IgG4-RD compared with corresponding tissues from SS and healthy controls. Quantitative imaging showed that infiltrating CD4+ GZMA+ CTLs were more abundant in patients with IgG4-DS than in the other groups. The ratio of CD4+GZMA+ CTLs in SMGs from patients with IgG4-DS correlated with serum IgG4 concentrations and the number of affected organs. A large fraction of CD4+GZMA+ CTLs in SMGs from patients with IgG4-DS secreted IFN-gamma. CONCLUSIONS: The pathogenesis of IgG4-DS is associated with tissue infiltration by CD4+GZMA+ CTLs that secrete IFN-gamma. PMID- 27358395 TI - First National Conference on Radiation Awareness and Detection in Natural Environment, Tehri Garhwal, India, June 15-17, 2015. PMID- 27358393 TI - Millions of reads, thousands of taxa: microbial community structure and associations analyzed via marker genes. AB - With high-throughput sequencing (HTS), we are able to explore the hidden world of microscopic organisms to an unpre-cedented level. The fast development of molecular technology and statistical methods means that microbial ecologists must keep their toolkits updated. Here, we review and evaluate some of the more widely adopted and emerging techniques for analysis of diversity and community composition, and the inference of species interactions from co-occurrence data generated by HTS of marker genes. We emphasize the importance of observational biases and statistical properties of the data and methods. The aim of the review is to critically discuss the advantages and disadvantages of established and emerging statistical methods, and to contribute to the integration of HTS-based marker gene data into community ecology. PMID- 27358396 TI - The Project Of Another Low-Cost Metaphase Finder. AB - The most popular and 'gold standard' phenomenon in Biological dosimetry is the appearance of dicentric chromosomes in metaphase in white blood cells. The metaphase finder is a tool for biological dosimetry that finds metaphase cells on slide glasses. The author and a software company were using new special software that was faster than conventional systems. A Nikon Eclipse Ni-E microscope with motorised X-Y stage, 4* objective lens and 1920 * 1024 pixels colour camera for hardware were used. The software uses mathematical morphology filters. The new system was compact and low-priced. And the remarkable point is, this system can be applicable not only to human blood, but also to non-human samples. The speed was 208-236 s per 5 * 20 mm area, while capturing 378 images, which achieved the aim of the project. The false-positive ratio achieved below 5% in some slides. PMID- 27358397 TI - Role of Spinophilin in Group I Metabotropic Glutamate Receptor Endocytosis, Signaling, and Synaptic Plasticity. AB - Activation of Group I metabotropic glutamate receptors (mGluRs) activates signaling cascades, resulting in calcium release from intracellular stores, ERK1/2 activation, and long term changes in synaptic activity that are implicated in learning, memory, and neurodegenerative diseases. As such, elucidating the molecular mechanisms underlying Group I mGluR signaling is important for understanding physiological responses initiated by the activation of these receptors. In the current study, we identify the multifunctional scaffolding protein spinophilin as a novel Group I mGluR-interacting protein. We demonstrate that spinophilin interacts with the C-terminal tail and second intracellular loop of Group I mGluRs. Furthermore, we show that interaction of spinophilin with Group I mGluRs attenuates receptor endocytosis and phosphorylation of ERK1/2, an effect that is dependent upon the interaction of spinophilin with the C-terminal PDZ binding motif encoded by Group I mGluRs. Spinophilin knock-out results in enhanced mGluR5 endocytosis as well as increased ERK1/2, AKT, and Ca(2+) signaling in primary cortical neurons. In addition, the loss of spinophilin expression results in impaired mGluR5-stimulated LTD. Our results indicate that spinophilin plays an important role in regulating the activity of Group I mGluRs as well as their influence on synaptic activity. PMID- 27358398 TI - Upstream Open Reading Frames Differentially Regulate Gene-specific Translation in the Integrated Stress Response. AB - Translation regulation largely occurs during initiation, which features ribosome assembly onto mRNAs and selection of the translation start site. Short, upstream ORFs (uORFs) located in the 5'-leader of the mRNA can be selected for translation. Multiple transcripts associated with stress amelioration are preferentially translated through uORF-mediated mechanisms during activation of the integrated stress response (ISR) in which phosphorylation of the alpha subunit of eIF2 results in a coincident global reduction in translation initiation. This review presents key features of uORFs that serve to optimize translational control that is essential for regulation of cell fate in response to environmental stresses. PMID- 27358399 TI - Photosystem II Subunit PsbS Is Involved in the Induction of LHCSR Protein dependent Energy Dissipation in Chlamydomonas reinhardtii. AB - Non-photochemical quenching of excess excitation energy is an important photoprotective mechanism in photosynthetic organisms. In Arabidopsis thaliana, a high quenching capacity is constitutively present and depends on the PsbS protein. In the green alga Chlamydomonas reinhardtii, non-photochemical quenching becomes activated upon high light acclimation and requires the accumulation of light harvesting complex stress-related (LHCSR) proteins. Expression of the PsbS protein in C. reinhardtii has not been reported yet. Here, we show that PsbS is a light-induced protein in C. reinhardtii, whose accumulation under high light is further controlled by CO2 availability. PsbS accumulated after several hours of high light illumination at low CO2 At high CO2, however, PsbS was only transiently expressed under high light and was degraded after 1 h of high light exposure. PsbS accumulation correlated with an enhanced non-photochemical quenching capacity in high light-acclimated cells grown at low CO2 However, PsbS could not compensate for the function of LHCSR in an LHCSR-deficient mutant. Knockdown of PsbS accumulation led to reduction of both non-photochemical quenching capacity and LHCSR3 accumulation. Our data suggest that PsbS is essential for the activation of non-photochemical quenching in C. reinhardtii, possibly by promoting conformational changes required for activation of LHCSR3 dependent quenching in the antenna of photosystem II. PMID- 27358400 TI - Functional Similarities between the Protein O-Mannosyltransferases Pmt4 from Bakers' Yeast and Human POMT1. AB - Protein O-mannosylation is an essential post-translational modification. It is initiated in the endoplasmic reticulum by a family of protein O mannosyltransferases that are conserved from yeast (PMTs) to human (POMTs). The degree of functional conservation between yeast and human protein O mannosyltransferases is uncharacterized. In bakers' yeast, the main in vivo activities are due to heteromeric Pmt1-Pmt2 and homomeric Pmt4 complexes. Here we describe an enzymatic assay that allowed us to monitor Pmt4 activity in vitro We demonstrate that detergent requirements and acceptor substrates of yeast Pmt4 are different from Pmt1-Pmt2, but resemble that of human POMTs. Furthermore, we mimicked two POMT1 amino acid exchanges (G76R and V428D) that result in severe congenital muscular dystrophies in humans, in yeast Pmt4 (I112R and I435D). In vivo and in vitro analyses showed that general features such as protein stability of the Pmt4 variants were not significantly affected, however, the mutants proved largely enzymatically inactive. Our results demonstrate functional and biochemical similarities between POMT1 and its orthologue from bakers' yeast Pmt4. PMID- 27358401 TI - Dectin-2 Recognizes Mannosylated O-antigens of Human Opportunistic Pathogens and Augments Lipopolysaccharide Activation of Myeloid Cells. AB - LPS consists of a relatively conserved region of lipid A and core oligosaccharide and a highly variable region of O-antigen polysaccharide. Whereas lipid A is known to bind to the Toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex, the role of the O-antigen remains unclear. Here we report a novel molecular interaction between dendritic cell-associated C-type lectin-2 (Dectin 2) and mannosylated O-antigen found in a human opportunistic pathogen, Hafnia alvei PCM 1223, which has a repeating unit of [-Man-alpha1,3-Man-alpha1,2-Man alpha1,2-Man-alpha1,2-Man-alpha1,3-]. H. alvei LPS induced higher levels of TNFalpha and IL-10 from mouse bone marrow-derived dendritic cells (BM-DCs), when compared with Salmonella enterica O66 LPS, which has a repeat of [-Gal-alpha1,6 Gal-alpha1,4-[Glc-beta1,3]GalNAc-alpha1,3-GalNAc-beta1,3-]. In a cell-based reporter assay, Dectin-2 was shown to recognize H. alvei LPS. This binding was inhibited by mannosidase treatment of H. alvei LPS and by mutations in the carbohydrate-binding domain of Dectin-2, demonstrating that H. alvei LPS is a novel glycan ligand of Dectin-2. The enhanced cytokine production by H. alvei LPS was Dectin-2-dependent, because Dectin-2 knock-out BM-DCs failed to do so. This receptor cross-talk between Dectin-2 and TLR4 involved events including spleen tyrosine kinase (Syk) activation and receptor juxtaposition. Furthermore, another mannosylated LPS from Escherichia coli O9a also bound to Dectin-2 and augmented TLR4 activation of BM-DCs. Taken together, these data indicate that mannosylated O-antigens from several Gram-negative bacteria augment TLR4 responses through interaction with Dectin-2. PMID- 27358402 TI - PtdIns(3,4,5)P3-dependent Rac Exchanger 1 (PREX1) Rac-Guanine Nucleotide Exchange Factor (GEF) Activity Promotes Breast Cancer Cell Proliferation and Tumor Growth via Activation of Extracellular Signal-regulated Kinase 1/2 (ERK1/2) Signaling. AB - PtdIns(3,4,5)P3-dependent Rac exchanger 1 (PREX1) is a Rac-guanine nucleotide exchange factor (GEF) overexpressed in a significant proportion of human breast cancers that integrates signals from upstream ErbB2/3 and CXCR4 membrane surface receptors. However, the PREX1 domains that facilitate its oncogenic activity and downstream signaling are not completely understood. We identify that ERK1/2 MAPK acts downstream of PREX1 and contributes to PREX1-mediated anchorage-independent cell growth. PREX1 overexpression increased but its shRNA knockdown decreased ERK1/2 phosphorylation in response to EGF/IGF-1 stimulation, resulting in induction of the cell cycle regulators cyclin D1 and p21(WAF1/CIP1) PREX1 mediated ERK1/2 phosphorylation, anchorage-independent cell growth, and cell migration were suppressed by inhibition of MEK1/2/ERK1/2 signaling. PREX1 overexpression reduced staurosporine-induced apoptosis whereas its shRNA knockdown promoted apoptosis in response to staurosporine or the anti-estrogen drug tamoxifen. Expression of wild-type but not GEF-inactive PREX1 increased anchorage-independent cell growth. In addition, mouse xenograft studies revealed that expression of wild-type but not GEF-dead PREX1 resulted in the formation of larger tumors that displayed increased phosphorylation of ERK1/2 but not AKT. The impaired anchorage-independent cell growth, apoptosis, and ERK1/2 signaling observed in stable PREX1 knockdown cells was restored by expression of wild-type but not GEF-dead-PREX1. Therefore, PREX1-Rac-GEF activity is critical for PREX1 dependent anchorage-independent cell growth and xenograft tumor growth and may represent a possible therapeutic target for breast cancers that exhibit PREX1 overexpression. PMID- 27358403 TI - Complex Formation of Human Proelastases with Procarboxypeptidases A1 and A2. AB - The pancreas secretes digestive proenzymes typically in their monomeric form. A notable exception is the ternary complex formed by proproteinase E, chymotrypsinogen C, and procarboxypeptidase A (proCPA) in cattle and other ruminants. In the human and pig pancreas binary complexes of proCPA with proelastases were found. To characterize complex formation among human pancreatic protease zymogens in a systematic manner, we performed binding experiments using recombinant proelastases CELA2A, CELA3A, and CELA3B; chymotrypsinogens CTRB1, CTRB2, CTRC, and CTRL1; and procarboxypeptidases CPA1, CPA2, and CPB1. We found that proCELA3B bound not only to proCPA1 (KD 43 nm) but even more tightly to proCPA2 (KD 18 nm), whereas proCELA2A bound weakly to proCPA1 only (KD 152 nm). Surprisingly, proCELA3A, which shares 92% identity with proCELA3B, did not form stable complexes due to the evolutionary replacement of Ala(241) with Gly. The polymorphic nature of position 241 in both CELA3A (~4% Ala(241) alleles) and CELA3B (~2% Gly(241) alleles) points to individual variations in complex formation. The functional effect of complex formation was delayed procarboxypeptidase activation due to increased affinity of the inhibitory activation peptide, whereas proelastase activation was unchanged. We conclude that complex formation among human pancreatic protease zymogens is limited to a subset of proelastases and procarboxypeptidases. Complex formation stabilizes the inhibitory activation peptide of procarboxypeptidases and thereby increases zymogen stability and controls activation. PMID- 27358404 TI - Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4. AB - Skeletal muscle atrophy is a serious and highly prevalent condition that remains poorly understood at the molecular level. Previous work found that skeletal muscle atrophy involves an increase in skeletal muscle Gadd45a expression, which is necessary and sufficient for skeletal muscle fiber atrophy. However, the direct mechanism by which Gadd45a promotes skeletal muscle atrophy was unknown. To address this question, we biochemically isolated skeletal muscle proteins that associate with Gadd45a as it induces atrophy in mouse skeletal muscle fibers in vivo We found that Gadd45a interacts with multiple proteins in skeletal muscle fibers, including, most prominently, MEKK4, a mitogen-activated protein kinase kinase kinase that was not previously known to play a role in skeletal muscle atrophy. Furthermore, we found that, by forming a complex with MEKK4 in skeletal muscle fibers, Gadd45a increases MEKK4 protein kinase activity, which is both sufficient to induce skeletal muscle fiber atrophy and required for Gadd45a mediated skeletal muscle fiber atrophy. Together, these results identify a direct biochemical mechanism by which Gadd45a induces skeletal muscle atrophy and provide new insight into the way that skeletal muscle atrophy occurs at the molecular level. PMID- 27358405 TI - Epitope Mapping of Rhi o 1 and Generation of a Hypoallergenic Variant: A CANDIDATE MOLECULE FOR FUNGAL ALLERGY VACCINES. AB - Efficacy of allergen-specific immunotherapy is often severely impaired by detrimental IgE-mediated side effects of native allergen during vaccination. Here, we present the molecular determinants for IgE recognition of Rhi o 1 and eventually converting the allergen into a hypoallergenic immunogen to restrain health hazards during desensitization. Rhi o 1 is a respiratory fungal allergen. Despite having cross-reactivity with cockroach allergen, we observed that non cross-reactive epitope predominantly determined IgE binding to Rhi o 1. Denaturation and refolding behavior of the allergen confirmed that its IgE reactivity was not essentially conformation-dependent. A combinatorial approach consisting of computational prediction and a peptide-based immunoassay identified two peptides ((44)TGEYLTQKYFNSQRNN and (311)GAEKNWAGQYVVDCNK) of Rhi o 1 that frequently reacted with IgE antibodies of sensitized patients. Interestingly, these peptides did not represent purely linear IgE epitopes but were presented in a conformational manner by forming a spatially clustered surface-exposed epitope conferring optimal IgE-binding capacity to the folded allergen. Site-directed alanine substitution identified four residues of the IgE epitope that were crucial for antibody binding. A multiple mutant (T49A/Y52A/K314A/W316A) showing 100-fold lower IgE binding and reduced allergenic activity was generated. The TYKW mutant retained T-cell epitopes, as evident from its lymphoproliferative capacity but down-regulated pro-allergic IL-5 secretion. The TYKW mutant induced enhanced focusing of blocking IgG antibodies specifically toward the IgE epitope of the allergen. Anti-TYKW mutant polyclonal IgG antibodies competitively inhibited binding of IgE antibodies to Rhi o 1 up to 70% and suppressed allergen mediated histamine release by 10-fold. In conclusion, this is a simple yet rational strategy based on epitope mapping data to develop a genetically modified hypoallergenic variant showing protective antibody response for immunotherapeutic applications. PMID- 27358406 TI - Inhibition of Macrophage CD36 Expression and Cellular Oxidized Low Density Lipoprotein (oxLDL) Accumulation by Tamoxifen: A PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR (PPAR)gamma-DEPENDENT MECHANISM. AB - Macrophage CD36 binds and internalizes oxidized low density lipoprotein (oxLDL) to facilitate foam cell formation. CD36 expression is activated by peroxisome proliferator-activated receptor gamma (PPARgamma). Tamoxifen, an anti-breast cancer medicine, has demonstrated pleiotropic functions including cardioprotection with unfully elucidated mechanisms. In this study, we determined that treatment of ApoE-deficient mice with tamoxifen reduced atherosclerosis, which was associated with decreased CD36 and PPARgamma expression in lesion areas. At the cellular level, we observed that tamoxifen inhibited CD36 protein expression in human THP-1 monocytes, THP-1/PMA macrophages, and human blood monocyte-derived macrophages. Associated with decreased CD36 protein expression, tamoxifen reduced cellular oxLDL accumulation in a CD36-dependent manner. At the transcriptional level, tamoxifen decreased CD36 mRNA expression, promoter activity, and the binding of the PPARgamma response element in CD36 promoter to PPARgamma protein. Tamoxifen blocked ligand-induced PPARgamma nuclear translocation and CD36 expression, but it increased PPARgamma phosphorylation, which was due to that tamoxifen-activated ERK1/2. Furthermore, deficiency of PPARgamma expression in macrophages abolished the inhibitory effect of tamoxifen on CD36 expression or cellular oxLDL accumulation both in vitro and in vivo Taken together, our study demonstrates that tamoxifen inhibits CD36 expression and cellular oxLDL accumulation by inactivating the PPARgamma signaling pathway, and the inhibition of macrophage CD36 expression can be attributed to the anti atherogenic properties of tamoxifen. PMID- 27358407 TI - Starch Binding Domain-containing Protein 1 Plays a Dominant Role in Glycogen Transport to Lysosomes in Liver. AB - A small portion of cellular glycogen is transported to and degraded in lysosomes by acid alpha-glucosidase (GAA) in mammals, but it is unclear why and how glycogen is transported to the lysosomes. Stbd1 has recently been proposed to participate in glycogen trafficking to lysosomes. However, our previous study demonstrated that knockdown of Stbd1 in GAA knock-out mice did not alter lysosomal glycogen storage in skeletal muscles. To further determine whether Stbd1 participates in glycogen transport to lysosomes, we generated GAA/Stbd1 double knock-out mice. In fasted double knock-out mice, glycogen accumulation in skeletal and cardiac muscles was not affected, but glycogen content in liver was reduced by nearly 73% at 3 months of age and by 60% at 13 months as compared with GAA knock-out mice, indicating that the transport of glycogen to lysosomes was suppressed in liver by the loss of Stbd1. Exogenous expression of human Stbd1 in double knock-out mice restored the liver lysosomal glycogen content to the level of GAA knock-out mice, as did a mutant lacking the Atg8 family interacting motif (AIM) and another mutant that contains only the N-terminal 24 hydrophobic segment and the C-terminal starch binding domain (CBM20) interlinked by an HA tag. Our results demonstrate that Stbd1 plays a dominant role in glycogen transport to lysosomes in liver and that the N-terminal transmembrane region and the C terminal CBM20 domain are critical for this function. PMID- 27358408 TI - JunD Is Required for Proliferation of Prostate Cancer Cells and Plays a Role in Transforming Growth Factor-beta (TGF-beta)-induced Inhibition of Cell Proliferation. AB - TGF-beta inhibits proliferation of prostate epithelial cells. However, prostate cancer cells in advanced stages become resistant to inhibitory effects of TGF beta. The intracellular signaling mechanisms involved in differential effects of TGF-beta during different stages are largely unknown. Using cell line models, we have shown that TGF-beta inhibits proliferation in normal (RWPE-1) and prostate cancer (DU145) cells but does not have any effect on proliferation of prostate cancer (PC3) cells. We have investigated the role of Jun family proteins (c-Jun, JunB, and JunD) in TGF-beta effects on cell proliferation. Jun family members were expressed at different levels and responded differentially to TGF-beta treatment. TGF-beta effects on JunD protein levels, but not mRNA levels, correlated with its effects on cell proliferation. TGF-beta induced significant reduction in JunD protein in RWPE-1 and DU145 cells but not in PC3 cells. Selective knockdown of JunD expression using siRNA in DU145 and PC3 cells resulted in significant reduction in cell proliferation, and forced overexpression of JunD increased the proliferation rate. On the other hand, knockdown of c-Jun or JunB had little, if any, effect on cell proliferation; overexpression of c-Jun and JunB decreased the proliferation rate in DU145 cells. Further studies showed that down-regulation of JunD in response to TGF-beta treatment is mediated via the proteasomal degradation pathway. In conclusion, we show that specific Jun family members exert differential effects on proliferation in prostate cancer cells in response to TGF-beta, and inhibition of cell proliferation by TGF-beta requires degradation of JunD protein. PMID- 27358409 TI - Heme-independent Redox Sensing by the Heme-Nitric Oxide/Oxygen-binding Protein (H NOX) from Vibrio cholerae. AB - Heme nitric oxide/oxygen (H-NOX)-binding proteins act as nitric oxide (NO) sensors among various bacterial species. In several cases, they act to mediate communal behavior such as biofilm formation, quorum sensing, and motility by influencing the activity of downstream signaling proteins such as histidine kinases (HisKa) in a NO-dependent manner. An H-NOX/HisKa regulatory circuit was recently identified in Vibrio cholerae, and the H-NOX protein has been spectroscopically characterized. However, the influence of the H-NOX protein on HisKa autophosphorylation has not been evaluated. This process may be important for persistence and pathogenicity in this organism. Here, we have expressed and purified the V. cholerae HisKa (HnoK) and H-NOX in its heme-bound (holo) and heme free (apo) forms. Autophosphorylation assays of HnoK in the presence of H-NOX show that the holoprotein in the Fe(II)-NO and Fe(III) forms is a potent inhibitor of HnoK. Activity of the Fe(III) form and aerobic instability of the Fe(II) form suggested that Vibrio cholerae H-NOX may act as a sensor of the redox state as well as NO. Remarkably, the apoprotein also showed robust HnoK inhibition that was dependent on the oxidation of cysteine residues to form disulfide bonds at a highly conserved zinc site. The importance of cysteine in this process was confirmed by mutagenesis, which also showed that holo Fe(III), but not Fe(II)-NO, H-NOX relied heavily upon cysteine for activation. These results highlight a heme-independent mechanism for activation of V. cholerae H NOX that implicates this protein as a dual redox/NO sensor. PMID- 27358410 TI - Antibiotics for tonsillitis: should the emergency department emulate general practice? AB - OBJECTIVES: To determine whether antibiotics are prescribed appropriately for acute tonsillitis in an emergency department (ED). METHODS: Cross-sectional observational study in large district general hospital in London. Patients diagnosed and coded with 'acute tonsillitis' in the ED over a 3-month period in 2015. Medical records were reviewed for Centor criteria, which is a clinical scoring system to guide antibiotic prescribing in UK general practice. Drug charts were reviewed for the specific antibiotic(s) prescribed, and throat swab (TS) cultures were recorded. RESULTS: 273/389 patients with tonsillitis were analysed-186 children, 87 adults. Exclusions were missing patient records (86), patients had/awaiting tonsillectomy (22), receiving antibiotics (6) and immunocompromised (2). Centor score (CS) was not recorded for any patient. Based on derived CS from documented signs/symptoms, antibiotics were prescribed inappropriately to 196/273 patients (80%; 95% CI 74% to 85%) including broad spectrum antibiotics to 25%. These included co-amoxiclav (18%), amoxicillin (6%), azithromycin (0.5%) and ceftriaxone (0.5%). TSs were taken in 66/273(24%) patients; 10/66 were positive for group A streptococcus (GAS). However, 48/56 GAS negative patients were prescribed antibiotics. CONCLUSIONS: CS was not being used in the ED to guide antibiotic prescribing for acute tonsillitis. Antibiotic prescribing was based on clinical judgement. Based on derived CS (<3), 80% of patients were inappropriately prescribed antibiotics, particularly broad-spectrum antibiotics. Further studies need to assess use of CS to guide antibiotic prescription in ED. TSs were commonly performed in the ED but did not either improve diagnosis or guide antibiotic prescription. PMID- 27358411 TI - Mango Supplementation Modulates Gut Microbial Dysbiosis and Short-Chain Fatty Acid Production Independent of Body Weight Reduction in C57BL/6 Mice Fed a High Fat Diet. AB - BACKGROUND: High-fat (HF) diet-induced obesity is associated with changes in the gut microbiota. Fiber and other bioactive compounds in plant-based foods are suggested to prevent gut dysbiosis brought on by HF feeding. Mango is high in fiber and has been reported to have anti-obesogenic, hypoglycemic, and immunomodulatory properties. OBJECTIVES: We investigated the effects of freeze dried mango pulp combined with an HF diet on the cecal microbial population and its relation to body composition, lipids, glucose parameters, short-chain fatty acid (SCFA) production, and gut inflammatory markers in a mouse model of diet induced obesity. METHODS: Six-wk-old male C57BL/6 mice were randomly assigned to 1 of 4 dietary treatment groups: control (AIN-93M, 10% fat kcal), HF (60% fat kcal), and HF + 1% or 10% mango (HF+1%M or HF+10%M, wt:wt) for 12 wk. The cecal microbial population was assessed by use of 16S rDNA sequencing. Body composition, plasma glucose and lipids, cecal and fecal SCFAs, and mRNA abundance of inflammatory markers in the ileum and colonic lamina propria were assessed. RESULTS: Compared with the control group, HF feeding significantly reduced (P < 0.05) 1 operational taxonomic unit (OTU) of the genus Bifidobacteria (64-fold) and 5 OTUs of the genus Akkermansia (>=16-fold). This reduction was prevented in the HF+10%M group, members of which had 10% higher final body weight compared with the HF group (P = 0.01) and similar fasting blood glucose concentrations (P = 0.24). The HF+10%M group had 135% (P = 0.004) and 133% (P < 0.0001) greater fecal acetic and n-butyric acids concentrations than the HF group, suggesting greater microbial fermentation. Furthermore, a 59% greater colonic interleukin 10 (Il10) gene expression was observed in the HF+10%M group than in the HF group (P = 0.048), indicating modulation of gut inflammation. The HF+1%M group generally did not differ from the HF group. CONCLUSIONS: The addition of mango to an HF diet modulated the gut microbiota and production of SCFAs in C57BL/6 mice; these changes may improve gut tolerance to the insult of an HF diet. PMID- 27358412 TI - Salmosan, a beta-Galactomannan-Rich Product, Protects Epithelial Barrier Function in Caco-2 Cells Infected by Salmonella enterica Serovar Enteritidis. AB - BACKGROUND: One promising strategy for reducing human salmonellosis induced by Salmonella Enteritidis is to supplement animal diets with natural feed additives such as mannan oligosaccharides (MOSs). OBJECTIVE: We sought to investigate the potential role of Salmosan (S-betaGM), an MOS product extremely rich in beta galactomannan, in preventing epithelial barrier function disruption induced by S. Enteritidis colonization in an in vitro model of intestinal Caco-2 cells in culture. METHODS: Differentiated Caco-2 cells were incubated for 3 h with S. Enteritidis at a multiplicity of infection of 10 in the absence or presence of 500 MUg S-betaGM/mL. Paracellular permeability (PP) was assessed by transepithelial electrical resistance (TER), d-mannitol, and fluorescein isothiocyanate-dextran (FD-4) flux. Tight junction proteins and cytoskeletal actin were also localized by confocal microscopy. Reactive oxygen species (ROS) and lipid peroxidation products were evaluated. Scanning and transmission electron microscopy were used to visualize S. Enteritidis adhesion to, and invasion of, the Caco-2 cell cultures. RESULTS: Compared with controls, TER was significantly reduced by 30%, and d-mannitol and FD-4 flux were significantly increased by 374% and 54% in S. Enteritidis-infected cultures, respectively. The presence of S-betaGM in infected cultures induced total recoveries of TER and FD 4 flux to values that did not differ from the control and a partial recovery of d mannitol flux. These effects were confirmed by immunolocalization of actin, zonula occludens protein 1, and occludin. Similar results were obtained for Salmonella Dublin. The protection of S-betaGM on PP in infected cultures may be associated with a total recovery of ROS production to values that did not differ from the control. Moreover, S-betaGM has the capacity to agglutinate bacteria, leading to a significant reduction of 32% in intracellular S Enteritidis. CONCLUSION: The results demonstrate that S-betaGM contributes to protecting epithelial barrier function in a Caco-2 cell model disrupted by S. Enteritidis. PMID- 27358413 TI - Frequent Consumption of Sugar- and Artificially Sweetened Beverages and Natural and Bottled Fruit Juices Is Associated with an Increased Risk of Metabolic Syndrome in a Mediterranean Population at High Cardiovascular Disease Risk. AB - BACKGROUND: The relation between the consumption of sweetened beverages and metabolic syndrome (MetS) is controversial. OBJECTIVE: This analysis evaluated the associations between intakes of sugar-sweetened beverages (SSBs), artificially sweetened beverages, and natural and bottled fruit juices and the incidence of MetS in elderly individuals at high risk of cardiovascular disease (CVD) and without MetS at baseline. METHODS: We prospectively examined 1868 participants free of MetS at baseline from the PREDIMED (PREvencion con DIeta MEDiterranea) study. MetS was defined by using the updated harmonized criteria of the International Diabetes Federation, the American Heart Association, and National Heart, Lung, and Blood Institute. Energy and nutrient intakes were evaluated at baseline and then yearly by using a validated 137-item food frequency questionnaire. Multivariable-adjusted HRs for MetS and its components were estimated from mean intakes during follow-up. We compared the 2 highest consumption categories (1-5 and >5 servings/wk) with the lowest category (<1 serving/wk). RESULTS: A total of 930 incident cases of MetS were documented during a median follow-up of 3.24 y. When we compared consumption of >5 servings/wk with consumption of <1 serving/wk, multivariable HRs (95% CIs) for MetS incidence were 1.43 (1.00, 2.15), 1.74 (1.26, 2.41), 1.30 (1.00, 1.69), and 1.14 (1.04, 1.65) for SSBs, artificially sweetened beverages, natural fruit juices, and bottled fruit juices, respectively. CONCLUSIONS: The occasional consumption of SSBs and artificially sweetened beverages (1-5 servings/wk) was not associated with the incidence of MetS in middle-aged and elderly individuals at high risk of CVD. The consumption of >5 servings/wk of all of the types of beverages analyzed was associated with an increased risk of MetS and some of its components. However, for SSBs and bottled fruit juices these associations must be interpreted with caution because of the low frequency of consumption in this population. This trial was registered at clinicaltrials.gov as ISRCTN35739639. PMID- 27358414 TI - Dietary Iron Deficiency and Oversupplementation Increase Intestinal Permeability, Ion Transport, and Inflammation in Pigs. AB - BACKGROUND: Understanding the influence of dietary iron deficiency and dietary iron oversupplementation on intestinal health is important for both animal production and human health. OBJECTIVE: The aim of this study was to determine whether dietary iron concentration influences intestinal physiology, morphology, and inflammation in the porcine duodenum. METHODS: Twenty-four male pigs (21 d old) were fed diets containing either 20 mg Fe/kg [low dietary iron (L-Fe)], 120 mg Fe/kg [adequate dietary iron (A-Fe); control], or 520 mg Fe/kg [high dietary iron (H-Fe)] by FeSO4 supplement (dry matter basis). After 32-36 d, the duodenum was harvested from pigs and mounted in Ussing chambers for the measurement of transepithelial electrical resistance (TER), short-circuit current, and (3)H mannitol permeability. Intestinal morphology and inflammation were assessed by histologic examination, and proinflammatory gene expression was assessed by real time polymerase chain reaction. RESULTS: Compared with A-Fe-fed pigs, pigs fed L Fe diets exhibited reduced TER (by 30%; P < 0.05). Compared with that of A-Fe-fed controls, the paracellular flux of (3)H-mannitol across the duodenal mucosa was higher (P < 0.05) in L-Fe-fed (>100%) and H-Fe-fed (~4-fold) pigs; the L-Fe-fed and H-Fe-fed groups did not differ significantly from one another. Compared with the L-Fe-fed pigs, the A-Fe-fed and H-Fe-fed pigs had malondialdehyde concentrations 1.4- and 2.5-fold higher in the duodenum and 4.4- and 6.6-fold higher in the liver, respectively (P < 0.05). Neutrophil counts were higher in both the L-Fe-fed (by 3-fold) and H-Fe-fed (by 3.3-fold) groups than in the A-Fe fed group; the L-Fe-fed and H-Fe-fed groups did not significantly differ from one another. Duodenal mucosal tumor necrosis factor alpha (TNFA), interleukin (IL) 1beta, and IL6 relative gene expression was upregulated by 36%, 28%, and 45%, respectively, in H-Fe pigs (P < 0.05), but not in L-Fe pigs, compared with A-Fe pigs. CONCLUSION: These data suggest that adequate but not oversupplementation of dietary iron in pigs is required to maintain intestinal barrier health and function. PMID- 27358415 TI - Evaluation of Equations for Predicting 24-Hour Urinary Sodium Excretion from Casual Urine Samples in Asian Adults. AB - BACKGROUND: The collection of 24-h urine samples for the estimation of sodium intake is burdensome, and the utility of spot urine samples in Southeast Asian populations is unclear. OBJECTIVE: We aimed to assess the validity of prediction equations with the use of spot urine concentrations. METHODS: A sample of 144 Singapore residents of Chinese, Malay, and Indian ethnicity aged 18-79 y were recruited from the Singapore Health 2 Study conducted in 2014. Participants collected urine for 24 h in multiple small bottles on a single day. To determine the optimal collection time for a spot urine sample, a 1-mL sample was taken from a random bottle collected in the morning, afternoon, and evening. Published equations and a newly derived equation were used to predict 24-h sodium excretion from spot urine samples. RESULTS: The mean +/- SD concentration of sodium from the 24-h urine sample was 125 +/- 53.4 mmol/d, which is equivalent to 7.2 +/- 3.1 g salt. Bland-Altman plots showed good agreement at the group level between estimated and actual 24-h sodium excretion, with biases for the morning period of -3.5 mmol (95% CI: -14.8, 7.8 mmol; new equation) and 1.46 mmol (95% CI: -10.0, 13.0 mmol; Intersalt equation). A larger bias of 25.7 mmol (95% CI: 12.2, 39.3 mmol) was observed for the Tanaka equation in the morning period. The prediction accuracy did not differ significantly for spot urine samples collected at different times of the day or at a random time of day (P = 0.11-0.76). CONCLUSION: This study suggests that the application of both our own newly derived equation and the Intersalt equation to spot urine concentrations may be useful in predicting group means for 24-h sodium excretion in urban Asian populations. PMID- 27358416 TI - Development and Validation of an Empirical Dietary Inflammatory Index. AB - BACKGROUND: Knowledge on specific biological pathways mediating disease occurrence (e.g., inflammation) may be utilized to construct hypotheses-driven dietary patterns that take advantage of current evidence on disease-related hypotheses and the statistical methods of a posteriori patterns. OBJECTIVE: We developed and validated an empirical dietary inflammatory index (EDII) based on food groups. METHODS: We entered 39 pre-defined food groups in reduced rank regression models followed by stepwise linear regression analyses in the Nurses' Health Study (NHS, n = 5230) to identify a dietary pattern most predictive of 3 plasma inflammatory markers: interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor alpha receptor 2 (TNFalphaR2). We evaluated the construct validity of the EDII in 2 independent samples from NHS-II (n = 1002) and Health Professionals Follow-up Study (HPFS, n = 2632) using multivariable-adjusted linear regression models to examine how well the EDII predicted concentrations of IL-6, CRP, TNFalphaR2, adiponectin, and an overall inflammatory marker score combining all biomarkers. RESULTS: The EDII is the weighted sum of 18 food groups; 9 are anti-inflammatory and 9 proinflammatory. In NHS-II and HPFS, the EDII significantly predicted concentrations of all biomarkers. For example, the relative concentrations comparing extreme EDII quintiles in NHS-II were: adiponectin, 0.88 (95% CI, 0.80, 0.96), P-trend = 0.003; and CRP, 1.52 (95% CI, 1.18, 1.97), P-trend = 0.002. Corresponding associations in HPFS were: 0.87 (95% CI, 0.82, 0.92), P-trend < 0.0001; and 1.23 (95% CI, 1.09, 1.40), P-trend = 0.002. CONCLUSION: The EDII represents, to our knowledge, a novel, hypothesis driven, empirically derived dietary pattern that assesses diet quality based on its inflammatory potential. Its strong construct validity in independent samples of women and men indicates its usefulness in assessing the inflammatory potential of whole diets. Additionally, the EDII may be calculated in a standardized and reproducible manner across different populations thus circumventing a major limitation of dietary patterns derived from the same study in which they are applied. PMID- 27358417 TI - Consuming Iron Biofortified Beans Increases Iron Status in Rwandan Women after 128 Days in a Randomized Controlled Feeding Trial. AB - BACKGROUND: Food-based strategies to reduce nutritional iron deficiency have not been universally successful. Biofortification has the potential to become a sustainable, inexpensive, and effective solution. OBJECTIVE: This randomized controlled trial was conducted to determine the efficacy of iron-biofortified beans (Fe-Beans) to improve iron status in Rwandan women. METHODS: A total of 195 women (aged 18-27 y) with serum ferritin <20 MUg/L were randomly assigned to receive either Fe-Beans, with 86 mg Fe/kg, or standard unfortified beans (Control Beans), with 50 mg Fe/kg, 2 times/d for 128 d in Huye, Rwanda. Iron status was assessed by hemoglobin, serum ferritin, soluble transferrin receptor (sTfR), and body iron (BI); inflammation was assessed by serum C-reactive protein (CRP) and serum alpha1-acid glycoprotein (AGP). Anthropometric measurements were performed at baseline and at end line. Random weekly serial sampling was used to collect blood during the middle 8 wk of the feeding trial. Mixed-effects regression analysis with repeated measurements was used to evaluate the effect of Fe-Beans compared with Control-Beans on iron biomarkers throughout the course of the study. RESULTS: At baseline, 86% of subjects were iron-deficient (serum ferritin <15 MUg/L) and 37% were anemic (hemoglobin <120 g/L). Both groups consumed an average of 336 g wet beans/d. The Fe-Beans group consumed 14.5 +/- 1.6 mg Fe/d from biofortified beans, whereas the Control-Beans group consumed 8.6 +/- 0.8 mg Fe/d from standard beans (P < 0.05). Repeated-measures analyses showed significant time-by-treatment interactions for hemoglobin, log serum ferritin, and BI (P < 0.05). The Fe-Beans group had significantly greater increases in hemoglobin (3.8 g/L), log serum ferritin (0.1 log MUg/L), and BI (0.5 mg/kg) than did controls after 128 d. For every 1 g Fe consumed from beans over the 128 study days, there was a significant 4.2-g/L increase in hemoglobin (P < 0.05). CONCLUSION: The consumption of iron-biofortified beans significantly improved iron status in Rwandan women. This trial was registered at clinicaltrials.gov as NCT01594359. PMID- 27358418 TI - Delaying Iron Therapy until 28 Days after Antimalarial Treatment Is Associated with Greater Iron Incorporation and Equivalent Hematologic Recovery after 56 Days in Children: A Randomized Controlled Trial. AB - BACKGROUND: Iron therapy begun concurrently with antimalarial treatment may not be well absorbed because of malaria-induced inflammation. Delaying the start of iron therapy may permit better iron absorption and distribution. OBJECTIVE: We compared erythrocyte iron incorporation in children who started iron supplementation concurrently with antimalarial treatment or 28 d later. We hypothesized that delayed iron supplementation would be associated with greater incorporation and better hematologic recovery. METHODS: We enrolled 100 children aged 6-59 mo with malaria and hemoglobin concentrations of 50.0-99.9 g/L who presented to Mulago Hospital, Kampala, into a randomized trial of iron therapy. All children were administered antimalarial treatment. Children with zinc protoporphyrin (ZPP) >=80 MUmol/mol heme were randomly assigned to start iron supplementation concurrently with the antimalarial treatment [immediate iron (I) group] or 28 d later [delayed iron (D) group]. All children were administered iron-stable isotope (57)Fe on day 0 and (58)Fe on day 28. We compared the percentage of iron incorporation at the start of supplementation (I group at day 0 compared with D group at day 28, aim 1) and hematologic recovery at day 56 (aim 2). RESULTS: The percentage of iron incorporation (mean +/- SE) was greater at day 28 in the D group (16.5% +/- 1.7%) than at day 0 in the I group (7.9% +/- 0.5%; P < 0.001). On day 56, concentrations of hemoglobin and ZPP and plasma ferritin, soluble transferrin receptor (sTfR), hepcidin, and C-reactive protein did not differ between the groups. On day 28, the hemoglobin (mean +/- SD) and plasma iron markers (geometric mean; 95% CI) reflected poorer iron status in the D group than in the I group at this intervening time as follows: hemoglobin (105 +/- 15.9 compared with 112 +/- 12.4 g/L; P = 0.04), ferritin (39.3 MUg/L; 23.5, 65.7 MUg/L compared with 79.9 MUg/L; 58.3, 110 MUg/L; P = 0.02), sTfR (8.9 mg/L; 7.4, 10.7 mg/L compared with 6.7 mg/L; 6.1, 7.5 mg/L; P = 0.01), and hepcidin (13.3 ng/mL; 8.3, 21.2 ng/mL compared with 38.8 ng/mL; 28.3, 53.3 ng/mL; P < 0.001). CONCLUSIONS: Delaying the start of iron improves incorporation but leads to equivalent hematologic recovery at day 56 in Ugandan children with malaria and anemia. These results do not demonstrate a clear, short-term benefit of delaying iron. This trial was registered at clinicaltrials.gov as NCT01754701. PMID- 27358419 TI - Participating in a Food-Assisted Maternal and Child Nutrition and Health Program in Rural Guatemala Alters Household Dietary Choices. AB - BACKGROUND: Food assistance programs may alter food choices, but factors determining households' decisions regarding food acquisition, preparation, and consumption in the context of food aid are not well understood. OBJECTIVE: This study aimed to understand how the Programa Comunitario Materno Infantil de Diversificacion Alimentaria (Mother-Child Community Food Diversification Program; PROCOMIDA), a food-assisted maternal and child health and nutrition program in rural Alta Verapaz, Guatemala, altered household food choices. METHODS: We conducted semistructured interviews and focus groups with 63 households in 3 participating (n = 32 households) and 3 control (n = 31) villages. A last-day food recall (without estimating quantities) and food-frequency questionnaire that used food cards assessed dietary choices. Qualitative analysis used thematic a priori and emergent coding; food group consumption frequencies were analyzed by using 2-level, logistic, mixed modeling, and chi-square testing while accounting for community clustering. RESULTS: Compared with control households, PROCOMIDA changed household food choices through a combination of providing food resources (with monthly food rations) and new knowledge and skills related to health and food (in the program's behavior change communication component) while reinforcing existing knowledge and beliefs. PROCOMIDA families consumed rice, red beans, and oil more frequently than did control families (differences of 2.20 (P < 0.001), 2.68 (P < 0.001), and 1.64 (P = 0.038) times/wk, respectively); these foods were in the rations. PROCOMIDA families also ate chicken, local plants, and some vegetables more frequently. The importance of these foods was emphasized in the behavioral change communication component; these foods may have been more accessible because provision of food rations freed resources. CONCLUSION: Our findings suggest that if a program provides food free of cost to rural indigenous families in the context of a maternal and child nutrition and health program, it may be important to include a well-designed behavioral change communication component to improve household food choices. PMID- 27358420 TI - Greater Amino Acid Intake Is Required to Maximize Whole-Body Protein Synthesis Immediately after Endurance Exercise Than at Rest in Endurance-Trained Rats, as Determined by an Indicator Amino Acid Oxidation Method. AB - BACKGROUND: The indicator amino acid oxidation (IAAO) method has contributed to establishing protein and amino acid (AA) requirements by determining the optimal protein and AA intake that maximizes whole-body protein synthesis. However, it has not been used with endurance-trained subjects. OBJECTIVE: This study aimed to determine the optimal AA intake immediately after endurance exercise and at rest in endurance-trained rats by using the IAAO method. METHODS: Four-week-old male Fischer rats were divided into a sedentary (SED) group and a trained (TR) group, which underwent treadmill training 5 d/wk for 6 wk at 26 m/min for 60 min/d. On the metabolic trial day, half of the TR group was provided with test diets after daily treadmill running (TR-PostEx). The other half of the TR group (TR-Rest) and all of the SED group were provided with test diets while at rest. The test diets contained different amounts of AAs (3.3-37.3 g ? kg(-1) ? d(-1)). Phenylalanine in the test diet was replaced with L-[1-(13)C]phenylalanine. The phenylalanine oxidation rate (PheOx) was determined with (13)CO2 enrichment in breath, CO2 excretion rate, and enrichment of phenylalanine in blood during the feeding period. The optimal AA intake was determined with biphasic mixed linear regression crossover analysis for PheOx, which identified a breakpoint at the minimal PheOx in response to graded amounts of AA intake. RESULTS: The optimal AA intake in the TR-PostEx group (26.8 g ? kg(-1) ? d(-1); 95% CI: 21.5, 32.1 g ? kg(-1) ? d(-1)) was significantly higher than in the SED (15.1 g ? kg(-1) ? d( 1); 95% CI: 11.1, 19.1 g ? kg(-1) ? d(-1)) and TR-Rest (13.3 g ? kg(-1) ? d(-1); 95% CI: 10.9, 15.7 g ? kg(-1) ? d(-1)) groups, which did not differ. CONCLUSIONS: Greater AA intake is required to maximize whole-body protein synthesis immediately after endurance exercise than at rest, but not at rest in endurance trained rats. PMID- 27358421 TI - Vitamin D Receptor Gene Polymorphisms Are Associated with Abdominal Visceral Adipose Tissue Volume and Serum Adipokine Concentrations but Not with Body Mass Index or Waist Circumference in African Americans: The Jackson Heart Study. AB - BACKGROUND: The biological actions of vitamin D are mediated through the vitamin D receptor (VDR). Single-nucleotide polymorphisms (SNPs) in the VDR gene have been previously associated with adiposity traits. However, to our knowledge, few studies have included direct measures of adiposity and adipokine concentrations. OBJECTIVE: We examined the association of tagging SNPs in the VDR gene with multiple adiposity measures, including waist circumference (WC), body mass index (BMI), body fat percentage, subcutaneous and visceral adipose tissue (VAT) volume, and serum adipokine (adiponectin and leptin) concentrations in adult African Americans (AAs). METHODS: Data from 3020 participants (61.9% women; mean age, 54.6 y) from the Jackson Heart Study were used for this analysis. Forty-five tag SNPs were chosen with the use of genotype data from the International HapMap project. We used linear regression to test the associations of imputed VDR SNPs with each of the traits, adjusted for age, sex, educational status, physical activity, smoking, alcohol intake, serum vitamin D concentration, European ancestry, and multiple testing. RESULTS: The G allele of the SNP rs4328262 remained associated with increased VAT volume after multiple testing correction (beta = 45.7; P < 0.001). The A allele of another SNP (rs11574070) was nominally associated with body fat percentage (beta = 0.96; P = 0.002). None of the VDR SNPs analyzed showed any link with WC or BMI. The A allele of rs2228570 (beta = 0.08; P = 0.001) for men and the T allele of rs2853563 (beta = 0.04; P < 0.001) for women remained positively associated with serum adiponectin concentrations after multiple testing correction. CONCLUSION: Although we did not find any association for anthropometric measures, we did observe associations of VDR variants with serum adipokines and with the more metabolically active fat, VAT. Therefore, our findings demonstrate a possible role of VDR variants in regulating adipose tissue activity and adiposity among AAs. PMID- 27358422 TI - Greater Healthful Dietary Variety Is Associated with Greater 2-Year Changes in Weight and Adiposity in the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) Trial. AB - BACKGROUND: Greater healthful dietary variety has been inversely associated with body adiposity cross-sectionally; however, it remains unknown whether it can improve long-term weight loss. OBJECTIVE: This study prospectively examined associations between healthful dietary variety and short-term (6 mo) and long term (2 y) changes in adiposity in the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) weight-loss trial completed in 2007. METHODS: Healthful dietary variety was assessed from 24-h recalls with the use of the US Healthy Food Diversity index among participants aged 30-70 y with overweight/obesity (n = 367). Changes in the index between baseline and 6 mo were divided into tertiles representing reduced (T1), stable (T2), or increased variety (T3). Body weight and waist circumference (WC) were measured every 6 mo, and the percentage of body fat and trunk fat were measured at 6 mo and 2 y. Associations between changes in variety and short-term and long-term changes in adiposity were analyzed by use of multivariable-adjusted generalized linear models and repeated-measures ANOVA. RESULTS: Regardless of dietary arm, T3 compared with T2 was associated with greater reduction in weight (-8.6 compared with -6.7 kg), WC (-9.1 compared with 6.1 cm), and body fat at 6 mo (beta = -4.61 kg, P < 0.05). At 2 y, individuals in T3 compared with those in T2 or T1 maintained greater weight loss [-4.0 (T3) compared with -1.8 kg (T2 and T1), P = 0.02] and WC reduction [-5.4 (T3) compared with -3.0 (T2) and -2.9 cm (T1), P = 0.01]. Total body fat and trunk fat reductions were similarly greater in T3 than in T2. CONCLUSIONS: Increasing healthful food variety in energy-restricted diets may improve sustained reductions in weight and adiposity among adults with overweight or obesity on weight-loss regimens. This trial is registered at clinicaltrials.gov as NCT00072995. PMID- 27358423 TI - The Variable Regions of Lactobacillus rhamnosus Genomes Reveal the Dynamic Evolution of Metabolic and Host-Adaptation Repertoires. AB - Lactobacillus rhamnosus is a diverse Gram-positive species with strains isolated from different ecological niches. Here, we report the genome sequence analysis of 40 diverse strains of L. rhamnosus and their genomic comparison, with a focus on the variable genome. Genomic comparison of 40 L. rhamnosus strains discriminated the conserved genes (core genome) and regions of plasticity involving frequent rearrangements and horizontal transfer (variome). The L. rhamnosus core genome encompasses 2,164 genes, out of 4,711 genes in total (the pan-genome). The accessory genome is dominated by genes encoding carbohydrate transport and metabolism, extracellular polysaccharides (EPS) biosynthesis, bacteriocin production, pili production, the cas system, and the associated clustered regularly interspaced short palindromic repeat (CRISPR) loci, and more than 100 transporter functions and mobile genetic elements like phages, plasmid genes, and transposons. A clade distribution based on amino acid differences between core (shared) proteins matched with the clade distribution obtained from the presence absence of variable genes. The phylogenetic and variome tree overlap indicated that frequent events of gene acquisition and loss dominated the evolutionary segregation of the strains within this species, which is paralleled by evolutionary diversification of core gene functions. The CRISPR-Cas system could have contributed to this evolutionary segregation. Lactobacillus rhamnosus strains contain the genetic and metabolic machinery with strain-specific gene functions required to adapt to a large range of environments. A remarkable congruency of the evolutionary relatedness of the strains' core and variome functions, possibly favoring interspecies genetic exchanges, underlines the importance of gene-acquisition and loss within the L. rhamnosus strain diversification. PMID- 27358424 TI - Molecular Evolutionary Consequences of Island Colonization. AB - Island endemics are expected to have low effective population sizes (Ne), first because some may experience population bottlenecks when they are founded, and second because they have restricted ranges. Therefore, we expect island species to have reduced genetic diversity, inefficient selection, and reduced adaptive potential compared with their mainland counterparts. We used both polymorphism and substitution data to address these predictions, improving on the approach of recent studies that only used substitution data. This allowed us to directly test the assumption that island species have small values of Ne We found that island species had significantly less genetic diversity than mainland species; however, this pattern could be attributed to a subset of island species that appeared to have undergone a recent population bottleneck. When these species were excluded from the analysis, island and mainland species had similar levels of genetic diversity, despite island species occupying considerably smaller areas than their mainland counterparts. We also found no overall difference between island and mainland species in terms of the effectiveness of selection or the mutation rate. Our evidence suggests that island colonization has no lasting impact on molecular evolution. This surprising result highlights gaps in our knowledge of the relationship between census and effective population size. PMID- 27358425 TI - Assembled Plastid and Mitochondrial Genomes, as well as Nuclear Genes, Place the Parasite Family Cynomoriaceae in the Saxifragales. AB - Cynomoriaceae, one of the last unplaced families of flowering plants, comprise one or two species or subspecies of root parasites that occur from the Mediterranean to the Gobi Desert. Using Illumina sequencing, we assembled the mitochondrial and plastid genomes as well as some nuclear genes of a Cynomorium specimen from Italy. Selected genes were also obtained by Sanger sequencing from individuals collected in China and Iran, resulting in matrices of 33 mitochondrial, 6 nuclear, and 14 plastid genes and rDNAs enlarged to include a representative angiosperm taxon sampling based on data available in GenBank. We also compiled a new geographic map to discern possible discontinuities in the parasites' occurrence. Cynomorium has large genomes of 13.70-13.61 (Italy) to 13.95-13.76 pg (China). Its mitochondrial genome consists of up to 49 circular subgenomes and has an overall gene content similar to that of photosynthetic angiosperms, while its plastome retains only 27 of the normally 116 genes. Nuclear, plastid and mitochondrial phylogenies place Cynomoriaceae in Saxifragales, and we found evidence for several horizontal gene transfers from different hosts, as well as intracellular gene transfers. PMID- 27358426 TI - Y-Chromosome Structural Diversity in the Bonobo and Chimpanzee Lineages. AB - The male-specific regions of primate Y-chromosomes (MSY) are enriched for multi copy genes highly expressed in the testis. These genes are located in large repetitive sequences arranged as palindromes, inverted-, and tandem repeats termed amplicons. In humans, these genes have critical roles in male fertility and are essential for the production of sperm. The structure of human and chimpanzee amplicon sequences show remarkable difference relative to the remainder of the genome, a difference that may be the result of intense selective pressure on male fertility. Four subspecies of common chimpanzees have undergone extended periods of isolation and appear to be in the early process of subspeciation. A recent study found amplicons enriched for testis-expressed genes on the primate X-chromosome the target of hard selective sweeps, and male fertility genes on the Y-chromosome may also be the targets of selection. However, little is understood about Y-chromosome amplicon diversity within and across chimpanzee populations. Here, we analyze nine common chimpanzee (representing three subspecies: Pan troglodytes schweinfurthii, Pan troglodytes ellioti, and Pan troglodytes verus) and two bonobo (Pan paniscus) male whole genome sequences to assess Y ampliconic copy-number diversity across the Pan genus. We observe that the copy number of Y chromosome amplicons is variable among chimpanzees and bonobos, and identify several lineage-specific patterns, including variable copy number of azoospermia candidates RBMY and DAZ We detect recurrent switchpoints of copy-number change along the ampliconic tracts across chimpanzee populations, which may be the result of localized genome instability or selective forces. PMID- 27358427 TI - Evolution of the Calcium-Based Intracellular Signaling System. AB - To progress our understanding of molecular evolution from a collection of well studied genes toward the level of the cell, we must consider whole systems. Here, we reveal the evolution of an important intracellular signaling system. The calcium-signaling toolkit is made up of different multidomain proteins that have undergone duplication, recombination, sequence divergence, and selection. The picture of evolution, considering the repertoire of proteins in the toolkit of both extant organisms and ancestors, is radically different from that of other systems. In eukaryotes, the repertoire increased in both abundance and diversity at a far greater rate than general genomic expansion. We describe how calcium based intracellular signaling evolution differs not only in rate but in nature, and how this correlates with the disparity of plants and animals. PMID- 27358428 TI - Complete Genome of the Starch-Degrading Myxobacteria Sandaracinus amylolyticus DSM 53668T. AB - Myxobacteria are members of delta-proteobacteria and are typified by large genomes, well-coordinated social behavior, gliding motility, and starvation induced fruiting body formation. Here, we report the 10.33 Mb whole genome of a starch-degrading myxobacterium Sandaracinus amylolyticus DSM 53668(T) that encodes 8,962 proteins, 56 tRNA, and two rRNA operons. Phylogenetic analysis, in silico DNA-DNA hybridization and average nucleotide identity reveal its divergence from other myxobacterial species and support its taxonomic characterization into a separate family Sandaracinaceae, within the suborder Sorangiineae. Sequence similarity searches using the Carbohydrate-active enzymes (CAZyme) database help identify the enzyme repertoire of S. amylolyticus involved in starch, agar, chitin, and cellulose degradation. We identified 16 alpha amylases and two gamma-amylases in the S. amylolyticus genome that likely play a role in starch degradation. While many of the amylases are seen conserved in other delta-proteobacteria, we notice several novel amylases acquired via horizontal transfer from members belonging to phylum Deinococcus-Thermus, Acidobacteria, and Cyanobacteria. No agar degrading enzyme(s) were identified in the S. amylolyticus genome. Interestingly, several putative beta-glucosidases and endoglucanases proteins involved in cellulose degradation were identified. However, the absence of cellobiohydrolases/exoglucanases corroborates with the lack of cellulose degradation by this bacteria. PMID- 27358432 TI - Long-Term Risk of Atherosclerotic Cardiovascular Disease in US Adults With the Familial Hypercholesterolemia Phenotype. AB - BACKGROUND: Heterozygous familial hypercholesterolemia (FH) affects up to 1 in 200 individuals in the United States, but atherosclerotic cardiovascular disease (ASCVD) outcomes of FH in the general US population have not been described. We therefore sought to evaluate long-term coronary heart disease (CHD) and total ASCVD risks in US adults with an FH phenotype. METHODS: Using individual pooled data from 6 large US epidemiological cohorts, we stratified participants by low density lipoprotein cholesterol level at index ages from 20 to 79 years. For the primary analysis, low-density lipoprotein cholesterol levels >=190 and <130 mg/dL defined the FH phenotype and referent, respectively. Sensitivity analyses evaluated the effects of varying the FH phenotype definition. We used Cox regression models to assess covariate-adjusted associations of the FH phenotype with 30-year hazards for CHD (CHD death or nonfatal myocardial infarction) and total ASCVD (CHD or stroke). RESULTS: We included 68 565 baseline person examinations; 3850 (5.6%) had the FH phenotype by the primary definition. Follow up across index ages ranged from 78 985 to 308 378 person-years. After covariate adjustment, the FH phenotype was associated with substantially elevated 30-year CHD risk, with hazard ratios up to 5.0 (95% confidence interval, 1.1-21.7). Across index ages, CHD risk was accelerated in those with the FH phenotype by 10 to 20 years in men and 20 to 30 years in women. Similar patterns of results were found for total ASCVD risk, with hazard ratios up to 4.1 (95% confidence interval, 1.2-13.4). Alternative FH phenotype definitions incorporating family history, more stringent age-based low-density lipoprotein cholesterol thresholds, or alternative lipid fractions decreased the FH phenotype prevalence to as low as 0.2% to 0.4% without materially affecting CHD risk estimates (hazard ratios up to 8.0; 95% confidence interval, 1.0-61.6). CONCLUSIONS: In the general US population, the long-term ASCVD burden related to phenotypic FH, defined by low density lipoprotein cholesterol >=190 mg/dL, is likely substantial. Our finding of CHD risk acceleration may aid efforts in risk communication. PMID- 27358433 TI - Enough Evidence, Time to Act! PMID- 27358434 TI - Impact of Renal Function on Outcomes With Edoxaban in the ENGAGE AF-TIMI 48 Trial. AB - BACKGROUND: Edoxaban, an oral factor Xa inhibitor with 50% renal clearance, was noninferior to well-managed warfarin for stroke or systemic embolism (S/SE) prevention and reduced bleeding in patients with atrial fibrillation. We evaluated the efficacy and safety of edoxaban versus warfarin across the range of baseline creatinine clearance (CrCl) in the ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation Thrombolysis in Myocardial Infarction Study 48) with a focus on the higher-dose edoxaban regimen (HDER) and the upper range of CrCl. METHODS: A total of 14 071 patients with atrial fibrillation at moderate to high risk for stroke were randomized to warfarin or HDER (60 mg daily or a 50% dose reduction to 30 mg daily for CrCl 30-50 mL/min, body weight of <=60 kg, or use of a potent phosphorylated glycoprotein inhibitor). CrCl <30 mL/min was exclusionary. End points of S/SE, International Society on Thrombosis and Haemostasis major bleeding, and the net clinical outcome of S/SE/major bleeding or death were evaluated by intention-to-treat analysis using the prespecified CrCl cut point of 50 mL/min and additional exploratory cut points with the Cockcroft-Gault formula. A sensitivity analysis was performed with the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula for estimating renal function. RESULTS: The relative risk of S/SE with HDER versus warfarin in patients with CrCl >50 mL/min (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.72-1.04) was similar to that in patients with CrCl <=50 mL/min (HR, 0.87; 95% CI, 0.65-1.18; P for interaction=0.94). Several exploratory analyses suggested lower relative efficacy for the prevention of S/SE with HDER compared with warfarin at higher levels of CrCl (CrCl <=50 mL/min: HR, 0.87; 95% CI, 0.65-1.18; CrCl >50-95 mL/min: HR, 0.78; 95% CI, 0.64-0.96; CrCl >95 mL/min: HR, 1.36; 95% CI, 0.88-2.10; P for interaction=0.08). Bleeding rates were lower at all levels of CrCl with HDER (P for interaction=0.11). Because of the preserved effect on bleeding, the net clinical outcome was more favorable with HDER across the range of CrCl (P for interaction=0.73). Similar findings were observed in the sensitivity analysis using the CKD-EPI formula. CONCLUSIONS: Although there was an apparent decrease in relative efficacy to prevent arterial thromboembolism in the upper range of CrCl, the safety and net clinical benefit of HDER compared with warfarin are consistent across the range of renal function. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00781391. PMID- 27358436 TI - Renal Function in Atrial Fibrillation: A Multifaceted Dilemma. PMID- 27358435 TI - On-Treatment Outcomes in Patients With Worsening Renal Function With Rivaroxaban Compared With Warfarin: Insights From ROCKET AF. AB - BACKGROUND: Despite rapid clinical adoption of novel anticoagulants, it is unknown whether outcomes differ among patients with worsening renal function (WRF) taking these new drugs compared with warfarin. We aimed to determine whether the primary efficacy (stroke or systemic embolism) and safety (major bleeding and nonmajor clinically relevant bleeding) end points from the ROCKET AF trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial) differed among participants with WRF taking rivaroxaban and those taking warfarin. METHODS: After excluding patients without at least 1 follow-up creatinine measurement (n=1624), we included all remaining patients (n=12 612) randomly assigned to either rivaroxaban or dose-adjusted warfarin. On treatment WRF (a decrease of >20% from screening creatinine clearance measurement at any time point during the study) was evaluated as a time-dependent covariate in Cox proportional hazards models. RESULTS: Baseline characteristics were generally similar between patients with stable renal function (n=9292) and WRF (n=3320). Rates of stroke or systemic embolism, myocardial infarction, and bleeding were also similar, but WRF patients experienced a higher incidence of vascular death versus stable renal function (2.21 versus 1.41 events per 100 patient-years; P=0.026). WRF patients who were randomized to receive rivaroxaban had a reduction in stroke or systemic embolism compared with those taking warfarin (1.54 versus 3.25 events per 100 patient-years) that was not seen in patients with stable renal function who were randomized to receive rivaroxaban (P=0.050 for interaction). There was no difference in major or nonmajor clinically relevant bleeding among WRF patients randomized to warfarin versus rivaroxaban. CONCLUSIONS: Among patients with on-treatment WRF, rivaroxaban was associated with lower rates of stroke and systemic embolism compared with warfarin, without an increase in the composite bleeding end point. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767. PMID- 27358437 TI - Randomized, Controlled Trial of an Advance Care Planning Video Decision Support Tool for Patients With Advanced Heart Failure. AB - BACKGROUND: Conversations about goals of care and cardiopulmonary resuscitation (CPR)/intubation for patients with advanced heart failure can be difficult. This study examined the impact of a video decision support tool and patient checklist on advance care planning for patients with heart failure. METHODS: This was a multisite, randomized, controlled trial of a video-assisted intervention and advance care planning checklist versus a verbal description in 246 patients >=64 years of age with heart failure and an estimated likelihood of death of >50% within 2 years. Intervention participants received a verbal description for goals of care (life-prolonging care, limited care, and comfort care) and CPR/intubation plus a 6-minute video depicting the 3 levels of care, CPR/intubation, and an advance care planning checklist. Control subjects received only the verbal description. The primary analysis compared the proportion of patients preferring comfort care between study arms immediately after the intervention. Secondary outcomes were CPR/intubation preferences and knowledge (6-item test; range, 0-6) after intervention. RESULTS: In the intervention group, 27 (22%) chose life prolonging care, 31 (25%) chose limited care, 63 (51%) selected comfort care, and 2 (2%) were uncertain. In the control group, 50 (41%) chose life-prolonging care, 27 (22%) selected limited care, 37 (30%) chose comfort care, and 8 (7%) were uncertain (P<0.001). Intervention participants (compared with control subjects) were more likely to forgo CPR (68% versus 35%; P<0.001) and intubation (77% versus 48%; P<0.001) and had higher mean knowledge scores (4.1 versus 3.0; P<0.001). CONCLUSIONS: Patients with heart failure who viewed a video were more informed, more likely to select a focus on comfort, and less likely to desire CPR/intubation compared with patients receiving verbal information only. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01589120. PMID- 27358438 TI - The Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Nephrotic Syndrome Associated Hypercholesterolemia. AB - BACKGROUND: In nephrotic syndrome, damage to the podocytes of the kidney produces severe hypercholesterolemia for which novel treatments are urgently needed. PCSK9 (proprotein convertase subtilisin/kexin type 9) has emerged as an important regulator of plasma cholesterol levels and therapeutic target. Here, we tested the role of PCSK9 in mediating the hypercholesterolemia of nephrotic syndrome. METHODS: PCSK9 and plasma lipids were studied in nephrotic syndrome patients before and after remission of disease, mice with genetic ablation of the podocyte (Podocyte Apoptosis Through Targeted Activation of Caspase-8, Pod-ATTAC mice) and mice treated with nephrotoxic serum (NTS), which triggers immune-mediated podocyte damage. In addition, mice with hepatic deletion of Pcsk9 were treated with NTS to determine the contribution of PCSK9 to the dyslipidemia of nephrotic syndrome. RESULTS: Patients with nephrotic syndrome showed a decrease in plasma cholesterol and plasma PCSK9 on remission of their disease (P<0.05, n=47-50). Conversely, Pod-ATTAC mice and NTS-treated mice showed hypercholesterolemia and a 7- to 24-fold induction in plasma PCSK9. The induction of plasma PCSK9 appeared to be attributable to increased secretion of PCSK9 from the hepatocyte coupled with decreased clearance. Interestingly, knockout of Pcsk9ameliorated the effects of NTS on plasma lipids. Thus, in the presence of NTS, mice lacking hepatic Pcsk9 showed a 40% to 50% decrease in plasma cholesterol and triglycerides. Moreover, the ability of NTS treatment to increase the percentage of low-density lipoprotein-associated cholesterol (from 9% in vehicle-treated Flox mice to 47% after NTS treatment), was lost in mice with hepatic deletion of Pcsk9 (5% in both the presence and absence of NTS). CONCLUSIONS: Podocyte damage triggers marked inductions in plasma PCSK9, and knockout of Pcsk9 ameliorates dyslipidemia in a mouse model of nephrotic syndrome. These data suggest that PCSK9 inhibitors may be beneficial in patients with nephrotic syndrome-associated hypercholesterolemia. PMID- 27358440 TI - Letter by Dizman et al Regarding Article, "Periodontitis Increases the Risk of a First Myocardial Infarction: A Report From the PAROKRANK Study". PMID- 27358441 TI - Response by Ryden to Letter Regarding Article, "Periodontitis Increases the Risk of a First Myocardial Infarction: A Report From the PAROKRANK Study". PMID- 27358442 TI - Influence of menu labeling on food choices in real-life settings: a systematic review. AB - CONTEXT: Evidence that menu labeling influences food choices in real-life settings is lacking. Reviews usually focus on calorie counts without addressing broader issues related to healthy eating. OBJECTIVE: This systematic review assessed the influence of diverse menu-labeling formats on food choices in real life settings. DATA SOURCES: Several databases were searched: Cochrane Library, Scopus, MEDLINE, Web of Science, Food Science and Technology Abstracts, Biological Abstracts, CAB Abstracts, EconLit, SciELO, and LILACS. STUDY SELECTION: Articles reporting experiments, quasi-experiments, and observational studies using control or preintervention groups were selected blindly by two reviewers. DATA EXTRACTION: Data was extracted using a standard form. Analyses differentiated between foodservice types. The quality of the 38 included studies was assessed blindly by two reviewers. DATA ANALYSIS: The results were mixed, but a partial influence of menu labeling on food choices was more frequent than an overall influence or no influence. Menu labeling was more effective in cafeterias than in restaurants. Qualitative information, such as healthy-food symbols and traffic-light labeling, was most effective in promoting healthy eating. In general, the studies were of moderate quality and did not use control groups. CONCLUSIONS: Calorie labeling in menus is not effective to promote healthier food choices. Further research in real-life settings with control groups should test diverse qualitative information in menu labeling. PMID- 27358439 TI - Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction: A Multiorgan Roadmap. AB - Heart failure (HF) with preserved ejection fraction (EF; HFpEF) accounts for 50% of HF cases, and its prevalence relative to HF with reduced EF continues to rise. In contrast to HF with reduced EF, large trials testing neurohumoral inhibition in HFpEF failed to reach a positive outcome. This failure was recently attributed to distinct systemic and myocardial signaling in HFpEF and to diversity of HFpEF phenotypes. In this review, an HFpEF treatment strategy is proposed that addresses HFpEF-specific signaling and phenotypic diversity. In HFpEF, extracardiac comorbidities such as metabolic risk, arterial hypertension, and renal insufficiency drive left ventricular remodeling and dysfunction through systemic inflammation and coronary microvascular endothelial dysfunction. The latter affects left ventricular diastolic dysfunction through macrophage infiltration, resulting in interstitial fibrosis, and through altered paracrine signaling to cardiomyocytes, which become hypertrophied and stiff because of low nitric oxide and cyclic guanosine monophosphate. Systemic inflammation also affects other organs such as lungs, skeletal muscle, and kidneys, leading, respectively, to pulmonary hypertension, muscle weakness, and sodium retention. Individual steps of these signaling cascades can be targeted by specific interventions: metabolic risk by caloric restriction, systemic inflammation by statins, pulmonary hypertension by phosphodiesterase 5 inhibitors, muscle weakness by exercise training, sodium retention by diuretics and monitoring devices, myocardial nitric oxide bioavailability by inorganic nitrate-nitrite, myocardial cyclic guanosine monophosphate content by neprilysin or phosphodiesterase 9 inhibition, and myocardial fibrosis by spironolactone. Because of phenotypic diversity in HFpEF, personalized therapeutic strategies are proposed, which are configured in a matrix with HFpEF presentations in the abscissa and HFpEF predispositions in the ordinate. PMID- 27358443 TI - Bridging the Gap between DNA Methylation, DNA Methylation Readers, and Neurodevelopmental Disorders. PMID- 27358444 TI - Propagating Cortical Waves May Underlie Illusory Motion Perception. PMID- 27358445 TI - Muscle IL1beta Drives Ischemic Myalgia via ASIC3-Mediated Sensory Neuron Sensitization. AB - Musculoskeletal pain is a significantly common clinical complaint. Although it is known that muscles are quite sensitive to alterations in blood flow/oxygenation and a number of muscle pain disorders are based in problems of peripheral perfusion, the mechanisms by which ischemic-like conditions generate myalgia remain unclear. We found, using a multidisciplinary experimental approach, that ischemia and reperfusion injury (I/R) in male Swiss Webster mice altered ongoing and evoked pain-related behaviors in addition to activity levels through enhanced muscle interleukin-1 beta (IL1beta)/IL1 receptor signaling to group III/IV muscle afferents. Peripheral sensitization depended on acid-sensing ion channels (ASICs) because treatment of sensory afferents in vitro with IL1beta-upregulated ASIC3 in single cells, and nerve-specific knock-down of ASIC3 recapitulated the results of inhibiting the enhanced IL1beta/IL1r1 signaling after I/R, which was also found to regulate afferent sensitization and pain-related behaviors. This suggests that targeting muscle IL1beta signaling may be a potential analgesic therapy for ischemic myalgia. SIGNIFICANCE STATEMENT: Here, we have described a novel pathway whereby increased inflammation within the muscle tissue during ischemia/reperfusion injury sensitizes group III and IV muscle afferents via upregulation of acid-sensing ion channel 3 (ASIC3), leading not only to alterations in mechanical and chemical responsiveness in individual afferents, but also to pain-related behavioral changes. Furthermore, these I/R-induced changes can be prevented using an afferent-specific siRNA knock-down strategy targeting either ASIC3 or the upstream mediator of its expression, interleukin 1 receptor 1. Therefore, this knowledge may contribute to the development of alternative therapeutics for muscle pain and may be especially relevant to pain caused by issues of peripheral circulation, which is commonly observed in disorders such as complex regional pain syndrome, sickle cell anemia, or fibromyalgia. PMID- 27358446 TI - fMRI Syntactic and Lexical Repetition Effects Reveal the Initial Stages of Learning a New Language. AB - When learning a new language, we build brain networks to process and represent the acquired words and syntax and integrate these with existing language representations. It is an open question whether the same or different neural mechanisms are involved in learning and processing a novel language compared with the native language(s). Here we investigated the neural repetition effects of repeating known and novel word orders while human subjects were in the early stages of learning a new language. Combining a miniature language with a syntactic priming paradigm, we examined the neural correlates of language learning on-line using functional magnetic resonance imaging. In left inferior frontal gyrus and posterior temporal cortex, the repetition of novel syntactic structures led to repetition enhancement, whereas repetition of known structures resulted in repetition suppression. Additional verb repetition led to an increase in the syntactic repetition enhancement effect in language-related brain regions. Similarly, the repetition of verbs led to repetition enhancement effects in areas related to lexical and semantic processing, an effect that continued to increase in a subset of these regions. Repetition enhancement might reflect a mechanism to build and strengthen a neural network to process novel syntactic structures and lexical items. By contrast, the observed repetition suppression points to overlapping neural mechanisms for native and new language constructions when these have sufficient structural similarities. SIGNIFICANCE STATEMENT: Acquiring a second language entails learning how to interpret novel words and relations between words, and to integrate them with existing language knowledge. To investigate the brain mechanisms involved in this particularly human skill, we combined an artificial language learning task with a syntactic repetition paradigm. We show that the repetition of novel syntactic structures, as well as words in contexts, leads to repetition enhancement, whereas repetition of known structures results in repetition suppression. We thus propose that repetition enhancement might reflect a brain mechanism to build and strengthen a neural network to process novel syntactic regularities and novel words. Importantly, the results also indicate an overlap in neural mechanisms for native and new language constructions with sufficient structural similarities. PMID- 27358447 TI - Extension of Helix 12 in Munc18-1 Induces Vesicle Priming. AB - Munc18-1 is essential for vesicle fusion and participates in the docking of large dense-core vesicles to the plasma membrane. Recent structural data suggest that conformational changes in the 12th helix of the Munc18-1 domain 3a within the Munc18-1:syntaxin complex result in an additional interaction with synaptobrevin 2/VAMP2 (vesicle-associated membrane protein 2), leading to SNARE complex formation. To test this hypothesis in living cells, we examined secretion from Munc18-1-null mouse adrenal chromaffin cells expressing Munc18-1 mutants designed to either perturb the extension of helix 12 (Delta324-339), block its interaction with synaptobrevin-2 (L348R), or extend the helix to promote coil-coil interactions with other proteins (P335A). The mutants rescued vesicle docking and syntaxin-1 targeting to the plasma membrane, with the exception of P335A that only supported partial syntaxin-1 targeting. Disruptive mutations (L348R or Delta324-339) lowered the secretory amplitude by decreasing vesicle priming, whereas P335A markedly increased priming and secretory amplitude. The mutants displayed unchanged kinetics and Ca(2+) dependence of fusion, indicating that the mutations specifically affect the vesicle priming step. Mutation of a nearby tyrosine (Y337A), which interacts with closed syntaxin-1, mildly increased secretory amplitude. This correlated with results from an in vitro fusion assay probing the functions of Munc18-1, indicating an easier transition to the extended state in the mutant. Our findings support the notion that a conformational transition within the Munc18-1 domain 3a helix 12 leads to opening of a closed Munc18-1:syntaxin complex, followed by productive SNARE complex assembly and vesicle priming. SIGNIFICANCE STATEMENT: The essential postdocking role of Munc18-1 in vesicular exocytosis has remained elusive, but recent data led to the hypothesis that the extension of helix 12 in Munc18 within domain 3a leads to synaptobrevin-2/VAMP2 interaction and SNARE complex formation. Using both lack-of-function and gain-of-function mutants, we here report that the conformation of helix 12 predicts vesicle priming and secretory amplitude in living chromaffin cells. The effects of mutants on secretion could not be explained by differences in syntaxin-1 chaperoning/localization or vesicle docking, and the fusion kinetics and calcium dependence were unchanged, indicating that the effect of helix 12 extension is specific for the vesicle priming step. We conclude that a conformational change within helix 12 is responsible for the essential postdocking role of Munc18-1 in neurosecretion. PMID- 27358448 TI - Retinal Waves Modulate an Intraretinal Circuit of Intrinsically Photosensitive Retinal Ganglion Cells. AB - Before the maturation of rod and cone photoreceptors, the developing retina relies on light detection by intrinsically photosensitive retinal ganglion cells (ipRGCs) to drive early light-dependent behaviors. ipRGCs are output neurons of the retina; however, they also form functional microcircuits within the retina itself. Whether ipRGC microcircuits exist during development and whether they influence early light detection remain unknown. Here, we investigate the neural circuit that underlies the ipRGC-driven light response in developing mice. We use a combination of calcium imaging, tracer coupling, and electrophysiology experiments to show that ipRGCs form extensive gap junction networks that strongly contribute to the overall light response of the developing retina. Interestingly, we found that gap junction coupling was modulated by spontaneous retinal waves, such that acute blockade of waves dramatically increased the extent of coupling and hence increased the number of light-responsive neurons. Moreover, using an optical sensor, we found that this wave-dependent modulation of coupling is driven by dopamine that is phasically released by retinal waves. Our results demonstrate that ipRGCs form gap junction microcircuits during development that are modulated by retinal waves; these circuits determine the extent of the light response and thus potentially impact the processing of early visual information and light-dependent developmental functions. SIGNIFICANCE STATEMENT: Light-dependent functions in early development are mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). Here we show that ipRGCs form an extensive gap junction network with other retinal neurons, including other ipRGCs, which shapes the retina's overall light response. Blocking cholinergic retinal waves, which are the primary source of neural activity before maturation of photoreceptors, increased the extent of ipRGC gap junction networks, thus increasing the number of light-responsive cells. We determined that this modulation of ipRGC gap junction networks occurs via dopamine released by waves. These results demonstrate that retinal waves mediate dopaminergic modulation of gap junction networks to regulate pre-vision light responses. PMID- 27358449 TI - Differential Excitation of Distally versus Proximally Targeting Cortical Interneurons by Unitary Thalamocortical Bursts. AB - Thalamocortical neurons relay sensory and motor information to the neocortex using both single spikes and bursts; bursts prevail during low-vigilance states but also occur during awake behavior. Bursts are suggested to provide an alerting signal to the cortex and enhance stimulus detection, but the synaptic mechanisms underlying these effects are not clear, because the postsynaptic responses of different subtypes of cortical neurons to unitary thalamocortical bursts are mostly unknown. Using optogenetically guided recordings in mouse thalamocortical slices, we achieved the first reported paired intracellular recordings from nine monosynaptically connected thalamic and cortical neurons, including principal cells and two subtypes of inhibitory interneurons, and compared between cortical responses to single thalamocortical spikes and bursts. In 18 additional cortical neurons, we elicited unitary burst responses optogenetically. Short-term dynamics and temporal summation of burst-evoked EPSPs were cell-type dependent: in principal cells and somatostatin-containing (SOM), but not fast-spiking (FS), interneurons, peak response during a burst was on average more than twofold larger than the response to the first spike. Thus, firing a burst instead of a single spike would more than double the probability of firing in postsynaptic excitatory neurons and in SOM, but not FS, interneurons. Consistent with this prediction, FS interneurons held near firing threshold fired most often on the first burst component, whereas SOM interneurons fired only on the second or later components. By increasing excitation of principal cells together with SOM mediated, distally directed inhibition, thalamocortical bursts could momentarily enhance the saliency of the ascending sensory stimulus over less urgent, top-down inputs. SIGNIFICANCE STATEMENT: Thalamocortical neurons relay sensory and motor information to the cerebral cortex using both single spikes and high-frequency bursts, but the function of bursts is not fully understood. Using brain slices from mouse somatosensory thalamus and cortex, we achieved the first dual recordings of directly connected thalamic and cortical neurons and compared between cortical responses to single thalamic spikes and to bursts. We report that bursts enhanced the responses of excitatory neurons and of inhibitory interneurons that preferentially target dendrites. A potential consequence is that bursts will enhance the response to the immediate sensory event over responses to less urgent, modulatory inputs. PMID- 27358450 TI - The Dorsal Medial Prefrontal Cortex Responds Preferentially to Social Interactions during Natural Viewing. AB - Humans display a strong tendency to make spontaneous inferences concerning the thoughts and intentions of others. Although this ability relies upon the concerted effort of multiple brain regions, the dorsal medial prefrontal cortex (DMPFC) is most closely associated with the ability to reason about other people's mental states and form impressions of their character. Here, we investigated this region's putative social category preference using fMRI as 34 participants engaged in uninstructed viewing of a complex naturalistic stimulus. Using a data-driven "reverse correlation" approach, we characterize the DMPFC's stimulus response profile from ongoing neural responses to a dynamic movie stimulus. Results of this analysis demonstrate that the DMPFC's response profile is dominated by the presence of scenes involving social interactions between characters. Subsequent content analysis of video clips created from this response profile confirmed this finding. In contrast, regions of the inferotemporal and parietal cortex were selectively tuned to faces and actions, both features that often covary with social interaction but may be difficult to disentangle using standard event-related approaches. Together, these findings suggest that the DMPFC is finely tuned for processing social interaction above other categories and that this preference is maintained during unrestricted viewing of complex natural stimuli such as movies. SIGNIFICANCE STATEMENT: Recently, studies have brought into question whether the dorsal medial prefrontal cortex (DMPFC), a region long associated with social cognition, is specialized for the processing of social information. We examine the response profile of this region during natural viewing of a reasonably naturalistic stimulus (i.e., a Hollywood movie) using a data-driven reverse correlation technique. Our findings demonstrate that, during natural viewing, the DMPFC is strongly tuned to the social features of the stimulus above other categories. Moreover, this response differs from other areas with previously well characterized response profiles such as the lateral and medial fusiform gyrus. These findings suggest that this region's dominant function in everyday situations is to support reasoning about the thoughts and intentions of conspecifics. PMID- 27358451 TI - Enhanced Neuronal Activity in the Medial Prefrontal Cortex during Social Approach Behavior. AB - Although the medial prefrontal cortex (mPFC) is known to play a crucial role in rodent social behavior, little is known about mPFC neural correlates of social behavior. In the present study, we examined single-neuron activity in the mPFC of mice performing a modified version of the three-chamber test. We found that a subset of mPFC neurons elevate discharge rates when approaching a stranger mouse but not when approaching an inanimate object or an empty chamber. Our results reveal mPFC neural activity that is correlated with social approach behavior in a widely used social-interaction paradigm. These findings might be helpful for future investigations of mPFC neural processes underlying social interaction in health and disease. SIGNIFICANCE STATEMENT: Although the prefrontal cortex is known to play a crucial role in rodent social behavior, little is known about prefrontal neural correlates of social behavior. This study shows that the activity of a subset of prefrontal neurons increases in association with social approach behavior during a three-chamber test-a widely used behavioral paradigm. Such responses might be a signature of prefrontal neural processes underlying social approach behavior. PMID- 27358452 TI - Dynamic Modulation of Myelination in Response to Visual Stimuli Alters Optic Nerve Conduction Velocity. AB - Myelin controls the time required for an action potential to travel from the neuronal soma to the axon terminal, defining the temporal manner in which information is processed within the CNS. The presence of myelin, the internodal length, and the thickness of the myelin sheath are powerful structural factors that control the velocity and fidelity of action potential transmission. Emerging evidence indicates that myelination is sensitive to environmental experience and neuronal activity. Activity-dependent modulation of myelination can dynamically alter action potential conduction properties but direct functional in vivo evidence and characterization of the underlying myelin changes is lacking. We demonstrate that in mice long-term monocular deprivation increases oligodendrogenesis in the retinogeniculate pathway but shortens myelin internode lengths without affecting other structural properties of myelinated fibers. We also demonstrate that genetically attenuating synaptic glutamate neurotransmission from retinal ganglion cells phenocopies the changes observed after monocular deprivation, suggesting that glutamate may constitute a signal for myelin length regulation. Importantly, we demonstrate that visual deprivation and shortened internodes are associated with a significant reduction in nerve conduction velocity in the optic nerve. Our results reveal the importance of sensory input in the building of myelinated fibers and suggest that this activity dependent alteration of myelination is important for modifying the conductive properties of brain circuits in response to environmental experience. SIGNIFICANCE STATEMENT: Oligodendrocyte precursor cells differentiate into mature oligodendrocytes and are capable of ensheathing axons with myelin without molecular cues from neurons. However, this default myelination process can be modulated by changes in neuronal activity. Here, we show, for the first time, that experience-dependent activity modifies the length of myelin internodes along axons altering action potential conduction velocity. Such a mechanism would allow for variations in conduction velocities that provide a degree of plasticity in accordance to environmental needs. It will be important in future work to investigate how these changes in myelination and conduction velocity contribute to signal integration in postsynaptic neurons and circuit function. PMID- 27358453 TI - Gain in Body Fat Is Associated with Increased Striatal Response to Palatable Food Cues, whereas Body Fat Stability Is Associated with Decreased Striatal Response. AB - Cross-sectional brain-imaging studies reveal that obese versus lean humans show greater responsivity of reward and attention regions to palatable food cues, but lower responsivity of reward regions to palatable food receipt. However, these individual differences in responsivity may result from a period of overeating. We conducted a repeated-measures fMRI study to test whether healthy weight adolescent humans who gained body fat over a 2 or 3 year follow-up period show an increase in responsivity of reward and attention regions to a cue signaling impending milkshake receipt and a simultaneous decrease in responsivity of reward regions to milkshake receipt versus adolescents who showed stability of or loss of body fat. Adolescents who gained body fat, who largely remained in a healthy weight range, showed increases in activation in the putamen, mid-insula, Rolandic operculum, and precuneus to a cue signaling impending milkshake receipt versus those who showed stability of or loss of body fat, though these effects were partially driven by reductions in responsivity among the latter groups. Adolescents who gained body fat reported significantly greater milkshake wanting and milkshake pleasantness ratings at follow-up compared to those who lost body fat. Adolescents who gained body fat did not show a reduction in responsivity of reward regions to milkshake receipt or changes in responsivity to receipt and anticipated receipt of monetary reward. Data suggest that initiating a prolonged period of overeating may increase striatal responsivity to food cues, and that maintaining a balance between caloric intake and expenditure may reduce striatal, insular, and Rolandic operculum responsivity. SIGNIFICANCE STATEMENT: This novel, repeated-measures brain-imaging study suggests that adolescents who gained body fat over our follow-up period experienced an increase in striatal responsivity to cues for palatable foods compared to those who showed stability of or loss of body fat. Results also imply that maintaining a balance between caloric intake and expenditure over time may reduce striatal, insular, and Rolandic operculum responsivity to food cues, which might decrease risk for future overeating. PMID- 27358454 TI - Collective Activity of Many Bistable Assemblies Reproduces Characteristic Dynamics of Multistable Perception. AB - The timing of perceptual decisions depends on both deterministic and stochastic factors, as the gradual accumulation of sensory evidence (deterministic) is contaminated by sensory and/or internal noise (stochastic). When human observers view multistable visual displays, successive episodes of stochastic accumulation culminate in repeated reversals of visual appearance. Treating reversal timing as a "first-passage time" problem, we ask how the observed timing densities constrain the underlying stochastic accumulation. Importantly, mean reversal times (i.e., deterministic factors) differ enormously between displays/observers/stimulation levels, whereas the variance and skewness of reversal times (i.e., stochastic factors) keep characteristic proportions of the mean. What sort of stochastic process could reproduce this highly consistent "scaling property?" Here we show that the collective activity of a finite population of bistable units (i.e., a generalized Ehrenfest process) quantitatively reproduces all aspects of the scaling property of multistable phenomena, in contrast to other processes under consideration (Poisson, Wiener, or Ornstein-Uhlenbeck process). The postulated units express the spontaneous dynamics of attractor assemblies transitioning between distinct activity states. Plausible candidates are cortical columns, or clusters of columns, as they are preferentially connected and spontaneously explore a restricted repertoire of activity states. Our findings suggests that perceptual representations are granular, probabilistic, and operate far from equilibrium, thereby offering a suitable substrate for statistical inference. SIGNIFICANCE STATEMENT: Spontaneous reversals of high-level perception, so-called multistable perception, conform to highly consistent and characteristic statistics, constraining plausible neural representations. We show that the observed perceptual dynamics would be reproduced quantitatively by a finite population of distinct neural assemblies, each with locally bistable activity, operating far from the collective equilibrium (generalized Ehrenfest process). Such a representation would be consistent with the intrinsic stochastic dynamics of neocortical activity, which is dominated by preferentially connected assemblies, such as cortical columns or clusters of columns. We predict that local neuron assemblies will express bistable dynamics, with spontaneous active-inactive transitions, whenever they contribute to high-level perception. PMID- 27358455 TI - Effect of Rhodopsin Phosphorylation on Dark Adaptation in Mouse Rods. AB - Rhodopsin is a prototypical G-protein-coupled receptor (GPCR) that is activated when its 11-cis-retinal moiety is photoisomerized to all-trans retinal. This step initiates a cascade of reactions by which rods signal changes in light intensity. Like other GPCRs, rhodopsin is deactivated through receptor phosphorylation and arrestin binding. Full recovery of receptor sensitivity is then achieved when rhodopsin is regenerated through a series of steps that return the receptor to its ground state. Here, we show that dephosphorylation of the opsin moiety of rhodopsin is an extremely slow but requisite step in the restoration of the visual pigment to its ground state. We make use of a novel observation: isolated mouse retinae kept in standard media for routine physiologic recordings display blunted dephosphorylation of rhodopsin. Isoelectric focusing followed by Western blot analysis of bleached isolated retinae showed little dephosphorylation of rhodopsin for up to 4 h in darkness, even under conditions when rhodopsin was completely regenerated. Microspectrophotometeric determinations of rhodopsin spectra show that regenerated phospho-rhodopsin has the same molecular photosensitivity as unphosphorylated rhodopsin and that flash responses measured by trans-retinal electroretinogram or single-cell suction electrode recording displayed dark-adapted kinetics. Single quantal responses displayed normal dark adapted kinetics, but rods were only half as sensitive as those containing exclusively unphosphorylated rhodopsin. We propose a model in which light-exposed retinae contain a mixed population of phosphorylated and unphosphorylated rhodopsin. Moreover, complete dark adaptation can only occur when all rhodopsin has been dephosphorylated, a process that requires >3 h in complete darkness. SIGNIFICANCE STATEMENT: G-protein-coupled receptors (GPCRs) constitute the largest superfamily of proteins that compose ~4% of the mammalian genome whose members share a common membrane topology. Signaling by GPCRs regulate a wide variety of physiological processes, including taste, smell, hearing, vision, and cardiovascular, endocrine, and reproductive homeostasis. An important feature of GPCR signaling is its timely termination. This normally occurs when, after their activation, GPCRs are rapidly phosphorylated by specific receptor kinases and subsequently bound by cognate arrestins. Recovery of receptor sensitivity to the ground state then requires dephosphorylation of the receptor and unbinding of arrestin, processes that are poorly understood. Here we investigate in mouse rod photoreceptors the relationship between rhodopsin dephosphorylation and recovery of visual sensitivity. PMID- 27358456 TI - The Motor Cortex Is Involved in the Generation of Classically Conditioned Eyelid Responses in Behaving Rabbits. AB - Classical blink conditioning is a well known model for studying neural generation of acquired motor responses. The acquisition of this type of associative learning has been related to many cortical, subcortical, and cerebellar structures. However, until now, no one has studied the motor cortex (MC) and its possible role in classical eyeblink conditioning. We recorded in rabbits the activity of MC neurons during blink conditioning using a delay paradigm. Neurons were identified by their antidromic activation from facial nucleus (FN) or red nucleus (RN). For conditioning, we used a tone as a conditioned stimulus (CS) followed by an air puff as an unconditioned stimulus (US) that coterminated with it. Conditioned responses (CRs) were determined from the electromyographic activity of the orbicularis oculi muscle and/or from eyelid position recorded with the search coil technique. Type A neurons increased their discharge rates across conditioning sessions and reached peak firing during the CS-US interval, while type B cells presented a second peak during US presentation. Both of them project to the FN. Type C cells increased their firing across the CS-US interval, reaching peak values at the time of US presentation, and were activated from the RN. These three types of neurons fired well in advance of the beginning of CRs and changed with them. Reversible inactivation of the MC during conditioning evoked a decrease in learning curves and in the amplitude of CRs, while train stimulation of the MC simulated the profile and kinematics of conditioned blinks. In conclusion, MC neurons are involved in the acquisition and expression of CRs. SIGNIFICANCE STATEMENT: Classical blink conditioning is a popular experimental model for studying neural mechanisms underlying the acquisition of motor skills. The acquisition of this type of associative learning has been related to many cortical, subcortical, and cerebellar structures. However, until now, no one has studied the motor cortex (MC) and its possible role in classical eyeblink conditioning. Here, we report that the firing activities of MC neurons, recorded in behaving rabbits, are related to and preceded the initiation of conditioned blinks. MC neurons were identified as projecting to the red or facial nuclei and encoded the kinematics of conditioned eyelid responses. The timed stimulation of recording sites simulated the profile of conditioned blinks. MC neurons play a role in the acquisition and expression of these acquired motor responses. PMID- 27358457 TI - Tight Coupling of Astrocyte pH Dynamics to Epileptiform Activity Revealed by Genetically Encoded pH Sensors. AB - Astrocytes can both sense and shape the evolution of neuronal network activity and are known to possess unique ion regulatory mechanisms. Here we explore the relationship between astrocytic intracellular pH dynamics and the synchronous network activity that occurs during seizure-like activity. By combining confocal and two-photon imaging of genetically encoded pH reporters with simultaneous electrophysiological recordings, we perform pH measurements in defined cell populations and relate these to ongoing network activity. This approach reveals marked differences in the intracellular pH dynamics between hippocampal astrocytes and neighboring pyramidal neurons in rodent in vitro models of epilepsy. With three different genetically encoded pH reporters, astrocytes are observed to alkalinize during epileptiform activity, whereas neurons are observed to acidify. In addition to the direction of pH change, the kinetics of epileptiform-associated intracellular pH transients are found to differ between the two cell types, with astrocytes displaying significantly more rapid changes in pH. The astrocytic alkalinization is shown to be highly correlated with astrocytic membrane potential changes during seizure-like events and mediated by an electrogenic Na(+)/HCO3 (-) cotransporter. Finally, comparisons across different cell-pair combinations reveal that astrocytic pH dynamics are more closely related to network activity than are neuronal pH dynamics. This work demonstrates that astrocytes exhibit distinct pH dynamics during periods of epileptiform activity, which has relevance to multiple processes including neurometabolic coupling and the control of network excitability. SIGNIFICANCE STATEMENT: Dynamic changes in intracellular ion concentrations are central to the initiation and progression of epileptic seizures. However, it is not known how changes in intracellular H(+) concentration (ie, pH) differ between different cell types during seizures. Using recently developed pH-sensitive proteins, we demonstrate that astrocytes undergo rapid alkalinization during periods of seizure-like activity, which is in stark contrast to the acidification that occurs in neighboring neurons. Rapid astrocytic pH changes are highly temporally correlated with seizure activity, are mediated by an electrogenic Na(+)/HCO3- cotransporter, and are more tightly coupled to network activity than are neuronal pH changes. As pH has profound effects on signaling in the nervous system, this work has implications for our understanding of seizure dynamics. PMID- 27358458 TI - Kif1B Interacts with KBP to Promote Axon Elongation by Localizing a Microtubule Regulator to Growth Cones. AB - Delivery of proteins and organelles to the growth cone during axon extension relies on anterograde transport by kinesin motors. Though critical for neural circuit development, the mechanisms of cargo-specific anterograde transport during axon extension are only starting to be explored. Cargos of particular importance for axon outgrowth are microtubule modifiers, such as SCG10 (Stathmin 2). SCG10 is expressed solely during axon extension, localized to growth cones, and essential for axon outgrowth; however, the mechanisms of SCG10 transport and activity were still debated. Using zebrafish mutants and in vivo imaging, we identified the Kif1B motor and its interactor Kif1 binding protein (KBP) as critical for SCG10 transport to axon growth cones and complete axon extension. Axon truncation in kbp(st23) mutants can be suppressed by SCG10 overexpression, confirming the direct relationship between decreased SCG10 levels and failed axon outgrowth. Live imaging revealed that the reduced levels of SCG10 in kbp(st23) mutant growth cones led to altered microtubule stability, defining the mechanistic basis of axon truncation. Thus, our data reveal a novel role for the Kif1B-KBP complex in the anterograde transport of SCG10, which is necessary for proper microtubule dynamics and subsequent axon extension. SIGNIFICANCE STATEMENT: Together, our data define the mechanistic underpinnings of failed axon outgrowth with loss of KBP or its associated motor, Kif1B. In addition, we provide conclusive evidence that this defect results from disruption of anterograde transport of SCG10. This is one of the first examples of a motor to be implicated in the essential transport of a discreet cargo necessary for axon extension. In addition, counter to previous in vitro and cell culture results, neither loss of the Kif1B motor nor KBP resulted in inhibition of mitochondrial transport. Altogether, our work links transport of SCG10 to the regulation of microtubule dynamics in the axon growth cone and enhances our understanding of this process during axon outgrowth. PMID- 27358459 TI - Lasting Adaptations in Social Behavior Produced by Social Disruption and Inhibition of Adult Neurogenesis. AB - Research on social instability has focused on its detrimental consequences, but most people are resilient and respond by invoking various coping strategies. To investigate cellular processes underlying such strategies, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies. Social disruption produced a preference for familiar over novel conspecifics, a change that did not involve global memory impairments or increased anxiety. Using the neuropeptide oxytocin as a tool to increase neurogenesis in the hippocampus of disrupted rats restored preference for novel conspecifics to predisruption levels. Conversely, reducing the number of new neurons by limited inhibition of adult neurogenesis in naive transgenic GFAP-thymidine kinase rats resulted in social behavior similar to disrupted rats. Together, these results provide novel mechanistic evidence that social disruption shapes behavior in a potentially adaptive way, possibly by reducing adult neurogenesis in the hippocampus. SIGNIFICANCE STATEMENT: To investigate cellular processes underlying adaptation to social instability, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies. Unexpectedly, these changes were accompanied by changes in social strategies without evidence of impairments in cognition or anxiety regulation. Restoring adult neurogenesis in disrupted rats using oxytocin and conditionally suppressing the production of new neurons in socially naive GFAP-thymidine kinase rats showed that loss of 6-week-old neurons may be responsible for adaptive changes in social behavior. PMID- 27358460 TI - Developmental Switch in Spike Timing-Dependent Plasticity and Cannabinoid Dependent Reorganization of the Thalamocortical Projection in the Barrel Cortex. AB - The formation and refinement of thalamocortical axons (TCAs) is an activity dependent process (Katz and Shatz, 1996), but its mechanism and nature of activity are elusive. We studied the role of spike timing-dependent plasticity (STDP) in TCA formation and refinement in mice. At birth (postnatal day 0, P0), TCAs invade the cortical plate, from which layers 4 (L4) and L2/3 differentiate at P3-P4. A portion of TCAs transiently reach toward the pia surface around P2-P4 (Senft and Woolsey, 1991; Rebsam et al., 2002) but are eventually confined below the border between L2/3 and L4. We previously showed that L4-L2/3 synapses exhibit STDP with only potentiation (timing-dependent long-term potentiation [t LTP]) during synapse formation, then switch to a Hebbian form of STDP. Here we show that TCA-cortical plate synapses exhibit robust t-LTP in neonates, whose magnitude decreased gradually after P4-P5. After L2/3 is differentiated, TCA-L2/3 gradually switched to STDP with only depression (t-LTD) after P7-P8, whereas TCA L4 lost STDP. t-LTP was dependent on NMDA receptor and PKA, whereas t-LTD was mediated by Type 1 cannabinoid receptors (CB1Rs) probably located at TCA terminals, revealed by global and cortical excitatory cell-specific knock-out of CB1R. Moreover, we found that administration of CB1R agonists, including Delta(9) tetrahydrocannabinol, caused substantial retraction of TCAs. Consistent with this, individual thalamocortical axons exuberantly innervated L2/3 at P12 in CB1R knock-outs, indicating that endogenous cannabinoid signaling shapes TCA projection. These results suggest that the developmental switch in STDP and associated appearance of CB1R play important roles in the formation and refinement of TCAs. SIGNIFICANCE STATEMENT: It has been shown that neural activity is required for initial synapse formation of thalamocortical axons with cortical cells, but precisely what sort of activities in presynaptic and postsynaptic cells are required is not yet clear. In addition, how activity is further translated into structural changes is unclear. We show here that the period during which spike timing-dependent long-term potentiation and depression (t-LTP, t-LTD) can be induced closely matches the time course of synapse formation and retraction, respectively, at the thalamocortical synapse. Moreover, administration of cannabinoid agonists, which mimic t-LTD, caused TCA retraction, suggesting that cannabinoids translate physiological changes into morphological consequences. PMID- 27358462 TI - Implications of Lateral Cerebellum in Proactive Control of Saccades. AB - Although several lines of evidence establish the involvement of the medial and vestibular parts of the cerebellum in the adaptive control of eye movements, the role of the lateral hemisphere of the cerebellum in eye movements remains unclear. Ascending projections from the lateral cerebellum to the frontal and parietal association cortices via the thalamus are consistent with a role of these pathways in higher-order oculomotor control. In support of this, previous functional imaging studies and recent analyses in subjects with cerebellar lesions have indicated a role for the lateral cerebellum in volitional eye movements such as anti-saccades. To elucidate the underlying mechanisms, we recorded from single neurons in the dentate nucleus of the cerebellum in monkeys performing anti-saccade/pro-saccade tasks. We found that neurons in the posterior part of the dentate nucleus showed higher firing rates during the preparation of anti-saccades compared with pro-saccades. When the animals made erroneous saccades to the visual stimuli in the anti-saccade trials, the firing rate during the preparatory period decreased. Furthermore, local inactivation of the recording sites with muscimol moderately increased the proportion of error trials, while successful anti-saccades were more variable and often had shorter latency during inactivation. Thus, our results show that neuronal activity in the cerebellar dentate nucleus causally regulates anti-saccade performance. Neuronal signals from the lateral cerebellum to the frontal cortex might modulate the proactive control signals in the corticobasal ganglia circuitry that inhibit early reactive responses and possibly optimize the speed and accuracy of anti saccades. SIGNIFICANCE STATEMENT: Although the lateral cerebellum is interconnected with the cortical eye fields via the thalamus and the pons, its role in eye movements remains unclear. We found that neurons in the caudal part of the lateral (dentate) nucleus of the cerebellum showed the increased firing rate during the preparation of anti-saccades. Inactivation of the recording sites modestly elevated the rate of erroneous saccades to the visual stimuli in the anti-saccade trials, while successful anti-saccades during inactivation tended to have a shorter latency. Our data indicate that neuronal signals in the lateral cerebellum may proactively regulate anti-saccade generation through the pathways to the frontal cortex, and may inhibit early reactive responses and regulate the accuracy of anti-saccades. PMID- 27358461 TI - Poststroke Induction of alpha-Synuclein Mediates Ischemic Brain Damage. AB - alpha-Synuclein (alpha-Syn), one of the most abundant proteins in the CNS, is known to be a major player in the neurodegeneration observed in Parkinson's disease. We currently report that transient focal ischemia upregulates alpha-Syn protein expression and nuclear translocation in neurons of the adult rodent brain. We further show that knockdown or knock-out of alpha-Syn significantly decreases the infarction and promotes better neurological recovery in rodents subjected to focal ischemia. Furthermore, alpha-Syn knockdown significantly reduced postischemic induction of phospho-Drp1, 3-nitrotyrosine, cleaved caspase 3, and LC-3 II/I, indicating its role in modulating mitochondrial fragmentation, oxidative stress, apoptosis, and autophagy, which are known to mediate poststroke neuronal death. Transient focal ischemia also significantly upregulated serine 129 (S129) phosphorylation (palpha-Syn) of alpha-Syn and nuclear translocation of palpha-Syn. Furthermore, knock-out mice that lack PLK2 (the predominant kinase that mediates S129 phosphorylation) showed better functional recovery and smaller infarcts when subjected to transient focal ischemia, indicating a detrimental role of S129 phosphorylation of alpha-Syn. In conclusion, our studies indicate that alpha-Syn is a potential therapeutic target to minimize poststroke brain damage. SIGNIFICANCE STATEMENT: Abnormal aggregation of alpha-synuclein (alpha Syn) has been known to cause Parkinson's disease and other chronic synucleinopathies. However, even though alpha-Syn is linked to pathophysiological mechanisms similar to those that produce acute neurodenegerative disorders, such as stroke, the role of alpha-Syn in such disorder is not clear. We presently studied whether alpha-Syn mediates poststroke brain damage and more importantly whether preventing alpha-Syn expression is neuroprotective and leads to better physiological and functional outcome after stroke. Our study indicates that alpha Syn is a potential therapeutic target for stroke therapy. PMID- 27358463 TI - Stimulation of Bovine Whole-Blood Samples Cultured in Media Supplemented with Recombinant Interleukin-7 (IL-7) and IL-12 Extends the Life Span of the Gamma Interferon Assay To Detect Mycobacterium bovis-Infected Cattle. AB - The gamma interferon (IFN-gamma) assay is widely used to measure cell-mediated immune (CMI) response for the early detection of tuberculosis infection. Processing whole-blood samples for CMI-based diagnostics is time sensitive and usually must occur within 8 h of collection to ensure optimal assay performance. In this study, we developed and tested a modified protocol, in which whole-blood samples from Mycobacterium bovis-infected cattle were diluted 1:1 in RPMI medium containing 0.3% fetal bovine serum (FBS) added or not to recombinant mouse interleukin-7 (rmIL-7) or rmIL-12, alone or in combination, and stored at 4 degrees C. At 3 and 6 days postcollection, the diluted blood samples were adjusted to 10% FBS, dispensed into culture trays, stimulated with a bovine purified protein derivative from M. bovis, and incubated at 37 degrees C in 5% CO2 in air. Plasma was removed and assayed for an IFN-gamma response using bovine IFN-gamma enzyme-linked immunosorbent assay (ELISA) (Bovigam). The results were then compared with those obtained from the conventional procedure. The IFN-gamma responses of the samples stored up to 6 days postcollection in the supplemented RPMI medium were similar to those observed in the samples processed within 8 h after sampling, indicating that lymphocyte vitality and response were preserved. The addition of rmIL-7 and rmIL-12, alone or in combination, to culture medium can enhance lymphocyte survival and thus extends the time limit within which the IFN-gamma assay can be applied as a diagnostic tool in bovine tuberculosis surveillance and eradication. PMID- 27358464 TI - Multicenter Evaluation of the Solana Group A Streptococcus Assay: Comparison with Culture. AB - We compared group A Streptococcus (GAS) culture with a rapid helicase-dependent amplification (HDA) method using 1,082 throat swab specimens. The HDA method demonstrated 98.2% sensitivity and 97.2% specificity. GAS prevalence by culture was 20.7%, and it was 22.6% using the HDA method. In 35 min, the HDA method provided rapid, sensitive GAS detection, making culture confirmation unnecessary. PMID- 27358465 TI - Whole-Genome Sequencing Elucidates Epidemiology of Nosocomial Clusters of Acinetobacter baumannii. AB - We characterized two epidemiologically similar Acinetobacter baumannii clusters from two separate intensive care units (ICU) using core genome multilocus sequence typing. Clonal spread was confirmed in ICU-1 (12 of 14 isolates shared genotypes); in ICU-2, all genotypes (13 isolates) were diverse, thus excluding transmissions and enabling adequate infection control measures. PMID- 27358466 TI - Development of a Real-Time PCR Protocol Requiring Minimal Handling for Detection of Vancomycin-Resistant Enterococci with the Fully Automated BD Max System. AB - Vancomycin-resistant enterococci (VRE) are an important cause of health care associated infections, resulting in significant mortality and a significant economic burden in hospitals. Active surveillance for at-risk populations contributes to the prevention of infections with VRE. The availability of a combination of automation and molecular detection procedures for rapid screening would be beneficial. Here, we report on the development of a laboratory-developed PCR for detection of VRE which runs on the fully automated Becton Dickinson (BD) Max platform, which combines DNA extraction, PCR setup, and real-time PCR amplification. We evaluated two protocols: one using a liquid master mix and the other employing commercially ordered dry-down reagents. The BD Max VRE PCR was evaluated in two rounds with 86 and 61 rectal elution swab (eSwab) samples, and the results were compared to the culture results. The sensitivities of the different PCR formats were 84 to 100% for vanA and 83.7 to 100% for vanB; specificities were 96.8 to 100% for vanA and 81.8 to 97% for vanB The use of dry down reagents and the ExK DNA-2 kit for extraction showed that the samples were less inhibited (3.3%) than they were by the use of the liquid master mix (14.8%). Adoption of a cutoff threshold cycle of 35 for discrimination of vanB-positive samples allowed an increase of specificity to 87.9%. The performance of the BD Max VRE assay equaled that of the BD GeneOhm VanR assay, which was run in parallel. The use of dry-down reagents simplifies the assay and omits any need to handle liquid PCR reagents. PMID- 27358467 TI - Newly Identified Enterovirus C Genotypes, Identified in the Netherlands through Routine Sequencing of All Enteroviruses Detected in Clinical Materials from 2008 to 2015. AB - Enteroviruses (EVs) are a group of human and animal viruses that are capable of causing a variety of clinical syndromes. Different genotypes classified into species can be distinguished on the basis of sequence divergence in the VP1 capsid-coding region. Apparently new genotypes are discovered regularly, often as incidental findings in studies investigating respiratory syndromes or as part of poliovirus surveillance. Recently, some EVs have become recognized as significant respiratory pathogens, and a number of new genotypes belonging to species C have been identified. The circulation of these newly identified species C EVs, such as EV-C104, EV-C105, EV-C109, and EV-C117, nevertheless appears to be limited. In this report, we show the results of routine genotyping of all enteroviruses detected in our tertiary care hospital between January 2008 and April 2015. We detected 365 EVs belonging to 40 genotypes. Interestingly, several newly identified species C EVs were detected during the study period. Sequencing of the 5' untranslated region (5' UTR) of these viruses shows divergence in this region, which is a target region in many detection assays. PMID- 27358468 TI - Evaluation of Elecsys Syphilis Assay for Routine and Blood Screening and Detection of Early Infection. AB - Treponema pallidum infections can have severe complications if not diagnosed and treated at an early stage. Screening and diagnosis of syphilis require assays with high specificity and sensitivity. The Elecsys Syphilis assay is an automated treponemal immunoassay for the detection of antibodies against T. pallidum The performance of this assay was investigated previously in a multicenter study. The current study expands on that evaluation in a variety of diagnostic settings and patient populations, at seven independent laboratories. The samples included routine diagnostic samples, blood donation samples, samples from patients with confirmed HIV infections, samples from living organ or bone marrow donors, and banked samples, including samples previously confirmed as syphilis positive. This study also investigated the seroconversion sensitivity of the assay. With a total of 1,965 syphilis-negative routine diagnostic samples and 5,792 syphilis-negative samples collected from blood donations, the Elecsys Syphilis assay had specificity values of 99.85% and 99.86%, respectively. With 333 samples previously identified as syphilis positive, the sensitivity was 100% regardless of disease stage. The assay also showed 100% sensitivity and specificity with samples from 69 patients coinfected with HIV. The Elecsys Syphilis assay detected infection in the same bleed or earlier, compared with comparator assays, in a set of sequential samples from a patient with primary syphilis. In archived serial blood samples collected from 14 patients with direct diagnoses of primary syphilis, the Elecsys Syphilis assay detected T. pallidum antibodies for 3 patients for whom antibodies were not detected with the Architect Syphilis TP assay, indicating a trend for earlier detection of infection, which may have the potential to shorten the time between infection and reactive screening test results. PMID- 27358469 TI - Colonisation with methicillin-resistant Staphylococcus aureus and associated factors among nurses with occupational skin diseases. AB - OBJECTIVES: To evaluate the prevalence of colonisation with methicillin-resistant Staphylococcus aureus (MRSA), associated factors and the effectiveness of decolonisation procedures among nurses with occupational skin diseases (OSD). METHODS: In a retrospective cohort study, the medical records of 319 nurses from Germany who were screened consecutively for MRSA when participating in a tertiary individual prevention programme (TIP) for severe OSD between July 2009 and December 2014 were evaluated. RESULTS: 90.3% of nurses with severe OSD suffered from hand eczema. 43 were colonised with MRSA on admission (13.5%), mainly in the nose (n=35, 81.4%). However, the hands were affected in more than half of the MRSA carriers (n=24, 55.8%). Risk factors for MRSA colonisation were atopic skin diathesis (OR 2.01, 95% CI 1.03 to 3.92, p=0.049) and presence of atopic dermatitis on other body parts than the hands (OR 4.33, 95% CI 2.23 to 8.43, p<0.001). Hand eczema was significantly more severe in MRSA carriers than in non carriers (OR 1.23, 95% CI 1.10 to 1.37, p<0.001) and showed a higher prevalence of vesicles, erosions or fissures. MRSA eradication was successful in 67.4% after the first attempt. CONCLUSIONS: Nurses with OSD have a twofold to threefold higher prevalence of MRSA colonisation than what has been reported for point prevalence screenings among healthcare workers in Germany. Atopic skin diathesis, atopic dermatitis and severe hand eczema are the main risk factors. Thus, prevention and treatment of OSD could be important elements in reduction of colonisation with MRSA among nurses and transmission to others. PMID- 27358470 TI - Bioenergetic and volume regulatory effects of mitoKATP channel modulators protect against hypoxia-reoxygenation-induced mitochondrial dysfunction. AB - The mitochondrial ATP-sensitive K(+) (mitoKATP) channel plays a significant role in mitochondrial physiology and protects against ischemic reperfusion injury in mammals. Although fish frequently face oxygen fluctuations in their environment, the role of the mitoKATP channel in regulating the responses to oxygen stress is rarely investigated in this class of animals. To elucidate whether and how the mitoKATP channel protects against hypoxia-reoxygenation (H-R)-induced mitochondrial dysfunction in fish, we first determined the mitochondrial bioenergetic effects of two key modulators of the channel, diazoxide and 5 hydroxydecanoate (5-HD), using a wide range of doses. Subsequently, the effects of low and high doses of the modulators on mitochondrial bioenergetics and volume under normoxia and after H-R using buffers with and without magnesium and ATP (Mg ATP) were tested. In the absence of Mg-ATP (mitoKATP channel open), both low and high doses of diazoxide improved mitochondrial coupling, but only the high dose of 5-HD reversed the post-H-R coupling-enhancing effect of diazoxide. In the presence of Mg-ATP (mitoKATP channel closed), diazoxide at the low dose improved coupling post-H-R, and this effect was abolished by 5-HD at the low dose. Interestingly, both low and high doses of diazoxide reversed H-R-induced swelling under mitoKATP channel open conditions, but this effect was not sensitive to 5 HD. Under mitoKATP channel closed conditions, diazoxide at the low dose protected the mitochondria from H-R-induced swelling and 5-HD at the low dose reversed this effect. In contrast, diazoxide at the high dose failed to reduce the swelling caused by H-R, and the addition of the high dose of 5-HD enhanced mitochondrial swelling. Overall, our study showed that in the presence of Mg-ATP, both opening of mitoKATP channels and bioenergetic effects of diazoxide were protective against H-R in fish mitochondria, while in the absence of Mg-ATP only the bioenergetic effect of diazoxide was protective. PMID- 27358471 TI - The orphan pentameric ligand-gated ion channel pHCl-2 is gated by pH and regulates fluid secretion in Drosophila Malpighian tubules. AB - Pentameric ligand-gated ion channels (pLGICs) constitute a large protein superfamily in metazoa whose role as neurotransmitter receptors mediating rapid, ionotropic synaptic transmission has been extensively studied. Although the vast majority of pLGICs appear to be neurotransmitter receptors, the identification of pLGICs in non-neuronal tissues and homologous pLGIC-like proteins in prokaryotes points to biological functions, possibly ancestral, that are independent of neuronal signalling. Here, we report the molecular and physiological characterization of a highly divergent, orphan pLGIC subunit encoded by the pHCl 2 (CG11340) gene, in Drosophila melanogaster We show that pHCl-2 forms a channel that is insensitive to a wide array of neurotransmitters, but is instead gated by changes in extracellular pH. pHCl-2 is expressed in the Malpighian tubules, which are non-innervated renal-type secretory tissues. We demonstrate that pHCl-2 is localized to the apical membrane of the epithelial principal cells of the tubules and that loss of pHCl-2 reduces urine production during diuresis. Our data implicate pHCl-2 as an important source of chloride conductance required for proper urine production, highlighting a novel role for pLGICs in epithelial tissues regulating fluid secretion and osmotic homeostasis. PMID- 27358472 TI - Patterns of variation in feeding strike kinematics of juvenile ghost praying mantis (Phyllocrania paradoxa): are components of the strike stereotypic? AB - Functional systems, such as feeding mechanics, often involve the evolution of several components of the musculoskeletal system that are moved in coordination to capture prey. Because these systems often involve the quick movement of several structures, some feeding systems have been hypothesized to be stereotypic. While the motor activity patterns are often stereotyped, the subsequent kinematics can be variable, many times in response to variation in prey stimulus (e.g. prey position). Patterns of feeding kinematics have been well studied among vertebrates, with less attention on invertebrate systems. The goal of this study was to examine the amount of stereotypy in the feeding strike kinematics of praying mantises. We filmed eight juvenile ghost praying mantises (Phyllocrania paradoxa) at 1000 Hz across several days within instar 7. We digitized several points that represent the movement of the coxa, trochanter femur and tibia of the raptorial foreleg to obtain a set of kinematics including angles and angular velocities of the joint, as well as body lunge. Using the coefficient of variation, we found less stereotypy in the approach stage of the strike compared with the sweep. Using Bonferroni-corrected Pearson's correlations of kinematics with prey position, we found few traits related to prey position with the exception of some kinematics of the coxa joint and the amount of lunge used during the strike. Our results suggest that several components of the praying mantis strike are stereotypic, while others exhibit flexibility to ensure successful capture of the prey. PMID- 27358473 TI - Pediatric Resident Workload Intensity and Variability. AB - BACKGROUND: Research on resident workloads has focused primarily on the quantity of hours worked, rather than the content of those hours or the variability among residents. We hypothesize that there are statistically significant variations in resident workloads and better understanding of workload intensity could improve resident education. METHODS: The Stanford Children's Health research database was queried for all electronic notes and orders written by pediatric residents from June 2012 to March 2014. The dataset was narrowed to ensure an accurate comparison among residents. A survey was used to determine residents' self perceived workload intensity. Variability of total notes written and orders entered was analyzed by chi(2) test and a Monte Carlo simulation. Linear regression was used to analyze the correlation between note-writing and order entry workload intensity. RESULTS: A total of 20 280 notes and 112 214 orders were written by 26 pediatric interns during 6 core rotations between June 2012 and June 2013. Both order-entry and note-writing workload intensity showed highly significant (P < .001) variability among residents. "High workload" residents, defined as the top quartile of total workload intensity, wrote 91% more orders and 19% more notes than "low workload" residents in the bottom quartile. Statistically significant correlation was observed between note-writing and order entry workload intensity (R(2) = 0.22; P = .02). There was no significant correlation between residents' self-perceived workload intensity and their objective workload. CONCLUSIONS: Significant variations in workload exist among pediatric residents. This may contribute to heterogeneous educational opportunities, physician wellness, and quality of patient care. PMID- 27358474 TI - Characteristics of Children and Adolescents With Multiple Sclerosis. AB - OBJECTIVES: To describe the demographic and clinical characteristics of pediatric multiple sclerosis (MS) in the United States. METHODS: This prospective observational study included children and adolescents with MS. Cases were evaluated across 9 geographically diverse sites as part of the US Network of Pediatric MS Centers. RESULTS: A total of 490 children and adolescents (324 girls, 166 boys) were enrolled; 28% developed symptoms before 12 years of age. The proportion of girls increased with age from 58% (<12 years) to 70% (>=12 years). Race and ethnicity as self-identified were: white, 67%; African American, 21%; and non-Hispanic, 70%. Most (94%) of the cases were born in the United States, and 39% had 1 or both foreign-born parents. Fifty-five percent of cases had a monofocal presentation; 31% had a prodrome (most frequently infectious), most often among those aged <12 years (P < .001). Children aged <12 years presented more commonly with encephalopathy and coordination problems (P < .001). Sensory symptoms were more frequently reported by older children (ie, those aged >=12 years) (P < .001); 78% of girls had MS onset postmenarche. The initial Expanded Disability Status Scale score for the group was <3.0, and the annualized relapse rate was 0.647 for the first 2 years. Interval from symptom onset to diagnosis and from diagnosis to initiation of disease-modifying therapy was longer among those <12 years of age. CONCLUSIONS: Pediatric MS in the United States is characterized by racial and ethnic diversity, a high proportion of children with foreign-born parents, and differences in clinical features and timing of treatment among those <12 years of age compared with older children. PMID- 27358475 TI - Parental Country of Birth and Childhood Vaccination Uptake in Washington State. AB - BACKGROUND: Underimmunization of certain immigrant populations can place them at high risk of experiencing vaccine-preventable disease outbreaks. METHODS: We conducted a retrospective cohort study between January 1, 2008, and May 1, 2013, among children included in the Washington State Immunization Information System. We assessed receipt of 1 or more doses of measles-containing, hepatitis A, pneumococcal, and diphtheria-tetanus-acellular pertussis-containing vaccines between 12 and 23 months of age. We compared children with 1 or more parents born in Somalia, Ukraine, Russia, Mexico, or India to children with 2 parents born in the United States. Poisson regression models with robust SEs were used to provide prevalence ratios adjusted for maternal education and number of prenatal visits. RESULTS: We identified 277 098 children, including 65 466 with foreign-born parents. Children of Somali-born parents were less likely to be immunized against measles than children of US-born parents (prevalence ratio: 0.82; 95% confidence interval: 0.80-0.84); this decrease became more pronounced over time (P < .01). No such disparity between these groups was observed with other vaccines. Compared with children of US-born parents, children of Ukrainian-born and Russian-born parents were less likely to be immunized, whereas children of Mexican-born and Indian-born parents were more likely to be immunized with any of the specified vaccines. CONCLUSIONS: We found country-specific patterns of immunization that may reflect underlying cultural or other beliefs. Certain immigrant communities with higher rates of immunization refusal may be at risk for vaccine-preventable diseases and require new forms of public health outreach. PMID- 27358476 TI - Self-Fertilization and the Role of Males in Populations of Tadpole Shrimp (Branchiopoda: Notostraca: Triops). AB - Self-fertilization has both negative and positive fitness effects on species evolution. Selfing can increase inbreeding depression, thereby decreasing genetic diversity. In contrast, self-fertilization can preserve beneficial gene combinations and facilitate colonization success. Within the class of crustaceans Branchiopoda, selfing is a primary reproductive mode. Some species of Triops, in the family Notostraca, are a few of the animal species thought to have a mixed mating system between hermaphrodites and males termed androdioecy. The objective of this study is to validate the reproductive mode utilized by Triops newberryi in southern New Mexico by the use of progeny arrays and population simulations. Individuals were reared in the lab from dried soil collected from temporary ponds inhabited by T. newberryi The adults reared and the encysted embryos contained within their brood pouches were genotyped using 7 T. newberryi specific microsatellite markers to determine the relatedness between parent and offspring. Overall microsatellite diversity was low with few heterozygous individuals and limited polymorphisms. Simulated populations and allele segregation analysis suggest hermaphroditism is the primary reproductive mode for T. newberryi In addition, based on the offspring's alleles, there was no direct evidence that a male (ovisacless) T. newberryi outcrossed with a female. Population simulations further suggest that the rate of successful outcrossing events must be low and could explain why outcrossing was not observed in the laboratory rearing trials. PMID- 27358477 TI - Necrotic pyknosis is a morphologically and biochemically distinct event from apoptotic pyknosis. AB - Classification of apoptosis and necrosis by morphological differences has been widely used for decades. However, this usefulness of this method has been seriously questioned in recent years, mainly due to a lack of functional and biochemical evidence to interpret the morphology changes. To address this matter, we devised genetic manipulations in Drosophila to study pyknosis, a process of nuclear shrinkage and chromatin condensation that occurs in apoptosis and necrosis. By following the progression of necrotic pyknosis, we surprisingly observed a transient state of chromatin detachment from the nuclear envelope, followed by the nuclear envelope completely collapsing onto chromatin. This phenomenon led us to discover that phosphorylation of barrier-to-autointegration factor (BAF) mediates this initial separation of nuclear envelope from chromatin. Functionally, inhibition of BAF phosphorylation suppressed necrosis in both Drosophila and human cells, suggesting that necrotic pyknosis is conserved in the propagation of necrosis. In contrast, during apoptotic pyknosis the chromatin did not detach from the nuclear envelope and inhibition of BAF phosphorylation had no effect on apoptotic pyknosis and apoptosis. Our research provides the first genetic evidence supporting a morphological classification of apoptosis and necrosis through different forms of pyknosis. PMID- 27358478 TI - Morphological process of podocyte development revealed by block-face scanning electron microscopy. AB - Podocytes present a unique 3D architecture specialized for glomerular filtration. However, several 3D morphological aspects on podocyte development remain partially understood because they are difficult to reveal using conventional scanning electron microscopy (SEM). Here, we adopted serial block-face SEM imaging, a powerful tool for analyzing the 3D cellular ultrastructure, to precisely reveal the morphological process of podocyte development, such as the formation of foot processes. Development of foot processes gives rise to three morphological states: the primitive, immature and mature foot processes. Immature podocytes were columnar in shape and connected to each other by the junctional complex, which migrated toward the basal side of the cell. When the junctional complex was close to the basement membrane, immature podocytes started to interdigitate with primitive foot processes under the level of junctional complex. As primitive foot processes lengthened, the junctional complex moved between primitive foot processes to form immature foot processes. Finally, the junctional complex was gradually replaced by the slit diaphragm, resulting in the maturation of immature foot processes into mature foot processes. In conclusion, the developmental process of podocytes is now clearly visualized by block-face SEM imaging. PMID- 27358480 TI - Numb directs the subcellular localization of EAAT3 through binding the YxNxxF motif. AB - Excitatory amino acid transporter type 3 (EAAT3, also known as SLC1A1) is a high affinity, Na(+)-dependent glutamate carrier that localizes primarily within the cell and at the apical plasma membrane. Although previous studies have reported proteins and sequence regions involved in EAAT3 trafficking, the detailed molecular mechanism by which EAAT3 is distributed to the correct location still remains elusive. Here, we identify that the YVNGGF sequence in the C-terminus of EAAT3 is responsible for its intracellular localization and apical sorting in rat hepatoma cells CRL1601 and Madin-Darby canine kidney (MDCK) cells, respectively. We further demonstrate that Numb, a clathrin adaptor protein, directly binds the YVNGGF motif and regulates the localization of EAAT3. Mutation of Y503, N505 and F508 within the YVNGGF motif to alanine residues or silencing Numb by use of small interfering RNA (siRNA) results in the aberrant localization of EAAT3. Moreover, both Numb and the YVNGGF motif mediate EAAT3 endocytosis in CRL1601 cells. In summary, our study suggests that Numb is a pivotal adaptor protein that mediates the subcellular localization of EAAT3 through binding the YxNxxF (where x stands for any amino acid) motif. PMID- 27358479 TI - The Src kinases Hck, Fgr and Lyn activate Arg to facilitate IgG-mediated phagocytosis and Leishmania infection. AB - Leishmaniasis is a devastating disease that disfigures or kills nearly two million people each year. Establishment and persistence of infection by the obligate intracellular parasite Leishmania requires repeated uptake by macrophages and other phagocytes. Therefore, preventing uptake could be a novel therapeutic strategy for leishmaniasis. Amastigotes, the life cycle stage found in the human host, bind Fc receptors and enter macrophages primarily through immunoglobulin-mediated phagocytosis. However, the host machinery that mediates amastigote uptake is poorly understood. We have previously shown that the Arg (also known as Abl2) non-receptor tyrosine kinase facilitates L. amazonensis amastigote uptake by macrophages. Using small-molecule inhibitors and primary macrophages lacking specific Src family kinases, we now demonstrate that the Hck, Fgr and Lyn kinases are also necessary for amastigote uptake by macrophages. Src mediated Arg activation is required for efficient uptake. Interestingly, the dual Arg and Src kinase inhibitor bosutinib, which is approved to treat cancer, not only decreases amastigote uptake, but also significantly reduces disease severity and parasite burden in Leishmania-infected mice. Our results suggest that leishmaniasis could potentially be treated with host-cell-active agents such as kinase inhibitors. PMID- 27358481 TI - Oocyte-dependent activation of MTOR in cumulus cells controls the development and survival of cumulus-oocyte complexes. AB - Communication between oocytes and their companion somatic cells promotes the healthy development of ovarian follicles, which is crucial for producing oocytes that can be fertilized and are competent to support embryogenesis. However, how oocyte-derived signaling regulates these essential processes remains largely undefined. Here, we demonstrate that oocyte-derived paracrine factors, particularly GDF9 and GDF9-BMP15 heterodimer, promote the development and survival of cumulus-cell-oocyte complexes (COCs), partly by suppressing the expression of Ddit4l, a negative regulator of MTOR, and enabling the activation of MTOR signaling in cumulus cells. Cumulus cells expressed less Ddit4l mRNA and protein than mural granulosa cells, which is in striking contrast to the expression of phosphorylated RPS6 (a major downstream effector of MTOR). Knockdown of Ddit4l activated MTOR signaling in cumulus cells, whereas inhibition of MTOR in COCs compromised oocyte developmental competence and cumulus cell survival, with the latter likely to be attributable to specific changes in a subset of transcripts in the transcriptome of COCs. Therefore, oocyte suppression of Ddit4l expression allows for MTOR activation in cumulus cells, and this oocyte dependent activation of MTOR signaling in cumulus cells controls the development and survival of COCs. PMID- 27358482 TI - Spinal Neuronal NOS Signaling Contributes to Morphine Cardioprotection in Ischemia Reperfusion Injury in Rats. AB - Morphine has been widely used as rescue treatment for heart attack and failure in humans for many decades. Relatively little has been known about the role of spinal opioid receptors in morphine cardioprotection. Recent studies have shown that intrathecal injection of morphine can reduce the heart injury caused by ischemia (I)/reperfusion (R) in rats. However, the molecular and cellular mechanisms underlying intrathecal morphine cardioprotection has not been determined. Here, we report that intrathecal morphine postconditioning (IMPOC) rescued mean artery pressure (MAP) and reduced myocardial injury in I/R. Pretreatment with either naloxone (NAL), a selective mu-opioid receptor antagonist, or nitric oxide synthase (NOS) inhibitors via intrathecal delivery completely abolished IMPOC cardioprotection, suggesting that the spinal mu-opioid receptor and its downstream NOS signaling pathway are involved in the mechanism of the morphine-induced effect. Consistent with this, IMPOC significantly enhanced spinal neural NOS phosphorylation, nitric oxide, and cGMP content in a similar time course. Intrathecal application of 1H-[1,2,4]oxadiazolo[4,3 a]quinoxalin-1-one, a specific inhibitor of guanylate cyclase, completely ablated IMPOC-induced enhancement of cardioprotection and spinal cGMP content. IMPOC rescue of MAP and ischemic injury is correlated with IMPOC enhancement of NOS signaling. Collectively, these findings strengthen the concept of spinal mu opioid receptors as a therapeutic target that mediates morphine-induced cardioprotection. We also provide evidence suggesting that the activation of spinal NOS signaling is essential for morphine cardioprotection. PMID- 27358483 TI - Two Affinity Sites of the Cannabinoid Subtype 2 Receptor Identified by a Novel Homogeneous Binding Assay. AB - Endocannabinoids act on G protein-coupled receptors that are considered potential targets for a variety of diseases. There are two different cannabinoid receptor types: ligands for cannabinoid type 2 receptors (CB2Rs) show more promise than those for cannabinoid type 1 receptors (CB1Rs) because they lack psychotropic actions. However, the complex pharmacology of these receptors, coupled with the lipophilic nature of ligands, is delaying the translational success of medications targeting the endocannabinoid system. We here report the discovery and synthesis of a fluorophore-conjugated CB2R-selective compound, CM-157 (3-[[4 [2-tert-butyl-1-(tetrahydropyran-4-ylmethyl)benzimidazol-5-yl]sulfonyl-2 pyridyl]oxy]propan-1-amine), which was useful for pharmacological characterization of CB2R by using a time-resolved fluorescence resonance energy transfer assay. This methodology does not require radiolabeled compounds and may be undertaken in homogeneous conditions and in living cells (i.e., without the need to isolate receptor-containing membranes). The affinity of the labeled compound was similar to that of the unlabeled molecule. Time-resolved fluorescence resonance energy transfer assays disclosed a previously unreported second affinity site and showed conformational changes in CB2R forming receptor heteromers with G protein-coupled receptor GPR55, a receptor for l-alpha lysophosphatidylinositol. The populations displaying subnanomolar and nanomolar affinities were undisclosed in competitive assays using a well known cannabinoid receptor ligand, AM630 (1-[2-(morpholin-4-yl)ethyl]-2-methyl-3-(4-methoxybenzoyl) 6-iodoindole), and TH-chrysenediol, not previously tested on binding to cannabinoid receptors. Variations in binding parameters upon formation of dimers with GPR55 may reflect decreases in binding sites or alterations of the quaternary structure of the macromolecular G protein-coupled receptor complexes. In summary, the homogeneous binding assay described here may serve to better characterize agonist binding to CB2R and to identify specific properties of CB2R on living cells. PMID- 27358484 TI - c-Myc Modulation and Acetylation Is a Key HDAC Inhibitor Target in Cancer. AB - Purpose: Histone deacetylase inhibitors (HDACi) are promising anticancer drugs. Although some HDACi have entered the clinic, the mechanism(s) underlying their tumor selectivity are poorly understood.Experimental Design and Results: Using gene expression analysis, we define a core set of six genes commonly regulated in acute myeloid leukemia (AML) blasts and cell lines. MYC, the most prominently modulated, is preferentially altered in leukemia. Upon HDACi treatment, c-Myc is acetylated at lysine 323 and its expression decreases, leading to TRAIL activation and apoptosis. c-Myc binds to the TRAIL promoter on the proximal GC box through SP1 or MIZ1, impairing TRAIL activation. HDACi exposure triggers TRAIL expression, altering c-Myc-TRAIL binding. These events do not occur in normal cells. Excitingly, this inverse correlation between TRAIL and c-Myc is supported by HDACi treatment ex vivo of AML blasts and primary human breast cancer cells. The predictive value of c-Myc to HDACi responsiveness is confirmed in vivo in AML patients undergoing HDACi-based clinical trials.Conclusions: Collectively, our findings identify a key role for c-Myc in TRAIL deregulation and as a biomarker of the anticancer action of HDACi in AML. The potential improved patient stratification could pave the way toward personalized therapies. Clin Cancer Res; 23(10); 2542-55. (c)2016 AACR. PMID- 27358486 TI - An Aggressive Subtype of Stage I Lung Adenocarcinoma with Molecular and Prognostic Characteristics Typical of Advanced Lung Cancers. AB - PURPOSE: The National Lung Cancer Screening Trial has confirmed that lung cancer mortality can be reduced if tumors are diagnosed early, that is, at stage I. However, a substantial fraction of stage I lung cancer patients still develop metastatic disease within 5 years from surgery. Prognostic biomarkers are therefore needed to identify patients at risk of an adverse outcome, who might benefit from multimodality treatment. EXPERIMENTAL DESIGN: We extensively validated a 10-gene prognostic signature in a cohort of 507 lung adenocarcinoma patients using formalin-fixed paraffin-embedded samples. Furthermore, we performed an integrated analysis of gene expression, methylation, somatic mutations, copy number variations, and proteomic profiles on an independent cohort of 468 patients from The Cancer Genome Atlas (TCGA). RESULTS: Stage I lung cancer patients (N = 351) identified as high-risk by the 10-gene signature displayed a 4-fold increased risk of death [HR = 3.98; 95% confidence interval (CI), 1.73-9.14], with a 3-year overall survival of 84.2% (95% CI, 78.7-89.7) compared with 95.6% (92.4-98.8) in low-risk patients. The analysis of TCGA cohort revealed that the 10-gene signature identifies a subgroup of stage I lung adenocarcinomas displaying distinct molecular characteristics and associated with aggressive behavior and poor outcome. CONCLUSIONS: We validated a 10-gene prognostic signature capable of identifying a molecular subtype of stage I lung adenocarcinoma with characteristics remarkably similar to those of advanced lung cancer. We propose that our signature might aid the identification of stage I patients who would benefit from multimodality treatment. Clin Cancer Res; 23(1); 62-72. (c)2016 AACR. PMID- 27358485 TI - HER3 Targeting Sensitizes HNSCC to Cetuximab by Reducing HER3 Activity and HER2/HER3 Dimerization: Evidence from Cell Line and Patient-Derived Xenograft Models. AB - PURPOSE: Our previous work suggested that HER3 inhibition sensitizes head and neck squamous cell carcinoma (HNSCC) to EGFR inhibition with cetuximab. This study aimed to define the role of HER3 in cetuximab resistance and the antitumor mechanisms of EGFR/HER3 dual targeting in HNSCC. EXPERIMENTAL DESIGN: We treated cetuximab-resistant HNSCC UMSCC1-C and parental UMSCC1-P cell lines with anti EGFR antibody cetuximab, anti-HER3 antibody MM-121, and their combination. We assessed activities of HER2, HER3, and downstream signaling pathways by Western blotting and cell growth by sulforhodamine B (SRB) and colony formation assays. HER3-specific shRNA was used to confirm the role of HER3 in cetuximab response. The combined efficacy and alterations in biomarkers were evaluated in UMSCC1-C xenograft and patient-derived xenograft (PDX) models. RESULTS: Cetuximab treatment induced HER3 activation and HER2/HER3 dimerization in HNSCC cell lines. Combined treatment with cetuximab and MM-121 blocked EGFR and HER3 activities and inhibited the PI3K/AKT and ERK signaling pathways and HNSCC cell growth more effectively than each antibody alone. HER3 knockdown reduced HER2 activation and resensitized cells to cetuximab. Cetuximab-resistant xenografts and PDX models revealed greater efficacy of dual EGFR and HER3 inhibition compared with single antibodies. In PDX tissue samples, cetuximab induced HER3 expression and MM-121 reduced AKT activity. CONCLUSIONS: Clinically relevant PDX models demonstrate that dual targeting of EGFR and HER3 is superior to EGFR targeting alone in HNSCC. Our study illustrates the upregulation of HER3 by cetuximab as one mechanism underlying resistance to EGFR inhibition in HNSCC, supporting further clinical investigations using multiple targeting strategies in patients who have failed cetuximab-based therapy. Clin Cancer Res; 23(3); 677-86. (c)2016 AACR. PMID- 27358487 TI - Combination Therapy with Anti-PD-1, Anti-TIM-3, and Focal Radiation Results in Regression of Murine Gliomas. AB - PURPOSE: Checkpoint molecules like programmed death-1 (PD-1) and T-cell immunoglobulin mucin-3 (TIM-3) are negative immune regulators that may be upregulated in the setting of glioblastoma multiforme. Combined PD-1 blockade and stereotactic radiosurgery (SRS) have been shown to improve antitumor immunity and produce long-term survivors in a murine glioma model. However, tumor-infiltrating lymphocytes (TIL) can express multiple checkpoints, and expression of >=2 checkpoints corresponds to a more exhausted T-cell phenotype. We investigate TIM 3 expression in a glioma model and the antitumor efficacy of TIM-3 blockade alone and in combination with anti-PD-1 and SRS. EXPERIMENTAL DESIGN: C57BL/6 mice were implanted with murine glioma cell line GL261-luc2 and randomized into 8 treatment arms: (i) control, (ii) SRS, (iii) anti-PD-1 antibody, (iv) anti-TIM-3 antibody, (v) anti-PD-1 + SRS, (vi) anti-TIM-3 + SRS, (vii) anti-PD-1 + anti-TIM-3, and (viii) anti-PD-1 + anti-TIM-3 + SRS. Survival and immune activation were assessed. RESULTS: Dual therapy with anti-TIM-3 antibody + SRS or anti-TIM-3 + anti-PD-1 improved survival compared with anti-TIM-3 antibody alone. Triple therapy resulted in 100% overall survival (P < 0.05), a significant improvement compared with other arms. Long-term survivors demonstrated increased immune cell infiltration and activity and immune memory. Finally, positive staining for TIM-3 was detected in 7 of 8 human GBM samples. CONCLUSIONS: This is the first preclinical investigation on the effects of dual PD-1 and TIM-3 blockade with radiation. We also demonstrate the presence of TIM-3 in human glioblastoma multiforme and provide preclinical evidence for a novel treatment combination that can potentially result in long-term glioma survival and constitutes a novel immunotherapeutic strategy for the treatment of glioblastoma multiforme. Clin Cancer Res; 23(1); 124-36. (c)2016 AACR. PMID- 27358488 TI - XPO1 Inhibition using Selinexor Synergizes with Chemotherapy in Acute Myeloid Leukemia by Targeting DNA Repair and Restoring Topoisomerase IIalpha to the Nucleus. AB - PURPOSE: Selinexor, a selective inhibitor of XPO1, is currently being tested as single agent in clinical trials in acute myeloid leukemia (AML). However, considering the molecular complexity of AML, it is unlikely that AML can be cured with monotherapy. Therefore, we asked whether adding already established effective drugs such as topoisomerase (Topo) II inhibitors to selinexor will enhance its anti-leukemic effects in AML. EXPERIMENTAL DESIGN: The efficacy of combinatorial drug treatment using Topo II inhibitors (idarubicin, daunorubicin, mitoxantrone, etoposide) and selinexor was evaluated in established cellular and animal models of AML. RESULTS: Concomitant treatment with selinexor and Topo II inhibitors resulted in therapeutic synergy in AML cell lines and patient samples. Using a xenograft MV4-11 AML mouse model, we show that treatment with selinexor and idarubicin significantly prolongs survival of leukemic mice compared with each single therapy. CONCLUSIONS: Aberrant nuclear export and cytoplasmic localization of Topo IIalpha has been identified as one of the mechanisms leading to drug resistance in cancer. Here, we show that in a subset of patients with AML that express cytoplasmic Topo IIalpha, selinexor treatment results in nuclear retention of Topo IIalpha protein, resulting in increased sensitivity to idarubicin. Selinexor treatment of AML cells resulted in a c-MYC-dependent reduction of DNA damage repair genes (Rad51 and Chk1) mRNA and protein expression and subsequent inhibition of homologous recombination repair and increased sensitivity to Topo II inhibitors. The preclinical data reported here support further clinical studies using selinexor and Topo II inhibitors in combination to treat AML. Clin Cancer Res; 22(24); 6142-52. (c)2016 AACR. PMID- 27358490 TI - Immunomodulatory Effect of Vitamin D after Allogeneic Stem Cell Transplantation: Results of a Prospective Multicenter Clinical Trial. AB - PURPOSE: We describe the results of a prospective multicenter phase I/II trial evaluating the impact of the use of vitamin D (VitD) from day -5 to +100 on the outcome of patients undergoing allogeneic transplantation (EudraCT: 2010-023279 25; ClinicalTrials.gov: NCT02600988). EXPERIMENTAL DESIGN: A total of 150 patients were included in three consecutive cohorts of 50 patients each group: control group (CG, not receive VitD); low-dose group (LdD, received 1,000 IU VitD daily); and high-dose group (HdD, 5,000 IU VitD daily). We measured levels of VitD, cytokines, and immune subpopulations after transplantation. RESULTS: No significant differences were observed in terms of cumulative incidence of overall and grades 2-4 acute GVHD in terms of relapse, nonrelapse mortality, and overall survival. However, a significantly lower cumulative incidence of both overall and moderate plus severe chronic GVHD (cGVHD) at 1 year was observed in LdD (37.5% and 19.5%, respectively) and HdD (42.4% and 27%, respectively) as compared with CG (67.5% and 44.7%, respectively; P < 0.05). In multivariable analysis, treatment with VitD significantly decreased the risk of both overall (for LdD: HR = 0.31, P = 0.002; for HdD: HR = 0.36, P = 0.006) and moderate plus severe cGVHD (for LdD: HR = 0.22, P = 0.001; for HdD: HR = 0.33, P = 0.01). VitD modified the immune response, decreasing the number of B cells and naive CD8 T cells, with a lower expression of CD40L. CONCLUSIONS: This is the first prospective trial that analyzes the effect of VitD postransplant. We observed a significantly lower incidence of cGVHD among patients receiving VitD. Interestingly, VitD modified the immune response after allo-SCT. Clin Cancer Res; 22(23); 5673-81. (c)2016 AACR. PMID- 27358489 TI - Epigenome-Wide Tumor DNA Methylation Profiling Identifies Novel Prognostic Biomarkers of Metastatic-Lethal Progression in Men Diagnosed with Clinically Localized Prostate Cancer. AB - PURPOSE: Aside from Gleason sum, few factors accurately identify the subset of prostate cancer patients at high risk for metastatic progression. We hypothesized that epigenetic alterations could distinguish prostate tumors with life threatening potential. EXPERIMENTAL DESIGN: Epigenome-wide DNA methylation profiling was performed in surgically resected primary tumor tissues from a population-based (n = 430) and a replication (n = 80) cohort of prostate cancer patients followed prospectively for at least 5 years. Metastasis was confirmed by positive bone scan, MRI, CT, or biopsy, and death certificates confirmed cause of death. AUC, partial AUC (pAUC, 95% specificity), and P value criteria were used to select differentially methylated CpG sites that robustly stratify patients with metastatic-lethal from nonrecurrent tumors, and which were complementary to Gleason sum. RESULTS: Forty-two CpG biomarkers stratified patients with metastatic-lethal versus nonrecurrent prostate cancer in the discovery cohort, and eight of these CpGs replicated in the validation cohort based on a significant (P < 0.05) AUC (range, 0.66-0.75) or pAUC (range, 0.007-0.009). The biomarkers that improved discrimination of patients with metastatic-lethal prostate cancer include CpGs in five genes (ALKBH5, ATP11A, FHAD1, KLHL8, and PI15) and three intergenic regions. In the validation dataset, the AUC for Gleason sum alone (0.82) significantly increased with the addition of four individual CpGs (range, 0.86-0.89; all P <0.05). CONCLUSIONS: Eight differentially methylated CpGs that distinguish patients with metastatic-lethal from nonrecurrent tumors were validated. These novel epigenetic biomarkers warrant further investigation as they may improve prognostic classification of patients with clinically localized prostate cancer and provide new insights on tumor aggressiveness. Clin Cancer Res; 23(1); 311-9. (c)2016 AACR. PMID- 27358491 TI - Xenotropic Murine Leukemia Virus-Related Virus (XMRV) and the Safety of the Blood Supply. AB - In 2006, a new virus, xenotropic murine leukemia virus-related virus (XMRV), was discovered in a cohort of U.S. men with prostate cancer. Soon after this initial finding, XMRV was also detected in samples from patients with chronic fatigue syndrome (CFS). The blood community, which is highly sensitive to the threat of emerging infectious diseases since the HIV/AIDS crisis, recommended indefinite deferral of all blood donors with a history of CFS. As XMRV research progressed, conflicting results emerged regarding the importance of this virus in the pathophysiology of prostate cancer and/or CFS. Molecular biologists traced the development of XMRV to a recombination event in a laboratory mouse that likely occurred circa 1993. The virus was propagated via cell lines derived from a tumor present in this mouse and spread through contamination of laboratory samples. Well-controlled experiments showed that detection of XMRV was due to contaminated samples and was not a marker of or a causal factor in prostate cancer or CFS. This paper traces the development of XMRV in the prostate and CFS scientific communities and explores the effect it had on the blood community. PMID- 27358492 TI - What Is the Link Between Hallucinations, Dreams, and Hypnagogic-Hypnopompic Experiences? AB - By definition, hallucinations occur only in the full waking state. Yet similarities to sleep-related experiences such as hypnagogic and hypnopompic hallucinations, dreams and parasomnias, have been noted since antiquity. These observations have prompted researchers to suggest a common aetiology for these phenomena based on the neurobiology of rapid eye movement (REM) sleep. With our recent understanding of hallucinations in different population groups and at the neurobiological, cognitive and interpersonal levels, it is now possible to draw comparisons between the 2 sets of experiences as never before. In the current article, we make detailed comparisons between sleep-related experiences and hallucinations in Parkinson's disease, schizophrenia and eye disease, at the levels of phenomenology (content, sensory modalities involved, perceptual attributes) and of brain function (brain activations, resting-state networks, neurotransmitter action). Findings show that sleep-related experiences share considerable overlap with hallucinations at the level of subjective descriptions and underlying brain mechanisms. Key differences remain however: (1) Sleep related perceptions are immersive and largely cut off from reality, whereas hallucinations are discrete and overlaid on veridical perceptions; and (2) Sleep related perceptions involve only a subset of neural networks implicated in hallucinations, reflecting perceptual signals processed in a functionally and cognitively closed-loop circuit. In summary, both phenomena are non-veridical perceptions that share some phenomenological and neural similarities, but insufficient evidence exists to fully support the notion that the majority of hallucinations depend on REM processes or REM intrusions into waking consciousness. PMID- 27358493 TI - TGF-beta Contributes to Impaired Exercise Response by Suppression of Mitochondrial Key Regulators in Skeletal Muscle. AB - A substantial number of people at risk of developing type 2 diabetes could not improve insulin sensitivity by physical training intervention. We studied the mechanisms of this impaired exercise response in 20 middle-aged individuals at high risk of developing type 2 diabetes who performed 8 weeks of controlled cycling and walking training at 80% individual Vo2 peak. Participants identified as nonresponders in insulin sensitivity (based on the Matsuda index) did not differ in preintervention parameters compared with high responders. The failure to increase insulin sensitivity after training correlates with impaired upregulation of mitochondrial fuel oxidation genes in skeletal muscle, and with the suppression of the upstream regulators PGC1alpha and AMPKalpha2. The muscle transcriptomes of the nonresponders are further characterized by the activation of transforming growth factor (TGF)-beta and TGF-beta target genes, which is associated with increases in inflammatory and macrophage markers. TGF-beta1 as inhibitor of mitochondrial regulators and insulin signaling is validated in human skeletal muscle cells. Activated TGF-beta1 signaling downregulates the abundance of PGC1alpha, AMPKalpha2, the mitochondrial transcription factor TFAM, and mitochondrial enzymes. Thus, the data suggest that increased TGF-beta activity in skeletal muscle can attenuate the improvement of mitochondrial fuel oxidation after training and contribute to the failure to increase insulin sensitivity. PMID- 27358494 TI - One Week of Bed Rest Leads to Substantial Muscle Atrophy and Induces Whole-Body Insulin Resistance in the Absence of Skeletal Muscle Lipid Accumulation. AB - Short (<10 days) periods of muscle disuse, often necessary for recovery from illness or injury, lead to various negative health consequences. The current study investigated mechanisms underlying disuse-induced insulin resistance, taking into account muscle atrophy. Ten healthy, young males (age: 23 +/- 1 years; BMI: 23.0 +/- 0.9 kg . m(-2)) were subjected to 1 week of strict bed rest. Prior to and after bed rest, lean body mass (dual-energy X-ray absorptiometry) and quadriceps cross-sectional area (CSA; computed tomography) were assessed, and peak oxygen uptake (VO2peak) and leg strength were determined. Whole-body insulin sensitivity was measured using a hyperinsulinemic-euglycemic clamp. Additionally, muscle biopsies were collected to assess muscle lipid (fraction) content and various markers of mitochondrial and vascular content. Bed rest resulted in 1.4 +/- 0.2 kg lean tissue loss and a 3.2 +/- 0.9% decline in quadriceps CSA (both P < 0.01). VO2peak and one-repetition maximum declined by 6.4 +/- 2.3 (P < 0.05) and 6.9 +/- 1.4% (P < 0.01), respectively. Bed rest induced a 29 +/- 5% decrease in whole-body insulin sensitivity (P < 0.01). This was accompanied by a decline in muscle oxidative capacity, without alterations in skeletal muscle lipid content or saturation level, markers of oxidative stress, or capillary density. In conclusion, 1 week of bed rest substantially reduces skeletal muscle mass and lowers whole-body insulin sensitivity, without affecting mechanisms implicated in high-fat diet-induced insulin resistance. PMID- 27358495 TI - Zooming in on selectins in cancer. AB - Selectins are involved in leukocyte and cancer cell trafficking, which can be targeted with drugs and nanoparticles (Shamay et al., this issue). PMID- 27358496 TI - Multicriteria decision analysis and core values for enhancing vaccine-related decision-making. AB - Vaccines have the potential to transform the health of all individuals and to reduce the health inequality between rich and poor countries. However, to achieve these goals, it is no longer sufficient to prioritize vaccine development using cost-effectiveness as the sole indicator. During a symposium entitled "Mission Grand Convergence-The Role of Vaccines," held in Siena, Italy, in July 2015, key stakeholders agreed that the prioritization of vaccine development and deployment must use multicriteria decision-making based on the following core concepts: (i) mortality and severity of the disease, (ii) vaccine safety considerations, and (iii) economic evaluation that captures the full benefits of vaccination. PMID- 27358498 TI - Low alpha-defensin gene copy number increases the risk for IgA nephropathy and renal dysfunction. AB - Although a major source of genetic variation, copy number variations (CNVs) and their involvement in disease development have not been well studied. Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. We performed association analysis of the DEFA1A3 CNV locus in two independent IgAN cohorts of southern Chinese Han (total of 1189 cases and 1187 controls). We discovered three independent copy number associations within the locus: DEFA1A3 [P = 3.99 * 10(-9); odds ratio (OR), 0.88], DEFA3 (P = 6.55 * 10( 5); OR, 0.82), and a noncoding deletion variant (211bp) (P = 3.50 * 10(-16); OR, 0.75) (OR per copy, fixed-effects meta-analysis). While showing strong association with an increased risk for IgAN (P = 9.56 * 10(-20)), low total copy numbers of the three variants also showed significant association with renal dysfunction in patients with IgAN (P = 0.03; hazards ratio, 3.69; after controlling for the effects of known prognostic factors) and also with increased serum IgA1 (P = 0.02) and galactose-deficient IgA1 (P = 0.03). For replication, we confirmed the associations of DEFA1A3 (P = 4.42 * 10(-4); OR, 0.82) and DEFA3 copy numbers (P = 4.30 * 10(-3); OR, 0.74) with IgAN in a Caucasian cohort (531 cases and 198 controls) and found the 211bp variant to be much rarer in Caucasians. We also observed an association of the 211bp copy number with membranous nephropathy (P = 1.11 * 10(-7); OR, 0.74; in 493 Chinese cases and 500 matched controls), but not with diabetic kidney disease (in 806 Chinese cases and 786 matched controls). By explaining 4.96% of disease risk and influencing renal dysfunction in patients with IgAN, the DEFA1A3 CNV locus may be a potential therapeutic target for developing treatments for this disease. PMID- 27358497 TI - P-selectin is a nanotherapeutic delivery target in the tumor microenvironment. AB - Disseminated tumors are poorly accessible to nanoscale drug delivery systems because of the vascular barrier, which attenuates extravasation at the tumor site. We investigated P-selectin, a molecule expressed on activated vasculature that facilitates metastasis by arresting tumor cells at the endothelium, for its potential to target metastases by arresting nanomedicines at the tumor endothelium. We found that P-selectin is expressed on cancer cells in many human tumors. To develop a targeted drug delivery platform, we used a fucosylated polysaccharide with nanomolar affinity to P-selectin. The nanoparticles targeted the tumor microenvironment to localize chemotherapeutics and a targeted MEK (mitogen-activated protein kinase kinase) inhibitor at tumor sites in both primary and metastatic models, resulting in superior antitumor efficacy. In tumors devoid of P-selectin, we found that ionizing radiation guided the nanoparticles to the disease site by inducing P-selectin expression. Radiation concomitantly produced an abscopal-like phenomenon wherein P-selectin appeared in unirradiated tumor vasculature, suggesting a potential strategy to target disparate drug classes to almost any tumor. PMID- 27358500 TI - Salinity as a barrier for ship hull-related dispersal and invasiveness of dreissenid and mytilid bivalves. AB - The benthic stages of Dreissenidae and Mytilidae may be dispersed over long distances while attached to ship hulls. Alternatively, larvae may be transported by water currents and in the ballast and bilge water of ships and vessels. To gain insight into dispersal potential and habitat suitability, survival of the benthic stages of two invasive dreissenid species (Dreissena polymorpha and Mytilopsis leucophaeata) and one mytilid species (Mytilus edulis) chosen based on their occurrence in fresh, brackish and sea water, respectively, were tested in relation to salinity. They were exposed to various salinities in mesocosms during three long-term experiments at outdoor temperatures. Mussel survival was studied without prior acclimation, reflecting conditions experienced when attached to ship hulls while travelling along a salinity gradient from fresh or brackish water to sea water, or vice versa. Initially, mussels react to salinity shock by temporarily closing their valves, suspending ventilation and feeding. However, this cannot be maintained for long periods and adaptation to higher salinity must eventually occur. Bivalve survival was monitored till the last specimen of a test cohort died. The results of the experiments allowed us to distinguish favorable (f.: high tolerance) and unfavorable (u.: no or low tolerance) salinity ranges in practical salinity units (PSU) for each species, viz. for D. polymorpha 0.2-6.0 PSU (f.), 7.0-30.0 PSU (u.), for M. leucophaeata 0.2-17.5 PSU (f.), 20.0-30.0 PSU (u.) and for M. edulis 10.5-36.0 PSU (f.), 0.2-9.0 and 40 PSU (u.). At the unfavorable salinities, all mussels died within 14 days of initial exposure with the exception of M. edulis (23-30 days). The maximum duration of survival of single specimens of D. polymorpha was 318 days at a salinity of 3.2 PSU, of M. leucophaeata 781 days at 15.0 PSU and of M. edulis 1052 days at 15.0 PSU. The number of days survived was compared with the duration of actual ship voyages to estimate the real world survival potentials of species dependent of salinity changes, travel distances and durations. The conclusion is that salinity shocks during the trip were survived within the favorable salinity range but that the species tolerate only for a few weeks the unfavorable salinity range. This functions as a barrier for dispersal. However, at faster and more frequent shipping in the future salinity can become no longer very important as a dispersal barrier. PMID- 27358499 TI - Tumor-derived circulating endothelial cell clusters in colorectal cancer. AB - Clusters of tumor cells are often observed in the blood of cancer patients. These structures have been described as malignant entities for more than 50 years, although their comprehensive characterization is lacking. Contrary to current consensus, we demonstrate that a discrete population of circulating cell clusters isolated from the blood of colorectal cancer patients are not cancerous but consist of tumor-derived endothelial cells. These clusters express both epithelial and mesenchymal markers, consistent with previous reports on circulating tumor cell (CTC) phenotyping. However, unlike CTCs, they do not mirror the genetic variations of matched tumors. Transcriptomic analysis of single clusters revealed that these structures exhibit an endothelial phenotype and can be traced back to the tumor endothelium. Further results show that tumor derived endothelial clusters do not form by coagulation or by outgrowth of single circulating endothelial cells, supporting a direct release of clusters from the tumor vasculature. The isolation and enumeration of these benign clusters distinguished healthy volunteers from treatment-naive as well as pathological early-stage (<=IIA) colorectal cancer patients with high accuracy, suggesting that tumor-derived circulating endothelial cell clusters could be used as a means of noninvasive screening for colorectal cancer. In contrast to CTCs, tumor derived endothelial cell clusters may also provide important information about the underlying tumor vasculature at the time of diagnosis, during treatment, and throughout the course of the disease. PMID- 27358501 TI - A chromium tricarbonyl complex featuring the 4,6 bis(diphenylphosphinomethyl)dibenzothiophene (PSPPh) ligand. AB - ABSTRACT: The new PSP pincer ligand 4,6 bis(diphenylphosphinomethyl)dibenzothiophene (PSPPh) was prepared in 89 % yield. With this ligand, a solvothermal synthesis of a Cr complex of the type [Cr(kappa3P,S,P-PSP)(CO)3] is described. The X-ray structure of this compound is presented. We demonstrate that the solvothermal synthesis technique provides a powerful, simple, and practical synthetic method resulting in a high isolated yield in a short reaction time. GRAPHICAL ABSTRACT: PMID- 27358502 TI - First example of stepwise, zwitterionic mechanism for bicyclo[2.2.1]hept-5-ene (norbornene) formation process catalyzed by the 1-butyl-3-methylimidazolium cations. AB - ABSTRACT: B3LYP/6-31++G(d) calculations indicated that the reaction of (2E)-3 phenyl-2-nitroprop-2-enenitrile with cyclopentadiene catalyzed by cations of 1,3 dialkylimidazolium ionic liquid shall not take place according to the classical scheme of one-step [2+4] Diels-Alder cycloaddition. Along the path finally leading to bicyclo[2.2.1]hept-5-ene (norbornene) with a nitro group in endo orientation, the process of bicarbocyclic skeleton formation shall take place according to the domino mechanism, via [2+4] heterocycloadduct. On the other hand, along the path leading finally to bicyclo[2.2.1]hept-5-ene with a nitro group in exo orientation, acyclic adduct with a zwitterionic nature is formed in the first reaction, which undergoes cyclisation next in the second step of the reaction. GRAPHICAL ABSTRACT: PMID- 27358503 TI - Determination the Usefulness of AhHMA4p1::AhHMA4 Expression in Biofortification Strategies. AB - AhHMA4 from Arabidopsis thaliana encodes Zn/Cd export protein that controls Zn/Cd translocation to shoots. The focus of this manuscript is the evaluation of AhHMA4 expression in tomato for mineral biofortification (more Zn and less Cd in shoots and fruits). Hydroponic and soil-based experiments were performed. Transgenic and wild-type plants were grown on two dilution levels of Knop's medium (1/10, 1/2) with or without Cd, to determine if mineral composition affects the pattern of root/shoot partitioning of both metals due to AhHMA4 expression. Facilitation of Zn translocation to shoots of 19-day-old transgenic tomato was noted only when plants were grown in the more diluted medium. Moreover, the expression pattern of Zn-Cd-Fe cross-homeostasis genes (LeIRT1, LeChln, LeNRAMP1) was changed in transgenics in a medium composition-dependent fashion. In plants grown in soil (with/without Cd) up to maturity, expression of AhHMA4 resulted in more efficient translocation of Zn to shoots and restriction of Cd. These results indicate the usefulness of AhHMA4 expression to improve the growth of tomato on low-Zn soil, also contaminated with Cd. PMID- 27358504 TI - Bacillus thuringiensis B1(2015b) is a Gram-Positive Bacteria Able to Degrade Naproxen and Ibuprofen. AB - A Gram-positive bacterium, designated as strain B1(2015b), was isolated from the soil of the chemical factory "Organika-Azot" in Jaworzno, Poland. On the basis of 16S rRNA gene sequence analysis, the isolated strain was classified as a Bacillus thuringiensis species. Strain B1(2015b) is able to degrade ibuprofen and naproxen, however, these compounds are not sufficient carbon sources for this strain. In the presence of glucose, Bacillus thuringiensis B1(2015b) degrades ibuprofen and naproxen with higher efficiency. Twenty milligrams per liter of ibuprofen was degraded within 6 days and 6 mg l-1 of naproxen was removed within 35 days. Simultaneously, the growth of the bacterial culture was observed. The obtained results suggest that Bacillus thuringiensis B1(2015b) appears to be a powerful and useful tool in the bioremediation of non-steroidal anti-inflammatory drugs-contaminated environment. PMID- 27358505 TI - A teleofunctional account of evolutionary mismatch. AB - When the environment in which an organism lives deviates in some essential way from that to which it is adapted, this is described as "evolutionary mismatch," or "evolutionary novelty." The notion of mismatch plays an important role, explicitly or implicitly, in evolution-informed cognitive psychology, clinical psychology, and medicine. The evolutionary novelty of our contemporary environment is thought to have significant implications for our health and well being. However, scientists have generally been working without a clear definition of mismatch. This paper defines mismatch as deviations in the environment that render biological traits unable, or impaired in their ability, to produce their selected effects (i.e., to perform their proper functions in Neander's sense). The machinery developed by Millikan in connection with her account of proper function, and with her related teleosemantic account of representation, is used to identify four major types, and several subtypes, of evolutionary mismatch. While the taxonomy offered here does not in itself resolve any scientific debates, the hope is that it can be used to better formulate empirical hypotheses concerning the effects of mismatch. To illustrate, it is used to show that the controversial hypothesis that general intelligence evolved as an adaptation to handle evolutionary novelty can, contra some critics, be formulated in a conceptually coherent way. PMID- 27358506 TI - Expression of Growth Hormone Genes in Transgenic Mice. AB - Human or rat growth hormone (GH) genes have been introduced into all cells of a mouse by microinjection of fertilized eggs but they were not expressed under their own promoters. However, substitution of a mouse metallothionein (MT) promoter allowed expression and regulation comparable to that of the endogenous MT genes. These fusion genes have been used to stimulate the growth of both normal mice and dwarf mice that lack sufficient GH. Substitution of a rat elastase-I promoter directed expression of GH exclusively to the acinar cells of the pancreas. Progress has been made towards developing the hGH gene into a vector that is not expressed in vivo unless an enhancer element is inserted. Recombination between overlapping DNA fragments derived from a MThGH gene, each of which is nonfunctional, has been observed when they are coinjected into mouse eggs. In some cases, functional hGH was produced as evidenced by enhanced growth of the mice. PMID- 27358508 TI - Cashless, Tech-Savvy Future Surgeon. PMID- 27358509 TI - Reduced Port Thoracoscopic Surgery for Mediastinal and Pleural Disease: Experiences in a Single Institution. AB - The purpose of this study was to present our current experience with reduced port thoracoscopic surgery (RPTS) for the treatment of mediastinal and pleural disease and thereafter discuss its indications and technical challenges. A total of 11 patients underwent surgery by the RPTS approach for the following conditions: thymoma (n = 2), bronchogenic cyst (n = 2), metastatic pleural tumor, thymic cyst, solitary fibrous tumor, pulmonary sequestration, pericardial cyst, neurinoma, and malignant lymphoma (n = 1). An Endo Relief forceps (Hope Denshi Co, Ltd, Chiba, Japan) was used for three of the surgical procedures. The elements of the data set consisted of gender, age, duration of operation, drain placement, hospital stay, mass location, and mass size. The median surgical time was 45 min (range, 40-78 min). There were no intraoperative complications and no need for a second surgery to open additional ports. The duration until chest tube removal was 1 day for all the cases. The median hospital stay was 4 days (range, 3-6 days). The median mass size was 2.2 cm (range, 1.2-4.2 cm). The median length of skin incision was 2.0 cm (range, 2.0-3.5 cm). In conclusion, RPTS for mediastinal and pleural disease may be a possible alternative approach to conventional multiportal video-assisted thoracoscopic surgery (VATS). Although it is technically plausible and feasible for selected cases, the issues of patient acceptability and cosmetic and oncological results remain to be determined in the future with randomized-controlled trials and long-term follow-up. PMID- 27358507 TI - Microscopy techniques for investigating the control of organic constituents on biomineralization. AB - This article addresses recent advances in the application of microscopy techniques to characterize crystallization processes as they relate to biomineralization and bio-inspired materials synthesis. In particular, we focus on studies aimed at revealing the role organic macromolecules and functionalized surfaces play in modulating the mechanisms of nucleation and growth. In nucleation studies, we explore the use of methods such as in situ transmission electron microscopy, atomic force microscopy, and cryogenic electron microscopy to delineate formation pathways, phase stabilization, and the competing effects of free energy and kinetic barriers. In growth studies, emphasis is placed on understanding the interactions of macromolecular constituents with growing crystals and characterization of the internal structures of the resulting composite crystals using techniques such as electron tomography, atom probe tomography, and vibrational spectromicroscopy. Examples are drawn from both biological and bio-inspired synthetic systems. PMID- 27358510 TI - A Study on Role of Laparoscopic Sleeve Gastrectomy in the Management of Morbid Obesity. AB - Obesity has assumed a pandemic and is responsible for serious medical, social, psychological, and economic implications, affecting all ages and socioeconomic groups. Hence, this prospective study was carried out to study the surgical benefits in such patients. A Prospective interventional study was carried out from June 2010 to November 2012 at IGGMC Nagpur performing laparoscopic sleeve gastrectomy (LSG) in morbidly obese patients, and its efficacy was determined. A total of 56 patients were studied. 26 (46.42 %) being males and 30 (53.57 %) females. The maximum number of patient's, i.e., 32 (57.14 %) were in the range of BMI 40-44.99 kg/m(2) with mean BMI-43.25 kg/m(2). Mean weight was 117 kg (range 92-180 kg). Common comorbidities observed were hypertension in 43 (76.78 %), bronchial asthma in 31 (55.35 %), and diabetes in 21 (37.5 %). All patients treated with LSG had a mean operative time of 154.9 min (range 110-310 min) with 0 % leak, one conversion to open, and no mortality. Postoperative hospital stay was 3.54 days (range 3-7). Complications were minimal with prolonged vomiting seen significantly in 28 (50 %) patients. Follow up at 24 months showed mean weight 74.72 kg (68-81 kg) with mean excess weight loss of 67.71 % (62.79-71.05 %) causing a mean BMI of 28.42 kg/m(2) (26.56-30.44 kg/m(2)). It also reduced mean BP to 120.36 mmHg (110-144 mmHg) and mean fasting blood sugar to 100.63 mg/dl (80-146 mg/dl). Surgery for obesity is definitely an answer for this gift of modernization, and LSG is a safe and effective technique for achieving weight loss. Quality of life improves astonishingly and adds confidence to this mentally traumatic entity called "OBESITY". PMID- 27358511 TI - The Reversal of Stoma Following Open Abdomen Management. AB - Bowel stoma formation is very often required during open abdomen (OA) management; we aim to report our stoma reversal series following OA management retrospectively. A retrospective analysis of 31 patients who underwent the reversal of the stoma created during OA management between January 2008 and September 2014 was performed. Twenty-eight of these 31 patients were included in this study. The stoma-related complications are more common after OA management during waiting time interval for reversal. At this time interval, patients with jejunostomy had more stoma-related complications than patients with ileostomy (p = 0.008) and colostomy. (p = 0.001). Waiting time interval was shorter for reversal of jejunostomy than reversal of ileostomy (p = 0.014) and colostomy (p = 0.001). Operation time for jejunostomy (p = 0.016) and colostomy reversal (p = 0.001) were significantly longer than the ileostomy reversal. There was no difference between early and late reversal of stoma regarding morbidity and mortality. The stoma-related complications are more common following OA management during waiting time interval for stoma reversal. The reversal time is more critical for this kind of patients especially with life-threatening complicated jejunostomy. For loop stoma created during OA management, the reversal may be performed after average 50 days without increasing morbidity and mortality. The reversal of end stoma created during OA management has high morbidity. If it is possible, loop stoma should be preferred during OA management. PMID- 27358512 TI - Peripheral Arterial Injuries: an Indian Experience. AB - Arterial injuries present the most challenging conditions in surgical practice. Many fail to reach the specialist in time and end up losing limbs or lives. Though well addressed elsewhere, it has received less attention in developing countries like India. There is a need to study these injuries from the perspective of countries like India. The aims of the study are to (1) analyze the epidemiology, presentation, and outcomes of arterial injuries operated by the author in Indian settings; (2) identify factors associated with adverse outcomes; and (3) discuss the critical issues with relevance to our country. Retrospective analysis of arterial injuries operated by the author between July 2010 and February 2014 at our institution was performed. Patients with feasibility of revascularization were included and nonviable limbs requiring primary amputations were excluded. Sixty-one patients fulfilled the criteria of which 55 (90.1 %) were males and 6 (9.8 %) females aged between 5 and 70 years. The mean duration of presentation was 21 h. Majority were resultant of road traffic accidents (62.7 %). Among 49 (80.3 %) noniatrogenic injuries, the mechanism was blunt in 46 (93.8 %, n = 49) and penetrating in 3 (6.1 %) cases. Iatrogenic injuries were seen in 12 (19.6 %) cases. Lower limbs accounted for 37 (60.6 %) cases, popliteal segment being common, 22 (36 %) cases. Bony injuries were associated in 39 (63.9 %) cases. The most common procedure was interposition graft (49.1 %). Six (9.8 %) patients required an amputation resulting in 55 (90.1 %) salvaged limbs. Reaching a specialist center in appropriate time can result in good limb salvage rates and functional outcomes. Creating awareness and training the personnel are the critical issues in the management of arterial injuries in India. PMID- 27358513 TI - Prognostic Factors of Postoperative Morbidity and Mortality of Adult Strangulated Groin Hernia. AB - The aim of this work is provide the results of the surgical treatment of strangulated groin hernias and determine morbidity and mortality risk factors. It is a retrospective study related to the 288 records of patients aged 15 years and more, who underwent emergency surgery for strangulated groin hernia from January 2007 to December 2012. Postoperative evolution was assessed on the morbidity, mortality, and length of hospital stay. Mortality and morbidity risk factors were studied. The statistical analysis was conducted with the chi-square test and Fischer's exact test with a significance level of 5 %. Strangulated groin hernias account for 42.2 % of the overall groin hernia operations conducted during the study period (288/697). Necroses were present in 59 (20.5 %) patients. The mortality rate was 6.2 % (n = 18). Admission time superior or equal to 48 h (p = 0.002), American Society of Anesthesiologists (ASA) class superior or equal to III (p = 0.002), presence of preoperative strangulated groin hernia complication (peritonitis, occlusion, hernia abscesses) (p = 0.001), bowel necrosis (p = 0.000), and bowel resection (p = 0.000) were statistically related to a high risk of death. Forty-two (n = 42) postoperative complications were recorded in 34 (11.8 %) patients. These complications were outnumbered by postoperative parietal suppuration (n = 26) which led to three cases of evisceration. Bowel necrosis was related to a high risk of postoperative complications (p = 0.002). Reoperation was necessary for 13 patients. The length of stay in hospital was 4 days (range between 1 and 28 days). The average follow-up period was 7 months. No recurrence was noticed during this period. Delay in consultation, high ASA class, and moreover, bowel necrosis requiring bowel resection are the factors of unfavorable postoperative results. Groin hernias are an avoidable death cause provided that early treatment of strangulated hernias and the elective treatment of non complicated hernias are conducted. PMID- 27358514 TI - Learning Curve in Laparoscopic Inguinal Hernia Repair: Experience at a Tertiary Care Centre. AB - One of the major reasons for laparoscopy not having gained popularity for repair of groin hernia is the perceived steep learning curve. This study was conducted to assess the learning curve and to predict the number of cases required for a surgeon to become proficient in laparoscopic groin hernia repair, by comparing two laparoscopic surgeons. The learning curve evaluation parameters included operative time, conversions, intraoperative complications and postoperative complications, and these were compared between the senior and the junior surgeon. One hundred thirty-eight cases were performed by the senior surgeon, and 63 cases by the junior surgeon. Both were comparable in terms of intraoperative and postoperative complications. Using the moving average method, minimum of 13 laparoscopic hernia repairs are required to reach at par the operating time of an experienced surgeon. For total extraperitoneal (TEP) repair, the number of cases was 14; and for transabdominal preperitoneal (TAPP) repair, this number was 13. PMID- 27358515 TI - Epidermal Sutureless Closure of the Umbilical Base Following Laparoscopic Colectomy for Colon Cancer. AB - At our institute, a non-suturing method for closure of the umbilical epidermis has been used in laparoscopic colorectal resection to prevent umbilical wound infection. We performed a retrospective evaluation of the incidence of umbilical wound infection using this technique for patients with colorectal cancer. From 2010 to 2014, 178 consecutive patients underwent elective laparoscopic resection of colorectal cancer. The umbilical fascia was closed using interrupted multifilament absorbable sutures. The skin surface of the umbilicus was compressed using a cotton ball and sealed by water vapor-permeable film. Three (1.7 %) patients required conversion from laparoscopic to open surgery. The mean surgery time was 174 +/- 48 min, intraoperative blood loss was 29 +/- 75 mL, and postoperative hospital stay was 10.5 +/- 6.7 days. According to the Centers for Disease Control and Prevention criteria, umbilical superficial wound infection occurred in two (1.1 %) patients. The two patients recovered from their wound infections after a few days of drainage, and their hospital discharge was not delayed. Deep umbilical wound infection did not occur in any patient. Our non suturing closure technique appeared to be effective in preventing wound infection after laparoscopic resection of colon cancer. PMID- 27358516 TI - Review of Pancreaticoduodenal Trauma with a Case Report. AB - Complex anatomical relation of the duodenum, pancreas, biliary tract, and major vessels plays to obscure pancreaticoduodenal injuries. Causes of pancreaticoduodenal injuries are blunt trauma (traffic accidents, sport injuries) in 25 % of cases and penetrating abdominal injuries (stab wounds and firearm injuries) in 75 % of cases. Duodenal injuries are reported to occur in 0.5 to 5 % of all abdominal trauma cases and are observed in 11 % of abdominal firearm wounds, 1.6 % of abdominal stab wounds, and 6 % of blunt trauma. Retroperitoneal and deep abdominal localization of duodenum as an organ contribute to the difficulty in diagnosis and treatment. There are three important major points regarding treatment of duodenal injuries: (1) operation timing and decision, (2) Intraoperative detection, and (3) post-operative care. Therefore, it is difficult to diagnose and treat duodenal trauma. We would like to present a 21-year-old male patient with pancreaticoduodenal injury who presented to our emergency service after firearm injury to his abdomen and discuss his treatment with a short review of related literature. PMID- 27358517 TI - A Review of the Long-Term Oncologic Outcomes of Robotic Surgery Versus Laparoscopic Surgery for Colorectal Cancer. AB - The goal of this review was to compare long-term oncologic outcomes of robotic versus laparoscopic resection of colorectal cancer. A literature search was performed using PubMed, EMBASE, Cochrane, and Medline (2002-2014). Search terms: laparoscopic, robotic, rectal, colon, surgery, oncologic, and outcomes. Studies comparing overall and disease free survival of robotic versus laparoscopic surgery for colorectal cancer were included. Meta-analysis was performed using OpenMeta[Analyst] for Windows 8. Five studies were identified reporting on overall survival, disease free survival, lymph node extraction, and distal and circumferential resection margin. Three hundred and seventeen patients underwent robotic resection and 368 underwent laparoscopic resection, with similar demographics. Operative times were longer with robotic resections, with no difference in estimated blood loss (EBL) or length of stay. The disease stage was distributed similarly in both groups. Similar numbers underwent neo-adjuvant therapy. Laparoscopic resection was associated with 3.2 mm larger distal resection margins (p = 0.04) and 2.2 more lymph nodes removed (p = 0.001), but with equivalent circumferential resection margin status. Disease-free and overall survival was equivalent. Robotic and laparoscopic surgery for colorectal cancer offer comparable overall and disease free survival. Laparoscopic surgery offered a slight advantage in operative time, distal margin, and lymph node yield. Larger, prospective trials are needed to confirm the equivalence of these approaches. PMID- 27358518 TI - Percutaneous Catheter Drainage in Infected Pancreatitis Necrosis: a Systematic Review. AB - The primary aim of this study was to present the outcomes of percutaneous catheter drainage (PCD) in patients with infected pancreatitis necrosis. A second aim was to focus on disease severity, catheter size, and additional surgical intervention. A literature search of the PubMed/MEDLINE/Cochrane Library (January 1998 to February 2015) databases was conducted. All randomized, non-randomized, and retrospective studies with data on PCD techniques and outcomes in patients with infected pancreatitis necrosis were included. Studies that reported data on PCD along with other interventions without the possibility to discriminate results specific to PCD were excluded. The main outcomes were mortality, major complications, and definitive successful treatment with percutaneous catheter drainage alone. Fifteen studies of 577 patients were included. There was only one randomized, controlled trial, and most others were retrospective case series. Organ failure before PCD occurred in 55.3 % of patients. With PCD alone, definitive successful treatment was 56.2 % of patients. Additional surgical intervention was required after PCD in 38.5 % of patients. The overall mortality rate was 18 % (104 of 577 patients). Complications occurred in 25.1 % of patients, and fistula was the most common complication. PCD is an efficient tool for treatment in the majority of patients with infected pancreatitis necrosis as the only intervention. Multiple organ failures before PCD are negative parameters for the outcome of the disease. Large catheters fail to prove to be more effective for draining necrotic tissue. However, in the extent of multi-morbid patients, to determine one single prognostic factor seems to be difficult. PMID- 27358519 TI - Urothelial Carcinoma in Pediatric Patient. AB - Transitional cell carcinoma as a cause of hematuria is a rare entity in the pediatric age group. An 11-year-old child presented with gross, painless hematuria. Ultrasonogram and computed tomography scan of the child revealed a tumor in the posterolateral wall of the bladder. Cystoscopically, the mass was present in the bladder away from the trigone area about 2 cm lateral to the right ureteric orifice. Transurethrally, the tumor was excised by a cystoscope. Histopathologically, it was a low-grade noninvasive urothelial carcinoma of the bladder. A follow-up cystoscopy at 6 months and 1 year had no recurrence. Literature review revealed the pediatric age group as an uncommon age for urothelial carcinoma of bladder, which has a different biological behavior of being low malignant potential compared to their adult counterpart. They have been treated with transurethral resection of bladder tumor without any adjuvant therapy. There is no definite follow-up schedule for these tumors as it occurs in very small number of cases. PMID- 27358520 TI - Retropancreatic Ovarian Tumor. AB - Retroperitoneal mucinous cystadenomas are rare lesions (less than 50 reported) characterized by presence of ovary like stroma of unknown origin. However, germinal component of ovary has never been found in them. The pancreas occasionally gives rise to mucinous cystadenomas, but they are always intrapancreatic. We report a unique case of a rare retroperitoneal mucinous cystadenomas with presence of ovarian follicles in a 45-year-old lady who presented with an abdominal mass. This was successfully excised. Though retroperitoneal mucinous cystadenomas are rare, presence of ovarian follicle (germ cell) in them has never been reported before. PMID- 27358521 TI - Hydrocele of Femoral Hernial Sac-an Extremely Rare Case. AB - A previously healthy 40-year-old woman presented with a right groin swelling for the last 2 years. Diagnosed preoperatively as uncomplicated, irreducible epiplocele of right femoral hernia, later per-operatively was diagnosed as hydrocele of femoral hernial sac also known as "femorocele"; ultrasound abdomen and groin demonstrated as a cystic mass right groin with no precise origin. All other basic line investigations within normal limits, except anemia 7 gm %, corrected to 10 gm %, by preoperative transfusions of 2 units of complete fresh blood. After low approach incision, excision of hydrocele sac, and feormal hernia repair were done with approximation of iliopectineal ligament to inguinal ligament, patient was discharged on 5th postoperative day with satisfactory wound healing and uneventful hospitalization. PMID- 27358522 TI - Congenital Right Morgagni Hernia Presenting in an Adult-a Case Report. AB - Patients with congenital diaphragmatic hernias (CDH) usually present in the neonatal period with respiratory distress. Delayed presentation of CDH in adults is rare and difficult to diagnose. We present a 42-year-old female patient who came with complaints of epigastric pain and breathlessness on exertion. X-ray and CT scan of the chest revealed a right-sided Morgagni hernia. The contents of the hernia were reduced and a primary tension free repair of the hernia defect was done through laparotomy. The postoperative course was uneventful. A strong clinical suspicion and good interpretation of radiological images help diagnose CDH which present late. Prompt surgical repair is mandatory and the outcomes are usually favorable. Primary repair is usually successful; however, mesh repair may be required for larger defects. PMID- 27358523 TI - Common Bile Duct Obstruction Due to Surgical Clips Following Laparoscopic Cholecystectomy Treated with Percutaneous Balloon Dilatation. AB - Bile duct injury is a commonly seen complication of the laparoscopic cholecystectomy (LC) approach, which can even lead to a life-threatening condition and endoscopic retrograde cholangiopancreatography (ERCP) is the first line choice in treatment. Beside this, it can be concluded that percutaneous transhepatic cholangiography (PTC) and balloon dilatation methods may also constitute a reasonable selection with non-invasive, feasible and effective aspects prior to open surgery. In the present case, we report the management of a bile duct obstruction due to surgical clips following LC, treated with PTC and balloon dilatation instead of surgical procedure in a child patient. PMID- 27358524 TI - Abdominal Cocoon: "Cauliflower Sign" on CT Scan. AB - A case of an abdominal cocoon that showed a characteristic "cauliflower sign" on CT scan has been presented. PMID- 27358525 TI - New Breast Pain Chart for Objective Record of Mastalgia. AB - Mastalgia is the commonest affliction of mammary gland among ladies of the reproductive age group. Since etiopathogenesis and therapy are different for cyclical and noncyclical pain, it is imperative to ascertain the exact type correctly. This is usually done in the breast clinics by advising the patient to fill a pain diary over a period of 2 months over two menstrual cycles. The Cardiff pain chart records the severity of pain in the form of a triangle for mild to moderate pain and a square for severe pain. Moreover, Cardiff pain chart does not allow a patient to record the severity of pain on days of menses, as she has to put the letter "P" in the box. These problems have been resolved in the new breast pain chart. In the new pain chart, the lady records pain severity in the form of visual linear analogue scale score on every day of menstrual cycle. She enters her menstrual experience on a separate part of chart, which allows us to visualize the full month's pain severity in an uncluttered way. PMID- 27358526 TI - Totally Laparoscopic Total Gastrectomy for Gastric Cancer at a Single Institutional Experience and Changes in Technique of Esophagojejunostomy. AB - The totally laparoscopic total gastrectomy (TLTG) for gastric cancer has not gained widespread acceptance due to its technical difficulties, especially with the intracorporeal esophagojejunostomy (IEJS). Various modified procedures for the IEJS have been devised, but an optimal method has not yet been standardized. A total of 32 consecutive patients (23 men and 9 women) underwent TLTGs for gastric cancer, between December of 2009 and December of 2014 at the Iwate Medical University Hospital, and were enrolled in this study. Here, we report our institution's experience with TLTGs, with changes in the IEJS. The study participants had a mean age of 66.8 years and a body mass index of 22.8 kg/m2. The mean operation time and blood loss were 356.1 min and 61.2 mL, respectively. According to the IEJS, there were 6 circular stapler (CS) (single and double stapling techniques) and 26 linear stapler (LS) (overlap technique and functional end-to-end anastomosis) procedures performed. Two patients, who had undergone IEJS by double stapling technique, developed anastomotic stenosis and required endoscopic balloon dilatations of the anastomotic sites. Therefore, we changed to LS to secure the abundant anastomotic diameter. In our institute, some problematic complications in the IEJS procedure occurred at the introduction of the TLTG. We have overcome these complications by changing and standardizing the IEJS techniques, and by cultivating the laparoscopic techniques. PMID- 27358527 TI - Applications of Basic Physics for a Surgeon. PMID- 27358528 TI - Foam Sclerotherapy-Simple Solution for Difficult Problem. PMID- 27358529 TI - Cardiovascular complications among individuals with amphetamine-positive urine drug screening admitted to a tertiary care hospital in Riyadh. AB - BACKGROUND: Amphetamine-type stimulants (ATS) are the most commonly used illicit drugs in Saudi Arabia. Frequency and outcome of ATS-related cardiovascular (CV) complications in the Saudi community have not been previously studied. AIM: We aimed to determine the incidence and the clinical outcomes of CV complications among individuals with amphetamine-positive urine drug screening (APUDS) tests admitted to a tertiary care facility in Riyadh, Saudi Arabia. METHODS: Retrospective review of consecutive cases with APUDS and concurrently positive cardiac biomarkers admitted to King Abdul-Aziz Medical City in Riyadh, Saudi Arabia, between January 2006 and December 2013. The laboratory database was queried to identify patients with positive APUDS and abnormal cardiac biomarkers. Clinical data were extracted from the electronic medical records. RESULTS: A total of 7450 urine drug screening tests were performed during the study period, out of which 720 (9.6%) were positive for ATS (APUDS group). Forty-two cases in the APUDS group were documented to have CV complications. All cases were men with a median age of 39 years (range, 21-60 years). Acute coronary syndrome/myocardial infarction was the most frequent clinical presentation (n = 31, 74%), predominantly in the form of ST-elevation myocardial infarction. Other less frequent complications included myopericarditis, cardiomyopathy, and arrhythmia. Coronary procedures were performed in 30 cases. Median hospital stay was 5 days (range, 1-28 days) and in-hospital mortality was 7.2%. CONCLUSION: APUDS is frequently encountered in young Saudi men presenting to the emergency department of our institution. Individuals with APUDS are at increased risk of CV complications and in-hospital mortality. The most frequent APUDS-related CV complication is acute coronary syndrome. PMID- 27358530 TI - The prevalence and the clinical characteristics of metabolic syndrome patients admitted to the cardiac care unit. AB - OBJECTIVES: Metabolic syndrome (MetS) is a group of multiple cardiovascular risk factors, including dysglycemia, central obesity, high cholesterol, and hypertension. Cardiovascular disease is one of the most common complications of MetS. Recent studies showed that prevalence of MetS among patients admitted with acute coronary syndrome was as high as 46%. DESIGN: We conducted a cross sectional study of 203 patients at the two main hospitals in Ta'if, Saudi Arabia. Patients older than 18 years who were admitted to the Cardiac Care Unit (CCU) between the months of August 2013 and June 2014 were asked to participate. MetS diagnosis was made based on the International Diabetes Federation definition. RESULTS: A total of 203 patients participated, with 59.1% male and 40.9% were female. The mean age was 60.9 years with a mean body mass index of 28.97 kg/m(2) and a mean waist circumference of 95.45 cm. The prevalence of MetS was 47.8%, primarily among obese female patients who reported sedentary lifestyles. Additionally, MetS patients were more likely to be admitted with heart failure (p < 0.05) and more likely to have moderate-to-severe left-ventricular hypertrophy (LVH; p < 0.05) relative to non-MetS patients. CONCLUSION: Of the patients admitted to the CCU, 47.8% had MetS, with those patients likely to be female and obese. Furthermore, MetS patients were more likely to be admitted with heart failure and suffer from moderate-to-severe LVH. PMID- 27358531 TI - Cystatin C: A prognostic marker after myocardial infarction in patients without chronic kidney disease. AB - AIMS: Cystatin C is an endogenous marker of renal function. It is a well established better marker of glomerular filtration rate than serum creatinine. There is also evidence that cystatin C is associated with atherosclerotic disease. The present prospective study evaluated the prognostic value of cystatin C after myocardial infarction in patients without chronic kidney disease. METHODS AND RESULTS: A total of 127 patients who underwent coronary angiography after an acute coronary syndrome (ACS) were included. Cystatin C was associated with the severity of coronary artery disease (CAD). Cystatin C levels were significantly higher in patients with 3-vessels disease and severe CAD according to GENSINI score (p = 0.01 and p < 0.001 respectively). Among the patients admitted for ST elevation myocardial infarction, Cystatin C concentration was correlated with the initial TIMI flow in the culprit artery (p < 0.001). Mean duration of the follow up period was 10.76 +/- 2.1 months. High Cystatin C concentrations were associated to the occurrence of unfavourable outcomes and cardiovascular mortality during follow-up (1.19 +/- 0.4 vs. 1.01 +/- 0.35 mg/L, p = 0.01 and 1.21 +/- 0.36 vs. 0.96 +/- 0.27 mg/L, p = 0.03). Among different laboratory parameters, cystatin C was the best marker to predict the occurrence of major adverse cardiovascular events during the follow-up (Area under the receiveroperating characteristic curve = 0.743). CONCLUSION: High cystatin C levels are associated with the severity of coronary artery disease in patients presenting an acute coronary syndrome and a normal renal function. Cystatin C is also associated to unfavourable cardiovascular outcomes during follow-up and appears as a strong predictor for risk of cardiovascular events and death. PMID- 27358532 TI - Red cell distribution width and neutrophil-to-lymphocyte ratio predict left ventricular dysfunction in acute anterior ST-segment elevation myocardial infarction. AB - OBJECTIVES: Red cell distribution width (RDW) and neutrophil-to-lymphocyte ratio (NLR) are the two markers used to determine risk of mortality and adverse cardiovascular outcomes in patients with acute myocardial infarction. The relationship between RDW, NLR, and left ventricular (LV) systolic functions has not been reported. In this report, we aimed to investigate the relationship between RDW, NLR, and LV systolic function in anterior ST-segment elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (PCI). METHODS: RDW and NLR were measured on admission in 106 STEMI patients treated with primary PCI. Patients were divided into two groups according to left ventricular ejection fraction (LVEF), as Group I (systolic dysfunction, LVEF <50%) and Group II (preserved global left ventricle systolic function, LVEF ?50%). The first group included 47 patients and the second group included 59 patients. RESULTS: Mean RDW and NLR were significantly higher in Group I compared to Group II [13.7 +/- 0.9% vs. 13.4 +/- 0.7%, p = 0.03 and 5.86 (range, 0.66-40.50) vs. 2.75 (range, 0.51-39.39), p = 0.013, respectively]. CONCLUSION: Increased RDW and NLR on admission, in anterior STEMI patients treated with primary PCI are associated with LV systolic dysfunction. PMID- 27358534 TI - An alien in the heart. AB - We report a case of a 38-year-old-man who presented with altered mental status. The patient was diagnosed with infective endocarditis (IE) originating from the GORE HELEX septal occluder device, which was placed 15 months earlier for symptomatic atrial septal defect. Brain imaging revealed shower emboli phenomena from the known IE. The patient developed hydrocephalus for which external ventriculostomy was performed. Improved neurological status warranted open heart surgery. The patient was later confirmed to be an intravenous drugs abuser, prejudicing IE. This case highlights the importance of meticulously monitoring patients with suspected high-risk behavior with an implanted intracardiac prosthetic device. PMID- 27358535 TI - Intracardiac tumor causing left-ventricular outflow-tract obstruction in a newborn. AB - The following report describes the case of newborn girl with an asymptomatic systolic murmur, which on imaging revealed a nearly obstructive mass in the left ventricular outflow tract. The mass was resected and found to be consistent with a rhabdomyoma. Here, we describe the pathologic and clinical characteristics of this tumor. PMID- 27358533 TI - Assessment of left ventricular mass index could predict metabolic syndrome in obese children. AB - BACKGROUND: Childhood obesity is a major risk factor for cardiovascular diseases in children and adults. OBJECTIVES: The purpose of this study was to evaluate the serum leptin level and the cardiac changes in normotensive obese children and to study the relationship between left ventricular mass index (LVMI) and serum leptin with the parameters of metabolic syndrome (MS) in obese children. METHODS: This study was conducted in al Jeddani Hospital and Ibn Sina College Hospital in Saudi Arabia in the period from July 2012 to December 2013, and included 82 obese children. Their mean age was 10.2 +/- 2.8 years; they were divided into 25 obese children with MS and 57 obese children without MS, and 40 healthy age- and sex matched children were also included in the study as a control group. All children were subjected to clinical assessment including standing height, body weight, body mass index (BMI), waist circumference (WC), and blood pressure measurements. All children received an echocardiographic examination (2-dimensional, M-mode, Doppler, and tissue Doppler echocardiograpy) and laboratory assessment of serum leptin level, fasting glucose, fasting insulin, the homeostatic model assessment for insulin resistance (HOMA) index, total cholesterol, triglycerides, and high- and low-density lipoprotein profile. RESULTS: BMI, BMI standard deviation score, WC, fasting glucose, fasting insulin, HOMA index and the serum leptin level were significantly higher in obese children compared to control group (p < 0.05). The LVMI were increased in the obese compared to the control group (p < 0.001) while left ventricle systolic and diastolic functions did not differ in obese versus control group (p > 0.05). There was a significant positive correlation between both LVMI and serum leptin level in comparison to BMI, WC, fasting glucose, fasting insulin, HOMA, triglycerides, and low-density lipoprotein in all obese children, especially the MS group. However, there was a significant negative correlation between both LVMI and serum leptin level in comparison to high density lipoprotein. CONCLUSION: Assessment of LVMI as routine echocardiographic examinations and serum leptin level might be a feasible and reliable method for the evaluation of obesity and its related cardiovascular risks during childhood that can predict metabolic syndrome and insulin resistance. PMID- 27358536 TI - Development of neoaortic pseudoaneurysm after arterial switch operation. AB - We report a case of a 46-day-old boy who was diagnosed with transposition of the great arteries and underwent arterial switch operation. A large neoaortic pseudoaneurysm was diagnosed on the first postoperative follow up. Successful repair of the aneurysm was done and at the 3-year follow up, the child's clinical and imaging findings remain normal. PMID- 27358537 TI - A rare cause of recurrent aortic dissection. AB - We report the case of a 19-year-old man with a history of Loeys-Dietz syndrome (LDS), which was diagnosed when he had a Stanford type A aortic dissection. He also had multiple aneurysms including ones in the innominate, right common carotid, and right internal mammary arteries. He had had multiple procedures including Bentall's procedure, repeat sternotomy with complete arch and valve replacement, and coil embolization of internal mammary artery aneurysm in the past. His LDS was characterized by gene mutation for transforming growth factor beta receptor 1. He presented to our facility with sudden onset of back pain, radiating to the right shoulder and chest. He was diagnosed with Stanford type B aortic dissection and underwent thoracic aorta endovascular repair for his aortic dissection. This case represents the broad spectrum of pathology associated with LDS where even with regular surveillance and aggressive medical management the patient developed Stanford B aortic dissection. PMID- 27358538 TI - Acute myocardial infarction with multiple coronary thromboses in a young addict of amphetamines and benzodiazepines. AB - A 35-year-old man of average build and a smoker, with a background of a psychiatric disorder, was brought by his neighbor to the emergency department after an hour of severe chest pain. Upon arrival at the hospital he had cardiac arrest, was resuscitated, and moved to the catheterization laboratory with inferior, posterior, and lateral myocardial infarction. Coronary angiography showed an unusual thrombosis in multiple coronary branches. Toxicology report showed high levels of amphetamines and benzodiazepines in the patient's original blood sample. The patient was kept under ventilation for 18 days, with difficult recovery due to severe withdrawal manifestations, ventilation acquired pneumonia, and rhabdomyolysis inducing acute renal failure. The patient regained near normal left ventricular function after baseline severe regional and global dysfunction. We postulate a relationship between the use of amphetamines, potentiated by benzodiazepines, and occurrence of acute thrombosis of multiple major coronary arteries. PMID- 27358539 TI - The Challenge of Childhood Cancer in Developing Countries. PMID- 27358540 TI - Methylene Blue as a Diagnostic Aid in the Early Detection of Potentially Malignant and Malignant Lesions of Oral Mucosa. AB - BACKGROUND: In vivo stains are the prompt resources, which have emerged in recent years to aid as clinical diagnostic tools in detecting early potentially malignant and malignant lesions. Toluidine blue, by its property of retaining in the increased DNA and RNA cellular activity areas, aids in delineating the suspicious areas. However, it is hazardous if swallowed, and has been shown to have toxicity to fibroblasts. Methylene blue has a similar chemical structure and exhibits similar physicochemical properties as toluidine blue. It is less toxic to the human body and has recently been proposed for screening some gastrointestinal or prostate tumors. The application of this material in detecting oral lesions has so far not been addressed. The objective of this study was to evaluate the sensitivity and reliability of in vivo staining with methylene blue as a diagnostic adjunct in screening for oral malignant or potentially malignant lesions. METHODS: The present study involved the examination of 75 patients suspected of having oral malignant or potentially malignant lesions by methylene blue staining. The results of methylene blue uptake were compared with a simultaneous biopsy of these lesions. RESULTS: The overall sensitivity was 95% (100% for malignancy and 92% for potentially malignant lesions) and specificity was 70%. The positive predictive value was 91% and negative predictive value of 80% was observed in the study. CONCLUSION: We consider that methylene blue staining is a useful diagnostic adjunct in a large, community-based oral cancer screening program for high-risk individuals. PMID- 27358541 TI - Prevalence of Tobacco Consumption and Its Contributing Factors among Students of a Private Medical College in Belgaum: A Cross Sectional Study. AB - BACKGROUND: Tobacco consumption epidemic is one of the biggest public health threats that the world is facing and attracts the attention of researchers to identify the cause for the same in specific groups. Medical students act as mentors to fight against tobacco use, but several reports suggest that a good number of medical undergraduates are themselves addicted to tobacco use. Thus, the objective of the study was to determine the prevalence of tobacco consumption and its association with various factors among undergraduate medical students. MATERIALS AND METHODS: A cross-sectional study was conducted on 372 undergraduate medical students from first to fourth year during November 2013 to January 2015. A pre-designed, pre-tested, structured and self-administered questionnaire was used. Statistical analysis was done using SPSS software version 16. Data was analyzed for percentage, Chi-square test and regression analysis to find association between tobacco use and various independent variables. RESULT: The mean age of the participants was 21.2 (SD=2.28) years with a male-female ratio of 1.92:1. The prevalence of tobacco use was 27.1% (n=101). The overall prevalence of smoking and smokeless tobacco use was 22.6% (n=84) and 7.8% (n=29) respectively. The prevalence of current tobacco use was 24.2% (n=90). Among the ever tobacco users, about 3% (n=11) had quit using tobacco. Tobacco consumption was observed to be significantly associated with male gender (p<.001), increasing age (p<0.01), residing in hostels (p<.001) and with a parental history of using tobacco (p<.001). CONCLUSION: The prevalence of tobacco use in smoking and smokeless form among undergraduate medical students was high.This has important implications in the strict implementation and monitoring of smoking-related rules in hostels of medical colleges, especially those related to peer-support. PMID- 27358542 TI - Prevalence of Malnutrition and Associated Factors among Hospitalized Patients with Acquired Immunodeficiency Syndrome in Jimma University Specialized Hospital, Ethiopia. AB - BACKGROUND: HIV/AIDS predisposes to malnutrition. Malnutrition exacerbates HIV/AIDS progression resulting in increased morbidity and mortality. The magnitude of malnutrition in HIV/AIDS patients has not been well studied in Ethiopian setup. Our objective was to assess the prevalence of malnutrition and associated factors among HIV/AIDS patients admitted to Jimma University Specialized Hospital (JUSH). METHOD: A cross-sectional study was conducted to assess the nutritional status of 109 HIV/AIDS patients admitted from November 2013 to July 2014. Cohort design was also used for outcome assessment. Serum levels of hemoglobin, albumin and CD4 counts were determined. Data were organized, coded, cleaned, entered into a computer and analyzed using SPSS version 16.0. Descriptive analysis was done initially. Those variables in the bivariate analysis with P-value < 0.25 were then considered as candidates to be included in the multivariable logistic regression model. A P-vale of < 0.05 was considered as statistically significant. RESULTS: The mean age of the patients was 32.7+/-8.12 with male to female ratio of 1:1.9. Patients were in either clinical stage, 3(46.8%), or stage, 4(53.2%). Forty nine (45%) of the respondents had a CD4 count of < 200 cells/uL. The overall prevalence of malnutrition was 46.8% (BMI<18.5kg/m2) and 44.1% (MUAC<= 20cm). Eighty four (77.1%) of the patients had a serum albumin level of <=3.5g/dl while 76 (69.6%) of the patients had anemia (Hg<12g/dl). CONCLUSION: The prevalence of malnutrition was found to be high. WHO Stage 4 disease and CD4 count <200cells/ul were independent predictors of malnutrition. PMID- 27358543 TI - Knowledge about Radiation Related Health Hazards and Protective Measures among Patients Waiting for Radiologic Imaging in Jimma University Hospital, Southwest Ethiopia. AB - BACKGROUND: Radiologic diagnostic and therapeutic procedures using ionizing radiation carry potential health risks. Hence, clients' knowledge about radiation would play a key role in reducing unnecessary imaging and its impacts. However, information on client's knowledge in low income countries specifically in the Ethiopian context has been was limited. Therefore, the aim of this study was to assess knowledge about radiation related hazards and protective measures among patients waiting for radiologic imaging. METHODS: Descriptive cross sectional study design was employed on 388 patients waiting for radiologic imaging in Jimma University Hospital from Dec.25/2014 to Jan. 10/2015. Eligible participants were interviewed using pretested questionnaire. Data were entered and analyzed using IBM SPSS version 21. A descriptive analysis was conducted to get summary values of clients' radiation related knowledge. RESULTS: A total of 386 clients were included to the analysis.Two hundred and three (52.6%) participants had ever heard radiation related health hazards. Among these, 74.9% mentioned infertility, 64.0% indicated cancer followed by 26.6% who mentioned cataract as radiation related health hazards. A large number of clients (75.6%) had no idea about radiation protective measures, whereas 22% of them mentioned not entering examination room unless ordered by health professionals and 10.6% indicated covering sensitive body parts with lead (pb). The majority (85.8%) of the clients did not support unjustified repeated radiation imaging for diagnostic or other purposes. CONCLUSION: The overall knowledge of clients about radiation imaging seems inadequate. Thus, comprehensive awareness raising programmes targeted at different settinsg and levels should be designed and implemented. PMID- 27358544 TI - Mean Normal Portal Vein Diameter Using Sonography among Clients Coming to Radiology Department of Jimma University Hospital, Southwest Ethiopia. AB - BACKGROUND: Mean portal vein diameter is considered as the best indicator for portal hypertension. However, the cutoff point differs from study to study (above 10-15 mm) despite the existence of normal mean portal vein diameter between 10-15 mm in different settings.This implies the existence of limited evidence on normal portal vein diameter for all populations in all countries prior to setting the cutoff points. Therefore, the aim of this study was sonographic assessment of normal mean portal vein diameter among patients referred to The Department of Radiology in Jimma University Hospital. METHODS: A facility based cross-sectional study was conducted from November to December 2014 at Jimma University Hospital on a total of 195 clients. Data about portal vein diameter for eligible clients were collected by radiologists using Sonography. Data were edited manually, entered and analyzed using SPSS version 16. RESULT: Data were collected from a total of 195 participants. Among these, 121(62.1%) were males and the median age of the participants was 35 years. The study revealed a normal mean portal vein diameter of 10.6 mm +/-1.8 SD with a respirophasic variation of 25.6%. Likewise, the normal mean portal vein diameter seemed to have varied significantly by age and sex. CONCLUSION: The study revealed a normal mean portal vein diameter ranging below 13 mm. Hence, decisions made in clinical settings should base on these findings. Besides, there is a need for large scale study to determine portal vein diameter variation by age and sex, controlling other confounders. PMID- 27358545 TI - Prevalence and Predictors of "Small Size" Babies in Ethiopia: In-depth Analysis of the Ethiopian Demographic and Health Survey, 2011. AB - BACKGROUND: Low Birth Weight (LBW) babies account for nearly 80% of neonatal deaths globally. In Ethiopia, only 5% of them are weighed at birth. This study analyzes the prevalence and key proximate determinants of reported infant size, and its validity to use as a proxy indicator for low birth weight inthe Ethiopian context. METHODS: In-depth analysis of the Ethiopian Demographic and Health Survey dataset was conducted using representative data collected from all regions in the country. Considering reported fetal size at birth as an outcome variable, key predicting variables from socio-demographic, household, child and obstetric characteristics were employed for analyses. Chi-square test and multivariate logistic regression model were used to determine predictors at p value < 0.05. RESULTS: An average of 29.1% of Ethiopian babies were reported "small" at birth in 2011. various variables from socio-demographic, household, child and maternal reproductive characteristics were identified as key predictors. Women who develop anemia and not attending antenatal care during pregnancy had 15% and 41% more risk of giving birth to the reported "small size" babies than their counterparts (AoR = 1.15, and 1.41, 95% CI (1.02, 1.64 and 1.06, 1.88) respectively. Maternal age at delivery, maternal literacy level, paternal educational status and presence of radio or television in the household and other factors were also other key predictors identified. CONCLUSION: The prevalence of small size babies in Ethiopia is high but comparable to regional estimates of LBW. It is recommend that improving maternal nutritional and socio-economic status is a timely intervention to tackle the problem. PMID- 27358546 TI - Point-of-Care Testing for Anaemia in Children Using Portable Haematocrit Meter: A Pilot Study from Southwest Nigeria and Implications for Developing Countries. AB - BACKGROUND: Prompt and accurate diagnosis is needed to prevent the untoward effects of anaemia on children. Although haematology analyzers are the gold standard for accurate measurement of haemoglobin or haematocrit for anaemia diagnosis, they are often out of the reach of most health facilities in resource poor settings thus creating a care gap. We conducted this study to examine the agreement between a point-of-care device and haematology analyzer in determining the haematocrit levels in children and to determine its usefulness in diagnosing anaemia in resource-poor settings. METHODS: EDTA blood samples collected from participants were processed to estimate their haematocrits using the two devices (Mindray BC-3600 haematology analyzer and Portable Mission Hb/Haemotocrit testing system). A pairwise t-test was used to compare the haematocrit (PCV) results from the automated haematology analyzer and the portable haematocrit meter. The agreement between the two sets of measurements was assessed using the Bland and Altman method where the mean, standard deviation and limit of agreement of paired results were calculated. RESULTS: The intraclass and concordance correlation coefficients were 0.966 and 0.936. Sensitivity and specificity were 97.85% and 94.51% respectively while the positive predictive and negative predictive values were 94.79% and 97.73%. The Bland and Altman's limit of agreement was -5.5-5.1 with the mean difference being -0.20 and a non-ignificant variability between the two measurements (p = 0.506). CONCLUSION: Haematocrit determined by the portable testing system is comparable to that determined by the haematology analyzer. We therefore recommend its use as a point-of-care device for determining haematocrit in resource-poor settings where haematology analyzers are not available. PMID- 27358547 TI - Pharmaceutical Regulatory Framework in Ethiopia: A Critical Evaluation of Its Legal Basis and Implementation. AB - BACKGROUND: Effective and enforceable national regulations describing the manufacture and (re)packaging, export and import, distribution and storage, supply and sale, information and pharmaco-vigilance of medicines are required to consistently ensure optimal patient benefit. Expansion of pharmaceutical industries in many countries with advancement in transport technologies facilitated not only trade of genuine pharmaceutical products but also the circulation of poor quality medicines across the globe. In Ethiopia, even though "The Pharmacists and Druggists Proclamation No 43/1942" was used to regulate both the professions and the facilities where they were practiced, comprehensive regulation of the pharmaceutical market was introduced in 1964 by a regulation called "Pharmacy Regulation No. 288/ 1964". This legislation formed the legal basis for official establishment of drug regulation in the history of Ethiopia, enabling the regulation of the practice of pharmacists, druggists and pharmacy technicians; manufacturing, distribution, and sale of medicines. In June 1999, a new regulation called the "Drug Administration and Control Proclamation No. 176/1999" repealed most parts of the regulation 288/1964. The law established an independent Drug Administration and Control Authority (DACA) with further mandate of setting standards of competence for licensing institutions/facilities. DACA was re-structured as Food, Medicine and Health Care Administration and Control Authority (EFMHACA) of Ethiopia by the "Proclamation No. 661/2009" in 2010 bearing additional responsibilities like regulation of food, health care personnel and settings. The mere existence of this legal framework does not guarantee complete absence of illegal, substandard and falsified products as well as illegal establishments in the pharmaceutical chain. Therefore, the objective of the research is to assess the pharmaceutical regulatory system in Ethiopia and to reveal possible reasons for deficiencies in the pharmaceutical chain. METHODS: An archival review, an in-depth interview of key informants and an institutions based cross-sectional survey study were conducted during March to April 2013. The comprehensiveness of the pharmaceutical law to protect public health relative to three selected African countries (South Africa, Tanzania and Uganda) and European Union, and implementation was assessed. RESULTS: The study revealed that Ethiopia does have a written national drug policy upon which the Medicines Regulatory Proclamation 661/2009 is based. According to this proclamation, the Ethiopian The Food, Medicines and Healthcare Administration and Control Authority is mandated to execute the regulatory activities as per the council of ministers regulation 189/2010. The legal framework for pharmaceutical regulation of Ethiopia was founded to fulfill all the medicines regulatory functions potentially enabling to combat illegal, substandard and falsified medicines and illegal establishments. Moreover, all the key informants witnessed that the government is commited and proclamation 661/2009 is comprehensive, but they stressed the compelling need of regulatory tools for effective implementation. From the institution-based cross sectional study, it was revealed that there exist illegal sources formedicine in the pharmaceutical market. The main reasons for their existence were regulatory factors including weak regulatory enforcement (64.5%), lack of informal market control (60.8%), weak port control (50.0%), and poor cooperation between executive bodies (39.6%); and resource constraint (27.8%), which is an institutional factor. CONCLUSIONS: From legislative point of view, the medicines regulatory framework in Ethiopia fulfils all regulatory functions required for effective medicines regulation. However, the existence of the legislation by its own is not a guarantee to prevent the existence of unauthorized/illegal medicine sources since this requires effective implementation of the legislation, which is in fact affected by the governments political commitment, resource and intergovernmental cooperation. PMID- 27358548 TI - Establishing Medical Schools in Limited Resource Settings. AB - INTRODUCTION: One urgent goal of countries in sub-Saharan Africa is to dynamically scale up the education and work force of medical doctors in the training institutions and health facilities, respectively. These countries face challenges related to the rapid scale up which is mostly done without proper strategic planning, without the basic elements of infrastructure development, educational as well as academic and administrative human resources. Medical education done in the context of limited resources is thus compromising the quality of graduates. In the future, a collaborative and need-based approach involving major stakeholders such as medical educators concerned, ministries, planners and policy makers is needed. GOAL: This article identifies the challenges of establishing medical schools and sustaining the quality of education through rapid scale-up in Sub-Saharan Africa in the settings of limited resources. It also outlines the minimum requirements for establishing medical schools. METHODS: A consensus building workshop was conducted in Bishoftu, Ethiopia, from Nov 8-12, 2013. Participants were professionals from 13 Ethiopian medical schools, and representatives of medical schools from South Sudan, Somaliland, Somalia, and Mozambique. Participants are listed in Appendix 1. RECOMMENDATIONS: The governments and stakeholders should jointly develop strategic plans and a roadmaps for opening or expanding medical schools to scale up educational resources. It is advisable that medical schools have autonomy regarding the number of student-intake, student selection, curriculum ownership, resource allocation including for infrastructure and staff development. Health science and medical curricula should be integrated within and harmonized nationally. An educational evaluation framework needs to be embedded in the curricula, and all medical schools should have Health Science Education Development Centers. PMID- 27358549 TI - Combined Open-Heart Coronary Artery Bypass Surgery and Subtotal Thyroidectomy in a 54-year-old patient: A Case Report. AB - BACKGROUND: Combined open-heart surgery and thyroidectomy is a rare procedure. However, some difficulties will occur for cardiac surgery when thyromegaly extends into the retrosternal space. CASE DETAILS: A 54-year-old woman suffering from dyspnea, chest pain and decreased left ventricular function (EF=40%) was diagnosed with coronary artery disease (3 vessel disease) and became candidate for coronary artery bypass grafting (CABG). Also, she had multinodular goiter with normal thyroid function test. After midsternotomy, a huge goiter was seen in the upper mediastinum. Because the mass had covered the ascending aorta and involved the posterior aspect of the innominate vein making access to aorta impossible, thyroidectomy was performed at first followed by CABG. Post-operation course was satisfactory. Fourteen months later, the patient was euthyroid and in NYHA class 1. CONCLUSION: The evidence of the case showed that combined CABG and thyroidectomy can be performed safely. PMID- 27358550 TI - Acanthamoeba Infection in a Drowning Child. AB - BACKGROUND: Acanthamoeba infection is a potential life-threatening complication of drowning. The management of drowning-associated Acanthamoeba infection remains controversial. Survival reports on Acanthamoeba infection have been on case reports only. CASE DETAILS: A 2-year-old, previously healthy Indonesian boy presented with decreased consciousness and inadequate breathing, followingdrowning. The event was unsupervised with unknown estimated time of submersion. Resuscitation was commenced and mechanical ventilated was applied. Sputum specimen revealed alive Acanthamoeba with pseudopods and cysts. Sputum culture resulted in Pseudomonas aeruginosa and cerebrospinal fluid was supportive for Acanthamoeba with 1-3 trophozoites and cyst. Imaging of the head showed cerebral edema and encephalitis. The patient received intravenous ceftazidime, metronidazole, fluconazole and rifampicin. The patient's consciousness was unsatisfactory regained resulting in an altered mental status. CONCLUSION: No treatment so far has given a succesful outcome for Acanthamoeba. In this case, management with metronidazole, rifampicin and fluconazole showed regain of consciousness resulting in altered mental status. PMID- 27358551 TI - A Tricuspid Valve Mass Attached to Papillary Muscle. AB - BACKGROUND: Cardiac myxoma is the most common benign heart tumor which can arise in any of the cardiac chambers, valves or related great veins. Diagnosis of a myxoma arising from the tricuspid valve apparatus is exceptional. We present a rare case of myxoma in a tricuspid valve attached to papillary muscle. CASE DETAILS: A 45-year-old man was referred to our center for the evaluation dyspnea and chest pain. During work-up by transthoracic echocardiography (TTE), a mass was found on the corda tendinea of the anterior papillary muscle of the tricuspid valve. Coronary angiography revealed normal coronary artery. During open heart surgery, an oval and non-pedunculated mass was detected on tricuspid corda tendinea and resected. Pathological examination revealed the presence of a myxoma. CONCLUSION: This experience illustrates a rare case of myxoma which originated from tricuspid corda tendinea, diagnosed by echocardiography, suggesting fibroelastoma. However, the mass was not clear enough but dyspnea and sign and symptom of probably embolization to lung urged us to treat it surgically. No complications attributable to the mass developed in the postoperative course. In the first year of follow-up, non-recurrence of the mass was detected on TEE, and the patient was asymptomatic. PMID- 27358552 TI - Immune Reconstitution Inflammatory Syndrome and Shingles Associated with a Combined Paralysis of Three Oculomotor Nerves: A Case Report. AB - BACKGROUND: In countries with high prevalence of HIV/AIDS infection, particularly in black Africa, shingles is one of the main opportunistic infections during immunosuppression due to AIDS in young patients. If immunological weakness is important, usually when the CD4 cell count is less than 100 cells/mm(3), the risk of inflammatory reactions in the first three months after initiating of antiretroviral treatment (ART) is very high. This inflammatory reaction is called immune reconstitution inflammatory syndrome (IRIS). This observation reports the first documented case of IRIS with V1 shingles in a young HIV patient at University Hospital of Brazzaville. CASE DETAILS: A 40 years old patient was seen for a pain of the right side of the face and a complete immobility of the eyeball. The diagnosis of V1 shingles with a pan uveitis, and a paralysis of III, IV and VI nerves was made. The patiants HIV status was positive and CD4 cell count was 150 cells/mm(3). After two months of evolution under ART with a CD4 count of 850 cells /mm(3), the symptomatology was quickly complicated by significant inflammation causing a phtisis bulbi. CONCLUSION: CD4 cells count is an important indicator in the HIV/AIDS therapy. In some major forms of IRIS, momentary pause of anti retroviral treatment is sometimes necessary. PMID- 27358553 TI - Tuberculous Dactylitis: An Uncommon Presentation of Skeletal Tuberculosis. AB - BACKGROUND: Skeletal involvement accounts 1-5% of all cases of Tuberculosis. The vertebrae are more commonly affected. The bones of the hands are more affected than the bones of the feet. The term "spina ventosa" has been used to describe this disorder because of its radiographic features of cystic expansion of the involved short tubular bones. Tuberculous dactylitis mainly occurs through lympho hematogenous spread. The lung is the primary focus in 75% of cases. CASE DETAILS: A 4 years old female child developed a painless swelling on her left index finger two months prior to her presentation. Following an unsuccessful treatment as a case of osteomyelitis with antibiotics, imaging showed an expansile lytic lesion with sclerosis, and fine needle aspiration confirmed tuberculous dactylitis. The child was initiated on anti-tubercular treatment with subsequent marked clinical and radiologic improvement. CONCLUSION: Presence of longstanding finger swelling and pain should alert a clinician to consider active disseminated tuberculosis. Furthermore, proper interpretation of imaging and use of fine needle aspiration has been highlighted. PMID- 27358554 TI - Laboratory assessment of thermal characteristics of three phacoemulsification tip designs operated using torsional ultrasound. AB - PURPOSE: Ultrasound activation of phacoemulsification (phaco) tips can create considerable thermal energy that may increase the risk of tissue damage during cataract surgery. The purpose of this study was to define the thermal profiles of three phaco tip designs in simulated surgical conditions. METHODS: In this laboratory investigation, sleeved phaco tips (mini-flared Kelman((r)) tip with aspiration bypass port and Intrepid((r)) Balanced Tip with aspiration bypass port, and MST A1 bent-mini phaco tip (without aspiration bypass) were tested using an ultrasonic phaco device operated in torsional mode at power levels of 50%, 75%, and 100% amplitude. An automated fixture applied a 30 g load to simulate compression against the incision site, leading to friction between the silicone sleeve and the titanium tip. Temperature was recorded by high rate infrared imaging under conditions of free flow and occlusion, which was simulated by clamping the aspiration line. Data were summarized using descriptive statistics. RESULTS: Baseline temperatures of ~26 degrees C were observed for all tips. During ultrasonic operation at 50%, 75%, and 100% amplitude, temperatures were lower for the mini-flared and balanced tips versus the bent-mini tip, both when load was applied and during occlusion. The bent-mini tip reached temperatures as high as 70 degrees C during occlusion with load when operated at 100% amplitude, whereas the mini-flared tip remained <50 degrees C, and the balanced tip remained <36 degrees C in all test conditions. For the mini-flared and balanced tips, temperature increases during operation were not markedly different from free flow and no-load conditions when occlusion or frictional events were simulated. CONCLUSION: In all experiments for each tip design, increasing ultrasound power was associated with greater increases in tip temperature. Tip temperatures increased with applied load, but marked temperature increases during occlusion were observed only with the bent-mini tip. The balanced tip produced minimal thermal peaks in all tests. PMID- 27358555 TI - Flavokawain derivative FLS induced G2/M arrest and apoptosis on breast cancer MCF 7 cell line. AB - Known as naturally occurring biologically active compounds, flavokawain A and B are the leading chalcones that possess anticancer properties. Another flavokawain derivative, (E)-1-(2'-Hydroxy-4',6'-dimethoxyphenyl)-3-(4-methylthio)phenyl)prop 2-ene-1-one (FLS) was characterized with (1)H-nuclear magnetic resonance, electron-impact mas spectrometry, infrared spectroscopy, and ultraviolet ((1)H NMR, EI-MS, IR, and UV) spectroscopic techniques. FLS cytotoxic efficacy against human cancer cells (MCF-7, MDA-MB-231, and MCF-10A) resulted in the reduction of IC50 values in a time- and dose-dependent mode with high specificity on MCF-7 (IC50 of 36 MUM at 48 hours) against normal breast cell MCF-10A (no IC50 detected up to 180 MUM at 72 hours). Light, scanning electron, and fluorescent microscopic analysis of MCF-7 cells treated with 36 MUM of FLS displayed cell shrinkage, apoptotic body, and DNA fragmentation. Additionally, induction of G2/M cell arrest within 24 hours and apoptosis at subsequent time points was discovered via flow cytometry analysis. The roles of PLK-1, Wee-1, and phosphorylation of CDC-2 in G2/M arrest and proapoptotic factors (Bax, caspase 9, and p53) in promotion of apoptosis of FLS against MCF-7 cells were discovered using fluorometric, quantitative real-time polymerase chain reaction, and Western blot analysis. Interestingly, the presence of SCH3 (thiomethyl group) on ring B structure contributed to the selective cytotoxicity against MCF-7 cells compared to other chalcones, flavokawain A and B. Overall, our data suggest potential therapeutic value for flavokawain derivative FLS to be further developed as a new anticancer drug. PMID- 27358556 TI - Efficacy and safety of gemcitabine plus erlotinib for locally advanced or metastatic pancreatic cancer: a systematic review and meta-analysis. AB - BACKGROUND: Pancreatic cancer is considered as a chemoresistant neoplasm with extremely dismal prognosis. Gemcitabine is recommended as the standard agent for locally advanced or metastatic pancreatic cancer. A series of trials have been conducted to improve the outcome of advanced pancreatic cancer with other anticancer drugs in combination with gemcitabine. Unfortunately, the designers of the clinical trials failed to improve the poor prognosis of patients with advanced pancreatic cancer. Erlotinib was the first additional drug that improved the overall survival of patients with advanced pancreatic cancer with gemcitabine. We performed this systematic review and meta-analysis to explore the efficacy and safety of the combination of gemcitabine with erlotinib (GemErlo) for patients with advanced pancreatic cancer using the currently available evidence. METHODS: PubMed/MEDLINE, EMBASE, the Cochrane Library, and relevant abstracts of major conferences were comprehensively searched. Data results on objective response rate, disease control rate, and 1-year survival were pooled by using MetaAnalyst with a random-effects model. Results on progression-free survival and overall survival were only summarized descriptively. RESULTS: A total of 24 studies with 1,742 patients with locally advanced or metastatic pancreatic cancer treated with GemErlo were included. Combined objective response rate was 14.4% (95% CI: 11.6%-17.7%), disease control rate was 55.0% (95% CI: 51.5%-58.5%), and 1-year survival rate was 28.5% (95% CI: 24.0%-33.4%). Progression-free survival ranged from 2.63 to 9.6 months, and overall survival varied from 6 to 10 months. As for the toxicity profile, the most common adverse events (AEs) were hematologic reactions, skin rash, and gastrointestinal reactions. Other severe AEs, which had low incidence, included treatment-induced death and interstitial lung disease. CONCLUSION: Our study showed that GemErlo is associated with reasonable activity in treating patients with locally advanced or metastatic pancreatic cancer. Most of the AEs were tolerable, while some severe AEs needed careful detection. PMID- 27358557 TI - Social support received by multidrug-resistant tuberculosis patients and related factors: a cross-sectional study in Zhejiang Province, People's Republic of China. AB - OBJECTIVES: The objective of this study is to assess the social support received by patients diagnosed with multidrug-resistant tuberculosis (MDR-TB) in Zhejiang Province, People's Republic of China and the factors that may have influenced it. METHODS: A total of 220 MDR-TB patients participated in the questionnaire-based survey, and the data from 212 valid questionnaires were analyzed. The respondents reported their sociodemographic status, disease features, and attitudes toward the disease. The social support rating scale was used to measure the patients' social support scores. An Independent Samples t-test, one-way analysis of variance, and a multiple linear regression model were used to analyze the related factors for the social support scores. RESULT: The average social support score of each MDR-TB patient was 32.56+/-7.86. Participants who were single, widowed or divorced, retired, and had fewer family members and lower family income were found to have lower social support scores. Participants unwilling to disclose their disease tended to have less social support (31.59<34.23, P=0.010). Participants who perceived great help from health care workers reported higher social support rating scale scores than those who perceived no help (35.36.29.89, P=0.014). CONCLUSION: MDR-TB patients in Zhejiang Province were shown to have a low level of social support. Patients who were not married, had smaller families, and lower family income received less social support, suggesting that family harmony could be an important source of social support. Patients' self-isolation may contribute to a decrease in the amount of support they receive from their surroundings. Health care organizations need to offer more social support to MDR TB patients. PMID- 27358558 TI - Effects of age, sex, and ethnicity on bone health status of the elderly in Kuala Lumpur, Malaysia. AB - BACKGROUND: Osteoporosis is a significant health problem in the developing countries and its prevalence data are important for the estimation of health care burden and policy making. This study aimed to determine the age-related changes in bone health and the prevalence of osteoporosis in males and females aged 50 years or above living in Kuala Lumpur, Malaysia. METHODS: A cross-sectional study was conducted between December 2014 and December 2015. Subjects answered a demographic questionnaire and underwent body anthropometric and bone health measurement. Assessment of bone health was performed using a quantitative ultrasound device that generated speed of sound, broadband ultrasound attenuation, stiffness index, and T-score based on stiffness index value as bone health indices. RESULTS: The prevalence of osteoporosis was 10.6% in males and 8.0% in females. Significant age-related decline of bone health indices (speed of sound, broadband ultrasound attenuation, stiffness index, and T-score) and a concurrent increase in the prevalence of osteoporosis and osteopenia were observed in females (P<0.05) but not in males (P>0.05). Ethnic differences in bone health indices and prevalence of osteoporosis/osteopenia were not observed (P>0.05). CONCLUSION: A significant proportion of males and females age 50 years or above have suboptimal bone health. Preventive measures such as early screening should be implemented to retard the progression of osteoporosis. PMID- 27358559 TI - Erratum: Effects of intravitreal ranibizumab on the untreated eye and systemic gene expression profile in age-related macular degeneration [Corrigendum]. AB - [This corrects the article on p. 357 in vol. 11, PMID: 27069359.]. PMID- 27358560 TI - Graphene oxide/multi-walled carbon nanotubes as nanofeatured scaffolds for the assisted deposition of nanohydroxyapatite: characterization and biological evaluation. AB - Nanohydroxyapatite (nHAp) is an emergent bioceramic that shows similar chemical and crystallographic properties as the mineral phase present in bone. However, nHAp presents low fracture toughness and tensile strength, limiting its application in bone tissue engineering. Conversely, multi-walled carbon nanotubes (MWCNTs) have been widely used for composite applications due to their excellent mechanical and physicochemical properties, although their hydrophobicity usually impairs some applications. To improve MWCNT wettability, oxygen plasma etching has been applied to promote MWCNT exfoliation and oxidation and to produce graphene oxide (GO) at the end of the tips. Here, we prepared a series of nHAp/MWCNT-GO nanocomposites aimed at producing materials that combine similar bone characteristics (nHAp) with high mechanical strength (MWCNT-GO). After MWCNT production and functionalization to produce MWCNT-GO, ultrasonic irradiation was employed to precipitate nHAp onto the MWCNT-GO scaffolds (at 1-3 wt%). We employed various techniques to characterize the nanocomposites, including transmission electron microscopy (TEM), Raman spectroscopy, thermogravimetry, and gas adsorption (the Brunauer-Emmett-Teller method). We used simulated body fluid to evaluate their bioactivity and human osteoblasts (bone-forming cells) to evaluate cytocompatibility. We also investigated their bactericidal effect against Staphylococcus aureus and Escherichia coli. TEM analysis revealed homogeneous distributions of nHAp crystal grains along the MWCNT-GO surfaces. All nanocomposites were proved to be bioactive, since carbonated nHAp was found after 21 days in simulated body fluid. All nanocomposites showed potential for biomedical applications with no cytotoxicity toward osteoblasts and impressively demonstrated a bactericidal effect without the use of antibiotics. All of the aforementioned properties make these materials very attractive for bone tissue engineering applications, either as a matrix or as a reinforcement material for numerous polymeric nanocomposites. PMID- 27358561 TI - Development, characterization, and in vivo assessment of mucoadhesive nanoparticles containing fluconazole for the local treatment of oral candidiasis. AB - This study aimed to develop a suitable buccal mucoadhesive nanoparticle (NP) formulation containing fluconazole for the local treatment of oral candidiasis. The suitability of the prepared formulations was assessed by means of particle size (PS), polydispersity index, and zeta potential measurements, morphology analysis, mucoadhesion studies, drug entrapment efficiency (EE), in vitro drug release, and stability studies. Based on the optimum NP formulation, ex vivo drug diffusion and in vitro cytotoxicity studies were performed. Besides, evaluation of the antifungal effect of the optimum formulation was evaluated using agar diffusion method, fungicidal activity-related in vitro release study, and time dependent fungicidal activity. The effect of the optimum NP formulation on the healing of oral candidiasis was investigated in an animal model, which was employed for the first time in this study. The zeta potential, mucoadhesion, and in vitro drug release studies of various NP formulations revealed that chitosan coated NP formulation containing EUDRAGIT((r)) RS 2.5% had superior properties than other formulations. Concerning the stability study of the selected formulation, the formulation was found to be stable for 6 months. During the ex vivo drug diffusion study, no drug was found in receptor phase, and this is an indication of local effect. The in vitro antifungal activity studies showed the in vitro efficacy of the NP against Candida albicans for an extended period. Also, the formulation had no cytotoxic effect at the tested concentration. For the in vivo experiments, infected rabbits were successfully treated with local administration of the optimum NP formulation once a day. This study has shown that the mucoadhesive NP formulation containing fluconazole is a promising candidate with once-a-day application for the local treatment of oral candidiasis. PMID- 27358562 TI - Impairments of spatial learning and memory following intrahippocampal injection in rats of 3-mercaptopropionic acid-modified CdTe quantum dots and molecular mechanisms. AB - With the rapid development of nanotechnology, quantum dots (QDs) as advanced nanotechnology products have been widely used in neuroscience, including basic neurological studies and diagnosis or therapy for neurological disorders, due to their superior optical properties. In recent years, there has been intense concern regarding the toxicity of QDs, with a growing number of studies. However, knowledge of neurotoxic consequences of QDs applied in living organisms is lagging behind their development, even if several studies have attempted to evaluate the toxicity of QDs on neural cells. The aim of this study was to evaluate the adverse effects of intrahippocampal injection in rats of 3 mercaptopropionic acid (MPA)-modified CdTe QDs and underlying mechanisms. First of all, we observed impairments in learning efficiency and spatial memory in the MPA-modified CdTe QD-treated rats by using open-field and Y-maze tests, which could be attributed to pathological changes and disruption of ultrastructure of neurons and synapses in the hippocampus. In order to find the mechanisms causing these effects, transcriptome sequencing (RNA-seq), an advanced technology, was used to gain the potentially molecular targets of MPA-modified CdTe QDs. According to ample data from RNA-seq, we chose the signaling pathways of PI3K-Akt and MPAK-ERK to do a thorough investigation, because they play important roles in synaptic plasticity, long-term potentiation, and spatial memory. The data demonstrated that phosphorylated Akt (p-Akt), p-ERK1/2, and c-FOS signal transductions in the hippocampus of rats were involved in the mechanism underlying spatial learning and memory impairments caused by 3.5 nm MPA-modified CdTe QDs. PMID- 27358563 TI - Symbiosis theory-directed green synthesis of silver nanoparticles and their application in infected wound healing. AB - In this study, silver nanoparticles (AgNPs) were synthesized for the first time using an antibacterial endophytic fungus of Chinese medicinal herb Orchidantha chinensis, which has anti-inflammatory and antimicrobial activities. The AgNPs were analyzed by various characterization techniques to reveal their morphology, chemical composition, and stability. Also, the relationship between Chinese medicinal herbs, endophytic fungi, and the property of AgNPs was investigated for the first time. Interestingly, an experiment performed in this study revealed the proteins produced by the endophytic fungus to be capped on the nanoparticles, which led to an increase in the stability of spherical and polydispersed AgNPs with low aggregation for over 6 months. More importantly, further study demonstrated that the AgNPs possessed superior antibacterial activity and effectively promoted wound healing. Altogether, the biosynthesis of active AgNPs using the endophytic fungus from Chinese medicinal herb based on the symbiosis theory is simple, eco-friendly, and promising. PMID- 27358564 TI - Biocompatible nanocarriers that respond to oxidative environments via interactions between chitosan and multiple metal ions. AB - Hydrogen peroxide (H2O2) functions as an early damage signal contributing to the oxidative stress response and can act as a trigger in smart oxidation-responsive drug delivery systems that are currently in development. Current H2O2-triggered oxidation-responsive polymeric systems are usually derived from chemical synthesis and rarely include natural polymers. Herein, we report two series of nanoparticle (NP) complexes prepared with the biopolymer chitosan (CS) and four different metal ions (Cu(2+), Ca(2+), Zn(2+), and Fe(3+)), defined as CSNPs-metal complexes (Series 1) and CS-metal complexes NPs (Series 2), which responded to oxidation by dissolving upon H2O2 exposure. Experiments examining Nile red release and H2O2-triggered degradation confirmed that both series of complexes showed better sensitivity to oxidation than the CSNPs alone. Furthermore, preliminary cytotoxicity and histological observations indicated that the two series exhibited little or no cytotoxicity and generated a mild inflammatory response. Our work provides a novel and promising strategy for developing NPs for use as intelligent oxidation-responsive systems. PMID- 27358565 TI - Receptor-targeted, drug-loaded, functionalized graphene oxides for chemotherapy and photothermal therapy. AB - Cancer is one of the leading causes of death worldwide. Although different chemotherapeutic agents have been developed to treat cancers, their use can be limited by low cellular uptake, drug resistance, and side effects. Hence, targeted drug delivery systems are continually being developed in order to improve the efficacy of chemotherapeutic agents. The main aim of this study was to prepare folic acid (FA)-conjugated polyvinyl pyrrolidone-functionalized graphene oxides (GO) (FA-GO) for targeted delivery of sorafenib (SF). GO were prepared using a modified Hummer's method and subsequently altered to prepare FA GO and SF-loaded FA-GO (FA-GO/SF). Characterization of GO derivatives was done using ultraviolet/visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, atomic force microscopy, zeta potential measurements, and determination of in vitro drug release. Hemolytic toxicity, in vitro cytotoxicity, cellular uptake, and apoptotic effects of FA-GO/SF were also investigated. The results revealed that GO was successfully synthesized and that further transformation to FA-GO improved the stability and SF drug-loading capacity. In addition, the enhanced SF release under acidic conditions suggested possible benefits for cancer treatment. Conjugation of FA within the FA-GO/SF delivery system enabled targeted delivery of SF to cancer cells expressing high levels of FA receptors, thus increasing the cellular uptake and apoptotic effects of SF. Furthermore, the photothermal effect achieved by exposure of GO to near infrared irradiation enhanced the anticancer effects of FA-GO/SF. Taken together, FA-GO/SF is a potential carrier for targeted delivery of chemotherapeutic agents in cancer. PMID- 27358566 TI - Volumetric brain abnormalities in polysubstance use disorder patients. AB - AIM: Polysubstance users represent the largest group of patients seeking treatment at addiction and rehabilitation clinics in Turkey. There is little knowledge about the structural brain abnormalities seen in polysubstance users. This study was conducted to examine the structural brain differences between polysubstance use disorder patients and healthy control subjects using voxel based morphometry. METHODS: Forty-six male polysubstance use disorder patients in the early abstinence period and 30 healthy male controls underwent structural magnetic resonance imaging scans. Voxel-based morphometry analysis was performed to examine gray matter (GM) abnormality differences. RESULTS: Polysubstance use disorder patients displayed significantly smaller GM volume in the thalamus, temporal pole, superior frontal gyrus, cerebellum, gyrus rectus, occipital lobe, anterior cingulate cortex, superior temporal gyrus, and postcentral gyrus. CONCLUSION: A widespread and smaller GM volume has been found at different regions of the frontal, temporal, occipital, and parietal lobes, cerebellum, and anterior cingulate cortex in polysubstance users. PMID- 27358567 TI - A benefit-risk assessment model for statins using multicriteria decision analysis based on a discrete choice experiment in Korean patients. AB - PURPOSE: The benefit-risk balance for drugs can alter post approval owing to additional data on efficacy or adverse events. This study developed a quantitative benefit-risk assessment (BRA) model for statins using multicriteria decision analysis with discrete choice experiments and compared a recent BRA with that at the time of approval. PATIENTS AND METHODS: Following a systematic review of the literature, the benefit criteria within the statin BRA model were defined as a reduction in the plasma low-density lipoprotein cholesterol level and a reduction in myocardial infarction incidence; the risk criteria were hepatotoxicity (Liv) and fatal rhabdomyolysis (Rha). The scores for these criteria were estimated using mixed treatment comparison methods. Weighting was calculated from a discrete choice experiment involving 203 Korean patients. The scores and weights were integrated to produce an overall value representing the benefit-risk balance, and sensitivity analyses were conducted. RESULTS: In this BRA model, low-density lipoprotein (relative importance [RI]: 37.50%) was found to be a more important benefit criterion than myocardial infarction (RI: 35.43%), and Liv (RI: 16.28%) was a more important risk criterion than Rha (RI: 10.79%). Patients preferred atorvastatin, and the preference ranking of cerivastatin and simvastatin was switched post approval because of the emergence of additional risk information related to cerivastatin. CONCLUSION: A quantitative statin BRA model confirmed that the preference ranking of statins changed post approval because of the identification of additional benefits or risks. PMID- 27358568 TI - Effectiveness of a thoracic multidisciplinary clinic in the treatment of stage III non-small-cell lung cancer. AB - INTRODUCTION: The Institute of Medicine, the American Society of Clinical Oncology, and the European Society of Medical Oncology promote a multidisciplinary approach for the treatment of cancer. Stage III non-small-cell lung cancer (NSCLC) represents a heterogeneous group of diseases necessitating coordination of care among medical, radiation, and surgical oncology. The optimal care of stage III NSCLC underscores the need for a multidisciplinary approach. METHODS: From tumor registry data, we identified all cases of stage III NSCLC seen at Lehigh Valley Health Network between March 2010 and March 2013. The care received by patients when seen in the thoracic multidisciplinary clinic (MDC) was compared with the care received when not seen in the thoracic MDC. RESULTS: All patients seen in the MDC, compared to <50% of patients seen outside the MDC, were evaluated by more than one physician prior to beginning the treatment. Time to initiate treatment was shorter in MDC patients than in non-MDC patients. Patients seen in the MDC had a greater concordance with clinical pathways. A greater percentage of patients seen in the thoracic MDC had pathologic staging of their mediastinum. Patients seen in the MDC were more likely to receive all of their care at Lehigh Valley Health Network. CONCLUSION: Multidisciplinary care is essential in the treatment of patients with stage III NSCLC. Greater utilization of MDCs for this complex group of patients will result in more efficient coordination of care, pretreatment evaluation, and therapy, which in turn should translate to improve patients' outcomes. PMID- 27358569 TI - Optimal management of genital herpes: current perspectives. AB - As one of the most common sexually transmitted diseases, genital herpes is a global medical problem with significant physical and psychological morbidity. Genital herpes is caused by herpes simplex virus type 1 or type 2 and can manifest as primary and/or recurrent infection. This manuscript provides an overview about the fundamental knowledge on the virus, its epidemiology, and infection. Furthermore, the current possibilities of antiviral therapeutic interventions and laboratory diagnosis of genital herpes as well as the present situation and perspectives for the treatment by novel antivirals and prevention of disease by vaccination are presented. Since the medical management of patients with genital herpes simplex virus infection is often unsatisfactory, this review aims at all physicians and health professionals who are involved in the care of patients with genital herpes. The information provided would help to improve the counseling of affected patients and to optimize the diagnosis, treatment, and prevention of this particular disease. PMID- 27358570 TI - Scaling up health knowledge at European level requires sharing integrated data: an approach for collection of database specification. AB - Computerized health care databases have been widely described as an excellent opportunity for research. The availability of "big data" has brought about a wave of innovation in projects when conducting health services research. Most of the available secondary data sources are restricted to the geographical scope of a given country and present heterogeneous structure and content. Under the umbrella of the European Innovation Partnership on Active and Healthy Ageing, collaborative work conducted by the partners of the group on "adherence to prescription and medical plans" identified the use of observational and large population databases to monitor medication-taking behavior in the elderly. This article describes the methodology used to gather the information from available databases among the Adherence Action Group partners with the aim of improving data sharing on a European level. A total of six databases belonging to three different European countries (Spain, Republic of Ireland, and Italy) were included in the analysis. Preliminary results suggest that there are some similarities. However, these results should be applied in different contexts and European countries, supporting the idea that large European studies should be designed in order to get the most of already available databases. PMID- 27358571 TI - A comparison of EuroQol 5-Dimension health-related utilities using Italian, UK, and US preference weights in a patient sample. AB - Weights associated with the EuroQol 5-Dimension 3-Level (EQ-5D-3L) instrument represent preferences for health states elicited from general population's samples. Weights have not been calculated for every country; however, empirical research shows that cross-country differences exist. This empirical study aims at investigating the impact of recently developed Italian weights in comparison with UK and US scores on health-related utility calculation using a sample of patients with Crohn's disease. The study is based on a survey on health-related quality of life in patients (n=552) affected by active Crohn's disease conducted in Italy from 2012 to 2013. Utilities computed through the Italian algorithm (mean: 0.76; SD: 0.20; median: 0.81) are generally higher than US (mean: 0.69; SD: 0.22; median: 0.77) and UK (mean: 0.57; SD: 0.32; median: 0.69) utilities, except for extremely severe health states where US values outweigh the Italian ones. UK preference weights generate the highest number of negative results. All the three value distributions are left-skewed due to very low scores associated with the most serious health states (ie, three or four levels equal to 3). As expected, despite the tariff set considered, more severe disease (Harvey Bradshaw Index >16) reduces the mean conditional EQ-5D-3L index (P<0.0001). Kendall's rank correlation between EQ Visual Analog Scale score and EQ-5D-3L index is positive (P<0.0001), even though patients tend to value their health-related quality of life more when responding to EQ-5D-3L questions than on EQ Visual Analog Scale. Regardless of the tariff set considered, ordinary least-square results highlight that more severe disease (Harvey Bradshaw Index >16) reduces the mean conditional EQ-5D-3L index (P<0.0001). Results reveal remarkable differences among the three national tariff sets and especially when severe health states occur, suggesting the need for country-specific preference weights when evaluating utilities, which can be problematic since they have not been calculated for every country yet. PMID- 27358572 TI - CAF1-knockout mice are more susceptive to lipopolysaccharide-induced acute lung injury. AB - The carbon catabolite repressor protein 4 (CCR4)-negative on TATA (NOT) complex includes multiple subunits and is conserved in the eukaryotic cells. The CCR4-NOT complex can regulate gene expression at different levels. Two subunits of the CCR4-NOT complex, CCR4 and CCR4-associated factor 1 (CAF1), possess deadenylase activity. In yeast, the deadenylase activity is mainly provided by the CCR4 subunit; however, the deadenylase activity is provided by both CCR4 and CAF1 in other eukaryotes. A previous study reported that CAF1 but not CCR4 is required for the decay of a reporter mRNA with AU-rich elements. Our previous study showed that CAF1 is involved in the regulation of intercellular adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8) expression. Both ICAM-1 and IL-8 play crucial roles in acute lung injury. In the present study, we examined the effects of CAF1 deficiency on IL-8 and ICAM-1 expression and acute lung injury in mice. Here we showed that there were no differences between the wild-type and CAF1-knockout mice on phenotypes. The lung histology and protein and mRNA levels of IL-8 and ICAM-1 in unstimulated wild-type mice were comparable to those in unstimulated CAF1-knockout mice. However, lipopolysaccharide stimulation led to more severe lung histological injury and greatly higher IL-8 and ICAM-1 expression in CAF1 knockout mice compared to the wild-type mice. These results, together with our previous study, suggest that CAF1 is involved in the regulation of lipopolysaccharide-stimulated IL-8 and ICAM-1 expression in vivo and affects the progression of acute lung injury. PMID- 27358573 TI - Thoracic epidural analgesia to control malignant pain until viability in a pregnant patient. AB - Management of nonobstetric pain in the pregnant patient presents unique challenges related to transplacental fetal exposure to opioids and the subsequent risk of neonatal withdrawal syndrome. We present the case of a pregnant patient suffering from the pain of a progressively enlarging thoracoabdominal sarcoma. Epidural analgesia (using local anesthetics with minimal opioid) was utilized over a span of weeks to manage oncologic pain, limiting fetal opioid exposure and culminating in the birth of a healthy infant. While nonobstetric abdominal pain during pregnancy is not that uncommon, neoplastic abdominal pain does appear to be rare. Combined local anesthetic and opioid continuous epidural infusion should be considered a viable option in the pain management approach to obstetric patients with nonobstetric pain associated with malignancy. PMID- 27358574 TI - Safety and efficacy of nurse-controlled analgesia in patients less than 1 year of age. AB - BACKGROUND: The management of acute pain presents unique challenges in the younger pediatric population. Although patient-controlled devices are frequently used in patients >=6 years of age, alternative modes of analgesic delivery are needed in infants. OBJECTIVE: To examine the safety and efficacy of nurse controlled analgesia (NCA) in neonates less than 1 year of age. METHODS: Data from patients <1 year of age receiving NCA as ordered by the Acute Pain Service at our institution were collected over a 5-year period and reviewed retrospectively. The primary outcomes were activation of the institution's Rapid Response Team (RRT) or Code Blue, signifying severe adverse events. Pain score after NCA initiation was a secondary outcome. RESULTS: Among 338 girls and 431 boys, the most common opioid used for NCA was fentanyl, followed by morphine and hydromorphone. There were 39 (5%) cases involving RRT or Code Blue activation, of which only one (Code Blue) was activated due to a complication of NCA (apnea). Multivariable logistic regression demonstrated morphine NCA to be associated with greater odds of RRT activation (OR=3.29, 95% CI=1.35, 8.03, P=0.009) compared to fentanyl NCA. There were no statistically significant differences in pain scores after NCA initiation across NCA agents. CONCLUSION: NCA is safe in neonates and infants, with comparable efficacy demonstrated for the three agents used. The elevated incidence of RRT activation in patients receiving morphine suggests caution in its use and consideration of alternative agents in this population. PMID- 27358575 TI - Does a research group increase impact on the scientific community or general public discussion? Alternative metric-based evaluation. AB - In this study, we investigated the impact of scientific publications of the Italian SIMPAR (Study In Multidisciplinary PAin Research) group by using altmetrics, defined as nontraditional metrics constituting an alternative to more traditional citation-impact metrics, such as impact factor and H-index. By correlating traditional and alternative metrics, we attempted to verify whether publications by the SIMPAR group collectively had more impact than those performed by its individual members, either in solo publications or in publications coauthored by non-SIMPAR group investigators (which for the purpose of this study we will refer to as "individual publications"). For all the 12 members of the group analyzed (pain therapists, biologists, and pharmacologists), we created Open Researcher and Contributor ID and Impact Story accounts, and synchronized these data. Manually, we calculated the level metrics for each article by dividing the data obtained from the research community by those obtained from the public community. We analyzed 759 articles, 18 of which were published by the SIMPAR group. Altmetrics demonstrated that SIMPAR group publications were more likely to be saved (77.8% vs 45.9%), discussed (61.1% vs 1.1%, P<0.0001), and publicly viewed (11.1% vs 1.3%, P=0.05) than individual publications. These results support the importance of multidisciplinary research groups in the impact of scientific literature; the interaction and synergy among the research participants allowed the obtainment of high impact-literature in the field of personalized pain medicine. Finally, our findings demonstrate the potential of altmetrics in estimating the value of the research products of a group. PMID- 27358576 TI - The pain drawing as an instrument for identifying cervical spine nerve involvement in chronic whiplash-associated disorders. AB - OBJECTIVE: The aim of the study was to investigate the psychometric properties of a standardized assessment of pain drawing with regard to clinical signs of cervical spine nerve root involvement. DESIGN: This cross-sectional study included data collected in a randomized controlled study. PATIENTS: Two hundred and sixteen patients with chronic (>=6 months) whiplash-associated disorders, grade 2 or 3, were included in this study. METHODS: The validity, sensitivity, and specificity of a standardized pain drawing assessment for determining nerve root involvement were analyzed, compared to the clinical assessment. In addition, we analyzed the interrater reliability with 50 pain drawings. RESULTS: Agreement was poor between the standardized pain drawing assessment and the clinical assessment (kappa =0.11, 95% CI: -0.03 to 0.20). Sensitivity was high (93%), but specificity was low (19%). Interrater reliability was good (kappa =0.64, 95% CI: 0.53 to 0.76). CONCLUSION: The standardized pain drawing assessment of nerve root involvement in chronic whiplash-associated disorders was not in agreement with the clinical assessment. Further research is warranted to optimize the utilization of a pain/discomfort drawing as a supportive instrument for identifying nerve involvement in cervical spinal injuries. PMID- 27358577 TI - The Use of Female Sex Workers Among Men in Nepal: Prevalence, STIs/HIV-Related Risk Behaviors, and Gender Ideology. AB - Heterosexual sex involving female sex workers (FSWs) is widely documented for its role in facilitating the spread of sexually transmitted infections (STIs)/HIV. Critical to such studies, and increasingly considered essential to HIV prevention efforts, is the gender constructs and power dynamics within relationships. However, little efforts have been made, which focus on male clients of FSWs, particularly on the relationship between gender ideologies and men's sexual contact with FSWs, within the Nepali context. The present study aims to fill this critical gap by assessing the prevalence of use of FSWs and its association with STIs/HIV-related risk behaviors and gender ideologies among Nepali men. We used data from the nationally representative Nepal Demographic Health Survey (NDHS) 2011. For the purpose of analyses, we included a sample of 4,121 men, aged 15-49 years. During data analyses, we used multivariate logistic regression models, adjusted for the following variables: age, region, residence, religion, educational level, wealth index, employment status, and cigarette smoking status. Of the total sample, approximately 5% reported the use of FSWs in their lifetime. In regression models, men who had sex with FSWs were more likely to report a history of STIs [adjusted odds ratio (aOR): 3.03; 95% confidence interval (CI): 1.69-5.43; P < 0.001], not using condom all the time (aOR: 1.31; 95% CI: 1.05 2.12; P = 0.010), more than one sexual partner (aOR: 3.75; 95% CI: 2.18-5.23; P < 0.001), and have had early sexual debut (aOR: 2.60; 95% CI: 1.85-3.67; P < 0.001). Respondents reporting the endorsement of violence against wives (aOR: 1.65; 95% CI: 1.01-2.84; P = 0.04) and male sexual entitlement (aOR: 1.63; 95% CI: 1.21-2.32; P = 0.001) were significantly more likely to report sexual contact with FSWs. Our findings highlight the need to develop and implement specifically tailored interventions toward male clients of FSWs, with a particular emphasis on promoting equitable gender roles and beliefs. PMID- 27358579 TI - Non-cell-autonomous Neurotoxicity of alpha-synuclein Through Microglial Toll-like Receptor 2. AB - Synucleinopathies are a collection of neurological diseases that are characterized by deposition of alpha-synuclein aggregates in neurons and glia. These diseases include Parkinson's disease (PD), dementia with Lewy bodies, and multiple system atrophy. Although it has been increasingly clear that alpha synuclein is implicated in the pathogenesis of PD and other synucleinopathies, the precise mechanism underlying the disease process remains to be unraveled. The past studies on how alpha-synuclein exerts pathogenic actions have focused on its direct, cell-autonomous neurotoxic effects. However, recent findings suggested that there might be indirect, non-cell-autonomous pathways, perhaps through the changes in glial cells, for the pathogenic actions of this protein. Here, we present evidence that alpha-synuclein can cause neurodegeneration through a non cell-autonomous manner. We show that alpha-synuclein can be secreted from neurons and induces inflammatory responses in microglia, which in turn secreted neurotoxic agents into the media causing neurodegeneration. The neurotoxic response of microglia was mediated by activation of toll-like receptor 2 (TLR2), a receptor for neuron-derived alpha-synuclein. This work suggests that TLR2 is the key molecule that mediates non-cell-autonomous neurotoxic effects of alpha synuclein, hence a candidate for the therapeutic target. PMID- 27358578 TI - Adult Neurogenesis and Gliogenesis: Possible Mechanisms for Neurorestoration. AB - The subgranular zone (SGZ) and subventricular zone (SVZ) are developmental remnants of the germinal regions of the brain, hence they retain the ability to generate neuronal progenitor cells in adult life. Neurogenesis in adult brain has an adaptive function because newly produced neurons can integrate into and modify existing neuronal circuits. In contrast to the SGZ and SVZ, other brain regions have a lower capacity to produce new neurons, and this usually occurs via parenchymal and periventricular cell genesis. Compared to neurogenesis, gliogenesis occurs more prevalently in the adult mammalian brain. Under certain circumstances, interaction occurs between neurogenesis and gliogenesis, facilitating glial cells to transform into neuronal lineage. Therefore, modulating the balance between neurogenesis and gliogenesis may present a new perspective for neurorestoration, especially in diseases associated with altered neurogenesis and/or gliogenesis, cell loss, or disturbed homeostasis of cellular constitution. The present review discusses important neuroanatomical features of adult neurogenesis and gliogenesis, aiming to explore how these processes could be modulated toward functional repair of the adult brain. PMID- 27358580 TI - Neuronal Expression and Cell-Type-Specific Gene-Silencing of Best1 in Thalamic Reticular Nucleus Neurons Using pSico-Red System. AB - Assessing the cell-type expression pattern of a certain gene can be achieved by using cell-type-specific gene manipulation. Recently, cre-recombinase-dependent gene-silencing tool, pSico has become popular in neuroscientific research. However, pSico has a critical limitation that gene-silenced cell cannot be identified by fluorescence, due to an excision of the reporter gene for green fluorescence protein (GFP). To overcome this limitation, we newly developed pSico Red, with mCherry gene as a reporter outside two loxP sites, so that red mCherry signal is detected in all transfected cells. When a cell expresses cre, GFP is excised and shRNA is enabled, resulting in disappearance of GFP. This feature of pSico-Red provides not only cell-type-specific gene-silencing but also identification of cre expressing cells. Using this system, we demonstrated for the first time the neuronal expression of the Bestrophin-1 (Best1) in thalamic reticular nucleus (TRN) and TRN-neuron-specific gene-silencing of Best1. We combined adeno-associated virus (AAV) carrying Best1-shRNA in pSico-Red vector and transgenic mouse expressing cre under the promoter of distal-less homeobox 5/6 (DLX5/6), a marker for inhibitory neurons. Firstly, we found that almost all of inhibitory neurons in TRN express Best1 by immunohistochemistry. Using pSico Red virus, we found that 80% of infected TRN neurons were DLX5/6-cre positive but parvalbumin negative. Finally, we found that Best1 in DLX5/6-cre positive neurons were significantly reduced by Best1-shRNA. Our study demonstrates that TRN neurons strongly express Best1 and that pSico-Red is a valuable tool for cell type-specific gene manipulation and identification of specific cell population. PMID- 27358581 TI - Cerebral Hemodynamics and Vascular Reactivity in Mild and Severe Ischemic Rodent Middle Cerebral Artery Occlusion Stroke Models. AB - Ischemia can cause decreased cerebral neurovascular coupling, leading to a failure in the autoregulation of cerebral blood flow. This study aims to investigate the effect of varying degrees of ischemia on cerebral hemodynamic reactivity using in vivo real-time optical imaging. We utilized direct cortical stimulation to elicit hyper-excitable neuronal activation, which leads to induced hemodynamic changes in both the normal and middle cerebral artery occlusion (MCAO) ischemic stroke groups. Hemodynamic measurements from optical imaging accurately predict the severity of occlusion in mild and severe MCAO animals. There is neither an increase in cerebral blood volume nor in vessel reactivity in the ipsilateral hemisphere (I.H) of animals with severe MCAO. The pial artery in the contralateral hemisphere (C.H) of the severe MCAO group reacted more slowly than both hemispheres in the normal and mild MCAO groups. In addition, the arterial reactivity of the I.H in the mild MCAO animals was faster than the normal animals. Furthermore, artery reactivity is tightly correlated with histological and behavioral results in the MCAO ischemic group. Thus, in vivo optical imaging may offer a simple and useful tool to assess the degree of ischemia and to understand how cerebral hemodynamics and vascular reactivity are affected by ischemia. PMID- 27358582 TI - Toxocara canis-Associated Myelitis with Eosinophilic Pneumonia. AB - The existence of Toxocara canis-specific antibodies has recently been reported in patients with atopic myelitis. Here, we report the case of a 35-year-old male patient admitted with a chief complaint of right lower limb hypoesthesia lasting for a month. The patient was diagnosed with eosinophilic pneumonia 3 months ago, and a spine MRI revealed the presence of myelitis in the cervicothoracic cord. After confirming the presence of hyper-IgE-emia and Toxocara canis antibodies, the patient was treated with steroids and albendazole treatment, which improved his symptoms. To our knowledge, this is the first case of Toxocara canis associated myelitis with eosinophilic pneumonia. PMID- 27358583 TI - Bilateral Adduction Palsy in a Patient with Myotonic Dystrophy Type 1. AB - Myotonic dystrophy type 1 (DM1) is caused by CTG repeat expansion in the DMPK gene in chromosome 19q13.3. External ophthalmoplegia is a rare manifestation in DM1. We report a DM1 patient confirmed by the presence of 650 CTG triplet expansions in the DMPK gene and had limitation of adduction gaze bilaterally. Brain MRI showed bilateral medial rectus muscles atrophy. Our patient provides additional evidence of ocular motor muscle involvement in DM1. PMID- 27358585 TI - In situ production of titanium dioxide nanoparticles in molten salt phase for thermal energy storage and heat-transfer fluid applications. AB - In this study, TiO2 nanoparticles (average particle size 16 nm) were successfully produced in molten salt phase and were showed to significantly enhance the specific heat capacity of a binary eutectic mixture of sodium and potassium nitrate (60/40) by 5.4 % at 390 degrees C and 7.5 % at 445 degrees C for 3.0 wt% of precursors used. The objective of this research was to develop a cost effective alternate method of production which is potentially scalable, as current techniques utilized are not economically viable for large quantities. Enhancing the specific heat capacity of molten salt would promote more competitive pricing for electricity production by concentrating solar power plant. Here, a simple precursor (TiOSO4) was added to a binary eutectic mixture of potassium and sodium nitrate, heated to 450 degrees C, and cooled to witness the production of nanoparticles. PMID- 27358584 TI - Urothelial carcinoma management in elderly or unfit patients. PMID- 27358587 TI - Chemoradiotherapy for locally advanced pancreatic cancer patients: is it still an open question? AB - Operable pancreatic cancer is characterized by a high risk of recurrence. Efforts are made to incorporate new therapies. Throughout the world there is a lack of uniform recommendations concerning the adjuvant treatment of pancreatic cancer patients, due to confusing evidence-based data. The patients recruited to clinical trials differ from the population of patients treated in everyday practice. These differences have an influence on tolerance of treatment, toxicity and results of therapy. The decision on administration of adjuvant treatment is made individually and differs from center to center. A review of the literature concerning both results and tolerance of postoperative chemoradiotherapy of pancreatic cancer patients is presented. PMID- 27358586 TI - The role of preoperative systemic treatment in patients with breast cancer. AB - The goal of preoperative pharmacotherapy in patients with breast cancer is to enable breast conserving surgery in stage T3N0-1M0 or radical mastectomy in patients with primary inoperative tumors (T1-4N0-3M0). The choice of optimal treatment should be based not only on risk factors resulting from the stage but also on predicted cancer responsiveness to the treatment. The breast cancer subtypes defined by immunohistochemical profile (expression of ER, PR, HER2 and Ki67) are characterized by different responsiveness to therapy. Complete response confirmed by histopathological evaluation after neoadjuvant chemotherapy is a positive prognostic factor in some breast cancer subtypes. This marker is not of value in postmenopausal patients with ER/PR+ HER2- tumors, who are candidates for neoadjuvant hormone therapy. These patients have a good prognosis if in a histopathological report after surgery there are features such as pT1, pN0, Ki67 < 3%, and ER Allred score >= 3. The goal of the paper is to present current knowledge about preoperative pharmacotherapy of breast cancer. PMID- 27358588 TI - New perspectives in glioblastoma antiangiogenic therapy. AB - Glioblastoma (GB) is highly vascularised tumour, known to exhibit enhanced infiltrative potential. One of the characteristics of glioblastoma is microvascular proliferation surrounding necrotic areas, as a response to a hypoxic environment, which in turn increases the expression of angiogenic factors and their signalling pathways (RAS/RAF/ERK/MAPK pathway, PI3K/Akt signalling pathway and WTN signalling cascade). Currently, a small number of anti-angiogenic drugs, extending glioblastoma patients survival, are available for clinical use. Most medications are ineffective in clinical therapy of glioblastoma due to acquired malignant cells or intrinsic resistance, angiogenic receptors cross activation and redundant intracellular signalling, or the inability of the drug to cross the blood-brain barrier and to reach its target in vivo. Researchers have also observed that GB tumours are different in many aspects, even when they derive from the same tissue, which is the reason for personalised therapy. An understanding of the molecular mechanisms regulating glioblastoma angiogenesis and invasion may be important in the future development of curative therapeutic approaches for the treatment of this devastating disease. PMID- 27358589 TI - Acupuncture: could it become everyday practice in oncology? AB - Acupuncture is a complementary and alternative medical treatment (CAM) which is increasingly used in the care of cancer patients. Traditionally derived from Chinese medicine, nowadays it is becoming a part of evidence-based oncology. The use of acupuncture in these patients has been recommended by the American Cancer Society (ACS) for the treatment of side effects associated with conventional cancer therapy and cancer-related ailments. A growing body of evidence supports the use of acupuncture in the treatment of cancer-induced pain and chemotherapy related nausea and vomiting. Also other indications, such as xerostomia, fatigue, hot flashes, anxiety and peripheral neuropathy, are being constantly evaluated. This article summarizes the most important discoveries related to the possible usefulness of this method in contemporary oncology. Emphasis is placed on the results of randomized controlled trials with an adequate level of evidence. However, explanation of the mechanisms responsible for these effects requires confirmation in further studies with an adequate level of evidence. In future, acupuncture may become an interesting and valuable addition to conventional medicine. PMID- 27358590 TI - k-RAS mutations in non-small cell lung cancer patients treated with TKIs among smokers and non-smokers: a meta-analysis. AB - AIM OF THE STUDY: Recent studies have suggested that k-RAS mutations are related to the response to epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitions (TKIs) in advanced non-small cell lung cancer (NSCLC) treatment. The aim of this meta-analysis was to assess the relationship between smoking history and k-RAS mutations in NSCLC treated with TKIs. MATERIAL AND METHODS: We searched MEDLINE and Web of Science up to 15 March 2014. The pooled relative risk (RR) was estimated by using fixed effect model or random effect model, according to heterogeneity between studies. We also carried out power analyses. RESULTS: We identified 12 studies with 1193 patients, including 196 patients (16.4%) with k RAS mutations. The pooled k-RAS mutations incidence was 22.8% (174/764) in patients with smoke expose vs. 5.4% (23/429) in those with no smoke exposure. The pooled RR was 2.991 (95% CI: 1.884-4.746; Z = 4.65, p = 0.000). No publication bias was found (Begg's test: z = 1.09, p = 0.274 and Egger's test: t = 1.38, p = 0.201). In subgroup analyses, the pooled RR was 3.336 (95% CI: 1.925-5.779; Z = 4.30, p = 0.000) in the Caucasian subgroup, while in the Asian subgroup the pooled RR was 2.093 (95% CI: 0.909-4.822; Z = 1.73, p = 0.083), but the sample size was underpowered (0.465). CONCLUSIONS: The current meta-analysis found that smoking was related to increased incidence of k-RAS mutations in non-small cell lung cancer treated with TKIs. This may be further evidence that smoking will lead to a worse prognosis in NSCLC patients treated with TKIs. PMID- 27358591 TI - Expression of insulin-like growth factor family genes in clear cell renal cell carcinoma. AB - AIM OF THE STUDY: Despite significant progress in the pathology of clear cell renal cell carcinoma (ccRCC), diagnostic and predictive factors of major importance have not been discovered. Some hopes are associated with insulin-like growth factors. The aim of the study was to compare the expression of genes for insulin-like growth factor family in tumours and in tissue of kidneys without cancer. MATERIAL AND METHODS: Fifty-two patients years with clear cell renal cell cancer were qualified to the study group; patients nephrectomised because of hydronephrosis were included in the control group. Expression of genes were evaluated by RT-PCR. RESULTS: Expression of IGFR-1 gene in tumour accounts for about 60% of cases. The incidence is higher than in corresponding adjacent non cancerous kidney tissues and higher (but with no statistical significance) than in kidney without cancer. Expression of IGFR-2 gene in tumours has not been established. The incidence of the expression in corresponding adjacent non cancerous kidney tissues is small. Expression of this gene has been present in all specimens from kidneys without cancer. Expression of IGFBP-3 gene ascertained in all (except four) cases of ccRCC and in the majority of clippings from adjacent tissue. It was not found in kidneys from the control group. IGF-1, IGF 2, and IGFR-1 mRNA copy numbers in ccRCC were higher than in the material from the control group. PMID- 27358592 TI - In vivo skin dose measurement in breast conformal radiotherapy. AB - AIM OF THE STUDY: Accurate skin dose assessment is necessary during breast radiotherapy to assure that the skin dose is below the tolerance level and is sufficient to prevent tumour recurrence. The aim of the current study is to measure the skin dose and to evaluate the geometrical/anatomical parameters that affect it. MATERIAL AND METHODS: Forty patients were simulated by TIGRT treatment planning system and treated with two tangential fields of 6 MV photon beam. Wedge filters were used to homogenise dose distribution for 11 patients. Skin dose was measured by thermoluminescent dosimeters (TLD-100) and the effects of beam incident angle, thickness of irradiated region, and beam entry separation on the skin dose were analysed. RESULTS: Average skin dose in treatment course of 50 Gy to the clinical target volume (CTV) was 36.65 Gy. The corresponding dose values for patients who were treated with and without wedge filter were 35.65 and 37.20 Gy, respectively. It was determined that the beam angle affected the average skin dose while the thickness of the irradiated region and the beam entry separation did not affect dose. Since the skin dose measured in this study was lower than the amount required to prevent tumour recurrence, application of bolus material in part of the treatment course is suggested for post-mastectomy advanced breast radiotherapy. It is more important when wedge filters are applied to homogenize dose distribution. PMID- 27358594 TI - Prognostic relevance of sunitinib toxicities and comparison of continuous vs. intermittent sunitinib dosing schedule in metastatic renal cell cancer patients. AB - AIM OF THE STUDY: Sunitinib-related side effects may develop as a result of the pharmacokinetic pathway affects the of the drug. MATERIAL AND METHODS: Data on mRCC patients were obtained from the hospital archives. Outcomes of patients were evaluated in terms of related prognostic factors, sunitinib adverse events during the treatment, and two different sunitinib dosing schedules. RESULTS: Seventy patients diagnosed with mRCC and treated with sunitinib were analyzed for prognostic factors and survival rates. During the mean follow-up of 33.5 months, 38 (54%) patients were alive and 32 (46%) patients died. The median time of overall survival (OS) and progression-free survival (PFS) was 27 months (12-61) and 19 months (5-45), respectively. In univariate analysis, good prognostic risk group according to the Memorial Sloan-Kettering Cancer Center (MSKCC), hypothyroidism as sunitinib toxicity and patients on sunitinib treatment more than 1 year were favorable prognostic factors for OS. Leukopenia and fatigue as sunitinib toxicity were poor prognostic factors for OS. PFS and OS of the patients were not significantly different when we compared intermittent (4/2) vs. continuous treatment dosing schedules. CONCLUSIONS: As a result of this trial, having hypothyroidism as an adverse effect of sunitinib was a favorable prognostic factor for OS and PFS in mRCC patients. It was also found that 4/2 and continuous dosing schedules of sunitinib did not give rise to different outcomes in mRCC patients. PMID- 27358593 TI - Clinical outcomes and prognostic factors of adult's Ewing sarcoma family of tumors: single center experience. AB - AIM OF THE STUDY: Aim of the study was to investigate the demographics of Ewing sarcoma family of tumours (ESTF) patients, treatment alternatives, clinical outcomes, and prognostic factors for survival. MATERIAL AND METHODS: We retrospectively reviewed 39 patients with ESFT who were admitted to our institute between September 2008 and September 2012. RESULTS: The patients included 32 (82.1%) males and seven (17.9%) females of median age 24 (range, 18-66) years. Among the 27 patients with a primary osseous localization, 17 (43.5%) had a central axis localization. Fifteen patients (38.5%) had metastases at the time of diagnosis. Patients were followed up for a median period of 18 (range, 2-134) months. The median event-free survival (EFS) was 23 (range, 1-64) months, and the 1- and 4-year EFS were 60% and 48%, respectively. The median overall survival (OS) was 91 (range, 1-188) months, and the 1- and 4-year OS were 78% and 54%, respectively. Gender, age, primary tumor site, and local treatment modalities, either alone or in combination, did not have a significant effect on OS (p = 0.210, p = 0.617, p = 0.644, and p = 0.417, respectively). In contrast, osseous site of peripheral localization, limited stage, and metastasis to the bone significantly affected OS (p = 0.015, p < 0.001, and p = 0.042, respectively). CONCLUSIONS: ESFTs are aggressive tumors with a high rate of relapse and metastatic potential. Patients with peripheral bone involvement and limited stage had a good prognosis. Appropriate surgical resection, radiotherapy, and aggressive chemotherapy regimens are recommended. PMID- 27358595 TI - Evaluation of the effects of red blood cell distribution width on survival in lung cancer patients. AB - AIM OF THE STUDY: Data are available indicating that red blood cell distribution width (RDW) is higher in cancer patients compared to healthy individuals or benign events. In our study, we aimed to investigate the influence of different RDW levels on survival in lung cancer patients. MATERIAL AND METHODS: Clinical and laboratory data from 146 patients with lung cancer and 40 healthy subjects were retrospectively studied. RDW was recorded before the application of any treatment. Patients were categorised according to four different RDW cut-off values (median RDW, RDW determined by ROC curve analysis, the upper limit at the automatic blood count device, and RDW cut of value which used in previous studies). Kaplan-Meier survival analysis was used to examine the effect of RDW on survival for each cut-off level. RESULTS: The median age of patients was 56.5 years (range: 26-83 years). The difference in median RDW between patients and the control group was statistically significant (14.0 and 13.8, respectively, p = 0.04). There was no difference with regard to overall survival when patients with RDW >= 14.0 were compared to those with RDW < 14.0 (p = 0.70); however, overall survival was 3.0 months shorter in low values of its own group in each of the following cut-off values: >= 14.2 (p = 0.34), >= 14.5 (p = 0.25), >= 15 (p = 0.59), although no results were statistically significant. DISCUSSION: We consider that the difference between low and high RDW values according to certain cut-off values may reflect the statistics of larger studies although there is a statistically negative correlation between RDW level and survival. PMID- 27358596 TI - The effect of pre-emptive analgesia on the level of postoperative pain in women undergoing surgery for breast neoplasm. AB - AIM OF THE STUDY: Dynamic development of research on pain has resulted in the formulation of the concept of pre-emptive analgesia, which involves administration of analgesics before the first pain-producing stimulus appears. It is meant to prevent increased sensitivity to pain in the postoperative period. The aim of this study was to assess the possibilities of modifying the intensity of postoperative pain evaluated with the visual analogue scale (VAS) in patients after surgical treatment for breast neoplasm offered by pre-emptive analgesia. MATERIAL AND METHODS: The intensity of postoperative pain was measured immediately after the surgery as well as 6, 12, 18, and 24 hours later in 100 women who had undergone surgery for breast tumour. The correlation between experienced pain and the type of analgesic administered pre-emptively, including metamizole, tramadol, ketoprofen, and placebo was examined. The effect of other correlates such as the extensiveness of surgery, systolic and diastolic blood pressure, and heart rate on the level of experienced pain as well as the usefulness of physiological parameters for its assessment were also analysed. RESULTS: The conducted study demonstrated the effectiveness of tramadol (p = 0.004) and ketoprofen (p = 0.039) administered half an hour before the beginning of surgery, but there was no similar effect in the case of metamizole (p = 1.0). A positive correlation was observed between the level of experienced pain and blood pressure values (p < 0.001). Heart rate does not seem to be significantly linked with the intensity of experienced pain (p = 0.157). PMID- 27358597 TI - An evaluation study of the determinants of future perspective and global Quality of Life in Spanish long-term premenopausal early-stage breast cancer survivors. AB - AIM OF THE STUDY: Quality of life (QL) is important in premenopausal long-term breast cancer survivors. In this study we assessed QL and factors associated with future perspective and global QL in premenopausal early-stage long-term breast cancer survivors from Spain. MATERIAL AND METHODS: 243 premenopausal stage I-IIIA relapse-free breast cancer patients who had received surgery 5-20 years previously completed EORTC QLQ-C30 and QLQ-BR23 questionnaires once during follow up. Univariate and multivariate logistic regression analyses were performed. RESULTS: QL mean scores were high in most areas (> 80 in functioning; < 20 in symptoms). The main factors for future perspective were emotional and social functioning, fatigue, breast symptom, and body image. The main factors for global QL were fatigue, pain and physical functioning, and emotional and social functioning. The best logistic model to explain future perspective associated high emotional and social functioning and low breast symptoms with a lower risk of low future perspective (R(2) = 0.56). Higher scores in physical and emotional functioning and lower scores in fatigue were associated with a lower risk of low global QL (R(2) = 0.50). CONCLUSIONS: Psychological, social, and physical factors were found to be possible determinants of global QL and future perspective. QL in premenopausal early-stage long-term breast cancer survivors may benefit from multidisciplinary treatment. PMID- 27358598 TI - Anxiety and depression and cognitive coping strategies and health locus of control in patients with ovary and uterus cancer during anticancer therapy. AB - AIM OF THE STUDY: The crisis associated with cancer may contribute to the development of anxiety and depressive disorders. Contemporary psycho-oncology focuses on the psychological determinants of the cancer patients functioning to find which disease-coping strategies help the healing process, facilitate the establishment of a good therapeutic relationship and the process of adapting to difficult situations. Aim of the study was assess the psychological functioning of patients with cancer of reproductive organs in the cancer-treating process. The practical aim was to develop guidelines for psychological care dedicated to this group of patients. MATERIAL AND METHODS: The study was conducted in the Reproductive Organs Cancer Clinic in Institute of Oncology in Warsaw using a questionnaire consisting of: Demographic, Hospital Anxiety and Depression Scale (HADS), Multidimentional Health Locus of Control (MHLC), Cognitive Emotions Regulations Questionaire (CERQ). RESULTS: Seventy-eight patients aged 22 to 82 (average 54) were examined. Investigation of relationships between anxiety and depression and coping strategies showed: positive correlation of anxiety with self blame and rumination, positive correlation of anxiety and depression with catastrophizing, positive correlation of depression with blaming others, negative correlation of anxiety and depression with acceptance and positive refocusing, negative correlation of depression with refocus of planning and putting into perspective. CONCLUSIONS: The results of this study indicate that there may be an indirect method of diagnosing anxiety and depression disorders in cancer patients by observing the coping strategies to cope with the difficult situation. PMID- 27358599 TI - The incidence of breast cancer in population of young women from Podkarpackie province in 2002-2011. AB - INTRODUCTION: Breast cancer (BC) in young women of Podkarpackie province accounts for approximately 11.0% of all diagnosed breast tumors. AIM OF THE STUDY: Aim of the study was to assess the trends in incidence of BC among women younger than 44 from Podkarpackie in the years 2002-2011. MATERIAL AND METHODS: 614 cases of malignant BC and 26 cases of cancer in situ were analyzed. The crude and the standardized incidence ratios were estimated; the percentage of histopathologically confirmed cancer cases and the percentage share of registered malignant breast tumors were calculated. The analysis of incidence in individual counties was also presented, as well as the stages of clinical advancement at diagnosis and the methods of treatment. RESULTS: The number of registered cases at 2011 was 73, and it was 37.7% higher as compared to 2002. During the period analyzed, the increase in the crude and the standardized cancer incidence ratios was observed. The percentage share of BC in the examined group increased of 5.4% in 2011. Significant variation in incidence among different counties was observed. The incidence ratios ranged from 65.8 to 93.1/100 000. BC in young women most commonly was diagnosed as locally advanced and over 70% of patients were radically treated. CONCLUSIONS: Even though the progress in diagnostics and treatment has been made, BC in young women is diagnosed later than it should be and at considerably advanced stage. It is relevant to propagate the knowledge among women and health professionals to emphasize that BC may affect young women. PMID- 27358600 TI - Association between breast cancer and tumour necrosis factor-related apoptosis inducing ligand (TRAIL) gene 1595C/T SNP in a Pakistani population. AB - AIM OF THE STUDY: TRAIL-mediated signalling has emerged as an extensively studied biological mechanism reported to differentially induce apoptosis in cancer cells. However, overwhelmingly increasing experimentally verified data is shedding light on resistance against TRAIL-induced apoptosis in cancer cells. Moreover, genetic and epigenetic mutations also exert effects on the functionality of TRAIL and its receptors. In this study we investigated the association between breast cancer and polymorphisms in tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in a Pakistani Population. MATERIAL AND METHODS: Genotyping for TRAIL gene 1595 C/T polymorphism was done for 363 breast cancer patients and 193 age- and sex-matched healthy controls. DNA was extracted using standard organic methods. PCR-RFLP analysis was done for C/T polymorphism at position 1595 in exon 5 of the TRAIL gene using site-specific primers and restriction enzyme. The results were statistically evaluated by SPSS14. RESULTS: In this study, CC homozygotes were 46.3% in patients and 49.7% in controls, p = 0.729 with OR value 0.8705 (95% CI: 0.6137-1.2348). CT was statistically insignificant, p = 0.837 with OR value 0.9242 (95% CI: 0.6494-1.3154). However, the minor allele or risk allele genotype TT had a higher percentage among breast cancer patients (12.1%) than in the control group (6.7%). Since there was a statistically insignificant difference (p = 0.212, OR value 1.9098 with 95% CI 1.0019 to 3.6406) of TT genotype between the two groups, the contrastingly higher percentage of TT genotype in breast cancer patients seems to be a risk factor for the disease. Moreover, the frequency of minor allele T was also found to be higher in the patients (0.329) than in the controls (0.285). CONCLUSIONS: The TRAIL gene 1595 C/T SNP has a contradictory role in cancer development in different populations. In our population group although the percentage of homozygous risk allele TT was higher in patients it was statistically non-significant. The raised T allele and TT genotype in patients may suggest its association with breast cancer in the Pakistani population. PMID- 27358601 TI - An old enemy not to be forgotten during PET CT scanning of cancer patients: tuberculosis. AB - AIM OF THE STUDY: Positron emission tomography-computed tomography (PET CT) scan is commonly used in current medical oncology practice as an imaging method. In this study we present data from cancer patients who were followed at our clinic and suspected of having tuberculosis during PET CT scanning. After the biopsy, they were diagnosed with concomitant tuberculosis. MATERIAL AND METHODS: In this study, 14 patients who applied to our clinic and followed up due to cancer, and had PET CT scanning for the preliminary staging or further evaluation, were included. The patients were diagnosed with metastatic or recurrent disease, and their biopsy results revealed tuberculosis. RESULTS: The mean age was 57.8 years with SD (standard deviation) 13.1 years and gender distribution of 78.6% (n = 11) females and 21.4% (n = 3) males. None of the patients had tuberculosis in their personal history (0%). Among the patients, 5 (35.7%) were diagnosed with tuberculosis during the preliminary staging, whereas 9 (64.3%) were diagnosed during the follow-up after the treatment. The median time to tuberculosis diagnosis was 11 months (min-max: 3-24 months) after the treatment. The most commonly involved lymph nodes during PET CT scanning were mediastinal in 8 (64.3%), axillary in 3 (21.4%) and para-aortic in 3 (21.4%) patients. The mean SUVmax (maximum standardised uptake value) of lymph node involved by PET CT scanning was defined as 8.5 (SD 2.6). CONCLUSIONS: Despite all improvements in modern medicine, tuberculosis is still a serious public health problem. It should always be considered in differential diagnosis while evaluating PET CT scanning results of cancer patients, because it may cause false positive results. PMID- 27358602 TI - Recon 2.2: from reconstruction to model of human metabolism. AB - INTRODUCTION: The human genome-scale metabolic reconstruction details all known metabolic reactions occurring in humans, and thereby holds substantial promise for studying complex diseases and phenotypes. Capturing the whole human metabolic reconstruction is an on-going task and since the last community effort generated a consensus reconstruction, several updates have been developed. OBJECTIVES: We report a new consensus version, Recon 2.2, which integrates various alternative versions with significant additional updates. In addition to re-establishing a consensus reconstruction, further key objectives included providing more comprehensive annotation of metabolites and genes, ensuring full mass and charge balance in all reactions, and developing a model that correctly predicts ATP production on a range of carbon sources. METHODS: Recon 2.2 has been developed through a combination of manual curation and automated error checking. Specific and significant manual updates include a respecification of fatty acid metabolism, oxidative phosphorylation and a coupling of the electron transport chain to ATP synthase activity. All metabolites have definitive chemical formulae and charges specified, and these are used to ensure full mass and charge reaction balancing through an automated linear programming approach. Additionally, improved integration with transcriptomics and proteomics data has been facilitated with the updated curation of relationships between genes, proteins and reactions. RESULTS: Recon 2.2 now represents the most predictive model of human metabolism to date as demonstrated here. Extensive manual curation has increased the reconstruction size to 5324 metabolites, 7785 reactions and 1675 associated genes, which now are mapped to a single standard. The focus upon mass and charge balancing of all reactions, along with better representation of energy generation, has produced a flux model that correctly predicts ATP yield on different carbon sources. CONCLUSION: Through these updates we have achieved the most complete and best annotated consensus human metabolic reconstruction available, thereby increasing the ability of this resource to provide novel insights into normal and disease states in human. The model is freely available from the Biomodels database (http://identifiers.org/biomodels.db/MODEL1603150001). PMID- 27358603 TI - Participation in formal learning activities of older Europeans in poor and good health. AB - Little attention has been given to the involvement in formal learning activities (FLA) in the older population when considering different health statuses. The aim of this study is to explore the extent to which possible predictors (derived from previous research as well as a conceptual model) of FLA differ for older people in poor and good health. Data are used from SHARE 2010/2011 for the 50+ populations in 16 European countries. Poor health is defined as self-report of having two or more chronic diseases assessed by a medical doctor, i.e. multimorbidity. Possible predictors of learning activities represent individual characteristics: functional limitations, demography (age, gender, marital status and household size), human capital (achieved level of education), employment, income and participation in other social activities. To assess the predictors of FLA, logistic regression models are used and average marginal estimates are compared across groups. In addition to multimorbidity, labour market activity is used as a grouping variable. The average participation of individuals in the group with multimorbidity was nearly 50 % lower than that in the group in good health (6.5 vs. 13.3 %). Regardless of multimorbidity, human capital proved to be significant predictors of FLA, especially in those active on the labour market. However, the associations were weaker in the multimorbidity group. Also, significant associations were observed of other types of social activities, in particular cultural and leisure activity and volunteering, with FLA. This study suggests that similar factors are predictors of FLA in older people with and without multimorbidity. PMID- 27358604 TI - Predictors of social leisure activities in older Europeans with and without multimorbidity. AB - Older people spend much time participating in leisure activities, such as taking part in organized activities and going out, but the extent of participation may differ according to both individual and environmental resources available. Chronic health problems become more prevalent at higher ages and likely necessitate tapping different resources to maintain social participation. This paper compares predictors of participation in social leisure activities between older people with and those without multimorbidity. The European Project on Osteoarthritis (EPOSA) was conducted in Germany, UK, Italy, The Netherlands, Spain and Sweden (N = 2942, mean age 74.2 (5.2)). Multivariate regression was used to predict social leisure participation and degree of participation in people with and without multimorbidity. Fewer older people with multimorbidity participated in social leisure activities (90.6 %), compared to those without multimorbidity (93.9 %). The frequency of participation was also lower compared to people without multimorbidity. Higher socioeconomic status, widowhood, a larger network of friends, volunteering, transportation possibilities and having fewer depressive symptoms were important for (the degree of) social leisure participation. Statistically significant differences between the multimorbidity groups were observed for volunteering and driving a car, which were more important predictors of participation in those with multimorbidity. In contrast, self-reported income appeared more important for those without multimorbidity, compared to those who had multimorbidity. Policies focusing on social (network of friends), physical (physical performance) and psychological factors (depressive symptoms) and on transportation possibilities are recommended to enable all older people to participate in social leisure activities. PMID- 27358606 TI - Trajectories of vision in older people: the role of age and social position. AB - Visual impairment becomes more prevalent with age. Rather than a uniform decline in vision with age, the strength and direction of change varies between people. This study applies an analytical method that posits multiple trajectories in eyesight, allowing for a more specific description of developmental course of this health outcome and its relationship with social position. The analysis uses the responses of 2956 respondents, aged 60 years and over, followed over 8 years (five observations) as part of the English longitudinal study of ageing. At each observation respondents self-reported their general vision. Optimal matching (sequence analysis), hierarchical clustering, and multinomial logistic regression were used to describe the sequential data, produce a typology of vision trajectories, and examine the socio-demographic characteristics associated with different trajectories. Eight distinctive clusters of trajectories were identified. The probability of reporting different types of vision trajectory varies with a change in age; however, the magnitude of the age effect is associated with social position. Visual impairment in older people is an increasingly relevant area for policy focus, with the rapid growth and diversity of the older population. Identifying factors underpinning the patterning of changes in visual function is essential for developing evidence-based policy, which both meets the needs of those most at risk and increases cost-effectiveness of public health interventions. PMID- 27358605 TI - Predictors of religious participation of older Europeans in good and poor health. AB - Religious attendance is an important element of activity for older Europeans, especially in more traditional countries. The aim of the analysis is to explore whether it could be an element contributing to active ageing as well as to assess differences between the religious activity of older individuals with and without multimorbidity defined as an occurrence of two or more illnesses. The analysis is conducted based on the SHARE database (2010-2011) covering 57,391 individuals 50+ from 16 European countries. Logistic regressions are calculated to assess predictors of religious activity. Results point that religious activity often occurs in multimorbidity what could be driven by the need for comfort and compensation from religion. It is also significantly correlated with other types of social activities: volunteering or learning, even among the population with multimorbidity. There is a positive relation between religious activity and age, although its effect is weaker in the case of multimorbidity, as well as being female. Mobility limitations are found to decrease religious participation in both morbidity groups and might be related to discontinuation of religious practices in older age. The economic situation of older individuals is an insignificant factor for religious attendance. Religious attendance can be an element of active ageing, but also a compensation and adaptation to disadvantages occurring in older age and multimorbidity. At the same time, religious activities are often provided at the community level and targeted to population in poorer health. PMID- 27358607 TI - Association of type of birth attendant and place of delivery on infant mortality in sub-Saharan Africa. AB - OBJECTIVE: To examine the association between type of birth attendant and place of delivery, and infant mortality (IM). METHODS: This cross-sectional study used self-reported data from the Demographic Health Surveys for women in Ghana, Kenya, and Sierra Leone. Logistic regression estimated odds ratios (ORs) and95% confidence intervals. RESULTS: In Ghana and Sierra Leone, odds of IM were higher for women who delivered at a health facility versus women who delivered at a household residence (OR=3.18, 95% confidence interval, CI: 1.29-7.83, p=0.01 and OR=1.62, 95% CI: 1.15-2.28, p=0.01, respectively). Compared to the use of health professionals, the use of birth attendants for assistance with delivery was not significantly associated with IM for women in Ghana or Sierra Leone (OR=2.17, 95% CI: 0.83-5.69, p=0.12 and OR=1.25, 95% CI: 0.92-1.70, p=0.15, respectively). In Kenya, odds of IM, though nonsignificant, were lower for women who used birth attendants than those who used health professionals to assist with delivery (OR=0.85, 95% CI: 0.51-1.41, p=0.46), and higher with delivery at a health facility versus a household residence (OR=1.29, 95% CI: 0.81-2.03, p=0.28). CONCLUSIONS: Women in Ghana and Sierra Leone who delivered at a health facility had statistically significant increased odds of IM. Birth attendant type-IM associations were not statistically significant.Future research should consider culturally-sensitive interventions to improve maternal health and help reduce IM. PMID- 27358608 TI - Factors associated with institutional delivery in Dangila district, North West Ethiopia: a cross-sectional study. AB - INTRODUCTION: Childbirth in a health institution has been shown to be associated with lower rates of maternal and neonatal mortality. However, about 85% of mothers in Ethiopia deliver at home. OBJECTIVE: To assess factors associated with institutional delivery service utilization among women who gave birth within one year prior to the study in Dangila district. METHODS: A cross-sectional study was conducted from February 01-28, 2015. A total of 763 mothers were interviewed using structured questionnaire. SPSS version 20 was used for analysis. Crude and adjusted Odds ratios were computed for selected variables. A P-value less than 0.05 was considered statistical significant. RESULTS: Only 18.3% of mothers gave birth at health facilities. Knowledge on danger signs [AOR=2.0, 95% CI: (1.1, 3.4)], plan to give birth at health institution [AOR=5.4, 95% CI: (3.0, 9.6)], having ANC follow up during pregnancy [AOR=12.9, 95% CI: (5.0, 33.3)] and time taken to get to a nearby health institution [AOR=5.1, 95% CI: (2.9, 9.1)] were associated with institutional delivery service utilization. CONCLUSION: Institutional delivery was very low. Knowledge about danger signs, having ANC visits, and time were factors associated with institutional delivery service utilization. Thus, the findings recommend repeated re-enforcement of institutional delivery service utilization through professionals. And also, the findings recommend promotion of institutional delivery service utilization through mass media. PMID- 27358609 TI - Indirect child mortality estimation technique to identify trends of under-five mortality in Ethiopia. AB - BACKGROUND: In sub-Saharan African countries, the chance of a child dying before the age of five years is high. The problem is similar in Ethiopia, but it shows a decrease over years. METHODS: The 2000; 2005 and 2011 Ethiopian Demographic and Health Survey results were used for this work. The purpose of the study is to detect the pattern of under-five child mortality overtime. Indirect child mortality estimation technique is adapted to examine the under-five child mortality trend in Ethiopia. RESULTS: From the result, it was possible to see the trend of under-five child mortality in Ethiopia. The under-five child mortality shows a decline in Ethiopia. CONCLUSION: From the study, it can be seen that there is a positive correlation between mother and child survival which is almost certain in any population. Therefore, this study shows the trend of under-five mortality in Ethiopia and decline over time. PMID- 27358610 TI - Tobacco and alcohol use in adolescents with unplanned pregnancies: relation with family structure, tobacco and alcohol use at home and by friends. AB - BACKGROUND: Recent publications show that smoking and alcohol use among adolescents with unplanned pregnancy is increasing and the causes need to be further studied. OBJECTIVE: To determine the association between living in a non intact family household and the presence of smokers and consumers of alcoholic beverages in the adolescents' environment with smoking and consuming alcoholic beverages in adolescents with unplanned pregnancies. METHODS: A cross-sectional study was carried out among 785 pregnant adolescents, aged 13-19 years. Data was collected by trained interviewers using a self-administered questionnaire. The association was determined using multivariate logistic regression analysis. RESULTS: In adolescents with unplanned pregnancies, the prevalence of active smoking was 21.2% and of alcohol consumption, 41.5%. The percentage of smoking at home was 57.4% and alcohol consumption, 77.5%. Approximately, 80.3% of adolescents with unplanned pregnancies had friends who smoked and 90.6% consumed alcoholic beverages. Multivariate logistic regression analysis shows that having friends who smoke or who consume alcoholic beverages is the most important risk factor for substance use in adolescents with unplanned pregnancies. Smoking and alcohol consumption at home are not associated with smoking in adolescents with unplanned pregnancies. CONCLUSION: Socializing with friends who smoke and/or consume alcoholic beverages constitutes the most important risk factor for substance use among adolescents with unplanned pregnancies. PMID- 27358611 TI - Vitamin D status in the first-trimester: effects of Vitamin D deficiency on pregnancy outcomes. AB - OBJECTIVE: To assess serum levels of 25-hydroxyvitamin D [25(OH)D] in the first trimester and to determine the factors affecting deficiency levels and its association with pregnancy outcomes. METHODS: Serum 25(OH)D concentrations were measured at 11-14 weeks' gestation in 229 singleton pregnancies using liquid chromatography-tandem mass spectrometry. RESULTS: The median serum 25(OH)D concentration was 10.8 ng/mL and 45.9% of women had severe vitamin D deficiency with concentrations of <10 ng/mL. Logistic regression analysis revealed that covered dressing style, lack of multivitamin intake, season of blood sampling (November-April) were factors associated with 25(OH)D deficiency. There was a negative correlation between 25(OH)D levels and gestational age at sampling. Low 25(OH)D levels were not associated with adverse pregnancy outcomes. Higher rate of cesarean section (CS) was noted in women with 25(OH)D >=10 ng/mL compared to those with 25(OH)D < 10mg/ml (p= 0.01). CONCLUSION: A high prevalence of vitamin D deficiency was observed in early pregnancy which was related to dress code, use of multi-vitamins and season at sampling. Low 25(OH)D levels were not related with adverse pregnancy outcomes. Women with severe vitamin D deficiency were more likely to deliver vaginally. PMID- 27358612 TI - Exclusive breastfeeding practices in the Coast region, Tanzania. AB - BACKGROUND: Although breastfeeding in general is common and culturally accepted in many sub-Saharan countries, recommended exclusive breastfeeding infants to 6 months is rare. In rural Tanzania, data on infant feeding practices is rare. OBJECTIVE: To examine and describe exclusive breastfeeding practices in rural settings (Coast Region) of Tanzania. METHODS: A cross-sectional study was conducted in Coast Region of Tanzania involving 342 mothers. Only mothers with children aged between 6 and 23 months were interviewed in their residences. Data analyses included descriptive and logistic regression analyses. RESULTS: The majority, 66%, of mothers reported to have breastfed their new born within the first hour of life. About 30% reported to have breastfed exclusively for up to at least six months. Those who did not practice complete exclusive breastfeeding mentioned insufficient milk as the main reason. Correlates of exclusive breastfeeding included maternal education and attitudes towards exclusive breastfeeding. CONCLUSION: The rate of exclusive breastfeeding in rural areas like the Coast Region of Tanzania is still very low. Programs aimed to promote exclusive breastfeeding must take multi-factorial considerations. PMID- 27358613 TI - Flexible bronchoscopy contribution in the approach of diagnosis and treatment of children's respiratory diseases: the experience of a unique pediatric unit in Tunisia. AB - OBJECTIVE: Our study aimed at assessing the role of flexible bronchoscopy (FB) in improving diagnosis and management of children's respiratory conditions in the pediatric unit of FB, newly created and unique in Tunisia. METHODS: Retrospective study including all the FB achieved in our pediatric unit from 2009 to 2014. RESULTS: We performed 365 FB in 333 patients aged 46 months on average (1 month - 15 years), often under conscious anesthesia (81.6%). FB was performed for diagnostic purposes in 341 cases and for therapeutic purposes in 24 cases. Eight anatomical abnormalities were revealed in 22 patients. An intraluminal bronchial obstruction was found in 71 FB, mainly due to a foreign body (n=36). A vascular anomaly was responsible for nine cases out of 17 extraluminal obstructions. Airways malacia was observed in 60 FB. Bronchoalveolar lavage was performed in 196 cases. It was determinant in 43.9% of the cases. FB was of great diagnostic value in 74.8% of the cases. It influenced the management of the patients in 58% of the cases. The FB for therapeutic purposes was beneficial in all cases. Few complications occurred (5.5%). CONCLUSION: FB is a safe tool providing precious diagnostic and/or therapeutic help for the clinician. PMID- 27358614 TI - Iron deficiency anaemia among apparently healthy pre-school children in Lagos, Nigeria. AB - BACKGROUND: Iron deficiency, and specifically iron deficiency anaemia, remains one of the most severe and important nutritional deficiencies in the world today. OBJECTIVE: To estimate the prevalence and associated factors for iron deficiency anaemia among pre-school children in Lagos. METHODOLOGY: The study was conducted from December 2009 to February 2010 at the outpatient clinics of Lagos State University Teaching Hospital, Lagos. Serum iron, total iron binding capacity, transferrin saturation and serum ferritin were assayed in subjects. The primary outcome measured was iron deficiency anaemia established based on the following criteria: hemoglobin <11.0 g/dl1 plus 2 or more of the following: MCV <70fl, transferrin saturation <10% or serum ferritin <15ng/dL. Statistical analysis included Pearson Chi square analysis and logistic regression analysis. RESULTS: A total of 87 apparently healthy subjects were recruited. Only one subject had iron depletion and this child belonged to the <= 2 years age category. None of the recruited subjects had iron deficiency without anaemia. Nine of the study subjects (10.11%) had iron deficiency anaemia. The prevalence of iron deficiency anaemia was significantly higher among younger age group than in the older age group (19.1% Vs 2.1%, p = 0.022). The prevalence of iron deficiency anaemia was significantly higher among subjects with weight-for-age, and weight-for-height Z scores below two standard scores (83.3% and 75.0% respectively, p = <0.001 and 0.001 respectively). CONCLUSION: The overall prevalence of iron deficiency anaemia among study subjects was 10.11%. Iron deficiency anaemia was more common in children aged two years and below. Weight-for-age and weight-for-height Z scores below minus two standard scores were strongly associated with iron deficiency anaemia. PMID- 27358615 TI - A study of asymptomatic bacteriuria in Egyptian school-going children. AB - BACKGROUND: Urinary tract infections (UTI) are a common and important clinical problem in childhood. Upper urinary tract infections (i.e., acute pyelonephritis) may lead to renal scarring, hypertension, and end-stage renal disease. Despite the presence of simple and reliable methods of preliminary screening of children's urine, urinary tract infection continues to be under diagnosed. OBJECTIVES: The aim of this study was to establish prevalence rates of significant bacteriuria in asymptomatic school children by simple urine tests in comparison to standard urine culture techniques in Giza, Egypt. PATIENTS AND METHODS: A total of 1000 apparently healthy school going children (6-12) years, 552 boys (55.2%) and 448 girls (44.8%), were enrolled in this cross-sectional prevalence survey. RESULTS: Overall prevalence of significant bacteriuria was 6%. Higher prevalence occurred in girls (11.4%) than boys (1.6%). Escherichia coli was isolated in 35(58%) cases (3 boys and 32 girls), Staph. aureus in 13 (22%) cases (3 boys and 10 girls), Enterobacter in 6 girls (10%), Kelbsiella pneumoniae in 3 boys (5%) and Proteus vulgaris in 3 girls (5%). CONCLUSION: Asymptomatic bacteriurea could be detected by urine screening program at school age. Overall prevalence of significant bacteriuria was 6%, with predominance in girls than boys. PMID- 27358616 TI - Outcome of childhood malignancies at the University of Port Harcourt Teaching Hospital: a call for implementation of palliative care. AB - BACKGROUND: Cancers in children are yet to be recognised as an important cause of childhood morbidity and mortality in developing countries where more than 70% of the world annual cases occur. Despite the limited resources and whatever the projected outcome, children with cancer need treatment, be it curative or palliative. OBJECTIVES: To determine outcome of cancers in children at the UPTH; identify factors that influence outcome, highlight the need for palliative care. METHOD: A retrospective study of cases of childhood malignancies admitted into Paediatric Oncology unit of UPTH over a two year period. Clinical profile of patients and outcome were analyzed using SPSS version 20.0. RESULTS: Sixty cases were analysed: 35(58.3%) males, 25(41.7%) females giving a M:F ratio of 1.4:1. Under-fives constituted 55%. Twenty-seven (45%) patients presented within 4 weeks of onset of symptoms. Median duration of symptoms before presentation was 8 weeks while 36 (60%) had metastatic disease at diagnosis. Twenty patients (33.3%) defaulted with or without specific treatment. Mortality was recorded in 26(43.4%) of cases. CONCLUSION: There were more cases of cancer amongst under-fives with male preponderance. Late presentation, financial constraints and high default rate were contributory factors to poor outcome in most cases. Lack of palliative care left many families to face their sufferings. PMID- 27358617 TI - Hookworm-like eggs in children's faecal samples from a rural area of Rwanda. AB - BACKGROUND: Hookworm eggs identification and quantification is usually carried out by Kato-Katz method. However various structures present in the smear may be confused with eggs of such parasites. OBJECTIVE: To document the presence of structures in Kato-Katz slides that could initially be misinterpreted as hookworm eggs. METHOD: 497 faecal samples were analysed by Kato-Katz technique, diphasic concentration technique, agar-plate coprocultive and larvae obtained were analysed by PCR and characterized by sequencing. RESULT: Hookworm-like eggs were found in 159 (32%) of the samples by Kato-Katz, finally identified as Caenorhabditis elegans by PCR technique. CONCLUSION: The diagnosis of human hookworm eggs, only by the use of Kato-Katz technique can lead to false positives because of similarities with eggs of other free-living worms, from wet soils like those of Rwanda that could contaminate stool samples. PMID- 27358618 TI - A demonstration of mobile phone deployment to support the treatment of acutely ill children under five in Bushenyi district, Uganda. AB - BACKGROUND: Benefits of mobile phone deployment for children <5 in low-resource settings remain unproven. The target population of the current demonstration study in Bushenyi District, Uganda, presented with acute fever, pneumonia, or diarrhoea and were treated by community health workers (CHWs) providing integrated community case management (iCCM). METHODS: An observational study was conducted in five parishes (47 villages) served by CHWs well versed in iCCM with supplemental training in mobile phone use. Impact was assessed by quantitative measures and qualitative evaluation through household surveys, focus group discussions, and key informant interviews. RESULTS: CHWs in targeted sites improved child healthcare through mobile phone use coupled with iCCM. Of acutely ill children, 92.6% were correctly managed. Significant improvements in clinical outcomes compared to those obtained by CHWs with enhanced iCCM training alone were unproven in this limited demonstration. Nonetheless, qualitative evaluation showed gains in treatment planning, supply management, and logistical efficiency. Provider confidence and communications were enhanced as was ease and accuracy of record keeping. CONCLUSION: Mobile phones appear synergistic with iCCM to bolster basic supportive care for acutely ill children provided by CHWs. The full impact of expanded mobile phone deployment warrants further evaluation prior to scaling up in low-resource settings. PMID- 27358620 TI - A comparison of risky sexual behaviours between circumcised and uncircumcised men aged 30-44 years in Botswana. AB - BACKGROUND: The principal mode of HIV transmission in Southern Africa is through sexual intercourse, and this has prompted uptake of safe male circumcision. Engaging in risky sexual behaviour by circumcised men increases the risks of acquiring HIV, though male circumcision coupled with preventive behaviour reduces this risk. OBJECTIVE: To compare the factors associated with risky sexual behaviour among circumcised and uncircumcised men in Botswana. METHODS: Nationally representative data from the Botswana AIDS Impact Survey III were used. A sample of 313 sexually active men was used. The data was analysed by cross-tabulation and logistic regression. RESULTS: The study revealed that uncircumcised men (odds ratio, 5.711) were more likely to have sex while intoxicated with alcohol compared to circumcised men. Low levels of education (odds ratio, 8.736), urban residency (city/town: odds ratio, 1.238 and urban village: odds ratio, 1.098) were more likely to influence risky behaviour (more than one sexual partner) for circumcised men. The results also show that marital status (never married) (odds ratio, 1.947) influences risky behaviour (having sex while intoxicated with alcohol) among uncircumcised men. CONCLUSION: Low level of education, place of residence and alcohol consumption influences risky sexual behaviour for both circumcised and uncircumcised men. Policies and programmes should thus focus on the attitudes underlying sexual behaviour. PMID- 27358619 TI - The association of depression status with menopause symptoms among rural midlife women in China. AB - OBJECTIVE: This study aims to evaluate the association of depression with menopausal status and some menopause symptoms (vasomotor symptoms and poor sleep). METHODS: A total of 743 participants aged 40-60 years were recruited. Depression status was evaluated by using Self-Rating Depression Scale (SDS). Sleep quality and vasomotor symptoms were evaluated by specific symptoms questionnaire. RESULTS: The prevalence of depression among participants was 11.4%. Depression was found more likely to occur in participants with poor sleep (OR, 6.02; 95%CI, 3.61, 10.03) or with vasomotor symptoms (VMS) (OR, 2.03; 95%CI, 1.20, 3.44) after controlling for age, education level, marital status, menopause status, monthly family income and chronic diseases. Menopause status was not associated with depression. Stratification analysis showed a significant association between poor sleep and depression across different menopause stages, while VMS were associated with depression only in premenopausal status. CONCLUSION: The majority of Chinese rural midlife women do not experience depression. The relationship between depression, VMS and sleep disturbances tends to change with menopausal status in Chinese rural midlife women. PMID- 27358621 TI - Knowledge and practices related to sexually transmitted infections among women of reproductive age living in Katanga slum, Kampala, Uganda. AB - BACKGROUND: Sexually transmitted infections (STIs) still stand as one of the commonest health problems affecting women of reproductive age. The knowledge and practices of STIs, among susceptible populations such as women of reproductive age, living in slums like Katanga in Kampala Uganda need to be established. METHODS: This was a cross-sectional study with 339 participants in Katanga slum. Data was collected using an interviewer administered questionnaire, entered and analysed using SPSS version 17.0. Data was summarized using frequencies for categorical data and medians for continuous data. RESULTS: Majority of the participants (71.9%) were >=25years with a mean age of 28.0(SD +/-7.0) years. The commonest symptoms known to the participants were genital itching (60%) and genital rash (14.5%). Most mentioned multiple partners (63.7%) and unprotected sex (50.7%) as predisposing factors to STIs. Knowledge on methods of prevention was high (92.3%) however, 18.8% were found positive for STIs using the syndromic approach and 82% mentioned having suffered from STIs in the past 6 months more than once. CONCLUSION: Most participants did not know about the systemic effects of STIs to their health and didnot follow the appropriate behavior patterns despite being knowledgeable about the various methods of prevention of STIs. PMID- 27358622 TI - Comparative assessment of seller's staining test (SST) and direct fluorescent antibody test for rapid and accurate laboratory diagnosis of rabies. AB - BACKGROUND: Rabies causes 55, 000 annual human deaths globally and about 10,000 people are exposed annually in Nigeria. Diagnosis of animal rabies in most African countries has been by direct microscopic examination. In Nigeria, the Seller's stain test (SST) was employed until 2009. Before then, both SST and dFAT were used concurrently until the dFAT became the only standard method. OBJECTIVE: This study was designed to assess the sensitivity and specificity of the SST in relation to the 'gold standard' dFAT in diagnosis of rabies in Nigeria. METHODS: A total of 88 animal specimens submitted to the Rabies National Reference Laboratory, Nigeria were routinely tested for rabies by SST and dFAT. RESULTS: Overall, 65.9% of the specimens were positive for rabies by SST, while 81.8% were positive by dFAT. The sensitivity of SST in relation to the gold standard dFAT was 81.0% (95% CIs; 69.7% - 88.6%), while the specificity was 100% (95% CIs; 76% 100%). CONCLUSION: The relatively low sensitivity of the SST observed in this study calls for its replacement with the dFAT for accurate diagnosis of rabies and timely decisions on administration of PEP to prevent untimely deaths of exposed humans. PMID- 27358623 TI - Impact of weight reduction program on serum alanine aminotransferase activity and immunologic response in obese hepatitis B patients. AB - BACKGROUND: Globally, chronic B viral hepatitis (HBV) is a major health problem. Obesity is a common problem among patients with HBV. Several studies have reported that obesity is an important risk factor that alters immune system response in individuals with no underlying cause of liver disease. However, there is a strong association between BMI and the human immune system among HBV patients. OBJECTIVE: This study was to examine the correlation between body mass index, serum alanine aminotransferase activity (ALT) and immunologic response in obese hepatitis B patients. MATERIAL AND METHODS: One hundred fifty male patients with chronic hepatitis B virus, their age ranged from 30 to 45 (38.64 +/- 7.12) years and their BMI ranged from 30-35 kg/m(2). All Subjects were included in two groups: The first group received weight reduction program in the form of treadmill aerobic exercises in addition to diet control whereas the second group received no therapeutic intervention. Parameters of serum alanine aminotransferase (ALT), CD3, CD4 and CD8 were quantified; Leukocyte, differential counts and body mass index (BMI) were measured before and after 3 months at the end of the study. RESULTS: There was a 24.7%, 36.8%, 30.8%, 40.7%, 28.6%, 25.9%, 33.3% and 14.3 % reduction in mean values of alanine aminotransferase (ALT), white blood cells, total neutrophil count, monocytes, CD3, CD4 , CD8 and BMI respectively in group (A) at the end of the study. In addition, there were significant differences between mean levels of the investigated parameters in groups. CONCLUSION: Based on our findings, weight loss modulates serum alanine aminotransferase and immune system parameters of patients with hepatitis B virus infection. PMID- 27358624 TI - Seasonal abundance and molecular identification of West Nile virus vectors, Culex pipens and Culex quinquefasciatus (diptera: culicidae) in Abeokuta, South-West, Nigeria. AB - BACKGROUND: West Nile virus (WNV) infection, is an arbovirus infection with high morbidity and mortality, the vector responsible for both human and animal transmission is Culex pipens complex. OBJECTIVE: To determine the species distribution and seasonal abundance of Culex pipens and Culex quinquefasciatus mosquitoes in Abeokuta, Nigeria. METHODS: Mosquitoes belonging to the Culex pipens complex were captured in three different locations located within Abeokuta Metropolis between March 2012 and January 2013. Individual species were identified using morphometric methods. Amplification of the Ace2 gene by PCR confirmed morphormetric identification of the mosquitoes. RESULTS: A total of 751 mosquitoes were captured. Culex quinquefaciatus recorded the highest distribution of vectors with 56.6% and Culex pipens 43.4% (P > 0.05). Idi aba community recorded the highest distribution of mosquito vectors with 42.9% (n=322) and Culex quinqueaciatus was more abundantly distributed with 183 mosquitoes. Aro community recorded 32% (n=240) of captured mosquitoes with Culex quinquefaciatus having a higher level of abundance and lastly Kemta with a distribution of 25.1% (n=189). CONCLUSION: Results from this study show that potential vectors of WNV abound within Abeokuta, putting residents at high risk of West Nile infection. We advocate for introduction of routine testing of WNV in Abeokuta and Nigeria. PMID- 27358625 TI - PCR-Internal Transcribed Spacer (ITS) genes sequencing and phylogenetic analysis of clinical and environmental Aspergillus species associated with HIV-TB co infected patients in a hospital in Abeokuta, southwestern Nigeria. AB - BACKGROUND: Aspergillosis has been identified as one of the hospital acquired infections but the contribution of water and inhouse air as possible sources of Aspergillus infection in immunocompromised individuals like HIV-TB patients have not been studied in any hospital setting in Nigeria. OBJECTIVE: To identify and investigate genetic relationship between clinical and environmental Aspergillus sp. associated with HIV-TB co infected patients. METHODS: DNA extraction, purification, amplification and sequencing of Internal Transcribed Spacer (ITS) genes were performed using standard protocols. Similarity search using BLAST on NCBI was used for species identification and MEGA 5.0 was used for phylogenetic analysis. RESULTS: Analyses of sequenced ITS genes of selected fourteen (14) Aspergillus isolates identified in the GenBank database revealed Aspergillus niger (28.57%), A. tubingensis (7.14%), A. flavus (7.14%) and A. fumigatus (57.14%). Aspergillus in sputum of HIV patients were Aspergillus niger, A. fumigatus, A. tubingensis and A. flavus. Also, A. niger and A. fumigatus were identified from water and open-air. Phylogenetic analysis of sequences yielded genetic relatedness between clinical and environmental isolates. CONCLUSION: Water and air in health care settings in Nigeria are important sources of Aspergillus sp. for HIV-TB patients. PMID- 27358626 TI - Antibiotics resistance of Stenotrophomonas maltophilia strains isolated from various clinical specimens. AB - BACKGROUND: A limited number of antibiotics are recommended for the therapy of Stenotrophomonas maltophilia infections due to therapy difficulties caused by its numerous mechanisms of resistance. OBJECTIVES: In this study conducted over a period of approximately 5 years we aimed to determine resistance rates of S. maltophilia based on drug classification recommended by Clinical and Laboratory Standards Institute. METHODS: A total of 118 S. maltophilia strains isolated from various clinical specimens between January 2006 and June 2012 were included in the study. BD Phoenixautomated microbiology system (Becton Dickinson, USA) was utilized for species level identification and antibiotic susceptibility testing. RESULTS: Sixty seven of S. maltophilia strains were isolated from tracheal aspirate isolates, 17 from blood, 10 from sputum, 10 from wound and 14 from other clinical specimens. Levofloxacin was found to be the most effective antibiotic against S. maltophilia strains with resistance rate of 7.6%. The resistance rates to other antibiotics were as follows: chloramphenicol 18.2%, trimethoprim sulfamethoxazole 20.3% and ceftazidime 72%. CONCLUSION: The study revealed that S. maltophilia is resistant to many antibiotics. The treatment of infections caused by S. maltophilia should be preferred primarily as levofloxacin, chloramphenicol, and TMP-SXT, respectively. PMID- 27358628 TI - Selecting candidate predictor variables for the modelling of post-discharge mortality from sepsis: a protocol development project. AB - BACKGROUND: Post-discharge mortality is a frequent but poorly recognized contributor to child mortality in resource limited countries. The identification of children at high risk for post-discharge mortality is a critically important first step in addressing this problem. OBJECTIVES: The objective of this project was to determine the variables most likely to be associated with post-discharge mortality which are to be included in a prediction modelling study. METHODS: A two-round modified Delphi process was completed for the review of a priori selected variables and selection of new variables. Variables were evaluated on relevance according to (1) prediction (2) availability (3) cost and (4) time required for measurement. Participants included experts in a variety of relevant fields. RESULTS: During the first round of the modified Delphi process, 23 experts evaluated 17 variables. Forty further variables were suggested and were reviewed during the second round by 12 experts. During the second round 16 additional variables were evaluated. Thirty unique variables were compiled for use in the prediction modelling study. CONCLUSION: A systematic approach was utilized to generate an optimal list of candidate predictor variables for the incorporation into a study on prediction of pediatric post-discharge mortality in a resource poor setting. PMID- 27358627 TI - Characteristics and management of Enterobacteriaceae harboring IMP-4 or IMP-8 carbapenemase in a tertiary hospital. AB - BACKGROUND: The emergence of Enterobacteriaceae harboring IMP-4 or IMP-8 carbapenemases is rare. We report an occurrence of Enterobacteriaceae harboring IMP-4 or IMP-8 carbapenemases in a Chinese tertiary care hospital from November 2010 to December 2012. METHODS: The clinical characteristics of 30 patients were described. The genetic relationship of isolates was determined by pulsed-field gel electrophoresis (PFGE). Carbapenemases were detected by modified Hodge test (MHT) and polymerase chain reactions (PCRs). Amplicons were sequenced and blasted to determine the genotype. RESULTS: Most infected patients were from intensive care unit and had complex and serious underlying illnesses requiring mechanical ventilation. PFGE revealed that Klebsiella pneumoniae showed two major PFGE types. Two Klebsiella oxytoca had an indistinguishable PFGE pattern, while four Enterobacter cloacae were different strains. The sequencing studies showed Enterobacteriaceae harboring IMP-4 or IMP-8 carbapenemase in the 23 infected patients. The majority of patients had infections with the carbapenemase producing Enterobacteriaceae (CPE) strain, most were successfully treated with a range of antibiotics and discharged. CONCLUSION: It is important to maintain a high index of suspicion to screen for carbapenemase-producing Enterobacteriaceae strains. Rapid identification of these strains and implementation of stringent procedures are the key to prevent major outbreaks in a hospital setting. PMID- 27358629 TI - Perceptions and risky behaviors associated with Leptospirosis in an endemic area in a village of Ubon Ratchathani Province, Thailand. AB - BACKGROUND: Leptospirosis, a disease caused by Leptospira species, a spirochaete bacterium that can develop in an appropriate environment and/or grow in human and/or animal hosts, is a serious problem for the Ministry of Public Health, Thailand. OBJECTIVE: To investigate people's perceptions and behavioral risks regarding leptospirosis infection. METHODS: The cross-sectional descriptive study collected data in May, 2013. Data on individuals' perceptions and risky behaviors concerning leptospirosis were collected from 104 completed questionnaires. RESULTS: Regarding perceptions of leptospirosis, we found them to be at a high level (97.1%) and risky behaviors regarding leptospirosis were reported at a moderate level (74.0%). The study found no correlation between perceptions and risky behaviors regarding leptospirosis (r 0.186, p-value 0.059). CONCLUSION: This study suggest that people in these areas have good knowledge about leptospirosis. However, some people have risky behavior associated with leptospirosis. Thus, a behavioral change campaign should be promoted to encourage people awareness of the dangers of such behavior. PMID- 27358630 TI - Co-occurrence of Helicobacter pylori with faecal bacteria in Nairobi river basin: public health implications. AB - INTRODUCTION: Overwhelming evidence implicates Helicobacter pylori (H. pylori) as an etiologic agent of gastrointestinal diseases including gastric cancer. The mode of transmission of this pathogen remains poorly understood. OBJECTIVE: This investigation is to establish the presence of H. pylori in the waters of the Nairobi river basin and the predictive value the presence of fecal indicator bacteria would have for H. pylori. METHODOLOGY: Physical, chemical and biological assessment of water quality of rivers in Nairobi were carried out using standard methods. H. pylori DNA in water was detected using highly specific primers of glmM gene (294pb). RESULTS: There was high presence of faecal bacteria in the waters sampled. H. pylori DNA was detected in two domestic wells and one river. The wells were located in two different regions of the water basin but influenced by similar human activities. CONCLUSION: The high presence of faecal bacteria in the waters sampled did not parallel the H. pylori detection in the same waters. H. pylori was detected in the Nairobi river basin, but there was no relationship between the numerical levels of fecal bacteria and H. pylori. PMID- 27358631 TI - Prevalence, types and factors associated with echocardiographic abnormalities among newly diagnosed diabetic patients at Mulago Hospital. AB - BACKGROUND: The prevalence of Diabetes mellitus (DM) is on a rise in sub-Saharan Africa and will more than double by 2025. Cardiovascular disease (CVD) accounts for up to 2/3 of all deaths in the diabetic population. Of all the CVD deaths in DM, 3/4 occur in sub Saharan Africa (SSA). Non invasive identification of cardiac abnormalities, such as Left Ventricular Hypertrophy (LVH), diastolic and systolic dysfunction, is not part of diabetes complications surveillance programs in Uganda and there is limited data on this problem. This study sought to determine the prevalence, types and factors associated with echocardiographic abnormalities among newly diagnosed diabetic patients at Mulago National referral hospital in Uganda. METHODS: In this cross sectional study conducted between June 2014 and December 2014, we recruited 202 newly diagnosed adult diabetic patients. Information on patients' socio-demographics, bio-physical profile, biochemical testing and echocardiographic findings was obtained for all the participants using a pre-tested questionnaire. An abnormal echocardiogram in this study was defined as the presence of LVH, diastolic and/or systolic dysfunction and wall motion abnormality. Bivariate and multivariate logistic regression analyses were used to investigate the association of several parameters with echocardiographic abnormalities. RESULTS: Of the 202 patients recruited, males were 102(50.5%) and the mean age was 46+/-15 years. Majority of patients had type 2 DM, 156(77.2%) and type 1 DM, 41(20.3%) with mean HbA1C of 13.9+/-5.3%. Mean duration of diabetes was 2 months. The prevalence of an abnormal echocardiogram was 67.8 % (95% CI 60%-74%). Diastolic dysfunction, systolic dysfunction, LVH and wall motion abnormalities were present in 55.0%, 21.8%, 19.3% and 4.0% of all the participants respectively. In bivariate logistic regression analysis, the factors associated with an abnormal echocardiogram were age (OR 1.09 [95% CI 1.06-1.12], P <0.0001), type 2 DM (OR 5.8[95% CI 2.77-12.07], P<0.0001), hypertension (OR 2.64[95% CI 1.44-4.85], P=0.002), obesity (OR 3.51[955 CI 1.25-9.84], P=0.017 and increased waist circumference (OR 1.02[95% CI 1.00-1.04], P=0.024. On Multiple logistic regression analysis, age was the only factor associated with an abnormal echocardiogram (OR 1.09[95%CI 1.05-1.15], P<0.0001). CONCLUSION: Echocardiographic abnormalities were common among newly diagnosed adults with DM. Traditional CVD risk factors were associated with an abnormal echocardiogram in this patient population. Due to a high prevalence of echocardiographic abnormalities among newly diagnosed diabetics, we recommend screening for cardiac disease especially in patients who present with traditional CVD risk factors. This will facilitate early diagnosis, management and hence better patient outcomes. PMID- 27358632 TI - Evaluation of factors affecting adherence to asthma controller therapy in chest clinics in a sub-Saharan African setting: a cross-sectional study. AB - BACKGROUND: Adherence to controller therapy in asthma is a major concern during the management of the disease. OBJECTIVE: To determine the adherence rate and identify the predictors of low adherence to asthma controller therapy. METHODS: A cross-sectional study including asthma patients was conducted from November 1, 2012 to May 31, 2013 in 4 chest clinics in Cameroon. The adherence to asthma treatment was rated using Morisky Medication Adherence Scale. A multivariate logistic regression analysis was performed for the identification of factors associated with adherence to asthma treatment. RESULTS: Among the 201 asthma patients included, 133 (66.2%) were female. The mean age of participants was 41.2 years. Sixty-one (30.3%) of the patients did not visit the chest physician during the last year prior to the study. Asthma was well controlled in 118 patients (58.7%). The prevalence of low adherence rate to asthma controller therapy was 44.8% and the absence of any chest specialist visit within the last 12 months was the only factor associated with the low adherence rate to asthma treatment (OR 5.57 ; 95% CI 2.84-10.93). CONCLUSION: The adherence rate to asthma controller therapy in Cameroon is low and it could be improved if scheduled visits are respected by patients. PMID- 27358633 TI - Prevalence, severity and risk factors of allergic disorders among people in south India. AB - BACKGROUND: Allergic disorders are not usually life-threatening conditions but they impair the person's ability to function. It thus adversely affects the psychological wellbeing and quality of life. These implications of allergic disorders can be minimized if strategies are planned for its early identification followed by appropriate interventions. OBJECTIVES: To find out the prevalence and risk factors of allergic disorders. METHODS: Data was collected by house to house survey among participants aged 18 years and above using a standardized allergy assessment questionnaire. RESULTS: Mean age of the 400 participants was 42.8+/ 14.7 years. Majority 105(26.2%) were in the age group 36 to 45 years. Majority were females 287(71.7%) and were house wives 217(54.2%). Majority of participants were of upper socio economic class 98(44.7%) out of 219 and majority were from urban areas 326(81.5%). The prevalence of allergy among participants was found to be 115(28.7%). Out of these 115, 37(32.2%) had possibility of allergy, 60(52.2%) had probability of allergy and the rest 18(15.6%) had very high likelihood for allergy. People residing in semi urban areas had increased risk of allergy (p=0.024) than those from urban areas. The prevalence of asthma was 30(7.5%) and skin allergy was 23(5.8%). Most common precipitating factors for allergy were dust exposure 103(25.8%) followed by seasonal changes 71(17.8%). Family history of allergy was associated with allergy among participants (p<0.001). Usage of firewood was associated with symptoms of respiratory allergy among participants (p=0.01). CONCLUSION: The study revealed some important determinants of allergic disorders which have important implications to frame appropriate prevention and health educational strategies. PMID- 27358634 TI - Awareness and practices on eye effects among people with diabetes in rural Tamil Nadu, India. AB - BACKGROUND: Recently eye effects of Diabetes Mellitus (DM) are an important concern due to increase in its trend especially in developing countries. OBJECTIVES: To assess the awareness related to eye effects of DM and its prevention practices among people with diabetes. METHODS: This cross sectional study was conducted from January 2013 to April 2013 in Villupuram district of Tamil Nadu, India. All 105 people with diabetes from the service area of two sub centres were included. Data on socio demographic details, history of DM, awareness on systemic complications of DM, effects of DM on eyes, practice on regular blood check-up, eye examination and source of information were collected by interview technique using a structured questionnaire. Univariate and multiple logistic regression analysis were done to assess the association of awareness of eye examination with socio-demographic variables. RESULTS: Mean age of the study population was 56.7 years. About 93 people with diabetes (88.6%) tested their blood sugar at least once in every 3 months. About 80 people with diabetes (76.2%) were aware of at least one systemic complication of DM. Although 78 (74.3%) people with diabetes were aware that DM could affect the eyes, majority of this group (68, 87.2%) did not know the specific effects of DM on eyes. In this group, about 28(35.9%) people with diabetes were not aware of the reasons for eye effects, while others mentioned that persistent high blood sugar level (n=26, 33.3%), longer duration of DM (n=14, 17.9%) and lifestyle (n=10, 12.8%) were the reasons for the eye effects of DM. Only 31 (29.5%) of them knew that their eyes must be regularly examined. People with diabetes who had post secondary and above (>10th standard) level of education had significantly higher awareness on examination of eye (Adjusted OR=19.63). CONCLUSION: Although awareness of people with diabetes on systemic effects of DM was more, their awareness on specific eye effects and need for regular screening was low. Systematic efforts are required to increase awareness on eye effects and importance of regular screening in this population. PMID- 27358635 TI - RARbeta gene methylation is a candidate for primary glioblastoma treatment planning. AB - BACKGROUND: We screened RARbeta methylation in primary glioblastoma multiforme (GBM) and the results were evaluated based on the clinical data and treatment type. OBJECTIVE: The objective of this study was to find new areas for the usage of MS-HRM applications in the determination of methylation levels in primary GBM samples and it shows the association of RARbeta methylation with the clinical outcome. METHODS: In our study, tumor samples were collected during surgical resection by the Department of Neurosurgery. The clinical and radiologic data was carefully reviewed, compared, and evaluated with the histological results. The methylation status of RARbeta was determined by using MS-HRM. RESULTS: RARbeta gene methylation was detected in 24 out of 40 cases (60%), with different quantitative methylation levels. The mean survival time was 19 months form ethylated cases and 15 months for the non-methylated cases. The survival time of the patients who received treatment was 25 months and the survival time of the patients who received radiotherapy alone or where no treatment protocol applied was 15-20 months. Therefore, a significant difference in survival rates has been observed (P<0.05). This study indicates a potential prognostic value for GBM treatment planning. CONCLUSION: Our study is the first study to investigate RARbeta methylation in primary GBMs. We conclude that the RARbeta gene could be a new prognostic and predictive candidate marker to designate the treatment protocol for primary GBMs. PMID- 27358636 TI - Diagnostic value of diffusion weighted MRI and ADC in differential diagnosis of cavernous hemangioma of the liver. AB - AIMS: To investigate the use of diffusion weighted magnetic resonance imaging (DWI) and the apparent diffusion coefficient (ADC) values in the diagnosis of hemangioma. MATERIALS AND METHODS: The study population consisted of 72 patients with liver masses larger than 1 cm (72 focal lesions). DWI examination with a b value of 600 s/mm2 was carried out for all patients. After DWI examination, an ADC map was created and ADC values were measured for 72 liver masses and normal liver tissue (control group). The average ADC values of normal liver tissue and focal liver lesions, the "cut-off" ADC values, and the diagnostic sensitivity and specificity of the ADC map in diagnosing hemangioma, benign and malignant lesions were researched. RESULTS: Of the 72 liver masses, 51 were benign and 21 were malignant. Benign lesions comprised 38 hemangiomas and 13 simple cysts. Malignant lesions comprised 9 hepatocellular carcinomas, and 12 metastases. The highest ADC values were measured for cysts (3.782+/-0.53*10(-3) mm(2)/s) and hemangiomas (2.705+/-0.63*10(-3) mm(2)/s). The average ADC value of hemangiomas was significantly higher than malignant lesions and the normal control group (p<0.001). The average ADC value of cysts were significantly higher when compared to hemangiomas and normal control group (p<0.001). To distinguish hemangiomas from malignant liver lesions, the "cut-off" ADC value of 1.800*10(-3) mm(2)/s had a sensitivity of 97.4% and a specificity of 90.9%. To distinguish hemangioma from normal liver parenchyma the "cut-off" value of 1.858*10(-3) mm(2)/s had a sensitivity of 97.4% and a specificity of 95.7%. To distinguish benign liver lesions from malignant liver lesions the "cut-off" value of 1.800*10(-3) mm(2)/s had a sensitivity of 96.1% and a specificity of 90.0%. CONCLUSION: DWI and quantitative measurement of ADC values can be used in differential diagnosis of benign and malignant liver lesions and also in the diagnosis and differentiation of hemangiomas. When dynamic examination cannot distinguish cases with vascular metastasis and lesions from hemangioma, DWI and ADC values can be useful in the primary diagnosis and differential diagnosis. The technique does not require contrast material, so it can safely be used in patients with renal failure. PMID- 27358637 TI - Malnutrition in pre-dialysis chronic kidney disease patients in a teaching hospital in Southern Nigeria. AB - BACKGROUND: Malnutrition is a complication in chronic kidney disease (CKD) known to affect quality of life and prognosis although not often diagnosed. It is associated with rapid progression to end stage renal disease (ESRD) and mortality. Early identification and treatment will slow down progression to ESRD and mortality. OBJECTIVE: To determine the prevalence and pattern of malnutrition in pre-dialysis CKD patients in Southern Nigeria. METHODS: One hundred and twenty consecutive pre-dialysis CKD and 40 control subjects without CKD were studied. Data obtained from participants were demographics, body mass index (BMI), and aetiology of CKD. Indices used to assess presence of malnutrition were low BMI, hypocholesterolaemia and hypoalbuminaemia. Statistical significance was taken at 0.05 level. RESULTS: The mean age of the CKD subjects was 48.8+/-16.6years with a male: female ratio of 1.7:1. Prevalence of malnutrition in the CKD subjects was 46.7%, higher than 27.5% observed in the controls (p=0.033). Prevalence of malnutrition increased significantly across CKD stages 2 to 5 (p=0.020). It was significantly commoner in elderly patients (p=0.047) but not significantly different between males and females(p=0.188). CONCLUSION: Malnutrition is common in pre-dialysis CKD patients even in early CKD stages. Prevalence of malnutrition increases with worsening kidney function and increasing age. PMID- 27358638 TI - Biochemical parameters response to weight loss in patients with non-alcoholic steatohepatitis. AB - BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that is capable of progressing to end-stage liver disease, but generally has a benign course. Non-alcoholic steatohepatitis (NASH) is a growing public health problem with no approved therapy. NASH projected to be the leading cause of liver transplantation in the United States by 2020. Obesity, non-insulin-dependent diabetes mellitus and hyperlipidaemia are the most common associations of the disease. Global prevalence of NASH is 10-24% amongst general population but increases to 25-75% in obese diabetic individuals. OBJECTIVE: There is an urgent need for efficient therapeutic options as there is still no approved medication. The aim of this study was to detect changes in biochemical parameters including insulin resistance, cytokines, blood lipid profile and liver enzymes following weight loss in patients with non-alcoholic steatohepatitis. MATERIALS AND METHODS: One hundred obese patients with NASH, their age between 35-50 years, body mass index (BMI) from 30 to 35 Kg/m(2) were included in the study in two subgroups; the first group (A) received moderate aerobic exercise training in addition to diet regimen , where the second group (B) received no treatment intervention. RESULTS: The mean values of leptin, TNF-alpha, IL6, IL8, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Homeostasis Model Assessment-Insulin Resistance- index (HOMA-IR), Total Cholesterol (TC), Low Density Lipoprotein Cholesterol (LDL-c) , Triglycerides (TG) and BMI were significantly decreased in group (A), where the mean value of Adiponectin and High Density Lipoprotein Cholesterol (HDL-c) were significantly increased, while there were no significant changes in group (B). Also, there was a significant difference between both groups at the end of the study. CONCLUSION: Weight loss modulates insulin resistance, adiponectin, leptin, inflammatory cytokine levels and markers of hepatic function in patients with nonalcoholic steatohepatitis. PMID- 27358639 TI - Pattern of abdominal wall herniae in females: a retrospective analysis. AB - BACKGROUND: Gender differences are expected to influence the pattern and outcome of management of abdominal wall hernias. Some of these are left to speculations with few published articles on hernias in females. OBJECTIVES: To describe the clinical pattern of abdominal wall hernias in females. METHOD: A 5 year retrospective review. RESULT: There were 181 female patients with 184 hernias representing 27.9% of the total number of hernia patients operated. Mean age was 41.66+/-24.46 years with a bimodal peak in the 1(st) and 7(th) decades. Inguinal hernia accounted for majority (50.5%) but incisional hernia predominated in the 30-49 age group, while only inguinal and umbilical hernias were seen in the first two decades (p=0.04). There was no side predilection in the cases of inguinal hernia. There were 12 (6.6%) emergency presentations, most of which occurred in the 6th decade and above and none below 30 years (p=0.02). Umbilical (4 cases) and femoral hernias (3cases) accounted for most of these cases. Incisional hernia was the commonest cause of recurrent hernias. CONCLUSION: Inguinal hernia is the commonest hernia type in females followed by incisional hernias which also accounteds for most recurrent cases. Age appears to be a risk factor for developing complications. PMID- 27358640 TI - Ocular injuries and eye care seeking patterns following injuries among cocoa farmers in Ghana. AB - BACKGROUND: The work environment of cocoa farmers exposes them to several ocular hazards that predispose them to eye diseases and injuries. However, the extent of ocular injuries and health seeking patterns following these injuries are unknown among cocoa farmers in Ghana. OBJECTIVES: To determine the prevalence of ocular injuries and health seeking behaviour following injury among cocoa farmers in Ghana. METHODS: Five hundred and fifty six participants were recruited through simple random sampling using a multistage approach from four cocoa growing districts in Ghana. A structured questionnaire was used to collect relevant information such as demography, ocular hazards and injuries experienced. An ocular examination was also conducted to assess the eye health of the participants. Descriptive and regression statistics were used to analyze the data. The rate of ocular injuries was calculated by using the number of injuries reported that resulted in lost work time/days divided by the number of worker years at risk of injury (sum of years worked in cocoa farms for all the participants). RESULTS: The rate of ocular injuries was 11.3/1000 worker years (95% CI: 9.4 - 31) which led to lost work time of 37.3/1000 worker years (95% CI: 34.1 - 40.8). The major causes of ocular injury were plants/branches (n=73, 51.1%), chemicals (n=27, 18.9%), cocoa pod/husk (n=14, 9.8%) and occurred mostly during weeding, harvesting and chemical spraying. Few (n=34, 6.1%) participants reported the use of ocular protection. Fifty-five (38.5%) participants visited the local chemical shops, while 37 (25.9%) visited hospitals/clinics for ocular treatment of their injuries. CONCLUSION: There is a high rate of ocular injuries among cocoa farmers who make insufficient use of appropriate eye care services. There is the need for eye health education among cocoa farmers in Ghana. PMID- 27358641 TI - Acute burns of the hands - physiotherapy perspective. AB - BACKGROUND: Acute burns of the hands are complex and may impact on various aspects of a person's life. Physiotherapy rehabilitation and restoration of hand function is critical for the patient's independence and re-integration into society. PURPOSE: This study aimed to explore the perceptions and experiences of physiotherapists in the management of patients with their hand burn injuries. METHOD: Five focus groups consisting of physiotherapists and physiotherapy assistants working with burn injured patients from each of the five selected public hospitals in KwaZulu-Natal were recruited. An explorative qualitative approach was adopted. RESULTS: Physiotherapists emphasised that the acute management of the hand was trivialised due to a primary focus on the survival of the burn sufferer. Therapists identified several factors that determined the patients' level of participation and motivation in therapy one of which was the procedural pain experienced. The role of the therapists' within the rehabilitation framework was found to be critical to their recovery however there appeared to be a breakdown in the collaboration and communication among health care professionals to the detriment of effective intervention. CONCLUSION: A multidisciplinary team approach is the foundation in the management of acute burn injuries and during the trajectory of the trauma care continuum. PMID- 27358642 TI - Stapedotomy and its effect on hearing - our experience with 54 cases. AB - INTRODUCTION: This study reviews the cases of stapedotomy and evaluates its effectiveness at improving hearing loss in patients with otosclerosis. MATERIALS AND METHODS: Retrospective review of patients' records who had clinical and audiometric diagnosis of otosclerosis from January to December 2012. RESULTS: A total of 54 stapedotomy surgeries (52 unilateral and 1 bilateral surgeries) were received. Average post-operative ABG for 0.5, 1, 2 and 4 KHz showed that 61.1% had complete closure of ABG ( ABG < 10 dB) compared with 1.6% preoperatively and 85.2% had closure of ABG to within 20dB compared with 4.7% preoperatively (t - 13.89, p = 0.000). More than 94% had hearing improvement and 81.5% had ABG closure greater than 10 dB postoperatively (mean gain 23.38 +/- 12.37, t = 13.89, p = 0.000). A total of 13% complications were recorded with TM perforation (5.6%) being the commonest complication. CONCLUSION: Stapedotomy is an effective surgical procedure for the treatment of otosclerosis which leads to improvement in patients' quality of life. A favorable hearing outcome can be obtained by the combination of experienced hands with minimal surgical trauma and appropriate surgical technique. PMID- 27358643 TI - A randomised controlled trial comparing the effect of adjuvant intrathecal 2 mg midazolam to 20 micrograms fentanyl on postoperative pain for patients undergoing lower limb orthopaedic surgery under spinal anaesthesia. AB - BACKGROUND: Intrathecal adjuvants are added to local anaesthetics to improve the quality of neuraxial blockade and prolong the duration of analgesia during spinal anaesthesia. Used intrathecally, fentanyl improves the quality of spinal blockade as compared to plain bupivacaine and confers a short duration of post-operative analgesia. Intrathecal midazolam as an adjuvant has been used and shown to improve the quality of spinal anaesthesia and prolong the duration of post operative analgesia. No studies have been done comparing intrathecal fentanyl with bupivacaine and intrathecal 2 mg midazolam with bupivacaine. OBJECTIVE: To compare the effect of intrathecal 2mg midazolam to intrathecal 20 micrograms fentanyl when added to 2.6 ml of 0.5% hyperbaric bupivacaine, on post-operative pain, in patients undergoing lower limb orthopaedic surgery under spinal anaesthesia. METHODS: A total of 40 patients undergoing lower limb orthopaedic surgery under spinal anaesthesia were randomized to two groups. Group 1: 2.6mls 0.5% hyperbaric bupivacaine with 0.4mls (20micrograms) fentanyl Group 2: 2.6mls of 0.5% hyperbaric bupivacaine with 0.4mls (2mg) midazolam. RESULTS: The duration of effective analgesia was longer in the midazolam group (384.05 minutes) as compared to the fentanyl group (342.6 minutes). There was no significant difference (P 0.4047). The time to onset was significantly longer in midazolam group 17.1 minutes as compared to the fentanyl group 13.2 minutes (P 0.023). The visual analogue score at rescue was significantly lower in the midazolam group (5.55) as compared to the fentanyl group 6.35 (P - 0.043). CONCLUSION: On the basis of the results of this study, there was no significant difference in the duration of effective analgesia between adjuvant intrathecal 2 mg midazolam as compared to intrathecal 20 micrograms fentanyl for patients undergoing lower limb orthopaedic surgery. PMID- 27358644 TI - Clinical spectrum of ear, nose and throat foreign bodies in North Western Nigeria. AB - BACKGROUND: Ear, nose and throat foreign bodies (FBs) are common occurrences particularly among children. This study reviewed the clinical spectrum of ENT FBs, their treatment and outcomes as seen in a tertiary health center in North Western Nigeria. METHOD: The study was a retrospective chart review of patients that were managed for FB impaction in a tertiary health institution in North Western Nigeria over a four year period. RESULT: There were 239 patients; M: F: 1.2:1. Majority of FB impaction (46.4%) occurred in children. Majority (68.7%) were otic and FBs. 18.0% of the patients had had failed attempted removal by non ENT specialists. About 25% of these patients developed complications. Majority (62.0%) of these complications occurred in the hand of non-ENT medical personnel. CONCLUSION: Ear, nose and throat foreign bodies are common in North-Western Nigeria with the highest incidence in children. Removal attempts by untrained health professionals and lack of experience in FB management predisposes to complications. Parental education on close monitoring of their children to avoid such incidences and the need to immediately seek an Otorhinolaryngologist to prevent complications are emphasized. PMID- 27358645 TI - Epidemiology of injuries in female high school soccer players. AB - BACKGROUND: Sport is a compulsory activity in schools in South Africa. Female learners participating in soccer are more vulnerable to injuries than males. OBJECTIVE: This study determined the epidemiology of injuries in female high school soccer players. METHODS: A cross sectional survey captured the epidemiology of injuries in the players. The population included 200 players from 27 high schools in one district between the ages of 14 to 19 years. A self administered questionnaire was used to collect data. RESULTS: Only 85 scholars from 8 schools participated. From the 85 respondents, 31 (36.5%) sustained injuries. Only 61 injuries were reported by the injured players. The injury prevalence for the season was 36.5%. The rate of injury was 90 per 1000 athlete exposure hours during the season. The defenders and midfielders sustained the most injuries. Most injuries reported were contact in nature. More injuries occurred during training than during matches. The lower extremity (77.8%) was injured more than the upper extremity (22.2%). The knee (22.2%) and ankle (15.9%) were the most frequently injured body parts. Muscle injury was the most commonly reported followed by bruising. CONCLUSION: Prevalence of injuries was high with the lower limb, specifically the knee and ankle being commonly injured. PMID- 27358646 TI - Lower limb and associated injuries in frontal-impact road traffic collisions. AB - OBJECTIVES: To study the relationship between severity of injury of the lower limb and severity of injury of the head, thoracic, and abdominal regions in frontal-impact road traffic collisions. METHODS: Consecutive hospitalised trauma patients who were involved in a frontal road traffic collision were prospectively studied over 18 months. Patients with at least one Abbreviated Injury Scale (AIS) >=3 or AIS 2 injuries within two AIS body regions were included. Patients were divided into two groups depending on the severity of injury to the head, chest or abdomen. Low severity group had an AIS < 2 and high severity group had an AIS >= 2. Backward likelihood logistic regression models were used to define significant factors affecting the severity of head, chest or abdominal injuries. RESULTS: Eighty-five patients were studied. The backward likelihood logistic regression model defining independent factors affecting severity of head injuries was highly significant (p =0.01, nagelkerke r square = 0.1) severity of lower limb injuries was the only significant factor (p=0.013) having a negative correlation with head injury (Odds ratio of 0.64 (95% CI: 0.45-0.91). CONCLUSION: Occupants who sustain a greater severity of injury to the lower limb in a frontal-impact collision are likely to be spared from a greater severity of head injury. PMID- 27358647 TI - Cell phone-based health education messaging improves health literacy. AB - BACKGROUND: The ubiquity of cell phones, which allow for short message service (SMS), provides new and innovative opportunities for disease prevention and health education. OBJECTIVE: To explore the use of cell phone-based health education SMS to improve the health literacy of community residents in China. METHODS: A multi-stage random sampling method was used to select representative study communities and participants >= 18 years old. Intervention participants were sent health education SMSs once a week for 1 year and controls were sent conventional, basic health education measures. Health literacy levels of the residents before and after the intervention were evaluated between intervention and control groups. RESULTS: Public health literacy scores increased 1.5 points, from 61.8 to 63.3, after SMS intervention for 1 year (P<0.01); the increase was greater for males than females (2.01 vs. 1.03; P<0.01) and for Shenzhen local residents than non-permanent residents (2.56 vs. 1.14; P<0.01). The frequency of high health literacy scores was greater for the intervention than control group (22.03% to 30.93% vs. 22.07% to 20.82%). With health literacy as a cost-effective index, the cost-effectiveness per intervention was 0.54. CONCLUSION: SMS may be a useful tool for improving health literacy. PMID- 27358648 TI - Possible inhibition of hydroxy methyl glutaryl CoA reductase activity by nicotinic acid and ergosterol: as targeting for hypocholesterolemic action. AB - OBJECTIVE: Coronary artery diseases including atherosclerosis is considered as commonest problem worldwide. Ergosterols are the main components of vegetable oils and nuts. The objective of this study was to evaluate the potential hypoplipidemic and hypocholesterolemic effects of ergosterol in combination with niacin in rats fed high fat diet (HFD). METHODS: Eighty male albino rats were included in this study divided into two main groups: Group I: Normal rats fed standard diet treated with either niacin (8.5 mg /kg b.w) or ergosterol (100 mg/Kg b.w) or both. Group II; rats fed HFD treated with either niacin (8.5 mg /kg b.w) or ergosterol (100 mg/Kg b.w) or both The feeding and treatment lasted for 8 weeks. RESULTS: A significant elevation in the levels of total cholesterol, triacylglycerol, VLDL-c, LDL-c and atherogenic factor (p<0.001) in rats fed on HFD compared with normal control while HDL-c was significantly reduced in HFD rats compared with control group. Supplementation of diet with niacin or ergosterol or combined exerts improvement in the studied parameters by lowering triacylglycerol, total cholesterol, LDL-c and atherogenic factor and elevate HDL c near to the value of control. Niacin combined with ergosterol were effective in the reduction of hydroxy methyl glutaryl-CoA reducatase (HMGCoA) compared with control (p<0.001). The combined effect was more potent than individual alone. CONCLUSION: Utilization of niacin and ergosterol may prevent the hypercholesterolemia and incidence of coronary heart diseases. These functional foods act as nutriceutical as dyslipidemics. PMID- 27358649 TI - Rationing medical education. AB - The purpose of this paper is to discuss the role of rationing in medical education. Medical education is expensive and there is a limit to that which governments, funders or individuals can spend on it. Rationing involves the allocation of resources that are limited. This paper discussed the pros and cons of the application of rationing to medical education and the different forms of rationing that could be applied. Even though some stakeholders in medical education might be taken aback at the prospect of rationing, the truth is that rationing has always occurred in one form or another in medical education and in healthcare more broadly. Different types of rationing exist in healthcare professional education. For example rationing may be implicit or explicit or may be based on macro-allocation or micro-allocation decisions. Funding can be distributed equally among learners, or according to the needs of individual learners, or to ensure that overall usefulness is maximised. One final option is to allow the market to operate freely and to decide in that way. These principles of rationing can apply to individual learners or to institutions or departments or learning modes. Rationing is occurring in medical education, even though it might be implicit. It is worth giving consideration to methods of rationing and to make thinking about rationing more explicit. PMID- 27358650 TI - Endoscopic capacity in West Africa. AB - BACKGROUND: Levels of endoscopic demand and capacity in West Africa are unclear. OBJECTIVES: This paper aims to: 1. describe the current labor and endoscopic capacity, 2. quantify the impact of a mixed-methods endoscopy course on healthcare professionals in West Africa, and 3. quantify the types of diagnoses encountered. METHODS: In a three-day course, healthcare professionals were surveyed on endoscopic resources and capacity and were taught through active observation of live cases, case discussion, simulator experience and didactics. Before and after didactics, multiple-choice exams as well as questionnaires were administered to assess for course efficacy. Also, a case series of 23 patients needing upper GI endoscopy was done. RESULTS: In surveying physicians, less than half had resources to perform an EGD and none could perform an ERCP, while waiting time for emergency endoscopy in urban populations was at least one day. In assessing improvement in medical knowledge among participants after didactics, objective data paired with subjective responses was more useful than either alone. Of 23 patients who received endoscopy, 7 required endoscopic intervention with 6 having gastric or esophageal varices. Currently the endoscopic capacity in West Africa is not sufficient. A formal GI course with simulation and didactics improves gastrointestinal knowledge amongst participants. PMID- 27358651 TI - Behavioural studies on the ethanol leaf extract of Grewia carpinifolia in Wistar rats. AB - BACKGROUND: Grewia carpinifolia is a plant commonly used in the tropics to manage various central nervous system (CNS) disorders. However, despite its widespread use no scientific work has been reported to validate these claims. OBJECTIVES: To evaluate the activity of G. carpinifolia as it affects behaviour using animal model. METHODS: Twenty five adult Wistar rats were randomly divided into five groups (A-E). Group A served as control (given only distilled water), Groups B, C, D and E were administered with single oral dose of ethanol extract of G. carpinifolia leaf at 100, 200, 400 and 800 mg/kg body weight respectively for twenty eight days consecutively. Subsequently, open field test, negative geotaxis and hanging wire test were performed. Body and brain weights were measured and histological examination of the brain was also performed. RESULTS: At the tested doses, the extract significantly increased the time spent on the hanging wire and decreased locomotor activity at 800 mg/kg. No significant difference was observed in body and brain weights of extract treated groups when compared with the control. No visible histological lesion was also observed. CONCLUSION: The plant extract may improve muscular strength at tested doses and possess CNS depressant activity at 800 mg/kg. PMID- 27358652 TI - Updates on communicable and non-communicable diseases in LMICs. PMID- 27358653 TI - DNA methylation signature of human fetal alcohol spectrum disorder. AB - BACKGROUND: Prenatal alcohol exposure is the leading preventable cause of behavioral and cognitive deficits, which may affect between 2 and 5 % of children in North America. While the underlying mechanisms of alcohol's effects on development remain relatively unknown, emerging evidence implicates epigenetic mechanisms in mediating the range of symptoms observed in children with fetal alcohol spectrum disorder (FASD). Thus, we investigated the effects of prenatal alcohol exposure on genome-wide DNA methylation in the NeuroDevNet FASD cohort, the largest cohort of human FASD samples to date. METHODS: Genome-wide DNA methylation patterns of buccal epithelial cells (BECs) were analyzed using the Illumina HumanMethylation450 array in a Canadian cohort of 206 children (110 FASD and 96 controls). Genotyping was performed in parallel using the Infinium HumanOmni2.5-Quad v1.0 BeadChip. RESULTS: After correcting for the effects of genetic background, we found 658 significantly differentially methylated sites between FASD cases and controls, with 41 displaying differences in percent methylation change >5 %. Furthermore, 101 differentially methylated regions containing two or more CpGs were also identified, overlapping with 95 different genes. The majority of differentially methylated genes were highly expressed at the level of mRNA in brain samples from the Allen Brain Atlas, and independent DNA methylation data from cortical brain samples showed high correlations with BEC DNA methylation patterns. Finally, overrepresentation analysis of genes with up-methylated CpGs revealed a significant enrichment for neurodevelopmental processes and diseases, such as anxiety, epilepsy, and autism spectrum disorders. CONCLUSIONS: These findings suggested that prenatal alcohol exposure is associated with distinct DNA methylation patterns in children and adolescents, raising the possibility of an epigenetic biomarker of FASD. PMID- 27358655 TI - Use of complementary nucleobase-containing synthetic polymers to prepare complex self-assembled morphologies in water. AB - Amphiphilic nucleobase-containing block copolymers with poly(oligo(ethylene glycol) methyl ether methacrylate) as the hydrophilic block and nucleobase containing blocks as the hydrophobic segments were successfully synthesized using RAFT polymerization and then self-assembled via solvent switch in aqueous solutions. Effects of the common solvent on the resultant morphologies of the adenine (A) and thymine (T) homopolymers, and A/T copolymer blocks and blends were investigated. These studies highlighted that depending on the identity of the common solvent, DMF or DMSO, spherical micelles or bicontinuous micelles were obtained. We propose that this is due to the presence of A-T interactions playing a key role in the morphology and stability of the resultant nanoparticles, which resulted in a distinct system compared to individual adenine or thymine polymers. Finally, the effects of annealing on the self-assemblies were explored. It was found that annealing could lead to better-defined spherical micelles and induce a morphology transition from bicontinuous micelles to onion-like vesicles, which was considered to occur due to a structural rearrangement of complementary nucleobase interactions resulting from the annealing process. PMID- 27358654 TI - Profiling genome-wide DNA methylation. AB - DNA methylation is an epigenetic modification that plays an important role in regulating gene expression and therefore a broad range of biological processes and diseases. DNA methylation is tissue-specific, dynamic, sequence-context dependent and trans-generationally heritable, and these complex patterns of methylation highlight the significance of profiling DNA methylation to answer biological questions. In this review, we surveyed major methylation assays, along with comparisons and biological examples, to provide an overview of DNA methylation profiling techniques. The advances in microarray and sequencing technologies make genome-wide profiling possible at a single-nucleotide or even a single-cell resolution. These profiling approaches vary in many aspects, such as DNA input, resolution, genomic region coverage, and bioinformatics analysis, and selecting a feasible method requires knowledge of these methods. We first introduce the biological background of DNA methylation and its pattern in plants, animals and fungi. We present an overview of major experimental approaches to profiling genome-wide DNA methylation and hydroxymethylation and then extend to the single-cell methylome. To evaluate these methods, we outline their strengths and weaknesses and perform comparisons across the different platforms. Due to the increasing need to compute high-throughput epigenomic data, we interrogate the computational pipeline for bisulfite sequencing data and also discuss the concept of identifying differentially methylated regions (DMRs). This review summarizes the experimental and computational concepts for profiling genome-wide DNA methylation, followed by biological examples. Overall, this review provides researchers useful guidance for the selection of a profiling method suited to specific research questions. PMID- 27358656 TI - Gazelles, unicorns, and dragons battle cancer through the Nanotechnology Startup Challenge. AB - On March 4th, 2016, Springer's Cancer Nanotechnology office promoted the launch of the Nanotechnology Startup Challenge in Cancer (NSC2 ). This innovation development model is a partnership among our company, the Center for Advancing Innovation (CAI), MedImmune, the global biologics arm of AstraZeneca, and multiple institutes at the National Institutes of Health (NIH). NSC2 "crowdsources" talent from around the world to launch startups with near-term, commercially viable cancer nanotechnology inventions, which were developed by the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Biomedical Imaging and Bioengineering (NIBIB). Crowdsourcing is a process in which one uses the internet to engage a large group of people in an activity, such as NSC2 . For this initiative, CAI engaged universities, industry professionals, foundations, investors, relevant media outlets, seasoned entrepreneurs, and life sciences membership organizations to request that they participate in the challenge. From this outreach, fifty-six key thought leaders have enrolled in NSC2 as judges, mentors, and/or advisors to challenge teams (http://www.nscsquared.org/judges.html). Along with crowdsourcing talent to bolt startups around NIH inventions, NSC2 will also catalyze the launch of companies around "third-party" cancer nanotechnology inventions, which were conceived and developed outside of the NIH. Twenty-eight robust teams were accepted to the challenge on March 14th, 2016. PMID- 27358657 TI - Mental Graphs. AB - I argue that Frege Problems in thought are best modeled using graph-theoretic machinery; and that these problems can arise even when subjects associate all the same qualitative properties to the object they're thinking of twice. I compare the proposed treatment to similar ideas by Heck, Ninan, Recanati, Kamp and Asher, Fodor, and others. PMID- 27358658 TI - A Mental Files Approach to Delusional Misidentification. AB - I suggest that we can think of delusional misidentification in terms of systematic errors in the management of mental files. I begin by sketching the orthodox "bottom-up" aetiology of delusional misidentification. I suggest that the orthodox aetiology can be given a descriptivist or a singularist interpretation. I present three cases that a descriptivist interpretation needs to account for. I then introduce a singularist approach, one that is based on mental files, and show how it opens the way for different and potentially more plausible accounts of these three cases. I reflect on how this mental files approach can be viewed either as a supplement to the orthodox aetiology, or as suggesting an altogether different aetiology. I end by addressing a concern surrounding the explanatory power of mental files. PMID- 27358659 TI - Attitudes and Mental Files in Discourse Representation Theory. AB - I present a concrete DRT-based syntax and semantics for the representation of mental states in the style of Kamp (1990). This system is closely related to Recanati's (2012) Mental Files framework, but adds a crucial distinction between anchors, the analogues of mental files, and attitudes like belief, desire and imagination. Attitudes are represented as separate compartments that can be referentially dependent on anchors. I show how the added distinctions help defend the useful notion of an acquaintance-based mental file against Ninan's (Inquiry 58(4):368-377 2015) recent challenge involving counterfactual de re attitudes. PMID- 27358660 TI - Next-Generation Sequencing in the Mycology Lab. AB - New state-of-the-art techniques in sequencing offer valuable tools in both detection of mycobiota and in understanding of the molecular mechanisms of resistance against antifungal compounds and virulence. Introduction of new sequencing platform with enhanced capacity and a reduction in costs for sequence analysis provides a potential powerful tool in mycological diagnosis and research. In this review, we summarize the applications of next-generation sequencing techniques in mycology. PMID- 27358661 TI - Point of Care Testing for the Diagnosis of Fungal Infections: Are We There Yet? AB - Diagnostic tools for invasive fungal infections have continuously improved within the last decades. Nowadays, cultural methods, antigen testing, and molecular tests, such as polymerase chain reaction, are widely used. These methods, however, are accompanied with different limitations as various availability, various turnaround time or high costs. A new generation of point-of-care test has shown promising results in various studies and may overcome some of these limitations. We therefore reviewed the literature for the most promising new point-of-care tests for invasive aspergillosis (Aspergillus-specific lateral-flow device test, Aspergillus proximity ligation antigen assay), cryptococcosis (cryptococcal lateral-flow assay), and for histoplasmosis (loop-mediated isothermal amplification assay). PMID- 27358663 TI - The Holy Grail of Psychiatry. AB - "Holy Grail" is a well-known metaphor for the eternal spiritual pursuit for truth and wisdom. It suggests that in order for us to find what no one has found, we must search where few have looked. In 2013, a group led by Helen Mayberg published a groundbreaking paper that sought an answer to one of the most discussed conundrums in psychiatry and neuroscience: Can specific patterns of brain activity indicate how a depressed person will respond to treatment with medication or psychotherapy? Our author examines the findings and discusses their potential impact on treatment for a public health problem that affects millions of people worldwide. PMID- 27358662 TI - Therapeutic Drug Monitoring of Posaconazole: an Update. AB - Posaconazole is a second-generation triazole agent with a potent and broad antifungal activity. In addition to the oral suspension, a delayed-release tablet and intravenous formulation with improved pharmacokinetic properties have been introduced recently. Due to the large interindividual and intraindividual variation in bioavailability and drug-drug interactions, therapeutic drug monitoring (TDM) is advised to ensure adequate exposure and improve clinical response for posaconazole. Here, we highlight and discuss the most recent findings on pharmacokinetics and pharmacodynamics of posaconazole in the setting of prophylaxis and treatment of fungal infections and refer to the challenges associated with TDM of posaconazole. PMID- 27358665 TI - Review: Leon N. Cooper's Science and Human Experience: Values, Culture, and the Mind. AB - Why are we reviewing a book written by someone who shared in the 1972 Nobel Prize in Physics for work on superconductivity? Because shortly after winning the prize, Leon N. Cooper transitioned into brain research-specifically, the biological basis of memory. He became director of the Brown University Institute for Brain and Neural Systems, whose interdisciplinary program allowed him to integrate research on the brain, physics, and even philosophy. His new book tackles a diverse spectrum of topics and questions, including these: Does science have limits? Where does order come from? Can we understand consciousness? PMID- 27358664 TI - Schizophrenia: Hope on the Horizon. AB - In July 2014, an international consortium of schizophrenia researchers co-founded by the author mounted the largest biological experiment in the history of psychiatry and found eighty new regions in the genome associated with the illness. With many more avenues for exploring the biological underpinnings of schizophrenia now available to neuroscientists, hope may be on the way for the estimated 2.4 million Americans and 1 in 100 people worldwide affected by the illness, one in which drugs have limited impact and there is no known cure. PMID- 27358666 TI - No End in Sight: The Abuse of Prescription Narcotics. AB - From teenagers dying from heroin overdoses to crime tied to Vicodin and OxyContin addiction to road fatalities in which sedatives and muscle relaxants are involved, 20,000 deaths in the United States in 2014 were attributed to problems associated with narcotics and prescription drug use. Our author, whose research involves the neurobiological basis of drug addiction, traces the history and evolution of narcotics and leans on his clinical experience to discuss why certain drugs are powerful, addicting-and dangerous. PMID- 27358667 TI - The Binge and the Brain. AB - Who hasn't dipped into that pint of Haagen-Dazs with the best of intentions and ended up finishing the entire container? Knowing where the line is when it comes to out-of-control impulse consumption is at the heart of binge-eating disorder (BED), a newly recognized mental condition that effects affects millions of people and that we are just beginning to better understand-from both a neurobiological and clinical standpoint. PMID- 27358668 TI - Body Ideals and Body Dissatisfaction Among a Community Sample of Ethnically Diverse Adolescents on Kauai, Hawaii. AB - INTRODUCTION: Body dissatisfaction (BD), a risk factor for eating disorders, is occurring at younger ages and among a wide range of socioeconomic and cultural groups. OBJECTIVE: To describe body ideals and prevalence of body satisfaction among an ethnically diverse population of male and female students in Hawaii. METHODS: An anonymous cross-sectional survey including biographical information and the figure drawing screen was distributed to 7th through 12th grade students. RESULTS: Of the 1330 completed surveys, 19% of students were significantly dissatisfied with their bodies. Males were at greater risk than females for total BD (25.8% vs. 13.3%; p<0.001) and for BD in the direction of wanting to be larger (11.3% vs. 2.3%; p<0.001). Males and females were at similar risk for BD in the direction of wanting to be thinner (14.6% vs. 11.6%; p=0.11). Prevalence of BD in the direction of wanting to be thinner was significantly different (p<0.05) among ethnic groups. There were no significant differences in BD based on grade level or SES. CONCLUSIONS: BD exists among nearly 1 out of 5 adolescents, with differing patterns for males and females, and with certain ethnic groups being at higher risk. IMPLICATIONS: Studies to understand risk and protective factors by sex and among different ethnic groups may help generate tailored prevention strategies. Further research is needed to better understand the mechanisms underlying the bidirectional BD seen in males and potential outcomes. PMID- 27358669 TI - Endoscopic management of sigmoid volvulus in children. AB - Sigmoid volvulus (SV) is extremely uncommon in children and is usually associated with a long-standing history of constipation or pseudo-obstruction. An early diagnosis and management are crucial in order to prevent the appearance of hemorrhagic infarction of the twisted loop, avoiding further complications such as necrosis, perforation and sepsis. In patients with no evidence of peritonitis or ischemic bowel, treatment starts with resuscitation and detorsion of the SV, accomplished by means of sigmoidoscopy and concomitant rectal tube placement. The bowel is then prepared and surgery is undertaken electively during the same hospitalization. We report a detailed review of the literature focusing on technical details, risks and benefits of endoscopic management of SV in childhood. PMID- 27358670 TI - Single port laparoscopic liver surgery: A minireview. AB - Nowadays, the trend is to perform surgeries with "scarless" incisions. In light of this, the single-port laparoscopic surgery (SPLS) technique is rapidly becoming widespread due to its lack of invasiveness and its cosmetic advantages, as the only entry point is usually hidden in the umbilicus. The interest in "scarless" liver resections did not grow as rapidly as the interest in other scarless surgeries. Hepatopancreatobiliary surgeons are reluctant to operate a malignant lesion through a narrow incision with limited exposure. There are concerns over adverse oncological outcomes for single-port laparoscopic liver resections (SPL-LR) for hepatocellular carcinoma or metastatic colorectal cancer. In addition, getting familiar with using the operating instruments through a narrow incision with limited exposure is very challenging. In this article, we reviewed the published literature to describe history, indications, contraindications, ideal patients for new beginners, technical difficulty, advantages, disadvantages, oncological concern and the future of SPL-LR. PMID- 27358671 TI - Effectiveness of clip-and-snare method using pre-looping technique for gastric endoscopic submucosal dissection. AB - AIM: To evaluate efficacy and safety of clip-and-snare method using pre-looping technique (CSM-PLT) for gastric endoscopic submucosal dissection (ESD). METHODS: In the CSM-PLT method, a clip attached to the lesion side was strangulated with a snare, followed by application of an appropriate tension to the lesion independent of an endoscope. Twenty consecutive lesions were resected by ESD using CSM-PLT (CSM-PLT group) and compared with a control group, including 20 lesions that were resected by conventional ESD. The control group was matched based on the size and location of the lesion, presence of pathologic fibrosis, and experience of endoscopists. Total procedure time of ESD, proportion of en bloc resection, and complications were analyzed. RESULTS: The total procedure time for the CSM-PLT group was significantly shorter than that for the control group (38.5 min vs 59.5 min, P = 0.023); all lesions were resected en bloc by ESD. There was no significant difference in complications between the two groups. Moreover, there was no complication in the CSM-PLT group. In one large lesion (size: 74 mm) that underwent extensive CSM-PLT during ESD, we used an additional CSM-PLT on another edge of the lesion after achieving submucosal resection to the maximum extent possible during initial CSM-PLT. In two lesions, the snare came off the lesion together with the clip after a sudden pull; nevertheless, ESD was successful in all lesions. CONCLUSION: CSM-PLT was an effective and safe method for gastric ESD. PMID- 27358672 TI - Strategies of laparoscopic spleen-preserving splenic hilar lymph node dissection for advanced proximal gastric cancer. AB - For advanced proximal gastric cancer (GC), splenic hilar (No. 10) lymph nodes (LN) are crucial links in lymphatic drainage. According to the 14(th) edition of the Japanese GC treatment guidelines, a D2 lymphadenectomy is the standard surgery for advanced GC, and No. 10 LN should be dissected for advanced proximal GC. In recent years, the preservation of organ function and the use of minimally invasive technology are being accepted by an increasing number of clinicians. Laparoscopic spleen-preserving splenic hilar LN dissection has become more accepted and is gradually being used in operations. However, because of the complexity of splenic hilar anatomy, mastering the strategies for laparoscopic spleen-preserving splenic hilar LN dissection is critical for successfully completing the operation. PMID- 27358674 TI - Gao's double-way approach for laparoscopic D2 radical surgery for gastric cancer. AB - Laparoscopic D2 radical surgery for gastric cancer is minimally invasive but complex. In this path: (1) Repeated operation of lesser curvature side; (2) The gastrohepatic ligament is relatively fixed. Hence, it is not easy to expose the suprapancreatic area; and (3) It is not easy to dissect No. 1, 12 lymph nodes. This area may not be sufficiently cleaned or surrounding vessels may be injured during a resection. So it is critical to choose position fixing, and a clear, fast and convenient operation path. The author, based on his experience, has established a set of procedural steps called "Gao's double-way", lesser omentum approach and traditional greater omentum approach, which are described in detail in this article. The path of this first approach is described as a "W" type of dissection. The second way is the traditional greater omentum approach, whose path is described as a "M" type of dissection. This will enable laparoscopic surgeons to select a suitable path. This new approach not only simplifies the surgery but also provides more space for the subsequent operation, thereby making the surgery more simple, safe and easy. PMID- 27358675 TI - Impact of previous cyst-enterostomy on patients' outcome following resection of bile duct cysts. AB - AIM: To analyze the impact of previous cyst-enterostomy of patients underwent congenital bile duct cysts (BDC) resection. METHODS: A multicenter European retrospective study between 1974 and 2011 were conducted by the French Surgical Association. Only Todani subtypes I and IVb were included. Diagnostic imaging studies and operative and pathology reports underwent central revision. Patients with and without a previous history of cyst-enterostomy (CE) were compared. RESULTS: Among 243 patients with Todani types I and IVb BDC, 16 had undergone previous CE (6.5%). Patients with a prior history of CE experienced a greater incidence of preoperative cholangitis (75% vs 22.9%, P < 0.0001), had more complicated presentations (75% vs 40.5%, P = 0.007), and were more likely to have synchronous biliary cancer (31.3% vs 6.2%, P = 0.004) than patients without a prior CE. Overall morbidity (75% vs 33.5%; P < 0.0008), severe complications (43.8% vs 11.9%; P = 0.0026) and reoperation rates (37.5% vs 8.8%; P = 0.0032) were also significantly greater in patients with previous CE, and their Mayo Risk Score, during a median follow-up of 37.5 mo (range: 4-372 mo) indicated significantly more patients with fair and poor results (46.1% vs 15.6%; P = 0.0136). CONCLUSION: This is the large series to show that previous CE is associated with poorer short- and long-term results after Todani types I and IVb BDC resection. PMID- 27358673 TI - Parenchymal-sparing liver surgery in patients with colorectal carcinoma liver metastases. AB - Liver resection is the treatment of choice for patients with colorectal liver metastases (CLM). However, major resections are often required to achieve R0 resection, which are associated with substantial rates of morbidity and mortality. Maximizing the amount of residual liver gained increasing significance in modern liver surgery due to the high incidence of chemotherapy-associated parenchymal injury. This fact, along with the progressive expansion of resectability criteria, has led to the development of a surgical philosophy known as "parenchymal-sparing liver surgery" (PSLS). This philosophy includes a variety of resection strategies, either performed alone or in combination with ablative therapies. A profound knowledge of liver anatomy and expert intraoperative ultrasound skills are required to perform PSLS appropriately and safely. There is a clear trend toward PSLS in hepatobiliary centers worldwide as current evidence indicates that tumor biology is the most important predictor of intrahepatic recurrence and survival, rather than the extent of a negative resection margin. Tumor removal avoiding the unnecessary sacrifice of functional parenchyma has been associated with less surgical stress, fewer postoperative complications, uncompromised cancer-related outcomes and higher feasibility of future resections. The increasing evidence supporting PSLS prompts its consideration as the gold-standard surgical approach for CLM. PMID- 27358676 TI - Predictors of long term survival after hepatic resection for hilar cholangiocarcinoma: A retrospective study of 5-year survivors. AB - AIM: To determine predictors of long term survival after resection of hilar cholangiocarcinoma (HC) by comparing patients surviving > 5 years with those who survived < 5 years. METHODS: This is a retrospective study of patients with pathologically proven HC who underwent surgical resection at the Gastroenterology Surgical Center, Mansoura University, Egypt between January 2002 and April 2013. All data of the patients were collected from the medical records. Patients were divided into two groups according to their survival: Patients surviving less than 5 years and those who survived > 5 years. RESULTS: There were 34 (14%) long term survivors (5 year survivors) among the 243 patients. Five-year survivors were younger at diagnosis than those surviving less than 5 years (mean age, 50.47 +/- 4.45 vs 54.59 +/- 4.98, P = 0.001). Gender, clinical presentation, preoperative drainage, preoperative serum bilirubin, albumin and serum glutamic-pyruvic transaminase were similar between the two groups. The level of CA 19-9 was significantly higher in patients surviving < 5 years (395.71 +/- 31.43 vs 254.06 +/- 42.19, P = 0.0001). Univariate analysis demonstrated nine variables to be significantly associated with survival > 5 year, including young age (P = 0.001), serum CA19-9 (P = 0.0001), non-cirrhotic liver (P = 0.02), major hepatic resection (P = 0.001), caudate lobe resection (P = 0.006), well differentiated tumour (P = 0.03), lymph node status (0.008), R0 resection margin (P = 0.0001) and early postoperative liver cell failure (P = 0.02). CONCLUSION: Liver status, resection of caudate lobe, lymph node status, R0 resection and CA19-9 were demonstrated to be independent risk factors for long term survival. PMID- 27358677 TI - How does epidemiological and clinicopathological features affect survival after gastrectomy for gastric cancer patients-single Egyptian center experience. AB - AIM: To investigate the clinicopathological features and the significance of different prognostic factors which predict surgical overall survival in patients with gastric carcinoma. METHODS: This retrospective study includes 80 patients diagnosed and treated at gastroenterology surgical center, Mansoura University, Egypt between February 2009 to February 2013. Prognostic factors were assessed by cox proportional hazard model. RESULTS: There were 57 male and 23 female. The median age was 57 years (24-83). One, 3 and 5 years survival rates were 71%, 69% and 46% respectively. The median survival was 69.96 mo. During the follow-up period, 13 patients died (16%). Hospital morbidity was reported in 10 patients (12.5%). The median number of lymph nodes removed was 22 (4-41). Lymph node (LN) involvement was found in 91% of cases. After R0 resection, depth of wall invasion, LN involvement and the number (> 15) of retrieved LN, LN ratio and tumor differentiation predict survival. In multivariable analysis, tumor differentiation, curability of resection and a number of resected LN superior to 15 were found to be independent prognostic factors. CONCLUSION: Surgery remains the cornerstone of treatment. Tumor differentiation, curability of resection and a number of resected LN superior to 15 were found to be independent prognostic factors. Extended LN dissection does not increase the morbidity or mortality rate but markedly improves long term survival. PMID- 27358679 TI - Solitary fibrous tumor of the pancreas: Case report and review of the literature. AB - Solitary fibrous tumor (SFT) is a mesenchymal tumor typically located in the pleura, but can also be found as an asymptomatic mass in other areas, including the liver, peritoneum, kidney and salivary glands. However, SFT rarely locates in the pancreas. We present such a case of pancreatic SFT, along with a review of all reported cases. A 55-year-old man was treated surgically for an asymptomatic pancreatic mass after a rigorous preoperative control. Histologic examination of the resected specimen showed characteristics of an SFT. As only 15 cases of pancreatic SFT have been reported so far, an attempt to compare the cases was considered intriguing. We found that patients with pancreatic SFT were mainly women (81.25%), with a median age of 54 years at the time of diagnosis and a median tumor size of 5.83 cm. Pancreatic SFTs were revealed incidentally in 50% of cases, and all of them showed an enhancement through arterial computed tomography. All tumors were positive for CD34, ten were positive for Bcl-2, and twelve were negative for S100. The diagnosis of this pancreatic tumor is established by a combination of clinical suspicion, imaging procedures and histological findings, and is confirmed by immunohistochemical staining. Although the behavior of SFTs is rather benign, close clinical follow-up is recommended due to a potentially malignant nature. PMID- 27358678 TI - Critical appraisal of laparoscopic vs open rectal cancer surgery. AB - AIM: To evaluate the long-term clinical and oncological outcomes of laparoscopic rectal resection (LRR) and the impact of conversion in patients with rectal cancer. METHODS: An analysis was performed on a prospective database of 633 consecutive patients with rectal cancer who underwent surgical resection. Patients were compared in three groups: Open surgery (OP), laparoscopic surgery, and converted laparoscopic surgery. Short-term outcomes, long-term outcomes, and survival analysis were compared. RESULTS: Among 633 patients studied, 200 patients had successful laparoscopic resections with a conversion rate of 11.1% (25 out of 225). Factors predictive of survival on univariate analysis include the laparoscopic approach (P = 0.016), together with factors such as age, ASA status, stage of disease, tumor grade, presence of perineural invasion and vascular emboli, circumferential resection margin < 2 mm, and postoperative adjuvant chemotherapy. The survival benefit of laparoscopic surgery was no longer significant on multivariate analysis (P = 0.148). Neither 5-year overall survival (70.5% vs 61.8%, P = 0.217) nor 5-year cancer free survival (64.3% vs 66.6%, P = 0.854) were significantly different between the laparoscopic group and the converted group. CONCLUSION: LRR has equivalent long-term oncologic outcomes when compared to OP. Laparoscopic conversion does not confer a worse prognosis. PMID- 27358680 TI - Gastrointestinal bleeding and obstructive jaundice: Think of hepatic artery aneurysm. AB - Hemobilia is an uncommon and potential life-threatening condition mainly due to hepato-biliary tree traumatic or iatrogenic injuries. Spontaneously ruptured aneurysm of the hepatic artery is seldom described. We report the case of an 89 year-old woman presenting with abdominal pain, jaundice and gastrointestinal bleeding, whose ultrasound and computed tomography revealed a non-traumatic, spontaneous aneurysm of the right hepatic artery. The oeso-gastro-duodenoscopy and colonoscopy did not reveal any bleeding at the ampulla of Vater, nor anywhere else. Selective angiography confirmed the diagnosis of hepatic artery aneurysm and revealed a full hepatic artery originating from the superior mesenteric artery. The patient was successfully treated by selective embolization of microcoils. We discuss the etiologies of hemobilia and its treatment with selective embolization, which remains favored over surgical treatment. Although aneurysm of the hepatic artery is rare, especially without trauma, a high index of suspicion is needed in order to ensure appropriate treatment. PMID- 27358681 TI - Enteric duplication cyst as a leading point for ileoileal intussusception in an adult: A rare cause of complete small intestinal obstruction. AB - Duplication of alimentary tract (DAT) presenting as an ileoileal intussusception is a very rare clinical entity. Herein, a case of an ileoileal intussusception due to DAT is presented. A 32-year-old woman was hospitalized due to diffuse, intermittent abdominal pain, vomiting and constipation for 3 d associated with abdominal distention. Plain abdominal X-ray revealed dilated small bowel. Abdominal computed tomography showed grossly dilated small bowel with "sausage" and "doughnut" signs of small bowel intussusception. She underwent laparotomy, with findings of ileoileal intussusception due to a cystic lesion adjacent to the mesenteric side. Resection of the cystic lesion along with the affected segment of intestine, with an end to end anastomosis was performed. The histopathology was consistent with enteric duplication cyst. This case highlights the DAT, although, an uncommon cause of adult ileoileal intussusception should be considered in the differential diagnosis of intussusception in adults, particularly when the leading point is a cystic lesion. PMID- 27358682 TI - Coronary artery anomalies overview: The normal and the abnormal. AB - The aim of this review is to give a comprehensive and concise overview of coronary embryology and normal coronary anatomy, describe common variants of normal and summarize typical patterns of anomalous coronary artery anatomy. Extensive iconography supports the text, with particular attention to images obtained in vivo using non-invasive imaging. We have divided this article into three groups, according to their frequency in the general population: Normal, normal variant and anomaly. Although congenital coronary artery anomalies are relatively uncommon, they are the second most common cause of sudden cardiac death among young athletes and therefore warrant detailed review. Based on the functional relevance of each abnormality, coronary artery anomalies can be classified as anomalies with obligatory ischemia, without ischemia or with exceptional ischemia. The clinical symptoms may include chest pain, dyspnea, palpitations, syncope, cardiomyopathy, arrhythmia, myocardial infarction and sudden cardiac death. Moreover, it is important to also identify variants and anomalies without clinical relevance in their own right as complications during surgery or angioplasty can occur. PMID- 27358683 TI - Imaging and radiological interventions in extra-hepatic portal vein obstruction. AB - Extrahepatic portal vein obstruction (EHPVO) is a primary vascular condition characterized by chronic long standing blockage and cavernous transformation of portal vein with or without additional involvement of intrahepatic branches, splenic or superior mesenteric vein. Patients generally present in childhood with multiple episodes of variceal bleed and EHPVO is the predominant cause of paediatric portal hypertension (PHT) in developing countries. It is a pre-hepatic type of PHT in which liver functions and morphology are preserved till late. Characteristic imaging findings include multiple parabiliary venous collaterals which form to bypass the obstructed portal vein with resultant changes in biliary tree termed portal biliopathy or portal cavernoma cholangiopathy. Ultrasound with Doppler, computed tomography, magnetic resonance cholangiography and magnetic resonance portovenography are non-invasive techniques which can provide a comprehensive analysis of degree and extent of EHPVO, collaterals and bile duct abnormalities. These can also be used to assess in surgical planning as well screening for shunt patency in post-operative patients. The multitude of changes and complications seen in EHPVO can be addressed by various radiological interventional procedures. The myriad of symptoms arising secondary to vascular, biliary, visceral and neurocognitive changes in EHPVO can be managed by various radiological interventions like transjugular intra-hepatic portosystemic shunt, percutaneous transhepatic biliary drainage, partial splenic embolization, balloon occluded retrograde obliteration of portosystemic shunt (PSS) and revision of PSS. PMID- 27358684 TI - Advanced multimodality imaging of inflammatory bowel disease in 2015: An update. AB - The diagnosis and effective management of inflammatory bowel disease (IBD) requires a combination clinical, endoscopic, histological, biological, and imaging data. While endoscopy and biopsy remains the gold standard for diagnosis of IBD, imaging plays a central role in the assessment of extra mural disease, in disease surveillance and in the assessment of response to medical treatments, which are often expensive. Imaging is also vital in the detection and diagnosis of disease related complications, both acute and chronic. In this review, we will describe, with illustrative images, the imaging features of IBD in adults, with emphasis on up-to-date imaging techniques focusing predominantly on cross sectional imaging and new magnetic resonance imaging techniques. PMID- 27358685 TI - Imaging in pulmonary hydatid cysts. AB - Hydatid disease is a zoonosis that can involve almost any organ in the human body. After the liver, the lungs are the most common site for hydatid disease in adults. Imaging plays a pivotal role in the diagnosis of the disease, as clinical features are often nonspecific. Classical radiological signs of pulmonary hydatid cysts have been described in the literature, aiding in the diagnosis of the disease. However, complicated hydatid cysts can prove to be a diagnostic challenge at times due to their atypical imaging features. Radiography is the initial imaging modality. Computed tomography can provide a specific diagnosis in complicated cases. Ultrasound is particularly useful in peripheral lung lesions. The role of magnetic resonance imaging largely remains unexplored. PMID- 27358686 TI - Effects of iodinated contrast on various magnetic resonance imaging sequences and field strength: Implications for characterization of hemorrhagic transformation in acute stroke therapy. AB - AIM: To characterize the effects of iodinated contrast material (ICM) on magnetic resonance imaging (MRI) comparing different sequences and magnetic fields, with emphasis to similarities/differences with well-known signal characteristics of hemorrhage in the brain. METHODS: Aliquots of iopamidol and iodixanol mixed with normal saline were scanned at 1.5T and 3T. Signal intensity (SI) was measured using similar spin-echo (SE)-T1, SE-T2, gradient-echo (GRE) and fluid-attenuation inversion-recovery (FLAIR) sequences at both magnets. Contrast to noise ratio (CNR) (SI contrast-SI saline/SD noise) for each aliquot were calculated and Kruskall-wallis test and graphic analysis was used to compare different pulse sequences and ICMs. RESULTS: Both ICM showed increased SI on SE-T1 and decreased SI on SE-T2, GRE and FLAIR at both 1.5T and 3T, as the concentration was increased. By CNR measurements, SE-T2 had the greatest conspicuity at 3T with undiluted iopamidol (92.6 +/- 0.3, P < 0.00) followed by iodixanol (77.5 +/- 0.9, P < 0.00) as compared with other sequences (CNR range: 15-40). While SE-T2 had greatest conspicuity at 1.5T with iopamidol (49.3 +/- 1, P < 0.01), SE-T1 showed similar or slightly better conspicuity (20.8 +/- 4) than SE-T2 with iodixanol (23 +/- 1.7). In all cases, hypo-intensity on GRE was less conspicuous than on SE-T2. CONCLUSION: Iodixanol and iopamidol shorten T1 and T2 relaxation times at both 1.5T and 3T. Hypo-intensity due to shortened T2 relaxation time is significantly more conspicuous than signal changes on T1-WI, FLAIR or GRE. Variations in signal conspicuity according to pulse sequence and to type of ICM are exaggerated at 3T. We postulate T2 hypointensity with less GRE conspicuity differentiates ICM from hemorrhage; given the well-known GRE hypointensity of hemorrhage. Described signal changes may be relevant in the setting of recent intra-arterial or intravenous ICM administration in translational research and/or human stroke therapy. PMID- 27358687 TI - Does computed tomography permeability predict hemorrhagic transformation after ischemic stroke? AB - AIM: To use perfusion-derived permeability-surface area product maps to predict hemorrhagic transformation following thrombolytic treatment for acute ischemic stroke. METHODS: We retrospectively analyzed our prospectively kept acute stroke database over five consecutive months for patients with symptoms of acute ischemic stroke (AIS) who had computed tomography (CT) perfusion (CTP) done at arrival. Patients included in the analyses also had to have a follow-up CT. The permeability-surface area product maps (PS) was calculated for the side of the ischemia and/or infarction and for the contralateral unaffected side at the same level. The cerebral blood flow map was used to delineate the ischemic territory. Next, a region of interest was drawn at the centre of this territory on the PS parametric map. Finally, a mirror region of interest was created on the contralateral side at the same level. The relative permeability-surface area product maps (rPS) provided an internal control and was calculated as the ratio of the PS on the side of the AIS to the PS on the contralateral side. A student t test was performed after log conversion of rPS between patients with and without hemorrhagic transformation. Log conversion was used to convert the data into normal distribution to use t-test. For the group of patients who experienced intracranial bleed, a student t-test was performed between those with only petechial hemorrhage and those with more severe parenchymal hematoma with subarachnoid haemorrhage. RESULTS: Of 84 patients with AIS and CTP at admission, only 42 patients had a follow-up CT. The rPS derived using the normal side as the internal control was significantly higher (P = 0.003) for the 15 cases of hemorrhagic transformation (1.71 + 1.64) compared to 27 cases that did not have any (1.07 + 1.30). Patients with values above the overall mean rPS of 1.3 had an increased likelihood of subsequent hemorrhagic transformation. The sensitivity of using this score to predict hemorrhagic transformation was 71.4, the specificity was 78.6, with a positive predictive value of 62.5 and negative predictive value of 84.6. The accuracy was 76.2. The odds ratio of an event occurring with such an rPS was 9.2. Of the 15 cases of hemorrhagic transformation, there was no difference (P = 0.35) in the rPS between the eight cases of petechial and the seven cases of more severe hemorrhagic events. CONCLUSION: Pretreatment PS can predict the occurrence of hemorrhagic transformation on follow-up of AIS patients with relatively high sensitivity, specificity, positive and negative predictive value. PMID- 27358688 TI - Predictive model for contrast-enhanced ultrasound of the breast: Is it feasible in malignant risk assessment of breast imaging reporting and data system 4 lesions? AB - AIM: To build and evaluate predictive models for contrast-enhanced ultrasound (CEUS) of the breast to distinguish between benign and malignant lesions. METHODS: A total of 235 breast imaging reporting and data system (BI-RADS) 4 solid breast lesions were imaged via CEUS before core needle biopsy or surgical resection. CEUS results were analyzed on 10 enhancing patterns to evaluate diagnostic performance of three benign and three malignant CEUS models, with pathological results used as the gold standard. A logistic regression model was developed basing on the CEUS results, and then evaluated with receiver operating curve (ROC). RESULTS: Except in cases of enhanced homogeneity, the rest of the 9 enhancement appearances were statistically significant (P < 0.05). These 9 enhancement patterns were selected in the final step of the logistic regression analysis, with diagnostic sensitivity and specificity of 84.4% and 82.7%, respectively, and the area under the ROC curve of 0.911. Diagnostic sensitivity, specificity, and accuracy of the malignant vs benign CEUS models were 84.38%, 87.77%, 86.38% and 86.46%, 81.29% and 83.40%, respectively. CONCLUSION: The breast CEUS models can predict risk of malignant breast lesions more accurately, decrease false-positive biopsy, and provide accurate BI-RADS classification. PMID- 27358689 TI - Contrast-enhanced ultrasound improved performance of breast imaging reporting and data system evaluation of critical breast lesions. AB - AIM: To determine whether contrast-enhanced ultrasound (CEUS) can improve the precision of breast imaging reporting and data system (BI-RADS) categorization. METHODS: A total of 230 patients with 235 solid breast lesions classified as BI RADS 4 on conventional ultrasound were evaluated. CEUS was performed within one week before core needle biopsy or surgical resection and a revised BI-RADS classification was assigned based on 10 CEUS imaging characteristics. Receiver operating characteristic curve analysis was then conducted to evaluate the diagnostic performance of CEUS-based BI-RADS assignment with pathological examination as reference criteria. RESULTS: The CEUS-based BI-RADS evaluation classified 116/235 (49.36%) lesions into category 3, 20 (8.51%), 13 (5.53%) and 12 (5.11%) lesions into categories 4A, 4B and 4C, respectively, and 74 (31.49%) into category 5. Selecting CEUS-based BI-RADS category 4A as an appropriate cut off gave sensitivity and specificity values of 85.4% and 87.8%, respectively, for the diagnosis of malignant disease. The cancer-to-biopsy yield was 73.11% with CEUS-based BI-RADS 4A selected as the biopsy threshold compared with 40.85% otherwise, while the biopsy rate was only 42.13% compared with 100% otherwise. Overall, only 4.68% of invasive cancers were misdiagnosed. CONCLUSION: This pilot study suggests that evaluation of BI-RADS 4 breast lesions with CEUS results in reduced biopsy rates and increased cancer-to-biopsy yields. PMID- 27358690 TI - Assessment of sub-milli-sievert abdominal computed tomography with iterative reconstruction techniques of different vendors. AB - AIM: To assess diagnostic image quality of reduced dose (RD) abdominal computed tomography (CT) with 9 iterative reconstruction techniques (IRTs) from 4 different vendors to the standard of care (SD) CT. METHODS: In an Institutional Review Board approved study, 66 patients (mean age 60 +/- 13 years, 44 men, and 22 women) undergoing routine abdomen CT on multi-detector CT (MDCT) scanners from vendors A, B, and C (>= 64 row CT scanners) (22 patients each) gave written informed consent for acquisition of an additional RD CT series. Sinogram data of RD CT was reconstructed with two vendor-specific and a vendor-neutral IRTs (A-1, A-2, A-3; B-1, B-2, B-3; and C-1, C-2, C-3) and SD CT series with filtered back projection. Subjective image evaluation was performed by two radiologists for each SD and RD CT series blinded and independently. All RD CT series (198) were assessed first followed by SD CT series (66). Objective image noise was measured for SD and RD CT series. Data were analyzed by Wilcoxon signed rank, kappa, and analysis of variance tests. RESULTS: There were 13/50, 18/57 and 9/40 missed lesions (size 2-7 mm) on RD CT for vendor A, B, and C, respectively. Missed lesions includes liver cysts, kidney cysts and stone, gall stone, fatty liver, and pancreatitis. There were also 5, 4, and 4 pseudo lesions (size 2-3 mm) on RD CT for vendor A, B, and C, respectively. Lesions conspicuity was sufficient for clinical diagnostic performance for 6/24 (RD-A-1), 10/24 (RD-A-2), and 7/24 (RD-A 3) lesions for vendor A; 5/26 (RD-B-1), 6/26 (RD-B-2), and 7/26 (RD-B-3) lesions for vendor B; and 4/20 (RD-C-1) 6/20 (RD-C-2), and 10/20 (RD-C-3) lesions for vendor C (P = 0.9). Mean objective image noise in liver was significantly lower for RD A-1 compared to both RD A-2 and RD A-3 images (P < 0.001). Similarly, mean objective image noise lower for RD B-2 (compared to RD B-1, RD B-3) and RD C-3 (compared to RD C-1 and C-2) (P = 0.016). CONCLUSION: Regardless of IRTs and MDCT vendors, abdominal CT acquired at mean CT dose index volume 1.3 mGy is not sufficient to retain clinical diagnostic performance. PMID- 27358691 TI - Does therapist's attitude affect clinical outcome of lumbar facet joint injections? AB - AIM: To investigate if the clinical outcome of intra-articular lumbar facet joint injections is affected by the therapist's attitude. METHODS: A total of 40 patients with facet joint-associated chronic low back pain were randomly divided into two groups. All patients received computed tomography-guided, monosegmental intra-articular facet joint injections. Following the therapeutic procedure, the patients of the experimental group (EG) held a conversation with the radiologist in a comfortable atmosphere. During the dialog, the patients were encouraged to ask questions and were shown four images. The patients of the control group (CG) left the clinic without any further contact with the radiologist. Outcome was assessed using a pain-based Verbal Numeric Scale at baseline, at 1 wk and at 1, 3, and 6 mo after first treatment. RESULTS: The patient demographics showed no differences between the groups. The patients of the EG received 57 interventional procedures in total, while the patients of the CG received 70 interventional procedures. In both groups, the pain scores decreased significantly over the entire observation period. Compared to the CG, the EG showed a statistically significant reduction of pain at 1 wk and 1 mo post-treatment, while at 3 and 6 mo after treatment, there were no significant differences between both groups. CONCLUSION: Our results show a significant effect on pain relief during the early post-interventional period in the EG as compared to the CG. The basic principle behind the higher efficacy might be the phenomenon of hetero-suggestion. PMID- 27358693 TI - Alpha-fetoprotein and its value for predicting pregnancy outcomes - a re evaluation. AB - INTRODUCTION: Alpha-fetoprotein (AFP) concentrations can be determined framing others from invasively acquired amnion fluid (AF-AFP). While the biological role of AFP remains unclear it is well known that AFP-levels can be altered in connection with specific clinical and/or genetic alterations of the fetus. MATERIALS AND METHOD: here a retrospective study based on 3,119 singleton and 56 twin pregnancies is presented. The standard levels of amnion fluid derived alpha fetoprotein level (AF-AFP) between 12th and 36th weeks of gestation were determined. Additionally, acetylcholinesterase (AChE) test results for 63 cases, ultrasonography results for 32 cases and abnormal karyotypic findings for 100 cases were available for selected cases. RESULTS AND DISCUSSION: according to the present data the AF-AFP test is reliable and provides expected test results in terms of population studies. However, individual AF-AFP test results can be subject to high individual variations. In this study AF-AFP multiple of medians (MoM) over 1.7 were indicative for neuronal tube defects and/or omphalocele in only 6.3% of the cases, while such AF-AFP values were hints on severe sonographic signs in 62% of the cases. Also, altered AF-AFP concentrations were present in 82% of cytogenetically abnormal cases. Overall, even though predicative value of the AF-AFP-test is matter of discussion it continues to be widely applied in invasive prenatal diagnostics. This study indicates that it only can be applied reliably in combination with other tests like banding cytogenetics, ultrasonography and all embedded in well-established genetic counseling. PMID- 27358694 TI - First trimester fetal anatomy study and identification of major anomalies using 10 standardized scans. AB - OBJECTIVE: to validate the use of the first trimester scan not just as a screening tool for chromosomal anomalies, but also as a method to identify the major anatomic anomalies using 10 standardized scans. METHODS: five years of prospective study analyzing the fetal anatomy of 5924 patients with a singleton pregnancy during the first trimester screening for chromosomopathies. A check list of 10 predetermined scans had been used. The follow up consisted of two more scans in the second and third trimester, according to the local protocol, and a final evaluation of neonatal outcome at birth. RESULTS: in the 5924 examined patients, the percentage of major malformations is 0.74%, most of all discovered in the first trimester (47.7%). The Detection Rate for the malformations related to the nervous system is about 50% and for the malformations of the abdomen, heart and skeleton is slightly lower (43.5%). CONCLUSIONS: first trimester ultrasound using 10 standardized scans is a valid screening method for chromosomopathies and also an effective method to identify many of the major fetal anato - mical anomalies. PMID- 27358695 TI - Conservative management in a case of uncomplicated trap sequence: a case report and brief literature review. AB - INTRODUCTION: twin reversed arterial perfusion (TRAP) sequence is a rare anomaly that occurs in monochorionic twins with overall mortality rate ranging from 50% to 70% in the normal fetus, above all for congestive cardiac failure. CASE REPORT: a 31-year-old Caucasian gravida was referred to our fetomaternal medicine unit in the 25 gestational age. Ultrasound examination revealed a monochorionic, biamniotic twin pregnancy with a donor fetus showing normal morphology and growth corresponding to gestational age. The recipient twin appeared grossly abnormal with no head, upper limbs, heart, or thoracic structures and massive, diffuse, soft tissue edema. Fetal Doppler and fetal echocardiography revealed normal parameters. The patient refused any treatment and was monitored with weekly ultrasonography and Doppler ultrasound examination. She underwent cesarean section due to premature labor/rupture of membranes secondary to a mild polyhydramnios, at 36 weeks gestational age and delivered an apparent normal female live baby weighing 2550 gr, and another female acardius acephalus twin, birth weight 1300 gr. This baby had rudimental edematous lower limbs, pelvic bone, lower sacral vertebrae, and absence of thorax and cephalic structures. CONCLUSION: although the literature suggest that early intrafetal laser treatment of TRAP sequence is advantageous, our case shows that pregnancies referred late would still require a tailored approach after a risk-benefit assessment. PMID- 27358692 TI - Endocrine radionuclide scintigraphy with fusion single photon emission computed tomography/computed tomography. AB - AIM: To review the benefits of single photon emission computed tomography (SPECT)/computed tomography (CT) hybrid imaging for diagnosis of various endocrine disorders. METHODS: We performed MEDLINE and PubMed searches using the terms: "SPECT/CT"; "functional anatomic mapping"; "transmission emission tomography"; "parathyroid adenoma"; "thyroid cancer"; "neuroendocrine tumor"; "adrenal"; "pheochromocytoma"; "paraganglioma"; in order to identify relevant articles published in English during the years 2003 to 2015. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved manuscripts (case reports, reviews, meta-analyses and abstracts) concerning the application of SPECT/CT to endocrine imaging were analyzed to provide a descriptive synthesis of the utility of this technology. RESULTS: The emergence of hybrid SPECT/CT camera technology now allows simultaneous acquisition of combined multi-modality imaging, with seamless fusion of three-dimensional volume datasets. The usefulness of combining functional information to depict the bio distribution of radiotracers that map cellular processes of the endocrine system and tumors of endocrine origin, with anatomy derived from CT, has improved the diagnostic capability of scintigraphy for a range of disorders of endocrine gland function. The literature describes benefits of SPECT/CT for (99m)Tc-sestamibi parathyroid scintigraphy and (99m)Tc-pertechnetate thyroid scintigraphy, (123)I- or (131)I-radioiodine for staging of differentiated thyroid carcinoma, (111)In- and (99m)Tc- labeled somatostatin receptor analogues for detection of neuroendocrine tumors, (131)I-norcholesterol (NP-59) scans for assessment of adrenal cortical hyperfunction, and (123)I- or (131)I-metaiodobenzylguanidine imaging for evaluation of pheochromocytoma and paraganglioma. CONCLUSION: SPECT/CT exploits the synergism between the functional information from radiopharmaceutical imaging and anatomy from CT, translating to improved diagnostic accuracy and meaningful impact on patient care. PMID- 27358696 TI - Evaluation of Carotid Plaque Using Ultrasound Imaging. AB - Traditional risk factors for predicting of cardiovascular disease are not always effective predictors for development of cardiovascular events. This review summarizes several newly developed noninvasive imaging techniques for evaluating carotid plaques and their role in cardiovascular disease risk. PMID- 27358697 TI - The Use of Cardiac Magnetic Resonance in Patients with Suspected Coronary Artery Disease: A Clinical Practice Perspective. AB - Cardiac magnetic resonance imaging (CMR) is a useful diagnostic imaging modality in patients with known or suspected coronary artery disease (CAD). It provides unique information not available from other modalities, however, it is complex. CMR is not a single technique. Instead, it consists of multiple distinct techniques and a lack of understanding of which techniques to perform and how to interpret the findings in combination limits its efficacy and widespread use. Conversely, its multiparametric nature can provide a comprehensive assessment with the potential for higher accuracy than is achievable by other modalities. Moreover, its ability to directly assess myopathic processes often contributes insights that change patient management. In this article we provide a brief technical overview and focus on specific clinical scenarios in patients with known or suspected CAD. We highlight the multiparametric nature of CMR and discuss cases which illustrate the unique information that CMR can contribute. PMID- 27358699 TI - An Optimistic View towards the Real Time 3D Echocardiography in Congenital Heart Disease: A Simple 'Crop Box' Should Give an Infinite Information in the Near Future! PMID- 27358698 TI - Neutrophil-to-Lymphocyte Ratio for Risk Assessment in Coronary Artery Disease and Carotid Artery Atherosclerosis. PMID- 27358700 TI - Prognostic Implication of Strain Analysis in Patients with ST-Segment Elevation Myocardial Infarction: One More Evidence for Ever-Debatable Topic. PMID- 27358701 TI - Is Needed Dobutamine Stress Echocardiography for the Detection of Coronary Artery Stenosis in Women? PMID- 27358702 TI - Normal Reference Values for Doppler Echocardiography: Influences of Ageing, Gender and Ethnicity. PMID- 27358703 TI - The Combined Impact of Neutrophil-to-Lymphocyte Ratio and Type 2 Diabetic Mellitus on Significant Coronary Artery Disease and Carotid Artery Atherosclerosis. AB - BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as a new important inflammatory marker for predicting cardiovascular events. This study aimed to evaluate the combined impact of NLR and type 2 diabetes mellitus (T2DM) on significant coronary artery disease (CAD) and carotid artery atherosclerosis. METHODS: This study includes a total of 828 patients evaluated by coronary angiography and carotid ultrasonography. Significant CAD was defined as at least one vessel with stenosis greater than 50%. We employed logistic regression models to investigate the association of NLR and T2DM with significant CAD. The goodness of-fit and discriminability of the models were assessed by the loglikelihood ratio test and C-index, respectively. Also, we investigated the clinical relevance of the categorized NLR that classifies patients into three risk groups (low, intermediate, high). RESULTS: According to logistic regression analysis, both NLR {adjusted odds ratio (OR) 1.31, p < 0.001} and T2DM (adjusted OR 2.46, p = 0.006) were independent risk factors of significant CAD. The addition of NLR and T2DM into a logistic regression model including conventional cardiovascular risk factors significantly improved the goodness-of-fit (p < 0.001) and the discriminability of the model (p = 0.004). Also, T2DM patients assigned into the high risk group (NLR > 2) showed the greater prevalence of significant CAD and carotid artery atherosclerosis compared with patients without T2DM or type 2 diabetic patients assigned into the low risk group (NLR <= 1). CONCLUSION: Our results suggest that type 2 diabetic patients with high inflammatory state would be more vulnerable to significant CAD and carotid artery atherosclerosis. PMID- 27358704 TI - Assessment of Left Ventricular Volume and Function Using Real-Time 3D Echocardiography versus Angiocardiography in Children with Tetralogy of Fallot. AB - BACKGROUND: Evaluation of left ventricular (LV) size and function is one of the important reasons for performing echocardiography. Real time three dimensional echocardiography (RT3DE) is now available for a precise non-invasive ventricular volumetry. Aim of work was to validate RT3DE as a non-invasive cardiac imaging method for measurement of LV volumes using cardiac angiography as the reference technique. METHODS: Prospective study on 40 consecutive patients with tetralogy of Fallot (TOF) referred for cardiac catheterization for preoperative assessment. Biplane cineangiography, conventional 2 dimensional echocardiography (2DE) and RT3DE were performed for the patients. A control group of 18 age and sex matched children was included and 2DE and RT3DE were performed for them. RESULTS: The mean LV end diastolic volume (LVEDV) and LVEDV index (LVEDVI) measured by RT3DE of patients were lower than controls (p value = 0.004, 0.01, respectively). There was strong correlation between the mean value of the LVEDV and the LVEDVI measured by RT3DE and angiography (r = 0.97, p < 0.001). The mean value of LV ejection fraction measured by RT3DE was lower than that assessed by 2DE (50 +/- 6.2%, 65 +/- 4.6%, respectively, p value < 0.001) in the studied TOF cases. There was good intra- and inter-observer reliability for all measurements. CONCLUSION: RT3DE is a noninvasive and feasible tool for measurement of LV volumes that strongly correlates with LV volumetry done by angiography in very young infants and children, and further studies needed. PMID- 27358705 TI - Echocardiographic Predictors for Left Ventricular Remodeling after Acute ST Elevation Myocardial Infarction with Low Risk Group: Speckle Tracking Analysis. AB - BACKGROUND: We sought to assess echocardiographic predictors of left ventricular (LV) adverse remodeling after successfully reperfused acute ST elevation myocardial infarction (STEMI). LV remodeling is commonly found in STEMI patients and it may suggest adverse outcome in acute myocardial infarction. We sought to identify whether 2D strain and torsion be independent parameters for prediction of LV adverse remodeling. METHODS: We investigated 208 patients with low-risk STEMI patients who had follow up echocardiography at 6 or more months. After clinical assessments, all patients received revascularization according to current guideline. LV remodeling was defined as > 20% increase in end-diastolic volume (EDV) at follow up. RESULTS: During the follow-up (11.9 +/- 5.3 months), 53 patients (25.5%) showed LV remodeling. In univariate analysis, EDV, end systolic volume, deceleration time (DT), CK-MB, and global longitudinal strain (GLS) were associated with LV remodeling. In multivariate analysis, EDV [hazard ratio (HR): 0.922, 95% confidence interval (CI): 0.897-0.948, p< 0.001], GLS (HR: 0.842, 95% CI: 0.728-0.974, p = 0.020), DT (HR: 0.989, 95% CI: 0.980-0.998, p = 0.023) and CK-MB (HR: 1.003, 95% CI: 1.000-1.005, p = 0.033) independently predicted LV remodeling. However, global circumferential strain, net twist, and twist or untwist rate were not associated with remodeling. CONCLUSION: Of various parameters of speckle strain, only GLS predicted adverse remodeling in STEMI patients. PMID- 27358706 TI - Head to Head Comparison of Stress Echocardiography with Exercise Electrocardiography for the Detection of Coronary Artery Stenosis in Women. AB - BACKGROUND: Exercise-stress electrocardiography (ECG) is initially recommended for the diagnosis of coronary artery disease. But its value has been questioned in women because of suboptimal diagnostic accuracy. Stress echocardiography had been reported to have comparable test accuracy in women. But the data comparing the diagnostic accuracy of exercise-stress ECG and stress echocardiography directly are few. The aim of the study was to compare the diagnostic accuracy of exercise-stress ECG and dobutamine stress echocardiography (DSE) in Korean women. METHODS: 202 consecutive female patients who presented with chest pain in outpatient clinic, and who underwent treadmill exercise test (TET), DSE and coronary angiography were included for the study. The diagnostic accuracy TET and DSE were calculated by the definition of > 50% or > 75% coronary artery stenosis (CAS). RESULTS: The sensitivity and specificity were higher with DSE (70.4, 94.6%) than TET (53.7, 73.6%) for detection of > 50% CAS. The higher accuracy of DSE was maintained after exclusion of the patients who could not achieve over 85% age predicted heart rate before ischemia induction. DSE also showed greater diagnostic accuracy than TET by > 75% CAS criteria, and in subsets of patient with intermediate pretest probability. CONCLUSION: In the diagnosis of CAS, DSE showed higher accuracy than TET in female patients who presented with chest pain. As well as the test accuracy, adequate stress was more feasible with DSE than TET. These finding suggests DSE may be used as the first-line diagnostic tool in the detection of CAS in women with chest pain. PMID- 27358708 TI - Identification of a Novel De Novo Mutation of the TAZ Gene in a Korean Patient with Barth Syndrome. AB - Barth syndrome (BTHS) is a rare genetic disorder characterized by various types of cardiomyopathy, neutropenia, failure to thrive, skeletal myopathy, and 3 methylglutaconic aciduria. BTHS is caused by loss-of-function mutations in the tafazzin (TAZ) gene located on chromosome Xq28, leading to cardiolipin deficiency. We report a 13-month-old boy with BTHS who had a novel de novo mutation in the TAZ gene. To the best of our knowledge, this is the first reported case of a BTHS patient with a de novo mutation in Korea. This report will contribute towards expanding the knowledge on the mutation spectrum of the TAZ gene in BTHS. PMID- 27358709 TI - Pregnancy in Hypertrophic Cardiomyopathy with Severe Left Ventricular Outflow Tract Obstruction. AB - Hypertrophic obstructive cardiomyopathy (HOCM) patients with severe left ventricular outflow tract (LVOT) obstruction (those with a gradient of > 100 mm Hg) are at the highest risk of hemodynamic deterioration during pregnancy. Complications of HOCM include sudden cardiac death, heart failure, and arrhythmias. Physiological changes during pregnancy may induce these complications, affecting maternal and fetal health conditions. Therefore, close monitoring with appropriate management is essential for the well-being of both mother and fetus. We report on the case of a 27-year-old female patient with severe LVOT obstruction HOCM, pressure gradient (PG) of 125 mm Hg at resting, and 152 mm Hg induced by the Valsalva maneuver at 34 weeks gestation. This case showed how close monitoring using echocardiography and proper management during the course of pregnancy resulted in successful delivery in the patient with extremely high PG HOCM. PMID- 27358710 TI - Successfully Treated Acute Fulminant Myocarditis Induced by Ulcerative Colitis with Extracorporeal Life Support and Infliximab. AB - We report a case of successfully treated acute fulminant myocarditis induced by ulcerative colitis with extracorporeal life support and infliximab. Myocarditis is a rare but crucial complication during an exacerbation of inflammatory bowel disease. In our case, we applied extracorporeal membrane oxygenation (ECMO) for cardiac rest under impression of acute myocarditis associated with ulcerative colitis, and added infliximab for uncontrolled inflammation by corticosteroid. As a result, our patient was completely recovered with successful weaning of ECMO. PMID- 27358707 TI - Normal Echocardiographic Measurements in a Korean Population Study: Part II. Doppler and Tissue Doppler Imaging. AB - BACKGROUND: Hemodynamic and functional evaluation with Doppler and tissue Doppler study as a part of comprehensive echocardiography is essential but normal reference values have never been reported from Korean normal population especially according to age and sex. METHODS: Using Normal echOcaRdiographic Measurements in a KoreAn popuLation study subjects, we obtained normal reference values for Doppler and tissue Doppler echocardiography including tricuspid annular velocities according to current guidelines and compared values according to gender and age groups. RESULTS: Mitral early diastolic (E) and late diastolic (A) velocity as well as E/A ratio were significantly higher in women compared to those in men. Conversely, mitral peak systolic and late diastolic annular velocity in both septal and lateral mitral annulus were significantly lower in women compared to those in men. However, there were no significant differences in both septal and lateral mitral early diastolic annular (e') velocity between men and women. In both men and women, mitral E velocity and its deceleration time as well as both E/A and E/e' ratio considerably increased with age. There were no significant differences in tricuspid inflow velocities and tricuspid lateral annular velocities between men and women except e' velocity, which was significantly higher in women compared to that in men. However, changes in both tricuspid inflow and lateral annular velocities according to age were similar to those in mitral velocities. CONCLUSION: Since there were significant differences in Doppler and tissue Doppler echocardiographic variables between men and women and changes according to age were even more considerable in both gender groups, normal Doppler echocardiographic values should be differentially applied based on age and sex. PMID- 27358711 TI - Rare Case of Unileaflet Mitral Valve. AB - Unileaflet mitral valve is the rarest of the congenital mitral valve anomalies and is usually life threatening in infancy due to severe mitral regurgitation (MR). In most asymptomatic individuals, it is mostly due to hypoplastic posterior mitral leaflet. We present a 22-year-old male with palpitations, who was found to have an echocardiogram revealing an elongated anterior mitral valve leaflet with severely hypoplastic posterior mitral valve leaflet appearing as a unileaflet mitral valve without MR. Our case is one of the 11 reported cases in the literature so far. We hereby review those cases and conclude that these patients are likely to be at risk of developing worsening MR later in their lives. PMID- 27358712 TI - A Rare Case of Lipomatous Hypertrophy of the Interventricular Septum. AB - Asymmetrical left ventricular hypertrophy secondary to interventricular septum hypertrophy is usually considered a typical phenotype of hypertrophic cardiomyopathy. In rare cases other conditions such as tumors or lipomatous hypertrophy of the interventricular septum may have a similar presentation. We present a case of a male patient who presented for routine cardiology work up and was diagnosed of having ventricular septal hypertrophy secondary to localized lipomatous hypertrophy. PMID- 27358713 TI - A Left Atrial Appendage Phantom Structure. PMID- 27358714 TI - Acute Myeloid Leukemia with Intracardiac Thrombus Presenting as Acute Limb Ischemia. PMID- 27358715 TI - Image Diagnosis: Pericardial Cyst in a Dialysis Patient. PMID- 27358716 TI - Response to Letter Regarding Article, "Stress-Induced Cardiomyopathy Presenting as Shock". PMID- 27358717 TI - Circulating biomarkers to monitor cancer progression and treatment. AB - Tumor heterogeneity is a major challenge and the root cause of resistance to treatment. Still, the standard diagnostic approach relies on the analysis of a single tumor sample from a local or metastatic site that is obtained at a given time point. Due to intratumoral heterogeneity and selection of subpopulations in diverse lesions this will provide only a limited characterization of the makeup of the disease. On the other hand, recent developments of nucleic acid sequence analysis allows to use minimally invasive serial blood samples to assess the mutational status and altered gene expression patterns for real time monitoring in individual patients. Here, we focus on cell-free circulating tumor-specific mutant DNA and RNA (including mRNA and non-coding RNA), as well as current limitations and challenges associated with circulating nucleic acids biomarkers. PMID- 27358718 TI - MicroRNAs and oncogenic transcriptional regulatory networks controlling metabolic reprogramming in cancers. AB - Altered cellular metabolism is a fundamental adaptation of cancer during rapid proliferation as a result of growth factor overstimulation. We review different pathways involving metabolic alterations in cancers including aerobic glycolysis, pentose phosphate pathway, de novo fatty acid synthesis, and serine and glycine metabolism. Although oncoproteins, c-MYC, HIF1alpha and p53 are the major drivers of this metabolic reprogramming, post-transcriptional regulation by microRNAs (miR) also plays an important role in finely adjusting the requirement of the key metabolic enzymes underlying this metabolic reprogramming. We also combine the literature data on the miRNAs that potentially regulate 40 metabolic enzymes responsible for metabolic reprogramming in cancers, with additional miRs from computational prediction. Our analyses show that: (1) a metabolic enzyme is frequently regulated by multiple miRs, (2) confidence scores from prediction algorithms might be useful to help narrow down functional miR-mRNA interaction, which might be worth further experimental validation. By combining known and predicted interactions of oncogenic transcription factors (TFs) (c-MYC, HIF1alpha and p53), sterol regulatory element binding protein 1 (SREBP1), 40 metabolic enzymes, and regulatory miRs we have established one of the first reference maps for miRs and oncogenic TFs that regulate metabolic reprogramming in cancers. The combined network shows that glycolytic enzymes are linked to miRs via p53, c-MYC, HIF1alpha, whereas the genes in serine, glycine and one carbon metabolism are regulated via the c-MYC, as well as other regulatory organization that cannot be observed by investigating individual miRs, TFs, and target genes. PMID- 27358719 TI - Commentary: sex difference differences? A reply to Constantino. AB - Messinger et al. found a 3.18 odds ratio of male to female ASD recurrence in 1241 prospectively followed high-risk (HR) siblings. Among high-risk siblings (with and without ASD), as well as among 583 low-risk controls, girls exhibited higher performance on the Mullen Scales of Early Learning, as well as lower restricted and repetitive behavior severity scores on the Autism Diagnostic Observation Schedule (ADOS) than boys. That is, female-favoring sex differences in developmental performance and autism traits were evident among low-risk and non ASD high-risk children, as well as those with ASD. Constantino (Mol Autism) suggests that sex differences in categorical ASD outcomes in Messinger et al. should be understood as a female protective effect. We are receptive to Constantino's (Mol Autism) suggestion, and propose that quantitative sex differences in autism-related features are keys to understanding this female protective effect. PMID- 27358720 TI - Data from the Baby Siblings Research Consortium confirm and specify the nature of the female protective effect in autism: A commentary on Messinger et al. AB - Sibling recurrence data from the Baby Siblings Research Consortium (BSRC) recapitulate results from very large clinical family studies that demonstrate the absence of the Carter effect and provide clarification of the nature of the female protective effect in ASD. This legacy prospective data collection confirmed marked differences in the proportions of males versus females who lie along deviant trajectories of social development in the setting of inherited liability to autism--a phenomenon which defines the female protective effect--and demonstrate that among affected children, sex differences are modest and homologous to those observed among non-ASD children. PMID- 27358722 TI - Commentary on a smoke-free medical campus in Jerusalem: data for action. AB - Over the past 30 years, Israel has made great progress in attitudes and practices about smoking; probably nothing else has contributed more to the health of its population. Yet, a recent survey about a non-smoking ban at an Israeli health sciences campus found incomplete enforcement. In addition, smoking rates among health sciences students, though lower than the general population, were higher than might be expected based on rates in other developed countries. Whether the ban is-as the authors speculate-"an intrusive life style intervention" or a justifiable public health intervention, cuts to the heart of the history of tobacco control efforts and their opposition by the tobacco industry. Despite concerns that the Israeli population is not ready to accept smoke-free bans, experience in other countries suggests otherwise. PMID- 27358721 TI - Phosphorylated-insulin growth factor I receptor (p-IGF1R) and metalloproteinase-3 (MMP3) expression in advanced gastrointestinal stromal tumors (GIST). A GEIS 19 study. AB - BACKGROUND: Most GISTs have mutations in KIT or PDGFRA. Patients with advanced GIST with KIT exon 9, PDGFRA mutation or WT for KIT and PDGFRA have a worse progression-free survival (PFS) compared to patients with KIT exon 11 mutated tumors. We evaluated the immunohistochemical (IHC) expression of p-IGF1R (Y1316) and MMP3 as predictors of PFS or overall survival (OS). METHODS: Ninety-two advanced GIST patients included in GEIS-16 study with KIT and PDGFRA mutational information were examined for p-IGF1R (Y1316) and MMP3 expression in a tissue micro-array. To study activation of the IGF1R system, we have used an antibody (anti-pY1316) that specifically recognizes the active phosphorylated form of the IGF1R. DNA was extracted from paraffin-embedded tissues and intronic PCR primers were used to amplify exons 9, 11, 13 and 17 of KIT, 12 and 18 of PDGFRA. Bidirectional sequencing with specific primers was performed on a ABI3100 sequencer using the Big Dye Terminator v3.1 kit. Multivariate model was built using a stepwise automated variable selection approach with criterion to enter the variable in the model of p < 0.10 and criterion to keep the variable in the model of p < 0.05. PFS was computed as the date of imatinib initiation to progression or death. Overall survival was defined as the time from imatinib initiation to death. RESULTS: Phospho-IGF1R was expressed only in 9 % (2/22) of cases without KIT mutation. MMP3 expression was detected in 2/5 patients (40 %) with PDGFRA mutation, 1/16 patients (6 %) with WT genotype and 7/71 patients (10 %) of KIT mutant patients. At univariate analysis KIT exon 11/13 mutation had better PFS than patients with exon 9 mutation, PDGFRA mutation or WT genotype (p = 0.021; HR: 0.46; 95 %CI (0.28-0.76). Less than 24 months disease free-interval (HR 24.2, 95 % CI 10.5-55.8), poor performance status (PS) (HR 6.3, 95 % CI 2.5 15.9), extension of disease; >1 organ (HR 1.89; 95 % CI 1.03-3.4) and genotype analysis (HR 0.57, 95 % CI 0.37-0.97) but not immunophenotype analysis (HR 1.53; 95 % CI 0.76-3.06) were the strongest prognostic factors for PFS in the multivariate analysis. CONCLUSIONS: Our results do not support p-IGF-1R and MMP3 evaluation in non-selected GIST patients but evaluation of this immunophenotype in WT and mutant PDGFR mutation in larger group of GIST patients, deserve merits. PMID- 27358723 TI - Physician-facilitated designation of proxy decision maker. AB - With vast improvements in healthcare in recent decades, people are living longer but often with higher rates of morbidity and chronic illnesses. This has resulted in a higher proportion of the population who may benefit from early end-of-life 'conversation and planning', but also gives healthcare professionals more time during which these discussions are relevant, as people live longer with their chronic diseases. A survey conducted by Lifshitz et al (Isr J Health Policy Res 5:6, 2016) sought to assess physician awareness and willingness to discuss designating a proxy decision-maker with patients, in order to aid end-of-life care in the event that the patient is rendered unable to make or communicate these decisions later in life. Their article suggests that proxy decision-maker designation is only one aspect of end-of-life care; a challenging area littered with ethical and moral dilemmas. Without early, open and frank discussions with patients regarding their wishes at the end of life, proxy decision-makers may be in no better position than physicians or a court appointed proxy to make decisions in the patients' best interests/benefits. This commentary also touches upon the use of health and care passports being developed or in early phases in the United Kingdom, and whether these may be utilised in the field of palliative care in Israel. PMID- 27358724 TI - Pre-exercise screening: role of the primary care physician. AB - Participation in regular physical activity is associated with a multitude of benefits including a reduction in chronic disease and premature mortality, and improved quality of life. All segments of society need to collaborate with one another in an effort to promote active lives. The Israeli "Gymnasium Law" requires pre-exercise evaluation prior to exercise participation in a health club. Recently that law was modified to allow for participant pre-screening with the Physical Activity Readiness Questionnaire for Everyone (PAR-Q+). This change reflects the evidence that the risk of catastrophic events (e.g. heart attack) during moderate intensity physical activity is low, and the likelihood of detecting heart disease in asymptomatic adults is low. This change will likely reduce the number of individuals who require physician evaluation. The American College of Sports Medicine (ACSM) recently updated their recommendations for pre exercise evaluation. The ACSM guidelines have replaced risk factor assessment, with an algorithm that first stratifies based on current physical activity level, then by the presence of chronic disease, and/or signs and symptoms of chronic disease, and last by desired exercise intensity. The goal of these efforts is to reduce barriers to regular physical activity, by eliminating unnecessary medical evaluations. All adults should be encouraged to be physically active. PMID- 27358725 TI - Decision-makers' acquaintance with the public's priorities in health services. AB - BACKGROUND: Decision makers often assume they know the public's standpoints and see themselves as capable of representing them. The aim of this study is to assess the level of acquaintance that senior decision-makers in the Israeli health system have concerning the priorities of the public in whose name they act. METHODS: A phone survey was conducted with a representative population sample and face-to-face interviews were conducted with senior decision-makers. RESULTS: The decision-makers did predict correctly the public's desired level of government involvement in health care; but only some of them correctly predicted the public's preferences on allocation of funds-to health versus other areas. They had difficulty foreseeing public priorities for allocating additional monies to health, and even greater difficulty ascertaining preferences of the public for their own health insurance. CONCLUSIONS: Government decision-making processes should include evidence about public preferences. The findings of this study indicate that decision makers need to be provided with reliable, systematic information on public preferences. PMID- 27358727 TI - Left upper lobe double sleeve lobectomy with double barrel anastomosis for lung adenocarcinoma. AB - INTRODUCTION: Bronchoplasty is performed for both curability and preservation of the pulmonary function. CASE PRESENTATION: We herein report the findings of a 65 year old female patient who was admitted to our hospital to undergo surgical treatment for lung cancer. We successfully performed left upper lobe double sleeve lobectomy and reconstructed the site through bronchoplasty with double barrel (B6 + basal bronchus) anastomosis using inner ligation in a given location. DISCUSSION: The postoperative course was uneventful, and full-dose adjuvant chemotherapy was performed. No stenosis or narrowing of the airways was recognized. Chest CT also showed a good expansion of the residual lung, and the pulmonary function was also reserved. CONCLUSION: We propose the use of inner ligation in double barrel bronchoplasty at a particular site. PMID- 27358726 TI - Influence of profilin on sensitisation profiles determined by cutaneous tests and IgE to major allergens in polysensitised patients. AB - BACKGROUND: Profilin sensitisation is considered a diagnostic confounding factor in areas where patients are exposed to multiple pollens. The aim of this study is to assess pollen sensitisation profiles in adults and children and to evaluate, by means of component-resolved diagnosis (CRD) and skin prick testing (SPT), which pollens may be considered as risk factors of profilin sensitisation in order to establish the best diagnostic approach in polysensitised patients. METHODS: A total of 231 pollen-allergic patients (adults and children) were included, out of the pollen season, from an area with similar levels of pollen exposure. Allergological diagnosis was performed by SPT and determination of specific IgE (sIgE) to major allergen components (ADVIA-CentaurTM). Patients had not received immunotherapy in the last 5 years and had to reside in the area for 5 consecutive years before entering the study. RESULTS: The relation between sensitisation measured by SPT and by sIgE was studied using a model of cases (patients with +sIgE to a specific allergen) and controls (patients with -sIgE to the same allergen). The outcome, in terms of odds-ratios (OR), was statistically significant for Olea (Ole e 1) (p = 0.0005), Salsola (Sal k 1) (p = 0.0118) and Platanus (Pla a 1+ 2) (p = 0.0372). While positivity of SPT to most pollens was statistically associated with a risk of profilin sensitisation, by CRD the association was statistically significant only for Ole e 1 (OR 3.5, CI 95 %, 1.6 7.6, p = 0.0014), and Phl p 5 (OR 11.9, CI 95 %, 4.1-35.2, p < 0.001). When analysing this association using a logistic regression model, Phl p 5 was the only allergen associated with the risk of being sensitised to profilin (p = 0.0023). CONCLUSIONS: In patients sensitised to profilin, the concordance between SPT and CRD is much lower than in those not sensitised to profilin. CRD is able to provide refined information about which pollens increase the risk of sensitisation to profilin. PMID- 27358728 TI - Achieving long term survival in oesophagectomy patients aged over 75. AB - AIMS: Surgical resection is often the only curative treatment for oesophageal cancer. The aim of this retrospective cohort study was to analyse outcomes following oesophageal resection in patients aged 75 years and older and the impact of an Enhanced Recovery after Surgery (ERAS) program in this cohort. METHODS: Patients aged over 75 years undergoing oesophagectomy between 2003 and 2013 were identified from a single centre using an electronic database. Data on pre-operative comorbidity, tumour stage and length of hospital stay (LOS) were collected. Complications were classified according to the Clavien-Dindo system. Thirty day, 1- and 5-year mortality rates were calculated. RESULTS: 147 patients were identified with a median age of 78.5 (IQR 76.7-80.9). 33% (n = 44) had a grade 3 complication or higher. Median LOS in hospital was 16 days (IQR 13.0 22.0). Thirty-day mortality was 3.4%, 1-year and 5-year survival was 65% and 21% respectively. 45% of patients were enrolled into an Enhanced Recovery After Surgery program and they demonstrated a significantly reduced length of stay from 18 to 14 days (p = 0.005) and 30-day mortality from 6.2% to 0% (p = 0.04) compared to the time period before the program. CONCLUSION: Long-term survival is achievable in patients aged over 75 years. PMID- 27358730 TI - Burnout among surgical residents in a lower-middle income country - Are we any different? AB - OBJECTIVE: To assess the presence of burnout among surgical residents working at various public sector hospitals in Pakistan. DESIGN: A survey based on MBI was used to assess the presence of burnout. Residents were grouped into Group A (Burn out) or Group B (No burn out). Pearson Test was used to see any correlation between different variables and burn out. A p value of <0.05 was taken as significant. SETTING/PARTICIPANTS: A cross sectional survey of all the surgical residents at various public sector hospitals in Lahore was done. RESULTS: A total of 133 residents responded to our questionnaire. 74% respondents were male and 26% were female. All residents showed a very high level of burnout. 50.4% residents had high levels of burn out on the EE category, 49.6% in the DP category and 53.4% residents had low levels on the PA scale. When assessed for overall burn out 57.9% residents had overall burnout. Males were more prone to develop burnout. Job dissatisfaction was the most prevalent reason for burn out. Owning a smartphone was significantly associated with development of burnout. Awareness regarding the burnout syndrome and having children were two factors which had a protective effect against burnout syndrome. Marriage, working hours, financial conditions, smoking and consumption of coffee/tea had no effect on development of burnout syndrome. CONCLUSION: There is high prevalence of burnout among the surgical residents in our hospitals. Unsatisfactory training is the number one reason for development of this syndrome. PMID- 27358729 TI - Arginine dimethylation products in pediatric patients with chronic kidney disease. AB - BACKGROUND: arginine and its metabolites have been linked to pediatric chronic kidney disease (CKD). We aimed to estimate serum levels of argninine (Arg), asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) in pediatric CKD patients and its relation to altered kidney function. PATIENTS AND METHODS: 132 pediatric patients with CKD and 120 healthy age and sex matched controls were compared regarding; serum Arg, ADMA and SDMA levels. RESULTS: In comparison to their values in control subjects, serum Arg levels were significantly lower; serum ADMA levels were non-significantly higher, but serum SDMA levels were significantly higher in CKD patients (p values: < 0.000; = 0.054; <0.000, respectively). Calculated Arg/ADMA and Arg/SDMA ratios were significantly higher in patients compared to controls (p values: 0.001, and <0.000, respectively). However ADMA/SDMA ratio was significantly lower in patients compared to controls (p = 0.001. Serum Arg levels showed positive significant correlation, while serum ADMA and SDMA levels showed negative significant correlation with eGFR. Moreover, Arg/ADMA ratio showed negative significant correlation, while ADMA/SDMA ratio showed positive significant correlation with eGFR of patients. Regression analysis defined high serum SDMA level as persistently significant predictor for low eGFR. CONCLUSION: Disturbed serum levels of arginine and its dimethyl derivatives may underlie development and/or progression of CKD. Elevated serum SDMA level is strongly correlated with impaired kidney functions and could be considered as a predictor for kidney functions deterioration and CKD progression. PMID- 27358731 TI - Association between pregnancy exposure to air pollution and birth weight in selected areas of Norway. AB - BACKGROUND: Exposure to air pollution has adverse effects on cardiopulmonary health of adults. Exposure to air pollution in pregnancy may affect foetal development. However, the evidence of such effect remains inconsistent. We investigated the effects of exposure to air pollution during pregnancy on birth outcomes. METHODS: This study, based within the Norwegian Mother and Child Cohort Study (MoBa), includes 17,533 participants living in the two largest cities in Norway: Oslo and Bergen, and their two surrounding counties: Akershus and Hordaland. Air pollution levels at residential addresses were estimated using land use regression models and back-extrapolated to the period of each pregnancy using continuous monitoring station data. Birth outcomes were birth weight, low birth weight, gestational age, and preterm delivery obtained from the Medical Birth Registry of Norway. Information on lifestyle factors was collected from MoBa questionnaires completed by mothers during pregnancy. Linear and logistic regression models were used to analyse the associations between pregnancy NO2 exposure and birth outcomes. RESULTS: We found a statistically significant negative association between pregnancy exposure to NO2 and birth weight -43.6 (95%CI -55.8 to -31.5) g per 10 MUg/m(3) NO2. However, after adjusting for either area or the combination of parity and maternal weight, no substantive effects of air pollution exposure were evident. CONCLUSIONS: Exposure to air pollution during pregnancy was associated with decrease in birth weight, but area-related and lifestyle factors attenuated this association. We found no statistically significant associations of air pollution exposure with gestational age, low birth weight or preterm delivery. PMID- 27358732 TI - Sarcoidosis with prevalent and severe joint localization: a case report. AB - BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown origin, characterized by the formation of granulomas without central necrosis. Each organ and tissue can be affected by the disease, but in most cases mainly the lungs and mediastinal lymph nodes but also skin, heart, eyes and joints are involved, the latter are mainly the metacarpophalangeal joints and bone lesions are often associated with involvement of the overlying skin. The diagnosis is often of exclusion, based on clinical and radiological suspicion, and should be confirmed by biopsy, although in each case it is necessary to exclude other possible causes of granulomatosis, including infections by mycobacteria. Here it is reported a case of particularly aggressive sarcoidosis with primitive involvement of the small joints of the hands and feet, and mediastinal lymph nodes. CASE PRESENTATION: The subject, a man, 60 years old, born in Morocco but living in Italy for many years, presented important involvement of bone structures and soft periarticular tissue, and was affected by the formation of granulomas without "caseum necrosis". The painful symptoms and the skin ulceration had led to surgical amputation of the distal phalanges of most fingers of his hands and feet, but with subsequent resurgence of lesions in acral locations after surgery. The PET/CT scan showed an amount of radiotracer in mediastinal lymph nodes, while the lymph nodes sampled by TBNA were normal and the CD4/CD8 ratio was less than 3 in the bronchoalveolar lavage. We ruled out any possible infectious cause, including mycobacterial infection (both tubercular and atypical), so the patient was treated with systemic corticosteroids, with an excellent clinical and radiological response. CONCLUSIONS: Such a case shows how the disease can have variable expressions, without primitive lung involvement; therefore, it should be necessary to consider any possible, unpredictable localization of the disease. PMID- 27358733 TI - Efficient suppression of back electron/hole recombination in cobalt phosphate surface-modified undoped bismuth vanadate photoanodes. AB - In this paper, we compared for the first time the dynamics of photogenerated holes in BiVO4 photoanodes with and without CoPi surface modification, employing transient absorption and photocurrent measurements on microsecond to second timescales. CoPi surface modification is known to cathodically shift the water oxidation onset potential; however, the reason for this improvement has not until now been fully understood. The transient absorption and photocurrent data were analyzed using a simple kinetic model, which allows quantification of the competition between electron/hole recombination and water oxidation. The results of this model are shown to be in excellent agreement with the measured photocurrent data. We demonstrate that the origin of the improvement of photocurrent onset resulting from CoPi treatment is primarily due to retardation of back electron/hole recombination across the space charge layer; no evidence of catalytic water oxidation via CoPi was observed. PMID- 27358734 TI - Crystal structure and proton conductivity of BaSn0.6Sc0.4O3-delta : insights from neutron powder diffraction and solid-state NMR spectroscopy. AB - The solid-state synthesis and structural characterisation of perovskite BaSn1-x Sc x O3-delta (x = 0.0, 0.1, 0.2, 0.3, 0.4) and its corresponding hydrated ceramics are reported. Powder and neutron X-ray diffractions reveal the presence of cubic perovskites (space group Pm3m) with an increasing cell parameter as a function of scandium concentration along with some indication of phase segregation. 119Sn and 45Sc solid-state NMR spectroscopy data highlight the existence of oxygen vacancies in the dry materials, and their filling upon hydrothermal treatment with D2O. It also indicates that the Sn4+ and Sc3+ local distribution at the B-site of the perovskite is inhomogeneous and suggests that the oxygen vacancies are located in the scandium dopant coordination shell at low concentrations (x <= 0.2) and in the tin coordination shell at high concentrations (x >= 0.3). 17O NMR spectra on 17O enriched BaSn1-x Sc x O3-delta materials show the existence of Sn-O-Sn, Sn-O-Sc and Sc-O-Sc bridging oxygen environments. A further room temperature neutron powder diffraction study on deuterated BaSn0.6Sc0.4O3-delta refines the deuteron position at the 24k crystallographic site (x, y, 0) with x = 0.579(3) and y = 0.217(3) which leads to an O-D bond distance of 0.96(1) A and suggests tilting of the proton towards the next nearest oxygen. Proton conduction was found to dominate in wet argon below 700 degrees C with total conductivity values in the range 1.8 * 10-4 to 1.1 * 10 3 S cm-1 between 300 and 600 degrees C. Electron holes govern the conduction process in dry oxidizing conditions, whilst in wet oxygen they compete with protonic defects leading to a wide mixed conduction region in the 200 to 600 degrees C temperature region, and a suppression of the conductivity at higher temperature. PMID- 27358735 TI - Harnessing nonlinear rubber swelling for bulk synthesis of anisotropic hybrid nanoparticles. AB - Asymmetric hybrid nanoparticles are at the forefront of colloidal chemistry as building blocks for novel structures and applications, as well as for exploring fundamental ways of breaking symmetry in physical systems. Current methods of synthesis have significant limitations in terms of control over synthesis, particle size ranges and polydispersity. We report a facile and scalable synthesis based on the anisotropic swelling of rubber to obtain metal-(polymer rubber) hybrid nanoparticles. Initial Au nanoparticle (NP) seeds are grown larger by reducing HAuCl4 with divinyl benzene (DVB), while simultaneous radical polymerization of DVB forms a cross-linked rubber layer of PDVB on the Au NP surface. The propensity of rubber to swell nonlinearly in the presence of DVB monomers amplifies initial asymmetries to break the symmetry of the PDVB shell, causing growth of asymmetric protrusions on one side of the core-shell particles, which are fixed by further polymerization. Plasmonic absorption of Au allows us to follow the Au reduction reaction and also suggests potential applications of some of the asymmetric particles in plasmon-enhanced sensing. The polydispersity, determined statistically from TEM and SEM images, of the resulting particles is low (<10%) and their sizes, shapes and metal-polymer ratios are easily tunable. PMID- 27358736 TI - Unravelling the chemical design of spin-crossover nanoparticles based on iron(ii) triazole coordination polymers: towards a control of the spin transition. AB - A systematic study of the key synthetic parameters that control the growth of spin-crossover (SCO) nanoparticles (NPs) using the reverse micelle technique has been undertaken in the system [Fe(Htrz)2(trz)](BF4).H2O, (Htrz = 1,2,4-triazole). This has permitted us to modulate the physical properties of the NPs in a controlled and reproducible manner. In particular, a control over the size of the NPs (in the range 4 to 16 nm) has been achieved by varying the water to surfactant molar ratio. The consequences of this size variation on the cooperativity of the spin transition are discussed. Finally, this approach has been extended to the chemical alloy [Fe(Htrz)2.95(NH2trz)0.05](ClO4)2 in order to prepare NPs exhibiting a cooperative and hysteretic spin transition centred closer to room temperature. PMID- 27358737 TI - Transition-metal-nitride-based thin films as novel energy harvesting materials. AB - The last few years have seen a rise in the interest in early transition-metal and rare-earth nitrides, primarily based on ScN and CrN, for energy harvesting by thermoelectricity and piezoelectricity. This is because of a number of important advances, among those the discoveries of exceptionally high piezoelectric coupling coefficient in (Sc,Al)N alloys and of high thermoelectric power factors of ScN-based and CrN-based thin films. These materials also constitute well defined model systems for investigating thermodynamics of mixing for alloying and nanostructural design for optimization of phase stability and band structure. These features have implications for and can be used for tailoring of thermoelectric and piezoelectric properties. In this highlight article, we review the ScN- and CrN-based transition-metal nitrides for thermoelectrics, and drawing parallels with piezoelectricity. We further discuss these materials as a models systems for general strategies for tailoring of thermoelectric properties by integrated theoretical-experimental approaches. PMID- 27358738 TI - A novel design strategy for nanoparticles on nanopatterns: interferometric lithographic patterning of Mms6 biotemplated magnetic nanoparticles. AB - Nanotechnology demands the synthesis of highly precise, functional materials, tailored for specific applications. One such example is bit patterned media. These high-density magnetic data-storage materials require specific and uniform magnetic nanoparticles (MNPs) to be patterned over large areas (cm2 range) in exact nanoscale arrays. However, the realisation of such materials for nanotechnology applications depends upon reproducible fabrication methods that are both precise and environmentally-friendly, for cost-effective scale-up. A potentially ideal biological fabrication methodology is biomineralisation. This is the formation of inorganic minerals within organisms, and is known to be highly controlled down to the nanoscale whilst being carried out under ambient conditions. The magnetotactic bacterium Magnetospirillum magneticum AMB-1 uses a suite of dedicated biomineralisation proteins to control the formation of magnetite MNPs within their cell. One of these proteins, Mms6, has been shown to control formation of magnetite MNPs in vitro. We have previously used Mms6 on micro-contact printed (MUCP) patterned self-assembled monolayer (SAM) surfaces to control the formation and location of MNPs in microscale arrays, offering a bioinspired and green-route to fabrication. However, MUCP cannot produce patterns reliably with nanoscale dimensions, and most alternative nanofabrication techniques are slow and expensive. Interferometric lithography (IL) uses the interference of laser light to produce nanostructures over large areas via a simple process implemented under ambient conditions. Here we combine the bottom up biomediated approach with a top down IL methodology to produce arrays of uniform magnetite MNPs (86 +/- 21 nm) with a period of 357 nm. This shows a potentially revolutionary strategy for the production of magnetic arrays with nanoscale precision in a process with low environmental impact, which could be scaled readily to facilitate large-scale production of nanopatterned surface materials for technological applications. PMID- 27358739 TI - Actinomyces urinae sp. nov., isolated from 13-year-old girl affected by nephritic syndrome. AB - Here, we report the main characteristics of Actinomyces urinae strain Marseille P2225(T) (CSURP2225) isolated from a human urine sample. PMID- 27358740 TI - Tessaracoccus massiliensis sp. nov., a new bacterial species isolated from the human gut. AB - A new Actinobacterium, designated Tessaracoccus massiliensis type strain SIT-7(T) (= CSUR P1301 = DSM 29060), have been isolated from a Nigerian child with kwashiorkor. It is a facultative aerobic, Gram positive, rod shaped, non spore forming, and non motile bacterium. Here, we describe the genomic and phenotypic characteristics of this isolate. Its 3,212,234 bp long genome (1 chromosome, no plasmid) exhibits a G+C content of 67.81% and contains 3,058 protein-coding genes and 49 RNA genes. PMID- 27358741 TI - 'Neglecta timonensis' gen. nov., sp. nov., a new human-associated species. AB - We herein describe the main characteristics of 'Neglecta timonensis' strain SN17 (CSUR P2265) that was isolated from the stool of an 88-year-old woman with type 2 diabetes. PMID- 27358742 TI - 'Eisenbergiella massiliensis', a new species isolated from human stool collected after bariatric surgery. AB - We report the principal characteristics of 'Eisenbergiella massiliensis' sp. nov. strain AT11 (CSURP = P2120, DSM = 101499) that was isolated from a stool sample collected after bariatric surgery of a 56-year-old obese French woman. PMID- 27358743 TI - Emerging ST121/agr4 community-associated methicillin-resistant Staphylococcus aureus (MRSA) with strong adhesin and cytolytic activities: trigger for MRSA pneumonia and fatal aspiration pneumonia in an influenza-infected elderly. AB - The pathogenesis of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia in influenza-infected elderly individuals has not yet been elucidated in detail. In the present study, a 92-year-old man infected with influenza developed CA-MRSA pneumonia. His CA-MRSA was an emerging type, originated in ST121/agr4 S. aureus, with diversities of Panton-Valentine leucocidin (PVL)(-)/spat5110/SCCmecV(+) versus PVL(+)/spat159((etc.))/SCCmec (-), but with common virulence potentials of strong adhesin and cytolytic activities. Resistance to erythromycin/clindamycin (inducible-type) and gentamicin was detected. Pneumonia improved with the administration of levofloxacin, but with the subsequent development of fatal aspiration pneumonia. Hence, characteristic CA-MRSA with strong adhesin and cytolytic activities triggered influenza-related sequential complications. PMID- 27358744 TI - 'Lascolabacter vaginalis' strain KHD1, a new bacterial species cultivated from human female genital tract. AB - We present the major characteristics of 'Lascolabacter vaginalis' strain KHD1 (= CSUR P0109 = DSM 101752), a new member of the family Prevotellaceae that was cultivated from a vaginal sample of a 33-year-old woman with bacterial vaginosis. PMID- 27358745 TI - "Massiliomicrobiota timonensis," a new bacterial species isolated from the human gut. AB - We report the main characteristics of a new bacterium, "Massiliomicrobiota timonensis" strain SN16 (= CSUR P2264), which was isolated from the stool of a 87 year-old patient. PMID- 27358746 TI - Engineering approaches for regeneration of T lymphopoiesis. AB - T cells play a central role in immune-homeostasis; specifically in the induction of antigen-specific adaptive immunity against pathogens and mutated self with immunological memory. The thymus is the unique organ where T cells are generated. In this review, first the complex structures and functions of various thymic microcompartments are briefly discussed to identify critical engineering targets for regeneration of thymic functions in vitro and in vivo. Then the biomimetic regenerative engineering approaches are reviewed in three categories: 1) reconstruction of 3-D thymic architecture, 2) cellular engineering, and 3) biomaterials-based artificial presentation of critical biomolecules. For each engineering approach, remaining challenges and clinical opportunities are also identified and discussed. PMID- 27358747 TI - Prevalence of left atrial abnormalities in atrial fibrillation versus normal sinus patients. AB - BACKGROUND: Atrial fibrillation (AF) may be the cause or sequela of left atrial abnormalities and variants. PURPOSE: To determine the prevalence of left atrial (LA) abnormalities in AF patients compared to normal sinus rhythm (NSR) patients. MATERIAL AND METHODS: We retrospectively reviewed 281 cardiac CT examinations from 2010 to 2012, excluding patients with prior pulmonary vein ablation, known coronary artery disease, prior coronary stent placement, or coronary artery bypass grafts. The first group consisted of 159 AF patients undergoing cardiac CT prior to pulmonary vein ablation and the second group consisted of 122 NSR patients evaluated with coronary CT angiography. Demographic data were collected. LA abnormalities were analyzed. Left atrial diameter was measured on an axial view. RESULTS: A total of 281 patients were included. The male gender has significantly higher prevalence of AF than female gender, P value <0.001. Patients with AF were significantly older (mean age, 57.4 years; standard deviation [SD], 11.8 years) than NSR patients (mean age, 53.4 years; SD, 13.6 years), P value, 0.01. The left atrial diameter was greater in the AF patients (mean diameter, 4.3 cm; SD, 0.82 cm) versus the NSR patients (3.4 cm; SD, 0.58 cm), P value, <0.0001. LA diverticulum was the most prevalent variant, occurring in 28.4% of the entire patient population followed by LA pouch, occurring in 24%. There was no significant between group differences in the prevalence of these or the remainder of the LA variants. CONCLUSION: AF patients differed significantly from NSR patients in LA size, gender, and mean age. There was no statistical significance between the two groups with regard to the LA morphologic abnormalities other than size. PMID- 27358748 TI - Bisphenol A-associated alterations in genome-wide DNA methylation and gene expression patterns reveal sequence-dependent and non-monotonic effects in human fetal liver. AB - Bisphenol A (BPA), a high production volume chemical widely used in consumer products, is an endocrine active compound associated with complex epigenetic responses in animal models and humans. Developmental BPA exposure in mice previously revealed widespread changes in the mouse liver methylome. Here, we undertake the first epigenome-wide analysis of the effect of BPA concentration on human fetal liver DNA methylation. Enzymatic enrichment of genomic DNA for high CG density and methylation followed by next-generation sequencing yielded data for positional methylation across the genome. Comparing three groups of BPA exposed subjects (n=18; 6 per group), high (35.44-96.76 ng/g), low (3.50 to 5.79 ng/g), and non-detect (<0.83 ng/g), revealed regions of altered methylation. Similar numbers of regions of altered methylations were detected in pairwise comparisons; however, their genomic locations were distinct between the non detect and low or high BPA groups. In general, BPA levels were positively associated with methylation in CpG islands and negatively associated with methylation in CpG shores, shelves, and repetitive regions. DNA methylation at the SNORD imprinted cluster (15q11q13) illustrated both linear and non-monotonic associations with BPA levels. Integrated methylation and RNA-sequencing gene expression analysis revealed differential regulation of transcription at low BPA levels, as well as expression changes in RNA for ligand-binding proteins as BPA levels increase. BPA levels in human fetal liver tissue are associated with complex linear and non-monotonic as well as sequence-dependent alterations in DNA methylation. Future longitudinal studies are needed to link these changes with altered health risks. PMID- 27358749 TI - Genomic insights into the ESBL and MCR-1-producing ST648 Escherichiacoli with multi-drug resistance. AB - Polymyxin acts as an ultimate line of refuge against the severe infections by multidrug-resistant Gram-negative pathogens. This conventional idea is challenged dramatically by the recent discovery of mobile colistin resistance gene (mcr-1) is prevalent in food animals and human beings worldwide. More importantly, the mcr-1 gene was found to be co-localized with other antibiotic resistance genes, raising the possibility that super-bugs with pan-drug resistance are emerging. However, little is reported on the genomes of the mcr-1-positive bacterial host reservoirs. Here we report genome sequencing of three human isolates of the mcr-1 positive Escherichia coli (E15004, E15015 and E15017) and define general features through analyses of bacterial comparative genomics. Further genomic mining together with sequence typing allowed us to elucidate that the MCR-1-carrying E. coli E15017 belongs to the sequence type ST648 and coproduces extended-spectrum beta-lactamase (ESBL). Given the fact that ST648 has been known to associate with either New Delhi metallo-beta-lactamase 1 or ESBL, our results highlighted the possibility of ST648 as an epidemic clone with multidrug resistances. PMID- 27358750 TI - Circulating Fibroblast Growth Factor 21 (Fgf21) as Diagnostic and Prognostic Biomarker in Renal Cancer. AB - BACKGROUND: The finding of new biomarkers is needed to have a better sub classification of primary renal tumors (RCC) as well as more reliable predictors of outcome and therapy response. In this study, we evaluated the role of circulating FGF21, an endocrine factor, as a diagnostic and prognostic biomarker for ccRCC. MATERIALS AND METHODS: Serum samples from healthy controls (HC), clear cell and chromophobe RCC cancer patients were obtained from the serum biobank "Biobanco Publico de Muestras Sericas Oncologicas" (BPMSO) of the "Instituto de Oncologia "Angel H. Roffo". Serum FGF21 and leptin were measured by ELISA while other metabolic markers were measured following routinely clinical procedures. RESULTS: One of our major findings was that FGF21 levels were significantly increased in ccRCC patients compared with HC. Moreover, we showed an association between the increased serum FGF21 levels and the shorter disease free survival in a cohort of 98 ccRCC patients, after adjustment for other predictors of outcome. CONCLUSION: Our results suggest that higher FGF21 serum level is an independent prognostic biomarker, associated with worse free-disease survival. PMID- 27358752 TI - Of microneedles and ultrasound: Physical modes of gastrointestinal macromolecule delivery. PMID- 27358751 TI - Plant derived edible nanoparticles as a new therapeutic approach against diseases. AB - In plant cells, nanoparticles containing miRNA, bioactive lipids and proteins serve as extracellular messengers to mediate cell-cell communication in a manner similar to the exosomes secreted by mammalian cells. Notably, such nanoparticles are edible. Moreover, given the proper origin and cargo, plant derived edible nanoparticles could function in interspecies communication and may serve as natural therapeutics against a variety of diseases. In addition, nanoparticles made of plant-derived lipids may be used to efficiently deliver specific drugs. Plant derived edible nanoparticles could be more easily scaled up for mass production, compared to synthetic nanoparticles. In this review, we discuss recent significant developments pertaining to plant derived edible nanoparticles and provide insight into the use of plants as a bio-renewable, sustainable, diversified platform for the production of therapeutic nanoparticles. PMID- 27358753 TI - Tissue barriers and novel approaches to achieve hepatoselectivity of subcutaneously-injected insulin therapeutics. AB - Current subcutaneously (s.c.)-injected insulin (INS) products result in a hyperinsulin exposure to peripheral tissues (skeletal muscle and adipose) while INS hardly accesses to liver after injection. This unphysiological distribution raises risks of hypoglycemia episode and causes weight gain after long term treatment. An ideal INS replacement therapy requires the distribution or action of exogenous INS to more closely mimic physiological INS in terms of its preferential hepatic action. However, there are 2 factors that limit the ability of s.c. injected INS to restore the liver: peripheral gradient in INS deficient diabetes patients: (1) the transport of INS in capillary endothelium and peripheral tissues from the injection site; and (2) peripheral INS receptor (IR) mediated INS degradation. In this review, the tissue barriers against efficient liver targeting of s.c. injected INS are discussed and current advances in developing hepatoselective insulin therapeutics are introduced. PMID- 27358754 TI - Chemically modified peptides and proteins - critical considerations for oral delivery. AB - Numerous approaches have been explored to date in the pursuit of delivering peptides or proteins via the oral route. One such example is chemical modification, whereby the native structure of a peptide or protein is tailored to provide a more efficient uptake across the epithelial barrier of the gastrointestinal tract via incorporation of a chemical motif or moiety. In this regard, a diverse array of concepts have been reported, ranging from the exploitation of endogenous transport mechanisms to incorporation of physicochemical modifications in the molecule, which promote more favorable interactions with the absorptive membrane at the cell surface. This review provides an overview of the modification technologies described in the literature and offers insights into some pragmatic considerations pertaining to their translation into clinically viable concepts. PMID- 27358755 TI - Poly(amido amine) dendrimers in oral delivery. AB - Poly(amidoamine) (PAMAM) dendrimers have been extensively investigated for oral delivery applications due to their ability to translocate across the gastrointestinal epithelium. In this Review, we highlight recent advances in the evaluation of PAMAM dendrimers as oral drug delivery carriers. Specifically, toxicity, mechanisms of transepithelial transport, models of the intestinal epithelial barrier including isolated human intestinal tissue model, detection of dendrimers, and surface modification are discussed. We also highlight evaluation of various PAMAM dendrimer-drug conjugates for their ability to transport across gastrointestinal epithelium for improved oral bioavailability. In addition, current challenges and future trends for clinical translation of PAMAM dendrimers as carriers for oral delivery are discussed. PMID- 27358756 TI - Safety concerns over the use of intestinal permeation enhancers: A mini-review. AB - Intestinal permeation enhancers (PEs) are key components in ~12 oral peptide formulations in clinical trials for a range of molecules, primarily insulin and glucagon-like-peptide 1 (GLP-1) analogs. The main PEs comprise medium chain fatty acid-based systems (sodium caprate, sodium caprylate, and N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC)), bile salts, acyl carnitines, and EDTA. Their mechanism of action is complex with subtle differences between the different molecules. With the exception of SNAC and EDTA, most PEs fluidize the plasma membrane causing plasma membrane perturbation, as well as enzymatic and intracellular mediator changes that lead to alteration of intestinal epithelial tight junction protein expression. The question arises as to whether PEs can cause irreversible epithelial damage and tight junction openings sufficient to permit co-absorption of payloads with bystander pathogens, lipopolysaccharides and its fragment, or exo- and endotoxins that may be associated with sepsis, inflammation and autoimmune conditions. Most PEs seem to cause membrane perturbation to varying extents that is rapidly reversible, and overall evidence of pathogen co absorption is generally lacking. It is unknown however, whether the intestinal epithelial damage-repair cycle is sustained during repeat-dosing regimens for chronic therapy. PMID- 27358758 TI - Erratum. AB - [This corrects the article DOI: 10.1080/21688370.2016.1142493.]. PMID- 27358757 TI - Cell-penetrating peptides as tools to enhance non-injectable delivery of biopharmaceuticals. AB - Non-injectable delivery of peptide and protein drugs is hampered by their labile nature, hydrophilicity, and large molecular size; thus limiting their permeation across mucosae, which represent major biochemical and physical barriers to drugs administered via e.g. the oral, nasal, and pulmonary routes. However, in recent years cell-penetrating peptides (CPP) have emerged as promising tools to enhance mucosal delivery of co-administered or conjugated peptide and protein cargo and more advanced CPP-cargo formulations are emerging. CPPs act as transepithelial delivery vectors, but the mechanism(s) by which CPPs mediate cargo translocation across an epithelium is so far poorly understood; both due to the fact that multiple factors influence the resulting uptake and trafficking mechanisms as well as to the complicated nature of sensitive studies of this. In addition to a proper mechanistic understanding, documentation of CPP-mediated delivery in higher animal species than rodent as well as extensive toxicological studies are necessary for CPP-containing non-injectable DDSs to reach the clinic. PMID- 27358759 TI - Introduction for the special issue on recent advances in drug delivery across tissue barriers. AB - This special issue of Tissue Barriers contains a series of reviews with the common theme of how biological barriers established at epithelial tissues limit the uptake of macromolecular therapeutics. By improving our functional understanding of these barriers, the majority of the authors have highlighted potential strategies that might be applied to the non-invasive delivery of biopharmaceuticals that would otherwise require an injection format for administration. Half of the articles focus on the potential of particular technologies to assist oral delivery of peptides, proteins and other macromolecules. These include use of prodrug chemistry to improve molecule stability and permeability, and the related potential for oral delivery of poorly permeable agents by cell-penetrating peptides and dendrimers. Safety aspects of intestinal permeation enhancers are discussed, along with the more recent foray into drug-device combinations as represented by intestinal microneedles and externally-applied ultrasound. Other articles highlight the crossover between food research and oral delivery based on nanoparticle technology, while the final one provides a fascinating interpretation of the physiological problems associated with subcutaneous insulin delivery and how inefficient it is at targeting the liver. PMID- 27358760 TI - Cybercare 2.0: meeting the challenge of the global burden of disease in 2030. AB - In this paper, we propose to advance and transform today's healthcare system using a model of networked health care called Cybercare. Cybercare means "health care in cyberspace" - for example, doctors consulting with patients via videoconferencing across a distributed network; or patients receiving care locally - in neighborhoods, "minute clinics," and homes - using information technologies such as telemedicine, smartphones, and wearable sensors to link to tertiary medical specialists. This model contrasts with traditional health care, in which patients travel (often a great distance) to receive care from providers in a central hospital. The Cybercare model shifts health care provision from hospital to home; from specialist to generalist; and from treatment to prevention. Cybercare employs advanced technology to deliver services efficiently across the distributed network - for example, using telemedicine, wearable sensors and cell phones to link patients to specialists and upload their medical data in near-real time; using information technology (IT) to rapidly detect, track, and contain the spread of a global pandemic; or using cell phones to manage medical care in a disaster situation. Cybercare uses seven "pillars" of technology to provide medical care: genomics; telemedicine; robotics; simulation, including virtual and augmented reality; artificial intelligence (AI), including intelligent agents; the electronic medical record (EMR); and smartphones. All these technologies are evolving and blending. The technologies are integrated functionally because they underlie the Cybercare network, and/or form part of the care for patients using that distributed network. Moving health care provision to a networked, distributed model will save money, improve outcomes, facilitate access, improve security, increase patient and provider satisfaction, and may mitigate the international global burden of disease. In this paper we discuss how Cybercare is being implemented now, and envision its growth by 2030. PMID- 27358763 TI - Design of a high-mobility multi-terrain robot based on eccentric paddle mechanism. AB - Gaining high mobility on versatile terrains is a crucial target for designing a mobile robot toward tasks such as search and rescue, scientific exploration, and environment monitoring. Inspired by dextrous limb motion of animals, a novel form of locomotion has been established in our previous study, by proposing an eccentric paddle mechanism (ePaddle) for integrating paddling motion into a traditional wheeled mechanism. In this paper, prototypes of an ePaddle mechanism and an ePaddle-based quadruped robot are presented. Several locomotion modes, including wheeled rolling, legged crawling, legged race-walking, rotational paddling, oscillating paddling, and paddle-aided rolling, are experimentally verified on testbeds with fabricated prototypes. Experimental results confirm that paddle's motion is useful in all the locomotion modes. PMID- 27358764 TI - Fatal hemorrhagic pneumonia: Don't forget Stenotrophomonas maltophilia. AB - We present a case of fatal hemorrhagic pneumonia secondary to Stenotrophomonas maltophilia in a patient with acute myeloid leukemia. S. maltophilia is commonly a non-virulent pathogen. However, in the immunocompromised, it is generally associated with bacteremia after central venous catheter placement or pneumonia. Hemorrhagic pneumonia is a rare presentation of this bacteria, with only 31 cases reported in the literature, and has 100% mortality within 72 hours. Rapid recognition and early suspicion should be key in the treatment of these patients. PMID- 27358765 TI - Impaired dynamic cerebrovascular response to hypercapnia predicts development of white matter hyperintensities. AB - PURPOSE: To evaluate the relationship between both dynamic and steady-state measures of cerebrovascular reactivity (CVR) and the progression of age-related white matter disease. METHODS: Blood oxygen level-dependent (BOLD) MRI CVR scans were acquired from forty-five subjects (age range: 50-90 years, 25 males) with moderate to severe white matter disease, at baseline and one-year follow-up. To calculate the dynamic (tau) and steady-state (ssCVR) components of the BOLD signal response, the PETCO2 signal waveform was convolved with an exponential decay function. The tau corresponding to the best fit between the convolved PETCO2 and BOLD signal defined the speed of response, and the slope of the regression between the convolved PETCO2 and BOLD signal defined ssCVR. ssCVR and tau were compared between normal-appearing white matter (NAWM) that remains stable over time and NAWM that progresses to white matter hyperintensities (WMHs). RESULTS: In comparison to contralateral NAWM, NAWM that progressed to WMH had significantly lower ssCVR values by mean (SD) 46.5 (7.6)%, and higher tau values by 31.9 (9.6)% (both P < 0.01). CONCLUSIONS: Vascular impairment in regions of NAWM that progresses to WMH consists not only of decreased magnitude of ssCVR, but also a pathological decrease in the speed of vascular response. These findings support the association between cerebrovascular dysregulation and the development of WMH. PMID- 27358766 TI - Connectome-scale group-wise consistent resting-state network analysis in autism spectrum disorder. PMID- 27358767 TI - Population-based MRI atlases of spatial distribution are specific to patient and tumor characteristics in glioblastoma. AB - BACKGROUND AND PURPOSE: In treating glioblastoma (GB), surgical and chemotherapeutic treatment guidelines are, for the most part, independent of tumor location. In this work, we compiled imaging data from a large cohort of GB patients to create statistical atlases illustrating the disease spatial frequency as a function of patient demographics as well as tumor characteristics. MATERIALS AND METHODS: Two-hundred-six patients with pathology-proven glioblastoma were included. Of those, 65 had pathology-proven recurrence and 113 had molecular subtype and genetic information. We used validated software to segment the tumors in all patients and map them from patient space into a common template. We then created statistical maps that described the spatial location of tumors with respect to demographics and tumor characteristics. We applied a chi-square test to determine whether pattern differences were statistically significant. RESULTS: The most frequent location for glioblastoma in our patient population is the right temporal lobe. There are statistically significant differences when comparing patterns using demographic data such as gender (p = 0.0006) and age (p = 0.006). Small and large tumors tend to occur in separate locations (p = 0.0007). The tumors tend to occur in different locations according to their molecular subtypes (p < 10(- 6)). The classical subtype tends to spare the frontal lobes, the neural subtype tend to involve the inferior right frontal lobe. Although the sample size is limited, there was a difference in location according to EGFR VIII genotype (p < 10(- 4)), with a right temporal dominance for EFGR VIII negative tumors, and frontal lobe dominance in EGFR VIII positive tumors. CONCLUSIONS: Spatial location of GB is an important factor that correlates with demographic factors and tumor characteristics, which should therefore be considered when evaluating a patient with GB and might assist in personalized treatment. PMID- 27358768 TI - Parasite species of the endangered Iberian wolf (Canis lupus signatus) and a sympatric widespread carnivore. AB - Parasites have a profound impact on wildlife population dynamics. However, until some years ago, studies on the occurrence and prevalence of wildlife parasites were neglected comparatively with the studies on humans and domestic animals. In this study, we determined the parasite prevalence of two sympatric wild canids: the endangered Iberian wolf (Canis lupus signatus) and the widespread red fox (Vulpes vulpes), in central Portugal. From November 2014 to July 2015, fresh fecal samples from both species were collected monthly in several transects distributed throughout the study area. All samples were submitted to several coprological techniques. In total, 6 helminth parasites (Crenosoma vulpis, Angiostrongylus vasorum, Toxocara canis, Trichuris vulpis, Ancylostomatidae, Toxascaris leonina), and a protozoa (Balantidium coli) were identified based on size and morphology. The red fox was infected by seven different parasites while the Iberian wolf was infected by four. All parasites present in wolf were also present in the red fox. C. vulpis had the higher prevalence in red fox, while Ancylostomatidae were the most prevalent parasites in wolf. To our knowledge, this is the first study in this isolated subpopulation of the Iberian wolf. Our results show that both carnivores carry parasites that are of concern as they are pathogenic to humans and other wild and domestic animals. We suggest that surveillance programs must also include monitoring protocols of wildlife; particularly endangered species. PMID- 27358769 TI - Occipital seizures and persistent homonymous hemianopia with T2 hypointensity on MRI in nonketotic hyperglycemia. AB - INTRODUCTION: Nonketotic hyperglycemia (NKH) is known to cause focal motor or secondarily generalized seizures. Occipital seizures in NKH are seldom reported, especially with visual hallucinations and persistent homonymous hemianopia (HH) with characteristic radiological and electroencephalographic (EEG) findings. SUMMARY: Our patient was a middle-aged man who presented with a new onset, single episode of generalized tonic-clonic seizure and NKH. He complained of seeing intermittent colorful stripes in his right visual field. Examination revealed persistent complete right HH and he was observed to have complex partial seizures. Magnetic resonance imaging (MRI) showed subcortical T2 hypointensity within the left occipital lobe in T2W and FLAIR images. The EEG showed electrographic seizures originating from the left occipital region. Random blood glucose at presentation was 581 mg/dl with HbA1c of 11.4%. The seizure and visual field deficits were successfully terminated by the introduction of antiseizure medication and glycemic control. CONCLUSION: Occipital seizures with visual field deficits can occur in hyperglycemic states. These can be associated with specific MRI brain and EEG changes. The HH is reversible with apt treatment primarily including glycemic control with or without antiseizure medication. PMID- 27358770 TI - Marked improvement in febrile infection-related epilepsy syndrome after lidocaine plus MgSO4 treatment in a 12-year-old girl. AB - PURPOSE: This report sheds light on a successful treatment in febrile infection related epilepsy syndrome (FIRES) with the combined use of lidocaine and MgSO4. METHODS: We report a 12-year-old previously healthy girl who experienced an upper respiratory infection with fever and headache for 2 days, then suddenly went into a coma followed by repetitive status epilepticus. All tests for CNS infection, metabolic and toxic diseases, and autoimmune encephalitis were negative. Hence, the diagnosis of FIRES was made. During 5 weeks of hospital treatment, various antiepileptic drugs were administered at different times without success. To achieve seizure control, we then attempted the use of lidocaine first, then followed by MgSO4. RESULTS: The SE was successfully controlled when lidocaine plus MgSO4 was introduced. At follow-up, almost no neurological sequelae remained. CONCLUSION: This is the first report describing the combined use of lidocaine and MgSO4 with successful treatment outcomes. This experience has indicated that even FIRES can be controlled if treated promptly with certain agents. However, more studies are needed to explore the mechanisms and effects of lidocaine and MgSO4 in FIRES. PMID- 27358772 TI - Hepatoduodenal ligament dissection technique during recipient hepatectomy for liver transplantation: How I do it? AB - Accurate dissection of the hepatoduodenal ligament in the recipient is vital for the success of liver transplantation surgery. High incidence of anatomic variations at the hepatic artery, portal vein and biliary ducts in the hepatoduodenal ligament is well known. Surgical experience is important to be able to foresee the most common anatomic diversities and the possible variations, in order to make a safe and accurate dissection in the hepatic hilum. Before anastomosis, all these hilar structures must be well identified, safely dissected and must also have a sufficient length for the coming implantation process. At the beginning of our program, we were starting the hepatic hilum dissection close to the liver. In time, however, we modified our surgical technique, preferring to start further away from the liver (closer to the duodenum). This length increased progressively over 1500 liver transplantations (80% living donor liver transplantation). During this process, our main purpose was the early control of the hepatic artery (artery first approach). In this paper, our aim is to share our latest version of the hepatoduodenal ligament dissection technique. We also describe alternative approaches used in extraordinary situations. PMID- 27358771 TI - Exocrine drainage in vascularized pancreas transplantation in the new millennium. AB - The history of vascularized pancreas transplantation largely parallels developments in immunosuppression and technical refinements in transplant surgery. From the late-1980s to 1995, most pancreas transplants were whole organ pancreatic grafts with insulin delivery to the iliac vein and diversion of the pancreatic ductal secretions to the urinary bladder (systemic-bladder technique). The advent of bladder drainage revolutionized the safety and improved the success of pancreas transplantation. However, starting in 1995, a seismic change occurred from bladder to bowel exocrine drainage coincident with improvements in immunosuppression, preservation techniques, diagnostic monitoring, general medical care, and the success and frequency of enteric conversion. In the new millennium, pancreas transplants are performed predominantly as pancreatico duodenal grafts with enteric diversion of the pancreatic ductal secretions coupled with iliac vein provision of insulin (systemic-enteric technique) although the systemic-bladder technique endures as a preferred alternative in selected cases. In the early 1990s, a novel technique of venous drainage into the superior mesenteric vein combined with bowel exocrine diversion (portal-enteric technique) was designed and subsequently refined over the next >= 20 years to re create the natural physiology of the pancreas with first-pass hepatic processing of insulin. Enteric drainage usually refers to jejunal or ileal diversion of the exocrine secretions either with a primary enteric anastomosis or with an additional Roux limb. The portal-enteric technique has spawned a number of newer and revisited techniques of enteric exocrine drainage including duodenal or gastric diversion. Reports in the literature suggest no differences in pancreas transplant outcomes irrespective of type of either venous or exocrine diversion. The purpose of this review is to examine the literature on exocrine drainage in the new millennium (the purported "enteric drainage" era) with special attention to technical variations and nuances in vascularized pancreas transplantation that have been proposed and studied in this time period. PMID- 27358773 TI - Liver transplantation and the management of progressive familial intrahepatic cholestasis in children. AB - Progressive familial intrahepatic cholestasis (PFIC) is a constellation of inherited disorders that result in the impairment of bile flow through the liver that predominantly affects children. The accumulation of bile results in progressive liver damage, and if left untreated leads to end stage liver disease and death. Patients often present with worsening jaundice and pruritis within the first few years of life. Many of these patients will progress to end stage liver disease and require liver transplantation. The role and timing of liver transplantation still remains debated especially in the management of PFIC1. In those patients who are appropriately selected, liver transplantation offers an excellent survival benefit. Appropriate timing and selection of patients for liver transplantation will be discussed, and the short and long term management of patients post liver transplantation will also be described. PMID- 27358775 TI - Loco-regional therapies for patients with hepatocellular carcinoma awaiting liver transplantation: Selecting an optimal therapy. AB - Hepatocellular carcinoma (HCC) is a common, increasingly prevalent malignancy. For all but the smallest lesions, surgical removal of cancer via resection or liver transplantation (LT) is considered the most feasible pathway to cure. Resection - even with favorable survival - is associated with a fairly high rate of recurrence, perhaps since most HCCs occur in the setting of cirrhosis. LT offers the advantage of removing not only the cancer but the diseased liver from which the cancer has arisen, and LT outperforms resection for survival with selected patients. Since time waiting for LT is time during which HCC can progress, loco-regional therapy (LRT) is widely employed by transplant centers. The purpose of LRT is either to bridge patients to LT by preventing progression and waitlist dropout, or to downstage patients who slightly exceed standard eligibility criteria initially but can fall within it after treatment. Transarterial chemoembolization and radiofrequency ablation have been the most widely utilized LRTs to date, with favorable efficacy and safety as a bridge to LT (and for the former, as a downstaging modality). The list of potentially effective LRTs has expanded in recent years, and includes transarterial chemoembolization with drug-eluting beads, radioembolization and novel forms of extracorporal therapy. Herein we appraise the various LRT modalities for HCC, and their potential roles in specific clinical scenarios in patients awaiting LT. PMID- 27358774 TI - Massive haemorrhage in liver transplantation: Consequences, prediction and management. AB - From its inception the success of liver transplantation has been associated with massive blood loss. Massive transfusion is classically defined as > 10 units of red blood cells within 24 h, but describing transfusion rates over a shorter period of time may reduce the potential for survival bias. Both massive haemorrhage and transfusion are associated with increased risk of mortality and morbidity (need for dialysis/surgical site infection) following liver transplantation although causality is difficult to prove due to the observational design of most trials. The blood loss associated with liver transplantation is multifactorial. Portal hypertension secondary to cirrhosis results in extensive collateral circulation, which can bleed during hepatectomy particular if portal pressures are increased. Avoiding volume loading and maintenance of a low central venous pressure together with the use of vasopressors have been shown to reduce blood loss and transfusion during liver transplantation, but may increase the risk of renal impairment post-operatively. Coagulation defects may be present pre transplant, but haemostasis is often re-balanced due to a deficit in both pro- and anti-coagulation factors. Further derangement of haemostasis may develop in the anhepatic and neohepatic phases due to absent hepatic metabolic function, hyperfibrinolysis and platelet sequestration in the donor liver. Point-of-care tests of coagulation such as the viscoelastic tests rotation thromboelastometry/thromboelastometry allow and more accurate and rapid assessment of these derangements in coagulation and guide the use of factor replacement and antifibrinolytics. Transfusion protocols guided by these tests have been shown to reduce transfusion rates compared with conventional coagulation tests, but have not shown improvements in mortality or morbidity. Pre operative factors associated with massive transfusion include previous surgery, re-do transplantation, the aetiology and severity of liver disease. Intra operatively the use of piggy-back technique and avoiding veno-veno bypass has been shown to reduced blood loss. PMID- 27358776 TI - Potential approaches to improve the outcomes of donation after cardiac death liver grafts. AB - There is a growing discrepancy between the supply and demand of livers for transplantation resulting in high mortality rates on the waiting list. One of the options to decrease the mortality on the waiting list is to optimize organs with inferior quality that otherwise would be discarded. Livers from donation after cardiac death (DCD) donors are frequently discarded because they are exposed to additional warm ischemia time, and this might lead to primary-non-function, delayed graft function, or severe biliary complications. In order to maximize the usage of DCD livers several new preservation approaches have been proposed. Here, we will review 3 innovative organ preservation methods: (1) different ex vivo perfusion techniques; (2) persufflation with oxygen; and (3) addition of thrombolytic therapy. Improvement of the quality of DCD liver grafts could increase the pool of liver graft's for transplantation, improve the outcomes, and decrease the mortality on the waiting list. PMID- 27358777 TI - First line vs delayed transplantation in myeloma: Certainties and controversies. AB - Since the middle of 1990s autologous stem cell transplantation has been the cornerstone for the treatment of young patients with multiple myeloma (MM). In the last decade the introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (PI), has dramatically changed the therapeutic scenario of this yet incurable disease. Due to the impressive results achieved with IMiDs and PI both in terms of response rates and in terms of progression free and overall survival, and to the toxicity linked to high dose therapy and autologous stem cell transplantation (ASCT), a burning question nowadays is whether all young patients should be offered autotransplantation up front or if this should be reserved for the time of relapse. This article provides a review of the data available regarding ASCT in MM and of the current opinion of the scientific community regarding its optimal timing. PMID- 27358778 TI - State of deceased donor transplantation in India: A model for developing countries around the world. AB - Renal replacement therapy (RRT) resources are scarce in India, with wide urban rural and interstate disparities. The burden of end-stage renal disease is expected to increase further due to increasing prevalence of risk factors like diabetes mellitus. Renal transplantation, the best RRT modality, is increasing in popularity, due to improvements made in public education, the deceased donor transplantation (DDT) programme and the availability of free and affordable transplant services in government hospitals and certain non-governmental philanthropic organizations. There are about 120000 haemodialysis patients and 10000 chronic peritoneal dialysis patients in India, the majority of them waiting for a donor kidney. Shortage of organs, lack of transplant facilities and high cost of transplant in private facilities are major barriers for renal transplantation in India. The DDT rate in India is now 0.34 per million population, among the lowest in the world. Infrastructural development in its infancy and road traffic rules not being strictly implemented by the authorities, have led to road traffic accidents being very common in urban and rural India. Many patients are declared brain dead on arrival and can serve as potential organ donors. The DDT programme in the state of Tamil Nadu has met with considerable success and has brought down the incidence of organ trade. Government hospitals in Tamil Nadu, with a population of 72 million, provide free transplantation facilities for the underprivileged. Public private partnership has played an important role in improving organ procurement rates, with the help of trained transplant coordinators in government hospitals. The DDT programmes in the southern states of India (Tamil Nadu, Kerala, Pondicherry) are advancing rapidly with mutual sharing due to public private partnership providing vital organs to needy patients. Various health insurance programmes rolled out by the governments in the southern states are effective in alleviating financial burden for the transplantation. Post-transplant immunological and pathological surveillance of recipients remains a challenge due to the scarcity of infrastructure and other facilities. PMID- 27358779 TI - Role of cytomegalovirus on the maturation and function of monocyte derived dendritic cells of liver transplant patients. AB - AIM: To study the impact of association between cytomegalovirus (CMV) pathogenesis with dendritic cell (DC) maturation and function was evaluated in CMV reactivated liver transplanted patients in comparing with non-reactivated ones, and healthy controls. METHODS: Monocyte derived dendritic cells (MoDCs) was generated from collected ethylenediaminetetraacetic acid-treated blood samples from patient groups and controls. In these groups, expression rates and mean fluorescent intensity of DC markers were evaluated using flowcytometry technique. Secretion of cytokines including: interleukin (IL)-6, IL-12 and IL-23 were determined using enzyme-linked immunosorbent assay methods. The gene expression of toll-like receptor 2 (TLR2), TLR4 and IL-23 were analyzed using in-house real time polymerase chain reaction protocols. RESULTS: Results have been shown significant decreases in: Expression rates of MoDC markers including CD83, CD1a and human leukocyte antigen DR (HLA-DR), the mean fluorescence intensitys for CD1a and HLA-DR, and secretion of IL-12 in CMV reactivated compared with non reactivated liver transplanted patients. On the other hand, significant increases have been shown in the secretions of IL-6 and IL-23 and gene expression levels of TLR2, TLR4 and IL-23 from MoDCs in CMV reactivated compared with non-reactivated liver transplanted recipients. CONCLUSION: DC functional defects in CMV reactivated recipients, such as decrease in expression of DC maturation markers, increase in secretion of proinflammatory cytokines, and TLRs can emphasize on the importance of CMV infectivity in development of liver rejection in transplanted patients. PMID- 27358780 TI - Single-lung transplantation in emphysema: Retrospective study analyzing survival and waiting list mortality. AB - AIM: To performed remains a subject of debate and is the principal aim of the study. METHODS: This retrospective analysis included 73 patients with emphysema (2000-2012). The outcomes of patients undergoing single-lung transplantation (SL) (n = 40) or double-lung transplant (DL) (n = 33) were compared in a Cox multivariate analysis to study the impact of the technique, postoperative complications and acute and chronic rejection on survival rates. Patients were selected for inclusion in the waiting list according to the International Society of Heart Lung Transplantation criteria. Pre and postoperative rehabilitation and prophylaxis, surgical technique and immunosuppressive treatment were similar in every patients. Lung transplantation waiting list information on a national level and retrospective data on emphysema patient survival transplanted in Spain during the study period, was obtained from the lung transplantation registry managed by the National Transplant Organization (ONT). RESULTS: Both groups were comparable in terms of gender and clinical characteristics. We found significant differences in the mean age between the groups, the DL patients being younger as expected from the inclusion criteria. Perioperative complications occurred in 27.6% SL vs 54% DL (P = 0.032). Excluding perioperative mortality, median survival was 65.3 mo for SL and 59.4 mo for DL (P = 0.96). Bronchiolitis obliterans and overall 5 year survival were similar in both groups. Bacterial respiratory infection, cytomegalovirus and fungal infection rates were higher but not significant in SL. No differences were found between type of transplant and survival (P = 0.48). To support our results, national data on all patients with emphysema in waiting list were obtained (n = 1001). Mortality on the waiting list was 2.4% for SL vs 6.2% for DL. There was no difference in 5 year survival between 235 SL and 430 DL patients transplanted (P = 0.875). CONCLUSION: Our results suggest that SL transplantation in emphysema produce similar survival than DL with less postoperative complication and significant lower mortality in waiting list. PMID- 27358781 TI - Impact of body mass index on outcomes of 48281 patients undergoing first time cadaveric liver transplantation. AB - AIM: To investigate possible disparities in perioperative morbidity and mortality among different body mass index (BMI) groups and to simulate the impact that these differences might have had on the cohort of patients undergoing cadaveric liver transplantation (LT). METHODS: All adult recipients undergoing first time LT for benign conditions and receiving a whole graft from brain-dead donors were selected from the united network of organ sharing registry. From January 1994 to June 2013, 48281 patients satisfied the inclusion criteria and were stratified by their BMI. The hypothesis that abnormal BMIs were independent predictors of inferior outcomes was tested with univariate and multivariate regression analyses. RESULTS: In comparison to normal weight recipients, underweight and morbidly obese recipients had increased 90-d mortality (adjusted OR = 1.737; 95%CI: 1.185-2.548, P = 0.005) (adjusted OR = 1.956; 95%CI: 1.473-2.597, P = 0.000) respectively and inferior patients' survivals (adjusted HR = 1.265; 95%CI: 1.096-1.461, P = 0.000) (adjusted HR = 1.157; 95%CI: 1.031-1.299, P = 0.013) respectively. Overall, patients' 5-year survival were 73.9% for normal-weight, 71.1% for underweight, 74.0% for overweight, 74.4% for class I obese, 75.0% for class II obese and 71.5% for class III obese recipients. Analysis of hypothetical exclusion of underweight and morbidly obese patients from the pool of potential LT candidates would have improved the overall survival of the entire cohort by 2.7% (95%CI: 2.5%-3.6%). CONCLUSION: Selected morbidly obese patients undergoing LT for benign conditions had 5-year survival rates clinically comparable to normal weight recipients. Impact analysis showed that exclusion of high-risk recipients (underweight and morbid obese patients) would not significantly improve the overall survival of the entire cohort of patients requiring LT. PMID- 27358782 TI - Risk factors for fracture in adult kidney transplant recipients. AB - AIM: To determine the general and transplant-specific risk factors for fractures in kidney transplant recipients. METHODS: We conducted a cohort study of all adults who received a kidney-only transplant (n = 2723) in Ontario, Canada between 2002 and 2009. We used multivariable Cox proportional hazards regression to determine general and transplant-specific risk factors for major fractures (proximal humerus, forearm, hip, and clinical vertebral). The final model was established using the backward elimination strategy, selecting risk factors with a P-value <= 0.2 and forcing recipient age and sex into the model. We also assessed risk factors for other fracture locations (excluding major fractures, and fractures involving the skull, hands or feet). RESULTS: There were 132 major fractures in the follow-up (8.1 fractures per 1000 person-years). General risk factors associated with a greater risk of major fracture were older recipient age [adjusted hazard ratio (aHR) per 5-year increase 1.11, 95%CI: 1.03-1.19] and female sex (aHR = 1.81, 95%CI: 1.28-2.57). Transplant-specific risk factors associated with a greater risk of fracture included older donor age (5-year increase) (aHR = 1.09, 95%CI: 1.02-1.17) and end-stage renal disease (ESRD) caused by diabetes (aHR = 1.72, 95%CI: 1.09-2.72) or cystic kidney disease (aHR = 1.73, 95%CI: 1.08-2.78) (compared to glomerulonephritis as the reference cause). Risk factors across the two fracture locations were not consistent (major fracture locations vs other). Specifically, general risk factors associated with an increased risk of other fractures were diabetes and a fall with hospitalization prior to transplantation, while length of time on dialysis, and renal vascular disease and other causes of ESRD were the transplant-specific risk factors associated with a greater risk of other fractures. CONCLUSION: Both general and transplant-specific risk factors were associated with a higher risk of fractures in kidney transplant recipients. Results can be used for clinical prognostication. PMID- 27358783 TI - Long term outcomes of cardiac transplant for immunoglobulin light chain amyloidosis: The Mayo Clinic experience. AB - AIM: To determine the outcome of orthotopic heart transplantation (OHT) in immunoglobulin light chain (AL) amyloidosis. METHODS: The medical records of patients with AL who underwent orthotopic heart transplantation at the Mayo Clinic in Rochester Minnesota from 1992 to 2011 were reviewed. Patients met at least one of the following at: New York Heart Association class IV heart failure, ventricular thickness > 15 mm, ejection fraction < 40%. Selection guidelines for heart transplant included age < 60 years, absence of multiple myeloma and significant extra-cardiac organ involvement. Baseline characteristics including age, gender, organ involvement, and New York Heart Association functional class were recorded. Laboratory data, waiting time until heart transplant, and type of treatment of the underlying plasma cell disorder were recorded. Survival from the time of OHT was calculated using Kaplan-Meier survival curves. Survival of patients undergoing OHT for AL was compared to that of non-amyloid patients undergoing OHT during the same time period. RESULTS: Twenty-three patients (median age 53 years) with AL received OHT. There were no deaths in the immediate perioperative period. Twenty patients have died post OHT. For the entire cohort, the median overall survival was 3.5 years (95%CI: 1.2, 8.2 years). The 1-year survival post OHT was 77%, the 2-year survival 65%, and the 5-year survival 43%. The 5-year survival for non-amyloid patients undergoing OHT during the same era was 85%. Progressive amyloidosis contributed to death in twelve patients. Of those without evidence of progressive amyloidosis, the cause of death included complications of autologous hematopoietic stem cell transplantation for 3 patients, post-transplant lymphoproliferative disorder for 2 patients; and for the remaining one death was related to each of the following causes: acute rejection; cardiac vasculopathy; metastatic melanoma; myelodysplastic syndrome; and unknown. Eight patients had rejection at a median of 1.8 mo post OHT (range 0.4 to 4.9 mo); only one patient died of rejection. Median survival of seven patients who achieved a complete hematologic response to either chemotherapy or autologous hematopoietic stem cell transplantation was 10.8 years. CONCLUSION: Our data demonstrate that long term survival after heart transplant is feasible in AL patients with limited extra-cardiac involvement who achieve complete hematologic response. PMID- 27358784 TI - Ventilator associated pneumonia following liver transplantation: Etiology, risk factors and outcome. AB - AIM: To determine the incidence, etiology, risk factors and outcome of ventilator associated pneumonia (VAP) in patients undergoing orthotopic liver transplantation (OLT). METHODS: This retrospective study considered 242 patients undergoing deceased donor OLT. VAP was diagnosed according to clinical and microbiological criteria. RESULTS: VAP occurred in 18 (7.4%) patients, with an incidence of 10 per 1000 d of mechanical ventilation (MV). Isolated bacterial etiologic agents were mainly Enterobacteriaceae (79%). Univariate logistic analysis showed that model for end-stage liver disease (MELD) score, pre operative hospitalization, treatment with terlipressin, Child-Turcotte-Pugh score, days of MV and red cell transfusion were risk factors for VAP. Multivariate analysis, considering significant risk factors in univariate analysis, demonstrated that pneumonia was strongly associated with terlipressin usage, pre-operative hospitalization, days of MV and red cell transfusion. Mortality rate was 22% in the VAP group vs 4% in the group without VAP. CONCLUSION: Our data suggest that VAP is an important cause of nosocomial infection during postoperative period in OLT patients. MELD score was a significant risk factor in univariate analysis. Multiple transfusions, treatment with terlipressin, preoperative hospitalization rather than called to the hospital while at home and days of MV constitute important risk factors for VAP development. PMID- 27358785 TI - Liver transplantation for hepatocellular carcinoma in Ireland: Pre-operative alpha-fetoprotein predicts tumour recurrence in a 14-year single-centre national experience. AB - AIM: To examine the results of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) in Ireland over a 14-year period. METHODS: Cases of HCC receiving OLT between January 1995 and September 2009 in the Irish Liver Transplant Unit were reviewed from a prospectively maintained database. Outcome measures included overall and recurrence free survival, alpha-fetoprotein (AFP) and tumour pathological features. RESULTS: On explant pathology, 57 patients had HCC. The median follow-up time was 42.7 mo. The overall 1, 3 and 5 years survival was 87.7%, 72.1% and 72.4%. There was no difference in survival when compared to patients undergoing OLT without malignancy. The tumour recurrence rate was 14%. The Milan criteria were exceeded in 32% of cases but this did not predict overall survival or recurrence. On multivariate analysis pre-operative AFP > 100 ng/mL was an independent risk factor for recurrence (RR = 5.2, CI: 1.1-24.3, P = 0.036). CONCLUSION: Patients undergoing OLT for HCC had excellent survival even when conventional listing criteria were exceeded. Pre-operative AFP predicts recurrence independent of tumour size and its role in selection criteria should be investigated in larger studies. PMID- 27358786 TI - Higher plasma bilirubin predicts veno-occlusive disease in early childhood undergoing hematopoietic stem cell transplantation with cyclosporine. AB - AIM: To analyze the association between plasma bilirubin levels and veno occlusive disease (VOD) in non-adult patients undergoing hematopoietic stem cell transplantation (HSCT) during cyclosporine therapy. METHODS: A total of 123 patients taking cyclosporine were evaluated using an electronic medical system at the Seoul National University Children's Hospital from the years 2004 through 2011. Patients were grouped by age and analyzed for incidence and type of adverse drug reactions (ADRs) including VOD. RESULTS: The HSCT patients were divided into three age groups: G#1 >= 18; 9 <= G#2 <= 17; and G#3 <= 8 years of age). The majority of transplant donor types were cord blood transplantations. Most prevalent ADRs represented acute graft-vs-host disease (aGVHD) and VOD. Although the incidences of aGVHD did not vary among the groups, the higher frequency ratios of VOD in G#3 suggested that an age of 8 or younger is a risk factor for developing VOD in HSCT patients. After cyclosporine therapy, the trough plasma concentrations of cyclosporine were lower in G#3 than in G#1, indicative of its increased clearance. Moreover, in G#3 only, a maximal total bilirubin level (BILmax) of >= 1.4 mg/dL correlated with VOD incidence after cyclosporine therapy. CONCLUSION: HSCT patients 8 years of age or younger are more at risk for developing VOD, diagnosed as hyperbilirubinemia, tender hepatomegaly, and ascites/weight gain after cyclosporine therapy, which may be represented by a criterion of plasma BILmax being >= 1.4 mg/dL, suggestive of more sensitive VOD indication in this age group. PMID- 27358787 TI - Proposal of new expanded selection criteria using total tumor size and (18)F fluorodeoxyglucose - positron emission tomography/computed tomography for living donor liver transplantation in patients with hepatocellular carcinoma: The National Cancer Center Korea criteria. AB - AIM: To expand the living donor liver transplantation (LT) pool of eligible patients with hepatocellular carcinoma (HCC) using new morphological and biological criteria. METHODS: Patients with HCC who underwent living donor LT (LDLT) from March 2005 to May 2013 at the National Cancer Center Korea (NCCK) were enrolled. We performed the (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) before LDLT. Overall and disease-free survival analysis was done in patients to evaluate the usefulness of new NCCK criteria using PET/CT and total tumor size (10 cm). RESULTS: We enrolled a total of 280 patients who pathologically confirmed to have HCC and performed the PET/CT before transplantation. Among them, 164 (58.6%) patients fulfilled the NCCK criteria and 132 patients (47.1%) met the Milan criteria. Five-year overall and disease-free survival rates for patients who fulfilled the NCCK criteria showed 85.2% and 84.0%, respectively, and were significantly higher than those beyond the NCCK criteria (60.2% and 44.4%, respectively; P < 0.001). The correlation analysis between preoperative imaging tests and pathologic reports using Cohen's Kappa demonstrated the better results in the NCCK criteria than those in the Milan criteria (0.850 vs 0.583). The comparison of disease-free analysis among the NCCK, Milan, and University of California, San Francisco (UCSF) criteria using the receiver operating characteristics curves revealed the similar area under the curve value criteria (NCCK vs Milan, P = 0.484; NCCK vs UCSF, P = 0.189 at 5-years). CONCLUSION: The NCCK criteria using hybrid concept of both morphological and biological parameters showed an excellent agreement between preoperative imaging and pathological results, and favorable survival outcomes. These new criteria might select the optimal patients with HCC waiting LDLT and expand the selection pool. PMID- 27358788 TI - Deceased donor organ procurement injuries in the United States. AB - AIM: To determine the incidence of surgical injury during deceased donor organ procurements. METHODS: Organ damage was classified into three tiers, from 1-3, with the latter rendering the organ non-transplantable. For 12 consecutive months starting in January of 2014, 36 of 58 organ procurement organization's (OPO)'s prospectively submitted quality data regarding organ damage (as reported by the transplanting surgeon and confirmed by the OPO medical director) seen on the procured organ. RESULTS: These 36 OPOs recovered 5401 of the nations's 8504 deceased donors for calendar year 2014. A total of 19043 organs procured were prospectively analyzed. Of this total, 59 organs sustained damage making them non transplantable (0 intestines; 4 pancreata; 5 lungs; 6 livers; 43 kidneys). The class 3 damage was spread over 22 (of 36) reporting OPO's. CONCLUSION: While damage to the procured organ is rare with organ loss being approximately 0.3% of procured organs, loss of potential transplantable organs does occur during procurement. PMID- 27358789 TI - Exercise manual for liver disease patients. AB - AIM: To increase inspiratory muscle strength and improve the quality of life of candidates for liver transplantation. METHODS: Twenty-three candidates for liver transplantation participated in the control group and 14 made up the intervention group. The control group consisted of 18 men and 5 women, body mass index (BMI) 27.3 +/- 4.5 kg/m(2) and Model for End-Stage Liver Disease (MELD) 18.2 +/- 6.1. The intervention group consisted of 11 men and 3 women, BMI 28.6 +/- 5.4 kg/m(2) and MELD 18 +/- 4.5. The presence or absence of ascites was identified in the first patient evaluation and after three months. We evaluated maximal inspiratory pressure (MIP) and maximal expiratory pressure, spirometry, root mean square (RMS) of diaphragm and rectus abdominis, and the quality of life. The exercises were performed daily by patients at home for three months and were supervised at distance monthly. The manual consisted of diaphragmatic breathing exercises, diaphragmatic isometric exercise, Threshold IMT((r)), lifting upper limbs with a bat and strengthening the abdomen. RESULTS: There was significant difference (P = 0.01) between the first (initial) and the third month (final) MIP in the control group and in the intervention group, but there was no difference (P = 0.45) between the groups. The RMS of the diaphragm was lower (P = 0.001) and the functional capacity was higher (P = 0.006) in the intervention group compared to the control. The general health and mental health domains received higher scores after three months in the control group (P = 0.01) and the intervention group (P = 0.004), but there was no significant difference between them. The comparison between the presence of initial ascites with the presence of ascites was performed after three months in the control group (P = 0.083) and intervention group (P = 0.31). There was no significant difference, in relation to the presence of ascites after three months between groups (P = 0.21). In the intervention group, patients with ascites at the end of the time period had decreased scores on the social aspects SF-36 domain (P = 0.023) compared to those who had no ascites. CONCLUSION: The proposed exercises provide an increase in the inspiratory muscle strength and improve functional capacity, consequently bettering the quality of life of liver disease patients. PMID- 27358790 TI - Islet autotransplantation in a patient with hypercoagulable disorder. AB - Total pancreatectomy and islet auto transplantation is a good option for chronic pancreatitis patients who suffer from significant pain, poor quality of life, and the potential of type 3C diabetes and pancreatic cancer. Portal vein thrombosis is the most feared complication of the surgery and chances are increased if the patient has a hypercoagulable disorder. We present a challenging case of islet auto transplantation from our institution. A 29-year-old woman with plasminogen activator inhibitor-4G/4G variant and a clinical history of venous thrombosis was successfully managed with a precise peri- and post-operative anticoagulation protocol. In this paper we discuss the anti-coagulation protocol for safely and successfully caring out islet transplantation and associated risks and benefits. PMID- 27358791 TI - Acute bacterial sternoclavicular osteomyelitis in a long-term renal transplant recipient. AB - Kidney transplantation is the treatment of choice for a significant number of patients with end-stage renal disease. Although immunosuppression therapy improves graft and patient's survival, it is a major risk factor for infection following kidney transplantation altering clinical manifestations of the infectious diseases and complicating both the diagnosis and management of renal transplant recipients (RTRs). Existing literature is very limited regarding osteomyelitis in RTRs. Sternoclavicular osteomyelitis is rare and has been mainly reported after contiguous spread of infection or direct traumatic seeding of the bacteria. We present an interesting case of acute, bacterial sternoclavicular osteomyelitis in a long-term RTR. Blood cultures were positive for Streptococcus mitis, while the portal entry site was not identified. Magnetic resonance imaging of the sternoclavicluar region and a three-phase bone scan were positive for sternoclavicular osteomyelitis. Eventually, the patient was successfully treated with Daptomycin as monotherapy. In the presence of immunosuppression, the transplant physician should always remain alert for opportunistic pathogens or unusual location of osteomyelitis. PMID- 27358792 TI - Cavitary lung lesion 6 years after renal transplantation. AB - The differential diagnoses of a cavitary lung lesion in renal transplant recipients would include infection, malignancy and less commonly inflammatory diseases. Bacterial infection, Tuberculosis, Nocardiosis, fungal infections like Aspergillosis and Cryptococcosis need to be considered in these patients. Pulmonary cryptococcosis usually presents 16-21 mo after transplantation, more frequently in patients who have a high level of cumulative immunosuppression. Here we discuss an interesting patient who never received any induction/anti rejection therapy but developed both BK virus nephropathy as well as severe pulmonary Cryptococcal infection after remaining stable for 6 years after transplantation. This case highlights the risk of serious opportunistic infections even in apparently low immunologic risk transplant recipients many years after transplantation. PMID- 27358793 TI - The importance of post-partum family planning. PMID- 27358794 TI - Knowing how many children to find is the first step in finding them. PMID- 27358795 TI - Attrition from HIV care among adolescents and adults in a low-income setting. PMID- 27358796 TI - Sparks creating light? Strengthening peripheral disease surveillance in the Democratic Republic of Congo. AB - SETTING: The Democratic Republic of Congo suffers from an amalgam of disease outbreaks and other medical emergencies. An efficient response to these relies strongly on the national surveillance system. The Pool d'Urgence Congo (PUC, Congo Emergency Team) of Medecins Sans Frontieres is a project that responds to emergencies in highly remote areas through short-term vertical interventions, during which it uses the opportunity of its presence to reinforce the local surveillance system. OBJECTIVE: To investigate whether the ancillary strengthening of the peripheral surveillance system during short-term interventions leads to improved disease notification. DESIGN: A descriptive paired study measuring disease notification before and after 12 PUC interventions in 2013-2014. RESULTS: A significant increase in disease notification was observed after seven mass-vaccination campaigns and was sustained over 6 months. For the remaining five smaller-scaled interventions, no significant effects were observed. CONCLUSION: The observed improvements after even short-term interventions underline, on the one hand, how external emergency actors can positively affect the system through their punctuated actions, and, on the other hand, the dire need for investment in surveillance at peripheral level. PMID- 27358797 TI - Managing and monitoring chronic non-communicable diseases in a primary health care clinic, Lilongwe, Malawi. AB - SETTING: Patients with chronic non-communicable diseases attending a primary health care centre, Lilongwe, Malawi. OBJECTIVE: Using an electronic medical record monitoring system, to describe the quarterly and cumulative disease burden, management and outcomes of patients registered between March 2014 and June 2015. DESIGN: A cross-sectional study. RESULTS: Of 1135 patients, with new registrations increasing each quarter, 66% were female, 21% were aged ?65 years, 20% were obese, 53% had hypertension alone, 18% had diabetes alone, 12% had asthma, 10% had epilepsy and 7% had both hypertension and diabetes. In every quarter, about 30% of patients did not attend the clinic and 19% were registered as lost to follow-up (not seen for ?1 year) in the last quarter. Of those attending, over 90% were prescribed medication, and 80-90% with hypertension and/or diabetes had blood pressure/blood glucose measured. Over 85% of those with epilepsy had no seizures and 60-75% with asthma had no severe attacks. Control of blood pressure (41-51%) and diabetes (15-38%) was poor. CONCLUSION: It is feasible to manage patients with non-communicable diseases in a primary health care setting in Malawi, although more attention is needed to improve clinic attendance and the control of hypertension and diabetes. PMID- 27358798 TI - The burden of road traffic injuries in an emergency department in Addis Ababa, Ethiopia. AB - SETTING: The emergency department (ED) of Zewditu Memorial Hospital, Addis Ababa, Ethiopia. OBJECTIVE: To document the proportion, trend, characteristics and outcomes of road traffic injury (RTI) related ED admissions (?15 years) between 2014 and 2015. DESIGN: A retrospective, cross-sectional study using routinely collected ED data. RESULTS: Of 10 007 ED admissions, 779 (8%) were RTI cases; this proportion peaked in the month of January (11%). Medical records were available for 522 (67%) of these RTI cases. The median age was 28 years and 69% were males. The majority were pedestrians (69%) injured by an automobile (78%). On triage, 32% were classified as needing urgent/immediate intervention. Head injuries (20%) were the second most common injury after lower limb injuries (36%). ED outcomes were as follows: discharged (68%), hospitalised (17%), referred (17%) and died (1%). Among the 78 hospitalised cases, respectively 62% and 16% were admitted to the surgical and orthopaedic departments. Of 146 RTI cases with head injuries, 25% were hospitalised, of whom 82% were admitted to the surgical department. CONCLUSION: Our findings can guide policy makers in referral hospitals in improving the planning of hospital resources and the prioritisation of public health needs linked to further urban development. A comprehensive plan to prevent RTIs, particularly among pedestrians in Addis Ababa, is urgently needed. PMID- 27358799 TI - Caesarean sections in rural Burundi: how well are mothers doing two years on? AB - SETTING: A caesarean section (C-section) is a life-saving emergency intervention. Avoiding pregnancies for at least 24 months after a C-section is important to prevent uterine rupture and maternal death. OBJECTIVES: Two years following an emergency C-section, in rural Burundi, we assessed complications and maternal death during the post-natal period, uptake and compliance with family planning, subsequent pregnancies and their maternal and neonatal outcomes. METHODS: A household survey among women who underwent C-sections. RESULTS: Of 156 women who underwent a C-section, 116 (74%) were traced; 1 had died of cholera, 8 had migrated and 31 were untraceable. Of the 116 traced, there were no post-operative complications and no deaths. At hospital discharge, 83 (72%) women accepted family planning. At 24 months after hospital discharge (n = 116), 23 (20%) had delivered and 17 (15%) were pregnant. Of the remaining 76 women, 48 (63%) were not on family planning. The main reasons for this were religion or husband's non agreement. Of the 23 women who delivered, there was one uterine rupture, no maternal deaths and three stillbirths. CONCLUSIONS: Despite encouraging maternal outcomes, this study raises concerns around the effectiveness of current approaches to promote and sustain family planning for a minimum of 24 months following a C-section. Innovative ways of promoting family planning in this vulnerable group are urgently needed. PMID- 27358800 TI - Improving the quality of care of children in community clinics: an intervention and evaluation in Bangladesh. AB - SETTING: Community health care providers (CHCPs) in 40 rural community clinics of Comilla district, Bangladesh, were trained using a newly developed case management job aid based on the World Health Organization Integrated Management of Childhood Illness and a communication guide. OBJECTIVES: To assess 1) the change in knowledge of the CHCPs after training; 2) the absolute quality of care provided by the CHCPs (determined as the proportion of children aged <5 years [under-fives] correctly diagnosed, treated and referred); and 3) the consultation behaviour of the CHCPs. DESIGN: Change in knowledge was assessed by tests pre-and post-training. The quality of care was determined by reassessments at the clinic exit by a medical officer, without a baseline comparison. Consultation behaviour was assessed through direct observation. The study was performed during 2014 2015. RESULTS: The mean standard knowledge score of the CH-CPs increased from 19 to 25 (P < 0.001). Of 1490 under-fives examined, 91% were correctly diagnosed, 86% were correctly treated and 99.5% received a correct referral decision. The CHCPs performed well on most of the measures of good communication, although one third did not explain the diagnosis and treatment to patients. CONCLUSION: The training was effective in changing knowledge. The CHCPs applied the knowledge gained and provided good quality care. Following these results, the Bangladesh Ministry of Health and Family Welfare has scaled up the training nationwide. The lessons learnt should be useful for other countries. PMID- 27358801 TI - Two methods for setting child-focused tuberculosis care targets. AB - OBJECTIVE: To allocate resources for household contact investigations, tuberculosis (TB) programs need estimates of the numbers of child contacts requiring care. DESIGN: We developed two methods to estimate annual numbers of child contacts aged 0-14 years requiring evaluation and treatment. Method 1 combines local data using simple formulas. Using publicly available data, Method 2 uses a linear regression model based on Demographic and Health Survey and World Bank data to estimate the number of children per household, then combines these results with case notifications and risk estimates of disease and infection. RESULTS: Applying Method 1 to data from Malawi indicated that every year ~21 000 child contacts require evaluation and ~1900 should be diagnosed with TB. Applying Method 2 to all countries suggested that, globally, 2.41 million (95% uncertainty interval [UI] 2.36-2.46) children aged <5 years, and 5.07 million (95%UI 4.81 5.34) children aged 5-14 years live in households of adult patients with known TB. Of these, 239 014 (95%UI 118 649-478581) and 419 816 (95%UI 140600-1 268805), respectively, will have TB. An additional 848 453 (95%UI 705838-1 017551) and 2660 885 (95%UI 2080517-3 413 189), respectively, will be infected. CONCLUSION: It is feasible to use available data to set programmatic evaluation and treatment targets to improve care for child contacts of patients with TB. PMID- 27358802 TI - Outcomes of antiretroviral therapy among younger versus older adolescents and adults in an urban clinic, Zimbabwe. AB - SETTING: A non-governmental organisation-supported clinic offering health services including antiretroviral therapy (ART). OBJECTIVE: To compare ART retention between younger (age 10-14 years) vs. older (age 15-19 years) adolescents and younger (age 20-29 years) vs. older (age ?30 years) adults and determine adolescent- and adult-specific attrition-associated factors among those initiated on ART between 2010 and 2011. DESIGN: Retrospective cohort study. RESULTS: Of 110 (7%) adolescents and 1484 (93%) adults included in the study, no differences in retention were observed between younger vs. older adolescents at 6, 12 and 24 months. More younger adolescents were initiated with body mass index <16 kg/m(2) compared with older adolescents (64% vs. 47%; P = 0.04). There were more females (74% vs. 52%, P < 0.001) and fewer patients initiating ART with CD4 count ?350 cells/mm(3) (77% vs. 81%, P = 0.007) among younger vs. older adults. Younger adults demonstrated more attrition than older adults at all time-points. No attrition risk factors were observed among adolescents. Attrition-associated factors among adults included being younger, having a lower CD4 count and advanced human immunodeficiency virus disease at initiation, and initiation on a stavudine-based regimen. CONCLUSION: Younger adults demonstrated greater attrition and may require more attention. We were unable to demonstrate differences in attrition among younger vs. older adolescents. Loss to follow-up was the main reason for attrition across all age groups. Overall, earlier presentation for ART care appears important for improved ART retention among adults. PMID- 27358803 TI - High mortality in tuberculosis patients despite HIV interventions in Swaziland. AB - SETTING: All health facilities providing tuberculosis (TB) care in Swaziland. OBJECTIVE: To describe the impact of human immunodeficiency virus (HIV) interventions on the trend of TB treatment outcomes during 2010-2013 in Swaziland; and to describe the evolution in TB case notification, the uptake of HIV testing, antiretroviral therapy (ART) and cotrimoxazole preventive therapy (CPT), and the proportion of TB-HIV co-infected patients with adverse treatment outcomes, including mortality, loss to follow-up and treatment failure. DESIGN: A retrospective descriptive study using aggregated national TB programme data. RESULTS: Between 2010 and 2013, TB case notifications in Swaziland decreased by 40%, HIV testing increased from 86% to 96%, CPT uptake increased from 93% to 99% and ART uptake among TB patients increased from 35% to 75%. The TB-HIV co infection rate remained around 70% and the proportion of TB-HIV cases with adverse outcomes decreased from 36% to 30%. Mortality remained high, at 14-16%, over the study period, and anti-tuberculosis treatment failure rates were stable over time (<5%). CONCLUSION: Despite high CPT and ART uptake in TB-HIV patients, mortality remained high. Further studies are required to better define high-risk patient groups, understand the reasons for death and design appropriate interventions. PMID- 27358804 TI - Timing of antiretroviral therapy and TB treatment outcomes in patients with TB HIV in Myanmar. AB - SETTING: Integrated HIV Care programme, Mandalay, Myanmar. OBJECTIVES: To determine time to starting antiretroviral treatment (ART) in relation to anti tuberculosis treatment (ATT) and its association with TB treatment outcomes in patients co-infected with tuberculosis (TB) and the human immunodeficiency virus (HIV) enrolled from 2011 to 2014. DESIGN: Retrospective cohort study. RESULTS: Of 1708 TB-HIV patients, 1565 (92%) started ATT first and 143 (8%) started ART first. Treatment outcomes were missing for 226 patients and were thus not included. In those starting ATT first, the median time to starting ART was 8.6 weeks. ART was initiated after 8 weeks in 830 (53%) patients. Unsuccessful outcome was found in 7%, with anaemia being an independent predictor. In patients starting ART first, the median time to starting ATT was 21.6 weeks. ATT was initiated within 3 months in 56 (39%) patients. Unsuccessful outcome was found in 12%, and in 20% of those starting ATT within 3 months. Patients with CD4 count <100/mm(3) had a four times higher risk of an unsuccessful outcome. CONCLUSIONS: Timing of ART in relation to ATT was not an independent risk factor for unsuccessful outcome. Extensive screening for TB with rapid and sensitive diagnostic tests in HIV-infected persons and close monitoring of anaemia and immunosuppression are recommended to further improve TB treatment outcomes among patients with TB-HIV. PMID- 27358805 TI - 'Transfer out' tuberculosis patients: treatment outcomes after cross-checking registers, 2012-2013, Lusaka, Zambia. AB - SETTING: Lusaka, Zambia. OBJECTIVE: To assess the actual treatment outcomes of 'transfer out' (TO) cases at a diagnostic centre in Lusaka, in the third and fourth quarters of 2012, and to see the impact of this cross-check in treatment success rates (TSR) in 2013 and early 2014. DESIGN AND METHOD: In this retrospective cohort study, treatment outcomes for new bacteriologically positive tuberculosis (TB) cases referred from the diagnostic centre were reviewed and compared with those at the receiving treatment units. RESULTS: Of 49 (58%) cases referred to three treatment units, the treatment outcomes of nine had to be updated at the diagnostic centre, which reduced the proportion of TO cases from 17.6% to 11.8% and increased the TSR to 70.6% from 64.7%. CONCLUSION: The review and cross-checking of the TB registers at the diagnostic and treatment units led to a significant reduction in non-assessed cases, suggesting that the TB registers in the diagnostic and treatment units should be cross-checked regularly. There is also need for a complementary intervention to reduce the proportion of TOs associated with high loss to follow-up and non-evaluated TO rates. PMID- 27358806 TI - Diagnosis and treatment of TB patients with rifampicin resistance detected using Xpert((r)) MTB/RIF in Zimbabwe. AB - SETTING: In Zimbabwe, there are concerns about the management of tuberculosis (TB) patients with rifampicin (RMP) resistance diagnosed using Xpert((r)) MTB/RIF. OBJECTIVE: To assess linkages between diagnosis and treatment for these patients in Harare and Manicaland provinces in 2014. DESIGN: A retrospective cohort study. RESULTS: Of 20 329 Xpert assays conducted, 90% were successful, 11% detected Mycobacterium tuberculosis and 4.5% showed RMP resistance. Of 77 patients with RMP-resistant TB diagnosed by Xpert, 70% had samples sent to the reference laboratory for culture and drug susceptibility testing (CDST); 53% of the samples arrived. In 21% the samples showed M. tuberculosis growth, and in 17% the DST results were recorded, all of which confirmed RMP resistance. Of the 77 patients, 34 (44%) never started treatment for multidrug-resistant (MDR) TB, with documented reasons being death, loss to follow-up and incorrect treatment. Of the 43 patients who started MDR-TB treatment, 12 (71%) in Harare and 17 (65%) in Manicaland started within 2 weeks of diagnosis. CONCLUSION: Xpert has been rolled out successfully in two Zimbabwe provinces. However, the process of confirming CDST for Xpert-diagnosed RMP-resistant TB works poorly, and many patients are either delayed or never initiate MDR-TB treatment. These shortfalls must be addressed at the programmatic level. PMID- 27358807 TI - Mixed impact of Xpert((r)) MTB/RIF on tuberculosis diagnosis in Cambodia. AB - SETTING: National Tuberculosis (TB) Program sites in northwest Cambodia. OBJECTIVE: To evaluate the impact of Xpert((r)) MTB/RIF at point of care (POC) as compared to non-POC sites on the diagnostic evaluation of people living with the human immunodeficiency virus (PLHIV) with TB symptoms and patients with possible multidrug-resistant (MDR) TB. DESIGN: Observational cohort of patients undergoing routine diagnostic evaluation for TB following the rollout of Xpert. RESULTS: Between October 2011 and June 2013, 431 of 822 (52%) PLHIV with TB symptoms and 240/493 (49%) patients with possible MDR-TB underwent Xpert. Xpert was more likely to be performed when available as POC. A smaller proportion of PLHIV at POC sites were diagnosed with TB than at non-POC sites; however, at POC sites, a higher proportion of those diagnosed with TB were bacteriologically positive. There was poor agreement between Xpert and other tests such as smear microscopy and culture. Overall, the evaluation of patients with possible MDR-TB increased following Xpert rollout, yet for patients confirmed as having drug resistance on drug susceptibility testing, only 46% had rifampin resistance that would be identified with Xpert. CONCLUSION: Although utilization of Xpert was low, it may have contributed to an increase in evaluations for possible MDR-TB and a decline in empiric treatment for PLHIV when available as POC. PMID- 27358808 TI - Yield of intensified tuberculosis case-finding activities using Xpert((r)) MTB/RIF among risk groups in Nepal. AB - SETTING: Twenty-two districts of Nepal, where intensified case-finding (ICF) activities for tuberculosis (TB) were implemented among risk groups under the TB REACH initiative in collaboration with the National TB Programme from July 2013 to November 2015. OBJECTIVES: To assess the yield of TB screening using an algorithm with smear microscopy followed by Xpert((r)) MTB/RIF. DESIGN: A descriptive study using routinely collected data. RESULTS: Of 145 679 individuals screened, 28 574 (19.6%) had presumptive TB; 1239 (4.3%) of these were diagnosed with TB and 1195 (96%) were initiated on anti-tuberculosis treatment. The yield of screening was highest among people living with the human immunodeficiency virus (PLHIV) (6.1%), followed by household contacts (3.5%) and urban slum dwellers (0.5%). Among other risk groups, such as prisoners, factory workers, refugees and individuals with diabetes, the yield was less than 0.5%. The number needed to screen to diagnose an active TB case was 17 for PLHIV, 29 for household contacts and 197 for urban slum dwellers. Of 11 525 patients from ICF and the routine programme, 112 (1%) were diagnosed with multidrug-resistant TB. CONCLUSION: There was a substantial yield of TB cases among risk groups such as PLHIV and household contacts. Although the yield in urban slum dwellers was found to be moderate, some intervention should nonetheless be targeted because of the large population and poor access to care in this group. PMID- 27358809 TI - Implementing intensified tuberculosis case-finding among street-connected youth and young adults in Kenya. AB - BACKGROUND: Street-connected youth and young adults (SCY) suffer a myriad of health problems. In Kenya, SCY are at high risk for tuberculosis (TB) due to their congregate living situations. TB screening is not routinely implemented in SCY and there has been no published literature on the burden of TB in SCY in western Kenya. PROGRAM DESCRIPTION: In 2011, the AMPATH TB Program, an experienced TB screening program, partnered with the Tumaini Center, a trusted street youth organization, to conduct intensified case finding (ICF) for pulmonary TB among SCY. Our program aimed to investigate the numbers of SCY who reported symptoms and those diagnosed with smear-positive pulmonary TB, and link SCY with TB to treatment. RESULTS: Of 116 SCY who were screened, 114 (98%) had a positive questionnaire; 104 (90%) provided a spot sputum sample, 39 (34%) provided a morning sputum sample, and 111 (97%) reported cough of >2 weeks. One street youth tested smear-positive for TB and was treated through to cure. CONCLUSIONS: Implementing TB ICF is feasible in low-resource settings through unique collaborations between health care programs and community-based organizations. In addition to identifying smear-positive TB, our program uncovered a high burden of respiratory symptoms among SCY in Eldoret, Kenya. PMID- 27358810 TI - Food assistance to tuberculosis patients: lessons from Afghanistan. AB - Poverty, food insecurity and poor nutrition in the population are important contributors to the burden of tuberculosis (TB). For poor and food-insecure individuals, accessing and successfully completing anti-tuberculosis treatment over an extended period of time is challenging. Food and nutritional support as an incentive and enabler is employed by national TB control programmes (NTPs) worldwide as a means to encourage treatment initiation and adherence and to improve the nutritional status of patients with TB. It also offers a safety net for food-insecure households affected by TB to mitigate the financial consequences of the disease. This paper reports on the primary lessons from the review of the World Food Programme's (WFP's) Food Assistance Programme for TB patients in Afghanistan. It aims to inform the design, implementation and scale up of TB programmes in settings where food insecurity and malnutrition are prevalent. It also documents qualitative findings that suggest that patients, their families and providers viewed food support as an important asset and an essential element of the national TB control strategy. While the impact on treatment success or case detection could not be quantified, it is likely that the WFP intervention had a positive impact on the patients and their households, therefore contributing to the success of the DOTS-based NTP. PMID- 27358811 TI - Engaging private providers and Ayurvedic practitioners in Bilaspur, India: did it increase TB case detection? AB - To find 'missing' tuberculosis (TB) cases, in November 2014 we trained private practitioners (PPs) and Ayurvedic practitioners (APs; Indian system of medicine) in Bilaspur district, India, to identify patients with presumptive TB and refer them to sputum microscopy centres. To reinforce this training, we sent weekly text message reminders during January-March 2015. All 50 APs and 23 of 29 PPs participated. The number of patients with presumptive TB referred by the PPs and APs increased from 38 (January-March 2014) to 104 (January-March 2015), and the number of smear-positive TB patients diagnosed increased from 5 to 16, a 220% increase. While the intervention increased the number of referrals, it did not impact case detection at district level, due to the short duration of the intervention and the non-dominant private sector. PMID- 27358812 TI - Treating all multidrug-resistant tuberculosis patients, not just bacteriologically confirmed cases. PMID- 27358813 TI - Assessment of the anterior loop of the mandibular canal: A study using cone-beam computed tomography. AB - PURPOSE: Sufficient area in the interforaminal region is required for dental implant placement, and the anterior loop of the mandibular canal is located within the limits of this area. The aim of this study was to evaluate the prevalence and extent of the anterior loop in a Brazilian sample population using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: CBCT images from 250 patients (500 hemimandibles) obtained for various clinical indications were randomly selected and evaluated to determine the presence and length of the anterior loop. The length of the anterior loop was then compared based on gender, age, and the side of the mandible. The data were analyzed using the Pearson chi square test and linear regression analysis. RESULTS: An anterior loop was identified in 41.6% of the cases, and its length ranged from 0.25 mm to 4.00 mm (mean, 1.1+/-0.8 mm). The loop had a greater mean length and was significantly more prevalent in males (p=0.014). No significant differences were found between the right and left sides regarding length (p=0.696) or prevalence (p=0.650). CONCLUSION: In this study, a high prevalence of the anterior loop of the mandibular canal was found, and although its length varied greatly, in most cases it was less than 1 mm long. Although this is a prevalent anatomical variation, safety limits for the placement of implants in this region cannot be established before an accurate evaluation using imaging techniques in order to identify and preserve the neurovascular bundles. PMID- 27358814 TI - Novel three-dimensional position analysis of the mandibular foramen in patients with skeletal class III mandibular prognathism. AB - PURPOSE: To analyze the relative position of the mandibular foramina (MnFs) in patients diagnosed with skeletal class III malocclusion. MATERIALS AND METHODS: Computed tomography (CT) images were collected from 85 patients. The vertical lengths of each anatomic point from the five horizontal planes passing through the MnF were measured at the coronoid process, sigmoid notch, condyle, and the gonion. The distance from the anterior ramus point to the posterior ramus point on the five horizontal planes was designated the anteroposterior horizontal distance of the ramus for each plane. The perpendicular distance from each anterior ramus point to each vertical plane through the MnF was designated the horizontal distance from the anterior ramus to the MnF. The horizontal and vertical positions were examined by regression analysis. RESULTS: Regression analysis showed the heights of the coronoid process, sigmoid notch, and condyle for the five horizontal planes were significantly related to the height of the MnF, with the highest significance associated with the MnF-mandibular plane (coefficients of determination (R(2)): 0.424, 0.597, and 0.604, respectively). The horizontal anteroposterior length of the ramus and the distance from the anterior ramus point to the MnF were significant by regression analysis. CONCLUSION: The relative position of the MnF was significantly related to the vertical heights of the sigmoid notch, coronoid process, and condyle as well as to the horizontal anteroposterior length of the ascending ramus. These findings should be clinically useful for patients with skeletal class III mandibular prognathism. PMID- 27358815 TI - Comparison of the diagnostic performance of panoramic and occlusal radiographs in detecting submandibular sialoliths. AB - PURPOSE: The aim of this study was to assess and compare the diagnostic performance of panoramic and occlusal radiographs in detecting submandibular sialoliths. MATERIALS AND METHODS: A total of 40 patients (20 cases and 20 controls) were included in this retrospective study. Cases were defined as subjects with a submandibular sialolith confirmed by computed tomography (CT), whereas controls did not have any submandibular calcifications. Three observers with different expertise levels assessed panoramic and occlusal radiographs of all subjects for the presence of sialoliths. Intraobserver and interobserver agreement were assessed using the kappa test. Sensitivity, specificity, accuracy, positive and negative predictive values, and the diagnostic odds ratio of panoramic and occlusal radiographs in screening for submandibular sialoliths were calculated for each observer. RESULTS: The sensitivity and specificity values for occlusal and panoramic radiographs all ranged from 80% to 100%. The lowest values of sensitivity and specificity observed among the observers were 82.6% and 80%, respectively (P=0.001). Intraobserver and interobserver agreement were higher for occlusal radiographs than for panoramic radiographs, although panoramic radiographs demonstrated a higher overall accuracy. CONCLUSION: Both panoramic and occlusal radiographic techniques displayed satisfactory diagnostic performance and should be considered before using a CT scan to detect submandibular sialoliths. PMID- 27358816 TI - The accuracy of linear measurements of maxillary and mandibular edentulous sites in cone-beam computed tomography images with different fields of view and voxel sizes under simulated clinical conditions. AB - PURPOSE: The objective of this study was to investigate the effect of varying resolutions of cone-beam computed tomography images on the accuracy of linear measurements of edentulous areas in human cadaver heads. Intact cadaver heads were used to simulate a clinical situation. MATERIALS AND METHODS: Fiduciary markers were placed in the edentulous areas of 4 intact embalmed cadaver heads. The heads were scanned with two different CBCT units using a large field of view (13 cm*16 cm) and small field of view (5 cm*8 cm) at varying voxel sizes (0.3 mm, 0.2 mm, and 0.16 mm). The ground truth was established with digital caliper measurements. The imaging measurements were then compared with caliper measurements to determine accuracy. RESULTS: The Wilcoxon signed rank test revealed no statistically significant difference between the medians of the physical measurements obtained with calipers and the medians of the CBCT measurements. A comparison of accuracy among the different imaging protocols revealed no significant differences as determined by the Friedman test. The intraclass correlation coefficient was 0.961, indicating excellent reproducibility. Inter-observer variability was determined graphically with a Bland-Altman plot and by calculating the intraclass correlation coefficient. The Bland-Altman plot indicated very good reproducibility for smaller measurements but larger discrepancies with larger measurements. CONCLUSION: The CBCT-based linear measurements in the edentulous sites using different voxel sizes and FOVs are accurate compared with the direct caliper measurements of these sites. Higher resolution CBCT images with smaller voxel size did not result in greater accuracy of the linear measurements. PMID- 27358817 TI - A dose monitoring system for dental radiography. AB - PURPOSE: The current study investigates the feasibility of a platform for a nationwide dose monitoring system for dental radiography. The essential elements for an unerring system are also assessed. MATERIALS AND METHODS: An intraoral radiographic machine with 14 X-ray generators and five sensors, 45 panoramic radiographic machines, and 23 cone-beam computed tomography (CBCT) models used in Korean dental clinics were surveyed to investigate the type of dose report. A main server for storing the dose data from each radiographic machine was prepared. The dose report transfer pathways from the radiographic machine to the main sever were constructed. An effective dose calculation method was created based on the machine specifications and the exposure parameters of three intraoral radiographic machines, five panoramic radiographic machines, and four CBCTs. A viewing system was developed for both dentists and patients to view the calculated effective dose. Each procedure and the main server were integrated into one system. RESULTS: The dose data from each type of radiographic machine was successfully transferred to the main server and converted into an effective dose. The effective dose stored in the main server is automatically connected to a viewing program for dentist and patient access. CONCLUSION: A patient radiation dose monitoring system is feasible for dental clinics. Future research in cooperation with clinicians, industry, and radiologists is needed to ensure format convertibility for an efficient dose monitoring system to monitor unexpected radiation dose. PMID- 27358818 TI - Prevalence of bony septa, antral pathology, and dimensions of the maxillary sinus from a sinus augmentation perspective: A retrospective cone-beam computed tomography study. AB - PURPOSE: Sinus elevation procedures have become a routine and reliable way to gain bone volume in the edentulous maxilla for dental implant placement. Presence of bony septations and pathology in the maxillary sinus often cause complications leading to graft or implant failure or both. The aim of this study was to retrospectively evaluate the prevalence of pathology, direction of the septa, and sinus width measured at 2 mm, 5 mm, and 10 mm from the sinus floor in maxillary sinuses using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Seventy-two sinuses from 36 random preoperative CBCT scans referred for implant therapy were retrospectively evaluated for the number, prevalence, and direction of bony septations and presence of pathology. Width of the sinus was also measured at 2 mm, 5 mm, and 10 mm from the sinus floor to account for the amount of bone available for implant placement. RESULTS: Maxillary sinus septa were found in 59.7%. Presence of a single septum was noted in 20 sinuses (27.7%), followed by two septa in 17 sinuses. The most common direction of the septum was the transverse direction. Retention pseudocyst and mucosal thickening were the most commonly seen abnormality/pathology. CONCLUSION: Based on the high prevalence of septa and sinus pathology in this sample, a preoperative CBCT scan might be helpful in minimizing complications during sinus augmentation procedures for dental implant therapy. PMID- 27358819 TI - Comparison of interradicular distances and cortical bone thickness in Thai patients with Class I and Class II skeletal patterns using cone-beam computed tomography. AB - PURPOSE: This study evaluated and compared interradicular distances and cortical bone thickness in Thai patients with Class I and Class II skeletal patterns, using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Pretreatment CBCT images of 24 Thai orthodontic patients with Class I and Class II skeletal patterns were included in the study. Three measurements were chosen for investigation: the mesiodistal distance between the roots, the width of the buccolingual alveolar process, and buccal cortical bone thickness. All distances were recorded at five different levels from the cementoenamel junction (CEJ). Descriptive statistical analysis and t-tests were performed, with the significance level for all tests set at p<0.05. RESULTS: Patients with a Class II skeletal pattern showed significantly greater maxillary mesiodistal distances (between the first and second premolars) and widths of the buccolingual alveolar process (between the first and second molars) than Class I skeletal pattern patients at 10 mm above the CEJ. The maxillary buccal cortical bone thicknesses between the second premolar and first molar at 8 mm above the CEJ in Class II patients were likewise significantly greater than in Class I patients. Patients with a Class I skeletal pattern showed significantly wider mandibular buccolingual alveolar processes than did Class II patients (between the first and second molars) at 4, 6, and 8 mm below the CEJ. CONCLUSION: In both the maxilla and mandible, the mesiodistal distances, the width of the buccolingual alveolar process, and buccal cortical bone thickness tended to increase from the CEJ to the apex in both Class I and Class II skeletal patterns. PMID- 27358820 TI - Evaluation of condylar positions in patients with temporomandibular disorders: A cone-beam computed tomographic study. AB - PURPOSE: This study was performed to compare the condylar position in patients with temporomandibular joint disorders (TMDs) and a normal group by using cone beam computed tomography (CBCT). MATERIALS AND METHODS: In the TMD group, 25 patients (5 men and 20 women) were randomly selected among the ones suffering from TMD according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). The control group consisted of 25 patients (8 men and 17 women) with normal temporomandibular joints (TMJs) who were referred to the radiology department in order to undergo CBCT scanning for implant treatment in the posterior maxilla. Linear measurements from the superior, anterior, and posterior joint spaces between the condyle and glenoid fossa were made through defined landmarks in the sagittal view. The inclination of articular eminence was also determined. RESULTS: The mean anterior joint space was 2.3 mm in the normal group and 2.8 mm in the TMD group, respectively. The results showed that there was a significant correlation between the superior and posterior joint spaces in both the normal and TMD groups, but it was only in the TMD group that the correlation coefficient among the dimensions of anterior and superior spaces was significant. There was a significant correlation between the inclination of articular eminence and the size of the superior and posterior spaces in the normal group. CONCLUSION: The average dimension of the anterior joint space was different between the two groups. CBCT could be considered a useful diagnostic imaging modality for TMD patients. PMID- 27358821 TI - The impact of reorienting cone-beam computed tomographic images in varied head positions on the coordinates of anatomical landmarks. AB - PURPOSE: The aim of this study was to compare the coordinates of anatomical landmarks on cone-beam computed tomographic (CBCT) images in varied head positions before and after reorientation using image analysis software. MATERIALS AND METHODS: CBCT images were taken in a normal position and four varied head positions using a dry skull marked with 3 points where gutta percha was fixed. In each of the five radiographic images, reference points were set, 20 anatomical landmarks were identified, and each set of coordinates was calculated. Coordinates in the images from the normally positioned head were compared with those in the images obtained from varied head positions using statistical methods. Post-reorientation coordinates calculated using a three-dimensional image analysis program were also compared to the reference coordinates. RESULTS: In the original images, statistically significant differences were found between coordinates in the normal-position and varied-position images. However, post reorientation, no statistically significant differences were found between coordinates in the normal-position and varied-position images. CONCLUSION: The changes in head position impacted the coordinates of the anatomical landmarks in three-dimensional images. However, reorientation using image analysis software allowed accurate superimposition onto the reference positions. PMID- 27358822 TI - Evaluation of canalis basilaris medianus using cone-beam computed tomography. AB - The aim of this report is to present two cases of canalis basilaris medianus as identified on cone-beam computed tomography (CBCT) in the base of the skull. The CBCT data sets were sent for radiographic consultation. In both cases, multi planar views revealed an osseous defect in the base of the skull in the clivus region, the sagittal view showed a unilateral, well-defined, non-corticated, track-like low-attenuation osseous defect in the clivus. The appearance of the defect was highly reminiscent of a fracture of the clivus. The borders of osseous defect were smooth, and no other radiographic signs suggestive of osteolytic destructive processes were noted. Based on the overall radiographic examination, a radiographic impression of canalis basilaris medianus was made. Canalis basilaris medianus is a rare anatomical variant and is generally observed on the clivus. Due to its potential association with meningitis, it should be recognized and reported to avoid potential complications. PMID- 27358823 TI - Cone-beam computed tomography usage: An alert to the field of dentistry. PMID- 27358825 TI - Epigenetic modification of long interspersed elements-1 in cumulus cells of mature and immature oocytes from patients with polycystic ovary syndrome. AB - OBJECTIVE: The long interspersed elements (LINE-1, L1s) are a group of genetic elements found in large numbers in the human genome that can translate into phenotype by controlling genes. Growing evidence supports the role of epigenetic in polycystic ovary syndrome (PCOS). The purpose of this study is to evaluate the DNA methylation levels in LINE-1 in a tissue-specific manner using cumulus cells from patients with PCOS compared with normal controls. METHODS: The study included 19 patients with PCOS and 22 control patients who were undergoing controlled ovarian hyperstimulation. After oocyte retrieval, cumulus cells were extracted. LINE-1 DNA methylation levels were analysed by bisulfite treatment, polymerase chain reaction, and restriction enzyme digestion. The Connection Up- and Down-Regulation Expression Analysis of Microarrays software package was used to compare the gene regulatory functions of intragenic LINE-1. RESULTS: The results showed higher LINE-1 DNA methylation levels in the cumulus cells of mature oocytes in PCOS patients, 79.14 (+/-2.66) vs. 75.40 (+/-4.92); p=0.004, but no difference in the methylation of cumulus cells in immature oocytes between PCOS and control patients, 70.33 (+/-4.79) vs. 67.79 (+/-5.17); p=0.155. However, LINE-1 DNA methylation levels were found to be higher in the cumulus cells of mature oocytes than in those of immature oocytes in both PCOS and control patients. CONCLUSION: These findings suggest that the epigenetic modification of LINE-1 DNA may play a role in regulating multiple gene expression that affects the pathophysiology and development of mature oocytes in PCOS. PMID- 27358826 TI - Dietary supplementation with astaxanthin may ameliorate sperm parameters and DNA integrity in streptozotocin-induced diabetic rats. AB - OBJECTIVE: Diabetes mellitus (DM) is known to cause many systemic complications as well as male infertility. Astaxanthin (ASTX) is a powerful antioxidant that is involved in a variety of biologically active processes, including those with anti diabetes effects. The present study investigates the effect of ASTX on the spermatozoa function in streptozotocin (STZ)-induced diabetic rats. METHODS: We divided 30 adult rats into three groups (10 rats per group), with a control group that received corn oil mixed with chow. DM was induced by intra-peritoneal injection of STZ. Eight weeks after the STZ injection, half of the diabetic animals were used as diabetic controls, and the rest were treated with ASTX for 56 days. Then the parameters and chromatin integrity of the epididymal sperm were analyzed using chromomycin A3, toluidine blue (TB), and acridine orange (AO) staining. RESULTS: The count, viability, and motility of the epididymal sperm were decreased significantly in the STZ group in comparison with the control group (count and viability, p<0.001; motility, p<0.001;0.01). ASTX increased normal morphology and viable spermatozoa compared to the STZ group (morphology, p=0.001; viability, p<0.001;0.05). The percentage of abnormal chromatins in TB and AO staining was higher in the STZ group compared to the control group (p<0.001;0.001). The mean percentage of TB and AO positive spermatozoa in STZ rats was significantly lower in the STZ+ASTX group (TB, p=0.001; AO, p<0.001;0.05). CONCLUSION: This study observed that in vivo ASTX treatment partially attenuates some detrimental effect of diabetes. Conversely, ASTX improved sperm viability, normal morphology, and DNA integrity. PMID- 27358827 TI - Serum and seminal plasma insulin-like growth factor-1 in male infertility. AB - OBJECTIVE: Growth hormone and its mediator, insulin-like growth factor-1 (IGF-1), have been suggested to exert gonadotropic actions in both humans and animals. The present study was conducted to assess the relationship between serum IGF-1 concentration, seminal plasma concentration, and sperm parameter abnormalities. METHODS: A total of 79 men were enrolled in this study from December 2011 to July 2012 and were prospectively analyzed. Patient parameters analyzed included age, body mass index, smoking status, urological history, and fertility history. Patients were divided into four groups based on their semen parameters: normal (A, n=31), abnormal sperm motility (B, n=12), abnormal sperm morphology (C, n=20), and two or more abnormal parameters (D, n=16). Patient seminal plasma and serum IGF-1 concentrations were determined. RESULTS: Patient baseline characteristics were not significantly different between any of the groups. The serum IGF-1 levels in groups B, C, and D were significantly lower than the levels in group A; however, the seminal plasma IGF-1 levels were not significantly different between any of the groups. CONCLUSION: Men with abnormal sperm parameters had significantly lower levels of serum IGF-1 compared with men with normal sperm parameters. Seminal plasma IGF-1 levels, however, did not differ significantly between the groups investigated here. Further investigations will be required to determine the exact mechanisms by which growth hormone and IGF-1 affect sperm quality. PMID- 27358828 TI - Evidence for obtaining a second successive semen sample for intrauterine insemination in selected patients: results from 32 consecutive cases. AB - OBJECTIVE: The goal of this study was to compare the semen parameters of two successive samples obtained within an interval of less than 60 minutes from patients planning to undergo intrauterine insemination (IUI) whose first samples exhibited low semen quality. METHODS: Thirty-two consecutive patients were enrolled in the study. On the day of IUI, the semen analysis of the samples initially presented by all patients met at least two of the following criteria: sperm concentration <5*10(6)/mL, total sperm count <10*10(6), progressive sperm motility (a+b) in the native sample <30%, and total motile sperm count (TMSC) <4*10(6). A successive semen sample was obtained no more than 60 minutes after the first sample. RESULTS: Compared to the first sample, the second exhibited significantly (p<0.05) improved sperm concentration, TMSC, progressive motility, and vitality. Regarding TMSC, the most critical parameter on the day of IUI, 23 patients (71.8%) improved it, while nine (28.2%) displayed poorer outcomes. CONCLUSION: In defined cases, requesting a second successive ejaculate on the day of insemination may result in a high percentage of cases in an improvement of the quality of the sample. PMID- 27358829 TI - A retrospective study of single frozen-thawed blastocyst transfer. AB - OBJECTIVE: To study the clinical outcomes of single frozen-thawed blastocyst transfer cycles according to the hatching status of frozen-thawed blastocysts. METHODS: Frozen-thawed blastocysts were divided into three groups according to their hatching status as follows: less-than-expanded blastocyst (<=EdB), hatching blastocyst (HgB), and hatched blastocyst (HdB). The female age and infertility factors of each group were evaluated. The quality of the single frozen-thawed blastocyst was also graded as grade A, tightly packed inner cell mass (ICM) and many cells organized in the trophectoderm epithelium (TE); grade B, several and loose ICM and TE; and grade C, very few ICM and a few cells in the TE. The clinical pregnancy and implantation rate were compared between each group. The data were analyzed by either t-test or chi-square analysis. RESULTS: There were no statistically significant differences in average female ages, infertility factors, or the distribution of blastocyst grades A, B, and C in each group. There was no significant difference in the clinical pregnancy and implantation rate of each group according to their blastocyst grade. However, there was a significant difference in the clinical pregnancy and implantation rate between each group. In the HdB group, the clinical pregnancy and implantation rate were similar regardless of the blastocyst quality. CONCLUSION: There was an effect on the clinical outcomes depending on whether the blastocyst hatched during single frozen-thawed blastocyst transfer. When performing single frozen-thawed blastocyst transfer, the hatching status of the frozen-thawed blastocyst may be a more important parameter for clinical outcomes than the quality of the frozen thawed blastocyst. PMID- 27358824 TI - Epigenetics: A key paradigm in reproductive health. AB - It is well established that there is a heritable element of susceptibility to chronic human ailments, yet there is compelling evidence that some components of such heritability are transmitted through non-genetic factors. Due to the complexity of reproductive processes, identifying the inheritance patterns of these factors is not easy. But little doubt exists that besides the genomic backbone, a range of epigenetic cues affect our genetic programme. The inter generational transmission of epigenetic marks is believed to operate via four principal means that dramatically differ in their information content: DNA methylation, histone modifications, microRNAs and nucleosome positioning. These epigenetic signatures influence the cellular machinery through positive and negative feedback mechanisms either alone or interactively. Understanding how these mechanisms work to activate or deactivate parts of our genetic programme not only on a day-to-day basis but also over generations is an important area of reproductive health research. PMID- 27358830 TI - Nomogram to predict the number of oocytes retrieved in controlled ovarian stimulation. AB - OBJECTIVE: Ovarian reserve tests are commonly used to predict ovarian response in infertile patients undergoing ovarian stimulation. Although serum markers such as basal follicle-stimulating hormone (FSH) or random anti-Mullerian hormone (AMH) level and ultrasonographic markers (antral follicle count, AFC) are good predictors, no single test has proven to be the best predictor. In this study, we developed appropriate equations and novel nomograms to predict the number of oocytes that will be retrieved using patients' age, serum levels of basal FSH and AMH, and AFC. METHODS: We analyzed a database containing clinical and laboratory information of 141 stimulated in vitro fertilization (IVF) cycles performed at a university-based hospital between September 2009 and December 2013. We used generalized linear models for prediction of the number of oocytes. RESULTS: Age, basal serum FSH level, serum AMH level, and AFC were significantly related to the number of oocytes retrieved according to the univariate and multivariate analyses. The equations that predicted the number of oocytes retrieved (log scale) were as follows: model (1) 3.21-0.036*(age)+0.089*(AMH), model (2) 3.422 0.03*(age)-0.049*(FSH)+0.08*(AMH), model (3) 2.32-0.017*(age)+0.039*(AMH)+0. 03*(AFC), model (4) 2.584-0.015*(age)-0.035*(FSH)+0.038*(AMH)+0.026*(AFC). model 4 showed the best performance. On the basis of these variables, we developed nomograms to predict the number of oocytes that can be retrieved. CONCLUSION: Our nomograms helped predict the number of oocytes retrieved in stimulated IVF cycles. PMID- 27358831 TI - Cryopreservation of in vitro matured oocytes after ex vivo oocyte retrieval from gynecologic cancer patients undergoing radical surgery. AB - OBJECTIVE: The aim of this study was to report a case series of in vitro matured (IVM) oocyte freezing in gynecologic cancer patients undergoing radical surgery under time constraints as an option for fertility preservation (FP). METHODS: Case series report. University-based in vitro fertilization center. Six gynecologic cancer patients who were scheduled to undergo radical surgery the next day were referred for FP. The patients had endometrial (n=2), ovarian (n=3), and double primary endometrial and ovarian (n=1) cancer. Ex vivo retrieval of immature oocytes from macroscopically normal ovarian tissue was followed by mature oocyte freezing after IVM or embryo freezing with intracytoplasmic sperm injection. RESULTS: A total of 53 oocytes were retrieved from five patients, with a mean of 10.6 oocytes per patient. After IVM, a total of 36 mature oocytes were obtained, demonstrating a 67.9% maturation rate. With regard to the ovarian cancer patients, seven IVM oocytes were frozen from patient 3, who had stage IC cancer, whereas one IVM oocyte was frozen from patient 4, who had stage IV cancer despite being of a similar age. With regard to the endometrial cancer patients, 15 IVM oocytes from patient 1 were frozen. Five embryos were frozen after the fertilization of IVM oocytes from patient 6. CONCLUSION: Immature oocytes can be successfully retrieved ex vivo from macroscopically normal ovarian tissue before radical surgery. IVM oocyte freezing provides a possible FP option in patients with advanced-stage endometrial or ovarian cancer without the risk of cancer cell spillage or time delays. PMID- 27358832 TI - Application of serum anti-Mullerian hormone levels in selecting patients with polycystic ovary syndrome for in vitro maturation treatment. AB - OBJECTIVE: The purpose of this study was to identify useful clinical factors for the identification of patients with polycystic ovary syndrome (PCOS) who would benefit from in vitro maturation (IVM) treatment without exhibiting compromised pregnancy outcomes. METHODS: A retrospective cohort study was performed of 186 consecutive patients with PCOS who underwent human chorionic gonadotropin-primed IVM treatment between March 2010 and March 2014. Only the first IVM cycle of each patient was included in this study. A retrospective case-control study was subsequently conducted to compare pregnancy outcomes between IVM and conventional in vitro fertilization (IVF) cycles. RESULTS: Through logistic regression analyses, we arrived at the novel finding that serum anti-Mullerian hormone (AMH) levels and the number of fertilized oocytes in IVM were independent predictive factors for live birth with unstandardized coefficients of 0.078 (95% confidence interval [CI], 1.005-1.164; p=0.037) and 0.113 (95% CI, 1.038-1.208; p=0.003), respectively. Furthermore, these two parameters were able to discriminate patients who experienced live births from non-pregnant IVM patients using cut-off levels of 8.5 ng/mL and five fertilized oocytes, respectively. A subsequent retrospective case-control study of patients with PCOS who had serum AMH levels >=8.5 ng/mL showed that IVM had pregnancy outcomes comparable to conventional IVF, and that no cases of ovarian hyperstimulation syndrome were observed. CONCLUSION: Serum AMH levels are a useful factor for predicting pregnancy outcomes in PCOS patients before the beginning of an IVM cycle. IVM may be an alternative to conventional IVF for PCOS patients if the patients are properly selected according to predictive factors such as serum AMH levels. PMID- 27358833 TI - Reproductive outcomes of retransferring retained embryos in blastocyst transfer cycles. AB - OBJECTIVE: To determine the incidence of embryo retention (ER) in the transfer catheter following embryo transfer (ET) in blastocyst transfer and investigate whether retransferring retained embryos has an impact on reproductive outcomes in patients undergoing in vitro fertilization-ET. METHODS: We retrospectively analyzed the records of 1,131 blastocyst transfers, which comprised 223 single blastocyst transfer (SBT) and 908 double blastocyst transfer (DBT) cycles. Each SBT and DBT group was classified depending on whether ET was performed without retained embryos in the catheter during the first attempt (without-ER group) or whether any retained embryos were found following ET (ER group) for the purpose of comparing reproductive outcomes in a homogenous population. RESULTS: The overall incidence of finding retained embryos was 2.8% (32/1,131). There were no retained embryos in SBT cycles. In DBT cycles, implantation rates (30.0% vs. 26.6%), positive beta-hCG rates (57.2% vs. 56.2%), clinical pregnancy rates (45.3% vs. 46.9%), and live birth rates (38.9% vs. 43.8%) were not significantly different between the without-ER and ER groups. There were no significant differences in the mean birth weight (g) 2,928.4+/-631.8 vs. 2,948.7+/-497.8 and the mean gestational age at birth (269.3+/-17.2 days vs. 264.2+/-25.7 days). A total of nine cases of congenital birth defects were found in this study population. Eight were observed in the without-ER group and one in the ER group. CONCLUSION: Our results suggest that retransfer of retained embryos does not have any adverse impact on reproductive outcomes in blastocyst transfer cycles. Furthermore, our results support finding that SBT might be advantageous for decreasing the incidence of retained embryos in catheters. PMID- 27358834 TI - Meeting Recommended Levels of Physical Activity and Health-Related Quality of Life in Rural Adults. AB - BACKGROUND: Little is known about physical activity (PA) and health-related quality of life (HRQOL) among rural adults. The purpose of this study was to investigate the relationship between meeting recommended levels of PA and HRQOL in a rural adult population. METHODS: This study analyzed data from 6,103 rural adults 18 years of age and older participating in a 2013 survey. Respondents reporting at least 150 minutes a week of moderate-intensity (or moderate-vigorous combination) PA during the past month were categorized as meeting PA guidelines. Five health variables were used to assess HRQOL. A continuous HRQOL ability score was also created using item response theory (IRT). RESULTS: Rural adults who met recommended levels of PA were significantly more likely to report good HRQOL in adjusted models of physical health (OR: 1.99; 95% CI: 1.54-2.56), mental health (OR: 1.96; 95% CI: 1.46-2.64), inactivity health (OR: 2.14; 95% CI: 1.54-2.97), general health (OR: 1.69; 95% CI: 1.35-2.13), and healthy days (OR: 1.98; 95% CI: 1.58-2.47), compared to those who did not meet recommended levels. Furthermore, rural adults meeting recommended levels of PA also had a significantly greater HRQOL ability score (51.7 +/- 0.23, Mean +/- SE), compared to those not meeting recommended levels (48.4 +/- 0.33, p < .001). CONCLUSION: This study found that meeting recommended levels of PA increases the likelihood of reporting good HRQOL in rural adults. These results should be used to promote the current PA guidelines for improved HRQOL in rural populations. PMID- 27358835 TI - The Prevalence of Depression and Concussions in a Sample of Active North American Semi-Professional and Professional Football Players. AB - BACKGROUND: Concussive events frequently occur in high impact sports such as North American football. The long term effects of concussive events on physical and psychological wellbeing are the focus of ongoing research. The purpose of this study was to determine if concussive events increase the incidence of depression in active semi-professional and professional North American football players. METHODS: An anonymous online survey was sent to 200 players to collect the following self-reported data: position played, years played, number of concussions sustained and subsequent depressive symptoms using the Center for Epidemiologic Studies Depression (CESD-R) scale. An independent T-test was used to determine differences in the number of concussive events in those with CESD-R scores <16 vs. >=16, where scores >=16 are indicative of a depressed state. Likewise, an independent T-test was used to compare CESD-R scores between players with >=3 concussions vs. <=2. RESULTS: Individuals with a CESD-R score >=16, sustained a significantly greater number of concussions (3.8 vs. 1.6) than those who scored <16 (p < 0.001). Further analysis also revealed significantly higher CESD-R scores in players who had sustained >=3 concussions (24.0 vs. 15.6) than those with <=2 (p < 0.05). CONCLUSION: Within the parameters of this study, players that were classified as depressed had sustained significantly more concussions compared to those who were not classified as depressed. Further, multiple concussive events (>=3) appears to increase symptoms of depression. PMID- 27358836 TI - Health System Development and Performance in Korea and Japan: A Comparative Study of 2000-2013. AB - BACKGROUND: The Japanese and Korean healthcare systems are very similar and thus, they have the same problems and weaknesses. This study discusses the problems and proposes complementary solutions based on the results of a comparative analysis of conditions in the healthcare systems of the two countries. METHODS: This article presents a comparative analysis of the healthcare status of the two countries based on certain health criteria used worldwide, a literature review, and data from the Korean Ministry of Health and Welfare, Japanese Ministry of Health, Labour and Welfare, World Health Organization (WHO), World Bank, and Organization for Economic Cooperation and Development (OECD). RESULTS: The scores of the healthcare systems were calculated for quantitative comparison. The performance of the Japanese health system was the best, followed by the Korean health system. Both countries observed an increased life expectancy and decreased infant and under-five mortality rates during the last 14 years. However, lower fertility rates were found, which could lead to a decreased working population and a subsequent increase in the economic burden of governments and households. A higher alcohol consumption rate was found in Korea, which was related to the establishment of interpersonal relationships. CONCLUSION: The reform of the healthcare systems in Korea and Japan led to an increased life expectancy; concurrently, reduced fertility rates led to an increasing aging population. As a result, increasing health costs require additional measures to improve health equity and strengthen health promotion. PMID- 27358837 TI - The Influence of Witnessing Inter-parental Violence and Bullying Victimization in Involvement in Fighting among Adolescents: Evidence from a School-based Cross sectional Survey in Peru. AB - BACKGROUND: Witnessing inter-parental violence and bullying victimization is common for many children and adolescents. This study examines the role of witnessing inter-parental violence and bullying victimization in involvement in physical fighting among Peruvian adolescents. METHODS: A cross-sectional study was conducted among 1,368 randomly selected adolescents in 2015. We conducted logistic regression analyses to obtain crude and adjusted odds ratios with 95% confidence intervals for involvement in fighting among male and female adolescents. RESULTS: Among all adolescents, 35.8% had been involved in fighting in the last 12 months, 32.9% had been victim of verbal bullying and 37.9% had been the victim of physical bullying. Additionally, 39.2% and 27.8% of adolescents witnessed violence against their mother and father, respectively, at least once in their lives. Multivariate logistic regression analyses found that late adolescence, participation in economic activities, being the victim of verbal bullying, stress, and witnessing violence against the father among male adolescents, and self-rated academic performance and being the victim of physical or verbal bullying among female adolescents were associated with higher odds of being involved in fighting. CONCLUSION: Verbal bullying victimization and witnessing violence against the father in males and bullying victimization in females were associated with greater odds of adolescents being involved in fighting. Creating a non-violent environment at both home and school would be an effective strategy for reducing fighting among the adolescent population. PMID- 27358838 TI - Analysis of Insecticide-Treated Net Use by Pregnant Women: Implications for Donor Organizations. AB - BACKGROUND: The World Health Organization (WHO) recommends the use of insecticide treated nets (ITNs) for the prevention of malaria and reduction of mortality and morbidity from mosquito-borne diseases. Although many countries, including the Democratic Republic of Congo, have adopted this recommendation and distributed bed nets to their inhabitants, the percentage of the population using ITNs remains low. METHODS: This study was conducted with 400 mothers with at least one child under 5 years of age in health zones in the Bandundu province. Face-to-face interviews were conducted using structured pre-coded questionnaires. Chi-square tests and logistic regressions were calculated using the SPSS Version 21.0 software. RESULTS: Among the studied variables, education status (p = 0.013), marital status (p = 0.004), ANC utilization (p = 0.13), suffering from malaria during pregnancy (p = 0.019), and knowledge of the seriousness of malaria (p = 0.013) were significant determinants of the use of ITNs in logistic regression analyses. CONCLUSION: The results of this study indicate that the regular use of ITNs by women during pregnancy is associated with marital status, attending ANC services, and awareness of the serious nature of malaria. Therefore, education about the risk factors among populations is needed. PMID- 27358839 TI - Rapid Return of Spontaneous Respiration after General Anesthesia with Sugammadex in a Patient with Myasthenia Gravis. AB - Myasthenia gravis causes weakness and fatigue of the skeletal muscles, including respiratory muscles. When immobile surgical fields are needed, neuromuscular blocking agents (NMBAs) are often administered to block muscle activity, leading to an immobile surgical field and respiratory arrest. Acetylcholinesterase inhibitors are administered to reverse the muscle block, promoting spontaneous respiration for patient recovery. If immobile surgical fields are required in myasthenic patient operations, NMBAs should be administered. However, recovery from NMBAs using acetylcholinesterase inhibitors might be delayed in myasthenic patients due to their intake of medicines that already inhibit cholinesterase, resulting in a delay in spontaneous respiration. Sugammadex is a recently introduced medicine that reverses muscle blocks through a different mechanism from acetylcholinesterase inhibitors and can be administered to facilitate the return of spontaneous respiration in myasthenic patients. Our experience of the rapid return to spontaneous respiration of a myasthenic patient with Sugammadex is reported in this paper. PMID- 27358840 TI - Body Composition and Non-alcoholic Fatty Liver Disease. PMID- 27358841 TI - New drugs in prostate cancer. AB - The standard primary treatment for advanced prostate cancer has been hormonal therapy since the 1940s. However, prostate cancer inevitably progresses to castration-resistant prostate cancer (CRPC) after a median duration of 18 months of androgen deprivation therapy. In patients with CRPC, docetaxel has been regarded as the standard treatment. However, survival advantages of docetaxel over other treatments are slim, and the need for new agents persists. In recent years, novel agents, including abiraterone, enzalutamide, cabazitaxel, radium 223, and sipuleucel-T, have been approved for the treatment of CRPC, and more such agents based on diverse mechanisms are under investigation or evaluation. In this article, the authors reviewed the current literature on recent advances in medical treatment of prostate cancer, especially CRPC. In addition, the authors elaborated on novel drugs for prostate cancer currently undergoing investigation and their mechanisms. PMID- 27358842 TI - Relationship of age, prostate-specific antigen, and prostate volume in Indonesian men with benign prostatic hyperplasia. AB - BACKGROUND: To investigate the relationship between age, prostate specific antigen (PSA), and prostate volume (PV) in Indonesian men with histologically proven benign prostatic hyperplasia. METHODS: Data were generated from our BPH database from June 1994 until December 2013. Subjects were men with a minimum age of 40 years with chief complaint of LUTS or urinary retention, diagnosed with BPH. All patients underwent TRUS-guided prostate biopsy. Patients with PSA level >10 ng/mL were excluded from the study to exclude the possibility of occult prostate cancer. PV was measured with TRUS. Appropriate statistical tests were employed for data analysis. RESULTS: In all, 1638 patients were enrolled in our study. There was a statistically significant difference in PSA (P = 0.03) and PV (P < 0.0001) between age groups. Overall correlation between age, PSA, and PV were: i). Age and PV (r = 0.12, P < 0.0001); ii). Age and PSA (r = 0.07, P = 0.008); iii). PSA and PV (r = 0.26, P < 0.0001). Subgroup analysis in terms of indwelling catheter use versus without: i). Age 66.09 +/- 8 years versus 65.38 +/ 7.66 years (P = 0.158); ii). PSA 4.93 +/- 2.62 ng/mL versus 4.68 +/- 2.82 ng/mL (P = 0.038); iii). PV 47.58 +/- 21.33 mL versus 41.43 +/- 20.55 mL (P < 0.0001). Correlation between age, PSA, and PV in patients were similar in patients with and without indwelling catheter. CONCLUSION: In Indonesian men with biopsy-proven BPH, both PV and PSA increased with ageing. Prostate volume was significantly correlated with PSA. Even though the results were weaker, these results are consistent with results in other sets of population. The results vary between different countries and thus, ethnicities. Indonesia is a populous a sociocultural and ethnically diverse country. Therefore, aside from PSA, age, and PV, when investigating men with BPH, ethnicity may also need to be taken into account. PMID- 27358843 TI - Holmium laser enucleation of the prostate followed by high-intensity focused ultrasound treatment for patients with huge prostate adenoma and localized prostate cancer: 5-Year follow-up. AB - BACKGROUND: To evaluate the efficacy of holmium laser enucleation of the prostate (HoLEP) followed by high-intensity focused ultrasound (HIFU) for patients with huge prostate adenoma and localized prostate cancer (CaP) and compare the morbidity and efficacy results with those observed in a similar population treated only with HIFU for a follow-up period of up to 5 years. METHODS: The present retrospective study included 30 CaP patients who underwent HIFU alone and 10 patients who underwent HoLEP followed by HIFU. Selection criteria for this study were no previous treatment for CaP, aged 60 years or older, cT1c-T2N0M0, prostate volume of 30 mL or more, and a follow-up period of 5 years or more. Prostate-specific antigen (PSA) biochemical recurrence-free survival (RFS) rates and functional outcomes including complications and uroflowmetry after HIFU were compared between the HIFU monotherapy and HoLEP + HIFU groups. RESULTS: The enrolled patients had a mean age of 70.3 years and 68.8 years in the HIFU monotherapy and HoLEP + HIFU groups, respectively. The 5-year PSA biochemical RFS rates of the two groups were similar (HIFU monotherapy group: 57.2%; HoLEP + HIFU group: 67.5%). The duration of indwelling urethral catheter after HIFU significantly decreased in the HoLEP + HIFU group compared with the HIFU monotherapy group (15.5 +/- 2.7 days vs. 27.5 +/- 2.3 days, P = 0.022). In terms of functional outcomes, patients who received HoLEP + HIFU had significantly higher maximum (12 months: P = 0.015, 36 months: P = 0.014) and average (36 months: P = 0.002, 60 months: P = 0.047) flow rates than those who received HIFU monotherapy. The frequency of urethral stricture (13.3% vs. 0%), symptomatic urinary tract infection (10.0% vs. 0%), and bladder stone and urethrorectal fistula (3.3% vs. 0%) tended to be higher in the HIFU monotherapy group as compared with the HoLEP + HIFU group. CONCLUSION: The HoLEP + HIFU treatment decreases urinary catheterization time and improves post-treatment urinary status without additional morbidity. PMID- 27358844 TI - Feasibility of abiraterone acetate treatment in patients with metastatic castration-resistant prostate cancer and atrial fibrillation. AB - BACKGROUND: Abiraterone acetate (AA), a selective inhibitor of the CYP17 enzyme, demonstrated a significant improvement in the treatment of patients with metastatic castration-resistant prostate cancer. The risk of endocrine side effects, mainly an increased adrenal mineralocorticoid production, could limit its use in patients with atrial fibrillation. METHODS: We retrospectively reviewed the clinical records of 85 metastatic castration-resistant prostate cancer patients treated with AA at our institutions and identified six patients suffering from concomitant atrial fibrillation. RESULTS: In these six patients, the median duration of AA treatment was 11.5 months (range 4-22 months) with a biochemical response in three patients. No significant cardiac events were observed during the treatment. CONCLUSION: Our data suggest that AA may be safely administered in patients with atrial fibrillation. PMID- 27358845 TI - Low-density lipoprotein receptors play an important role in the inhibition of prostate cancer cell proliferation by statins. AB - BACKGROUND: There are some reports about the antitumor effects of statins in these days. Statins decrease the level of cholesterol in the blood by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Inhibition of this enzyme decreases intracellular cholesterol synthesis. Thus, the expression of low density lipoprotein receptor (LDLr) is increased to import more cholesterol from the bloodstream. In this study, we assessed the effects of statins on the proliferation of prostate cancer cells, and studied the relationship between the expression of LDLr and the effects of statins. METHODS: Simvastatin was used in the experiments. We studied the effect of simvastatin on PC-3 and LNCaP cell proliferation using the MTS assay, and evaluated the expression of LDLr after administration of simvastatin by quantitative polymerase chain reaction and Western blotting. Intracellular cholesterol levels in the prostate cancer cells were measured after administration of simvastatin. Furthermore, small interfering RNA (siRNA) was used to knockdown the gene expression of LDLr. RESULTS: In PC-3 cells, simvastatin inhibited cell proliferation. In LNCaP cells, only a high concentration of simvastatin (100MUM) inhibited cell proliferation. In LNCaP cells, the protein level of LDLr was increased by simvastatin. In PC-3 cells, the protein levels of LDLr were unregulated. In PC-3 cells, but not in LNCaP cells, intracellular cholesterol levels were significantly decreased by simvastatin. After knocking down LDLr expression by siRNA, intracellular cholesterol levels were decreased, and cell proliferation was inhibited by simvastatin in LNCaP cells. CONCLUSION: Simvastatin inhibited prostate cancer cell growth by decreasing cellular cholesterol and could be more effective in androgen independent prostate cancer, where there is loss of regulation of LDLr expression. LDLr was shown to play an important role in the statin-induced inhibition of prostate cancer cell proliferation. These results suggest that future studies evaluating the cholesterol-lowering effects of statin may lead to new approaches to the prevention and treatment of prostate cancer. PMID- 27358846 TI - Modified urethrovesical anastomosis during robot-assisted simple prostatectomy: Technique and results. AB - BACKGROUND: Despite significant developments in transurethral surgery for benign prostatic hyperplasia, simple prostatectomy remains an excellent option for patients with severely enlarged glands. The objective is to describe our results of robot-assisted simple prostatectomy (RASP) with a modified urethrovesical anastomosis (UVA). METHODS: From May 2011 to February 2014, RASP with UVA was performed in 34 patients by a single surgeon (O.C.) using the da Vinci S-HD surgical system. The UVA was performed between the bladder neck and urethral margin using the Van Velthoven technique. Demographic, perioperative, and outcome data were recorded. Complications were recorded with the Clavien-Dindo system. RESULTS: The mean (standard deviation) age was 68 years (62-74 years). The median preoperative prostate volume (interquartile range) was 117 cc (99-146 cc). Operative time was 96 minutes (78-126 minutes), estimate blood loss was 200 mL (100-300 mL), and two (5.8%) patients required a blood transfusion. No conversion to open surgery was needed. The median specimen weight on pathological examination was 76 g (58-100 g). The average hospital stay was 2.2 days (1-4 days) and average Foley catheter time was 4.6 days (4-6 days). No intraoperative complications were recorded. There were seven (20.5%) postoperative complications, most of them Clavien less than or equal to Grade II. CONCLUSION: The results of our study show that RASP with UVA is a feasible, secure, and reproducible procedure with low morbidity. Additional series with larger patient cohorts are needed to validate this approach. PMID- 27358847 TI - Diagnosis and treatment patterns of male lower urinary tract symptoms suggestive of benign prostatic hyperplasia in Murjani General Hospital, Central Kalimantan, Indonesia. AB - BACKGROUND: The aim of this study was to describe the diagnosis and treatment patterns of male lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and evaluate their appropriateness in an area without an urologist and with limited resources, such as the area covered by Murjani General Hospital, Sampit, Indonesia. METHODS: This descriptive study used data collected from medical records of patients who were diagnosed with LUTS suggestive of BPH in Murjani General Hospital between September 2013 and August 2015. RESULTS: There were 89 patients. Their mean age was 64.5 years. The most common chief complaint was inability to void (59.6%), followed by frequency (10.1%). Diagnostic evaluations such as symptom scoring (1.1%), frequency-volume chart (0%), digital rectal examination (3.4%), urinalysis (5.6%), and prostate specific antigen (0%) were used rarely or never, while renal function assessment (37.1%) and imaging of the prostate (68.5%) and upper urinary tract (65.2%) were used more often. Overall, the treatment that was administered most often was indwelling catheterization (25.8%); only 19.1% visited a urologist following a referral by the physician, although 41.6% were referred to a urologist. There were 40.4% of patients with an indication for surgery, mostly in the form of recurrent or refractory urinary retention (83.3%). In this group of patients, only 38.9% received appropriate treatment in the form of open prostatectomy by a general surgeon (16.7%) or were referred to a urologist (22.2%), while 50% of them were managed with chronic indwelling catheterization. CONCLUSION: All patients received substandard diagnostic evaluations, with a pattern of preference toward imaging studies over more basic examinations for LUTS-BPH. The high frequency of indwelling catheterization in overall and inappropriate treatment in the group of patients with an indication for surgery showed that patients received suboptimal treatment. Improvements in various aspects are required to optimize the management of LUTS suggestive of BPH in Murjani General Hospital. PMID- 27358848 TI - Change of the airway space in mandibular prognathism after bimaxillary surgery involving maxillary posterior impaction. AB - BACKGROUND: The purpose of this retrospective study was to develop a two- and three-dimensional analysis of the airway using cone-beam computed tomography (CBCT) and to determine whether the airway space would be changed in mandibular prognathism after bimaxillary surgery involving maxillary posterior impaction. METHODS: Patients requiring orthognathic surgery from 2012 to 2014 were recruited for this study. CBCT scans were obtained at three points: preoperatively (T0), immediate postoperatively (T1), and after 6 months postoperatively (T2). The nasopharynx, oropharynx, and hypopharynx were measured on the CBCT scan for each patient in a repeatable manner. With the midsagittal plane, linear measurements in the middle of each were obtained. For the CBCT, volumetric measurements of each and total airway were obtained. RESULTS: A total of 22 consecutive patients (11 men and 11 women) were included in the present study. The total volume was significantly reduced (p < .001). However, the change of the diameter and volume of the nasopharynx was not statistically significant (p = .160, p = .137, respectively). In the oropharynx, the change of both the diameter and volume showed statistical significance between preoperatively and immediate postoperatively (p < .001, p = .001, respectively) and also preoperatively and after 6 months postoperatively (p = .001, p = .010, respectively). In the hypopharynx, the change of both the diameter and volume showed statistical significance between preoperatively and immediate postoperatively (p = .001, p < .001, respectively) and also preoperatively and after 6 months postoperatively (p = .001, p < .001, respectively). CONCLUSIONS: The bimaxillary surgery involving maxillary posterior impaction can reduce the volume of airway in the patients of mandibular prognathism. Although total airway volume was reduced significantly, the changes in the volume and diameter of the nasopharynx were not statistically significant. The maxillary posterior impaction affects on the nasopharyngeal airway minimally. PMID- 27358849 TI - A new Stem Cell Investigation. PMID- 27358850 TI - Protein kinase C delta (PKCdelta) splice variant modulates senescence via hTERT in adipose-derived stem cells. AB - BACKGROUND: Adipose-derived stem cells (ADSC) were isolated and characterized from lean and obese subjects. We previously reported that distinct differences were observed in differentiating lean and obese preadipocytes. Protein kinase C delta (PKCdelta) is alternatively spliced and has important roles in apoptosis. PKCdeltaI promotes apoptosis and PKCdeltaVIII promotes survival. Our previous data indicated an increase in the survival kinase, PKCdeltaVIII in ADSC derived from an obese donor. We also determined that obese adipocytes were resistant to apoptosis. Here, we determine the relationship between a survival kinase PKCdeltaVIII and hTERT expression in adipose derived stem cells from a lean and obese subject. METHODS: We evaluated the telomerase activity and human telomerase reverse transcriptase (hTERT) expression in lean and obese ADSC. The lean and obese ADSC were purchased as cryopreserved cells from ZenBioTM (Research Triangle Park, NC, USA). Analyses were performed using PRISMTM software and analyzed using two-tailed Student's t-test. RESULTS: We observed an increase in telomerase in differentiating obese ADSC using western blot analysis. We determined the levels of hTERT splice variants. hTERT alpha+/beta+ splice variant was increased after transfected of PKCdeltaVIII. We next determined whether PKCdeltaVIII over expression affected the levels of telomerase. The results indicate an increase in telomerase with PKCdeltaVIII over-expression. CONCLUSIONS: Over-expression of PKCdeltaVIII in lean ADSC substantially increased expression of hTERT and telomerase. The decreased senescence seen in obese ADSC may in part be attributed to PKCdeltaVIII. Obese ADSC undergo lower senescence and may have increased growth potential. These results propose a larger epigenetic modification in obese ADSC compared to lean ADSC. PMID- 27358851 TI - Isolated factor V deficiency in a patient with elevated PT and aPTT during routine pre-operative laboratory screening. AB - Isolated factor V (FV) deficiency is a rare disorder with approximately 150 cases reported in the literature since 1943. Bleeding symptoms from FV deficiency vary widely. FV deficiency usually manifests early in the life. We present a 59-year old case with FV deficiency discovered during pre-operative laboratory screen. PMID- 27358852 TI - Regulation of cancer stem cells by RING finger ubiquitin ligases. AB - Like normal stem cells, cancer stem cells (CSCs) are capable of self-renewal, either by symmetric or asymmetric cell division. They have the exclusive ability to reproduce malignant tumors indefinitely, and to confer resistance in response to radiation or chemotherapy. The ubiquitin modification system plays various roles in physiology and pathology. The key component for the specificity of this system is ubiquitin ligases (E3s). Of these E3s, the majority are RING finger proteins. Many RING finger E3s, such as the Cullin1-Skp1-F-box protein (SCF) E3s, CBL, BRCA1, MDM2 and von Hippel-Lindau tumour suppressor (VHL), are crucial in the regulation of cell-cycle progression and cell differentiation. As a result, many RING finger E3s are implicated in the positive and negative regulation of CSC maintenance. This review summarizes current knowledge in this research field. PMID- 27358853 TI - Cutaneous metastasis as an initial presentation of lung adenocarcinoma with KRAS mutation: a case report and literature review. AB - Cutaneous metastasis as an initial presentation occurs in 0.8% of patients with internal malignancies, and is poorly understood in its molecular pathogenesis. We reported a case in which a 61-year-old male patient initially presented with rapidly growing skin nodule on his left chest wall, then developed dyspnea and loss of weight. Echocardiogram showed a large pericardial effusion with right ventricular collapse. PET/CT revealed moderate pleural effusion and multiple lymphadenopathies with hypermetabolic concentration of radiotracer in the lymph nodes as well as in the chest wall skin mass. Biopsy of the skin mass and pericardial/pleural fluids revealed metastatic adenocarcinoma consistent with lung primary with KRAS mutation. Palliative chemotherapy was administered without resulting in any improvement. This is the first case report to show that KRAS mutant lung adenocarcinoma can be associated with cutaneous metastasis. PMID- 27358854 TI - Recent advances and novel agents for FLT3 mutated acute myeloid leukemia. AB - Acute myeloid leukemia (AML) is a devastating hematologic malignancy that affects both older adults as well as children. Treatments available for AML largely depend on cytotoxic agents and often the only curative option is an allogeneic bone marrow transplant, an option limited to young persons and associated with high morbidity and mortality. There is an urgent need for the identification of new myeloid targets and an understanding of the key genetic mutations involved in disease progression and prognosis. One such mutation is the internal tandem duplication (ITD) in the FMS-like tyrosine kinase receptor-3 (FLT3) gene which confers an inferior outcome that is attributed to a higher relapse rate. In this review, we evaluate the FLT3-ITD mutation and discuss the recent data regarding emerging approaches using FLT3 inhibitors for the treatment of AML. PMID- 27358856 TI - Changes in CpG methylation marks differentiation of human myeloid progenitors to neutrophils. PMID- 27358855 TI - Cancer stem cells: progress and challenges in lung cancer. AB - The identification of a subpopulation of tumor cells with stem cell-like characteristics first in hematological malignancies and later in solid tumors has emerged into a novel field of cancer research. It has been proposed that this aberrant population of cells now called "cancer stem cells" (CSCs) drives tumor initiation, progression, metastasis, recurrence, and drug resistance. CSCs have been shown to have the capacity of self-renewal and multipotency. Adopting strategies from the field of stem cell research has aided in identification, localization, and targeting of CSCs in many tumors. Despite the huge progress in other solid tumors such as brain, breast, and colon cancers no substantial advancements have been made in lung cancer. This is most likely due to the current rudimentary understanding of lung stem cell hierarchy and heterogeneous nature of lung disease. In this review, we will discuss the most recent findings related to identification of normal lung stem cells and CSCs, pathways involved in regulating the development of CSCs, and the importance of the stem cell niche in development and maintenance of CSCs. Additionally, we will examine the development and feasibility of novel CSC-targeted therapeutic strategies aimed at eradicating lung CSCs. PMID- 27358857 TI - MicroRNAs as biomarkers in leukemia. AB - Current diagnostic and prognostic markers still exhibit biological limitation and seeking novel molecular biomarkers is crucial for early clinical diagnosis and in the development of novel strategies for leukemia therapy. Emerging evidence showed that dysregulated microRNAs (miRNAs) play important roles in cancer including leukemia. In this review, we summarized recent progress on the role of miRNAs in leukemia, mainly focusing on recent findings that suggest the potential of miRNAs as biomarkers for diagnosis and prognosis. Notably, the circulating miRNAs were also discussed for the fact that they can be detected in body fluids, and thus represent a novel source of promising biomarkers that may be applied to clinical settings. PMID- 27358858 TI - TNF-alpha, a good or bad factor in hematological diseases? AB - Tumor necrosis factor-alpha (TNF-alpha) is a highly pleiotropic cytokine involved in a spectrum of physiological processes that control inflammation, anti-tumor responses and homeostasis through two receptors, TNF-R1 and TNF-R2. In general, TNF-R1 mediates cytotoxicity, resistance to infection and stimulation of NF kappaB. By contrast, TNF-R2 has been implicated in proliferation of T-cell line, thymocytes and human mononuclear cells. Hematological malignancies are the types of cancer that affect normal hematopoiesis, have a speedy development, high lethal rate and until now still have no effective treatment. Several studies have shown that inflammatory cytokines play an important role in the onset and progress of these diseases. In this review, we summarize the recent studies and evaluate the positive or negative role of TNF-alpha in some hematological malignancies or diseases with a malignant tendency. PMID- 27358859 TI - Reactive oxygen species in eradicating acute myeloid leukemic stem cells. AB - Leukemic stem cells (LSCs) have been proven to drive leukemia initiation, progression and relapse, and are increasingly being used as a critical target for therapeutic intervention. As an essential feature in LSCs, reactive oxygen species (ROS) homeostasis has been extensively exploited in the past decade for targeting LSCs in acute myeloid leukemia (AML). Most, if not all, agents that show therapeutic benefits are able to alter redox status by inducing ROS, which confers selectivity in eradicating AML stem cells but sparing normal counterparts. In this review, we provide the comprehensive update of ROS generating agents in the context of their impacts on our understanding of the pathogenesis of AML and its therapy. We anticipate that further characterizing these ROS agents will help us combat against AML in the coming era of LSC targeting strategy. PMID- 27358860 TI - Cancer stem cells as a potential therapeutic target in breast cancer. AB - Cancer stem cells (CSCs) are defined as the small population of cancer cells that have stem cell properties as in hierarchically organized tumors. They are considered as the source of tumor initiation and maintenance. These cells are highly resistant to current cancer treatment and may be responsible for the disease recurrence after therapy as well. Therefore, considerable efforts have been made to elucidate the molecular and pathological properties of the CSCs to develop effective therapies targeting CSCs. A growing body of experimental evidence has revealed that therapeutic targeting CSCs may offer a new strategy for patients with breast cancer (BC). In this review, we summarized the evidence for existence of CSCs, followed by an overview of their molecular biomarkers, signaling pathways and potential therapeutic strategies to target these CSCs in BC. PMID- 27358861 TI - Regulatory factors of induced pluripotency: current status. AB - Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) through enforced expression of four transcription factors [Oct4, Sox2, Klf4, and c-Myc (OSKM)]; however, the reprogramming efficiency is extremely low. This finding raises fundamental questions about the regulators that influence the change in epigenetic stability and endowment of dedifferentiation potential during reprogramming. Identification of such regulators is critical to removing the roadblocks impeding the efficient generation of safe iPSCs and their successful translation into clinical therapies. In this review, we summarize the current progress that has been made in understanding cellular reprogramming, with an emphasis on the molecular mechanisms of epigenetic regulators in induced pluripotency. PMID- 27358862 TI - Mesenchymal stem cells in pathogenesis of myelodysplastic syndromes. AB - Myelodysplastic syndromes (MDS) are clonal malignant stem cell disorders characterized by inefficient hematopoiesis. The role of the marrow microenvironment in the pathogenesis of the disease has been controversial. Emerging evidence indicated that mesenchymal stem cells (MSC) derived from MDS patients were cytogenetically abnormal, and they showed a deficient hematopoietic supportive capacity and increased production of cytokine such as tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), interferon gamma (IFN-gamma). From the point of some evidence, the abnormal microenvironment seems to participate in the progression of the disease by contributing to the selective expansion of the malignant clone. In this review, we will discuss the most recent progress related to identification of normal MSC and the importance of the stem cell niche in development and maintenance of MDS. PMID- 27358864 TI - The role of mesenchymal stem/progenitor cells in sarcoma: update and dispute. AB - Sarcoma is the collective name for a relatively rare, yet heterogeneous group of cancers, most probably derived from mesenchymal tissues. There are currently over 50 sarcoma subtypes described underscoring the clinical and biologic diversity of this group of malignant cancers. This wide lineage range might suggest that sarcomas originate from either many committed different cell types or from a multipotent cell. Mesenchymal stem/progenitor cells (MSCs) are able to differentiate into many cell types and these multipotent cells have been isolated from several adult human tumors, making them available for research as well as potential beneficial therapeutical agents. Recent accomplishments in the field have broadened our knowledge of MSCs in relation to sarcoma origin and sarcoma treatment in therapeutic settings. However, numerous concerns and disputes have been raised about whether they are the putative originating cells of sarcoma and their questionable role in sarcomagenesis and progression. We summarize the update and dispute about MSC investigations in sarcomas including the definition, cell origin hypothesis, functional and descriptive assays, roles in sarcomagenesis and targeted therapy, with the purpose to give a comprehensive view of the role of MSCs in sarcomas. PMID- 27358863 TI - Reverse transcriptase and intron number evolution. AB - BACKGROUND: Introns are universal in eukaryotic genomes and play important roles in transcriptional regulation, mRNA export to the cytoplasm, nonsense-mediated decay as both a regulatory and a splicing quality control mechanism, R-loop avoidance, alternative splicing, chromatin structure, and evolution by exon shuffling. METHODS: Sixteen complete fungal genomes were used 13 of which were sequenced and annotated by JGI. Ustilago maydis, Cryptococcus neoformans, and Coprinus cinereus (also named Coprinopsis cinerea) were from the Broad Institute. Gene models from JGI-annotated genomes were taken from the GeneCatalog track that contained the best representative gene models. Varying fractions of the GeneCatalog were manually curated by external users. For clarity, we used the JGI unique database identifier. RESULTS: The last common ancestor of eukaryotes (LECA) has an estimated 6.4 coding exons per gene (EPG) and evolved into the diverse eukaryotic life forms, which is recapitulated by the development of a stem cell. We found a parallel between the simulated reverse transcriptase (RT) mediated intron loss and the comparative analysis of 16 fungal genomes that spanned a wide range of intron density. Although footprints of RT (RTF) were dynamic, relative intron location (RIL) to the 5'-end of mRNA faithfully traced RT-mediated intron loss and revealed 7.7 EPG for LECA. The mode of exon length distribution was conserved in simulated intron loss, which was exemplified by the shared mode of 75 nt between fungal and Chlamydomonas genomes. The dominant ancient exon length was corroborated by the average exon length of the most intron-rich genes in fungal genomes and consistent with ancient protein modules being ~25 aa. Combined with the conservation of a protein length of 400 aa, the earliest ancestor of eukaryotes could have 16 EPG. During earlier evolution, Ascomycota's ancestor had significantly more 3'-biased RT-mediated intron loss that was followed by dramatic RTF loss. There was a down trend of EPG from more conserved to less conserved genes. Moreover, species-specific genes have higher exon-densities, shorter exons, and longer introns when compared to genes conserved at the phylum level. However, intron length in species-specific genes became shorter than that of genes conserved in all species after genomes experiencing drastic intron loss. The estimated EPG from the most frequent exon length is more than double that from the RIL method. CONCLUSIONS: This implies significant intron loss during the very early period of eukaryotic evolution. De novo gene-birth contributes to shorter exons, longer introns, and higher exon density in species-specific genes relative to conserved genes. PMID- 27358865 TI - Interleukin 8/KC enhances G-CSF induced hematopoietic stem/progenitor cell mobilization in Fancg deficient mice. AB - BACKGROUND: Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by a progressive bone marrow aplasia, chromosomal instability, and acquisition of malignancies. Successful hematopoietic cell transplantation (HCT) for FA patients is challenging due to hypersensitivity to DNA alkylating agents and irradiation of FA patients. Early mobilization of autologous stem cells from the bone marrow has been thought to be ideal prior to the onset of bone marrow failure, which often occurs during childhood. However, the markedly decreased response of FA hematopoietic stem cells to granulocyte colony-stimulating factor (G-CSF) is circumventive of this autologous HCT approach. To-date, the mechanism for defective stem cell mobilization in G-CSF treated FA patients remains unclear. METHODS: Fancg heterozygous (Fancg (+/-)) mice utilized in these studies. Student's t-test and one-way ANOVA were used to evaluate statistical differences between WT and Fancg (-/-) cells. Statistical significance was defined as P values less than 0.05. RESULTS: Fancg deficient (Fancg (-/-)) mesenchymal stem/progenitor cells (MSPCs) produce significant lower levels of KC, an interleukin-8 (IL-8) related chemoattractant protein in rodents, as compared to wild type cells. Combinatorial administration of KC and G-CSF significantly increased the mobilization of hematopoietic stem/progenitor cells (HSPCs) in Fancg (-/-) mice. CONCLUSIONS: In summary, our results suggest that KC/IL-8 could be proved useful in the synergistic mobilization of FA HSPCs in combination with G-CSF. PMID- 27358866 TI - Targeting cancer stem cells with oncolytic virus. AB - Cancer stem cells (CSCs) represent a distinct subpopulation of cancer cells which are shown to be relatively resistant to conventional anticancer therapies and have been correlated to disease recurrence. Oncolytic viruses utilize methods of cell killing that differ from traditional therapies and thus are able to elude the typical mechanisms that CSCs use to resist current chemotherapies and radiotherapies. Moreover, genetically engineered oncolytic viruses may further augment the oncolytic effects. Here we review the recent data regarding the ability of several oncolytic viruses to eradicate CSCs. PMID- 27358867 TI - Multiple myeloma with leptomeningeal involvement and positive CSF. PMID- 27358869 TI - Franklin's disease: immunoglobulin heavy chain disease. PMID- 27358868 TI - Oncolytic virus as a cancer stem cell killer: progress and challenges. AB - Oncolytic viruses (OVs), which were discovered more than one century ago, have been used in multiple clinical trials for cancer therapy. OVs specifically target cancer cells when sparing normal cells by exploiting biochemical differences between normal and tumor cells. Hence oncolytic virotherapy is more specific at targeting cancer cells compared with conventional anti-cancer therapy. Apart from the lack of specificity, conventional anti-cancer therapies also often witness relapse and incomplete cure of cancer. One hypothesis explaining this phenomenon is that a subpopulation of cancer cells, known as cancer stem cells (CSCs), are resistant to conventional therapies, possibly due to its self-renewal and differentiation abilities. With the discovery of CSCs, researchers have been trying to explain whether OVs are well suited to eliminate CSCs. Two explanations for postulating OVs as ideal candidates for cancer therapy have been proposed: first, OVs are not subject to the same mechanisms responsible for chemotherapy and radiation resistance; second, viruses could be harnessed to express therapeutic transgenes that specifically target the features unique to CSCs or the properties CSCs rely on for self-renewal and differentiation. Indeed, initial studies suggest that OVs could effectively target CSCs in multiple tumor types. The focus of this review is to highlight recent studies related to the application of OVs on targeting CSCs, based on which, the challenges and perspectives for further research in this field will also be discussed. PMID- 27358870 TI - Quantitative analyses of myelofibrosis by determining hydroxyproline. AB - BACKGROUND: Myeloproliferative neoplasms (MPNs) are blood malignancies manifested in increased production of red blood cells, white blood cells, and/or platelets. Myelofibrosis is a subtype of MPNs characterized by the formation of scar-like tissues in the bone marrow due to abnormal hematopoiesis. It is considered a disease of both hematopoietic stem cells and stem cell niches. Patients with myelofibrosis have very poor prognosis, and there is no effective treatment so far. Myelofibrosis has routinely been detected by using histochemical staining methods which produce qualitative rather than quantitative results. In this study, we developed a quantitative assay of bone marrow myelofibrosis in JAK2V617F transgenic mice by determining hydroxyproline. METHODS: The JAK2V617F transgenic mice's tissue was collected to detect the bone marrow myelofibrosis. Statistical analyses were performed using the GraphPad Prism program. Differences of samples between two groups were accessed using t tests. P values less than 0.05 (2-tailed) were considered significantly different. RESULTS: We developed a quantitative method for detecting myelofibrosis by analyzing the content of hydroxyproline, a modified amino acid largely restricted to collagen which forms the fibrotic structure in bone marrow tissues. Our study also demonstrated age dependent development of bone marrow myelofibrosis in JAK2V617F transgenic mice. CONCLUSIONS: In the present study, we have developed a new method for detecting bone marrow myelofibrosis by analyzing hydroxyproline contents. The method is highly sensitive and accurate. It provides more accurate, representative, and quantitative information than histochemical analyses. We believe that this method should find wide applications for analyzing the progression of myelofibrosis and efficacy of drug treatment. PMID- 27358871 TI - Megakaryopoiesis and platelet production: insight into hematopoietic stem cell proliferation and differentiation. AB - Hematopoietic stem cells (HSCs) undergo successive lineage commitment steps to generate megakaryocytes (MKs) in a process referred to as megakaryopoiesis. MKs undergo a unique differentiation process involving endomitosis to eventually produce platelets. Many transcription factors participate in the regulation of this complex progress. Chemokines and other factors in the microenvironment where megakaryopoiesis and platelet production occur play vital roles in the regulation of HSC lineage commitment and MK maturation; among these factors, thrombopoietin (TPO) is the most important. Endomitosis is a vital process of MK maturation, and granules that are formed in MKs are important for platelet function. Proplatelets are firstly generated from mature MKs and then become platelets. The proplatelet production process was verified by novel studies that revealed that the mechanism is partially regulated by the invaginated membrane system (IMS), microtubules and Rho GTPases. The extracellular matrices (ECMs) and shear stress also affect and regulate the process while the mature MKs migrate from the marrow to the sub endothelium region near the venous sinusoids leading to the release of platelets into the circulation. This review describes the entire process of megakaryopoiesis in detail, illustrates both the transcriptional and microenvironmental regulation of MKs and provides insight into platelet biogenesis. PMID- 27358873 TI - Hemophagocytic lymphohistiocytosis: macrophages engulfing red cells and neutrophils. PMID- 27358872 TI - Clinical relevance between CALR mutation and myeloproliferative neoplasms. AB - In late 2013, somatic mutations in calreticulin (CALR), mainly those involving insertions and deletions in exon 9, attracted the great attention of hematologists and researchers. These JAK2- and MPL- mutual exclusive mutations enjoy a favorable specificity and prevalence (20-30%) in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF), suggesting promise for these mutations in disease management. Moreover, these genetic variations are now also considered as a group of independent risk factors for disease prognosis. In this mini-review, we will document the value of CALR mutations in disease diagnosis, prognosis, and therapeutic strategy selection, and we will discuss current advances in methods to detect these mutations. PMID- 27358875 TI - Shp2 regulates leukemic stem cell frequency in MLL-rearranged acute myeloid leukemia. PMID- 27358874 TI - Mesenchymal stem cells as delivery vectors for anti-tumor therapy. AB - Recent studies have demonstrated mesenchymal stem cells (MSCs) are able to migrate specifically to tumors and their metastatic sites when administered intravenously. This characteristic tumor tropism has opened up an emerging field to utilize MSCs as vectors to deliver anti-cancer agents for targeted therapies. Genetically engineered MSCs can specifically migrate to various tumors and locally secrete therapeutic proteins, such as interferon beta (IFN-beta) and IFN gamma, interleukin 12 and 24, tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or suicide gene/enzyme prodrug. In addition, MSCs have also been engineered to deliver oncolytic viruses and drug-loaded nanoparticles. Here, we present the characteristics of MSCs, the current progress on MSC mediated anti cancer agents delivery systems and the interaction between MSCs and tumors. PMID- 27358876 TI - Targeting of leukemia-initiating cells in acute promyelocytic leukemia. AB - Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) with peculiar molecular, phenotypic and clinical features and unique therapeutic response to specific treatments. The disease is characterized by a single, pathognomonic molecular event, consisting of the translocation t(15;17) which gives rise to the PML/retinoic acid receptor alpha (RARalpha) hybrid protein. The development of this leukemia is mainly related to the fusion oncoprotein PML/RARalpha, acting as an altered RAR mediating abnormal signalling and repression of myeloid differentiation, with consequent accumulation of undifferentiated promyelocytes. The prognosis of APL has dramatically been improved with the introduction in therapy of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). The main effect of these two drugs is linked to the targeting of either RAR moiety of the PML/RARalpha molecule and induction of cell differentiation (ATRA) or of the PML moiety of the fusion protein and induction of leukemic cell apoptosis, including leukemic progenitors (mostly induced by ATO). These two drugs exhibited excellent synergism and determine a very high rate of durable remissions in low/intermediate-risk APLs, when administered in the absence of any chemotherapeutic drug. The strong synergism and the marked clinical efficacy of these two agents when administered together seem to be related to their capacity to induce PML/RARalpha degradation and complete eradication of leukemia stem cells. PMID- 27358877 TI - Extensive cholelithiasis over 10 years in a patient with lymphoma. PMID- 27358878 TI - Mechanisms determining the fate of hematopoietic stem cells. AB - Successful in vitro expansion of hematopoietic stem cells (HSCs) will facilitate the application of HSC transplantation for the treatment of various diseases, including hematological malignancies. To achieve this expansion, the molecular mechanisms that control the fate of HSCs must be deciphered. Leukemia-initiating cells (LICs) or leukemia stem cells (LSCs) may originate from normal HSCs, which suggest that the dysregulation of the mechanisms that regulate the cell fate of HSCs may underlie leukemogenesis. Here we review the recent progress in the application of HSCs, the regulatory mechanisms of the fate of HSCs, and the origins of leukemia. PMID- 27358879 TI - Cancer stem cells and exosome signaling. AB - Exosomes have been recognized as mediators of intercellular communication among different cell populations in various biological model systems. By transfer of signaling molecules such as proteins, lipids, and RNAs between different cell types, exosomes are implicated in both physiological and pathological processes. The tumor microenvironment consists of multiple types of cells including adult stem cells, cancer stem cells, and stromal cells. These cells are known to intercommunicate with each other thereby modulating tumor progression. Recent studies have provided evidence demonstrating that exosomes mediate the interactions among different types of cells within the tumor microenvironment, providing new insight into how these cells interact with each other through exosome signaling. This review is focused on recent studies that have examined exosome-mediated intercommunication among cancer stem cells, adult stem cells, cancer cells, and stromal cells within the tumor microenvironment. Based on the current literature, it seems clear that adult stem cells and cancer stem cells secret exosomes that can be transferred to their surrounding cells thereby modulating cancer progression. Likewise, cancer cells and stromal cells also release exosomes that can be taken up by cancer stem cells or adult stem cells, leading to alterations to their phenotype. The molecular mechanisms and biological consequences of the exosome-mediated interactions of these cells remain to be further elucidated. A better understanding of how exosomes mediate intercellular communication in the tumor microenvironment and the specific biological consequences of these interactions will likely offer new opportunities in the development of diagnostic or therapeutic strategies against cancer. PMID- 27358880 TI - Interplay of retinal determination gene network with TGF-beta signaling pathway in epithelial-mesenchymal transition. AB - As a fundamental event in the generation of tissues and organs during embryogenesis, the epithelial-mesenchymal transition (EMT) has also been implicated in cancer progression by its ability to alter the plasticity of epithelial cells to acquire invasive properties. Evidence is mounting that ectopic activation of transforming growth factors beta (TGF-beta)/bone morphogenetic protein (BMP) superfamily members to enhance tumorigenesis and metastasis. In this respect, the Retinal Determination Gene Network (RDGN), which was identified to govern the normal initiation of the morphogenetic furrow in Drosophila, has now been found to be de-regulated in various types of cancers, and the key members of this network, DACH, SIX, and EYA, have emerged as novel co regulators of TGF- signaling during EMT. Understanding the molecular mechanism by which RDGN regulates TGF-beta/BMP signaling to influence EMT may lead to novel strategies for targeted therapies. PMID- 27358881 TI - Philadelphia chromosome-negative acute myeloid leukemia with 11q23/MLL translocation in a patient with chronic myelogenous leukemia. AB - Although defined by the presence of t(9;22), chronic myelogenous leukemia (CML) can have other concurrent additional cytogenetic changes, especially during disease progression. Additional chromosomal changes (ACAs) in CML often occur in Philadelphia chromosome (Ph)-positive cells and are associated with disease acceleration and treatment resistance. Occasionally chromosomal changes occur in Ph-negative cells and this phenomenon is often transient and does not correlate with disease progression. Very rarely myelodysplastic syndrome or acute leukemia can develop in Ph-negative cells. In this study, we report an unusual case of acute myeloid leukemia (AML) with 11q23/MLL translocation emerging from Ph negative cells in a patient with CML. PMID- 27358882 TI - Expression and function of P2 receptors in hematopoietic stem and progenitor cells. AB - Nucleotides have unambiguously emerged as a family of mediators of intercellular communication, which bind to a class of plasma membrane receptors, P2 receptors, to trigger intercellular signaling. P2 receptors can be further divided into P2X and P2Y subfamilies based on structure and function. Different hematopoietic cells express diverse spectrums of P2 receptors at different levels, including hematopoietic stem and progenitor cells (HSPCs). Extracellular adenosine triphosphate (ATP) exerts different effects on HSPCs, regulating cell proliferation, differentiation, migration, and chemotaxis, release of cytokines or lysosomal constituents, and generation of reactive oxygen or nitrogen species. The relationship between abnormal P2 receptor function and human diseases attracts more and more attention. This review summarizes the expression and function of P2 receptors in HSPCs and the relationship to hematopoietic diseases. PMID- 27358883 TI - Current insights into the diagnosis and treatment of inherited bone marrow failure syndromes in China. AB - Inherited bone marrow failure syndromes (IBMFs) account for 20% of pediatric BMFs. Although recommendations for the diagnosis and treatment of IBMFs in China have been published recently, improvements are still needed in making precise diagnoses and properly treating pediatric patients with IBMFs. This review provides current insights into IBMFs in China. The data of our single institution data showed that pediatric patients with IBMFs accounted for 7.4% of BMFs. However, the number of reported cases with IBMFs may be underestimated than the actual morbidity in China because of limitations in the detection approaches and lacking of awareness of these diseases in local hospitals. Although patients with IBMFs are candidates for bone marrow transplantation or gene therapy, their phenotypic heterogeneity can delay or incompetent diagnosis. The golden standard test for Fanconi anemia is the chromosome breakage test, but it can be completed by few hospital and diagnostic companies in China. In addition, there are still no consistent standardized testing methods for other rare IBMFs. Recently, the combined application of targeted capture and next-generation sequencing (NGS) provides and accurate and efficient diagnostic method for IBMFs. PMID- 27358884 TI - Calreticulin (CALR) mutation in myeloproliferative neoplasms (MPNs). AB - As a heterogeneous group of disease, myeloproliferative neoplasms (MPNs) have confused hematologists and hematopathologists with their protean clinical presentations and myriads of morphologies. A thought of classifying MPNs based on molecular alterations has gained popularity because there is increasing evidence that molecular or chromosomal alterations have a better correlation with clinical presentation, response to therapies, and prognosis than conventional morphological classification. This type of efforts has been facilitated by the advancement of molecular technologies. A significant number of gene mutations have been identified in MPNs with JAK2 and MPL being the major ones. However, a significant gap is present in that many cases of MPNs do not harbor any of these mutations. This gap is recently filled by the discovery of Calreticulin (CALR) mutation in MPNs without JAK2 or MPL mutation and since then, the clinical and molecular correlation in MPNs has become a hot research topic. There seems to be a fairly consistent correlation between CALR mutation and certain hematological parameters such as a high platelet count and a better prognosis in MPNs with CALR mutation. However, controversies are present regarding the risks of thrombosis, interactions of CALR with other gene mutation, the role of CALR in the pathogenesis, and the optimal treatment strategies. In addition, there are many questions remain to be answered, which all boiled down to the molecular mechanisms by which CALR causes or contributes to MPNs. Here, we summarized current published literatures on CALR mutations in MPNs with an emphasis on the clinical-molecular correlation. We also discussed the controversies and questions remain to be answered. PMID- 27358885 TI - Evaluation of TCR repertoire diversity in patients after hematopoietic stem cell transplantation. AB - T-cell receptor (TCR) repertoire analyses have been widely used to identify T cell populations of interest in cancer and autoimmunity and for characterizing immune repertoire reconstitution after hematopoietic stem cell transplantation (HSCT). Several decades of development and progress have led to the use of techniques for evaluating TCR repertoires in a more comprehensive, unbiased and fast manner, and the mechanisms of T cell immune reconstitution after HSCT and the new approaches used for recovering T cell repertoire diversity post HSCT have been more exhaustively documented to some degree. To better understand and characterize this progress, here we review recent studies on TCR repertoire diversity recovery in patients with leukemia and autoimmune disease who have received HSCT, impact factors and improvements in approaches for TCR repertoire recovery after HSCT. PMID- 27358886 TI - Current approaches and advance in mantle cell lymphoma treatment. AB - Mantle cell lymphoma (MCL) is a set of heterogeneous non-Hodgkin lymphoma characterized by involvement of lymph nodes, spleen, bone marrow and blood. Under conventional treatment, survival time is 4 to 5 years with short remission period and there is still no standard treatment for MCL. In general, a close observation period called "watchful waiting" is used in elderly patients with low-risk slow clinical progress. And intensive chemotherapy including high-dose of cytarabine +/- autologous hematopoietic stem cell transplantation (auto-HSCT) is recommended for younger and fit patients. Allogenic stem cell transplantation (allo-SCT) and drugs targeting the cell metabolic pathway, such as bortezomib (NF-kappaB inhibitor) and lenalidomide (anti-angiogenesis drug), are considerable treatments for relapsed/refractory patients. Clinical trials and less intensive chemotherapy such as R-CHOP (rituximab with cyclophosphamide, hydroxydaunomycin, oncovin and prednisone) and R-bendamustine should be considered for elderly MCL patients who are at intermediate/high risk. Recent clinical trials with ibrutinib (Bruton's Tyrosine Kinase inhibitor) and temsirolimus (mTOR inhibitor) have shown excellent efficacies in the treatment of MCL. This review will introduce the present status and major therapeutic progress in the treatment of MCL over recent years in order to provide a cutting edge to look into promising clinical progress of MCL. PMID- 27358889 TI - Study of peripheral stem cells mobilization as a treatment line of pediatric dilated cardiomyopathy. AB - BACKGROUND: Mobilizing hematopoietic stem cells may be a promising intervention for the treatment of idiopathic dilated cardiomyopathy (IDCM) in infant and children. So the aim of the work is to evaluate the efficacy of granulocyte colony stimulating factor (G-CSF) as a therapeutic modality in pediatric IDCM. METHODS: A randomized clinical trial was conducted on 40 pediatric patients with IDCM. They were subjected to history taking, clinical examination, serum lactate dehydrogenase (LDH), total creatinine phosphokinase (CPK), creatinine phosphokinase isoenzyme B (CK-MB) isoenzyme, and peripheral blood CD34(+) cell assessment before and at day 7 after subcutaneous G-CSF injection for 5 consecutive days. Echocardiography was done before and 1, 3 and 6 months after therapy. RESULTS: Clinical improvement in the form of regression of patients Modified Ross heart failure (MRHC) classification classes. Increased percentage of CD34(+) mobilized cells from the bone marrow, and significant increase in blood counts especially white blood cells 7 days after G-CSF injection. Significant improvement was found in echocardiographic data evaluating systolic function of the heart [Ejection fraction, Fractional shortening and systolic velocity at mitral annulus (Sm)]. CONCLUSIONS: Administration of G-CSF may be beneficial in improving systolic functions of the heart in pediatric IDCM and more studies with a large number of patients are needed. PMID- 27358890 TI - Genome editing and stem cell therapy pave the path for new treatment of sickle cell disease. AB - Sickle-cell disease (SCD), also known as sickle-cell anemia, is a hereditary blood disorder characterized by the presence of abnormal hemoglobin, the oxygen carrying protein found in red blood cells. This devastating hematologic disease affects millions of children worldwide. Currently the only available cure is an allogenic hematopoietic stem cell transplant (HSCT) which is limited by the scarcity of fully-matched donors. SCD is caused by a single nucleotide mutation in the beta-globin gene. Correction of this genetic defect would provide a cure for the disease. Two recent murine studies have provided proof of principle for such a strategy by correcting the mutation in hematopoietic stem cells (HSC) using genome editing techniques. With transformative advances being made in the genome editing field, effective and precise manipulation of cellular genomes is becoming highly feasible. Genome editing techniques in combination with stem cell therapy should provide a safe and curative treatment of various genetic diseases such as SCD. PMID- 27358887 TI - Alternative splicing acting as a bridge in evolution. AB - BACKGROUND: Alternative splicing (AS) regulates diverse cellular and developmental functions through alternative protein structures of different isoforms. Alternative exons dominate AS in vertebrates; however, very little is known about the extent and function of AS in lower eukaryotes. To understand the role of introns in gene evolution, we examined AS from a green algal and five fungal genomes using a novel EST-based gene-modeling algorithm (COMBEST). METHODS: AS from each genome was classified with COMBEST that maps EST sequences to genomes to build gene models. Various aspects of AS were analyzed through statistical methods. The interplay of intron 3n length, phase, coding property, and intron retention (RI) were examined with Chi-square testing. RESULTS: With 3 to 834 times EST coverage, we identified up to 73% of AS in intron-containing genes and found preponderance of RI among 11 types of AS. The number of exons, expression level, and maximum intron length correlated with number of AS per gene (NAG), and intron-rich genes suppressed AS. Genes with AS were more ancient, and AS was conserved among fungal genomes. Among stopless introns, non-retained introns (NRI) avoided, but major RI preferred 3n length. In contrast, stop containing introns showed uniform distribution among 3n, 3n+1, and 3n+2 lengths. We found a clue to the intron phase enigma: it was the coding function of introns involved in AS that dictates the intron phase bias. CONCLUSIONS: Majority of AS is non-functional, and the extent of AS is suppressed for intron-rich genes. RI through 3n length, stop codon, and phase bias bridges the transition from functionless to functional alternative isoforms. PMID- 27358888 TI - Haploidentical hematopoietic transplantation without T-cell depletion: current status and future perspectives. AB - Human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (HLA-haplo HSCT) without T-cell depletion has tremendously progressed over the past 20 years and has become a feasible treatment option for leukemia patients without an HLA-identical sibling donor. Advances in conditioning regimens, graft manipulation, and pharmacological graft-versus-host disease (GVHD) prophylaxis have reduced the risk of fatal graft failure and severe GVHD, two of the most serious complications of traversing the HLA barrier. According to clinical observations, killer immunoglobulin-like receptor (KIR) mismatch and donor-specific anti-HLA (DSA) antibodies-negative status play potential roles in reducing the risk of GVHD and graft failure following HLA haploidentical SCT. New strategies to improve transplant outcomes include donor lymphocyte, NK cell and selected T-cell subset infusion, mesenchymal stem cell (MSC) co-transplantation and interleukin-2 (IL-2) application. Future challenges remain in improving post-transplant immune reconstitution and finding the best approach to reduce the incidence and severity of GVHD while simultaneously preserving the graft-versus leukemia effect to prevent the recurrence of underlying malignancy. PMID- 27358891 TI - Let-7 regulates cardiomyocyte regeneration. PMID- 27358892 TI - Stem cells, environment, and cancer risk. PMID- 27358893 TI - Long non-coding RNA regulation of liver cancer stem cell self-renewal offers new therapeutic targeting opportunities. AB - Long non-coding RNAs (lncRNA) are critical regulators of gene expression, and can reprogram the transcriptome to modulate cellular processes involved in cellular growth and differentiation, and thereby contribute to tumorigenesis. In addition to effects on tumor cell growth, survival and cell signaling, lncRNA can modulate cancer stem cell (CSC) behavior, including the expression of pluripotency factors. The identification of lncRNA that are mechanistically linked to cancer stem cell self-renewal and differentiation, or aberrant signaling pathways associated with tumor growth or progression, offer new opportunities for therapeutic intervention. PMID- 27358894 TI - Adipose-derived stem cells from lean and obese humans show depot specific differences in their stem cell markers, exosome contents and senescence: role of protein kinase C delta (PKCdelta) in adipose stem cell niche. AB - BACKGROUND: Adipose-derived stem cells (ASC) and its exosomes are gaining utmost importance in the field of regenerative medicine. The ASCs tested for their potential in wound healing are predominantly derived from the subcutaneous depot of lean donors. However, it is important to characterize the ASC derived from different adipose depots as these depots have clinically distinct roles. METHODS: We characterized the ASC derived from subcutaneous and omental depots from a lean donor (sc-ASCn and om-ASCn) and compared it to the ASC derived from an obese donor (sc-ASCo and om-ASCo) using flow cytometry and real time qPCR. RESULTS: We show that stem cell markers Oct4, Sal4, Sox15, KLF4 and BMI1 have distinct expression patterns in each ASC. We evaluated the secretome of the ASC and characterized their secreted exosomes. We show long noncoding RNAs (lncRNAs) are secreted by ASC and their expression varied between the ASC's derived from different depots. Protein kinase C delta (PKCdelta) regulates the mitogenic signals in stem cells. We evaluated the effect of silencing PKCdelta in sc-ASCn, om-ASCn, sc-ASCo and om-ASCo. Using beta-galactosidase staining, we evaluated the percentage of senescent cells in sc-ASCn, om-ASCn, sc-ASCo and om-ASCo. Our results also indicated that silencing PKCdelta increases the percentage of senescent cells. CONCLUSIONS: Our case-specific study demonstrates a role of PKCdelta in maintaining the adipose stem cell niche and importantly demonstrates depot-specific differences in adipose stem cells and their exosome content. PMID- 27358895 TI - Myelodysplastic Syndrome with concomitant t(5;21)(q15;q22) and del(5)(q13q33): case report and review of literature. AB - Chromosomal abnormalities lead to the development of hematologic malignancies such as Myelodysplastic Syndrome (MDS). Known chromosomal changes causing MDS include deletion of the long arm of chromosome 5, runt-related transcription factor 1 (RUNX1) also known as acute myeloid leukemia 1 protein (AML1), and very rarely fusion genes involving RUNX1 at t(5;21)(q15;q22). We present a case of a 71-year-old female with MDS, refractory anemia with excess blasts, type 1, with a combination of two cytogenetic abnormalities, specifically a concomitant translocation between chromosomes 5q15 and 21q22 and deletion of chromosome 5q13q33. Fluorescence in-situ hybridization (FISH) using a probe for RUNX1 (AML1), localized to 21q22, showed three FISH signals for RUNX1, consistent with rearrangement of RUNX1. Therapy was started with Lenalidomide leading to normal blood counts. Most significantly, repeat cytogenetics revealed normal karyotype and resolution of deletion on the long arm of chromosome 5 and a t(5;21). FISH negative for deletion 5q. The results altogether meet criteria for a complete cytogenetic remission (CR). We report a new case of t(5;21)(q15;q22) involving the RUNX1 gene and del(5)(q13q33) in a MDS patient, a combination of chromosomal abnormalities heretofore not reported in the literature. RUNX1 rearrangement is usually associated with an adverse prognosis in AML and MDS. Deletions of 5q are typically associated with poor prognosis in AML, however it is usually associated with a favorable prognosis in MDS. Our patient responded very well to Lenalidomide therapy with achievement of CR. Lenalidomide is approved for treatment of anemia in low and intermediate risk MDS with del (5q), however based on a search of literature it seems that RUNX1 mutations are also more prominent in patients who have responded to Lenalidomide therapy. MDS is a genomically unstable disease. Hence, it is conceivable that our patient started with a 5q minus syndrome and then acquired the second hit RUNX1 translocation leading to an accelerated phase of myeloid neoplasm or refractory anemia with excess blasts, type 1. Hence, the temporal relationship between acquisition of del 5q and RUNX1 rearrangement may have influenced the clinical outcome and possibly response to therapy. PMID- 27358896 TI - Chromatin rules. PMID- 27358897 TI - Bone marrow fibrosis in primary myelofibrosis: pathogenic mechanisms and the role of TGF-beta. AB - Primary myelofibrosis (PMF) is a Philadelphia chromosome negative myeloproliferative neoplasm (MPN) with adverse prognosis and is associated with bone marrow fibrosis and extramedullary hematopoiesis. Even though the discovery of the Janus kinase 2 (JAK2), thrombopoietin receptor (MPL) and calreticulin (CALR) mutations have brought new insights into the complex pathogenesis of MPNs, the etiology of fibrosis is not well understood. Furthermore, since JAK2 inhibitors do not lead to reversal of fibrosis further understanding of the biology of fibrotic process is needed for future therapeutic discovery. Transforming growth factor beta (TGF-beta) is implicated as an important cytokine in pathogenesis of bone marrow fibrosis. Various mouse models have been developed and have established the role of TGF-beta in the pathogenesis of fibrosis. Understanding the molecular alterations that lead to TGF-beta mediated effects on bone marrow microenvironment can uncover newer therapeutic targets against myelofibrosis. Inhibition of the TGF-beta pathway in conjunction with other therapies might prove useful in the reversal of bone marrow fibrosis in PMF. PMID- 27358898 TI - Influence of IL-3 functional fragment on cord blood stem cell ex vivo expansion and differentiation. AB - BACKGROUND: Recombinant human interleukin-3 (rhIL-3) is a multiple hematopoietic growth factor, which enhances stem cell expansion and hematopoiesis regeneration in vitro and in vivo, when administrated in combination with other cytokines. However, the structure-function study of rhIL-3 remains rarely studied, so far. The purpose of this study was to recognize the short peptide with similar function as rhIL-3, and assess the hematopoietic efficacy in umbilical cord blood (UCB) stem cell culture as well. METHODS: Two novel monoclonal antibodies (mAb) (C1 and E1) were generated against rhIL-3 using hybridoma technique. Eleven short peptides were depicted and synthesized to overlap covering the full length sequence of rhIL-3. ELISA was employed to distinguish the antibody-binding peptide from the negative peptides. In addition, the multi-potential hematopoiesis capabilities of the positive peptides were evaluated by adding 25 ng/mL of each peptide to the culture medium of hematopoietic stem cells (HSCs) derived from UCB. Total nucleated cell number and the CD34(+) cell number from each individual treatment group were calculated on day 7. Correlated antibodies at 0.5 or 2 molar fold to each peptide were also tested in the stem cell expansion experiment, to further confirm the bioactivity of the peptides. RESULTS: Two peptides were recognized by the novel generated antibodies, using ELISA. Peptide 3 and 8 exhibited comparable hematopoiesis potentials, with 25.01+/-0.14 fold, and 19.89+/-0.12 fold increase of total nucleated cell number on day 7, respectively, compared with the basal medium control (4.93+/-0.55 fold). These biological effects were neutralized by adding the corresponding mAb at a dose dependent manner. CONCLUSIONS: Our results identified two specific regions of rhIL-3 responsible for HSC proliferation and differentiation, which were located from 28 to 49 amino acids (P3), and 107 to 127 amino acids (P8), respectively. The short peptide 3 and 8 might act synergistically, which could serve as an economic substitute to rhIL-3 in research laboratory. PMID- 27358899 TI - CD34(+) therapy-related acute promyelocytic leukemia in a patient previously treated for breast cancer. AB - Therapy-related acute myeloid leukemia (AML) is a long term complication of chemotherapy for a variety of cancers. In most cases, the marrow demonstrates high risk cytogenetics and the prognosis is poor. In a minority of patients "good risk" cytogenetics, including t(15;17)(q22;q12), are seen and the patient's prognosis is similar to those who have de novo disease. Currently we present a patient who developed therapy-related acute promyelocytic leukemia (APL) after chemoradiotherapy for breast cancer. This case was especially atypical because the leukemic cells were CD34(+), which is an unusual immunophenotype for APL. Recognition that this patient had APL, rather than the more common therapy related MDS or AML, was imperative to initiate chemotherapy in a timely manner. PMID- 27358900 TI - Acute promyelocytic leukemia co-existing with JAK2 V617F positive myeloproliferative neoplasm: a case report. AB - The V617F mutation of Janus-associated kinase 2 (JAK2) is commonly seen in myeloproliferative neoplasms (MPN). Transformation of JAK2 positive MPNs to acute leukemia has been reported. We here report a case of acute promyelocytic leukemia which was later confirmed to have a co-existing JAK2 V617F positive MPN. In addition, the patient was found to have FLT3-TKD mutation, which, together with PML/RARa, could play a role in the MPN transformation to APL. PMID- 27358901 TI - Primary splenic red pulp diffuse large B-cell lymphoma with anaplastic features. PMID- 27358902 TI - Identification of neural stem cell differentiation repressor complex Pnky-PTBP1. AB - Splicing increases immensely the complexity of gene products expressed in the cell. The precise regulation of splicing is critical for the development, homeostasis, and function of all tissues in the body, including those comprising the neural system. Ramos et al. recently identified Pnky as a long noncoding RNA expressed selectively in neural tissues that was implicated in the transition of neural stem cells (NSCs) to mature neurons. Pnky actions appeared to be mediated by its interaction with the splicing factor and RNA-binding protein (RBP) polypyrimidine tract-binding protein (PTBP1), as silencing either Pnky or PTBP1 modulated in similar ways the patterns of spliced and expressed mRNAs in the cell. Strikingly, lowering the expression levels of Pnky or PTBP1 in NSCs actually enhanced neurogenesis, suggesting that the Pnky-PTBP1 complex elicited a splicing program of suppression of neurogenesis. With rapid progress in the design and delivery of RNA-based therapies, interventions to reduce Pnky levels may prove beneficial towards enhancing neurogenesis in disease states characterized by aberrant neuronal loss. PMID- 27358903 TI - Analysis of TCR repertoires for tracking and evaluating distinct T cell subsets. PMID- 27358905 TI - The Demand for Cigarettes in Tanzania and Implications for Tobacco Taxation Policy. AB - The study attempts to estimate the demand for cigarettes in Tanzania and presents simulation results on the effect of the cigarette excise tax on smoking participation, government revenue, and related topics. After briefly summarizing the magnitude and spread of cigarette consumption in the country, the paper reviews some empirical estimates from African and other countries. The 2008 Tanzanian household budget survey was used to estimate the demand for cigarettes in Tanzania. The descriptive statistics suggest that the smoking prevalence for Tanzania is 15.35 percent with low variability across expenditure (income) groups. Smoking intensity and per capita consumption were estimated at 7.08 cigarettes and 1.33 cigarettes, respectively, a relatively low value. A two-part demand equation model was used to estimate various elasticities. For the overall equation, the price elasticities of smoking participation, smoking intensity, and total elasticity were estimated at -0.879, -0.853, and -1.732, respectively. Compared to similar results in other developing countries, the estimates appear quite high. When estimated by expenditure (income) groups, the magnitude of the elasticity appears higher among high expenditure groups than among low expenditure groups. Two simulation exercises were undertaken. First, the effect of different excise rates on smoking participation rate, cigarette consumption, tax revenue, and related responses was estimated and highlighted. Second, the same exercise was undertaken to determine the effect of a given increase in the cigarette excise tax on various expenditure groups. The overall results suggest that an increase in the excise tax on cigarettes in Tanzania would reduce cigarette consumption and increase government tax revenue. PMID- 27358906 TI - Data describing Rax positive optic-vesicle generation from mouse embryonic stem cells in vitro. AB - This article contains data related to the research article entitled "Specification of embryonic stem cell-derived tissues into eye fields by Wnt signaling using rostral diencephalic tissue-inducing culture" Sakakura (2016) [1]. Mouse embryonic stem cells (ESC) were used for the generation of optic vesicle-like tissues in vitro. In this article we described data in which a Rax::GFP knock-in ESC line was used to monitor the formation of optic tissues. In addition, we also described the data of regional marker expression of Rax, Sox2 and Pax6 in vivo around the forebrain and the eye tissues for comparative purposes. These data can be valuable to researchers interested in investigating forebrain and eye tissue development. PMID- 27358904 TI - HIV gp120 sequence variability associated with HAND in Hispanic Women. AB - OBJECTIVE: HIV-1 variants with different tropisms are associated with various neuropathologies. This study intends to determine if this correlation is determined by unique viral env sequences. We hypothesize that HIV-1 envelope gene sequence changes are associated with cognition status. METHODS: Viral RNA was extracted from peripheral blood mononuclear cells (PBMCs) co-cultures derived from HIV-1 infected Hispanic women that had been characterized for HIV associated neurocognitive disorders (HAND). RESULTS: Analyses of the C2V4 region of HIV gp120 demonstrated that increased sequence diversity correlates with cognition status as sequences derived from subjects with normal cognition exhibited less diversity than sequences derived from subjects with cognitive impairment. In addition, differences in V3 and V4 loop charges were also noted as well as differences in the N-glycosylation of the V4 region. CONCLUSIONS: Our data suggest that the genetic signature within the C2V4 region may contribute to the pathogenesis of HAND. HIV env sequence characteristics for the isolates grouped in milder forms of HAND can provide insightful information of prognostic value to assess neurocognitive status in HIV+ subjects, particularly during the era of highly prevalent milder forms of HAND. PMID- 27358907 TI - Mass spectrometry data from a quantitative analysis of protein expression in gills of immuno-challenged blue mussels (Mytilus edulis). AB - Here, we provide the dataset associated with our research article on the potential effects of ocean acidification on antimicrobial peptide (AMP) activity in the gills of Mytilus edulis, "Impact of ocean acidification on antimicrobial activity in gills of the blue mussel (Mytilus edulis)" [1]. Blue mussels were stimulated with lipopolysaccharides and samples were collected at different time points post injection. Protein extracts were prepared from the gills, digested using trypsin and a full in-depth proteome investigation was performed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Protein identification and quantification was performed using the MaxQuant 1.5.1.2 software, "MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification" [2]. PMID- 27358908 TI - Dataset of the use of tannin of nere (parkia-biglobosa) as a solution for the sustainability of the soil constructions in West Africa. AB - Soil is the main material of construction in African rural areas. Sustainability of construction with soil is a thorny problem to any builder. Finding ways to improve the durability of soil is not only essential but also salutary for the African rural community that mostly lives in soil-built houses that are very often short-lived. The present data assessed the resistance to simple compression and the resistance to bad weather by simulating rainfall alternations through a test of cycles of alternate watering and drying of blocks built from four types of different soils without binder, along with blocks built from the same soils. PMID- 27358909 TI - Data on respiratory variables in critically ill patients with acute respiratory failure placed on proportional assist ventilation with load adjustable gain factors (PAV+). AB - The data show respiratory variables in 108 critically ill patients with acute respiratory failure placed on proportional assist ventilation with load adjustable gain factors (PAV+) after at least 36 h on passive mechanical ventilation. PAV+ was continued for 48 h until the patients met pre-defined criteria either for switching to controlled modes or for breathing without ventilator assistance. Data during passive mechanical ventilation and during PAV+ are reported. Data are acquired from the whole population, as well as from patients with and without acute respiratory distress syndrome. The reported variables are tidal volume, driving pressure (DeltaP, the difference between static end-inspiratory plateau pressure and positive end-expiratory airway pressure), respiratory system compliance and resistance, and arterial blood gasses. The data are supplemental to our original research article, which described individual DeltaP in these patients and examined how it related to DeltaP when the same patients were ventilated with passive mechanical ventilation using the currently accepted lung-protective strategy "Driving pressure during assisted mechanical ventilation. Is it controlled by patient brain?" [1]. PMID- 27358910 TI - Data from quantitative label free proteomics analysis of rat spleen. AB - The dataset presented in this work has been obtained using a label-free quantitative proteomic analysis of rat spleen. A robust method for extraction of proteins from rat spleen tissue and LC-MS-MS analysis was developed using a urea and SDS-based buffer. Different fractionation methods were compared. A total of 3484 different proteins were identified from the pool of all experiments run in this study (a total of 2460 proteins with at least two peptides). A total of 1822 proteins were identified from nine non-fractionated pulse gels, 2288 proteins and 2864 proteins were identified by SDS-PAGE fractionation into three and five fractions respectively. The proteomics data are deposited in ProteomeXchange Consortium via PRIDE PXD003520, Progenesis and Maxquant output are presented in the supported information. The generated list of proteins under different regimes of fractionation allow assessing the nature of the identified proteins; variability in the quantitative analysis associated with the different sampling strategy and allow defining a proper number of replicates for future quantitative analysis. PMID- 27358911 TI - Proteome data of whole saliva which are associated with development of oral mucositis in head and neck cancer patients undergoing radiotherapy. AB - Saliva as major human body fluid may act as an indicator of oral disease status. Oral mucositis is a common and often treatment-limiting side effect of radiotherapy for head and neck cancer patients. In this dataset, we provide the complete proteome dataset (raw and search files) of the patients at baseline of radiotherapy treatment in patients undergoing radiotherapy analyzed by nano liquid chromatography coupled to mass spectrometry (LC-MS/MS). In the data set, 5323 tryptic peptides were identified which can be assigned to 487 distinct proteins (>=2 peptides). The MS data have been deposited to the ProteomeXchange ("ProteomeXchange provides globally coordinated proteomics data submission and dissemination" [1]) via the PRIDE partner repository with the dataset identifier PRIDE: PXD003230. The data are associated with the previously published work, "Differences in the whole saliva baseline proteome profile associated with development of oral mucositis in head and neck cancer patients undergoing radiotherapy" [2]. PMID- 27358912 TI - Renal rescue of dopamine D2 receptor function reverses renal injury and high blood pressure. AB - Dopamine D2 receptor (DRD2) deficiency increases renal inflammation and blood pressure in mice. We show here that long-term renal-selective silencing of Drd2 using siRNA increases renal expression of proinflammatory and profibrotic factors and blood pressure in mice. To determine the effects of renal-selective rescue of Drd2 expression in mice, the renal expression of DRD2 was first silenced using siRNA and 14 days later rescued by retrograde renal infusion of adeno-associated virus (AAV) vector with DRD2. Renal Drd2 siRNA treatment decreased the renal expression of DRD2 protein by 55%, and DRD2 AAV treatment increased the renal expression of DRD2 protein by 7.5- to 10-fold. Renal-selective DRD2 rescue reduced the expression of proinflammatory factors and kidney injury, preserved renal function, and normalized systolic and diastolic blood pressure. These results demonstrate that the deleterious effects of renal-selective Drd2 silencing on renal function and blood pressure were rescued by renal-selective overexpression of DRD2. Moreover, the deleterious effects of 45-minute bilateral ischemia/reperfusion on renal function and blood pressure in mice were ameliorated by a renal-selective increase in DRD2 expression by the retrograde ureteral infusion of DRD2 AAV immediately after the induction of ischemia/reperfusion injury. Thus, 14 days after ischemia/reperfusion injury, the renal expression of profibrotic factors, serum creatinine, and blood pressure were lower in mice infused with DRD2 AAV than in those infused with control AAV. These results indicate an important role of renal DRD2 in limiting renal injury and preserving normal renal function and blood pressure. PMID- 27358913 TI - Single-cell analysis of glandular T cell receptors in Sjogren's syndrome. AB - CD4+ T cells predominate in salivary gland (SG) inflammatory lesions in Sjogren's syndrome (SS). However, their antigen specificity, degree of clonal expansion, and relationship to clinical disease features remain unknown. We used multiplex reverse-transcriptase PCR to amplify paired T cell receptor alpha (TCRalpha) and beta transcripts of single CD4+CD45RA- T cells from SG and peripheral blood (PB) of 10 individuals with primary SS, 9 of whom shared the HLA DR3/DQ2 risk haplotype. TCRalpha and beta sequences were obtained from a median of 91 SG and 107 PB cells per subject. The degree of clonal expansion and frequency of cells expressing two productively rearranged alpha genes were increased in SG versus PB. Expanded clones from SG exhibited complementary-determining region 3 (CDR3) sequence similarity both within and among subjects, suggesting antigenic selection and shared antigen recognition. CDR3 similarities were shared among expanded clones from individuals discordant for canonical Ro and La autoantibodies, suggesting recognition of alternative SG antigen(s). The extent of SG clonal expansion correlated with reduced saliva production and increased SG fibrosis, linking expanded SG T cells with glandular dysfunction. Knowledge of paired TCRalpha and beta sequences enables further work toward identification of target antigens and development of novel therapies. PMID- 27358916 TI - Structural characterization of PEGylated polyethylenimine-entrapped gold nanoparticles: an NMR study. AB - NMR spectroscopy has been proven to be a useful method to characterize the spatial structure of polymer-protected nanoparticles (NPs). In the present study, polyethylenimine (PEI) partially modified with polyethylene glycol (PEG) was used as a template to form gold NPs (Au NPs) via either sodium borohydride reduction or PEI amine-mediated self-reduction of Au salt. The formed two types of PEGylated PEI-entrapped Au NPs (PEI-mPEG-Au NPs) were characterized by UV-vis spectroscopy and transmission electron microscopy, and their internal structures were characterized using NMR techniques. We show that the formed PEI-mPEG-Au NPs display a significant downfield shift in the proton signals of the innermost PEI methylene rather than the outer PEG methylene when compared to that of PEI-mPEG without Au NP entrapment. This result indicates that a strong interaction exists between the Au NPs and the innermost PEI, suggesting that the Au NPs are entrapped within individual PEI-mPEG instead of being stabilized by the surface PEG chains. In addition, the NMR diffusion coefficients of PEI (or PEG) in the PEI-mPEG-Au NPs are much higher than that of PEI-mPEG (without Au NPs), further demonstrating the effective Au NP entrapment. The present study provides a new physical insight into the internal spatial structure of polymer-protected Au NPs disclosed by NMR techniques, which may be used for structural characterization of other NP/polymer nanocomposites. PMID- 27358914 TI - Attenuation of lung fibrosis in mice with a clinically relevant inhibitor of glutathione-S-transferase pi. AB - Idiopathic pulmonary fibrosis (IPF) is a debilitating lung disease characterized by excessive collagen production and fibrogenesis. Apoptosis in lung epithelial cells is critical in IPF pathogenesis, as heightened loss of these cells promotes fibroblast activation and remodeling. Changes in glutathione redox status have been reported in IPF patients. S-glutathionylation, the conjugation of glutathione to reactive cysteines, is catalyzed in part by glutathione-S transferase pi (GSTP). To date, no published information exists linking GSTP and IPF to our knowledge. We hypothesized that GSTP mediates lung fibrogenesis in part through FAS S-glutathionylation, a critical event in epithelial cell apoptosis. Our results demonstrate that GSTP immunoreactivity is increased in the lungs of IPF patients, notably within type II epithelial cells. The FAS-GSTP interaction was also increased in IPF lungs. Bleomycin- and AdTGFbeta-induced increases in collagen content, alpha-SMA, FAS S-glutathionylation, and total protein S-glutathionylation were strongly attenuated in Gstp-/- mice. Oropharyngeal administration of the GSTP inhibitor, TLK117, at a time when fibrosis was already apparent, attenuated bleomycin- and AdTGFbeta-induced remodeling, alpha-SMA, caspase activation, FAS S-glutathionylation, and total protein S-glutathionylation. GSTP is an important driver of protein S glutathionylation and lung fibrosis, and GSTP inhibition via the airways may be a novel therapeutic strategy for the treatment of IPF. PMID- 27358915 TI - STAT3 accelerates uterine epithelial regeneration in a mouse model of decellularized uterine matrix transplantation. AB - Although a close connection between uterine regeneration and successful pregnancy in both humans and mice has been consistently observed, its molecular basis remains unclear. We here established a mouse model of decellularized uterine matrix (DUM) transplantation. Resected mouse uteri were processed with SDS to make DUMs without any intact cells. DUMs were transplanted into the mouse uteri with artificially induced defects, and all the uterine layers were recovered at the DUM transplantation sites within a month. In the regenerated uteri, normal hormone responsiveness in early pregnancy was observed, suggesting the regeneration of functional uteri. Uterine epithelial cells rapidly migrated and formed a normal uterine epithelial layer within a week, indicating a robust epithelial-regenerating capacity. Stromal and myometrial regeneration occurred following epithelial regeneration. In ovariectomized mice, uterine regeneration of the DUM transplantation was similarly observed, suggesting that ovarian hormones are not essential for this regeneration process. Importantly, the regenerating epithelium around the DUM demonstrated heightened STAT3 phosphorylation and cell proliferation, which was suppressed in uteri of Stat3 conditional knockout mice. These data suggest a key role of STAT3 in the initial step of the uterine regeneration process. The DUM transplantation model is a powerful tool for uterine regeneration research. PMID- 27358917 TI - An electrochemical biosensor for rapid detection of E. coli O157:H7 with highly efficient bi-functional glucose oxidase-polydopamine nanocomposites and Prussian blue modified screen-printed interdigitated electrodes. AB - The presence of pathogenic bacteria in foods has always been a great threat to the wellbeing of people and the revenue of food manufacturers. Therefore, the demand for advanced detection methods that can sensitively and rapidly detect these pathogens has been of great importance. This study reports an electrochemical biosensor for rapid detection of E. coli O157:H7 with the integration of bifunctional glucose oxidase (GOx)-polydopamine (PDA) based polymeric nanocomposites (PMNCs) and Prussian blue (PB) modified screen-printed interdigitated microelectrodes (SP-IDMEs). The core-shell magnetic beads (MBs) GOx@PDA PMNCs were first synthesized by the self-polymerization of dopamine (DA). Gold nanoparticles (AuNPs) were dispersed on the surface of PMNCs through biochemical synthesis to achieve further highly efficient adsorption of antibodies (ABs) and GOx. The final product ABs/GOxext/AuNPs/MBs-GOx@PDA PMNCs served as the carrier to separate target bacteria from food matrices as well as the amplifier for electrochemical measurement. The unbound PMNCs were separated by a filtration step and transferred into glucose solution to allow the enzymatic reaction to occur. The change of the current response was measured with an electrochemical detector using PB-modified SP-IDMEs. The constructed biosensor has been proven to be able to detect E. coli O157:H7 with the detection limit of 10(2) cfu ml(-1). The bifunctional PMNCs contain a high load of enzyme and can optimally utilize the binding sites on bacterial cells, which efficiently amplify the signals for measurement. The biosensor in this study exhibited good specificity, reproducibility, and stability and is expected to have a great impact on applications in the detection of foodborne pathogens. PMID- 27358918 TI - [Wise and slowly]. PMID- 27358919 TI - [Toxic epidermal necrolysis]. PMID- 27358920 TI - [Lyell's syndrome]. PMID- 27358921 TI - [Not Available]. PMID- 27358922 TI - [Not Available]. PMID- 27358923 TI - [Not Available]. PMID- 27358924 TI - [Not Available]. PMID- 27358925 TI - [Not Available]. PMID- 27358926 TI - [Not Available]. PMID- 27358927 TI - ECDC public consultation on the use of neuraminidase inhibitors. PMID- 27358928 TI - First European Union Laboratory Capability Monitoring System report published. PMID- 27358929 TI - [The editors of the journal "Vestnik obshchestvennoy gigieny, sudebnoy, and prakticheskoy meditsiny (The Bulletin of Public Hygiene, Forensic, and Practical Medicine) "V.I. Grebenshchikov and M.S. Uvarov]. PMID- 27358930 TI - [The foreign experience with the application of the modern radiodiagnostic methods for the estimation of prescription of death coming and time of infliction of injury]. AB - We undertook the analysis of the foreign publications concerning the application of the modern radiodiagnostic methods (including MSCT- and MRI-visualization) with reference to the solution of the traditional problems facing forensic medical expertise, such as the estimation of prescription of death coming and time of infliction of injury in the dead bodies. Both advantages and disadvantages of postmortem visualization of the corpses of adult subjects are discussed taking into consideration the period of time that elapsed between the death and the onset of the study as well as the character of the injuries. It was shown that the examination of the corpses using the up-to-date methods of radiodiagnostics prior to autopsy makes it possible for morphologists, jointly with radiologists, to identify, to see in the new light, and to evaluate the number of charges in the dead body, such as the alteration of the blood cell sedimentation rate, the formation of postmortem hypostases in the internal organs, the hardening of the walls of aorta and major blood vessels, right heart dilatation, gradual smoothing of the borderline between grey and white matter of the brain. Virtual autopsy can be useful , even for the study of such long-term processes in the corpses as putrefaction, saponification, mummification, and peat tanning. Moreover, this technique may be instrumental in the elucidation of the specific features of topographic-anatomical relationships between individual 'tissues and organs, detection of the concealed lesions, and a variety of pathological changes. Postmortem visualization allows for the quantitative evaluation of the severity of these transformations and the preliminary estimation of prescription of death coming. Also, radiodiagnostic methods can be employed to reliably visualize and measure various hemorrhagic events (from the density of such ones as liquid and clotted blood) in the tissues surrounding the fractures, in body cavities, and internal organs as well as to establish the facts of inter-vital aspiration of blood, alimentary masses, liquid and solid foreign bodies penetrating into the upper sections of the respiratory and gastrointestinal tracts as the consequence f an injury. It is concluded that the postmortem visualization techniques employed to estimate prescription of death coming and time of infliction of injury as well as other complicated problems facing forensic medical expertize need the further scientifically based development. PMID- 27358931 TI - [The current state-of-the-art of the expert evaluation of medical documentation pertaining to the cases of death from an injury inflicted in a healthcare facility in the late; post-traumatic period]. AB - This article presents a concise review of the literature data concerning the modern methods for the expert evaluation of medical documentation as an object of forensic medical examination. The authors lay special emphasis on the practical significance of this issue for the scientifically sound substantiation of the results of forensic medical expertise carried out for the elucidation of the causes of death and the relationship between the injury and the outcome of the medical aid provided for its treatment. The expert evaluation of medical documentation is equally important for the assessment of the harm to health and the cause of death as a consequence of a thermal and/or mechanical injury inflicted during the hospital stay and in the late post-traumatic period. PMID- 27358932 TI - [Forensic medical diagnostics of intra-vitality of the strangulation mark by morphological methods]. AB - The objective of the present study WaS to overview the current domestic and foreign literature concerning the up-to-date methods employed for the expert evaluation of intra-vitality of the strangulation mark. The secondary objective was to propose the new approaches for addressing this problem. The methods of expert diagnostics with a view to determining the time of infliction of injuries as exemplified by mechanical asphyxia are discussed. It is concluded that immunohistochemical and morphometric studies provide the most promising tools for the evaluation of intra-vitality of the strangulation mark for the purpose of forensic medical expertise. PMID- 27358933 TI - [The 10th scientific and practical conference of young scientists and specialists of the Moscow Society of Forensic Medical Experts "Forensic medical science and practice", Moscow, 20 October 2015]. PMID- 27358935 TI - California State Hospital Violence Assessment and Treatment (Cal-VAT) guideline. AB - Here we provide comprehensive guidelines for the assessment and treatment of violence and aggression of various etiologies, including psychotic aggression and impulsive aggression due to schizophrenia, mood disorders, ADHD, or trauma, and predatory aggression due to psychopathy and other personality disorders. These guidelines have been developed from a collection of prescribing recommendations, clinical trial results, and years of clinical experience in treating patients who are persistently violent or aggressive in the California Department of State Hospital System. Many of the recommendations provided in these guidelines employ off-label prescribing practices; thus, sound clinical judgment based on individual patient needs and according to institution formularies must be considered when applying these guidelines in clinical practice. PMID- 27358936 TI - Clinical assessment of psychotic and mood disorder symptoms for risk of future violence. AB - This article reviews important components to consider when evaluating the relationship of psychotic and mood disorder symptoms to violence. Particular attention is given to assessing persecutory delusions and command auditory hallucinations. Clinical implications of research findings to evaluating violence risk in psychiatric patients are reviewed. PMID- 27358934 TI - Impact of uncertainty in longitudinal T1 measurements on quantification of dynamic contrast-enhanced MRI. AB - The objective of this study was to assess the uncertainty in T1 measurement, by estimating the repeatability coefficient (RC) from two repeated scans, in normal appearing brain tissues employing two different T1 mapping methods. All brain MRI scans were performed on a 3 T MR scanner in 10 patients who had low grade/benign tumors and partial brain radiation therapy (RT) without chemotherapy, at pre-RT, 3 weeks into RT, end RT (6 weeks) and 11, 33, and 85 weeks after RT. T1-weighted images were acquired using (1) a spoiled gradient echo sequence with two flip angles (2FA: 5 degrees and 15 degrees ) and (2) a progressive saturation recovery sequence (pSR) with five different TR values (100-2000 ms). Manually drawn volumes of interest (VOIs) included left and right normal putamen and thalamus in gray matter, and frontal and parietal white matter, which were distant from tumors and received a total of accumulated radiation doses less than 5 Gy at 3 weeks. No significant changes or even trends in mean T1 from pre-RT to 3 weeks into RT in these VOIs (p >= 0.11, Wilcoxon sign test) allowed us to calculate the repeatability statistics of between-subject means of squares, within-subject means of squares, F-score, and RC. The 2FA method produced RCs in the range of (9.7-11.7)% in gray matter and (12.2-14.5)% in white matter; while the pSR method led to RCs ranging from 10.9 to 17.9% in gray matter and 7.5 to 10.3% in white matter. The overall mean (+/-SD) RCs produced by the two methods, 12.0 (+/-1.6)% for 2FA and 12.0 (+/-3.8)% for pSR, were not significantly different (p = 0.97). A similar repeatability in T1 measurement produced by the time efficient 2FA method compared with the time consuming pSR method demonstrates that the 2FA method is desirable to integrate into dynamic contrast enhanced MRI for rapid acquisition. PMID- 27358937 TI - Clinical assessment of psychotic and mood disorder symptoms for risk of future violence. PMID- 27358938 TI - The importance of Developmental Origins of Health and Disease research for Africa. PMID- 27358940 TI - Bilateral leg weakness and hypesthesia in a middle-aged female: question. PMID- 27358939 TI - [Diagnosis and treatment of Zika virus disease (first edition in 2016)]. PMID- 27358941 TI - Progressive headache and lethargy in a middle-age female patient: question. PMID- 27358942 TI - Radioactive Standards Laboratory ININ as a reference laboratory in Mexico. AB - The Radioactive Standards Laboratory of the National Institute of Nuclear Research is the National reference laboratory for the measurement of radioactivity in Mexico. It has a gamma-ray spectrometry system with a high purity Ge-detector for measurements from 50 keV to 2000 keV, and develops standardized radioactive (beta-particle and gamma-ray emitting) sources in different geometries with uncertainties less than or equal to 5% for applications such as the calibration of radionuclide calibrators (clinically used dose calibrators), Ge-detectors and NaI(Tl) detectors. PMID- 27358943 TI - Comparison exercise on activity determination of radioactive waste drums in Taiwan. AB - The National Radiation Standard Laboratory of Taiwan organized in 2014 a comparison exercise by distributing 210 L drum-typed samples to seven radioactive waste analysis laboratories in Taiwan. Four drums were filled with uniformly distributed active carbon, water, resin and concrete, respectively and five drums were filled with cracked metals and heterogeneously distributed radioactive sources. Measurement uncertainties of participants results are in the range 3-40% (k=2) and about 96% of the reported results produced En values (ISO, 1997) smaller than one for drums with activity uniformly distributed. The minimum discrepancies, expressed as Bi values (ISO, 1997), of drums with heterogeneously distributed 137Cs and 60Co were 0.34 and 0.17, respectively. PMID- 27358944 TI - Monte Carlo based approach to the LS-NaI 4pibeta-gamma anticoincidence extrapolation and uncertainty. AB - The 4pibeta-gamma anticoincidence method is used for the primary standardization of beta-, beta+, electron capture (EC), alpha, and mixed-mode radionuclides. Efficiency extrapolation using one or more gamma ray coincidence gates is typically carried out by a low-order polynomial fit. The approach presented here is to use a Geant4-based Monte Carlo simulation of the detector system to analyze the efficiency extrapolation. New code was developed to account for detector resolution, direct gamma ray interaction with the PMT, and implementation of experimental beta-decay shape factors. The simulation was tuned to 57Co and 60Co data, then tested with 99mTc data, and used in measurements of 18F, 129I, and 124I. The analysis method described here offers a more realistic activity value and uncertainty than those indicated from a least-squares fit alone. PMID- 27358945 TI - Dry deposition velocity of 137Cs and 134Cs in Spain after the Fukushima Dai-Ichi Nuclear Power Plant accident. AB - Aerosol samples collected at the Technical University of Catalonia in Barcelona were analysed for traces of 134Cs and 137Cs emitted during the Fukushima Dai-ichi Nuclear Power Plant accident in March 2011. Samples were collected with a high volume airborne particulate sampling system, and with a dry and wet deposition collection system for subsequent analysis. Due to the very low activities, the filters were measured in an underground ultra-low background laboratory. This has enabled the characterization of dry velocity deposition for 134Cs and 137Cs. Results show a dry velocity deposition of 0.07 cm s-1. PMID- 27358946 TI - Determination of 210Pb, 210Po, 226Ra, 228Ra and uranium isotopes in drinking water in order to comply with the requirements of the EU 'Drinking Water Directive. AB - The European Union published in 2013 a new Drinking Water Directive with stricter requirements for measuring natural radioactivity. In order to adhere to this, a method for sequential separation of 210Pb, 210Po, 238U and 234U in drinking water was applied using UTEVA(r) and Sr resins. Polonium-210, 238U and 234U were quantified using alpha-particle spectrometry and 210Pb using liquid scintillation counting. Radium-226 and 228Ra were determined using 3M Empore Radium RAD Disks, and their quantification was done using a QuantulusTM 1220 liquid scintillation counter. PMID- 27358947 TI - Design of cosmic veto shielding for HPGe-detector spectrometer. AB - A Monte Carlo simulation to optimize the shielding design of a cosmic-veto HPGe spectrometer is described. The incident sources were simulated using the CRY code and the effect on the integral background count rate of different shielding structures was evaluated using the simulation code GEANT4 with application of veto mechanics during simulation. This procedure has been validated by experimental results, and another optimized cosmic veto shielding for an HPGe detector has been illustrated. PMID- 27358948 TI - Application of GUM Supplement 1 to uncertainty of Monte Carlo computed efficiency in gamma-ray spectrometry. AB - The uncertainty of quantities relevant in gamma-ray spectrometry (efficiency, transfer factor, self-attenuation FA and coincidence summing FC correction factors) is realistically evaluated by Monte Carlo propagation of the distributions characterizing the parameters on which these quantities depend. Probability density functions are constructed and summarized as recommended in the GUM Supplement 1 and compared with the values obtained using the traditional approach (GUM uncertainty framework). Special cases when this approach encounters difficulties (FC uncertainty due to the uncertainty of decay scheme parameters, effect of activity and matrix inhomogeneity on efficiency) are also discussed. PMID- 27358949 TI - MGMA takes positions on 2015 Medicare physician fee schedule proposals. PMID- 27358950 TI - Partnerships for prevention. PMID- 27358952 TI - What are you wearing?. PMID- 27358951 TI - When it comes to payments, closely review your options. PMID- 27358953 TI - Preserving patient safety. PMID- 27358954 TI - New Zealand Guidelines for Adult Echocardiography 2015: The Cardiac Society of Australia and New Zealand. PMID- 27358955 TI - Response. PMID- 27358956 TI - Response. PMID- 27358957 TI - Response. PMID- 27358958 TI - Response. PMID- 27358959 TI - Response. PMID- 27358960 TI - Response. PMID- 27358961 TI - Response. PMID- 27358962 TI - Editorial. PMID- 27358963 TI - Response. PMID- 27358964 TI - Response. PMID- 27358965 TI - Response. PMID- 27358966 TI - Response. PMID- 27358967 TI - Response. PMID- 27358968 TI - Response. PMID- 27358969 TI - In Memoriam: Sandy Ford (1950-2015). PMID- 27358970 TI - From Farm to Fable. PMID- 27358971 TI - Tuberculosis and the traveller: evaluating and reducing risk through travel consultation. AB - BACKGROUND: Although the last 10 years have seen a slow decline in global tuberculosis (TB) incidence, it remains one of the most significant infectious diseases worldwide, with an estimated 9.6 million new cases and 1.5 million deaths in 2014. The consequences of contracting TB can be significant for the individual, with extended treatment requirements, risk of long-term health consequences and the possibility of transmitting infection to others among the complications of disease. METHODS: This review article discusses the risk of TB infection as a result of international travel including evaluation of risk, risk reduction and a proposed testing strategy for travel-related TB infection. A review of the relevant literature combined with expert opinion was used to formulate this article. RESULTS: The global TB epidemic is varied and dynamic, including changing patterns of both drug sensitive and drug resistant disease. The annual incidence of TB in individual countries such as South Africa may be greater than 800/100,000, while multidrug resistance is found in up to 19% of new cases in the Russian Federation. Recent surveys of traveller risk are presented for short and long-term travellers to various countries and settings. Overall, risk to travelers is low, with rates of acquiring latent TB less than 1% per travel year for most settings. However, detailed travel evaluation is necessary to evaluate individual risk. Travellers with immunosuppressive conditions are at high risk for progression to active disease if infected, and should have special consideration in travel consultation. DISCUSSION: It is important for practitioners giving advice regarding tuberculosis risk and travel to access up to-date information regarding local conditions. This article provides an approach to assessment and management of TB in travellers, including a guide to pre- and post-travel evaluation, testing and vaccination. PMID- 27358972 TI - Exportations of Symptomatic Cases of MERS-CoV Infection to Countries outside the Middle East. AB - In 2012, an outbreak of infection with Middle East respiratory syndrome coronavirus (MERS-CoV), was detected in the Arabian Peninsula. Modeling can produce estimates of the expected annual number of symptomatic cases of MERS-CoV infection exported and the likelihood of exportation from source countries in the Middle East to countries outside the region. PMID- 27358973 TI - [Chronic pancreatitis diagnosed after the first attack of acute pancreatitis]. PMID- 27358975 TI - [Corticosteroids in the treatment of infectious diseases]. PMID- 27358974 TI - RESPONSE. PMID- 27358976 TI - [Fecal microbiota transplantation]. PMID- 27358978 TI - [Not Available]. PMID- 27358977 TI - [Lead poisoning]. PMID- 27358980 TI - [Metformin in patients with type 2 diabetes mellitus and lactic acidosis]. PMID- 27358979 TI - [Epicardial fat as another stone in the mosaic of cardiovascular risk specification?]. PMID- 27358981 TI - [The population of patients with diabetes has changed, the patients live longer and are at greater risk of heart failure]. PMID- 27358982 TI - [DRESS syndrome]. PMID- 27358983 TI - Malaria. PMID- 27358984 TI - John Keats: science and sympathy. PMID- 27358985 TI - Robert Charles Strunk. PMID- 27358986 TI - Author Response. PMID- 27358987 TI - Author Response. PMID- 27358988 TI - Caring for memories. PMID- 27358989 TI - Anne Deborah Atai-Omoruto. PMID- 27358990 TI - Glamour. PMID- 27358991 TI - Desperately seeking reductions in health inequalities: perspectives of UK researchers on past, present and future directions in health inequalities research. AB - Following government commitments to reducing health inequalities from 1997 onwards, the UK has been recognised as a global leader in health inequalities research and policy. Yet health inequalities have continued to widen by most measures, prompting calls for new research agendas and advocacy to facilitate greater public support for the upstream policies that evidence suggests are required. However, there is currently no agreement as to what new research might involve or precisely what public health egalitarians ought to be advocating. This article presents an analysis of discussions among 52 researchers to consider the feasibility that research-informed advocacy around particular solutions to health inequalities may emerge in the UK. The data indicate there is a consensus that more should be been done to learn from post-1997 efforts to reduce health inequalities, and an obvious desire to provide clearer policy guidance in future.However, discussions as to where researchers should now focus their efforts and with whom researchers ought to be engaging reveal three distinct ways of approaching health inequalities, each of which has its own epistemological foundations. Such differences imply that a consensus on reducing health inequalities is unlikely to materialise. Instead, progress seems most likely if all three approaches are simultaneously enabled. PMID- 27358992 TI - [Domestication of suspension CHO cells and its application in the expression of anti-PSMA antibody]. AB - OBJECTIVE: To domesticate adherent Chinese hamster ovary (CHO) cells into suspension CHO cells (CHO-S) cultured in serum-free medium,and evaluate the application of the CHO-S cells in antibody expression. METHODS: Adherent CHO cells were domesticated into CHO-S cells through suspension culture and gradually decreasing the serum concentration, and eventually the cells were cultured in serum-free medium. Based on the anti-prostate-specific membrane antigen ( PSMA) single chain antibody fragment ( Sc Fv) gene sequence obtained from a phage display library, the genes of heavy and light chains were designed, synthesized and cloned into the pc DNA3. 1 vector,and the products were named pc DNA3. 1-HC and pc DNA3. 1-LC respectively. The plasmids were transiently transfected at the ratio of light and heavy chain 3 ? 1 into CHO-S cells using Free Style MAX transfection reagent, and the supernatants were harvested at day 7 after transfection. SDS-PAGE and Western blotting were used to detect the antibody expression,and flow cytometry was applied to evaluate its binding activity to PSMA positive cells. RESULTS: The adherent CHO cells were successfully domesticated into CHO-S cells. Expression plasmids for anti-PSMA antibody heavy chain and light chain were successfully constructed,and anti-PSMA antibody could be secretively expressed in CHO-S cells. Flow cytometry showed that the expressed antibody could specifically bind to PSMA positive cells. CONCLUSION: CHO-S cel s were successful y domesticated from adherent CHO cells, and could be used for antibody expression. This study provided a useful tool for further antibody expression, purification and function study. PMID- 27358993 TI - Response to Hall. PMID- 27358994 TI - Moving Forward. PMID- 27358995 TI - Relationships between water quality parameters in rivers and lakes: BOD5, COD, NBOPs, and TOC. AB - Biological oxygen demand (BOD5) or chemical oxygen demand (COD) analysis is widely used to evaluate organic pollutants in water systems as well as the efficiency of wastewater treatment plants. However, both analysis methods have restrictions such as being insensitive, imprecise, time-consuming, and the production of chemical waste. Therefore, total organic carbon (TOC) analysis for organic pollutants has been considered for an alternative analysis instead of BOD5 or COD. Several studies have investigated the replacement of BOD5 or COD with TOC in wastewater samples; however, few studies have investigated the relationships between water quality parameters in rivers and lakes. Therefore, this study evaluated the relationships between BOD5, COD, or NBOPs and TOC by the analysis of national water quality monitoring data of rivers and lakes for 5 years. High correlation coefficients (r) of 0.87 and 0.66 between BOD5 and TOC (p < 0.05) were obtained for rivers and lakes, respectively, and strong correlation coefficients (r) of 0.93 and 0.75 were observed between COD and TOC (p < 0.05) for rivers and lakes, respectively. The correlation coefficient (r) between NBOPs and TOC was 0.93 for rivers and 0.72 for lakes. The coefficients of determination (R 2) were 0.75 and 0.44 between BOD5 and TOC for rivers and lakes as well as were 0.87 and 0.57 between COD and TOC for rivers and lakes, respectively. The coefficient of determination (R 2) between NBOPs and TOC was 0.73 for rivers and 0.52 for lakes. PMID- 27358996 TI - Monitoring and assessment of anthropogenic activities in mountain lakes: a case of the Fifth Triglav Lake in the Julian Alps. AB - The Fifth Triglav Lake is a remote mountain lake in the Julian Alps. The area of the Julian Alps where the lake is situated is protected by law and lies within the Triglav National Park. Mountain lakes in Slovenia were considered for a long time as pristine, unpolluted lakes, but analyses in the last decade revealed considerable human impact even in such remote places. Eutrophication or excessive accumulation of nutrients is the main problem of most lakes in the temperate climatic zone, also in Slovenia. Since the introduction of fish in 1991, the lake is going through a series of changes for which we do not know exactly where they lead, so the monitoring and assessment of anthropogenic activities are of great importance. For this purpose, a qualitative multiattribute decision model was developed with DEX method to assess ecological effects on the lake. The extent of the ecological effects on the lake is assessed using four main parameters: the trophic state, lake characteristics, environmental parameters, and anthropogenic stressors. Dependence of environmental impact on various external factors beyond human control, such as temperature, precipitation, retention time, and factors on which we have influence, such as the amount of wastewater and the presence of fish in the lake, were also evaluated. The following data were measured: chlorophyll a, nutrients, TP, oxygen, C/N ratio, nutrients in sediment, temperature, precipitation, retention time, and volume. We made assumptions about fish and wastewater, which we could not measure. The main contributions of this work are the designed model and the obtained findings for the Fifth Triglav Lake that can help not only scientists in understanding the complexity of lake watershed systems and interactions among system components but also local authorities to manage and monitor the lake aquatic environment in an effective and efficient way. The model is flexible and can be also used for other lakes, assuming that the used parameters are measured and anthropogenic stressors are adjusted to a specific situation. The results of assessment are of particular interest for decision makers in protected areas, providing a new approach to the management of the quality of the water environment. PMID- 27358997 TI - Rapid integrated water quality evaluation of Mahisagar river using benthic macroinvertebrates. AB - The water quality of Mahisagar river, near Galteshwar in Kheda district of Gujarat, India, was assessed through a rapid integrated technique by physicochemical parameters as well as benthic macroinvertebrates. Physicochemical parameters retrieved were pH, color, conductivity, total solids, total suspended solids, total dissolved solids, chlorides, total hardness, calcium hardness, magnesium hardness, alkalinity, turbidity, ammoniacal nitrogen, chemical oxygen demand, biochemical oxygen demand, dissolved oxygen, sulfates, and nitrates. The biological indices calculated were BMWP (Bio Monitoring Working Party) score or saprobic score and sequential comparison index or diversity score. In total, 37 families were encountered along the studied river stretch. The findings indicate that the water quality of Mahisagar river at sampled locations is "slightly polluted." Moreover, the results of physicochemical analysis are also in consonance with the biological water quality criteria developed by Central Pollution Control Board. PMID- 27358998 TI - Landslides susceptibility change over time according to terrain conditions in a mountain area of the tropic region. AB - Susceptibility to landslides in mountain areas results from the interaction of various factors related to relief formation and soil development. The assessment of landslide susceptibility has generally taken into account individual events, or it has been aimed at establishing relationships between landslide-inventory maps and maps of environmental factors, without considering that such relationships can change in space and time. In this work, temporal and space changes in landslides were analysed in six different combinations of date and geomorphological conditions, including two different geological units, in a mountainous area in the north-centre of Venezuela, in northern South America. Landslide inventories from different years were compared with a number of environmental factors by means of logistic regression analysis. The resulting equations predicted landslide susceptibility from a range of geomorphometric parameters and a vegetation index, with diverse accuracy, in the study area. The variation of the obtained models and their prediction accuracy between geological units and dates suggests that the complexity of the landslide processes and their explanatory factors changed over space and time in the studied area. This calls into question the use of a single model to evaluate landslide susceptibility over large regions. PMID- 27358999 TI - Spatial and temporal variations in non-point source losses of nitrogen and phosphorus in a small agricultural catchment in the Three Gorges Region. AB - Losses of agricultural pollutants from small catchments are a major issue for water quality in the Three Gorges Region. Solutions are urgently needed. However, before pollutant losses can be controlled, information about spatial and temporal variations in pollutant losses is needed. The study was carried out in the Wangjiagou catchment, a small agricultural catchment in Fuling District, Chongqing, and the data about non-point source losses of nitrogen and phosphorus was collected here. Water samples were collected daily by an automatic water sampler at the outlets of two subcatchments from 2012 to 2014. Also, samples of surface runoff from 28 sampling sites distributed through the subcatchments were collected during 12 rainfall events in 2014. A range of water quality variables were analyzed for all samples and were used to demonstrate the variation in non point losses of nitrogen and phosphorus over a range of temporal and spatial scales and in different types of rainfall in the catchment. Results showed that there was a significant linear correlation between the mass concentrations of total nitrogen (TN) and nitrate (NO3-N) in surface runoff and that the relationship was maintained with changes in time. Concentrations of TN and NO3-N peaked after fertilizer was applied to crops in spring and autumn; concentrations decreased rapidly after the peak values in spring but declined slowly in autumn. N and P concentrations fluctuated more and showed a greater degree of dispersion during the spring crop cultivation period than those in autumn. Concentrations of TN and NO3-N in surface runoff were significantly and positively correlated with the proportion of the area that was planted with corn and mustard tubers, but were negatively correlated with the proportion of the area taken up with rice and mulberry plantations. The average concentrations of TN and NO3-N in surface runoff reached the highest level from the sampling points at the bottom of the land used for corn only, but lowest in rice fields. Slope gradient had a significant positive correlation with TN's and total phosphorus (TP)'s concentration losses. Concentrations of TN, NO3-N, and total phosphorus were significantly correlated with rainfall. Peak concentrations of ammoniacal nitrogen occurred during the fertilizer application period in spring and autumn. Different structures of land use types had a significant influence on the concentration losses of nitrogen and phosphorus; thus, using a reasonable way to adjust land use structure and spatial arrangement of whole catchment was an effective solution to control non-point source pollution of the Three Gorges Region. PMID- 27359000 TI - Assessment of groundwater quality using DEA and AHP: a case study in the Sereflikochisar region in Turkey. AB - This study investigated the spatial distribution of groundwater quality in Sereflikochisar Basin, in the Central Anatolian region of Turkey using different hydrochemical, statistical, and geostatistical methods. A total of 51 groundwater samples were collected from the observation wells in the study area to evaluate the characteristics of the groundwater quality. As a relatively simple and practical method, a groundwater quality index (GWQI) was developed to evaluate the overall groundwater quality. In this process, complex decision-making techniques such as analytic hierarchy process (AHP) and data envelopment analysis (DEA) were used. Based on these models, two new indices (A-GWQI and D-GWQI) were proposed. According to the D-GWQI score (from 0.6 to 1), water quality was classified in four categories as unsuitable (0.6-0.7), permissible (0.7-0.8), good (0.8-0.9), and excellent (0.9-1). The spatial distribution maps of the groundwater quality were created using the Kriging method. For each map, seven different semivariogram models were tested and the best-fitted model was chosen based on their root mean square standardized error. These maps showed that the areas with high groundwater quality were in the eastern and southern parts of the study area where the D-GWQI scores were greater than 0.8. Depending on the distance from the Salt Lake, the characteristics of groundwater changed from NaCl to NaHCO3 and CaHCO3 facies. This study shows how to determine the spatial distribution of the groundwater quality and identify the impact of salt lakes on the groundwater quality in inland aquifers. The findings of this study can be applied to ensure the quality of groundwater used for drinking and irrigation purposes in the study area. PMID- 27359002 TI - Hiring a nutritionist? PMID- 27359003 TI - Preserving patient safety. PMID- 27359001 TI - Cadmium and lead in seafood from the Aratu Bay, Brazil and the human health risk assessment. AB - This study aimed to evaluate cadmium (Cd) and lead (Pb) levels in seafood and perform a risk assessment based on individual food consumption frequency of inhabitants of the Aratu Bay, Brazil. From December 2013 to November 2014, ready to-market seafood, including fish [pititinga (Lile piquitinga) and small green eel (Gobionellus oceanicus)], mollusks [mussel (Mytella guyanensis) and oyster (Crassostrea rhizophorae)], and crustaceans [white shrimp (Litopenaeus schmitti) and blue crab (Callinectes exasperatus)], were purchased bimonthly from a local artisanal shellfish harvester. Metal levels were analyzed by graphite furnace atomic absorption spectrometry (GFAAS). Based on the volunteer' seafood consumption, estimates of the non-carcinogenic target hazard quotients (THQs) were calculated. The annual concentrations (MUg/g, w/w) of Cd were 0.007 (+/ 0.001) in crustaceans, 0.001 (+/-0.0003) in fish, and 0.446 (+/-0.034) in mollusks. Lead levels were =1 and <9.9. These data are important to inform the community of the imminent exposure risk through communication strategies, with the purpose of minimizing exposure and, consequently, the health effects associated with it. PMID- 27359004 TI - ICD-10 delay gives opportunity to take low-cost, high-impact steps to prepare for the new code set. PMID- 27359005 TI - DEVELOPMENT OF CHINESE HEALTH LAW: OVERVIEW AND SUGGESTIONS. AB - Health law is a rapidly developing law specialty in China. This article examines the current overall framework and evolution of Chinese health law, as a background to an analysis of the advantages and disadvantages of this legal regime. Research suggests that: 1) The independent status of Chinese health law as jurisprudence and a specialty ought to be assured altogether; 2) The convergence between health law and other laws should be strengthened; 3) The current Chinese health law framework ought to be completed. This suggests the necessity to find ways to improve the independence of health law in China by eliminating the convergence and completing the legal framework. PMID- 27359006 TI - THE WHO DEFINITION OF HEALTH: A CRITICAL READING. AB - The purpose of this article is to clarify the meaning of health, starting from the analysis of the definition of health stated by the World Health Organization (WHO) in 1948, highlighting its strengths and its critical aspects. The considerations on the opportunity to revise the definition of health, adapting it to the changed conditions of the world population, gave rise to a proposal for a new definition focused on the ability to adapt and self-manage in face of social, physical, and emotional challenges. Even though we recognize that adaptation and self-management are important qualities, we have to question the extrinsic conditions to which health is subordinate. Thus, if we evaluate this definition as suitable, we must clarify how health is necessarily linked to socio-economic and environmental policies, paying attention to the procedure to be followed in order to pass from what ought to be to what is. PMID- 27359007 TI - MKHITAR GOSH'S MEDIEVAL LAW CODE AND ITS IMPLICATIONS FOR ARMENIAN COMMUNITIES ABROAD. AB - The Law Book of the medieval Armenian legal and economic thought is an exceptional work that encompasses valuable information of the Armenian nation's domestic life. Mkhitar Gosh was considered to be one of the most outstanding figures and lawyers (lawmakers) of all times. Armenian Law Code after Mkhitar Gosh is writhed at 12 century. One of the primary sources for the law code was Armenian customary law. This Code became moral code for guiding for hall Armenians over the world because of high moral spirit reflecting Armenian mentality. This article presents the brief history of extension of legal rules setting out in the Law Code. The Law Code was established and widely used not only in Armenia but also in a number of Armenian communities abroad (Russian, Poland, Georgia, Latvia, India etc.). Law Code was accepted by all Armenians. Moreover, it served for the development of legislation for a number of civilized European and Asian countries. PMID- 27359008 TI - IS IT TIME TO TEACH MEDICAL ETHICS TO EMT'S? AN ISRAELI CASE STUDY. AB - In 2012, the Israeli actor and director Doron Nesher had a stroke and his family called the Israeli Emergency Service to take him to the hospital. On arrival, the medical crew encountered resistance by the patient who refused to receive treatment and to be accompanied to the hospital. After all of the crew's persuasion attempts that lasted about two hours failed, the crew left the scene without the patient, against his tearing wife's repeated requests. Hours later, the family, with the help of neighbors, took Mr. Nesher to the hospital in a private car, rolled up in a carpet. In this paper, I claim that the medical crew made an ethical error by not forcing the patient to go to the hospital. However, I do not blame the crew itself, but rather point my finger towards two institutional culprits: the Israeli Emergency Medical Service and the Israeli medical ethics education of paramedics and emergency medical technicians. I recommend that we start teaching medical ethics to paramedical professions. PMID- 27359009 TI - ANNOTATION TAKEN, IN THE PERSPECTIVE OF CRIMINAL AND CONSTITUTIONAL LAW, AS WELL AS IN CRIMINOLOGY, TO THE DECISION OF THE PORTUGUESE CONSTITUTIONAL COURT, OF JANUARY 13, 2011--WITH RESPECT TO THE PROBLEMS OF "CONSENT" AND "MEDICAL ACT". AB - 1--Summary of the decision taken by the Portuguese Constitutional Court, of January 13, 2011; 2--Complete text of the decision of the Portuguese Constitutional Court, of January 13, 2011, Judge Maria Joao ANTUNES (Reporter), Judge Carlos Pamplona de OLIVEIRA, Judge Jose Borges SOEIRO, Judge Gil GALVAO, Judge Rui Manuel Moura RAMOS (President)--in terms of the appositive declaration to the sentence n. 487/2010: t.c.http://www. tribunalconstitucional.pt, August 1, 2011; 3--Brief annotation to the problem of the "medical act"; 3.1--Plus some conclusions on the brief annotation to the problem of the "medical act"; 3.2- Brief annotation to the problem of "consent"--continuation of the previous comments; 4--Conclusions. It must never be forgotten that "consent" does not stand as the only cause of exclusion of unlawfulness. PMID- 27359010 TI - THE DUTY TO PERFORM A PATIENT RECALL. AB - In this article the so-called patient recall duty is discussed. More specifically, it has been determined if and when a physician should inform his former patients about newly discovered side effects relating to previously executed treatments. Although such an obligation may be surprising there are, in my view, sufficient arguments to justify the duty to perform a patient recall in some cases. The potential objections to the imposition of this duty do not alter my opinion. However, it is by no means the intention to impose on the physician a general post information obligation. In my opinion, two fundamental criteria should be taken into account in order to assess when the physician is obliged to carry out a patient recall, namely: the severity of the potential harm, and the foreseeability of the potential harm. This can be derived from similar existing criteria in other areas in which a recall obligation exists and from the case law concerning patient recall. PMID- 27359011 TI - HANNIBAL REVISITED: ANTISOCIAL PERSONALITY DISORDER VERSUS PSYCHOPATHY--MEDICO LEGAL PERSPECTIVES FROM SOUTH AFRICA. AB - Psychopathy and its relation to criminal behaviour has been the focus of clinical research for many years. Within the context of South African criminal law, the impact of psychopathy on criminal liability has been addressed in numerous decisions with varying outcomes all indicative of the reality that psychopathy will at most serve as a factor in mitigation of sentence, but will not exonerate an accused of criminal responsibility. In this contribution, the author reflects on the diagnostic entities of psychopathy and antisocial personality disorder against the backdrop of South African criminal law cases in terms of which either of these entities were raised in support of mitigation of sentence and/or as extenuating circumstances. PMID- 27359012 TI - INTRODUCTORY EDITORIAL. PMID- 27359013 TI - THE ETHICAL ISSUES IN THE RELATIONSHIP BETWEEN THE PSYCHOLOGIST AS THERAPIST AND THE PATIENT. AB - The two main ethical issues in the relationship between the psychotherapist and patient have been mentioned to be: Sexual involvement between the Psychologist and patient, and the dilemma of confidentiality so called the double loyalty of the therapist. This article will professionally discuss the nature and implications of these two phenomena; and it will propose preventive measures and strategies to cope with. PMID- 27359014 TI - PSYCHOLOGICAL IMPLICATIONS OF ILLNESS CONDITIONS AND PHYSICAL DISABILITIES, AND THEIR PLACE IN THE DISCOURSE--OR BETTER TO SAY: IN THE INTERACTION BETWEEN PHYSICIAN AND PATIENT. AB - This article is based on the idea that, in the dialogue between physician and patient, aside from determining "what kind of illness a person has", it is equally important to acknowledge "what kind of person stands behind the illness". This means that the psychological meaning denoted by the patient to the physician's explanations referring to his/her impaired medical condition, and nature of the disability, is most important in determining whether the patient will--in the psychological sense--perceive him/herself as handicapped. Basic concepts in the patient's coping process with the medical condition, and the proper adjustment to a possible disability are: adaptation to an adequate, new body image; awareness--as a cognitive procedure; acceptance--as an emotional entity. PMID- 27359015 TI - ADOPTION IN SHARI'A LAW, ITS IMPACT ON THE MUSLIM MINORITY IN ISRAEL, AND THE THERAPIST-PATIENT RELATIONSHIP WHEN PSYCHOLOGICAL INTERVENTION IS NECESSARY. AB - Adoption is an act of kindness and an expression of the most exalted of human morality. It fulfills the needs of both the adoptive parents and the adopted child. Muslim religious law has rejected the concept of adoption as it exists in the western world and presents several alternatives including personal liability, declaration of guardianship, bestowing a gift and leaving a last will and testament. Nevertheless, over the past 20 years, the Arab-Muslim population in Israel has developed a certain acceptance of the more typical concept of adoption and the willingness to accept the civil legislation that is applied in domestic courts in Israel. This gradual integration into Israeli society as well as the very act of adoption, which remains controversial, often creates the need for treatment, consultation and guidance for the adoptive family and the adopted child. The traditional, collective characteristics of the Arab-Muslim society have a significant impact on the child's emotional state and behavior and, of course, effect the adoptive family's social standing as well. In such situations, it is imperative to discuss the interaction and the often difficult and complex relationship that develops between the therapist or counselor and the patient. PMID- 27359016 TI - PATIENT'S RIGHTS LAW AND CULTURALLY COMPETENT NURSING CARE: AN ISRAELI PERSPECTIVE. AB - AIMS: The purpose of the current article is to discuss the culturally competent nursing practice according to the patient's rights law and to suggest strategies and models to facilitate culturally competent nursing care. BACKGROUND: According to the patient's rights law, health care providers have to inform the patient about his/her health condition by an understandable language that is also appropriate to their culture. However, communication with culturally and linguistically diverse patients has been known to be difficult. Cultural and linguistic differences may impede access to health care, accurate diagnosis, and effective treatment. The culturally competent nursing approach was suggested as the most appropriate way to minimize these difficulties. CONCLUSION: This paper contributes to nursing care quality by suggesting the best available standards and models of care and improving culturally appropriate care. Nurses should place cultural competence as a priority, and protect their patients' diverse cultural and ethnical rights. PMID- 27359017 TI - THE ADOPTION OF BUDDHISM'S PRINCIPLES AS A MEANS OF IMPROVING PHYSICIANS' WORK WITH TERMINALLY ILL PATIENTS. AB - The medical approach as summarized by Leibowitz--"We must treat the person, not just the disease"--highlights the importance of treating the sick person and not only the illness' pathology. This approach calls for healing not only the physical side, but also--and mainly--the mental aspect of the patient. One of the goals of this article is to turn physicians' attention towards the compassion necessary in treating a person with a severe or chronic illness, or a person who is dying--precisely because sometimes there is no medical cure for the physical state of such a patient. Therefore, physicians' attention does need to be directed to providing emotional assistance to such a patient. Sometimes, the emotional strength the patient draws from the medical team that is treating him can change his view of, and approach to, the illness, and can enable his body to muster the emotional strength necessary to deal with his situation. Buddhism's approach enables the sick patient to experience his illness in a different way, by making peace with one's situation and, sometimes, even viewing the situation differently--viewing the illness as a type of renewal. Buddhism, therefore, enables a sick person to choose a different point of view when his energy is exhausted and he loses hope, providing quality of life to patients. In such a situation, a sick person finds emotional strength in the knowledge that the end of his life is actually a renewal somewhere else. The limited life expectancy of the terminally ill patient demands that he be able to spend his time with minimal concerns and worries, and does not leave much time for treating the emotional side--the patient's fear. In light of this fact, the patient's ability to look ahead and grasp at hope is the most important issue. As much as possible, this is accomplished in an atmosphere of acceptance and with the absence, or reduction, of fear. The freedom to decide for oneself how to behave, according to one's own approach, is what makes it possible for the sick individual to feel empowered, and is liable to encourage the patient to adopt a different point of view. The Buddhist approach recommends replacing the helplessness that usually accompanies the predicament of terminally ill patients with acceptance of responsibility for their behavior in any given situation; this is Buddhism's main contribution to both physicians and patients alike. PMID- 27359018 TI - THE ROLE OF THE ISRAELI COURTS IN FORMULATING THE PHYSICIAN-PATIENT RELATIONSHIP. AB - The nature of physician-patient relationships has been documented in the ancient Greek and Roman, as well as in that of the Middle Ages and modern times' literature. Far back as in Hippocrates' writings, ethical dilemmas including those concerning patient-physician relationships, patient consent to treatment and end of life issues have been raised and discussed. Over time, changes have occurred in the dynamic between the diverse values that are taken into consideration when defining the therapeutic milieu. The nature of this dyad has have moved from a paternalistic framework empowering the physician and emphasizing the patient's wellbeing, to a relational framework that empowers the patient and is focused on his desires and rights. The pendulum of the physician patient relationship is continually adjusted, in each era, in accordance with contemporary social values and by norms that have been shaped by judicial tribunals and legislation. Viewing the issue of physician-patient relationship as an ethical dilemma deeply rooted within social-cultural contexts demands the formulation of a theoretical framework incorporating the relevant ethical principles and a system of implementation that constitutes a declaration of intention concerning the values we thereby wish to protect. The current state of affairs in which legal and legislative arrangements prefer patient autonomy above other significant social values, could provide the foundation for a more stable, appropriate and fruitful physician-patient relationship. This article wishes to critically examine the questions of whether and, in what ways, the law influences the character of the physician-patient relationship and the implications of such influence for medical policy and practice. In light of the lack of consistency of rulings in this domain, the necessity of adopting ethical guidelines through legislation and need for the legal system to constructively and systematically balance the diverse ethical approaches regarding the physician-patient relationship, becomes clear. PMID- 27359019 TI - THE BUDGET, THE FAMILY PHYSICIAN AND THE PATIENT A DIFFERENT APPROACH. AB - Modern medicine offers better health and longer life expectancy, yet consumes huge budgets. The Israeli Health Insurance Law (IHIL) regulates the delivery of health services to all Israel's residents through Health Maintenance Organizations (HMOS). These organizations confront constant struggles with their budgets and have to reduce expenses as much as possible (without harming the health level rendered). In the constant necessity to restrain expenses are embedded difficulties that might cause unrest to the Public Health System (PHS). At the edge of the public health spear are the Family Physicians (FPS) who have not only to supply the best possible medicine to their patients, and at the same time confront budgetary constraints that have the potential to hinder the level of rendered medicine, but also have, at times, to mediate between the conflicting interests of their patients' wish to receive the best available health measures, the FP own medical believes, the HMO's directives and, between the FPS wish, to keep up the number of their (content) patients. One of the World Health Organization's (WHO) concepts, like Israel's one, is that soul and body are inseparable and must be addressed simultaneously in the process of healing. Real life at the Family Physicians' clinics shows, at times, that despite the Israeli physicians' very high professional level, and the Israeli Health System (IHS)'s high efficiency, such a process, due to budgetary constraints, workload and various other reasons, does not always take place and, on the personal level, there are patients who feel that the "system" has treated them incorrectly and in an unsatisfactory manner. Unsatisfied and restless patients might cause undesirable consequences to the "system", like losing faith in one's FP and HMO, which might lead to the patients' reduced cooperation in the healing process, lawsuits amplification, patients leaving their FPS and their HMOs etc. Addressing the patient's soul and body as an inseparable unit would help harnessing the patients' will and mental resources to the healing process. A content and satisfied patient tends to less argue with his/her FP, to be more satisfied with the rendered health services, to be more grateful for the provided services, to be healthier (as some would argue), to be more motivated and committed to the healing process, thus, all parties would benefit, emotionally, physically and from the budgetary point of view. This article would like to offer a "simple" 'yet very effective way' to keep the HMO's members feel that they are not alone at their sensitive time of illness, that behind the FP's desk sits not only a professional figure, but also a "human being" who is there to support their "souls" as well, thus, harnessing the patients to the healing process, reducing the patients' possible discontent from the HMOS's ways of rendering services including, at times, in cases when the required or desired medical measures is not received. The correct use of Interpersonal Communication (IPC) by the FP encompasses tremendous opportunities to achieve the desired connection between soul and body during the healing process, and offers many personal, budgetary and other benefits to the patient, FP, HMO and the health system at large. Its use is almost costless, its contribution to the health system is huge and, last, but not least, it can easily be learned and adopted by FPS in their daily work with their patients and the system. PMID- 27359020 TI - EFFECTIVE COMMUNICATION AS AN IMPORTANT SKILL FOR QUALITY CARE IN ELDERLY PATIENTS. AB - The increase in the number of older people in the world emphasizes the need to reevaluate and change health care policy and care services priorities. The provision of health care for this growing population has consequently become an important worldwide concern. The purpose of this article is to highlight the challenges stemming from the growing number of elderly people and their need for care. Collaborative and coordinated health care services for elderly people should be focused on the ethical issues deriving from the interpersonal relationships between the professional caregiver and the older person. Any discussion on ethics and aging should be focused on the roles of autonomy, informed consent, respect, advance directive, end of life decisions and privacy. In addition, such a discussion should stress the important role of effective communication and its effect on the older person's adherence with the recommended treatment. The desired consequence should be the empowerment of positive and successful experiences attained by the recipients of the health care services. PMID- 27359021 TI - THERAPEUTIC COPING WITH ADHD AMONG CHILDREN FROM THE ARAB ISRAELI SECTOR WITH AN EMPHASIS ON THE THERAPIST-PATIENT RELATIONSHIP. AB - Over the past two decades, the Arab Israeli society's awareness to the need to treat children suffering from Attention Deficit/Hyperactivity Disorder (ADHD) has been rising. The State of Israel provides educational and psychological services in almost every Arab-Israeli town, allowing for identification, diagnosis and treatment. However, misleading prejudice stemming from lack of basic knowledge poses difficulties when offering appropriate therapy. The present paper aims to demonstrate the implications of such unawareness and stigmas, as well as to present the dilemmas and flaws in the professional relationship required between those involved in rendering appropriate care. It concludes that a multi-system therapeutic approach must be adopted by the Arab Israeli society, with emphasis placed on the therapist-patient relationship and the ability to take into consideration the individual needs of each case. PMID- 27359022 TI - EMOTIONAL INTELLIGENCE, MORAL, ETHICS, BIO-ETHICS AND WHAT IS IN BETWEEN. AB - In recent years, the study of emotions has broadened its scope and established its standing as a new scientific discipline. Humanity has become increasingly conscious of the seminal role played by the emotional components in both intrapersonal and interpersonal behavior. A deeply rooted and inherent correlation exists between emotional intelligence (E.I. - Emotional Intelligence) and positive social results: social adaptation, quality social relationships, the capacity for healthy social behaviors, caring, altruism, empathy, enlightened communication and the efficacy and personal coherence essential to moral and ethical behavior, including its manifestation in the sphere of bio-ethics. The importance of the personal relationship between the doctor and the patient is especially fundamental in the current era of immense and accelerated scientific technological development, forcing doctors to cope with an increasingly complicated technical environment. Precisely because of this reality, it is essential that a doctor's actions and interpersonal relationship with the patient proceed from an ethical base, grounded in both professional and emotional responsibility. Emotional responsibility is one of the central elements underlying bioethical conduct and is the element that provides the guideposts for the treatment of others. The symbiotic connection between emotional intelligence and the sphere of ethics and morals is what delineates human beings. Human beings, by definition and in essence, bear responsibility for their actions. The beginning of ethics is in the human being's consciousness of choice in relation to self and to others. An individual's choices integrate emotion and cognition. That ability to integrate alongside the capacity for choice enables the human race to act in accordance with ethical and moral codes. At work, on a daily basis, a doctor is positioned opposite to the physical, emotional, cognitive and ethical entirety of the patient. Beyond the doctor's technical ability to heal, there also exists his capacity to create within the patient the desire to heal. PMID- 27359035 TI - Pre-analytical standardization should be mandatory before reference ranges for mean platelet volume are determined. PMID- 27359036 TI - Substrate Stiffness Regulates the Development of Left-Right Asymmetry in Cell Orientation. AB - Left-right (LR) asymmetry of tissue/organ structure is a morphological feature essential for many tissue functions. The ability to incorporate the LR formation in constructing tissue/organ replacement is important for recapturing the inherent tissue structure and functions. However, how LR asymmetry is formed remains largely underdetermined, which creates significant hurdles to reproduce and regulate the formation of LR asymmetry in an engineering context. Here, we report substrate rigidity functioning as an effective switch that turns on the development of LR asymmetry. Using micropatterned cell-adherent stripes on rigid substrates, we found that cells collectively oriented at a LR-biased angle relative to the stripe boundary. This LR asymmetry was initiated by a LR-biased migration of cells at stripe boundary, which later generated a velocity gradient propagating from stripe boundary to the center. After a series of cell translocations and rotations, ultimately, an LR-biased cell orientation within the micropatterned stripe was formed. Importantly, this initiation and propagation of LR asymmetry was observed only on rigid but not on soft substrates, suggesting that the LR asymmetry was regulated by rigid substrate probably through the organization of actin cytoskeleton. Together, we demonstrated substrate rigidity as a determinant factor that mediates the self organizing LR asymmetry being unfolded from single cells to multicellular organization. More broadly, we anticipate that our findings would pave the way for rebuilding artificial tissue constructs with inherent LR asymmetry in the future. PMID- 27359041 TI - Epitaxial Growth of Single Layer Blue Phosphorus: A New Phase of Two-Dimensional Phosphorus. AB - Blue phosphorus, a previously unknown phase of phosphorus, has been recently predicted by theoretical calculations and shares its layered structure and high stability with black phosphorus, a rapidly rising two-dimensional material. Here, we report a molecular beam epitaxial growth of single layer blue phosphorus on Au(111) by using black phosphorus as precursor, through the combination of in situ low temperature scanning tunneling microscopy and density functional theory calculation. The structure of the as-grown single layer blue phosphorus on Au(111) is explained with a (4 * 4) blue phosphorus unit cell coinciding with a (5 * 5) Au(111) unit cell, and this is verified by the theoretical calculations. The electronic bandgap of single layer blue phosphorus on Au(111) is determined to be 1.10 eV by scanning tunneling spectroscopy measurement. The realization of epitaxial growth of large-scale and high quality atomic-layered blue phosphorus can enable the rapid development of novel electronic and optoelectronic devices based on this emerging two-dimensional material. PMID- 27359042 TI - IDD388 Polyhalogenated Derivatives as Probes for an Improved Structure-Based Selectivity of AKR1B10 Inhibitors. AB - Human enzyme aldo-keto reductase family member 1B10 (AKR1B10) has evolved as a tumor marker and promising antineoplastic target. It shares high structural similarity with the diabetes target enzyme aldose reductase (AR). Starting from the potent AR inhibitor IDD388, we have synthesized a series of derivatives bearing the same halophenoxyacetic acid moiety with an increasing number of bromine (Br) atoms on its aryl moiety. Next, by means of IC50 measurements, X-ray crystallography, WaterMap analysis, and advanced binding free energy calculations with a quantum-mechanical (QM) approach, we have studied their structure-activity relationship (SAR) against both enzymes. The introduction of Br substituents decreases AR inhibition potency but improves it in the case of AKR1B10. Indeed, the Br atoms in ortho position may impede these drugs to fit into the AR prototypical specificity pocket. For AKR1B10, the smaller aryl moieties of MK181 and IDD388 can bind into the external loop A subpocket. Instead, the bulkier MK184, MK319, and MK204 open an inner specificity pocket in AKR1B10 characterized by a pi-pi stacking interaction of their aryl moieties and Trp112 side chain in the native conformation (not possible in AR). Among the three compounds, only MK204 can make a strong halogen bond with the protein (-4.4 kcal/mol, using QM calculations), while presenting the lowest desolvation cost among all the series, translated into the most selective and inhibitory potency AKR1B10 (IC50 = 80 nM). Overall, SAR of these IDD388 polyhalogenated derivatives have unveiled several distinctive AKR1B10 features (shape, flexibility, hydration) that can be exploited to design novel types of AKR1B10 selective drugs. PMID- 27359043 TI - Target-selective tilt aftereffect during texture learning. AB - Sensory adaptation and perceptual learning are two forms of plasticity in the visual system, with some potential overlapping neural mechanisms and functional benefits. However, they have been largely considered in isolation. Here we examined whether extensive perceptual training with oriented textures (texture discrimination task, TDT) induces adaptation tilt aftereffects (TAE). Texture elements were oriented lines at -22.5 degrees (target) and 22.5 degrees (background). Observers were trained in 5 daily sessions on the TDT, with 800 1000trials/session. Thresholds increased within the daily sessions, showing within-session performance deterioration, but decreased between days, showing learning. To evaluate TAE, perceived vertical (0 degrees ) was measured prior to and after each daily session using a single line element. The results showed a TAE of ~1.5 degrees at retinal locations consistently stimulated by the target, but none at locations consistently stimulated by the background texture. Retinal locations equally stimulated by target and background elements showed a significant TAE (~0.7 degrees ), in a direction expected by target-driven sensory adaptation. Moreover, these locations showed increasing TAE persistence with training. Additional experiments with a modified target, in order to have balanced stimulation around the vertical direction in all target locations, confirmed the locality of the task-dependent TAE. The present results support a strong link between perceptual learning and local orientation-selective adaptation leading to TAE; the latter was shown here to be task and experience dependent. PMID- 27359044 TI - Revealing the time course of signals influencing the generation of secondary saccades using Aalen's additive hazards model. AB - Saccadic eye movements are frequently followed by smaller secondary saccades which are generally assumed to correct for the error in primary saccade landing position. However, secondary saccades can also occur after accurate primary saccades and they are often as small as microsaccades, therefore raising the need to further scrutinize the processes involved in secondary saccade generation. Following up a previous study, we analyzed secondary saccades using rate analysis which allows us to quantify experimental effects as shifts in distributions, therefore going beyond comparisons of mean differences. We use Aalen's additive hazards model to delineate the time course of key influences on the secondary saccade rate. In addition to the established effect of primary saccade error, we observed a time-varying influence of under- vs. overshooting - with a higher risk of generating secondary saccades following undershoots. Moreover, increasing target eccentricity influenced the programming of secondary saccades, therefore demonstrating that error-unrelated variables co-determine secondary saccade programs. Our results provide new insights into the generative mechanisms of small saccades during postsaccadic fixation that need to be accounted for by secondary saccade models. PMID- 27359045 TI - Porous Transition of Polyelectrolyte Film through Reaction-Induced Phase Separation Caused by Interaction with Specific Metal Ions. AB - We describe a novel method for the simple and eco-friendly fabrication of porous polyelectrolyte films. A polyelectrolyte with many amine groups undergoes structural transformation from a dense to a porous structure upon immersion in a specific metal ion solution. The porous transition was the result of a reaction induced phase separation, which was caused by the formation of new bonds between the polyelectrolyte and metal ions. This method enables control of the pore size of the porous structure in the nanoscale (54 nm) to microscale (1.63 MUm) range through variation of the concentration or type of metal ions in the solution. To the best of our knowledge, this is the first report illustrating wide-range control of the pore size of a porous polyelectrolyte structure achieved by metal ions. These porous polyelectrolyte films with adjustable pore size and metastable metal ions can be employed in applications such as adsorption and catalysis. PMID- 27359046 TI - Self-Sorting in the Formation of Metal-Organic Nanotubes: A Crucial Role of 2D Cooperative Interactions. AB - A mixture of ferrocene-based tetratopic pyridyl ligands FcL1 and FcL2 undergoes self-sorting upon competitive coordination with AgBF4, affording homomeric nanotubes FcNT1 and FcNT2 as a mixture. No mutual interference for the nanotubular growth occurred between FcNT1 and FcNT2 even when one of these ligands was used in large excess with respect to the other. 2D X-ray diffraction analysis of unidirectionally oriented nanotube samples, prepared by using the capillary technique, revealed that although FcL1 as reported previously stacks helically in the resulting nanotube FcNT1 FcL2 prefers to stack with no discernible helical twist in FcNT2. Such a difference in their stacking geometries is most likely a major reason for why mixed-ligand metal-organic nanotubes are not constructed upon competitive coordination of FcL1 and FcL2 with AgBF4. PMID- 27359047 TI - Mediators of the relation between sexual victimization and distress: Comparison to bereavement. AB - OBJECTIVE: The purposes of this research were (a) to examine relationship quality and neuroticism as mediators of the relation between past sexual victimization and current distress in 2 samples of college students and (b) to examine the specificity of the mediated effects by assessing whether these variables also mediated the relation between the most common potentially traumatic event in both samples (past bereavement) and current distress. This study improved on prior research by using longitudinal data, assessing multiple mediators, assessing specificity of mediated effects, and replicating results across 2 samples. METHOD: Participants in both studies were undergraduate students in psychology courses (Ns = 1,528 and 1,084, respectively). In both studies, sexual victimization, bereavement and the 2 mediators (relationship quality and neuroticism) were assessed at baseline, and distress was assessed at baseline and 2 months later using standard measures. RESULTS: Structural equation modeling was used to assess the indirect (mediated) effects of sexual victimization and bereavement on later distress through relationship quality and neuroticism, controlling for baseline distress. In Study 1, the indirect effects of sexual victimization on distress through relationship quality and neuroticism were both significant. In Study 2, only the indirect effects through neuroticism were significant. None of the indirect effects were significant for bereavement, suggesting that the mediators were specific to sexual victimization. CONCLUSIONS: Neuroticism was a consistent mediator of the relation between lifetime sexual victimization and current distress, suggesting that it may be an important target of intervention for those with a history of sexual victimization. (PsycINFO Database Record PMID- 27359048 TI - Graphene Oxide Nanosheets Disrupt Lipid Composition, Ca(2+) Homeostasis, and Synaptic Transmission in Primary Cortical Neurons. AB - Graphene has the potential to make a very significant impact on society, with important applications in the biomedical field. The possibility to engineer graphene-based medical devices at the neuronal interface is of particular interest, making it imperative to determine the biocompatibility of graphene materials with neuronal cells. Here we conducted a comprehensive analysis of the effects of chronic and acute exposure of rat primary cortical neurons to few layer pristine graphene (GR) and monolayer graphene oxide (GO) flakes. By combining a range of cell biology, microscopy, electrophysiology, and "omics" approaches we characterized the graphene-neuron interaction from the first steps of membrane contact and internalization to the long-term effects on cell viability, synaptic transmission, and cell metabolism. GR/GO flakes are found in contact with the neuronal membrane, free in the cytoplasm, and internalized through the endolysosomal pathway, with no significant impact on neuron viability. However, GO exposure selectively caused the inhibition of excitatory transmission, paralleled by a reduction in the number of excitatory synaptic contacts, and a concomitant enhancement of the inhibitory activity. This was accompanied by induction of autophagy, altered Ca(2+) dynamics, and a downregulation of some of the main players in the regulation of Ca(2+) homeostasis in both excitatory and inhibitory neurons. Our results show that, although graphene exposure does not impact neuron viability, it does nevertheless have important effects on neuronal transmission and network functionality, thus warranting caution when planning to employ this material for neurobiological applications. PMID- 27359049 TI - Multi-resolution multi-sensitivity design for parallel-hole SPECT collimators. AB - Multi-resolution multi-sensitivity (MRMS) collimator offering adjustable trade off between resolution and sensitivity, can make a SPECT system adaptive. We propose in this paper a new idea for MRMS design based on, for the first time, parallel-hole collimators for clinical SPECT. Multiple collimation states with varied resolution/sensitivity trade-offs can be formed by slightly changing the collimator's inner structure. To validate the idea, the GE LEHR collimator is selected as the design prototype and is modeled using a ray-tracing technique. Point images are generated for several states of the design. Results show that the collimation states of the design can obtain similar point response characteristics to parallel-hole collimators, and can be used just like parallel hole collimators in clinical SPECT imaging. Ray-tracing modeling also shows that the proposed design can offer varied resolution/sensitivity trade-offs: at 100 mm before the collimator, the highest resolution state provides 6.9 mm full width at a half maximum (FWHM) with a nearly minimum sensitivity of about 96.2 cps MBq( 1), while the lowest resolution state obtains 10.6 mm FWHM with the highest sensitivity of about 167.6 cps MBq(-1). Further comparisons of the states on image qualities are conducted through Monte Carlo simulation of a hot-spot phantom which contains five hot spots with varied sizes. Contrast-to-noise ratios (CNR) of the spots are calculated and compared, showing that different spots can prefer different collimation states: the larger spots obtain better CNRs by using the larger sensitivity states, and the smaller spots prefer the higher resolution states. In conclusion, the proposed idea can be an effective approach for MRMS design for parallel-hole SPECT collimators. PMID- 27359051 TI - Dual effect of histone H4 on prothrombin activation. AB - Essentials Prothrombin converts slowly to thrombin upon interaction with histone H4. Histone H4 may also affect the reactivity of prothrombin toward factor Xa. Histone H4 enhances or inhibits activation by factor Xa depending on cofactor Va. The results reveal an unanticipated dual effect of histone H4 on prothrombin activation by factor Xa. SUMMARY: Background Recent studies have documented the ability of prothrombin to convert to the mature protease thrombin upon interaction with histone H4. The effect is abrogated by mutation of the catalytic Ser and requires the Gla domain. Objectives To explore the effect of histone H4 on the reactivity of prothrombin to its physiological activator factor (F) Xa, free or assembled in the prothrombinase complex. Methods The effect of histone H4 on prothrombin activation by FXa and prothrombinase is studied with kinetic assays. The potential epitope of prothrombin recognizing histone H4 is explored with electrostatic calculations using recent crystal structures. Results and Conclusions Binding of histone H4 has a dual effect on prothrombin activation by FXa that is of mechanistic significance: it enhances the reaction > 10-fold in the absence of cofactor Va, but produces complete inhibition in the presence of cofactor. Histone H4 binding to prothrombin produces very slow autoactivation independent of the coagulation cascade and promotes slow thrombin generation by FXa in the absence of phospholipids. In addition, histone H4 has a rapid and drastic inhibitory effect on prothrombin activation by prothrombinase that is likely to dominate pathophysiology. PMID- 27359052 TI - Fukushima Daiichi-Derived Radionuclides in the Ocean: Transport, Fate, and Impacts. AB - The events that followed the Tohoku earthquake and tsunami on March 11, 2011, included the loss of power and overheating at the Fukushima Daiichi nuclear power plants, which led to extensive releases of radioactive gases, volatiles, and liquids, particularly to the coastal ocean. The fate of these radionuclides depends in large part on their oceanic geochemistry, physical processes, and biological uptake. Whereas radioactivity on land can be resampled and its distribution mapped, releases to the marine environment are harder to characterize owing to variability in ocean currents and the general challenges of sampling at sea. Five years later, it is appropriate to review what happened in terms of the sources, transport, and fate of these radionuclides in the ocean. In addition to the oceanic behavior of these contaminants, this review considers the potential health effects and societal impacts. PMID- 27359053 TI - Janadolide, a Cyclic Polyketide-Peptide Hybrid Possessing a tert-Butyl Group from an Okeania sp. Marine Cyanobacterium. AB - Janadolide, a new cyclic polyketide-peptide hybrid possessing a tert-butyl group, was isolated from an Okeania sp. marine cyanobacterium. The gross structure was elucidated by spectroscopic analyses, and the absolute configurations of the amino acid moieties were determined by acid hydrolysis and chiral-phase HPLC analyses. The absolute configuration of the two stereogenic centers in the polyketide moiety was elucidated based on a combination of degradation reactions and spectroscopic analyses including the phenyl-glycine methyl ester method. Janadolide showed potent antitrypanosomal activity with an IC50 value of 47 nM without cytotoxicity against human cells at 10 MUM. PMID- 27359054 TI - Prognostic significance of PLIN1 expression in human breast cancer. AB - Breast cancer is a heterogeneous disease associated with diverse clinical, biological and molecular features, presenting huge challenges for prognosis and treatment. Here we found that perilipin-1 (PLIN1) mRNA expression is significantly downregulated in human breast cancer. Kaplan-Meier analysis indicated that patients presenting with reduced PLIN1 expression exhibited poorer overall metastatic relapse-free survival (p = 0.03). Further Cox proportional hazard models analysis revealed that the reduced expression of PLIN1 is an independent predictor of overall survival in estrogen receptor positive (p < 0.0001, HR = 0.87, 95% CI = 0.81-0.92, N = 3,600) and luminal A-subtype (p = 0.02, HR = 0.88, 95% CI = 0.78-0.98, N = 1,469) breast cancer patients. We also demonstrated that the exogenous expression of PLIN1 in human breast cancer MCF-7 and MDA-MB-231 cells significantly inhibits cell proliferation, migration, invasion and in vivo tumorigenesis in mice. Together, these data provide novel insights into a prognostic significance of PLIN1 in human breast cancer and reveal a potentially new gene therapy target for breast cancer. PMID- 27359055 TI - Mutation profiling of 19 candidate genes in acute myeloid leukemia suggests significance of DNMT3A mutations. AB - We selected 19 significantly-mutated genes in AMLs, including FLT3, DNMT3A, NPM1, TET2, RUNX1, CEBPA, WT1, IDH1, IDH2, NRAS, ASXL1, SETD2, PTPN11, TP53, KIT, JAK2, KRAS, BRAF and CBL, and performed massively parallel sequencing for 114 patients with acute myeloid leukemias, mainly including those with normal karyotypes (CN AML). More than 80% of patients had at least one mutation in the genes tested. DNMT3A mutation was significantly associated with adverse outcome in addition to conventional risk stratification such as the European LeukemiaNet (ELN) classification. We observed clinical usefulness of mutation testing on multiple target genes and the association with disease subgroups, clinical features and prognosis in AMLs. PMID- 27359056 TI - Post-translational deregulation of YAP1 is genetically controlled in rat liver cancer and determines the fate and stem-like behavior of the human disease. AB - Previous studies showed that YAP1 is over-expressed in hepatocellular carcinoma (HCC). Here we observed higher expression of Yap1/Ctgf axis in dysplastic nodules and HCC chemically-induced in F344 rats, genetically susceptible to hepatocarcinogenesis, than in lesions induced in resistant BN rats. In BN rats, highest increase in Yap1-tyr357, p73 phosphorylation and Caspase 3 cleavage occurred. In human HCCs with poorer prognosis (< 3 years survival after partial liver resection, HCCP), levels of YAP1, CTGF, 14-3-3, and TEAD proteins, and YAP1 14-3-3 and YAP1-TEAD complexes were higher than in HCCs with better outcome (> 3 years survival; HCCB). In the latter, higher levels of phosphorylated YAP1 ser127, YAP1-tyr357 and p73, YAP1 ubiquitination, and Caspase 3 cleavage occurred. Expression of stemness markers NANOG, OCT-3/4, and CD133 were highest in HCCP and correlated with YAP1 and YAP1-TEAD levels. In HepG2, Huh7, and Hep3B cells, forced YAP1 over-expression led to stem cell markers expression and increased cell viability, whereas inhibition of YAP1 expression by specific siRNA, or transfection of mutant YAP1 which does not bind to TEAD, induced opposite alterations. These changes were associated, in Huh7 cells transfected with YAP1 or YAP1 siRNA, with stimulation or inhibition of cell migration and invasivity, respectively. Furthermore, transcriptome analysis showed that YAP1 transfection in Huh7 cells induces over-expression of genes involved in tumor stemness. In conclusion, Yap1 post-translational modifications favoring its ubiquitination and apoptosis characterize HCC with better prognosis, whereas conditions favoring the formation of YAP1-TEAD complexes are associated with aggressiveness and acquisition of stemness features by HCC cells. PMID- 27359059 TI - Climate warming and heat waves affect reproductive strategies and interactions between submerged macrophytes. AB - Extreme climatic events, such as heat waves, are predicted to increase in frequency and intensity during the next hundred years, which may accelerate shifts in hydrological regimes and submerged macrophyte composition in freshwater ecosystems. Since macrophytes are profound components of aquatic systems, predicting their response to extreme climatic events is crucial for implementation of climate change adaptation strategies. We therefore performed an experiment in 24 outdoor enclosures (400 L) separating the impact of a 4 degrees C increase in mean temperature with the same increase, that is the same total amount of energy input, but resembling a climate scenario with extreme variability, oscillating between 0 degrees C and 8 degrees C above present conditions. We show that at the moderate nutrient conditions provided in our study, neither an increase in mean temperature nor heat waves lead to a shift from a plant-dominated to an algal-dominated system. Instead, we show that species-specific responses to climate change among submerged macrophytes may critically influence species composition and thereby ecosystem functioning. Our results also imply that more fluctuating temperatures affect the number of flowers produced per plant leading to less sexual reproduction. Our findings therefore suggest that predicted alterations in climate regimes may influence both plant interactions and reproductive strategies, which have the potential to inflict changes in biodiversity, community structure and ecosystem functioning. PMID- 27359058 TI - Fulvestrant 500 mg vs 250 mg in postmenopausal women with estrogen receptor positive advanced breast cancer: a randomized, double-blind registrational trial in China. AB - The international CONFIRM study showed that fulvestrant 500 mg improved progression-free survival (PFS) vs fulvestrant 250 mg in postmenopausal women with estrogen receptor (ER)-positive locally advanced/metastatic breast cancer (LA/MBC). In this randomized, double-blind study, postmenopausal Chinese women with ER-positive LA/MBC and progression after endocrine therapy received fulvestrant 500 mg (days 0, 14, 28, and every 28 days thereafter) or fulvestrant 250 mg (every 28 days). Consistency with the international study was assumed if the hazard ratio (HR) for comparison of PFS (primary endpoint) was < 1 (stratified log-rank test). The study was not powered to assess between-group differences.In total, 221 patients were randomized (fulvestrant 500 mg: n = 111; fulvestrant 250 mg: n = 110). Baseline characteristics were balanced. Median PFS was 8.0 months with fulvestrant 500 mg vs 4.0 months with 250 mg (HR = 0.75; 95% confidence interval [CI] 0.54-1.03; P = 0.078). PFS (HR; 95% CI) favored fulvestrant 500 mg in post-antiestrogen (0.86; 0.54-1.37) and post-aromatase inhibitor (0.65; 0.42-1.03) settings. No new safety considerations were observed. These results are consistent with the international CONFIRM study, supporting the superior clinical benefit of fulvestrant 500 mg in women with ER-positive LA/MBC experiencing progression following prior endocrine therapy. PMID- 27359057 TI - MiR-223-5p works as an oncomiR in vulvar carcinoma by TP63 suppression. AB - MiR-223-5p has been previously mentioned to be associated with tumor metastasis in HPV negative vulvar carcinomas, such as in several other tumor types. In the present study, we hypothesized that this microRNA would be important in vulvar cancer carcinogenesis and progression. To investigate this, we artificially mimicked miR-223-5p expression in a cell line derived from lymph node metastasis of vulvar carcinoma (SW962) and performed in vitro assays. As results, lower cell proliferation (p < 0.01) and migration (p < 0.001) were observed when miR-223-5p was overexpressed. In contrast, increased invasive potential of these cells was verified (p < 0.004). In silico search indicated that miR-223-5p targets TP63, member of the TP53 family of proteins, largely described with importance in vulvar cancer. We experimentally demonstrated that this microRNA is capable to decrease levels of p63 at both mRNA and protein levels (p < 0.001, and p < 0.0001; respectively). Also, a significant inverse correlation was observed between miR-223-5p and p63 expressions in tumors from patients (p = 0.0365). Furthermore, low p63 protein expression was correlated with deeper tumor invasion (p = 0.0491) and lower patient overall survival (p = 0.0494). Our study points out miR-223-5p overexpression as a putative pathological mechanism of tumor invasion and a promising therapeutic target and highlights the importance of both miR-223-5p and p63 as prognostic factors in vulvar cancer. Also, it is plausible that the evaluation of p63 expression in vulvar cancer at the biopsy level may bring important contribution on prognostic establishment and in elaborating better surgical approaches for vulvar cancer patients. PMID- 27359061 TI - Nitrogen balancing and xylose addition enhances growth capacity and protein content in Chlorella minutissima cultures. AB - This study aimed to examine the metabolic changes in Chlorella minutissima cells grown under nitrogen-deficient conditions and with the addition of xylose. The cell density, maximum photochemical efficiency, and chlorophyll and lipid levels were measured. The expression of two photosynthetic proteins, ribulose-1,5 bisphosphate carboxylase/oxygenase (Rubisco) and the beta subunit (AtpB) of adenosine triphosphate synthase, were measured. Comparison of cells grown in medium with a 50% reduction in the nitrogen concentration versus the traditional medium solution revealed that the cells grown under nitrogen-deficient conditions exhibited an increased growth rate, higher maximum cell density (12.7*10(6)cellsmL(-1)), optimal PSII efficiency (0.69) and decreased lipid level (25.08%). This study has taken the first steps toward protein detection in Chlorella minutissima, and the results can be used to optimize the culturing of other microalgae. PMID- 27359060 TI - A new approach of microalgal biomass pretreatment using deep eutectic solvents for enhanced lipid recovery for biodiesel production. AB - The biomass of Chlorella sp. was pretreated with three different aqueous deep eutectic solvents (aDESs), i.e. aqueous choline chloride-oxalic acid (aCh-O), aqueous choline chloride-ethylene glycol (aCh-EG) and aqueous urea-acetamide (aU A). The effect of aDESs pretreatment of microalgae biomass was evaluated in terms of lipid recovery rate, total carbohydrate content, fatty acid composition, and thermal chemical behavior of biomass. Results indicated that, lipid recovery rate was increased from 52.03% of untreated biomass to 80.90%, 66.92%, and 75.26% of the biomass treated by aCh-O, aCh-EG and aU-A, respectively. However, there were no major changes observed in fatty acid profiles of both untreated and treated biomass, specifically palmitic acid, palmitoleic acid and stearic acid under various pretreatments. Furthermore, characterizations of untreated and treated biomass were carried out using Fourier transform infrared (FTIR), thermogravimetry analysis (TGA) and scanning electron microscope (SEM) to understand the enhanced lipids recovery. PMID- 27359062 TI - Inhibitory effects of CaO/Fe2O3 on arsenic emission during sewage sludge pyrolysis. AB - This work aimed to investigate effects and reaction mechanisms of CaO/Fe2O3 on emission behaviors of arsenic during sewage sludge pyrolysis. The results showed that 24.8-54.2%, 26.4-60.4% and 27.7-63.1% of arsenic escaped from three samples when pyrolysis process happened at 723, 923 and 1123K respectively. And the sludge which contained higher calcium and iron contents released less arsenic than others. External CaO and Fe2O3 were added into the sewage sludge to study their effects on arsenic emissions during pyrolysis, where both of them inhibited arsenic emission effectively, especially at high temperatures. With the help of thermogravimetry analysis and X-ray fluorescence, inhibitory mechanisms of CaO/Fe2O3 on arsenic emission during sewage sludge pyrolysis were studied. CaO could react with As2O3, As2S3 and NaAsO2 to form nonvolatile substances, such as Ca(AsO2)2; while Fe2O3 could react with NaAsO2 to generate certain substances which was stable below 1123K. PMID- 27359063 TI - Heat-treated Escherichia coli as a high-capacity biosorbent for tungsten anions. AB - Adsorption performance in the biosorption of tungsten using Escherichia coli cells can be significantly improved by using cell suspensions that have been heat treated at ?100 degrees C. In the case of E. coli cells suspension heated at 100 degrees C, the aqueous tungsten ions concentration rapidly decreased from 0.8mmol/L to practically zero within 1h. This biosorption time is much shorter than that of non-heat treated E. coli cells (7h). Furthermore, the adsorption saturation amount for cells heat-treated at 100 degrees C was significantly increased up to 1.62mmol-W/g-E. coli compared to the unheated E. coli cells case (0.62mmol-W/g-E. coli). Determination of the surface potential and surface structure along with quantitative analyses of free amino acids of heat-treated E. coli cells were also carried out and revealed that heated cells have a high zeta potential and express a higher concentration of amino acids on the cell surface. PMID- 27359064 TI - Removal performance and microbial communities in a sequencing batch reactor treating hypersaline phenol-laden wastewater. AB - Hypersaline phenol-rich wastewater is hard to be treated by traditional biological systems. In this work, a sequencing batch reactor was used to remove phenol from hypersaline wastewater. The removal performance was evaluated in response to the variations of operating parameters and the microbial diversity was investigated by 454 pyrosequencing. The results showed that the bioreactor had high removal efficiency of phenol and was able to keep stable with the increase of initial phenol concentration. DO, pH, and salinity also affected the phenol removal rate. The most abundant bacterial group was phylum Proteobacteria in the two working conditions, and class Gammaproteobacteria as well as Alphaproteobacteria was predominant subgroup. The abundance of bacterial clusters was notably different along with the variation of operation conditions, resulting in changes of phenol degradation rates. The high removal efficiency of phenol suggested that the reactor might be promising in treating phenol-laden industrial wastewater in high-salt condition. PMID- 27359065 TI - Fermentative lactic acid production from coffee pulp hydrolysate using Bacillus coagulans at laboratory and pilot scales. AB - In this study, the lignocellulosic residue coffee pulp was used as carbon source in fermentative l(+)-lactic acid production using Bacillus coagulans. After thermo-chemical treatment at 121 degrees C for 30min in presence of 0.18molL(-1) H2SO4 and following an enzymatic digestion using Accellerase 1500 carbon-rich hydrolysates were obtained. Two different coffee pulp materials with comparable biomass composition were used, but sugar concentrations in hydrolysates showed variations. The primary sugars were (gL(-1)) glucose (20-30), xylose (15-25), sucrose (5-11) and arabinose (0.7-10). Fermentations were carried out at laboratory (2L) and pilot (50L) scales in presence of 10gL(-1) yeast extract. At pilot scale carbon utilization and lactic acid yield per gram of sugar consumed were 94.65% and 0.78gg(-1), respectively. The productivity was 4.02gL(-1)h(-1). Downstream processing resulted in a pure formulation containing 937gL(-1)l(+) lactic acid with an optical purity of 99.7%. PMID- 27359066 TI - Arbuscular mycorrhizal symbiosis-mediated tomato tolerance to drought. AB - A multidisciplinary approach, involving eco-physiological, morphometric, biochemical and molecular analyses, has been used to study the impact of two different AM fungi, i.e. Funneliformis mosseae and Rhizophagus intraradices, on tomato response to water stress. Overall, results show that AM symbiosis positively affects the tolerance to drought in tomato with a different plant response depending on the involved AM fungal species. PMID- 27359068 TI - Addicted to blame. PMID- 27359067 TI - Systems analysis of the prostate transcriptome in African-American men compared with European-American men. AB - AIM: African-Americans (AA) have increased prostate cancer risk and a greater mortality rate than European-Americans (EA). AA exhibit a high prevalence of vitamin D deficiency. We examined the global prostate transcriptome in AA and EA, and the effect of vitamin D3 supplementation. PATIENTS & METHODS: Twenty-seven male subjects (ten AA and 17 EA), slated to undergo prostatectomy were enrolled in the study. Fourteen subjects received vitamin D3 (4000 IU daily) and 13 subjects received placebo for 2 months prior to surgery. RESULTS: AA show higher expression of genes associated with immune response and inflammation. CONCLUSION: Systems level analyses support the concept that Inflammatory processes may contribute to disease progression in AA. These transcripts can be modulated by a short course of vitamin D3 supplementation. PMID- 27359069 TI - Direct oral anticoagulants for venous thromboembolism treatment and prophylaxis. AB - Direct oral anticoagulants are a popular option for prevention and treatment of venous thromboembolism. However, they possess significantly different pharmacologic properties from warfarin. This article reviews approved direct oral anticoagulants, their indications, pharmacologic properties, monitoring, and reversal strategies. PMID- 27359070 TI - REC8 density along chromosomes prevents illegitimate synapsis. PMID- 27359072 TI - The association between angiogenic markers and fetal sex: Implications for preeclampsia research. AB - OBJECTIVE: Current research suggests sexual dimorphism between the male and female fetoplacental units, but with unknown relevance for preeclampsia. We investigated the association between fetal sex and concentrations of the angiogenic markers soluble Fms-like kinase 1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio in first and second-third trimester in women with/without preeclampsia, and the impact of fetal sex on the prognostic value of angiogenic markers for preeclampsia. STUDY DESIGN: Observational study in a prospective, population-based cohort of 2110 singleton pregnancies with 150 preeclampsia cases. RESULTS: Higher sFlt-1 concentrations were observed for women carrying female fetuses in first trimester (all, 1107.65 vs. 992.27pg/ml; preeclampsia cases, 1118.79 vs. 934.49pg/ml, p<0.05) and in second-third trimester (all, 1130.03 vs. 1043.15pg/ml; preeclampsia, 1480.30 vs. 1152.86pg/ml, p<0.05), with similar findings for the sFlt-1/PlGF ratio concentrations in first (29.67 vs. 27.39 p<0.05) and second-third trimester (3.56 vs. 3.22, p<0.05). In first trimester, log transformed concentrations of PlGF, sFlt-1 and sFlt-1/PlGF (all participants) and sFlt-1 (preeclampsia cases) associated with fetal sex in adjusted analyses (p<0.05). In second-third trimester, only log(sFlt-1) associated with fetal sex (all, p=0.028; preeclampsia, p=0.067) In receiver operating curve analysis, prediction of early-onset preeclampsia by sFlt-1/PlGF tended to be superior in pregnancies with female vs. male fetuses (p=0.06). CONCLUSION: Sexual dimorphism was observed for concentrations of angiogenic markers. Female fetal sex was associated to higher sFlt-1 and sFlt-1/PlGF ratio concentrations in both healthy pregnancies and women developing preeclampsia. Fetal sex should be considered in research and clinical use of angiogenic markers. PMID- 27359071 TI - Haemophilic pseudotumour in two parts of the maxilla: case report. AB - Haemophilic pseudotumour is a rare disease that occurs most often in femur, tibia, ilium or pelvic bone of a patient with haemophilia. Thus far, there have been only 31 reported cases in jaw bones and paranasal sinuses. Among them, the mandible is a more common site than the maxilla or paranasal sinuses. Here, we report a case of haemophilic pseudotumour in two parts of the maxilla. Contrast enhanced CT showed an expansive and thinly corticated lesion with fluid attenuation at the left anterior maxilla which seemed like a post-operative maxillary cyst, ameloblastoma or odontogenic cyst. In addition, the thickened left palatal process of the maxilla seemed like fibrous dysplasia or intraosseous vascular malformation. Since haemophilic pseudotumour is not pathognomonic in radiological findings, when a patient who suffered from haemophilia or had taken anticoagulating agents has jaw lesion, haemophilic pseudotumour should be included in a differential diagnosis. PMID- 27359074 TI - Explorative innovators and flexible use of social information in common ravens (Corvus corax) and carrion crows (Corvus corone). AB - Innovation and social information use are influenced by individual characteristics, and are important for the creation and transmission of novel behavioral patterns. Here, we investigated which individual factors predict innovation rates and social transmission of information in a comparative study with identically reared common ravens (Corvus corax) and carrion crows (Corvus corone corone; Corvus corone cornix). In the innovation experiment (1), we presented the birds with a novel problem-solving task while alone, to determine which individuals would quickly solve ("innovators") or not solve ("noninnovators") this task. We then related these findings to sex, object exploration (frequency of novel item manipulation), object neophobia (latency to novel item interaction), and social rank position. We found that innovators were more explorative than noninnovators, although they did not differ significantly in social rank, object neophobia or sex. In the social information use experiments (2 & 3), subjects first observed a model (Exp. 2: conspecific, heterospecific; Exp. 3: conspecific innovator & noninnovator) demonstrate a specific color selection in a 2-choice cup task, before being allowed to make their own cup selection. Innovator and noninnovator observers did not significantly differ in their tendency to use social information, that is, to select the demonstrated cup first, from a conspecific or heterospecific model. Furthermore, observers did not preferentially use social information from an innovator over a noninnovator model. We discuss our findings in relation to the likely benefits of flexible information use, and the role of other model characteristics, such as relationships, on the use of social information. (PsycINFO Database Record PMID- 27359073 TI - Assessment of the HScore for reactive haemophagocytic syndrome in patients with rheumatic diseases. AB - OBJECTIVES: Reactive haemophagocytic syndrome (RHS) is a hyperinflammatory disorder often occurring in the background of several disorders such as infections, malignancies, and rheumatic diseases. Recently, a score known as the HScore was developed for the diagnosis of RHS. In the original study, most of the patients had underlying haematological malignancy or infection and the best cut off value for the HScore was 169 (sensitivity 93%; specificity 86%). In this study we aimed to analyse the performance of the HScore in rheumatic disease related RHS. METHOD: The patients with rheumatic disorders evaluated in the Departments of Rheumatology and Paediatric Rheumatology at Hacettepe University, Ankara, Turkey between 2002 and 2014 were reviewed retrospectively. The first group (n = 30) consisted of patients with RHS; the control group (n = 64) included patients with active rheumatic diseases without RHS. RESULTS: In the RHS group, 14 (46.7%) had adult-onset Still's disease (AOSD), 10 (33.3%) systemic juvenile idiopathic arthritis (SJIA), and six (20%) systemic lupus erythematosus (SLE). The control group (n = 64) consisted of 32 (50%) AOSD, 13 (20.3%) SJIA, and 19 (29.7%) SLE patients. Applying the HScore to the RHS patients, the best cut-off value was 190.5 with a sensitivity of 96.7% and specificity of 98.4%. When we excluded the patients from the control group who had not had bone marrow aspiration (n = 23), the same cut-off (190.5) performed best (sensitivity 96.7%; specificity 97.6%). Applying the 2004 haemophagocytic lymphohistiocytosis (HLH 2004) criteria gave a sensitivity of 56.6% and a specificity of 100% in the whole study group. CONCLUSIONS: In our study, a cut-off value for the HScore different from the original study performed better. Further studies are warranted to determine optimum cut-off values in different studies. PMID- 27359075 TI - Lateral bias and temperament in the domestic cat (Felis silvestris). AB - Research points to a relationship between lateralization and emotional functioning in humans and many species of animal. The present study explored the association between paw preferences and emotional functioning, specifically temperament, in a species thus far overlooked in this area, the domestic cat. Thirty left-pawed, 30 right-pawed, and 30 ambilateral pet cats were recruited following an assessment of their paw preferences using a food-reaching challenge. The animals' temperament was subsequently assessed using the Feline Temperament Profile (FTP). Cats' owners also completed a purpose-designed cat temperament (CAT) scale. Analysis revealed a significant relationship between lateral bias and FTP and CAT scale scores. Ambilateral cats had lower positive (FTP+) scores, and were perceived as less affectionate, obedient, friendly, and more aggressive, than left or right-pawed animals. Left and right pawed cats differed significantly on 1 trait on the CAT scale, namely playfulness. The strength of the cats' paw preferences was related to the animals' FTP and CAT scores. Cats with a greater strength of paw preference had higher FTP+ scores than those with a weaker strength of paw preference. Animals with stronger paw preferences were perceived as more confident, affectionate, active, and friendly than those with weaker paw preferences. Results suggest that motor laterality in the cat is strongly related to temperament and that the presence or absence of lateralization has greater implications for the expression of emotion in this species than the direction of the lateralized bias. (PsycINFO Database Record PMID- 27359076 TI - No child is an island: ethical considerations in end-of-life care for children and their families. AB - PURPOSE OF REVIEW: Ethical challenges are commonly encountered when caring for children with life-threatening conditions. RECENT FINDINGS: Controversial end-of life issues, such as physician-assisted death and medical futility, may also arise in children. The approach to these issues in children may be guided by the 'adult' medical literature; the age of the patient should not be a relevant factor in determining the morality of these acts. As such, the focus of this review is on ethical issues unique to children and adolescents by nature of their dependence on their parents. Appreciation that child well-being is best promoted when care aligns with parental beliefs, values and culture has given rise to the practice of family-centred care, which we prefer to call 'family-partnered' care. Occasionally, a family-partnered approach may challenge fundamental paediatric ethical principles, including best interests, developing autonomy, and the importance of honesty and truth-telling. SUMMARY: This article explores the challenges that may arise when there is disagreement between the child, the parents, and the healthcare providers about care at the end-of-life and provides suggestions to clinicians about how to help resolve these conflicts. PMID- 27359077 TI - A positive risk approach when clients choose to live at risk: a palliative case discussion. AB - PURPOSE OF REVIEW: The article discusses recent approaches in the literature about clients who chose to live at risk in their homes. It argues for a positive risk-based approach and a tool to help manage risk in the home, and applies these to a hypothetical end-of-life scenario. RECENT FINDINGS: Historically, safety plans to consider risk management involved a culture of risk aversion supported by sometimes paternalistic motives intended to protect vulnerable clients. New findings in the literature engage in a process that respects the ethical principles underlying harm reduction philosophies. The literature also argues for a perspective that moves away from viewing risk as only harmful, to one that supports a positive understanding of risk as part of a client's informed choice. SUMMARY: A risk support management plan, based on a positive approach, can provide a way to both support a client's choice to live at risk, anticipate for expected complications, and inform the creation of a contingency plan to address concerns as they may arise. The added value of a structured approach like the one proposed here for risk support management plans is that it provides adequate due diligence and informed decision-making when planning for risk-taking in complex situations. PMID- 27359078 TI - Chronic breathlessness: silent and deadly. PMID- 27359080 TI - Cold-knife conisation and large loop excision of transformation zone significantly increase the risk for spontaneous preterm birth: a population-based cohort study. AB - OBJECTIVES: Our aim was to explore the association between cold-knife conisation and large loop excision of transformation zone (LLETZ) with spontaneous preterm birth in a large 10-year national sample. We wanted to explore further the association of these procedures with preterm birth according to gestation. STUDY DESIGN: We conducted a population based retrospective cohort study, using data from national Medical Birth Registry. The study population consisted of all women giving birth to singletons in the period 2003-2012 in Slovenia, excluding all induced labors and elective cesarean sections before 37 weeks of gestation (N=192730). We compared the prevalence of spontaneous preterm births (before 28 weeks, before 32 weeks, before 34 weeks and before 37 weeks of gestation) in women with cold-knife conisation or LLETZ compared to women without history of conisation, calculating odds ratios (OR), adjusted for potential confounders. Chi square test was used for descriptive analysis. Logistic regression analyses were performed to estimate crude odds ratio (OR) and adjusted odds ratio (aOR) and their 95% confidence intervals (95% CI) with two-sided probability (p) values. RESULTS: A total of 8420 (4.4%) women had a preterm birth before 37 weeks of gestation, 2250 (1.2%) before 34 weeks of gestation, 1333 (0.7%) before 32 weeks of gestation and 603 (0.3%) before 28 weeks of gestation. A total of 4580 (2.4%) women had some type of conisation in their medical history: 2083 (1.1%) had cold knife conisation and 2498 (1.3%) had LLETZ. In women with history of cold-knife conisation, the adjusted OR for preterm birth before 37 weeks of gestation was 3.13 (95% CI; 2.74-3.57) and for preterm birth before 28 weeks of gestation 5.96 (95% CI; 4.3-8.3). In women with history of LLETZ, the adjusted OR was 1.95 (95% CI; 1.68-2.25) and 2.88 (95% CI; 1.87-4.43), respectively. CONCLUSIONS: Women with cervical excision procedure of any kind have significantly increased odds for preterm birth, especially for preterm birth before 28 weeks and before 32 weeks of gestation. PMID- 27359079 TI - Associations between parameters of flow-mediated vasodilatation obtained by continuous measurement approaches and the presence of coronary artery disease and the severity of coronary atherosclerosis. AB - We investigated the associations between the parameters of flow-mediated vasodilatation (FMD) obtained by continuous measurement approaches and the presence of coronary artery disease (CAD) and the severity of coronary atherosclerosis. The subjects consisted of 282 consecutive patients who underwent coronary angiography (CAG) and in whom we could measure FMD. Using continuous measurement approaches, we measured FMD as the magnitude of the percentage change from brachial artery diameter from baseline to peak (bFMD), the maximum FMD rate calculated as the maximal slope of dilation (FMD-MDR), and the integrated FMD response calculated as the area under the dilation curve during the 60- and 120 s dilation periods (FMD-AUC60 and FMD-AUC120). We divided the patients into two groups, the CAD group and the non-CAD group, and defined the severity of coronary atherosclerosis according to the Gensini score. The CAD group showed significantly lower %FMD, FMD-MDR, FMD-AUC60, and FMD-AUC120. Gender, smoking, dyslipidemia (DL), and diabetes mellitus (DM), in addition to FMD-AUC120, were identified as significant independent variables that predicted the presence of CAD by a multivariate logistic regression. In addition, a multiple regression analysis indicated that gender, DL, and hypertension, in addition to FMD-AUC120, were predictors of the Gensini score. Finally, we defined the cutoff value of FMD AUC120 for the prediction of CAD in all patients as 11.1 (sensitivity 0.582, specificity 0.652) by a receiver-operating characteristic (ROC) curve analysis. In conclusion, FMD-AUC120 as assessed by continuous measurement approaches may be a superior marker for evaluating the presence of CAD and the severity of coronary atherosclerosis. PMID- 27359081 TI - Parasitic leiomyomas: a systematic review. AB - BACKGROUND: Parasitic leiomyomas were first described as early as 1909 but are a rare condition. In recent years, due to the rise of laparoscopic surgery and power morcellation, several cases of parasitic leiomyomas associated with this surgical procedure have been reported. METHODS: A literature search was performed using PubMed, Embase and Google Scholar with the following combination of keywords: leiomyoma OR uterine neoplasms OR uterine myomectomy OR laparoscopy OR hysterectomy OR peritoneal neoplasms AND parasitic. Papers describing parasitic leiomyomas were included. The results of these studies are summarized herein. RESULTS: We retrieved abstracts of 756 papers. Of these, 591 were excluded for not fulfilling the inclusion criteria and 54 were removed as duplicates; after full-text assessment, 8 were rejected for presenting cases of malignancy and finally 103 were included in our systematic review. From these, we present information about 274 patients with parasitic leiomyomas. The mean age of women was 40 years (range 18-79 years); and 154 (56%) had no history of uterine surgery, the others (120, 44%) having had a previous myomectomy or hysterectomy. Of the total, 106 (39%) women had a history of power morcellation. The most frequent clinical symptom was abdominal pain (49%) and the most frequent presentation was disseminated peritoneal leiomyomatosis. CONCLUSIONS: While parasitic leiomyoma was first described a century ago, the recent introduction of laparoscopic power morcellation has increased the number of reported cases. PMID- 27359082 TI - Prenatal detection of major congenital heart disease - optimising resources to improve outcomes. AB - INTRODUCTION: Congenital heart disease (CHD) is the most common major structural fetal abnormality and the benefits of prenatal detection are well described. The objective of this study was to evaluate the precision of prenatal diagnosis at a single tertiary referral unit over two three year periods (2006, 2007, 2008 and 2010, 2011, 2012), before and after a prenatal screening protocol for CHD was developed to include extended cardiac views, mandatory recall for suboptimal views, and a multidisciplinary Fetal Cardiac clinic was established. There exists a single national centre for paediatric cardiothoracic surgery in Ireland, a situation which facilitates near complete case ascertainment. MATERIALS AND METHODS: Surgery records of the National Children's Cardiac Centre were interrogated for all cases of major congenital heart defects requiring surgical intervention in the first six months of life. Minor procedures such as ligation of a patent ductus arteriosus and isolated atrial septal defect repairs were excluded. Analyses of the Fetal Medicine database at the Rotunda Hospital (a stand-alone tertiary level perinatology centre with 8500 deliveries per year) and the mortality data at the Perinatal Pathology department were conducted. The Cochrane-Armitage trend test was used to determine statistical significance in prenatal detection rates over time. RESULTS: 51,822 women delivered during the study period, and the incidence of major congenital heart disease either that underwent surgical intervention or that resulted in perinatal mortality, was 238/51,822 (0.5%). Prenatal detection of major CHD increased from 31% to 91% (p<0.001). Detection of critical duct-dependant lesions rose from 19% to 100%. CONCLUSION: We attribute the dramatic improvement in prenatal detection rates to the multifaceted changes introduced during the study period. Improved prenatal detection for births that are geographically remote from the National Paediatric Cardiac Centre will require local replication of this prenatal programme. PMID- 27359083 TI - Therapeutic targeting of Toll-like receptors: a review of Toll-like receptors and their signaling pathways in psoriasis. AB - INTRODUCTION: Expression of various Toll-like receptors (TLR) in keratinocytes (KCs) has offered new insights into the pathogenesis of psoriasis. When plasmacytoid dendritic cells (pDCs) are scarce in established psoriatic lesions, KCs take the responsibility to secrete IFN type 1 through TLR9 activation. Antagonists of TLR7 and TLR8 and anti-IL-12/IL-23 substances have shown promising results in treating psoriasis. Areas covered: References in this study were extracted from Scopus, PubMed and Embase databases by the search term: ('Toll Like Receptors' OR 'TLR') AND ('Psoriasis' OR 'Arthritis, Psoriatic' OR 'PsA'). Expert commentary: As the prevailing cell type, KCs play a major role in the maintenance of psoriatic lesions. By specific upregulation of IL-36 R, KCs can start the IL-23/IL-12 axis, leading to production of major culprits of psoriatic phenotype IL-17 and IL-22. Targeting IL-36 R could be considered as a new therapeutic target to eliminate cutaneous manifestations of psoriasis. PMID- 27359084 TI - Programmed death ligand 1 expression in hepatocellular carcinoma: Relationship With clinical and pathological features. AB - : The prognosis of hepatocellular carcinoma (HCC) remains poor, with only one third of patients eligible for curative treatments and very limited survival benefits with the use of sorafenib, the current standard of care for advanced disease. Recently, agents targeting the programmed death ligand 1 (PD L1)/programmed death receptor 1 (PD-1) immune checkpoint were shown to display impressive antitumor activity in various solid or hematological malignancies, including HCC. PD-L1 immunohistochemical expression is thought to represent a biomarker predictive of drug sensitivity. Here, we investigated PD-L1 expression in a series of 217 HCCs and correlated our results with clinical and histological features and immunohistochemical markers (PD-1, cytokeratin 19, glutamine synthetase, and beta-catenin expression). PD-L1 expression by neoplastic cells was significantly associated with common markers of tumor aggressiveness (high serum alpha-fetoprotein levels, P = 0.038; satellite nodules, P < 0.001; macrovascular invasion, P < 0.001; microvascular invasion, P < 0.001; poor differentiation, P < 0.001) and with the progenitor subtype of HCC (cytokeratin 19 expression, P = 0.031). High PD-L1 expression by inflammatory cells from the tumor microenvironment also correlated with high serum alpha-fetoprotein levels (P < 0.001), macrovascular invasion (P = 0.001), poor differentiation (P = 0.001), high PD-1 expression (P < 0.001), and the so-called lymphoepithelioma like histological subtype of HCC (P = 0.003). CONCLUSION: PD-L1 expression by either neoplastic or intratumoral inflammatory cells is related to tumor aggressiveness and suggests that the response to treatments targeting the PD L1/PD-1 immune checkpoint could be restricted to particular HCC variants; thus, enrichment of these tumor subtypes in future clinical trials should be considered. (Hepatology 2016;64:2038-2046). PMID- 27359086 TI - Functional Analysis of a Bacterial Antifreeze Protein Indicates a Cooperative Effect between Its Two Ice-Binding Domains. AB - Antifreeze proteins make up a class of ice-binding proteins (IBPs) that are possessed and expressed by certain cold-adapted organisms to enhance their freezing tolerance. Here we report the biophysical and functional characterization of an IBP discovered in a bacterium recovered from a deep glacial ice core drilled at Vostok Station, Antarctica (IBPv). Our study showed that the recombinant protein rIBPv exhibited a thermal hysteresis of 2 degrees C at concentrations of >50 MUM, effectively inhibited ice recrystallization, and enhanced bacterial viability during freeze-thaw cycling. Circular dichroism scans indicated that rIBPv mainly consists of beta strands, and its denaturing temperature was 53.5 degrees C. Multiple-sequence alignment of homologous IBPs predicted that IBPv contains two ice-binding domains, a feature unique among known IBPs. To examine functional differences between the IBPv domains, each domain was cloned, expressed, and purified. The second domain (domain B) expressed greater ice binding activity. Data from thermal hysteresis and gel filtration assays supported the idea that the two domains cooperate to achieve a higher ice binding effect by forming heterodimers. However, physical linkage of the domains was not required for this effect. PMID- 27359087 TI - What women want in their sperm donor: A study of more than 1000 women's sperm donor selections. AB - Reproductive medicine and commercial sperm banking have facilitated an evolutionary shift in how women are able to choose who fathers their offspring, by notionally expanding women's opportunity set beyond former constraints. This study analyses 1546 individual reservations of semen by women from a private Australian assisted reproductive health facility across a ten year period from 2006 to 2015. Using the time that each sample was available at the facility until reservation, we explore women's preference for particular male characteristics. We find that younger donors, and those who hold a higher formal education compared to those with no academic qualifications are more quickly selected for reservation by women. Both age and education as proxies for resources are at the centre of Parental Investment theory, and our findings further build on this standard evolutionary construct in relation to female mate preferences. Reproductive medicine not only provides women the opportunity to become a parent, where previously they would not have been able to, it also reveals that female preference for resources of their potential mate (sperm donor) remain, even when the notion of paternal investment becomes redundant. These findings build on behavioural science's understanding of large-scale decisions and human behaviour in reproductive medical settings. PMID- 27359085 TI - Influenza A (H1N1pdm09)-Related Critical Illness and Mortality in Mexico and Canada, 2014. AB - OBJECTIVES: The 2009-2010 influenza A (H1N1pdm09) pandemic caused substantial morbidity and mortality among young patients; however, mortality estimates have been confounded by regional differences in eligibility criteria and inclusion of selected populations. In 2013-2014, H1N1pdm09 became North America's dominant seasonal influenza strain. Our objective was to compare the baseline characteristics, resources, and treatments with outcomes among critically ill patients with influenza A (H1N1pdm09) in Mexican and Canadian hospitals in 2014 using consistent eligibility criteria. DESIGN: Observational study and a survey of available healthcare setting resources. SETTING: Twenty-one hospitals, 13 in Mexico and eight in Canada. PATIENTS: Critically ill patients with confirmed H1N1pdm09 during 2013-2014 influenza season. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome measures were 90-day mortality and independent predictors of mortality. Among 165 adult patients with H1N1pdm09-related critical illness between September 2013 and March 2014, mean age was 48.3 years, 64% were males, and nearly all influenza was community acquired. Patients were severely hypoxic (median PaO2-to-FIO2 ratio, 83 mm Hg), 97% received mechanical ventilation, with mean positive end-expiratory pressure of 14 cm H2O at the onset of critical illness and 26.7% received rescue oxygenation therapy with prone ventilation, extracorporeal life support, high-frequency oscillatory ventilation, or inhaled nitric oxide. At 90 days, mortality was 34.6% (13.9% in Canada vs 50.5% in Mexico, p < 0.0001). Independent predictors of mortality included lower presenting PaO2-to-FIO2 ratio (odds ratio, 0.89 per 10-point increase [95% CI, 0.80-0.99]), age (odds ratio, 1.49 per 10 yr increment [95% CI, 1.10-2.02]), and requiring critical care in Mexico (odds ratio, 7.76 [95% CI, 2.02-27.35]). ICUs in Canada generally had more beds, ventilators, healthcare personnel, and rescue oxygenation therapies. CONCLUSIONS: Influenza A (H1N1pdm09)-related critical illness still predominantly affects relatively young to middle-aged patients and is associated with severe hypoxemic respiratory failure. The local critical care system and available resources may be influential determinants of patient outcome. PMID- 27359088 TI - Simultaneous multisystem surgery: An important capability for the civilian trauma hospital. AB - Head injury commonly presents in association with torso or limb injuries, especially in blunt trauma mechanisms. Stopping life-threatening thoraco abdominal hemorrhage and preventing secondary brain injury are time critical priorities. Although simultaneous operative management by multiple teams has been common practice in the recent wars in Iraq and Afghanistan, simultaneous surgery is rare in most civilian settings. Nevertheless, situations arise whereby simultaneous craniotomy and chest or abdominal surgery is necessary to prevent mortality or reduce severe morbidity. We discuss two recent cases at our level one trauma centre, the challenges that surgeons and the operating room staff face and propose that with appropriate planning this surgical capability can be integrated into the systems of contemporary advanced trauma units. PMID- 27359089 TI - Audiological manifestations in mitochondrial encephalomyopathy lactic acidosis and stroke like episodes (MELAS) syndrome. AB - OBJECTIVES: Reports of audiological manifestations in specific subgroups of mitochondrial disorders are limited. This study aims to describe the audiological findings in patients with MELAS syndrome and m.3243A>G mutation. PATIENTS & METHODS: Audiological evaluation was carried out in eight patients with confirmed MELAS syndrome and m.3243A>G mutation. The evaluation included a complete neurological evaluation, pure tone audiometry (n=8), otoacoustic emissions (n=8) and brainstem evoked response audiometry (n=6), magnetic resonance imaging (n=8) and muscle biospy (n=6). RESULTS: Eight patients (Age range: 5-45 years; M:F-1:3) including six children and two adults underwent formal audiological evaluation. Five patients had hearing loss; of these two had "subclinical hearing loss", one had moderate and two had severe hearing loss. The abnormalities included abnormal audiometry (n=5), otoacoustic emission testing (n=7) and absent brainstem auditory evoked responses (n=1). The findings were suggestive of cochlear involvement in four and retrocochlear in one. CONCLUSIONS: This study shows that hearing loss of both cochlear and retrocochlear origin occurs in patients with MELAS and may be subclinical. Early referrals for audiological evaluation is warranted to recognize the subclinical hearing loss in these patients. The therapeutic implications include early interventions in the form of hearing aids, cochlear implants and cautioning the physicians for avoidance of aminoglycosides. PMID- 27359090 TI - Health term-born girls had higher levels of urine neutrophil gelatinase associated lipocalin than boys during the first postnatal days. AB - Neutrophil gelatinase-associated lipocalin (NGAL) is one of the most extensively examined biological markers for early prediction of acute kidney injury, but there is a lack of data on normal NGAL values in healthy term-born infants. This encouraged us to established serum and urine levels using samples collected from 38 girls and 50 boys, born at a median age of 39 weeks, during the first 48 hours after birth. CONCLUSION: Our findings showed that urine NGAL, but not serum levels, were significantly higher in girls than in boys. PMID- 27359091 TI - Children Exposed to Intimate Partner Violence: Conduct Problems, Interventions, and Partner Contact With the Child. AB - Children's contact with their mother's violent partner is a potentially important variable for understanding conduct problems among children exposed to intimate partner violence (IPV). Within the context of a treatment study evaluating a parenting intervention (Project Support) for families exiting a domestic violence shelter, this study tested four hypotheses regarding children's postshelter contact with their mother's violent partner: (1) participation in Project Support decreases the frequency of children's contact with their mother's violent partner; (2) postshelter contact is positively associated with children's conduct problems and is associated more strongly for girls than boys; (3) frequency of contact mediates Project Support's effects on children's conduct problems; and (4) frequency of contact is positively associated with IPV and partner-child aggression, and these latter associations help explain effects of contact on children's conduct problems. Participants were 66 women (26 White) with a child (32 girls) between 4 and 9 years. Families were assessed every 4 months for 20 months after departure from a domestic violence shelter. Project Support reduced the extent of partner-child contact. In addition, within-subject changes in contact over time were associated with girls', but not boys', conduct problems, and it partially mediated effects of Project Support on girls' conduct problems. Higher average levels of contact over time were also positively associated with further incidents of IPV and partner-child aggression, and partner-child aggression helped explain effects of contact on children's conduct problems. Children's postshelter contact with the mother's violent partner relates positively to several negative family outcomes. PMID- 27359094 TI - Response to Patryn and Zagaja. PMID- 27359095 TI - ADDENDUM: Technical standards and guidelines for spinal muscular atrophy testing. PMID- 27359096 TI - CORRIGENDUM: Phenotype-driven gene target definition in clinical genome-wide sequencing data interpretation. PMID- 27359097 TI - Cyanobacterial Polyhydroxybutyrate (PHB): Screening, Optimization and Characterization. AB - In modern life petroleum-based plastic has become indispensable due to its frequent use as an easily available and a low cost packaging and moulding material. However, its rapidly growing use is causing aquatic and terrestrial pollution. Under these circumstances, research and development for biodegradable plastic (bioplastics) is inevitable. Polyhydroxybutyrate (PHB), a type of microbial polyester that accumulates as a carbon/energy storage material in various microorganisms can be a good alternative. In this study, 23 cyanobacterial strains (15 heterocystous and 8 non-heterocystous) were screened for PHB production. The highest PHB (6.44% w/w of dry cells) was detected in Nostoc muscorum NCCU- 442 and the lowest in Spirulina platensis NCCU-S5 (0.51% w/w of dry cells), whereas no PHB was found in Cylindrospermum sp., Oscillatoria sp. and Plectonema sp. Presence of PHB granules in Nostoc muscorum NCCU- 442 was confirmed microscopically with Sudan black B and Nile red A staining. Pretreatment of biomass with methanol: acetone: water: dimethylformamide [40: 40: 18: 2 (MAD-I)] with 2 h magnetic bar stirring followed by 30 h continuous chloroform soxhlet extraction acted as optimal extraction conditions. Optimized physicochemical conditions viz. 7.5 pH, 30 degrees C temperature, 10:14 h light:dark periods with 0.4% glucose (as additional carbon source), 1.0 gl-1 sodium chloride and phosphorus deficiency yielded 26.37% PHB on 7th day instead of 21st day. Using FTIR, 1H NMR and GC-MS, extracted polymer was identified as PHB. Thermal properties (melting temperature, decomposition temperatures etc.) of the extracted polymer were determined by TGA and DSC. Further, the polymer showed good tensile strength and young's modulus with a low extension to break ratio comparable to petrochemical plastic. Biodegradability potential tested as weight loss percentage showed efficient degradation (24.58%) of PHB within 60 days by mixed microbial culture in comparison to petrochemical plastic. PMID- 27359098 TI - Measurements of cesium in Arctic beluga and caribou before and after the Fukushima accident of 2011. AB - Concern from northern communities following the Fukushima Daiichi nuclear accident of March 2011 has prompted a reassessment of the safety of their traditional foods with respect to radioactivity levels. To this end, a study was conducted to measure the levels of radionuclides in Arctic caribou (Rangifer tarandus) and beluga (Delphinapterus leucas). The main radionuclide of concern is cesium-137, which is easily transferred through the lichen-caribou food chain. Previous studies have been conducted on the cesium-137 levels in Canadian caribou herds from 1958 to 2000, allowing researchers to determine the amount of cesium 137 in caribou specifically attributable to atmospheric weapons testing and the Chernobyl nuclear accident in 1986. In this study, samples of lichens, mushrooms, caribou, beluga and beluga prey collected before and after the Fukushima accident were analyzed for radioactivity levels. Samples were processed and measured using gamma ray spectroscopy to identify the radionuclides present and determine the radioactivity concentration. Both calibration standards and Monte Carlo simulations were used to determine the efficiency of the detectors for the samples, taking into account differences in individual sample sizes as well as matrices. In particular, a careful analysis of the atomic composition of lichens and mushrooms was performed to ensure the efficiencies for these sample types were correct. A comparison of the concentrations from before and after the accident indicated that there was no increase in radioactivity as a result of the atmospheric plume from the Fukushima accident. Some cesium-137, likely attributable to fallout from atmospheric weapons testing of the 1950s and 1960s (since there was no cesium-134 measured in the samples), was measured in the post Fukushima caribou and beluga whale samples; however, this amount was determined to be insignificant for any radiological concern (9.1 +/- 1.8 and 0.63 +/- 0.23 Bq kg-1 ww respectively). The activity concentrations of cesium-137 was about 200 times smaller than that of natural radioactive potassium in the beluga samples. Both the caribou and beluga results showed that these foods continue to be a healthy food choice for northern Canadians with respect to radioactivity, and this result has been communicated to the nearby northern communities and stakeholders. PMID- 27359099 TI - Chronic Contractile Dysfunction without Hypertrophy Does Not Provoke a Compensatory Transcriptional Response in Mouse Hearts. AB - Diseased myocardium from humans and experimental animal models shows heightened expression and activity of a specific subtype of phospholipase C (PLC), the splice variant PLCbeta1b. Previous studies from our group showed that increasing PLCbeta1b expression in adult mouse hearts by viral transduction was sufficient to cause sustained contractile dysfunction of rapid onset, which was maintained indefinitely in the absence of other pathological changes in the myocardium. We hypothesized that impaired contractility alone would be sufficient to induce a compensatory transcriptional response. Unbiased, comprehensive mRNA-sequencing was performed on 6 biological replicates of rAAV6-treated blank, PLCbeta1b and PLCbeta1a (closely related but inactive splice variant) hearts 8 weeks after injection, when reduced contractility was manifest in PLCbeta1b hearts without evidence of induced hypertrophy. Expression of PLCbeta1b resulted in expression changes in only 9 genes at FDR<0.1 when compared with control and these genes appeared unrelated to contractility. Importantly, PLCbeta1a caused similar mild expression changes to PLCbeta1b, despite a complete lack of effect of this isoform on cardiac contractility. We conclude that contractile depression caused by PLCbeta1b activation is largely independent of changes in the transcriptome, and thus that lowered contractility is not sufficient in itself to provoke measurable transcriptomic alterations. In addition, our data stress the importance of a stringent control group to filter out transcriptional changes unrelated to cardiac function. PMID- 27359100 TI - Nursing team leader handover in the intensive care unit contains diverse and inconsistent content: An observational study. AB - BACKGROUND: Despite a proliferation of evidence and the development of standardised tools to improve communication at handover, evidence to guide the handover of critical patient information between nursing team leaders in the intensive care unit is limited. OBJECTIVE: The study aim was to determine the content of information handed over during intensive care nursing team leader shift-to-shift handover. DESIGN: A prospective observational study. SETTING: A 21 bed medical/surgical adult intensive care unit specialising in cardiothoracic surgery at a tertiary referral hospital in Queensland, Australia. PARTICIPANTS: Senior nurses (Grade 5 and 6 Registered nurses) working in team leader roles, employed in the intensive care unit were sampled. METHOD: After obtaining consent from nursing staff, team leader handovers were audiotaped over 20 days. Audio recordings were transcribed and analysed using deductive and inductive content analysis. The frequency of content discussed at handover that fell within the a priori categories of the ISBAR schema (Identify-Situation-Background-Assessment Recommendation) was calculated. RESULTS: Forty nursing team leader handovers were recorded resulting in 277 patient handovers and a median of 7 (IQR 2) patients discussed at each handover. The majority of nurses discussed the Identity (99%), Situation (96%) and Background (88%) of the patient, however Assessment (69%) content was varied and patient Recommendations (60%) were discussed less frequently. A diverse range of additional information was discussed that did not fit into the ISBAR schema. CONCLUSIONS: Despite universal acknowledgement of the importance of nursing team leader handover, there are no previous studies assessing its content. Study findings indicate that nursing team leader handovers contain diverse and inconsistent content, which could lead to inadequate handovers that compromise patient safety. Further work is required to develop structured handover processes for nursing team leader handovers. PMID- 27359101 TI - Wild-Caught and Farm-Reared Amphibians are Important Reservoirs of Salmonella, A Study in North-East Thailand. AB - The role of amphibians as Salmonella reservoirs has not been as well studied as in reptiles, where the literature is abundant. Recent outbreaks of salmonellosis associated with exotic pet frogs have occurred in United States. Frog farming and wild frog harvesting have increased the international trade in these species. This necessitates a better understanding of the risk of salmonellosis transmission from amphibians to humans. We explored the presence of Salmonella in amphibians (frogs and toads) in Thailand, where farmed and wild frogs as well as toads are present. These live animals are easily found in the local markets and are used as food. Exportation of frog meat from Thailand is common. During March June 2014, ninety-seven frogs were collected from several habitats, including frog farms, urban areas and protected natural areas. The collected amphibians were tested for the presence of Salmonella. The overall prevalence of Salmonella was 69.07% (90.00% in farm animals, 0% in urban area animals and 44.83% in protected area animals). Eight serovars of Salmonella were isolated: subsp. diarizonae ser. 50:k:z, Hvittingfoss, Muenchen, Newport, Stanley, Thompson, Panama and Wandsworth. Six of the identified serovars, Hvittingfoss, Newport, Panama, Stanley, Thompson and Wandsworth, have been detected in humans in Thailand. According to our results, amphibians are reservoirs of Salmonella and can be a public health concern when used as a source of protein for humans. PMID- 27359103 TI - Time-Resolved Infrared (TRIR) Studies of Oxycarbonylnitrenes. AB - N-Ethyloxycarbonyl-S,S-dibenzothiphene sulfilimine and N-t-butyloxycarbonyl-S,S dibenzothiphene sulfilimine have been utilized as precursors to ethoxycarbonylnitrene and t-butyloxycarbonylnitrene. B3LYP/6-31G(d) calculations predict triplet ground states for both oxycarbonylnitrenes, albeit by small margins. Triplet ethoxycarbonylnitrene and triplet t-butyloxycarbonylnitrene have been observed following photolysis of these sulfilimine precursors by time resolved infrared (TRIR) spectroscopy. Kinetic studies show that ethoxycarbonylnitrene reacts with solvents such as acetonitrile and cyclohexane, while t-butyloxycarbonylnitrene undergoes an intramolecular insertion reaction to produce 5,5-dimethyl oxazolidinone. Product analysis following photolysis of N-t butyloxycarbonyl-S,S-dibenzothiphene sulfilimine confirms that the oxazolidinone is the major product with an estimated yield of 90%. The products from these two nitrenes are derived from the corresponding singlet nitrene, either directly or via thermal repopulation of the singlet from the lower-energy triplet nitrene. PMID- 27359102 TI - Conservation in Mammals of Genes Associated with Aggression-Related Behavioral Phenotypes in Honey Bees. AB - The emerging field of sociogenomics explores the relations between social behavior and genome structure and function. An important question is the extent to which associations between social behavior and gene expression are conserved among the Metazoa. Prior experimental work in an invertebrate model of social behavior, the honey bee, revealed distinct brain gene expression patterns in African and European honey bees, and within European honey bees with different behavioral phenotypes. The present work is a computational study of these previous findings in which we analyze, by orthology determination, the extent to which genes that are socially regulated in honey bees are conserved across the Metazoa. We found that the differentially expressed gene sets associated with alarm pheromone response, the difference between old and young bees, and the colony influence on soldier bees, are enriched in widely conserved genes, indicating that these differences have genomic bases shared with many other metazoans. By contrast, the sets of differentially expressed genes associated with the differences between African and European forager and guard bees are depleted in widely conserved genes, indicating that the genomic basis for this social behavior is relatively specific to honey bees. For the alarm pheromone response gene set, we found a particularly high degree of conservation with mammals, even though the alarm pheromone itself is bee-specific. Gene Ontology identification of human orthologs to the strongly conserved honey bee genes associated with the alarm pheromone response shows overrepresentation of protein metabolism, regulation of protein complex formation, and protein folding, perhaps associated with remodeling of critical neural circuits in response to alarm pheromone. We hypothesize that such remodeling may be an adaptation of social animals to process and respond appropriately to the complex patterns of conspecific communication essential for social organization. PMID- 27359104 TI - From cradle to grave via the dissection room: the role of foetal and infant bodies in anatomical education from the late 1700s to early 1900s. AB - The preponderance of men in the narrative of anatomical education during the 1800s has skewed the historical perception of medical cadavers in favour of adult men, and stifled the conversation about the less portrayed individuals, especially children. Although underrepresented in both the historical literature and skeletal remains from archaeological contexts dated to the 1800s, these sources nevertheless illustrate that foetal and infant cadavers were a prized source of knowledge. In the late 1700s and 1800s foetal and infant cadavers were acquired by anatomists following body snatching from graveyards, from the child's death in a charitable hospital, death from infectious disease in large poor families, or following infanticide by desperate unwed mothers. Study of foetal and infant remains from the 1800s in the anatomical collection at the University of Cambridge shows that their bodies were treated differently to adults by anatomists. In contrast to adults it was extremely rare for foetal and infant cadavers to undergo craniotomy, and thoracotomy seems to have been performed through costal cartilages of the chest rather than the ribs themselves. However, many infants and foetuses do show evidence for knife marks on the cranium indicating surgical removal of the scalp by anatomists. These bodies were much more likely to be curated long term in anatomical collections and museums than were adult males who had undergone dissection. They were prized both for demonstrating normal anatomical development, but also congenital abnormalities that led to an early death. The current findings show that the dissection of foetal and infant cadavers was more widespread than previous research on anatomical education suggests. This research details the important role of the youngest members of society in anatomical education during the long 19th century, and how the social identity of individuals in this subgroup affected their acquisition, treatment and disposal by elite medical men of the time. PMID- 27359105 TI - BST2 Mediates Osteoblast Differentiation via the BMP2 Signaling Pathway in Human Alveolar-Derived Bone Marrow Stromal Cells. AB - The molecular mechanisms controlling the differentiation of bone marrow stromal stem cells into osteoblasts remain largely unknown. In this study, we investigated whether bone marrow stromal antigen 2 (BST2) influences differentiation toward the osteoblasts lineage. BST2 mRNA expression in human alveolar-derived bone marrow stromal cells (hAD-BMSCs) increased during differentiation into osteoblasts. hAD-BMSCs differentiation into osteoblasts and the mRNA expression of the bone-specific markers alkaline phosphatase, collagen type alpha 1, bone sialoprotein, osteocalcin, and osterix were reduced by BST2 knockdown using siRNA. Furthermore, BST2 knockdown in hAD-BMSCs resulted in decreased RUNX2 mRNA and protein expression. We hypothesized that BST2 is involved in differentiation of into osteoblasts via the BMP2 signaling pathway. Accordingly, we evaluated the mRNA expression levels of BMP2, BMP receptors (BMPR1 and 2), and the downstream signaling molecules SMAD1, SMAD4, and p SMAD1/5/8 in BST2 knockdown cells. BMP2 expression following the induction of differentiation was significantly lower in BST2 knockdown cells than in cells treated with a non-targeting control siRNA. Similar results were found for the knockdown of the BMP2 receptor- BMPR1A. We also identified significantly lower expression of SMAD1, SMAD4, and p-SMAD1/5/8 in the BST2 knockdown cells than control cells. Our data provide the first evidence that BST2 is involved in the osteogenic differentiation of bone marrow stromal cells via the regulation of the BMP2 signaling pathway. PMID- 27359107 TI - Zinc Isotope Fractionation in the Hyperaccumulator Noccaea caerulescens and the Nonaccumulating Plant Thlaspi arvense at Low and High Zn Supply. AB - On the basis of our previous field survey, we postulate that the pattern and degree of zinc (Zn) isotope fractionation in the Zn hyperaccumulator Noccaea caerulescens (J. & C. Presl) F. K. Mey may reflect a relationship between Zn bioavailability and plant uptake strategies. Here, we investigated Zn isotope discrimination during Zn uptake and translocation in N. caerulescens and in a nonaccumulator Thlaspi arvense L. with a contrasting Zn accumulation ability in response to low (Zn-L) and high (Zn-H) Zn supplies. The average isotope fractionations of the N. caerulescens plant as a whole, relative to solution (Delta(66)Znplant-solution), were -0.06 and -0.120/00 at Zn-L-C and Zn-H-C, respectively, indicative of the predominance of a high-affinity (e.g., ZIP transporter proteins) transport across the root cell membrane. For T. arvense, plants were more enriched in light isotopes under Zn-H-A (Delta(66)Znplant solution = -0.260/00) than under Zn-L-A and N. caerulescens plants, implying that a low-affinity (e.g., ion channel) transport might begin to function in the nonaccumulating plants when external Zn supply increases. Within the root tissues of both species, the apoplast fractions retained up to 30% of Zn mass under Zn-H. Moreover, the highest delta(66)Zn (0.750/00-0.860/00) was found in tightly bound apoplastic Zn, pointing to the strong sequestration in roots (e.g., binding to high-affinity ligands/precipitation with phosphate) when plants suffer from high Zn stress. During translocation, the magnitude of isotope fractionation was significantly greater at Zn-H (Delta(66)Znroot-shoot = 0.790/00) than at Zn-L, indicating that fractionation mechanisms associated with root-shoot translocation might be identical to the two plant species. Hence, we clearly demonstrated that Zn isotope fractionation could provide insight into the internal sequestration mechanisms of roots when plants respond to low and high Zn supplies. PMID- 27359108 TI - Insights into the Formation and Structures of Molecular Gels by Diimidazolium Salt Gelators in Ionic Liquids or "Normal" Solvents. AB - Insights are provided into the properties of molecular gels formed by diimidazolium salts both in "normal" solvents and ionic liquids. These materials can be interesting for applications in green and sustainable chemistry in which ionic liquids play a significant role, like catalysis and energy. In particular, two positional isomers of a diimidazolium cation have been examined with a wide range of anions for their ability to form gel phases. In particular, di-, tri-, and tetravalent anions bearing aliphatic or aromatic spacers were paired with the divalent cations. The properties of the organo- and ionogels formed have been analyzed by means of several different techniques, including calorimetry, rheology, resonance light scattering, UV/Vis absorption, polarizing optical microscopy, and powder X-ray diffraction measurements. The investigations performed enabled us to obtain a wide range of conductive materials characterized by a high thermal stability and a low corrosiveness of the gelator (organogels) or of both gelator and solvent (ionogels). The information gained should be useful in the broader quest to identify and promote their applications. PMID- 27359106 TI - Examining health literacy among urban African-American adolescents with asthma. AB - OBJECTIVE: This exploratory study assessed health literacy among urban African American high school students to improve understanding of the association between adolescent health literacy and asthma. METHODS: We conducted a secondary data analysis of the control group (n = 181) of the Puff City randomized controlled trial (2006-2010), a web-based intervention to promote asthma management among students, grades 9 through 12. A validated self-report 3-item health literacy screening instrument was completed at final online follow-up survey. Logistic regression was used to explore the association between health literacy, demographic characteristics, quality of life, asthma management, and health care utilization. RESULTS: Multivariate analysis revealed that an overall inadequate health literacy score was associated with students who were more likely to be younger (OR 0.61; 95% CI 0.44-0.84), not on Medicaid (OR 0.36; 95% CI 0.17-0.76), have at least one hospitalization (OR 1.29; 95% CI 1.07-1.56); and a lower overall quality of life (OR 0.75; 95% CI 0.59-0.95). Those lacking confidence in filling out medical forms, needing help reading hospital materials, and having difficulty understanding written information were more likely to not have a rescue inhaler (OR 0.49; 95% CI 0.25-0.94), have one or more emergency visits (OR 1.21 95% CI 1.02-1.43), and one or more hospitalizations (OR 1.19; 95% CI 1.01 1.41), respectively. CONCLUSIONS: The findings indicate a significant association between inadequate health literary and suboptimal asthma management. It is important to advance understanding of adolescent health literacy, especially those at-risk, as they assume asthma self-management tasks and move toward independent adult self-care. PMID- 27359109 TI - Targeting transradial approach: an updated systematic review and meta-analysis. AB - INTRODUCTION: Transradial access (TRA) emerged in the last two decades as a valid alternative to the standard transfemoral access (TFA) for cardiac catheterization and percutaneous coronary intervention (PCI). Due to contrasting results, the penetration and uptake of TRA in real-world clinical practice has been slow and still limited to high experienced center. EVIDENCE ACQUISITION: We performed an updated systematic review and study-level meta-analysis of randomized controlled trials (RCTs) that investigated the efficacy and safety of TRA versus TFA for PCI in patients with ACS. MEDLINE, Scopus, the Cochrane Library, and TCTMD.org were searched for abstracts, manuscripts, and conference reports published until April 31, 2016. The three pre-specified primary endpoints of interest were: all-cause mortality, major bleeding and major adverse cardiac events (MACE), at 30 days of follow-up. Primary analytic approach was according the intention-to-treat principle using inverse variance weighted random effect models. EVIDENCE SYNTHESIS: Study level data from 12 RCTs were extracted and analyzed. TRA compared with TFA in ACS patients undergoing invasive management was associated with a significant reduction in the risk of mortality (RR=0.72; 95% CI: 0.59 0.88; P=0.002), major bleeding (RR 0.48; 95% CI: 0.37-0.61; P<0.00001) and MACE (RR 0.81; 95% CI: 0.69-0.96; P=0.01), with similar procedural rate of success. In addition, TRA was associated with reduced in-hospital length of stay. There were no differences in the risk of stroke, myocardial infarction and target vessel or target lesion revascularization. CONCLUSIONS: The results of the present study confirm TRA as the preferred routine upfront strategy for ACS patients undergoing PCI. PMID- 27359110 TI - Pharmacokinetics study of Zr-89-labeled melanin nanoparticle in iron-overload mice. AB - Melanin, a natural biological pigment present in many organisms, has been found to exhibit multiple functions. An important property of melanin is its ability to chelate metal ions strongly, which might be developed as an iron chelator for iron overload therapy. Herein, we prepared the ultrasmall water-soluble melanin nanoparticle (MP) and firstly evaluate the pharmacokinetics of MP in iron overload mice to provide scientific basis for treating iron-overload. To study the circulation time and biodistribution, MP was labeled with (89)Zr, a long half life (78.4h) positron-emitting metal which is suited for the labeling of nanoparticles and large bioactive molecule. MP was chelated with (89)Zr directly at pH5, resulting in non-decay-corrected yield of 89.6% and a radiochemical purity of more than 98%. The specific activity was at least190 MBq/MUmol. The (89)Zr-MP was stable in human plasma and PBS for at least 48h. The half-life of (89)Zr-MP was about 15.70+/-1.74h in iron-overload mice. Biodistribution studies and MicroPET imaging showed that (89)Zr-MP mainly accumulated in liver and spleen, which are the target organ of iron-overload. The results indicate that the melanin nanoparticle is promising for further iron overload therapy. PMID- 27359111 TI - Sequence conservation predicts T cell reactivity against ragweed allergens. AB - BACKGROUND: Ragweed is a major cause of seasonal allergy, affecting millions of people worldwide. Several allergens have been defined based on IgE reactivity, but their relative immunogenicity in terms of T cell responses has not been studied. OBJECTIVE: We comprehensively characterized T cell responses from atopic, ragweed-allergic subjects to Amb a 1, Amb a 3, Amb a 4, Amb a 5, Amb a 6, Amb a 8, Amb a 9, Amb a 10, Amb a 11, and Amb p 5 and examined their correlation with serological reactivity and sequence conservation in other allergens. METHODS: Peripheral blood mononuclear cells (PBMCs) from donors positive for IgE towards ragweed extracts after in vitro expansion for secretion of IL-5 (a representative Th2 cytokine) and IFN-gamma (Th1) in response to a panel of overlapping peptides spanning the above-listed allergens were assessed. RESULTS: Three previously identified dominant T cell epitopes (Amb a 1 176-191, 200-215, and 344-359) were confirmed, and three novel dominant epitopes (Amb a 1 280-295, 304-319, and 320-335) were identified. Amb a 1, the dominant IgE allergen, was also the dominant T cell allergen, but dominance patterns for T cell and IgE responses for the other ragweed allergens did not correlate. Dominance for T cell responses correlated with conservation of ragweed epitopes with sequences of other well-known allergens. CONCLUSIONS AND CLINICAL RELEVANCE: These results provide the first assessment of the hierarchy of T cell reactivity in ragweed allergens, which is distinct from that observed for IgE reactivity and influenced by T cell epitope sequence conservation. The results suggest that ragweed allergens associated with lesser IgE reactivity and significant T cell reactivity may be targeted for T cell immunotherapy, and further support the development of immunotherapies against epitopes conserved across species to generate broad reactivity against many common allergens. PMID- 27359112 TI - Prenatal exposures and DNA methylation in newborns: a pilot study in Durban, South Africa. AB - The in utero environment has the potential to influence epigenetic programming and subsequently the health of offspring. Even though pregnant women living in urban Africa are exposed to multiple chemicals and infectious agents that may impact their developing children, the neonatal epigenome has not been studied in these regions. We assessed whether prenatal exposures to air pollution and maternal human immunodeficiency virus (HIV) are associated with changes to DNA methylation throughout the epigenome using a pilot sample from the Mother and Child Environmental (MACE) birth cohort, of which 36% of the mothers are HIV positive. Families living in a high air pollution region (south Durban, n = 11) and a low air pollution region (north Durban, n = 11) with comparable socioeconomic characteristics were selected for analysis. DNA methylation was quantified in cord blood plasma DNA at >430 000 CpG sites using the Infinium HumanMethylation450 BeadChip. Sites associated with living in south Durban or maternal HIV infection (p < 0.001) were more likely to be hypomethylated and located in CpG islands. Top differentially methylated sites by region of Durban were enriched in pathways related to xenobiotic metabolism, oxygen and gas transport, and sensory perception of chemical stimuli when performing gene set enrichment testing with LRpath. Differentially methylated sites by maternal HIV status were enriched in cytochrome P450s, pathways involved in detection of chemical stimuli, metabolic processes, and viral regulation and processing. Given the small sample size of the study, future work examining the impact of prenatal exposures to air pollution, maternal infection, and antiviral treatment on the epigenome and downstream health implications is merited in Sub-Saharan African populations. PMID- 27359113 TI - A Platform for Rapid, Quantitative Assessment of Multiple Drug Combinations Simultaneously in Solid Tumors In Vivo. AB - While advances in high-throughput screening have resulted in increased ability to identify synergistic anti-cancer drug combinations, validation of drug synergy in the in vivo setting and prioritization of combinations for clinical development remain low-throughput and resource intensive. Furthermore, there is currently no viable method for prospectively assessing drug synergy directly in human patients in order to potentially tailor therapies. To address these issues we have employed the previously described CIVO platform and developed a quantitative approach for investigating multiple combination hypotheses simultaneously in single living tumors. This platform provides a rapid, quantitative and cost effective approach to compare and prioritize drug combinations based on evidence of synergistic tumor cell killing in the live tumor context. Using a gemcitabine resistant model of pancreatic cancer, we efficiently investigated nine rationally selected Abraxane-based combinations employing only 19 xenografted mice. Among the drugs tested, the BCL2/BCLxL inhibitor ABT-263 was identified as the one agent that synergized with Abraxane(r) to enhance acute induction of localized apoptosis in this model of human pancreatic cancer. Importantly, results obtained with CIVO accurately predicted the outcome of systemic dosing studies in the same model where superior tumor regression induced by the Abraxane/ABT-263 combination was observed compared to that induced by either single agent. This supports expanded use of CIVO as an in vivo platform for expedited in vivo drug combination validation and sets the stage for performing toxicity-sparing drug combination studies directly in cancer patients with solid malignancies. PMID- 27359115 TI - Endograft Sizing for Endovascular Aortic Repair and Incidence of Endoleak Type 1A. AB - OBJECTIVE: In endovascular aortic aneurysm repair (EVAR), proximal type 1A endoleaks can occur as a result of hostile neck anatomy or over- or undersizing of the endograft. As the current standard is based on the diameter or average of the short and long axes in a central lumen reconstruction image, it can falter in irregularly shaped aortic necks. An alternative method is circumference-based, therefore minimizing the measurement error. In this study we aimed to assess the degree of discrepancy between both methods and the association of this discrepancy with the occurrence of endoleak type 1A. METHODS: All patients with early (<30 days post-operative) endoleak type 1A after elective EVAR at our center between 2004 and 2016 were identified for a retrospective case-control study. Control patients were matched based on hostile neck anatomy, such as calcification, thrombus, reverse taper, and beta-angulation. The aortic neck diameter was measured using the traditional, diameter-based method as well as an alternative method, based on the circumference of the aortic neck. RESULTS: In 482 EVAR patients, 18 early endoleak type 1A cases were found (3.9%). After exclusion, 12 cases remained and 48 matching controls were found. No significant differences were found between the two measuring methods at any level below the renal arteries. The inter-observer variability was significant for the D(mean) (0.4 +/- 1.69 mm, P = .02) and was larger than the D(circ) method (-0.1 +/- 1.03 mm, P = .35). In only four out of 12 cases the endograft size was 10-20% larger than the D(mean) and D(circ) measurements. The differences between the diameter of the D(mean) and D(circ) and the chosen endograft were smaller for the case group (-8 +/- 25.6% and -7 +/- 24%) than for the control group. (-12.4 +/- 12.4% and -11 +/- 10.7%). CONCLUSION: The difference between the D(mean) and D(circ) methods for aortic neck measurement was not large enough to play a significant role in the incidence of endoleak type 1A. Inadequate oversizing and considerable beta-angulation of the aortic neck may have been the cause of endoleak type 1A in this population. Robust and well-investigated sizing methods are paramount for accurate endograft sizing and prevention of endoleak type 1A. Therefore the lack of studies in this field and a sizeable inter-observer variability do not justify the widespread reliance on the traditional diameter-based methods for endograft sizing. PMID- 27359116 TI - Spatial Representativeness of Environmental DNA Metabarcoding Signal for Fish Biodiversity Assessment in a Natural Freshwater System. AB - In the last few years, the study of environmental DNA (eDNA) has drawn attention for many reasons, including its advantages for monitoring and conservation purposes. So far, in aquatic environments, most of eDNA research has focused on the detection of single species using species-specific markers. Recently, species inventories based on the analysis of a single generalist marker targeting a larger taxonomic group (eDNA metabarcoding) have proven useful for bony fish and amphibian biodiversity surveys. This approach involves in situ filtering of large volumes of water followed by amplification and sequencing of a short discriminative fragment from the 12S rDNA mitochondrial gene. In this study, we went one step further by investigating the spatial representativeness (i.e. ecological reliability and signal variability in space) of eDNA metabarcoding for large-scale fish biodiversity assessment in a freshwater system including lentic and lotic environments. We tested the ability of this approach to characterize large-scale organization of fish communities along a longitudinal gradient, from a lake to the outflowing river. First, our results confirm that eDNA metabarcoding is more efficient than a single traditional sampling campaign to detect species presence, especially in rivers. Second, the species list obtained using this approach is comparable to the one obtained when cumulating all traditional sampling sessions since 1995 and 1988 for the lake and the river, respectively. In conclusion, eDNA metabarcoding gives a faithful description of local fish biodiversity in the study system, more specifically within a range of a few kilometers along the river in our study conditions, i.e. longer than a traditional fish sampling site. PMID- 27359114 TI - The Transient Receptor Potential (TRP) Channel Family in Colletotrichum graminicola: A Molecular and Physiological Analysis. AB - Calcium (Ca2+) is a universal second messenger in all higher organisms and centrally involved in the launch of responses to environmental stimuli. Ca2+ signals in the cytosol are initiated by the activation of Ca2+ channels in the plasma membrane and/or in endomembranes. Yeast (Saccharomyces cerevisiae) contains a Ca2+-permeable channel of the TRP family, TRPY1, which is localized in the vacuolar membrane and contributes to cytosolic free Ca2+ ([Ca2+]cyt) elevations, for example in response to osmotic upshock. A TRPY1 homologue in the rice blast fungus is known to be important for growth and pathogenicity. To determine the role of the TRP channel family in the maize pathogen Colletotrichum graminicola, proteins homologous to TRPY1 were searched. This identified not one, but four genes in the C. graminicola genome, which had putative orthologs in other fungi, and which we named CgTRPF1 through 4. The topology of the CgTRPF proteins resembled that of TRPY1, albeit with a variable number of transmembrane (TM) domains additional to the six-TM-domain core and a diverse arrangement of putatively Ca2+-binding acidic motifs. All CgTRPF genes were expressed in axenic culture and throughout the infection of maize. Like TRPY1, all TRPF proteins of C. graminicola were localized intracellularly, albeit three of them were found not in large vacuoles, but co-localized in vesicular structures. Deletion strains for the CgTRPF genes were not altered in processes thought to involve Ca2+ release from internal stores, i.e. spore germination, the utilization of complex carbon sources, and the generation of tip-focussed [Ca2+]cyt spikes. Heterologous expression of CgTRPF1 through 4 in a tryp1Delta yeast mutant revealed that none of the channels mediated the release of Ca2+ in response to osmotic upshock. Accordingly, aequorin-based [Ca2+]cyt measurements of C. graminicola showed that in this fungus, osmotic upshock-triggered [Ca2+]cyt elevations were generated entirely by influx of Ca2+ from the extracellular space. Cgtrpf mutants did not show pathogenicity defects in leaf infection assays. In summary, our study reveals major differences between different fungi in the contribution of TRP channels to Ca2+-mediated signal transduction. PMID- 27359117 TI - Prognostic Value of ADAMTS Proteases and Their Substrates in Epithelial Ovarian Cancer. AB - BACKGROUND: ADAMTS are metalloproteases with disintegrin and thrombospondin motifs. They are secreted proteases playing a role in biological processes such as inflammation, angiogenesis, and urogenital development. ADAMTS have specific substrates, such as the proteoglycans (PG) versican, aggrecan, and brevican. Despite data indicating a role of ADAMTS in tumor invasion and metastases, effects played by these molecules in cancer progression are still controversial. In ovarian cancer, the importance of ADAMTS gene mutations was recently described and related to chemotherapy outcome. OBJECTIVE: To analyze protein levels of ADAMTS-1, -4, and -5, and TIMP-3 in human ovarian cancer classified as benign, borderline, or malignant. We also assessed the expression of the ADAMTS substrates aggrecan, brevican, and versican in these neoplasms. Correlations between overall survival and protein expression were performed. METHODS: Tumors were classified according to the WHO Classification of Tumors of Female Reproductive Organs. Protein and PG expression was studied by immunohistochemistry. Differences in labeling were analyzed by percent measurements of stained areas. RESULTS: ADAMTS-1, ADAMTS-5, and its tissue inhibitor TIMP-3 are increased in borderline and malignant tumors compared to benign neoplasms. Aggrecan and versican levels were increased in malignant subtypes compared to benign ovarian cancer. Higher ADAMTS-1, TIMP-3, and versican expression was associated with a shorter overall survival. CONCLUSIONS: Comparison of protease, TIMP-3, and substrate expression showed that in malignant tumors all ADAMTS and TIMP-3 expression levels were significantly raised compared to the substrates studied. PMID- 27359121 TI - 2015 Outstanding Manuscript Awards. AB - Congratulations to the winners of the 2015 Outstanding Manuscript Awards, as determined by the Editorial Board and the Editors of the Journal of Athletic Training. PMID- 27359118 TI - Effects of a Dicalcium and Tetracalcium Phosphate-Based Desensitizer on In Vitro Dentin Permeability. AB - The present study evaluated the effectiveness of a dicalcium and tetracalcium phosphate-based desensitizer in reducing dentin permeability in vitro. Dentin fluid flow was measured before and after treatment of dentin with patent dentinal tubules using 1 or 3 applications of the dicalcium and tetracalcium phosphate containing agent TeethmateTM (TM) and comparing the results with two sodium fluoride varnishes VellaTM (VLA) and VanishTM (VAN), after storage in artificial saliva for 24 h, 48 h and 7 days. Significant differences were observed among the 4 methods employed for reducing dentin permeability (p < 0.001) and the 3 post treatment times (p < 0.001). VLA and VAN never achieved 50% permeability reductions consistently in any of the 3 time periods. Only the calcium phosphate based desensitizer applied for 3 times consistently reduced dentin permeability by 50% after 24 h. When applied once, the permeability reduction of TM increased progressively over the 3 time periods. After 7 days, only one and three applications of the calcium phosphate-based desensitizer consistently reduced dentin permeability by more than 50%. Permeability reductions corresponded well with scanning electron microscopy examination of dentinal tubule orifice occlusion in dentin specimens treated with the agents. Overall, the dicalcium and tetracalcium phosphate-based desensitizer is effective in reducing dentin permeability via a tubule occlusion mechanism. The ability of the agent to reduce dentin permeability renders it to be potentially useful as a clinical dentin desensitizing agent, which has to be confirmed in future clinical studies. By contrast, the two sodium fluoride varnishes are not effective in dentin permeability reduction and should be considered as topical fluoride delivering agents rather than tubular orifice-blocking agents. PMID- 27359123 TI - Fluorescent PEGulated Oligourethane Nanoparticles for Long-Term Cellular Tracing. AB - We have introduced a new ABA-type amphiphilic block copolymer consisting of functional oligourethane hydrophobic blocks and two polyethylene glycol (PEG) hydrophilic blocks. The polymer was synthesized in a single step by step-growth polymerization between two monomers, namely tetraphenylethylene (TPE)-diol and hexamehylene di-isocyanate in the presence of a monofunctional impurity PEG-2000. The polymer exhibits facile self-assembly in water by synergistic effects of H bonding and pi-pi interaction among the oligourethane core, leading to the formation of robust nanoparticles with remarkable aggregation-induced emission (AIE). These nanoparticles show very low critical aggregation concentration, stability over a large pH window, and excellent biocompatibility as revealed by an MTT assay. Cellular imaging with cancer cells showed facile cellular uptake and, more importantly, retention of AIE in cellular milieu for long times, which was successfully utilized for long-term cancer cell tracking. PMID- 27359122 TI - Genome-Wide Association Study of Meat Quality Traits in Nellore Cattle. AB - The objective of this study was to identify genomic regions that are associated with meat quality traits in the Nellore breed. Nellore steers were finished in feedlots and slaughtered at a commercial slaughterhouse. This analysis included 1,822 phenotypic records of tenderness and 1,873 marbling records. After quality control, 1,630 animals genotyped for tenderness, 1,633 animals genotyped for marbling, and 369,722 SNPs remained. The results are reported as the proportion of variance explained by windows of 150 adjacent SNPs. Only windows with largest effects were considered. The genomic regions were located on chromosomes 5, 15, 16 and 25 for marbling and on chromosomes 5, 7, 10, 14 and 21 for tenderness. These windows explained 3,89% and 3,80% of the additive genetic variance for marbling and tenderness, respectively. The genes associated with the traits are related to growth, muscle development and lipid metabolism. The study of these genes in Nellore cattle is the first step in the identification of causal mutations that will contribute to the genetic evaluation of the breed. PMID- 27359125 TI - Amelogenesis Imperfecta and Early Restorative Crown Therapy: An Interview Study with Adolescents and Young Adults on Their Experiences. AB - Patients with Amelogenesis imperfecta (AI) can present with rapid tooth loss or fractures of enamel as well as alterations in enamel thickness, color, and shape; factors that may compromise aesthetic appearance and masticatory function. The aim was to explore the experiences and perceptions of adolescents and young adults living with AI and receiving early prosthetic therapy. Seven patients with severe AI aged 16 to 23 years who underwent porcelain crown therapy participated in one-to-one individual interviews. The interviews followed a topic guide consisting of open-ended questions related to experiences of having AI. Transcripts from the interviews were analyzed using thematic analysis. The analysis process identified three main themes: Disturbances in daily life, Managing disturbances, and Normalization of daily life. These themes explain the experiences of patients living with enamel disturbances caused by AI and receiving early crown therapy. Experiences include severe pain and sensitivity problems, feelings of embarrassment, and dealing with dental staff that lack knowledge and understanding of their condition. The patients described ways to manage their disturbances and to reduce pain when eating or drinking, and strategies for meeting other people. After definitive treatment with porcelain crown therapy, they described feeling like a normal patient. In conclusion the results showed that adolescents and young adults describe a profound effect of AI on several aspects of their daily life. PMID- 27359124 TI - A Hybrid-Body Containing Constituents of Both P-Bodies and Stress Granules Forms in Response to Hypoosmotic Stress in Saccharomyces cerevisiae. AB - The cytoplasm of the eukaryotic cell is a highly compartmentalized space that contains a variety of ribonucleoprotein (RNP) granules in addition to its complement of membrane-bound organelles. These RNP granules contain specific sets of proteins and mRNAs and form in response to particular environmental and developmental stimuli. Two of the better-characterized of these RNP structures are the stress granule and Processing-body (P-body) that have been conserved from yeast to humans. In this report, we examined the cues regulating stress granule assembly and the relationship between stress granule and P-body foci. These two RNP structures are generally thought to be independent entities in eukaryotic cells. However, we found here that stress granule and P-body proteins were localized to a common or merged granule specifically in response to a hypoosmotic stress. Interestingly, these hybrid-bodies were found to be transient structures that were resolved with time into separate P-body and stress granule foci. In all, these data suggest that the identity of an RNP granule is not absolute and that it can vary depending upon the nature of the induction conditions. Since the activities of a granule are likely influenced by its protein constituency, these observations are consistent with the possibility of RNP granules having distinct functions in different cellular contexts. PMID- 27359127 TI - Rats value time differently on equivalent foraging and delay-discounting tasks. AB - All organisms have to consider consequences that vary through time. Theories explaining how animals handle intertemporal choice include delay-discounting models, in which the value of future rewards is discounted by the delay until receipt, and foraging models, which predict that decision-makers maximize rate of reward. We measured the behavior of rats on a 2-option delay-discounting task and a stay/go foraging task that were equivalent for rate of reward and physical demand. Despite the highly shared features of the tasks, rats were willing to wait much longer on the foraging task than on the delay-discounting task. Moreover, choice performance by rats was less optimal in terms of total reward received on the foraging task compared to the delay-discounting task. We applied a suite of intertemporal choice models to the data but found that we needed a novel model incorporating interactions of decision-making systems to successfully explain behavior. Our findings (a) highlight the importance of factors that historically have been seen as irrelevant and (b) indicate the inadequacy of current general theories of intertemporal choice. (PsycINFO Database Record PMID- 27359128 TI - Sleepless night, restless mind: Effects of sleep deprivation on mind wandering. AB - Sleep deprivation can result in degradation of sustained attention through increased distraction by task-irrelevant exogenous stimuli. However, attentional failures in the sleep-deprived state could also be a result of task-unrelated thoughts (TUTs, or mind wandering). Here, well-rested and sleep-deprived participants performed a visual search task under high and low perceptual load conditions. Thought probes were administered at irregular intervals to gauge the frequency of TUTs and level of meta-awareness of mind wandering. Despite sleep deprived participants reporting more TUTs, they also reported less awareness of TUTs. Although the frequency of TUTs decreased in the high load condition in well rested participants, they were equally frequent across low and high perceptual load conditions in sleep-deprived participants. Together, these findings suggest that sleep deprivation can result in a loss of ability to allocate attentional resources according to task demands consistent with diminished executive control. This may have been exacerbated by reduced meta-awareness. (PsycINFO Database Record PMID- 27359126 TI - Beyond the 'east-west' dichotomy: Global variation in cultural models of selfhood. AB - Markus and Kitayama's (1991) theory of independent and interdependent self construals had a major influence on social, personality, and developmental psychology by highlighting the role of culture in psychological processes. However, research has relied excessively on contrasts between North American and East Asian samples, and commonly used self-report measures of independence and interdependence frequently fail to show predicted cultural differences. We revisited the conceptualization and measurement of independent and interdependent self-construals in 2 large-scale multinational surveys, using improved methods for cross-cultural research. We developed (Study 1: N = 2924 students in 16 nations) and validated across cultures (Study 2: N = 7279 adults from 55 cultural groups in 33 nations) a new 7-dimensional model of self-reported ways of being independent or interdependent. Patterns of global variation support some of Markus and Kitayama's predictions, but a simple contrast between independence and interdependence does not adequately capture the diverse models of selfhood that prevail in different world regions. Cultural groups emphasize different ways of being both independent and interdependent, depending on individualism collectivism, national socioeconomic development, and religious heritage. Our 7 dimensional model will allow future researchers to test more accurately the implications of cultural models of selfhood for psychological processes in diverse ecocultural contexts. (PsycINFO Database Record PMID- 27359129 TI - Does self-control improve with practice? Evidence from a six-week training program. AB - Can self-control be improved through practice? Several studies have found that repeated practice of tasks involving self-control improves performance on other tasks relevant to self-control. However, in many of these studies, improvements after training could be attributable to methodological factors (e.g., passive control conditions). Moreover, the extent to which the effects of training transfer to real-life settings is not yet clear. In the present research, participants (N = 174) completed a 6-week training program of either cognitive or behavioral self-control tasks. We then tested the effects of practice on a range of measures of self-control, including lab-based and real-world tasks. Training was compared with both active and no-contact control conditions. Despite high levels of adherence to the training tasks, there was no effect of training on any measure of self-control. Trained participants did not, for example, show reduced ego depletion effects, become better at overcoming their habits, or report exerting more self-control in everyday life. Moderation analyses found no evidence that training was effective only among particular groups of participants. Bayesian analyses suggested that the data were more consistent with a null effect of training on self-control than with previous estimates of the effect of practice. The implication is that training self-control through repeated practice does not result in generalized improvements in self-control. (PsycINFO Database Record PMID- 27359130 TI - The nature of semantic priming by subliminal spatial words: Embodied or disembodied? AB - Theories of embodied semantics (ES) suggest that a critical part of understanding what a word means consists of simulating the sensorimotor experience related to the word's referent. Some proponents of ES have suggested that sensorimotor activations are mandatory and highly automatic during semantic processing. Evidence supporting this claim comes from masked priming studies showing that unconsciously perceived spatial words (e.g., up, down) can directly modulate action performance on the basis of their meaning. However, a closer look reveals that such priming effects can be explained also in terms of symbolic (disembodied) semantic priming or nonsemantic mechanisms. In this study we sought to understand whether sensorimotor processing takes place during language understanding outside awareness. We used spatial words as a test bed and across 6 experiments we teased apart the possibility that action priming could be explained by: (a) nonsemantic mechanisms, (b) symbolic semantic priming, or (c) embodied semantic priming. The critical finding is that when symbolic and nonsemantic mechanisms were prevented, allowing only for a genuinely embodied semantic priming, no effect was found. Conversely, facilitation emerged in the same experimental paradigm when embodied priming was prevented and symbolic priming was allowed. Despite extensive testing, we found no evidence that unconsciously perceived words can activate sensorimotor processes, although these words are processed up to the semantic level. We thus conclude that sensorimotor activations might need conscious access to emerge during language understanding. (PsycINFO Database Record PMID- 27359132 TI - Characterization of an X-ray mirror mechanical bender for the European XFEL. AB - One of the classical devices used to tune a mirror on an X-ray optical setup is a mechanical bender. This is often designed in such a way that the mirror is held with clamps on both ends; a motor is then used to put a torque on the clamps, inducing a cylindrical shape of the mirror surface. A mechanical bender with this design was recently characterized, to bend a 950 mm-long mirror up to a radius of curvature of 10 km. The characterization was performed using a large-aperture Fizeau interferometer with an angled incidence setup. Some particular and critical effects were investigated, such as calibration, hysteresis, twisting and long-term stability. PMID- 27359131 TI - Strong genetic overlap between executive functions and intelligence. AB - Executive functions (EFs) are cognitive processes that control, monitor, and coordinate more basic cognitive processes. EFs play instrumental roles in models of complex reasoning, learning, and decision making, and individual differences in EFs have been consistently linked with individual differences in intelligence. By middle childhood, genetic factors account for a moderate proportion of the variance in intelligence, and these effects increase in magnitude through adolescence. Genetic influences on EFs are very high, even in middle childhood, but the extent to which these genetic influences overlap with those on intelligence is unclear. We examined genetic and environmental overlap between EFs and intelligence in a racially and socioeconomically diverse sample of 811 twins ages 7 to 15 years (M = 10.91, SD = 1.74) from the Texas Twin Project. A general EF factor representing variance common to inhibition, switching, working memory, and updating domains accounted for substantial proportions of variance in intelligence, primarily via a genetic pathway. General EF continued to have a strong, genetically mediated association with intelligence even after controlling for processing speed. Residual variation in general intelligence was influenced only by shared and nonshared environmental factors, and there remained no genetic variance in general intelligence that was unique of EF. Genetic variance independent of EF did remain, however, in a more specific perceptual reasoning ability. These results provide evidence that genetic influences on general intelligence are highly overlapping with those on EF. (PsycINFO Database Record PMID- 27359133 TI - Undulator beamline optimization with integrated chicanes for X-ray free-electron laser facilities. AB - An optimization of the undulator layout of X-ray free-electron-laser (FEL) facilities based on placing small chicanes between the undulator modules is presented. The installation of magnetic chicanes offers the following benefits with respect to state-of-the-art FEL facilities: reduction of the required undulator length to achieve FEL saturation, improvement of the longitudinal coherence of the FEL pulses, and the ability to produce shorter FEL pulses with higher power levels. Numerical simulations performed for the soft X-ray beamline of the SwissFEL facility show that optimizing the advantages of the layout requires shorter undulator modules than the standard ones. This proposal allows a very compact undulator beamline that produces fully coherent FEL pulses and it makes possible new kinds of experiments that require very short and high-power FEL pulses. PMID- 27359134 TI - Two-color operation of a free-electron laser with a tilted beam. AB - With the successful operation of free-electron lasers (FELs) as user facilities there has been a growing demand for experiments with two photon pulses with variable photon energy and time separation. A configuration of an undulator with variable-gap control and a delaying chicane in the middle of the beamline is proposed. An injected electron beam with a transverse tilt will only yield FEL radiation for the parts which are close to the undulator axis. This allows, after re-aligning and delaying the electron beam, a different part of the bunch to be used to produce a second FEL pulse. This method offers independent control in photon energy and delay. For the parameters of the soft X-ray beamline Athos at the SwissFEL facility the photon energy tuning range is a factor of five with an adjustable delay between the two pulses from -50 to 950 fs. PMID- 27359135 TI - Generation of ultra-large-bandwidth X-ray free-electron-laser pulses with a transverse-gradient undulator. AB - A new and simple method to generate X-ray free-electron-laser radiation with unprecedented spectral bandwidth above the 10% level is presented. The broad bandwidth is achieved by sending a transversely tilted beam through a transverse gradient undulator. The extent of the bandwidth can easily be controlled by variation of the beam tilt or the undulator gradient. Numerical simulations confirm the validity and feasibility of this method. PMID- 27359136 TI - Collimating Montel mirror as part of a multi-crystal analyzer system for resonant inelastic X-ray scattering. AB - Advances in resonant inelastic X-ray scattering (RIXS) have come in lockstep with improvements in energy resolution. Currently, the best energy resolution at the Ir L3-edge stands at ~25 meV, which is achieved using a diced Si(844) spherical crystal analyzer. However, spherical analyzers are limited by their intrinsic reflection width. A novel analyzer system using multiple flat crystals provides a promising way to overcome this limitation. For the present design, an energy resolution at or below 10 meV was selected. Recognizing that the angular acceptance of flat crystals is severely limited, a collimating element is essential to achieve the necessary solid-angle acceptance. For this purpose, a laterally graded, parabolic, multilayer Montel mirror was designed for use at the Ir L3-absorption edge. It provides an acceptance larger than 10 mrad, collimating the reflected X-ray beam to smaller than 100 urad, in both vertical and horizontal directions. The performance of this mirror was studied at beamline 27 ID at the Advanced Photon Source. X-rays from a diamond (111) monochromator illuminated a scattering source of diameter 5 um, generating an incident beam on the mirror with a well determined divergence of 40 mrad. A flat Si(111) crystal after the mirror served as the divergence analyzer. From X-ray measurements, ray tracing simulations and optical metrology results, it was established that the Montel mirror satisfied the specifications of angular acceptance and collimation quality necessary for a high-resolution RIXS multi-crystal analyzer system. PMID- 27359137 TI - The high-resolution absorption spectroscopy branch on the VUV beamline DESIRS at SOLEIL. AB - A VUV absorption spectroscopy facility designed for ultra-high spectral resolution is in operation as a dedicated branch on the DESIRS beamline at Synchrotron SOLEIL. This branch includes a unique VUV Fourier transform spectrometer (FTS) and a dedicated versatile gas sample chamber. The FTS instrument can cover a large UV-VUV spectral range from 4 to 30 eV, with an ultimate line width of 0.08 cm(-1) on a large spectral window, DeltaE/E = 7%, over which all spectral features can be acquired in a multiplex way. The performance can be considered to be a middle ground between broadband moderate resolution spectrometers based on gratings and ultra-high-spectral-resolution VUV tunable-laser-based techniques over very narrow spectral windows. The various available gaseous-sample-handling setups, which function over a wide range of pressures and temperatures, and the acquisition methodology are described. A selection of experimental results illustrates the performance and limitations of the FTS-based facility. PMID- 27359138 TI - Development of a single-cell X-ray fluorescence flow cytometer. AB - An X-ray fluorescence flow cytometer that can determine the total metal content of single cells has been developed. Capillary action or pressure was used to load cells into hydrophilic or hydrophobic capillaries, respectively. Once loaded, the cells were transported at a fixed vertical velocity past a focused X-ray beam. X ray fluorescence was then used to determine the mass of metal in each cell. By making single-cell measurements, the population heterogeneity for metals in the uM to mM concentration range on fL sample volumes can be directly measured, a measurement that is difficult using most analytical methods. This approach has been used to determine the metal composition of 936 individual bovine red blood cells (bRBC), 31 individual 3T3 mouse fibroblasts (NIH3T3) and 18 Saccharomyces cerevisiae (yeast) cells with an average measurement frequency of ~4 cells min( 1). These data show evidence for surprisingly broad metal distributions. Details of the device design, data analysis and opportunities for further sensitivity improvement are described. PMID- 27359139 TI - Continuous-scan capability at SSRL and applications to X-ray diffraction. AB - Typical X-ray diffraction measurements are made by moving a detector to discrete positions in space and then measuring the signal at each stationary position. This step-scanning method can be time-consuming, and may induce vibrations in the measurement system when the motors are accelerated and decelerated at each position. Furthermore, diffraction information between the data points may be missed unless a fine step-scanning is used, which further increases the total measurement time. To utilize beam time efficiently, the motor acceleration and deceleration time should be minimized, and the signal-to-noise ratio should be maximized. To accomplish this, an integrated continuous-scan system was developed at the Stanford Synchrotron Radiation Lightsource (SSRL). The continuous-scan system uses an in-house integrated motor controller system and counter/timer electronics. SPEC software is used to control both the hardware and data acquisition systems. The time efficiency and repeatability of the continuous-scan system were tested using X-ray diffraction from a ZnO powder and compared with the step-scan technique. Advantages and limitations of the continuous-scan system and a demonstration of variable-velocity continuous scan are discussed. PMID- 27359140 TI - Third-order nonlinear and linear time-dependent dynamical diffraction of X-rays in crystals. AB - For the first time the third-order nonlinear time-dependent Takagi's equations of X-rays in crystals are obtained and investigated. The third-order nonlinear and linear time-dependent dynamical diffraction of X-rays spatially restricted in the diffraction plane pulses in crystals is investigated theoretically. A method of solving the linear and the third-order nonlinear time-dependent Takagi's equations is proposed. Based on this method, results of analytical and numerical calculations for both linear and nonlinear diffraction cases are presented and compared. PMID- 27359141 TI - Multi-speckle X-ray photon correlation spectroscopy in the ultra-small-angle X ray scattering range. AB - Multi-speckle X-ray photon correlation spectroscopy (XPCS) measurements in the ultra-small-angle range are performed using a long pinhole collimation instrument in combination with two-dimensional photon-counting and high-sensitivity imaging detectors. The feasibility of the presented setup to measure dynamics on different time and length scales pertinent to colloidal systems is shown. This setup offers new research opportunities, such as for example in the investigation of non-equilibrium dynamics in optically opaque, complex systems over length scales from tens of nanometres to several micrometres. In addition, due to the short duration of the X-ray exposure involved in the ultra-small-angle range, possible radiation-induced effects are alleviated. Furthermore, the performance of two different detectors, a photon-counting Pilatus 300K and an integrating FReLoN CCD, are compared, and their applicability for accurate XPCS measurements is demonstrated. PMID- 27359142 TI - Synchrotron X-ray microfluorescence measurement of metal distributions in Phragmites australis root system in the Yangtze River intertidal zone. AB - This study investigates the distributions of Br, Ca, Cl, Cr, Cu, K, Fe, Mn, Pb, Ti, V and Zn in Phragmites australis root system and the function of Fe nanoparticles in scavenging metals in the root epidermis using synchrotron X-ray microfluorescence, synchrotron transmission X-ray microscope measurement and synchrotron X-ray absorption near-edge structure techniques. The purpose of this study is to understand the mobility of metals in wetland plant root systems after their uptake from rhizosphere soils. Phragmites australis samples were collected in the Yangtze River intertidal zone in July 2013. The results indicate that Fe nanoparticles are present in the root epidermis and that other metals correlate significantly with Fe, suggesting that Fe nanoparticles play an important role in metal scavenging in the epidermis. PMID- 27359143 TI - Vanadium K-edge XANES in vanadium-bearing model compounds: a full multiple scattering study. AB - A systematic study is presented on a set of vanadium-bearing model compounds, representative of the most common V coordination geometries and oxidation states, analysed by means of vanadium K-edge X-ray absorption near-edge spectroscopy calculations in the full multiple scattering (FMS) framework. Analysis and calibration of the free parameters of the theory under the muffin-tin approximation (muffin-tin overlap and interstitial potential) have been carried out by fitting the experimental spectra using the MXAN program. The analysis shows a correlation of the fit parameters with the V coordination geometry and oxidation state. By making use of this correlation it is possible to approach the study of unknown V-bearing compounds with useful preliminary information. PMID- 27359144 TI - Novel silica stabilization method for the analysis of fine nanocrystals using coherent X-ray diffraction imaging. AB - High-energy X-ray Bragg coherent diffraction imaging (BCDI) is a well established synchrotron-based technique used to quantitatively reconstruct the three dimensional morphology and strain distribution in nanocrystals. The BCDI technique has become a powerful analytical tool for quantitative investigations of nanocrystals, nanotubes, nanorods and more recently biological systems. BCDI has however typically failed for fine nanocrystals in sub-100 nm size regimes - a size routinely achievable by chemical synthesis - despite the spatial resolution of the BCDI technique being 20-30 nm. The limitations of this technique arise from the movement of nanocrystals under illumination by the highly coherent beam, which prevents full diffraction data sets from being acquired. A solution is provided here to overcome this problem and extend the size limit of the BCDI technique, through the design of a novel stabilization method by embedding the fine nanocrystals into a silica matrix. Chemically synthesized FePt nanocrystals of maximum dimension 20 nm and AuPd nanocrystals in the size range 60-65 nm were investigated with BCDI measurement at beamline 34-ID-C of the APS, Argonne National Laboratory. Novel experimental methodologies to elucidate the presence of strain in fine nanocrystals are a necessary pre-requisite in order to better understand strain profiles in engineered nanocrystals for novel device development. PMID- 27359146 TI - Visualization of mouse spinal cord intramedullary arteries using phase- and attenuation-contrast tomographic imaging. AB - Many spinal cord circulatory disorders present the substantial involvement of small vessel lesions. The central sulcus arteries supply nutrition to a large part of the spinal cord, and, if not detected early, lesions in the spinal cord will cause irreversible damage to the function of this organ. Thus, early detection of these small vessel lesions could potentially facilitate the effective diagnosis and treatment of these diseases. However, the detection of such small vessels is beyond the capability of current imaging techniques. In this study, an imaging method is proposed and the potential of phase-contrast imaging (PCI)- and attenuation-contrast imaging (ACI)-based synchrotron radiation for high-resolution tomography of intramedullary arteries in mouse spinal cord is validated. The three-dimensional vessel morphology, particularly that of the central sulcus arteries (CSA), detected with these two imaging models was quantitatively analyzed and compared. It was determined that both PCI- and ACI based synchrotron radiation can be used to visualize the physiological arrangement of the entire intramedullary artery network in the mouse spinal cord in both two dimensions and three dimensions at a high-resolution scale. Additionally, the two-dimensional and three-dimensional vessel morphometric parameter measurements obtained with PCI are similar to the ACI data. Furthermore, PCI allows efficient and direct discrimination of the same branch level of the CSA without contrast agent injection and is expected to provide reliable biological information regarding the intramedullary artery. Compared with ACI, PCI might be a novel imaging method that offers a powerful imaging platform for evaluating pathological changes in small vessels and may also allow better clarification of their role in neurovascular disorders. PMID- 27359145 TI - Guiding synchrotron X-ray diffraction by multimodal video-rate protein crystal imaging. AB - Synchronous digitization, in which an optical sensor is probed synchronously with the firing of an ultrafast laser, was integrated into an optical imaging station for macromolecular crystal positioning prior to synchrotron X-ray diffraction. Using the synchronous digitization instrument, second-harmonic generation, two photon-excited fluorescence and bright field by laser transmittance were all acquired simultaneously with perfect image registry at up to video-rate (15 frames s(-1)). A simple change in the incident wavelength enabled simultaneous imaging by two-photon-excited ultraviolet fluorescence, one-photon-excited visible fluorescence and laser transmittance. Development of an analytical model for the signal-to-noise enhancement afforded by synchronous digitization suggests a 15.6-fold improvement over previous photon-counting techniques. This improvement in turn allowed acquisition on nearly an order of magnitude more pixels than the preceding generation of instrumentation and reductions of well over an order of magnitude in image acquisition times. These improvements have allowed detection of protein crystals on the order of 1 um in thickness under cryogenic conditions in the beamline. These capabilities are well suited to support serial crystallography of crystals approaching 1 um or less in dimension. PMID- 27359148 TI - X-ray nanotomography and focused-ion-beam sectioning for quantitative three dimensional analysis of nanocomposites. AB - Knowing the relationship between three-dimensional structure and properties is paramount for complete understanding of material behavior. In this work, the internal nanostructure of micrometer-size (~10 um) composite Ni/Al particles was analyzed using two different approaches. The first technique, synchrotron-based X ray nanotomography, is a nondestructive method that can attain resolutions of tens of nanometers. The second is a destructive technique with sub-nanometer resolution utilizing scanning electron microscopy combined with an ion beam and 'slice and view' analysis, where the sample is repeatedly milled and imaged. The obtained results suggest that both techniques allow for an accurate characterization of the larger-scale structures, while differences exist in the characterization of the smallest features. Using the Monte Carlo method, the effective resolution of the X-ray nanotomography technique was determined to be ~48 nm, while focused-ion-beam sectioning with 'slice and view' analysis was ~5 nm. PMID- 27359149 TI - Optimization of tomographic reconstruction workflows on geographically distributed resources. AB - New technological advancements in synchrotron light sources enable data acquisitions at unprecedented levels. This emergent trend affects not only the size of the generated data but also the need for larger computational resources. Although beamline scientists and users have access to local computational resources, these are typically limited and can result in extended execution times. Applications that are based on iterative processing as in tomographic reconstruction methods require high-performance compute clusters for timely analysis of data. Here, time-sensitive analysis and processing of Advanced Photon Source data on geographically distributed resources are focused on. Two main challenges are considered: (i) modeling of the performance of tomographic reconstruction workflows and (ii) transparent execution of these workflows on distributed resources. For the former, three main stages are considered: (i) data transfer between storage and computational resources, (i) wait/queue time of reconstruction jobs at compute resources, and (iii) computation of reconstruction tasks. These performance models allow evaluation and estimation of the execution time of any given iterative tomographic reconstruction workflow that runs on geographically distributed resources. For the latter challenge, a workflow management system is built, which can automate the execution of workflows and minimize the user interaction with the underlying infrastructure. The system utilizes Globus to perform secure and efficient data transfer operations. The proposed models and the workflow management system are evaluated by using three high-performance computing and two storage resources, all of which are geographically distributed. Workflows were created with different computational requirements using two compute-intensive tomographic reconstruction algorithms. Experimental evaluation shows that the proposed models and system can be used for selecting the optimum resources, which in turn can provide up to 3.13* speedup (on experimented resources). Moreover, the error rates of the models range between 2.1 and 23.3% (considering workflow execution times), where the accuracy of the model estimations increases with higher computational demands in reconstruction tasks. PMID- 27359147 TI - Specimen preparation for cryogenic coherent X-ray diffraction imaging of biological cells and cellular organelles by using the X-ray free-electron laser at SACLA. AB - Coherent X-ray diffraction imaging (CXDI) allows internal structures of biological cells and cellular organelles to be analyzed. CXDI experiments have been conducted at 66 K for frozen-hydrated biological specimens at the SPring-8 Angstrom Compact Free-Electron Laser facility (SACLA). In these cryogenic CXDI experiments using X-ray free-electron laser (XFEL) pulses, specimen particles dispersed on thin membranes of specimen disks are transferred into the vacuum chamber of a diffraction apparatus. Because focused single XFEL pulses destroy specimen particles at the atomic level, diffraction patterns are collected through raster scanning the specimen disks to provide fresh specimen particles in the irradiation area. The efficiency of diffraction data collection in cryogenic experiments depends on the quality of the prepared specimens. Here, detailed procedures for preparing frozen-hydrated biological specimens, particularly thin membranes and devices developed in our laboratory, are reported. In addition, the quality of the frozen-hydrated specimens are evaluated by analyzing the characteristics of the collected diffraction patterns. Based on the experimental results, the internal structures of the frozen-hydrated specimens and the future development for efficient diffraction data collection are discussed. PMID- 27359150 TI - Synchrotron X-ray CT characterization of titanium parts fabricated by additive manufacturing. Part I. Morphology. AB - Synchrotron X-ray tomography has been applied to the study of titanium parts fabricated by additive manufacturing (AM). The AM method employed here was the Arcam EBM((r)) (electron beam melting) process which uses powdered titanium alloy, Ti64 (Ti alloy with approximately 6%Al and 4%V), as the feed and an electron beam for the sintering/welding. The experiment was conducted on the Imaging and Medical Beamline of the Australian Synchrotron. Samples were chosen to examine the effect of build direction and complexity of design on the surface morphology and final dimensions of the piece. PMID- 27359152 TI - A method of hard X-ray phase-shifting digital holography. AB - A new method of phase-shifting digital holography is demonstrated in the hard X ray region. An in-line-type phase-shifting holography setup was installed in a 6.80 keV hard X-ray synchrotron beamline. By placing a phase plate consisting of a hole and a band at the focusing point of a Fresnel lens, the relative phase of the reference and objective beams could be successfully shifted for use with a three-step phase-shift algorithm. The system was verified by measuring the shape of a gold test pattern and a silica sphere. PMID- 27359151 TI - Synchrotron X-ray CT characterization of titanium parts fabricated by additive manufacturing. Part II. Defects. AB - Synchrotron X-ray tomography (SXRT) has been applied to the study of defects within three-dimensional printed titanium parts. These parts were made using the Arcam EBM((r)) (electron beam melting) process which uses powdered titanium alloy, Ti64 (Ti alloy with approximately 6%Al and 4%V) as the feed and an electron beam for the sintering/welding. The experiment was conducted on the Imaging and Medical Beamline of the Australian Synchrotron. The samples represent a selection of complex shapes with a variety of internal morphologies. Inspection via SXRT has revealed a number of defects which may not otherwise have been seen. The location and nature of such defects combined with detailed knowledge of the process conditions can contribute to understanding the interplay between design and manufacturing strategy. This fundamental understanding may subsequently be incorporated into process modelling, prediction of properties and the development of robust methodologies for the production of defect-free parts. PMID- 27359153 TI - A deformation rig for synchrotron microtomography studies of geomaterials under conditions down to 10 km depth in the Earth. AB - A hard X-ray transparent triaxial deformation apparatus, called HADES, has been developed by Sanchez Technologies and installed on the microtomography beamline ID19 at the European Radiation Synchrotron Facility (ESRF). This rig can be used for time-lapse microtomography studies of the deformation of porous solids (rocks, ceramics, metallic foams) at conditions of confining pressure to 100 MPa, axial stress to 200 MPa, temperature to 250 degrees C, and controlled aqueous fluid flow. It is transparent to high-energy X-rays above 60 keV and can be used for in situ studies of coupled processes that involve deformation and chemical reactions. The rig can be installed at synchrotron radiation sources able to deliver a high-flux polychromatic beam in the hard X-ray range to acquire tomographic data sets with a voxel size in the range 0.7-6.5 um in less than two minutes. PMID- 27359154 TI - The vacuum ultraviolet beamline/endstations at NSRL dedicated to combustion research. AB - An undulator-based vacuum ultraviolet (VUV) beamline (BL03U), intended for combustion chemistry studies, has been constructed at the National Synchrotron Radiation Laboratory (NSRL) in Hefei, China. The beamline is connected to the newly upgraded Hefei Light Source (HLS II), and could deliver photons in the 5-21 eV range, with a photon flux of 10(13) photons s(-1) at 10 eV when the beam current is 300 mA. The monochromator of the beamline is equipped with two gratings (200 lines mm(-1) and 400 lines mm(-1)) and its resolving power is 3900 at 7.3 eV for the 200 lines mm(-1) grating and 4200 at 14.6 eV for the 400 lines mm(-1) grating. The beamline serves three endstations which are designed for respective studies of premixed flame, fuel pyrolysis in flow reactor, and oxidation in jet-stirred reactor. Each endstation contains a reactor chamber, an ionization chamber where the molecular beam intersects with the VUV light, and a home-made reflectron time-of-flight mass spectrometer. The performance of the beamline and endstations with some preliminary results is presented here. The ability to detect reactive intermediates (e.g. H, O, OH and hydroperoxides) is advantageous in combustion chemistry research. PMID- 27359155 TI - HiSPoD: a program for high-speed polychromatic X-ray diffraction experiments and data analysis on polycrystalline samples. AB - A high-speed X-ray diffraction technique was recently developed at the 32-ID-B beamline of the Advanced Photon Source for studying highly dynamic, yet non repeatable and irreversible, materials processes. In experiments, the microstructure evolution in a single material event is probed by recording a series of diffraction patterns with extremely short exposure time and high frame rate. Owing to the limited flux in a short pulse and the polychromatic nature of the incident X-rays, analysis of the diffraction data is challenging. Here, HiSPoD, a stand-alone Matlab-based software for analyzing the polychromatic X-ray diffraction data from polycrystalline samples, is described. With HiSPoD, researchers are able to perform diffraction peak indexing, extraction of one dimensional intensity profiles by integrating a two-dimensional diffraction pattern, and, more importantly, quantitative numerical simulations to obtain precise sample structure information. PMID- 27359156 TI - Developmental changes in children's normative reasoning across learning contexts and collaborative roles. AB - What influences children's normative judgments of conventional rules at different points in development? The current study explored the effects of two contextual factors on children's normative reasoning: the way in which the rules were learned and whether the rules apply to the self or others. Peer dyads practiced a novel collaborative board game comprising two complementary roles. Dyads were either taught both the prescriptive (i.e., what to do) and proscriptive (i.e., what not to do) forms of the rules, taught only the prescriptive form of the rules, or created the rules themselves. Children then judged whether third parties were violating or conforming to the rules governing their own roles and their partner's roles. Early school-aged children's (6- to 7-year-olds; N = 60) normative judgments were strongest when they had been taught the rules (with or without the proscriptive form), but were more flexible for rules they created themselves. Preschool-aged children's (4- to 5-year-olds; N = 60) normative judgments, however, were strongest when they were taught both the prescriptive and proscriptive forms of the rules. Additionally, preschoolers exhibited stronger normative judgments when the rules governed their own roles rather than their partner's roles, whereas school-aged children treated all rules as equally normative. These results demonstrate that children's normative reasoning is contingent on contextual factors of the learning environment and, moreover, highlight 2 specific areas in which children's inferences about the normativity of conventions strengthen over development. (PsycINFO Database Record PMID- 27359157 TI - It's payback time: Preschoolers selectively request resources from someone they had benefitted. AB - Expectations that others will reciprocate to the benefits they received from us play a crucial role for the establishment of stable reciprocal exchange within social relationships. In the current study, 3- to 5-year-old preschool children allocated in a first phase more resources to one recipient than to another recipient. Subsequently, they had the possibility to ask one of them for valuable resources. The results of Experiment 1 show that preschool children expect others to reciprocate and strategically ask the ones they benefitted more to share with them. Experiment 2 demonstrates that there was no selective resource request when the recipients were absent during children's resource allocations. Experiment 3 showed that children focused on the absolute amount of resources given to the recipients, but did not monitor their own relative generosity in judging to whom of the recipients they had been nicer. This study provides first evidence that preschool children possess reciprocity expectations and point thus to the strategic nature of early social behavior. (PsycINFO Database Record PMID- 27359158 TI - Six-Step Synthesis of Alcyopterosin A, a Bioactive Illudalane Sesquiterpene with a gem-Dimethylcyclopentane Ring. AB - Strategic pairing of ring openings and cycloisomerization provides rapid and efficient "open and shut" entry into sparsely functionalized illudalanes, as exemplified here in the context of a six-step synthesis of alcyopterosin A. Key steps include a tandem ring-opening fragmentation/olefination process for preparing a neopentyl-tethered 1,6-enyne, ring-opening olefination telescoped with alkyne homologation, and Rh-catalyzed oxidative cycloisomerization. PMID- 27359159 TI - Factors predictive of critical value of hypocalcemia after total parathyroidectomy without autotransplantation in patients with secondary hyperparathyroidism. AB - BACKGROUND: Severe hypocalcemia is the most dangerous complication occurring after total parathyroidectomy without autotransplantation (TPTX) for secondary hyperparathyroidism (SHPT). We aim to identify the prevalence and potential risk factors of very severe hypocalcemia in patients with SHPT undergoing TPTX. METHODS: From April 2012 to August 2015, 157 patients with SHPT undergoing TPTX were reviewed. The critical value of hypocalcemia (CVH) was postoperative serum Ca(2+) levels of <=1.5 mmol/L. RESULTS: Univariate analysis showed that patients in the CVH group were significantly younger than those in the non-CVH group. Sex ratio was significantly different between the two groups. The CVH group had significantly higher levels of preoperative PTH and ALP. Male sex and preoperative levels of PTH and ALP were significant independent risk factors by logistic regression analysis. CONCLUSIONS: Male sex, preoperative PTH and ALP were significantly associated with CVH in patients with SHPT undergoing TPTX. PMID- 27359160 TI - Superexchange Charge Transport in Loaded Metal Organic Frameworks. AB - In the past, nanoporous metal-organic frameworks (MOFs) have been mostly studied for their huge potential with regard to gas storage and separation. More recently, the discovery that the electrical conductivity of a widely studied, highly insulating MOF, HKUST-1, improves dramatically when loaded with guest molecules has triggered a huge interest in the charge carrier transport properties of MOFs. The observed high conductivity, however, is difficult to reconcile with conventional transport mechanisms: neither simple hopping nor band transport models are consistent with the available experimental data. Here, we combine theoretical results and new experimental data to demonstrate that the observed conductivity can be explained by an extended hopping transport model including virtual hops through localized MOF states or molecular superexchange. Predictions of this model agree well with precise conductivity measurements, where experimental artifacts and the influence of defects are largely avoided by using well-defined samples and the Hg-drop junction approach. PMID- 27359161 TI - Fossil Fuel Combustion-Related Emissions Dominate Atmospheric Ammonia Sources during Severe Haze Episodes: Evidence from (15)N-Stable Isotope in Size-Resolved Aerosol Ammonium. AB - The reduction of ammonia (NH3) emissions is urgently needed due to its role in aerosol nucleation and growth causing haze formation during its conversion into ammonium (NH4(+)). However, the relative contributions of individual NH3 sources are unclear, and debate remains over whether agricultural emissions dominate atmospheric NH3 in urban areas. Based on the chemical and isotopic measurements of size-resolved aerosols in urban Beijing, China, we find that the natural abundance of (15)N (expressed using delta(15)N values) of NH4(+) in fine particles varies with the development of haze episodes, ranging from -37.10/00 to -21.70/00 during clean/dusty days (relative humidity: ~ 40%), to -13.10/00 to +5.80/00 during hazy days (relative humidity: 70-90%). After accounting for the isotope exchange between NH3 gas and aerosol NH4(+), the delta(15)N value of the initial NH3 during hazy days is found to be -14.50/00 to -1.60/00, which indicates fossil fuel-based emissions. These emissions contribute 90% of the total NH3 during hazy days in urban Beijing. This work demonstrates the analysis of delta(15)N values of aerosol NH4(+) to be a promising new tool for partitioning atmospheric NH3 sources, providing policy makers with insights into NH3 emissions and secondary aerosols for regulation in urban environments. PMID- 27359162 TI - Truncated Transition Densities for Analysis of (Nonlinear) Optical Properties of carbo-Chromophores. AB - The optical properties of several quadrupolar carbo-benzene derivatives are investigated at various levels of calculation (TDDFT and CASPT2) and analyzed using a new theoretical tool here disclosed: The "visualization" of the transition dipole moment from the transition density truncated to the main monoexcitations involved in the electronic transition (TTD). The experimental or calculated one-photon UV-visible absorption spectra of the carbo-benzene derivatives fit with the Gouterman model originally proposed for porphyrins, where the first four excited states involve linear combinations of monoexcitations of the same four frontier molecular orbitals. The relative intensities of the absorption bands are analyzed from the transition dipole moments calculated from the TTDs and an analogy between porphyrins and carbo benzenes is argued. The two-photon absorption (TPA) cross section related to the third-order nonlinear optical response is calculated for each two-photon-allowed excited state |f? from the contribution of all possible intermediate excited states |i? using the "sum-over-state" (SOS) scheme. The quadrupolar carbo-benzene derivatives fit into the three-level model, as their TPA cross section exhibits a dominant contribution of one of the intermediate excited states. The origin of TPA efficiency (enhancement) upon carbo-merisation of the C-C link to the para substituents is discussed from the excitation energies of the intermediate and final excited states and from the two corresponding transition dipole moments (MU0i and MUif). The latter may be calculated from the TTDs. PMID- 27359163 TI - Penipyridones A-F, Pyridone Alkaloids from Penicillium funiculosum. AB - Six new pyridone alkaloids, named penipyridones A-F (1-6), were isolated from the fermentation broth of an Antarctic moss-derived fungus, Penicillium funiculosum GWT2-24. Their structures were elucidated from extensive NMR and MS data. Although they possess the same major chromophore and some of them presented almost mirror ECD spectra, their absolute configurations were found to be uniformly S, as evidenced by X-ray single-crystal diffraction analysis, stereocontrolled total synthesis, and chemical conversions. TDDFT-ECD calculations of compounds 3 and 6 revealed that subtle conformational changes are responsible for the significantly different ECD curves. None of the compounds were cytotoxic (IC50 > 50 MUM), while compounds 1, 2, 5, and 7 elicited lipid lowering activity in HepG2 hepatocytes. PMID- 27359164 TI - Three Randomized Effectiveness Trials - One Question: Can Callous-Unemotional Traits in Children Be Altered? AB - Children with conduct problems and callous-unemotional (CU) traits are at risk for multiple problems. Outcome research and mediation analyses testing for mechanisms of change in CU traits have been limited. We examined whether parent training-in a short-term (Brief Parent Training; BPT) or a comprehensive format (Parent Management Training, Oregon Model; PMTO)-or child-directed social skills training (Individual Social Skills Training [ISST]) produced positive effects on CU traits. In mediation models we tested parenting practices as mechanisms of change for CU traits. We pooled data from three randomized effectiveness trials, and 551 families were included in this study. Families had children between 3 and 12 years of age and displayed emerging or present conduct problems at home, day care, or school (BPT M age = 7.28, 31.9% girls; PMTO M age = 8.56, 36.5% girls; ISST M age = 7.64, 19.7% girls). Assessments were completed preintervention, postintervention, and at follow-up (6 months following intervention). Both BPT (d = .32) and PMTO (d = .39) had positive effects on CU traits at posttest, whereas ISST did not (d = -.06). At follow-up, only PMTO produced a significant effect (d = .48) on CU traits. A significant indirect effect on CU traits emerged by positive parenting. Both parent training conditions outperformed ISST. Only PMTO maintained its effects at follow-up. The findings suggest that PMTO can reduce CU traits and that improved positive parenting is associated with positive outcomes for children's CU traits. PMID- 27359165 TI - Hot-Press-Assisted Adhesions between Polyimide Films and Titanium Plates Utilizing Coating Layers of Silane Coupling Agents. AB - The development of low material-consuming adhesion techniques for different kinds of materials such as polymers and metals is important for the realization of sustainable societies. This study demonstrates that coating layers, expected to be formed as self-assembled monolayers, of silane coupling agents can act as adhesion layers at the polymer film-metal plate interfaces. Polyimide films were alkaline hydrolyzed to generate carboxy groups on their surfaces, whereas titanium plate surfaces were treated with the aminosilanes to form their coating layers thereon. These modified surfaces were placed in contact with each other and then hot pressed, which resulted in adhesion between them. An examination of the adhesion strength using lap shear tests and surface characterization of the prepared surfaces using X-ray photoelectron spectroscopy and other techniques indicated the formation of ionic bonds and/or amide bonds between the carboxy groups of the PI film surfaces and the amino groups immobilized on the titanium plate surfaces. The activation of the carboxy groups using N-hydroxysuccinimide resulted in adhesion obtaining a water-resistant property, which supported the increase in amide bond formation. On the basis of the results, the adhesion mechanism and the possible breaking points upon the breaking of adhesions are proposed. PMID- 27359166 TI - Further insight into BRUTUS domain composition and functionality. AB - BRUTUS (BTS) is a hemerythrin (HHE) domain containing E3 ligase that facilitates the degradation of POPEYE-like (PYEL) proteins in a proteasomal-dependent manner. Deletion of BTS HHE domains enhances BTS stability in the presence of iron and also complements loss of BTS function, suggesting that the HHE domains are critical for protein stability but not for enzymatic function. The RING E3 domain plays an essential role in BTS' capacity to both interact with PYEL proteins and to act as an E3 ligase. Here we show that removal of the RING domain does not complement loss of BTS function. We conclude that enzymatic activity of BTS via the RING domain is essential for response to iron deficiency in plants. Further, we analyze possible BTS domain structure evolution and predict that the combination of domains found in BTS is specific to photosynthetic organisms, potentially indicative of a role for BTS and its orthologs in mitigating the iron related challenges presented by photosynthesis. PMID- 27359167 TI - Suicide Rates by Occupational Group - 17 States, 2012. AB - In 2012, approximately 40,000 suicides were reported in the United States, making suicide the 10th leading reported cause of death for persons aged >=16 years (1). From 2000 to 2012, rates of suicide among persons in this age group increased 21.1%, from 13.3 per 100,000 to 16.1 (1). To inform suicide prevention efforts, CDC analyzed suicide by occupational group, by ascribing occupational codes to 12,312 suicides in 17 states in 2012 from the National Violent Death Reporting System (NVDRS) (2). The frequency of suicide in different occupational groups was examined, and rates of suicide were calculated by sex and age group for these categories. Persons working in the farming, fishing, and forestry group had the highest rate of suicide overall (84.5 per 100,000 population) and among males (90.5); the highest rates of suicide among females occurred among those working in protective service occupations (14.1). Overall, the lowest rate of suicide (7.5) was found in the education, training, and library occupational group. Suicide prevention approaches directed toward persons aged >=16 years that enhance social support, community connectedness, access to preventive services, and the reduction of stigma and barriers to help-seeking are needed. PMID- 27359168 TI - Investigating non-specific binding to chemically engineered sensor surfaces using liposomes as models. AB - Nanoparticles are ubiquitously used for signal enhancement in (bio)sensors, but their true possible performance is typically hampered by non-specific binding. A better understanding of the nature and the prevention of non-specific binding through surface engineering of the particles and sensor surfaces is needed to intelligently design (bio)sensors and potentially avoid bulk blocking methods. Hence, two types of liposomes were used as model for signal-enhancing nanoparticles. Their surface was engineered to bear negative surface charge. One type was synthesized with additional 6 mol% -COOH groups. Their interaction with four typical chemically modified sensor surfaces was then mechanistically characterized by surface plasmon resonance (SPR) spectroscopy. It was shown that the non-specific binding can be described with Langmuir isotherms providing quantitative information of dissociation constants and surface loading with especially high correlation coefficients (>0.97) for all the studied sensor surfaces modified with hydrophilic alkane thiols. By tailoring the sensor surface chemistry, non-specific binding was significantly minimized. Here, carboxyl- or methyl-terminated surfaces performed best. In fact, the pairing of -COOH groups on the sensor surface with -COOH groups on the liposomes almost completely eliminated non-specific binding, resulting in a SPR signal change of only 1 mRIU (refractive index unit) at 100 MUM phospholipid concentration. Surprisingly though, -OH groups on the surface, which are also commonly used in sensing applications, did not lead to decreased adsorption, but caused significant signal changes (4 mRIU at 100 MUM phospholipid) due to non-specific binding. Overall, the mechanistic studies presented here demonstrate that by careful design of the nanoparticle surface and by choosing sensor surfaces with terminal -CH3 or -COOH groups, improved sensing (micro)systems with very low non-specific adsorption can be obtained. PMID- 27359169 TI - Total Synthesis of Plakilactones C, B and des-Hydroxyplakilactone B by the Oxidative Cleavage of Gracilioether Furanylidenes. AB - A chemoselective oxidative cleavage of synthetic gracilioether B, 11-epi gracilioether C benzoate, and des-hydroxygracilioether C with pyridinium chlorochromate, which proceeds with loss of the furanyl acetate, has enabled total synthesis and stereochemical elucidation of the marine sponge metabolites (4R,6R)-plakilactone C, (4R,6R,9R)-plakilactone B, and (4R,6R)-des hydroxyplakilactone B. des-Hydroxygracilioether C, the putative biosynthetic precursor to hippolachnin A, was also found to undergo a facile ene cyclization on treatment with SnCl4. PMID- 27359170 TI - Sex and Gender Roles in Relation to Mental Health and Allostatic Load. AB - OBJECTIVES: Beyond male/female binaries, gender roles represent masculine and feminine traits that we assimilate and enact throughout life span development. Bem proposed that "androgynous" individuals adeptly adapt to different contexts by alternating from a strong repertoire of both masculine and feminine gender roles. By contrast, "undifferentiated" individuals may not adapt as well to social norms because of weak self-endorsed masculinity and femininity. METHODS: Among 204 adults (mean [standard error] age = 40.4 [0.9] years; 70% women) working in a psychiatric hospital, we hypothesized that androgynous individuals would present better mental health and less physiological dysregulations known as allostatic load (AL) than undifferentiated individuals. AL was indexed using 20 biomarkers using the conventional "all-inclusive" formulation that ascribes cutoffs without regard for sex or an alternative "sex-specific" formulation with cutoffs tailored for each sex separately while controlling for sex hormones (testosterone, estradiol, progesterone). Well-validated questionnaires were used. RESULTS: Independent of sex, androgynous individuals experienced higher self esteem and well-being and lower depressive symptoms than did undifferentiated individuals. Men manifested higher AL than did women using the all-inclusive AL index (p = .044, etaP = 0.025). By contrast, the sex-specific AL algorithm unmasked a sex by gender roles interaction for AL (p = .043, etaP = 0.048): with the highest AL levels in undifferentiated men. Analysis using a gender index based on seven gendered constructs revealed that a greater propensity toward feminine characteristics correlated only with elevated sex-specific AL (r = 0.163, p = .025). CONCLUSIONS: Beyond providing psychobiological evidence for Bem's theory, this study highlights how sex-specific AL formulations detect the effects of sociocultural gender. PMID- 27359171 TI - Kynurenine and Tryptophan Levels in Patients With Schizophrenia and Elevated Antigliadin Immunoglobulin G Antibodies. AB - OBJECTIVE: Several studies have reported an association between nonceliac gluten sensitivity and schizophrenia. Immune and kynurenine (KYN) pathways have also been implicated in the pathophysiology of schizophrenia, and certain proinflammatory immune mediators may increase KYN and reduce tryptophan (TRP) levels. METHODS: We measured serum antigliadin immunoglobulin G (IgG), KYN, and TRP in 950 patients with schizophrenia. Patients with antibody level at the 90th percentile or higher of control participants (21.9% of all patients) were classified as having elevated antigliadin IgG. Independent t tests and linear regression models were used to compare TRP, KYN, and KYN-TRP ratio (indicator of TRP metabolism) between patients with and those without elevated antigliadin IgG. The correlation between antigliadin IgG and TRP, KYN, and the ratio was also evaluated in the patients. RESULTS: KYN and KYN-TRP ratio were higher in patients with elevated antigliadin IgG (geometric mean [standard deviation {SD}] = 2.65 [0.25] umol/L versus 2.25 [0.23] umol/L [p < .001] and 0.05 [0.26] versus 0.04 [0.25; p = .001] respectively), findings robust to adjustment for potential demographic and clinical confounders. Antigliadin IgG positively correlated with KYN and KYN-TRP ratio (r = 0.12, p < .001; r = 0.11, p = .002). TRP did not differ between the two groups and did not correlate with antigliadin IgG. CONCLUSIONS: Our results connect nonceliac gluten sensitivity with the KYN pathway of TRP metabolism in psychotic illness and hint toward potential individualized treatment targets. PMID- 27359172 TI - Impact of Maternal Lifetime Interpersonal Trauma on Children's Asthma: Mediation Through Maternal Active Asthma During Pregnancy. AB - OBJECTIVE: Traumatic stressors, including child abuse and/or interpersonal violence over a woman's lifecourse, can affect the health of her children. This study examines the associations between maternal lifetime interpersonal trauma (IPT) and children's asthma by age 6 years (n = 857). METHODS: Pregnant women completed the Revised Conflict Tactics Scale; IPT exposure was categorized as unexposed (55%), early (childhood and/or teen years only, 25%), late (adulthood and/or index pregnancy, 7%), and chronic (early and late, 13%). Clinician diagnosed asthma in children was reported by mothers at each follow-up visit until the child reached age 6 years. We examined the effects of maternal IPT categories and child's asthma using logistic regression. Using structural equation models, we also examined indirect relationships between maternal chronic IPT and child asthma operating through active asthma in pregnancy, prepregnancy BMI, prenatal smoking, and/or increased exposure to other adverse life events or environmental toxins prenatally. Effect modification by the child's sex was examined. RESULTS: Mothers were primarily Hispanic (55%) or black (30%) with less than high school education (62%). In logistic regression models, chronic maternal IPT (compared with unexposed) was associated with asthma in boys (odds ratio = 2.87, 95% confidence interval = 1.48-5.57) but not girls (odds ratio = 0.69, 95% confidence interval = 0.23-2.12; pinteraction = .042). In structural equation models, chronic IPT was associated with maternal active asthma in pregnancy (beta = 0.59, p < .001), maternal active asthma was associated with children's asthma (beta = 0.20, p = .009), and the total indirect effect for this path was significant (beta = 0.12, p = .031). Associations were most evident among boys. CONCLUSIONS: Mothers' history of chronic IPT was associated with asthma in boys. This association was mediated through active maternal asthma in pregnancy. PMID- 27359173 TI - Molecular Mechanisms of Stress-Induced Myocardial Injury in a Rat Model Simulating Posttraumatic Stress Disorder. AB - OBJECTIVE: Posttraumatic stress disorder (PTSD) is an independent risk factor for cardiovascular diseases. This study investigated the molecular mechanisms underlying myocardial injury induced by simulated PTSD. METHODS: Sprague-Dawley rats were randomly divided into two groups: control group (n = 18) and PTSD group (n = 30). The PTSD model was replicated using the single prolonged stress (SPS) method. On the 14th day poststress, the apoptotic cells in myocardium were assessed using both TUNEL method and transmission electron microscopy; the protein levels of the endoplasmic reticulum stress (ERS) molecules were measured by using Western blotting analysis. RESULTS: Exposure to SPS resulted in characteristic morphologic changes of apoptosis in cardiomyocytes assessed by transmission electron microscopy. Moreover, TUNEL staining was also indicative of the elevated apoptosis rate of cardiomyocytes from the SPS rats (30.69% versus 7.26%, p < .001). Simulated PTSD also induced ERS in myocardium, demonstrated by up-regulation of protein levels of glucose-regulated protein 78 (0.64 versus 0.26, p = .017), calreticulin (p = .040), and CCAAT/enhancer-binding protein homologous protein (0.95 versus 0.43, p = .047), phosphorylation of protein kinase RNA-like ER kinase (p = .003), and caspase 12 activation (0.30 versus 0.06, p < .001) in myocardium from the SPS rats. The ratio of Bcl-2 to Bax decreased significantly in myocardium from the SPS rats (p = .005). CONCLUSIONS: The ERS-related apoptosis mediated by the protein kinase RNA-like ER kinase/CCAAT/enhancer-binding protein-homologous protein and caspase 12 pathways may be associated with myocardial injury in a rat model simulating PTSD. This study may advance our understanding of how PTSD contributes to myocardial injury on a molecular level. PMID- 27359175 TI - Perceived Ethnic Discrimination and the Metabolic Syndrome in Ethnic Minority Groups: The Healthy Life in an Urban Setting Study. AB - OBJECTIVE: Ethnic differences in the metabolic syndrome could be explained by perceived ethnic discrimination (PED). It is unclear whether PED is associated with the metabolic syndrome. We assessed this association and quantified the contribution of PED to the metabolic syndrome. METHODS: Baseline data were used from the Healthy Life in an Urban Setting study collected in the Netherlands from 2011 to 2014. The population-based sample included South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, and Moroccan participants (aged 18 to 70 years). PED was measured using the Everyday Discrimination Scale. The metabolic syndrome was determined according to the harmonized definition of the International Diabetes Federation, American Heart Association, and others. Logistic regression was used for analysis. population-attributable fraction was used to calculate the contribution of PED. RESULTS: PED was positively associated with the metabolic syndrome in South-Asian Surinamese, African Surinamese, and Moroccan participants (odds ratio [95% confidence interval] = 1.13 [0.99-1.30], 1.15 [1.00-1.32], and 1.19 [1.03-1.38], respectively) after adjusting for potential confounders and mediators. No significant association was observed among Ghanaian and Turkish participants. For the individual components, the associations were statistically significant for blood pressure, fasting glucose, and waist circumference among Surinamese participants. PED was associated with dyslipidemia in Moroccan participants. The population-attributable fractions were 5% for South-Asian Surinamese and Moroccan participants, and 7% for African Surinamese participants. CONCLUSIONS: We found a positive association of PED with the metabolic syndrome in some ethnic groups, with PED contributing around 5% to 7% to the metabolic syndrome among Surinamese and Moroccans. This suggests that PED might contribute to ethnic differences in the metabolic syndrome. PMID- 27359174 TI - The Association Between Psychiatric Disorders and Telomere Length: A Meta Analysis Involving 14,827 Persons. AB - OBJECTIVE: This study examined the relationship between leukocyte telomere length (LTL), a marker of cell aging, and psychiatric disorders in adults compared with controls using meta-analytic methods. METHODS: Data were abstracted from studies examining the relationship between LTL and adult psychiatric disorders. In addition to an overall estimate of effect size, subgroup analyses and meta regression were performed to examine whether covariates (including psychiatric diagnoses) moderated the estimate. RESULTS: A significant overall effect size showing LTL shortening was found across all psychiatric disorders (Hedge g = 0.50, p < .001). Subgroup analyses did not demonstrate significant differences in effect size based on individual covariates (psychiatric disorder, sex, age, or assay method). The meta-regression indicated that although type of disorder and, likely, age moderate the overall effect size, the heterogeneity between studies could not be explained by a model that included these variables as well as sex and assay method. Although not significantly different, posttraumatic stress disorder, anxiety disorders, and depressive disorders had comparatively larger effect sizes (-1.27, -0.53, and -0.55), and psychotic and bipolar disorders had comparatively smaller ones (-0.23 and -0.26). CONCLUSIONS: We observed a robust effect size of LTL shortening for psychiatric disorders as a whole compared with controls. The results were less straightforward regarding relative differences in the strength of this association by specific disorder. Future studies should focus on mechanisms explaining accelerated cell aging with psychiatric illness, defining directions (if any) of causality and elucidating possible differences in this association between disorders. PMID- 27359176 TI - Effects of a Multicomponent Life-Style Intervention on Weight, Glycemic Control, Depressive Symptoms, and Renal Function in Low-Income, Minority Patients With Type 2 Diabetes: Results of the Community Approach to Lifestyle Modification for Diabetes Randomized Controlled Trial. AB - OBJECTIVE: Few interventions have combined life-style and psychosocial approaches in the context of Type 2 diabetes management. The purpose of this study was to determine the effect of a multicomponent behavioral intervention on weight, glycemic control, renal function, and depressive symptoms in a sample of overweight/obese adults with Type 2 diabetes and marked depressive symptoms. METHODS: A sample of 111 adults with Type 2 diabetes were randomly assigned to a 1-year intervention (n = 57) or usual care (n = 54) in a parallel groups design. Primary outcomes included weight, glycosylated hemoglobin, and Beck Depression Inventory II score. Estimated glomerular filtration rate served as a secondary outcome. All measures were assessed at baseline and 6 and 12 months after randomization by assessors blind to randomization. Latent growth modeling was used to examine intervention effects on each outcome. RESULTS: The intervention resulted in decreased weight (mean [M] = 0.322 kg, standard error [SE] = 0.124 kg, p = .010) and glycosylated hemoglobin (M = 0.066%, SE = 0.028%, p = .017), and Beck Depression Inventory II scores (M = 1.009, SE = 0.226, p < .001), and improved estimated glomerular filtration rate (M = 0.742 ml.min.1.73 m, SE = 0.318 ml.min.1.73 m, p = .020) each month during the first 6 months relative to usual care. CONCLUSIONS: Multicomponent behavioral interventions targeting weight loss and depressive symptoms as well as diet and physical activity are efficacious in the management of Type 2 diabetes. TRIAL REGISTRATION: This study is registered at Clinicaltrials.gov ID: NCT01739205. PMID- 27359177 TI - The Role of Occupational Status in the Association Between Job Strain and Ambulatory Blood Pressure During Working and Nonworking Days. AB - OBJECTIVES: The objectives of this study were to determine whether job strain is more strongly associated with higher ambulatory blood pressure (ABP) among blue collar workers compared with white-collar workers, to examine whether this pattern generalizes across working and nonworking days and across sex, and to examine whether this pattern is accounted for by psychosocial factors or health behaviors during daily life. METHODS: A total of 480 healthy workers (mean age = 43 years, 53% female) in the Adult Health and Behavior Project-Phase 2 completed ABP monitoring during 3 working days and 1 nonworking day. Job strain was operationalized as high psychological demand (> sample median) combined with low decision latitude ( 3.00, p < .01). Importantly, the differences in memory specificity were independent of depressive symptoms and trait rumination. CONCLUSIONS: The present study extends findings on rAMS to a previously unstudied sample of patients with SSD. Importantly, the presence of rAMS could not be explained by increased levels of depressive symptoms and rumination. We submit that rAMS in this group reflects how health-related episodes and associated symptoms are encoded in memory. PMID- 27359182 TI - Effects of a Home-Based DVD-Delivered Physical Activity Program on Self-Esteem in Older Adults: Results From a Randomized Controlled Trial. AB - OBJECTIVE: Although center-based supervised physical activity interventions have proved to be successful in attenuating health declines in older adults, such methods can be costly and have limited reach. In the present study, we examined the effects of a DVD-delivered exercise intervention on self-esteem and its subdomains and the extent to which these effects were maintained. In addition, we examined whether psychological, demographic, and biological factors acted as determinants of self-esteem. METHODS: Low-active, older adults (n = 307; mean [standard deviation] age =71.0 [5.1] years) were randomly assigned to a 6-month, home-based exercise program consisting of a DVD-delivered exercise intervention focused on increasing flexibility, toning, and balance (FlexToBa) or an attentional control DVD condition focused on healthy aging. Physical self-worth and three subdomains of self-esteem, global self-esteem, and self-efficacy were assessed at baseline, 6 months, and 12 months. RESULTS: There was a differential effect of time for the two groups for physical self-worth (F interaction(2,530.10) = 4.17, p = .016) and perception of physical condition (F interaction(1,630.77) = 8.31, p = .004). Self-efficacy, sex, body mass index, and age were significant predictors of changes in physical self-worth and perception of physical condition. CONCLUSION: Our findings suggest that a DVD-delivered exercise intervention is efficacious for improving and maintaining subdomain and domain levels of self-esteem in older adults. In addition, self-efficacy was the strongest predictor of changes in physical self-worth and perceptions of physical condition. This innovative method of delivering an exercise training program via DVD is practical and effective and has the potential for broad reach and dissemination. TRIAL REGISTRATION: Clinicaltrials.govidentifier:NCT01030419. PMID- 27359183 TI - Measures of Heart Rate Variability in Individuals With Somatic Symptom Disorder. AB - OBJECTIVE: Little is known about autonomic nervous system activity in individuals with somatic symptom disorder (SSD) as defined by DSM-V criteria. The aims of this study were to investigate whether individuals with SSD differ from healthy controls in heart rate variability (HRV) measures of autonomic nervous system activity and whether sex has a moderating effect on this association. METHODS: We recruited 168 individuals with SSD (35.1% men) and 106 healthy controls (27.4% men). Demographics, HRV, and psychological factors were measured using the Patient Health Questionnaire-15, Health Anxiety Questionnaire, Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory. Multiple regression analysis was used to examine the association of SSD with HRV, adjusting for demographic and psychological measures. RESULTS: Individuals with SSD had lower levels of total-power HRV and low-frequency HRV, but no differences in high-frequency (HF) HRV were found. HRV differences between SSD and controls varied by sex and age (triple interaction TP-HRV beta = -0.222, p < .001; low-frequency HRV beta = 0.332, p < .001; and HF-HRV beta = -0.167, p = .006). Whole-sample multiple regression analyses revealed significant sex differences in the magnitudes of the association between BDI-II with HF-HRV (beta of sex*BDI-II: 0.761, p = .005) and analyses stratified by sex indicated that HF-HRV was significantly correlated with depression in men with SSD (r = -0.491, p < .001) but not in women with SSD (r = 0.057, p = .558). CONCLUSIONS: These results suggest that patients with SSD demonstrate different patterns of HRV and the patterns of association between HRV indices and psychological factors vary between men and women. PMID- 27359185 TI - The ICSD-3 and DSM-5 guidelines for diagnosing narcolepsy: clinical relevance and practicality. AB - Narcolepsy is a chronic neurological disease manifesting as difficulty with maintaining continuous wake and sleep. Clinical presentation varies but requires excessive daytime sleepiness (EDS) occurring alone or together with features of rapid-eye movement (REM) sleep dissociation (e.g., cataplexy, hypnagogic/hypnopompic hallucinations, sleep paralysis), and disrupted nighttime sleep. Narcolepsy with cataplexy is associated with reductions of cerebrospinal fluid (CSF) hypocretin due to destruction of hypocretin peptide-producing neurons in the hypothalamus in individuals with a specific genetic predisposition. Updated diagnostic criteria include the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) and International Classification of Sleep Disorders Third Edition (ICSD-3). DSM-5 criteria require EDS in association with any one of the following: (1) cataplexy; (2) CSF hypocretin deficiency; (3) REM sleep latency <=15 minutes on nocturnal polysomnography (PSG); or (4) mean sleep latency <=8 minutes on multiple sleep latency testing (MSLT) with >=2 sleep-onset REM-sleep periods (SOREMPs). ICSD-3 relies more upon objective data in addition to EDS, somewhat complicating the diagnostic criteria: 1) cataplexy and either positive MSLT/PSG findings or CSF hypocretin deficiency; (2) MSLT criteria similar to DSM-5 except that a SOREMP on PSG may count as one of the SOREMPs required on MSLT; and (3) distinct division of narcolepsy into type 1, which requires the presence of cataplexy or documented CSF hypocretin deficiency, and type 2, where cataplexy is absent, and CSF hypocretin levels are either normal or undocumented. We discuss limitations of these criteria such as variability in clinical presentation of cataplexy, particularly when cataplexy may be ambiguous, as well as by age; multiple and/or invasive CSF diagnostic test requirements; and lack of normative diagnostic test data (e.g., MSLT) in certain populations. While ICSD-3 criteria reflect narcolepsy pathophysiology, DSM-5 criteria have greater clinical practicality, suggesting that valid and reliable biomarkers to help standardize narcolepsy diagnosis would be welcomed. PMID- 27359184 TI - Positive Self-Perceptions of Aging and Lower Rate of Overnight Hospitalization in the US Population Over Age 50. AB - OBJECTIVE: The aging of the baby boomer generation has led to an unprecedented rise in the number of US adults reaching old age, prompting an urgent call for innovative and cost-effective ways to address the increasing health care needs of the aging population. Studying the role of psychosocial factors on health care use could offer insight into how to minimize hospitalizations among older adults. METHODS: We use prospective data from a subsample of 4735 participants (mean [standard deviation] age = 69 [8.79] years, 61% women) from the Health and Retirement Study, a nationally representative study of US adults over age 50, to examine the association between self-perceptions of aging (SPA) and self-reported overnight hospitalizations after adjusting for a comprehensive list of sociodemographic, health-related, and behavioral factors. RESULTS: Over the 4 year follow-up period, there were a total of 5196 overnight hospitalizations, and 44% of the sample reported being hospitalized overnight at least once. After adjusting for sociodemographic factors, each standard deviation increase in positive SPA was associated with a lower rate of overnight hospitalization (incidence rate ratio = 0.75; 95% confidence interval = 0.71-0.80, p < .001). After dividing respondents into quartiles of SPA, we observed a dose-response relationship with individuals in higher quartiles showing increasingly lower rates of overnight hospitalization. CONCLUSIONS: Positive self-perceptions of aging are associated with a lower rate of hospitalization among older adults over a 4-year period. Future research should examine the factors that contribute to older adults' SPA and explore the pathways through which attitudes toward aging influence the use of health care resources. PMID- 27359186 TI - Obstructive sleep apnea hypopnea syndrome was a risk factor for uncontrolled hypertension in adult snorers in South China. AB - BACKGROUND: The association of obstructive sleep apnea hypopnea syndrome (OSAHS) with uncontrolled hypertension has not been fully investigated to date. The present article will investigate the associated factors of uncontrolled hypertension in South China Method: A total of 668 patients (531 males, 137 females) in South China were enrolled in this study. All patients completed questionnaires and then underwent an in-hospital polysomnography. RESULT: Univariate analysis showed that drinking, apnea-hypopnea index, Epworth Sleepiness Scale (ESS) index, the presence of OSAHS, MSaO2 and the lowest SaO2, circumference of neck and waist were predictors of uncontrolled hypertension. Multiple logistic regression analysis showed that ESS, presence of OSAHS, and the lowest SaO2 was independently associated with the risk for uncontrolled hypertension. CONCLUSION: The lowest SaO2, ESS index, and OSAHS were risk factors for uncontrolled hypertension. PMID- 27359187 TI - miRNAs: mediators of ErbB family targeted therapy resistance. AB - The ErbB/HER tyrosine kinase receptors family plays a key regulatory role in different cellular processes by activating several signaling pathways. In different tumor types, mutations or overexpression of the ErbB family members are a common feature, which led to the development of targeted therapies against this receptors. Although with this kind of treatment we are heading to a more personalized medicine, the development of acquired resistance is still an issue, therefore, several studies focused on discovering the mechanisms behind it. More recently, miRNAs have been described as important mediators of acquired resistance, specifically, acquired resistance to ErbB family targeted therapies. Ultimately, miRNA-based therapeutics using exosomes as a drug delivery model can revolutionize today's approach of cancer treatment. PMID- 27359188 TI - Orofacial Contracture Management: Current Patterns of Clinical Practice in Australian and New Zealand Adult Burn Units. AB - Burn injury to the face can lead to scarring and contractures that may impair oral competence for articulation, feeding, airway intubation access, oral/dental hygiene, aesthetics, and facial expression. Although a range of therapy interventions has been discussed for preventing contracture formation, there is minimal information on current practice patterns. This research examined patterns of clinical practice for orofacial burns management during a 4-year period to determine the nature and extent of clinical consistency in current care. Allied health clinicians involved in orofacial contracture management in Australia and New Zealand were surveyed at two time points (2010 and 2014). Twenty and 23 clinicians, respectively, across a range of allied health professions completed the surveys. Both surveys revealed multiple allied health disciplines, predominantly occupational therapy, speech language pathology, and physiotherapy, were involved orofacial burn management. A high degree of variation was observed across clinical practices in the 2010 survey. In the 2014 survey, although, greater consistency in practice patterns was observed with more clinicians commencing intervention earlier, with greater treatment intensity observed and more treatment modalities being used. Furthermore, in 2014, there was an increased use of assessment tools and clinical indicators to guide patient treatment. Agreement regarding clinical practice pathways for orofacial contracture rehabilitation is still emerging, and treatment continues to be predominantly guided by clinical experience. There is an urgent need for treatment efficacy research utilizing validated outcome measure tools to inform clinical consensus and practice guidelines. PMID- 27359189 TI - Burn Rehabilitation Therapists Competency Tool-Version 2: An Expansion to Include Long-Term Rehabilitation and Outpatient Care. AB - The Burn Rehabilitation Therapist Competency Tool (BRTCT) was developed in 2011 to define core knowledge and skill sets that are central to the job performance of occupational and physical therapists working with burn patients during acute hospitalization and initial rehabilitation. It was the first national effort to provide standards that burn centers could use for the training and evaluation of a BRT performance. The American Burn Association Rehabilitation Committee recently expanded the tool to include long-term rehabilitation and outpatient care in order to more fully represent all of the stages of care in which patients with burn injury receive therapy. Thirty-six burn centers contributed competencies, 17 rehabilitation experts participated in a systematic Delphi questionnaire process, and eight representatives from seven additional burn centers validated the tool. The revised BRTCT, called the BRTCT-2, includes four new practice domains and 28 new competency statements. The expanded tool provides a common framework of standards for performance for occupational and physical therapists working with patients throughout the full spectrum of burn care. PMID- 27359190 TI - Post Junctional Sudomotor and Cutaneous Vascular Responses in Noninjured Skin Following Heat Acclimation in Burn Survivors. AB - Thermal tolerance is improved in burn survivors following 7 days of exercise heat acclimation. It is unknown whether post junctional sudomotor and/or cutaneous vascular adaptations in noninjured skin contribute to this improvement. Thirty three burn survivors were stratified into moderately (17-40% BSA grafted, n = 19) and highly (>40% BSA grafted, n = 14) skin-grafted groups. Nine nonburned subjects served as controls. All subjects underwent a 7-day heat acclimation protocol, which improved thermal tolerance in all groups. Before and after this heat acclimation protocol, post junctional cutaneous vascular responses were assessed by administering increasing doses of sodium nitroprusside (SNP) and methacholine (MCh) using intradermal microdialysis in noninjured skin. MCh infusion was also used to assess post junctional responses in sudomotor function in noninjured skin. Cutaneous vascular responses to SNP and MCh were not different between pre- and post heat acclimation in either group of burn survivors (both P > .05). The maximal sweating rate to MCh increased post acclimation in the control group (0.41 +/- 0.20 to 0.54 +/- 0.21 mg.min.cm; P = .016) but was unchanged in both groups of burn survivors (both P > .05). The number of sweat glands activated during the highest dose of MCh was elevated in the >40% BSA-grafted group (49 +/- 16 to 56 +/- 18 glands.cm; P = .005) but was unchanged in control subjects and the <40% BSA-grafted group (both P > .05). Given that post junctional administration of MCh and SNP did not alter sweating or skin blood flow from noninjured skin of burn survivors, improved thermal tolerance in these individuals following heat acclimation is more likely a result of either an increased sweating efficiency or an increased neural drive for sweating. PMID- 27359191 TI - Review of Adult Electrical Burn Injury Outcomes Worldwide: An Analysis of Low Voltage vs High-Voltage Electrical Injury. AB - The aims of this article are to review low-voltage vs high-voltage electrical burn complications in adults and to identify novel areas that are not recognized to improve outcomes. An extensive literature search on electrical burn injuries was performed using OVID MEDLINE, PubMed, and EMBASE databases from 1946 to 2015. Studies relating to outcomes of electrical injury in the adult population (>=18 years of age) were included in the study. Forty-one single-institution publications with a total of 5485 electrical injury patients were identified and included in the present study. Fourty-four percent of these patients were low voltage injuries (LVIs), 38.3% high-voltage injuries (HVIs), and 43.7% with voltage not otherwise specified. Forty-four percentage of studies did not characterize outcomes according to LHIs vs HVIs. Reported outcomes include surgical, medical, posttraumatic, and others (long term/psychological/rehabilitative), all of which report greater incidence rates in HVI than in LVI. Only two studies report on psychological outcomes such as posttraumatic stress disorder. Mortality rates from electrical injuries are 2.6% in LVI, 5.2% in HVI, and 3.7% in not otherwise specified. Coroner's reports revealed a ratio of 2.4:1 for deaths caused by LVI compared with HVI. HVIs lead to greater morbidity and mortality than LVIs. However, the results of the coroner's reports suggest that immediate mortality from LVI may be underestimated. Furthermore, on the basis of this analysis, we conclude that the majority of studies report electrical injury outcomes; however, the majority of them do not analyze complications by low vs high voltage and often lack long-term psychological and rehabilitation outcomes after electrical injury indicating that a variety of central aspects are not being evaluated or assessed. PMID- 27359196 TI - Mg(PF6)2-Based Electrolyte Systems: Understanding Electrolyte-Electrode Interactions for the Development of Mg-Ion Batteries. AB - Mg(PF6)2-based electrolytes for Mg-ion batteries have not received the same attention as the analogous LiPF6-based electrolytes used in most Li-ion cells owing to the perception that the PF6(-) anion decomposes on and passivates Mg electrodes. No synthesis of the Mg(PF6)2 salt has been reported, nor have its solutions been studied electrochemically. Here, we report the synthesis of the complex Mg(PF6)2(CH3CN)6 and its solution-state electrochemistry. Solutions of Mg(PF6)2(CH3CN)6 in CH3CN and CH3CN/THF mixtures exhibit high conductivities (up to 28 mS.cm(-1)) and electrochemical stability up to at least 4 V vs Mg on Al electrodes. Contrary to established perceptions, Mg electrodes are observed to remain electrochemically active when cycled in the presence of these Mg(PF6)2 based electrolytes, with no fluoride (i.e., MgF2) formed on the Mg surface. Stainless steel electrodes are found to corrode when cycled in the presence of Mg(PF6)2 solutions, but Al electrodes are passivated. The electrolytes have been used in a prototype Mg battery with a Mg anode and Chevrel (Mo3S4)-phase cathode. PMID- 27359192 TI - Posttraumatic Stress Disorder Diagnosis in Young Children With Burns. AB - The primary aim of this study was to assess the prevalence of posttraumatic stress disorder (PTSD) in young children hospitalized for burns. A secondary aim was to assess partial PTSD in this population. PTSD diagnosis and symptoms were evaluated utilizing both the diagnostic interview for children and adolescents (DICA-P) module and the PTSD semistructured interview and observational report (PTSDSSI). PTSD symptomatology was assessed from parent interviews at 1 month after discharge from a major pediatric burn center. Four of the 42 participants who completed the DICA-P met full criteria for a diagnosis of PTSD (10%).Of the 39 who also completed the PTSDSSI, 1 (3%) met full criteria for PTSD diagnosis on that measure. Twenty-seven percentage of subjects met partial criteria on the DICA-P vs 16% on the PTSDSSI, without impairment. Furthermore, 67% of subjects met DICA-P criteria for the re-experiencing cluster and 54% met the PTSDSSI re experiencing criteria. Although only a small percentage met full PTSD diagnostic criteria by either measure, a high percentage of young children with burns manifested some posttraumatic symptoms 1 month after discharge. Because PTSDSSI diagnosis is strongly linked to the diagnostic and statistical manual-5 (DSM-5) criteria for "PTSD in children 6 years and younger," these results may offer clues to current diagnoses of PTSD in young children. Future research is needed to improve care by determining the risk factors and course of PTSD to further refine the diagnostic criteria for identifying children most in need of intervention, such as those hospitalized for burn injuries. PMID- 27359197 TI - Patch Splinting for Atrophic or Tight Skin Excision Wounds. PMID- 27359198 TI - Bloodroot Paste: What Dermatologists and Patients Need to Know. PMID- 27359199 TI - Ablative Fractional Laser-Assisted Topical Fluorouracil for the Treatment of Superficial Basal Cell Carcinoma and Squamous Cell Carcinoma In Situ: A Follow-Up Study. AB - BACKGROUND: The authors previously reported the safety and short-term efficacy of ablative fractional laser (AFXL)-assisted delivery of topical fluorouracil in the treatment of superficial basal cell carcinoma (sBCC) and squamous cell carcinoma in situ (SCCis). OBJECTIVE: This follow-up study was conducted to assess whether tumor clearance was sustained in this cohort of patients at >9 months post treatment. METHODS: Thirty primary sBCC or SCCis <2 cm on the trunk or extremities were treated with AFXL and a single application of topical 5 fluorouracil 5% under occlusion for 7 days. Among the 26 patients who achieved tumor clearance at 4 to 8 weeks post-treatment, 20 patients presented for this follow-up study and underwent shave biopsy to confirm histologic clearance. Mean follow-up time was 15 months. RESULTS: Considering those who had persistent tumor at 4 to 8 weeks post-treatment and those who presented for follow-up at >9 months post-treatment, overall treatment success was 79% (95% confidence interval: 67% 96%), with 92% (11/12) for SCCis and 67% (8/12) for sBCC. Neither the tumor location nor size significantly impacted treatment outcome (p = .96 and 0.87, respectively). CONCLUSION: Ablative fractional laser-assisted topical fluorouracil is a reasonable noninvasive treatment option for primary SCCis and sBCC, especially for lesions located in areas where self-application is not possible, or when clinician-administered therapy is preferred. PMID- 27359200 TI - Mycobacterium Massiliense Infection After Thread-Lift Insertion. PMID- 27359202 TI - Hierarchical Mesoporous Lithium-Rich Li[Li0.2Ni0.2Mn0.6]O2 Cathode Material Synthesized via Ice Templating for Lithium-Ion Battery. AB - Tuning hierarchical micro/nanostructure of electrode materials is a sought-after means to reinforce their electrochemical performance in the energy storage field. Herein, we introduce a type of hierarchical mesoporous Li[Li0.2Ni0.2Mn0.6]O2 microsphere composed of nanoparticles synthesized via an ice templating combined coprecipitation strategy. It is a low-cost, eco-friendly, and easily operated method using ice as a template to control material with homogeneous morphology and rich porous channels. The as-prepared material exhibits remarkably enhanced electrochemical performances with higher capacity, more excellent cycling stability and more superior rate property, compared with the sample prepared by conventional coprecipitation method. It has satisfactory initial discharge capacities of 280.1 mAh g(-1) at 0.1 C, 207.1 mAh g(-1) at 2 C, and 152.4 mAh g( 1) at 5 C, as well as good cycle performance. The enhanced electrochemical performance can be ascribed to the stable hierarchical microsized structure and the improved lithium-ion diffusion kinetics from the highly porous structure. PMID- 27359203 TI - Drinking pattern of wine and effects on human health: why should we drink moderately and with meals? AB - Conclusions of epidemiological studies examining the effects of alcoholic beverages on human health may be unclear and limited if they do not take into account drinking pattern parameters such as beverage type, regular moderate versus binge drinking and drinking with or without meals. This review considers different aspects of drinking patterns and effects on human health with special attention to wine. We particularly discuss the potential underlying mechanisms for epidemiological evidence that the beneficial effects of wine are more evident if consumed with food. In this context, we address the effects of food on blood alcohol concentration and acetaldehyde production in the gastrointestinal tract, the role of wine components and uric acid in counteracting the detrimental effects of postprandial oxidative stress, as well as wine's antimicrobial properties and its potential to act as a digestive aid. In addition to its biological correlates, drinking patterns with regard to different socio-cultural circumstances in different populations are also considered. In order to avoid confusion and misconceptions in the general population because of the hormetic associations of wine with human health, it is important that all medical and scientific information concerning the effect of wine consumption on human health are evidence-based and communicated in a competent, credible and unbiased manner. In conclusion, we propose several practical recommendations concerning wine consumption and consumer information to minimize the risks of alcohol-related harm and to encourage individual responsibility and a healthy lifestyle. PMID- 27359204 TI - Upper-Extremity Explosive Resistance Training With Older Adults Can Be Regulated Using the Rating of Perceived Exertion. AB - Row Lazzarini, BR, Dropp, M, and Lloyd, W. Upper-extremity explosive resistance training with older adults can be regulated using the rating of perceived exertion. J Strength Cond Res 31(3): 831-836, 2017-Explosive resistance training (ERT) improves muscle strength and power in older adults. Previous work has determined that the Borg rating of perceived exertion (RPE) scale can be used to regulate ERT loads for older adults on the leg press exercise. The purpose of this study was to assess the relationship between the Borg RPE scale and ERT loads relative to the 1 repetition maximum (%1RM) in older adults during the chest press exercise. Healthy seniors (n = 10 men, mean [SD] age 75.8 [7.9]; n = 10 women, age 73.0 [6.3]) took part in 2 sessions on nonconsecutive days. During the first session, subjects reported their RPE during multiple ERT repetitions on the chest press for 7 loads across the spectrum of "light" to "heavy", ranging from 20 to 105% body weight. The loads, concealed from the participants, were presented in randomized order. During the second session, a 1RM strength test was conducted. Each load experienced on the first visit was calculated as %1RM. Rating of perceived exertion was averaged across subjects for each 5% range of 1RM from 35% 1RM to 110% 1RM. Regression analysis was used to determine if RPE predicts %1RM during chest press ERT. Rating of perceived exertion predicted the %1RM corresponding with chest press ERT loads (R = 97.6%, SEE 3.6, p < 0.001). Loads that would elicit both strength and power gains (70-90% 1RM) corresponded with an RPE of 14-17. As previously demonstrated with the leg press, ERT loads can be regulated for older adults during the chest press using RPE, allowing ERT to be conducted without maximal strength testing. This approach may increase the adoption of this training method for a broader spectrum of seniors. PMID- 27359205 TI - Identifying Dosage Effect of Light-Emitting Diode Therapy on Muscular Fatigue in Quadriceps. AB - Hemmings, TJ, Kendall, KL, and Dobson, JL. Identifying dosage effect of light emitting diode therapy on muscular fatigue in quadriceps. J Strength Cond Res 31(2): 395-402, 2017-The purpose of this study was to compare the effects of various dosages of light-emitting diode therapy (LEDT) on muscle fatigue while performing a single-leg extension to exhaustion. A total of 34 recreationally resistance-trained athletes between the ages of 18 and 26 participated in 4 trials. Each trial included pre-exercise/postexercise blood lactate measurements and 2 sets of 3 maximal voluntary isometric contractions (MVICs), followed by LEDT on 6 points across the superficial quadriceps. Each randomized trial consisted of a placebo, 30, 60, or 120 seconds on each point on the quadriceps. Three minutes after LEDT, the participants performed an eccentric leg extension with 120% of MVIC until fatigue. There was significant increase in the number of repetitions performed between the placebo treatment and 60 seconds (p = 0.023), as well as placebo and 120 seconds (p = 0.004) of irradiation on each point. There were no significant differences in blood lactate levels between any of the 4 trials. In conclusion, LEDT had a positive effect on performance when irradiating 6 points on the superficial quadriceps for 60 and 120 seconds before an eccentric leg extension. PMID- 27359206 TI - Activity Profile and Between-Match Variation in Elite Male Field Hockey. AB - Sunderland, CD and Edwards, PL. Activity profile and between-match variation in elite male field hockey. J Strength Cond Res 31(3): 758-764, 2017-This study aimed to (a) provide a position-specific activity profile for elite male hockey players, (b) determine if the activity profile was altered by the introduction of the "self-pass" rule, and (c) provide information relating to match-to-match variability in elite male field hockey. The activity of 28 elite male field hockey players was analyzed over 2 seasons totaling 395 player-match analyses using Global Positioning Satellite technology. Total distance, high-speed running (>15.5 km.h), sprinting (>20 km.h), and mean speed were recorded. Players were categorized into 4 positions: fullback (FB), halfback (HB), midfield (M), and forward (F). Data were analyzed using a 2-way analysis of variance (season, position) and between-match coefficients of variation (CV). The time played differs with position (FB: 65.5 +/- 5.3, HB: 49.5 +/- 11.5, M: 45.9 +/- 7.1, F: 39.5 +/- 5.4 minutes; p < 0.0005) and thus affected the activity profile. Total distance covered was greater for fullbacks (FB: 8,001 +/- 447, HB: 6,435 +/- 1,399, M: 6,415 +/- 908, F: 5,844 +/- 762 m, p < 0.001), and mean speed and percentage time spent high-speed running and sprinting were greater for forwards than all other positions (HSR: FB: 6.8 +/- 1.0, HB: 8.8 +/- 1.3, M: 10.7 +/- 1.2, F: 13.5 +/- 1.8%, p < 0.001). The activity profile did not differ with the introduction of the self-pass. Match-to-match variability (CV) ranged from 5.0% to 22.0% for total and sprint distance, respectively. This is the first study to present an activity profile of elite men's field hockey and its associated variability and demonstrates that each position is unique, and therefore, training and recovery should be position specific. PMID- 27359207 TI - Responses of Lower-Body Power and Match Running Demands Following Long-Haul Travel in International Rugby Sevens Players. AB - Mitchell, JA, Pumpa, KL, and Pyne, DB. Responses of lowerbody power and match running demands after long-haul travel in international rugby sevens players. J Strength Cond Res 31(3): 686-695, 2017-This study determined the effect of long haul (>5 hours) travel on lower-body power and match running demands in international rugby sevens players. Lower-body power was assessed in 22 male international rugby sevens players (age 21.7 +/- 2.7 years, mass 89.0 +/- 6.7 kg, stature 180.5 +/- 6.2 cm; mean +/- SD) monitored over 17 rugby sevens tournaments. A countermovement jump was used to monitor lower-body power (peak and mean power) over repeated three week travel and competition periods (pretravel, posttravel, and posttournament). Small decreases were evident in peak power after both short and long-haul travel (-4.0%, +/-3.2%; mean, +/-90% confidence limits) with further reductions in peak and mean power posttournament (-4.5%, +/-2.3% and -3.8%, +/-1.5%) culminating in a moderate decrease in peak power overall (-7.4%, +/-4.0%). A subset of 12 players (completing a minimum of 8 tournaments) had the effects of match running demands assessed with lower-body power. In this subset, long-haul travel elicited a large decrease in lower-body peak (-9.4%, +/-3.5%) and mean power (-5.6%, +/-2.9%) over the monitoring period, with a small decrease (-4.3%, +/-3.0% and -2.2%, +/-1.7%) posttravel and moderate decrease (-5.4%, +/-2.5% and -3.5%, +/-1.9%) posttournament, respectively. Match running demands were monitored through global positioning system. In long-haul tournaments, the 12 players covered ~13%, +/-13% greater total distance (meter) and ~11%, +/-10% higher average game meters >5 m.s when compared with short-haul (<5 hours) travel. Effective pretravel and posttravel player management strategies are indicated to reduce neuromuscular fatigue and running load demands in rugby sevens tournaments after long-haul travel. PMID- 27359208 TI - Power Relative to Body Mass Best Predicts Change in Core Temperature During Exercise-Heat Stress. AB - Gibson, OR, Willmott, AGB, James, CA, Hayes, M, and Maxwell, NS. Power relative to body mass best predicts change in core temperature during exercise-heat stress. J Strength Cond Res 31(2): 403-414, 2017-Controlling internal temperature is crucial when prescribing exercise-heat stress, particularly during interventions designed to induce thermoregulatory adaptations. This study aimed to determine the relationship between the rate of rectal temperature (Trec) increase, and various methods for prescribing exercise-heat stress, to identify the most efficient method of prescribing isothermic heat acclimation (HA) training. Thirty-five men cycled in hot conditions (40 degrees C, 39% R.H.) for 29 +/- 2 minutes. Subjects exercised at 60 +/- 9% V[Combining Dot Above]O2peak, with methods for prescribing exercise retrospectively observed for each participant. Pearson product moment correlations were calculated for each prescriptive variable against the rate of change in Trec ( degrees C.h), with stepwise multiple regressions performed on statistically significant variables (p <= 0.05). Linear regression identified the predicted intensity required to increase Trec by 1.0-2.0 degrees C between 20- and 45-minute periods and the duration taken to increase Trec by 1.5 degrees C in response to incremental intensities to guide prescription. Significant (p <= 0.05) relationships with the rate of change in Trec were observed for prescriptions based on relative power (W.kg; r = 0.764), power (%Powermax; r = 0.679), rating of perceived exertion (RPE) (r = 0.577), V[Combining Dot Above]O2 (%V[Combining Dot Above]O2peak; r = 0.562), heart rate (HR) (%HRmax; r = 0.534), and thermal sensation (r = 0.311). Stepwise multiple regressions observed relative power and RPE as variables to improve the model (r = 0.791), with no improvement after inclusion of any anthropometric variable. Prescription of exercise under heat stress using power (W.kg or %Powermax) has the strongest relationship with the rate of change in Trec with no additional requirement to correct for body composition within a normal range. Practitioners should therefore prescribe exercise intensity using relative power during isothermic HA training to increase Trec efficiently and maximize adaptation. PMID- 27359211 TI - Proprotein convertase subtilisin / kexin 9 (PCSK9) inhibitors and the future of dyslipidemia therapy: an updated patent review (2011-2015). AB - INTRODUCTION: The identification by Abifadel et al. in 2003 of the first mutations of PCSK9 was the major breakthrough in the cholesterol field that led to a new therapeutic target. This discovery paved the way to new lipid lowering drugs reducing LDL-cholesterol levels through the inhibition of PCSK9. Two anti PCSK9 monoclonal antibodies have received FDA and EMA approvals: Alirocumab and Evolocumab. Areas covered: This article reviews the different strategies that are pursued to modulate the functional activity of PCSK9 for lowering LDL-cholesterol levels. It also provides a brief overview of the patents related to PCSK9 from 2011 until the end of 2015. This review is addressed to researchers from academia and pharmaceutical companies who are engaged in PCSK9 research/cholesterol regulation. Readers will gain an up-to-date overview of the different strategies that have been investigated to reduce PCSK9, focusing on anti-PCSK9 monoclonal antibodies and the related clinical trials. Expert opinion: Anti-PCSK9 antibodies are a new class of lipid lowering drugs with promising results in reducing LDL cholesterol. Long-term ongoing studies investigating on a large scale the efficacy and safety of the anti-PCSK9 antibodies and their cardiovascular outcomes are eagerly awaited. PMID- 27359212 TI - Nursing Information Systems Requirements: A Milestone for Patient Outcome and Patient Safety Improvement. AB - Considering the integral role of understanding users' requirements in information system success, this research aimed to determine functional requirements of nursing information systems through a national survey. Delphi technique method was applied to conduct this study through three phases: focus group method modified Delphi technique and classic Delphi technique. A cross-sectional study was conducted to evaluate the proposed requirements within 15 general hospitals in Iran. Forty-three of 76 approved requirements were clinical, and 33 were administrative ones. Nurses' mean agreements for clinical requirements were higher than those of administrative requirements; minimum and maximum means of clinical requirements were 3.3 and 3.88, respectively. Minimum and maximum means of administrative requirements were 3.1 and 3.47, respectively. Research findings indicated that those information system requirements that support nurses in doing tasks including direct care, medicine prescription, patient treatment management, and patient safety have been the target of special attention. As nurses' requirements deal directly with patient outcome and patient safety, nursing information systems requirements should not only address automation but also nurses' tasks and work processes based on work analysis. PMID- 27359210 TI - Galanin Activates G Protein Gated Inwardly Rectifying Potassium Channels and Suppresses Kisspeptin-10 Activation of GnRH Neurons. AB - GnRH neurons are regulated by hypothalamic kisspeptin neurons. Recently, galanin was identified in a subpopulation of kisspeptin neurons. Although the literature thoroughly describes kisspeptin activation of GnRH neurons, little is known about the effects of galanin on GnRH neurons. This study investigated whether galanin could alter kisspeptin signaling to GnRH neurons. GnRH cells maintained in explants, known to display spontaneous calcium oscillations, and a long-lasting calcium response to kisspeptin-10 (kp-10), were used. First, transcripts for galanin receptors (GalRs) were examined. Only GalR1 was found in GnRH neurons. A series of experiments was then performed to determine the action of galanin on kp 10 activated GnRH neurons. Applied after kp-10 activation, galanin 1-16 (Gal1-16) rapidly suppressed kp-10 activation. Applied with kp-10, Gal1-16 prevented kp-10 activation until its removal. To determine the mechanism by which galanin inhibited kp-10 activation of GnRH neurons, Gal1-16 and galanin were applied to spontaneously active GnRH neurons. Both inhibited GnRH neuronal activity, independent of GnRH neuronal inputs. This inhibition was mimicked by a GalR1 agonist but not by GalR2 or GalR2/3 agonists. Although Gal1-16 inhibition relied on Gi/o signaling, it was independent of cAMP levels but sensitive to blockers of G protein-coupled inwardly rectifying potassium channels. A newly developed bioassay for GnRH detection showed Gal1-16 decreased the kp-10-evoked GnRH secretion below detection threshold. Together, this study shows that galanin is a potent regulator of GnRH neurons, possibly acting as a physiological break to kisspeptin excitation. PMID- 27359213 TI - Strolling Toward New Concepts. AB - For more than four decades now, I have been studying how genetic information is transformed into protein-based cellular functions. This has included investigations into the mechanisms supporting cellular localization of proteins, disulfide bond formation, quality control of membranes, and translation. I tried to extract new principles and concepts that are universal among living organisms from our observations of Escherichia coli. While I wanted to distill complex phenomena into basic principles, I also tried not to overlook any serendipitous observations. In the first part of this article, I describe personal experiences during my studies of the Sec pathway, which have centered on the SecY translocon. In the second part, I summarize my views of the recent revival of translation studies, which has given rise to the concept that nonuniform polypeptide chain elongation is relevant for the subsequent fates of newly synthesized proteins. Our studies of a class of regulatory nascent polypeptides advance this concept by showing that the dynamic behaviors of the extraribosomal part of the nascent chain affect the ongoing translation process. Vibrant and regulated molecular interactions involving the ribosome, mRNA, and nascent polypeptidyl-tRNA are based, at least partly, on their autonomously interacting properties. PMID- 27359214 TI - The Power of Asymmetry: Architecture and Assembly of the Gram-Negative Outer Membrane Lipid Bilayer. AB - Determining the chemical composition of biological materials is paramount to the study of natural phenomena. Here, we describe the composition of model gram negative outer membranes, focusing on the predominant assembly, an asymmetrical bilayer of lipid molecules. We also give an overview of lipid biosynthetic pathways and molecular mechanisms that organize this material into the outer membrane bilayer. An emphasis is placed on the potential of these pathways as targets for antibiotic development. We discuss deviations in composition, through bacterial cell surface remodeling, and alternative modalities to the asymmetric lipid bilayer. Outer membrane lipid alterations of current microbiological interest, such as lipid structures found in commensal bacteria, are emphasized. Additionally, outer membrane components could potentially be engineered to develop vaccine platforms. Observations related to composition and assembly of gram-negative outer membranes will continue to generate novel discoveries, broaden biotechnologies, and reveal profound mysteries to compel future research. PMID- 27359215 TI - Xenogeneic Silencing and Its Impact on Bacterial Genomes. AB - The H-NS (heat-stable nucleoid structuring) protein affects both nucleoid compaction and global gene regulation. H-NS appears to act primarily as a silencer of AT-rich genetic material acquired by horizontal gene transfer. As such, it is key in the regulation of most genes involved in virulence and in adaptation to new environmental niches. Here we review recent progress in understanding the biochemistry of H-NS and how xenogeneic silencing affects bacterial evolution. We highlight the strengths and weaknesses of some of the models proposed in H-NS-mediated nucleoprotein complex formation. Based on recent single-molecule studies, we also propose a novel mode of DNA compaction by H-NS termed intrabridging to explain over two decades of observations of the H-NS molecule. PMID- 27359216 TI - Genetic Mapping of Pathogenesis Determinants in Toxoplasma gondii. AB - Toxoplasma gondii is a widespread parasite of warm-blooded vertebrates that also causes opportunistic infections in humans. Rodents are a natural host for asexually replicating forms, whereas cats serve as the definitive host for sexual development. The laboratory mouse provides a model to study pathogenesis. Strains of T. gondii are globally diverse, with more than 16 distinct haplogroups clustered into 6 major clades. Forward genetic analysis of genetic crosses between different lineages has been used to define the molecular basis of acute virulence in the mouse. These studies have identified a family of secretory serine/threonine rhoptry kinases that target innate immune pathways to protect intracellular parasites from destruction. Rhoptry kinases target immunity-related GTPases, a family of immune effectors that is expanded in rodents. Similar forward genetic studies may be useful to define the basis of pathogenesis in other hosts, including humans, where infections of different strains present with variable clinical severity. PMID- 27359218 TI - Protists and the Wild, Wild West of Gene Expression: New Frontiers, Lawlessness, and Misfits. AB - The DNA double helix has been called one of life's most elegant structures, largely because of its universality, simplicity, and symmetry. The expression of information encoded within DNA, however, can be far from simple or symmetric and is sometimes surprisingly variable, convoluted, and wantonly inefficient. Although exceptions to the rules exist in certain model systems, the true extent to which life has stretched the limits of gene expression is made clear by nonmodel systems, particularly protists (microbial eukaryotes). The nuclear and organelle genomes of protists are subject to the most tangled forms of gene expression yet identified. The complicated and extravagant picture of the underlying genetics of eukaryotic microbial life changes how we think about the flow of genetic information and the evolutionary processes shaping it. Here, we discuss the origins, diversity, and growing interest in noncanonical protist gene expression and its relationship to genomic architecture. PMID- 27359219 TI - Development of a Coarse-Grained Model of Chitosan for Predicting Solution Behavior. AB - A new coarse-grained (CG) model of chitosan has been developed for predicting solution behavior as a function of degree of acetylation (DA). A multiscale modeling approach was used to derive the energetic and geometric parameters of this implicit-solvent, CG model from all-atom simulations of chitosan and chitin molecules in explicit water. The model includes representations of both protonated d-glucosamine (GlcN(+)) and N-acetyl-d-glucosamine (GlcNAc) monomers, where each monomer consists of three CG sites. Chitosan molecules of any molecular weight, DA, and monomer sequence can be built using this new CG model. Discontinuous molecular dynamics simulations of chitosan solutions show increased self-assembly in solution with increasing DA and chitosan concentration. The chitosan solutions form larger percolated networks earlier in time as DA and concentration increase, indicating "gel-like" behavior, which qualitatively matches experimental studies of chitosan gel formation. Increasing DA also results in a greater number of monomer-monomer associations, which has been predicted experimentally based on an increase in the storage modulus of chitosan gels with increasing DA. Our model also gives insight into how the monomer sequence affects self-assembly and the frequency of interaction between different pairs of monomers. PMID- 27359217 TI - Kin Recognition in Bacteria. AB - The ability of bacteria to recognize kin provides a means to form social groups. In turn these groups can lead to cooperative behaviors that surpass the ability of the individual. Kin recognition involves specific biochemical interactions between a receptor(s) and an identification molecule(s). Recognition specificity, ensuring that nonkin are excluded and kin are included, is critical and depends on the number of loci and polymorphisms involved. After recognition and biochemical perception, the common ensuing cooperative behaviors include biofilm formation, quorum responses, development, and swarming motility. Although kin recognition is a fundamental mechanism through which cells might interact, microbiologists are only beginning to explore the topic. This review considers both molecular and theoretical aspects of bacterial kin recognition. Consideration is also given to bacterial diversity, genetic relatedness, kin selection theory, and mechanisms of recognition. PMID- 27359220 TI - Cell-cycle compensation coupled with developmental patterning. PMID- 27359221 TI - Ideological reactivity: Political conservatism and brain responsivity to emotional and neutral stimuli. AB - Conservatives are often thought to have a negativity bias-responding more intensely to negative than positive information. Yet, recent research has found that greater endorsement of conservative beliefs follows from both positive and negative emotion inductions. This suggests that the role of affect in political thought may not be restricted to negative valence, and more attention should be given to how conservatives and liberals respond to a wider range of stimulation. In this vein, we examined neural responses to a full range of affective stimuli, allowing us to examine how self-reported ideology moderated these responses. Specifically, we explored the relationship between political orientation and 2 event-related potentials (1 late and 1 early) previously shown to covary with the subjective motivational salience of stimuli-in response to photographs with standardized ratings of arousal and valence. At late time points, conservatives exhibited sustained heightened reactivity, compared with liberals, specifically in response to relatively unarousing and neutral stimuli. At early time points, conservatives exhibited somewhat enhanced neural activity in response to all stimulus types compared with liberals. These results may suggest that conservatives experience a wide variety of stimuli in their environment with increased motivational salience, including positive, neutral, and low-arousal stimuli. No effects of valence were found in this investigation. Such findings have implications for the development and refinement of psychological conceptions of political orientation. (PsycINFO Database Record PMID- 27359222 TI - Recognition thresholds for static and dynamic emotional faces. AB - We investigated the minimum expressive intensity that is required to recognize (above chance) static and dynamic facial expressions of happiness, sadness, anger, disgust, fear, and surprise. To this end, we varied the degree of intensity of emotional expressions unfolding from a neutral face, by means of graphics morphing software. The resulting face stimuli (photographs and short videos) were presented in an expression categorization task for 1 s each, and measures of sensitivity or discrimination (A') were collected to establish thresholds. A number of physical, perceptual, categorical, and affective controls were performed. All six basic emotions were reliably recognized above chance level from low intensities, although recognition thresholds varied for different expressions: 20% of intensity, for happiness; 40%, for sadness, surprise, anger, and disgust; and 50%, for fear. The advantage of happy faces may be due to their greater physical change in facial features (as shown by automated facial expression measurement), also at low levels of intensity, relative to neutral faces. Recognition thresholds and the pattern of confusions across expressions were, nevertheless, equivalent for dynamic and static expressions, although dynamic expressions were recognized more accurately and faster. (PsycINFO Database Record PMID- 27359224 TI - One model fits all: Explaining many aspects of number comparison within a single coherent model-A random walk account. AB - The time required to determine the larger of 2 digits decreases with their numerical distance, and, for a given distance, increases with their magnitude (Moyer & Landauer, 1967). One detailed quantitative framework to account for these effects is provided by random walk models. These chronometric models describe how number-related noisy partial evidence is accumulated over time; they assume that the drift rate of this stochastic process varies lawfully with the numerical magnitude of the digits presented. In a complete paired number comparison design we obtained saccadic choice responses of 43 participants, and analyzed mean saccadic latency, error rate, and the standard deviation of saccadic latency for each of the 72 digit pairs; we also obtained mean error latency for each numerical distance. Using only a small set of meaningfully interpretable parameters, we describe a variant of random walk models that accounts in considerable quantitative detail for many facets of our data, including previously untested aspects of latency standard deviation and error latencies. However, different from standard assumptions often made in random walk models, this account required that the distributions of step sizes of the induced random walks are asymmetric. We discuss how our findings can help in interpreting complex findings (e.g., conflicting speed vs. accuracy trends) in applied studies which use number comparison as a well-established diagnostic tool. Finally, we also describe a novel effect in number comparison, the decrease of saccadic response amplitude with numerical distance, and suggest an interpretation using the conceptual framework of random walk models. (PsycINFO Database Record PMID- 27359223 TI - Endovascular Treatment in Patients with Persistent Internal Carotid Artery Occlusion after Intravenous Tissue Plasminogen Activator: A Clinical Effectiveness Study. AB - BACKGROUND: There has been no large-scale trial comparing endovascular treatment (add-on EVT) after intravenous tissue plasminogen activator (IV tPA) and IV tPA alone in acute ischemic stroke (AIS) caused by internal carotid artery occlusion (ICAO). We aimed at investigating the effectiveness and safety of add-on EVT after IV tPA in AIS patients with ICAO. METHODS: Between March 2010 and March 2013, 3,689 consecutive ischemic stroke patients who were hospitalized within 4.5 h of onset were identified using a prospective stroke registry at 11 centers in Korea. Among them, patients with persistent ICAO after receiving IV tPA and whose 3-month modified Rankin Scale (mRS) was available were finally enrolled. A propensity score analysis with inverse-probability of treatment weighting was used to eliminate baseline imbalances between those receiving add-on EVT and IV tPA alone. RESULTS: Among 264 patients enrolled in this study (mean age 71.4; male 56.4%; median National Institute of Health Stroke Scale score 15), 117 (44.3%) received add-on EVT. The add-on EVT group had a higher frequency of favorable outcome on the mRS <=2 (35.0 vs. 18.4%; adjusted OR (aOR) 2.79; 95% CI 1.66-4.67) and lower mortality (17.9 vs. 35.4%; aOR 0.24; 95% CI 0.13-0.42) at 3 months, when compared to the IV tPA-alone group. Add-on EVT did not significantly increase the risk of symptomatic hemorrhage (5.1 vs. 4.1%; aOR 1.01; 95% CI 0.37 2.70). The rate of successful recanalization (thrombolysis in cerebral infarction grade >=2b) in the add-on EVT group was 69.2%. CONCLUSIONS: Compared to an IV tPA alone, add-on EVT can improve clinical outcomes in patients with symptomatic ICAO within 4.5 h of onset without a significant increase of symptomatic hemorrhage. PMID- 27359225 TI - Joint attention enhances visual working memory. AB - Joint attention-the mutual focus of 2 individuals on an item-speeds detection and discrimination of target information. However, what happens to that information beyond the initial perceptual episode? To fully comprehend and engage with our immediate environment also requires working memory (WM), which integrates information from second to second to create a coherent and fluid picture of our world. Yet, no research exists at present that examines how joint attention directly impacts WM. To investigate this, we created a unique paradigm that combines gaze cues with a traditional visual WM task. A central, direct gaze 'cue' face looked left or right, followed 500 ms later by 4, 6, or 8 colored squares presented on one side of the face for encoding. Crucially, the cue face either looked at the squares (valid cue) or looked away from them (invalid cue). A no shift (direct gaze) condition served as a baseline. After a blank 1,000 ms maintenance interval, participants stated whether a single test square color was present or not in the preceding display. WM accuracy was significantly greater for colors encoded in the valid versus invalid and direct conditions. Further experiments showed that an arrow cue and a low-level motion cue-both shown to reliably orient attention-did not reliably modulate WM, indicating that social cues are more powerful. This study provides the first direct evidence that sharing the focus of another individual establishes a point of reference from which information is advantageously encoded into WM. (PsycINFO Database Record PMID- 27359226 TI - The development of scope insensitivity in sharing behavior. AB - The singularity effect of identifiable victims is described as the greater willingness to help a single, identified victim than to help a group of victims with the same need (whether victims are identified or not), which occurs even when the single victim is 1 of the group's members. The current research examines the development of this phenomenon in early childhood examining children's actual sharing behavior from the ages of 3.8 to 8.2. Our results show that although younger children are overall less willing to share with others, they give more of their endowment to a group of recipients than to a single recipient. However, this tendency reverses for older children and children with higher level of Theory of Mind, who exhibit the singularity effect by giving more of their endowment to a single, identified target. We discuss possible mechanisms behind this developmental pattern. (PsycINFO Database Record PMID- 27359227 TI - "Choosing the larger versus choosing the smaller: Asymmetries in the size congruity effect": Correction to Arend and Henik (2015). AB - Reports an error in "Choosing the larger versus choosing the smaller: Asymmetries in the size congruity effect" by Isabel Arend and Avishai Henik (Journal of Experimental Psychology: Learning, Memory, and Cognition, 2015[Nov], Vol 41[6], 1821-1830). In the article the wrong version of Figure 1 was published. The correct version is provided. (The following abstract of the original article appeared in record 2015-23893-001.) The size congruity effect (SiCE) shows that number and physical size interact as magnitudes. That is, response times are faster when number and size are congruent (e.g., 2 4) than when they are incongruent (e.g., 2 4). A shared representational system has been the most influential account for the SiCE. Recently, this account has been challenged by findings showing that the SiCE may be influenced by attention. The attentional contribution to the SiCE suggests that the effect is produced by an attention capture effect to the larger stimulus. Even though plausible, the attentional account overlooks 2 important factors in the study of magnitudes, namely, task (numerical vs. physical) and polarity of instructions (choose the larger vs. the smaller). We studied the influence of these factors using a size congruity task. Experiment 1 showed that the SiCE was modulated by task and instructions. In Experiment 2, we used a new set of numbers to examine a possible influence of the so-called end effect (i.e., responses to the smallest and to the largest numbers may not require number comparison). Experiment 2 successfully replicated the pattern of Experiment 1. We suggest that both feature saliency and long-term semantic processes modulate the SiCE. (PsycINFO Database Record PMID- 27359228 TI - [Not Available]. PMID- 27359229 TI - [Not Available]. PMID- 27359230 TI - [Not Available]. PMID- 27359231 TI - [Not Available]. PMID- 27359232 TI - [Not Available]. PMID- 27359233 TI - [Sufficient high frequency jet ventilation during a period of 2.5 h - Airway management during resection of a tracheaesophageal fistula and tracheal resection]. AB - We present a 54 year old female patient who had undergone a Ross procedure in 2009, and in 2013 again a replacement of the aortic root and arch with bioprothetic material and homograft replacement of the pulmonalis walve. Postoperatively the patient had experienced a functional compromising tracheal stenosis and a persistent esophago-tracheal fistula. Endoscopic attempts to close the fistula were not successful, and the fistula was "bridged" with an endoscopically positioned tracheal stent.We report the anaesthesiological management during the open surgical repair of the esophago-tracheal fistula and resection of 2 tracheal rings with high frequency jet ventilation over a period of 2.5 h. The Patient was discharged from hospital on the 17. postoperative day. PMID- 27359234 TI - [Hyperoxia in Anesthesia and Intensive Care Medicine - too much of a good thing?]. AB - For decades the administration of oxygen has been a corner stone in the treatment of various medical emergencies, e.g. acute myocardial infarction. Several arguments support the perioperative use of high oxygen concentrations (>80%) for the prevention of surgical site infections. However, effects of oxygen include an increase in systemic vascular resistance, a reduction in heart rate and stroke volume and thus an impairment of the microcirculation, e.g. in the coronary and cerebral vasculature. Adequately powered, prospective, randomized, blinded outcome studies on the effects of hyperoxia in anesthesia and intensive care medicine are scarce. Recent data suggest that hyperoxia may be more harmful than beneficial and may increase morbidity and mortality in surgical and intensive care patients. Also, the current guidelines from the European Resuscitation Council from 2015 address the potentially harmful effects of high oxygen concentrations in various emergency settings. The aim of this article is to give an overview about the physiological and clinical effects of hyperoxia with a focus on its use in perioperative and intensive care medicine. PMID- 27359235 TI - [Weaning: more than terminating mechanical ventilation]. AB - Mechanical ventilation is an essential part of modern intensive care. It is used in patients with acute respiratory failure and, depending on the type of respiratory failure, different modes of application. In particular, invasive mechanical ventilation should be terminated as raidly as possible to avoid the associated risks.The major proportion of ventilated patients can be weaned from mechanical ventilation without problems after a short treatment period. In about 20% of ventilated patients, however, an extremely protracted and complex weaning process can be observed, even though the cause necessitating ventilation has long since been eliminated. In addition to the stages in the process of weaning from the ventilator, in particular the pathophysiological processes that lead to prolonged weaning are addressed in this article. PMID- 27359236 TI - [Not Available]. PMID- 27359237 TI - [Not Available]. PMID- 27359238 TI - [Pathophysiology, diagnosis and treatment of asthma: focusing on a chronic disease]. AB - Bronchial asthma is one of the most common chronic diseases. Its pathogenesis is still not fully understood and its progression is still not predictable. There are individual differences in frequency, severity and duration of symptoms and progression as well as in the response to therapy. The diagnosis is based on a detailed medical history and physical examination, on lung function tests and allergy tests. In recent years great improvements in medical treatment and patient care have been achieved. This article summarizes the pathogenesis, clinical picture, diagnosis and treatment of bronchial asthma. PMID- 27359239 TI - [Anesthetic management in bronchial asthma]. AB - In daily practice, acute and chronic pulmonary diseases are common issues presenting to the anesthetist. Respiratory physiology in general is affected by both general and regional anesthesia, which results in an increased number of perioperative complications in pulmonary risk patients. Therefore, anesthetic management of patients with bronchial asthma needs to address different clinical topics: the physical appearance of pulmonary disease, type and extent of surgical intervention as well as effects of therapeutic drugs, anesthetics and mechanical ventilation on respiratory function. The present work describes important precautions in preoperative scheduling of the asthmatic patient. In the operative course, airway manipulation and a number of anesthetics are able to trigger intraoperative bronchial spasm with possibly fatal outcome. It is essential to avoid these substances to prevent asthma attack. If asthmatic status occurs, appropriate procedures according to therapeutic standards have to be applied to the patient. Postoperatively, sufficient pain therapy avoids pulmonary complications and improves outcome. PMID- 27359240 TI - [Asthma bronchiale - Emergency medical treatment]. AB - Treatment of patients with acute severe or life-threatening asthma in the emergency department or in rescue services is a challenge for the physician. The decision on which therapy is needed depends on the clinical assessment of severity. Early administration of bronchodilators, ipratropium bromide and oral or intravenous corticosteroids is the cornerstone of treatment. If these treatments fail, systemic administration of bronchodilators, MgSO4 and theophylline should be carried in order to avoid intubation. Patients with incomplete or poor response should stay in hospital. PMID- 27359241 TI - [Not Available]. PMID- 27359242 TI - [Not Available]. PMID- 27359243 TI - Fundamental High-Speed Limits in Single-Molecule, Single-Cell, and Nanoscale Force Spectroscopies. AB - Force spectroscopy is enhancing our understanding of single-biomolecule, single cell, and nanoscale mechanics. Force spectroscopy postulates the proportionality between the interaction force and the instantaneous probe deflection. By studying the probe dynamics, we demonstrate that the total force acting on the probe has three different components: the interaction, the hydrodynamic, and the inertial. The amplitudes of those components depend on the ratio between the resonant frequency and the frequency at which the data are measured. A force-distance curve provides a faithful measurement of the interaction force between two molecules when the inertial and hydrodynamic components are negligible. Otherwise, force spectroscopy measurements will underestimate the value of unbinding forces. Neglecting the above force components requires the use of frequency ratios in the 50-500 range. These ratios will limit the use of high speed methods in force spectroscopy. The theory is supported by numerical simulations. PMID- 27359244 TI - TiO2 Nanoparticle Uptake by the Water Flea Daphnia magna via Different Routes is Calcium-Dependent. AB - Calcium plays versatile roles in aquatic ecosystems. In this study, we investigated its effects on the uptake of polyacrylate-coated TiO2 nanoparticles (PAA-TiO2-NPs) by the water flea (cladoceran) Daphnia magna. Particle distribution in these daphnids was also visualized using synchrotron radiation based micro X-ray fluorescence spectroscopy, transmission electron microscopy, and scanning electron microscopy. At low ambient Ca concentrations in the experimental medium ([Ca]dis), PAA-TiO2-NPs were well dispersed and distributed throughout the daphnid; the particle concentration was highest in the abdominal zone and the gut, as a result of endocytosis and passive drinking of the nanoparticles, respectively. Further, Ca induced PAA-TiO2-NP uptake as a result of the increased Ca influx. At a high [Ca]dis, the PAA-TiO2-NPs formed micrometer sized aggregates that were ingested by D. magna and concentrated only in its gut, independent of the Ca influx. Our results demonstrated the multiple effects of Ca on nanoparticle bioaccumulation. Specifically, well-dispersed nanoparticles were taken up by D. magna through endocytosis and passive drinking whereas the uptake of micrometer-sized aggregates relied on active ingestion. PMID- 27359245 TI - Gel Point Suppression in RAFT Polymerization of Pure Acrylic Cross-Linker Derived from Soybean Oil. AB - Here we report the reversible addition-fragmentation chain transfer (RAFT) polymerization of acrylated epoxidized soybean oil (AESO), a cross-linker molecule, to high conversion (>50%) and molecular weight (>100 kDa) without macrogelation. Surprisingly, gelation is suppressed in this system far beyond the expectations predicated both on Flory-Stockmeyer theory and multiple other studies of RAFT polymerization featuring cross-linking moieties. By varying AESO and initiator concentrations, we show how intra- versus intermolecular cross linking compete, yielding a trade-off between the degree of intramolecular linkages and conversion at gel point. We measured polymer chain characteristics, including molecular weight, chain dimensions, polydispersity, and intrinsic viscosity, using multidetector gel permeation chromatography and NMR to track polymerization kinetics. We show that not only the time and conversion at macrogelation, but also the chain architecture, is largely affected by these reaction conditions. At maximal AESO concentration, the gel point approaches that predicted by the Flory-Stockmeyer theory, and increases in an exponential fashion as the AESO concentration decreases. In the most dilute solutions, macrogelation cannot be detected throughout the entire reaction. Instead, cyclization/intramolecular cross-linking reactions dominate, leading to microgelation. This work is important, especially in that it demonstrates that thermoplastic rubbers could be produced based on multifunctional renewable feedstocks. PMID- 27359246 TI - Does the whistling thorn acacia (Acacia drepanolobium) use auditory aposematism to deter mammalian herbivores? AB - Auditory signaling including aposematism characterizes many terrestrial animals. Auditory aposematism by which certain animals use auditory aposematic signals to fend off enemies is well known for instance in rattlesnakes. Auditory signaling by plants toward animals and other plants is an emerging area of plant biology that still suffers from limited amount of solid data. Here I propose that auditory aposematism operates in the African whistling thorn acacia (Acacia drepanolobium = Vachellia drepanolobium). In this tree, the large and hollow thorn bases whistle when wind blows. This type of aposematism compliments the well-known conspicuous thorn and mutualistic ant based aposematism during day and may operate during night when the conspicuous thorns are invisible. PMID- 27359247 TI - Fused Perovskite Tunnel Structures in Ba5 Fe6+x S4+x O8 (0.44<=x<=0.55) with x Dependent Two-Stage Magnetizations. AB - Ba5 Fe6+x S4+x O8 was synthesized through a solid-state reaction, and pure powders of nominal compositions x=0.44-0.55 were obtained after being rinsed with water. The crystal structures (P4/mmm, a=10.13, c=4.03 A) and sample purities were investigated by powder synchrotron X-ray diffraction and were found to be composed of a tunnel lattice (Ba5 Fe6 S4 O8 ), built from fused perovskite units and the tunnel filling (Fex Sx ). The variable composition, that is, the tunnel filling (x), causes partially occupied sites as well as crystallographic split positions. Ba5 Fe6+x S4+x O8 (x=0.525) is semiconducting and all investigated compositions exhibit magnetic ground states that could be described as either semi-spin-glass-like (x>0.5) or canted antiferromagnetic (x<0.5). The spin-glass in x=0.525 exhibits magnetic relaxations that are affected by ageing. PMID- 27359248 TI - Potential Pathogens Reported in Species of the Family Viverridae and Their Implications for Human and Animal Health. AB - The Viverridae is a family of nocturnal carnivores including civets, genets and African linsangs. While a list of known organisms isolated from a species is an essential tool for population management, this review represents the first attempt to collate published reports of organisms isolated from viverrids. A wide range of organisms, including 11 viruses, eight bacterial species, one internal arthropod species, representatives from eight genera of protozoan, 21 genera of nematode, seven genera of cestode, eight genera of trematode and six genera of external arthropod (mites, ticks and louse), have been reported in literature spanning over a century of research. Many of these are capable of infecting multiple hosts, including humans. This is of concern given the anthropogenic factors that bring humans and domestic species into close contact with viverrids, facilitating transmission and spillover of organisms between groups. These factors include trade in viverrids for human consumption, captive management in zoos, rescue centres or on commercial breeding farms, and the increasing overlap of free-ranging viverrid distribution and human settlement. PMID- 27359249 TI - Identification of a novel endophytic Bacillus sp. from Capsicum annuum with highly efficient and broad spectrum plant probiotic effect. AB - AIM: The study mainly aimed the isolation and characterization of plant probiotic endophytic bacteria from Capsicum annuum to explore its multipotent agricultural applications. MATERIALS AND METHODS: Endophytic bacteria were isolated from the surface sterilized fruit tissue. The isolates were then subjected to PCR-based screening for the presence of potential biosynthetic gene clusters. The PCR positive isolate was then analysed for its inhibitory effect towards fungal and bacterial pathogens. The compounds responsible for the antimicrobial activity was purified from large scale culture and subjected to identification by LC-MS/MS. The ability of the selected isolate in plant growth enhancement was also done using Vigna radiata seedlings. CONCLUSION: In this study, an endophytic bacterium isolated from C. annuum was found to have the phenotypic and genetic basis for broad antimicrobial property. PCR-based sequence analysis has resulted in the identification of nonribosomal peptide synthases, PKS Type I, Iturin, surfactin, DAPG and gacA genes in the selected isolate CaB 5. The bioactivity-guided fractionation using column and HPLC purification of active fraction followed by LC-MS/MS analysis has proved the presence of surfactin derivatives (M+H(+) - 1008 & 1036) and iturin (M+H(+) - 1058) as the basis of antimicrobial activity of CaB 5. The isolate was identified as a novel Bacillus sp. because of its low (76%) identity to the reported sequences. SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytes are considered to have the genetic basis for a diverse array of bioactive metabolites which can have significant applications in both pharmaceutical industry and agriculture. The identification of CaB 5 with broad bioactivity and excellent plant growth enhancement on taxonomically distinct plant species as explained in current study and our previous reports highlights its plant probiotic applicability. This proves the potential of the isolate obtained in the study to be an excellent plant probiotic. PMID- 27359250 TI - Parent and Child ADHD Symptoms in Relation to Parental Attitudes and Parenting: Testing the Similarity-Fit Hypothesis. AB - OBJECTIVE: We tested the similarity-fit hypothesis that predicts more positive parenting when both parent and child have high levels of ADHD symptoms compared to when only one does. METHOD: Mothers and fathers of 156, 5 to 13 year old sons participated (110 boys with ADHD, 46 without). Parent inattentive and hyperactive impulsive symptoms were examined, in interaction with child ADHD, as predictors of parental tolerance, empathy, encouragement of child autonomy, and positive parenting. RESULTS: Several interactions of parent ADHD symptoms and child ADHD were detected which suggested that for parents with low levels of symptoms, the presence of child ADHD was associated with less positive parenting attitudes and behavior, but this negative relation between positive parenting and child ADHD was dampened among parents with more ADHD symptoms. CONCLUSIONS: Considered alongside the well documented parenting difficulties associated with parental ADHD, our findings suggest that parental ADHD symptoms also may help to mitigate some of the challenges facing families of children with ADHD. PMID- 27359251 TI - Focal intestinal lipogranulomatous lymphangitis in 10 dogs. AB - OBJECTIVES: To describe the clinical and pathological features of canine focal lipogranulomatous lymphangitis, to evaluate its underlying infectious cause and to compare it with human Crohn's disease. METHODS: Retrospective review of case records with a histopathological diagnosis of focal lipogranulomatous lymphangitis. Bacterial and fungal colonisation was evaluated using fluorescence in situ hybridisation and histochemical staining, respectively. A comparison with Crohn's disease was performed by a human pathologist. RESULTS: Ten dogs were evaluated. The historical complaints were predominantly chronic diarrhoea (10/10) and vomiting (5/10). The biochemical abnormalities included hypoalbuminaemia (6/10) and hypocobalaminaemia (4/6). Abdominal sonography revealed a thickened distal ileum+/-ileocolic junction. Colonoscopy showed a swollen caecal ostium and oedematous caecum in 7/10 dogs. A stenotic ileo-colic opening prevented endoscopic intubation in all dogs. Histology from the resected lesions revealed granulomatous inflammation involving the muscularis and serosa. Fluorescence in situ hybridization demonstrated invasive bacteria in 2/10 dogs. Post-resection, all dogs received metronidazole and tapering immunosuppressive doses of prednisolone. Remission (median 17 months) was achieved in 8/10 dogs. CLINICAL SIGNIFICANCE: Focal lipogranulomatous lymphangitis is a rare and severe form of canine inflammatory bowel disease with preferential localisation to the ileum and the ileocolic junction. An underlying infectious aetiology was not identified. PMID- 27359252 TI - Modulating Electron Sharing in Ion-pi-Receptors via Substitution and External Electric Field: A Route toward Bond Strengthening. AB - Substituted coronenes, a family of ion-pi receptors whose ion-affinities can be explained exclusively neither via ion-quadrupole nor induction/polarization mechanisms, are studied. The best descriptors of ion-affinity among these species are those characterizing charge-transfer between ions and the pi-systems, e.g. vertical ionization potential, electron affinity, and the relative energies of charge-transfer excited-states (CTESs). The variation of the electric multipole moments, polarizability, binding energy, and relative energy of CTESs in the presence of an external electric field (EEF) is evaluated. The results indicate that the EEF has a negligible effect on the polarizability and quadrupole moment of the systems. However, it significantly affects the binding energies, CTES energies, and the dipole moments of the receptors. Contrary to the changes in the dipole moment, the variation pattern of the binding energy is more consistent with the pattern observed for the CTES energy changes. Finally, by analyzing the exchange-correlation component of the binding energy we demonstrate that the increased binding energy, i.e. bond strengthening, originates from enhanced electron sharing and multicenter covalency between the ions and the pi-systems as a result of the state-mixing between the ground-state and the CTESs. According to our findings, we hypothesize that the electron sharing and in extreme cases the multicenter covalency are the main driving forces for complexation of ions with extended pi-receptors such as carbon nanostructures. PMID- 27359254 TI - An Ultrahydrophobic Fluorous Metal-Organic Framework Derived Recyclable Composite as a Promising Platform to Tackle Marine Oil Spills. AB - Derived from a strategically chosen hexafluorinated dicarboxylate linker aimed at the designed synthesis of a superhydrophobic metal-organic framework (MOF), the fluorine-rich nanospace of a water-stable MOF (UHMOF-100) exhibits excellent water-repellent features. It registered the highest water contact angle (~176 degrees ) in the MOF domain, marking the first example of an ultrahydrophobic MOF. Various experimental and theoretical studies reinforce its distinctive water repellent characteristics, and the conjugation of superoleophilicity and unparalleled hydrophobicity of a MOF material has been coherently exploited to achieve real-time oil/water separation in recyclable membrane form, with significant absorption capacity performance. This is also the first report of an oil/water separating fluorinated ultrahydrophobic MOF-based membrane material, with potential promise for tackling marine oil spillages. PMID- 27359255 TI - Enantioselective sulfoxidation reaction catalyzed by a G-quadruplex DNA metalloenzyme. AB - Enantioselective sulfoxidation reaction is achieved for the first time by a DNA metalloenzyme assembled with the human telomeric G-quadruplex DNA and Cu(ii)-4,4' bimethyl-2,2'-bipyridine complex, and the mixed G-quadruplex architectures are responsible for the catalytic enantioselectivity and activity. PMID- 27359253 TI - Genome-wide studies of von Willebrand factor propeptide identify loci contributing to variation in propeptide levels and von Willebrand factor clearance. AB - Essentials Variants at ABO, von Willebrand Factor (VWF) and 2q12 contribute to the variation in plasma in VWF. We performed a genome-wide association study of plasma VWF propeptide in 3,238 individuals. ABO, VWF and 2q12 loci had weak or no association or linkage with plasma VWFpp levels. VWF associated variants at ABO, VWF and 2q12 loci primarily affect VWF clearance rates. SUMMARY: Background Previous studies identified common variants at the ABO and VWF loci and unknown variants in a chromosome 2q12 linkage interval that contributed to the variation in plasma von Willebrand factor (VWF) levels. Whereas the association with ABO haplotypes can be explained by differential VWF clearance, little is known about the mechanisms underlying the association with VWF single-nucleotide polymorphisms (SNPs) or with variants in the chromosome 2 linkage interval. VWF propeptide (VWFpp) and mature VWF are encoded by the VWF gene and secreted at the same rate, but have different plasma half-lives. Therefore, comparison of VWFpp and VWF association signals can be used to assess whether the variants are primarily affecting synthesis/secretion or clearance. Methods We measured plasma VWFpp levels and performed genome-wide linkage and association studies in 3238 young and healthy individuals for whom VWF levels had been analyzed previously. Results and conclusions Common variants in an intergenic region on chromosome 7q11 were associated with VWFpp levels. We found that ABO serotype-specific SNPs were associated with VWFpp levels in the same direction as for VWF, but with a much lower effect size. Neither the association at VWF nor the linkage on chromosome 2 previously reported for VWF was observed for VWFpp. Taken together, these results suggest that the major genetic factors affecting plasma VWF levels, i.e. variants at ABO, VWF and a locus on chromosome 2, operate primarily through their effects on VWF clearance. PMID- 27359256 TI - Assessment of Staffing, Services, and Partnerships of Local Health Departments - United States, 2015. AB - Beginning in 2008, the National Association of County and City Health Officials (NACCHO) periodically surveyed local health departments (LHDs) to assess the impact of the economic recession on jobs and budgets (1). In 2014, the survey was expanded to assess a wider range of factors affecting programs, services, and infrastructure in LHDs and renamed the Forces of Change survey (2). The survey was administered in to January-February 2015 to 948 LHDs across the United States to assess budget changes, job losses, changes in services, and collaboration with health care partners; 690 (73%) LHDs responded. Findings indicated a change in LHD infrastructure: compared with the previous fiscal year.* Overall, LHDs reported 3,400 jobs lost; 25% of LHDs reported budget decreases; 36% reported a reduction in at least one service area; and 35% reported serving fewer patients in clinics. In addition, up to 24% of LHDs reported expanding population-based prevention services, and LHDs reported exploring new collaborations with nonprofit hospitals and primary care providers (PCPs). PMID- 27359257 TI - Laboratory-Scale Membrane Reactor for the Generation of Anhydrous Diazomethane. AB - A configurationally simple and robust semibatch apparatus for the in situ on demand generation of anhydrous solutions of diazomethane (CH2N2) avoiding distillation methods is presented. Diazomethane is produced by base-mediated decomposition of commercially available Diazald within a semipermeable Teflon AF 2400 tubing and subsequently selectively separated from the tubing into a solvent and substrate-filled flask (tube-in-flask reactor). Reactions with CH2N2 can therefore be performed directly in the flask without dangerous and labor intensive purification operations or exposure of the operator to CH2N2. The reactor has been employed for the methylation of carboxylic acids, the synthesis of alpha-chloro ketones and pyrazoles, and palladium-catalyzed cyclopropanation reactions on laboratory scale. The implementation of in-line FTIR technology allowed monitoring of the CH2N2 generation and its consumption. In addition, larger scales (1.8 g diazomethane per hour) could be obtained via parallelization (numbering up) by simply wrapping several membrane tubings into the flask. PMID- 27359258 TI - Generation of pediatric liver cancer patient-derived xenograft platforms for pediatric liver cancer: A critical stage in the development of anticancer treatments. PMID- 27359259 TI - DIAGNOSIS OF TYPE 3 NEOVASCULARIZATION BASED ON OPTICAL COHERENCE TOMOGRAPHY IMAGES. AB - PURPOSE: To evaluate the concordance of an optical coherence tomography (OCT) based diagnosis of Type 3 neovascularization and an indocyanine green angiography (ICGA)-based diagnosis in neovascular age-related macular degeneration (AMD). METHODS: This observational case series includes 263 eyes from 263 patients who were diagnosed with treatment-naive neovascular AMD. Patients exhibiting at least three of the following OCT features were diagnosed with Type 3 neovascularization: subfoveal choroidal thickness <200 MUm, presence of intraretinal fluid accumulation, absence of subretinal fluid, gently-sloping dome shaped retinal pigment epithelial detachment or trapezoid-shaped retinal pigment epithelial detachment without an obvious peak, and intraretinal mass lesion. The incidence of cases exhibiting three or more OCT features was compared among different subtypes of neovascular AMD. Additionally, the concordance of OCT-based diagnosis and ICGA-based diagnosis was evaluated. RESULTS: Three or more OCT features were noted in 8 of 82 (9.8%) eyes with typical neovascular AMD, 4 of 147 (2.7%) eyes with polypoidal choroidal vasculopathy, and 30 of 34 (88.2%) eyes with Type 3 neovascularization, respectively. The incidence was significantly greater in Type 3 neovascularization than in the other subtypes of neovascular AMD (P < 0.001). Of patients diagnosed with Type 3 neovascularization using ICGA based methods, 88.2% were also diagnosed with Type 3 neovascularization using OCT based methods. Only 5.2% of patients diagnosed with other subtypes of neovascular AMD using ICGA-based methods were diagnosed with Type 3 neovascularization using OCT-based methods. CONCLUSION: Optical coherence tomography-based diagnosis of Type 3 neovascularization showed relatively high concordance compared with ICGA based diagnosis. This method may be useful in clinical practice. PMID- 27359260 TI - One-Pot Synthesis of Substituted Trifluoromethylated 2,3-Dihydro-1H-imidazoles. AB - An operationally simple one-pot reaction for the preparation of a novel class of racemic trifluoromethylated 2,3-dihydro-1H-imidazoles derived from electron-poor N,O-acetals and aryl Grignard reagents is described. In addition, access to highly functionalized 2-trifluoromethyl-2,3-dihydro-1H-imidazoles was accomplished by reaction of N-aryl hemiaminal ethers and N-aryl trifluoroethylamines in the presence of an excess of n-butyllithium. PMID- 27359261 TI - No-Loss Transportation of Water Droplets by Patterning a Desired Hydrophobic Path on a Superhydrophobic Surface. AB - The directional transportation of droplets on solid surfaces is essential in a wide range of engineering applications. It is convenient to guide liquid droplets in a given direction by utilizing the gradient of wettability, by which the binding forces can be produced. In contrast to the mass-loss transportation of a droplet moving along hydrophilic paths on a horizontal superhydrophobic surface, we present no-loss transportation by fabricating a hydrophobic path on the same surface under tangential wind. In experimental exploration and theoretical analysis, the conditions of no-loss transportation of a droplet are mainly considered. We demonstrate that the lower (or upper) critical wind velocity, under which the droplet starts on the path (or is derailed from the path), is determined by the width of the path, the length of the contact area in the direction parallel to the path, the drift angle between the path and the wind direction, and the surface wettability of the pattern. Meanwhile, the no-loss transportation of water droplets along the desired path zigzagging on a superhydrophobic surface can be achieved steadily under appropriate conditions. We anticipate that such robust no-loss transportation will find an extensive range of applications. PMID- 27359262 TI - Price analysis of multiple sclerosis disease-modifying therapies marketed in the United States. AB - OBJECTIVES: This study assessed trends in the average wholesale price (AWP) at the market entry of disease-modifying therapies (DMTs) approved by Food and Drug Administration (FDA) in the period 1987-2014. METHODS: DMT regulatory information was derived from the FDA website. The AWPs per unit at market entry data were derived from the Red Book (Truven Health Analytics Inc.). The AWP history for each DMT was collected from its date of approval to 31 December 2014. The FDA approved label defined daily dose (DDD) for adult patients was obtained from FDA approved labels. The AWP per DDD and the AWP/DDD per year of therapy were computed. Descriptive statistics, Wilcoxon tests, t-test, and multiple linear regression were performed. The statistical significance level was set at 0.05. RESULTS: The FDA approved 12 multiple sclerosis (MS) DMTs, including five new drug applications (NDAs) and seven biologic license applications (BLAs) as of 31 December 2014. The FDA granted orphan designation to five DMTs. There was one DMT approved by the FDA in the 1980s, three in the 1990s, three in 2000s, and five in the period 2010-2014. The market entry inflation-adjusted AWP per DDD was $10.23 for the first DMT (mitoxantrone hydrochloride) that was approved in the 1980s. The median market entry inflation-adjusted AWP per DDD was $12.41 (interquartile range [IQR] = 4.51) for DMTs approved in the 1990s, $71.26 (IQR = 58.35) in the 2000s, and $172.56 (IQR = 84.97) in the period 2010-2014. The median AWP per DDD was statistically significantly different (p = 0.011) for orphan (median = $41.82, IQR = 56.077) compared to non-orphan drugs (median = $171.32, IQR = 199.29). Year of market entry was positively associated with DMT prices at US market entry (p = 0.01). CONCLUSIONS: The AWP per DDD for DMTs at market entry increased substantially over time. The increase in DMTs prices exceeded the general consumer price index. PMID- 27359263 TI - H-type hypertension is an important risk factor of carotid atherosclerotic plaques. AB - AIM: To investigate the association of H-type hypertension with carotid atherosclerotic plaques in Chinese. METHODS: This hospital-based large population study included 13192 patients and all the patients were sequentially recruited between May 2010 and May 2013 at the Health Medical Center of the Chinese PLA General Hospital. The subjects were divided into four groups: the H-type of hypertension group, isolated systolic hypertension, simple homocysteine (Hcy) group, and the control group without hypertension and Hcy. Univariate logistic regression analysis was performed to investigate the association of H-type hypertension with the odds of carotid atherosclerotic plaques. RESULTS: Among the 13192 subjects, there were 9007 (68.28% of all subjects) patients with hyperhomocysteinemia and 3543 patients with H-type hypertension, which was 26.86% of all subjects and 74.45% of hypertension patients. 34.55% of all subjects (4558) had carotid atherosclerotic plaques. The carotid atherosclerotic plaques positive rate among four groups was significantly different (chi(2) = 647.8988, P = 0.000). The carotid atherosclerotic plaques' positive rate of patients with H type hypertension was 49.31%, which was significantly higher than the other three groups. Univariate logistic regression analysis results indicated that significant correlations exist between high-Hcy hypertension and carotid atherosclerotic plaques. Incidence of carotid atherosclerotic plaques in H-type hypertension patients was 1.63 times that in patients with isolated systolic hypertension. CONCLUSION: H-type hypertension is independently associated with higher risk of carotid atherosclerotic plaques. H-type hypertension and Hcy should be the major intervention measures to decrease the incidence of carotid atherosclerotic plaques as well as the stroke in Health Practice Management. PMID- 27359264 TI - Multilocus Sequence Typing of Strains of Bacterial Spot of Lettuce Collected in the United States. AB - Studies on genetic diversity and recombination in bacterial pathogens are providing a better understanding of the mechanisms shaping bacterial diversity, which can affect disease control. Xanthomonas campestris pv. vitians, causal agent of bacterial leaf spot of lettuce, is a threat to the worldwide lettuce industry. We examined the genetic variation within a sample of 83 strains from California, Florida, and Ohio using multilocus sequence typing of six housekeeping genes, totaling 2.7 kb. Additionally, polymorphism in two virulence related genes, hrpB2 and a putative glycosyl hydrolase, were examined. Based on housekeeping genes, we found three genetic groups of strains that were all able to induce the disease. These included strains collected from weeds and irrigation water that had haplotypes identical to strains from diseased lettuce. High linkage disequilibrium across the sequenced loci indicates that the pathogen is predominantly clonal but recombination has contributed to the observed sequence variation. Although there was significant genetic variation in X. campestris pv. vitians within and among sampled states, identical haplotypes were observed across all three states. This finding suggests that seedborne inoculum may contribute to the diversity of X. campestris pv. vitians in the United States. Knowledge of the genetic structure of the pathogen may be used for developing resistant lettuce varieties. PMID- 27359265 TI - Competitive Fitness of Phakopsora pachyrhizi Isolates with Mutations in the CYP51 and CYTB Genes. AB - Soybean rust (Phakopsora pachyrhizi) in Brazil is mainly controlled with applications of fungicides, including demethylation inhibitors (DMI) and quinone outside inhibitors (QoI). Isolates with less sensitivity to DMI and QoI have been reported, and these have been found to have mutations in the CYP51 and CYTB genes, respectively. There have been no reports of fitness costs in isolates with mutations in CYP51 and CYTB, and the aim of this work was to compare the competitive ability of isolates with lower DMI or QoI sensitivities with that of sensitive (wild-type) isolates. Urediniospores of sensitive wild-type isolates and isolates with different CYP51 or CYTB alleles were mixed and inoculated on detached soybean leaves. After 3 weeks, urediniospores were harvested and used as inoculum for the next disease cycle. Frequencies of relevant target site mutations were monitored using the pyrosequencing method over four disease cycles. Isolates with lower DMI sensitivity and different CYP51 alleles had competitive disadvantages compared with a DMI-sensitive, wild-type CYP51 isolate. In contrast, the isolate with the F129L mutation in the CYTB gene competed equally well with a QoI-sensitive, wild-type CYTB isolate under the conditions of this experiment. The CYP51 and CYTB alleles were stable in all isolates over four disease cycles when cultivated alone. PMID- 27359267 TI - Editorial. PMID- 27359266 TI - Markers Linked to Wheat Stem Rust Resistance Gene Sr11 Effective to Puccinia graminis f. sp. tritici Race TKTTF. AB - Wheat stem rust, caused by Puccinia graminis f. sp. tritici, can cause severe yield losses on susceptible wheat varieties and cultivars. Although stem rust can be controlled by the use of genetic resistance, population dynamics of P. graminis f. sp. tritici can frequently lead to defeat of wheat stem rust resistance genes. P. graminis f. sp. tritici race TKTTF caused a severe epidemic in Ethiopia on Ug99-resistant 'Digalu' in 2013 and 2014. The gene Sr11 confers resistance to race TKTTF and is present in 'Gabo 56'. We identified seven single nucleotide polymorphism (SNP) markers linked to Sr11 from a cross between Gabo 56 and 'Chinese Spring' exploiting a 90K Infinium iSelect Custom beadchip. Five SNP markers were validated on a 'Berkut'/'Scalavatis' population that segregated for Sr11, using KBioscience competitive allele-specific polymerase chain reaction (KASP) assays. Two of the SNP markers, KASP_6BL_IWB10724 and KASP_6BL_IWB72471, were predictive of Sr11 among wheat genetic stocks, cultivars, and breeding lines from North America, Ethiopia, and Pakistan. These markers can be utilized to select for Sr11 in wheat breeding and to detect the presence of Sr11 in uncharacterized germplasm. PMID- 27359268 TI - Efficacy of crizotinib in first-line treatment of adults with ALK-positive advanced NSCLC. AB - INTRODUCTION: The treatment of advanced non-small cell lung cancer (NSCLC) has evolved from palliative cytotoxic chemotherapy to precise medicine based on genetic alternations over the last decade. Anaplastic lymphoma kinase (ALK) rearrangement characterizes a molecular subset of NSCLC with an impressive response to crizotinib. AREAS COVERED: To analyze the efficacy of crizotinib in first-line treatment of adults with advanced ALK-positive NSCLC, updated data on development and recent advances of first-line crizotinib in this subset population are reviewed. EXPERT OPINION: To date, crizotinib should be established as a standard of care in previously untreated advanced NSCLC with ALK rearrangement. However, the efficacy of first-line crizotinib is limited by acquired resistance. Second generation ALK inhibitors have demonstrated clinical activity in both crizotinib-refractory and crizotinib naive setting. How to maximize first-line benefit for advanced ALK-positive NSCLC remains challenging. Combinational strategy, advances in companion diagnostics and optimization of ALK inhibitors might contribute to improve outcome in this subset of patients in future. PMID- 27359272 TI - Sub-Nanosecond Resonance Energy Transfer in the Near-Infrared within Self Assembled Conjugates of PbS Quantum Dots and Cyanine Dye J-Aggregates. AB - Energy transfer (EnT) of near-infrared (NIR) excitons enables applications in harvesting of solar energy and biological imaging. Fast exciton extraction from NIR-absorbing Pb-chalcogenide quantum dots (QDs) may allow utilization of the photon downconversion (multiple exciton generation) process that occurs in those QDs to amplify signal in QD-based sensors or photocurrent in QD-based photovoltaics. This paper describes subnanosecond extraction of NIR excitons from PbS QDs by adsorbed J-aggregates of cyanine dye in aqueous dispersions. The QD/J aggregate complexes form through electrostatic self-assembly, and the rate and yield of EnT within the complexes can be optimized by adjusting spectral overlap between QD emission and the J-aggregate absorption, which are controlled by density of charged ligands on the QD surface and the pH. The primary EnT pathways have rate constants ranging from (800 ps)(-1) to (2.2 ns)(-1), which are 1-2 orders of magnitude faster than previously reported examples with PbS QDs as exciton donors. The fastest EnT process occurs in 90 ps and is potentially competitive with Auger recombination of biexcitonic states in PbS QDs. PMID- 27359273 TI - Transbronchial Saline Injection to Allow Visualization and Biopsy of Peripheral Lung Nodule on Linear Endobronchial Ultrasound. AB - Two peripheral lung nodules suspicious for lung cancer were noted in a patient. Surgical and CT-guided transthoracic needle biopsies were deemed to be high risk given advanced emphysema. The patient received nondiagnostic electromagnetic navigation bronchoscopy and endobronchial ultrasound (EBUS)-guided mediastinal needle biopsies. Repeat bronchoscopy was then performed. The lung nodules were difficult to visualize with both convex probe EBUS and electromagnetic navigation bronchoscopy guidance. Normal saline injection into vicinity of the peripheral lung nodule was then used in hopes of filling airspace with fluid and improving visualization of the lung nodule. After saline injection the nodule was visualized on convex probe EBUS, allowing for diagnostic needle aspirations. PMID- 27359274 TI - Pseudomembranous Tracheobronchitis: A Rare Presentation of Pseudomonas aeruginosa Infection. PMID- 27359275 TI - Embryonic Stage-Dependent Teratogenicity of Ketamine in Zebrafish (Danio rerio). AB - Ketamine, a widely used anesthetic, has been shown to have NMDA receptor dependent and independent actions during zebrafish (Danio rerio) embryogenesis. Notwithstanding, the effects of developmental toxicity and the mechanisms of ketamine action on fish embryos are still not well understood, and its implications for early vertebrate development remains to be clarified. In this work, zebrafish embryos were exposed to ketamine (0.2, 0.4, and 0.8 mg mL(-1)) in order to study the stage-developmental toxicity of this pharmaceutical. During 256-cell (2.5 h post-fertilization, hpf), 50% epiboly (5.5 hpf) and 1-4 somites (10.5 hpf), embryos were exposed to the referred ketamine concentrations for a period of 20 min and were allowed to grow until 144 hpf. Both lethal and nonlethal parameters were evaluated. Skeletal development was assessed by alcian blue and calcein staining. Additionally, the expression of the developmental genes sonic hedgehog a (shh a) and noggin 3 (nog3) was evaluated. Similar to our previous work, bone and cartilage malformations were observed after 256-cell exposure. During 50% epiboly, ketamine exposure induced concentration-dependent mortality and malformations, such as lordosis and/or kyphosis and microcephaly, namely, at higher concentrations. Conversely, exposure during 1-4 somites showed the induction of nonspecific effects with no rise in mortality. The quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed differences in shh a and nog3 expressions comparatively to the control group. Overall, this study shows that the ketamine toxic profile is developmental phase-dependent with 256 cell being the most susceptible phase. The effects observed may result from ketamine interaction with cellular signaling pathways that merits further investigation. PMID- 27359276 TI - Facile Fabrication of Ethoxy-Functional Polysiloxane Wrapped LiNi0.6Co0.2Mn0.2O2 Cathode with Improved Cycling Performance for Rechargeable Li-Ion Battery. AB - Dealing with the water molecule on the surface of LiNi0.6Co0.2Mn0.2O2 (NCM) cathode and hydrogen fluoride in the electrolyte is one of the most difficult challenges in Li-ion battery research. In this paper, the surface polymerization of tetraethyl orthosilicate (TEOS) on NCM to generate ethoxy-functional polysiloxane (EPS) wrapped NCM (E-NCM) cathode under mild conditions and without any additions is utilized to solve this intractable problem. The differential scanning calorimetry, transmission electron microscopy, and X-ray photoelectron spectroscopy results show that the formed amorphous coating can provide a protective shell to improve the NCM thermal stability, suppress the thickening of the solid electrolyte interphase (SEI) layer, and scavenge HF in the electrolyte. The E-NCM composite with 2 mol % EPS delivers a high discharge capacity retention of 84.9% after 100 cycles at a 1 C discharge rate in the 2.8-4.3 V potential range at 55 degrees C. Moreover, electrochemical impedance spectroscopy measurements reveal that the EPS coating could alleviate the impedance rise during cycling especially at an elevated temperature. Therefore, the fabricated E NCM cathode with long-term cycling and thermal stability is a promising candidate for use in a high-energy Li-ion battery. PMID- 27359277 TI - Arabinoxylan hydrolyzates as immunomodulators in lipopolysaccharide-induced RAW264.7 macrophages. AB - Inflammation is an important healthy immune response of the body during lesions and infection. However, uncontrolled excessive inflammation can be damaging to the cells. The specific objective of this research was to evaluate the effect of structural details of enzymatically derived wheat arabinoxylan hydrolyzates (AXH) on their immunomodulatory properties. Out of the 30 AXH, six AXH showed statistically significant reduction in NO production compared to the control, causing an approximately 24 to 12% reduction in NO production. Five AXH exhibited statistically significant pro-inflammatory properties in the LPS induced cells, causing an approximately 10 to 14% increase compared to the control. A negative correlation was seen between NO production and total arabinoxylan (AX) * amount of 1,4-linked xylose with arabinose substituted at the O-3 position. Thus, AXH with higher AX and substitution at the O-3 position are favorable candidates to reduce the lipopolysaccharide induced inflammation. These results suggest that there may be a structure-function relationship for these AXH as immunomodulators. PMID- 27359278 TI - Factors Associated With Narcotic Use After Clavicle Fractures. AB - Clavicle fractures are common in adults. Recent studies have shown that operative treatment of clavicle fractures has benefits in many situations. However, there is controversy about the indications. Data on social outcomes are limited. A total of 434 patients with 436 clavicle fractures treated both operatively and nonoperatively at a level 1 trauma center were identified. Narcotic use was recorded 2, 4, 6, 8, 10, 12, 14, and 16 weeks after injury for both treatment groups. Other descriptive data included age, sex, laterality, hand dominance, rib fractures, smoking, alcohol use, employment, long bone or spine fracture, open clavicle fracture, and mechanism of injury. Logistic regression analysis was performed to determine the independent predictors of narcotic use after clavicle fracture. Open reduction and internal fixation was performed in 105 fractures (24%), and 329 fractures were managed nonoperatively. A total of 154 patients (35%) reported some narcotic use 2 weeks after injury, and 15% were still using narcotics 16 weeks after injury. Narcotic use decreased over time in patients treated with open reduction and internal fixation (10% vs 15% after nonoperative management). Patients treated with open reduction and internal fixation reported reduced narcotic use at 16 weeks (odds ratio [OR], 0.454; P=.070). Concurrent rib fracture (OR, 5.668; P<.001), smoking (OR, 3.095; P=.013), unemployment (OR, 5.429; P<.0005), and long bone or spine fracture (OR, 6.761; P<.001) were predictors of narcotic use. Further studies of the social, economic, and financial outcomes of clavicle fracture and osteosynthesis are warranted. [Orthopedics. 2016; 39(5):e917-e923.]. PMID- 27359279 TI - Patient Perceptions of Reimbursement for Arthroscopic Meniscectomy and Anterior Cruciate Ligament Reconstruction. AB - Historically, patient perceptions of surgeon reimbursement have been exaggerated compared with actual reimbursement. There is limited information about patient perceptions of physician reimbursement for arthroscopic meniscectomy and anterior cruciate ligament (ACL) reconstruction. This study evaluated patient perceptions of physician reimbursement for these procedures and compared perceptions of health care reform between urban and suburban clinics. Surveys were given to 231 consecutive patients, and patients were asked how much they believed a surgeon should be reimbursed for arthroscopic meniscectomy and ACL reconstruction as well as their perception of actual Medicare reimbursement to physicians. Patients were then informed of the actual reimbursement rates and asked additional questions about health care reform. Survey responses were compared in an urban setting vs a suburban setting. On average, patients reported that surgeons should receive $8096 for meniscectomy and $11,794 for ACL reconstruction. Patients estimated that Medicare paid physicians $5442 for meniscectomy and $6667 for ACL reconstruction. In addition, 65% of patients believed that reimbursement for meniscectomy was too low, and 57% of patients believed that reimbursement for ACL reconstruction was too low. Fewer than 2% of patients believed that surgeon salaries should be cut, and 75% believed that orthopedic surgeons should be paid more for subspecialty training. No differences were found in patients' perceptions of reimbursement or health care reform between urban and suburban settings. Patients perceived that the values of meniscectomy and ACL reconstruction were substantially higher than current Medicare reimbursement values and that surgeon salaries should not be cut. [Orthopedics. 2016; 39(5):e904-e910.]. PMID- 27359280 TI - Surface Aneurysmal Bone Cyst: Clinical and Imaging Features in 10 New Cases. AB - Aneurysmal bone cyst originating from the surface of the bone, either within the cortex or subperiosteally, is an uncommon anatomic subtype. This article reports the clinical and radiologic evaluations and treatment outcomes of 10 patients with surface aneurysmal bone cysts that were surgically treated between 1982 and 2014. Mean age at the time of surgery was 22.4 years (range, 11-44 years). According to Capanna's radiographic evaluation criteria, 6 of the lesions were classified as type V and 4 were classified as type IV. Radiographically, periosteal shell formation was observed to be complete in 4 patients, partial in 3, and absent in 3, and 6 patients had Codman's angle or buttress formation. In 1 patient, computed tomography scan showed birdcage-like ossification attached to the surface of bone. Magnetic resonance imaging showed fluid-fluid levels in 5 patients. All of the patients had standard curettage and high-speed burr application as an adjuvant. No patient had local recurrence at the end of the follow-up period of 98.4 months (range, 13-288 months). These findings show the importance of careful radiologic evaluation and biopsy to better plan a treatment strategy when surface aneurysmal bone cyst is included in the differential diagnosis. The finding of fluid-fluid levels on magnetic resonance imaging or computed tomography is not pathognomonic for primary aneurysmal bone cyst; however, the absence of this finding does not rule out the diagnosis. The rate of local recurrence after curettage plus high-speed burr is reasonably low, and other adjuvant procedures should be used whenever needed. [Orthopedics. 2016; 39(5):e897-e903.]. PMID- 27359281 TI - Frequency of Recidivism in Patients With Orthopedic Trauma. AB - The goals of this study were to determine the frequency of trauma recidivism and to identify risk factors. The authors hypothesized that substance abuse and mental illness would be associated with recidivism. They performed a retrospective review of 879 patients who were treated surgically for high-energy fractures over a period of 4 years. Recidivism was defined as presentation to the trauma center for a new, unrelated injury. A recurrent recidivist was a repeat patient who returned for more than 1 additional injury. The study identified 164 (18.7%) patients who returned with a new injury. Mean age of recidivists was 37.1 years vs 40.7 years for nonrecidivists (P=.025). Of the recidivists, 80% were male, and this group was more likely to be unmarried (76.2% vs 67.2%, P=.044) and unemployed (40.4% vs 19.6%, P<.0001). Recidivists were also more likely to be uninsured (33.5% vs 17.8%, P<.0001) or to have Medicaid coverage (33.5% vs 23.2%, P<.0001). Recidivists were more likely to have used alcohol (47.2% vs 32.0%, P=.0007) or to be intoxicated (32.4% vs 21.2%, P=.005) and to use tobacco (66.2% vs 50.2%, P=.0003) or recreational drugs (59.1% vs 43.2%, P=.0004) at baseline. The rate of documented mental illness was also higher in repeat patients than in nonrepeat patients (28.1% vs 20.0%, P=.03). These findings showed that recidivism is common, occurring overall in 18.7% of the study sample within a mean of 2.9 years. Factors associated with recidivism included age younger than 40 years, unmarried status, substance use, unemployment, and lack of insurance coverage. The greatest independent risk factors for recidivism were Medicaid insurance or no insurance and a history of a gunshot wound or assault. [Orthopedics. 2016; 39(5):300-306.]. PMID- 27359282 TI - Risk Adjustment for Medicare Total Knee Arthroplasty Bundled Payments. AB - The use of bundled payments is growing because of their potential to align providers and hospitals on the goal of cost reduction. However, such gain sharing could incentivize providers to "cherry-pick" more profitable patients. Risk adjustment can prevent this unintended consequence, yet most bundling programs include minimal adjustment techniques. This study was conducted to determine how bundled payments for total knee arthroplasty (TKA) should be adjusted for risk. The authors collected financial data for all Medicare patients (age>=65 years) undergoing primary unilateral TKA at an academic center over a period of 2 years (n=941). Multivariate regression was performed to assess the effect of patient factors on the costs of acute inpatient care, including unplanned 30-day readmissions. This analysis mirrors a bundling model used in the Medicare Bundled Payments for Care Improvement initiative. Increased age, American Society of Anesthesiologists (ASA) class, and the presence of a Medicare Major Complications/Comorbid Conditions (MCC) modifier (typically representing major complications) were associated with increased costs (regression coefficients, $57 per year; $729 per ASA class beyond I; and $3122 for patients meeting MCC criteria; P=.003, P=.001, and P<.001, respectively). Differences in costs were not associated with body mass index, sex, or race. If the results are generalizable, Medicare bundled payments for TKA encompassing acute inpatient care should be adjusted upward by the stated amounts for older patients, those with elevated ASA class, and patients meeting MCC criteria. This is likely an underestimate for many bundling models, including the Comprehensive Care for Joint Replacement program, incorporating varying degrees of postacute care. Failure to adjust for factors that affect costs may create adverse incentives, creating barriers to care for certain patient populations. [Orthopedics. 2016; 39(5):e911-e916.]. PMID- 27359283 TI - Definitive Treatment of Infected Shoulder Arthroplasty With a Cement Spacer. AB - Infection in the setting of shoulder arthroplasty can result in significant pain, loss of function, and the need for additional surgery. As the use of shoulder arthroplasty increases, the medical and economic burdens of periprosthetic joint infection increase as well. The ideal management of infected shoulder prostheses has not been established. This report describes 9 patients from a single institution who had an infected shoulder arthroplasty that was definitively managed with a cement spacer. All patients had a minimum of 2 years of follow-up. Of the 9 patients in this study, 6 were men. Mean age was 73+/-9 years. Of the study patients, 1 had diabetes, 2 presented with Parkinson's disease, and 5 had a history of tobacco use. Average body mass index was 27.9+/-7 kg/m(2). After mean follow-up of 4 years, none of the patients had clinical or radiographic evidence of infection. Functional outcomes, as measured by American Shoulder and Elbow Surgeons scores, were good or fair in 89% of patients, and the average American Shoulder and Elbow Surgeons score was 57. A review of recent literature suggested that the current findings were similar to those in studies reporting 1- or 2 stage revision procedures. Although cement spacers are typically used as part of a 2-stage revision procedure, the current findings suggest that cement spacers can be used effectively to eradicate infection and allow for acceptable functional recovery and range of motion in patients who have severe medical comorbidities and cannot tolerate additional surgery. [Orthopedics. 2016; 39(5):e924-e930.]. PMID- 27359284 TI - Biological Therapies for Cartilage Lesions in the Hip: A New Horizon. AB - Treatment of hip cartilage disease is challenging, and there is no clear algorithm to address this entity. Biomarkers are arising as promising diagnostic tools because they could play a role in the early assessment of the prearthritic joint and as a prognostic factor before and after treatment. The potential effect of biomarkers may be used to categorize individuals at risk of evolving to severe osteoarthritis, to develop new measures for clinical progression of the disease, and to develop new treatment options for the prevention of osteoarthritis progression. A trend toward a less invasive biological treatment will usher in a new treatment era. With the growth of surgical skills in hip arthroscopy, cartilage restoration techniques are evolving in a fast and exponential manner. Biological and surgical treatments have been proposed to treat these pathologies. Biological treatments include platelet-rich plasma, stem cells or bone marrow aspirate concentration, hyaluronic acid, losartan, and fish oil. Surgical treatments include microfracture alone or augmented, direct repair, autologous chondrocyte implantation, matrix-induced chondrocyte implantation, autologous matrix-induced chondrogenesis, mosaicplasty, osteochondral allograft transplantation, and stem cells implanted in matrix (stem cells in membranes/expanded stem cells). This article reviews new evidence available on treatment options for chondral lesions and early osteoarthritis of the hip. [Orthopedics. 2016; 39(4):e715-e723.]. PMID- 27359285 TI - Intramedullary Nailing of Open Tibial Fractures: Provisional Plate Fixation. AB - Tibia fracture is the most common type of long bone fracture, and intramedullary nailing is the preferred treatment. In open fractures, a provisional plate is often used to maintain reduction. It is unknown whether this practice increases the risk of infection or other complications. This study retrospectively compared patients who were treated at a level 1 trauma center with intramedullary nailing of an open tibia fracture. Patients who were included: (1) were 18 years or older; (2) were treated between January 1, 2005, and June 30, 2013; (3) had an open fracture of the tibia; and (4) were treated operatively with intramedullary nailing, with or without provisional plate fixation. Patient sex, history of diabetes, history of smoking, mechanism of injury, and side of injury were analyzed. Postoperative complications included infection, delayed union or non union, compartment syndrome, and death. After the authors controlled for age, Gustilo-Anderson type, and AO/Orthopaedic Trauma Association classification, they found that provisional plate use did not significantly increase the risk of infection (adjusted odds ratio, 1.64; 95% confidence interval, 0.51-5.32; P=.41) or any other complications (adjusted odds ratio, 1.24; 95% confidence interval, 0.46-3.35; P=.67). In the subgroup of patients who had a provisional plate (n=35), removal of the plate did not significantly decrease the risk of infection (adjusted odds ratio, 0.43; 95% confidence interval, 0.07-2.69; P=.36) or other complications (adjusted odds ratio, 0.55; 95% confidence interval, 0.12-2.46; P=.44). In open tibia fractures treated with intramedullary nailing, provisional plate stabilization, a valuable reduction aid, did not increase the risk of infection or other complications. Because of the small subgroup size, however, definitive conclusions cannot be drawn about removal of these provisional plates. [Orthopedics. 2016; 39(5):e931-e936.]. PMID- 27359286 TI - MicroRNA-210 and its theranostic potential. AB - INTRODUCTION: MicroRNAs (miRNAs) are a set of small single-stranded noncoding RNAs with diverse biological functions. As a prototypical hypoxamir, human microRNA-210 (hsa-miR-210) is one of the most widely studied miRNAs thus far. In addition to its involvement in sophisticated regulation of numerous biological processes, miR-210 has also been shown to be associated with the development of different human diseases including various types of cancers, cardiovascular and cerebrovascular diseases, and immunological diseases. Given its multi-faceted functions, miR-210 may serve as a novel and promising theranostic target for prevention and treatment of diseases. Areas covered: This review aims to provide a comprehensive overview of miR-210, the regulation of its expression, biological functions and molecular mechanisms, with particular emphasis on its diagnostic and therapeutic potential. Expert opinion: Although the exact roles of miR-210 in various diseases have not been fully clarified, targeting miR-210 may be a promising therapeutic strategy. Further investigations are also needed to facilitate therapeutic-clinical applications of miR-210 in human diseases. PMID- 27359289 TI - REDUCING HOSPITAL RE-ADMISSIONS IN PATIENTS WITH DIABETES: DEVELOPING BETTER STRATEGIES. PMID- 27359287 TI - EVALUATION OF TOTAL DAILY DOSE AND GLYCEMIC CONTROL FOR PATIENTS TAKING U-500 REGULAR INSULIN ADMITTED TO THE HOSPITAL. AB - OBJECTIVE: Patients using U-500 regular insulin are severely insulin resistant, requiring high doses of insulin. It has been observed that a patient's insulin requirements may dramatically decrease during hospitalization. This study sought to systematically investigate this phenomenon. METHODS: We performed a retrospective chart review of patients with U-500 insulin outpatient regimens who were admitted to the San Antonio Military Medical Center over a 5-year period. Each patient's outpatient total daily dose (TDD) of insulin was compared to the average inpatient TDD. The outpatient estimated average glucose (eAG) was calculated from the glycated hemoglobin (HbA1c) and compared to the average inpatient glucose. RESULTS: There were 27 patients with a total of 62 separate admissions. The average age was 64.4 years, with a mean body mass index of 38.9 kg/m2 and eAG of 203 mg/dL (HbA1c, 8.7%, 71.6 mmol/mol). All patients were converted from U-500 to U-100 upon admission. The average inpatient TDD of insulin was 91 units, versus 337 units as outpatients (P<.001). Overall, 89% of patients received <=50% of their outpatient TDD. The average inpatient glucose was slightly higher than the outpatient eAG, 234 mg/dL versus 203 mg/dL (P = .003). CONCLUSION: U-500 insulin is prone to errors in the hospital setting, so conversion to U-100 insulin is a preferred option. Despite a significant reduction in insulin TDD, these patients had clinically similar glucose levels. Therefore, patients taking U-500 insulin as an outpatient can be converted to a U 100 basal-bolus regimen with at least a 50% reduction of their outpatient TDD. ABBREVIATIONS: BG = blood glucose eAG = estimated average glucose HbA1c = glycated hemoglobin NPO = nil per os SPSS = Statistical Package for the Social Sciences TDD = total daily dose. PMID- 27359291 TI - CARDIAC STRUCTURAL AND FUNCTIONAL ABNORMALITIES IN FEMALES WITH UNTREATED HYPOPITUITARISM DUE TO SHEEHAN SYNDROME: RESPONSE TO HORMONE REPLACEMENT THERAPY. AB - OBJECTIVE: Data on cardiac abnormalities in females with untreated hypopituitarism are limited. We investigated echocardiographic abnormalities in females with untreated hypopituitarism and their response to treatment. METHODS: Twenty-three females with treatment-naive hypopituitarism and 30 matched healthy controls were evaluated for cardiac structure and function. Echocardiographic evaluation was done at presentation and after achieving a euthyroid and eucortisol state. RESULTS: Fourteen (61%) patients had mitral regurgitation, and 11 (48%) had pericardial effusion as against none among controls. Indices of left ventricular (LV) size like LV end diastolic dimension (LVEDD; 44.5 +/- 3.5 mm in cases vs. 47.6 +/- 3.8 mm in controls, P = .004), and LV diastolic volume (LVEDV; 91.8 +/- 18.0 mL versus 106.5 +/- 20.4 mL, P = .009) were significantly lower in the SS group compared with controls. LV mass (LVM) was 70.8 +/- 19.2 g in cases and 108.0 +/- 33.2 g in controls (P = .02). Similarly, indices of LV systolic function like stroke volume (SV; 59.1 +/- 12.0 mL in cases and 74.4 +/- 15.8 mL in controls; P = .000), ejection fraction (EF; 64.3 +/- 6.2 % in cases against 69.9 +/- 9.2 % in controls; P = .03), and fractional shortening (FS; 34.9 +/- 4.7% versus 40.1 +/- 4.4%, P = .000) were significantly decreased in patients compared with controls. Cardiac abnormalities normalized with restoration of a euthyroid and eucortisol state. CONCLUSION: Pericardial effusion, mitral regurgitation, and diminished LVM are common in females with untreated hypopituitarism. ABBREVIATIONS: ACTH = adrenocorticotrophic hormone BMI = body mass index DT = deceleration time EDV = end-diastolic volume EF = ejection fraction FS = fractional shortening GH = growth hormone IGF-1 = insulin growth factor-1 ITT = insulin tolerance test IVSd = interventricular septal diameter LH = luteinizing hormone LV = left ventricular LVEDD = LV end diastolic dimension LVEDV = LV end diastolic volume LVM = LV mass MRI = magnetic resonance imaging MVP = mitral value prolapse PPH = postpartum hemorrhage PWd = posterior wall diameter SS = Sheehan syndrome SV = stroke volume T3 = triiodothyronine T4 = thyroxine TSH = thyroid-stimulating hormone. PMID- 27359292 TI - ASYMMETRIC DIMETHYLARGININE LEVELS AND ATHEROSCLEROSIS MARKERS IN CUSHING SYNDROME. AB - OBJECTIVE: As a consequence of hypercortisolism, Cushing syndrome (CS) is frequently observed with other diseases that are associated with atherosclerosis, including diabetes mellitus, dyslipidemia, hypertension, and obesity. Cardiovascular disease (CVD) is the primary cause of mortality and morbidity in CS. We investigate CVD risk markers such as asymmetric dimethylarginine (ADMA), lipoprotein-associated phospholipase A2 (Lp-PLA2), highsensitive C-reactive protein (hsCRP), homocysteine, lipid levels, ankle-brachial index (ABI), and carotid intimamedia thickness (CIMT) in CS. METHODS: Our study included 27 patients with CS and 27 age-, sex-, body mass index (BMI)-, and comorbid disease matched control subjects. RESULTS: Plasma ADMA levels were significantly lower in the CS group than the control group (P = .013). Total cholesterol, low-density lipoprotein, triglycerides, high-density lipoprotein, and apolipoprotein A1 and apolipoprotein B levels were higher in patients with CS than the control group (P<.05). We did not find any statistically significant differences in levels of hsCRP, Lp-PLA2, or homocysteine or CIMT and ABI measurements between the CS group and comorbidity-matched control group (P>.05). CONCLUSION: We found that ADMA levels were lower in CS, the finding that should be further investigated. Levels of hsCRP, Lp-PLA2, and homocysteine levels and CIMT and ABI measurements were similar between the CS group and comorbidity-matched control group. None of these markers was prominent to show an increased risk of CVD in CS, independent of the comorbidities of CS. ABBREVIATIONS: ABI = ankle-brachial index Apo = apolipoprotein ADMA = asymmetric dimethylarginine BMI = body mass index CVD = cardiovascular disease CIMT = carotid intima-media thickness CS = Cushing syndrome DM = diabetes mellitus DDAH = dimethylarginine dimethylaminohydrolase ELISA = enzyme-linked immunosorbent assay HDL = high-density lipoprotein hsCRP = high-sensitive C-reactive protein HOMA-IR = homeostatic model assessment of insulin resistance HT = hypertension LDL = low-density lipoprotein Lp-PLA2 = lipoprotein-associated phospholipase A2 Lp-a = lipoprotein a NO = nitric oxide. PMID- 27359293 TI - USE OF METFORMIN IN CLINICAL ENDOCRINOLOGY. AB - ABBREVIATIONS: CKD = chronic kidney disease DM = diabetes mellitus eGFR = estimated glomerular filtration rate FDA = Food & Drug Administration. PMID- 27359294 TI - Physical Activity Prescription: A Critical Opportunity to Address a Modifiable Risk Factor for the Prevention and Management of Chronic Disease: A Position Statement by the Canadian Academy of Sport and Exercise Medicine. PMID- 27359295 TI - Return to Sport After Anterior Cruciate Ligament Reconstruction in the Skeletally Immature Athlete. AB - OBJECTIVE: Determine the percentage of skeletally immature athletes returning to sports after anterior cruciate ligament (ACL) injury and reconstruction. DESIGN: Retrospective case series. SETTING: Boston Children's Hospital Division of Sports Medicine. PATIENTS: Eligible participants were identified by chart review. Males and females aged <=14 year old who were greater than 2 years after ACL reconstruction surgery seen between January 2001 and May 2009. A total of 250 patients completed the questionnaires. ASSESSMENT OF RISK FACTORS: Age, sex, mechanism, and sport played at time of ACL injury. MAIN OUTCOME MEASURES: Response to the survey was 75% (250 of 333) which was analyzed using descriptive statistics to provide a summary of the study cohort. Kaplan-Meier survivorship analysis was applied to determine time to return to sports participation after ACL reconstruction with Greenwood formula used to calculate 95% confidence intervals around the estimated percentage returning at 6, 9, 12, 18, and 24-month follow-up. RESULTS: After undergoing ACL reconstruction, 96% of skeletally immature athletes are able to return to sports at the same skill level. Median time to return to sports was 9 months postoperative, with most athletes returning to sports (85%) by 12 months. CONCLUSIONS: After undergoing ACL reconstruction, most child athletes are able to return to sports and 50% of these athletes return within 9 months after surgery. CLINICAL RELEVANCE: After undergoing ACL reconstruction, 96% of athletes <=14 year old are able to return to sports at the same skill level. Median time to return to sports was 9 months postoperative, with most athletes returning to sports (85%) by 12 months. In our study, patients cited physical limitation, loss of interest in sport, and fear of reinjury as reasons for not returning to previous level of sport. Return to sport may be improved by additional research into sports-specific training and rehabilitation in this cohort. PMID- 27359296 TI - In Response to: American Professional Football Concussions During the 2013 to 2014 Season. PMID- 27359297 TI - Smart Clothing is the Best Protection Against Zika During Rio Olympic and Paralympic Games. PMID- 27359299 TI - Unbiased Sunlight-Driven Artificial Photosynthesis of Carbon Monoxide from CO2 Using a ZnTe-Based Photocathode and a Perovskite Solar Cell in Tandem. AB - Solar fuel production, mimicking natural photosynthesis of converting CO2 into useful fuels and storing solar energy as chemical energy, has received great attention in recent years. Practical large-scale fuel production needs a unique device capable of CO2 reduction using only solar energy and water as an electron source. Here we report such a system composed of a gold-decorated triple-layered ZnO@ZnTe@CdTe core-shell nanorod array photocathode and a CH3NH3PbI3 perovskite solar cell in tandem. The assembly allows effective light harvesting of higher energy photons (>2.14 eV) from the front-side photocathode and lower energy photons (>1.5 eV) from the back-side-positioned perovskite solar cell in a single photon excitation. This system represents an example of a photocathode photovoltaic tandem device operating under sunlight without external bias for selective CO2 conversion. It exhibited a steady solar-to-CO conversion efficiency over 0.35% and a solar-to-fuel conversion efficiency exceeding 0.43% including H2 as a minor product. PMID- 27359300 TI - Association Equilibrium for Cross-Associating Chains in a Good Solvent: Crowding and Other Nonideality Effects. AB - Association equilibrium has been studied by molecular dynamics (MD) for mixtures of cross-associating molecules (n-decamer+p-dimer and n-decamer+p-decamer) in a good solvent. Each monomer of n-decamers carries an associative site (n-sticker); each molecule of the second component contains two terminal associative sites (p stickers). To model the univalent association between the n-sticker and the p sticker, a technique based on introduction of dummy atoms has been used. We report MD data on the effects of temperature, chain flexibility, and location of the sticker within the chain on the association equilibrium. We find that the presence of nonassociating monomer units of p-chain has a substantial effect on the association equilibrium. This effect is similar to "crowding" in reactive mixtures known to be caused by the presence of inert molecules. Widely used mean field theories of associating chains (e.g., SAFT or Semenov-Rubinstein theory) do not account for the effect of crowding caused by the inert fragments of reactive chains. We introduce simple empirical corrections for crowding that describe association equilibrium in the presence of nonassociating fragment in a chain like molecule. PMID- 27359298 TI - Actin polymerization-dependent activation of Cas-L promotes immunological synapse stability. AB - The immunological synapse formed between a T-cell and an antigen-presenting cell is important for cell-cell communication during T-cell-mediated immune responses. Immunological synapse formation begins with stimulation of the T-cell receptor (TCR). TCR microclusters are assembled and transported to the center of the immunological synapse in an actin polymerization-dependent process. However, the physical link between TCR and actin remains elusive. Here we show that lymphocyte specific Crk-associated substrate (Cas-L), a member of a force sensing protein family, is required for transport of TCR microclusters and for establishing synapse stability. We found that Cas-L is phosphorylated at TCR microclusters in an actin polymerization-dependent fashion. Furthermore, Cas-L participates in a positive feedback loop leading to amplification of Ca2+ signaling, inside-out integrin activation, and actomyosin contraction. We propose a new role for Cas-L in T-cell activation as a mechanical transducer linking TCR microclusters to the underlying actin network and coordinating multiple actin-dependent structures in the immunological synapse. Our studies highlight the importance of mechanotransduction processes in T-cell-mediated immune responses. PMID- 27359301 TI - Interactive effect of negative affectivity and anxiety sensitivity in terms of mental health among Latinos in primary care. AB - From a public health perspective, primary care medical settings represent a strategic location to address mental health disapirty among Latinos. Yet, there is little empirical work that addresses affective vulnerability processes for mental health problems in such settings. To help address this gap in knowledge, the present investigation examined an interactive model of negative affectivity (tendency to experience negative mood states) and anxiety sensitivity (fear of the negative consequences of aversive sensations) among a Latino sample in primary care in terms of a relatively wide range of anxiety/depression indices. Participants included 390 Latino adults (Mage=38.7, SD=11.3; 86.9% female; 95.6% reported Spanish as first language) from a primary care health clinic. Primary dependent measures included depressive, suicidal, social anxiety, and anxious arousal symptoms, number of mood and anxiety disorders, and disability. Consistent with prediction, the interaction between negative affectivity and anxiety sensitivity was significantly related to suicidal, social anxiety, and anxious arousal symptoms, as well as number of mood/anxiety diagnoses and disability among the primary care Latino sample. The form of the interactions indicated a synergistic effect, such that the greatest levels of each outcome were found among those with high negative affectivity and high anxiety sensitivity. There was a trending interaction for depressive symptoms. Overall, these data provide novel empirical evidence suggesting that there is a clinically relevant interplay between anxiety sensitivity and negative affectivity in regard to the expression of anxiety and depressive symptoms among a Latino primary care sample. PMID- 27359302 TI - Elevated levels of Hs-CRP and IL-6 after delivery are associated with depression during the 6 months post partum. AB - The objective of this study is to determine whether inflammatory markers (high sensitivity C-reactive protein (Hs-CRP) and interleukin (IL)-6) early in the postpartum period contribute to the development of postpartum depression (PPD). From 4 May 2014 to 30 June 2014, all eligible women not on medication for depression giving birth at the Beijing Chao-Yang hospital were consecutively recruited and followed up for 6 months. Depression symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS), and inflammatory biomarkers (Hs CRP and IL-6) were tested. During the study period, 296 women were enrolled and completed follow-up. In these women, 45 (15.2%) were considered as meeting the criteria for PPD. Serum levels of Hs-CRP and IL-6 in women with PPD were significantly higher than those without PPD (all P<0.0001). Receiver operating characteristics to predict PPD demonstrated areas under the curve of IL-6 of 0.861 (95% confidence interval (CI), 0.801-0.922), which was superior to Hs-CRP (0.837 (95% CI, 0.781-0.894), P<0.01). In multivariate logistic regression analysis, IL-6 and Hs-CRP were independent predictors of PPD. The present study demonstrates a strong relationship between elevated serum Hs-CRP and IL-6 levels at admission and the development of PPD within 6 months. PMID- 27359303 TI - When attachment anxiety impedes support provision: The role of feeling unvalued and unappreciated. AB - Two studies examined whether concerns of relational value interfere with the ability of individuals higher in attachment anxiety to provide responsive support to their partner. In both studies, heterosexual couples engaged in 2 video recorded discussions about each other's most important personal goal. Support recipients (the person whose goal was discussed) reported on how distressed they felt during the discussion. Support providers (the partner who was in the position to provide support) reported on how valued and appreciated they felt during the discussion. Independent observers coded the degree to which support providers exhibited critical and derogating behaviors versus warmth and understanding during the discussion. The results were consistent across both studies, with the exception that the predicted effects only emerged for male providers in Study 2. First, more anxious support providers felt less valued and appreciated when support recipients reported greater distress. Second, lower feelings of value/appreciation were associated with more anxious providers exhibiting greater negative support behavior. These results illustrate how the concerns of relational value central to attachment anxiety impede effective support provision, which should have detrimental effects for relationships. Indeed, consistent with prior research, greater negative behaviors by support providers predicted declines in recipients' relationship quality over time. (PsycINFO Database Record PMID- 27359304 TI - [One quarter of all readmissions are avoidable]. PMID- 27359305 TI - [Early adrenaline in patients with shockable rhythm is disadvantageous]. PMID- 27359306 TI - [Acute gastrointestinal bleeding]. PMID- 27359307 TI - [Good results after transcatheter aortic-valve replacement in patients with intermediate risk]. PMID- 27359308 TI - [68-year old woman with B-symptomatology and pelvic pain]. PMID- 27359309 TI - [Pacemaker for innovations]. PMID- 27359310 TI - [Long-term-management of organ transplant recipients]. AB - Due to advances in immunosuppressive therapy and surgical techniques, survival rates after solid organ transplantation have constantly improved over the last decades. In long-term care after transplantation, physicians need to focus as much on diagnosis and treatment of allograft-related complications as they should consider comorbidities and evaluate risk-factors and adverse events of immunosuppressive agents to prevent secondary diseases. In particular, cardiovascular and metabolic diseases, malignancy and infection play a major role in long-term survival. Therefore, screening of organ transplant recipients in regard to these complications and adverse events is a crucial part of follow up in these patients. PMID- 27359311 TI - [Ultrasound of livertransplants]. AB - The overall long-term survival rate of liver transplant patients is 70-75 %. During the early stages, the complications are vascular in nature, and in the later stages, biliary complications are major causes of morbidity. With the help of sonography, in particular with the addition of contrast enhanced ultrasound, a reliable diagnosis is possible. Despite this, in individual cases, other additional imaging methods should still be employed. The therapy should be used exclusively by interventional gastroentologists, radiologists or surgeons. PMID- 27359312 TI - [Acute liver failure after ingestion of death cap mushrooms]. AB - Amatoxins, which are mainly found in Amanita phalloides, Amanita virosa, and Galerina autumnalis, are responsible for the majority of fatal intoxication with green death cap. The intoxication is associated with acute liver failure, which explains the poor prognosis. Acute liver injury is generally preceeded by a gastrointestinal phase with nausea, vomiting and diarrhea. In the course, pre renal kidney failure due to the associated fluid deficit and fulminant liver failure may occur. General guidelines for the treatment of amatoxin poisoning are yet not available. We report on three patients who suffered from amatoxin mushroom poisoning after ingestion of green death cap mushrooms. Based on the pathophysiology of amatoxin poisoning, we discuss a potential therapeutic approach. PMID- 27359313 TI - [Duplex ultrasound of deep vein thrombosis of the leg]. AB - Colour coded Duplex ultrasound is the diagnostic tool of choice in case of suspicion of a deep vein thrombosis of the leg. In the hand of an experienced examiner a thrombosis can be confirmed or excluded, but also differential diagnoses can be detected. In this article we show you how to perform a systematic ultrasound examination of the leg veins. PMID- 27359314 TI - [Desoxypipradrol - a new (already well known) designer drug]. AB - Novel psychoactive substances (NPS) are easily accessible and the consumption has increased in recent years. New compounds as well as compounds derived from pharmaceutical research or the patent literature are provided, mostly without any declaration. As a consequence, severe adverse reactions may occur after consumption of unknown doses of these drugs, in particular after mixed intake of different psychoactive substances or co-medication. The toxic effects in such cases are not predictable. We report cases of rhabdomyolysis in patients after consumption of desoxipipradrol in combination with other NPS. Particularly in case of synergistic serotonergic effects a distinct stimulation of 5-HT2A receptors (or 5-HT1A-receptors) should be considered which may lead to serotonergic syndrome. PMID- 27359315 TI - [Anaemia in the elderly]. AB - In the elderly, even mild anaemia leads to significantly decreased quality of life and reduced survival rate. Therefore even mild anaemias should be worked up especially in the elderly. More than 75 % of all anaemias have a specific and treatable cause.Differential diagnosis of anaemia in the elderly is much more challenging compared to the differential diagnosis in younger patients: in older patients often more than one dysfunction is responsible for the anaemia simultaneously. Many routine laboratory parameters are changed by ageing and are therefore only of limited value for diagnosis of anaemia. Soluble transferinreceptor and hepcidin are two parameters feasible for differential diagnosis of the causes of anaemia in the elderly.The most common cause of iron deficiency anaemia in the elderly is gastrointestinal bleeding. Many causes for gastrointestinal bleeding -like angiodysplasia of the colon - can readily be treated with endoscopic therapy. For this reason, colonoscopy is part of the standard workup for elderly patients with iron-deficient anaemia (IDA) if no contraindications exist.Therapy of anaemia is based on the specific cause or the causes. In IDA, the first step other than causal treatment is to replace iron orally. If this is not tolerated because of side effects or does not lead to a sufficient rise in the haemoglobin level, intravenous iron replacement therapy is indicated. Folic acid deficiency is generally treated orally, whereas vitamin B12 deficiency is generally treated by the parenteral - preferably subcutaneous - route. In anaemia due to chronic renal failure and anaemia due to myelodysplastic syndromes, the underlying cause must be treated, furthermore erythropoiesis stimulating agents can be indicated. PMID- 27359316 TI - [Glomerulonephritis]. AB - Glomerulonephritis encompasses a group of diseases that are characterized by inflammatory glomerular processes and clinically usually present with a nephritic and / or a nephrotic syndrome, as well as a deterioration of the renal function. Often, the diseases are accompanied by arterial hypertension and severe edema. In many cases however, the clinical symptoms are very mild or missing in the early phase of disease and therefore lead to a delayed diagnosis only after an impairment of renal function has developed. Urinalysis shows abnormalities in the very early phases of glomerulonephritis and should be performed in all patients, as soon as any evidence of renal involvement is present. Glomerulonephritis may occur primarily in the glomeruli, or present as renal involvement in the context of systemic diseases, most often vasculitis. In some cases, a symptomatic therapy is sufficient, while in other patients, a glomerulonephritis may represent as a medical emergency, which should be immediately and aggressively treated in order to prevent loss of renal function. Here we summarize the most important entities of glomerulonephritis, focusing on the pathogenesis, diagnostic tools and treatment options. The primary goal is the early diagnosis and a targeted, effective treatment of these patients. PMID- 27359317 TI - [How dangerous is the Zika virus?]. AB - The Zika virus (ZIKV) may cause microcephaly and other serious birth defects. Due to a lack of epidemiological data, the teratogenic risk is unknown. The upcoming Olympic Games in Rio may cause it to spread to unprepared countries with underdeveloped healthcare systems. ZIKV is also sexually transmitted. The pathogenesis of sexual transmission and the duration of contagiousness are currently unknown. To minimize the risks caused by the Olympic Games in Rio, developing and emerging nations must be supported in disease prevention by the WHO and industrialized nations. In addition, the pathogenesis and risks of sexual ZIKV transmission require thorough investigation. PMID- 27359318 TI - [Burnout syndrome - Retaining your mental balance]. PMID- 27359319 TI - [The use of benzodiazepines and Z-drugs for patients with sleeping problems - A survey among hospital doctors and nurses]. AB - Aim | Benzodiazepines and Z-drugs are frequently prescribed sleep medications in spite of their poor risk-benefit ratio when used over a longer period of time. The aim of the study was to find out how the medical and nursing staff in a general hospital estimated the frequency of use for these drugs, and the risk benefit ratio for elderly patients as well as the factors which positively influence the perceived use of these drugs. Methods | All members of the medical and nursing staff of a hospital received a questionnaire about their use of, and attitudes towards, benzodiazepines and Z-drugs. Absolute and relative frequencies were calculated to estimate the perceived frequency of use and the risk-benefit ratio. Multiple logistic regressions were used to analyze which factors are associated with a perceived high use of benzodiazepines or Z-drugs for insomnia. Results | More nurses than hospital doctors believed that they dispensed benzodiazepines often or always (57 % vs. 29 %) to patients with insomnia; this was also the case for Z-drugs (66 % vs. 29 %). Nearly half of the hospital doctors and 29 % of the nurses perceived more harms than benefits for benzodiazepines in the elderly. The following factors were associated with a high perceived usage of Z-drugs: working as a nurse (OR: 13,95; 95%-CI: 3,87-50,28), working in a non-surgical department (5,41; 2,00-14,61), having < 5 years of professional experience (4,90; 1,43-16,81) and feeling that the benefits of Z drugs outweigh the risks for elderly patients (5,07; 1,48-17,35). For benzodiazepines, only the perceived positive risk-benefit ratio had an influence on the perceived use (3,35; 1,28-8.79). Conclusion | The medical and nursing staff perceived the frequency of prescription of benzodiazepines and Z-drugs and the risk-benefit ratio in different ways. Other aspects, such as working in a non surgical department or having a smaller amount of working experience may also influence the decision to use Z-drugs. PMID- 27359320 TI - Impacts of poultry vaccination on viruses of wild bird. AB - Spillover of viruses from farmed poultry into wild birds is a relatively new area of study at the livestock-wildlife interface. These transmission events can threaten the health of wild birds. There is growing evidence of transmission of vaccine viruses from poultry to wild birds, including attenuated vaccine strains of Newcastle disease virus and infectious bronchitis virus, and also spread of virulent viruses that may have evolved under the pressure of vaccine use, such as Marek's disease virus. Viral contaminants of poultry vaccines, including reticuloendotheliosis virus, may also be transmitted to wild birds and result in disease. New, vectored vaccines are less likely to directly spread to wild birds but this risk may rise as a result of recombination. PMID- 27359321 TI - "You get to know the people and whether they're talking sense or not": Negotiating trust on health-related forums. AB - The internet is increasingly being used as a source of health advice and information by individuals with long term conditions (LTCs). Specifically, online forums allow people to interact with others with similar conditions. However, it is not clear how online health information is assessed by those with LTCs. This study aims to address this gap by exploring how individuals with contested and uncontested LTCs utilise internet forums. Semi-structured interviews were conducted with 20 participants with ME/CFS and 21 participants with type 1 and 2 diabetes and analysed using thematic analysis. Participants were recruited via online and offline routes, namely forums, email lists, newsletters, and face-to face support groups. The findings indicate that the use of online forums was a complex and nuanced process and was influenced by a number of individual and illness-specific factors. Participants trusted those with similar experiences and perspectives as themselves, while also valuing conventional biomedical information and advice. By accessing support online, forum users were able to draw on a personalised form of support based on the lived experiences of their peers. However, the role of digital literacy in developing and maintaining online relationships must be acknowledged. PMID- 27359322 TI - Happiness and health across the lifespan in five major cities: The impact of place and government performance. AB - RATIONALE: A growing body of research suggests that urban design has an effect on health and well-being. There have been very few studies to date, however, that compare these effects across the lifespan. OBJECTIVE: The current study examines the direct and indirect effects of the city environment on happiness. It was hypothesised that citizens' ratings of their city along dimensions of performance (e.g., basic - usually government - services related to education, healthcare, social services, and policing) and place (e.g., the beauty of the city and a built environment that provides access to cultural, sport, park, transport, and shopping amenities) would be significant predictors of happiness but that the nature of these effects would change over the lifespan. METHODS: 5000 adults aged 25-85 years old living in Berlin, Paris, London, New York, and Toronto completed the Quality of Life Survey in 2007. Respondents reported their happiness levels and evaluated their city along place and performance dimensions. RESULTS: The results of the study demonstrate an interesting, and complex relationship between the city environment and happiness of residents across the lifespan. Findings suggest that the happiness of younger residents is a function of having easy access to cultural, shopping, transport, parks and sport amenities and the attractiveness of their cities (i.e. place variables). The happiness of older residents is associated more with the provision of quality governmental services (i.e., performance variables). Place and performance variables also have an effect on health and social connections, which are strongly linked to happiness for all residents. CONCLUSION: Younger adults' happiness is more strongly related to the accessibility of amenities that add to the quality of a city's cultural and place characteristics; older adults' happiness is more strongly related to the quality of services provided within a city that enable residents to age in place. These results indicate that, in order to be all things to all people, cities should emphasize quality services (e.g., good policing, schools, healthcare access), beauty and character, and provide easy access to transport amenities and cultural and recreational opportunities. PMID- 27359323 TI - The inhibition of UDP-glucuronosyltransferases (UGTs) by vitamin A. AB - 1. The exposed level of vitamin A in plasma might be exceeded due to the both inadvertent and clinical utilization. The adverse effects of vitamin A have been frequently reported, however, the mechanism remains unclear. The inhibition of vitamin A on the activity of UDP-glucuronosyltransferases (UGTs) was determined using in vitro incubation system to explain the adverse effects of vitamin A from a new perspective. 2. UGT supersomes catalyzed glucuronidation of 4 methylumbelliferone (4-MU), trifluoperazine (TFP), and cotinine was used as the probe reaction to evaluate the inhibition of vitamin A toward UGT isoforms, and 100 MUM of vitamin A significantly inhibited the activity of all the tested UGT isoforms. Vitamin A exerted competitive inhibition on the activity of UGT1A1, 2B4, 2B7, and 2B15, and the inhibition kinetic parameters (Ki) were calculated to be 31.1, 16.8, 2.2, and 11.6 MUM for UGT1A1, 2B4, 2B7, and 2B15. In silico docking method was used to try to elucidate the inhibition mechanism of vitamin A toward UGT2B7. The results showed the significant contribution of hydrogen bonds and hydrophobic interaction on the UGT2B7 inhibition by vitamin A. 3. The present study provides a new perspective for the adverse effects of vitamin A through reporting the inhibition of vitamin A on the activity of important phase II drug metabolizing enzymes UGTs, which benefits our deep understanding of mechanism of vitamin A's adverse effects when high exposure of vitamin A occurs. PMID- 27359324 TI - Correction: An Analysis of Costs and Health Co-Benefits for a U.S. Power Plant Carbon Standard. AB - [This corrects the article DOI: 10.1371/journal.pone.0156308.]. PMID- 27359326 TI - Energy Transfer with Semiconductor Quantum Dot Bioconjugates: A Versatile Platform for Biosensing, Energy Harvesting, and Other Developing Applications. AB - Luminescent semiconductor quantum dots (QDs) are one of the more popular nanomaterials currently utilized within biological applications. However, what is not widely appreciated is their growing role as versatile energy transfer (ET) donors and acceptors within a similar biological context. The progress made on integrating QDs and ET in biological configurations and applications is reviewed in detail here. The goal is to provide the reader with (1) an appreciation for what QDs are capable of in this context, (2) how this field has grown over a relatively short time span, and, in particular, (3) how QDs are steadily revolutionizing the development of new biosensors along with a myriad of other photonically active nanomaterial-based bioconjugates. An initial discussion of QD materials along with key concepts surrounding their preparation and bioconjugation is provided given the defining role these aspects play in the QDs ability to succeed in subsequent ET applications. The discussion is then divided around the specific roles that QDs provide as either Forster resonance energy transfer (FRET) or charge/electron transfer donor and/or acceptor. For each QD-ET mechanism, a working explanation of the appropriate background theory and formalism is articulated before examining their biosensing and related ET utility. Other configurations such as incorporation of QDs into multistep ET processes or use of initial chemical and bioluminescent excitation are treated similarly. ET processes that are still not fully understood such as QD interactions with gold and other metal nanoparticles along with carbon allotropes are also covered. Given their maturity, some specific applications ranging from in vitro sensing assays to cellular imaging are separated and discussed in more detail. Finally a perspective on how this field will continue to evolve is provided. PMID- 27359325 TI - Predictors of Increased Risk of Hepatocellular Carcinoma in Patients with Type 2 Diabetes. AB - Epidemiological data indicate that type 2 diabetes is associated with increased risk of hepatocellular carcinoma (HCC). However, risk stratification for HCC has not been fully elucidated in diabetic population. The aim of this study was to identify potential predictors of HCC in diabetic patients without chronic viral hepatitis. A cohort of 3,544 diabetic patients without chronic viral hepatitis or alcoholic cirrhosis was established and subjects were randomly allocated into a derivation and a validation set. A scoring system was developed by using potential predictors of increased risk of HCC from the Cox proportional hazards model. The performance of the scoring system was tested for validation by using receiver operating characteristics analysis. During median follow-up of 55 months, 36 cases of HCC developed (190 per 100,000 person-years). The 5- and 10 year cumulative incidences of HCC were 1.0%, and 2.2%, respectively. Multivariate Cox regression analysis showed that age > 65 years, low triglyceride levels and high gamma-glutamyl transferase levels were independently associated with an increased risk of HCC. DM-HCC risk score, a weighted sum of scores from these 3 parameters, predicted 10-year development of HCC with area under the receiver operating characteristics curve of 0.86, and discriminated different risk categories for HCC in the derivation and validation cohort. In conclusion, old age, low triglyceride level and high gamma-glutamyl transferase level may help to identify individuals at high risk of developing HCC in diabetic patients without chronic viral hepatitis or alcoholic cirrhosis. PMID- 27359327 TI - Associations between diurnal cortisol patterns and lifestyle factors, psychotic symptoms, and neurological deficits: A longitudinal study on patients with chronic schizophrenia. AB - The present study examined the relationships between diurnal cortisol patterns and perceived stress, lifestyle factors, psychotic symptoms, neurological deficits, and daily functioning in patients with chronic schizophrenia. The participants were 149 Chinese patients with chronic schizophrenia, who provided salivary cortisol measures upon waking, before lunchtime, and before bedtime at baseline (Time 1). Self-report measures on perceived stress and lifestyle factors such as body-mass index and daily exercise span were recorded at Time 1. Diagnostic assessments on psychotic symptoms, neurological deficits, and daily functioning were made at Time 1 and Time 2 (3 months later). Latent growth modeling and path modeling analysis were performed to investigate the diurnal cortisol patterns and the relationships with the study variables, respectively. Greater perceived stress and body-mass index and less physical activity were significantly linked to reduced cortisol decline. Reduced cortisol decline at Time 1 significantly predicted greater psychotic (positive and negative) symptoms and more severe neurological deficits in motor coordination and sequencing of complex motor acts at Time 2. The present results contribute to a better understanding of the diurnal cortisol patterns among chronic schizophrenia patients and the associations with lifestyle factors, psychotic symptoms, and neurological deficits. The findings lend support to the neural diathesis-stress model and suggest that hypothalamic-pituitary-adrenal axis may potentially mediate the effects of lifestyle factors on psychotic symptoms and neurological deficits. PMID- 27359328 TI - The Contribution of Numerical Magnitude Comparison and Phonological Processing to Individual Differences in Fourth Graders' Multiplication Fact Ability. AB - Although numerical magnitude processing has been related to individual differences in arithmetic, its role in children's multiplication performance remains largely unknown. On the other hand, studies have indicated that phonological awareness is an important correlate of individual differences in children's multiplication performance, but the involvement of phonological memory, another important phonological processing skill, has not been studied in much detail. Furthermore, knowledge about the relative contribution of above mentioned processes to the specific arithmetic operation of multiplication in children is lacking. The present study therefore investigated for the first time the unique contributions of numerical magnitude comparison and phonological processing in explaining individual differences in 63 fourth graders' multiplication fact ability (mean age = 9.6 years, SD = .67). The results showed that children's multiplication fact competency correlated significantly with symbolic and nonsymbolic magnitude comparison as well as with phonological short term memory. A hierarchical regression analysis revealed that, after controlling for intellectual ability and general reaction time, both symbolic and nonsymbolic magnitude comparison and phonological short-term memory accounted for unique variance in multiplication fact performance. The ability to compare symbolic magnitudes was found to contribute the most, indicating that the access to numerical magnitudes by means of Arabic digits is a key factor in explaining individual differences in children's multiplication fact ability. PMID- 27359329 TI - Mimp/Mtch2, an Obesity Susceptibility Gene, Induces Alteration of Fatty Acid Metabolism in Transgenic Mice. AB - OBJECTIVE: Metabolic dysfunctions, such as fatty liver, obesity and insulin resistance, are among the most common contemporary diseases worldwide, and their prevalence is continuously rising. Mimp/Mtch2 is a mitochondrial carrier protein homologue, which localizes to the mitochondria and induces mitochondrial depolarization. Mimp/Mtch2 single-nucleotide polymorphism is associated with obesity in humans and its loss in mice muscle protects from obesity. Our aim was to study the effects of Mimp/Mtch2 overexpression in vivo. METHODS: Transgenic mice overexpressing Mimp/Mtch2-GFP were characterized and monitored for lipid accumulation, weight and blood glucose levels. Transgenic mice liver and kidneys were used for gene expression analysis. RESULTS: Mimp/Mtch2-GFP transgenic mice express high levels of fatty acid synthase and of beta-oxidation genes and develop fatty livers and kidneys. Moreover, high-fat diet-fed Mimp/Mtch2 mice exhibit high blood glucose levels. Our results also show that Mimp/Mtch2 is involved in lipid accumulation and uptake in cells and perhaps in human obesity. CONCLUSIONS: Mimp/Mtch2 alters lipid metabolism and may play a role in the onset of obesity and development of insulin resistance. PMID- 27359330 TI - Endophytic Fungi from Frankincense Tree Improves Host Growth and Produces Extracellular Enzymes and Indole Acetic Acid. AB - Boswellia sacra, an economically important frankincense-producing tree found in the desert woodlands of Oman, is least known for its endophytic fungal diversity and the potential of these fungi to produce extracellular enzymes and auxins. We isolated various fungal endophytes belonging to Eurotiales (11.8%), Chaetomiaceae (17.6%), Incertae sadis (29.5%), Aureobasidiaceae (17.6%), Nectriaceae (5.9%) and Sporomiaceae (17.6%) from the phylloplane (leaf) and caulosphere (stem) of the tree. Endophytes were identified using genomic DNA extraction, PCR amplification and sequencing the internal transcribed spacer regions, whereas a detailed phylogenetic analysis of the same gene fragment was made with homologous sequences. The endophytic colonization rate was significantly higher in the leaf (5.33%) than the stem (0.262%). The Shannon-Weiner diversity index was H' 0.8729, while Simpson index was higher in the leaf (0.583) than in the stem (0.416). Regarding the endophytic fungi's potential for extracellular enzyme production, fluorogenic 4-methylumbelliferone standards and substrates were used to determine the presence of cellulases, phosphatases and glucosidases in the pure culture. Among fungal strains, Penicillum citrinum BSL17 showed significantly higher amounts of glucosidases (62.15+/-1.8 MUM-1min-1mL) and cellulases (62.11+/-1.6 MUM-1min-1mL), whereas Preussia sp. BSL10 showed significantly higher secretion of glucosidases (69.4+/-0.79 MUM-1min-1mL) and phosphatases (3.46+/-0.31MUM-1min 1mL) compared to other strains. Aureobasidium sp. BSS6 and Preussia sp. BSL10 showed significantly higher potential for indole acetic acid production (tryptophan-dependent and independent pathways). Preussia sp. BSL10 was applied to the host B. sacra tree saplings, which exhibited significant improvements in plant growth parameters and accumulation of photosynthetic pigments. The current study concluded that endophytic microbial resources producing extracellular enzymes and auxin could establish a unique niche for ecological adaptation during symbiosis with the host Frankincense tree. PMID- 27359331 TI - Quasi-steady aerodynamic model of clap-and-fling flapping MAV and validation using free-flight data. AB - Flapping-wing aerodynamic models that are accurate, computationally efficient and physically meaningful, are challenging to obtain. Such models are essential to design flapping-wing micro air vehicles and to develop advanced controllers enhancing the autonomy of such vehicles. In this work, a phenomenological model is developed for the time-resolved aerodynamic forces on clap-and-fling ornithopters. The model is based on quasi-steady theory and accounts for inertial, circulatory, added mass and viscous forces. It extends existing quasi steady approaches by: including a fling circulation factor to account for unsteady wing-wing interaction, considering real platform-specific wing kinematics and different flight regimes. The model parameters are estimated from wind tunnel measurements conducted on a real test platform. Comparison to wind tunnel data shows that the model predicts the lift forces on the test platform accurately, and accounts for wing-wing interaction effectively. Additionally, validation tests with real free-flight data show that lift forces can be predicted with considerable accuracy in different flight regimes. The complete parameter-varying model represents a wide range of flight conditions, is computationally simple, physically meaningful and requires few measurements. It is therefore potentially useful for both control design and preliminary conceptual studies for developing new platforms. PMID- 27359332 TI - [Nle4, D-Phe7]-alpha-MSH Inhibits Toll-Like Receptor (TLR)2- and TLR4-Induced Microglial Activation and Promotes a M2-Like Phenotype. AB - alpha-melanocyte stimulating hormone (alpha-MSH) is an anti-inflammatory peptide, proved to be beneficial in many neuroinflammatory disorders acting through melanocortin receptor 4 (MC4R). We previously determined that rat microglial cells express MC4R and that NDP-MSH, an analog of alpha-MSH, induces PPAR-gamma expression and IL-10 release in these cells. Given the great importance of modulation of glial activation in neuroinflammatory disorders, we tested the ability of NDP-MSH to shape microglial phenotype and to modulate Toll-like receptor (TLR)-mediated inflammatory responses. Primary rat cultured microglia were stimulated with NDP-MSH followed by the TLR2 agonist Pam3CSK4 or the TLR4 agonist LPS. NDP-MSH alone induced expression of the M2a/M2c marker Ag1 and reduced expression of the M2b marker Il-4ralpha and of the LPS receptor Tlr4. Nuclear translocation of NF-kappaB subunits p65 and c-Rel was induced by LPS and these effects were partially prevented by NDP-MSH. NDP-MSH reduced LPS- and Pam3CSK4-induced TNF-alpha release but did not affect TLR-induced IL-10 release. Also, NDP-MSH inhibited TLR2-induced HMGB1 translocation from nucleus to cytoplasm and TLR2-induced phagocytic activity. Our data show that NDP-MSH inhibits TLR2- and TLR4-mediated proinflammatory mechanisms and promotes microglial M2-like polarization, supporting melanocortins as useful tools for shaping microglial activation towards an alternative immunomodulatory phenotype. PMID- 27359333 TI - Standards of care for obsessive-compulsive disorder centres. AB - In recent years, many assessment and care units for obsessive-compulsive disorder (OCD) have been set up in order to detect, diagnose and to properly manage this complex disorder, but there is no consensus regarding the key functions that these units should perform. The International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) together with the Obsessive Compulsive and Related Disorders Network (OCRN) of the European College of Neuropsychopharmacology (ECNP) and the Anxiety and Obsessive Compulsive Disorders Section of the World Psychiaric Association (WPA) has developed a standards of care programme for OCD centres. The goals of this collaborative initiative are promoting basic standards, improving the quality of clinical care and enhance the validity and reliability of research results provided by different facilities and countries. PMID- 27359334 TI - Evolutionary and Topological Properties of Genes and Community Structures in Human Gene Regulatory Networks. AB - The diverse, specialized genes present in today's lifeforms evolved from a common core of ancient, elementary genes. However, these genes did not evolve individually: gene expression is controlled by a complex network of interactions, and alterations in one gene may drive reciprocal changes in its proteins' binding partners. Like many complex networks, these gene regulatory networks (GRNs) are composed of communities, or clusters of genes with relatively high connectivity. A deep understanding of the relationship between the evolutionary history of single genes and the topological properties of the underlying GRN is integral to evolutionary genetics. Here, we show that the topological properties of an acute myeloid leukemia GRN and a general human GRN are strongly coupled with its genes' evolutionary properties. Slowly evolving ("cold"), old genes tend to interact with each other, as do rapidly evolving ("hot"), young genes. This naturally causes genes to segregate into community structures with relatively homogeneous evolutionary histories. We argue that gene duplication placed old, cold genes and communities at the center of the networks, and young, hot genes and communities at the periphery. We demonstrate this with single-node centrality measures and two new measures of efficiency, the set efficiency and the interset efficiency. We conclude that these methods for studying the relationships between a GRN's community structures and its genes' evolutionary properties provide new perspectives for understanding evolutionary genetics. PMID- 27359335 TI - Outcome Prediction of Consciousness Disorders in the Acute Stage Based on a Complementary Motor Behavioural Tool. AB - INTRODUCTION: Attaining an accurate diagnosis in the acute phase for severely brain-damaged patients presenting Disorders of Consciousness (DOC) is crucial for prognostic validity; such a diagnosis determines further medical management, in terms of therapeutic choices and end-of-life decisions. However, DOC evaluation based on validated scales, such as the Revised Coma Recovery Scale (CRS-R), can lead to an underestimation of consciousness and to frequent misdiagnoses particularly in cases of cognitive motor dissociation due to other aetiologies. The purpose of this study is to determine the clinical signs that lead to a more accurate consciousness assessment allowing more reliable outcome prediction. METHODS: From the Unit of Acute Neurorehabilitation (University Hospital, Lausanne, Switzerland) between 2011 and 2014, we enrolled 33 DOC patients with a DOC diagnosis according to the CRS-R that had been established within 28 days of brain damage. The first CRS-R assessment established the initial diagnosis of Unresponsive Wakefulness Syndrome (UWS) in 20 patients and a Minimally Consciousness State (MCS) in the remaining13 patients. We clinically evaluated the patients over time using the CRS-R scale and concurrently from the beginning with complementary clinical items of a new observational Motor Behaviour Tool (MBT). Primary endpoint was outcome at unit discharge distinguishing two main classes of patients (DOC patients having emerged from DOC and those remaining in DOC) and 6 subclasses detailing the outcome of UWS and MCS patients, respectively. Based on CRS-R and MBT scores assessed separately and jointly, statistical testing was performed in the acute phase using a non-parametric Mann Whitney U test; longitudinal CRS-R data were modelled with a Generalized Linear Model. RESULTS: Fifty-five per cent of the UWS patients and 77% of the MCS patients had emerged from DOC. First, statistical prediction of the first CRS-R scores did not permit outcome differentiation between classes; longitudinal regression modelling of the CRS-R data identified distinct outcome evolution, but not earlier than 19 days. Second, the MBT yielded a significant outcome predictability in the acute phase (p<0.02, sensitivity>0.81). Third, a statistical comparison of the CRS-R subscales weighted by MBT became significantly predictive for DOC outcome (p<0.02). DISCUSSION: The association of MBT and CRS-R scoring improves significantly the evaluation of consciousness and the predictability of outcome in the acute phase. Subtle motor behaviour assessment provides accurate insight into the amount and the content of consciousness even in the case of cognitive motor dissociation. PMID- 27359336 TI - Rationalisation and Validation of an Acrylamide-Free Procedure in Three Dimensional Histological Imaging. AB - Three-dimensional visualization of intact tissues is now being achieved by turning tissues transparent. CLARITY is a unique tissue clearing technique, which features the use of detergents to remove lipids from fixed tissues to achieve optical transparency. To preserve tissue integrity, an acrylamide-based hydrogel has been proposed to embed the tissue. In this study, we examined the rationale behind the use of acrylamide in CLARITY, and presented evidence to suggest that the omission of acrylamide-hydrogel embedding in CLARITY does not alter the preservation of tissue morphology and molecular information in fixed tissues. We therefore propose a novel and simplified workflow for formaldehyde-fixed tissue clearing, which will facilitate the laboratory implementation of this technique. Furthermore, we have investigated the basic tissue clearing process in detail and have highlighted some areas for targeted improvement of technologies essential for the emerging subject of three-dimensional histology. PMID- 27359337 TI - Indigenous Elder Insights About Conventional Care Services in Alaska: Culturally Charged Spaces. AB - : Indigenous peoples around the world endure health and social disparities. In the United States, such disparities are typically ameliorated through conventional care services and organizations. PURPOSE: To examine points of tension that characterize culturally pluralistic care services in the United States, specifically Alaska, within context of Indigenous colonial histories. DESIGN AND METHODS: The research design is ethnographic and multisited, comprising 12 months of fieldwork across urban, rural and remote village sites in Alaska. A conceptual lens that accounts for culturally diverse social spaces where relations of power are at stake frames research presented here. This work incorporates relational and participatory action research principles with Alaska Native Elders. Ethnographic evidence was collected through multiple methods, including field notes, documents, and interviews, with ethnographic analysis involving atlas.ti. FINDINGS: Alaska Native Elders describe salient points of tension characterizing Alaska's conventional care services through the following insights: generational curses--a pain, prejudice on both sides-wounded, and value systems clash-fighting. CONCLUSION: This article concludes with discussion about collective anxieties and implications for care services. PMID- 27359338 TI - Transcranial Direct Current Stimulation to Enhance Dual-Task Gait Training in Parkinson's Disease: A Pilot RCT. AB - OBJECTIVE: To investigate the feasibility and safety of a combined anodal transcranial direct current stimulation (tDCS) and dual task gait training intervention in people with Parkinson's Disease (PD) and to provide data to support a sample size calculation for a fully powered trial should trends of effectiveness be present. DESIGN: A pilot, randomized, double-blind, sham controlled parallel group trial with 12 week follow-up. SETTING: A university physiotherapy department. INTERVENTIONS: Sixteen participants diagnosed with PD received nine dual task gait training sessions over 3 weeks. Participants were randomized to receive either active or sham tDCS applied for the first 20 minutes of each session. MAIN MEASURES: The primary outcome was gait speed while undertaking concurrent cognitive tasks (word lists, counting, conversation). Secondary measures included step length, cadence, Timed Up and Go, bradykinesia and motor speed. RESULTS: Gait speed, step length and cadence improved in both groups, under all dual task conditions. This effect was maintained at follow-up. There was no difference between the active and sham tDCS groups. Time taken to perform the TUGwords also improved, with no difference between groups. The active tDCS group did however increase their correct cognitive response rate during the TUGwords and TUGcount. Bradykinesia improved after training in both groups. CONCLUSION: Three weeks of dual task gait training resulted in improved gait under dual task conditions, and bradykinesia, immediately following training and at 12 weeks follow-up. The only parameter enhanced by tDCS was the number of correct responses while performing the dual task TUG. tDCS applied to M1 may not be an effective adjunct to dual task gait training in PD. TRIAL REGISTRATION: Australia-New Zealand Clinical Trials Registry ACTRN12613001093774. PMID- 27359339 TI - Urine Monocyte Chemoattractant Protein-1 Is an Independent Predictive Factor of Hospital Readmission and Survival in Cirrhosis. AB - MCP-1 (monocyte chemoattractant protein-1) is a proinflammatory cytokine involved in chemotaxis of monocytes. In several diseases, such as acute coronary syndromes and heart failure, elevated MCP-1 levels have been associated with poor outcomes. Little is known about MCP-1 in cirrhosis. AIM: To investigate the relationship between MCP-1 and outcome in decompensated cirrhosis. METHODS: Prospective study of 218 patients discharged from hospital after an admission for complications of cirrhosis. Urine and plasma levels of MCP-1 and other urine proinflammatroy biomarkers: osteopontin(OPN), trefoil-factor3 and liver-fatty-acid-binding protein were measured at admission. Urine non-inflammatory mediators cystatin-C, beta2microglobulin and albumin were measured as control biomarkers. The relationship between these biomarkers and the 3-month hospital readmission, complications of cirrhosis, and mortality were assessed. RESULTS: 69 patients(32%) had at least one readmission during the 3-month period of follow-up and 30 patients died(14%). Urine MCP-1 and OPN levels, were associated with 3 month probability of readmission (0.85 (0.27-2.1) and 2003 (705-4586) ug/g creat vs 0.47 (0.2-1.1) and 1188 (512-2958) ug/g creat, in patients with and without readmission, respectively; p<0.05; median (IQR)). Furthermore, urine levels of MCP-1 were significantly associated with mortality (1.01 (1-3.6) vs 0.5 (0.2-1.1) MUg/g creat, in dead and alive patients at 3 months; p<0.05). Patients with higher levels of urine MCP-1 (above percentile 75th) had higher probability of development of hepatic encephalopathy, bacterial infections or AKI. Urine MCP-1 was an independent predictive factor of hospital readmission and combined end point of readmission or dead at 3 months. Plasma levels of MCP-1 did not correlated with outcomes. CONCLUSION: Urine, but not plasma, MCP-1 levels are associated with hospital readmission, development of complications of cirrhosis, and mortality. These results suggest that in cirrhosis there is an inflammatory response that is associated with poor outcomes. PMID- 27359340 TI - Intact Protein Quantitation Using Pseudoisobaric Dimethyl Labeling. AB - Protein structural and functional studies rely on complete qualitative and quantitative information on protein species (proteoforms); thus, it is important to quantify differentially expressed proteins at their molecular level. Here we report our development of universal pseudoisobaric dimethyl labeling (pIDL) of amino groups at both the N-terminal and lysine residues for relative quantitation of intact proteins. Initial proof-of-principle study was conducted on standard protein myoglobin and hepatocellular proteomes (HepG2 vs LO2). The amino groups from both the N-terminal and lysine were dimethylated with HXHO (X = (13)C or C) and NaBY3CN (Y = H or D). At the standard protein level, labeling efficiency, effect of product ion size, and mass resolution on quantitation accuracy were explored; and a good linear quantitation dynamic range up to 50-fold was obtained. For the hepatocellular proteome samples, 33 proteins were quantified with RSD <= 10% from one-dimensional reversed phase liquid chromatography-tandem mass spectrometry (RPLC-MS/MS) analysis of the 1:1 mixed samples. The method in this study can be extended to quantitation of other intact proteome systems. The universal "one-pot" dimethyl labeling of all the amino groups in a protein without the need of preblocking of those on the lysine residues is made possible by protein identification and quantitation analysis using ProteinGoggle 2.0 with customized databases of both precursor and product ions containing heavy isotopes. PMID- 27359341 TI - Measured Wavelength-Dependent Absorption Enhancement of Internally Mixed Black Carbon with Absorbing and Nonabsorbing Materials. AB - Optical absorption spectra of laboratory generated aerosols consisting of black carbon (BC) internally mixed with nonabsorbing materials (ammonium sulfate, AS, and sodium chloride, NaCl) and BC with a weakly absorbing brown carbon surrogate derived from humic acid (HA) were measured across the visible to near-IR (550 to 840 nm). Spectra were measured in situ using a photoacoustic spectrometer and step-scanning a supercontinuum laser source with a tunable wavelength and bandwidth filter. BC had a mass-specific absorption cross section (MAC) of 7.89 +/- 0.25 m(2) g(-1) at lambda = 550 nm and an absorption Angstrom exponent (AAE) of 1.03 +/- 0.09 (2sigma). For internally mixed BC, the ratio of BC mass to the total mass of the mixture was chosen as 0.13 to mimic particles observed in the terrestrial atmosphere. The manner in which BC mixed with each material was determined from transmission electron microscopy (TEM). AS/BC and HA/BC particles were fully internally mixed, and the BC was both internally and externally mixed for NaCl/BC particles. The AS/BC, NaCl/BC, and HA/BC particles had AAEs of 1.43 +/- 0.05, 1.34 +/- 0.06, and 1.91 +/- 0.05, respectively. The observed absorption enhancement of mixed BC relative to the pure BC was wavelength dependent for AS/BC and decreased from 1.5 at lambda = 550 nm with increasing wavelength while the NaCl/BC enhancement was essentially wavelength independent. For HA/BC, the enhancement ranged from 2 to 3 and was strongly wavelength dependent. Removal of the HA absorption contribution to enhancement revealed that the enhancement was ~1.5 and independent of wavelength. PMID- 27359342 TI - Genetic Diversity of Oilseed Rape Fields and Feral Populations in the Context of Coexistence with GM Crops. AB - Despite growing concern about transgenes escaping from fields, few studies have analysed the genetic diversity of crops in an agroecosystem over several years. Accurate information about the dynamics and relationship of the genetic diversity of crops in an agroecosystem is essential for risk assessment and policies concerning the containment of genetically modified crops and their coexistence with crops grown by conventional practices. Here, we analysed the genetic diversity of oilseed rape plants from fields and feral populations over 4 years in an agricultural landscape of 41 km2. We used exact compatibility and maximum likelihood assignment methods to assign these plants to cultivars. Even pure lines and hybrid cultivar seed lots contained several genotypes. The cultivar diversity in fields reflected the conventional view of agroecosystems quite well: that is, there was a succession of cultivars, some grown for longer than others because of their good performance, some used for one year and then abandoned, and others gradually adopted. Three types of field emerged: fields sown with a single cultivar, fields sown with two cultivars, and unassigned fields (too many cultivars or unassigned plants to reliably assign the field). Field plant diversity was higher than expected, indicating the persistence of cultivars that were grown for only one year. The cultivar composition of feral populations was similar to that of field plants, with an increasing number of cultivars each year. By using genetic tools, we found a link between the cultivars of field plants in a particular year and the cultivars of feral population plants in the following year. Feral populations on road verges were more diverse than those on path verges. All of these findings are discussed in terms of their consequences in the context of coexistence with genetically modified crops. PMID- 27359344 TI - Ethenolysis: A Green Catalytic Tool to Cleave Carbon-Carbon Double Bonds. AB - Remarkable innovations have been made in the field of olefin metathesis due to the design and preparation of new catalysts. Ethenolysis, which is cross metathesis with ethylene, represents one catalytic transformation that has been used with the purpose of cleaving internal carbon-carbon double bonds. The objectives were either the ring opening of cyclic olefins to produce dienes or the shortening of unsaturated hydrocarbon chains to degrade polymers or generate valuable shorter terminal olefins in a controlled manner. This Review summarizes several aspects of this reaction: the catalysts, their degradation in the presence of ethylene, some parameters driving their productivity, the side reactions, and the applications of ethenolysis in organic synthesis and in potential industrial applications. PMID- 27359345 TI - Hope as determinant for psychiatric morbidity in family caregivers of advanced cancer patients. AB - OBJECTIVE: Home care of advanced cancer patients often has adverse effects on physical and mental health of family caregivers. Little is known about the long term effects of continuous caregiving on mental health as compared with the effects of bereavement. The objectives of this study were to describe the course of psychiatric morbidity in family caregivers over time, to identify the impact of the patients' death on caregivers, and to explore possible predictor variables for psychiatric morbidity. METHODS: This multi-institutional, prospective study included 80 family caregivers of 80 advanced cancer patients for baseline and 9 months follow-up assessment. Possible psychiatric disorders (ie, depression, anxiety, posttraumatic stress disorder, and alcohol abuse/dependence) as well as potentially predictive factors (ie, sociodemographic factors, burden, hope, and coping mechanisms) were assessed. RESULTS: Follow-up assessment was conducted on average 9.2 months (+/-2.9) after baseline assessment. Prevalence rates of anxiety and posttraumatic stress disorder decreased significantly over time, whereas depression and alcoholism remained stable. Bereavement was experienced by 53% of caregivers in the follow-up period. The patients' death had no influence on psychiatric morbidity at follow-up. Predictors for the development of a psychiatric disorder varied according to condition, with hope and emotion oriented coping identified as important influences, especially for anxiety and depression. CONCLUSION: Family caregivers with certain psychiatric disorders might need targeted psychosocial support to ensure their mental well-being and prevent long-term disability. Supporting hope and functional coping strategies early after the patient's diagnosis might limit development and extent of psychiatric morbidity. PMID- 27359346 TI - A Cross-Cultural Analysis of Personality Structure Through the Lens of the HEXACO Model. AB - Across 5 different samples, totaling more than 1,600 participants from India, Indonesia, Oman, Romania, and Thailand, the authors address the question of cross cultural replicability of a personality structure, while exploring the utility of exploratory structural equation modeling (ESEM) as a data analysis technique in cross-cultural personality research. Personality was measured with an alternative, non-Five-Factor Model (FFM) personality framework, provided by the HEXACO-PI (Lee & Ashton, 2004 ). The results show that the HEXACO framework was replicated in some of the investigated cultures. The ESEM data analysis technique proved to be especially useful in investigating the between-group measurement equivalence of broad personality measures across different cultures. PMID- 27359347 TI - Accelerated Broadband Spectra Using Transition Dipole Decomposition and Pade Approximants. AB - We present a method for accelerating the computation of UV-visible and X-ray absorption spectra in large molecular systems using real-time time-dependent density functional theory (TDDFT). This approach is based on deconvolution of the dipole into molecular orbital dipole pairs developed by Repisky, et al. [Repisky et al., J. Chem. Theory Comput. 2015, 11, 980-911] followed by Pade approximants to their Fourier transforms. By combining these two techniques, the required simulation time is reduced by a factor of 5 or more, and moreover, the transition dipoles yield the molecular orbital contributions to each transition, akin to the coefficients in linear-response TDDFT. We validate this method on valence and core-level spectra of gas-phase water and nickel porphyrin, where the results are essentially equivalent to conventional linear response. This approach makes real time TDDFT competitive against linear response for large molecular and material systems with a high density of states. PMID- 27359343 TI - Evolutionary perspectives of telomerase RNA structure and function. AB - Telomerase is the eukaryotic solution to the 'end-replication problem' of linear chromosomes by synthesising the highly repetitive DNA constituent of telomeres, the nucleoprotein cap that protects chromosome termini. Functioning as a ribonucleoprotein (RNP) enzyme, telomerase is minimally composed of the highly conserved catalytic telomerase reverse transcriptase (TERT) and essential telomerase RNA (TR) component. Beyond merely providing the template for telomeric DNA synthesis, TR is an innate telomerase component and directly facilitates enzymatic function. TR accomplishes this by having evolved structural elements for stable assembly with the TERT protein and the regulation of the telomerase catalytic cycle. Despite its prominence and prevalence, TR has profoundly diverged in length, sequence, and biogenesis pathway among distinct evolutionary lineages. This diversity has generated numerous structural and mechanistic solutions for ensuring proper RNP formation and high fidelity telomeric DNA synthesis. Telomerase provides unique insights into RNA and protein coevolution within RNP enzymes. PMID- 27359348 TI - Thrombolysis by chemically modified coagulation factor Xa. AB - Essentials Factor Xa (FXa) acquires cleavage-mediated tissue plasminogen activator (tPA) cofactor activity. Recombinant (r) tPA is the predominant thrombolytic drug, but it may cause systemic side effects. Chemically modified, non-enzymatic FXa was produced (Xai-K), which rapidly lysed thrombi in mice. Unlike rtPA, Xai-K had no systemic fibrinolysis activation markers, indicating improved safety. SUMMARY: Background Enzymatic thrombolysis carries the risk of hemorrhage and re-occlusion must be evaded by co-administration with an anticoagulant. Toward further improving these shortcomings, we report a novel dual-functioning molecule, Xai-K, which is both a non-enzymatic thrombolytic agent and an anticoagulant. Xai-K is based on clotting factor Xa, whose sequential plasmin-mediated fragments, FXabeta and Xa33/13, accelerate the principal thrombolytic agent, tissue plasminogen activator (tPA), but only when localized to anionic phospholipid. Methods The effect of Xai-K on fibrinolysis was measured in vitro by turbidity, thromboelastography and chromogenic assays, and measured in a murine model of occlusive carotid thrombosis by Doppler ultrasound. The anticoagulant properties of Xai-K were evaluated by normal plasma clotting assays, and in murine liver laceration and tail amputation hemostatic models. Results Xa33/13, which participates in fibrinolysis of purified fibrin, was rapidly inhibited in plasma. Cleavage was blocked at FXabeta by modifying residues at the active site. The resultant Xai-K (1 nm) enhanced plasma clot dissolution by ~7-fold in vitro and was dependent on tPA. Xai-K alone (2.0 MUg g( 1) body weight) achieved therapeutic patency in mice. The minimum primary dose of the tPA variant, Tenecteplase (TNK; 17 MUg g(-1) ), could be reduced by > 30-fold to restore blood flow with adjunctive Xai-K (0.5 MUg g(-1) ). TNK-induced systemic markers of fibrinolysis were not detected with Xai-K (2.0 MUg g(-1) ). Xai-K had anticoagulant activity that was somewhat attenuated compared with a previously reported analogue. Conclusion These results suggest that Xai-K may ameliorate the safety profile of therapeutic thrombolysis, either as a primary or tPA/TNK-adjunctive agent. PMID- 27359350 TI - Blood Lead Levels Among Children Aged <6 Years - Flint, Michigan, 2013-2016. AB - During April 25, 2014-October 15, 2015, approximately 99,000 residents of Flint, Michigan, were affected by changes in drinking water quality after their water source was switched from the Detroit Water Authority (DWA), sourced from Lake Huron, to the Flint Water System (FWS), sourced from the Flint River.* Because corrosion control was not used at the FWS water treatment plant, the levels of lead in Flint tap water increased over time. Adverse health effects are associated with lead exposure (1). On January 2, 2015, a water advisory was issued because of detection of high levels of trihalomethanes, byproducts of disinfectants.(?)(,)(S) Studies conducted by local and national investigators detected an increase in the prevalence of blood lead levels (BLLs) >=5 ug/dL (the CDC reference level) among children aged <5 years living in Flint (2) and an increase in water lead levels after the water source switch (3). On October 16, 2015, the Flint water source was switched back to DWA, and residents were instructed to use filtered tap water for cooking and drinking. During that time, pregnant and breastfeeding women and children aged <6 years were advised to consume bottled water.( ) To assess the impact on BLLs of consuming contaminated drinking water, CDC examined the distribution of BLLs >=5 ug/dL among children aged <6 years before, during, and after the switch in water source. This analysis enabled determination of whether the odds of having BLLs >=5 ug/dL before the switch differed from the odds during the switch to FWS (before and after the January 2, 2015, water advisory was issued), and after the switch back to DWA. Overall, among 9,422 blood lead tests in children aged <6 years, 284 (3.0%) BLLs were >=5 ug/dL during April 25, 2013-March 16, 2016. The adjusted probability of having BLLs >=5 ug/dL was 46% higher during the period after the switch from DWA to FWS (and before the January 2, 2015, water advisory) than during the period before the water switch to FWS. Although unrelated to lead in the water, the water advisory likely reduced tap water consumption and increased consumption of bottled water. Characterizing exposure to lead contaminated drinking water among children aged <6 years living in Flint can help guide appropriate interventions. PMID- 27359349 TI - Claudin-2-mediated cation and water transport share a common pore. AB - AIM: Claudin-2 is a tight junction protein typically located in 'leaky' epithelia exhibiting large paracellular permeabilities like small intestine and proximal kidney tubule. Former studies revealed that claudin-2 forms paracellular channels for small cations like sodium and potassium and also paracellular channels for water. This study analyses whether the diffusive transport of sodium and water occurs through a common pore of the claudin-2 channel. METHODS: Wild-type claudin 2 and different claudin-2 mutants were expressed in MDCK I kidney tubule cells using an inducible system. Ion and water permeability and the effect of blocking reagents on both were investigated on different clones of the mutants. RESULTS: Neutralization of a negatively charged cation interaction site in the pore with the mutation, D65N, decreased both sodium permeability and water permeability. Claudin-2 mutants (I66C and S68C) with substitution of the pore-lining amino acids with cysteine were used to test the effect of steric blocking of the claudin-2 pore by thiol-reactive reagents. Addition of thiol-reactive reagents to these mutants simultaneously decreased conductance and water permeability. Remarkably, all experimental perturbations caused parallel changes in ion conductance and water permeability, disproving different or independent passage pathways. CONCLUSION: Our results indicate that claudin-2-mediated cation and water transport are frictionally coupled and share a common pore. This pore is lined and determined in permeability by amino acid residues of the first extracellular loop of claudin-2. PMID- 27359352 TI - Atomic Layer Deposited Corrosion Protection: A Path to Stable and Efficient Photoelectrochemical Cells. AB - A fundamental challenge in developing photoelectrochemical cells for the renewable production of solar chemicals and fuels is the simultaneous requirement of efficient light absorption and robust stability under corrosive conditions. Schemes for corrosion protection of semiconductor photoelectrodes such as silicon using deposited layers were proposed and attempted for several decades, but increased operational lifetimes were either insufficient or the resulting penalties for device efficiency were prohibitive. In recent years, advances in atomic layer deposition (ALD) of thin coatings have made novel materials engineering possible, leading to substantial and simultaneous improvements in stability and efficiency of photoelectrochemical cells. The self-limiting, layer by-layer growth of ALD makes thin films with low pinhole densities possible and may also provide a path to defect control that can generalize this protection technology to a large set of materials necessary to fully realize photoelectrochemical cell technology for artificial photosynthesis. PMID- 27359351 TI - Farnesoid X receptor activation increases reverse cholesterol transport by modulating bile acid composition and cholesterol absorption in mice. AB - Activation of farnesoid X receptor (FXR) markedly attenuates development of atherosclerosis in animal models. However, the underlying mechanism is not well elucidated. Here, we show that the FXR agonist, obeticholic acid (OCA), increases fecal cholesterol excretion and macrophage reverse cholesterol transport (RCT) dependent on activation of hepatic FXR. OCA does not increase biliary cholesterol secretion, but inhibits intestinal cholesterol absorption. OCA markedly inhibits hepatic cholesterol 7alpha-hydroxylase (Cyp7a1) and sterol 12alpha-hydroxylase (Cyp8b1) partly through inducing small heterodimer partner, leading to reduced bile acid pool size and altered bile acid composition, with the alpha/beta muricholic acid proportion in bile increased by 2.6-fold and taurocholic acid (TCA) level reduced by 71%. Overexpression of Cyp8b1 or concurrent overexpression of Cyp7a1 and Cyp8b1 normalizes TCA level, bile acid composition, and intestinal cholesterol absorption. CONCLUSION: Activation of FXR inhibits intestinal cholesterol absorption by modulation of bile acid pool size and composition, thus leading to increased RCT. Targeting hepatic FXR and/or bile acids may be useful for boosting RCT and preventing the development of atherosclerosis. (Hepatology 2016;64:1072-1085). PMID- 27359353 TI - To the Editor. PMID- 27359354 TI - To the Editor. PMID- 27359355 TI - To the Editor. PMID- 27359357 TI - Response to the Letter to the Editor. PMID- 27359356 TI - Association Between Cartilage Intermediate Layer Protein and Degeneration of Intervertebral Disc: A Meta-analysis. AB - STUDY DESIGN: Meta-analysis to collect all eligible studies for investigating whether cartilage intermediate layer protein (CILP) gene rs2073711 polymorphism is associated with susceptibility to intervertebral disc degeneration (IVD). OBJECTIVE: To investigate the association between CILP gene rs2073711 and IVD. SUMMARY OF BACKGROUND DATA: CILP is one of the limited genes that is being suggested to be associated with IVD. However, previous association study results of CILP and IVD are conflicted. METHODS: The PubMed, ISI Web of Science, Science Direct Online, and China National Knowledge Infrastructure database were searched for relevant articles till November 1, 2015. The odds ratio (OR) and related 95% confidence interval (CI) were drawn out and merged to assess the strength of association by STATA version 12.0. RESULTS: A total of 1551 IVD cases and 1793 controls from the 5 studies were used in this study, comprising four Asian populations and two European populations. Meta-analysis found that the CILP 2073711 polymorphism was significantly associated with IVD risk. The estimated OR of risk allele T of rs2073711 was 1.36. (95% CI = 1.18-1.55, P < 0.001). No significant heterogeneity and publication bias were observed in this study. CONCLUSION: Our results confirm the positive association between CILP and IVD, providing novel clues for clarifying the role of CILP in the development of IVD. LEVEL OF EVIDENCE: 2. PMID- 27359358 TI - Effect of Surgeon Volume on Complications, Length of Stay, and Costs Following Anterior Cervical Fusion. AB - STUDY DESIGN: Retrospective cohort. OBJECTIVE: To identify the association between surgeon volume and inpatient complications, length of stay, and costs associated with ACF. SUMMARY OF BACKGROUND DATA: Increased surgeon volume may be associated with improved outcomes after surgical procedures. However, there is a lack of information on the effect of surgeon volume on short-term outcomes after anterior cervical fusion (ACF). METHODS: A retrospective cohort study of ACF patients was performed using the Nationwide Inpatient Sample (NIS) from 2003 to 2009. Surgeon volume was divided into three categories, volume <25th percentile, 25th to 74th percentile, and >=75th percentile of surgeon volume. Multivariate regression was used to compare the rates of adverse events, hospital length of stay, and total hospital costs between surgeon volume categories. RESULTS: A total of 419,212 ACF patients were identified. The 25th percentile for volume was 5 cases per year, and the 75th percentile for volume was 67 cases per year. Volume <25th percentile was associated with increased rates of any adverse event (odd ratio, OR 3.8, P < 0.001), and multiple individual complications including death (OR 2.5, P=0.014), myocardial infarction (OR4.4, P < 0.001), sepsis (OR 4.1, P < 0.001), and surgical site infection (OR 4.0, P < 0.001). Notably, volume >=75th percentile was associated with decreased rates of any adverse event (OR 0.7, P < 0.001) and death (OR 0.6, P = 0.028). On multivariate analysis, length of stay was significantly increased by 2.3 days (P < 0.001) for surgeons <25th percentile of volume and was decreased by 0.3 days for surgeons with volume >=75th percentile. Hospital costs were $4569 more for surgeons with <25th percentile of volume and $1213 less for surgeons with >=75th percentile volume. CONCLUSION: In this nationally representative sample, surgeons with volume <25th percentile had significantly increased complications, length of stay, and costs. Conversely, surgeons with >=75th percentile volume experienced decreased complications, length of stay, and costs. LEVEL OF EVIDENCE: 4. PMID- 27359360 TI - Complications and Mortality Following 1 to 2 Level Lumbar Fusion Surgery in Patients Above 80 Years of Age. AB - STUDY DESIGN: Retrospective database review. OBJECTIVE: To determine the 90-day complication rate and 90-day and 1-year mortality in patients 80 years of age and older who were treated with posterolateral lumbar spinal fusion surgery and to compare these rates against those of elderly patients ages 65 to 79. SUMMARY OF BACKGROUND DATA: Patients over 80 years of age specifically represent a substantial proportion of the US population, with over 11 million such individuals in 2010. Few studies have comprehensively assessed the morbidity associated with spinal fusion surgery in patients older than 80 years. METHODS: The PearlDiver database (2005-2012) was utilized to determine morbidity and mortality rates after posterolateral lumbar or lumbosacral spinal fusion surgery of 2-3 vertebrae. Patients 65 to 79 (72,547) and >=80-year old (12,187) were selected. Charlson comorbidity index scores were analyzed and compared, as were various comorbid conditions 90-day complication rates and mortality at 90-days and 1 year compared between cohorts. RESULTS: The >=80 year cohort had a higher average Charlson Comorbidity Index score than the 65 to 79 year cohort (7.99 vs. 6.54, P <0.0001). The proportion of patients experiencing at least one major complication was relatively increased by 45.6% in patients >=80 year (13.87 vs. 9.52%; OR 1.53 95% CI 1.44 - 1.62 P <0.0001). Ninety-day (0.30 vs. 0.09%; OR: 3.50, 95% confidence interval: 2.33-5.26, P <0.0001) and 1-year (0.48 vs. 0.18%; OR: 2.58, 95% confidence interval: 1.90-3.52, P <0.0001) mortality were significantly higher in the >=80 year cohort compared with the 65 to 79-year-old control group. CONCLUSION: Patients 80 years of age or older have significantly greater rates of major medical complication and mortality following 1 to 2 level lumbar spinal posterolateral fusion surgery compared with patients 65 to 79 years of age. LEVEL OF EVIDENCE: 3. PMID- 27359361 TI - Simvastatin Treatment Upregulates Anti-Fibrotic Bone Morphogenetic Protein-7 Expression at Rat Cardiac Allograft Rejection. AB - BACKGROUND: Bone morphogenetic protein (BMP)-7 mediates ischemic tolerance and anti-fibrotic effects in various organs such as kidney and heart. Recently, reno- and podocyte-protective effects of a potent HMG-CoA reductase inhibitor, pitavastatin, were accompanied by BMP-7 upregulation. METHODS: Here, we investigated the effect of simvastatin treatment on BMP-7 expression in major MHC mismatched rat cardiac allografts subjected to ischemia-reperfusion injury and adaptive immune activation at 10 days. RESULTS: We localized Smad2 activity and Reca-1+ fibroblast specific protein-1+ immunoreactivity, suggesting endothelial to-mesenchymal transition, at fibrotic borderline of cardiac allografts at 10 days. Simvastatin donor and recipient combination treatment significantly upregulated cardiac allograft BMP-7 expression when compared to nontreated controls at 10 days. CONCLUSION: The beneficial effect of statin treatment on cardiac allograft may in part be mediated through the upregulation of BMP-7. PMID- 27359362 TI - Mechanistic Observations on the Role of the Stannous Ion in Caries Lesion De- and Remineralization. AB - Two mechanistic, laboratory, factorial design studies were conducted to investigate the effect of the stannous ion (Sn2+) in the absence or presence of fluoride on caries lesion de- and remineralization. Study I was concerned with determining changes in mineral distribution of subsurface lesions, whereas study II investigated changes in surface hardness of surface-softened lesions as a function of pH. Study I showed that Sn2+ modulates the effects of fluoride by preventing lamination. Study II revealed that the effect of Sn2+ on rehardening is pH dependent. Neither study demonstrated synergy between Sn2+ and fluoride, yet interactions were observed. Sn2+ does interfere with remineralization to some extent although it provided acid resistance. The role of Sn2+ in the caries process is complex. PMID- 27359363 TI - An Infection-Responsive Approach To Reduce Bacterial Adhesion in Urinary Biomaterials. AB - Infection is an inevitable consequence of chronic urinary catheterization with associated problems of recurrent catheter encrustation and blockage experienced by approximately 50% of all long-term catheterized patients. In this work, we have exploited, for the first time, the reported pathogen-induced elevation of urine pH as a trigger for "intelligent" antimicrobial release from novel hydrogel drug delivery systems of 2-hydroxyethyl methacrylate and vinyl-functionalized nalidixic acid derivatives, developed as candidate infection-resistant urinary catheter coatings. Demonstrating up to 20-fold faster rates of drug release at pH 10, representing infected urine pH, than at pH 7 and achieving reductions of up to 96.5% in in vitro bacterial adherence, our paradigm of pH-responsive drug delivery, which requires no external manipulation, therefore represents a promising development toward the prevention of catheter-associated urinary tract infections in vivo. PMID- 27359364 TI - Prevalence, awareness, treatment, and control of hypertension among China's Sichuan Tibetan population: A cross-sectional study. AB - BACKGROUND: Our aim is to investigate the prevalence, awareness, treatment, and control status of hypertension and explore the associated factors among Sichuan Tibetan population. METHODS: A cross-sectional investigation was conducted in the Sichuan Tibetan region from to September 2013 to March to 2014. Three thousand two hundred and forty persons were included in the study through a multi-stage stratified clustering sampling. Participants received questionnaires and physical examination. Blood pressure (BP) was recorded three times after 5 min of rest with the mean taken as the final BP. Hypertension was defined according the 2010 Chinese guidelines for the management of hypertension. RESULTS: Prevalence of hypertension was 45.7%. The proportion of different stages (1-3) of hypertension was 31.7%, 9.2%, and 7.6% for males and 26.3%, 9.5%, and 6.0% for females. The rate of awareness, treatment, and control of hypertension were 4.9%, 21.3%, and 3.0% for males and 7.5%, 24.5%, and 3.1% for females. Multiple-factor analysis found that age, overweight or obesity (odds ratio(OR)=1.16), drinking alcohol (OR = 1.29, 95% confidence interval (CI):1.07-1.54), increased waist circumference (OR = 1.81, 95%CI: 1.39-2.36), family history of hypertension (OR = 1.51, 95%CI; 1.28-1.78), higher salt intakes (OR = 1.62, 95%CI: 1.24-2.11), long duration of sleep (OR = 1.05, 95%CI: 1.01-1.09), rural area (OR = 1.99, 95%CI: 1.64-2.41), and drinking coffee at times (OR = 0.71, 95%CI:0.57-0.87) were related to hypertension. CONCLUSION: Prevalence of hypertension in Sichuan Tibetan was significantly higher than the national level with low rates of awareness, treatment, and control of hypertension. Intervention measurements are needed to change some unhealthy lifestyles, behaviors, and habits in this region. PMID- 27359365 TI - The Evolutionary Ecology of Plant Disease: A Phylogenetic Perspective. AB - An explicit phylogenetic perspective provides useful tools for phytopathology and plant disease ecology because the traits of both plants and microbes are shaped by their evolutionary histories. We present brief primers on phylogenetic signal and the analytical tools of phylogenetic ecology. We review the literature and find abundant evidence of phylogenetic signal in pathogens and plants for most traits involved in disease interactions. Plant nonhost resistance mechanisms and pathogen housekeeping functions are conserved at deeper phylogenetic levels, whereas molecular traits associated with rapid coevolutionary dynamics are more labile at branch tips. Horizontal gene transfer disrupts the phylogenetic signal for some microbial traits. Emergent traits, such as host range and disease severity, show clear phylogenetic signals. Therefore pathogen spread and disease impact are influenced by the phylogenetic structure of host assemblages. Phylogenetically rare species escape disease pressure. Phylogenetic tools could be used to develop predictive tools for phytosanitary risk analysis and reduce disease pressure in multispecies cropping systems. PMID- 27359366 TI - Phytophthora infestans: New Tools (and Old Ones) Lead to New Understanding and Precision Management. AB - New tools have revealed that migrations of Phytophthora infestans have been a dominant feature of the population biology of this pathogen for the past 50 years, and maybe for the past 170 years. We now have accurate information on the composition of many P. infestans populations. However, migration followed by selection can lead and has led to dramatically rapid changes in populations over large regions. Except for the highlands of central Mexico, many populations of P. infestans have probably been in flux over the past several decades. There is some evidence that this pathogen has different characteristics in the field than it does in the lab, and early field phenotypic analyses of hypotheses concerning fitness and pathogenicity would be beneficial. The newly available capacity to acquire and process vast amounts of weather and weather forecast data in combination with advancements in molecular diagnostics enables much greater precision in late blight management to produce recommendations that are site, host, and pathogen specific. PMID- 27359367 TI - Plant-Mediated Systemic Interactions Between Pathogens, Parasitic Nematodes, and Herbivores Above- and Belowground. AB - Plants are important mediators of interactions between aboveground (AG) and belowground (BG) pathogens, arthropod herbivores, and nematodes (phytophages). We highlight recent progress in our understanding of within- and cross-compartment plant responses to these groups of phytophages in terms of altered resource dynamics and defense signaling and activation. We review studies documenting the outcome of cross-compartment interactions between these phytophage groups and show patterns of cross-compartment facilitation as well as cross-compartment induced resistance. Studies involving soilborne pathogens and foliar nematodes are scant. We further highlight the important role of defense signaling loops between shoots and roots to activate a full resistance complement. Moreover, manipulation of such loops by phytophages affects systemic interactions with other plant feeders. Finally, cross-compartment-induced changes in root defenses and root exudates extend systemic defense loops into the rhizosphere, enhancing or reducing recruitment of microbes that induce systemic resistance but also affecting interactions with root-feeding phytophages. PMID- 27359368 TI - Developments in Plant Negative-Strand RNA Virus Reverse Genetics. AB - Twenty years ago, breakthroughs for reverse genetics analyses of negative-strand RNA (NSR) viruses were achieved by devising conditions for generation of infectious viruses in susceptible cells. Recombinant strategies have subsequently been engineered for members of all vertebrate NSR virus families, and research arising from these advances has profoundly increased understanding of infection cycles, pathogenesis, and complexities of host interactions of animal NSR viruses. These strategies also permitted development of many applications, including attenuated vaccines and delivery vehicles for therapeutic and biotechnology proteins. However, for a variety of reasons, it was difficult to devise procedures for reverse genetics analyses of plant NSR viruses. In this review, we discuss advances that have circumvented these problems and resulted in construction of a recombinant system for Sonchus yellow net nucleorhabdovirus. We also discuss possible extensions to other plant NSR viruses as well as the applications that may emanate from recombinant analyses of these pathogens. PMID- 27359370 TI - Molecular Soybean-Pathogen Interactions. AB - Soybean hosts a wide variety of pathogens that cause significant yield losses. The importance of soybean as a major oilseed crop has led to research focused on its interactions with pathogens, such as Soybean mosaic virus, Pseudomonas syringae, Phytophthora sojae, Phakopsora pachyrhizi, and Heterodera glycines. Pioneering work on soybean's interactions with these organisms, which represent the five major pathogen groups (viruses, bacteria, oomycetes, fungi, and nematodes), has contributed to our understanding of the molecular mechanisms underlying virulence and immunity. These mechanisms involve conserved and unique features that validate the need for research in both soybean and homologous model systems. In this review, we discuss identification of effectors and their functions as well as resistance gene-mediated recognition and signaling. We also point out areas in which model systems and recent advances in resources and tools have provided opportunities to gain deeper insights into soybean-pathogen interactions. PMID- 27359372 TI - Transcatheter valve-in-valve implantation for degenerated bioprosthetic aortic and mitral valves. AB - INTRODUCTION: Redo surgery still is the treatment of choice for degenerated bioprosthesis. However, as far as elderly patients with concomitant comorbidities are concerned, the standard reoperation carries additional operative risks and, therefore, minimally invasive procedures must be prioritized. AREAS COVERED: During the last ten years, transcatheter procedures in native valves have become a standard technique in several centers with excellent procedural and mid-term results. Similarly, implantation of transcatheter stent-valves within degenerated aortic and mitral bioprosthesis, the 'valve-in-valve' procedure (V-in-V), represents a valid alternative to redo surgery in patients with high-risk surgical profiles. New challenges for V-in-V are the transcatheter stent-valve deployment in hostile targets (stented bioprosthesis with externally mounted leaflets, stentless valves, small bioprostheses), and avoid complications as delayed atrial embolization of mitral implantation and V-in-V thrombosis. Moreover a continuous ameliorated design of the devices on the market and new transcatheter stent-valves are recently developed in order to improve the outcome and safety of V-in-V treatment. Expert commentary: We reviewed the clinical outcomes and the procedural details of published transcatheter aortic and mitral valve-in-valve series focusing, in particular, on data from the Valve-in-Valve International Data registry (VIVID), and we provide a practical guide for valve sizing and stent-valve positioning. PMID- 27359371 TI - Identification of 2-({[1-(4-Fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazol-3 yl]carbonyl}amino)tricyclo[3.3.1.13,7]decane-2-carboxylic Acid (NTRC-844) as a Selective Antagonist for the Rat Neurotensin Receptor Type 2. AB - Neurotensin receptor type 2 (NTS2) compounds display analgesic activity in animal pain models. We have identified the first high-affinity NTS2-selective antagonist (8) that is active in vivo. This study also revealed that the NTS2 FLIPR assay designation for a compound, agonist, partial agonist, and so forth, did not correlate with its in vivo activity as observed in the thermal tail-flick acute model of pain. This suggests that calcium mobilization is not the signaling pathway involved in NTS2-mediated analgesia as assessed by the thermal tail-flick model. Finally, we found a significant bias between rat and human for compound 9 in the NTS2 binding assay. PMID- 27359373 TI - Negatively Charged Lipid Membranes Catalyze Supramolecular Hydrogel Formation. AB - In this contribution we show that biological membranes can catalyze the formation of supramolecular hydrogel networks. Negatively charged lipid membranes can generate a local proton gradient, accelerating the acid-catalyzed formation of hydrazone-based supramolecular gelators near the membrane. Synthetic lipid membranes can be used to tune the physical properties of the resulting multicomponent gels as a function of lipid concentration. Moreover, the catalytic activity of lipid membranes and the formation of gel networks around these supramolecular structures are controlled by the charge and phase behavior of the lipid molecules. Finally, we show that the insights obtained from synthetic membranes can be translated to biological membranes, enabling the formation of gel fibers on living HeLa cells. PMID- 27359374 TI - Improved Photoelectrocatalytic Performance for Water Oxidation by Earth-Abundant Cobalt Molecular Porphyrin Complex-Integrated BiVO4 Photoanode. AB - An earth-abundant, low-cost cobalt porphyrin complex (CoTCPP) is designed as a molecular catalyst to work on three-dimensional BiVO4 film electrode for water oxidation for the first time. Under illumination of a 100 mW cm(-2) Xe lamp, the CoTCPP-functionalized BiVO4 photoanode exhibits a 2-fold enhancement in photocurrent density at 1.23 V vs RHE and nearly a 450 mV cathodic shift at 0.5 mA cm(-2) photocurrent density relative to bare BiVO4 in 0.1 M Na2SO4 (pH = 6.8). Simultaneously, stoichiometric oxygen and hydrogen are generated with a faradic efficiency of 80% over 4 h. The activity and stability of the BiVO4 photoanode are dramatically increased by molecular CoTCPP, giving rise to higher performance than previously reported noble metal ruthenium complex-modified BiVO4 photoanode. By using hydrogen peroxide as the hole scavenger, we demonstrate that molecular CoTCPP catalyst greatly suppresses the hole-electron recombination on the surface of BiVO4 semiconductor, which offers a promising route toward high efficiency, low cost, practical solar fuel generation device. PMID- 27359369 TI - Plant-Pathogen Effectors: Cellular Probes Interfering with Plant Defenses in Spatial and Temporal Manners. AB - Plants possess large arsenals of immune receptors capable of recognizing all pathogen classes. To cause disease, pathogenic organisms must be able to overcome physical barriers, suppress or evade immune perception, and derive nutrients from host tissues. Consequently, to facilitate some of these processes, pathogens secrete effector proteins that promote colonization. This review covers recent advances in the field of effector biology, focusing on conserved cellular processes targeted by effectors from diverse pathogens. The ability of effectors to facilitate pathogen entry into the host interior, suppress plant immune perception, and alter host physiology for pathogen benefit is discussed. Pathogens also deploy effectors in a spatial and temporal manner, depending on infection stage. Recent advances have also enhanced our understanding of effectors acting in specific plant organs and tissues. Effectors are excellent cellular probes that facilitate insight into biological processes as well as key points of vulnerability in plant immune signaling networks. PMID- 27359375 TI - Human papilloma virus infection in HIV-infected women in Belgium: implications for prophylactic vaccines within this subpopulation. AB - Although high-risk (HR) human papilloma virus (HPV) infection is the primary causative factor for cervical squamous intraepithelial lesions and invasive cervical cancer, the epidemiology of potentially HR (pHR) and low-risk HPV still remains to be elucidated in HIV-infected women. In addition, the synergistic potential of the multiplicity of HPV infections harboured renders it difficult to model the impact of vaccines. This cross-sectional analysis of HIV-infected women explores the epidemiology of abnormal cytology, thereby profiling and pairing pHR/HR HPV genotypes. This cross-sectional analysis reports the findings of 593 HIV-infected women, who underwent a cytological examination and HPV genotyping. A logistic regression model was fitted to adjust for age and coinfection with pHR/HR HPV genotypes. In the 143 women with abnormal cytology, a multiple pHR/HR HPV genotype prevalence of 64.1% [95% confidence interval (CI): 44.6-57.6%] was observed. A combined prevalence of HPV 16 and HPV 18 of 29.6% (95% CI: 22.2 37.8%) was found. HPV 6 and HPV 66 were found in two cases of low-grade squamous intraepithelial lesions as stand-alone genotypes and HPV 53 in a high-grade squamous intraepithelial lesion case. Pairing involving HPV 31 with HPV 16 and HPV 58 was found in high-grade squamous intraepithelial lesion cases. Significant associations were observed between abnormal cytology, multiple HPV, HPV 39 and HPV 53 [adjusted odds ratio (aOR): 2.02; P=0.01; 95% CI: 1.2-3.5; aOR: 3.8; P=0.01; 95% CI: 1.4-10.7; and aOR: 0.5; P=0.03; 95% CI: 0.2-0.9, respectively]. Coinfection with pHR/HR HPV genotypes HPV 39 and 53 was significantly associated with abnormal cytology. Research into the imputed role of HPV 31 in pairings, low risk and pHR HPV genotypes in HIV-infected women is warranted. PMID- 27359376 TI - Novel triterpenoids isolated from raisins exert potent antiproliferative activities by targeting mitochondrial and Ras/Raf/ERK signaling in human breast cancer cells. AB - Raisins are produced in many regions of the world and may be eaten raw or used in cooking, baking and brewing. Bioactivity-guided fractionation of raisins was used to determine the chemical identity of bioactive constituents. Seven triterpenoids, including three novel triterpenoids, were isolated and identified. The novel triterpenoids were elucidated to be 3beta,13beta-dihydroxy-12,13 dihydrooleanolic acid (1), 3beta,12beta,13beta-trihydroxy-12,13-dihydrooleanolic acid (2, TOA), and 3beta,13beta-dihydroxy-12,13-dihydroursolic acid (7), respectively. TOA showed the highest antiproliferative activity against MCF-7/DOX cells, with an EC50 value of 3.60 +/- 0.55 MUM. Compounds 1, 3 and 7 also exhibited potent antiproliferative activity against MCF-7/DOX cells, with an EC50 value of 7.10 +/- 0.65, 10.22 +/- 0.90 and 8.91 +/- 1.12 MUM. Compounds 1 and 2 also exhibited potent antioxidant activities. Moreover, the detailed cytotoxic mechanisms of TOA were investigated by targeting the mitochondrial and protein tyrosine kinase signaling (Ras/Raf/ERK). The results strongly demonstrated that the novel triterpenoids isolated from raisins could be promising candidates for therapy of breast cancer. PMID- 27359377 TI - Temozolomide induces the expression of the glioma Big Potassium (gBK) ion channel, while inhibiting fascin-1 expression: possible targets for glioma therapy. AB - OBJECTIVE: Temozolomide (TMZ) improves Glioblastoma Multiforme (GBM) patient survival. The invasive behavior of the glioma cells is the cause of GBM relapse. The glioma BK ion channel (gBK) may provide glioma cells with a mechanism to invade surrounding tissue. gBK contains epitopes that cytolytic T lymphocytes (CTLs) can recognize and kill glioma cells. Fascin-1 is an actin crosslinking molecule that supports microvilli; these membrane protrusions provide a physical defense against CTLs. TMZ was investigated to determine its effect on gBK and fascin-1 expression. RESEARCH DESIGN AND METHODS: Human glioma cells cultured in TMZ were analyzed for their altered mRNA and gBK protein levels by using quantitative real time PCR, immunostaining and cellular functional assays. RESULTS: TMZ slowed glioma cell growth and inhibited their transmigratory properties due to loss of fascin-1. TMZ induced increased gBK and HLA expression and allowed these TMZ-treated cells to become better targets for gBK-specific CTLs. CONCLUSIONS: Besides its traditional chemotherapeutic effect, TMZ can have four other targeted pathways: 1) slowed glioma cell growth; 2) inhibited glioma cell transmigration; 3) increased HLA-A2 and gBK tumor antigen production; 4) increased CTL-mediated cytolysis of the TMZ treated glioma cells due to the loss of their defensive membrane protrusions supported by fascin-1. PMID- 27359378 TI - The Ghost Collaborator. AB - Collaboration is increasingly important for researchers in all disciplines. Universities and funding bodies tend to prefer projects that involve interdisciplinarity, collaboration between different institutions, and international consortiums. Such projects can yield great benefits, but they also pose particular challenges for certain aspects of research integrity, and particularly for awarding credit and authorship. In this article, we describe and analyze the phenomenon of the ghost collaborator, who is initially fully involved and makes a full contribution to a project's design, but then finds him- or herself excluded from meetings and publications. PMID- 27359379 TI - Exploring the Lived Experience of Women Immediately Following Mastectomy: A Phenomenological Study. AB - BACKGROUND: In 2014, it is estimated that 232,670 new cases of breast cancer occurred in the United States. Unilateral or bilateral mastectomy is a frequently chosen option for treating this disease. OBJECTIVE: The purpose of this study was to explore, through an in-depth interview process, the lived experience of women immediately following mastectomy when they see their scars for the first time. METHODS: Purposeful sampling was used until saturation was reached. In-depth interviews were conducted with 10 women related to their mastectomy experience. The data were analyzed using a phenomenological approach. RESULTS: The following 8 themes emerged from the data; lasting impact, personal impact, relational impact, gratitude, support system, coping strategies, timing, and discomfort. CONCLUSIONS: The results of the study provide evidence that women face ongoing challenges following seeing their mastectomy scars for the first time that is not adequately addressed by healthcare professionals. IMPLICATIONS FOR PRACTICE: Nurses and other healthcare professionals need to gain a better understanding of the difficulties perceived by women following seeing the scars from mastectomy and implement strategies to assist in successful adaptation to the experience. PMID- 27362220 TI - Working memory in healthy aging and in Parkinson's disease: evidence of interference effects. AB - Focusing on relevant information while suppressing the irrelevant one are critical abilities for different cognitive processes. However, their functioning has been scarcely investigated in the working memory (WM) domain, in both healthy and pathological conditions. The present research aimed to study these abilities in aging and Parkinson's disease (PD), testing three groups of healthy participants (young, older and elderly) and one of PD patients, employing a new experimental paradigm. Results showed that the transient storing of irrelevant information in WM causes substantial interference effects, which were remarkable in elderly individuals on both response latency and accuracy. Interestingly, PD patients responded faster and were equally accurate compared to a matched control group. Taken together, findings confirm the existence of similar mechanisms for orienting attention inwards to WM contents or outwards to perceptual stimuli, and suggest the suitability of our task to assess WM functioning in both healthy aging and PD. PMID- 27362221 TI - Bright carbonate deposits as evidence of aqueous alteration on (1) Ceres. AB - The typically dark surface of the dwarf planet Ceres is punctuated by areas of much higher albedo, most prominently in the Occator crater. These small bright areas have been tentatively interpreted as containing a large amount of hydrated magnesium sulfate, in contrast to the average surface, which is a mixture of low albedo materials and magnesium phyllosilicates, ammoniated phyllosilicates and carbonates. Here we report high spatial and spectral resolution near-infrared observations of the bright areas in the Occator crater on Ceres. Spectra of these bright areas are consistent with a large amount of sodium carbonate, constituting the most concentrated known extraterrestrial occurrence of carbonate on kilometre wide scales in the Solar System. The carbonates are mixed with a dark component and small amounts of phyllosilicates, as well as ammonium carbonate or ammonium chloride. Some of these compounds have also been detected in the plume of Saturn's sixth-largest moon Enceladus. The compounds are endogenous and we propose that they are the solid residue of crystallization of brines and entrained altered solids that reached the surface from below. The heat source may have been transient (triggered by impact heating). Alternatively, internal temperatures may be above the eutectic temperature of subsurface brines, in which case fluids may exist at depth on Ceres today. PMID- 27362222 TI - Phenological sensitivity to climate across taxa and trophic levels. AB - Differences in phenological responses to climate change among species can desynchronise ecological interactions and thereby threaten ecosystem function. To assess these threats, we must quantify the relative impact of climate change on species at different trophic levels. Here, we apply a Climate Sensitivity Profile approach to 10,003 terrestrial and aquatic phenological data sets, spatially matched to temperature and precipitation data, to quantify variation in climate sensitivity. The direction, magnitude and timing of climate sensitivity varied markedly among organisms within taxonomic and trophic groups. Despite this variability, we detected systematic variation in the direction and magnitude of phenological climate sensitivity. Secondary consumers showed consistently lower climate sensitivity than other groups. We used mid-century climate change projections to estimate that the timing of phenological events could change more for primary consumers than for species in other trophic levels (6.2 versus 2.5 2.9 days earlier on average), with substantial taxonomic variation (1.1-14.8 days earlier on average). PMID- 27362223 TI - The nature of mutations induced by replication-transcription collisions. AB - The DNA replication and transcription machineries share a common DNA template and thus can collide with each other co-directionally or head-on. Replication transcription collisions can cause replication fork arrest, premature transcription termination, DNA breaks, and recombination intermediates threatening genome integrity. Collisions may also trigger mutations, which are major contributors to genetic disease and evolution. However, the nature and mechanisms of collision-induced mutagenesis remain poorly understood. Here we reveal the genetic consequences of replication-transcription collisions in actively dividing bacteria to be two classes of mutations: duplications/deletions and base substitutions in promoters. Both signatures are highly deleterious but are distinct from the previously well-characterized base substitutions in the coding sequence. Duplications/deletions are probably caused by replication stalling events that are triggered by collisions; their distribution patterns are consistent with where the fork first encounters a transcription complex upon entering a transcription unit. Promoter substitutions result mostly from head-on collisions and frequently occur at a nucleotide that is conserved in promoters recognized by the major sigma factor in bacteria. This substitution is generated via adenine deamination on the template strand in the promoter open complex, as a consequence of head-on replication perturbing transcription initiation. We conclude that replication-transcription collisions induce distinct mutation signatures by antagonizing replication and transcription, not only in coding sequences but also in gene regulatory elements. PMID- 27362224 TI - Lanthanum-catalysed synthesis of microporous 3D graphene-like carbons in a zeolite template. AB - Three-dimensional graphene architectures with periodic nanopores-reminiscent of zeolite frameworks-are of topical interest because of the possibility of combining the characteristics of graphene with a three-dimensional porous structure. Lately, the synthesis of such carbons has been approached by using zeolites as templates and small hydrocarbon molecules that can enter the narrow pore apertures. However, pyrolytic carbonization of the hydrocarbons (a necessary step in generating pure carbon) requires high temperatures and results in non selective carbon deposition outside the pores. Here, we demonstrate that lanthanum ions embedded in zeolite pores can lower the temperature required for the carbonization of ethylene or acetylene. In this way, a graphene-like carbon structure can be selectively formed inside the zeolite template, without carbon being deposited at the external surfaces. X-ray diffraction data from zeolite single crystals after carbonization indicate that electron densities corresponding to carbon atoms are generated along the walls of the zeolite pores. After the zeolite template is removed, the carbon framework exhibits an electrical conductivity that is two orders of magnitude higher than that of amorphous mesoporous carbon. Lanthanum catalysis allows a carbon framework to form in zeolite pores with diameters of less than 1 nanometre; as such, microporous carbon nanostructures can be reproduced with various topologies corresponding to different zeolite pore sizes and shapes. We demonstrate carbon synthesis for large-pore zeolites (FAU, EMT and beta), a one-dimensional medium pore zeolite (LTL), and even small-pore zeolites (MFI and LTA). The catalytic effect is a common feature of lanthanum, yttrium and calcium, which are all carbide-forming metal elements. We also show that the synthesis can be readily scaled up, which will be important for practical applications such as the production of lithium-ion batteries and zeolite-like catalyst supports. PMID- 27362225 TI - Cell division: A sticky problem for chromosomes. PMID- 27362226 TI - Ki-67 acts as a biological surfactant to disperse mitotic chromosomes. AB - Eukaryotic genomes are partitioned into chromosomes that form compact and spatially well-separated mechanical bodies during mitosis. This enables chromosomes to move independently of each other for segregation of precisely one copy of the genome to each of the nascent daughter cells. Despite insights into the spatial organization of mitotic chromosomes and the discovery of proteins at the chromosome surface, the molecular and biophysical bases of mitotic chromosome structural individuality have remained unclear. Here we report that the proliferation marker protein Ki-67 (encoded by the MKI67 gene), a component of the mitotic chromosome periphery, prevents chromosomes from collapsing into a single chromatin mass after nuclear envelope disassembly, thus enabling independent chromosome motility and efficient interactions with the mitotic spindle. The chromosome separation function of human Ki-67 is not confined within a specific protein domain, but correlates with size and net charge of truncation mutants that apparently lack secondary structure. This suggests that Ki-67 forms a steric and electrostatic charge barrier, similar to surface-active agents (surfactants) that disperse particles or phase-separated liquid droplets in solvents. Fluorescence correlation spectroscopy showed a high surface density of Ki-67 and dual-colour labelling of both protein termini revealed an extended molecular conformation, indicating brush-like arrangements that are characteristic of polymeric surfactants. Our study thus elucidates a biomechanical role of the mitotic chromosome periphery in mammalian cells and suggests that natural proteins can function as surfactants in intracellular compartmentalization. PMID- 27362228 TI - Phenology: Interactions of climate change and species. PMID- 27362229 TI - Neuroscience: In search of the memory molecule. PMID- 27362230 TI - Erratum: The bacterial DnaA-trio replication origin element specifies single stranded DNA initiator binding. PMID- 27362227 TI - Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. AB - The non-receptor protein tyrosine phosphatase SHP2, encoded by PTPN11, has an important role in signal transduction downstream of growth factor receptor signalling and was the first reported oncogenic tyrosine phosphatase. Activating mutations of SHP2 have been associated with developmental pathologies such as Noonan syndrome and are found in multiple cancer types, including leukaemia, lung and breast cancer and neuroblastoma. SHP2 is ubiquitously expressed and regulates cell survival and proliferation primarily through activation of the RAS-ERK signalling pathway. It is also a key mediator of the programmed cell death 1 (PD 1) and B- and T-lymphocyte attenuator (BTLA) immune checkpoint pathways. Reduction of SHP2 activity suppresses tumour cell growth and is a potential target of cancer therapy. Here we report the discovery of a highly potent (IC50 = 0.071 MUM), selective and orally bioavailable small-molecule SHP2 inhibitor, SHP099, that stabilizes SHP2 in an auto-inhibited conformation. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS-ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells in vitro and is efficacious in mouse tumour xenograft models. Together, these data demonstrate that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers. PMID- 27362231 TI - Mid-ocean-ridge seismicity reveals extreme types of ocean lithosphere. AB - Along ultraslow-spreading ridges, where oceanic tectonic plates drift very slowly apart, conductive cooling is thought to limit mantle melting and melt production has been inferred to be highly discontinuous. Along such spreading centres, long ridge sections without any igneous crust alternate with magmatic sections that host massive volcanoes capable of strong earthquakes. Hence melt supply, lithospheric composition and tectonic structure seem to vary considerably along the axis of the slowest-spreading ridges. However, owing to the lack of seismic data, the lithospheric structure of ultraslow ridges is poorly constrained. Here we describe the structure and accretion modes of two end-member types of oceanic lithosphere using a detailed seismicity survey along 390 kilometres of ultraslow spreading ridge axis. We observe that amagmatic sections lack shallow seismicity in the upper 15 kilometres of the lithosphere, but unusually contain earthquakes down to depths of 35 kilometres. This observation implies a cold, thick lithosphere, with an upper aseismic zone that probably reflects substantial serpentinization. We find that regions of magmatic lithosphere thin dramatically under volcanic centres, and infer that the resulting topography of the lithosphere-asthenosphere boundary could allow along-axis melt flow, explaining the uneven crustal production at ultraslow-spreading ridges. The seismicity data indicate that alteration in ocean lithosphere may reach far deeper than previously thought, with important implications towards seafloor deformation and fluid circulation. PMID- 27362233 TI - Corrigendum: Robust neuronal dynamics in premotor cortex during motor planning. PMID- 27362232 TI - Toremifene interacts with and destabilizes the Ebola virus glycoprotein. AB - Ebola viruses (EBOVs) are responsible for repeated outbreaks of fatal infections, including the recent deadly epidemic in West Africa. There are currently no approved therapeutic drugs or vaccines for the disease. EBOV has a membrane envelope decorated by trimers of a glycoprotein (GP, cleaved by furin to form GP1 and GP2 subunits), which is solely responsible for host cell attachment, endosomal entry and membrane fusion. GP is thus a primary target for the development of antiviral drugs. Here we report the first, to our knowledge, unliganded structure of EBOV GP, and high-resolution complexes of GP with the anticancer drug toremifene and the painkiller ibuprofen. The high-resolution apo structure gives a more complete and accurate picture of the molecule, and allows conformational changes introduced by antibody and receptor binding to be deciphered. Unexpectedly, both toremifene and ibuprofen bind in a cavity between the attachment (GP1) and fusion (GP2) subunits at the entrance to a large tunnel that links with equivalent tunnels from the other monomers of the trimer at the three-fold axis. Protein-drug interactions with both GP1 and GP2 are predominately hydrophobic. Residues lining the binding site are highly conserved among filoviruses except Marburg virus (MARV), suggesting that MARV may not bind these drugs. Thermal shift assays show up to a 14 degrees C decrease in the protein melting temperature after toremifene binding, while ibuprofen has only a marginal effect and is a less potent inhibitor. These results suggest that inhibitor binding destabilizes GP and triggers premature release of GP2, thereby preventing fusion between the viral and endosome membranes. Thus, these complex structures reveal the mechanism of inhibition and may guide the development of more powerful anti-EBOV drugs. PMID- 27362234 TI - Allosteric coupling from G protein to the agonist-binding pocket in GPCRs. AB - G-protein-coupled receptors (GPCRs) remain the primary conduit by which cells detect environmental stimuli and communicate with each other. Upon activation by extracellular agonists, these seven-transmembrane-domain-containing receptors interact with heterotrimeric G proteins to regulate downstream second messenger and/or protein kinase cascades. Crystallographic evidence from a prototypic GPCR, the beta2-adrenergic receptor (beta2AR), in complex with its cognate G protein, Gs, has provided a model for how agonist binding promotes conformational changes that propagate through the GPCR and into the nucleotide-binding pocket of the G protein alpha-subunit to catalyse GDP release, the key step required for GTP binding and activation of G proteins. The structure also offers hints about how G protein binding may, in turn, allosterically influence ligand binding. Here we provide functional evidence that G-protein coupling to the beta2AR stabilizes a 'closed' receptor conformation characterized by restricted access to and egress from the hormone-binding site. Surprisingly, the effects of G protein on the hormone-binding site can be observed in the absence of a bound agonist, where G protein coupling driven by basal receptor activity impedes the association of agonists, partial agonists, antagonists and inverse agonists. The ability of bound ligands to dissociate from the receptor is also hindered, providing a structural explanation for the G-protein-mediated enhancement of agonist affinity, which has been observed for many GPCR-G-protein pairs. Our data also indicate that, in contrast to agonist binding alone, coupling of a G protein in the absence of an agonist stabilizes large structural changes in a GPCR. The effects of nucleotide-free G protein on ligand-binding kinetics are shared by other members of the superfamily of GPCRs, suggesting that a common mechanism may underlie G-protein-mediated enhancement of agonist affinity. PMID- 27362235 TI - Conservation: The rainforest's 'do not disturb' signs. PMID- 27362236 TI - Anthropogenic disturbance in tropical forests can double biodiversity loss from deforestation. AB - Concerted political attention has focused on reducing deforestation, and this remains the cornerstone of most biodiversity conservation strategies. However, maintaining forest cover may not reduce anthropogenic forest disturbances, which are rarely considered in conservation programmes. These disturbances occur both within forests, including selective logging and wildfires, and at the landscape level, through edge, area and isolation effects. Until now, the combined effect of anthropogenic disturbance on the conservation value of remnant primary forests has remained unknown, making it impossible to assess the relative importance of forest disturbance and forest loss. Here we address these knowledge gaps using a large data set of plants, birds and dung beetles (1,538, 460 and 156 species, respectively) sampled in 36 catchments in the Brazilian state of Para. Catchments retaining more than 69-80% forest cover lost more conservation value from disturbance than from forest loss. For example, a 20% loss of primary forest, the maximum level of deforestation allowed on Amazonian properties under Brazil's Forest Code, resulted in a 39-54% loss of conservation value: 96-171% more than expected without considering disturbance effects. We extrapolated the disturbance mediated loss of conservation value throughout Para, which covers 25% of the Brazilian Amazon. Although disturbed forests retained considerable conservation value compared with deforested areas, the toll of disturbance outside Para's strictly protected areas is equivalent to the loss of 92,000-139,000 km2 of primary forest. Even this lowest estimate is greater than the area deforested across the entire Brazilian Amazon between 2006 and 2015 (ref. 10). Species distribution models showed that both landscape and within-forest disturbances contributed to biodiversity loss, with the greatest negative effects on species of high conservation and functional value. These results demonstrate an urgent need for policy interventions that go beyond the maintenance of forest cover to safeguard the hyper-diversity of tropical forest ecosystems. PMID- 27362237 TI - A core viral protein binds host nucleosomes to sequester immune danger signals. AB - Viral proteins mimic host protein structure and function to redirect cellular processes and subvert innate defenses. Small basic proteins compact and regulate both viral and cellular DNA genomes. Nucleosomes are the repeating units of cellular chromatin and play an important part in innate immune responses. Viral encoded core basic proteins compact viral genomes, but their impact on host chromatin structure and function remains unexplored. Adenoviruses encode a highly basic protein called protein VII that resembles cellular histones. Although protein VII binds viral DNA and is incorporated with viral genomes into virus particles, it is unknown whether protein VII affects cellular chromatin. Here we show that protein VII alters cellular chromatin, leading us to hypothesize that this has an impact on antiviral responses during adenovirus infection in human cells. We find that protein VII forms complexes with nucleosomes and limits DNA accessibility. We identified post-translational modifications on protein VII that are responsible for chromatin localization. Furthermore, proteomic analysis demonstrated that protein VII is sufficient to alter the protein composition of host chromatin. We found that protein VII is necessary and sufficient for retention in the chromatin of members of the high-mobility-group protein B family (HMGB1, HMGB2 and HMGB3). HMGB1 is actively released in response to inflammatory stimuli and functions as a danger signal to activate immune responses. We showed that protein VII can directly bind HMGB1 in vitro and further demonstrated that protein VII expression in mouse lungs is sufficient to decrease inflammation induced HMGB1 content and neutrophil recruitment in the bronchoalveolar lavage fluid. Together, our in vitro and in vivo results show that protein VII sequesters HMGB1 and can prevent its release. This study uncovers a viral strategy in which nucleosome binding is exploited to control extracellular immune signaling. PMID- 27362239 TI - Single versus Double Intrauterine Insemination in Controlled Ovarian Hyperstimulation Cycles: A Randomized Trial. AB - BACKGROUND: There are many factors that affect intrauterine insemination (IUI) success rate and identifying those factors can be helpful. This study aimed to investigate the single versus double IUI in controlled ovarian hyperstimulation cycles. METHODS: This is a randomized clinical trial with equal randomization (1:1) conducted on 580 women who underwent IUI in a private infertility clinic from May 2013 to November 2014 in Rasht, Iran. Women were randomly assigned to single (n = 290) or double (n = 290) IUI groups. Women in the single group underwent IUI performed 36 hours after human chorionic gonadotropin (HCG) administration. Women in the double group underwent two IUIs performed 18 and 40 hours after HCG administration. The main outcome was clinical pregnancy confirmed by evidence of fetal cardiac activity. Data were analyzed by SPSS software. Comparisons of frequencies were done using the Fisher exact test and Chi-square test. For comparing means between the two groups, the independent t-test was used. The P-value < 0.05 was considered to indicate statistical significance. RESULTS: Pregnancy rate was 11.7% (34/290) in the single IUI group and 13.4% (39/249) in the double IUI group. The difference between the two groups was not statistically significant (P = 0.617, OR = 1.17, 95% CI: 0.72 - 1.91). Also, we could not show significant difference between single and double IUI groups in different cause of infertility groups regarding the success rate. CONCLUSION: Based on findings, double versus single IUI did not increase the pregnancy rate of IUI and further investigations are recommended. PMID- 27362238 TI - Awareness, Treatment and Control of Pre-hypertension and Hypertension among Adults in Iran. AB - BACKGROUND: Hypertension is a major risk factor for non-communicable diseases. Yet, Nation-wide prevalence and trend reports in developing countries are sparsely available. METHODS: Data from three cycles of Survey of Risk Factors of Non-communicable Diseases (SuRFNCD) 2005 - 2011 were aggregated. In 2011, 8218 adults aged 25 - 70 years were enrolled. For trend analysis 68850, 4184, and 7416 adults aged 25 - 64 years were included from 2005, 2007, and 2011 surveys, respectively. Hypertension was defined as systolic blood pressure (SBP) >= 140 mmHg, diastolic blood pressure (DBP) >= 90 mmHg, or receiving anti-hypertensive medication. Pre-hypertension was defined as SBP between 120 - 139 or DBP between 80 - 89 mmHg. The status of awareness, non-pharmacologic treatment (management), pharmacologic treatment, and control (SBP < 140 mmHg, and DBP < 90 mmHg) among hypertensive individuals were also determined. RESULTS: 25.6% (95%CI: 23.5 - 27.5) of the adults aged 25 - 70 years had hypertension and 39.8% (95%CI: 37.8 - 41.9) had pre-hypertension. The prevalence of hypertension was greater among older adults (P < 0.001), women (P = 0.013), and urban-dwellers (P = 0.027). In 2005 - 2011, the proportion of adults with hypertension (25.7% to 24.1%) and pre hypertension (45.5% to 40.4%) significantly decreased. In 2011, rates for awareness, management, treatment, and control among hypertensives were 43.2% (95%CI: 40.0 - 46.4), 40.3% (95%CI: 37.0 - 43.6), 34.8% (95%CI: 31.5 - 38.2), and 38.6% (95%CI: 33.1 - 44.2), respectively. Over time, status of awareness, management, treatment and control was significantly improved and was more salient among men (P < 0.05 for all analyses). CONCLUSIONS: The prevalence of hypertension and pre-hypertension is gradually declining. Despite improvements in awareness, management, treatment and control, these decline rates are still low and initiative strategies need to be implemented to further improve the current status. PMID- 27362240 TI - Gender Differences in Major Dietary Patterns and Their Relationship with Cardio Metabolic Risk Factors in a Year before Coronary Artery Bypass Grafting (CABG) Surgery Period. AB - BACKGROUND: Previous studies reported the association between dietary patterns and prevalence of diabetes, cardiovascular disease and other chronic disease. However, there are no studies reporting major dietary patterns in patients awaiting coronary artery bypass graft surgery (CABG). The aim of this study was to obtain the major dietary patterns and their association with demographic, dietary factors and biochemical parameters in these patients. MATHERIALS AND METHODS: This was a cross-sectional study on 454 patients aged 35 - 80 years as candidates of CABG and hospitalized in the Tehran Heart Center. Anthropometric and demographic characteristics were obtained from all participants and a 138 item semi-quantitative food frequency questionnaire (FFQ) was used to evaluate dietary patterns by factor analysis. Biochemical parameters including HbA1c, serum lipids, hematocrit (HCT), albumin, creatinine and CRP were assessed by commercial laboratory methods. RESULTS: Five major dietary patterns, including: healthy, intermediate, neo-traditional, western and semi-Mediterranean patterns were extracted. Top quartile of healthy pattern was associated with higher educational attainment and lower serum low-density lipoprotein cholesterol (LDL), and total cholesterol (TC) in men, as well as higher high-density lipoprotein cholesterol (HDL) concentrations in women (P < 0.001). Individuals in top quartiles of intermediate and neo-traditional pattern were more likely to be male, had higher smoking and drinking habits, as well as the lower prevalence of diabetes, hyperlipidemia and hypertension (P < 0.05). They also had higher serum triglyceride (TG) concentrations. Patients in the western pattern also had a higher prevalence of a family history of cardiovascular disease and higher serum TG concentrations. Top quartiles of semi-Mediterranean pattern were associated with lower C-reactive protein (CRP) concentrations in women. CONCLUSIONS: There were five major dietary patterns using FFQ among patients awaiting CABG surgery. Significant associations were observed between major dietary patterns and risk of diabetes and hypertension. Top quartiles of healthy eating patterns were associated with lower cardio-metabolic risk factors. PMID- 27362241 TI - Determining Equity in Household's Health Care Payments in Hamedan Province, Iran. AB - BACKGROUND: Financial protection of household against the consequences of the health care expenditures is one of the most important functions of health care systems. The objective of this study was to determine the equity in health care payments and determining factors among households in Hamedan, a province in Iran. METHODS: In this cross-sectional study, 772 families of patients, who were being discharged from hospitals in Hamedan, were selected for study by using a stratified random sampling method. Required data regarding households' health and non-health expenditures were collected through World Health Organization standard questionnaire by interviews and observation method. RESULTS: According to the findings, 20.7% of households experienced catastrophic health expenditure. The incidence of impoverishment due to out-of-pocket payments for health care was 2.8% among studied households. The highest incidence rate of out-of-pocket health payment indices occurred in the first quintile (poorest or Q1). Variables such as having members under 6 years or over 60 years in household, household size, employment of household head, households' income quintile, existence of the disabled member in households and the education level of the household's head are the most important factors that affect the incidence of out-of-pocket health payment indices. CONCLUSION: There is considerable inequity in health care financing as well as households' health payments. This requires designing and implementing the operative and protective programs for understanding the important factors that affect equity in health financing, especially for poor households, against the unexpected health expenditures through the health care system. PMID- 27362242 TI - The Prevalence of Prostatic Stromal Tumor of Uncertain Malignant Potential in Specimens Diagnosed as Prostatic Hyperplasia. AB - BACKGROUND: Prostatic stromal tumors of uncertain malignant potential (STUMPs) are rare tumors arising from the specialized prostatic stroma. These tumors share certain histological and clinical features of benign prostatic hyperplasia, resulting in misdiagnosis of STUMP as prostatic hyperplasia. However, in contrast to prostatic hyperplasia, occasional cases have been documented to recur rapidly after resection and few of them have progressed to prostatic stromal sarcoma and distant metastasis. In this study, we aimed to estimate the prevalence of prostatic STUMP in specimens initially diagnosed as prostatic hyperplasia. MATHERIAL AND METHOD: A total of 702 consecutive pathology slides with a diagnosis of prostatic hyperplasia between 2009 to 2014 in specimens were obtained by prostatectomy or trans- urethral resection of the prostate. Those slides were submitted to Faghihi hospital, affiliated to Shiraz University of Medical Sciences, and were reviewed retrospectively in order to search the findings in favor of STUMP. RESULTS: Based on histological findings, STUMP was identified in 3 cases (0.43%), which revealed hypercellular stroma, infiltrating between the hyperplastic glands. Cells showed some degree of pleomorphism, nuclei with vesicular chromatin and few mitotic figures. No recurrence was reported in patients. CONCLUSION: Although STUMP can be histologically and clinically misdiagnosed as BPH, the differences in prognosis and treatment modalities highlight the importance of rendering the correct diagnosis. PMID- 27362243 TI - Management of Post-Intubation Tracheal Membrane Ruptures. AB - BACKGROUND: Iatrogenic tracheal rupture is a rare complication after intubation. Overinflation of the tracheal cuff was speculated to be a frequent cause of tracheal rupture. The surgical approach is a widespread treatment for tracheal ruptures. The aim of this study is to evaluate the results of conservative and surgical therapy approaches in tracheal rupture cases inflicted by tracheal intubation. METHODS: Data on 12 patients who experienced tracheal ruptures secondary to intubation were reviewed. The average age of the patients was 58 years (range of 38 to 81 years). Six patients were men and 6 patients were women. Four of the patients were performed thoracotomy for primary surgery and underwent surgical therapy. 8 patients were treated conservatively. The results of both approaches were evaluated. RESULTS: Patients, who underwent both conservative and surgical therapy, were completely recovered. There was no rupture originated complication or death. CONCLUSIONS: Both conservative and surgical therapies are appropriate for treatment of membranous tracheal rupture. PMID- 27362244 TI - Design and Validation of Real-Time PCR: Quantitative Diagnosis of Common Leishmania Species in Iran. AB - OBJECTIVE: Design and validation of Real-time PCR on the protected gene region ITS2 to quantify the parasite load in common leishmania (L) species. MATERIALS AND METHODS: Probe and primer were designed from the ITS2 region between the rRNA genes with minimum gene variation in three common leishmania species followed by a Real-time PCR using the Taq man probe method in the form of absolute quantification. A series of different concentrations of leishmania were analyzed. After the purified PCR product was successfully placed in a PTG19-T plasmid vector, specialized ITS2 region was cloned in this plasmid. In the last phase, the cloned gene was transferred to the Ecoli.Top10F bacteria. The standard plasmid was provided in 10(7) to 10(1) copies/rxn concentrations. The specification and clinical sensitivity of the data was analyzed using inter and intra scales. RESULTS: The probe and primer were designed using three species, including L. infantum, L. major, and L.tropica. Seven concentrations of purified parasite in culture media showed that the selected region for quantifying the parasite is suitable. Clinical and analytical specificity and sensitivity were both 100%, respectively. CONCLUSION: The Taq man method for the ITS2 region in leishmania is one the most sensitive diagnostic test for identifying the parasite load and is suggested as a tool for fast identification and quantification of species. PMID- 27362245 TI - A Comparative Study on the Adverse Reactions of Purified Chick Embryo Cell Vaccine (PCECV) and Purified Vero Cell Rabies Vaccine (PVRV). AB - OBJECTIVE: Human rabies is preventable by prompt application of post-exposure prophylaxis (PEP). The aim of this study was to compare the adverse reactions of purified vero cell rabies vaccine (PVRV) with purified chick embryo cell vaccine (PCECV) vaccination for the PEP. METHODS: In this double blind clinical trial study, 1449 people bitten by animals (279 females), were recruited from 9 different cities of Iran, and randomly assigned to receive intramuscular injections of the PVRV (n = 702) and PCECV (n = 747) vaccines in 5-dose regimen. The local and systemic adverse reactions were compared between two groups. RESULTS: The mean age was 26.8 years (SD, +/- 13.1 years) and 27.4 years (SD, +/ 13.9 years) in PVRV and PCECV group, respectively. Bites were most often located on the lower extremities in both groups. The most common local adverse reaction in both groups was pain at the injection site (4%). Most of the reported systemic adverse reactions were headache (2.5%) and fever (1.9%) in PCECV and PVRV group, respectively. The incidence of itching was higher in the PVRV group compared to the PCECV group (1% vs. 0.1%) (P < 0.05). There was no significant difference between two groups regarding systemic adverse reactions. CONCLUSION: The results of the present study indicated that PCECV vaccination was associated with fewer itching at the injection site. There was no significant difference between PCECV and PVRV vaccine regarding local and systemic adverse reactions. Therefore, the PCECV vaccine can be administered instead of PVRV, when our country encounters serious challenges in PVRV vaccine supply. PMID- 27362246 TI - The Role of Long Non-Coding RNAs in Breast Cancer. AB - Long non-coding RNA (lncRNA) genes are an important population of non-coding RNAs with defined key roles in normal development as well as tumorigenesis process. Evidences suggest that they can be classified as tumor suppressor genes or oncogenes according to their functions and expression pattern in tumoral tissues. They have been shown to regulate the plasticity of cancer stem cells. Their important roles in the regulation of cancer-related pathways in addition to deregulation of their expression in a number of cancers have suggested that they can be used as markers for cancer detection and prognosis, as well as targets for cancer treatment. Deregulation of a number of lncRNAs, such as HOTAIR, XIST, MALAT, and H19 has been detected in breast cancer samples and cell lines. In addition, the association between lncRNAs signature and breast cancer patients' survival has been assessed in various studies. Here, the expression patterns of lncRNAs in breast cancer, as well as their significance in prognosis and patient treatment are discussed. PMID- 27362247 TI - Imaging Findings for Bilateral Giant Vestibulocochlear Schwannoma. AB - Neurofibromatosis type 2 mostly develops with multiple neoplasms of the central and peripheral nervous system and is associated with ocular abnormalities. The presented case is a 19-year-old female patient with bilateral vestibulocochlear schwannomas in both pontocerebellar corners, intradural intra-extramedullary masses, and multiple neurofibromas in the spinal canal. The clinical picture for NF-2, also called central neurofibromatosis, is completely different from von Recklinghausen disease. Untreated bilateral vestibulocochlear schwannoma may cause hydrocephalus in NF-2, and lead to death. Therefore, it is recommended to carefully monitor and treat bilateral vestibulocochlear schwannoma in accordance with its stage. PMID- 27362248 TI - Hepatic Artery Pseudoaneurysm; Simple or Difficult to Diagnose? AB - Ruptured hepatic artery pseudoaneurysm (HAP) generally leads to the hemobilia and can be diagnosed by endoscopy. This condition mostly occurs after an iatrogenic trauma. The management of the HAP is still a big challenge. Due to an increased rate of HAP cases over the last decade, appropriate management is necessary for the optimal outcomes achievement. Here, we report a 59-year-old woman presenting with hematemesis, melena, hematochezia, and epigastric pain. The CT scan of the abdomen showed intrahepatic biliay dilation with hypodense material, probably a clot inside it. Subsequently, the patient was transferred to an angiography unit. Celiac artery angiography demonstrated a right hepatic artery pseudoaneurysm, which subsequently embolized. PMID- 27362249 TI - Photoclinic. PMID- 27362250 TI - Increased Density of Demodex Folliculorum May be Related to Additional Risk Factors. PMID- 27362251 TI - Unacceptability of Kyoto Global Consensus Report on Helicobacter Pylori Gastritis. PMID- 27362252 TI - Influence of Growth Characteristics of Induced Pluripotent Stem Cells on Their Uptake Efficiency for Layer-by-Layer Microcarriers. AB - Induced pluripotent stem cells (iPSCs) have the ability to differentiate into any specialized somatic cell type, which makes them an attractive tool for a wide variety of scientific approaches, including regenerative medicine. However, their pluripotent state and their growth in compact colonies render them difficult to access and, therefore, restrict delivery of specific agents for cell manipulation. Thus, our investigation focus was set on the evaluation of the capability of layer-by-layer (LbL) designed microcarriers to serve as a potential drug delivery system to iPSCs, as they offer several appealing advantages. Most notably, these carriers allow for the transport of active agents in a protected environment and for a rather specific delivery through surface modifications. As we could show, charge and mode of LbL carrier application as well as the size of the iPSC colonies determine the interaction with and the uptake rate by iPSCs. None of the examined conditions had an influence on iPSC colony properties such as colony morphology and size or maintenance of pluripotent properties. An overall interaction rate of LbL carriers with iPSCs of up to 20% was achieved. Those data emphasize the applicability of LbL carriers for stem cell research. Additionally, the potential use of LbL carriers as a promising delivery tool for iPSCs was contrasted to viral particles and liposomes. The identified differences among those delivery tools have substantiated our major conclusion that LbL carrier uptake rate is influenced by characteristic features of the iPSC colonies (most notably colony size) in addition to their surface charges. PMID- 27362253 TI - Sensitive detection of influenza viruses with Europium nanoparticles on an epoxy silica sol-gel functionalized polycarbonate-polydimethylsiloxane hybrid microchip. AB - In an effort to develop new tools for diagnosing influenza in resource-limited settings, we fabricated a polycarbonate (PC)-polydimethylsiloxane (PDMS) hybrid microchip using a simple epoxy silica sol-gel coating/bonding method and employed it in sensitive detection of influenza virus with Europium nanoparticles (EuNPs). The incorporation of sol-gel material in device fabrication provided functionalized channel surfaces ready for covalent immobilization of primary antibodies and a strong bonding between PDMS substrates and PC supports without increasing background fluorescence. In microchip EuNP immunoassay (uENIA) of inactivated influenza viruses, replacing native PDMS microchips with hybrid microchips allowed the achievement of a 6-fold increase in signal-to-background ratio, a 12-fold and a 6-fold decreases in limit-of-detection (LOD) in influenza A and B tests respectively. Using influenza A samples with known titers, the LOD of influenza uENIA on hybrid microchips was determined to be ~10(4) TCID50 titer/mL and 10(3)-10(4) EID50 titer/mL. A comparison test indicated that the sensitivity of influenza uENIA enhanced using the hybrid microchips even surpassed that of a commercial laboratory influenza ELISA test. In addition to the sensitivity improvement, assay variation was clearly reduced when hybrid microchips instead of native PDMS microchips were used in the uENIA tests. Finally, infectious reference viruses and nasopharyngeal swab patient specimens were successfully tested using MUENIA on hybrid microchip platforms, demonstrating the potential of this unique microchip nanoparticle assay in clinical diagnosis of influenza. Meanwhile, the tests showed the necessity of using nucleic acid confirmatory tests to clarify ambiguous test results obtained from prototype or developed point-of-care testing devices for influenza diagnosis. PMID- 27362254 TI - Pt NPs and DNAzyme functionalized polymer nanospheres as triple signal amplification strategy for highly sensitive electrochemical immunosensor of tumour marker. AB - Highly sensitive determination of tumour markers is the key for early diagnosis of cancer. Herein, triple signal amplification strategy resulting from polymer nanospheres, Pt NPs, and DNAzyme was proposed in the developed electrochemical immunosensor. First, electroactive polymer nanospheres were synthesized by infinite coordination polymerization of ferrocenedicarboxylic acid, which could generate strong electrochemical signals due to plentiful ferrocene molecules. Further, the polymer nanospheres were functionalized by Pt NPs and DNAzyme (hemin/G-quadruplex) with the ability of catalyzing H2O2, which contributes to enhance the electrochemical signals. The prepared conjugations were characterized by transmission electron microscope (TEM) and energy dispersive X-ray spectroscopy (EDX). And the process of preparation was monitored by zeta potential. Based on the sandwich-type immunoassay, the electrochemical immunosensor was constructed employing the conjugations as signal tags. Under optimal conditions, the DPV peak increased with the increasing of alpha fetal protein (AFP) concentration, and the linear range was from 0.1pgmL(-1) to 100ngmL(-1) with low detection limit of 0.086pgmL(-1). Meanwhile, the designed immunosensor exhibited excellent selectivity and anti-interference property, good reproducibility and stability. More importantly, there were no significant differences in analyzing real clinical samples between designed immunosensor and commercial ELISA. PMID- 27362256 TI - Diffusion of Immunoglobulin G in Shed Vaginal Epithelial Cells and in Cell-Free Regions of Human Cervicovaginal Mucus. AB - Human cervicovaginal mucus (CVM) is a viscoelastic gel containing a complex mixture of mucins, shed epithelial cells, microbes and macromolecules, such as antibodies, that together serve as the first line of defense against invading pathogens. Here, to investigate the affinity between IgG and different mucus constituents, we used Fluorescence Recovery After Photobleaching (FRAP) to measure the diffusion of IgG in fresh, minimally modified CVM. We found that CVM exhibits substantial spatial variations that necessitate careful selection of the regions in which to perform FRAP. In portions of CVM devoid of cells, FRAP measurements using different IgG antibodies and labeling methods consistently demonstrate that both exogenous and endogenous IgG undergo rapid diffusion, almost as fast as in saline, in good agreement with the rapid diffusion of IgG in mid-cycle endocervical mucus that is largely devoid of cells. This rapid diffusion indicates the interactions between secreted mucins and IgG must be very weak and transient. IgG also accumulated in cellular debris and shed epithelial cells that had become permeable to IgG, which may allow shed epithelial cells to serve as reservoirs of secreted IgG. Interestingly, in contrast to cell-free regions of CVM, the diffusion of cell-associated IgG was markedly slowed, suggesting greater affinity between IgG and cellular constituents. Our findings contribute to an improved understanding of the role of IgG in mucosal protection against infectious diseases, and may also provide a framework for using FRAP to study molecular interactions in mucus and other complex biological environments. PMID- 27362257 TI - Penetration of Gold Nanoparticles through Human Skin: Unraveling Its Mechanisms at the Molecular Scale. AB - Recent experimental studies suggest that nanosized gold nanoparticles (AuNPs) are able to penetrate into the deeper layer (epidermis and dermis) of rat and human skin. However, the mechanisms by which these AuNPs penetrate and disrupt the skin's lipid matrix are not well understood. In this study, we have used computer simulations to explore the translocation and the permeation of AuNPs through the model skin lipid membrane using both unconstrained and constrained coarse-grained molecular dynamics simulations. Each AuNP (1-6 nm) disrupted the bilayer packing and entered the interior of the bilayer rapidly (within 100 ns). It created a hydrophobic vacancy in the bilayer, which was mostly filled by skin constituents. Bigger AuNPs induced changes in the bilayer structure, and undulations were observed in the bilayer. The bilayer exhibited self-healing properties; it retained its original form once the simulation was run further after the removal of the AuNPs. Constrained simulation results showed that there was a trade-off between the kinetics and thermodynamics of AuNP permeation at a molecular scale. The combined effect of both resulted in a high permeation of small-sized AuNPs. The molecular-level information obtained through our simulations offers a very convenient method to design novel drug delivery systems and effective cosmetics. PMID- 27362255 TI - Improved Prefrontal Activity and Chewing Performance as Function of Wearing Denture in Partially Edentulous Elderly Individuals: Functional Near-Infrared Spectroscopy Study. AB - The purpose of this study was to elucidate the effects of wearing a denture on prefrontal activity during chewing performance. We specifically examined that activity in 12 elderly edentulous subjects [63.1+/-6.1 years old (mean +/- SD)] and 12 young healthy controls (22.1+/-2.3 years old) using functional near infrared spectroscopy (fNIRS) in order to evaluate the quality of prefrontal functionality during chewing performance under the conditions of wearing a denture and tooth loss, and then compared the findings with those of young healthy controls. fNIRS and electromyography were used simultaneously to detect prefrontal and masticatory muscle activities during chewing, while occlusal force and masticatory score were also examined by use of a food intake questionnaire. A significant increase in prefrontal activity was observed during chewing while wearing a denture, which was accompanied by increased masticatory muscle activity, occlusal force, and masticatory score, as compared with the tooth loss condition. Prefrontal activation during chewing while wearing a denture in the elderly subjects was not much different from that in the young controls. In contrast, tooth loss in the elderly group resulted in marked prefrontal deactivation, accompanied by decreased masticatory muscle activity, occlusal force, and masticatory score, as compared with the young controls. We concluded that intrinsic prefrontal activation during chewing with a denture may prevent prefrontal depression induced by tooth loss in elderly edentulous patients. PMID- 27362258 TI - DNA Barcoding of Malagasy Rosewoods: Towards a Molecular Identification of CITES Listed Dalbergia Species. AB - Illegal selective logging of tropical timber is of increasing concern worldwide. Madagascar is a biodiversity hotspot and home to some of the world's most sought after tropical timber species. Malagasy rosewoods belong to the genus Dalbergia (Fabaceae), which is highly diverse and has a pantropical distribution, but these timber species are among the most threatened as a consequence of intensive illegal selective logging and deforestation. Reliable identification of Dalbergia species from Madagascar is important for law enforcement but is almost impossible without fertile plant material, which is often unavailable during forest inventories or when attempting to identify logged trees of cut wood. DNA barcoding has been promoted as a promising tool for species identification in such cases. In this study we tested whether DNA barcoding with partial sequences of three plastid markers (matK, rbcL and trnL (UAA)) can distinguish between Dalbergia from Madagascar and from other areas of its distributional range, and whether Malagasy species can be distinguished from one another. Phylogenetic analyses revealed that the Malagasy Dalbergia species studied form two monophyletic groups, each containing two subgroups, only one of which corresponds to a single species. We characterized diagnostic polymorphisms in the three DNA barcoding markers that allow rapid discrimination between Dalbergia from Madagascar and from other areas of its distribution range. Species identification success based on individual barcoding markers or combinations was poor, whereas subgroup identification success was much higher (up to 98%), revealing both the value and limitations of a DNA barcoding approach for the identification of closely related Malagasy rosewoods. PMID- 27362259 TI - Profiling Analysis of Histone Modifications and Gene Expression in Lewis Lung Carcinoma Murine Cells Resistant to Anti-VEGF Treatment. AB - Tumor cells become resistant after long-term use of anti-VEGF (vascular endothelial growth factor) agents. Our previous study shows that treatment with a VEGF inhibitor (VEGF-Trap) facilitates to develop tumor resistance through regulating angiogenesis-related genes. However, the underlying molecular mechanisms remain elusive. Histone modifications as a key epigenetic factor play a critical role in regulation of gene expression. Here, we explore the potential epigenetic gene regulatory functions of key histone modifications during tumor resistance in a mouse Lewis lung carcinoma (LLC) cell line. We generated high resolution genome-wide maps of key histone modifications in sensitive tumor sample (LLC-NR) and resistant tumor sample (LLC-R) after VEGF-Trap treatment. Profiling analysis of histone modifications shows that histone modification levels are effectively predictive for gene expression. Composition of promoters classified by histone modification state is different between LLC-NR and LLC-R cell lines regardless of CpG content. Histone modification state change between LLC-NR and LLC-R cell lines shows different patterns in CpG-rich and CpG-poor promoters. As a consequence, genes with different level of CpG content whose gene expression level are altered are enriched in distinct functions. Notably, histone modification state change in promoters of angiogenesis-related genes consists with their expression alteration. Taken together, our findings suggest that treatment with anti-VEGF therapy results in extensive histone modification state change in promoters with multiple functions, particularly, biological processes related to angiogenesis, likely contributing to tumor resistance development. PMID- 27362261 TI - Retraction: Genetically Engineered Synthetic Miniaturized Versions of Plasmodium falciparum UvrD Helicase Are Catalytically Active. PMID- 27362260 TI - Colony Expansion of Socially Motile Myxococcus xanthus Cells Is Driven by Growth, Motility, and Exopolysaccharide Production. AB - Myxococcus xanthus, a model organism for studies of multicellular behavior in bacteria, moves exclusively on solid surfaces using two distinct but coordinated motility mechanisms. One of these, social (S) motility is powered by the extension and retraction of type IV pili and requires the presence of exopolysaccharides (EPS) produced by neighboring cells. As a result, S motility requires close cell-to-cell proximity and isolated cells do not translocate. Previous studies measuring S motility by observing the colony expansion of cells deposited on agar have shown that the expansion rate increases with initial cell density, but the biophysical mechanisms involved remain largely unknown. To understand the dynamics of S motility-driven colony expansion, we developed a reaction-diffusion model describing the effects of cell density, EPS deposition and nutrient exposure on the expansion rate. Our results show that at steady state the population expands as a traveling wave with a speed determined by the interplay of cell motility and growth, a well-known characteristic of Fisher's equation. The model explains the density-dependence of the colony expansion by demonstrating the presence of a lag phase-a transient period of very slow expansion with a duration dependent on the initial cell density. We propose that at a low initial density, more time is required for the cells to accumulate enough EPS to activate S-motility resulting in a longer lag period. Furthermore, our model makes the novel prediction that following the lag phase the population expands at a constant rate independent of the cell density. These predictions were confirmed by S motility experiments capturing long-term expansion dynamics. PMID- 27362263 TI - The symmetry-resolved electronic structure of 2H-WSe2(0 0 0 1). AB - The orbital symmetry of the band structure of 2H-WSe2(0 0 0 1) has been investigated by means of angle-resolved photoelectron spectroscopy (ARPES) and density functional theory (DFT). The WSe2(0 0 0 1) experimental band structure is found, by ARPES, to be significantly different for states of even and odd reflection parities along both the [Formula: see text]-[Formula: see text] and [Formula: see text]-[Formula: see text] lines, in good agreement with results obtained from DFT. The light polarization dependence of the photoemission intensities from the top of the valence band for bulk WSe2(0 0 0 1) is explained by the dominance of W 5[Formula: see text] states around the [Formula: see text] point and W 5d xy states around the [Formula: see text]-point, thus dominated, respectively, by states of even and odd symmetry, with respect to the [Formula: see text]-[Formula: see text] line. The splitting of the topmost valence band at [Formula: see text], due to spin-orbit coupling, is measured to be 0.49 +/- 0.01 eV, in agreement with the 0.48 eV value from DFT, and prior measurements for the bulk single crystal WSe2(0 0 0 1), albeit slightly smaller than the 0.513 +/ 0.01 eV observed for monolayer WSe2. PMID- 27362262 TI - Antibiotic Resistance in Escherichia coli from Pigs in Organic and Conventional Farming in Four European Countries. AB - Organic pig production differs in many ways from conventional production of pigs, e.g., in antibiotic use, herd structure, feeding regimes, access to outdoor areas and space allowance per pig. This study investigated if these differences result in a lower occurrence of antibiotic resistance in organic slaughter pigs in Denmark, France, Italy and Sweden. Samples were taken from the colon content and/or faeces and minimum inhibitory concentrations (MIC) of ten antibiotics were determined in isolates of Escherichia coli. In addition, the proportion of tetracycline (TET) resistant E. coli in colon content and/or faeces from individual pigs was determined. In all four countries the percentage resistance to ampicillin, streptomycin, sulphonamides or trimethoprim was significantly lower in E. coli from organic pigs. In France and Italy, the percentage of isolates resistant to chloramphenicol, ciprofloxacin, nalidixic acid or gentamicin was also significantly lower in the E. coli from organic pigs. Resistance to cefotaxime, was not found in any country. The percentage of E. coli isolates resistant to TET as well as the proportion of TET-resistant E. coli was significantly lower in organic than in conventional pigs, except in Sweden where TET-resistance was equally low in both production types. There were also differences between countries within production type in the percentage resistance to individual antibiotics as well as the proportion of TET-resistant E. coli with lower median proportions in Sweden and Denmark compared to France and Italy. The study shows that in each of the four countries resistance in intestinal E. coli was less common in organic than in conventional pigs, but that there were also large differences in resistance between countries within each production type, indicating that both country- and production-specific factors influence the occurrence of resistance. PMID- 27362264 TI - Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota. AB - Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as early colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in early life and the succession process and the evolution of the microbial community as a function of time and events occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to support the developing infant gut microbiome. PMID- 27362265 TI - Gamma Frequency and the Spatial Tuning of Primary Visual Cortex. AB - Visual stimulation produces oscillatory gamma responses in human primary visual cortex (V1) that also relate to visual perception. We have shown previously that peak gamma frequency positively correlates with central V1 cortical surface area. We hypothesized that people with larger V1 would have smaller receptive fields and that receptive field size, not V1 area, might explain this relationship. Here we set out to test this hypothesis directly by investigating the relationship between fMRI estimated population receptive field (pRF) size and gamma frequency in V1. We stimulated both the near-center and periphery of the visual field using both large and small stimuli in each location and replicated our previous finding of a positive correlation between V1 surface area and peak gamma frequency. Counter to our expectation, we found that between participants V1 size (and not PRF size) accounted for most of the variability in gamma frequency. Within participants we found that gamma frequency increased, rather than decreased, with stimulus eccentricity directly contradicting our initial hypothesis. PMID- 27362267 TI - Two-condition within-participant statistical mediation analysis: A path-analytic framework. AB - Researchers interested in testing mediation often use designs where participants are measured on a dependent variable Y and a mediator M in both of 2 different circumstances. The dominant approach to assessing mediation in such a design, proposed by Judd, Kenny, and McClelland (2001), relies on a series of hypothesis tests about components of the mediation model and is not based on an estimate of or formal inference about the indirect effect. In this article we recast Judd et al.'s approach in the path-analytic framework that is now commonly used in between-participant mediation analysis. By so doing, it is apparent how to estimate the indirect effect of a within-participant manipulation on some outcome through a mediator as the product of paths of influence. This path-analytic approach eliminates the need for discrete hypothesis tests about components of the model to support a claim of mediation, as Judd et al.'s method requires, because it relies only on an inference about the product of paths-the indirect effect. We generalize methods of inference for the indirect effect widely used in between-participant designs to this within-participant version of mediation analysis, including bootstrap confidence intervals and Monte Carlo confidence intervals. Using this path-analytic approach, we extend the method to models with multiple mediators operating in parallel and serially and discuss the comparison of indirect effects in these more complex models. We offer macros and code for SPSS, SAS, and Mplus that conduct these analyses. (PsycINFO Database Record PMID- 27362266 TI - Regulation and function of the SLC38A3/SNAT3 glutamine transporter. PMID- 27362268 TI - FISHtrees 3.0: Tumor Phylogenetics Using a Ploidy Probe. AB - Advances in fluorescence in situ hybridization (FISH) make it feasible to detect multiple copy-number changes in hundreds of cells of solid tumors. Studies using FISH, sequencing, and other technologies have revealed substantial intra-tumor heterogeneity. The evolution of subclones in tumors may be modeled by phylogenies. Tumors often harbor aneuploid or polyploid cell populations. Using a FISH probe to estimate changes in ploidy can guide the creation of trees that model changes in ploidy and individual gene copy-number variations. We present FISHtrees 3.0, which implements a ploidy-based tree building method based on mixed integer linear programming (MILP). The ploidy-based modeling in FISHtrees includes a new formulation of the problem of merging trees for changes of a single gene into trees modeling changes in multiple genes and the ploidy. When multiple samples are collected from each patient, varying over time or tumor regions, it is useful to evaluate similarities in tumor progression among the samples. Therefore, we further implemented in FISHtrees 3.0 a new method to build consensus graphs for multiple samples. We validate FISHtrees 3.0 on a simulated data and on FISH data from paired cases of cervical primary and metastatic tumors and on paired breast ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). Tests on simulated data show improved accuracy of the ploidy based approach relative to prior ploidyless methods. Tests on real data further demonstrate novel insights these methods offer into tumor progression processes. Trees for DCIS samples are significantly less complex than trees for paired IDC samples. Consensus graphs show substantial divergence among most paired samples from both sets. Low consensus between DCIS and IDC trees may help explain the difficulty in finding biomarkers that predict which DCIS cases are at most risk to progress to IDC. The FISHtrees software is available at ftp://ftp.ncbi.nih.gov/pub/FISHtrees. PMID- 27362269 TI - Reverse Regulatory Pathway (H2S / PGE2 / MMP) in Human Aortic Aneurysm and Saphenous Vein Varicosity. AB - Hydrogen sulfide (H2S) is a mediator with demonstrated protective effects for the cardiovascular system. On the other hand, prostaglandin (PG)E2 is involved in vascular wall remodeling by regulating matrix metalloproteinase (MMP) activities. We tested the hypothesis that endogenous H2S may modulate PGE2, MMP-1 activity and endogenous tissue inhibitors of MMPs (TIMP-1/-2). This regulatory pathway could be involved in thinning of abdominal aortic aneurysm (AAA) and thickening of saphenous vein (SV) varicosities. The expression of the enzyme responsible for H2S synthesis, cystathionine-gamma-lyase (CSE) and its activity, were significantly higher in varicose vein as compared to SV. On the contrary, the endogenous H2S level and CSE expression were lower in AAA as compared to healthy aorta (HA). Endogenous H2S was responsible for inhibition of PGE2 synthesis mostly in varicose veins and HA. A similar effect was observed with exogenous H2S and consequently decreasing active MMP-1/TIMP ratios in SV and varicose veins. In contrast, in AAA, higher levels of PGE2 and active MMP-1/TIMP ratios were found versus HA. These findings suggest that differences in H2S content in AAA and varicose veins modulate endogenous PGE2 production and consequently the MMP/TIMP ratio. This mechanism may be crucial in vascular wall remodeling observed in different vascular pathologies (aneurysm, varicosities, atherosclerosis and pulmonary hypertension). PMID- 27362270 TI - Medical Abortion Provided by Nurse-Midwives or Physicians in a High Resource Setting: A Cost-Effectiveness Analysis. AB - OBJECTIVE: The objective of the present study is to calculate the cost effectiveness of early medical abortion performed by nurse-midwifes in comparison to physicians in a high resource setting where ultrasound dating is part of the protocol. Non-physician health care professionals have previously been shown to provide medical abortion as effectively and safely as physicians, but the cost effectiveness of such task shifting remains to be established. STUDY DESIGN: A cost effectiveness analysis was conducted based on data from a previously published randomized-controlled equivalence study including 1180 healthy women randomized to the standard procedure, early medical abortion provided by physicians, or the intervention, provision by nurse-midwifes. A 1.6% risk difference for efficacy defined as complete abortion without surgical interventions in favor of midwife provision was established which means that for every 100 procedures, the intervention treatment resulted in 1.6 fewer incomplete abortions needing surgical intervention than the standard treatment. The average direct and indirect costs and the incremental cost-effectiveness ratio (ICER) were calculated. The study was conducted at a university hospital in Stockholm, Sweden. RESULTS: The average direct costs per procedure were EUR 45 for the intervention compared to EUR 58.3 for the standard procedure. Both the cost and the efficacy of the intervention were superior to the standard treatment resulting in a negative ICER at EUR -831 based on direct costs and EUR -1769 considering total costs per surgical intervention avoided. CONCLUSION: Early medical abortion provided by nurse-midwives is more cost-effective than provision by physicians. This evidence provides clinicians and decision makers with an important tool that may influence policy and clinical practice and eventually increase numbers of abortion providers and reduce one barrier to women's access to safe abortion. PMID- 27362272 TI - Unforgotten: love and the culture of dementia care in India, by Bianca Brijnath. PMID- 27362271 TI - Usefulness of Bronchoscopic Probe-Based Confocal Laser Endomicroscopy in the Diagnosis of Pneumocystis jirovecii Pneumonia. AB - BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) is a novel technique that provides in vivo microscopic imaging of the distal lung. We hypothesized that the intra-alveolar exudates characterizing Pneumocystis jirovecii pneumonia (PJP) can be identified by pCLE in vivo and help in its diagnosis. OBJECTIVES: We aimed to assess the usefulness of pCLE for the in vivo diagnosis of PJP. METHODS: Thirty-two human immunodeficiency virus (HIV)-positive patients with new pulmonary infiltrates and fever were studied using pCLE. Real-time alveolar images were recorded during the bronchoscopy for off-line analysis by two independent observers. Bronchoalveolar lavage samples were also obtained and processed for microbiology and cytological evaluation, including Grocott stain for P. jirovecii. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of pCLE for the diagnosis of PJP in these patients were calculated. RESULTS: Fourteen patients (44%) were confirmed to have PJP by cultures/staining. pCLE was well tolerated in all patients. It identified intra-alveolar exudates in 13 of them (41%), where 11 of them (85%) had positive Grocott stain for P. jirovecci, with 93% concordance between observers. Sensitivity, specificity, PPV and NPV of pCLE for the diagnosis of PJP were 79, 89, 85 and 84%, respectively. In smokers, these figures improved to be 92, 88, 85 and 94%. CONCLUSIONS: pCLE is a quick and safe procedure for on-site diagnosis of PJP in HIV+ patients with excellent specificity and sensitivity mainly in smokers. PMID- 27362274 TI - Evaluation of standardized sample collection, packaging, and decontamination procedures to assess cross-contamination potential during Bacillus anthracis incident response operations. AB - Sample collection procedures and primary receptacle (sample container and bag) decontamination methods should prevent contaminant transfer between contaminated and non-contaminated surfaces and areas during bio-incident operations. Cross contamination of personnel, equipment, or sample containers may result in the exfiltration of biological agent from the exclusion (hot) zone and have unintended negative consequences on response resources, activities and outcomes. The current study was designed to: (1) evaluate currently recommended sample collection and packaging procedures to identify procedural steps that may increase the likelihood of spore exfiltration or contaminant transfer; (2) evaluate the efficacy of currently recommended primary receptacle decontamination procedures; and (3) evaluate the efficacy of outer packaging decontamination methods. Wet- and dry-deposited fluorescent tracer powder was used in contaminant transfer tests to qualitatively evaluate the currently-recommended sample collection procedures. Bacillus atrophaeus spores, a surrogate for Bacillus anthracis, were used to evaluate the efficacy of spray- and wipe-based decontamination procedures. Both decontamination procedures were quantitatively evaluated on three types of sample packaging materials (corrugated fiberboard, polystyrene foam, and polyethylene plastic), and two contamination mechanisms (wet or dry inoculums). Contaminant transfer results suggested that size appropriate gloves should be worn by personnel, templates should not be taped to or removed from surfaces, and primary receptacles should be selected carefully. The decontamination tests indicated that wipe-based decontamination procedures may be more effective than spray-based procedures; efficacy was not influenced by material type but was affected by the inoculation method. Incomplete surface decontamination was observed in all tests with dry inoculums. This study provides a foundation for optimizing current B. anthracis response procedures to minimize contaminant exfiltration. PMID- 27362275 TI - Risk of transfusion-transmitted chikungunya infection and efficacy of blood safety implementation measures: experience from the 2009 epidemic in Songkhla Province, Thailand. AB - BACKGROUND: To date, neither is there a standard guideline for maintaining a safe blood supply during a chikungunya fever (CHIKF) outbreak nor has a study been performed on actual transfusion-transmitted CHIKF to recipients. This study estimated the potential incidence of transfusion-transmitted CHIKF and compared the efficacies of various blood safety intervention strategies to mitigate the transfusion-transmitted CHIKF risk. STUDY DESIGN AND METHODS: A Web-based tool named the European Up-Front Risk Assessment Tool (EUFRAT) was used to estimate the risk of transfusion-transmitted CHIKF using data inputs from the 2009 Songkhla epidemic in Thailand. RESULTS: The mean and maximal risks of viremic donations during the entire epidemic period were estimated to be 0.9 (95% confidence interval [CI], 0.0-2.7) and 4.8 (95% CI, 0.5-9.1), respectively. This meant that the potential risk of transfusion-transmitted CHIKF to recipients receiving all infective end products in the absence of blood safety measures was from 10.9 (95% CI, 1.8-20.4) to 57.6 (95% CI, 36.4-79.5). Based on experience from the 2009 Thai epidemic, the proportion of 10% asymptomatic cases, for instance, with predonation screening for CHIKF-related symptoms and follow-up observation in donors at risk was estimated to be 88.4% (95% CI, 69.9%-100.0%) to 99.1% (95% CI, 79.6%-100.0%) effective in reducing this transfusion risk compared to 83.7% (95% CI, 65.8%-100.0%) to 90.7% (95% CI, 72.1%-100.0%) by predonation screening for donors at risk of chikungunya virus infection alone. CONCLUSION: This study suggests that prompt blood screening measures can reduce the risk of transfusion-transmitted CHIKF and maintain a safe blood supply during an outbreak. PMID- 27362276 TI - Ndt80 activates the meiotic ORC1 transcript isoform and SMA2 via a bi-directional middle sporulation element in Saccharomyces cerevisiae. AB - The origin of replication complex subunit ORC1 is important for DNA replication. The gene is known to encode a meiotic transcript isoform (mORC1) with an extended 5'-untranslated region (5'-UTR), which was predicted to inhibit protein translation. However, the regulatory mechanism that controls the mORC1 transcript isoform is unknown and no molecular biological evidence for a role of mORC1 in negatively regulating Orc1 protein during gametogenesis is available. By interpreting RNA profiling data obtained with growing and sporulating diploid cells, mitotic haploid cells, and a starving diploid control strain, we determined that mORC1 is a middle meiotic transcript isoform. Regulatory motif predictions and genetic experiments reveal that the activator Ndt80 and its middle sporulation element (MSE) target motif are required for the full induction of mORC1 and the divergently transcribed meiotic SMA2 locus. Furthermore, we find that the MSE-binding negative regulator Sum1 represses both mORC1 and SMA2 during mitotic growth. Finally, we demonstrate that an MSE deletion strain, which cannot induce mORC1, contains abnormally high Orc1 levels during post-meiotic stages of gametogenesis. Our results reveal the regulatory mechanism that controls mORC1, highlighting a novel developmental stage-specific role for the MSE element in bi directional mORC1/SMA2 gene activation, and correlating mORC1 induction with declining Orc1 protein levels. Because eukaryotic genes frequently encode multiple transcripts possessing 5'-UTRs of variable length, our results are likely relevant for gene expression during development and disease in higher eukaryotes. PMID- 27362277 TI - Echocardiographic Assessment of Left Atrial Size and Function in Warmblood Horses: Reference Intervals, Allometric Scaling, and Agreement of Different Echocardiographic Variables. AB - BACKGROUND: Echocardiographic assessment of left atrial (LA) size and function in horses is not standardized. OBJECTIVES: The aim of this study was to establish reference intervals for echocardiographic indices of LA size and function in Warmblood horses and to provide proof of concept for allometric scaling of variables and for the clinical use of area-based indices. ANIMALS: Thirty-one healthy Warmblood horses and 91 Warmblood horses with a primary diagnosis of mitral regurgitation (MR) or aortic regurgitation (AR). METHODS: Retrospective study. Echocardiographic indices of LA size and function were measured and scaled to body weight (BWT). Reference intervals were calculated, the influence of BWT, age, and valvular regurgitation on LA size and function was investigated and agreement between different measurements of LA size was assessed. RESULTS: Allometric scaling of variables of LA size allowed for correction of differences in BWT. Indices of LA size documented LA enlargement with moderate and severe MR and AR, whereas most indices of LA mechanical function were not significantly altered by valvular regurgitation. Different indices of LA size were in fair to good agreement but still lead to discordant conclusions with regard to assessment of LA enlargement in individual horses. CONCLUSIONS AND CLINICAL IMPORTANCE: Allometric scaling of echocardiographic variables of LA size is advised to correct for differences in BWT among Warmblood horses. Assessment of LA dimensions should be based on an integrative approach combining subjective evaluation and assessment of multiple measurements, including area-based variables. The clinical relevance of indices of LA mechanical function remains unclear when used in horses with mitral or aortic regurgitation. PMID- 27362278 TI - Variability of gait speed during six minutes walking test in COPD and cystic fibrosis patients. AB - BACKGROUND: Recently, gait speed reached an increasing importance in the management of respiratory patients. The aim of this retrospective study was to compare walking speed and physiological adaptations during the 6MWT in COPD and CF patients. METHODS: 6MWT performed by COPD and CF patients were retrospectively reviewed. Global and sequential walking speeds were measured on six minutes and every sequence of two minutes respectively. Heart rate, oxygen saturation and dyspnea were analyzed. RESULTS: 78 and 246 tests from CF and COPD patients were reviewed respectively. FEV1 (52.3 vs 56.2% pred) and FVC (72.5 vs 73.8% pred) were similar between both diseases. However, 6MWT in patients with CF were characterized by significantly higher heart rate, global walking speed and walking distance (+68%) while dyspnea evolutions and the proportions of patients presenting walking speed decline over the 6min were significantly lower. CONCLUSION: Walking speed and cardio-respiratory parameters evolution during 6MWT differ between COPD and CF patients. PMID- 27362279 TI - Lower leg compensatory strategies during performance of a step up and over task in patient six-months after total knee arthroplasty. AB - The purpose of this study was to assess the ankle, knee, and hip joint contributions to the total support moment (TSM) and the activation patterns of muscles in the lower leg in patients after total knee arthroplasty (TKA) and healthy older adults during the step up and over task. Moreover, the relationship between quadriceps strength and knee contribution to TSM was measured. Twenty patients six-months after TKA and twenty healthy controls were recruited for this study. Motion and surface electromyographic (EMG) analyses were performed during a step up and over task. Biomechanics and EMG variables were compared between groups using ANCOVA models with movement speed as covariate. Patients after TKA had reduced contribution to the TSM from the knee joint, and greater contribution from the hip and ankle joints, possibly to compensate for the reduced contribution at the knee. No consistent differences of EMG activation or co contraction were found between groups. Patients with stronger quadriceps had significantly higher knee contribution to TSM during the lowering phase of the task. The results of this study suggest that patients after TKA may use compensatory strategies at the hip and ankle joints to safely perform the step up and over task. Patients may rely on the force generating ability of the quadriceps during the lowering phase as they are not able to compensate with other joints of the lower extremity during this phase of the task. PMID- 27362280 TI - Unmasking the true identity in neuron differentiation. PMID- 27362281 TI - [Mn(III)Mn(IV)2Mo14O56](17-): A Mixed-Valence Meso-Polyoxometalate Anion Encapsulated by a 64-Nuclearity Silver Cluster. AB - A 64-nuclearity silver cluster encapsulating a unique POM anion [Mn(III)Mn(IV)2Mo14O56](17-) has been synthesized. The formation of the templating core performs a reassembly process for increasing nuclearities from {MnMo9} to {Mn3Mo14}. It represents a rare inorganic meso anion containing mixed valent Mn that is built up by d-{Mn(IV)Mo7} and l-{Mn(IV)Mo7} units connecting together through a {Mn(III)} fragment. PMID- 27362282 TI - Access to diagnostic tests during GP out-of-hours care: A cross-sectional study of all GP out-of-hours services in the Netherlands. AB - BACKGROUND: In general practice, excluding serious conditions is one of the cornerstones of the consultation. Diagnostic tests are widely used to assist the decision-making process in these cases. Little is known about general practitioners' (GPs) access to diagnostic tests at GP out-of-hours services. OBJECTIVES: To determine GPs' access to diagnostic tests-imaging, function tests, laboratory tests, and point-of-care tests (POCT)-during GP out-of-hours care and to assess whether access to diagnostic facilities differs between services located adjacent to or separate from an accident and emergency (A&E) department. METHODS: Cross-sectional survey of all 117 GP out-of-hours services in the Netherlands in 2014. RESULTS: One-hundred-seventeen GP out-of-hours services participated in the survey; response rate 100%. Access to diagnostic tests during GP out-of-hours care varied across services, although generally there was limited access. Electrocardiography was available in 26% (30/117) of all services, conventional radiography in 19% (22/117), laboratory tests between 37% (43/117) and 65% (76/117). All services had glucose POCT and urine dipstick tests available while none utilized troponin POCT. We observed no relevant differences in access to diagnostic tests between services adjacent to or separate from an A&E department. CONCLUSION: GPs in the Netherlands had limited and varying access to diagnostic tests during GP out-of-hours care in 2014. Out-of-hours services adjacent to A&E departments do not offer wider access to diagnostic tests. Further research on the accessibility of diagnostic tests in other European countries with similar and different GP out-of-hours care systems could shed further light on the effects of accessibility to diagnostic tests. [Box: see text]. PMID- 27362284 TI - Mass Spectrometric Mapping of the DNA Adductome as a Means to Study Genotoxin Exposure, Metabolism, and Effect. AB - Covalent binding of endo- or exogenous chemicals to DNA results in the formation of DNA adducts which are reflective of exposure of the human body to DNA-damaging molecules and their metabolic pathways. The study of DNA adduct types and levels in human tissue therefore offers an interesting tool in several fields of research, including toxicology and cancer epidemiology. Over the years, a range of techniques and methods have been developed to study the formation of endo- and exogenous DNA adducts. However, for the simultaneous detection, identification and quantification of both known and unknown DNA adducts, mass spectrometry (MS) is deemed to be the most promising technique. In this perspective, we focus on the analysis of multiple DNA adducts within a sample with the emphasis on untargeted analysis. The advantageous use of MS methodologies for DNA adductome mapping is discussed comprehensively with relevant field examples. In addition, several aspects of study design, sample pretreatment, and analysis are addressed as these factors significantly affect the reliability of DNA adductomics studies. PMID- 27362286 TI - Quantum Chemical Studies of the Substituent Effect on the Reaction of Carbonyl Oxime with Amine. AB - The reaction of the two different substitue carbonyl oximes (isonitrosoacetylnaphthaline, inanH and nitro-isonitrosoacetophenone, ninapH) with two different amines (1-phenylethanol amine, pea, and ethanol amine, ea) was carried out and characterized by elemental analyses, IR, and (1)H and (13)C NMR spectroscopic methods. As a result of these experimental studies, two different levels for all reactions were determined: (I) formation of imine oxime and (II) rearrangement of imine oxime or formation of amido alcohol. After a mechanism was suggested for all of these reactions, the reaction mechanism of carbonyl oxime with amine was first studied by means of the B3LYP/6-311G(d,p) method. Because of the deficiency of density functional theory (DFT) on dispersion effects, the wB97X-D/6-311G(d,p) method, which includes dispersion correction, was used to obtain the reaction heat and free energy barriers to explain why the formation (imine oxime) and unexpected rearrangement products (amido alcohol) occurred or did not occur. The statistical thermodynamic method was used to obtain the changes in thermodynamic properties of the studied molecules between 100 and 500 K. From a kinetic viewpoint, the slowest step of the reactions is the IN1-TS2-IN2 step, which determines the steps of the reaction kinetics. In addition, spectroscopic properties such as vibrational and NMR chemical shifts were studied for all of the molecules. The frontier molecular orbitals (FMOs), highest occupied molecular orbitals (HOMOs), and lowest unoccupied molecular orbitals (LUMOs) were monitored for all of the molecules. PMID- 27362285 TI - Design, synthesis, and pharmacological evaluation of 5-oxo-1,2,4-oxadiazole derivatives as AT1 antagonists with antihypertension activities. AB - A series of new 5-oxo-1,2,4-oxadiazole derivatives with 1, 4-disubsituted or 1, 5 disubsituted indole group was designed, synthesized, and pharmacologically evaluated. These derivatives displayed high affinities to the AT1 receptor at the same order of magnitude to losartan. The methyl ester with 1, 4-disubsituted indole group, 1 (5.01 +/- 1.67 nM) showed high antihypertension activity on spontaneously hypertensive rats (SHRs). Its maximal response lowered 30 mmHg of mean blood pressure (MBP) at 10 mg/kg after oral administration, which was better than irbesartan, and the antihypertensive effect lasted beyond 24 h. These results made 1 deserve further investigation. PMID- 27362288 TI - Factitious Graves' Disease Due to Biotin Immunoassay Interference-A Case and Review of the Literature. AB - CONTEXT: Biotin (vitamin B7) is an essential co-factor for four carboxylases involved in fatty acid metabolism, leucine degradation, and gluconeogenesis. The recommended daily intake (RDI) of biotin is approximately 30 MUg per day. Low moderate dose biotin is a common component of multivitamin preparations, and high dose biotin (10 000 times RDI) has been reported to improve clinical outcomes and quality of life in patients with progressive multiple sclerosis. Biotin is also a component of immunoassays, and supplementation may cause interference in both thyroid and non-thyroid immunoassays. OBJECTIVE: To assess whether biotin ingestion caused abnormal thyroid function tests (TFTs) in a patient through assay interference. DESIGN: We report a patient with biotin-associated abnormal TFTs and a systematic review of the literature. SETTING: A tertiary endocrine service in Hamilton, New Zealand. RESULTS: The patient had markedly abnormal TFTs that did not match the clinical context. After biotin cessation, TFTs normalized far more rapidly than possible given the half-life of T4, consistent with assay interference by biotin. Multiple other analytes also tested abnormal in the presence of biotin. CONCLUSION: Biotin ingested in moderate to high doses can cause immunoassay interference. Depending on the assay format, biotin interference can result in either falsely high or low values. Interference is not limited to thyroid tests and has the potential to affect a wide range of analytes. It is important for clinicians to be aware of this interaction to prevent misdiagnosis and inappropriate treatment. PMID- 27362287 TI - Increased hydrogen peroxide impairs angiotensin II contractions of afferent arterioles in mice after renal ischaemia-reperfusion injury. AB - AIM: Renal ischaemia-reperfusion injury (IRI) increases angiotensin II (Ang II) and reactive oxygen species (ROS) that are potent modulators of vascular function. However, the roles of individual ROS and their interaction with Ang II are not clear. Here we tested the hypothesis that IRI modulates renal afferent arteriolar responses to Ang II via increasing superoxide (O2-) or hydrogen peroxide (H2 O2 ). METHODS: Renal afferent arterioles were isolated and perfused from C57BL/6 mice 24 h after IRI or sham surgery. Responses to Ang II or noradrenaline were assessed by measuring arteriolar diameter. Production of H2 O2 and O2- was assessed in afferent arterioles and renal cortex. Activity of SOD and catalase, and mRNA expressions of Ang II receptors were assessed in pre glomerular arterioles and renal cortex. RESULTS: Afferent arterioles from mice after IRI had a reduced maximal contraction to Ang II (-27+/-2 vs. -42+/-1%, P < 0.001), but retained a normal contraction to noradrenaline. Arterioles after IRI had a 38% increase in H2 O2 (P < 0.001) and a 45% decrease in catalase activity (P < 0.01). Contractions were reduced in normal arterioles after incubation with H2 O2 (-22+/-2 vs. -42+/-1%, P < 0.05) similar to the effects of IRI. However, the impaired contractions were normalized by incubation with PEG catalase despite a reduced AT1 R expression. CONCLUSIONS: Renal IRI in mice selectively impairs afferent arteriolar responses to Ang II because of H2 O2 accumulation that is caused by a reduced catalase activity. This could serve to buffer the effect of Ang II after IRI and may be a protective mechanism. PMID- 27362289 TI - Circulating Cytokines Predict the Development of Insulin Resistance in a Prospective Finnish Population Cohort. AB - CONTEXT: Metabolic inflammation contributes to the development of insulin resistance (IR), but the roles of different inflammatory and other cytokines in this process remain unclear. OBJECTIVE: We aimed at analyzing the value of different cytokines in predicting future IR. DESIGN, SETTING, AND PARTICIPANTS: We measured the serum concentrations of 48 cytokines from a nationwide cohort of 2200 Finns (the Cardiovascular Risk in Young Finns Study), and analyzed their role as independent risk factors for predicting the development of IR 4 years later. MAIN OUTCOME MEASURES: We used cross-sectional regression analysis adjusted for known IR risk factors (high age, body mass index, systolic blood pressure, triglycerides, smoking, physical inactivity, and low high-density lipoprotein cholesterol), C-reactive protein and 37 cytokines to find the determinants of continuous baseline IR (defined by homeostatic model assessment). A logistic regression model adjusted for the known risk factors, baseline IR, and 37 cytokines was used to predict the future IR. RESULTS: Several cytokines, often in a sex-dependent manner, remained as independent determinants of current IR. In men, none of the cytokines was an independent predictive risk marker of future IR. In women, in contrast, IL-17 (odds ratio, 1.42 for 1-SD change in ln transformed IL-17) and IL-18 (odds ratio, 1.37) were independently associated with the future IR. IL-17 levels also independently predicted the development of incident future IR (odds ratio, 1.48). CONCLUSIONS: The systemic levels of the T helper 1 cell cytokine IL-18 and the T helper 17 cell cytokine IL-17 thus may have value in predicting future insulin sensitivity in women independently of classical IR risk factors. PMID- 27362290 TI - Notes from the Field: Four Multistate Outbreaks of Human Salmonella Infections Linked to Small Turtle Exposure - United States, 2015. AB - In August 2015, the Food and Drug Administration (FDA) notified CDC of a consumer complaint involving Salmonella Sandiego infection in a child (the index patient), who had acquired a small turtle (shell length <4 inches [<10 cm]) at an Alabama flea market. The subsequent investigation, which included examining data from PulseNet, the national molecular subtyping network for foodborne disease surveillance, identified four multistate Salmonella outbreaks: two involving Salmonella Sandiego and two involving Salmonella Poona. These serotypes have been linked to small turtles in previous outbreaks (1,2). Although selling small turtles as pets in the United States has been banned since 1975 (3), illegal sales still occur at discount stores and flea markets and by street vendors. CDC investigated to determine the extent of the outbreaks and prevent additional infections. PMID- 27362292 TI - Solid-Phase Synthesis of 1,3,4-Thiadiazole Derivatives via Desulfurative Cyclization of Thiosemicarbazide Intermediate Resin. AB - A 1,3,4-thiadiazole library was constructed by solid-phase organic synthesis. The key step of this solid-phase synthesis involves the preparation of polymer-bound 2-amido-5-amino-1,3,4-thiadiazole resin by the cyclization of thiosemicarbazide resin using p-TsCl as the desulfurative agent, followed by the functionalization of the resin by alkylation, acylation, alkylation/acylation, and Suzuki coupling reactions. Both the alkylation and acylation reactions chemoselectively occurred at the 2-amide position of 2-amido-5-amino-1,3,4-thiadiazole resin and the 5 amine position of 2-amido-5-amino-1,3,4-thiadiazole resin, respectively. Finally, these functionalized 1,3,4-thiadiazole resins were treated with trifluoroacetic acid in dichloromethane, affording diverse 1,3,4-thiadiazole analogs in high yields and purities. The 1,3,4-thiadiazole analogs show a different distribution of physicochemical and biological properties compared with our previously constructed 1,3,4-oxadiazole and 1,3,4-thiadiazole libraries in a range of orally available drug properties. PMID- 27362291 TI - Apathy associated with neurocognitive disorders: Recent progress and future directions. AB - INTRODUCTION: Apathy is common in neurocognitive disorders (NCDs) such as Alzheimer's disease and mild cognitive impairment. Although the definition of apathy is inconsistent in the literature, apathy is primarily defined as a loss of motivation and decreased interest in daily activities. METHODS: The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Neuropsychiatric Syndromes Professional Interest Area (NPS PIA) Apathy workgroup reviewed the latest research regarding apathy in NCDs. RESULTS: Progress has recently been made in three areas relevant to apathy: (1) phenomenology, including the use of diagnostic criteria and novel instruments for measurement, (2) neurobiology, including neuroimaging, neuropathological and biomarker correlates, and (3) interventions, including pharmacologic, nonpharmacologic, and noninvasive neuromodulatory approaches. DISCUSSION: Recent progress confirms that apathy has a significant impact on those with major NCD and those with mild NCDs. As such, it is an important target for research and intervention. PMID- 27362293 TI - Negotiation, Mediation and Communication between Cultures: End-of-Life Care for South Asian Immigrants in Canada from the Perspective of Family Caregivers. AB - In the present study, we explored family caregivers' experiences in providing end of-life care for terminally ill South Asian immigrants. We employed qualitative methods and. in-depth interviews were conducted with seven family caregivers living in Nova Scotia, Canada. Interview data were validated, coded and organized for themes. Three major themes identified in the data illustrated (a) how South Asian caregivers experienced clashes between biomedical and ethno-cultural realms of care that led to cultural insensitivity, (b) how family members acted as mediators, and (c) how communication issues that challenged cultural sensitivity were handled. Findings provide directions for culturally sensitive end-of-life care planning. PMID- 27362294 TI - The surface-to-volume ratio: a key parameter in the thermoelectric transport of topological insulator Bi2Se3 nanowires. AB - We systematically investigated the role of topological surface states on thermoelectric transport by varying the surface-to-volume ratio (s/v) of Bi2Se3 nanowires. The thermoelectric coefficients of Bi2Se3 nanowires were significantly influenced by the topological surface states with increasing the s/v. The Seebeck coefficient of Bi2Se3 nanowires decreased with increasing the s/v, while the electrical conductivity increased with increasing the s/v. This implies that the influence of metallic surface states become dominant in thermoelectric transport in thin nanowires, and the s/v is a key parameter which determines the total thermoelectric properties. Our measurements were corroborated by using a two channel Boltzmann transport model. PMID- 27362295 TI - Gene expression analysis of bud and leaf color in tea. AB - Purple shoot tea attributing to the high anthocyanin accumulation is of great interest for its wide health benefits. To better understand potential mechanisms involved in purple buds and leaves formation in tea plants, we performed transcriptome analysis of six green or purple shoot tea individuals from a F1 population using the Illumina sequencing method. Totally 292 million RNA-Seq reads were obtained and assembled into 112,233 unigenes, with an average length of 759 bp and an N50 of 1081 bp. Moreover, totally 2193 unigenes showed significant differences in expression levels between green and purple tea samples, with 1143 up- and 1050 down-regulated in the purple teas. Further real time PCR analysis confirmed RNA-Seq results. Our study identified 28 differentially expressed transcriptional factors and A CsMYB gene was found to be highly similar to AtPAP1 in Arabidopsis. Further analysis of differentially expressed genes involved in anthocyanin biosynthesis and transportation showed that the late biosynthetic genes and genes involved in anthocyanin transportation were largely affected but the early biosynthetic genes were less or none affected. Overall, the identification of a large number of differentially expressed genes offers a global view of the potential mechanisms associated with purple buds and leaves formation, which will facilitate molecular breeding in tea plants. PMID- 27362296 TI - Effect of endophytic Bacillus cereus ERBP inoculation into non-native host: Potentials and challenges for airborne formaldehyde removal. AB - Phytoremediation could be a cost-effective, environmentally friendly approach for the treatment of indoor air. However, some drawbacks still dispute the expediency of phytotechnology. Our objectives were to investigate the competency of plant growth-promoting (PGP) endophytic Bacillus cereus ERBP (endophyte root blue pea), isolated from the root of Clitoria ternatea, to colonize and stabilize within Zamioculcas zamiifolia and Euphorbia milii as non-native hosts without causing any disease or stress symptoms. Moreover, the impact of B. cereus ERBP on the natural shoot endophytic community and for the airborne formaldehyde removal capability of non-native hosts was assessed. Non-native Z. zamiifolia was effectively inoculated with B. cereus ERBP through soil as the most efficient method of endophyte inoculation. Denaturing gradient gel electrophoresis profiling of the shoot endophytic community verified the colonization and stability of B. cereus ERBP within its non-native host during a 20-d fumigation period without interfering with the natural shoot endophytic diversity of Z. zamiifolia. B. cereus ERBP conferred full protection to its non-native host against formaldehyde phytotoxicity and enhanced airborne formaldehyde removal of Z. zamiifolia whereas non-inoculated plants suffered from formaldehyde phytotoxicity because their natural shoot endophytic community was detrimentally affected by formaldehyde. In contrast, B. cereus ERBP inoculation into non-native E. milii deteriorated airborne formaldehyde removal of the non-native host (compared to a non-inoculated one) as B. cereus ERBP interfered with natural shoot endophytic community of E. milii, which caused stress symptoms and stimulated ethylene biosynthesis. Non-native host inoculation with PGP B. cereus ERBP could bear potentials and challenges for airborne formaldehyde removal. PMID- 27362297 TI - Mg deficiency affects leaf Mg remobilization and the proteome in Brassica napus. AB - In order to cope with variable mineral nutrient availability, higher plants have developed numerous strategies including the remobilization of nutrients from source to sink tissues. However, such processes remain relatively unknown for magnesium (Mg), which is the third most important cation in plant tissues. Using Mg depletion of Brassica napus, we have demonstrated that Mg is remobilized from old leaves to young shoot tissues. Moreover, this study showed that Mg depletion induces modification of nutrient uptake, especially Zn and Mn. Finally, comparative proteomic analysis of old leaves (source of Mg) revealed amongst other results that some proteins requiring Mg for their functionality (isocitrate dehydrogenase for example) were up-regulated. Moreover, down-regulation of proteases suggested that mobilization of Mg from old leaves was not associated with senescence. PMID- 27362298 TI - The role of 24-epibrassinolide in the regulation of photosynthetic characteristics and nitrogen metabolism of tomato seedlings under a combined low temperature and weak light stress. AB - In the present study, we aimed to investigate the effects of exogenous 24 epibrassinolide (EBR) on growth, photosynthetic characteristics, chlorophyll fluorescence imaging, and nitrogen metabolism of tomato leaves under low temperature and weak light conditions. The results showed that foliar application of EBR significantly alleviated the inhibition of plant growth, and increased the fresh and dry weights of tomato plants under a combined low temperature and weak light stress. Moreover, EBR also increased the net photosynthetic rate (Pn), light saturation point (LSP), maximal quantum yield of PSII photochemistry (Fv/Fm), actual photochemical efficiency of PSII (FPSII), and photochemical quenching coefficient (qP), but decreased the intercellular CO2 concentration (Ci), light compensation point (LCP) and apparent quantum efficiency (AQE) under low temperature and weak light conditions. In addition, application of EBR to tomato leaves significantly enhanced the activities of nitrate reductase (NR), glutamate dehydrogenase (GDH), glutamine synthetase (GS), and glutamate synthase (GOGAT), but decreased the ammonium content and nitrite reductase (NiR) activity. We observed that EBR remarkably increased the contents of aspartic acid, threonine, serine, glycine, and phenylalanine, while decreasing the accumulation of cysteine, methionine, arginine, and proline under a combined low temperature and light stress. These results suggest that EBR could alleviate the combined stress-induced harmful effects on photosynthesis and nitrogen metabolism, thus leading to improved plant growth. PMID- 27362299 TI - Sugar exchanges in arbuscular mycorrhiza: RiMST5 and RiMST6, two novel Rhizophagus irregularis monosaccharide transporters, are involved in both sugar uptake from the soil and from the plant partner. AB - Arbuscular mycorrhizal (AM) fungi are associated with about 80% of land plants. AM fungi provide inorganic nutrients to plants and in return up to 20% of the plant-fixed CO2 is transferred to the fungal symbionts. Since AM fungi are obligate biotrophs, unraveling how sugars are provided to the fungus partner is a key for understanding the functioning of the symbiosis. In this study, we identified two new monosaccharide transporters from Rhizophagus irregularis (RiMST5 and RiMST6) that we characterized as functional high affinity monosaccharide transporters. RiMST6 was characterized as a glucose specific, high affinity H(+) co-transporter. We provide experimental support for a primary role of both RiMST5 and RiMST6 in sugar uptake directly from the soil. The expression patterns of RiMSTs in response to partial light deprivation and to interaction with different host plants were investigated. Expression of genes coding for RiMSTs was transiently enhanced after 48 h of shading and was unambiguously dependent on the host plant species. These results cast doubt on the 'fair trade' principle under carbon-limiting conditions. Therefore, in light of these findings, the possible mechanisms involved in the modulation between mutualism and parasitism in plant-AM fungus interactions are discussed. PMID- 27362300 TI - A phase II study of clinical activity of SCH 717454 (robatumumab) in patients with relapsed osteosarcoma and Ewing sarcoma. AB - BACKGROUND: Robatumumab (19D12; MK-7454 otherwise known as SCH717454) is a fully human antibody that binds to and inhibits insulin-like growth factor receptor-1 (IGF-1R). This multiinstitutional study (P04720) determined the safety and clinical efficacy of robatumumab in three separate patient groups with resectable osteosarcoma metastases (Group 1), unresectable osteosarcoma metastases (Group 2), and Ewing sarcoma metastases (Group 3). PROCEDURE: Robatumumab infusions were administered every 2 weeks and were well tolerated with minimal toxicity. Centrally reviewed response data were available for 144 patients. RESULTS: Low disease burden was important for osteosarcoma response: three of 31 patients had complete response or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) in resectable patients (Group 1) versus zero of 29 in unresectable patients (Group 2); median overall survival was 20 months in Group 1 versus 8.2 months in Group 2. In centrally reviewed patients with Ewing sarcoma with PET-CT data (N = 84/115), there were six PR, 23 stable disease, and 55 progression of disease by RECIST at 2 months. Patients with Ewing sarcoma had a median overall survival of 6.9 months. However, responding patients with Ewing sarcoma were allowed to continue on treatment after study closure. A minority of patients with metastatic Ewing sarcoma showed clinical responses and have remained healthy after receiving 25-115 doses of robatumumab with remissions of >4 years duration (N = 6). CONCLUSIONS: These findings show that although the IGF 1R remains an attractive treatment target, additional research is needed to identify responders and/or means to achieve durable remissions in order to successfully exploit IGF-1R signal blockade in Ewing sarcoma (clinicaltrials.gov: NCT00617890). PMID- 27362301 TI - Adolescent Narcissism, Aggression, and Prosocial Behavior: The Relevance of Socially Desirable Responding. AB - An important threat to validity in personality research pertains to an individual's motivation to respond in a socially desirable manner on self-report inventories. This issue was examined in this study in the context of narcissism, aggression, and prosocial behavior in a sample of at-risk adolescents. Participants were 161 adolescents (128 males, 29 females, 4 not reported) ranging in age from 16 to 19 years who were attending a residential program for youth who have dropped out of school. Overall, socially desirable response tendencies were negatively correlated with vulnerable narcissism and self-reported aggression. Moreover, low socially desirable responses strengthened the relation between narcissism and self-reported aggression. Socially desirable responding was not associated with self- or peer-reported prosocial behavior and did not moderate the relation between narcissism and prosocial behavior. These findings indicate that the relation between narcissism and aggression is attenuated by concerns with social desirability. However, further work is needed in broader samples of adolescents to more closely examine whether social desirability concerns actually mitigate aggression among some youth or signify underreporting of one's problem behaviors. PMID- 27362302 TI - T follicular Helper Cells in Transplantation: Specialized Helpers Turned Rogue. PMID- 27362303 TI - T Follicular Helper Cells in Transplantation. AB - The recently described T follicular helper (Tfh) cell is required for the production of high affinity antibody. After contact with follicular dendritic cells, Tfh cells move into the germinal centre and provide help to B cells both by direct B cell-T cell interaction and production of IL-21. This drives proliferation, differentiation, and affinity maturation of the B cells to produce plasma cells capable of secreting high-affinity antibody. Circulating Tfh cells are produced by movement of Tfh cells from lymph nodes after dendritic cell contact. A reduction of Tfh cell-associated molecules is linked with increased expression of other chemokine receptors to form Th1-, Th2-, and Th17-like Tfh cells. These circulating Tfh cells are able to help B cells in vitro and to move into target tissues to support antibody production. Alloantibody production is dependent on T-cell help via the indirect pathway. Antibody-mediated rejection is therefore dependent on Tfh cells. Animal data suggest that Tfh cells and B cells migrate to the allograft and are involved in alloantibody production within a tertiary lymphoid organ. There is some data supporting the same process within human allografts. The requirement for T-cell help provides a potential therapeutic target in the treatment of antibody-mediated rejection. PMID- 27362304 TI - UK National Registry Study of Kidney Donation After Circulatory Death for Pediatric Recipients. AB - BACKGROUND: Donation after circulatory death (DCD) kidney transplantation has acceptable renal allograft survival in adults but there are few data in pediatric recipients. The aim of this study was to determine renal allograft outcomes for pediatric recipients of a DCD kidney. METHODS: Data were collected from the UK Transplant Registry held by National Health Service Blood and Transplant. Kidney transplants performed for pediatric recipients (age, <18 years) in the United Kingdom from 2000 to 2014 were separated into DCD, donation after brain death (DBD), and living donor (LD) transplants, analyzing 3-year patient and renal allograft survival. RESULTS: One thousand seven hundred seventy-two kidney only transplants were analyzed. Twenty-one (1.2%) of these were from DCD donors, 955 (53.9%) from DBD donors, and 796 (44.9%) from LDs. Patient survival is 100% in the DCD group, 98.7% in the DBD group, and 98.9% in the LD group. Three-year renal allograft survival was 95.2% in the DCD group, 87.1% in the DBD group, and 92.9% in the LD group. There was no significant difference in 3-year renal allograft survival between the DCD and DBD groups (P = 0.42) or DCD and LD groups (P = 0.84). For DCD, the primary nonfunction rate was 5% and delayed graft function was 25%. CONCLUSIONS: Children receiving a DCD kidney transplant have good renal allograft survival at 3-year follow-up, comparable to those receiving a kidney from a DBD donor or a LD. This limited evidence encourages the use of selected DCD kidneys in pediatric transplantation, and DCD allocation algorithms may need to be reviewed in view of this. PMID- 27362305 TI - The Authors' Reply. PMID- 27362306 TI - Associations Between Posttransplantation Diabetes Mellitus and Renal Graft Survival. AB - BACKGROUND: Previous reports indicate that posttransplantation diabetes mellitus (PTDM) is associated with overall renal graft loss, but not death-censored graft loss. METHODS: In this single-center retrospective cohort study of 2749 adult Norwegian renal transplant recipients, transplanted between 1999 and 2011, we estimated overall and death-censored renal graft loss hazard ratios in patients diagnosed with PTDM, impaired glucose tolerance and diabetes before transplantation, using multivariable Cox proportional hazard regression analysis. RESULTS: A total of 893 renal grafts were lost during the study period, either due to recipient death (n = 540) or death-censored graft loss (n = 353).When the observational time started at time of transplantation, diabetes before transplantation was associated with both overall and death-censored graft loss. Pretransplantation diabetes was also associated with a steeper decline in renal graft function, a higher risk of acute rejections and more renal grafts lost due to acute rejection.In patients with a functional renal graft 1 year after transplantation, PTDM was associated with overall graft loss (hazard ratio, 1.46; 95% confidence interval, 1.13-1.88; P < 0.001), but not death-censored graft loss (hazard ratio, 1.25; 95% confidence interval, 0.80-1.96; P = 0.33). We found no significant associations between PTDM and change in renal function during the first 5 years or acute rejection risk during the first year after renal transplantation.Impaired glucose tolerance was not associated with either overall or death-censored graft loss. CONCLUSIONS: The present study confirms previous findings of an increased risk of overall but not death-censored renal graft loss in renal transplant recipients with PTDM. Longstanding diabetes might increase the risk of acute rejections. PMID- 27362307 TI - Preemptive CD20+ B cell Depletion Attenuates Cardiac Allograft Vasculopathy in CD154-Treated Monkeys. AB - BACKGROUND: Anti-CD154 monotherapy is associated with antidonor allo-antibody (Ab) elaboration, cardiac allograft vasculopathy (CAV), and allograft failure in preclinical primate cell and organ transplant models. In the context of calcineurin inhibitors (CNI), these pathogenic phenomena are delayed by preemptive "induction" B cell depletion. METHODS: alphaCD154 (IDEC-131)-treated cynomolgus monkey heart allograft recipients were given peritransplant rituximab (alphaCD20) alone or with rabbit antihuman thymocyte globulin. RESULTS: Relative to previously reported reference groups, alphaCD20 significantly prolonged survival, delayed Ab detection, and attenuated CAV within 3 months in alphaCD154 treated recipients (alphaCD154 + alphaCD20 graft median survival time > 90 days, n = 7, vs 28 days for alphaCD154 alone (IDEC-131), n = 21; P = 0.05). Addition of rabbit antihuman thymocyte globulin to alphaCD154 (n = 6) or alphaCD154 + alphaCD20 (n = 10) improved graft protection from graft rejection and failure during treatment but was associated with significant morbidity in 8 of 16 recipients (6 infections, 2 drug-related complications). In alphaCD20-treated animals, detection of antidonor Ab and relatively severe CAV were anticipated by appearance of CD20 cells (>1% of lymphocytes) in peripheral blood and were associated with low alphaCD154 trough levels (below 100 MUg/mL). CONCLUSIONS: These observations support the hypothesis that efficient preemptive "induction" CD20 B cell depletion consistently modulates pathogenic alloimmunity and attenuates CAV in this translational model, extending our prior findings with calcineurin inhibitors to the context of CD154 blockade. PMID- 27362309 TI - The Author's Reply. PMID- 27362310 TI - Isolated Human Perfused Lung Models to Study Ex Vivo Lung Optimization. PMID- 27362308 TI - Tracing Donor-MHC Class II Reactive B cells in Mouse Cardiac Transplantation: Delayed CTLA4-Ig Treatment Prevents Memory Alloreactive B-Cell Generation. AB - BACKGROUND: The dual role of B cells as drivers and suppressors of the immune responses have underscored the need to trace the fate of B cells recognizing donor major histocompatibility complex class I and class II after allograft transplantation. METHODS: In this study, we used donor class II tetramers to trace the fate of I-E-specific B cells after immunization with BALB/c spleen cells or cardiac transplantation, in naive or sensitized C57BL/6 recipients. We combined this approach with genetic lineage tracing of memory B cells in activation-induced cytidine deaminase regulated Cre transgenic mice crossed to the ROSA26-enhanced yellow fluorescent protein reporter mice to track endogenous I-E-specific memory B cell generation. RESULTS: Immunization with BALB/c splenocytes or heart transplantation induced an expansion and differentiation of I-E-specific B cells into germinal center B cells, whereas BALB/c heart transplantation into sensitized recipients induced the preferential differentiation into antibody-secreting cells. A 10.8-fold increase in the frequency of I-E-specific memory B cells was observed by day 42 postimmunization. Treatment with CTLA4-Ig starting on day 0 or day 7 postimmunization abrogated I-E specific memory B cell generation and sensitized humoral responses, but not if treatment commenced on day 14. CONCLUSIONS: The majority of donor-specific memory B cells are generated between days 7 and 14 postimmunization, thus revealing a flexible timeframe whereby delayed CTLA4-Ig administration can inhibit sensitization and the generation of memory graft-reactive B cells. PMID- 27362311 TI - Strategic Use of Epitope Matching to Improve Outcomes. AB - Understanding the events leading to allorecognition and the subsequent effector pathways engaged is key for the development of strategies to prolong graft survival. Optimizing patient outcomes will require 2 major advancements: (1) minimizing premature death with a functioning graft in the patients with stable graft function, and (2) maximizing graft survival by avoiding the aforementioned allorecognition. This necessitates personalized immunosuppression to avoid known metabolic side effects, risk for infection, and malignancy, while holding the alloimmune system in check. Since the beginning of transplant a key strategy to achieve this goal is to minimize HLA mismatching between donor and recipient. What has not evolved is any refinement in our evaluation of HLA relatedness between donor and recipient when HLA mismatch exists. Donor-recipient HLA mismatch at the amino acid level can now be determined. These mismatches serve as potential epitopes for de novo donor specific antibody development and correlate with late rejection and graft loss. It is in this context that HLA epitope analysis is considered as a strategy to permit safe immunosuppression minimization to improve patient outcomes through: (1) improved allocation schemes that favor donor-recipient pairs with a low HLA epitope mismatch load (especially at the class II loci) or avoiding specific epitope mismatches known to be highly immunogenic and (2) immunosuppressive minimization in patients with low epitope mismatch loads or without highly immunogenic epitope mismatches. PMID- 27362312 TI - Effect of Induction Therapy on Graft Survival in Primary Pediatric Heart Transplantation: A Propensity Score Analysis of the UNOS Database. AB - BACKGROUND: The use of induction therapy in pediatric heart transplantation has increased. The aim of this study was to investigate the effects of induction therapy on graft survival. METHODS: The United Network for Organ Sharing database was queried for isolated pediatric heart transplants from January 1, 1994, to December 31, 2013. Propensity scores for induction treatment were calculated by estimating probability of induction using a logistic regression model. Transplants were then matched between induction treatment groups based on the propensity score, reducing potential biases. Using only propensity score matched transplants, the effect of induction therapy on graft survival was investigated using Cox-proportional hazards. Subgroup analyses were performed based on age, race, recipient cardiac diagnosis, HLA, and recipient panel-reactive antibody (PRA). RESULTS: Of 4565 pediatric primary heart transplants from 1994 to 2013, 3741 had complete data for the propensity score calculation. There were 2792 transplants successfully matched (induction, n = 1396; no induction, n = 1396). There were no significant differences in transplant and pretransplant covariates between induction and no induction groups. In the Cox-proportional hazards model, the use of induction of was not associated with graft loss (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.75-1.01; P = 0.07). In subgroup analyses, induction therapy may be associated with improved survival in patients with PRA greater than 50% (HR, 0.57; 95% CI, 0.34-0.97) and congenital heart disease (HR, 0.78; 95% CI, 0.64-0.96). CONCLUSIONS: Induction therapy is not associated with improved graft survival in primary pediatric heart transplantation. However, in pediatric heart transplant recipients with PRA greater than 50% or congenital heart disease, induction therapy is associated with improved survival. PMID- 27362314 TI - Molecular and Functional Noninvasive Immune Monitoring in the ESCAPE Study for Prediction of Subclinical Renal Allograft Rejection. AB - BACKGROUND: Subclinical acute rejection (sc-AR) is a main cause for functional decline and kidney graft loss and may only be assessed through surveillance biopsies. METHODS: The predictive capacity of 2 novel noninvasive blood biomarkers, the transcriptional kidney Solid Organ Response Test (kSORT), and the IFN-gamma enzyme-linked immunosorbent spot assay (ELISPOT) assay were assessed in the Evaluation of Sub-Clinical Acute rejection PrEdiction (ESCAPE) Study in 75 consecutive kidney transplants who received 6-month protocol biopsies. Both assays were run individually and in combination to optimize the use of these techniques to predict sc-AR risk. RESULTS: Subclinical acute rejection was observed in 22 (29.3%) patients (17 T cell-mediated subclinical rejection [sc TCMR], 5 antibody-mediated subclinical rejection [sc-ABMR]), whereas 53 (70.7%) showed a noninjured, preserved (stable [STA]) parenchyma. High-risk (HR), low risk, and indeterminate-risk kSORT scores were observed in 15 (20%), 50 (66.7%), and 10 (13.3%) patients, respectively. The ELISPOT assay was positive in 31 (41%) and negative in 44 (58.7%) patients. The kSORT assay showed high accuracy predicting sc-AR (specificity, 98%; positive predictive value 93%) (all sc-ABMR and 58% sc-TCMR showed HR-kSORT), whereas the ELISPOT showed high precision ruling out sc-TCMR (specificity = 70%, negative predictive value = 92.5%), but could not predict sc-ABMR, unlike kSORT. The predictive probabilities for sc-AR, sc-TCMR, and sc-ABMR were significantly higher when combining both biomarkers (area under the curve > 0.85, P < 0.001) and independently predicted the risk of 6-month sc-AR in a multivariate regression analysis. CONCLUSIONS: Combining a molecular and immune cell functional assay may help to identify HR patients for sc-AR, distinguishing between different driving alloimmune effector mechanisms. PMID- 27362313 TI - mTOR Inhibition Suppresses Posttransplant Alloantibody Production Through Direct Inhibition of Alloprimed B Cells and Sparing of CD8+ Antibody-Suppressing T cells. AB - BACKGROUND: De novo alloantibodies (donor-specific antibody) contribute to antibody-mediated rejection and poor long-term graft survival. Because the development of donor-specific antibody is associated with early graft loss of cell transplants and reduced long-term survival of solid organ transplants, we hypothesized that conventional immunosuppressives, calcineurin inhibitors (CNi), and mammalian target of rapamycin inhibitors (mTORi), may not be as effective for suppression of humoral alloimmunity as for cell-mediated immunity. METHODS: Wild type or CD8-depleted mice were transplanted with allogeneic hepatocytes. Recipients were treated with mTORi and/or CNi and serially monitored for alloantibody and graft survival. The direct effect of mTORi and CNi on alloprimed B cell function was investigated in Rag1 mice adoptively transferred with alloprimed IgG1 B cells. The efficacy of mTORi and/or CNi to suppress CD8 mediated cytotoxicity of IgG1 B cells was evaluated in in vitro and in vivo cytotoxicity assays. RESULTS: Mammalian target of rapamycin inhibitors, but not CNi, reduced alloantibody production in transplant recipients, directly suppressed alloantibody production by alloprimed IgG1 B cells and delayed graft rejection in both low and high alloantibody producers. Combination treatment with mTORi and CNi resulted in loss of the inhibitory effect observed for mTORi monotherapy in part due to CNi suppression of CD8 T cells which downregulate alloantibody production (CD8 TAb-supp cells). CONCLUSIONS: Our data support that mTORi is a potent inhibitor of humoral immunity through suppression of alloprimed B cells and preservation of CD8 TAb-supp cells. In contrast, alloantibody is readily detected in CNi-treated recipients because CNi does not suppress alloprimed B cells and interferes with downregulatory CD8 TAb-supp cells. PMID- 27362315 TI - Human Cytomegalovirus-Encoded Receptor US28 Is Expressed in Renal Allografts and Facilitates Viral Spreading In Vitro. AB - BACKGROUND: Renal transplantation is the preferred treatment for patients with end-stage renal disease. Human cytomegalovirus (HCMV) activation is associated with decreased renal graft function and survival. Human cytomegalovirus encodes several immune modulatory proteins, including the G protein-coupled receptor US28, which scavenges human chemokines and modulates intracellular signaling. METHODS: Our aim was to identify the expression and localization of US28 in renal allograft biopsies by immunohistochemistry and determine its role in viral spreading in vitro. RESULTS: Immunohistochemistry revealed US28 in 31 of 34 renal transplant biopsies from HCMV-seropositive donors. Expression was independent of HCMV viremia or IgG serostatus. US28 was predominantly expressed in the cytoplasm of vascular smooth muscle cells (VSMCs) and tubular epithelial cells, with a median positivity of 20% and 40%, respectively. Also, US28-positive cells were present within arterial neointima. In contrast to US28, HCMV-encoded immediate early antigen was detected in less than 5% of VSMCs, tubular epithelial cells, interstitial endothelium, interstitial inflammatory infiltrates, and glomerular cells.Primary VSMCs were infected with green fluorescent protein-tagged wild type or US28-deficient HCMV. The viral spreading of US28-deficient HCMV, via culture medium or cell-to-cell transmission, was significantly impeded as shown by green fluorescent protein (ie, infected) cell quantification and quantitative real-time polymerase chain reaction. Additionally, the number and size of foci was smaller. CONCLUSIONS: In summary, HCMV-encoded US28 was detected in renal allografts from HCMV-positive donors independent of viremia and serostatus. Also, US28 facilitates HCMV spreading in VSMCs in vitro. Because the vasculature is affected in chronic renal transplant dysfunction, US28 may provide a potential target for therapeutic intervention. PMID- 27362316 TI - Higher Bilirubin Levels of Healthy Living Liver Donors Are Associated With Lower Posttransplant Hepatocellular Carcinoma Recurrence. AB - BACKGROUND: Serum bilirubin level, which may reflect the host defense against increased oxidative stress, is inversely associated with the risk of cancer development. In liver transplantation, the intrinsic bilirubin metabolism of donor liver is subsequently translated into recipient. Thus, we hypothesized that liver transplantation conducted with living donors with higher serum bilirubin reduces hepatocellular carcinoma (HCC) recurrence. METHODS: Two hundred fifty recipients who underwent liver transplantation for treating HCC within the Milan criteria were included in the study. The association between donor preoperative total bilirubin concentration and the risk of HCC recurrence was analyzed using the Fine and Gray regression model with posttransplant death as a competing risk event with adjustment for tumor biology including alpha-fetoprotein, histological differentiation, and microvascular invasion. RESULTS: All donors were confirmed to have no underlying hepatobiliary diseases or hematological disorders. Donor preoperative total bilirubin concentration was 0.7 mg/dL in median and ranged from 0.2 to 2.7 mg/dL. Thirty-five (14.0%) recipients developed HCC recurrence. Multivariable analysis demonstrated that donor preoperative total bilirubin concentration was inversely associated with the recurrence risk (hazard ratio, 0.22; 95% confidence interval, 0.07-0.72; P = 0.013). The highest (>=1.0 mg/dL) versus lowest (<=0.6 mg/dL) tertile of donor preoperative total bilirubin showed a significant reduction of the recurrence risk (hazard ratio, 0.28; 95% confidence interval, 0.11-0.70; P = 0.006). CONCLUSIONS: Hepatocellular carcinoma recurrence risk decreases in relation to the increase in total serum bilirubin level of healthy living donors without underlying hepatobiliary or hematological disorders. Further validation of bilirubin as a potent anticancer substance against HCC is warranted. PMID- 27362317 TI - Analysis of Factors Associated With Biliary Complications in Children After Liver Transplantation. AB - BACKGROUND: Biliary complications (BCs) remain an important cause of morbidity after pediatric liver transplantation. Technical factors have already been implicated in the development of BCs. Previous reports have associated the use of partial grafts, particularly living donor grafts, with a higher incidence of BCs. Our aim is to study the factors associated with the development of BCs in a large cohort of pediatric liver transplant recipients. METHODS: Retrospective cohort study of 670 children (<18 years of age) who underwent a primary liver transplant between March 2000 and January 2015. Patients who did and did not develop BCs were compared with identify associated factors. Univariate and multivariate analyses were performed. RESULTS: A total of 115 patients (17.2%) developed BCs (83 strictures and 44 leaks). Of the study participants, 594 had living donor liver transplants. Multiple arterial anastomoses was a protective factor for BCs, and a ductoplasty was a risk factor. Living donor grafts and multiple biliary anastomoses were more frequently associated with leaks. Patients with BCs had a higher reoperation rate and longer hospital stays. There was no difference in patient or graft survival. CONCLUSIONS: Technical factors play a major role in the development of BCs, particularly leaks. Strictures are more frequently associated with an inadequate arterial supply to the bile duct, and multiple arterial anastomoses may protect children from this complication. The use of partial grafts was not an independent factor for BCs in high-volume centers that are experienced with this technique. PMID- 27362318 TI - Preventing Memory B Cell Formation: A Story of Mice and Men? PMID- 27362319 TI - Engineering P450 Peroxygenase to Catalyze Highly Enantioselective Epoxidation of cis-beta-Methylstyrenes. AB - P450 119 peroxygenase and its site-directed mutants are discovered to catalyze the enantioselective epoxidation of methyl-substituted styrenes. Two new site directed P450 119 mutants, namely T213Y and T213M, which were designed to improve the enantioselectivity and activity for the epoxidation of styrene and its methyl substituted derivatives, were studied. The T213M mutant is found to be the first engineered P450 peroxygenase that shows highly enantioselective epoxidation of cis-beta-methylstyrenes, with up to 91 % ee. Molecular modeling studies provide insights into the different catalytic activity of the T213M mutant and the T213Y mutant in the epoxidation of cis-beta-methylstyrene. The results of the calculations also contribute to a better understanding of the substrate specificity and configuration control for the regio- and stereoselective peroxygenation catalyzed by the T213M mutant. PMID- 27362320 TI - Angioedema associated with nonsteroidal anti-inflammatory drugs. AB - PURPOSE OF REVIEW: The review critically assesses the different phenotypes of angioedemas associated with NSAIDs. Angioedemas exacerbated or induced by NSAIDs have high morbidity and, when they affect the larynx, can lead to death by asphyxiation. RECENT FINDINGS: Angioedema can present as a manifestation of a syndrome such as anaphylaxis or it can be a separate entity, which comprises different forms that can be diagnosed based on specific criteria. NSAIDs are the drugs most used worldwide and they are also one of the leading causes of angioedema. SUMMARY: The manuscript addresses the pathophysiology and pharmacogenetics of angioedema, reviews its classification and assesses the diagnosis and management of angioedemas exacerbated and induced by NSAIDs. PMID- 27362321 TI - Relapsing drug-induced hypersensitivity syndrome. AB - PURPOSE OF REVIEW: Drug-induced hypersensitivity syndrome (DIHS) is a serious adverse drug reaction with potential morbidity and mortality. 'Flare up' or relapses in DIHS is a rare but important feature. These relapses may occur within days to several weeks, even after discontinuation of the offending drug. In this article, we review the pathogenesis of DIHS, implication of human herpesvirus 6 reactivation, and describe published case reports of patients with relapsing DIHS. RECENT FINDINGS: Common drugs associated with DIHS include (but are not limited to) antiepileptics such as carbamazepine, phenytoin, and valproic acid; antituberculous drugs; sulfasalazine; allopurinol; and antivirals such as abacavir and nevirapine. Relapses may occur even after cessation of the culprit drug and appropriate management with corticosteroids. Studies have suggested that reactivation of herpesvirus, particularly, human herpesvirus 6, is the main cause of relapses. However, other pathomechanisms have been proposed - case reports have described the importance of drug cosensitization. In such cases, the introduction of a second drug (often an antibiotic) induces the relapse of DIHS. DIHS may also cause multiple drug allergies, where a patient develops sensitisation to other drugs which were previously well tolerated. SUMMARY: Large studies are lacking in this heterogeneous condition. More research is needed to further understand the pathogenesis of drug cosensitization and multiple drug allergies, role of genetics, identification of risk factors, and prevention of relapses in DIHS. PMID- 27362322 TI - Immunopathogenesis and risk factors for allopurinol severe cutaneous adverse reactions. AB - PURPOSE OF REVIEW: The article reviews the immunopathogenesis and risk factors related to allopurinol-induced severe cutaneous adverse reactions (SCARs). RECENT FINDINGS: For years, allopurinol remains one of the leading cause for SCARs worldwide. The pathogenesis of allopurinol-induced SCARs have been discovered in recent years. HLA-B58 : 01 has been found to be strongly associated with allopurinol-SCARs with functional interactions between allopurinol/its metabolite oxypurinol and the T-cell receptor (TCR). However, the genetic strength of HLA B58 : 01 may vary among different ethnic populations. In addition to HLA-B58 : 01, specific T cells with preferential TCR clonotypes, which have no cross reactivity with new xanthine oxidase inhibitors structurally different from allopurinol, are found to play a crucial role for allopurinol-induced SCARs. Furthermore, other nongenetic factors such as renal impairment are also found to be an important factor resulting in allopurinol-induced SCARs of greater severity and poorer prognosis. SUMMARY: There are multiple risk factors for allopurinol induced SCARs, including genetic and nongenetic factors. Activation of specific T cells with preferential TCR and its functional interaction of HLA-B58 : 01 molecule and allopurinol/oxypurinol are involved in the immune mechanism of allopurinol-induced SCAR. Patients with allopurinol-induced SCARs with renal impairment have significantly higher risk of mortality. A structurally different new generation xanthine oxidase inhibitor can provide a safer alternative for patients intolerant to allopurinol. PMID- 27362323 TI - Should patients with pollen fruit syndrome be prescribed an automatic epinephrine injector? AB - PURPOSE OF REVIEW: The review outlines recent insights into our understanding of the complex relationships between pollen and plant food sensitization patterns resulting in the pollen fruit syndrome and the possible risk, upon ingestion, of generalized symptoms rather than localized oropharyngeal reactions. Appreciation of this risk will inform management strategies, which include epinephrine prescription. RECENT FINDINGS: In recent times, the ability to examine molecular components of foods and pollen has allowed further delineation of reactivity patterns. These reveal complex patterns of IgE reactivity and sensitization pathways. More precise definition of these patterns will allow a more accurate analysis of risk of severe food reactions following ingestion. SUMMARY: Despite improvement in diagnostic tests, there remains no completely reliable way to determine whether an individual with pollen fruit syndrome is at risk of a systemic reaction. The decision to prescribe an epinephrine autoinjector must be based on a risk assessment for the individual patient. PMID- 27362325 TI - Comparisons of outcomes with food immunotherapy strategies: efficacy, dosing, adverse effects, and tolerance. AB - PURPOSE OF REVIEW: In the recent decade, oral immunotherapy has been studied in many clinical trials and entails many problems including a low efficacy for real tolerance and a high rate of induced symptoms. The optimal dose for inducing tolerance is unknown. The aim of this review was to clarify the efficacy and safety of oral immunotherapy, focusing on low doses. RECENT FINDINGS: We reviewed articles published in a few years or articles dealing with oral immunotherapy focusing on a low dose. We summarize recent articles on oral immunotherapy and those focusing on low doses. SUMMARY: Although lower doses for oral immunotherapy appear to cause fewer adverse reactions and be more effective than strict elimination, this strategy may be less effective than oral immunotherapy involving larger doses. The optimal dose for inducing tolerance is still unknown. PMID- 27362326 TI - Biotransformation and bioactivation reactions - 2015 literature highlights. AB - Since 1972, Drug Metabolism Reviews has been recognized as one of the principal resources for researchers in pharmacological, pharmaceutical and toxicological fields to keep abreast of advances in drug metabolism science in academia and the pharmaceutical industry. With a distinguished list of authors and editors, the journal covers topics ranging from relatively mature fields, such as cytochrome P450 enzymes, to a variety of emerging fields. We hope to continue this tradition with the current compendium of mini-reviews that highlight novel biotransformation processes that were published during the past year. Each review begins with a summary of the article followed by our comments on novel aspects of the research and their biological implications. This collection of highlights is not intended to be exhaustive, but rather to be illustrative of recent research that provides new insights or approaches that advance the field of drug metabolism. Abbreviations NAPQI N-acetyl-p-benzoquinoneimine ALDH aldehyde dehydrogenase AO aldehyde oxidase AKR aldo-keto reductase CES carboxylesterase CSB cystathionine beta-synthase CSE cystathionine gamma-lyase P450 cytochrome P450 DHPO 2,3-dihydropyridin-4-one ESI electrospray FMO flavin monooxygenase GSH glutathione GSSG glutathione disulfide ICPMS inductively coupled plasma mass spectrometry i.p. intraperitoneal MDR multidrug-resistant NNAL 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanol NNK 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone oaTOF orthogonal acceleration time-of-flight PBK physiologically based kinetic PCP pentachlorophenol SDR short-chain dehydrogenase/reductase SULT sulfotransferase TB tuberculosis. PMID- 27362327 TI - Transcriptional regulation of human and murine short-chain dehydrogenase/reductases (SDRs) - an in silico approach. AB - Numerous physiological functions of the body are controlled by endogenous (e.g. steroids, retinoids, lipid mediators) or exogenous molecules (e.g. drugs, xenobiotics) that bind to transcription factors (TF). The biosynthesis and catabolism of these signaling molecules depend, apart from CYPs, on enzymes belonging to the short-chain dehydrogenase/reductase (SDR) superfamily. Moreover, the contribution of SDRs to the metabolism of therapeutic drugs and xenobiotics is increasingly recognized. However, only scarce information exists regarding the transcriptional regulation of most SDR proteins. This work aims to illustrate the role of nuclear receptors (NR) and TF related to oxidative stress, inflammation, hypoxia, and xenobiotics in the regulation of selected human and murine SDRs that play crucial roles in steroid, retinoid, eicosanoid, fatty acid, and xenobiotic metabolism. These include, for example, 17beta-hydroxysteroid dehydrogenases, retinol dehydrogenases, and carbonyl reductases. Because existing experimental data are limited, an in silico analysis (TRANSFAC((r)) Professional database) of the 5'-upstream sequences for putative response elements was performed. Experimental and in silico data suggest that pharmaceutical, environmental, or dietary NR ligands may alter SDR-mediated retinoid, steroid, and xenobiotic metabolism, likely affecting basic cellular events like energy expenditure, cell proliferation/differentiation, or aging processes. Also, some SDRs are possibly induced by their own substrates. Further experimental work is urgently needed to fully understand the NR-mediated transcriptional regulation of SDRs. This is essential for deducing their possible involvement in drug side effects and will help to identify new substrates and further physiological functions of these SDRs. PMID- 27362324 TI - Biologic therapy in the management of asthma. AB - PURPOSE OF REVIEW: Current asthma management relies on inhaled corticosteroids, but some asthma is not well controlled with inhaled steroids alone or in combination with long-acting bronchodilators or leukotriene pathway inhibitors. The field of biologic therapy has grown dramatically in the past two decades, with current availability of three molecules, with two distinct and highly selective approaches to interfering with the allergic and eosinophilic airway inflammation common to most asthma. This review summarizes current and future options for incorporating biologic therapy into the overall management of asthma. RECENT FINDINGS: Two new biologic agents have been recently introduced in the United States market, supported by well controlled, randomized clinical trials. These trials have provided insight into the types of patients who are most likely to benefit from these novel agents. SUMMARY: In asthma patients with frequent exacerbations, the addition of a biologic agent targeting the interleukin-5 pathway, or immunoglobulin E, can significantly reduce exacerbations and improve asthma control. The clinical predictors of utility of specific agents overlap with one another, highlighting the importance of clinical judgment in the overall management of this complex disorder. PMID- 27362328 TI - Direct Evaluation of the Molar Absorption Coefficient of Hydrated Electron by the Isosbestic Point Method. AB - The knowledge of the absorption spectrum of hydrated electron is of importance in numerous pulse radiolysis studies because it is often used for dosimetry or for second-order rate constant determination. We present a direct method for the evaluation of the molar absorption coefficient of the hydrated electron. It is based on the wavelength measurement of isosbestic points during the reaction of e(-)aq with the methylviologen MV(2+) cations which leads to the formation of MV(+*). The molar absorption coefficient of hydrated electron is obtained using the value of the molar absorption coefficient of MV(+*) at the isosbestic point at 600 nm, i.e., epsilon600nm,(MV(+*)) = 13500 +/- 300 L mol(-1) cm(-1). Therefore, at the maximum of the absorption spectrum of e(-)aq at 715 nm, the value is epsilon715nm,(e(-)aq) = 19700 +/- 400 L mol(-1) cm(-1). The absorption spectrum of the hydrated electron has been re-evaluated and completed from 260 to 850 nm. PMID- 27362331 TI - Does the get up and go test improve predictive accuracy of the Triage Risk Screening Tool or Rowland questionnaire in older patients admitted to the emergency department? AB - OBJECTIVES: To assess the diagnostic characteristics of the get up and go test (GUGT) as a stand-alone test and in combination with the Flemish Triage Risk Screening Tool (fTRST) and Rowland questionnaire. One aim was to determine whether the diagnostic accuracy of these instruments could be improved for predicting unplanned emergency department (ED) readmission following ED discharge. METHODS: We carried out a prospective cohort study at the ED of the University Hospitals Leuven, Belgium. All patients aged at least 75 years (n=380) completed fTRST, Rowland, and GUGT testing at the index ED admission. Diagnostic characteristics for unplanned ED readmission were determined for hospitalized and discharged patients 1 and 3 months after the index ED visit. RESULTS: In both hospitalized and discharged patients, fTRST and Rowland (cut-off >=2) had good to excellent sensitivity and negative predictive value (NPV) but low to moderate specificity and accuracy; GUGT had low sensitivity and good to excellent NPV and specificity. The combined fTRST/GUGT or Rowland/GUGT had moderate to excellent NPV (56.3-94.3%). The combined fTRST (cut-off >=2)/GUGT had low sensitivity and moderate to excellent specificity. Sensitivity of the combined Rowland (cut-off >=4)/GUGT was good at the 1-month follow-up and moderate at the 3-month follow-up for hospitalized patients; it was low for discharged patients. Specificity was low for hospitalized patients and good for discharged patients. CONCLUSION: Neither the objective measure of mobility (GUGT) nor the combined fTRST/GUGT or Rowland/GUGT improved the results. Our analysis shows that the predictive accuracy of the stand-alone, self-reported screening instruments fTRST and Rowland (cut-off=2) is still good. This study also confirmed their previously known limitations. PMID- 27362329 TI - Probing Nucleosome Stability with a DNA Origami Nanocaliper. AB - The organization of eukaryotic DNA into nucleosomes and chromatin undergoes dynamic structural changes to regulate genome processing, including transcription and DNA repair. Critical chromatin rearrangements occur over a wide range of distances, including the mesoscopic length scale of tens of nanometers. However, there is a lack of methodologies that probe changes over this mesoscopic length scale within chromatin. We have designed, constructed, and implemented a DNA based nanocaliper that probes this mesoscopic length scale. We developed an approach of integrating nucleosomes into our nanocaliper at two attachment points with over 50% efficiency. Here, we focused on attaching the two DNA ends of the nucleosome to the ends of the two nanocaliper arms, so the hinge angle is a readout of the nucleosome end-to-end distance. We demonstrate that nucleosomes integrated with 6, 26, and 51 bp linker DNA are partially unwrapped by the nanocaliper by an amount consistent with previously observed structural transitions. In contrast, the nucleosomes integrated with the longer 75 bp linker DNA remain fully wrapped. We found that the nanocaliper angle is a sensitive measure of nucleosome disassembly and can read out transcription factor (TF) binding to its target site within the nucleosome. Interestingly, the nanocaliper not only detects TF binding but also significantly increases the probability of TF occupancy at its site by partially unwrapping the nucleosome. These studies demonstrate the feasibility of using DNA nanotechnology to both detect and manipulate nucleosome structure, which provides a foundation of future mesoscale studies of nucleosome and chromatin structural dynamics. PMID- 27362332 TI - Time-Resolved Measurements of Photocarrier Dynamics in TiS3 Nanoribbons. AB - We report synthesis and time-resolved transient absorption measurements of TiS3 nanoribbons. TiS3 nanoribbons were fabricated by direct reaction of titanium and sulfur. Dynamics of the photocarriers in these samples were studied by transient absorption measurements. It was found that following ultrafast injection of nonequilibrium and hot photocarriers, the thermalization, energy relaxation, and exciton formation all occur on a subpicosecond time scale. Several key parameters describing the dynamical properties of photocarriers, including their recombination lifetime, diffusion coefficient, mobility, and diffusion length, were deduced. PMID- 27362335 TI - Ten years of Nature Protocols. PMID- 27362334 TI - Cancer diagnosis disclosure preferences of family caregivers of cancer patients in Egypt. AB - OBJECTIVE: Family caregivers (FCs) of cancer patients are frequently seen as a barrier to honest communication with patients in Egypt. This study was conducted to investigate the attitude of FCs of cancer patients toward cancer diagnosis disclosure (CDD) and its determinants. METHODS: A structured interview was used to assess the preferences of 288 FCs regarding CDD. RESULTS: According to the FCs, 85% of patients were aware of their diagnosis. The majority (81%) of FCs preferred CDD to patients. In case they developed cancer, 92% of FCs wanted to know their diagnosis and 88% wanted to inform their families. In a univariate analysis, factors associated with FCs' negative attitude toward CDD to patients were as follows: patient's lower level of education (P = .001), patient's rural residence (P < .001), hematological malignancies (P < .001), FC's belief that the patient is unaware of diagnosis (P < .001), FC's unwillingness to know his/her own cancer diagnosis (P < .001), and FC's unwillingness to inform his/her family about his/her cancer diagnosis (P < .001). Only 2 factors predicted independently the negative attitude of FCs toward CDD, the FC's belief that the patient is unaware of diagnosis (P < .001), and the FC's unwillingness to know his/her own cancer diagnosis (P = .049). CONCLUSIONS: The results suggest that the majority of FCs of Egyptian cancer patients prefer CDD to patients. The finding that the vast majority of FCs of aware patients preferred CDD suggests that the reaction of Egyptian patients to CDD is acceptable by FCs. Family caregivers with a negative attitude toward CDD may be reflecting their own fears. PMID- 27362330 TI - Potential new complication in drug therapy development for amyotrophic lateral sclerosis. AB - INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration in the brain and spinal cord. Treatment development for ALS is complicated by complex underlying disease factors. Areas covered: Numerous tested drug compounds have shown no benefits in ALS patients, although effective in animal models. Discrepant results of pre clinical animal studies and clinical trials for ALS have primarily been attributed to limitations of ALS animal models for drug-screening studies and methodological inconsistencies in human trials. Current status of pre-clinical and clinical trials in ALS is summarized. Specific blood-CNS barrier damage in ALS patients, as a novel potential reason for the clinical failures in drug therapies, is discussed. Expert commentary: Pathological perivascular collagen IV accumulation, one unique characteristic of barrier damage in ALS patients, could be hindering transport of therapeutics to the CNS. Restoration of B-CNS-B integrity would foster delivery of therapeutics to the CNS. PMID- 27362333 TI - Endothelial notch signaling is essential to prevent hepatic vascular malformations in mice. AB - Liver vasculature is crucial for adequate hepatic functions. Global deletion of Notch signaling in mice results in liver vascular pathologies. However, whether Notch in endothelium is essential for hepatic vascular structure and function remains unknown. To uncover the function of endothelial Notch in the liver, we deleted Rbpj, a transcription factor mediating all canonical Notch signaling, or Notch1 from the endothelium of postnatal mice. We investigated the hepatic vascular defects in these mutants. The liver was severely affected within 2 weeks of endothelial deletion of Rbpj from birth. Two-week old mutant mice had enlarged vessels on the liver surface, abnormal vascular architecture, and dilated sinusoids. Vascular casting and fluorosphere passage experiments indicated the presence of porto-systemic shunts. These mutant mice presented with severely necrotic liver parenchyma and significantly larger hypoxic areas, likely resulting from vascular shunts. We also found elevated levels of VEGF receptor 3 together with reduced levels of ephrin-B2, suggesting a possible contribution of these factors to the generation of hepatic vascular abnormalities. Deletion of Rbpj from the adult endothelium also led to dilated sinusoids, vascular shunts, and necrosis, albeit milder than that observed in mice with deletion from birth. Similar to deletion of Rbpj, loss of endothelial Notch1 from birth led to similar hepatic vascular malformations within 2 weeks. CONCLUSIONS: Endothelial Notch signaling is essential for the development and maintenance of proper hepatic vascular architecture and function. These findings may elucidate the molecular pathogenesis of hepatic vascular malformation and the safety of therapeutics inhibiting Notch. (Hepatology 2016;64:1302-1316). PMID- 27362336 TI - Solid-phase microextraction to determine micropollutant-macromolecule partition coefficients. AB - Aqueous micropollutants such as estradiol can have a large environmental impact even at low concentrations. Part of understanding this impact involves determining the extent to which the micropollutants interact with macromolecules in water. In environmental samples, relevant macromolecules to which micropollutants bind are referred to as dissolved organic matter, and the most common examples of these in freshwater and coastal seawater are fulvic and humic acids. In living organisms, the most common macromolecules that affect bioavailability of a drug (or toxin) are proteins such as albumin. Using [2, 4, 6, 7 - (3)H]estradiol as an example compound, this protocol uses solid-phase microextraction and scintillation detection as analytical tools to quantify the amount of radiolabeled micropollutant available in solution. The measured free concentration after exposure to various concentrations of macromolecule (dissolved organic matter or protein) or micropollutant is used to determine the partition coefficient in the case of micropollutant-macromolecule interactions. The calibration and preparatory studies take at least 8 d, and the steps to determine the partition coefficient can be completed within 3 d. The protocol could be modified such that nonlabeled compounds are studied; instead of detection of activity by a liquid scintillation counter (LSC), the compounds can be quantified using gas chromatography-mass spectrometry (GC-MS) or liquid chromatography (LC)-MS(/MS). PMID- 27362337 TI - In vivo monitoring of cellular energy metabolism using SoNar, a highly responsive sensor for NAD(+)/NADH redox state. AB - NADH and its oxidized form NAD(+) have a central role in energy metabolism, and their concentrations are often considered to be among the most important readouts of metabolic state. Here, we present a detailed protocol to image and monitor NAD(+)/NADH redox state in living cells and in vivo using a highly responsive, genetically encoded fluorescent sensor known as SoNar (sensor of NAD(H) redox). The chimeric SoNar protein was initially developed by inserting circularly permuted yellow fluorescent protein (cpYFP) into the NADH-binding domain of Rex protein from Thermus aquaticus (T-Rex). It functions by binding to either NAD(+) or NADH, thus inducing protein conformational changes that affect its fluorescent properties. We first describe steps for how to establish SoNar-expressing cells, and then discuss how to use the system to quantify the intracellular redox state. This approach is sensitive, accurate, simple and able to report subtle perturbations of various pathways of energy metabolism in real time. We also detail the application of SoNar to high-throughput chemical screening of candidate compounds targeting cell metabolism in a microplate-reader-based assay, along with in vivo fluorescence imaging of tumor xenografts expressing SoNar in mice. Typically, the approximate time frame for fluorescence imaging of SoNar is 30 min for living cells and 60 min for living mice. For high-throughput chemical screening in a 384-well-plate assay, the whole procedure generally takes no longer than 60 min to assess the effects of 380 compounds on cell metabolism. PMID- 27362338 TI - Single-cell in vivo imaging of adult neural stem cells in the zebrafish telencephalon. AB - Adult neural stem cells (aNSCs) in zebrafish produce mature neurons throughout their entire life span in both the intact and regenerating brain. An understanding of the behavior of aNSCs in their intact niche and during regeneration in vivo should facilitate the identification of the molecular mechanisms controlling regeneration-specific cellular events. A greater understanding of the process in regeneration-competent species may enable regeneration to be achieved in regeneration-incompetent species, including humans. Here we describe a protocol for labeling and repetitive imaging of aNSCs in vivo. We label single aNSCs, allowing nonambiguous re-identification of single cells in repetitive imaging sessions using electroporation of a red-reporter plasmid in Tg(gfap:GFP)mi2001 transgenic fish expressing GFP in aNSCs. We image using two-photon microscopy through the thinned skull of anesthetized and immobilized fish. Our protocol allows imaging every 2 d for a period of up to 1 month. This methodology allowed the visualization of aNSC behavior in vivo in their natural niche, in contrast to previously available technologies, which rely on the imaging of either dissociated cells or tissue slices. We used this protocol to follow the mode of aNSC division, fate changes and cell death in both the intact and injured zebrafish telencephalon. This experimental setup can be widely used, with minimal prior experience, to assess key factors for processes that modulate aNSC behavior. A typical experiment with data analysis takes up to 1.5 months. PMID- 27362339 TI - Delineating potential epileptogenic areas utilizing resting functional magnetic resonance imaging (fMRI) in epilepsy patients. AB - Seizure localization includes neuroimaging like electroencephalogram, and magnetic resonance imaging (MRI) with limited ability to characterize the epileptogenic network. Temporal clustering analysis (TCA) characterizes epileptogenic network congruent with interictal epileptiform discharges by clustering together voxels with transient signals. We generated epileptogenic areas for 12 of 13 epilepsy patients with TCA, congruent with different areas of seizure onset. Resting functional MRI (fMRI) scans are noninvasive, and can be acquired quickly, in patients with different levels of severity and function. Analyzing resting fMRI data using TCA is quick and can complement clinical methods to characterize the epileptogenic network. PMID- 27362340 TI - Old Dogs, New Tricks: Monogenic Autoinflammatory Disease Unleashed. AB - Autoinflammatory diseases are inborn disorders of the innate immune system characterized by episodes of systemic inflammation that are mediated largely by myeloid cells. The field of autoinflammatory diseases has been established since 1999, following the identification of the first genes underlying periodic fever syndromes. This review focuses on developments that have transformed the field in the last two years. We discuss three newly described monogenic autoinflammatory diseases [deficiency of adenosine deaminase 2 (DADA2), a subtype of macrophage activation syndrome (MAS), and stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI)], discuss the possibilities of somatic mosaicism and digenic inheritance, and give an update on new concepts in pathways involved in familial Mediterranean fever (FMF). Finally, the new monogenic autoinflammatory disease haploinsufficiency of A20 (HA20) underscores the placement of monogenic diseases in the firmament of common autoinflammatory phenotypes. The advances in the last two years have shed light on the pathophysiology of several autoinflammatory diseases and have elucidated new pathways that play a role in innate immunity. PMID- 27362341 TI - Defining the Clinical Value of a Genomic Diagnosis in the Era of Next-Generation Sequencing. AB - As with all fields of medicine, the first step toward medical management of genetic disorders is obtaining an accurate diagnosis, which often requires testing at the molecular level. Unfortunately, given the large number of genetic conditions without a specific intervention, only rarely does a genetic diagnosis alter patient management-which raises the question, what is the added value of obtaining a molecular diagnosis? Given the fast-paced advancement of genomic technologies, this is an important question to address in the context of genome scale testing. Here, we address the value of establishing a diagnosis using genome-scale testing and highlight the benefits and drawbacks of such testing. We also review and compare recent major studies implementing genome-scale sequencing methods to identify a molecular diagnosis in cohorts manifesting a broad range of Mendelian monogenic disorders. Finally, we discuss potential future applications of genomic sequencing, such as screening for rare conditions. PMID- 27362342 TI - Advancements in Next-Generation Sequencing. AB - The term next-generation sequencing is almost a decade old, but it remains the colloquial way to describe highly parallel or high-output sequencing methods that produce data at or beyond the genome scale. Since the introduction of these technologies, the number of applications and methods that leverage the power of genome-scale sequencing has increased at an exponential pace. This review highlights recent concepts, technologies, and methods from next-generation sequencing to illustrate the breadth and depth of the applications and research areas that are driving progress in genomics. PMID- 27362343 TI - Identification of specific activities associated with fall-related injuries, active component, U.S. Army, 2011. AB - Although falls continue to be a leading mechanism of serious injuries among military populations, interventions must target activities or hazards that can be controlled or managed. This project aimed to identify activities most frequently associated with Army soldier fall-related injuries to prioritize prevention strategies for this substantial health burden. Narrative data from Army safety, medical evacuation, and casualty reporting systems were reviewed to select incidents meeting inclusion criteria and assign established codes. Nondeployed (n=988) and deployed (n=254) injury rates were not statistically different (2.20 per 1,000 non-deployed person-years [p-yrs], 2.21 per 1,000 deployed p-yrs, respectively). More than 75% of injuries were temporarily disabling fractures, sprains, and strains, primarily to lower extremities. The most frequent activities associated with non-deployed fall injuries were sports (e.g., snowboarding and basketball; 22%), parachuting (20%), walking/marching (19%), and climbing (15%). Ice and snow were the leading hazard (43%). The most common associated activities among deployed soldiers were occupational tasks (53%), walking/patrolling (24%), climbing (23%), and sports (17%). Specific interventions that target the activities and hazards identified in this investigation are suggested as priorities to reduce Army fall-related injuries. PMID- 27362344 TI - Incidence and recent trends in functional gastrointestinal disorders, active component, U.S. Armed Forces, 2005-2014. AB - Functional gastrointestinal disorders (FGIDs) are common chronic conditions with an unknown pathophysiology and etiology. FGIDs elevate healthcare costs and cause substantial burden to public health and the military, including diminished readiness, productivity, and quality of life. This retrospective cohort study of active component U.S. military personnel covered a 10-year surveillance period, 2005-2014. The Defense Medical Surveillance System (DMSS) was the data source. Incident cases were identified and rates were calculated and stratified by important covariates. Trends were described over the surveillance period. Incidence rates among deployed personnel were compared to rates in non-deployed personnel, stratified by age and sex. An increasing trend in functional constipation was observed during 2005-2012. Being female, black, in the Army or Air Force, and younger than 20 years of age or 40 years of age or older was associated with higher incidence rates. Deployment-exposed personnel had incidence rates that were 53% higher than those of non-deployed personnel. Elevated rates in personnel younger than 20 years of age and deployed personnel evoke interest concerning readiness and cost implications for the Military Health System. These subgroups should be examined in future studies. PMID- 27362345 TI - Electronic and magnetic properties of superconducting LnO1-x F x BiS2 (Ln = La, Ce, Pr, and Nd) from first principles. AB - A density functional theory study of the BiS2 superconductors containing rare earths: LnO1-x F x BiS2 (Ln = La, Ce, Pr, and Nd) is presented. We find that CeO0.5F0.5BiS2 has competing ferromagnetic and weak antiferromagnetic tendencies, the first one corresponding to experimental results. We show that PrO0.5F0.5BiS2 has a strong tendency for magnetic order, which can be ferromagnetic or antiferromagnetic depending on subtle differences in 4f orbital occupations. We demonstrate that NdO0.5F0.5BiS2 has a stable magnetic ground state with weak tendency to order. Finally, we show that the change of rare earth does not affect the Fermi surface, and predict that CeOBiS2 should display a pressure induced phase transition to a metallic, if not superconducting, phase under pressure. PMID- 27362346 TI - Differential Survival among Batches of Atlantic Cod (Gadus morhua L.) from Fertilisation through to Post-Metamorphosis. AB - Aquaculture production of cod has decreased from over 20,000 tonnes in 2009 to less than 2,000 tonnes in 2014 and the industry faces many challenges, one of which is high and unpredictably variable mortality rates in the early life stages. Hence, full-cycle farming with hatchery produced juveniles is still considered unprofitable compared to fisheries and on-growing of wild cod. In the present study, potential batch differences in progeny survival of wild-caught, hatchery-spawned Faroe Bank cod (Gadus morhua L.) were investigated at two defined periods during early life history; i) the embryo stage (60 day degrees post fertilisation) and ii) the fry stage (110 days post hatch), post metamorphosis. The fry stage experiment was conducted in three replicates (N = 300 per replicate), and a panel of three polymorphic microsatellite markers was used for parental analysis. Mean survival rate at the embryo stage was 69% (+/- 20% SD). Survival was positively associated with egg diameter (P < 0.01), explaining 90% of the variation in egg survival rates. The data were too scarce to conclude either way concerning a possible correlation between survival rates between the two periods (P < 0.10). Offspring from three batches (from a total of eight) dominated in the fry stage, contributing over 90% of the progeny, and results were consistent over all three replicate tanks. The skewed batch representation observed may be of relevance to the effective management of selective breeding programmes for cod. PMID- 27362347 TI - Using Optimal Land-Use Scenarios to Assess Trade-Offs between Conservation, Development, and Social Values. AB - Development of land resources can contribute to increased economic productivity but can also negatively affect the extent and condition of native vegetation, jeopardize the persistence of native species, reduce water quality, and erode ecosystem services. Spatial planning must therefore balance outcomes for conservation, development, and social goals. One approach to evaluating these trade-offs is scenario planning. In this paper we demonstrate methods for incorporating stakeholder preferences into scenario planning through both defining scenario objectives and evaluating the scenarios that emerge. In this way, we aim to develop spatial plans capable of informing actual land-use decisions. We used a novel approach to scenario planning that couples optimal land-use design and social evaluation of environmental outcomes. Four land-use scenarios combined differences in total clearing levels (10% and 20%) in our study region, the Daly Catchment Australia, with the presence or absence of spatial precincts to concentrate irrigated agriculture. We used the systematic conservation planning tool Marxan with Zones to optimally plan for multiple land uses that met objectives for both conservation and development. We assessed the performance of the scenarios in terms of the number of objectives met and the degree to which existing land-use policies were compromised (e.g., whether clearing limits in existing guidelines were exceeded or not). We also assessed the land-use scenarios using expected stakeholder satisfaction with changes in the catchment to explore how the scenarios performed against social preferences. There were a small fraction of conservation objectives with high conservation targets (100%) that could not be met due to current land uses; all other conservation and development objectives were met in all scenarios. Most scenarios adhered to the existing clearing guidelines with only marginal exceedances of limits, indicating that the scenario objectives were compatible with existing policy. We found that two key stakeholder groups, agricultural and Indigenous residents, had divergent satisfaction levels with the amount of clearing and agricultural development. Based on the range of benefits and potential adverse impacts of each scenario, we suggest that the 10% clearing scenarios are most aligned with stakeholder preferences and best balance preferences across stakeholder groups. Our approach to scenario planning is applicable generally to exploring the potential conflicts between goals for conservation and development. Our case study is particularly relevant to current discussion about increased agricultural and pastoral development in northern Australia. PMID- 27362348 TI - Prevalence and Correlates of Self-Harm in the German General Population. AB - The study aimed at evaluating the psychometric properties of the German version of the Self- Harm Inventory (SHI) and examining the lifetime prevalence and correlates of self-harm in a representative German population sample (N = 2,507; age mean = 48.79, SD = 18.11; range 14 to 94 years; 55.5% women) using the SHI. All participants answered the German SHI, the short form of the Barratt Impulsiveness Scale (BIS-15), the ultra-brief Patient Health Questionnaire for Depression and Anxiety (PHQ-4), and provided sociodemographic information. The one-factorial structure of the SHI was replicated using a confirmatory factor analysis. Internal consistency coefficients were sufficient and in line with previous studies. Almost half of the sample (49%) acknowledged at least one self harming behavior over the life-span, most frequently indirect forms of self-harm. The rate of participants who engaged in at least one SHI behavior was higher among men than women (51.6% vs. 46.9%, respectively, chi2 = 5.38, p = 0.020). Higher SHI scores were related to younger age, male gender, living alone, more symptoms of anxiety and depression (PHQ-4), higher impulsivity scores (BIS-15), and suffering from obesity grade 2. Women engaged more often in discreet forms of self-harm than men, e.g., preventing wounds from healing, exercising an injury, starving, and abusing laxatives. In terms of other indirect self-harming behaviors, men admitted more often driving recklessly, being promiscuous and losing a job on purpose, while women reported more frequently engaging in emotionally abusive relationships. With respect to direct self-harm, women were more likely to endorse suicide attempts and cutting, while men admitted more often head-banging. The findings suggest that self-harm constitutes a common problem. Future longitudinal studies are required to examine the natural course, sociodemographic and psychopathological risk factors, as well as possible time trends of self-harming behaviors in more depth. PMID- 27362349 TI - Linker flexibility of IVS3-S4 loops modulates voltage-dependent activation of L type Ca2+ channels. AB - Extracellular S3-S4 linkers of domain IV (IVS3-S4) of L-type Ca2+ channels (CaV1) are subject to alternative splicing, resulting into distinct gating profiles serving for diverse physiological roles. However, it has remained elusive what would be the determining factor of IVS3-S4 effects on CaV1 channels. In this study, we systematically compared IVS3-S4 variants from CaV1.1-1.4, and discover that the flexibility of the linker plays a prominent role in gating characteristics. Chimeric analysis and mutagenesis demonstrated that changes in half activation voltage (V1/2) or activation time constant (tau) are positively correlated with the numbers of flexible glycine residues within the linker. Moreover, antibodies that reduce IVS3-S4 flexibility negatively shifted V1/2, emerging as a new category of CaV1 enhancers. In summary, our results suggest that the flexibility or rigidity of IVS3-S4 linker underlies its modulations on CaV1 activation (V1/2 and tau), paving the way to dissect the core mechanisms and to develop innovative perturbations pertaining to voltage-sensing S4 and its vicinities. PMID- 27362350 TI - Acute Activation of Metabolic Syndrome Components in Pediatric Acute Lymphoblastic Leukemia Patients Treated with Dexamethasone. AB - Although dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), it can cause serious metabolic side effects. Because studies regarding the effects of dexamethasone are limited by their small scale, we prospectively studied the direct effects of treating pediatric ALL with dexamethasone administration with respect to activation of components of metabolic syndrome (MetS); in addition, we investigated whether these side effects were correlated with the level of dexamethasone. Fifty pediatric patients (3-16 years of age) with ALL were studied during a 5-day dexamethasone course during the maintenance phase of the Dutch Childhood Oncology Group ALL-10 and ALL 11 protocols. Fasting insulin, glucose, total cholesterol, HDL, LDL, and triglycerides levels were measured at baseline (before the start of dexamethasone; T1) and on the fifth day of treatment (T2). Dexamethasone trough levels were measured at T2. We found that dexamethasone treatment significantly increased the following fasting serum levels (P<0.05): HDL, LDL, total cholesterol, triglycerides, glucose, and insulin. In addition, dexamethasone increased insulin resistance (HOMA-IR>3.4) from 8% to 85% (P<0.01). Dexamethasone treatment also significantly increased the diastolic and systolic blood pressure. Lastly, dexamethasone trough levels (N = 24) were directly correlated with high glucose levels at T2, but not with other parameters. These results indicate that dexamethasone treatment acutely induces three components of the MetS. Together with the weight gain typically associated with dexamethasone treatment, these factors may contribute to the higher prevalence of MetS and cardiovascular risk among survivors of childhood leukemia who received dexamethasone treatment. PMID- 27362351 TI - Empathic accuracy for happiness in the daily lives of older couples: Fluid cognitive performance predicts pattern accuracy among men. AB - Correctly identifying other's emotional states is a central cognitive component of empathy. We examined the role of fluid cognitive performance for empathic accuracy for happiness in the daily lives of 86 older couples (mean relationship length = 45 years; mean age = 75 years) on up to 42 occasions over 7 consecutive days. Men performing better on the Digit Symbol test were more accurate in identifying ups and downs of their partner's happiness. A similar association was not found for women. We discuss the potential role of fluid cognitive performance and other individual, partner, and situation characteristics for empathic accuracy. (PsycINFO Database Record PMID- 27362352 TI - Super Resolution Fluorescence Microscopy and Tracking of Bacterial Flotillin (Reggie) Paralogs Provide Evidence for Defined-Sized Protein Microdomains within the Bacterial Membrane but Absence of Clusters Containing Detergent-Resistant Proteins. AB - Biological membranes have been proposed to contain microdomains of a specific lipid composition, in which distinct groups of proteins are clustered. Flotillin like proteins are conserved between pro-and eukaryotes, play an important function in several eukaryotic and bacterial cells, and define in vertebrates a type of so-called detergent-resistant microdomains. Using STED microscopy, we show that two bacterial flotillins, FloA and FloT, form defined assemblies with an average diameter of 85 to 110 nm in the model bacterium Bacillus subtilis. Interestingly, flotillin microdomains are of similar size in eukaryotic cells. The soluble domains of FloA form higher order oligomers of up to several hundred kDa in vitro, showing that like eukaryotic flotillins, bacterial assemblies are based in part on their ability to self-oligomerize. However, B. subtilis paralogs show significantly different diffusion rates, and consequently do not colocalize into a common microdomain. Dual colour time lapse experiments of flotillins together with other detergent-resistant proteins in bacteria show that proteins colocalize for no longer than a few hundred milliseconds, and do not move together. Our data reveal that the bacterial membrane contains defined-sized protein domains rather than functional microdomains dependent on flotillins. Based on their distinct dynamics, FloA and FloT confer spatially distinguishable activities, but do not serve as molecular scaffolds. PMID- 27362353 TI - Dissecting Virus Infectious Cycles by Cryo-Electron Microscopy. PMID- 27362354 TI - Measuring Quality of Maternal and Newborn Care in Developing Countries Using Demographic and Health Surveys. AB - BACKGROUND: One of the greatest obstacles facing efforts to address quality of care in low and middle income countries is the absence of relevant and reliable data. This article proposes a methodology for creating a single "Quality Index" (QI) representing quality of maternal and neonatal health care based upon data collected as part of the Demographic and Health Survey (DHS) program. METHODS: Using the 2012 Indonesian Demographic and Health Survey dataset, indicators of quality of care were identified based on the recommended guidelines outlined in the WHO Integrated Management of Pregnancy and Childbirth. Two sets of indicators were created; one set only including indicators available in the standard DHS questionnaire and the other including all indicators identified in the Indonesian dataset. For each indicator set composite indices were created using Principal Components Analysis and a modified form of Equal Weighting. These indices were tested for internal coherence and robustness, as well as their comparability with each other. Finally a single QI was chosen to explore the variation in index scores across a number of known equity markers in Indonesia including wealth, urban rural status and geographical region. RESULTS: The process of creating quality indexes from standard DHS data was proven to be feasible, and initial results from Indonesia indicate particular disparities in the quality of care received by the poor as well as those living in outlying regions. CONCLUSIONS: The QI represents an important step forward in efforts to understand, measure and improve quality of MNCH care in developing countries. PMID- 27362355 TI - Increased Risk of Acute Kidney Injury following Pneumococcal Pneumonia: A Nationwide Cohort Study. AB - PURPOSE: Pneumococcal disease leads to renal complications ranging from persistent proteinuria to end-stage renal disease. Studies on the association between pneumococcal pneumonia (PP) and acute kidney injury (AKI) are scant. This study assessed the relationship between PP and risk of AKI. METHODS: This nationwide population-based cohort study examined data from the Taiwan National Health Insurance Research Database for the period 2000-2011. We identified inpatients with newly diagnosed PP according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. In addition, we selected a comparison cohort from inpatient claims without the diagnosis of PP that was randomly frequency-matched with the PP cohort according to age, sex, index year and comorbidities. We analyzed the risks of AKI by using Cox proportional hazards regression models, adjusted for sex, age, and comorbidities. RESULTS: A total of 10,069 patients with PP and 10,069 controls were enrolled in this study. After adjustments for age, sex, and comorbidities, patients with PP had a 1.11-fold risk of developing AKI compared with the comparison cohort. CONCLUSION: This study indicates that AKI risks are higher in patients with PP compared with the comparison cohort. Careful follow-up observation and aggressive treatment are necessary for patients with PP to reduce the risk of AKI. PMID- 27362356 TI - Systematic Review of Willingness to Pay for Health Insurance in Low and Middle Income Countries. AB - OBJECTIVE: Access to healthcare is mostly contingent on out-of-pocket spending (OOPS) by health seekers, particularly in low- and middle-income countries (LMICs). This would require many LMICs to raise enough funds to achieve universal health insurance coverage. But, are individuals or households willing to pay for health insurance, and how much? What factors positively affect WTP for health insurance? We wanted to examine the evidence for this, through a review of the literature. METHODS: We systematically searched databases up to February 2016 and included studies of individual or household WTP for health insurance. Two authors appraised the identified studies. We estimated the WTP as a percentage of GDP per capita, and adjusted net national income per capita of each country. We used meta analysis to calculate WTP means and confidence intervals, and vote-counting to identify the variables that more often affected WTP. RESULT: 16 studies (21 articles) from ten countries met the inclusion criteria. The mean WTP of individuals was 1.18% of GDP per capita and 1.39% of adjusted net national income per capita. The corresponding figures for households were 1.82% and 2.16%, respectively. Increases in family size, education level and income were consistently correlated with higher WTP for insurance, and increases in age were correlated with reduced WTP. CONCLUSIONS: The WTP for healthcare insurance among rural households in LMICs was just below 2% of the GPD per capita. The findings demonstrate that in moving towards universal health coverage in LMICs, governments should not rely on households' premiums as a major financing source and should increase their fiscal capacity for an equitable health care system using other sources. PMID- 27362357 TI - Forms of medical pluralism among the Polish Community in Misiones, Argentina. AB - The paper addresses forms of medical pluralism, studied from the microsocial perspective, among the Polish community in Misiones, Argentina. It shows different attitudes to health treatment within the field of home medicine, local non-biomedical specialists and biomedicine. It points out the relationship between the diversity of offers of medical assistance and community members' negotiations between various medical approaches. It also identifies the factors influencing these choices. While prior research examines Indigenous and Mestizo medical ethnobotany in this region, there has not been research on medical pluralism and very little study of complementary and alternative medicine among the inhabitants of Misiones. The study group comprises Polish peasants who settled in northern Misiones between 1936 and 1938 and their descendants born in Argentina. Field research was based on semi-structured, in-depth and free-listing interviews. The analysis was carried out using both qualitative and quantitative approaches. The results show that Polish settlers tried to reconstruct bits and pieces of their familiar and traditional healing practices in the new environment. Phytotherapy plays the most important role among home therapies. It is at home that most treatments start. Members of the Polish community also treat folk illnesses at home and report them to local healers. The growing influence of biomedicine does not contribute to the elimination of home medicine or non biomedical specialists in the study area. There has been a medicalization of childbirth and fractures, but folk experts such as curanderos, hueseros and naturistas are still very popular in the region. PMID- 27362358 TI - Speech intelligibility assessment of protective facemasks and air-purifying respirators. AB - Speech Intelligibility (SI) is the perceived quality of sound transmission. In healthcare settings, the ability to communicate clearly with coworkers, patients, etc., is crucial to quality patient care and safety. The objectives of this study were to: (1) assess the suitability of the Speech Transmission Index (STI) methods for testing reusable and disposable facial and respiratory personal protective equipment (protective facemasks [PF], N95 filtering facepiece respirators [N95 FFR], and elastomeric half-mask air-purifying respirators [EAPR]) commonly worn by healthcare workers; (2) quantify STI levels of these devices; and (3) contribute to the scientific body of knowledge in the area of SI. SI was assessed using the STI under two experimental conditions: (1) a modified version of the National Fire Protection Association 1981 Supplementary Voice Communications System Performance Test at a Signal to Noise Ratio (SNR) of 15 (66 dBA) and (2) STI measurements utilizing a range of modified pink noise levels (52.5 dBA (-2 SNR) - 72.5 dBA (+7 SNR)) in 5.0 dBA increments. The PF models (Kimberly Clark 49214 and 3 M 1818) had the least effect on SI interference, typically deviating from the STI baseline (no-mask condition) by 3% and 4% STI, respectively. The N95FFR (3 M 1870, 3 M 1860) had more effect on SI interference, typically differing from baseline by 13% and 17%, respectively, for models tested. The EAPR models (Scott Xcel and North 5500) had the most significant impact on SI, differing from baseline by 42% for models tested. This data offers insight into the performance of these apparatus with respect to STI and may serve as a reference point for future respirator design considerations, standards development, testing and certification activities. PMID- 27362360 TI - Nutrition meets the microbiome: micronutrients and the microbiota. AB - There is increasing evidence that food is an important factor that influences and shapes the composition and configuration of the gut microbiota. Most studies have focused on macronutrients (fat, carbohydrate, protein) in particular and their effects on the gut microbiota. Although the microbiota can synthesize different water-soluble vitamins, the effects of vitamins synthesized within the microbiota on systemic vitamin status are unclear. Few studies exist on the shuttling of vitamins between the microbiota and intestine and the impact of luminal vitamins on the microbiota. Studying the interactions between vitamins and the microbiota may help to understand the effects of vitamins on the barrier function and immune system of the intestinal tract. Furthermore, understanding the impact of malnutrition, particularly low micronutrient supply, on microbiota development, composition, and metabolism may help in implementing new strategies to overcome the deleterious effects of malnutrition on child development. This article reviews data on the synthesis of different micronutrients and their effects on the human microbiota, and further discusses the consequences of malnutrition on microbiota composition. PMID- 27362359 TI - Comorbid Depression and Heart Failure: A Community Cohort Study. AB - OBJECTIVE: To examine the association between depression and clinical outcomes in heart failure (HF) in a community cohort. PATIENTS AND METHODS: HF patients in Minnesota, United States completed depression screening using the 9-item Patient Health Questionnaire (PHQ-9) between 1st Oct 2007 and 1st Dec 2011; patients with PHQ-9>=5 were labelled "depressed". We calculated the risk of death and first hospitalization within 2 years using Cox regression. Results were adjusted for 10 commonly used prognostic factors (age, sex, systolic blood pressure, estimated glomerular filtration rate, serum sodium, ejection fraction, blood urea nitrogen, brain natriuretic peptide, presence of diabetes and ischaemic aetiology). Area under the curve (AUC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) compared depression as a predictor against the aforementioned factors. RESULTS: 425 patients (mean age 74, 57.6% males) were included in the study; 179 (42.1%) had PHQ-9>=5. The adjusted hazard ratio of death was 2.02 (95% CI 1.34-3.04) and of hospitalization was 1.42 (95% CI 1.13 1.80) for those with compared to those without depression. Adding depression to the models did not appreciably change the AUC but led to statistically significant improvements in both the IDI (p = 0.001 and p = 0.005 for death and hospitalization, respectively) and NRI (for death and hospitalization, 35% (p = 0.002) and 27% (p = 0.007) were reclassified correctly, respectively). CONCLUSION: Depression is frequent among community patients with HF and associated with increased risk of hospitalizations and death. Risk prediction for death and hospitalizations in HF patients can be improved by considering depression. PMID- 27362361 TI - Gender Differences in Emotional Response: Inconsistency between Experience and Expressivity. AB - The present study investigated gender differences in both emotional experience and expressivity. Heart rate (HR) was recorded as an indicator of emotional experience while the participants watched 16 video clips that induced eight types of emotion (sadness, anger, horror, disgust, neutrality, amusement, surprise, and pleasure). We also asked the participants to report valence, arousal, and motivation as indicators of emotional expressivity. Overall, the results revealed gender differences in emotional experience and emotional expressivity. When watching videos that induced anger, amusement, and pleasure, men showed larger decreases in HR, whereas women reported higher levels of arousal. There was no gender difference in HR when the participants watched videos that induced horror and disgust, but women reported lower valence, higher arousal, and stronger avoidance motivation than did men. Finally, no gender difference was observed in sadness or surprise, although there was one exception-women reported higher arousal when watching videos that induced sadness. The findings suggest that, when watching videos that induce an emotional response, men often have more intense emotional experiences, whereas women have higher emotional expressivity, particularly for negative emotions. In addition, gender differences depend on the specific emotion type but not the valence. PMID- 27362363 TI - Implications of Untreated Cleft Palate in the Developing World: Adaptation of an Outcome Measure. AB - OBJECTIVES: To identify the implications of living with untreated cleft palate and develop an outcome measure which reflects the broad impact of surgery but is sensitive to the physical impact, speech changes, and psychosocial implications of late intervention. Design, Participants, Setting: Focus groups and individual interviews were used to gather information on the implications of living with untreated cleft palate and the impact of subsequent surgery. Participants included 11 individuals attending a cleft department in India whose cleft had persisted into adolescence or adulthood, as well as 16 of their family members. The findings were used to assess whether the Therapy Outcome Measure (TOM) could capture the implications of untreated cleft palate and the impact of surgery beyond that of speech alone. RESULTS: The findings indicated that the implications of living with untreated cleft palate revolved around difficulties with communication, reduced autonomy, and nasal regurgitation. These issues are encapsulated within the third and fourth domains of the TOM, but there is a need for an adapted version (TOM-clp) to use in the developing world, incorporating areas specific to cleft palate. CONCLUSION: The TOM has potential as a global tool for measuring the broad impact, including the psychosocial benefit, from attending to untreated cleft palate. PMID- 27362362 TI - Regulation of the Na+/K+-ATPase Ena1 Expression by Calcineurin/Crz1 under High pH Stress: A Quantitative Study. AB - Regulated expression of the Ena1 Na+-ATPase is a crucial event for adaptation to high salt and/or alkaline pH stress in the budding yeast Saccharomyces cerevisiae. ENA1 expression is under the control of diverse signaling pathways, including that mediated by the calcium-regulatable protein phosphatase calcineurin and its downstream transcription factor Crz1. We present here a quantitative study of the expression of Ena1 in response to alkalinization of the environment and we analyze the contribution of Crz1 to this response. Experimental data and mathematical models substantiate the existence of two stress-responsive Crz1-binding sites in the ENA1 promoter and estimate that the contribution of Crz1 to the early response of the ENA1 promoter is about 60%. The models suggest the existence of a second input with similar kinetics, which would be likely mediated by high pH-induced activation of the Snf1 kinase. PMID- 27362364 TI - Silibinin: a potential old drug for cancer therapy. AB - INTRODUCTION: Silibinin is mixture of flavonolignans extracted from milk thistle and often has been used in the treatment of acute and chronic liver disorders caused by toxins, drug, alcohol and hepatitis and gall bladder disorders for its antioxidant and hepatoprotective properties. AREAS COVERED: However, increasing evidence suggest that silibinin is not solely limited in the treatment of these diseases. Further research suggests that silymarin may function diversely and may serve as a novel therapy for cancer therapy, such as lung cancer, prostatic cancer, colon cancer, breast cancer, bladder cancer and hepatocellular carcinoma by regulating cancer cells growth, proliferation, apoptosis, angiogenesis and many other mechanism. Expert commentary: In this review, in order to provide potential new treatment for these cancer, we summarize the recent anti-cancer findings of silibinin in these cancer and clarify the mechanisms of this effect. PMID- 27362365 TI - A novel surfactant protein C gene mutation associated with progressive respiratory failure in infancy. AB - Mutations of the Surfactant Protein C (SPC) gene (SFTPC) have been associated with childhood interstitial lung disease (chILD) with variable age of onset, severity of lung disease, and outcomes. We report a novel mutation in SFTPC [c.435G->A, p.(Gln145)] that was associated with onset of symptoms in early infancy, progressive respiratory failure with need for prolonged mechanical ventilatory support, and eventual lung transplant at 1 year of age. While the mutation was not predicted to alter the amino acid sequence of the SP-C precursor protein, analysis of SP-C transcripts demonstrated skipping of exon 4. Because of limited data about the outcomes of infants with SFTPC mutations, we conducted a systematic review of all the SFTPC mutations reported in the literature in order to define their presenting features, clinical and radiologic features, and outcomes. Further advances in our understanding of chILD and creation of an international registry will help to track these patients and their outcomes. Pediatr Pulmonol. 2017;52:57-68. (c) 2016 Wiley Periodicals, Inc. PMID- 27362366 TI - ADAR1 deletion induces NFkappaB and interferon signaling dependent liver inflammation and fibrosis. AB - Adenosine deaminase acting on RNA (ADAR) 1 binds and edits double-stranded (ds) RNA secondary structures found mainly within untranslated regions of many transcripts. In the current research, our aim was to study the role of ADAR1 in liver homeostasis. As previous studies show a conserved immunoregulatory function for ADAR1 in mammalians, we focused on its role in preventing chronic hepatic inflammation and the associated activation of hepatic stellate cells to produce extracellular matrix and promote fibrosis. We show that hepatocytes specific ADAR1 knock out (KO) mice display massive liver damage with multifocal inflammation and fibrogenesis. The bioinformatics analysis of the microarray gene expression datasets of ADAR1 KO livers reveled a type-I interferons signature and an enrichment for immune response genes compared to control littermate livers. Furthermore, we found that in vitro silencing of ADAR1 expression in HepG2 cells leads to enhanced transcription of NFkappaB target genes, foremost of the pro inflammatory cytokines IL6 and IL8. We also discovered immune cell-independent paracrine signaling among ADAR1-depleted HepG2 cells and hepatic stellate cells, leading to the activation of the latter cell type to adopt a profibrogenic phenotype. This paracrine communication dependent mainly on the production and secretion of the cytokine IL6 induced by ADAR1 silencing in hepatocytes. Thus, our findings shed a new light on the vital regulatory role of ADAR1 in hepatic immune homeostasis, chiefly its inhibitory function on the crosstalk between the NFkappaB and type-I interferons signaling cascades, restraining the development of liver inflammation and fibrosis. PMID- 27362368 TI - Bioactive properties and potentials cosmeceutical applications of phlorotannins isolated from brown seaweeds: A review. AB - Currently, natural ingredients are becoming more attractive for the industries such as functional food, nutraceuticals, cosmeceutical and pharmaceutical industries as people starting to believe naturally occurring compounds are safer to humans than artificial compounds. Seaweeds are one of the most interesting organisms found in oceans around the earth, which are carrying great ecological importance and contribute to increase the biodiversity of ecosystems where they were originated and habitat. Within last few decades, discovery of secondary metabolites with biological activities from seaweeds has been significantly increased. Further, the unique secondary metabolites isolated from seaweeds including polysaccharides, carotenoids and polyphenols possess range of bioactive properties that make them potential ingredient for many industrial applications. Among those groups of compounds phlorotannins isolated from brown seaweeds have shown interesting bioactive properties including anti-cancer, anti-inflammation, anti-oxidant, anti-allergic, anti-wrinkling and hair growth promotion properties. Moreover, these properties associated with phlorotannins make them an ideal compounds to use as a functional ingredient in cosmeceutical products. Up to now no report has been reviewed about discuss properties of phlorotannins related to the cosmeceutical application. In the present review primary attention is given to the collect scientific data published about bioactive properties of brown algal phlorotannins related to the cosmeceutical industry. PMID- 27362369 TI - A 4:1 stoichiometric binding and stabilization of mitoxantrone-parallel stranded G-quadruplex complex established by spectroscopy techniques. AB - Small molecule ligands which specifically bind and stabilize G-quadruplex structures in telomeric ends inhibit the activity of telomerase enzyme, an important marker for cancer. Understanding of the binding mode of ligand-G quadruplex complex is important for evaluating relative efficacy of anti-tumor drugs. The present study is focused on interaction of anti-tumor drug mitoxantrone (MTX) with tetra-molecular parallel stranded G-quadruplex sequence d TTGGGGT using absorbance, fluorescence and circular dichroism spectroscopy techniques. Absorbance of mitoxantrone shows hypochromism up to MTX (D)/DNA quadruplex (N) ratio ~5, followed by hyperchromism up to D/N=0.21 accompanied by a red shift of 15nm. The fluorescence emission of MTX shows decrease up to D/N ~5 and then increases with red shift of 8nm. The two observed fluorescent lifetimes, 0.17ns (91%) and 0.44ns (9%), indicate dual binding mode. Absence of isobestic and isoemissive point indicates presence of multiple complexes. Circular Dichroism spectra showing positive induced band at 645nm and two exciton bands centered at 619 and 664nm suggest binding of mitoxantrone as a dimer. Proton NMR studies show intermolecular MTX-MTX short contacts confirming existence of stacked dimer of MTX. Thermal melting transitions of DNA saturate at D/N=4 with DeltaTm=25 degrees C. The results establish highly specific external groove binding of 4 molecules of mitoxantrone as two dimers at two distinct sites of DNA. PMID- 27362367 TI - Drug Residues after Intravenous Anesthesia and Intrathecal Lidocaine Hydrochloride Euthanasia in Horses. AB - BACKGROUND: Intrathecal lidocaine hydrochloride under general anesthesia has been used as an alternative method of euthanasia in equids. Carnivore, scavenger, and even human consumption of horse meat from carcasses have been anecdotally reported in rural areas after this method of euthanasia. The presence of drug residues in horse meat has not been investigated. HYPOTHESIS/OBJECTIVES: To investigate if drug residues are found in horse tissues and determine their concentrations. ANIMALS: Of 11 horses requiring euthanasia for medical reasons. METHODS: Prospective descriptive study. Horses were anesthetized with total IV dose of xylazine (mean, 2.5 mg/kg), midazolam (0.1 mg/kg), and ketamine hydrochloride (mean, 5.8 mg/kg). An atlanto-occipital cisterna centesis for the collection of cerebrospinal fluid (CSF) and administration of lidocaine hydrochloride (4 mg/kg) was performed. Blood samples for both serum and plasma, skeletal muscle (triceps brachii, gluteus medius), and CSF were collected for the determination of drug residues. Frozen skeletal muscle available from 5 additional horses that received standard dosages of drugs for short-term anesthesia (xylazine 1.1 mg/kg, midazolam 0.1 mg/kg, and ketamine 2.2 mg/kg) also were analyzed. RESULTS: Drug residues were found in the tissues of all horses, but at extremely low concentrations. CONCLUSIONS AND CLINICAL IMPORTANCE: Euthanasia by administration of lidocaine intrathecally to horses under IV anesthesia poses a low risk of toxicity to carnivores and scavengers that might consume muscle tissue from a carcass in which this protocol has been used. PMID- 27362370 TI - Calcium and protons affect the interaction of neurotransmitters and anesthetics with anionic lipid membranes. AB - We study how zwitterionic and anionic biomembrane models interact with neurotransmitters (NTs) and anesthetics (ATs) in the presence of Ca(2+) and different pH conditions. As NTs we used acetylcholine (ACh), gamma-aminobutyric acid (GABA), and l-glutamic acid (LGlu). As ATs, tetracaine (TC), and pentobarbital (PB) were employed. By using differential scanning calorimetry (DSC), we analyzed the changes such molecules produce in the thermal properties of the membranes. We found that calcium and pH play important roles in the interactions of NTs and ATs with the anionic lipid membranes. Changes in pH promote deprotonation of the phosphate groups in anionic phospholipids inducing electrostatic interactions between them and NTs; but if Ca(2+) ions are in the system, these act as bridges. Such interactions impact the physical properties of the membranes in a similar manner that anesthetics do. Beyond the usual biochemical approach, we claim that these effects should be taken into account to understand the excitatory-inhibitory orchestrated balance in the nervous system. PMID- 27362371 TI - Current Concepts and Controversies in Innate Immunity of Cystic Fibrosis Lung Disease. AB - Cystic fibrosis (CF) lung disease is characterized by chronic infection and inflammation. The inflammatory response in CF is dominated by the activation of the innate immune system. Bacteria and fungi represent the key pathogens chronically colonizing the CF airways. In response, innate immune pattern recognition receptors, expressed by airway epithelial and myeloid cells, sense the microbial threat and release chemoattractants to recruit large numbers of neutrophils into CF airways. However, neutrophils fail to efficiently clear the invading pathogens, but instead release harmful proteases and oxidants and finally cause tissue injury. Here, we summarize and discuss current concepts and controversies in the field of innate immunity in CF lung disease, facing the ongoing questions of whether inflammation is good or bad in CF and how innate immune mechanisms could be harnessed therapeutically. PMID- 27362372 TI - Palladium-Catalyzed Chemoselective and Biocompatible Functionalization of Cysteine-Containing Molecules at Room Temperature. AB - The third generation of aminobiphenyl palladacycle pre-catalyst "G3-Xantphos" enables functionalization of peptides containing cysteine in high yields. The conjugation (bioconjugation) occurs chemoselectively at room temperature under biocompatible conditions. Extension of the method to protein functionalization allows selective bioconjugation of the trastuzumab antibody. PMID- 27362373 TI - Cohesive Energies and Enthalpies: Complexities, Confusions, and Corrections. AB - The cohesive or atomization energy of an ionic solid is the energy required to decompose the solid into its constituent independent gaseous atoms at 0 K, while its lattice energy, Upot, is the energy required to decompose the solid into its constituent independent gaseous ions at 0 K. These energies may be converted into enthalpies at a given temperature by the addition of the small energies corresponding to integration of the heat capacity of each of the constituents. While cohesive energies/enthalpies are readily calculated by thermodynamic summing of the formation energies/enthalpies of the constituents, they are also currently intensively studied by computational procedures for the resulting insight on the interactions within the solid. In supporting confirmation of their computational results, authors generally quote "experimental" cohesive energies which are, in fact, simply the thermodynamic sums. However, these "experimental" cohesive energies are quoted in many different units, atom-based or calorimetric, and on different bases such as per atom, per formula unit, per oxide ion, and so forth. This makes comparisons among materials very awkward. Additionally, some of the quoted values are, in fact, lattice energies which are distinctly different from cohesive energies. We list large numbers of reported cohesive energies for binary halides, chalcogenides, pnictogenides, and Laves phase compounds which we bring to the same basis, and identify a number as incorrectly reported lattice energies. We also propose that cohesive energies of higher-order ionic solids may also be estimated as thermodynamic enthalpy sums. PMID- 27362376 TI - Antimicrobial Resistance (AMR): Why Psychiatric/Mental Health Nurses Need to Have AMR in Their Alphabet. PMID- 27362377 TI - Transition-Aged Youths and the Effect on Executive Functioning. PMID- 27362374 TI - In ovo exposure to monochromatic lights affect posthatch muscle growth and satellite cell proliferation of chicks: role of IGF-1. AB - To study the role of IGF-1 on stimulation with monochromatic light during incubation altering posthatch muscle growth, chicken embryos were exposed to blue light, green light, red light, white light or darkness throughout embryonic period and then were raised in white light conditions upon hatching. Comparing with the other treatment groups, the chicks in green light group had heavier hatching weights, higher muscle indexes and larger muscle fibers. Both in vivo and in vitro studies showed that the number and proliferative activity of satellite cells in green light group were the highest. Plasma IGF-1 level and skeletal muscle IGF-1R mRNA level were higher in green light group. Moreover, exogenous IGF-1 increased the proliferative activity of satellite cell in a dose dependent fashion. These results suggest that stimulation with monochromatic green light during incubation promoted posthatch muscle growth and satellite cell proliferation of chicks through IGF-1 signaling. PMID- 27362380 TI - Drugs to Treat Depression. PMID- 27362381 TI - Antidepressant, Antipsychotic, and Hallucinogen Drugs for the Treatment of Psychiatric Disorders: A Convergence at the Serotonin-2A Receptor. AB - Antidepressant, atypical antipsychotic, and hallucinogen drugs mediate their actions in part by interactions with the serotonin-2A (5HT2A) receptor. Serotonergic hallucinogen drugs, such as psilocybin, bind most potently as agonists at the 5HT2A receptor, producing profound changes in perception, mood, and cognition. Some of these drugs have been or are currently being investigated in small Phase 2 studies for depression, alcoholism, smoking cessation, anxiety, and posttraumatic stress disorder. However, unlike the synergistic effects of combining antidepressant and atypical antipsychotic drugs, the potential therapeutic effects of hallucinogen drugs may be attenuated by the concurrent use of these medications because antidepressant and atypical antipsychotic drugs desensitize and/or down-regulate 5HT2A receptors. This finding has important implications for optimizing the potential therapeutic use of hallucinogen drugs in psychiatry. [Journal of Psychosocial Nursing and Mental Health Services, 54(7), 21-24.]. PMID- 27362382 TI - Adopting a Clinical Assessment Framework in Older Adult Mental Health. AB - Obtaining new knowledge accepted and used by practitioners remains a slow process. A dearth of knowledge translation research exists that explores how to effectively move knowledge to practice in the field of older adult mental health. The current article reports findings of a knowledge translation study that examined what factors enabled the adoption of a new clinical assessment framework, P.I.E.C.E.S.TM, into practice in an older adult tertiary mental health unit. Theoretical insights of appreciative inquiry were used to guide the study. Qualitative methods were used, including focus groups with 20 staff and individual interviews with three leaders. The appreciative inquiry approach helped researchers successfully facilitate knowledge translation. Enabling factors included: (a) fostering positive energy to make continuous improvement, (b) working with team members across disciplines at all levels, and (c) using knowledge translation tools to enable and sustain the new practice. [Journal of Psychosocial Nursing and Mental Health Services, 54 (7), 26-31.]. PMID- 27362383 TI - Psychiatric Inpatient Bedside Handoff: Implementation of a Quality Improvement Project and Nurses' Responses. AB - Psychiatric inpatient unit nurses implemented a quality improvement project to explore strategies to enhance the effectiveness of the change of shift communication between nurses and patients and obtain goals of care information. Three nurses championed a 6-month project to implement more efficient, patient centered communication; influence patient outcomes; and assess nurses' perceptions about patient satisfaction. A survey established the level of nurse satisfaction regarding the length of time spent at change of shift obtaining patient information. Following a literature review, nurses used a standardized approach for their change of shift report, which they called patient bedside handoff. Nurses reported increased satisfaction with the length of time spent with the patient bedside handoff from a pre-implementation average score of 5.7 (somewhat satisfied) to a post-implementation score of 8.3 (very satisfied). This nurse-led quality improvement project helped illuminate perceived barriers to the implementation of patient bedside handoff and the changes in nurses' perceptions over time. [Journal of Psychosocial Nursing and Mental Health Services, 54(7), 33 37.]. PMID- 27362384 TI - Advocating for the Use of Pharmacogenomics: One Nurse's Story. AB - The current article describes the experiences of a motivated nurse who gained an understanding of pharmacogenomics and advocated for the use cytochrome P450 testing for patients in her clinical practice, her family members, herself, and for changing the health care delivery system to more readily recognize and address drug-metabolizing-enzyme abnormalities. Recommendations for nurses interested in promoting the use of pharmacogenomics include learning as much as possible about testing and implications, networking with other providers, identifying a knowledgeable pharmacist, assessing for a family history of problems with medication side effects or lack of efficacy, and keeping records of relevant medical and medication information to share with providers. [Journal of Psychosocial Nursing and Mental Health Services, 54(7), 38-42.]. PMID- 27362385 TI - Effect of the Cognitive-Behavioral Prevention Program on Levels of Depression Symptoms Among Working Adolescents in Turkey. AB - The current study was conducted to determine the effect of the Cognitive Behavioral Prevention Program (CBPP) on levels of depression symptoms, ability to cope with stress, and automatic negative thought patterns among working adolescents in Turkey. The CBPP was conducted once per week for eight sessions and then once per month for six sessions. Data were collected using the Beck Depression Inventory, Automatic Thoughts Questionnaire, and Rosenbaum's Learned Resourcefulness Schedule. Observations were made prior to administration of the CBPP, upon conclusion of the program, and at 6 and 12 months. Chi-square and t tests were used for data analysis. Mean age of participants was 15.85, and they worked a mean 10.84 hours per day. After taking part in the CBPP, participants displayed a decrease in levels of depression symptoms, an increase in their ability to cope with stress, and diminished automatic negative thoughts (all p = 0.001), thus indicating that they benefited from the program and its effectiveness continued through 12-month follow up. [Journal of Psychosocial Nursing and Mental Health Services, 54(7), 43-51.]. PMID- 27362387 TI - Machine Learning Techniques in Clinical Vision Sciences. AB - This review presents and discusses the contribution of machine learning techniques for diagnosis and disease monitoring in the context of clinical vision science. Many ocular diseases leading to blindness can be halted or delayed when detected and treated at its earliest stages. With the recent developments in diagnostic devices, imaging and genomics, new sources of data for early disease detection and patients' management are now available. Machine learning techniques emerged in the biomedical sciences as clinical decision-support techniques to improve sensitivity and specificity of disease detection and monitoring, increasing objectively the clinical decision-making process. This manuscript presents a review in multimodal ocular disease diagnosis and monitoring based on machine learning approaches. In the first section, the technical issues related to the different machine learning approaches will be present. Machine learning techniques are used to automatically recognize complex patterns in a given dataset. These techniques allows creating homogeneous groups (unsupervised learning), or creating a classifier predicting group membership of new cases (supervised learning), when a group label is available for each case. To ensure a good performance of the machine learning techniques in a given dataset, all possible sources of bias should be removed or minimized. For that, the representativeness of the input dataset for the true population should be confirmed, the noise should be removed, the missing data should be treated and the data dimensionally (i.e., the number of parameters/features and the number of cases in the dataset) should be adjusted. The application of machine learning techniques in ocular disease diagnosis and monitoring will be presented and discussed in the second section of this manuscript. To show the clinical benefits of machine learning in clinical vision sciences, several examples will be presented in glaucoma, age-related macular degeneration, and diabetic retinopathy, these ocular pathologies being the major causes of irreversible visual impairment. PMID- 27362388 TI - Ultrafast Spectroscopic Signatures of Coherent Electron-Transfer Mechanisms in a Transition Metal Complex. AB - The prevalence of ultrafast electron-transfer processes in light-harvesting materials has motivated a deeper understanding of coherent reaction mechanisms. Kinetic models based on the traditional (equilibrium) form of Fermi's Golden Rule are commonly employed to understand photoinduced electron-transfer dynamics. These models fail in two ways when the electron-transfer process is fast compared to solvation dynamics and vibrational dephasing. First, electron-transfer dynamics may be accelerated if the photoexcited wavepacket traverses the point of degeneracy between donor and acceptor states in the solvent coordinate. Second, traditional kinetic models fail to describe electron-transfer transitions that yield products which undergo coherent nuclear motions. We address the second point in this work. Transient absorption spectroscopy and a numerical model are used to investigate coherent back-electron-transfer mechanisms in a transition metal complex composed of titanium and catechol, [Ti(cat)3](2-). The transient absorption experiments reveal coherent wavepacket motions initiated by the back electron-transfer process. Model calculations suggest that the vibrationally coherent product states may originate in either vibrational populations or coherences of the reactant. That is, vibrational coherence may be produced even if the reactant does not undergo coherent nuclear motions. The analysis raises a question of broader significance: can a vibrational population-to-coherence transition (i.e., a nonsecular transition) accelerate electron-transfer reactions even when the rate is slower than vibrational dephasing? PMID- 27362389 TI - Up-regulation of neural indicators of empathic concern in an offender population. AB - Empathic concern has traditionally been conceived of as a spontaneous reaction to others experiencing pain or distress. As such, the potential role of more deliberate control over empathic responses has frequently been overlooked. The present fMRI study evaluated the role of such deliberate control in empathic concern by examining the extent to which a sample of offenders recruited through probation/parole could voluntarily modulate their neural activity to another person in pain. Offenders were asked to either passively view pictures of other people in painful or non-painful situations, or to actively modulate their level of concern for the person in pain. During passive viewing of painful versus non painful pictures, offenders showed minimal neural activity in regions previously linked to empathy for pain (e.g., dorsal anterior cingulate cortex and bilateral insula). However, when instructed to try to increase their concern for the person in pain, offenders demonstrated significant increases within these regions. These findings are consistent with recent theories of empathy as motivational in nature, and suggest that limitations in empathic concern may include a motivational component. PMID- 27362390 TI - Comparative effectiveness and safety of antazoline-based and propafenone-based strategies for pharmacological cardioversion of short-duration atrial fibrillation in the emergency department. AB - INTRODUCTION Numerous studies described the effectiveness and safety of antazoline in pharmacological cardioversion of short-duration atrial fibrillation (AF). However, there are no data on the comparison of antazoline and antiarrhythmic drugs listed in clinical guidelines. OBJECTIVES The aim of the study was to assess the comparative effectiveness and safety of antazoline-based and propafenone-based strategies in pharmacological cardioversion of short duration AF performed in our emergency department. PATIENTS AND METHODS We conducted a retrospective case-control study based on the analysis of medical records of patients undergoing pharmacological cardioversion of short-duration AF with intravenous antazoline or propafenone at our department in the years 2008 2012. The primary endpoint was the successful cardioversion of AF. The primary safety endpoint was hospitalization due to the adverse effects of the treatment. RESULTS We analyzed 432 cases of cardioversion. The mean age of patients was 68.9 +/-9.8 years; 65% of the patients were male; 90% of the patients had a history of AF. Antazoline was administered 334 times and propafenone-98 times. The mean dose of antazoline was 172 +/-65 mg, while all patients in the propafenone group received the drug at a fixed dose of 70 mg (1 vial). Cardioversion with antazoline was successful in 239 cases (71.6%) and with propafenone-in 54 patients (55.1%) (relative risk [RR], 1.30; 95% confidence interval [CI], 1.07-1.57). The rate of hospitalization due to the adverse effects of the treatment were low and similar between the study groups: 10 (3.0%) for antazoline and 4 (4.1%) for propafenone (RR, 0.73; 95% CI, 0.23-2.27). CONCLUSIONS The antazoline-based strategy was more effective and safer in comparison with propafenone-based strategy in the pharmacological cardioversion of short-duration AF in our emergency department. PMID- 27362391 TI - Factors related to the effectiveness of hypercholesterolemia treatment following hospitalization for coronary artery disease. AB - INTRODUCTION Patients with established coronary artery disease (CAD) are at high risk of recurrent cardiovascular events. OBJECTIVES The aim of the study was to identify factors related to control of hypercholesterolemia in patients after hospitalization for CAD. PATIENTS AND METHODS The study included consecutive patients from 5 hospitals with cardiology departments serving one city in southern Poland. Patients were hospitalized for an acute coronary syndrome or for a myocardial revascularization procedure. Interviews and examinations were conducted 6 to 18 months after hospitalization. RESULTS Overall, 83.6% of the patients were taking statins; 2.1%, fibrates; and 0.5%, ezetimibe. A statin at a high dose (>=40 mg of atorvastatin or >=20 mg of rosuvastatin) was taken by 36.1% of the participants. Younger age and index hospitalization in a teaching hospital were significantly associated with a higher probability of taking a statin. Overall, 28.1% of the patients had good control of hypercholesterolemia (low-density lipoprotein [LDL] cholesterol levels <1.8 mmol/l), whereas 71.9%, 38.6%, 24.4%, and 10.3% had LDL cholesterol levels of 1.8 mmol/l or higher, 2.5 mmol/l or higher, 3.0 mmol/l or higher, and 4.0 mmol/l or higher, respectively. Younger age, high blood pressure, and high fasting glucose levels were related to a higher probability of having LDL cholesterol levels of 1.8 mmol/l or higher, while younger age, shorter period of education, professional inactivity, lack of cardiac rehabilitation, and high blood pressure were related to the probability of LDL cholesterol levels of 4.0 mmol/l or higher. CONCLUSIONS The frequency of statin use is affected by age and health care-related factors, while control of hypercholesterolemia after hospitalization due to CAD is dependent mainly on patient-related and clinical factors. PMID- 27362392 TI - Prognostic value of coronary artery calcium score in patients with symptoms suggestive of coronary artery disease. Results from the Silesian Calcium Score (SILICAS) study. AB - INTRODUCTION The prognostic value of coronary artery calcium score (CACS) in symptomatic patients with a suspicion of coronary artery disease (CAD) has been poorly defined. OBJECTIVES The aim of the study was to assess the predictive value of the CACS in the incidence of major adverse coronary events (MACEs) in patients with an intermediate probability of CAD and establish its usefulness as the first-line risk assessment tool. PATIENTS AND METHODS This single-center, observational, prospective study enrolled consecutive symptomatic patients without a previous diagnosis of CAD, referred to our center for CACS assessment with non-contrast-enhanced cardiac computed tomography (CT). CACS measurements were performed using an electrocardiogram-gated 64-row CT scanner. The CACS measurement was treated as the first-line noninvasive test. Patients with positive CACS values were divided into 4 subgroups: <100 Agatston units (AU), 100 to 399 AU; 400 to 999 AU; and >=1000 AU. The incidence of MACEs was analyzed in 2 ways: negative versus positive CACS and by the CACS subgroups. RESULTS We included 588 patients (mean age, 61.1 +/-9.7 years; women, 64%). The median follow-up period was 707 days. There were 239 patients (49.3%) with no coronary calcium. In these patients, no MACEs were observed, while in those with positive CACS values, they occurred in 108 patients (30.9%) (P <0.001). The incidence of MACEs was dependent on the CACS values, reaching 91% in those with a CACS of 1000 or higher AU. CONCLUSIONS In selected symptomatic patients with an intermediate probability of CAD, the CACS measurement may be used as the first line test to assess the risk of MACEs. PMID- 27362393 TI - Relationship between the thickness of bronchial wall layers, emphysema score, and markers of remodeling in bronchoalveolar lavage fluid in patients with chronic obstructive pulmonary disease. AB - INTRODUCTION Airway remodeling plays an important role in the development of chronic obstructive pulmonary disease (COPD). Imaging methods, such as computed tomography (CT) and endobronchial ultrasound (EBUS), may be useful in the assessment of structural alterations in the lungs. OBJECTIVES The aim of this study was to evaluate a relationship between the severity of emphysema assessed by chest CT, the thickness of bronchial wall layers measured by EBUS, and the markers of remodeling in bronchoalveolar lavage fluid (BALF) in patients with COPD. PATIENTS AND METHODS The study included 33 patients with COPD who underwent pulmonary function tests, emphysema score assessment by chest CT, as well as bronchofiberoscopy with EBUS in order to measure the total bronchial wall thickness and, separately, layers L1, L2, and L3-5. Selected remodeling (matrix metalloproteinase 9 [MMP-9], tissue inhibitor of metalloproteinase 1, transforming growth factor beta1 [TGF-beta1]) and inflammatory markers (neutrophil elastase, eosinophil cationic protein) were measured in BALF samples using an enzyme-linked immunosorbent assay. RESULTS MMP-9 levels in BALF were significantly higher in patients with very severe bronchial obstruction than in those with moderate and mild bronchial obstruction (P = 0.02), and showed a negative correlation with forced expiratory volume in 1 second (r = -0.538, P = 0.002). The thickness of L1 and L2, which histologically correspond to the mucosa, submucosa, and smooth muscle, demonstrated a positive correlation with TGF-beta1 levels in BALF (r = 0.366, P = 0.046 and r = 0.425, P = 0.02) and the thickness of L1 showed a negative association with neutrophil elastase levels (r = -0.508, P = 0.004). There was no significant correlation between the analyzed markers in BALF and the emphysema score. CONCLUSIONS Significant correlations of TGF-beta1 and elastase with the thickness of bronchial wall layers, and of MMP 9 with the severity of obstruction, may suggest the involvement of these markers in airway remodeling in patients with COPD. PMID- 27362394 TI - Targeting blood pressure in people with diabetes mellitus. AB - Hypertension is a strong risk factor for cardiovascular (CV)-related morbidity and mortality, and its treatment has been shown to be beneficial. Hypertension is common in people with diabetes mellitus, and the combination of these conditions markedly increases CV risk in comparison with individuals with neither condition. Although there is increasing clarity as to blood pressure (BP) targets in numerous conditions, the target in people with diabetes remains unclear, and, as a result, many clinical practice guidelines differ on the optimal BP goal. The ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial did not demonstrate benefit when systolic BP (SBP) was lowered to less than 120 mmHg compared with a target of less than 140 mmHg. This was in contrast to the recent SPRINT trial (Systolic Blood Pressure Intervention Trial), which demonstrated the superiority of a target SBP of less than 120 mmHg in reducing CV events. However, people with diabetes mellitus were excluded. Recent meta-analyses have suggested that lowering BP in patients with diabetes mellitus should be reserved for a baseline SBP greater than 140 mmHg, targeting an SBP of between 130 and 140 mmHg. Lower targets may reduce the risk of stroke but may also be harmful with respect to other important CV outcomes. The methodological limitations of these meta analyses highlight the need for a large randomized controlled trial comparing lower and standard BP targets in people with diabetes mellitus. PMID- 27362395 TI - Heparins in cancer-associated venous thrombosis. AB - A close causal relationship between cancer and venous thrombosis gives rise to questions about the effect of treatment modalities, in particular of the administered drugs, in patients with cancer-related venous thrombosis. An increased risk of chemotherapy-associated venous thromboembolism (VTE) has been well documented, while the effect of heparins used in VTE treatment on the disease course and prognosis in cancer patients has not been fully elucidated. This paper discusses the outcomes of the studies conducted so far investigating the role of heparins, in particular, low-molecular-weight heparins (LMWHs), in the prevention of thrombosis in cancer patients. It also focuses on such aspects of the treatment for cancer-associated VTE as treatment duration and drugs used. The paper summarizes the often discrepant results of long-term therapies with various LMWH products, emphasising that in this specific case the class effect is rather unlikely. It also presents the possible effects of heparins administered as part of cancer treatment, and points to the effects of LMWHs on cancer that are not related to an antithrombotic effect. On the 100th anniversary of heparin discovery, it can be said that heparin is irreversibly connected with thrombosis in the course of cancer. PMID- 27362396 TI - Thyroid goiter: implications for implantation of cardiovascular implantable electronic devices and cannulation of the superior vena cava confluence. PMID- 27362397 TI - Does diabetes alter the risk of neoplasms? Real-world data analysis in Poland: incidence rates for selected neoplasms in patients with diabetes. PMID- 27362398 TI - Three-dimensional honeycomb-like structured zero-valent iron/chitosan composite foams for effective removal of inorganic arsenic in water. AB - A facile freeze-drying method was presented to fabricate three dimensional (3D) honeycomb-like structured nanoscale zero-valent iron/chitosan composite foams (ICCFs) for effective removal of inorganic arsenic in water. It was found that freezing temperature has important influence on the formation of 3D network structure of ICCFs. The ICCFs obtained at freeze temperature of -80 degrees C exhibits oriented porous structure with good mechanical property than that at -20 degrees C, thus improved excellent removal capability of As(III) and As(V) up to 114.9mgg(-1) and 86.87mgg(-1), respectively. Further, the adsorption kinetics of ICCFs on As(III) and As(V) can be described by pseudo-second order model and their adsorption isotherms follow Langmuir adsorption model. The superior removal performance of ICCFs on As(III) and As(V) can be ascribed to its oriented porous structure with abundant adsorption active sites resulted from nZVI and O, N containing functional groups in ICCFs. Importantly, it was found that the O, N containing functional groups of chitosan in ICCFs can adequately bind with the dissolved Fe(3+) ions from oxidation of nZVI to form Fe(3+)-Chitosan complex during removal of As(III) and As(V), thus effectively avoiding the dissolved Fe(3+) ions into solution to produce secondary pollution. A possible adsorption coupled reduction mechanism of ICCFs on As(III) and As(V) was also proposed based on the experimental results. We believe that this work would be helpful to develop low-cost and abundant chitosan-based materials as high performance adsorbents for environmental remediation applications. PMID- 27362399 TI - Adsorption of toxic carbamate pesticide oxamyl from liquid phase by newly synthesized and characterized graphene quantum dots nanomaterials. AB - Graphene quantum dots have been synthesized using the microwave-assisted hydrothermal route. The surface textural and morphological structure of synthesized adsorbent i.e. graphene quantum dots was analyzed using various analytical techniques such as X-ray diffraction, Transmission electron Microscopy, Atomic Force Microscopy and N2 adsorption-desorption instrumental techniques. The application of graphene quantum dots as an adsorbent for the removal of noxious pesticide compound i.e. oxamyl from aqueous solutions was well investigated and elucidated. The impact of several effective parameters such as effect of agitation speed, pH, adsorbent dose, contact time, temperature and initial concentration on sorption efficiency was studied and optimized using batch adsorption experiments. The optimized pH for maximum oxamyl adsorption was found to be 8.0 and for the maximum adsorption rates the adsorbent dose of 0.6g was found to be optimum to carry out the adsorption with in less than 25min of contact time. From the results obtained, it is clear that for all contact times, an increase in oxamyl concentration resulted in increase in the percent oxamyl removal. The adsorption equilibrium and kinetic data were well fitted and found to be in good agreement with the Langmuir isotherm and pseudo-second-order kinetic model. PMID- 27362400 TI - Effects of seasonal smog on asthma and COPD exacerbations requiring emergency visits in Chiang Mai, Thailand. AB - BACKGROUND: Seasonal smog produces particulate matters that are less than 10 microns in diameter (PM10), which are known to have several impacts on the respiratory system. OBJECTIVE: This study was to determine the association of an increased PM10 level due to seasonal smog in Chiang Mai and emergency visits for asthma and chronic obstructive pulmonary disease (COPD) exacerbations. METHOD: A retrospective cross-sectional study was conducted between the months of January and March from 2006 until 2009. The association of an increased PM10 level and the daily number of asthma and COPD exacerbations were analyzed using a generalized linear model; a Poisson regression model was fit to the number of daily emergency visits using predictor variables: lags of PM10, day of the week, and time. RESULTS: There were a total of 917 emergency visits for acute exacerbations of asthma and COPD, with a median of 2 visits per day (range 0-10). The median PM10 level during the same interval was 64.5 microgram per cubic meter (MUg/m3) (16-304). For every 10 MUg/m3 rise in PM10 concentration, there was a lag time of 6 days for asthma exacerbations [Adjusted relative risk (RR)=1.020; 95% confident interval (CI), 1.001-1.040; (p=0.014)], 7 days for COPD exacerbations [RR=1.030; 95%CI, 1.010-1.050 (p=0.024)] and 7 days for all exacerbations [RR=1.030 95%CI, 1.010-1.040 (p<0.001)]. CONCLUSIONS: This study confirms the effect of increasing PM10 concentrations from seasonal smog on asthma and COPD exacerbations. However, there was an approximately 1 week lag time between the elevated PM10 levels and time to emergency visits due to disease exacerbation. PMID- 27362401 TI - Comparison between specific IgE levels and skin prick test results of local and imported American cockroach, dog, cat, dust mites and mold allergen extracts. AB - BACKGROUND: Skin prick test (SPT) and specific IgE (sIgE) are approved for evaluation of allergen sensitization. Local allergen extracts are less expensive and more available but need to be standardized. OBJECTIVE: To compare SPT results of local and imported allergen extracts and sIgE levels in response to the American cockroach, dog, cat, Dermatophagoides pteronyssinus (Dp), Dermatophagoides farinae (Df) and Cladosporium spp. allergens. METHOD: This prospective, randomized, double-blind, self-controlled study was performed in respiratory allergic volunteers. Each subject was pricked with local and imported allergen extracts and sIgE levels were measured. RESULTS: The agreement between SPT results from each local and imported allergen extract was statistically significant, and the level of agreement for dog allergens was very good (kappa > 0.8). All patients with a positive SPT in response to imported Dp allergen extract had positive SPT in response to local Dp allergen extract. Mean wheal diameter of each allergen in both groups showed significant correlation with sIgE levels. The correlation coefficient (CC) for cat allergens showed a very good-to excellent relationship (CC> 0.75). When compared with sIgE levels, SPT results for imported and local allergen extracts showed comparable sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio (LR)+ and LR-. CONCLUSIONS: When the SPT results are compared between local and imported allergen extracts, all were found to have significant agreement, with very good agreement for cat allergens. When the SPT results are compared with specific IgE levels, both local and imported allergen extract provided comparable validity. PMID- 27362402 TI - Comparison of different local and imported histamine concentrations used as a skin prick test positive control. AB - BACKGROUND: The skin prick test (SPT) is a valid and approved tool that is used to diagnose atopic diseases. The SPT is accurate, safe, simple and inexpensive. However, the histamine concentration used as a positive control in the SPT varies among centers. OBJECTIVE: To compare SPT results using different concentrations of locally-prepared and imported histamine solutions. METHOD: This prospective, randomized, double-blind, self-controlled study was performed in healthy adult volunteers. The SPT was performed using 4 concentrations of histamine solutions (imported, 1 mg/mL; locally-prepared, 1, 5 and 10 mg/mL). Locally-prepared histamine positive controls were prepared from histamine biphosphate monohydrate using sterile technique. RESULTS: Seventy-five adult volunteers (mean age, 36 years) were included in the study. Eight volunteers were male and 9 had a history of atopy. Mean wheal diameter (MWD) for imported histamine was 3.49 mm for a concentration of 1 mg/mL, and that of locally-prepared histamine was 2.94 mm, 5.05 mm and 5.52 mm for concentrations of 1, 5 and 10 mg/mL histamine, respectively. Negative SPT results (MWD <3 mm) were found in 11 subjects (14.7%) who received imported histamine and 26 subjects (34.7%) who received the locally prepared histamine at concentration of 1 mg/mL. All subjects tested with locally prepared histamine at concentrations of 5 and 10 mg/mL had a MWD > 3 mm. CONCLUSIONS: Locally-prepared histamine base at concentrations of 5 and 10 mg/mL yielded better positive results than both imported and locally-prepared histamine at a concentration of 1 mg/mL. PMID- 27362404 TI - Patterns and risk factors of causative contact allergens in Thai adult patients with contact dermatitis AB - BACKGROUND: Surveillance on common allergens identified by patch testing plays an important role in emerging allergen detection, which leads to both individual and societal level prevention. OBJECTIVE: To study the changes in the pattern of contact sensitization and to identify risk factors associated with allergens. METHOD: The data of 206 patients who underwent patch testing at King Chulalongkorn Memorial Hospital during 2012 to 2015 were assessed. The associations between patient risk factors and positive reactions to each allergen were evaluated. The results were compared with data from 2003-2004. RESULTS: The top five most common allergens during 2012-2015 were nickel sulfate (19.4%), methylchloroisothiazolinone/ methylisothiazolinone (MCI/MI) (13.6%), fragrance mix I (FM I) (10.7%), carba mix (9.2%) and cobalt chloride (6.3%) whereas, during 2003-2004, these were nickel sulfate, cobalt chloride, FM I, potassium dichromate and Myroxylon pereirae. A positive patch test to nickel was strongly associated with a history of metal and seafood allergy (p<0.001; OR, 4.94; 95% CI = 2.33 10.47 and p=0.028; OR, 2.55; 95% CI, 1.11-5.85, respectively). MCI/MI was correlated with a history of personal care products allergy, and fragrance was correlated with a history of urticaria (p=0.005; OR, 4.05; 95% CI = 1.54-10.66 and p=0.031; OR, 2.71; 95% CI, 1.10-6.68, respectively). CONCLUSIONS: There was an alteration in the pattern of contact sensitization detected by our standard series. MCI/MI has become the most common preservative causing contact allergy. PMID- 27362403 TI - Fraction of exhaled nitric oxide and soluble receptors for advanced glycation end products are negatively correlated in children with recurrent wheezing. AB - BACKGROUND: The fraction of exhaled nitric oxide (FeNO) and serum levels of the soluble receptor for advanced glycation end products (sRAGE) have been suggested as biomarkers for asthma. OBJECTIVE: This study aimed to assess the correlation between FeNO and sRAGE serum levels in children <5 years old with recurrent wheezing. METHOD: In total, 88 children with recurrent wheezing were divided into the high-risk group or low-risk group according to their clinical features. The high-risk group included 60 children, 42 male and 18 female, average age 36.7 months (range 32-48.7 months); the low-risk group included 28 children, 20 male and 8 female, average age 38.1 months (range 33-46.2 months).Asthma in high-risk children was treated with aerosol inhalation of Pulmicort respules 1 mg/d for four continuous weeks, while asthma in low-risk children was treated with symptomatic treatment. FeNO, serum sRAGE and eosinophils (EOS) were examined by ELISA and a regular blood cell analyzer. RESULTS: The serum sRAGE level was 738+/ 191 and 992.4+/-210 pg/ml and the mean FeNO level was 27.3 and 17.6 ppm, respectively, in the asthma high-risk and low-risk group, showing significant differences between the two groups. In addition, FeNO and sRAGE serum levels were negatively correlated.After the inhalation of Pulmicort respules, FeNO decreased and sRAGE increased, while EOS showed no significant change. CONCLUSIONS: FeNO and sRAGE serum levels are negatively correlated in children with recurrent wheezing. Further larger scale studies are needed to test the use of FeNO and sRAGE as biomarkers for the prediction of asthma in children. PMID- 27362405 TI - The correlation of serum eosinophil cationic protein level with eosinophil count, and total IgE level in Korean adult allergic rhinitis patients. AB - BACKGROUND: Eosinophil cationic protein (ECP) is present in eosinophil granules. It has been associated with eosinophil-associated disorders. OBJECTIVE: We compared serum ECP levels in allergic and non-allergic rhinitis patients and evaluated the association with the eosinophil count and the total IgE level. METHOD: We retrospectively reviewed medical records and categorized enrolled patients into the allergic (AR) and non-allergic rhinitis (NAR) groups. ECP, eosinophil count, and total IgE levels were reviewed in both groups. The association between ECP and the eosinophil count and total IgE level was further evaluated according to commonly detected specific antigens. RESULTS: Six hundred and ten adults were included in the study. In the AR group (n=349), the median age was 27.0(23.0-42.0) years and the female:male ratio was 0.26:1. In the NAR group (n=261), the median age was 32.0(24.0-45.5) years and the female:male ratio was 0.33:1. We found that ECP (AR: 18.8(9.9-31.4), NAR: 14.8(8.2-24.9), p=0.003), eosinophil count (AR: 191.0(112.0-308.5), NAR: 149.0(91.0-249.0), p=0.002) and total IgE (AR: 166.0(58.4-422.5), NAR: 68.8(24.5-141.0), p<0.001) were higher in AR than in NAR patients. The ECP level was associated with the eosinophil count in both the AR (p<0.001) and NAR groups (p<0.001). A significant correlation between the ECP level and eosinophil count was demonstrated in AR patients who were skin test positive against house dust mite, animal and pollen allergens. CONCLUSIONS: We suggest that ECP could be an important mediator in the pathogenesis of AR. The level of serum ECP was positively correlated with eosinophilia in AR patients regardless of the type of allergen sensitization. However, further study is warranted to verify the role of ECP in the clinical management of allergic rhinitis. PMID- 27362406 TI - Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients. AB - BACKGROUND: Mast cells (MCs) mediate inflammation through neuropeptides and cytokines, along with histamine and reactive oxygen species (ROS). Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is an illness characterized by an unexplained disabling fatigue with multiple physiological impairments as well as dysregulated cytokine profiles. OBJECTIVE: To determine mast cell phenotypes in isolated human PBMCs, in healthy controls and in CFS/ME patients. Second, determine receptor expression of RAGE and its ligand high mobility group box 1 protein (HMGB1). METHOD: Moderately severe CFS/ME patients (n=12, mean age 39.25 +/- SD3.52 years), severe CFS/ME patients (n=6, mean age 43.00 +/- SD4.02 years) and healthy controls (n=13, mean age 42.69 +/- SD3.87 years) were included in this study. CFS/ME patients were classified according to the 2011 International Consensus Criteria. LSRFortessa X-20 Flow cytometry was used for the identification of phenotypic peripheral mast cell population in PBMCs using an exclusion marker Lin2 cocktail (anti-CD3, anti-CD14, anti-CD19, anti-CD20 and anti-CD56) and inclusion markers (CD117, CD34, FCepsilonRI, chymase, HLA-DR and CD154) following comparative investigation. HMGB1 and soluble RAGE expression in plasma was measured by sandwich ELISA assay. RESULTS: There was a significant increase in CD117+CD34+FCepsilonRI-chymase- mast cell populations in moderate and severe CFS/ME patients compared with healthy controls. There was a significant increase in CD40 ligand and MHC-II receptors on differentiated mast cell populations in the severe CFS/ME compared with healthy controls and moderate CFS/ME. There were no significant differences between groups for HMGB1 and sRAGE. CONCLUSIONS: This preliminary study investigates mast cell phenotypes from PBMCs in healthy controls. We report significant increase of naive MCs in moderate and severe CFS/ME patients compared with healthy controls. Moreover, a significant increase in CD40 ligand and MHC-II receptors on differentiated mast cells in severe CFS/ME patients. Peripheral MCs may be present in CFS/ME pathology however, further investigation to determine their role is required. PMID- 27362407 TI - Effect of the prenatal maternal environments and diets on cord blood interleukin 4 and interferon -gamma: A pilot study. AB - BACKGROUND AND OBJECTIVE: TThe environment of a pregnant woman can affect not only fetal growth and development, but also diseases in childhood. Neonatal cord blood cytokines are commonly used to evaluate the immune development of neonates. The purpose of this study was to evaluate the effects of the environment and diet during pregnancy on IL-4 and IFN-gamma in neonatal cord blood. METHOD: A total of 111 pregnant women participated in this study from April to November 2010. Allergy history, sensitization assessed by the skin prick test, dietary intake and indoor environment were evaluated. IL-4 and IFN-gamma levels were measured in the complete cord blood of neonates using real-time PCR. RESULTS: There were 54 pregnant women with allergic disease. Both IL-4 and IFN-gamma levels in neonatal cord blood were higher in samples from allergic mothers than in non-allergic mothers (p<0.05). The indoor environment and nutrient intake were not different between allergic and non-allergic mothers, except regarding carpet use. When the cytokine levels were divided into quartiles, lower folate and vitamin B6 intake was associated with the highest levels of IL-4 in neonatal cord blood (p<0.05), and higher folate and vitamin B6 intake was associated with highest levels of IFN gamma in neonatal cord blood. CONCLUSIONS: In this study, a strong association between IL-4 and IFN-gamma levels in cord blood and the intake of folate and vitamin B6 was found, which indicates that food intake during pregnancy might have a strong influence on IL-4 and IFN-gamma levels in cord blood, to a greater extent than environmental factors. PMID- 27362408 TI - A wide diversity of Pantoea lineages are engaged in mutualistic symbiosis and cospeciation processes with stinkbugs. AB - Pantoea are emerging as widespread bacteria engaged in associations with a variety of hosts, including plants, insects and humans. Recently, mutualistic Pantoea gut symbionts have also been reported in pentatomid stinkbugs. In the present study, we examine the incidence and evolutionary history of these Pantoea symbionts in pentatomid stinkbug populations from 14 species, characterising the processes that shape their diversity. We identify midgut crypts of pentatomid stinkbugs as harboring a remarkable diversity of Pantoea. Present in 10 of the 14 sampled host species, multi-locus typing revealed the presence of 10 novel Panteoa lineages, all highly differentiated from the known Panteoa species. Rearing experiments of two pentatomid stinkbug species confirmed that these novel Panteoa are maternally inherited through egg smearing and engaged in mutualistic interactions with their hosts. Phylogenetic investigations further revealed that the Pantoea evolutionary history in pentatomid stinkbugs was notably complex: it has been shaped not only by horizontal transfers with frequent host turnover but also by strict vertical transmission over long evolutionary periods, resulting in host-symbiont codiversification. PMID- 27362410 TI - [Children and Adolescents with Asthma Differ in Lung Function Parameters and Exhaled NO from Children and Adolescents with Obesity]. AB - BACKGROUND: The prevalence of asthma and overweight/obesity in children and adolescents is continuously increasing over the last decades. It remains unclear if overweight/obesity raises the risk of developing asthma or if an uncontrolled asthma increases the risk of developing overweight/obesity by restricting physical activity. OBJECTIVES: We aimed to elucidate, if children and adolescents with overweight/obesity differ from normal-weight asthmatics in lung functions parameters (FEV1, FEV1/VC, MEF50 and SRtot) and in exhaled nitric oxide (FeNO). METHODS: Totally, n=142 children and adolescents aged 6-18 years were included in this study: group 1 comprised n=44 with overweight/obesity defined as a Body-Mass Index (BMI)>90th percentile; group 2 n=44 with a doctors diagnosed bronchial asthma according to the GINA-guidelines, and group 3 with n=36 pulmonary healthy controls. N=18 children with both asthma and overweight/obesity were excluded from further analysis. We collected data about socio-demographic variables from a standardized questionnaire, bodyplethysmography (FEV1, FEV1/VC, MEF50 and SRtot) and FeNO. RESULTS: Normal-weight children and adolescents with asthma had significantly lower FEV1/VC (Tiffenau-Index 90,9+/-12,8) and MEF50 (84.0% predicted+/-27.6) than children with overweight/obesity (97,6+/-12,4 p=0.001 respectively 99.1+/-20.9 p=0.001) and healthy controls (98+/-13,5 p=0,003; 96.7+/ 19.3 p=0.011). Normal weight asthmatics had a significantly higher FeNO (38.3 ppb) than children and adolescents with overweight/obesity (14.0 ppb p=0.014). CONCLUSIONS: Normal-weight children and adolescents with asthma differ significantly both in their lung function parameters as well as in their exhaled nitric oxide concentration from children and adolescents with overweight/obesity. For clinical practice it is important to note that children and adolescents with overweight/obesity have no signs of an obstructive airway diseases and are as resilient as healthy children and adolescents with regard to their lung function. The possible late-onset of asthma symptoms and lung function changes in children and adolescents with overweight/obesity requires further detailed longitudinal studies. PMID- 27362409 TI - A Stem Cell Strategy Identifies Glycophorin C as a Major Erythrocyte Receptor for the Rodent Malaria Parasite Plasmodium berghei. AB - The clinical complications of malaria are caused by the parasite expansion in the blood. Invasion of erythrocytes is a complex process that depends on multiple receptor-ligand interactions. Identification of host receptors is paramount for fighting the disease as it could reveal new intervention targets, but the enucleated nature of erythrocytes makes genetic approaches impossible and many receptors remain unknown. Host-parasite interactions evolve rapidly and are therefore likely to be species-specific. As a results, understanding of invasion receptors outside the major human pathogen Plasmodium falciparum is very limited. Here we use mouse embryonic stem cells (mESCs) that can be genetically engineered and differentiated into erythrocytes to identify receptors for the rodent malaria parasite Plasmodium berghei. Two proteins previously implicated in human malaria infection: glycophorin C (GYPC) and Band-3 (Slc4a1) were deleted in mESCs to generate stable cell lines, which were differentiated towards erythropoiesis. In vitro infection assays revealed that while deletion of Band-3 has no effect, absence of GYPC results in a dramatic decrease in invasion, demonstrating the crucial role of this protein for P. berghei infection. This stem cell approach offers the possibility of targeting genes that may be essential and therefore difficult to disrupt in whole organisms and has the potential to be applied to a variety of parasites in diverse host cell types. PMID- 27362411 TI - [A survey of Local Physicians and Psychotherapists on Cooperation in Regional Networks for Early Child Interventions in Saxony-Anhalt]. AB - BACKGROUND: Early childhood interventions positively contribute to health related child development. For these interventions, networks are a necessary prerequisite as they promote interdisciplinary and interprofessional cooperation. This holds especially true for the integration of health system protagonists. METHODS: In a cross-sectional survey local paediatrists, gynaecologists, general practitioners, and psychotherapists were asked about their knowledge, experiences, desires, and reservations regarding cooperation in early childhood intervention networks. RESULTS: 64 out of 1747 (3.7%) eligible clinicians answered the survey. On average they estimated that 10.1% of the families they are treating would benefit from early childhood interventions. Participants rated themselves as competent to offer appropriate early childhood interventions. The youth welfare service was judged as the most important institution for their own professional practice by 84.4%. Additionally to an applicable agenda, a fair group moderation of network meetings was seen as a substantial requirement in order to take part in network meetings. CONCLUSION: Health professionals are important protagonists in early childhood interventions. Clinicians should assess relevant problems in families and offer appropriate support on a regular basis. Alongside clearly defined regional contacts, interprofessional continuing education seems mandatory. PMID- 27362412 TI - Use and Cutaneous Side Effects of Skin Antiseptics in Extremely Low Birth Weight Infants - A Retrospective Survey of the German NICUs. AB - Background Nosocomial infections are a serious problem in the treatment of extremely low birth weight infants (ELBW, <1 000 g). In these patients, effective skin antisepsis is critical to prevent hospital-acquired infections and their sequelae. However, serious side effects of topical antiseptics have been repeatedly reported in extremely preterm infants and no agreement has been reached on the best product in this population. Therefore, we conducted a survey of the German NICUs aiming to investigate current practices and safety of topical antiseptics in ELBW neonates. METHODS: We sent anonymized questionnaires to 166 German NICUs with the highest level of care. RESULTS: Usable questionnaires were returned by 64 NICUs (39%). These NICUs had treated a total of 2130 patients with a birth weight<1 000 g in 2012. Octenidine without phenoxyethanol (OwPh) and Octenisept((r)) were the predominantly used skin antiseptics for intensive-care procedures. At least one skin complication was reported by 27% (n=17) of the NICUs. In 9 cases Octenisept((r)) was used, and in 6 cases octenidine was used. CONCLUSIONS: According to our knowledge, this is the first study surveying practices and safety of skin antisepsis in ELBWs in the German NICUs. Most German NICUs use octenidine, however, in different preparations. Skin complications including blistering, necrosis and scarring were seen with all octenidine products, a fact which has not been previously reported. PMID- 27362413 TI - The Importance of Computed Tomography for the Diagnosis Of Duodenal Perforation in a Paediatric Patient with Juvenile Dermatomyositis. PMID- 27362414 TI - Eventration of the diaphragm in a 4-year-old child diagnosed with dextrocardia. PMID- 27362415 TI - Multidrug-Resistant Bacteria in Refugee Children and Pregnant Women Admitted to a General Hospital in North Rhine-Westphalia, Germany. PMID- 27362417 TI - Lattice thermal conductivity in layered BiCuSeO. AB - We quantify the low lattice thermal conductivity in layered BiCuSeO (the oxide with the highest known figure of merit). It turns out that the scattering of acoustical into optical phonons is strongly enhanced in the material because of the special structure of the phonon dispersion. For example, at room temperature the optical phonons account for an enormous 42% of the lattice thermal conductivity. We also quantify the anisotropy of the lattice thermal conductivity and determine the distribution of the mean free path of the phonons at different temperatures to provide a guide for tuning the thermal properties. PMID- 27362416 TI - Hypermethylation of FOXP3 Promoter and Premature Aging of the Immune System in Female Patients with Panic Disorder? AB - Immunological abnormalities associated with pathological conditions, such as higher infection rates, inflammatory diseases, cancer or cardiovascular events are common in patients with panic disorder. In the present study, T cell receptor excision circles (TRECs), Forkhead-Box-Protein P3 gene (FOXP3) methylation of regulatory T cells (Tregs) and relative telomere lengths (RTLs) were investigated in a total and subsamples of 131 patients with panic disorder as compared to 131 age- and sex-matched healthy controls in order to test for a potential dysfunction and premature aging of the immune system in anxiety disorders. Significantly lower TRECs (p = 0.004) as well as significant hypermethylation of the FOXP3 promoter region (p = 0.005) were observed in female (but not in male) patients with panic disorder as compared to healthy controls. No difference in relative telomere length was discerned between patients and controls, but significantly shorter telomeres in females, smokers and older persons within the patient group. The presently observed reduced TRECs in panic disorder patients and FOXP3 hypermethylation in female patients with panic disorder potentially reflect impaired thymus and immunosuppressive Treg function, which might partly account for the known increased morbidity and mortality of anxiety disorders conferred by e.g. cancer and cardiovascular disorders. PMID- 27362418 TI - A Powerful Procedure for Pathway-Based Meta-analysis Using Summary Statistics Identifies 43 Pathways Associated with Type II Diabetes in European Populations. AB - Meta-analysis of multiple genome-wide association studies (GWAS) has become an effective approach for detecting single nucleotide polymorphism (SNP) associations with complex traits. However, it is difficult to integrate the readily accessible SNP-level summary statistics from a meta-analysis into more powerful multi-marker testing procedures, which generally require individual level genetic data. We developed a general procedure called Summary based Adaptive Rank Truncated Product (sARTP) for conducting gene and pathway meta analysis that uses only SNP-level summary statistics in combination with genotype correlation estimated from a panel of individual-level genetic data. We demonstrated the validity and power advantage of sARTP through empirical and simulated data. We conducted a comprehensive pathway-based meta-analysis with sARTP on type 2 diabetes (T2D) by integrating SNP-level summary statistics from two large studies consisting of 19,809 T2D cases and 111,181 controls with European ancestry. Among 4,713 candidate pathways from which genes in neighborhoods of 170 GWAS established T2D loci were excluded, we detected 43 T2D globally significant pathways (with Bonferroni corrected p-values < 0.05), which included the insulin signaling pathway and T2D pathway defined by KEGG, as well as the pathways defined according to specific gene expression patterns on pancreatic adenocarcinoma, hepatocellular carcinoma, and bladder carcinoma. Using summary data from 8 eastern Asian T2D GWAS with 6,952 cases and 11,865 controls, we showed 7 out of the 43 pathways identified in European populations remained to be significant in eastern Asians at the false discovery rate of 0.1. We created an R package and a web-based tool for sARTP with the capability to analyze pathways with thousands of genes and tens of thousands of SNPs. PMID- 27362420 TI - Announcement: CDC's 70th Anniversary. AB - July 1, 2016, marks the 70th anniversary of the establishment of CDC. Since the agency's launch as the Communicable Disease Center on July 1, 1946, CDC's primary mission has been improving public health in the United States and around the world through prevention and preparedness. In the seven decades since CDC's founding, the agency has grown in size and mission and is recognized as the nation's premiere health promotion, disease prevention, and emergency preparedness agency, and a global leader in public health. CDC's mission has progressed beyond communicable disease control and now encompasses noninfectious diseases, injury prevention, and environmental and occupational health. PMID- 27362419 TI - Lessons from Nature: Understanding Immunity to HCV to Guide Vaccine Design. PMID- 27362421 TI - Cost-Effectiveness of Apixaban versus Warfarin in Chinese Patients with Non Valvular Atrial Fibrillation: A Real-Life and Modelling Analyses. AB - OBJECTIVES: Many of the cost-effectiveness analyses of apixaban against warfarin focused on Western populations but Asian evidence remains less clear. The present study aims to evaluate the cost-effectiveness of apixaban against warfarin in Chinese patients with non-valvular atrial fibrillation (NVAF) from a public institutional perspective in Hong Kong. METHODS: We used a Markov model incorporating 12 health state transitions, and simulated the disease progression of NVAF in 1,000 hypothetical patients treated with apixaban/warfarin. Risks of clinical events were based on the ARISTOTLE trial and were adjusted with local International Normalized Ratio control, defined as the time in therapeutic range. Real-life input for the model, including patients' demographics and clinical profiles, post-event treatment patterns, and healthcare costs, were determined by a retrospective cohort of 40,569 incident patients retrieved from a Hong Kong wide electronic medical database. Main outcome measurements included numbers of thromboembolic and bleeding events, life years, quality-adjusted life years (QALYs) and direct healthcare cost. When comparing apixaban and warfarin, treatment with incremental cost-effectiveness ratio (ICER) less than one local GDP per capita (USD 33,534 in 2014) was defined to be cost-effective. RESULTS: In the lifetime simulation, fewer numbers of events were estimated for the apixaban group, resulting in reduced event-related direct medical costs. The estimated ICER of apixaban was USD 7,057 per QALY at base-case analysis and ranged from USD 1,061 to 14,867 per QALY under the 116 tested scenarios in deterministic sensitivity analysis. While in probabilistic sensitivity analysis, the probability of apixaban being the cost-effective alternative to warfarin was 96% and 98% at a willingness to pay threshold of USD 33,534 and 100,602 per QALY, respectively. CONCLUSIONS: Apixaban is likely to be a cost-effective alternative to warfarin for stroke prophylaxis in Chinese patients with NVAF in Hong Kong. PMID- 27362422 TI - Desorption Electrospray Ionization (DESI) Mass Spectrometric Imaging of the Distribution of Rohitukine in the Seedling of Dysoxylum binectariferum Hook. F. AB - Ambient ionization mass spectrometric imaging of all parts of the seedling of Dysoxylum binectariferum Hook. f (Meliaceae) was performed to reconstruct the molecular distribution of rohitukine (Rh) and related compounds. The species accumulates Rh, a prominent chromone alkaloid, in its seeds, fruits, and stem bark. Rh possesses anti-inflammatory, anti-cancer, and immuno-modulatory properties. Desorption electrospray ionization mass spectrometry imaging (DESI MSI) and electrospray ionization (ESI) tandem mass spectrometry (MS/MS) analysis detected Rh as well as its glycosylated, acetylated, oxidized, and methoxylated analogues. Rh was predominantly distributed in the main roots, collar region of the stem, and young leaves. In the stem and roots, Rh was primarily restricted to the cortex region. The identities of the metabolites were assigned based on both the fragmentation patterns and exact mass analyses. We discuss these results, with specific reference to the possible pathways of Rh biosynthesis and translocation during seedling development in D. binectariferum. PMID- 27362423 TI - Hydrogen Peroxide-Resistant CotA and YjqC of Bacillus altitudinis Spores Are a Promising Biocatalyst for Catalyzing Reduction of Sinapic Acid and Sinapine in Rapeseed Meal. AB - For the more efficient detoxification of phenolic compounds, a promising avenue would be to develop a multi-enzyme biocatalyst comprising peroxidase, laccase and other oxidases. However, the development of this multi-enzyme biocatalyst is limited by the vulnerability of fungal laccases and peroxidases to hydrogen peroxide (H2O2)-induced inactivation. Therefore, H2O2-resistant peroxidase and laccase should be exploited. In this study, H2O2-stable CotA and YjqC were isolated from the outer coat of Bacillus altitudinis SYBC hb4 spores. In addition to the thermal and alkali stability of catalytic activity, CotA also exhibited a much higher H2O2 tolerance than fungal laccases from Trametes versicolor and Trametes trogii. YjqC is a sporulation-related manganese (Mn) catalase with striking peroxidase activity for sinapic acid (SA) and sinapine (SNP). In contrast to the typical heme-containing peroxidases, the peroxidase activity of YjqC was also highly resistant to inhibition by H2O2 and heat. CotA could also catalyze the oxidation of SA and SNP. CotA had a much higher affinity for SA than B. subtilis CotA. CotA and YjqC rendered from B. altitudinis spores had promising laccase and peroxidase activities for SA and SNP. Specifically, the B. altitudinis spores could be regarded as a multi-enzyme biocatalyst composed of CotA and YjqC. The B. altitudinis spores were efficient for catalyzing the degradation of SA and SNP in rapeseed meal. Moreover, efficiency of the spore catalyzed degradation of SA and SNP was greatly improved by the presence of 15 mM H2O2. This effect was largely attributed to synergistic biocatalysis of the H2O2 resistant CotA and YjqC toward SA and SNP. PMID- 27362425 TI - Four-Component Reaction for the Synthesis of Dithiocarbamates Starting from Cyclic Imines. AB - An efficient one-pot, four-component reaction for the synthesis of dithiocarbamates using carbon disulfide, cyclic imines, acid chlorides, and commercially available primary or secondary amines has been developed by performing an acid chloride addition to a heterocyclic imine followed by subsequent nucleophilic substitution of in situ generated dithiocarbamic acid. With the aid of the newly developed and powerful multicomponent reaction, a direct route for the synthesis of 24 unknown dithiocarbamates in moderate to good yield under mild conditions is enabled. PMID- 27362424 TI - Low-Cost 3D Printers Enable High-Quality and Automated Sample Preparation and Molecular Detection. AB - Most molecular diagnostic assays require upfront sample preparation steps to isolate the target's nucleic acids, followed by its amplification and detection using various nucleic acid amplification techniques. Because molecular diagnostic methods are generally rather difficult to perform manually without highly trained users, automated and integrated systems are highly desirable but too costly for use at point-of-care or low-resource settings. Here, we showcase the development of a low-cost and rapid nucleic acid isolation and amplification platform by modifying entry-level 3D printers that cost between $400 and $750. Our modifications consisted of replacing the extruder with a tip-comb attachment that houses magnets to conduct magnetic particle-based nucleic acid extraction. We then programmed the 3D printer to conduct motions that can perform high-quality extraction protocols. Up to 12 samples can be processed simultaneously in under 13 minutes and the efficiency of nucleic acid isolation matches well against gold standard spin-column-based extraction technology. Additionally, we used the 3D printer's heated bed to supply heat to perform water bath-based polymerase chain reactions (PCRs). Using another attachment to hold PCR tubes, the 3D printer was programmed to automate the process of shuttling PCR tubes between water baths. By eliminating the temperature ramping needed in most commercial thermal cyclers, the run time of a 35-cycle PCR protocol was shortened by 33%. This article demonstrates that for applications in resource-limited settings, expensive nucleic acid extraction devices and thermal cyclers that are used in many central laboratories can be potentially replaced by a device modified from inexpensive entry-level 3D printers. PMID- 27362426 TI - Prostate-specific antigen and its derivatives in young adults occupationally exposed to quarry pollutants in southeastern Nigeria. AB - To evaluate the level of total prostate-specific antigen (PSA) and effect of duration of exposure to pollutants in quarry workers, 5 mls of blood sample was collected from participants: 72 male quarry workers exposed to quarry pollutants and 72 unexposed controls. PSA estimations were done using the principle of ELISA. Mean total PSA, free PSA, and free-total PSA ratio levels of quarry workers did not differ from those of controls and was below the cutoff for the risk of prostate diseases. Higher mean total PSA and free PSA were observed in workers exposed for > 3 years compared to the unexposed control and workers exposed for <= 3 years. Age-adjusted linear regression indicated significant association (R = 0.515; p < .001) between the duration of exposure and total PSA level in quarry workers. This study suggests that longer duration of exposure to the quarry pollutants may elevate PSA level if precautions are not taken to minimize dose of exposure. PMID- 27362427 TI - Refugees of the Syrian Civil War: Impact on Reemerging Infections, Health Services, and Biosecurity in Turkey. AB - After the Arab Spring uprising, Syria descended into a civil war in 2011. By March 2016, the United Nations reported that 13.5 million Syrians required humanitarian assistance, including 6.6 million internally displaced persons and more than 4.8 million refugees outside of Syria. Turkey is currently hosting the largest number of Syrian refugees-more than 2.7 million. A limited number of refugees are living in camps settled around the border, and others are spread throughout Turkey. This explosive and unexpected increase in the Syrian population in Turkey has had several negative impacts on health and social determinants. The overload of healthcare facilities has led to shortages in childhood immunization programs, drugs, and access to clean water and food supplies. According to Ministry of Health data, more than 7.5 million Syrians were examined at outpatient clinics, and 299,240 were hospitalized; most of those hospitalized were injured and wounded victims who require and have been occupying intensive care units. The refugees generally live in crowded and unsanitary conditions, which may lead to the spread of respiratory, skin, gastrointestinal, and genital system infections. Currently, measles, poliomyelitis, leishmaniasis, and multidrug-resistant tuberculosis are the reemerging infections being most frequently recorded. Multidrug-resistant gram-negative bacterial infections seem to be an increasing problem in gunshot or surgical wounds. Hepatitis A, malaria, and varicella have been seen with a high incidence among the refugees. There are many problems waiting to be resolved for health and living standards in Turkey. PMID- 27362428 TI - The Socioeconomic Factors and the Indigenous Component of Tuberculosis in Amazonas. AB - Despite the availability of tuberculosis prevention and control services throughout Amazonas, high rates of morbidity and mortality from tuberculosis remain in the region. Knowledge of the social determinants of tuberculosis in Amazonas is important for the establishment of public policies and the planning of effective preventive and control measures for the disease. To analyze the relationship of the spatial distribution of the incidence of tuberculosis in municipalities and regions of Amazonas to the socioeconomic factors and indigenous tuberculosis component, from 2007 to 2013. An ecological study was conducted based on secondary data from the epidemiological surveillance of tuberculosis. A linear regression model was used to analyze the relationship of the annual incidence of tuberculosis to the socioeconomic factors, performance indicators of health services, and indigenous tuberculosis component. The distribution of the incidence of tuberculosis in the municipalities of Amazonas was positively associated with the Gini index and the population attributable fraction of tuberculosis in the indigenous peoples, but negatively associated with the proportion of the poor and the unemployment rate. The spatial distribution of tuberculosis in the different regions of Amazonas was heterogeneous and closely related with the socioeconomic factors and indigenous component of tuberculosis. PMID- 27362429 TI - Characterization of ZnO Interlayers for Organic Solar Cells: Correlation of Electrochemical Properties with Thin-Film Morphology and Device Performance. AB - This report focuses on the evaluation of the electrochemical properties of both solution-deposited sol-gel (sg-ZnO) and sputtered (sp-ZnO) zinc oxide thin films, intended for use as electron-collecting interlayers in organic solar cells (OPVs). In the electrochemical studies (voltammetric and impedance studies), we used indium-tin oxide (ITO) over coated with either sg-ZnO or sp-ZnO interlayers, in contact with either plain electrolyte solutions, or solutions with probe redox couples. The electroactive area of exposed ITO under the ZnO interlayer was estimated by characterizing the electrochemical response of just the oxide interlayer and the charge transfer resistance from solutions with the probe redox couples. Compared to bare ITO, the effective electroactive area of ITO under sg ZnO films was ca. 70%, 10%, and 0.3% for 40, 80, and 120 nm sg-ZnO films. More compact sp-ZnO films required only 30 nm thicknesses to achieve an effective electroactive ITO area of ca. 0.02%. We also examined the electrochemical responses of these same ITO/ZnO heterojunctions overcoated with device thickness pure poly(3-hexylthiophehe) (P3HT), and donor/acceptor blended active layers (P3HT:PCBM). Voltammetric oxidation/reduction of pure P3HT thin films on ZnO/ITO contacts showed that pinhole pathways exist in ZnO films that permit dark oxidation (ITO hole injection into P3HT). In P3HT:PCBM active layers, however, the electrochemical activity for P3HT oxidation is greatly attenuated, suggesting PCBM enrichment near the ZnO interface, effectively blocking P3HT interaction with the ITO contact. The shunt resistance, obtained from dark current-voltage behavior in full P3HT/PCBM OPVs, was dependent on both (i) the porosity of the sg ZnO or sp-ZnO films (as revealed by probe molecule electrochemistry) and (ii) the apparent enrichment of PCBM at ZnO/P3HT:PCBM interfaces, both effects conveniently revealed by electrochemical characterization. We anticipate that these approaches will be applicable to a wider array of solution-processed interlayers for "printable" solar cells. PMID- 27362430 TI - In situ TEM visualization of superior nanomechanical flexibility of shear exfoliated phosphorene. AB - Recently discovered atomically thin black phosphorus (called phosphorene) holds great promise for applications in flexible nanoelectronic devices. Experimentally identifying and characterizing nanomechanical properties of phosphorene are challenging, but also potentially rewarding. This work combines for the first time in situ transmission electron microscopy (TEM) imaging and an in situ micro manipulation system to directly visualize the nanomechanical behaviour of individual phosphorene nanoflakes. We demonstrate that the phosphorene nanoflakes can be easily bent, scrolled, and stretched, showing remarkable mechanical flexibility rather than fracturing. An out-of-plane plate-like bending mechanism and in-plane tensile strain of up to 34% were observed. Moreover, a facile liquid phase shear exfoliation route has been developed to produce such mono-layer and few-layer phosphorene nanoflakes in organic solvents using only a household kitchen blender. The effects of surface tensions of the applied solvents on the ratio of average length and thickness (L/T) of the nanoflakes were studied systematically. The results reported here will pave the way for potential industrial-scale applications of flexible phosphorene nanoelectronic devices. PMID- 27362431 TI - How to Direct the Edges of the Connectomes: Dynamics of the Consensus Connectomes and the Development of the Connections in the Human Brain. AB - The human braingraph or the connectome is the object of an intensive research today. The advantage of the graph-approach to brain science is that the rich structures, algorithms and definitions of graph theory can be applied to the anatomical networks of the connections of the human brain. In these graphs, the vertices correspond to the small (1-1.5 cm2) areas of the gray matter, and two vertices are connected by an edge, if a diffusion-MRI based workflow finds fibers of axons, running between those small gray matter areas in the white matter of the brain. One main question of the field today is discovering the directions of the connections between the small gray matter areas. In a previous work we have reported the construction of the Budapest Reference Connectome Server http://connectome.pitgroup.org from the data recorded in the Human Connectome Project of the NIH. The server generates the consensus braingraph of 96 subjects in Version 2, and of 418 subjects in Version 3, according to selectable parameters. After the Budapest Reference Connectome Server had been published, we recognized a surprising and unforeseen property of the server. The server can generate the braingraph of connections that are present in at least k graphs out of the 418, for any value of k = 1, 2, ..., 418. When the value of k is changed from k = 418 through 1 by moving a slider at the webserver from right to left, certainly more and more edges appear in the consensus graph. The astonishing observation is that the appearance of the new edges is not random: it is similar to a growing shrub. We refer to this phenomenon as the Consensus Connectome Dynamics. We hypothesize that this movement of the slider in the webserver may copy the development of the connections in the human brain in the following sense: the connections that are present in all subjects are the oldest ones, and those that are present only in a decreasing fraction of the subjects are gradually the newer connections in the individual brain development. An animation on the phenomenon is available at https://youtu.be/yxlyudPaVUE. Based on this observation and the related hypothesis, we can assign directions to some of the edges of the connectome as follows: Let Gk + 1 denote the consensus connectome where each edge is present in at least k+1 graphs, and let Gk denote the consensus connectome where each edge is present in at least k graphs. Suppose that vertex v is not connected to any other vertices in Gk+1, and becomes connected to a vertex u in Gk, where u was connected to other vertices already in Gk+1. Then we direct this (v, u) edge from v to u. PMID- 27362432 TI - Spatial Control of Cell-Nanosurface Interactions by Tantalum Oxide Nanodots for Improved Implant Geometry. AB - Nanotopological cues can be exploited to understand the nature of interactions between cells and their microenvironment to generate superior implant geometries. Nanosurface parameters which modulate the cell behavior and characteristics such as focal adhesions, cell morphology are not clearly understood. Here, we studied the role of different nanotopographic dimensions in modulating the cell behavior, characteristics and ultimately the cell fate and accordingly, a methodology to improve implant surface geometry is proposed. Tantalum oxide nanodots of 50, 100nm dot diameter with an inter-dot spacing of 20, 70nm and heights 40, 100nm respectively, were engineered on Silicon substrates. MG63 cells were cultured for 72 hours and the modulation in morphology, focal adhesions, cell extensible area, cell viability, transcription factors and genes responsible for bone protein secretion as a function of the nanodot diameter, inter-dot distance and nanodot height were evaluated. Nanodots of 50nm diameter with a 20nm inter-dot spacing and 40nm height enhanced cell spreading area by 40%, promoted cell viability by 70% and upregulated transcription factors and genes twice as much, as compared to the 100nm nanodots with 70nm inter-dot spacing and 100nm height. Favorable interactions between cells and all dimensions of 50nm nanodot diameter were observed, determined with Scanning electron microscopy and Immunofluorescence staining. Nanodot height played a vital role in controlling the cell fate. Dimensions of nanodot features which triggered a transition in cell characteristics or behavior was also defined through statistical analysis. The findings of this study provide insights in the parameters of nanotopographic features which can vitally control the cell fate and should therefore be taken into account when designing implant geometries. PMID- 27362435 TI - High-Performance Ru1 /CeO2 Single-Atom Catalyst for CO Oxidation: A Computational Exploration. AB - By means of density functional theory computations, we examine the stability and CO oxidation activity of single Ru on CeO2 (111), TiO2 (110) and Al2 O3 (001) surfaces. The heterogeneous system Ru1 /CeO2 has very high stability, as indicated by the strong binding energies and high diffusion barriers of a single Ru atom on the ceria support, while the Ru atom is rather mobile on TiO2 (110) and Al2 O3 (001) surfaces and tends to form clusters, excluding these systems from having a high efficiency per Ru atom. The Ru1 /CeO2 exhibits good catalytic activity for CO oxidation via the Langmuir-Hinshelwood mechanism, thus is a promising single-atom catalyst. PMID- 27362433 TI - Establishment of Nephrin Reporter Mice and Use for Chemical Screening. AB - Nephrin is a critical component of glomerular filtration barrier, which is important to maintain glomerular structure and avoid proteinuria. Downregulation of nephrin expression is commonly observed at early stage of glomerular disorders, suggesting that methods to increase nephrin expression in podocytes may have therapeutic utility. Here, we generated a knockin mouse line carrying single copy of 5.5 kb nephrin promoter controlling expression of enhanced green fluorescent protein (EGFP) at Rosa26 genomic locus (Nephrin-EGFP mouse). In these mice, EGFP was specifically expressed in podocytes. Next, we isolated and cultivated glomeruli from these mice, and developed a protocol to automatically quantitate EGFP expression in cultured glomeruli. EGFP signal was markedly reduced after 5 days of culture but reduction was inhibited by vitamin D treatment. We confirmed that vitamin D increased mRNA and protein expression of endogenous nephrin in cultivated glomeruli. Thus, we generated a mouse line converting nephrin promoter activity into fluorescence, which can be used to screen compounds having activity to enhance nephrin gene expression. PMID- 27362436 TI - Studies on cerebral protection of digoxin against hypoxic-ischemic brain damage in neonatal rats. AB - Hypoxic-ischemic brain damage (HIBD) is a major cause of neonatal acute deaths and chronic nervous system damage. Our present study was designed to investigate the possible neuroprotective effect of digoxin-induced pharmacological preconditioning after hypoxia-ischemia and underlying mechanisms. Neonatal rats were assigned randomly to control, HIBD, or HIBD+digoxin groups. Pharmacological preconditioning was induced by administration of digoxin 72 h before inducing HIBD by carotid occlusion+hypoxia. Behavioral assays, and neuropathological and apoptotic assessments were performed to examine the effects; the expression of Na/K ATPase was also assessed. Rats in the HIBD group showed deficiencies on the T-maze, radial water maze, and postural reflex tests, whereas the HIBD+digoxin group showed significant improvements on all behavioral tests. The rats treated with digoxin showed recovery of pathological conditions, increased number of neural cells and proliferative cells, and decreased number of apoptotic cells. Meanwhile, an increased expression level of Na/K ATPase was observed after digoxin preconditioning treatment. The preconditioning treatment of digoxin contributed toward an improved functional recovery and exerted a marked neuroprotective effect including promotion of cell proliferation and reduction of apoptosis after HIBD, and the neuroprotective action was likely associated with increased expression of Na/K ATPase. PMID- 27362437 TI - Correlation between astrocyte activity and recovery from blood-brain barrier breakdown caused by brain injury. AB - Glial activation is associated with cell proliferation and upregulation of astrocyte marker expression following traumatic injury in the brain. However, the biological significance of these processes remains unclear. In the present study, astrocyte activation was investigated in a murine brain injury model. Brain injury induces blood-brain barrier (BBB) breakdown and immunoglobulin G (IgG) leak into the brain parenchyma. The recovery of BBB breakdown was evaluated by analyzing immunofluorescent staining with mouse IgG antibody. IgG leakage was greatest at 1 day after stab wound injury and decreased thereafter, and almost diminished after 7 days. Bromodeoxy uridine incorporation was used, and astrocyte proliferation rates were examined by coimmunostaining with anti-bromodeoxy uridine and anti-glial fibrillary acid protein antibodies. Consistent with IgG leakage assays, astrocyte activation was the highest at day 3 and decreased after 7 days. Moreover, in reverse transcriptase-quantitative-PCR experiments, genes associated with BBB integrity were downregulated immediately after BBB breakdown and recovered to basal expression levels within 7 days. These data indicated that astrocyte activation correlated with BBB recovery from breakdown following brain injury. PMID- 27362438 TI - A Survey of Speech-Language-Hearing Therapists' Career Situation and Challenges in Mainland China. AB - AIMS: The aim of this survey was to investigate the background of speech-language pathologists and their training needs to provide a profile of the current state of the profession in Mainland China. METHODS: A survey was conducted of 293 speech-language therapists. The questionnaire used asked questions related to their career background and had a 24-item ranking scale covering almost all of the common speech-language-hearing disorders. A summary of the raw data was constructed by calculating the average ranking score for each answer choice in order to determine the academic training needs with the highest preference among the respondents. RESULTS: The majority of respondents were female, <35 years old and with a total service time of <5 years. More than three quarters of the training needs with the highest preference among the 24 items involved basic level knowledge of common speech-language-hearing disorders, such as diagnosis, assessment and conventional treatment, but seldom specific advanced technology or current progress. CONCLUSION: The results revealed that speech-language therapists in Mainland China tend to be young, with little total working experience and at the first stage of their career. This may be due to the lack of systematic educational programs and national certification systems for speech language therapists. PMID- 27362439 TI - Immunofluorescence staining with an antipromyelocytic leukemia antibody for a rapid diagnosis of acute promyelocytic leukemia. PMID- 27362440 TI - Which patients with epilepsy are at risk for psychogenic nonepileptic seizures (PNES)? A multicenter case-control study. AB - OBJECTIVE: We sought to examine the clinical and electrographic differences between patients with combined epileptic (ES) and psychogenic nonepileptic seizures (PNES) and age- and gender-matched patients with ES-only and PNES-only. METHODS: Data from 138 patients (105 women [77%]), including 46 with PNES/ES (39+/-12years), 46 with PNES-only (39+/-11years), and 46 with ES-only (39+/ 11years), were compared using logistic regression analysis after adjusting for clustering effect. RESULTS: In the cohort with PNES/ES, ES antedated PNES in 28 patients (70%) and occurred simultaneously in 11 (27.5%), while PNES were the initial presentation in only 1 case (2.5%); disease duration was undetermined in 6. Compared with those with ES-only, patients with PNES/ES had higher depression and anxiety scores, shorter-duration electrographic seizures, less ES absence/staring semiology (all p<=0.01), and more ES arising in the right hemisphere, both in isolation and in combination with contralateral brain regions (61% vs. 41%; p=0.024, adjusted for anxiety and depression) and tended to have less ES arising in the left temporal lobe (13% vs. 28%; p=0.054). Compared with those with PNES-only, patients with PNES/ES tended to show fewer right-hemibody PNES events (7% vs. 23%; p=0.054) and more myoclonic semiology (10% vs. 2%; p=0.073). CONCLUSIONS: Right-hemispheric electrographic seizures may be more common among patients with ES who develop comorbid PNES, in agreement with prior neurobiological studies on functional neurological disorders. PMID- 27362441 TI - Tuning One-Dimensional Nanostructures of Bola-Like Peptide Amphiphiles by Varying the Hydrophilic Amino Acids. AB - By combining experimental measurements and computer simulations, we here show that for the bola-like peptide amphiphiles XI4 X, where X=K, R, and H, the hydrophilic amino acid substitutions have little effect on the beta-sheet hydrogen-bonding between peptide backbones. Whereas all of the peptides self assemble into one dimensional (1D) nanostructures with completely different morphologies, that is, nanotubes and helical nanoribbons for KI4 K, flat and multilayered nanoribbons for HI4 H, and twisted and bilayered nanoribbons for RI4 R. These different 1D morphologies can be explained by the distinct stacking degrees and modes of the three peptide beta-sheets along the x-direction (width) and the z-direction (height), which microscopically originate from the hydrogen bonding ability of the sheets to solvent molecules and the pairing of hydrophilic amino acid side chains between beta-sheet monolayers through stacking interactions and hydrogen bonding. These different 1D nanostructures have distinct surface chemistry and functions, with great potential in various applications exploiting the respective properties of these hydrophilic amino acids. PMID- 27362442 TI - Clinical Safety of a High Dose of Phycocyanin-Enriched Aqueous Extract from Arthrospira (Spirulina) platensis: Results from a Randomized, Double-Blind, Placebo-Controlled Study with a Focus on Anticoagulant Activity and Platelet Activation. AB - The goal for this study was to evaluate safety regarding anticoagulant activity and platelet activation during daily consumption of an aqueous cyanophyta extract (ACE), containing a high dose of phycocyanin. Using a randomized, double-blind, placebo-controlled study design, 24 men and women were enrolled after informed consent, and consumed either ACE (2.3 g/day) or placebo daily for 2 weeks. The ACE dose was equivalent to ~1 g phycocyanin per day, chosen based on the highest dose Generally Recognized as Safe (GRAS) by the U.S. Food and Drug Administration. Consuming ACE did not alter markers for platelet activation (P selectin expression) or serum P-selectin levels. No changes were seen for activated partial thromboplastin time, thrombin clotting time, or fibrinogen activity. Serum levels of aspartate transaminase (AST) showed a significant reduction after 2 weeks of ACE consumption (P < .001), in contrast to placebo where no changes were seen; the difference in AST levels between the two groups was significant at 2 weeks (P < .02). Reduced levels of alanine transaminase (ALT) were also seen in the group consuming ACE (P < .08). Previous studies showed reduction of chronic pain when consuming 1 g ACE per day. The higher dose of 2.3 g/day in this study was associated with significant reduction of chronic pain at rest and when physically active (P < .05). Consumption of ACE showed safety regarding markers pertaining to anticoagulant activity and platelet activation status, in conjunction with rapid and robust relief of chronic pain. Reduction in AST and ALT suggested improvement in liver function and metabolism. PMID- 27362443 TI - Dietary Inflammatory Index and Risk of Multiple Sclerosis in a Case-Control Study from Iran. AB - BACKGROUND: Diet and inflammation have been suggested to be important risk factors for multiple sclerosis (MS). OBJECTIVES: In this study, we examined the ability of the dietary inflammatory index (DII) to predict MS in a case-control study conducted in Iran. METHODS: This study included 68 MS cases and 140 controls hospitalized for acute non-neoplastic diseases. The DII was computed based on dietary intake assessed by a previously validated food frequency questionnaire. Logistic regression models were used to estimate ORs adjusted for age, energy, sex, body mass index, season of birth, rubella history, history of routine exercise before MS, smoking and history of consumption of cow's milk in the first 2 years of life. RESULTS: Subjects with higher DII scores (i.e., with a more pro-inflammatory diet) had a higher risk of MS, with the DII being used both as a continuous variable (ORcontinuous 1.66; 95% CI 1.19-2.31; 1 unit increase corresponding to ~15% of its range in the current study) and a categorical variable (ORDII (>1.43 vs.<=1.43) 2.68; 95% CI 1.15-6.26). CONCLUSIONS: These results indicate that a pro-inflammatory diet is associated with increased risk of MS. PMID- 27362444 TI - Molecular spectrum of TSHbeta subunit gene defects in central hypothyroidism in the UK and Ireland. AB - OBJECTIVE: Homozygous mutations in the TSH beta subunit gene (TSHB) result in severe, isolated, central congenital hypothyroidism (CCH). This entity evades diagnosis in TSH-based congenital hypothyroidism (CH) screening programmes in the UK and Ireland. Accordingly, genetic diagnosis, enabling ascertainment of affected relatives in families, is critical for prompt diagnosis and treatment of the disorder. DESIGN, PATIENTS AND MEASUREMENTS: Four cases of isolated TSH deficiency from three unrelated families in the UK and Ireland were investigated for mutations or deletions in TSHB. Haplotype analysis, to investigate a founder effect, was undertaken in cases with identical mutations (c.373delT). RESULTS: Two siblings in kindred 1 were homozygous for a previously described TSHB mutation (c.373delT). In kindreds 2 and 3, the affected individuals were compound heterozygous for TSHB c.373delT and either a 5.4-kB TSHB deletion (kindred 2, c.1 4389_417*195delinsCTCA) or a novel TSHB missense mutation (kindred 3, c.2T>C, p.Met1?). Neurodevelopmental retardation, following delayed diagnosis and treatment, was present in 3 cases. In contrast, the younger sibling in kindred 1 developed normally following genetic diagnosis and treatment from birth. CONCLUSIONS: This study, including the identification of a second, novel, TSHB deletion, expands the molecular spectrum of TSHB defects and suggests that allele loss may be a commoner basis for TSH deficiency than previously suspected. Delayed diagnosis and treatment of profound central hypothyroidism in such cases result in neurodevelopmental retardation. Inclusion of thyroxine (T4) plus thyroxine-binding globulin (TBG), or free thyroxine (FT4) in CH screening, together with genetic case ascertainment enabling earlier therapeutic intervention, could prevent such adverse sequelae. PMID- 27362445 TI - A review of practical tools for rapid monitoring of membrane bioreactors. AB - The production of high quality effluent from membrane bioreactors (MBRs) arguably requires less supervision than conventional activated sludge (CAS) processes. Nevertheless, the use of membranes brings additional issues of activated sludge filterability, cake layer formation and membrane fouling. From a practical standpoint, process engineers and operators require simple tools which offer timely information about the biological health and filterability of the mixed liquor as well as risks of membrane fouling. To this end, a range of analytical tools and biological assays are critically reviewed from this perspective. This review recommends that Capillary Suction Time (CST) analysis along with Total Suspended and Volatile Solids (TSS/VSS) analysis is used daily. For broad characterisation, total carbon and nitrogen analysis offer significant advantages over the commonly used chemical and biological oxygen demand (COD/BOD) analyses. Of the technologies for determining the vitality of the microbial biomass the most robust and reproducible, are the second generation adenosine-5'-triphosphate (ATP) test kits. Extracellular polymer concentrations are best monitored by measurement of turbidity after centrifugation. Taken collectively these tools can be used routinely to ensure timely intervention and smoother operation of MBR systems. PMID- 27362446 TI - Efficacy of water treatment processes and endemic gastrointestinal illness - A multi-city study in Sweden. AB - Outbreaks of acute gastrointestinal illnesses (AGI) have been linked to insufficient drinking water treatment on numerous occasions in the industrialized world, but it is largely unknown to what extent public drinking water influences the endemic level of AGI. This paper aimed to examine endemic AGI and the relationship with pathogen elimination efficacy in public drinking water treatment processes. For this reason, time series data of all telephone calls to the Swedish National Healthcare Guide between November 2007 and February 2014 from twenty Swedish cities were obtained. Calls concerning vomiting, diarrhea or abdominal pain (AGI calls) were separated from other concerns (non-AGI calls). Information on which type of microbial barriers each drinking water treatment plant in these cities have been used were obtained, together with the barriers' theoretical pathogen log reduction efficacy. The total log reduction in the drinking water plants varied between 0.0 and 6.1 units for viruses, 0.0-14.6 units for bacteria and 0.0-7.3 units regarding protozoans. To achieve one general efficacy parameter for each plant, a weighted mean value of the log reductions (WLR) was calculated, with the weights based on how commonly these pathogen groups cause AGI. The WLR in the plants varied between 0.0 and 6.4 units. The effect of different pathogen elimination efficacy on levels of AGI calls relative non-AGI calls was evaluated in regression models, controlling for long term trends, population size, age distribution, and climatological area. Populations receiving drinking water produced with higher total log reduction was associated with a lower relative number of AGI calls. In overall, AGI calls decreased by 4% (OR = 0.96, CI: 0.96-0.97) for each unit increase in the WLR. The findings apply to both groundwater and surface water study sites, but are particularly evident among surface water sites during seasons when viruses are the main cause of AGI. This study proposes that the endemic level of gastroenteritis can indeed be reduced with more advanced treatment processes at many municipal drinking water treatment plants. PMID- 27362447 TI - Why do residential recycled water schemes fail? A comprehensive review of risk factors and impact on objectives. AB - In Australia, recycled water schemes have been implemented in residential developments to contribute to sustainable urban development, improve water supply security and reduce pollutant discharges to the environment. A proportion of these schemes, however, have been decommissioned well before the end of their design life which raises questions about the adequacy of the risk assessment and management practices adopted for recycled water schemes. Through a detailed literature review, an investigation of 21 residential recycled water schemes and in-depth interviews with nine scheme stakeholders, we identified 34 risk factors arising from six sources which have the potential to impact the long-term viability of residential recycled water schemes. Of the 34 risk factors identified, 17 were reported to have occurred during the development and implementation of the 21 schemes investigated. The overall risk rating of the 17 factors was qualitatively defined on the basis of the likelihood of occurrence and the impact of the risk factors on the scheme objectives. The outcomes of the assessment indicate that the critical risks to the long-term viability of residential recycled water schemes are 1. unanticipated operational costs, 2. legal and contractual arrangements, 3. regulatory requirements and approval process and 4. customer complaints and expectations not met. To date, public health risks associated with the provision of recycled water have been of primary concern, though the outcomes of this study indicate that the impact to public health has been low. Evidently there is a need for improved assessment and management practices which address the range of critical risk factors, in addition to the routine consideration of public health risks. PMID- 27362448 TI - Cancer disclosure-account from a pediatric oncology ward in Egypt. AB - OBJECTIVE: Informing the child about his/her diagnosis and treatment plan is essential; research has shown that it is related to the patient's quality of life and adherence to medication. METHODS: For 7 months during 2008 (February to September), 2 study-specific questionnaires were constructed and administered to 304 parents of children diagnosed with cancer at the Children's Cancer Hospital Egypt. RESULTS: Among the 313 eligible parents of children diagnosed with cancer, 304 (97%) answered the first questionnaire and 281 (92%) answered the second questionnaire. We found that nearly three-quarters (72%) of the parents had their child's cancer diagnosis communicated by the physician. Among the 72%, the rate of the children present with the parent or parents during the disease disclosure conversation was 39% (n = 85/219). The majority of the children were in the age group 5-18 years (55%). CONCLUSIONS: Our findings indicate that cancer disclosure at the Children's Cancer Hospital is to a certain degree common; yet even when disclosure does take place, it is mainly in the absence of the child. Moreover, the information provided during the conversation may not be fully comprehended by the parent or the child because of the physician's misleading use of terms when disclosing the disease. Therefore, better practice should be developed for disease disclosure, and proper communication should be established between the patients and the provider; patient autonomy should also have an influence in the clinical practice. PMID- 27362449 TI - Sickle cell disease related internet activity is three times less frequent than cystic fibrosis related internet activity. PMID- 27362450 TI - Advancing the Economic Assessment of Microinvasive Glaucoma Surgery. PMID- 27362451 TI - Response to "Advancing the Economic Assessment of Microinvasive Glaucoma Surgery". PMID- 27362452 TI - Effect of extremely low frequency electromagnetic field on brain histopathology of Caspian Sea Cyprinus carpio. AB - There is limited research on the effect of electromagnetic field on aquatic organisms, especially freshwater fish species. This study was conducted to evaluate the effect of extremely low frequency electromagnetic field (ELF-EMF) (50 Hz) exposure on brain histopathology of Cyprinus carpio, one of the important species of Caspian Sea with significant economic value. A total of 200 healthy fish were used in this study. They were classified randomly in two groups: sham exposed group and experimental group, which were exposed to five different magnetic field intensities (0.1, 1, 3, 5, and 7 mT) at two different exposure times (0.5 and 1 h). Histologic results indicate that exposure of C. carpio to artificial ELF-EMF caused severe histopathological changes in the brain at field intensities >=3 mT leading to brain necrosis. Field intensity and duration of exposure were key parameters in induction of lesion in the brain. Further studies are needed to elucidate exact mechanism of EMF exposure on the brain. PMID- 27362453 TI - Significant Interference in Mass Cytometry from Medicinal Iodine in Human Lung. PMID- 27362455 TI - Echocardiography as an indication of continuous-time cardiac quiescence. AB - Cardiac computed tomography (CT) angiography using prospective gating requires that data be acquired during intervals of minimal cardiac motion to obtain diagnostic images of the coronary vessels free of motion artifacts. This work is intended to assess B-mode echocardiography as a continuous-time indication of these quiescent periods to determine if echocardiography can be used as a cost efficient, non-ionizing modality to develop new prospective gating techniques for cardiac CT. These new prospective gating approaches will not be based on echocardiography itself but on CT-compatible modalities derived from the mechanics of the heart (e.g. seismocardiography and impedance cardiography), unlike the current standard electrocardiogram. To this end, echocardiography and retrospectively-gated CT data were obtained from ten patients with varied cardiac conditions. CT reconstructions were made throughout the cardiac cycle. Motion of the interventricular septum (IVS) was calculated from both echocardiography and CT reconstructions using correlation-based, deviation techniques. The IVS was chosen because it (1) is visible in echocardiography images, whereas the coronary vessels generally are not, and (2) has been shown to be a suitable indicator of cardiac quiescence. Quiescent phases were calculated as the minima of IVS motion and CT volumes were reconstructed for these phases. The diagnostic quality of the CT reconstructions from phases calculated from echocardiography and CT data was graded on a four-point Likert scale by a board-certified radiologist fellowship trained in cardiothoracic radiology. Using a Wilcoxon signed-rank test, no significant difference in the diagnostic quality of the coronary vessels was found between CT volumes reconstructed from echocardiography- and CT-selected phases. Additionally, there was a correlation of 0.956 between the echocardiography- and CT-selected phases. This initial work suggests that B-mode echocardiography can be used as a tool to develop CT-compatible gating techniques based on modalities derived from cardiac mechanics rather than relying on the ECG alone. PMID- 27362456 TI - Reversal of Dabigatran with Idarucizumab. AB - INTRODUCTION: The use of novel oral anticoagulants such as dabigatran has been increasing over the last five years. Indicated for use in the prevention of thromboembolic complications from non-valvular atrial fibrillation and for the treatment and prevention of venous thromboembolic disease, dabigatran is increasingly encountered clinically. Lack of an efficacious reversal agent has been a challenge for increased clinical 10 adoption, and for management of patients with bleeding complications while taking dabigatran, or those requiring urgent procedures while taking dabigatran. Idarucizumab, a monoclonal antibody fragment, has recently been approved for use to reverse anticoagulation with dabigatran in patients with serious bleeding. AREAS COVERED: Herein we discuss the development and early clinical data evaluating the use of idarucizumab for dabigatran reversal. Expert commentary: Idarucizumab has been shown to be an efficacious reversal agent for patients receiving dabigatran. The drug provides a novel and clinically useful agent for patients with significant bleeding while receiving dabigatran, or those needing urgent invasive procedures. PMID- 27362457 TI - Monitoring of cholesterol oxidation in a lipid bilayer membrane using streptolysin O as a sensing and signal transduction element. AB - Streptolysin O (SLO), which recognizes sterols and forms nanopores in lipid membranes, is proposed as a sensing element for monitoring cholesterol oxidation in a lipid bilayer. The structural requirements of eight sterols for forming nanopores by SLO confirmed that a free 3-OH group in the beta-configuration of sterols is required for recognition by SLO in a lipid bilayer. The extent of nanopore formation by SLO in lipid bilayers increased in the order of cholestanol ~100 G. That T1m?tau is consistent with earlier success with polarization transfer from (1)H to (13)C by LFTM. PMID- 27362504 TI - Role of Corticotropin Releasing Factor 1 Signaling in Cocaine Seeking during Early Extinction in Female and Male Rats. AB - Locus coeruleus norepinephrine (LC-NE) and corticotropin releasing factor (CRF) neurons are involved in stress responses, including stress's ability to drive drug relapse. Previous animal studies indicate that female rats exhibit greater drug seeking than male rats during initial drug abstinence. Moreover, females are more sensitive to the effect of stress to drive drug seeking than males. Finally, LC-NE neurons are more sensitive to CRF in females compared to males. We hypothesized that increased drug seeking in females on extinction day one (ED1) is due to increased response to the stress of early withdrawal and is dependent upon the increased response of LC in females to CRF. We predicted that LC-NE neurons would exhibit Fos activation on ED1, and that blocking CRF1 signaling would decrease drug seeking on ED1 measured by responding on an active lever previously associated with cocaine self- administration. After chronic cocaine self-administration, female and male rats underwent a test for initial extinction responding by measuring lever pressing in the absence of cocaine. Prior to this Extinction Day 1 (ED1) session, rats were injected with vehicle or the selective CRF1 antagonist (CP) to measure effects of CRF antagonism on drug seeking during early abstinence. ED1 increased corticosterone in female rats, in proportion to lever responding in male and female, indicating that ED1 was stressful. Pretreatment with CP decreased cocaine seeking on ED1 more effectively in female compared to male rats. This increase in responding was associated with an increase in activation of LC NE neurons. Together, these findings indicate that stress, and signaling at CRF receptors in LC, may be involved in the increased drug seeking during initial abstinence. PMID- 27362508 TI - Antidepressant Treatment for Postnatal Depression. PMID- 27362506 TI - Prenatal DHA supplementation and infant attention. AB - BACKGROUND: Results of randomized trials on the effects of prenatal docosahexaenoic acid (DHA) on infant cognition are mixed, but most trials have used global standardized outcomes, which may not be sensitive to effects of DHA on specific cognitive domains. METHODS: Women were randomized to 600 mg/d DHA or a placebo for the last two trimesters of pregnancy. Infants of these mothers were then followed on tests of visual habituation at 4, 6, and 9 mo of age. RESULTS: DHA supplementation did not affect look duration or habituation parameters but infants of supplemented mothers maintained high levels of sustained attention (SA) across the first year; SA declined for the placebo group. The supplemented group also showed significantly reduced attrition on habituation tasks, especially at 6 and 9 mo. CONCLUSION: The findings support with the suggestion that prenatal DHA may positively affect infants' attention and regulation of state. PMID- 27362507 TI - Integration of AI-2 Based Cell-Cell Signaling with Metabolic Cues in Escherichia coli. AB - The quorum sensing molecule Autoinducer-2 (AI-2) is generated as a byproduct of activated methyl cycle by the action of LuxS in Escherichia coli. AI-2 is synthesized, released and later internalized in a cell-density dependent manner. Here, by mutational analysis of the genes, uvrY and csrA, we describe a regulatory circuit of accumulation and uptake of AI-2. We constructed a single copy chromosomal luxS-lacZ fusion in a luxS + merodiploid strain and evaluated its relative expression in uvrY and csrA mutants. At the entry of stationary phase, the expression of the fusion and AI-2 accumulation was positively regulated by uvrY and negatively regulated by csrA respectively. A deletion of csrA altered message stability of the luxS transcript and CsrA protein exhibited weak binding to 5' luxS regulatory region. DNA protein interaction and chromatin immunoprecipitation analysis confirmed direct interaction of UvrY with the luxS promoter. Additionally, reduced expression of the fusion in hfq deletion mutant suggested involvement of small RNA interactions in luxS regulation. In contrast, the expression of lsrA operon involved in AI-2 uptake, is negatively regulated by uvrY and positively by csrA in a cell-density dependent manner. The dual role of csrA in AI-2 synthesis and uptake suggested a regulatory crosstalk of cell signaling with carbon regulation in Escherichia coli. We found that the cAMP-CRP mediated catabolite repression of luxS expression was uvrY dependent. This study suggests that luxS expression is complex and regulated at the level of transcription and translation. The multifactorial regulation supports the notion that cell-cell communication requires interaction and integration of multiple metabolic signals. PMID- 27362510 TI - Mechanistic insights into the distribution of carbohydrate clusters on cell membranes revealed by dSTORM imaging. AB - Cell surface carbohydrates play significant roles in many physiological processes and act as primary markers to indicate various cellular physiological states. The functions of carbohydrates are always associated with their expression and distribution on cell membranes. Based on our previous work, we found that carbohydrates tend to form clusters; however, the underlying mechanism of these clusters remains unknown. Through the direct stochastic optical reconstruction microscopy (dSTORM) strategy, we found that with the contributions of lipid raft as a stable factor and actin cytoskeleton as a restrictive factor, carbohydrate clusters can stably exist with restricted size. Additionally, we revealed that the formation of most carbohydrate clusters (Gal and GlcANc clusters) depended on the carbohydrate-binding proteins (i.e., galectins) cross-linking their specific carbohydrate ligands. Our results clarify the organizational mechanism of carbohydrates on cell surfaces from their formation, stable existence and size restriction, which promotes a better understanding of the relationship between the function and distribution of carbohydrates, as well as the structure of cell membranes. PMID- 27362511 TI - Health Communication Research for Nursing Science and Practice. PMID- 27362509 TI - Roles of C-Terminal Region of Yeast and Human Rad52 in Rad51-Nucleoprotein Filament Formation and ssDNA Annealing. AB - Yeast Rad52 (yRad52) has two important functions at homologous DNA recombination (HR); annealing complementary single-strand DNA (ssDNA) molecules and recruiting Rad51 recombinase onto ssDNA (recombination mediator activity). Its human homolog (hRAD52) has a lesser role in HR, and apparently lacks mediator activity. Here we show that yRad52 can load human Rad51 (hRAD51) onto ssDNA complexed with yeast RPA in vitro. This is biochemically equivalent to mediator activity because it depends on the C-terminal Rad51-binding region of yRad52 and on functional Rad52 RPA interaction. It has been reported that the N-terminal two thirds of both yRad52 and hRAD52 is essential for binding to and annealing ssDNA. Although a second DNA binding region has been found in the C-terminal region of yRad52, its role in ssDNA annealing is not clear. In this paper, we also show that the C terminal region of yRad52, but not of hRAD52, is involved in ssDNA annealing. This suggests that the second DNA binding site is required for the efficient ssDNA annealing by yRad52. We propose an updated model of Rad52-mediated ssDNA annealing. PMID- 27362512 TI - Sleep Disturbance, Daytime Symptoms, and Functional Performance in Patients With Stable Heart Failure: A Mediation Analysis. AB - BACKGROUND: Sleep disturbance is common among patients with heart failure (HF) who also experience symptom burden and poor functional performance. OBJECTIVE: We evaluated the extent to which sleep-related, daytime symptoms (fatigue, excessive daytime sleepiness, and depressive symptoms) mediate the relationship between sleep disturbance and functional performance among patients with stable HF. METHODS: We recruited patients with stable HF for this secondary analysis of data from a cross-sectional, observational study. Participants completed unattended ambulatory polysomnography from which the Respiratory Disturbance Index was calculated, along with a Six-Minute Walk Test, questionnaires to elicit sleep disturbance (Pittsburgh Sleep Quality Index, Insomnia Symptoms from the Sleep Habits Questionnaire), daytime symptoms (Center for Epidemiologic Studies Depression Scale, Global Fatigue Index, Epworth Sleepiness Scale), and self reported functional performance (Medical Outcomes Study SF36 V2 Physical Function Scale). We used structural equation modeling with latent variables for the key analysis. Follow-up, exploratory regression analysis with bootstrapped samples was used to examine the extent to which individual daytime symptoms mediated effects of sleep disturbance on functional performance after controlling for clinical and demographic covariates. RESULTS: The sample included 173 New York Heart Association Class I-IV HF patients (n = 60/34.7% women; M = 60.7, SD = 16.07 years of age). Daytime symptoms mediated the relationship between sleep disturbance and functional performance. Fatigue and depression mediated the relationship between insomnia symptoms and self-reported functional performance, whereas fatigue and sleepiness mediated the relationship between sleep quality and functional performance. Sleepiness mediated the relationship between the respiratory index and self-reported functional performance only in people who did not report insomnia. CONCLUSIONS: Daytime symptoms explain the relationships between sleep disturbance and functional performance in stable HF. PMID- 27362513 TI - Symptom Trajectories After an Emergency Department Visit for Potential Acute Coronary Syndrome. AB - BACKGROUND: Many patients evaluated for acute coronary syndrome (ACS) in emergency departments (EDs) continue to experience troubling symptoms after discharge-regardless of their ultimate medical diagnosis. However, comprehensive understanding of common post-ED symptom trajectories is lacking. OBJECTIVES: The aim of this study was to identify common trajectories of symptom severity in the 6 months after an ED visit for potential ACS. METHODS: This was a secondary analysis of data from a larger observational, prospective study conducted in five U.S. EDs. Patients (N = 1005) who had electrocardiogram and biomarker testing ordered, and were identified by the triage nurse as potentially having ACS, were enrolled. Symptom severity was assessed in the hospital after initial stabilization and by telephone at 30 days and 6 months using the validated 13 item ACS Symptom Checklist. Growth mixture modeling was used for the secondary analysis. The eight most commonly reported symptoms (chest discomfort, chest pain, chest pressure, light-headedness, shortness of breath, shoulder pain, unusual fatigue, and upper back pain) were modeled across the three study time points. Models with increasing numbers of classes were compared, and final model selection was based on a combination of interpretability, theoretical justification, and statistical fit indices. RESULTS: The sample was 62.6% male with a mean age of 60.2 years (SD = 14.17 years), and 57.1% ruled out for ACS. Between two and four distinct trajectory classes were identified for each symptom. The seven different types of trajectories identified across the eight symptoms were labeled "tapering off," "mild/persistent," "moderate/persistent," "moderate/worsening," "moderate/improving," "late onset, "and "severe/improving." Trajectories differed on age, gender, and diagnosis. DISCUSSION: Research on the individual nature of symptom trajectories can contribute to patient-centered, rather than disease-centered, care. Further research is needed to verify the existence of multiple symptoms trajectories in diverse populations and to assess the antecedents and consequences of individual symptom trajectories. PMID- 27362515 TI - Pain Intensity in Hospitalized Adults: A Multilevel Analysis of Barriers and Facilitators of Pain Management. AB - BACKGROUND: Despite an enhanced interest and evolution in pain management, prevalence remains high. Interventions to optimize pain-related care can only be effective if barriers are identified and accounted for. AIM: To assess pain intensity and examine its association with patient- (including health literacy defined in this study as "requiring help to read health information"), nurse-, and system-related (including social capital defined as "the importance of network and norms at work") barriers/facilitators to pain management. METHODS: A two-center, cross-sectional study was performed between October 2012 and April 2013. The study included patients and nurses of 39 noncritical wards of two hospitals in Belgium. Patients who were 18 years of age or older and without impaired cognition or consciousness were eligible to take part. All nurses working in the included ward were invited to participate. Pain intensity and patient-related barriers were collected by a structured and standardized questionnaire, completed in dialogue with the patient. Nurses completed the questionnaire on the nurse- and system-related barriers and the social capital scale. Multilevel analysis was used to analyze the data because of the hierarchical structure of the data. RESULTS: The average pain of all patients across all wards on a 0-10 scale was 2.2 (SD = 3.6). The multilevel analysis indicates that pain intensity can be explained by variables at patient and ward levels. A significant independent association was found between higher pain intensity and younger age, receiving pain medication, the conviction of patients that pain medication does not improve pain, inadequate health literacy in patients, nurses without advanced education, and nurse's concerns about side effects. Social capital did not emerge as predictor of pain intensity. DISCUSSION: Patient and nurse level factors should be taken into account in hospitals when setting up strategies to improve pain management. PMID- 27362516 TI - Adolescent Experience of Menstruation in Rural Kenya. AB - BACKGROUND: Although menstruation is a universal experience, girls in resource poor areas face unique challenges related to menstruation management. In Kenya, girls miss nearly 3.5 million learning days per month because of limited access to sanitary products and lack of adequate sanitation. Global priorities to address gender inequality-especially related to education-often do not consider the impact of poverty on gendered experiences, such as menstruation. OBJECTIVE: The aim of the study was to describe the experiences of menstruation from the perspective of adolescent girls living in rural Kenya. METHODS: Data for this qualitative study were collected through 29 individual interviews with adolescent girls and separate field observations. Descriptive content analysis was used to identify themes reflective of the data from the individual interviews and field notes. RESULTS: Four themes were developed to summarize the data: (a) receiving information about menstruation, (b) experiences of menstruation, (c) menstrual hygiene practices, and (d) social norms and the meaning of menstruation. CONCLUSIONS: Findings from this study describe the impact of menstruation on the lives of adolescent girls in rural Kenya. Menstrual hygiene management and its associated challenges may impact girls' academic continuity. Experiences of menstruation also reinforce gender inequality and further marginalize girls in low-income, rural areas of Kenya. Consideration of menstruation is critical to promote health and academic continuity for girls in rural Kenya. PMID- 27362517 TI - Repetition in the Health History Segment of Spanish Language Clinical Consultations: A Conversation Analysis. AB - BACKGROUND: Patient history-taking sequences may be repeated across medical speech events with different healthcare providers and subsequently co-constructed differently, which can lead to disparate patient history information with implications for patient care outcomes. Encounters that include language discordance between patients with limited English language proficiency and healthcare workers can also impact patient outcomes. OBJECTIVES: We examined the repetition of patient history-taking sequences in consultations in which healthcare providers used Spanish as a first and second language with monolingual Spanish-speaking patients. The aim was to understand how repetition affects patient care processes and outcomes. METHODS: Conversation analysis was used. The target population was bilingual healthcare providers and monolingual Spanish speaking patients. The accessible population was composed of healthcare providers and patients from an urban, low-income, community health clinic in Southern California. In three exemplar cases from among 50 that were studied, instances of repetition in the history-taking segment of clinical consultations were located. We identified which aspects of patient reports were repeated across intake nurse patient consultations and nurse practitioner-patient consultations, as well as how patient reports were differently co-constructed across these events. RESULTS: Information elicited during the intake nurse-patient history event may be elicited again when a nurse practitioner repeats the elicitation of particular aspects of the patient's complaints and health history. Repetition of patient history information was co-constructed differently by different healthcare providers, sometimes led to seamless teamwork, and sometimes led to time wasting. Healthcare provider second language use of Spanish did not substantially impact how patient history information was co-constructed. DISCUSSION: This analysis sheds light on the effects of repetition across medical events and assessed the effects of repetition on communication among members of a healthcare team and patient care outcomes. It also informs how medical provider second language use may affect how information is conveyed. Our study has implications for understandings of medical consultations that involve nurse triage prior to consultation time in multilingual settings. PMID- 27362514 TI - Psychometric Evaluation of the Patient-Reported Outcomes Measurement Information System Fatigue-Short Form Across Diverse Populations. AB - BACKGROUND: The need for reliable, valid tools to measure patient-reported outcomes (PROs) is critical both for research and for evaluating treatment effects in practice. The Patient-Reported Outcomes Measurement Information System Fatigue-Short Form v1.0-Fatigue 7a (PROMIS F-SF) has had limited psychometric evaluation in various populations. OBJECTIVES: The aim of the study is to examine psychometric properties of PROMIS F-SF item responses across various populations. METHODS: Data from five studies with common data elements were used in this secondary analysis. Samples from patients with fibromyalgia, sickle cell disease, cardiometabolic risk, pregnancy, and healthy controls were used. Reliability was estimated using Cronbach's alpha. Dimensionality was evaluated with confirmatory factor analysis. Concurrent validity was evaluated by examining Pearson's correlations between scores from the PROMIS F-SF, the Multidimensional Fatigue Symptom Inventory-Short Form, and the Brief Fatigue Inventory. Discriminant validity was evaluated by examining Pearson's correlations between scores on the PROMIS F-SF and measures of stress and depressive symptoms. Known groups validity was assessed by comparing PROMIS F-SF scores in the clinical samples to healthy controls. RESULTS: Reliability of PROMIS F-SF scores was adequate across samples, ranging from .72 in the pregnancy sample to .88 in healthy controls. Unidimensionality was supported in each sample. Concurrent validity was strong; across the groups, correlations with scores on the Multidimensional Fatigue Symptom Inventory-Short Form and Brief Fatigue Inventory ranged from .60 to .85. Correlations of the PROMIS F-SF with measures of stress and depressive mood were moderate to strong, ranging from .37 to .64. PROMIS F-SF scores were significantly higher in clinical samples compared to healthy controls. DISCUSSION: Reliability and validity of the PROMIS F-SF were acceptable. The PROMIS F-SF is a suitable measure of fatigue across the four diverse clinical populations included in the analysis. PMID- 27362518 TI - Pharmacogenetics of Anesthesia: An Integrative Review. AB - BACKGROUND: Monitoring a patient's response to drug therapy and early identification of an adverse reaction are important responsibilities of nurses. Despite the relative safety of anesthesia practice, 1 in 20 perioperative medication administrations includes a medication error and/or adverse drug reaction. Although several factors contribute to an individual's response to medications, genetic predisposition accounts for over 50% of that response. OBJECTIVE: The purpose of this review is to explore the evidence of genetic variability associated with response to volatile and intravenous anesthetics. METHODS: A comprehensive search of published literature in PubMed, CINAHL, and Cochrane databases from 1960 to May 30, 2015, was performed. Iterative reading of the primary articles was performed to ensure congruence between the extracted data and the primary article and reduce the data to draw conclusions. RESULTS: The analysis revealed that most anesthetics are metabolized by enzymes in the CYP2 and UGT1 family. CYP2B6 catalyzes propofol and ketamine metabolism. CYP2B6*6 allele is associated with decreased propofol and ketamine metabolism and increased adverse effects. Genetic variants in the UGT1A9 enzyme are associated with the need for higher induction dose and increased clearance of propofol. DISCUSSION: Despite the significant gaps in the literature, current evidence suggests that close monitoring is required when administering anesthetics to individuals with the CYP2B6*6 allele. Future research to address identified gaps in this review may have the potential to identify underlying genetic contribution to anesthetic response and prevent significant adverse events during anesthesia delivery and perioperative nursing care. PMID- 27362520 TI - Human immune-cell response towards diverse xenogeneic and allogeneic decellularized biomaterials. AB - BACKGROUND: Immunological knowledge on processed biological implants and mesh prostheses is still mainly based on animal models, lacking information on the species-specific human immune response. We hypothesized that in contrast to human tissue even decellularized xenogenic specimens would lead to significant and tissue source dependent human immune reactions. METHODS: Specimens from processed allogenic and xenogenic pulmonary arteries, pericardium or dermis, were co cultured with human peripheral blood mononuclear cells (PBMNC). Proliferative responses were measured in tritiated thymidine incorporation assays (n = 10). Stimulation indices (SI), calculated as counts-per-minute of co-cultured PBMNC divided by the cpm of basic cell proliferation, were compared. RESULTS: Compared to native porcine pulmonary artery tissue decellularization significantly reduced human PBMNC proliferation (mean SI: 48.7 vs. 18.0, p < 0.01), which was still higher compared to the human equivalent (SI: 0.7 vs. 1.7). Also the processed human dermal implant did not elicit immune response (SI: 1.5), whereas the decellularized and cross-linked porcine dermis lead to a significant human cell proliferation (SI: 8.4, p < 0.01). Interestingly, both the processed human (SI: 15.2) and bovine pericardial patches (SI: 15.1) led to higher immune cell proliferation. CONCLUSION: Even decellularized or cross-linked xenogenic cardiovascular and reconstructive biomaterials elicit increased human immune responses not seen in the majority of allogenic specimens tested. PMID- 27362519 TI - The Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure Study (InterGEN): Design and Methods for Recruitment and Psychological Measures. AB - BACKGROUND: Although studies show that genomics and environmental stressors affect blood pressure, few studies have examined their combined effects, especially in African Americans. OBJECTIVE: We present the recruitment methods and psychological measures of the Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure (InterGEN) study, which seeks to investigate the individual and combined effects of genetic (G) and environmental (E) (psychological) stressors on blood pressure in African American mother-child dyads. Genetic methods are presented elsewhere, but here we present the recruitment methods, psychological measures, and analysis plan for these environmental stressors. METHODS: This longitudinal study will enroll 250 mother child dyads (N = 500). Study participation is restricted to women who (a) are <=21 years of age, (b) self-identify as African American or Black, (c) speak English, (d) do not have an identified mental illness or cognitive impairment, and (e) have a biological child between 3 and 5 years old. The primary environmental stressors assessed are parenting stress, perceived racism and discrimination, and maternal mental health. Covariates include age, cigarette smoking (for mothers), and gender (for children). The study outcome variables are systolic and diastolic blood pressure. ANALYSIS: The main analytic outcome is genetic-by-environment interaction analyses (G * E); however, main effects (G) and (E) will be individually assessed first. Genetic (G) and interaction analyses (G * E) are described in a companion paper and will include laboratory procedures. Statistical modeling of environmental stressors on blood pressure will be done using descriptive statistics and generalized estimating equation models. IMPLICATIONS: The methodology presented here includes the study rationale, community engagement and recruitment protocol, psychological variable measurement, and analysis plan for assessing the association of environmental stressors and blood pressure. This study may provide the foundation for other studies and development of interventions to reduce the risk for hypertension and to propose targeted health promotion programs for this high-risk population. PMID- 27362521 TI - The Effect of Age and Type of Noise on Speech Perception under Conditions of Changing Context and Noise Levels. AB - OBJECTIVE: Everyday life includes fluctuating noise levels, resulting in continuously changing speech intelligibility. The study aims were: (1) to quantify the amount of decrease in age-related speech perception, as a result of increasing noise level, and (2) to test the effect of age on context usage at the word level (smaller amount of contextual cues). PATIENTS AND METHODS: A total of 24 young adults (age 20-30 years) and 20 older adults (age 60-75 years) were tested. Meaningful and nonsense one-syllable consonant-vowel-consonant words were presented with the background noise types of speech noise (SpN), babble noise (BN), and white noise (WN), with a signal-to-noise ratio (SNR) of 0 and -5 dB. RESULTS: Older adults had lower accuracy in SNR = 0, with WN being the most difficult condition for all participants. Measuring the change in speech perception when SNR decreased showed a reduction of 18.6-61.5% in intelligibility, with age effect only for BN. Both young and older adults used less phonemic context with WN, as compared to other conditions. CONCLUSION: Older adults are more affected by an increasing noise level of fluctuating informational noise as compared to steady-state noise. They also use less contextual cues when perceiving monosyllabic words. Further studies should take into consideration that when presenting the stimulus differently (change in noise level, less contextual cues), other perceptual and cognitive processes are involved. PMID- 27362523 TI - Disentangling effects of socioeconomic status on obesity: A cross-sectional study of the Spanish adult population. AB - This paper complements previous estimations regarding socioeconomic inequalities in obesity for Spanish adults, and provides new evidence about the mechanisms through which socioeconomic status (SES) affects obesity. Microdata from the Spanish National Health Survey (SNHS) 2011-2012 are analysed. Corrected concentration indices (CCI) are calculated to measure inequality. Path analysis is employed to disentangle direct and indirect effects of SES on obesity, where dietary patterns, physical activity and sleep habits act as mediator variables. Multivariate logistic models are used to select those exogenous variables to be included in the path diagram. Men and women are analysed separately. Our results show significant pro-rich inequality in the distribution of obesity (the poorer the more obese), particularly for women (CCI=-0.070 for men, CCI=-0.079 for women). The indirect effects of SES on obesity (those transmitted via mediator variables) are quite modest (3.3% for males, 2.4% for females) due to three reasons. Firstly, dietary habits do not show a significant mediating effect. Secondly, the mediating effect of physical activity in leisure time, although significant (14% for males, 11.1% for females), is offset by that related to main activity. Finally, sleep habits contribution to total effect of SES on obesity is statistically significant but small (roughly 1%). Our results indicate that promoting physical activity in leisure time for those with a low SES, particularly for men, would contribute to prevent obesity and to reduce health inequalities. Promotion of adequate sleep habits for women with a low SES might have a similar effect. However, interventions aimed to reduce sedentarism related to main activity, although useful to prevent obesity, would amplify the obesity socioeconomic gradient. Since effects of SES are different for men and women, socioeconomic health inequalities should be addressed also from a gender perspective. PMID- 27362522 TI - Host-Imposed Copper Poisoning Impacts Fungal Micronutrient Acquisition during Systemic Candida albicans Infections. AB - Nutritional immunity is a process whereby an infected host manipulates essential micronutrients to defend against an invading pathogen. We reveal a dynamic aspect of nutritional immunity during infection that involves copper assimilation. Using a combination of laser ablation inductively coupled mass spectrometry (LA-ICP MS) and metal mapping, immunohistochemistry, and gene expression profiling from infected tissues, we show that readjustments in hepatic, splenic and renal copper homeostasis accompany disseminated Candida albicans infections in the mouse model. Localized host-imposed copper poisoning manifests itself as a transient increase in copper early in the kidney infection. Changes in renal copper are detected by the fungus, as revealed by gene expression profiling and fungal virulence studies. The fungus responds by differentially regulating the Crp1 copper efflux pump (higher expression during early infection and down-regulation late in infection) and the Ctr1 copper importer (lower expression during early infection, and subsequent up-regulation late in infection) to maintain copper homeostasis during disease progression. Both Crp1 and Ctr1 are required for full fungal virulence. Importantly, copper homeostasis influences other virulence traits-metabolic flexibility and oxidative stress resistance. Our study highlights the importance of copper homeostasis for host defence and fungal virulence during systemic disease. PMID- 27362524 TI - Mitochondrial Sirtuin 3 and Renal Diseases. AB - Mitochondria are dynamic organelles whose functions are tightly regulated at multiple levels to maintain proper cellular homeostasis. Mitochondrial Sirtuin 3 (SIRT3), which belongs to an evolutionary conserved family of NAD+-dependent deacetylases, is a key regulator of the mitochondrial respiratory chain, ATP production, and fatty acid beta-oxidation, and it exerts an antioxidant activity. Changes in SIRT3 expression are critical in the pathophysiology of several diseases, such as metabolic syndrome, diabetes, cancer, and aging. In experimental acute kidney injury (AKI), impairment of renal function and development of tubular injury are associated with SIRT3 reduction and mitochondrial dysfunction in proximal tubuli. SIRT3-deficient mice are more susceptible to AKI and die. Pharmacological manipulations able to increase SIRT3 preserve mitochondrial integrity, markedly limit renal injury, and accelerate functional recovery. This review highlights all the selective rescue mechanisms that point to the key role of SIRT3 as a new therapeutic target for curing renal diseases. PMID- 27362525 TI - Sperm mitochondrial DNA deletion in Iranian infertiles with asthenozoospermia. AB - Asthenozoospermia is an important cause of male infertility. The mutations in sperm mitochondrial DNA (mtDNA) result in either functionless or malfunctioning some proteins, subsequently affecting sperm motility leading to asthenozoospermia. The purpose of this study was to investigate sperm mtDNA 4,977 bp deletion in infertile men with low sperm motility/immotile spermatozoa compared to healthy subjects with high sperm motility. Semen samples of 256 asthenozoospermic infertiles and 200 controls from northern Iran were collected. After extraction of spermatozoa total DNA, Gap-polymerase chain reaction (Gap PCR) was performed. The deletion was observed in 85.93% of patients with asthenozoospermia compared with 14% in controls [OR = 37.5397, 95% confidence interval = 12.937-108.9276, p < .0001]. It is concluded that there is a strong association between sperm mtDNA 4,977-bp deletion and asthenozoospermia-induced infertility in the population examined. Large-scale mtDNA deletions in spermatozoa may induce bioenergetic disorders. Nevertheless, to validate our results broader research may be needed. PMID- 27362526 TI - Adherence to Technology-Based Exercise Programs in Older Adults: A Systematic Review. AB - BACKGROUND AND PURPOSE: Exercise participation and adherence in older people is often low. The integration of technology-based exercise programs may have a positive effect on adherence as they can overcome perceived barriers to exercise. Previous systematic reviews have shown preliminary evidence that technology-based exercise programs can improve physical functioning. However, there is currently no in-depth description and discussion of the potential this technology offers to improve exercise adherence in older people. This review examines the literature regarding older adults' acceptability and adherence to technology-based exercise interventions. METHODS: A comprehensive systematic database search for randomized controlled trials, clinical controlled trials, and parallel group trials was performed, including MEDLINE, PsycINFO, EMBASE, CINAHL, EMB Reviews, and Cochrane Library, completed in May 2015. Trials reporting adherence to technology-based exercise programs aimed at improving physical function were included. Adherence was defined as the percentage of exercise sessions attended out of the total number of sessions prescribed. RESULTS: Twenty-two studies were included. The mean cohort age range was 67 to 86 years. Studies were conducted in research facilities, aged care facilities, and people's homes. Ten studies compared outcomes between technology-based and traditional exercise programs. Adherence to both types of interventions was high (median 91.25% and 83.58%, respectively). Adherence was higher for technology-based interventions than traditional interventions independent of study site, level of supervision, and delivery mode. The majority of the studies used commercially available gaming technologies, and both types of exercise interventions were mostly supervised. A lack of detailed reporting of adherence and the pilot nature of most studies did not allow computation of a comprehensive adherence rate. DISCUSSION: This systematic review provides evidence that technology offers a well-accepted method to provide older adults with engaging exercise opportunities, and adherence rates remain high in both supervised and unsupervised settings at least throughout the first 12 weeks of intervention. The higher adherence rates to technology-based interventions can be largely explained by the high reported levels of enjoyment when using these programs. However, the small sample sizes, short follow-up periods, inclusion of mostly healthy older people, and problems related to the methods used to report exercise adherence limit the generalizability of our findings. CONCLUSION: This systematic review indicates that technology-based exercise interventions have good adherence and may provide a sustainable means of promoting physical activity and preventing falls in older people. More research is required to investigate the feasibility, acceptability, and effectiveness of technology-based exercise programs undertaken by older people at home over extended trial periods. PMID- 27362527 TI - A feature refinement approach for statistical interior CT reconstruction. AB - Interior tomography is clinically desired to reduce the radiation dose rendered to patients. In this work, a new statistical interior tomography approach for computed tomography is proposed. The developed design focuses on taking into account the statistical nature of local projection data and recovering fine structures which are lost in the conventional total-variation (TV)-minimization reconstruction. The proposed method falls within the compressed sensing framework of TV minimization, which only assumes that the interior ROI is piecewise constant or polynomial and does not need any additional prior knowledge. To integrate the statistical distribution property of projection data, the objective function is built under the criteria of penalized weighed least-square (PWLS-TV). In the implementation of the proposed method, the interior projection extrapolation based FBP reconstruction is first used as the initial guess to mitigate truncation artifacts and also provide an extended field-of-view. Moreover, an interior feature refinement step, as an important processing operation is performed after each iteration of PWLS-TV to recover the desired structure information which is lost during the TV minimization. Here, a feature descriptor is specifically designed and employed to distinguish structure from noise and noise-like artifacts. A modified steepest descent algorithm is adopted to minimize the associated objective function. The proposed method is applied to both digital phantom and in vivo Micro-CT datasets, and compared to FBP, ART-TV and PWLS-TV. The reconstruction results demonstrate that the proposed method performs better than other conventional methods in suppressing noise, reducing truncated and streak artifacts, and preserving features. The proposed approach demonstrates its potential usefulness for feature preservation of interior tomography under truncated projection measurements. PMID- 27362528 TI - Alkaline bioleaching of municipal solid waste incineration fly ash by autochthonous extremophiles. AB - The increasing demand for energy and the generation of solid waste have caused an alarming rise in fly ash production globally. Since heavy metals continue to be in demand for the production of materials, resource recovery from the recycling of these wastes has the potential to delay the depletion of natural ores. The use of microorganisms for the leaching of metals, in a process called bioleaching, is an eco-friendly and economical way to treat the metal-laden wastes. Bioleaching of fly ash is challenging due largely to the alkaline nature and toxic levels of heavy metals which are detrimental to microbial growth and bioleaching activity. The present work reports the isolation of indigenous bacteria from a local landfill site and their bioleaching performance [corrected]. 38 autochthonous strains of bacteria were isolated from eight samples collected and plated on five different media. 18 of the isolates showed bioleaching potential, with significant alkaline pH or fly ash tolerance. Genetic characterization of the strains revealed a dominance of Firmicutes, with Alkalibacterium sp. TRTYP6 showing highest fly ash tolerance of up to 20% w/v fly ash, and growth over a pH range 8-12.5. The organism selectively recovered about 52% Cu from the waste. To the best of our knowledge, this is the first time a study on bioleaching with extreme alkaliphiles is reported. PMID- 27362529 TI - Insights into asphaltene aggregation in the Na-montmorillonite interlayer. AB - This study aimed to provide insights into the diffusion and aggregation of asphaltenes in the Na-montmorillonite (MMT) interlayer with different water saturation, salinity, interlayer space and humic substances. The molecular configuration, density profile, diffusion coefficient and aggregation intensity were determined by molecular dynamic simulation, while the 3D topography and particle size of the aggregates were characterized by atomic force microscopy. Results indicated that the diffusivity of asphaltenes was up to 5-fold higher in the MMT interlayer filled with fresh water than with saline water (salinity: 350/00). However, salinity had little impact on the asphaltene aggregation. This study also showed a marked decrease in the mobility of asphaltenes with decrease in the pore water content and the interlayer space of MMT. This was more pronounced in the organo-MMT where the humic substances were present. The co aggregation process resulted in the sequestration of asphaltenes in the hollow cone-shaped cavity of humic substances in the MMT interlayer, which decreased the asphaltene diffusion by up to one-order of magnitude and increased the asphaltene aggregation by about 33%. These findings have important ramifications for evaluating the fate and transport of heavy fractions of the residual oil in the contaminated soils. PMID- 27362530 TI - Modeling corrosion inhibition efficacy of small organic molecules as non-toxic chromate alternatives using comparative molecular surface analysis (CoMSA). AB - Traditionally many structural alloys are protected by primer coatings loaded with corrosion inhibiting additives. Strontium Chromate (or other chromates) have been shown to be extremely effectively inhibitors, and find extensive use in protective primer formulations. Unfortunately, hexavalent chromium which imbues these coatings with their corrosion inhibiting properties is also highly toxic, and their use is being increasingly restricted by legislation. In this work we explore a novel tridimensional Quantitative-Structure Property Relationship (3D QSPR) approach, comparative molecular surface analysis (CoMSA), which was developed to recognize "high-performing" corrosion inhibitor candidates from the distributions of electronegativity, polarizability and van der Waals volume on the molecular surfaces of 28 small organic molecules. Multivariate statistical analysis identified five prototypes molecules, which are capable of explaining 71% of the variance within the inhibitor data set; whilst a further five molecules were also identified as archetypes, describing 75% of data variance. All active corrosion inhibitors, at a 80% threshold, were successfully recognized by the CoMSA model with adequate specificity and precision higher than 70% and 60%, respectively. The model was also capable of identifying structural patterns, that revealed reasonable starting points for where structural changes may augment corrosion inhibition efficacy. The presented methodology can be applied to other functional molecules and extended to cover structure-activity studies in a diverse range of areas such as drug design and novel material discovery. PMID- 27362531 TI - Effect of Spectral Domain Optical Coherence Tomography Image Quality on Macular Thickness Measurements and Error Rate. AB - PURPOSE: To evaluate the effect of Topcon spectral domain optical coherence tomography (OCT) image quality on macular thickness measurements and the error rate in healthy subjects and patients with clinically significant diabetic macular edema (CSME). METHODS: In this prospective, comparative case series, macular thickness measurements, and the rate of decentration and segmentation errors were evaluated before and after reducing the image quality factor (QF). The measurements were evaluated again after correcting the decentration and segmentation errors. To reduce the image QF below 45, tetracycline eye ointment was applied on the corneal surface. RESULTS: Forty eyes of 40 subjects including 18 healthy eyes and 22 eyes with CSME were included. In both groups, the difference in central subfield thickness measurements before and after reducing the image QF was not statistically significant both before and after error correction (all P>0.05). The rate of decentration error was statistically similar before and after reducing image QF in normal and CSME eyes (P=0.50, P=0.69, respectively). However, the rate of segmentation error was statistically significantly higher after reducing image QF both in normal and CSME eyes (P=0.008 and P=0.004, respectively). In both groups, eyes with a segmentation error had higher image QF reduction (both P=0.01). CONCLUSION: Reducing image quality results in a higher rate of the segmentation error in normal eyes and in eyes with CSME. PMID- 27362532 TI - The Distress Thermometer for screening for severe fatigue in newly diagnosed breast and colorectal cancer patients. AB - OBJECTIVE: Internationally, the Distress Thermometer and associated Problem List are increasingly used in oncology as screening tools for psychological distress. Cancer-related fatigue is common but often overlooked in clinical practice. We examined if severe fatigue in cancer patients can be identified with the fatigue item of the Problem List. METHODS: Newly diagnosed breast (N = 334) and colorectal (N = 179) cancer patients were screened for severe fatigue, which was defined as having a positive score on the fatigue item of the Problem List. The Fatigue Severity subscale of the Checklist Individual Strength was used as gold standard measure for severe fatigue. RESULTS: In total, 78% of breast cancer patients and 81% of colorectal cancer patients were correctly identified with the fatigue item. The sensitivity was 89% in breast cancer patients and 91% in colorectal cancer patients. The specificity was 75% in breast cancer patients and 77% in colorectal cancer patients. The positive predictive value was 53% in breast cancer patients and 64% in colorectal cancer patients, whereas the negative predictive value was 95% in both tumor types. CONCLUSIONS: The fatigue item of the Problem List performs satisfactorily as a quick screening tool for severe fatigue. However, a positive screen should be followed up with a more thorough assessment of fatigue, ie, a questionnaire with a validated cutoff point. Given time pressure of clinicians, this already implemented and brief screening tool may prevent severe fatigue from going undetected in clinical practice. PMID- 27362533 TI - Time Savings with Rituximab Subcutaneous Injection versus Rituximab Intravenous Infusion: A Time and Motion Study in Eight Countries. AB - BACKGROUND: Rituximab is a standard treatment for non-Hodgkin lymphoma. The SABRINA trial (NCT01200758) showed that a subcutaneous (SC) rituximab formulation did not compromise efficacy or safety compared with intravenous (IV) infusion. We aimed to quantify active healthcare professional (HCP) time and patient chair time for rituximab SC and IV, including potential time savings. METHODS: This non interventional time and motion study was run in eight countries and 30 day oncology units. Rituximab SC data were collected alongside the MabCute trial (NCT01461928); IV data were collected per routine real-world practice. Trained observers recorded active HCP time for pre-specified tasks (stopwatch) and chair time (time of day). A random intercept model was used to analyze active HCP time (by task and for all tasks combined) in the treatment room and drug preparation area, drug administration duration, chair time and patient treatment room time by country and/or across countries. Active HCP and chair time were extrapolated to a patient's first year of treatment (11 rituximab sessions). RESULTS: Mean active HCP time was 35.0 and 23.7 minutes for IV and SC process, respectively (-32%, p <0.0001). By country, relative reduction in time was 27-58%. Absolute reduction in extrapolated active HCP time (first year of treatment) was 1.1-5.2 hours. Mean chair time was 262.1 minutes for IV, including 180.9 minutes infusion duration, vs. 67.3 minutes for SC, including 8.3 minutes SC injection administration (-74%, p <0.0001). By country, relative reduction was 53-91%. Absolute reduction in extrapolated chair time for the first year of treatment was 3.1-5.5 eight-hour days. CONCLUSIONS: Compared with rituximab IV, rituximab SC was associated with reduced chair time and active HCP time. The latter could be invested in other activities, whereas the former may lead to more available appointments, reducing waiting lists and increasing the efficiency of day oncology units. TRIAL REGISTRATION: ClinicalTrials.gov NCT01200758. PMID- 27362534 TI - Genetic Variants of BMP2 and Their Association with the Risk of Non-Syndromic Tooth Agenesis. AB - Non-syndromic tooth agenesis (or non-syndromic congenitally missing tooth) is one of the most common congenital defects in humans affecting the craniofacial function and appearance. Single nucleotide polymorphisms (SNPs) have been associated with an individual's susceptibility to these anomalies. The aim of the present study was therefore to investigate the roles of the potentially functional SNPs of BMP2 in the occurrence of tooth agenesis. Overall, four potentially functional SNPs of BMP2 (rs15705, rs235768, rs235769 and rs3178250) were selected, and their associations with the susceptibility of tooth agenesis were evaluated in a case-control study of 335 non-syndromic tooth agenesis cases and 444 healthy controls. The SNPs rs15705 and rs3178250 were found to be associated with an individual's risk of tooth agenesis (P = 0.046 and P = 0.039, respectively). Both SNPs showed an increased risk of mandibular incisor agenesis (rs15705, AA/AC vs. CC = 1.58, 95% CI = [1.06-2.34], P = 0.024; rs3178250, TT/TC vs. CC = 1.60, 95% CI = [1.08-2.37], P = 0.020). Bioinformatics analysis indicated that these two SNPs located at the 3'-untranslated region (3'-UTR) of BMP2 might alter the binding ability of miR-1273d and miR-4639-5p, respectively, which was confirmed by luciferase activity assays in the 293A and COS7 cell lines (P < 0.001 in 293A and P < 0.01 in COS7 for miR-1273d; and P < 0.001 in both cells for miR-4639-5p). Furthermore, BMP2 mRNA expression decreased after transfecting either miR-1273d or miR-4639-5p into these two cell lines (P < 0.01 in 293A and P < 0.001 in COS7 for miR-1273d, and P < 0.01 in both cell lines for miR-4639-5p). Taken together, our findings indicate that rs15705 and rs317250 are associated with the susceptibility of non-syndromic tooth agenesis by possibly affecting miRNAs and mRNA interaction. PMID- 27362535 TI - DABO Boronate Promoted Conjugate Allylation of alpha,beta-Unsaturated Aldehydes Using Copper(II) Catalysis. AB - The first catalytic method for the selective 1,4-conjugate allylation of alpha,beta-unsaturated aldehydes is reported. The method employs an air-stable diethanolamine-complexed boronic acid (DABO boronate) as the allyl transfer reagent and promotes conjugate addition over 1,2-addition. A variety of aryl- and alkyl-substituted enals are tolerated, providing delta,epsilon-unsaturated aldehyde products in good yields and selectivities under mild conditions. PMID- 27362537 TI - Impact of Silicon Nanocrystal Oxidation on the Nonmetallic Growth of Carbon Nanotubes. AB - Carbon nanotube (CNT) growth has been demonstrated recently using a number of nonmetallic semiconducting and metal oxide nanoparticles, opening up pathways for direct CNT synthesis from a number of more desirable templates without the need for metallic catalysts. However, CNT growth mechanisms using these nonconventional catalysts has been shown to largely differ and reamins a challenging synthesis route. In this contribution we show CNT growth from partially oxidized silicon nanocrystals (Si NCs) that exhibit quantum confinement effects using a microwave plasma enhanced chemical vapor deposition (PECVD) method. On the basis of solvent and a postsynthesis frgamentation process, we show that oxidation of our Si NCs can be easily controlled. We determine experimentally and explain with theoretical simulations that the Si NCs morphology together with a necessary shell oxide of ~1 nm is vital to allow for the nonmetallic growth of CNTs. On the basis of chemical analysis post-CNT growth, we give insight into possible mechanisms for CNT nucleation and growth from our partially oxidized Si NCs. This contribution is of significant importance to the improvement of nonmetallic catalysts for CNT growth and the development of Si NC/CNT interfaces. PMID- 27362536 TI - Multispecies Outcomes of Sympatric Speciation after Admixture with the Source Population in Two Radiations of Nicaraguan Crater Lake Cichlids. AB - The formation of species in the absence of geographic barriers (i.e. sympatric speciation) remains one of the most controversial topics in evolutionary biology. While theoretical models have shown that this most extreme case of primary divergence-with-gene-flow is possible, only a handful of accepted empirical examples exist. And even for the most convincing examples uncertainties remain; complex histories of isolation and secondary contact can make species falsely appear to have originated by sympatric speciation. This alternative scenario is notoriously difficult to rule out. Midas cichlids inhabiting small and remote crater lakes in Nicaragua are traditionally considered to be one of the best examples of sympatric speciation and lend themselves to test the different evolutionary scenarios that could lead to apparent sympatric speciation since the system is relatively small and the source populations known. Here we reconstruct the evolutionary history of two small-scale radiations of Midas cichlids inhabiting crater lakes Apoyo and Xiloa through a comprehensive genomic data set. We find no signs of differential admixture of any of the sympatric species in the respective radiations. Together with coalescent simulations of different demographic models our results support a scenario of speciation that was initiated in sympatry and does not result from secondary contact of already partly diverged populations. Furthermore, several species seem to have diverged simultaneously, making Midas cichlids an empirical example of multispecies outcomes of sympatric speciation. Importantly, however, the demographic models strongly support an admixture event from the source population into both crater lakes shortly before the onset of the radiations within the lakes. This opens the possibility that the formation of reproductive barriers involved in sympatric speciation was facilitated by genetic variants that evolved in a period of isolation between the initial founding population and the secondary migrants that came from the same source population. Thus, the exact mechanisms by which these species arose might be different from what had been thought before. PMID- 27362538 TI - Recovery of metals from simulant spent lithium-ion battery as organophosphonate coordination polymers in aqueous media. AB - An innovative approach is proposed for the recycling of metals from a simulant lithium-ion battery (LIBs) waste aqueous solution. Phosphonate organic linkers are introduced as precipitating agents to selectively react with the metals to form coordination polymers from an aqueous solution containing Ni, Mn and Co in a hydrothermal process. The supernatant is analyzed by ICP-AES to quantify the efficiency and the selectivity of the precipitation and the materials are characterized by Scanning Electron Microscopy (SEM), Powder X-Ray Diffraction (PXRD), Thermogravimetric Analyses (TGA) and nitrogen gas sorption (BET). Conditions have been achieved to selectively precipitate Manganese or Manganese/Cobalt from this solution with a high efficiency. This work describes a novel method to obtain potentially valuable coordination polymers from a waste metal solution that can be generalized on any waste solution. PMID- 27362539 TI - Staging the progression to type 1 diabetes with prediagnostic markers. AB - PURPOSE OF REVIEW: There are an increasing number of markers that are used to predict the occurrence of type 1 diabetes (T1D), and to study the progression of pathologic changes prior to diagnosis. This review discusses some of those markers, particularly markers for which data are available that pertain to the progression to T1D. RECENT FINDINGS: A study of birth cohorts showed that young children who develop multiple autoantibodies are at a particularly high risk for developing T1D, and that there appears to be a typical sequence for autoantibody development. The measurement of autoantibodies by electrochemiluminescence can increase the prediction accuracy for T1D. A new marker of changes in glucose over 6 months (PS6 M) has potential utility as an endpoint in short-term prevention trials. Markers which combine C-peptide and glucose, such as the Diabetes Prevention Trial-Type 1 Risk Score and the Index60, can increase the accuracy of prediction, and can potentially be utilized as prediagnostic endpoints. beta-cell death measurements could have substantial utility in future T1D research. SUMMARY: Markers are highly useful for studying the prediction of and progression to T1D. Moreover, markers can possibly be utilized to diagnose T1D at an earlier stage of disease. PMID- 27362540 TI - Discovery of a Natural Microsporidian Pathogen with a Broad Tissue Tropism in Caenorhabditis elegans. AB - Microbial pathogens often establish infection within particular niches of their host for replication. Determining how infection occurs preferentially in specific host tissues is a key aspect of understanding host-microbe interactions. Here, we describe the discovery of a natural microsporidian parasite of the nematode Caenorhabditis elegans that displays a unique tissue tropism compared to previously described parasites of this host. We characterize the life cycle of this new species, Nematocida displodere, including pathogen entry, intracellular replication, and exit. N. displodere can invade multiple host tissues, including the epidermis, muscle, neurons, and intestine of C. elegans. Despite robust invasion of the intestine very little replication occurs there, with the majority of replication occurring in the muscle and epidermis. This feature distinguishes N. displodere from two closely related microsporidian pathogens, N. parisii and N. sp. 1, which exclusively invade and replicate in the intestine. Comparison of the N. displodere genome with N. parisii and N. sp. 1 reveals that N. displodere is the earliest diverging species of the Nematocida genus. Over 10% of the proteins encoded by the N. displodere genome belong to a single species-specific family of RING-domain containing proteins of unknown function that may be mediating interactions with the host. Altogether, this system provides a powerful whole-animal model to investigate factors responsible for pathogen growth in different tissue niches. PMID- 27362542 TI - Development of the Double Cyclic Peptide Ligand for Antibody Purification and Protein Detection. AB - Development of a peptide-based affinity matrix and detection reagent is important for biomedical research and the biopharmaceutical industry. In the present work, we designed and synthesized an immunoglobin G (IgG)-binding peptide ligand, Fc III-4C. Fc-III-4C is composed of 15 residues, and the 4 cysteine residues form 2 disulfide bonds to generate a double cyclic structure. The binding affinity of the Fc-III-4C peptide toward human IgG was determined to be 2.45 nM (Kd), which is higher than that of IgG with Protein A/G (Pro-A/G). Importantly, the Fc-III-4C peptide displayed high affinity to various IgGs from different species. Fc-III-4C immobilized agarose beads exhibited high stability and reusability when compared with that of the Pro-A/G-immobilized beads. The conjugate of Fc-III-4C with FITC was demonstrated to be suitable for immunofluorescence detection of proteins expressed in cells. These results demonstrate that the Fc-III-4C peptide is a useful affinity ligand for antibody purification and as a protein detection reagent. PMID- 27362541 TI - Alcohol Drinking Pattern: A Comparison between HIV-Infected Patients and Individuals from the General Population. AB - BACKGROUND: Alcohol consumption is highly prevalent in the general population and among HIV-infected population. This study aimed to compare the pattern of alcohol consumption and to describe characteristics associated with heavy alcohol consumption in individuals from the general population with patients infected with HIV. METHODS: Participants for this analysis came from a population-based cross-sectional study and from a consecutive sampling of patients infected with HIV. Participants aged 18 years or older were interviewed using similar questionnaires with questions pertaining to socio-demographic characteristics, alcohol consumption, smoking, physical activity, and HIV-related characteristics, among others. Blood pressure and anthropometric measures were measured using standardized procedures. RESULTS: Weekly alcohol consumption was more prevalent among individuals from the general population than HIV-infected patients: 57.0 vs. 31.1%, P<0.001. The prevalence of heavy episodic drinking was higher in the population sample as well: 46.1 vs. 17.0%, P<0.001. In the general population, heavy alcohol consumption was more prevalent in men. Cigarette smoking was independently associated with heavy alcohol consumption among HIV infected (Prevalence Ratio; PR = 5.9; 95%CI 2.6-13.9; P<0,001) and general population (PR = 2.6; 95%CI 1.9-3.0; P<0.001). Years at school were inversely associated with heavy alcohol consumption among HIV-infected patients and directly associated among participants from the general population, even after controlling for sex, age, skin color, and smoking. CONCLUSIONS: Heavy alcohol consumption is more prevalent in the general population than among HIV-infected patients. Individuals aware about their disease may reduce the amount of alcoholic beverages consumption comparatively to healthy individuals from the general population. PMID- 27362543 TI - Impaired glucose metabolism and bronchial hyperresponsiveness in obese prepubertal asthmatic children. AB - INTRODUCTION: The prevalence of asthma and obesity has risen in parallel over the last decades, but the exact mechanisms linking these two diseases still remain unclear. The aim of the present study was to investigate the associations between bronchial hyperresponsiveness (BHR), impaired glucose metabolism, obesity, and asthma in prepubertal children. METHODS: A total of 71 prepubertal children were included in the study and divided in four groups according to the presence of asthma and their Body Mass Index (BMI): Group 1-Healthy Controls (HC), Group 2 Non Obese Asthmatics (NOA), Group 3-Obese Non Asthmatics (ONA), Group 4-Obese Asthmatics (OA) Alphall children underwent spirometry and bronchial hyperresponsiveness testing by using the cumulative Provoking Dose of mannitol (PD15, primary study variable); homeostasis model assessment-estimated insulin resistance (HOMA-IR) index was calculated in order to evaluate insulin resistance. Obese children also underwent an oral glucose tolerance testing (OGTT). RESULTS: A statistically significant difference in bronchial hyperreactivity (mean +/- SD) was detected in the group of obese asthmatic children who had lower values of PD15 , (174.16 +/- 126.42) as compared to normal weight asthmatic children (453.93 +/- 110.27), (P < 0.001). Moreover, obese asthmatic children with confirmed insulin resistance (HOMA-IR >=2.5), had significantly lower PD15 values (89.05 +/- 42.75) as compared to those with HOMA IR <2.5 (259.27 +/- 125.75), (P = 0.006). Finally, obese asthmatic children with impaired OGTT had likewise significantly lower PD15 (81.02 +/- 42.16) measurements as compared to children with normal OGTT (267.3 +/- 112.62), (P = 0.001). CONCLUSION: Our findings suggest that obesity per se does not correlate to airway hyperreactivity unless it is accompanied by glucose intolerance and insulin resistance. Pediatr Pulmonol. 2017;52:160-166. (c) 2016 Wiley Periodicals, Inc. PMID- 27362544 TI - Microwave radiation (2.45 GHz)-induced oxidative stress: Whole-body exposure effect on histopathology of Wistar rats. AB - Man-made microwave and radiofrequency (RF) radiation technologies have been steadily increasing with the growing demand of electronic appliances such as microwave oven and cell phones. These appliances affect biological systems by increasing free radicals, thus leading to oxidative damage. The aim of this study was to explore the effect of 2.45 GHz microwave radiation on histology and the level of lipid peroxide (LPO) in Wistar rats. Sixty-day-old male Wistar rats with 180 +/- 10 g body weight were used for this study. Animals were divided into two groups: sham exposed (control) and microwave exposed. These animals were exposed for 2 h a day for 35 d to 2.45 GHz microwave radiation (power density, 0.2 mW/cm2). The whole-body specific absorption rate (SAR) was estimated to be 0.14 W/kg. After completion of the exposure period, rats were sacrificed, and brain, liver, kidney, testis and spleen were stored/preserved for determination of LPO and histological parameters. Significantly high level of LPO was observed in the liver (p < 0.001), brain (p < 0.004) and spleen (p < 0.006) in samples from rats exposed to microwave radiation. Also histological changes were observed in the brain, liver, testis, kidney and spleen after whole-body microwave exposure, compared to the control group. Based on the results obtained in this study, we conclude that exposure to microwave radiation 2 h a day for 35 d can potentially cause histopathology and oxidative changes in Wistar rats. These results indicate possible implications of such exposure on human health. PMID- 27362545 TI - Possession: Demoniacal and Other, Among Primitive Races, in Antiquity, the Middle Ages and Modern Times, by Traugott Konstantin Osterreich. PMID- 27362546 TI - Cytogenetic Analysis of the South American Fruit Fly Anastrepha fraterculus (Diptera:Tephritidae) Species Complex: Construction of Detailed Photographic Polytene Chromosome Maps of the Argentinian Af. sp.1 Member. AB - Genetic and cytogenetic studies constitute a significant basis for understanding the biology of insect pests and the design and the construction of genetic tools for biological control strategies. Anastrepha fraterculus is an important pest of the Tephritidae family. It is distributed from southern Texas through eastern Mexico, Central America and South America causing significant crop damage and economic losses. Currently it is considered as a species complex; until now seven members have been described based on multidisciplinary approaches. Here we report the cytogenetic analysis of an Argentinian population characterized as Af. sp.1 member of the Anastrepha fraterculus species complex. The mitotic karyotype and the first detailed photographic maps of the salivary gland polytene chromosomes are presented. The mitotic metaphase complement consists of six (6) pairs of chromosomes, including one pair of heteromorphic sex chromosomes, with the male being the heterogametic sex. The analysis of the salivary gland polytene complement shows a total number of five long chromosomes that correspond to the five autosomes of the mitotic karyotype and a heterochromatic network corresponding to the sex chromosomes. Comparison of the polytene chromosome maps between this species and Anastrepha ludens shows significant similarity. The polytene maps presented here are suitable for cytogenetic studies that could shed light on the species limits within this species complex and support the development of genetic tools for sterile insect technique (SIT) applications. PMID- 27362547 TI - Prognostic Significance of MAGE-A11 in Esophageal Squamous Cell Carcinoma and Identification of Related Genes Based on DNA Microarray. AB - BACKGROUND AND AIMS: This study aims to investigate the expression pattern of melanoma-associated antigen-A11 (MAGE-A11) in esophageal squamous cell carcinoma (ESCC) specimens and analyze its prognostic significance for ESCC patients. In addition, the purpose of our study was also to explore the biological function of MAGE-A11 in ESCC cells based on DNA microarray. METHODS: Immunohistochemistry was used to detect the expression of MAGE-A11 in ESCC specimens, and its prognostic significance was analyzed by statistical analysis. DNA microarray and quantitative RT-PCR were used to explore the different expression of MAGE-A11 downstream genes in ESCC cells. Cell invasion assay and MTT assay were used to detect the effect of MAGE-A11 cDNA on the invasion and proliferation of ESCC cells. RESULTS: Of the ESCC specimens, 59.3% showed positive MAGE-A11 expression. MAGE-A11 expression in ESCC specimens was positively associated with distant lymph node metastasis. Overall survival of ESCC patients with positive MAGE-A11 expression was shorter than in patients with negative MAGE-A11 expression. Multivariate Cox regression analysis showed MAGE-A11 expression is an independent poor prognostic factor for ESCC patients. Overexpression of MAGE-A11 changed a variety of gene expressions, which was associated with various cell functions such as protein ubiquitination, cell proliferation and apoptosis, tumor invasion and metastasis. Overexpression of MAGE-A11 directly increased the invasion and proliferation of ESCC cells. CONCLUSIONS: MAGE-A11 is an independent poor prognostic marker for ESCC patients. MAGE-A11 regulates various cell functions and directly increases the invasion and proliferation of ESCC cells. PMID- 27362548 TI - Tumor genotype and immune microenvironment in POLE-ultramutated and MSI hypermutated Endometrial Cancers: New candidates for checkpoint blockade immunotherapy? AB - Endometrial Cancer (EC) is still a challenge for gynecological oncologists because the treatment of the advanced disease remains an unmet need for patients. The Cancer Genome Atlas Research Network (TCGA) recently provided a comprehensive genomic and transcriptomic analysis of EC, offering a new classification of the disease, based on genetic features, which defines four subgroups of cancer rather than the two traditionally recognized. In the molecular classification two types of EC, the polymerase epsilon (POLE)-ultramutated and the microsatellite instability (MSI)-hypermutated, seem to present an enhanced immune microenvironment and a high mutation burden. The blockade of the immune checkpoints is an innovative approach that has largely demonstrated to be effective in solid malignancies, such as lung, renal and melanoma; it acts by reducing the cancer-induced immune-suppression through inhibition of the PD-1/PD L1 (Programmed Death and PD-Ligand) axis. All available evidence supporting an over-expression of the PD-1/PD-L1 pathway in EC has been reviewed. In particular in the POLE and MSI ECs an up-regulation of this pathway was found, aiming to suggest a rationale for testing the PD-1/PD-L1 immunotherapy in these cancer subgroups. PMID- 27362549 TI - Influence of preoperative sodium concentration on outcome of patients with hepatitis B virus cirrhosis after liver transplantation. AB - OBJECTIVES: Whether preoperative serum sodium concentration could influence post transplant patients' prognosis remains controversial. The aim of this study was to evaluate the influence of patients' pretransplant sodium concentration on the prognosis after liver transplantation in a cohort of patients with hepatitis B virus-related cirrhosis. PATIENTS AND METHODS: Data derived from the Chinese Liver Transplantation Registry system from 1 January 2000 to 31 December 2011 were extracted. The serum sodium concentrations and model for end-stage liver disease scores were recorded at listing before liver transplantation, and the relationship between the above parameters and patients' outcome was analyzed. RESULTS: A total of 2733 patients were included in this study. Compared with patients in the normal group (serum sodium between 135 and 150 mmol/l), patients in the severe hyponatremia group (<125 mmol/l) (P=0.022) and hypernatremia group (>150 mmol/l) (P=0.008) had a poorer prognosis. No significant differences were found among the moderate hyponatremia group (125-130 mmol/l) (P=0.113) and the mild hyponatremia group (130-135 mmol/l) (P=0.461). The 5-year cumulative survivals for the hyponatremia (<=135 mmol/l), normal (135-150 mmol/l), and hypernatremia (>=150 mmol/l) pretransplant group are 79.52, 82.23, and 69.30%, respectively. CONCLUSION: Our analysis showed that for patients with hepatitis B virus-related cirrhosis in mainland China, patients with abnormal serum sodium concentrations have poorer prognosis; both preoperative hyponatremia and hypernatremia were identified as negative risk factors for patients' outcome. PMID- 27362550 TI - Amyloidosis of the gastrointestinal tract and the liver: clinical context, diagnosis and management. AB - Amyloidosis is a group of disorders that can manifest in virtually any organ system in the body and is thought to be secondary to misfolding of extracellular proteins with subsequent deposition in tissues. The precursor protein that is produced in excess defines the specific amyloid type. This requires histopathological confirmation using Congo red dye with its characteristic demonstration of green birefringence under cross-polarized light. Gastrointestinal (GI) manifestations are common and the degree of organ involvement dictates the symptoms that a patient will experience. The small intestine usually has the most amyloid deposition within the GI tract. Patients generally have nonspecific findings such as abdominal pain, nausea, diarrhea, and dysphagia that can often delay the proper diagnosis. Liver involvement is seen in a majority of patients, although symptoms typically are not appreciated unless there is significant hepatic amyloid deposition. Pancreatic involvement is usually from local amyloid deposition that can lead to type 2 diabetes mellitus. In addition, patients may undergo either endoscopic or radiological evaluation; however, these findings are usually nonspecific. Management of GI amyloidosis primarily aims to treat the underlying amyloid type with supportive measures to alleviate specific GI symptoms. Liver transplant is found to have positive outcomes, especially in patients with specific variants of hereditary amyloidosis. PMID- 27362551 TI - Comparison of single-session transarterial chemoembolization combined with microwave ablation or radiofrequency ablation in the treatment of hepatocellular carcinoma: a randomized-controlled study. AB - BACKGROUND: Globally, hepatocellular carcinoma (HCC) is the third most frequent cause of cancer-related mortality. In recent years, transarterial chemoembolization, radiofrequency ablation, and microwave ablation (MWA) have been accepted as treatment modalities for patients with surgically unresectable HCC. AIM OF THIS WORK: This study aimed to compare combination treatment with radiofrequency or MWA, followed by transarterial chemoembolization, and performed in a single session. PATIENTS AND METHODS: This study was carried out on 50 patients with nonresectable single-lesion HCC, who were divided into three groups: group A included 20 patients treated by transcatheter hepatic arterial chemoembolization, group B included 20 patients treated by radiofrequency thermal ablation combined with transcatheter arterial chemoembolization, and group C included 10 patients treated by MWA combined with transcatheter arterial chemoembolization. The combined treatments were performed in a single session, with the ablation performed first. RESULTS: The total success rate in this study at 6 months following the procedure was 50% in group A, 70% in group B, and 80% in group C. Major complications were recorded in 22% of patients. The number of complications was the highest in group A. CONCLUSION: Combined ablation with chemoembolization is superior in the treatment of nonresectable single masses larger than 4 cm. Transcatheter arterial chemoembolization and ablation can be performed safely and successfully during a single session, which has not been found to decrease the response rates to treatment. Combined treatment with MWA is more effective in terms of tumor response, and results in the same complication rate as with radiofrequency, but less than chemoembolization alone. PMID- 27362552 TI - The Effect of the Type and Colour of Placebo Stimuli on Placebo Effects Induced by Observational Learning. AB - Research shows that placebo analgesia and nocebo hyperalgesia can be induced through observational learning. Our aim was to replicate and extend these results by studying the influence of the type and colour of stimuli used as placebos on the placebo effects induced by observational learning. Three experimental and two control groups were tested. All participants received pain stimuli of the same intensity preceded by colour lights (green and red) or geometric shapes (circles and squares). Before receiving pain stimuli, participants in the experimental groups, but not in the control groups, observed a model who rated pain stimuli that were preceded by either green lights (green placebo group), red lights (red placebo group), or circles (circle placebo group) as being less painful than those preceded by either red lights (green placebo group), green lights (red placebo group), or squares (circle placebo group). As a result participants in the experimental groups rated pain stimuli preceded by either green lights (green placebo group), red lights (red placebo group), or circles (circle placebo group) as being less painful than the participants in the control groups did, indicating that placebo effect was induced. No statistically significant differences were found in the magnitudes of the placebo effects between the three experimental groups (green placebo, red placebo, and circle placebo groups), indicating that neither the type nor the colour of placebo stimuli affected the placebo effects induced by observational learning. The placebo effects induced by observational learning were found to be unrelated to the individual differences in pain anxiety, fear of pain, and empathy. PMID- 27362553 TI - Tay-Sachs Carrier Screening by Enzyme and Molecular Analyses in the New York City Minority Population. AB - BACKGROUND AND AIMS: Carrier screening for Tay-Sachs disease is performed by sequence analysis of the HEXA gene and/or hexosaminidase A enzymatic activity testing. Enzymatic analysis (EA) has been suggested as the optimal carrier screening method, especially in non-Ashkenazi Jewish (non-AJ) individuals, but its utilization and efficacy have not been fully evaluated in the general population. This study assesses the reliability of EA in comparison with HEXA sequence analysis in non-AJ populations. METHODS: Five hundred eight Hispanic and African American patients (516 samples) had EA of their leukocytes performed and 12 of these patients who tested positive by EA ("carriers") had subsequent HEXA gene sequencing performed. RESULTS: Of the 508 patients, 25 (4.9%) were EA positive and 40 (7.9%) were inconclusive. Of the 12 patients who were sequenced, 11 did not carry a pathogenic variant and one carried a likely deleterious mutation (NM_000520.4(HEXA):c.1510C>T). CONCLUSIONS: High inconclusive rates and poor correlation between positive/inconclusive enzyme results and identification of pathogenic mutations suggest that ethnic-specific recalibration of reference ranges for EA may be necessary. Alternatively, HEXA gene sequencing could be performed. PMID- 27362554 TI - Cooperative Effects Between Arginine and Glutamic Acid in the Amino Acid Catalyzed Aldol Reaction. AB - Catalysis of the aldol reaction between cyclohexanone and 4-nitrobenzaldehyde by mixtures of L-Arg and of L-Glu in wet dimethyl sulfoxide (DMSO) takes place with higher enantioselectivity (up to a 7-fold enhancement in the anti-aldol for the 1:1 mixture) than that observed when either L-Glu or L-Arg alone are used as the catalysts. These results can be explained by the formation of a catalytically active hydrogen-bonded complex between both amino acids, and demonstrate the possibility of positive cooperative effects in catalysis by two different alpha amino acids. Chirality 28:599-605, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27362555 TI - Water-Free Proton Conduction in Discotic Pyridylpyrazolate-based Pt(II) and Pd(II) Metallomesogens. AB - In this work we report on water-free proton conductivity in liquid-crystal pyridylpyrazolate-based Pt(II) and Pd(II) complexes [M(pz(R(n,n)py))2] (pz(R(n,n)py) = 3-(3,5-dialkyloxyphenyl)-5-(pyridin-2-yl)pyrazolate, R(n,n) = C6H3(OCnH2n+1)2; n = 4, 12, 16, M = Pd; n = 12, M = Pt) with potential application as electrolyte materials in proton exchange membrane fuel cells. The columnar ordering of the complexes in the liquid-crystalline phase opens nanochannels, which are used for fast proton exchange as detected by impedance spectroscopy and NMR. The NMR spectra indicate that the proton conduction mechanism is associated with a novel C-H...N proton transfer, which persists above the clearing point of the material. The highest conductivity of ~0.5 MUS cm(-1) at 180 degrees C with an activation energy of 1.2 eV is found for the Pt(II) compound in the mesophase. The Pd(II) complexes with different chain length (n = 4, 12, and 16) show lower conductivity but smaller activation energies, in the range of 0.74-0.93 eV. PMID- 27362556 TI - On the Non-Stationary Relationship between the Siberian High and Arctic Oscillation. AB - An area-weighted k-means clustering method based on pattern correlations is proposed and used to explore the relationship between the Siberian High (SH) and Arctic Oscillation (AO) during the winter months (December-January-February) of 1948-2014. Five regimes are identified. Four of these five regimes (comprising 171 of 201 months) show a negative correlation between the SH and AO indices, while the last regime (30 months) shows a positive correlation. The location of the SH shifts southward into China under two of the four negative-correlation regimes (117 months), with pressure variations over the center of activity for the SH opposite to pressure variations over the climatological center of the SH (which is used to define the SH index). Adjusting the SH index to account for these spatial shifts suggests positive rather than negative correlations between major variations in the SH and AO under these regimes. Under one of the two remaining negative-correlation regimes, pressure anomalies are weak over the Arctic Ocean. In total, only one regime comprising 21 of 201 months strictly obeys the negative correlation between the SH and AO reported by previous studies. The climate regime characterized by an intensified SH is associated with a greater frequency of cold surges over northern and southeastern China, and the weakening of the East Asian winter monsoon during the 1980s was accompanied by a sharp reduction in the occurrence of this regime. PMID- 27362557 TI - Infection avoidance behavior: Viral exposure reduces the motivation to forage in female Drosophila melanogaster. AB - Infection avoidance behaviors are the first line of defense against pathogenic encounters. Behavioral plasticity in response to internal or external cues of infection can therefore generate potentially significant heterogeneity in infection. We tested whether Drosophila melanogaster exhibits infection avoidance behavior, and whether this behavior is modified by prior exposure to Drosophila C Virus (DCV) and by the risk of DCV encounter. We examined 2 measures of infection avoidance: (1) the motivation to seek out food sources in the presence of an infection risk and (2) the preference to land on a clean food source over a potentially infectious source. While we found no evidence for preference of clean food sources over potentially infectious ones, previously exposed female flies showed lower motivation to pick a food source when presented with a risk of encountering DCV. We discuss the relevance of behavioral plasticity during foraging for host fitness and pathogen spread. PMID- 27362558 TI - Endothelial cell dysfunction as a novel therapeutic target in atherosclerosis. AB - INTRODUCTION: Dysfunction of vessel endothelium is the first step in a complex and multi-faceted process that eventually leads to initiation of the plaque, formation of atherosclerotic lesions and their complications. The extremely fine regulated endothelium is the gatekeeper of vascular health, and has been the target of a substantial amount of research. AREAS COVERED: This review examines some of the most common associations between therapies of cardiovascular disease and the endothelium, and summarizes the direction of research that may set the stage for one or more interventions targeted to repair damaged and/or dysfunctional endothelium. Expert commentary: Routine treatment of cardiovascular disease has frequently been shown to have a positive effect on the vascular endothelium. The big question - whether the impact is due to a direct pharmacological effect or whether the function of the endothelium improves as a result of a general improvement in the underlying disease state, is still largely unanswered. PMID- 27362559 TI - Efficient and Reliable Production of Vectors for the Study of the Repair, Mutagenesis, and Phenotypic Consequences of Defined DNA Damage Lesions in Mammalian Cells. AB - Mammalian cells are constantly and unavoidably exposed to DNA damage from endogenous and exogenous sources, frequently to the detriment of genomic integrity and biological function. Cells acquire a large number of chemically diverse lesions per day, and each can have a different genetic fate and biological consequences. However, our knowledge of how and when specific lesions are repaired or how they may compromise the fidelity of DNA replication or transcription and lead to deleterious biological endpoints in mammalian cells is limited. Studying individual lesions requires technically challenging approaches for the targeted introduction of defined lesions into relevant DNA sequences of interest. Here, we present a systematic analysis of factors influencing yield and an improved, efficient and reliable protocol for the production of mammalian expression phagemid vectors containing defined DNA base modifications in any sequence position of either complementary DNA strand. We applied our improved protocol to study the transcriptional mutagenesis-mediated phenotypic consequences of the common oxidative lesion 5-hydroxyuracil, placed in the G12 mutational hotspot of the KRAS oncogene. 5-OHU induced sustained oncogenic signaling in Neil1-/-Neil2-/- mouse cells. The resulting advance in technology will have broad applicability for investigation of single lesion DNA repair, mutagenesis, and DNA damage responses in mammalian cells. PMID- 27362560 TI - Inducible RasGEF1B circular RNA is a positive regulator of ICAM-1 in the TLR4/LPS pathway. AB - Circular RNAs (circRNAs) constitute a large class of RNA species formed by the back-splicing of co-linear exons, often within protein-coding transcripts. Despite much progress in the field, it remains elusive whether the majority of circRNAs are merely aberrant splicing by-products with unknown functions, or their production is spatially and temporally regulated to carry out specific biological functions. To date, the majority of circRNAs have been cataloged in resting cells. Here, we identify an LPS-inducible circRNA: mcircRasGEF1B, which is predominantly localized in cytoplasm, shows cell-type specific expression, and has a human homolog with similar properties, hcircRasGEF1B. We show that knockdown of the expression of mcircRasGEF1B reduces LPS-induced ICAM-1 expression. Additionally, we demonstrate that mcircRasGEF1B regulates the stability of mature ICAM-1 mRNAs. These findings expand the inventory of functionally characterized circRNAs with a novel RNA species that may play a critical role in fine-tuning immune responses and protecting cells against microbial infection. PMID- 27362561 TI - Quantitative Phosphoproteomics Reveals Signaling Mechanisms Associated with Rapid Cold Hardening in a Chill-Tolerant Fly. AB - Rapid cold hardening (RCH) is a physiological adaptation in which brief chilling (minutes to hours) significantly enhances the cold tolerance of insects. RCH allows insects to cope with sudden cold snaps and diurnal variation in temperature, but the mechanistic basis of this rapid stress response is poorly understood. Here, we used phosphoproteomics to identify phosphorylation-mediated signaling events that are regulated by chilling that induces RCH. Phosphoproteomic changes were measured in both brain and fat bodies, two tissues that are essential for sensing cold and coordinating RCH at the organismal level. Tissues were chilled ex vivo, and changes in phosphoprotein abundance were measured using 2D electrophoresis coupled with Pro-Q diamond labeling of phosphoproteins followed by protein identification via LC-MS/MS. In both tissues, we observed an abundance of protein phosphorylation events in response to chilling. Some of the proteins regulated by RCH-inducing chilling include proteins involved in cytoskeletal reorganization, heat shock proteins, and proteins involved in the degradation of damaged cellular components via the proteasome and autophagosome. Our results suggest that phosphorylation-mediated signaling cascades are major drivers of RCH and enhance our mechanistic understanding of this complex phenotype. PMID- 27362562 TI - Independent Prognostic Value of Single and Multiple Non-Specific 12-Lead Electrocardiographic Findings for Long-Term Cardiovascular Outcomes: A Prospective Cohort Study. AB - AIMS: The long-term prognostic effect of non-specific 12-lead electrocardiogram findings is unknown. We aimed to evaluate the cumulative prognostic impact of axial, structural, and repolarization categorical abnormalities on cardiovascular death, independent from traditional risk scoring systems such as the Framingham risk score and the NIPPON DATA80 risk chart. METHODS AND RESULTS: A total of 16,816 healthy men and women from two prospective, longitudinal cohort studies were evaluated. 3,794 (22.6%) individuals died during a median follow-up of 15 years (range, 2.0-24 years). Hazard ratios for cardiovascular death, all-cause death, coronary death and stroke death were calculated for the cumulative and independent axial, structural, and repolarization categorical abnormalities adjusted for the Framingham risk score and the NIPPON DATA80 risk chart. Individuals with two or more abnormal categories had a higher risk of cardiovascular death after adjustment for Framingham risk score (men: HR 4.27, 95%CI 3.35-5.45; women: HR 4.83, 95%CI 3.76-6.22) and NIPPON DATA80 risk chart (men: HR 2.39, 95%CI 1.87-3.07; women: HR 2.04, 95%CI 1.58-2.64). CONCLUSION: Cumulative findings of axial, structural, and repolarization abnormalities are significant predictors of long-term cardiovascular death in asymptomatic, healthy individuals independent of traditional risk stratification systems. PMID- 27362564 TI - Erratum. PMID- 27362563 TI - Cultivar Mixture Cropping Increased Water Use Efficiency in Winter Wheat under Limited Irrigation Conditions. AB - The effects of cultivar mixture cropping on yield, biomass, and water use efficiency (WUE) in winter wheat (Triticum aestivum L.) were investigated under non-irrigation (W0, no irrigation during growth stage), one time irrigation (W1, irrigation applied at stem elongation) and two times irrigation (W2, irrigation applied at stem elongation and anthesis) conditions. Nearly 90% of cultivar mixture cropping treatments experienced an increase in grain yield as compared with the mean of the pure stands under W0, those for W1 and W2 were 80% and 85%, respectively. Over 75% of cultivar mixture cropping treatments got greater biomass than the mean of the pure stands under the three irrigation conditions. Cultivar mixture cropping cost more water than pure stands under W0 and W1, whereas the water consumption under W2 decreased by 5.9%-6.8% as compared with pure stands. Approximately 90% of cultivar mixtures showed an increase of 5.4% 34.5% in WUE as compared with the mean of the pure stands, and about 75% of cultivar mixtures had 0.8%-28.5% higher WUE than the better pure stands under W0. Similarly, there were a majority of mixture cropping treatments with higher WUE than the mean and the better one of the pure stands under W1 and W2. On the whole, proper cultivar mixture cropping could increase yield and WUE, and a higher increase in WUE occurred under limited irrigation condition. PMID- 27362566 TI - Practices for Identifying and Rejecting Hemolyzed Specimens in Europe. PMID- 27362565 TI - Estimated National Volume of Laboratory Results Affected by Hemolyzed Specimens From Emergency Departments. PMID- 27362567 TI - Updates on Surgical and Molecular Pathology Concerning Breast Diseases. PMID- 27362568 TI - Papillary Lesions of the Breast: An Update. AB - CONTEXT: -Papillary lesions of the breast, characterized by the presence of arborescent fibrovascular cores that support epithelial proliferation, constitute a heterogeneous group of neoplasms with overlapping clinical manifestation and histomorphologic features, but may have divergent biological behavior. These lesions are exclusively intraductal neoplasms, although an invasive carcinoma may rarely have a predominantly papillary architecture. Although recognition of a papillary architecture is typically not challenging, the histologic distinction of these entities is not always straightforward. Historically, different terminologies and variable criteria have been proposed for a given entity by various authorities. The difficulty in classifying these lesions has been further confounded by the scarcity of data and the heterogeneity across different studies with regard to the molecular genetic characteristics of this group of lesions. OBJECTIVE: -To provide an overview focusing on the current concepts in the diagnosis and classification of papillary lesions of the breast incorporating recent molecular genetic advances. DATA SOURCES: -Data were obtained from pertinent peer-reviewed English-language literature. CONCLUSIONS: -The recent evolution of molecular techniques has enhanced our knowledge of the pathogenesis of papillary carcinomas of the breast. This, along with emerging outcome studies, has led to prognosis-based reclassification of some of these entities. Additional studies focusing on the molecular signatures are needed to identify potential decision tools to further stratify these lesions with respect to prognostic significance. PMID- 27362569 TI - Pathologic Spectrum of Secretory and Mucinous Breast Lesions. AB - CONTEXT: -The morphologic spectrum of secretory breast lesions encompasses benign, borderline, and malignant lesions. They are characterized by luminal pink, proteinaceous secretions and variable degrees of cytologic atypia ranging from low grade to high grade, with frequent papillary formations. Other lesions, benign and malignant, can also show luminal and extraluminal secretions and share similar features with secretory lesions, making them diagnostically challenging. OBJECTIVE: -To discuss the differential diagnosis of secretory breast lesions, emphasizing the most important diagnostic features of benign and malignant lesions. Lesions with intraluminal secretions discussed at length in this review include pregnancy-like hyperplasia, cystic hypersecretory hyperplasia, collagenous spherulosis, microglandular adenosis, hypersecretory carcinoma, and secretory carcinoma. Lesions with extravasated mucin, such as mucocele-like lesions and mucinous carcinoma, are also briefly discussed. DATA SOURCES: Published articles obtained from a PubMed search of the English literature were the primary source for this review. CONCLUSIONS: -Lesions with secretory features described in this review show a pathologic spectrum, sometimes even within the same lesion. As a consequence, one should employ a low threshold for recommending reexcision on a core biopsy containing benign-appearing hypersecretory glands and use all ancillary data, including clinical presentation, imaging findings, morphology, immunohistochemistry, and molecular pathology, to render a final diagnosis. PMID- 27362570 TI - Small Glandular Proliferations of the Breast With Absent or Attenuated Myoepithelial Reactivity by Immunohistochemistry: A Review Focusing on the Differential Diagnosis and Interpretative Pitfalls. AB - CONTEXT: -Small glandular proliferations of the breast encompass a variety of benign, atypical, and malignant lesions that show some overlapping morphologic features. Myoepithelial stains are frequently used in the workup of these lesions in order to rule out or establish a diagnosis of invasive carcinoma. Some benign lesions show absent or diminished myoepithelial staining, and may represent an interpretative pitfall, particularly in small core biopsy samples. OBJECTIVE: -To review small glandular proliferations of the breast that show absent or diminished staining with myoepithelial immunohistochemical markers. DATA SOURCES: -The study comprised a review of published literature and clinical case material. CONCLUSIONS: -The interpretation of myoepithelial stains in small glandular proliferations of the breast can, on some occasions, represent a challenge in diagnosing these lesions. Recognition of the key histopathologic features and immunohistochemical staining patterns of the entities in the differential diagnosis is crucial in their workup. PMID- 27362571 TI - Phyllodes Tumor of the Breast: Histopathologic Features, Differential Diagnosis, and Molecular/Genetic Updates. AB - CONTEXT: -Phyllodes tumor (PT) of the breast is a rare fibroepithelial neoplasm with risks of local recurrence and uncommon metastases. The classification proposed by the World Health Organization for PTs into benign, borderline, and malignant is based on a combination of several histologic features. The differential diagnosis between PT and fibroadenoma and the histologic grading of PT remain challenging. In addition, the molecular pathogenesis of PT is largely unknown. OBJECTIVE: -To provide an updated overview of pathologic features, diagnostic terminology, and molecular alterations of PT. DATA SOURCES: -Current English literature related to PT of the breast. CONCLUSIONS: -Phyllodes tumor shows a wide spectrum of morphology. There are no clearly distinct boundaries between PT and fibroadenoma. Strict histologic assessment of a combination of histologic features with classification can help to achieve the correct diagnosis and provide useful clinical information. The genomic landscapes of PT generated from genomic sequencing provide insights into the molecular pathogenesis of PT and help to improve diagnostic accuracy and identify potential drug targets in malignant PT. PMID- 27362572 TI - Primary Neuroendocrine Tumors of the Ureter: A Short Review. AB - Neuroendocrine tumors represent 0.05% of urinary tract malignancies, and most originate in the bladder. Their pathogenesis is debated, since ureters are thought to lack neuroendocrine cells. Morphologically, most ureteral neuroendocrine tumors demonstrate the typical small cell neuroendocrine appearance, are immunohistochemically positive for synaptophysin/chromogranin A/CD56, and show electron-dense granules by electron microscopy. Clinical presentation is similar to that of other more common ureteral neoplasms. Prognosis is usually dismal, but a multimodal treatment approach including platinum-based adjuvant or neoadjuvant chemotherapy seems to be beneficial. PMID- 27362573 TI - Epstein-Barr Virus-Associated Smooth Muscle Tumor. AB - Immunodeficient individuals are prone to develop a number of opportunistic infections and unique neoplasms. Epstein-Barr virus-associated smooth muscle tumor is an uncommon neoplasm associated with immunodeficiency. It has been described in patients infected with human immunodeficiency virus, in the posttransplant setting, and in those with congenital immunodeficiency. Different anatomic sites can be involved by Epstein-Barr virus-associated smooth muscle tumor, and even multiple locations can contain these unique lesions within the same patient. The presence of variable numbers of intratumoral lymphocytes and primitive round cell areas are the unique defining features for this tumor. Histopathologic features may vary considerably in terms of cellular atypia, mitotic activity, and necrosis, with no correlation to the clinical behavior. Demonstration of Epstein-Barr virus infection by in situ hybridization within tumor cell remains critical for the diagnosis. The mechanism for Epstein-Barr virus infection of progenitor cells and neoplastic transformation has been an area of interest and conjecture. Different treatment strategies are proposed according to underlying disease status. This paper reviews the clinicopathologic features of this uncommon neoplasm with detailed discussion of the role of Epstein-Barr virus in the pathogenesis. PMID- 27362574 TI - Effects of pathogens on sensory-mediated interactions between plants and insect vectors. AB - Vector-borne plant pathogens frequently alter host-plant quality and associated plant cues in ways that influence vector recruitment and pathogen acquisition. Furthermore, following acquisition by the vector, pathogens may influence subsequent vector behavior either directly or via effects on the host plant. Given that such effects have significant implications for pathogen acquisition and inoculation, selection might be expected to favor patterns of pathogen effects on host-vector interactions that are conducive to transmission. Consequently, we might also expect to observe broad similarity in the effects of pathogens sharing similar modes of transmission. Here we discuss some specific hypotheses arising from these expectations and the implications of recent empirical findings. On the whole, this evidence is consistent with the expectation that pathogen effects on host-vector interactions are often (though not always) adaptive with respect to transmission. PMID- 27362576 TI - Long-term results of the monocusp valve formation in the common femoral vein in patients with avalvular deep veins of the lower extremities. AB - BACKGROUND: Aim of the study was to evaluate the long-term results of the monocusp valve formation in the common femoral vein (CFV) in patients with avalvular deep veins (ADV) of the lower extremities. METHODS: A total of 36 patients (24 women and 12 men) at the age varying from 37 to 58 years old were given surgical treatment during the period from 2008 to 2014. Six patients presented with congenital ADV, while the remaining 30 ADV had a consequence of the post-thrombotic lesion in the valves with the complete recanalization and manifested deep venous axial reflux. In terms of CEAP clinical classification, the patients were categorized into the following groups: S4b (N.=11), C5 (N.=18), C6 (N.=7). All the patients underwent Duplex ultrasound (DUS) examination. Twelve patients were additionally examined by venography. Kistner grade IV reflux was diagnosed in all the patients. Twenty-eight patients had undergone surgical interventions on superficial and perforating veins before. The severe (C4b-C6) forms of chronic venous disease with manifested axial reflux in deep veins were regarded as an indication for surgery in the patients refractory to traditional treatment. The method described by Opie et al. was employed to construct the monocusp venous valve in the CFV. RESULTS: The long-term results of the treatment were evaluated in 26 patients followed up during the period from 18 to 48 (mean 29.5+/-8.2) months. Cumulative clinical success rate at four years was 76.5%. Freedom from ulcer recurrence at four years was 83.4% (C6 patients). Cumulative competence rate of the neovalve was accomplished in 70.6%. The evaluation in two years based on the VCSS revealed the reduction in the severity of the manifestations of chronic venous insufficiency (P<0.01). The quality of life was improved, its index decreased from 60.6+/-18.7 to 40.7+/-12.8 (P<0.05). The circumference of the narrowest segment of the tibia decreased from 271.1+/-4.7 to 256.8+/-5.7 mm (P<0.05). CONCLUSIONS: Formation of the monocusp valve in CFV makes it possible to eliminate pathological blood reflux from the inferior vena cava to deep veins of the lower extremities that is known to be one of the main factors in the appearance and progression of chronic venous insufficiency (CVI). The high effectiveness of this operation is confirmed by the well apparent clinical improvement in the state of the affected lower extremity and the quality of life of the patients. PMID- 27362575 TI - Adipose-derived stem cells sustain prolonged angiogenesis through leptin secretion. AB - Recent studies suggest that adipose-derived stem cells (ASCs) play a role in tissue remodeling through the release of cytokines and growth factors. We compared the secreted cytokine profile of hypoxia-conditioned ASCs (hASCs) with normoxic ASCs (nASCs) and we analyzed the effect of ASCs conditioned medium (CM) on endothelial cells. We found that hypoxia induced a transient upregulation of VEGF in ASCs and a notable and enduring upregulation of leptin mRNA expression 30 fold greater than control after 24 h and up to 60-fold greater than control at day 7. CM from hASC stimulated EC tube formation to a significantly greater extent than CM from nASC. This might be due to leptin-secreted factor. Indeed, exogenous leptin stimulated the expression of HIF2-alpha, but not HIF1-alpha, and upregulated the expression of Flt-1 and Tie-1 proangiogenic receptors. In conclusion, hASCs may be particularly efficient in sustaining angiogenesis through the release of leptin. PMID- 27362577 TI - Efficacy and safety of Duplex-guided polidocanol foam sclerotherapy for venous malformations. AB - BACKGROUND: The aim of our study was to report our experience regarding the safety, efficacy of duplex-guided polidocanol (POL) foam sclerotherapy on the overall status of signs and symptoms in patients with venous malformations (VMs). METHODS: Thirty seven patients with symptomatic extratruncular VMs were treated with duplex-guided POL foam sclerotherapy using Tessari's method. Twenty five patients had limited VMs, while twelve had infiltrating VMs. Postsclerotherapy surveillance was done 6 months after the last sclerotherapy session and comprised both clinical and duplex evaluation. Clinical evaluation entailed a patient self assessment questionnaire using a four-point scale to rate the degree of symptoms improvement as follows: disappeared, decreased, worsened, or recurred. Findings obtained by duplex scanning were divided into four groups: 1) disappeared group; 2) partially recanalized group; 3) totally recanalized group; and 4) worsened group. RESULTS: There were 20 males and 17 females with mean age of 22.8+/-5.5 years. There was a significant reduction in the total amount of POL (P=0.0037), the number of sclerotherapy sessions was significantly lesser (P=0.0019), and treatment success was significantly higher (P=0.0495) in patients with limited VMs in comparison to those with infiltrating VMs. No major complications related to sclerotherapy were encountered in both groups. CONCLUSIONS: Polidocanol foam sclerotherapy is effective, and safe for treatment of VMs, with high success rate and low risk of major complications. Although associated with relatively high recurrence rate compared with ethanol sclerotherapy, this can be overcome by additional treatment sessions, given the relative simplicity, speed, and safety. PMID- 27362579 TI - Selective plasticity of hippocampal GABAergic interneuron populations following kindling of different brain regions. AB - The vulnerability and plasticity of hippocampal GABAergic interneurons is a topic of broad interest and debate in the field of epilepsy. In this experiment, we used the electrical kindling model of epilepsy to determine whether seizures that originate in different brain regions have differential effects on hippocampal interneuron subpopulations. Long-Evans rats received 99 electrical stimulations of the hippocampus, amygdala, or caudate nucleus, followed by sacrifice and immunohistochemical or western blot analyses. We analyzed markers of dendritic (somatostatin), perisomatic (parvalbumin), and interneuron-selective (calretinin) inhibition, as well as an overall indicator (GAD67) of interneuron distribution across all major hippocampal subfields. Our results indicate that kindling produces selective effects on the number and morphology of different functional classes of GABAergic interneurons. In particular, limbic kindling appears to enhance dendritic inhibition, indicated by a greater number of somatostatin immunoreactive (-ir) cells in the CA1 pyramidal layer and robust morphological sprouting in the dentate gyrus. We also found a reduction in the number of interneuron-selective calretinin-ir cells in the dentate gyrus of hippocampal kindled rats, which suggests a possible reduction of synchronized dendritic inhibition. In contrast, perisomatic inhibition indicated by parvalbumin immunoreactivity appears to be largely resilient to the effects of kindling. Finally, we found a significant induction in the number of GAD67-cells in caudate kindled rats in the dentate gyrus and CA3 hippocampal subfields. Taken together, our results demonstrate that kindling has subfield-selective effects on the different functional classes of hippocampal GABAergic interneurons. J. Comp. Neurol. 525:389-406, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27362580 TI - Toxicity, pharmacokinetics, and in vivo efficacy of biotinylated chitosan surface modified PLGA nanoparticles for tumor therapy. AB - Based on our previous work on the PLGA nanoparticles modified with biotinylated chitosan (Bio-CS-PLGA NPs), we further studied the stability, toxicity, pharmacokinetics, and in vivo efficacy. The safety of NPs was studied through single-dose toxicity test in mice, and the result showed that NPs were well tolerated at the dose of 300 mg/kg. Compared with the free EPB group, the NPs group exhibited higher plasma drug concentration, longer half-life time. EPB loaded NPs significantly inhibited the tumor growth compared to free EPB. All results suggested that Bio-CS-PLGA NPs were stable, safe, and showed a promising potential on targeted drug delivery. PMID- 27362581 TI - Are the Poor Dying Younger in Malaysia? An Examination of the Socioeconomic Gradient in Mortality. AB - INTRODUCTION: Socioeconomic inequalities in health represent unfairness in the health distribution of a population. Efforts to produce information on mortality distributions in many low and middle income countries (LMICs) are mostly hampered by lack of data disaggregated by socioeconomic groups. In this paper we describe how mortality statistics obtained from multiple data sources were combined to provide an evaluation of the socioeconomic distribution of mortality in Malaysia, a LMIC located in the Asia Pacific region. METHODS: This study has an ecological design. As a measure of socioeconomic status, we used principal component analysis to construct a socioeconomic index using census data. Districts were ranked according to the standardised median index of households and assigned to each individual in the 5-year mortality data. The mortality indicators of interest were potential years of life lost (PYLL), standardised mortality ratio (SMR), infant mortality rate (IMR) and under-5 mortality rate (U5MR). Both socioeconomic status and mortality outcomes were used compute the concentration index which provided the summary measure of the magnitude of inequality. RESULTS: Socially disadvantaged districts were found to have worse mortality outcomes compared to more advantaged districts. The values of the concentration index for the overall population of the Peninsula are C = -0.1334 (95% CI: -0.1605 to 0.1063) for the PYLL, C = -0.0685 (95% CI: -0.0928 to -0.0441) for the SMR, C = 0.0997 (95% CI: -0.1343 to -0.0652) for the IMR and C = -0.1207 (95% CI: -0.1523 to -0.0891) for the U5MR. Mortality outcomes within ethnic groups were also found to be less favourable among the poor. CONCLUSION: The findings of this study suggest that socioeconomic inequalities disfavouring the poor exist in Malaysia. PMID- 27362583 TI - Primary mechanical factors contributing to foot eversion moment during the stance phase of running. AB - Rearfoot external eversion moments due to ground reaction forces (GRF) during running have been suggested to contribute to overuse running injuries. This study aimed to identify primary factors inducing these rearfoot external eversion moments. Fourteen healthy men ran barefoot across a force plate embedded in the middle of 30-m runway with 3.30 +/- 0.17 m . s-1. Total rearfoot external eversion/inversion moments (Mtot) were broken down into the component Mxy due to medio-lateral GRF (Fxy) and the component Mz due to vertical GRF (Fz). Ankle joint centre height and medio-lateral distance from the centre of pressure to the ankle joint centre (a_cop) were calculated as the moment arm of these moments. Mxy dominated Mtot just after heel contact, with the magnitude strongly dependent on Fxy, which was most likely caused by the medio-lateral foot velocity before heel contact. Mz then became the main generator of Mtot throughout the first half of the stance phase, during which a_cop was the critical factor influencing the magnitude. Medio-lateral foot velocity before heel contact and medio-lateral distance from the centre of pressure to the ankle joint centre throughout the first half of the stance phase were identified as primary factors inducing the rearfoot external eversion moment. PMID- 27362584 TI - Transforming a municipal school sports programme through a critical communicative methodology: The role of the of advisory committee. AB - This research applies a communicative methodology (CM) to the transformation and improvement of the Municipal Comprehensive School Sports Programme in Segovia, Spain (MCSSP), using egalitarian dialogue, based on validity rather than power claims to achieve intersubjectivity and arrive at consensus between all of the Programme's stakeholders through the intervention of an advisory committee (AC). The AC is a body comprising representatives of all stakeholder groups involved in the programme. During the 2013-2014 academic year the programme's AC met four times, operating as a communicative focus group (CFG). The meetings focused on: (1) excluding dimensions (barriers preventing transformation) and transforming dimensions (ways of overcoming barriers), (2) the programme's strengths, (3) the programme's weaknesses and specific actions to remedy them, and (4) the resulting conclusions which were then incorporated into the subsequent programme contract signed between the University and the Segovia Local Authority for 2014-2018. The key conclusions were: (1) the recommendations of the AC widen the range of perspectives and help the research team to make key decisions and (2) the use of CM to fully evaluate the programme and to reach a consensus on how to improve it proved very valuable. PMID- 27362585 TI - Non-Contrast Renal Magnetic Resonance Imaging to Assess Perfusion and Corticomedullary Differentiation in Health and Chronic Kidney Disease. AB - AIMS: Arterial spin labelling (ASL) MRI measures perfusion without administration of contrast agent. While ASL has been validated in animals and healthy volunteers (HVs), application to chronic kidney disease (CKD) has been limited. We investigated the utility of ASL MRI in patients with CKD. METHODS: We studied renal perfusion in 24 HVs and 17 patients with CKD (age 22-77 years, 40% male) using ASL MRI at 3.0T. Kidney function was determined using estimated glomerular filtration rate (eGFR). T1 relaxation time was measured using modified look locker inversion and xFB02;ow-sensitive alternating inversion recovery true-fast imaging and steady precession was performed to measure cortical and whole kidney perfusion. RESULTS: T1 was higher in CKD within cortex and whole kidney, and there was association between T1 time and eGFR. No association was seen between kidney size and volume and either T1, or ASL perfusion. Perfusion was lower in CKD in cortex (136 +/- 37 vs. 279 +/- 69 ml/min/100 g; p < 0.001) and whole kidney (146 +/- 24 vs. 221 +/- 38 ml/min/100 g; p < 0.001). There was significant, negative, association between T1 longitudinal relaxation time and ASL perfusion in both the cortex (r = -0.75, p < 0.001) and whole kidney (r = 0.50, p < 0.001). There was correlation between eGFR and both cortical (r = 0.73, p < 0.01) and whole kidney (r = 0.69, p < 0.01) perfusion. CONCLUSIONS: Significant differences in renal structure and function were demonstrated using ASL MRI. T1 may be representative of structural changes associated with CKD; however, further investigation is required into the pathological correlates of reduced ASL perfusion and increased T1 time in CKD. PMID- 27362587 TI - Medial gastrocnemius muscle-tendon interaction and architecture change during exhaustive hopping exercise. AB - BACKGROUND: Previous literature has shown in vivo changes in muscle-tendon interaction during exhaustive stretch-shortening cycle (SSC) exercise. It is unclear whether these changes in muscle-tendon length during exhaustive SSC exercise are associated with changes in mechanical efficiency (ME). The purpose of the study was to investigate whether changes in platarflexor contractile component (CC) length, tendon length, and changes in plantarflexor muscle activity could explain reduction in ME during exhaustive SSC exercise. METHODS: Eight males participated in an exhaustive hopping task to fatigue. Mechanical work and energy expenditure were calculated at different time-points during the hopping task. Furthermore, hopping kinetics and kinematics, medial gastrocnemius (MG) muscle activity, and in vivo ultrasound of the MG were also collected at different time-points throughout the hopping task. RESULTS: ME did not change during the hopping protocol despite shorter tendon and longer CC lengths as subjects approached exhaustion. Percent decreases in pennation angle and muscle thickness were most strongly correlated to time to exhaustion (r=0.94, p?0.05; r=0.87, p?0.05; respectively). Percent changes in CC length change and pennation angle were strongly correlated to percent decrease in maximal voluntary isometric plantarflexion (MVIP) force (r=-0.71, p?0.04; r=0.70, p?0.05; respectively). Braking/push-off EMG ratio increased from initial pre-fatigue values to all other time points showing neuromuscular adaptations to altered muscle lengths. CONCLUSION: Findings from the current study suggest that changes in CC and tendon lengths occur during repetitive hopping to exhaustion, with the amount change strongly related to time to exhaustion. ME of hopping remained unchanged in the presence of altered CC and tendon lengths. PMID- 27362588 TI - Health-Enabling and Ambient Assistive Technologies: Past, Present, Future. AB - BACKGROUND: During the last decades, health-enabling and ambient assistive technologies became of considerable relevance for new informatics-based forms of diagnosis, prevention, and therapy. OBJECTIVES: To describe the state of the art of health-enabling and ambient assistive technologies in 1992 and today, and its evolution over the last 25 years as well as to project where the field is expected to be in the next 25 years. In the context of this review, we define health-enabling and ambient assistive technologies as ambiently used sensor-based information and communication technologies, aiming at contributing to a person's health and health care as well as to her or his quality of life. METHODS: Systematic review of all original articles with research focus in all volumes of the IMIA Yearbook of Medical Informatics. Surveying authors independently on key projects and visions as well as on their lessons learned in the context of health enabling and ambient assistive technologies and summarizing their answers. Surveying authors independently on their expectations for the future and summarizing their answers. RESULTS: IMIA Yearbook papers containing statements on health-enabling and ambient assistive technologies appear first in 2002. These papers form a minor part of published research articles in medical informatics. However, during recent years the number of articles published has increased significantly. Key projects were identified. There was a clear progress on the use of technologies. However proof of diagnostic relevance and therapeutic efficacy remains still limited. Reforming health care processes and focussing more on patient needs are required. CONCLUSIONS: Health-enabling and ambient assistive technologies remain an important field for future health care and for interdisciplinary research. More and more publications assume that a person's home and their interaction therein, are becoming important components in health care provision, assessment, and management. PMID- 27362589 TI - Clinical Information Systems - From Yesterday to Tomorrow. AB - OBJECTIVES: To review the history of clinical information systems over the past twenty-five years and project anticipated changes to those systems over the next twenty-five years. METHODS: Over 250 Medline references about clinical information systems, quality of patient care, and patient safety were reviewed. Books, Web resources, and the author's personal experience with developing the HELP system were also used. RESULTS: There have been dramatic improvements in the use and acceptance of clinical computing systems and Electronic Health Records (EHRs), especially in the United States. Although there are still challenges with the implementation of such systems, the rate of progress has been remarkable. Over the next twenty-five years, there will remain many important opportunities and challenges. These opportunities include understanding complex clinical computing issues that must be studied, understood and optimized. Dramatic improvements in quality of care and patient safety must be anticipated as a result of the use of clinical information systems. These improvements will result from a closer involvement of clinical informaticians in the optimization of patient care processes. CONCLUSIONS: Clinical information systems and computerized clinical decision support have made contributions to medicine in the past. Therefore, by using better medical knowledge, optimized clinical information systems, and computerized clinical decision, we will enable dramatic improvements in both the quality and safety of patient care in the next twenty five years. PMID- 27362591 TI - Visualization of the IMIA Yearbook of Medical Informatics Publications over the Last 25 Years. AB - BACKGROUND: The last 25 years have been a period of innovation in the area of medical informatics. The International Medical Informatics Association (IMIA) has published, every year for the last quarter century, the Yearbook of Medical Informatics, collating selected papers from various journals in an attempt to provide a summary of the academic medical informatics literature. The objective of this paper is to visualize the evolution of the medical informatics field over the last 25 years according to the frequency of word occurrences in the papers published in the IMIA Yearbook of Medical Informatics. METHODS: A literature review was conducted examining the IMIA Yearbook of Medical Informatics between 1992 and 2015. These references were collated into a reference manager application to examine the literature using keyword searches, word clouds, and topic clustering. The data was considered in its entirety, as well as segregated into 3 time periods to examine the evolution of main trends over time. Several methods were used, including word clouds, cluster maps, and custom developed web based information dashboards. RESULTS: The literature search resulted in a total of 1210 references published in the Yearbook, of which 213 references were excluded, resulting in 997 references for visualization. Overall, we found that publications were more technical and methods-oriented between 1992 and 1999; more clinically and patient-oriented between 2000 and 2009; and noted the emergence of "big data", decision support, and global health in the past decade between 2010 and 2015. Dashboards were additionally created to show individual reference data, as well as, aggregated information. CONCLUSION: Medical informatics is a vast and expanding area with new methods and technologies being researched, implemented, and evaluated. Determining visualization approaches that enhance our understanding of literature is an active area of research, and like medical informatics, is constantly evolving as new software and algorithms are developed. This paper examined several approaches for visualizing the medical informatics literature to show historical trends, associations, and aggregated summarized information to illustrate the state and changes in the IMIA Yearbook publications over the last quarter century. PMID- 27362590 TI - Imaging Informatics: 25 Years of Progress. AB - The science and applications of informatics in medical imaging have advanced dramatically in the past 25 years. This article provides a selective overview of key developments in medical imaging informatics. Advances in standards and technologies for compression and transmission of digital images have enabled Picture Archiving and Communications Systems (PACS) and teleradiology. Research in speech recognition, structured reporting, ontologies, and natural language processing has improved the ability to generate and analyze the reports of imaging procedures. Informatics has provided tools to address workflow and ergonomic issues engendered by the growing volume of medical image information. Research in computeraided detection and diagnosis of abnormalities in medical images has opened new avenues to improve patient care. The growing number of medical-imaging examinations and their large volumes of information create a natural platform for "big data" analytics, particularly when joined with high dimensional genomic data. Radiogenomics investigates relationships between a disease's genetic and gene-expression characteristics and its imaging phenotype; this emerging field promises to help us better understand disease biology, prognosis, and treatment options. The next 25 years offer remarkable opportunities for informatics and medical imaging together to lead to further advances in both disciplines and to improve health. PMID- 27362592 TI - Impact of Frailty and Other Geriatric Syndromes on Clinical Management and Outcomes in Elderly Patients With Non-ST-Segment Elevation Acute Coronary Syndromes: Rationale and Design of the LONGEVO-SCA Registry. AB - The incidence of acute coronary syndromes (ACS) is high in the elderly. Despite a high prevalence of frailty and other aging-related variables, little information exists about the optimal clinical management in patients with coexisting geriatric syndromes. The aim of the LONGEVO-SCA registry (Impacto de la Fragilidad y Otros Sindromes Geriatricos en el Manejo y Pronostico Vital del Anciano con Sindrome Coronario Agudo sin Elevacion de Segmento ST) is to assess the impact of aging-related variables on clinical management, prognosis, and functional status in elderly patients with ACS. A series of 500 consecutive octogenarian patients with non-ST-segment elevation ACS from 57 centers in Spain will be included. A comprehensive geriatric assessment will be performed during the admission, assessing functional status (Barthel Index, Lawton-Brody Index), frailty (FRAIL scale, Short Physical Performance Battery), comorbidity (Charlson Index), nutritional status (Mini Nutritional Assessment-Short Form), and quality of life (Seattle Angina Questionnaire). Patients will be managed according to current recommendations. The primary outcome will be the description of mortality and its causes at 6 months. Secondary outcomes will be changes in functional status and quality of life. Results from this study might significantly improve the knowledge about the impact of aging-related variables on management and outcomes of elderly patients with ACS. Clinical management of these patients has become a major health care problem due to the growing incidence of ACS in the elderly and its particularities. PMID- 27362593 TI - Ethnic inequalities in stroke: improvements not fast enough for everyone. PMID- 27362594 TI - Are ethnic inequalities in 30-day ischaemic stroke survival emerging as treatment becomes more effective? AB - AIM: Studies of ethnic differences in stroke survival have produced inconsistent findings. As treatment becomes more effective, inequalities may increase. We examine time trends in ischaemic stroke case fatality in New Zealand. METHOD: The 30-day case fatality rate (CFR) of ischaemic stroke in New Zealand was calculated from routinely collected data for two 5-year periods (2000-2004 and 2010-2014) in Maori, Pacific, Asian and European people. A Poisson regression model tested ethnic inequalities between Europeans and people of other ethnicities in each time period. RESULTS: From 2000-2004 to 2010-2014, the age-sex standardised CFR in Europeans fell from 13.4% (95% CI 13.0 to 13.9%) to 10.7% (10.3 to 11.1%). In Pacific and Asian people, the CFR rose between the two periods, and in Maori there was a drop from 18.2% to 16.2%; neither of these differences were statistically significant. After controlling for socio-demographic variables, service factors and comorbidities, the CFR was higher for Maori than Europeans in 2000-2004, and for all ethnic groups compared with Europeans in 2010-2014. CFR ethnic inequality rose over that time-the change being statistically significant for Pacific (p=0.033) and Asian (p=0.010), and of borderline significance for Maori (p=0.053). CONCLUSIONS: Ethnic inequalities in 30-day ischaemic stroke survival have increased significantly in the last 10 years. This may be due to differences in severity at presentation, or in access and utilisation of the increasingly effective acute and hyper-acute stroke interventions. PMID- 27362595 TI - Auckland City Hospital's Ortho-Geriatric Service: an audit of patients aged over 65 with fractured neck of femur. AB - AIMS: The aims of this audit were to collect the Minimum Data Set outlined by the Australia New Zealand Hip Fracture Registry (ANZHFR), assess patient characteristics, analyse process of care, and evaluate how this compares to NICE guidelines for hip fracture care, as well as to Auckland Hospital data from 2007. METHOD: Retrospective case record audit of patients with fractured neck of femur aged 65 years and over admitted under Orthopaedics over a 4-month period in 2013. RESULTS: Ninety-one patients were audited; mean age was 83 years, 68% were female. Both inpatient and 30-day mortality was 5%. 120-day mortality was 15%. Seventy-six percent of patients were admitted from ED within the national health target prescribed period of 6 hours. Only one patient was treated non-surgically. Eighty-six percent had surgery within 48 hours of admission. Eighty-two percent of patients had rehabilitation and treatment by Older People's Health. Of those living at home pre-fracture, 76% returned home on discharge. Thirty-seven percent of patients were able to walk unaided prior to hip fracture, but only 1% on discharge. Average overall length of stay was 22 days. Bisphosphonates were prescribed for 56% of patients. CONCLUSIONS: Compared to 2007, Auckland City Hospital has demonstrated a significant improvement in the rate of provision of timely surgery for hip fracture patients. Most patients are receiving the guideline recommended fracture-specific surgical interventions. The assessment and treatment of osteoporosis needs further attention. PMID- 27362596 TI - Incidence and type of bleeding complications early and late after acute coronary syndrome admission in a New Zealand cohort (ANZACS-QI-7). AB - AIMS: Use of anti-thrombotic agents has reduced ischaemic events in acute coronary syndromes (ACS), but can increase the risk of bleeding. Identifying bleeding events using a consistent methodology from routinely collected national datasets would be useful. Our aims were to describe the incidence and types of bleeding in-hospital and post-discharge in the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) cohort. METHODS: 3,666 consecutive patients admitted with ACS (2007-2010) were identified within the ANZACS-QI registry. A set of International Classification of Disease 10 (ICD-10) codes that identified bleeding events was developed. Anonymised linkage to national mortality and hospitalisation datasets was used to identify these bleeding events at the index admission and post-discharge. RESULTS: Three hundred and ninety-nine (10.8%) out of 3,666 patients had at least one bleeding event during a mean follow-up of 1.94 years. One hundred and sixty-one (4.4%) had a bleeding event during their index admission, and 271 (7.4%) patients were re-hospitalised with bleeding during follow-up. Sixty-one patients (37.9%) were transfused for bleeding in the index admission cohort, and 59 patients (21.8%) at a subsequent admission. Procedural bleeding was the most common event during the index admission, whereas gastrointestinal bleeding was the most common delayed bleeding presentation. CONCLUSION: One in ten ACS patients experienced a significant bleeding event within 2 years. The use of this ICD-10 bleeding definition in national ACS cohorts will facilitate the study of bleeding event incidence and type over time and between geographical regions, both nationally and internationally, and the impact of changes in anti-thrombotic therapy and interventional practice. PMID- 27362597 TI - Impact of PET-CT scan on management in upper gastrointestinal malignancy. AB - INTRODUCTION: Curative treatments of upper gastrointestinal (UGI) cancers carry significant morbidity and mortality. Therefore, accurate pre-treatment staging is important. PET-CT scan is an expensive modality, and not readily available in New Zealand. The aim of this study was to describe how PET-CT scan influences management in UGI cancer. METHODS: This retrospective descriptive study included patients with UGI cancer with no evidence of metastatic disease on IV contrast CT scan, and those medically fit for curative treatment. Patients then underwent PET CT scan. We defined influence or change in management if PET-CT showed metastatic disease or other lesions requiring further investigation. RESULTS: Seventy-nine patients were identified for the purposes of this study. Fifty-nine (74.7%) had CT scan showing no evidence of metastatic disease. Of these, PET-CT scan influenced management in 14 patients (23.7%) and found distant metastasis in eight patients (13.6%). The remaining 20 of 79 patients (25.3%) had CT scan showing indeterminate lesions. Of these, PET-CT scan influenced management in eight patients (40%), with metastatic disease seen in seven patients (35%). CONCLUSION: Our study confirms the value of PET-CT scan in pre-operative staging of UGI cancer. It had a greater impact on patients with intermediate lesions on staging CT. PMID- 27362598 TI - Development and initial outcomes of an upper gastrointestinal multidisciplinary clinic. AB - INTRODUCTION: Patients with upper gastrointestinal cancer are often comorbid and require complex surgical treatments for their cancers, meaning that their preoperative assessment can be based around numerous outpatient assessments with multiple services. A multidisciplinary clinic (MDC) was developed for the assessment of patients with confirmed or suspected upper gastrointestinal cancers. METHODS: Face-to-face meetings were held between stakeholder services at Waitemata District Health Board, and clinic resource allocated. Significant IT modification of existing clinic booking software was required. RESULTS: Between September 2014, and September 2015, there were a total of 165 new patient, and 710 follow-up appointments. All new patients were seen by a surgeon and then other specialties. Of the 165 new patient appointments, 146 (88%) patients had a definitive treatment plan in place and were cleared by anaesthesia and intensive care at the end of the clinic. Staff and patients report high levels of satisfaction for the clinic. CONCLUSION: A dedicated MDC has provided a single forum where complex patients can be reviewed, and a definitive treatment plan formulated in nearly 90% of patients, even when this involves multiple medical and paramedical specialties with high levels of patient and clinician satisfaction. PMID- 27362599 TI - Treatment of uncomplicated cystitis: analysis of prescribing in New Zealand. AB - AIMS: To describe prescribing for women with suspected urinary tract infections, including suspected uncomplicated cystitis, in New Zealand. METHODS: Randomly selected community pharmacies participated in the study. Women attending the pharmacy in a 2-week period in 2012 for prescribed or non-prescription treatment of symptoms suggesting a urinary tract infection, or prophylaxis of a urinary tract infection, were invited to self-complete a questionnaire. Analysis focused on prescribing for women with symptoms of cystitis without complicating features. RESULTS: Valid questionnaires arising from a prescription treatment were received from 789 patients from 139 pharmacies. Questionnaire data indicated that 17% of women had symptoms of cystitis without complicating features. Most prescribing was for a first-line agent, trimethoprim (59%) or nitrofurantoin (14%), but norfloxacin was also common (21%). Women with self-reported antibiotic use for suspected cystitis in the past 6 months were more likely to be prescribed norfloxacin than those with no such use. Many prescriptions were for a dose or duration outside those recommended in New Zealand guidelines. CONCLUSIONS: While use of first-line agents is generally high, norfloxacin use could be reduced further. There is scope to understand clinical practice that deviates from guideline use regarding dose and duration. PMID- 27362600 TI - New Zealand needs guidelines for the safe and responsible inclusion of pregnant women in medical research. AB - Pregnancy is a crucial window of time that influences long-term population health. As a matter of justice, pregnant woman are entitled to high quality, evidenced-based care. As a matter of population health, we need to better understand foetal development, particularly the impact of lifestyle, stress, chronic conditions and clinical treatment during pregnancy. Pregnancy continues to be dominated by the precautionary principle, advocating for the routine exclusion of pregnant women from medical research, particularly intervention studies, on the grounds of foetal vulnerability. But this stance simply shifts the risk into the community. Due to a lack of evidence-based data, many pregnant women are refused medically important drugs, are subject to dangerous delays in getting drugs, or are prescribed drugs that are thought 'safe', despite evidence of possible teratogenicity. I argue that New Zealand needs to shift to a default position of inclusion of pregnant women in research; and to develop guidelines to facilitate their safe and responsible inclusion. The uniqueness of pregnancy gives rise to specific questions regarding research ethics. These questions warrant focused debate and the answers cannot simply be deduced from the general principles of research ethics we currently have in New Zealand. PMID- 27362601 TI - Doris Gordon: foundation of a legacy. AB - Doris Gordon Memorial Oration delivered to RANZCOG Annual Meeting, Wellington, 2 October, 2015. PMID- 27362603 TI - Intercalated degrees in New Zealand: a call for more undergraduate medical research training opportunities. PMID- 27362602 TI - Adult idiopathic hypertrophic pyloric stenosis. PMID- 27362604 TI - Conjunctival mucinous adenocarcinoma in an ostrich (Struthio camelus). AB - A 2-year-old male ostrich (Struthio camelus) presented with a rapidly growing soft tissue mass protruding from the ventromedial aspect of the right eye (OD). The initial physical examination revealed a soft tissue mass attached to the medial inferior conjunctiva. The mass was excised with cryosurgery, and the conjunctival tissue margins were treated with cryoablation. Histopathological examination diagnosed granulomatous inflammation associated with scattered acid fast bacteria. The ostrich recovered uneventfully and appeared healthy until recurrence of a grossly similar mass 2 months later. Gross examination revealed a botryoid mass attached to the inferior palpebral conjunctiva and extending onto the palpebral aspect of the nictitating membrane. Euthanasia was selected, and the histological diagnosis of the second mass was a mixed mucinous adenocarcinoma; however, no acid-fast bacteria were seen. Granulomatous conjunctival lesions have been previously described in the ostrich, while, to the authors' knowledge, neoplastic conjunctival lesions have not. Neoplasia should be considered as a differential diagnosis for a rapidly recurring, granulomatous conjunctival mass in this species. PMID- 27362605 TI - Eruptive Facial Postinflammatory Lentigo: Clinical and Dermatoscopic Features. AB - The face has not been considered a common site of fixed drug eruption, and the authors lack dermatoscopic studies of this condition on the subject. The authors sought to characterize clinical and dermatoscopic features of 8 cases of an eruptive facial postinflammatory lentigo. The authors conducted a retrospective review of 8 cases with similar clinical and dermatoscopic findings seen from 2 medical centers in 2 countries during 2010-2014. A total of 8 patients (2 males and 6 females) with ages that ranged from 34 to 62 years (mean: 48) presented an abrupt onset of a single facial brown-pink macule, generally asymmetrical, with an average size of 1.9 cm. after ingestion of a nonsteroidal antiinflammatory drugs that lasted for several months. Dermatoscopy mainly showed a pseudonetwork or uniform areas of brown pigmentation, brown or blue-gray dots, red dots and/or telangiectatic vessels. In the epidermis, histopathology showed a mild hydropic degeneration and focal melanin hyperpigmentation. Melanin can be found freely in the dermis or laden in macrophages along with a mild perivascular mononuclear infiltrate. The authors describe eruptive facial postinflammatory lentigo as a new variant of a fixed drug eruption on the face. PMID- 27362608 TI - QuickStats: Age-Adjusted Death Rates* for Females Aged 15-44 Years, by the Five Leading Causes of Death(?) - United States, 1999 and 2014. AB - The age-adjusted death rate for females aged 15-44 years was 5% lower in 2014 (82.1 per 100,000 population) than in 1999 (86.5). Among the five leading causes of death, the age-adjusted rates of three were lower in 2014 than in 1999: cancer (from 19.6 to 15.3, a 22% decline), heart disease (8.9 to 8.2, an 8% decline), and homicide (4.2 to 2.8, a 33% decline). The age-adjusted death rates for two of the five causes were higher in 2014 than in 1999: unintentional injuries (from 17.0 to 20.1, an 18% increase) and suicide (4.8 to 6.5, a 35% increase). Unintentional injuries replaced cancer as the leading cause of death in this demographic group. PMID- 27362607 TI - A patient with Temple syndrome satisfying the clinical diagnostic criteria of Silver-Russell syndrome. PMID- 27362609 TI - Websites Related to Volume 30, Issue 3. PMID- 27362611 TI - Variation in circulating antimullerian hormone precursor during the periovulatory and acute postovulatory phases of the human ovarian cycle. AB - OBJECTIVE: To determine whether the relative quantity of circulating AMH precursor (proAMH) declines relative to levels of the active form (AMHN,C) in the periovulatory phase of the ovarian cycle. DESIGN: Longitudinal study. SETTING: Local community. PATIENT(S): Sixteen women aged between 18 to 30 years with regular menstrual cycles between 25 to 35 days long. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serum concentrations of proAMH and total AMH (proAMH and AMHN,C combined) measured by immunoassay, with relative levels of proAMH expressed as the AMH prohormone index (API = [ProAMH]/[Total AMH] * 100). RESULT(S): The mean API in the 11 eligible women fell from 20.7 during the luteinizing hormone (LH) surge period to 18.7 during the acute postsurge period. No statistically significant differences in the API were observed among samples taken at single time points in the early follicular, midfollicular, midluteal, and late luteal phases. CONCLUSION(S): This study suggests that activation of AMH by proteolytic enzymes is largely stable throughout the ovarian cycle. However, there is a subtle but robust decrease in the level of proAMH relative to AMHN,C in the acute postovulatory period. This may indicate that periovulatory increases in prohormone convertases cause increases in proAMH cleavage rates. Alternatively, rapid changes in the hierarchy of follicle developmental stages during ovulation may result in changes in the relative ratios of proAMH and AMHN,C. PMID- 27362612 TI - Acquisition of Predictable Vertical Visual Targets: Eye-Head Coordination and the Triggering Effect. AB - The study was designed to investigate target acquisition in the vertical plane with emphasis on establishing strategy differences associated with acquisition triggering methods. Eight subjects were tested. Measurements consisted of target acquisition time, eye-head latency differences, velocity of gaze, eyes and head, and head amplitude. Using 3-way repeated measures analyses of variance the results show that the strategy for acquisition of predictable visual targets in vertical plane with the head unrestrained significantly depended on (a) the direction of the gaze motion with respect to the gravity vector (i.e., there is significant up-down asymmetry), (b) the angular distance of the target, and (c) the method of triggering the command to acquire the target-external versus internal. The data also show that when vertical acquisition is compared with triggering methods in the horizontal plane there is a difference in overall strategy for the acquisition of targets with the same spatial distances from straight ahead gaze when both the eyes and head are used. Among the factors contributing to the difference in strategy for vertical target acquisition are the gravitational vector, the relationship of target displacement and vestibular activitation, biomechanical and neural control asymmetries, and the difference in the vertical field of view. PMID- 27362613 TI - Effect of Short Recovery Periods on Ocular Comfort During Daily Lens Wear. AB - PURPOSE: To assess the impact of lens-free intervals of varying lengths on end-of day comfort with soft contact lenses. METHODS: Twenty-five symptomatic lens wearers participated in this randomized, cross-over study involving nine individual 12-hour days: one spectacle (no lens) and eight lens wear days. On each lens wear day, lenses were worn bilaterally in 2-hour intervals, separated by lens-free (recovery) periods of 0, 30, 60, or 80 minutes (repeated throughout the day). For each 2-hour lens wear interval, new lenses were worn. Ocular comfort was rated on a 0 to 100 visual analogue scale (0 = extremely uncomfortable); tear film and ocular parameters were assessed at the beginning and end of each study day. This study involved two different types of silicone hydrogel lenses, and the order of lens type and length of recovery period was randomized. Participants were unaware of the true study purpose and that a new lens pair was used for each lens wear interval. RESULTS: End-of-day comfort on lens wear days was significantly worse than on the spectacle day (p < 0.002). There was no significant effect of the recovery periods on end-of-day comfort (p > 0.05). Although lens wear affected noninvasive tear film break-up time and conjunctival staining, there were no effects of recovery period length on noninvasive tear film break-up time (p > 0.05), tear meniscus height (p > 0.05), corneal staining (p > 0.05), conjunctival staining (p > 0.05), bulbar conjunctival redness (p > 0.05), or limbal redness (p > 0.05). There was no consistent effect of recovery period length on lid margin staining. CONCLUSIONS: Lens-free recovery periods during a 12-hour lens wear day did not positively impact end-of-day comfort in this study. Cumulative lens wear times ranged from 8 to 12 hours, and the results suggest that once the length of lens wear exceeds the usual comfortable wear time, there is no benefit of short recovery periods. PMID- 27362614 TI - What Do Animal Studies Tell Us about the Mechanism of Myopia-Protection by Light? AB - : Human studies have provided strong evidence that exposure to time outdoors is protective against the onset of myopia. A causal factor may be that the light levels outdoors (30,000-130,000 lux) are much higher than light levels indoors (typically less than 500 lux). Studies using animal models have found that normal animals exposed to low illuminance levels (50 lux) can develop myopia. The myopia and axial elongation, produced in animals by monocular form deprivation, is reduced by light levels in the 15,000 to 25,000 range. Myopia induced with a negative-power lens seems less affected, perhaps because the lens provides a powerful target for the emmetropization mechanism. Animal studies suggest that raising the light levels may have their effect by increasing retinal dopamine activity, probably via the D2 receptor pathway, altering gene expression in the retina and reducing the signals that produce axial elongation. PMID- 27362615 TI - Diurnal Variation in Comfort in Contact Lens and Non-contact Lens Wearers. AB - PURPOSE: The purpose of this investigation was to evaluate the diurnal variation in symptoms associated with ocular discomfort in contact lens (CL) wearers and non-CL wearers. METHODS: The study population comprised 604 individuals attending pre-screening visits at the OTG-i research clinic; 60% were current soft CL wearers (hydrogel and silicone hydrogel) and 40% were non-CL wearers. Symptomatology status was determined by the OSDI questionnaire (58% asymptomatic, 42% symptomatic). Participants were asked to grade their comfort, vision, and other symptoms during the day and in the evening (before lens removal for CL wearers) on 0 to 100 visual analogue scales. RESULTS: Diurnal decrease in comfort was significantly greater for CL wearers (-16.0 vs. -6.3, p < 0.001) and symptomatic participants (p = 0.015). Diurnal decrease in subjective vision was also significantly greater for CL wearers (-10.4 vs. -6.9, p = 0.005) and symptomatic participants (p = 0.001), and the interaction between these factors was also significant (p = 0.019). Dryness, grittiness, and irritation increased significantly more for CL wearers (p < 0.001, p = 0.012, and p = 0.004, respectively) and grittiness, irritation, and stinging for symptomatic participants (p = 0.016, p < 0.001, and p < 0.001, respectively). For the CL wearers, there was a significant interaction between dryness and age (p = 0.026) with the diurnal increase in dryness being greater in those under 40 (+15.6 vs. +10.0). CONCLUSIONS: The diurnal decrease in comfort and subjective vision, and the diurnal increase in dryness, grittiness, and irritation, were significantly more marked for CL wearers than non-CL wearers. Diurnal changes in comfort, grittiness, stinging, irritation, and vision were influenced by the subject's overall symptomatology as assessed by the OSDI questionnaire. For dryness symptoms, the diurnal decrease was most marked in young CL wearers. For the symptoms of stinging and vision, the diurnal changes were most pronounced in the symptomatic groups. PMID- 27362616 TI - G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitors: Current Trends and Future Perspectives. AB - G-protein-coupled receptor kinase 2 (GRK2) is a G-protein-coupled receptor kinase that is ubiquitously expressed in many tissues and regulates various intracellular mechanisms. The up- or down-regulation of GRK2 correlates with several pathological disorders. GRK2 plays an important role in the maintenance of heart structure and function; thus, this kinase is involved in many cardiovascular diseases. GRK2 up-regulation can worsen cardiac ischemia; furthermore, increased kinase levels occur during the early stages of heart failure and in hypertensive subjects. GRK2 up-regulation can lead to changes in the insulin signaling cascade, which can translate to insulin resistance. Increased GRK2 levels also correlate with the degree of cognitive impairment that is typically observed in Alzheimer's disease. This article reviews the most potent and selective GRK2 inhibitors that have been developed. We focus on their mechanism of action, inhibition profile, and structure-activity relationships to provide insight into the further development of GRK2 inhibitors as drug candidates. PMID- 27362617 TI - Lipogenesis and lipid peroxidation in rat testes after long-term treatment with sucrose and tannic acid in drinking water. AB - We studied the influence of long-term treatment with sucrose and tannic acid in drinking water on the fatty acid profile and lipid peroxidation in rat testes. Male Wistar rats were supplemented with sucrose (30% w/v) or with sucrose and tannic acid (sucrose 30% w/v, tannic acid 0.1% w/v) in drinking water. The treatment with sucrose elevated blood glucose levels in the plasma (p < .05) and decreased the testis weight (p < .05) and testis index (p < .05) of the rats. Sucrose treatment increased monounsaturated fatty acids (MUFA) and C22:6n3, and decreased n6 fatty acids in testis tissue. Lipid peroxidation was significantly increased after sucrose administration in plasma (p < .05) and testis tissue (p < .01). The addition of tannic acid led to the decrease in lipid peroxidation in the plasma (p < .05) and testis (p < .05), a further increase in MUFA and decrease in n6 fatty acids. In conclusion, sucrose significantly altered the testis fatty acid profile with an increase in MUFA and C22:6n3, and a decrease in n6 fatty acids. Tannic acid attenuated oxidative stress and hyperglycaemia, but it did not improve pathological changes in the fatty acid composition of the testis. PMID- 27362618 TI - Let's Talk: The Conversation Project. PMID- 27362619 TI - Perceived Changes in Sleep in Adults With Epilepsy. AB - BACKGROUND: Epilepsy is the most common chronic neurological disease in the United States, and 70% of diagnoses occur in late adolescence or adulthood. A disease of the brain, epilepsy can affect sleep. Lack of adequate or high-quality sleep can cause decrements in quality of life. Adults living with epilepsy are at especially high risk for sleep alterations, and these changes in sleep can worsen their epilepsy. The purpose of the study was to describe the perceived effect of epilepsy on sleep in adults who developed epilepsy in late adolescence or adulthood. Research questions included (a) "In adults with epilepsy, what is the perceived change in ability to sleep well because of having epilepsy?"; (b) "In adults with epilepsy, is there a significant relationship between perceived changes in ability to sleep well and perceived changes in overall life because of having epilepsy?"; and (c) "In adults with epilepsy, is there a significant relationship between perceived changes in ability to sleep well because of having epilepsy and total Life Changes in Epilepsy Scale (LCES) scores?". METHODS: One hundred seventy-four adults with epilepsy were recruited. Utilizing data collected via the LCES, a quantitative descriptive/correlational design was utilized. Analyses were carried out to answer each research question. RESULTS: The mean score for the sleep item of the LCES was 2.76 (SD = 1.31), indicating an overall negative change in ability to sleep well. There was a statistically significant, strong positive relationship between the sleep and overall life changes items of the LCES (Pearson r = .476, p < .0000) and also between the sleep item and total LCES scores (Pearson r = .620, p < .0000). IMPLICATIONS: Findings from this study contribute to the extant literature by revealing epilepsy-related changes in sleep as perceived by adults living with epilepsy specifically because of having epilepsy. On the basis of findings rendered from this sample, having epilepsy can lead to perceived negative changes in a person's ability to sleep well, and these negative changes are significantly correlated with negative overall life changes. Recommendations for clinical practice and research can be made based on current results. PMID- 27362620 TI - Research Brief: Swedish Translation and Reliability of the Full Outline of Unresponsiveness Score. PMID- 27362622 TI - Medication Adherence in People With Parkinson Disease. PMID- 27362621 TI - Strategies to Alleviate Anxiety Before the Placement of a Stereotactic Radiosurgery Frame. AB - BACKGROUND: Patients scheduled for stereotactic radiosurgery (SRS) need the placement of a head frame for accurate treatment of brain metastases and other abnormalities in the brain. These patients frequently experience anxiety before frame placement. Although there is evidence that preprocedure education can alleviate anxiety, less is known about education for patients undergoing head frame placement. OBJECTIVE: The aim of this study was to determine whether a preprocedure educational intervention can reduce/alleviate anxiety for patients undergoing head frame placement for SRS. METHODS: This study was a practice improvement project using a nonrandomized controlled design to evaluate patients (N = 28) diagnosed with metastasized brain cancer or other abnormalities in the brain. Patients aged >=19 and <75 years were recruited, and all participants had been radiographically diagnosed and were dispositioned for SRS. The control group (n = 14) received the standard preprocedure teaching, and the intervention group (n = 14) received both the standard preprocedure teaching and an additional educational intervention. Data collecting tools included the Hospital Anxiety and Depression Scale and a visual analog scale to measure the patient's anxiety. RESULTS: It was found that, on average, anxiety levels were lower in the intervention group on both the visual analog scale and Hospital Anxiety and Depression Scale. However, the findings did not reach statistical significance, p < .05. CONCLUSION: On the basis of existing literature, preprocedure education has been shown to decrease patient anxiety. This study aimed to determine whether an additional educational intervention impacted anxiety in patients undergoing SRS for metastatic cancer. Although we found that anxiety levels were decreased in the intervention group, this finding did not reach statistical significance. A larger randomized study is needed to confirm the efficacy of such an intervention in this unique patient population. PMID- 27362623 TI - Emotional lability and affective synchrony in borderline personality disorder. AB - Extant research on emotional lability in borderline personality disorder (BPD) has focused almost exclusively on lability of individual emotions or emotion types, with limited research considering how different types of emotions shift together over time. Thus, this study examined the temporal dynamics of emotion in BPD at the level of both individual emotions (i.e., self-conscious emotions [SCE], anger, and anxiety) and mixed emotions (i.e., synchrony between emotions). One hundred forty-four women from the community completed a diagnostic interview and laboratory study involving 5 emotion induction tasks (each of which was preceded and followed by a 5-min resting period or neutral task). State ratings of SCE, anger, and anxiety were provided at 14 time points (before and after each laboratory task and resting period). Hierarchical linear modeling results indicate that women with BPD reported greater mean levels of SCE and Anxiety (but not Anger), and greater lability of Anxiety. Women with BPD also exhibited greater variability in lability of all 3 emotions (suggestive of within-group differences in the relevance of lability to BPD). Results also revealed synchrony (i.e., positive relations) between each possible pair of emotions, regardless of BPD status. Follow-up regression analyses suggest the importance of accounting for lability when examining the role of synchrony in BPD, as the relation of SCE Anger synchrony to BPD symptom severity was moderated by Anger and SCE lability. Specifically, synchronous changes in SCE and Anger were associated with greater BPD symptom severity when large shifts in SCE were paired with minor shifts in Anger. (PsycINFO Database Record PMID- 27362624 TI - Three cases of OXA-48-like carbapenemase producing Enterobacteriaceae (not) detected using Xpert(r) Carba-R. AB - The increasing prevalence of carbapenemase-producing Enterobacteriaceae necessitates laboratories to invest in the detection of these bacteria, both with phenotypic and to a lesser extent molecular methods. OXA-48-like strains are rapidly emerging, especially in Europe. Since the expression level of OXA-48 is low and some strains present with several alleles, some types might be missed by some molecular assays. Three cases of OXA-48-like strains are described here, where the detection was not straightforward. PMID- 27362625 TI - Face-to-Face Packing of 2,3,9,10-Tetrasubstituted Pentacene Derivatives Revealed through a Solid State [4 + 4] Thermal Cycloaddition and Molecular Dynamic Simulation. AB - 2,3,9,10-Substituted pentacene tetraesters and pentacene diester-dinitriles were synthesized. These pentacene derivatives underwent an unusual solid state [4 + 4] thermal dimerization with good efficiency and complete stereoselectivity. This observation indicates this series of pentacene derivatives adopt pi-pi stacking geometry with large mutual overlap in solid state. This notion was confirmed by molecualr dynamic simulation. PMID- 27362626 TI - Effects of induced optical tunable and ferromagnetic behaviors of Ba doped nanocrystalline LaB6. AB - Multiple nanocrystalline rare-earth hexaborides La1-xBaxB6 have been synthesized via a single step solid-state reaction. The Ba doping effects on crystal structure, grain morphology, magnetic and optical absorption properties were investigated using XRD, FESEM, HRTEM, SQUID magnetometry and optical measurements. The results show that all the Ba-doped hexaborides crystallize in the CsCl-type single phase, indicating the Ba atoms occupied the lattice sites of LaB6. The optical absorption results indicate that the absorption valleys of LaB6 are red-shifted from 622 nm to 780 nm when the Ba doping content increases to x = 0.8. The first-principle calculation results reveal that Ba doping reduces the total kinetic energy of the electrons of LaB6, which lead to the absorption valleys moving toward a higher wavelength. Meanwhile, the band gap of BaB6 obtained from optical absorption is in good agreement with the theoretical calculation results. The magnetic measurements results showed that Ba doping lead to room-temperature ferromagnetism of LaB6 due to the different ionic radii of La(3+) and Ba(2+) causing intrinsic crystal defects, which is directly observed experimentally by HRTEM. This is the first time that we have found the tunable optical and ferromagnetic behavior of Ba doped nanocrystalline LaB6. Thus, nanocrystalline La1-xBaxB6, as multi-functional materials, should open up a new route to extend the optical and magnetic applications of LaB6 nanopowder. PMID- 27362627 TI - Effectiveness of Hospital Palliative Care Teams for Cancer Inpatients: A Systematic Review. AB - BACKGROUND: Although the benefits of palliative care in the outpatient setting are well established, there has been little to support the employing of hospital palliative care services for inpatients with cancer. OBJECTIVE: We conducted a systematic literature review to evaluate the effectiveness of palliative care for cancer patients in the acute inpatient hospital setting. METHODS: Two electronic databases-PubMed and CINAHL Plus-were searched for articles published between 1 January 2005 and 28 May 2015. The search was augmented by hand-searches of specific journals and by examining the reference lists of short-listed articles. Studies were included if they evaluated a hospital palliative care service for cancer patients. Data extracted included study design, patient population, study setting, composition of the team, nature of the intervention, outcomes measured, and main findings. RESULTS: No randomized controlled trials were found. There were 14 pre-post studies that evaluated patient outcomes, of which only 2 had a control group. We also reviewed a further seven studies that evaluated other aspects of the palliative care intervention. The studies were not robust enough to confirm the efficacy of hospital palliative care services for cancer patient outcomes. Nonetheless, published studies provide a glimpse into the wider benefits of palliative care interventions. CONCLUSIONS: Data to support the benefit of palliative care interventions in the inpatient acute hospital setting are still lacking. Future studies should employ innovative strategies to further this field of research. PMID- 27362628 TI - Small Artery Elastin Distribution and Architecture-Focus on Three Dimensional Organization. AB - The distribution of ECM proteins within the walls of resistance vessels is complex both in variety of proteins and structural arrangement. In particular, elastin exists as discrete fibers varying in orientation across the adventitia and media as well as often resembling a sheet-like structure in the case of the IEL. Adding to the complexity is the tissue heterogeneity that exists in these structural arrangements. For example, small intracranial cerebral arteries lack adventitial elastin while similar sized arteries from skeletal muscle and intestinal mesentery exhibit a complex adventitial network of elastin fibers. With regard to the IEL, several vascular beds exhibit an elastin sheet with punctate holes/fenestrae while in others the IEL is discontinuous and fibrous in appearance. Importantly, these structural patterns likely sub-serve specific functional properties, including mechanosensing, control of external forces, mechanical properties of the vascular wall, cellular positioning, and communication between cells. Of further significance, these processes are altered in vascular disorders such as hypertension and diabetes mellitus where there is modification of ECM. This brief report focuses on the three-dimensional wall structure of small arteries and considers possible implications with regard to mechanosensing under physiological and pathophysiological conditions. PMID- 27362629 TI - Cyclic (Alkyl)(Amino)Carbene Complexes of Rhodium and Nickel and Their Steric and Electronic Parameters. AB - N-heterocyclic carbenes (NHCs) and cyclic (alkyl)(amino)carbenes (CAACs) are of great interest, as their electronic and steric properties provide a unique class of ligands and organocatalysts. Herein, substitution reactions involving novel carbonyl complexes of rhodium and nickel were studied to provide a deeper understanding of the fundamental electronic factors characterizing CAAC(methyl) , which were compared with the large array of data available for NHC and sterically more demanding CAAC ligands. PMID- 27362630 TI - Induction of stress volatiles and changes in essential oil content and composition upon microwave exposure in the aromatic plant Ocimum basilicum. AB - Exposure to sustained low intensity microwaves can constitute a stress for the plants, but its effects on plant secondary chemistry are poorly known. We studied the influence of GSM and WLAN-frequency microwaves on emissions of volatile organic compounds and content of essential oil in the aromatic plant Ocimum basilicum L. hypothesizing that microwave exposure leads to enhanced emissions of stress volatiles and overall greater investment in secondary compounds. Compared to the control plants, microwave irradiation led to decreased emissions of beta pinene, alpha-phellandrene, bornyl acetate, beta-myrcene, alpha-caryophyllene and benzaldehyde, but increased emissions of eucalyptol, estragole, caryophyllene oxide, and alpha-bergamotene. The highest increase in emission, 21 times greater compared to control, was observed for caryophyllene oxide. The irradiation resulted in increases in the essential oil content, except for the content of phytol which decreased by 41% in the case of GSM-frequency, and 82% in the case of WLAN-frequency microwave irradiation. The strongest increase in response to WLAN irradiation, >17 times greater, was observed for hexadecane and octane contents. Comparisons of volatile compositions by multivariate analyses demonstrated a clear separation of different irradiance treatments, and according to the changes in the volatile emissions, the WLAN-frequency irradiation represented a more severe stress than the GSM-frequency irradiation. Overall, these results demonstrating important modifications in the emission rates, essential oil content and composition indicate that microwave irradiation influences the quality of herbage of this economically important spice plant. PMID- 27362631 TI - Risks and benefits of marginal biomass-derived biochars for plant growth. AB - In this study, 19 biochars from marginal biomass, representing all major biomass groups (woody materials, grass, an aquatic plant, anthropogenic wastes) were investigated regarding their content of available potentially toxic elements (PTEs) and nutrients (determined by NH4NO3-extractions) and their effects on cress (Lepidium sativum) seedling growth. The objective was to assess the potential and actual effects of biochar with increased PTE content on plant growth in the context of use in soil amendments and growing media. It showed that the percentage of available PTEs was highest for biochars produced at the highest treatment temperature (HTT) of 750 degrees C. On average, however, for all 19 biochars, the percentage availability of Cu, Cr, Ni and Zn (<1.5% for all) was similar to the percentage availability reported in the literature for the same elements in soils at similar pH values which is a highly important finding. Most biochars exceeded German soil threshold values for NH4NO3-extractable PTEs, such as Zn (by up to 25-fold), As and Cd. Despite this, cress seedling growth tests with 5% biochar in sand did not show any correlations between inhibitory effects (observed in 5 of the 19 biochars) and the available PTE concentrations. Instead, the available K concentration and biochar pH were highly significantly, negatively correlated with seedling growth (K: p<0.001, pH: p=0.004). K had the highest available concentration of all elements and the highest percentage availability (47.7+/-19.7% of the total K was available). Consequently, available K contributed most to the osmotic pressure and high pH which negatively affected the seedlings. Although a potential risk if some of these marginal biomass derived biochar were applied at high concentrations, e.g. 5% (>100tha(-1)), when applied at agriculturally realistic application rates (1-10tha(-1)), the resulting smaller increases in pH and available K concentration may actually be beneficial for plant growth. PMID- 27362632 TI - Extreme urban-rural temperatures in the coastal city of Turku, Finland: Quantification and visualization based on a generalized additive model. AB - Fundamental knowledge on the determinants of air temperatures across spatial and temporal scales is essential in climate change mitigation and adaptation. Spatial based statistical modelling provides an efficient approach for the analysis and prediction of air temperatures in human-modified environments at high spatial accuracy. The aim of the study was firstly, to analyse the environmental factors affecting extreme air temperature conditions in a coastal high-latitude city and secondly, to explore the applicability of generalized additive model (GAM) in the study of urban-rural temperatures. We utilized air temperature data from 50 permanent temperature logger stations and extensive geospatial environmental data on different scales from Turku, SW Finland. We selected five temperature situations (cases) and altogether 12 urban and natural explanatory variables for the analyses. The results displayed that (i) water bodies and topographical conditions were often more important than urban variables in controlling the spatial variability of extreme air temperatures, (ii) case specificity of the explanatory variables and their scales should be considered in the analyses and (iii) GAM was highly suitable in quantifying and visualizing the relations between urban-rural temperatures and environmental determinants at local scales. The results promote the use of GAMs in spatial-based statistical modelling of air temperature in future. PMID- 27362633 TI - Evaluation of Retinal Function and Morphology of the Pink-Eyed Royal College of Surgeons (RCS) Rat: A Comparative Study of in Vivo and in Vitro Methods. AB - PURPOSE: To characterize the course of retinal degeneration in the pink-eyed RCS rat in vivo and in vitro. METHODS: Retinal function of RCS rats at the age of 2 to 100 weeks was determined in vivo using full-field electroretinography (ERG). Retinal morphology was evaluated in vivo using spectral domain Optical Coherence Tomography (sd-OCT) and Fluorescence angiography (FA) as well as postmortem using immunohistochemistry (IH). As a control, retinal function and morphology of non dystrophic Wistar rats were analyzed. RESULTS: RCS rats showed an extinction of the ERG beginning with the age of 4 weeks. In the OCT, the outer part of the retina (OPR) could be clearly distinguished from the inner part of the retina (IPR) until the age of 8 weeks. However, at this age, it was impossible to determine from OCT images whether the OPR was formed by the outer nuclear layer (ONL) or by cellular debris built in the course of retinal degeneration. In contrast, immunohistochemistry always enabled to differentiate between ONL and debris (RCS 4 weeks of age: OPR mainly formed by ONL; RCS 8 weeks of age: OPR consisted mainly of cell debris, only 1-2 cell rows of photoreceptor somata were left). CONCLUSIONS: In general, data obtained in vivo were confirmed by data obtained post mortem. Apart from the problem to differentiate between debris and ONL at the age of 8 weeks in the RCS rat, ERG and OCT are useful methods to evaluate retinal function and structure in vivo and to complement immunohistochemical analysis of the degeneration process. PMID- 27362634 TI - The power of local action in occupational health: the adoption of local exhaust ventilation in the Chicago tuckpointing trade. AB - BACKGROUND: Silica is a pervasive and potentially deadly occupational hazard in construction. The occupational risk posed by silica has long been known, but efforts to use engineering controls to minimize dust generation in tuckpointing operations, a masonry restoration specialty, have been slow. OBJECTIVES: The objective of this study is to explore how local innovation in occupational safety and health may emerge, absent the establishment of national standards. METHOD: This study uses a case study to explore the adoption of local exhaust ventilation in tuckpointing operations in the Chicago area. Sources of data for this research include interviews with a diverse range of key informants and the review of archival material. RESULTS: This case study found local unions, municipal regulators, contractors, and major public users of construction services played a central role in the events and milestones that led to the early adoption of local exhaust ventilation in Chicago. The adoption of local exhaust ventilation technology in Chicago demonstrates the potential for local actors to fill an important void when rulemaking in vital areas of occupational of health impedes effective national regulation. PMID- 27362635 TI - Flexible Paper Electrodes for Li-Ion Batteries Using Low Amount of TEMPO-Oxidized Cellulose Nanofibrils as Binder. AB - Flexible Li-ion batteries attract increasing interest for applications in bendable and wearable electronic devices. TEMPO-oxidized cellulose nanofibrils (TOCNF), a renewable material, is a promising candidate as binder for flexible Li ion batteries with good mechanical properties. Paper batteries can be produced using a water-based paper making process, avoiding the use of toxic solvents. In this work, finely dispersed TOCNF was used and showed good binding properties at concentrations as low as 4 wt %. The TOCNF was characterized using atomic force microscopy and found to be well dispersed with fibrils of average widths of about 2.7 nm and lengths of approximately 0.1-1 MUm. Traces of moisture, trapped in the hygroscopic cellulose, is a concern when the material is used in Li-ion batteries. The low amount of binder reduces possible moisture and also increases the capacity of the electrodes, based on total weight. Effects of moisture on electrochemical battery performance were studied on electrodes dried at 110 degrees C in a vacuum for varying periods. It was found that increased drying time slightly increased the specific capacities of the LiFePO4 electrodes, whereas the capacities of the graphite electrodes decreased. The Coulombic efficiencies of the electrodes were not much affected by the varying drying times. Drying the electrodes for 1 h was enough to achieve good electrochemical performance. Addition of vinylene carbonate to the electrolyte had a positive effect on cycling for both graphite and LiFePO4. A failure mechanism observed at high TOCNF concentrations is the formation of compact films in the electrodes. PMID- 27362636 TI - Image-driven, model-based 3D abdominal motion estimation for MR-guided radiotherapy. AB - Respiratory motion introduces substantial uncertainties in abdominal radiotherapy for which traditionally large margins are used. The MR-Linac will open up the opportunity to acquire high resolution MR images just prior to radiation and during treatment. However, volumetric MRI time series are not able to characterize 3D tumor and organ-at-risk motion with sufficient temporal resolution. In this study we propose a method to estimate 3D deformation vector fields (DVFs) with high spatial and temporal resolution based on fast 2D imaging and a subject-specific motion model based on respiratory correlated MRI. In a pre beam phase, a retrospectively sorted 4D-MRI is acquired, from which the motion is parameterized using a principal component analysis. This motion model is used in combination with fast 2D cine-MR images, which are acquired during radiation, to generate full field-of-view 3D DVFs with a temporal resolution of 476 ms. The geometrical accuracies of the input data (4D-MRI and 2D multi-slice acquisitions) and the fitting procedure were determined using an MR-compatible motion phantom and found to be 1.0-1.5 mm on average. The framework was tested on seven healthy volunteers for both the pancreas and the kidney. The calculated motion was independently validated using one of the 2D slices, with an average error of 1.45 mm. The calculated 3D DVFs can be used retrospectively for treatment simulations, plan evaluations, or to determine the accumulated dose for both the tumor and organs-at-risk on a subject-specific basis in MR-guided radiotherapy. PMID- 27362637 TI - The Use of Field and Mesocosm Experiments to Quantify Effects of Physical and Chemical Stressors in Mining-Contaminated Streams. AB - Identifying causal relationships between acid mine drainage (AMD) and ecological responses in the field is challenging. In addition to the direct toxicological effects of elevated metals and reduced pH, mining activities influence aquatic organisms indirectly through physical alterations of habitat. The primary goal of this research was to quantify the relative importance of physical (metal-oxide deposition) and chemical (elevated metal concentrations) stressors on benthic macroinvertebrate communities. Mesocosm experiments conducted with natural assemblages of benthic macroinvertebrates established concentration-response relationships between metals and community structure. Field experiments quantified effects of metal-oxide contaminated substrate and showed significant differences in sensitivity among taxa. To predict the recovery of dominant taxa in the field, we integrated our measures of metal tolerance and substrate tolerance with estimates of drift propensity obtained from the literature. Our estimates of recovery were consistent with patterns observed at downstream recovery sites in the NFCC, which were dominated by caddisflies and baetid mayflies. We conclude that mesocosm and small-scale field experiments, particularly those conducted with natural communities, provide an ecologically realistic complement to laboratory toxicity tests. These experiments also control for the confounding variables associated with field-based approaches, thereby supporting causal relationships between AMD stressors and responses. PMID- 27362639 TI - Investigating Biological Control Agents for Controlling Invasive Populations of the Mealybug Pseudococcus comstocki in France. AB - Pseudococcus comstocki (Hemiptera: Pseudococcidae) is a mealybug species native to Eastern Asia and present as an invasive pest in northern Italy and southern France since the start of the century. It infests apple and pear trees, grapevines and some ornamental trees. Biocontrol programmes against this pest proved successful in central Asia and North America in the second half of the 20th century. In this study, we investigated possible biocontrol agents against P. comstocki, with the aim of developing a biocontrol programme in France. We carried out systematic DNA-barcoding at each step in the search for a specialist parasitoid. First we characterised the French target populations of P. comstocki. We then identified the parasitoids attacking P. comstocki in France. Finally, we searched for foreign mealybug populations identified a priori as P. comstocki and surveyed their hymenopteran parasitoids. Three mealybug species (P. comstocki, P. viburni and P. cryptus) were identified during the survey, together with at least 16 different parasitoid taxa. We selected candidate biological control agent populations for use against P. comstocki in France, from the species Allotropa burrelli (Hymenoptera: Platygastridae) and Acerophagus malinus (Hymenoptera: Encyrtidae). The coupling of molecular and morphological characterisation for both pests and natural enemies facilitated the programme development and the rejection of unsuitable or generalist parasitoids. PMID- 27362638 TI - Detection of Post-Therapeutic Effects in Breast Carcinoma Using Hard X-Ray Index of Refraction Computed Tomography - A Feasibility Study. AB - OBJECTIVES: Neoadjuvant chemotherapy is the state-of-the-art treatment in advanced breast cancer. A correct visualization of the post-therapeutic tumor size is of high prognostic relevance. X-ray phase-contrast computed tomography (PC-CT) has been shown to provide improved soft-tissue contrast at a resolution formerly restricted to histopathology, at low doses. This study aimed at assessing ex-vivo the potential use of PC-CT for visualizing the effects of neoadjuvant chemotherapy on breast carcinoma. MATERIALS AND METHODS: The analysis was performed on two ex-vivo formalin-fixed mastectomy samples containing an invasive carcinoma removed from two patients treated with neoadjuvant chemotherapy. Images were matched with corresponding histological slices. The visibility of typical post-therapeutic tissue changes was assessed and compared to results obtained with conventional clinical imaging modalities. RESULTS: PC-CT depicted the different tissue types with an excellent correlation to histopathology. Post-therapeutic tissue changes were correctly visualized and the residual tumor mass could be detected. PC-CT outperformed clinical imaging modalities in the detection of chemotherapy-induced tissue alterations including post-therapeutic tumor size. CONCLUSIONS: PC-CT might become a unique diagnostic tool in the prediction of tumor response to neoadjuvant chemotherapy. PC-CT might be used to assist during histopathological diagnosis, offering a high-resolution and high-contrast virtual histological tool for the accurate delineation of tumor boundaries. PMID- 27362640 TI - Southern Europe's Coming Plagues: Vector-Borne Neglected Tropical Diseases. PMID- 27362641 TI - Nosocomial influenza: encouraging insights and future challenges. AB - PURPOSE OF REVIEW: The prevalence and incidence of viral nosocomial influenza infections in healthcare settings are underestimated. Nosocomial influenza outbreaks are frequent, and control remains challenging in acute care and long term healthcare settings. This review examines recent publications on the determinants of nosocomial influenza prevention and control. RECENT FINDINGS: Nosocomial influenza outbreaks occur in various healthcare settings, especially among the frail and elderly. The correct diagnosis is commonly missed because a substantial proportion of asymptomatic cases can transmit infections. Rapid diagnosis will facilitate rapid identification of cases and the implementation of control measures but needs confirmation in some circumstances, such as the description of transmission chains. Links between patients and healthcare personnel (HCP) have been well explored by phylogenetic virus characterization and need additional refinement and study. The preventive role of HCP vaccination in influenza incidence among patients should be investigated further in various settings to take into account different strategies for vaccination (i.e. voluntary or mandatory vaccination policies). Indeed, in Europe, influenza vaccination remains modest, whereas in North America hospitals and some states and provinces are now mandating influenza vaccination among HCP. The variability of vaccine effectiveness by seasonal epidemics is also an important consideration for control strategies. SUMMARY: When influenza cases occur in the community, the risk of transmission and nosocomial cases increase in healthcare settings requiring vigilance among staff. Surveillance and early warning systems should be encouraged. Outbreak control needs appropriate identification of cases and transmission chains, and rapid implementation of control measures. Vaccination policies in conjunction with appropriate infection control measures could reduce virus spreading in hospitals. HCP vaccination coverage must be improved. PMID- 27362642 TI - Breathless and young-In need of inspiration? PMID- 27362643 TI - Acoustic Structure and Contextual Use of Calls by Captive Male and Female Cheetahs (Acinonyx jubatus). AB - The vocal repertoire of captive cheetahs (Acinonyx jubatus) and the specific role of meow vocalizations in communication of this species attract research interest about two dozen years. Here, we expand this research focus for the contextual use of call types, sex differences and individual differences at short and long terms. During 457 trials of acoustic recordings, we collected calls (n = 8120) and data on their contextual use for 13 adult cheetahs (6 males and 7 females) in four Russian zoos. The cheetah vocal repertoire comprised 7 call types produced in 8 behavioural contexts. Context-specific call types (chirr, growl, howl and hiss) were related to courting behaviour (chirr) or to aggressive behaviour (growl, howl and hiss). Other call types (chirp, purr and meow) were not context specific. The values of acoustic variables differed between call types. The meow was the most often call type. Discriminant function analysis revealed a high potential of meows to encode individual identity and sex at short terms, however, the vocal individuality was unstable over years. We discuss the contextual use and acoustic variables of call types, the ratios of individual and sex differences in calls and the pathways of vocal ontogeny in the cheetah with relevant data on vocalization of other animals. PMID- 27362644 TI - The Cytoophidium and Its Kind: Filamentation and Compartmentation of Metabolic Enzymes. AB - Compartmentation is essential for the localization of biological processes within a cell. In 2010, three groups independently reported that cytidine triphosphate synthase (CTPS), a metabolic enzyme for de novo synthesis of the nucleotide CTP, is compartmentalized in cytoophidia (Greek for "cellular snakes") in bacteria, yeast, and fruit flies. Subsequent studies demonstrate that CTPS can also form filaments in human cells. Thus, the cytoophidium represents a new type of intracellular compartment that is strikingly conserved across prokaryotes and eukaryotes. Multiple lines of evidence have recently suggested that polymerization of metabolic enzymes such as CTPS and inosine monophosphate dehydrogenase into filamentous cytoophidia modulates enzymatic activity. With many more metabolic enzymes found to form the cytoophidium and its kind, compartmentation via filamentation may serve as a general mechanism for the regulation of metabolism. PMID- 27362645 TI - Cytoplasmic Streaming in the Drosophila Oocyte. AB - Objects are commonly moved within the cell by either passive diffusion or active directed transport. A third possibility is advection, in which objects within the cytoplasm are moved with the flow of the cytoplasm. Bulk movement of the cytoplasm, or streaming, as required for advection, is more common in large cells than in small cells. For example, streaming is observed in elongated plant cells and the oocytes of several species. In the Drosophila oocyte, two stages of streaming are observed: relatively slow streaming during mid-oogenesis and streaming that is approximately ten times faster during late oogenesis. These flows are implicated in two processes: polarity establishment and mixing. In this review, I discuss the underlying mechanism of streaming, how slow and fast streaming are differentiated, and what we know about the physiological roles of the two types of streaming. PMID- 27362646 TI - Emergence and Evolution of Secondary Lymphoid Organs. AB - For effective adaptive immunity to foreign antigens (Ag), secondary lymphoid organs (SLO) provide the confined environment in which Ag-restricted lymphocytes, with very low precursor frequencies, interact with Ag on Ag-presenting cells (APC). The spleen is the primordial SLO, arising in conjunction with adaptive immunity in early jawed vertebrates. The spleen, especially the spleen's lymphoid compartment, the white pulp (WP), has undergone numerous modifications over evolutionary time. We describe the progressive advancement of splenic WP complexity, which evolved in parallel with the increasing functionality of adaptive immunity. The Ag-presenting function of follicular dendritic cells (FDC) also likely emerged at the inception of adaptive immunity, and we propose that a single type of hematopoietically derived APC displayed Ag to both T and B cells. A dedicated FDC, derived from a vascular precursor, is a recent evolutionary innovation that likely permitted the robust affinity maturation found in mammals. PMID- 27362647 TI - Survival Analysis with Multiple Causes of Death: Extending the Competing Risks Model. AB - Statistics on mortality related to each disease are usually based on the so called underlying cause of death, which is selected from the diseases declared on the standardized death certificate using international rules. However, the assumption that each death is caused by exactly one disease is debatable, particularly with an aging population in an era where infectious diseases are replaced by chronic and degenerative diseases. The need to consider multiple causes of death has been acknowledged in epidemiologic research, with a growing body of literature producing statistics based on any mention of a disease on the death certificate. Yet there has not been a formal framework proposed for the statistical modeling of death arising from multiple causes. We propose a model for multiple cause of death data grounded on an empirical approach that assigns weights to each cause on the death certificate. We describe how this model for multiple-cause mortality, which extends the usual competing risks model used to conceptualize single-cause mortality, can serve to study the burden and etiology of mortality related to each disease, particularly using Cox regression methodology. We discuss how the multiple-cause, single-cause, and "any-mention" approaches compare in this regard. A simulation study and an application to a study of socioeconomic inequalities in mortality show the value of the proposed methods for exploiting this precious source of data to gain new insights, especially for certain diseases. See video abstract at, http://links.lww.com/EDE/B84. PMID- 27362649 TI - Fixation of Co2 by Zinc(II) Chelates in Alcoholic Medium. X-ray Structures of {[Zn(cyclen)]3(MU3-Co3)}(ClO4)4 and [Zn(cyclen)EtOH](ClO4]2. PMID- 27362648 TI - Association Study Between SLC15A4 Polymorphisms and Haplotypes and Systemic Lupus Erythematosus in a Han Chinese Population. AB - OBJECTIVE: The gene SLC15A4 (solute carrier family 15 [oligopeptide transporter], member 4) has been reported as contributing to the pathogenesis of systemic lupus erythematosus (SLE). We performed a case-control replication study to investigate further the association between single-nucleotide polymorphisms (SNPs) in the SLC15A4 gene and systemic SLE in a Han Chinese population. METHODS: In Han Chinese SLE patients and healthy individuals (n = 355, 375, respectively), 18 SNPs in the SLC15A4 gene were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and TaqMan SNP genotyping assays. Analyses of allele frequencies and genotypes using codominant, dominant, and recessive models were conducted, as well as a linkage disequilibrium analysis. P values < 0.05 were considered significant. RESULTS: Allele frequencies of five of the analyzed SNPs were significantly associated with SLE. Under a codominant model the genotype frequencies of rs3765108 AG and rs7308691 AT were significantly higher in the SLE group than the control group (p = 0.019, 0.049, respectively). Under a dominant model the rs1385374 (TT+CT) SNP carried a higher risk of SLE than (CC) (p = 0.042). One SLC15A4 haplotype (TA), which consists of 2 SNPs (rs959989 and rs983492), was associated with SLE (p = 0.024). CONCLUSION: Our study determined that five SNPs (rs959989, rs1385374, rs983492, rs12298615, and rs10847697) are associated with SLE. Thus, SLC15A4 may be important in the pathogenesis of SLE in Han Chinese patients. PMID- 27362650 TI - Rickettsia australis Activates Inflammasome in Human and Murine Macrophages. AB - Rickettsiae actively escape from vacuoles and replicate free in the cytoplasm of host cells, where inflammasomes survey the invading pathogens. In the present study, we investigated the interactions of Rickettsia australis with the inflammasome in both mouse and human macrophages. R. australis induced a significant level of IL-1beta secretion by human macrophages, which was significantly reduced upon treatment with an inhibitor of caspase-1 compared to untreated controls, suggesting caspase-1-dependent inflammasome activation. Rickettsia induced significant secretion of IL-1beta and IL-18 in vitro by infected mouse bone marrow-derived macrophages (BMMs) as early as 8-12 h post infection (p.i.) in a dose-dependent manner. Secretion of these cytokines was accompanied by cleavage of caspase-1 and was completely abrogated in BMMs deficient in caspase-1/caspase-11 or apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), suggesting that R. australis activate the ASC-dependent inflammasome. Interestingly, in response to the same quantity of rickettsiae, NLRP3-/- BMMs significantly reduced the secretion level of IL-1beta compared to wild type (WT) controls, suggesting that NLRP3 inflammasome contributes to cytosolic recognition of R. australis in vitro. Rickettsial load in spleen, but not liver and lung, of R. australis-infected NLRP3-/- mice was significantly greater compared to WT mice. These data suggest that NLRP3 inflammasome plays a role in host control of bacteria in vivo in a tissue-specific manner. Taken together, our data, for the first time, illustrate the activation of ASC-dependent inflammasome by R. australis in macrophages in which NLRP3 is involved. PMID- 27362651 TI - Regulating mechanical tension at compartment boundaries in Drosophila. AB - During animal development, cells with similar function and fate often stay together and sort out from cells with different fates. In Drosophila wing imaginal discs, cells of anterior and posterior fates are separated by a straight compartment boundary. Separation of anterior and posterior cells requires the homeodomain-containing protein Engrailed, which is expressed in posterior cells. Engrailed induces the expression of the short-range signaling molecule Hedgehog in posterior cells and confines Hedgehog signal transduction to anterior cells. Transduction of the Hedgehog signal in anterior cells is required for the separation of anterior and posterior cells. Previous work showed that this separation of cells involves a local increase in mechanical tension at cell junctions along the compartment boundary. However, how mechanical tension was locally increased along the compartment boundary remained unknown. A recent paper now shows that the difference in Hedgehog signal transduction between anterior and posterior cells is necessary and sufficient to increase mechanical tension. The local increase in mechanical tension biases junctional rearrangements during cell intercalations to maintain the straight shape of the compartment boundary. These data highlight how developmental signals can generate patterns of mechanical tension important for tissue organization. PMID- 27362652 TI - miR-34 miRNAs Regulate Cellular Senescence in Type II Alveolar Epithelial Cells of Patients with Idiopathic Pulmonary Fibrosis. AB - Pathologic features of idiopathic pulmonary fibrosis (IPF) include genetic predisposition, activation of the unfolded protein response, telomere attrition, and cellular senescence. The mechanisms leading to alveolar epithelial cell (AEC) senescence are poorly understood. MicroRNAs (miRNAs) have been reported as regulators of cellular senescence. Senescence markers including p16, p21, p53, and senescence-associated beta-galactosidase (SA-betagal) activity were measured in type II AECs from IPF lungs and unused donor lungs. miRNAs were quantified in type II AECs using gene expression arrays and quantitative RT-PCR. Molecular markers of senescence (p16, p21, and p53) were elevated in IPF type II AECs. SA betagal activity was detected in a greater percentage in type II AECs isolated from IPF patients (23.1%) compared to patients with other interstitial lung diseases (1.2%) or normal controls (0.8%). The relative levels of senescence associated miRNAs miR-34a, miR-34b, and miR-34c, but not miR-20a, miR-29c, or miR let-7f were significantly higher in type II AECs from IPF patients. Overexpression of miR-34a, miR-34b, or miR-34c in lung epithelial cells was associated with higher SA-betagal activity (27.8%, 35.1%, and 38.2%, respectively) relative to control treated cells (8.8%). Targets of miR-34 miRNAs, including E2F1, c-Myc, and cyclin E2, were lower in IPF type II AECs. These results show that markers of senescence are uniquely elevated in IPF type II AECs and suggest that the miR-34 family of miRNAs regulate senescence in IPF type II AECs. PMID- 27362653 TI - Cangrelor for the management and prevention of arterial thrombosis. AB - INTRODUCTION: Despite advances in antiplatelet therapy, the optimum antithrombotic regimen during percutaneous coronary intervention (PCI) remains to be determined. Cangrelor is an intravenous, reversibly-binding platelet P2Y12 receptor antagonist with ultra-rapid onset and offset of action that is approved in Europe and United States for use in patients undergoing PCI. This article describes the background for the development of cangrelor, the biology, pharmacology and clinical evidence supporting its use, and its likely position in the future. AREAS COVERED: The role of the platelet P2Y12 receptor in platelet biology and the implications of this for atherothrombotic disease are described. Currently unmet needs in antithrombotic management during and after PCI are discussed followed by a description of the chemistry, pharmacokinetics and pharmacodynamics of cangrelor, including its interactions with oral thienopyridines. Subsequently, the clinical trial evidence supporting its adoption into clinical practice is reviewed, including the evidence indicating its superiority over a strategy based on clopidogrel treatment alone. Expert commentary: The current status and future potential of cangrelor is discussed, including a view of its place in current clinical practice. PMID- 27362654 TI - Iterative Bayesian Estimation of Travel Times on Urban Arterials: Fusing Loop Detector and Probe Vehicle Data. AB - On urban arterials, travel time estimation is challenging especially from various data sources. Typically, fusing loop detector data and probe vehicle data to estimate travel time is a troublesome issue while considering the data issue of uncertain, imprecise and even conflicting. In this paper, we propose an improved data fusing methodology for link travel time estimation. Link travel times are simultaneously pre-estimated using loop detector data and probe vehicle data, based on which Bayesian fusion is then applied to fuse the estimated travel times. Next, Iterative Bayesian estimation is proposed to improve Bayesian fusion by incorporating two strategies: 1) substitution strategy which replaces the lower accurate travel time estimation from one sensor with the current fused travel time; and 2) specially-designed conditions for convergence which restrict the estimated travel time in a reasonable range. The estimation results show that, the proposed method outperforms probe vehicle data based method, loop detector based method and single Bayesian fusion, and the mean absolute percentage error is reduced to 4.8%. Additionally, iterative Bayesian estimation performs better for lighter traffic flows when the variability of travel time is practically higher than other periods. PMID- 27362655 TI - Neonatal Whisker Trimming Impairs Fear/Anxiety-Related Emotional Systems of the Amygdala and Social Behaviors in Adult Mice. AB - Abnormalities in tactile perception, such as sensory defensiveness, are common features in autism spectrum disorder (ASD). While not a diagnostic criterion for ASD, deficits in tactile perception contribute to the observed lack of social communication skills. However, the influence of tactile perception deficits on the development of social behaviors remains uncertain, as do the effects on neuronal circuits related to the emotional regulation of social interactions. In neonatal rodents, whiskers are the most important tactile apparatus, so bilateral whisker trimming is used as a model of early tactile deprivation. To address the influence of tactile deprivation on adult behavior, we performed bilateral whisker trimming in mice for 10 days after birth (BWT10 mice) and examined social behaviors, tactile discrimination, and c-Fos expression, a marker of neural activation, in adults after full whisker regrowth. Adult BWT10 mice exhibited significantly shorter crossable distances in the gap-crossing test than age matched controls, indicating persistent deficits in whisker-dependent tactile perception. In contrast to controls, BWT10 mice exhibited no preference for the social compartment containing a conspecific in the three-chamber test. Furthermore, the development of amygdala circuitry was severely affected in BWT10 mice. Based on the c-Fos expression pattern, hyperactivity was found in BWT10 amygdala circuits for processing fear/anxiety-related responses to height stress but not in circuits for processing reward stimuli during whisker-dependent cued learning. These results demonstrate that neonatal whisker trimming and concomitant whisker-dependent tactile discrimination impairment severely disturbs the development of amygdala-dependent emotional regulation. PMID- 27362656 TI - Characteristics of Protons Exiting from a Polyethylene Converter Irradiated by Neutrons with Energies between 1 keV and 10 MeV. AB - Monte Carlo method has been used to determine the efficiency for proton production and to study the energy and angular distributions of the generated protons. The ENDF library of cross sections is used to simulate the interactions between the neutrons and the atoms in a polyethylene (PE) layer, while the ranges of protons with different energies in PE are determined using the Stopping and Range of Ions in Matter (SRIM) computer code. The efficiency of proton production increases with the PE layer thickness. However the proton escaping from a certain polyethylene volume is highly dependent on the neutron energy and target thickness, except for a very thin PE layer. The energy and angular distributions of protons are also estimated in the present paper, showing that, for the range of energy and thickness considered, the proton flux escaping is dependent on the PE layer thickness, with the presence of an optimal thickness for a fixed primary neutron energy. PMID- 27362657 TI - Are Sport-Specific Profiles of Tendon Stiffness and Cross-Sectional Area Determined by Structural or Functional Integrity? AB - The present study aimed to determine whether distinct sets of tendon properties are seen in athletes engaged in sports with contrasting requirements for tendon function and structural integrity. Patellar and Achilles tendon morphology and force-deformation relation were measured by combining ultrasonography, electromyography and dynamometry in elite ski jumpers, distance runners, water polo players and sedentary individuals. Tendon cross-sectional area normalized to body mass2/3 was smaller in water polo players than in other athletes (patellar and Achilles tendon; -28 to -24%) or controls (patellar tendon only; -9%). In contrast, the normalized cross-sectional area was larger in runners (patellar tendon only; +26%) and ski jumpers (patellar and Achilles tendon; +21% and +13%, respectively) than in controls. Tendon stiffness normalized to body mass2/3 only differed in ski jumpers, compared to controls (patellar and Achilles tendon; +11% and +27%, respectively) and to water polo players (Achilles tendon only; +23%). Tendon size appears as an adjusting variable to changes in loading volume and/or intensity, possibly to preserve ultimate strength or fatigue resistance. However, uncoupled morphological and mechanical properties indicate that functional requirements may also influence tendon adaptations. PMID- 27362658 TI - Prevalance, Morphology, and Molecular Characterization of Sarcocystis heydorni Sarcocysts from Cattle (Bos Taurus) in China. AB - Cattle are intermediate hosts for 2 zoonotic species of Sarcocystis, Sarcocystis hominis and Sarcocystis heydorni. Here we report S. heydorni from cattle for the first time in China. Sarcocysts of S. heydorni were found in muscle from 173 of 1,630 (10.6%) cattle in abattoirs (9.7% in skeletal muscles, 3.4% esophagus, 2.5% diaphragm, and 0.1% tongue; heart muscle was negative). By means of light microscopy, S. heydorni sarcocysts were thin-walled (<1 MUm). Using transmission electron microscopy, the sarcocyst wall had short (0.3-0.5 * 0.5-0.9 MUm) stubby protrusions, the tips of which contained electron-dense, disk-shaped plaques, similar to the sarcocyst wall type 29b. In preliminary transmission attempts, a human volunteer did not excrete sporocysts in feces after ingesting 579 sarcocysts S. heydorni isolated from cattle. Phylogenetic analysis using the 2 molecular markers (18S rRNA gene and mitochondrial cox1 gene) indicated S. heydorni shared the closest affinity with species of Sarcocystis, which employ ruminants as intermediate hosts and canids as definitive hosts. PMID- 27362659 TI - Prognostic Impact of Pretreatment Plasma Fibrinogen in Patients with Locally Advanced Oral and Oropharyngeal Cancer. AB - BACKGROUND: We aimed to determine the prognostic significance of pretreatment plasma fibrinigen in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). METHODS: A cohort of 183 patients with locally advanced OOSCC receiving preoperative chemoradiotherapy was retrospectively examined. Using ROC curve analysis, a pretreatment plasma fibrinogen cutoff value of 447mg/dL was determined. The primary endpoints were overall survival and recurrence-free survival. A secondary endpoint was to determine whether pretreatment plasma fibrinogen could predict treatment response to neoadjuvant chemoradiotherapy. Cox regression models and Kaplan-Meier curves were used for survival analyses. RESULTS: Seventy-one patients had an elevated pretreatment plasma fibrinogen (fibrinogen >447mg/dL). Patients with high fibrinogen showed significantly higher pathologic stages after neoadjuvant treatment than those with low fibrinogen (p = 0.037). In univariate analysis, elevated fibrinogen was associated with poor overall survival (p = 0.005) and recurrence-free survival (p = 0.008) Multivariate analysis revealed that elevated fibrinogen remained an independent risk factor for death (hazard ratio 1.78, 95% CI 1.09-2.90, p = 0.021) and relapse (hazard ratio 1.78, 95% CI 1.11-2.86, p = 0.016). CONCLUSION: Elevated pretreatment plasma fibrinogen is associated with lack of response to neoadjuvant chemoradiotherapy and reduced OS and RFS in patients with OOSCC. Thus, plasma fibrinogen may emerge as a novel prognostic indicator and a potential therapeutic target in OOSCC. PMID- 27362660 TI - Secretory aspartyl proteinases induce neutrophil chemotaxis in vivo. PMID- 27362661 TI - New Class of Hydrido Iron(II) Compounds with cis-Reactive Sites: Combination of Iron and Diphosphinodithio Ligand. AB - The cationic complex [Fe(P2 S2 )(NCMe)2 ](2+) (P2 S2 =(Ph2 PC6 H4 CH2 S)2 (C2 H4 ) ([1(NCMe)2 ](2+) )), with two MeCN ligands in a cis orientation, was synthesized and characterized. The MeCN ligand in [1(NCMe)2 ](2+) undergoes further substitution by a hydride ligand or CO to give iron(II) hydrides [H1(NCMe)](+) , [H1H](0) , and [H1(CO)](+) . The order of reactivity of the hydrides was [H1H](0) >[H1(NCMe)](+) >[H1(CO)](+) , and was illustrated by their reactions toward protic acids, the organic cation of 10-methylacridinium (MeAcr(+) ) as a hydride acceptor, and intermolecular hydride transfer reactions among these ferrous compounds. For example, MeAcr(+) was reduced initially by a one-electron transfer process from [H1H](0) , resulting in competing reactions of MeAcr(.) dimerization, hydrogen atom transfer from [H1H](+) to MeAcr(.) , and decomposition of [H1H](+) . MeAcrH was produced in excellent yields through a single-step H(-) transfer from [H1(NCMe)](+) to MeAcr(+) , but [H1(CO)](+) was inactive toward MeAcr(+) . PMID- 27362662 TI - The prevalence of allergic rhinitis and atopic markers in obstructive sleep apnea. AB - Allergic rhinitis (AR) related inflammation might worsen the severity of obstructive sleep apnea (OSA), however, the relationship between the two disorders remains controversial. Our aim was to determine the prevalence of AR and atopic markers in OSA. This cross-sectional study recruited participants with sleep-related complaints referred to a sleep center from February 2013 to June 2014. The diagnosis of OSA was based on the Berlin questionnaire (BQ) followed by confirmatory polysomnography (PSG). The diagnosis of AR was made via focused history and clinical examination and was confirmed by measuring atopic markers. OSA was diagnosed in 97 out of 157 adults attending the sleep clinic (61.8%). There was a high prevalence of AR (52.6%) among OSA individuals. This was not significantly different from the frequency in the non-OSA individuals (p=0.5). Elevated total immunoglobulin E (IgE; >100K/MUL), eosinophil count, and positive Phadiatop tests were found in individuals with OSA to be 37.1%, 11.3%, and 41.2%, respectively. Individuals without OSA have shown similar percentages. In our cohort, there was no significant difference in frequency of AR and atopy among participants with OSA compared to those without OSA. PMID- 27362663 TI - Toxic effects and depuration after the dietary lead(II) exposure on the bioaccumulation and hematological parameters in starry flounder (Platichthys stellatus). AB - Platichthys stellatus (mean length 20+/-2cm, mean weight 160.15+/-15g) were exposed to the different levels of dietary lead(II) at the concentrations of 0, 30, 60, 120, 240mg/kg for 4 weeks. Depuration was conducted for 2 weeks after exposure. The lead exposure over 60mg Pb/kg induced the significant bioaccumulation in tissues of P. stellatus (5-30MUg/g tissue), except for brain and muscle where the exposure to 240mg Pb/kg caused the bioaccumulation (2-4MUg/g tissue). The hematological parameters such as red blood cell (RBC) counts, hematocrit (Ht) value and hemoglobin (Hb) concentration were substantially decreased over 60mg Pb/kg, and lasted even after the depuration period. For plasma components, calcium and magnesium levels in plasma were generally decreased over 60mg Pb/kg, and glucose level was also mainly increased over 60mg Pb/kg. Total protein was significantly decreased over 120mg Pb/kg after 4 weeks exposure. Glucose and total protein showed the restoration after the depuration period in groups of fish exposed previously to over 60 and 120mg Pb/kg, respectively. However, other parameters that changed during the exposure over 60mg Pb/kg did not recovered. For enzymatic components in plasma, glutamic oxalate transminase (GOT), glutamic pyruvate transminase (GPT) and alkaline phosphatase (ALP) were significantly increased over 120mg Pb/kg, and there was only restoration observed after the depuration for ALP over 120mg Pb/kg. PMID- 27362664 TI - Ligustrazine improves blood circulation by suppressing Platelet activation in a rat model of allergic asthma. AB - Chuan-xiong (Ligusticum wallichii) is a traditional herbal medicine in Eastern Asia, but the effect of its active component ligustrazine remains unclear. We explored its effect and possible mechanism in a well-characterized rat model of allergic asthma. Ligustrazine suppressed bronchial hyper-responsiveness to methacholine, and suppressed lung inflammation in asthmatic rats. Ligustrazine exhibited potent immuno-modulatory and anti-inflammatory effects: it suppressed lymphocyte and eosinophil mobilization, and reduced cytokine IL-5 and IL-13 production significantly in lung tissues from asthmatic rats (P<0.05). Further histological examinations clearly demonstrated that ligustrazine improved blood circulation and ameliorated platelet activation, aggregation and adhesion, which induced sustained infiltration and activation of various inflammatory cells, including lymphocytes and eosinophils, followed by synthesis and release of a variety of pro-inflammatory mediators and cytokines. The present study suggests that ligustrazine is a potent agent for the treatment of allergic asthma due to its strong anti-inflammatory and immuno-modulatory properties. PMID- 27362665 TI - Full-endoscopic interlaminar operations in lumbar compressive lesions surgery: prospective study of 350 patients. "Endos" study. AB - BACKGROUND: Full-endoscopic operations of lumbar spine are truly minimally invasive surgical procedures. Endoscopic techniques have become the standard in many areas because of the advantages they offer intraoperatively and after surgery. With the interlaminar and transforaminal approach, two full-endoscopic procedures are available for lumbar compressive lesion operations. Our aim was to present and explain all aspects of the full-endoscopic operative technique, and presentation of results of lumbar discectomies and monosegmental decompression in full-endoscopic interlaminar technique performed during 3 year period in comparison with conventional microsurgical operations reported in literature. METHOD: A series of 350 patients underwent full-endoscopic interlaminar lumbar discectomy, and spinal canal decompression, during a 3-year period, is analyzed. In addition to general and specific parameters, VAS and ODI scale are used as measuring instruments. RESULTS: In our clinical series of full-endoscopic operations 88% of the patients no longer had leg pain postoperatively, and 7% had only occasional pain. In seven (2%) patients minor nerve damage resulted in transient paresthesias, and in two patients resulted in neurological deficit. Dural tear occurred in 8 (2.3%) patients, and only one had reoperation for direct dural repair. The recurrence rate was 5,7% (3.7% had reoperation). Resection of the herniated disc and sufficient decompression was technically possible in all cases. CONCLUSION: The clinical results of the full-endoscopic technique are at least equal to those of the conventional microsurgical discectomy with advantages such as reduced tissue trauma, improved patient mobility, and lower overall complication rate. With the possibility of selecting the most adequate approach, lumbar disc herniations inside and outside the spinal canal, can be sufficiently removed using the full-endoscopic technique, when taking the appropriate indication criteria into account. PMID- 27362666 TI - Is hockey just a game? Contesting meanings of the ice hockey life projects through a career-threatening injury. AB - This study is situated within an existential-narrative theoretical framework to examine the impact of career-threatening injury on professional ice hockey players' well-being and career construction. Professional ice hockey culture is construed as a privileged space characterised by hegemonic masculinity, fierce competition as well as high-risk behaviours often resulting in sports injuries. In this paper, we analyse two players' life stories with a particular focus on injury as a boundary situation involving social and temporal breakdown and re evaluation of meaning of sporting life projects. Emergent narratives surrounding existential themes of loss of meaning and loneliness in the face of injury were analysed in connection with players' search for authenticity and realignment with self-concept. Each player developed resistant narratives to the dominant ethos of professional sport in order to restore well-being and sense of self. The relational aspects of injury are highlighted in practical recommendations. PMID- 27362667 TI - Development of a Library Search-Based Screening System for 3,4 Methylenedioxymethamphetamine in Ecstasy Tablets Using a Portable Near-Infrared Spectrometer. AB - This is the first report on development of a library search-based screening system for 3,4-methylenedioxymethamphetamine (MDMA) in ecstasy tablets using a portable near-infrared (NIR) spectrometer. The spectrum library consisted of spectra originating from standard substances as well as mixtures of MDMA hydrochloride (MDMA-HCl) and diluents. The raw NIR spectra were mathematically pretreated, and then, a library search was performed using correlation coefficient. To enhance the discrimination ability, the wavelength used for the library search was limited. Mixtures of MDMA-HCl and diluents were used to decide criteria to judge MDMA-positive or MDMA-negative. Confiscated MDMA tablets and medicinal tablets were used for performance check of the criteria. Twenty-two of 27 MDMA tablets were truly judged as MDMA-positive. Five false-negative results may be caused by compounds not included in the library. No false-positive results were obtained for medicinal tablets. This system will be a useful tool for on site screening of MDMA tablets. PMID- 27362668 TI - Cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion for the treatment of gastric cancer: A single-centre retrospective study. AB - AIM: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemoperfusion (HIPEC) is the treatment regime most likely to achieve prolonged survival in patients with peritoneal carcinomatosis from gastroenteric cancer. To date, few publications have focused on the treatment of patients with gastric cancer alone. Several controversies remain unsolved, including the safety and effectiveness of the CRS-HIPEC combination regime, particularly in cases where HIPEC is used as adjuvant treatment after CRS. Therefore, in the current study, we aimed to evaluate the safety and effectiveness of CRS combined with HIPEC in patients with gastric cancer. METHOD: Data from 231 patients with a median age of 55.1 years treated with the CRS-HIPEC combination regime between January 2009 and December 2014 were retrospectively reviewed. All patients underwent the combination therapy (mean of 2.4 cycles per patient, range, 1 to 4 cycles). RESULTS: Median overall survival was 37.0 months, with 1-, 2- and 3-year survival rates recorded as 83.4%, 68.5%, and 38.7%, respectively. The serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) were significantly decreased after combination therapy in the completeness of cytoreduction (CCR)-0 and CCR-1 groups, while no significant changes observed in marker levels were observed in the CC >=2 group. The post-operative morbidity and mortality rates were 6.9% and 0.9%, respectively. Multivariate analysis revealed low TNM tumour stage, ascites condition and CCR score as independent predictors for better survival. CONCLUSION: In view of the acceptable morbidity and mortality rates we propose that CRS combined with HIPEC presents an effective and safe treatment modality for patients with gastric cancer, especially in cases where optimal cytoreduction is achieved before the HIPEC procedure. PMID- 27362671 TI - A new look MJA. PMID- 27362672 TI - The health of indigenous and tribal peoples across the world: The Lancet-Lowitja Institute Global Collaboration. PMID- 27362669 TI - Proposed New Sub-Grouping for Intermediate-Stage Hepatocellular Carcinoma Using Albumin-Bilirubin Grade. AB - AIM: We retrospectively evaluated the efficacy of albumin-bilirubin (ALBI) grade, which has been proposed as a new classification for hepatic function, for evaluation of the prognosis of intermediate-stage hepatocellular carcinoma (Barcelona Clinic Liver Cancer criteria stage B, BCLC-B). PATIENTS AND METHODS: We enrolled 754 naive BCLC-B patients (multiple tumors) and retrospectively analyzed their clinical features [surgical resection (hepatectomy), n = 170; radiofrequency ablation (RFA), n = 110; percutaneous ethanol injection, n = 7; transcatheter arterial chemoembolization, n = 396; others, n = 25; best supportive care, n = 46]. Four sub-groups were defined for the Modified Intermediate Stage of Liver Cancer (MICAN) criteria as follows: B1 (ALBI-1/within up-to-7 criteria), B2 (ALBI-2/within up-to-7 criteria), B3 (ALBI-1 and ALBI 2/multiple and beyond up-to-7 criteria), and B4 (ALBI-3/any). RESULTS: The median survival time of patients classified as B1 (n = 94), B2 (n = 175), B3 (n = 452), and B4 (n = 33) was 65.1, 48.1, 29.6, and 14.6 months, respectively (p < 0.01 for each). Those in B1 treated with hepatectomy and RFA comprised 67.0%, while that ratio was 51.4% in B2, 28.3% in B3, and 12.1% in B4. CONCLUSION: The MICAN criteria based on ALBI grade are simple and useful for prediction of prognosis and therapy decision-making in the heterogeneous population of BCLC-B patients. PMID- 27362674 TI - Towards an integrated model for child and family services in central Australia. PMID- 27362676 TI - Clinical examination: evidence and eminence. PMID- 27362675 TI - Are Indigenous mortality gaps closing: how to tell, and when? PMID- 27362677 TI - Ankles jerk - yes, but how? PMID- 27362678 TI - Caetano Francisco da Piedade Quadros, MB BCh BAO, DPH, FRACMA, FAFPHM. PMID- 27362679 TI - An insight. PMID- 27362680 TI - We need transformative change in Aboriginal health. PMID- 27362681 TI - Access to contraception for remote Aboriginal and Torres Strait Islander women: necessary but not sufficient. PMID- 27362682 TI - Carers of Indigenous children: services and systems failure? Where to next? PMID- 27362683 TI - Uptake of long-acting, reversible contraception in three remote Aboriginal communities: a population-based study. AB - OBJECTIVE: To assess the use, effectiveness and acceptance of prescribed contraception in three remote Western Australian Aboriginal communities. PARTICIPANTS AND DESIGN: Mixed method study, including retrospective file review of contraception methods for 566 regular female Aboriginal patients, 1 November 2010 - 1 September 2014, and semi-structured interviews with 20 Aboriginal women. SETTING: Primary care clinics in three remote Aboriginal communities. MAIN OUTCOME MEASURES: Number of episodes of contraceptive use, effectiveness and continuation rates of prescribed contraceptive use; personal experiences, attitudes towards and beliefs about contraception options. RESULTS: 34% of women had used contraception, ranging from 15% of women aged younger than 15 years to 55% of women aged 15-19 years. The most common forms of contraception at the census date were long-acting reversible contraceptives (LARCs): 77% of women using contraception had an etonogestrel implant and 7% had depot medroxyprogesterone. Etonogestrel continuation rates at 1, 2 and 3 years were 87% (95% CI, 81-92%), 72% (95% CI, 64-78%) and 51% (95% CI, 41-60%) respectively. Medroxyprogesterone depot continuation at one year was only 14% (95% CI, 8-22%). Social acceptance of the etonogestrel implant was high; no concerns were raised about stigma or unwanted attention related to implant use. CONCLUSION: The high uptake of LARCs in these communities is consistent with international recommendations about contraception use. High acceptability was reflected in excellent continuation rates. Service delivery models that use community engagement and capacity building are recommended for broadening the focus of sexual health beyond sexually transmitted disease detection and management, giving priority to the reproductive rights and unmet needs of Aboriginal women. PMID- 27362684 TI - Psychological distress in carers of Aboriginal children in urban New South Wales: findings from SEARCH (phase one). AB - OBJECTIVE: To examine the factors associated with psychological distress in parents and carers of Aboriginal children living in urban communities in New South Wales. DESIGN: Cross-sectional survey (phase one of the Study of Environment on Aboriginal Resilience and Child Health [SEARCH], November 2007 - December 2011). SETTING AND PARTICIPANTS: Primary care; 589 parents and carers of Aboriginal children were recruited when attending one of the four Aboriginal Community Controlled Health Services (ACCHSs) in urban NSW that participated in SEARCH. MAIN OUTCOME MEASURE: Kessler Psychological Distress Scale (K10) scores; a score of 22 or higher was deemed to indicate high levels of psychological distress. RESULTS: High levels of psychological distress were identified in 18% of our sample. The factors most strongly associated with this distress were functional limitations (v those with K10 scores under 22: adjusted odds ratio [aOR], 4.2; 95% CI, 1.3-13.5), previous hospitalisation (aOR, 5.5; 95% CI, 1.5 19.4) or other treatment for social and emotional wellbeing (aOR, 3.3; 95% CI, 1.3-8.4), low satisfaction with feeling part of the community (aOR, 0.83; 95% CI, 0.70-0.98) and low involvement in clubs and groups (aOR, 2.9; 95% CI, 1.2-7.3). CONCLUSIONS: Clinicians should note that those with functional limitations or a history of treatment for mental health problems are at higher risk of psychological distress and may require additional support. Increased funding that allows ACCHSs to provide mental health services, and funding and promoting programs and activities that increase social connectedness should remain focuses for ACCHSs and policy makers. PMID- 27362685 TI - Increasing Indigenous self-harm and suicide in the Kimberley: an audit of the 2005-2014 data. PMID- 27362687 TI - Pitfalls in photographing radiological images from computer screens. PMID- 27362686 TI - Spirometry reference values in Indigenous Australians: a systematic review. AB - OBJECTIVES: To evaluate published spirometry data for Australian Aboriginal and Torres Strait Islander (Indigenous) peoples to determine (i) whether their ethnicity influenced spirometry results; and (ii) if any reliable spirometry reference values exist for Indigenous Australians. STUDY DESIGN: Systematic review of published and grey literature. DATA SOURCES: PubMed and Cochrane Library databases, references of included articles and appropriate grey literature. Last searches were conducted in April 2016. STUDY SELECTION: We included any study that performed spirometry on healthy Indigenous Australians and compared their results with those from people of European ancestry. Two authors independently screened titles and abstracts and then reviewed potentially relevant full-text articles for possible inclusion. We used PRISMA systematic review reporting methods to collate data. DATA SYNTHESIS: Of a possible 125 studies, 18 full-text articles were reviewed, but only nine fulfilled the inclusion criteria. None specified Torres Strait Islander inclusion. All studies reported lower spirometry values (as much as 30% lower) for Aboriginal people compared with non-Indigenous people. Five studies developed spirometry reference values for Indigenous Australians; however, none adhered to all participant inclusion and exclusion criteria outlined by the American Thoracic Society and European Respiratory Society. Hence, reported results and subsequent reference values may not be a true representation of spirometry values in healthy Indigenous people. CONCLUSIONS: The lower spirometry values reported for Indigenous Australians may be due to study limitations. Furthermore, there are currently no reliable spirometry reference values for Indigenous Australians that adhere to current guidelines. Developing a set of Indigenous Australian reference values will improve the accuracy of test interpretation and aid in the diagnosis of respiratory disease in this population. PMID- 27362688 TI - Pitfalls in photographing radiological images from computer screens. PMID- 27362689 TI - Non-reimbursement for preventable health care-acquired conditions. PMID- 27362690 TI - Non-reimbursement for preventable health care-acquired conditions. PMID- 27362691 TI - The molecular biology of matrix metalloproteinases and tissue inhibitors of metalloproteinases in inflammatory bowel diseases. AB - Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to be predominant proteases and protease inhibitors involved in the pathogenesis of inflammatory bowel diseases (IBD) through their ability to remodel the extracellular matrix (ECM) in response to inflammatory stimuli and by their immunomodulating effects. An imbalance between MMPs and TIMPs has been linked with acute and chronic inflammation and aberrant tissue remodeling, as seen in IBD. Moreover, recurrent phases of tissue destruction and subsequent tissue repair can cause serious complications in IBD patients such as fistulas and fibrosis. The aims of this review are (i) to summarize current literature on genetic association, mRNA, and protein expression studies with regard to MMPs and TIMPs in IBD patients and various animal models, including those with transgenic and knockout mice; (ii) to compare biochemical and molecular biological data in humans with those obtained in animal model studies and (iii) to critically evaluate and translate how this knowledge may be used in practical terms to understand better the pathophysiology and mechanisms operating in IBD and to apply this for improvement of clinical outcomes at diagnostic, prognostic and therapeutic levels. PMID- 27362693 TI - An engineered promoter driving expression of a microbial avirulence gene confers recognition of TAL effectors and reduces growth of diverse Xanthomonas strains in citrus. AB - Xanthomonas citri ssp. citri (X. citri), causal agent of citrus canker, uses transcription activator-like effectors (TALEs) as major pathogenicity factors. TALEs, which are delivered into plant cells through the type III secretion system (T3SS), interact with effector binding elements (EBEs) in host genomes to activate the expression of downstream susceptibility genes to promote disease. Predictably, TALEs bind EBEs in host promoters via known combinations of TALE amino acids to DNA bases, known as the TALE code. We introduced 14 EBEs, matching distinct X. citri TALEs, into the promoter of the pepper Bs3 gene (ProBs31EBE ), and fused this engineered promoter with multiple EBEs (ProBs314EBE ) to either the beta-glucuronidase (GUS) reporter gene or the coding sequence (cds) of the pepper gene, Bs3. TALE-induced expression of the Bs3 cds in citrus leaves resulted in no visible hypersensitive response (HR). Therefore, we utilized a different approach in which ProBs31EBE and ProBs314EBE were fused to the Xanthomonas gene, avrGf1, which encodes a bacterial effector that elicits an HR in grapefruit and sweet orange. We demonstrated, in transient assays, that activation of ProBs314EBE by X. citri TALEs is T3SS dependent, and that the expression of AvrGf1 triggers HR and correlates with reduced bacterial growth. We further demonstrated that all tested virulent X. citri strains from diverse geographical locations activate ProBs314EBE . TALEs are essential for the virulence of X. citri strains and, because the engineered promoter traps are activated by multiple TALEs, this concept has the potential to confer broad spectrum, durable resistance to citrus canker in stably transformed plants. PMID- 27362694 TI - What is the effect of venous thromboembolism and related complications on patient reported health-related quality of life? A meta-analysis. AB - We conducted a meta-analysis of the literature to 1) assess the health-related quality of life for patients with a minimum follow-up of one year after an episode of pulmonary embolism (PE) or deep-vein thrombosis (DVT), and 2) to assess the HRQOL for patients who develop chronic thromboembolic pulmonary hypertension (CTEPH) and post thrombotic syndrome (PTS). PubMed, EMBASE, and the Cochrane Library were searched from inception to March 30, 2016. Data were pooled using random-effects meta-analysis, and heterogeneity was assessed with I2 and Tau2 tests. SF-12, SF-36, and VEINES-QOL were evaluated with pooled standardised mean difference (SMD) and 95 % confidence intervals (CI). Fourteen studies were included for meta-analysis. In patients who sustain a PE, physical health becomes impaired (p<0.001, 2 studies) but mental health appears to remain similar to population norms (p=0.069, 2 studies) after at least one year. Patients who develop CTEPH report worse physical (p<0.001, 1 study) and mental health (p=0.009, 1 study). In patients who suffer from a DVT, physical health (p=0.19, 9 studies), mental health (p=0.67, 9 studies), and disease specific quality of life (p=0.61, 8 studies) remain similar to population norms after at least one year. Patients who develop PTS, however, report worse physical health (p<0.001, 7 studies), mental health (p<0.001, 7 studies), and disease specific quality of life (p<0.001, 10 studies). These data can be used to educate patients during the shared decision making process that increasingly governs medical care today. LEVEL OF EVIDENCE: II. PMID- 27362696 TI - Sonographic Nerve Tracking in the Cervical Region: A Pictorial Essay and Video Demonstration. AB - Imaging of the nerves in the cervical region is more complicated than those of the extremities. Although high-resolution ultrasound enables the depiction of peripheral nerves' morphology and their associations with the adjacent soft tissues, precise identification of the nerves in the neck is still challenging. Familiarization with the cervical nerve tracking techniques can help interventional physiatrists explore/treat relevant entrapment syndromes, so does guiding proper electrode placement during nerve conduction studies. The present article integrates serial ultrasound images and videos to demonstrate how to scan brachial plexus, superficial cervical plexus, cranial nerves in the neck region, and certain branches of the major cervical nerves. PMID- 27362695 TI - Impact of Switching From a Vitamin K Antagonist to Rivaroxaban on Satisfaction With Anticoagulation Therapy: The XANTUS-ACTS Substudy. AB - BACKGROUND: The efficacy, safety, and ease of use of rivaroxaban may reduce anticoagulation-treatment burden and improve nonvalvular atrial fibrillation (NVAF) patient satisfaction compared with vitamin K antagonists (VKAs). HYPOTHESIS: Transitioning from a VKA to rivaroxaban improves treatment satisfaction in routine practice. METHODS: Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation (XANTUS) is a prospective, noninterventional study in patients with NVAF prescribed rivaroxaban for prevention of stroke in routine practice. Patients receiving a VKA 4 weeks prior to the initial XANTUS study visit and switched to rivaroxaban were asked to complete the Anti-Clot Treatment Scale (ACTS). Changes from the initial visit to the first follow-up visit at ~ 3 months (corresponding to a comparison of rivaroxaban vs prior VKA) for ACTS burden and benefit scores were calculated using and reported as least squared mean differences (LSMDs) with 95% confidence intervals (CIs). RESULTS: The study included 1291 NVAF patients with prior VKA treatment. The mean baseline ACTS burden and benefit scores were 50.51 +/- 8.42 and 10.30 +/- 2.70, respectively. After ~ 3 months of rivaroxaban treatment, LSMDs were 4.38 points (95% CI: 2.53-6.22, P < 0.0001) for the burden and 1.01 points (95% CI: 0.27 1.75, P = 0.0075) for the benefit score. Fifty-four percent and 48% of patients reported experiencing at least a minimally important clinical difference in burden and benefit scores, respectively. CONCLUSIONS: Within this XANTUS cohort, switching from a VKA to rivaroxaban yielded statistically and clinically significant improvements in ACT burden and benefit scores. PMID- 27362697 TI - High Intensity Aerobic and Resistance Exercise Can Improve Glucose Tolerance in Persons With Multiple Sclerosis: A Randomized Controlled Trial. AB - INTRODUCTION: The prevalence of impaired glucose tolerance (IGT) is higher in persons with multiple sclerosis (MS) compared to healthy controls, indicating metabolic deficits that may increase comorbidity. In other populations, IGT can, at least partly, be reversed by intense physical exercise, but this is never investigated before in MS. AIM: To investigate the effect of high intensity aerobic and resistance training on glucose tolerance and skeletal muscle GLUT4 content in MS. METHODS: Thirty-four persons with MS (aged 45 +/- 3 years, EDSS 2.5 +/- 1.07) were randomized into three groups, including a (1) sedentary control group (SED, n = 11), (2) 12-week high intensity interval plus resistance training group (HITR, n = 12), or (3) 12-week high intensity continuous aerobic training plus resistance training group (HCTR, n = 11). Before and after 12 weeks, glucose tolerance and skeletal muscle GLUT4 content were determined by an oral glucose tolerance test and analysis of a m.vastus lateralis biopsy, respectively. RESULTS: There were no significant changes for subjects of SED. From pre- to post-intervention, total area under the glucose curve (tAUC) decreased significantly in both HITR (-6.9 +/- 6.2%) and HCTR (-11.0 +/- 7.7%) (P < 0.05). Insulin tAUC decreased (-12.3 +/- 14.7%) within HCTR and muscle GLUT4 content increased (+6.6 +/- 4.5%) in HITR. CONCLUSION: Twelve weeks of high intensity aerobic exercise in combination with resistance training improved glucose tolerance in persons with MS. PMID- 27362698 TI - Vasculitic Mononeuritis Multiplex May Be Misdiagnosed as Carpal Tunnel Syndrome. AB - Vasculitis is a group of disorders characterized by inflammation and destruction of blood vessels, resulting in ischemic injury to the involved tissue. Sometimes, peripheral neuropathy is one of the first symptoms of systemic vasculitis. Although the classic form of peripheral nervous system vasculitis is mononeuritis multiplex, it can also present as a mononeuritis. In this case report, the patient presented with progressive rapid onset numbness in her right hand for 2 months. She underwent carpal tunnel decompression surgery with initial diagnosis of acute carpal tunnel syndrome but failed to respond to the surgery, and two month later, she presented with foot drop. The final diagnosis was vasculitic mononeuritis multiplex. The present case report demonstrates the importance of identification of median mononeuritis as one of the first presentations of vasculitic disorders and distinction from acute carpal tunnel syndrome. The natural history of many of the systemic vasculitides is rapidly progressive, and they are likely to be fatal without early treatment. In this regard, timely diagnosis of vasculitis is critical because of the vital role of early immunosuppressive therapy in preventing multiorgan damage and decreasing mortality rate. PMID- 27362701 TI - Prevalence and Characteristics of Body Dysmorphic Disorder Among Patients in a Partial Hospital Program. AB - Body dysmorphic disorder (BDD) is a common disorder that is usually associated with impaired functioning and high levels of suicidality. The current study is the first to assess prevalence of BDD among patients in a partial hospital program and compare patients with and without BDD on demographic and clinical variables. Participants were 207 patients with a variety of Axis I diagnoses. Prevalence of current BDD was 7.2%, and a diagnosis of BDD did not predict worse treatment outcome in the program. Patients with current BDD were more likely to be female and younger and have more comorbid diagnoses than patients without current BDD. No other significant differences were found at baseline between patients with and without current BDD. Results indicate that BDD is relatively common among patients in partial hospital programs and that such programs may be as beneficial to patients with BDD as to other patients. PMID- 27362702 TI - Gender Dysphoria and Psychiatric Symptoms. PMID- 27362703 TI - Phenylephrine Decreases Vascular Tension in Goat Arteries in Specific Circumstances. AB - Phenylephrine (PE) causes vasoconstriction through alpha adrenergic receptors. PE induced vasodilatation has also been reported earlier in pre-constricted vessels. Here we demonstrate in spiral strips of goat arteries that addition of PE can decrease tone even from base-line levels (i.e. not pre-constricted) and show that this process requires nitric oxide (NO) and alpha adrenergic stimulation, but is cGMP-independent. Under control conditions, PE caused vasoconstriction, but under conditions where NO levels are higher, as with L-Arginine or sodium nitroprusside, PE decreased vessel tension. L-Arginine/PE combination was not able to decrease tension when alpha adrenoceptors were blocked with Phentolamine or endothelial nitric oxide synthase (eNOS) was blocked with Nomega-Nitro-L arginine (L-NNA). Propranolol, a beta blocker, was unable to prevent the reduction in tension by the L-Arginine/PE combination. Adrenaline and noradrenaline (and not isoproterenol) also reduced vessel tension in the presence of L-Arginine. Even when NO levels were not enhanced, relieving NO from having to stimulate the enzyme soluble guanylyl cyclase (sGC) (either by using sGC blockers, namely ODQ or methylene blue, or by enhancing cGMP levels (with sildenafil) which by negative feedback probably inhibits sGC) led to PE-induced reduction of vascular tension. PMA-phorbol myristate acetate-an agonist which stimulates Protein Kinase C was able to prevent the ability of PE to reduce vascular tension in a high NO environment. Our conclusion is that PE reduces vascular tension through alpha adrenoceptors if there is excess NO availability to activate a putative pathway. Though the reduction of vessel tone by PE is dependent on NO, it is independent of cGMP. Prior treatment with PMA or PE itself can prevent further PE-induced reduction of tension in a high NO environment. The results here suggest, counter-intuitively, that alpha blockers may be of help in the treatment of septic shock where nitric oxide levels are high. PMID- 27362704 TI - OMIP-034: Comprehensive immune phenotyping of human peripheral leukocytes by mass cytometry for monitoring immunomodulatory therapies. PMID- 27362705 TI - A Two-Year Randomized Trial of Interventions to Decrease Stress Hormone Vasopressin Production in Patients with Meniere's Disease-A Pilot Study. AB - Meniere's disease, a common inner ear condition, has an incidence of 15-50 per 100,000. Because mental/physical stress and subsequent increase in the stress hormone vasopressin supposedly trigger Meniere's disease, we set a pilot study to seek new therapeutic interventions, namely management of vasopressin secretion, to treat this disease. We enrolled 297 definite Meniere's patients from 2010 to 2012 in a randomized-controlled and open-label trial, assigning Group-I (control) traditional oral medication, Group-II abundant water intake, Group-III tympanic ventilation tubes and Group-IV sleeping in darkness. Two hundred sixty-three patients completed the planned 2-year-follow-up, which included assessment of vertigo, hearing, plasma vasopressin concentrations and changes in stress/psychological factors. At 2 years, vertigo was completely controlled in 54.3% of patients in Group-I, 81.4% in Group-II, 84.1% in Group-III, and 80.0% in Group-IV (statistically I < II = III = IV). Hearing was improved in 7.1% of patients in Group-I, 35.7% in Group-II, 34.9% in Group-III, and 31.7% in Group-IV (statistically I < II = III = IV). Plasma vasopressin concentrations decreased more in Groups-II, -III, and -IV than in Groups-I (statistically I < II = III = IV), although patients' stress/psychological factors had not changed. Physicians have focused on stress management for Meniere's disease. However, avoidance of stress is unrealistic for patients who live in demanding social environments. Our findings in this pilot study suggest that interventions to decrease vasopressin secretion by abundant water intake, tympanic ventilation tubes and sleeping in darkness is feasible in treating Meniere's disease, even though these therapies did not alter reported mental/physical stress levels. TRIAL REGISTRATION: ClinicalTrials.gov NCT01099046. PMID- 27362706 TI - Histone deacetylase inhibition, but not a mineralocorticoid receptor antagonist spironolactone, attenuates atypical transcription by an activating mutant MR (MRS 810L ). AB - A mutation in the mineralocorticoid receptor (MRS 810L ) leads to early-onset hypertension, which is markedly exacerbated during pregnancy. The mutation causes progesterone and even the MR antagonist spironolactone to become potent agonists. Thus, it is hard to control hypertension in patients harbouring this mutation. We hypothesized that histone deacetylase inhibition (HDACi), but not the MR antagonist spironolactone, attenuates atypical transcriptional activity of activating mutant MR (MRS 810L ). We established HEK293T cells overexpressing wild-type MR (MRWT ) or MRS 810L and determined their transcriptional activities by luciferase assay. Expression of MR target genes was measured by quantitative real-time PCR (qRT-PCR). Treatment with aldosterone increased the expression of MR target genes as well as the transcriptional activities in HEK293T cells transfected either with MRWT or MRS 810L . Treatment with either spironolactone or progesterone also increased the expression of MR target genes as well as transcriptional activity, but only in HEK293T cells transfected with MRS 810L . Spironolactone abolished the promoter activity stimulated by aldosterone in HEK293T cells transfected with MRWT . Treatment with HDAC inhibitors attenuated the transcriptional activity as well as the expression of MR target genes induced by aldosterone, spironolactone, or progesterone whether HEK293T cells were transfected with either MRWT or MRS 810L . These results indicate that HDACi, but not an MR antagonist spironolactone, attenuates atypical transcriptional activity of an activating mutant MR (MRS 810L ). PMID- 27362707 TI - Enhanced startle responsivity 24 hours after acute stress exposure. AB - Cortisol release in a stressful situation can be beneficial for memory encoding and memory consolidation. Stimuli, such as odors, related to the stressful episode may successfully cue memory contents of the stress experience. The current investigation aimed at testing the potency of stress to influence startle responsivity 24 hr later and to implicitly reactivate emotional memory traces triggered by an odor involved. Participants were assigned to either a stress (Trier Social Stress Test [TSST]) or control (friendly TSST [f-TSST]) condition featuring an ambient odor. On the next day, participants underwent an auditory startle paradigm while their eyeblink reflex was recorded by an electrooculogram. Three different olfactory stimuli were delivered, one being the target odor presented the day before. Additionally, negative, positive, and pictures of the committee members were included for comparing general startle responsivity and fear-potentiated startle. Participants of the stress group demonstrated an enhanced startle response across all stimuli compared to participants of the control group. There were no specific effects with regard to the target odor. The typical fear-potentiated startle response occurred. Stressed participants tended to rate the target odor more aversive than control participants. Odor recognition memory did not differ between the groups, suggesting an implicit effect on odor valence. Our results show that acute stress exposure enhances startle responsivity 24 hr later. This effect might be caused by a shift of amygdala function causing heightened sensitivity, but lower levels of specificity. (PsycINFO Database Record PMID- 27362708 TI - Factors Influencing Bacterial Diversity and Community Composition in Municipal Drinking Waters in the Ohio River Basin, USA. AB - The composition and metabolic activities of microbes in drinking water distribution systems can affect water quality and distribution system integrity. In order to understand regional variations in drinking water microbiology in the upper Ohio River watershed, the chemical and microbiological constituents of 17 municipal distribution systems were assessed. While sporadic variations were observed, the microbial diversity was generally dominated by fewer than 10 taxa, and was driven by the amount of disinfectant residual in the water. Overall, Mycobacterium spp. (Actinobacteria), MLE1-12 (phylum Cyanobacteria), Methylobacterium spp., and sphingomonads were the dominant taxa. Shifts in community composition from Alphaproteobacteria and Betaproteobacteria to Firmicutes and Gammaproteobacteria were associated with higher residual chlorine. Alpha- and beta-diversity were higher in systems with higher chlorine loads, which may reflect changes in the ecological processes structuring the communities under different levels of oxidative stress. These results expand the assessment of microbial diversity in municipal distribution systems and demonstrate the value of considering ecological theory to understand the processes controlling microbial makeup. Such understanding may inform the management of municipal drinking water resources. PMID- 27362710 TI - Cell cycle-arrested cells know the right time. PMID- 27362709 TI - Rapid and Non-destructive Detection and Identification of Two Strains of Wolbachia in Aedes aegypti by Near-Infrared Spectroscopy. AB - The release of Wolbachia infected mosquitoes is likely to form a key component of disease control strategies in the near future. We investigated the potential of using near-infrared spectroscopy (NIRS) to simultaneously detect and identify two strains of Wolbachia pipientis (wMelPop and wMel) in male and female laboratory reared Aedes aegypti mosquitoes. Our aim is to find faster, cheaper alternatives for monitoring those releases than the molecular diagnostic techniques that are currently in use. Our findings indicate that NIRS can differentiate females and males infected with wMelPop from uninfected wild type samples with an accuracy of 96% (N = 299) and 87.5% (N = 377), respectively. Similarly, females and males infected with wMel were differentiated from uninfected wild type samples with accuracies of 92% (N = 352) and 89% (N = 444). NIRS could differentiate wMelPop and wMel transinfected females with an accuracy of 96.6% (N = 442) and males with an accuracy of 84.5% (N = 443). This non-destructive technique is faster than the standard polymerase chain reaction diagnostic techniques. After the purchase of a NIRS spectrometer, the technique requires little sample processing and does not consume any reagents. PMID- 27362711 TI - Advantages of robotics in benign gynecologic surgery. AB - PURPOSE OF REVIEW: The purpose of this article is to review the literature and discuss the advantages of robotics in benign gynecologic surgery. RECENT FINDINGS: Minimally invasive surgery has become the preferred route over abdominal surgery. The laparoscopic or robotic approach is recommended when vaginal surgery is not feasible. Thus far, robotic gynecologic surgery data have demonstrated feasibility, safety, and equivalent clinical outcomes in comparison with laparoscopy and better clinical outcomes compared with laparotomy. Robotics was developed to overcome challenges of laparoscopy and has led to technological advantages such as improved ergonomics, visualization with three-dimensional capabilities, dexterity and range of motion with instrument articulation, and tremor filtration. To date, applications of robotics in benign gynecology include hysterectomy, myomectomy, endometriosis surgery, sacrocolpopexy, adnexal surgery, tubal reanastomosis, and cerclage. Though further data are needed, robotics may provide additional benefits over other approaches in the obese patient population and in higher complexity cases. Challenges that arose in the earlier adoption stage such as the steep learning curve, costs, and operative times are becoming more optimized with greater experience, with implementation of robotics in high volume centers and with improved training of surgeons and robotic teams. Robotic laparoendoscopic single-site surgery, albeit still in its infancy where technical advantages compared with laparoscopic single-site surgery are still unclear, may provide a cost-reducing option compared with multiport robotics. The cost may even approach that of laparoscopy while still conferring similar perioperative outcomes. SUMMARY: Advances in robotic technology such as the single-site platform and telesurgery, have the potential to revolutionize the field of minimally invasive gynecologic surgery. Higher quality evidence is needed to determine the advantages and disadvantages of robotic surgery in benign gynecologic surgery. Conclusions on the benefits and risks of robotic surgery should be made with caution given limited data, especially when compared with other routes. Route of surgery selection should take into consideration the surgeons' skill and comfort level that allows for the highest level of safety and efficiency. Ultimately, the robotic device is an additional minimally invasive surgical tool that can further the goal of minimizing laparotomy in gynecology. PMID- 27362713 TI - A Major Advance in the Synthesis of Fluoroalkyl Pyrazoles: Tuneable Regioselectivity and Broad Substitution Patterns. AB - A novel approach towards highly functionalized fluoroalkyl pyrazoles was developed by using fluoroalkyl amino reagents in combination with a variety of fluorinated ketimines. Tuneable introduction of fluoroalkyl groups in the 3- and 5-positions was possible by using vinamidinium intermediates or the corresponding enamino ketones after hydrolysis. These high-value building blocks can give rise to a large number of analogues for bioactivity screening and discovering new heterocyclic bioactive ingredients in various life science fields. PMID- 27362712 TI - The effect of epidermal levels of urocanic acid on 25-hydroxyvitamin D synthesis and inflammatory mediators upon narrowband UVB irradiation. AB - BACKGROUND/PURPOSE: Urocanic acid (UCA) absorbs ultraviolet (UV)B radiation in the epidermis which may interfere with phototherapy. Therefore, the influence of individual levels of UCA on immune reactivity and vitamin D synthesis induced by narrowband UVB radiation was assessed. METHODS: Twenty-eight subjects with irritant contact dermatitis of the hands were irradiated with suberythemal doses of narrowband UVB radiation on their unaffected lower forearms on three consecutive days. Stratum corneum tape strips and epidermal interstitial fluid (ISF) as well as blood samples were analyzed. RESULTS: Narrowband UVB irradiation led to the conversion of trans-UCA into its cis-isomer in the epidermis. The observed increase in 25-hydroxyvitamin D serum concentrations was inversely correlated with the baseline levels of trans-UCA. Furthermore, UVB irradiation induced significant changes in the levels of CXCL10/IP-10, CCL2/MCP-1, CCL4/MIP 1beta, and the IL-1RA/IL-1alpha ratio. The levels of IL-1alpha and CXCL9/MIG showed a trend toward increase. The changes in the levels of inflammatory and immunomodulatory mediators did not depend on baseline levels of trans-UCA. CONCLUSION: The results suggest that epidermal levels of trans-UCA affect vitamin D synthesis, but not cutaneous immune reactivity upon repeated exposure to suberythemal doses of narrowband UVB radiation. However, this requires further exploration. PMID- 27362715 TI - [Not Available]. PMID- 27362714 TI - The combined use of three widely available biochemical markers as predictor of organ failure in critically ill patients. AB - BACKGROUND: We hypothesized that lactate dehydrogenase, LDH/albumin ratio in combination with or without magnesium (Mg(2+)) could predict organ failure in critically ill adult patients. The aim of this study was to describe a new risk index for organ failure or mortality in critically ill patients based on a combination of these routinely available biochemical plasma biomarkers. METHODS: Patients >= 18 years admitted to the intensive care unit (ICU) were screened. Albumin and LDH were analyzed at the time of admission to ICU (n = 347). Organ failure assessed with 'Sequential Organ Failure Assessment' (SOFA) score was used, and 30-day mortality was recorded. The predictive value of the test was calculated using the areas under the receiving operating characteristic (ROC) curve. RESULTS: The LDH/albumin ratio was higher in patients who developed organ failure as compared to those who did not (p < 0.001). The areas under the ROC curve were 0.77 both for prediction of multiple organ failure and for 30-day mortality. In a subgroup of patients (n = 183) admitted to ICU from the emergency department, the predictive values were 0.86 and 0.80, respectively. CONCLUSION: The LDH/albumin ratio at ICU admission was associated with the development of multiple organ failure and 30-day mortality in this prospective study. The clinical value of this biomarker as a predictor of organ failure in critically ill patients is yet to be defined. PMID- 27362716 TI - [Gastroenterology towards 2020]. AB - Research in gastroenterology and hepatology is booming. The spectrum of digestive diseases is very extensive, and growing. This issue of the journal focuses on the near future of gastreonterology, and announces what changes should we expect between now and 2020. The next number will be devoted to changes in hepatology. PMID- 27362717 TI - [First part: the intestinal microbiota]. AB - The human gastrointestinal tract contains a large number of commensal (non pathogenic) and pathogenic microbial species that have co-evolved with the human genome and differ in composition and function based on their location, as well as age, sex, race/ethnicity, and diet of their host and we can in fact consider the human body as a mix of human and bacterial cells. It is now evident that the large intestine is much more than an organ for waste material and absorption of water, salts and drugs, and indeed has a very important impact on human health, for a major part related to the specific composition of the complex microbial community in the colon. In man, the large gut receives material from the ileum which has already been digested and the contents are then mixed and retained for 6-12 hours in the caecum and right colon. Thus, the large intestine is an open system, with nutrients flowing in the caecum, and bacteria, their metabolic products, and undigested foodstuffs being excreted as faeces. The anaerobic brakdown of carbohydrate and protein by bacteria is known conventionally as fermentation. In man the major end products are the short-chain fatty acids (SCFA) acetate, propionate, butirate, the gases H2 and CO2, ammonia, amines, phenols and energy, which the bacteria use for growth and the maintenance of cellular function. The microbiota is also an important factor in the development of the immune response. The interaction between the gastrointestinal tract and resident microbiota is well balanced in healthy individuals, but its breakdown can lead to intestinal and extraintestinal disease. PMID- 27362718 TI - [Probiotics]. AB - On the basis of the currently available literature, which includes well-designed clinical trials, systematic reviews and meta-analyses, certain effects can be ascribed to probiotics as a general class. It is accepted that sufficient evidence has accumulated to support the concept of benefits of certain probiotics; it is reasonable to expect that evidence gained from a defined class of live microbes might be appropriate for certain, but not all, health outcomes. Moreover there is a need for clear communication to consumers and health-care providers of the activity of differentiate probiotic products. PMID- 27362719 TI - [Upper and lower gastrointestinal endoscopy]. AB - Recent-years technological innovation has achieved two important objectives: 1) to develop advanced diagnostic tools able to determine with a fair degree of accuracy the nature of a lesion by means of the simple endoscopic observation; 2) to improve the therapeutic approach to lesions, by extending the least-invasive endoscopic treatment also to lesions that in the past were referred to surgery. Advanced diagnostic methodologies have been achieved thanks to the introduction of high definition endoscopes and virtual chromo-endoscopy. Therapeutic innovation is represented by endoscopic sub-mucosal dissection (ESD) that enables the "en bloc" resection of the lesions, thus ensuring a more accurate histological evaluation of their level of infiltration and of the radicality of the resection. These diagnostic and therapeutic methodologies have been applied intensively in Barrett's esophagus, in the early gastric cancer and in the neoplastic lesions of colon-rectum. Concerning the screening of colon-rectum cancer, recent-years literature concentrated on defining the minimal necessary requirements to perform an effective and safe colonoscopy, the so-called "quality endoscopy", for which reference indicators and standards have been set. PMID- 27362720 TI - [Digestive endoscopy: biliary tract and pancreas]. AB - New technological developments in endoscopic retrograde cholangiopancreatography and endoscopic ultrasound, both for diagnosis and treatment of biliary and pancreatic diseases, have opened up new scenarios in the recent years. For instance, removal of large bile duct stones with endoscopic sphincterotomy followed by large balloon dilation has been proven to be a safe and effective technique. Also cholangioscopy evolved in terms of better imaging, tissue acquisition and stones management. Self-expandable metal stents are used mostly for malignant diseases, but their role in benign diseases has also been deeply investigated in the last years. The rapid evolution in the field of radiofrequency brought new devices for safer ablation and palliation of biliary tumours. Self-expandable metal stents are also used for ultrasound-guided drainage of walled off pancreatic necrosis and for choledocoduodenostomy and cholecystogastrostomy. PMID- 27362721 TI - [IBD: Crohn's disease]. AB - Crohn's disease (CD) is a chronic inflammatory disorder that primarily affects small intestine and colon and causes tissue damage. The aetiology of CD is unknown, but a large body of evidence suggests that the pathological process is driven by excessive immune response, which is direct against components of the luminal flora and sustained by defects in counter-regulatory mechanisms. CD is a transmural progressive and destructive disease leading to irreversible bowel damage characterized by stenosis of the intestinal lumen and penetrating lesions such as fistulas and abscesses. The goals of medical therapy in CD are to: 1) induce symptomatic remission; 2) maintain steroid-free remission; 3) enhance quality of life; 4) prevent/treat complications of disease; 5) avoid short and long term toxicity of therapy. Achieving these goals requires a sophisticated approach that tailors therapy to each patient, involving attempts to risk stratify the patient, optimizing each therapy, and monitoring for objective evidence of resolution of inflammation. Although the number of medications available to treat CD has increased in the last 15 years, with the important addition of biologic therapies, including anti-TNF antibodies such as infliximab, adalimumab, and certolizumab pegol, and more recently, vedolizumab, an anti alpha4beta7 integrin antibody, the number of agents remains relatively small. PMID- 27362722 TI - [Ulcerative colitis]. AB - Inflammatory bowel disease (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing inflammatory disorders of the digestive tract resulting from dysregulated immune responses toward environmental factors in genetically predisposed individuals. This review focus on what is the state of the art of UC pathophysiology, diagnosis, and treatment and how any future findings could drive our clinical practice. PMID- 27362723 TI - [Diverticular disease: towards 2020. An evidence-based approach]. AB - Diverticular disease (DD) of the colon has an increasing burden on health service resources, in terms of hospital admissions, mortality and surgery rate. We present an overview of the clinical history of DD, and of the ways that gastroenterologists have to modify it. Prevalence of the disease increases with aging. Most of diverticulosis are occasionally identified on colonscopy, and most of them remain asymptomatic for all life. Only 4% of these subjects develop diverticulitis. However, 4-25% of these patients are expected to present a second episode of diverticulitis, and 15% of them develop complications. Hospitalizations for diverticulitis and relapses of diverticulitis show strong growth (+21% 2013 vs 2003 in USA). The total annual costs for hospitalization for DD in USA are over 2,2 billion of dollars, and in Italy exceed 63 million of euros. In-hospital mortality can reach 0,5%. Diagnosis of diverticulitis is based on clinical history, lab tests and imaging (ultrasonography, CAT). Clinical diagnosis has a sensitivity of 68% and specificity around 98%. According to a meta-analysis, the performance of ultrasonograhy and CAT results very high ("pooled" sensitivity 92-94%, and specificity 90-99%; "pooled" Likelihood Ratio positive 9.6 for ultrasonography and 78.4 for CAT. Likelihood Rato negative 0.09 and 0.06 respectively). Evidences for preventing relapse are poor. Anyway, a very recent meta-analysis on 6 RCTs suggests no role for mesalazine (GRADE SCALE for evidence 3). Non absorbable antibiotics (rifaximin) have been used in two studies (one RCT, one retrospective observational). Data from the two studies suggest some evidence in favour of its use (GRADE SCALE 1). The number of admitted patients is 291. Considering a base-line risk of 19 relapses every 100 patients (5-year observation period), the absolute risk difference is minus 9 patients with relapse (CI 95% -14 a + 3) in the RCT and minus 14 patients (CI 95% -17 a 5) in the observational study. A 2020 preview suggests an exploding interest in assessing the risk factors for relapse (including aspirin and NSAIDs) and identifying the better strategy to reduce it. Further trials are requested, including the use of probiotics alone. PMID- 27362724 TI - [Design of a genomic, environmental, microbial and metabolomic study on celiac disease: an approach to the future of personalized prevention of celiac disease]. AB - Over recent years we have seen rising many clinical and scientific innovations about celiac disease (CE), however the most important innovation that will contribute to change the future of the research and clinic in this field is the natural history of the disease. For many years it has been though that a genetic predisposition and the exposure to gluten were necessary and sufficient to develop CE. Recent studies, however, suggest that the loss of tolerance to gluten may occur in any moment of life upon certain conditions. Furthermore, several environmental factors known to play a role in shaping the intestinal microflora have also been considered related to the development of CE. Delivery mode, the infant diet and the use of antibiotics are included among these factors. To this day no large scale studies have determined if and how the microbiome composition and its metabolomic profile may influence the loss of tolerance to gluten and the consequent development of CE. In this paper we describe a prospective, multi centric and longitudinal study on infants at risk for CE that will use different techniques to better understand the role of the microbome during the first steps in the development of the autoimmune disease. PMID- 27362725 TI - [Epidemiology, clinical features and treatment of chronic pancreatitis: current knowledge and future perspectives]. AB - Chronic pancreatitis is a complex disease both for the epidemiology, with uncertain data on the exact prevalence, but also for the etiology, often not identified and for whom, compared to the past, post acute pancreatitis forms are showing a high impact; also smoking is an etiological factor often underestimated compared to alcohol. Chronic pancreatitis is associated with high mortality and morbidity, mostly due to extrapancreatic diseases. The eventual occurrence of exocrine or endocrine pancreatic insufficiency can lead to complications, often serious and not prevented in time. It is, in fact, well known how this can cause micro or macronutrient and vitamin deficit which, if not screened and corrected, can cause complications such as osteoporosis. Abdominal pain is the most relevant symptom, with a complex pathogenesis, due not only to obstructive or mechanical factors or inflammation, but also to a chronic alteration of the adaptation process of pain in the central nervous system. Also for this reason, therapies are often not effective. Derivative surgery is indicated in obstructive forms, with results superior to those of endoscopy, while resective surgery is indicated when an inflammatory mass is present. A new opportunity is total pancreatectomy with islet autotransplantation, which offers excellent results in terms of pain relief and possibility to avoid diabetes in a high percentage of patients. This review will discuss these hot topics comprehending both most recent evidence and a view on how our knowledge on this disease will change in the upcoming years. PMID- 27362726 TI - [Pancreatic cancer]. AB - Pancreatic cancer is the fourth leading cause of death for neoplasm in western countries. Surgery still remains the treatment of choice although almost 80% of patients are not resectable at diagnosis because of liver metastases and the 5 year overall survival of patients treated with surgery is only (20%). During the last two decades we have witnessed an overall improvement in terms of survival, mostly due to the advances in therapy and strategies for a more accurate patient selection for surgery. Specific preoperative criteria, mostly linked to the biological features of the tumour, have been proposed to better identify those patients who will benefit from surgical resection, such as duration of symptoms and serum level of CA19-9 in resectable disease. Oncological therapy plays a central role in the management of pancreatic cancer. In patients undergone surgical resection, adjuvant therapy might increase the overall survival and reduce the rate of early relapse. Patients with locally advanced pancreatic cancer can be treated with neoadjuvant treatment. Chemotherapy or chemoradiotherapy are usually used with the aim to downstage the disease but whether one specific strategy or drug is the treatment of choice is still under debate. PMID- 27362727 TI - [Not Available]. PMID- 27362728 TI - Monodisperse Mesoporous Carbon Nanoparticles from Polymer/Silica Self-Aggregates and Their Electrocatalytic Activities. AB - In our quest to make various chemical processes sustainable, the development of facile synthetic routes and inexpensive catalysts can play a central role. Herein we report the synthesis of monodisperse, polyaniline (PANI)-derived mesoporous carbon nanoparticles (PAMCs) that can serve as efficient metal-free electrocatalysts for the hydrogen peroxide reduction reaction (HPRR) as well as the oxygen reduction reaction (ORR) in fuel cells. The materials are synthesized by polymerization of aniline with the aid of (NH4)2S2O8 as oxidant and colloidal silica nanoparticles as templates, then carbonization of the resulting PANI/silica composite material at different high temperatures, and finally removal of the silica templates from the carbonized products. The PAMC materials that are synthesized under optimized synthetic conditions possess monodisperse mesoporous carbon nanoparticles with an average size of 128 +/- 12 nm and an average pore size of ca. 12 nm. Compared with Co3O4, a commonly used electrocatalyst for HPRR, these materials show much better catalytic activity for this reaction. In addition, unlike Co3O4, the PAMCs remain relatively stable during the reaction, under both basic and acidic conditions. The nanoparticles also show good electrocatalytic activity toward ORR. Based on the experimental results, PAMCs' excellent electrocatalytic activity is attributed partly to their heteroatom dopants and/or intrinsic defect sites created by vacancies in their structures and partly to their high porosity and surface area. The reported synthetic method is equally applicable to other polymeric precursors (e.g., polypyrrole (PPY)), which also produces monodisperse, mesoporous carbon nanoparticles in the same way. The resulting materials are potentially useful not only for electrocatalysis of HPRR and ORR in fuel cells but also for other applications where high surface area, small sized, nanostructured carbon materials are generally useful for (e.g., adsorption, supercapacitors, etc.). PMID- 27362729 TI - Quantitation of Aristolochic Acids in Corn, Wheat Grain, and Soil Samples Collected in Serbia: Identifying a Novel Exposure Pathway in the Etiology of Balkan Endemic Nephropathy. AB - While to date investigations provided convincing evidence on the role of aristolochic acids (AAs) in the etiology of Balkan endemic nephropathy (BEN) and upper urothelial cancer (UUC), the exposure pathways by which AAs enter human bodies to cause BEN and UUC remain obscure. The goal of this study is to test the hypothesis that environmental pollution by AAs and root uptake of AAs in the polluted soil may be one of the pathways by which AAs enter the human food chain. The hypothesis driving this study was that the decay of Aristolochia clematitis L., a AA-containing herbaceous plant that is found growing widespread in the endemic regions, could release free AAs to the soil, which could be taken up by food crops growing nearby, thereby transferring this potent human nephrotoxin and carcinogen into their edible parts. Using the highly sensitive and selective high performance liquid chromatography coupled with fluorescence detection method, we identified and quantitated in this study for the first time AAs in corn, wheat grain, and soil samples collected from the endemic village Kutles in Serbia. Our results provide the first direct evidence that food crops and soil in the Balkans are contaminated with AAs. It is possible that the presence of AAs in edible parts of crops originating from the AA-contaminated soil could be one of the major pathways by which humans become exposed to AAs. PMID- 27362731 TI - Increasing Stability and Activity of Core-Shell Catalysts by Preferential Segregation of Oxide on Edges and Vertexes: Oxygen Reduction on Ti-Au@Pt/C. AB - We describe a new class of core-shell nanoparticle catalysts having edges and vertexes covered by refractory metal oxide that preferentially segregates onto these catalyst sites. The monolayer shell is deposited on the oxide-free core atoms. The oxide on edges and vertexes induces high catalyst stability and activity. The catalyst and synthesis are exemplified by fabrication of Au nanoparticles doped by Ti atoms that segregate as oxide onto low-coordination sites of edges and vertexes. Pt monolayer shell deposited on Au sites has the mass and specific activities for the oxygen reduction reaction about 13 and 5 times higher than those of commercial Pt/C catalysts. The durability tests show no activity loss after 10 000 potential cycles from 0.6 to 1.0 V. The superior activity and durability of the Ti-Au@Pt catalyst originate from protective titanium oxide located at the most dissolution-prone edge and vertex sites and Au supported active and stable Pt shell. PMID- 27362730 TI - Cancer cell-derived 12(S)-HETE signals via 12-HETE receptor, RHO, ROCK and MLC2 to induce lymph endothelial barrier breaching. AB - BACKGROUND: The arachidonic acid metabolite 12(S)-HETE is suspected to enhance metastatic spread by inducing cancer cell- and lymph endothelial cell (LEC) motility. However, the molecular mechanisms leading to 12(S)-HETE-triggered cell migration are still elusive. METHODS: To delineate the signalling pathways involved in 12(S)-HETE-mediated migration, inhibitors against RHO and ROCK, and specific siRNAs downregulating 12(S)-HETE receptor (12-HETER) and myosin light chain 2 (MLC2) were used. The breaching of the endothelial barrier was investigated by an assay measuring tumour spheroid-triggered 'circular chemorepellent-induced defects' (CCIDs), and respective signal transduction was elucidated by western blotting. RESULTS: We provide evidence that 12(S)-HETE phosphorylated (and activated) MLC2, which regulates actin/myosin-based contraction. MLC2 activation was found to be essential for LEC retraction and CCID formation. Furthermore, we show that 12(S)-HETE activated a 12-HETER-RHO ROCK-MYPT signalling cascade to induce MLC2 function. CONCLUSIONS: Signalling via this pathway is described for this metabolite for the first time. This may provide potential targets for the intervention of metastatic colonisation. PMID- 27362732 TI - Examination of postures and frequency of musculoskeletal disorders among manual workers in Calcutta, India. AB - BACKGROUND: Manual material handling (MMH) activities require workers to adopt various awkward postures leading to the development of musculoskeletal disorders (MSD). OBJECTIVES: To investigate the postures adopted during heavy load handling and the frequency of MSDs among MMH workers in Calcutta, India. METHODS: We conducted a cross-sectional study with 100 MMH workers. MSD frequency was assessed via the Standardized Nordic Questionnaire. The Ovako Working Posture Assessment System (OWAS) was used to analyze working posture. We used logistic regression to predict MSD risk factors. RESULTS: Ninety five percent of workers reported a MSD in at least one body part in the past 12 months. According to OWAS results, 83% of the analysed work postures require immediate corrective measures for worker safety. The most harmful posture was carrying a heavy load overhead. Carrying more than 120 kg increased the odds of low back and neck pain by 4.527 and 4.555, respectively. CONCLUSIONS: This sample had a high frequency of reported MSDs, likely attributed to physiologically strenuous occupational activities repeated on average of 30-40 times daily. Ergonomic interventions, such as the use of handcarts, and occupational training are urgently needed. PMID- 27362733 TI - The relationship between economic conditions and postpartum depression in Taiwan: a nationwide population-based study. AB - BACKGROUND: Understanding mothers' economic conditions and postpartum depression (PPD) is important for determining how they will take care of themselves and their infants during the postnatal period, especially for low-income families. This study examined the relationship between economic conditions and PPD to elucidate the effect of economic contraction on PPD. METHODS: Our population based nationwide study used 2000-2013 the National Health Insurance Research Database of Taiwan. A total of 1240 newly diagnosed PPD patients were recruited. We used the database of the Directorate General of Budget, Accounting, and Statistics of Executive Yuan of Taiwan for national economic indicators. The correlation between economic indicators and PPD was examined. RESULTS: The PPD incidence was positively correlated with yearly unemployment rate, consumer price index, and gross domestic product. During the great recession of 2008-2009, PPD was positively correlated with inflation rate. Consumer price index had a positive correlation with PPD incidence per month when comparing PPD in 2010 with the economic indicators during the great recession. LIMITATIONS: As this retrospective study evaluated macroeconomic indicators, it is unclear whether the macroeconomic indicators' effect on PPD totally reflects the effect of true personal economic status on PPD. CONCLUSIONS: There was a significant association between PPD and economic conditions. This study shows that mothers' familial environment plays an important role in the development of PPD. The impact of the worldwide economic downturn of the great recession on women is persistent. This useful finding may give health policy planners a hint of early discovering and dealing with PPD when worldwide economic downturn. PMID- 27362735 TI - Asymptomatic C-reactive protein elevation in neutropenic children. AB - BACKGROUND: Febrile neutropenia (FN) can be a life-threatening complication in children with malignancies. There is no standardized preventive treatment for childhood FN, and information on C-reactive protein (CRP) elevation in afebrile patients with neutropenia (CEAN) is limited. The aim of this study was therefore to identify the association between CEAN and FN onset, and evaluate the efficacy of broad-spectrum antibiotics for FN prophylaxis. METHODS: We retrospectively reviewed the medical records of 22 consecutive pediatric patients with hematologic malignancies (acute myeloid leukemia, n = 2; acute lymphoid leukemia, n = 20) admitted to the present institution between 2006 and 2011. CEAN was defined as CRP elevation >=0.05 mg/dL between the two most recent blood tests with no fever. We identified CEAN before FN onset, and assessed the efficacy of broad-spectrum antibiotics for FN prevention in CEAN. FN incidence within 48 h after CEAN detection was compared between prophylactic and non-prophylactic episodes. RESULTS: CEAN was observed before FN onset in 20 (55.6%), of 36 FN episodes. Among the 95 analyzed CEAN episodes, broad-spectrum antibiotics had been used for 30 episodes (prophylactic episodes), whereas these antibiotics had not been used in 60 episodes (non-prophylactic episodes). Prophylactic episodes had a significantly lower FN incidence than non-prophylactic episodes (6.7% and 31%, respectively, P < 0.01) within 48 h after CEAN detection. Bacteremia was observed in three non-prophylactic episodes. CONCLUSION: Patients with CEAN are at higher risk of FN, and physicians may consider the use of broad-spectrum antibiotics to prevent FN development. PMID- 27362734 TI - Developmental Outcome and Related Abnormalities in Goats: Comparison Between Somatic Cell Nuclear Transfer- and In Vivo-Derived Concepti During Pregnancy Through Term. AB - Cloning by somatic cell nuclear transfer (SCNT) is characterized by low efficiency and the occurrence of developmental abnormalities, which are rather poorly studied phenomena in goats. This study aimed at comparing overall SCNT efficiency in goats by using in vitro-matured (IVM) or in vivo-matured oocytes and fibroblast donor cells (mock transfected, transgenic, or wild type), also characterizing symptoms of the Abnormal Offspring Syndrome (AOS) in development, comparing results with pregnancies produced by artificial insemination (AI) and in vivo-derived (IVD) embryos. The SCNT group had lower pregnancy rate (18.3%, 11/60), total number of concepti (20.0%, 12/60), term births (3.3%, 2/60), and live births (1.7%, 1/60) than both the IVD (77.8%, 7/9; 155.5%, 14/9; 122.2%, 11/9; 88.8%, 8/9) and the AI (71.4%, 10/14; 121.4%, 17/14; 100%, 14/14; 78.5%, 11/14) groups, respectively (p < 0.05). No SCNT pregnancies reached term using IVM oocytes, but in vivo-matured oocytes resulted in two term transgenic cloned kids. The proportion fetal membrane (FM) weight/birth weight reflected an increase in FM size and cotyledonary enlargement in clones, for disproportionally bigger newborns in relation to cotyledonary numbers. Overall, goat cloning showed losses and abnormality patterns similar to the AOS in cloned cattle and sheep, which have not been previously well recognized in goats. PMID- 27362736 TI - Development of Monte Carlo simulations to provide scanner-specific organ dose coefficients for contemporary CT. AB - The ImPACT (imaging performance assessment of CT scanners) CT patient dosimetry calculator is still used world-wide to estimate organ and effective doses (E) for computed tomography (CT) examinations, although the tool is based on Monte Carlo calculations reflecting practice in the early 1990's. Subsequent developments in CT scanners, definitions of E, anthropomorphic phantoms, computers and radiation transport codes, have all fuelled an urgent need for updated organ dose conversion factors for contemporary CT. A new system for such simulations has been developed and satisfactorily tested. Benchmark comparisons of normalised organ doses presently derived for three old scanners (General Electric 9800, Philips Tomoscan LX and Siemens Somatom DRH) are within 5% of published values. Moreover, calculated normalised values of CT Dose Index for these scanners are in reasonable agreement (within measurement and computational uncertainties of +/ 6% and +/-1%, respectively) with reported standard measurements. Organ dose coefficients calculated for a contemporary CT scanner (Siemens Somatom Sensation 16) demonstrate potential deviations by up to around 30% from the surrogate values presently assumed (through a scanner matching process) when using the ImPACT CT Dosimetry tool for newer scanners. Also, illustrative estimates of E for some typical examinations and a range of anthropomorphic phantoms demonstrate the significant differences (by some 10's of percent) that can arise when changing from the previously adopted stylised mathematical phantom to the voxel phantoms presently recommended by the International Commission on Radiological Protection (ICRP), and when following the 2007 ICRP recommendations (updated from 1990) concerning tissue weighting factors. Further simulations with the validated dosimetry system will provide updated series of dose coefficients for a wide range of contemporary scanners. PMID- 27362737 TI - A Historical Recount: Discovering Meniere's Disease and Its Association With Migraine Headaches. AB - OBJECTIVES: In evaluating the historical context of the first description of Meniere's disease, its association with migraine headaches is compelling. We have outlined the events and observations of Prosper Meniere, which led him to establish a link between migraine headaches and his eponymous disease. STUDY DESIGN: Prosper Meniere's original French writings were translated by our group and used to recount his observations and thoughts. Miles Atkinson's English translations were used as a reference. Additional otological texts of the era were also reviewed as it relates to Meniere's disease. METHODS: Prosper Meniere wrote a series of four articles 1 year before his death. In one of these articles, he makes references to migraine headaches on several occasions. These original writings were analyzed, and the physical findings he described were interpreted based on their relation to migraine headaches. RESULTS: The passages in his published articles provide historical insight into Meniere's observations. His writings describe in detail symptoms of migraine headaches uniquely evident in his patient population. Through his observations, he recognized that in addition to exhibiting symptoms of tinnitus, hearing loss and vertigo his patients also suffered from migraine headaches. CONCLUSIONS: Although his colleagues discounted Meniere's theory concerning migraine headaches, he continued to make deductive inferences and publish his findings, leading to the association of migraine headaches and Meniere's disease. Today, this association continues to be debated, adding to Prosper Meniere's legacy. PMID- 27362738 TI - Content Validity of Temporal Bone Models Printed Via Inexpensive Methods and Materials. AB - HYPOTHESIS: Computed tomographic (CT) scans of the 3-D printed temporal bone models will be within 15% accuracy of the CT scans of the cadaveric temporal bones. BACKGROUND: Previous studies have evaluated the face validity of 3-D printed temporal bone models designed to train otolaryngology residents. The purpose of the study was to determine the content validity of temporal bone models printed using inexpensive printers and materials. METHODS: Four cadaveric temporal bones were randomly selected and clinical temporal bone CT scans were obtained. Models were generated using previously described methods in acrylonitrile butadiene styrene (ABS) plastic using the Makerbot Replicator 2* and Hyrel printers. Models were radiographically scanned using the same protocol as the cadaveric bones. Four images from each cadaveric CT series and four corresponding images from the model CT series were selected, and voxel values were normalized to black or white. Scan slices were compared using PixelDiff software. Gross anatomic structures were evaluated in the model scans by four board certified otolaryngologists on a 4-point scale. RESULTS: Mean pixel difference between the cadaver and model scans was 14.25 +/- 2.30% at the four selected CT slices. Mean cortical bone width difference and mean external auditory canal width difference were 0.58 +/- 0.66 mm and 0.55 +/- 0.46 mm, respectively. Expert raters felt the mastoid air cells were well represented (2.5 +/- 0.5), while middle ear and otic capsule structures were not accurately rendered (all averaged <1.8). CONCLUSION: These results suggest that these models would be sufficient adjuncts to cadaver temporal bones for training residents in cortical mastoidectomies, but less effective for middle ear procedures. PMID- 27362739 TI - Influence of Posterior Fossa Volume on Clinical Outcomes After Vestibular Schwannoma Resection. AB - OBJECTIVES: To determine the influence of posterior fossa dimensions on surgical outcomes after vestibular schwannoma management. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care academic medical center. PATIENTS: Patients with sporadic vestibular schwannomas who underwent surgical resection via retrosigmoid or translabyrinthine techniques. INTERVENTIONS: Diagnostic. MAIN OUTCOME MEASURES: One and two-way analysis of variance (ANOVAs) of the cohort based on volumetric and clinical outcome groupings. RESULTS: A total of 95 patients were identified. A one-way ANOVA looking at the entire cohort of patients showed that outcomes like surgical time (p < 0.001) and whether a Good Outcome (House-Brackmann score of 1 or 2, no complications, and a complete resection) was achieved (p = 0.009) correlated very well with preoperative tumor volume, but not with posterior fossa volume (p = 0.412 and p = 0.345, respectively). However, in medium sized tumors, House-Brackmann group was correlated with posterior fossa volume (p = 0.032). CONCLUSIONS: The present data suggest a small effect of posterior fossa size on some clinical outcomes in medium sized vestibular schwannomas. PMID- 27362740 TI - Acoustic Transmission Characteristics of a Eustachian Tube Volitionally Opened in Two Living Subjects. AB - OBJECTIVE: To assess the acoustic transmission characteristics of the Eustachian tube (ET) in living subjects in verified patent and closed ET states to facilitate the detection and quantification of ET function using acoustic measures such as sonotubometry. PATIENTS: The two subjects in this study had no history of ear disease nor previous ear surgery and were capable of volitionally opening and closing their ET. INTERVENTIONS: Tympanometry and otologic examinations were used to confirm ET patent and closed states by observing tympanic membrane movement with respiration and by acoustic immitance measurements during forced respiration. A series of 500-ms long chirps containing frequencies from 100 Hz to 10 kHz were introduced into the nasal cavity during both ET states and recorded by microphones in both the contralateral naris and external auditory canal. MAIN OUTCOME MEASURES: Acoustic energy transmission through the ET across the 0.1 to 10 kHz frequency range in the closed state versus the patent state. RESULTS: An increase in acoustic energy transmission occurs across the frequencies of 1 to 4 kHz between the closed and patent ET states, particularly in frequencies below 2.5 kHz. CONCLUSIONS: Results support sonotubometry as a potential diagnostic tool for ET dysfunction. Acoustic differences between the ET states manifest as a general increase in transmitted signal amplitude. Characterizing the acoustic properties in the verified patent and closed ET states allows investigators to more reliably interpret sonotubometric tests of ET function. PMID- 27362741 TI - Novel FKBP10 Mutation in a Patient with Osteogenesis Imperfecta Type XI. AB - Osteogenesis imperfecta (OI) is a set of clinically and genetically heterogeneous disorders with autosomal dominant, recessive and X-linked inheritance patterns. The aim of this study was to describe a novel genetic abnormality in a case of OI type XI with mild joint contractures, kyphoscoliosis, muscular atrophy, progressively deforming and multiple bone fractures in a consanguineous Iranian family. Based on the phenotype, investigation of two candidate genes, CRTAP (OI type VII) and FKBP10 (OI type XI) detected a novel homozygous frameshift mutation in the FKBP10 gene. This finding can be useful in accurate genetic counseling and prioritization of molecular analysis of OI in Iranian patients. PMID- 27362742 TI - Chronic fatigue syndrome - an update. AB - BACKGROUND: Chronic fatigue syndrome is a widespread condition with a huge impact not only on a patient's life, but also on society as evidenced by substantial losses of productivity, informal costs, and medical expenses. The high prevalence rates (0.2-6.4%) and the low employment rates (27-41%) are responsible for the enormous burden imposed on society, with loss of productivity representing the highest cost. The objective of this review is to systematically review the recent literature on chronic fatigue syndrome/myalgic encephalomyelitis. METHODS: The published literature between 1 January 1990 and 1 April 2015 was searched using the MEDLINE, Cochrane Library, and Web of Sciences databases. The reference lists of the selected articles were screened for other relevant articles. RESULTS AND CONCLUSIONS: Despite extensive research, none of the proposed etiological factors have shown strong, reproducible scientific evidence. Over the years, the biopsychosocial model integrating many of the proposed hypotheses has been gaining popularity over the biomedical model, where the focus is on one physical cause. Since the etiological mechanism underlying chronic fatigue syndrome is currently unknown, disease-specific treatments do not exist. Various treatments have been investigated but only cognitive behavior therapy (CBT) and graded exercise therapy (GET) have shown moderate effectiveness. PMID- 27362743 TI - Sorption of Highly Hydrophobic Organic Chemicals to Organic Matter Relevant for Fish Bioconcentration Studies. AB - With regard to a potential underestimation of bioconcentration factors (BCF) in flow-through fish tests, sorption of 11 highly hydrophobic organic chemicals (HOCs) (log KOW 5.5-7.8) from different substance classes was systematically investigated for the first time in the presence of fish feed (FF) and filter residues (FR), the organic matter (OM) most relevant for fish bioconcentration studies. Sorption was investigated in batch-equilibrium experiments by solid phase microextraction (SPME) resulting in partitioning coefficients of solid water (Kd), total organic carbon-water (KTOC), and dissolved organic carbon-water (KDOC). Results prove a high affinity of HOCs for FF and FR supporting a significant impact on BCF studies and differing from sorption to Aldrich-humic acid (AHA) utilized as reference sorbent. Sorption is influenced by interactions between HOCs and OM characteristics. For FF, KDOC values were higher than KTOC values. Results help to assess the relevance of interaction of HOCs from different substance classes with OM relevant for BCF studies. PMID- 27362744 TI - Synthesis and characterization of mixed ligand chiral nanoclusters. AB - Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. PMID- 27362746 TI - Synthesis of 2,4,6-Trisubstituted Pyridines by Oxidative Eosin Y Photoredox Catalysis. AB - Eosin Y, an organic dye, was activated as a photoredox catalyst in the presence of molecular oxygen using visible light and, when it was used in the reaction of aryl ketones and benzyl amines, afforded good yields (52-87%) of 2,4,6 triarylpyridines (21 examples) at ambient temperature. The aryl groups at the 2- and 6-positions are derived from ketones, while benzyl amine plays the dual role of providing an aryl functionality at the 4-position of pyridine as well as being a nitrogen donor. PMID- 27362745 TI - Conformational Dynamics and the Binding of Specific and Nonspecific DNA by the Autoinhibited Transcription Factor Ets-1. AB - The affinity of the Ets-1 transcription factor for DNA is autoinhibited by an intrinsically disordered serine-rich region (SRR) and a helical inhibitory module (IM) appended to its winged helix-turn-helix ETS domain. Using NMR spectroscopy, we investigated how Ets-1 recognizes specific versus nonspecific DNA, with a focus on the roles of protein dynamics and autoinhibition in these processes. Upon binding either DNA, the two marginally stable N-terminal helices of the IM predominantly unfold, but still sample partially ordered conformations. Also, on the basis of amide chemical shift perturbation mapping, Ets-1 associates with both specific and nonspecific DNA through the same canonical ETS domain interface. These interactions are structurally independent of the SRR, and thus autoinhibition does not impart DNA-binding specificity. However, relative to the pronounced NMR spectroscopic changes in Ets-1 resulting from specific DNA binding, the spectra of the nonspecific DNA complexes showed conformational exchange broadening and lacked several diagnostic amide and indole signals attributable to hydrogen bonding interactions seen in reported X-ray crystallographic structures of this transcription factor with its cognate DNA sequences. Such differences are highlighted by the chemical shift and relaxation properties of several interfacial lysine and arginine side chains. Collectively, these data support a general model in which Ets-1 interacts with nonspecific DNA via dynamic electrostatic interactions, whereas hydrogen bonding drives the formation of well-ordered complexes with specific DNA. PMID- 27362747 TI - The predictive value of Von Willebrand factor antigen plasma levels in children with acute lung injury. AB - OBJECTIVE: Von Willebrand factor antigen (VWF-Ag) is proved to be a marker for pulmonary endothelial injury in acute lung injury (ALI). We aimed to evaluate the predictive value of VWF-Ag plasma levels in children with ALI. METHODS: Prospective controlled study included 40 children with ALI as a patient group, 40 healthy children as a control group. Plasma VWF Ag level was measured at days 1 and 3 in patient group and measured once for control group. RESULTS: The commonest cause of ALI was pneumonia (35%). VWF Ag plasma levels were significantly higher in patient group than control group at days 1 and 3 (P = 0.001 and 0.002), respectively. Mean PaO2 /FiO2 of patients with ALI was 137 +/- 65.38. Mortality was 30%. The deceased subgroup had significantly higher plasma levels of VWF Ag at days 1 and 3 than survived subgroup (P = 0.016 and P < 0.0001, respectively), significantly higher C reactive protein (P = 0.001), significantly higher rate of multisystem organ failure (MSOF) (P = 0.001), shorter duration of pediatric intensive care unit (PICU), and mechanical ventilation (MV) free days (P < 0.0001). Elevated VWF at day 1 was associated with significant MSOF (P = 0.011) and mortality (P = 0.009), while elevated VWF Ag at day 3 was associated with significant increase in MSOF (P = 0.004), length of MV (P = 0.024), and PICU stay (P = 0.011). VWF Ag has a high sensitivity (94.2%, 93.4%) and specificity (83.1%, 81.7%) for prediction of mortality at days 1 and 3, respectively. Multivariate regression analysis revealed that plasma VWF Ag level is an independent predictor of mortality in ARDS pediatric patients. CONCLUSION: Plasma VWF Ag level is an excellent predictive marker for outcome in children with ALI/ARDS. Pediatr Pulmonol. 2017;52:91-97. (c) 2016 Wiley Periodicals, Inc. PMID- 27362748 TI - Triethylenetetramine-N,N,N',N'',N''',N'''-hexaacetic Acid (TTHA) and TTHA Bis(butanamide) as Chelating Agents Relevant to Radiopharmaceutical Applications. PMID- 27362749 TI - Nonsurgical Management of Neuroendocrine Cancer of the Cervix: Brief Report. AB - OBJECTIVES: The aim of this study was to evaluate disease progression and overall survival in patients diagnosed with neuroendocrine carcinoma of the cervix treated with chemotherapy and radiation without surgical intervention; we hypothesize similar overall survival to the surgical intervened cases. METHODS: This study used a retrospective analysis of patients with neuroendocrine carcinoma of the cervix who were not surgically managed. Review was performed from 1990 to 2014. The data collected included demographics, stage of disease, and outcomes after each treatment. Specific chemotherapy regimen given and radiation dosage were reviewed. Overall survival and recurrence rates were calculated. RESULTS: A total of 16 patients met inclusion criteria. Six patients were diagnosed with stage I; these patients had 83.3% 2-year overall survival, 83.3% 5-year overall survival, and a recurrence rate of 16.6%. Three patients were diagnosed with stage II; these patients had 66.6% 2-year overall survival, 0% 5-year overall survival, and a recurrence rate of 100%. Seven patients were diagnosed with stage IV; these patients had 14.3% 2-year overall survival and 0% 5-year overall survival and never underwent remission. CONCLUSIONS: Our findings noted a comparable overall survival with lower rates of recurrence in patients with early-stage disease using chemotherapy and radiation therapy alone as primary means of treatment. Nonsurgical management of neuroendocrine carcinoma of the cervix may be of benefit in early-stage disease. PMID- 27362750 TI - New Insights into Human 17beta-Hydroxysteroid Dehydrogenase Type 14: First Crystal Structures in Complex with a Steroidal Ligand and with a Potent Nonsteroidal Inhibitor. AB - 17beta-HSD14 is a SDR enzyme able to oxidize estradiol and 5-androstenediol using NAD(+). We determined the crystal structure of this human enzyme as the holo form and as ternary complexes with estrone and with the first potent, nonsteroidal inhibitor. The structures reveal a conical, rather large and lipophilic binding site and are the starting point for structure-based inhibitor design. The two natural variants (S205 and T205) were characterized and adopt a similar structure. PMID- 27362751 TI - Parents' Attitudes to Risk and Injury to Children and Young People on Farms. AB - OBJECTIVES: Children and young people growing up in a farm environment run a greater risk of being injured or dying in an accident than their non-farming counterparts. This study examines farming parents' attitudes and experiences of having their children grow up on farms, one of the most dangerous work environments as their home, everyday environment and playground. METHOD: Data were collected using two ethnological methods, a question list and interviews, with a study population of 20 parents. The data were analysed phenomenologically. RESULTS: The analysis pursued four themes: i) the most dangerous places and situations on the farm; ii) children's tasks on the farm; iii) children as a safety risk on the farm; and iv) farm risk education for children. CONCLUSIONS: Most parents know the risks on their farm, but are sometimes careless when working under stress or exhaustion. Some parents wanted more information and some wanted compulsory preventative or safety measures by manufacturers, e.g. a safety belt as standard on the extra seat in tractors. Children's friends were described as one of the greatest risks for injury due to peer pressure. Some parents mentioned that people who grow up on farms are sometimes 'blind' to the dangers. Other parents seemed to overlook the risks and had their children carrying out tasks for which they were not mentally or physically equipped. Some of the tasks the children reportedly carried out on farms contravened Swedish legislation. It is thus important for farming parents to be repeatedly reminded of the risks to their children and to increase their awareness of how to prevent and eliminate risks in order to avoid accidents on the farm. The situation for farm children is highlighted in a critical discussion. PMID- 27362752 TI - Novel Methods for Surface EMG Analysis and Exploration Based on Multi-Modal Gaussian Mixture Models. AB - This paper introduces a new method for data analysis of animal muscle activation during locomotion. It is based on fitting Gaussian mixture models (GMMs) to surface EMG data (sEMG). This approach enables researchers/users to isolate parts of the overall muscle activation within locomotion EMG data. Furthermore, it provides new opportunities for analysis and exploration of sEMG data by using the resulting Gaussian modes as atomic building blocks for a hierarchical clustering. In our experiments, composite peak models representing the general activation pattern per sensor location (one sensor on the long back muscle, three sensors on the gluteus muscle on each body side) were identified per individual for all 14 horses during walk and trot in the present study. Hereby we show the applicability of the method to identify composite peak models, which describe activation of different muscles throughout cycles of locomotion. PMID- 27362753 TI - A Generalized Coherence Framework for Detecting and Characterizing Nonlinear Interactions in the Nervous System. AB - OBJECTIVE: This paper introduces a generalized coherence framework for detecting and characterizing nonlinear interactions in the nervous system, namely cross spectral coherence (CSC). CSC can detect different types of nonlinear interactions including harmonic and intermodulation coupling as present in static nonlinearities and also subharmonic coupling, which only occurs with dynamic nonlinearities. METHODS: We verified the performance of CSC in model simulations with both static and dynamic nonlinear systems. We applied CSC to investigate nonlinear stimulus-response interactions in the human proprioceptive system. A periodic movement perturbation was imposed to the wrist when the subjects performed an isotonic wrist flexion. CSC analysis was performed between the perturbation and brain responses (electroencephalogram, EEG). RESULTS: Both the simulation and the application demonstrated that CSC successfully detected different types of nonlinear interactions. High-order nonlinearities were revealed in the proprioceptive system, shown in harmonic and intermodulation coupling between the perturbation and EEG for all subjects. Subharmonic coupling was found in some subjects but not all. CONCLUSION: This paper provides a general tool to detect and characterize nonlinear nature and dynamics of the nervous system. The application of CSC on the experimental dataset indicates a complex nonlinear dynamics in the proprioceptive system. SIGNIFICANCE: This novel framework 1) unveils the nonlinear neural dynamics in a more complete way than the existing coherence measures, and 2) is more suitable for estimating the input output relation regarding both phase and amplitude compared to phase synchrony measures (which only consider phase coupling). Subharmonic coupling is reported in human proprioceptive system for the first time. PMID- 27362754 TI - Simultaneous Monitoring of Ballistocardiogram and Photoplethysmogram Using a Camera. AB - We present a noncontact method to measure ballistocardiogram (BCG) and photoplethysmogram (PPG) simultaneously using a single camera. The method tracks the motion of facial features to determine displacement BCG, and extracts the corresponding velocity and acceleration BCGs by taking first and second temporal derivatives from the displacement BCG, respectively. The measured BCG waveforms are consistent with those reported in the literature and also with those recorded with an accelerometer-based reference method. The method also tracks PPG based on the reflected light from the same facial region, which makes it possible to track both BCG and PPG with the same optics. We verify the robustness and reproducibility of the noncontact method with a small pilot study with 23 subjects. The presented method is the first demonstration of simultaneous BCG and PPG monitoring without wearing any extra equipment or marker by the subject. PMID- 27362755 TI - Radiotherapy Planning Using an Improved Search Strategy in Particle Swarm Optimization. AB - OBJECTIVE: Evolutionary stochastic global optimization algorithms are widely used in large-scale, nonconvex problems. However, enhancing the search efficiency and repeatability of these techniques often requires well-customized approaches. This study investigates one such approach. METHODS: We use particle swarm optimization (PSO) algorithm to solve a 4D radiation therapy (RT) inverse planning problem, where the key idea is to use respiratory motion as an additional degree of freedom in lung cancer RT. The primary goal is to administer a lethal dose to the tumor target while sparing surrounding healthy tissue. Our optimization iteratively adjusts radiation fluence-weights for all beam apertures across all respiratory phases. We implement three PSO-based approaches: conventionally used unconstrained, hard-constrained, and our proposed virtual search. As proof of concept, five lung cancer patient cases are optimized over ten runs using each PSO approach. For comparison, a dynamically penalized likelihood (DPL) algorithm a popular RT optimization technique is also implemented and used. RESULTS: The proposed technique significantly improves the robustness to random initialization while requiring fewer iteration cycles to converge across all cases. DPL manages to find the global optimum in 2 out of 5 RT cases over significantly more iterations. CONCLUSION: The proposed virtual search approach boosts the swarm search efficiency, and consequently, improves the optimization convergence rate and robustness for PSO. SIGNIFICANCE: RT planning is a large-scale, nonconvex optimization problem, where finding optimal solutions in a clinically practical time is critical. Our proposed approach can potentially improve the optimization efficiency in similar time-sensitive problems. PMID- 27362756 TI - Localizing Microaneurysms in Fundus Images Through Singular Spectrum Analysis. AB - GOAL: Reliable recognition of microaneurysms (MAs) is an essential task when developing an automated analysis system for diabetic retinopathy (DR) detection. In this study, we propose an integrated approach for automated MA detection with high accuracy. METHODS: Candidate objects are first located by applying a dark object filtering process. Their cross-section profiles along multiple directions are processed through singular spectrum analysis. The correlation coefficient between each processed profile and a typical MA profile is measured and used as a scale factor to adjust the shape of the candidate profile. This is to increase the difference in their profiles between true MAs and other non-MA candidates. A set of statistical features of those profiles is then extracted for a K-nearest neighbor classifier. RESULTS: Experiments show that by applying this process, MAs can be separated well from the retinal background, the most common interfering objects and artifacts. CONCLUSION: The results have demonstrated the robustness of the approach when testing on large scale datasets with clinically acceptable sensitivity and specificity. SIGNIFICANCE: The approach proposed in the evaluated system has great potential when used in an automated DR screening tool or for large scale eye epidemiology studies. PMID- 27362757 TI - Development of an Open-Source, Discrete Element Knee Model. AB - OBJECTIVE: Biomechanical modeling is an important tool in that it can provide estimates of forces that cannot easily be measured (e.g., soft tissue loads). The goal of this study was to develop a discrete element model of the knee that is open source to allow for utilization of modeling by a wider audience of researchers. METHODS: A six degree-of-freedom tibiofemoral and one degree-of freedom patellofemoral joint were created in OpenSim. Eighteen ligament bundles and tibiofemoral contact were included in the model. RESULTS: During a passive flexion movement, maximum deviation of the model from the literature occurred at the most flexed angle with deviations of 2 degrees adduction, 7 degrees internal rotation, 1-mm posterior translation, 12-mm inferior translation, and 4 mm lateral translation. Similarly, the overall elongation of the ligaments agreed with literature values with strains of less than 13%. CONCLUSION: These results provide validation of the physiological relevance of the model. SIGNIFICANCE: This model is one of the few open source, discrete element knee models to date, and has many potential applications, one being for use in an open-source cosimulation framework. PMID- 27362758 TI - SVM-Based System for Prediction of Epileptic Seizures From iEEG Signal. AB - OBJECTIVE: This paper describes a data-analytic modeling approach for the prediction of epileptic seizures from intracranial electroencephalogram (iEEG) recording of brain activity. Even though it is widely accepted that statistical characteristics of iEEG signal change prior to seizures, robust seizure prediction remains a challenging problem due to subject-specific nature of data analytic modeling. METHODS: Our work emphasizes the understanding of clinical considerations important for iEEG-based seizure prediction, and proper translation of these clinical considerations into data-analytic modeling assumptions. Several design choices during preprocessing and postprocessing are considered and investigated for their effect on seizure prediction accuracy. RESULTS: Our empirical results show that the proposed support vector machine based seizure prediction system can achieve robust prediction of preictal and interictal iEEG segments from dogs with epilepsy. The sensitivity is about 90 100%, and the false-positive rate is about 0-0.3 times per day. The results also suggest that good prediction is subject specific (dog or human), in agreement with earlier studies. CONCLUSION: Good prediction performance is possible only if the training data contain sufficiently many seizure episodes, i.e., at least 5-7 seizures. SIGNIFICANCE: The proposed system uses subject-specific modeling and unbalanced training data. This system also utilizes three different time scales during training and testing stages. PMID- 27362759 TI - A New Flea Species of the Genus Cleopsylla (Siphonaptera: Stephanocircidae) from Northwestern Argentina. AB - A new species of flea of the genus Cleopsylla Rothschild, 1914 (Siphonaptera: Stephanocircidae) is described from sigmodontine rodents from northwestern Argentina. In Argentina, the genus was cited for the first time in 2008, but the species was erroneously identified. An identification key to species of Cleopsylla is presented. PMID- 27362760 TI - Systematic Review and Meta-Analysis on the Role of Chemotherapy in Advanced and Metastatic Neuroendocrine Tumor (NET). AB - BACKGROUND/OBJECTIVES: In the era of somatostatin analogues and targeted therapies, the role of chemotherapy in NET remains largely undefined. This systematic review aimed to assess the effect of chemotherapy on response rates (RR), progression-free survival (PFS), overall survival (OS) and toxicity compared to other chemotherapies/systemic therapies or best supportive care in patients with advanced or metastatic NET. METHODS: Randomised controlled trials (RCTs) from 1946 to 2015 were identified from MEDLINE, EMBASE, other databases and conference proceedings. Review of abstracts, quality assessment and data abstraction were performed independently by two investigators. Meta-analyses were conducted using Mantel-Haenszel analysis with random-effects modelling. RESULTS: Six RCTs comparing standard streptozotocin plus 5-fluorouacil (STZ/5FU) chemotherapy to other chemotherapy regimens, and 2 comparing this to interferon (IFN) were included. Only 1 study was considered at low risk of bias. STZ/5-FU was no different to other chemotherapies in response rate [RR 0.96; 95% confidence interval (CI) 0.72-1.27], PFS (RR 0.95; CI 0.81-1.13), or OS (RR 1.03; CI 0.77-1.39). IFN may produce higher response than STZ/5FU (RR 0.20; CI 0.04 1.13), but event rates were small and survival was no different. Interferon was associated with higher overall haematological (RR 0.47; CI 0.27-0.82) and lower overall renal toxicity (RR 3.61; CI 1.24-10.51). CONCLUSION: Strong evidence is lacking in the area of chemotherapy in neuroendocrine tumors. There is currently no evidence that one chemotherapeutic regimen is significantly better than the other, nor is interferon better than chemotherapy. There is an urgent need to design RCTs comparing modern chemotherapy to other agents in NET. PMID- 27362762 TI - Information Extraction of High Resolution Remote Sensing Images Based on the Calculation of Optimal Segmentation Parameters. AB - Multi-scale image segmentation and the selection of optimal segmentation parameters are the key processes in the object-oriented information extraction of high-resolution remote sensing images. The accuracy of remote sensing special subject information depends on this extraction. On the basis of WorldView-2 high resolution data, the optimal segmentation parameters methodof object-oriented image segmentation and high-resolution image information extraction, the following processes were conducted in this study. Firstly, the best combination of the bands and weights was determined for the information extraction of high resolution remote sensing image. An improved weighted mean-variance method was proposed andused to calculatethe optimal segmentation scale. Thereafter, the best shape factor parameter and compact factor parameters were computed with the use of the control variables and the combination of the heterogeneity and homogeneity indexes. Different types of image segmentation parameters were obtained according to the surface features. The high-resolution remote sensing images were multi scale segmented with the optimal segmentation parameters. Ahierarchical network structure was established by setting the information extraction rules to achieve object-oriented information extraction. This study presents an effective and practical method that can explain expert input judgment by reproducible quantitative measurements. Furthermore the results of this procedure may be incorporated into a classification scheme. PMID- 27362761 TI - Galleria mellonella as a model host for microbiological and toxin research. AB - Mammals are widely used by microbiologists as a model host species to study infectious diseases of humans and domesticated livestock. These studies have been pivotal for our understanding of mechanisms of virulence and have allowed the development of diagnostics, pre-treatments and therapies for disease. However, over the past decade we have seen efforts to identify organisms which can be used as alternatives to mammals for these studies. The drivers for this are complex and multifactorial and include cost, ethical and scientific considerations. Galleria mellonella have been used as an alternative infection model since the 1980s and its utility for the study of bacterial disease and antimicrobial discovery was recently comprehensively reviewed. The wider applications of G. mellonella as a model host, including its susceptibility to 29 species of fungi, 7 viruses, 1 species of parasite and 16 biological toxins, are described in this perspective. In addition, the latest developments in the standardisation of G. mellonella larvae for research purposes has been reviewed. PMID- 27362763 TI - Alterations of Diffusion Kurtosis and Neurite Density Measures in Deep Grey Matter and White Matter in Parkinson's Disease. AB - In Parkinson's disease (PD), pathological microstructural changes occur and such changes might be detected using diffusion magnetic resonance imaging (dMRI). However, it is unclear whether dMRI improves PD diagnosis or helps differentiating between phenotypes, such as postural instability gait difficulty (PIGD) and tremor dominant (TD) PD. We included 105 patients with PD and 44 healthy controls (HC), all of whom underwent dMRI as part of the prospective Swedish BioFINDER study. Diffusion kurtosis imaging (DKI) and neurite density imaging (NDI) analyses were performed using regions of interest in the basal ganglia, the thalamus, the pons and the midbrain as well as tractography of selected white matter tracts. In the putamen, the PD group showed increased mean diffusivity (MD) (p = .003), decreased fractional anisotropy (FA) (p = .001) and decreased mean kurtosis (MK), compared to HC (p = .024). High MD and a low MK in the putamen were associated with more severe motor and cognitive symptomatology (p < .05). Also, patients with PIGD exhibited increased MD in the putamen compared to the TD patients (p = .009). In the thalamus, MD was increased (p = .001) and FA was decreased (p = .032) in PD compared to HC. Increased MD and decreased FA correlated negatively with motor speed and balance (p < .05). In the superior longitudinal fasciculus (SLF), MD (p = .019) and fiso were increased in PD compared to HC (p = .03). These changes correlated negatively with motor speed (p < .002) and balance (p < .037). However, most of the observed changes in PD were also present in cases with either multiple system atrophy (n = 11) or progressive supranuclear palsy (n = 10). In conclusion, PD patients exhibit microstructural changes in the putamen, the thalamus, and the SLF, which are associated with worse disease severity. However, the dMRI changes are not sufficiently specific to improve the diagnostic work-up of PD. Longitudinal studies should evaluate whether dMRI measures can be used to track disease progression. PMID- 27362764 TI - Beyond Wishful Thinking: Integrating Consumer Preferences in the Assessment of Dietary Recommendations. AB - Convenience, taste, and prices are the main determinants of food choices. Complying with dietary recommendations therefore imposes a "taste cost" on consumers, potentially hindering adoption of those recommendations. The study presents and applies a new methodology, based on economic theory, to quantify this taste cost and assess the health and welfare effects of different dietary recommendations. Then, by comparison of those effects, we identify socially desirable recommendations that are most compatible with consumer preferences (i.e., that best balance health benefits against"taste cost") and should be prioritized for promotion. The methodology proceeds in three-steps: first, an economic-behavioral model simulates how whole diets would change if consumers complied with dietary recommendations; second, an epidemiological model estimates the number of deaths avoided (DA) due to the dietary change; third, an efficiency analysis weighs the health benefits against the taste and policy costs of each recommendation. The empirical model is calibrated using French data. We find that recommendations to reduce consumption of red meat and soft-drinks, or raise consumption of milk products and fish/seafood impose relatively moderate taste costs. By comparison, recommendations related to F&V consumption and, to a lesser extent, butter/cream/cheese, snacks, and all meats impose larger taste costs on consumers. The F&V recommendation is the costliest for consumers to comply with, but it also reduces diet-related mortality the most, so that a large budget could be allocated to promoting F&V consumption while keeping this policy cost beneficial. We conclude that promotion of most dietary recommendations improves social welfare. Our framework complements the programming models available in nutrition and public health: those models are best used to identify dietary targets, following which our framework identifies cost-beneficial ways of moving towards those targets. PMID- 27362766 TI - Reducing Antimicrobial Usage in Pig Production without Jeopardizing Production Parameters. AB - Antimicrobial usage (AMU) has been described to be high in pig production. Although farmers are aware of the high usage, little is known about intervention to improve the situation. This study evaluated the extent to which AMU could be reduced in pig production by the optimization of herd management, biosecurity status, vaccination strategy, anthelmintic therapy and advice on prudent AMU. Furthermore, the effects of these interventions on the herd production results were explored. This intervention study was conducted on 61 Flemish pig herds and included three visits per herd. During the initial visit, information was gathered on herd management, biosecurity status (quantified by means of the Biocheck.UGentTM risk-based scoring system), vaccination strategy, anthelmintic therapy and AMU. This info was then translated into a herd-specific action plan which was discussed with the farmer and herd veterinarian/other advisors during the second visit. In the final herd visit (+/-8 months later), comparable data were obtained to evaluate the progress. Overall, a significant improvement of 2.4 points external and 7 points internal biosecurity on the herds was obtained, combined with additional vaccination, anthelmintic therapy and prudent AMU. This was accompanied by a significant reduction in the AMU with a decrease of 52% for the pigs from birth till slaughter and 32% for breeding animals, based on treatment incidences (TIs) and included an important reduction in the use of critically important antimicrobials. More importantly, the increased biosecurity levels and decreased AMU were combined with significantly improved technical results such as the number of weaned piglets per sow per year (+1.1), daily weight gain (+5.9 g/day) and mortality in the finisher period (-0.6%). Guided interventions as a team effort of farmer and herd veterinarian/other advisors have shown to be a promising method in the reduction of AMU in pig production. PMID- 27362765 TI - Predictors of Hospitalized Exacerbations and Mortality in Chronic Obstructive Pulmonary Disease. AB - BACKGROUND AND AIM: Exacerbations of chronic obstructive pulmonary disease (COPD) carry significant consequences for patients and are responsible for considerable health-care costs-particularly if hospitalization is required. Despite the importance of hospitalized exacerbations, relatively little is known about their determinants. This study aimed to analyze predictors of hospitalized exacerbations and mortality in COPD patients. METHODS: This was a retrospective population-based cohort study. We selected 900 patients with confirmed COPD aged >=35 years by simple random sampling among all COPD patients in Cantabria (northern Spain) on December 31, 2011. We defined moderate exacerbations as events that led a care provider to prescribe antibiotics or corticosteroids and severe exacerbations as exacerbations requiring hospital admission. We observed exacerbation frequency over the previous year (2011) and following year (2012). We categorized patients according to COPD severity based on forced expiratory volume in 1 second (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 1-4). We estimated the odds ratios (ORs) by logistic regression, adjusting for age, sex, smoking status, COPD severity, and frequent exacerbator phenotype the previous year. RESULTS: Of the patients, 16.4% had >=1 severe exacerbations, varying from 9.3% in mild GOLD grade 1 to 44% in very severe COPD patients. A history of at least two prior severe exacerbations was positively associated with new severe exacerbations (adjusted OR, 6.73; 95% confidence interval [CI], 3.53 12.83) and mortality (adjusted OR, 7.63; 95%CI, 3.41-17.05). Older age and several comorbidities, such as heart failure and diabetes, were similarly associated. CONCLUSIONS: Hospitalized exacerbations occurred with all grades of airflow limitation. A history of severe exacerbations was associated with new hospitalized exacerbations and mortality. PMID- 27362768 TI - Molecular targets of metformin antitumor action. AB - Epidemiological studies have shown that metformin, a first line therapeutic agent for diabetes mellitus, reduced the risk of developing various malignancies. Several preclinical studies established some possible mechanisms of its anticancer effects. The primary effect of metformin action is a decrease in cell energy status, which activates AMP-activated kinase (AMPK), a cellular metabolic sensor. This event is followed by a decrease in serum concentrations of insulin and insulin growth factor I (IGF-I), the potent mitogens for cancer cells. In addition to the indirect mode of action, metformin may exhibit direct inhibitory effect on cancer cells by targeting mammalian target of rapamycin (mTOR) signaling and anabolic processes. This review gathers information on mechanisms of metformin antitumor activity, with special attention given to the impact of this antidiabetic drug on insulin/PI3K/mTOR and AMPK signaling. Furthermore, the factors required for this novel activity of metformin are discussed. PMID- 27362767 TI - Paradoxical Reductions in Serum Anti-p53 Autoantibody Levels by Chemotherapy in Unresectable Colorectal Cancer: An Observational Study. AB - OBJECTIVE: The anti-p53 autoantibody is an emerging tumor marker that is commonly produced in response to p53 mutations. The usefulness of this antibody has been suggested in screening for and the monitoring of recurrence in colorectal cancer; however, its significance as a marker during chemotherapy remains largely unknown. METHODS: We measured serum anti-p53 antibody levels in patients with unresectable colorectal cancer who underwent first-line systemic chemotherapy. Tumor responses were evaluated by computed tomography. We determined whether temporal changes in this antibody during therapy are associated with radiological responses. RESULTS: Of the 83 patients in our study, 29 (35%) had elevated serum anti-p53 antibody levels before chemotherapy. Among these, antibody levels decreased in all 14 responders. In contrast, among those patients with elevated pretherapeutic serum anti-p53 antibody levels, 89% showed a paradoxical decrease in antibody levels and exhibited disease progression after chemotherapy. Moreover, serum anti-p53 antibody levels before and after chemotherapy were not associated with survival. CONCLUSION: These results suggest that serum anti-p53 antibody levels are of limited value in the evaluation of responses to palliative chemotherapy in patients with colorectal cancer. PMID- 27362769 TI - Effects of chronic l-DOPA administration on neurogenic and endothelium-dependent relaxation responses in rabbit corpus cavernosum. AB - BACKGROUND: Dopamine is a crucial central neurotransmitter that plays a fundamental role in the autonomic and somatic components of penile reflexes in animals and humans. Similar to the erectile responses of dopamine, systemic administration of l-DOPA induces yawning and penile erection in some species. The possible effects of l-DOPA on nitric oxide (NO)-dependent and -independent non adrenergic non-cholinergic (NANC) relaxation responses mediated by electrical field stimulation (EFS) and endothelium-dependent relaxation were investigated in this study. METHODS: Thirty-two adult albino male rabbits, in two- and four-week treatment groups, were divided into three subgroups: control group (saline injected) (n=4), 3mg/kg/day (low dose) l-DOPA-injected groups (n=6) and 12mg/kg/day (high dose) l-DOPA-injected groups (n=6). After the intraperitoneal injection treatments, the corpus cavernosum tissues were placed in organ bath chambers. The EFS-mediated responses, and the concentration-response curve to carbachol, sodium nitroprusside (SNP), sildenafil were assessed. RESULTS: The two week treatment with high-dose l-DOPA decreased the NO-dependent NANC relaxation responses, while there was no change in the low-dose two- and four-week treatment groups. The NO-independent NANC relaxation responses in the two-week groups decreased, and the responses in the four-week groups were unchanged when compared to the controls. The relaxation responses to carbachol showed no differences among all groups except for the high-dose four-week l-DOPA group. The relaxation responses of SNP and sildenafil were increased in all of the treatment groups when compared to the controls. CONCLUSIONS: The observed increases in SNP- and sildenafil-induced responses, along with the decreased EFS-mediated responses, suggest increased sensitivity in the NO-signalling pathway following l-DOPA administration. PMID- 27362770 TI - Involvement of CGRP receptors in retinal spreading depression. AB - BACKGROUND: Cortical spreading depression (CSD) is a transient propagating excitation of synaptic activity followed by depression, which is implicated in migraine with aura and is regarded as the underlying cause of migraine. Calcitonin-gene related peptide (CGRP) receptors play a crucial role in mediating the magnitude of CSD in rat cortical slice. This study aimed to examine whether CGRP receptors are involved in retinal spreading depression (RSD) in chicks. METHODS: Western blot was used for detection of calcitonin-receptor like receptor (CALCRL) and intrinsic optical imaging was used for pharmacological investigation. RESULTS: We found that the key component of CGRP receptor, CALCRL, is expressed in the chick retina. Using an in vitro migraine RSD model, we demonstrated that BIBN4096, a potent antagonist for CGRP receptors, markedly reduced the magnitude of RSD induced by K(+), but also the propagation rate. CONCLUSIONS: The data suggest that CGRP receptors mediate RSD propagation involving neuronal mechanism and approve that RSD is an efficient in vitro approach for assessing anti-migraine drugs targeting CGRP receptors. PMID- 27362771 TI - Resolvin D1 down-regulates CYP1A1 and PTGS2 gene in the HUVEC cells treated with benzo(a)pyrene. AB - BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) can interact with lipids and their derivatives and have been known to induce atherosclerosis. The aim of this study was to evaluate the impact of Resolvin D1 (RvD1) on inflammatory-state realted proteins and genes in the human primary umbilical vein endothelial HUVEC cells exposed to benzo(a)pyrene (BaP). METHODS: We analyzed the influence of RvD1 and/or BaP on cyclooxygenase-2 (COX-2), cytosolic prostaglandine E2 synthase (cPGES), glutathione S transferase (GSTM1) and aryl hydrocarbon receptor (AhR) protein expression by Western blot. Additionaly, phospholipase A2 (cPLA2) and cytochrome P450 (CYP1A1) activity, as well as AhR, CYP1A1, phospholipase A2 (PLA2G4A) and prostaglandin synthase 2 (PTGS2) gene expression by qRT-PCR was studied. RESULTS: RvD1 down-regulates cytochrome P450 (CYP1A1) and prostaglandin synthase 2 (PTGS2) gene expression in HUVEC cells exposed to BaP. Repressesion of COX-2, cPGES and overexpressesion of GSTM1 protein was noted after co-treatment with RvD1 and BaP. After incubation with RvD1 an increase of cPLA2 and a decrease of CYP1A1 activity was observed when compared to BaP treated alone endothelial cells. CONCLUSIONS: Our data suggests that RvD1 can significantly contributes on vascular function and alleviates the harmful effects caused by BaP, which might potentially aid in the repair of the injured endothelium. PMID- 27362773 TI - School Day Energy Expenditure in Elementary School Children. AB - BACKGROUND: The purpose was to characterize energy expenditure (EE) during academic subjects and activities during an elementary school day. METHODS: Children in 2nd to 4th grades (N = 33) wore the SenseWear Armband (SWA) for 5 school days to measure EE. Teachers' logs were compared with SWA data to extract information about EE throughout the day. Energy expenditure was also compared among grades. RESULTS: After controlling for body mass, grade level was not a significant predictor of average daily caloric expenditure, F (2, 17.58) = .29, P = .75, omega(2) = .05. When comparing activities throughout the day, relative rates of EE differed significantly, Wilks' F (7, 23) = 52.2, P = .00, etap(2) = .94, with PE and recess having higher EE. When academic subjects were compared (math, science, language arts), relative rate of EE was also significantly different, Wilks' F (2, 30) = 4.31, P = .02, etap(2) = .22. For the full sample, relative rate EE was higher in science than in language arts. CONCLUSIONS: The school day provides opportunity for EE for children. These data support the potential benefit of active instruction in language arts as a method to increase school day EE. PMID- 27362774 TI - Evolutionary Diversity of Suid Herpesvirus 1 Based on Ul44 Partial Sequences. AB - OBJECTIVE: The aim of this study was to use partial Ul44 sequences (glycoprotein C) of Suid herpesvirus 1 to examine the evolution and dynamics of the virus in different periods and hosts. METHODS: Phylogenetic trees were constructed using the software MrBayes after analysis in the software jModelTest to evaluate the best phylogenetic models. The software SplitsTree 4.0 was used to create phylogenetic networks, and the BEAST program was used to generate data on phylogeography. Replication kinetics and serum neutralization tests were applied to tree strains from different phylogenetic groups. RESULTS: Ul44 sequences derived from domestic swine and wild swine clustered in different clades and had different selective pressures depending on the host. We found no differences in replication kinetics and serum neutralization tests in the strains tested. Data show that the evolution of herpesviruses is complex, and different genetic groups may be evolving at different rates. Ul44 is an important marker for molecular evolution and epidemiology studies, but it is not useful for biological information. PMID- 27362775 TI - Microwave ablation-assisted liver gene transfection in rats. AB - PURPOSE: Thermal ablation has been used to manage liver malignancy. This study aimed to assess histological changes in rat liver after microwave ablation (MWA) and to investigate whether thermal damage caused by MWA on surrounding liver tissue enhances the efficiency of liver gene transfer. METHODS: MWA was applied to rat liver, and the pathological tissue and ultrastructural changes were evaluated. Green fluorescent protein (GFP) and Renilla luciferase-expressing plasmids were administered to liver tissues by direct injection. GFP expression in liver tissue was analysed in frozen sections using an inverted fluorescence microscope, and Renilla luciferase expression in target tissue was determined using a luminometer. RESULTS: Tissue demarcations were observed in liver tissue after ablation, and a transition zone with morphological changes was present between necrotic and normal tissue. Hepatocytes in the transition zone showed decreased numbers of microvilli on cell surfaces and increased extracellular space. GFP expression was observed in the transition zone after MWA and plasmid injection and lasted up to 7 days post-ablation. Both the fluorescence and luminescence levels in the transition zone of the liver tissue were significantly higher than those in the untreated tissue (P < 0.001). CONCLUSIONS: Direct plasmid injection to the liver tissue of the transition zone after MWA can achieve effective gene transfection. These findings provide an experimental basis for exploring MWA-assisted target gene transfer for cancer gene therapy. PMID- 27362776 TI - Number of children and later-life mortality among Finns born 1938-50. AB - We investigated the association between number of offspring and later-life mortality of Finnish men and women born 1938-50, and whether the association was explained by living conditions in own childhood and adulthood, chronic conditions, fertility timing, and unobserved characteristics common to siblings. We used a longitudinal 1950 census sample to estimate mortality at ages 50-72. Relative to parents of two children, all-cause mortality is highest among childless men and women, and elevated among those with one child, independently of observed confounders. Fixed-effect models, which control for unobserved characteristics shared by siblings, clearly support these findings among men. Cardiovascular mortality is higher among men with no, one, or at least four children than among those with two. Living conditions in adulthood contribute to the association between the number of children and mortality to a greater extent than childhood background, and chronic conditions contribute to the excess mortality of the childless. PMID- 27362777 TI - Stress and hypertensive disease: adrenals as a link. Experimental study on hypertensive ISIAH rat strain. AB - OBJECTIVE: Association between stress and hypertensive disease is still a matter of debate. Can stress be the cause of hypertensive disease and, if so, what mechanisms are involved? To clarify this question, the Inherited stress-induced arterial hypertensive rat strain (ISIAH rat strain) with a stress related arterial hypertension was developed by selection for the enhanced blood pressure response to 0.5 h restraint stress. The main intention of this work is to confirm that the adrenals are a main link between stress and hypertensive disease. METHODS: Hypertensive ISIAH and normotensive WAG rats have been studied. The in vivo secretion rate of corticosterone, aldosterone, 11-Deoxycorticosterone (DOC), and 11-dehydrocorticosterone was measured in anesthetized rats by adrenal vein cannulation. The Dexamethasone/Adrenocorticotropic hormone (DEX/ACTH) test was performed and mRNA expression of Cyp11b1 and Cyp11b2 genes in adrenals was evaluated by real-time PCR. RESULTS: An increased secretion rate of corticosterone and DOC and higher peripheral plasma aldosterone concentration in ISIAH rats were revealed. Response of plasma aldosterone to the surgical stress (adrenal vein cannulation) in the ISIAH rats was significantly higher. The increase of corticosterone and aldosterone in response to ACTH was also higher in hypertensive rats. The basal mRNA expression of both Cyp11b1 and Cyp11b2 genes was increased in the ISIAH rats. The ratio 11 dehydrocorticosterone/corticosterone in ISIAH rats was low which indicates the weakening of 11-beta-Hydroxysteroid dehydrogenase (11-beta-HSD) type 2 converting corticosterone to cortisone. CONCLUSION: ISIAH rats may serve as a living proof that stress may produce sustained hypertension, and genetically determined enhanced stress responsiveness of corticosterone and, especially, aldosterone may play a crucial role in the mechanism of hypertension development. PMID- 27362778 TI - Key steps and common pitfalls in developing and validating risk models. AB - : Models for estimating an individual's risk of having or developing a disease are abundant in the medical literature, yet many do not meet the methodological standards that have been set to maximise generalisability and utility. This paper presents an overview of ten steps from the conception of the study to the implementation of the risk model and discusses common pitfalls. We discuss crucial aspects of study design, data collection, model development and performance evaluation, and discuss how to bring the model to clinical practice. TWEETABLE ABSTRACT: We present an overview of ten key steps for the development of risk models and discuss common pitfalls. PMID- 27362779 TI - Forensic Analysis Reveals Acute Decompensation of Chronic Heart Failure in a 3500 Year-Old Egyptian Dignitary. AB - Naturally preserved and embalmed bodies from archeological contexts represent a powerful source of information for forensic investigators. They allow one to ascertain pathology, cause of death, to enhance diagnostic methodology, and to improve the analysis of altered remains. We investigated the complete head and lung remnants of a 3,500-year-old Egyptian dignitary by radiological, microscopic, and genetic approaches. The individual, a middle-aged male, suffered from severe periodontitis, mild atherosclerosis, and experienced cardiogenic pulmonary insufficiency with recurrent mini-bleeds and pulmonary edema. Histology and ancient DNA analyses excluded the presence of Mycobacterium tuberculosis or of any other pathogenic species. Based on our collection of evidence, we propose that acute decompensation complicating chronic cardiac insufficiency was the likely cause of death. The underlying causes for this failure remain unknown although chronic hypertension appears to be the most likely candidate. Our finding represents the earliest reported case of chronic heart failure in ancient mummies. PMID- 27362780 TI - Maternal touch and infant affect in the Still Face Paradigm: A cross-cultural examination. AB - Touch between mother and infant plays an important role in development starting from birth. Cross-cultural differences surrounding rearing practices have an influence on parent-infant interaction, including types of touch used and the development of emotional regulation. This study was designed to investigate maternal touch and infant emotional regulation in infant-mother dyads from Ecuador (n=25) and Hispanic dyads from the United States (US) (n=26). Mothers and their 4-month-old full-term infants participated in the Still Face Paradigm. Second-by-second coding of maternal touch and infant affect was completed. Overall the analyses showed that Ecuadorian mothers used more nurturing and accompaniment touch and less attention seeking touch than US Hispanic mothers during the pre-stressor (baseline) episode. Lagged multilevel models were used to investigate the effect of the different types of touch on infant emotional regulation in the groups for the episodes. The data suggest that playful touch had a significant increase in infant affect, whereas accompaniment and attention seeking touch had a significant decrease in infant affect. Overall, this study provides support for the role of touch in mother-infant synchronicity in relation to infant's emotional regulation. Identifying touch that is more calming is important to foster emotional regulation in infancy, which can have important implications for development. PMID- 27362782 TI - Social Support and Relationship Satisfaction as Moderators of the Stress-Mood Alcohol Link Association in US Navy Members. AB - The present study examined associations between stress and problematic alcohol use among US Navy members anticipating deployment, whether depressive symptoms mediated the stress-alcohol link, and whether social support and relationship satisfaction moderated associations between stress, depressive symptoms, and problematic alcohol use. Participants were 108 US Navy members assigned to an Arleigh Burke-class destroyer anticipating an 8-month deployment after Operational Enduring Freedom/Operation Iraqi Freedom. Stress was indirectly related to problematic alcohol use such that higher levels of stress were associated with higher levels of depressive symptoms, which were further associated with higher levels of alcohol use. The indirect effect of stress to problematic alcohol use via depressive symptoms was tested at different levels of social support and relationship satisfaction. At higher levels of social support and relationship satisfaction, the association between stress and problematic alcohol use via depressive symptoms decreased. Results help identify targets for alcohol prevention efforts among current military members. PMID- 27362781 TI - Lamina Cribrosa Microarchitecture in Monkey Early Experimental Glaucoma: Global Change. AB - PURPOSE: The purpose of this study was to characterize experimental glaucoma (EG) versus control eye differences in lamina cribrosa (LC), beam diameter (BD), pore diameter (PD), connective tissue volume fraction (CTVF), connective tissue volume (CTV), and LC volume (LV) in monkey early EG. METHODS: Optic nerve heads (ONHs) of 14 unilateral EG and 6 bilateral normal (BN) monkeys underwent three dimensional reconstruction and LC beam segmentation. Each beam and pore voxel was assigned a diameter based on the largest sphere that contained it before transformation to a common cylinder with inner, middle, and outer layers. Full thickness and layer averages for BD, PD, CTVF, CTV, and LV were calculated for each ONH. Beam diameter and PD distributions for each ONH were fit to a gamma distribution and summarized by scale and shape parameters. Experimental glaucoma and depth effects were assessed for each parameter by linear mixed-effects (LME) modeling. Animal-specific EG versus control eye differences that exceeded the maximum intereye difference among the six BN animals were considered significant. RESULTS: Overall EG eye mean PD was 12.8% larger (28.2 +/- 5.6 vs. 25.0 +/- 3.3 MUm), CTV was 26.5% larger (100.06 +/- 47.98 vs. 79.12 +/- 28.35 * 106 MUm3), and LV was 40% larger (229.29 +/- 98.19 vs. 163.63 +/- 39.87 * 106 MUm3) than control eyes (P <= 0.05, LME). Experimental glaucoma effects were significantly different by layer for PD (P = 0.0097) and CTVF (P < 0.0001). Pore diameter expanded consistently across all PDs. Experimental glaucoma eye-specific parameter change was variable in magnitude and direction. CONCLUSIONS: Pore diameter, CTV, and LV increase in monkey early EG; however, EG eye-specific change is variable and includes both increases and decreases in BD and CTVF. PMID- 27362784 TI - Predictors of dengue severity. PMID- 27362783 TI - Air Pollution and Subtypes, Severity and Vulnerability to Ischemic Stroke-A Population Based Case-Crossover Study. AB - BACKGROUND AND PURPOSE: Few studies have examined the association between air pollutants and ischemic stroke subtypes. We examined acute effects of outdoor air pollutants (PM10, NO2, O3, CO, SO2) on subtypes and severity of incident ischemic stroke and investigated if pre-existing risk factors increased susceptibility. METHODS: We used a time stratified case-crossover study and stroke cases from the South London Stroke Register set up to capture all incident cases of first ever stroke occurring amongst residents in a geographically defined area. The Oxford clinical and TOAST etiological classifications were used to classify subtypes. A pragmatic clinical classification system was used to assess severity. Air pollution concentrations from the nearest background air pollution monitoring stations to patients' residential postcode centroids were used. Lags from 0 to 6 days were investigated. RESULTS: There were 2590 incident cases of ischemic stroke (1995-2006). While there were associations at various lag times with several pollutants, overall, there was no consistent pattern between exposure and risk of ischemic stroke subtypes or severity. The possible exception was the association between NO2 exposure and small vessel disease stroke-adjusted odds ratio of 1.51 (1.12-2.02) associated with an inter-quartile range increase in the lag 0-6 day average for NO2. There were no clear associations in relation to pre existing risk factors. CONCLUSIONS: Overall, we found little consistent evidence of association between air pollutants and ischemic stroke subtypes and severity. There was however a suggestion that increasing NO2 exposure might be associated with higher risk of stroke caused by cerebrovascular small vessel disease. PMID- 27362785 TI - Nutritional quality of dietary patterns of children: are there differences inside and outside school? AB - OBJECTIVES: To describe the dietary patterns of children inside and outside school and investigate their associations with sociodemographic factors and nutritional status. METHODS: This was a multicenter cross-sectional study in which children of both sexes, aged 1-6 years, attending private and public daycare centers and preschools in Brazil, were evaluated (n=2979). Demographic, socioeconomic and dietary data (weighed food records and estimated food records) were collected. Dietary patterns were derived by factor analysis from 36 food groups. RESULTS: Four dietary patterns were identified inside school, and three outside. Inside school, the "traditional" pattern was associated to low income and presented high nutritional quality. The "dual" pattern was associated with low income and with high intake of added sugar and glycemic load. The "snack" pattern was associated with children enrolled at private schools and with high intake of added sugar and glycemic load. The "bread and butter" pattern was associated with high intake of added sugar and trans fat. Outside school, the "traditional" pattern was associated with high intake of saturated fat, trans fats, sodium, and total fiber. The "bread and butter" pattern was associated with high intake of trans fats and glycemic load, whereas the "snack" pattern was associated with overweight, private schools, high income, and high intake of trans fats, sodium, and total fiber. CONCLUSION: There are differences in the nutritional quality of dietary patterns inside and outside school, and heterogeneity in adherence to these patterns were observed across regions and socioeconomic classes. PMID- 27362786 TI - Optical response of the Cu2 S2 diamond core in Cu2II(NGuaS)2 Cl2. AB - Density functional theory (DFT) and time-dependent DFT calculations are presented for the dicopper thiolate complex Cu2 (NGuaS)2 Cl2 [NGuaS=2-(1,1,3,3 tetramethylguanidino) benzenethiolate] with a special focus on the bonding mechanism of the Cu2 S2 Cl2 core and the spectroscopic response. This complex is relevant for the understanding of dicopper redox centers, for example, the CuA center. Its UV/Vis absorption is theoretically studied and found to be similar to other structural CuA models. The spectrum can be roughly divided in the known regions of metal d-d absorptions and metal to ligand charge transfer regions. Nevertheless the chloride ions play an important role as electron donors, with the thiolate groups as electron acceptors. The bonding mechanism is dissected by means of charge decomposition analysis which reveals the large covalency of the Cu2 S2 diamond core mediated between Cu dz2 and S-S pi and pi* orbitals forming Cu-S sigma bonds. Measured resonant Raman spectra are shown for 360- and 720-nm excitation wavelength and interpreted using the calculated vibrational eigenmodes and frequencies. The calculations help to rationalize the varying resonant behavior at different optical excitations. Especially the phenylene rings are only resonant for 720 nm. (c) 2016 Wiley Periodicals, Inc. PMID- 27362787 TI - TORquing metabolic reprogramming in cancer cells. PMID- 27362789 TI - Design and screening of a chimeric survivin-specific nanobody and its anticancer activities in vitro. AB - Survivin is a strong inhibitor of apoptosis protein and a promising target for cancer prevention and treatment. Here, we report the design and preparation of novel chimeric nanobodies (Nbs) that could specifically bind to survivin. We screened the peptides from phage-displayed libraries (7-mer, 12-mer) for nonconserved sequences of complementarity-determining regions (CDRs) in the scaffold of the Nb. By a combination of the nonconserved sequences for CDRs, the corresponding chimeric Nbs (10 Nbs) were prepared with genetic operations. The antisurvivin Nb TAT-Nb4A (a fusion with cellular transduction peptide TAT) was found to be the most efficient antibody on the basis of the results from enzyme linked immunosorbent assay, MTT, and flow cytometry when these nanobodies were tested with hepatoma carcinoma cell HepG2. TAT-Nb4A could inhibit the growth of HepG2 and promote cancer cell apoptosis significantly in a dose-dependent and time-dependent manner: the apoptosis rate reached 52.5% when the concentration of TAT-Nb4A was 120 MUg/ml. Western blotting with cells expressing survivin showed that the prepared nanobody could efficiently bind to expressed survivin and blocked the signaling pathway in which survivin played a role. This study provided a convenient and feasible method of obtaining a novel specific Nb with the case of survivin as a good example. PMID- 27362788 TI - Project Gel a Randomized Rectal Microbicide Safety and Acceptability Study in Young Men and Transgender Women. AB - OBJECTIVES: The purpose of Project Gel was to determine the safety and acceptability of rectal microbicides in young men who have sex with men (MSM) and transgender women (TGW) at risk of HIV infection. METHODS: MSM and TGW aged 18-30 years were enrolled at three sites; Pittsburgh, PA; Boston, MA; and San Juan, PR. Stage 1A was a cross-sectional assessment of sexual health and behavior in MSM and TGW. A subset of participants from Stage 1A were then enrolled in Stage 1B, a 12-week evaluation of the safety and acceptability of a placebo rectal gel. This was followed by the final phase of the study (Stage 2) in which a subset of participants from Stage 1B were enrolled into a Phase 1 rectal safety and acceptability evaluation of tenofovir (TFV) 1% gel. RESULTS: 248 participants were enrolled into Stage 1A. Participants' average age was 23.3 years. The most common sexually transmitted infection (STIs) at baseline were Herpes simplex (HSV)-2 (16.1% by serology) and rectal Chlamydia trachomatis (CT) (10.1% by NAAT). 134 participants were enrolled into Stage 1B. During the 12 week period of follow-up 2 HIV, 5 rectal CT, and 5 rectal Neisseria gonorrhea infections were detected. The majority of adverse events (AEs) were infections (N = 56) or gastrointestinal (N = 46) and were mild (69.6%) or moderate (28.0%). Of the participants who completed Stage 1B, 24 were enrolled into Stage 2 and randomized (1:1) to receive TFV or placebo gel. All participants completed Stage 2. The majority of AEs were gastrointestinal (N = 10) and of mild (87.2%) or moderate (10.3%) severity. CONCLUSIONS: In this study we were able to enroll a sexually active population of young MSM and TGW who were willing to use rectal microbicides. TFV gel was safe and acceptable and should be further developed as an alternative HIV prevention intervention for this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT01283360. PMID- 27362790 TI - 8-Farnesyloxycoumarin induces apoptosis in PC-3 prostate cancer cells by inhibition of 15-lipoxygenase-1 enzymatic activity. AB - Prostate cancer is the second most common cancer in men worldwide. Overexpression of 15-lipoxygenase-1 (15-LOX-1) has been reported in prostate cancer patients. This study aimed to investigate the cytotoxic and anticancer effects of 8 farnesyloxycoumarin (8f), a prenylated coumarin, by inhibition of 15-LOX-1 activity, in prostate cancer cells. The activity of 15-LOX-1 and the inhibitory effects of 8f on this enzyme were first assessed in PC-3 and DU145 prostate cancer cells. The MTT assay was used to examine the cytotoxicity effects of 8f on PC-3 cells following 15-LOX-1 inhibition. To determine the type of cell death, chromatin condensation and DNA damage were examined by DAPI staining and comet assay, respectively. Furthermore, the effects of 8f on the cell cycle were evaluated by PI staining and flow cytometry. The activity of 15-LOX-1 was determined to be higher in PC-3 compared with DU145 cells; thus, this cell line was selected for further experiments. 8f induced cell death in PC-3 cells in a dose-dependent and time-dependent manner, with IC50 values similar to cisplatin, which was used as a control. However, 8f did not significantly affect the viability of HFF3, human foreskin fibroblast cells, under identical conditions. The appearance of apoptotic cells after 8f treatment was confirmed by the presence of PC-3 cells containing condensed chromatin as shown by DAPI staining. The comet assay indicated the induction of DNA damage in cancerous cells compared with normal cells. In addition, 8f induced a potent G1 cell-cycle arrest in PC-3 cells. Our results showed that the antitumor effects of 8f on PC-3 cells were promoted by apoptosis induction, probably via inhibition of 15-LOX-1 activity, thus suggesting that 8f may have therapeutic value in prostate cancer treatment. PMID- 27362791 TI - Attention bias dynamics and symptom severity during and following CBT for social anxiety disorder. AB - OBJECTIVE: Threat-related attention bias figures prominently in contemporary accounts of the maintenance of anxiety disorders, yet longitudinal intervention research relating attention bias to anxiety symptom severity is limited. Capitalizing on recent advances in the conceptualization and measurement of attention bias, we aimed to examine the relation between attention bias, indexed using trial-level bias scores (TLBSs) to quantify temporal dynamics reflecting dysregulation of attentional processing of threat (as opposed to aggregated mean bias scores) and social anxiety symptom severity over the course of cognitive behavioral therapy (CBT) and 1-month follow-up. METHOD: Adults with social anxiety disorder (N = 39) assigned to either yohimbine- or placebo-augmented CBT completed measures of attention bias and social anxiety symptom severity weekly throughout CBT (5 sessions) and at 1-week and 1-month posttreatment. RESULTS: TLBSs of attention bias temporal dynamics showed stronger psychometric properties than mean aggregated scores and were highly interrelated, in line with within subject temporal variability fluctuating in time between attentional overengagement and strategic avoidance from threat. Attention bias toward threat and temporal variability in attention bias (i.e., attentional dysregulation), but not attention bias away from threat, significantly reduced over the course of CBT. Cross-lag analyses revealed no evidence of a causal relation between reductions in attentional dysregulation leading to symptom severity reduction, or vice versa. Observed relations did not vary as a function of time. CONCLUSIONS: We found no evidence for attentional dysregulation as a causal mechanism for symptom reduction in CBT for social anxiety disorders. Implications for future research are discussed. (PsycINFO Database Record PMID- 27362792 TI - Internet-delivered cognitive control training as a preventive intervention for remitted depressed patients: Evidence from a double-blind randomized controlled trial study. AB - BACKGROUND: Cognitive control impairments may place remitted depressed (RMD) patients at increased risk for developing future depressive symptomatology by disrupting emotion regulation processes. Research has shown that directly targeting cognitive control has beneficial effects on high trait ruminators and clinically depressed patients. The current study tested whether internet delivered cognitive control training (CCT) can be used as an intervention to increase resilience to depression in RMD patients. METHOD: Effects of CCT were assessed using a double-blind randomized controlled design. RMD patients performed 10 sessions of a working memory-based CCT (N = 34) or a low cognitive load training (N = 34; active control condition) over a period of 14 days. Assessments took place prior to training, immediately following 2 weeks of training, and at 3 months follow-up. Brooding and depressive symptomatology were selected as primary outcome measures, alternative indicators for emotion regulation and residual symptomatology were selected as secondary outcome measures, along with indicators of functioning. RESULTS: Compared to an active control condition, CCT demonstrated beneficial effects on a cognitive transfer task, brooding, depressive symptomatology, residual complaints, self-reported use of general maladaptive emotion regulation strategies, and resilience after controlling for intention to treat. Furthermore, completers of the CCT reported a reduction in experienced disability and cognitive complaints. However, no beneficial effects were found for self-reported use of adaptive emotion regulation strategies. CONCLUSIONS: These findings demonstrate the effectiveness of CCT as an intervention to reduce cognitive vulnerability, residual symptomatology, and foster resilience following recovery from depression. CCT thus holds potential as a preventive intervention for RMD patients. (PsycINFO Database Record PMID- 27362793 TI - Diagnosis of chronic lymphoproliferative disorders by flow cytometry using four color combinations for immunophenotyping: A proposal of the brazilian group of flow cytometry (GBCFLUX). AB - BACKGROUND: Multiparametric flow cytometry (MFC) is a powerful tool for the diagnosis of hematological malignancies and has been useful for the classification of chronic lymphoproliferative disorders (CLPD) according to the WHO criteria. Following the purposes of the Brazilian Group of Flow Cytometry (GBCFLUX), the aim of this report was to standardize the minimum requirements to achieve an accurate diagnosis in CLPDs, considering the different economic possibilities of the laboratories in our country. Most laboratories in Brazil work with 4-fluorescence flow cytometers, which is why the GBCFLUX CLPD Committee has proposed 4-color monoclonal antibody (MoAb) panels. METHODS/RESULTS: Panels for screening and diagnosis in B, T and NK lymphoproliferative disorders were developed based on the normal differentiation pathways of these cells and the most frequent phenotypic aberrations. Important markers for prognosis and for minimal residual disease (MRD) evaluation were also included. The MoAb panels presented here were designed based on the diagnostic expertise of the participating laboratories and an extensive literature review. CONCLUSION: The 4 color panels presented to aid in the diagnosis of lymphoproliferative neoplasms by GBCFLUX aim to provide clinical laboratories with a systematic, step-wise, cost-effective, and reproducible approach to obtain an accurate immunophenotypic diagnosis of the most frequent of these disorders. (c) 2016 International Clinical Cytometry Society. PMID- 27362794 TI - Circulating MicroRNAs: Association with Lung Function in Asthma. AB - BACKGROUND: MicroRNAs are key transcriptional and network regulators previously associated with asthma susceptibility. However, their role in relation to asthma severity has not been delineated. OBJECTIVE: We hypothesized that circulating microRNAs could serve as biomarkers of changes in lung function in asthma patients. METHODS: We isolated microRNAs from serum samples obtained at randomization for 160 participants of the Childhood Asthma Management Program. Using a TaqMan microRNA array containing 754 microRNA primers, we tested for the presence of known asthma microRNAs, and assessed the association of the individual microRNAs with lung function as measured by FEV1/FVC, FEV1% and FVC%. We further tested the subset of FEV1/FVC microRNAs for sex-specific and lung developmental associations. RESULTS: Of the 108 well-detected circulating microRNAs, 74 (68.5%) had previously been linked to asthma susceptibility. We found 22 (20.3%), 4 (3.7%) and 8 (7.4%) microRNAs to be associated with FEV1/FVC, FEV1% and FVC%, respectively. 8 (of 22) FEV1/FVC, 3 (of 4) FEV1% and 1 (of 8) FVC% microRNAs had functionally validated target genes that have been linked via genome wide association studies to asthma and FEV1 change. Among the 22 FEV1/FVC microRNAs, 9 (40.9%) remain associated with FEV1/FVC in boys alone in a sex stratified analysis (compared with 3 FEV1/FVC microRNAs in girls alone), 7 (31.8%) were associated with fetal lung development, and 3 (13.6%) in both. Ontology analyses revealed enrichment for pathways integral to asthma, including PPAR signaling, G-protein coupled signaling, actin and myosin binding, and respiratory system development. CONCLUSIONS: Circulating microRNAs reflect asthma biology and are associated with lung function differences in asthmatics. They may represent biomarkers of asthma severity. PMID- 27362795 TI - Epitope Mapping of Avian Influenza M2e Protein: Different Species Recognise Various Epitopes. AB - A common approach for developing diagnostic tests for influenza virus detection is the use of mouse or rabbit monoclonal and/or polyclonal antibodies against a target antigen of the virus. However, comparative mapping of the target antigen using antibodies from different animal sources has not been evaluated before. This is important because identification of antigenic determinants of the target antigen in different species plays a central role to ensure the efficiency of a diagnostic test, such as competitive ELISA or immunohistochemistry-based tests. Interest in the matrix 2 ectodomain (M2e) protein of avian influenza virus (AIV) as a candidate for a universal vaccine and also as a marker for detection of virus infection in vaccinated animals (DIVA) is the rationale for the selection of this protein for comparative mapping evaluation. This study aimed to map the epitopes of the M2e protein of avian influenza virus H5N1 using chicken, mouse and rabbit monoclonal or monospecific antibodies. Our findings revealed that rabbit antibodies (rAbs) recognized epitope 6EVETPTRN13 of the M2e, located at the N-terminal of the protein, while mouse (mAb) and chicken antibodies (cAbs) recognized epitope 10PTRNEWECK18, located at the centre region of the protein. The findings highlighted the difference between the M2e antigenic determinants recognized by different species that emphasized the importance of comparative mapping of antibody reactivity from different animals to the same antigen, especially in the case of multi-host infectious agents such as influenza. The findings are of importance for antigenic mapping, as well as diagnostic test and vaccine development. PMID- 27362796 TI - Targeting long non-coding RNA-TUG1 inhibits tumor growth and angiogenesis in hepatoblastoma. AB - Hepatoblastoma is the most common liver tumor of early childhood, which is usually characterized by unusual hypervascularity. Recently, long non-coding RNAs (lncRNA) have emerged as gene regulators and prognostic markers in several cancers, including hepatoblastoma. We previously reveal that lnRNA-TUG1 is upregulated in hepatoblastoma specimens by microarray analysis. In this study, we aim to elucidate the biological and clinical significance of TUG1 upregulation in hepatoblastoma. We show that TUG1 is significantly upregulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. TUG1 knockdown inhibits tumor growth and angiogenesis in vivo, and decreases hepatoblastoma cell viability, proliferation, migration, and invasion in vitro. TUG1, miR-34a-5p, and VEGFA constitutes to a regulatory network, and participates in regulating hepatoblastoma cell function, tumor progression, and tumor angiogenesis. Overall, our findings indicate that TUG1 upregulation contributes to unusual hypervascularity of hepatoblastoma. TUG1 is a promising therapeutic target for aggressive, recurrent, or metastatic hepatoblastoma. PMID- 27362797 TI - TSC but not PTEN loss in starving cones of retinitis pigmentosa mice leads to an autophagy defect and mTORC1 dissociation from the lysosome. AB - Understanding the mechanisms that contribute to secondary cone photoreceptor loss in retinitis pigmentosa (RP) is critical to devise strategies to prolong vision in this neurodegenerative disease. We previously showed that constitutive activation of the mammalian target of rapamycin complex 1 (mTORC1), by loss of its negative regulator the tuberous sclerosis complex protein 1 (Tsc1; also known as Hamartin), was sufficient to promote robust survival of nutrient-stressed cones in two mouse models of RP by improving glucose uptake and utilization. However, while cone protection remained initially stable for several weeks, eventually cone loss resumed. Here we show that loss of Tsc1 in the cones of RP mice causes a defect in autophagy, leading to the accumulation of ubiquitinated aggregates. We demonstrate that this defect was not due to an inhibition of autophagy initiation, but due to an accumulation of autolysosomes, suggesting a defect in the end-stage of the process causing an amino-acid shortage in cones, thereby hampering long-term cone survival. Because cells with TSC loss fail to completely inhibit mTORC1 and properly activate autophagy in the absence of amino acids, we sporadically administered the mTORC1 inhibitor rapamycin, which was sufficient to correct the defects seen in cones, further enhancing the efficiency of cone survival mediated by Tsc1 loss. Concordantly, activation of mTORC1 by loss of the phosphatase and tensin homolog (Pten) did not affect autophagy and amino-acid metabolism, leading to a more sustained long-term protection of cones. As loss of Pten, which in cones results in less robust mTORC1 activation when compared with loss of Tsc1, still affords long-term cone survival, therapeutic interventions with mTORC1 activators or gene therapy with selected mTORC1 targets that improve glucose metabolism are potential strategies to delay vision loss in patients with RP. PMID- 27362798 TI - ZnCl2 sustains the adriamycin-induced cell death inhibited by high glucose. AB - Hyperglycemia, the condition of high blood glucose, is typical of diabetes and obesity and represents a significant clinical problem. The relationship between hyperglycemia and cancer risk has been established by several studies. Moreover, hyperglycemia has been shown to reduce cancer cell response to therapies, conferring resistance to drug-induced cell death. Therefore, counteracting the negative effects of hyperglycemia may positively improve the cancer cell death induced by chemotherapies. Recent studies showed that zinc supplementation may have beneficial effects on glycemic control. Here we aimed at evaluating whether ZnCl2 could counteract the high-glucose (HG) effects and consequently restore the drug-induced cancer cell death. At the molecular level we found that the HG induced expression of genes known to be involved in chemoresistance (such as HIF 1alpha, GLUT1, and HK2 glycolytic genes, as well as NF-kappaB activity) was reduced by ZnCl2 treatment. In agreement, the adryamicin (ADR)-induced apoptotic cancer cell death was significantly impaired by HG and efficiently re-established by ZnCl2 cotreatment. Mechanistically, the ADR-induced c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) phosphorylation, inhibited by HG, was efficiently restored by ZnCl2. The JNK involvement in apoptotic cell death was assessed by the use of JNK dominant-negative expression vector that indeed impaired the ZnCl2 ability to restore drug-induced cell death in HG condition. Altogether, these findings indicate that ZnCl2 supplementation efficiently restored the drug-induced cancer cell death, inhibited by HG, by both sustaining JNK activation and counteracting the glycolytic pathway. PMID- 27362799 TI - Does murine spermatogenesis require WNT signalling? A lesson from Gpr177 conditional knockout mouse models. AB - Wingless-related MMTV integration site (WNT) proteins and several other components of the WNT signalling pathway are expressed in the murine testes. However, mice mutant for WNT signalling effector beta-catenin using different Cre drivers have phenotypes that are inconsistent with each other. The complexity and overlapping expression of WNT signalling cascades have prevented researchers from dissecting their function in spermatogenesis. Depletion of the Gpr177 gene (the mouse orthologue of Drosophila Wntless), which is required for the secretion of various WNTs, makes it possible to genetically dissect the overall effect of WNTs in testis development. In this study, the Gpr177 gene was conditionally depleted in germ cells (Gpr177(flox/flox), Mvh-Cre; Gpr177(flox/flox), Stra8-Cre) and Sertoli cells (Gpr177(flox/flox), Amh-Cre). No obvious defects in fertility and spermatogenesis were observed in these three Gpr177 conditional knockout (cKO) mice at 8 weeks. However, late-onset testicular atrophy and fertility decline in two germ cell-specific Gpr177 deletion mice were noted at 8 months. In contrast, we did not observe any abnormalities of spermatogenesis and fertility, even in 8 month-old Gpr177(flox/flox), Amh-Cre mice. Elevation of reactive oxygen species (ROS) was detected in Gpr177 cKO germ cells and Sertoli cells and exhibited an age-dependent manner. However, significant increase in the activity of Caspase 3 was only observed in germ cells from 8-month-old germ cell-specific Gpr177 knockout mice. In conclusion, GPR177 in Sertoli cells had no apparent influence on spermatogenesis, whereas loss of GPR177 in germ cells disrupted spermatogenesis in an age-dependent manner via elevating ROS levels and triggering germ cell apoptosis. PMID- 27362800 TI - Transferrin receptor facilitates TGF-beta and BMP signaling activation to control craniofacial morphogenesis. AB - The Pierre Robin Sequence (PRS), consisting of cleft palate, glossoptosis and micrognathia, is a common human birth defect. However, how this abnormality occurs remains largely unknown. Here we report that neural crest cell (NCC) specific knockout of transferrin receptor (Tfrc), a well known transferrin transporter protein, caused micrognathia, cleft palate, severe respiratory distress and inability to suckle in mice, which highly resemble human PRS. Histological and anatomical analysis revealed that the cleft palate is due to the failure of palatal shelves elevation that resulted from a retarded extension of Meckel's cartilage. Interestingly, Tfrc deletion dramatically suppressed both transforming growth factor-beta (TGF-beta) and bone morphogenetic protein (BMP) signaling in cranial NCCs-derived mandibular tissues, suggesting that Tfrc may act as a facilitator of these two signaling pathways during craniofacial morphogenesis. Together, our study uncovers an unknown function of Tfrc in craniofacial development and provides novel insight into the etiology of PRS. PMID- 27362801 TI - Extracellular DNA traps released by acute promyelocytic leukemia cells through autophagy. AB - Acute promyelocytic leukemia (APL) cells exhibit disrupted regulation of cell death and differentiation, and therefore the fate of these leukemic cells is unclear. Here, we provide the first evidence that a small percentage of APL cells undergo a novel cell death pathway by releasing extracellular DNA traps (ETs) in untreated patients. Both APL and NB4 cells stimulated with APL serum had nuclear budding of vesicles filled with chromatin that leaked to the extracellular space when nuclear and cell membranes ruptured. Using immunofluorescence, we found that NB4 cells undergoing ETosis extruded lattice-like structures with a DNA-histone backbone. During all-trans retinoic acid (ATRA)-induced cell differentiation, a subset of NB4 cells underwent ETosis at days 1 and 3 of treatment. The levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were significantly elevated at 3 days, and combined treatment with TNF-alpha and IL-6 stimulated NB4 cells to release ETs. Furthermore, inhibition of autophagy by pharmacological inhibitors or by small interfering RNA against Atg7 attenuated LC3 autophagy formation and significantly decreased ET generation. Our results identify a previously unrecognized mechanism for death in promyelocytes and suggest that ATRA may accelerate ET release through increased cytokines and autophagosome formation. Targeting this cellular death pathway in addition to conventional chemotherapy may provide new therapeutic modalities for APL. PMID- 27362802 TI - A HIF-1alpha-driven feed-forward loop augments HIF signalling in Hep3B cells by upregulation of ARNT. AB - Oxygen-deprived (hypoxic) areas are commonly found within neoplasms caused by excessive cell proliferation. The transcription factor Aryl hydrocarbon receptor nuclear translocator (ARNT) is part of the hypoxia-inducible factor (HIF) pathway, which mediates adaptive responses to ensure cellular survival under hypoxic conditions. HIF signalling leads to metabolic alterations, invasion/metastasis and the induction of angiogenesis in addition to radio chemoresistance of tumour cells. Activation of the HIF pathway is based on the abundance of HIF-alpha subunits, which are regulated in an oxygen-dependent manner and form transcriptional active complexes with ARNT or ARNT2 (also referred as HIF-1beta and HIF-2beta, respectively). ARNT is considered to be unaffected by hypoxia but certain cell lines, including Hep3B cells, are capable to elevate this transcription factor in response to oxygen deprivation, which implies an advantage. Therefore, the aim of this study was to elucidate the mechanism of hypoxia-dependent ARNT upregulation and to determine implications on HIF signalling. Gene silencing and overexpression techniques were used to alter the expression pattern of HIF transcription factors under normoxic and hypoxic conditions. qRT-PCR and western blotting were performed to measure gene and protein expression, respectively. HIF activity was determined by reporter gene assays. The results revealed a HIF-1alpha-dependent mechanism leading to ARNT upregulation in hypoxia. Forced expression of ARNT increased reporter activity under normoxic and hypoxic conditions. In conclusion, these findings indicate a novel feed-forward loop and suggest that ARNT might be a limiting factor. Augmented HIF signalling in terms of elevated target gene expression might be advantageous for tumour cells. PMID- 27362803 TI - The contribution of arachidonate 15-lipoxygenase in tissue macrophages to adipose tissue remodeling. AB - Cellular plasticity in adipose tissue involves adipocyte death, its clearance, and de novo adipogenesis, enabling homeostatic turnover and adaptation to metabolic challenges; however, mechanisms regulating these serial events are not fully understood. The present study investigated the roles of arachidonate 15 lipoxygenase (Alox15) in the clearance of dying adipocytes by adipose tissue macrophages. First, upregulation of Alox15 expression and apoptotic adipocyte death in gonadal white adipose tissue (gWAT) were characterized during adipose tissue remodeling induced by beta3-adrenergic receptor stimulation. Next, an in vitro reconstruction of adipose tissue macrophages and apoptotic adipocytes recapitulated adipocyte clearance by macrophages and demonstrated that macrophages co-cultured with apoptotic adipocytes increased the expression of efferocytosis-related genes. Genetic deletion and pharmacological inhibition of Alox15 diminished the levels of adipocyte clearance by macrophages in a co culture system. Gene expression profiling of macrophages isolated from gWAT of Alox15 knockout (KO) mice demonstrated distinct phenotypes, especially downregulation of genes involved in lipid uptake and metabolism compared to wild type mice. Finally, in vivo beta3-adrenergic stimulation in Alox15 KO mice failed to recruit crown-like structures, a macrophage network clearing dying adipocytes in gWAT. Consequently, in Alox15 KO mice, proliferation/differentiation of adipocyte progenitors and beta3-adrenergic remodeling of gWAT were impaired compared to wild-type control mice. Collectively, our data established a pivotal role of Alox15 in the resolution of adipocyte death and in adipose tissue remodeling. PMID- 27362804 TI - AKT activation controls cell survival in response to HDAC6 inhibition. AB - HDAC6 is emerging as an important therapeutic target for cancer. We investigated mechanisms responsible for survival of tumor cells treated with a HDAC6 inhibitor. Expression of the 20 000 genes examined did not change following HDAC6 treatment in vivo. We found that HDAC6 inhibition led to an increase of AKT activation (P-AKT) in vitro, and genetic knockdown of HDAC6 phenocopied drug induced AKT activation. The activation of AKT was not observed in PTEN null cells; otherwise, PTEN/PIK3CA expression per se did not predict HDAC6 inhibitor sensitivity. Interestingly, HDAC6 inhibitor treatment led to inactivating phosphorylation of PTEN (P-PTEN Ser380), which likely led to the increased P-AKT in cells that express PTEN. Synergy was observed with phosphatidylinositol 3' kinases (PI3K) inhibitor treatment in vitro, accompanied by increased caspase 3/7 activity. Furthermore, combination of HDAC6 inhibitor with a PI3K inhibitor caused substantial tumor growth inhibition in vivo compared with either treatment alone, also detectable by Ki-67 immunostaining and (18)F-FLT positron emission tomography (PET). In aggregate AKT activation appears to be a key survival mechanism for HDAC6 inhibitor treatment. Our findings indicate that dual inhibition of HDAC6 and P-AKT may be necessary to substantially inhibit growth of solid tumors. PMID- 27362805 TI - Tubular epithelial cells in renal clear cell carcinoma express high RIPK1/3 and show increased susceptibility to TNF receptor 1-induced necroptosis. AB - We previously reported that renal clear cell carcinoma cells (RCC) express both tumor necrosis factor receptor (TNFR)-1 and -2, but that, in organ culture, a TNF mutein that only engages TNFR1, but not TNFR2, causes extensive cell death. Some RCC died by apoptosis based on detection of cleaved caspase 3 in a minority TUNEL positive cells but the mechanism of death in the remaining cells was unexplained. Here, we underpin the mechanism of TNFR1-induced cell death in the majority of TUNEL-positive RCC cells, and show that they die by necroptosis. Malignant cells in high-grade tumors displayed threefold to four fold higher expression of both receptor-interacting protein kinase (RIPK)1 and RIPK3 compared with non-tumor kidney tubular epithelium and low-grade tumors, but expression of both enzymes was induced in lower grade tumors in organ culture in response to TNFR1 stimulation. Furthermore, TNFR1 activation induced significant MLKL(Ser358) and Drp1(Ser616) phosphorylation, physical interactions in RCC between RIPK1-RIPK3 and RIPK3-phospho-MLKL(Ser358), and coincidence of phospho-MLKL(ser358) and phospho-Drp1(Ser616) at mitochondria in TUNEL-positive RCC. A caspase inhibitor only partially reduced the extent of cell death following TNFR1 engagement in RCC cells, whereas three inhibitors, each targeting a different step in the necroptotic pathway, were much more protective. Combined inhibition of caspases and necroptosis provided additive protection, implying that different subsets of cells respond differently to TNF-alpha, the majority dying by necroptosis. We conclude that most high-grade RCC cells express increased amounts of RIPK1 and RIPK3 and are poised to undergo necroptosis in response to TNFR1 signaling. PMID- 27362806 TI - MDM2 facilitates adipocyte differentiation through CRTC-mediated activation of STAT3. AB - The ubiquitin ligase MDM2 is best known for balancing the activity of the tumor suppressor p53. We have previously shown that MDM2 is vital for adipocyte conversion through controlling Cebpd expression in a p53-independent manner. Here, we show that the proadipogenic effect of MDM2 relies on activation of the STAT family of transcription factors. Their activation was required for the cAMP mediated induction of target genes. Interestingly, rather than influencing all cAMP-stimulated genes, inhibition of the kinases directly responsible for STAT activation, namely JAKs, or ablation of MDM2, each resulted in abolished induction of a subset of cAMP-stimulated genes, with Cebpd being among the most affected. Moreover, STATs were able to interact with the transcriptional cofactors CRTC2 and CRTC3, hitherto only reported to associate with the cAMP responsive transcription factor CREB. Last but not least, the binding of CRTC2 to a transcriptional enhancer that interacts with the Cebpd promoter was dramatically decreased upon JAK inhibition. Our data reveal the existence of an unusual functional interplay between STATs and CREB at the onset of adipogenesis through shared CRTC cofactors. PMID- 27362807 TI - TC-N19, a novel dual inhibitor of EGFR and cMET, efficiently overcomes EGFR-TKI resistance in non-small-cell lung cancer cells. AB - Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) show a clinical benefit when used to treat patients with EGFR-mutated non-small-cell lung cancer (NSCLC), but this treatment unfortunately fails in patients with TKI resistant tumors. We here provide evidence that TC-N19 (N19), a novel dual inhibitor of EGFR and cMET, efficiently overcomes the EGFR-TKI resistance in EGFR mutated NSCLC cells via simultaneous degradation of both proteins by ubiquitin proteasomes. Comparison with HSP90 inhibitor treatment and knockdown of EGFR and cMET by small hairpin RNAs reveal that the reduction of EGFR and cMET expression by N19 is responsible for overcoming the intrinsic TKI resistance mediated by paxillin (PXN) in high PXN-expressing cells, PXN-overexpressing PC9 cells (PC9 PXN), the EGFR-T790M-mediated TKI resistance in H1975 and CL97 cells, and the acquired resistance to gefitinib in gefitinib-resistant PC9 cells (PC9GR). Annexin V-PI staining assay showed that the induction of apoptosis in NSCLC cells by N19 depended on the reduction in levels of both proteins. Xenograft tumor formation in nude mice induced by a PC9-PXN-stable clone and by PC9GR cells was nearly completely suppressed by N19 treatment, with no changes in animal body weight. MTT assays of normal lung cells and reticulocytes showed no cytotoxicity responses to N19. In summary, N19 may act as a novel dual inhibitor of EGFR and cMET that induces apoptosis in TKI-resistant EGFR-mutated NSCLC cells and suppresses xenograft tumor formation. We suggest that N19 may be a potential new generation TKI or HSP90 inhibitor used for treatment of NSCLC patients who show resistance to current TKI-targeting therapies. PMID- 27362809 TI - Patients' expectations assessment in orthodontic treatment: findings from a questionnaire survey. AB - BACKGROUND: The aim of this study was to analyze the psychological aspects of patients during their orthodontic treatment, evaluating their expectations during treatment comparing Greek patients to Italian patients. METHODS: This cross sectional descriptive study involved a sample of 228 patients (113 Italians -115 Greeks) undergoing fixed or removable orthodontic treatment. A questionnaire comprising of six questions was used and patients scored each question on a 0-10 Scale. Participants completed a validated questionnaire measure of orthodontic expectations that was tested for reliability. Descriptive analysis of the responses was undertaken, and comparisons between boys and girls, as well as between Greek and Italian patients, was made. The expectation score was calculated by summarizing the 6 items (A1 to A6). Reliability Analysis was performed using the Item-test, Item-rest correlation and the Cronbach's alpha. Items with a Cronbach's alpha coefficients greater than 0.7 are considered acceptable. To investigate the effect of the City and Gender on the expectation score, an univariate analysis was carried out by the Wilcoxon Rank Sum Test. Differences, with a P value less than 0.05, were selected as significant. RESULTS: Overall expectation Cronbach's alpha coefficient (internal consistency) was 0.73 (95% CI: 0.64-0.81). The mean of expectation items was 7.8 (SD=1.8). A significant slight correlation was found between motivation (item A1) and main reason of treatment (item A3) (r=0.17; P=0.0122). Moreover, there was a significant moderate correlation between compliance (item A4) and expectation (item A6) (r=0. 58; P<0.0001). CONCLUSIONS: Male showed a significant higher overall score compared to female sample, as well as Greek patients compared to Italians. PMID- 27362810 TI - The use of a collagenated porcine cortical lamina in the reconstruction of alveolar ridge defects. A clinical and histological study. AB - BACKGROUND: Alveolar ridge reconstruction by means of resorbable and non resorbable membranes has been proposed to increase the hard tissue volume in deficient sites. The purpose of this study was therefore to clinically and histologically evaluate the use of collagenated porcine bone lamina in case of horizontal and vertical bone augmentation procedures in conjunction with particulated porcine xenograft. METHODS: Overall, 8 partially edentulous patients (6 females and 2 males) with a mean age of 45 years requiring bone regeneration procedures to achieve a prosthetically driven implant placement were enrolled. All ridge defects were augmented using a xenogeneic cortical bone barrier in combination with particulated heterologous bone. Bone biopsies were collected during the re-entry procedure. RESULTS: A total of 15 implants were placed both simultaneously or in a staged approach in the augmented sites. No complications occurred during the rehabilitation. Histologically, the bone lamina was widely vascularized and integrated with the surrounding soft tissues and the native bone. The presence of osteoclastic lacunae suggested an active remodelling of the particulated graft and a gradual substitution with the newly formed bone. CONCLUSION: Alveolar reconstruction by means of the collagenated cortical lamina gave promising clinical and histological results. The rigidity and the slow resorption pattern allowed for the blood clot protection even in case of vertical defects, avoiding at the same time the re-entry surgery for its removal. PMID- 27362811 TI - Dental implant positioning by using the root way. A predictable technique for postextractive surgery. AB - BACKGROUND: Postextractive dental implant surgery is a technique characterized by several advantages like placing the implant during the same moment of the extraction, so reducing the time of the surgery and consequently all the prosthetic procedure; however some limitations still remain during this procedure. The disadvantages are represented by the unpredictable results of the healing of the extraction socket, its bone resorption and the dental implant inclination even using a prosthetic guide. Aim of this study is to present a predictable technique for having better aesthetic and functional results during the dental implant positioning. METHODS: This study want to presents clinical and radiological case report of dental implant placed following the line of the root before the extraction, in order to share with the clinicians a surgical experience that results to be simple and predictable. RESULTS: The implants placed with this kind of technique showed successful osseointegration after an uneventful healing period of two years. CONCLUSIONS: The described technique allows the clinician to achieve the ideal implant positioning during immediate implant placement at multirooted extraction sites. PMID- 27362808 TI - miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer. AB - MicroRNAs (miRNAs) have critical roles in regulating cancer cell survival, proliferation and sensitivity to chemotherapy. The potential application of using miRNAs to predict chemotherapeutic response to cancer treatment is highly promising. However, the underlying mechanisms of chemotherapy response control by miRNAs remain to be fully identified and their prognostic value has not been fully evaluated. Here we show a strong correlation between miR-205 expression and chemosensitivtiy to TAC (docetaxol, doxorubicin plus cyclophosphamide), a widely used neoadjuvant chemotherapy (NAC) regimen, for breast cancer patients. High level of miR-205 predicted better response to TAC regimen NAC in breast cancer patients. We found miR-205 downregulated in both MCF-7/A02 and CALDOX cells, two drug-resistant derivatives of MCF-7 and Cal51 cells, and its ectopic expression led to an increase in apoptosis resensitization of both drug-resistant cell lines to doxorubicin and taxol. We further show that miR-205 directly binds VEGFA and FGF2 mRNA 3'-UTRs and confirm that miR-205 levels are negatively correlated with VEGFA and FGF2 mRNA expression in breast cancer patients. Adding VEGFA and FGF2 exogenously to chemosensitive breast cancer cells and chemoresistant cells with miR-205 overexpression led to drug resistance. Consistently, low VEGFA and FGF2 expression correlated with better response to NAC in breast cancer patients. In addition, inhibition of tumor growth and resensitization to doxorubicin were also observed in mouse tumor xenografts from cells overexpressing miR-205. Taken together, our data suggest that miR-205 enhances chemosensitivity of breast cancer cells to TAC chemotherapy by suppressing both VEGFA and FGF2, leading to evasion of apoptosis. MiR-205 may serve as a predictive biomarker and a potential therapeutic target in breast cancer treatment. PMID- 27362812 TI - Orthodontic management of missing lateral incisor by miniscrew-anchored device. AB - Congenitally missing teeth are one of the most common tooth anomalies associated to therapeutic sets of problems. Orthodontists should consider these clinical cases because management often requires an integrated orthodontic and restorative approach. In the present study authors reported a therapy note referred to a 14 year-old male patient affected by missing maxillary lateral incisors, bilateral dental Class II and deep bite, treated in 2009 at the Department of Orthodontics of the University of Messina. An orthodontic treatment has been planned with the aim of distalize maxillary molar and the following opening of the spaces necessary for the prosthetic restoration of missing lateral incisor. For the distalization of maxillary molars has been decided to use a Distal Jet supported by miniscrew (Distal-Screw, American Orthodontics, Sheboygan, WI, USA). After seven months of treatment with distal screw, maxillary molar distalization was completed, obtaining a bilateral molar Class I. A multi-bracket orthodontic appliance was bonded in the upper and lower arch using Empower Brackets (American Orthodontics). Class II molar relationship has been over-corrected to Class I in about seven months. The orientation of the force vector resulted in a tipping and rotation of the first molars, without significant vertical changes. Distal Jet reinforced with screws seems to be effective in molar distalization without any type of side effects. The advantages of this device were the absence of patient compliance, relatively predictable outcomes, favorable esthetics, possibility of different activations in each side. PMID- 27362813 TI - Three-dimensional evaluation of different prosthesis retention systems using finite element analysis and the Von Mises stress test. AB - BACKGROUND: The aim of this paper is to underline the prosthodontics components features of two different overdenture retention systems on dental implants. The use of titanium, dental implants for replacing missing teeth is today considered to be a predictable procedure giving the patients esthetic and function for long time. METHODS: Finite element analysis (FEA) and tests based on the Von Mises criterion have been applied in order to evaluate the stress distribution over two different prosthodontics retention systems. Two models with the ball attachment and with the Locator(r) systems have been created and put on simulated chewing stresses. RESULTS: The two systems were subjected to axial and oblique forces and both guaranteed good results over simulated masticatory cycle. However, the Locator system seemed to better respond to the overall load distributions. CONCLUSIONS: Clinicians should choose the better prosthetic solution for the ridge they want to restore. Both retention systems offer long-term success if applied following the manufacture guide limitations and suggestions. PMID- 27362814 TI - Brief Behavioral Treatment for Insomnia in Persons Living with HIV. AB - This study examined the feasibility and preliminary efficacy of brief behavioral treatment for insomnia (BBTI) for persons living with HIV (PLWH). Of the 22 persons enrolled, 9 were lost before starting treatment, and one dropped out after starting BBTI. Acceptability was rated favorably by those completing the treatment (n = 12). The most common problems pertained to sleep hygiene: variable bedtimes and rise times, watching television, or consuming caffeine. Improvements on sleep outcomes at posttreatment were clinically and statistically significant on questionnaire and sleep diary outcomes. This study supports the overall feasibility of BBTI in PLWH, and the preliminary evidence supports further research on this treatment for PLWH who have insomnia, but dropouts indicate that some individuals may have difficulty initiating treatment. PMID- 27362815 TI - An adaptation for exhaled breath condensate collection in rabbits. AB - AIM: To set up and test the feasibility of a handmade apparatus adapted for exhaled breath condensate (EBC) collection in medium-sized animals. MATERIALS AND METHODS: The apparatus was produced using an 18-mm thick u-shaped borosilicate glass. The u-shaped tube body is 25 cm in diameter, and the horizontal portions are 12 cm in diameter. The base consists of a tube joint 14/20 or 14 mm thick by 20 cm in diameter, and has a length of 5 cm. This has a hole that is plugged for condensate flow to a 1.5 mL polypropylene microtube that stores the condensate during collection. Was placed inside a styrofoam box and immersed in crushed ice and salt to ensure cooling. The temperature was monitored and maintained throughout the collection at -10 degrees C. One of the outputs of the u-shaped tube was connected to the expiratory limb of the ventilator. RESULTS: An experimental model of ALI, induced by oleic acid (OA) was adopted to determine the concentration of biomarkers of oxidative stress: malondialdehyde (MDA), glutathione (GSH), and nitrite/nitrate (NOx). The proposed model allows measurement of NOx, MDA, and GSH. However, the NOx and MDA levels in the EBC were not significant. It was only possible to observe an upward trend, which suggests a temporal evolution of the presence of these markers in the EBC. CONCLUSION: The EBC collection method adapted is effective to generate sufficient content that allows to determine the levels of different biomarkers, such as NOx, MDA, and GSH, that are involved in oxidative and inflammatory stress processes during respiratory diseases. PMID- 27362816 TI - Variation of trace element concentrations in patients undergoing hemodialysis in the north of Spain. AB - BACKGROUND: Trace elements are essential substances for the proper physiological and biochemical functioning of the organism. Hemodialysis patients are potentially at risk of deficiency or excess of these elements. The application of inductively coupled plasma mass spectrometry (ICP-MS) allows the simultaneous quantification of very small amounts of multiple trace elements. The aim was to measure the serum concentration of copper (Cu), zinc (Zn), selenium (Se), and nickel (Ni), and the whole blood concentration of arsenic (As), lead (Pb), and manganese (Mn), in patients undergoing hemodialysis as well as in controls. METHODS: The study was carried out in 57 hemodialysis patients compared with 57 controls with normal renal function. Serum and whole blood samples from the dialysis group were collected before and after hemodialysis sessions and Cu, Zn, Se, Ni, As, Pb and Mn levels were determined using ICP-MS. RESULTS: Hemodialysis patients showed significantly lower blood levels of Cu, Zn and Se than controls (p < 0.001) and higher concentrations of Ni, As and Pb (p < 0.0001). The levels of Mn were similar in both groups. After performing hemodialysis, Cu, Zn, Se and Ni concentrations were significantly higher than the pre-hemodialysis levels (p < 0.0001). However, the concentration of As decreased (p < 0.0001) and Pb and Mn levels were not significantly altered after the dialysis session. CONCLUSION: Hemodialysis patients are at increased risk of trace elements deficiency (especially for Zn and Se) or excess (Ni) in respect to healthy subjects. Monitoring of blood levels and supplementation of some trace elements may be indicated in patients undergoing hemodialysis. PMID- 27362818 TI - [The emergence of behavioral addictions]. PMID- 27362817 TI - Monitoring of intracellular adenosine triphosphate in CD4(+) T cells to predict the occurrence of cytomegalovirus disease in kidney transplant recipients. AB - The measurement of intracellular concentrations of adenosine triphosphate (iATP) in phytohemagglutinin-stimulated CD4(+) T cells constitutes a surrogate marker for post-transplant cell-mediated immunity (CMI). This assay has shown suboptimal accuracy for predicting infection after kidney transplantation (KT). We hypothesize that its predictive capacity depends on the specific contribution of the CMI to host-pathogen interactions. We assessed iATP levels in 100 KT recipients at baseline and months 1, 3, and 6 (363 measurements). No association was found between iATP at month 1 and the risk for overall or bacterial infection, although such association was evident for cytomegalovirus (CMV) disease (multivariate-adjusted hazard ratio [per 50-unit increment]: 0.83; P value = 0.048). There were no significant differences in mean iATP between stable patients (319.4 ng/ml) and those developing overall (304.1 ng/ml) or bacterial infection (346.9 ng/ml) over the 45 days following monitoring. However, iATP was significantly lower in patients who developed CMV disease (223.5 ng/ml; P-values <0.002). The optimal cutoff (265 ng/ml) for predicting CMV disease in patients not receiving antiviral prophylaxis yielded sensitivity, specificity, positive, and negative predictive values of 85.7%, 68.3%, 15.2%, and 98.6%, respectively. In conclusion, a non-pathogen-specific monitoring of CMI by means of iATP informs the risk of CMV disease in KT recipients. PMID- 27362819 TI - [Burnout syndrome. Legal medicine: analysis and evaluation INAIL protection in cases of suicide induced by burnout within the helping professions]. AB - After a survey of the definition and etiopathogenesis of burnout syndrome (BOS) carried out with the support of the most reliable available literature on the subject, the essay focuses on clinical evaluation (psychometric identification and quantification) of burn-out. In accordance with Circular 71/2003 of INAIL, it is assumed to be essential both legally and scientifically knowledge that the syndrome of burnout, knowledge, which involves an analysis of the case conducted with objective strictness and critical sensibility. It is carried out by collecting data on work history, physiological history, remote and proximal pathological history and performing a physical examination including neuro psychiatric and psycho-diagnostic tests surveys. Only after the ascertainment of an effective existence of a psychiatric syndrome related to burnout phenomenon indeed, it will be possible (and necessary) to quantify the period of illness and the potential temporary biological damage or, more rarely, a permanent one. Given the difficulty of applying the forensic methodology to BOS (among which: the evaluation of the previous state of the person, the assessment of the causal link, the difficulties of nosographic of mental illness, the near impossibility of adequate prognostic evaluation, the difficulty to identify suitable criteria for establishing the importance and nature of limitations of daily living), in order to quantify the damage as objective as possible, it will be necessary to: 1) reconstruct the previous mental state of the subject; 2) assess the psychopathological condition following the event which the action of recognition focuses on; 3) express the clinical severity graduation judgment of the framework as well as a prognosis regarding the mental disorder found. The second part of the analysis focuses on the relationship between BOS and "helping profession"; specific attention is paid, in this section of work, to the analysis of the relationship between a typical BOS work-related stress and suicide. PMID- 27362820 TI - [Drug safety warnings in psychiatry: adverse drug reactions' signaling from 2002 to 2014]. AB - OBJECTIVE: Monitoring drug-related side effects in psychiatric patients is highly recommended. In fact, frequent exposure to long-term polipharmacotherapy, poor compliance to pharmachological treatment and comorbidity with organic illnesses requiring the prescription of other drugs are causes of pharmacokinetic/pharmacodynamic interactions. These vulnerability factors result in a certain increase in adverse drug reactions (ADRs). METHODS: This study performes an analysis of Italian Medicine Agency data, in the section "signal analysis", to attempt an assessment of the safety warnings among the different psychotropic drug classes, belonging to the ATC class: N03 (antiepileptics), N05 (antipsychotics), N06 (psycho-analectic drugs). Then we analysed, in a descriptive way, the different association between the drug and the related ADR, evaluating the different safety profiles, in relation to experimental studies, supporting the importance of the signal. RESULTS: In the last years, among the new 25 ADRs, 10 were related to antidepressant drugs (8 SSRI, 1 mirtazapine, 1 agomelatine). In relation to antipsychotic drugs, 6 new correlations were found between drug and ADR onset, mainly among atypical antispychotics. Other correlations (6 above all) were found among antiepileptic drugs. Among benzodiazepines, a signal linked to rabdomylysis onset was found. It is also recommended an evaluation of safety profile in relation to zolpidem prescription. DISCUSSION: The results of our systematic review are a motivational input, considering the continuous increase of safety warnings, to attentively monitor drug's prescription. Spontaneous ADRs' signaling is a classical system to provide the required attention in relation to a potential risk. The clinician in charge must report this because he is the key figure in the drugs' safety process. CONCLUSIONS: In psychiatry, in which a long-term pharmachological therapy is frequent, clinicians are requested to find and signal ADRs to the competent authority. PMID- 27362821 TI - Metacognitive and emotional/motivational executive functions in individuals with autism spectrum disorder and attention deficit hyperactivity disorder: preliminary results. AB - BACKGROUND: Deficits in executive functions (EF) are frequently observed in autism spectrum disorder (ASD) and in attention deficit hyperactivity disorder (ADHD). The aim of this study was to evaluate executive performances of children with ASD and ADHD, and then make between-group comparisons as well as comparisons with a control group. METHODS: A total of 58 subjects were recruited, 17 with ASD but without intellectual impairment, 18 with ADHD-combined presentation and 23 with typical development, matched on gender, chronological age and intellectual level. They were tested on some EF domains, namely planning, mental flexibility, response inhibition and generativity, which account for both metacognitive and emotional/motivational executive functions. Results. Results showed a large overlapping of EF dysfunctions in ASD and ADHD and were not indicative of the presence of two real distinct EF profiles. Nevertheless, in ADHD, a more severe deficit in prepotent response inhibition (emotional/motivational EF) was found. CONCLUSIONS: Results are partially consistent with those found in the literature. Further studies with larger samples are needed to determine how ASD and ADHD differ in terms of their strengths and weaknesses across EF domains. PMID- 27362822 TI - Assessing positive and negative experiences: validation of a new measure of well being in an Italian population. AB - The aim of this study is to explore the psychometric properties of an affect scale, the Scale of Positive and Negative Experience(SPANE), in an Italian speaking population. The results of this study demonstrate that the Italian version of the SPANE has psychometric properties similar to those shown by the original and previous versions, and it presents satisfactory reliability and factorial validity. The results of the Confirmatory Factor Analysis support the expected two-factor structure, positive and negative feeling, which characterized the previous versions. As expected, measures of negative affect, anxiety, negative future expectances, and depression correlated positively with the negative experiences SPANE subscale, and negatively with the positive experiences SPANE subscale. Results of this study demonstrate that the Italian version of the SPANE has psychometric properties similar to those shown by the original and previous versions, and it presents satisfactory reliability and factorial validity. The use of this instrument provides clinically useful information about a person's overall emotional experience and it is an indicator of well-being. Although further studies are required to confirm the psychometric characteristics of the scale, the SPANE Italian version is expected to improve theoretical and empirical research on the well-being of the Italian population. PMID- 27362823 TI - [Critical evaluation of current diagnostic classification systems in psychiatry: the case of DSM-5]. AB - Since its first edition, the Diagnostic and Statistical manual of Mental disorders (DSM) has had a great impact on the scientific community and the public opinion as well. In 2013, the American Psychiatric Association released the fifth edition of the manual and - as for the previous versions - several criticisms raised. In particular, the persistence of the categorical approach to mental disorders represents one of the main debated topics, as well as the introduction of new diagnostic syndromes, which are not based on an adequate evidences. Moreover, the threshold of diagnostic criteria for many mental disorders has been lowered, with the consequence that the boundaries between "normality" and "pathology" is not so clear. In this paper, we will: 1) report the historical development of the DSM from the publication of its first edition; 2) describe the main changes introduced in the DSM-5; 3) discuss critical elements in the DSM-5. The current debate regarding the validity of diagnostic manuals and its criteria is threatening the psychiatric discipline, but a possible solution should be represented by the integration of diagnostic criteria with the in-depth description of patient's psychopathological experiences. PMID- 27362824 TI - [Not Available]. PMID- 27362825 TI - Fractionation of Plant Bioactives from Black Carrots (Daucus carota subspecies sativus varietas atrorubens Alef.) by Adsorptive Membrane Chromatography and Analysis of Their Potential Anti-Diabetic Activity. AB - Black and purple carrots have attracted interest as colored extracts for coloring food due to their high content of anthocyanins. This study aimed to investigate the polyphenol composition of black carrots. Particularly, the identification and quantification of phenolic compounds of the variety Deep Purple carrot (DPC), which presents a very dark color, was performed by HPLC-PDA and HPLC-ESI-MS(n) analyses. The separation of polyphenols from a DPC XAD-7 extract into an anthocyanin fraction (AF) and co-pigment fraction (CF; primarily phenolic acids) was carried out by membrane chromatography. Furthermore, possible anti-diabetic effects of the DPC XAD-7 extract and its AF and CF were determined. DPC samples (XAD-7, CF, and AF) inhibited alpha-amylase and alpha-glucosidase in a dose dependent manner. Moreover, DPC XAD-7 and chlorogenic acid, but not DPC CF and DPC AF, caused a moderate inhibition of intestinal glucose uptake in Caco-2 cells. However, DPC samples did not affect glucagon-like peptide-1 (GLP-1) secretion and dipeptidyl peptidase IV (DPP-4) activity. Overall, DPC exhibits an inhibitory effect on alpha-amylase and alpha-glucosidase activity and on cellular glucose uptake indicating potential anti-diabetic properties. PMID- 27362826 TI - Parameter redundancy in discrete state-space and integrated models. AB - Discrete state-space models are used in ecology to describe the dynamics of wild animal populations, with parameters, such as the probability of survival, being of ecological interest. For a particular parametrization of a model it is not always clear which parameters can be estimated. This inability to estimate all parameters is known as parameter redundancy or a model is described as nonidentifiable. In this paper we develop methods that can be used to detect parameter redundancy in discrete state-space models. An exhaustive summary is a combination of parameters that fully specify a model. To use general methods for detecting parameter redundancy a suitable exhaustive summary is required. This paper proposes two methods for the derivation of an exhaustive summary for discrete state-space models using discrete analogues of methods for continuous state-space models. We also demonstrate that combining multiple data sets, through the use of an integrated population model, may result in a model in which all parameters are estimable, even though models fitted to the separate data sets may be parameter redundant. PMID- 27362827 TI - Chemiluminescence Resonance Energy Transfer Competitive Immunoassay Employing Hapten-Functionalized Quantum Dots for the Detection of Sulfamethazine. AB - We describe a new strategy for using chemiluminescence resonance energy transfer (CRET) by employing hapten-functionalized quantum dots (QDs) in a competitive immunoassay for detection of sulfamethazine (SMZ). Core/multishell QDs were synthesized and modified with phospholipid-PEG. The modified QDs were functionalized with the hapten 4-(4-aminophenyl-sulfonamido)butanoic acid. The CRET-based immunoassay exhibited a limit of detection for SMZ of 9 pg mL(-1), which is >4 orders of magnitude better than a homogeneous fluorescence polarization immunoassay and is 2 orders of magnitude better than a heterogeneous enzyme-linked immunosorbent assay. This strategy represents a simple, reliable, and universal approach for detection of chemical contaminants. PMID- 27362828 TI - Distributive Processing by the Iron(II)/alpha-Ketoglutarate-Dependent Catalytic Domains of the TET Enzymes Is Consistent with Epigenetic Roles for Oxidized 5 Methylcytosine Bases. AB - The ten-eleven translocation (TET) proteins catalyze oxidation of 5 methylcytosine ((5m)C) residues in nucleic acids to 5-hydroxymethylcytosine ((5hm)C), 5-formylcytosine ((5f)C), and 5-carboxycytosine ((5ca)C). These nucleotide bases have been implicated as intermediates on the path to active demethylation, but recent reports have suggested that they might have specific regulatory roles in their own right. In this study, we present kinetic evidence showing that the catalytic domains (CDs) of TET2 and TET1 from mouse and their homologue from Naegleria gruberi, the full-length protein NgTET1, are distributive in both chemical and physical senses, as they carry out successive oxidations of a single (5m)C and multiple (5m)C residues along a polymethylated DNA substrate. We present data showing that the enzyme neither retains (5hm)C/(5f)C intermediates of preceding oxidations nor slides along a DNA substrate (without releasing it) to process an adjacent (5m)C residue. These findings contradict a recent report by Crawford et al. ( J. Am. Chem. Soc. 2016 , 138 , 730 ) claiming that oxidation of (5m)C by CD of mouse TET2 is chemically processive (iterative). We further elaborate that this distributive mechanism is maintained for TETs in two evolutionarily distant homologues and posit that this mode of function allows the introduction of (5m)C forms as epigenetic markers along the DNA. PMID- 27362829 TI - What is the recurrence rate of takotsubo syndrome in patients treated with beta blockers and angiotensin converting enzyme inhibitors/angiotensin receptor blockers? PMID- 27362830 TI - Cardiovascular effects of histone deacetylase inhibitors epigenetic therapies: Systematic review of 62 studies and new hypotheses for future research. PMID- 27362831 TI - Systolic blood pressure and cardiovascular mortality in middle-aged and elderly adults - The Singapore Chinese Health Study. AB - BACKGROUND: While elevated systolic blood pressure (SBP) is related to cardiovascular disease (CVD) mortality, it is unclear if the optimal SBP level may differ by age or the presence of underlying CVD. OBJECTIVE: We investigated the association between SBP categories and CVD mortality among middle-aged and elderly adults with and without CVD history. METHODS: We used data from 30,692 participants of the population-based Singapore Chinese Health Study who had blood pressures measured using a standard protocol at ages 48-85years between 1994 and 2005. Information on lifestyle factors were collected at recruitment (1993-1998) and during follow-up interviews (1999 and 2004). Mortality was identified via nationwide registry linkage up to 31 December 2014. RESULTS: SBP 120-139mmHg category was associated with lowest risk of CVD mortality in both age-groups of <60 and 60+years, as well as in those with and without underlying coronary heart disease or stroke. Overall, compared to this category, CVD risk was non significantly increased in lower SBP categories and significantly increased in the higher SBP categories. The risk estimates associated with elevated SBP were higher among those <60years compared to their older counterparts, but less distinct between those with and without underlying CVD. CONCLUSION: SBP 120 139mmHg was associated with the lowest risk of CVD mortality in middle aged and elderly adults, regardless of underlying CVD. Although risks in both adult groups were similar, there is a greater risk associated with higher SBP among those aged below 60years, highlighting a greater urgency of treatment in this younger group. PMID- 27362832 TI - The incidence of all-cause, cardiovascular and respiratory disease admission among 20,252 users of lisinopril vs. perindopril: A cohort study. AB - BACKGROUND: Major international guidelines do not offer explicit recommendations on any specific angiotensin-converting enzyme inhibitor (ACEI) agent over another within the same drug group. This study compared the effectiveness of lisinopril vs. perindopril in reducing the incidence of hospital admission due to all-cause, cardiovascular disease and respiratory disease. METHODS: Adult patients who received new prescriptions of lisinopril or perindopril from 2001 to 2005 in all public hospitals and clinics in Hong Kong were included, and followed up for >=2years. The incidence of admissions due to all-cause, cardiovascular disease and respiratory disease were evaluated, respectively, by using Cox proportional hazard regression models. The regression models were constructed with propensity score matching to minimize indication biases. RESULTS: A total of 20,252 eligible patients with an average age of 64.5years (standard deviation 15.0) were included. The admission rate at 24months within the date of index prescription due to any cause, cardiovascular disease and respiratory disease among lisinopril vs. perindopril users was 24.8% vs. 24.8%, 13.7% vs. 14.0% and 6.9% vs. 6.3%, respectively. Lisinopril users were significantly more likely to be admitted due to respiratory diseases (adjusted hazard ratios [AHR]=1.25, 95% CI 1.08 to 1.43, p=0.002 at 12months; AHR=1.17, 95% CI 1.04 to 1.31, p=0.009 at 24months) and all causes (AHR=1.12, 95% CI 1.05 to 1.19, p<0.001 at 24months) than perindopril users. CONCLUSIONS: These findings support intra-class differences in the effectiveness of ACEIs, which could be considered by clinical guidelines when the preferred first-line antihypertensive drugs are recommended. PMID- 27362833 TI - Comparison of originator and biosimilar therapeutic monoclonal antibodies using comprehensive two-dimensional liquid chromatography coupled with time-of-flight mass spectrometry. AB - As research, development, and manufacturing of biosimilar protein therapeutics proliferates, there is great interest in the continued development of a portfolio of complementary analytical methods that can be used to efficiently and effectively characterize biosimilar candidate materials relative to the respective reference (i.e., originator) molecule. Liquid phase separation techniques such as liquid chromatography and capillary electrophoresis are powerful tools that can provide both qualitative and quantitative information about similarities and differences between reference and biosimilar materials, especially when coupled with mass spectrometry. However, the inherent complexity of these protein materials challenges even the most modern one-dimensional (1D) separation methods. Two-dimensional (2D) separations present a number of potential advantages over 1D methods, including increased peak capacity, 2D peak patterns that can facilitate unknown identification, and improvement in the compatibility of some separation methods with mass spectrometry. In this study, we demonstrate the use of comprehensive 2D-LC separations involving cation exchange (CEX) and reversed-phase (RP) separations in the first and second dimensions to compare 3 reference/biosimilar pairs of monoclonal antibodies (cetuximab, trastuzumab and infliximab) that cover a range of similarity/disimilarity in a middle-up approach. The second dimension RP separations are coupled to time-of-flight mass spectrometry, which enables direct identification of features in the chromatograms obtained from mAbs digested with the IdeS enzyme, or digestion with IdeS followed by reduction with dithiothreitol. As many as 23 chemically unique mAb fragments were detected in a single sample. Our results demonstrate that these rich datasets enable facile assesment of the degree of similarity between reference and biosimilar materials. PMID- 27362834 TI - Collimator design for spatially-fractionated proton beams for radiobiology research. AB - Preclinical and translational research is an imperative to improve the efficacy of proton radiotherapy. We present a feasible and practical method to produce spatially-modulated proton beams for cellular and small animal research for clinical and research facilities. The University of Washington (UW) 50.5 MeV proton research beamline hosting a brass collimation system was modeled using Monte Carlo simulations. This collimator consisted of an array of 2 cm long slits to cover an area of 2 * 2 cm(2). To evaluate the collimator design effects on dose rate, valley dose and the peak-to-valley dose ratios (PVDR) the following parameters were varied; slit width (0.1-1.0 mm), peak center-to-center distance (1-3 mm), collimator thickness (1-7 cm) and collimator location along the beam axis. Several combinations of slit widths and 1 mm spacing achieved uniform dose at the Bragg peak while maintaining spatial modulation on the beam entrance. A more detailed analysis was carried out for the case of a slit width of 0.3 mm, peak center-to-center distance of 1 mm, a collimator thickness of 5 cm and with the collimator flush against the water phantom. The dose rate at 5 mm depth dropped relative to an open field by a factor of 12 and produced a PVDR of 10.1. Technical realization of proton mini-beams for radiobiology small animal research is demonstrated to be feasible. It is possible to obtain uniform dose at depth while maintaining reasonable modulation at shallower depths near the beam entrance. While collimator design is important the collimator location has a strong influence on the entrance region PVDRs and on dose rate. These findings are being used to manufacture a collimator for installation on the UW cyclotron proton beam nozzle. This collimator will enable comparative studies on the radiobiological efficacy of x-rays and proton beams. PMID- 27362835 TI - Costimulation of soil glycosidase activity and soil respiration by nitrogen addition. AB - Unprecedented levels of nitrogen (N) have been deposited in ecosystems over the past century, which is expected to have cascading effects on microbially mediated soil respiration (SR). Extracellular enzymes play critical roles on the degradation of soil organic matter, and measurements of their activities are potentially useful indicators of SR. The links between soil extracellular enzymatic activities (EEAs) and SR under N addition, however, have not been established. We therefore conducted a meta-analysis from 62 publications to synthesize the responses of soil EEAs and SR to elevated N. Nitrogen addition significantly increased glycosidase activity (GA) by 13.0%, alpha-1,4-glucosidase (AG) by 19.6%, beta-1,4-glucosidase (BG) by 11.1%, beta-1,4-xylosidase (BX) by 21.9% and beta-D-cellobiosidase (CBH) by 12.6%. Increases in GA were more evident for long duration, high rate, organic and mixed N addition (combination of organic and inorganic N addition), as well as for studies from farmland. The response ratios (RRs) of GA were positively correlated with the SR-RRs, even when evaluated individually for AG, BG, BX and CBH. This positive correlation between GA-RR and SR-RR was maintained for most types of vegetation and soil as well as for different methods of N addition. Our results provide the first evidence that GA is linked to SR under N addition over a range of ecosystems and highlight the need for further studies on the response of other soil EEAs to various global change factors and their implications for ecosystem functions. PMID- 27362836 TI - Staged Models for Interdisciplinary Research. AB - Modellers of complex biological or social systems are often faced with an invidious choice: to use simple models with few mechanisms that can be fully analysed, or to construct complicated models that include all the features which are thought relevant. The former ensures rigour, the latter relevance. We discuss a method that combines these two approaches, beginning with a complex model and then modelling the complicated model with simpler models. The resulting "chain" of models ensures some rigour and relevance. We illustrate this process on a complex model of voting intentions, constructing a reduced model which agrees well with the predictions of the full model. Experiments with variations of the simpler model yield additional insights which are hidden by the complexity of the full model. This approach facilitated collaboration between social scientists and physicists-the complex model was specified based on the social science literature, and the simpler model constrained to agree (in core aspects) with the complicated model. PMID- 27362837 TI - The Emergence of Groups and Inequality through Co-Adaptation. AB - The emergence of groups and of inequality is often traced to pre-existing differences, exclusionary practices, or resource accumulation processes, but can the emergence of groups and their differential success simply be a feature of the behaviors of a priori equally-capable actors who have mutually adapted? Using a simple model of behavioral co-adaptation among agents whose individual actions construct a common environment, we present evidence that the formation of unequal groups is endemic to co-adaptive processes that endogenously alter the environment; agents tend to separate into two groups, one whose members stop adapting earliest (the in-group), and another comprising agents who continue to adapt (the out-group). Over a wide range of model parameters, members of the in group are rewarded more on average than members of the out-group. The primary reason is that the in-group is able to have a more profound influence on the environment and mold it to the benefit of its members. This molding capacity proves more beneficial than the persistence of adaptivity, yet, crucially, which agents are able to form a coalition to successfully exert this control is strongly contingent on random aspects of the set of agent behaviors. In this paper, we present the model, relevant definitions, and results. We then discuss its implications for the study of complex adaptive systems generally. PMID- 27362838 TI - The impact of loneliness on paranoia: An experimental approach. AB - BACKGROUND AND OBJECTIVES: Loneliness is a common problem in patients with schizophrenia, and may be particularly linked with persecutory ideation. Nevertheless, its role as a potential risk factor in the formation and maintenance of persecutory delusions is largely unexplored. METHODS: Loneliness was experimentally manipulated using a false-feedback paradigm in a non-clinical sample (n = 60). Change in state paranoia was compared between the induction of increased loneliness, the induction of reduced loneliness and a control condition. Distinct associations between pre-post scores of loneliness and state paranoia were examined at three (medium/high/low) levels of proneness to psychosis across the experimental conditions. RESULTS: Reduction of loneliness was associated with a significant reduction of present paranoid beliefs, while induction of loneliness lead to more pronounced paranoia on trend significance level. Moreover, proneness to psychosis significantly moderated the impact of loneliness on paranoia. Persons with a pronounced level of proneness to psychosis showed a stronger reduction of paranoid beliefs as a consequence of a decrease in loneliness, than less prone individuals. LIMITATIONS: A limitation is the small size of our sample, which may have limited the power to detect significant within group changes in state paranoia in the high-loneliness condition and changes in loneliness in the low-loneliness condition. CONCLUSIONS: The findings support the feasibility of the experimental design to manipulate loneliness and suggest that loneliness could be a cause of paranoia. However, the findings need to be confirmed in high risk samples to draw conclusions about the role of loneliness in the genesis of clinically relevant levels of paranoia and derive implications for cognitive behaviour therapy. PMID- 27362839 TI - Population Structure, Abundance and Movement of Whale Sharks in the Arabian Gulf and the Gulf of Oman. AB - Data on the occurrence of whale sharks, Rhincodon typus, in the Arabian Gulf and Gulf of Oman were collected by dedicated boat surveys and via a public-sightings scheme during the period from 2011 to 2014. A total of 422 individual whale sharks were photo-identified from the Arabian Gulf and the northern Gulf of Oman during that period. The majority of sharks (81%, n = 341) were encountered at the Al Shaheen area of Qatar, 90 km off the coast, with the Musandam region of Oman a secondary area of interest. At Al Shaheen, there were significantly more male sharks (n = 171) than females (n = 78; X2 = 17.52, P < 0.05). Mean estimated total length (TL) for sharks was 6.90 m +/- 1.24 (median = 7 m; n = 296). Males (7.25 m +/- 1.34; median = 8 m, n = 171) were larger than females (6.44 m +/ 1.09; median = 7 m, n = 78; Mann-Whitney U test, p < 0.01). Of the male sharks assessed for maturity 63% were mature (n = 81), with 50% attaining maturity by 7.29 m and 100% by 9.00 m. Two female sharks of >9 m individuals were visually assessed as pregnant. Connectivity among sharks sighted in Qatari, Omani and UAE waters was confirmed by individual spot pattern matches. A total of 13 identified sharks were re-sighted at locations other than that at which they were first sighted, including movements into and out of the Arabian Gulf through the Strait of Hormuz. Maximum likelihood techniques were used to model an estimated combined population for the Arabian Gulf and Gulf of Oman of 2837 sharks +/- 1243.91 S.E. (95% C.I. 1720-6295). The Al Shaheen aggregation is thus the first site described as being dominated by mature males while the free-swimming pregnant females are the first reported from the Indian Ocean. PMID- 27362840 TI - Stereochemical Consequences of Vinylpyruvate Hydratase-Catalyzed Reactions. AB - A stereochemical analysis has been carried out on two vinylpyruvate hydratases (VPH), which convert 2-hydroxy-2,4-pentadienoate to 2-keto-4S-hydroxypentanoate in meta-fission pathways. Bacterial strains with this pathway can use aromatic compounds as sole sources of energy and carbon. The analysis was carried out using the 5-methyl and 5-chloro derivatives of 2-hydroxy-2,4-pentadienoate with the enzymes from Pseudomonas putida mt-2 (Pp) and Leptothrix cholodnii SP-6 (Lc). In both organisms, VPH is in a complex with the preceding enzyme in the pathway, 4-oxalocrotonate decarboxylase (4-OD). In D2O, a deuteron is incorporated stereospecifically at the C-3 and C-5 positions of product by both Pp and Lc enzymes. Accordingly, the complexes generate (3S,5S)-3,5-[di-D]-2-keto-4S hydroxyhexanoate and (3S,5R)-3,5-[di-D]-2-keto-4R-hydroxy-5-chloropentanoate (4R and 5R due to a priority numbering change). The substitution at C-5 (CH3 or Cl) or the source of the enzyme (Pp or Lc) does not change the stereochemical outcome. One mechanism that can account for the results is the ketonization of the 5-substituted dienol to the alpha,beta-unsaturated ketone (placing a deuteron at C-5 in D2O), followed by the conjugate addition of water (placing a deuteron at C-3). The stereochemical outcome for VPH (from Pp and Lc) is the same as that reported for a related enzyme, 2-oxo-hept-4-ene-1,7-dioate hydratase, from Escherichia coli C. The combined observations suggest similar mechanisms for these three enzymes that could possibly be common to this group of enzymes. PMID- 27362841 TI - Early Clinical Experience with a Polymer-Free Biolimus A9 Drug-Coated Stent in DES-Type Patients Who Are Poor Candidates for Prolonged Dual Anti-Platelet Therapy. AB - INTRODUCTION: Prolonged dual anti-platelet therapy (DAPT) may cause excess bleeding in certain patients. The biolimus-A9 drug-coated stent (BA9-DCS) has a rapid drug-elution profile allowing shortened DAPT. Data were gathered on the early experience implanting this stent in drug-eluting stent eligible patients deemed to be at high risk of bleeding. BACKGROUND AND METHODS: The demographics, procedural data and clinical outcomes were gathered prospectively for 249 patients treated with a BA9-DCS stent at 2 UK centres, and compared to a cohort of patients treated in the same period with drug-eluting stents (PCI-DES). RESULTS: Operator-defined BA9-DCS indications included warfarin therapy, age, and anaemia. Patients receiving a BA9-DCS were older (71.6+/-11.8 vs. 64.8+/-11.6yrs, p<0.001), more often female (38.2 vs. 26.8%, P<0.001), and more likely to have comorbidity including chronic kidney disease or poor LV function than PCI-DES patients. The baseline Mehran bleed risk score was also significantly higher in the BA9-DCS group (19.4+/-8.7 vs. 13.1+/-5.8, p<0.001). Of the BA9-DCS cohort, 95.5% of patients demonstrated disease fitting NICE criteria for DES placement. The number of lesions treated (1.81+/-1.1 vs. 1.58+/-0.92, p = 0.003), total lesion length (32.1+/-21.7 vs. 26.1+/-17.6mm, p<0.001), number of stents used (1.93+/-1.11 vs. 1.65+/-1.4, p = 0.007) and total stent length (37.5+/-20.8 vs. 32.4+/-20.3, p<0.01) were greater for BA9-DCS patients. DAPT was prescribed for 3.3+/-3.9 months for BA9-DCS patients and 11.3+/-2.4 months for PCI-DES patients (p<0.001). At follow up of 392+/-124 days despite the abbreviated DAPT course stent related event were infrequent with ischemia-driven restenosis PCI (2.8 vs. 3.4%, p = 0.838), and stent thrombosis (1.6 vs. 2.1%, p = 0.265) rates similar between the BA9-DCS ad PCI-DES groups. After propensity scoring all clinical end points were similar between both cohorts. CONCLUSIONS: This early experience using polymer-free BA9 drug-coated stents in drug-eluting stent type patients at risk of bleeding are encouraging. Further studies are warranted. PMID- 27362843 TI - Association between Ultrasound Features and the 21-Gene Recurrence Score Assays in Patients with Oestrogen Receptor-Positive, HER2-Negative, Invasive Breast Cancer. AB - A multigene expression assay corresponds to the likelihood of breast cancer recurrence after the initial diagnosis and can be used to guide the decision for additional chemotherapy. However, only few studies have investigated the associations between the imaging features of breast cancer and the results of multigene expression assays. Our study was to identify the relationship between imaging features on ultrasound (US) and the recurrence score (RS) on a 21-gene expression assay in patients with oestrogen receptor (ER)-positive, HER2-negative breast cancer. 267 patients with ER-positive, HER-negative invasive breast cancer who underwent examinations using US and Oncotype DX assay were included. US images were independently reviewed by dedicated breast radiologists who were blind to the RS. Tumour roundness was measured using a laboratory-developed software program. The pathological data were reviewed, including immunohistochemistry results. Univariate analysis was performed to assess the associations between the RS and each variable. Multiple logistic regression analysis was used to identify independent predictors of high RS. Of 267 patients, 147 (55%) had low, 96 (36%) intermediate, and 24 (9%) had high RS. According to the univariate analysis, parallel orientation, presence of calcification in the mass, and tumour roundness were positively associated with high RS. Multiple logistic regression analysis showed that parallel orientation (OR = 5.53) and tumour roundness (OR = 1.70 per 10 increase) were associated with high RS. Parallel orientation and tumour roundness are independent variables that may predict high RS in patients with ER-positive, HER2-negative breast cancer. PMID- 27362844 TI - 25-Hydroxyvitamin D and Parathyroid Hormone Levels Are Independently Associated with the Hemoglobin A1c Level of Korean Type 2 Diabetic Patients: The Dong-Gu Study. AB - In type 2 diabetic patients, the relationships between 25-hydroxyvitamin D and parathyroid hormone levels, and glycemic control, remain unclear. We evaluated associations between 25-hydroxyvitamin D, parathyroid hormone, and hemoglobin A1c levels after adjusting for other covariates, including log transformed 25 hydroxyvitamin D levels and log transformed parathyroid hormone levels, in Korean patients with type 2 diabetes. In total, 1,175 patients with type 2 diabetes were selected from 8,857 individuals who completed the baseline survey of the Dong-gu study, conducted in Korea from 2007 to 2010. After adjusting for other covariates, we found that the mean hemoglobin A1c level was inversely associated with the 25-hydroxyvitamin D level (Q1: 7.47% [7.30-7.63], Q2: 7.25% [7.09-7.40], Q3: 7.17% [7.02-7.32], Q4: 7.19% [7.02-7.35]; p for trend = 0.021, p for between groups = 0.050) and the parathyroid hormone level (Q1: 7.35% [7.19-7.51], Q2: 7.34% [7.19-7.50], Q3: 7.28% [7.13-7.43], Q4: 7.09% [6.94-7.24]; p for trend = 0.022, p for between groups = 0.048). However, the mean fasting glucose level was not associated with either the 25-hydroxyvitamin D or parathyroid hormone level. In conclusion, inverse associations were evident between hemoglobin A1c, 25 hydroxyvitamin D and parathyroid hormone levels in Korean patients with type 2 diabetes. The associations remained significant after adjusting for other covariates, including the log transformed 25-hydroxyvitamin D levels and log transformed parathyroid hormone levels. PMID- 27362846 TI - HIV and HCV Co-Culture Promotes Profibrogenic Gene Expression through an Epimorphin-Mediated ERK Signaling Pathway in Hepatic Stellate Cells. AB - Accelerated fibrosis in patients co-infected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) has been a major cause of mortality in the highly active anti-retroviral therapy (HAART) era. However, the role of co infection in accelerating the progression of liver fibrosis, particularly with regard to the effects of co-infection on hepatic stellate cells (HSCs), remains unclear. We hypothesized that HIV and HCV induce liver fibrosis synergistically by altering the regulation of epimorphin production, and thereby indirectly alter HSC function. Here, we examined the effects of epimorphin on HSC proliferation and invasion, and the changes in fibrogenesis-related gene activity in HSCs (LX2) in the presence of inactivated CXCR4-tropic HIV and HCV (JFH1). The combination of HIV and HCV significantly increased epimorphin expression, which increased the proliferation and invasion capabilities of HSCs. Epimorphin also induced the expression of profibrogenic tissue inhibitor of metalloproteinase 1 (TIMP1) in an extracellular signal-regulated kinase (ERK)-dependent manner. These data indicated that the effects of HIV/HCV co-infection on hepatic fibrosis might be mediated in part by EPM. Strategies to limit the expression of EPM might represent a novel therapeutic approach to prevent the progression of hepatic fibrosis during HIV/HCV co-infection. PMID- 27362845 TI - Preliminary differences in resting state MEG functional connectivity pre- and post-ketamine in major depressive disorder. AB - Functional neuroimaging techniques including magnetoencephalography (MEG) have demonstrated that the brain is organized into networks displaying correlated activity. Group connectivity differences between healthy controls and participants with major depressive disorder (MDD) can be detected using temporal independent components analysis (ICA) on beta-bandpass filtered Hilbert envelope MEG data. However, the response of these networks to treatment is unknown. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, exerts rapid antidepressant effects. We obtained MEG recordings before and after open-label infusion of 0.5mg/kg ketamine in MDD subjects (N=13) and examined networks previously shown to differ between healthy individuals and those with MDD. Connectivity between the amygdala and an insulo-temporal component decreased post ketamine in MDD subjects towards that observed in control subjects at baseline. Decreased baseline connectivity of the subgenual anterior cingulate cortex (sgACC) with a bilateral precentral network had previously been observed in MDD compared to healthy controls, and the change in connectivity post-ketamine was proportional to the change in sgACC glucose metabolism in a subset (N=8) of subjects receiving [11F]FDG-PET imaging. Ketamine appeared to reduce connectivity, regardless of whether connectivity was abnormally high or low compared to controls at baseline. These preliminary findings suggest that sgACC connectivity may be directly related to glutamate levels. PMID- 27362847 TI - Two-dimensional blue native/SDS-PAGE analysis of whole cell lysate protein complexes of rice in response to salt stress. AB - To understand the biology of a plant in response to stress, insight into protein protein interactions, which almost define cell behavior, is thought to be crucial. Here, we provide a comparative complexomics analysis of leaf whole cell lysate of two rice genotypes with contrasting responses to salt using two dimensional blue native/SDS-PAGE (2D-BN/SDS-PAGE). We aimed to identify changes in subunit composition and stoichiometry of protein complexes elicited by salt. Using mild detergent for protein complex solubilization, we were able to identify 9 protein assemblies as hetero-oligomeric and 30 as homo-oligomeric complexes. A total of 20 proteins were identified as monomers in the 2D-BN/SDS-PAGE gels. In addition to identifying known protein complexes that confirm the technical validity of our analysis, we were also able to discover novel protein-protein interactions. Interestingly, an interaction was detected for glycolytic enzymes enolase (ENO1) and triosephosphate isomerase (TPI) and also for a chlorophyll a-b binding protein and RuBisCo small subunit. To show changes in subunit composition and stoichiometry of protein assemblies during salt stress, the differential abundance of interacting proteins was compared between salt-treated and control plants. A detailed exploration of some of the protein complexes provided novel insight into the function, composition, stoichiometry and dynamics of known and previously uncharacterized protein complexes in response to salt stress. PMID- 27362848 TI - Evidence of an Exponential Decay Pattern of the Hepatitis Delta Virus Evolution Rate and Fluctuations in Quasispecies Complexity in Long-Term Studies of Chronic Delta Infection. AB - Chronic HDV infection can cause a severe form of viral hepatitis for which there is no specific treatment. Characterization of the hepatitis B or C viral quasispecies has provided insight into treatment failure and disease recurrence following liver transplantation, has proven useful to understand hepatitis B e antigen seroconversion, and has helped to predict whether hepatitis C infection will resolve or become chronic. It is likely that characterization of the hepatitis delta virus (HDV) quasispecies will ultimately have similar value for the management of this infection. This study sought to determine the RNA evolution rates in serum of chronic hepatitis delta (CHD) treatment-naive patients, using next-generation sequencing methods. The region selected for study encompassed nucleotide positions 910 to 1270 of the genome and included the amber/W codon. Amber/W is a substrate of the editing process by the ADAR1 host enzyme and is essential for encoding the 2 delta antigens (HDAg). The amber codon encodes the small (unedited) HDAg form and the W codon the large (edited) HDAg form. The evolution rate was analyzed taking into account the time elapsed between samples, the percentage of unedited and edited genomes, and the complexity of the viral population. The longitudinal studies included 29 sequential samples from CHD patients followed up for a mean of 11.5 years. In total, 121,116 sequences were analyzed. The HDV evolution rate ranged from 9.5x10 3 to 1.2x10-3 substitutions/site/year and showed a negative correlation with the time elapsed between samples (p<0.05). An accumulation of transition-type changes was found to be responsible for higher evolution rates. The percentages of unedited and edited genomes and the quasispecies complexity showed no relationships with the evolution rate, but the fluctuations in the percentages of genomes and in complexity suggest continuous adaptation of HDV to the host conditions. PMID- 27362849 TI - Sevoflurane Therapy for Severe Refractory Bronchospasm in Children. AB - OBJECTIVES: To describe the effect of inhaled sevoflurane in the treatment of severe refractory bronchospasm in children. DESIGN: Retrospective case series. SETTING: Two PICUs of tertiary general university hospitals in Spain. PATIENTS: Ten patients ranging from 5 months to 14 years old with severe bronchospasm and acute respiratory failure requiring tracheal intubation and mechanical ventilation and treated with sevoflurane from 2008 to 2015. INTERVENTION: Inhaled sevoflurane therapy was initiated after failure of conventional medical management and mechanical ventilation. In two patients, sevoflurane was administered through a Servo 900C ventilator (Maquet, Bridgewater, NJ) equipped with a vaporizer and in the other eight patients via the Anesthetic Conserving Device (AnaConDa; Sedana medical, Uppsala, Sweden) with a critical care ventilator. MEASUREMENTS AND MAIN RESULTS: Inhaled sevoflurane resulted in statistically significant decreases of PaCO2 of 34.2 torr (95% CI, 8.3-60), peak inspiratory pressure of 14.3 cm H2O (95% CI, 8.6-19.9), and improvement in pH of 0.17 (0.346-0.002) within 6 hours of administration. Only one patient presented hypotension responsive to volume administration at the beginning of the treatment. All patients could be extubated within a median time of 120 hours (interquartile range, 46-216). CONCLUSIONS: Inhaled sevoflurane therapy decreases the levels of PaCO2 and peak inspiratory pressure values, and it may be considered as a rescue therapy in patients with life-threatening bronchospasm refractory to conventional therapy. PMID- 27362850 TI - Epidemiology of Sepsis in Children Admitted to PICUs in South America. AB - OBJECTIVES: To report the prevalence of sepsis within the first 24 hours at admission and the PICU sepsis-related mortality among critically ill children admitted to PICU in South America. DESIGN: A prospective multicenter cohort study. SETTING: Twenty-one PICU, located in five South America countries. PATIENTS: All children from 29 days to 17 years old admitted to the participating PICU between June 2011 and September 2011. Clinical, demographic, and laboratory data were registered within the first 24 hours at admission. Outcomes were registered upon PICU discharge or death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 1,090 patients included in this study, 464 had sepsis. The prevalence of sepsis, severe sepsis, and septic shock were 42.6%, 25.9%, and 19.8%, respectively. The median age of sepsis patients was 11.6 months (interquartile range, 3.2-48.7) and 43% had one or more prior chronic condition. The prevalence of sepsis was higher in infants (50.4%) and lower in adolescents (1.9%). Sepsis-related mortality was 14.2% and was consistently higher with increased disease severity: 4.4% for sepsis, 12.3% for severe sepsis, and 23.1% for septic shock. Twenty-five percent of deaths occurred within the first 24 hours at PICU admission. Multivariate analysis showed that higher Pediatric Risk of Mortality and Pediatric Logistic Organ Dysfunction scores, the presence of two or more chronic conditions, and admission from pediatric wards were independently associated with death. CONCLUSIONS: We observed high prevalence of sepsis and sepsis-related mortality among this sample of children admitted to PICU in South America. Mortality was associated with greater severity of illness at admission and potentially associated with late PICU referral. PMID- 27362851 TI - Decreasing IV Potassium in Pediatric Cardiac Intensive Care: Quality Improvement Project. AB - OBJECTIVES: IV potassium supplementation is commonly used in the pediatric cardiovascular ICU. However, concentrated IV potassium chloride doses can lead to life-threatening complications. We report results of a quality improvement project aimed at decreasing concentrated IV potassium chloride exposure. DESIGN: Retrospective evaluation of a quality improvement project aimed at reducing IV potassium chloride exposure. SETTING: Pediatric cardiac ICU. PATIENTS: All patients admitted to pediatric cardiac ICUs in April 2013 to September 2013 (preprotocol) and October 2013 to April 2014 (postprotocol). INTERVENTIONS: A quality improvement team developed a potassium protocol aimed at maintaining serum potassium levels 3.0-5.5 mEq/L, via algorithm focused on early enteral supplementation. All patients receiving IV diuretics who had a serum potassium level less than 4.5 mEq/L and urine output more than 0.5 mL/kg/hr had protocol initiated with potassium chloride-containing IV fluids or enteral potassium chloride. Concentrated IV potassium chloride infusions were limited to asymptomatic patients with serum potassium less than 2.0 mEq/L and high-risk patients at less than 3.0 mEq/L. Serum potassium levels were measured once daily, and protocolized adjustments were made based on this level and concurrent diuretic therapy. MEASUREMENTS AND MAIN RESULTS: Serum potassium, potassium chloride supplementation, patient cost, fluid administration, and arrhythmia incidence were compared pre and post protocol. Four hundred forty-three admissions were included (234 pre protocol and 209 post protocol). No significant differences were found in demographics. There was no difference in mean morning serum potassium after protocol implementation (3.85 [0.77] mEq/L before protocol and 3.89 [0.75] mEq/L after protocol; p = 0.90). Concentrated IV potassium chloride administration was decreased by 86% (331 vs 47 doses). With protocol, there was decreased incidence in days with one measured episode of hyperkalemia (11 vs 4/1,000 patient-days; p = 0.02) and a trend toward decreased hypokalemia (433 vs 400/1,000 patient-days; p = 0.05). Arrhythmia incidence was similar (p = 0.59). CONCLUSIONS: Protocolized potassium management in pediatric cardiac intensive care patients decreased concentrated IV potassium chloride exposure and incidence of hyperkalemia. Lower potassium treatment threshold for IV potassium chloride was not associated with increased arrhythmias. PMID- 27362852 TI - Remote Ischemic Preconditioning in the PICU: A Simple Concept With a Complex Past. AB - OBJECTIVE: In this study, we will review the most recently proposed mechanisms for remote ischemic preconditioning and summarize the past 10 years of clinical studies, as well as potential reasons for why, despite over 20 years of research on remote ischemic preconditioning, it is not routinely used in the pediatric critical care patient. In addition, future directions for remote ischemic preconditioning research will be discussed. DATA SOURCES: We searched the PubMed database for relevant literature. STUDY SELECTION AND DATA EXTRACTION: In PubMed, the search terms "ischemic preconditioning" and "remote preconditioning" were used. Randomized controlled trials published from 2006 until the present time that used a blood pressure cuff to induce remote ischemic preconditioning were included. We also reviewed the reference lists of the articles found in the PubMed search and included those thought to contribute to the objectives. All studies pertaining to remote ischemic preconditioning that included pediatric patients were reviewed. DATA SYNTHESIS AND CONCLUSIONS: Differences in study outcomes in the effect of remote ischemic preconditioning on organ protection have been reported and may have played a large role in limiting the translation of findings into routine clinical practice. Ongoing efforts to protocolize the remote ischemic preconditioning technique in large multicenter trials with clearly delineated patient risk groups, including the use of biomarkers for enrichment, may help to ultimately determine if this procedure can be safely and effectively used for critically ill children. PMID- 27362853 TI - Factors Associated With Continuous Low-Dose Heparin Infusion for Central Venous Catheter Patency in Critically Ill Children Worldwide. AB - OBJECTIVES: To identify patient, hospital, and central venous catheter factors that may influence the use of low-dose heparin infusion for central venous catheter patency in critically ill children. DESIGN: Secondary analysis of an international multicenter observational study. SETTING: Fifty-nine PICUs over four study dates in 2012, involving seven countries. PATIENTS: Children less than 18 years old with a central venous catheter who were admitted to a participating unit and enrolled in the completed Prophylaxis against Thrombosis Practice study were included. All overflow patients were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 2,484 patients in the Prophylaxis against Thrombosis Practice study, 1,312 patients had a central venous catheter. Five hundred seven of those patients used low-dose heparin infusion. The frequency of low-dose heparin infusion was compared across various patient, hospital, and central venous catheter factors using chi-square, Mann-Whitney U, and Fisher exact tests. In the multivariate analysis, age was not a significant factor for low-dose heparin infusion use. Patients with pulmonary hypertension had decreased low-dose heparin infusion use, whereas those with active surgical or trauma diagnoses had increased low-dose heparin infusion use. All centrally inserted central venous catheters were more likely to use low-dose heparin infusion when compared with peripherally inserted central venous catheters. The Asia-Pacific region showed increased low-dose heparin infusion use, along with community hospitals and smaller ICUs (< 10 beds). CONCLUSIONS: Patient, central venous catheter, and hospital factors are associated with the use of low-dose heparin infusion in critically ill children. Further study is needed to evaluate the efficacy and persistence of low-dose heparin infusion use. PMID- 27362854 TI - Burden and Outcomes of Severe Pertussis Infection in Critically Ill Infants. AB - OBJECTIVES: Despite World Health Organization endorsed immunization schedules, Bordetella pertussis continues to cause severe infections, predominantly in infants. There is a lack of data on the frequency and outcome of severe pertussis infections in infants requiring ICU admission. We aimed to describe admission rates, severity, mortality, and costs of pertussis infections in critically ill infants. DESIGN: Binational observational multicenter study. SETTING: Ten PICUs and 19 general ICUs in Australia and New Zealand contributing to the Australian and New Zealand Paediatric Intensive Care Registry. PATIENTS: Infants below 1 year of age, requiring intensive care due to pertussis infection in Australia and New Zealand between 2002 and 2014. MEASUREMENTS AND MAIN RESULTS: During the study period, 416 of 42,958 (1.0%) infants admitted to the ICU were diagnosed with pertussis. The estimated population-based ICU admission rate due to pertussis ranged from 2.1/100,000 infants to 18.6/100,000 infants. Admission rates were the highest among infants less than 60 days old (p < 0.0001). Two hundred six infants (49.5%) required mechanical ventilation, including 20 (4.8%) treated with high-frequency oscillatory ventilation, 16 (3.8%) with inhaled nitric oxide, and 7 (1.7%) with extracorporeal membrane oxygenation. Twenty of the 416 children (4.8%) died. The need for mechanical ventilation, high-frequency oscillatory ventilation, nitric oxide, and extracorporeal membrane oxygenation were significantly associated with mortality (p < 0.01). Direct severe pertussis related hospitalization costs were in excess of USD$1,000,000 per year. CONCLUSIONS: Pertussis continues to cause significant morbidity and mortality in infants, in particular during the first months of life. Improved strategies are required to reduce the significant healthcare costs and disease burden of this vaccine-preventable disease. PMID- 27362856 TI - Temporal Trends of Respiratory Syncytial Virus-Associated Hospital and ICU Admissions Across the United States. AB - OBJECTIVES: To describe the regionality and seasonality of respiratory syncytial virus-associated hospital and ICU admissions for 10 consecutive years using a national database. DESIGN: Post hoc analysis of data from an existing national database, Pediatric Health Information System. We modeled the adjusted odds of hospital and ICU admissions for varied seasons (fall, winter, spring, and summer) and regions (Northeast, South, Midwest, and West) using a mixed-effects logistic regression model after adjusting for several patient and center characteristics. SETTING: Forty-two children's hospitals across the Unites States. PATIENTS: Patients 1 day through 24 months old with inpatient admission (ward and/or ICU) for respiratory syncytial virus- associated infection at a Pediatric Health Information System-participating hospital were included (2004-2013). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1,937,994 inpatient admissions during the study period, 146,357 children were admitted for respiratory syncytial virus-associated acute respiratory illness. Of these inpatient admissions, 32,470 children(22%) were admitted to ICU during their hospital stay. Overall adjusted odds of respiratory syncytial virus-associated hospital and ICU admissions in recent years (2010-2013) were higher than previous years (2004-2006 and 2007-2009). In recent years, respiratory syncytial virus associated hospital and ICU admissions have increased in winter and spring seasons. Regionally in recent years, the overall adjusted odds of both respiratory syncytial virus-associated hospital and ICU admissions have increased in the South and West regions. CONCLUSIONS: Wide variations in regional and seasonal patterns in hospital and ICU admissions were noted in children with respiratory syncytial virus-associated acute respiratory illness across the United States. Results from our study help us better understand the seasonality and regionality of respiratory syncytial virus infection in the United States with the goal to decrease the financial impact on our already stressed healthcare system by being better prepared for respiratory syncytial virus season. PMID- 27362857 TI - Isolated Coronary Artery Fistula in Fetal Heart: Case Reports and Literature Review. AB - We report two cases of prenatally diagnosed isolated coronary artery fistula. The first fetus had a fistulous communication between the left circumflex coronary artery and the right atrium. The second fetus had right coronary artery to left ventricle fistula. In addition, we have also reviewed previously published reports on prenatally diagnosed coronary artery fistulae, focusing on their clinical profiles, outcome and postnatal treatment. PMID- 27362858 TI - Genetic Risk Evaluation in Wet Age-Related Macular Degeneration Treatment Response. AB - OBJECTIVE: To evaluate the pharmacogenetic relationship between CFH haplotypes and single nucleotide polymorphisms (SNPs) with response to ranibizumab treatment for neovascular age-related macular degeneration (nAMD). PATIENTS AND METHODS: This was a prospective cohort study involving 70 treatment-naive nAMD patients. Patients were genotyped for CFH haplotypes and SNPs in the C3, ARMS2, and mtDNA genes. Visual acuity and central macular thickness were assessed at baseline and during 6 monthly follow-up visits. Multivariate logistic regression was used to determine the association between genotypes and a gain of >=15 letters at the 6 month endpoint after adjusting for potential confounders. RESULTS: CFH haplotypes were associated with a gain of >=15 letters at the 6-month endpoint (p = 0.046). Patients expressing protective haplotypes were more likely to achieve a gain of >=15 letters relative to the greatly increased risk haplotypes [OR 6.58 (95% CI: 1.37, 31.59)]. CONCLUSION: CFH is implicated in nAMD patient treatment response to ranibizumab. PMID- 27362859 TI - Expert Opinion to Identify High-Risk Entry Routes of Canine Rabies into Papua New Guinea. AB - The proximity of Papua New Guinea (PNG) to canine rabies-endemic countries in South-East Asia presents a risk of incursion of this disease into PNG and the rest of the Oceanic region. The objective of this study was to identify the highest risk routes for entry of dogs - associated with movement of people - into PNG from canine rabies-endemic countries. A structured, in-country expert elicitation workshop was used, and 20 entry routes were identified. The highest risk routes were three land routes from Papua, Indonesia (hunters, traditional border crossers and unregulated, unchecked 'shopper-crossers') and two sea routes (fishing and logging). These results will be used to direct more detailed risk assessments to develop surveillance strategies and incursion response plans. PMID- 27362860 TI - Assessment of Membrane Fluidity Fluctuations during Cellular Development Reveals Time and Cell Type Specificity. AB - Cell membrane is made up of a complex structure of lipids and proteins that diffuse laterally giving rise to what we call membrane fluidity. During cellular development, such as differentiation cell membranes undergo dramatic fluidity changes induced by proteins such as ARC and Cofilin among others. In this study we used the generalized polarization (GP) property of fluorescent probe Laurdan using two-photon microscopy to determine membrane fluidity as a function of time and for various cell lines. A low GP value corresponds to a higher fluidity and a higher GP value is associated with a more rigid membrane. Four different cell lines were monitored such as hN2, NIH3T3, HEK293 and L6 cells. Membrane fluidity was measured at 12h, 72h and 92 h. Our results show significant changes in membrane fluidity among all cell types at different time points. GP values tend to increase significantly within 92 h in hN2 cells and 72 h in NIH3T3 cells and only at 92 h in HEK293 cells. L6 showed a marked decrease in membrane fluidity at 72 h and starts to increase at 92 h. As expected, NIH3T3 cells have more rigid membrane at earlier time points. On the other hand, neurons tend to have the highest membrane fluidity at early time points emphasizing its correlation with plasticity and the need for this malleability during differentiation. This study sheds light on the involvement of membrane fluidity during neuronal differentiation and development of other cell lines. PMID- 27362862 TI - Detection and Classification of Measurement Errors in Bioimpedance Spectroscopy. AB - Bioimpedance spectroscopy (BIS) measurement errors may be caused by parasitic stray capacitance, impedance mismatch, cross-talking or their very likely combination. An accurate detection and identification is of extreme importance for further analysis because in some cases and for some applications, certain measurement artifacts can be corrected, minimized or even avoided. In this paper we present a robust method to detect the presence of measurement artifacts and identify what kind of measurement error is present in BIS measurements. The method is based on supervised machine learning and uses a novel set of generalist features for measurement characterization in different immittance planes. Experimental validation has been carried out using a database of complex spectra BIS measurements obtained from different BIS applications and containing six different types of errors, as well as error-free measurements. The method obtained a low classification error (0.33%) and has shown good generalization. Since both the features and the classification schema are relatively simple, the implementation of this pre-processing task in the current hardware of bioimpedance spectrometers is possible. PMID- 27362863 TI - Influence of Ta substitution for Nb in Zn3Nb2O8 and the impact on the crystal structure and microwave dielectric properties. AB - Zn3(Nb1-xTax)2O8 (x = 0.02-0.10) ceramics were prepared via a solid-state reaction route and the dependence of their microwave dielectric properties on their structural characteristics were investigated. XRD patterns show that a single Zn3Nb2O8 phase with layered crystal structures was formed in ceramic samples with 0.02 <=x<= 0.10. The Raman spectrum was used for the first time to analyze the vibrational phonon modes of the Zn3Nb2O8 samples. Based on P-V-L dielectric theory, the intrinsic factors that influence the microwave dielectric properties were systematically investigated. According to the calculated results, the experimental dielectric constant had a close relationship with the theoretical dielectric constant. The Nb-site lattice energy was found to be a vital factor in explaining the change of the Q*f values. While the Nb-site bond energy increases, the |tauf| value decreases which indicates that higher bond energy would result in a more stable system. This work presents a novel method to investigate the intrinsic factors that influence microwave dielectric properties. PMID- 27362861 TI - Proteomic Analysis of Vitreous Humor in Retinal Vein Occlusion. AB - PURPOSE: To analyze the protein profile of human vitreous of untreated patients with retinal vein occlusion (RVO). METHODS: Sixty-eight vitreous humor (VH) samples (44 from patients with treatment naive RVO, 24 controls with idiopathic floaters) were analyzed in this clinical-experimental study using capillary electrophoresis coupled to mass spectrometer and tandem mass spectrometry. To define potential candidate protein markers of RVO, proteomic analysis was performed on RVO patients (n = 30) and compared with controls (n = 16). To determine validity of potential biomarker candidates in RVO, receiver operating characteristic (ROC) was performed by using proteome data of independent RVO (n = 14) and control samples (n = 8). RESULTS: Ninety-four different proteins (736 tryptic peptides) could be identified. Sixteen proteins were found to be significant when comparing RVO and control samples (P = 1.43E-05 to 4.48E-02). Five proteins (Clusterin, Complement C3, Ig lambda-like polypeptide 5 (IGLL5), Opticin and Vitronectin), remained significant after using correction for multiple testing. These five proteins were also detected significant when comparing subgroups of RVO (central RVO, hemi-central RVO, branch RVO) to controls. Using independent samples ROC-Area under the curve was determined proving the validity of the results: Clusterin 0.884, Complement C3 0.955, IGLL5 1.000, Opticin 0.741, Vitronectin 0.786. In addition, validation through ELISA measurements was performed. CONCLUSION: The results of the study reveal that the proteomic composition of VH differed significantly between the patients with RVO and the controls. The proteins identified may serve as potential biomarkers for pathogenesis induced by RVO. PMID- 27362864 TI - Advances in the diagnosis and classification of systemic lupus erythematosus. AB - INTRODUCTION: Systemic lupus erythematosus (SLE) is the prototype of systemic autoimmune diseases. Patients with SLE display a wide spectrum of clinical and serological findings that can mislead and delay the diagnosis. Diagnostic criteria have not been developed yet, whereas several sets of classification criteria are available; however, none of them has 100% sensitivity and 100% specificity, i.e. the hallmark of diagnostic criteria. Nevertheless, classification criteria are often misused as diagnostic criteria, which may affect earliness of diagnosis and lead to more misdiagnosed cases. Areas covered: In this review, we compare old and new classification criteria, discussing their application and pinpointing their limitations in the management of patients. Moreover, we will focus on current and novel biomarkers for SLE diagnosis, highlighting their predictive value and applicability in clinical practice. Expert commentary: SLE diagnosis still represents a challenge, remaining largely based on a clinical judgment. Besides SLE diagnosis, even its classification is still challenging to date. Indeed, although classification of SLE seems to be achieved more frequently with the 2012 SLICC criteria than with the previous 1997 ACR criteria, this last-updated 2012 set might be improved. Notably, diagnostic and classification criteria should be applied to any subject in the world, and consequently they should include immunological variables validated in different populations, which is still an unmet need. PMID- 27362865 TI - Correction: Neuronal Hyperactivity Disturbs ATP Microgradients, Impairs Microglial Motility, and Reduces Phagocytic Receptor Expression Triggering Apoptosis/Microglial Phagocytosis Uncoupling. AB - [This corrects the article DOI: 10.1371/journal.pbio.1002466.]. PMID- 27362866 TI - Radical Addition of Hydrazones by alpha-Bromo Ketones To Prepare 1,3,5 Trisubstituted Pyrazoles via Visible Light Catalysis. AB - A novel efficient tandem reaction of hydrazones and alpha-bromo ketones is reported for the preparation of 1,3,5-trisubstituted pyrazoles by visible light catalysis. In this system, the monosubstituted hydrazones show wonderful reaction activity with alkyl radicals, generated from alpha-bromo ketones. A radical addition followed by intramolecular cyclization affords the important pyrazole skeleton in good to excellent yields. This efficient strategy under mild conditions with wide group tolerance provides a potential approach to the 1,3,5 trisubstituted pyrazoles. PMID- 27362867 TI - Portal Catheter Fracture in a Pediatric Patient. PMID- 27362855 TI - Targeted Temperature Management After Pediatric Cardiac Arrest Due To Drowning: Outcomes and Complications. AB - OBJECTIVE: To describe outcomes and complications in the drowning subgroup from the Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-of-Hospital trial. DESIGN: Exploratory post hoc cohort analysis. SETTING: Twenty-four PICUs. PATIENTS: Pediatric drowning cases. INTERVENTIONS: Therapeutic hypothermia versus therapeutic normothermia. MEASUREMENTS AND MAIN RESULTS: An exploratory study of pediatric drowning from the Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-of-Hospital trial was conducted. Comatose patients aged more than 2 days and less than 18 years were randomized up to 6 hours following return-of circulation to hypothermia (n = 46) or normothermia (n = 28). Outcomes assessed included 12-month survival with a Vineland Adaptive Behavior Scale score of greater than or equal to 70, 1-year survival rate, change in Vineland Adaptive Behavior Scale-II score from prearrest to 12 months, and select safety measures. Seventy-four drowning cases were randomized. In patients with prearrest Vineland Adaptive Behavior Scale-II greater than or equal to 70 (n = 65), there was no difference in 12-month survival with Vineland Adaptive Behavior Scale-II score of greater than or equal to 70 between hypothermia and normothermia groups (29% vs 17%; relative risk, 1.74; 95% CI, 0.61-4.95; p = 0.27). Among all evaluable patients (n = 68), the Vineland Adaptive Behavior Scale-II score change from baseline to 12 months did not differ (p = 0.46), and 1-year survival was similar (49% hypothermia vs 42%, normothermia; relative risk, 1.16; 95% CI, 0.68-1.99; p = 0.58). Hypothermia was associated with a higher prevalence of positive bacterial culture (any blood, urine, or respiratory sample; 67% vs 43%; p = 0.04); however, the rate per 100 days at risk did not differ (11.1 vs 8.4; p = 0.46). Cumulative incidence of blood product use, serious arrhythmias, and 28-day mortality were not different. Among patients with cardiopulmonary resuscitation durations more than 30 minutes or epinephrine doses greater than 4, none had favorable Pediatric Cerebral Performance Category outcomes (<= 3). CONCLUSIONS: In comatose survivors of out-of-hospital pediatric cardiac arrest due to drowning, hypothermia did not result in a statistically significant benefit in survival with good functional outcome or mortality at 1 year, as compared with normothermia. High risk of culture-proven bacterial infection was observed in both groups. PMID- 27362871 TI - Good News: But Why Is the Incidence of Postoperative Ischemic Optic Neuropathy Falling? PMID- 27362869 TI - Preoperative Falls and Their Association with Functional Dependence and Quality of Life. AB - BACKGROUND: No study has rigorously explored the characteristics of surgical patients with recent preoperative falls. Our objective was to describe the essential features of preoperative falls and determine whether they are associated with preoperative functional dependence and poor quality of life. METHODS: This was an observational study involving 15,060 surveys from adult patients undergoing elective surgery. The surveys were collected between January 2014 and August 2015, with a response rate of 92%. RESULTS: In the 6 months before surgery, 26% (99% CI, 25 to 27%) of patients fell at least once, and 12% (99% CI, 11 to 13%) fell at least twice. The proportion of patients who fell was highest among patients presenting for neurosurgery (41%; 99% CI, 36 to 45%). At least one fall-related injury occurred in 58% (99% CI, 56 to 60%) of those who fell. Falls were common in all age groups, but surprisingly, they did not increase monotonically with age. Middle-aged patients (45 to 64 yr) had the highest proportion of fallers (28%), recurrent fallers (13%), and severe fall related injuries (27%) compared to younger (18 to 44 yr) and older (65+ yr) patients (P < 0.001 for each). A fall within 6 months was independently associated with preoperative functional dependence (odds ratio, 1.94; 99% CI, 1.68 to 2.24) and poor physical quality of life (odds ratio, 2.18; 99% CI, 1.88 to 2.52). CONCLUSIONS: Preoperative falls might be common and are possibly often injurious in the presurgical population, across all ages. A history of falls could enhance the assessment of preoperative functional dependence and quality of life. PMID- 27362870 TI - Perioperative Visual Loss in Spine Fusion Surgery: Ischemic Optic Neuropathy in the United States from 1998 to 2012 in the Nationwide Inpatient Sample. AB - BACKGROUND: Perioperative ischemic optic neuropathy (ION) causes visual loss in spinal fusion. Previous case-control studies are limited by study size and lack of a random sample. The purpose of this study was to study trends in ION incidence in spinal fusion and risk factors in a large nationwide administrative hospital database. METHODS: In the Nationwide Inpatient Sample for 1998 to 2012, procedure codes for posterior thoracic, lumbar, or sacral spine fusion and diagnostic codes for ION were identified. ION was studied over five 3-yr periods (1998 to 2000, 2001 to 2003, 2004 to 2006, 2007 to 2009, and 2010 to 2012). National estimates were obtained using trend weights in a statistical survey procedure. Univariate and Poisson logistic regression assessed trends and risk factors. RESULTS: The nationally estimated volume of thoracic, lumbar, and sacral spinal fusion from 1998 to 2012 was 2,511,073. ION was estimated to develop in 257 patients (1.02/10,000). The incidence rate ratio (IRR) for ION significantly decreased between 1998 and 2012 (IRR, 0.72 per 3 yr; 95% CI, 0.58 to 0.88; P = 0.002). There was no significant change in the incidence of retinal artery occlusion. Factors significantly associated with ION were age (IRR, 1.24 per 10 yr of age; 95% CI, 1.05 to 1.45; P = 0.009), transfusion (IRR, 2.72; 95% CI, 1.38 to 5.37; P = 0.004), and obesity (IRR, 2.49; 95% CI, 1.09 to 5.66; P = 0.030). Female sex was protective (IRR, 0.30; 95% CI, 0.16 to 0.56; P = 0.0002). CONCLUSIONS: Perioperative ION in spinal fusion significantly decreased from 1998 to 2012 by about 2.7-fold. Aging, male sex, transfusion, and obesity significantly increased the risk. PMID- 27362872 TI - Longitudinal measurement equivalence of subjective language brokering experiences scale in Mexican American adolescents. AB - OBJECTIVE: Language brokering occurs frequently in immigrant families and can have significant implications for the well-being of family members involved. The present study aimed to develop and validate a measure that can be used to assess multiple dimensions of subjective language brokering experiences among Mexican American adolescents. METHOD: Participants were 557 adolescent language brokers (54.2% female, Mage.wave1 = 12.96, SD = .94) in Mexican American families. RESULTS: Using exploratory and confirmatory factor analyses, we were able to identify 7 reliable subscales of language brokering: linguistic benefits, socioemotional benefits, efficacy, positive parent-child relationships, parental dependence, negative feelings, and centrality. Tests of factorial invariance show that these subscales demonstrate, at minimum, partial strict invariance across time and across experiences of translating for mothers and fathers, and in most cases, also across adolescent gender, nativity, and translation frequency. Thus, in general, the means of the subscales and the relations among the subscales with other variables can be compared across these different occasions and groups. Tests of criterion-related validity demonstrated that these subscales correlated, concurrently and longitudinally, with parental warmth and hostility, parent-child alienation, adolescent family obligation, depressive symptoms, resilience, and life meaning. CONCLUSION: This reliable and valid subjective language brokering experiences scale will be helpful for gaining a better understanding of adolescents' language brokering experiences with their mothers and fathers, and how such experiences may influence their development. (PsycINFO Database Record PMID- 27362873 TI - Playing up and playing down cultural identity: Introducing cultural influence and cultural variability. AB - OBJECTIVES: Cultural variability (CV) is introduced as an overlooked dimension of cultural identity development pertaining to emphasizing and de-emphasizing the influence of a single cultural identity (i.e., cultural influence [CI]) on daily interactions and behaviors. The Cultural IDentity Influence Measure (CIDIM) is introduced as a novel measure of CI and CV, and hypothesis-driven validation is conducted in two samples along with exploration of associations between CV and well-being. METHOD: A multicultural sample of 242 emerging adults participated in a daily diary study (Mage = 19.95 years, SDage = 1.40) by completing up to eight daily online surveys containing the CIDIM, criterion measures (ethnic identity, other group orientation, ethnic identity salience and daily variability in salience, social desirability), and measures of personal and interpersonal well being. A second validation sample (n = 245) completed a 1-time survey with the CIDIM and a subset of criterion measures. RESULTS: Results using both samples show evidence of CI and CV and demonstrate the validity, reliability, and domain sensitivity of the CIDIM. Further, CV made unique and positive contributions to predicting interaction quality after accounting for ethnic salience and variability in ethnic salience. An analytic approach utilizing standard deviations produced near-identical results to multilevel modeling and is recommended for parsimony. CONCLUSIONS: Ethnic minority and majority individuals make daily adjustments to play up and play down the influence of cultural identity on their social interactions and behaviors, and these adjustments predict interpersonal well-being. Cultural influence and cultural variability contribute to our emerging understanding of cultural identity as dynamic and agentic. (PsycINFO Database Record PMID- 27362874 TI - Assessing accident phobia in mild traumatic brain injury: The Accident Fear Questionnaire. AB - PURPOSE: Despite a documented prevalence of accident phobia in almost 40% of motor vehicle accident (MVA) survivors, the onset of accident phobia after traumatic brain injury (TBI) remains poorly understood. There is currently a body of knowledge about posttraumatic stress disorder (PTSD) in patients with TBI, but less is known about accident phobia following TBI, particularly in cases of mild TBI (mTBI). Accident phobia can impede safe return to driving or motor vehicle travel, inhibiting return to daily functioning. In addition, pain complaints have been found to correlate positively with postinjury anxiety disorders. METHOD: The present study sought to determine the reliability and validity of the Accident Fear Questionnaire (AFQ), a measure used to assess accident phobia, in 72 patients with mTBI using secondary data analysis and the subsequent development of accident phobia postinjury. Furthermore, we sought to examine the impact of pain, anxiety, and depression complaints on the AFQ. RESULTS: Results reveal convergent validity and reliability in mTBI populations. Additionally, pain, anxiety, and depression measures were significantly correlated with scores on the AFQ. CONCLUSIONS: Psychometrically, the phobia avoidance subscale of the AFQ is a reliable measure for use with mTBI populations, although some limitations were found. In particular, the accident profile (AP) subscale was not found to be reliable or valid and could be eliminated from the AFQ. Collectively, the present study contributes to the small body of published literature evaluating accident phobia in patients with mTBI and the impact of pain on the development of postinjury anxiety disorders. (PsycINFO Database Record PMID- 27362875 TI - Resistance to levothyroxine in a bariatric surgery patient: an indication for liquid formulation? AB - We report the case of a 49-year-old female patient with hypothyroidism who underwent bariatric surgery and developed severe hypothyroidism despite high doses of oral levothyroxine (L-T4) tablets. Initially, a high-dose L-T4 tablets absorption test was performed to exclude pseudo-malabsorption. In view of a modest increase in serum T4 levels, L-T4 liquid formulation absorption test was performed, and showed faster and more efficient absorption of thyroid hormones. We discuss the issue of distinguishing malabsorption from pseudo-malabsorption, review the literature concerning the benefits of liquid L-T4 in cases of impaired absorption such as bariatric surgery and consider the socio-economic implications of different liquid formulations. PMID- 27362876 TI - Targeting the Translesion Synthesis Pathway for the Development of Anti-Cancer Chemotherapeutics. AB - Human cells possess tightly controlled mechanisms to rescue DNA replication following DNA damage caused by environmental and endogenous carcinogens using a set of low-fidelity translesion synthesis (TLS) DNA polymerases. These polymerases can copy over replication blocking DNA lesions while temporarily leaving them unrepaired, preventing cell death at the expense of increasing mutation rates and contributing to the onset and progression of cancer. In addition, TLS has been implicated as a major cellular mechanism promoting acquired resistance to genotoxic chemotherapy. Owing to its central role in mutagenesis and cell survival after DNA damage, inhibition of the TLS pathway has emerged as a potential target for the development of anticancer agents. This review will recap our current understanding of the structure and regulation of DNA polymerase complexes that mediate TLS and describe how this knowledge is beginning to translate into the development of small molecule TLS inhibitors. PMID- 27362877 TI - Corneal Crosslinking With Rose Bengal and Green Light: Efficacy and Safety Evaluation. AB - PURPOSE: To evaluate crosslinking of cornea in vivo using green light activation of Rose Bengal (RGX) and assess potential damaging effects of the green light on retina and iris. METHODS: Corneas of Dutch belted rabbits were de-epithelialized, then stained with Rose Bengal and exposed to green light, or not further treated. Corneal stiffness was measured by uniaxial tensiometry. Re-epithelialization was assessed by fluorescein fluorescence. Keratocytes were counted on hematoxylin and eosin (H&E)-stained sections, and iris cell damage was assessed by lactate dehydrogenase staining. Thermal effects on the blood-retinal barrier (BRB) were assessed by fluorescein angiography and those on photoreceptors, retinal pigment epithelium (RPE), and choriocapillaris by light microscopy and transmission electron microscopy. RESULTS: RGX (10-min irradiation; 150 J/cm) increased corneal stiffness 1.9-fold on day 1 (1.25 +/- 0.21 vs. 2.38 +/- 0.59 N/mm; P = 0.036) and 2.8-fold compared with controls on day 28 (1.70 +/- 0.74 vs. 4.95 +/- 1.86 N/mm; P = 0.003). Keratocytes decreased only in the anterior stroma on day 1 (24.0 +/- 3.0 vs. 3.67 +/- 4.73, P = 0.003) and recovered by day 28 (37.7 +/- 8.9 vs. 34.5 +/- 2.4, P = 0.51). Iris cells were not thermally damaged. No evidence of BRB breakdown was detected on days 1 or 28. Retina from RGX-treated eyes seemed normal with RPE cells showing intact nuclei shielded apically by melanosomes, morphologically intact photoreceptor outer segments, normal outer nuclear layer thickness, and choriocapillaris containing intact erythrocytes. CONCLUSIONS: The substantial corneal stiffening produced by RGX together with the lack of significant effects on keratocytes and no evidence for retina or iris damage suggest that RGX-initiated corneal crosslinking may be a safe, rapid, and effective treatment. PMID- 27362878 TI - Urgent Therapeutic Grafting of Platelet-Rich Fibrin Membrane in Descemetocele. AB - PURPOSE: To report the clinical and histopathological results of a novel autologous scaffold grafting, platelet-rich fibrin (PRF) membrane, in cases with descemetocele. METHODS: Three patients with severe corneal stromal melting and central descemetocele caused by neurotrophic keratopathy and infective keratitis underwent PRF membrane grafting on the central cornea for the prevention of imminent corneal perforation. After a quiescent 3-month period, penetrating keratoplasty and cataract extraction were performed for visual rehabilitation in 1 patient and host corneal tissue was examined histopathologically. RESULTS: Pain was significantly relieved, conjunctival inflammation was markedly resolved, and the central descemetocele area became thicker with scar formation in all patients. Histopathological examination revealed fibrosis formation over the descemetocele area without any tissue gap. Newly formed tissue containing irregular corneal lamellae covered the fibrosis formation and accounted for the prevention of perforation. CONCLUSIONS: Temporary PRF membrane grafting may be an alternative intervention to avoid impending corneal perforation in cases with severe descemetocele. PMID- 27362879 TI - Corneal Higher-Order Aberrations in Herpes Simplex Keratitis. AB - PURPOSE: To evaluate corneal higher-order aberrations (HOAs) in eyes with corneal scars due to herpes simplex keratitis (HSK). METHODS: Forty-four eyes of 41 consecutive patients who were diagnosed with corneal scars due to HSK and 18 control eyes were included. HOAs of the anterior and posterior surfaces and the total cornea were analyzed using anterior segment optical coherence tomography. Corneal opacity grades were assigned on the basis of slit-lamp examinations. RESULTS: HOAs within a 4-mm diameter were significantly larger in eyes with HSK (anterior surface, 1.01 +/- 1.18 MUm; posterior surface, 0.25 +/- 0.24; total cornea, 1.00 +/- 1.00) compared with controls (0.10 +/- 0.02, 0.02 +/- 0.00, and 0.09 +/- 0.01, respectively; all P < 0.001). HOAs within a 6-mm diameter were significantly larger in eyes with HSK (anterior surface, 1.87 +/- 1.75; posterior surface, 0.42 +/- 0.44; total cornea, 1.85 +/- 1.46) compared with controls (0.19 +/- 0.04, 0.06 +/- 0.01, and 0.17 +/- 0.03, respectively; all, P < 0.001). The logarithm of the minimum angle of resolution (logMAR) decreased with the corneal opacity score (0.42 +/- 0.61 in grade 1, 1.30 +/- 0.96 in grade 2, and 1.58 +/- 0.90 in grade 3). LogMAR was significantly correlated with HOAs (R = 0.65, P < 0.0001). HOAs of the posterior surface increased from 0.15 +/- 0.15 in grade 1 to 0.37 +/- 0.33 in grade 3 (P = 0.005), whereas there was no difference in HOAs of the anterior surface and the total cornea among the different corneal opacity grades. CONCLUSIONS: Increased HOAs of the anterior and posterior surfaces occur in eyes with corneal opacity due to HSK. Larger corneal HOAs are associated with poorer visual acuity. PMID- 27362880 TI - Determining Factors for Fast Corneal Sensitivity Recovery After Pterygium Excision. AB - PURPOSE: To establish determining factors for fast corneal sensitivity (CS) recovery after pterygium excision. METHODS: Thirty-two eyes of 14 males and 18 females with primary nasal pterygium were recruited. Differences in CS (in the 4 quadrants and the center using a Cochet-Bonnet esthesiometer), pterygium corneal area (PCA), tear osmolarity, tear break-up time, Schirmer test, and ocular symptoms were analyzed before and 1 month after lesion excision. The relationship between CS recovery (difference between the 2 time points; CS1 - CS0) and the other features was assessed. RESULTS: All the studied locations exhibited normal (6 cm) or near-normal mean CS at the 2 time points, except a tendency for moderate hypoesthesia in nasal CS0 (median 4.5; range: 1.5-6.0 cm). Point by point comparison revealed significant postoperative improvements in nasal location (P = 0.008; Wilcoxon signed-rank test) with normal values in 17 eyes (53%) and a median CS1 = 5.0 cm (2.5-5.5 cm) in 15 eyes with no complete recovery. No significant correlation was found between CS0 and the studied variables, and CS1 was only significantly correlated with PCA (rho: -0.441; P < 0.05). CS recovery also showed significant correlation with PCA (rho = -0.516; P < 0.01). CONCLUSIONS: CS recovery after pterygium excision showed important variability, and the only studied factor that seems to be determinant could be PCA. It would be advisable to operate when the lesion is relatively small, with lower surgical injury and faster and complete recovery, thus protecting ocular surface homeostasis. PMID- 27362881 TI - Concurrent Acute Retinal Necrosis in a Patient With Iridocorneal Endothelial Syndrome. AB - PURPOSE: To report a rare case of concurrent acute retinal necrosis in a patient with iridocorneal endothelial syndrome (ICE). METHODS: Case report. RESULTS: A 42 year-old woman showed acute diminution of vision in the right eye. Her fundus examination revealed features of acute retinal necrosis. She had also experienced gradual diminution of vision in her left eye for 5 years. The examination of her left eye revealed corneal edema with mild corectopia and increased intraocular pressure with abnormal endothelium on specular microscopy pointing to a diagnosis of ICE. CONCLUSIONS: This is a rare case where concurrent acute retinal necrosis and ICE syndrome are present in the same patient, possibly pointing to a common viral etiology causing both entities. PMID- 27362882 TI - Existence of Normal Limbal Epithelium in Eyes With Clinical Signs of Total Limbal Stem Cell Deficiency. AB - PURPOSE: To report the presence of normal limbal epithelium detected by in vivo confocal laser scanning microscopy (IVCM) in 3 cases of clinically diagnosed total limbal stem cell deficiency (LSCD). METHODS: This is a retrospective case report consisting of 3 patients who were diagnosed with total LSCD based on clinical examination and/or impression cytology. Clinical data including ocular history, presentation, slit-lamp examination, IVCM, and impression cytology were reviewed. RESULTS: The etiology was chemical burn in 3 cases. One patient had 2 failed penetrating keratoplasties. Another had allogeneic keratolimbal transplantation, but the graft failed 1 year after surgery. The third patient had failed amniotic membrane transplantation. These 3 patients presented with signs of total LSCD including the absence of normal Vogt palisades, complete superficial vascularization of the peripheral cornea, nonhealing epithelial defects, and corneal scarring. Impression cytology was performed in 2 cases to confirm the presence of goblet cells. However, each patient still had distinct areas of corneal and/or limbal epithelial cells detected by IVCM. CONCLUSIONS: Residual normal limbal epithelial cells could be present in eyes with clinical features of total LSCD. IVCM seems to be a more accurate method to evaluate the degree of LSCD. PMID- 27362883 TI - Apparent Corneal Ectasia After Bilateral Intrastromal Femtosecond Laser Treatment for Presbyopia. AB - PURPOSE: To report a case of apparent corneal ectasia after intrastromal femtosecond laser treatment for presbyopia (INTRACOR). METHODS: A healthy 56-year old male with low hyperopia underwent an unremarkable bilateral INTRACOR procedure in March/April 2011. The patient was discharged after follow-up and returned 5 years later. RESULTS: Before discharge, the monocular logarithm of the minimal angle of resolution uncorrected distance visual acuity (UDVA) values were R, 0.0 and L, 0.10. In both eyes near (UNVA) visual acuities were 0.0. There were signs of slight posterior central corneal steepening without loss of corneal stability. Five years postop, monocular UDVA and UNVA values were 0.4 and 0.0, respectively. Ectasia was observed in both eyes, and the centrally placed 5 concentric rings after the INTRACOR procedure were visible under slit-lamp biomicroscopy. CONCLUSIONS: There is no clear reason to explain why the patient developed bilateral corneal steepening. It could be that the patient's corneal stromal fibers gradually weakened over this 5-year period. PMID- 27362884 TI - Successful Treatment Strategies in Granulomatosis With Polyangiitis-Associated Peripheral Ulcerative Keratitis. AB - PURPOSE: Management of granulomatosis with polyangiitis (GPA)-associated peripheral ulcerative keratitis (PUK) is challenging and lacks definite guidelines. We aimed to summarize our treatment and outcome experience with patients with GPA-PUK. METHODS: The Massachusetts Eye Research and Surgery Institution patient database was searched from 2005 to 2015 to identify patients with diagnosis of PUK who suffered from GPA. Individual patient histories were examined, and treatment strategies and outcomes were summarized. RESULTS: There were 16 patients who started treatment with a mean duration follow-up of 64 months (range: 12-110 mo). Rituximab and cyclophosphamide, either alone or in combination with other agents, were the most successful agents in controlling inflammation. Rituximab was administered in 11 patients with remission being achieved in all. Cyclophosphamide successfully controlled inflammation in 50% (5/10). Two of the patients (2/5, 40%) who had achieved initial control on cyclophosphamide had flares of their PUK. Two of 11 (18%) patients on rituximab had flares of scleritis and orbital inflammation but not PUK. Two patients, one in each treatment group, stopped treatment after achieving remission after 6 months of therapy but suffered disease recurrence within 2 months of treatment cessation. CONCLUSIONS: Rituximab achieved a high rate of disease control in PUK patients with GPA and is the preferred agent in halting disease progression. PMID- 27362885 TI - Donor Tissue Preparation for Bowman Layer Transplantation. AB - PURPOSE: To describe and compare 2 preparation techniques for Bowman layer (BL) grafts for use in BL transplantation. METHODS: A retrospective evaluation of the 2 methods for preparing BL grafts was performed, that is, BL graft preparation from donor globes not eligible for penetrating keratoplasty or endothelial keratoplasty (technique I, n = 36) and BL graft preparation from previously excised corneoscleral buttons (technique II, n = 36) that could not be used for PK or had been denuded of Descemet membrane and endothelium for Descemet membrane endothelial keratoplasty graft preparation. BL graft preparation difficulties were recorded, and the preparation failure rate was examined and compared between the techniques. RESULTS: Overall, BL graft preparation was successful in 51 cases (51/72; 70.8%), of which 25 preparations were successful using technique I, and 26 using technique II, representing a success rate of 69.4% (25/36) and 72.2% (26/36) for techniques I and II, respectively. Reasons for discarding a BL graft were tearing of the BL tissue during the preparation (n = 19) and stroma attached to the graft (n = 2). CONCLUSIONS: Isolated BL grafts can be prepared from both whole donor globes and corneoscleral rims with equivalent success. Preparation from corneoscleral rims may offer the advantage that, from one donor cornea, the posterior layers can be used for Descemet membrane endothelial keratoplasty graft preparation and the anterior part for BL graft preparation. PMID- 27362886 TI - Emerging minimally invasive procedures for focal treatment of organ-confined prostate cancer. AB - Prostate cancer is the most common malignancy amongst American men. However, the majority of prostate cancer diagnoses are of low risk, organ-confined disease. Many men elect to undergo definitive treatment, but may benefit from focal therapy to maintain continence and potency. This review reports the mechanism of action and outcomes of emerging focal therapies for prostate cancer. We report the mechanism of action of focal cryotherapy, high intensity focused ultrasound, focal laser ablation, and irreversible electroporation. In addition, we reviewed the largest studies available reporting rates of urinary incontinence, erectile dysfunction, biochemical recurrence-free survival (ASTRO), and post-operative adverse events for each procedure. Each treatment modality stated has a unique mechanism in the ablation of cancerous cells. Genito-urinary symptoms following these studies report incontinence and erectile dysfunction rates ranging from 0 15% and 0-53%, respectively. Biochemical disease-free survival was reported using the ASTRO definition. Some treatment modalities lack the necessary follow-up to determine effectiveness in cancer control. No focal therapy studies reported serious adverse events. These minimally invasive procedures are feasible in a clinical setting and show promising functional and disease control results with short to medium-term follow-up. However, each treatment requires additional robust prospective studies as well as its own unique domain to determine biochemical recurrence free survival to properly determine their role in treatment of organ-confined prostate cancer. PMID- 27362887 TI - Functional characterization of selective exosite-binding inhibitors of matrix metalloproteinase-13 (MMP-13) - experimental validation in human breast and colon cancer. AB - Considering the pathological significance of MMP-13 in breast and colon cancers, exosite-based inhibition of the C-terminal hemopexin (Hpx) domain could serve as an alternative strategy to develop selective inhibitors for MMP-13.Two of six lead compounds, compound 5 (2,3-dihydro-1,4-benzodioxine-5-carboxylic acid) and compound 6 (1-acetyl-4-hydroxypyrrolidine-2-carboxylic acid) exhibited considerable inhibitory activity against MMP-13. Complementing to this study, we have also shown the gene expression levels of MMP-13 within the subtypes of colon and breast cancers classified from patients' tissue samples to provide a better understanding on which subtype of breast cancer patients would get benefited by MMP-13 inhibitors.Our current results show that compounds 5 and 6 could effectively inhibit MMP-13 and provide specific therapeutic possibilities in the treatment of inflammatory disorders and cancers. The characterization of these lead compounds would provide a better mechanistic understanding of exosite-based inhibition of MMP-13, which could overcome the challenges in the identification of other MMP catalytic domain-specific inhibitors. PMID- 27362888 TI - Microstructure of a granular amorphous silica ceramic synthesized by spark plasma sintering. AB - We study the microstructure of a granular amorphous silica ceramic material synthesized by spark plasma sintering. Using monodisperse spherical silica particles as precursor, spark plasma sintering yields a dense granular material with distinct granule boundaries. We use selective etching to obtain nanoscopic pores along the granule borders. We interrogate this highly interesting material structure by combining scanning electron microscopy, X-ray computed nanotomography and simulations based on random close packed spherical particles. We determine the degree of anisotropy caused by the uni-axial force applied during sintering, and our analysis shows that our synthesis method provides a means to avoid significant granule growth and to fabricate a material with well controlled microstructure. PMID- 27362889 TI - Screening of indeno[1,2-b]indoloquinones by MALDI-MS: a new set of potential CDC25 phosphatase inhibitors brought to light. AB - Quinones and quinones-like compounds are potential candidates for the inhibition of CDC25 phosphatases. The combination of MALDI-MS analyses and biological studies was used to develop a rapid screening of a targeted library of indeno[1,2 b]indoloquinone derivatives. The screening protocol using MALDI-TOFMS and MALDI FTICRMS highlighted four new promising candidates. Biological investigations showed that only compounds 5c-f inhibited CDC25A and -C phosphatases, with IC50 values around the micromolar range. The direct use of a screening method based on MALDI-MS technology allowed achieving fast scaffold identification of a new class of potent inhibitors of CDC25 phosphatases. These four molecules appeared as novel molecules of a new class of CDC25 inhibitors. Assessment of 5c-e in an MRC5 proliferation assay provided an early indicator of toxicity to mammalian cells. Compound 5d seems the most promising hit for developing new CDC25 inhibitors. PMID- 27362890 TI - Baseline Ability Makes a Larger Contribution to Race Performance in High-School Sprinters Than Race Experience or Training Exposure. AB - PURPOSE: There has long been a debate regarding the importance of talent versus training in athletic performance. In this study we sought to quantify their relative contributions to the race performance of high-school sprinters. METHODS: Using race results from the athletic.net website, we identified high-school athletes who participated in at least one race in both 9th and 12th grade in the 100 m, 200 m or 400 m. Athletes with a record of racing before high school were excluded from the analyses. Using separate linear regression models for each event and gender, we analyzed the effect of baseline ability, race experience and training exposure on race time in the 12th grade. RESULTS: 35,909 athletes, running a total of 1,627,652 races, contributed to the final analyses. The proportion of variance (R2) in 12th grade race times accounted for by baseline ability ranged from 40% to 51% depending on the event, and was consistently higher for females than males. Race experience explained 3.6-4.4% of the variance and training exposure explained 0.8-1.7%. CONCLUSION: Although race experience and training exposure impact high-school sprinters' performance, baseline ability is the dominant influence. PMID- 27362891 TI - New Antitumor-Active Azole-Bridged Dinuclear Platinum(II) Complexes: Synthesis, Characterization, Crystal Structures, and Cytotoxic Studies. PMID- 27362893 TI - A Survey of Practicing Sleep Coaches. AB - BACKGROUND: Sleep coaches are individuals of various backgrounds who offer services to families struggling with behavioral childhood sleep problems. We conducted a survey of coaches to further elucidate scope of practice, practice patterns, geographic distribution, education, training, and beliefs regarding qualification requirements. METHODS: A Web-based survey was completed by 142 individuals who identified as a sleep coach. RESULTS: Coaches were distributed across 17 countries and 5 continents. Overall, 65% of coaches served clients in countries beyond their home country. Within the United States, coaches were generally located in more affluent and well-educated zip codes near large metropolitan centers, 91% served clients beyond their home state, and 56% served clients internationally. Educational background varied across coaches (12% high school degree, 51% bachelor's degree, 32% master's degree, 2% doctoral degree, 1.5% JD degree). Few coaches (20%) were or had been licensed health care providers or carried malpractice insurance (38%). Coaches usually provided services for children < 4 months of age to about 6 years of age, and were much less likely to provide services for children with comorbid neurodevelopmental (32%) or significant medical disorders (19%). Coaches reported an average of 3 new and 6 total clients per week and working 20 hr per week on average. Most coaches (76%) felt that a formal sleep coach training program was the most important qualification for practice. CONCLUSIONS: These results highlight a diversity of background, training, and geographical distribution of sleep coaches, and may help inform discussions regarding guidelines for training and credentialing of sleep coaches. PMID- 27362894 TI - Higher Molecular Mass Organic Matter Molecules Compete with Orthophosphate for Adsorption to Iron (Oxy)hydroxide. AB - The competition between orthophosphate and water-extractable organic matter (WEOM) for adsorption to iron (oxy)hydroxide mineral surfaces is an important factor in determining the plant bioavailability of P in soils. Chemical force spectroscopy was used to determine the binding force between orthophosphate and iron (oxy)hydroxide that was coated onto atomic force microscopy (AFM) tips and adsorbed with WEOM. The force measurements were conducted at pH 4.65 and 0.02 M ionic strength which are representative of typical acid soil solutions. The chemical composition of the WEOM was determined by ultrahigh resolution electrospray ionization Fourier transform ion cyclotron mass spectrometry. The results indicate a correlation between aromatic WEOM molecules that are greater than 600 Da and the reduced binding force of orthophosphate to WEOM-adsorbed iron (oxy)hydroxide AFM tips suggesting that the molecular mass of aromatic WEOM molecules plays a critical role in regulating the WEOM-P interactions with surface functional groups of minerals. Based on the results of this study, we show the importance of obtaining a detailed, molecular-scale understanding of soil processes that can help develop better management strategies to reduce waste of limited P resources and adverse environmental impacts. Specifically, soil amendments with greater content of high molecular mass aromatic components may positively affect dissolved P use efficiency in soils by maintaining P in soil solution. PMID- 27362895 TI - Depletion-Mode GaN HEMT Q-Spoil Switches for MRI Coils. AB - Q-spoiling is the process of decoupling an MRI receive coil to protect the equipment and patient. Conventionally, Q-spoiling is performed using a PIN diode switch that draws significant current. In this work, a Q-spoiling technique using a depletion-mode Gallium Nitride HEMT device was developed for coil detuning at both 1.5 T and 3 T MRI. The circuits with conventional PIN diode Q-spoiling and the GaN HEMT device were implemented on surface coils. SNR was measured and compared for all surfaces coils. At both 1.5 T and 3 T, comparable SNR was achieved for all coils with the proposed technique and conventional Q-spoiling. The GaN HEMT device has significantly reduced the required power for Q-spoiling. The GaN HEMT device also provides useful safety features by detuning the coil when unpowered. PMID- 27362896 TI - Seasonal Dynamics and Spatial Distribution of the Dactylogyrus Species on the Gills of Grass Carp (Ctenopharyngodon idellus) from a Fish Pond in Wuhan, China. AB - Spatial distribution and seasonal variation in mean intensity and prevalence of monogeneans on the gills of grass carp ( Ctenopharyngodon idellus ) were investigated from September 2012 to December 2014 in a fish pond in Wuhan, China. During this period, 2 species of Dactylogyrus were found, i.e., Dactylogyrus lamellatus and Dactylogyrus ctenopharyngodonis. Dactylogyrus lamellatus was present during the entire duration of the investigation, whereas D. ctenopharyngodonis was only detected after January 2014, when another batch of grass carp fingerlings was added to the pond. Prevalence of the 2 Dactylogyrus spp. was relatively high throughout the year, but significant seasonal changes were detected in the mean intensity of the 2 species (P < 0.05). Mean intensity of D. lamellatus peaked in late winter and spring, and then dropped to the lowest point in summer. Dactylogyrus ctenopharyngodonis exhibited a high mean intensity in summer and autumn, but low in winter and spring. Spatial distribution of the 2 species was similar: the highest mean intensity was found on medial and distal parts of the second gill arch. Moreover, no evident change was detected in niche preference of D. lamellatus after the infection of D. ctenopharyngodonis occurred. There was no significant positive correlation in abundance between the 2 species (P > 0.05). In addition, there were no significant differences in the percentage of mean intensity of the 2 species on each gill arch among low-, medium-, and high-intensity groups (P > 0.05). These results suggest unsaturated gill niches and the absence of interspecific competition between the 2 Dactylogyrus species. PMID- 27362897 TI - The influence of gender on respiratory outcomes in children with bronchopulmonary dysplasia during the first 3 years of life. AB - INTRODUCTION: Since premature males are more likely to be diagnosed with bronchopulmonary dysplasia we hypothesized that differences in respiratory outcomes after initial hospital discharge and during the first 3 years of life would exist between females and males diagnosed with BPD. METHODS: Subjects with the diagnosis of BPD were recruited from the Johns Hopkins Bronchopulmonary Dysplasia Clinic between 2008 and 2014. Clinical features were assessed through chart review (n = 482). Respiratory morbidities were assessed by caregiver questionnaires at clinic visits (n = 429), including emergency department visits, hospital admissions, systemic steroid use, and antibiotic use for respiratory reasons since the last BPD clinic visit or after initial hospital discharge if assessed at the first visit. RESULTS: Male infants weighed significantly more at birth, had higher birth weight percentiles and were more likely to be non-white compared to female infants. The frequency of ever acute care use was 36.9% for emergency department visits, 27.4% for hospital admissions, 36.9% for systemic steroid use, and 40.5% for antibiotic use for a respiratory illness. No differences in respiratory morbidities were found between males and females. Females however, tended to be weaned from supplemental oxygen over 3 months later than males. CONCLUSIONS: Compared to females with BPD, males were more likely to weigh more, have higher birth weight percentiles and be non-white. After initial hospital discharge, there were no difference in respiratory morbidities between males and females with BPD. Female infants however were more likely to be weaned from supplemental oxygen at a later age than male infants. Pediatr Pulmonol. 2017;52:217-224. (c) 2016 Wiley Periodicals, Inc. PMID- 27362898 TI - Intravesical Hemostatic Clip Migration After Robotic Prostatectomy: Case Series and Review of the Literature. AB - INTRODUCTION: The Weck Hem-o-lokTM Ligating clip is a routinely used hemostatic tool in robotic and laparoscopic surgery. It has been the practice in our institution to use such clips for hemostasis of the vascular bundles during robotic prostatectomy. Migration of such clips has been reported in the literature as single case reports. In this study, we present a case series of intravesical Weck clip extrusions presenting as bladder calculi. Such events have led to a change in our practice, and more research is needed to assess the impact of this change. MATERIALS AND METHODS: A retrospective chart review was conducted over the period 2006-2011. Patients included in the study required cystoscopic intervention for removal of encrusted or impacted Weck clips. Primary data points included type of intervention required, time to presentation, and number of presentations. Postoperative anastomotic leak, duration of postoperative hospital stay, and initial operative time were also investigated. RESULTS: Out of 570 total men undergoing robotic-assisted laparoscopic radical prostatectomy (RALRP), eight required return to the operating room for clip extraction (1.4%). Extraction methods included laser lithotripsy, blunt litholapaxy, and grasper extraction. Men experiencing clip migration were hospitalized for a longer period of time (7.6 days vs. 2.1 days, P < .01) and they required more blood transfusions (1.4 units vs. 0.05 units, P < .01) than men who did not experience clip migration. The most common site for clip intrusion was the bladder neck. Average time to presentation was 1.75 years. DISCUSSION: Weck clip migration is a recognized complication of robotic-assisted radical prostatectomy. Men with recurrent urinary tract infection, bothersome voiding symptoms, or hematuria following RALRP should be considered for cystoscopic evaluation. Increased length of hospital stays and the need for a larger volume blood transfusion following prostatectomy were significant predictors of clip migration. More research is needed to determine if implemented changes to our surgical technique have mitigated these risks. PMID- 27362899 TI - Targeting CDCP1 dimerization in triple-negative breast cancer. PMID- 27362901 TI - A Case of Stage 4B Seromucinous Ovarian Borderline Tumor With Endometriosis and Review of the Literature. AB - Ovarian mucinous borderline tumors are traditionally divided into 2 morphologic groups: endocervical type, also known as seromucinous, and intestinal type. We present a case of stage 4B seromucinous ovarian borderline tumor with endometriosis and review the literature. At the time of writing, this is believed to be the first case of a seromucinous borderline tumor reported at such an advanced stage. PMID- 27362900 TI - The Prognostic Value of BRCA1 and PARP Expression in Epithelial Ovarian Carcinoma: Immunohistochemical Detection. AB - BRCA1/2 mutation status in epithelial ovarian cancer (EOC) presently relies on genetic testing which is resource consuming. Immunohistochemistry is cheap, fairly reproducible, and may identify gene product alterations due to both germline and somatic mutations and other defects along the BRCA gene pathway (BRCAness phenomenon), which is important when treatment with poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors is considered. The aim of this study was to investigate immunohistochemical detection of BRCA1 and PARP expression in EOC and their possible prognostic relevance. Tumor tissue from 170 patients with EOC was stained immunohistochemically with BRCA1 and PARP antibodies. Semiquantitative analyses were performed to determine loss of, equivocal, and retained BRCA1 and high versus low PARP protein expression. These parameters were analyzed for relation with patient and clinicopathologic characteristics and overall survival. BRCA1 expression was reduced in 21.2 % of the tumors and 36.5% showed high PARP expression. No correlation between the 2 parameters or between PARP and clinicopathologic features was found. Overall survival was significantly increased in the BRCA1-reduced and equivocal groups [median survival 2.4 y (95% CI, 1.6-6.6) and 4.9 y (95 % CI, 2.3-6.7) vs. 1.5 y (95% CI, 1.3-1.9); P=0.0002]. Multivariate analysis confirmed these findings; hazard ratio=0.53 (95% CI, 0.34-0.81; P=0.0037; loss of BRCA1 expression). In conclusion, immunohistochemical BRCA1 expression in EOC holds considerable prognostic information, whereas PARP expression did not influence the outcome. The results call for validation in prospective trials. PMID- 27362902 TI - The Chemotherapy Response Score (CRS): Interobserver Reproducibility in a Simple and Prognostically Relevant System for Reporting the Histologic Response to Neoadjuvant Chemotherapy in Tuboovarian High-grade Serous Carcinoma. AB - A 3-tier histopathologic scoring system, the chemotherapy response score (CRS), was previously devised for reporting the histologic response to neoadjuvant chemotherapy in interval debulking surgery specimens of stage IIIc/IV tuboovarian high-grade serous carcinoma. This has been shown to predict the outcome and offer additional information to other methods of assessing the treatment response. In the present study, the reproducibility of this scoring system was assessed by determining the interobserver agreement among reporting pathologists. A total of 5 groups each comprising 3 pathologists with different levels of expertise were selected. The participants underwent an online tutorial on how to apply the CRS system. 40 cases (38 cases in 2 appraiser groups) were scored individually by each of the 15 pathologists. The interobserver reproducibility was calculated using Fleiss' kappa, Kendall's coefficient of concordance, and the absolute agreement between (a) individual pathologists within 1 group, (b) with the majority score agreement between all groups, and (c) with all individual scores. The CRS system was found to be highly reproducible among all the pathologists' groups (kappa=0.761). The agreement in identifying the group of patients with the best response to chemotherapy was exceptionally high (kappa=0.926). We conclude that CRS has a high interobserver reproducibility, especially in identifying the subgroup of patients with the best chemotherapy response, justifying its inclusion in clinical trials and reporting practice. PMID- 27362903 TI - PD-L1 Expression in Human Placentas and Gestational Trophoblastic Diseases. AB - One of the major immune checkpoints responsible for immune evasion in cancer cells is the interaction between programmed cell death-1 (PD-1) and its ligand (PD-L1). As human trophoblastic cells display many of the features of malignant cells such as the ability to invade normal tissue including blood vessels and are apparently not eradicated by the host immune system, we undertook the present study to determine whether PD-L1 was upregulated in different types of trophoblastic cells during normal pregnancy and in gestational trophoblastic diseases. Immunohistochemistry using an anti-PD-L1-specific antibody demonstrated that in early and term normal placentas, PD-L1 was highly expressed in syncytiotrophoblast and to a much lower extent in intermediate trophoblastic cells located in the chorion laeve and implantation site. PD-L1 immunoreactivity was undetectable in cytotrophoblastic cells. This staining pattern in normal placenta was recapitulated in various types of gestational trophoblastic disease. PD-L1 was highly expressed by syncytiotrophoblast in complete moles and choriocarcinomas. The intermediate trophoblastic neoplasms, placental site trophoblastic tumors, and epithelioid trophoblastic tumors showed variable PD-L1 immunoreactivity but at a lower intensity than in the neoplastic syncytiotrophoblast in choriocarcinoma. In addition, we observed PD-1-positive lymphocytes located within the implantation site and in trophoblastic tumors. In summary, this study describes a novel mechanism for trophoblastic cells to create a tolerogenic feto-maternal interface by upregulating PD-L1 in syncytiotrophoblast and in intermediate trophoblast. Trophoblastic tumors may also use PD-L1 expression to evade the host immune response thereby promoting their survival. PMID- 27362904 TI - Minimal-deviation Endometrioid Adenocarcinoma of the Cervix: A Case Report With Ultrastructural Analysis Demonstrating Abnormal Ciliation of the Tumor Cells. AB - Minimal-deviation endometrioid adenocarcinoma (MDEA) of the uterine cervix is a rare tumor that may be confused histologically with a number of benign lesions as well as other types of endocervical neoplasia. The histologic and immunohistochemical features of MDEA have been described in case reports and in small series, but correlation of these findings with ultrastructural examination has not been documented. Herein we report a 51-yr-old patient who underwent hysterectomy for menorrhagia and was found to have a clinically unsuspected, stage IB cervical MDEA. The light microscopic, immunohistochemical, and electron microscopic features of the tumor are described, with the most significant ultrastructural abnormality being the presence of abnormal cilia and ciliogenesis. PMID- 27362905 TI - Comprehensive Analysis of PAX8 Expression in Epithelial Malignancies of the Uterine Cervix. AB - Immunohistochemistry for transcription factor PAX8 (paired box gene 8) has recently emerged as a powerful tool in the differential diagnosis of gynecologic malignancies, especially when encountered at a metastatic site. Previous studies have shown PAX8 expression in the majority of ovarian and endometrial carcinomas; however, data regarding PAX8 expression in cervical tumors are limited. In this study PAX8 expression was evaluated in 136 epithelial malignancies of the uterine cervix-including 103 squamous cell carcinomas (SCC), 20 adenocarcinomas of usual type, 6 endometrioid adenocarcinomas, and 7 adenosquamous carcinomas-on tissue microarray slides. PAX8 immunopositivity was defined as at least weak nuclear staining in >5% of tumor cells. The majority of SCC were PAX8 negative (92%; 95/103), whereas among the endocervical adenocarcinomas PAX8 was positive in 70% (14/20) of the usual type and in 83% (5/6) of the endometrioid-type tumors. PAX8 expression was observed in 29% (2/7) of adenosquamous carcinomas. We conclude that PAX8 immunostain is negative in most cervical SCC and is less frequently expressed in endocervical adenocarcinomas as compared with the previously reported high sensitivity for ovarian and endometrial adenocarcinomas. When evaluating possible primary sites of a metastatic lesion, a negative PAX8 immunostain does not rule out common cervical epithelial malignancies. PMID- 27362906 TI - Coexistence of Different Electron-Transfer Mechanisms in the DNA Repair Process by Photolyase. AB - DNA photolyase has been the topic of extensive studies due to its important role of repairing photodamaged DNA, and its unique feature of using light as an energy source. A crucial step in the repair by DNA photolyase is the forward electron transfer from its cofactor (FADH(-) ) to the damaged DNA, and the detailed mechanism of this process has been controversial. In the present study, we examine the forward electron transfer in DNA photolyase by carrying out high level ab initio calculations in combination with a quantum mechanical/molecular mechanical (QM/MM) approach, and by measuring fluorescence emission spectra at low temperature. On the basis of these computational and experimental results, we demonstrate that multiple decay pathways exist in DNA photolyase depending on the wavelength at excitation and the subsequent transition. This implies that the forward electron transfer in DNA photolyase occurs not only by superexchange mechanism but also by sequential electron transfer. PMID- 27362907 TI - Effects of extracellular acid stimulation on rat vascular smooth muscle cell in Gas6/Axl or PI3K/Akt signaling pathway. AB - Recent studies have indicated that extracellular acid stimulation inhibited the calcification of vascular smooth muscle cells (VSMCs). Cell apoptosis played an important role in the occurrence and development of vascular calcification. We further explored the effects of Gas6/Axl or PI3K/Akt signaling pathway on the inhibition of rat VSMCs calcification in response to extracellular acid stimulation. Our study demonstrated that a high concentration of phosphorus induced apoptosis and calcification of VSMCs, decreased expression of Axl, and reduced phosphorylation of Akt. Stimulation of extracellular acid counteracted the effects as above by increasing the expression of Axl and Akt phosphorylation and decreasing the expression of activated Caspase3, which thereby decreased cell apoptosis and calcification. Moreover, the effects can be attenuated by PI3K inhibitor. Our study proved that extracellular acid stimulation played a vital role in the inhibition of rat VSMCs calcification and apoptosis in Gas6/Axl or PI3K/Akt signaling pathway. PMID- 27362909 TI - Regulating acidity, porosity, and morphology of hierarchical SAPO-11 zeolite by aging treatment. AB - A facile method to modify pore structure, acidic character, and morphology of SAPO-11 molecular sieve was proposed. Aging treatment (e.g., microwave irradiation or lyophilization) is introduced in the preparation of dry gel. It regulates the kinetics of zeolitic nucleation and growth. X-ray diffraction, scanning electron microscopy, N2-adsorption, temperature programmed desorption, laser particle analyzer, and (29)Si MAS NMR were employed to investigate the effects of aging treatments on SAPO-11 products. The experimental results indicate that depolymerization reaction of silicon species is enhanced aged by microwave irradiation with a higher temperature (90 degrees C). Ratio of SM 3 to SM 2 substituting mode increases producing more strong Bronsted acid sites. Lyophilization technology, as another aging method, was employed to control the morphology of SAPO-11. Nano-sized hierarchical SAPO-11 molecular sieve (200nm in length) is obtained with an oriented growth. Activity of hydroisomerization catalysts is regulated by aging treatment. Cracking reaction attributes to a high conversion nearly 87wt% for M90. The hydroisomerization reaction is enhanced for M40 due to a large proportion of moderate acid sites. PMID- 27362908 TI - Dilute versus concentrated vasopressin administration during laparoscopic myomectomy: a randomised controlled trial. AB - OBJECTIVE: To determine if higher-volume, fixed-dose administration of vasopressin further reduces blood loss at the time of minimally invasive myomectomy. DESIGN: Randomised multicentre clinical trial. SETTING: Tertiary-care academic centres in the USA. POPULATION: Women undergoing conventional laparoscopic or robot-assisted laparoscopic myomectomy. METHODS: All participants received the same 10-unit (U) dose of vasopressin, but were randomly assigned to one of two groups: (i) received 200 ml of diluted vasopressin solution (20 U in 400 ml normal saline), and (ii) received 30 ml of concentrated vasopressin solution (20 U in 60 ml normal saline). MAIN OUTCOME MEASURES: The primary study outcome was estimated blood loss; the study was powered to detect a 100-ml difference. RESULTS: A total of 152 women were randomised; 76 patients in each group. Baseline demographics were similar between groups. The primary outcome of intraoperative blood loss was not significantly different, as measured by three parameters: surgeon estimate (mean estimated blood loss 178 +/- 265 ml and 198 +/ 232 ml, dilute and concentrated groups respectively, P = 0.65), suction canister calculated blood loss, or change in haematocrit levels. There were no vasopressin related adverse events. CONCLUSION: Both dilute and concentrated vasopressin solutions that use the same drug dosing demonstrate comparable safety and tolerability when administered for minimally invasive myomectomy; however, higher volume administration of vasopressin does not reduce blood loss. TWEETABLE ABSTRACT: This randomised trial failed to show benefit of high-volume dilute vasopression. PMID- 27362910 TI - Cell-free DNA testing of an extended range of chromosomal anomalies: clinical experience with 6,388 consecutive cases. AB - PURPOSE: Cell-free DNA (cfDNA) testing for fetal aneuploidies was broadly implemented for common trisomies and sex-chromosome anomalies (SCAs). However, such an approach identifies only 75 to 85% of clinically relevant aneuploidies. METHODS: We present a consecutive series of 6,388 cases, thus uncovering a broader array of aneuploidies, including the rare autosomal trisomies (RATs) and the maternally inherited deletion and duplication copy-number variations (CNVs), with complete and stratified follow-up by amniocentesis. Combined measurements of z-scores and the fetal fraction, in conjunction with fetal cfDNA enrichment, were used to stratify the likelihood of true and false results. RESULTS: We obtained an incremental diagnostic yield of 50%; RATs and CNVs were found to be significant causes of fetal pathology. Scrutinizing z-scores and the fetal fraction made it possible to distinguish the sources of false-negative results; predict the likelihood of false-positive results for major trisomies and SCAs; classify maternal mosaic SCAs and CNVs, preventing false-positive results; and robustly identify maternally inherited CNVs and detect recurrent genomic disorders as a standardized function of the fetal fraction. CONCLUSION: With the clinical pertinence of this broader detection scheme confirmed, we offer recommendations for its implementation.Genet Med 19 2, 169-175. PMID- 27362911 TI - Pompe disease in adulthood: effects of antibody formation on enzyme replacement therapy. AB - PURPOSE: To determine the effect of antibodies against recombinant human acid alpha-glucosidase (rhGAA) on treatment efficacy and safety, and to test whether the GAA genotype is involved in antibody formation. METHODS: We used enzyme linked immunosorbent assay (ELISA) to determine anti-rhGAA antibody titers at baseline and at 6, 12, and 36 months of rhGAA treatment. We measured the capacity of antibodies to neutralize rhGAA enzymatic activity or cellular uptake and the effects on infusion-associated reactions (IARs), muscle strength, and pulmonary function. RESULTS: Of 73 patients, 45 developed antibodies. Maximal titers were high (>=1:31,250) in 22% of patients, intermediate (1:1,250-1:31,250) in 40%, and none or low (0-1:1,250) in 38%. The common IVS1/delex18 GAA genotype was absent only in the high-titer group. The height of the titer positively correlated with the occurrence and number of IARs (P <= 0.001). On the group level, antibody titers did not correlate with treatment efficacy. Eight patients (11%) developed very high maximal titers (>=156,250), but only one patient showed high sustained neutralizing antibodies that probably interfered with treatment efficacy. CONCLUSIONS: In adults with Pompe disease, antibody formation does not interfere with rhGAA efficacy in the majority of patients, is associated with IARs, and may be attenuated by the IVS1/delex18 GAA genotype.Genet Med 19 1, 90-97. PMID- 27362912 TI - Electronic health record interventions at the point of care improve documentation of care processes and decrease orders for genetic tests commonly ordered by nongeneticists. AB - OBJECTIVE: To determine whether electronic health record (EHR) tools improve documentation of pre- and postanalytic care processes for genetic tests ordered by nongeneticists. METHODS: We conducted a nonrandomized, controlled, pre /postintervention study of EHR point-of-care tools (informational messages and template report) for three genetic tests. Chart review assessed documentation of genetic testing processes of care, with points assigned for each documented item. Multiple linear and logistic regressions assessed factors associated with documentation. RESULTS: Preimplementation, there were no significant site differences (P > 0.05). Postimplementation, mean documentation scores increased (5.9 (2.1) vs. 5.0 (2.2); P = 0.0001) and records with clinically meaningful documentation increased (score >5: 59 vs. 47%; P = 0.02) at the intervention versus the control site. Pre- and postimplementation, a score >5 was positively associated with abnormal test results (OR = 4.0; 95% CI: 1.8-9.2) and trainee provider (OR = 2.3; 95% CI: 1.2-4.6). Postimplementation, a score >5 was also positively associated with intervention site (OR = 2.3; 95% CI: 1.1-5.1) and specialty clinic (OR = 2.0; 95% CI: 1.1-3.6). There were also significantly fewer tests ordered after implementation (264/100,000 vs. 204/100,000; P = 0.03), with no significant change at the control site (280/100,000 vs. 257/100,000; P = 0.50). CONCLUSIONS: EHR point-of-care tools improved documentation of genetic testing processes and decreased utilization of genetic tests commonly ordered by nongeneticists.Genet Med 19 1, 112-120. PMID- 27362914 TI - Graphene-Templated Supported Lipid Bilayer Nanochannels. AB - The use of patterned substrates to impose geometrical restriction on the lateral mobility of molecules in supported lipid membranes has found widespread utility in studies of cell membranes. Here, we template-pattern supported lipid membranes with nanopatterned graphene. We utilize focused ion beam milling to pattern graphene on its growth substrate, then transfer the patterned graphene to fresh glass substrates for subsequent supported membrane formation. We observe that graphene functions as an excellent lateral diffusion barrier for supported lipid bilayers. Additionally, the observed diffusion dynamics of lipids in nanoscale graphene channels reveal extremely low boundary effects, a common problem with other materials. We suggest this is attributable to the ultimate thinness of graphene. PMID- 27362915 TI - Sex-differential heterologous (non-specific) effects of vaccines: an emerging public health issue that needs to be understood and exploited. AB - INTRODUCTION: Vaccines have heterologous effects on the immune system, leading to altered susceptibility to a range of pathogens, and possibly allergy and autoimmunity. Effects are often sex-differential. This review discusses the evidence, mechanisms and public health implications of the non-specific effects of vaccines (NSEs). Areas covered: This article firstly discusses the World Health Organization systematic review of the evidence for sex-differential heterologous effects of vaccines, and further PubMed indexed studies on NSEs on susceptibility to infectious diseases, allergy, autoimmunity and malignancy in animals and humans. Potential immunological mechanisms are evaluated, including sex-differential effects. Finally it describes how advances in systems biology might be applied to study such effects. Expert commentary: This section points out the need to understand immune mechanisms in order to exploit beneficial vaccine effects, and diminish deleterious ones. It suggests analysis of vaccine effects by sex is important, and discusses the future for personalised vaccines that take these effects into account. PMID- 27362913 TI - The genetic basis of classic nonketotic hyperglycinemia due to mutations in GLDC and AMT. AB - PURPOSE: The study's purpose was to delineate the genetic mutations that cause classic nonketotic hyperglycinemia (NKH). METHODS: Genetic results, parental phase, ethnic origin, and gender data were collected from subjects suspected to have classic NKH. Mutations were compared with those in the existing literature and to the population frequency from the Exome Aggregation Consortium (ExAC) database. RESULTS: In 578 families, genetic analyses identified 410 unique mutations, including 246 novel mutations. 80% of subjects had mutations in GLDC. Missense mutations were noted in 52% of all GLDC alleles, most private. Missense mutations were 1.5 times as likely to be pathogenic in the carboxy terminal of GLDC than in the amino-terminal part. Intragenic copy-number variations (CNVs) in GLDC were noted in 140 subjects, with biallelic CNVs present in 39 subjects. The position and frequency of the breakpoint for CNVs correlated with intron size and presence of Alu elements. Missense mutations, most often recurring, were the most common type of disease-causing mutation in AMT. Sequencing and CNV analysis identified biallelic pathogenic mutations in 98% of subjects. Based on genotype, 15% of subjects had an attenuated phenotype. The frequency of NKH is estimated at 1:76,000. CONCLUSION: The 484 unique mutations now known in classic NKH provide a valuable overview for the development of genotype-based therapies.Genet Med 19 1, 104-111. PMID- 27362916 TI - Synthesis of Ultrastable Ag Nanoplates/Polyethylenimine-Reduced Graphene Oxide and Its Application as a Versatile Electrochemical Sensor. AB - Investigations on Ag nanostructures/reduced graphene oxide composites have been frequently reported, yet the morphology control of those loaded Ag nanocrystals is still challenging. We herein develop a facile method to grow triangular Ag nanoplates (AgP) on polyethylenimine-modified reduced graphene oxide (AgP/PEI rGO). The AgP/PEI-rGO hybrids show unexpected high stability against chloride ions (Cl(-) ) and hydrogen peroxide (H2 O2 ), which is possibly due to the strong interaction between surface Ag atoms with the amine groups of PEI. In the chronoamperometry measurements for detecting H2 O2 , N2 H4 , and NaNO2 , the AgP/PEI-rGO hybrid shows very wide linear ranges (usually 10(-6) -10(-2) mol L( 1) for H2 O2 , N2 H4 , and NaNO2 ) and low detection limits (down to ~1*10(-7) mol L(-1) ), which demonstrate the promising electrochemical sensor applications of these metal/graphene hybrids with well-defined morphologies and facets. In addition, this strategy could be extended to the deposition of other noble metals on rGO with controlled morphologies. PMID- 27362917 TI - Metabolic Activation of Rhein: Insights into the Potential Toxicity Induced by Rhein-Containing Herbs. AB - Rhein is a major component of the many medicinal herbs such as rhubarb. Despite wide use, intoxication cases associated with rhein-containing herbs are often reported. The present work aimed to investigate if rhein was subject to metabolic activation leading to toxicity. Upon incubations with different species of liver microsomes, three monoglucuronides were identified, corresponding to two hydroxyl glucuronides and one acyl glucuronide via the carboxyl group, respectively. Further study revealed that rhein acyl glucuronide was chemically reactive, and showed cytotoxicity toward hepatocarcinoma cells. In addition, significant species differences in glucuronidation of rhein were observed between laboratory animals and humans. Reaction phenotyping experiments demonstrated that rhein acyl glucuronide was catalyzed predominantly by uridine 5'-diphospho glucuronosyltransferase 1A1, 1A9, and 2B7. Taken together, the present study confirmed that rhein could be metabolically activated via the formation of acyl glucuronide, especially in human. PMID- 27362919 TI - Cu-Catalyzed Direct C6-Arylation of Indoles. AB - The first example of direct and site-selective arylation of indoles at the C6 position has been reported. The key to this high regioselectivity is the appropriate choice of the N-P(O)(t)Bu2 directing group and the use of diaryliodonium triflate salts as the coupling partners in the presence of catalytic CuO. The protocol is distinguished by mild reaction system that avoids ligand and additives, exhibiting wide scope of indole and arene coupling components without compromising its efficiency and scalability, thus representing a significant advancement in the implementation of regioselective direct arylation of indoles. PMID- 27362918 TI - Cell Polarity Proteins in Breast Cancer Progression. AB - Breast cancer, one of the leading causes of cancer related death in women worldwide, is a heterogeneous disease with diverse subtypes that have different properties and prognoses. The developing mammary gland is a highly proliferative and invasive tissue, and some of the developmental programs may be aberrantly activated to promote breast cancer progression. In the breast, luminal epithelial cells exhibit apical-basal polarity, and the failure to maintain this organizational structure, due to disruption of polarity complexes, is implicated in promoting hyperplasia and tumors. Therefore, understanding the mechanisms underlying loss of polarity will contribute to our knowledge of the early stages leading to the pathogenesis of the disease. In this review, we will discuss recent findings that support the idea that loss of apical-basal cell polarity is a crucial step in the acquisition of the malignant phenotype. Oncogene induced loss of tissue organization shares a conserved cellular mechanism with developmental process, we will further describe the role of the individual polarity complexes, the Par, Crumbs, and Scribble, to couple cell division orientation and cell growth. We will examine symmetric or asymmetric cell divisions in mammary stem cell and their contribution to the development of breast cancer subtypes and cancer stem cells. Finally, we will highlight some of the recent advances in our understanding of the molecular mechanisms by which changes in epithelial polarity programs promote invasion and metastasis through single cell and collective cell modes. J. Cell. Biochem. 117: 2215-2223, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27362920 TI - Mg(2+)/Ca(2+) promotes the adhesion of marine bacteria and algae and enhances following biofilm formation in artificial seawater. AB - Adhesion of microorganisms in the marine environment is essential for initiation and following development of biofouling. A variety of factors play roles in regulating the adhesion. Here we report the influence of Ca(2+) and Mg(2+) in artificial seawater on attachment and colonization of Bacillus sp., Chlorella and Phaeodactylum tricornutum on silicon wafer. Extra addition of the typical divalent cations in culturing solution gives rise to significantly enhanced adhesion of the microorganisms. Mg(2+) and Ca(2+) affect the adhesion of Bacillus sp. presumably by regulating aggregation and formation of extracellular polymeric substances (EPS). The ions alter quantity and types of the proteins in EPS, in turn affecting subsequent adhesion. However, it is noted that Mg(2+) promotes adhesion of Chlorella likely by regulating EPS formation and polysaccharide synthesis. Ca(2+) plays an important role in protein expression to enhance the adhesion of Chlorella. For Phaeodactylum tricornutum, Ca(2+) expedites protein synthesis for enhanced adhesion. The results shed some light on effective ways of utilizing divalent cations to mediate formation of biofilms on the marine structures for desired performances. PMID- 27362921 TI - The osteopontin-controlled switching of calcium oxalate monohydrate morphologies in artificial urine provides insights into the formation of papillary kidney stones. AB - The protein osteopontin (OPN) plays an important role in preventing the formation of calcium oxalate monohydrate (COM) kidney stones. To gain insight into these mechanisms, crystallization was induced by addition of human kidney OPN to artificial urine (ionic strength comparable to urine; without citrate), and the OPN-COM interaction studied using a combination of scanning electron (SEM) and confocal microscopy. By SEM, we found that increasing OPN concentrations formed large monoclinic penetration twins (no protein added) and, at higher concentrations (1-, 2MUg/ml OPN), super and hyper twins with crystal habits not found in previous studies. For instance, the hyper twins indicate well-facetted gearwheel-like habits with "teeth" developed in all crystallographic directions. At OPN concentrations >=2MUg/ml, a switching to small dumbbell-shaped COM habits with fine-textured surfaces occurred. Confocal microscopy of these dumbbells indicates protein incorporation in almost the entire crystal structure (in contrast to facetted COM), proposing a threshold concentration of ~2MUg/ml OPN for the facetted to the non-facetted habit transformation. Both the gearwheel like and the dumbbell-shaped habit are again found side-by-side (presumably triggered by OPN concentration gradients within the sample) in in-vitro formed conglomerates, which resemble cross-sections of papillary kidney stones. The abrupt transformation from facetted to non-facetted habits and the unique compliance of the two in-vitro formed habits with the two main morphologies found in papillary kidney stones propose that OPN is a main effector in direct stone forming processes. Moreover, stone structures which exhibit these two morphologies side-by-side might serve as a novel indicator for OPN concentrations surrounding those structures. PMID- 27362922 TI - Grandiose and Vulnerable Narcissists: Who Is at Higher Risk for Social Networking Addiction? AB - Scholars have recently taken an interest in the connection between narcissism and Internet use, especially among users who frequent social networking sites (SNSs). Conversely, the association between narcissism and problematic use of SNSs (i.e., unregulated use that leads to negative outcomes) has been scarcely investigated. This study addresses this gap by comparing the mean levels of problematic use of SNSs among grandiose narcissists, vulnerable narcissists, and non-narcissists. A sample of 535 students completed the 16-item Narcissistic Personality Inventory, the Hypersensitive Narcissism Scale, and the Generalized Problematic Internet Use Scale-2 (GPIUS2). Vulnerable narcissists reported (a) significant higher levels on all GPIUS2 subscales and total scores than non-narcissists and (b) a stronger preference for online social interactions and higher overall levels of problematic use of SNSs than grandiose narcissists. Conversely, no significant differences were found between grandiose narcissists and non-narcissists. This study suggests that vulnerable narcissism may contribute more to problematic use of SNSs than grandiose narcissism. PMID- 27362923 TI - The Halo Effect: An Unintended Benefit of Care Pathways. AB - The objective of this study was to determine if implementation of a simplified care pathway for total knee arthroplasty (TKA) would affect outcomes of total hip arthroplasty (THA) patients in the same health care system. Data were collected from a total of 5,095 consecutive THA patients in the year before and 2 years after implementation of the care pathway for TKA patients. Postimplementation increases were observed in both early activity (p < 0.0001) and continuous urinary catheter avoidance (p < 0.0001) among THA patients. These improvements in protocol adherence were associated with decreased complications (p < 0.0001), fewer 30-day readmissions (p < 0.0019), and decreased hospital length of stay (p < 0.0001). Based on these results, the implementation of a simplified care pathway for TKA patients can also improve outcomes for THA patients in the same health care system. PMID- 27362924 TI - Can Teicoplanin Be an Effective Choice for Antibiotic-Impregnated Cement Spacer in Two-Stage Revision Total Knee Arthroplasty? AB - The main purpose of this study was to evaluate the clinical results of two-stage revision total knee arthroplasty using a teicoplanin-impregnated cement spacer for infected primary total knee replacements. Twenty-five patients operated between 2005 and 2012 were included in this study. At the clinical status analysis, rate of infection eradication was assessed, physical examination was performed, Knee Society Score (KSS) was noted, isolated microorganisms were recorded, and the radiographic evaluation was performed. The mean KSS improved from 40 (range, 25-69) preoperatively to 77 (range, 32-96) at the latest follow up (p < 0.05). Methicillin-resistant Staphylococcus epidermidis was isolated in 9 of 25 patients as the most frequently isolated pathogen, and the other isolated pathogens were methicillin-susceptible S. epidermidis, methicillin-resistant Staphylococcus aureus, and methicillin-susceptible S. aureus. Infection was successfully eradicated in 24 of 25 patients. Two-stage revision of the infected primary knee replacement is a time-consuming but a reliable procedure with high rates of success. Teicoplanin was found to be an effective choice for antibiotic impregnated cement spacer applied for the eradication of the infection. PMID- 27362925 TI - Outcomes following Structural Grafting of Distal Femoral Osteochondral Injuries in Patients Aged 40 Years and Older. AB - Osteochondral lesions of the distal femur represent a challenging clinical entity, particularly in patients > 40 years of age. Microfracture has demonstrated inferior results in this population with clinical deterioration beyond 1 to 2 years postoperatively. Limited evidence exists to support alternative cartilage restoration procedures. The purpose of this study was to report functional outcomes and activity levels following cartilage restoration procedures in patients > 40 years with symptomatic distal femoral osteochondral lesions. From 2000 to 2012, 61 patients with distal femoral osteochondral injuries were retrospectively identified. Mean follow-up was 3.6 +/- 1.4 years; mean age was 51.6 years (range 40-71); 59% were male. Of 61 patients, 35 patients (57%) were treated with synthetic scaffold (SS) plugs (off-label), 14 (23%) with osteochondral allograft (OCA), and 12 (20%) with autologous osteochondral transfer (AOT). Validated outcome measures including activity of daily living (ADL) score, International Knee Documentation Committee (IKDC) subjective evaluation form, and Marx activity scale (MAS) were used. The average lesion size was 3.8 +/- 2.1 cm2. Lesion size was significantly greater in the OCA group (5.8 +/- 1.8 cm2), compared with the SS (3.2 +/- 1.9 cm2) and AOT group (3.3 +/- 1.8 cm2, p <= 0.0024). Collectively, outcome scores for the entire population demonstrated significant improvement in ADL (61.36 +/- 17.76-76.81 +/- 17.2, p < 0.0001) and IKDC scores (40.28 +/- 13.28-61.84 +/- 20.83, p < 0.001) from baseline to final follow-up, with no significant change in MAS (4.19 +/- 5.13 2.59 +/- 3.92, p = 0.07). Similarly, subgroup analysis identified that all treatment groups (SS, OCA, and AOT) demonstrated significant improvement in ADL and IKDC scores from preoperative to final postoperative visit (p <= 0.0361). MAS scores were maintained in the OCA and AOT groups (p >= 0.1704), but significantly decreased in the SS group (4.3 +/- 5.2-2.7 +/- 4.11, p = 0.0163). Ten patients (16.3%) required revision surgery at a mean of 4.4 years (range 0.3-13.4 years). Cartilage restoration procedures using structural grafts are successful in patients 40 years and older, with improved pain and functional outcome scores compared with preoperative baseline scores. OCA and AOT should primarily be used, given recent concerns with SS implants. PMID- 27362926 TI - Factors Affecting Mobility after Knee Arthroplasty. AB - Restricted mobility is a major issue for individuals with knee osteoarthritis (OA). Total knee arthroplasty (TKA) is expected to improve mobility in people with knee OA by alleviating pain and improving walking ability. The present study aimed to describe the time course of mobility after TKA and to identify the factors affecting mobility after TKA. This prospective cohort study comprised 62 patients undergoing TKA, evaluated at 1 month preoperatively, as well as at 1, 3, and 6 months postoperatively. Outcome measures included mobility (Life Space Assessment; LSA), self-efficacy for walking tasks (modified Gait Efficacy Scale; mGES), and physical (quadriceps strength and the Timed Up and Go; TUG test) and knee function (the Knee Society Score questionnaire). As a result, a total of 59 patients (mean age: 71.7 years; range: 58-79 years) had completed all postoperative assessments. Compared with preoperative values, patients showed decreased LSA and mGES scores at 1 month postoperatively. We found improvements in those scores from the 1-month to the 3- and 6-month assessment; however, there was no difference in the LSA and mGES scores between the preoperative and 6-month assessment. We also found improvements in quadriceps strength, the TUG score, the Knee Society Score, and pain scores from the preoperative to the 6-month assessment. Additionally, at 6 months postoperatively, the mGES and TUG scores significantly affected mobility. Our results suggest that mobility at 6 months after TKA is similar to preoperative level and self-efficacy for walking tasks and functional ability are important factors in improving mobility after TKA. PMID- 27362927 TI - Low Albumin Is a Risk Factor for Complications after Revision Total Knee Arthroplasty. AB - Low serum albumin has been shown in the primary joint arthroplasty setting to increase the rate of perioperative complications. Our present work examined a large national inpatient administrative dataset to study the relationship between serum albumin level and key outcome measures after revision total knee arthroplasty (RTKA). Our hypothesis was that lower serum albumin would be an independent risk factor for poor outcomes after RTKA. We analyzed the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database from 2006 to 2014, specifically evaluating patients undergoing RTKA. Patients were grouped as having hypoalbuminemia (serum albumin < 3.5 mg/dL) or normal albumin (serum albumin >= 3.5). We analyzed data on 22 complications as reported in the NSQIP database and developed composite complication variables (any infections, cardiac/pulmonary complications, and any major complications). For each complication, multivariable logistic regression analysis was used to evaluate its association. The cohort included 4,551 patients undergoing RTKA. Patients in the low serum albumin group were statistically more likely to develop deep surgical site infection, organ space surgical site infection, pneumonia, urinary traction infection, and sepsis. The hypoalbuminemic group was more likely to require unplanned intubation, blood transfusion intraoperatively or postoperatively, remain on a ventilator > 48 hours, and develop acute renal failure. There was also a higher risk of mortality and coma. Across the three composite complication variables, any complication (with or without transfusion), any major complication, and any infection (systemic, wound) were more prevalent among the patients with low serum albumin. This study confirms the relationship between suboptimal nutritional status and complications following RTKA. Hypoalbuminemia may be used as a potential preoperative predictor of outcomes. Understanding the effects of malnutrition on perioperative complications informs the choice of appropriate candidates for surgical intervention, timing of surgery, resource allocation, and risk counseling preoperatively. PMID- 27362928 TI - Does Conventional Lateral Long Bone Radiography Present Sagittal Axes Accurately? A Comparison with Direct Lateral Long Bone Radiography. AB - To investigate the sagittal alignment, proper and consistent radiographic evaluation is needed. We sought to use an alternative method of obtaining the same view, a direct lateral view and compare it with the conventional method. Conventional lateral long bone radiography and direct lateral long bone radiography were undertaken by 74 consecutive patients undergoing total knee arthroplasty (TKA), preoperatively and postoperatively. Angles between sagittal axes and the mechanical axis (MA), and the visible hip joint area were measured. Postoperative angles between the MA and femoral implant were also significantly different between the two radiologic methods of conventional and direct lateral long bone radiography (92.1 +/- 2.1 degrees vs. 94.4 +/- 2.6 degrees, p = 0.034). Hip joint visibility was significantly inferior using the direct lateral method (p < 0.001). The angles on the sagittal axes on conventional radiography of the lower extremities were different from those on direct lateral long bone radiography. The direct lateral long bone radiographs show the true lateral view, and surgeons may consider using the direct lateral method when evaluating relevant alignments before and after TKAs. For obese patients, however, conventional or combined methods should be considered because of inferior visibility of the hip joint using the direct method. PMID- 27362929 TI - Femoral Nerve Block after Anterior Cruciate Ligament Reconstruction. AB - Femoral nerve block (FNB) has been proposed for pain control following anterior cruciate ligament (ACL) reconstruction. Although numerous studies have assessed the efficacy of FNBs, there has been little to no research into the effect of such blocks on postoperative strength and patient-reported outcomes. We hypothesized that performance of an FNB would result in decreased quadriceps strength and poorer patient-reported outcome scores within the first 6 months following ACL reconstruction. A total of 30 patients scheduled to undergo hamstring autograft ACL reconstruction following an acute ACL injury were randomized to a single-shot FNB group or a control group. Preoperatively, patients completed a Knee Injury and Osteoarthritis Outcome Score (KOOS) and isokinetic quadriceps strength testing at 60 degrees/second. At 6 weeks postoperative, 29 of 30 patients completed a KOOS and isometric quadriceps strength testing at 90 degrees. At 6 months postoperative, 23 of 30 patients completed a KOOS and isokinetic strength testing. Quadriceps femoris strength limb symmetry indices (QF-LSI) were calculated at all time points. Repeated measures analysis of variance (ANOVA) models were then utilized to model the effect of FNB and time on QF-LSI as well as KOOS subscales for activities of daily living, pain, and symptoms. QF-LSI and all KOOS subscales demonstrated improvement with time following ACL reconstruction. Repeated measures ANOVA demonstrated that patients who underwent FNB had a mean QF-LSI that was 13.4% lower than the control group (p = 0.005) and poorer KOOS symptoms subscale scores (10.4 point difference, p = 0.032) at 6 weeks postoperative compared with controls. At 6 months postoperative, no differences were noted in QF-LSI or any of the KOOS subscales based on block status. FNB resulted in decreased strength and poorer KOOS symptom subscale score at 6 weeks following ACL reconstruction compared with controls. These differences resolved by 6 months postoperative. The long-term effect of delayed quadriceps recovery on movement patterns and functional outcome remains unknown and requires further study. The study is a randomized controlled trial with level of evidence 1. PMID- 27362930 TI - Autograft Choice in Young Female Patients: Patella Tendon versus Hamstring. AB - With the increasing incidence of anterior cruciate ligament (ACL) reconstruction in women and younger patients, the optimal graft choice in the young female patient has become the subject of much debate. This study aimed to evaluate patient-reported outcomes, objective knee stability, complication rates, and the incidence of failure after ACL reconstruction using bone-patellar tendon-bone (BPTB) autograft compared with hamstring (HS) autograft in young female patients. Female patients who underwent primary ACL reconstruction with BPTB or HS autograft between ages 15 and 25 years were identified. Medical records were reviewed for postoperative complications and subsequent procedures on the operative knee. Patients were evaluated with functional surveys, physical examination including Lachman and pivot-shift tests, and arthrometric testing with a KT-1000 arthrometer. There were 37 patients in the BPTB group and 28 patients in the HS group. For patients who did not undergo revision, significant differences were not found in visual analog score (p = 0.94), Lysholm score (p = 0.81), Kujala score (p = 0.85), or Tegner level (p = 0.81). No difference was detected in the rate of return to a level of activity at or above the same level prior to injury (p = 0.31). Significantly more patients in the BPTB group were graded 1a Lachman and negative pivot shift compared with the HS group (p < 0.001). There was a significant difference in mean side-to-side manual maximum arthrometric testing (p < 0.001). There were significantly fewer subsequent procedures and a lower rate of graft failures in the BPTB group. We detected no difference in subjective functional outcomes following ACL reconstruction. However, a higher failure rate in the HS reconstructions and greater laxity by arthrometric testing may indicate increased objective stability with the use of BPTB autograft in the young female patient population. The level of evidence for this article is (level III, retrospective cohort). PMID- 27362931 TI - Translation and Validation of the Dutch Western Ontario Meniscal Evaluation Tool. AB - The aim of this study was to translate the Western Ontario Meniscal Evaluation Tool (WOMET) into Dutch, to evaluate the content validity, construct validity, reliability, and responsiveness, and to determine the minimal important change (MIC) of the Dutch version. The WOMET was translated into Dutch according to a standardized forward-backward translation protocol. A total of 86 patients (51 males, 35 females, median age 52 years [interquartile range, 43-60 years]) with isolated meniscal pathology were included. The WOMET was completed three times; at baseline, around 2 weeks, and after 3 months from the baseline. Knee injury and osteoarthritis outcome score, International Knee Documentation Committee subjective knee form, short-form 36, and an anchor question were also answered. There were good results for content validity (floor and ceiling effects [< 15%]), construct validity (79% of the predefined hypotheses were confirmed), internal consistency (Cronbach alpha = 0.87, 0.79, and 0.86 for each subscale score), test retest reliability (intraclass correlation coefficient = 0.78 for total WOMET score), and responsiveness (79% of the predefined hypotheses were confirmed). The smallest detectable change and MIC for the Dutch WOMET are 20.5 and 14.7, respectively. The Dutch version of the WOMET is valid and reliable for assessing health-related quality of life in patients with meniscal pathology. PMID- 27362932 TI - Effectiveness of Health Impact Assessments: A Synthesis of Data From Five Impact Evaluation Reports. AB - INTRODUCTION: Since the 1990s, the use of health impact assessments (HIAs) has grown for considering the potential health impacts of proposed policies, plans, programs, and projects in various sectors. Evaluation of HIA impacts is needed for understanding the value of HIAs, improving the methods involved in HIAs, and potentially expanding their application. Impact evaluations examine whether HIAs affect decisions and lead to other effects. METHODS: I reviewed HIA impact evaluations identified by literature review and professional networking. I abstracted and synthesized data on key findings, success factors, and challenges from 5 large evaluations conducted in the United States, Europe, Australia, and New Zealand and published from 2006 through 2015. These studies analyzed impacts of approximately 200 individual HIAs. RESULTS: Major impacts of HIAs were directly influencing some decisions, improving collaboration among stakeholders, increasing awareness of health issues among decision makers, and giving community members a stronger voice in local decisions. Factors that contributed to successful HIAs included engaging stakeholders, timeliness, policy and systems support for conducting HIAs, having people with appropriate skills on the HIA team, obtaining the support of decision makers, and providing clearly articulated, feasible recommendations. Challenges that may have reduced HIA success were poor timeliness, underestimation of time and resources needed, difficulty in accessing relevant data, use of jargon in HIA reports, difficulty in involving decision makers in the HIA process, and absence of a requirement to conduct HIAs. CONCLUSION: HIAs can be useful to promote health and mitigate adverse impacts of decisions made outside of the health sector. Stakeholder interactions and community engagement may be as important as direct impacts of HIAs. Multiple factors are required for HIA success. Further work could strengthen the role of HIAs in promoting equity, examine HIA impacts in specific sectors, and document the role of HIAs in a "health in all policies" approach. PMID- 27362933 TI - Legal Preemption and the Prevention of Chronic Conditions. AB - State and local legal innovations to address chronic conditions are an ongoing source of public health improvements. For decades, some of the most ingenious law and policy ideas to address the underlying causes of chronic conditions and their contributing factors have emerged from state or local public sector grassroots initiatives in diverse areas, including tobacco use, safe housing and transportation, and environmental hazards. These reforms, however, are susceptible to invalidation through the legal doctrine of preemption. Embedded throughout our constitutional system, preemption refers to how state or local laws may be averted, displaced, or negated by conflicting laws at a higher level of government. Preemption can be complex in concept and application, leading to considerable confusion among public health leaders seeking to generate meaningful policy proposals. The objective of this article is to unravel the legal concept of preemption, explain its use as a tool to both thwart or further public health interventions, and offer practical guidance for how to legally navigate around it to address factors underlying chronic conditions. PMID- 27362934 TI - An Environmental Scan of Recent Initiatives Incorporating Social Determinants in Public Health. PMID- 27362935 TI - Targeted immunotherapy using anti-CD138-interferon alpha fusion proteins and bortezomib results in synergistic protection against multiple myeloma. AB - Although recent advances have substantially improved the management of multiple myeloma, it remains an incurable malignancy. We now demonstrate that anti-CD138 molecules genetically fused to type I interferons (IFN) synergize with the approved therapeutic bortezomib in arresting the proliferation of human multiple myeloma cell lines both in vitro and in vivo. The anti-CD138-IFNalpha14 fusion protein was active in inducing increased expression of signal transducer and activator of transcription 1 (STAT1) and its phosphorylation while the cell death pathway induced by bortezomib included generation of reactive oxygen species. Interferon regulatory factor 4 (IRF4), an important survival factor for myeloma cells, was down regulated following combination treatment. Induction of cell death appeared to be caspase-independent because treatment with inhibitors of caspase activation did not decrease the level of cell death. The observed caspase independent synergistic cell death involved mitochondrial membrane depolarization, and poly(ADP-ribose) polymerase-1 (PARP-1) cleavage, and resulted in enhanced induction of apoptosis. Importantly, using 2 different in vivo xenograft models, we found that combination therapy of anti-CD138-IFNalpha14 and bortezomib was able to cure animals with established tumors (7 of 8 using OCI-My5 or 8 of 8 using NCI-H929). Thus, the combination of anti-CD138-IFNalpha with bortezomib shows great promise as a novel therapeutic approach for the treatment of multiple myeloma, a malignancy for which there are currently no cures. PMID- 27362936 TI - Rapid carbon loss and slow recovery following permafrost thaw in boreal peatlands. AB - Permafrost peatlands store one-third of the total carbon (C) in the atmosphere and are increasingly vulnerable to thaw as high-latitude temperatures warm. Large uncertainties remain about C dynamics following permafrost thaw in boreal peatlands. We used a chronosequence approach to measure C stocks in forested permafrost plateaus (forest) and thawed permafrost bogs, ranging in thaw age from young (<10 years) to old (>100 years) from two interior Alaska chronosequences. Permafrost originally aggraded simultaneously with peat accumulation (syngenetic permafrost) at both sites. We found that upon thaw, C loss of the forest peat C is equivalent to ~30% of the initial forest C stock and is directly proportional to the prethaw C stocks. Our model results indicate that permafrost thaw turned these peatlands into net C sources to the atmosphere for a decade following thaw, after which post-thaw bog peat accumulation returned sites to net C sinks. It can take multiple centuries to millennia for a site to recover its prethaw C stocks; the amount of time needed for them to regain their prethaw C stocks is governed by the amount of C that accumulated prior to thaw. Consequently, these findings show that older peatlands will take longer to recover prethaw C stocks, whereas younger peatlands will exceed prethaw stocks in a matter of centuries. We conclude that the loss of sporadic and discontinuous permafrost by 2100 could result in a loss of up to 24 Pg of deep C from permafrost peatlands. PMID- 27362937 TI - Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines. AB - Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA resistant one, the BT474 cell line, which depicts several alterations of the "kinome". Using high-resolution nano-LC-LTQ-Orbitrap mass spectrometry associated to phosphopeptide enrichment, we found that several proteins involved in signaling and in transcription, are differentially phosphorylated before and after RA addition. The paradigm of these proteins is the RA receptor alpha (RARalpha), which was phosphorylated in MCF7 cells but not in BT474 cells after RA addition. The panel of the RA-regulated genes was also different. Overall our results indicate that RA resistance might correlate with the deregulation of the phosphoproteome with consequences on gene expression. PMID- 27362938 TI - Control of Insulin Secretion by Production of Reactive Oxygen Species: Study Performed in Pancreatic Islets from Fed and 48-Hour Fasted Wistar Rats. AB - Mitochondria and NADPH oxidase are important sources of reactive oxygen species in particular the superoxide radical (ROS) in pancreatic islets. These molecules derived from molecular oxygen are involved in pancreatic beta-cells signaling and control of insulin secretion. We examined the involvement of ROS produced through NADPH oxidase in the leucine- and/or glucose-induced insulin secretion by pancreatic islets from fed or 48-hour fasted rats. Glucose-stimulated insulin secretion (GSIS) in isolated islets was evaluated at low (2.8 mM) or high (16.7 mM) glucose concentrations in the presence or absence of leucine (20 mM) and/or NADPH oxidase inhibitors (VAS2870-20 MUM or diphenylene iodonium-DPI-5 MUM). ROS production was determined in islets treated with dihydroethidium (DHE) or MitoSOX Red reagent for 20 min and dispersed for fluorescence measurement by flow cytometry. NADPH content variation was examined in INS-1E cells (an insulin secreting cell line) after incubation in the presence of glucose (2.8 or 16.7 mM) and leucine (20 mM). At 2.8 mM glucose, VAS2870 and DPI reduced net ROS production (by 30%) and increased GSIS (by 70%) in a negative correlation manner (r = -0.93). At 16.7 mM glucose or 20 mM leucine, both NADPH oxidase inhibitors did not alter insulin secretion neither net ROS production. Pentose phosphate pathway inhibition by treatment with DHEA (75 MUM) at low glucose led to an increase in net ROS production in pancreatic islets from fed rats (by 40%) and induced a marked increase (by 144%) in islets from 48-hour fasted rats. The NADPH/NADP+ ratio was increased when INS-1E cells were exposed to high glucose (by 4.3-fold) or leucine (by 3-fold). In conclusion, increased ROS production through NADPH oxidase prevents the occurrence of hypoglycemia in fasting conditions, however, in the presence of high glucose or high leucine levels, the increased production of NADPH and the consequent enhancement of the activity of the antioxidant defenses mitigate the excess of ROS production and allow the secretory process of insulin to take place. PMID- 27362939 TI - Finding Alternatives to the Dogma of Power Based Sample Size Calculation: Is a Fixed Sample Size Prospective Meta-Experiment a Potential Alternative? AB - Sample sizes for randomized controlled trials are typically based on power calculations. They require us to specify values for parameters such as the treatment effect, which is often difficult because we lack sufficient prior information. The objective of this paper is to provide an alternative design which circumvents the need for sample size calculation. In a simulation study, we compared a meta-experiment approach to the classical approach to assess treatment efficacy. The meta-experiment approach involves use of meta-analyzed results from 3 randomized trials of fixed sample size, 100 subjects. The classical approach involves a single randomized trial with the sample size calculated on the basis of an a priori-formulated hypothesis. For the sample size calculation in the classical approach, we used observed articles to characterize errors made on the formulated hypothesis. A prospective meta-analysis of data from trials of fixed sample size provided the same precision, power and type I error rate, on average, as the classical approach. The meta-experiment approach may provide an alternative design which does not require a sample size calculation and addresses the essential need for study replication; results may have greater external validity. PMID- 27362940 TI - Melatonin Signal Transduction Pathways Require E-Box-Mediated Transcription of Per1 and Per2 to Reset the SCN Clock at Dusk. AB - Melatonin is released from the pineal gland into the circulatory system at night in the absence of light, acting as "hormone of darkness" to the brain and body. Melatonin also can regulate circadian phasing of the suprachiasmatic nucleus (SCN). During the day-to-night transition, melatonin exposure advances intrinsic SCN neural activity rhythms via the melatonin type-2 (MT2) receptor and downstream activation of protein kinase C (PKC). The effects of melatonin on SCN phasing have not been linked to daily changes in the expression of core genes that constitute the molecular framework of the circadian clock. Using real-time RT-PCR, we found that melatonin induces an increase in the expression of two clock genes, Period 1 (Per1) and Period 2 (Per2). This effect occurs at CT 10, when melatonin advances SCN phase, but not at CT 6, when it does not. Using anti sense oligodeoxynucleotides (alpha ODNs) to Per 1 and Per 2, as well as to E-box enhancer sequences in the promoters of these genes, we show that their specific induction is necessary for the phase-altering effects of melatonin on SCN neural activity rhythms in the rat. These effects of melatonin on Per1 and Per2 were mediated by PKC. This is unlike day-active non-photic signals that reset the SCN clock by non-PCK signal transduction mechanisms and by decreasing Per1 expression. Rather, this finding extends roles for Per1 and Per2, which are critical to photic phase-resetting, to a nonphotic zeitgeber, melatonin, and suggest that the regulation of these clock gene transcripts is required for clock resetting by diverse regulatory cues. PMID- 27362941 TI - DNA Hypermethylation of CREB3L1 and Bcl-2 Associated with the Mitochondrial Mediated Apoptosis via PI3K/Akt Pathway in Human BEAS-2B Cells Exposure to Silica Nanoparticles. AB - The toxic effects of silica nanoparticles (SiNPs) are raising concerns due to its widely applications in biomedicine. However, current information about the epigenetic toxicity of SiNPs is insufficient. In this study, the epigenetic regulation of low-dose exposure to SiNPs was evaluated in human bronchial epithelial BEAS-2B cells over 30 passages. Cell viability was decreased in a dose and passage-dependent manner. The apoptotic rate, the expression of caspase-9 and caspase-3, were significantly increased induced by SiNPs. HumanMethylation450 BeadChip analysis identified that the PI3K/Akt as the primary apoptosis-related pathway among the 25 significant altered processes. The differentially methylated sites of PI3K/Akt pathway involved 32 differential genes promoters, in which the CREB3L1 and Bcl-2 were significant hypermethylated. The methyltransferase inhibitor, 5-aza, further verified that the DNA hypermethylation status of CREB3L1 and Bcl-2 were associated with downregulation of their mRNA levels. In addition, mitochondrial-mediated apoptosis was triggered by SiNPs via the downregulation of PI3K/Akt/CREB/Bcl-2 signaling pathway. Our findings suggest that long-term low-dose exposure to SiNPs could lead to epigenetic alterations. PMID- 27362943 TI - The Prerequisites for Central Tolerance Induction against Citrullinated Proteins in the Mouse. AB - OBJECTIVES: To assess the prerequisites for negative selection of peptidylcitrulline-specific T cells in the thymus. In detail, we here analyzed murine medullary thymic epithelial cells for the expression of peptidylarginine deiminases (PAD) and subsequent citrullination. METHODS: Medullary thymic epithelial cells were sorted, their mRNA was isolated and the expression of Pad genes was analyzed by quantitative PCR. Citrullination was detected by Western Blot in lysates of sorted medullary thymic epithelial cells and histologically by immunofluorescence of thymic thin sections. RESULTS: Pad2 and Pad4 are the main Pad isoforms expressed in mature medullary thymic epithelial cells of the mouse and their levels of expression are comparable to that of insulin (Ins2), another highly and promiscuously expressed protein in the thymus. Citrullination was detected in medullary thymic epithelial cells as shown by Western Blot and immunofluorescence. CONCLUSIONS: Even though we here show that the murine thymus harbors the prerequisites for central tolerance to PAD and citrullinated peptides, it remains an open question whether the emergence of peptidylcitrulline specific T cells and of autoantibodies recognizing citrullinated epitopes is caused by a failure of central or peripheral tolerance mechanisms. PMID- 27362942 TI - Epidermal Growth Factor Receptor Mutation Enhances Expression of Cadherin-5 in Lung Cancer Cells. AB - Epidermal growth factor receptor (EGFR) activation has been shown to play a critical role in tumor angiogenesis. In this study, we investigate the correlation between EGFR mutations and cadherin-5 (CDH5), which is an angiogenic factor, in lung cancer cells. Increased expression CDH5 is observed in lung cancer cells with EGFR mutations. Stable lung cancer cell lines expressing mutant (exon 19 deletion E746-A750, and exon 21 missense mutation L858R) and wild type EGFR genes are established. A significantly higher expression of CDH5 is observed in exon 19 deletion stable lung cancer cells and mouse xenografts. Further studies show that expression of CDH5 is decreased after the inhibition of EGFR and downstream Akt pathways in lung cancer cells with EGFR mutation. In addition, mutant EGFR genes potentiates angiogenesis in lung cancer cells, which is inhibited by CDH5 siRNA, and potentiates migration and invasion in lung cancer cells. Our study shows that mutant EGFR genes are associated with overexpression of CDH5 through increased phosphorylation of EGFR and downstream Akt pathways. Our result may provide an insight into the association of mutant EGFR and CDH5 expression in lung cancer and aid further development of target therapy for NSCLC in the future. PMID- 27362944 TI - Comparison of the Effectiveness of Intravitreal Ranibizumab for Diabetic Macular Edema in Vitrectomized and Nonvitrectomized Eyes. AB - PURPOSE: To compare the effectiveness of intravitreal ranibizumab (IVR) for diabetic macular edema (DME) between eyes with and without previous vitrectomy. PROCEDURES: We prospectively assessed the best-corrected visual acuity (BCVA) and central macular thickness (CMT) after IVR for 6 months. RESULTS: There were no significant differences in the baseline BCVA and CMT between both groups. In the nonvitrectomized group (n = 15), the mean changes of BCVA and CMT from baseline to month 6 were significant (p < 0.01). In the vitrectomized group (n = 10), the improvement appeared to be slower, and the mean BCVA improvement was not significant (p = 0.5), although the mean CMT decrease was significant (p < 0.05). There were no significant differences in the mean changes of BCVA and CMT between both groups at 6 months. CONCLUSIONS: The difference in the effectiveness of IVR between both groups was not significant. IVR can be a treatment option even for vitrectomized DME eyes. PMID- 27362945 TI - Portability and Structure of the Four-Helix Bundle Docking Domains of trans Acyltransferase Modular Polyketide Synthases. AB - The polypeptides of multimodular polyketide synthases self-assemble into biosynthetic factories. While the docking domains that mediate the assembly of cis-acyltransferase polyketide synthase polypeptides are well-studied, those of the more recently discovered trans-acyltransferase polyketide synthases have just started to be described. Located at the C- and N-termini of many polypeptides, these 25-residue, two-helix, pseudosymmetric motifs noncovalently connect domains both between and within modules. Domains expressed with their natural, cognate docking motifs formed complexes stable to size-exclusion chromatography with 1-10 MUM dissociation constants as measured by isothermal titration calorimetry. Deletion and swapping experiments demonstrate portability of the docking motifs. A 1.72 A-resolution structure of the N-terminal portion of the macrolactin synthase polypeptide MlnE shows an uncomplexed N-terminal docking motif to be preorganized in the conformation it assumes within the docking domain complex. PMID- 27362946 TI - Spontaneous Maturation of Neuroblastoma to Ganglioneuroma: Two Case Studies. AB - We describe two children with ganglioneuroma (GN) likely originating from incompletely resected neuroblastoma (NB) during infancy, stages 2A and 2B, who did not undergo postoperative adjuvant chemotherapies. Both NB tumors had no MYCN amplification, had TrKA but no TrkB expression, and by TUNEL had apoptosis. These findings may have contributed to spontaneous maturation of the residual primary NB and hence the favorable prognosis, which suggests surgery alone might be the sufficient initial therapy for low-risk patients. PMID- 27362947 TI - Arthropod evolution and development: recent insights from chelicerates and myriapods. AB - Research on arthropod genetics and development has added much to our understanding of animal evolution. While this work has mainly focused on insects, a growing body of research on the less studied myriapods and chelicerates is providing important new insights into arthropod genomics and development. Multiple chelicerate lineages have a high incidence of gene duplication, which is suggestive of large-scale and even whole genome duplications. Furthermore, the duplication and divergence of genes is associated with the evolution of appendage morphology and other phenotypes in chelicerates and myriapods. Recent studies of these arthropods have also helped to understand the evolution and development of segmented bodies. Further research on chelicerate and myriapod models as well as species from other orders of these subphyla has great potential to expand our understanding of the evolution of animal genomes and development. PMID- 27362948 TI - A three-coordinate iron-silylene complex stabilized by ligand-ligand dispersion forces. AB - The structural and bonding properties of a three-coordinate N-heterocyclic silyene (NHSi) complex of the iron(ii) amide [Fe{N(SiMe3)2}2] are reported. Computational studies reveal that dispersion forces between the amido SiMe3 substituents and the isopropyl substituents on the NHSi ligand significantly enhance the stability of the complex, along with Fe-to-Si pi-backbonding. PMID- 27362950 TI - Experimental Studies of the Inspection of Areas With Restricted Access Using A0 Lamb Wave Tomography. AB - Corrosion damage in inaccessible regions presents a significant challenge to the petrochemical industry, and determining the remaining wall thickness is important to establish the remaining service life. Guided wave tomography is one solution to this and involves transmitting Lamb waves through the area of interest and, subsequently, using the received signals to reconstruct a thickness map of the remaining wall thickness. This avoids the need to access all points on the surface, making the technique well suited to inspection for areas with restricted access. The influence of these areas onto the ability to detect and size surface conditions, such as corrosion damage, using guided wave tomography is assessed. For that, a guided wave tomography system is employed, which is based on low frequency A0 Lamb waves that are excited and detected with two arrays of electromagnetic acoustic transducers. Two different defect depths are considered with different contrasts relative to the nominal wall thickness, both of which are smoothly varying and well-defined. The influence of areas with restricted surface access, support locations, pipe clamps, and STOPAQ(R) coatings is experimentally tested, and their influence assessed through comparison to a baseline reconstruction without the respective restriction in place, demonstrating only a small influence on the detected value of the remaining wall thickness. PMID- 27362949 TI - Inferring Strain Mixture within Clinical Plasmodium falciparum Isolates from Genomic Sequence Data. AB - We present a rigorous statistical model that infers the structure of P. falciparum mixtures-including the number of strains present, their proportion within the samples, and the amount of unexplained mixture-using whole genome sequence (WGS) data. Applied to simulation data, artificial laboratory mixtures, and field samples, the model provides reasonable inference with as few as 10 reads or 50 SNPs and works efficiently even with much larger data sets. Source code and example data for the model are provided in an open source fashion. We discuss the possible uses of this model as a window into within-host selection for clinical and epidemiological studies. PMID- 27362951 TI - Ultrasound Shear Wave Viscoelastography: Model-Independent Quantification of the Complex Shear Modulus. AB - Ultrasound shear wave elastography methods are commonly used for estimation of mechanical properties of soft biological tissues in diagnostic medicine. A limitation of most currently used elastography methods is that they yield only the shear storage modulus ( G' ) but not the loss modulus ( G'' ). Therefore, no information on viscosity or loss tangent (tan delta) is provided. In this paper, an ultrasound shear wave viscoelastography method is developed for model independent quantification of frequency-dependent viscoelastic complex shear modulus of macroscopically homogeneous tissues. Three in vitro tissue-mimicking phantoms and two ex vivo porcine liver samples were evaluated. Shear waves were remotely induced within the samples using several acoustic radiation force pushes to generate a semicylindrical wave field similar to those generated by most clinically used elastography systems. The complex shear modulus was estimated over a broad frequency range (up to 1000 Hz) through the analytical solution of the developed inverse wave propagation problem using the measured shear wave speed and amplitude decay versus propagation distance. The shear storage and loss moduli obtained for the in vitro phantoms were compared with those from a planar shear wave method and the average differences over the whole frequency range studied were smaller than 7% and 15%, respectively. The reliability of the proposed method highlights its potential for viscoelastic tissue characterization, which may improve noninvasive diagnosis. PMID- 27362953 TI - Massively Screening the Temporal Spectra of Single Nanoparticles to Uncover the Mechanism of Nanosynthesis. AB - Nanosynthesis is the basis of nanotechnology and its applications. It is necessary to understand the growth mechanism of nanoparticles and the functions of growth factors. An effective way to study the synthesis is at the single nanoparticle level. This study reports a single nanoparticle spectrometer, which is based on a commercial dark-field microscopy and a group of narrowband filters. This spectrometer has many advantages, such as high light transparency (35%-75%), low cost (<$1500), massive screening (~200 nanoplates at a time), and a high time resolution (<5 s). By using this spectrometer, the galvanic replacement reaction (GRR) is studied on single Ag nanoplates in situ and in real time. The research reveals that GRR on single Ag nanoplates has three different types according to the change of peak wavelength during reaction. Such diverse reaction types can be attributed to the different relative reaction rates of GRR on the faces and edges of Ag nanoplate with different facets. Further research shows that the relative reaction rates of different facets vary a lot under different concentrations of tri-sodium citrate. This research successfully demonstrates that the new single nanoparticle spectrometer can study the growth of single nanoparticles and the effect of growth factors. PMID- 27362952 TI - Evaluation of the Control of West Nile Virus in Ontario: Did Risk Patterns Change from 2005 to 2012? AB - The goal of this study was to evaluate and compare the risk distribution of human cases of West Nile virus (WNV) disease in Ontario in 2005 to 2012. The objectives were to: map the risk distribution of WNV in 2005 and 2012, identify clusters of human WNV disease and determine whether the clusters are significantly different between the years 2005 and 2012. West Nile virus surveillance data were used to calculate empirical Bayesian smoothed estimates of disease incidence in southern Ontario for 2005 and 2012. Choropleth maps were generated to visualize the spatial risk distribution, and the spatial scan test was performed to identify clusters of disease. Following identification of clusters for 2005 and 2012, a Poisson model was applied to the 2012 human WNV incidence adjusted for the smoothed human WNV incidence rate from 2005 and the scan test was repeated. Two significant clusters were identified in both the year 2005 and 2012. In 2005, the primary cluster was located in the Windsor-Essex and Chatham-Kent public health units (PHUs). For 2012, the primary cluster was identified in the Golden Horseshoe area. A cluster analysis for 2012 adjusted for those identified in 2005 resulted in one significant cluster in the Windsor-Essex PHU. In 2012, the Windsor-Essex PHU remained as a high-risk area for human WNV disease when compared with the rest of southern Ontario. Although overall risk may change from year to year, public health programming should be employed to decrease the relative risk of WNV in this area. PMID- 27362954 TI - Regioselective and Stepwise Syntheses of Functionalized BODIPY Dyes through Palladium-Catalyzed Cross-Coupling Reactions and Direct C-H Arylations. AB - Regioselective and stepwise syntheses of a series of functionalized BODIPY dyes through palladium-catalyzed cross-coupling reactions and direct C-H arylations have been developed. In particular, this method allows the straightforward synthesis of 2,6-dibromo-3,5-diarylBODIPYs and 2-bromo-3-arylBODIPYs from polybrominated BODIPYs. The X-ray structure of intermediates 5a-c indicated that the palladium was first inserted into the C-Br bonds at 3,5-positions of brominated BODIPYs. The resulting 2,6-dibromo-substituted BODIPYs are potential long wavelength photosensitizers which are not easily accessible using previous methods. PMID- 27362955 TI - Therapeutic Potential of Foldamers: From Chemical Biology Tools To Drug Candidates? AB - Over the past decade, foldamers have progressively emerged as useful architectures to mimic secondary structures of proteins. Peptidic foldamers, consisting of various amino acid based backbones, have been the most studied from a therapeutic perspective, while polyaromatic foldamers have barely evolved from their nascency and remain perplexing for medicinal chemists due to their poor drug-like nature. Despite these limitations, this compound class may still offer opportunities to study challenging targets or provide chemical biology tools. The potential of foldamer drug candidates reaching the clinic is still a stretch. Nevertheless, advances in the field have demonstrated their potential for the discovery of next generation therapeutics. In this perspective, the current knowledge of foldamers is reviewed in a drug discovery context. Recent advances in the early phases of drug discovery including hit finding, target validation, and optimization and molecular modeling are discussed. In addition, challenges and focus areas are debated and gaps highlighted. PMID- 27362956 TI - Profiles of blood pressure among children and adolescents categorized by BMI and waist circumference. AB - BACKGROUND: BMI and waist circumference (WC) are two commonly used measurements for defining general and central obesity. The present study examined the profiles of blood pressure (BP) among children and adolescents categorized by BMI and WC in Shandong, China. PARTICIPANTS AND METHODS: A total of 38 810 students (19 453 boys and 19 357 girls) aged 7-17 years participated in this study. Height, weight, WC, and BP of all participants were measured, and BMI was calculated. Relatively high BP status was defined as systolic BP and/or diastolic BP >=95th percentile for age and sex. All individuals were classified into four groups (Q1 Q4) according to the age-specific and sex-specific quartiles of BMI and WC; the BP level and the prevalence of relatively high BP among the four groups were compared. RESULTS: In both boys and girls, significant differences in BP level and the prevalence of relatively high BP were observed among the four groups categorized by BMI and WC separately (P<0.01). Children and adolescents in the high BMI group (Q4) had higher systolic BP and diastolic BP than their counterparts in the low BMI group (Q1) in all age groups (P<0.01), the range of differences being 5.7-10.3, 3.6-5.6 mmHg for boys and 3.9-8.7, 2.2-5.3 mmHg for girls, respectively. Similar differences were also observed among different groups categorized by WC. CONCLUSION: High BMI and WC are associated with elevated BP. Our findings emphasize the importance of the prevention of general and central obesity to prevent future-related problems such as hypertension in children and adolescents. PMID- 27362957 TI - Preventing preterm birth. PMID- 27362958 TI - Developmental implications of children's brain networks and learning. AB - The human brain works as a synergistic system where information exchanges between functional neuronal networks. Rudimentary networks are observed in the brain during infancy. In recent years, the question of how functional networks develop and mature in children has been a hotly discussed topic. In this review, we examined the developmental characteristics of functional networks and the impacts of skill training on children's brains. We first focused on the general rules of brain network development and on the typical and atypical development of children's brain networks. After that, we highlighted the essentials of neural plasticity and the effects of learning on brain network development. We also discussed two important theoretical and practical concerns in brain network training. Finally, we concluded by presenting the significance of network training in typically and atypically developed brains. PMID- 27362959 TI - Neural substrates and potential treatments for levodopa-induced dyskinesias in Parkinson's disease. AB - Parkinson's disease (PD) is primarily a motor disorder that involves the gradual loss of motor function. Symptoms are observed initially in the extremities, such as hands and arms, while advanced stages of the disease can effect blinking, swallowing, speaking, and breathing. PD is a neurodegenerative disease, with dopaminergic neuronal loss occurring in the substantia nigra pars compacta, thus disrupting basal ganglia functions. This leads to downstream effects on other neurotransmitter systems such as glutamate, gamma-aminobutyric acid, and serotonin. To date, one of the main treatments for PD is levodopa. While it is generally very effective, prolonged treatments lead to levodopa-induced dyskinesia (LID). LID encompasses a family of symptoms ranging from uncontrolled repetitive movements to sustained muscle contractions. In many cases, the symptoms of LID can cause more grief than PD itself. The purpose of this review is to discuss the possible clinical features, cognitive correlates, neural substrates, as well as potential psychopharmacological and surgical (including nondopaminergic and deep brain stimulation) treatments of LID. PMID- 27362960 TI - Functional polymorphism of lncRNA MALAT1 contributes to pulmonary arterial hypertension susceptibility in Chinese people. AB - BACKGROUND: The long noncoding RNAs (lncRNAs) have gradually been reported to be an important class of RNAs with pivotal roles in regulation of gene expression, and thus are involved in multitudinous human complex diseases. However, the biological functions and precise mechanisms of the majority of lncRNAs are still poorly understood. METHODS: In the study, we tested genomic variations in lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) loci, and their potentially functional correlationship with pulmonary arterial hypertension (PAH) susceptibility based on a case-control study with a total of 587 PAH patients and 736 healthy controls in southern Chinese. RESULTS: We found that the rs619586A>G single nucleotide polymorphism (SNP) was significantly associated with PAH risk. The carriers with G variant genotypes had a decreased risk of PAH (odds ratio [OR]=0.69, 95% confidence interval [CI]=0.53-0.90, p=0.007) compared to the rs619586AA genotype. Further functional experiments indicated that the alteration from rs619586A to G in MALAT1 could directly upregulate X box-binding protein 1 (XBP1) expression via functioning as the competing endogenous RNA (ceRNA) for miR 214, and consequentially inhibiting the vascular endothelial cells proliferation and migration in vitro by shortening S-M phase transition. CONCLUSIONS: Taken together, our findings propose that functional polymorphism rs619586A>G in MALAT1 gene plays an important role in PAH pathogenesis and may serve as a potential indicator for PAH susceptibility. PMID- 27362961 TI - Influence of pneumatic tube system transport on routinely assessed and spectrophotometric cerebrospinal fluid parameters. AB - BACKGROUND: Pneumatic tube systems (PTS) are widely used in many hospitals. Using PTS reduces turnaround time (TAT) and can improve patients' outcome. METHODS: We investigated whether clinically significant differences could be observed in CSF samples transported by pneumatic tube in comparison with samples transported by hand. Two aliquots from one sample were sent by PTS and by hand from the department of neurology or neurosurgery and compared. RESULTS: Routine cytological and biochemical assessment was compared in 27 cases. There were no statistically significant changes (transport by hand vs. PTS) in glucose levels [data are expressed as median (minimum-maximum)] at 3.7 (2.5-8.6) mmol/L vs. 3.6 (2.7-8.6) mmol/L, p=0.96 or lactate levels at 1.8 mmol/L (1.1-5.5) vs. 1.8 mmol/L (1.1-5.4). We observed a statistically significant decline in total protein levels in samples transported by PTS at 0.56 g/L (0.19-4.29) vs. 0.49 g/L (0.18 4.3), p=0.008. We observed no changes in erythrocyte count at 5/MUL (0-40,000) vs. 5/MUL (0-40,106), mononuclear cells at 2/MUL (1-145) vs. 3/MUL (1-152), or polynuclear cells at 0/MUL (0-235) vs. 0/MUL (0-352). Spectrophotometric examination was performed in 20 cases. There were no statistically significant differences (transport by hand vs. transport by PTS) in NOA at 0.002 (0.001 1.537) vs. 0.001 (0.001-1.528), p=0.95 or NBA at 0.001 (0.001-0.231) vs. 0.001 (0.001-0.276), p=0.675. Samples transported by PTS were delivered faster than samples transported by courier (transport by hand vs. PTS) at 25 min (10-153) vs. 15 min (4-110), p=0.002. CONCLUSIONS: We found no significant changes in glucose, lactate levels and in any of the cytological parameters assessed, nor were statistically significant changes observed in the spectrophotometric parameters. We found a statistically significant decrease in total protein levels in samples transported by PTS. Transport by PTS can be faster than transport by hand. PMID- 27362962 TI - Normalisation issues in glucose measurements using phlebotomy tubes with liquid additives. PMID- 27362963 TI - Assessment of vitamin D status - a changing landscape. AB - In recent years it has been shown that vitamin D deficiency is associated with an increased incidence as well as the progression of a broad range of diseases including osteoporosis, rickets, cardiovascular disease, autoimmune disease, multiple sclerosis and cancer. Consequently, requests for the assessment of vitamin D status have increased dramatically. Despite significant progress in the analysis of vitamin D metabolites and an expansion of our pathophysiological knowledge of vitamin D, the assessment of vitamin D status remains a challenging and partially unresolved issue. Current guidelines from scientific bodies recommend the measurement of 25-hydroxy vitamin D (25-OHD) in blood as the preferred test. However, growing evidence indicates significant limitations of this test, including analytical aspects and interpretation of results. In addition, the relationships between 25-OHD and various clinical indices, such as bone mineral density and fracture risk, are rather weak and not consistent across races. Recent studies have systematically investigated new markers of vitamin D status including the vitamin D metabolite ratio (VMR) (ratio between 25-OHD and 24,25-dihydroxy vitamin D), bioavailable 25-OHD [25-OHD not bound to vitamin D binding protein (DBP)], and free 25-OHD [circulating 25-OHD bound to neither DBP nor albumin (ALB)]. These parameters may potentially change how we will assess vitamin D status in the future. Although these new biomarkers have expanded our knowledge about vitamin D metabolism, a range of unresolved issues regarding their measurement and the interpretation of results prevent their use in daily practice. It can be expected that some of these issues will be overcome in the near future so that they may be considered for routine use (at least in specialized centers). In addition, genetic studies have revealed several polymorphisms in key proteins of vitamin D metabolism that affect the circulating concentrations of vitamin D metabolites. The affected proteins include DBP, 7 dehydrocholesterol synthase and the vitamin D receptor (VDR). Here we aim to review existing knowledge regarding the biochemistry, physiology and measurement of vitamin D. We will also provide an overview of current and emerging biomarkers for the assessment of vitamin D status, with particular attention methodological aspects and their usefulness in clinical practice. PMID- 27362964 TI - Extending laboratory automation to the wards: effect of an innovative pneumatic tube system on diagnostic samples and transport time. AB - BACKGROUND: The innovative pneumatic tube system (iPTS) transports one sample at a time without the use of cartridges and allows rapid sending of samples directly into the bulk loader of a laboratory automation system (LAS). We investigated effects of the iPTS on samples and turn-around time (TAT). METHODS: During transport, a mini data logger recorded the accelerations in three dimensions and reported them in arbitrary area under the curve (AUC) units. In addition representative quantities of clinical chemistry, hematology and coagulation were measured and compared in 20 blood sample pairs transported by iPTS and courier. RESULTS: Samples transported by iPTS were brought to the laboratory (300 m) within 30 s without adverse effects on the samples. The information retrieved from the data logger showed a median AUC of 7 and 310 arbitrary units for courier and iPTS transport, respectively. This is considerably below the reported limit for noticeable hemolysis of 500 arbitrary units. CONCLUSIONS: iPTS reduces TAT by reducing the hands-on time and a fast transport. No differences in the measurement results were found for any of the investigated 36 analytes between courier and iPTS transport. Based on these findings the iPTS was cleared for clinical use in our hospital. PMID- 27362965 TI - Assessment of Respiratory Complications Associated with End Stage Renal Disease in Northern Saudi Arabia. AB - BACKGROUND: The prevalence of End Stage Renal Disease (ESRD) is increasing in different parts of the Kingdom of Saudi Arabia (KSA), particularly Hail Region. Therefore, the aim of this study was to assess the respiratory complications that associated with ESRD. METHODS: In the present study, clinical, imaging and laboratory parameters were identified for 100 ESRD patients with ESRD who were referred to the Pulmonary Medicine Department at King Khalid Hospital. RESULTS: Pulmonary Edema, Pneumonia, and Pleural effusion were identified in 22%, 14%, and 16% of the referred ESRD patients, respectively. CONCLUSION: Respiratory complications are common among ESRD patients in Hail Region. PMID- 27362966 TI - Plasminogen and stroke: more is better. PMID- 27362968 TI - Effects of dry needling (DNHS technique) on the contractile properties of spastic muscles in a patient with stroke: a case report. AB - Dry needling for hypertonia and spasticity (DNHS) is a technique used for decreasing hypertonia and spasticity and for the improvement of function in patients with damage to the central nervous system. There is limited evidence supporting the effectiveness of this technique on the basis of objective assessments. The aim of the present case report was to quantify the effects of dry needling (DNHS technique) on the contractile properties of spastic muscles in an individual with stroke. The DNHS technique was applied to a 50-year-old male 2.5 years after stroke who had a complaint of spasticity. The treated muscles were biceps brachii, triceps brachii, rectus femoris, semitendinosus, biceps femoris, medial gastrocnemius, and lateral gastrocnemius. Tensiomyography was used to assess maximal displacement (Dm) of treated muscles. We performed a preintervention and postintervention measurement and a follow-up measurement 3 weeks after intervention. After the application of the DNHS technique, a decrease in the level of local muscle stiffness was observed for all muscles after intervention and at the 3-week follow-up, quantified by an increase in Dm. The usefulness of tensiomyography for detecting changes in patients with spasticity correlated with clinical measures in this field requires further research to establish the reliability of the different parameters provided by the equipment. PMID- 27362969 TI - Importance of an education programme for patients with chronic widespread pain. AB - The structured education programme for patients with chronic widespread pain is the first stage of the interdisciplinary group-based rehabilitation programme for those patients at the University Rehabilitation Institute in Ljubljana, Slovenia. The aim of our pilot study was to investigate the impact of the education programme on the patients' attribution of pain as dangerous. Ninety-three participants with chronic widespread pain volunteered for the study. They were first screened to verify whether they were suitable for inclusion in the rehabilitation programme. They filled in the Pain Catastrophizing Scale and the Tampa Scale of Kinesiophobia as part of the screening and after the education programme. The results showed a statistically significantly reduced fear of movement and catastrophizing. Hence, the education programme appears to be achieving its goals. PMID- 27362967 TI - The neural network for tool-related cognition: An activation likelihood estimation meta-analysis of 70 neuroimaging contrasts. AB - The ability to recognize and use a variety of tools is an intriguing human cognitive function. Multiple neuroimaging studies have investigated neural activations with various types of tool-related tasks. In the present paper, we reviewed tool-related neural activations reported in 70 contrasts from 56 neuroimaging studies and performed a series of activation likelihood estimation (ALE) meta-analyses to identify tool-related cortical circuits dedicated either to general tool knowledge or to task-specific processes. The results indicate the following: (a) Common, task-general processing regions for tools are located in the left inferior parietal lobule (IPL) and ventral premotor cortex; and (b) task specific regions are located in superior parietal lobule (SPL) and dorsal premotor area for imagining/executing actions with tools and in bilateral occipito-temporal cortex for recognizing/naming tools. The roles of these regions in task-general and task-specific activities are discussed with reference to evidence from neuropsychology, experimental psychology and other neuroimaging studies. PMID- 27362970 TI - A longitudinal ICF-CY-based evaluation of functioning and disability of children born with very low birth weight. AB - This paper aims to describe the longitudinal changes in disability, defined by the International Classification of Functioning, Disability, and Health - Children and Youth version (ICF-CY) biopsychosocial model, and developmental outcomes in a cohort of 56 very low birth weight children over 14-20 months. We used a neurofunctional assessment, the Griffiths Mental Development Scales Revised: 2-8 years (Griffiths 2-8) to evaluate psychomotor development and the ICF-CY questionnaire for ages 0-3 and 3-6 to address children's disability. Extension indexes on the basis of ICF-CY categories were computed, and longitudinal change was tested. Complete follow-up was available for 55 children (mean age 36.7 months, SD 6.7). Considering the sample as a whole, neurofunctional assessment, Griffiths score and disability were basically stable. When the subsample of children with the higher baseline functioning was taken into account, some degree of worsening, in terms of an increase in the number of impairments and limitations, was found. Our results show that disability profiles, neurofunctional assessment and global development were basically stable, except for the subgroup of children who were in the intermediate/high functioning cluster at baseline. The increased disability among these children might be because of the possibility to observe a wider set of age-specific problems, such as emotional, regulation and social abilities that are not detectable at an early stage of development and that might lead to reduced participation in social activities. PMID- 27362972 TI - Age-related changes analyzing shoulder kinematics by means of inertial sensors. AB - BACKGROUND: Shoulder kinematics alteration has been previously proven in subjects suffering from shoulder damage, which is also related to shoulder degenerative changes as consequence of aging. Because of that, it would be interesting to investigate age-related kinematics. The main objective was to analyze age-related differences in shoulder kinematics by means of inertial sensors in asymptomatic subjects during shoulder abduction and flexion. METHODS: Twenty-five right arms were measured (11 from the young adult group and 14 from the older adult group). In the young group, age ranged between 20 and 34years old, while in the older group age ranged between 45 and 72years old. Angular mobility and linear acceleration from the scapula, humerus and sternum as well as mobility in the glenohumeral and scapulothoracic joints were calculated by three inertial sensors. Subjects performed shoulder abduction and flexion. FINDINGS: Significant differences in mobility were found in humerus and scapula in mobility and acceleration during both tasks. Those differences varied depending on the plane analyzed. A moderate negative correlation between age and humerus and scapula ranged from -0.624** to -0.409*. A positive correlation was found in some planes. INTERPRETATION: The results from the present study suggest that humerus elevation and scapular protraction-retraction as well as medio-lateral rotation are more likely to present kinematics age-related differences, i.e. older: age is associated with less mobility and acceleration in some planes and axes. Results provide inertial tridimensional measures from shoulder complex comparing groups of different age. Findings also concur with previous research supporting age related shoulder changes. PMID- 27362971 TI - Outcomes of dementia: Systematic review and meta-analysis of hospital administrative database studies. AB - INTRODUCTION: Aim of the study was to compare various outcomes of dementia patients with elderly patients without dementia by conducting a systematic review of previous population-based studies. METHODS: The relevant studies were retrieved from search of electronic databases. RESULTS: The pooled data from included 11 studies consisted of outcomes of 1,044,131 dementia patients compared to 9,639,027 elderly patients without dementia. Meta-analysis showed that the mortality in dementia patients was 15.3% as compared to 8.7% in non-dementia cases (RR 1.70, CI 95%, 1.27-2.28, p 0.0004). However, there was significant heterogeneity between the studies (p<0.00001). Dementia patients had significantly increased overall readmission rate (OR 1.18; 95% CI, 1.08-1.29, p<0.001). They had higher complication rates for urinary tract infections (RR 2.88; 95% CI, 2.45-3.40, p<0.0001), pressure ulcers (RR 184; 95% CI, 1.31-1.46, p<0.0001), pneumonia (RR 1.66; 95% CI, 1.36-2.02, p<0.0001), delirium (RR 3.10; 95% CI, 2.31-4.15, p<0.0001), and, dehydration and electrolyte imbalance (RR 1.87; 95% CI, 1.55-2.25, p<0.0001). Dementia patients had more acute cardiac events (HR 1.16; 95% CI, 1.06-1.28, p 0.002), while fewer revascularization procedures (HR 0.12; 95% CI, 0.08-0.20, p<0.001). Patients with dementia had lesser use of ITU (reduction by 7.5%; 95% CI, 6.9-8.1), ventilation (reduction by 5.4%; 95% CI, 5.0-5.9), and dialysis (reduction by 0.5%; 95% CI, 0.4-0.8). DISCUSSION: Compared to older adult population, patients with dementia had poorer outcome. Despite higher mortality rate and readmission rate, they underwent fewer interventions and procedures. PMID- 27362973 TI - The content of docosahexaenoic acid in the suckling and the weaning diet beneficially modulates the ability of immune cells to response to stimuli. AB - The objective of the study was to isolate the effect of feeding a diet supplemented with docosahexaenoic acid (DHA) during the suckling and/or the weaning period on immune system development and function in offspring. Dams were randomized to one of two nutritionally adequate diets: control diet (N=12, 0% DHA) or DHA diet (N=8, 0.9% DHA). Diets were fed to dams throughout lactation, and then at weaning (21d), two pups per dam were randomly assigned to continue on the same diet as the dam or consume the other experimental diet for an additional 21d. At 6 weeks, splenocyte phenotypes and ex vivo cytokine production after stimulation with concanavalin A (ConA), lipopolysaccharide (LPS) or ovalbumin were assessed. Pups who received the control diet during both periods had the lowest production of IL-2 after ConA (P<.05 for interaction). Pups fed DHA during suckling had higher IL-10 production after all mitogens, regardless of the weaning diet (P<.05). Feeding DHA at weaning, regardless of the suckling diet, resulted in a lower production of IL-1beta and TNF-alpha in LPS-stimulated splenocytes and a higher proportion of total CD27+ cells (all P<.03). Our findings suggest that providing no DHA during critical periods of immune development resulted in a less efficient Th1 response upon challenge (IL-2 production). Feeding DHA during suckling had a programming effect on the ability of splenocytes to produce the regulatory cytokine IL-10. Feeding a DHA diet during weaning led to a lower TNF-alpha and IL-1beta response to a bacterial antigen. PMID- 27362974 TI - Colonic inflammation accompanies an increase of beta-catenin signaling and Lachnospiraceae/Streptococcaceae bacteria in the hind gut of high-fat diet-fed mice. AB - Consumption of an obesigenic/high-fat diet (HFD) is associated with a high colon cancer risk and may alter the gut microbiota. To test the hypothesis that long term high-fat (HF) feeding accelerates inflammatory process and changes gut microbiome composition, C57BL/6 mice were fed HFD (45% energy) or a low-fat (LF) diet (10% energy) for 36 weeks. At the end of the study, body weights in the HF group were 35% greater than those in the LF group. These changes were associated with dramatic increases in body fat composition, inflammatory cell infiltration, inducible nitric oxide synthase protein concentration and cell proliferation marker (Ki67) in ileum and colon. Similarly, beta-catenin expression was increased in colon (but not ileum). Consistent with gut inflammation phenotype, we also found that plasma leptin, interleukin 6 and tumor necrosis factor alpha concentrations were also elevated in mice fed the HFD, indicative of chronic inflammation. Fecal DNA was extracted and the V1-V3 hypervariable region of the microbial 16S rRNA gene was amplified using primers suitable for 454 pyrosequencing. Compared to the LF group, the HF group had high proportions of bacteria from the family Lachnospiraceae/Streptococcaceae, which is known to be involved in the development of metabolic disorders, diabetes and colon cancer. Taken together, our data demonstrate, for the first time, that long-term HF consumption not only increases inflammatory status but also accompanies an increase of colonic beta-catenin signaling and Lachnospiraceae/Streptococcaceae bacteria in the hind gut of C57BL/6 mice. PMID- 27362976 TI - Rapid climate-driven loss of breeding habitat for Arctic migratory birds. AB - Millions of birds migrate to and from the Arctic each year, but rapid climate change in the High North could strongly affect where species are able to breed, disrupting migratory connections globally. We modelled the climatically suitable breeding conditions of 24 Arctic specialist shorebirds and projected them to 2070 and to the mid-Holocene climatic optimum, the world's last major warming event ~6000 years ago. We show that climatically suitable breeding conditions could shift, contract and decline over the next 70 years, with 66-83% of species losing the majority of currently suitable area. This exceeds, in rate and magnitude, the impact of the mid-Holocene climatic optimum. Suitable climatic conditions are predicted to decline acutely in the most species rich region, Beringia (western Alaska and eastern Russia), and become concentrated in the Eurasian and Canadian Arctic islands. These predicted spatial shifts of breeding grounds could affect the species composition of the world's major flyways. Encouragingly, protected area coverage of current and future climatically suitable breeding conditions generally meets target levels; however, there is a lack of protected areas within the Canadian Arctic where resource exploitation is a growing threat. Given that already there are rapid declines of many populations of Arctic migratory birds, our results emphasize the urgency of mitigating climate change and protecting Arctic biodiversity. PMID- 27362975 TI - Short-acting insulin analogues versus regular human insulin for adults with type 1 diabetes mellitus. AB - BACKGROUND: Short-acting insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. OBJECTIVES: To assess the effects of short-acting insulin analogues versus regular human insulin in adults with type 1 diabetes. SEARCH METHODS: We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). SELECTION CRITERIA: We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared short-acting insulin analogues with regular human insulins in the treatment of adults with type 1 diabetes who were not pregnant. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. MAIN RESULTS: We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results.The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was 0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the insulin analogue, insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable.We also found no clear evidence for a substantial effect of insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. AUTHORS' CONCLUSIONS: Our analysis suggests only a minor benefit of short-acting insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of short acting insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed. PMID- 27362977 TI - Blind Image Quality Assessment Based on High Order Statistics Aggregation. AB - Blind image quality assessment (BIQA) research aims to develop a perceptual model to evaluate the quality of distorted images automatically and accurately without access to the non-distorted reference images. The state-of-the-art general purpose BIQA methods can be classified into two categories according to the types of features used. The first includes handcrafted features which rely on the statistical regularities of natural images. These, however, are not suitable for images containing text and artificial graphics. The second includes learning based features which invariably require large codebook or supervised codebook updating procedures to obtain satisfactory performance. These are time-consuming and not applicable in practice. In this paper, we propose a novel general purpose BIQA method based on high order statistics aggregation (HOSA), requiring only a small codebook. HOSA consists of three steps. First, local normalized image patches are extracted as local features through a regular grid, and a codebook containing 100 codewords is constructed by K-means clustering. In addition to the mean of each cluster, the diagonal covariance and coskewness (i.e., dimension wise variance and skewness) of clusters are also calculated. Second, each local feature is softly assigned to several nearest clusters and the differences of high order statistics (mean, variance and skewness) between local features and corresponding clusters are softly aggregated to build the global quality aware image representation. Finally, support vector regression is adopted to learn the mapping between perceptual features and subjective opinion scores. The proposed method has been extensively evaluated on ten image databases with both simulated and realistic image distortions, and shows highly competitive performance to the state-of-the-art BIQA methods. PMID- 27362978 TI - Backward Registration-Based Aspect Ratio Similarity for Image Retargeting Quality Assessment. AB - During the past few years, there have been various kinds of content-aware image retargeting operators proposed for image resizing. However, the lack of effective objective retargeting quality assessment metrics limits the further development of image retargeting techniques. Different from traditional image quality assessment (IQA) metrics, the quality degradation during image retargeting is caused by artificial retargeting modifications, and the difficulty for image retargeting quality assessment (IRQA) lies in the alternation of the image resolution and content, which makes it impossible to directly evaluate the quality degradation like traditional IQA. In this paper, we interpret the image retargeting in a unified framework of resampling grid generation and forward resampling. We show that the geometric change estimation is an efficient way to clarify the relationship between the images. We formulate the geometric change estimation as a backward registration problem with Markov random field and provide an effective solution. The geometric change aims to provide the evidence about how the original image is resized into the target image. Under the guidance of the geometric change, we develop a novel aspect ratio similarity (ARS) metric to evaluate the visual quality of retargeted images by exploiting the local block changes with a visual importance pooling strategy. Experimental results on the publicly available MIT RetargetMe and CUHK data sets demonstrate that the proposed ARS can predict more accurate visual quality of retargeted images compared with the state-of-the-art IRQA metrics. PMID- 27362979 TI - Expression strategies for structural studies of eukaryotic membrane proteins. AB - Integral membrane proteins in eukaryotes are central to various cellular processes and key targets in structural biology, biotechnology and drug development. However, the number of available structures for eukaryotic membrane protein belies their physiological importance. Recently, the number of available eukaryotic membrane protein structures has been steadily increasing due to the development of novel strategies in construct design, expression and structure determination. Here, we examine the major expression systems exploited for eukaryotic membrane proteins. Additionally we strive to tabulate and describe the recent expression strategies in eukaryotic membrane protein structural biology. We find that a majority of targets have been expressed in advanced host systems and modified from their wild-type form with distinct focus on conformation and thermostabilisation. However, strategies for native protein purification should also be considered where possible, particularly in light of the recent advances in single particle cryo electron microscopy. PMID- 27362980 TI - Combining manual therapy with pain neuroscience education in the treatment of chronic low back pain: A narrative review of the literature. AB - Teaching people with chronic low back pain (CLBP) about the neurobiology and neurophysiology of their pain is referred to as pain neuroscience education (PNE). There is growing evidence that when PNE is provided to patients with chronic musculoskeletal pain, it can result in decreased pain, pain catastrophization, disability, and improved physical performance. Because the aim of PNE is to shift the patient's focus from the tissues in the low back as the source of their pain to the brain's interpretation of inputs, many clinicians could mistakenly believe that PNE should be a "hands-off," education-only approach. An argument can be made that by providing manual therapy or exercise to address local tissue pathology, the patient's focus could be brought back to the low back tissues as the source of their problem. In this narrative literature review, we present the case for a balanced approach that combines PNE with manual therapy and exercise by considering how manual therapy can also be incorporated for interventions with patients with CLBP. We propose that as well as producing local mechanical effects, providing manual therapy within a PNE context can be seen as meeting or perhaps enhancing patient expectations, and also refreshing or sharpening body schema maps within the brain. Ideally, all of this should lead to better outcomes in patients with CLBP. PMID- 27362981 TI - Extended LazyNav: Virtual 3D Ground Navigation for Large Displays and Head Mounted Displays. AB - This paper presents the extended work on LazyNav, a head-free, eyes-free and hands-free mid-air ground navigation control model presented at the IEEE 3D User Interfaces (3DUI) 2015, in particular with a new application to the head-mounted display (HMD). Our mid-air interaction metaphor makes use of only a single pair of the remaining tracked body elements to tailor the navigation. Therefore, the user can navigate in the scene while still being able to perform other interactions with her hands and head, e.g., carrying a bag, grasping a cup of coffee, or observing the content by moving her eyes and locally rotating her head. We design several body motions for navigation by considering the use of non critical body parts and develop assumptions about ground navigation techniques. Through the user studies, we investigate the motions that are easy to discover, easy to control, socially acceptable, accurate and not tiring. Finally, we evaluate the desired ground navigation features with a prototype application in both a large display (LD) and a HMD navigation scenarios. We highlight several recommendations for designing a particular mid-air ground navigation technique for a LD and a HMD. PMID- 27362982 TI - Aggregate G-Buffer Anti-Aliasing -Extended Version. AB - We present Aggregate G-Buffer Anti-Aliasing (AGAA), a new technique for efficient anti-aliased deferred rendering of complex geometry using modern graphics hardware. In geometrically complex situations where many surfaces intersect a pixel, current rendering systems shade each contributing surface at least once per pixel. As the sample density and geometric complexity increase, the shading cost becomes prohibitive for real-time rendering. Under deferred shading, so does the required framebuffer memory. Our goal is to make high per-pixel sampling rates practical for real-time applications by substantially reducing shading costs and per-pixel storage compared to traditional deferred shading. AGAA uses the rasterization pipeline to generate a compact, pre-filtered geometric representation inside each pixel. We shade this representation at a fixed rate, independent of geometric complexity. By decoupling shading rate from geometric sampling rate, the algorithm reduces the storage and bandwidth costs of a geometry buffer, and allows scaling to high visibility sampling rates for anti aliasing. AGAA with two aggregates per-pixel generates results comparable to 32 * MSAA, but requires 54 percent less memory and is up to 2.6 * faster ( -30 percent memory and 1.7 * faster for 8 * MSAA). PMID- 27362983 TI - A Method for Locomotion Mode Identification Using Muscle Synergies. AB - Active lower limb transfemoral prostheses have enabled amputees to perform different locomotion modes such as walking, stair ascent, stair descent, ramp ascent and ramp descent. To achieve seamless mode transitions, these devices either rely on neural information from the amputee's residual limbs or sensors attached to the prosthesis to identify the intended locomotion modes or both. We present an approach for classification of locomotion modes based on the framework of muscle synergies underlying electromyography signals. Neural information at the critical instances (e.g., heel contact and toe-off) was decoded for this purpose. Non-negative matrix factorization was used to extract the muscles synergies from the muscle feature matrix. The estimation of the neural command was done using non-negative least squares. The muscle synergy approach was compared with linear discriminant analysis (LDA), support vector machine (SVM), and neural network (NN) and was tested on seven able-bodied subjects. There was no significant difference ( p > 0.05 ) in transitional and steady state classification errors during stance phase. The muscle synergy approach performed significantly better ( ) than NN and LDA during swing phase while results were similar to SVM. These results suggest that the muscle synergy approach can be used to discriminate between locomotion modes involving transitions. PMID- 27362985 TI - Detecting Pairwise Interactive Effects of Continuous Random Variables for Biomarker Identification with Small Sample Size. AB - Aberrant changes to interactions among cellular components have been conjectured to be potential causes of abnormalities in cellular functions. By systematic analysis of high-throughput-omics data, researchers hope to detect potential associations among measured variables for better biomarker identification and phenotype prediction. In this paper, we focus on the methods to measure pairwise interactive effects among continuous random variables, representing molecular expressions, with respect to a given categorical outcome. Together with a comprehensive review on the existing measures, we further propose new measures that better estimate interactive effects, especially in small sample size scenarios. We first evaluate the performance of the existing and new methods for both small and large sample sizes based on simulated datasets that shows our proposed methods outperform previous methods in general. The best performing method for small sample size scenarios suggested by simulation experiments is then implemented to estimate interactive effects among genes with respect to the metastasis outcome in two breast cancer studies based on micro-array gene expression datasets. Our results further demonstrate that integrating detected interactive effects together with individual effects can help in finding more accurate biomarkers for breast cancer metastasis, which are indeed involved in important pathways related to cancer metastasis based on gene set enrichment analysis. PMID- 27362986 TI - Extending the Applicability of Graphlets to Directed Networks. AB - With recent advances in high-throughput cell biology, the amount of cellular biological data has grown drastically. Such data is often modeled as graphs (also called networks) and studying them can lead to new insights into molecule-level organization. A possible way to understand their structure is by analyzing the smaller components that constitute them, namely network motifs and graphlets. Graphlets are particularly well suited to compare networks and to assess their level of similarity due to the rich topological information that they offer but are almost always used as small undirected graphs of up to five nodes, thus limiting their applicability in directed networks. However, a large set of interesting biological networks such as metabolic, cell signaling, or transcriptional regulatory networks are intrinsically directional, and using metrics that ignore edge direction may gravely hinder information extraction. Our main purpose in this work is to extend the applicability of graphlets to directed networks by considering their edge direction, thus providing a powerful basis for the analysis of directed biological networks. We tested our approach on two network sets, one composed of synthetic graphs and another of real directed biological networks, and verified that they were more accurately grouped using directed graphlets than undirected graphlets. It is also evident that directed graphlets offer substantially more topological information than simple graph metrics such as degree distribution or reciprocity. However, enumerating graphlets in large networks is a computationally demanding task. Our implementation addresses this concern by using a state-of-the-art data structure, the g-trie, which is able to greatly reduce the necessary computation. We compared our tool to other state-of-the art methods and verified that it is the fastest general tool for graphlet counting. PMID- 27362987 TI - Pluribus-Exploring the Limits of Error Correction Using a Suffix Tree. AB - : Next generation sequencing technologies enable efficient and cost-effective genome sequencing. However, sequencing errors increase the complexity of the de novo assembly process, and reduce the quality of the assembled sequences. Many error correction techniques utilizing substring frequencies have been developed to mitigate this effect. In this paper, we present a novel and effective method called Pluribus, for correcting sequencing errors using a generalized suffix trie. Pluribus utilizes multiple manifestations of an error in the trie to accurately identify errors and suggest corrections. We show that Pluribus produces the least number of false positives across a diverse set of real sequencing datasets when compared to other methods. Furthermore, Pluribus can be used in conjunction with other contemporary error correction methods to achieve higher levels of accuracy than either tool alone. These increases in error correction accuracy are also realized in the quality of the contigs that are generated during assembly. We explore, in-depth, the behavior of Pluribus , to explain the observed improvement in accuracy and assembly performance. Pluribus is freely available at http://compbio. CASE: edu/pluribus/. PMID- 27362988 TI - Modeling and Identification of Amnioserosa Cell Mechanical Behavior by Using Mass Spring Lattices. AB - Various mechanical models of live amnioserosa cells during Drosophila melanogaster's dorsal closure are proposed. Such models account for specific biomechanical oscillating behaviors and depend on a different set of parameters. The identification of the parameters for each of the proposed models is accomplished according to a least-squares approach in such a way to best fit the cellular dynamics extracted from live images. For the purpose of comparison, the resulting models after identification are validated to allow for the selection of the most appropriate description of such a cell dynamics. The proposed methodology is general and it may be applied to other planar biological processes. PMID- 27362990 TI - An Innovative Wireless Endoscopic Capsule With Spherical Shape. AB - This paper aims to contribute to the advancement of the Wireless Capsule Endoscopy (WCE) field for ColoRectal Cancer (CRC) screening, by developing all electronic circuits to build an innovative wireless endoscopic capsule with a spherical shape, conceived to reduce the friction during its locomotion and thus improving patient's acceptability. The proposed capsule embeds an image sensor with optics and Light Emitting Diodes (LEDs), a control unit with a telemetry module, an actuation system, a battery with a smart recharging circuit able to recharge in 20 minutes, a smart power-on circuit and a localization module. Everything is devised to fit in a small spherical shape with a diameter of 26 mm and a weight of 12.70 g. The authors present a description of the sub-modules involved in the capsule development, together with the firmware and hardware integration. In order to reduce the bandwidth for matching the specifications of the target commercial telemetry, the firmware interfacing of a custom encoder was performed, which is able to compress the incoming images with a negligible loss of information and occupying a number of Look Up-Tables (LUTs) less than 1780. As a preliminary work, a versatile Field Programmable Gate Arrays (FPGA) based demo board system has been developed in order to test and optimize the functionalities and the performance of the single sub-modules and wireless vision chain system. This work allows to demonstrate the feasibility of a complex biomedical system, with severe constraints by highlighting the necessity to enhance the frame rate in the future. PMID- 27362989 TI - A Survey of Software and Hardware Approaches to Performing Read Alignment in Next Generation Sequencing. AB - Computational genomics is an emerging field that is enabling us to reveal the origins of life and the genetic basis of diseases such as cancer. Next Generation Sequencing (NGS) technologies have unleashed a wealth of genomic information by producing immense amounts of raw data. Before any functional analysis can be applied to this data, read alignment is applied to find the genomic coordinates of the produced sequences. Alignment algorithms have evolved rapidly with the advancement in sequencing technology, striving to achieve biological accuracy at the expense of increasing space and time complexities. Hardware approaches have been proposed to accelerate the computational bottlenecks created by the alignment process. Although several hardware approaches have achieved remarkable speedups, most have overlooked important biological features, which have hampered their widespread adoption by the genomics community. In this paper, we provide a brief biological introduction to genomics and NGS. We discuss the most popular next generation read alignment tools and algorithms. Furthermore, we provide a comprehensive survey of the hardware implementations used to accelerate these algorithms. PMID- 27362991 TI - Degree-Pruning Dynamic Programming Approaches to Central Time Series Minimizing Dynamic Time Warping Distance. AB - The central time series crystallizes the common patterns of the set it represents. In this paper, we propose a global constrained degree-pruning dynamic programming (g(dp)2) approach to obtain the central time series through minimizing dynamic time warping (DTW) distance between two time series. The DTW matching path theory with global constraints is proved theoretically for our degree-pruning strategy, which is helpful to reduce the time complexity and computational cost. Our approach can achieve the optimal solution between two time series. An approximate method to the central time series of multiple time series [called as m_g(dp)2] is presented based on DTW barycenter averaging and our g(dp)2 approach by considering hierarchically merging strategy. As illustrated by the experimental results, our approaches provide better within group sum of squares and robustness than other relevant algorithms. PMID- 27362992 TI - On Stabilization of Quantized Sampled-Data Neural-Network-Based Control Systems. AB - This paper investigates the problem of stabilization of sampled-data neural network-based systems with state quantization. Different with previous works, the communication limitation of state quantization is considered for the first time. More specifically, it is assumed that the sampled state measurements from sensor to the controller are quantized via a quantizer. To reduce conservativeness, a novel piecewise Lyapunov-Krasovskii functional (LKF) is constructed by introducing a line-integral type Lyapunov function and some useful terms that take full advantage of the available information about the actual sampling pattern. Based on the new LKF, much less conservative stabilization conditions are derived to obtain the maximal sampling period and the minimal guaranteed cost control performance. The desired quantized sampled-data three-layer fully connected feedforward neural-network-based controllers are designed by a linear matrix inequality approach. A search algorithm is given to find the optimal values of tuning parameters. The effectiveness and advantage of proposed method are demonstrated by the numerical simulation of an inverted pendulum. PMID- 27362993 TI - The consumption of canned food and beverages and urinary Bisphenol A concentrations in NHANES 2003-2008. AB - BACKGROUND: Exposure to Bisphenol A (BPA) is ubiquitous and includes dietary and environmental pathways. BPA is rapidly glucuronidated in the body, and both BPA and its conjugates can be readily measured in urine. OBJECTIVES: To investigate the contribution of canned food and beverages, known sources of BPA contamination, to BPA biomarkers of exposure using dietary and urinary BPA concentration information in a representative sample of the U.S. METHODS: We evaluated 7669 NHANES 2003-2008 participants 6 years and older with 24-h dietary recall information and urinary BPA concentrations available. Using linear regression models, we evaluated the associations between recent canned food and beverage consumption and urinary BPA concentrations, adjusting for potential confounders. RESULTS: We found 9% of our participants consumed one canned food in the past 24h and 2% consumed two or more canned foods. The consumption of one canned food vs. none was associated with 24% (95% CI 1.11, 1.38) higher urinary BPA concentrations. The consumption of two or more canned foods vs. none was associated with 54% (95% CI 1.27, 1.88) higher urinary BPA concentrations. The consumption of one or more of some specific types of canned foods vs. none were associated with higher urinary BPA concentrations: 41% (95% CI 1.23, 1.63) higher BPA for vegetable and fruit, 70% (95% CI 1.18, 2.44) higher for canned pasta, and 229% (95% CI 1.22, 4.30) higher for canned soup. Canned beverages were not associated with urinary BPA concentrations. CONCLUSIONS: Canned food, including some specific types such as canned vegetable and fruit, canned pasta, and canned soup were associated with higher levels of urinary BPA concentrations. PMID- 27362995 TI - Measurement of 2-nonenal and diacetyl emanating from human skin surface employing passive flux sampler-GCMS system. AB - It is commonly said elderly persons have a characteristic body odor, and, at present, two chemical compounds have been found to vary with age in male Japanese: 2-nonenal and diacetyl. To investigate dermal emission flux of the ageing odor related compounds, we have developed a non-invasive sampling device based on a concept of passive flux sampler (PFS). The sampler was placed on the skin surface to create a headspace, and the gases emanating from skin moved toward a disk-type adsorbent. The trapped gases were then extracted with dichloromethane and determined by GCMS. The PFS was practically applied to healthy volunteers covering a wide range of age. Since emission fluxes of both compounds remarkably varied with sampling position, the nape of the neck was fixed as regular sampling position where there are dense networks of both sebaceous and eccrine glands which are potential sources of both compounds. The emission flux of 2-nonenal increased with age for both male and female volunteers, whilst the flux of diacetyl showed highest in 30s and decreased over 40s. Although diacetyl has been known as a middle-aged male odor, this study showed the odor caused by diacetyl was not specific to male. PMID- 27362994 TI - Liquid chromatography-mass spectrometry for measuring deoxythioguanosine in DNA from thiopurine-treated patients. AB - Adverse reactions and non-response are common in patients treated with thiopurine drugs. Current monitoring of drug metabolite levels for guiding treatment are limited to analysis of thioguanine nucleotides (TGNs) in erythrocytes after chemical derivatisation. Erythrocytes are not the target tissue and TGN levels show poor correlations with clinical response. We have developed a sensitive assay to quantify deoxythioguanosine (dTG) without derivatisation in the DNA of nucleated blood cells. Using liquid chromatography and detection by tandem mass spectrometry, an intra- and inter-assay variability below 7.8% and 17.0% respectively were achieved. The assay had a detection limit of 0.0003125ng (1.1 femtomoles) dTG and was quantified in DNA samples relative to endogenous deoxyadenosine (dA) in a small group of 20 patients with inflammatory bowel disease, all of whom had been established on azathioprine (AZA) therapy for more than 25 weeks. These patients had dTG levels of 20-1360mol dTG/10(6)mol dA; three patients who had not started therapy had no detectable dTG. This method, comparable to previous methods in sensitivity, enables the direct detection of a cytotoxic thiopurine metabolite without derivatisation in an easily obtainable, stable sample and will facilitate a better understanding of the mechanisms of action of these inexpensive yet effective drugs. PMID- 27362996 TI - Bio-sorption based dispersive liquid-liquid microextraction for the highly efficient enrichment of trace-level bisphenol A from water samples prior to its determination by HPLC. AB - In this study, biosorption based dispersive liquid liquid microextraction (Bio DLLME) has been developed as a new method for the extraction of bisphenol A (BPA) from water samples. In this technique, the BPA is extracted into a stable cloudy phase. The colloidal phase is composed of micro-particles made from rhaminolipid biosurfactant and methanol, which dispersed in the water samples and facilitated the breakdown of analyte matrix bonds and provided high extraction yields. Rhaminolipid biosurfactants form a thin molecular interfacial film. This layer is formed between donor and recipient phase. This molecular layer, lowers the interfacial tension between immiscible phases (aqueous solution: colloidal particles) and allow dissimilar phases to mix and interact more easily. So the equilibrium state is achieved quickly and, therefore, the extraction time is very short. The attraction of the proposed method is that the extraction is fast, simple and can be done without toxic organic solvents. Also bioaggregates have several advantages such as higher environmental compatibility and biodegradability. Experimental parameters affecting the extraction efficiency were studied and optimized. Under the optimum conditions, relative recoveries of BPA were in the ranges of 98-103.3%. The calibration plot is linear in the range between 1 and 1000MUgL(-1) (R(2)=0.998), and the relative standard deviation (RSD, for n=6) is 3.24%. PMID- 27362997 TI - What are the attributes of a good health educator? AB - OBJECTIVE: The purpose of this study was to examine the attributes that students and educators believe are important to being a good health educator in a non clinical setting. METHODS: A cross-sectional survey of first-year health science students and educators involved with a Health Science course in Melbourne, Australia was performed. A convenience sampling approach was implemented, with participants were required to rate the importance of teaching attributes on a previously developed 15-item written questionnaire. Descriptive statistics were generated, with Pearson's chi-square statistics used to examine differences between groups. In total 94/147 (63.9%) of students and 15/15 (100%) of educators participated in the study. RESULTS: Of the 15 attributes, only 'scholarly activity' was not deemed to be not as an important attribute to define a good educator. Knowledge base (50% vs. 13.3%) and feedback skills (22.3% vs. 0%) were rated as important attributes by students in comparison to educators. Professionalism (20% vs. 5.3%), scholarly activity (20% vs. 3.2%) and role modelling (26.7% vs. 3.2%) were rated as the most important attributes by educators in comparison to students. CONCLUSIONS: No single attribute makes a good health educator; rather health educators are required to have a rounded approach to teaching. Students have greater focus on the educator providing a transfer of knowledge. Educators are additionally focused on professionalism attributes, which may not be valued by students. Students and educators must enter into a clearer understanding of expectations, from both parties, to obtain optimal education outcomes. PMID- 27362998 TI - Full Angle Spatial Compound of ARFI images for breast cancer detection. AB - Automated ultrasound breast imaging would overcome most of the limitations that precludes conventional hand-held echography to be an effective screening method for breast cancer diagnosis. If a three dimensional (3D) ultrasound dataset is acquired without manual intervention of the technician, repeatability and patient follow-up could be improved. Furthermore, depending on the system configuration, resolution and contrast could be enhanced with regard to conventional echography, improving lesion detectability and evaluation. Having multiple modalities is another major advantage of these automated systems, currently under development by several research groups. Because of their circular structure, some of them include through-transmission measurements that allow constructing speed of sound and attenuation maps, which adds complementary information to the conventional reflectivity B-Mode image. This work addresses the implementation of the Acoustic Radiation Force Impulse (ARFI) imaging technique in a Full Angle Spatial Compound (FASC) automated breast imaging system. It is of particular interest because of the high specificity of ARFI for breast cancer diagnosis, by representing tissue elasticity differences rather than acoustic reflectivity. First, the image formation process is analyzed and a compounding strategy is proposed for ARFI FASC. Then, experimental results with a prototype system and two gelatin phantoms are presented: Phantom A with a hard inclusion in a soft background, and phantom B with three soft inclusions in a hard background and with three steel needles. It is demonstrated that the full angle composition of ARFI images improves image quality, enhancing Contrast to Noise Ratio (CNR) from 4.9 to 20.6 and 3.6 to 13.5 in phantoms A and B respectively. Furthermore, this CNR increase improved detectability of small structures (needles) with regard to images obtained from a single location, in which image texture masked their presence. PMID- 27362999 TI - Chemotherapy dose intensity predicted by baseline nutrition assessment in gastrointestinal malignancies: A multicentre analysis. AB - BACKGROUND: Malnutrition is prevalent in cancer patients and is associated with inferior outcomes. We examined the association between malnutrition, as measured by the Subjective Global Assessment (SGA), and chemotherapy dose reduction in patients with gastrointestinal malignancies. We hypothesised that malnutrition, defined by a patient's baseline SGA, would be associated with a greater degree of chemotherapy dose-reduction, with the implication of greater chemotherapy related toxicity. DESIGN: We reviewed chemotherapy dosing and treatment related toxicity for patients enrolled in a prospective Gastrointestinal Cancer Registry over their first 8 weeks of treatment. We compared results between well-nourished and malnourished patients. RESULTS: Malnourished patients were more likely than well nourished patients to have their starting chemotherapy dose reduced from standard published dosing (67% versus 35%, p=0.0001). Despite attenuated initial dosing, malnourished patients received a smaller fraction of planned chemotherapy (mean 80+/-23% versus 90+/-15% of cycle 1, p=0.005), primarily due to toxicity-related dose reductions. After controlling for age, gender, Eastern Cooperative Oncology Group performance status (ECOG), albumin, smoking status, body habitus, and weight loss, malnutrition remained the strongest independent predictor of the magnitude of chemotherapy dose reduction (estimate -10.3%, 95% confidence interval -19.0 to -0.1.6%, p=0.020). CONCLUSIONS: Malnutrition is an independent predictor of chemotherapy dose-reduction for toxicity. This study highlights the practical significance of malnutrition in gastrointestinal malignancies and provides a baseline for future nutrition intervention studies to improve chemotherapy tolerability in malnourished patients. PMID- 27363001 TI - Long-term changes in plaque burden and vessel remodeling in saphenous vein grafts: insights from serial intravascular ultrasound. PMID- 27363000 TI - Association of coronary artery calcium with bone mineral density in postmenopausal women. AB - OBJECTIVES: Atherosclerosis and osteoporosis (OP) are common diseases in elderly individuals and may share common pathogenetic mechanisms. The aim of this study was to investigate the association between bone mineral density (BMD) and coronary artery calcium (CAC) in postmenopausal women. METHODS: In this cross sectional study, 186 postmenopausal women 50-80 years of age were included. BMD of the spine and femoral neck was measured by dual-energy X-ray absorptiometry. The coronary artery calcium score (CACS) was measured by multidetector computed tomography. RESULTS: The study included postmenopausal women aged 65.6+/-7.3 years, 109 of whom (58.6%) showed CAC. Thirty-three (17.7%) of the patients were found to have OP in the lumbar spine and 83 (44.6%) had osteopenia, whereas in the femoral neck, 26 patients (14.0%) had OP and 87 patients (46.8%) had osteopenia. The mean CACS was 57.6+/-108.3 in normal status, 89.7+/-143.5 in OP, and 156.4+/-256.9 in osteopenia at the spine (P<0.05). The mean CACS was 43.2+/ 89.9 in normal status, 126.9+/-180.3 in OP, and 198.2+/-301.2 in osteopenia at the femoral neck (P<0.05). Multivariable logistic regression analysis showed that BMD was an independent marker for an increased risk of developing CAC in postmenopausal women. The multiple regression model showed that T-scores were the independent predictors of CACS. CONCLUSION: BMD identified on images from dual energy X-ray absorptiometry were strongly related to multidetector computed tomography measures of CAC. This low-cost, minimal radiation technique used widely for OP screening is a promising marker of generalized coronary atherosclerosis. PMID- 27363002 TI - Surgical management of interventricular septal rupture. PMID- 27363003 TI - Disorders of the anterior attentional-intentional system in patients with end stage renal disease: Evidence from reaction time studies. AB - OBJECTIVE: Dialyzed patients with end-stage renal disease (ESRD) have been reported to have several neurobehavioral impairments that are often accompanied by structural and functional abnormalities of frontal-subcortical networks. Whereas the anterior attentional-intentional systems responsible for the allocation of attention and preparation for action (intention) are mediated by these frontal-subcortical networks, these functions have not been specifically investigated in this population. METHOD: Twenty-three non-demented dialyzed patients with ESRD were compared with 25 matched controls on the performance on four reaction time (RT) subtests from the ROtman-Baycrest Battery to Investigate Attention (ROBBIA). These included measures of Simple, Choice, and Prepare RTs as well as a Concentrate task. RESULTS: In the Prepare RT task with a warning signal presented 1s before the onset of imperative stimulus, the patients' performance was not different than the controls; however, dialyzed patients became significantly slower than controls in the Prepare 3s warning condition as well as on all other RT measures. Nonetheless, both groups exhibited a gradual decrease in RT with increasing interstimulus intervals, with no group difference in the number and type of errors. CONCLUSIONS: These results suggests, that while with external preparatory stimuli, the dialyzed ESRD patients may be able to acutely increase their arousal and enhance their allocation of selective attention or action-preparation, they appear not to be able to maintain this enhanced preparatory status. Whereas these results help to elucidate a potential source of disability in this patient population, future studies will need to examine if this deficit is primarily attentional, intentional or both (arousal), as well as explore possible treatments. PMID- 27363004 TI - Featural information is sufficient to produce a left cheek bias for happiness perception. AB - People perceive the left cheek as more emotionally expressive than the right. Both configural and featural information enable the evaluation of emotional expressions; whether they make equivalent contributions to the left cheek bias is undetermined. As scrambling faces disrupts configural processing whilst leaving featural information intact, we investigated whether configural information is necessary, or featural information is sufficient, to induce a left cheek bias for emotion perception. Eighty-one participants (65 F, 16 M) viewed two types of left and right cheek image pairs - normal, scrambled - and indicated which image appeared happier (half mirror-reversed to control for perceptual biases). Results indicated a left cheek bias for both normal and scrambled faces, irrespective of mirror reversal. As scrambling faces disrupts configural processing, the fact that the left cheek was perceived as more expressive even when scrambled confirms that differences between the cheeks' featural information are sufficient to induce the left cheek bias. PMID- 27363005 TI - The procrastinators want it now: Behavioral and event-related potential evidence of the procrastination of intertemporal choices. AB - Much past research has focused on the correlation between procrastination and personality traits (e.g., impulsivity). According to the temporal motivation theory, procrastinators are impulsive and sensitive to delays in time. However, there is still a lack of direct evidence of the tendency of procrastinators to prefer immediate over future rewards. To investigate this question, we recorded event-related potentials (ERPs) in the brain while participants performed an intertemporal choice task involving both time delay and reward processing. The participants were assigned to a high procrastination group and a low procrastination group according to their scores on self-report measures. We found that high procrastination participants preferred immediate rewards compared to future ones whereas low procrastination participants did not. High procrastinators also exhibited a larger and delayed P2 component, indicating delay time processing and abnormal reward processing. No significant effect associated with procrastination was found on the P300 component. Taken together, these findings suggest that high procrastinators are more impulsive and encode the information of delay time more slowly but with a higher level of motivation driven attention. The current study substantiates higher impulsivity in procrastination and verifies that a difference exists in the sensitivity to time delay between high and low procrastinators. PMID- 27363006 TI - Non-optic vision: Beyond synesthesia? AB - Patient NS is a 28year-old female who went blind in her early twenties as a result of S-cone syndrome, a degenerative retinal disorder. A few years after losing her vision, she started experiencing visual perceptions of her hands as she moved them and objects that came into contact with her hands. Over the course of a year, these cross-modal sensations evolved to become veridical visual experiences accurately representative of her hands, objects she touched, and to some degree, objects she could infer from her immediate surroundings. We argue that these experiences are distinct from mental imagery as they occurred automatically, remained consistent over time, and were proprioceptively mediated by her head position much like normal optical vision. Moreover, she could neither consciously force these visual experiences to occur without sensory inference nor prevent them from happening when haptically exploring an object. Her previous visual experiences contributed to a strong influence of top-down processing in her perceptions. Though individuals have previously been able to develop limited veridical acquired synesthesia following extensive practice over many years with the use of a special sensory device, none reported experiencing the richness of complexity or degree of top-down processing exhibited by NS. Thus, we posit that NS's case may represent a phenomenon beyond synesthesia altogether. PMID- 27363007 TI - The effect of interference on temporal order memory in individuals with Parkinson's disease. AB - Memory for the temporal order of items or events in a sequence has been shown to be impaired in older adults and individuals with Parkinson's disease (PD). The present study examined the effects of high and low interference on temporal order memory in individuals diagnosed with PD (n=20) and demographically similar healthy older adults (n=20) utilizing a computerized task used in previously published studies. During the sample phase of each trial, a series of eight circles were randomly presented one at a time in eight different spatial locations. Participants were instructed to remember the sequence in which the circles appeared in the locations. During the choice phase, participants were presented with two circles in two different locations and were asked to indicate which circle appeared earliest in the sample phase sequence. The two circles were separated by one of four possible temporal separation lags (0, 2, 4, and 6), defined as the number of circles occurring in the sample phase sequence between the two choice phase circles. Shorter temporal lags (e.g., 0 and 2 lags) were hypothesized to result in higher interference compared to longer temporal lags (e.g., 4 and 6 lags). The results demonstrated that on trials involving high interference, no differences were found between the two groups. However, healthy older adults significantly outperformed individuals with PD (p<0.05) on trials involving low interference. Although differences were found between the PD and healthy older adult groups, both groups significantly improved on low interference trials compared to high interference trials (p<0.001). The findings indicate that temporal order memory improves in healthy older adults and individuals with PD when interference is reduced. However, individuals with PD demonstrated poorer temporal order memory even with less interference. Therefore, temporal order memory is differentially affected by interference in healthy older adults and individuals with PD. Given that both groups did improve with lessened interference, behavioral interventions that minimize temporal interference potentially could improve memory function in older adults and to a lesser extent in individuals with PD. PMID- 27363008 TI - Facing competition: Neural mechanisms underlying parallel programming of antisaccades and prosaccades. AB - The antisaccade task is a prominent tool to investigate the response inhibition component of cognitive control. Recent theoretical accounts explain performance in terms of parallel programming of exogenous and endogenous saccades, linked to the horse race metaphor. Previous studies have tested the hypothesis of competing saccade signals at the behavioral level by selectively slowing the programming of endogenous or exogenous processes e.g. by manipulating the probability of antisaccades in an experimental block. To gain a better understanding of inhibitory control processes in parallel saccade programming, we analyzed task related eye movements and blood oxygenation level dependent (BOLD) responses obtained using functional magnetic resonance imaging (fMRI) at 3T from 16 healthy participants in a mixed antisaccade and prosaccade task. The frequency of antisaccade trials was manipulated across blocks of high (75%) and low (25%) antisaccade frequency. In blocks with high antisaccade frequency, antisaccade latencies were shorter and error rates lower whilst prosaccade latencies were longer and error rates were higher. At the level of BOLD, activations in the task related saccade network (left inferior parietal lobe, right inferior parietal sulcus, left precentral gyrus reaching into left middle frontal gyrus and inferior frontal junction) and deactivations in components of the default mode network (bilateral temporal cortex, ventromedial prefrontal cortex) compensated increased cognitive control demands. These findings illustrate context dependent mechanisms underlying the coordination of competing decision signals in volitional gaze control. PMID- 27363009 TI - A multidisciplinary performance improvement rotation in an internal medicine training program. PMID- 27363010 TI - Factors influencing the detection of beach plastic debris. AB - Marine plastic pollution is a global problem with considerable ecological and economic consequences. Quantifying the amount of plastic in the ocean has been facilitated by surveys of accumulated plastic on beaches, but existing monitoring programmes assume the proportion of plastic detected during beach surveys is constant across time and space. Here we use a multi-observer experiment to assess what proportion of small plastic fragments is missed routinely by observers, and what factors influence the detection probability of different types of plastic. Detection probability across the various types of plastic ranged from 60 to 100%, and varied considerably by observer, observer experience, and biological material present on the beach that could be confused with plastic. Blue fragments had the highest detection probability, while white fragments had the lowest. We recommend long-term monitoring programmes adopt survey designs accounting for imperfect detection or at least assess the proportion of fragments missed by observers. PMID- 27363011 TI - The posterior HOXD locus: Its contribution to phenotype and malignancy of Ewing sarcoma. AB - Microarray analysis revealed genes of the posterior HOXD locus normally involved in bone formation to be over-expressed in primary Ewing sarcoma (ES). The expression of posterior HOXD genes was not influenced via ES pathognomonic EWS/ETS translocations. However, knock down of the dickkopf WNT signaling pathway inhibitor 2 (DKK2) resulted in a significant suppression of HOXD10, HOXD11 and HOXD13 while over-expression of DKK2 and stimulation with factors of the WNT signaling pathway such as WNT3a, WNT5a or WNT11 increased their expression. RNA interference demonstrated that individual HOXD genes promoted chondrogenic differentiation potential, and enhanced expression of the bone-associated gene RUNX2. Furthermore, HOXD genes increased the level of the osteoblast- and osteoclast-specific genes, osteocalcin (BGLAP) and platelet-derived growth factor beta polypeptide (PDGFB), and may further regulate endochondral bone development via induction of parathyroid hormone-like hormone (PTHLH). Additionally, HOXD11 and HOXD13 promoted contact independent growth of ES, while in vitro invasiveness of ES lines was enhanced by all 3 HOXD genes investigated and seemed mediated via matrix metallopeptidase 1 (MMP1). Consequently, knock down of HOXD11 or HOXD13 significantly suppressed lung metastasis in a xeno-transplant model in immune deficient mice, providing overall evidence that posterior HOXD genes promote clonogenicity and metastatic potential of ES. PMID- 27363012 TI - Niclosamide sensitizes triple-negative breast cancer cells to ionizing radiation in association with the inhibition of Wnt/beta-catenin signaling. AB - Triple-negative breast cancer (TNBC) is one of the most difficult breast cancers to treat because there is no targeted treatment, and conventional cytotoxic chemotherapy followed by adjuvant radiation therapy is the standard of care for patients with TNBC. We herein reported that ionizing radiation (IR) induced Wnt3a, LRP6 and beta-catenin expression and consequently activated Wnt/beta catenin signaling in TNBC MDA-MB-231, MDA-MB-468 and Hs578T cells. Moreover, depletion of beta-catenin by shRNA sensitized TNBC cells to IR, whereas treatment of Wnt3a protein or overexpression of beta-catenin resulted in radioresistance of TNBC cells. Niclosamide, a potent inhibitor of Wnt/beta-catenin signaling, not only inhibited constitutive Wnt/beta-catenin signaling, but also blocked IR induced Wnt/beta-catenin signaling in TNBC cells. In addition, niclosamide sensitized TNBC cells to IR, prevented Wnt3a-induced radioresistance, and overcame beta-catenin-induced radioresistance in TNBC cells. Importantly, animals treated with the combination of niclosamide and gamma-ray local tumor irradiation had significant inhibition of MDA-MB-231 tumor growth compared with treated with local tumor irradiation alone. These findings indicate that Wnt/beta-catenin signaling pathway plays an important role in the development of radioresistance of TNBC cells, and that niclosamide had significant radiosensitizing effects by inhibiting Wnt/beta-catenin signaling in TNBC cells. Our study also provides rationale for further preclinical and clinical evaluation of niclosamide in TNBC management. PMID- 27363013 TI - Comprehensive analysis of differentially expressed profiles of lncRNAs and circRNAs with associated co-expression and ceRNA networks in bladder carcinoma. AB - Accumulating evidences indicate that long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) play important roles in tumorigenesis. However, the mechanisms remain largely unknown. To explore lncRNAs and circRNAs expression profiling and their biological functions in bladder cancer, we surveyed the lncRNA/circRNA and mRNA expression profiles of bladder cancer and para-cancer tissues using microarray for four patients. Thousands of significantly changed lncRNAs and mRNAs as well as hundreds of circRNAs were identified. Five dysregulated lncRNAs and four mRNAs were confirmed by quantitative real-time PCR in 30 pairs of samples. GO and KEGG pathway enrichment analyses were executed to determine the principal functions of the significantly deregulated genes. Further more, we constructed correlated expression networks including coding-noncoding co expression (CNC), competing endogenous RNAs (ceRNA), cis regulation, lncRNAs transcription factor (TF)-mRNA with bioinformatics methods. Co-expression analysis showed lncRNA APLP2 expression is correlated with apoptosis-related genes, including PTEN and TP53INP1. CeRNA network inferred that lncRNA H19 and circRNA MYLK could bind competitively with miRNA-29a-3p increasing target gene DNMT3B, VEGFA and ITGB1 expressions. Moreover, the nearby genes pattern displayed that overexpressing ADAM2 and C8orf4 are cis-regulated by lncRNA RP11-359E19.2, involving in progression of bladder cancer. In addition, lncRNAs-TF-mRNA diagram indicated that lncRNA BC041488 could trans-regulate CDK1 mRNA expression through SRF transcription factor. Taken together, these results suggested lncRNAs and circRNAs could implicate in the pathogenesis and development of bladder cancer. Our findings provide a novel perspective on lncRNAs and circRNAs and lay the foundation for future research of potential roles of lncRNAs and circRNAs in bladder carcinoma. PMID- 27363014 TI - Superiority of lymph node ratio-based staging system for prognostic prediction in 2575 patients with gastric cancer: validation analysis in a large single center. AB - This study aimed to evaluate the prognostic significance of node ratio (Nr), the ratio of metastatic to retrieved lymph nodes, and to investigate whether a modified staging system based on Nr can improve prognostic ability for gastric cancer patients following gastrectomy. A total of 2572 patients were randomly divided into training set and validation set, and the cutoff points for Nr were produced using X-tile. The relationships between Nr and other clinicopathologic factors were analyzed, while survival prognostic discriminatory ability and accuracy were compared among different staging systems by AIC and C-index in R program. Patients were categorized into four groups as follows: Nr0, Nr1: 0.00 0.15, Nr2: 0.15-0.40 and Nr3: > 0.40. Nr was significantly associated with clinicopathologic factors including macroscopic type, tumor differentiation, lymphovascular invasion, perineural invasion, tumor size, T stage, N stage and TNM stage. Besides, for all patients, Nr and TNrM staging system showed a smaller AIC and a larger C-index than that of N and TNM staging system, respectively. Moreover, in subgroup analysis for patients with retrieved lymph nodes < 15, Nr was demonstrated to have a smaller AIC and a larger C-index than N staging system. Furthermore, in validation analysis, Nr, categorized by our cutoff points, showed a larger C-index and a smaller AIC value than those produced in previous studies. Nr could be considered as a reliable prognostic factor, even in patients with insufficient (< 15) retrieved lymph nodes, and TNrM staging system may improve the prognostic discriminatory ability and accuracy for gastric cancer patients undergoing radical gastrectomy. PMID- 27363016 TI - Transcriptomic analysis of KSHV-infected primary oral fibroblasts: The role of interferon-induced genes in the latency of oncogenic virus. AB - The Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), the most common HIV/AIDS-associated tumor worldwide. Involvement of the oral cavity portends a poor prognosis for patients with KS, but the mechanisms for KSHV regulation of the oral tumor microenvironment are largely unknown. Infiltrating fibroblasts are found within KS lesions, and KSHV can establish latent infection within human primary fibroblasts in vitro and in vivo, but contributions for KSHV-infected fibroblasts to the KS microenvironment have not been previously characterized. In the present study, we used Illumina microarray to determine global gene expression changes in KSHV-infected primary human oral fibroblasts (PDLF and HGF). Among significantly altered candidates, we found that a series of interferon-induced genes were strongly up-regulated in these KSHV-infected oral cells. Interestingly, some of these genes in particular ISG15 and ISG20 are required for maintenance of virus latency through regulation of specific KSHV microRNAs. Our data indicate that oral fibroblasts may represent one important host cellular defense component against viral infection, as well as acting as a reservoir for herpesvirus lifelong infection in the oral cavity. PMID- 27363015 TI - Antimitotic activity of DY131 and the estrogen-related receptor beta 2 (ERRbeta2) splice variant in breast cancer. AB - Breast cancer remains a leading cause of cancer-related death in women, and triple negative breast cancer (TNBC) lacks clinically actionable therapeutic targets. Death in mitosis is a tumor suppressive mechanism that occurs in cancer cells experiencing a defective M phase. The orphan estrogen-related receptor beta (ERRbeta) is a key reprogramming factor in murine embryonic and induced pluripotent stem cells. In primates, ERRbeta is alternatively spliced to produce several receptor isoforms. In cellular models of glioblastoma, short form (ERRbetasf) and beta2 (ERRbeta2) splice variants differentially regulate cell cycle progression in response to the synthetic agonist DY131, with ERRbeta2 driving arrest in G2/M.The goals of the present study are to determine the cellular function(s) of ligand-activated ERRbeta splice variants in breast cancer and evaluate the potential of DY131 to serve as an antimitotic agent, particularly in TNBC. DY131 inhibits growth in a diverse panel of breast cancer cell lines, causing cell death that involves the p38 stress kinase pathway and a bimodal cell cycle arrest. ERRbeta2 facilitates the block in G2/M, and DY131 delays progression from prophase to anaphase. Finally, ERRbeta2 localizes to centrosomes and DY131 causes mitotic spindle defects. Targeting ERRbeta2 may therefore be a promising therapeutic strategy in breast cancer. PMID- 27363017 TI - Human cytomegalovirus may promote tumour progression by upregulating arginase-2. AB - BACKGROUND: Both arginase (ARG2) and human cytomegalovirus (HCMV) have been implicated in tumorigenesis. However, the role of ARG2 in the pathogenesis of glioblastoma (GBM) and the HCMV effects on ARG2 are unknown. We hypothesize that HCMV may contribute to tumorigenesis by increasing ARG2 expression. RESULTS: ARG2 promotes tumorigenesis by increasing cellular proliferation, migration, invasion and vasculogenic mimicry in GBM cells, at least in part due to overexpression of MMP2/9. The nor-NOHA significantly reduced migration and tube formation of ARG2 overexpressing cells. HCMV immediate-early proteins (IE1/2) or its downstream pathways upregulated the expression of ARG2 in U-251 MG cells. Immunostaining of GBM tissue sections confirmed the overexpression of ARG2, consistent with data from subsets of Gene Expression Omnibus. Moreover, higher levels of ARG2 expression tended to be associated with poorer survival in GBM patient by analyzing data from TCGA. METHODS: The role of ARG2 in tumorigenesis was examined by proliferation-, migration-, invasion-, wound healing- and tube formation assays using an ARG2-overexpressing cell line and ARG inhibitor, N (omega) hydroxy-nor-L-arginine (nor-NOHA) and siRNA against ARG2 coupled with functional assays measuring MMP2/9 activity, VEGF levels and nitric oxide synthase activity. Association between HCMV and ARG2 were examined in vitro with 3 different GBM cell lines, and ex vivo with immunostaining on GBM tissue sections. The viral mechanism mediating ARG2 induction was examined by siRNA approach. Correlation between ARG2 expression and patient survival was extrapolated from bioinformatics analysis on data from The Cancer Genome Atlas (TCGA). CONCLUSIONS: ARG2 promotes tumorigenesis, and HCMV may contribute to GBM pathogenesis by upregulating ARG2. PMID- 27363018 TI - Immunogenic cell death due to a new photodynamic therapy (PDT) with glycoconjugated chlorin (G-chlorin). AB - Both the pre-apoptotic exposure to calreticulin (CRT) and the post-apoptotic release of high-mobility group box 1 protein (HMGB1) are required for immunogenic cell death. Photodynamic therapy (PDT) uses non-toxic photosensitizers and visible light at a specific wavelength in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumor microvasculature, and stimulate the host immune system. We have previously shown that glycoconjugated chlorin (G-chlorin) has superior cancer cell selectivity and effectively suppresses the growth of xenograft tumors. In the present study, we evaluated the immunogenicity of PDT with G-chlorin treatment in colon cancer cells. PDT with G-chlorin suppressed CT26 (mouse colon cancer cells) tumor growth considerably more efficiently in immunocompetent mice (wild-type mice, allograft model) than in immune-deficient mice (nude mice, xenograft model), although control treatments were not different between the two. This treatment also induced CRT translocation and HMGB1 release in cells, as shown by western blot and immunofluorescence staining. To evaluate the use of PDT-treated cells as a tumor vaccine, we employed a syngeneic mouse tumor model (allograft model). Mice inoculated with PDT-treated CT26 cells were significantly protected against a subsequent challenge with live CT26 cells, and this protection was inhibited by siRNA for CRT or HMGB1. In conclusion, PDT with G-chlorin treatment induced immunogenic cell death in a mouse model, where the immunogenicity of this treatment was directed by CRT expression and HMGB1 release. PMID- 27363019 TI - Targeting the WEE1 kinase as a molecular targeted therapy for gastric cancer. AB - Wee1 is a member of the Serine/Threonine protein kinase family and is a key regulator of cell cycle progression. It has been known that WEE1 is highly expressed and has oncogenic functions in various cancers, but it is not yet studied in gastric cancers. In this study, we investigated the oncogenic role and therapeutic potency of targeting WEE1 in gastric cancer. At first, higher expression levels of WEE1 with lower survival probability were determined in stage 4 gastric cancer patients or male patients with accompanied lymph node metastasis. To determine the function of WEE1 in gastric cancer cells, we determined that WEE1 ablation decreased the proliferation, migration, and invasion, while overexpression of WEE1 increased these effects in gastric cancer cells. We also validated the clinical application of WEE1 targeting by a small molecule, AZD1775 (MK-1775), which is a WEE1 specific inhibitor undergoing clinical trials. AZD1775 significantly inhibited cell proliferation and induced apoptosis and cell cycle arrest in gastric cancer cells, which was more effective in WEE1 high-expressing gastric cancer cells. Moreover, we performed combination treatments with AZD1775 and anti-cancer agents, 5- fluorouracil or Paclitaxel in gastric cancer cells and in gastric cancer orthotopic-transplanted mice to maximize the therapeutic effect and safety of AZD1775. The combination treatments dramatically inhibited the proliferation of gastric cancer cells and tumor burdens in stomach orthotopic-transplanted mice. Taken together, we propose that WEE1 is over-expressed and could enhance gastric cancer cell proliferation and metastasis. Therefore, we suggest that WEE1 is a potent target for gastric cancer therapy. PMID- 27363020 TI - Globally increased ultraconserved noncoding RNA expression in pancreatic adenocarcinoma. AB - Transcribed ultraconserved regions (T-UCRs) are a class of non-coding RNAs with 100% sequence conservation among human, rat and mouse genomes. T-UCRs are differentially expressed in several cancers, however their expression in pancreatic adenocarcinoma (PDAC) has not been studied. We used a qPCR array to profile all 481 T-UCRs in pancreatic cancer specimens, pancreatic cancer cell lines, during experimental pancreatic desmoplasia and in the pancreases of P48Cre/wt; KrasLSL-G12D/wt mice. Fourteen, 57 and 29% of the detectable T-UCRs were differentially expressed in the cell lines, human tumors and transgenic mouse pancreases, respectively. The vast majority of the differentially expressed T-UCRs had increased expression in the cancer. T-UCRs were monitored using an in vitro model of the desmoplastic reaction. Twenty-five % of the expressed T-UCRs were increased in the HPDE cells cultured on PANC-1 cellular matrix. UC.190, UC.233 and UC.270 were increased in all three human data sets. siRNA knockdown of each of these three T-UCRs reduced the proliferation of MIA PaCa-2 cells up to 60%. The expression pattern among many T-UCRs in the human and mouse pancreases closely correlated with one another, suggesting that groups of T-UCRs are co activated in PDAC. Successful knockout of the transcription factor EGR1 in PANC-1 cells caused a reduction in the expression of a subset of T-UCRs suggesting that EGR1 may control T-UCR expression in PDAC. We report a global increase in expression of T-UCRs in both human and mouse PDAC. Commonalties in their expression pattern suggest a similar mechanism of transcriptional upregulation for T-UCRs in PDAC. PMID- 27363021 TI - Gene network analysis reveals a novel 22-gene signature of carbon metabolism in hepatocellular carcinoma. AB - Although much progress has been made in understanding cancer cellular metabolism adaptation, the co-regulations between genes of metabolism and cancer pathways and their interactions remain poorly characterized. Here, we applied gene co expression network analysis to 1509 metabolic gene expression data generated from 120 HCC and 180 non-tumor human liver tissues by microarray. Our analyses reveal that metabolism genes can be classified into different co-expression modules based on their associations with HCC related traits. The co-regulation mechanism of the carbon metabolism genes in normal liver tissues was interrupted during the processes of carcinogenesis. In parallel, we performed RNAseq analysis of HCC and non-tumor human liver tissues, and identified a unique 22-carbon-metabolism-gene signature of increased expression. This gene signature was further verified in multiple microarray data sets, and its prognostic value was also proven by HCC patients' survival data from TCGA. Additionally, the tumorigenic function of two representative genes, CS and ACSS1, were validated experimentally by cell growth and spheroid formation assays. The current study provides evidence for the reprogramming of the co-regulation network between carbon metabolism and cancer pathway genes in HCC. In addition, this study also reveals a unique 22-carbon metabolism-gene-expression-signature in HCC. Strategies targeting these genes may represent new therapeutic approaches for HCC treatment. PMID- 27363022 TI - What might explain deprivation-specific differences in the excess hazard of breast cancer death amongst screen-detected women? Analysis of patients diagnosed in the West Midlands region of England from 1989 to 2011. AB - BACKGROUND: Breast cancer survival is higher in less deprived women, even amongst women whose tumor was screen-detected, but reasons behind this have not been comprehensively investigated. METHODS: The excess hazard of breast cancer death in 20,265 women diagnosed with breast cancer, followed up to 2012, was estimated for screen-detected and non-screen-detected women, comparing more deprived to less deprived women using flexible parametric models. Models were adjusted for individual and tumor factors, treatment received and comorbidity. For screen detected women, estimates were also corrected for lead-time and overdiagnosis. RESULTS: The excess hazard ratio (EHR) of breast cancer death in the most deprived group, adjusted only for age and year of diagnosis, was twice that of the least deprived among screen-detected women (EHR=2.12, 95%CI 1.48-2.76) and 64% higher among non-screen-detected women (EHR=1.64, 95%CI 1.41-1.87). Adjustment for stage at diagnosis lowered these estimates by 25%. Further adjustment had little extra impact. In the final models, the excess hazard for the most deprived women was 54% higher (EHR=1.54, 95%CI 1.10-1.98) among screen detected women and 39% higher (EHR=1.39, 95%CI 1.20-1.59) among non-screen detected women. CONCLUSION: A persistent socio-economic gradient in breast cancer related death exists in this cohort, even for screen-detected women. The impact of differential lifestyles, management and treatment warrant further investigation. PMID- 27363023 TI - Docosahexaenoic acid suppresses breast cancer cell metastasis by targeting matrix metalloproteinases. AB - Breast cancer is one of the most prevalent cancers in women, and nearly half of breast cancer patients develop distant metastatic disease after therapy. Despite the significant advances that have been achieved in understanding breast cancer metastasis in the past decades, metastatic cancer is still hard to cure. Here, we demonstrated an anti-cancer mechanism of docosahexaenoic acid (DHA) that suppressed lung metastasis in breast cancer. DHA could inhibit proliferation and invasion of breast cancer cells in vitro, and this was mainly through blocking Cox-2-PGE2-NF-kappaB-MMPs cascades. DHA treatment significantly decreased Cox-2 and NF-kappaB expression as well as nuclear translocation of NF-kappaB in MDA-MB 231 cells. In addition, DHA also reduced NF-kappaB binding to DNA which may lead to inactivation of MMPs. Moreover, in vivo studies using Fat-1 transgenic mice showed remarkable decrease of tumor growth and metastasis to EO771 cells to lung in DHA-rich environment. In conclusion, DHA attenuated breast cancer progression and lung metastasis in part through suppressing MMPs, and these findings suggest chemoprevention and potential therapeutic strategy to overcome malignant breast cancer. PMID- 27363024 TI - Comprehensive analysis of lncRNAs microarray profile and mRNA-lncRNA co expression in oncogenic HPV-positive cervical cancer cell lines. AB - Long non-coding RNAs are emerging to be novel regulators in gene expression. In current study, lncRNAs microarray and lncRNA-mRNA co-expression analysis were performed to explore the alternation and function of lncRNAs in cervical cancer cells. We identified that 4750 lncRNAs (15.52%) were differentially expressed in SiHa (HPV-16 positive) (2127 up-regulated and 2623 down-regulated) compared with C-33A (HPV negative), while 5026 lncRNAs (16.43%) were differentially expressed in HeLa (HPV-18 positive) (2218 up-regulated and 2808 down-regulated) respectively. There were 5008 mRNAs differentially expressed in SiHa and 4993 in HeLa, which were all cataloged by GO terms and KEGG pathway. With the help of mRNA-lncRNA co-expression network, we found that ENST00000503812 was significantly negative correlated with RAD51B and IL-28A expression in SiHa, while ENST00000420168, ENST00000564977 and TCONS_00010232 had significant correlation with FOXQ1 and CASP3 expression in HeLa. Up-regulation of ENST00000503812 may inhibit RAD51B and IL-28A expression and result in deficiency of DNA repair pathway and immune responses in HPV-16 positive cervical cancer cell. Up-regulation of ENST00000420168, ENST00000564977 and down-regulation of TCONS_00010232 might stimulate FOXQ1 expression and suppress CASP3 expression in HPV-18 positive cervical cancer cell, which lead to HPV-induced proliferation and deficiency in apoptosis. These results indicate that changes of lncRNAs and related mRNAs might impact on several cellular pathways and involve in HPV induced proliferation, which enriches our understanding of lncRNAs and coding transcripts anticipated in HPV oncogenesis of cervical cancer. PMID- 27363025 TI - Regression of experimental NIS-expressing breast cancer brain metastases in response to radioiodide/gemcitabine dual therapy. AB - Treating breast cancer brain metastases (BCBMs) is challenging. Na+/I- symporter (NIS) expression in BCBMs would permit their selective targeting with radioiodide (131I-). We show impressive enhancement of tumor response by combining131I- with gemcitabine (GEM), a cytotoxic radiosensitizer. Nude mice mammary fat-pad (MFP) tumors and BCBMs were generated with braintropic MDA-MB-231Br cells transduced with bicistronically-linked NIS and firefly luciferase cDNAs. Response was monitored in vivo via bioluminescent imaging and NIS tumor expression.131I-/GEM therapy inhibited MFP tumor growth more effectively than either agent alone. BCBMs were treated with: high or low-dose GEM (58 or 14.5 mg/Kg*4); 131I- (1mCi or 2*0.5 mCi 7 days apart); and 131I-/GEM therapy. By post-injection day (PID) 25, 82-86% of controls and 78-83% of 131I--treated BCBM grew, whereas 17% low dose and 36% high-dose GEM regressed. The latter tumors were smaller than the controls with comparable NIS expression (~20% of cells). High and low-dose 131I-/ GEM combinations caused 89% and 57% tumor regression, respectively. High-dose GEM/131I- delayed tumor growth: tumors increased 5-fold in size by PID45 (controls by PID18). Although fewer than 25% of cells expressed NIS, GEM/131I- caused dramatic tumor regression in NIS-transduced BCBMs. This effect was synergistic, and supports the hypothesis that GEM radiosensitizes cells to 131I-. PMID- 27363026 TI - Lung cancer exosomes as drivers of epithelial mesenchymal transition. AB - Exosomes, a subgroup of extracellular vesicles (EVs), have been shown to serve as a conduit for the exchange of genetic information between cells. Exosomes are released from all types of cells but in abundance from cancer cells. The contents of exosomes consist of proteins and genetic material (mRNA, DNA and miRNA) from the cell of origin. In this study, we examined the effects of exosomes derived from human lung cancer serum and both highly metastatic and non-metastatic cells on recipient human bronchial epithelial cells (HBECs). We found that exosomes derived from highly metastatic lung cancer cells and human late stage lung cancer serum induced vimentin expression, and epithelial to mesenchymal transition (EMT) in HBECs. Exosomes derived from highly metastatic cancer cells as well as late stage lung cancer serum induce migration, invasion and proliferation in non cancerous recipient cells. Our results suggest that cancer derived exosomes could be a potential mediator of EMT in the recipient cells. PMID- 27363027 TI - Crizotinib inhibits NF2-associated schwannoma through inhibition of focal adhesion kinase 1. AB - Neurofibromatosis type 2 (NF2) is a dominantly inherited autosomal disease characterized by schwannomas of the 8th cranial nerve. The NF2 tumor suppressor gene encodes for Merlin, a protein implicated as a suppressor of multiple cellular signaling pathways. To identify potential drug targets in NF2-associated malignancies we assessed the consequences of inhibiting the tyrosine kinase receptor MET. We identified crizotinib, a MET and ALK inhibitor, as a potent inhibitor of NF2-null Schwann cell proliferation in vitro and tumor growth in vivo. To identify the target/s of crizotnib we employed activity-based protein profiling (ABPP), leading to identification of FAK1 (PTK2) as the relevant target of crizotinib inhibition in NF2-null schwannoma cells. Subsequent studies confirm that inhibition of FAK1 is sufficient to suppress tumorigenesis in animal models of NF2 and that crizotinib-resistant forms of FAK1 can rescue the effects of treatment. These studies identify a FDA approved drug as a potential treatment for NF2 and delineate the mechanism of action in NF2-null Schwann cells. PMID- 27363028 TI - CD147 knockdown improves the antitumor efficacy of trastuzumab in HER2-positive breast cancer cells. AB - Trastuzumab is widely used in the clinical treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer, but the patient response rate is low. CD147 stimulates cancer cell proliferation, migration, metastasis and differentiation and is involved in chemoresistance in many types of cancer cells. Whether CD147 alters the effect of trastuzumab on HER2-positive breast cancer cells has not been previously reported. Our study confirmed that CD147 suppression enhances the effects of trastuzumab both in vitro and in vivo. CD147 suppression increased the inhibitory rate of trastuzumab and cell apoptosis in SKBR3, BT474, HCC1954 and MDA-MB453 cells compared with the controls. Furthermore, CD147 knockdown increased expression of cleaved Caspase-3/9 and poly (ADP-ribose) polymerase (PARP) and decreased both mitogen-activated protein kinase (MAPK) and Akt phosphorylation in the four cell lines. In an HCC1954 xenograft model, trastuzumab achieved greater suppression of tumor growth in the CD147-knockdown group than in the shRNA negative control (NC) group. These data indicated that enhancement of the effect of trastuzumab on HER2-positive cells following CD147 knockdown might be attributed to increased apoptosis and decreased phosphorylation of signaling proteins. CD147 may be a key protein for enhancing the clinical efficacy of trastuzumab. PMID- 27363029 TI - Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas. AB - The current high mortality rate of esophageal adenocarcinoma (EAC) reflects frequent presentation at an advanced stage. Recent efforts utilizing fluorescent peptides have identified overexpressed cell surface targets for endoscopic detection of early stage Barrett's-derived EAC. Unfortunately, 30% of EAC patients present with gastroesophageal junction adenocarcinomas (GEJAC) and lack premalignant Barrett's metaplasia, limiting this early detection strategy. We compared mRNA profiles from 52 EACs (tubular EAC; tEAC) collected above the gastroesophageal junction with 70 GEJACs, 8 normal esophageal and 5 normal gastric mucosa samples. We also analyzed our previously published whole-exome sequencing data in a large cohort of these tumors. Principal component analysis, hierarchical clustering and survival-based analyses demonstrated that GEJAC and tEAC were highly similar, with only modest differences in expression and mutation profiles. The combined expression cohort allowed identification of 49 genes coding cell surface targets overexpressed in both GEJAC and tEAC. We confirmed that three of these candidates (CDH11, ICAM1 and CLDN3) were overexpressed in tumors when compared to normal esophagus, normal gastric and non-dysplastic Barrett's, and localized to the surface of tumor cells. Molecular profiling of tEAC and GEJAC tumors indicated extensive similarity and related molecular processes. Identified genes that encode cell surface proteins overexpressed in both Barrett's-derived EAC and those that arise without Barrett's metaplasia will allow simultaneous detection strategies. PMID- 27363031 TI - Antibody neutralization of cell-surface gC1qR/HABP1/SF2-p32 prevents lamellipodia formation and tumorigenesis. AB - We previously demonstrated that cell-surface gC1qR is a key regulator of lamellipodia formation and cancer metastasis. Here, we screened a monoclonal mouse antibody against gC1qR to prevent cell migration by neutralizing cell surface gC1qR. The anti-gC1qR antibody prevented growth factor-stimulated lamellipodia formation, cell migration and focal adhesion kinase activation by inactivating receptor tyrosine kinases (RTKs) in various cancer cells such as A549, MDA-MB-231, MCF7 and HeLa cells. The antibody neutralization of cell surface gC1qR also inhibited angiogenesis because the anti-gC1qR antibody prevented growth factor-stimulated RTK activation, lamellipodia formation, cell migration and tube formation in HUVEC. In addition, we found that A549 tumorigenesis was reduced in a xenograft mouse model by following the administration of the anti-gC1qR antibody. With these data, we can conclude that the antibody neutralization of cell-surface gC1qR could be a good therapeutic strategy for cancer treatment. PMID- 27363032 TI - Concerted action of IFN-alpha and IFN-lambda induces local NK cell immunity and halts cancer growth. AB - Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer. No significant improvement has been reported with currently available systemic therapies. IFN-alpha has been tested in both clinic and animal models and only moderate benefits have been observed. In animal models, similar modest antitumor efficacy has also been reported for IFN-lambda, a new type of IFN that acts through its own receptor complex. In the present study, the antitumor efficacy of the combination of IFN-alpha and IFN-lambda was tested in the BNL mouse hepatoma model. This study was accomplished by using either engineered tumor cells (IFN alpha/IFN-lambda gene therapy) or by directly injecting tumor-bearing mice with IFN-alpha/IFN-lambda. Both approaches demonstrated that IFN-alpha/IFN-lambda combination therapy was more efficacious than IFN monotherapy based on either IFN alpha or IFN-lambda. In complement to tumor surgery, IFN-alpha/IFN-lambda combination induced complete tumor remission. Highest antitumor efficacy has been obtained following local administration of IFN-alpha/IFN-lambda combination at the tumor site that was associated with strong NK cells tumor infiltration. This supports the use of IFN-alpha/IFN-lambda combination as a new cancer immunotherapy for stimulating antitumor response after cancer surgery. PMID- 27363034 TI - Evidence-Based Review and Discussion Points. PMID- 27363033 TI - Dynein axonemal heavy chain 8 promotes androgen receptor activity and associates with prostate cancer progression. AB - To gain insight into cellular factors regulating AR action that could promote castration resistant prostate cancer (CRPC), we performed a genome-wide RNAi screen for factors that promote ligand-independent AR transcriptional activity and integrated clinical databases for candidate genes that are positively associated with prostate cancer metastasis and recurrence. From this analysis, we identified Dynein Axonemal Heavy Chain 8 (DNAH8) as an AR regulator that displayed higher mRNA expression in metastatic than in primary tumors, and showed high expression in patients with poor prognosis. Axonemal dyneins function in cellular motility, but the function of DNAH8 in prostate cancer or other cell types has not been reported. DNAH8 is on chromosome 6q21.2, a cancer-associated amplicon, and is primarily expressed in prostate and testis. Its expression is higher in primary tumors compared to normal prostate, and is further increased in metastatic prostate cancers. Patients expressing high levels of DNAH8 have a greater risk of relapse and a poor prognosis after prostatectomy. Depletion of DNAH8 in prostate cancer cells suppressed AR transcriptional activity and proliferation. Androgen treatment increased DNAH8 mRNA expression, and AR bound the DNAH8 promoter sequence indicating DNAH8 is an AR target gene. Thus, DNAH8 is a new regulator of AR associated with metastatic tumors and poor prognosis. PMID- 27363035 TI - ASSESSMENT OF THREE BLOOD GENOMIC-DNA PREPARATION METHODS FOR MALARIA MOLECULAR DIAGNOSIS. AB - Species-specific PCR techniques are highly sensitive and reliable alternatives to classical methods for malaria diagnosis and speciation, especially in endemic regions under advanced control or elimination programs where asymptomatic and low density infections are increasingly reported. Nevertheless, the performance of these techniques is directly affected by the quality of isolated DNA templates. A Plasmodium falciparum/vivax-specific diagnostic Nested-PCR (Pf/Pv N-PCR) was used to assess three DNA preparation methods, Qiagen(r) Mini-Chromatographic kit (QIAmp(r)) and Jena-Biosciences(r) DNA isolation kit (JB(r)) for genomic DNA extraction from EDTA-preserved whole blood samples, and Whatman-FTA(r) purification reagent (FTA(r)) for DNA preparation from dry blood spots (DBS) collected onto FTA(r)- cards. A total of 84 out of 137 blood specimens collected from malaria suspicious febrile patients who visited five health care centres in south-western endemic localities of Saudi Arabia were found P. falciparum positive by at least one method. Among these, only 76 (90%) were reported P. falciparum malaria positive by two expert microscopists. No other species of Plasmodium were detected. Pf/Pv N-PCR revealed 84/84 (100%), 75/84 (89%), and 81 (96%) P. falciparum positive samples using DNA templates prepared by QIAmp(r), JB(r), and FTA(r) purification methods, respectively. Therefore, Pf/Pv N-PCR, when applied to QIAmp(r) DNA templates showed to be a highly sensitive diagnostic method, particularly useful for submicroscopic specimens from clinically malaria suspicious patients in endemic areas. On the other hand, Pf/Pv N-PCR of FTA(r) DBS DNA templates revealed 5 positive cases missed by microscopy, encouraging its use as an affordable field semi-adapted protocol for malaria active screening, especially in remqte rural regions with limited laboratory infrastructure. PMID- 27363036 TI - CLINICAL AND PARASITOLOGICAL STUDIES ON PULMONARY AND HEPATIC HYDATID CYSTS IN HOSPITALIZED CHILDREN AND ADULTS. AB - A cross sectional study compared the clinical features of the pulmonary and hepatic hydatid cysts in children and adults and evaluated IHAT and ELISA techniques in diagnosis. The results showed that the patients ages were 5-14 years (10.6 +/- 3.7) in children and 16-75 years (32.2 +/- 14) in adults, patients 34 (75.5%) had liver cysts, 25 (55.5%) had pulmonary cysts and 7 (15.5%) had both liver and lung cysts. In hepatic hydatidosis, 7/34 (20.5%) cases were asymptomatic while others showed variable clinical manifestations. The commonest symptom was localized right hypochondrial pain in 13 (38.2%) and the least one was jaundice in 4 (11.7%). The commonest sign was abdominal masses on the right hypochondrium in 88.2% and the least one was ascites in 5.8%.The commonest symptom of pulmonary hydatidosis was chest pain in 8 (34.7%) followed by cough and hemoptysis pn 4 (17.3%) and the least one was cough and fever (8.6%). Pulmonary hydatid cysts in children were significantly higher in males (17.3%) than females (4.3%), but without significance in adults (26% in male vs. 21.7% in females). Sex difference in hydatid cyst frequencies between adults and children was significant (P < 0.05). Mixed hepatic and pulmonary cysts were less in children than in adults (14.3% vs. 85.7%), with huge pulmonary cysts of 20 cm were more common in children (37.7%) than in adults (17.7%). The high sensitivity (95.5%) of ELISA-IgG recommended this test showed a dependable sero-diagnosing one. PMID- 27363037 TI - IMMUNOTHERAPEUTIC EFFECT OF SPIRAMYCIN IN EXPERIMENTAL GIARDIASIS. AB - Giardiasis is a major global cause of water borne diarrheal disease, which contributes greatly to the burden of malnutrition and malabsorption especially in children. There is a great demand for a new effective therapeutic agent against giardiasis that can be used safely during pregnancy, lactation and in infants. In the present study, the therapeutic effect of spiramycin as well as its immunomodulatory mechanism of action in giardiasis had been investigated. 90 Swiss albino mice were used in this study and classified into 3 groups: GI: 40 mice infected with Giardia lamblia cysts, GII: 40 infected mice that received spiramycin treatment in a daily oral dose of 1000 IU/gm body weight for one week starting one week post infection and GIII: 10 control uninfected untreated mice. 20 mice from each infected group were sacrificed 2 weeks post infection (p.i.) and the remaining mice were sacrificed 4 weeks p.i. Mice of the control groups were sacrificed at one time. The antigiardial therapeutic efficacy of spiramycin was assessed 2 and 4 weeks p.i. by counting of Giardia cysts in stool of mice and studying the histopathological changes and disaccharidase activity in small intestine of mice of different groups. Significant reduction in cysts number shedded in stool of treated animals reached 95.73%. The histopathological changes were mild in all infected groups 2 weeks p.i., while 4 weeks p.i. There was also a significant increase in the number of IELs in treated groups denoting the stimulatory effect of spiramycin on lymphocytic proliferation. On studying the disaccharidase activity, there was significant increase in both sucrase and maltase activities in the treated groups as compared with the nontreated groups. The possible immunomodulatory mechanism of action of spiramycin was studied by measuring the local IgA deposition in small intestinal mucosa by PAP technique 4 weeks p.i. The levels of IgA in small intestine were higher in SP-treated group as compared with the non-treated group. The present results suggested that spiramycin has high efficacy as anti-giardial agent possibly by stimulation of local IgA production. PMID- 27363038 TI - IN VIVO AND IN VITRO EFFICACY OF NIGELLA SATIVA AQUEOUS EXTRACT ON BLASTOCYSTIS HOMINIS. AB - Metronidazole (MTZ) was the most widely accepted treatment for Blastocystis hominis (B. hominis) with high treatment failure rate, resistance and potential mutagenic and carcinogenic effects so there is urgent need to find out new, effective and safe treatment against B. hominis. The present research aimed to evaluate the therapeutic effect of the aqueous extract of Nigella sativa (NS) at different doses on B. hominis in vitro and in vivo in comparison to MTZ as a control drug. Isolates of B. hominis were obtained from patients complaining of diarrhea and abdominal pain. Isolates were cultured in egg diphasic medium (LE) for in vitro study and to adjust proper inoculating dose for in vivo study. The aqueous extract of NS at concentrations of 100 & 500 ug/ml showed a potent lethal effect on B. hominis isolates in vitro. Caecal tissue of experimentally infected and treated mice with two different doses of NS (250 & 500 mg/kg/d) were examined histopathologically and compared with that of mice infected and treated by two doses of MTZ (62 & 125 mg/kg/d) as control drug and Infected untreated mice as negative control group. Histopathological examination of infected untreated group showed all pathological degrees in the caecal tissue while infected treated one showed remission of pathological changes especially with higher dose (500 mg/kg). Present study proved that N. sativa had inhibitory effect on B. hominis in vitro and prevented cytopathic effect in infected mice inoculated orally with B. hominis. PMID- 27363039 TI - MALARIA: A GENERAL MINIREVIEW WITH REFERENCE TO EGYPT. AB - The majority of world's population-live in areas at risk of malaria transmission. Malaria is a serious Anopheles-borne disease that pauses symptoms like the flu, as a high fever, chills, and muscle pain also, anemia, bloody stools, coma, convulsion, fever, headache, jaundice, nausea, sweating and vomiting. Symptoms tend to come and go in cycles. Apart from Anopheles vector, malaria could be transmitted nosocomial, blood transfusion or needle-stick injury Some types of malaria may cause more serious damage problems to heart, lungs, kidneys, or brain. These types can be deadly. The primary factors contributing to the resurgence of malaria are the appearance of drug-resistant strains of the parasite, the spread of insecticide-resistant strains of the mosquito and the lack of licensed malaria vaccines of proven efficacy. In rare cases, people can get malaria if they come into contact with infected blood as in blood transfusion or needle-stick injury also nosocomial and congenital malaria was reported. This is a mini-review of malaria with information on the lethal to humans, Plasmodium falciparum, together with other recent developments in the field. PMID- 27363040 TI - GENETIC POLYMORPHISM OF TOXOPLASMA GONDII FROM RECENTLY INFECTED ABORTED EGYPTIAN WOMEN. AB - Toxoplasmosis caused by Toxoplasma gondii is one of the most prevalent parasitic diseases in human beings. Human toxoplasmosis can be associated with serious clinical manifestations, particularly in developing fetus. The aim of the current study was to identify the possible lineage type of Toxoplasma gondii, molecularly detected in placental samples of women whose pregnancies were spontaneously terminated in the first trimester. Preliminary detection of Toxoplasma genomic materials was done by a SYBR green qPCR technology. Subsequent identification of Toxoplasma strain was done for the positive samples using PCR-restriction fragment length polymorphism (RFLP) at the SAG2 loci of T. gondii using restriction enzymes HhaI and Sau3AI. Out of 72 tested samples, Toxoplasma B1 gene was detected in 9 cases. Toxoplasma genotypes I and II in addition to unknown type were identified in 4, 3 and 2 cases respectively, while type III was not detected in our samples, hence excluded as a leading cause of abortion in humans in our preliminary study. Nevertheless, it remains uncertain to what extent the genotype of the parasite directly contributes to the clinical severity of human toxoplasmosis. Certainly, advanced molecular techniques targeting different Toxoplasma strains are crucial for better understanding of human toxoplasmosis. For more elucidation, additional studies are recommended intended for genetic characterization of such serious parasitic infection using larger number of samples. PMID- 27363041 TI - EFFECT OF LINEZOLID ALONE AND IN COMBINATION WITH OTHER ANTIBIOTICS, ON METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS. AB - The prevalence of methicillin-resistant Staphyloccoccus aureus (MRSA) strains has presented a new challenge in antimicrobial medication. Linezolid is a new drug with potent activity on Gram-positive pathogens such as MRSA. The aim of the study was to investigate the in vitro activity of linezolid alone and in combination with imipenem, vancomycin or rifampicin to determine the most active therapy against MRSA strains. Twenty clinical MRSA strains were isolated from patients admitted to inpatient departments and outpatient clinics of Theodor Bilharz Research Institute. Standard strain MRSA ATCC 43300 was included as a control. The MICs of MRSA strains to linezolid, vancomycin, imipenem and rifampicin were evaluated using E test. Time-kill curve were used to assess the in vitro activity of linezolid (at 8x MIC) alone and in combination with imipenem (at 32x MIC), vancomycin or rifampicin (at 8x MIC). Scanning and transmission electron microscopy were performed to compare bacterial morphological alterations owing to the different combi- nations. Time-kill studies showed synergistic effect when linezolid combined with imipenem was tested against all the MRSA strains. Linezolid plus vancomycin or rifampicin combinations did not display any synergism or antagonism. Scanning and transmission electron microscopy observations confirmed the interactions observed in time kill experiments. Linezolid in combination with subinhibitory concentrations of imipenem can be bactericidal against MRSA strains and appears to be a promising combination for the treatment of MRSA infections. No synergistic activity was seen when the linezolid and vancomycin or rifampicin were combined. Linezolid could prevent the emergence of mutants resistant to rifampicin PMID- 27363042 TI - EGYPTIAN EOSINOPHILIC AND INFECTIOUS MENINGOENCEPHA- LITIS AND THEIR IMPACT ON PSYCHOLOGICAL ASPECTS. AB - Meningoencephalitis is an acute inflammation of the brain and spinal cord & their covering protective membranes. Meningitis can be life-threatening because of the inflammation's proximity to the brain and spinal cord; therefore, the condition is classified as a medical emergency. The commonest symptoms of meningitis are headache and neck stiffness associated with fever, confusion or altered consciousness, vomiting, and an inability to tolerate light (photophobia) or loud noises (phonophobia). Children often exhibit only nonspecific symptoms, such as irritability and drowsiness. If a rash is present, it may indicate a particular cause of meningitis; for instance, meningitis caused by meningococcal bacteria may be accompanied by a characteristic rash. A broad variety of allergic, infectious, neoplastic, and idiopathic diseases are associated with increased blood and/or tissue eosinophilia and range in severity from self-limited conditions to life-threatening disorders. Although accepted upper limits of normal blood eosinophil numbers vary somewhat, a value above 600 eosinophils /microL of blood is abnormal in the vast majority of cases. Generally speaking, there are several possible causes of eosinophils in the CSF; undoubtedly parasitic infection is one of the main causes. PMID- 27363043 TI - HISTOCHEMICAL EFFECTS OF SOME BIOLOGICAL AGENTS ON CULEX PIPIENS LARVAE. AB - The histochemical effects of the lethal concentration that kills 50% of larvae (LC50) of three biological agents, abamectin, Bacillus thuringiensis and spinosad on the carbohydrates (polysaccharides), proteins, nucleic acids and lipids content of the midgut and fat bodies of Culex pipiens 2nd instar larvae were studied. The results showed that the three tested compounds reduced the carbohydrates (polysaccharides), proteins, RNA synthesis and lipids content after 72 hours of treatment where abamectin was the most effective followed by Bacillus thuringiensis then spinosad. PMID- 27363044 TI - MOSQUITO IDENTIFICATION AND MOLECULAR XENOMONITORING OF LYMPHATIC FILARIASIS IN SELECTED ENDEMIC AREAS IN GIZA AND QUALIOUBIYA GOVERNORATES, EGYPT. AB - Lymphatic filariasis is a vector-borne health problem that has been focally endemic in Egypt for centuries. The chief vectors of transmission are Culicinae species. Control measures in the form of mass drug administration of DEC citrate treatment have been implemented in Nile delta for almost a decade. This study aimed to identify the prevalent mosquito species in endemic areas in Giza and Qualioubiya governorates and to monitor Wuchereria bancrofti infection by detecting the parasite DNA in collected mosquitoes. Adult mosquitoes were collected using light traps hung indoors. Microscopic examination was performed to identify and examine the morphologic characters of mosquitoes. Female Culex mosquitoes were subjected to semi-nested PCR to detect filarial DNA targeting repetitive DNA sequences (pWbl2 repetitive region) specific for W. bancrofti. The results revealed 3 species of mosquitoes Culex pipiens, Culex pusillus and Culex quinquefasciatus with the predominance of Culex pipiens (85.7%). Wuchereria bancrofti DNA was not detected in any of the collected mosquito pools. With progress of elimination programme in Nile Delta, follow up studies with larger sample size are recommended as the predominance of Culex pipiens the main lymphatic filariasis vector remains a risk of transmission in such areas. PMID- 27363045 TI - COMPARATIVE STUDY ON IMMUNOBLOT VERSUS PCR IN DIAGNOSIS OF SCHISTOSOMIASIS MANSONI IN EXPERIMENTAL INFECTED MICE. AB - This study compared PCR and Western blot techniques in diagnosis of schistosomiasis mansoni. Forty Swiss albino mice were used, thirty two mice were infected with cercariae of S. mansoni and eight mice were kept uninfected which were used as a control. Blood was obtained from four infected mice weekly beginning from the 1st week to the 8th week post infection. The study found that PCR was positive from the first week post infection, while Western blot technique was positive from the second week post infection. Thus, PCR diagnosed schistosomiasis mansoni earlier than Western blot technique, but both were able to diagnose. PMID- 27363046 TI - ENDOCRINE AND METABOLIC ALTERATIONS MAY UNDERLIE MORTALITY OF SEVERE SEPSIS AND SEPTIC SHOCK PATIENTS ADMITTED TO ICU. AB - The study evaluated endocrinal and metabolic response to sepsis and its applicability for the prediction of outcome of septic patients. Patients were 39 adult with severe infections and within 24 h after onset or suspected clinical tissue hypoperfusion. At enrollment patients were evaluated for acute physiology and chronic health evaluation II score (APACHE II) and Glasgow Coma Scale (GCS). Global hemodynamic parameters including systolic blood pressure (SBP), heart rate (HR) and central venous pressure (CVP) were recorded and monitored. All patients were managed at ICU due to Surviving Sepsis Campaign guidelines. ELISA estimated serum copeptin, macrophage migration inhibitory factor (MIF) and total cortisol (TC) and blood lactate levels. Study outcome was survival rate via 28 days (28-D SR) and best predictor for it. The results showed that 22 patients passed total hospital stay uneventfully for a total survival rate of 56.4%. Seventeen patients died; 10 during ICU stay and 7 during word stay. At admission serum markers levels were significantly higher in survivors and non-survivors compared to controls and in non-survivors compared to survivors. Survival showed negative significant correlation with age, high blood lactate and serum copeptin, TC and MIF levels. Survival showed positive significant correlation with SBP, CVP and urine output. ROC curve and Regression analyses defined high at admission serum copeptin and blood lactate levels as significant predictors for mortality of septic patients. PMID- 27363047 TI - MONOCYTE CHEMOTACTIC PROTEIN AND RESPONSE TO PEGYLATED INTERFERON-ALPHA-2A TREATMENT IN PATIENTS WITH CHRONIC HEPATITIS C (CHC) GENOTYPE 4. AB - The prevalence of hepatitis C virus (HCV) infection varies across the world, with the highest number of infections reported in Egypt. Monocyte chemotactic protein 1 (MCP-1) is a potent chemokine, and its hepatic expression is up-regulated during chronic HCV infection. Fifty naive patients with chronic hepatitis C in National Hepatology & Tropical Medicine Research Institute and 20 healthy volunteers as controls were enrolled in a prospective study designed with strict inclusion criteria to nullify the effect of confounding variables and further minimize selection bias. Fifty naive patients were treated with PEG-IFN-a2b, at a dose of 1801 g/kg subcutaneously every week plus ribavirin at a dose of 1000- 1200 mg/day, according to the patient's body weight, for 48 weeks. Quantification of HCV-RNA by real-time PCR and MCP-1 by ELISA were performed for every patient and controls. There was a sta- tistically significant difference between patients and control group as regards the quantity of MCP-1 (P < 0.05) (Mann-Whitney test) (P = 0.004). There was a significant difference between responders and nonresponses regarding MCP-1 (P < 0.05), responders showed a higher percentage of cases with initial MCP-1 < 306 (P < 0.05). We conclude the importance of the detection of MCP-1 expression at the start of therapy as a factor for assessing the likelihood of HCV genotype 4 patients to achieving a sustained virological response to treatment with IFN-a2 in combination with ribavirin. PMID- 27363048 TI - SERUM MARKERS FOR ASSESSING LIVER FIBROSIS IN EGYPTIAN PA- TIENTS WITH CHRONIC HEPATITIS B AND C CO-INFECTION VERSUS CHRONIC HEPATITIS C. AB - Chronic hepatitis B and C can progress to hepatic fibrosis and cirrhosis. The stage of liver fibrosis is critical for decision of treatment and prediction of outcomes, as life threatening complications highly develop in cirrhotic patients. The aim of this study was to evaluate the diagnostic accuracy of non-invasive serum markers in the assessment of liver fibrosis in patients with combined chronic hepatitis B and C versus those with chronic hepatitis C. This study included 2 groups; Gl: combined chronic hepatitis B & C, which included 71 patients and G2: chronic hepatitis C, which included 70 patients. Liver biopsy results from both groups were recorded. Three validated blood indices Fibro Q, Fibro alpha, and Biotechnology Research Center (BRC) were tested for optimal cut off values for assessing liver fibrosis in both groups. The results showed that the area under receiver operating characteristic curves (AUROC) for Fibro Q in differentiating significant fibrosis (> F2) from non-significant fibrosis (<= F2) was 0.79 (95% CI: 0.60-0.89) in the first group and 0.85 (95% CI: 0.71-0.98) in the second group. AUROC for BRC was 0.76 (95% CI: 0.63-0.89) in the first group and 0.75 (CI: 0.60-0.89) in the second group. Fibro alpha performed less in both groups based on AUROC 0.69 and 0.68 in the first and second group respectively. PMID- 27363049 TI - EFFICACY OF THREE INSECTICIDES ON RAT FLEA (XENOPSYLLA CHEOPIS) INFESTING RODENTS IN GIZA GOVERNORATE, EGYPT. AB - The extensive use of insecticides in public health and agriculture sectors is the main reason for development of resistance in fleas associated in domestic rodents. The present work was planned to investigate the insecticidal efficacy of Lambda-cyhalothrin, Chlorpyrifos and Fenitrothion against rat flea (Xenopsylla cheopis) infesting rodent species in Giza Governorate, Egypt. The lethal concentration Lc50 and Lc90 of population percent were obtained from the established regression log concentrate-response lines. Data indicated that the values of lethal concentration (Lc50) were 0.293, 1.725 & 2.328% for Lambda cyhalothrin, chlorpyrifos and Fenitrothion, respectively. The values of lethal concentration (Lc90) were 0.467, 2.839 & 5.197% for Lambda-cyhalothrin, chlorpyrifos and Fenitrothion, respectively. PMID- 27363050 TI - INHIBITORY ACTIVITY OF PROTECTED EDIBLE PLANTS ON OXIDATIVE STRESS INDUCED BY ORAL 1,4-DIOXANE. AB - 1,4-Dioxane (DX) with two oxygen atoms make it hydrophilic and infinitely soluble in water. As a synthetic organic compound, it used widely throughout industry as a solvent. Dioxane causes numerous human ailments such as liver damage and kidney failure. It has been shown in research to be carcinogenic to animals, and is a potential carcinogen to humans. Daily administration for 1,4-dioxane (100 mg/kg body weight) in drinking water for rats weighing 120 g, except for normal control group. Experimental animal for 42 days was followed through body weight, serum alkaline phosphatase, serum creatinine, malondialdehyde, and catalase enzyme activity; beside histological patterns for liver, kidney, brain and ovary sections. Protection treatment has been offered using oral injection N-acetyl cysteine (100 mg/kg b.wt.), and fresh 200 mg/kg b.wt. in diet meal for each of nabk, husk, and sycamore in separated groups. Body weight and CAT activity have decreased by 25.8, and 68.7%, respectively. While increase has found in MDA, ALP and creatinine values by 76, 48.9, and 67.3%, respectively. NAC showed improvement especially for MDA peroxidation marker and creatinine for kidney disorder. On the other hand, nabk improved CAT activity and husk for ALP liver mutagenicity marker. Intoxicated DX showed edema, kupffer cell activation, atrophy of glomerular tuft, and necrosis of neurons in liver, kidney and brain sections. Obviously nabk showed highly improvement in liver toxicity which is the most sensitive organ to DX as found in research. PMID- 27363051 TI - IDENTIFICATION OF UNDERLYING CAUSES OF CHRONIC UNSPECIFIC UPPER GASTROINTESTINAL RELATED SYMPTOMS IN CHILDREN, A PILOT STUDY. AB - Upper gastrointestinal tract (GIT) symptoms are not disease specific and of limited value in the differentiation of GIT disorders. The present study aimed to determine the etiology of chronic unspecific symptoms in children and to test the need for upper endoscopy in diagnosis. This is a prospective study for 30 Egyptian children presented with chronic upper GIT symptoms for at least 2 months. History regarding severity and frequency of GIT symptoms were asked for. Children with known disorder that explains presenting symptoms were excluded. Upper GIT endoscopy wa performed and 5 biopsies were obtained for pathological examination and for Hpylori testing. The results showed that children age ranged between 2.5-18 years with mean +/- SD of 13.6 +/- 3.4 and 63.3% were females. The main complaints were epigastric pain in 43.3%, hematemesis in 30% and vomiting in 26.7%. Motility disorders were diagnosed in 66.7% children; in the form of GERD in 63.3% and achalasia in one. Complication of GERD in the form of erosive esophagitis was present in 15.8% children, while Barrett's esophagus was not observed. H. pylori infection was diagnosed in 80% histologically. Eosinophilic esophagitis was not detected. PMID- 27363052 TI - SURVEILLANCE OF TRYPANOSOMA SPP OF RODENTS AND STUDIES IN THEIR TRANSMISSION PROBABILITY BY FLEAS IN SOME RURAL EGYPTIAN AREAS. AB - A new public health problem arises from animal trypanosomes that afflict human by a disease called atypical human trypanosomiasis. Although humans have an innate protection against most Trypanosoma species, nineteen cases of atypical human trypanosomiasis caused by the animal trypanosome as T. b. brucei, T. vivax, T. congolense, T. evansi and T. lewisi have been recorded. Some of theserecorded cases were transient, six required trypanocidal treatments however two patients died. Rodent trypanosome, T. lewisi is transmitted via ingestion of fleas or their feces containing the infective stage, the metacyclic trypomastigote. Because of the high densities of various species of rodents and their distribution all over the country especially in rural areas, the present work aimed to evaluate the trypanosomiasis among rodents collected from November to March 2016 and study transmission probability by their fleas in some rural areas in Abu Alnomros Center, Giza. The overall trypanosomiasis prevalence among the different rodent species was (21 rats) 24.7%. All the infected rats belonged to Rattus r. spp where the prevalence of infection with Trypanosoma lewisi among that species was very high 51.2% while none of rats belonged to Rattus norvegicus were infected. That may be attributed to the solid immunity gained by the R. norvegicus where most of the collected norvegicus were aged and weighed more than 200 grams. There was an inverse significant correlation between the densities of parasites and the weights of the losts. The rat which recorded the highest parasite density (60,000 parasites/microliter) was a female Rattus r. captured indoor (inside house). As to sex of Rattus rattus spp no significant difference was found between males and females in trypanosomiasis. Also there was no significant correlation between the densities of parasites and the number of white blood cells among Rattus rattus spp. All positive rats were collected indoors (from houses) and all the rats which were captured from outdoors (farms) were negative for T. lewisi. The difference between infections with trypanosomiasis among rats inhabited the houses and that found in farms was highly significant. Only two species of fleas were found on rats, Xenopsylla cheopis and Leptopsylla segnis. The oriental fleas, X cheopis, were found mainly on R. norvegicus where 57.5% of R. norvegicus were positive for X cheopis while only one rat was positive for L. segnis. On other hand the rat fleas, L. segnis, were found mainly on Rattus rattus spp where 39% of these rats were positive for L. segnis. The present work revealed a significant correlation between the infection with T. lewisi, and the presence of L. segnis on the rats however that correlation regarding X. cheopis was not significant. PMID- 27363053 TI - INTERVENTION PROGRAM FOR NURSING STAFF REGARDING APPROACH TO A PATIENT WITH SPIDER PHOBIA AND/OR BITE. AB - Spider bites are uncommon medical events, since there are limited number of spiders world-wide with fangs strong enough to pierce human skin, and most spiders bite humans only as a final defense when being crushed between skin and another object. Thus, most lesions attributed to spider bites are caused by some other etiology. The spiders that can cause medically significant bites include widow and false widow spiders (worldwide), recluse spiders (mostly North and South America), Australian funnel web spiders (eastern coastal Australia) and Phoneutria spiders (Brazil). Acute spider bites most commonly result in a solitary papule, pustule, or wheal. Systemic symptoms can accompany envenomation of widow; funnel web, and Phoneutria spiders, and less often, those of recluse spiders. PMID- 27363054 TI - ANTIMICROBIAL ACTIVITY FOR EXCRETION AND SECRETION OF THE GREENBOTTLE FLY LARVAE LUCILIA SERICATA (MEIGEN) (DIPTERA: CALLIPHORIDAE). AB - Sterile larval excretion/secretion (ES) exhibited antibacterial activity against some species of bacteria. They were shown to inhibit the growth of Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis Gram-negative bacteria Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae and Fungi Geotricum candidum and Aspergillus fumigatus thus exhibited limited inhibitory effect towards Gram-positive bacteria Streptococcus pyogenes and Staphylococcus epidermidis and Gram-negative Proteous vulgaris and Fungi Syncephalastrum racemosum, Candida albicans, that effect was slowed down when challenged with secretion on a solid media but no zone of complete inhibition was detectqd. Growth inhibiting activity was determined in liquid growth media using the Gram positive, Gram-negative bacterial and fungal strains as indicator organisms. PMID- 27363055 TI - THE EFFICACY OF THREE MEDICINAL PLANTS; GARLIC, GINGER AND MIRAZID AND A CHEMICAL DRUG METRONIDAZOLE AGAINST CRYPTOSPORIDIUM PARVUM: II-HISTOLOGICAL CHANGES. AB - Cryptosporidiosis parvum is a zoonotic protozoan parasite infects intestinal epithelial cells of man and animals causing a major health problem. This study was oriented to evaluate the protective and curative capacity of garlic, ginger and mirazid in comparison with metronidazole drug (commercially known) against Cryptosporidium in experimental mice. Male Swiss Albino mice experimentally infected with C. parvum were treated with medicinal plants extracts (Ginger, Mirazid, and Garlic) as compared to chemical drug Metronidazole. Importantly, C. parvum-infected mice treated with ginger, Mirazid, garlic and metronidazole showed a complete elimination in shedding oocysts by 9th day PI. The reduction and elimination of shedding oocysts in response to the treatments might be attributable to a direct effect on parasite growth in intestines, sexual phases production and/or the formation of oocysts. The results were evaluated histopathological examination of ideum section of control mice (uninfected, untreated) displayed normal architecture of the villi. Examiination of infected mice ileum section (infected, untreated) displayed histopathological alterations from uninfected groups. Examination of ileum section prepared from mice treated with garlic, ginger, mirazid, and metronidazole displayed histopathological alterations from that of the control groups, and showed marked histologic correction in the pattern with the four regimes used in comparison to control mice. Garlic successfully eradicated oocysts of infected mice from stool and intestine. Supplementation of ginger to infected mice markedly corrected elevation in the inflammatory risk factors and implied its potential antioxidant, anti-inflammatory and immunomodulatory capabilities. Infected mice treated with ginger, mirazid, garlic and metronidazole showed significant symptomatic improvements during treatment. PMID- 27363056 TI - APPRAISAL OF PRENATAL ANTI-TOXOPLASMA GONDII (IGG+IGM)- IHA/IGM-ELISA SCREENING IN SINGLE SAMPLES VIA IGG AVIDITY TEST. AB - Congenital toxoplasmosis is associated with important morbidity and mortality. Since vertical transmission of Toxoplasma gondii can occur in acute cases, antenatal screening for recent infections is vital. Accurate determination of acute toxoplasmosis requires a combination of immunoassays, usually not routinely applied for screening purposes. This study evaluated the anti-T. gondii (IgG+IgM)/IgM prenatal screening procedure by IgG avidity assay. The routine prenatal screening for (IgG+IgM) anti-T. gondii by indirect hemagglutination (IHA) in serum samples was done of 2247 pregnant women who attended two hospitals between 2011 and 2013 revealed 487 (21.7%) positive samples. Examination of IHA positive sera by IgM and IgG/IgG-avidity concurrent ELISA tests revealed 7 positive and 3 border-line IgM-ELISA titers during the initial check-up of 10 women, who were then followed up at 3-4 week-intervals. Among these, 4 (40%) showed simultaneous high avidity IgG antibodies, indicating distant infection by the parasite, and no anti-T. gondii specific IgG could be detected in follow-up sera of two cases (20%), indicating false IgM initial positive results. Only 4 (40%) women showed simultaneous IgM and low avidity IgG antibodies indicating active infections. Avoidance of an over-diagnosis of acute toxoplasmosis Anti-T. gondii (IgG+IgM)/IgM prenatal screening must be supplemented by a discriminative test like IgG avidity ELISA. PMID- 27363057 TI - STUDIES ON AEDES AEGYPTI RESISTANCE TO SOME INSECTICIDES IN THE JAZAN DISTRICT, SAUDI ARABIA. AB - The present study provided information on the susceptibility status of the adult and larvae of Aedes aegypti mosquitoes in Jazan region of Saudi Arabia. Bioassay tests were performed on adults and larvae by using WHO recommended concentrations and test kits. Adults of Ae. aegypti mosquitoes were exposed to test papers impregnated with Lambda-cyhalothrin (0.05%), Cyfluthrin (0.15%), Deltamethrin (0.05%), Permethrin (0.75%), Fenitrothion (1%), Bendiocarb (0.1%) and DDT (4%) insecticides. Ae. aegypti mosquitoes were found to be susceptible only to Cyfluthrin; (mortality rate was 100%), whereas variable resistances were observed from the rest of the other insecticides tested (mortality rates ranged between 93.6 and 17%). Larvae were subjected to different concentrations of Diflubenzuron, Methoprene (IGRs) and Temephos (Organophosphate). Adult emergence inhibition (IE50 & IE95) values for the IGRs and the (LC50 & LC95) for Temephos were determined by log-probit regression analysis. Ae. aegypti larvae were resistant to Temephos (LC50 61.8-LC95 35600.1 mg/l) and showed high susceptibility to Methoprene than Diflubenzuron (IE50 0.49-IE95 10.9 mg/l) and (IE50 0.86 and IE95 93.8 mg/l), respectively. Larvae were more susceptible to Methoprene than Diflubenzuron by 1.8 folds. PMID- 27363058 TI - LYMPHO-PROLIFERATIVE RESPONSES TO VARIOUS FASCIOLA HEPATICA WORM'S ANTIGENS: AN IN VITRO STUDY. AB - Fascioliasis is an important zoonotic disease with approximately 2-4 million people infected worldwide and a further 180 million at risk of infection. F. hepatica can survive within the bile ducts for many years through its ability to suppress the host immunity with Fasciola cathepsin L1 cysteine protease and Glutathione S transferase playing an important role. The aim of the present study is to investigate the in vitro lympho-proliferative responses of hepatic hilar lymphocytes (HLN) of infected sheep in response to different F. hepatica antigens. The suppressive effects of Fasciola excretory/secretory (ES) and tegument (TEG) and their fractions were also investigated. Our results showed that both ES and TEG had significant suppressive effects on lympho-proliferation, up to 74% and 92%, respectively. When these antigens were fractionated, fraction 3 (MW of >10000-30000) of both ES (64%) and TEG (59%) in addition to fraction 4 (MW of <= 10000) of TEG (38%) inherited the suppressive effects. Identification of the potential molecule(s) with such suppressive effects on lymphocytes in TEG fraction 4 could reveal vaccine candidates. PMID- 27363059 TI - MAGGOT DEBRIDEMENT THERAPY (MDT): IT IS SAFE AND ECONOMIC FOR TREATING A DIABETIC FOOT ULCER. AB - Diabetic foot ulcer (DFU) is the major global and devastating complication of diabetes mellitus that affects at least 20% of diabetic patients during their lifetime. This article presents an overview of the research evidence on maggot debridement therapy that serves as a guide to health professionals who may be users of this form of treatment now and in the future. It is a time to apply this sample and safe worldwide approved method for diabetic foot ulcer to save money and avoid surgical intervention. PMID- 27363060 TI - Value of p16(INK4a) and Ki-67 Immunohistochemical Staining in Cervical Intraepithelial Neoplasia Grade 2 Biopsies as Biomarkers for Cervical Intraepithelial Neoplasia Grade 3 in Cone Results. AB - OBJECTIVE: To evaluate the usefulness of p16(INK4a) (p16) and Ki-67 staining in high-grade cervical intraepithelial neoplasia (CIN2) biopsies in order to predict CIN3 results in cone specimens, thereby sparing those not likely at risk for CIN3 from unnecessary cone excision. STUDY DESIGN: We retrospectively recruited patients with CIN2 colposcopy-directed biopsy treated by loop electrosurgical excision procedure. The expression of p16 and Ki-67 was qualitatively and quantitatively analyzed in all biopsies and cone specimens. RESULTS: A total of 123 patients from January 2009 to December 2010 were included in the study. CIN3 in cone specimens was observed in 35 patients (28.5%). Ki-67 positive immunostaining in > 50% of epithelial cells was related to CIN3 diagnoses in cone specimens (p = 0.043). However, p16+ and Ki-67+ evaluated by thirds of the epithelial thickness in CIN2 biopsies did not show a significant correlation with the cone results. In multivariate analysis, Ki-67 cell expression over 50% in CIN2 biopsies and high-grade squamous intraepithelial lesion (HSIL) in the previous cytology were statistically associated with CIN3 results in the cone (odds ratio [OR] 2.55, 95% confidence interval [CI] 1.04-6.29; OR 2.68, 95% CI 1.07-6.72, respectively). CONCLUSION: Patients with HSIL in the previous cytology and Ki-67 cell expression over 50% in their CIN2 biopsies could be considered in need of treatment by cone for their higher risk of underlying CIN3 lesions. PMID- 27363061 TI - Significance of Number and Localization of Positive Core Biopsies for the Identification of Prostate Cancer Eligible for Active Surveillance. AB - OBJECTIVE: Prostate cancer (PCa) patients fulfilling the Epstein criteria for insignificant disease are eligible for the treatment option of active surveillance (AS). Using the combined histological and cytological grading (Gleason/Helpap score), we aimed to investigate the significance of biopsy localization and tumor involvement in core needle biopsies as discriminators for insignificant cancer. STUDY DESIGN: Primary prostate biopsies of 1,285 patients were analyzed by the combined histological and cytological grading with regard to biopsy localization and tumor involvement per core. For patients diagnosed with pT2a stage PCa, core needle biopsies were further compared with the corresponding radical prostatectomy (RP) specimens. RESULTS: According to the combined histological and cytological grading, 95% of low-grade PCas (Gleason score 6/2a, prognostic grading group I) presented with a tumor involvement of < 10% in 1 core biopsy, whereas intermediate-grade tumors (prognostic grading group 2) displayed dissimilar tumor localization in 1 or both lobes with higher tumor volume. CONCLUSION: Our results indicate that the combined Gleason/Helpap grading may contribute to a more reliable identification of insignificant PCa with the option of AS. Ancillary criteria include the limitation of tumor involvement to < 10% per core, localized in 1 or 2 adjacent biopsies in only 1 lobe. Under this presupposition, > 90% of insignificant carcinomas concurred with low-grade PCa and stage pT2a tumors with negative margins after RP. PMID- 27363062 TI - Effects of Nicotine on Rat Tongue Mucosa. Histopathological and Immunohistochemical Analyses. AB - OBJECTIVE: To evaluate the histopathological and immunohistochemical effects of systemically administered nicotine on rat tongue mucosa. STUDY DESIGN: Rats were assigned to one of two groups: the experimental group received nicotine systemically (nicotine sulphate 2 mg/kg subcutaneously daily for 28 days), while the rats in the control group were administered physiological saline (1.5 mL subcutaneously for 28 days). All animals were sacrificed at the end of the study, and tongue tissue samples were removed and prepared according to routine histological procedures. Sections were stained with hematoxylin and eosin and observed by light microscopy. Immunoreactivity of tongue mucosa was assessed with E-cadherin, collagen IV, and VEGF expression by immunohistochemical staining. RESULTS: There were significant differences in the average histopathological score between the nicotine-treated and untreated groups. Morphological changes, including inflammatory leukocyte infiltration and cellular desquamation, blood vessel dilation, hemorrhage, and epithelial degeneration, were noted. Further, E cadherin expression was significantly decreased in the nicotine-treated group versus the untreated group. The nicotine treatment group showed an increase in collagen IV secondary papillae and basal cells. CONCLUSION: The increased level of VEGF expression in the nicotine-treated group may have affected endothelial cell apoptosis. PMID- 27363063 TI - Prognostic Significance of Mitotic Activity in Noninvasive, Low-Grade, Papillary Urothelial Carcinoma. AB - OBJECTIVE: To identify the most useful method to detect the mitotic count (MC) by comparing different techniques, to determine a cutoff value for mitotic activity (MA), and to evaluate the correlation of this value with the recurrence of noninvasive low-grade papillary urothelial neoplasm (LGPUC). STUDY DESIGN: Hematoxylin and eosin-stained slides of 55 LGPUC cases were evaluated for their MA. MC was determined using 4 different methods. In Method 1, cases with 3 mitoses in 1 single focus of a high-power field (HPF x 400) were found, and in Method 2, cases with >= 5 mitoses in 1 singlefocus of an HPF, in any level of the neoplastic epithelium, were determined. The areas with the highest MA values in the lower third and those with the highest MA values in the upper two-thirds of the neoplastic epithelium were marked in Methods 3 and 4, respectively. Then, mitotic figures were counted in these fields, and cases with 5 mitoses were determined. RESULTS: In the recurrent group the number of cases with >= 5 mitoses, as detected by Methods 2 and 4, was significantly higher than that found for the nonrecurrent group (p = 0.0001 and p = 0.002, respectively). The number of mitoses, as detected by Methods 1 and 3, was not significantly different between the groups. CONCLUSION: We suggest that determining MC may be used as a prognostic marker to predict LGPUC recurrence and that the mitotic numbers should be included in the initial pathology report to guide the clinician in patient management. PMID- 27363064 TI - High Incidence of Incidental Prostate Cancer in Transurethral Resection of Prostate Specimens in China. The Value of Pathologic Review. AB - OBJECTIVE: To identify the incidence and clinicopathologic features of prostate cancer incidentally detected in patients undergoing transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH), and to estimate the clinical value of pathologic review of all TURP specimens. STUDY DESIGN: A pathologic review was performed on all TURP specimens for each patient from May 1, 2004, to June 30, 2014, in our institute. A total of 1,024 men (ages 46-98) were identified by pathology specimen. Those with a known diagnosis of prostate cancer prior to TURP (n = 16) were excluded from the analysis. The tumor volume, Gleason score, pathologic stage, serum prostate-specific antigen (PSA) level, and follow-up data were evaluated for those who were found to have prostate cancer. RESULTS: A total of 87 (8.6%) patients (ages 50-88) were found to have prostate cancer. Significant prostate cancer was found in 25 patients. From May 1, 2004, to May 31, 2009, 30 (6.1%) patients (ages 57-83) were found to have prostate cancer. From June 1, 2009, to June 30, 2014, 57 (11.0%) patients (ages 50-88) were found to have prostate cancer. CONCLUSION: Our series demonstrates that 8.6% of patients were found to have prostate cancer and that the incidence was increasing in recent years. Even in some patients with T1a disease, the tumors were significant. The pathologic review of TURP specimens is valuable in China. PMID- 27363065 TI - Diagnostic Value of Urine Cytology in Bladder Cancer. A Meta-Analysis. AB - OBJECTIVE: To evaluate the diagnostic value of urine cytology in detecting bladder cancer using meta-analysis. STUDY DESIGN: Public databases, including PubMed, Embase, Springer, Elsevier Science Direct, Cochrane Library, and Google Scholar, were searched before February 2015. Sensitivity, specificity, positive likelihood ratio (LR), negative LR, and diagnostic odds ratio (DOR) of urine cytology in individual studies were calculated using random effects model or fixed effect model. The summary receiver operating characteristic (SROC) curve was applied for performance of urine cytology. Publication bias of the included studies was evaluated by Egger's test. RESULTS: A total of 17 separate studies consisting of 5,908 patients with bladder cancer were included in the meta analysis. Significant heterogeneity between the studies (I2 = 98.6%, p < 0.01) and effect sizes were pooled using random effects model. Overall sensitivity, specificity, positive LR, negative LR, and DOR of urine cytology were 0.37 (95% CI 0.35-0.39), 0.95 (95% CI 0.94-0.95), 7.39 (95% CI 4.97-10.98), 0.56 (95% CI 0.47-0.68), and 15.76 (95% CI 9.03-27.50), respectively. The area under the curve (AUC) and Q* index were 0.80 and 0.74, respectively. No publication bias was observed (p = 0.12). CONCLUSION: Our data indicate that urine cytology might be more suitable as an assistant method in bladder cancer detection by combining with other diagnostic methods with high sensitivity. PMID- 27363066 TI - Role of Quercetin in Cadmium-Induced Oxidative Stress, Testicular Damage, and Apoptosis in Rats. AB - OBJECTIVE: The aim of this study was to investigate the role of quercetin on cadmium-induced oxidative stress, testicular damage, and apoptosis in rat testes. STUDY DESIGN: The rats were randomly allotted into 1 of 3 experimental groups: control, cadmium-treated, and cadmium-treated with quercetin; each group con- tained 10 animals. Control animals received daily injec- tions of the saline vehicle alone. The cadmium-treated group was injected subcutaneously with cadmium chloride (CdCl2) dissolved in saline at a dose of 2 mL/kg/ day for 30 days, resulting in a dosage of 1 mg/kg cadmium. The rats in quercetin-treated groups were given quercetin (15 mg/kg body weight) once a day i.p., starting 2 days prior to the cadmium injection during the study period. All animals were sacrificed and testes tissues were removed for histopathological and biochemical (malondialdehyde [MDA], superoxide dismutase [SOD], glutathione peroxidase [GSH Px], and serum testosterone levels) investigation. RESULTS: The mean seminiferous tubule diameter, Johnsen's mean testicular biopsy score values, biochemical parameters (MDA, SOD, GSH-Px, and serum testosterone levels), and amount of germ cell apoptosis were significantly decreased in the cadmium-treated groups as compared to the control group. Furthermore, the quercetin-treated animals showed improved histological and biochemical parameters in the cadmium-treated group. CONCLUSION: The present study showed that quercetin treatment protected testes against toxic effects of cadmium. We believe that further preclinical research into the utility of quercetin may indicate its usefulness as a potential treatment for spermatogenesis after testicular injury caused by cadmium-treated rats. PMID- 27363067 TI - Inverted Papilloma of the Bladder Coexisting with Urothelial Carcinoma. A Case Report. AB - BACKGROUND: Inverted papilloma (IP) is an unusual benign neoplasm, most commonly found in the bladder. Cases of malignant transformation have been reported in the past, although most of them are now considered to be urothelial carcinomas with an inverted growth pattern. CASE: A 54-year-old man was diagnosed with urothelial carcinoma in situ (UCIS), high-grade papillary urothelial carcinoma (HGPUC), and IP by transurethral resection specimen of the bladder. The urothelial carcinoma cells were seen colonizing the inverted papilloma. CONCLUSION: The coexistence of IP with UCIS and HGPUC is rare. Immunohistochemistry helps distinguish between IP and UC in difficult cases such as this one. A brief review of other reported cases of inverted papilloma coexisting with urothelial carcinoma in the English literature over the past 25 years is presented. PMID- 27363068 TI - Another Case of Multifocal Blue Nevus of the Prostate. PMID- 27363069 TI - Thank You to the Government. PMID- 27363070 TI - May I Ethically Discontinue Treating An Overanxious Patient? PMID- 27363071 TI - Second MOM-n-PA Event a Huge Success in Allentown. PMID- 27363072 TI - MOM-n-PA Volunteers Change Lives. More Than 2,000 People Treated at Allentown's Agri-Pex. PMID- 27363073 TI - Clinicopathologic Review: Recurrent Gingival Lesion. Diagnosis: Pyogenic granuloma. PMID- 27363074 TI - Another Day, Another Dollar ... or maybe just 96 cents! PMID- 27363075 TI - 10 HIPAA mistakes practices must avoid. PMID- 27363077 TI - TRUMP vs. HILLARY. The showdown physicians want. PMID- 27363076 TI - The MOC revolt, part 2: Alternative board fights for relevancy. PMID- 27363078 TI - Understand the new diabetes code for primary care. PMID- 27363079 TI - How physicians can determine life insurance needs. PMID- 27363080 TI - Telemedicine empowers patients, but challenges physicians. PMID- 27363082 TI - Don't expect legislative defenses against cyberattacks anytime soon. PMID- 27363081 TI - THE RISE OF DIRECT PRIMARY CARE. PMID- 27363083 TI - CONNECTING THE DOTS ON CANCER. PMID- 27363084 TI - THE FIGHT TO DOMINATE BIG PHARMA(CY). PMID- 27363086 TI - 87th Annual PHYSICIAN REPORT. The return of optimism in medical practice. PMID- 27363085 TI - HACKER BAD BOY VENTURE CAPITALIST DISRUPTER HEALER. PMID- 27363087 TI - 87th Annual PHYSICIAN REPORT. SALARY. PMID- 27363088 TI - Why Medicare wants to compare your coding to other doctors. PMID- 27363089 TI - Prepare now for value-based pay. PMID- 27363090 TI - Five ways to boost your practice's online reputation. PMID- 27363091 TI - Take control of OSHA compliance. PMID- 27363092 TI - ACOs of the future: How the model is changing. PMID- 27363093 TI - Making mobile apps useful for physicians. PMID- 27363095 TI - Physicians face stark choices under new Medicare pay proposal. PMID- 27363094 TI - Maintenance of certification pushed me out of medicine. PMID- 27363096 TI - How Medicare's payment overhaul tries to change how docs use tech. PMID- 27363097 TI - The striking variation of commercial healthcare prices. PMID- 27363098 TI - Major Medicaid managed-care reforms hand the ball to states. Will they run with it? PMID- 27363099 TI - Medicaid's unmanaged managed care. PMID- 27363100 TI - THE VIRTUAL DOCTOR WILL SEE YOU NOW. PMID- 27363101 TI - Better oversight for Medicaid; a questionable start on doc pay. PMID- 27363102 TI - Advance care planning plays essential role in a truly patient-centered healthcare system. PMID- 27363103 TI - Navigating data via machine learning. PMID- 27363104 TI - 'Drug prices are the wrong target'. PMID- 27363105 TI - Preventing malpractice lawsuits due to EHR errors. PMID- 27363106 TI - The population health CHALLENGE. Closing care gaps for better outcomes. PMID- 27363107 TI - Population health's impact on private practice. PMID- 27363108 TI - Capturing chronic care revenue requires IT infrastructure. PMID- 27363109 TI - Physician-assisted suicide up for debate in states. PMID- 27363110 TI - Understanding medical necessity and how it controls your payment. PMID- 27363111 TI - Surviving the transition from independent to employed. PMID- 27363112 TI - What government auditors are focusing on this year. PMID- 27363113 TI - Do you need malpractice tail coverage? PMID- 27363114 TI - Building strong physician-manager teams. PMID- 27363115 TI - Choosing the best physician disability insurance policy. PMID- 27363116 TI - Government, payers working to streamline quality measures. PMID- 27363117 TI - What UnitedHealth's retreat says about the ACA marketplaces. PMID- 27363118 TI - CMS squeezes hospitals on pay. PMID- 27363119 TI - Merger indigestion. PMID- 27363120 TI - Top health systems cultivate culture of transparency. PMID- 27363121 TI - Healthcare alone won't reverse the coming longevity decline. PMID- 27363123 TI - 'We're trying to build the business case for achieving health equity'. PMID- 27363122 TI - We can't lose focus on quality in the pursuit of value in healthcare. PMID- 27363124 TI - [Risk Assessment and Risk Management of Chemicals in China]. AB - Risk assessment and risk management have been increasingly approved as an effective approach for appropriate disposal and scientific management of chemicals. This study systematically analyzed the risk assessment methods of chemicals from three aspects including health risk, ecological risk and regional risk. Based on the current situation of classification and management towards chemicals in China, a specific framework of risk management on chemicals was proposed by selecting target chemicals, predominant industries and related stakeholders as the objects. The results of the present study will provide scientific support for improving risk assessment and reasonable management of chemicals in China. PMID- 27363125 TI - [Application of Land-use Regression Models in Spatial-temporal Differentiation of Air Pollution]. AB - With the rapid development of urbanization, industrialization and motorization, air pollution has become one of the most serious environmental problems in our country, which has negative impacts on public health and ecological environment. LUR model is one of the common methods simulating spatial-temporal differentiation of air pollution at city scale. It has broad application in Europe and North America, but not really in China. Based on many studies at home and abroad, this study started with the main steps to develop LUR model, including obtaining the monitoring data, generating variables, developing models, model validation and regression mapping. Then a conclusion was drawn on the progress of LUR models in spatial-temporal differentiation of air pollution. Furthermore, the research focus and orientation in the future were prospected, including highlighting spatial-temporal differentiation, increasing classes of model variables and improving the methods of model development. This paper was aimed to popularize the application of LUR model in China, and provide a methodological basis for human exposure, epidemiologic study and health risk assessment. PMID- 27363126 TI - [Ecological Footprint Evolution Characteristics and Its Influencing Factors in China from 2000 to 2010]. AB - According to global average land productivities in 2000, this study calculated ecological footprint (EF) in China from 2000 to 2010, and analyzed its dynamic characteristics and socio-economic driving forces. The results showed that the total EF in China increased from 1.769 to 3.259 billion global hectares (gha) from 2000 to 2010, and its annual growth rate was 6.30%. Carbon Footprint was the fastest growth type of EF. It increased from 0.742 to 1.805 billion gha, and its annual growth rate was 9.29%. The net increase of cropland Footprint was also large in comparison to other types of Footprint. It increased from 0.678 to 0.891 billion gha. Per capita EF in China increased from 1.40 to 2.43 gha in this period. Although it was still below the world average level, it was far beyond per capita ecological carrying capacity in China, which led to serious ecological deficit and severe ecological crisis in China. The fast growth of per capita EF was the main driving force for the growth of total EF in China during the study period. Further, the growth of per capita EF was positively influenced by the growth of per capita consumption of products and severs, which was driven by economic growth and urbanization. Meanwhile, a large amount of exports of resource-intensive products in international trade was also an important driving force for EF growth. According to the evolution route of per capita EF in developed countries, along with China moving from middle-income to high-income country, per capita EF will maintain rapid growth, and ecological deficit in China will further exacerbate. PMID- 27363127 TI - [Pollution Characteristics and Sources of Carbonaceous Aerosol in PM2.5 During Winter in Guanzhong Area]. AB - To study the characteristics and sources of carbonaceous aerosol in PM2.5 during winter in Guanzhong area, PM2.5 samples were collected from December 2012 to February 2013 in Xi'an, Baoji, Weinan and Qinling, and then organic carbon (OC) and elemental carbon (EC) were analyzed following the thermal/optical reflection protocol. The average concentrations of OC in the four sites were 47.8, 45.8, 31.2 and 37.0 microg x m(-3), respectively, while EC concentrations were 8.5, 6.7, 7.6 and 5.7 microg x m(-3), respectively. Total carbonaceous aerosol (TCA) accounted for 36.4%, 46.2%, 36.9% and 33.4% of PM2.5, respectively. OC was strongly correlated with EC in Xi'an (R2 = 0.93) and Qinling (R2 = 0.91), while weakly correlated in Baoji (R2 = 0.58) and Weinan (R2 = 0.62), which indicated that OC and EC had more similar sources or higher mixing degree in the former two sites. All OC/EC ratios exceeded 2.0, which indicated the formation of secondary organic carbon (SOC). In Xi'an, Baoji, Weinan and Qinling, SOC accounted for 21.6%, 40.3%, 23.2% and 27.8% of OC, respectively. Positive matrix factorization (PMF) was used to analyze the sources of carbonaceous aerosol and four sources were obtained. Coal burning was the major source, contributing 45.3%-47.9% in Guanzhong area. Gasoline vehicle and biomass burning were the minor sources, contributing 26.1%-33.1% and 14.3%-20.1% respectively. In addition, diesel vehicle also had some contribution to carbonaceous aerosol. PMID- 27363128 TI - [Chemical Composition of the Single Particle Aerosol in Winter in Nanning Using SPAMS]. AB - Single Particle Aerosol Mass Spectrometry (SPAMS) was performed to characterize the PM2.5 in Nanning from 15 to 24 February 2015. The correlation (R2) between the PM2.5 number concentration and the mass concentration of PM2.5 obtained using SPAMS was 0.76. The particle number concentration could reflect the atmospheric pollution situation to some degree. The Art-2a classification method was used to classify the chemical composition of PM2.5. The results showed that the principal chemical constituents were elemental carbon, organic elements carbon hybrid particles, organic carbon, rich potassium particles, mineral substance, rich sodium particles, second inorganic particles, levoglucosan and other heavy metals. Among them, the composition of elemental carbon was the highest, followed by organic carbon and rich potassium particles. The particle size of 80% of PM2.5 was mainly concentrated in the range of 0.2 microm to 1.0 microm with a peak value occurring at 0. 62 microm. The particle size distribution characteristics of different chemical components were similar. The number concentration of the chemical components in PM2.5 had the same variation tread with the mass concentration of PM2.5 over time. To a certain extent, the change in chemical composition could reflect the instantaneous pollution source. PMID- 27363129 TI - [Correlation Analysis Between Characteristics of VOCs and Ozone Formation Potential in Summer in Nanjing Urban District]. AB - Volatile organic compounds (VOCs) is an important precursor of photochemical ozone pollution (O3) in the atmosphere. Their concentration variation directly affects the characteristics of the ozone pollution. The concentration, speciation of VOCs, ozone and its precursors in Nanjing were analyzed and measured using online gas detection systems in August 2013. VOCs/NOx discriminant method was used to get the sensitive control factors of ozone. The results showed that the averaged volume fraction of VOCs was 52. 05 x 10(-9), and the largest one reached 200 x 10(-9) in Nanjing urban district. The order of volume fraction of each species VOCs was alkane > oxygen-containing VOCs > alkene > aromatics. The averaged concentration of ozone was 76.5 microg x m(-1) and the exceeding concentration of hourly standard was 5.9%. The change trends of ozone precursors VOCs and NOx were basically identical and Ozone showed the obvious negative correlation during the period of high concentrations of ozone. There were some differences in the concentrations of the same VOCs in different ozone concentration periods. The ozone generation in Nanjing urban district was sensitive to VOCs, and Nanjing belonged to VOCs control area in summer. PMID- 27363130 TI - [Seasonal Dynamics of Airborne Pollens and Its Relationship with Meteorological Factors in Beijing Urban Area]. AB - The seasonal dynamics of airborne pollens and their relationship with meteorological conditions, which are considered to be important factors for appropriate construction of urban green system and reliable prevention of tropic pollinosis, were investigated in Beijing urban area. The airborne pollens were monitored from December 31st 2011 to December 31st 2012 by Burkard volumetric trap, and the data were analyzed. The results revealed that: (1) In 2012 the pollen dispersion period lasted 238 days from March 17 to November 18th, accounting for 65% of the year. There were two peaks of pollen amount in air, which occurred from March to May and from August to October, respectively. In the spring peak, tree pollens such as Oleaceae, Populus and Salix pollens were the dominant, accounting for 53% of the total annual pollens, while in the autumn period, weed pollens such as Compositae, Chenopodiaceae and Amaranthaceae pollens made up about 40% of the annual total value; (2) The highly allergenic weeds pollens dominated in autumn, which caused a high incidence of tropic pollinosis; (3) The airborne pollen amount of Beijing urban area was significantly affected by meteorological condition like the wind speed, temperature, humidity, precipitation and so on; (4) When temperature ranged from OC to 15 degrees C, the pollen amount showed positive relation with temperature; while in the temperature range of 18 degrees C to 30 degrees C, it showed negative relation; (5) The average temperature of spring and autumn season in 2012 was 17 degrees C, and 79% of airborne pollens were detected in these two seasons. This temperature condition was conducive to the pollen dispersion. (6) The pollen amount showed negative relation with relative moisture between 20% and 50% and larger than 70%, while in the moisture range of 50% to 60%, it showed positive relation; (7) The wind speed smaller than 3 m x s(-1) was good to pollen distribution, when it was larger than 4 m x s(-1) or the wind lasted for a long time, the pollen amount in the air would decrease; (8) The pollen release was decreased by the rain. The above results can be helpful to forecast the pollen amount in the air. monitoring; pollen amount PMID- 27363131 TI - [Mercury Distribution Characteristics and Atmospheric Mercury Emission Factors of Typical Waste Incineration Plants in Chongqing]. AB - Waste incineration is one of the important atmospheric mercury emission sources. The aim of this article is to explore the atmospheric mercury pollution level of waste incineration industry from Chongqing. This study investigated the mercury emissions from a municipal solid waste incineration plant and a medical waste incineration plant in Chongqing. The exhaust gas samples in these two incineration plants were obtained using USA EPA 30B method. The mercury concentrations in the fly ash and bottom ash samples were analyzed. The results indicated that the mercury concentrations of the municipal solid waste and medical waste incineration plant in Chongqing were (26.4 +/- 22.7) microg x m(-3) and (3.1 +/- 0.8) microg x m(-3) in exhaust gas respectively, (5279.2 +/- 798.0) microg x kg(-1) and (11,709.5 +/- 460.5) microg x kg(-1) in fly ash respectively. Besides, the distribution proportions of the mercury content from municipal solid waste and medical waste in exhaust gas, fly ash, and bottom ash were 34.0%, 65.3%, 0.7% and 32.3%, 67.5%, 0.2% respectively; The mercury removal efficiencies of municipal solid waste and medical waste incineration plants were 66.0% and 67.7% respectively. The atmospheric mercury emission factors of municipal solid waste and medical waste incineration plants were (126.7 +/- 109.0) microg x kg( 1) and (46.5 +/- 12.0) microg x kg(-1) respectively. Compared with domestic municipal solid waste incineration plants in the Pearl River Delta region, the atmospheric mercury emission factor of municipal solid waste incineration plant in Chongqing was lower. PMID- 27363132 TI - [Characteristics of Atmospheric Dry and Wet Deposition of Trace Metals in the Hinterland of the Three Gorges Reservoir, China]. AB - In order to investigate the characteristics of atmospheric trace metals deposition in the hinterland of the Three Gorges Reservoir, the wet and dry deposition samples were collected at an urban area sampling site in Wanzhou during January to June 2014. Besides, the samples were collected at five other sampling sites in April 2014 for comparative analysis, including factory region, town suburb, nature reserve, county suburb, and rural area. pH, conductivity, and trace metals (Al, As, B, Ba, Bi, Cd, Co, Cr, Cu, Fe, Li, Mn, Pb, Ni, Sb, Sr, Sn, Ti, Zn, V) were analyzed. In urban area, the acid rain frequency was 48.44% , and the acid rain occurred mainly in the period of January to April. The order of acid rain frequency in various functional areas was factory region > urban area > county suburb > town suburb > nature reserve > county rural area. All of the trace metals in wet deposition during the sampling period were lower than the National Environmental Quality Standard for Surface Water Standard of Class III. Cd, Cu, Ph and Zn were found exceeding the standard of class I , and the pollution in factory region was more serious compared to other functional areas. The extract pH of dry deposition in urban area was in the range of 4.91-6.74, with an average value of 5.79. The order of dry deposition in various functional areas was factory region > county suburb > urban area > county rural area > town suburb > nature reserve, which was exactly the same as that of the wet deposition, indicating the similar sources of dry and wet deposition. In urban area, the contents of Ba, Co, Cu, Cr, Li, Mn, Ni, Sr, Zn in dry deposition were greater than those in wet deposition, but the contents of Al, As, B, Bi, Cd, Fe, Ph, Sb, Sn, Ti, V showed the opposite trend. Analysis of the enrichment factors showed that Al was in moderate enrichment, while Bi and Cd were significantly enriched. PMID- 27363133 TI - [Monitoring and Analysis of Stable Isotopes of the Near Surface Water Vapor in Changsha]. AB - Based on the monitored atmospheric water vapor stable isotopes and observed meteorological elements at Changsha during the period from November 12, 2014 to April 13, 2015, the variations of water vapor stable isotopes and the relationships between isotope ratios and temperature, absolute humidity, precipitation amount were analyzed in this paper. The results indicated that: (1) Seasonal variations of delta18O and 82H in atmospheric water vapor at Changsha were remarkable, with high values in winter. delta18O and delta2H in atmospheric water vapor were positively correlated with absolute humidity in winter. There were some fluctuations of the delta18O and delta2H in atmospheric water vapor, especially when the precipitation events occurred. Precipitation events had a significant effect on the variations of delta18O and delta2H in atmospheric water vapor, and low values were often accompanied with precipitation events; (2) Diurnal Variations of delta18O and delta2H in atmospheric water vapor had a close correlation with the atmospheric water vapor content, whereas the absolute humidity was mainly controlled by the strength of the local evapotranspiration and atmospheric turbulence. The "precipitation amount effect" was observed during the process of a single precipitation event; (3) Values of delta18O and delta2H in atmospheric water vapor were always lower than those of precipitation in Changsha, but he variation trends were completely consistent, the average difference values were 8.6% per hundred and 66.82% per hundred, respectively; (4) The meteoric vapor line (MVL) in cold months was delta2H =7.18 delta18O + 10.58, the slope and intercept of MVL were always lower than those of MWL, and the slope and intercept of MVL in spring were significantly higher than those of winter. PMID- 27363134 TI - [Mercury Transport from Glacier to Runoff in Typical Inland Glacial Area in the Tibetan Plateau]. AB - To investigate the transport of mercury from glacier to runoff in typical inland glacial area in the Tibetan Plateau, we selected Zhadang glacier and Qugaqie river Basin located in the Nyainqentanglha Range region and collected samples from snow pit, glacier melt-water and Qugaqie river water during 15th August to 9'h September 2011. Mercury speciation and concentrations were determined and their distribution and controlling factors in different environmental compartments were analyzed. The results showed that the average THg concentrations were (3.79 +/- 5.12) ng x L(-1), (1.06 +/- 0.77) ng x L(-1) and (1.02 +/- 0.24) ng x L(-1) for glacier snow, glacier melt-water and Qugaqie river water, respectively, all of which were at the global background levels. Particulate-bound mercury accounted for large proportion of mercury in all environmental matrices, while mercury in glacial melt-water was controlled by total suspended particle, and mercury in Qugaqie river water co-varied with runoff. With the increase of temperature, glacier melted and released water as well as mercury into glacier-fed river. Total mercury concentrations in glacier melt water, upstream and downstream peaked at 14:00, 16:00 and after 20:00, respectively, reflecting the process of mercury release from glacier and its subsequent transport in the glacier fed river. The transport of riverine mercury was controlled by multiple factors. Under the context of climate change, glacier ablation and the increasing runoff will play increasingly important roles in mercury release and transport. PMID- 27363135 TI - [Characteristics and Risk Assessment of Heavy Metals in Core Sediments from Lakes of Tibet]. AB - To explore the source of heavy metals in lake sediments and their hazard to environment on Tibetan Plateau, China, heavy metal (Cu, Zn, Cd, Pb, Cr, Co, Ni and As) levels in surface sediments of 18 lakes were investigated. Inductively Coupled Plasma Mass Spectrometry (ICP-MS, X-7 series) was used to determine the contents of heavy metals and the concentrations of carbon and nitrogen in sediment samples were analyzed by element analyzer (Vario Max CN, Elementar, Germany). The average concentrations for Cu, Zn, Cd, Pb, Cr, Co, Ni and As were 24.61 mg x kg(-1), 70.14 mg x kg(-1), 0.26 mg x kg(-1), 25.43 mg x kg(-1), 74.12 mg x kg(-1), 7.93 mg x kg(-1), 33.85 mg x kg(-1), 77.69 mg x kg(-1). It was found that heavy-metal concentrations in Tibet sediments were higher than those in Antarctic, but lower than those in the regions affected by anthropogenic activities. The contents of Cu, Zn, Pb, Cr and Co in the samples were lower than the background values of Tibet. Correlation analysis and principal components analysis (PCA) were used to analyze the origins of heavy metals. The result showed that Cu, Zn, Cd, Pb, Co, Ni and As came from soil in drainage basin and atmospheric deposition. Cr was mainly affected by human activities. Assessment on ecological risk of heavy metals was carried out using Hakanson's method and cluster analysis (CA). Assessment on ecological risk indicated that Pumoyum Co, Longmo Co and Bangong Co were at low risks, Bieruoze Co was at high ecological risk level and the other lakes were at different risk levels. PMID- 27363136 TI - [Distribution and Potential Ecological Risk Assessment of Heavy Metals in Surface Sediments of Inflow Rivers to Northeastern Lake Tanganyika]. AB - As the second deepest lake in Africa, Lake Tanganyika plays an important role in supplying fish protein for citizens in the catchment. However, the lake is increasingly threatened by environmental pollution with the development of social economy and expanding of population. In order to reveal the external source of heavy metals in Lake Tanganyika, 16 surface sediment samples from the rivers which flow into the northeast of the lake were collected and analyzed. Besides the contents, the potential ecological risk indices (RI) of each heavy metal were also analyzed. Furthermore, the relationship, between land use and the spatial distribution of heavy metals was also discussed. The average contents of Cu, Zn, Cd, Pb and Hg were 18. 4, 21.2, 0.05, 6.6 mg x kg(-1) and 8.4 ng x g(-1), respectively, with the maximum values of Zn, Pb and Cd located in Bujumbura urban rivers. The data indicated that all the inflow rivers were at low potential ecological risk. RI of heavy metals ranked as the following order: Cd > Hg > Cu > Pb > Zn, as Cd being the key element contributing to the risk. The relationship between land use and heavy metals showed that the contents of heavy metals were highest in urban areas, followed by estuarine wetlands, and woodlands were least polluted by heavy metals. This distribution type implied that human activities could cause the heavy metal accumulation in the surface sediments of nearby rivers. The urban areas and estuarine wetlands need to be concerned in the further study. PMID- 27363137 TI - [Over One Hundred Year Sediment Record of Polycyclic Aromatic Hydrocarbons in the Lake Bosten, Xinjiang]. AB - The vertical distributions of 16 polycyclic aromatic hydrocarbons (PAHs) were investigated from a sediment core in the Lake Bosten, Xinjiang. Meanwhile, the possible source and risk assessment of PAHs in Lake Bosten were also discussed. The total PAHs concentration in the sediment core ranged from 37.5 ng x g(-1) to 184.5 ng x g(-1), and Naphthalene and Phenanthrene were the dominant compounds throughout the core. Over the one hundred year, the vertical profile of PAHs underwent significant changes around 1950s. The vertical distributions of PAHs had little change and low molecular weight PAHs were dominant PAHs before 1950s. Since then, the high molecular weight PAHs appeared and increased with fluctuations. A sharp increase in PAHs level and individuals was observed especially after 1990s and a maximum was found in the surface sediment. The results suggested PAHs in Lake Bosten were from the local sources, which were dominated by the low temperature combustion. Besides, the abundance of PAHs from high temperature combustion processes, such as combustion of industrial coal and vehicle emission, increased significantly in recent years. However, based on the results of risk assessment, the PAHs may not induce adverse biological effects on the aquatic ecosystem in Lake Bosten. PMID- 27363138 TI - [Distribution Characteristics of Polycyclic Aromatic Hydrocarbons in Different Environmental Media from Qingbang Island, Zhoushan, China]. AB - Eleven soil, three seawater and three passive air samples were collected from Qingbang Island in July, 2013, and 16 polycyclic aromatic hydrocarbons (PAHs) were analyzed. The distribution characteristics, possible sources and ecological risk assessment were investigated. The results showed that the concentrations of total 16 PAHs ranged between 60.30 and 123.34 ng x g(-1) with a mean value of 105.49 ng x g(-1) in soil, 45.96-101.08 ng x L(-1) with a mean value of 66.45 ng x L(-1) in seawater and 5.09-5.41 ng x d(-1) with a mean value of 5.35 ng x d(-1) in air samples, respectively. The PAHls concentrations of soil samples in tidal zone were higher than those in other areas. The highest PAHs concentrations in seawater were detected in complicated hydrological sea area. PAHs concentrations in air were equally distributed around the island. 2-4 rings PAHs were dominant species in soil, water and air samples. Ratio method and factor analysis were used to identify the possible sources of PAHs. The result suggested that PAHs in soil were mainly originated from combustion of coal, wood, diesel and petrol, while the possible sources of PAHls in water and air were mixed. The ecological risk assessment indicated that PAi s in different environment media posed little risk to people. PMID- 27363139 TI - [Transformation of Non-point Source Soluble Nitrogen in Simulated Drainage Ditch]. AB - The drainage ditch has a compound ecosystem structure consisting of water, sediment and plants. Migration and transformation of the non-point source solute is important to study interception, control and management of agricultural non point source pollution in the drainage ditch. Based on the experiment on static simulation of drainage ditches, the article used typical non-point source soluble nitrogen as an example to analyze the changing process of nitrogen content in water, sediment and reeds, and to study the effects of the sediment adsorption and desorption, reeds growth and death in different periods on nitrogen concentration in water. The article discussed nitrogen migration in water sediment-reeds compound ecosystem and its influence on nitrogen concentration in water. The results showed that both adsorption and desorption in sediment and absorption and assimilation of reeds growth had effect on nitrogen concentration in water. The effect before October was reducing the nitrogen concentration in water, which was the process of nitrogen purification in water. After October, the nitrogen concentration in water increased and made it easy to form secondary nitrogen pollution. Meanwhile, the migration in the water-sediment-seeds ecosystem in simulated drainage ditch had close ties, any migration and transformation of nitrogen in a single medium or between different mediums would cause adjustment of nitrogen concentration in water. PMID- 27363140 TI - [Influence of Landscape Heterogeneity on Total Nitrogen Concentration in Zhongtian River Watershed]. AB - Nutrient loading into rivers is generally changed by human-induced land use changes and can lead to surface water quality changes. Understanding the extent to which landscape heterogeneity influences nutrient loading is critical to the development of best management practices aimed at water-quality improvement. In this study, the year-round concentrations of total nitrogen were monitored from January 2013 to December 2013 in the 20 hydrological stations of Zhongtian River. Considering the nested relationship of watershed unit, seven land use structures and 13 landscape pattern indexes were chosen, and Pearson correlation analysis, principal component analysis and multiple regression analysis were used to explore the effects of land use pattern on total nitrogen concentrations in Zhongtian River. The results showed that: (1) Construction land and grasslands had a significant impact on total nitrogen concentration, construction land would worsen the water quality, while grasslands could improve water quality; (2) Landscape patch- shape index, landscape patch-area index and construction land were the main factors affecting the total nitrogen concentration in landscape scale; (3) Regression analysis showed that the construction land and landscape patch-area index contributions to total nitrogen concentrations were 67.31% and 32.69%, respectively. PMID- 27363141 TI - [Nitrogen Release from Sediment Under Dry and Rainy Season Alternation and Its Contribution to N Export from Xiangxi Watershed in Jiangxi Province]. AB - In this study, N export from Xiangxi River Basin in Qianyanzhou station was measured by long-term monitoring, and simulation study on N. release law from the sediment in watershed was carried out based on orthogonal experiment, and at last the contributions of N release from sediment to N transport from watershed under dry and rainy season alternation were estimated. The results showed that the maximum of TN release rate was 36 mg x (m2 x d)(-1) in stable status, which decreased with increasing time; the impact of the three controlling factors on the N release followed the order of temperature > disturbance > pH, and the effect of temperature and pH on N release from the sediment was significant when disturbance was considered as the error term; TN release rate increased with increase of temperature, and acidic and alkaline conditions could also promote N release from sediment, wherein the effect of acidic conditions on N release was stronger; the changes of TN and available N content in sediment were 414.7-899.6 mg x kg(-1) and 17.5-58.9 mg x kg(-1), so the percentage of available N only accounted for 3%-10% of TN; the TN transport concentrations were 0.58-2.40 mg x L(-1) and 1.73-4.87 mg x L(-1) in dry and wet seasons, respectively, the N release flux from sediment was about 106.34 kg x a(-1), the total N transport from watershed was 864.15 kg x a(-1), and the contribution rate of N release from sediment to N transport from watershed was about 12.31%, so we should pay much attention to the contribution of N release from sediment to water eutrophication. PMID- 27363142 TI - [Spatial and Temporal Distributions of Nitrogen and Phosphate in the Chaohu Lake]. AB - In order to determine the concentrations, spatial and temporal distributions of nitrogen ( N) and phosphorus (P) nutrients in Chaohu Lake, the surface water samples were collected systemically in different flood seasons by grid sampling methods. Meanwhile, the predominant pollution factors and priority control area were confirmed. The results showed that the concentrations of TP, TN and NO3- -N in the inflowing rivers were higher than the V class water standard, the concentrations of nutrients in wet season were lower than those in normal season and dry season in Nanfei River and Shiwuli River, while the levels of nutrients in the other selected rivers were higher in wet season. The variations of spatial and temporal of nutrients were observed in the Chaohu Lake. The concentrations of N and P nutrients in the western part of Chaohu Lake were higher than those of the eastern part. The elevated concentrations of TP, TN and NH4+ -N were found in the dry season, while the elevated content of NO3- -N was observed in the wet season. The predominant pollution factors in Chaohu Lake were TN and NH4+ -N, the concentrations of these nutrients were decreasing from the western part of the Chaohu Lake to the eastern part of the Chaohu Lake. PMID- 27363143 TI - [Phosphorus Fractions and Release Risk in Surface Sediments of an Agricultural Headwater Stream System in Hefei Suburban, China]. AB - A typical water system of agricultural headwater stream in Chaohu Lake basin was selected as the study area, and 17, 16, 14 and 13 surface sediments were collected from the four styles of stream, respectively, including ponds, branches, main channel and mainstream deep pools, in October 2014 (in autumn) and April 2015 (in spring). The forms and space-time variations of phosphorus in the sediments were analyzed. Clustering and variance analysis were conducted on the phosphorus forms data from the four styles of stream by means of multivariate statistical analyses. We quantified the phosphorus release risk (PSI) and identified the main impact factors of PSI via calculating the phosphorus sorption index (PSI) and the correlation analysis. The results showed that: (1) The contents of TP in the surface sediments ranged from 137.517 to 1709.229 mg x kg( 1) with an average value of 532. 245 mg x kg(-1), and the order of the average contents of phosphorus forms was IP (350.347 mg x kg(-1)) > OP (167.333 mg x kg( 1)) > Fe/Al-P ( 78. 869 mg x kg(-1)) > Ca-P (56.343 mg x kg(-1)) > Ex-P (6.609 mg x kg(-1)); (2) The contents of phosphorus forms had the same trend in all the four stream styles, which was deep pool > main channel > branch > pond; (3) In autumn, the deep pool and main channel were clustered into one class, while the pond and branch were clustered into the other class. In spring, branch, main channel and deep pool were clustered into the same class; (4) Variance analysis showed that the differences among the four stream styles were larger in autumn than in spring; (5) The PSI of the surface sediments ranged between 24.49 and 69.94 (mg x L(-1) x (100 g x micromol)(-1). The PSI in spring was lower than that in spring, indicating that phosphorus release risk of surface sediment was higher in spring than in autumn. (6) PSI had a significant negative correlation with Ex P, IP and pH. PMID- 27363144 TI - [Surface Property and Sorption Characteristics of Phosphorus onto Surface Sediments in Sanggou Bay]. AB - Kinetic curves and isotherms were investigated to study the sorption mechanism of phosphorus onto the sediments of Sanggou Bay, together with the surface charge properties of sediments and the forms of phosphorus studied. The results showed that the sorption including a fast process and a slow one, and could be described by a two-compartment first order equation. The thermodynamic isotherms were well fitted with a modified Langmuir equation. The maximum adsorption capacity was larger in summer than in spring, and the smaller particle size was favorable to the sorption. The maximum adsorption capacities (Qm) were 0.0471-0.1230 mg x g( 1), and the zero equilibrium phosphorus concentration (EPC0) of the sediments ranged from 0.0596 mg x L(-1) to 0.1927 mg x L(-1), which indicated that the sediments from Sanggou Bay were sources of phosphorus. Inorganic phosphorus (IP) was the main form of total phosphorus (TP). The contents of exchangeable or loosely absorbed P and Fe-bound P increased significantly in the samples after sorption. The sorption process involved physical sorption and chemical sorption, with the former being the predominant. PMID- 27363145 TI - [Particle Size Distribution and Pollutant Speciation Analyses of Stormwater Runoff in the Ancient Town of Suzhou]. AB - The particle size distribution (PSD) and its transformation processes in the stormwater runoffs in the ancient town of Suzhou were studied based on the particles size analyses, the water-quality monitoring data and the parameters of the rainfall-runoff models. The commercial districts, the modern residential area, the old residential area, the traffic area and the landscape tourist area were selected as the five functional example areas in the ancient town of Suzhou. The effects of antecedent dry period, the rainfall intensity and the amount of runoffs on the particle size distributions were studied, and the existing forms of the main pollutants in different functional areas and their possible relations were analyzed as well. The results showed that the particle size distribution, the migration processes and the output characteristics in the stormwater runoffs were greatly different in these five functional areas, which indicated different control measures for the pollution of the runoffs should be taken in the design process. The antecedent dry period, the rainfall intensity and the amount of runoffs showed significant correlations with the particle size distribution, showing these were the important factors. The output of the particles was greatly influenced by the flow scouring in the early period of the rainfall, and the correlations between the amount of runoffs and the particle migration ability presented significant difference in 30% (early period) and 70% (later period) of the runoff volume. The major existence form of the output pollutants was particle, and the correlation analyses of different diameter particles showed that the particles smaller than 150 microm were the dominant carrier of the pollutants via adsorption and accumulation processes. PMID- 27363146 TI - [Abundance of Toxic and Non-toxic Microcystis sp. in Lake Hongze and Its Correlation with Environmental Factors]. AB - In the present study, the eutrophic level of 30 water samples collected from Lake hongze in August 2014 were analyzed, and the abundance of toxic and non-toxic Microcystis sp., together with their spatial distribution, was investigated by quantitative real-time PCR techniques. The results showed that the average concentrations of total nitrogen and total phosphorus were 1.63 and 0.11 mg x L( 1), respectively. The trophic state index ( TSI) ranged from 58.1 to 73.6, and the water quality was in the state of eutrophication based on TSI. Toxic Microcystis was widely distributed in Lake Hongze, and its abundance varied sharply, from 1. 13 x 10(4) to 3.51 x 10(6) copies x mL(-1), and the abundance of total Microcystis ranged from 1.06 x 10(5) to 1.10 x 10(7) copies x m(-1), meanwhile, the proportion of toxic Microcystis in the total Microcystis ranged from 8.5% to 38.5%, with the average value of 23.6%. Correlation analysis indicated that there was a significant positive correlation among total Mirocystis, toxic Microcystis and the toxic proportion (P < 0.01). The abundance of total and toxic Microcystis was significantly positively correlated to chlorophyll a ( Chl-a) concentrations and TSI (P < 0.01), but was negatively correlated to transparency (SD) (P < 0.01). The ratio of toxic Microcystis to total Microcystis was significantly positively correlated to Chl-a, TN, TP and TSI (P < 0.01), but significantly negatively correlated to the ratio of TN to TP and SD (P < 0.01). Therefore, reducing total nitrogen and phosphorus concentrations could not only lower the eutrophication level of Lake Hongze, but also inhibit the competition advantage of the toxic Microcystis over non-toxic Microcystis. PMID- 27363147 TI - [Effect of Charge-Transfer Complex on Ultraviolet-Visible (UV-Vis) Absorption Property of Chromophoric Dissolved Organic Matter (CDOM) in Waters of Typical Water-Level Fluctuation Zones of the Three Gorges Reservoir Areas]. AB - As an important fraction of dissolved organic matter (DOM), chromophoric dissolved organic matter (CDOM) plays a key role in decision of the optical properties and photogeochemistry of DOM, and further affects pollutant fate and global carbon cycle. These optical properties are ascribed to two chromophoric systems including superposition of individual chromophores and charge-transfer (CT) complexation between electron donor (e.g., phenols and indoles) and acceptor (e.g., quinones and other oxidized aromatics) in DOM structures. Thus in this study, based on the "double-chromophoric system" model, DOM samples from four typical water-level fluctuation zones of Three Gorges Reservoir (TGR) areas were selected, to investigate the effect and contribution of charge-transfer complex to ultraviolet-visible (UV-Vis) absorption property of CDOM. Using NaBH, reduction method, original featureless absorption curve was classified into two independent curves caused by individual chromophoric group, which were derived from a simple superposition of independent chromophore and charge-transfer complex, respectively. Also, the changes in curve properties and specific parameters before and after NaBH4 reduction were compared. The results showed that in all DOM samples from the four sites of TGR, more than 35% of absorption was attributed from CT complex. Shibaozhai of Zhongxian and Zhenxi of Fuling showed the highest proportion ( > 50%). It suggested that the role of CT complex in CDOM property could not be neglected. After removal of CT complex, absorption curve showed blue-shift and CDOM concentration [a (355)] decreased significantly. Meanwhile, because of deforming of bonds by reduction, DOM structures became more dispersive and the molecular size was decreased, resulting in the lower spectral slope (S) observed, which evidentially supported that the supermolecular association structure of DOM was self-assembled through CT complex. Meanwhile, deceasing hydrophobic components led to decreased apparent aromaticity (lower SUVA values), whereas specific parameters including SUVA, CDOM and SR still were applicable for comparison among different DOM samples instead of the same sample without consideration of "double-cbromopboric system" model involving tbe role of CT complex. Comparatively, S(275-295) was dynamic due to tbe impact of CT effect. Furtbermore, establisbing DOC estimation model by short-wavelength range of CDOM was recommended because of its stability despite of CT complex. PMID- 27363148 TI - [Influence of pH on Kinetics of Anilines Oxidation by Permanganate]. AB - To investigate the effect of pH on the oxidation of anilines by potassium permanganate, aniline and p-Chloroaniline were taken as the target contaminants, and the experiments were conducted under the condition with potassium permanganate in excess over a wide pH range. The reaction displayed remarkable autocatalysis, which was presumably ascribed to the formation of complexes by the in situ generated MnOx and the target contaminants on its surface, and thereby improved the oxidation rate of the target contaminants by permanganate. The reaction kinetics was fitted with the pseudo-first-order kinetics at different pH to obtain the pseudo-first-order reaction constants (k(obs)). The second-order rate constants calculated from permanganate concentration and k,b, increased with the increase of pH and reached the maximum near their respective pKa, after which they decreased gradually. This tendency is called parabola-like shaped pH-rate profile. The second-order rate constants between permanganate and anilines were well fitted by the proton transfer model proposed by us in previous work. PMID- 27363149 TI - [Effects of EDTA on the Reductive Dechlorination of 2,4-D by Pd/Fe]. AB - In Pd/Fe system, zero-valent iron (ZVI) passivation layer is easily formed on the particle surface during the catalytic reductive dechlorination of chlorinated organics, hindering further dechlorination of target contaminants. In this paper, the passivation layer on the Pd/Fe particle surfaces could be eliminated by the chelation of disodium edetate (EDTA) with Fe2+, Fe3+, making the reductive dechlorination continue. The experiment investigated the effects of EDTA addition manner and dosage, pH, Pd loading and temperature on dechlorination of 2,4 dichlorophenoxyacetic acid (2,4-D) by Pd/Fe. The conclusions can be summarized as follows: (1) Phenoxyacetic acid (PA) generation ratio reached 90. 7% within 20 min with EDTA concentration of 25.0 mmol x L(-1) and flow rate of 20 mL x h(-1), while it was only 74.5% after 210 min in the system without EDTA. (2) The EDTA could chelate the Fe2+ and Fe3+ generated from the process of 2,4-D dechlorination by Pd/Fe, preventing or slowing down the formation of passivation layer, and accelerating the reduction efficiency. (3) The appropriate experimental parameters for 2,4-D removal were as follows: EDTA flow rate of 20 mL x h(-1), CEDTA of 25.0 mmol x L(-1), Pd loading of 0.050%, 200 r x min(-1), pH 4.2 and 30.0 degrees C. The removal percentage of 20.0 mg x L(-1) 2,4-D reached nearly up to 100% within 210 min under these conditions. (4) The intermediates of 2, 4-D catalytic dechlorination included 2-chlorophenoxvacetic acid (2-CPA) and trace 4-chloronhenoxyacetic acid (4-CPA), and the end product was PA. PMID- 27363150 TI - [Preparation of NiAl-MMO Films Electrode and Its Capacitive Deionization Property]. AB - Hydrotalcites are not only considered as important absorbents in water treatment and but also widely used as super capacitor materials. In this study, NiAl metal oxide (NiAl-MMO) films, which were the calcined products of hydrotalcite-like compounds, were grown on the surface of a foam nickel by an in-situ growth method using a foam nickel substrate as the nickel source. The prepared NiAl-MMO films electrodes materials had stable electrochemical capability, remarkable electrochemical capacitor, and gave a highest specific capacitance of 667 F x g( 1). The desalination performance of material indicated high voltage and weakly alkaline solution were favored for desalination. A highest desalination efficiency was up to 58.17% when the initial concentration of Cl- was 0.003 mol x L(-1), the voltage value was 1.0 V and pH value was 8. The adsorption saturated electrodes could be rapidly regenerated with a desorption rate of 87.96% by electrodes reversion. This study provides a new choice for desalination in wastewater treatment. PMID- 27363151 TI - [Competitive Microbial Oxidation and Reduction of Arsenic]. AB - Filters are widely applied in drinking water treatment plants. Our previous study, which explored the asenic redox in a filter of drinking water plant treating underground water, found that As3+ could be oxidized to As5+ by biogenic manganese oxides, while As5+ could be reduced to As3+ by some microbial arsenic reductases in the biofilter system. This microbial competition could influence the system stability and treatment efficiency. To explore its mechanism, this study selected a manganese-oxidizing bacterial strain (Pseudomonas sp. QJX-1) and a arsenic-reducing strain (Brevibacterium sp. LSJ-9) to investigate their competitive relationship in nutrient acquisition and arsenic redox in the presence of Mn2+, As3+ or As5+ The results revealed that the concentration and valence of Mn and As varied with different reaction time; biological manganese oxides dominated the arsenic redox by rapidly oxidizing the As3+ in the existing system and the As3+ generated by arsenic reductase into As. PCR and RT-PCR results indicated that the arsenic reductase (arsC) was inhibited by the manganese oxidase (cumA). The expression of 16S rRNA in QJX-1 was two orders of magnitude higher than that in LSJ-9, which implied QJX-1 was dominant in the bacterial growth. Our data revealed that hydraulic retention time was critical to the valence of arsenic in the effluent of filter in drinking water treatment plant. PMID- 27363152 TI - [Community Characteristics of ANAMMOX Bacteria in Subsurface Flow Constructed Wetland (SSFCW) for Processing of Aquaculture Waster Water]. AB - Anaerobic ammonium oxidation (ANAMMOX) is one of the important functions in waste water treatment by subsurface flow constructed wetland (SSFCW), however, there are few studies on ANAMMOX in SSFCW environment at present. The community characteristics of ANAMMOX in the SSFCW of processing aquaculture waste water were explored in this study. In order to analyze the structure, diversity and abundance of ANAMMOX bacteria, several 16S rRNA clone libraries were constructed and real-time PCR targeting specific 16S rRNA genes together with diversity analysis was adopted. The obtained results showed that the SSFCW identified a total of three unknown clusters and two known clusters including Candidatus brocadia and Candidatus kuenenia. The dominant cluster was Candidatus brocadia. The highest diversity levels of ANAMMOX bacteria occurred in autumn (H', 1.21), while the lowest in spring (H', 0.64). The abundance of ANAMMOX bacteria in SSFCW environment ranged from 8.0 x 10(4) to 9.4 x 10(6) copies x g(-1) of fresh weight and the copy number of total bacterial 16S rRNA genes ranged from 7.3 x 10(9) to 9.1 x 10(10) copies x g(-1) of fresh weight during culture cycle. There were significant differences in the ANAMMOX bacteria abundances of different stratum and seasons in SSFCW environment, but the differences in total bacterial abundances were not obvious. In addition, the differences in ANAMMOX bacteria abundances in different stratum and seasons in SSFCW environment were irregular in different culture cycle. According to the distribution characteristics of ANAMMOX bacteria in the wetland, the denitrification effect of SSFCW could be improved by changing the supplying manners of aquaculture wastewater and adjusting the structure of wetland. The research results will provide reference for further optimizing the SSFCW and improving the efficiency of purification. PMID- 27363153 TI - [Analysis of Pathogenic Bacteria in Reclaimed Water and Impact of UV Disinfection on the Removal of Pathogenic Bacteria]. AB - In the study, 454-pyrosequencing technology was employed to investigate the species of pathogenic bacteria and the proportion of each pathogen in secondary effluent. Culture-based, qPCR and Q-RT-PCR methods were employed to analyze the removal of indicator (E. coli) and pathogen (Salmonella and Mycobacterium) by ultraviolet (UV) disinfection at a dose of 60 mJ x Cm(-2). The results showed that 11 kinds of pathogenic bacteria were found and the most abundant potentially pathogenic bacteria in the secondary effluent were affiliated with the genera of Clostridium (2.96%), Arcobacter (0.82%) and Mycobacterium (0.36%). 99.9% of culturable E. coli and Salmonella were removed by UV disinfection (60 mJ x cm( 2), however, less than 90% of culturable Mycobacterium were removed. The removal efficiencies of viable E. coli, Salmonella and Mycobacterium were low. Q-RT-PCR seemed to be a promising method for evaluating viable microorganisms in samples. Besides, pathogenic bacteria entered into VBNC state at a UV dose of 60 mJ x cm( 2). Other advanced treatment processes were needed to ensure safe utilization of reclaimed water. PMID- 27363154 TI - [Analysis of the Microbial Community Structure in Continuous Flow Reactor Enhanced by Heterotrophic Nitrification and Aerobic Denitrification Bacterium Burkholderia sp. YX02]. AB - To reveal the dynamic succession of microbial community structure along with time in bio-denitrification reactor, a continuous flow reactor containing immobilized heterotrophic nitrification-aerobic denitrification bacterium Burkholderia sp. YX02 was taken as a model. The microbial community structure in the bioreactor was analyzed by PCR-DCGE, and its correlations with environmental factors such as pH, NH4+ -N, NO2- -N, NO3- -N and COD were simultaneously investigated. The results showed that the microbial community was relatively rich during the early stage of 18 days. The similarity of community structure in different stages was not orderly declining with the operation. In addition, the structural similarity in adjacent stages firstly increased, then decreased, and eventually tended to be stable. Shannon-Wiener index firstly descended significantly, and then ascended with new microbial community emerging at the later stage. UPGMA clustering analysis roughly divided the process into three periods with certain relationship. Principal component analysis showed that during the operation of the bioreactor predominant bacterial community formed steadily and new microbial community dominated by Burkholderia sp. YX02 emerged at the later stage of the operation. Canonical correspondence analysis certificated that the structure of microbial community was most obviously affected by NO2- -N, followed by NO3- -N, NH4+ -N and COD, and pH had the least effect. PMID- 27363155 TI - [Comparative Metagenomics of BIOLAK and A2O Activated Sludge Based on Next generation Sequencing Technology]. AB - This is the first report of comparative metagenomic analyses of BIOLAK sludge and anaerobic/anoxic/oxic (A2O) sludge. In the BIOLAK and A2O sludge metagenomes, 47 and 51 phyla were identified respectively, more than the numbers of phyla identified in Australia EBPR (enhanced biological phosphorus removal), USA EBPR and Bibby sludge. All phyla found in the BIOLAK sludge were detected in the A2O sludge, but four phyla were exclusively found in the A20 sludge. The proportion of the phylum Ignavibacteriae in the A2O sludge was 2.0440%, which was 3.2 times as much as that in the BIOLAK sludge (0.6376%). Meanwhile, the proportion of the bacterial phylum Gemmatimonadetes in the BIOLAK sludge was 2.4673%, which was >17 times as much as that in the A2O sludge (0.1404%). The proportion of the bacterial phylum Chlamydiae in the BIOLAK metagenome (0.2192%) was >6 times higher than that in the A2O (0.0360%). Furthermore, 167 genera found in the A20 sludge were not detected in the BIOLAK sludge. And 50 genera found in the BIOLAK sludge were not detected in the A20 sludge. From the analyses of both the phylum and genus levels, there were huge differences between the two biological communities of A2O and BIOLAK sludge. However, the proportions of each group of functional genes associated with metabolism of nitrogen, phosphor, sulfur and aromatic compounds in BIOLAK were very similar to those in A2O sludge. Moreover, the rankings of all six KEGG (Kyoto Encyclopedia for Genes and Genomes) categories were identical in the two sludges. In addition, the analyses of functional classification and pathway related nitrogen metabolism showed that the abundant enzymes had identical ranking in the BIOLAK and A2O metagenomes. Therefore, comparative metagenomics of BIOLAK and A2O activated sludge indicated similar function assignments from the two different biological communities. PMID- 27363156 TI - [Identification and Nitrogen Removal Characteristics of a Heterotrophic Nitrification-Aerobic Denitrification Strain Isolated from Marine Environment]. AB - A heterotrophic nitrification-aerobic denitrification strain named y5 was isolated from marine environment by traditional microbial isolation method using seawater as medium. It was identified as Klebsiella sp. based on the morphological, physiological and 16S rRNA sequence analysis. The experiment results showed that the optimal carbon resource was sodium citrate; the optimal pH was 7.0; and the optimal C/N was 17. The strain could use NH4Cl, NaNO2 and KNO3 as sole nitrogen source, and the removal efficiencies were77.07%, 64.14% and 100% after 36 hours, respectively. The removal efficiency reached 100% after 36 hours in the coexistence of NH4Cl, NaNO2 and KNO3. The results showed that the strain y5 had independent and efficient heterotrophic nitrification and aerobic denitrification activities in high salt wastewater. PMID- 27363157 TI - [Removal of AOX and Chroma in Biologically Treated Effluent of Chemical Dyestuff Wastewater with Nanoscale Ni/Fe]. AB - Nanoscale Ni/Fe was applied to biologically treated effluent of chemical dyestuff wastewater. The removal rates of absorbable organic halogens (AOX) and chroma were investigated at different Ni loadings (0-5%), initial wastewater pH (4.1 10.0), Ni/Fe dosage (1-5 g x L(-1)) and reaction time (0.5-96 h). The results showed that the removal rates of AOX and chroma firstly increased and then decreased with the increase of the Ni loading, while continuously increased with the decrease of the initial wastewater pH and the increase of Ni/Fe dosage. The optimal condition was Ni loading of 1%, initial wastewater pH of 4.1 and Ni/Fe dosage of 3 g x L(-1), under which 29.2% of AOX and 79.6% of chroma were removed after 24 h reaction, and 50.6% of AOX and 80.7% of chroma were removed after 96 h reaction. GC-MS analysis revealed that toxicants such as chlorinated anilines, p nitroaniline, 4-methoxy-2-nitroaniline and halogenated hydrocarbons were efficiently removed. PMID- 27363158 TI - [Feasibility of 3BER-S Process for the Deep Denitrification in Synch with the Removal of PAEs from Reclaimed Water]. AB - In order to investigate the feasibility of deep denitrification and simultaneous removing phthalate esters (PAEs) in the process of reclaimed water treatment uses three-dimensional biofilm-electrode reactor coupled with sulfur autotrophic deep denitrification technology (3BER-S), the technological characteristics and mechanisms were analyzed based on determining the static adsorption capacity of biofilm cultured active carbon fillers in 3BER-S reactor together with the operation results of dynamic denitrification and simultaneous PAEs removing. The results showed that the average adsorption rates of DBP, DEHP were 85.84% and 97.12% in the biofilm cultured active carbon fillers, the equilibrium adsorption capacities were 0.1426 mg x g(-1) and 0.162 mg(-1) and the time spans of reaching adsorption saturation were 120 min and 60 min, respectively; The existence of PAEs had no obvious effect on denitrification, the reactor effluent concentration of TN was in range of 1-2 mg x L(-1) before and after the addition of PAEs, and the average removal rate of TN reached above 94%; 3BER-S denitrification system showed significant ability in removing PAEs, leading to effluent concentrations of DBP and DEHP of no more than 6 microg x L(-1) with removal rates of above 96%; this was due to the synergistic effect of absorption, biodegradation and electrochemistry. After treatment with 3BER-S technology, DBP and DEHP in simulative municipal secondary effluent met the regulated limitation of The Reuse of Urban Recycling Water Quality Standard for Groundwater Recharge (GB/T 19772 2005). PMID- 27363159 TI - [Influence of Reaction Time on Titanate Nanomaterials and Its Adsorptioi Capability for Lead in Aqueous Solutions]. AB - Titanate nanomaterials (TNs) were synthesized via a simple hydrothermal method using TiO2 (ST-01) and NaOH as the raw materials, and presented different morphologies by adjusting the reaction time. The physico-chemical properties of the as-prepared TNs, such as morphology, structure, surface area, and chemical composition were characterized by XRD, SEM and BET. The adsorption capability and rules of Pb(II) in aqueous solutions were tested in the static system. The results showed that the TNs prepared with 12-72 h reaction time were pure monoclinic phase titanate and their specific surface areas were in the range from 243.05 m2 x g(-1) to 286.20 m2 x g(-1). TNs with reaction time between 12-36 h mainly showed sheet structure, and those with reaction time higher than 48 h showed linear structure. The adsorption capacity of Pb(II) by TNs-12, TNs-24, TNs 36, TNs-48, TNs-60 and TNs-72 was 479.40, 504.12, 482.00, 388.10, 364.60 and 399.00 mg x g(-1), respectively. The sheet TNs had a better adsorption capacity than the linear TNs. TNs-24 had the highest adsorbing capacity. The adsorption kinetics of Pb(II) by TNs-24 followed the pseudo-second-order model, and the equilibrium data was best fitted with the Langmuir isotherm model. The equilibrium adsorption time of TNs-24 was 120 min, and the adsorption was an exothermic process, with a high adsorption capacity at low temperature or room temperature; the optimal adsorption pH was 5.0. When pH was 1.0, the desorption rate of TNs-24 could reach 99.00%, and the removal efficiency of Pb(II) by regenerated TNs was still more than 97% after six times of usage. Therefore, TNs could efficiently remove Pb(II) in aqueous solutions, and the optimal reaction time should be controlled to 12-24 h. When Cd(II) or Ni(II) existed in the solution, the equilibrium adsorption capacity and removal rate of TNs-24 were decreased. The adsorption mechanism was mainly ion-exchanged between Pb(II) and H+/Na+ in TNs. PMID- 27363160 TI - [Sorption Characteristics of Phenanthrene and 1, 1-Dichloroethene onto Reed Straw Biochar in Aquatic Solutions]. AB - The purpose of this study was to investigate the sorption characteristics of phenanthrene (PHE) and 1, 1-dichloroethene (1, 1-DCE) onto reed straw biochar at 500 degrees C in aquatic solutions. The sorption mechanisms and effects of solution pH and biochar mass on sorption intensity were discussed. The results showed that the time required to reach sorption equilibrium was 60 min and 480 min for PHE and 1, 1-DCE, respectively, with maximum removal rates of 81, 87% and 90.18%. The sorption kinetics of both PHE and 1, 1-DCE fitted the pseudo-second order model well, but the pseudo-second-order reaction rate of PHE was higher than that of 1, 1-DCE. Furthermore, the sorption processes were controlled by both membrane diffusion and intra-particle diffusion, and the latter was found to be the rate-controlling step. Sorption isotherms of the two organic pollutants fitted well with the Freundlich equation, and the sorption affinity of 1, 1-DCE onto biochar was greater than that of PHE. The total sorption mechanism of biochar was the combination of partition and adsorption, and dominated by adsorption. The adsorption capacity of 1, 1-DCE was greater than that of PHE, but its partition capacity was much smaller, indicating that pollutants' molecular volume and relative polarity would mainly affect the total sorption. Analysis of Fourier transform infrared spectroscopy (FTIR) demonstrated that oxygen- and hydrogen-containing functional groups and pi--pi interaction were important for PHE and 1, 1-DCE sorption onto biochar. The solution pH value had no significant effect on the sorption intensity of PHE and 1, 1-DCE, however, with biochar mass increasing from 5 mg to 50 mg, the equilibrium sorption amount of PHE and 1, 1 DCE decreased by 6.78 times and 2.18 times, and the removal rate increased by 20.21% and 15.78%, respectively. PMID- 27363161 TI - [Adsorption Characteristics of Norfloxacin by Biochars Derived from Reed Straw and Municipal Sludge]. AB - Two types of biochars were prepared by pyrolyzing reed straw and municipal sludge at the temperature of 500 degrees C. The structure and properties of biochars were characterized by BET, scanning electron microscope (SEM), energy dispersive spectroscopy (EDS) and fourier transform infrared spectroscopy ( FTIR ). The effects of pH value, adsorption time, temperature and initial concentration of norfloxacin (NOR) on the adsorption behaviors were determined by single factor experiments, which were used to preliminarily discuss adsorption mechanism. The results showed that the adsorption of NOR onto biochars derived from reed straw and municipal sludge could reach 70% and 60% of the total adsorption within 12 h, respectively; the maximum adsorption capacities of the two biochars were 2.13 mg x g(-1) (biochar derived from reed straw) and 2.09 mg x g(-1) (biochar derived from municipal sludge). The quantities of both absorptions increased with the decreasing solution pH. The two adsorption kinetics of NOR onto biochars followed the pseudo second order kinetic equations, and adsorption isotherms fitted well with the Langmuir equations. Adsorption thermodynamics parameters such as Gibbs free energy (AG), enthalpy (AH) and entropy (AS) indicated that the two adsorptions were endothermic reactions. Infrared spectroscopy analysis indicated that oxygen-containing functional groups on biochars provided NOR molecules with adsorptive sites, which facilitated the formation of hydrogen bonds between NOR and the biochars. PMID- 27363162 TI - [Effect of Seasonal Temperature Increasing on Nitrogen Mineralization in Soil of the Water Level Fluctuating Zone of Three Gorge Tributary During the Dry Period]. AB - To reveal the effect of seasonal temperature increasing on nitrogen mineralization in soil of the water level fluctuating soil zone of three gorge reservoir areas in the Yangtze river tributary during the dry period, surface soils were collected from the water level fluctuating zone of Pengxi river crossing two hydrological sections, i.e., upstream and downstream and three water level altitudes, 155 m (low), 165 m (middle) and 175 m (high). We incubated the soil at 25 degrees C and 35 degrees C to determine the transformation rates of nitrogen in soil of Pengxi river basin during the dry period. The result showed that TN and NO3- -N contents in the soil of upstream section and higher (175 m) altitude of water level were higher than those in downstream and low (165 m) altitude of water level, whereas the pattern for NH4+ -N was different, with higher NH4+ -N contents in downstream and low water level. The inorganic nitrogen was dominated by NO3- -N, which accounted for up to 57.4%-84.7% of inorganic nitrogen. Generally, soil ammoniation, nitration and net N mineralization increased with the rising water level altitude and stream sections (P < 0.05). In summary, nitration and net N mineralization significantly increased with increasing temperature, (P < 0.05), while ammoniation showed no difference (P > 0.05). PMID- 27363163 TI - [Effects of Warming and Straw Application on Soil Respiration and Enzyme Activity in a Winter Wheat Cropland]. AB - In order to investigate the effects of warming and straw application on soil respiration and enzyme activity, a field experiment was performed from November 2014 to May 2015. Four treatments, which were control (CK), warming, straw application, and warming and straw application, were arranged in field. Seasonal variability in soil respiration, soil temperature and soil moisture for different treatments were measured. Urease, invertase, and catalase activities for different treatments were measured at the elongation, booting, and anthesis stages. The results showed that soil respiration in different treatments had similar seasonal variation patterns. Seasonal mean soil respiration rates for the CK, warming, straw application, and warming and straw application treatments were 1.46, 1.96, 1.92, and 2.45 micromol x (m2 x s)(-1), respectively. ANOVA indicated that both warming and straw applications significantly (P < 0.05) enhanced soil respiration compared to the control treatment. The relationship between soil respiration and soil temperature in different treatments fitted with the exponential regression function. The exponential regression functions explained 34.3%, 28.1%, 24.6%, and 32.0% variations of soil respiration for CK, warming, straw application, and warming and straw application treatments, respectively. Warming and straw applications significantly (P < 0.05) enhanced urease, invertase, and catalase activities compared to CK. The relationship between soil respiration and urease activity fitted with a linear regression function, with the P value of 0.061. The relationship between soil respiration and invertase (P = 0.013), and between soil respiration and catalase activity (P = 0.002) fitted well with linear regression functions. PMID- 27363164 TI - [Distribution of Urban Soil Heavy Metal and Pollution Evaluation in Different Functional Zones of Yinchuan City]. AB - Surface soil samples (0-20 cm) from eight different functional areas in Yinchuan city were collected. There were 10 samples respectively in each functional area. The urban soil heavy metals (Zn, Cd, Pb, Mn, Cu and Cr) pollution characteristics and sources in eight different functional areas were evaluated by mathematical statistics and geostatistical analysis method. Meanwhile, the spatial distributions of heavy metals based on the geography information system (GIS) were plotted. The average values of total Zn, Cd, Pb, Mn, Cu and Cr were 74.87, 0.15, 29.02, 553.55, 40.37 and 80.79 mg x kg(-1), respectively. The results showed that the average value of soil heavy metals was higher than the soil background value of Ningxia, which indicated accumulation of the heavy metals in urban soil. The single factor pollution index of soil heavy metals was in the sequence of Cu > Pb > Zn > Cr > Cd > Mn. The average values of total Zn, Cd, Pb and Cr were higher in north east, south west and central city, while the average values of Mn and Cu were higher in north east and central city. There was moderate pollution in road and industrial area of Yinchuan, while the other functional areas showed slight pollution according to Nemoro synthesis index. The pollution degree of different functional areas was as follows: road > industrial area > business district > medical treatment area > residential area > public park > development zone > science and education area. The results indicated that the soil heavy metal pollution condition in Yinchuan City has been affected by human activities with the development of economy. PMID- 27363165 TI - [Differential Effect and Mechanism of in situ Immobilization of Cadmium Contamination in Soil Using Diatomite Produced from Different Areas]. AB - In order to understand the difference of in situ immobilization effect and mechanism of Cd contamination in soil using diatomite produced from different areas, the test was conducted using diatomite produced from Yunnan Tengchong, Jilin Linjiang, Zhejiang Shengzhou and Henan Xinyang of China as modifiers to immobilize cadmium contamination in simulated soil. The results indicated that the diatomite from all the four producing areas could effectively immobilize available Cd in soil, decreasing the available Cd content in soil by 27.7%, 28.5%, 30.1% and 57.2%, respectively when the adding concentration was 30 g x kg( 1). Their ability for immobilizing available Cd in soil followed the sequence of Henan Xinyang > Zhejiang Shengzhou > Jilin Linjiang > Yunnan Tengchong. It was also found that the physical and chemical properties of diatomite played a main role in soil cadmium immobilization, lower bulk density, larger specific surface area, more micro pores and wider distribution range of aperture were more favorable for available Cd immobilization. The results also showed that, the diatomite could control Cd contamination by changing soil physical and chemical properties, among these properties, pH and organic matter content were the key factors, increasing soil pH value and organic matter content was favorable for available cadmium immobilization, while the soil water content had little effect on available cadmium immobilization. The control of soil cadmium contamination by using diatomite to change cation exchange capacity was limited by time in some degree. The diatomite produced from Henan Xinyang, Zhejiang Shengzhou and Yunnan Tengchong increased the soil pH value and organic matter content, and was favorable for available Cd immobilization, while the diatomite from Jilin Linjiang showed converse effect. PMID- 27363166 TI - [Characteristics of Adsorption Leaching and Influencing Factors of Dimethyl Phthalate in Purple Soil]. AB - The typical soil-purple soil in Three Gorges Reservoir was the tested soil, the characteristics of adsorption leaching of dimethyl phthalate (DMP) in contaminated water by the soil, and the influencing factors in the process were conducted using soil column leaching experiment. The results showed that the parabolic equation was the best equation describing adsorption kinetics of DMP by soils. The concentration of DMP in the leaching solution had significant effect on the adsorption amounts of DMP. With the increasing concentration of DMP in the leaching solution, the adsorption capacities of DMP by purple soil increased linearly. The ionic strength and pH in leaching solution had significant effects on adsorption of DMP. On the whole, increasing of the ionic strength restrained the adsorption. The adsorption amounts at pH 5.0-7.0 were more than those under other pH condition. The addition of exogenous organic matter (OM) in purple soil increased the adsorption amount of DMP by purple soil. However, the adsorption amount was less than those with other addition amounts of exogenous OM when the addition of exogenous OM was too high (> or = 30 g x kg(-1)). The addition of surfactant sodium dodecylbenzene sulfonic acid (SDBS) in purple soil increased the adsorption amount of DMP by purple soil. The adsorption amount was maximal when the addition amount of SDBS was 50 mg x kg(-1). However, the adsorption amounts decreased with increasing addition amounts of SDBS although the adsorption amounts were still more than that of the control group, and the adsorption amount was almost equal to that of the control group when the addition amount of SDBS was 800 mg x kg(-1). Continuous leaching time affected the vertical distribution of DMP in the soil column. When the leaching time was shorter, the upper soil column adsorbed more DMP, while the DMP concentrations in upper and lower soil columns became similar with the extension of leaching time. PMID- 27363167 TI - [Cd Runoff Load and Soil Profile Movement After Implementation of Some Typical Contaminated Agricultural Soil Remediation Strategies]. AB - Owing to the strong ability to immobilize and hyperaccumulate some toxic heavy metals in contaminated soils, the biochar, lime and such as hyperaccumulator ramie received increasing interests from crops and environment safety in recent years. Outdoor pot experiment was conducted to compare the impacts of lime and biochar addition in paddy rice treatment, hyperaccumulator ramie and ramie combined with EDTA of plant Phytoremediation methods on soil available Cd dynamics in rainfall runoff and the mobility along soil profile, under both natural acid precipitation and acid soil conditions. The results showed that, biochar addition at a 2% mass ratio application amount significantly increased soil pH, while ramie with EDTA application obviously decreased soil pH compared to ramie monoculture. Within the same rainfall events, water soluble Cd concentration in surface runoff of ramie treatments was significantly higher than those of waterlogged rice treatments, and Cd concentration in runoff was obviously increased after EDTA addition, whereas lime at a 0.3% mass ratio application amount as additive had no obvious impact on soil pH and Cd speciation change, which may be due to the low application amount. During the whole experimental period , water soluble Cd concentration of rainfall runoff in spring was higher than that in summer, showing the same seasonal characteristics in all treatments. Biochar addition could significantly decrease available Cd content in 0-20 cm soil layer and with certain preferable persistency effects, whereas EDTA addition treatment obviously increased available Cd of 0-20 cm soil layer compared to other treatments, and obvious Cd element activation phenomenon in 20 40 cm soil layer was observed after EDTA addition. In conclusion, lime and biochar as environmental and friendly alkaline Cd immobilization materials showed lower environment risk to surface and ground receiving water, but attention should be paid to phytoremediation enhanced with EDTA or other organic acid before promotion and field application for heavy metals removal from contaminated soils. PMID- 27363168 TI - [Concentrations and Component Profiles PAHs in Surface Soils and Wheat Grains from the Cornfields Close to the Steel Smelting Industry in Handan, Hebei Province]. AB - In this study, paired surface soil and mature wheat grain samples were collected in the cornfields near the large Handan Steel Manufacturer; and the total concentrations and compositional profiles of the parent PAHs were measured, then the spatial distribution characteristics and correlation with total organic carbon fractions in soil were determined. Accordingly, a preliminary source identification was performed, and the association between PAHs in surface soil and wheat grain was briefly discussed. The median concentration of total PAHs in surface soils from the cornfields of Handan was 398.9 ng x g(-1) (ranged from 123.4 ng x g(-1) to 1626.4 ng x g(-1), where around 18% and 10% of all the studied soil samples were over the corresponding quality criteria for total PAHs and B [a] P in soils, respectively. The MMW and HMW species were the main components in the compositional profiles of surface soils. Based on the specific isomeric ratios of PAHs species, coal/biomass combustion and transportation fuel (tail gas) were the dominant mixed sources for the local PAHs emission. The fractions of surface soil TOC had significant positive correlations with the total PAHs and also with the individual components with different rings. In addition, the median concentration of total PAHs in wheat grains collected in the cornfields near the Handan Steel Manufacture was 27.0 ng x g(-1) (ranged from 19.0-34.0 ng x g(-1)). The levels in wheat grains were not high, and lower than the related hygienic standards of food proposed by EU and China. The LMW and MMW PAHs with 2 to 4 rings occupied a larger proportion, more than 84% of the total PAHs, which was largely different from the component profiles in surface soils. This situation suggested that the local sources of PAHs in wheat grains may originate not only from surface soil via root absorption and internal transportation, but also from ambient air through dry and wet deposition on the leaf surface (stoma). PMID- 27363169 TI - [Effect of Arbuscular Mycorrhiza (AM) on Tolerance of Cattail to Cd Stress in Aquatic Environment]. AB - Hygrophytes are planted more and more in landscaping and greening in many cities, but they often encounter threat from environmental pollution. Arbuscular mycorrhiza ( AM ) have been confirmed to enhance the tolerance of terrestrial plants to environmental pollution in many previous studies, but it is unclear how they affect hygrophytes. In the present study, a hydroponic culture experiment was carried out to investigate the effects of AM fungi (Glomus etunicatum) inoculation on the tolerance of cattail (Typha latifolia) to different concentrations Cd2+ (0, 2.5, 5.0 mg x L(-1)). The aim was to provide reference for evaluating whether mycorrhizal technology can be used to enhance the tolerance of hygrophytes to environmental pollution. The results showed that symbiotic association was well established between AM fungi and cattail roots, and the mycorrhizal colonization rates (MCR) were beyond 30%. However, MCR presented downward trend one month after mycorrhizal cattails were transported to solution, and the maximal decrease was 25.5% (P < 0.05). AM increased pigment concentrations and peroxidase (POD) activity in cattail leaves, and also increased roots radial oxygen loss. However, AM only produced significant effect on increase of fresh weight in 5 mg x L(-1) Cd2+ solution. Although plant growth was inhibited by 5 mg x L(-1) Cd2+ and MCR was lower, AM increased Cd uptake of cattail at the two Cd2+ levels, and the maximal increments were 40.24% and 56.52% in aboveground and underground parts, respectively. This study indicates that AM has potential to enhance the tolerance of hygrophytes to environmental pollution and might be used to remedy heavy metal pollution. PMID- 27363170 TI - [Acute Toxic Effects of Bromate on Aquatic Organisms]. AB - Acute toxic effects of potassium bromate, sodium bromate and potassium bromide on luminescent bacteria, water flea, green alga and zebrafish were studied using standard toxic testing methods. The results showed that the pollutants had no effect on the luminous intensity of luminescent bacteria. The 96 h EC5. of potassium bromate on Scenedesmus obliquus was 738.18 mg x L(-1), 48 h EC50 on Daphnia magna and Moina was 154.01 mg x L(-1) was 161.80 mg x L(-1), while 48 h LC50 was 198 52 mg x L(-1), 175.68 mg x L(-1), and 96 h LC50 on zebrafish was 931.4 mg x L(-1). The 96 h EC50 of sodium bromate on Scenedesmus obliquus was 540.26 mg x L(-1), 48 h EC50 Daphnia magna and Moina was 127.90 mg x L(-1), 111.07 mg x L(-1), while 48 h LC50 was 161.80 mg x L(-1), 123.47 mg x L(-1), and 96 h LC50 on zebrafish was 1065.6 mg x L(-1). But the effects of potassium bromide on the above several kinds of aquatic organisms were far smaller than those of potassium bromate and sodium bromate. The toxic effects on test organisms were due to the impacts of bromate after the comparison of different pollutants, and the effects were more obvious with the increase of exposure time. The order of sensitivity to the toxic effects of bromate was Daphnia magna, Moina > Scenedesmus obliquus > zebrafish > Chlorella vulgaris, luminescent bacteria. PMID- 27363171 TI - [Development of Self-assembled Dumbbell-like Fe3O4 Micro/nanomaterial for Application in Thermocatalytic Degradation of Polybrominated Biphenyls]. AB - Polybrominated biphenyls (PBBs) are a group of new persistent organic pollutants, which have high toxicity and long-term bioaccumulation, and cause potential risks to human beings and aquatic ecosystem. Self-assembled dumbbell-like Fe3O4 was synthesized via ethylene-glycol mediated method to degrade PBBs, using BB209 as a model compound. The results showed that the growth process of dumbbell-like Fe3O4 precursor had two stages involving a fast nucleation of amorphous primary particles followed by a slow aggregation and crystallization of primary particles. Dumbbell-like Fe3O4 showed high activity for degradation of BB209 at the reaction time of 30 min with the degradation efficiency of nearly 100% at 300 degrees C. A whole series of nonabromobiphenyl to monobromobiphenyl and biphenyls were detected as the degradation products of BB209 by dumbbell-like Fe3O4, indicating the occurrence of successive hydrodebromination reaction. Furthermore, the amounts of three NoBB isomers followed the order of BB207 > BB208 > BB206, indicating that the reactivity of C--Br of BB209 was in order of meta- > para- > ortho-positions. PMID- 27363172 TI - [Impact of Salinity on Leachate Treatment and N2O Releases from Semi-aerobic Aged refuse Bioreactor]. AB - Semi-aerobic Aged-refuse Bioreactor (SAARB) has a good effect on nitrogen removal in leachate, but a strong greenhouse gas (N2O) was generated during the nitrification and denitrification process. The effect of salinity (7-30 g x L( 1)) on the leachate treatment and the N2O production from SAARB system was investigated. Experimental results showed that salinity ranging from 7 to 30 g x L(-1) had no significant effect on COD removal, and the removal efficiency was always more than 85%. On the contrary, it had a strong influence on the removal of nitrogen. The removal efficiencies of NH4+ -N and TN decreased from 98. 23% and 91.48% at 7 g x L(-1) salt to 31.75% and 34.24% at 30 g x L(-1) salt, respectively. Moreover, there was significant nitrite (NO2- -N) accumulation in the presence of 30 g x L(-1) salt. Meanwhile, salinity had different inhibition strength on nitrification and denitrification bacteria, and the order of inhibition strength was as follows: nitrification bacteria > denitrification bacteria. In addition, the N2O production increased with salinity concentration, and the highest N2O accumulation (1397 microg +/- 369.88 microg) was observed with addition of 30 g x L(-1) salt, which accounted for 8.87%o of the total nitrogen removal. Meanwhile, it was 6-117 times higher in the presence of 30 g x L(-1) salt than that in low salinity conditions (7-20 g x L(-1)). And the peak time of the N2O production showed a delayed trend. These results indicated that salinity recirculation in leachate had a negative effect on the nitrogen removal and N2O production. Overall, salinity seemed to be a key parameter during leachate recirculation. PMID- 27363173 TI - [Evaluating the Significance of Odor Gas Released During the Directly Drying Process of Sludge: Based on the Multi-index Integrated Assessment Method]. AB - Co-processing of sewage sludge using the cement kiln can realize sludge harmless treatment, quantity reduction, stabilization and reutilization. The moisture content should be reduced to below 30% to meet the requirement of combustion. Thermal drying is an effective way for sludge desiccation. Odors and volatile organic compounds are generated and released during the sludge drying process, which could lead to odor pollution. The main odor pollutants were selected by the multi-index integrated assessment method. The concentration, olfactory threshold, threshold limit value, smell security level and saturated vapor pressure were considered as indexes based on the related regulations in China and foreign countries. Taking the pollution potential as the evaluation target, and the risk index and odor emission intensity as evaluation indexes, the odor pollution potential rated evaluation model of the pollutants was built according to the Weber-Fechner law. The aim of the present study is to form the rating evaluation method of odor potential pollution capacity suitable for the directly drying process of sludge. PMID- 27363174 TI - Respecting the human element in HR. PMID- 27363175 TI - Redesigning labor management for enhanced quality of care. PMID- 27363176 TI - Improve staff relationships. PMID- 27363177 TI - Investing in the right staff yields better patient experience. PMID- 27363178 TI - APPLYING POSITIVE PSYCHOLOGY TO THE PRACTICE OF MEDICINE. PMID- 27363179 TI - 'The Happiness Advantage' might boost productivity rates by 31%. PMID- 27363180 TI - Strength in numbers: MGMA member turns the tide in payer-provider struggle. PMID- 27363181 TI - Reading between the lines. PMID- 27363183 TI - Mind over matter: Mindfulness boosts productivity. PMID- 27363182 TI - Shaping tomorrow's healthcare leaders. PMID- 27363184 TI - Star power. PMID- 27363185 TI - Tapping your power: New volunteer structure capitalizes on member voice. PMID- 27363186 TI - Service line co-management agreements enhance patient outcomes, generate income. PMID- 27363187 TI - BEST OF THE BEST MGMA AWARD RECIPIENTS' INNOVATIONS AND INVOLVEMENT IMPROVE HEALTHCARE INDUSTRY. PMID- 27363188 TI - Benchmarking 301: Advanced practice metrics provide actionable insight. PMID- 27363189 TI - Staffing changes enhance patient access. PMID- 27363190 TI - Are you losing the high-deductible game? ACMPE Fellow's research IDs issue for colleagues. PMID- 27363191 TI - 5 steps to accelerating cash flow. PMID- 27363192 TI - Comparing PCMH accreditations: MGMA report helps members ID best program. PMID- 27363193 TI - Physician retreat reveals the value of strong administrative leadership. PMID- 27363195 TI - [Predicting genetic modification targets based on metabolic network analysis--a review]. AB - Construction of artificial cell factory to produce specific compounds of interest needs wild strain to be genetically engineered. In recent years, with the reconstruction of many genome-scale metabolic networks, a number of methods have been proposed based on metabolic network analysis for predicting genetic modification targets that lead to overproduction of compounds of interest. These approaches use constraints of stoichiometry and reaction reversibility in genome scale models of metabolism and adopt different mathematical algorithms to predict modification targets, and thus can discover new targets that are difficult to find through traditional intuitive methods. In this review, we introduce the principle, merit, demerit and application of various strain optimization methods in detail. The main problems in existing methods and perspectives on this emerging research field are also discussed, aiming to provide guidance to choose the appropriate methods according to different types of products and the reliability of the predicted results. PMID- 27363196 TI - [Progress in ubiquitin, ubiquitin chain and protein ubiquitination]. AB - Protein ubiquitination is one of the most important and widely exist protein post translational modifications in eukaryotic cells, which takes the ubiquitin and ubiquitin chains as signal molecules to covalently modify other protein substrates. It plays an important roles in the control of almost all of the life processes, including gene transcription and translation, signal transduction and cell-cycle progression, besides classical 26S protesome degradation pathway. Varied modification sites in the same substrates as well as different types of ubiquitin linkages in the same modification sites contain different structural information, which conduct different signal or even determine the fate of the protein substrates in the cell. Any abnormalities in ubiquitin chain formation or its modification process may cause severe problem in maintaining the balance of intracellular environment and finally result in serious health problem of human being. In this review, we discussed the discovery, genetic characteristics and the crystal structure of the ubiquitin. We also emphasized the recent progresses of the assembly processes, structure and their biological function of ubiquitin chains. The relationship between the disregulation and related human diseases has also been discussed. These progress will shed light on the complexity of proteome, which may also provide tools in the new drug research and development processes. PMID- 27363197 TI - [Biosynthesis of indigo and indirubin by whole-cell catalyst designed by combination of protein engineering and metabolic engineering]. AB - The phenylacetone monooxygenase, isolated from Thermobifida fusca, mainly catalyzes Baeyer-Villiger oxidation reaction towards aromatic compounds. Met446 plays a vital role in catalytic promiscuity, based on the structure and function of phenylacetone monooxygenase. Mutation in Met446 locus can offer enzyme new catalytic feature to activate C-H bond, oxidizing indole to finally generate indigo and indirubin, but the yield was only 1.89 mg/L. In order to further improve the biosynthesis efficiency of the whole-cell catalyst, metabolic engineering was applied to change glucose metabolism pathway of Escherichia coli. Blocking glucose isomerase gene pgi led to pentose phosphate pathway instead of the glycolytic pathway to become the major metabolic pathways of glucose, which provided more cofactor NADPH needed in enzymatic oxidation of indole. Engineering the host E. coli led to synthesis of indigo and indirubin efficiency further increased to 25 mg/L. Combination of protein and metabolic engineering to design efficient whole-cell catalysts not only improves the synthesis of indigo and indirubin, but also provides a novel strategy for whole-cell catalyst development. PMID- 27363198 TI - [Optimization of 1,2,4-butanetriol synthetic pathway in Escherichia coli]. AB - 1,2,4-Butanetriol (BT) is an important non-natural chemical with a variety of industrial applications. A recombinant Escherichia coli biosynthesizing BT from D xylose was constructed by heterologously expressing xdh and mdlC, and knocking out competing pathway genes including xylA, xylB, yjhE, yagH and ycdW. To optimize BT synthesis pathway, the third catalytic step that catalyzes the decarboxylation reaction of 3-deoxy-D-glycero-pentulosonic acid was identified as a potential bottleneck. Consequently, 2-keto acid decarboxylases from three different microorganisms were screened, and the kivD gene from Lactococcus lactis was found to increase BT titer by 191%. The improved strain BW-025 reached a final BT titer of 2.38 g/L under optimized transformation conditions. Attempts on synthetic pathway optimization were also made by fine-tuning the expression levels of each enzyme involved in the whole pathway based on BW-025. As a result, an xdh overexpressed recombinant strain, BW-074 was finally generated, with 48.62% higher BT production than that of BW-025. PMID- 27363199 TI - [Identification and expression patterns of anterior silk gland specific cuticle protein Bm11721 in the silkworm (Bombyx mori)]. AB - The silk gland of silkworm is the organ of silk protein synthesis and secretion. According to the morphological and functional differences, silk gland can be divided into anterior silk gland (ASG), middle silk gland (MSG) and posterior silk gland (PSG). ASG is the place for silk proteins conformation changes although it cannot synthetize silk proteins. ASG has narrow luminal structures and rigid wall which consists of chitin and cuticle proteins so that it can provide the shearing force which plays an important role in the silk protein conformation changes. The objective of this study is to identify the new chitin binding proteins in ASG of silkworm (Bombyx mori), and to analyze their expression patterns in different tissues. We identified a cuticle protein with chitin binding domain Bml1721 (GenBank Accession No. NM-001173285.1) by chitin affinity chromatography column. We also expressed the recombinant protein as inclusion body using the prokaryotic expression system, and then successfully purified the recombinant protein by nickel affinity chromatography column to generate the polyclonal antibodies. The expression patterns analysis in various tissues showed that both in transcriptional and protein levels Bm11721 was specifically expressed in ASG. Furthermore, the expression level of Bm 11721 protein was unchanged during the 5th instar. Immunofluorescence analysis revealed that Bm1 1721 was located in the ASG inner membrane. It is proposed that Bm11721 is a component of inner membrane and probably provides the shearing force for conformational changes. PMID- 27363200 TI - [Degradation of urea and ethyl carbamate in Chinese Rice wine by recombinant acid urease]. AB - Ethyl carbamate (EC) as a potential carcinogen commonly exists in traditional fermented foods. It is important eliminate urea that is the precursors of EC in many fermented foods, including Chinese Rice wine. On the basis of achieving high level overexpression of food-grade ethanol-resistant acid urease, we studied the hydrolysis of urea and EC with the recombinant acid urease. Recombinant acid urease showed degraded urea in both the simulated system with ethanol and Chinese Rice wine (60 mg/L of urea was completely degraded within 25 h), indicating that the recombinant enzyme is suitable for the elimination of urea in Chinese Rice wine. Although recombinant acid urease also has degradation catalytic activity on EC, no obvious degradation of EC was observed. Further investigation results showed that the Km value for urea and EC of the recombinant acid urease was 0.7147 mmol/L and 41.32 mmol/L, respectively. The results provided theoretical foundation for realizing simultaneous degradation of urea and EC. PMID- 27363201 TI - [D-mannose-conjugated polymeric micelles for targeted drug delivery]. AB - Polymeric micelles have exhibited attractive properties as drug carriers, such as high stability in vivo and good biocompatibility, and been successfully used to dissolve various drugs of poor aqueous solubilities. In this study, we developed a new type of polymeric micelles with mannose-mediated targeting and pH responsive drug release properties for anticancer drug delivery. The polymeric micelles were prepared from an amphiphilic polymer, poly (glycidyl methacrylate) g-mannose (PGMA-Mannose). An anticancer drug, doxorubicin (DOX), was encapsulated into the micelles during the micellization, and could be released rapidly under acidic condition. The specificity of cellular uptake of the micelles by two different cell lines was studied using confocal laser scanning microscopy and the MTT assay. DOX-loaded micelles were efficiently trapped by mannose-receptor overexpressing cancer cells MDA-MB-231, whereas mannose- receptor-poor cells HEK293 showed much lower endocytosis towards the micelles under the same conditions. Thus, DOX-loaded micelles displayed higher cytotoxicity to MDA-MB-231 cancer cells as compared with free DOX. The present study demonstrates that PGMA Mannose micelles are a promising targeted drug delivery system for cancer therapy. PMID- 27363202 TI - [Pilot-scale purification of rF1-V fusion protein of Yersinia pestis and characterization of its immunogenicity]. AB - Recombinant Fl-V (rFl-V) fusion protein is the main ingredient of the current candidate vaccine against Yersinia pestis infection, which has been under investigation in clinical trial in USA. We investigated the soluble expression conditions of rF1-V in Escherichia coli BL21 (DE3) that we constructed before. After scale-up and optimization of fermentation processes, we got the optimized fermentation process parameters: the culture was induced at the middle exponential phase with 50 umol/L of IPTG at 25 degrees C for 5 h. Soluble rFl-V protein was isolated to 99% purity by ammonium sulfate precipitation, ion exchange chromatography, hydrophobic chromatography and gel filter chromatography. The protein recovery was above 20%. Protein identity and primary structure were verified by mass spectrometry and Edman sequencing. Results of purity, quality and western blotting analysis indicated that the target protein is a consistent and properly folded product. Furthermore, the immunogenicity of various antigens formulated with aluminum hydroxide adjuvant was evaluated in mice. Serum antibody titers of 4 groups including 20 ug rFl, rV and rFl-V and 10 ug rFl+10 ug rV, were assayed by ELISA after 2 doses. The antibody titers of anti Fl with 20 ug rFl-V were obviously higher than titers with other groups; meanwhile there were no significant difference of anti-V antibody titers among them. These findings confirm that rFl-V would be the active pharmaceutical ingredient of the plague subunit vaccine. PMID- 27363203 TI - [Preparation and detection of anti-influenza A virus polymerase basic protein 1 polyclonal antibody]. AB - Influenza A virus is an enveloped virus that belongs to the Orthomyxoviridae family. It has 8 negative RNA segments that encode 16 viral proteins. The viral polymerase consists of 3 proteins (PB 1, PB2 and PA) which plays an important role in the transcription and replication of the influenza A virus. Polymerase basic protein 1 (PB 1) is a critical member of viral polymerase complex. In order to further study the function of PB1, we need to prepare the PB1 antibody with good quality. Therefore, we amplified PB1 conserved region (nt1648-2265) by PCR and cloned it into pET-30a vector, and transformed into Escherichia coli BL2 1. The expression of His tagged PB 1 protein was induced by IPTG, and His-PB 1 proteins were purified by Ni-NTA resin. For preparation of PB 1 protein antiserum, rabbits were immunized with His-PB 1 fusion protein 3 times. Then the titer of PB 1 polyclonal antibody was measured by indirect ELISA. The antibody was purified by membrane affinity purification and subjected to immunoblotting analysis. Data showed that PB1 antibody can recognize PB 1 protein from WSN virus infected or pCMV FLAG-PB 1 transfected cells. Meanwhile, PB 1 antibody can also recognize specifically other subtype strains of influenza A virus such as H9N2 and H3N2. PB 1 polyclonal antibody we generated will be a useful tool to study the biological function of PB1. PMID- 27363204 TI - [Markerless DNA deletion based on Red recombination and in vivo I-Sec I endonuclease cleavage in Escherichia coli chromosome]. AB - Red-based recombineering has been widely used in Escherichia coli genome modification through electroporating PCR fragments into electrocompetent cells to replace target sequences. Some mutations in the PCR fragments may be brought into the homologous regions near the target. To solve this problem in markeless gene deletion we developed a novel method characterized with two-step recombination and a donor plasmid. First, generated by PCR a linear DNA cassette which comprises a I-Sec I site-containing marker gene and homologous arms was electroporated into cells for marker-substitution deletion of the target sequence. Second, after a donor plasmid carrying the I-Sec I site-containing fusion homologous arm was chemically transformed into the marker-containing cells, the fusion arms and the marker was simultaneously cleaved by I-Sec I endonuclease and the marker-free deletion was stimulated by double-strand break mediated intermolecular recombination. Eleven nonessential regions in E. coli DH1 genome were sequentially deleted by our method, resulting in a 10.59% reduced genome size. These precise deletions were also verified by PCR sequencing and genome resequencing. Though no change in the growth rate on the minimal medium, we found the genome-reduced strains have some alteration in the acid resistance and for the synthesis of lycopene. PMID- 27363205 TI - [Site-specific PEGylation of recombinant lysostaphin]. AB - Lysostaphin (Lysn) is an antibacterial metalloendopeptidase that cleaves the pentaglycin bridges in the cell wall of Staphylococci. Although many studies have demonstrated its high activity in vitro, the medical application of Lysn has been hampered by its short half-life in vivo. In order to enhance its stability in vivo without significantly suppressing the enzymatic activity, we designed and tested eight single cysteine substitutions in Lysn for covalent attachment of polyethylene glycol chains (PEGylation). The purified mutants, fully reduced by Dithiothreitol (DTT), were treated with mPEG-MAL(20 kDa). The PEG modification efficiency was above 70% as determined by reverse-phase high-pressure liquid chromatography (HPLC) analysis. The PEG-Lysn proteins were further purified by cation exchange chromatography (MacroCap SP), reaching at least 95% purity. The activities of the PEG-Lysn proteins were determined by the turbidity and minimum inhibitory concentration (MIC) assays. We found that the PEGylated V240C and T244C mutants retained about 50% of the original antibacterial activity of Lysn. Overall, this study will help develop highly stable and active PEG-Lysn to treat systemic S. aureus infections. PMID- 27363206 TI - Optimization and application of protein C-terminal labeling by carboxypeptidase Y. AB - Proteolytic cleavage is one of the post-translational modifications and plays important roles in many biological processes, such as apoptosis and tumor cell metastasis. The identification of the cleavage events can improve our understanding of their biological functions in these processes. Although proteomic approaches using N-terminal labeling have resulted in the discovery of many proteolytic cleavages, this strategy has its own inherent drawbacks. Labeling of protein C-termini is an alternative approach. Here, we optimized the labeling procedure in the profiling protein C-termini by enzymatic labeling (ProC TEL) and improved the labeling efficiency for the positive isolation of protein C terminal peptides and mass spectrometric identification. We applied this approach to a complex protein mixture from Escherichia coli and identified many C-terminal peptides and internal cleaved peptides from more than 120 proteins. From the identified cleavages, we found several previously known internal proteolytic cleavage sites and many novel ones which may play roles in regulating normal biological processes. This work provides a potential new way, complementary to the N-terminomics, for the identification of proteolytic cleavages in complex biological systems. PMID- 27363207 TI - Creativity and the Brain. PMID- 27363208 TI - Stellate ganglion blockade-techniques and modalities. AB - Stellate ganglion block (SGB) is utilized in the diagnosis and management of various vascular disorders and sympathetically mediated pain in upper extremity, head and neck. The stellate ganglion lies medial to the scalene muscles, lateral to longus coli muscle, esophagus, trachea and recurrent laryngeal nerve, anterior to C7 transverse process and prevertebral fascia, superior to the subclavian artery and posterior to vertebral vessels. Consequently, inadvertent placement of the needle tip into these soft tissues and vessels occur with blind technique. Henceforth, various interventional modalities are being used for SGB, these have been reviewed in this paper. Various techniques of SGB have been described, and vary from the use of standard blind technique to the use of fluoroscopy, computerized tomography, magnetic resonance imaging, and radio nucleotide tracers. However, these techniques may not be practical in a clinical setting, insofar as they are time consuming, costly, and may involve radiation exposure. The use of fluoroscopy does not visualize the blood vessels close to the stellate ganglion. Ultrasounds are the alternative. They help in visualization of soft tissues to prevent complications and help in deposition of drug subfascially, under direct visual control. PMID- 27363209 TI - Chemical ablation of stellate ganglion for head and neck cancer pain. AB - We present a case of patient with orofacial cancer having pain on one side of face affecting her ability to speak, chew, swallow and sleep leading to emotional and behavioral deterioration. A diagnostic stellate ganglion block was performed followed by chemical neurolysis using phenol under ultrasound guidance, to prevent complications due to inadvertent spread of drug. Her pain scores decreased drastically, she was able to chew and swallow. Weighing the risk of permanent Horner's syndrome or motor paralysis with benefit of improvement in basic functioning of debilitated patients chemical neurolysis of stellate ganglion can be performed with advanced imaging modalities. PMID- 27363210 TI - The use of ultrasound in France: a point of view from experienced regional anesthesiologists. AB - A cross-sectional survey study on French practice in ultrasound-guided regional anesthesia was carried out. A questionnaire (demographic data, assessment of the likely benefits of ultrasonography, and its use in daily practice: blocks and hygiene) was emailed to all members of the French-speaking association of anesthesiologists involved in regional anesthesia. The questionnaire was filled out and returned by 634 experienced anesthesiologists. An ultrasound machine was available in 94% of cases. Ultrasound-guided regional anesthesia has become the gold standard technique for three-quarters of responders. Axillary, interscalene, popliteal sciatic and femoral nerve blocks were performed by more than 90% of responders, most frequently under ultrasound supervision. Conversely, ultrasound guidance was rarely used for spinal or deep nerve blocks. A specific sterile sheath was used in only 43% of cases. The present study confirms that ultrasound guidance has gained in popularity for many superficial, but not deep, regional anesthesia procedures in France. PMID- 27363211 TI - Why should the anesthesiologist evaluate nutritional status? AB - BACKGROUND: The anesthesiologist's involvement in perioperative medicine has significantly changed. In order to identify patients at risks of perioperative complications, the anesthesiologist has to consider, amongst others, screening and management of undernutrition. For this purpose knowledge of prevalence and risk factors, along with screening tools and guidelines for an adapted nutritional management and outcomes of renutrition are mandatory. The present review intends to provide these tools to the Anesthesiologists. METHOD: We conduct a literature review in Pubmed, Direct Science and Cochrane Library without limit of time related to undernutrition in the perioperative period. RESULTS: Undernutrition is common in surgical patients. Undernutrition is associated with an increase of morbidity, mortality, length of hospital stay and costs. Undernutrition could probably be detected during the anesthetic consultation with simple and rapid tests, such as SNAQ, MST, MUST and NRS-2002. Nevertheless, further studies are needed to validate such tests in surgical patients. Waiting for these results, we prefer MUST. The implementation of nutritional support recommendations would reduce postoperative complications. CONCLUSION: The anesthesiologist could play an important role in undernutrition screening and its management in order to reduce perioperative morbidity. PMID- 27363212 TI - Ultrasound assessment of lung consolidation and reaeration after pleural effusion drainage in patients with Acute Respiratory Distress Syndrome: a pilot study. AB - PURPOSE: The aim of the pilot study was to assess by ultrasound changes in dimensions of lung consolidation and reaeration after drainage of large pleural effusion in patients with acute respiratory distress syndrome (ARDS). METHODS: Lung ultrasound and blood gas were performed before, 2 hours (H2) and 24 hours (H24) after drainage of pleural effusion. Lung ultrasound aeration score was calculated. Cephalocaudal dimension and diaphragmatic transversal area of lung consolidation were measured. RESULTS: Ten patients were studied. Median volume of drained effusion was 675 ml at H2 and 895 at H24. Two hours after drainage, dimension of cephalocaudal consolidation and diaphragmatic transversal area decreased significantly. Lung reaeration after drainage occurred mainly in latero inferior and postero-superior regions. PaO2/FiO2 increased significantly at H24. CONCLUSIONS: Ultrasound is a useful method to assess lung consolidation after pleural effusion drainage. Drainage of pleural effusion may lead to a decrease of lung consolidation and improvement of lung reaeration. PMID- 27363213 TI - Correlation of bupivacaine 0.5% dose and conversion from spinal anesthesia to general anesthesia in cesarean sections. AB - BACKGROUND: Failed spinal anesthesia for cesarean sections may require conversion to general anesthesia. The aim of this study was to determine whether the administered spinal bupivacaine dose for performing a cesarean section under spinal anesthesia was related to the conversion rate to general anesthesia. METHODS: Retrospective analysis was performed on 1252 electronic data and file of patients who underwent a cesarean section under spinal anesthesia between 2004 and 2011. RESULTS: In 15 patients, spinal anesthesia was converted into general anesthesia due to block failure. Patients in whom a bupivacaine dose of 8 mg or smaller was administered had significantly higher conversion rate (3/61 (4.9%) patients and 12/1191 (1.0%) patients, respectively; p < 0.05.). The relative risk of conversion with a 8 mg dose or lower is 4.88 (95% CI 1.41 - 16.85). CONCLUSION: This retrospective study shows that a low dose administration a bupivacaine 0.5% for spinal anesthesia in cesarean section patients elicits significantly more frequent conversion to general anesthesia. PMID- 27363214 TI - Recovery of brain function after cardiac arrest, case report and review. AB - Cerebral hypoxia during cardiac arrest is the leading cause of mortality and morbidity in survival victims. To reduce cerebral damage, studies focus on finding effective treatments during the resuscitation period. Our report focuses on a 36-year-old police officer who had had two cardiac arrests (one at home and one at the hospital). After acute treatment, his cardiac and brain functions recovered impressively. Neuropsychological results were normal except for mild anomia. He also reported some retrograde memory loss. Surprisingly, he also reported an improvement in a very specific capacity, his episodic memory. We here review the possible causes and mechanisms that may have affected his memory abilities. PMID- 27363215 TI - Anesthetic management in patient with neurofibromatosis: a case report and literature review. AB - OBJECTIVE: We report the anesthesia management of a 15 years-old patient with neurofibromatosis type 1, scheduled for resection of a tumor located in the occipitocervical region. In addition, we review the pertaining literature, emphasizing the anesthetic implications of neurofibromatosis manipulation. CASE : A 15-years-old female patient, with Neurofibromatosis type 1 was diagnosed with a large tumor in occipitocervical region suggestive of a plexiform neurofibroma. She presented with cervical instability, difficulty in positioning due to the large cervical mass and other predictors of airway difficulty. Awake intubation was carried out with fiberoptic bronchoscopy after anesthetic block of the airway and remifentanil infusion at low doses (0.05 mcg/kg/min). An inadvertent lesion in the left vertebral artery during the surgical procedure was well controlled by fluid replacement, red blood cell and plasma infusion and norepinephrine. The histopathological report revealed a malignant peripheral nerve sheath tumor originated from a neurofibroma in the craniocervical region. Two months after surgery the patient presented a right crural deficit due to tumor recurrence. CONCLUSION: This case report demonstrates the importance of knowing the anesthetic peculiarities of patients affected by Neurofibromatosis type 1 submitted to surgery. Neurofibromatosis is a rare pathology in surgical centers, which requires special attention from the anesthesiologist. PMID- 27363216 TI - [Diagnostic Ability of Natriuretic Peptides for Heart Failure According to eGFR Level: Comparison between Brain Natriuretic Peptide and Amino-Terminal Probrain Natriuretic Peptide]. AB - Although the influence of reduced kidney function on natriuretic peptides (B-type natriuretic peptide [BNP] and amino terminal probrain natriuretic peptide [NT]) is clear, effect of kidney function on the difference of diagnostic ability for heart failure by these peptides is not obvious. The aim of this study was to examine the relationship between natriuretic peptide concentrations and echocardiographic findings according to eGFR level of the patients. In addition, we compared diagnostic ability of BNP with that of NT according to eGFR level. The eGFR levels were classified by based on CKD stage (>= 60, 45-59, 30-44, 15 29, < 15 and on maintenance HD). Patients who underwent the measurements of BNP, NT and serum creatinine concentrations, as well as echocardiography between March and October in 2011 were enrolled (n = 1,297). The left ventricular mass index was greater in patients with eGFR < 60 than in those with eGFR >= 60, but EF (%) was not different among eGFR level (except eGFR30-44). The percentage of patients with heart failure in those with eGFR < 60 (16.0%) was more than eGFR >= 60 (5.8%). Median BNP and NT concentrations were elevated in association with decreasing eGFR level. Using receiver-operator characteristic (ROC) analysis, the area under the ROC curve for BNP and NT that stratified subjects with or without heart failure was not different among eGFR level. In conclusion, BNP and NT levels are elevated depend on decreasing eGFR level, BNP and NT are comparable in the accuracy for diagnosing heart failure at every eGFR level. The cut-off value of BNP and NT should be established according to the eGFR level. PMID- 27363217 TI - [Relationship between Clostridium difficile ITS-PCR Type and Pathogenicity]. AB - Clostridium difficile (C. difficile) causes antibiotic-associated diarrhea and nosocomial infection. The PCR of internal transcribed spacer regions (ITS) is easily conductible in a relatively short time. The purpose of the current study is to classify C. difficile by PCR electrophoresis pattern of ITS (ITS-PCR type) and estimate the relationship of the ITS-PCR type of C. difficile with its pathogenicity. We examined 77 strains which were obtained in our hospital from March 2012 to August 2013. Toxin genes were detected by PCR using toxin gene specific primers. Antimicrobial sensitivities were measured by E-test. Pseudomembrane formation and severity of the illness in clinical patients were investigated based on the medical records. The strains were classified into the 33 ITS-PCR types. Among them, most of strains in 18 PCR types were not associated with any toxin genes. Strains with toxin A(+)/B(+)genes were classified into 14PCR types. The 3 strains with toxin B (+) strains and the two strains with toxin A(+)/B(+)/binary toxin(+) genes were classified into 1 PCR type, type 17, and type 16, respectively. 6 strains in 13 strains of type 33, and 5 strains in 11 strains of type 2 were detected from the same ward, presuming nosocomial infection. Minimum inhibitory concentrations (MICs) of vancomycin and metronidazole were <= 2 MUg/mL, distribution of MICs were not correlated with ITS PCR type. The pseudomembrane forming and severity of the illness were not obviously related to ITS-PCR pattern. Thus, the typing of C. difficile by ITS-PCR pattern is considered to be useful for early detection of nosocomial infection, and assessment of toxigenicity. PMID- 27363218 TI - [Analysis of the Squamous Cell Carcinoma Antigen (SCCA) Which Has a Significant Difference in Values between CLIA and FEIA--Case Report of Extra Glycosylation in SCCA]. AB - Squamous cell carcinoma antigen (SCCA) is a glycoprotein that belongs to the serine protease inhibitor family. Clinically, it has been utilized as a tumor marker for squamous cell carcinoma. In clinical laboratories, SCCA is measured by several immunoassays. Recently, a number of studies have been reported that there is a significant difference in values between the immunoassays, attributing to SCCA-immunoglobulin complex. We found a case with significant difference in the SCCA value between CLIA and FEIA. In this case, SCCA-Immunoglobulin complex was not confirmed by gel filtration analysis. Interestingly, 5 to 10 kDa slightly high molecular weight SCCA compared to control was detected by immunoblotting assay. It may be suspected that the aberrant glycosyl modification of SCCA influenced the reactivity to immunoassays. PMID- 27363219 TI - [Reference Intervals of Standard Test Items in Ningen Dock Examination]. AB - OBJECTIVE: Reference intervals (RIs) were derived from records of 1,499,288 individuals who underwent ningen dock examination in 188 institutes which belong to Japan Society of Ningen Dock in 2012. METHODS: Targets were 27 basic laboratory tests, including the body mass index (BMI) and systolic and diastolic blood pressures (SBP, DBP). Individuals fulfilling strict criteria were chosen: SBP < 130, DBP < 85 mmHg, BMI < 25 Kg/m2, non-smoking, ethanol consumption < 20 g/day, under no medication, with no remarkable current/past illness. The latent abnormal values exclusion (LAVE) method was applied to ensure normal results. RLs were derived using a parametric method with modified Box-Cox power transformation. RESULTS: Among all attendees, 23% fulfilled the criteria. Application of the LAVE method further reduced the dataset by 40-50%. RIs without distinction of the sex and age were SBP, DBP, TP, TB, MCV, WBC, and Plt. Sex specific RIs were BMI, CRE, UA, TG, HDL-C, ALT, GGT, Glu, RBC, Hb, and Ht. Age specific RIs in either sex were Alb, AST, HbA1c, TC, LDL-C, FW-LDL-C, nonHDL-C, and ALP. An age-specific RI without distinction of the sex was eGFR. Comparison of derived RIs with clinical decision limits (CDLs) revealed that the upper limits of RIs differed from CDLs according to the sex and age. CONCLUSION: Implementation of sex- and age-related RIs derived from individuals with fully normal ningen dock results will enable the appropriate interpretation of test results in health screening, and promote the effective application of CDLs for therapeutic intervention, taking into account the sex, age, and other health attributes. PMID- 27363220 TI - [The Reliability of Measurement Methods for Medical Examinations and Health Screening]. AB - Clinical laboratory data used in medical examinations and health screening need to have a guaranteed analytical reliability. To ensure the reliability of measurement data, each constituent is required to be compatible with its traceability chain, and any constituent whose traceability chain has yet to be established is required to be appropriately harmonized in the current measurement system. The inter-laboratory reproducibility of standardized measurement values obtained from the external quality assessments conducted by the Japan Medical Association and Japanese Association of Medical Technologists was estimated to evaluate the analytical reliability of clinical tests in Japan. The estimated inter-laboratory reproducibility was then compared with the permissible error limits which have been reported domestically and internationally based on inter- and intra-individual biological variations of healthy subjects. The results showed that most of the measurement uncertainties were sufficiently lower than the permissible limits. This study proposes that the measurement uncertainty of the standardized measurement method has the potential to be a new assessment standard for analytical reliability. PMID- 27363221 TI - [How to Define Significant Changes in Laboratory Test Results in Health Screening]. AB - It is necessary to judge the significance of changes in laboratory test results, especially in health screening. For this purpose, the reference change value (RCV) was proposed, which is the (1- alpha) 100% confidence limit of differences between any two measurements: RCV = ?2 z(alpha) x CV(I), where CV(I) represents intra-individual CV and alpha = 0.05. However, RCV is not commonly employed because: (1) it assumes constant CV(I) regardless of test levels, and (2) it often results in conservative judgements about the changes due to the blind use of 95% as its confidence probability (CP). Recently, we evaluated the level dependency of CV(I) in common laboratory tests and sought an appropriate CP for computing RCV through systematic analysis of a large long-term health-screening database. The dataset used contained data from approximately 14,000 individuals who underwent annual health-checks repeatedly. None of them were taking any medications or showed unnatural changes in BMI. The level of dependency of CV(I) was clearly observed for test items which showed skewed, logarithmic normal distributions but not for those with normal distributions, indicating the need to compute RCV according to the test level for the former items. To assess the choice of practical CP for RCV, we introduced a metabolic syndrome score (sMS) derived by logistic regression analysis. AsMS was used as an external criterion of changes in the nutritional status of individuals in relation to changes in laboratory tests. We evaluated the sensitivity and specificity of RCV at various CPs for detecting significant changes in DeltasMS. The analysis revealed that CP of 80-90% for computing RCV markedly enhanced the sensitivity of detecting DeltasMS without compromising the specificity. We provide a table listing appropriate RCVs for typical levels of common screening tests obtained from the analysis. PMID- 27363222 TI - [Possibility of New Circulating Atherosclerosis-Related Lipid Markers Measurement in Medical and Complete Medical Checkups: Small Dense Low-Density Lipoprotein Cholesterol and Lipoprotein Lipase]. AB - Small dense low-density lipoprotein cholesterol (sdLDL-C) concentrations correlate more strongly with cardiovascular disease (CVD) than other LDL-C and large LDL particle concentrations. Lipoprotein lipase (LPL) plays a central role in triglyceride-rich lipoprotein metabolism by catalyzing the hydrolysis of triglycerides in chylomicrons and very low-density lipoprotein particles and is a useful biomarker in diagnosing Type I, Type IV, and Type V hyperlipidemia. Therefore, the measurement of circulating sdLDL-C and LPL concentrations contributes to the assessment of circulating atherosclerosis-related lipid markers. However, the measurement of these lipids has not been fully adopted in medical and complete medical checkups. Recently, novel automated homogenous assay for measuring sdLDL-C and latex particle-enhanced turbidimetric immunoassay (LTIA) for measuring LPL have been developed, respectively. Using these new assays, sdLDL-C values showed excellent agreement with those obtained by isolation of the d = 1.044 - 1.063 g/mL plasma fraction by sequential ultracentrifugation, and LPL values measured with and without heparin injection were highly correlated with the values measured by the LPL-enzyme-linked immunosorbent assay (ELISA). These assays may be superior to the previous assays for the measurement of sdLDL-C and LPL concentrations due their simplicity and reproducibility. The measurements of sdLDL-C and LPL concentrations may be useful as lipid markers in the assessment of the development and progression of atherosclerosis and the detection of pathological conditions and diseases if these markers are measured in medical and complete medical checkups. We have introduced the possibility of the novel measurement of circulating atherosclerosis-related lipid markers such as sdLDL-C and LPL in medical and complete medical checkups. Further studies are needed to clarify whether sdLDL-C and LPL concentrations are related to the development and progression of atherosclerosis and CVD events. PMID- 27363223 TI - [Utilization of Big Data in Medicine and Future Outlook]. AB - "Big data" is a new buzzword. The point is not to be dazzled by the volume of data, but rather to analyze it, and convert it into insights, innovations, and business value. There are also real differences between conventional analytics and big data. In this article, we show some results of big data analysis using open DPC (Diagnosis Procedure Combination) data in areas of the central part of JAPAN: Toyama, Ishikawa, Fukui, Nagano, Gifu, Aichi, Shizuoka, and Mie Prefectures. These 8 prefectures contain 51 medical administration areas called the second medical area. By applying big data analysis techniques such as k means, hierarchical clustering, and self-organizing maps to DPC data, we can visualize the disease structure and detect similarities or variations among the 51 second medical areas. The combination of a big data analysis technique and open DPC data is a very powerful method to depict real figures on patient distribution in Japan. PMID- 27363224 TI - [Relationship between Coronary Plaque Stability Evaluated by Intravascular Ultrasound and Laboratory Parameters]. AB - Tissue characteristics of coronary plaque have been reported to be associated with cardiovascular events. The stabilization of vulnerable tissue components such as the lipid pool rather than regression of the plaque volume is considered to be of major benefit in the reduction of cardiovascular events. Conventional echocardiography, especially intravascular ultrasound imaging (IVUS), is widely used to determine calcification and the three layers of the arterial wall. However, differentiation of the lipid pool from fibrous tissue using the echo intensity is difficult. Recently, an integrated backscatter (IB) ultrasound technique was developed. The ultrasound IB power ratio is a function of the difference in acoustic characteristic impedance between the medium and target tissue, and the acoustic characteristic impedance is determined by the density of tissue multiplied by the speed of sound. For more comprehensive plaque analysis using IB-IVUS, three-dimensional IB-IVUS offers the potential for the quantitative volumetric tissue characterization of coronary atherosclerosis. Several large clinical trials demonstrated that lipid-lowering therapy with 3 hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) reduces cardiovascular events. The IB techniques provide useful clinical information on the effects of statins and other medications. The presence of lipid-rich plaque is associated with the incidence of atherosclerotic diseases; therefore, ultrasound IB techniques are useful to detect coronary atherosclerotic lesions. PMID- 27363225 TI - [Review of Safety Management from Infection Control Perspectives--Chairmen's Introductory Remarks]. AB - The Japanese Society of Laboratory Medicine has been running its own Medical Safety Committee, and holding a symposium on medical safety during the annual meeting every year. Adopting a team approach to medicine plays a critical role in the development of medical safety culture and advancing medical safety in clinical practice. The infection control team plays a major role in team medical care. This time, the review of safety management from infection control perspective was discussed in the medical safety symposium, which is hoped will help advance medical and patient safety, leading to improvements in the quality of medical care. PMID- 27363226 TI - [Infection Control from the Viewpoint of Medical Safety by Our Clinical Laboratory in TMDU Hospital]. AB - Infection control based on appropriate bacteriological examinations and information is important for medical safety. I present the activities performed by our clinical laboratory in Tokyo Medical and Dental University (TMDU) Hospital. We detected and reported the first Japanese case of KPC-2 carbapenemase producing Klebsiella pneumoniae, of which infection will be a serious problem in the near future in Japan. We examine the antigen and toxins of Clostridium difficile with an immunochromatographic method using not only stool specimens but also the colonies in order to improve the detection rate of the toxins. We perform PCR-based open reading frame typing of methicillin-resistant Staphylococcus aureus for molecular epidemiology. We also contribute to infection control through presenting information such as antibiograms and giving lectures to residents and medical staff. PMID- 27363227 TI - [The Role of the Microbiology Laboratory in Healthcare-Associated Infection Control]. AB - Healthcare-associated infection control aims to protect patients and health care workers from infections. For successful control, it is important not to transmit pathogens and resistant bacteria as well as not to create new resistant bacteria. Preventing the transmission of pathogens and resistant bacteria involves the reliable implementation of preventative measures for specific pathways in response to the causative microorganism. Appropriate information from the microbiology laboratory promotes the thorough implementation of prevention measures. This laboratory also makes it possible to promptly understand data on infections for the whole hospital. Therefore, in addition to the normal reporting of results, surveillance reports of infectious agents, such as drug-resistant bacteria, acid-fast bacilli smear-positive patients, and influenza virus antigen positive patients must be immediately reported to the infection control team (ICT), which is the unit responsible for infection control. In addition, it is important to provide information on the detection of resistant bacteria and antimicrobial susceptibility rates to clinical staff and promote the development of systems in which new resistant bacteria are not created. PMID- 27363228 TI - [Healthcare-Associated Infection Control with Awareness of Patient Safety]. AB - In order to provide safe and secure medical care for patients, health care associated infections (HAI) must not occur. HAI should be considered as incidents, and countermeasures should be viewed as a patient safety management itself. Healthcare-associated infection control (HAIC) is practiced by the infection control team (ICT), which is based on multidisciplinary cooperation. Team members have to recognize that it is the most important to make use of the expertise of each discipline. In addition, all members must try to respond quickly, to help the clinic staff. Visualized rapid information provision and sharing, environmental improvement, outbreak factor analysis, hand hygiene compliance rate improvement, proper antibiotic use (Antimicrobial Stewardship Program: ASP), and regional cooperation & leadership comprise the role of the ICT in the flagship hospital. Regarding this role, we present our hospital's efforts and the outcomes. In conclusion, for medical practice quality improvement, healthcare-associated infection control should be conducted thoroughly along with an awareness of patient safety. PMID- 27363229 TI - Preface. Clinical GI Challenges in the Adolescent. PMID- 27363230 TI - Esophagitis in Adolescents. AB - Esophagitis is the end result of a variety of insults to epithelial homeostasis. Eosinophilic esophagitis is a manifestation of non-IgE-mediated food allergy that most commonly affects the esophagus of males who have other atopic phenomena. Reflux esophagitis reflects repeated exposure to acidic gastric contents because of failure of the normal protections afforded by the LES. Because certain histologic features can be present in either condition, endoscopic biopsy alone does not distinguish them. Their symptoms overlap, but the treatment options are very different, such that making a formal diagnosis by following consensus guidelines is essential. A treatment protocol designed to manage the inflammation by controlling the provocative factors (acid for GERD and food antigens for EoE) or suppressing the inflammation (ie, topical steroids for EoE) should result in normalization of the mucosa and resolution of symptoms. Eosinophilic esophagitis is a chronic condition that rarely remits spontaneously, so any therapeutic modality will need to be continued indefinitely. PMID- 27363231 TI - Celiac Disease, Wheat Allergy, and Non-Celiac Gluten Sensitivity: What's the Difference? PMID- 27363232 TI - Advances in Pain-Predominant Functional Gastrointestinal Disorders in the Adolescent. PMID- 27363233 TI - Advances in Pediatric Inflammatory Bowel Disease. PMID- 27363234 TI - Liver Disease in Adolescents. PMID- 27363235 TI - Gastrointestinal Conditions in the Obese Patient. AB - Obesity in adolescents presents many challenges for the patient, family, and physician. The myriad problems involving the GI tract will be managed more effectively when the treating physician has an understanding of the presentations, pathophysiology, appropriate laboratory evaluation, and approaches to treatment for these complications. In addition to being familiar with the pharmacotherapeutic options available, having an approach to behavioral change, such as MI, can be an extremely useful tool. PMID- 27363236 TI - Contemporary Dietary Practices: FODMAPs and Beyond. AB - There is no diet that is recommended for all individuals. Some special diets (eg, gluten-free for celiac disease) are necessary for health and quality of life. Other diets may be recommended for a short period of time to aid in symptom relief but may not be recommended for the long- term (eg, LFD). Popular diets continue to come and go with varying levels of success. When considering adolescents, continued growth and development are most important, and restrictive diets can lead to nutrient inadequacies and poor growth. Before making any recommendation, it is important to consider the goal of the diet and the cost versus benefits associated with following the diet. Adherence is always a challenge, regardless of the type of diet implemented. If a special diet is not warranted for the health, safety, and desired quality of life of the individual, it should not be implemented. PMID- 27363237 TI - Vitamin D in Health and Disease in Adolescents: When to Screen, Whom to Treat, and How to Treat. AB - The existing guidelines on screening and treatment are confusing because different guidelines target different populations. The IOM and AAP guidelines target generally healthy populations, whereas the Endocrine Society and other subspecialty guidelines target individuals with specific medical conditions associated with increased bone fragility. These distinctions have not always been well articulated. For healthy adolescents, the AAP does not recommend universal screening or screening of obese or dark-skinned individuals. Increased dietary intake of vitamin D is recommended, and vitamin D supplementation can be considered if the RDA cannot be met. For adolescents with chronic medical illnesses associated with increased fracture risk, screening for vitamin D deficiency should be performed by obtaining a serum 25-OHD level. Those found to be deficient (25-OHD level < 20 ng/mL) should be treated with doses of vitamin D2 or vitamin D3 higher than the daily requirement (as discussed in the section on vitamin D and chronic disease), followed by a maintenance dose. A repeat 25-OHD level should be obtained after the therapeutic course is completed. Some experts advocate for achievement of 25-OHD levels greater than 30 ng/mL in conditions associated with increased bone fragility, and several pediatric subspecialty organizations have made recommendations specific to the diseases they treat. In such instances, the recommendations of the pediatric subspecialty organizations should take precedence over the AAP recommendations for adolescents with chronic illnesses associated with increased bone fragility because the AAP recommendations were primarily targeted at a healthy population. PMID- 27363238 TI - The Gut Microbiome and Probiotics. PMID- 27363239 TI - Gastrointestinal Issues in Adolescents with Eating Disorders. PMID- 27363240 TI - Health Care Maintenance in Adolescents with Inflammatory Bowel Disease. PMID- 27363241 TI - Transition from Pediatric to Adult Centered Care: Lessons from the Literature and the Trenches. PMID- 27363242 TI - [Anatomical collections and exhibition regimes. An introduction]. PMID- 27363243 TI - [Modelling science. The ceroplastics of Ignacio Lacaba in the Colegio de Cirugia de San Carlos, Madrid]. AB - Models made of wax had enormous diffusion in the anatomical teaching of the 18th century. It transcended the borders of a science that impregnated with scientific knowledge the artistic expression of beauty. Based on this premise, the San Carlos Royal College of Surgery created in Madrid a large collection of anatomical models, which is currently maintained by the Javier Puerta Anatomy Museum in the School of Medicine at Madrid Complutense University. The collection began in 1786 with Ignacio Lacaba, the first dissector of the Surgery College of Madrid, whose artistic sensibility and deep knowledge of anatomy contributed and facilitated harmonization between the work of the wax sculptors and language and anatomical expression. PMID- 27363244 TI - The spatial rhetoric of Gustav Zeiller's popular anatomical museum. AB - This article focuses on the public experience of science by studying the exhibition practice of a small popular anatomy museum. The owner, Gustav Zeiller, a little-known German model maker and entrepreneur, opened his private collection in Dresden in 1888 with the aim of providing experts and laymen alike with a scientific education on bodily matters and health care. The spatial configuration of his museum environment turned the wax models into didactic instruments. Relying on the possible connexion between material culture studies and history of the emotions, this article highlights how Zeiller choreographed the encounter between the museum objects and its visitors. I argue that the spatial set up of his museum objects entailed rhetorical choices that did not simply address the social utility of his museum. Moreover, it fulfilled the aim of modifying the emotional disposition of his intended spectatorship. I hope to show that studying the emotional responses toward artefacts can offer a fruitful approach to examine the public experience of medicine. PMID- 27363245 TI - [Divine cadavers: gender, medical discourse, and anatomical collections in the legend of Pedro Gonzalez de Velasco]. AB - This paper examines the relationship between the public image of Pedro Gonzolez de Velasco (1815-1882), famous for his anatomical collections and his Anthropological Museum, founded in 1875 in Madrid, and the popular legend related to the death, embalming and exhumation of his daughter Concepcion. The doctor who is committed to the nation becomes a mad scientist, and his official biography is transformed into an urban legend. Beyond the merely anecdotal, I show how the aesthetics associated with female corpses and artificial women organize cultural imaginaries, bringing together medical discourses and literary and artistic representations. PMID- 27363246 TI - Pathological anatomy and self-portraiture. AB - Why should an artist look to anatomical or pathological specimens as a reservoir of images with which to facilitate an articulation of his or her own artistic or personal identity? This is the starting point of a reflection on the disappearance of the artist and its transformation into a passive object. As a result, it is also a reflection into the blurring lines between subject and object. On the grounds of the work elaborated by the artist Lisa Temple-Cox and the critical look and comments made by the observer Harcourt, this paper is a first-hand attempt to understand the configuration of the self and the influence of the artistic intervention in the generation and representation of anatomical knowledge, resulting in an exploration into the intertwined processes that create both historical subjects and historical objects. PMID- 27363247 TI - [Medical expert reports in the Valencia of the late Middle Ages: cases of poisoning]. AB - During the last decades of the 13th century, in the midst of the shaping and medicalization of the new Kingdom of Valencia, the authorities and citizens envisaged the role that physicians could have in clarifying violent deaths. The first circumstance that compelled judges to resort to physicians was the possible poisoning of an individual, given that they could contribute to elucidating the truth with their expert knowledge. They were even requested to use post-mortem dissection if necessary for this purpose. In reality, physicians were conscious of their limitations in this field and the need for them to act with caution. PMID- 27363248 TI - [Barbers, charlatans, and the sick: The medical plurality of baroque Spain perceived by the picaresque Estebanillo Gonzalez]. AB - In order to know about diseases and their medical treatment from the perspective of the patient in Baroque Spanish society, creative literature, especially the picaresque novel, is a valuable source that offers a representation of ideas on medicine and disease that were widespread among the population and difficult to access from other sources. The first-person narrative in the Vida y hechos de Estebanillo Gonzalez (1646) offers knowledge on three different aspects of the medical world in Europe during the Thirty Years' War: Estebanillo practises various medical professions, appears in the story as a patient and comments on health practices and disease, providing highly useful material to analyze how different fields of medicine are represented in this literary work. PMID- 27363249 TI - [Female students in internships in Parisian hospitals (1871-1910). Exclusion and inclusion processes]. AB - This study addresses the explicit and implicit exclusion mechanisms that limited the access of women to internships in Paris hospitals during the last decades of the 19th century through examination of the documentation generated in the admission process and the texts of female physicians who supported their access. In response to the applications of female medical students to register for the admission tests, the Conseil de Surveillance de l'Assistance Publique delayed their entry for some years until their registration was finally permitted. However, their inclusion in the institution did not produce integration because of the multiple dimensions of the exclusion mechanisms. PMID- 27363250 TI - [The <> and beginnings of Chilean endocrinology in the 1920s]. AB - Rejuvenation was a chapter of critical importance for the worldwide development of endocrinology in the 1920s. This work explores the acceptance of these techniques in Chile. Starting in the late 19th century, the Chilean Medical Journal (Revista Medica de Chile) incorporated references to experiments with endocrine gland preparations that were being conducted in Europe at the time. An appropriation of the experiments by the Austrian Eugen Steinach began in 1920, with prominent figures such as the Italian professor Juan Noe Crevani and the young Chilean student Ottmar Wilhelm. Between 1922 and 1924, Wilhelm developed a series of experiments on dogs, bulls, pigs, rats and Welfare Board patients through the so-called Steinach operation, which consisted of the sectioning of the efferent channel in one of the testicles. Professor Noe's scientific patronage policy and Wilhelm's strategy of succession in the field led the latter to hold a chair in the new School of Medicine of Universidad de Concepci6n at the age of 25. From this position, the. figure of Wilhelm was fundamental for the development of a line of endocrinological research that was able to position Universidad de Concepci6n as a scientific development centre, which was strengthened by the arrival of another disciple of Steinach in Chile, the Latvian professor Alejandro Lipschutz. PMID- 27363251 TI - [<>: an expert report by Dr. Egas Moniz on homosexuality]. AB - At the beginning of the 20th century, the noted Nobel prize-winning Portuguese neurologist Egas Moniz made an expert analysis on homosexuality in a marriage annulment case of major value as an example of the effective application of sexological knowledge of that period. Contemporary republican legislation established marriage annulment in medical terms and punished relations between persons of the same sex, or contra natura. In his report, Moniz attempted to interpret distinctive elements of the life of the subject using sexological categories, illustrating the interaction between these categories and the changing forms adopted by homosexuality (or homosexual people) of the time. PMID- 27363252 TI - The Status of the Initial Rise as a Marker of Focus in French. AB - This study addresses the relationship between information structure and intonation in French. Using an interactive speech production experiment, it tests the hypothesis that the French initial rise (LHi) is used to mark the left edge of a contrastively focused constituent. Since the occurrence of the initial rise is also known to be sensitive to the length of an Accentual Phrase (AP), AP length was manipulated within the same experiment in a 2 x 2 design. This made it possible to explore the issue of whether the initial rise represents a true marker of focus in the traditional sense, or whether the association is less direct. The results show that focus and phrase length make contributions to the distribution of the initial rise, but with no interaction. It is argued that these findings are incompatible with a model that assumes a direct mapping between focus and the initial rise, and that the relatively weak association can nevertheless be informative in a model of interpretation that integrates multiple probabilistic inputs to initial rise occurrence. These findings represent the first quantitative experimental assessment of focus realization in French in a non-corrective context, and establish a previously undocumented link between the initial rise and discourse-level meaning. PMID- 27363253 TI - The Time Course for Processing Vowels and Lexical Tones: Reading Aloud Thai Words. AB - Three naming aloud experiments and a lexical decision (LD) experiment used masked priming to index the processing of written Thai vowels and tones. Thai allows for manipulation of the mapping between orthography and phonology not possible in other orthographies, for example, the use of consonants, vowels and tone markers in both horizontal and vertical orthographic positions (HOPs and VOPs). Experiment I showed that changing a vowel between prime and target slowed down target naming but changing a tone mark did not. Experiment I used an across item design and a different number of HOPs in the way vowels and tones were specified. Experiment 2 used a within-item design and tested vowel and tone changes for both 2-HOP and 3-HOP targets separately. The 3-HOP words showed the same tone and vowel change effect as Experiment 1, whereas 2-HOP items did not. It was speculated that the 2-HOP result was due to the variable position of the vowel affecting priming. Experiment 3 employed a more stringent control over the 2-HOP vowel and tone items and found priming for the tone changes but not for vowel changes. The final experiment retested the items from Experiment 3 with the LD task and found no priming for the tone change items, indicating that the tone effect in Experiment 3 was due to processes involved in naming aloud. In all, the results supported the view that for naming a word, the development of tone information is slower than vowel information. PMID- 27363254 TI - Is Language a Factor in the Perception of Foreign Accent Syndrome? AB - Neurogenic foreign accent syndrome (FAS) is diagnosed when listeners perceive speech associated with motor speech impairments as foreign rather than disordered. Speakers with foreign accent syndrome typically have aphasia. It remains unclear how far language changes might contribute to the perception of foreign accent syndrome independent of accent. Judges with and without training in language analysis rated orthographic transcriptions of speech from people with foreign accent syndrome, speech-language disorder and no foreign accent syndrome, foreign accent without neurological impairment and healthy controls on scales of foreignness, normalness and disorderedness. Control speakers were judged as significantly more normal, less disordered and less foreign than other groups. Foreign accent syndrome speakers' transcriptions consistently profiled most closely to those of foreign speakers and significantly different to speakers with speech-language disorder. On normalness and foreignness ratings there were no significant differences between foreign and foreign accent syndrome speakers. For disorderedness, foreign accent syndrome participants fell midway between foreign speakers and those with speech-language impairment only. Slower rate, more hesitations, pauses within and between utterances influenced judgments, delineating control scripts from others. Word-level syntactic and morphological deviations and reduced syntactic and semantic repertoire linked strongly with foreignness perceptions. Greater disordered ratings related to word fragments, poorly intelligible grammatical structures and inappropriate word selection. Language changes influence foreignness perception. Clinical and theoretical issues are addressed. PMID- 27363255 TI - Dutch and German 3-Year-Olds' Representations of Voicing Alternations. AB - The voicing contrast is neutralized syllable and word finally in Dutch and German, leading to alternations within the morphological paradigm (e.g., Dutch 'bed(s)', be[t]-be[d]en, German 'dog(s)', Hun[t]-Hun[d]e). Despite structural similarity, language-specific morphological, phonological and lexical properties impact on the distribution of this alternation in the two languages. Previous acquisition research has focused on one language only, predominantly focusing on children's production accuracy, concluding that alternations are not acquired until late in the acquisition process in either language. This paper adapts a perceptual method to investigate how voicing alternations are represented in the mental lexicon of Dutch and German 3-year-olds. Sensitivity to mispronunciations of voicing word-medially in plural forms was measured using a visual fixation procedure. Dutch children exhibited evidence of overgeneralizing the voicing alternation, whereas German children consistently preferred the correct pronunciation to mispronunciations. Results indicate that the acquisition of voicing alternations is influenced by language-specific factors beyond the alternation itself. PMID- 27363256 TI - When pitch Accents Encode Speaker Commitment: Evidence from French Intonation. AB - Recent studies on a variety of languages have shown that a speaker's commitment to the propositional content of his or her utterance can be encoded, among other strategies, by pitch accent types. Since prior research mainly relied on lexical stress languages, our understanding of how speakers of a non-lexical-stress language encode speaker commitment is limited. This paper explores the contribution of the last pitch accent of an intonation phrase to convey speaker commitment in French, a language that has stress at the phrasal level as well as a restricted set of pitch accents. In a production experiment, participants had to produce sentences in two pragmatic contexts: unbiased questions (the speaker had no particular belief with respect to the expected answer) and negatively biased questions (the speaker believed the proposition to be false). Results revealed that negatively biased questions consistently exhibited an additional unaccented F0 peak in the preaccentual syllable (an H+!H* pitch accent) while unbiased questions were often realized with a rising pattern across the accented syllable (an H* pitch accent). These results provide evidence that pitch accent types in French can signal the speaker's belief about the certainty of the proposition expressed in French. It also has implications for the phonological model of French intonation. PMID- 27363257 TI - The Fitbit Fault Line: Two Proposals to Protect Health and Fitness Data at Work. AB - Employers are collecting and using their employees' health data, mined from wearable fitness devices and health apps, in new, profitable, and barely regulated ways. The importance of protecting employee health and fitness data will grow exponentially in the future. This is the moment for a robust discussion of how law can better protect employees from the potential misuse of their health data. While scholars have just begun to examine the problem of health data privacy, this Article contributes to the academic literature in three important ways. First, it analyzes the convergence of three trends resulting in an unprecedented growth of health-related data: the Internet of Things, the Quantified Self movement, and the Rise of Health Platforms. Second, it describes the insufficiencies of specific data privacy laws and federal agency actions in the context of protecting employee health data from employer misuse. Finally, it provides two detailed and workable solutions for remedying the current lack of protection of employee health data that will realign employer use with reasonable expectations of health and fitness privacy. The Article proceeds in four Parts. Part I describes the growth of self-monitoring apps, devices, and other sensor enabled technology that can monitor a wide range of data related to an employee's health and fitness and the relationship of this growth to both the Quantified Self movement and the Internet of Things. Part II explains the increasing use of employee monitoring through a wide range of sensors, including wearable devices, and the potential uses of that health and fitness data. Part III explores the various regulations and agency actions that might protect employees from the potential misuse of their health and fitness data and the shortcomings of each. Part IV proposes two specific measures that would help ameliorate the ineffective legal protections that currently exist in this context. In order to improve employee notice of and control over the disclosure of their health data, I recommend the adoption of a mandatory privacy labeling law for health-related devices and apps to be enacted and enforced by the Federal Trade Commission (FTC). As a complementary measure, I also recommend that be amended so that its protections extend to the health-related data that employers may acquire about their employees. The Article concludes with suggestions for additional scholarly discussion. PMID- 27363258 TI - Health and Taxes: Hospitals, Community Health and the IRS. AB - The Affordable Care Act created new conditions of federal tax exemption for nonprofit hospitals, including a requirement that hospitals conduct a community health needs assessment (CHNA) every three years to identify significant health needs in their communities and then develop and implement a strategy responding to those needs. As a result, hospitals must now do more than provide charity care to their patients in exchange for the benefits of tax exemption. The CHNA requirement has the potential both to prompt a radical change in hospitals' relationship to their communities and to enlist hospitals as meaningful contributors to community health improvement initiatives. Final regulations issued in December 2014 clarify hospitals' obligations under the CHNA requirement, but could do more to facilitate hospitals' engagement in collaborative community health projects. The Internal Revenue Service (IRS) has a rich opportunity, while hospitals are still learning to conduct CHNAs, to develop guidance establishing clear but flexible expectations for how providers should assess and address community needs. This Article urges the IRS to seize that opportunity by refining its regulatory framework for the CHNA requirement. Specifically, the IRS should more robustly promote transparency, accountability, community engagement, and collaboration while simultaneously leaving hospitals a good degree of flexibility. By promoting alignment between hospitals' regulatory compliance activities and broader community health improvement initiatives, the IRS could play a meaningful role in efforts to reorient our system towards promoting health and not simply treating illness. PMID- 27363259 TI - The Antidotes to the Double Standard: Protecting the Healthcare Rights of Mentally Ill Inmates by Blurring the Line Between Estelle and Youngberg. AB - This Note is an examination of mentally ill inmates' constitutional right to treatment. It has significant doctrinal and practical implications. In terms of doctrine, the Supreme Court has created distinct standards for the minimum levels of care for inmates (Estelle) and the civilly committed mentally ill (Youngberg). Under this framework mentally ill inmates are constitutionally equivalent to inmates generally, but are entitled to less care than the civilly committed even if they suffer the same illness. This Note explores this gap through the lens of equal protection and argues that mentally ill inmates are similarly situated to the civilly committed. It further contends that inmates constitute a "discrete and insular minority" and thus the standard establishing their right to care should be subject to strict scrutiny. This Note finds that Estelle fails this test. Practically, this Note brings visibility to a consequential area of the law neglected by scholarship. Over half of inmates are mentally ill and yet treatment in prisons is inadequate. The literature at the intersection of health, criminal justice, and constitutional rights has not constructively considered how doctrine should be changed to protect the wellbeing of this vulnerable population. Scholars have also provided little oversight of the judicial administration of justice in this field; there are few reviews of how judges actually apply treatment rights standards. This Note lessens this blind spot by exposing how courts fail to properly distinguish between different standards. This Note proposes that the most promising antidote to the Estelle-Youngberg double standard, counterintuitively, is not the creation of a uniform standard. A standard that puts mentally ill inmates on equal footing with the civilly committed would solve the doctrinal puzzle, but would be subject to Youngberg's inherent flaws and the judicial malpractice in this area. Recognizing the deficiencies of a purely judicial remedy, this Note recommends a solution relying both on courts and Congress. It concludes by highlighting the importance of targeting the primary causes of society's neglect of mentally ill inmates--the stigmatization of mental illness and incarceration--as a necessary step in spurring these institutions to action. Vindication of mentally ill inmates' right to treatment requires that society first overcome its prejudice against this vulnerable population. PMID- 27363260 TI - How PBDEs Are Transformed into Dihydroxylated and Dioxin Metabolites Catalyzed by the Active Center of Cytochrome P450s: A DFT Study. AB - Predicting metabolism of chemicals and potential toxicities of relevant metabolites remains a vital and difficult task in risk assessment. Recent findings suggested that polybrominated diphenyl ethers (PBDEs) can be transformed into dihydroxylated and dioxin metabolites catalyzed by cytochrome P450 enzymes (CYPs), whereas the mechanisms pertinent to these transformations remain largely unknown. Here, by means of density functional theory (DFT) calculations, we probed the metabolic pathways of 2,2',4,4'-tetraBDE (BDE-47) using the active center model of CYPs (Compound I). Results show that BDE-47 is first oxidized to monohydroxylated products (HO-BDEs), wherein a keto-enol tautomerism is identified for rearrangement of the cyclohexenone intermediate. Dihydroxylation with HO-BDEs as precursors, has a unique phenolic H-abstraction and hydroxyl rebound pathway that is distinct from that for monohydroxylation, which accounts for the absence of epoxides in in vitro studies. Furthermore, we found only dihydroxylated PBDEs with heterophenyl -OH substituents ortho- and meta- to the ether bond serve as precursors for dioxins, which are evolved from aryl biradical coupling of diketone intermediates that are produced from dehydrogenation of the dihydroxylated PBDEs by Compound I. This study may enlighten the development of computational models that afford mechanism-based prediction of the xenobiotic biotransformation catalyzed by CYPs. PMID- 27363261 TI - Changes in lactate dehydrogenase are associated with central gray matter lesions in newborns with hypoxic-ischemic encephalopathy. AB - PURPOSE: Biomarkers may predict neurological prognosis in infants with hypoxic ischemic encephalopathy (HIE). We evaluated the relationship between serum lactate dehydrogenase (LDH) and brain magnetic resonance imaging (MRI), which predicts neurodevelopmental outcomes, in order to assess whether LDH levels are similarly predictive. MATERIALS AND METHODS: Medical records were reviewed for infants with HIE and LDH levels were assessed on the first (LDH1) and third (LDH3) days following birth. Receiver operating characteristic curves were obtained in relation to central gray matter hypoxic-ischemic lesions. RESULTS: Of 92 patients, 52 (56.5%) had hypoxic-ischemic lesions on brain MRI, and 21 of these infants (40.4%) had central gray matter lesions. LDH1 and LDH3 did not differ; however, the percentage change (DeltaLDH%) was significantly higher in infants with central gray matter lesions (36.9% versus 6.6%, p = 0.006). With cutoffs of 187 (IU/L, DeltaLDH) and 19.4 (%, DeltaLDH%), the sensitivity, specificity, positive predictive value and negative predictive value were 71.4, 69.0, 40.5 and 89.1%, respectively. The relative risk was 5.57 (p = 0.001). CONCLUSION: Changes in serum LDH may be a useful biomarker for predicting future neurodevelopmental prognosis in infants with HIE. PMID- 27363262 TI - [Endogenous IFN-beta maintains M1 polarization status and inhibits proliferation and invasion of hepatocellular carcinoma cells]. AB - Objective To investigate the effect of endogenous interferon beta (IFN-beta) on the polarization of M1 macrophages as well as the proliferation and invasion activities of hepatocellular carcinoma cells (HCCs) mediated by M1 macrophages. Methods U937-M1 macrophages derived from human monocytic tumor cells U937 was established and the cell phenotypes were identified by real-time quantitative PCR, ELISA and flow cytometry. After IFN-beta gene was knocked down with siRNA or IFN-beta was neutralized with IFN-beta monoantibody in U937-M1 macrophages, the change of M1/M2 phenotype was again analyzed by the above methods. The expressions of interferon regulatory factor 1 (IRF1) and IRF5 were detected by real-time quantitative PCR and Western blotting. The proliferation and invasion activities of HCCs, which were cultured with conditioned medium (CM) collected from different macrophage groups, were analyzed by CCK-8 assay and Transwell(TM) experiments, respectively. Results U937-M1 macrophages showed higher expressions of interleukin 12p35 (IL-12p35), interleukin 12p40 (IL-12p40), interleukin 12p70 (IL-12p70), interleukin 23p19 (IL-23p19), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and CD86 than U937-M0 did. But both U937-M0 macrophages and U937-M1 macrophages showed low expression of CD206. However, compared with the U937-M1 macrophages, the IFN-beta-blocked U937-M1 macrophages presented decreased expressions of the above M1 macrophages-associated markers, but increased expressions of M2 macrophages-associated markers IL-10 and CD206, as well as lower expressions of IRF1 and IRF5. The inhibited proliferation/invasion activities of HCCs mediated by U937-M1 macrophages were reversed by IFN-beta blocked U937-M1 macrophages. Conclusion Blocking endogenous IFN-beta could inhibit the U937-M1 polarization status and U937-M1 macrophages-mediated anti tumor activity of HCCs. IFN-beta might be involved in modulating the expressions of IRF1 and IRF5 as well as maintaining the M1 polarization status and its function. PMID- 27363264 TI - [Combination of TLR7 agonist T7-ethacrynic acid conjugate with ROR1 has a stronger anti-breast cancer effect]. AB - Objective To investigate the synergistic anti-breast cancer effect of Toll-like receptor 7 agonist T7-ethacrynic acid conjugate (T7-EA) in combination with receptor-tyrosine-kinase-like orphan receptor 1 (ROR1). Methods ROR1 cytotoxic T lymphocyte (CTL) epitope was predicted using Syfpeithi online software. Mouse spleen lymphocytes and bone marrow dendritic cells (DCs) were separately stimulated with 4 MUmol/L T7-EA and 4 MUmol/L ROR1 alone or in combination. ELISA assay was used to measure the levels of interferon-gamma (IFN-gamma), interleukin 12 (IL-12) and tumor necrosis factor-alpha (TNF-alpha). Xenograft model was established via subcutaneous injection of mouse breast cancer 4T1 cells. The mice were weekly treated through intraperitoneal administration of 3 mg/kg T7-EA, 15 mg/kg ROR1 or the combination of T7-EA and ROR1. After four rounds of treatment, tumor tissues were weighed. Serum level of anti-4T1 tumor protein IgG was measured by ELISA. Specific CTL activity was detected by lactate dehydrogenase (LDH) assay. Results The peptide PYCDETSSV was chosen as an antigen epitope of breast cancer. The T7-EA highly activated in vitro lymphocytes in a dose dependent manner, which wasn't affected by other relevant peptides. The combination of T7-EA and ROR1 stimulated the secretion of IFN-gamma and IL-12 by lymphocytes and TNF-alpha by bone marrow DCs. The growth of tumor in vivo was significantly inhibited by T7-EA combined with ROR1 compared with T7-EA or ROR1 alone. The specific CTL activity triggered by T7-EA combined with ROR1 was much stronger than that triggered by T7-EA or ROR1 alone. The titer of anti-4T1 tumor protein IgG induced by T7-EA combined with ROR1 was higher than that induced by T7-EA or ROR1. Conclusion The combination of T7-EA and ROR1 has a better killing effect on breast cancer. PMID- 27363263 TI - [IL-12 induces autophagy via AKT/mTOR/STAT3 signaling pathway in human hepatoma cells]. AB - Objective To investigate the effect of IL-12 on autophagy and the relative possible mechanism in HepG2 and SMMC-7721 human hepatoma cells. Methods The hepatoma cells were treated with IL-12 (10 ng/mL) for 6 hours. Western blotting was applied to detect the expressions of microtubule-associated protein 1 light chain 3 (LC-3), Beclin 1 and the phosphorylated levels of protein kinase B (AKT), mammalian target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3); immunofluorescence assay (IFA) and transmission electron microscopy (TEM) were used to observe the formation of autophagosome. After STAT3 was inhibited by STATTIC or siSTAT3 and AKT was activated by insulin-like growth factor (IGF-1), Western blotting and IFA were performed again to analyze the change of IL-12-induced autophagy. After the cells were treated with IL-12 (10 ng/mL) for 1, 2, 3, 4, 5 days, CCK-8 assay was used to determine the growth ability. After the hepatoma cells were treated with IL-12 (10 ng/mL) for 48 hours, trypan blue staining was used to detect the death rate of the cells. After cell autophagy was inhibit by siBeclin 1, CCK-8 assay and trypan blue staining were performed again to study the effect of IL-12 on the proliferation and death of human hepatoma cells. Results IL-12 induced autophagy and inhibited cell growth in the hepatoma cells. Silencing Beclin 1 gene enhanced IL-12-mediated growth inhibition and cell death. Furthermore, IL-12 treatment also decreased the expressions of p-AKT, p-mTOR and p-STAT3. The pretreatment of siSTAT3 or STATTIC inhibited STAT3-enhanced IL-12-induced autophagy. Accordingly, activation of AKT with IGF-1 decreased IL-12-induced autophagy. Conclusion IL-12 could induce autophagy through AKT/mTOR/STAT3 signaling pathways and the induction of autophagy attenuates the growth-inhibitory effect of IL-12 on hepatoma cells. PMID- 27363265 TI - [Total flavones derived from Lagotis brevituba maxim reduce the levels of inflammatory cytokines in cerebral cortex and hippocampus of Alzheimer's disease mice]. AB - Objective To investigate the mechanism behind the treatment of Alzheimer's disease (AD) with total flavones derived from Lagotis brevituba maxim (TF-LBM). Methods Fifty SAMP8 mice (aged 8 months) were randomly divided into 5 groups, (150, 300, 600) mg/kg TF-LBM groups, 0.65 g/kg donepezil HCl group and AD model group; 10 SAMR1 mice (aged 8 months) were used as a control group of normal aging. The AD model group and the normal aging control group were given the same volume of distilled water as TF-LBM groups. Eight weeks after intragastric administration, Morris water maze experiment was conducted to calculate the latency of place navigation. After the behavioral experiment, the brain cortical tissue and hippocampus (CA1 region) of the mice from various groups were taken to observe the morphological changes of the cortical tissue and hippocampus and test IL-1beta, IL-6, TNF-alpha content. Results Compared with the model group, the escape latency of the normal aging group, the high-dose TF-LBM group and the donepezil HCl group were evidently shortened; compared with the normal aging group, IL-1beta, IL-6, TNF-alphaof the model group increased significantly; compared with the model group, IL-1beta content of the low-dose TF-LBM group had no obvious difference, while IL-1beta content of the median-dose and high-dose TF LBM groups and the donepezil HCl group decreased significantly; IL-6 content decreased in all TF-LBM groups and the donepezil HCl group; TNF-alpha level in the low-dose and median-dose TF-LBM groups had no evident difference, while it was reduced significantly in the high-dose TF-LBM group and the donepezil HCl group. Compared with the normal aging group, IL-1beta, IL-6 and TNF-alpha content of the model group increased significantly; compared with the model group, IL 1beta, IL-6 and TNF-alpha content of all TF-LBM groups and the donepezil HCl group decreased. Conclusion TF-LBM can improve the behavior change of SAMP8 mice with AD. TF-LBM can reduce the content of IL-6, IL-1beta and TNF-alpha in cerebral cortex and hippocampus CA1. PMID- 27363266 TI - [Down-regulation of TIPE2 promotes the proliferation and immune activity of T lymphocytes]. AB - Objective To utilize specific small interfering RNA (siRNA) to silence the expression of tumor necrosis factor alpha-induced protein 8 like-2 (TIPE2) gene of T lymphocytes and investigate the effect of TIPE2 targeting siRNA on T lymphocyte proliferation and immune function. Methods Mouse spleen T lymphocytes were sorted by magnetic beads. Western blotting was used to screen and validate an effective siRNA to silence the TIPE2 gene expression of T lymphocytes. Twenty four hours after transfection with the siRNA into T lymphocytes, the expression of CD69 in each group was detected by flow cytometry. Seventy-two hours after transfection, the proliferation of the T lymphocytes was measured with CCK-8 assay; meanwhile, the secretion levels of interleukin 2 (IL-2) and interferon gamma (IFN-gamma) in each group were measured by ELISA. Results We obtained TIPE2 targeting siRNA sequences and effectively silenced the expression of TIPE2 gene. After TIPE2 gene expression was down-regulated, the expression of the CD69 on T lymphocytes increased, and the proliferation of T lymphocytes and the secretion of IL-2 and IFN-gamma were enhanced. Conclusion Down-regulation of TIPE2 gene expression can promote the T lymphocyte proliferation and immune activity. PMID- 27363267 TI - [Naringin againsts learning and memory dysfunction of rats induced by intraventricular perfusion with HIV-1 glycoprotein 120 (gp120)]. AB - Objective To explore the protective effect of naringin on cognitive disorders induced by HIV-1-enveloped glycoprotein 120 (gp120) mediated by the P2X7 receptor in rats. Methods The Morris water maze (MWM) test was used to evaluate the effect of naringin on cognitive dysfunction induced by gp120 intraventricular perfusion in the rat models of dementia. The expression levels of P2X7 receptor mRNA and protein in hippocampus tissues were detected by reverse transcription PCR (RT PCR) and Western blotting, respectively. Results The MWM test showed that compared with the gp120 model group, the naringin treatment group showed significantly faster escape latencies and reduced searching target errors. RT-PCR and Western blotting showed that the expressions of P2X7 receptor mRNA and protein were reduced in the hippocampus of rats in the naringin treatment group compared with the gp120 model group. Conclusion Naringin may againsts learning and memory dysfunction induced by gp120, which may counter the up-regulated expression of the P2X7 receptor in the hippocampus of rats. PMID- 27363268 TI - [Hypoxia combined with TNF-alpha induces apoptosis of cultured human pulmonary microvascular endothelial cells via activation of the STAT3 rather than ERK1/2 signaling pathway]. AB - Objective To explore the effect of combined hypoxia and tumor necrosis factor alpha (TNF-alpha) on the apoptosis of human pulmonary microvascular endothelial cells (HPMVECs) and the involved signaling pathway mechanism. Methods Some HPMVECs were treated with hypoxia within 6, 12, or 24 hours, and the other cells were treated with TNF-alpha at the concentrations of 10, 20, 50, or 100 ng/mL. Cell activity was determined by MTT assay in each group to determine the best combined stimulatory conditions. Under the optimal costimulatory condition, the activity of caspase-3 was detected by flow cytometry, annexin V-FITC/PI double staining combined with flow cytometry was used to detect the apoptosis, Western blotting was performed to test the level of phosphorylated signal transducer and activator of transcription 3 (pSTAT3) and phosphorylated extracellular signal regulated kinase 1/2 (pERK1/2). Results The cell activity was the lowest in 24 hour hypoxia group and 100 ng/mL TNF-alpha group. Therefore, we confirmed the combination of hypoxia for 24 hours and 100 ng/mL TNF-alpha as the costimulatory conditions. The caspase-3 activity and apoptosis rate in the combined treatment group were higher, compared with the other groups. The expression of pSTAT3, rather than pERK1/2, increased in the combined treatment group, compared with the control group. Moreover, the STAT3 inhibitor S3I-201 reduced the apoptosis rate in the combined treatment group. Conclusion Combined hypoxia and TNF-alpha could promote HPMVEC apoptosis by activating STAT3 rather than ERK1/2. PMID- 27363269 TI - [Interferon-beta combined with all-trans retinoic acid supresses proliferation and promote apoptosis by inhibiting JAK2/STAT3 pathway in HepG2 human hepatocellular carcinoma cells]. AB - Objective To investigate the effect of interferon-beta (IFN-beta) combined with all-trans retinoic acid (ATRA) on the proliferation and apoptosis of HepG2 human hepatocarcinoma cells and the role of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signal pathway in the process. Methods HepG2 cells were randomly divided intro three groups and treated with 1000 U/mL IFN-beta, 10 MUmol/L ATRA and 1000 U/mL IFN-beta combined with 10 MUmol/L ATRA, respectively for 24 hours. Cell viability was measured by MTT assay and apoptosis rate was detected by flow cytometry. Western blotting was applied to detect the protein levels of p-JAK2, p-STAT3, gene associated with retinoid-interferon induced mortality-19 (GRIM-19), Bcl-2, Bcl-xl and Bax. Results IFN-beta or ATRA inhibited the proliferation and induced the apoptosis of HepG2 cells. The effect was enhanced when IFN-beta was combined with ATRA. The expressions of p-JAK2 and p-STAT3 were down-regulated while the expressions of GRIM-19 and Bax were up regulated after treated with IFN-beta or ATRA on HepG2 cells, especially the combination of IFN-beta and ATRA. Conclusion Combination of IFN-beta and ATRA could suppress the proliferation and induced the apoptosis of HepG2 hepatocarcinoma cells by inhibiting JAK2/STAT3 signal pathway. PMID- 27363270 TI - [Lycium barbarum polysaccharides enhances SIRT1 expression and decreases MMP-9 and HIF-1alpha expressions in hypoxic pulmonary vascular smooth muscle cells]. AB - Objective To investigate the expressions of silent mating type information regulation 2 homolog-1 (SIRT1), matrix metalloproteinase-9 (MMP-9) and hypoxia inducible factor 1alpha (HIF-1alpha) in hypoxic pulmonary vascular smooth muscle cells (PVSMCs) treated with Lycium barbarum polysaccharides (LBP). Methods PVSMCs were divided into 10 groups: normal oxygen (200 mL/L oxygen) cells, 2 MUmol/mL LBP-treated normal oxygen cells, DMSO-treated normal oxygen cells, DMSO-treated hypoxic (100 mL/L oxygen) cells, (0.5, 1, 2) MUmol/mL LBP-treated hypoxic cells; SIRT1 agonist (resveratrol or SRT-1720)-treated hypoxic cells, SIRT1 inhibitor EX 527-treated hypoxic cells. After 6, 12, 24 hours, the mRNA and protein expressions of SIRT1, MMP-9 and HIF-1alpha were measured by real-time quantitative PCR and Western blotting, respectively. In LBP-treated groups, the expressions of SIRT1, MMP-9 and HIF-1alpha mRNA and protein were detected 12 hours after LBP treatment. Results Under the condition of hypoxia, the expression levels of SIRT1 mRNA and protein in PVSMCs decreased, while MMP-9 and HIF-1alpha mRNA increased. Under hypoxia, SIRT1 expression was raised and MMP-9, HIF-1alpha were reduced by LBP treatment in a dose-dependent manner. Morever, resveratrol could inhibit the expression of MMP-9. Conclusion LBP can enhance the expression of SIRT1 and decrease the expression of MMP-9 and HIF-1alpha in hypoxic PVSMCs. PMID- 27363271 TI - [Pulsed electric fields inhibit tumor growth but induce myocardial injury of melanoma-bearing mice]. AB - Objective To investigate the tumor inhibiting effect of pulsed electric fields (PEFs) on melanoma-bearing mice, and understand its influence on myocardial cells and cardial electrical activity. Methods The melanoma models of the BALB/c mice were established by subcutaneously injecting B16 melanoma cells. These mice were randomly divided into four groups. The treated groups received pulsed electric stimulation at pulse width of 1, 3, 5 ms, with field strength of 100 V/cm and frequency of 10 Hz for 10 minutes daily in 15 consecutive days. ECG of mice was recorded. Tumor volume was measured with vernier caliper. Morphological changes of tumors were observed by HE staining. The expression of proliferating cell nuclear antigen (PCNA) mRNA was tested by real-time quantitative PCR, and the expression of PCNA protein was detected by immunofluorescence histochemistry. The ultrastructural changes of the cardiac tissues were observed by transmission electron microscopy (TEM). The serum levels of cardial troponin T (cTnT) and creatine kinase isoenzyme MB (CK-MB) were detected by ELISA. Results Compared with the control group, tumor volumes in all treated groups were reduced 7 days after PEFs treatment; more melanin granules in tumor cells were found in the treated groups; the expressions of PCNA mRNA and protein were down-regulated in all treated groups, and there were greater changes in the groups receiving the bigger pulse width. Myocardial injury was found in 3 ms group and 5 ms group, and the expressions of cTnT and CK-MB were significantly higher than those in the control group. Conclusion PEFs can inhibit tumor growth in melanoma-bearing mice. Increase of pulse width will aggravate myocardial injury. PMID- 27363272 TI - [Irbesartan reduces inflammatory response of central nervous system in a rat model of fluid percussion brain injury]. AB - Objective To investigate the neuroprotective effect of the angiotensin II receptor 1 (AT1) antagonist irbesartan on rat models with lateral fluid percussion brain injury (FPBI). Methods FPBI models were prepared using a modified fluid percussion injury method. Before and after modeling, irbesartan was given to the rats. The regional cerebral blood flow (rCBF) was monitored by laser Doppler flowmetry. Neurologic status was evaluated before and 1, 3, 5, 7 days after FPBI surgery. Brains were removed for immunohistochemical evaluation of active microglias and macrophages. Results Compared to sham group, the rCBF and neurologic score of FPBI rats decreased significantly, while microglia and macrophage activation were confirmed. Treatment with irbesartan before FPBI surgery increased rCBF and improved neurological functions. In the peri-infarct cortex, irbesartan treatment attenuated the invasion of activated microglias and macrophages on day 7 after FPBI surgery. Conclusion Irbesartan can play a neuroprotective role through inhibiting microglia and macrophage activation in FPBI rats. PMID- 27363273 TI - [Emodin inhibits the proliferation, transdifferentiation and collagen synthesis of pulmonary fibroblasts]. AB - Objective To explore the effect of emodin on the proliferation, differentiation into myofibroblasts and collagen synthesis of pulmonary fibroblasts and the underlying mechanisms. Methods Human pulmonary fibroblasts MRC-5 were cultured in vitro, then the cells were inoculated with dimethyl sulfoxide (DMSO) added with 0, 10, 20, 40, 80 and 160 MUmol/L emodin for 24, 48 and 72 hours. Inhibitory rate of cell proliferation was analyzed by MTT assay. Based on the results of cell proliferation experiment, MRC-5 cells were treated with DMSO (control group) and 40, 80 MUmol/L emodin (in DMSO) for 48 hours. Fluorescence real-time quantitative PCR was then used to measure the mRNA expressions of alpha-smooth muscle actin (alpha-SMA), transforming growth factor-beta1 (TGF-beta1), a disintegrin-like and metalloproteinase with thrombospondin type 1 motif (ADAMTS-1), collagen type 1 (Col1) and collagen type 3 (Col3). The protein expressions of the above mentioned factors were also measured by Western blotting. Results In a concentration- and time-dependent manner, emodin inhibited MRC-5 cell proliferation. After 48 hours of co-culture, in comparison with control group, the mRNA and protein expression levels of alpha-SMA, TGF-beta1, Col1 and Col3 significantly decreased, while the mRNA and protein expression levels of ADAMTS-1 significantly increased in 40 and 80 MUmol/L emodin-treated groups. Moreover, in comparison with 40 MUmol/L emodin treated group, the mRNA and protein expressions of alpha-SMA, TGF-beta1, Col1 and Col3 were significantly downregulated, but ADAMTS-1 mRNA and protein expressions were significantly upregulated in 80 MUmol/L emodin-treated group. Conclusion Emodin can block pulmonary fibroblast proliferation and differentiation into myofibroblasts, and reduce the synthesis of Col1 and Col3 by inhibiting TGF beta1/ADAMTS-1 signaling pathway. PMID- 27363274 TI - [Insulin combined with selenium inhibit p38MAPK/CBP pathway and suppresses cardiomyocyte apoptosis in rats with diabetic cardiomyopathy]. AB - Objective To investigate the effect of insulin in combination with selenium on p38-mitogen-activated protein kinase/CREB-binding protein (p38MAPK/CBP) pathway in rats with diabetic cardiomyopathy. Methods Fifty SD rats were randomly grouped into control group, diabetic cardiomyopathy (DCM) group, diabetic cardiomyopathy with insulin treatment (DCM-In) group, diabetic cardiomyopathy with selenium treatment (DCM-Se) group, and diabetic cardiomyopathy with insulin and selenium combination treatment (DCM-In-Se) group. Flow cytometry was used to analyze cell cycle. TUNEL staining was used to detect cardiomyocyte apoptosis. Western blotting was used to examine the levels of cyclin D1, cyclin E, Bax, Bcl-2, p38MAPK, p-p38MAPK, CBP and Ku70. Co-immunoprecipitation was used to examine the acetylation status of Ku70. Results Insulin in combination with selenium significantly inhibited cardiomyocyte apoptosis, increased Bcl-2 levels and decreased Bax, cyclin D1, cyclin E, p38MAPK, p-p38MAPK, CBP, Ku70 and acetylated Ku70 levels. Conclusion The combined treatment of insulin and selenium suppresses cardiomyocyte apoptosis by inhibiting p38MAPK/CBP pathway. PMID- 27363276 TI - [Phosphatidylinositide 3-kinase inhibitor BKM120 suppresses proliferation and promotes apoptosis of U251 glioblastoma cells]. AB - Objective To investigate the effect of phosphatidylinositide 3-kinase (PI3K) inhibitor BKM120 on the proliferation and apoptosis of human glioma U251 cells. Methods U251 cells were treated with different concentrations of BKM120 (final concentrations were 1, 5, 20 MUmol/L) for 48 hours. The effect of BKM120 on cell proliferation was detected by CCK-8 assay. The apoptosis was detected by annexin V-FITC/PI staining. The protein expressions of Bax and Bcl-2 were detected by Western blotting. Results CCK-8 assay showed that BKM120 inhibited U251 proliferation in a concentration-dependent manner and the maximum inhibitory rate was 78.3%. Flow cytometry showed that BKM120 induced cell aopotosis in a concentration-dependent manner. Western blotting revealed that the expression of Bax was elevated by BKM120, but the expression of Bcl-2 had a reverse trend. Conclusion BKM120 can inhibit the proliferation and induce the apoptosis of U251 cells. PMID- 27363275 TI - [Down-regulation of p38 MAPK and collagen by 1, 25-(OH)2-VD3 in rat models of diabetic nephropathy]. AB - Objective To investigate the effect of 1, 25-(OH)2-VD3 on collagen type III (Col3), collagen type IV (Col4) and p38 mitogen-activated protein kinase (p38 MAPK) in rat models of type 2 diabetic nephropathy, and explore the relationships of p38MAPK with Col3 and Col4. Methods Rat models of type 2 diabetic nephropathy were induced by streptozocin (STZ, 30 mg/kg) combined with high-glucose-and-fat diet. Sixty rats were randomly divided into control group, model group, 1, 25 (OH)2-VD3 treatment group [given 1, 25-(OH)2-VD3 6 ng/(100 g.d) after modeling] and insulin group (given 2-3 U insulin after modeling). After 8 weeks' intervention, serum creatinine (Scr), blood urea nitrogen (BUN) and 24-hour proteinuria were detected in all groups. Periodic acid-Schiff (PAS) staining was used to observe the kidney pathological changes, and immunohistochemical staining and Western blotting were performed to determine p38 MAPK Col3 and Col4 expressions in rat renal interstitium. Spearman method was applied to the correlation analysis. Results Compared with the model group, blood glucose, Scr, BUN, 24-hour proteinuria and impaired renal interstitial area were all reduced in the 1, 25-(OH)2-VD3 treatment group and the insulin group. Compared with the control group, the expressions of Col3, Col4 and p38 MAPK were higher in the model group, and lower in the 1, 25-(OH)2-VD3 treatment group and the insulin group. Correlation analysis showed that 24-hour proteinuria was positively related with p38 MAPK, Col3, Col4 and immunohistochemical results; p38MAPK was positively correlated with Col3 and Col4 expressions. Conclusion Col3, Col4 and p38MAPK are up-regulated in rat models of type 2 diabetic nephropathy. The 1, 25 (OH)2-VD3 might attenuates the progression of renal interstitial fibrosis via down-regulating p38 MAPK, Col3 and Col4. PMID- 27363277 TI - [Evodiamine enhances the radiosensitivity of esophageal squamous cell cancer Eca 109 cells]. AB - Objective To investigate the effect of evodiamine on the radiosensitivity of esophageal squamous cell cancer Eca-109 cells. Methods Eca-109 cells were treated with various concentrations of evodiamine [(10, 20, 40, 60, 80, 100, 120) MUg/mL], and then cell proliferation was examined by MTT assay. After the optimal evodiamine concentration was determined, the cells were divided into radiation group (0, 2, 4, 6, 8 Gy X-ray radiation) and radiation combined with evodiamine group (80 MUg/mL evodiamine and 0, 2, 4, 6, 8 Gy X-ray radiation) .The radiosensitivity of Eca-109 cells was detected using colony formation assay. Flow cytometry was used to determine cell cycle of Eca-109 cells. The protein expressions of Ku70, Ku80, DNA-PKcs and Rad51 were examined by Western blotting. Results MTT assay showed that evodiamine decreased the proliferation of Eca-109 cells in a concentration-dependent manner. The inhibition reached the maximal level at 80 MUg/mL. Compared with radiotherapy alone, the combination of 80 MUg/mL evodiamine and radiotherapy improved survival curve and decreased the values of D0 and Dq. Sensitizer enhancement ratio was 1.86+/-0.06. Furthermore, cell cycle analysis revealed that evodiamine suppressed radiotherapy-induced the G2/M arrest. Additionally, evodiamine treatment also significantly inhibited radiotherapy-induced increase in Ku70, Ku80, DNA-PKcs and Rad51 expressions. Conclusion Evodiamine enhances radiosensitivity of Eca-109 cells during radiotherapy. The effect may be associated with the inhibition of G2/M arrest and the attenuation of Ku70, Ku80, DNA-PKcs and Rad51 expressions. PMID- 27363278 TI - [Overexpression of miR-125b promotes apoptosis of macrophages]. AB - Objective To investigate the expressions of miR-125b and target gene Raf1 proto oncogene serine/threonine protein kinase (RAF1) in peripheral blood mononuclear cells (PBMCs) of pediatric patients with pulmonary tuberculosis (PTB), and observe the regulation of miR-125b on macrophage apoptosis and activity. Methods PBMCs of patients with PTB and healthy children were collected and separated. Real-time fluorescence quantitative PCR was used to detect mRNA expression level of miR-125b and RAF1, and Western blotting was used to detect the protein level of RAF1. THP-1 macrophages were transfected into miR-125b mimic, negative control mimic (NC-mimic), miR-125b inhibitor and negative control inhibitor (NC inhibitor), which were cultured for 48 hours. Western blotting was performed to observe the expression of RAF1 in THP-1 macrophages, annexin V-FITC/PI double staining combined with flow cytometry was used to test cell apoptosis, and CCK-8 assay was used to detect cell proliferation. Results The expression of miR-125b in PBMCs in pediatric patients with PTB was downregulated, and mRNA and protein levels of RAF1 were upregulated. When miR-125b was over-expressed in THP-1 macrophages, the expression of RAF1 was reduced to promote the apoptosis of macrophages and decrease cell activity; when the expression of miR-125b was inhibited in THP-1 macrophages, the expression of RAF1 was elevatedand the apoptosis of macrophages was inhibited, the cell activity was promoted. Conclusion In PBMCs of children with PTB, miR-125b level is low. Upregulation of miR-125b in THP-1 macrophages, the apoptosis of THP-1 macrophages is promoted and cell activity is inhibited. PMID- 27363279 TI - [Increased expressions of Blimp-1 and Bcl-6 in the deciduas of patients with unexplained recurrent spontaneous abortion]. AB - Objective To oberseve the expressions of B cell lymphoma 6 (Bcl-6) and B lymphocyte-induced maturation protein 1 (Blimp-1) in the decidua of patients with unexplained recurrent spontaneous abortion (URSA), and investigate the roles that Bcl-6 and Blimp-1 act in URSA. Methods Decidual tissues were collected from patients with URSA (URSA group) and normal pregnant women (control group). Then, we detected the expressions of Bcl-6 and Blimp-1 in the deciduas of the two groups using real-time fluorescent quantitative PCR and immunohistochemistry. The relationship between Blimp-1 and Bcl-6 was estimated by Pearson's correlation analysis. Results Compared with the control group, the levels of Blimp-1 mRNA and protein, Bcl-6 mRNA significantly increased in the URSA group. However, Bcl-6 protein was raised insignificantly in URSA group. Furthermore, there was a positive correlation between Bcl-6 and Blimp-1 at the level of mRNA. Conclusion The expressions of Bcl-6 and Blimp-1 are enhanced in the deciduas of URSA patients. PMID- 27363280 TI - [Increased serum levels of soluble T cell immunoglobulin mucin molecule 3 and IL 4 and decreased IFN-gamma in patients with pulmonary tuberculosis]. AB - Objective To detect the serum levels of soluble T cell immunoglobulin mucin molecule 3 (sTim-3), IFN-gamma and IL-4 in patients with pulmonary tuberculosis. Methods Peripheral blood was collected from 48 patients with pulmonary tuberculosis and 20 healthy controls. The serum level of sTim-3 was detected by ELISA. The levels of IFN-gamma and IL-4 were determined by cytokine bead array (CBA). The correlations between sTim-3, IFN-gamma and IL-4 levels in sera of patients with pulmonary tuberculosis were analyzed by Pearson correlation test. Results Compared with the control group, the serum levels of sTim-3 and IL-4 increased significantly, while the level of IFN-gamma decreased significantly. Pearson analysis showed that there was a negative correlation between sTim-3 and IFN-gamma as well as between IFN-gamma and IL-4 in patients with pulmonary tuberculosis, while sTim-3 and IL-4 were positively correlated. Conclusion The serum levels of sTim-3 and IL-4 increase, but IFN-gamma decreases in the patients with pulmonary tuberculosis. PMID- 27363281 TI - Synergistic Effects of Self-Doped Nanostructures as Charge Trapping Elements in Organic Field Effect Transistor Memory. AB - Despite remarkable advances in the development of organic field-effect transistor (OFET) memories over recent years, the charge trapping elements remain confined to the critical electrets of polymers, nanoparticles, or ferroelectrics. Nevertheless, rare reports are available on the complementary advantages of different types of trapping elements integrated in one single OFET memory. To address this issue, we fabricated two kinds of pentacene-based OFET memories with solution-processed amorphous and beta-phase poly(9,9-dioctylfluorene) (PFO) films as charge trapping layers, respectively. Compared to the amorphous film, the beta PFO film has self-doped nanostructures (20-120 nm) and could act as natural charge trapping elements, demonstrating the synergistic effects of combining both merits of polymer and nanoparticles into one electret. Consequently, the OFET memory with beta-PFO showed nearly 26% increment in the storage capacity and a pronounced memory window of ~45 V in 20 ms programming time. Besides, the retention time of beta-PFO device extended 2 times to maintain an ON/OFF current ratio of 10(3), indicating high bias-stress reliability. Furthermore, the beta PFO device demonstrated good photosensitivity in the 430-700 nm range, which was attributed to the additive effect of smaller bandgap and self-doped nanostructures of beta-phase. In this regard, the tuning of molecular conformation and aggregation in a polymer electret is an effective strategy to obtain a high performance OFET memory. PMID- 27363282 TI - MicroRNA-155 induces AML in combination with the loss of C/EBPA in mice. PMID- 27363284 TI - Experiences of Korean adolescent renal transplant recipients. AB - PURPOSE: To understand the experiences of Korean adolescents who have undergone a renal transplant. DESIGN AND METHODS: Nine adolescents aged 12-18 who received a renal transplant participated in this qualitative descriptive study. Using content analysis, we analyzed in-depth interview data from individual adolescents. RESULTS: The main themes extracted were "being different from others," "not being invited as a decision maker," "becoming one of them," "still being different from others," "having mixed feeling toward mothers," and "coping with new circumstances." PRACTICE IMPLICATIONS: Interventions designed to improve adolescent renal transplant recipients' sense of autonomy and belongingness are needed. PMID- 27363283 TI - Patient-derived xenotransplants can recapitulate the genetic driver landscape of acute leukemias. AB - Genomic studies have identified recurrent somatic mutations in acute leukemias. However, current murine models do not sufficiently encompass the genomic complexity of human leukemias. To develop preclinical models, we transplanted 160 samples from patients with acute leukemia (acute myeloid leukemia, mixed lineage leukemia, B-cell acute lymphoblastic leukemia, T-cell ALL) into immunodeficient mice. Of these, 119 engrafted with expected immunophenotype. Targeted sequencing of 374 genes and 265 frequently rearranged RNAs detected recurrent and novel genetic lesions in 48 paired primary tumor (PT) and patient-derived xenotransplant (PDX) samples. Overall, the frequencies of 274 somatic variant alleles correlated between PT and PDX samples, although the data were highly variable for variant alleles present at 0-10%. Seventeen percent of variant alleles were detected in either PT or PDX samples only. Based on variant allele frequency changes, 24 PT-PDX pairs were classified as concordant while the other 24 pairs showed various degree of clonal discordance. There was no correlation of clonal concordance with clinical parameters of diseases. Significantly more bone marrow samples than peripheral blood samples engrafted discordantly. These data demonstrate the utility of developing PDX banks for modeling human leukemia, and emphasize the importance of genomic profiling of PDX and patient samples to ensure concordance before performing mechanistic or therapeutic studies. PMID- 27363285 TI - Further evidence that prevention of maternal vitamin D deficiency may benefit the health of the next generation. PMID- 27363287 TI - Design and Synthesis of Aviram-Ratner-Type Dyads and Rectification Studies in Langmuir-Blodgett (LB) Films. AB - The design and synthesis of Aviram-Ratner-type molecular rectifiers, featuring an anilino-substituted extended tetracyanoquinodimethane (exTCNQ) acceptor, covalently linked by the sigma-spacer bicyclo[2.2.2]octane (BCO) to a tetrathiafulvalene (TTF) donor moiety, are described. The rigid BCO spacer keeps the TTF donor and exTCNQ acceptor moieties apart, as demonstrated by X-ray analysis. The photophysical properties of the TTF-BCO-exTCNQ dyads were investigated by UV/Vis and EPR spectroscopy, electrochemical studies, and theoretical calculations. Langmuir-Blodgett films were prepared and used in the fabrication and electrical studies of junction devices. One dyad showed the asymmetric current-voltage (I-V) curve characteristic for rectification, unlike control compounds containing the TTF unit but not the exTCNQ moiety or comprising the exTCNQ acceptor moiety but lacking the donor TTF part, which both gave symmetric I-V curves. The direction of the observed rectification indicated that the preferred electron current flows from the exTCNQ acceptor to the TTF donor. PMID- 27363286 TI - Major influence of CD4 count at the initiation of cART on viral and immunological reservoir constitution in HIV-1 infected patients. AB - BACKGROUND: A persistent immune activation is observed in gut during HIV-1 infection, which is not completely reversed by a combined antiretroviral therapy (cART). The impact of the time of cART initiation may highly influence the size of the viral reservoir and the ratio of CD4(+)/CD8(+) T cells in the gut. In this study, we analyzed the characteristics of HIV rectal reservoir of long-term treated patients, regarding their blood CD4(+) T cells count at the time of cART initiation. RESULTS: Twenty-four consenting men were enrolled: 9 exhibiting a CD4(+) T cells count >350/mm(3) ("high-level CD4 group") and 15 < 350/mm(3) ("low level CD4 group") in blood, at the start of cART. An immunophenotypical analysis of T and B cells subpopulations was performed in blood and rectal biopsies. HIV cell-associated DNA loads and qualitative intra-cellular RNA were determined in both compartments. The ratio of CD4(+)/CD8(+) T cells was significantly decreased in the blood but not in the rectum of the "low-level CD4 group" of patients. The alteration in beta7(+) CD4(+) T cells homing was higher in this group and was correlated to a low ratio of CD4(+)/CD8(+) T cells in blood. An initiation of cART in men exhibiting a low-level CD4 count was also associated with an alteration of B cells maturation. HIV blood and gut DNA reservoirs were significantly lower in the "high-level CD4 group" of men. A high HIV DNA level was associated to a detectable intracellular HIV RNA in rectum. CONCLUSIONS: An early initiation of cART could significantly preserve gut immunity and limit the viral reservoir constitution. PMID- 27363289 TI - Accelerating effects of cellulase in the removal of denture adhesives from acrylic denture bases. AB - PURPOSE: Studies of effective methods for the easy removal of denture adhesives from a denture base are not well represented in the literature. We previously assessed the removability of denture adhesives by immersing within denture cleaners, showing that some cleaners have a weak effect, insufficiently effective in daily use. In this study, we prepared a cellulase, as a potential component for denture adhesive removers, and we examined whether the addition of cellulase to denture cleaners is effective in the removal of cream denture adhesives. METHODS: We prepared the cellulase Meicelase as one component for the liquefaction of denture adhesives. We used two denture cleaners and two cream adhesives. After the immersion of plates in sample solutions, we evaluated the area of the sample plate still covered with adhesives. Biofilm removal assay was also performed using denture cleaners containing cellulase. RESULTS: The addition of cellulase accelerated the removal of cream adhesives in immersion experiments to a rate faster than that of water and denture cleaners. However, it did not influence the removability of Candida albicans biofilms from acrylic resin specimens. CONCLUSION: Cellulase hastened the liquefaction of cream adhesives. PMID- 27363288 TI - Ethnic differences in incidence of hepatitis B surface antigen seroclearance in a real-life multicenter clinical cohort of 4737 patients with chronic hepatitis B infection. AB - BACKGROUND: Hepatitis B surface antigen (HBsAg) positivity is associated with increased risk for cirrhosis and hepatocellular carcinoma (HCC). HBsAg seroclearance is thought to be rare in general, but cohort data from US patients are limited. AIM: To determine the incidence of HBsAg seroclearance in a real life US cohort. METHODS: In total, 4737 patients with chronic hepatitis B from five primary care, gastroenterology and multispecialty centres, and a university medical centre were retrospectively enrolled between 2001 and 2014 with data obtained by manual review of individual patient medical records. Seroclearance was determined by loss of HBsAg seropositivity. Persistent HBsAg was confirmed by direct serology or by proxy with positive hepatitis B e-antigen (HBeAg) or HBV DNA levels. RESULTS: HBsAg seroclearance occurred in 52 patients over 16 844 person-years (0.31% annually, 1.2% overall). Median follow-up was 32 months, and mean age 45 +/- 14 years. Incidence of HBsAg seroclearance was higher in non Asians, age >45, males, and those with baseline HBV DNA <=10 000 IU/mL. On multivariate Cox proportional modelling, non-Asian ethnicity (HR 2.8), male sex (HR 2.1), baseline HBVDNA <=10 000 (HR 2.0) and age >45 (HR 1.8) were significant independent predictors of seroclearance. CONCLUSION: HBsAg seroclearance rates were lower than previously described in this real-life cohort of patients with chronic hepatitis B, especially among Asian, female and younger patients. PMID- 27363290 TI - InGaN Light-Emitting Diodes with an Embedded Nanoporous GaN Distributed Bragg Reflectors. AB - InGaN light emitting diodes (LED) structure with an embedded 1/4lambda-stack nanoporous-GaN/undoped-GaN distributed Bragg reflectors (DBR) structure have been demonstrated. Si-heavily doped GaN epitaxial layers (n(+)-GaN) in the 12-period n(+)-GaN/u-GaN stack structure are transformed into low refractive index nanoporous GaN structure through the doping-selective electrochemical wet etching process. The central wavelength of the nanoporous DBR structure was located at 442.3 nm with a 57 nm linewidth and a 97.1% peak reflectivity. The effective cavity length (6.0lambda), the effective penetration depth (278 nm) in the nanoporous DBR structure, and InGaN active layer matching to Fabry-Perot mode order 12 were observed in the far-field photoluminescence radiative spectra. High electroluminescence emission intensity and line-width narrowing effect were measured in the DBR-LED compared with the non-treated LED structure. Non-linear emission intensity and line-width reducing effect, from 11.8 nm to 0.73 nm, were observed by increasing the laser excited power. Resonant cavity effect was observed in the InGaN LED with bottom nanoporous-DBR and top GaN/air interface. PMID- 27363291 TI - Pharmacologic Treatment of Rett Syndrome With Glatiramer Acetate. AB - BACKGROUND: Rett syndrome (RTT) is a severe neurological disease that primarily affects females. The level of brain derived neurotropic factor (BDNF) expression directly correlates with the severity of RTT related symptoms. Because Glatiramer acetate (GA) stimulates secretion of BDNF in the brain, we conducted the study with the objective to assess its efficacy in improving gait velocity cognition, respiratory function, electroencephalographic findings, and quality of life in patients with RTT. METHODS: Phase two, open label, single center trial. INCLUSION CRITERIA: ambulatory girls with genetically confirmed RTT, 10 years or older. Pre and post-treatment measures were compared using the non-parametric Wilcoxon signed rank sum test and paired t-tests. RESULTS: Ten patients were enrolled and completed the trial. Gait velocity improved significantly (improvement range 13% 95%, p=0.03 for both tests) and emerged as an especially valuable outcome measure with excellent test- retest reliability of the 2 trials within sessions (intraclass correlation coefficient=0.94). Memory, and the breath holding index also improved significantly (p<=0.03). Epileptiform discharges decreased in all four patients who had them at baseline. There was a trend towards improved quality of life, which did not reach statistical significance. CONCLUSIONS: This prospective open-label trial provides important preliminary information related to the efficacy of GA in improving gait velocity in female patients with RTT who are 10 years or older. The results of this trial justify the need for larger scale controlled trials of GA as well as provide a template for assessing the efficacy of other interventions in RTT. PMID- 27363292 TI - Recognizing Primary Myoclonus Dystonia. PMID- 27363293 TI - Syntactic Change in the Parallel Architecture: The Case of Parasitic Gaps. AB - In Jackendoff's Parallel Architecture, the well-formed expressions of a language are licensed by correspondences between phonology, syntax, and conceptual structure. I show how this architecture can be used to make sense of the existence of parasitic gap constructions. A parasitic gap is one that is rendered acceptable because of the presence of another gap in the same sentence. Compare *a person whoi everyone who talks to ti likes Chris, which shows an illicit extraction from a relative clause, and a person whoi everyone who talks to pgi likes ti, which shows a parasitic gap in the relative clause. Languages differ in terms of the range of configurations in which they allow parasitic gaps; these configurations appear to form a hierarchy. These observations raise some fundamental questions: Why do parasitic gaps exist at all? Why are different syntactic configurations possible for P-gaps and why just these configurations? Why is there a parasitic gap hierarchy? The answers that I propose make crucial use of constructional overgeneralization of across-the-board extraction in coordinate constructions, formulated straightforwardly in the framework of Jackendoff's Parallel Architecture. PMID- 27363296 TI - Percutaneous Treatment of Herniated Lumbar Discs with Ozone: Investigation of the Mechanisms of Action. AB - PURPOSE: To elucidate the mechanism of action of intradiscal oxygen-ozone therapy for herniated intervertebral disc therapy. METHODS: Ozone's mechanism of action was investigated using 3 approaches: mathematical models of intervertebral disc space to explore the relationship between disc pressure and volume; ozonolysis experiments using glycosaminoglycans (GAGs) from a Chinese hamster ovary cell line that were similar in composition to GAGs found in human nucleus pulposus; and experiments in which live Yucatan miniature pigs received various concentrations of percutaneous, image-guided intradiscal oxygen-ozone treatment and were examined (after sacrifice) with histology and semiquantitative analysis of disc cytokine concentrations. RESULTS: Engineering calculations support observations that a small (6%) disc volume reduction can result in considerable (9.84%) intradiscal pressure reduction. Porcine disc histology and Chinese hamster ovary GAG ozonolysis results showed that administered ozone reacted with and fragmented disc proteoglycans, reducing disc volume through disc dehydration. Cytokine analysis of porcine discs found that each of 4 cytokines measured (interleukin [IL]-1beta, IL-6, IL-8, and tumor necrosis factor alpha) increased in concentration after 2 wt% ozone treatment. CONCLUSIONS: Oxygen-ozone therapy breaks down proteoglycan GAGs that maintain disc osmotic pressure, dehydrating the nucleus pulposus and reducing intervertebral disc volume. This is likely a primary mechanism by which ozone relieves nerve root compression and alleviates herniated disc-related pain. Additionally, 2 wt% ozone appears to interact with intradiscal cytokines, generating an antiinflammatory response that may contribute to symptom improvement. PMID- 27363297 TI - Understanding Preprocedure Patient Flow in IR. AB - PURPOSE: To quantify preprocedural patient flow in interventional radiology (IR) and to identify potential contributors to preprocedural delays. MATERIALS AND METHODS: An administrative dataset was used to compute time intervals required for various preprocedural patient-flow processes. These time intervals were compared across on-time/delayed cases and inpatient/outpatient cases by Mann Whitney U test. Spearman rho was used to assess any correlation of the rank of a procedure on a given day and the procedure duration to the preprocedure time. A linear-regression model of preprocedure time was used to further explore potential contributing factors. Any identified reason(s) for delay were collated. P < .05 was considered statistically significant. RESULTS: Of the total 1,091 cases, 65.8% (n = 718) were delayed. Significantly more outpatient cases started late compared with inpatient cases (81.4% vs 45.0%; P < .001, chi(2) test). The multivariate linear regression model showed outpatient status, length of delay in arrival, and longer procedure times to be significantly associated with longer preprocedure times. Late arrival of patients (65.9%), unavailability of physicians (18.4%), and unavailability of procedure room (13.0%) were the three most frequently identified reasons for delay. The delay was multifactorial in 29.6% of cases (n = 213). CONCLUSIONS: Objective measurement of preprocedural IR patient flow demonstrated considerable waste and highlighted high-yield areas of possible improvement. A data-driven approach may aid efficient delivery of IR care. PMID- 27363295 TI - Ca(2+)/calmodulin-activated phosphodiesterase 1A is highly expressed in rabbit cardiac sinoatrial nodal cells and regulates pacemaker function. AB - Constitutive Ca(2+)/calmodulin (CaM)-activation of adenylyl cyclases (ACs) types 1 and 8 in sinoatrial nodal cells (SANC) generates cAMP within lipid-raft-rich microdomains to initiate cAMP-protein kinase A (PKA) signaling, that regulates basal state rhythmic action potential firing of these cells. Mounting evidence in other cell types points to a balance between Ca(2+)-activated counteracting enzymes, ACs and phosphodiesterases (PDEs) within these cells. We hypothesized that the expression and activity of Ca(2+)/CaM-activated PDE Type 1A is higher in SANC than in other cardiac cell types. We found that PDE1A protein expression was 5-fold higher in sinoatrial nodal tissue than in left ventricle, and its mRNA expression was 12-fold greater in the corresponding isolated cells. PDE1 activity (nimodipine-sensitive) accounted for 39% of the total PDE activity in SANC lysates, compared to only 4% in left ventricular cardiomyocytes (LVC). Additionally, total PDE activity in SANC lysates was lowest (10%) in lipid-raft rich and highest (76%) in lipid-raft-poor fractions (equilibrium sedimentation on a sucrose density gradient). In intact cells PDE1A immunolabeling was not localized to the cell surface membrane (structured illumination microscopy imaging), but located approximately within about 150nm inside of immunolabeling of hyperpolarization-activated cyclic nucleotide-gated potassium channels (HCN4), which reside within lipid-raft-rich microenvironments. In permeabilized SANC, in which surface membrane ion channels are not functional, nimodipine increased spontaneous SR Ca(2+) cycling. PDE1A mRNA silencing in HL-1 cells increased the spontaneous beating rate, reduced the cAMP, and increased cGMP levels in response to IBMX, a broad spectrum PDE inhibitor (detected via fluorescence resonance energy transfer microscopy). We conclude that signaling via cAMP generated by Ca(2+)/CaM-activated AC in SANC lipid raft domains is limited by cAMP degradation by Ca(2+)/CaM-activated PDE1A in non-lipid raft domains. This suggests that local gradients of [Ca(2+)]-CaM or different AC and PDE1A affinity regulate both cAMP production and its degradation, and this balance determines the intensity of Ca(2+)-AC-cAMP-PKA signaling that drives SANC pacemaker function. PMID- 27363298 TI - Utility of Intravascular US-Guided Portal Vein Access during Transjugular Intrahepatic Portosystemic Shunt Creation: Retrospective Comparison with Conventional Technique in 109 Patients. AB - PURPOSE: To compare safety and effectiveness of intravascular ultrasound (US) guided portal vein access during transjugular intrahepatic portosystemic shunt (TIPS) creation with conventional TIPS technique. MATERIALS AND METHODS: In this retrospective study, TIPS creation using intravascular US guidance in 55 patients was compared with conventional TIPS creation in 54 patients by 10 operators over a 3-year period. Operators were classified as experienced if they had performed >= 20 TIPS procedures at the beginning of the study period. Time to portal vein access, total radiation dose, and needle pass-related capsular perforation were recorded. RESULTS: Baseline demographic characteristics of patients were similar (P > .05). Mean time to portal venous access was 46 minutes +/- 37 for conventional TIPS and 31 minutes +/- 19 for intravascular US-guided TIPS (P = .007). Intravascular US guidance allowed significantly shorter times (48 min +/- 30 vs 28 min +/- 16; P = .01) to portal vein access among operators (n = 5) with limited experience but failed to achieve any significant time savings (44 min +/- 43 vs 34 min +/- 22; P = .89) among experienced operators (n = 5). Needle pass related capsular perforation occurred in 17/54 (34%) patients with conventional TIPS and 5/55 (9%) patients with intravascular US-guided TIPS (P = .004). Radiation dose was 2,376 mGy +/- 1,816 for conventional TIPS and 1,592 mGy +/- 1,263 for intravascular US-guided TIPS (P = .004). CONCLUSIONS: Intravascular US guided portal vein access during TIPS creation is associated with shorter portal vein access times, decreased needle pass-related capsular perforations, and reduced radiation dose. PMID- 27363299 TI - Catheter-Directed Intraarterial Thrombolysis as Part of a Multidisciplinary Management Protocol of Frostbite Injury. AB - PURPOSE: To evaluate intraarterial catheter-directed thrombolysis for prediction and prevention of delayed surgical amputation as part of multidisciplinary management of frostbite injury. MATERIALS AND METHODS: A retrospective review was performed of 13 patients (11 men, 2 women; median age, 33.4 y; range, 8-62 y) at risk of tissue loss secondary to frostbite injury and treated with catheter directed tissue plasminogen activator (t-PA) thrombolysis. Amputation data were assessed on follow-up (mean, 23 mo; range, 9-83 mo). Angiographic findings were classified into complete, partial, and no angiographic response and assessed for association with follow-up amputation rates. Correlation between amputation outcome and duration of cold exposure (mean, 23 h; range, 5-96 h), time between exposure and rewarming therapy (mean, 25.5 h; range, 7-95 h), and time between exposure and t-PA thrombolysis (mean, 32 h; range, 12-96 h) was assessed. Complications were recorded. RESULTS: Of 127 digits at risk on baseline angiography that were treated with catheter-directed thrombolysis, complete recovery was seen in 106 (83.4%). Total mean t-PA dose per extremity was 27.5 mg (range, 12-48 mg) over a mean period of 34 hours (range, 12-72 h). Patients with complete angiographic response (8 patients; 79.5% of digits) did not require amputations; 4 of 5 patients (80%) with partial angiographic response (20.5% of digits) underwent amputation (P = .007). There was no significant correlation between amputation rates and duration of cold exposure (P = .9), time to rewarming therapy (P = .88), and time to thrombolysis (P = .56). Femoral access site bleeding in 2 patients was managed conservatively. One patient underwent surgical exploration for brachial artery hematoma. CONCLUSIONS: Intraarterial catheter-directed thrombolysis should be included in initial management of frostbite injury, as it may prevent delayed amputations. The degree of angiographic response to thrombolysis can potentially predict amputation outcomes. PMID- 27363300 TI - Perovskite SrCo0.9 Nb0.1 O3-delta as an Anion-Intercalated Electrode Material for Supercapacitors with Ultrahigh Volumetric Energy Density. AB - We have synthesized and characterized perovskite-type SrCo0.9 Nb0.1 O3-delta (SCN) as a novel anion-intercalated electrode material for supercapacitors in an aqueous KOH electrolyte, demonstrating a very high volumetric capacitance of about 2034.6 F cm(-3) (and gravimetric capacitance of ca. 773.6 F g(-1) ) at a current density of 0.5 A g(-1) while maintaining excellent cycling stability with a capacity retention of 95.7 % after 3000 cycles. When coupled with an activated carbon (AC) electrode, the SCN/AC asymmetric supercapacitor delivered a specific energy density as high as 37.6 Wh kg(-1) with robust long-term stability. PMID- 27363301 TI - Platinum-catalysed intermolecular addition of carbonyl compounds to 1,6-enynes: investigation of a new reaction pathway. AB - A novel intermolecular addition of aldehydes to 1,6-enynes via a Pt-carbene intermediate provides the diastereoselective formation of valuable tricyclic compounds. PMID- 27363302 TI - ITGAV and ITGA5 diversely regulate proliferation and adipogenic differentiation of human adipose derived stem cells. AB - The fate of human adipose tissue stem cells (ASCs) is largely determined by biochemical and mechanical cues from the extracellular matrix (ECM), which are sensed and transmitted by integrins. It is well known that specific ECM constituents influence ASC proliferation and differentiation. Nevertheless, knowledge on how individual integrins regulate distinct processes is still limited. We performed gene profiling of 18 alpha integrins in sorted ASCs and adipocytes, identifying downregulations of RGD-motif binding integrins integrin alpha-V (ITGAV) and integrin-alpha-5 (ITGA5), upregulation of laminin binding and leukocyte-specific integrins and individual regulations of collagen and LDV receptors in differentiated adipocytes in-vivo. Gene function analyses in in vitro cultured ASCs unraveled differential functions of ITGA5 and ITGAV. Knockdown of ITGAV, but not ITGA5 reduced proliferation, caused p21(Cip1) induction, repression of survivin and specific regulation of Hippo pathway mediator TAZ. Gene knockdown of both integrins promoted adipogenic differentiation, while transgenic expression impaired adipogenesis. Inhibition of ITGAV using cilengitide resulted in a similar phenotype, mimicking loss of pan ITGAV expression using RNAi. Herein we show ASC specific integrin expression patterns and demonstrate distinct regulating roles of both integrins in human ASCs and adipocyte physiology suggesting a negative impact of RDG-motif signaling on adipogenic differentiation of ASCs via ITGA5 and ITGAV. PMID- 27363303 TI - The death of Alaric I (c. 370-410AD), the vanquisher of Rome: Additional arguments strengthening the possible involvement of malaria. PMID- 27363305 TI - Data sharing: When better may be the enemy of good. PMID- 27363304 TI - Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors to treat hypercholesterolemia: Effect on stroke risk. AB - BACKGROUND/PURPOSE: A reduction of cardiovascular events has been reported in phase 2 and 3 trials of the proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors alirocumab and evolocumab. We aimed to investigate the effect PCSK9 inhibition on stroke risk in a meta-analysis involving data from randomized studies with alirocumab and evolocumab. METHODS: Data from pre-specified combined analysis of 4465 patients who completed phase 2 or 3 studies of evolocumab over a period of 1year and a randomized trial on alirocumab including 2341 patients with hyperlipidemia on maximally tolerated statin who were at high risk for coronary heart disease over a period of 1.5years were used. RESULTS: The number of patients having an ischemic stroke was small in both trials. PCSK9 inhibition showed no significant effect on stroke rate (risk ratio 1.43; 95% CI, 0.45-4.57, p=0.55). No significant differences in stroke risk were evident when transient ischemic attacks were included in the analysis (risk ratio 0.65; 95% CI, 0.25 1.68, p=0.37). No hemorrhagic strokes were reported in either study. CONCLUSION: Although a benefit towards reduction of cardiovascular events in the overall has been documented, longer exposure is warranted to be able to evaluate the effect on stroke risk. PMID- 27363306 TI - Declining trends in the incidence of hip fractures in people aged 65years or over in years 2000-2011. AB - BACKGROUND: The aim of this study was to explore hip fracture (HFx) incidence in the Veneto Region of Italy, looking at potential differences with the national data. METHODS: We analyzed HFx incidence for people aged 65years or over, in years 2000-2011, using data from the Regional Hospitalization Database. Patients were stratified by sex, calendar year and 5-year age class. Data for the single provinces of the Region were also obtained. Absolute number of HFx, crude incidence for 10,000 inhabitants and age-standardized fracture rates were calculated. RESULTS: During the study period, there were 53,917 hospitalizations for HFx (77.7% in females). In the whole 11year period of observation, the absolute HFx number increased by 17.7% in males and 10.6% females, respectively. However, age-standardized incidence rates declined by 18% in the same period (IRR 0.82, 95% CI 0.78-0.87). This decreasing trend was almost identical through all the age-cohorts up to 84years. In the whole study period, HFx incidence was lower for Padova (IRR 0.63, 95% CI 0.60-0.66) and Verona (IRR 0.66, 95% CI 0.63-0.70) provinces as compared to the others. This regional profile was quite different with respect to the data published, for the same calendar years, for Italy as a whole, in spite of an almost identical demography of the population. CONCLUSIONS: HFx incidence is declining in the Veneto Region of Italy. Further studies, aimed to investigate factors involved in this figure are needed. PMID- 27363308 TI - Genomic variation at the tips of the adaptive radiation of Darwin's finches. AB - Adaptive radiation unfolds as selection acts on the genetic variation underlying functional traits. The nature of this variation can be revealed by studying the tips of an ongoing adaptive radiation. We studied genomic variation at the tips of the Darwin's finch radiation; specifically focusing on polymorphism within, and variation among, three sympatric species of the genus Geospiza. Using restriction site-associated DNA (RAD-seq), we characterized 32 569 single nucleotide polymorphisms (SNPs), from which 11 outlier SNPs for beak and body size were uncovered by a genomewide association study (GWAS). Principal component analysis revealed that these 11 SNPs formed four statistically linked groups. Stepwise regression then revealed that the first PC score, which included 6 of the 11 top SNPs, explained over 80% of the variation in beak size, suggesting that selection on these traits influences multiple correlated loci. The two SNPs most strongly associated with beak size were near genes associated with beak morphology across deeper branches of the radiation: delta-like 1 homologue (DLK1) and high-mobility group AT-hook 2 (HMGA2). Our results suggest that (i) key adaptive traits are associated with a small fraction of the genome (11 of 32 569 SNPs), (ii) SNPs linked to the candidate genes are dispersed throughout the genome (on several chromosomes), and (iii) micro- and macro-evolutionary variation (roots and tips of the radiation) involve some shared and some unique genomic regions. PMID- 27363307 TI - A Dietary Feedback System for the Delivery of Consistent Personalized Dietary Advice in the Web-Based Multicenter Food4Me Study. AB - BACKGROUND: Despite numerous healthy eating campaigns, the prevalence of diets high in saturated fatty acids, sugar, and salt and low in fiber, fruit, and vegetables remains high. With more people than ever accessing the Internet, Web based dietary assessment instruments have the potential to promote healthier dietary behaviors via personalized dietary advice. OBJECTIVE: The objectives of this study were to develop a dietary feedback system for the delivery of consistent personalized dietary advice in a multicenter study and to examine the impact of automating the advice system. METHODS: The development of the dietary feedback system included 4 components: (1) designing a system for categorizing nutritional intakes; (2) creating a method for prioritizing 3 nutrient-related goals for subsequent targeted dietary advice; (3) constructing decision tree algorithms linking data on nutritional intake to feedback messages; and (4) developing personal feedback reports. The system was used manually by researchers to provide personalized nutrition advice based on dietary assessment to 369 participants during the Food4Me randomized controlled trial, with an automated version developed on completion of the study. RESULTS: Saturated fatty acid, salt, and dietary fiber were most frequently selected as nutrient-related goals across the 7 centers. Average agreement between the manual and automated systems, in selecting 3 nutrient-related goals for personalized dietary advice across the centers, was highest for nutrient-related goals 1 and 2 and lower for goal 3, averaging at 92%, 87%, and 63%, respectively. Complete agreement between the 2 systems for feedback advice message selection averaged at 87% across the centers. CONCLUSIONS: The dietary feedback system was used to deliver personalized dietary advice within a multi-country study. Overall, there was good agreement between the manual and automated feedback systems, giving promise to the use of automated systems for personalizing dietary advice. TRIAL REGISTRATION: Clinicaltrials.gov NCT01530139; https://clinicaltrials.gov/ct2/show/NCT01530139 (Archived by WebCite at http://www.webcitation.org/6ht5Dgj8I). PMID- 27363309 TI - Effective separation of single-walled carbon nanotubes and their very different electrochemical behaviours. AB - The electrochemical behaviors of m- and s-SWNTs obtained from as-prepared SWNTs using a novel binaphthyl based separation agent were studied. The s-SWNTs show higher capacitance but lower electrocatalytic activity, while m-SWNTs show the opposite. Their electrochemical properties can be further interconverted through changing the DOS by electron or hole doping. PMID- 27363310 TI - Incidence of tramadol shopping behavior in a retrospective cohort of chronic non cancer pain patients in France. AB - PURPOSE: Opioid analgesic use in chronic non-cancer pain (CNCP) is increasingly prevalent, but the benefits and risks are inadequately understood. In France, tramadol is one of the most used prescription opioids, but studies on its misuse liability in CNCP are still lacking. The aim was to assess the incidence of tramadol shopping behavior in CNCP patients and to identify the associated risk factors. METHODS: A retrospective cohort of CNCP patients aged 18 years and older treated by tramadol for at least six consecutive months between 2005 and 2013 from a sample of the French Health Insurance database was established. Doctor shopping was defined as at least 1 day of overlapping prescriptions written by two or more different prescribers and filled in at least three different pharmacies. RESULTS: A total of 3505 CNCP patients were included with a majority of women (66.4%) and a mean age of 66.4 +/- 14.7 years. The median tramadol treatment duration was 260 [interquartile range: 211-356] days. The 1-year incidence rate of tramadol shopping behavior was 1.0% [95%CI: 0.7-1.5]. On multivariate analysis, risk factors associated with tramadol shopping behavior were age (hazard ratio [HR] = 7.4 [95%CI: 2.8-19.7] for age <40, HR = 2.8 [95%CI: 1.0-7.7] for 40 <= age < 50, versus age >=50), low-income status (HR = 8.5 [95%CI: 3.6-20.5]), and prior use of strong opioids (HR = 5.7 [95%CI: 1.9-17.0]). CONCLUSION: Tramadol shopping behavior incidence appears low in CNCP patients but may represent a public health concern given the widespread use of tramadol. Education and best monitoring of high-risk patients are needed to reduce doctor shopping. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27363311 TI - Slide shows vs graphic tablet live drawing for anatomy teaching. AB - INTRODUCTION: Blackboard drawing is the traditional and still widely learned method for anatomy teachers. However, for practical reasons, more and more lessons are done using slide shows. New digital learning tools are developed to create a more attractive teaching method. The objective of this study was to compare the use of graphic tablet live drawing versus slide shows. METHODS: Sixty five second-year students of the Faculty of Medicine participated in this study during their first semester of 2013-2014 academic year. The selected lecture dealt about neuroanatomy; two brain sections were taught: median sagittal and transverse. The sagittal section was presented via a slide show. The transverse section was taught using a graphics tablet using drawing software. Students were evaluated three times: before the lecture, immediately after the lecture and 8 weeks later. Means were compared using a t-test. RESULTS: Scores were significantly higher immediately after the lecture and 8 weeks later tests in comparing the transverse section (using the graphics tablet) versus the sagittal section (using PowerPoint(r)). Student satisfaction regarding the use of the tablet was high. CONCLUSION: The graphics tablet is a usable and efficient drawing tool in anatomy teaching. This tool requires a specific teacher training and preparation. PMID- 27363312 TI - Daily vancomycin dose requirements as a continuous infusion in obese versus non obese SICU patients. AB - BACKGROUND: Limited data are available assessing vancomycin concentrations in obese critically ill patients. Currently, there are no studies evaluating dosing requirements in this population who receive vancomycin administered as a continuous infusion (CI). The aim of this study was to assess whether there was a difference in the weight-based maintenance dose required to reach a therapeutic vancomycin concentration at 24 hours when given as a CI in obese versus non-obese critically ill patients. METHODS: A retrospective cohort study of adult obese patients admitted to the SICU between 2013 and 2015 receiving a vancomycin CI (CIV), and with 24-hour serum measurements were included. Obese patients (body mass index (BMI) >=35 kg/m(2)) were matched with non-obese patients (BMI <30 kg/m(2)) based on renal function, age and acute physiology and chronic health evaluation (APACHE)-II score at admission. All patients in this study received a loading dose of 25 mg/kg then a maintenance dose based on renal function according to the protocol. The study was approved by the Institutional Review Board. The primary outcome was the weight-based total daily maintenance dose required to achieve a vancomycin level of 20 mg/L. The secondary endpoints included the achievement of a therapeutic level at 24 hours. RESULTS: Twenty-six matched pairs of patients met the inclusion criteria. Of these, 17 pairs had preserved renal function and 9 pairs required continuous venovenous hemofiltration. Mean BMI was 40.9 kg/m(2) in obese and 24.8 kg/m(2) in non-obese patients. To achieve a vancomycin concentration of 20 mg/L, the weight-based daily maintenance dose in obese patients was 25.6 mg/kg versus 43.8 mg/kg in non obese patients (p <0.01). Therapeutic 24-hour levels were achieved in 24/26 obese versus 23/26 no-obese patients (p = 0.63). Mean 24-hour vancomycin level was 20.3 +/- 3.81 mcg/ml in obese compared to 20.03 +/- 3.79 mcg/ml in non-obese patients (p = 0.77). Mean daily maintenance doses required to achieve a level of 20 mcg/ml were 2961 +/- 1670 mg in obese compared to 3189 +/- 1600.69 mg in non-obese (p = 0.61). CONCLUSIONS: The results of our study suggest that critically ill obese patients treated with CIV required a significantly lower maintenance dose per unit of body weight than non-obese patients to achieve the same target level. PMID- 27363314 TI - Molecular chaperones: functional mechanisms and nanotechnological applications. AB - Molecular chaperones are a group of proteins that assist in protein homeostasis. They not only prevent protein misfolding and aggregation, but also target misfolded proteins for degradation. Despite differences in structure, all types of chaperones share a common general feature, a surface that recognizes and interacts with the misfolded protein. This and other, more specialized properties can be adapted for various nanotechnological purposes, by modification of the original biomolecules or by de novo design based on artificial structures. PMID- 27363315 TI - The synthesis of [(PbSe)1+delta]m(TiSe2)n[(SnSe2)1+gamma]m(TiSe2)n heterostructures with designed nanoarchitectures by self assembly of amorphous precursors. AB - Targeted heterostructures containing intergrown two dimensional (2D) layers of 3 different constituent layers, SnSe2, PbSe and TiSe2, were prepared by controlling the composition and sequence of elemental bilayers within a designed precursor. Varying the structure of the precursor enabled the number of structural units of each constituent and the sequence of crystalline 2D layers to be precisely controlled. The stacking of the 2D layers, their structures, and the segregation of the elements between them were determined using X-ray diffraction and electron microscopy techniques, with the observed sequence of the 2D layers consistent with the targeted intergrowth. This ability to prepare targeted heterostructures is critical, since the number of possible configurations in the final compound increases rapidly as the number of constituents increases, from almost 60 000 with two constituents to over 130 million with three constituents and to over 35 billion with four constituents for 20 or fewer distinct layers in the unit cell. This general route for synthesizing specific multiple component heterostructures will accelerate the feedback loop in this growing research area, permitting theorists to assume specific structures in the search for enhanced properties and providing experimentalists with crystallographically aligned samples to test these predictions. PMID- 27363313 TI - Pharmacokinetics and Safety Assessment of l-Tetrahydropalmatine in Cocaine Users: A Randomized, Double-Blind, Placebo-Controlled Study. AB - Cocaine use disorder (CUD) remains a significant public health challenge. l Tetrahydropalmatine (l-THP), a well-tolerated and nonaddictive compound, shows promise for the management of CUD. Its pharmacologic profile includes blockade at dopamine and other monoamine receptors and attenuation of cocaine self administration, reinstatement, and rewarding properties in rats. This study evaluated the safety of l-THP in human cocaine users and its influence on the safety and pharmacokinetics (PK) of cocaine. Twenty-four cocaine-using adult men were randomized to receive l-THP (30 mg twice a day orally) or placebo double blind for 4 days, with an intranasal cocaine (40 mg) challenge on the fourth day. Safety and tolerability were evaluated using vital signs, ECG, clinical laboratory tests, and standardized self-report instruments. Peripheral venous blood was collected periodically and later assayed for l-THP and cocaine using highly sensitive and specific ultraperformance liquid chromatography-fluorescence detection (UPLC-FLD) methods. Twenty subjects completed the study, of whom 19 provided complete PK data. The short 3.5-day course of l-THP was safe and well tolerated and did not affect cocaine's PK or its acute cardiovascular effects. The cocaine AUC0->infinity was 211.5 and 261.4 h.ng/mL, and the Cmax was 83.3 and 104.5 ng/mL for the l-THP and placebo groups, respectively. In addition there were no significant differences in the number of side effects reported in each group (l-THP group 22 [48%], placebo group 24 [52%]) or vital signs including, heart rate, blood pressure, complete blood count, or ECG. These findings suggest that oral THP has promise for further development as a treatment for CUD. PMID- 27363316 TI - Anatomy, nutritional value and cell wall chemical analysis of foliage leaves of Guadua chacoensis (Poaceae, Bambusoideae, Bambuseae), a promising source of forage. AB - BACKGROUND: The present study combines morphological and anatomical studies, cell wall chemical composition analysis, as well as assessment of the nutritional value of Guadua chacoensis foliage leaves. RESULTS: Foliage leaves of G. chacoensis are a promising source of forage because: (a) as a native woody bamboo, it is adapted to and helps maintain environmental conditions in America; (b) leaf anatomical studies exhibit discontinuous sclerenchyma, scarcely developed, while pilose indumentum, silica cells, prickles and hooks are also scarce; (c) it has a high protein content, similar to that of Medicago sativa, while other nutritional parameters are similar to those of common forages; and (d) glucuronoarabinoxylan, the major extracted polysaccharide, has one-third of the 4-linked beta-d-xylopyranosyl units of the backbone substituted mainly with alpha-l-arabinofuranose as single stubs or non-reducing end of short chains, but also 5-linked alpha-l-arabinofuranose units, terminal beta-d-xylopyranose and d galactopyranose units, as well as alpha-d-glucuronic acid residues and small amounts of its 4-O-methylated derivative. CONCLUSION: These results constitute the first report on this species, and as culms are utilized in constructions and crafts, the remaining leaves, when used as forage, constitute a byproduct that allows an additional income opportunity. (c) 2016 Society of Chemical Industry. PMID- 27363326 TI - Zika virus and the 2016 Olympic Games - Evidence-based projections derived from dengue do not support cancellation. PMID- 27363327 TI - Systematic review of loperamide: No proof of antibiotics being superior to loperamide in treatment of mild/moderate travellers' diarrhoea. AB - Looking at the worldwide emergency of antimicrobial resistance, international travellers appear to have a central role in spreading the bacteria across the globe. Travellers' diarrhoea (TD) is the most common disease encountered by visitors to the (sub)tropics. Both TD and its treatment with antibiotics have proved significant independent risk factors of colonization by resistant intestinal bacteria while travelling. Travellers should therefore be given preventive advice regarding TD and cautioned about taking antibiotics: mild or moderate TD does not require antibiotics. Logical alternatives are medications with effects on gastrointestinal function, such as loperamide. The present review explores literature on loperamide in treating TD. Adhering to manufacturer's dosage recommendations, loperamide offers a safe and effective alternative for relieving mild and moderate symptoms. Moreover, loperamide taken singly does no predispose to contracting MDR bacteria. Most importantly, we found no proof that would show antibiotics to be significantly more effective than loperamide in treating mild/moderate TD. PMID- 27363328 TI - Atrial fibrillation and dementia: Do risk factors matter? PMID- 27363330 TI - Congenital renal anomalies in cloacal exstrophy: Is there a difference? AB - INTRODUCTION: Cloacal exstrophy (CE) is the most severe manifestation of the epispadias-exstrophy spectrum. Previous studies have indicated an increased rate of renal anomalies in children with classic bladder exstrophy (CBE). Given the increased severity of the CE defect, it was hypothesized that there would be an even greater incidence among these children. OBJECTIVE: The primary objective was to characterize renal anatomy in CE patients. Two secondary objectives were to compare these renal anatomic findings in male and female patients, and female patients with and without Mullerian anomalies. STUDY DESIGN: An Institutional Review Board-approved retrospective review of 75 patients from an institutional exstrophy database. Data points included: age at analysis, sex, and renal and Mullerian anatomy. Abnormal renal anatomy was defined as a solitary kidney, malrotation, renal ectopia, congenital cysts, duplication, and/or proven obstruction. Abnormal Mullerian anatomy was defined as uterine or vaginal duplication, obstruction, and/or absence. RESULTS: The Summary Table presents demographic data and renal anomalies. Males were more likely to have renal anomalies. Mullerian anomalies were present in 65.7% of female patients. Girls with abnormal Mullerian anatomy were 10 times more likely to have renal anomalies than those with normal Mullerian anatomy (95% CI 1.1-91.4, P = 0.027). DISCUSSION: Patients with CE had a much higher rate of renal anomalies than that reported for CBE. Males and females with Mullerian anomalies were at greater risk than females with normal uterine structures. Mesonephric and Mullerian duct interaction is required for uterine structures to develop normally. It has been proposed that women with both Mullerian and renal anomalies be classified separately from other uterine malformations on an embryonic basis. In these patients, an absent or dysfunctional mesonephric duct has been implicated as potentially causal. This provided an embryonic explanation for uterine anomalies in female CE patients. There were also clinical implications. Women with renal agenesis and uterine anomalies were more likely to have endometriosis than those with isolated uterine anomalies, but were also more likely to have successful pregnancies. Males may have had an analogous condition with renal agenesis and seminal vesicle cysts. Future research into long-term kidney function in this population, uterine function, and possible male sexual duct malformation is warranted. CONCLUSION: Congenital renal anomalies occurred frequently in children with CE. They were more common in boys than in girls. Girls with abnormal Mullerian anatomy were more likely to have anomalous renal development. Mesonephric duct dysfunction may be embyologically responsible for both renal and Mullerian maldevelopment. PMID- 27363329 TI - Increased pediatric sub-specialization is associated with decreased surgical complication rates for inpatient pediatric urology procedures. AB - INTRODUCTION: Increased case volumes and training are associated with better surgical outcomes. However, the impact of pediatric urology sub-specialization on perioperative complication rates is unknown. OBJECTIVES: To determine the presence and magnitude of difference in rates of common postoperative complications for elective pediatric urology procedures between specialization levels of urologic surgeons. The Nationwide Inpatient Sample (NIS), a nationally representative administrative database, was used. STUDY DESIGN: The NIS (1998 2009) was retrospectively reviewed for pediatric (<=18 years) admissions, using ICD-9-CM codes to identify urologic surgeries and National Surgical Quality Improvement Program (NSQIP) inpatient postoperative complications. Degree of pediatric sub-specialization was calculated using a Pediatric Proportion Index (PPI), defined as the ratio of children to total patients operated on by each provider. The providers were grouped into PPI quartiles: Q1, 0-25% specialization; Q2, 25-50%; Q3, 50-75%; Q4, 75-100%. Weighted multivariate analysis was performed to test for associations between PPI and surgical complications. RESULTS: A total of 71,479 weighted inpatient admissions were identified. Patient age decreased with increasing specialization: Q1, 7.9 vs Q2, 4.8 vs Q3, 4.8 vs Q4, 4.6 years, P < 0.01). Specialization was not associated with race (P > 0.20), gender (P > 0.50), or comorbidity scores (P = 0.10). Mortality (1.5% vs 0.2% vs 0.3% vs 0.4%, P < 0.01) and complication rates (15.5% vs 11.7% vs 9.6% vs 10.9%, P < 0.0001) both decreased with increasing specialization. Patients treated by more highly specialized surgeons incurred slightly higher costs (Q2, +4%; Q3, +1%; Q4 + 2%) but experienced shorter length of hospital stay (Q2, -5%; Q3, -10%; Q4, -3%) compared with the least specialized providers. A greater proportion of patients treated by Q1 and Q3 specialized urologists had CCS >=2 than those seen by Q2 or Q4 urologists (12.5% and 12.2%, respectively vs 8.4% and 10.9%, respectively, P = 0.04). Adjusting for confounding effects, increased pediatric specialization was associated with decreased postoperative complications: Q2 OR 0.78, CI 0.58-1.05; Q3 OR 0.60, CI 0.44-0.84; Q4 OR 0.70, CI 0.58-0.84; P < 0.01. DISCUSSION: Providers with proportionally higher volumes of pediatric patients achieved better postoperative outcomes than their less sub-specialized counterparts. This may have arisen from increased exposure to pediatric anatomy and physiology, and greater familiarity with pediatric techniques. LIMITATION: The NIS admission-based retrospective design did not enable assessment of long-term outcomes, repeated admissions, or to track a particular patient across time. The study was similarly limited in evaluating the effect of pre-surgical referral patterns on patient distributions. CONCLUSIONS: Increased pediatric sub-specialization among urologists was associated with a decreased risk of mortality and surgical complications in children undergoing inpatient urologic procedures. PMID- 27363331 TI - Checklist assessment tool to evaluate suitability and success of neonatal clamp circumcision: A prospective study. AB - BACKGROUND: The American Academy of Pediatrics (AAP) Task Force on Circumcision has called for the development of standards of trainee proficiency in regards to evaluation and technique for neonatal clamp circumcision (NCC). At the present time, there is no standardized or general consensus on patient selection for NCC. An improved method to evaluate newborns for NCC is an important first step in this process. Therefore, the authors collaborated to identify criteria useful in the evaluation of newborns for suitability for NCC, and for assessment of success after NCC and have named it "Checklist Assessment for Neonatal Clamp Circumcision Suitability." METHODS: A national multi-institutional collaboration was created to obtain consensus on objective criteria for use in determining patient suitability for NCC, and for assessing post-circumcision success outcomes. Criteria included elements from detailed medical history, bedside physical examination, and post-circumcision follow-up. Patients desiring NCC were enrolled consecutively and prospectively. The Checklist was followed to determine which newborns were suited to NCC, and NCC was done in those cases. The patients' caretakers were given post-circumcision care instructions and a follow-up appointment. Post circumcision, the Checklist was followed to determine if the procedure resulted in a successful circumcision or if there were complications. RESULTS: A total of 193 cases were enrolled prospectively and consecutively from January 2014 through October 2014. The mean age was 15 days (1-30 days). Of those 193 patients, 129 (67%) were deemed suitable for circumcision and underwent NCC. Post-circumcision assessment showed a 100% success rate with no complications. A total of 64 (23%) cases were deemed unsuitable for NCC because at least one checklist criterion was not satisfied, most commonly: penile torsion (n = 25), chordee (n = 19), and penoscrotal webbing (n = 19). DISCUSSION: Use of the Checklist in the present study has demonstrated a method of patient screening resulting in a 100% success rate with no complications. A high proportion of patients (33%) was identified as unsuited for NCC; however, the patient population consisted of newborn males referred to pediatric urology, and thus does not represent the general population, which is expected to have a lower proportion of unsuited patients. Regardless, the Checklist has the potential to enhance the decision-making process for both urologic and non-urologic care providers. CONCLUSIONS: The use of the "Checklist Assessment for Neonatal Clamp Circumcision Suitability" assessment tool improves identification of patients unsuited for NCC and thereby potentially decreases the likelihood of circumcision related complications. PMID- 27363332 TI - Structural differences between amyloid beta oligomers. AB - In Alzheimer's disease, soluble Abeta oligomers are believed to play important roles in the disease pathogenesis, and their levels correlate with cognitive impairment. We have previously shown that Abeta oligomers can be categorized into multiple structural classes based on their reactivity with conformation-dependent antibodies. In this study, we analyzed the structures of Abeta40 oligomers belonging to two of these classes: fibrillar and prefibrillar oligomers. We found that fibrillar oligomers were similar in structure to fibrils but were less stable towards denaturation while prefibrillar oligomers were found to be partially disordered. These results are consistent with previously proposed structures for both oligomer classes while providing additional structural information. PMID- 27363333 TI - Perfluorooctane sulfonate-induced insulin resistance is mediated by protein kinase B pathway. AB - Perfluorooctane sulfonate (PFOS), a persistent organic pollutant, is blamed to be associated with the incidence of insulin resistance in the general human population. In this study, we found that PFOS inhibited the phosphorylation and activation of protein kinase B (AKT), a key mediator of cellular insulin sensitivity, in human hepatoma HepG2 cells. The mRNA level of the gluconeogenic gene PEPCK, a downstream target gene of AKT, was increased in PFOS-treated cells. Due to stimulated gluconeogenesis, insulin-stimulated glucose uptake was decreased in HepG2 cells. In our previous study, we found that PFOS disturbed autophagy in HepG2 cells. We proposed that PFOS could inhibit the activation of AKT through inhibiting mTORC2, a key regulator of autophagy. In this study, we found that the levels of triglyceride were increased in HepG2 cells. PFOS-induced accumulation of hepatic lipids also contributed to the inhibition of AKT. Eventually, the inhibition of AKT led to insulin resistance in PFOS-treated cells. Our data would provide new mechanistic insights into PFOS-induced hepatic insulin resistance. PMID- 27363334 TI - MiR-27b is epigenetically downregulated in tamoxifen resistant breast cancer cells due to promoter methylation and regulates tamoxifen sensitivity by targeting HMGB3. AB - MiR-27b downregulation is significantly associated with tamoxifen resistance in breast cancer cells. However, how it is downregulated in tamoxifen resistant (TamR) breast cancer cells and its downstream regulation were not clear. By performing MSP assay and QRT-PCR analysis with the use of 5-AZA-dC, a DNA methyltransferase inhibitor, we observed that TamR MCF-7 cells had significantly higher levels of methylation in the miR-27b promoter region than tamoxifen sensitive MCF-7 (TamS) cells and demethylation restored miR-27b expression. Re expression of miR-27b sensitized TamR MCF-7 cells to tamoxifen, inhibited invasion and reversed epithelial-mesenchymal transition (EMT)-like properties. By using bioinformatics analysis and following dual luciferase and western blot analysis, this study confirmed a direct regulation of miR-27b on HMGB3 expression by binding to the 3'UTR. In addition, this study also found that silencing of HMGB3 indeed partially phenocopied the effects of miR-27b in reducing tamoxifen resistance and cell invasion and in reversing EMT-like properties. Therefore, we infer that HMGB3 is a functional target of miR-27b in modulation of tamoxifen resistance and EMT. PMID- 27363336 TI - High-throughput screening identifies artesunate as selective inhibitor of cancer stemness: Involvement of mitochondrial metabolism. AB - Cancer stem cells (CSCs) have robust systems to maintain cancer stemness and drug resistance. Thus, targeting such robust systems instead of focusing on individual signaling pathways should be the approach allowing the identification of selective CSC inhibitors. Here, we used the alkaline phosphatase (ALP) assay to identify inhibitors for cancer stemness in induced cancer stem-like (iCSCL) cells. We screened several compounds from natural product chemical library and evaluated hit compounds for their efficacy on cancer stemness in iCSCL tumorspheres. We identified artesunate, an antimalarial drug, as a selective inhibitor of cancer stemness. Artesunate induced mitochondrial dysfunction that selectively inhibited cancer stemness of iCSCL cells, indicating an essential role of mitochondrial metabolism in cancer stemness. PMID- 27363335 TI - A bispecific anti-ErbB2 antibody potently induces ErbB2 internalization and suppresses ErbB2-overexpressing tumor growth. AB - The anti-ErbB2 humanized antibody trastuzumab was approved for ErbB2-positive metastatic gastric and gastro-esophageal junction cancer in 2010. Despite the effectiveness of trastuzumab, its efficacy remains variable and often modest. Thus, there is an urgent need to improve ErbB2-targeting therapy. Down-regulation of surface receptors induced by monoclonal antibody (mAb) contributes to its antitumor efficacy. Previous studies have demonstrated that if two anti-ErbB2 mAbs did not compete with each other for binding to ErbB2, the combination of them can enhance ErbB2 internalization. In the present study, we investigated ErbB2 internalization-inducing ability of non-competitive anti-ErbB2 mAb combinations and surprisingly found that most of the mAb combinations tested did not down-regulate ErbB2. Only 4 of 18 non-competitive mAb pairs efficiently induced ErbB2 internalization. Interestingly, although the non-competitive anti ErbB2 mAbs trastuzumab and pertuzumab, either alone or in combination, were ineffective at inducing ErbB2 internalization, TPL, a bispecific antibody engineered from trastuzumab and pertuzumab, potently down-regulated the ErbB2 molecule. Importantly, TPL exhibited a far greater antitumor effect on ErbB2 overexpressing gastric cancer cell line than trastuzumab plus pertuzumab, suggesting that it may be a promising agent for the treatment of gastric cancer. PMID- 27363337 TI - Biochanin-A antagonizes the interleukin-1beta-induced catabolic inflammation through the modulation of NFkappaB cellular signaling in primary rat chondrocytes. AB - Biochanin-A, a phytoestrogen derived from herbal plants, protected from the IL 1beta-induced loss of proteoglycans through the suppression of matrix degrading enzymes such as matrix metalloproteinase (MMP)-13, MMP-3, MMP-1, and ADAMTS-5 in primary rat chondrocytes and the knee articular cartilage. It also suppressed the expression of IL-1beta-induced catabolic factors such as nitric oxide synthase 2, cyclooxygenase-2, prostaglandin E2, and inflammatory cytokines. Furthermore, biochanin-A suppressed the IL-1beta-induced phosphorylation of NFkappaB, and inhibited its nuclear translocation in primary rat chondrocytes. These results indicate that biochanin-A antagonizes the IL-1beta-induced catabolic effects through its anti-inflammatory activity that involves the modulation of NFkappaB signaling. PMID- 27363338 TI - TCR-contacting residues orientation and HLA-DRbeta* binding preference determine long-lasting protective immunity against malaria. AB - Fully-protective, long-lasting, immunological (FPLLI) memory against Plasmodium falciparum malaria regarding immune protection-inducing protein structures (IMPIPS) vaccinated into monkeys previously challenged and re-challenged 60 days later with a lethal Aotus monkey-adapted P. falciparum strain was found to be associated with preferential high binding capacity to HLA-DRbeta1* allelic molecules of the major histocompatibility class II (MHC-II), rather than HLA DRbeta3*, beta4*, beta5* alleles. Complete PPIIL 3D structure, a longer distance (26.5 A +/- 1.5 A) between residues perfectly fitting into HLA-DRbeta1*PBR pockets 1 and 9, a gauche(-) rotamer orientation in p8 TCR-contacting polar residue and a larger volume of polar p2 residues was also found. This data, in association with previously-described p3 and p7 apolar residues having gauche(+) orientation to form a perfect MHC-II-peptide-TCR complex, determines the stereo electronic and topochemical characteristics associated with FPLLI immunological memory. PMID- 27363339 TI - Long non-coding RNA TUG1 acts as a miR-26a sponge in human glioma cells. AB - BACKGROUND: Long non-coding RNA taurine upregulated gene 1 (TUG1) acts as an important regulator in cancer pathogenesis; however, its functional mechanism in glioma development remains unclear. This study aims to explore the potential function of TUG1 in glioma by sponging miR-26a. METHODS: The expression of TUG1, miR-26a, and phosphatase and tensin homolog (PTEN) in 20 paired glioma tissues was detected by quantitative real-time PCR and subjected to correlation analysis. Bioinformatics analysis was performed by using DIANA Tools. Abnormal TUG1 expression was conducted in two glioma cells to analyze its regulation on miR-26a and PTEN using real-time PCR, western blot, and luciferase reporter assay. RESULTS: TUG1 expression was confirmed to be upregulated in glioma tissues, and showed an inverse correlation with downregulated miR-26a. TUG1 could negatively regulate the expression of miR-26a in glioma cells. The bioinformatics prediction revealed putative miR-26a binding sites within TUG1 transcripts. Further experiments demonstrated the positive regulation of TUG1 on the miR-26a target, PTEN, wherein TUG1 could inhibit the negative regulation of miR-26a on PTEN by binding its 3'UTR. Additionally, the expression of PTEN was also upregulated in glioma tissues, showing a positive or negative correlation with TUG1 or miR-26a, respectively. CONCLUSION: TUG1 could serve as a miR-26a sponge in human glioma cells, contributing to the upregulation of PTEN. This study revealed a new TUG1/miR-26a/PTEN regulatory mechanism and provided a further understanding of the tumor-suppressive role of TUG1 in glioma development. PMID- 27363341 TI - Proteasome inhibitor PS-341 limits macrophage necroptosis by promoting cIAPs mediated inhibition of RIP1 and RIP3 activation. AB - Apoptotic and necrotic macrophages have long been known for their existence in atherosclerotic lesions. However, the mechanisms underlying the choice of their death pattern have not been fully elucidated. Here, we report the effects of PS 341, a potent and specific proteasome inhibitor, on the cell death of primary bone marrow-derived macrophages (BMDMs) in vitro. The results showed that PS-341 could not induce macrophage apoptosis or promote TNF-induced macrophage apoptosis, on the other hand, PS-341 could significantly inhibit macrophage necroptosis induced by TNF and pan-caspase inhibitor z-VAD treatment. Remarkably, high-dose of PS-341 showed similar inhibitory effects on macrophage necroptosis comparable to that of kinase inhibition of RIP1 through specific inhibitor Nec-1 or inhibition of RIP3 via specific genetical ablation. Furthermore, the degradation of cellular inhibitor of apoptosis proteins (cIAPs) was suppressed by PS-341, which could antagonize the activation of RIP1 kinase via post translational mechanism. Further evidences demonstrated reduced levels of both RIP1 and RIP 3 upon PS-341 treatment, concomitantly, a more strong association of RIP1 with cIAPs and less with RIP3 was found following PS-341 treatment, these findings suggested that PS-341 may disrupt the formation of RIP1-RIP3 complex (necrosome) through stabilizing cIAPs. Collectively, our results indicated that the proteasome-mediated degradation of cIAPs could be inhibited by PS-341 and followed by limited RIP1 and RIP3 kinase activities, which were indispensable for necroptosis, thus eliciting a significant necroptosis rescue in BMDMs in vitro. Overall, our study has identified a new role of PS-341 in the cell death of BMDMs and provided a novel insight into the atherosclerotic inflammation caused by proteasome-mediated macrophage necroptosis. PMID- 27363340 TI - miR-199b-5p modulates BMSC osteogenesis via suppressing GSK-3beta/beta-catenin signaling pathway. AB - miR-199b-5p is up-regulated significantly during the osteogenesis process in human bone marrow stromal cells (BMSCs). Inhibiting miR-199b-5p notably reduces while over-expressing miR-199b-5p promotes the BMSCs osteoblast differentiation, suggested by the alternations of osteogenic genes expression, ALP activity and the ARS-stained mineral nodules. miR-199b-5p exerts its role in BMSC osteogenesis most probably through the GSK-3beta/beta-catenin signaling pathway. In conclusion, the present study revealed for the first time that miR-199b-5p plays a positive role in osteoblast differentiation. PMID- 27363342 TI - Discovery of pathogenic variants in a large Korean cohort of inherited muscular disorders. AB - Inherited muscular disorders (IMDs) are clinically and genetically heterogeneous genetic disorders. We investigated the mutational spectrum and genotype-phenotype correlations in Korean patients with IMD. We developed a targeted panel of 69 known IMD genes and recruited a total of 209 Korean patients with IMD. Targeted capture sequencing identified 994 different variants. Among them, 98 variants were classified as pathogenic/likely pathogenic variants; 38 were novel variations. A total of 39 patients had the pathogenic/likely pathogenic variants. Among them, 75 (36%) patients were genetically confirmed, and 18 (9%) patients had one heterozygous variant of recessive myopathy. However, two genetically confirmed patients had an additional heterozygous variant of another recessive myopathy. Four patients with one heterozygous variant of a recessive myopathy showed different phenotypes, compared with the known phenotype of the identified gene. The major causative genes of Korean patients with IMDs were DMD (19 patients), COL6A1 (9), DYSF (9), GNE (7), LMNA (7), CAPN3 (6), and RYR1 (5). This study showed the mutational and clinical spectra in Korean patients with IMD and confirmed the usefulness of strategies utilizing targeted sequencing. PMID- 27363343 TI - Does the addition of saline infusion sonohysterography to transvaginal ultrasonography prevent unnecessary hysteroscopy in premenopausal women with abnormal uterine bleeding? AB - This observational case series in 65 premenopausal women with abnormal uterine bleeding evaluated whether transvaginal ultrasound followed by saline infusion sonohysterography (SIS) prevented unnecessary hysteroscopy. Although SIS indicated that hysteroscopy was unnecessary in eight women, this benefit was offset by the invasive nature of the scan, the number of endometrial abnormalities falsely detected by SIS and the cost of the additional investigation. PMID- 27363345 TI - Grazing effects on ecosystem CO2 fluxes differ among temperate steppe types in Eurasia. AB - Grassland ecosystems play a critical role in regulating CO2 fluxes into and out of the Earth's surface. Whereas previous studies have often addressed single fluxes of CO2 separately, few have addressed the relation among and controls of multiple CO2 sub-fluxes simultaneously. In this study, we examined the relation among and controls of individual CO2 fluxes (i.e., GEP, NEP, SR, ER, CR) in three contrasting temperate steppes of north China, as affected by livestock grazing. Our findings show that climatic controls of the seasonal patterns in CO2 fluxes were both individual flux- and steppe type-specific, with significant grazing impacts observed for canopy respiration only. In contrast, climatic controls of the annual patterns were only individual flux-specific, with minor grazing impacts on the individual fluxes. Grazing significantly reduced the mean annual soil respiration rate in the typical and desert steppes, but significantly enhanced both soil and canopy respiration in the meadow steppe. Our study suggests that a reassessment of the role of livestock grazing in regulating GHG exchanges is imperative in future studies. PMID- 27363344 TI - Comparison of Capillary and Venous Plasma Drug Concentrations After Repeated Administration of Risperidone, Paliperidone, Quetiapine, Olanzapine, or Aripiprazole. AB - Quantification of blood levels of antipsychotic drugs may be useful for managing medication therapy. This open-label, parallel-group study was performed to compare finger-stick-based capillary with corresponding venous plasma concentrations for risperidone, paliperidone, quetiapine, olanzapine, and aripiprazole and their major metabolites after repeated dosing in patients with schizophrenia or related illnesses. Finger-stick-based capillary and venous blood samples were collected at various times within a dosing interval. All drug concentration measurements in the derived plasma samples were performed with validated liquid chromatography-tandem mass spectrometry methods. Finger-stick based capillary and venous plasma drug concentrations after repeated dosing were generally similar. Olanzapine capillary plasma concentrations, however, were on average approximately 20% higher than venous concentrations, with a trend for a relatively greater difference occurring shortly after dosing. In addition, smaller capillary-venous differences were observed for extended-release and long acting intramuscular formulations and for aripiprazole, a drug with a long half life, compared with drugs administered as an immediate-release formulation (risperidone, olanzapine). After repeated dosing, plasma derived from finger stick-based blood was observed to be predictive of the venous concentrations. Capillary sampling may be an appropriate alternative to venous sampling to readily evaluate systemic drug concentrations. PMID- 27363346 TI - Understanding the atmospheric pressure ionization of petroleum components: The effects of size, structure, and presence of heteroatoms. AB - Understanding the composition of crude oil and its changes with weathering is essential when assessing its provenience, fate, and toxicity. High-resolution mass spectrometry (HRMS) has provided the opportunity to address the complexity of crude oil by assigning molecular formulae, and sorting compounds into "classes" based on heteroatom content. However, factors such as suppression effects and discrimination towards certain components severely limit a truly comprehensive mass spectrometric characterization, and, despite the availability of increasingly better mass spectrometers, a complete characterization of oil still represents a major challenge. In order to fully comprehend the significance of class abundances, as well as the nature and identity of compounds detected, a good understanding of the ionization efficiency of the various compound classes is indispensable. The current study, therefore, analyzed model compounds typically found in crude oils by high-resolution mass spectrometry with atmospheric pressure photoionization (APPI), atmospheric pressure chemical ionization (APCI), and electrospray ionization (ESI), in order to provide a better understanding of benefits and drawbacks of each source. The findings indicate that, overall, APPI provides the best results, being able to ionize the broadest range of compounds, providing the best results with respect to ionization efficiencies, and exhibiting the least suppression effects. However, just like in the other two sources, in APPI several factors have shown to affect the ionization efficiency of petroleum model compounds. The main such factor is the presence or absence of functional groups that can be easily protonated/deprotonated, in addition to other factors such as size, methylation level, presence of heteroatoms, and ring structure. Overall, this study evidences the intrinsic limitations and benefits of each of the three sources, and should provide the fundamental knowledge required to expand the power of crude oil analysis by high-resolution mass spectrometry. PMID- 27363347 TI - Effect of deforestation on stream water chemistry in the Skrzyczne massif (the Beskid Slaski Mountains in southern Poland). AB - The purpose of the study was to identify the factors affecting stream water chemistry in the small mountain catchments deforested to varying degrees, from 98.7 to 14.1%, due to long-term acid deposition. Water samples were collected monthly in 2013 and 2014 from 17 streams flowing across three distinct elevation zones in the Skrzyczne massif (Poland): Upper, Middle and Lower Forest Zone. Chemical and physical analyses, including the pH, electrical conductivity (EC), total mineral content (Mt), water temperature, and the concentrations of Ca(2+), Mg(2+), Na(+), K(+), HCO3(-), SO4(2-), Cl(-), and NO3(-), were conducted. Based on Principal Component Analysis (PCA), the most important factor affecting water chemistry was human impact associated with changes in pH, SO4(2-) concentration, and the concentration of most of the main ions. The substantial acidity of the studied environment contributed to the exclusion of natural factors, associated with changes in discharge, from the list of major factors revealed by PCA. All of the streams were characterized by very low EC, Mt, and low concentrations of the main ions such as Ca(2+) and HCO3(-). This is the effect of continuous leaching of solutes from the soils by acidic precipitation. The lowest parameter values were measured for the streams situated in the Upper Forest Zone, which is associated with greater acid deposition at the higher elevations. In the streams located in the Upper Forest Zone, a higher percentage of SO4(2-) occurred than in the streams situated in the Middle and Lower Forest Zones. However, the largest share of SO4(2-) was measured in the most deforested catchment. The saturation of the studied deforested catchment with sulfur compounds is reflected by a positive correlation between SO4(2-) and discharge. Hence, a forest acts as a natural buffer that limits the level of acidity in the natural environment caused by acidic atmospheric deposition. PMID- 27363349 TI - Contract Employees and EBPs in the Post-ACA Era. PMID- 27363348 TI - Alpha-tubulin enhanced renal tubular cell proliferation and tissue repair but reduced cell death and cell-crystal adhesion. AB - Adhesion of calcium oxalate (CaOx) crystals on renal tubular epithelial cells is a critical event for kidney stone disease that triggers many cascades of cellular response. Our previous expression proteomics study identified several altered proteins in MDCK renal tubular cells induced by CaOx crystals. However, functional significance of those changes had not been investigated. The present study thus aimed to define functional roles of such proteome data. Global protein network analysis using STRING software revealed alpha-tubulin, which was decreased, as one of central nodes of protein-protein interactions. Overexpression of alpha-tubulin (pcDNA6.2-TUBA1A) was then performed and its efficacy was confirmed. pcDNA6.2-TUBA1A could maintain levels of alpha-tubulin and its direct interacting partner, vimentin, after crystal exposure. Also, pcDNA6.2-TUBA1A successfully reduced cell death to almost the basal level and increased cell proliferation after crystal exposure. Additionally, tissue repair capacity was improved in pcDNA6.2-TUBA1A cells. Moreover, cell-crystal adhesion was reduced by pcDNA6.2-TUBA1A. Finally, levels of potential crystal receptors (HSP90, HSP70, and alpha-enolase) on apical membrane were dramatically reduced to basal levels by pcDNA6.2-TUBA1A. These findings implicate that alpha-tubulin has protective roles in kidney stone disease by preventing cell death and cell crystal adhesion, but on the other hand, enhancing cell proliferation and tissue repair function. PMID- 27363351 TI - Improving Social Security's Financial Capability Assessments. AB - When Social Security beneficiaries are incapable of managing their benefits, the agency can appoint a representative payee to administer benefits on their behalf. A committee of the Institute of Medicine was asked by the Social Security Administration to review the process by which financial capability determinations are made and to recommend improvements. The committee's conclusions and recommendations include the following: giving priority to real-world financial performance in assessing capability, providing clearer instructions to informants, developing systematic approaches to identifying beneficiaries at risk of incapability, exploring the use of a supervised direct payment option, and instituting regular data collection to assist in improving operations. PMID- 27363352 TI - AOT and Long-Term Use of Antipsychotics-2. PMID- 27363353 TI - AOT and Long-Term Use of Antipsychotics. PMID- 27363354 TI - AOT and Long-Term Use of Antipsychotics-3. PMID- 27363355 TI - AOT and Long-Term Use of Antipsychotics: In Reply. PMID- 27363356 TI - Compulsory Community Treatment and Homicide: Insufficient Evidence Now and in the Future. PMID- 27363357 TI - Documenting AOT Implementation: Misinformed Informants? In Reply. PMID- 27363358 TI - Documenting AOT Implementation: Misinformed Informants? PMID- 27363359 TI - Consultant Psychiatrists' Role in Ensuring High-Quality Care From Nonspecialists. PMID- 27363360 TI - News & Notes. PMID- 27363362 TI - Alignment-free microbial phylogenomics under scenarios of sequence divergence, genome rearrangement and lateral genetic transfer. AB - Alignment-free (AF) approaches have recently been highlighted as alternatives to methods based on multiple sequence alignment in phylogenetic inference. However, the sensitivity of AF methods to genome-scale evolutionary scenarios is little known. Here, using simulated microbial genome data we systematically assess the sensitivity of nine AF methods to three important evolutionary scenarios: sequence divergence, lateral genetic transfer (LGT) and genome rearrangement. Among these, AF methods are most sensitive to the extent of sequence divergence, less sensitive to low and moderate frequencies of LGT, and most robust against genome rearrangement. We describe the application of AF methods to three well studied empirical genome datasets, and introduce a new application of the jackknife to assess node support. Our results demonstrate that AF phylogenomics is computationally scalable to multi-genome data and can generate biologically meaningful phylogenies and insights into microbial evolution. PMID- 27363364 TI - Editorial. PMID- 27363363 TI - Nociception modulation by supraspinal group III metabotropic glutamate receptors. AB - The modulatory actions of glutamate, the main excitatory neurotransmitter in the central nervous system (CNS), are exerted through the activation of metabotropic glutamate receptors (mGluRs). Of the eight known mGluRs (mGluR1-8), group III mGluRs (mGluR4, mGluR6, mGluR7, and mGluR8) are less understood because of the lack of selective ligands. Except for mGluR6, group III mGluRs are widely distributed throughout the CNS. They are mainly located on presynaptic terminals where they inhibit neurotransmitter release at glutamatergic and gamma aminobutyric acid (GABA)ergic synapses. Their location at certain synapses is considered critical for normal CNS function, which makes them potential targets in neurological and psychiatric treatments. Novel ligands that are selective for group III mGluR subtypes have recently been developed. These compounds, which mainly target allosteric sites and act as positive or negative allosteric modulators (PAMs or NAMs) of glutamate transmission, are contributing to the understanding of the functional roles of group III mGluRs in a number of pathological conditions, such as epilepsy, anxiety, neurodegenerative diseases, and chronic pain. Moreover, the presence of group III mGluRs throughout the entire pain neuraxis and particularly in the descending system suggests that these endogenous substrates that extend from the cortex to the first spinal synapse are candidates for pain control. Recent data on chronic pain alleviation by group III mGluR ligands encourage further studies as pathological pain is one of the most troublesome diseases because of the current lack of satisfactory therapy. This review summarizes recent studies on group III mGluRs in animal models of chronic pain, which evidence an opposite modulation of mGluR7 and mGluR8 on pain responses and their capability to affect pain responses only in pathological states. This article is part of the special article series "Pain". PMID- 27363365 TI - Complexity from Simple Building Blocks: Engineering Large-scale Information processing Networks from Molecules. AB - Complexity in molecular systems can manifest itself either structurally or functionally. One of the more complex functions encountered in the natural world is that of information processing, or computation. Similarly, artificial cells will require this capacity to fully exploit their potential. Here I review the state of the art in the field, describe our contribution to this challenge in the framework of NCCR Molecular Systems Engineering, and propose an outlook for future efforts. PMID- 27363366 TI - From Photodriven Charge Accumulation to Fueling Enzyme Cascades in Molecular Factories. AB - In a multi-disciplinary team effort we gather experts on light-to-chemical energy conversion, artificial metalloenzymes, and bio-inspired polymer vesicles in order to construct molecular factories which produce added-value chemicals in an overall process fueled by solar energy. We outline our long-term vision and discuss specific challenges associated with this endeavor. PMID- 27363367 TI - Engineering and Assembly of Protein Modules into Functional Molecular Systems. AB - Synthetic biology approaches range from the introduction of unique features into organisms to the assembly of isolated biomacromolecules or synthetic building blocks into artificial biological systems with biomimetic or completely novel functionalities. Simple molecular systems can be based on containers on the nanoscale that are equipped with tailored functional modules for various applications in healthcare, industry or biological and medical research. The concept, or vision, of assembling native or engineered proteins and/or synthetic components as functional modules into molecular systems is discussed. The main focus is laid on the engineering of energizing modules generating chemical energy, transport modules using this energy to translocate molecules between compartments of a molecular system, and catalytic modules (bio-)chemically processing the molecules. Further key aspects of this discourse are possible approaches for the assembly of simple nanofactories and their applications in biotechnology and medical health. PMID- 27363368 TI - 'Active Surfaces' as Possible Functional Systems in Detection and Chemical (Bio) Reactivity. AB - This article presents design strategies to demonstrate approaches to generate functionalized surfaces which have the potential for application in molecular systems; sensing and chemical reactivity applications are exemplified. Some applications are proven, while others are still under active investigation. Adaptation and extension of our strategies will lead to interfacing of different type of surfaces, specific interactions at a molecular level, and possible exchange of signals/cargoes between them. Optimization of the present approaches from each of five research groups within the NCCR will be directed towards expanding the types of functional surfaces and the properties that they exhibit. PMID- 27363369 TI - Nucleocytoplasmic Transport: A Paradigm for Molecular Logistics in Artificial Systems. AB - Artificial organelles, molecular factories and nanoreactors are membrane-bound systems envisaged to exhibit cell-like functionality. These constitute liposomes, polymersomes or hybrid lipo-polymersomes that display different membrane-spanning channels and/or enclose molecular modules. To achieve more complex functionality, an artificial organelle should ideally sustain a continuous influx of essential macromolecular modules (i.e. cargoes) and metabolites against an outflow of reaction products. This would benefit from the incorporation of selective nanopores as well as specific trafficking factors that facilitate cargo selectivity, translocation efficiency, and directionality. Towards this goal, we describe how proteinaceous cargoes are transported between the nucleus and cytoplasm by nuclear pore complexes and the biological trafficking machinery in living cells (i.e. nucleocytoplasmic transport). On this basis, we discuss how biomimetic control may be implemented to selectively import, compartmentalize and accumulate diverse macromolecular modules against concentration gradients in artificial organelles. PMID- 27363370 TI - Interfacing Functional Systems. AB - The objective of molecular systems engineering is to move beyond functional components and primary systems, towards cumulate emergent properties in interfaced higher-order systems of unprecedented multifunctionality and sophistication. PMID- 27363371 TI - Artificial Organelles: Reactions inside Protein-Polymer Supramolecular Assemblies. AB - Reactions inside confined compartments at the nanoscale represent an essential step in the development of complex multifunctional systems to serve as molecular factories. In this respect, the biomimetic approach of combining biomolecules (proteins, enzymes, mimics) with synthetic membranes is an elegant way to create functional nanoreactors, or even simple artificial organelles, that function inside cells after uptake. Functionality is provided by the specificity of the biomolecule(s), whilst the synthetic compartment provides mechanical stability and robustness. The availability of a large variety of biomolecules and synthetic membranes allows the properties and functionality of these reaction spaces to be tailored and adjusted for building complex self-organized systems as the basis for molecular factories. PMID- 27363372 TI - Compartmentalization - A Prerequisite for Maintaining and Changing an Identity. AB - The chemical manipulation of DNA is much more convenient than the manipulation of the bioproducts, such as enzymes, that it encodes. The optimization of bioproducts requires cycles of diversification of DNA followed by read-out of the information into the bioproduct. Maintaining the link between the information - the genotype - and the properties of the bioproduct - the phenotype - through some form of compartmentalization is therefore an essential aspect in directed evolution. While the ideal compartment is a biological cell, many projects involving more radical changes in the bioproduct, such as the introduction of novel cofactors, may not be suitable for expression of the information in cells, and alternative in vitro methods have to be applied. Consequently, the possibility to produce simple and advanced micro compartments at high rates and to combine them with the ability to translate the information into proteins represents a unique opportunity to explore demanding enzyme engineering projects that require the evaluation of at least hundreds of thousands of enzyme variants over multiple generations. PMID- 27363373 TI - Functional Nanopores: A Solid-state Concept for Artificial Reaction Compartments and Molecular Factories. AB - On the road towards the long-term goal of the NCCR Molecular Systems Engineering to create artificial molecular factories, we aim at introducing a compartmentalization strategy based on solid-state silicon technology targeting zeptoliter reaction volumes and simultaneous electrical contact to ensembles of well-oriented molecules. This approach allows the probing of molecular building blocks under a controlled environment prior to their use in a complex molecular factory. Furthermore, these ultra-sensitive electrical conductance measurements allow molecular responses to a variety of external triggers to be used as sensing and feedback mechanisms. So far, we demonstrate the proof-of-concept by electrically contacting self-assembled mono-layers of alkane-dithiols as an established test system. Here, the molecular films are laterally constrained by a circular dielectric confinement, forming a so-called 'nanopore'. Device yields above 85% are consistently achieved down to sub-50 nm nanopore diameters. This generic platform will be extended to create distributed, cascaded reactors with individually addressable reaction sites, including interconnecting micro-fluidic channels for electrochemical communication among nanopores and sensing sites for reaction control and feedback. In this scientific outlook, we will sketch how such a solid-state nanopore concept can be used to study various aspects of molecular compounds tailored for operation in a molecular factory. PMID- 27363375 TI - Artificial Cell Research as a Field that Connects Chemical, Biological and Philosophical Questions. AB - This review article discusses the interdisciplinary nature and implications of artificial cell research. It starts from two historical theories: Ganti's chemoton model and the autopoiesis theory by Maturana and Varela. They both explain the transition from chemical molecules to biological cells. These models exemplify two different ways in which disciplines of chemistry, biology and philosophy can profit from each other. In the chemoton model, conclusions from one disciplinary approach are relevant for the other disciplines. In contrast, the autopoiesis model itself (rather than its conclusions) is transferred from one discipline to the other. The article closes by underpinning the relevance of artificial cell research for philosophy with reference to the on-going philosophical debates on emergence, biological functions and biocentrism. PMID- 27363374 TI - Surveying the Delivery Methods of CRISPR/Cas9 for ex vivo Mammalian Cell Engineering. AB - The simplicity of the CRISPR/Cas9 technology has been transformative in making targeted genome editing accessible for laboratories around the world. However, due to the sheer volume of literature generated in the past five years, determining the best format and delivery method of CRISPR/Cas9 components can be challenging. Here, we provide a brief overview of the progress that has been made in the ex vivo genome editing of mammalian cells and summarize the key advances made for improving efficiency and delivery of CRISPR/Cas9 in DNA, RNA, and protein form. In particular, we highlight the delivery of Cas9 components to human cells for advanced genome editing applications such as large gene insertion. PMID- 27363376 TI - On the Brink of Shifting Paradigms, Molecular Systems Engineering Ethics Needs to Take a Proactive Approach. AB - Molecular Systems Engineering (MSE) is a paradigm shift in both engineering and life sciences. While the field is still in its infancy the perspectives of MSE in revolutionising technology is promising. MSE will offer a wide range of applications in clinical, biotechnological and engineering fields while simultaneously posing serious questions on the ethical and societal aspects of such technology. The moral and societal aspects of MSE need systematic investigation from scientific and social perspectives. In a democratic setting, the societal outcomes of MSE's cutting-edge technology need to be consulted and influenced by society itself. For this purpose MSE needs inclusive public engagement strategies that bring together the public, ethicists, scientists and policy makers for optimum flow of information that maximizes the impact of public engagement. In this report we present an MSE consortium and its ethics framework for establishing a proactive approach in the study of the ethics of MSE technology. PMID- 27363380 TI - Conference Report The State of the Art of 3D Cell Cultures DECHEMA Conference in Freiburg on April 19-21, 2016. AB - Where are we today with 3D cell cultures as predictive, physiologically relevant model systems? Are there any successful applications, innovative developments or yawning gaps? The DECHEMA April conference assembled international experts to take a look behind the scenes and reveal relevant disease models, applications of 3D models in clinical practice and industry, predictive cell models for compound characterization and enabling technologies. PMID- 27363381 TI - A Fresh Wind is Blowing in from Asia Professor Michael Raghunath Arrives at ZHAW Waedenswil. AB - In summer 2016, Michael Raghunath from the National University of Singapore (NUS) will take over the professorship from Ursula Graf-Hausner in cell culture technology and tissue engineering at ZHAW Life Sciences and Facility Management. What are his objectives and the corresponding strategies? What challenges will he face, what will he choose to focus on? Michael Raghunath was kind enough to let us have a look behind the scenes. PMID- 27363382 TI - Incredibly Versatile Microbial Fuel Cells Innovative Ideas at HES-SO Valais Wallis for Solving Topical Problems. AB - At HES-SO Valais-Wallis, Prof. Fabian Fischer is specialized in microbial fuel cells for novel applications that meet the challenge of producing renewable energies. He and his team possess a unique expertise in bioelectric energy vector generation, phosphate extraction (CHIMIA 2015, 69, 296) and the testing of antimicrobial surfaces. Let's take a look behind the scenes of the Institute of Life Technologies in Sion. PMID- 27363384 TI - Stability of the guinea pigs personality - cognition - linkage over time. AB - In human psychological research, personality traits as well as cognitive traits are usually validated for both, their stability over time and contexts. While stability over time gives an estimate on how genetically fixated a trait can be, correlations across traits have the power to reveal linkages or trade - offs. In animals, these validations have widely been done for personality but not for cognitive traits. We tested guinea pigs in four consecutive discrimination tasks using four unique pairs of objects with two objects of the same form but different size in each pair. The same animals were tested twice each for three personality traits, i.e. boldness, aggression and sociopositive behaviour. The animals did not learn to "always choose the larger item" in the cognitive task but learned to discriminate the two objects of each stimulus pair anew, so that we did test for learning speed in four slightly different task setups. Performance over the four tasks was significantly repeatable as well as all tested personality traits. A stable linkage over time was found between sociopositive behaviour and learning performance, probably indicating an ecological relevance for a correlation between these two traits. Still, not all traits seem to be connected amongst each other, as in our case boldness and aggression are both not linked to individual learning performance. Future studies will hopefully further investigate the repeatability of various cognitive traits in several species and thus lead to a better understanding of the interdependence of personality and cognition. This will help to unravel which suites of traits facilitate individual life histories and hence improve our understanding of the emergence and maintenance of individual differences. PMID- 27363385 TI - Prenatal Testing for Adult-Onset Conditions: the Position of the National Society of Genetic Counselors. AB - Advances in genetic testing and the availability of such testing in pregnancy allows prospective parents to test their future child for adult-onset conditions. This ability raises several complex ethical issues. Prospective parents have reproductive rights to obtain information about their fetus. This information may or may not alter pregnancy management. These rights can be in conflict with the rights of the future individual, who will be denied the right to elect or decline testing. This paper highlights the complexity of these issues, details discussions that went into the National Society of Genetic Counselors (NSGC) Public Policy Task Force's development of the Prenatal testing for Adult-Onset Conditions position statement adopted in November 2014, and cites relevant literature on this topic through December 2015. Issues addressed include parental rights and autonomy, rights of the future child, the right not to know, possible adverse effects on childhood and the need for genetic counseling. This paper will serve as a reference to genetic counselors and healthcare professionals when faced with this situation in clinical practice. PMID- 27363386 TI - PSMA-Targeted 18F-DCFPyL PET/CT Imaging of Clear Cell Renal Cell Carcinoma: Results from a Rapid Autopsy. PMID- 27363387 TI - Sensitivity, Specificity, and Predictors of Positive 68Ga-Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer: A Systematic Review and Meta-analysis. AB - CONTEXT: Positron emission tomography (PET) of 68Ga-labelled prostate-specific membrane antigen (68Ga-PSMA) is an emerging imaging modality introduced to assess the burden of prostate cancer, typically in biochemically recurrent or advanced disease. 68Ga-PSMA PET provides the ability to selectively identify and localize metastatic prostate cancer cells and subsequently change patient management. Owing to its limited history, robust sensitivity and specificity data are not available for 68Ga-PSMA PET-positive scans. OBJECTIVE: A systematic review and meta-analysis of reported predictors of positive 68Ga-PSMA PET and corresponding sensitivity and specificity profiles. EVIDENCE ACQUISITION: We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Library, and Web of Science databases in April 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality was assessed using the Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analysis and meta regression of proportions were performed using a random-effects model with pre PET prostate-specific antigen (PSA) levels as the dependent variable. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models. EVIDENCE SYNTHESIS: Sixteen articles involving 1309 patients were analysed. The overall percentage of positive 68Ga-PSMA PET among patients was 40% (95% confidence interval [CI] 19-64%) for primary staging and 76% (95% CI 66-85%) for biochemical recurrence (BCR). Positive 68Ga-PSMA PET scans for BCR patients increased with pre-PET PSA. For the PSA categories 0-0.2, 0.2-1, 1-2, and >2 ng/ml, 42%, 58%, 76%, and 95% scans, respectively, were positive. Shorter PSA doubling time increased 68Ga-PSMA PET positivity. On per patient analysis, the summary sensitivity and specificity were both 86%. On per lesion analysis, the summary sensitivity and specificity were 80% and 97%, respectively. CONCLUSIONS: In the setting of BCR prostate cancer, pre-PET PSA predicts the risk of positive 68Ga-PSMA PET. Pooled data indicate favourable sensitivity and specificity profiles compared to choline-based PET imaging techniques. PATIENT SUMMARY: Positron emission tomography using 68Ga-labelled prostate-specific membrane antigen is an emerging radiological technique developed to improve the characterisation of metastatic prostate cancer. We summarised the data available to date and found that this new test provides excellent rates of detection of cancer spread in late-stage prostate cancer. PMID- 27363388 TI - Genetic mixture of multiple source populations accelerates invasive range expansion. AB - A wealth of population genetic studies have documented that many successful biological invasions stem from multiple introductions from genetically distinct source populations. Yet, mechanistic understanding of whether and how genetic mixture promotes invasiveness has lagged behind documentation that such mixture commonly occurs. We conducted a laboratory experiment to test the influence of genetic mixture on the velocity of invasive range expansion. The mechanistic basis for effects of genetic mixture could include evolutionary responses (mixed invasions may harbour greater genetic diversity and thus elevated evolutionary potential) and/or fitness advantages of between-population mating (heterosis). If driven by evolution, positive effects of source population mixture should increase through time, as selection sculpts genetic variation. If driven by heterosis, effects of mixture should peak following first reproductive contact and then dissipate. Using a laboratory model system (beetles spreading through artificial landscapes), we quantified the velocity of range expansion for invasions initiated with one, two, four or six genetic sources over six generations. Our experiment was designed to test predictions corresponding to the evolutionary and heterosis mechanisms, asking whether any effects of genetic mixture occurred in early or later generations of range expansion. We also quantified demography and dispersal for each experimental treatment, since any effects of mixture should be manifest in one or both of these traits. Over six generations, invasions with any amount of genetic mixture (two, four and six sources) spread farther than single-source invasions. Our data suggest that heterosis provided a 'catapult effect', leaving a lasting signature on range expansion even though the benefits of outcrossing were transient. Individual level trait data indicated that genetic mixture had positive effects on local demography (reduced extinction risk and enhanced population growth) during the initial stages of invasion but no consistent effects on dispersal ability. Our work is the first to demonstrate that genetic mixture can alter the course of spatial expansion, the stage of invasion typically associated with the greatest ecological and economic impacts. We suggest that similar effects of genetic mixture may be a common feature of biological invasions in nature, but that these effects can easily go undetected. PMID- 27363389 TI - BMP1-like proteinases are essential to the structure and wound healing of skin. AB - Closely related extracellular metalloproteinases bone morphogenetic protein 1 (BMP1) and mammalian Tolloid-like 1 (mTLL1) are co-expressed in various tissues and have been suggested to have overlapping roles in the biosynthetic processing of extracellular matrix components. Early lethality of mice null for the BMP1 gene Bmp1 or the mTLL1 gene Tll1 has impaired in vivo studies of these proteinases. To overcome issues of early lethality and functional redundancy we developed the novel BTKO mouse strain, with floxed Bmp1 and Tll1 alleles, for induction of postnatal, simultaneous ablation of the two genes. We previously showed these mice to have a skeletal phenotype that includes elements of osteogenesis imperfecta (OI), osteomalacia, and deficient osteocyte maturation, observations validated by the finding of BMP1 mutations in a subset of human patients with OI-like phenotypes. However, the roles of BMP1-like proteinase in non-skeletal tissues have yet to be explored, despite the supposed importance of putative substrates of these proteinases in such tissues. Here, we employ BTKO mice to investigate potential roles for these proteinases in skin. Loss of BMP1 like proteinase activity is shown to result in markedly thinned and fragile skin with unusually densely packed collagen fibrils and delayed wound healing. We demonstrate deficits in the processing of collagens I and III, decorin, biglycan, and laminin 332 in skin, which indicate mechanisms whereby BMP1-like proteinases affect the biology of this tissue. In contrast, lack of effects on collagen VII processing or deposition indicates this putative substrate to be biosynthetically processed by non-BMP1-like proteinases. PMID- 27363390 TI - A De-Novo Genome Analysis Pipeline (DeNoGAP) for large-scale comparative prokaryotic genomics studies. AB - BACKGROUND: Comparative analysis of whole genome sequence data from closely related prokaryotic species or strains is becoming an increasingly important and accessible approach for addressing both fundamental and applied biological questions. While there are number of excellent tools developed for performing this task, most scale poorly when faced with hundreds of genome sequences, and many require extensive manual curation. RESULTS: We have developed a de-novo genome analysis pipeline (DeNoGAP) for the automated, iterative and high throughput analysis of data from comparative genomics projects involving hundreds of whole genome sequences. The pipeline is designed to perform reference-assisted and de novo gene prediction, homolog protein family assignment, ortholog prediction, functional annotation, and pan-genome analysis using a range of proven tools and databases. While most existing methods scale quadratically with the number of genomes since they rely on pairwise comparisons among predicted protein sequences, DeNoGAP scales linearly since the homology assignment is based on iteratively refined hidden Markov models. This iterative clustering strategy enables DeNoGAP to handle a very large number of genomes using minimal computational resources. Moreover, the modular structure of the pipeline permits easy updates as new analysis programs become available. CONCLUSION: DeNoGAP integrates bioinformatics tools and databases for comparative analysis of a large number of genomes. The pipeline offers tools and algorithms for annotation and analysis of completed and draft genome sequences. The pipeline is developed using Perl, BioPerl and SQLite on Ubuntu Linux version 12.04 LTS. Currently, the software package accompanies script for automated installation of necessary external programs on Ubuntu Linux; however, the pipeline should be also compatible with other Linux and Unix systems after necessary external programs are installed. DeNoGAP is freely available at https://sourceforge.net/projects/denogap/ . PMID- 27363392 TI - We need better medical undergraduate education in Ecuador. The case of perinatal mortality. PMID- 27363391 TI - Abrogating ClC-3 Inhibits LPS-induced Inflammation via Blocking the TLR4/NF kappaB Pathway. AB - This study investigated the function of a chloride channel blocker, DIDS. Both in vitro and in vivo studies found that DIDS significantly inhibits lipopolysaccharide (LPS)-induced release of proin flammatory cytokines. Here, we show that DIDS inhibits LPS-induced inflammation, as shown by downregulation of inflammatory cytokines via inhibition of the TLR4/NF-kappaB pathway. Furthermore, we show that ClC-3siRNA transfection reduces LPS-induced pro-inflammation in Raw264.7 cells, indicating that ClC-3 is involved in the inhibitory effect of DIDS during LPS-induced cytokines release. In vivo, DIDS reduced LPS-induced mortality, decreased LPS-induced organic damage, and down-regulated LPS-induced expression of inflammatory cytokines. In sum, we demonstrate that ClC-3 is a pro inflammatory factor and that inhibition of ClC-3 inhibits inflammatory induction both in vitro and in vivo, suggesting that ClC-3 is a potential anti-inflammatory target. PMID- 27363393 TI - [Psychometric validation in Spanish of the Brazilian short version of the Primary Care Assessment Tools-users questionnaire for the evaluation of the orientation of health systems towards primary care]. AB - OBJECTIVE: To validate the Brazilian short version of the PCAT for adult patients in Spanish. DESIGN: Analysis of secondary data from studies made to validate the extended version of the PCAT questionnaire. LOCATION: City of Cordoba, Argentina. Primary health care. PARTICIPANTS: The sample consisted of 46% of parents, whose children were enrolled in secondary education in three institutes in the city of Cordoba, and the remaining 54% were adult users of the National University of Cordoba Health Insurance. MAIN MEASURES: Pearson's correlation coefficient comparing the extended and short versions. Goodness-of-fit indices in confirmatory factor analysis, composite reliability, average variance extracted, and Cronbach's alpha values, in order to assess the construct validity and the reliability of the short version. RESULTS: The values of Pearson's correlation coefficient between this short version and the long version were high .818 (P<.001), implying a very good criterion validity. The indicators of good global adjustment to the confirmatory factor analysis were good. The value of composite reliability was good (.802), but under the variance media extracted: .3306, since 3 variables had weak factorials loads. The Cronbach's alpha was acceptable (.85). CONCLUSIONS: The short version of the PCAT-users developed in Brazil showed an acceptable psychometric performance in Spanish as a quick assessment tool, in a comparative study with the extended version. PMID- 27363394 TI - [Risk factors and burnout levels in Primary Care nurses: A systematic review]. AB - OBJECTIVE: To determine the risk factors and levels of burnout in Primary Care nurses. METHODS: A systematic review was performed. DATA SOURCES: CINAHL, CUIDEN, LILACS, PubMed, ProQuest, ScienceDirect and Scopus databases were consulted. Search equations were 'burnout AND community health nursing' and 'burnout AND primary care nursing'. The search was performed in October 2015. STUDY SELECTION: The final sample was n=12 studies. Quantitative primary studies that used Maslach Burnout Inventory for burnout assessment in Primary Care nurses were included without restriction by publication date. DATA EXTRACTION: The main variables were the mean and standard deviation of the three burnout dimensions, high, medium and low prevalence rates of each dimension, and socio-demographic, occupational and psychological variables that potentially influence burnout level. RESULTS: Studies show high prevalence rates, generally between 23% and 31%, of emotional exhaustion. The prevalence rates of high depersonalisation and low personal accomplishment show heterogeneity, varying between 8%-32% and 4%-92% of the sample, respectively. Studies show that older nurses with more seniority, anxiety and depression, among other variables, have higher burnout levels, while nurses with higher salary, high job satisfaction, organisational support, and good self concept have less burnout. CONCLUSION: High emotional exhaustion is the main affected dimension of burnout in Primary Care nursing. There is heterogeneity in depersonalisation and personal accomplishment. Burnout must be prevented in these professionals, by increasing protective factors and monitoring its appearance in those with risk factors. PMID- 27363395 TI - The Predictive Power of Serum alpha-Fetoprotein and Des-gamma-Carboxy Prothrombin for Survival Varies by Tumor Size in Hepatocellular Carcinoma. AB - Alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) are frequently used as tumor markers in hepatocellular carcinoma (HCC). The authors hypothesized different patient populations with varying tumor sizes would influence the predictive power of tumor markers for survival in HCC patients. The authors investigated the influence of tumor size on predictive powers of AFP and DCP. 181 patients underwent hepatectomy for HCC from 2003 to 2008 at Kobe University Hospital. Tumor markers were measured before and at 1 month post-hepatectomy. The Cox proportional-hazards model revealed that preoperative serum AFP was associated with survival; its effects depended on tumor size. Hazard ratios (HRs) for preoperative AFP were maximum for medium-sized HCC, and for DCP, HRs were maximum in small-sized tumors. Post-hepatectomy, both tumor markers were associated with survival, revealing significant interactions with tumor size. HRs for postoperative AFP were greater than 1 for relatively wide range tumors (3-11 cm). HRs for postoperative DCP increased with tumor size, with a strong prognostic predictive power for tumors >5 cm. The predictive power of serum tumor markers varied by tumor size in HCC patients. By selecting the appropriate tumor marker, its predictive power can be improved. PMID- 27363396 TI - Shakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang) as Treatment of Painful Muscle Cramps in Patients with Lumbar Spinal Stenosis and Its Minimum Effective Dose. AB - Shakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang) is a Kampo medicine, which is known to be effective against muscle cramps as well as crampy pain in the gastrointestinal smooth muscle and skeletal muscle. However, glycyrrhizin in this medicine also causes adverse drug reactions such as hypokalemia, hypertension, and edema. We analyzed the therapeutic efficacy of Shakuyaku-kanzo-to for painful muscle cramps associated with lumbar spinal stenosis and clarified its minimum effective dose. 58 patients with lumbar spinal stenosis and painful muscle cramps were included. We evaluated the therapeutic efficacy of Shakuyaku-kanzo-to (n=16) comparing with eperisone hydrochloride (n=14). We then examined the minimum effective dose of Shakuyaku-kanzo-to in the remaining 28 patients. Shakuyaku-kanzo-to reduced the frequency of painful muscle cramps to less than 50% in 13 of 16 patients. However, eperisone hydrochloride reduced it to the same level in 4 of 14 patients. The onset of the maximum therapeutic effect of Shakuyaku-kanzo-to was less than 3 days from the start of treatment in 11 of 15 patients. Regarding the minimum effective dose for painful muscle cramps, 2.5 g of Shakuyaku-kanzo-to used as needed had a therapeutic effect that was equivalent to the regular use of 7.5 g/day (given in divided doses three times daily). Our data show that Shakuyaku-kanzo-to is effective for painful muscle cramps associated with lumbar spinal stenosis. The dosage of 2.5 g of Shakuyaku-kanzo-to as needed had a therapeutic effect that was equal to the regular use of 7.5 g/day. PMID- 27363397 TI - Differentiation between Viable and Dead Cryptosporidium Oocysts Using Fluorochrome Staining. AB - The use of nucleic acid staining with a fluorochrome dye to differentiate viable and dead (heat-killed) Cryptosporidium oocysts was assessed. The specificities (percentage of unstained viable oocysts) and sensitivities (percentage of stained dead oocysts) of the seven tested dyes (SYTO-17(r) and SYTO-59(r) to 64(r)) ranged from 65 to 76% (average 71%) and 83 to 95% (average 91%), respectively. SYTO-59 and SYTO-17 imparted greater color (4+) intensity than the other dyes (2+ or less). Of these two dyes, SYTO-17 exhibited more brightness and slower discoloration and was selected for use in further experiments. The optimum staining time for SYTO-17 at 37C was one hour or more (sensitivity of 96%). Dye concentrations of 20 and 30 uM resulted in maximal color intensity, and no further improvement was observed with further increases in dye concentration. Staining a mixture of viable and dead oocysts (1:1 ratio) with 20 uM dye at 37C for one hour yielded the expected results (approximately 50%), but no remarkable increase in the percent staining with time (up to 8 hours) was observed. In this study, no ghost oocysts were observed. The present study indicated that the fluorogenic nucleic acid dye SYTO-17 could be used to discriminate between live and dead Cryptosporidium oocysts. PMID- 27363398 TI - Effects of Levodopa on Vowel Articulation in Patients with Parkinson's Disease. AB - OBJECTIVES: The effects of levodopa on articulatory dysfunction in patients with Parkinson's disease remain inconclusive. This study aimed to investigate the effects of levodopa on isolated vowel articulation and motor performance in patients with moderate to severe Parkinson's disease, excluding speech fluctuations caused by dyskinesia. METHODS: 21 patients (14 males and 7 females) and 21 age- and sex- matched healthy subjects were enrolled. Together with motor assessment, the patients phonated five Japanese isolated vowels (/a/, /i/, /u/, /e/, and /o/) 20 times before and 1 h after levodopa treatment. We made the frequency analysis of each vowel and measured the first and second formants. From these formants we constructed the pentagonal vowel space area which should be the good indicator for articulatory dysfunction of vowels. In control subjects, only speech samples were analyzed. To investigate the sequential relationship between plasma levodopa concentrations, motor performances, and acoustic measurements after treatment, entire drug cycle tests were performed in 4 patients. RESULTS: The pentagonal vowel space area was significantly expanded together with motor amelioration after levodopa treatment, although the enlargement is not enough for the space area of control subjects. Drug cycle tests revealed that sequential increases or decreases in plasma levodopa levels after treatment correlated well with expansion or decrease of the vowel space areas and improvement or deterioration of motor manifestations. CONCLUSIONS: Levodopa expanded the vowel space area and ameliorated motor performance, suggesting that dysfunctions in vowel articulation and motor performance in patients with Parkinson's disease are based on dopaminergic pathology. PMID- 27363399 TI - Identification of fetal cardiac anatomy and hemodynamics: a novel enhanced screening protocol. AB - BACKGROUND: Prenatal cardiac screening is of great importance as it contributes to appropriate neonatal management and helps parents to make a decision regarding their pregnancy. The aim of our study was to evaluate the efficiency of a newly proposed screening protocol in the detection of fetal congenital heart disease (CHD). METHODS: This was a prospective study. A total of 52 cases of confirmed CHD fetuses and 248 cases of randomly selected normal fetuses were included in the study. Two sonographers with similar experience performed the cardiac screenings under two different protocols independently. The conventional protocol (Protocol A) paid greater attention to the four-chamber view and the outflow tract views. A 6-month training program was provided to sonographers performing scans under the new protocol (Protocol B), which emphasized systematically evaluating fetal cardiac anatomy and hemodynamics. Color Doppler was mandatory and some ultrasonic signs for special cardiac anomalies were also introduced into this protocol. RESULTS: Protocol B detected more cardiac anomalies than did Protocol A (96.2 % vs. 61.5 %, P < 0.01). Specifically, Protocol B was superior to Protocol A in detecting cardiac malpositions, abnormal systemic and pulmonary venous connection, right aortic arch, transposition of the great arteries, and congenital corrected transposition of the great arteries. By visualizing flow disturbance and retrograde flow with color Doppler, Protocol B was better than Protocol A in screening valvular associated malformations, such as pulmonary atresia, pulmonary stenosis, tricuspid dysplasia, etc. For the normal fetuses, Protocol B was better than Protocol A in reducing the false-positive detection of septal defects. CONCLUSIONS: The current study introduces an enhanced protocol for fetal cardiac screening, under which the obstetric screening sonographers systematically identify fetal cardiac anatomy and hemodynamics. A short-term training program makes it possible for the screening sonographers to become familiar with the new protocol, and its value has been confirmed due to improvements made in screening efficiency. PMID- 27363400 TI - Patient-activation and guideline-concordant pharmacological treatment after bone density testing: the PAADRN randomized controlled trial. AB - : Patients often do not know or understand their bone density test results, and pharmacological treatment rates are low. In a clinical trial of 7749 patients, we used a tailored patient-activation result letter accompanied by a bone health brochure to improve appropriate pharmacological treatment. Treatment rates, however, did not improve. INTRODUCTION: Patients often do not know or understand their dual-energy x-ray absorptiometry (DXA) test results, which may lead to suboptimal care. We tested whether usual care augmented by a tailored patient activation DXA result letter accompanied by an educational brochure would improve guideline-concordant pharmacological treatment compared to usual care only. METHODS: We conducted a randomized, controlled, double-blinded, pragmatic clinical trial at three health care centers in the USA. We randomized 7749 patients >=50 years old and presenting for DXA between February 2012 and August 2014. The primary clinical endpoint at 12 and 52 weeks post-DXA was receiving guideline-concordant pharmacological treatment. We also examined four of the steps along the pathway from DXA testing to that clinical endpoint, including (1) receiving and (2) understanding their DXA results and (3) having subsequent contact with their provider and (4) discussing their results and options. RESULTS: Mean age was 66.6 years, 83.8 % were women, and 75.3 % were non-Hispanic whites. Intention-to-treat analyses revealed that guideline-concordant pharmacological treatment was not improved at either 12 weeks (65.1 vs. 64.3 %, p = 0.506) or 52 weeks (65.2 vs. 63.8 %, p = 0.250) post-DXA, even though patients in the intervention group were more likely (all p < 0.001) to recall receiving their DXA results letter at 12 weeks, correctly identify their results at 12 and 52 weeks, have contact with their provider at 52 weeks, and have discussed their results with their provider at 12 and 52 weeks. CONCLUSION: A tailored DXA result letter and educational brochure failed to improve guideline-concordant care in patients who received DXA. PMID- 27363401 TI - Visit-to-visit variation of fasting plasma glucose is a predictor of hip fracture in older persons with type 2 diabetes: the Taiwan Diabetes Study. AB - : We investigated the association between fasting plasma glucose variability (FPG CV) and the risk of hip fracture in elderly diabetic patients. Our finding showed a temporal association between FPG-CV and hip fracture as patients categorized as FPG-CV greater than 25.4 % showed an increased risk in hip fractures. INTRODUCTION: Hip fracture is a major health burden in the population and is associated with high rates of mortality and morbidity especially in elderly. It is evident that diabetes mellitus is a risk factor of osteoporosis which is a significant risk factor of hip fracture. However, epidemiological studies exploring the risks of hip fracture among type 2 diabetic patients are limited. METHODS: A retrospective study of 26,501 ethnic Chinese older persons enrolled in the National Diabetes Care Management program in Taiwan was conducted; related factors were analyzed with extended Cox proportional hazards regression models to competing risk data on hip fracture incidence. RESULTS: The results show a temporal association between FPG-CV and hip fracture as patients categorized as FPG-CV greater than 25.4 % showed an increased risk in hip fractures, confirming a linear relationship between the two. After multivariate adjustment, the risk of hip fracture increased among patients with FPG-CV of 25.4-42.3 % and >42.3 % compared with patients with FPG-CV of ? 14.3 % (hazard ratio, 1.35; 95 % confidence interval 1.14-1.60 and 1.27; 1.07-1.52, respectively). Significant linear trends among various FPG-CV were observed. CONCLUSIONS: Thus, the present study demonstrated the importance of glucose stability for fracture prevention in older persons with type 2 diabetes. Future studies should be conducted to explore whether reduction in glucose oscillation in older adults with diabetes mellitus can reduce the risk of hip fracture. PMID- 27363402 TI - Squamous cell carcinoma of unknown primary tumor metastatic to neck nodes: role of elective irradiation. AB - In patients with squamous cell carcinoma (SCC) metastases to neck lymph nodes and unknown primary tumor, the role of elective irradiation of uninvolved neck and potential mucosal primary sites is yet to be determined. The aim of this study was to review the experience treating SCC of unknown primary metastatic to neck nodes with surgery and postoperative radiotherapy (PORT) in Slovenia between 1995 and 2010 and to determine the importance of the extent of irradiated volume. For this purpose, the nationwide Cancer Registry of Slovenia database was used for identifying patients. 126 patients were identified. Involved-field PORT and extended-field PORT was used in 50 and 76 patients, respectively. At 5 years, locoregional control was 86 %, disease-specific survival 77 %, and overall survival 57 %. In multivariate analysis, the extent of irradiated volume has not been predictive for any outcome under study. Grade >=3 acute and late radiotherapy-induced toxicities were more frequent in the extended-field PORT group. In conclusion, although not superior, involved-field PORT seems to be a preferred treatment option in SCC of unknown primary metastatic to neck nodes due to significantly reduced toxicity and better prospects for successful salvage. PMID- 27363403 TI - The senile functional evolution of the larynx after supracricoid reconstructive surgery. AB - Supracricoid partial laryngectomy is a relevant organ-preserving surgical technique used for the treatment of early or locally advanced laryngeal tumors with an oncologic outcome comparable with that of total laryngectomy. This reconstructive surgery is certainly technically feasible also in the elderly, but the problem is postoperatively as the patient may lack the will and strength to be successfully rehabilitated. The goal was to evaluate functional outcomes, in a maximum follow-up period of ten years from the end of the postoperative follow up, in a cohort of elderly patients to look at the senile evolution of the laryngeal post surgical function comparing the amount of resection and grade of possible impairment of swallowing and phonatory parameters. A group of 33 patients were selected for a retrospective study aimed at evaluating the long term evolution of laryngeal functionality after surgery, with the baseline at 5 years from the end of follow-up. All the patients had three-monthly visits for a period up to ten years, during which the objective and subjective swallowing and phonatory parameters were recorded, analyzed and, at the end of the study, compared with baseline. The results suggest that long-term post surgical functional problems may develop also in the neolarynx where the effects of the reconstructive surgery, on speech and swallowing, are largely stabilized. The presence of arytenoid resection had significantly impacted on the occurrence of aspiration even if the overall number of dysphagic patients was not statistically significant compared to baseline. PMID- 27363404 TI - Comparison of endoscopic and external resections for sinonasal instestinal-type adenocarcinoma. AB - Endoscopic sinus surgery (ESS) is considered as a valid option in the management of nasal adenocarcinoma (ADC). Comparative studies with open approaches are still required. A monocentric retrospective study was carried out from May 2002 to December 2013, including 43 patients with intestinal-type adenocarcinoma of the ethmoid sinus. Non-resectable tumours or recurrences were excluded. Before 2008, open approach with lateral rhinotomy (LR) was performed as the gold standard of treatment. From 2008, ESS was systematically used as a first-line option as long as a complete resection was achievable. Adjuvant radiation therapy was delivered (RT) for all the patients. LR and ESS were performed in, respectively, 23 and 20 patients. The two groups were comparable in terms of age, occupational dust exposure, histopathological subtypes, and T stage based on the pathological assessment of the specimen (10 pT2, 26 pT3, 2 pT4a, and 5 pT4b). The tumour origin was mainly located in the olfactory cleft with the involvement of the cribriform plate in 60 % of patients. No major complication was observed in ESS group with a reduced hospital stay (5.6 vs 7.6 days). The disease-free survival was not different between LR and ESS groups over a mean follow-up period of 6.6 years. Even for local advanced stages with skull base involvement, we confirm the reliability and the advantages of ESS in terms of oncological outcomes and morbidity. We advocate complete excision of the olfactory cleft to ensure an appropriate control of the tumoral origin. PMID- 27363405 TI - Postdeglutitive residue in vagus nerve paralysis and its association with feeding style. AB - The objective of this study is to compare the postdeglutitive pharyngeal residues between Xth cranial nerve paralysis (XNP) and isolated recurrent laryngeal nerve paralysis (RLNP) to elucidate the association with feeding style. This study enrolled 15 XNP patients with injuries at the brainstem level (Group I) and 26 patients with RLNP (Group II). All subjects underwent videofluoroscopic swallowing studies (VFSS). The pyriform sinus (PS) and vallecula residues were quantified. The symmetry of the affected versus non-affected sides was compared in both groups. Feeding style at the time of VFSS was also examined. The intra rater correlation coefficients for all of the data, including the areas of both the vallecula and pyriform sinus on the affected and non-affected sides, were 0.88-0.92 (p < 0.001), reflecting high consistency of the evaluation. In Group I, there was significantly (p < 0.01) more residue in the PS, but not vallecula, compared to the respective non-affected sides, while in Group II there were no significant differences in residue between the affected and non-affected sides for either the vallecula or PS. Comparing Groups I and II, there was significant (p < 0.01) residue on the affected side in the PS but not the vallecula. There was a significant correlation between dependency on a feeding tube and XNP (p < 0.01, Chi-square test). XNP at the brainstem level may cause significantly increased residue in the PS compared to RLNP. This might increase the dependency on a feeding tube with XNP. PMID- 27363406 TI - Evaluation of the application of rhino-septal splints in endoscopic transsphenoidal skull base surgery. AB - The endoscopic transnasal route for the surgical removal of tumors in the sellar region is frequently associated with nasal complications such as synechiae or impaired nasal breathing. In this study, we investigated the impact of septal splints on avoiding surgery-related co-morbidities. 49 patients in whom endoscopic transnasal, transsphenoidal surgery for sellar tumors was performed between 2012 and 2014 were studied. In 30 of these, nasal septal splints were applied at the end of surgery to both sides of the septum and left in situ for 10 days (group 1), 19 patients received no splints (group 2). A standardized postsurgical follow-up investigation with endoscopic nasal examination, rhinomanometry and olfactory testing was performed on average 2 months postoperatively. Patients' subjective nose-related discomfort at follow-up was assessed descriptively using a set of standardized self-rating statements on nasal problems. Synechias occurred less likely with nasal septal splints (n = 15; 50 %) than without (n = 16; 84.2 %). Moreover, multiple synechiae were predominantly observed in the group without septal splints (n = 10 vs. n = 2). Rhinomanometry showed improved flow-V150-inspiration scores when splints were used (with significant differences between groups for the left nostril: p = 0.039 and p = 0.022, resp.). In accordance, impaired nasal breathing after surgery was reported more frequently by 76.9 % of patients without splints, but only 56 % of patients with splints. Our results provide support for the application of nasal septal splints when operating endoscopically on tumors in the sellar region to reduce postoperative synechias and to improve nasal breathing. PMID- 27363407 TI - Effects of triamcinolone-impregnated nasal dressing on subjective and objective outcomes following endoscopic sinus surgery. AB - The aim of this study was to compare the effects of triamcinolone (TA)- and saline-soaked biodegradable nasal dressing on subjective symptoms, wound healing and improvement of olfactory dysfunction in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) after undergoing endoscopic sinus surgery (ESS). The study was a prospective, randomized, double-blinded, placebo-controlled study. A total of 80 patients undergoing bilateral ESS for CRSwNP were enrolled and randomly assigned to two groups. Nasal dressing was impregnated with normal saline in the control group, while patients received triamcinolone-impregnated dressing in the TA group. Sino-Nasal Outcome Test 20 (SNOT-20) and Korean Version of the Sniffin' Stick (KVSS) II test were used to assess the patients' condition preoperatively and at postoperative 1 and 3 months. Lund-Kennedy (L-K) and perioperative sinus endoscopy (POSE) scores were assessed on postoperative months 1, 2, and 3. There were significant differences between the control group and the TA group in terms of postoperative L-K scores and POSE scores at 1 and 2 months. The postoperative endoscopic scores were significantly decreased in the TA group compared to the control at 1 month. Olfactory functions were significantly improved at postoperative 3 months (p = 0.0099) compared to the preoperative score in the TA group. Significant improvement in the olfactory functions among anosmic and hyposmic patients at postoperative 1 month (p = 0.0475) and 3 months (p = 0.0019) compared to their preoperative olfactory function score was observed only in the TA group. TA-impregnated dressing had a significant advantage over saline-soaked dressing with regard to postoperative wound healing and improvement of olfactory function. PMID- 27363408 TI - Long-term effects of parotidectomy. AB - The present study investigated the long-term complications of parotidectomy, the differences in these complications in regard to the pathological diagnosis and type of surgery. The patients were questioned regarding the presence of facial paresis-paralysis, pain, loss of sensation, scarring, collapse, and mouth dryness in the area of operation. Complaints of pain (p = 0.287), scarring (p = 0.456), and mouth dryness (p = 0.136) did not show statistically significant differences between the cases with benign or malignant pathological outcomes. However, complaints of loss of sensation (p < 0.001), collapse in the area of operation (p = 0.025), paresis-paralysis (p < 0.001), and fear of repeated surgery (p = 0.032) were present at significantly higher rates. Complaints of pain (p = 0.258), scarring (p = 0.665), mouth dryness (p = 0.113) and fear of repeated surgery (p = 0.053) did not show statistically significant differences between the cases who underwent superficial or total parotidectomy. However, complaints of loss of sensation (p = 0.002), paresis (p < 0.001), and collapse in the area of operation (p = 0.019) were present at significantly higher rates. The type of tumor and surgical approach significantly affect the quality of life; however, parotidectomy generally does not lead to serious long-term complications that would disturb the patients. PMID- 27363409 TI - Estimation of cardiovascular disease from polysomnographic parameters in sleep disordered breathing. AB - We aimed to illustrate the causal relationships between cardiovascular diseases (CVDs) and various polysomnographic variables, and to develop a CVD estimation model from these variables in a population referred for assessment of possible sleep-disordered breathing (SDB). Clinical and polysomnographic data of 1162 consecutive patients with suspected SDB whose comorbidity status was known, were reviewed, retrospectively. Variable selection was performed in two steps using univariate analysis and tenfold cross validation information gain analysis. The resulting set of variables with an average merit value (m) of >0.005 was considered to be causal factors contributing to the CVDs, and used in Bayesian network models for providing estimations. Of the 1162 patients, 234 had CVDs (20.1 %). In total, 28 parameters were evaluated for variable selection. Of those, 19 were found to be associated with CVDs. Age was the most effective attribute in estimating CVD (m = 0.051), followed by total sleep time with oxygen saturation <90 % (m = 0.021). Some other important variables were apnea-hypopnea index during non-rapid eye movement (m = 0.018), lowest oxygen saturation (m = 0.018), body mass index (m = 0.016), total apnea duration (m = 0.014), mean apnea duration (m = 0.014), longest apnea duration (m = 0.013), and severity of SDB (m = 0.012). The modeling process resulted in a final model, with 76.9 % sensitivity, 96.2 % specificity, and 92.6 % negative predictive value, consisting of all selected variables. The study provides evidence that the estimation of CVDs from polysomnographic parameters is possible with high predictive performance using Bayesian network analysis. PMID- 27363411 TI - Functional Profiles of Human Umbilical Cord-Derived Adult Mesenchymal Stem Cells in Obese/Diabetic Versus Healthy Women. AB - BACKGROUND: Adult human mesenchymal stem cells retrieved, from the post-partum human umbilical cord Wharton jelly (hUCMS), have recently gained growing interest due to their morphological and functional properties. OBJECTIVE: The main purpose of our work was to examine morphology and functional properties of hUCMS retrieved from healthy women as compared to those with obesity, or gestational or type 2 diabetes mellitus, under fair metabolic control. Possible differences between groups could shed light into the potential use of these cells for the cell therapy of a variety of diseases, regardless of the obesity/diabetes status of the donor mothers. Additionally, information on how the maternal disease may affect the cord-derived stem cells, hence possibly newborn children would be important. METHOD: We have studied obese/diabetic or normal donor post-partum umbilical cord-derived hUCMS, either in basal or during differentiation protocols into several cell phenotypes and the definitive endoderm. Immunomodulatory properties of these cells, in terms of inhibition of activated lymphocyte proliferation, also was examined. RESULTS: According to our preliminary results, there are functional differences, as assessed by cell and molecular assays, in terms of both, differentiation and immunomodulatory potential, between the cells derived from normal as compared to obese/diabetic mothers. CONCLUSION: The findings seemingly indicate that the uterine environment of obese/diabetic mothers is quite distant from normal, regardless of metabolic control. Hence hUCMS extracted from obese/diabetic mothers do not appear to be suitable for cell therapy clinical protocols but more studies are required. PMID- 27363412 TI - Stem-cell-based Therapies for Improving Islet Transplantation Outcomes in Type 1 Diabetes. AB - INTRODUCTION: Beta-cell replacement by human islets or whole pancreas offers a life-saving therapeutic remedy for patients suffering from type 1 diabetes, providing considerable advantages with respect to diminishing total daily insulin dose and lowering frequencies of debilitating hypoglycemic reactions as well as preventing chronic micro- and macrovascular complications. Although remarkable progress has been made in this area, several hurdles remain, hampering its wide spread applicability. Such hurdles include a limiting supply of islets, the necessity of several donors to achieve enough islet mass for insulin independence, and graft failure because of metabolic pressure, continued autoimmunity, alloimmunity, high concentrations of immunosuppressive drugs as well as oxidative stress caused by hypoxia or inflammation. On the other hand, the islet transplant procedure provides the possibility to undertake multiple practical and beneficial manipulations of the beta cells before engraftment with the intention to reach improved graft survival results. CONCLUSION: We have focused on the current status of various obstacles in islet transplantation and on the potential of (stem)cell-based treatments able to stimulate islet graft outcome in pre-clinical and clinical transplantation settings in which specific attention is given to the engraftment-enhancing and immunomodulatory potential of various types of stem cells.. PMID- 27363415 TI - Occurrence of dead core in catalytic particles containing immobilized enzymes: analysis for the Michaelis-Menten kinetics and assessment of numerical methods. AB - In this article, the occurrence of dead core in catalytic particles containing immobilized enzymes is analyzed for the Michaelis-Menten kinetics. An assessment of numerical methods is performed to solve the boundary value problem generated by the mathematical modeling of diffusion and reaction processes under steady state and isothermal conditions. Two classes of numerical methods were employed: shooting and collocation. The shooting method used the ode function from Scilab software. The collocation methods included: that implemented by the bvode function of Scilab, the orthogonal collocation, and the orthogonal collocation on finite elements. The methods were validated for simplified forms of the Michaelis Menten equation (zero-order and first-order kinetics), for which analytical solutions are available. Among the methods covered in this article, the orthogonal collocation on finite elements proved to be the most robust and efficient method to solve the boundary value problem concerning Michaelis-Menten kinetics. For this enzyme kinetics, it was found that the dead core can occur when verified certain conditions of diffusion-reaction within the catalytic particle. The application of the concepts and methods presented in this study will allow for a more generalized analysis and more accurate designs of heterogeneous enzymatic reactors. PMID- 27363413 TI - Excessive daytime sleepiness is associated with an exacerbation of migraine: A population-based study. AB - BACKGROUND: Previous studies have shown that migraine and sleep disturbances are closely associated. Excessive daytime sleepiness (EDS) is a common symptom of various types of sleep disturbance. Findings from clinic-based studies suggest that a high percentage of migraineurs experience EDS. However, the prevalence and clinical impact of EDS among migraineurs at the population level have rarely been reported. The objective of this study was to investigate the prevalence and impact of EDS among migraineurs using a population-based sample in Korea. METHODS: We selected a stratified random sample of Koreans aged 19 to 69 years and evaluated them using a semi-structured interview designed to identify EDS, headache type, and the clinical characteristics of migraine. If the score on the Epworth Sleepiness Scale (ESS) was more than or equal to 11, the participant was classified as having EDS. RESULTS: Of the 2,695 participants that completed the interview, 143 (5.3 %) and 313 (11.6 %) were classified as having migraine and EDS, respectively. The prevalence of EDS was significantly higher in participants with migraine (19.6 %) and non-migraine headache (13.4 %) compared to non headache controls (9.4 %). Migraineurs with EDS had higher scores on the Visual Analogue Scale (VAS) for headache intensity (6.9 +/- 1.8 vs. 6.0 +/- 1.9, p = 0.014) and Headache Impact Test-6 (59.8 +/- 10.2 vs. 52.5 +/- 8.2, p < 0.001) compared to migraineurs without EDS. CONCLUSIONS: Approximately 20 % of migraineurs had EDS in this population-based sample. Excessive daytime sleepiness was associated with an exacerbation of some migraine symptoms. PMID- 27363414 TI - Framing visual roll-motion affects postural sway and the subjective visual vertical. AB - Effects of visual roll-motion on postural sway and the subjective visual vertical (SVV) often is studied using mechanical devices, whereas electronic displays offer cheaper and more flexible alternatives. These devices typically emit and reflect light scattered by the edges of the screen, providing Earth-fixed cues of verticality. These cues may decrease the effects of rotating stimuli, a possibility that has not been studied explicitly before in one experimental design. We exposed 16 participants to a visual dot pattern, either stationary, or rotating in roll, that was or was not surrounded by a visible Earth-fixed reference frame. To eliminate unintended visual cues, the experiment was performed in complete darkness and participants wore neutral density goggles passing only 1% of light. Postural sway was measured using a force platform. SVV measurements were obtained from a visible rod. To monitor the participants, motion sickness severity was obtained with an 11-point rating scale. Results showed that the presence of an Earth-fixed frame significantly decreased the effect of the rotating pattern on postural sway and SVV deviations. Therefore, when studying subjective verticality related effects of visual stimuli, it is imperative that all visual Earth-fixed cues are not just minimized but completely eliminated. The observation that an Earth-fixed frame significantly decreased the effect of the rotating pattern on both postural sway and the SVV points towards a common neural origin, possibly involving a neural representation of verticality. Finally, we showed that an electronic screen can yield similar effect sizes as those taken from the literature using mechanical devices. PMID- 27363416 TI - Evaluating the Potential for Delivery of Irinotecan via the Buccal Route: Physicochemical Characterization and In Vitro Permeation Assessment Across Porcine Buccal Mucosa. AB - Irinotecan (CPT-11) is used to treat advanced colorectal cancer as an intravenous therapy. Depending on pH, CPT-11 exists in either a lactone (active) or carboxylate (inactive) form, or both. In this investigation, the feasibility for systemic delivery of CPT-11 through the buccal route was evaluated. Permeation of CPT-11 across porcine buccal mucosa was studied in vitro using side-by-side flow through diffusion cells at 37 degrees C. Experiments were performed over a pH range from 4 to 9, and the permeability of both the lactone and carboxylate forms of CPT-11 was measured. CPT-11 steady state flux was determined over a range of donor concentrations at pH 4 (0.5, 1, 5, 10, 15, 20 mg/ml) and pH 6.8 (0.5, 5, 10 mg/ml). Steady state flux increased linearly with increasing donor concentration of CPT-11 at pH 4 (r 2 = 0.9935) and at pH 6.8 (r 2 = 0.9886). CPT-11 permeability was independent of pH, although the distribution coefficient increased with increasing pH. Estimates of permeability for the lactone and carboxylate forms were 4.16 * 10-5 cm/s and 2.6 * 10-5 cm/s, respectively. These calculated permeability values were in agreement with the in vitro experimental data. Overall, CPT-11 was found to permeate through porcine buccal mucosa via passive diffusion. CPT-11 permeability was independent of pH, suggesting that the compound was transported mainly via a paracellular route. Overall, the results of this research suggest that the buccal route is a potential extravascular mode of delivery for CPT-11. PMID- 27363417 TI - Timing and long-term prognosis of recurrent MI after primary angioplasty : Stent thrombosis vs. non-stent-related reinfarction. AB - BACKGROUND: In patients recovering from an ST-segment elevation myocardial infarction (STEMI), it is not clear whether the negative impact of stent thrombosis (ST) is different from a non-stent-related recurrent myocardial infarction (NSRMI). This study sought to assess the long-term incidence and prognostic impact of recurrent myocardial infarction (MI) after percutaneous coronary intervention (PCI) for STEMI by comparing outcomes of ST versus NSRMI. PATIENTS AND METHODS: From 2001 to 2007, 1025 patients undergoing PCI for STEMI were prospectively followed up. Patients with ST, with NSRMI, and those free from recurrent MI were compared regarding mortality and major adverse cardiac and cerebrovascular events (MACCE). RESULTS: Recurrent MI decreased from 37 events per 1000 person/months in the first month to 3.3 events per 1000 person/months after the first year. The cumulative 5-year incidence of ST and NSRMI was 5.27 % and 13.2 %, respectively. MACCE at 60 months after recurrence were not significantly different for patients with reinfarction but were significantly higher than for patients free from any recurrent MI (both log-rank p < 0.001). However, the cumulative all-cause death rate did not differ between the three groups (27.8 vs. 26.7 vs. 23.0 %). Compared with ST occurring in the first 30 days after PCI for STEMI, early NSRMI was associated with a significantly reduced risk for all-cause death (HR, 0.21; 95 % CI, 0.33-3.30) but this association did not persist for recurrent MIs occurring in the late (HR, 1.05; 95 % CI, 0.33 3.30) or very late follow-up periods. CONCLUSION: Although ST was associated with a significant increase in adverse events in the early recovery period, in the long term, MACCE and all-cause mortality rates were comparable to those for NSRMI. PMID- 27363410 TI - Novel concepts on pregnancy clocks and alarms: redundancy and synergy in human parturition. AB - The signals and mechanisms that synchronize the timing of human parturition remain a mystery and a better understanding of these processes is essential to avert adverse pregnancy outcomes. Although our insights into human labor initiation have been informed by studies in animal models, the timing of parturition relative to fetal maturation varies among viviparous species, indicative of phylogenetically different clocks and alarms; but what is clear is that important common pathways must converge to control the birth process. For example, in all species, parturition involves the transition of the myometrium from a relaxed to a highly excitable state, where the muscle rhythmically and forcefully contracts, softening the cervical extracellular matrix to allow distensibility and dilatation and thus a shearing of the fetal membranes to facilitate their rupture. We review a number of theories promulgated to explain how a variety of different timing mechanisms, including fetal membrane cell senescence, circadian endocrine clocks, and inflammatory and mechanical factors, are coordinated as initiators and effectors of parturition. Many of these factors have been independently described with a focus on specific tissue compartments.In this review, we put forth the core hypothesis that fetal membrane (amnion and chorion) senescence is the initiator of a coordinated, redundant signal cascade leading to parturition. Whether modified by oxidative stress or other factors, this process constitutes a counting device, i.e. a clock, that measures maturation of the fetal organ systems and the production of hormones and other soluble mediators (including alarmins) and that promotes inflammation and orchestrates an immune cascade to propagate signals across different uterine compartments. This mechanism in turn sensitizes decidual responsiveness and eventually promotes functional progesterone withdrawal in the myometrium, leading to increased myometrial cell contraction and the triggering of parturition. Linkage of these processes allows convergence and integration of the gestational clocks and alarms, prompting a timely and safe birth. In summary, we provide a comprehensive synthesis of the mediators that contribute to the timing of human labor. Integrating these concepts will provide a better understanding of human parturition and ultimately improve pregnancy outcomes. PMID- 27363418 TI - Identifying disrupted pathways by tracking altered modules in type 2 DM-related heart failure. AB - BACKGROUND: This study aimed to screen disrupted pathways in type 2 diabetes mellitus (T2DM) heart failure by systematically tracking the altered modules of reweighted protein-protein interaction (PPI) networks. METHODS: We implemented systematic identification and comparison of modules across non-T2DM and T2DM heart failure subjects by integrating gene expression data and PPI networks. The PPI networks of non-T2DM heart failure and T2DM heart failure were constructed and reweighted by means of Spearman's correlation coefficient (SCC). Subsequently, a clique-merging algorithm was used to explore the modules in the PPI network, followed by the identification of disrupted modules based on a maximum-weight bipartite matching and sorting in descending order. Finally, pathway enrichment analyses were conducted for genes in disrupted modules to determine the biological pathways in T2DM heart failure. RESULTS: By comparing the modules of non-T2DM heart failure and T2DM heart failure, 804 disrupted modules were explored. The genes in disrupted modules were significantly enriched in 39 categories (p < 1.00E-06). Of these, the most significant pathways were the focal adhesion, vascular endothelial growth factor (VEGF) signaling, and mitogen activated protein kinase (MAPK) signaling pathways. CONCLUSION: The identified disrupted pathways - focal adhesion, VEGF signaling, and MAPK signaling - might play important roles in the progression of T2DM heart failure. PMID- 27363419 TI - Parental and offspring factors in offspring's weight-loss efforts. AB - PURPOSE: Although weight-loss efforts in non-overweight adolescents and young adults are quite common, the relation between parental and offspring factors related to this behavior remains unclear. This study assessed the parental and offspring factors related to offspring's weight-loss efforts according to offspring's weight status. METHODS: Data pertaining to weight-loss efforts and weight status for 1026 families, including 1449 offspring (703 male and 749 female offspring, aged 10-25 years) and 1026 pairs of parents, were derived from the Korea National Health and Nutrition Examination Survey from 2010 to 2013. A generalized estimating equation was used to examine factors associated with offspring's weight-loss efforts after adjusting for intra-familial correlations. RESULTS: Weight-loss efforts in adolescents and young adults increased with offspring factors, such as female sex [OR (95 % CI), 2.64 (2.02-3.46)], overweight status [9.54 (6.66-13.67)], weight overestimation [2.96 (2.08-4.20)], and maternal weight-loss efforts [1.37 (1.05-1.79)], while weight-loss efforts decreased with offspring's weight underestimation [0.27 (0.19-0.37)], after adjusting for similar parental factors and intra-familial correlations. In non overweight adolescents and young adults, weight-loss efforts were associated with maternal weight-loss efforts [1.52 (1.11-2.08)] and offspring sex [female vs. male; 2.93 (2.14-4.01)], as well as offspring's weight underestimation [vs. accurate estimation; 0.15 (0.08-0.28)] or overestimation [vs. accurate estimation; 3.05 (2.13-4.38)]. In overweight adolescents and young adults, weight loss efforts were associated with offspring's weight underestimation [0.45 (0.28 0.71)]. CONCLUSIONS: Weight-loss efforts in adolescents and young adult offspring are associated with maternal weight-loss efforts, offspring's weight perception, and sex in non-overweight offspring, and offspring's weight perception in overweight offspring. PMID- 27363420 TI - Remembering Joan (Jan) Mary Anderson (1932-2015). AB - Joan Mary Anderson, known to most people as Jan, was born on May 12, 1932 in Dunedin, New Zealand. She died on August 28, 2015 in Canberra, Australia. To celebrate her life, we present here a brief biography, some comments on her discoveries in photosynthesis during a career spanning more than half a century, and reminiscences from family and friends. We remember this wonderful person who had an unflagging curiosity, creative ability to think laterally, enthusiasm, passion, generosity and love of color and culture. PMID- 27363421 TI - Effective Mental Health Screening in Adolescents: Should We Collect Data from Youth, Parents or Both? AB - Youth- and parent-rated screening measures derived from the Strengths and Difficulties Questionnaire (SDQ) and Development and Well-Being Assessment (DAWBA) were compared on their psychometric properties as predictors of caseness in adolescence (mean age 14). Successful screening was judged firstly against the likelihood of having an ICD-10 psychiatric diagnosis and secondly by the ability to discriminate between community (N = 252) and clinical (N = 86) samples (sample status). Both, SDQ and DAWBA measures adequately predicted the presence of an ICD 10 disorder as well as sample status. The hypothesis that there was an informant gradient was confirmed: youth self-reports were less discriminating than parent reports, whereas combined parent and youth reports were more discriminating-a finding replicated across a diversity of measures. When practical constraints only permit screening for caseness using either a parent or an adolescent informant, parents are the better source of information. PMID- 27363422 TI - Relationship of renal insufficiency and clinical features or comorbidities with clinical outcome in patients hospitalised for acute heart failure syndromes. AB - BACKGROUND: Renal insufficiency is a well-known predictor of adverse events in patients with acute heart failure syndromes (AHFS). However, it remains unclear whether there are subgroups of AHFS patients in whom renal insufficiency is related to a higher risk of adverse events because of the heterogeneity of this patient population. Therefore, we investigated the relationship between renal insufficiency, clinical features or comorbidities, and the risk of adverse events in patients with AHFS. METHODS AND RESULTS: Of 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 4628 patients (95.6%) were evaluated in the present study in order to assess the relationship of renal insufficiency and clinical features or comorbidities with all-cause mortality after admission. Renal insufficiency was defined as an estimated creatinine clearance of ?40 mL/min (calculated by the Cockcroft-Gault formula) at admission. The median follow-up period after admission was 524 (391-789) days. The all-cause mortality rate after admission was significantly higher in patients with renal insufficiency (36.7%) than in patients without renal insufficiency (14.4%). Stratified analysis was performed in order to explore the heterogeneity of the influence of renal insufficiency on all-cause mortality. This analysis revealed that an ischaemic aetiology and a history of diabetes, atrial fibrillation, serum sodium, and anaemia at admission had significant influences on the relationship between renal insufficiency and all-cause mortality. CONCLUSIONS: The present study demonstrated that the relationship between renal insufficiency and all-cause mortality of AHFS patients varies markedly with clinical features or comorbidities and the mode of presentation due to the heterogeneity of this patient population. PMID- 27363423 TI - Does the working temperature affect the outcome following microwave endometrial ablation? AB - BACKGROUND: Menorrhagia is a common gynaecological complaint, with significant burden to both its sufferers and health service providers. The first line of treatment is usually medical/pharmaceutical although in some cases surgery is required. There are now a number of minimally invasive surgical techniques available that ablate the uterine lining and prevent the need for the removal of the uterus. Microwave endometrial ablation (MEA) is one of these techniques, and this paper investigates the effect of the working temperature on outcome. METHODS: A retrospective case note review of women who underwent MEA between June 2000 and August 2004. All women had a hysteroscopy followed by MEA. The duration of the procedure and mean working temperature of the MEA treatment was calculated. Women were followed up 6-8 months after surgery. FINDINGS: Two hundred and eleven women underwent the procedure, with an average duration of menorrhagia of 30 months prior to the procedure. Eighty-nine percent attended follow-up, 80 % were satisfied with the procedure and 40 % were amenorrhoeic. When the procedure was performed at higher working temperature within the manufacturers guidelines women were more likely to be amenorrhoeic (78.4 vs. 77.1 degrees C, p = 0.014). CONCLUSION: MEA is more effective in treating menorrhagia when used at a higher operating temperature. PMID- 27363425 TI - Effects of Homologous Expression of 1,4-Benzoquinone Reductase and Homogentisate 1,2-Dioxygenase Genes on Wood Decay in Hyper-Lignin-Degrading Fungus Phanerochaete sordida YK-624. AB - We investigated the function of 1,4-benzoquinone reductase (BQR)- and homogentisate 1,2-dioxygenase (HGD)-like genes in wood degradation by Phanerochaete sordida YK-624, which exhibits high ligninolytic activity and selectivity. We determined homologous expression in the genomic and cDNA sequences of BQR- and HGD-like genes in P. sordida YK-624 (PsBQR and PsHGD). Both genes shared high homology (>=90 % amino acid sequence similarity) with the corresponding genes in Phanerochaete chrysosporium. These genes were co transformed with a reporter gene into an uracil auxotrophic mutant of P. sordida YK-624. The PsBQR and PsHGD co-transformants exhibited lower holocellulolytic activity and higher ligninolytic selectivity than the control transformants. In liquid culture with vanillin, both co-transformants significantly accelerated vanillin degradation. Thus, we suggest that the rapid metabolism of low-molecular weight lignin fragments, due to the homologous expression of BQR- and HGD-like genes, affects quinone redox cycling to produce hydroxyl radicals, thereby decreasing holocellulose degradation and increasing ligninolytic selectivity. PMID- 27363424 TI - Influence of a CYP1A2 polymorphism on post-exercise heart rate variability in response to caffeine intake: a double-blind, placebo-controlled trial. AB - BACKGROUND: Proposed differences in caffeine metabolism due to the CYP1A2*1F polymorphism have been linked to variations in cardiovascular disease risk. AIMS: We examined the influence of a CYP1A2*1F polymorphism on post-exercise heart rate variability (HRV) in response to caffeine intake. METHODS: Volunteers were identified as A/A homozygotes (A/A; 4 females and 7 males; age: 25.3 +/- 4.1 years; BMI: 25.9 +/- 4.4 kg/m2) or C allele carriers (C allele; 3 females and 6 males; age: 25.5 +/- 2.8 years; BMI: 26.6 +/- 5.0 kg/m2) for participation in a repeated measures, counterbalanced, double-blind, placebo-controlled trial. Participants chewed three pieces of gum containing either caffeine (CAF) (100 mg/piece) or placebo for 5 min. Thereafter, participants cycled for 15 min at 75 % of their peak oxygen consumption. Eight HRV indices computed during 5 min at baseline (BASE), 0-5 min after exercise (POST1), and 5-10 min after exercise (POST2) were used for analysis. RESULTS: No significant group differences were detected in HRV indices at BASE, POST1, or POST2 during both trials (p > 0.05). Rate of recovery (POST2-POST1) for the square root of the mean of squared differences between successive RR intervals (RMSSD) was significantly different between A/A (6.0 +/- 2.5 ms) and C allele (3.6 +/- 2.5 ms) groups during the CAF trial (p = 0.048). CONCLUSIONS: Rate of RMSSD recovery was the only variable influenced by the CYP1A2*IF polymorphism during post-exercise in response to caffeine intake. Thus, the CYP1A2*1F polymorphism did not overtly influence the effects of caffeine intake on post-exercise HRV. PMID- 27363427 TI - A brushfire in the eye. PMID- 27363426 TI - Heme acquisition in the parasitic filarial nematode Brugia malayi. AB - Nematodes lack a heme biosynthetic pathway and must acquire heme from exogenous sources. Given the indispensable role of heme, this auxotrophy may be exploited to develop drugs that interfere with heme uptake in parasites. Although multiple heme-responsive genes (HRGs) have been characterized within the free-living nematode Caenorhabditis elegans, we have undertaken the first study of heme transport in Brugia malayi, a causative agent of lymphatic filariasis. Through functional assays in yeast, as well as heme analog, RNAi, and transcriptomic experiments, we have shown that the heme transporter B. malayi HRG-1 (BmHRG-1) is indeed functional in B. malayi In addition, BmHRG-1 localizes both to the endocytic compartments and cell membrane when expressed in yeast cells. Transcriptomic sequencing revealed that BmHRG-1, BmHRG-2, and BmMRP-5 (all orthologs of HRGs in C. elegans) are down-regulated in heme-treated B. malayi, as compared to non-heme-treated control worms. Likely because of short gene lengths, multiple exons, other HRGs in B. malayi (BmHRG-3-6) remain unidentified. Although the precise mechanisms of heme homeostasis in a nematode with the ability to acquire heme remains unknown, this study clearly demonstrates that the filarial nematode B. malayi is capable of transporting exogenous heme.-Luck, A. N., Yuan, X., Voronin, D., Slatko, B. E., Hamza, I., Foster, J. M. Heme acquisition in the parasitic filarial nematode Brugia malayi. PMID- 27363428 TI - Thiols of flagellar proteins are essential for progressive motility in human spermatozoa. AB - Male infertility is a disorder of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse. The presence of low-motile or immotile spermatozoa is one of many causes of infertility; however, this observation provides little or no information regarding the pathogenesis of the malfunction. Good sperm motility depends on correct assembly of the sperm tail in the testis and efficient maturation during epididymal transit. Thiols of flagellar proteins, such as outer dense fibre protein 1 (ODF1), are oxidised to form disulfides during epididymal transit and the spermatozoa become motile. This study was designed to determine how oxidative changes in protein thiol status affect progressive motility in human spermatozoa. Monobromobimane (mBBr) was used as a specific thiol marker and disruptor of sperm progressive motility. When mBBr was blocked by dithiothreitol it did not promote motility changes. The analysis of mBBr-treated spermatozoa revealed a reduction of progressive motility and an increased number of spermatozoa with non-progressive motility without affecting ATP production. Laser confocal microscopy and western blot analysis showed that one of the mBBr positive proteins reacted with an antibody to ODF1. Monobromobimane fluorescence intensity of the sperm tail was lower in normozoospermic than asthenozoospermic men, suggesting that thiol oxidation in spermatozoa of asthenozoospermic men is incomplete. Our findings indicate that mBBr affects the thiol status of ODF1 in human spermatozoa and interferes with progressive motility. PMID- 27363430 TI - MPs condemn lack of rigour in how UK's L6bn science budget is spent. PMID- 27363429 TI - Collaborative targeted maximum likelihood estimation for variable importance measure: Illustration for functional outcome prediction in mild traumatic brain injuries. AB - Standard statistical practice used for determining the relative importance of competing causes of disease typically relies on ad hoc methods, often byproducts of machine learning procedures (stepwise regression, random forest, etc.). Causal inference framework and data-adaptive methods may help to tailor parameters to match the clinical question and free one from arbitrary modeling assumptions. Our focus is on implementations of such semiparametric methods for a variable importance measure (VIM). We propose a fully automated procedure for VIM based on collaborative targeted maximum likelihood estimation (cTMLE), a method that optimizes the estimate of an association in the presence of potentially numerous competing causes. We applied the approach to data collected from traumatic brain injury patients, specifically a prospective, observational study including three US Level-1 trauma centers. The primary outcome was a disability score (Glasgow Outcome Scale - Extended (GOSE)) collected three months post-injury. We identified clinically important predictors among a set of risk factors using a variable importance analysis based on targeted maximum likelihood estimators (TMLE) and on cTMLE. Via a parametric bootstrap, we demonstrate that the latter procedure has the potential for robust automated estimation of variable importance measures based upon machine-learning algorithms. The cTMLE estimator was associated with substantially less positivity bias as compared to TMLE and larger coverage of the 95% CI. This study confirms the power of an automated cTMLE procedure that can target model selection via machine learning to estimate VIMs in complicated, high-dimensional data. PMID- 27363432 TI - Voluntary Second Opinions in Pediatric Bone and Soft Tissue Pathology: A Retrospective Review of 1601 Cases From a Single Mesenchymal Tumor Consultation Service. AB - The diagnosis of bone and soft tissue tumors in children is challenging. These lesions are especially difficult for general pathologists. We reviewed our experience with pediatric mesenchymal tumors sent in consultation to our service, with the goal of identifying issues that most often prompted second-opinion referral. Roughly 16 000 cases were seen in toto, of which 1601 occurred in children. These included 491 bone cases and 1110 soft tissue cases. The cases were referred by private practices/nonacademic medical centers (85%), academic medical centers (8%), and pediatric hospitals (7%). Reasons for referral were (a) self-perceived lack of experience with pediatric mesenchymal tumors (n = 930), (b) second opinion requested by the clinician or patient (n = 132), and (c) perceived or real need for ancillary studies not available at the referring institution (n = 116). The referring pathologists suggested a diagnosis for 670 cases; of these, 476 (71%) were in essential agreement with our final diagnosis. Of the remaining, 139 (21%) were considered "minor disagreements" and 55 (8%) "major disagreements." The "major disagreement" cases could be divided into (a) malignant tumors submitted with benign diagnoses (58%), (b) benign tumors submitted with malignant diagnoses (25%), (c) nonneoplastic conditions submitted as representing neoplasms (11%), and (d) neoplasm submitted as representing nonneoplastic conditions (6%). Pediatric mesenchymal tumors comprised 10% of cases sent to our mesenchymal tumor consultation practice. The rates of diagnostic disagreement found in this study are roughly in accordance with prior studies of mandatory and voluntary second opinion in adult soft tissue tumors. Given the rarity of these tumors, expert second opinion may be of value. PMID- 27363431 TI - The effect of HIV-1 Vif polymorphisms on A3G anti-viral activity in an in vivo mouse model. AB - Humans encode seven APOBEC3 proteins (A-H), with A3G, 3F and 3H as the major factors restricting HIV-1 replication. HIV-1, however, encodes Vif, which counteracts A3 proteins by chaperoning them to the proteasome where they are degraded. Vif polymorphisms found in HIV-1s isolated from infected patients have varying anti-A3G potency when assayed in vitro, but there are few studies demonstrating this in in vivo models. Here, we created Friend murine leukemia viruses encoding vif alleles that were previously shown to differentially neutralize A3G in cell culture or that were originally found in primary HIV-1 isolates. Infection of transgenic mice expressing different levels of human A3G showed that these naturally occurring Vif variants differed in their ability to counteract A3G during in vivo infection, although the effects on viral replication were not identical to those seen in cultured cells. We also found that the polymorphic Vifs that attenuated viral replication reverted to wild type only in A3G transgenic mice. Finally, we found that the level of A3G-mediated deamination was inversely correlated with the level of viral replication. This animal model should be useful for studying the functional significance of naturally occurring vif polymorphisms, as well as viral evolution in the presence of A3G. PMID- 27363433 TI - Triple Hit Lymphoma: Rare Cases With Less Dire Than Usual Prognosis. AB - Triple hit lymphomas are a subset of so-called double hit non-Hodgkin lymphomas exhibiting simultaneous gene translocations/disruption of MYC, BCL2, and BCL6; however, their overlapping morphologic features and complex genetic rearrangements can render classification and prognostication vexing. Clinically triple hit lymphomas are thought to demonstrate aggressive behavior, similar to or worse than that of double hit lymphomas. Only rare reports of long term survivors exist and raise the possibility that unidentified morphologic, immunologic, or cytogenetic differences may impart a less adverse prognosis than current literature and opinion may suggest. Here we report 3 such cases with less aggressive behavior. Cases such as these may prove useful in comparing outcomes, and underlying mechanisms of tumor progression, in aggressive non-Hodgkin lymphomas. PMID- 27363434 TI - Being Human: A Qualitative Interview Study Exploring Why a Telehealth Intervention for Management of Chronic Conditions Had a Modest Effect. AB - BACKGROUND: Evidence of benefit for telehealth for chronic conditions is mixed. Two linked randomized controlled trials tested the Healthlines Service for 2 chronic conditions: depression and high risk of cardiovascular disease (CVD). This new telehealth service consisted of regular telephone calls from nonclinical, trained health advisers who followed standardized scripts generated by interactive software. Advisors facilitated self-management by supporting participants to use Web-based resources and helped to optimize medication, improve treatment adherence, and encourage healthier lifestyles. Participants were recruited from primary care. The trials identified moderate (for depression) or partial (for CVD risk) effectiveness of the Healthlines Service. OBJECTIVE: An embedded qualitative study was undertaken to help explain the results of the 2 trials by exploring mechanisms of action, context, and implementation of the intervention. METHODS: Qualitative interview study of 21 staff providing usual health care or involved in the intervention and 24 patients receiving the intervention. RESULTS: Interviewees described improved outcomes in some patients, which they attributed to the intervention, describing how components of the model on which the intervention was based helped to achieve benefits. Implementation of the intervention occurred largely as planned. However, contextual issues in patients' lives and some problems with implementation may have reduced the size of effect of the intervention. For depression, patients' lives and preferences affected engagement with the intervention: these largely working-age patients had busy and complex lives, which affected their ability to engage, and some patients preferred a therapist-based approach to the cognitive behavioral therapy on offer. For CVD risk, patients' motivations adversely affected the intervention whereby some patients joined the trial for general health improvement or from altruism, rather than motivation to make lifestyle changes to address their specific risk factors. Implementation was not optimal in the early part of the CVD risk trial owing to technical difficulties and the need to adapt the intervention for use in practice. For both conditions, enthusiastic and motivated staff offering continuity of intervention delivery tailored to individual patients' needs were identified as important for patient engagement with telehealth; this was not delivered consistently, particularly in the early stages of the trials. Finally, there was a lack of active engagement from primary care. CONCLUSIONS: The conceptual model was supported and could be used to develop further telehealth interventions for chronic conditions. It may be possible to increase the effectiveness of this, and similar interventions, by attending to the human as well as the technical aspects of telehealth: offering it to patients actively wanting the intervention, ensuring continuity of delivery by enthusiastic and motivated staff, and encouraging active engagement from primary care staff. PMID- 27363435 TI - Erratum to: Single-cell whole genome sequencing reveals no evidence for common aneuploidy in normal and Alzheimer's disease neurons. PMID- 27363436 TI - About This Continuing Medical Education Activity. PMID- 27363437 TI - Pharmacologic Considerations in the Treatment of Hepatitis C Virus in Persons With HIV. AB - Roughly one-third of individuals living with the human immunodeficiency virus (HIV) are coinfected with the hepatitis C virus (HCV) due to shared routes of transmission. HIV accelerates the progression of HCV disease; thus, coinfected individuals are at high priority for HCV treatment. Several new HCV therapies, called direct-acting antiviral agents (DAAs), are available that achieve cure rates of >90% in many patient populations including individuals with HIV. The primary consideration in treating HCV in HIV-infected persons is the potential for drug interactions. We describe the clinical pharmacology and drug interaction potential of the DAAs, review the interaction data with DAAs and antiretroviral agents, and identify the knowledge gaps in the pharmacologic aspects of treating HCV in individuals with HIV coinfection. This review will focus on DAAs that have received regulatory approval in the United States and Europe and agents in late stages of clinical development. PMID- 27363438 TI - Management of Hepatitis C/HIV Coinfection in the Era of Highly Effective Hepatitis C Virus Direct-Acting Antiviral Therapy. AB - The increased life expectancy of persons infected with human immunodeficiency virus (HIV) treated with antiretroviral therapy (ART) has resulted in renewed attention to non-HIV-related diseases exacerbated by HIV infection. Coinfection with hepatitis C virus (HCV) is a particular area of concern, as the global prevalence has been estimated at 2.5-5 million people. In this article, we discuss the epidemiology of HCV infection and reinfection, HCV-related liver disease progression in the era of effective ART, and the efficacy of emerging HCV treatment strategies in persons with HIV/HCV coinfection. New data regarding treatment of persons with HIV/HCV coinfection suggest that HCV treatment should be a priority in those with HIV. Results from recent studies using all-oral HCV regimens have shown high rates of sustained virologic response in both clinical trials and real-world settings. A multidisciplinary approach to HCV treatment in those with HIV is recommended for optimal patient management. Following HCV cure, practitioners also need to be mindful of the risks for HCV reinfection and educate patients on protective measures. PMID- 27363440 TI - Kinases as Novel Therapeutic Targets in Asthma and Chronic Obstructive Pulmonary Disease. AB - Multiple kinases play a critical role in orchestrating the chronic inflammation and structural changes in the respiratory tract of patients with asthma and chronic obstructive pulmonary disease (COPD). Kinases activate signaling pathways that lead to contraction of airway smooth muscle and release of inflammatory mediators (such as cytokines, chemokines, growth factors) as well as cell migration, activation, and proliferation. For this reason there has been great interest in the development of kinase inhibitors as anti-inflammatory therapies, particular where corticosteroids are less effective, as in severe asthma and COPD. However, it has proven difficult to develop selective kinase inhibitors that are both effective and safe after oral administration and this has led to a search for inhaled kinase inhibitors, which would reduce systemic exposure. Although many kinases have been implicated in inflammation and remodeling of airway disease, very few classes of drug have reached the stage of clinical studies in these diseases. The most promising drugs are p38 MAP kinases, isoenzyme-selective PI3-kinases, Janus-activated kinases, and Syk-kinases, and inhaled formulations of these drugs are now in development. There has also been interest in developing inhibitors that block more than one kinase, because these drugs may be more effective and with less risk of losing efficacy with time. No kinase inhibitors are yet on the market for the treatment of airway diseases, but as kinase inhibitors are improved from other therapeutic areas there is hope that these drugs may eventually prove useful in treating refractory asthma and COPD. PMID- 27363442 TI - Manipulating Angiogenesis by Targeting Endothelial Metabolism: Hitting the Engine Rather than the Drivers-A New Perspective? AB - Excessive angiogenesis (i.e., the formation of new blood vessels) contributes to different pathologies, among them cancer and ocular disorders. Conversely, dysfunction of endothelial cells (ECs) contributes to cardiovascular complications, as is the case in diabetes. Inhibition of pathologic angiogenesis in blinding eye disease and cancer by targeting growth factors such as vascular endothelial growth factor has become an accepted therapeutic strategy. However, recent studies also unveiled the emerging importance of EC metabolism in controlling angiogenesis. In this overview, we will discuss recent insights in the metabolic regulation of angiogenesis, focusing on the best-characterized metabolic pathways, and highlight deregulation of EC metabolism in cancer and diabetes. We will give an outlook on how targeting EC metabolism can be used for blocking pathologic angiogenesis and for normalizing EC dysfunction. PMID- 27363443 TI - PhytoCRISP-Ex: a web-based and stand-alone application to find specific target sequences for CRISPR/CAS editing. AB - BACKGROUND: With the emerging interest in phytoplankton research, the need to establish genetic tools for the functional characterization of genes is indispensable. The CRISPR/Cas9 system is now well recognized as an efficient and accurate reverse genetic tool for genome editing. Several computational tools have been published allowing researchers to find candidate target sequences for the engineering of the CRISPR vectors, while searching possible off-targets for the predicted candidates. These tools provide built-in genome databases of common model organisms that are used for CRISPR target prediction. Although their predictions are highly sensitive, the applicability to non-model genomes, most notably protists, makes their design inadequate. This motivated us to design a new CRISPR target finding tool, PhytoCRISP-Ex. Our software offers CRIPSR target predictions using an extended list of phytoplankton genomes and also delivers a user-friendly standalone application that can be used for any genome. RESULTS: The software attempts to integrate, for the first time, most available phytoplankton genomes information and provide a web-based platform for Cas9 target prediction within them with high sensitivity. By offering a standalone version, PhytoCRISP-Ex maintains an independence to be used with any organism and widens its applicability in high throughput pipelines. PhytoCRISP-Ex out pars all the existing tools by computing the availability of restriction sites over the most probable Cas9 cleavage sites, which can be ideal for mutant screens. CONCLUSIONS: PhytoCRISP-Ex is a simple, fast and accurate web interface with 13 pre-indexed and presently updating phytoplankton genomes. The software was also designed as a UNIX-based standalone application that allows the user to search for target sequences in the genomes of a variety of other species. PMID- 27363444 TI - In Vitro PET Imaging of a Miniature Ventricular Assist Device. AB - Interactions between the life-sustaining ventricular assist devices and diagnostic therapies must be carefully considered to decrease the risk of inaccurate diagnostic imaging or pump failure. METHODS: The MVAD((r)) pump, currently under investigational use, was tested for interaction with radiotracers in an in vitro flow-loop study. The radiotracers (18)F-sodium fluoride and (18)F FDG were injected into a closed loop to determine the feasibility of direct imaging of the MVAD((r)) pump in a PET scanner. RESULTS: No real-time changes were observed in pump operation, and there were no statistical differences in pump parameters (power consumption, speed, and estimated flow rate) between the baseline and circulation conditions. In addition, no effect was observed on any external components, including the permissive-action-link controller and the batteries powering the device. Imaging of the internal pump components was possible, with obscuration observed only in the portion of the pump where the spinning impeller is located. Retention of radiotracer in the pump components after circulation was minimal (<1%). CONCLUSION: PET imaging is an attractive diagnostic tool for patients with a ventricular assist device and may have additional utility outside its current use, detection of infection. PMID- 27363445 TI - Functioning Metastases from Thyroid Papillary Carcinoma in Bone. AB - Functioning thyroid metastases are a rare cause of hyperthyroidism. Most are follicular carcinoma. Here, we report a case in which a 62-y-old man with a history of right subtotal thyroidectomy for a benign adenoma complained of symptoms of hyperthyroidism associated with left arm pain. Biopsy of a humeral lesion was consistent with papillary carcinoma metastatic from the thyroid. Postoperatively, the patient received a cumulative dose of 14.8 GBq of 131I with good control of the hyperthyroidism but without eradication of the bone metastasis. PMID- 27363446 TI - Detection of Intrathoracic Bleeding by 99mTc-Labeled Red Blood Cell SPECT/CT After Wedge Biopsy of Pulmonary Angiosarcoma. AB - A 52-y-old man presenting with dyspnea and a massive effusion in the right pleural cavity underwent wedge biopsies of pulmonary lesions found on thoracic CT, leading to a diagnosis of pleural angiosarcoma. Bleeding developed postoperatively and was investigated using pulmonary CT angiography, which failed to identify a site of active bleeding. (99m)Tc-labeled red blood cell (RBC) SPECT/CT of the chest was performed, and the site was rapidly located. To our knowledge, this is the first case reported in the literature of localization of intrathoracic bleeding using (99m)Tc-RBC SPECT/CT. PMID- 27363447 TI - 18F-FDG PET/CT Imaging of Hodgkin Lymphoma in a Child with Common Variable Immunodeficiency. AB - Common variable immunodeficiency is characterized by low levels of serum immunoglobulins and antibodies, recurrent infections, and a predisposition to malignancy. Here, we present the 18F-FDG PET/CT findings of a 7-y-old boy with common variable immunodeficiency and Hodgkin lymphoma. PMID- 27363448 TI - Mediastinal Masses in Nuclear Medicine Studies: A Diagnostic Algorithm. AB - There are multiple reasons for an anterior mediastinal mass. In this case, we discuss possible etiologies and offer an algorithm to narrow the differential diagnosis. When the mass cannot be diagnosed radiographically, the next step in imaging is a physiologic assessment with radionuclide modalities. PMID- 27363449 TI - The First Attempt at Non-Linear in Silico Prediction of Sampling Rates for Polar Organic Chemical Integrative Samplers (POCIS). AB - Modeling and prediction of polar organic chemical integrative sampler (POCIS) sampling rates (Rs) for 73 compounds using artificial neural networks (ANNs) is presented for the first time. Two models were constructed: the first was developed ab initio using a genetic algorithm (GSD-model) to shortlist 24 descriptors covering constitutional, topological, geometrical and physicochemical properties and the second model was adapted for Rs prediction from a previous chromatographic retention model (RTD-model). Mechanistic evaluation of descriptors showed that models did not require comprehensive a priori information to predict Rs. Average predicted errors for the verification and blind test sets were 0.03 +/- 0.02 L d(-1) (RTD-model) and 0.03 +/- 0.03 L d(-1) (GSD-model) relative to experimentally determined Rs. Prediction variability in replicated models was the same or less than for measured Rs. Networks were externally validated using a measured Rs data set of six benzodiazepines. The RTD-model performed best in comparison to the GSD-model for these compounds (average absolute errors of 0.0145 +/- 0.008 L d(-1) and 0.0437 +/- 0.02 L d(-1), respectively). Improvements to generalizability of modeling approaches will be reliant on the need for standardized guidelines for Rs measurement. The use of in silico tools for Rs determination represents a more economical approach than laboratory calibrations. PMID- 27363460 TI - Differential Effects of Reward Drive and Rash Impulsivity on the Consumption of a Range of Hedonic Stimuli. AB - Background and aims Impulsivity has consistently been associated with over consumption and addiction. Recent research has reconceptualized impulsivity as a two-dimensional construct ( Dawe, Gullo, & Loxton, 2004 ). This study explores the relationship of the two components of impulsivity, reward drive (RD) and rash impulsivity (RI), on a broad group of 23 hedonic consumption behaviors (e.g., gambling, substance use, eating, and media use). We tentatively grouped the behaviors into three descriptive classes: entertainment, foodstuffs, and illicit activities and substances. Results RD and RI positively predicted elevated levels of consumption in a community sample (N=5,391; 51% female), for the vast majority of the behaviors considered. However, the effect sizes for RD and RI varied significantly depending on the behavior; a pattern that appeared to be at least partially attributable to the class of consumption. Results support the view that RD is related more strongly to the consumption of products that provide social engagement or a sense of increased status; whereas RI better reflects an approach toward illicit or restricted products that are intensely rewarding with clear negative consequences. Discussion and conclusion Results support the utility of the two-factor model of impulsivity in explaining individual differences in patterns of hedonic consumption in the general population. We discuss findings in terms of strengthening current conceptualizations of RI and RD as having distinct implications with respect to health-related behaviors. PMID- 27363461 TI - Anxiety, Gambling Activity, and Neurocognition: A Dimensional Approach to a Non Treatment-Seeking Sample. AB - Background and aims Previous analyses have highlighted significant associations between gambling disorder (GD)/subsyndromal GD and increased rates of anxiety symptoms and anxiety disorders relative to the general population. However, less is known about how anxiety symptoms influence the clinical presentation of gambling problems. The objective of this study was to evaluate the association between anxiety symptoms, gambling activity, and neurocognition across the spectrum of gambling behavior. Methods The sample consisted of 143 non-treatment seeking young adults (aged 18-29 years), in which 63 individuals (44.1%) were classified as recreational gamblers, 47 (32.9%) as having subsyndromal GD, and 33 (23.1%) met criteria for GD. Results The main findings were: (a) there was a positive correlation between anxiety severity and gambling severity measured by the number of DSM-5 GD criteria met; (b) there was a positive correlation between anxiety severity and attentional impulsiveness; (c) subjects with suicidality presented higher levels of anxiety; and (d) the severity of anxiety symptoms was negatively correlated with the quality of life. Discussion and conclusions This study suggests that anxiety may be associated with relevant clinical variables in the broad spectrum of gambling activity. Therefore, proper management of anxiety symptoms might improve the clinical presentation of gamblers in different areas. PMID- 27363462 TI - Gambling with Rose-Tinted Glasses on: Use of Emotion-Regulation Strategies Correlates with Dysfunctional Cognitions in Gambling Disorder Patients. AB - Background and aims Existing research shows that gambling disorder patients (GDPs) process gambling outcomes abnormally when compared against healthy controls (HCs). These anomalies present the form of exaggerated or distorted beliefs regarding the expected utility of outcomes and one's ability to predict or control gains and losses, as well as retrospective reinterpretations of what caused them. This study explores the possibility that the emotional regulation strategies GDPs use to cope with aversive events are linked to these cognitions. Methods 41 GDPs and 45 HCs, matched in sociodemographic variables, were assessed in gambling severity, emotion-regulation strategies (cognitive emotion-regulation questionnaire, CERQ), and gambling-related cognitions (gambling-related cognitions scale, GRCS). Results GDPs showed higher scores in all gambling related cognition dimensions. Regarding emotion regulation, GDPs were observed to use self-blame and catastrophizing, but also positive refocusing, more often than controls. Additionally, in GDPs, putatively adaptive CERQ strategies shared a significant portion of variance with South Oaks gambling screen severity and GRCS beliefs. Shared variability was mostly attributable to the roles of refocusing on planning and putting into perspective at positively predicting severity and the interpretative bias (GDPs propensity to reframe losses in a more benign way), respectively. Discussion and conclusions Results show links between emotion regulation strategies and problematic gambling-related behaviors and cognitions. The pattern of those links supports the idea that GDPs use emotion-regulation strategies, customarily regarded as adaptive, to cope with negative emotions, so that the motivational and cognitive processing of gambling outcomes becomes less effective in shaping gambling-related behavior. PMID- 27363463 TI - Experiential Avoidance and Technological Addictions in Adolescents. AB - Background and aims This study focuses on the use of popular information and communication technologies (ICTs) by adolescents: the Internet, mobile phones, and video games. The relationship of ICT use and experiential avoidance (EA), a construct that has emerged as underlying and transdiagnostic to a wide variety of psychological problems, including behavioral addictions, is examined. EA refers to a self-regulatory strategy involving efforts to control or escape from negative stimuli such as thoughts, feelings, or sensations that generate strong distress. This strategy, which may be adaptive in the short term, is problematic if it becomes an inflexible pattern. Thus, the aim of this study was to explore whether EA patterns were associated with addictive or problematic use of ICT in adolescents. Methods A total of 317 students of the Spanish southeast between 12 and 18 years old were recruited to complete a questionnaire that included questions about general use of each ICTs, an experiential avoidance questionnaire, a brief inventory of the Big Five personality traits, and specific questionnaires on problematic use of the Internet, mobile phones, and video games. Results Correlation analysis and linear regression showed that EA largely explained results regarding the addictive use of the Internet, mobile phones, and video games, but not in the same way. As regards gender, boys showed a more problematic use of video games than girls. Concerning personality factors, conscientiousness was related to all addictive behaviors. Discussion and conclusions We conclude that EA is an important construct that should be considered in future models that attempt to explain addictive behaviors. PMID- 27363464 TI - Internet Gaming Disorder Among Slovenian Primary Schoolchildren: Findings From a Nationally Representative Sample of Adolescents. AB - Background and aims Since the inclusion of Internet Gaming Disorder (IGD) in the latest (fifth) edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a tentative disorder, a few psychometric screening instruments have been developed to assess IGD, including the 9-item Internet Gaming Disorder Scale - Short-Form (IGDS9-SF) - a short, valid, and reliable instrument. Methods Due to the lack of research on IGD in Slovenia, this study aimed to examine the psychometric properties of the IGDS9-SF in addition to investigating the prevalence rates of IGD in a nationally representative sample of eighth graders from Slovenia (N = 1,071). Results The IGDS9-SF underwent rigorous psychometric scrutiny in terms of validity and reliability. Construct validation was investigated with confirmatory factor analysis to examine the factorial structure of the IGDS9-SF and a unidimensional structure appeared to fit the data well. Concurrent and criterion validation were also investigated by examining the association between IGD and relevant psychosocial and game-related measures, which warranted these forms of validity. In terms of reliability, the Slovenian version IGDS9-SF obtained excellent results regarding its internal consistency at different levels, and the test appears to be a valid and reliable instrument to assess IGD among Slovenian youth. Finally, the prevalence rates of IGD were found to be around 2.5% in the whole sample and 3.1% among gamers. Discussion and conclusion Taken together, these results illustrate the suitability of the IGDS9-SF and warrants further research on IGD in Slovenia. PMID- 27363465 TI - Adaptation and Psychometric Evaluation of the Young Diagnostic Questionnaire (YDQ) for Parental Assessment of Adolescent Problematic Internet Use. AB - Background and aims The surge of problematic Internet use in adolescents is a continuously growing problem across the globe. To our knowledge, to date valid questionnaire-based measurement of problematic Internet use is possible only by self-assessment. The objective for the present study was to adapt an established instrument for a parental assessment of adolescent problematic Internet use and to evaluate the psychometric properties of this questionnaire. Methods Data were collected from a representative German sample of 1,000 parents of adolescents aged between 12 and 17 years using a standardized questionnaire. To assess problematic Internet use, we adapted the established Young Diagnostic Questionnaire by rewording the items to survey a parental rating instead of a self-report ("Parental version of the Young Diagnostic Questionnaire," PYDQ). Additionally, we assessed the Internet usage time, parental monitoring, family functioning, school performance of the adolescent, and parent-adolescent conflicts. We conducted a confirmatory factor analysis based on the 8 items of the PYDQ modeled as categorical indicators and one latent factor using a robust weighted least squares estimator. We also calculated a reliability coefficient, the acceptance of the instrument, and performed correlation analyses. Results The unidimensional model showed excellent global goodness-of-fit (chi(2)/df = 1.65, RMSEA = 0.03, CFI = 0.99, TLI = 0.99) and satisfactory factor loadings (standardized values ranged from 0.60 to 0.77). We observed a reliability coefficient of 0.70, a good acceptance of the instrument, and the correlation analyses indicated the construct validity of the PYDQ. Discussion and conclusion The proposed PYDQ is a suitable instrument for parental assessment of adolescent problematic Internet use. PMID- 27363466 TI - Exercise Addiction in Athletes and Leisure Exercisers: The Moderating Role of Passion. AB - Background and aims Recently, empirical research has linked obsessive passion to the etiology of exercise addiction, and the conceptual reason behind the fact that the latter is more prevalent in athletes than leisure exercisers has been challenged. The aim of this study was to determine the link between exercise addiction and harmonious passion, obsessive passion, and dedication to sports, in the context of athletic levels. Method A sample comprised of low- and high-level competitive athletes and non-competitive leisure exercisers (n = 313) was examined, in a cross-sectional design, in which participants completed the Spanish validated versions of the Exercise Addiction Inventory (Sicilia, Alias Garcia, Ferriz, & Moreno-Murcia, 2013) and Passion Scale (Chamarro et al., 2015). Results Obsessive passion and dedication to sports emerged as strong predictors of exercise addiction. Competitive athletes scored higher than leisure exercisers on all measures. Athletes competing at low and high levels only differed in dedication to their sports from each other. Team-sports athletes reported greater harmonious and obsessive passions, and dedication to sports, but not different exercise addictions, than people taking part in individual sports. Conclusions The concept of exercise addiction is not a plain and independent construct and may not reflect a psychological dysfunction in the athletic population. Athletes could interpret exercise addiction screening-items differently from non-athletes. Athletes in team sports report greater passion and dedication than those practicing individual sports. PMID- 27363467 TI - Controlling the Integration of Polyvinylpyrrolidone onto Substrate by Quartz Crystal Microbalance with Dissipation To Achieve Excellent Protein Resistance and Detoxification. AB - Blood purification systems, in which the adsorbent removes exogenous and endogenous toxins from the blood, are widely used in clinical practice. To improve the protein resistance of and detoxification by the adsorbent, researchers can modify the adsorbent with functional molecules, such as polyvinylpyrrolidone (PVP). However, achieving precise control of the functional molecular density, which is crucial to the activity of the adsorbent, remains a significant challenge. In the present study, we prepared a model system for blood purification adsorbents in which we controlled the integration density of PVP molecules of different molecular weights on an Au substrate by quartz crystal microbalance with dissipation (QCM-D). We characterized the samples with atomic force microscopy, X-ray photoelectron spectroscopy, and QCM-D and found that the molecular density and the chain length of the PVP molecules played important roles in determining the properties of the sample. At the optimal condition, the modified sample demonstrated strong resistance to plasma proteins, decreasing the adsorption of human serum albumin (HSA) and fibrinogen (Fg) by 92.5% and 79.2%, respectively. In addition, the modified sample exhibited excellent detoxification, and the adsorption of bilirubin increased 2.6-fold. Interestingly, subsequent atomistic molecular dynamics simulations indicated that the favorable interactions between PVP and bilirubin were dominated by hydrophobic interactions. An in vitro platelet adhesion assay showed that the adhesion of platelets on the sample decreased and that the platelets were maintained in an inactivated state. The CCK-8 assay indicated that the modified sample exhibited negligible cytotoxicity to L929 cells. These results demonstrated that our method holds great potential for the modification of adsorbents in blood purification systems. PMID- 27363469 TI - Molecular Characterization of the alpha-Galactosidase SCO0284 from Streptomyces coelicolor A3(2), a Family 27 Glycosyl Hydrolase. AB - The SCO0284 gene of Streptomyces coelicolor A3(2) is predicted to encode an alpha galactosidase (680 amino acids) belonging to glycoside hydrolase family 27. In this study, the SCO0284 coding region was cloned and overexpressed in Streptomyces lividans TK24. The mature form of SCO0284 (641 amino acids, 68 kDa) was purified from culture broth by gel filtration chromatography, with 83.3-fold purification and a yield of 11.2%. Purified SCO0284 showed strong activity against p-nitrophenyl-alpha-D-galactopyranoside, melibiose, raffinose, and stachyose, and no activity toward lactose, agar (galactan), and neoagarooligosaccharides, indicating that it is an alpha-galactosidase. Optimal enzyme activity was observed at 40 degrees C and pH 7.0. The addition of metal ions or EDTA did not affect the enzyme activity, indicating that no metal cofactor is required. The kinetic parameters Vmax and Km for p-nitrophenyl-alpha D-galactopyranoside were 1.6 mg/ml (0.0053 M) and 71.4 U/mg, respectively. Thin layer chromatography and mass spectrometry analysis of the hydrolyzed products of melibiose, raffinose, and stachyose showed perfect matches with the masses of the sodium adducts of the hydrolyzed products, galactose (M+Na, 203), melibiose (M+Na, 365), and raffinose (M+Na, 527), respectively, indicating that it specifically cleaves the alpha-1,6-glycosidic bond of the substrate, releasing the terminal D-galactose. PMID- 27363468 TI - Characterization of an L-arabinose isomerase from Bacillus coagulans NL01 and its application for D-tagatose production. AB - BACKGROUND: L-arabinose isomerase (AI) is a crucial catalyst for the biotransformation of D-galactose to D-tagatose. In previous reports, AIs from thermophilic bacterial strains had been wildly researched, but the browning reaction and by-products formed at high temperatures restricted their applications. By contrast, AIs from mesophilic Bacillus strains have some different features including lower optimal temperatures and lower requirements of metallic cofactors. These characters will be beneficial to the development of a more energy-efficient and safer production process. However, the relevant data about the kinetics and reaction properties of Bacillus AIs in D-tagatose production are still insufficient. Thus, in order to support further applications of these AIs, a comprehensive characterization of a Bacillus AI is needed. RESULTS: The coding gene (1422 bp) of Bacillus coagulans NL01 AI (BCAI) was cloned and overexpressed in the Escherichia coli BL21 (DE3) strain. The enzymatic property test showed that the optimal temperature and pH of BCAI were 60 degrees C and 7.5 respectively. The raw purified BCAI originally showed high activity in absence of outsourcing metallic ions and its thermostability did not change in a low concentration (0.5 mM) of Mn(2+) at temperatures from 70 degrees C to 90 degrees C. Besides these, the catalytic efficiencies (k cat/K m) for L-arabinose and D-galactose were 8.7 mM(-1) min(-1) and 1.0 mM(-1) min(-1) respectively. Under optimal conditions, the recombinant E. coli cell containing BCAI could convert 150 g L(-1) and 250 g L(-1) D-galactose to D-tagatose with attractive conversion rates of 32 % (32 h) and 27 % (48 h). CONCLUSIONS: In this study, a novel AI from B. coagulans NL01was cloned, purified and characterized. Compared with other reported AIs, this AI could retain high proportions of activity at a broader range of temperatures and was less dependent on metallic cofactors such as Mn(2+). Its substrate specificity was understood deeply by carrying out molecular modelling and docking studies. When the recombinant E. coli expressing the AI was used as a biocatalyst, D-tagatose could be produced efficiently in a simple one-pot biotransformation system. PMID- 27363439 TI - Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come. AB - Cancer is a leading cause of death in many countries around the world. However, the efficacy of current standard treatments for a variety of cancers is suboptimal. First, most cancer treatments lack specificity, meaning that these treatments affect both cancer cells and their normal counterparts. Second, many anticancer agents are highly toxic, and thus, limit their use in treatment. Third, a number of cytotoxic chemotherapeutics are highly hydrophobic, which limits their utility in cancer therapy. Finally, many chemotherapeutic agents exhibit short half-lives that curtail their efficacy. As a result of these deficiencies, many current treatments lead to side effects, noncompliance, and patient inconvenience due to difficulties in administration. However, the application of nanotechnology has led to the development of effective nanosized drug delivery systems known commonly as nanoparticles. Among these delivery systems, lipid-based nanoparticles, particularly liposomes, have shown to be quite effective at exhibiting the ability to: 1) improve the selectivity of cancer chemotherapeutic agents; 2) lower the cytotoxicity of anticancer drugs to normal tissues, and thus, reduce their toxic side effects; 3) increase the solubility of hydrophobic drugs; and 4) offer a prolonged and controlled release of agents. This review will discuss the current state of lipid-based nanoparticle research, including the development of liposomes for cancer therapy, different strategies for tumor targeting, liposomal formulation of various anticancer drugs that are commercially available, recent progress in liposome technology for the treatment of cancer, and the next generation of lipid-based nanoparticles. PMID- 27363470 TI - Effects of N-/C-Terminal Extra Tags on the Optimal Reaction Conditions, Activity, and Quaternary Structure of Bacillus thuringiensis Glucose 1-Dehydrogenase. AB - Glucose dehydrogenase (GDH) is an oxidoreductase enzyme and is used as a biocatalyst to regenerate NAD(P)H in reductase-mediated chiral synthesis reactions. In this study, the glucose 1-dehydrogenase B gene (gdhB) was cloned from Bacillus thuringiensis subsp. kurstaki, and wild-type (GDH-BTWT) and His tagged (GDH-BTN-His, GDH-BTC-His) enzymes were produced in Escherichia coli BL21 (DE3). All enzymes were produced in the soluble forms from E. coli. GDH-BTWT and GDH-BTN-His showed high specific enzymatic activities of 6.6 U/mg and 5.5 U/mg, respectively, whereas GDH-BTC-His showed a very low specific enzymatic activity of 0.020 U/mg. These results suggest that the intact C-terminal carboxyl group is important for GDH-BT activity. GDH-BTWT was stable up to 65 degrees C, whereas GDH-BTN-His and GDH-BTC-His were stable up to 45 degrees C. Gel permeation chromatography showed that GDH-BTWT is a dimer, whereas GDH-BTN-His and GDH-BTC His are monomeric. These results suggest that the intact N- and C-termini are required for GDH-BT to maintain thermostability and to form its dimer structure. The homology model of the GDH-BTWT single subunit was constructed based on the crystal structure of Bacillus megaterium GDH (PDB ID 3AY6), showing that GDH-BTWT has a Rossmann fold structure with its N- and C-termini located on the subunit surface, which suggests that His-tagging affected the native dimer structure. GDH BTWT and GDH-BTN-His regenerated NADPH in a yeast reductase-mediated chiral synthesis reaction, suggesting that these enzymes can be used as catalysts in fine-chemical and pharmaceutical industries. PMID- 27363471 TI - Enhancing the Thermal Resistance of a Novel Acidobacteria-Derived Phytase by Engineering of Disulfide Bridges. AB - A novel phytase of Acidobacteria was identified from a soil metagenome, cloned, overexpressed, and purified. It has low sequence similarity (<44%) to all the known phytases. At the optimum pH (2.5), the phytase shows an activity level of 1,792 MUmol/min/mg at physiological temperature (37 degrees C) and could retain 92% residual activity after 30 min, indicating the phytase is acidophilic and acidostable. However the phytase shows poor stability at high temperatures. To improve its thermal resistance, the enzyme was redesigned using Disulfide by Design 2.0, introducing four additional disulfide bridges. The half-life time of the engineered phytase at 60 degrees C and 80 degrees C, respectively, is 3.0* and 2.8* longer than the wild-type, and its activity and acidostability are not significantly affected. PMID- 27363472 TI - Analytical Applications of Nanomaterials in Monitoring Biological and Chemical Contaminants in Food. AB - The detection of food pathogens is an important aspect of food safety. A range of detection systems and new analytical materials have been developed to achieve fast, sensitive, and accurate monitoring of target pathogens. In this review, we summarize the characteristics of selected nanomaterials and their applications in food, and place focus on the monitoring of biological and chemical contaminants in food. The unique optical and electrical properties of nanomaterials, such as gold nanoparticles, nanorods, quantum dots, carbon nanotubes, graphenes, nanopores, and polydiacetylene nanovesicles, are closely associated with their dimensions, which are comparable in scale to those of targeted biomolecules. Furthermore, their optical and electrical properties are highly dependent on local environments, which make them promising materials for sensor development. The specificity and selectivity of analytical nanomaterials for target contaminants can be achieved by combining them with various biological entities, such as antibodies, oligonucleotides, aptamers, membrane proteins, and biological ligands. Examples of nanomaterial-based analytical systems are presented together with their limitations and associated developmental issues. PMID- 27363473 TI - Bacterial Overexpression and Denaturing Purification of VPS34-Binding Domain of Beclin 1. AB - As a scaffolding subunit of the PIK3C3/VPS34 complex, Beclin 1 recruits a variety of proteins to class III phosphatidylinositol-3-kinase (VPS34), resulting in the formation of a distinct PIK3C3/VPS34 complex with a specific function. Therefore, the investigation of a number of Beclin 1 domains required for the protein protein interactions will provide important clues to understand the PIK3C3/VPS34 complex, of which Beclin1-VPS34 interaction is the core unit. In the present study, we have designed a bacterial overexpression system for the Beclin 1 domain corresponding to VPS34 binding (Vps34-BD) and set up the denaturing purification protocol due to the massive aggregation of Vps34-BD in Escherichia coli. The expression and purification conditions determined in this study successfully provided soluble and functional Vps34-BD. PMID- 27363474 TI - A Comparison between Low- and High-Passage Strains of Human Cytomegalovirus. AB - To understand how human cytomegalovirus (HCMV) might change and evolve after reactivation, it is very important to understand how the nucleotide sequence of cultured HCMV changes after in vitro passaging in cell culture, and how these changes affect the genome of HCMV and the consequent variation in amino acid sequence. Strain JHC of HCMV was propagated in vitro for more than 40 passages and its biological and genetic changes were monitored. For each passage, real time PCR was performed in order to determine the genome copy number, and a plaque assay was employed to get virus infection titers. The infectious virus titers gradually increased with passaging in cell culture, whereas the number of virus genome copies remained relatively unchanged. A linear correlation was observed between the passage number and the log10 infectious virus titer per virus genome copy number. To understand the genetic basis underlying the increase in HCMV infectivity with increasing passage, the whole-genome DNA sequence of the high passage strain was determined and compared with the genome sequence of the low passage strain. Out of 100 mutations found in the high-passage strain, only two were located in an open reading frame. A G-T substitution in the RL13 gene resulted in a nonsense mutation and caused an early stop. A G-A substitution in the UL122 gene generated an S-F nonsynonymous mutation. The mutations in the RL13 and UL122 genes might be related to the increase in virus infectivity, although the role of the mutations found in noncoding regions could not be excluded. PMID- 27363475 TI - Alteration of Phospholipids during the Mitophagic Process in Lung Cancer Cells. AB - Matrix assisted laser desorption ionization (MALDI)-time of flight/mass spectrometry (TOF/MS) was applied to investigate alterations in phospholipids in mitophagic cancer cells. Several phospholipids, including phosphatidylcholines (PCs), sphingomyelins (SMs), and phosphatidylinositols (PIs), were successfully analyzed in control and mitophagy-induced H460 cells in the positive and negative ion modes. Principal component analysis was applied to differentiate the two groups. The upregulated and downregulated phospholipid species in the mitophagic cells were also represented in a heatmap. In the volcano plot (fold change > 1.3 and p value < 0.01), individual species of seven PCs, two SMs, and three PIs were selected as differentially regulated phospholipids. In particular, almost all the molecular species of PC, SM, and PI were downregulated in the mitophagic cells. Quantification of these lipids indicated that mitophagy induces altered metabolism of phospholipids. Therefore, phospholipid alterations during the mitophagic process of lung cancer cells were well characterized by MALDI-TOF/MS. PMID- 27363476 TI - Characteristics of the Molecular Epidemiology of CTX-M-Producing Escherichia coli Isolated from a Tertiary Hospital in Daejeon, Korea. AB - The aims of this study were to characterize the molecular epidemiological profiles of CTX-M-producing uropathogenic Escherichia coli isolates from a tertiary hospital in Daejeon, Korea, and to investigate the genetic diversity and compare the prevalence of sequence types (STs) in different areas. Extended spectrum beta-lactamase-producing E. coli strains isolated from urine were analyzed for CTX-M, integrons, and insertion sequence common regions (ISCRs) by PCR and sequencing. Multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), phylogenetic analysis, and rep-PCR were also used for molecular typing of the isolates. Of 80 CTX-M producers, 31 and 46 expressed CTX M-15 and CTX-M-14, respectively. MLST analysis indicated that the most prevalent ST was ST131 (n = 34, 42.5%), followed by ST38 (n = 22, 27.5%), ST405 (n = 8, 10.0%), and ST69 (n = 6, 7.5%). Most CTX-M producers harbored class 1 integrons. ST131 strains belonged to phylogenetic group B2 and showed identical rep-PCR patterns, whereas ST69, ST38, and ST405 strains belonged to phylogenetic group D; the ST38 and ST405 strains displayed the same rep-PCR pattern, respectively. ST131 and ST38 isolates showed 21 and 19 distinct types, respectively, by PFGE. In Daejeon, D-ST38 CTX-M-14 producers were relatively more prevalent than in other countries and Korean cities. Our results indicate that CTX-M-producing E. coli isolates belonged mostly to ST131 or ST38 and were more related to hospital onset than to community-onset infections and that the blaCTX-M gene may vary according to the ST. PMID- 27363441 TI - The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis. AB - The nucleus accumbens is a major input structure of the basal ganglia and integrates information from cortical and limbic structures to mediate goal directed behaviors. Chronic exposure to several classes of drugs of abuse disrupts plasticity in this region, allowing drug-associated cues to engender a pathologic motivation for drug seeking. A number of alterations in glutamatergic transmission occur within the nucleus accumbens after withdrawal from chronic drug exposure. These drug-induced neuroadaptations serve as the molecular basis for relapse vulnerability. In this review, we focus on the role that glutamate signal transduction in the nucleus accumbens plays in addiction-related behaviors. First, we explore the nucleus accumbens, including the cell types and neuronal populations present as well as afferent and efferent connections. Next we discuss rodent models of addiction and assess the viability of these models for testing candidate pharmacotherapies for the prevention of relapse. Then we provide a review of the literature describing how synaptic plasticity in the accumbens is altered after exposure to drugs of abuse and withdrawal and also how pharmacological manipulation of glutamate systems in the accumbens can inhibit drug seeking in the laboratory setting. Finally, we examine results from clinical trials in which pharmacotherapies designed to manipulate glutamate systems have been effective in treating relapse in human patients. Further elucidation of how drugs of abuse alter glutamatergic plasticity within the accumbens will be necessary for the development of new therapeutics for the treatment of addiction across all classes of addictive substances. PMID- 27363477 TI - The N-Terminal alpha-Helix Domain of Pseudomonas aeruginosa Lipoxygenase Is Required for Its Soluble Expression in Escherichia coli but Not for Catalysis. AB - Lipoxygenase (LOX) is an industrial enzyme with wide applications in food and pharmaceutical industries. The available structure information indicates that eukaryotic LOXs consist of N terminus beta-barrel and C terminus catalytic domains. However, the latest crystal structure of Pseudomonas aeruginosa LOX shows it is significantly different from those of eukaryotic LOXs, including the N-terminal helix domain. In this paper, the functions of this N-terminal helix domain in the soluble expression and catalysis of P. aeruginosa LOX were analyzed. Genetic truncation of this helix domain resulted in an insoluble P. aeruginosa LOX mutant. The active C-terminal domain was obtained by dispase digestion of the P. aeruginosa LOX derivative containing the genetically introduced dispase recognition sites. This functional C-terminal domain showed raised substrate affinity but reduced catalytic activity and thermostability. Crystal structure analyses demonstrate that the broken polar contacts connecting the two domains and the exposed hydrophobic substrate binding pocket may contribute to the insoluble expression of the C terminus domain and the changes in the enzyme properties. Our data suggest that the N terminus domain of P. aeruginosa LOX is required for its soluble expression in E. coli, which is different from that of the eukaryotic LOXs. Besides this, this N-terminal domain is not necessary for catalysis but shows positive effects on the enzyme properties. The results presented here provide new and valuable information on the functions of the N terminus helix domain of P. aeruginosa LOX and further improvement of its enzyme properties by molecular modification. PMID- 27363478 TI - Inhibition of the Calcineurin Pathway by Two Flavonoids Isolated from Miliusa sinensis Finet & Gagnep. AB - In order to discover plant-derived signaling pathway inhibitors with antifungal properties, a two-component screening system utilizing the calcineurin and Hog1 mitogen-activated protein kinase pathways responsible for the virulence networks of Cryptococcus neoformans was employed, owing to the counter-regulatory actions of these pathways. Of the 1,000 plant extracts tested, two bioactive compounds from Miliusa sinensis were found to act specifically on the calcineurin pathway of C. neoformans. These compounds, identified as pashanone and 5-hydroxy-6,7 dimethoxyflavanone, exhibited potent antifungal activities against various human pathogenic fungi with minimum inhibitory concentration values ranging from 4.0 to >128 MUg/ml. PMID- 27363479 TI - Recombinant Glargine Insulin Production Process Using Escherichia coli. AB - Glargine insulin is a long-acting insulin analog that helps blood glucose maintenance in patients with diabetes. We constructed the pPT-GI vector to express prepeptide glargine insulin when transformed into Escherichia coli JM109. The transformed E. coli cells were cultured by fed-batch fermentation. The final dry cell mass was 18 g/l. The prepeptide glargine insulin was 38.52% of the total protein. It was expressed as an inclusion body and then refolded to recover the biological activity. To convert the prepeptide into glargine insulin, citraconylation and trypsin cleavage were performed. Using citraconylation, the yield of enzymatic conversion for glargine insulin increased by 3.2-fold compared with that without citraconylation. After the enzyme reaction, active glargine insulin was purified by two types of chromatography (ion-exchange chromatography and reverse-phase chromatography). We obtained recombinant human glargine insulin at 98.11% purity and verified that it is equal to the standard of human glargine insulin, based on High-performance liquid chromatography analysis and Matrix assisted laser desorption/ionization Time-of-Flight Mass Spectrometry. We thus established a production process for high-purity recombinant human glargine insulin and a method to block Arg (B31)-insulin formation. This established process for recombinant human glargine insulin may be a model process for the production of other human insulin analogs. PMID- 27363480 TI - Irradiation-induced degradation of PTB7 investigated by valence band and S 2p photoelectron spectroscopy. AB - Monochromatic radiation with known absolute radiant power from an undulator at the electron storage ring Metrology Light Source (MLS) was used to irradiate PTB7 (a thieno[3, 4-b]thiophene-alt-benzodithiophene polymer) thin films at wavelengths (photon energies) of 185 nm (6.70 eV), 220 nm (5.64 eV), 300 nm (4.13 eV), 320 nm (3.88 eV), 356 nm (3.48 eV) and 675 nm (1.84 eV) under ultra-high vacuum conditions for the investigation of radiation-induced degradation effects. The characterization of the thin films is focused at ultraviolet photoelectron spectroscopy (UPS) of valence bands and is complemented by S 2p x-ray photoelectron spectroscopy (S 2p XPS) before and after the irradiation procedure. The radiant exposure was determined for each irradiation by means of photodiodes traceably calibrated to the international system of units SI. The valence band spectra show the strongest changes for the shortest wavelengths and no degradation effect at 356 nm and 675 nm even with the highest radiant exposure applied. In the spectral range where the Sun appears bright on the Earth's surface, no degradation effects are observed. PMID- 27363481 TI - Dual Nuclear/Fluorescence Imaging Potantial of Zinc(II) Phthalocyanine in MIA PaCa-2 Cell Line. AB - BACKGROUND AND OBJECTIVE: Pancreatic cancer is very common and difficult to diagnose in early stage. Imaging systems for diagnosing cancer have many disadvantages. However, combining different imaging modalities offers synergistic advantages. Optical imaging is the most multidirectional and widely used imaging modality in both clinical practice and research. METHODS: In present study, Zinc(II) phthalocyanine [Zn(II)Pc] was synthesized, labeled with iodine- 131 and in vitro study was carried out. The intracellular uptake studies of radiolabeled Zn(II)Pc were performed in WI-38 [ATCC CCL-75TM, tissue: human fibroblast lung] and MIA PaCa-2 [ATCC CRL-1420TM, tissue: human epithelial pancreas carcinoma] cell lines. RESULTS: The intracellular uptake efficiency of radiolabeled Zn(II)Pc in MIA PaCa-2 cells was determined two times higher than WI-38 cells. Also, fluorescence imaging (FI) efficiency of synthesized Zn(II)Pc was investigated in MIA PaCa-2 cells and significant uptake was observed. CONCLUSION: Zn(II)Pc might be used as a new agent for dual fluorescence/nuclear imaging for pancreatic cancer. PMID- 27363482 TI - Trajectories of Suicidal Ideation in People Seeking Web-Based Help for Suicidality: Secondary Analysis of a Dutch Randomized Controlled Trial. AB - BACKGROUND: Suicidal ideation (SI) is a common mental health problem. Variability in intensity of SI over time has been linked to suicidal behavior, yet little is known about the temporal course of SI. OBJECTIVE: The primary aim was to identify prototypical trajectories of SI in the general population and, secondarily, to examine whether receiving Web-based self-help for SI, psychiatric symptoms, or sociodemographics predicted membership in the identified SI trajectories. METHODS: We enrolled 236 people, from the general Dutch population seeking Web based help for SI, in a randomized controlled trial comparing a Web-based self help for SI group with a control group. We assessed participants at inclusion and at 2, 4, and 6 weeks. The Beck Scale for Suicide Ideation was applied at all assessments and was included in latent growth mixture modeling analysis to empirically identify trajectories. RESULTS: We identified 4 SI trajectories. The high stable trajectory represented 51.7% (122/236) of participants and was characterized by constant high level of SI. The high decreasing trajectory (50/236, 21.2%) consisted of people with a high baseline SI score followed by a gradual decrease to a very low score. The third trajectory, high increasing (12/236, 5.1%), also had high initial SI score, followed by an increase to the highest level of SI at 6 weeks. The fourth trajectory, low stable (52/236, 22.0%) had a constant low level of SI. Previous attempted suicide and having received Web-based self-help for SI predicted membership in the high decreasing trajectory. CONCLUSIONS: Many adults experience high persisting levels of SI, though results encouragingly indicate that receiving Web-based self-help for SI increased membership in a decreasing trajectory of SI. PMID- 27363483 TI - The genus Hymenocrater: a comprehensive review. AB - CONTEXT: The genus Hymenocrater Fisch. et Mey. (Lamiaceae) contains over 21 species in the world. Some species have been used in folk medicine around the world. The present review comprises the ethnopharmacological, phytochemical and therapeutic potential of various species of Hymenocrater. OBJECTIVE: This review brings together most of the available scientific research regarding the genus Hymenocrater. Through this review, the authors hope to attract the attention of natural product researchers throughout the world to focus on the unexplored potential of Hymenocrater species. METHODS: This review has been compiled using references from major databases such as Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, ScienceDirect, SciFinder, Google Scholar, Scopus, PubMed, Springer Link and books, without limiting the dates of publication. General web searches were also carried out using Google and Yahoo search engines by applying some related search terms (e.g., Hymenocrater spp., phytochemical, pharmacological, extract, essential oil and traditional uses). The articles related to agriculture, ecology, and synthetic works and those using languages other than English or Persian have been excluded. RESULTS: The genus Hymenocrater contains essential oil. Flavonoids, phenolic acids and terpenoids are important constituents of this genus. The pharmacological studies confirmed that the species of the genus Hymenocrater showed antimicrobial, antiparasitic, antioxidant, anticancer and antidiabetic activities. CONCLUSION: This review discusses the current knowledge of Hymenocrater species that review therapeutic potential, especially their effects on the cancer cells and gaps offering opportunities for future research. PMID- 27363484 TI - Proteomics analysis of vesicles isolated from plasma and urine of prostate cancer patients using a multiplex, aptamer-based protein array. AB - Proteomics analysis of biofluid-derived vesicles holds enormous potential for discovering non-invasive disease markers. Obtaining vesicles of sufficient quality and quantity for profiling studies has, however, been a major problem, as samples are often replete with co-isolated material that can interfere with the identification of genuine low abundance, vesicle components. Here, we used a combination of ultracentrifugation and size-exclusion chromatography to isolate and analyse vesicles of plasma or urine origin. We describe a sample-handling workflow that gives reproducible, quality vesicle isolations sufficient for subsequent protein profiling. Using a semi-quantitative aptamer-based protein array, we identified around 1,000 proteins, of which almost 400 were present at comparable quantities in plasma versus urine vesicles. Significant differences were, however, apparent with elements like HSP90, integrin alphaVbeta5 and Contactin-1 more prevalent in urinary vesicles, while hepatocyte growth factor activator, prostate-specific antigen-antichymotrypsin complex and many others were more abundant in plasma vesicles. This was also applied to a small set of specimens collected from men with metastatic prostate cancer, highlighting several proteins with the potential to indicate treatment refractory disease. The study provides a practical platform for furthering protein profiling of vesicles in prostate cancer, and, hopefully, many other disease scenarios. PMID- 27363485 TI - Catalysts of DNA Strand Cleavage at Apurinic/Apyrimidinic Sites. AB - Apurinic/apyrimidinic (AP) sites are constantly formed in cellular DNA due to instability of the glycosidic bond, particularly at purines and various oxidized, alkylated, or otherwise damaged nucleobases. AP sites are also generated by DNA glycosylases that initiate DNA base excision repair. These lesions represent a significant block to DNA replication and are extremely mutagenic. Some DNA glycosylases possess AP lyase activities that nick the DNA strand at the deoxyribose moiety via a beta- or beta,delta-elimination reaction. Various amines can incise AP sites via a similar mechanism, but this non-enzymatic cleavage typically requires high reagent concentrations. Herein, we describe a new class of small molecules that function at low micromolar concentrations as both beta- and beta,delta-elimination catalysts at AP sites. Structure-activity relationships have established several characteristics that appear to be necessary for the formation of an iminium ion intermediate that self-catalyzes the elimination at the deoxyribose ring. PMID- 27363486 TI - Natural variation of root exudates in Arabidopsis thaliana-linking metabolomic and genomic data. AB - Many metabolomics studies focus on aboveground parts of the plant, while metabolism within roots and the chemical composition of the rhizosphere, as influenced by exudation, are not deeply investigated. In this study, we analysed exudate metabolic patterns of Arabidopsis thaliana and their variation in genetically diverse accessions. For this project, we used the 19 parental accessions of the Arabidopsis MAGIC collection. Plants were grown in a hydroponic system, their exudates were harvested before bolting and subjected to UPLC/ESI QTOF-MS analysis. Metabolite profiles were analysed together with the genome sequence information. Our study uncovered distinct metabolite profiles for root exudates of the 19 accessions. Hierarchical clustering revealed similarities in the exudate metabolite profiles, which were partly reflected by the genetic distances. An association of metabolite absence with nonsense mutations was detected for the biosynthetic pathways of an indolic glucosinolate hydrolysis product, a hydroxycinnamic acid amine and a flavonoid triglycoside. Consequently, a direct link between metabolic phenotype and genotype was detected without using segregating populations. Moreover, genomics can help to identify biosynthetic enzymes in metabolomics experiments. Our study elucidates the chemical composition of the rhizosphere and its natural variation in A. thaliana, which is important for the attraction and shaping of microbial communities. PMID- 27363488 TI - CRISP-ID: decoding CRISPR mediated indels by Sanger sequencing. AB - The advent of next generation gene editing technologies has revolutionized the fields of genome engineering in allowing the generation of gene knockout models and functional gene analysis. However, the screening of resultant clones remains challenging due to the simultaneous presence of different indels. Here, we present CRISP-ID, a web application which uses a unique algorithm for genotyping up to three alleles from a single Sanger sequencing trace, providing a robust and readily accessible platform to directly identify indels and significantly speed up the characterization of clones. PMID- 27363487 TI - Important role of N108 residue in binding of bovine foamy virus transactivator Tas to viral promoters. AB - BACKGROUND: Bovine foamy virus (BFV) encodes the transactivator BTas, which enhances viral gene transcription by binding to the long terminal repeat promoter and the internal promoter. In this study, we investigated the different replication capacities of two similar BFV full-length DNA clones, pBS-BFV-Y and pBS-BFV-B. RESULTS: Here, functional analysis of several chimeric clones revealed a major role for the C-terminal region of the viral genome in causing this difference. Furthermore, BTas-B, which is located in this C-terminal region, exhibited a 20-fold higher transactivation activity than BTas-Y. Sequence alignment showed that these two sequences differ only at amino acid 108, with BTas-B containing N108 and BTas-Y containing D108 at this position. Results of mutagenesis studies demonstrated that residue N108 is important for BTas binding to viral promoters. In addition, the N108D mutation in pBS-BFV-B reduced the viral replication capacity by about 1.5-fold. CONCLUSIONS: Our results suggest that residue N108 is important for BTas binding to BFV promoters and has a major role in BFV replication. These findings not only advances our understanding of the transactivation mechanism of BTas, but they also highlight the importance of certain sequence polymorphisms in modulating the replication capacity of isolated BFV clones. PMID- 27363489 TI - GLP-1 analogues for neuroprotection after out-of-hospital cardiac arrest: study protocol for a randomized controlled trial. AB - BACKGROUND: Attenuating the neurological damage occurring after out-of-hospital cardiac arrest is an ongoing research effort. This dual-centre study investigates the neuroprotective effects of the glucagon-like-peptide-1 analogue Exenatide administered within 4 hours from the return of spontaneous circulation to comatose patients resuscitated from out-of-hospital cardiac arrest. METHODS/DESIGN: This pilot study will randomize a total of 120 unconscious patients with sustained return of spontaneous circulation after out-of-hospital cardiac arrest undergoing targeted temperature management in a blinded one-to-one fashion to a 6-hour and 15-minute infusion of either Exenatide or placebo. Patients are eligible for inclusion if resuscitated from cardiac arrest with randomization from 20 minutes to 240 minutes after return of spontaneous circulation. The co-primary endpoint is feasibility, defined as the initiation of treatment within the inclusion window in more than 90 % of participants, and efficacy, defined as the area under the neuron-specific enolase curve from 0 to 72 hours after admission. Secondary endpoints include all-cause mortality at 30 days and Cerebral Performance Category as well as a modified Rankin Score at 180 days. The study has been approved by the Danish National Board of Health and the local Ethics Committee and is monitored by Good Clinical Practice units. The study is currently enrolling. DISCUSSION: This paper presents the methods and planned statistical analyses used in the GLP-1 trial and aims to minimize bias and data-driven reporting of results. TRIAL REGISTRATION: 1) Danish National Board of Health, EudraCT 2013-004311-45. Registered on 25 March 2014. 2) Videnskabsetisk komite C, Region Hovedstaden, No. 45728. Registered on 29 January 2014. 3) Clinicaltrial.gov, NCT02442791 . Registered on 25 of January 2015. PMID- 27363490 TI - Exploring chromosomal abnormalities and genetic changes in uterine smooth muscle tumors. AB - Smooth muscle tumors of the uterus are a diagnostically challenging group of tumors. Molecular surrogate markers reliably distinguishing between benign and malignant tumors are not available. Therefore, the diagnosis is based on morphologic criteria. The aim was to investigate a well-characterized group of challenging uterine smooth muscle tumors consisting of 20 leiomyomas, 13 leiomyomas with bizarre nuclei, and 14 leiomyosarcomas for copy number alterations, MED12 mutations and FH deletions to search for potential diagnostically useful surrogate markers. MED12 mutations were detected in 47, 15, and 25% of leiomyomas, leiomyomas with bizarre nuclei and leiomyosarcomas, respectively. MED12 mutations in leiomyomas with bizarre nuclei were detected outside the hotspot region. FH-deletions were seen in 27, 30.8, and 25% of leiomyomas, leiomyomas with bizarre nuclei and leiomyosarcomas, respectively. By using copy number alteration profiling a clear separation of leiomyomas, leiomyomas with bizarre nuclei and leiomyosarcomas could not be observed. Copy number alterations revealed clear genetic similarities between leiomyomas with bizarre nuclei and leiomyosarcomas. Leiomyosarcomas showed a similar pattern of gains and losses as leiomyomas with bizarre nuclei, with additional copy number alterations and more homozygous losses and high-level amplifications compared to leiomyomas with bizarre nuclei. In conclusion, this study demonstrates that known FH-deletions, a recurrent molecular change in leiomyomas, occur in morphologically challenging variants of leiomyomas, leiomyomas with bizarre nuclei and leiomyosarcomas. Although MED12 mutations are common in leiomyomas, they infrequently occur in leiomyomas with bizarre nuclei and leiomyosarcomas. The genetic similarities between leiomyomas with bizarre nuclei and leiomyosarcomas raise the intriguing possibility that uterine leiomyomas with bizarre nuclei and leiomyosarcomas are closely related and challenge the traditional concept that leiomyoma with bizarre nuclei is a tumor with just marked 'degenerative' cellular changes. These findings support the hypothesis that tumor progression within uterine smooth muscle tumors might occur. PMID- 27363491 TI - Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer: results of the ring studies of the international immuno-oncology biomarker working group. AB - Multiple independent studies have shown that tumor-infiltrating lymphocytes (TIL) are prognostic in breast cancer with potential relevance for response to immune checkpoint inhibitor therapy. Although many groups are currently evaluating TIL, there is no standardized system for diagnostic applications. This study reports the results of two ring studies investigating TIL conducted by the International Working Group on Immuno-oncology Biomarkers. The study aim was to determine the intraclass correlation coefficient (ICC) for evaluation of TIL by different pathologists. A total of 120 slides were evaluated by a large group of pathologists with a web-based system in ring study 1 and a more advanced software system in ring study 2 that included an integrated feedback with standardized reference images. The predefined aim for successful ring studies 1 and 2 was an ICC above 0.7 (lower limit of 95% confidence interval (CI)). In ring study 1 the prespecified endpoint was not reached (ICC: 0.70; 95% CI: 0.62-0.78). On the basis of an analysis of sources of variation, we developed a more advanced digital image evaluation system for ring study 2, which improved the ICC to 0.89 (95% CI: 0.85-0.92). The Fleiss' kappa value for <60 vs >=60% TIL improved from 0.45 (ring study 1) to 0.63 in RS2 and the mean concordance improved from 88 to 92%. This large international standardization project shows that reproducible evaluation of TIL is feasible in breast cancer. This opens the way for standardized reporting of tumor immunological parameters in clinical studies and diagnostic practice. The software-guided image evaluation approach used in ring study 2 may be of value as a tool for evaluation of TIL in clinical trials and diagnostic practice. The experience gained from this approach might be applicable to the standardization of other diagnostic parameters in histopathology. PMID- 27363494 TI - Influence of Cononsolvency on the Aggregation of Tertiary Butyl Alcohol in Methanol-Water Mixtures. AB - The term cononsolvency has been used to describe a situation in which a polymer is less soluble (and so is more likely to collapse and aggregate) in a mixture of two cosolvents than it is in either one of the pure solvents. Thus, cononsolvency is closely related to the suppression of protein denaturation by stabilizing osmolytes. Here, we show that cononsolvency behavior can also influence the aggregation of tertiary butyl alcohol in mixtures of water and methanol, as demonstrated using both Raman multivariate curve resolution spectroscopy and molecular dynamics simulations. Our results imply that cononsolvency results from the cosolvent-mediated enhancement of the attractive (solvophobic) mean force between nonpolar groups, driven by preferential solvation of the aggregates, in keeping with Wyman-Tanford theory. PMID- 27363493 TI - Role for the thromboxane A2 receptor beta-isoform in the pathogenesis of intrauterine growth restriction. AB - Intrauterine growth restriction (IUGR) is a pathology of pregnancy that results in failure of the fetus to reach its genetically determined growth potential. In developed nations the most common cause of IUGR is impaired placentation resulting from poor trophoblast function, which reduces blood flow to the fetoplacental unit, promotes hypoxia and enhances production of bioactive lipids (TXA2 and isoprostanes) which act through the thromboxane receptor (TP). TP activation has been implicated as a pathogenic factor in pregnancy complications, including IUGR; however, the role of TP isoforms during pregnancy is poorly defined. We have determined that expression of the human-specific isoform of TP (TPbeta) is increased in placentae from IUGR pregnancies, compared to healthy pregnancies. Overexpression of TPalpha enhanced trophoblast proliferation and syncytialisation. Conversely, TPbeta attenuated these functions and inhibited migration. Expression of the TPbeta transgene in mice resulted in growth restricted pups and placentae with poor syncytialisation and diminished growth characteristics. Together our data indicate that expression of TPalpha mediates normal placentation; however, TPbeta impairs placentation, and promotes the development of IUGR, and represents an underappreciated pathogenic factor in humans. PMID- 27363495 TI - Light-sheet microscopy for everyone? Experience of building an OpenSPIM to study flatworm development. AB - BACKGROUND: Selective plane illumination microscopy (SPIM a type of light-sheet microscopy) involves focusing a thin sheet of laser light through a specimen at right angles to the objective lens. As only the thin section of the specimen at the focal plane of the lens is illuminated, out of focus light is naturally absent and toxicity due to light (phototoxicity) is greatly reduced enabling longer term live imaging. OpenSPIM is an open access platform (Pitrone et al. 2013 and OpenSPIM.org) created to give new users step-by-step instructions on building a basic configuration of a SPIM microscope, which can in principle be adapted and upgraded to each laboratory's own requirements and budget. Here we describe our own experience with the process of designing, building, configuring and using an OpenSPIM for our research into the early development of the polyclad flatworm Maritigrella crozieri - a non-model animal. RESULTS: Our OpenSPIM builds on the standard design with the addition of two colour laser illumination for simultaneous detection of two probes/molecules and dual sided illumination, which provides more even signal intensity across a specimen. Our OpenSPIM provides high resolution 3d images and time lapse recordings, and we demonstrate the use of two colour lasers and the benefits of two color dual-sided imaging. We used our microscope to study the development of the embryo of the polyclad flatworm M. crozieri. The capabilities of our microscope are demonstrated by our ability to record the stereotypical spiral cleavage pattern of M. crozieri with high-speed multi-view time lapse imaging. 3D and 4D (3D + time) reconstruction of early development from these data is possible using image registration and deconvolution tools provided as part of the open source Fiji platform. We discuss our findings on the pros and cons of a self built microscope. CONCLUSIONS: We conclude that home-built microscopes, such as an OpenSPIM, together with the available open source software, such as MicroManager and Fiji, make SPIM accessible to anyone interested in having continuous access to their own light sheet microscope. However, building an OpenSPIM is not without challenges and an open access microscope is a worthwhile, if significant, investment of time and money. Multi-view 4D microscopy is more challenging than we had expected. We hope that our experience gained during this project will help future OpenSPIM users with similar ambitions. PMID- 27363492 TI - Diagnostic and predictive biomarkers for lymphoma diagnosis and treatment in the era of precision medicine. AB - Lymphomas are a group of hematological malignancies derived from lymphocytes. Lymphomas are clinically and biologically heterogeneous and have overlapping diagnostic features. With the advance of new technologies and the application of efficient and feasible detection platforms, an unprecedented number of novel biomarkers have been discovered or are under investigation at the genetic, epigenetic, and protein level as well as the tumor microenvironment. These biomarkers have enabled new clinical and pathological insights into the mechanisms underlying lymphomagenesis and also have facilitated improvements in the diagnostic workup, sub-classification, outcome stratification, and personalized therapy for lymphoma patients. However, integrating these biomarkers into clinical practice effectively and precisely in daily practice is challenging. More in-depth studies are required to further validate these novel biomarkers and to assess other parameters that can affect the reproducibility of these biomarkers such as the selection of detection methods, biological reagents, interpretation of data, and cost efficiency. Despite these challenges, there are many reasons to be optimistic that novel biomarkers will facilitate better algorithms and strategies as we enter a new era of precision medicine to better refine diagnosis, prognostication, and rational treatment design for patients with lymphomas. PMID- 27363497 TI - The feasibility of introducing an adult safeguarding measure for inclusion in the Adult Social Care Outcomes Framework (ASCOF): findings from a pilot study. AB - BACKGROUND: There are currently no national measures in England reporting the experiences of people who have been involved with adult safeguarding services following concerns that they may be at risk of abuse or neglect. The Health and Social Care Information Centre (HSCIC) aimed to develop a new adult safeguarding outcome measure (survey) for local authorities (LAs) that could be added to the Adult Social Care Outcomes Framework (ASCOF). The ASCOF is a national collection of social care outcomes performance indicators collected from the perspective of people receiving partial or total funding from a LA for care services. METHODS: An outcome measure (a face-to-face interview based survey consisting of 7 questions) was piloted in 40 LAs with 382 adults at risk (or their representative) who had been the subject of a safeguarding investigation. The aim was to investigate the feasibility of the survey in three domains: i) if a statistically representative sample of adults at risk (or their family, friend, carer or advocate) could be recruited; ii) analysis of survey responses and its acceptability to participants iii) feedback from LAs about the survey's administration. RESULTS AND DISCUSSION: Overall the survey results met statistical confidence; however the individual results for adults at risk did not, due to the high proportion of representatives who responded because adults at risk were unable. Responses to the survey were generally positive; 72 % of participants felt that the help received during the safeguarding investigation had made them or the adult at risk (if reporting as a proxy) feel 'quite a bit' or 'a lot safer'. These results are the most robust data collected in England on the perspectives of adults at risk and their representatives on safeguarding services. Participants reported they appreciated being asked for feedback. LAs suggested survey administration improvements. CONCLUSIONS: This survey is one way LAs can meet their new legal requirement under the Care Act 2014 to 'seek feedback' from adults at risk about adult safeguarding services. The survey findings provide the first robust evidence that safeguarding services in the main meet their goals of promoting feelings of safety among adults at risk. PMID- 27363496 TI - Prognostic values of four Notch receptor mRNA expression in gastric cancer. AB - Notch ligands and receptors are frequently deregulated in several human malignancies including gastric cancer. The activation of Notch signaling has been reported to contribute to gastric carcinogenesis and progression. However, the prognostic roles of individual Notch receptors in gastric cancer patients remain elusive. In the current study, we accessed the prognostic roles of four Notch receptors, Notch 1-4, in gastric cancer patients through "The Kaplan-Meier plotter" (KM plotter) database, in which updated gene expression data and survival information include a total of 876 gastric cancer patients. All four Notch receptors' high mRNA expression was found to be correlated to worsen overall survival (OS) for all gastric cancer patients followed for 20 years. We further accessed the prognostic roles of individual Notch receptors in different clinicopathological features using Lauren classification, pathological grades, clinical grades, HER2 status and different choices of treatments of gastric cancer patients. These results indicate that there are critical prognostic values of the four Notch receptors in gastric cancer. This information will be useful for better understanding of the heterogeneity and complexity in the molecular biology of gastric cancer and to develop tools to more accurately predict their prognosis. PMID- 27363498 TI - The mentor's role. PMID- 27363499 TI - Measuring medical students' empathy using direct verbal expressions. AB - PURPOSE: Empathy is an important trait in physicians and a key element in the physician-patient relationship. Accordingly, one of the goals in medical education is developing empathy in students. We attempted to practically assess medical students' empathy through their direct verbal expressions. METHODS: The medical students' empathy was measured using the modified Pencil-and-Paper Empathy Rating Test by Winefield and Chur-Hansen (2001). The students took 15 minutes or so to complete the scale, and it was then scored by one of two trained evaluators (0 to 4 points for each item, for a total score of 40). The subjects were 605 medical students, and the data were analyzed using descriptive analysis, independent t-test, and one-way analysis of variance in SPSS version 21.0. RESULTS: The students' empathy scores were low (mean, 12.13; standard deviation, 2.55); their most common responses (78.6%) registered as non-empathetic. Differences in empathy were observed by gender (female students>male students; t= 5.068, p<0.001), school system (medical school>medical college; t=-1.935, p=0.053), and academic level (pre-medical 1 year < other years; t=-4.050, p<0.001). CONCLUSION: Our findings lead us to the significant conclusion that there is the need for empathy enhancement training programs with practical content. PMID- 27363500 TI - Course-embedded assessment in Korean nursing baccalaureate education. AB - PURPOSE: This study aimed to evaluate the program outcome in nursing baccalaureate in Korea. The analysis based on course embedded assessment. The concrete objectives were establishment of program outcome assessment, confirmation of student competency through weighting of program outcomes, and using the results of the evaluation in the circular feedback process in a nursing school in Korea. METHODS: This study was conducted with a nursing education curriculum in a Korean nursing school. Data were collected through 28 students' program outcome measurement from January 2013 to December 2014. Data were analyzed using a pairwise comparison method and analytic hierarchy process. RESULTS: There were 1 to 3 direct and indirect assessment tools and for each program outcomes and each tool had measurable rubrics. There were 1 to 3 direct assessment tools for each program outcome, and each tool had measurable rubrics. This model derived rank of program outcomes from "care integration" to "global perception" through weight calculation. All direct assessment results were over 70%. The indirect assessment results were over the cutoff except for program outcomes 4 and 7. CONCLUSION: Each step of course embedded assessment was adaptive in nursing program outcome measure. The achievement of learning outcome provided reasonable tools for faculty and students. PMID- 27363501 TI - Influences of faculty evaluating system on educational performance of medical school faculty. AB - PURPOSE: The promotion of educators is challenged by the lack of accepted standards to evaluate the quality and impact of educational activities. Traditionally, promotion is related to research productivity. This study developed an evaluation tool for educational performance of medical school faculty using educator portfolios (EPs). METHODS: Design principles and quantitative items for EPs were developed in a consensus workshop. These principles were tested in a simulation and revised based on feedback. The changes of total educational activities following introduction of the system were analyzed. RESULTS: A total of 71% faculty members answered the simulation of the system and the score distributed widely (mean+/-standard deviation, 65.43+/ 68.64). The introduction of new system significantly increased the total educational activities, especially in assistant professors. CONCLUSION: The authors offer comprehensive and practical tool for enhancing educational participation of faculty members. Further research for development of qualitative evaluation systems is needed. PMID- 27363502 TI - A qualitative study on physicians' perceptions of specialty characteristics. AB - PURPOSE: There has been limited research on physicians' perceptions of the specialty characteristics that are needed to sustain a successful career in medical specialties in Korea. Medical Specialty Preference Inventory in the United States or SCI59 (specialty choice inventory) in the United Kingdom are implemented to help medical students plan their careers. The purpose of this study was to explore the characteristics of the major specialties in Korea. METHODS: Twelve physicians from different specialties participated in an exploratory study consisting of qualitative interviews about the personal ability and emotional characteristics and job attributes of each specialty. The collected data were analysed with content analysis methods. RESULTS: Twelve codes were extracted for ability & skill attributes, 23 codes for emotion & attitude attributes, and 12 codes for job attributes. Each specialty shows a different profile in terms of its characteristic attributes. CONCLUSION: The findings have implications for the design of career planning programs for medical students. PMID- 27363503 TI - Students' perception of the educational environment in medical college: a study based on DREEM questionnaire. AB - PURPOSE: The educational environment (EE) plays a very important role in effective student learning. The Dundee Ready Education Environment Measure (DREEM) is a validated tool to assess the EE. This study aimed to collect baseline information about our medical student's perception of the EE, and to identify areas of strengths and weaknesses as well as scope for improvements in the current EE. METHODS: Medical students and interns were included in this cross sectional study. The DREEM questionnaire was used to measure students' perceptions about the EE, which has five domains: students' perceptions of learning; students' perceptions of teachers; students' academic self-perceptions; students' perceptions of atmosphere; and students' social self-perceptions. Students were asked to respond using a 5-point Likert-type scale. Data was analyzed using suitable tests and statistical significance was set at p<0.05. RESULTS: The mean global DREEM score was 123/200. All students had more positive than negative academic self-perception (21.24/32), perception of atmosphere (29.21/48), and perception of learning (28.99/48), while their social self perception (17.48/28) was not too bad and perception of teachers (26.71/44) moved in the right direction. The fifth semester students perceived EE more positively than other semester students. CONCLUSION: The present study revealed that all students perceived their EE positively. The positive points were that teachers were knowledgeable, that students had good friends, and they were confident about passing their exams. Problem areas observed were authoritarian teachers, overemphasis on factual learning, overly teacher-centered teaching, teachers getting angry, and the need for a support system for stressed students. PMID- 27363504 TI - A Proposed Serum Calprotectin IgG Cut-Off Level for Diagnosing Inflammatory Arthritis. AB - BACKGROUND: The identification and validation of soluble markers provide significant opportunities for managing patients with rheumatic diseases, and calprotectin may be an alternative laboratory biomarker of inflammatory rheumatoid arthritis (RA) and psoriatic arthritis (PsA) even though its levels may vary considerably. The aim of this study was to propose a calprotectin cut off value that would be useful for distinguishing patients with inflammatory arthritis or noninflammatory arthritis (NIA) in clinical practice. METHODS: A commercial enzyme-linked immunosorbent assay was used to measure serum calprotectin levels in patients with RA, ankylosing spondylitis (AS), PsA and controls with NIA. All of the patients had been treated with biological disease modifying anti-rheumatic drugs (DMARDs) for about 12 months after previous failure on conventional DMARDs. RESULTS: Receiver operating characteristic (ROC) analysis showed that serum calprotectin levels significantly differentiated the samples of the patients with inflammatory rheumatic disease from those of the controls. A serum calprotectin level of > 0.9 MUg/mL (the optimal predictive cut off value in the ROC analysis) had a sensitivity of 95.3%, a specificity of 82.2%, a positive likelihood ratio (LR) of 5.35 and a negative LR of 0.057. CONCLUSIONS: Our findings suggest that serum calprotectin levels are useful in clinical practice to distinguish patients with inflammatory arthritis and NIA. Further studies of a larger population are suggested. PMID- 27363505 TI - Assessing the negative impact of phenyl alkanoic acid derivative, a frequently prescribed drug for the suppression of pain and inflammation, on the differentiation and proliferation of chondrocytes. AB - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed to relieve pain and inflammation. These NSAIDs have also analgesic effects and can be administered via oral, injectable, and topical routes. During inflammation, a number of synovial mediators and cytokines are released which decrease the pH level of the synovial fluid. Administration of acidic NSAIDs further decreases the pH levels and hence contributes to the destruction of the cartilage. To our knowledge, no cellular-based study regarding the chondrotoxicity of phenyl alkanoic acid derivatives on NSAIDs was conducted before. Thus, the aim of this pioneering study was to examine the effect of frequently prescribed NSAIDs, a phenyl alkanoic acid derivative, flurbiprofen, on the proliferation and differentiation of human primer chondrocyte cultures in vitro. METHODS: Primer chondrocyte cultures were prepared from osteochondral tissue obtained during surgery for gonarthrosis. Samples not exposed to the pharmacological agent were used as the control group. The samples were treated with 1, 10, 100, 250, 500, or 1000 MUM of the agent for 24, 48, and 72 h. The cell viability, toxicity, and proliferation were assessed with MTT (3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) analysis and prechondrocytic precursor stage-specific embryonic antigen-1 (SSEA-1) expression using a commercial ELISA kit spectrophotometrically. The surface morphology of the samples in each group was compared using an inverted light microscope and an environmental scanning electron microscope (ESEM). An analysis of variance was used to compare between-group differences. Tukey's honest significant difference (HSD) method (95 % confidence interval) was used to evaluate the differences and significance in averages. The alpha significance value was considered <0.01. RESULTS: Statistically significant cytotoxicity was observed in the treatment groups. NSAID had a significant negative effect on the proliferation and differentiation of chondrocytes as compared to the control group (p < 0.01). CONCLUSION: Before administering phenyl alkanoic acid derivatives in the clinical setting, their role in suppressing the proliferation and differentiation of chondrocytes should be taken into account. Thus, caution should be given when prescribing these drugs. PMID- 27363506 TI - Efficacy, safety, and tolerability of lacosamide in patients with gain-of function Nav1.7 mutation-related small fiber neuropathy: study protocol of a randomized controlled trial-the LENSS study. AB - BACKGROUND: Small fiber neuropathy generally leads to considerable pain and autonomic symptoms. Gain-of-function mutations in the SCN9A- gene, which codes for the Nav1.7 voltage-gated sodium channel, have been reported in small fiber neuropathy, suggesting an underlying genetic basis in a subset of patients. Currently available sodium channel blockers lack selectivity, leading to cardiac and central nervous system side effects. Lacosamide is an anticonvulsant, which blocks Nav1.3, Nav1.7, and Nav1.8, and stabilizes channels in the slow inactivation state. Since multiple Nav1.7 mutations in small fiber neuropathy showed impaired slow-inactivation, lacosamide might be effective. METHODS/DESIGN: The Lacosamide-Efficacy-'N'-Safety in Small fiber neuropathy (LENSS) study is a randomized, double-blind, placebo-controlled, crossover trial in patients with SCN9A-associated small fiber neuropathy, with the primary objective to evaluate the efficacy of lacosamide versus placebo. Eligible patients (the aim is to recruit 25) fulfilling the inclusion and exclusion criteria will be randomized to receive lacosamide (200 mg b.i.d.) or placebo during the first double-blinded treatment period (8 weeks), which is preceded by a titration period (3 weeks). The first treatment period will be followed by a tapering period (2 weeks). After a 2-week washout period, patients will crossover to the alternate arm for the second period consisting of an equal titration phase, treatment period, and tapering period. The primary efficacy endpoint will be the proportion of patients demonstrating a 1-point average pain score reduction compared to baseline using the Pain Intensity Numerical Rating Scale. We assume a response rate of approximately 60 % based on the criteria composed by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) group for measurement of pain. Patients withdrawing from the study will be considered non- responders. Secondary outcomes will include changes in maximum pain score, the Small Fiber Neuropathy Symptoms Inventory Questionnaire, sleep quality and the quality of life assessment, patients' global impressions of change, and safety and tolerability measurements. Sensitivity analyses will include assessing the proportion of patients having >= 2 points average pain improvement compared to the baseline Pain Intensity Numerical Rating Scale scores. DISCUSSION: This is the first study that will be evaluating the efficacy, safety, and tolerability of lacosamide versus placebo in patients with SCN9A-associated small fiber neuropathy. The findings may increase the knowledge on lacosamide as a potential treatment option in patients with painful neuropathies, considering the central role of Nav1.7 in pain. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01911975 . Registered on 13 July 2013. PMID- 27363507 TI - Synthesis of tertiary arylamines: Lewis acid-catalyzed direct reductive N alkylation of secondary amines with ketones through an alternative pathway. AB - We report herein a highly efficient, tin(ii)/PMHS catalyzed reductive N alkylation of arylamines with ketones affording tertiary arylamines. A very wide substrate scope was observed for the current catalytic method as all six permutations of ketones/aldehydes/heterocyclic carbonyls and primary/secondary/heterocyclic amines were well tolerated, enabling access to secondary, tertiary and heterocyclic amines. The method is also convenient for the synthesis of N-substituted isoindolinones and phthalazinones via a tandem amination-amidation sequence. Mechanistic investigations revealed a carbocationic pathway instead of an ordinary direct reductive amination pathway. PMID- 27363509 TI - A Diffusion Tensor Imaging Study in Children With ADHD, Autism Spectrum Disorder, OCD, and Matched Controls: Distinct and Non-Distinct White Matter Disruption and Dimensional Brain-Behavior Relationships. AB - OBJECTIVE: Neurodevelopmental disorders (NDDs) (attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) share genetic vulnerability and symptom domains. The authors present direct comparison of structural brain circuitry in children and adolescents with NDDs and control subjects and examine brain circuit-behavior relationships across NDDs using dimensional measures related to each disorder. METHOD: Diffusion imaging and behavioral measures were acquired in 200 children and adolescents (ADHD: N=31; OCD: N=36; ASD: N=71; controls: N=62; mean age range: 10.3-12.6 years). Following Tract-Based Spatial Statistics, multigroup comparison of white matter indices was conducted, followed by pairwise comparisons. Relationships of fractional anisotropy with dimensional measures of inattention, social deficits, obsessive-compulsive symptoms, and general adaptive functioning were conducted across the NDD sample. RESULTS: Lower fractional anisotropy within the splenium of the corpus callosum was found in each NDD group, compared with the control group. Lower fractional anisotropy in additional white matter tracts was found in the ASD and ADHD groups, compared with the control group, but not in the OCD group. Fractional anisotropy was lower in the ASD and ADHD groups compared with the OCD group but was not different in ADHD participants compared with ASD participants. A positive relation between fractional anisotropy (across much of the brain) and general adaptive functioning across NDDs was shown. CONCLUSIONS: This study identified disruption in interhemispheric circuitry (i.e., fractional anisotropy alterations in the corpus callosum) as a shared feature of ASD, ADHD, and OCD. However, fractional anisotropy alterations may be more widespread and severe in ASD and ADHD than in OCD. Higher fractional anisotropy throughout the brain appears to be related to better adaptive function across NDDs. PMID- 27363508 TI - An Individualized Risk Calculator for Research in Prodromal Psychosis. AB - OBJECTIVE: Approximately 20%-35% of individuals 12-35 years old who meet criteria for a prodromal risk syndrome convert to psychosis within 2 years. However, this estimate ignores the fact that clinical high-risk cases vary considerably in risk. The authors sought to create a risk calculator, based on profiles of risk indicators, that can ascertain the probability of conversion to psychosis in individual patients. METHOD: The study subjects were 596 clinical high-risk participants from the second phase of the North American Prodrome Longitudinal Study who were followed up to the time of conversion to psychosis or last contact (up to 2 years). The predictors examined were limited to those that are supported by previous studies and are readily obtainable in general clinical settings. Time to-event regression was used to build a multivariate model predicting conversion, with internal validation using 1,000 bootstrap resamples. RESULTS: The 2-year probability of conversion to psychosis was 16%. Higher levels of unusual thought content and suspiciousness, greater decline in social functioning, lower verbal learning and memory performance, slower speed of processing, and younger age at baseline each contributed to individual risk for psychosis. Stressful life events, trauma, and family history of schizophrenia were not significant predictors. The multivariate model achieved a concordance index of 0.71 and, as reported in an article by Carrion et al., published concurrently with this one, was validated in an independent external data set. The results are instantiated in a web-based risk prediction tool envisioned to be most useful in research protocols involving the psychosis prodrome. CONCLUSIONS: A risk calculator comparable in accuracy to those for cardiovascular disease and cancer is available to predict individualized conversion risks in newly ascertained clinical high-risk cases. Given that the risk calculator can be validly applied only for patients who screen positive on the Structured Clinical Interview for Psychosis Risk Syndromes, which requires training to administer, its most immediate uses will be in research on psychosis risk factors and in research driven clinical (prevention) trials. PMID- 27363510 TI - Blunted Neural Response to Rewards as a Prospective Predictor of the Development of Depression in Adolescent Girls. AB - OBJECTIVE: A blunted neural response to rewards has recently emerged as a potential mechanistic biomarker of adolescent depression. The reward positivity, an event-related potential elicited by feedback indicating monetary gain relative to loss, has been associated with risk for depression. The authors examined whether the reward positivity prospectively predicted the development of depression 18 months later in a large community sample of adolescent girls. METHOD: The sample included 444 girls 13.5-15.5 years old with no lifetime history of a depressive disorder, along with a biological parent for each girl. At baseline, the adolescents' reward positivity was measured using a monetary guessing task, their current depressive symptoms were assessed using a self report questionnaire, and the adolescents' and parents' lifetime psychiatric histories were evaluated with diagnostic interviews. The same interview and questionnaire were administered to the adolescents again approximately 18 months later. RESULTS: A blunted reward positivity at baseline predicted first-onset depressive disorder and greater depressive symptom scores 18 months later. The reward positivity was also a significant predictor independent of other prominent risk factors, including baseline depressive symptoms and adolescent and parental lifetime psychiatric history. The combination of a blunted reward positivity and greater depressive symptom scores at baseline provided the greatest positive predictive value for first-onset depressive disorder. CONCLUSIONS: This study provides strong converging evidence that a blunted neural response to rewards precedes adolescent-onset depression and symptom emergence. Blunted neural response may therefore constitute an important target for screening and prevention. PMID- 27363512 TI - Effects of metal-bearing nanoparticles (Ag, Au, CdS, ZnO, SiO2) on developing zebrafish embryos. AB - Due to the increasing commercialization of consumer and industrial products containing nanoparticles (NPs), an increase in the introduction of these materials into the environment is expected. NP toxicity to aquatic organisms depends on multiple biotic and abiotic factors, resulting in an unlimited number of combinations impossible to test in practice. The zebrafish embryo model offers a useful screening tool to test and rank the toxicity of nanomaterials according to those diverse factors. This work aims to study the acute and sublethal toxicity of a set of metal-bearing NPs displaying different properties, in comparison to that of the ionic and bulk forms of the metals, in order to establish a toxicity ranking. Soluble NPs (Ag, CdS and ZnO) showed the highest acute and sublethal toxicity, with LC50 values as low as 0.529 mg Ag l(-1) for Ag NPs of 20 nm, and a significant increase in the malformation prevalence in embryos exposed to 0.1 mg Cd l(-1) of CdS NPs of ~4 nm. For insoluble NPs, like SiO2 NPs, acute effects were not observed during early embryo development due to the protective effect of the chorion. But effects on larvae could be expected, since deposition of fluorescent SiO2 NPs over the gill lamella and excretion through the intestine were observed after hatching. In other cases, such as for gold NPs, the toxicity could be attributed to the presence of additives (sodium citrate) in the NP suspension, as they displayed a similar toxicity when tested separately. Overall, the results indicated that toxicity to zebrafish embryos depends primarily on the chemical composition and, thus, the solubility of the NPs. Other characteristics, such as size, played a secondary role. This was supported by the observation that ionic forms of the metals were always more toxic than the nano forms, and bulk forms were the least toxic to the developing zebrafish embryos. PMID- 27363511 TI - Personalized Prediction of Psychosis: External Validation of the NAPLS-2 Psychosis Risk Calculator With the EDIPPP Project. AB - OBJECTIVE: As part of the second phase of the North American Prodrome Longitudinal Study (NAPLS-2), Cannon and colleagues report, concurrently with the present article, on a risk calculator for the individualized prediction of a psychotic disorder in a 2-year period. The present study represents an external validation of the NAPLS-2 psychosis risk calculator using an independent sample of patients at clinical high risk for psychosis collected as part of the Early Detection, Intervention, and Prevention of Psychosis Program (EDIPPP). METHOD: Of the total EDIPPP sample of 210 subjects rated as being at clinical high risk based on the Structured Interview for Prodromal Syndromes, 176 had at least one follow-up assessment and were included in the construction of a new prediction model with six predictor variables in the NAPLS-2 psychosis risk calculator (unusual thoughts and suspiciousness, symbol coding test performance, verbal learning test performance, decline in social functioning, baseline age, and family history). Discrimination performance was assessed with the area under the receiver operating characteristic curve (AUC). The NAPLS-2 risk calculator was then used to generate a psychosis risk estimate for each case in the external validation sample. RESULTS: The external validation model showed good discrimination, with an AUC of 0.790 (95% CI=0.644-0.937). In addition, the personalized risk generated by the risk calculator provided a solid estimation of the actual conversion outcome in the validation sample. CONCLUSIONS: Two independent samples of clinical high-risk patients converge to validate the NAPLS 2 psychosis risk calculator. This prediction calculator represents a meaningful step toward early intervention and the personalized treatment of psychotic disorders. PMID- 27363514 TI - BODIPY catalyzed amide synthesis promoted by BHT and air under visible light. AB - A novel and efficient protocol for the synthesis of amides is reported which employs a BODIPY catalyzed oxidative amidation reaction between aromatic aldehydes and amines under visible light. Compared with the known Ru or Ir molecular catalysts and other organic dyes, the BODIPY catalyst showed higher reactivity toward this reaction. Mechanistic studies reveal that dioxygen could be activated through an ET and a SET pathway, forming active peroxides in situ, which are vital for the key step of the reaction, i.e. the oxidation of hemiaminal to amide. The broad substrate scope and mild reaction conditions make this reaction practically useful and environmentally friendly for the synthesis of amide compounds. PMID- 27363513 TI - Specificity and mechanism of action of alpha-helical membrane-active peptides interacting with model and biological membranes by single-molecule force spectroscopy. AB - In this study, to systematically investigate the targeting specificity of membrane-active peptides on different types of cell membranes, we evaluated the effects of peptides on different large unilamellar vesicles mimicking prokaryotic, normal eukaryotic, and cancer cell membranes by single-molecule force spectroscopy and spectrum technology. We revealed that cationic membrane active peptides can exclusively target negatively charged prokaryotic and cancer cell model membranes rather than normal eukaryotic cell model membranes. Using Acholeplasma laidlawii, 3T3-L1, and HeLa cells to represent prokaryotic cells, normal eukaryotic cells, and cancer cells in atomic force microscopy experiments, respectively, we further studied that the single-molecule targeting interaction between peptides and biological membranes. Antimicrobial and anticancer activities of peptides exhibited strong correlations with the interaction probability determined by single-molecule force spectroscopy, which illustrates strong correlations of peptide biological activities and peptide hydrophobicity and charge. Peptide specificity significantly depends on the lipid compositions of different cell membranes, which validates the de novo design of peptide therapeutics against bacteria and cancers. PMID- 27363515 TI - Synthesis and catalytic applications of 1,2,3-triazolylidene gold(i) complexes in silver-free oxazoline syntheses and C-H bond activation. AB - A series of novel 1,2,3-triazolylidene gold(i) chloride complexes have been synthesised and fully characterised. Silver-free methodologies for chloride ion abstraction of these complexes were evaluated for their potential as Au-based catalyst precursors. Using simple potassium salts or MeOTf as chloride scavengers produced metal complexes that catalyse both the regioselective synthesis of oxazolines and the C-H activation of benzene or styrene for carbene transfer from ethyl diazoacetate. These results indicate that Ag-free activation of 1,2,3 triazolylidene gold(i) chloride complexes is feasible for the generation of catalytically active Au triazolylidene species. However, silver-mediated activation imparts substantially higher catalytic activity in oxazoline synthesis. PMID- 27363516 TI - The metabolome of [2-(14)C](-)-epicatechin in humans: implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives. AB - Diet is a major life style factor affecting human health, thus emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of essential nutrients and minerals. This limited understanding can be attributed to some extent to a lack of fundamental data describing the absorption, distribution, metabolism and excretion (ADME) of bioactive compounds. Consequently, we selected the flavanol (-)-epicatechin (EC) as an example of a widely studied bioactive food constituent and investigated the ADME of [2-(14)C](-)-epicatechin (300 MUCi, 60 mg) in humans (n = 8). We demonstrated that 82 +/- 5% of ingested EC was absorbed. We also established pharmacokinetic profiles and identified and quantified >20 different metabolites. The gut microbiome proved to be a key driver of EC metabolism. Furthermore, we noted striking species-dependent differences in the metabolism of EC, an insight with significant consequences for investigating the mechanisms of action underlying the beneficial effects of EC. These differences need to be considered when assessing the safety of EC intake in humans. We also identified a potential biomarker for the objective assessment of EC intake that could help to strengthen epidemiological investigations. PMID- 27363517 TI - Accelerating skin wound healing by M-CSF through generating SSEA-1 and -3 stem cells in the injured sites. AB - Wound healing is a complicated process requiring the collaborative efforts of different cell lineages. Our recent studies have found that one subset of hematopoietic cells can be induced to dedifferentiate into multipotent stem cells by means of a proliferating fibroblast releasable factor, M-CSF. Understanding the importance of stem cells on skin wound healing, here we evaluate the biological significance of M-CSF on skin wound healing. In an in vivo mouse skin excisional wound model, we found that SSEA-positive stem cells were present in wounded but not normal skin. After isolating skin cells from either normal or wounded skin by collagenase digestion, and analyzing the SSEA-1 positive cells by flow cytometry, we found a significant increase in the number of SSEA-1 positive cells in wounded skin. Topical application of M-CSF in skin wounds accelerated healing remarkably, while application of M-CSF-neutralizing antibody slowed wound healing. Furthermore, injection of EGFP-labeled hematopoietic cell-derived stem cells generated from M-CSF treated splenocytes resulted in EGFP-labeled cells being enriched in the skin wound site and further differentiated into functional organ-specific cells. Together, these data demonstrated that M-CSF makes a significant contribution to the healing process by inducing hematopoietic cell dedifferentiation into stem cells. PMID- 27363518 TI - High intake of fatty fish, but not of lean fish, affects serum concentrations of TAG and HDL-cholesterol in healthy, normal-weight adults: a randomised trial. AB - The aim of the present study was to examine whether high intake of lean or fatty fish (cod and farmed salmon, respectively) by healthy, normal-weight adults would affect risk factors of type 2 diabetes and CVD when compared with lean meat (chicken). More knowledge is needed concerning the potential health effects of high fish intake (>300 g/week) in normal-weight adults. In this randomised clinical trial, thirty-eight young, healthy, normal-weight participants consumed 750 g/week of lean or fatty fish or lean meat (as control) for 4 weeks at dinner according to provided recipes to ensure similar ways of preparations and choices of side dishes between the groups. Energy and macronutrient intakes at baseline and end point were similar in all groups, and there were no changes in energy and macronutrient intakes within any of the groups during the course of the study. High intake of fatty fish, but not lean fish, significantly reduced TAG and increased HDL-cholesterol concentrations in fasting serum when compared with lean meat intake. When compared with lean fish intake, fatty fish intake increased serum HDL-cholesterol. No differences were observed between lean fish, fatty fish and lean meat groups regarding fasting and postprandial glucose regulation. These findings suggest that high intake of fatty fish, but not of lean fish, could beneficially affect serum concentrations of TAG and HDL-cholesterol, which are CVD risk factors, in healthy, normal-weight adults, when compared with high intake of lean meat. PMID- 27363519 TI - Evaluation Methods for Assessing Users' Psychological Experiences of Web-Based Psychosocial Interventions: A Systematic Review. AB - BACKGROUND: The use of Web-based interventions to deliver mental health and behavior change programs is increasingly popular. They are cost-effective, accessible, and generally effective. Often these interventions concern psychologically sensitive and challenging issues, such as depression or anxiety. The process by which a person receives and experiences therapy is important to understanding therapeutic process and outcomes. While the experience of the patient or client in traditional face-to-face therapy has been evaluated in a number of ways, there appeared to be a gap in the evaluation of patient experiences of therapeutic interventions delivered online. Evaluation of Web based artifacts has focused either on evaluation of experience from a computer Web-design perspective through usability testing or on evaluation of treatment effectiveness. Neither of these methods focuses on the psychological experience of the person while engaged in the therapeutic process. OBJECTIVE: This study aimed to investigate what methods, if any, have been used to evaluate the in situ psychological experience of users of Web-based self-help psychosocial interventions. METHODS: A systematic literature review was undertaken of interdisciplinary databases with a focus on health and computer sciences. Studies that met a predetermined search protocol were included. RESULTS: Among 21 studies identified that examined psychological experience of the user, only 1 study collected user experience in situ. The most common method of understanding users' experience was through semistructured interviews conducted posttreatment or questionnaires administrated at the end of an intervention session. The questionnaires were usually based on standardized tools used to assess user experience with traditional face-to-face treatment. CONCLUSIONS: There is a lack of methods specified in the literature to evaluate the interface between Web based mental health or behavior change artifacts and users. Main limitations in the research were the nascency of the topic and cross-disciplinary nature of the field. There is a need to develop and deliver methods of understanding users' psychological experiences while using an intervention. PMID- 27363520 TI - Inhibition of HIV-1 reactivation by a telomerase-derived peptide in a HSP90 dependent manner. AB - A peptide vaccine designed to induce T-cell immunity to telomerase, GV1001, has been shown to modulate cellular signaling pathways and confer a direct anti cancer effect through the interaction with heat shock protein (HSP) 90 and 70. Here, we have found that GV1001 can modulate transactivation protein-mediated human immunodeficiency virus (HIV)-1 transactivation in an HSP90-dependent manner. GV1001 treatment resulted in significant suppression of HIV-1 replication and rescue of infected cells from death by HIV-1. Transactivation of HIV-long terminal repeat (LTR) was inhibited by GV1001, indicating that GV1001 suppressed the transcription from proviral HIV DNA. The anti-HIV-1 activity of GV1001 was completely abrogated by an HSP90-neutralizing antibody, indicating that the antiviral activity depends on HSP90. Further mechanistic studies revealed that GV1001 suppresses basal NF-kappaB activation, which is required for HIV-1 LTR transactivation in an HSP90-dependent manner. Inhibition of LTR transactivation by GV1001 suggests its potential to suppress HIV-1 reactivation from latency. Indeed, PMA-mediated reactivation of HIV-1 from latent infected cells was suppressed by GV1001. The results suggest the potential therapeutic use of GV1001, a peptide proven to be safe for human use, as an anti-HIV-1 agent to suppress the reactivation from latently infected cells. PMID- 27363522 TI - 'Squeezing' near-field thermal emission for ultra-efficient high-power thermophotovoltaic conversion. AB - We numerically demonstrate near-field planar ThermoPhotoVoltaic systems with very high efficiency and output power, at large vacuum gaps. Example performances include: at 1200 degrees K emitter temperature, output power density 2 W/cm(2) with ~47% efficiency at 300 nm vacuum gap; at 2100 degrees K, 24 W/cm(2) with ~57% efficiency at 200 nm gap; and, at 3000 degrees K, 115 W/cm(2) with ~61% efficiency at 140 nm gap. Key to this striking performance is a novel photonic design forcing the emitter and cell single modes to cros resonantly couple and impedance-match just above the semiconductor bandgap, creating there a 'squeezed' narrowband near-field emission spectrum. Specifically, we employ surface-plasmon polariton thermal emitters and silver-backed semiconductor-thin-film photovoltaic cells. The emitter planar plasmonic nature allows for high-power and stable high temperature operation. Our simulations include modeling of free-carrier absorption in both cell electrodes and temperature dependence of the emitter properties. At high temperatures, the efficiency enhancement via resonant mode cross-coupling and matching can be extended to even higher power, by appropriately patterning the silver back electrode to enforce also an absorber effective surface-plasmon-polariton mode. Our proposed designs can therefore lead the way for mass-producible and low-cost ThermoPhotoVoltaic micro-generators and solar cells. PMID- 27363521 TI - Still and rotating myosin clusters determine cytokinetic ring constriction. AB - The cytokinetic ring is essential for separating daughter cells during division. It consists of actin filaments and myosin motors that are generally assumed to organize as sarcomeres similar to skeletal muscles. However, direct evidence is lacking. Here we show that the internal organization and dynamics of rings are different from sarcomeres and distinct in different cell types. Using micro cavities to orient rings in single focal planes, we find in mammalian cells a transition from a homogeneous distribution to a periodic pattern of myosin clusters at the onset of constriction. In contrast, in fission yeast, myosin clusters rotate prior to and during constriction. Theoretical analysis indicates that both patterns result from acto-myosin self-organization and reveals differences in the respective stresses. These findings suggest distinct functional roles for rings: contraction in mammalian cells and transport in fission yeast. Thus self-organization under different conditions may be a generic feature for regulating morphogenesis in vivo. PMID- 27363523 TI - Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease. AB - Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. Activation of macrophages and hepatic stellate cells is a critical step that promotes liver fibrosis. We aimed to explore the feasibility of interleukin-34 (IL-34), a key regulator of macrophages, as a fibrosis marker in patients with NAFLD. We enrolled 197 liver biopsy-proven NAFLD patients. We evaluated the serum levels of IL-34, macrophage-colony stimulating factor (M CSF), soluble CD163 (sCD163), 40 cytokines/chemokines, hyaluronic acid, type IV collagen 7s, and clinically-approved fibrosis scores. IL-34 increased with the progression of fibrosis and was an independent marker for liver fibrosis. Immunostaining experiments, using resected liver specimens from NAFLD patients, revealed that IL-34 was mainly expressed on liver fibroblasts. IL-34 based fibrosis score (0.0387*IL-34 (pg/ml) + 0.3623*type IV collagen 7s (ng/ml) + 0.0184*age (year)-1.1850) was a practical predictive model of liver fibrosis. Using receiver-operating characteristic analyses, the area under the curve, sensitivity, and specificity of IL-34 based fibrosis score were superior or comparable to the other fibrosis biomarkers and scores. In conclusion, the IL-34 based fibrosis score, including serum IL-34, type IV collagen 7s and age, is a feasible diagnostic marker of liver fibrosis in NAFLD patients. PMID- 27363524 TI - Prevalence of Entamoeba histolytica, Giardia lamblia, and Cryptosporidium spp. in Libya: 2000-2015. AB - INTRODUCTION: The intestinal protozoa Entamoeba histolytica, Giardia lamblia, and Cryptosporidium spp. are the causative agents of giardiasis, amebiasis, and cryptosporidiosis, respectively. Adequate knowledge of the geographical distribution of parasites and the demographic variables that influence their prevalence is important for effective control of infection in at-risk populations. METHODS: The data were obtained by an English language literature search of Medline and PubMed for papers using the search terms 'intestinal parasites and Libya, G. lamblia and Libya, E. histolytica and Libya and Cryptosporidium and Libya' for the period 2000-2015. RESULTS: The data obtained for the period 2000-2015 showed prevalence rates of 0.8-36.6% (mean 19.9%) for E. histolytica/dispar, 1.2-18.2% (mean 4.6%) for G. lamblia and 0.9-13% (mean 3.4%) for Cryptosporidium spp. among individuals in Libya with gastroenteritis (GE). On the other hand, prevalence rates of 0.8-16.3% (mean 8.3%), 1.8-28.8% (mean 4.8%), and 1.0-2.5% (mean=2.4), respectively, were observed for individuals without GE. The mean prevalence rate of E. histolytica/dispar was significantly higher among individuals with GE compared with those without GE (p<0.0000001, OR=2.74). No significant difference in prevalence rate of the three organisms was found according to gender, but most of infections were observed in children aged 10 years or younger. CONCLUSION: The reviewed data suggest that E. histolytica, G. lamblia, and Cryptosporidium spp. may play a minor role in GE in Libya. The observed high prevalence rates of E. histolytica/dispar reported from Libya could be due mainly to the non-pathogenic E. dispar and E. moshkovskii. However, more studies are needed in the future using E. histolytica-specific enzyme immunoassays and/or molecular methods to confirm this observation. PMID- 27363526 TI - Novel class of collector in electrospinning device for the fabrication of 3D nanofibrous structure for large defect load-bearing tissue engineering application. AB - Adequate porosity, appropriate pore size, and 3D-thick shape are crucial parameters in the design of scaffolds, as they should provide the right space for cell adhesion, spreading, migration, and growth. In this work, a novel design for fabricating a 3D nanostructured scaffold by electrospinning was taken into account. Helical spring-shaped collector was purposely designed and used for electrospinning PCL fibers. Improved morphological properties and more uniform diameter distribution of collected nanofibers on the turns of helical spring shaped collector are confirmed by SEM analysis. SEM images elaboration showed 3D pores with average diameter of 4 and 5.5 micrometer in x-y plane and z-direction, respectively. Prepared 3D scaffold possessed 99.98% porosity which led to the increased water uptake behavior in PBS at 37 degrees C up to 10 days, and higher degradation rate compared to 2D flat structure. Uniaxial compression test on 3D scaffolds revealed an elastic modulus of 7 MPa and a stiffness of 102 MPa, together with very low hysteresis area and residual strain. In vitro cytocompatibility test with MG-63 osteoblast-like cells using AlamarBlueTM colorimetric assay, indicated a continuous increase in cell viability for the 3D structure over the test duration. SEM observation showed enhanced cells spreading and diffusion into the underneath layers for 3D scaffold. Accelerated calcium deposition in 3D substrate was confirmed by EDX analysis. Obtained morphological, physical, and mechanical properties together with in vitro cytocompatibility results, suggest this novel technique as a proper method for the fabrication of 3D nanofibrous scaffolds for the regeneration of critical-size load bearing defects. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1535 1548, 2017. PMID- 27363525 TI - Deciphering the recent phylogenetic expansion of the originally deeply rooted Mycobacterium tuberculosis lineage 7. AB - BACKGROUND: A deeply rooted phylogenetic lineage of Mycobacterium tuberculosis (M. tuberculosis) termed lineage 7 was discovered in Ethiopia. Whole genome sequencing of 30 lineage 7 strains from patients in Ethiopia was performed. Intra lineage genome variation was defined and unique characteristics identified with a focus on genes involved in DNA repair, recombination and replication (3R genes). RESULTS: More than 800 mutations specific to M. tuberculosis lineage 7 strains were identified. The proportion of non-synonymous single nucleotide polymorphisms (nsSNPs) in 3R genes was higher after the recent expansion of M. tuberculosis lineage 7 strain started. The proportion of nsSNPs in genes involved in inorganic ion transport and metabolism was significantly higher before the expansion began. A total of 22346 bp deletions were observed. Lineage 7 strains also exhibited a high number of mutations in genes involved in carbohydrate transport and metabolism, transcription, energy production and conversion. CONCLUSIONS: We have identified unique genomic signatures of the lineage 7 strains. The high frequency of nsSNP in 3R genes after the phylogenetic expansion may have contributed to recent variability and adaptation. The abundance of mutations in genes involved in inorganic ion transport and metabolism before the expansion period may indicate an adaptive response of lineage 7 strains to enable survival, potentially under environmental stress exposure. As lineage 7 strains originally were phylogenetically deeply rooted, this may indicate fundamental adaptive genomic pathways affecting the fitness of M. tuberculosis as a species. PMID- 27363527 TI - Hierarchical polymer coating for optimizing the antifouling and bactericidal efficacies. AB - The bacteria-repellent and bactericidal functionalities in a single system are generally need to be carefully optimized in order to obtain the highest antibacterial performance. In this study, the controlled SI-PIMP strategy was developed for creating hierarchical polymer brushes possessing the bacteria repellent and bactericidal functionalities. To obtain a bactericidal surface with minimal interference to its nonfouling property, optimization studies were conducted by facilely tailoring the surface density of the quaternary ammonium compound moieties through control over the monomer concentration. An optimal hierarchical polymer coating showed potent protein and bacteria repellence as well as certain bactericidal property. The longlasting antibacterial performance was also achieved due to the good balance between the dual functionalities. The tenability of the hierarchical polymer coating is applicable to surface chemistries for biosensors, molecular imaging, and biomedical applications. PMID- 27363528 TI - Liver stiffness measurement using acoustic radiation force impulse elastography in overweight and obese patients. AB - BACKGROUND: Obesity and overweight are global health problems. AIM: To evaluate the diagnostic accuracy of liver stiffness measurement (LSM) using acoustic radiation force impulse (ARFI) elastography in overweight and obese patients for staging liver fibrosis. METHODS: Ninety-seven patients (mean age: 50 years, 50% male) with body mass index (BMI) >=25 kg/m(2) (mean BMI: 31 kg/m(2) ) were prospectively enrolled. All patients underwent ARFI elastography and liver biopsy. In 87/97 patients, transient elastography (TE) was performed (M- and XL probes). Patients were divided into two groups respectively: overweight: BMI <30 kg/m(2) (n = 61); and obese: BMI >=30 kg/m(2) (n = 26). RESULTS: Acoustic radiation force impulse elastography correlated with liver fibrosis in overweight (r = 0.84, P < 0.0001) and obese patients (r = 0.85, P < 0.0001), while no correlation was observed with steatosis, steatohepatitis and BMI. Area under the curve detecting liver cirrhosis for ARFI and TE were 0.97 in overweight and 0.94 and 0.92 in obese patients. In both groups, the failure rate was lower for ARFI than TE. ARFI of liver segment 8 showed a lower discordance than TE in both groups (overweight: 3% vs. 12%, P = 0.002; obese: 8% vs. 27%, P = 0.034). Steatosis and steatohepatitis were neither predictors of discordance nor of performance in LSM by ARFI or TE in both groups. CONCLUSIONS: In overweight and obese patients, acoustic radiation force impulse can diagnose liver cirrhosis and significant fibrosis with high diagnostic accuracy. Liver stiffness measurement using the XL-probe reduces the influence of BMI, steatosis and steatohepatitis. The failure and discordance rates were lower for acoustic radiation force impulse than transient elastography in both patients groups. PMID- 27363529 TI - Right ventricular outflow tract obstruction in complicated monochorionic twin pregnancy. AB - OBJECTIVES: Severe right ventricular outflow tract obstruction (RVOTO) is a potential complication in recipient twins of twin-to-twin transfusion syndrome (TTTS) that requires postnatal follow-up or treatment. We aimed to evaluate pregnancy characteristics of neonates with RVOTO from complicated monochorionic twin pregnancies, determine the incidence of RVOTO in TTTS cases and construct a prediction model for its development. METHODS: This was an observational cohort study of all complicated monochorionic twin pregnancies with a postnatal diagnosis of RVOTO examined at our center. Cases were referred for evaluation of the need for fetal therapy or intervention because of TTTS, selective intrauterine growth restriction (sIUGR) or multiple congenital malformations in one of the twins. Ultrasound data were retrieved from our monochorionic twin database. Among liveborn TTTS recipients treated prenatally with laser therapy, those with RVOTO were compared with those without RVOTO (controls). We describe four additional cases with RVOTO that were not TTTS recipients. RESULTS: A total of 485 twin pregnancies received laser therapy for TTTS during the study period. RVOTO was diagnosed in 3% (11/368) of liveborn TTTS recipients, of whom two showed mild Ebstein's anomaly. Before laser therapy, pericardial effusion was seen in 45% (5/11) of RVOTO cases (P < 0.01) and abnormal A-wave in the ductus venosus (DV) in 73% (8/11) (P = 0.03), significantly higher proportions than in controls. Mean gestational age at laser therapy was 17 + 3 weeks in RVOTO cases compared with 20 + 3 weeks in controls (P = 0.03). A prediction model for RVOTO was constructed incorporating these three significant variables. One TTTS donor had RVOTO after the development of transient hydrops following laser therapy. Three larger twins in pregnancies complicated by sIUGR developed RVOTO, the onset of which was detectable early in the second trimester. CONCLUSIONS: RVOTO occurs in TTTS recipient twins but can also develop in TTTS donors and larger twins of pregnancies complicated by sIUGR. Abnormal flow in the DV, pericardial effusion and early gestational age at onset of TTTS are predictors of RVOTO in TTTS recipients, which suggests increased vulnerability to hemodynamic imbalances in the fetal heart in early pregnancy. These findings could guide diagnostic follow up protocols after TTTS treatment. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27363530 TI - Synthesis and Photoisomerization of Substituted Dibenzofulvene Molecular Rotors. AB - The synthesis, spectral and structural characterization, and photoisomerization of a family of 2-substituted dibenzofulvene molecular actuators based on (2,2,2 triphenylethylidene)fluorene (TEF) are reported. The 2-substituted species investigated are nitro (NTEF), cyano (CTEF), and iodo (ITEF). X-ray structures of these three compounds and three intermediates were determined to assign alkene configuration and investigate the effects of the 2-substituents on steric gearing. The addition-elimination reaction of Z-9 with trityl anion to form Z-10 proceeded with complete retention of configuration. Rates of photoisomerization were measured at irradiation wavelengths between 266-355 nm in acetonitrile/dioxane solutions at room temperature. Photoisomerization quantum yields (phi) were calculated by means of a mathematical model that accounts for a certain degree of photodecomposition in the cases of CTEF and ITEF. Quantum yields vary significantly with substituent, having maximum values of phi=0.26 for NTEF, 0.39 for CTEF, and 0.50 for ITEF. NTEF is photochemically robust and has a large quantum yield for photoisomerization in the near-UV, making it a particularly promising drive rotor moiety for light-powered molecular devices. PMID- 27363531 TI - THE EFFECTS OF FOOD INTAKE AND ITS FAT COMPOSITION ON INTESTINAL ECHOGENICITY IN HEALTHY DOGS. AB - Dogs presenting for ultrasonography due to suspected gastrointestinal disease might have residual ingesta and this could have an affect on the appearance of intestinal mucosa unrelated to pathology. The purpose of this prospective descriptive study was to determine effects of a recent meal consisting of the recommended daily fat content (meal 1) and a higher fat one (meal 2) on mucosal echogenicity in healthy dogs. Sixty client-owned and clinically healthy dogs were recruited. Two meals, one with 15% fat dry matter basis (meal 1) and a second with 1.5 ml/kg body weight corn oil added to result in a range of 41-63% fat dry matter basis (meal 2), were fed 1 week apart after a 12 h fast. Mucosal echogenicity scores were assigned at fasting, immediate postprandial and at 60 min after each meal. Duodenal scores were significantly greater for meal 1 at 60 min (P < 0.001) as opposed to fasting and immediate postprandial. With meal 2, the duodenal score was significantly different (P < 0.001) at the immediate and 60-min data point compared to meal 1. Jejunal scores were significantly greater for meal 1 at the 60-min data point (P < 0.001) as opposed to fasting and immediate postprandial. With meal 2, the jejunal score was significantly different (P < 0.001) only at the 60-min data point compared to meal 1. Intestinal mucosal echogenicity can be increased in healthy dogs after food intake, regardless of fat content. This effect should be taken into consideration when increased mucosal echogenicity is identified in clinical patients. PMID- 27363532 TI - CO2 Activation and Hydrogenation by PtHn (-) Cluster Anions. AB - Gas phase reactions between PtHn (-) cluster anions and CO2 were investigated by mass spectrometry, anion photoelectron spectroscopy, and computations. Two major products, PtCO2 H(-) and PtCO2 H3 (-) , were observed. The atomic connectivity in PtCO2 H(-) can be depicted as HPtCO2 (-) , where the platinum atom is bonded to a bent CO2 moiety on one side and a hydrogen atom on the other. The atomic connectivity of PtCO2 H3 (-) can be described as H2 Pt(HCO2 )(-) , where the platinum atom is bound to a formate moiety on one side and two hydrogen atoms on the other. Computational studies of the reaction pathway revealed that the hydrogenation of CO2 by PtH3 (-) is highly energetically favorable. PMID- 27363533 TI - Molecular characterization of glycation-associated skin ageing: an alternative skin model to study in vitro antiglycation activity of topical cosmeceutical and pharmaceutical formulations. AB - BACKGROUND: Glycation is a nonenzymatic reaction that cross-links a sugar molecule and protein macromolecule to form advanced glycation products (AGEs) that are associated with various age-related disorders; thus glycation plays an important role in skin chronological ageing. OBJECTIVES: To develop a novel in vitro skin glycation model as a screening tool for topical formulations with antiglycation properties and to further characterize, at the molecular level, the glycation stress-driven skin ageing mechanism. METHODS: The glycation model was developed using human reconstituted full-thickness skin; the presence of Nepsilon -(carboxymethyl) lysine (CML) was used as evidence of the degree of glycation. Topical application of emulsion containing a well-known antiglycation compound (aminoguanidine) was used to verify the sensitivity and robustness of the model. Cytokine immunoassay, quantitative real-time polymerase chain reaction and histological analysis were further implemented to characterize the molecular mechanisms of skin ageing in the skin glycation model. RESULTS: Transcriptomic and cytokine profiling analyses in the skin glycation model demonstrated multiple biological changes, including extracellular matrix catabolism, skin barrier function impairment, oxidative stress and subsequently the inflammatory response. Darkness and yellowness of skin tone observed in the in vitro skin glycation model correlated well with the degree of glycation stress. CONCLUSIONS: The newly developed skin glycation model in this study has provided a new technological dimension in screening antiglycation properties of topical pharmaceutical or cosmeceutical formulations. This study concomitantly provides insights into skin ageing mechanisms driven by glycation stress, which could be useful in formulating skin antiageing therapy in future studies. PMID- 27363534 TI - Fast and accurate dynamic estimation of field effectiveness of meningococcal vaccines. AB - BACKGROUND: Estimating the effectiveness of meningococcal vaccines with high accuracy and precision can be challenging due to the low incidence of the invasive disease, which ranges between 0.5 and 1 cases per 100,000 in Europe and North America. Vaccine effectiveness (VE) is usually estimated with a screening method that combines in one formula the proportion of meningococcal disease cases that have been vaccinated and the proportion of vaccinated in the overall population. Due to the small number of cases, initial point estimates are affected by large uncertainties and several years may be required to estimate VE with a small confidence interval. METHODS: We used a Monte Carlo maximum likelihood (MCML) approach to estimate the effectiveness of meningococcal vaccines, based on stochastic simulations of a dynamic model for meningococcal transmission and vaccination. We calibrated the model to describe two immunization campaigns: the campaign against MenC in England and the Bexsero campaign that started in the UK in September 2015. First, the MCML method provided estimates for both the direct and indirect effects of the MenC vaccine that were validated against results published in the literature. Then, we assessed the performance of the MCML method in terms of time gain with respect to the screening method under different assumptions of VE for Bexsero. RESULTS: MCML estimates of VE for the MenC immunization campaign are in good agreement with results based on the screening method and carriage studies, yet characterized by smaller confidence intervals and obtained using only incidence data collected within 2 years of scheduled vaccination. Also, we show that the MCML method could provide a fast and accurate estimate of the effectiveness of Bexsero, with a time gain, with respect to the screening method, that could range from 2 to 15 years, depending on the value of VE measured from field data. CONCLUSIONS: Results indicate that inference methods based on dynamic computational models can be successfully used to quantify in near real time the effectiveness of immunization campaigns against Neisseria meningitidis. Such an approach could represent an important tool to complement and support traditional observational studies, in the initial phase of a campaign. PMID- 27363535 TI - Photodynamic therapy versus surgical excision to basal cell carcinoma: meta analysis. AB - BACKGROUND: Surgical excision (SE) is a first-line treatment for basal cell carcinoma (BCC). Topical photodynamic therapy (PDT) has also been used and has cosmetic advantages over surgery. The latest European guidelines for topical PDT recommended that it be used to treat nodular basal cell carcinoma (nBCC) but a consensus has not been reached. Our study was to evaluate the efficacy of PDT versus SE for the treatment for nBCC by a meta-analysis. MATERIALS AND METHODS: We searched PubMed, EMBASE, the Cochrane Library, CKNI, VIP, and relevant references up to October 2014 including randomized controlled trials (RCTs) that compared PDT with SE for treatment of nBCC patients. A meta-analysis was conducted by using the Cochrane Collaboration's revman 5.0 software. RESULTS: We selected five studies that covered 596 of pathologically confirmed nBCC. We compared complete response rate (RR) of PDT and SE at 3 months and 1, 2, 3, 4, and 5 years. We found that the RR was 0.95 (0.90, 1.00), 0.89 (0.80, 0.99), 0.83 (0.69, 1.00), 0.73 (0.63, 0.85), 0.84 (0.65, 1.08), and 0.79 (0.61, 1.03), respectively, for those time points, the cumulative probability of recurrence for the time points post-treatment, with an estimate at RR 5.28 (1.85, 15.12), 6.48 (2.46, 17.09), 9.67 (3.02, 30.99), 7.73 (2.81, 21.28), and 8.25 (3.01-22.62), respectively. CONCLUSION: We observed no significant differences between PDT and SE for the complete RR, but there was an increased cumulative probability of recurrence. More large-scale RCTs are required to verify our findings. PMID- 27363536 TI - Recent Advances in Imprinting Disorders. AB - Imprinting disorders (ImpDis) are a group of currently 12 congenital diseases with common underlying (epi)genetic etiologies and overlapping clinical features affecting growth, development and metabolism. In the last years it has emerged that ImpDis are characterized by the same types of mutations and epimutations, i.e. uniparental disomies, copy number variations, epimutations, and point mutations. Each ImpDis is associated with a specific imprinted locus, but the same imprinted region can be involved in different ImpDis. Additionally, even the same aberrant methylation patterns are observed in different phenotypes. As some ImpDis share clinical features, clinical diagnosis is difficult in some cases. The advances in molecular and clinical diagnosis of ImpDis help to circumvent these issues, and they are accompanied by an increasing understanding of the pathomechanism behind them. As these mechanisms have important roles for the etiology of other common conditions, the results in ImpDis research have a wider effect beyond the borders of ImpDis. For patients and their families, the growing knowledge contributes to a more directed genetic counseling of the families and personalized therapeutic approaches. PMID- 27363538 TI - Multifaceted Breast Cancer: The Molecular Connection With Obesity. AB - Obesity is characterized by a disruption in energy balance regulation that results in an excess accumulation of body fat. Its increasing prevalence poses a major public health concern because it is a risk factor for a host of additional chronic conditions, including type 2 diabetes, hypertension, and cardiovascular disease. Obesity is increasingly recognized as a growing cause of cancer risk. In particular excessive adipose expansion during obesity causes adipose dysfunction and inflammation that can regulate tumor growth. In obesity, dysregulated systemic metabolism and inflammation induce hyperinsulinemia, hyperglycemia, dyslipidemia, and enhance sex hormone production with increased secretion of proinflammatory adipokine that impact breast cancer development and progression. This review describes how adipose inflammation that characterizes obesity is responsible of microenvironment to promote cancer, and discuss how steroid hormones, that are essential for the maintenance of the normal development, growth and differentiation of the cells, influence the induction and progression of breast cancer. J. Cell. Physiol. 232: 69-77, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27363537 TI - Protective effects of allicin on streptozotocin-induced diabetic nephropathy in rats. AB - BACKGROUND: Studies in animal models have shown that allicin, a major biologically active component of garlic, can play a role in the prevention of tissue fibrosis in the liver, lung and heart, mainly related to the inhibition of fibroblast proliferation, fibrogenic cytokine secretion and extracellular matrix synthesis. This study aimed to investigate the protective effects of allicin on renal damage in streptozotocin (STZ)-induced diabetic rats. STZ-induced diabetic rats were administered allicin (15, 30 and 45 mg . kg-1 . day-1 ) via daily intra-gastric gavage for 12 weeks. The levels of fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (sCr), lipid and 24 h urine albumin excretion (UAE) were measured at the end of weeks 4, 8 and 12. The renal histopathology and the expression levels of collagen I, transforming growth factor beta1 (TGF-beta1) and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) were measured using immunohistochemistry and/or western blotting. RESULTS: In 12 week STZ-induced diabetic rats, severe hyperglycemia and albuminuria were markedly developed. Treatment with allicin for 12 weeks ameliorated diabetes-induced morphological alterations of the kidney and decreased FBG, BUN, sCr, triglyceride (TG) and 24 h UAE in diabetic rats. The expression levels of collagen I, TGF-beta1 and p-ERK1/2 were significantly decreased by allicin treatment. CONCLUSION: These results suggested that allicin may play a protective role in diabetic nephropathy via the TGF-beta1/ERK pathway in diabetic rats. (c) 2016 Society of Chemical Industry. PMID- 27363539 TI - Comorbidities in difficult asthma are independent risk factors for frequent exacerbations, poor control and diminished quality of life. AB - BACKGROUND AND OBJECTIVE: Little is known about how comorbidities affect difficult asthma patients across different domains of asthma outcomes. We hypothesized that comorbidities in difficult asthma significantly influence asthma outcomes. METHODS: We analysed 90 consecutive patients who underwent systematic assessment at our hospital's difficult asthma clinic. Eight comorbidities were assessed in all patients. They were allergic rhinitis, chronic rhinosinusitis (CRS), gastroesophageal reflux disease, obesity, obstructive sleep apnoea, anxiety or depression, dysfunctional breathing (DB) and vocal cord dysfunction (VCD). Asthma outcomes examined were exacerbation frequency (>=3/year vs <3/year), asthma control using the Asthma Control Test (ACT) and quality of life using the Asthma Quality of Life Questionnaire (AQLQ). Multivariate logistic regression was performed for dichotomous outcomes and linear regression for continuous outcomes. Analyses were adjusted for lung function and absolute blood eosinophils. RESULTS: Increasing BMI was an independent risk factor for exacerbations (OR: 1.1, 95% CI: 1-1.1, P = 0.042), lower ACT score (beta coefficient: -0.25, 95% CI: -0.37 to -0.12, P < 0.001) and poorer AQLQ (beta coefficient: -0.05, 95% CI: -0.09 to -0.02, P = 0.006). DB predicted lower ACT (beta coefficient: -2.85, 95% CI: -5 to -0.7, P = 0.01) and AQLQ scores (beta coefficient: -0.73, 95% CI: -1.34 to -0.12, P = 0.02). Patients with CRS had more exacerbations (OR: 4, 95% CI: 1.5-10.9, P = 0.006). Patients with VCD had lower AQLQ scores (beta coefficient: -0.78, 95% CI: -1.38 to -0.18, P = 0.012). CONCLUSION: Comorbidities independently impact a broad spectrum of outcomes in difficult asthma. Systematic evaluation of these conditions is essential in difficult asthma. PMID- 27363540 TI - Technical Skills Required in Split Liver Transplantation. AB - The number of liver grafts obtained from a cadaver can be greatly increased with the application of split liver transplantation. In the last 10 years, pediatric waiting list mortality has been reduced significantly with the use of this form of liver transplantation, which has 2 major forms. In its most commonly used form, the liver can be transplanted into 1 adult and 1 child by splitting it into a right extended and a left lateral graft. For adult and pediatric recipients, the results of this procedure are comparable to those of whole-organ techniques. In another form, 2 hemi-grafts are obtained by splitting the liver, which can be transplanted into a medium-sized adult (the right side) and a large child/small adult (the left side). The adult liver graft pool is expanded through the process of full right/full left splitting; but it is also a critical technique when one considers the knowledge required of the potential anatomic variations and the high technical skill level needed. In this review, we provide some basic insights into the technical and anatomical aspects of these 2 forms of split liver transplantation and present an updated summary of both forms. PMID- 27363542 TI - Cunning metal core: efficiency/stability dilemma in metallated porphyrin based light-emitting electrochemical cells. AB - The syntheses, photophysical/electrochemical characterizations of different metallated porphyrins -i.e., Zn(2+), Pt(2+), Pd(2+), and Sn(4+) porphyrins - as well as their first application in light-emitting electrochemical cells are provided. A direct comparison demonstrates that depending on the metallation either efficient (Pt-por) or stable (Zn-por) devices are achieved, demonstrating that the choice of the metal core is a key aspect for future developments. PMID- 27363541 TI - Realized niche shift associated with the Eurasian charophyte Nitellopsis obtusa becoming invasive in North America. AB - Nitellopsis obtusa (starry stonewort) is a dioecious green alga native to Europe and Asia that has emerged as an aquatic invasive species in North America. Nitellopsis obtusa is rare across large portions of its native range, but has spread rapidly in northern-tier lakes in the United States, where it can interfere with recreation and may displace native species. Little is known about the invasion ecology of N. obtusa, making it difficult to forecast future expansion. Using ecological niche modeling we investigated environmental variables associated with invasion risk. We used species records, climate data, and remotely sensed environmental variables to characterize the species' multidimensional distribution. We found that N. obtusa is exploiting novel ecological niche space in its introduced range, which may help explain its invasiveness. While the fundamental niche of N. obtusa may be stable, there appears to have been a shift in its realized niche associated with invasion in North America. Large portions of the United States are predicted to constitute highly suitable habitat for N. obtusa. Our results can inform early detection and rapid response efforts targeting N. obtusa and provide testable estimates of the physiological tolerances of this species as a baseline for future empirical research. PMID- 27363543 TI - Effect of hydrogen on dynamic charge transport in amorphous oxide thin film transistors. AB - Hydrogen in zinc oxide based semiconductors functions as a donor or a defect de activator depending on its concentration, greatly affecting the device characteristics of oxide thin-film transistors (TFTs). Thus, controlling the hydrogen concentration in oxide semiconductors is very important for achieving high mobility and minimizing device instability. In this study, we investigated the charge transport dynamics of the amorphous semiconductor InGaZnO at various hydrogen concentrations as a function of the deposition temperature of the gate insulator. To examine the nature of dynamic charge trapping, we employed short pulse current-voltage and transient current-time measurements. Among various examined oxide devices, that with a high hydrogen concentration exhibits the best performance characteristics, such as high saturation mobility (10.9 cm(2) v(-1) s(-1)), low subthreshold slope (0.12 V/dec), and negligible hysteresis, which stem from low defect densities and negligible transient charge trapping. Our finding indicates that hydrogen atoms effectively passivate the defects in subgap states of the bulk semiconductor, minimizing the mobility degradation and threshold voltage instability. This study indicates that hydrogen plays a useful role in TFTs by improving the device performance and stability. PMID- 27363544 TI - Anderson-like alkoxo-polyoxovanadate clusters serving as unprecedented second building units to construct metal-organic polyhedra. AB - Unprecedented Anderson-like alkoxo-polyoxovanadate [V6O6(OCH3)9(MU6-SO4)(COO)3](2 ) polyanions can serve as 3-connected second building units (SBUs) that assemble with dicarboxylate or tricarboxylate ligands to form a new family of metal organic tetrahedrons of V4E6 and V4F4 type (V = vertex, E = edge, and F = face). To our knowledge, this alkoxo-polyoxovanadate-based SBU is the first ever reported. PMID- 27363545 TI - The Value of Repeated Clinical Observation Over Time. PMID- 27363546 TI - Mechanisms Distinguishing Irritability in Children and Adolescents. PMID- 27363547 TI - Stress, the Placenta, and Fetal Programming of Behavior: Genes' First Encounter With the Environment. PMID- 27363548 TI - A Framework for Extending Psychiatrists' Roles in Treating General Health Conditions. PMID- 27363549 TI - Sips of Conflict. PMID- 27363550 TI - Claiming Our Future. PMID- 27363551 TI - Response to the Presidential Address. PMID- 27363552 TI - Renee Binder, M.D., 142nd President, 2015-2016. PMID- 27363553 TI - The Role of Bilateral ECT When Right Unilateral ECT Is Inferior. PMID- 27363554 TI - Response to Kellner and Farber: Addressing Crossover of High-Dose Right Unilateral ECT to Bitemporal ECT. PMID- 27363556 TI - Response to Sarpal et al.: Importance of Neuroimaging Biomarkers for Treatment Development and Clinical Practice. PMID- 27363555 TI - In Support of Neuroimaging Biomarkers of Treatment Response in First-Episode Schizophrenia. PMID- 27363557 TI - Response to de la Fuente-Sandoval: Challenges Measuring GABA Levels in Patients With Psychosis. PMID- 27363558 TI - Potential Regional Differences in GABA Levels in Patients With Psychosis Compared With Control Subjects. PMID- 27363564 TI - Reports to the Membership. AB - The following are edited/abbreviated versions of the annual reports of the APA Secretary, Treasurer, CEO and Medical Director, Speaker, and Speaker-Elect and the chairpersons of the APA Committee on Bylaws, Membership Committee, Committee of Tellers, and Elections Committee. The full reports were presented at the APA Annual Business Meeting in Atlanta, May 15th, 2016. PMID- 27363559 TI - CORRECTION. PMID- 27363565 TI - Volumetric Light-Field Excitation. AB - We explain how to concentrate light simultaneously at multiple selected volumetric positions by means of a 4D illumination light field. First, to select target objects, a 4D imaging light field is captured. A light field mask is then computed automatically for this selection to avoid illumination of the remaining areas. With one-photon illumination, simultaneous generation of complex volumetric light patterns becomes possible. As a full light-field can be captured and projected simultaneously at the desired exposure and excitation times, short readout and lighting durations are supported. PMID- 27363566 TI - Unbreakable distributed storage with quantum key distribution network and password-authenticated secret sharing. AB - Distributed storage plays an essential role in realizing robust and secure data storage in a network over long periods of time. A distributed storage system consists of a data owner machine, multiple storage servers and channels to link them. In such a system, secret sharing scheme is widely adopted, in which secret data are split into multiple pieces and stored in each server. To reconstruct them, the data owner should gather plural pieces. Shamir's (k, n)-threshold scheme, in which the data are split into n pieces (shares) for storage and at least k pieces of them must be gathered for reconstruction, furnishes information theoretic security, that is, even if attackers could collect shares of less than the threshold k, they cannot get any information about the data, even with unlimited computing power. Behind this scenario, however, assumed is that data transmission and authentication must be perfectly secure, which is not trivial in practice. Here we propose a totally information theoretically secure distributed storage system based on a user-friendly single-password-authenticated secret sharing scheme and secure transmission using quantum key distribution, and demonstrate it in the Tokyo metropolitan area (<=90 km). PMID- 27363568 TI - AMPA Receptor Positive Allosteric Modulators: Potential for the Treatment of Neuropsychiatric and Neurological Disorders. AB - The neurotransmitter glutamate and its receptors have long been of interest to scientists involved in pharmaceutical research since dysfunction of the glutamatergic signalling pathway has been associated with the pathophysiology of several psychiatric and neurological disorders. The research on AMPAR positive allosteric modulators offers opportunities to modulate fast excitatory synaptic transmission and identify new potential therapeutic agents for a range of neurodiseases. The field of AMPAR modulators continues to be a dynamic area of drug discovery with a pronounced diversification of the chemotypes explored in recent years. This article reviews literature published in this area in the last 6 years, focusing on the new core templates, some derived from high-throughput screens, with an emphasis on structure-activity relationships, drug metabolism and pharmacokinetics properties, and pharmacological profiles of these series. PMID- 27363567 TI - Micronutrient intake and food sources in the very old: analysis of the Newcastle 85+ Study. AB - A number of socio-economic, biological and lifestyle characteristics change with advancing age and place very old adults at increased risk of micronutrient deficiencies. The aim of this study was to assess vitamin and mineral intakes and respective food sources in 793 75-year-olds (302 men and 491 women) in the North East of England, participating in the Newcastle 85+ Study. Micronutrient intakes were estimated using a multiple-pass recall tool (2*24 h recalls). Determinants of micronutrient intake were assessed with multinomial logistic regression. Median vitamin D, Ca and Mg intakes were 2.0 (interquartile range (IQR) 1.2-6.5) ug/d, 731 (IQR 554-916) mg/d and 215 (IQR 166-266) mg/d, respectively. Fe intake was 8.7 (IQR 6.7-11.6) mg/d, and Se intake was 39.0 (IQR 27.3-55.5) ug/d. Cereals and cereal products were the top contributors to intakes of folate (31.5 %), Fe (49.2 %) and Se (46.7 %) and the second highest contributors to intakes of vitamin D (23.8 %), Ca (27.5 %) and K (15.8 %). More than 95 % (n 756) of the participants had vitamin D intakes below the UK's Reference Nutrient Intake (10 ug/d). In all, >20 % of the participants were below the Lower Reference Nutrient Intake for Mg (n 175), K (n 238) and Se (n 418) (comparisons with dietary reference values (DRV) do not include supplements). As most DRV are not age specific and have been extrapolated from younger populations, results should be interpreted with caution. Participants with higher education, from higher social class and who were more physically active had more nutrient-dense diets. More studies are needed to inform the development of age-specific DRV for micronutrients for the very old. PMID- 27363569 TI - Increasing the Impact of Peer-Reviewed Publications Through Tailored Dissemination Strategies: Perspectives for Practice Feature in JOSPT. AB - Peer-reviewed research manuscripts published by JOSPT and similar journals are a cornerstone of the health research "system." They are a critical mechanism through which researchers share their findings with interested readers. A limitation of peer-reviewed publications, however, is their ability to convey important findings to nonresearcher readers in a way that is meaningful and practical to them. In recognition of these persisting "research-to-action gaps," the field of knowledge translation has emerged. To optimize knowledge transfer, a more active dissemination approach that tailors the message and format to each specific audience is required. It is with this focus that JOSPT has launched a new feature targeted at rehabilitation clinicians, titled Perspectives for Practice. We look forward to continuing to develop and evaluate this feature in forthcoming issues. J Orthop Sports Phys Ther 2016;46(7):500-501. doi:10.2519/jospt.2016.0110. PMID- 27363570 TI - Clinical Prediction Rules That Don't Hold Up-Where to Go From Here? AB - Clinical prediction rules (CPRs) are created to help guide clinical decision making. To do this, they use the presence or absence of certain factors that have been shown to meaningfully predict a patient's prognosis, diagnosis, or response to treatment. While representing a seminal methodological step forward in individualized care, one of the main drawbacks of CPRs continues to be validation studies that do not support the initially derived CPR. This is particularly important because validation of CPRs in an independent patient population prior to clinical implementation is essential. Why is it quite common for existing CPRs to fall down at the validation stage? And what does this mean for research that aims to individualize treatment? J Orthop Sports Phys Ther 2016;46(7):502-505. doi:10.2519/jospt.2016.0606. PMID- 27363571 TI - Physical Agents for Soft Tissue Injury. AB - The clinical management of soft tissue injuries of the lower limb commonly includes physical agents such as electrotherapy or ultrasound. However, the evidence about the effectiveness of physical agents varies, and their use remains controversial. A systematic review of randomized clinical trials (RCTs), published in the July 2016 issue of JOSPT, examined the benefits and safety risks of various physical agents for soft tissue injuries of the lower limb. Importantly, the review looked closely at the quality of the RCTs and focused on studies with low risk of bias. In this Perspectives for Practice, the authors explain the impact of their findings for clinicians treating patients with such musculoskeletal conditions. J Orthop Sports Phys Ther 2016;46(7):555. doi:10.2519/jospt.2016.0503. PMID- 27363572 TI - Behavior of the Linea Alba During a Curl-up Task in Diastasis Rectus Abdominis: An Observational Study. AB - Study Design Cross-sectional repeated measures. Background Rehabilitation of diastasis rectus abdominis (DRA) generally aims to reduce the inter-rectus distance (IRD). We tested the hypothesis that activation of the transversus abdominis (TrA) before a curl-up would reduce IRD narrowing, with less linea alba (LA) distortion/deformation, which may allow better force transfer between sides of the abdominal wall. Objectives This study investigated behavior of the LA and IRD during curl-ups performed naturally and with preactivation of the TrA. Methods Curl-ups were performed by 26 women with DRA and 17 healthy control participants using a natural strategy (automatic curl-up) and with TrA preactivation (TrA curl-up). Ultrasound images were recorded at 2 points above the umbilicus (U point and UX point). Ultrasound measures of IRD and a novel measure of LA distortion (distortion index: average deviation of the LA from the shortest path between the recti) were compared between 3 tasks (rest, automatic curl-up, TrA curl-up), between groups, and between measurement points (analysis of variance). Results Automatic curl-up by women with DRA narrowed the IRD from resting values (mean U-point between-task difference, -1.19 cm; 95% confidence interval [CI]: -1.45, -0.93; P<.001 and mean UX-point between-task difference, 0.51 cm; 95% CI: -0.69, -0.34; P<.001), but LA distortion increased (mean U-point between-task difference, 0.018; 95% CI: 0.0003, 0.041; P = .046 and mean UX-point between-task difference, 0.025; 95% CI: 0.004, 0.045; P = .02). Although TrA curl up induced no narrowing or less IRD narrowing than automatic curl-up (mean U point difference between TrA curl-up versus rest, -0.56 cm; 95% CI: -0.82, -0.31; P<.001 and mean UX-point between-task difference, 0.02 cm; 95% CI: -0.22, 0.19; P = .86), LA distortion was less (mean U-point between-task difference, -0.025; 95% CI: -0.037, -0.012; P<.001 and mean UX-point between-task difference, -0.021; 95% CI: -0.038, -0.005; P = .01). Inter-rectus distance and the distortion index did not change from rest or differ between tasks for controls (P>=.55). Conclusion Narrowing of the IRD during automatic curl-up in DRA distorts the LA. The distortion index requires further validation, but findings imply that less IRD narrowing with TrA preactivation might improve force transfer between sides of the abdomen. The clinical implication is that reduced IRD narrowing by TrA contraction, which has been discouraged, may positively impact abdominal mechanics. J Orthop Sports Phys Ther 2016;46(7):580-589. doi:10.2519/jospt.2016.6536. PMID- 27363573 TI - Bunion: Strengthening Foot Muscles to Reduce Pain and Improve Mobility. AB - Foot pain discourages physical activity, and less activity harms overall health. Bunion, extra bone and tissue at the base of the big toe, is a frequent cause of foot pain. More than 64 million Americans have bunions that can lead to painful walking. Bunions affect some 35% of women over the age of 65. Bunions can be removed by surgery, which can reduce pain and improve your ability to walk and exercise, but up to 15% of bunions return. Weak muscles may play a role in bunion related pain and movement problems. In a review of prior research and commentary on this topic published in the July 2016 issue of JOSPT, the author identifies muscle-strengthening exercises that may help people with bunions. J Orthop Sports Phys Ther 2016;46(7):606. doi:10.2519/jospt.2016.0504. PMID- 27363574 TI - Benign Vascular Malformation at the Ischial Tuberosity. AB - A 31-year-old female student was referred to physical therapy with a chief complaint of proximal, posterior left thigh pain that began insidiously 12 months prior, and progressively worsened while training for a half-marathon. A mobile, soft mass was identified just inferior to the ischial tuberosity that was tender and painful to palpation, recreating the patient's chief complaint. Radiographic findings were negative for a suspected avulsion fracture at the ischial tuberosity. Therefore, the physician performed musculoskeletal ultrasonography, which revealed a superficial hypoechoic mass with vascular flow. Magnetic resonance imaging and a subsequent biopsy led to the diagnosis of a benign vascular malformation. J Orthop Sports Phys Ther 2016;46(7):607. doi:10.2519/jospt.2016.0410. PMID- 27363575 TI - Fibular Fracture in a Female Rugby Player. AB - A 20-year-old female rugby player was injured when an opponent landed on her leg during a match. Twelve days after injury, the team's certified athletic trainer referred the patient to a physical therapist due to continued pain. Following fluoroscopic imaging, which was utilized by the physical therapist because standard radiographs were unavailable in close proximity, she was referred for radiographs, which demonstrated a midfibular diaphyseal fracture. J Orthop Sports Phys Ther 2016;46(7):608. doi:10.2519/jospt.2016.0411. PMID- 27363577 TI - Diagnosis of Basal Cell Carcinoma by Reflectance Confocal Microscopy: Study Design and Protocol of a Randomized Controlled Multicenter Trial. AB - BACKGROUND: Skin cancer, including basal cell carcinoma (BCC), has become a major health care problem. The limitations of a punch biopsy (at present the gold standard) as diagnostic method together with the increasing incidence of skin cancer point out the need for more accurate, cost-effective, and patient friendly diagnostic tools. In vivo reflectance confocal microscopy (RCM) is a noninvasive imaging technique that has great potential for skin cancer diagnosis. OBJECTIVE: To investigate whether in vivo RCM can correctly identify the subtype of BCC and to determine the cost-effectiveness of RCM compared with punch biopsy (usual care). STUDY DESIGN: Randomized controlled multicenter trial. METHODS: On the basis of 80% power and an alpha of 0.05, 329 patients with lesions clinically suspicious for BCC will be included in this study. Patients will be randomized for RCM or for a punch biopsy (usual care). When a BCC is diagnosed, surgical excision will follow and a follow-up visit will be planned 3 months later. Several questionnaires will be filled in (EQ-5D, EQ-5D VAS, iMTA PCQ, and TSQM 9). We will perform statistical analysis, cost-effectiveness, and patient outcome analysis after data collection. RESULTS: This research started in January 2016 and is ethically approved. We expect to finish this study at the end of 2018. CONCLUSIONS: In this study, we will investigate whether RCM is at least as good in identifying BCC subtypes as conventional pathological investigation of skin biopsies. Anticipating that RCM is found to be a cost-effective alternative, it saves on direct medical consumption like labor of the pathologist and other medical personnel as well as materials related to treatment failure with at least equal effectiveness. TRIAL REGISTRATION: Clinicaltrials.gov NCT02623101; https://clinicaltrials.gov/ct2/show/NCT02623101 (Archived by WebCite at http://www.webcitation.org/6id54WQa2). PMID- 27363576 TI - Transmission of alpha-synucleinopathy from olfactory structures deep into the temporal lobe. AB - BACKGROUND: alpha-synucleinopathy emerges quite early in olfactory structures such as the olfactory bulb and anterior olfactory nucleus (OB/AON) in Parkinson's disease. This may contribute to smell impairments years before the commencement of motor symptoms. We tested whether alpha-synucleinopathy can spread from the OB/AON to regions of the limbic telencephalon that harbor connections with olfactory structures. FINDINGS: alpha-synuclein fibrils were infused into the OB/AON. Inclusions containing pathologically phosphorylated alpha-synuclein (pSer129) were observed three months later in the piriform and entorhinal cortices, amygdala, and hippocampal formation. The retrograde tract-tracer FluoroGold confirmed the existence of first-order afferents at these sites. Some sites harbored FluoroGold(+) neurons but no inclusions, suggestive of selective vulnerabilities. Multiple areas close to the injection site but not connected with the OB/AON remained free of inclusions, suggesting a lack of widespread uptake of fibrils from interstitial diffusion. Two independent pSer129 antibodies revealed the same labeling patterns and preadsorption control experiments confirmed a loss of pSer129 staining. Dense total alpha-synuclein (but not pSer129) staining was apparent in the OB/AON 1.5 h following fibril infusions, suggesting that pSer129(+) staining did not reflect exogenously infused material. Waterbath sonication of fibrils for 1 h improved alpha-synucleinopathy transmission relative to 1 min-long probe sonication. Electron microscopy revealed that longer sonication durations reduced fibril size. The Thioflavin stain labeled cells at the infusion site and some, but not all inclusions contained ubiquitin. Three-dimensional confocal analyses revealed that many inclusions ensconced NeuN(+) neuronal nuclei. Young and aged mice exhibited similar topographical spread of alpha-synucleinopathy. CONCLUSIONS: 1) alpha synucleinopathy in this model is transmitted through some, but not all neuroanatomical connections, 2) pathology is largely confined to first-order afferent sites at three months and this is most parsimoniously explained by retrograde transport, and 3) transmission in aged animals is largely similar to that in young control animals at three months post-infusion. PMID- 27363578 TI - Efficacy and safety of using a warming needle for persistent allergic rhinitis: study protocol for a randomized controlled trial. AB - BACKGROUND: Many previous studies have shown the potential therapeutic effect of acupuncture for allergic rhinitis. Most of these studies, however, were limited by the short duration of observations and lack of sham acupuncture as the control group. Our preliminary experiments showed that the use of a warm needling achieved a much more persistent effect in the treatment of allergic rhinitis (AR) compared with simple acupuncture therapy. Hence, we have designed a multicenter, randomized controlled trial (RCT) in which the first-line medication loratadine will be used as the control group, and the effect of warm needling therapy will be evaluated through long-term observation. METHODS/DESIGN: The trial is designed as a multicenter, parallel-group, randomized, single-blinded (outcome assessors), non-inferiority trial. A total of 98 patients with persistent AR will be randomly assigned into two groups. Patients in the treatment group will be treated with warm needling at GV14 and acupuncture at EX-HN3, ST2, LI20, EX-HN8, GV23, LU7, LU5 and LI4 three times a week, for a total of 4 weeks. Patients in the control group will be treated with oral loratadine 10 mg/day for 4 weeks. The primary outcome will be the change in the Total Nasal Symptom Score (TNSS) from baseline to that at 6 months after treatment during the follow-up period. The secondary outcomes will include the Total Non-nasal Symptom Score and the Rhinoconjunctivitis Quality of Life Questionnaire, changes in the TNSS from baseline to that at 2 and 4 weeks during treatment, and 3 months after treatment during the follow-up period. Outcomes will be measured at 2 and 4 weeks, and 3 and 6 months after treatment. Any side effects of treatment will be observed and recorded. DISCUSSION: We expect that the study results will provide evidence to determine the effects of warm needling compared with loratadine. Our final goal of the study is to evaluate the difference in the short-term and long-term effects between the two therapeutic methods, especially the long-term effect of warm needling. TRIAL REGISTRATION: ClinicalTrials.gov NCT02339714 . Registered on 14 January 2015. PMID- 27363579 TI - Enhanced excitability and suppression of A-type K(+) currents in joint sensory neurons in a murine model of antigen-induced arthritis. AB - Pain is a dominant symptom of rheumatoid arthritis (RA) and its adequate treatment represents a major unmet need. However, the cellular mechanisms that drive arthritis pain are largely unexplored. Here, we examined the changes in the activity of joint sensory neurons and the associated ionic mechanisms using an animal model of antigen-induced arthritis (AIA). Methylated-bovine serum albumin (mBSA), but not vehicle challenge, in the ankle of previously immunized mice produced time-dependent symptoms of arthritis, including joint inflammation, primary mechanical hyperalgesia in the ipsilateral ankle, and secondary mechanical and heat hyperalgesia in the ipsilateral hindpaw. In vivo electrophysiological recordings revealed that Dil-labeled joint sensory neurons in AIA mice exhibited a greater incidence of spontaneous activity, mechanically evoked after-discharges, and/or increased responses to mechanical stimulation of their receptive fields, compared to control animals. Whole-cell recordings in vitro showed that AIA enhanced the excitability of joint sensory neurons. These signs of neuronal hyperexcitability were associated with a significant reduction in the density of A-type K(+) currents. Thus, our data suggest that neuronal hyperexcitability, brought about in part by reduced A-type K(+) currents, may contribute to pain-related behaviors that accompany antigen-induced arthritis and/or other antigen-mediated diseases. PMID- 27363580 TI - Inhibition of hypoxia inducible factor-1alpha attenuates abdominal aortic aneurysm progression through the down-regulation of matrix metalloproteinases. AB - Hypoxia inducible factor-1alpha (HIF-1alpha) pathway is associated with many vascular diseases, including atherosclerosis, arterial aneurysms, pulmonary hypertension and chronic venous diseases. Significant HIF-1alpha expression could be found at the rupture edge at human abdominal aortic aneurysm (AAA) tissues. While our initial in vitro experiments had shown that deferoxamine (DFO) could attenuate angiotensin II (AngII) induced endothelial activations; we unexpectedly found that DFO augmented the severity of AngII-induced AAA, at least partly through increased accumulation of HIF-1alpha. The findings promoted us to test whether aneurysmal prone factors could up-regulate the expression of MMP-2 and MMP-9 through aberrantly increased HIF-1alpha and promote AAA development. AngII induced AAA in hyperlipidemic mice model was used. DFO, as a prolyl hydroxylase inhibitor, stabilized HIF-1alpha and augmented MMPs activities. Aneurysmal-prone factors induced HIF-1alpha can cause overexpression of MMP-2 and MMP-9 and promote aneurysmal progression. Pharmacological HIF-1alpha inhibitors, digoxin and 2-ME could ameliorate AngII induced AAA in vivo. HIF-1alpha is pivotal for the development of AAA. Our study provides a rationale for using HIF-1alpha inhibitors as an adjunctive medical therapy in addition to current cardiovascular risk-reducing regimens. PMID- 27363582 TI - Nanoscale electrical properties of epitaxial Cu3Ge film. AB - Cu3Ge has been pursued as next-generation interconnection/contact material due to its high thermal stability, low bulk resistivity and diffusion barrier property. Improvements in electrical performance and structure of Cu3Ge have attracted great attention in the past decades. Despite the remarkable progress in Cu3Ge fabrication on various substrates by different deposition methods, polycrystalline films with excess Ge were frequently obtained. Moreover, the characterization of nanoscale electrical properties remains challenging. Here we show the fabrication of epitaxial Cu3Ge thin film and its nanoscale electrical properties, which are directly correlated with localized film microstructures and supported by HRTEM observations. The average resistivity and work function of epitaxial Cu3Ge thin film are measured to be 6 +/- 1 MUOmega cm and ~4.47 +/- 0.02 eV respectively, qualifying it as a good alternative to Cu. PMID- 27363581 TI - Ligand-binding domains of nuclear receptors facilitate tight control of split CRISPR activity. AB - Cas9-based RNA-guided nuclease (RGN) has emerged to be a versatile method for genome editing due to the ease of construction of RGN reagents to target specific genomic sequences. The ability to control the activity of Cas9 with a high temporal resolution will facilitate tight regulation of genome editing processes for studying the dynamics of transcriptional regulation or epigenetic modifications in complex biological systems. Here we show that fusing ligand binding domains of nuclear receptors to split Cas9 protein fragments can provide chemical control over split Cas9 activity. The method has allowed us to control Cas9 activity in a tunable manner with no significant background, which has been challenging for other inducible Cas9 constructs. We anticipate that our design will provide opportunities through the use of different ligand-binding domains to enable multiplexed genome regulation of endogenous genes in distinct loci through simultaneous chemical regulation of orthogonal Cas9 variants. PMID- 27363583 TI - Active surveillance scheme in three Romanian hospitals reveals a high prevalence and variety of carbapenamase-producing Gram-negative bacteria: a pilot study, December 2014 to May 2015. AB - We report the findings of an active surveillance scheme for detection of asymptomatic carriers with carbapenemase-producing Gram-negative bacteria (CP GNB) in Romanian hospitals. During a pilot study from December 2014 to May 2015, faecal cultures were screened in three hospitals (two large, one medium-size) for patients newly admitted to selected wards or inpatients transferred from other wards to an intensive-care unit. The study revealed a high prevalence of CP-GNB detected in 22/27 and 28/38 of the carbapenem non-susceptible isolates from Hospitals 1 and 3, respectively. CP-GNB identified through faecal screening included NDM-1-producing Serratia marcescens and Klebsiella pneumoniae, OXA-48 producing K. pneumoniae and OXA-23-producing Acinetobacter baumannii. The distribution of the CP-GNB varied between the hospitals, with NDM-1-producing S. marcescens and K. pneumoniae being prevalent in the north-central part of the country and OXA-23/24-producing A. baumannii, OXA-48-producing K.pneumoniae, Morganella morganii and VIM-2-producing Escherichia coli/Pseudomonas aeruginosa detected in the north-east of the country. Conjugation studies showed that carbapenem resistance was transferable and PCR-based replicon typing identified blaNDM-1 on IncFIIs in S. marcescens and K. pneumoniae from Hospital 1 and blaOXA 48 on IncL plasmids in all Klebsiella spp. isolates from Hospitals 1 and 3. Our findings underline the importance of active surveillance for detection of CP-GNB asymptomatic faecal carriers and suggest a likely endemic spread of CP-GNB in Romania. PMID- 27363584 TI - Treatment of bisphosphonate-related osteonecrosis of the jaw using platelet-rich fibrin. AB - BACKGROUND: Bisphosphonates are commonly prescribed antiresorptive agents for the management of patients with osteoporosis, Paget's disease, multiple myeloma, and metastatic tumors. Platelet-rich fibrin (PRF) is a second generation platelet concentrate, and has the ability of regulating the inflammation and stimulation of chemotactic agents. The aim of this report is to present the treatment of Stage-3 bisphosphonate-related osteonecrosis of the jaw (BRONJ) by PRF. CLINICAL PRESENTATION: A 77-year-old male patient with Stage-3 BRONJ was treated with minimal surgical operations and PRF membrane. The patient was followed up for 18 months, and there was no recurrence or exposure. CONCLUSION: PRF may promote the healing of both bone and soft tissues even in Stage-3 patients. This technique is an alternative treatment modality for the closure of bone exposure and tissue healing in BRONJ patients. PMID- 27363586 TI - 'Now it is about me having to learn something ....' Partners' experiences with a Dutch conversation partner training programme (PACT). AB - BACKGROUND: The increase in the number of reported conversation partner programmes for conversation partners of people with aphasia demonstrates increased awareness of partner needs and the positive effect of trained partners on the communicative abilities of the person with aphasia. Predominantly small scale studies describe the effectiveness of conversation partner training (CPT) and how partners perceive this training. The view of partners on this service commission remains largely unknown. AIMS: To explore the experiences of partners of people with aphasia with a CPT programme when it was newly introduced into rehabilitation settings. METHODS & PROCEDURES: Seventeen partners of people with aphasia were interviewed using a semi-structured format about their experience with Partners of Aphasic Clients Conversation Training (PACT). Transcribed interviews were analysed using qualitative content analysis. OUTCOMES & RESULTS: Four categories representative of the practical nature and individual tailoring of PACT were identified: engaging with PACT; learning from PACT; reflecting on behaviour and emotions; and experiences with earlier speech and language therapy (SLT). Two themes were identified cutting across all categories: the nature of communication is difficult to grasp; and balancing roles as partner, carer and client. CONCLUSIONS & IMPLICATIONS: Partners appreciated the training programme once their initial lack of awareness of the interactive nature of communication had been addressed. SLTs need to be clear about the collaborative nature of conversations and what can be offered within the rehabilitation trajectory to address conversation alongside language training. PMID- 27363585 TI - De novo frameshift mutation in COUP-TFII (NR2F2) in human congenital diaphragmatic hernia. AB - COUP-TFII (NR2F2) is mapped to the 15q26 deletion hotspot associated with the common and highly morbid congenital diaphragmatic hernia (CDH). Conditional homozygous deletions of COUP-TFII in mice result in diaphragmatic defects analogous to the human Bochdalek-type hernia phenotype. Despite evidence from animal models however, mutations in the coding sequence of COUP-TFII have not been reported in patients, prompting the speculation that additional coding or non-coding sequences in the 15q26 locus are necessary for diaphragmatic hernias to develop. In this report, we describe a case of a patient with a heterozygous de novo COUP-TFII frameshift mutation, presenting with CDH and an atrial septal defect. The p.Pro33AlafsTer77 mutation specifically disrupts protein isoform 1 which contains the DNA binding domain. In addition, we review other COUP-TFII sequence variations and deletions that have been described in cases of CDH. We conclude that COUP-TFII mutations can cause diaphragmatic hernias, and should be included in the differential diagnosis of CDH patients, particularly those with comorbid congenital heart defects. (c) 2016 Wiley Periodicals, Inc. PMID- 27363588 TI - Chemically Non-Innocent Cyclic (Alkyl)(Amino)Carbenes: Ligand Rearrangement, C-H and C-F Bond Activation. AB - A cyclic (alkyl)(amino)carbene (CAAC) was found to undergo unprecedented rearrangements and transformations of its core structure in the presence of Group 1 and 2 metals. Although the carbene was also found to be prone to intramolecular C-H activation, it was competent for intermolecular activation of a variety of sp , sp(2) -, and sp(3) -hybridized C-H bonds. Double C-F activation of hexafluorobenzene was also observed in this work. These processes all hold relevance to the role of these carbenes in catalysis, as well as to their use in the synthesis of new and unusual main group or transition metal complexes. PMID- 27363587 TI - Liver stiffness measurement reliability and main determinants of point shear-wave elastography in patients with chronic liver disease. AB - BACKGROUND: Liver stiffness (LS) measured by transient elastography (TE) accurately predicts the severity of chronic liver diseases (CLD). Point quantification shear-wave elastography (pSWE) is a new technique incorporated into a conventional ultrasound system for measuring LS. We evaluated pSWE feasibility, reproducibility and diagnostic accuracy in consecutively recruited CLD patients who concomitantly underwent TE and liver biopsy. AIM: To evaluate pSWE feasibility, reproducibility and diagnostic accuracy in consecutively recruited CLD patients who concomitantly underwent TE and liver biopsy. METHODS: Over 2 years 186 CLD patients (116 males, 132 viral hepatitis) consecutively underwent pSWE (10 valid measurements by ElastPQ) blindly performed by two raters. A further operator performed TE. Inter-observer agreement for pSWE was analysed by intraclass correlation coefficient (ICC) and correlated with histological liver fibrosis (METAVIR). Main determinants of pSWE were investigated by linear regression model. RESULTS: Three hundred and seventy-two (100%) reliable measurements were obtained by pSWE and 184 by TE (99%). LS was 8.1 +/- 4.5 kPa for pSWE with the first rater and 8.0 +/- 4.2 kPa with the second one vs. 8.8 +/- 3.6 kPa for TE. pSWE ICC was 0.89 (95% CI 0.85-0.91), not influenced by age, sex, BMI, liver enzymes, liver aetiology. ICC increased over time with year 1 at 0.86 and 95% CI 0.81-0.90 vs. year 2 at 0.92 and 95% CI 0.87 0.95. Liver fibrosis was the only independent determinant of LS on pSWE. The AUROCs for diagnosing F >= 2, F >= 3 and F = 4 were 0.77, 0.85 and 0.88 for pSWE vs. 0.81, 0.88 and 0.94 for TE. After 1-year training they were 0.86, 0.94 and 0.91. CONCLUSION: Point quantification shear-wave elastography reliably and reproducibly evaluates liver stiffness, matching transient elastography for accuracy after a 1-year learning curve or 130 examinations. PMID- 27363589 TI - Longitudinal follow-up of levator ani muscle avulsion: does a second delivery affect it? AB - OBJECTIVES: To evaluate the morphological outcome of levator ani muscle (LAM) avulsion 3-5 years after a first delivery and to assess the effect of a second delivery on this condition. The impact of LAM avulsion on pelvic floor disorders was also studied. METHODS: Six hundred and sixty-six women who had been assessed for LAM avulsion 8 weeks after their first delivery were invited for a follow-up examination 3-5 years later. Women completed the Pelvic Floor Distress Inventory including the Urinary Distress Inventory (UDI) and Pelvic Organ Prolapse Distress Inventory (POPDI) questionnaires to explore symptoms of pelvic floor disorders, and the pelvic floor was examined using three-dimensional translabial ultrasound and assessed using the pelvic organ prolapse quantification system. RESULTS: Three hundred and ninety-nine women completed the study, of whom 151 were multiparous. Mean interval between first delivery and follow-up was 42.3 +/- 7.6 months. Among 69 women who had LAM avulsion 8 weeks after their first delivery, nine (13.0%) had no LAM avulsion at follow-up. One (0.9%) woman had a new LAM avulsion after her second vaginal delivery. A greater proportion of women with LAM avulsion reported symptoms of stress urinary incontinence (SUI) (adjusted odds ratio, 2.09 (95% CI, 1.18-3.70); P = 0.01) and symptoms of prolapse than did women without avulsion; however, this difference did not reach statistical significance (P = 0.61). Women with LAM avulsion had higher UDI and POPDI scores than did women without avulsion (median UDI score, 17.7 (interquartile range (IQR), 5.0-32.4) vs 9.2 (IQR, 0.0-22.1); P = 0.045 and median POPDI score, 20.8 (IQR, 8.8-40.5) vs 10.7 (IQR, 0.0-32.8); P = 0.021). CONCLUSIONS: The risk of developing new LAM avulsion after a second vaginal delivery is low (0.9%). Healing of LAM avulsion was observed in 13% of women who had at least one vaginal delivery. At 3-5 years after delivery, women with LAM avulsion reported symptoms of SUI more often than did those without, and had higher UDI and POPDI scores, implying more bothersome symptoms. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27363590 TI - UK government should fund stop smoking media campaigns not give tax breaks to films with smoking imagery. PMID- 27363591 TI - Prospective cohort study evaluating risk factors for the development of pasture associated laminitis in the United Kingdom. AB - BACKGROUND: Certain individuals appear to be predisposed to recurrent pasture associated laminitis. Previous studies have predominantly investigated risk factors only after disease occurrence. OBJECTIVES: To investigate risk factors for pasture-associated laminitis prior to disease occurrence. STUDY DESIGN: Prospective cohort study. METHODS: Non-laminitic ponies aged >=7 years were recruited. Body condition score (BCS), height, weight, crest height and thickness were measured and an overnight dexamethasone suppression test performed. Plasma or serum adiponectin, leptin, triglyceride, basal insulin, insulin post dexamethasone, insulin-like growth factor 1 (IGF-1), IGF binding protein 1 (IGFBP 1), IGFBP-3, C-reactive protein, von Willebrand's factor, soluble E-selectin and P-selectin concentrations were assayed. Follow-up data were obtained from owners annually for 3 years to ascertain occurrences of veterinarian-diagnosed pasture associated laminitis. Data were analysed by multivariate logistic regression. Receiver operating characteristic (ROC) curves analysis was performed for significant risk factors and cut-off values determined. RESULTS: A total of 446 animals with a median (interquartile range) age of 15 (10-20) years were recruited. Of these, 50.4% were mares and 49.6% were geldings. The most common breeds were Welsh (36.4%), Shetland (17.0%) and cob (9.4%). Overall, 72.2% of animals were overweight/obese (BCS 7-9/9), 27.3% were of ideal weight (BCS 4-6/9) and 0.5% were underweight (BCS 1-3/9). After 1, 2 and 3 years, respectively, 18 (4.0%), 30 (6.7%) and 44 (9.9%) animals were reported to have had laminitis. Plasma adiponectin, and serum basal (insulin) and (insulin) post-dexamethasone levels were significantly (P <= 0.05) associated with laminitis occurrence cumulatively after 1, 2 and 3 years. Use of the area under the ROC curves to distinguish animals that did and did not develop laminitis showed good (basal [insulin] after 1 year), fair (all others) or poor ([insulin] post-dexamethasone) levels of accuracy. MAIN LIMITATIONS: Animals were evaluated at a single time point and biomarkers were assayed using single assays. CONCLUSIONS: Risk factors for future laminitis prior to disease occurrence include low plasma adiponectin and high serum basal insulin or insulin post-dexamethasone concentrations. PMID- 27363592 TI - Variations in the Genome: The Mutation Detection 2015 Meeting on Detection, Genome Sequencing, and Interpretation. AB - The content of the 13th Mutation Detection meeting (Leiden, April 2015) is summarized in this report. Topics discussed at the meeting included current challenges of clinical NGS, advances in bioinformatics, data quality control, single cell analysis and RNA sequencing, among others. Social, ethical and regulatory challenges of genomic data handling and data sharing were the focus of an expert panel debate. The 14th International Symposium on Variants in the Genome will take place in Santiago de Compostela, June 5-8, 2017. http://isv.variome.org. PMID- 27363594 TI - Controlled Aqueous Growth of Hematite Nanoplate Arrays Directly on Transparent Conductive Substrates and Their Photoelectrochemical Properties. AB - Two-dimensional (2D) hematite nanoplate arrays were synthesized directly on fluorine-doped tin oxide (FTO)-coated glass by using a facile and novel hydrothermal method. High-temperature annealing retained the morphology of the nanoplate arrays while simultaneously introducing porosity. The thickness and length of the nanoplates could be tailored by adjusting the precursor composition. Photoelectrochemical (PEC) measurements showed that the photocurrent generated with bare hematite nanoplate photoelectrode under backside illumination was about four times of that under frontside illumination in the entire bias range used, which suggested that slow electron transport was a limiting factor for its PEC performance. Upon Sn doping and Co-Pi co-catalyst addition, the photocurrent increased significantly owing to the enhancement of electron conductivity and oxidation kinetics. Electrochemical impedance spectroscopy (EIS) measurements were conducted to understand the surface properties of the nanoplate arrays. Since this strategy is simple, cost-effective, and highly reproducible, it provides exciting opportunities for the large-scale growth of porous 2D metal oxide photoelectrodes for a variety of photoelectrochemical and photocatalytic applications. PMID- 27363593 TI - A pleiotropic interaction between vision loss and hypermelanism in Astyanax mexicanus cave x surface hybrids. AB - BACKGROUND: Cave-dwelling animals evolve various traits as a consequence of life in darkness. Constructive traits (e.g., enhanced non-visual sensory systems) presumably arise under strong selective pressures. The mechanism(s) driving regression of features, however, are not well understood. Quantitative trait locus (QTL) analyses in Astyanax mexicanus Pachon cave x surface hybrids revealed phenotypic effects associated with vision and pigmentation loss. Vision QTL were uniformly associated with reductions in the homozygous cave condition, however pigmentation QTL demonstrated mixed phenotypic effects. This implied pigmentation might be lost through both selective and neutral forces. Alternatively, in this report, we examined if a pleiotropic interaction may exist between vision and pigmentation since vision loss has been shown to result in darker skin in other fish and amphibian model systems. RESULTS: We discovered that certain members of Pachon x surface pedigrees are significantly darker than surface-dwelling fish. All of these "hypermelanic" individuals demonstrated severe visual system malformations suggesting they may be blind. A vision-mediated behavioral assay revealed that these fish, in stark contrast to surface fish, behaved the same as blind cavefish. Further, hypermelanic melanophores were larger and more dendritic in morphology compared to surface fish melanophores. However, hypermelanic melanophores responded normally to melanin-concentrating hormone suggesting darkening stemmed from vision loss, rather than a defect in pigment cell function. Finally, a number of genomic regions were coordinately associated with both reduced vision and increased pigmentation. CONCLUSIONS: This work suggests hypermelanism in hybrid Astyanax results from blindness. This finding provides an alternative explanation for phenotypic effect studies of pigmentation QTL as stemming (at least in part) from environmental, rather than exclusively genetic, interactions between two regressive phenotypes. Further, this analysis reveals persistence of background adaptation in Astyanax. As the eye was lost in cave dwelling forms, enhanced pigmentation resulted. Given the extreme cave environment, which is often devoid of nutrition, enhanced pigmentation may impose an energetic cost. Such an energetic cost would be selected against, as a means of energy conservation. Thus, the pleiotropic interaction between vision loss and pigmentation may reveal an additional selective pressure favoring the loss of pigmentation in cave-dwelling animals. PMID- 27363596 TI - Corrigendum: Mutations Closer to the Active Site Improve the Promiscuous Aldolase Activity of 4-Oxalocrotonate Tautomerase More Effectively than Distant Mutations. PMID- 27363597 TI - The social meaning of disability: a reflection on categorisation, stigma and identity. AB - As disability becomes an ever more salient concept in international political and legal discourse, its social meaning must be better understood. Traditionally defined in medical terms and as an individual problem, it has for the last several decades increasingly become a socio-politically defined phenomenon. Disability pride has emerged as a social movement patterned after ethnic minority and sexual orientation movements. The one billion people who count as disabled nevertheless have illnesses and impairments that are largely understood as medical problems. Medicine continues to exert great influence on the social meaning of disability in general and the social valuation of various illnesses and impairments in particular. Whereas specific conditions may be socially valued, the overall category and label of disability connotes marginality and stigma. Under these conditions, disability policy, which ought to be a universal concern, risks being construed as a marginal and special-interest issue rather than a broadly relevant topic; this has potentially negative consequences for the majority of disabled people. PMID- 27363598 TI - The benefits of respectful interactions: fluid alliancing and inter-occupational information sharing in primary care. AB - Though inter-occupational interactions in health care have been the focus of increasing attention, we still know little about how such interactions shape information sharing in clinical settings. This is particularly true in primary care where research on teams and collaboration has been based on individual perceptions of work (using surveys and interviews) rather than observing the interactions that directly mediate the inter-occupational flow of information. To explore how interactions shape information sharing, we conducted a secondary analysis of ethnographic data from 27 primary care practices. Ease of information sharing among nurses and doctors is linked to the degree to which practices feature respectful interactions, with practices in the sample falling into one of three categories (those with low, uneven, and high degrees of respectful interactions). Those practices with the highest degree of respectful interactions demonstrate what we describe as fluid-alliancing: flexible interactions between individuals from different occupational groups in which bidirectional information sharing occurs for the benefit of patients and the efficacy of the practice community. We conclude by arguing that this process unlocks the strengths of all practice members, and that leadership should encourage respectful interactions to augment organisational efficacy and the ability of individual practice members to provide quality patient care. PMID- 27363599 TI - Do overeducated individuals have increased risks of ill health?: a Swedish population-based cohort study. AB - Previous studies indicate that the increasing educational level in many post industrial nations may imply that subgroups of the population work in occupations for which they are overeducated. We aimed to investigate whether overeducation is associated with future self-rated health and psychological distress. The analytical sample consisted of 21,159 participants from the Stockholm Public Health Cohort. Individuals with upper secondary or university education, who in 2006 or 2007 had occupations requiring less education, were considered overeducated. The outcomes were self-rated health (SRH) and psychological distress in 2010. Overeducated women had an increased risk of less than good SRH, compared to university-educated women in matching occupations (adjusted odds ratios (OR): 2.44 confidence intervals (CI): 1.32-4.51 for overeducated women with secondary school education), but not compared to less educated women in the same occupational class (adjusted OR: 0.87 CI:0.32-2.38 for overeducated women with secondary school education). We found no increased risk of less than good SRH for overeducated men, and no association between overeducation and psychological distress for either sex. The results indicate that overeducation is not per se associated with onset of less than good SRH or psychological distress in a short-term perspective, and the findings support education expansion as a means of improving public health. PMID- 27363600 TI - Screening for anxiety and depression in people with psoriasis: a cross-sectional study in a tertiary referral setting. AB - BACKGROUND: National Institute for Health and Care Excellence guidance recommends assessment of psychological and social well-being in people with psoriasis. OBJECTIVES: To screen systematically for depression and anxiety in patients with psoriasis in routine clinical practice and to identify at-risk groups for psychiatric morbidity. METHODS: Consecutive patients attending a single, tertiary centre over a 10-month period were invited to complete the Patient Health Questionnaire Depression Scale (PHQ-9), Generalized Anxiety Disorder Scale (GAD 7) and Dermatology Life Quality Index (DLQI) as part of IMPARTS: Integrating Mental and Physical Healthcare: Research, Training and Services. Information on demographics, treatment and clinical disease severity was collated from electronic patient records. Regression models were used to identify at-risk groups for psychiatric morbidity. RESULTS: Of 607 patients included (56.2% on biologics), 9.9% (95% confidence interval 7.5-12.3%) screened positive for major depressive disorder (MDD) and 13.1% (79/604) (95% confidence interval 10.4-15.8%) for generalized anxiety disorder (GAD; GAD-7 score > 9). Suicidal ideation was reported in 35% of those with MDD; DLQI was < 10 in 38.3% and 45.6% cases of MDD and GAD, respectively. After adjusting for covariates, the risk of MDD or GAD was significantly higher in women and those with severe clinical disease, psoriatic arthritis and previous depression/anxiety. The risk of GAD was significantly increased with Asian ethnicity and use of topical treatments only. CONCLUSIONS: Systematic screening for anxiety and depression identifies clinically important levels of depression and anxiety that may be missed using DLQI data alone. Women and those with severe disease, psoriatic arthritis and/or a prior history of psychiatric morbidity may be at particular risk. PMID- 27363601 TI - Burden of respiratory tract infections at post mortem in Zambian children. AB - BACKGROUND: Autopsy studies are the gold standard for determining cause-of-death and can inform on improved diagnostic strategies and algorithms to improve patient care. We conducted a cross-sectional observational autopsy study to describe the burden of respiratory tract infections in inpatient children who died at the University Teaching Hospital in Lusaka, Zambia. METHODS: Gross pathology was recorded and lung tissue was analysed by histopathology and molecular diagnostics. Recruitment bias was estimated by comparing recruited and non-recruited cases. RESULTS: Of 121 children autopsied, 64 % were male, median age was 19 months (IQR, 12-45 months). HIV status was available for 97 children, of whom 34 % were HIV infected. Lung pathology was observed in 92 % of cases. Bacterial bronchopneumonia was the most common pathology (50 %) undiagnosed ante mortem in 69 % of cases. Other pathologies included interstitial pneumonitis (17 %), tuberculosis (TB; 8 %), cytomegalovirus pneumonia (7 %) and pneumocystis Jirovecii pneumonia (5 %). Comorbidity between lung pathology and other communicable and non-communicable diseases was observed in 80 % of cases. Lung tissue from 70 % of TB cases was positive for Mycobacterium tuberculosis by molecular diagnostic tests. A total of 80 % of TB cases were comorbid with malnutrition and only 10 % of TB cases were on anti-TB therapy when they died. CONCLUSIONS: More proactive testing for bacterial pneumonia and TB in paediatric inpatient settings is needed. PMID- 27363603 TI - Motorized versus manual instrumented spasticity assessment in children with cerebral palsy. AB - AIM: We compared the outcomes of manual and motorized instrumented ankle spasticity assessments in children with cerebral palsy (CP). METHOD: Ten children with spastic CP (three males, seven females; mean age 11y [standard deviation 3y], range 6-14y; Gross Motor Function Classification System levels I-III) were included. During motorized assessments, fast (100 degrees /s) rotations were imposed around the ankle joint by a motor-driven footplate; during manual assessments, rotations of comparable speed were applied by a therapist using a foot orthotic. Angular range of motion, maximum velocity, acceleration, work, and muscle activity (electromyography [EMG]) of the triceps surae and tibialis anterior were compared during passive muscle stretch between motorized and manual assessments. Both movement profiles were also compared to CP gait ankle movement profile. RESULTS: The imposed movement profile differed between methods, with the motorized assessment reaching higher maximum acceleration. Despite equal maximum velocity, the triceps surae were more often activated in motorized assessments, with low agreement of 44% to 72% (kappa<=0) for EMG onset occurrence between methods. The manually applied ankle velocity profile matched more closely with the gait profile. INTERPRETATION: The differences in acceleration possibly account for the different muscle responses, which may suggest acceleration, rather than velocity-dependency of the stretch reflex. Future prototypes of instrumented spasticity assessments should standardize movement profiles, preferably by developing profiles that mimic functional tasks such as walking. PMID- 27363602 TI - Changes in the expression of splicing factor transcripts and variations in alternative splicing are associated with lifespan in mice and humans. AB - Dysregulation of splicing factor expression and altered alternative splicing are associated with aging in humans and other species, and also with replicative senescence in cultured cells. Here, we assess whether expression changes of key splicing regulator genes and consequent effects on alternative splicing are also associated with strain longevity in old and young mice, across 6 different mouse strains with varying lifespan (A/J, NOD.B10Sn-H2(b) /J, PWD.Phj, 129S1/SvlmJ, C57BL/6J and WSB/EiJ). Splicing factor expression and changes to alternative splicing were associated with strain lifespan in spleen and to a lesser extent in muscle. These changes mainly involved hnRNP splicing inhibitor transcripts with most changes more marked in spleens of young animals from long-lived strains. Changes in spleen isoform expression were suggestive of reduced cellular senescence and retained cellular proliferative capacity in long-lived strains. Changes in muscle isoform expression were consistent with reduced pro inflammatory signalling in longer-lived strains. Two splicing regulators, HNRNPA1 and HNRNPA2B1, were also associated with parental longevity in humans, in the InCHIANTI aging study. Splicing factors may represent a driver, mediator or early marker of lifespan in mouse, as expression differences were present in the young animals of long-lived strains. Changes to alternative splicing patterns of key senescence genes in spleen and key remodelling genes in muscle suggest that correct regulation of alternative splicing may enhance lifespan in mice. Expression of some splicing factors in humans was also associated with parental longevity, suggesting that splicing regulation may also influence lifespan in humans. PMID- 27363604 TI - Sedative choice in drug-induced sleep endoscopy: A neuropharmacology-based review. AB - OBJECTIVE: To examine the suitability of commonly used agents for drug-induced sleep endoscopy (DISE) based on agent-specific neuropharmacology. DATA SOURCES: PubMed. REVIEW METHODS: A literature search of the PubMed database was performed on January 1, 2016. A two-layered search strategy was performed to identify relevant pharmacologic agents and articles related to neuropharmacology for these agents. The first search identified relevant pharmacologic agents; the second search examined agents with greater than five results from search 1, along with medical subject headings "respiration," "sleep," "pharmacology," and/or "[respective agent] (e.g., propofol)." Articles not in English were excluded. Bibliographies of pertinent articles were hand-searched for additional articles. RESULTS: Three agents were commonly identified from search 1: propofol, midazolam, and dexmedetomidine with 44, 13, and 6 results, respectively. Of note, 11 results utilized coinduction with midazolam and propofol. Search 2 for propofol, midazolam, and dexmedetomidine retrieved 219, 220, and 26 results, respectively. Eleven results for propofol, 4 for midazolam, and 9 for dexmedetomidine were found to be related to their neuropharmacology. CONCLUSION: The current review demonstrates relatively few investigations seeking to characterize the neuropharmacologic suitability of DISE agents. Compared to propofol and midazolam, dexmedetomidine's mechanism of action appears most likely to induce natural sleep pathways. Further study of its effect on upper airway collapsibility (critical closing pressure) and pharyngeal muscle tone (genioglossus electrode electromyography) are needed. Laryngoscope, 2016 Laryngoscope, 127:273-279, 2017. PMID- 27363605 TI - Synthesis, characterization and evaluation of antibacterial activity of (E)-N' (substituted benzylidene)-2-(2-fluorobenzyl)-5-ethyl-2H-1,2,3-triazole-4 carbohydrazides. AB - Triazoles and their derivatives are important precursors in the pharmacological field due to their broad diversity of medicinal and biological deed. In this article, the exploration is to put an effort to produce some novel biologically active triazole 4-carbohydrazide derivatives. The structures of the newly synthesized compounds were characterized and confirmed by spectral data and were screened for anti-bacterial activity. Compounds 5(d-i), 5l and 5m were observed to possess potent anti-microbial activity. PMID- 27363606 TI - Structural and functional characterization of the microtubule interacting and trafficking domains of two oomycete chitin synthases. AB - Chitin synthases (Chs) are responsible for the synthesis of chitin, a key structural cell wall polysaccharide in many organisms. They are essential for growth in certain oomycete species, some of which are pathogenic to diverse higher organisms. Recently, a microtubule interacting and trafficking (MIT) domain, which is not found in any fungal Chs, has been identified in some oomycete Chs proteins. Based on experimental data relating to the binding specificity of other eukaryotic MIT domains, there was speculation that this domain may be involved in the intracellular trafficking of Chs proteins. However, there is currently no evidence for this or any other function for the MIT domain in these enzymes. To attempt to elucidate their function, MIT domains from two Chs enzymes from the oomycete Saprolegnia monoica were cloned, expressed, and characterized. Both were shown to interact strongly with the plasma membrane component, phosphatidic acid, and to have additional putative interactions with proteins thought to be involved in protein transport and localization. Aiding our understanding of these data, the structure of the first MIT domain from a carbohydrate-active enzyme (MIT1) was solved by NMR, and a model structure of a second MIT domain (MIT2) was built by homology modeling. Our results suggest a potential function for these MIT domains in the intracellular transport and/or regulation of Chs enzymes in the oomycetes. DATABASE: Structural data are available in the Biological Magnetic Resonance Bank (BMRB) database under the accession number 19987 and the PDB database under the accession number 2MPK. PMID- 27363607 TI - Callous-unemotional traits affect adolescents' perception of collaboration. AB - BACKGROUND: How is the perception of collaboration influenced by individual characteristics, in particular high levels of callous-unemotional (CU) traits? CU traits are associated with low empathy and endorsement of negative social goals such as dominance and forced respect. Thus, it is possible that they could relate to difficulties in interpreting that others are collaborating based on a shared goal. METHODS: In the current study, a community sample of 15- to 16-year olds participated in an eye tracking task measuring whether they expect that others engaged in an action sequence are collaborating, depending on the emotion they display toward each other. Positive emotion would indicate that they share a goal, while negative emotion would indicate that they hold individual goals. RESULTS: When the actors showed positive emotion toward each other, expectations of collaboration varied with CU traits. The higher adolescents were on CU traits, the less likely they were to expect collaboration. When the actors showed negative emotion toward each other, CU traits did not influence expectations of collaboration. CONCLUSIONS: The findings suggest that CU traits are associated with difficulty in perceiving positive social interactions, which could further contribute to the behavioral and emotional problems common to those with high CU traits. PMID- 27363608 TI - Determining the Turnover of Glycosphingolipid Species by Stable-Isotope Tracer Lipidomics. AB - In this study, we used water-soluble stable mass isotope precursors to measure the turnover of endogenous ceramide (Cer) and glycosphingolipids (GSLs) in HEp-2 cells. Cells incubated in the presence of [13C-U]glucose showed rapid incorporation of hexose residues with an increased mass of 6Da into GSLs. Different turnover rates of GSL classes and their molecular species were observed. Approximately 30% of the glucosylceramide, 50% of the lactosylceramide, and 50% of the globotriaosylceramide species showed a much slower turnover than the rest. This demonstrates the existence of different lipid pools, where a certain fraction of species survived for a long time in the cells. The species with the shortest N-amidated fatty acyl groups (C16:0 and C18:0) showed a more rapid turnover than those with the longest N-amidated fatty acids (C24:0 and C24:1). Experiments with addition of [13C-U]serine were performed to study de novo synthesis of Cer from serine and palmitoyl-CoA. These experiments revealed that de novo synthesis contributes to a minor extent to the total synthesis of new sphingolipids and showed that there is a more rapid formation of the longest Cer species (C24:0 and C24:1) than of the shortest species (C16:0), that is, the opposite as observed for the GSLs in the experiments with [13C-U]glucose. In conclusion, this FLUX lipidomics experimental approach with the addition of [13C U]glucose to cells allows us to not only study the total turnover but also permit observations of lipid intermediates and metabolic flow of endogenous GSL species at the molecular lipid level. PMID- 27363610 TI - [Benefits of spironolactone as the optimal treatment for drug resistant hypertension. Pathway-2 trial review]. AB - Pathway-2 is the first randomised, double-blind and crossover trial that compares spironolactone as a fourth drug with alfa-blocker, beta-blocker and placebo. This study shows that spironolactone is the drug with more possibilities of success for the management of patients with difficult-to-treat hypertension in patients with a combination of three drugs and poor control. The results validate the widespread treatment with mineralocorticoid receptor antagonists in resistant hypertension. PMID- 27363611 TI - Forced oscillation: A poorly exploited tool for simply assessing respiratory function in children. PMID- 27363609 TI - Noncanonical Myo9b-RhoGAP Accelerates RhoA GTP Hydrolysis by a Dual-Arginine Finger Mechanism. AB - The GTP hydrolysis activities of Rho GTPases are stimulated by GTPase-activating proteins (GAPs), which contain a RhoGAP domain equipped with a characteristic arginine finger and an auxiliary asparagine for catalysis. However, the auxiliary asparagine is missing in the RhoGAP domain of Myo9b (Myo9b-RhoGAP), a unique motorized RhoGAP that specifically targets RhoA for controlling cell motility. Here, we determined the structure of Myo9b-RhoGAP in complex with GDP-bound RhoA and magnesium fluoride. Unexpectedly, Myo9b-RhoGAP contains two arginine fingers at its catalytic site. The first arginine finger resembles the one within the canonical RhoGAP domains and inserts into the nucleotide-binding pocket of RhoA, whereas the second arginine finger anchors the Switch I loop of RhoA and interacts with the nucleotide, stabilizing the transition state of GTP hydrolysis and compensating for the lack of the asparagine. Mutating either of the two arginine fingers impaired the catalytic activity of Myo9b-RhoGAP and affected the Myo9b-mediated cell migration. Our data indicate that Myo9b-RhoGAP accelerates RhoA GTP hydrolysis by a previously unknown dual-arginine-finger mechanism, which may be shared by other noncanonical RhoGAP domains lacking the auxiliary asparagine. PMID- 27363612 TI - [Current controversies regarding power morcellation and future directions]. AB - Modern surgery tends to the improvement of minimally invasive strategies. Laparoscopy, rooted in practices for years, supplanted laparotomy in many directions. Regarding the extraction of large uterus, morcellation is currently the only way to externalize surgical specimens (myomas, uterine), without increasing the skin opening while allowing to reduce postoperative complications compared to laparotomy. However, in 2014, the Food and Drug Administration (FDA) discourages the use of uterine morcellation because of oncological risk. This recommendation has been challenged by a part of the profession. Our review has sought to identify the evidence for and against the use of morcellation. We also tried to quantify surgical risk and the current means of prevention. The incidence of uterine sarcomas is still poorly identified and preoperative diagnostic facilities remain inadequate. The small number of retrospective studies currently available could not enable any recommendation. The evaluation of morcellation devices and the improvement of preoperative diagnosis modalities (imaging, preoperative biopsy) are to continue to minimize the oncological risk. PMID- 27363613 TI - [Breast cancer and Big Data: Evolution or revolution?]. PMID- 27363614 TI - [Screening of aneuploidies in twin pregnancies in 2016: We may miss the boat if we fail to take action]. PMID- 27363615 TI - [Current surgical practice of prophylactic and opportunistic salpingectomy in France]. AB - OBJECTIVES: Since the recent evidence of a tubal origin of most ovarian cancers, opportunistic salpingectomy could be discussed as a prophylactic strategy in the general population and with hereditary predisposition. We aimed to survey French gynecological surgeons about their current surgical practice of prophylactic salpingectomy. METHODS: An anonymous online survey was sent to French obstetrician-gynaecologists and gynecological surgeons. There were 13 questions about their current clinical practice and techniques of salpingectomy during a benign hysterectomy or as a tubal sterilization method, salpingectomy versus salpingo-oophorectomy in the population with genetic risk, salpingectomy in relationship with endometriosis and questions including histopathological considerations. RESULTS: Among the 569 respondents, opportunistic salpingectomy was always performed between 42.48% and 43.44% during laparoscopic, laparoscopic assisted vaginal or laparotomic hysterectomy and only 12.26% in case of vaginal route. In the genetic population, salpingo-oophorectomy was mainly performed. Tubal sterilization was often practiced by the hysteroscopic route. More than 90% of respondents didn't perform salpingectomy in case of endometriosis. There was not any specific tubal histopathological protocol in 71.54% of cases. CONCLUSIONS: Salpingectomy may be a preventing strategy in the low- and high-risk population. The survey's responses show that salpingectomy seems to be a current practice during benign hysterectomy for more than 40% doctors. However, there is not any change with no more salpingectomy in the population with genetic risk, or in case of endometriosis or tubal sterilization. PMID- 27363616 TI - Effects of mix ratio, moisture content and aeration rate on sulfur odor emissions during pig manure composting. AB - Sulfur compounds in swine manure can cause odor emissions during composting if conditions are not conducive to their rapid oxidation and degradation. In this study, the effects of controllable composting process variables on sulfur odor emissions were investigated. These included pig manure to corn stalk mix ratio (0.7:1, 1.5:1 and 2.2:1dw basis), initial moisture content (60%, 65%, 70% and 75%) and aeration rate (1.0, 2.0, 3.0 and 4.0m(3)m(-3)h(-1)). The compounds measured were carbonyl sulfide, carbon disulfide, hydrogen sulfide, methyl mercaptan, ethyl mercaptan, diethyl sulfide, dimethyl sulfide (Me2S) and dimethyl disulfide (Me2SS). The results showed that total sulfur losses ranged from 3.9% to 18.3% after 26days of composting. Me2S and Me2SS were the primary (>59.61%) sulfur compounds released during this period. After turning, emission rates of both Me2S and Me2SS increased. Emissions of the other six sulfur compounds were low and inconsistent during composting. Within the compost, feedstock mix ratio significantly influenced the concentration of Me2SS, while aeration rate significantly affected Me2S concentration (p<0.05). Moisture content did not have a significant effect on the concentrations of either of these two compounds. Concentrations of sulfur odor compounds were the lowest at the highest aeration rate. Therefore, high aeration rates during the thermophilic phase, especially after turning, are recommended to minimize sulfur odors produced during swine manure composting. PMID- 27363617 TI - Characterisation of foot clearance during gait in people with early Parkinson's disease: Deficits associated with a dual task. AB - Tripping is a common cause of falls in older adults and people with Parkinson's disease (PD). Foot clearance during gait may be impaired when distracted by a dual task and thus inform trip risk. This study aimed to evaluate whether foot clearance is impaired in PD and is adversely affected by a dual task. 81 older adults and 76 PD walked at a comfortable pace for two minutes under single and dual task conditions (digit recall). Temporal spatial gait was measured using an instrumented walkway. Heel and toe trajectories were obtained bilaterally using 3 dimensional motion capture. Foot clearance was reduced in PD (p<.001) and under dual task (p<.027). The take-off (toe) gradient was reduced under dual task irrespective of group and the landing (heel) gradient was reduced in PD irrespective of task (p<.001). An increased proportion of unimodal toe distributions were observed for PD, particularly under dual task. Group differences were retained when controlling for step length (landing gradient and peak toe clearance in late swing) and gait velocity (landing gradient). Distinct differences in foot clearance were observed even in the early clinical stages of PD. Dual tasking may increase trip risk due to insufficient toe clearance (early swing) for both older adults and PD. Inadequate heel clearance (late swing) may increase falls risk in PD. Clearance deficits in PD are partially related to a reduced gait velocity and step length which may be targeted in tailored therapies. Further work is necessary to understand the mechanisms underlying this pathology-associated deficit. PMID- 27363618 TI - Postoperative follow-up practice of phyllodes tumour in the UK: Results from a national survey. AB - BACKGROUND: Resected phyllodes tumours (PT) of the breast carry a small but significant risk of recurrence. Nevertheless, there are no national guidelines on the postoperative follow-up of these tumours potentially resulting in a wide variation in practice among breast surgeons in the UK. METHODS: A web-based questionnaire was sent to breast surgeons across the UK to assess individual follow-up practices including availability of local guidelines, methods of follow up and influence of risk factors. RESULTS: Only 38% of 121 responses indicated the availability of local guidelines on PT follow-up. Modal follow-up duration for borderline and malignant disease was 5 years (53.7% and 79.3% of responses respectively), compared to 1 year for benign disease (43%) although 28% of respondents continue to review benign cases for 5 years. Immediate post-operative discharge and self-directed aftercare for benign and borderline cases remains uncommon practice in the UK. Within hospitals represented by more than one respondent in this survey, only around 30% demonstrated consistent practices pertaining to length and frequency of postoperative PT follow-up. Recurrent disease and margin status influenced the follow-up practice of 60% of respondents in our survey. More than 75% indicated that they combine clinical examination with radiological investigations (mammography and/or ultrasound) to follow up PT postoperatively. CONCLUSION: This survey highlights the wide variation in follow up practice for resected PT. This may affect the detection of disease relapse or, conversely, result in wasted clinical resources and unnecessary patient distress. Evidence-based national guidelines are necessary to resolve this issue and inform best follow-up practice. PMID- 27363619 TI - CXCR4 signaling in health and disease. AB - Chemokines and chemokine receptors regulate multiple processes such morphogenesis, angiogenesis and immune responses. Among the chemokine receptors, CXCR4 stands out for its pleiotropic roles as well as for its involvement in several pathological conditions, including immune diseases, viral infections and cancer. For these reasons, CXCR4 represents a crucial target in drug development. In this review, we discuss of CXCR4 receptor properties and signaling in health and diseases, focusing on the WHIM syndrome, an inherited immunodeficiency caused by mutations of the CXCR4 gene. PMID- 27363620 TI - N-Acetyl-l-cysteine exacerbates generation of IL-10 in cells stimulated with endotoxin in vitro and produces antipyresis via IL-10 dependent pathway in vivo. AB - N-Acetyl-l-cysteine (NAC) is a well-known medication, primarily used as a mucolytic agent in pulmonary disease. Recently, we have found that NAC possesses antipyretic properties. The aim of the present study was to investigate the mechanism by which NAC attenuates fever. The concentration of interleukin (IL)-10 and prostaglandin (PG) E2 were measured using ELISA kit in the supernatants aspirated after stimulation of peripheral blood mononuclear cells (PBMCs) with lipopolysaccharide (LPS, 1MUg/mL) and NAC (10mM). The body temperature of the Wistar rats was measured using biotelemetry system. To inhibit endotoxic fever, NAC (200mg/kg; i.p.) was injected into the rats one hour prior to the LPS administration (50MUg/kg; i.p.). The pre-treatment of LPS-stimulated PBMCs with NAC resulted in a significant decrease in PGE2 concentration in comparison to the cells treated with LPS alone (PGE2 level was 386.1+/-61.9pg/mL vs. 2078.9+/ 157.9pg/mL, respectively, p<0.001). Furthermore, in these cells we observed a significant increase in IL-10 level (142.1+/-2.62pg/mL in NAC+LPS stimulated cells vs. 54.4+/-0.6pg/mL in LPS stimulated cells, p<0.001). The injection of anti-IL-10 antibody into the rats abolished antipyretic properties of NAC. Body temperature in animals treated with anti-IL-10+NAC/LPS was 38.28+/-0.12 degrees C vs. 37.73+/-0.06 degrees C in IgG+NAC/LPS rats (p<0.001) and 38.31+/-0.20 degrees C in NaCl/LPS-treated animals (n.s.). Based on these data, we conclude that NAC acts as an antipyretic via IL-10 stimulation. This finding provides a new insight into the immunopharmacology of NAC, and we believe that in a future it will contribute to the new and/or more accurate application of NAC in medicine. PMID- 27363621 TI - Quality of Life in Physical and Psychological Health and Social Environment at Posthospitalization Period in Patients with Stroke. AB - BACKGROUND: Interaction of quality of life (QOL) in physical and psychological health and social environment has not been tested in stroke during a posthospitalization period, and a better understanding of the components of QOL would lead to a more integrated and person-centered approach to health management and outcome optimization. We investigated how QOL emerges from the sequelae of stroke and interacts with each other during the posthospitalization period. METHODS: We performed a cross-sectional study in 53 outpatients of stroke survivors (39 men and 14 women with a mean age of 66 years, 46 infarctions, and 7 hemorrhages). RESULTS: Eight QOL domains of psychological health were scored by interview, and 2 of them ("desire to distend what they can do" or "desire to do rehabilitation") were associated with the improvement of physical health during the posthospitalization period (P < .05 and P = .08, respectively). These patients were characterized by the items like "I need to succeed for health improvement, to go home, to go back to work, and to see grandchildren" as goals to achieve their desire (P < .05). In interaction of QOL in psychological health and social environment, another psychological domain "to gain satisfaction from the experience" was closely related to the presence of hobby or work before stroke attack (P < .05). CONCLUSION: During the posthospitalization period, QOL of psychological health may support that of physical health, being associated with the presence of hobby or work before stroke attack. PMID- 27363622 TI - Sex-Related Differences in the Risk of Hospital-Acquired Sepsis and Pneumonia Post Acute Ischemic Stroke. AB - BACKGROUND AND OBJECTIVE: Infectious complications after ischemic stroke are frequent and lead to neurological deterioration, poor functional outcomes, and higher mortality. Local and systemic inflammatory responses to brain ischemia differ between males and females, but little is known about differences in poststroke susceptibility to infection by sex. The purpose of this study was to compare sex-related differences in the risk of hospital-acquired sepsis and pneumonia after acute ischemic stroke (AIS). MATERIALS AND METHODS: This is a retrospective, secondary analysis of the 2010-2011 California State Inpatient Database. Previously validated International Classification of Disease, Ninth Revision (ICD-9) codes were used to identify adult hospitalizations for AIS. The primary outcome was hospital-acquired sepsis or pneumonia, also identified using ICD-9 codes. Associations between sex and hospital-acquired sepsis or pneumonia were adjusted for baseline characteristics and comorbidities using multivariable logistic regression. RESULTS: There were 91,643 hospitalizations for AIS included in this analysis, of which 1027 had hospital-acquired sepsis and 1225 had hospital-acquired pneumonia. The in-hospital mortality without infection was 4.6%; the presence of hospital-acquired infections was associated with higher mortality for sepsis (32.7%) and pneumonia (21.9%). Female (versus male) sex was associated with lower adjusted odds of hospital-acquired sepsis (odds ratio [OR] .74, 95% confidence interval [CI] .65-.84) and pneumonia (OR .69, 95% CI .62 .78). This difference was similar across age strata. Among hospitalizations with either hospital-acquired sepsis or pneumonia, sex did not influence mortality. CONCLUSIONS: Female sex was associated with a lower risk of hospital-acquired sepsis and pneumonia after AIS. Further investigation is needed to determine the mechanisms underlying this clinical observation. PMID- 27363623 TI - Influence of the Cyclooxygenase-2 Gene -765G/C and -1195G/A Polymorphisms on Development of Ischemic Stroke. AB - BACKGROUND: Many studies have investigated the association between the cyclooxygenase-2 (COX-2) gene polymorphism and ischemic stroke. However, results of these studies still remain controversial. To better explain the association between COX-2 polymorphisms (-765G/C and -1195G/A) and ischemic stroke risk, a meta-analysis was performed. METHODS: Relevant studies were identified from 4 Chinese databases (Chinese Biological Medical Literature database, Chinese National Knowledge Infrastructure database, Chongqing VIP database, and Chinese WANFANG database), PUBMED and EMBASE prior to December 2015. The strength of association between COX-2 polymorphism and ischemic stroke was evaluated by the odds ratio (OR) with 95% confidence interval (CI). Inconsistency index (I(2)) and the Cochran's Q statistic were used to check heterogeneity. Publication bias was evaluated by funnel plots and Egger's regression test. RESULTS: A total of 4086 ischemic stroke cases and 4747 controls were identified. Significant association between COX-2 -765G/C polymorphism and the risk of ischemic stroke was found in Brazilians and the African-Americans. The OR of (CC+GC versus GG) for the Brazilians and African-Americans were (6.328, 95% CI = 2.295-17.448) and (1.644, 95% CI = 1.060-2.551). In addition, the recessive model of the Brazilians gave an OR of 3.621 (95% CI: 1.519-8.630). Furthermore, the (GC versus GG) and the allele model of the African-Americans were (OR: 1.615, 95% CI = 1.015-2.572) and (OR: 1.422, 95% CI = 1.033-1.957). Significant association was also observed for COX-2 -1195G/A polymorphism in the subtypes of small vessel disease (SVD) of ischemic stroke. CONCLUSIONS: Our study suggests that COX-2 -765G/C and -1195G/A polymorphisms may contribute to susceptibility of ischemic stroke, specifically in Brazilians and the African-Americans, and those of SVD. PMID- 27363624 TI - Safe bridging to warfarin in heparin-induced thrombocytopenia. PMID- 27363625 TI - Organelle acidification negatively regulates vacuole membrane fusion in vivo. AB - The V-ATPase is a proton pump consisting of a membrane-integral V0 sector and a peripheral V1 sector, which carries the ATPase activity. In vitro studies of yeast vacuole fusion and evidence from worms, flies, zebrafish and mice suggested that V0 interacts with the SNARE machinery for membrane fusion, that it promotes the induction of hemifusion and that this activity requires physical presence of V0 rather than its proton pump activity. A recent in vivo study in yeast has challenged these interpretations, concluding that fusion required solely lumenal acidification but not the V0 sector itself. Here, we identify the reasons for this discrepancy and reconcile it. We find that acute pharmacological or physiological inhibition of V-ATPase pump activity de-acidifies the vacuole lumen in living yeast cells within minutes. Time-lapse microscopy revealed that de acidification induces vacuole fusion rather than inhibiting it. Cells expressing mutated V0 subunits that maintain vacuolar acidity were blocked in this fusion. Thus, proton pump activity of the V-ATPase negatively regulates vacuole fusion in vivo. Vacuole fusion in vivo does, however, require physical presence of a fusion competent V0 sector. PMID- 27363627 TI - Empathy Predicts an Experimental Pain Reduction During Touch. AB - Previous studies have provided evidence for pain-alleviating effects of segmental tactile stimulation, yet the effect of social touch and its underlying mechanism is still unexplored. Considering that the soma affects the way we think, feel, and interact with others, it has been proposed that touch may communicate emotions, including empathy, interacting with the identity of the toucher. Thus, the goal of the current study was to examine the analgesic effects of social touch, and to test the moderating role of the toucher's empathy in analgesia using an ecological paradigm. Tonic heat stimuli were administered to women. Concurrently, their partners either watched or touched their hands, a stranger touched their hands, or no one interacted with them. The results revealed diminished levels of pain during partners' touch compared with all other control conditions. Furthermore, taking into account the dyadic interaction, only during the touch condition we found 1) a significant relationship between the partners' pain ratings, and 2) a significant negative relationship between the male touchers' empathy and the pain experience of their female partners. The findings highlight the powerful analgesic effect of social touch and suggest that empathy between romantic partners may explain the pain-alleviating effects of social touch. PERSPECTIVE: Pain research mostly concentrates on different factors around a single pain target, without taking into account various social interactions with the observers. Our findings support the idea that pain perception models should be extended, taking into account some psychological characteristics of observers. Our conclusions are on the basis of advanced statistical methods. PMID- 27363626 TI - Pediatric Pain Beliefs Questionnaire: Psychometric Properties of the Short Form. AB - Cognitive appraisals inform and shape individuals' pain experiences. As researchers examine mechanisms of cognitive-behavioral interventions for chronic pain, psychometrically sound measures based in cognitive theory are needed to directly assess pain beliefs. The Pain Beliefs Questionnaire (PBQ), a 32-item self-report measure informed by coping and appraisal theory, was designed to assess children's pain threat appraisals, problem-focused pain coping efficacy, and emotion-focused pain coping efficacy. The present study aimed to: 1) create a short form of the PBQ, and 2) evaluate the psychometric properties of the reduced measure in a large database of pediatric patients with functional abdominal pain (n = 871). Item reduction analyses identified an 18-item short form of the PBQ (PBQ-SF) that exhibited psychometric properties similar to the original measure. All 3 subscales of the PBQ-SF exhibited strong internal consistency (alpha levels ranged from .79 to .80) and adequate test-retest reliability at 2 weeks. Evidence for construct validity was provided by examining patterns of partial correlations for each subscale. The PBQ-SF represents a valid and reliable measure for evaluating children's pain beliefs. Future studies should investigate the treatment sensitivity of the PBQ-SF to evaluate its appropriateness for use in clinical trials. PERSPECTIVE: This article presents the psychometric properties of a reduced 18-item version of a measure used to assess children's pain beliefs in a large sample of children with functional abdominal pain. This measure could help identify processes and individual differences underlying children's responses to psychological treatments for chronic pain. PMID- 27363628 TI - Two Obese Patients with Presumptive Diagnosis of Anaphylactoid Syndrome of Pregnancy Presenting at a Community Hospital. AB - BACKGROUND: Anaphylactoid syndrome of pregnancy (ASP) is a rare but extremely serious complication, with an estimated incidence in North America of 1 in 15 200 deliveries. Despite its rarity, ASP is responsible for approximately 10% of all childbirth-associated deaths in the United States. At present, there is no validated biomarker or specific set of risk factors sufficiently predictive of ASP risk to incorporate into clinical practice. Toward the goal of developing a methodology predictive of an impending ASP event for use by obstetricians, anesthesiologists, and other practitioners participating in infant deliveries, physicians encountering an ASP event have been encouraged to report the occurrence of a case and its biologically plausible risk factors. CASE REPORT: Herein, we report on 2 patients who presented with a presumptive diagnosis of ASP to the delivery unit of a community hospital. Patient One was a 21-year-old, obese (5'11" tall, 250 lbs., BMI 34.9) white female, 1 pregnancy, no live births (G1P0), estimated gestational age (EGA) 40.2 weeks. Patient Two was a 29-year old, obese (5'7" tall, 307 lbs., BMI 48.1) Hispanic female, second pregnancy, with 1 previous live birth via C-section (G2P1-0-0-1). Her pregnancy was at gestational age 38 weeks plus 2 days. CONCLUSIONS: Patient One had 2 possible risk factors: administration of Pitocin to induce labor and post-coital spotting from recent intercourse. Patient Two suffered premature rupture of the placental membranes. Both Patient One and Patient Two had very high body mass indices (BMIs), at the 97th and 99th percentiles, respectively. In the relatively few cases of anaphylactoid syndrome of pregnancy described to date, this is the first report of a possible association with high BMI. PMID- 27363629 TI - A cost and outcome analysis of pediatric single-incision appendectomy. AB - BACKGROUND: For appendicitis, single-incision laparoscopic appendectomy (SIA) has been proposed as an alternative to 3-port appendectomy (3PA). However, there remains controversy regarding outcomes and cost of SIA. We sought to review our experience with these two techniques to identify differences in these factors. MATERIALS AND METHODS: The charts of children (0-17 y) who underwent appendectomy at a tertiary pediatric hospital from 2011-2014 were retrospectively reviewed. Appendectomy was either performed through traditional 3PA or SIA (laparoscopically assisted via externalization through an umbilical incision). Demographic data including age, body mass index, comorbidities, and gender were examined. Information on perforation, operative time and cost, length of stay, and infectious complications for both SIA and 3PA was identified. Data were analyzed using student t tests and chi square analysis. RESULTS: A total of 337 patients underwent appendectomy (141 SIA and 197 3PA), 35.6% of whom (40 SIA, 80 3PA) had perforated appendicitis. For nonperforated appendicitis, SIA had significantly shorter operative times, decreased operative costs, and length of stay. However, these differences were not found for perforated appendicitis. Regardless of appendicitis severity, there was no difference in rates of wound infection, abscess, or readmission between the two techniques. CONCLUSIONS: Our study suggests that SIA is a faster, more cost effective alternative than 3PA for acute appendicitis. SIA did not result in increased infection rates for acute or perforated appendicitis and can be considered an equivalent alternative to 3PA in the surgical management of appendicitis. PMID- 27363630 TI - Borrmann type IV gastric cancer should be classified as pT4b disease. AB - BACKGROUND: The impact of macroscopic pathologic features of primary tumor that could be obtained preoperatively on pT classification has not been reported so far. The aim of this study was to investigate the feasibility of incorporation of Borrmann type IV gastric cancer into the pT classification. MATERIALS AND METHODS: Clinicopathologic and prognostic data of 1622 patients with advanced gastric cancer who underwent radical surgery were retrospectively studied. RESULTS: Of 1622 patients, 135 (8.32%) patients were classified as having Borrmann type IV gastric cancer. We first confirmed that Borrmann type IV gastric cancer was one of the independent prognostic factors for patients with advanced gastric cancer who underwent radical surgery. Interestingly, we found that overall survival of patients with Borrmann type IV gastric cancer could be clearly distinguished by pN classification and pathological TNM stage but not by pT classification. Importantly, further analysis demonstrated that the prognosis of Borrmann type IV gastric cancers was homogeneous with that of pT4b cancers but poorer than pT2, pT3, pT4a cancers. Therefore, we proposed a novel pT classification in which pT4b disease was defined as cancers that were Borrmann type IV or those that had invaded adjacent structures. Two-step multivariate analysis demonstrated that the novel pT classification was more suitable for prognostic assessment than the original classification. CONCLUSIONS: Classifying Borrmann type IV gastric cancer as pT4b disease improves pT classification prediction of prognosis in patients with advanced gastric cancer after radical surgery. PMID- 27363631 TI - Effect of breviscapine against hepatic ischemia reperfusion injury. AB - BACKGROUND: Breviscapine is an active ingredient extracted from traditional Chinese medicine Erigeron breviscapus. The purpose of this study was to investigate the effect of breviscapine injection on hepatic ischemia and/or reperfusion injury. METHODS: Forty rats were randomly divided into five groups (n = 8): Sham group, Ischemia reperfusion 1 (I/R1) + normal saline (NS) group, I/R1 + breviscapine (Bre), I/R2 + NS group, and I/R2 + Bre group. Group1 and group2 represent ischemia time for 10 min and 30 min, respectively. Breviscapine or normal saline was administered to rats (single dose of 10 mg/Kg, intravenously) 30 min before hepatic ischemia. Serum transaminases, histopathologic changes, malondialdehyde (MDA), and superoxide dismutase (SOD) in liver tissues were evaluated. The expression level of mitochondrial fusion 2 (Mfn2) was also investigated. RESULTS: After 24-h reperfusion, based on the histopathologic analysis, compared with NS control group, the liver function was improved in breviscapine group. Liver enzymes aspartate and alanine aminotransferase levels were significantly lower in the I/R + Bre group, when compared with the I/R + NS group. Pretreatment with breviscapine reduced MDA level (P < 0.05) and increased SOD activity significantly in I/R + Bre compared with I/R + NS group. Western blot and RT-q polymerase chain reaction showed that Mfn2 was significantly downregulated in breviscapine preconditioning group as compared to normal saline control group. CONCLUSIONS: Breviscapine preconditioning attenuates liver ischemia reperfusion injury via inhibiting liver oxidative stress reaction. The protective mechanism probably inhibits Mfn2 protein and mRNA expression. PMID- 27363632 TI - Differentiation of benign and malignant hilar bile duct stenosis. AB - BACKGROUND: Failure to differentiate benign and malignant hilar bile duct stenosis may lead to inappropriate treatment. We retrospectively analyzed the methods for differentiation. MATERIALS AND METHODS: A total of 53 patients with hilar bile duct stenosis were included, comprising 41 malignant cases (hilar cholangiocarcinoma) and 12 benign cases (six primary sclerosing cholangitis and six IgG4-associated sclerosing cholangitis). Data of clinical histories, laboratory tests, imaging studies, and liver pathologies were collected, and comparison was made between benign and malignant groups. RESULTS: Compared with malignant group, patients in the benign group were more likely to have multiorgan involvement of clinical histories (P < 0.001). There was no difference on bilirubin, liver enzyme, and serum tumor marker between the two groups, whereas serum IgG4 levels were higher in the benign group (P = 0.003). Patients in the benign group were more likely to have pancreatic changes (P < 0.001) and multiple segmental bile duct stenosis (P < 0.001) on imaging. Compared with the malignant group, patients in the benign group were more likely to show severe periportal inflammation in noninvolved liver (P < 0.001), fibrosis around intrahepatic bile duct (P < 0.001), and more IgG4-positive plasma cells (P < 0.001) on liver pathology. CONCLUSIONS: Benign lesion should be considered for patients with history of multiorgan involvement, pancreas changes, or multiple-segmental bile duct stenosis on imaging. Liver biopsy could be helpful for differential diagnosis before surgery. PMID- 27363633 TI - Obesity and single-incision laparoscopic appendectomy in children. AB - BACKGROUND: Single-incision laparoscopic appendectomy (SILA) has emerged as a less-invasive alternative to conventional laparoscopy. The purpose of this study was to assess the impact of body habitus on outcomes after SILA in the pediatric population. METHODS: A retrospective review of 413 patients who underwent SILA from 2012 to 2015 was performed. Body mass index (BMI) was calculated, and the BMI percentile was obtained per Center for Disease Control guidelines. Standard definitions for overweight (BMI 85th-94th percentile) and obese (BMI > 95th percentile) were used. General demographic and outcome data were analyzed. RESULTS: SILA was performed in 413 patients during the study period, of which 66.3% were normal weight, 16% were overweight, and 17.7% were obese. There were no significant differences in age at presentation, time to diagnosis, or intraoperative classification of appendicitis. There were no significant differences in operative time (27.0 +/- 9.1 versus 27 +/- 9.8 versus 28.4 +/- 9.4 min, P = 0.514), postoperative length of stay (0.97 +/- 1.65 versus 1.53 +/- 4.15 versus 1.14 +/- 2.27 d, P = 0.214), 30-d surgical site infections (6.9% versus 12.1% versus 8.2%, P = 0.377), emergency department visits (8.4% versus 10.6% versus 11%, P = 0.726), or readmissions (4.7% versus 4.1% versus 4.5%, P = 0.967) among normal, overweight, and obese groups. CONCLUSIONS: Our results indicate that obesity does not significantly impact outcomes after SILA. SILA can be performed in overweight and obese children with no significant difference in operative time, length of stay, or incidence of surgical site infection. SILA should continue to be offered to overweight and obese children. PMID- 27363634 TI - Implementation of national practice guidelines to reduce waste and optimize patient value. AB - BACKGROUND: The financial health care crisis has provided the platform to drive operational improvements at US health care facilities. This has led to adoption of lean operation principles by many health care organizations as a means of eliminating waste and improving operational efficiencies and overall value to patients. We believe that standardized implementation of national practice guidelines can provide the framework to help to reduce financial waste. MATERIALS AND METHODS: We analyzed our institutional preoperative electrocardiogram (ECG) ordering practices for patients undergoing elective surgery at our institution from February-March, 2012 to identify utilization and review compliance with American Heart Association guidelines. We then implemented an ECG ordering algorithm based on these guidelines and studied changes in ordering patterns, associated cost savings and hospital billing for the same period in 2013. RESULTS: From February-March 2012, 677 noncardiac surgical procedures were performed at our institution, and 312 (46.1%) had a preoperative ECG. After implementation of our evidence-based ECG ordering algorithm for the same period in 2013, 707 noncardiac surgical cases were performed, and 120 (16.9%) had a preoperative ECG. Preoperative ECG utilization dropped 63% with an annual institutional cost savings of $72,906 and $291,618 in total annual health care savings. Based on our data, US-wide implementation of our evidence-based ECG ordering algorithm could save the US health care system >$1,868,800,000 per year. CONCLUSIONS: Here, we demonstrate that standardized application of a national practice guideline can be used to eliminate nearly $2 billion per year in waste from the US health care system. PMID- 27363635 TI - Risk factors for survival and recurrence after lung metastasectomy. AB - BACKGROUND: Colorectal cancer (CRC) is the third most diagnosed cancer worldwide, with up to 25% of patients who will develop metastases. Pulmonary metastases (PMs) resection for CRC might improve long-term survival, but the selection criteria for patients who would benefit remain unclear. The aim of this study was to identify preoperative predictive factors in patients eligible for this surgical strategy. MATERIALS AND METHODS: We retrospectively reviewed data of patients from five thoracic surgery departments who underwent PM resection for CRC with intent to cure between 2005 and 2010. Univariate and multivariate analyses were performed to identify predictive factors influencing long-term survival and recurrence after pulmonary resection. RESULTS: Three hundred fifty four patients were eligible. Forty-eight patients had pulmonary recurrence (13.5%). Thirty-day postoperative mortality was 0.3% (n = 1). Five- and 8-y overall survival (OS) were 64.3 +/- 3.99% and 60.72 +/- 4.5%, respectively. In univariate analysis, 5-y OS was significantly associated with an American Society of Anesthesiologists score of 1 (P = 0.02), a low number of PM (P = 0.001), and single wedge resection (P = 0.00001). In multivariate analysis, an American Society of Anesthesiologists score of 3 or higher (P = 0.05), two or more PMs (P = 0.034) and pneumonectomy (P = 0.021) were significant predictors of a poor outcome. In univariate analysis, 5-y cumulative recurrence was significantly associated with the absence of mediastinal lymph node dissection (P = 0.01). CONCLUSIONS: Given its high 5-y OS with low postoperative morbidity, thus allowing repeat surgical management, resection of PM could be performed. Resection of PM could improve long-term survival. PMID- 27363636 TI - Ergonomic analysis of primary and assistant surgical roles. AB - BACKGROUND: Laparoscopic surgery is associated with a high degree of ergonomic stress. However, the stress associated with surgical assisting is not known. In this study, we compare the ergonomic stress associated with primary and assistant surgical roles during laparoscopic surgery. We hypothesize that higher ergonomic stress will be detected in the primary operating surgeon when compared with the surgical assistant. METHODS: One right-hand dominant attending surgeon performed 698 min of laparoscopic surgery over 13 procedures (222 min primary and 476 min assisting), whereas electromyography data were collected from bilateral biceps, triceps, deltoids, and trapezius muscles. Data were analyzed in 1-min segments. Average muscle activation as quantified by maximal voluntary contraction (%MVC) was calculated for each muscle group during primary surgery and assisting. We compared mean %MVC values with unpaired t-tests. RESULTS: Activation of right (R) biceps and triceps muscle groups is significantly elevated while operating when compared with assisting (R biceps primary: 5.47 +/- 0.21 %MVC, assistant: 3.93 +/ 0.11, P < 0.001; R triceps primary: 6.53 +/- 0.33 %MVC, assistant: 5.48 +/- 0.18, P = 0.002). Mean activation of the left trapezius muscle group is elevated during assisting (primary: 4.33 +/- 0.26 %MVC, assistant: 5.70 +/- 0.40, P = 0.024). No significance difference was noted in the other muscle groups (R deltoid, R trapezius, left [L] biceps, L triceps, and L deltoid). CONCLUSIONS: We used surface electromyography to quantify ergonomic differences between operating and assisting. Surgical assisting was associated with similar and occasionally higher levels of muscle activation compared with primary operating. These findings suggest that surgical assistants face significant ergonomic stress, just as operating surgeons do. Steps must be taken to recognize and mitigate this stress in both operating surgeons and assistants. PMID- 27363637 TI - Morphine and ketamine inhibit immune function of gastric cancer patients by increasing percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells in vitro. AB - BACKGROUND: There is conflicting evidence regarding effects of anesthetic and analgesic drugs on immune function of cancer patients. This study was designed to observe changes of T cell subpopulations in the gastric cancer (GC) patients and to assess effects of morphine and ketamine on the CD4(+) T cells, CD8(+) T cells, and regulatory T cells (Tregs) populations obtained from the GC patients in vitro. METHODS: The peripheral blood samples from 20 GC patients and 20 healthy volunteers were obtained. The peripheral blood mononuclear cells were isolated and incubated in a solution containing phorbol-myristate-acetate and ionomycin (2 MUL/mL) in the presence or absence of morphine (50 ng/mL) or different concentration ketamine (25, 50, and 100 MUM). The CD4(+) T cells, CD8(+) T cells, and Tregs were determined using the flow cytometric assay. RESULTS: The percentages of CD8(+) T cells were significantly decreased, but the ratio of CD4(+)/CD8(+) T cells and Tregs populations was significantly increased in the GC control group compared with the normal control group (P < 0.05). The ratio of CD4(+)/CD8(+) T cells was significantly increased in the groups M and K3 compared with the control group (P < 0.05) but was significantly decreased in the group K1 compared with the group K3. The percentage of Tregs was significantly increased in the groups M, K1, K2, and K3 compared with the control group. With the increased concentrations, ketamine increased the number of Tregs. CONCLUSIONS: GC shifts the balance of CD4(+)/CD8(+) T cells toward CD4(+) T cells and increases the Tregs populations by inducing immune responses. Morphine increases the ratio of CD4(+)/CD8(+) T cells and Tregs populations. Ketamine affects the ratio of CD4(+)/CD8(+) T cells and Tregs populations in a dose-dependent model. PMID- 27363638 TI - Cost and radiation exposure in the workup of febrile pediatric urinary tract infections. AB - BACKGROUND: Technetium-99m dimercaptosuccinic acid (DMSA) scans are often used in the evaluation of pediatric patients with febrile urinary tract infections (UTIs). Given the prevalence of febrile UTIs, we sought to quantify the cost, radiation exposure, and clinical utility of DMSA scans when compared with dedicated pediatric renal ultrasounds (RUSs). MATERIALS AND METHODS: An institutional review board approved retrospective study of children under the age of 18 years evaluated at our institution for febrile UTIs between the years 2004 2013 was conducted. The patients had to meet all of the following inclusion criteria: a diagnosis of vesicoureteral reflux, a fever >38 degrees C, a positive urine culture, and evaluation with a DMSA scan and RUS. A chart review was used to construct a cost analysis of technical and professional fees, radiographic results, and radiation dose equivalents. RESULTS: Overall, 104 children met the inclusion criteria. A total of 122 RUS and 135 DMSA scans were performed. The technical costs of a DMSA scan incurred a 35% cost premium as compared to an RUS. The average effective radiation dose of a single DMSA scan was 2.84 mSv. New radiographic findings were only identified on 7% of those patients who underwent greater than 1 DMSA scan. CONCLUSIONS: The utility of the unique information acquired from a DMSA scan as compared to a RUS in the evaluation of febrile UTI must be evaluated on an individual case-by-case basis given the increased direct costs and radiation exposure to the patient. PMID- 27363639 TI - Humanitarian skill set acquisition trends among graduating US surgical residents, 2004-2014. AB - BACKGROUND: Although interest in practicing surgery in resource-constrained settings is on the rise among graduating US surgical residents, there is ongoing debate about an optimal humanitarian skill set for surgeons who chose to work in such settings. In addition, increased emphasis on general surgery case exposure at the cost of specialty surgery case exposure has been documented and may have a negative impact on the breadth of resident training. Review of general surgery resident case logs to gauge experience in specialty surgery may provide insight into residents' readiness for work in resource-limited settings. METHODS: We compared Accreditation Council for Graduate Medical Education general surgery resident case logs from 2004 to 2014 for operations thought to be essential for working in resource-constrained settings. These operations were chosen from published literature on this topic and authors' personal experience. Case numbers for specialty operations were compared by unpaired t-test analysis between the two periods. RESULTS: Case averages in pediatric, genitourinary, and gynecologic surgery decreased significantly from 2004 to 2014 (range, 27%-46%). Orthopedic surgery case averages were unchanged, and plastic and general abdominal surgery case averages increased (range, 47%-50%). CONCLUSIONS: Case mix among graduating US surgical residents has narrowed over the past 10 y. Resident experience in a variety of specialty fields, thought to be essential in resource-constrained settings, decreased markedly over the study period. Residents who intend to work in resource-constrained settings may need to craft individualized residency experiences or pursue postgraduate training in specialty surgery courses to best prepare for such work. PMID- 27363640 TI - Estrogen attenuates renal IRI through PPAR-gamma agonism in rats. AB - BACKGROUND: Estrogen is reported to be renoprotective agent in various preclinical studies, attributing to its antioxidant and anti-inflammatory potential. The aim of present study was to investigate the involvement of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in estrogen mediated protection against renal ischemia reperfusion injury (IRI) in rats. MATERIALS AND METHODS: The renal damage induced by IRI (40-min ischemia and 24-h reperfusion) was assessed by measuring serum creatinine, creatinine clearance, blood urea nitrogen, serum uric acid, electrolytes, and microproteinuria in rats. The myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels were measured to assess oxidative stress in renal tissues. Hematoxylin-eosin and periodic acid schiff staining of renal tissues were done to demonstrate histopathologic changes. Estrogen (0.2, 0.5, and 1.0 mg/kg, i.p.) was administered 1 h before subjecting rats to renal IRI. Separately, bisphenol A diglycyl ether (BADGE, 30 mg/kg, i.p.), a PPAR-gamma receptor antagonist, was given before estrogen administration followed by IRI in rats. RESULTS: The ischemia reperfusion demonstrated renal damage in rats with significant changes in serum and urinary parameters, enhanced oxidative stress, and histopathologic changes in renal tissues. Estrogen administration demonstrated marked renoprotection that was attenuated by BADGE pretreatment in rats. CONCLUSIONS: It is concluded that PPAR-gamma agonism serves as one of the mechanisms in estrogen-mediated renoprotection. PMID- 27363641 TI - Rutin attenuates neuroinflammation in spinal cord injury rats. AB - BACKGROUND: Neuroinflammatory responses involve the activation of the interleukin (IL) -1beta and IL-18. Processing and activation of the pro-inflammatory IL require NLRP3 inflammasome activation. Rutin can protect spinal cord against damage, but the potential mechanisms underlying remain unknown. Here, we investigated the molecular mechanisms of rutin-mediated neuroprotection in a rat model of spinal cord injury (SCI). MATERIALS AND METHODS: One hundred twenty female Sprague-Dawley rats were randomly assigned to four groups: sham group, SCI group, SCI + Rutin50 group, and the SCI + Rutin100 group. The influences of rutin on inflammatory marker levels, histologic alterations, and locomotion scale were analyzed. RESULTS: SCI significantly increased the expression of the NLRP3, ASC, IL-1beta, IL-18, and tumor necrosis factor-alpha. Rutin significantly reduced the levels of reactive oxygen species, malondialdehyde, NLRP3, ASC, caspase-1, IL 1beta, IL-18, and tumor necrosis factor-alpha. Furthermore, rutin administration significantly attenuated histologic alteration and improved locomotion recovery. CONCLUSIONS: Our data provide clear evidence that rutin attenuates tissue damage and improves locomotion recovery, and the mechanism may be related to the alleviation of inflammation and oxidative stress. PMID- 27363642 TI - Variation in intensive care unit utilization and mortality after blunt splenic injury. AB - BACKGROUND: Although trauma patients are frequently cared for in the intensive care unit (ICU), admission triage criteria are unclear and may vary among providers and institutions. The benefits of close monitoring must be weighed against the economic and opportunity costs of an ICU admission. MATERIALS AND METHODS: We conducted a retrospective cohort study of patients treated for blunt splenic injuries from 2011-2014 at 30 level I and II Pennsylvania trauma centers. We used multivariable logistic regression to assess the relationship between ICU admission and mortality, adjusting for patient characteristics, injury characteristics, and physiology. We calculated center-level observed-to-expected ratios for ICU utilization and mortality and evaluated correlations with Spearman's rho. We compared the proportion of patients receiving critical care procedures, such as mechanical ventilation or central line placement between high and low-ICU-utilization centers. RESULTS: Of 2587 patients with blunt splenic injuries, 63.9% (1654) were admitted to the ICU. Median injury severity score was 17 overall, 13 for non-ICU patients and 17 for ICU patients (P < 0.001). In multivariable logistic regression, ICU admission was not significantly associated with mortality. Center-level risk-adjusted ICU admission rates ranged from 17.9% 87.3%. Risk-adjusted mortality rates ranged from 1.2%-9.6%. There was no correlation between observed-to-expected ratios for ICU utilization and mortality (Spearman's rho = -0.2595, P = 0.2103). Proportionately fewer ICU patients received critical care procedures at high-utilization centers than at low utilization centers. CONCLUSIONS: Risk-adjusted ICU utilization rates for splenic trauma varied widely among trauma centers, with no clear relationship to mortality. Standardizing ICU admission criteria could improve resource utilization without increasing mortality. PMID- 27363644 TI - Equal distribution of mesenchymal stem cells after hepatic ischemia-reperfusion injury. AB - BACKGROUND: Liver ischemia-reperfusion (I/R) injury is one of the major causes of hepatocellular injury-related mortality and morbidity after liver transplantation. Mesenchymal stem cells (MSCs) have been shown to reduce liver I/R injury and improve regeneration. The purpose of the present study was to investigate the difference in the distribution of systemically delivered MSCs in the recipient's liver between the ischemic injury area and nonischemic area. MATERIAL AND METHODS: Fishers' rats (7-8 week of age) were used as donors of MSCs and recipients. Bone marrow-derived MSCs were isolated from the donor's femur. Before systemic administration, MSCs were labeled with the fluorescent dye PKH26. The rats were divided into four groups: (1) I/R injury + MSC group, (2) MSC only, without I/R injury, (3) I/R injury + saline group, and (4) the Sham group. I/R injury was performed by clamping the inflow vascular structures of the left and middle lobes of the recipient's liver for 60 min. The right lobe was considered as a nonischemic part. Subsequently, 1.5 * 10(6) of MSCs or saline (NaCl, 0.9%) was administrated via the rat's tail vein. Thereafter, the rats were killed after days one, three, or seven for the analyses. RESULTS: A fluorescent microscopy assay for labeled MSCs showed positive cells in both ischemic and nonischemic parts of the recipient's liver. The number of cells was significantly higher in the I/R injury + MSC group compared with the only MSC, without I/R injury group. Immunohistochemical staining showed that there was no significant difference in the proliferation of Ki-67-positive cells between the I/R + MSCs and I/R + saline groups. In addition, the serum transaminase levels were not different between the I/R + MSCs and I/R + saline groups. CONCLUSIONS: After partial liver I/R injury, transplanted MSCs migrate equally to the ischemic and nonischemic parts of the recipient's liver. Considering the unique ability of the liver to regenerate, both parts of the liver presumably receive signals for regeneration. PMID- 27363643 TI - Gastroprotective effects of sulforaphane and thymoquinone against acetylsalicylic acid-induced gastric ulcer in rats. AB - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) commonly cause gastric ulcers (GUs). We investigated the effects of sulforaphane (SF) and thymoquinone (TQ) in rats with acetylsalicylic acid (ASA)-induced GUs. MATERIALS AND METHODS: Thirty-five male Wistar-Albino rats were divided into five groups: control; ASA; ASA with vehicle; ASA + SF; and ASA + TQ. Compounds were administered by oral gavage before GU induction. GUs were induced by intragastric administration of ASA. Four hours after GU induction, rats were killed and stomachs excised. Total oxidant status, total antioxidant status, total thiol, nitric oxide, asymmetric dimethylarginine, tumor necrosis factor-alpha levels, superoxide dismutase activity, and glutathione peroxidase activity in tissue were measured. Messenger RNA expression of dimethylarginine dimethylaminohydrolases, heme oxygenase-1 (HO 1), nuclear factor erythroid 2-related factor 2, and nuclear factor kappa-light chain-enhancer of activated B cells were analyzed. Renal tissues were evaluated by histopathologic and immunohistochemical means. RESULTS: SF and TQ reduced GU indices, apoptosis, total oxidant status, asymmetric dimethylarginine, and tumor necrosis factor-alpha levels, nuclear factor kappa-light-chain-enhancer of activated B cells, and inducible nitric oxide synthase expressions (P < 0.001, P = 0.001). Both examined compounds increased superoxide dismutase activity, glutathione peroxidase activity, total antioxidant status, total thiol, nitric oxide levels, endothelial nitric oxide synthase, dimethylarginine dimethylaminohydrolases, HO-1, nuclear factor erythroid 2-related factor 2, and HO-1 expressions (P < 0.001). CONCLUSIONS: These results suggest that pretreatment with SF or TQ can reduce ASA-induced GUs via anti-inflammatory, antioxidant, and antiapoptotic effects. These compounds may be useful therapeutic strategies to prevent the gastrointestinal adverse effects that limit nonsteroidal anti-inflammatory drugs use. PMID- 27363645 TI - Variation in crystalloid administration: an analysis of 6248 patients undergoing major elective surgery. AB - BACKGROUND: Large variations exist regarding the type and volume of fluid to be administered to patients. This study aimed to quantitate variations in the administration of crystalloid fluids at the level of the patient, provider, and procedure at a large, tertiary care center. METHOD: Patients who underwent major cardiac, thoracic, or abdominal procedures between 2011 and 2014 were identified. Variations in crystalloid administration were compared by procedure and provider using a coefficient of variation (CV). Multivariable hierarchical linear modeling was performed to identify factors predictive of fluid administration and quantitate variation at the level of the patient and provider. RESULTS: Among 6248 patients who met inclusion criteria, the average crystalloid volume was 25.8 mL kg(-1) m(2) h(-1), corresponding to a CV of 55%. Patients who underwent pancreatectomy received the highest corrected crystalloid volume (32.7 mL kg(-1) m(2) h(-1)), whereas those who underwent coronary artery bypass grafting received the lowest corrected crystalloid volume (14.7 mL kg(-1) m(2) h(-1)). Variations in fluid practices were noted between providers (corrected CV; 14.7%-97.1%) and within the practices of the same provider (corrected CV range; 24.1%-87.9%). On multivariable analysis, age and changes in hemoglobin concentration were associated with a higher crystalloid volume (both P < 0.05). Although over 90% of the variation was attributed to patient-level factors, approximately 10% was due to factors at level of the provider (surgeon: 5.8% versus anesthesiologist: 3.4%). CONCLUSIONS: Wide variations were noted in crystalloid administration between procedures, providers, and within providers. Evidence-based practices and goal-directed therapies should be incorporated to avoid unwanted variations. PMID- 27363646 TI - Patient reported outcome measurements in the diagnosis of incisional hernia: PROMIS questionnaire, a pilot study. AB - BACKGROUND: Incisional hernia (IH) is the most frequent complication after abdominal surgery. Long-term follow-up is crucial. Patient-reported outcome measurements (PROMs) are able to monitor patients' disease progression after treatment. Until now, there are no PROMs that assess patients after abdominal surgery or that detects patients with IH. We aimed to develop a reliable questionnaire to assist in diagnosing IH, called the "PROMIS questionnaire": Patient-Reported Outcome Measurements in the Diagnosis of Incisional Hernias. In this pilot study, the reliability of this questionnaire is being determined. METHODS: Patients diagnosed with IH between 2013 and 2014 were included. A questionnaire with seven questions was developed. Patients were asked whether they thought they had IH, whether they felt any pain at the site of the scar, and whether they saw or felt a lump or a bulge. Furthermore, smoking history and patients' weight and height were taken into account. Patients were approached three times by telephone, with an interval of 1 week. Test-retest reliability, internal consistency, and sensitivity were measured. RESULTS: Forty-three patients were included. Test-retest reliability was 1.0, and internal consistency was 0.56. The question regarding patients' pain was least consistent with other questions. The overall sensitivity of the questionnaire was 95%. CONCLUSIONS: The PROMIS questionnaire is a highly reliable questionnaire, but the internal consistency is modest. The clinical relevancy of pain in IH patients is essential. Therefore, this question will be kept in the current PROMIS questionnaire. It needs further validation in a prospective cohort study, to use it as a diagnostic tool in the future to detect IH. PMID- 27363647 TI - N-acetylcysteine amid reduces pancreatic damage in a rat model of acute necrotizing pancreatitis. AB - BACKGROUND: Inflammatory explosion and oxidative stress are important mechanisms of injury in acute necrotizing pancreatitis (ANP). This study investigated the effects of N-acetylcysteine amid (NACA), a novel cell-permeant antioxidant with anti-inflammatory activity, on experimental ANP in rats. MATERIALS AND METHODS: Fifty-two adult male Sprague-Dawley rats were used, and ANP was induced by cerulein. The animals were divided into four groups which were sham + saline, sham + NACA, ANP + saline, and ANP + NACA. NACA (2.2 mg/kg, i.p) was administered for 6 h, after the induction of ANP. The extent of acinar cell injury, mortality, systemic cardiorespiratory variables, functional capillary density, renal/hepatic functions, and changes in some enzyme markers for pancreas and lung tissues were investigated. RESULTS: Induction of ANP increased mortality from 0% in the sham group to 43.75% in the ANP + saline group (P < 0.05), and administration of NACA significantly reduced mortality to 12.5% (P < 0.05). Induction of ANP also caused increases in pancreatic necrosis, serum amylase, alanine aminotransferase (ALT), interleukin-6, LDH in bronchoalveolar lavage fluid, serum urea, tissue myeloperoxidase in pancreas and lung tissues and malondialdehyde. There was less pronounced increase in these parameters in NACA treated group. Compared with ANP group, ANP + NACA group had lower levels of pancreatic necrosis (0.5 +/- 0.2 versus 1.45 +/- 0.2, P < 0.05) and inflammation (0.6 +/- 0.2 versus 1.29 +/- 00.3, P < 0.05) scores. CONCLUSIONS: Administration of NACA significantly decreased the ANP-induced mortality and also provided significant improvements in hemodynamic changes. The obtained positive effects of NACA on the course of pancreatitis indicates its potential usefulness in the management of ANP. PMID- 27363648 TI - Outpatient air leak management after lobectomy: a CMS cost analysis. AB - BACKGROUND: Air leaks after lobectomy are associated with increased length of stay (LOS) and protracted resource utilization. Portable drainage systems (PDS) allow for outpatient management of air leaks in patients otherwise meeting discharge criteria. We evaluated the safety and cost efficiency of a protocol for outpatient management of air leaks with a PDS. METHODS: We retrospectively assessed patients who underwent lobectomy for non-small-cell lung cancer at our institution between 2004 and 2014. All patients discharged with a PDS for air leak were included in the analysis. The study group was compared to an internally matched cohort of patients undergoing lobectomy for non-small-cell lung cancer managed without the need for outpatient PDS. Study end points included resource utilization, postoperative complications, and readmission. RESULTS: A total of 739 lobectomies were performed during the study period, 73 (10%) patients with air leaks were discharged with a PDS after fulfilling postoperative milestones. Shorter LOS was observed in the study group (3.88 +/- 2.4 versus 5.68 +/- 5.7 d, P = 0.014) without significant differences in 30-d readmission (11.7% versus 9.0%, P = 0.615). PDS-related complications occurred in 6.8% of study patients (5/73), and 2.7% (2/73) required overnight readmission. PDSs were used for 8.30 +/- 4.5 outpatient days. A CMS-based cost analysis predicted an overall savings of $686.72/patient (4.9% of Medicare reimbursement for a major thoracic procedure), associated with significantly fewer hospital days and resources used. CONCLUSIONS: In patients otherwise meeting discharge criteria, outpatient management of air leaks is safe and effective. This strategy is associated with improved efficiency of postoperative care and a modest reduction in hospital costs. This model may be applicable to other thoracic procedures associated with protracted LOS. PMID- 27363649 TI - Low vertebral ano-rectal cardiac tracheo-esophageal renal limb screening rates in children with anorectal malformations. AB - BACKGROUND: The aim of this study was to establish the rate of screening for associated cardiac, vertebral, spinal cord, urologic, and limb anomalies vertebral ano-rectal cardiac tracheo-esophageal renal limb (VACTERL) in children with anorectal malformation (ARM). METHODS: We performed a retrospective cohort study using the Medicaid Analytic eXtract database which contains enrollment and utilization claims and demographic information from all Medicaid enrollees. Patients born between January 2005 and December 2008 with International Classification of Diseases, Ninth Revision codes for a diagnosis of ARM within 30 days of life, an ARM procedure code during the first year of life, and a minimum of 12 months of continuous enrollment were included. VACTERL screening was determined using International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes for diagnostic tests used to detect these anomalies. RESULTS: A total of 406 patients were identified (231 males). Evaluation of the spinal vertebrae was performed in 94% of patients (381 of 406). Spinal cord evaluation was performed in 57% (231 of 406): 52% (121 of 231) received spinal ultrasound (US), 24% (56 of 231) received spinal magnetic resonance imaging, and 23% (54 of 231) received both. Sacral radiographs were performed in 8% (32 of 406) and 77% (313 of 406) underwent an echocardiogram. Genitourinary evaluation was performed in 84% (341 of 406): 67% (229 of 341) received renal US, 8% (27 of 341) received abdominal US, and 25% (85 of 341) received both. Limb evaluation was recorded in 19% (76 of 406). Multiple screening including an echocardiogram, spinal radiograph, spinal cord evaluation, and renal evaluation was performed in 45% (181 of 406); 2% (7 of 406) did not receive any screening tests. CONCLUSIONS: Low VACTERL screening in children with ARM suggests that associated anomalies may be undiagnosed which may lead to increased long-term morbidity. PMID- 27363650 TI - Immunohistochemistry as a reliable method for detection of BRAF-V600E mutation in melanoma: a systematic review and meta-analysis of current published literature. AB - BACKGROUND: The BRAF-V600E mutation is associated with tumor aggressiveness and poor prognosis in melanoma patients. Identification of this mutation is clinically important as we now have Food and Drug Administration-approved targeted therapies, such as BRAF and MEK inhibitors, which have been shown to retard disease progression in these patients. Detection of BRAF-V600E by genetic analysis using polymerase chain reaction is the gold standard method for melanoma cases. However, immunohistochemistry (IHC) using a VE1 antibody is rapidly emerging as a trustworthy method for the determination of mutation status in patients' specimens. Our objective in this study was to assess the reliability of IHC compared with genetic methods for successful identification of BRAF-V600E mutation in melanoma tissue specimens. METHODS: A literature search of PubMed, Web of Science, and Embase was performed for studies comparing IHC with genetic analysis for the detection of BRAF in melanoma patients published through May 28, 2015. Pooled sensitivity, specificity, diagnostic odds ratio, positive, and negative likelihood ratios were calculated using a bivariate model. Logit estimates of sensitivity and specificity with their respective variances were used to plot a hierarchical receiver operating characteristic curve and area under the curve. Heterogeneity was assessed using the Q- and I-squared statistics. RESULTS: An initial literature search resulted in 287 articles. After two independent reviews and consensus-based discussion to resolve disparities, 21 studies involving a total of 1687 cases met the eligibility criteria and were included in the analysis. The pooled sensitivity of IHC for BRAF-V600E detection was 0.96; 95% confidence interval (CI, 0.94-0.98), specificity 1.00; 95% CI (0.97 1.00), positive likelihood ratio 194.2; 95% CI (37.6-1003.3), negative likelihood ratio 0.04; 95% CI (0.02-0.07), and diagnostic odds ratio 5503 (1199-25,263), as compared with genetic analysis. A high heterogeneity was observed between these studies (Q value of 40.17 & I(2) = 95%; 95% CI (91-99, P < 0.001) which may be explained by studies using different cutoff values for labeling IHC as positive. High accuracy of IHC was depicted by area under the curve in the receiver operating characteristic curve which was 0.99; 95 % CI (0.98-1.00). CONCLUSIONS: Meta-analysis demonstrates that IHC is highly sensitive and specific for the detection of BRAF-V600E in melanoma cases. IHC is likely to be useful in BRAF mutation detection because it is highly comparable with the genetic methods. Any negative or low staining cases may be selected to undergo genetic analysis based on other clinical and histopathologic features. PMID- 27363651 TI - Protective effects of naringenin in cardiorenal syndrome. AB - BACKGROUND: Cardiorenal syndrome is a complicated and bidirectional interrelationship between the heart and kidneys. Naringenin (NG) is a naturally occurring flavonoid possessing various biological and pharmacological properties. MATERIALS AND METHODS: We tested whether NG could improve cardiac and renal function in a rat model of cardiorenal syndrome. RESULTS: The results showed that NG-attenuated cardiac remodeling and cardiac dysfunction in rats with cardiorenal syndrome, as evidenced by decrease of left ventricle weight (LVW), increase of body weight (BW), decrease of LVW/BW, decrease of concentrations of serum creatinine, blood urea nitrogen, type-B natriuretic peptide, aldosterone, angiotensin (Ang) II, C-reactive protein, and urine protein, increase of left ventricular systolic pressure and falling rates of left ventricular pressure (dp/dtmax), and decrease of left ventricular diastolic pressure, left ventricular end-diastolic pressure, and -dp/dtmax. NG significantly inhibited the increase of lipid profiles including low-density lipoprotein, TC, and TG in rats. In addition, NG significantly inhibited the increase of cardiac expression of IL 1beta, IL-6, and interferon gamma. Moreover, NG decreased malonaldehyde level, increased superoxide dismutase activity and glutathione content in rats, and increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and catalytic subunit of gamma-glutamylcysteine ligase (GCLc) in rats and Ang II treated cardiac fibroblasts. Inhibition of Nrf2 and glutathione synthesis significantly suppressed NG-induced decrease of ROS level. Inhibition of Nrf2 markedly suppressed NG-induced increase of GCLc expression in Ang II-treated cardiac fibroblasts. CONCLUSIONS: The data provide novel options for therapy of patients and new insights into the cardioprotective effects of NG in cardiorenal syndrome. PMID- 27363652 TI - Point-of-care thromboelastography/thromboelastometry-based coagulation management in cardiac surgery: a meta-analysis of 8332 patients. AB - OBJECTIVES: Severe bleeding related to cardiac surgery is associated with increased morbidity and mortality. Thromboelastography (TEG) and thromboelastometry (ROTEM) are point-of-care tests (POCT). Bedside ROTEM/TEG can rapidly detect changes in blood coagulation and therefore provide a goal directed, individualized coagulation therapy. In this meta-analysis, we aimed to determine the current evidence for or against POCT-guided algorithm in patients with severe bleeding after cardiac surgery. METHODS: We performed a meta-analysis of randomized controlled trials and observational trials retrieved from a literature search in PubMed, EMBASE, and Cochrane Library. Only trials comparing transfusion strategy guided by TEG/ROTEM with a standard of care control group undergoing cardiac surgery were included. In addition, at least one clinical outcome had to be mentioned: mortality, surgical re-exploration rate, sternal wound infection, and acute kidney injury (AKI). Also, surrogate parameters such as transfusion requirements and amount of blood loss were analyzed. The pooled treatment effects (odds ratio [OR] and 95% confidence intervals [CI]) were assessed using a fixed or random-effects model. RESULTS: The literature search retrieved a total of 17 trials (nine randomized controlled trial and eight observational trials) involving 8332 cardiac surgery patients. POCT-guided transfusion management significantly decreased the odds for patients to receive allogeneic blood products (OR 0.63, 95% CI 0.56-0.71; P < 0.00001) and the re exploration rate due to postoperative bleeding (OR 0.56, 95% CI 0.45-0.71; P < 0.00001). Furthermore, the incidence of postoperative AKI (OR 0.77, 95% CI 0.61 0.98; P = 0.0278) and thromboembolic events (OR 0.44, 95% CI 0.28-0.70; P = 0.0006) was significantly decreased in the TEG/ROTEM group. No statistical differences were found with regard to inhospital mortality, cerebrovascular accident, or length of intensive care unit and hospital stay. CONCLUSIONS: TEG/ROTEM-based coagulation management decreases the risk of allogeneic blood product exposure after cardiac surgery. Furthermore, it results in significantly lower re-exploration rate, decreased incidence of postoperative AKI, and thromboembolic events in cardiac surgery patients. Results of this meta-analysis indicate that POCT-guided transfusion therapy is superior to the current standard of care. PMID- 27363653 TI - MiR-330-5p regulates tyrosinase and PDIA3 expression and suppresses cell proliferation and invasion in cutaneous malignant melanoma. AB - BACKGROUND: Increasing evidence has suggested that miR-330-5p can function as a tumor suppressor in different types of cancers. However, the effects and underlying mechanisms of miR-330-5p in the development of cutaneous malignant melanoma (CMM) remain largely unknown. The aim of the present study was to investigate the role of miR-330-5p in CMM and to determine the molecular mechanisms underlying its action. MATERIALS AND METHODS: The expression level of miR-330-5p was detected in 26 cases of primary CMM tissues and cell lines by real time quantitative polymerase chain reaction. We also assessed whether overexpression of miR-330-5p influences in vitro cell proliferation, invasion, and migration. Western blotting analysis was used to detect the influence of miR 330-5p on the targets, and Pearson analysis was used to calculate the correlation between the expression of targets gene and miR-330-5p in CMM tissues. RESULTS: Our study showed that miR-330-5p was downregulated in CMM tissues (P = 0.010) and cell lines (P < 0.05), and patients with high mitotic activity showed lower miR 330-5p expression levels (P = 0.002). Enforced expression of miR-330-5p inhibits malignant CMM cells proliferation and migration and led to downregulation of the TYR and PDIA3 protein. Moreover, the expression level of miR-330-5p in CMM tissues showed inverse relationship with the expression level of TYR and PDIA3 protein. CONCLUSIONS: In conclusion, our findings suggested that miR-330-5p represents a potential tumor-suppressive miRNA and plays an important role in CMM progression by suppressing TYR and PDIA3 expression. PMID- 27363654 TI - Impact of stroma LOXL2 overexpression on the prognosis of intrahepatic cholangiocarcinoma. AB - BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is associated with a poor prognosis related to early recurrence especially in the remnant liver after surgery. ICC exhibits a dense desmoplastic stroma which plays a pivotal role in ICC aggressiveness. Thus, analyzing gene deregulation in the stroma of ICC may help to identify new prognosis biomarkers and promising therapeutic targets. The aim of this study was to evaluate the clinical relevance of the matrix-remodeling enzyme lysyl oxidase-like 2 (LOXL2) expression in ICC. MATERIAL AND METHODS: LOXL2 messenger RNA levels were evaluated in microdissected tumoral stroma (TS) and in nontumoral fibrous tissue by gene expression profiling (testing set, n = 10) obtained from gene expression omnibus database and by quantitative real time polymerase chain reaction (validating set, n = 6). LOXL2 protein levels were evaluated by immunohistochemistry on a tissue microarray containing 80 independent patients. The relationship between LOXL2 expression and survival was assessed by univariate and multivariate analyses. RESULTS: LOXL2 messenger RNA levels were increased in TS, both in the testing and the validating sets (P < 0.01). These results were confirmed at a protein level, with a significantly higher LOXL2 immunostaining in TS (P < 0.01). Univariate analysis revealed that LOXL2 expression was correlated with a poor overall survival and disease-free survival (P < 0.01). Importantly, high expression of LOXL2 was an independent prognostic factor of worst overall survival (hazard ratio = 5.29, confidence interval [CI] 95% = 1.71-16.3, P < 0.01) and disease-free survival (hazard ratio = 5.55, CI 95% = 2.14-14.37, P < 0.01). CONCLUSIONS: Our study provides additional arguments for a role of extracellular matrix remodeling in ICC aggressiveness and identifies LOXL2 as a new prognostic marker and a promising therapeutic target in ICC. PMID- 27363655 TI - Liver regeneration after different degrees of portal vein ligation. AB - BACKGROUND: Selective portal vein ligation (PVL) is followed by ipsilateral atrophy and contralateral hypertrophy of the liver lobes. Although the atrophy hypertrophy complex induced by PVL is a well-documented phenomenon, the effect of different degrees of extended portal vein occlusion on liver regeneration is not known. The aim of this study was to assess the effects of different degrees of portal occlusion on portal pressure and liver regeneration. MATERIALS AND METHODS: Male Wistar rats (n = 96; 220-250 g) were randomized into three groups and underwent 70%, 80%, or 90% portal vein ligation, respectively. The portal pressure was measured immediately and 24, 48, 72, 120, and 168 h after PVL (n = 6/group/time point). The hepatic lobes and the spleen were weighed, and liver regeneration ratio was calculated. Changes in liver histology and the mitotic activity were assessed on hematoxylin-eosin stained slides. RESULTS: Higher degree of portal occlusion triggered a stronger regenerative response (regeneration ratio of PVL 70%168h = 2.23 +/- 0.13, PVL 80%168h = 3.11 +/- 0.37, PVL 90%168h = 4.68 +/- 0.48) PVL led to an immediate increase in portal pressure, the value of which changed proportionally to the mass of liver tissue deprived of portal perfusion (PVL 70%acute = 17 +/- 2 mm Hg, PVL 80%acute = 19 +/- 1 mm Hg, PVL 90%acute = 26 +/- 4 mm Hg). Findings in histology showed necro-apoptotic lesions in the atrophic liver lobes and increased mitotic cell count in the hypertrophic lobes. The mitotic cell count of PVL 90% peaked earlier and at a significantly higher value than of PVL 70% and PVL 80% (PVL 9024h%: 96.0 +/- 3.5 PVL 70%48h: 64.0 +/- 2.1, PVL 80%48h: 56.3 +/- 4.0). The mitotic index after 24 h showed a strong correlation with the acute portal hypertension. CONCLUSIONS: A higher degree of portal vein occlusion leads to a greater regenerative response, presumably triggered by the proportional increase in portal pressure, which supports the role of the so-called "blood-flow" theory of PVL-triggered liver regeneration. PMID- 27363656 TI - Cost of ventral hernia repair using biologic or synthetic mesh. AB - BACKGROUND: Patients undergoing ventral hernia repair (VHR) with biologic mesh (BioM) have higher hospital costs compared with synthetic mesh (SynM). This study compares 90-d pre- and post-VHR hospital costs (180-d) among BioM and SynM based on infection risk. METHODS: This retrospective National Surgical Quality Improvement Program study matched patient perioperative risk with resource utilization cost for a consecutive series of VHR repairs. Patient infection risks, clinical and financial outcomes were compared in unmatched SynM (n = 303) and BioM (n = 72) groups. Propensity scores were used to match 35 SynM and BioM pairs of cases with similar infection risk for outcomes analysis. RESULTS: BioM patients in the unmatched group were older with higher American Society of Anesthesiologists (ASA) and wound classification, and they more frequently underwent open repairs for recurrent hernias. Wound surgical site infections were more frequent in unmatched BioM patients (P = 0.001) as were 180-d costs ($43.8k versus $14.0k, P < 0.001). Propensity matching resulted in 31 clean cases. In these low-risk patients, wound occurrences and readmissions were identical, but 180-d costs remained higher ($31.8k versus $15.5k, P < 0.001). There were no differences in hospital 180-d diagnostic, emergency room, intensive care unit, floor, pharmacy, or therapeutic costs. However, 180-d operating room services and supply costs were higher in the BioM group ($21.1k versus $7.1k, P < 0.001). CONCLUSIONS: BioM is used more commonly in hernia repairs involving higher wound class and ASA scores and recurrent hernias. Clinical outcomes after low-risk VHRs are similar; SynM utilization in low-risk hernia repairs was more cost-effective. PMID- 27363657 TI - Tracheal occlusion and ventilation changes the nitric oxide pathway in congenital diaphragmatic hernia model. AB - BACKGROUND: Congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia and pulmonary hypertension. Tracheal occlusion (TO) stimulates fetal lung growth and maturation and reverse vascular changes responsible for pulmonary hypertension, which are related to mechanisms involving nitric oxide (NO) in CDH. We aim to evaluate the effect of TO and ventilation on NO pathways. METHODS: Eight groups were created: (1) control; (2) control ventilated (CV); (3) CDH (CDH); (4) CDH ventilated (CDHV); (5) TO control; (6) TO ventilated; (7) TO + CDH; and (8) TO + CDH ventilated (CDHTOV). Fetuses were weighed, and volume ventilated for 30 min after harvested. Total lung weight and the ratio of total lung weight to body weight, thickness of the middle layer of the pulmonary arteriole, and the air space diameter were measured. The NO synthase inducible and NO synthase inducible were performed by immunohistochemistry and Western blotting. RESULTS: The total lung weight and the ratio of total lung weight to body weight decreased in animals with nitrofen and also after ventilation for all groups (P < 0.05). The thickness of the middle layer of the pulmonary arteriole decreased in all groups with TO when compared with controls (P < 0.001). The air space diameter decreased after ventilation in the CDHTOV compared to the TO + nitrofen-induced CDH (P < 0.001). Compared to nonventilated cohorts, NO synthase inducible increased in CV and TO ventilated (P < 0.001) and decreased in CDHV and CDHTOV (P < 0.001). NO synthase inducible increased in CV and CDHV (P < 0.001) and decreased in the TO control and CDHTOV (P < 0.001). CONCLUSIONS: TO and ventilation alter the NO pathway with possible implications in reducing the pulmonary hypertension in CDH. PMID- 27363658 TI - Survival advantage depends on cecal volume rather than cecal length in a mouse model of cecal ligation and puncture. AB - BACKGROUND: Cecal ligation and puncture (CLP) is the most commonly used model to simulate human polymicrobial sepsis. However, the severity of CLP is difficult to be standardized across different laboratories. The aim of the present study was to evaluate the influence of ligated cecal volume and length on mortality in mouse CLP model. METHODS: Cecal length and volume were measured from 120 Kunming mice subjected to CLP or sham operation. According to cecal volume, mice were divided into three groups, volume0.0~0.2 (0.0 cm(3)-0.2 cm(3)), volume0.2~0.4 (0.2 cm(3)-0.4 cm(3)), and volume>0.4 (larger than 0.4 cm(3)). The contents of cytokines, including interleukin-1beta, interleukin-6, and TNF-alpha, were measured at 3 h after surgery. The blood bacterial load and oxidative stress indicators (including malondialdehyde and superoxide dismutase) were measured at 12 h after surgery. RESULTS: There was no significant difference on 72-h survival rate between the mice with cecum longer than 2 cm and shorter than 2 cm. Compared to the other volume groups, volume>0.4 group showed significantly increased blood bacterial load, malondialdehyde levels in lung and liver, and pro-inflammatory cytokines in serum. Surprisingly, the survival rate in volume>0.4 (0%) group showed significant difference from those of volume0.0~0.2 group (40%) and volume0.2~0.4 group (40%). CONCLUSIONS: The mice in volume>0.4 group have much serious inflammatory reaction and are easier to die. As the proportion of volume>0.4 mice is near 20%, it can have large influence on most of the related studies using this CLP model. PMID- 27363660 TI - Negative pressure therapy is effective in abdominal incision closure. AB - BACKGROUND: CDC wound classification demonstrates surgical site infection (SSI) occurs in 15%-30% of contaminated (class III) and >30% of dirty-infected (class IV) wounds. Several techniques have been used to decrease SSI rates in midline laparotomy incisions; however, no technique has shown superiority. Evidence suggests incisional negative pressure wound therapy (INPWT) can decrease wound complications, but no literature exists regarding INPWT for high-risk laparotomy incisions. We sought to analyze the efficacy of INPWT in the management of high risk midline laparotomy incisions. METHODS: Retrospective review of adult patients who underwent laparotomy between January 2013 and June 2014 with midline closure using INPWT. Only class III or IV wounds were included. Laparotomy incisions were loosely closed. INPWT set at 125 mm Hg is placed over oil emulsion impregnated gauze. INPWT is removed after 5 d and the wound left open to air. Records were reviewed for immediate and/or delayed surgical site complications. Primary end point was 30-d incisional SSI. Secondary end points included other surgical site complications. RESULTS: One class III and 12 class IV wounds were treated with INPWT for a median of 5 d. The class III wound developed a small skin dehiscence with no evidence of superficial or deep SSI. Among class IV wounds, the rate of superficial and deep incisional SSI was 25% and 0%, respectively. The overall surgical site complication rate was 41.7%. CONCLUSIONS: INPWT in closure of high-risk midline laparotomy incisions is a safe, effective method of wound closure with equivalent SSI rates to previously described methods. PMID- 27363659 TI - Hyperglycemia attenuates remifentanil postconditioning-induced cardioprotection against hypoxia/reoxygenation injury in H9c2 cardiomyoblasts. AB - BACKGROUND: Hyperglycemia is proposed to be an independent risk factor for cardiovascular morbidity and mortality. Preclinical studies suggest that diabetes mellitus exacerbates myocardial ischemia/reperfusion injury and attenuates the effects of cardioprotective strategies. The cardioprotective effects of postconditioning with the opioid analgesic remifentanil against ischemia/reperfusion injury under the hyperglycemic condition remain contradictory. Therefore, the aim of this study was to investigate the mechanisms by which hyperglycemia affects cardioprotection induced by remifentanil postconditioning. MATERIALS AND METHODS: H9c2 cardiomyoblasts were cultured under the normoglycemic or hyperglycemic condition. Cells were exposed to hypoxia/reoxygenation (H/R) injury followed by hypoxia postconditioning (HPC group) or remifentanil postconditioning (RPC group). Cell viability, injury, and apoptosis were measured after each postconditioning treatment. Activation of endoplasmic reticulum stress (ERS) was analyzed by examining the protein levels of GRP78, CHOP, cleaved caspase-12 and cleaved caspase-3. RESULTS: RPC significantly increased cell viability and reduced apoptosis in normoglycemic cardiomyoblasts, but not in hyperglycemic cardiomyoblasts. HPC and RPC markedly decreased the upregulation of GRP78, CHOP, cleaved caspase 12, and cleaved caspase 3 in response to H/R injury under the normoglycemic condition. Hyperglycemia significantly increased these ERS-associated biomarkers and apoptosis, which could not be reduced by HPC or RPC. CONCLUSIONS: Remifentanil postconditioning protected cardiomyoblasts from H/R injury under normoglycemia, at least in part, through inhibiting ERS-induced apoptosis. Hyperglycemia attenuated the cardioprotection conferred by remifentanil postconditioning, likely as a result of the exacerbated ERS. Inhibiting the ERS response may be an attractive strategy to enhance the cardioprotective effects of postconditioning in diabetic patients. PMID- 27363661 TI - Complication timing impacts 30-d mortality after hepatectomy. AB - BACKGROUND: To date, no study has specifically focused on the timing of complications after hepatectomy relative to patient outcomes. We sought to investigate the effect of complication timing on 30-d mortality. MATERIALS AND METHODS: A total of 3064 patients who underwent hepatic resection in 2014 were identified from American College of Surgeons National Surgical Quality Improvement Program database. Cox regression analysis was performed to determine the association of complication timing with 30-d mortality. RESULTS: Median patient age was 60 y (interquartile range, 50-68). Among all patients who experienced a complication, 16.6% had only a postdischarge complication. Wound disruption (64%) and surgical site infection (58.1%) occurred frequently after discharge. Organ space surgical site infection occurred at a later time after surgery among patients who underwent minimally invasive surgery (minimally invasive surgery, 16 d versus open 10 d; P = 0.008). Among 47 (1.5%) patients who died within 30 d from surgery, 21.3% of deaths occurred postdischarge. After adjusting for competing risk factors, patients who had experienced a postdischarge complication demonstrated an increased risk of 30-d mortality (referent, predischarge, hazard ratio 2.96, 95% confidence intervals 1.07-8.17; P = 0.04). CONCLUSIONS: Postdischarge complications occurred less frequently after hepatectomy than predischarge complications; however, late complications were associated with a three-fold increased risk of mortality. PMID- 27363662 TI - Fabrication of hexagonally patterned flower-like silver particle arrays as surface-enhanced Raman scattering substrates. AB - Hierarchical assembly of plasmonic nanostructures can induce high surface enhanced Raman scattering (SERS) activity. However, it is a challenge to uniformly disperse the hierarchical nanostructures onto a planar substrate to achieve SERS signal reproducibility. This report presents a facile route to fabricate a hexagonally patterned flower-like silver particle array as the SERS substrate. First, hexagonally ordered silver hemisphere arrays with smooth surface are molded in the pores of an anodic aluminum oxide template. Ag nanosheets are then electrodeposited onto the surface of individual silver hemispheres. The numerous nano-edges and nano-gaps between adjacent nanosheets render a large number of hot spots, leading to high SERS activity over a larger area of chip. The silver flower-like array is employed as the SERS substrate, which is able to detect 0.1 nM rhodamine 6 G and 1 MUM 3,3',4,4' tetrachlorobiphenyl (PCB-77, a persistent organic pollutant). PMID- 27363663 TI - Mechanism of antiproliferative action of a new d-secoestrone-triazole derivative in cervical cancer cells and its effect on cancer cell motility. AB - Cervical cancer is the fourth most frequently diagnosed tumor and the fourth leading cause of cancer death in females worldwide. Cervical cancer is predominantly related with human papilloma virus (HPV) infection, with the most oncogenic types being HPV-18 and -16. Our previous studies demonstrated that some d-secoestrone derivatives exert pronounced antiproliferative activity. The aim of the current investigation was to characterize the mechanism of action of d secoestrone-triazole (D-SET) on three cervical cancer cell lines with different pathological backgrounds. The growth-inhibitory effects of D-SET were determined by a standard MTT assay. We have found that D-SET exerts a pronounced growth inhibitory effect on HPV 18-positive HeLa and HPV-negative C-33 A cells, but it has no substantial inhibitory activity on HPV 16-positive SiHa or on intact fibroblast MRC-5 cell lines. After 24h incubation, cells showed the morphological and biochemical signs of apoptosis determined by fluorescent double staining, flow cytometry and caspase-3 activity assay. Besides the elevation of the ratio of cells in the subG1 phase, flow cytometric analysis revealed a cell cycle arrest at G2/M in both HeLa and C-33 A cell lines. To distinguish the G2/M cell population immunocytochemical flow cytometric analysis was performed on HeLa cells. The results show that D-SET significantly increases the ratio of phosphorylated histone H3, indicating cell accumulation in the M phase. Additionally, D-SET significantly increased the maximum rate of microtube formation measured by an in vitro tubulin polymerization assay. Besides its direct antiproliferative activity, the antimigratory property of D-SET has been investigated. Our results demonstrate that D-SET significantly inhibits the migration and invasion of HeLa cells after 24h incubation. These results suggests that D-SET is a potent antiproliferative agent against HPV 16+ and HPV-negative cervical cancer cell lines, with an efficacious motility-inhibiting activity against HPV 16+ cells. Accordingly D-SET can be regarded as a potential drug candidate with a promising new mechanism of action among the antiproliferative steroids, potentially allowing for the design of novel anticancer agents. PMID- 27363664 TI - Selectivity of solid phase extraction of freshwater dissolved organic matter and its effect on ultrahigh resolution mass spectra. AB - Solid phase extraction (SPE) is often used for enrichment and clean-up prior to analysis of dissolved organic matter (DOM) by electrospray ionization (ESI) coupled to ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). It is generally accepted that extraction by SPE is not quantitative with respect to carbon concentration. However, little information is available on the selectivity of different SPE sorbents and the resulting effect for the acquired DOM mass spectra. Freshwater samples were extracted by the widely used PPL, HLB and C18 sorbents and the molecular composition and size distribution of the DOM in the extracts and in the permeates was compared to the original sample. Dissolved organic carbon (DOC) recoveries ranged between 20% and 65% for the three tested SPE sorbents. Size-exclusion chromatography coupled to organic carbon detection (SEC-OCD) revealed that limited recovery by PPL and HLB was primarily due to incomplete elution of a fraction of apparent high molecular weight from the solid phase. In contrast, incomplete retention on the solid phase, mainly observed for the C18 cartridge, was attributed to a fraction of low molecular weight. The FT-ICR mass spectra of the original sample and the SPE extracts did not differ significantly in their molecular weight distribution, but they showed sorbent specific differences in the degree of oxygenation and saturation. We concluded that the selective enrichment of freshwater DOM by SPE is less critical for subsequent FT-ICR MS analysis, because those fractions that are not sufficiently recovered have comparatively small effects on the mass spectra. This was confirmed by the extraction of model compounds, showing that very polar and small molecules are poorly extracted, but also have a low response in ESI-MS. Of the three tested SPE cartridges the PPL material offered the best properties for DOM enrichment for subsequent FT-ICR MS analysis as it minimizes too strong and too weak DOM-sorbent interactions. PMID- 27363665 TI - Cationic palladium(ii)-catalyzed dehydrative nucleophilic substitutions of benzhydryl alcohols with electron-deficient benzenethiols in water. AB - An efficient direct nucleophilic substitution of benzhydryl alcohols with electron-deficient benzenethiols using cationic Pd(ii) catalysts as Lewis acids in water is reported. Atom economical and environmentally benign protocols afford S-benzylated products in moderate to excellent yields. Commercially available Pd(MeCN)4(OTf)2, PdCl2(MeCN)2, and Na2PdCl4 are highly efficient catalysts. Notably, this simple protocol can be achieved without any other additives such as acids, bases, or external ligands. A Hammett study on the rate constants of S benzylation by using various substituted benzhydryl alcohols yielded negative rho values, suggesting that there is a build-up of positive charge in the transition state. PMID- 27363666 TI - [Synergistic activity and clinical efficacy of fosfomycin and ciprofloxacin combination treatment for soft tissue infection caused by carbapenemase-producing Enterobacter cloacae]. PMID- 27363667 TI - Snail represses the expression of human phospholipid scramblase 4 gene. AB - Human phospholipid scramblases (hPLSCRs) are a group of transmembrane ATP independent lipid transporters mediating bi-directional transport of phospholipids. There are four homologues hPLSCR1-hPLSCR4 and hPLSCR1 is the extensively studied homologue among them. hPLSCR4 shares 48% homology with hPLSCR1 and mediates scrambling of PLs similar to hPLSCR1 in Ca(2+) dependent manner. Transcriptional regulation helps in better understanding of the function and the expression of a protein. Till date there are no reports suggesting the transcriptional regulation of hPLSCR4. In this study, we identified Snail to be a potent regulator of hPLSCR4. ConSite tool predicted the presence of a putative Snail binding site with a consensus sequence of (-1521)CAGGTG(-1516) on hPLSCR4 promoter. Luciferase assays depicted a dose dependent decrease in hPLSCR4 promoter activity with an increase in amount of Snail. Deletion analysis revealed that the region from -1380 to -2100 to be the regulatory region of hPLSCR4. Knock down studies further confirmed Snail mediated downregulation of hPLSCR4, as the mRNA and the protein levels of hPLSCR4 considerably increased under knock down conditions. The in vivo interaction of Snail with hPLSCR4 promoter was further confirmed by ChIP assay. This is the first report on the transcriptional regulation of hPLSCR4, where Snail was shown to downregulate the expression of hPLSCR4. PMID- 27363668 TI - Pm-miR-133 hosting in one potential lncRNA regulates RhoA expression in pearl oyster Pinctada martensii. AB - Long non-coding RNAs (LncRNAs) are abundant in the genome of higher forms of eukaryotes and implicated in regulating the diversity of biological processes partly because they host microRNAs (miRNAs), which are repressors of target gene expression. In vertebrates, miR-133 regulates the differentiation and proliferation of cardiac and skeletal muscles. Pinctada martensii miR-133 (pm-miR 133) was identified in our previous research through Solexa deep sequencing. In the present study, the precise sequence of mature pm-miR-133 was validated through miR-RACE. Stem loop qRT-PCR analysis demonstrated that mature pm-miR-133 was constitutively expressed in the adductor muscle, gonad, hepatopancreas, mantle, foot, and gill of P. martensii. Among these tissues, the adductor muscle exhibited the highest pm-miR-133 expression. Target analysis indicated that pm RhoA was the potential regulatory target of pm-miR-133. Bioinformatics analyses revealed that a potential LncRNA (designated as Lnc133) with a mature pm-miR-133 could generate a hairpin structure that was highly homologous to that of Lottia gigantea. Lnc133 was also highly expressed in the adductor muscle, gill, hepatopancreas, and gonad. Phylogenetic analysis further showed that the miR-133s derived from chordate and achordate were separated into two classes. Therefore, Lnc133 hosting pm-miR-133 could be involved in regulating the cell proliferation of adductor muscles by targeting pm-RhoA. PMID- 27363669 TI - The study of filaggrin gene mutations and copy number variation in atopic dermatitis patients from Volga-Ural region of Russia. AB - Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by age-specific localization, dryness, itch and hypersensitivity to allergens. In our study, we investigated FLG gene mutations and CNVs in AD patients and control subjects of different ethnic origin from Volga-Ural region. AD group included 303 patients (177 Russians, 126 Tatars). Control group consisted of 261 healthy individuals (152 Russians, 109 Tatars). The study revealed 66 FLG mutation carriers and demonstrated an association between c.2282del4 deletion and AD development in Russians and Tatars of Volga-Ural region of Russia. In the analysis of the FLG gene CNVs, the most common was 10-repeat allele in both Russian and Tatar patients and controls. We were unable to find any significant difference in CNV repeats count between AD patients and control individuals. PMID- 27363670 TI - Towards Enhanced Performance Thin-film Composite Membranes via Surface Plasma Modification. AB - Advancing the design of thin-film composite membrane surfaces is one of the most promising pathways to deal with treating varying water qualities and increase their long-term stability and permeability. Although plasma technologies have been explored for surface modification of bulk micro and ultrafiltration membrane materials, the modification of thin film composite membranes is yet to be systematically investigated. Here, the performance of commercial thin-film composite desalination membranes has been significantly enhanced by rapid and facile, low pressure, argon plasma activation. Pressure driven water desalination tests showed that at low power density, flux was improved by 22% without compromising salt rejection. Various plasma durations and excitation powers have been systematically evaluated to assess the impact of plasma glow reactions on the physico-chemical properties of these materials associated with permeability. With increasing power density, plasma treatment enhanced the hydrophilicity of the surfaces, where water contact angles decreasing by 70% were strongly correlated with increased negative charge and smooth uniform surface morphology. These results highlight a versatile chemical modification technique for post treatment of commercial membrane products that provides uniform morphology and chemically altered surface properties. PMID- 27363671 TI - Limited Quantum Helium Transportation through Nano-channels by Quantum Fluctuation. AB - Helium at low temperatures has unique quantum properties such as superfluidity, which causes it to behave differently from a classical fluid. Despite our deep understanding of quantum mechanics, there are many open questions concerning the properties of quantum fluids in nanoscale systems. Herein, the quantum behavior of helium transportation through one-dimensional nanopores was evaluated by measuring the adsorption of quantum helium in the nanopores of single-walled carbon nanohorns and AlPO4-5 at 2-5 K. Quantum helium was transported unimpeded through nanopores larger than 0.7 nm in diameter, whereas quantum helium transportation was significantly restricted through 0.4-nm and 0.6-nm nanopores. Conversely, nitrogen molecules diffused through the 0.4-nm nanopores at 77 K. Therefore, quantum helium behaved as a fluid comprising atoms larger than 0.4-0.6 nm. This phenomenon was remarkable, considering that helium is the smallest existing element with a (classical) size of approximately 0.27 nm. This finding revealed the presence of significant quantum fluctuations. Quantum fluctuation determined the behaviors of quantum flux and is essential to understanding unique quantum behaviors in nanoscale systems. PMID- 27363672 TI - A three-coordinate Fe(ii) center within a [3Fe-(MU3-S)] cluster that provides an accessible coordination site. AB - A MU3-sulfide bridged triiron cluster(ii,ii,iii) supported by a cyclophane ligand undergoes metal-based reduction to yield an all-ferrous species. The latter complex incorporates a three-coordinate iron center that provides an accessible coordination site to a solvent molecule. PMID- 27363673 TI - Editorial: Centennial Celebration - An Interview with Dr Perrin White on Pediatric Endocrinology. PMID- 27363674 TI - CORRIGENDUM FOR 10.1210/me.2015-1007. PMID- 27363677 TI - Disproportionality in Power Plants' Carbon Emissions: A Cross-National Study. AB - Past research on the disproportionality of pollution suggests a small subset of a sector's facilities often produces the lion's share of toxic emissions. Here we extend this idea to the world's electricity sectors by calculating national-level disproportionality Gini coefficients for plant-level carbon emissions in 161 nations based on data from 19,941 fossil-fuel burning power plants. We also evaluate if disproportionalities in plant-level emissions are associated with increased national carbon emissions from fossil-fuel based electricity production, while accounting for other well-established human drivers of greenhouse gas emissions. Results suggest that one potential pathway to decreasing nations' greenhouse gas emissions could involve reducing disproportionality among fossil-fuel power plants by targeting those plants in the upper end of the distribution that burn fuels more inefficiently to produce electricity. PMID- 27363678 TI - Potential role of nuclear PD-L1 expression in cell-surface vimentin positive circulating tumor cells as a prognostic marker in cancer patients. AB - Although circulating tumor cells (CTCs) have potential as diagnostic biomarkers for cancer, determining their prognostic role in cancer patients undergoing treatment is a challenge. We evaluated the prognostic value of programmed death ligand 1 (PD-L1) expression in CTCs in colorectal and prostate cancer patients undergoing treatment. Peripheral blood samples were collected from 62 metastatic colorectal cancer patients and 30 metastatic prostate cancer patients. CTCs were isolated from the samples using magnetic separation with the cell-surface vimentin(CSV)-specific 84-1 monoclonal antibody that detects epithelial mesenchymal transitioned (EMT) CTCs. CTCs were enumerated and analyzed for PD-L1 expression using confocal microscopy. PD-L1 expression was detectable in CTCs and was localized in the membrane and/or cytoplasm and nucleus. CTC detection alone was not associated with poor progression-free or overall survival in colorectal cancer or prostate cancer patients, but nuclear PD-L1 (nPD-L1) expression in these patients was significantly associated with short survival durations. These results demonstrated that nPD-L1 has potential as a clinically relevant prognostic biomarker for colorectal and prostate cancer. Our data thus suggested that use of CTC-based models of cancer for risk assessment can improve the standard cancer staging criteria and supported the incorporation of nPD-L1 expression detection in CTCs detection in such models. PMID- 27363680 TI - Critical Slowing of Density Fluctuations Approaching the Isotropic-Nematic Transition in Liquid Crystals: 2D IR Measurements and Mode Coupling Theory. AB - Two-dimensional infrared (2D IR) data are presented for a vibrational probe in three nematogens: 4-cyano-4'-pentylbiphenyl, 4-cyano-4'-octylbiphenyl, and 4 (trans-4-amylcyclohexyl)-benzonitrile. The spectral diffusion time constants in all three liquids in the isotropic phase are proportional to [T*/(T - T*)](1/2), where T* is 0.5-1 K below the isotropic-nematic phase transition temperature (TNI). Rescaling to a reduced temperature shows that the decays of the frequency frequency correlation function (FFCF) for all three nematogens fall on the same curve, suggesting a universal dynamic behavior of nematogens above TNI. Spectral diffusion is complete before significant orientational relaxation in the liquid, as measured by optically heterodyne detected-optical Kerr effect (OHD-OKE) spectroscopy, and before any significant orientational randomization of the probe measured by polarization selective IR pump-probe experiments. To interpret the OHD-OKE and FFCF data, we constructed a mode coupling theory (MCT) schematic model for the relationships among three correlation functions: phi1, a correlator for large wave vector density fluctuations; phi2, the orientational correlation function whose time derivative is the observable in the OHD-OKE experiment; and phi3, the FFCF for the 2D IR experiment. The equations for phi1 and phi2 match those in the previous MCT schematic model for nematogens, and phi3 is coupled to the first two correlators in a straightforward manner. Resulting models fit the data very well. Across liquid crystals, the temperature dependences of the coupling constants show consistent, nonmonotonic behavior. A remarkable change in coupling occurs at ~5 K above TNI, precisely where the rate of spectral diffusion in 5CB was observed to deviate from that of a similar nonmesogenic liquid. PMID- 27363679 TI - Dairy cheese consumption ameliorates single-meal sodium-induced cutaneous microvascular dysfunction by reducing ascorbate-sensitive oxidants in healthy older adults. AB - Chronic dairy product intake is associated with improved cardiovascular outcomes, whereas high dietary Na impairs endothelial function through increased oxidative stress and reduced nitric oxide (NO) bioavailability. The purpose of this study was to compare the effect of acute cheese consumption with consumption of Na from non-dairy sources on microvascular function. We hypothesised that dairy cheese ingestion would augment NO-dependent vasodilation compared with Na from non-dairy sources. On five visits, fourteen subjects (61 (sem 2) years, eight male/six female) consumed either 85 g dairy cheese (560 mg Na), 85 g soya cheese (560 mg Na), 65 g pretzels (560 mg Na), 170 g dairy cheese (1120 mg Na) or 130 g pretzels (1120 mg Na). Two intradermal microdialysis fibres were inserted in the ventral forearm for delivery of lactated Ringer's solution or 10 mm-ascorbate (antioxidant) during local skin heating (approximately 50 min). Erythrocyte flux was measured continuously by laser-Doppler flowmetry (LDF), and cutaneous vascular conductance (CVC=LDF/mean arterial pressure) was normalised as %CVCmax (28 mm-sodium nitroprusside). Following a plateau in CVC, 15 mm-N G -nitro-l arginine-methyl-ester was perfused to quantify NO-dependent vasodilation (approximately 45 min). NO-dependent vasodilation was greater following consumption of dairy products (560 mg Na 57 (sem 3) %) (1120 mg Na 55 (sem 5) %) compared with soya (560 mg Na 42 (sem 3) %; P=0.002) or pretzels (560 mg Na 43 (sem 4) %; P=0.004) (1120 mg Na 46 (sem 3) %; P=0.04). Ascorbate augmented NO dependent vasodilation following intake of soya (control: 42 (sem 3) v. ascorbate: 54 (sem 3) %; P=0.01) or pretzels (560 mg Na; control: 43 (sem 4) v. ascorbate: 56 (sem 3) %; P=0.006) (1120 mg Na; control: 46 (sem 5) v. ascorbate: 56 (sem 3) %; P=0.02), but not dairy products. Na ingestion via dairy products was associated with greater NO-dependent vasodilation compared with non-dairy products, a difference that was ameliorated with ascorbate perfusion. The antioxidant properties of dairy proteins may protect against Na-induced reductions in NO-dependent dilation. PMID- 27363681 TI - Involvement of the pagR gene of pXO2 in anthrax pathogenesis. AB - Anthrax is a disease caused by Bacillus anthracis. Specifically, the anthrax toxins and capsules encoded by the pXO1 and pXO2 plasmids, respectively, are the major virulence factors. We previously reported that the pXO1 plasmid was retained in the attenuated strain of B. anthracis vaccine strains even after subculturing at high temperatures. In the present study, we reinvestigate the attenuation mechanism of Pasteur II. Sequencing of pXO1 and pXO2 from Pasteur II strain revealed mutations in these plasmids as compared to the reference sequences. Two deletions on these plasmids, one each on pXO1 and pXO2, were confirmed to be unique to the Pasteur II strain as compared to the wild-type strains. Gene replacement with homologous recombination revealed that the mutation in the promoter region of the pagR gene on pXO2, but not the mutation on pXO1, contributes to lethal levels of toxin production. This result was further confirmed by RT-PCR, western blot, and animal toxicity assays. Taken together, our results signify that the attenuation of the Pasteur II vaccine strain is caused by a mutation in the pagR gene on its pXO2 plasmid. Moreover, these data suggest that pXO2 plasmid encoded proteins are involved in the virulence of B. anthracis. PMID- 27363683 TI - Meeting report: Pre-exposure Human Immunodeficiency Virus Prophylaxis in the EU/EEA: Challenges and Opportunities, Stockholm April 2016. PMID- 27363684 TI - Validation of Immunomonitoring Methods for Application in Clinical Studies: The HLA-Peptide Multimer Staining Assay. AB - BACKGROUND: Validated assays are essential to generate data with defined specificity, consistency, and reliability. Although the process of validation is required for applying immunoassays in the context of clinical studies, reports on systematic validation of in vitro T cell assays are scarce so far. We recently validated our HLA-peptide multimer staining assay in a systematic manner so as to qualify the method for monitoring antigen-specific T cell responses after immunotherapy. METHODS: Parameters of the assay, specificity, precision, linearity, sensitivity, and robustness were assessed systematically. Experiments were designed to address specifically each parameter and are detailed. RESULTS: Nonspecific multimer staining was below the acceptance limit of 0.02% multimer(+) CD8(+) cells. The assay showed acceptable precision in all dimensions it was repeated (CV < 10%) and also demonstrated a linear detection (R2 > 0.99) of antigen specific cells. CONCLUSIONS: We succeeded in validating the HLA-multimer staining assay in a systematic manner. Additionally, we propose a technical framework and recommendations that can be applied for validating other T cell assessment methods. (c) 2016 International Clinical Cytometry Society. PMID- 27363685 TI - Role of Interleukin-10 (-1082A/G) gene polymorphism with the risk of ischemic stroke: a meta-analysis. AB - The role of anti-inflammatory Interleukin-10 (IL-10) cytokine gene polymorphism with the risk of ischemic stroke (IS) remains controversial. The aim of present meta-analysis was to investigate the association of IL-10 (-1082 A/G) gene polymorphism with the risk of IS. A literature search for candidate gene association studies published before 29 February 2016 was conducted in the PubMed, EMBASE, Google Scholar, and TRIP database. The following search terms were used: 'Interleukin-10' or 'IL-10' and 'Ischemic stroke' or 'IS' and 'Cerebral Infarction' or 'CI' and 'genetic polymorphism' or 'single nucleotide polymorphisms' or 'SNP'. Fixed or random effects models were used to estimate the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Begg's funnel plot was used to assess the potential for publication bias. In our meta-analysis, five case-control studies involving 1209 IS cases and 1139 controls were included. Overall, there was no significant association between IL-10 (-1082 A/G) [rs1800896] and risk of IS under dominant [AA + AG vs. GG], recessive [AA vs. AG + GG], and allelic [G vs.A] models. However, based on Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, we observed significant association of IL-10 (-1082 A/G) gene polymorphism with the risk of IS for Large Vessel Disease (LVD), Small Vessel Disease (SVD), and other (others due to determined and undetermined etiology) subtypes of IS. This is the first meta-analysis to conclude that IL-10-1082A/G gene polymorphism is associated with the risk of LVD, SVD, and other subtypes of IS. Further well-designed large sample size studies based on TOAST classification are needed to validate these findings. PMID- 27363686 TI - Characterizing social communication changes in amyotrophic lateral sclerosis. AB - BACKGROUND: Speech and language impairments are well-established in individuals with amyotrophic lateral sclerosis (ALS). However, knowledge about particular aspects of social communication and everyday conversational abilities is limited. AIMS: To investigate self- and informant-report ratings of social communicative abilities in ALS participants and matched healthy controls. METHODS & PROCEDURES: Thirty-two participants with ALS and 24 controls completed the La Trobe Communication Questionnaire (LCQ). Participants nominated a close other to provide an informant report on the LCQ. Demographic and clinical information was also collected. OUTCOMES & RESULTS: Informant ratings indicated greater difficulties in conversational initiation, effectiveness and partner sensitivity for ALS participants compared with controls. ALS participants did not rate their social communicative abilities as poorer than controls and self-reports only differed from informant ratings in the control group. LCQ scores were not significantly correlated with clinical/functional variables. CONCLUSIONS & IMPLICATIONS: Social communication can be reduced in ALS and individuals may lack insight into these difficulties. In order to understand and provide targeted interventions for such difficulties, clinical speech and language assessment should incorporate social communication assessment, including both a self- and informant-report format. PMID- 27363687 TI - Systematic review with meta-analysis: the efficacy of levofloxacin triple therapy as the first- or second-line treatments of Helicobacter pylori infection. AB - BACKGROUND: Levofloxacin triple therapy has been used for the first-line and second-line treatment of Helicobacter pylori infection for more than 10 years. AIMS: To systematically review the efficacy of levofloxacin triple therapy in the first- and second-line treatment, and to assess the time trend and factors that might affect its efficacy. METHODS: Prospective trials reporting the efficacy of levofloxacin triple therapy in either the first-line or second-line treatment of H. pylori infection in adults were searched from the PubMed and Cochrane database from January 2000 to September 2015. Meta-analysis was performed to calculate the cumulative eradication rate and the efficacies in subgroups. RESULTS: Of the 322 articles identified, a total of 4574 patients from 41 trials, including 16 trials in the first-line treatment and 25 trials in the second-line treatment were eligible for analysis. The cumulative eradication rate was 77.3% (95% confidence intervals, CI: 74.7-79.6) and was 80.7% (95% CI 77.1-83.7) in the first-line treatment and 74.5% (95% CI: 70.9-77.8) in the second-line treatment. The efficacies of levofloxacin triple therapy before 2008, between 2009 and 2011, and after 2012 were 77.4%, 79.6% and 74.8% respectively. The eradication rate was higher when levofloxacin was given once daily (80.6%, 95% CI: 77.1-83.7) than twice daily (73.6%, 95% CI: 69.7-77.2). The efficacy was significantly higher in levofloxacin-susceptible strains than resistant strains (81.1% vs. 36.3%, risk ratio 2.18, 95% CI: 1.6-3, P < 0.001). CONCLUSION: The efficacy of levofloxacin triple therapy has been lower than 80% in many countries and it is not recommended when the levofloxacin resistance is higher than 5-10%. PMID- 27363682 TI - Genome-wide association study identifies multiple susceptibility loci for multiple myeloma. AB - Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 * 10(-8)), 6q21 (rs9372120, P=9.09 * 10(-15)), 7q36.1 (rs7781265, P=9.71 * 10(-9)), 8q24.21 (rs1948915, P=4.20 * 10(-11)), 9p21.3 (rs2811710, P=1.72 * 10( 13)), 10p12.1 (rs2790457, P=1.77 * 10(-8)), 16q23.1 (rs7193541, P=5.00 * 10(-12)) and 20q13.13 (rs6066835, P=1.36 * 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development. PMID- 27363688 TI - The eyes have it: Eye movements and anorexia nervosa. PMID- 27363689 TI - Domino Radical Addition/Oxidation Sequence with Photocatalysis: One-Pot Synthesis of Polysubstituted Furans from alpha-Chloro-Alkyl Ketones and Styrenes. AB - A new domino reaction has been developed that allows the combination of styrenes and alpha-alkyl ketone radicals to afford a wide array of polysubstituted furans in good to excellent yields under mild and simple reaction conditions. The key to success of this novel protocol is the use of photocatalyst fac-Ir(ppy)3 and oxidant K2 S2 O8 . Mechanistic studies by a radical scavenger and photoluminescence quenching suggest that a radical addition/oxidation pathway is operable. PMID- 27363690 TI - Who Spends Money to Play for Free? Identifying Who Makes Micro-transactions on Social Casino Games (and Why). AB - Social casino games are online gambling-like games found on social networking sites. They are initially free to play, however, players are encouraged to make micro-transactions (i.e., in-game purchases) for additional game credits or functionality. As a result, they generate billions of dollars in revenue. Yet, little is known as to who purchases virtual credits, let alone why. In the present research, we assessed whether there are individual differences (impulsivity, reward sensitivity, competitiveness, and problem gambling severity) between who is and who is not likely to make micro-transactions during social casino game play. Moreover, we examined possible motivations for making micro transactions (e.g., extend play, win back lost credits) and whether the individual difference variables of interest predict reported motivation(s) for making micro-transactions. Results showed that social casino gamers who engaged in micro-transactions reported significantly higher levels of impulsivity, reward sensitivity and problem gambling severity, but not competitiveness. In terms of motivation to make micro-transactions, desire to extend play was endorsed most frequently, followed by a desire to access additional features, chasing lost credits, and to speed up play. Lastly, among participants who made micro transactions, reward sensitivity predicted making micro-transactions to chase lost credits. These results suggest the personality make-up of social casino gamers is important to understand who is likely to make micro-transactions as well as their motivation to do so-information that could prove useful for regulation of the industry. PMID- 27363691 TI - Ten-year follow-up of health-related quality of life among ambulatory persons with multiple sclerosis at baseline. AB - PURPOSE: The aim of this 10-year follow-up study was to determine changes in health-related quality of life (HRQoL) over time among ambulatory persons with MS (PwMS) at the baseline using generic and disease-specific instruments. METHODS: Of 109 independently walking PwMS included in a population-based study in 2002, 77 (70.6 %) were re-assessed in 2012. HRQoL was captured using the 36-Item Short Form Survey Instrument (RAND-36), 15D instrument (15D), and the Multiple Sclerosis Quality of Life-54 (MSQOL-54). Repeated-measures ANOVA and effect size (ES) calculations (Cohen's d) were used in the statistical analysis. RESULTS: The RAND-36 physical health composite score (p = 0.003, ES = 0.26) and 15D total score (p = 0.012, ES = 0.25) declined from the baseline levels. In particular, lower scores were observed on the RAND-36 scales of physical functioning (p = 0.001, ES = 0.27), pain (p = 0.020, ES = 0.25), and general health perceptions (p = 0.002, ES = 0.36), on the MSQOL-54 scales of physical functioning (p = 0.001, ES = 0.27), pain (p = 0.040, ES = 0.21), sexual functioning (p = 0.003, ES = 0.43), and satisfaction with sexual functioning (p = 0.012, ES = 0.38), and in the 15D dimensions of mobility (p = 0.004, ES = 0.31) and sexual functioning (p <= 0.001, ES = 0.59). Improvement was observed on the RAND-36 scale of social functioning (p = 0.049, ES = 0.25). The other composite scores, scales, and dimensions remained unchanged. CONCLUSION: The results of this study suggest that ambulatory PwMS at baseline reported reduced HRQoL in physical functioning after a 10-year follow-up period, while emotional well-being was maintained and social functioning improved. The scores in the other HRQoL dimensions and scales remained unchanged. More long-term population-based studies are needed to precisely determine the development of HRQoL among PwMS. PMID- 27363692 TI - Associations between daily physical activity, handgrip strength, muscle mass, physical performance and quality of life in prefrail and frail community-dwelling older adults. AB - PURPOSE: The aim of this study was to examine the associations between daily physical activity (DPA), handgrip strength, appendicular skeletal muscle mass (ASMM) and physical performance (balance, gait speed, chair stands) with quality of life in prefrail and frail community-dwelling older adults. METHODS: Prefrail and frail individuals were included, as determined by SHARE-FI. Quality of life (QoL) was measured with WHOQOL-BREF and WHOQOL-OLD, DPA with PASE, handgrip strength with a dynamometer, ASMM with bioelectrical impedance analysis and physical performance with the SPPB test. Linear regression models adjusted for sex and age were developed: In model 1, the associations between each independent variable and QoL were assessed separately; in model 2, all the independent variables were included simultaneously. RESULTS: Eighty-three participants with a mean age of 83 (SD: 8) years were analysed. Model 1: DPA (beta = 0.315), handgrip strength (beta = 0.292) and balance (beta = 0.178) were significantly associated with 'overall QoL'. Balance was related to the QoL domains of 'physical health' (beta = 0.371), 'psychological health' (beta = 0.236), 'environment' (beta = 0.253), 'autonomy' (beta = 0.276) and 'social participation' (beta = 0.518). Gait speed (beta = 0.381) and chair stands (beta = 0.282) were associated with 'social participation' only. ASMM was not related to QoL. Model 2: independent variables explained 'overall QoL' (R 2 = 0.309), 'physical health' (R 2 = 0.200), 'autonomy' (R 2 = 0.247) and 'social participation' (R 2 = 0.356), among which balance was the strongest indicator. CONCLUSION: ASMM did not play a role in the QoL context of the prefrail and frail older adults, whereas balance and DPA were relevant. These parameters were particularly associated with 'social participation' and 'autonomy'. PMID- 27363693 TI - Asymmetric responsiveness of disability and health-related quality of life to improvement versus decline in Parkinson's disease. AB - PURPOSE: Clinical trials in Parkinson's disease commonly employ outcome measures of disability and quality of life. Responsiveness of these outcomes measures to symptomatic decline versus improvement has not been studied. We wanted to study the responsiveness of Schwab & England Activities of Daily Living Scale (SE) and Short Form-12 (SF-12) to symptomatic decline versus improvement in Parkinson's disease over a 4-year period among a naturalistic cohort of patients. METHODS: Parkinson's disease patients (N = 228, disease duration 6.1 years) were followed for 4 years with assessments of disease severity, Unified Parkinson's Disease Rating Scale (UPDRS), health-related quality of life (SF-12 physical/mental health), and disability (SE). The sample was subdivided into those who declined (N = 118) or improved (N = 102) on total-UPDRS. Responsiveness was assessed with Cohen's effect size and standardized response mean. RESULTS: At baseline, patients who improved over 4 years had greater disease severity and worse quality of life than decliners (p < .05). Decliners had a 13.5-point worsening on total UPDRS, 26.3-39.8; p < .001) associated with concomitant decline on the SF-12 (physical health 42.9-39.2, mental health 50.0-46.6; both p < .001) and the SE (85-74 %; p < .001). Improvers had a 13.0-point improvement on total-UPDRS (39.8 26.8; p < .001) associated with minimal change on the SF-12 (physical health 40.8 39.5, mental health 47.1-46.3) and SE (79-79 %). Based on effect size, the rank order of responsiveness of measures for decliners from high to low was SE ( 0.78), Short Form-12 mental health (-0.45), and SF-12 physical health (-0.34). Rank order of responsiveness for improvers was Short Form-12 physical health ( 0.11), SF-12 mental health (-0.10), and SE (-0.03). CONCLUSIONS: Among decliners, measures of disability and quality of life were moderate to highly responsive to change in disease severity. Among improvers, both disability and quality of life were poorly responsive despite UPDRS improvement of comparable magnitude. PMID- 27363694 TI - Polymorphisms in the Pattern Recognition Receptor Mincle Gene (CLEC4E) and Association with Tuberculosis. AB - The mechanisms involved in interactions between Mycobacterium tuberculosis and host innate immune cells determine outcome. Antigen-presenting cells, including macrophages and dendritic cells, express many pattern recognition receptors to identify pathogen-associated molecular patterns, thereby initiating an immune response. A major mycobacterial virulence factor, trehalose-6',6-dimycolate, is recognised by the macrophage-inducible C-type lectin, Mincle, which leads to the activation of the Syk-Card9 signalling pathway in macrophages. Mincle is encoded by CLEC4E, and we investigated polymorphisms in this gene to assess its role in tuberculosis susceptibility. Four tagging single nucleotide polymorphisms (SNPs) (rs10841845, rs10841847, rs10841856 and rs4620776) were genotyped using TaqMan((r)) SNP assays in 416 tuberculosis cases and 405 healthy controls. Logistic regression models were used for analysis. No association was detected with any of the SNPs analysed. This research highlights tuberculosis disease complexity where recognition proteins which specifically bind mycobacterial glycolipids cannot be conclusively associated with the disease in genetic studies. PMID- 27363695 TI - Effects of Environmental Pollutants on MCF-7 Cells: A Metabolic Approach. AB - Several environmental pollutants (EPs) have been associated with biological and molecular processes leading to adverse human health effects, including different types of cancer. Nevertheless, the effects exerted on tumor glucose metabolism are unclear. To evaluate the effects on cellular and molecular mechanisms, namely glucose metabolism, MCF-7 cells were exposed to EPs during short- and long-term exposures. The effect of both, organochlorine pesticides and plasticizing agents, on glucose uptake by MCF-7 cells was not dose-dependent and was affected by time of exposure. The SigmaHCH and BPA increased glucose uptake after 20 min. Long term exposure to 250 nM of organochlorine pesticides (p,p'-DDE and SigmaHCH) and BPA increased cell proliferation. However, only the organochlorine pesticides were able to increase lactate production, without a concomitant higher glucose uptake or glycolytic enzymes transcription. Given their distinct persistent profiles, the biological significance of their exposure should be considered accordingly. J. Cell. Biochem. 118: 366-375, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27363696 TI - Alteplase Treatment in Acute Stroke: Incorporating Food and Drug Administration Prescribing Information into Existing Acute Stroke Management Guide. AB - Despite strong evidence that intravenous tissue plasminogen activator (tPA) improves outcomes in acute ischemic stroke patients, its use in clinical practice remains modest. Complex eligibility criteria have been postulated as barriers to greater utilization. Further complicating this has been multiple guidelines and prescribing labels that have been published since first being approved for use in 1996. In this review, several warning and exclusion criteria for tPA in acute ischemic stroke are reviewed with the goal of providing readers a nuanced understanding of historical context and available evidence to make informed decision. PMID- 27363698 TI - The next generation of clinical leaders; future proofing preparation. PMID- 27363697 TI - Immunotherapy targeting pyroglutamate-3 Abeta: prospects and challenges. AB - Immunization against amyloid-beta (Abeta) peptides deposited in Alzheimer's disease (AD) has shown considerable therapeutic effect in animal models however, the translation into human Alzheimer's patients is challenging. In recent years, a number of promising Abeta immunotherapy trials failed to reach primary study endpoints. Aside from uncertainties in the selection of patients and the start and duration of treatment, these results also suggest that the mechanisms underlying AD are still not fully understood. Thorough characterizations of protein aggregates in AD brain have revealed a conspicuous heterogeneity of Abeta peptides enabling the study of the toxic potential of each of the major forms. One such form, amino-terminally truncated and modified pyroglutamate (pGlu)-3 Abeta peptide appears to play a seminal role for disease initiation, qualifying it as novel target for immunotherapy approaches. PMID- 27363699 TI - Negative correlation between tumour size and cortisol/ACTH ratios in patients with Cushing's disease harbouring microadenomas or macroadenomas. AB - PURPOSE: Pituitary macroadenomas (MACs) represent 10-30 % of Cushing's disease (CD) cases. The aim of this study was to report the clinical, laboratorial and imaging features and postsurgical outcomes of microadenoma (MIC) and MAC patients. METHODS: Retrospective study with 317 CD patients (median 32 years old, range 9-71 years) admitted between 1990 and 2014, 74 (23.3 %) of whom had MAC. RESULTS: Hirsutism, plethora facial, muscular weakness and muscular atrophy were more frequent in the MIC patients. Nephrolithiasis, osteopenia, hyperprolactinaemia and galactorrhoea were more prevalent in MAC patients. The morning serum cortisol (Fs), nocturnal salivary cortisol (NSC), nocturnal Fs (Fs 2400 h), low- and high-dose dexamethasone suppression test results and CRH and desmopressin test results were similar between the subgroups. MIC patients showed higher urinary cortisol at 24 h (UC), and MAC patients presented higher ACTH levels but lower Fs/ACTH, Fs 2400 h/ACTH, NSC/ACTH and UC/ACTH ratios. There were negative correlations of tumour size with Fs/ACTH, Fs 2400 h/ACTH, NSC/ACTH and UC/ACTH ratios. Overall, the postsurgical remission and recurrence rates were similar between MIC and MAC. However, patients in remission (MIC + MAC) showed smaller tumour diameters and a lower prevalence of invasion and extension on MRI. CONCLUSIONS: Despite exhibiting higher plasma ACTH levels, CD patients with MAC presented lower cortisol/ACTH ratios than did patients with MIC, with a negative correlation between tumour size and cortisol/ACTH ratios. The overall postsurgical remission and recurrence rates were similar between MIC and MAC patients, with those with larger and/or invasive tumours showing a lower remission rate. PMID- 27363700 TI - HER2 Status in Gastric Cancer: Comparison between Primary and Distant Metastatic Disease. AB - HER2 (human epidermal growth factor receptor-2) assessment in histological samples of gastric cancer is essential to determine which patients might benefit from trastuzumab therapy. HER2 is often evaluated in primary tumor even if trastuzumab therapy is used to treat metastatic disease. However, the exact relationship in terms of HER2 status between primary and metastatic tumors has not been fully clarified. We aimed to evaluate the HER2 status concordance between primary gastric cancer and corresponding distant metastasis. HER2 status was evaluated by IHC (immunohistochemistry) and/or FISH ( fluorescence in situ hybridization) in 41 patients in primary gastric cancer and in paired metastasis. HER2 was assessed according scoring criteria applied in clinical approach. HER2 positivity was found in 14,6 % primary tumors and in 24,4%corresponding metastasis. HER2 concordance rate between primary and metastasis was 80,5 % (K value = 0,388). Eight/41 (19,5 %)cases resulted discordant: 6 patients with metastatic HER2 positive lesions were found HER2 negative in primary cancers while 2 patient HER2 positive in primary lesion showed a negative conversion in metastasis. Our results showed a good concordance in terms of HER2 status between primary and metastatic lesions, as well as in biopsy and surgical removed specimens. However, the higher rate of HER2 positive status found in metastatic lesions underlined the importance of HER2 assessment in all samples obtained from different sites of gastric cancer disease. PMID- 27363701 TI - Dosimetric advantages of proton therapy over conventional radiotherapy with photons in young patients and adults with low-grade glioma. AB - BACKGROUND AND PURPOSE: Low-grade glioma (LGG) is a very common brain tumor in pediatric patients typically associated with a very good prognosis. This prognosis makes it imperative that the risk of long-term treatment-related side effects be kept at an absolute minimum. Proton therapy (PRT) provides a radiation technique that has the potential to further reduce the genesis of radiogenic impairment. MATERIALS AND METHODS: We retrospectively assessed 74 patients with LGG who underwent PRT. Conventional three-dimensional photon and PRT plans were generated after contouring structures of neurogenesis, crucial neuronal structures, and areas susceptible to secondary malignancies. Target volume coverage was evaluated using the homogeneity index (HI) and inhomogeneity coefficient (IC). Results were compared using the Wilcoxon-signed rank test, with p < 0.05 being statistically significant. RESULTS: Target volume coverage was comparable for the photon and proton plans. Overall, we could show an essential reduction in maximal, mean, and integral doses in critical neurologic structures, areas of neurogenesis, and structures of neurocognitive function. The study indicated specifically how contralaterally located structures could be spared with PRT. CONCLUSION: PRT is a highly conformal radiation technique offering superior dosimetric advantages over conventional radiotherapy by allowing significant dose reduction for organs at risk (OAR) that are essential for neurologic function, neurocognition, and quality of life, thus demonstrating the potential of this technique for minimizing long-term sequelae. PMID- 27363702 TI - Betaine enhances antidepressant-like, but blocks psychotomimetic effects of ketamine in mice. AB - Ketamine is emerging as a new hope against depression, but ketamine-associated psychotomimetic effects limit its clinical use. An adjunct therapy along with ketamine to alleviate its adverse effects and even potentiate the antidepressant effects might be an alternative strategy. Betaine, a methyl derivative of glycine and a dietary supplement, has been shown to have antidepressant-like effects and to act like a partial agonist at the glycine site of N-methyl-D-aspartate receptors (NMDARs). Accordingly, betaine might have potential to be an adjunct to ketamine treatment for depression. The antidepressant-like effects of ketamine and betaine were evaluated by forced swimming test and novelty suppressed feeding test in mice. Both betaine and ketamine produced antidepressant-like effects. Furthermore, we determined the effects of betaine on ketamine-induced antidepressant-like and psychotomimetic behaviors, motor incoordination, hyperlocomotor activity, and anesthesia. The antidepressant-like responses to betaine combined with ketamine were stronger than their individual effects. In contrast, ketamine-induced impairments in prepulse inhibition, novel object recognition test, social interaction, and rotarod test were remarkably attenuated, whereas ketamine-induced hyperlocomotion and loss of righting reflex were not affected by betaine. These findings revealed that betaine could enhance the antidepressant-like effects, yet block the psychotomimetic effects of ketamine, suggesting that betaine can be considered as an add-on therapy to ketamine for treatment-resistant depression and suitable for the treatment of depressive symptoms in patients with schizophrenia. PMID- 27363703 TI - Evaluation of an FDA approved library against laboratory models of human intestinal nematode infections. AB - BACKGROUND: Treatment options for infections with soil-transmitted helminths (STH) - Ascaris lumbricoides, Trichuris trichiura and the two hookworm species, Ancylostoma duodenale and Necator americanus - are limited despite their considerable global health burden. The aim of the present study was to test the activity of an openly available FDA library against laboratory models of human intestinal nematode infections. METHODS: All 1,600 drugs were first screened against Ancylostoma ceylanicum third-stage larvae (L3). Active compounds were scrutinized and toxic compounds, drugs indicated solely for topical use, and already well-studied anthelmintics were excluded. The remaining hit compounds were tested in parallel against Trichuris muris first-stage larvae (L1), Heligmosomoides polygyrus third-stage larvae (L3), and adult stages of the three species in vitro. In vivo studies were performed in the H. polygyrus and T. muris mice models. RESULTS: Fifty-four of the 1,600 compounds tested revealed an activity of > 60 % against A. ceylanicum L3 (hit rate of 3.4 %), following incubation at 200 MUM for 72 h. Twelve compounds progressed into further screens. Adult A. ceylanicum were the least affected (1/12 compounds active at 50 MUM), while eight of the 12 test compounds revealed activity against T. muris L1 (100 MUM) and adults (50 MUM), and H. polygyrus L3 (200 MUM). Trichlorfon was the only compound active against all stages of A. ceylanicum, H. polygyrus and T. muris. In addition, trichlorfon achieved high worm burden reductions of 80.1 and 98.9 %, following a single oral dose of 200 mg/kg in the T. muris and H. polygyrus mouse model, respectively. CONCLUSION: Drug screening on the larval stages of intestinal parasitic nematodes is feasible using small libraries and important given the empty drug discovery and development pipeline for STH infections. Differences and commonalities in drug activities across the different STH species and stages were confirmed. Hits identified might serve as a starting point for drug discovery for STH. PMID- 27363705 TI - Mortality After Atrioventricular Nodal Radiofrequency Catheter Ablation With Permanent Ventricular Pacing in Atrial Fibrillation: Outcomes From a Controlled Nonrandomized Study. AB - BACKGROUND: Atrioventricular nodal radiofrequency ablation (AVNA) with permanent ventricular pacing can be used to control rate in patients with atrial fibrillation (AF). However, long-term outcomes after AVNA are uncertain, especially in light of irreversible pacemaker dependence. METHODS AND RESULTS: We examined 9122 consecutive patients with AF. The outcomes in 453 patients with AVNA (26% of whom underwent an implantable cardiac defibrillator implant and 37% underwent cardiac resynchronization therapy implant) were compared with AF patients without AVNA after propensity score 1:1 matching. During follow-up in the propensity-matched cohort (2.41+/-3.23 years, median 1.23, quartiles 0.33 3.12), 100 patients died (yearly rate of death 6.6%). Mode of death was available in 86% of patients, which was cardiovascular in 67% of the patients (related to heart failure in 38%, sudden death in 5%, and other cardiovascular reason in 24%) and noncardiovascular in 33%. AVNA in patients with AF was associated with a lower risk of mortality (odds ratio 0.47, 95% confidence interval, 0.29-0.77; P=0.003), a lower risk of cardiovascular mortality (odds ratio =0.41, 95% confidence interval 0.23-0.73; P=0.003), and nonsignificant lower risk of stroke and thromboembolic events (odds ratio =0.61, 95% confidence interval 0.36-1.06; P=0.08). CONCLUSIONS: In sick AF patients with multiple comorbidities, AVNA with permanent ventricular pacing for rate control seems safe during follow-up and may be associated with lower mortality. PMID- 27363704 TI - Gene expression analysis of metallothionein and mineral elements uptake in tomato (Solanum lycopersicum) exposed to cadmium. AB - Heavy metals such as Cd are considered to be the most important pollutants in soil contamination. Cd is a non-essential element adversely affecting plant growth and development, and it has caused some physiological and molecular changes. Metallothioneins (MTs) are low molecular weight, cysteine-rich, and metal binding proteins. In this study, we aimed to evaluate the MT gene expression levels and minerals uptake in the tissues of Solanum lycopersicum exposed to Cd. The transcriptional expression of the MT genes was determined by real-time quantitative PCR. The MT genes were regulated by the Cd and the mineral elements uptake changed tissue type and applied doses. The MT1 and MT2 transcript levels increased in the roots, the leaves and the fruits of the tomato. The MT3 and MT4 transcript pattern changed according to the tissue types. The Cd treatment on the growth medium increased the Mg, Ca, and Fe content in both the leaves and fruits of the tomato. However, the Cd affected the mineral levels in the roots depending on the mineral types and doses. Also, the Cd content increased in the roots, the leaves, and the fruits of the tomato, respectively. The results presented in this study show that Cd has synergistic and/or antagonistic effects on minerals depending on the tissue types. These results indicate that the MT1 and MT2 expression pattern increased together with the Mg, Ca, and Fe content in both the leaves and the fruits of the tomato. PMID- 27363706 TI - Validation of combinatorial probe-anchor ligation-based sequencing as non invasive prenatal test for trisomy at a central laboratory. AB - OBJECTIVE: To evaluate the clinical validity of a new ultrahigh-throughput non invasive prenatal test (NIPT) based on combinatorial probe-anchor ligation (cPAL) sequencing of cell-free fetal DNA (cffDNA) using centralized testing. METHODS: Maternal plasma samples were obtained from 10 594 singleton pregnancies in high risk populations at 20 centers in China, including 8155 that were collected retrospectively and 2439 prospectively. Fetal outcome data and karyotyping results were documented as gold standard and were double blinded during NIPT. The clinical performance of the ultrahigh-throughput sequencing method, cPAL, for NIPT was validated by evaluating its sensitivity, specificity and positive predictive value (PPV) in detecting trisomies 21, 18 and 13 as the centralized testing mode in the reference laboratory. To ensure stable and reproducible performance of centralized cPAL-based NIPT in detecting trisomies, a series of quality-control systems, including sequencing of two sets of artificial samples, were employed and evaluated. RESULTS: Ten prospective cases were excluded from the study because of incomplete clinical data. Four prospective samples failed to generate a NIPT result due to assay failure, presenting a failure rate of 0.16% (4/2429). A total of 168 retrospective cases and 47 prospective cases had a positive NIPT result for trisomy, giving respective positive rates of 2.06% and 1.94%. Four false-positive and no false-positive cases were observed in the retrospective and prospective groups, respectively, resulting in PPV of 97.62% (95% CI, 94.02-99.35%) and 100% (95% CI, 92.45-100%), respectively. In the retrospective group, sensitivity and specificity were, respectively, 100% (95% CI, 97.07-100%) and 99.98% (95% CI, 99.94-100%) for trisomy 21, 100% (95% CI, 97.75-100%) and 99.98% (95% CI, 99.94-100%) for trisomy 18, and 100% (95% CI, 15.81-100%) and 100% (95% CI, 99.95-100%) for trisomy 13. In the prospective group, sensitivity and specificity were, respectively, 100% (95% CI, 90.75-100%) and 100% (95% CI, 99.85-100%) for trisomy 21, 100% (95% CI, 63.06-100%) and 100% (95% CI, 99.85-100%) for trisomy 18, and 100% (95% CI, 2.50-100%) and 100% (95% CI, 99.85-100%) for trisomy 13. CONCLUSION: In this multicenter study with a full quality-control system, NIPT by centralized cPAL-based testing showed high stability and performance comparable to those of previous validation studies in high-risk populations. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27363707 TI - Differential free fatty acid receptor-1 (FFAR1/GPR40) signalling is associated with gene expression or gelatinase granule release in bovine neutrophils. AB - Fatty acids have been recognized as regulators of immune function in addition to their known metabolic role. Long-chain fatty acids bind free fatty acid receptor (FFAR)-1/GPR40, which is expressed on bovine neutrophils, and increase responses such as granule release and gene expression. In this study, we investigated the molecular mechanisms governing the up-regulation of cyclooxygenase-2 (COX-2) and IL-8, as well as matrix metalloproteinase (MMP)-9 granule release in FFAR1/GPR40 agonist-stimulated neutrophils. Our results showed that natural (oleic and linoleic acid) and synthetic (GW9508) FFAR1/GPR40 agonists increased ERK1/2, p38 MAPK and Akt phosphorylation, and that the FFAR1/GPR40 antagonist GW1100 reduced these responses. We evaluated the levels of IkappaBalpha, a component of the classical activation pathway of the transcription factor NF-kappaB, and we observed IkappaBalpha reduction after stimulation with FFAR1/GPR40 agonists, an effect that was inhibited by GW1100 or the inhibitors UO126, SB203580 or LY294002. FFAR1/GPR40 agonists increased COX-2 and IL-8 expression, which was inhibited by GW1100 and an NF-kappaB inhibitor. Finally, the FFAR1/GPR40 agonist induced MMP-9 granule release was reduced by GW1100 and UO126. In conclusion, FFAR1/GPR40 agonists differentially stimulate neutrophil functions; COX-2 and IL 8 are expressed after FFAR1/GPR40 activation via NF-kappaB, IkappaBalpha reduction is FFAR1/GPR40- and PI3K/MAPK-dependent, and MMP-9 granule release is FFAR1/GPR40- and ERK1/2-dependent. PMID- 27363708 TI - [Histological grading of breast cancer]. AB - From a historical perspective, histological grading was the earliest cell-based method for assessing tumor biology and the prognosis of breast cancer. This review article provides detailed and practical instructions for grading of breast cancer in routine diagnostics. Furthermore, the increasing relevance of precise histological grading in the era of molecular pathology is discussed. PMID- 27363709 TI - Comment on: World Kidney Day 2016: averting the legacy of kidney disease-focus on childhood. PMID- 27363710 TI - Occurrence of neutrophil dysplasia in the course of severe nephrotic syndrome in a 12-year-old boy on immunosuppressive therapy: Questions. PMID- 27363711 TI - Occurrence of neutrophil dysplasia in the course of severe nephrotic syndrome in a 12-year-old boy on immunosuppressive therapy: Answers. PMID- 27363712 TI - Reply to comment on World Kidney Day 2016: averting the legacy of kidney disease focus on childhood. PMID- 27363713 TI - Inhibition in motor imagery: a novel action mode switching paradigm. AB - Motor imagery requires that actual movements are prevented (i.e., inhibited) from execution. To investigate at what level inhibition takes place in motor imagery, we developed a novel action mode switching paradigm. Participants imagined (indicating only start and end) and executed movements from start buttons to target buttons, and we analyzed trial sequence effects. Trial sequences depended on current action mode (imagination or execution), previous action mode (pure blocks/same mode, mixed blocks/same mode, or mixed blocks/other mode), and movement sequence (action repetition, hand repetition, or hand alternation). Results provided evidence for global inhibition (indicated by switch benefits in execution-imagination (E-I)-sequences in comparison to I-I-sequences), effector specific inhibition (indicated by hand repetition costs after an imagination trial), and target inhibition (indicated by target repetition benefits in I-I sequences). No evidence for subthreshold motor activation or action-specific inhibition (inhibition of the movement of an effector to a specific target) was obtained. Two (global inhibition and effector-specific inhibition) of the three observed mechanisms are active inhibition mechanisms. In conclusion, motor imagery is not simply a weaker form of execution, which often is implied in views focusing on similarities between imagination and execution. PMID- 27363714 TI - Effects of Within-Talker Variability on Speech Intelligibility in Mandarin Speaking Adult and Pediatric Cochlear Implant Patients. AB - Cochlear implant (CI) speech performance is typically evaluated using well enunciated speech produced at a normal rate by a single talker. CI users often have greater difficulty with variations in speech production encountered in everyday listening. Within a single talker, speaking rate, amplitude, duration, and voice pitch information may be quite variable, depending on the production context. The coarse spectral resolution afforded by the CI limits perception of voice pitch, which is an important cue for speech prosody and for tonal languages such as Mandarin Chinese. In this study, sentence recognition from the Mandarin speech perception database was measured in adult and pediatric Mandarin-speaking CI listeners for a variety of speaking styles: voiced speech produced at slow, normal, and fast speaking rates; whispered speech; voiced emotional speech; and voiced shouted speech. Recognition of Mandarin Hearing in Noise Test sentences was also measured. Results showed that performance was significantly poorer with whispered speech relative to the other speaking styles and that performance was significantly better with slow speech than with fast or emotional speech. Results also showed that adult and pediatric performance was significantly poorer with Mandarin Hearing in Noise Test than with Mandarin speech perception sentences at the normal rate. The results suggest that adult and pediatric Mandarin-speaking CI patients are highly susceptible to whispered speech, due to the lack of lexically important voice pitch cues and perhaps other qualities associated with whispered speech. The results also suggest that test materials may contribute to differences in performance observed between adult and pediatric CI users. PMID- 27363715 TI - The Effect of Nicotine and Tobacco on Aortic Matrix Metalloproteinases in the Production of Aortic Aneurysm. AB - BACKGROUND: Aortic aneurysms (AAs) are without effective pharmacologic therapy, in clinical usage, in part because of the limited understanding of factors leading to AA development. OBJECTIVE: The objectives of this study were to examine the evidence that cigarette smoking induces AAs through altering matrix metalloproteinases (MMP) and the molecular biology/pharmacology that maybe involved in this effect. METHODS: A systematic search was conducted to identify studies that examined the links between cigarette smoke, MMP and AAs. RESULTS: Eleven studies were identified. There was consistency, between studies. They found that cigarette smoke, nicotine or tobacco products increased aortic dimension and the proportion of AAs. Nicotine and tobacco constituents induced MMPs: MMP-1, MMP-2, MMP-8, MMP-9 and MMP-12 but with different levels of consistency. The molecular mechanisms involved in the pathogenesis of cigarette induced AA formation, ranked according to the consistency of evidence include JNK, AMPK-alpha2, Jak Stat, and mTOR/p70Sk and PTEN pathways. CONCLUSION: Nicotine and tobacco constituents translate the exposure to cigarette smoke into increased MMP expression through various molecular mechanisms whose interruption can form the basis for pharmacologic management of AAs. PMID- 27363717 TI - Nurofen advertisement was misleading, says watchdog. PMID- 27363716 TI - Mutational Spectrum in Holoprosencephaly Shows That FGF is a New Major Signaling Pathway. AB - Holoprosencephaly (HPE) is the most common congenital cerebral malformation in humans, characterized by impaired forebrain cleavage and midline facial anomalies. It presents a high heterogeneity, both in clinics and genetics. We have developed a novel targeted next-generation sequencing (NGS) assay and screened a cohort of 257 HPE patients. Mutations with high confidence in their deleterious effect were identified in approximately 24% of the cases and were held for diagnosis, whereas variants of uncertain significance were identified in 10% of cases. This study provides a new classification of genes that are involved in HPE. SHH, ZIC2, and SIX3 remain the top genes in term of frequency with GLI2, and are followed by FGF8 and FGFR1. The three minor HPE genes identified by our study are DLL1, DISP1, and SUFU. Here, we demonstrate that fibroblast growth factor signaling must now be considered a major pathway involved in HPE. Interestingly, several cases of double mutations were found and argue for a polygenic inheritance of HPE. Altogether, it supports that the implementation of NGS in HPE diagnosis is required to improve genetic counseling. PMID- 27363718 TI - GFRA Global Foot-and-Mouth Disease Research Update and Gap Analysis. PMID- 27363719 TI - Ovarian function suppression is beneficial in some premenopausal women with early breast cancer. PMID- 27363721 TI - The effects of prenatal "psychological" stressor exposure on lung inflammation and hyperresponsiveness in adult rat offspring. AB - The aim of this study was to establish whether exposure of pregnant rats to uncontrollable (psychological) stressors might change the likelihood of their offspring to exhibit functional and histopathological abnormalities suggestive of asthma in adulthood. Pregnant rats (n = 16) underwent one of three treatments: electric shocks of a maximum duration of 10 s that could be escaped (controllable group; C) those that could not be escaped (uncontrollable group; U) or no shocks (control group; N). The offspring (n = 54) were kept in animal house under standard conditions until 3 months of age, when lung hyperresponsiveness, histopathology, immunohistochemical measurements of the cytokines interleukin (IL) 2, IL-4, IL-5, and IL-13 and actin as well as oxidative stress based on iNOS positive cell counts and isoprostane PGF2alpha contents were assessed. The results showed that prenatal exposure to physical stressors (shocks) caused lung hyperresponsiveness and increased cytokine expression; exposure to uncontrollable shock (group U) had a differential effect on the expression of IL-2, IL-5, and IL 13 in inflammatory cells compared to exposure to controllable shock (group C), which characterizes the "psychological" aspect of stress. The results show that not only stress but also its uncontrollability during gestation might increase the likelihood that the offspring will exhibit functional and histopathological abnormalities suggestive of asthma. These findings strengthen the importance of psychological control with regard to environmental stimuli for the occurrence of several illnesses, suggesting the desirability of integration among various fields of science. PMID- 27363722 TI - Influence of Metals on the Cyanobacterial Community in a Water Supply System in a Tropical Region. AB - This work aimed to study the influence of metals on the temporal dynamics of cyanobacteria community in Carpina Dam (7 degrees 53' 22'' S and 35 degrees 20' 34'' W). Samples were collected from Raw Water Pumping Station at the Water Treatment Station Feira Nova in the city of Feira Nova (Pernambuco, Brazil), from January 2011 to December 2013. The concentration of metals in water (aluminum, antimony, barium, lead, copper, chromium, cadmium, iron, manganese) was determined by atomic absorption spectroscopy in the laboratory. For the identification and counting of cyanobacteria, an inverted optical microscope and Sedgewick-Rafter counting chambers were used. Principal Component Analysis (PCA) was used for recognition of cluster patterns between the studied points. There were variations in abiotic and biotic components in the different years of study. The metals iron, aluminum, barium and manganese had the greatest influence on the temporal dynamics of cyanobacteria in the reservoir. PMID- 27363720 TI - KCa 3.1 upregulation preserves endothelium-dependent vasorelaxation during aging and oxidative stress. AB - Endothelial oxidative stress develops with aging and reactive oxygen species impair endothelium-dependent relaxation (EDR) by decreasing nitric oxide (NO) availability. Endothelial KCa 3.1, which contributes to EDR, is upregulated by H2 O2 . We investigated whether KCa 3.1 upregulation compensates for diminished EDR to NO during aging-related oxidative stress. Previous studies identified that the levels of ceramide synthase 5 (CerS5), sphingosine, and sphingosine 1-phosphate were increased in aged wild-type and CerS2 mice. In primary mouse aortic endothelial cells (MAECs) from aged wild-type and CerS2 null mice, superoxide dismutase (SOD) was upregulated, and catalase and glutathione peroxidase 1 (GPX1) were downregulated, when compared to MAECs from young and age-matched wild-type mice. Increased H2 O2 levels induced Fyn and extracellular signal-regulated kinases (ERKs) phosphorylation and KCa 3.1 upregulation. Catalase/GPX1 double knockout (catalase(-/-) /GPX1(-/-) ) upregulated KCa 3.1 in MAECs. NO production was decreased in aged wild-type, CerS2 null, and catalase(-/-) /GPX1(-/-) MAECs. However, KCa 3.1 activation-induced, N(G) -nitro-l-arginine-, and indomethacin resistant EDR was increased without a change in acetylcholine-induced EDR in aortic rings from aged wild-type, CerS2 null, and catalase(-/-) /GPX1(-/-) mice. CerS5 transfection or exogenous application of sphingosine or sphingosine 1 phosphate induced similar changes in levels of the antioxidant enzymes and upregulated KCa 3.1. Our findings suggest that, during aging-related oxidative stress, SOD upregulation and downregulation of catalase and GPX1, which occur upon altering the sphingolipid composition or acyl chain length, generate H2 O2 and thereby upregulate KCa 3.1 expression and function via a H2 O2 /Fyn-mediated pathway. Altogether, enhanced KCa 3.1 activity may compensate for decreased NO signaling during vascular aging. PMID- 27363723 TI - Randomized controlled trial of a bioabsorbable steroid-releasing implant in the frontal sinus opening. AB - OBJECTIVES/HYPOTHESIS: To assess safety and efficacy of a steroid-releasing implant in improving surgical outcomes when placed in the frontal sinus opening (FSO) following endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). STUDY DESIGN: Prospective, multicenter, randomized, blinded trial using an intrapatient control design. METHODS: Eighty adult (>= 18 years) CRS patients who underwent successful bilateral frontal sinusotomy were randomized to receive a steroid-releasing implant in one FSO, whereas the contralateral control side received no implant. All patients received standard postoperative care. Endoscopic evaluations recorded at 30-days postendoscopic sinus surgery (ESS) were graded real time by clinical investigators and by an independent, blinded sinus surgeon to assess the need for postoperative interventions in the FSO. RESULTS: Implants were successfully placed in all 80 frontal sinuses, resulting in 100% implant delivery success. At 30-days post-ESS, steroid-releasing implants provided a statistically significant (P = 0.0070) reduction in the need for postoperative interventions compared to surgery alone by an independent reviewer, representing 38% relative reduction. Clinical investigators reported statistically significant reduction in this measure at 30 days (P < 0.0001) and 90 days (P = 0.0129). Clinical investigators also reported a 55.6% reduction in the need for oral steroid interventions (P = 0.0015), 75% reduction in the need for surgical interventions (P = 0.0225), 16.7% reduction in inflammation score, 54.3% reduction in restenosis rate (P = 0.0002), and 32.2% greater diameter of FSO (P < 0.0001) on treated sides compared to control at 30 days. No implant-related adverse events were reported. CONCLUSION: This study demonstrates the efficacy of steroid-releasing implants in improving outcomes of frontal sinus surgery. LEVEL OF EVIDENCE: 1b. Laryngoscope, 126:2659-2664, 2016. PMID- 27363724 TI - Determinants of self-esteem in early psychosis: The role of perceived social dominance. AB - Self-esteem plays a role in the formation and maintenance of symptoms and in the recovery from psychotic illness. This study examines the relative contribution of perceived social dominance and other known predictors in determining self-esteem in 102 individuals in an early intervention program for psychosis. Regression analysis demonstrated that scores on the Perceived Relational Evaluation Scale (PRES), depressed mood, social dominance, gender and positive symptoms significantly contributed to the prediction of scores on the Rosenberg Self esteem Scale (RSES), whereas self-stigma and negative symptoms did not. Our study suggests that low self-esteem in early psychosis can be understood in part as a reflection of low levels of perceived social value and status. PMID- 27363725 TI - Progressive Temporal Change in Serum SHBG, But Not in Serum Testosterone or Estradiol, Is Associated With Bone Loss and Incident Fractures in Older Men: The Concord Health and Ageing in Men Project. AB - This study aimed to examine progressive temporal relationships between changes in major reproductive hormones across three waves of a cohort study of older men and (1) changes in bone mineral density (BMD) and (2) incident fractures (any, hip or non-vertebral) over an average of 6 years of follow-up. The CHAMP cohort of men aged 70 years and older were assessed at baseline (2005 to 2007, n = 1705), 2 year follow-up (n = 1367), and 5-year follow-up (n = 958). Serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) (by liquid chromatography-tandem mass spectrometry [LC-MS/MS]), and sex hormone-binding globulin (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) (by immunoassay) were measured at all time-points, whereas free testosterone (cFT) was calculated using a well-validated formula. Hip BMD was measured by dual energy X-ray absorptiometry (DXA) at all three time-points, and fracture data were verified radiographically. Statistical modeling was done using general estimating equations (GEEs). For total hip BMD, univariable analyses revealed inverse associations with temporal changes in serum SHBG, FSH, and LH and positive associations for serum E1 and cFT across the three time-points. In models adjusted for multiple covariables, serum SHBG (beta = -0.029), FSH (beta = -0.065), LH (beta = -0.049), E1 (beta = 0.019), and cFT (beta = 0.033) remained significantly associated with hip BMD. However for femoral neck BMD, only FSH (beta = -0.048) and LH (beta = -0.036) remained associated in multivariable adjusted models. Temporal change in serum SHBG, but not T, E2, or other hormonal variables, was significantly associated with any, nonvertebral or hip fracture incidence in univariable analyses. In multivariable-adjusted models, temporal increase in serum SHBG over time remained associated with any fracture (beta = 0.060) and hip fracture (beta = 0.041) incidence, but not nonvertebral fracture incidence. These data indicate that a progressive increase in circulating SHBG over time predicts bone loss and fracture risk in older men. Further studies are warranted to further characterize changes in circulating SHBG as a mechanism and/or biomarker of bone health during male ageing. (c) 2016 American Society for Bone and Mineral Research. PMID- 27363726 TI - Classification of genetic variants in genes associated with Lynch syndrome using a clinical history weighting algorithm. AB - BACKGROUND: Lynch syndrome is a hereditary cancer syndrome associated with high risks of colorectal and endometrial cancer that is caused by pathogenic variants in the mismatch repair genes (MLH1, MSH2, MSH6, PMS2, EPCAM). Accurate classification of variants identified in these genes as pathogenic or benign enables informed medical management decisions. Previously, we developed a clinical History Weighting Algorithm (HWA) for the classification of variants of uncertain significance (VUSs) in BRCA1 and BRCA2. The BRCA1/2 HWA is based on the premise that pathogenic variants in these genes will be identified more often in individuals with strong personal and/or family histories of breast and/or ovarian cancer, while the identification of benign variants should be independent of cancer history. Here we report the development of a similar HWA to allow for classification of VUSs in genes associated with Lynch syndrome using data collected through both syndrome-specific and pan-cancer panel testing. METHODS: Upon completion of algorithm development, the HWA was tested using simulated variants constructed from 79,214 probands, as well as 379 true variants. Positive (PPV) and negative predictive values (NPV) were calculated on a per gene basis. RESULTS: 25,500 pathogenic and 50,500 benign simulated variants were analyzed using the HWA and the PPVs and NPVs for each gene were greater than 0.997 and 0.999, respectively. The HWA was also evaluated using 100 trials for each of the 379 true variants. PPVs of >0.998 and NPVs of >0.999 were obtained for all genes. CONCLUSIONS: We have developed and implemented a HWA to aid in the classification of VUSs in genes associated with Lynch syndrome. The work presented here demonstrates that this HWA is able to classify MLH1, MSH2, and MSH6 VUSs as either benign or pathogenic with high accuracy. PMID- 27363728 TI - The steady-state assumption in oscillating and growing systems. AB - The steady-state assumption, which states that the production and consumption of metabolites inside the cell are balanced, is one of the key aspects that makes an efficient analysis of genome-scale metabolic networks possible. It can be motivated from two different perspectives. In the time-scales perspective, we use the fact that metabolism is much faster than other cellular processes such as gene expression. Hence, the steady-state assumption is derived as a quasi-steady state approximation of the metabolism that adapts to the changing cellular conditions. In this article we focus on the second perspective, stating that on the long run no metabolite can accumulate or deplete. In contrast to the first perspective it is not immediately clear how this perspective can be captured mathematically and what assumptions are required to obtain the steady-state condition. By presenting a mathematical framework based on the second perspective we demonstrate that the assumption of steady-state also applies to oscillating and growing systems without requiring quasi-steady-state at any time point. However, we also show that the average concentrations may not be compatible with the average fluxes. In summary, we establish a mathematical foundation for the steady-state assumption for long time periods that justifies its successful use in many applications. Furthermore, this mathematical foundation also pinpoints unintuitive effects in the integration of metabolite concentrations using nonlinear constraints into steady-state models for long time periods. PMID- 27363727 TI - Site-specific recombinatorics: in situ cellular barcoding with the Cre Lox system. AB - BACKGROUND: Cellular barcoding is a recently developed biotechnology tool that enables the familial identification of progeny of individual cells in vivo. In immunology, it has been used to track the burst-sizes of multiple distinct responding T cells over several adaptive immune responses. In the study of hematopoiesis, it revealed fate heterogeneity amongst phenotypically identical multipotent cells. Most existing approaches rely on ex vivo viral transduction of cells with barcodes followed by adoptive transfer into an animal, which works well for some systems, but precludes barcoding cells in their native environment such as those inside solid tissues. RESULTS: With a view to overcoming this limitation, we propose a new design for a genetic barcoding construct based on the Cre Lox system that induces randomly created stable barcodes in cells in situ by exploiting inherent sequence distance constraints during site-specific recombination. We identify the cassette whose provably maximal code diversity is several orders of magnitude higher than what is attainable with previously considered Cre Lox barcoding approaches, exceeding the number of lymphocytes or hematopoietic progenitor cells in mice. CONCLUSIONS: Its high diversity and in situ applicability, make the proposed Cre Lox based tagging system suitable for whole tissue or even whole animal barcoding. Moreover, it can be built using established technology. PMID- 27363729 TI - Diabetes may affect the expression of matrix metalloproteinases and their inhibitors more than smoking in chronic periodontitis. AB - BACKGROUND AND OBJECTIVE: No previous study has directly compared the levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) between smokers and individuals with diabetes mellitus (DM) with periodontitis. Therefore, the aim of this study was to evaluate the gene expression of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 in tissues with chronic periodontitis (ChP) of smokers and individuals with type 2 DM. MATERIAL AND METHODS: Gingival biopsies were harvested from: non-smokers and non-diabetic individuals with ChP (n = 18) (ChP group); non-diabetic smokers (>= 10 cigarettes per day for at least the past 5 years) with ChP (n = 18) (SChP group); non smoking individuals with type 2 diabetes (glycated hemoglobin levels >= 7.5%) and ChP (n = 18) (DMChP group). The tissue levels of mRNA of MMP-1, MMP-2, MMP-8, MMP 9, TIMP-1 and TIMP-2 were evaluated by quantitative real-time polymerase chain reaction. RESULTS: The MMP-8 expression was the lowest in the ChP group (p < 0.05). The DMChP group presented increased mRNA levels of MMP-2 and MMP-9, when compared to the SChP group (p < 0.05). MMP-1 expression and the MMP-1/TIMP-1, MMP 2/TIMP-1, MMP-8/TIMP-1, MMP-9/TIMP-1, MMP-1/TIMP-2 and MMP-2/TIMP-2 ratios were higher in the DMChP group than in the ChP and SChP groups (p < 0.05). The DMChP group presented lower mRNA levels of TIMP-1 than the ChP group (p < 0.05). The MMP-8/TIMP-2 ratio was the highest in the SChP group (p < 0.05). CONCLUSION: Uncontrolled type 2 DM upregulates the ratio of MMP/TIMPs in sites with ChP more than smoking, which may contribute to a greater extracellular matrix degradation and periodontal breakdown in DM-related periodontitis. PMID- 27363730 TI - Trends in diabetes incidence from 1992 to 2015 and projections for 2024: A Portuguese General Practitioner's Network study. AB - BACKGROUND: Diabetes is known as a major cause of morbidity and mortality worldwide. Portugal is known as the European country with the highest prevalence of this disease. While diabetes prevalence data is updated annually in Portugal, the General Practitioner's (GP) Sentinel Network represents the only data source on diabetes incidence. This study describes the trends in Diabetes incidence, between 1992 and 2015, and estimate projections for the future incidence rates in Portugal until 2024. METHODS: An ecological time-series study was conducted using data from GP Sentinel Network between 1992 and 2015. Family doctors reported all new cases of Diabetes in their patients' lists. Annual trends were estimated through Poisson regression models as well as the future incidence rates (until 2024), sex and age group stratified. Incidence rate projections were adjusted to the distribution of the resident Portuguese population given Statistics Portugal projections. RESULTS: The average increase in Diabetes incidence rate was in total 4.29% (CI95% 3.80-4.80) per year under study. Until 1998-2000, the annual incidence rate was higher in women, and from 1998-2000 to 2013-2015 turn out to be higher in men. The incidence rate projected for 2022-2024 was 972.77/10(5) inhabitants in total, and 846.74/10(5) and 1114.42/10(5), respectively, in women and men. CONCLUSIONS: This is the first study in Portugal to estimate diabetes incidence rate projections. The disturbing reported projections seem realistic if things continue as in the past. Actually, effective public health policies will need to be undertaken to minimize this alarming future scenario. PMID- 27363731 TI - Delayed hypersensitivity reaction to loperamide: An intriguing case report with positive challenge test. PMID- 27363732 TI - Predicting peak oxygen uptake from submaximal exercise after spinal cord injury. AB - The purpose of this study was to determine the validity of the 6-min arm ergometry test (6MAT) in predicting peak oxygen consumption (VO2peak) in individuals with chronic spinal cord injury (SCI). Fifty-two individuals with chronic SCI (age, 38 +/- 10 years; American Spinal Injury Association Impairment Scale (AIS), A-D; neurological level of injury (NLI), C1-L2; years post-injury (YPI), 13 +/- 10 years) completed an incremental arm ergometry VO2peak test and a submaximal 6MAT. Oxygen consumption (VO2) data from both tests were used to create a predictive equation with regression analysis. Subsequently, a cross validation group comprising an additional 10 individuals with SCI (age, 39 +/- 13 years; AIS, A-D; NLI, C3-L3; YPI, 9 +/- 9 years) were used to determine the predictive power of the equation. All participants were able to complete both the VO2peak and 6MAT assessments. Regression analysis yielded the following equation to predict VO2peak from end-stage 6MAT VO2: VO2peak (mL.kg(-1).min(-1)) = 1.501(6MAT VO2) - 0.940. Correlation between measured and predicted VO2peak was excellent (r = 0.89). No significant difference was found between measured (17.41 +/- 7.44 mL.kg(-1).min(-1)) and predicted (17.42 +/- 6.61 mL.kg(-1).min(-1)) VO2peak (p = 0.97). When cross-validated with a sample of 10 individuals with SCI, correlation between measured and predicted VO2peak remained high (r = 0.89), with no differences between measured (18.81 +/- 8.35 mL.kg(-1).min(-1)) and predicted (18.73 +/- 7.27 mL.kg(-1).min(-1)) VO2peak (p = 0.75). Results suggest that 6MAT VO2 can be used to predict VO2peak among individuals with chronic SCI. The 6MAT should be used as a clinical tool for assessing aerobic capacity when peak exercise testing is not feasible. PMID- 27363733 TI - Lactobacillus helveticus Lafti L10 supplementation reduces respiratory infection duration in a cohort of elite athletes: a randomized, double-blind, placebo controlled trial. AB - A randomized, double-blind, placebo-controlled study was conducted to evaluate if Lactobacillus helveticus Lafti L10 (Lallemand Health Solutions, Montreal, Que., Canada) supplementation during 14 weeks in winter can influence the duration, severity, and incidence of upper respiratory tract illness (URTI), as well as to monitor different immune parameters in the population of elite athletes. Before and after the treatment, cardiopulmonary testing and self-rated state of moods evaluation (by Profile of Mood States questionnaire) were performed and blood samples were collected. Thirty-nine elite athletes were randomized either to the placebo (n = 19) or the probiotic (n = 20) group. The probiotic group received L. helveticus Lafti L10, 2 * 10(10) Colony Forming Units. Lafti L10 significantly shortened the URTI episode duration (7.25 +/- 2.90 vs. 10.64 +/- 4.67 days, p = 0.047) and decreased the number of symptoms in the probiotic group (4.92 +/- 1.96 vs. 6.91 +/- 1.22, p = 0.035). Severity and incidence of URTI did not differ between the treatments. There were no significant changes in leukocyte subpopulation abundance, transforming growth factor-beta serum levels, level of interleukin-10 secreted from peptidoglican stimulated peripheral blood mononuclear cells (PBMCs), interferon-gamma level secreted from concanavalin A stimulated PBMCs or viability/proliferation of PBMCs upon antigen stimulation. Group effect for CD4+/CD8+ ratio was significant (F[1,37] = 6.99, p = 0.020, eta(2) = 0.350); this difference was not significant at baseline, but was evident after 14 weeks (p = 0.02). A significant interaction effect was noted for self rated sense of vigor (F[1,37] = 11.76, p = 0.009, eta(2) = 0.595). Self-rated sense of vigor increased in the probiotic group (18.5 +/- 4.1 vs. 21.0 +/- 2.6, p = 0.012). Probiotic strain Lafti L10 can be a beneficial nutritional supplement for the reduction of URTI length in elite athletes. PMID- 27363734 TI - Efficacy of Low-Level Laser Therapy in Relieving Nipple Pain in Breastfeeding Women: A Triple-Blind, Randomized, Controlled Trial. AB - Pain accruing from nipple lesions caused by inadequate latching by the baby is a common complaint among breastfeeding women and an important obstacle to successful breastfeeding. Nipple pain occurs during the first days after delivery and is considered one of the main causes for early weaning. To investigate the efficacy of low-level laser therapy as a treatment for nipple pain due to breastfeeding. A triple-blind, randomized, clinical study. A university affiliated hospital in Sao Paulo, Brazil. Fifty-nine women with nipple lesions at the time of their admission. Thirty women (intervention group) received three sessions of laser therapy (InGaAIP laser, 660 nanometer, 40 milliwatts of power, 5 Joules per square centimeter of energy density for 5 seconds each, total energy = 0.6 Joules) in the region of the nipples at three different points in time (0 hour, 24 hours, and 48 hours after diagnosis of nipple lesion). Twenty-nine women with similar clinical conditions were randomly assigned to the control group. Self-reported pain was recorded before and after laser therapy using a visual analogue scale. The intervention group experienced a decrease of 2.0 centimeters in intensity of pain (p = .016) 24 hours after the first intervention and also presented lower levels of pain compared with the control group. Low-level laser therapy was considered effective for treating nipple lesions in breastfeeding women with pain, providing relief and prolonging exclusive breastfeeding. More clinical trials with different laser dosimetry and parameters are necessary to optimize laser therapy protocols for breastfeeding women. PMID- 27363735 TI - Separation of mono- and di-PEGylate of exenatide and resolution of positional isomers of mono-PEGylates by preparative ion exchange chromatography. AB - Exenatide is a synthetic version of the 39-mer peptide of Exendin-4, which is an FDA-approved therapeutic against Type II diabetes mellitus. However, exenatide has a very short in-serum half-life and PEGylation have been performed to improve its in-serum stability. PEGylation often yields multivalent binding to non specific residues, and the desired species should be carefully separated by chromatographies. In this study, we first devised an aqueous-phase, two-step PEGylation process. This consists of thiolation of Lys 12 and 27 residues followed by attachment of PEG-maleimide (10kD) to thiol groups. This process yields various species: mono-PEGylates with positional isomers, di-PEGylate, and other higher MW substances. A prep-grade cationic exchange chromatography (HiTrap SP) at pH 3.0 partially separated mono- and di-PEGylates based on the molar ratio of conjugated PEG and peptide and thus molecular weight of the conjugates. To further investigate the chromatographic separation of positional isomers of mono PEGylates, we prepared two kinds of exenatide analogs by point mutation; K12C and K27C. Each analog was mono-PEGylated with very high yield (>95%). When a mixture of the two positional isomers of mono-PEGylates was applied to HiTrap SP chromatography, K12C-PEGylate and K27C-PEGylate eluted separately at 0.22M and 0.33M NaCl, respectively. When the proportions of acid and its conjugate base of the amino acid residues adjacent to the PEGylation site at pH 3.0 were analyzed, K27C-PEGylate shows stronger positive charge than K12C-PEGylate, and we propose the residence time difference between the two mono-PEGylates could be due to the charge difference. ELISA result shows that the immuno-binding activity of both analogs and their mono-PEGylates are well maintained. Furthermore, both mono PEGylates of the analogs show higher than 50-fold improved anti-trypsin stability. We expect that mono-PEGylates of the exenatide analogs are alternatives to the conventional C40-PEG. PMID- 27363736 TI - Simultaneous determination of rare earth elements in ore and anti-corrosion coating samples using a portable capillary electrophoresis instrument with contactless conductivity detection. AB - The employment of an in-house-made capillary electrophoresis (CE) instrument with capacitively coupled contactless conductivity detection (C(4)D) as a simple and inexpensive solution for simultaneous determination of many rare earth elements (REEs) in ore samples from Vietnam, as well as in anti-corrosion coating samples is reported. 14 REEs (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu) were determined using an electrolyte composed of 20mM arginine and 10mM alpha hydroxyisobutyric acid adjusted to pH 4.2 with acetic acid. The best detection limit achieved was 0.24mg/L using the developed CE-C(4)D method. Good agreement between results from CE-C(4)D and the confirmation method (ICP-MS) was achieved, with a coefficient of determination (r(2)) for the two pairs of data of 0.998. PMID- 27363737 TI - Quantitative real-time PCR assays for detection and type-specific identification of the endemic species C human adenoviruses. AB - Human adenoviruses (HAdVs) are medically important respiratory pathogens. Among the 7 recognized species (A-G), species C HAdVs (serotypes 1, 2, 5 and 6) are globally endemic and infect most people early in life. Species C HAdV infections are most often subclinical or mild and can lead to persistent shedding from the gastrointestinal and upper respiratory tracts. They can also cause severe disseminated disease in newborn and immunocompromised persons, where rapid and quantitative detection and identification of the virus would help guide therapeutic intervention. To this end, we developed quantitative type-specific real-time PCR (qPCR) assays for HAdV-1, -2, -5 and -6 targeting the HAdV hexon gene. All type-specific qPCR assays reproducibly detected as few as 5 copies/reaction of quantified hexon recombinant plasmids with a linear dynamic range of 8 log units (5-5*107 copies). No non-specific amplifications were observed with concentrated nucleic acid from other HAdV types or other common respiratory pathogens. Of 199 previously typed HAdV field isolates and positive clinical specimens, all were detected and correctly identified to type by the qPCR assays; 10 samples had 2 HAdV types and 1 sample had 3 types identified which were confirmed by amplicon sequencing. The species C HAdV qPCR assays permit rapid, sensitive, specific and quantitative detection and identification of four recognized endemic HAdVs. Together with our previously developed qPCR assays for the epidemic respiratory HAdVs, these assays provide a convenient alternative to classical typing methods. PMID- 27363738 TI - Donation after circulatory death in pediatric patients: Current utilization in the United States. PMID- 27363741 TI - Information provision in post-reproductive healthcare. PMID- 27363739 TI - The upper respiratory tract microbiome and its potential role in bovine respiratory disease and otitis media. AB - The upper respiratory tract (URT) hosts a complex microbial community of commensal microorganisms and potential pathogens. Analyzing the composition and nature of the healthy URT microbiota and how it changes over time will contribute to a better understanding of the pathogenesis of pneumonia and otitis. A longitudinal study was conducted including 174 Holstein calves that were divided in four groups: healthy calves, calves diagnosed with pneumonia, otitis or both diseases. Deep pharyngeal swabs were collected on days 3, 14, 28, and 35 of life, and next-generation sequencing of the 16S rRNA gene as well as quantitative PCR was performed. The URT of Holstein dairy calves aged 3 to 35 days revealed to host a highly diverse bacterial community. The relative abundances of the bacterial genera Mannheimia, Moraxella, and Mycoplasma were significantly higher in diseased versus healthy animals, and the total bacterial load of newborn calves at day 3 was higher for animals that developed pneumonia than for healthy animals. Our results corroborate the existing knowledge that species of Mannheimia and Mycoplasma are important pathogens in pneumonia and otitis. Furthermore, they suggest that species of Moraxella can potentially cause the same disorders (pneumonia and otitis), and that high neonatal bacterial load is a key contributor to the development of pneumonia. PMID- 27363740 TI - Determination of CSF 5-methyltetrahydrofolate in children and its application for defects of folate transport and metabolism. AB - OBJECTIVE: To describe an assay of 5-methyltetrahydrofolate (5MTHF) in the cerebrospinal fluid (CSF) of children, to determine reference values, and to report the clinical significance of this assay in metabolic disorders affecting folate transport and metabolism. METHODS: CSF 5MTHF was determined by high performance liquid chromatography with fluorescent detection in pediatric patients including one with FOLR1 gene mutation and one with methylenetetrahydrofolate reductase (MTHFR) deficiency. CSF total folate was measured using an automated analyzer. RESULTS: 5MTHF and total folate were determined in 188 and 93 CSF samples, respectively. CSF 5MTHF was high throughout the first six months of life and subsequently declined with age. Reference values of CSF 5MTHF and total folate were determined from 162 and 82 samples, respectively. The patient with FOLR1 gene mutation had extremely low CSF 5MTHF and total folate, though these values normalized after folinic acid supplementation. The patient with MTHFR deficiency had extremely low 5MTHF and moderately low total folate; these values were not associated and showed no significant change after folic acid supplementation. CONCLUSIONS: This 5MTHF assay is simple, rapid, sensitive, reliable, and cost-effective. It will aid in the diagnosis and therapeutic monitoring of metabolic disorders affecting folate transport and metabolism. PMID- 27363743 TI - Diagnosis of perimenopause and menopause (Section 5). PMID- 27363744 TI - Information and advice (Section 7). PMID- 27363745 TI - Managing short-term menopausal symptoms (Section 8). PMID- 27363746 TI - Alternatives to hormone replacement therapy (HRT) (Sections 1 and 8). PMID- 27363747 TI - Review and referral (Section 9). PMID- 27363748 TI - Starting and stopping HRT (Section 10). PMID- 27363749 TI - Long-term benefits and risks of HRT (Section 11): Venous thromboembolism. PMID- 27363750 TI - Long-term benefits and risks of HRT (Section 11): Cardiovascular disease. PMID- 27363751 TI - Long-term benefits and risks of HRT (Section 11): Type 2 Diabetes. PMID- 27363752 TI - Long-term benefits and risks of HRT (Section 11): Breast cancer. PMID- 27363753 TI - Long-term benefits and risks of HRT (Section 11): Osteoporosis. PMID- 27363754 TI - Long-term benefits and risks of HRT (Section 11): Dementia. PMID- 27363755 TI - Long-term benefits and risks of HRT (Section 11): Loss of muscle mass (Sarcopenia). PMID- 27363756 TI - Practice observed. PMID- 27363757 TI - Patient-reported outcome of surgical treatment for lumbar spinal epidural lipomatosis. AB - BACKGROUND CONTEXT: Spinal epidural lipomatosis (SEL) is a rare condition characterized by an excessive accumulation of fat tissue in the spinal canal that can have a compressive effect, leading to clinical symptoms. This condition has a distinct pathology from spinal stenosis associated with degeneration of the intervertebral discs, ligaments, and facet joints. Several different conservative and surgical treatment strategies have been proposed for SEL, but its treatment remains controversial. There is a lack of evidence documenting the success of surgical decompression in SEL, and no previous studies have reported the postoperative outcome from the patient's perspective. PURPOSE: The aim of the present study was to evaluate patient-rated outcome after surgical decompression in SEL. STUDY DESIGN: A retrospective analysis of prospectively collected data was carried out. PATIENT SAMPLE: A total of 22 patients (19 males; age: 68.2+/ 9.9 years) who had undergone spine surgery for SEL were identified from our local Spine Surgery Outcomes Database, which includes a total of 10,028 spine surgeries recorded between 2005 and 2012. Inclusion criteria were epidural lipomatosis confirmed by preoperative magnetic resonance imaging (MRI) scans and subsequent decompression surgery without spinal fusion. OUTCOME MEASURES: The Core Outcome Measures Index (COMI) was used to assess patient-rated outcome. The COMI includes the domains pain (separate 0-10 scales for back and leg pain), back-specific function, symptom-specific well-being, general quality of life (QOL), work disability, and social disability. METHODS: The questionnaires were completed preoperatively and at 3, 12, and 24 months postoperatively. Surgical data were retrieved from the patient charts and from our local Spine Surgery Outcomes Database, which we operate in connection with the International Spine Tango Registry. Differences between pre- and postoperative scores were analyzed using paired t tests and repeated measures analysis of variance. RESULTS: At 3-months follow-up, the COMI score and scores for leg pain and back pain had improved significantly compared with their preoperative values (p<.005). The mean decrease in COMI score after 3 months was 2.6+/-2.4 (range: -1.3 to 6.5) points: from 7.5+/-1.7 (range: 3.5-10) to 4.9+/-2.5 (range: 0.5-9.6). A total of 11 patients (50%) had an improvement of the COMI of more than the minimal clinically important change (MCIC) score of 2.2 points. The mean decrease in leg pain after 3 months was 2.4+/-3.5 (-5 to 10) points. Overall, 17 patients (77.3%) reported a reduced leg pain, 12 (54.6%) of whom by at least the MCIC score of 2 points. The significant reductions from baseline in COMI and leg and back pain scores were retained up to 2 years postoperatively (p<.02). The general QOL item of the COMI improved significantly after surgery (p<.0001). Over 80% of the cohort rated their preoperative QOL as bad (n=13) or very bad (n=5), whereas 3 months after surgery, only 7 patients rated their QOL as bad, and one as very bad (36%). CONCLUSIONS: The present study is the first to demonstrate that surgical decompression is associated with a statistically significant improvement in patient-rated outcome scores in patients with symptomatic SEL, with a clinically relevant change occurring in approximately half of them. Surgical decompression hence represents a reasonable treatment option for SEL, although the reason behind the less good response in some patients needs further investigation. PMID- 27363758 TI - Pulsatile Support Mode of BJUT-II Ventricular Assist Device (VAD) has Better Hemodynamic Effects on the Aorta than Constant Speed Mode: A Primary Numerical Study. AB - BACKGROUND BJUT-II VAD is a novel left ventricular assist device (LVADs), directly implanted into the ascending aorta. The pulsatile support mode is proposed to achieve better unloading performance than constant speed mode. However, the hemodynamic effects of this support mode on the aorta are still unclear. The aim of this study was to clarify the hemodynamic effects BJUT-II VAD under pulsatile support mode on the aorta. MATERIAL AND METHODS Computational fluid dynamics (CFD) studies, based on a patient-specific aortic geometric model, were conducted. Wall shear stress (WSS), averaged WSS (avWSS), oscillatory shear index (OSI), and averaged helicity density (Ha) were calculated to compare the differences in hemodynamic effects between pulsatile support mode and constant speed mode. RESULTS The results show that avWSS under pulsatile support mode is significantly higher than that under constant speed mode (0.955Pa vs. 0.675Pa). Similarly, the OSI value under pulsatile mode is higher than that under constant speed mode (0.104 vs. 0.057). In addition, Ha under pulsatile mode for all selected cross-sections is larger than that under constant mode. CONCLUSIONS BJUT II VAD, under pulsatile control mode, may prevent atherosclerosis lesions and aortic remodeling. The precise effects of pulsatile support mode on atherosclerosis and aortic remodeling need to be further studied in animal experiments. PMID- 27363759 TI - Incorporating Minimally Invasive Procedures into an Aesthetic Surgery Practice. AB - Minimally invasive procedures in an aesthetic practice have grown over the past decade. Plastic surgery practices are embracing the incorporation of injectables and lasers as adjuncts to their surgical procedures. The use of botulinum toxin, hyaluronic acid fillers, and lasers has made a significant impact on the authors' practice. The authors describe the important considerations, consultation goals, and procedural steps with injectables and fillers. The novel use of deoxycholic acid injections is also described. The authors strongly think that as options continue to expand, plastic surgeons will benefit from taking an active role in adopting these new innovations. PMID- 27363760 TI - Overview of Botulinum Toxins for Aesthetic Uses. AB - Botulinum toxin type A (BTA) can be used for facial aesthetics. The 3 currently available BTA types include onabotulinumtoxinA (Botox; Botox Cosmetic, Allergan, Irvine, CA), abobotulinumtoxinA (Dysport; Ipsen, Ltd, Berkshire, UK), and incobotulinumtoxinA (Xeomin; Merz Pharmaceuticals, Frankfurt, Germany). The mechanism of action and clinical uses for treatment of dynamic lines of the forehead, brow, glabella, lateral orbit, nose, and lips are presented, as well as treatment of masseter hypertrophy, platysmal bands, and improvements of the perioral region. Specific BTA injection sites and suggested doses are presented. PMID- 27363761 TI - Fat, Stem Cells, and Platelet-Rich Plasma. AB - The ideal filler for aesthetic surgery is inexpensive and easy to obtain, natural in appearance and texture, immunologically compatible, and long lasting without risk of infection. By most metrics, autologous fat grafts meet these criteria perfectly. Although facial fat grafting is now a commonly accepted surgical procedure, there has been a wave of activity applying stem cells and platelet rich plasma (PRP) therapies to aesthetic practice. This article addresses technical considerations in the use of autologous fat transfer for facial rejuvenation, and also explores the current evidence for these stem cell and PRP therapies in aesthetic practice. PMID- 27363762 TI - Hyaluronic Acid Fillers: Science and Clinical Uses. AB - Hyaluronic acid soft tissue fillers include a range of products (Juvederm Ultra, Juvederm Ultra Plus, Voluma, Restylane Silk, Restylane, Restylane Lyft, and Belotero Balance) that are used commonly for facial rejuvenation and enhancement of facial features. Although these products are similar in many ways, they are not interchangeable and have unique characteristics that need to be considered. Injection sites and techniques for facial rejuvenation are discussed. PMID- 27363763 TI - Synthetic Fillers for Facial Rejuvenation. AB - Soft tissue filler procedures have increased dramatically in popularity in the United States. Synthetic fillers such as calcium hydroxyapatite (CaHA), polymethyl methacrylate (PMMA), and poly-l-lactic acid (PLLA), and silicone provide initial volume replacement but have an additional biostimulatory effect to supplement facial volumization. Indications include human immunodeficiency virus lipoatrophy and nasolabial folds for CaHA and PLLA and atrophic acne scars for PMMA. Most clinical use of these synthetic fillers is in an off-label fashion. Beyond the proper choice of a synthetic filler, careful consideration of dilution, injection method, and postprocedural care allows for successful and consistent results. PMID- 27363764 TI - Basics of Lasers: History, Physics, and Clinical Applications. AB - Lasers are increasingly used by plastic surgeons to address issues such as wrinkles and textural changes, skin laxity, hyperpigmentation, vascularity, and excess fat accumulation. A fundamental understanding of the underlying science and physics of laser technology is important for the safe and efficacious use of laser in medical settings. The purpose of this article was to give clinicians with limited exposure to lasers a basic understanding of the underlying science. In that manner, they can confidently make appropriate decisions as to the best device to use on a patient (or the best device to purchase for a practice). PMID- 27363765 TI - Laser Resurfacing: Full Field and Fractional. AB - Laser resurfacing is a very popular procedure worldwide. Full field and fractional lasers are used in many aesthetic practices. There have been significant advances in laser resurfacing in the past few years, which make patient treatments more efficacious and with less downtime. Erbium and carbon dioxide and ablative, nonablative, and hybrid fractional lasers are all extremely effective and popular tools that have a place in plastic surgery and dermatology offices. PMID- 27363766 TI - Subsurface Laser and Radiofrequency for Face and Body Rejuvenation. AB - Minimally invasive devices are a departure from standard laser therapies, because energy is delivered directly below the skin through a 1-mm incision. Lasers can affect such tissues as fat for enhanced disruption, coagulation of small blood vessels, and skin tightening at the right temperatures. Minimally invasive radiofrequency devices can tighten skin but can also improve neck muscle laxity. These devices can achieve results not possible with traditional external devices and, because the skin is not penetrated with energy, a much improved healing profile is seen as well. PMID- 27363767 TI - Intense Pulsed Light Therapy for Skin Rejuvenation. AB - Intense pulsed light (IPL), also known as pulsed light and broad band light, is a nonlaser light source used to treat a variety of vascular and pigmented lesions, photo damage, active acne, and unwanted hair. Current IPL systems are much improved from older-generation devices with better calibration, integrated cooling, and improved tuning. These devices are extremely popular because of their versatility and are often the first devices recommended and purchased in many offices. PMID- 27363768 TI - Low Level Light Therapy with Light-Emitting Diodes for the Aging Face. AB - Low level light therapy (LLLT) with light-emitting diodes (LEDs) is emerging from the mists of black magic as a solid medico-scientific modality, with a substantial buildup of corroborative bodies of evidence for its efficacy and elucidation of the modes of action. Reports are appearing from many different specialties; however, of particular interest to plastic surgeons treating the aging face is the proven action of LED-LLLT on skin cells in both the epidermis and dermis and enhanced blood flow. Thus, LED-LLLT is a safe and effective stand alone therapy for patients who are prepared to wait until the final effect is perceived. PMID- 27363769 TI - Radiofrequency Physics for Minimally Invasive Aesthetic Surgery. AB - Radiofrequency energy has a wide range of medical applications, including noninvasive treatment of wrinkles and body contouring. This technology works by differential heating of skin and soft tissue layers causing dermal remodeling or adipolysis, ultimately leading to observable effects. This article reviews the physics of radiofrequency as applied clinically. PMID- 27363770 TI - Aesthetic Applications of Radiofrequency Devices. AB - Radiofrequency (RF)-based devices are used to improve face and neck laxity, a major feature of aging that until recently could only be addressed with surgery. Although these treatments are not meant to replace surgical procedures, patient satisfaction studies have been consistently high. For physicians offering these skin rejuvenation procedures, it is essential to have intimate knowledge of how the devices work, select appropriate candidates, set realistic expectations, and combine treatments to optimize outcomes. This article discusses the various noninvasive RF technologies currently in use and reviews pertinent clinical studies evaluating their efficacy and safety. PMID- 27363771 TI - Minimally Invasive Radiofrequency Devices. AB - This article reviews minimally invasive radiofrequency options for skin tightening, focusing on describing their mechanism of action and clinical profile in terms of safety and efficacy and presenting peer-reviewed articles associated with the specific technologies. Treatments offered by minimally invasive radiofrequency devices (fractional, microneedling, temperature-controlled) are increasing in popularity due to the dramatic effects they can have without requiring skin excision, downtime, or even extreme financial burden from the patient's perspective. Clinical applications thus far have yielded impressive results in treating signs of the aging face and neck, either as stand-alone or as postoperative maintenance treatments. PMID- 27363772 TI - Microfocused Ultrasound for Skin Tightening. AB - Microfocused ultrasound (MFU) generates tissue heating, which can be used for facial skin tightening as well as other areas of skin laxity. Unlike radiofrequency energy, MFU can penetrate deep into tissue without heating the superficial skin structures, allowing for higher treatment temperatures. Depending on patient factors and treatment protocols, 60% to 90% of patients can expect to see facial improvement 6 months after treatment. PMID- 27363773 TI - Mesotherapy, Microneedling, and Chemical Peels. AB - Mesotherapy, microneedling, and chemical peels are minimally invasive techniques used to combat facial aging. Chemical peeling is one of the oldest methods of facial rejuvenation. By using different chemicals in various combinations, strengths, and application techniques, plastic surgeons can tailor a patient's treatment for optimal, safe, and consistent results. Mesotherapy and microneedling have emerged in the plastic surgery literature with increasingly complex indications. Both techniques have increased in popularity although research into efficacy and long-term results is lagging. With a thorough understanding of patients and the modalities available, plastic surgeons can use the appropriate minimally invasive technique to provide patients with desired skin changes. PMID- 27363774 TI - Topical Products for the Aging Face. AB - This article focuses on nonprescription home-use topical treatment technologies for the aging face and is intended to serve as a guide for the core cosmeceutical technologies currently used and to help educate and assist the selection of topical antiaging products by the professional staff and their patients. Antiaging topical treatments for patient home use should be nonirritating, compatible with the patient skin type, effective, and complementary to surgical and minimally invasive office procedures, and aesthetically elegant. New topical antiaging technologies, formulated as monotherapy or as combinations with well known cosmeceuticals, should present adequate clinical studies to support their selection for use. PMID- 27363775 TI - Sun Protection: Current Management Strategies Addressing UV Exposure. AB - The use of sunscreen is essential for protection against photoaging and skin cancer. There is no global consensus on rating systems for sunscreens but it is essential to understand what makes a product broad-spectrum. In addition, physicians should have a general understanding that high-quality successful sunscreens should not only provide broad-spectrum ultraviolet A/B protection but should also be formulated so that they are easy to apply, are water resistant, and are photostable in order to increase user compliance. PMID- 27363776 TI - Minimally Invasive Procedures: Essential Tools for the Aesthetic Surgeon. PMID- 27363777 TI - Piezo-generator integrating a vertical array of GaN nanowires. AB - We demonstrate the first piezo-generator integrating a vertical array of GaN nanowires (NWs). We perform a systematic multi-scale analysis, going from single wire properties to macroscopic device fabrication and characterization, which allows us to establish for GaN NWs the relationship between the material properties and the piezo-generation, and to propose an efficient piezo-generator design. The piezo-conversion of individual MBE-grown p-doped GaN NWs in a dense array is assessed by atomic force microscopy (AFM) equipped with a Resiscope module yielding an average output voltage of 228 +/- 120 mV and a maximum value of 350 mV generated per NW. In the case of p-doped GaN NWs, the piezo-generation is achieved when a positive piezo-potential is created inside the nanostructures, i.e. when the NWs are submitted to compressive deformation. The understanding of the piezo-generation mechanism in our GaN NWs, gained from AFM analyses, is applied to design a piezo-generator operated under compressive strain. The device consists of NW arrays of several square millimeters in size embedded into spin-on glass with a Schottky contact for rectification and collection of piezo-generated carriers. The generator delivers a maximum power density of ~12.7 mW cm(-3). This value sets the new state of the art for piezo-generators based on GaN NWs and more generally on nitride NWs, and offers promising prospects for the use of GaN NWs as high-efficiency ultra-compact energy harvesters. PMID- 27363779 TI - Concluding remarks: Faraday Discussion on chemistry in the urban atmosphere. AB - This article summarises the Concluding remarks from the Faraday Discussion on Chemistry in the Urban Atmosphere. The following themes are addressed: (a) new results that inform our understanding of the evolving sources and composition of the urban atmosphere ("News"); (b) results that identify gaps in our understanding that necessitate further work ("Gaps"); PMID- 27363778 TI - Dynamin 1 isoform roles in a mouse model of severe childhood epileptic encephalopathy. AB - Dynamin 1 is a large neuron-specific GTPase involved in the endocytosis and recycling of pre-synaptic membranes and synaptic vesicles. Mutations in the gene encoding dynamin 1 (DNM1) underlie two epileptic encephalopathy syndromes, Lennox Gastaut Syndrome and Infantile Spasms. Mice homozygous for the Dnm1 "fitful" mutation, a non-synonymous coding variant in an alternatively spliced exon of Dnm1 (exon 10a; isoform designation: Dnm1a(Ftfl)) have an epileptic encephalopathy-like disorder including lethal early onset seizures, locomotor and neurosensory deficits. Although fitful heterozygotes have milder recurrent seizures later in life, suggesting an additive or semi-dominant mechanism, the molecular etiology must also consider the fact that Dnm1a(Ftfl) exerts a dominant negative effect on endocytosis in vitro. Another complication is that the fitful mutation induces alterations in the relative abundance of Dnm1 splice variants; mutants have a downregulation of Dnm1a and an upregulation of Dnm1b, changes which may contribute to the epileptic pathology. To examine whether Dnm1a loss of function, Dnm1a(Ftfl) dominance or compensation by Dnm1b is the most critical for severe seizures, we studied alternate isoform-specific mutant mice. Mice lacking Dnm1 exon 10a or Dnm1 exon 10b have neither spontaneous seizures nor other overt abnormalities, suggesting that in normal conditions the major role of each isoform is redundant. However, in the presence of Dnm1a(Ftfl) only exon 10a deleted mice experience severe seizures. These results reveal functional differences between Dnm1a and Dnm1b isoforms in the presence of a challenge, i.e. toxic Dnm1(Ftfl), while reinforcing its effect explicitly in this model of severe pediatric epilepsy. PMID- 27363780 TI - The interplay of aggregation, fibrillization and gelation of an unexpected low molecular weight gelator: glycylalanylglycine in ethanol/water. AB - Hydrogels formed by polypeptides could be much-favored tools for drug delivery because their main ingredients are generally biodegradable. However, the gelation of peptides in aqueous solution generally requires a minimal length of the peptide as well as distinct sequences of hydrophilic and hydrophobic residues. The aggregation of short peptides like tripeptides, which are relatively cheap and offer a high degree of biodegradability, are generally thought to require a high hydrophobicity of their residues. We found that contrary to this expectation cationic glycylalanylglycine in 55 mol% ethanol/45 mol% water forms a gel below a melting temperature of ca. 36 degrees C. A pure hydrogel state can be obtained after allowing the ethanol component to evaporate. The gel phase consists of crystalline fibrils of several 100 MUm, which form a sample-spanning network. Rheological data reveal a soft elastic solid gel. We investigated the kinetics of the various processes that lead to the final gel state of the ternary mixture by a unique combination of UV circular dichroism, infrared, vibrational circular dichroism (VCD) and rheological measurements. A mathematical analysis of our data show that gelation is preceded by the formation of peptide beta-sheet like tapes or ribbons, which give rise to a significant enhancement of the amide I' VCD signal, and the subsequent formation of rather thick and long fibrils. The VCD signals indicate that the tapes exhibit a right-handed helicity at temperatures above 16 degrees C and a left-handed helicity below. The tapes'/ribbons' helicity change occurs at a temperature where the UVCD data reflect a relatively long nucleation process. The kinetics of gel formation probed by the storage and loss moduli are composed of a fast process that follows tape/ribbon/fibril formation and is clearly identifiable in a movie that shows the gelation process and a slow process that causes an additional gel stabilization. The rheological data indicate that left-handed fibrils observed at low temperatures form a more solid-like structure than their right-handed counterparts formed at higher temperatures. Taken together our data reveal GAG as an unexpected gelator, the formation of which is underlied by a set of distinguishable kinetic processes. PMID- 27363781 TI - microRNA expression profile in human coronary smooth muscle cell-derived microparticles is a source of biomarkers. AB - INTRODUCTION: microRNA (miRNA) expression profile of extracellular vesicles is a potential tool for clinical practice. Despite the key role of vascular smooth muscle cells (VSMC) in cardiovascular pathology, there is limited information about the presence of miRNAs in microparticles secreted by this cell type, including human coronary artery smooth muscle cells (HCASMC). Here, we tested whether HCASMC-derived microparticles contain miRNAs and the value of these miRNAs as biomarkers. METHODS: HCASMC and explants from atherosclerotic or non atherosclerotic areas were obtained from coronary arteries of patients undergoing heart transplant. Plasma samples were collected from: normocholesterolemic controls (N=12) and familial hypercholesterolemia (FH) patients (N=12). Both groups were strictly matched for age, sex and cardiovascular risk factors. Microparticle (0.1-1MUm) isolation and characterization was performed using standard techniques. VSMC-enriched miRNAs expression (miR-21-5p, -143-3p, -145 5p, -221-3p and -222-3p) was analyzed using RT-qPCR. RESULTS: Total RNA isolated from HCASMC-derived microparticles contained small RNAs, including VSMC-enriched miRNAs. Exposition of HCASMC to pathophysiological conditions, such as hypercholesterolemia, induced a decrease in the expression level of miR-143-3p and miR-222-3p in microparticles, not in cells. Expression levels of miR-222-3p were lower in circulating microparticles from FH patients compared to normocholesterolemic controls. Microparticles derived from atherosclerotic plaque areas showed a decreased level of miR-143-3p and miR-222-3p compared to non atherosclerotic areas. CONCLUSIONS: We demonstrated for the first time that microparticles secreted by HCASMC contain microRNAs. Hypercholesterolemia alters the microRNA profile of HCASMC-derived microparticles. The miRNA signature of HCASMC-derived microparticles is a source of cardiovascular biomarkers. PMID- 27363782 TI - Construction of local gene network for revealing different liver function of rats fed deep-fried oil with or without resistant starch. AB - To study the mechanism underlying the liver damage induced by deep-fried oil (DO) consumption and the beneficial effects from resistant starch (RS) supplement, differential gene expression and pathway network were analyzed based on RNA sequencing data from rats. The up/down regulated genes and corresponding signaling pathways were used to construct a novel local gene network (LGN). The topology of the network showed characteristics of small-world network, with some pathways demonstrating a high degree. Some changes in genes led to a larger probability occurrence of disease or infection with DO intake. More importantly, the main pathways were found to be almost the same between the two LGNs (30 pathways overlapped in total 48) with gene expression profile. This finding may indicate that RS supplement in DO-containing diet may mainly regulate the genes that related to DO damage, and RS in the diet may provide direct signals to the liver cells and modulate its effect through a network involving complex gene regulatory events. It is the first attempt to reveal the mechanism of the attenuation of liver dysfunction from RS supplement in the DO-containing diet using differential gene expression and pathway network. PMID- 27363783 TI - Cucurbitacin E ameliorates hepatic fibrosis in vivo and in vitro through activation of AMPK and blocking mTOR-dependent signaling pathway. AB - The study evaluated the potential protective effect and underlying mechanism of Cucurbitacin E (CuE) in both thioacetamide-induced hepatic fibrosis and activated HSCs. CuE inhibited the proliferation of activated HSC/T-6 cells in a concentration- and time-dependent manner; triggered the activation of caspase-3, cleaved PARP, altered ratio of bcl-2-to-bax, and affected cytochrome C protein in a time- and concentration-dependent manner. CuE arrested activated HSCs at the G2/M phase. Furthermore, CuE reduced levels of p-Erk/MAPK and also inhibited the protein and mRNA expressions of alpha-SMA, TIMP-1 and collagen I in activated HSC T6 cells. CuE inhibited PI3K and Akt phosphorylation, and reduced the levels of p mTOR and p-P70S6K and increased the expression of p-AMPK, which is similar with AICAR and metformin. C57BL/6 mice were intraperitoneally injected with thioacetamide (TAA) for five continuous weeks (100 or 200mg/kg, three times per week) along with daily administration of CuE (5 or 10mg/kg/d) and curcumin (Cur, 20mg/kg). CuE treatments significantly reduced serum ALT/AST levels, alpha-SMA, TIMP-1, and collagen I protein expressions. HE, Masson trichrome, Sirius red and immunohistochemical staining also suggested that CuE could ameliorate hepatic fibrosis. Our findings suggest that CuE induces apoptosis of activated HSC and ameliorates TAA-induced hepatic fibrosis through activation of AMPK and blocking mTOR-dependent signaling pathway. PMID- 27363784 TI - T-2 toxin inhibits murine ES cells cardiac differentiation and mitochondrial biogenesis by ROS and p-38 MAPK-mediated pathway. AB - OBJECTIVE: To investigate the effect of T-2 toxin on murine embryonic stem cells (ESCs) cardiac differentiation and mitochondrial biogenesis in vitro. METHODS: Cardiac differentiation of the mouse ESCs was initiated by embryoid bodies (EBs) formation in hanging drops. EBs were exposed to 0.5ng/ml T-2 toxin for 24, 72 and 120h. Cultures were observed daily for the appearance of contracting clusters, and cardiac-specific protein (alpha-actiniin) were measured by Western blot and immunocytochemistry. Mitochondrial ultrastructure was observed by confocal laser scanning microscopy and transmission EM photography. Reactive oxygen species (ROS) was monitored by H2-dichlorofluorescein-diacetate (H2DCF-DA). The phosphorylation of the p38 (p-p38) and p38 mitogen-activated protein kinase (MAPK) and the expression of mitochondrial biogenesis proteins, including peroxisome proliferator activated receptor coactivator-1 alpha (PGC-1alpha), nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (mtTFA), and mitochondrial respiratory chain complex IV (COXIV) were analyzed using Western blot. In some experiments, mESCs were pre-treated with the antioxidant Trolox (200MUM) for 30min, then exposed to Trolox (200MUM) and T-2 toxin (0.5ng/ml) for 72h. RESULTS: Contracting clusters were observed under the microscope light and cardiac-specific protein (alpha-actinin) expressed positively indicated mESCs directly differentiated in cardiomyocytes. However, the cardiac differentiation was inhibited by T-2 toxin treatment 72 and 120h. ROS accumulated in murine ES cells in a time-dependent manner. The expression of p p38 significantly increased in 24h group and decrease in 72 and 120h groups. The decrease of mitochondrial number and the mitochondrial biogenesis-related proteins expression, including PGC-1alpha, NRF-1, mtTFA, and COXIV decreased in a time-dependent manner with T-2 toxin treatment. However, the inhibition of mitochondrial biogenesis by T-2 toxin in differentiated mESCs was recovered significantly in the presence of the antioxidant Trolox. CONCLUSION: Taken together, T-2 toxin decreased the expression of PGC-1alpha, NRF-1, and mtTFA, inhibited mitochondrial biogenesis, and then inhibited the cardiac differentiation of murine ES cells, and the effect was partly responsible for the p38 MAPK mediated by ROS. PMID- 27363785 TI - Cytotoxicity evaluation using cryopreserved primary human hepatocytes in various culture formats. AB - Sixteen training compounds selected in the IMI MIP-DILI consortium, 12 drug induced liver injury (DILI) positive compounds and 4 non-DILI compounds, were assessed in cryopreserved primary human hepatocytes. When a ten-fold safety margin threshold was applied, the non-DILI-compounds were correctly identified 2h following a single exposure to pooled human hepatocytes (n=13 donors) in suspension and 14-days following repeat dose exposure (3 treatments) to an established 3D-microtissue co-culture (3D-MT co-culture, n=1 donor) consisting of human hepatocytes co-cultured with non-parenchymal cells (NPC). In contrast, only 5/12 DILI-compounds were correctly identified 2h following a single exposure to pooled human hepatocytes in suspension. Exposure of the 2D-sandwich culture human hepatocyte monocultures (2D-sw) for 3days resulted in the correct identification of 11/12 DILI-positive compounds, whereas exposure of the human 3D-MT co-cultures for 14days resulted in identification of 9/12 DILI-compounds; in addition to ximelagatran (also not identified by 2D-sw monocultures, Sison-Young et al., 2016), the 3D-MT co-cultures failed to detect amiodarone and bosentan. The sensitivity of the 2D human hepatocytes co-cultured with NPC to ximelagatran was increased in the presence of lipopolysaccharide (LPS), but only at high concentrations, therefore preventing its classification as a DILI positive compound. In conclusion (1) despite suspension human hepatocytes having the greatest metabolic capacity in the short term, they are the least predictive of clinical DILI across the MIP-DILI test compounds, (2) longer exposure periods than 72h of human hepatocytes do not allow to increase DILI-prediction rate, (3) co-cultures of human hepatocytes with NPC, in the presence of LPS during the 72h exposure period allow the assessment of innate immune system involvement of a given drug. PMID- 27363786 TI - The Maternal Legacy: Female Identity Predicts Offspring Sex Ratio in the Loggerhead Sea Turtle. AB - In organisms with temperature-dependent sex determination, the incubation environment plays a key role in determining offspring sex ratios. Given that global temperatures have warmed approximately 0.6 degrees C in the last century, it is necessary to consider how organisms will adjust to climate change. To better understand the degree to which mothers influence the sex ratios of their offspring, we use 24 years of nesting data for individual female loggerhead sea turtles (Caretta caretta) observed on Bald Head Island, North Carolina. We find that maternal identity is the best predictor of nest sex ratio in univariate and multivariate predictive models. We find significant variability in estimated nest sex ratios among mothers, but a high degree of consistency within mothers, despite substantial spatial and temporal thermal variation. Our results suggest that individual differences in nesting preferences are the main driver behind divergences in nest sex ratios. As such, a female's ability to plastically adjust her nest sex ratios in response to environmental conditions is constrained, potentially limiting how individuals behaviorally mitigate the effects of environmental change. Given that many loggerhead populations already show female biased offspring sex ratios, understanding maternal behavioral responses is critical for predicting the future of long-lived species vulnerable to extinction. PMID- 27363787 TI - Effects of neonatal stress on gamma oscillations in hippocampus. AB - Chronic early life stress increases adult risk for depression, bipolar disorder and schizophrenia, illnesses characterized by aberrant functions of cognition and memory. We asked whether chronic early life stress disrupts maturation of gamma oscillations, on which these functions depend. Lifelong impairment of the stress response results from separation of rat pups from the dam for three hours per day during a critical period of hippocampal development (PNDs 2-14). Parvalbumin expressing interneurons, including the basket cell network which is fundamental to gamma oscillations, are reduced in number in post mortem studies of bipolar disorder and schizophrenia, and in chronically-stressed adult rats. To determine effects of chronic early life stress on gamma oscillations, we separated pups from dams once each day on PNDs 2-14 and recorded in vitro at PNDs 15-21. In control pups, separated for 15 minutes per day, gamma power had highly significant correlations with both age (p = 0.0022) and weight (p = 0.0024); gamma in pups separated for 180 minutes per day was not correlated with either factor. ANCOVA indicated significant differences between the groups in both measures. These findings indicate that chronic early life stress can disrupt maturation of the gamma oscillation network. PMID- 27363788 TI - Azaindole synthesis through dual activation catalysis with N-heterocyclic carbenes. AB - A convergent, transition-metal-free synthesis of 2-aryl-azaindoles has been developed. The interception of a reactive aza-ortho-azaquinone methide intermediate by an acyl anion equivalent generated through carbene catalysis provides high yields, a wide substrate scope, and the synthesis of previously inaccessible azaindoles. PMID- 27363808 TI - Indexing Effects of Copy Number Variation on Genes Involved in Developmental Delay. AB - A challenge in clinical genomics is to predict whether copy number variation (CNV) affecting a gene or multiple genes will manifest as disease. Increasing recognition of gene dosage effects in neurodevelopmental disorders prompted us to develop a computational approach based on critical-exon (highly expressed in brain, highly conserved) examination for potential etiologic effects. Using a large CNV dataset, our updated analyses revealed significant (P < 1.64 * 10(-15)) enrichment of critical-exons within rare CNVs in cases compared to controls. Separately, we used a weighted gene co-expression network analysis (WGCNA) to construct an unbiased protein module from prenatal and adult tissues and found it significantly enriched for critical exons in prenatal (P < 1.15 * 10(-50), OR = 2.11) and adult (P < 6.03 * 10(-18), OR = 1.55) tissues. WGCNA yielded 1,206 proteins for which we prioritized the corresponding genes as likely to have a role in neurodevelopmental disorders. We compared the gene lists obtained from critical-exon and WGCNA analysis and found 438 candidate genes associated with CNVs annotated as pathogenic, or as variants of uncertain significance (VOUS), from among 10,619 developmental delay cases. We identified genes containing CNVs previously considered to be VOUS to be new candidate genes for neurodevelopmental disorders (GIT1, MVB12B and PPP1R9A) demonstrating the utility of this strategy to index the clinical effects of CNVs. PMID- 27363809 TI - Alzheimer's disease Advax(CpG)- adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Abeta pathological molecules. AB - Although beta-amyloid (Abeta) may be the primary driver of Alzheimer's disease (AD) pathology, accumulation of pathological tau correlates with dementia in AD patients. Thus, the prevention/inhibition of AD may require vaccine/s targeting Abeta and tau simultaneously or sequentially. Since high antibody titers are required for AD vaccine efficacy, we have decided to generate vaccines, targeting Abeta (AV-1959R), Tau (AV-1980R) or Abeta/tau (AV-1953R) B cell epitopes, based on immunogenic MultiTEP platform and evaluate the immunogenicity of these vaccines formulated with Advax(CpG), delta inulin, Alhydrogel((r)), Montanide ISA51, Montanide-ISA720, MPLA-SM pharmaceutical grade adjuvants. Formulation of AV-1959R in Advax(CpG) induced the highest cellular and humoral immune responses in mice. The dual-epitope vaccine, AV-1953R, or the combination of AV-1959R and AV-1980R vaccines formulated with Advax(CpG) induced robust antibody responses against various forms of both, Abeta and tau pathological molecules. While anti Abeta antibody titers after AV-1953R immunization were similar to that in mice vaccinated with AV-1959R or AV-1959R/AV-1980R combination, anti-tau titers were significantly lower after AV-1953R injection when compared to the AV-1980R or AV 1959R/AV-1980R. In silico 3D-modeling provided insight into the differences in immunogenicity of these vaccine constructs. In sum, AV-1959R and AV-1980R formulated with Advax(CpG) adjuvant were identified as promising immunogenic vaccines for ongoing pre-clinical assessment and future human clinical trials. PMID- 27363810 TI - A centenary of Robert T. Leiper's lasting legacy on schistosomiasis and a COUNTDOWN on control of neglected tropical diseases. AB - Part of Robert T. Leiper's (1881-1969) lasting legacy in medical helminthology is grounded on his pioneering work on schistosomiasis (Bilharzia). Having undertaken many expeditions to the tropics, his fascination with parasite life cycles typically allowed him to devise simple preventive measures that curtailed transmission. Building on his formative work with others in Africa and Asia, and again in Egypt in 1915, he elucidated the life cycles of African schistosomes. His mandate, then commissioned by the British War Office, was to prevent and break transmission of this disease in British troops. This he did by raising standing orders based on simple water hygiene measures. Whilst feasible in military camp settings, today their routine implementation is sadly out of reach for millions of Africans living in poverty. Whilst we celebrate the centenary of Leiper's research we draw attention to some of his lesser known colleagues, then focus on schistosomiasis in Uganda discussing why expanded access to treatment with praziquantel is needed now. Looking to WHO 2020 targets for neglected tropical diseases, we introduce COUNTDOWN, an implementation research consortium funded by DFID, UK, which fosters the scale-up of interventions and confirm the current relevance of Leiper's original research. PMID- 27363813 TI - Sensitivity, Prediction Uncertainty, and Detection Limit for Artificial Neural Network Calibrations. AB - With the proliferation of multivariate calibration methods based on artificial neural networks, expressions for the estimation of figures of merit such as sensitivity, prediction uncertainty, and detection limit are urgently needed. This would bring nonlinear multivariate calibration methodologies to the same status as the linear counterparts in terms of comparability. Currently only the average prediction error or the ratio of performance to deviation for a test sample set is employed to characterize and promote neural network calibrations. It is clear that additional information is required. We report for the first time expressions that easily allow one to compute three relevant figures: (1) the sensitivity, which turns out to be sample-dependent, as expected, (2) the prediction uncertainty, and (3) the detection limit. The approach resembles that employed for linear multivariate calibration, i.e., partial least-squares regression, specifically adapted to neural network calibration scenarios. As usual, both simulated and real (near-infrared) spectral data sets serve to illustrate the proposal. PMID- 27363811 TI - Polysaccharide Nanoparticles for Efficient siRNA Targeting in Cancer Cells by Supramolecular pKa Shift. AB - Biomacromolecular pKa shifting is considered as one of the most ubiquitous processes in biochemical events, e.g., the enzyme-catalyzed reaction and protein conformational stabilization. In this paper, we report on the construction of biocompatible polysaccharide nanoparticle with targeting ability and lower toxicity by supramolecular pKa shift strategy. This was realized through a ternary assembly constructed by the dual host-guest interactions of an adamantane bis(diamine) conjugate (ADA) with cucurbit[6]uril (CB[6]) and a polysaccharide. The potential application of such biocompatible nanostructure was further implemented by the selective transportation of small interfering RNA (siRNA) in a controlled manner. It is demonstrated that the strong encapsulation of the ADA's diammonium tail by CB[6] not only reduced the cytotoxicity of the nano-scaled vehicle but also dramatically enhanced cation density through an obvious positive macrocycle-induced pKa shift, which eventually facilitated the subsequent siRNA binding. With a targeted polysaccharide shell containing a cyclodextrin hyaluronic acid conjugate, macrocycle-incorporated siRNA polyplexes were specifically delivered into malignant human prostate PC-3 cells. The supramolecular polysaccharide nanoparticles, the formation of which was enabled and promoted by the complexation-assisted pKa shift, may be used as a versatile tool for controlled capture and release of biofunctional substrates. PMID- 27363814 TI - Report of the results of the International Clinical Cytometry Society and American Society for Clinical Pathology workload survey of clinical flow cytometry laboratories. AB - BACKGROUND: Thorough review of current workload, staffing, and testing practices in clinical laboratories allows for optimization of laboratory efficiency and quality. This information is largely missing with regard to clinical flow cytometry laboratories. The purpose of this survey is to provide comprehensive, current, and accurate data on testing practices and laboratory staffing in clinical laboratories performing flow cytometric studies. METHODS: Survey data was collected from flow cytometry laboratories through the ASCP website. Data was collected on the workload during a 1-year time period of full-time and part-time technical and professional (M.D./D.O./Ph.D. or equivalent) flow cytometry employees. Workload was examined as number of specimens and tubes per full time equivalent (FTE) technical and professional staff. Test complexity, test result interpretation, and reporting practices were also evaluated. RESULTS: There were 205 respondent laboratories affiliated predominantly with academic and health system institutions. Overall, 1,132 FTE employees were reported with 29% professional FTE employees and 71% technical. Fifty-one percent of the testing performed was considered high complexity and 49% was low complexity. The average number of tubes per FTE technologist was 1,194 per year and the average number of specimens per FTE professional was 1,659 per year. The flow cytometry reports were predominantly written by pathologists (57%) and were typically written as a separate report (58%). CONCLUSIONS: This survey evaluates the overall status of the current practice of clinical flow cytometry and provides a comprehensive dataset as a framework to help laboratory departments, directors, and managers make appropriate, cost-effective staffing decisions. (c) 2016 International Clinical Cytometry Society. PMID- 27363812 TI - Neutrophils mediate Salmonella Typhimurium clearance through the GBP4 inflammasome-dependent production of prostaglandins. AB - Inflammasomes are cytosolic molecular platforms that alert the immune system about the presence of infection. Here we report that zebrafish guanylate-binding protein 4 (Gbp4), an IFNgamma-inducible GTPase protein harbouring a C-terminal CARD domain, is required for the inflammasome-dependent clearance of Salmonella Typhimurium (ST) by neutrophils in vivo. Despite the presence of the CARD domain, Gbp4 requires the universal inflammasome adaptor Asc for mediating its antibacterial function. In addition, the GTPase activity of Gbp4 is indispensable for inflammasome activation and ST clearance. Mechanistically, neutrophils are recruited to the infection site through the inflammasome-independent production of the chemokine (CXC motif) ligand 8 and leukotriene B4, and then mediate bacterial clearance through the Gbp4 inflammasome-dependent biosynthesis of prostaglandin D2. Our results point to GBPs as key inflammasome adaptors required for prostaglandin biosynthesis and bacterial clearance by neutrophils and suggest that transient activation of the inflammasome may be used to treat bacterial infections. PMID- 27363815 TI - Erratum. PMID- 27363816 TI - Submaximal fitness and mortality risk reduction in coronary heart disease: a retrospective cohort study of community-based exercise rehabilitation. AB - OBJECTIVES: To examine the association between submaximal cardiorespiratory fitness (sCRF) and all-cause mortality in a cardiac rehabilitation (CR) cohort. DESIGN: Retrospective cohort study of participants entering CR between 26 May 1993 and 16 October 2006, followed up to 1 November 2013 (median 14 years, range 1.2-19.4 years). SETTING: A community-based CR exercise programme in Leeds, West Yorkshire, UK. PARTICIPANTS: A cohort of 534 men (76%) and 136 women with a clinical diagnosis of coronary heart disease (CHD), aged 22-82 years, attending CR were evaluated for the association between baseline sCRF and all-cause mortality. 416 participants with an exercise test following CR (median 14 weeks) were examined for changes in sCRF and all-cause mortality. MAIN OUTCOME MEASURES: All-cause mortality and change in sCRF expressed in estimated metabolic equivalents (METs). RESULTS: Baseline sCRF was a strong predictor of all-cause mortality; compared to the lowest sCRF group (<5 METs for women and <6 METs for men), mortality risk was 41% lower in those with moderate sCRF (HR 0.59; 95% CI 0.42 to 0.83) and 60% lower (HR 0.40; 95% CI 0.25 to 0.64) in those with higher sCRF levels (>=7 METs women and >=8 METs for men). Although improvement in sCRF at 14 weeks was not associated with a significant mortality risk reduction (HR 0.91; 95% CI 0.79 to 1.06) for the whole cohort, in those with the lowest sCRF (and highest all-cause mortality) at baseline, each 1-MET improvement was associated with a 27% age-adjusted reduction in mortality risk (HR 0.73; 95% CI 0.57 to 0.94). CONCLUSIONS: Higher baseline sCRF is associated with a reduced risk of all-cause mortality over 14 years in adults with CHD. Improving fitness through exercise-based CR is associated with significant risk reduction for the least fit. PMID- 27363817 TI - Validation of the Compassion Fatigue Short Scale among Chinese medical workers and firefighters: a cross-sectional study. AB - OBJECTIVES: To examine the psychometric properties of the Chinese version of the C-Compassion Fatigue (CF)-Short Scale among 4 independent samples of Chinese emergency workers (medical workers and firefighters). DESIGN: Cross-sectional. SETTING: 6 hospitals in Zhejiang Province and 12 fire stations in Shanghai. PARTICIPANTS: Emergency workers (medical and firefighters) were consecutively recruited and divided into 4 groups: the MW1 group (medical workers, n=167), the FF1 group (firefighters, n=157), the MW2 group (medical workers, n=265) and the FF2 group (firefighters, n=231). INTERVENTIONS: All patients completed the C-CF Short Scale to identify factors associated with compassion fatigue. The MW1 and FF1 groups were used for the exploratory analyses. The MW2 and FF2 groups were used for the confirmatory factor analyses. PRIMARY AND SECONDARY OUTCOME MEASURES: Factor loading, correlations with previously validated questionnaires (the Ego-Resiliency Scale, the Social Support Questionnaire and the Job Pressure Scale) and Cronbach's alpha coefficient were tested for each factor. RESULTS: The C-CF-Short Scale demonstrated excellent construct validity and good internal consistency. Specifically, the results of exploratory factor analyses in the MW1 and FF1 groups showed that secondary trauma and job burnout were associated with compassion fatigue in these emergency workers. The confirmatory factor analyses in the MW2 and FF2 groups indicated that all the fit indices of the 2-factor model were satisfactory. Finally, the Cronbach's alpha coefficient of each factor was excellent. CONCLUSIONS: The findings suggest that the C-CF-Short Scale has good psychometric properties and can be applied to study Chinese emergency workers. PMID- 27363818 TI - Regulatory approval of pharmaceuticals without a randomised controlled study: analysis of EMA and FDA approvals 1999-2014. AB - INTRODUCTION: The efficacy of pharmaceuticals is most often demonstrated by randomised controlled trials (RCTs); however, in some cases, regulatory applications lack RCT evidence. OBJECTIVE: To investigate the number and type of these approvals over the past 15 years by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). METHODS: Drug approval data were downloaded from the EMA website and the 'Drugs@FDA' database for all decisions on pharmaceuticals published from 1 January 1999 to 8 May 2014. The details of eligible applications were extracted, including the therapeutic area, type of approval and review period. RESULTS: Over the period of the study, 76 unique indications were granted without RCT results (44 by the EMA and 60 by the FDA), demonstrating that a substantial number of treatments reach the market without undergoing an RCT. The majority was for haematological malignancies (34), with the next most common areas being oncology (15) and metabolic conditions (15). Of the applications made to both agencies with a comparable data package, the FDA granted more approvals (43/44 vs 35/44) and took less time to review products (8.7 vs 15.5 months). Products reached the market first in the USA in 30 of 34 cases (mean 13.1 months) due to companies making FDA submission before EMA submissions and faster FDA review time. DISCUSSION: Despite the frequency with which approvals are granted without RCT results, there is no systematic monitoring of such treatments to confirm their effectiveness or consistency regarding when this form of evidence is appropriate. We recommend a more open debate on the role of marketing authorisations granted without RCT results, and the development of guidelines on what constitutes an acceptable data package for regulators. PMID- 27363819 TI - Efficacy and safety of bevacizumab plus erlotinib versus bevacizumab or erlotinib alone in the treatment of non-small-cell lung cancer: a systematic review and meta-analysis. AB - OBJECTIVES: Bevacizumab and erlotinib inhibit different tumour growth pathways, and both exhibit beneficial effects in the treatment of non-small-cell lung cancer (NSCLC). However, the efficacy of bevacizumab in combination with erlotinib remains controversial. Therefore, we conducted a meta-analysis to compare combination treatment with bevacizumab and erlotinib to bevacizumab or erlotinib monotherapy in the treatment of NSCLC. METHODS: Randomised controlled trials (RCTs) published in PubMed, Web of Science and EMBASE were systematically reviewed. The main outcome measures included overall survival (OS), progression free survival (PFS), overall response rate (ORR) and adverse events. Results were expressed as HRs or risk ratios (RRs) with 95% CIs. RESULTS: 5 RCTs involving a total of 1736 patients were included in this meta-analysis. The combination of bevacizumab and erlotinib significantly improved PFS (HR=0.63, 95% CI 0.53 to 0.75; p=0.000) and the ORR (RR=1.91, 95% CI 1.19 to 3.06; p=0.007) in the second line treatment of NSCLC compared with bevacizumab or erlotinib alone. However, no significant difference in OS was observed between the combination and monotherapy groups (HR=0.96, 95% CI 0.83 to 1.11; p=0.573). A subgroup analysis has shown that the greatest PFS benefit was associated with an age of <65 years(HR=0.74, 95% CI 0.57 to 0.96; p=0.026), Asian/Pacific Islander ethnicity (HR=0.23, 95% CI 0.10 to 0.54; p=0.001), Eastern Cooperative Oncology Group performance status (ECOG PS) 1 (HR=0.82, 95% CI 0.68 to 0.98; p=0.033), stage IIIB or IV disease (HR=0.68, 95% CI 0.57 to 0.82; p=0.000) and no history of smoking (HR=0.48, 95% CI 0.32 to 0.71; p=0.000). The incidence of grade 3/4 adverse events such as rash and diarrhoea was higher in the combination group than in the monotherapy group. CONCLUSIONS: The addition of bevacizumab to erlotinib can significantly improve PFS and the ORR in the second-line treatment of NSCLC with an acceptable and manageable risk of rash and diarrhoea. Further well-conducted, large-scale trials are needed to validate these findings. PMID- 27363821 TI - Cytomegalovirus Ocular Involvement in a Kidney Transplant Recipient. AB - Cytomegalovirus remains the most common infection after kidney transplant. We report cytomegalovirus retinitis and anterior uveitis, which developed consecutively within 1 year in a kidney transplant recipient. A 25-year-old man presented 5 months after transplant with decreased visual acuity in his left eye. Fundus examination revealed bilateral areas of necrotizing retinitis with intraretinal hemorrhages. The confirmation of cytomegalovirus disease was based on clinical findings and positive polymerase chain reaction for cytomegalovirus in plasma and in aqueous humor. The patient was treated with intravenous ganciclovir for 21 days and then with valacyclovir for 3 months. The patient's symptoms improved, and fundus examination revealed resolution of retinitis with appearance of retinal scarring. One year later, the patient presented with cytomegalovirus anterior uveitis associated with increased intraocular pressure, which was treated with antiviral agents, antiglaucomatous eye drops, and trabeculectomy. Cytomegalovirus ocular involvement for our immunocompromised patient presented in 2 consecutive forms: bilateral retinitis and anterior uveitis. Early diagnosis and treatment of active cytomegalovirus retinitis and uveitis remain crucial to prevent their progression to irreversible visual impairment. PMID- 27363820 TI - Investigating the relationship between substance use and sexual behaviour in young people in Britain: findings from a national probability survey. AB - BACKGROUND: Health risk behaviours are prominent in late adolescence and young adulthood, yet UK population-level research examining the relationship between drug or alcohol use and sexual health and behaviour among young people is scarce, despite public health calls for an integrated approach to health improvement. Our objective was to further our understanding of the scale of and nature of any such relationship, using contemporary data from Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). METHODS: Analyses of data from Natsal 3, a stratified probability survey of 15 162 men and women (3869 aged 16-24 years), undertaken in 2010-2012, using computer-assisted personal interviewing, were carried out. Logistic regression was used to explore associations between reporting (1) frequent binge drinking (>=weekly), (2) recent drug use (within past 4 weeks) or (3) multiple (both types of) substance use, and key sexual risk behaviours and adverse sexual health outcomes. We then examined the sociodemographic profile, health behaviours and attitudes reported by 'risky' young people, defined as those reporting >=1 type of substance use plus non condom use at first sex with >=1 new partner(s), last year. RESULTS: Men and women reporting frequent binge drinking or recent drug use were more likely to report: unprotected first sex with >=1 new partner(s), last year; first sex with their last partner after only recently meeting; emergency contraception use (last year) and sexually transmitted infection diagnosis/es (past 5 years). Associations with sexual risk were frequently stronger for those reporting multiple substance use, particularly among men. The profile of 'risky' young people differed from that of other 16-24 years old. CONCLUSIONS: In this nationally representative study, substance use was strongly associated with sexual risk and adverse sexual health outcomes among young people. Qualitative or event-level research is needed to examine the context and motivations behind these associations to inform joined-up interventions to address these inter related behaviours. PMID- 27363822 TI - A substudy evaluating treatment intensification on medication adherence among hypertensive patients receiving home blood pressure telemonitoring and pharmacist management. AB - WHAT IS KNOWN AND OBJECTIVE: Hypertension is a leading cause of death and major contributor to heart attacks, strokes, heart and kidney failure. Antihypertensive (HTN medication) non-adherence contributes to uncontrolled hypertension. Effective initiatives to improve uncontrolled hypertension include a team-based approach with home blood pressure (BP) monitoring. Our study objective was to evaluate whether objectively measured medication adherence was influenced by home BP telemonitoring and pharmacist management. METHODS: We analysed HTN medication adherence in 240 patients who received home BP telemonitoring and pharmacist intervention (TI). Adherence was measured based on prescription fills and the proportion of days covered (PDC). HTN medications continued pre- to post-baseline were similar for telemonitoring intervention (TI) and usual care (UC) patients (rate ratio = 1.00, P = 0.90). RESULTS AND DISCUSSION: More HTN medications were discontinued pre- to post-baseline in TI patients (rate ratio = 1.38, P = 0.04). Similarly, more HTN medications were added in TI patients (rate ratio = 2.46, P < 0.001). The proportion with a mean PDC >= 0.8 for HTN medications added after baseline and overall adherence did not differ between groups. WHAT IS NEW AND CONCLUSION: Medication adherence was high in both groups; however, medication adherence was not significantly altered by the intervention. There were more medication modifications and greater medication intensification among TI patients. PMID- 27363823 TI - The Impact of Cocoa Flavanols on Cardiovascular Health. AB - The aim of the study was to review the effect of cocoa flavanols on cardiovascular health, with emphasis on the doses ingested, and to analyze a range of cocoa products for content of these compounds. PubMed was searched from 2010 to locate systematic reviews (SR) on clinical effects of chocolate consumption. Thirteen SRs were identified and reviewed, and provided strong evidence that dark chocolate did not reduce blood pressure. The evidence was however strong for an association with increased flow-mediated vasodilatation (FMD) and moderate for an improvement in blood glucose and lipid metabolism. Our analysis showed that cocoa products with around 100 mg epicatechin can reliably increase FMD, and that cocoa flavanol doses of around 900 mg or above may decrease blood pressure in specific individuals and/or if consumed over longer periods. Out of 32 cocoa product samples analyzed, the two food supplements delivered 900 mg of total flavanols and 100 mg epicatechin in doses of 7 g and 20 g and 3 and 8 g, respectively. To achieve these doses with chocolate, around 100 to 500 g (for 900 mg flavanols) and 50 to 200 g (for 100 mg epicatechin) would need to be consumed. Chocolate products marketed for their purported health benefits should therefore declare the amounts of total flavanols and epicatechin. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27363824 TI - American Heart Association's Ideal Cardiovascular Health Metrics in Under Represented Asian Americans. AB - The American Heart Association's ideal cardiovascular health score is based on 7 cardiovascular health metrics to measure progress toward their Impact Goal of reducing cardiovascular disease by 20 % before 2020. This study applied this construct to assess cardiovascular health in a sample of Asian Americans. Convenience sampling methods were used to enroll self-identified Asian American's over the age of 18 years who were attending community health fairs across the greater Philadelphia and urban areas of New Jersey. The heart health metrics of tobacco use, body mass index, physical activity, diet, blood pressure, and glucose were measured. In the greater sample (N = 541), 82 % were female, the mean age was 65.1 (SD = 15.5) years, 45 % were Vietnamese, 38 % were Chinese and 17 % were Korean. Prevalence of ideal heart health for the metrics of tobacco use (95 %) was high. Only 19.4 % achieved ideal levels of physical activity, 35.1 % for BMI, 28.9 % for glucose and 66 % for blood pressure. Dietary intake was ideal for 20.7 % of the sample. More years since migration and Korean race trended toward having a higher prevalence of poor health in some metrics. Most Asian Americans are not achieving ideal cardiovascular health for several of the metrics evaluated, with those residing in the United States for more than 13 years and Korean Americans being higher-risk groups. Targeted community based intervention approaches to improving and monitoring heart health in Asian American, and Asian American subgroups, are needed. PMID- 27363825 TI - Risk of Developing Diabetes Among Refugees and Immigrants: A Longitudinal Analysis. AB - To determine the difference in risk of developing diabetes for refugees, immigrants, and American-born participants living in the same communities, and to explore potential mediators of that difference. Retrospective longitudinal cohort from January 1, 2003 and December 31, 2013. Refugees aged >=18 years were matched in a 1:3 ratio by age, gender, and date of care initiation to (1) Spanish speaking non-refugee immigrants, and (2) English-speaking controls receiving care in the same community health center. We used proportional hazards regression to estimate the risk of incident diabetes. We tested whether differences in education or baseline obesity mediated diabetes risk using counterfactual mediation analysis. We included 3174 participants. Among refugee participants, the most common countries of origin were Somalia (17.8 %), Iraq (16.7 %) and Bhutan (8.8 %). Diabetes incidence rate was 1.94, 1.91, and 1.22 cases per 100 person-years follow-up for refugees, immigrants, and controls, respectively. In adjusted models, both refugee (HR 2.08 95 % CI 1.32-3.30) and immigrant (HR 1.51 95 % CI 1.01-2.24) statuses were associated with increased diabetes risk compared with controls. Risk between refugees and immigrants did not differ (adjusted HR for refugees 1.37 95 % CI 0.91-2.06). In mediation analyses, educational attainment mediated 36 % (p = 0.007) of the difference in diabetes risk between refugees/immigrants and controls. Baseline obesity did not mediate difference in diabetes risk (proportion mediated 1 %, p = 0.84). Refugees and immigrants had significantly increased risk for diabetes, partially mediated by education. Education-based lifestyle interventions may be a promising strategy to prevent diabetes for these vulnerable patients. PMID- 27363826 TI - Endocrine-disrupting chemicals and skin manifestations. AB - Endocrine-disrupting chemicals (EDCs) are exogenous compounds that have the ability to disrupt the production and actions of hormones through direct or indirect interaction with hormone receptors, thus acting as agonists or antagonists. Human health is affected after either individual occupation or dietary and environmental exposure to EDCs. On the other hand, skin is one of the largest organs of the body and its main function is protection from noxious substances. EDCs perturb the endocrine system, and they are also carcinogenic, immunotoxic, and hepatotoxic to human skin. In addition, their effects on keratinocytes, melanocytes, sebocytes, inflammatory and immunological cells, and skin stem cells produce inflammatory and allergic skin diseases, chloracne, disorders of skin pigmentation, skin cancer, and skin aging. Mechanisms, which EDCs use to induce these skin disorders are complicated, and involve the interference of endogenous hormones and most importantly the activation of the aryl hydrocarbon receptor signal pathway. Further studies on EDCs and skin diseases are necessary to elucidate these mechanisms. PMID- 27363827 TI - New approach to age estimation of male and female adult skeletons based on the morphological characteristics of the acetabulum. AB - Age estimation is essential to the human identification process, both in forensic and archeological contexts. Based on the previous male-specific method of Rissech et al. (J Forensic Sci, 2006, 51:213-229), a new approach to age estimation based on the acetabulum has been described and evaluated in 611 individuals from the Lisbon Collection (Lisbon, Portugal). This paper has two main goals: (1) to revise and better define the variables of Rissech's method related to the acetabular fossa, namely, variables 5, 6, and 7, and (2) to extend the applicability of this new approach to both sexes while analyzing age-related sex differences in the acetabular aging process. The results demonstrate the suitability of combining acetabulum traits and a Bayesian approach to estimating age in adults of both sexes. This study has confirmed the usefulness of the redefined variables of the acetabular fossa when age-related changes are considered. Furthermore, the newly defined variables have good to excellent values of repeatability. The study has also extended the method's applicability to females. The revised method has absolute error averages of 7.28 years for males and 7.09 years for females, based on a sex-specific reference sample. In addition, approximately 74 % of the individuals estimated had an absolute error less than 10 years. Interestingly, the acetabular aging process follows similar trends in both sexes, but the aging rate seems to be different between males and females, especially in middle-aged individuals. Despite the fact that the age estimates, on average, did not improve significantly with the use of a sex specific reference sample, it is recommended that the sexes be analyzed separately due to the differences in aging rates and inaccuracy values. PMID- 27363829 TI - Abdominal Sepsis. AB - Abdominal infections are an important challenge for the intensive care physician. In an era of increasing antimicrobial resistance, selecting the appropriate regimen is important and, with new drugs coming to the market, correct use is important more than ever before and abdominal infections are an excellent target for antimicrobial stewardship programs. Biomarkers may be helpful, but their exact role in managing abdominal infections remains incompletely understood. Source control also remains an ongoing conundrum, and evidence is increasing that its importance supersedes the impact of antibiotic therapy. New strategies such as open abdomen management may offer added benefit in severely ill patients, but more data are needed to identify its exact role. The role of fungi and the need for antifungal coverage, on the other hand, have been investigated extensively in recent years, but at this point, it remains unclear who requires empirical as well as directed therapy. PMID- 27363828 TI - Thiol oxidation of hemolymph proteins in oysters Crassostrea brasiliana as markers of oxidative damage induced by urban sewage exposure. AB - Urban sewage is a concerning issue worldwide, threatening both wildlife and human health. The present study investigated protein oxidation in mangrove oysters (Crassostrea brasiliana) exposed to seawater from Balneario Camboriu, an important tourist destination in Brazil that is affected by urban sewage. Oysters were exposed for 24 h to seawater collected close to the Camboriu River (CAM1) or 1 km away (CAM2). Seawater from an aquaculture laboratory was used as a reference. Local sewage input was marked by higher levels of coliforms, nitrogen, and phosphorus in seawater, as well as polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), linear alkylbenzenes (LABs), and fecal steroid in sediments at CAM1. Exposure of oysters to CAM1 caused marked bioaccumulation of LABs and decreased PAH and PCB concentrations after exposure to both CAM1 and CAM2. Protein thiol oxidation in gills, digestive gland, and hemolymph was evaluated. Lower levels of reduced protein thiols were detected in hemolymph from CAM1, and actin, segon, and dominin were identified as targets of protein thiol oxidation. Dominin susceptibility to oxidation was confirmed in vitro by exposure to peroxides and hypochlorous acid, and 2 cysteine residues were identified as potential sites of oxidation. Overall, these data indicate that urban sewage contamination in local waters has a toxic potential and that protein thiol oxidation in hemolymph could be a useful biomarker of oxidative stress in bivalves exposed to contaminants. Environ Toxicol Chem 2017;36:1833-1845. (c) 2016 SETAC. PMID- 27363830 TI - Is Vitamin C Beneficial to Patients with CAP? AB - Community-acquired pneumonia (CAP) is one of the most common causes of morbidity and mortality in elderly and children. Vitamin C is known as a physiological antioxidant, regulating innate immune system in the lung. Vitamin C has been used to prevent and treat CAP. However, the use of vitamin C for preventing and treating CAP has been a subject of controversy. We aim to review the most significant findings about vitamin C supplementation in patients with pneumonia based on literature from the PubMed. First, we reviewed recent advances about the role of oxidative stress in CAP. Oxidative stress is a crucial component of the host defense system and inflammatory response. However, excessive oxidative stress can cause a systemic inflammatory response leading to tissue damage. The degree of oxidative stress has been associated with the severity of CAP. Vitamin C is beneficial to the host defense system by regulating the innate immunity in the lungs. We also discuss the prophylactic use of vitamin C for pneumonia. Vitamin C supplementation decreased the pneumonia risk in patients with vitamin C deficiency. However, it is not beneficial for prophylactic use of vitamin C to prevent pneumonia in the well-nourished population. Finally, we summarize the effect of vitamin C on mechanical ventilation used during respiratory failure. Administration of vitamin C decreases the duration of mechanical ventilation by decreasing oxidative stress. PMID- 27363831 TI - Gastrointestinal Health in Classic Galactosemia. AB - Classic galactosemia (CG) is an autosomal recessive disorder of galactose metabolism that affects approximately 1/50,000 live births in the USA. Following exposure to milk, which contains large quantities of galactose, affected infants may become seriously ill. Early identification by newborn screening with immediate dietary galactose restriction minimizes or prevents the potentially lethal acute symptoms of CG. However, more than half of individuals with CG still experience long-term complications including cognitive disability, behavioral problems, and speech impairment. Anecdotal reports have also suggested frequent gastrointestinal (GI) problems, but this outcome has not been systematically addressed. In this study we explored the prevalence of GI symptoms among 183 children and adults with CG (cases) and 190 controls. Cases reported 4.5 times more frequent constipation (95% CI 1.8-11.5) and 4.2 times more frequent nausea (95% CI 1.2-15.5) than controls. Cases with genotypes predicting residual GALT activity reported less frequent constipation than cases without predicted GALT activity but this difference was not statistically significant. Because the rigor of dietary galactose restriction varies among individuals with galactosemia, we further tested whether GI symptoms associated with diet in infancy. Though constipation was almost four times as common among cases reporting a more restrictive diet in infancy, this difference was not statistically significant. These data confirm that certain GI symptoms are more common in classic galactosemia compared to controls and suggest that future studies should investigate associations with residual GALT activity and dietary galactose restriction in early life. PMID- 27363833 TI - Upregulation of Key Molecules for Targeted Imaging and Therapy. AB - : Targeted diagnosis and therapy enable precise tumor detection and treatment. Successful examples for precise tumor targeting are diagnostic and therapeutic radioligands. However, patients with tumors expressing low levels of the relevant molecular targets are deemed ineligible for such targeted approaches. METHODS: We performed a screen for drugs that upregulate the somatostatin receptor subtype 2 (sstr2). Then, we characterized the effects of these drugs on transcriptional, translational, and functional levels in vitro and in vivo. RESULTS: We identified 9 drugs that act as epigenetic modifiers, including the inhibitor of DNA methyltransferase decitabine as well as the inhibitors of histone deacetylase tacedinaline and romidepsin. In vitro, these drugs upregulated sstr2 on transcriptional, translational, and functional levels in a time- and dose dependent manner. Thereby, their combinations revealed synergistic effects. In vivo, drug-based sstr2 upregulation improved the tumor-to-background and tumor-to kidney ratios, which are the key determinants of successful sstr2-targeted imaging and radiopeptide therapy. CONCLUSION: We present an approach that uses epigenetic modifiers to improve sstr2 targeting in vitro and in vivo. Translation of this method into the clinic may potentially convert patients ineligible for targeted imaging and therapy to eligible candidates. PMID- 27363832 TI - Novel agents in the treatment of multiple myeloma: a review about the future. AB - Multiple myeloma (MM) is a disease that affects plasma cells and can lead to devastating clinical features such as anemia, lytic bone lesions, hypercalcemia, and renal disease. An enhanced understanding of MM disease mechanisms has led to new more targeted treatments. There is now a plethora of treatments available for MM. In this review article, our aim is to discuss many of the novel agents that are being studied or have recently been approved for the treatment of MM. These agents include the following: immunomodulators (pomalidomide), proteasome inhibitors (carfilzomib, marizomib, ixazomib, oprozomib), alkylating agents (bendamustine), AKT inhibitors (afuresertib), BTK inhibitors (ibrutinib), CDK inhibitors (dinaciclib), histone deacetylase inhibitors (panobinostat, rocilinostat, vorinostat), IL-6 inhibitors (siltuximab), kinesin spindle protein inhibitors (filanesib), monoclonal antibodies (daratumumab, elotuzumab, indatuximab, SAR650984), and phosphoinositide 3-kinase (PI3K) inhibitors. PMID- 27363835 TI - Reply: Somatostatin Receptor-Targeted Radiopeptide Therapy in Patients with Progressive Unresectable Meningioma. PMID- 27363834 TI - Absolute Myocardial Blood Flow and Flow Reserve Assessed by Gated SPECT with Cadmium-Zinc-Telluride Detectors Using 99mTc-Tetrofosmin: Head-to-Head Comparison with 13N-Ammonia PET. AB - : Recent advances in SPECT technology including cadmium-zinc-telluride (CZT) semiconductor detector material may pave the way for absolute myocardial blood flow (MBF) measurements by SPECT. The aim of the present study was to compare K1 uptake rate constants as surrogates of absolute MBF and myocardial flow reserve index (MFRi) in humans as assessed with a CZT SPECT camera versus PET. METHODS: Absolute MBF was assessed in 28 consecutive patients undergoing adenosine stress rest myocardial perfusion imaging (MPI) by 99mTc-tetrofosmin CZT SPECT and 13N ammonia PET, and MFR was calculated as a ratio of hyperemic over resting MBF. Results from both MPI methods were compared, and correlation coefficients were calculated. The diagnostic accuracy of CZT MFRi to predict an abnormal MFR defined as PET MFR less than 2 was assessed using a receiver-operator characteristic curve. RESULTS: Median MBF at rest was comparable between CZT and PET (0.89 [interquartile range (IQR), 0.77-1.00] vs. 0.92 [IQR, 0.78-1.06] mL/g/min; P = not significant) whereas it was significantly lower at stress in CZT than PET (1.11 [IQR, 1.00-1.26] vs. 2.06 [IQR, 1.48-2.56] mL/g/min; P < 0.001). This resulted in median MFRi values of 1.32 (IQR, 1.13-1.52) by CZT and 2.36 (IQR, 1.57-2.71) by PET (P < 0.001). The receiver-operator-characteristic curve revealed a cutoff for CZT MFRi at 1.26 to predict an abnormal PET MFR yielding an accuracy of 75%. CONCLUSION: The estimation of absolute MBF index values by CZT SPECT MPI with 99mTc-tetrofosmin is technically feasible, although hyperemic values are significantly lower than from PET with 13N-ammonia, resulting in a substantial underestimation of MFR. Nevertheless, CZT MFRi may confer diagnostic value. PMID- 27363837 TI - Reply: High Impact of Preferential Flow on 99mTc-MAA and 90Y-Loaded Microsphere Uptake Correlation. PMID- 27363836 TI - Cerebellar Amyloid-beta Plaques: How Frequent Are They, and Do They Influence 18F Florbetaben SUV Ratios? AB - : SUV ratios (SUVRs) are used for relative quantification of 18F-florbetaben scans. The cerebellar cortex can be used as a reference region for quantification. However, cerebellar amyloid-beta (Abeta) plaques may be present in Alzheimer disease (AD). The aim of this study was to assess the influence of Abeta pathology, including neuritic plaques, diffuse plaques, and vascular deposits, in 18F-florbetaben SUVR when cerebellum is used as the reference. METHODS: Using immunohistochemistry to demonstrate Abeta plaques and vascular deposits, and using the Bielschowsky method to demonstrate neuritic plaques, we performed a neuropathologic assessment of the frontal, occipital, anterior cingulate, and posterior cingulate cerebral cortices and the cerebellar cortex of 87 end-of-life patients (64 with AD, 14 with other types of dementia, and 9 nondemented aged volunteers; mean age +/- SD, 80.4 +/- 10.2 y) who had undergone 18F-florbetaben PET before death. The lesions were rated as absent (none or sparse) or present (moderate or frequent). Mean cortical SUVRs were compared among cases with different cerebellar Abeta loads. RESULTS: None of the 83 evaluable cerebellar samples showed frequent diffuse Abeta or neuritic plaques; 8 samples showed frequent vascular Abeta deposits. Diffuse Abeta plaques were rated as absent in 78 samples (94%) and present in 5 samples (6%). Vascular Abeta was rated as absent in 62 samples (74.7%) and present in 21 samples (25.3%). No significant differences in cerebellar SUVs were found among cases with different amounts or types of Abeta deposits in the cerebral cortex. Both diffuse and neuritic plaques were found in the cerebral cortex of 26-44 cases. No significant SUVR differences were found between these brains with different cerebellar Abeta loads. CONCLUSION: The effect of cerebellar plaques on cortical 18F-florbetaben SUVRs appears to be negligible even in advanced stages of AD with a higher cerebellar Abeta load. PMID- 27363838 TI - A Continuously Infused Microfluidic Radioassay System for the Characterization of Cellular Pharmacokinetics. AB - : Measurement of cellular tracer uptake is widely applied to learn the physiologic status of cells and their interactions with imaging agents and pharmaceuticals. In-culture measurements have the advantage of less stress to cells. However, the tracer solution still needs to be loaded, unloaded, and purged from the cell culture during the measurements. Here, we propose a continuously infused microfluidic radioassay (CIMR) system for continuous in culture measurement of cellular uptake. The system was tested to investigate the influence of the glucose concentration in cell culture media on 18F-FDG uptake kinetics. METHODS: The CIMR system consists of a microfluidic chip integrated with a flow-control unit and a positron camera. Medium diluted with radioactive tracer flows through a cell chamber continuously at low speed. Positrons emitted from the cells and from tracer in the medium are measured with the positron camera. The human cell lines SkBr3 and Capan-1 were incubated with media of 3 different glucose concentrations and then measured with 18F-FDG on the CIMR system. In addition, a conventional uptake experiment was performed. The relative uptake ratios between different medium conditions were compared. A cellular 2 compartment model was applied to estimate the cellular pharmacokinetics on CIMR data. The estimated pharmacokinetic parameters were compared with expressions of glucose transporter-1 (GLUT1) and hexokinase-2 measured by quantitative real-time polymerase chain reaction. RESULTS: The relative uptake ratios obtained from CIMR measurements correlated significantly with those from the conventional uptake experiments. The relative SDs of the relative uptake ratios obtained from the CIMR uptake experiments were significantly lower than those from the conventional uptake experiments. The fit of the cellular 2-compartment model to the 18F-FDG CIMR measurements was of high quality. For SkBr3, the estimated pharmacokinetic parameters k1 and k3 were consistent with the messenger RNA expression of GLUT1 and hexokinase-2: culturing with low glucose concentrations led to higher GLUT1 and hexokinase-2 expression as well as higher estimated k1 and k3 For Capan-1, the estimated k1 and k3 increased as the glucose concentration in the culture medium decreased, and this finding did not match the corresponding messenger RNA expression. CONCLUSION: The CIMR system captures dynamic uptake within the cell culture and enables estimation of the cellular pharmacokinetics. PMID- 27363839 TI - Cholangiolocellular carcinoma with rapid progression initially showing abnormally elevated serum alfa-fetoprotein. AB - Cholangiolocellular carcinoma (CoCC) is a rare malignant liver tumor derived from hepatic progenitor cells, which exist in the canals of Hering. We encountered a case of CoCC with an extremely poor clinical course, initially showing abnormally elevated serum alfa-fetoprotein (AFP). A 72-year-old male presented with a liver tumor and abnormally elevated serum AFP levels (16,399 ng/ml). We preoperatively diagnosed hepatocellular carcinoma and performed extended right hepatectomy, after which the serum AFP levels remarkably decreased to 97 ng/ml. Postoperatively, the disease was pathologically diagnosed as CoCC. Furthermore, immunohistochemical pathological findings were alcian blue negative, cytokeratin (CK) 7 partially positive, CK19 positive, hepatocyte paraffin-1 negative, membranous negative for epithelial membrane antigen, and AFP negative. Fifty-five days later, intra- and extrahepatic recurrence developed, and the patient died 65 days after surgery. Although CoCCs show favorable outcomes, these characteristics of our case were not previously reported. It is necessary to accumulate more information on CoCC. PMID- 27363840 TI - Predicting serious complications and high cost of treatment of tooth-knuckle injuries: a systematic literature review. AB - PURPOSE: The tooth-knuckle injury (TKI) is a serious and potentially costly injury seen in orthopaedic practice. The aim was to conduct a systematic literature review on the factors associated with serious complications and high treatment costs in tooth-knuckle injuries. METHODS: MEDLINE, Scopus and CINAHL were used as the literature sources. INCLUSION CRITERIA: Original research papers that reported on factors predicting serious complications and high treatment costs in TKIs were included. There were no restrictions placed on study size, language, study design or date of publication. EXCLUSION CRITERIA: Case studies, case series and review articles were not included. RESULTS: After duplicates were removed, 403 unique studies remained; after titles and abstracts were screened, 48 titles remained and were retrieved in full text. Of these, 14 titles met the inclusion criteria and were included in the data synthesis. Tenosynovitis, septic arthritis, osteomyelitis and residual stiffness were common serious complications occurring in up to 36.3, 70.0, 47.6 and 65.3 % of cases, respectively. Amputation was also common in up to 18.0 % of injuries. Treatment costs were measured by length of hospital stay and the number of debridements required. On average, patients required 3.8-8 days of admission and 1.3-2.7 debridements each. CONCLUSION: Increased time delay from injury to treatment, deeply penetrating injuries, proximal interphalangeal joint (PIPJ) injuries and, possibly, E. corrodens infections were associated with serious complications in TKIs. Delayed treatment, inadequate treatment, PIPJ injuries and deeply penetrating injuries predicted higher treatment costs. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42016029949 ( http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016029949 ). PMID- 27363841 TI - Self-aliquoting micro-grooves in combination with laser ablation-ICP-mass spectrometry for the analysis of challenging liquids: quantification of lead in whole blood. AB - We present a technique for the fast screening of the lead concentration in whole blood samples using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). The whole blood sample is deposited on a polymeric surface and wiped across a set of micro-grooves previously engraved into the surface. The engraving of the micro-grooves was accomplished with the same laser system used for LA-ICP MS analysis. In each groove, a part of the liquid blood is trapped, and thus, the sample is divided into sub-aliquots. These aliquots dry quasi instantly and are then investigated by means of LA-ICP-MS. For quantification, external calibration against aqueous standard solutions was relied on, with iron as an internal standard to account for varying volumes of the sample aliquots. The (208)Pb/(57)Fe nuclide ratio used for quantification was obtained via a data treatment protocol so far only used in the context of isotope ratio determination involving transient signals. The method presented here was shown to provide reliable results for Recipe ClinChek(r) Whole Blood Control levels I-III (nos. 8840-8842), with a repeatability of typically 3 % relative standard deviation (n = 6, for Pb at 442 MUg L(-1)). Spiked and non-spiked real whole blood was analysed as well, and the results were compared with those obtained via dilution and sectorfield ICP-MS. A good agreement between both methods was observed. The detection limit (3 s) for lead in whole blood was established to be 10 MUg L(-1) for the laser ablation method presented here. Graphical Abstract Micro-grooves are filled with whole blood, dried, and analyzed by laser ablation ICP-mass spectrometry. Notice that the laser moves in perpendicular direction with regard to the micro-grooves. PMID- 27363842 TI - Gut bacteria differentially affect egg production in the anautogenous mosquito Aedes aegypti and facultatively autogenous mosquito Aedes atropalpus (Diptera: Culicidae). AB - BACKGROUND: Aedes aegypti and A. atropalpus are related mosquitoes that differ reproductively. Aedes aegypti must blood-feed to produce eggs (anautogenous) while A. atropalpus always produces a first clutch of eggs without blood-feeding (facultatively autogenous). We recently characterized the gut microbiota of A. aegypti and A. atropalpus that were reared identically in the laboratory. Here, we assessed the effects of specific members of the gut microbiota in A. aegypti and A. atropalpus on female fitness including egg production. METHODS: Gnotobiotic A. aegypti and A. atropalpus larvae were colonized by specific members of the gut microbiota. Survival, development time, size and egg production for each treatment was then compared to axenic and conventionally reared larvae. RESULTS: Most species of bacteria we tested supported normal development and egg production by A. aegypti but only one betaproteobacterium, a Comamonas, supported development and egg production by A. atropalpus to equivalent levels as conventionally reared females. Aedes atropalpus females colonized by Comamonas contained similar stores of glycogen and protein as conventionally reared females, whereas females colonized by Aquitalea did not. Small differences in bacterial loads were detected between gnotobiotic and conventionally reared A. aegypti and A. atropalpus, but this variation did not correlate with the beneficial effects of Comamonas in A. atropalpus. CONCLUSIONS: Specific members of the gut microbiota more strongly affected survival, size and egg production by A. atropalpus than A. aegypti. PMID- 27363843 TI - Phase I dose-finding study of monotherapy with atezolizumab, an engineered immunoglobulin monoclonal antibody targeting PD-L1, in Japanese patients with advanced solid tumors. AB - Background Atezolizumab is an engineered immunoglobulin monoclonal antibody that targets the programmed death-1/programmed death-ligand 1 pathway. Methods In this phase I dose-finding study, we assessed the safety, feasibility, pharmacokinetics (PK), and exploratory anti-tumor activity of atezolizumab monotherapy up to 20 mg/kg in Japanese patients with advanced solid tumors who had failed standard therapy or for whom there is no standard therapy. Results Six patients were enrolled and received intravenous atezolizumab every 3 weeks (q3w) at doses of 10 or 20 mg/kg. Tumor types were non-small cell lung cancer (n = 3), melanoma (n = 1), pancreatic cancer (n = 1), and thymic cancer (n = 1). No dose-limiting toxicities were observed. All adverse events (AEs) were grade 1 or 2 in severity. No discontinuations or deaths due to AEs were observed. As of the data cutoff, no partial responses were observed; however, stable disease was observed in all six patients. The maximum mean serum atezolizumab concentration was 220 MUg/mL (SD +/ 21.9), with 10-mg/kg dosing and 536 MUg/mL (SD +/- 49.4) with 20-mg/kg dosing. Three patients were still on treatment, and three of the six had achieved a progression-free survival of >12 months. Conclusions Atezolizumab was well tolerated in Japanese patients at doses up to 20 mg/kg q3w. The safety profile and Cycle 1 serum atezolizumab concentrations were similar to those previously observed in non-Japanese patients. These data support the participation of Japanese patients in ongoing pivotal global studies of atezolizumab. PMID- 27363844 TI - Increased levels of interleukin-33 in gingival crevicular fluids of patients with chronic periodontitis. AB - The purpose of this clinical study is to comparatively investigate the interleukin-33 (IL-33) levels in gingival crevicular fluid (GCF), saliva and plasma of patients with periodontal disease as well as periodontally healthy subjects and the association between these levels and clinical parameters. GCF, saliva and plasma samples were collected from systemically healthy, non-smoker chronic periodontitis patients (CP group, n = 20), gingivitis patients (G group, n = 20) and periodontally healthy control groups (H group, n = 20). Full-mouth clinical periodontal parameters were also recorded. IL-33 levels were determined by ELISA. The total amount of GCF IL-33 was greater in the G and CP groups compared to the H group (p < 0.05). The GCF IL-33 concentration was significantly lower in the CP group than in the H and G groups (p < 0.001). Salivary or plasma IL-33 levels were similar in the study groups. The total amount of GCF IL-33 was positively correlated with the GI, PI and BOP (%) (p < 0.05). Considering the present findings, the increase in total amounts of GCF IL-33 may have a role in the pathogenesis of periodontal disease. PMID- 27363845 TI - Evaluation of Enoxaparin Dosing as a Risk Factor for Bleeding in Lung Transplant Recipients. AB - BACKGROUND: Lung transplant recipients commonly develop complications that lead to anticoagulation. Standard FDA-approved enoxaparin dosing in this population results in a high incidence of above-goal anti-Xa levels, but its association with bleeding remains unclear. OBJECTIVE: To evaluate the association between enoxaparin dosing and bleeding in lung transplant recipients and assess the relationship between dosing and anti-Xa levels. METHODS: We conducted a single center retrospective cohort study of adult lung transplant recipients who received therapeutic enoxaparin between 2000 and 2012 at a tertiary academic center. We dichotomized enoxaparin dosing regimens into standard dose (FDA approved doses with a 10% rounding margin) and reduced dose. Clinicians ordered anti-Xa levels as deemed clinically appropriate. The primary outcome was major bleeding or clinically relevant nonmajor bleeding. RESULTS: Of 222 patients treated with enoxaparin, 33 (14.9%) had bleeding events, of which half (17/33) were major. Bleeding occurred in 25/146 (17.1%) patients who received standard dose enoxaparin versus 8/76 (10.5%) patients who received reduced-dose enoxaparin (P = 0.190). Multiple logistic regression demonstrated an independent association between standard-dose enoxaparin and bleeding, after adjusting for confounders (adjusted odds ratio = 3.04; 95% CI = 1.14-8.10). The median enoxaparin dose in patients with above-goal versus at-goal anti-Xa levels was 0.89 versus 0.76 mg/kg every 12 hours; P = 0.006. However, doses yielding at-goal anti-Xa levels had an interquartile range of 0.67 to 0.90 mg/kg, which overlapped with doses yielding above- and below-goal anti-Xa levels. CONCLUSIONS: Enoxaparin dose reduction and anti-Xa level monitoring can improve drug safety and facilitate individualized dose optimization in lung transplant recipients. PMID- 27363846 TI - Impact of Pharmaceutical Care Interventions on Health-Related Quality-of-Life Outcomes: A Systematic Review and Meta-analysis. AB - OBJECTIVE: To evaluate the impact of pharmaceutical care (PC) interventions on health-related quality of life (HRQoL) and determine sensitivity of HRQoL measures to PC services. DATA SOURCES: MEDLINE, EMBASE, International Pharmaceutical Abstracts, PubMed, Global Health, PsychINFO, CINAHL, and Web of Science (January 2005 to September 2015) were searched. STUDY SELECTION AND DATA EXTRACTION: Original English-language articles were included if PC impact on HRQoL was evaluated and reported using validated HRQoL measures. DATA SYNTHESIS: A total of 31 randomized controlled trials, 9 nonrandomized studies with comparison groups, and 8 before-after studies were included. PC interventions resulted in significant improvement in 1 domain and >=3 domains of HRQoL measures in 66.7% and 27.1% of the studies, respectively. There was a significant improvement in at least 1 domain in 18 of 32 studies using generic and 16 of 21 studies using disease-specific measures. When the Short Form 36 Items Health Survey (SF-36) measure was used, PC interventions had a moderate impact on social functioning (standardized mean difference [SMD] = 0.59; 95% CI = 0.14, 1.04), general health (SMD = 0.36; 95% CI = 0.12, 0.59), and physical functioning (SMD = 0.30; 95% CI = 0.11, 0.48). The pooled data on heart failure-specific (SMD = 0.17; 95% CI = -0.43, 0.09), asthma-specific (SMD = 0.17; 95% CI = -0.03, 0.36), and chronic obstructive pulmonary disease-specific (SMD = -0.09; 95% CI = -0.37, 0.19) measures indicated no significant impact of PC on HRQoL. CONCLUSIONS: PC interventions can significantly improve at least 1 domain of HRQoL. Existing measures may have minimal to moderate sensitivity to PC interventions, with evidence pointing more toward social functioning, general health, and physical functioning of the SF-36 measure. However, evidence generated from current non-PC specific HRQoL measures is insufficient to judge the impact of PC interventions on HRQoL. The development of a suitable HRQoL measure for PC interventions may help generate better evidence for the contribution of pharmacist services to improving HRQoL. PMID- 27363848 TI - Engagement in Play Activities as a Means for Youth in Detention to Acquire Life Skills. AB - This study describes how occupational therapists in a community-based programme, Occupational Therapy Training Program (OTTP), use play activities to facilitate the acquisition of life skills by youth in detention. This pilot study explored the extent of engagement of male and female inmates aged 14 to 18 years old in structured play activities on topics such as interpersonal relationships, self awareness, cultural celebrations and the transition to community. Retrospective analysis of data collected from surveys using the Engagement in OTTP Activities Questionnaire (EOAQ), completed by youth participants at the end of each group session, was used to measure the extent of occupational engagement. Worksheets and artworks produced by OTTP participants during those group sessions were also analysed. The participants reported very high engagement in OTTP. Engagement scores for male participants were higher than those for female participants, and male and female participants had higher engagement scores for different activities. Over 90% of the worksheets and artworks were found to be complete and relevant to the topic of the session. Play activities could be an appropriate way for occupational therapists to encourage youth in detention to acquire life skills. Demographic information and the actual number of participants are unknown because of how the existing data were collected. Future studies examining the potential gender-related preferences for specific topics deserve further investigation as well as research comparing the youth's engagement in OTTP interventions using play activities to other group interventions. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27363847 TI - Deep Genetic Connection Between Cancer and Developmental Disorders. AB - Cancer and developmental disorders (DDs) share dysregulated cellular processes such as proliferation and differentiation. There are well-known genes implicated in both in cancer and DDs. In this study, we aim to quantify this genetic connection using publicly available data. We found that among DD patients, germline damaging de novo variants are more enriched in cancer driver genes than non-drivers. We estimate that cancer driver genes comprise about a third of DD risk genes. Additionally, de novo likely-gene-disrupting variants are more enriched in tumor suppressors, and about 40% of implicated de novo damaging missense variants are located in cancer somatic mutation hotspots, indicating that many genes have a similar mode of action in cancer and DDs. Our results suggest that we can view tumors as natural laboratories for assessing the deleterious effects of mutations that are applicable to germline variants and identification of causal genes and variants in DDs. PMID- 27363849 TI - Regulation of Neurospora crassa cell wall remodeling via the cot-1 pathway is mediated by gul-1. AB - Impairment of the Neurospora crassa Nuclear DBF2-related kinase-encoding gene cot 1 results in pleiotropic effects, including abnormally thick hyphal cell walls and septa. An increase in the transcript abundance of genes encoding chitin and glucan synthases and the chitinase gh18-5, but not the cell wall integrity pathway transcription factor rlm-1, accompany the phenotypic changes observed. Deletion of chs-5 or chs-7 in a cot-1 background results in a reduction of hyperbranching frequency characteristic of the cot-1 parent. gul-1 (a homologue of the yeast SSD1 gene) encodes a translational regulator and has been shown to partially suppress cot-1. We demonstrate that the high expression levels of the cell wall remodeling genes analyzed is curbed, and reaches near wild type levels, when gul-1 is inactivated. This is accompanied by morphological changes that include reduced cell wall thickness and restoration of normal chitin levels. We conclude that gul-1 is a mediator of cell wall remodeling within the cot-1 pathway. PMID- 27363850 TI - [On the anthropological relevance of pain]. AB - Medicine is increasingly being confronted with expectations that it provide more permanent and comprehensive freedom from pain - and the prospect of being pain free is partially even being held out by medical science itself. In our cultural context, there is now the established idea that pain is something that medical science and technology can - and must - "get rid of." This idea is particularly problematic when it comes to chronic pain. Furthermore, it obscures the fact that pain is a significant element of life and one that can have existential meaning. Therefore, it is crucial to reflect on the scope of this wish for medicine to relieve and eliminate pain. PMID- 27363851 TI - Basal Cell Carcinoma of the Nipple-Areola Complex: A Comprehensive Review of the World Literature. AB - BACKGROUND: Basal cell carcinomas (BCCs) usually occur in sun-exposed areas. However, they may also occur-albeit infrequently-in unusual locations, such as the nipple-areola complex. METHODS: Using the PubMed database, an extensive literature search was performed for the following keywords: areola, basal cell carcinoma, and nipple. Papers and references cited in those papers were reviewed to accumulate reports of patients with BCC of the areola and nipple. RESULTS: BCC of the areola and nipple has been described in 55 individuals: 35 males and 20 females. The onset age ranged from 35 to 86 years. The median onset age in males was 61 years, whereas the median onset age in females was 66 years. BCC of the NAC predominantly occurred in Caucasians (75.7%). BCC of the nipple-areola complex (NAC) was observed on the left (54.9%) more frequently than the right (45.1%). Clinical presentation was variable and commonly included scaly or ulcerated plaques and nodules. This tumor was typically associated with the nodular (42.9%) or superficial (30.9%) subtype of BCC. The most common treatment was excision. There were three reported patients who had metastatic disease to their lymph nodes; one of the patients died from his tumor. CONCLUSION: The nipple and areola are uncommon sites of BCC. BCC of the nipple-areola complex is less frequently observed in females (36.4%), as this is more commonly a photo protected site. BCC of the NAC has been considered to behave more aggressively than BCCs at other anatomical sites; however, the BCCs are frequently associated with a non-aggressive histologic subtype. Treatment usually involves complete excision of the BCC. Tumor recurrence was uncommon following successful treatment of the primary neoplasm. PMID- 27363852 TI - Delivery of neoadjuvant chemoradiation for patients with stage II and III rectal cancer is suboptimal. PMID- 27363853 TI - Signing on for dirty work: Taking stock of a public psychiatry project from the inside. AB - As applied anthropologists used to working at arm's length from public psychiatry, we step out of the daily grind to take stock of the challenges of taking on ethnography entrained-harnessed to the implementation of a new program. These include the loss of critical distance, the struggles to negotiate locally viable forms of authority and relevance, the necessity of sustaining a Janus faced relation with principal players, the urgency of seeing time-sensitive information converted into corrective feedback, and the undeniable attraction of being part of "committed work" with game-changing potential. In so doing, we rework the terms of witnessing and revive an old alternative: that documentary dirty work be reclaimed as a variant of public anthropology, one that transforms the work of application from mere afterthought to integral part of the original inquiry. PMID- 27363854 TI - Fetal laser ablation of feeding artery of cystic lung lesions with systemic arterial blood supply. AB - OBJECTIVE: To assess the effectiveness of laser surgery in fetuses with a cystic lung lesion with systemic arterial blood supply (hybrid lung lesion) at risk of perinatal death. METHODS: A cohort of five consecutive fetuses with a large hybrid lung lesion associated with hydrops and/or pleural effusion with severe lung compression was selected for percutaneous ultrasound-guided fetal laser ablation of the feeding artery (FLAFA) before 32 weeks' gestation in a single tertiary national referral center in Queretaro, Mexico. The primary outcomes were survival and need for postnatal surgery. RESULTS: FLAFA was performed successfully in all cases at a median gestational age of 24.9 (range, 24.4-31.7) weeks. After fetal intervention, dimensions in both lungs increased and fluid effusions resolved in all cases. All cases were delivered liveborn at term at a median gestational age of 39.6 (range, 38.0-39.7) weeks, without respiratory morbidity or need for oxygen support, resulting in perinatal survival of 100%. During follow-up, three (60%) cases showed progressive regression of the entire lung mass and did not require postnatal surgery, whereas in two (40%) cases a progressive decrease in size of the mass was observed but a cystic portion of the lung mass persisted and postnatal lobectomy was required. CONCLUSION: In fetuses with large hybrid lung lesions at risk of perinatal death, FLAFA is feasible and could improve survival and decrease the need for postnatal surgery. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27363855 TI - Health professionals cast doubts over personal budgets for pregnant women. PMID- 27363856 TI - Chronic hepatitis C virus infection and the risk for diabetes: a community-based prospective study. AB - BACKGROUND: The association between hepatitis C virus (HCV) infection and the occurrence of type II diabetes remains controversial. Prospective studies are needed to assess its causal temporality. METHODS: A cohort of 21 559 adults enrolled from seven townships in Taiwan during 1991-1992 and followed till the end of 2010. Incident diabetes over a study time period from 2000 to 2010 was ascertained through computerized linkage with the National Health Insurance database and the National Death Certification profiles. Cox's proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Antibodies against HCV (anti-HCV) were tested for all participants, and serum HCV RNA levels were measured for anti-HCV seropositives. RESULTS: During 180 244 person-years of follow-up, there were 1917 incident diabetes cases recorded. The cumulative risk for diabetes was 10.9% for anti-HCV seronegatives and 16.7% for anti-HCV seropositives respectively. The HR for diabetes of anti-HCV seropositivity was 1.53 (95% CI: 1.29-1.81) compared with anti-HCV seronegatives after adjustment for risk predictors. The adjusted HRs were 1.63 (1.31-2.02) for anti-HCV seropositives with positive HCV RNA compared to anti-HCV seronegatives (P<.001). CONCLUSION: Chronic HCV infection was associated with an increased risk for diabetes after adjustment for other risk predictors. PMID- 27363857 TI - Cardiac Involvement in Myotonic Dystrophy Type 2 Patients With Preserved Ejection Fraction: Detection by Cardiovascular Magnetic Resonance. AB - BACKGROUND: Myotonic dystrophy type 2 (DM2) is a genetic disorder characterized by skeletal muscle symptoms, metabolic changes, and cardiac involvement. Histopathologic alterations of the skeletal muscle include fibrosis and fatty infiltration. The aim of this study was to investigate whether subclinical cardiac involvement in DM2 is already detectable in preserved left ventricular function by cardiovascular magnetic resonance. METHODS AND RESULTS: Twenty-seven patients (mean age, 54+/-10 years; 20 females) with a genetically confirmed diagnosis of DM2 were compared with 17 healthy age- and sex-matched controls using a 1.5 T magnetic resonance imaging. For myocardial tissue differentiation, T1 and T2 mapping, fat/water-separated imaging, focal fibrosis imaging (late gadolinium enhancement [LGE]), and (1)H magnetic resonance spectroscopy were performed. Extracellular volume fraction was calculated. Conduction abnormalities were diagnosed based on Groh criteria. LGE located subepicardial basal inferolateral was detectable in 22% of the patients. Extracellular volume was increased in this region and in the adjacent medial inferolateral segment (P=0.03 compared with healthy controls). In 21% of patients with DM2, fat deposits were detectable (all women). The control group showed no abnormalities. Myocardial triglycerides were not different in LGE-positive and LGE-negative subjects (P=0.47). Six patients had indicators for conduction disease (60% of LGE-positive patients and 12.5% of LGE-negative patients). CONCLUSIONS: In DM2, subclinical myocardial injury was already detectable in preserved left ventricular ejection fraction. Extracellular volume was also increased in regions with no focal fibrosis. Myocardial fibrosis was related to conduction abnormalities. PMID- 27363858 TI - Targeting the Heart for Risk Assessment in Myotonic Dystrophy: An Application for Cardiac Magnetic Resonance. PMID- 27363859 TI - Depressive symptoms of house-poor persons: Korean panel data evidence. AB - BACKGROUND: There are no studies researching the relationship between house-poor persons and mental health. Therefore, this study aimed to investigate the relationship between house-poor status and depressive symptoms. AIM: To examine the relationship between the house-poor and depressive symptoms according to household income. METHODS: Data from the Korean Welfare Panel Study were used. House-poor were defined as people having possession with over 10% house-related interest in disposable income. About 7,565 participants over the age of 19 years were followed up from 2011 to 2013. The generalized estimating equations were used for analysis. RESULTS: Individuals with more house-related debt showed increasingly higher depression scores (possession with under 5% related debt to disposable income beta = 0.2024, p = .1544; under 10% beta = 0.7030, p = .0008; over 10% beta = 1.3207, p < .0001). Individuals possessing houses with over 10% ratio of house-related debts to disposable income had higher depression scores than individuals without house ownership (no possession beta = 0.8927, p < .0001). CONCLUSION: Individuals without houses and individuals owning houses with higher percentages of house-related interests showed higher levels of depressive symptoms. Therefore, this study affirmed that the importance of considering the most vulnerable groups in addressing the mental health of individual. PMID- 27363860 TI - Building capacity for community mental health care in rural Malawi: Findings from a district-wide task-sharing intervention with village-based health workers. AB - BACKGROUND: The mental health 'treatment gap' is at its widest in low-resource countries where the vast majority of its people have no access to mental health services and where developing effective models of primary mental health care that can expand from research pilot sites to large-scale population-based services is a major research and practice imperative. AIM: The Mental Health in Zomba initiative builds upon an earlier pilot project to establish and sustain a district-wide scale-up of a village-based health workers' mental health task sharing intervention in Southern Malawi across a population of more than 600,000 people. METHODS: The article describes the development, implementation and structured evaluation of the impact of this task-sharing initiative. RESULTS: Results from an examination of the care for 240 consecutive attendees show how the village-based workers recognised and responded to the needs of people experiencing both common and severe mental health problems and how they facilitated 850 mental health promotion events to more than 40,000 people within their communities. CONCLUSION: A new and essential district-wide tier of mental health service was established at the crucial intersection between health centre and the community. Within the socio-cultural context of rural Malawi with its diverse explanatory models for psychological distress, the approach of the village-based health worker was found to be both credible and practical in meeting the needs of the population and therefore responding to both the 'supply' and 'demand' elements of the mental health treatment gap. PMID- 27363861 TI - Dissection of the qTGW1.1 region into two tightly-linked minor QTLs having stable effects for grain weight in rice. AB - BACKGROUND: Most agronomical traits of crop species are complex traits controlled by multiple genes and affected by environmental factors. While considerable efforts have been made to fine-map and clone major quantitative trait loci (QTLs) for yield-related traits in rice, it is not until recently that the attention has been paid to minor QTLs. Following previous dissection of QTLs for grain weight and grain size in a 12-Mb interval on the long arm of chromosome 1 in rice, this study targeted at one putative QTL region for a more precise mapping and for analyzing the genotype-by-environment interaction of minor QTLs. RESULTS: Four BC2F10 plants of the indica rice cross ZS97///ZS97//ZS97/MY46 were selected. They carried overlapped heterozygous segments that jointly covered the entire putative region for qTGW1.1 detected previously. Four sets of near isogenic lines (NILs) were developed from selfing progenies of the four plants. Each NIL set consisted of 32 ZS97 homozygous lines and 32 MY46 homozygous lines that differed in the corresponding heterozygous region. They were grown in two locations having distinct ecological conditions and measured for 1000-grain weight, grain length and grain width. Two QTLs were separated in an 835.2-kb interval flanked by DNA markers Wn28447 and RM11569. They both showed consistent effects across the two environments. The qTGW1.1a located within the 120.4-kb interval Wn28447 - RM11543 significantly affect all the three traits with the enhancing allele derived from ZS97, showing a stronger influence on grain weight than on grain length and width. The qTGW1.1b located in the 521.8-kb interval RM11554 - RM11569 significantly affect grain weight and length with the enhancing allele derived from MY46, having a stronger influence on grain length than on grain weight. Consistent performance of the two QTLs was confirmed in a validation experiment using five NIL-F2 populations segregated for either qTGW1.1a or qTGW1.1b. CONCLUSION: Separation of closely-linked QTLs having small effects is achievable in the absence of major-QTL segregation. Minor QTLs for complex traits could act consistently in diverse environments, offering the potential of pyramiding beneficial alleles of multiple minor QTLs through marker-assisted selection. PMID- 27363863 TI - Associations between bedtime and nighttime parenting and infant cortisol in the first year. AB - We examined how maternal care within the bedtime and nighttime contexts influences infant cortisol levels and patterning. Eighty-two mothers (Mage = 29.4 years) and infants participated in a longitudinal study when infants were 3, 6, and 9 months old. At each time point, bedtime and nighttime parenting were recorded and infant cortisol at bedtime and the following morning was analyzed. Multilevel model analyses showed that infants had lower cortisol levels when mothers were more emotionally available at bedtime, and infants whose mothers responded more often to their non-distressed cues had lower cortisol levels on average. Less co-sleeping and more maternal responses to infant distress were linked to healthier cortisol patterning. By shedding light on parenting qualities and behaviors that influence infant cortisol, these results indicate avenues for intervention and suggest the utility of studying parenting in infant sleep contexts. PMID- 27363862 TI - Inflammation and emphysema in cigarette smoke-exposed mice when instilled with poly (I:C) or infected with influenza A or respiratory syncytial viruses. AB - BACKGROUND: The length of time for cigarette smoke (CS) exposure to cause emphysema in mice is drastically reduced when CS exposure is combined with viral infection. However, the extent of inflammatory responses and lung pathologies of mice exposed to CS and infected with influenza A virus (IAV), respiratory syncytial virus (RSV), or treated with the viral derivative dsRNA (polyinosine polycytidylic acid [poly (I:C)] have not been compared. METHODS: Mice were exposed to CS or filtered air for 4 weeks and received a single dose of vehicle, AV, or RSV infection and extent of inflammation and emphysema was evaluated 14 d later. In another set of experiments, mice were instilled with poly (I:C) twice a week during the third and fourth weeks of CS exposure and immediately analyzed for extent of inflammation and lung pathologies. RESULTS: In CS-exposed mice, inflammation was characterized mainly by macrophages, lymphocytes, and neutrophils after IAV infection, mainly by lymphocytes, and neutrophils after RSV infection, and mainly by lymphocytes and neutrophils after poly (I:C) instillations. Despite increased inflammation, extent of emphysema by poly (I:C) was very mild; but was robust and similar for both IAV and RSV infections with enhanced MMP-12 mRNA expression and TUNEL positivity. Both IAV and RSV infections increased the levels of IL-17, IL-1beta, IL-12b, IL-18, IL-23a, Ccl-2, Ccl-7 mRNAs in the lungs of CS-exposed mice with IAV causing more increases than RSV. CONCLUSION: CS-induced inflammatory responses and extent of emphysematous changes differ depending on the type of viral infection. These animal models may be useful to study the mechanisms by which different viruses exacerbate CS-induced inflammation and emphysema. PMID- 27363865 TI - Pediatric coronary CTA using phenylephrine to lower heart rate. PMID- 27363864 TI - Outcomes after resection of occupational cholangiocarcinoma. AB - BACKGROUND: Cholangiocarcinoma caused by exposure to 1,2-dichloropropane and/or dichloromethane is recognized as occupational cholangiocarcinoma. The aim of this study was to investigate the outcomes after resection of occupational cholangiocarcinoma to establish a treatment strategy for this disease. METHODS: Clinicopathological findings and outcomes after surgical intervention in 20 patients with occupational cholangiocarcinoma were investigated. RESULTS: Of 20 the patients, curative resection was performed in 16 patients. Three patients underwent radiation at the stump of the bile ducts. Adjuvant chemotherapy was performed in 12 patients. Biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and/or chronic bile duct injury was detected in most subjects. Intraabdominal infection developed after surgery in nine patients. Cholangiocarcinoma recurred in 12 of the 20 patients. The recurrent tumors in five patients developed at a different part of the bile duct from the primary tumor and a second resection was performed in four of these five patients. CONCLUSIONS: The incidence of postoperative complications including intraabdominal infection was high in patients with occupational cholangiocarcinoma. Multicentric recurrence occurred not infrequently after surgery because the bile ducts had a high potential for the development of carcinoma. The aggressive treatment including second resection for the multicentric recurrence appeared to be effective. PMID- 27363866 TI - Impact of comorbid mental health needs on racial/ethnic disparities in general medical care utilization among older adults. AB - OBJECTIVE: The objective is to apply the Institute of Medicine definition of healthcare disparities in order to compare (1) racial/ethnic disparities in general medical care use among older adults with and without comorbid mental health need and (2) racial/ethnic disparities in general medical care use within the group with comorbid mental health need. METHODS: Data were obtained from the Medical Expenditure Panel Survey (years 2004-2012). The sample included 21,263 participants aged 65+ years (14,973 non-Latino Caucasians, 3530 African Americans, and 2760 Latinos). Physical illness was determined by having one of the 11 priority chronic health illnesses. Comorbid mental health need was defined as having one of the chronic illnesses plus a Kessler-6 Scale >12, or two-item Patient Health Questionnaire >2. General medical care use refers to receipt of non-mental health specialty care. Two-part generalized linear models were used to estimate and compare general medical care use and expenditures among older adults with and without a comorbid mental health need. RESULTS: Racial/ethnic disparities in general medical care expenditures were greater among those with comorbid mental health need compared with those without. Among those with comorbid mental health need, non-Latino Caucasians had significantly greater expenditures on prescription drug use than African-Americans and Latinos. CONCLUSIONS: Expenditure disparities reflect differences in the amount of resources provided to African-Americans and Latinos compared with non-Latino Caucasians. This is not equivalent to disparities in quality of care. Interventions and policies are needed to ensure that racial/ethnic minority older adults receive equitable services that enable them to manage effectively their comorbid mental and physical health needs. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27363867 TI - Prevalence and Risk Factors of Voice Problems Among Primary School Teachers in India. AB - OBJECTIVES: Teachers are more prone to develop voice problems (VPs) when compared with other professional voice users. The aim of present study was to investigate the prevalence and risk factors of VPs among primary school teachers in India. STUDY DESIGN: Epidemiological cross-sectional survey. METHODS: Self-reporting questionnaire data were collected from 1082 teachers. RESULTS: Out of 1082 teachers who participated in the present study, 188 teachers reported VPs that account for a prevalence rate of 17.4%. Tired voice after long hours of talking was the most frequently reported symptom, followed by sore/dry throat, strain in voice, neck muscle tension, and difficulty in projecting voice. The adjusted odds ratio values showed number of years of teaching, high background noise levels in the classroom, experiencing psychological stress while teaching classes, improper breath management (holding breath while speaking), poor focus of the tone (clenching jaw/teeth while speaking), upper respiratory tract infection, thyroid problems, and acid reflux as significant risk factors for the development of VPs in the current cohort of teachers. CONCLUSIONS: Current results suggest that teachers develop VPs due to multiple risk factors. These factors may be either biological, psychomotor, or environment-related factors. A holistic approach (which could include educating teachers about voice care during their training, and if they develop VP during their career, then managing the VP by taking into consideration different risk factors) addressing all these factors needs to be adopted to prevent VPs in primary school teachers. PMID- 27363868 TI - Is There a Dirty Side to Personal Care Products? PMID- 27363869 TI - Endocrine Affairs of the Heart. PMID- 27363870 TI - Disinhibiting an Inhibitor: Genetic Engineering Leads to Improvements in Recombinant Inhibin A Production. PMID- 27363873 TI - First report of severe acute otitis media caused by Campylobacter rectus and review of the literature. AB - Campylobacter rectus is a member of the human oral flora and is associated with periodontal disease. We report the first case of severe acute otitis media (AOM) due to C. rectus in a previous healthy 15-year-old boy, which was confirmed by 16S ribosomal RNA gene sequencing. C. rectus is a possible causative pathogen of AOM. PMID- 27363874 TI - Diagnostic aids: the Surgical Sieve revisited. AB - BACKGROUND: Diagnostic errors are well documented in the literature and emphasise the need to teach diagnostic skills at an early stage in medical school to create effective and safe clinicians. Hence, there may be a place for diagnostic aids (such as the Surgical Sieve) that provide a framework for generating ideas about diagnoses. With repeated use of the Surgical Sieve in teaching sessions with students, and prompted by the traditional handheld wheels used in antenatal clinics, we developed the Compass Medicine, a handheld diagnostic wheel comprising three concentric discs attached at the centre. We report a preliminary study comparing the Surgical Sieve and the Compass Medicine in generating differential diagnoses. METHODS: A total of 48 third-year medical students from Cardiff University participated in a study aimed at measuring the efficacy of diagnostic aids (Surgical Sieve and Compass Medicine) in generating diagnoses. We quantified the effect each aid had on the number of diagnoses generated, and compared the size of the effect between the two diagnostic aids. There may be a place for diagnostic aids that provide a framework for generating ideas about diagnoses RESULTS: The study suggests that both diagnostic aids prompted users to generate a greater number of diagnoses, but there was no significant difference in the size of effect between the two diagnostic aids. DISCUSSION: We hope that our study with diagnostic aids will encourage the use of robust tools to teach medical students an easily visualised framework for diagnostic thinking. PMID- 27363875 TI - Erratum. PMID- 27363876 TI - Erratum. PMID- 27363877 TI - Erratum. PMID- 27363878 TI - Psoriasis Trends and Practice Gaps. AB - The present article addresses several high-impact practice gaps affecting psoriatic patients, current practices, the barriers that prevent the delivery of optimal care, and recommendations to improve patient outcomes. Discussions of treatment, cardiovascular risk factor screening, psoriatic arthritis screening, and biologics are included. Finally, an overview of current resident exposure to psoriatic care and recommendations for improvements in resident education are made. PMID- 27363879 TI - Practice and Educational Gaps in Lupus, Dermatomyositis, and Morphea. AB - Patients with skin-predominant lupus erythematosus, dermatomyositis, and morphea should be evaluated, treated, and followed by dermatologists who can take primary responsibility for their care. Many academic centers have specialized centers with dermatologists who care for these patients. Patients with skin-predominant lupus erythematosus should be followed regularly with laboratory tests to detect significant systemic disease. Antibody tests can help determine the risks for individual patients. Patients with morphea rarely progress to systemic disease, but therapies can be helpful in treating and preventing progression of disease. PMID- 27363880 TI - Practice and Educational Gaps in Blistering Disease. AB - Treatment of autoimmune patients can be challenging and rewarding. These patients often remain undiagnosed for prolonged periods of time or underdiagnosed without immunologic confirmation, resulting in significant morbidity. The most important principle in management of autoimmune bullous disease is to halt blistering activity while minimizing side effects of medications, especially those caused by corticosteroids. Judicious use of systemic steroids and steroid-sparing agents are essential tools in the management of these patients. Rituximab and intravenous immunoglobulin are playing increasingly important and earlier roles in management. Understanding of and surveillance for drug side effects are critical in long-term management. PMID- 27363881 TI - Practice Gaps in Pruritus. AB - There are several practice gaps in the evaluation and management of itch. These gaps include a dearth of objective measures of itch, infrequent use of validated patient-reported outcomes for itch, non-evidence-based treatment, and lack of consensus about the ideal workup for generalized itch. The present article reviews these gaps and presents potential solutions. PMID- 27363882 TI - Contact Dermatitis: Practice Gaps and Challenges. AB - Patch testing remains the criterion standard for diagnosing allergic contact dermatitis. A thorough and detailed history, proper selection of allergens and testing procedure, as well as education of patients are all key parts of this procedure and important in the successful management of those suspected of having allergic contact dermatitis. Physicians must also be aware of the continual introduction of new chemicals that are potential new allergens and adjust screening allergens appropriately. PMID- 27363883 TI - Clinical and Educational Gaps in Diagnosis of Nail Disorders. AB - Dermatologists care for skin, hair, and nails, yet many dermatologists find nail disorders challenging. Practice gaps in knowledge, skill, and attitude in clinical practice and resident education are sometimes impediments to timely medical and surgical diagnosis of nail disorders. Limited resident exposure to diagnosis and management of complicated nail disorders and lack of experience performing diagnostic and surgical procedures impairs progress toward surmounting these gaps. PMID- 27363884 TI - Practice and Educational Gaps in Dermatology: Disorders of the Hair. AB - Clinical practice gaps exist in the care of hair patients. Attitude gaps include a relative lack of dermatologists interested in caring for patients with hair complaints, a potential underestimation of the effect of hair disorders on the quality of patients' lives, and potential failure to recognize the presentation of body dysmorphic disorder among patients with hair complaints. Knowledge gaps regarding the prevalence and presentation of hair loss disorders may lead to a delay in diagnosis and treatment of hair patients. Skill gaps in physical examination, particularly with dermoscopy of the scalp and hair, may affect the care of hair patients. PMID- 27363885 TI - Infectious Disease Practice Gaps in Dermatology. AB - The article highlights different educational and practice gaps in infectious diseases as they pertain to dermatology. These gaps include the use of antibiotics in relation to atopic dermatitis and acne vulgaris, treatment of skin and soft tissue infection, and diagnosis and treatment of onychomycosis. In addition, practice gaps related to use of imiquimod for molluscum contagiosum, risk of infections related to immunosuppressive medications and rates of vaccination, and the use of bedside diagnostics for diagnosing common infections were discussed. PMID- 27363886 TI - Practice and Educational Gaps in Abnormal Pigmentation. AB - Dyschromia refers to abnormal pigmentation and is one of the most common diagnoses in dermatology. However, there are many educational and practice gaps in this area, specifically in melasma, postinflammatory hyperpigmentation, and vitiligo. This article aims to review the gold standard of care for these conditions as well as highlight common educational and practice gaps in these areas. Finally, possible solutions to these gaps are addressed. PMID- 27363887 TI - Practice and Educational Gaps in Genodermatoses. AB - In the past 2 decades, there has been enormous progress in determining the molecular bases of genodermatoses. This progress has expanded the interface between dermatology and genetics. Integration of clinical and molecular data has simplified disease classification and highlighted relationships among conditions. However, the recent explosion in genetic knowledge has not yet been fully incorporated into clinical dermatology practice or dermatology resident education. This article highlights strategies to overcome barriers and correct practice and educational gaps, enhancing the ability of dermatologists to diagnose, counsel, evaluate, and treat patients and families affected by genodermatoses. PMID- 27363888 TI - Practice Gaps: Drug Reactions. AB - The term "drug reactions" is relevant to dermatology in three categories of reactions: cutaneous drug reactions without systemic features, cutaneous drug reactions with systemic features, and systemic drugs prescribed by the dermatologist with systematic adverse effects. This article uses examples from each of these categories to illustrate several important principles central to drug reaction diagnosis and management. The information presented will help clinicians attain the highest possible level of certainty before making clinical decisions. PMID- 27363889 TI - Practice and Educational Gaps in Radiation Therapy in Dermatology. AB - Guidelines for appropriate use of superficial radiation therapy are based on decades of research; although no formal appropriate use criteria have been developed, they are warranted. Superficial radiation in the outpatient dermatologic setting is the least expensive form of radiation treatment. Although higher cure rates may be possible with Mohs surgery, this should never argue against dermatologists retaining and refining a modality, nor should we limit its use by our successors. Most important, our elderly and infirm patients should continue to benefit from superficial radiation therapy in outpatient dermatologic settings. PMID- 27363890 TI - Practice and Educational Gaps in Surgery for Skin Cancer. AB - Surgery for skin cancer is a major part of clinical dermatology, and the largest single component of dermatologic surgery practice. In general, residency training in dermatology provides comprehensive training in the theory and practice of skin cancer surgery. Practicing dermatologists are similarly expert in this area, and frequently assist other medical and surgical services by managing and coordinating the care of patients with skin cancer. However, there are minor gaps in training and practice that bear scrutiny and are amenable to rectification. This article defines the current practice in surgical treatment of skin cancers by dermatologists, gaps in practice, and mechanisms to improve current surgical practice. PMID- 27363891 TI - Practice and Educational Gaps in Cosmetic Dermatologic Surgery. AB - This article identifies gaps in the practice of cosmetic dermatology and cosmetics education, and how to overcome these limitations. There is a rapid development of new devices and procedures, with limited data, patient-reported outcomes, and comparative effectiveness research from which to develop best cosmetic practice. There is a need for increased research and funding dedicated to these goals, improved and convenient training for staff to adopt new devices/procedures, and continuous evolution of databases to pool outcome data and develop outcome sets. Resident education can be improved by dedicated resident cosmetic clinics, didactic teaching from visiting professors, attendance of cosmetic dermatology courses and meetings, and encouraging postresidency training. PMID- 27363892 TI - Practice and Educational Gaps in Light, Laser, and Energy Treatments. AB - This article discusses current practice in laser dermatology, the gaps in practice, and recommendations for improvement. As is the case with other areas of cosmetic dermatology, there is a rapid development of new laser and light devices with limited epidemiologic data available to inform best practice. The high fixed cost associated with new laser devices, limited space available in some practices, and inconsistent training may limit the adoption of needed therapies. Improving research in this area; training opportunities for physicians, residents, and staff; and cost-effective laser/light device rentals programs could improve quality of current practice. PMID- 27363893 TI - Practice Gaps in Dermatology: Melanocytic Lesions and Melanoma. AB - Early detection remains the most important strategy to reduce melanoma mortality. The identification and evaluation of new or changing skin lesions are important components of melanoma screening and are best performed today using complementary noninvasive imaging technologies, such as total body photography (TBP), dermoscopy, sequential digital dermoscopic imaging (SDDI), and reflectance confocal microscopy (RCM). Despite strong evidence showing that these screening techniques improve diagnostic accuracy for melanoma, they are not widely used by dermatologists. In this practice gaps review, the authors highlight the use, evidence, and rationale for TBP, dermoscopy, SDDI, and RCM. PMID- 27363894 TI - Practice Gaps and Training Gaps: Delineating What We Need to Fix. PMID- 27363895 TI - Wnt activity is associated with cementum-type transition. AB - BACKGROUND AND OBJECTIVE: Cellular and acellular cementum and the cells that form them are postulated to have different characteristics, and the relationship between these two tissues is not well understood. Based on the hypothesis that Wnt signaling is involved in the determination of cementum type, we examined Wnt activity along the tooth root and analyzed cementum formation in genetic mutant models. MATERIAL AND METHODS: We generated mutant models with Wnt signaling upregulation (OC Catnblox(ex3)/+ ), downregulation (OC Wlsfl/fl ), and a compound mutant (Enpp1asj/asj ;OC Catnblox(ex3)/+ ) to compare cementum apposition patterns of ectonucleotide diphosphatase/phosphodiesterase (Enpp1) mutant (Enpp1asj/asj ). The analysis of structural morphology and histology was performed with hematoxylin and eosin and immunohistochemical staining and scanning electron microscopy. RESULTS: The cementum type of upper apical region of tooth roots in the molar is altered from the cellular form at the initial stage to the acellular form at the late stage of cementum formation. However, the basal part of this apical region is not altered and retains cellular cementum characters with strong Wnt activity. In the genetic mutant models for Wnt upregulation, cellular cementum is formed at the cervical region instead of acellular cementum. However, Enpp1 mutant mice have clearly different characteristics with cellular-type cementum even with dramatically increased cervical cementum matrix. In addition, we found that acellular-type formation could be altered into cellular-type formation by analyzing Wnt upregulation and compound mutant models. CONCLUSIONS: Cementum type is not determined by its specific location and could be transformed with Wnt activity during cementum formation. PMID- 27363896 TI - Quantification of probe-sample interactions of a scanning thermal microscope using a nanofabricated calibration sample having programmable size. AB - We report a method for quantifying scanning thermal microscopy (SThM) probe sample thermal interactions in air using a novel temperature calibration device. This new device has been designed, fabricated and characterised using SThM to provide an accurate and spatially variable temperature distribution that can be used as a temperature reference due to its unique design. The device was characterised by means of a microfabricated SThM probe operating in passive mode. This data was interpreted using a heat transfer model, built to describe the thermal interactions during a SThM thermal scan. This permitted the thermal contact resistance between the SThM tip and the device to be determined as 8.33 * 10(5) K W(-1). It also permitted the probe-sample contact radius to be clarified as being the same size as the probe's tip radius of curvature. Finally, the data were used in the construction of a lumped-system steady state model for the SThM probe and its potential applications were addressed. PMID- 27363898 TI - Neointimal coverage on acute vessel wall injuries after stenting: 6-month follow up study. AB - BACKGROUND: Stent implantation often creates local vessel wall injuries which can be characterized in detail by optical coherence tomography (OCT). Little is known about the neointimal coverage at these areas. We aimed to evaluate neointimal coverage of vessel wall injuries area associated with stent implantation. METHODS: We retrospectively selected patients implanted with sirolimus-eluting stents (SES) having excellent OCT images immediately after stent implantation and at the 6-month follow-up. All OCT cross-sectional images were divided into three groups: intra-stent tissue prolapse (ISTP) areas, intra-stent dissection flaps (ISDF) areas, and non-injuried areas. The neointimal coverage in included sections was evaluated at 6 months follow-up. RESULTS: Finally, 1690 cross sectional images in 74 stents were analyzed totally. Among which, 240 images (14.20%) involved ISTP areas, 124 images (7.34%) at ISDF areas, and 1326 images (78.46%) at non-injuried areas. All ISTP and ISDF were disappeared at six months follow-up, Neointimal thickness at ISTP and ISDF areas increased significantly compared to the one in non-injuried areas (97.4+/-40.3MUm vs. 68.4+/-47.6MUm, P<0.001; 92.7+/-49.8MUm vs. 68.4+/-47.6MUm, P<0.001). Mean neointimal area of ISTP and ISDF areas was almost the same (0.8+/-0.3 mm2), which both had a significant difference compared to mean neointimal area (0.6+/-0.4mm2) at non injuried areas (p1<0.001, p2=0.006). CONCLUSIONS: Intra-stent tissue prolapse and intra-stent dissection flaps have benign clinical course up to 6 months. The areas with these local complications, however, have greater neointimal hyperplasia compared to the non-injuried areas. PMID- 27363897 TI - Novel role of cortactin in G protein-coupled receptor agonist-induced nuclear export and degradation of p21Cip1. AB - Monocyte chemotactic protein 1 (MCP1) stimulates phosphorylation of cortactin on Y421 and Y446 residues in a time-dependent manner and phosphorylation at Y446 but not Y421 residue is required for MCP1-induced CDK-interacting protein 1 (p21Cip1) nuclear export and degradation in facilitating human aortic smooth muscle cell (HASMC) proliferation. In addition, MCP1-induced cortactin tyrosine phosphorylation, p21Cip1 degradation and HASMC proliferation are dependent on Fyn activation. Upstream to Fyn, MCP1 stimulated C-C chemokine receptor type 2 (CCR2) and Gi/o and inhibition of either one of these molecules using their specific antagonists or inhibitors attenuated MCP1-induced cortactin tyrosine phosphorylation, p21Cip1 degradation and HASMC proliferation. Cortactin phosphorylation at Y446 residue is also required for another G protein-coupled receptor (GPCR) agonist, thrombin-induced p21Cip1 nuclear export and its degradation in promoting HASMC proliferation. Quite interestingly, the receptor tyrosine kinase (RTK) agonist, platelet-derived growth factor-BB (PDGF-BB) induced p21Cip1 degradation and HASMC proliferation do not require cortactin tyrosine phosphorylation. Together, these findings demonstrate that tyrosine phosphorylation of cortactin at Y446 residue is selective for only GPCR but not RTK agonist-induced nuclear export and proteolytic degradation of p21Cip1 in HASMC proliferation. PMID- 27363899 TI - Optimal stimulation during monitored thyroid surgery: EMG response characteristics in a porcine model. AB - OBJECTIVES: To compare electromyography (EMG) characteristics of the external branch of superior laryngeal nerve (EBSLN), recurrent laryngeal nerve (RLN), and vagus nerve (VN) evoked with different stimulation probes/dissectors during monitored thyroid surgery. STUDY DESIGN: Experimental porcine model. METHODS: In five piglets (10 EBSLNs/RLNs/VNs), laryngeal EMG was recorded by endotracheal tube surface electrodes with stimulation using five monopolar probes (group I), three bipolar probes (group II), and two stimulation dissectors (group III). The detectable EMG response (DER) was defined as > 100 MUV and was obtained with these different probes/dissectors. Electromyography parameters, stimulus-response curve, and distance-sensitivity results were compared. RESULTS: All stimulation probes/dissectors evoked typical EMG waveforms from the EBSLN/RLN/VN with 1 mA current. A stimulus-response curve with increasing EMG amplitude with increase in stimulating current was noted, with the maximum EMG elicited by group I/III probes/dissectors at < 1 mA and at a higher current for group II probes. All groups recorded lower evoked EMG amplitudes when the nerve was stimulated with overlying fascia or when probe/dissector to nerve distance was greater. The mean amplitude decreased by 11%/33%/13% in group I/II/III probes/dissectors when stimulating nerves covered by fascia versus nerves dissected free of overlying fascia. The rate of obtaining DER at 1- or 2-mm distance was significantly higher in group I than in group II/III probes/dissectors (P < 0.001). Latency did not change with any of the stimulation probes/dissectors or trials. CONCLUSION: Monopolar, bipolar probes, and newer stimulation dissectors all provided valid evoked VN/RLN/EBSLN waveforms. They have different functional sensitivity profiles and vary when stimulating with fascia and at a distance from the nerve. Selection of a stimulation probe/dissector for nerve monitoring can be based on the stimulation characteristics, the intended nerve monitoring application, and the surgeon's preference. LEVEL OF EVIDENCE: N/A. Laryngoscope, 127:998-1005, 2017. PMID- 27363900 TI - Protolichesterinic acid enhances doxorubicin-induced apoptosis in HeLa cells in vitro. AB - AIM: The aim of this study was to investigate the effect of protolichesterinic acid, a lichen secondary metabolite, on anti-proliferative activity of doxorubicin in three human cancer cell lines, HeLa, SH-SY5Y and K562 cells. MAIN METHODS: The data obtained from MTT assays, performed on cells treated with protolichesterinic acid and doxorubicin alone and in combination, were analysed by the median-effect method as proposed by Chou and Talalay and the Bliss independence model. Apoptosis rate was evaluated by fluorescence microscopy, caspase-3, 8 and 9 activities were detected by spectrofluorimetric analysis and protein expression of Bim, Bid, Bax and Mcl-2 was analysed by Western blotting. The interaction of protolichesterinic acid with thioesterase domain of human fatty acid synthase (hFAS) was investigated by a molecular docking study. KEY FINDINGS: The in vitro activity of doxorubicin against HeLa cancer cell line, but not against SH-SY5Y and K562 cells, was synergically increased by protolichesterinic acid. The increased cytotoxicity caused by protolichesterinic acid in HeLa cells was due to a pro-apoptotic effect and was associated to caspase-3, 8 and 9 activation. The simultaneous treatment for 24h with protolichesterinic acid plus doxorubicin caused an increase of Bim protein expression and the appearance of cleaved form of Bid protein. The molecular modelling analysis showed that protolichesterinic acid seemed to behave as a competitive inhibitor of hFAS. SIGNIFICANCE: These results suggest that protolichesterinic acid could be envisaged as an useful tool against certain types of tumor cells in combination with anticancer drugs. PMID- 27363901 TI - Analysis of the effect of sentiment analysis on extracting adverse drug reactions from tweets and forum posts. AB - OBJECTIVE: The abundance of text available in social media and health related forums along with the rich expression of public opinion have recently attracted the interest of the public health community to use these sources for pharmacovigilance. Based on the intuition that patients post about Adverse Drug Reactions (ADRs) expressing negative sentiments, we investigate the effect of sentiment analysis features in locating ADR mentions. METHODS: We enrich the feature space of a state-of-the-art ADR identification method with sentiment analysis features. Using a corpus of posts from the DailyStrength forum and tweets annotated for ADR and indication mentions, we evaluate the extent to which sentiment analysis features help in locating ADR mentions and distinguishing them from indication mentions. RESULTS: Evaluation results show that sentiment analysis features marginally improve ADR identification in tweets and health related forum posts. Adding sentiment analysis features achieved a statistically significant F-measure increase from 72.14% to 73.22% in the Twitter part of an existing corpus using its original train/test split. Using stratified 10*10-fold cross-validation, statistically significant F-measure increases were shown in the DailyStrength part of the corpus, from 79.57% to 80.14%, and in the Twitter part of the corpus, from 66.91% to 69.16%. Moreover, sentiment analysis features are shown to reduce the number of ADRs being recognized as indications. CONCLUSION: This study shows that adding sentiment analysis features can marginally improve the performance of even a state-of-the-art ADR identification method. This improvement can be of use to pharmacovigilance practice, due to the rapidly increasing popularity of social media and health forums. PMID- 27363902 TI - Cancer Stem Cells, Epithelial to Mesenchymal Markers, and Circulating Tumor Cells in Small Cell Lung Cancer. AB - BACKGROUND: Small cell lung cancer (SCLC) has a poor prognosis, and even with localized (limited) disease, the 5-year survival has only been around 20%. Elevated levels of circulating tumor cells (CTCs) have been associated with a worse prognosis, and markers of cancer stem cells (CSCs) and epithelial to mesenchymal transition have been associated with increased chemoresistance and metastatic spread in SCLC. PATIENTS AND METHODS: The biopsy specimens of 38 SCLC patients were used for marker evaluation by immunohistochemistry. The markers for CSCs were CD44 and SOX2. The markers for epithelial to mesenchymal transition were E-cadherin, epithelial cell adhesion molecule, cytokeratins 8, 18, and 19, vimentin, and c-MET. Staining was scored as low (weak) or high (strong) intensity for SOX2, epithelial cell adhesion molecule, cytokeratins 8, 18, and 19, and c MET and using the immunoreactive score for CD44, E-cadherin, and vimentin, expressed as low or high expression. RESULTS: High expression of c-MET (c-METH) and low expression of E-cadherin (E-cadL) showed a trend toward a better prognosis (P = .07 and P = .09, respectively). The combination of c-METH and E cadL resulted in significantly better survival (P = .007). The tested markers were not associated with CTCs, although a trend was seen for c-METHE-cadL (P = .09) with low CTCs. The CSC markers SOX2 and CD44 were not associated with overall survival in this patient cohort. CONCLUSION: SCLC with a mesenchymal-like phenotype (c-METHE-cadL) is associated with longer survival and showed a trend toward lower CTCs. PMID- 27363903 TI - Bioactive packaging using antioxidant extracts for the prevention of microbial food-spoilage. AB - Bioactive food packaging is an innovative approach for the prevention of the growth of food-spoilage microorganisms. Four active extracts from agroindustrial subproducts (Eucalyptus wood, almond shells, corn cobs and grape pomace) with demonstrated antioxidant activity have been investigated for bestowing antimicrobial activity to bioactive packaging. To carry out this evaluation, the antioxidant extracts were tested against five food pathogenic bacteria, namely, Escherichia coli, Pseudomonas aeruginosa, Listeria monocytogenes, Staphylococcus aureus and Salmonella spp. The results obtained showed that all the tested extracts inhibited the growth of all five pathogenic bacteria. From the analysis of the minimal bactericidal concentrations (MBCs), the Eucalyptus wood extract was the most active, being necessary only 2% (v/v) to inhibit Pseudomonas aeruginosa, Listeria monocytogenes, and Staphylococcus aureus, whereas almond shells extract were less active requiring 4% (w/v) to inhibit the growth of Escherichia coli and Pseudomonas aeruginosa and the extract from corn cobs was bactericidal against Escherichia coli and Staphylococcus aureus at a concentration of 4% (w/v). After checking their antimicrobial activity, the antioxidant extracts have been incorporated into sodium alginate films and the maintenance of their antimicrobial properties was confirmed. This work showed that the antioxidant extracts from agroindustrial byproducts exhibited antimicrobial activity and were suitable for incorporation into edible films that could be used in bioactive packaging systems. PMID- 27363904 TI - Tuberculosis Caused by Mycobacterium bovis in a Capybara (Hydrochoerus hydrochaeris). AB - Tuberculosis, associated with Mycobacterium bovis, was diagnosed post mortem in an adult female capybara (Hydrochoerus hydrochaeris), kept at the Pampulha Ecological Park, Belo Horizonte, Brazil, in a large metropolitan area. On post mortem examination, there were numerous firm white nodules scattered throughout all lobes of both lungs. Tissue samples were collected for histological and microbiological examination. Microscopically, the pulmonary nodules were multifocal to coalescing granulomas and intralesional acid-fast bacilli were evident in Ziehl-Neelsen-stained sections of the lung and spleen. Colonies with morphological features of Mycobacterium spp. were isolated from lung samples and conventional polymerase chain reaction (PCR) with genomic DNA from the isolates was positive for M. bovis; sequencing indicated 100% identity with the region of difference 4 (RD4) of M. bovis. In addition, M. bovis DNA was detected in the lung by quantitative PCR. The finding of M. bovis in a capybara indicates a potential public health risk in a zoological collection. PMID- 27363905 TI - First physical evidence for forested environment in the Arctic during MIS 3. AB - Old sedimentological and geochronological records can be preserved underneath the central parts of the continental ice sheets under non-erosive, cold-based subglacial conditions. Organic deposits that predate the last deglaciation are of particular value for the information held on glacial-time climate and environmental conditions. In this study, we present multiproxy data derived from a well-preserved MIS 3 interstadial (55-25 ka ago) organic layer from inside the Arctic Circle in the Finnish Lapland. Biological proxy evidence, namely coming from aquatic plant species, indicates July temperatures as high as 14.4 degrees C, i.e. higher than those of today for the study site. Macrofossil evidence demonstrates for the first time the presence of pines accompanied by tree birch during the MIS 3 interstadial in northern Fennoscandia. These results concur with contemporary insolation model outcomes but contradict with the previous proxy based view of open tundra conditions during the MIS 3. The data suggest that there are highly dynamic interstadial continental ice-sheet dynamics following changes in orbital forcing. Warm climate enabled the establishment of forests on exposed landscape. Moreover, we suggest that in the light of these new data, previous MIS 3 pollen data could be re-interpreted. PMID- 27363921 TI - Alcohol risk drinking, quality of life and health state among patients treated at the Sobering Unit in the emergency department - One year follow-up study. AB - OBJECTIVES: To evaluate impacts of brief intervention on patients' alcohol risk drinking, quality of life and health state after treatment at the Sobering Unit in the emergency department at three months, six months, and one year follow-up. METHODS: This was a quasi-experimental study without control group (one-year follow-up). Alcohol use of patients in emergency department (Sobering Unit) in specialized care in Finland (AUDIT-test), quality of life (EQ-5D-3L) and health state (EQ VAS) at baseline, three months, six months and one year following the brief intervention were analyzed with Wilcoxon Signed-Rank test. RESULTS: The patients' alcohol risk use decreased statistically significantly after the treatment period at the Sobering Unit. The patients' health-related quality of life did not change statistically significantly during three months following the treatment period, whereas a statistically significant increase took place after six months. Self-perceived health status improved statistically significantly between the treatment period and three- and six-month follow up time points. CONCLUSIONS: The study gave some suggestive evidence that a brief intervention could be effective for harmful drinkers or alcohol-dependent patients when used in an emergency department. The Sobering Unit in the emergency department is one solution to encourage patients to pay attention to their alcohol risk drinking. PMID- 27363922 TI - Parameters for abolishing conditioned place preference for cocaine from running and environmental enrichment in male C57BL/6J mice. AB - RATIONALE: Evidence suggests that 4 weeks of voluntary wheel running abolishes conditioned place preference (CPP) for cocaine in male C57BL/6J mice. OBJECTIVES: To determine the duration and timing of exposure to running wheels necessary to reduce CPP, and the extent to which the running per se influences CPP as compared to environmental enrichment without running. METHODS: A total of 239 males were conditioned for 4days twice daily with cocaine (10mg/kg) and then split into 7 intervention groups prior to 4days of CPP testing. Experiment 1 consisted of two groups housed as follows: short sedentary group (SS; n=20) in normal cages for 1 week; the short running group (SR; n=20) with running wheels for 1 week. Experiment 2 consisted of five groups housed as follows; short 1 week of running followed by a 3 week sedentary period (SRS; n=20); a 3 week sedentary period followed by 1 week of running (SSR; n=20); long sedentary group (LS; n=66) in normal cages for 4 weeks; long running group (LR; n=66) with running wheels for 4 weeks; and long environmental enrichment group (EE; n=27) with toys for 4 weeks. RESULTS: Levels of running were similar in all running groups. Both running and environmental enrichment reduced CPP relative to sedentary groups. CONCLUSIONS: Results suggest that the abolishment of cocaine CPP from running is robust and occurs with as low as 1 week of intervention but may be related to enrichment component of running rather than physical activity. PMID- 27363923 TI - Histamine H3 receptor as a potential target for cognitive symptoms in neuropsychiatric diseases. AB - The potential contributions of the brain histaminergic system in neurodegenerative diseases, and the possiblity of histamine-targeting treatments is attracting considerable interests. The histamine H3 receptor (H3R) is expressed mainly in the central nervous system, and is, consequently, an attractive pharmacological target. Although recently described clinical trials have been disappointing in attention deficit hyperactivity disorder (ADHD) and schizophrenia (SCH), numerous H3R antagonists, including pitolisant, demonstrate potential in the treatment of narcolepsy, excessive daytime sleepiness associated with cognitive impairment, epilepsy, and Alzheimer's disease (AD). This review focuses on the recent preclinical as well as clinical results that support the relevance of H3R antagonists for the treatment of cognitive symptoms in neuropsychiatric diseases, namely AD, epilepsy and SCH. The review summarizes the role of histaminergic neurotransmission with focus on these brain disorders, as well as the effects of numerous H3R antagonists on animal models and humans. PMID- 27363924 TI - DBI/ACBP loss-of-function does not affect anxiety-like behaviour but reduces anxiolytic responses to diazepam in mice. AB - Diazepam is well known for its anxiolytic properties, which are mediated via activation of the GABAA receptor. Diazepam Binding Inhibitor (DBI), also called acyl-CoA binding protein (ACBP), is a ubiquitously expressed protein originally identified based on its ability to displace diazepam from its binding site on the GABAA receptor. Central administration of ACBP or its cleaved fragment, commonly referred to as endozepines, induces proconflict and anxiety-like behaviour in rodents. For this reason, ACBP is known as an anxiogenic peptide. However, the role of endogenous ACBP in anxiety-like behaviour and anxiolytic responses to diazepam has not been investigated. To address this question, we assessed anxiety behaviour and anxiolytic responses to diazepam in two complementary loss-of function mouse models including astrocyte-specific ACBP KO (ACBP(GFAP) KO) and whole-body KO (ACBP KO) mice. Male and female ACBP(GFAP) KO and ACBP KO mice do not show significant changes in anxiety-like behaviour compared to control littermates during elevated plus maze (EPM) and open field (OF) tests. Surprisingly, ACBP(GFAP) KO and ACBP KO mice were unresponsive to the anxiolytic effect of a low dose of diazepam during EPM tests. In conclusion, our experiments using genetic ACBP loss-of-function models suggest that endozepines deficiency does not affect anxiety-like behaviour in mice and impairs the anxiolytic action of diazepam. PMID- 27363926 TI - Differential effects of glucocorticoid and mineralocorticoid antagonism on anxiety behavior in mild traumatic brain injury. AB - Mild traumatic brain injuries (TBIs) comprise three-quarters of all TBIs occurring in the United States annually, and psychological symptoms arising from them can last years after injury. One commonly observed symptom following mild TBI is generalized anxiety. Most mild TBIs happen in stressful situations (sports, war, domestic violence, etc.) when glucocorticoids are elevated in the brain at the time of impact, and glucocorticoids have negative effects on neuronal health following TBI. Therefore, blocking glucocorticoid receptors might prevent emergence of anxiety symptoms post-injury. Adult male rats received mifepristone (20mg/kg) or spironolactone (50mg/kg) to block glucocorticoid and mineralocorticoid receptors, respectively, 40min prior to being exposed to acute social defeat stress followed immediately by mild TBI. In defeated rats with concomitant mild TBI, mifepristone restored time spent in the open arms of an elevated plus maze to control levels, demonstrating for the first time that glucocorticoid receptors play a critical role in the development of anxiety after mild TBI. Future treatments could target these receptors, alleviating anxiety as a major side effect in victims of mild TBI sustained in stressful situations. PMID- 27363925 TI - Nicotine-induced behavioral sensitization in an adult rat model of attention deficit/hyperactivity disorder (ADHD). AB - Attention deficit hyperactivity disorder (ADHD) is associated with increased risk of tobacco dependence. Nicotine, the main psychoactive component of tobacco, appears to be implicated in ADHD-related tobacco dependence. However, the behavioral responsiveness to nicotine of the prevalent animal model of ADHD, the spontaneously hypertensive rat (SHR), is currently underinvestigated. The present study examined the activational effects of acute and chronic nicotine on the behavior of adult male SHRs, relative to Wistar Kyoto (WKY) controls. Experiment 1 verified baseline strain differences in open-field locomotor activity. Experiment 2 tested for baseline strain differences in rotational behavior using a Rotorat apparatus. Adult SHR and WKY rats were then exposed to a 7-day regimen of 0.6mg/kg/d s.c. nicotine, or saline, prior to each assessment. A separate group of SHRs underwent similar training, but was pre-treated with mecamylamine, a cholinergic antagonist. Nicotine sensitization, context conditioning, and mecamylamine effects were then tested. Baseline strain differences were observed in open-field performance and in the number of full rotations in the Rotorat apparatus, but not in the number of 90 degrees rotations or direction changes. In these latter measures, SHRs displayed weaker nicotine-induced rotational suppression than WKYs. Both strains expressed nicotine-induced sensitization of rotational activity, but evidence for strain differences in sensitization was ambiguous; context conditioning was not observed. Mecamylamine reversed the effects of nicotine on SHR performance. These findings are consistent with the hypothesis that a reduced aversion to nicotine (expressed in rats as robust locomotion) may facilitate smoking among adults with ADHD. PMID- 27363927 TI - Sexual dimorphisms in swimming behavior, cerebral metabolic activity and adrenoceptors in adult zebrafish (Danio rerio). AB - Sexually dimorphic behaviors and brain sex differences, not only restricted to reproduction, are considered to be evolutionary preserved. Specifically, anxiety related behavioral repertoire is suggested to exhibit sex-specific characteristics in rodents and primates. The present study investigated whether behavioral responses to novelty, have sex-specific characteristics in the neurogenetic model organism zebrafish (Danio rerio), lacking chromosomal sex determination. For this, aspects of anxiety-like behavior (including reduced exploration, increased freezing behavior and erratic movement) of male and female adult zebrafish were tested in a novel tank paradigm and after habituation. Male and female zebrafish showed significant differences in their swimming activity in response to novelty, with females showing less anxiety spending more time in the upper tank level. When fish have habituated, regional cerebral glucose uptake, an index of neuronal activity, and brain adrenoceptors' (ARs) expression (alpha2-ARs and beta-ARs) were determined using in vivo 2-[(14)C]-deoxyglucose methodology and in vitro neurotransmitter receptors quantitative autoradiography, respectively. Intriguingly, females exhibited higher glucose utilization than males in hypothalamic brain areas. Adrenoceptor's expression pattern was dimorphic in zebrafish telencephalic, preoptic, hypothalamic nuclei, central gray, and cerebellum, similarly to birds and mammals. Specifically, the lateral zone of dorsal telencephalon (Dl), an area related to spatial cognition, homologous to the mammalian hippocampus, showed higher alpha2-AR densities in females. In contrast, male cerebellum included higher densities of beta-ARs in comparison to female. Taken together, our data demonstrate a well-defined sex discriminant cerebral metabolic activity and ARs' pattern in zebrafish, possibly contributing to male-female differences in the swimming behavior. PMID- 27363928 TI - Hysteroscopic-guided local endometrial injury does not improve natural cycle pregnancy rate in women with unexplained infertility: Randomized controlled trial. AB - AIM: To evaluate the efficacy of a hysteroscopic site-specific local endometrial injury (LEI) in a group of women with unexplained infertility (UI) undergoing expectant management with no fertility treatment versus no intervention. METHODS: This open-label, randomized controlled trial (RCT) was conducted between June 2013 and July 2015. Hysteroscopic site-specific LEI was determined by patient identification number, and 120 women were included. Eligible participants were randomly assigned to receive either a single, site-specific LEI guided by hysteroscopy (study group, n = 60) or no intervention (control group, n = 60). Natural cycle folliculometry and timed intercourse were carried out for all participants for 3 months. Successful clinical pregnancy confirmed on ultrasound was the primary outcome measure, and first trimester miscarriage rate was the secondary outcome. RESULTS: After identification, baseline clinical demographics were similar in the two groups. No statistically significant differences were noted in cumulative pregnancy rates in women with LEI compared with those without (16.7% and 11.7 %, respectively; OR, 2.83; 95%CI: 1.07-7.48; P = 0.4). One first trimester miscarriage was reported in the control group (14.3%). CONCLUSION: Local endometrial injury for natural cycle conception in women with UI is not justified. Further RCT are warranted to prove or disprove this. PMID- 27363929 TI - The effects of vitamin D supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial. AB - OBJECTIVE: This study was conducted to evaluate the effects of vitamin D supplementation on wound healing and metabolic status in patients with diabetic foot ulcer (DFU). METHODS: This randomized, double-blind, placebo-controlled trial was performed among 60 patients with grade 3 DFU according to "Wagner Meggitt's" criteria. Participants were randomly divided into two groups (each 30 participants) and received either 50,000IU vitamin D supplements every 2weeks for 12weeks (group A) or placebo (group B). Fasting blood samples were taken at study baseline and after 12-week intervention to determine related markers. RESULTS: After 12weeks of intervention, compared with the placebo, vitamin D supplementation resulted in a significant reduction in ulcer length (-2.1+/-1.1 vs. -1.1+/-1.1cm, P=0.001), width (-2.0+/-1.2 vs. -1.1+/-1.0cm, P=0.02) and depth (-1.0+/-0.5 vs. -0.5+/-0.5cm, P<0.001), and erythema rate (100% vs. 80%, P=0.01). In addition, in supplemented patients changes in serum insulin concentration ( 3.4+/-9.2 vs. +2.8+/-9.3 MUIU/mL, P=0.01), homeostasis model of assessment estimated insulin resistance (-1.5+/-4.1 vs. +1.7+/-5.1, P=0.01), the quantitative insulin sensitivity check index (+0.006+/-0.02 vs. -0.006+/-0.02, P=0.03) and HbA1c (-0.6+/-0.6 vs. -0.1+/-0.5%, P=0.004) were significantly different from those of patients in the placebo group. Additionally, following supplementation with vitamin D, significant reductions in serum total- (-15.8+/ 18.9 vs. +5.3+/-31.8mg/dL, P=0.003), LDL- (-17.2+/-19.8 vs. +2.2+/-28.6mg/dL, P=0.003), total-/HDL-cholesterol ratio (-1.1+/-0.8 vs. -0.2+/-1.1, P=0.001), high sensitivity C-reactive protein (hs-CRP) (-0.4+/-2.5 vs. +1.9+/-4.2MUg/mL, P=0.01), erythrocyte sedimentation rate (ESR) (-34.7+/-32.4 vs. -18.0+/-26.6mm/h, P=0.03) and plasma malondialdehyde (MDA) concentrations (-0.7+/-0.9 vs. -0.2+/ 0.5MUmol/L, P=0.008) were seen compared with the placebo. CONCLUSIONS: Overall, vitamin D supplementation for 12weeks among patients with DFU had beneficial effects on glucose homeostasis, total-, LDL-, total-/HDL-cholesterol, ESR, hs-CRP and MDA levels. In addition, vitamin D may have played an indirect role in wound healing due to its effect on improved glycemic control. PMID- 27363930 TI - Optical gain in GaAsBi/GaAs quantum well diode lasers. AB - Electrically pumped GaAsBi/GaAs quantum well lasers are a promising new class of near-infrared devices where, by use of the unusual band structure properties of GaAsBi alloys, it is possible to suppress the dominant energy-consuming Auger recombination and inter-valence band absorption loss mechanisms, which greatly impact upon the device performance. Suppression of these loss mechanisms promises to lead to highly efficient, uncooled operation of telecommunications lasers, making GaAsBi system a strong candidate for the development of next-generation semiconductor lasers. In this report we present the first experimentally measured optical gain, absorption and spontaneous emission spectra for GaAsBi-based quantum well laser structures. We determine internal optical losses of 10-15 cm( 1) and a peak modal gain of 24 cm(-1), corresponding to a material gain of approximately 1500 cm(-1) at a current density of 2 kA cm(-2). To complement the experimental studies, a theoretical analysis of the spontaneous emission and optical gain spectra is presented, using a model based upon a 12-band k.p Hamiltonian for GaAsBi alloys. The results of our theoretical calculations are in excellent quantitative agreement with the experimental data, and together provide a powerful predictive capability for use in the design and optimisation of high efficiency lasers in the infrared. PMID- 27363931 TI - [Endobronchial ultrasonography (EBUS) for the internist]. AB - Endobronchial ultrasonography (EBUS) is a recent mini-invasive technique allowing transbronchial needle aspiration (TBNA) of mediastinal lymph nodes as well as peribronchial lesions. EBUS was initially developed for lung cancer mediastinal staging. Over the years, indications for EBUS have been progressively extended to the scope of inflammatory disorders, mediastinal lymphomas, and infectious diseases. Particularly in immunosuppressed patients, including HIV-infected patients, EBUS allows the diagnosis of several diseases that involve the mediastinum, avoiding invasive surgical explorations such as mediastinoscopy or thoracoscopy. This review aims at discussing the technical aspects, and specifies indications, results, and limits of EBUS for the internist. PMID- 27363932 TI - [Central nervous system lymphoma revealed by lymphocytic meningitis in a patient with systemic lupus erythematosus: An unusual association]. AB - INTRODUCTION: We report an unusual observation of central nervous system (CNS) lymphoma in a 60-year-old woman with systemic lupus erythematosus and fatal outcome. OBSERVATION: The patient had systemic erythematosus lupus for 7 years, treated with mycophenolate mofetil and developed lymphocytic meningitis in 2015 associated to the presence of EBV in the cerebrospinal fluid and a necrotic vermis' lesion. Diagnosis of large B-cell lymphoma was histologically confirmed from stereotaxic biopsy, shortly before she died from neurological complications. CONCLUSION: Even though the current association is unusual, lymphocytic meningitis with hypoglycorrachia in patients with systemic lupus erythematosus may reveal CNS lymphoma and diagnosis confirmation requires stereotaxic biopsy in order not to delay specific therapeutic management. PMID- 27363933 TI - [The clinician: The first of all essential drugs. A defense for clinician medicine and the patient-physician relationship]. PMID- 27363934 TI - Design and syntheses of mono and multivalent mannosyl-lipoconjugates for targeted liposomal drug delivery. AB - Multivalent mannosyl-lipoconjugates may be of interest for glycosylation of liposomes and targeted drug delivery because the mannose specifically binds to C type lectin receptors on the particular cells. In this paper syntheses of two types of novel O-mannosides are presented. Conjugates 1 and 2 with a COOH- and NH2-functionalized spacer and the connection to a lysine and FmocNH-PEG-COOH, are described. The coupling reactions of prepared intermediates 6 and 4 with a PEGylated-DSPE or palmitic acid, respectively, are presented. Compounds 5, mono-, 8, di- and 12, tetravalent mannosyl-lipoconjugates, were synthesized. The synthesized compounds were incorporated into liposomes and liposomal preparations featuring exposed mannose units were characterized. Carbohydrate liposomal quartz crystal microbalance based assay has been established for studying carbohydrate lectin binding. It was demonstrated that liposomes with incorporated mannosyl lipoconjugates were effectively recognized by Con A and have great potential to be used for targeted liposomal drug delivery systems. PMID- 27363935 TI - Effect of aqueous and particulate silk fibroin in a rat model of experimental colitis. AB - Silk fibroin (SF) has anti-inflammatory properties and promotes wound healing. Moreover, SF particles act as carriers of active drugs against intestinal inflammation due to their capacity to deliver the compound to the damaged colonic tissue. The present work assesses the effect of SF in the trinitrobenzenesulfonic acid model of rat colitis that resembles human intestinal inflammation. SF (8mg/kg) was administered in aqueous solution orally and in two particulate formats by intrarectal route, following two technologies: spray drying to make microparticles and desolvation in organic solvent to produce nanoparticles. SF treatments ameliorated the colonic damage, reduced neutrophil infiltration and improved the compromised oxidative status of the colon. They also reduced the gene expression of pro-inflammatory cytokines like IL-1beta and the anti inflammatory cytokine IL-10. Moreover, they improved the intestinal wall integrity by increasing the gene expression of some of its markers (villin, trefoil factor-3 and mucins), thus accelerating the healing. The immunomodulatory properties of SF particles were also tested in vitro in macrophages: they activated the immune response in basal conditions without increasing it after a pro-inflammatory insult. In conclusion, SF particles could be useful as carriers to deliver active drugs to the damaged intestinal colon with additional anti inflammatory and healing properties. PMID- 27363936 TI - Non-covalent modification of granulocyte-colony stimulating factor (G-CSF) by coiled-coil technology. AB - We present here an approach to non-covalently combine an engineered model protein with a PEGylated peptide via coiled-coil binding. To this end a fusion protein of G-CSF and the peptide sequence (JunB) was created-one sequence of JunB was expressed at the N-terminal of GCSF. JunB is able to bind to the peptide sequence cFos, which was in turn covalently linked to a chain of poly(ethylene glycol) (PEG). The selected peptide sequences are leucine zipper motives from transcription factors and are known to bind to each other specifically by formation of a super secondary structure called coiled-coil. The binding between PEGylated peptides of various molecular weights and the modified protein was assessed by isothermal calorimetry (ITC), dynamic light scattering (DLS), circular dichroism (CD), and fluorescence anisotropy. Our findings show that the attachment of 2 and 5kDa PEG does not interfere with coiled-coil formation and thus binding of peptide to fusion protein. With this work we successfully demonstrate the non-covalent binding of a model moiety (PEG) to a protein through coiled-coil interaction. PMID- 27363937 TI - Tat peptide and hexadecylphosphocholine introduction into pegylated liposomal doxorubicin: An in vitro and in vivo study on drug cellular delivery, release, biodistribution and antitumor activity. AB - We have investigated the co-addition of hexadecylphosphocholine (HePC) and a Tat derived peptide (Tat), coupled to Maleimide-PEG2000-DSPE pegylated liposomal doxorubicin (PLD) in many respects, including drug and liposome cellular delivery, drug release, biodistribution, in vivo cell delivery and antitumor activity. The liposomes were HePC-free and -containing liposomes, from which liposomes with 25, 50, 100 and 200 numbers of Tat/liposome were prepared. Similarly, DiI-C18 (3)-model liposomes (DiI-L and DiI-HePC-L) were prepared. HePC and Tat increased cellular delivery of Dox and cytotoxicity in B16F0 melanoma and C26 colon carcinoma cells. Tat enhanced liposome-cell interaction and caused Dox burst release. HePC and Tat reduced the serum retention time of liposomal Dox, slightly and dramatically, respectively. In comparison, Tat-liposomes enhanced Dox delivery to liver and spleen cells 3h post-injection. Likewise, Dox content of these tissues and tumor was lower at 24h. The naive liposomes retarded tumor growth more effectively and their related median survival time of the treated C26 bearing BALB/c mice was longer than those of Tat-liposomes (MST>45days versus MST<38days). Overall liposomes exhibiting sustained drug release and negligible cell interaction were more suitable delivery systems in targeting cancerous tumors and suppressing their growth. PMID- 27363938 TI - A chromatography-free isolation of rohitukine from leaves of Dysoxylum binectariferum: Evaluation for in vitro cytotoxicity, Cdk inhibition and physicochemical properties. AB - Rohitukine is a chromone alkaloid isolated from an Indian medicinal plant Dysoxylum binectariferum. This natural product has led to the discovery of two clinical candidates (flavopiridol and P276-00) for the treatment of cancer. Herein, for the first time we report an efficient protocol for isolation and purification of this precious natural product in a bulk-quantity from leaves (a renewable source) of D. binectariferum (>98% purity) without use of chromatography or any acid-base treatment. Despite of the fact that this scaffold has reached up to clinical stage, particularly for leukemia; however the antileukemic activity of a parent natural product has never been investigated. Furthermore, rohitukine has never been studied for cyclin-dependent kinase (Cdk) inhibition, kinase profiling and for its experimental physicochemical properties. Thus, herein, we report in vitro cytotoxicity of rohitukine in a panel of 20 cancer cell lines (including leukemia, pancreatic, prostate, breast and CNS) and 2 normal cell lines; kinase profiling, Cdk2/9 inhibition, and physicochemical properties (solubility and stability in biological medias, pKa, LogP, LogD). In cytotoxicity screening, rohitukine displayed promising activity in HL-60 and Molt 4 (leukemia) cell lines with GI50 of 10 and 12MUM, respectively. It showed inhibition of Cdk2/A and Cdk9/T1 with IC50 values of 7.3 and 0.3MUM, respectively. The key interactions of rohitukine with Cdk9 was also studied by molecular modeling. Rohitukine was found to be highly water soluble (Swater=10.3mg/mL) and its LogP value was -0.55. The ionization constant of rohitukine was found to be 5.83. Rohitukine was stable in various biological media's including rat plasma. The data presented herein will help in designing better anticancer agents in future. PMID- 27363939 TI - New insights into 3-(aminomethyl)naphthoquinones: Evaluation of cytotoxicity, electrochemical behavior and search for structure-activity correlation. AB - Herein we describe the structure-activity relationship of a large library of Mannich bases (MBs) synthesized from 2-hydroxy-1,4-naphthoquinone. In general, the compounds have shown high to moderate activity against the HL-60 (promyelocytic leukaemia) cell line with IC50=1.1-19.2MUM. Our results suggest that the nature of the aryl moiety introduced in the structure of MBs by the aldehyde component is crucial to the cytotoxicity, and although the group originated from the primary amine has a lesser influence, aromatic ones were found to suppress the activity. Thus, MBs derived from salicylaldehydes or 2 pyridinecarboxaldehyde and aliphatic amines are the most active compounds. A satisfactory correlation of the EpIIc versus IC50 (MUM) in dimethylsulfoxide was observed. The most cytotoxic MBs (Series a-c, derived from salicylaldehydes) showed the least negative EpIIc values. Noteworthy, however, Series d (derived from 2-pyridinecarboxaldehyde) did not follow this correlation. They exhibited both the lowest IC50 and the most negative EpIIc values, thus suggesting that other factors also influence the cytotoxicity of the MBs, such as lipophilicity, electronic distribution and hydrogen bonding. PMID- 27363940 TI - Kinetic investigation of human 5-lipoxygenase with arachidonic acid. AB - Human 5-lipoxygenase (5-LOX) is responsible for the formation of leukotriene (LT)A4, a pivotal intermediate in the biosynthesis of the leukotrienes, a family of proinflammatory lipid mediators. 5-LOX has thus gained attention as a potential drug target. However, details of the kinetic mechanism of 5-LOX are still obscure. In this Letter, we investigated the kinetic isotope effect (KIE) of 5-LOX with its physiological substrate, arachidonic acid (AA). The observed KIE is 20+/-4 on kcat and 17+/-2 on kcat/KM at 25 degrees C indicating a non classical reaction mechanism. The observed rates show slight temperature dependence at ambient temperatures ranging from 4 to 35 degrees C. Also, we observed low Arrhenius prefactor ratio (AH/AD=0.21) and a small change in activation energy (Ea(D)-Ea(H)=3.6J/mol) which suggests that 5-LOX catalysis involves tunneling as a mechanism of H-transfer. The measured KIE for 5-LOX involves a change in regioselectivity in response to deuteration at position C7, resulting in H-abstraction form C10 and formation of 8-HETE. The viscosity experiments influence the (H)kcat, but not (D)kcat. However the overall kcat/KM is not affected for labeled or unlabeled AA, suggesting that either the product release or conformational rearrangement might be involved in dictating kinetics of 5-LOX at saturating conditions. Investigation of available crystal structures suggests the role of active site residues (F421, Q363 and L368) in regulating the donor-acceptor distances, thus affecting H-transfer as well as regiospecificity. In summary, our study shows that that the H-abstraction is the rate limiting step for 5-LOX and that the observed KIE of 5-LOX is masked by a change in regioselectivity. PMID- 27363941 TI - Zinc transporter 8 autoantibodies assessment in daily practice. AB - OBJECTIVES: Zinc transporter 8 (ZnT8) is specifically expressed in the pancreatic beta-cell and is more restricted in its tissue distribution than other auto antigens as glutamic acid decarboxylase 65 (GAD65) and insulinoma-associated antigen-2 (IA2). ZnT8 autoantibodies (ZnT8A) assessment allows identifying rapid progression to clinical onset of the disease. We evaluated the prevalence of ZnT8A in adults of different ethnic and phenotypic groups and analyzed its potential utility as additional marker of autoimmunity in daily practice. METHODS: ZnT8A, GADA and IA2A were assessed using enzyme-linked immune-sorbent assay (ELISA) in 160 controls and 216 diabetic subjects. 105 were of type 1 diabetes (T1D), 17 had Latent Autoimmune Diabetes of Adults (LADA), 38 were type 2 diabetic (T2D) and 56 had ketosis-prone diabetes (KPD). 82 patients were newly diagnosed cases. RESULTS: ZnT8A were detected in 1% of controls and were not found in any of our 38 T2D subjects or 56 KPD subjects. In contrast, ZnT8A were detected in 18% of LADA subjects and in 38% of T1D subjects. A slight difference of percentage of ZnT8A positivity was found among our T1D ethnic groups. ZnT8A were positive in 41% of patients positive for GADA and 67% of patients positive for IA2A. The percentage of stratification achieved 91% when GADA, IA2A and ZnT8A were assessed simultaneously. CONCLUSIONS: Results obtained for ZnT8A measurement using ELISA were consistent with previous data. Such investigation could improve the risk stratification and would be integrated in our daily practice. PMID- 27363942 TI - The interobserver reliability of a novel qualitative point of care assay for heart-type fatty acid binding protein. AB - BACKGROUND: Heart-type fatty acid-binding protein (h-FABP) may help to improve the early diagnosis of acute coronary syndromes in patients presenting to the Emergency Department (ED) with chest pain. A novel qualitative point of care h FABP lateral flow immunoassay (True Rapid, FABPulous BV) could provide results to clinicians within just 5min. Given the qualitative nature of this test and prior to evaluation in a large diagnostic study, we aimed to determine inter-observer reliability when interpreted contemporaneously by staff in the ED. METHODS: In a nested prospective cohort study including adult patients with suspected cardiac chest pain, venous blood samples were tested for h-FABP (FABPulous BV) on arrival and 3h later. Each test result was independently interpreted by two different investigators after 5min. The investigators were blinded to each other's interpretation and recorded their findings on separate case report forms. We determined interobserver reliability by calculating the Cohen's kappa score and 95% confidence intervals. RESULTS: A total of 43 test results (from 31 patients) were each interpreted by two independent investigators. Absolute agreement between investigators was 93.0%, with a Cohen's kappa of 0.81 (95% CI 0.6-1.0), indicating near perfect agreement. In total there were three (7.0%) disagreements. In each case one investigator reported a 'weak positive' result while the other interpreted the result as 'negative'. CONCLUSIONS: These findings demonstrate the interobserver reliability of a qualitative point of care h-FABP assay. Further work must evaluate diagnostic accuracy and determine the clinical implications of the small rate of disagreement. PMID- 27363943 TI - Development and application of loop-mediated isothermal amplification (LAMP) for detection of Plasmopara viticola. AB - A rapid LAMP (loop-mediated isothermal amplification) detection method was developed on the basis of the ITS sequence of P. viticola, the major causal agent of grape downy mildew. Among the 38 fungal and oomycete species tested, DNA isolated exclusively from P. viticola resulted in a specific product after LAMP amplification. This assay had high sensitivity and was able to detect the presence of less than 33 fg of genomic DNA per 25-MUL reaction within 30 min. The infected leaves may produce sporangia that serve as a secondary inoculum. The developed LAMP assay is efficient for estimating the latent infection of grape leaves by P. viticola. When combined with the rapid and simple DNA extraction method, this assay's total detection time is shortened to approximately one hour; therefore it is suitable for on-site detection of latent infection in the field. The sporangia levels in the air are strongly associated with disease severity. The LAMP method was also demonstrated to be able to estimate the level of sporangia released in the air in a certain period. This assay should make disease forecasting more accurate and rapid and should be helpful in decision-making regarding the control of grape downy mildew. PMID- 27363944 TI - Gas-solid interfacial modification of oxygen activity in layered oxide cathodes for lithium-ion batteries. AB - Lattice oxygen can play an intriguing role in electrochemical processes, not only maintaining structural stability, but also influencing electron and ion transport properties in high-capacity oxide cathode materials for Li-ion batteries. Here, we report the design of a gas-solid interface reaction to achieve delicate control of oxygen activity through uniformly creating oxygen vacancies without affecting structural integrity of Li-rich layered oxides. Theoretical calculations and experimental characterizations demonstrate that oxygen vacancies provide a favourable ionic diffusion environment in the bulk and significantly suppress gas release from the surface. The target material is achievable in delivering a discharge capacity as high as 301 mAh g(-1) with initial Coulombic efficiency of 93.2%. After 100 cycles, a reversible capacity of 300 mAh g(-1) still remains without any obvious decay in voltage. This study sheds light on the comprehensive design and control of oxygen activity in transition-metal-oxide systems for next-generation Li-ion batteries. PMID- 27363945 TI - Preparation and unique dielectric properties of nanoporous materials with well controlled closed-nanopores. AB - Although general porous materials have a low dielectric constant, their uncontrollable opened porous structure results in high dielectric loss and poor barrier properties, thus limiting their application as interconnect dielectrics. In this study, polymeric nanoporous materials with well-controlled closed pores were prepared by incorporating polystyrene (PS) hollow nanoparticles into polyethylene (PE/HoPS). SEM images suggested a closed porous structure for PE/HoPS. In order to show the effect of the porous structure on dielectric properties, nanoporous materials with an opened or uncontrollable porous structure were prepared by etching SiO2/PE or PE/PS@SiO2 composites. PE/HoPSs composites showed an apparently lower dielectric constant and loss compared with the opened porous PE, demonstrating the advantages of a closed porous structure upon enhancing low-dielectric performance. The low dielectric performance of the PE/HoPS composites is linked with high water resistance owing to their closed porous characteristics. When incorporating 15.3 wt% HoPS (porosity: ~6.9%), the dielectric constant reached 2.08. This value is lower than that calculated from the serial model. Our work revealed that the incorporation of HoPS not only reduces the porosity, but also alters the intrinsic properties of PE, as a result, leading to a greatly reduced dielectric constant. PMID- 27363946 TI - Anger and stroke: a potential association that deserves serious consideration. AB - OBJECTIVE: To assess the relationship between states of anger and stroke. METHODS: Systematic review of the literature. RESULTS: In total, 21 papers were selected for the systematic review of data published on the subject of anger and stroke. A state of anger may be a risk factor for stroke, as well as a consequence of brain lesions affecting specific areas that are caused by a stroke. Scales to assess anger varied among authors. There was no consensus regarding the area of brain lesions that might lead to a state of anger. Although some authors agreed that lesions on the right side led to angrier behaviour, others found that lesions on the left side were more relevant to anger. Likewise, there was no consensus regarding the prevalence of anger pre or post-stroke. Some authors did not even find that these two conditions were related. CONCLUSION: Although most authors have accepted that there is a relationship between anger and stroke, studies with uniform methodology need to be conducted if this association is to be properly evaluated and understood. PMID- 27363947 TI - Classification of fracture and non-fracture groups by analysis of coherent X-ray scatter. AB - Osteoporotic fractures present a significant social and economic burden, which is set to rise commensurately with the aging population. Greater understanding of the physicochemical differences between osteoporotic and normal conditions will facilitate the development of diagnostic technologies with increased performance and treatments with increased efficacy. Using coherent X-ray scattering we have evaluated a population of 108 ex vivo human bone samples comprised of non fracture and fracture groups. Principal component fed linear discriminant analysis was used to develop a classification model to discern each condition resulting in a sensitivity and specificity of 93% and 91%, respectively. Evaluating the coherent X-ray scatter differences from each condition supports the hypothesis that a causal physicochemical change has occurred in the fracture group. This work is a critical step along the path towards developing an in vivo diagnostic tool for fracture risk prediction. PMID- 27363948 TI - Adverse vascular remodelling is more sensitive than endothelial dysfunction to hyperglycaemia in diabetic rat mesenteric arteries. AB - Increased vascular stiffness and reduced endothelial nitric oxide (NO) bioavailability are characteristic of diabetes. Whether these are evident at a more moderate levels of hyperglycaemia has not been investigated. The objectives of this study were to examine the association between the level of glycaemia and resistance vasculature phenotype, incorporating both arterial stiffness and endothelial function. Diabetes was induced in male Sprague Dawley rats with streptozotocin (STZ; 55mg/kg i.v.) and followed for 8 weeks. One week post STZ, diabetic rats were allocated to either moderate (~20mM blood glucose, 6 7U/insulins.c. daily) or severe hyperglycaemia (~30mM blood glucose, 1 2U/insulins.c. daily as required). At study end, rats were anesthetized, and the mesenteric arcade was collected. Passive mechanical wall properties were assessed by pressure myography. Responses to the endothelium-dependent vasodilator acetylcholine (ACh) were assessed using wire myography. Our results demonstrated for the first time that mesenteric arteries from both moderate and severely hyperglycaemic diabetic rats exhibited outward hypertrophic remodelling and increased axial stiffness compared to arteries from non-diabetic rats. Secondly, mesenteric arteries from severely (~30mM blood glucose), but not moderately hyperglycaemic (~20mM blood glucose) rats exhibit a significant reduction to ACh sensitivity compared to their non-diabetic counterparts. This endothelial dysfunction was associated with significant reduction in endothelium-derived hyperpolarisation and endothelium-dependent NO-mediated relaxation. Interestingly, endothelium-derived nitroxyl (HNO)-mediated relaxation was intact. Therefore, moderate hyperglycaemia is sufficient to induce adverse structural changes in the mesenteric vasculature, but more severe hyperglycaemia is essential to cause endothelial dysfunction. PMID- 27363950 TI - Analog Computation by DNA Strand Displacement Circuits. AB - DNA circuits have been widely used to develop biological computing devices because of their high programmability and versatility. Here, we propose an architecture for the systematic construction of DNA circuits for analog computation based on DNA strand displacement. The elementary gates in our architecture include addition, subtraction, and multiplication gates. The input and output of these gates are analog, which means that they are directly represented by the concentrations of the input and output DNA strands, respectively, without requiring a threshold for converting to Boolean signals. We provide detailed domain designs and kinetic simulations of the gates to demonstrate their expected performance. On the basis of these gates, we describe how DNA circuits to compute polynomial functions of inputs can be built. Using Taylor Series and Newton Iteration methods, functions beyond the scope of polynomials can also be computed by DNA circuits built upon our architecture. PMID- 27363949 TI - mTOR-Independent autophagy inducer trehalose rescues against insulin resistance induced myocardial contractile anomalies: Role of p38 MAPK and Foxo1. AB - Insulin resistance is associated with cardiovascular diseases although the precise mechanisms remain elusive. Akt2, a critical member of the Akt family, plays an essential role in insulin signaling. This study was designed to examine the effect of trehalose, an mTOR-independent autophagy inducer, on myocardial function in an Akt2 knockout-induced insulin resistance model. Adult WT and Akt2 knockout (Akt2(-/-)) mice were administered trehalose (1mg/g/day, i.p.) for two days and were then given 2% trehalose in drinking water for two more months. Echocardiographic and myocardial mechanics, intracellular Ca(2+) properties, glucose tolerance, and autophagy were assessed. Apoptosis and ER stress were evaluated using TUNEL staining, Caspase 3 assay and Western blot. Autophagy and autophagy flux were examined with a focus on p38 mitogen activated protein kinase (MAPK), Forkhead box O (Foxo1) and Akt. Akt2 ablation impaired glucose tolerance, myocardial geometry and function accompanied with pronounced apoptosis, ER stress and dampened autophagy, the effects of which were ameliorated by trehalose treatment. Inhibition of lysosomal activity using bafilomycin A1 negated trehalose-induced induction of autophagy (LC3B-II and p62). Moreover, phosphorylation of p38 MAPK and Foxo1 were upregulated in Akt2(-/-) mice, the effect of which was attenuated by trehalose. Phosphorylation of Akt was suppressed in Akt2(-/-) mice and was unaffected by trehalose. In vitro findings revealed that the p38 MAPK activator anisomycin and the Foxo1 inhibitor (through phosphorylation) AS1842856 effectively masked trehalose-offered beneficial cardiomyocyte contractile response against Akt2 ablation. These data suggest that trehalose may rescue against insulin resistance-induced myocardial contractile defect and apoptosis, via autophagy associated with dephosphorylation of p38 MAPK and Foxo1 without affecting phosphorylation of Akt. PMID- 27363951 TI - Sanguinarine Induces Apoptosis of Human Oral Squamous Cell Carcinoma KB Cells via Inactivation of the PI3K/Akt Signaling Pathway. AB - Preclinical Research Sanguinarine, an alkaloid isolated from the root of Sanguinaria canadensis and other plants of the Papaveraceae family, selectively induces apoptotic cell death in a variety of human cancer cells, but its mechanism of action requires further elaboration. The present study investigated the pro-apoptotic effects of sanguinarine in human oral squamous cell carcinoma KB cells. Sanguinarine treatment increased DR5/TRAILR2 (death receptor 5/TRAIL receptor 2) expression and enhanced the activation of caspase-8 and cleavage of its substrate, Bid. Sanguinarine also induced the mitochondrial translocation of pro-apoptotic Bax, mitochondrial dysfunction, cytochrome c release to the cytosol, and activation of caspase-9 and -3. However, a pan-caspase inhibitor, z VAD-fmk, reversed the growth inhibition and apoptosis induced by sanguinarine. Sanguinarine also suppressed the phosphorylation of phosphoinositide 3-kinase (PI3K) and Akt in KB cells, while co-treatment of cells with sanguinarine and a PI3K inhibitor revealed synergistic apoptotic effects. However, pharmacological inhibition of AMP-activated protein kinase and mitogen-activated protein kinases did not reduce or enhance sanguinarine-induced growth inhibition and apoptosis. Collectively, these findings indicate that the pro-apoptotic effects of sanguinarine in KB cells may be regulated by a caspase-dependent cascade via activation of both intrinsic and extrinsic signaling pathways and inactivation of PI3K/Akt signaling. Drug Dev Res 77 : 227-240, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27363952 TI - Long-term Treatment with Hesperidin Improves Endothelium-dependent Vasodilation in Femoral Artery of Spontaneously Hypertensive Rats: The Involvement of NO synthase and Kv Channels. AB - Hesperidin is the most common flavonoid found in citrus fruits and is expected to exert vasodilation action relevant to its health benefits. The present study aimed to explore the effect of hesperidin on the vascular responses in normotensive and hypertensive rats and the involvement of NO-synthase and Kv channels. The 15-week-old Wistar and spontaneously hypertensive rats (SHR) were randomized to orally receive either hesperidin (50 mg/kg/day) or a corresponding volume of the water for 4 weeks. Vascular responses of isolated femoral arteries were studied with myograph in control conditions and during inhibition of NO synthase with l-NNA and Kv channels with 4-AP. Hesperidin had no effect on blood pressure. Endothelium-dependent vasodilation in Wistar and SHR was significantly improved by the treatment with hesperidin. The contraction responses after l-NNA were increased in all groups of rats to similar extent, but relaxatory responses were significantly attenuated only in SHR. The inhibition of Kv channels significantly reduced endothelium-dependent vasodilatory responses in only in SHR administered with hesperidin. The results of our experiment indicate that hesperidin might improve the endothelium-dependent vasodilation during hypertension, possibly through the enhancement of Kv channels function. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27363953 TI - Neovascular AMD: Where do we go from here? PMID- 27363954 TI - Diabetic macular edema. PMID- 27363955 TI - Comparing biometry in normal eyes of children with unilateral cataract/corneal disease to age-matched controls. AB - OBJECTIVE: To compare ocular biometry and central corneal thickness of unaffected healthy eyes of pediatric patients with monocular cataracts/corneal opacities and age- matched controls. MATERIALS AND METHODS: We studied 329 eyes of 329 children who were between 1 and 12 years old. The study group (n: 164) consisted of healthy fellow eyes of children operated for unilateral congenital/traumatic cataract and corneal laceration. Axial length, anterior chamber depth, lens thickness, vitreous chamber depth, and central corneal thickness were measured by ultrasound biometry/ pachymetry. RESULTS: Axial length was 22.16 mm in the study group and 21.99 mm in the control group. Anterior chamber depth, lens thickness, and vitreous chamber depth results were 3.35; 3.64 and 15.20 in the treatment group and 3.20; 3.63, and 15.15 mm in the control group, respectively. The axial length and all the components, i.e. anterior chamber depth, lens thickness, and vitreous chamber depth are higher in the unaffected healthy eyes of the pediatric patients than that of the control group but only the difference in the anterior chamber depth was statistically significant. The central corneal thickness was 548 microns and 559 microns in the study and the control groups, respectively, and the difference was found to be significant. CONCLUSION: Greater anterior chamber depth was chiefly responsible for the overall increase in the axial length in the study group. The central corneal thickness was significantly thinner in the study group than that of the control group. Keywords Ocular biometry; central corneal thickness; anterior chamber depth; lens thickness; vitreous chamber depth. PMID- 27363956 TI - Ischemia modified albumin (IMA) and albumin adjusted-IMA (AAIMA) as biomarkers for diabetic retinopathy. AB - INTRODUCTION: Oxidative stress has important role in the pathophysiology of diabetic retinopathy (DR). Ischemia modified albumin (IMA) has been recently considered as a marker of oxidative damage in diabetes. However, there is scarcity of published information about both IMA and albumin adjusted-IMA (AAIMA) in DR patients. OBJECTIVES: To evaluate the serum levels of IMA and AAIMA in patients with DR and in healthy controls. MATERIAL AND METHODS: This was a cross sectional study. Serum was obtained to measure lipids, albumin and IMA from the the patients with DR and non-diabetic subjects. The IMA level was measured by a colorimetric albumin cobalt binding (ACB) assay and the values were presented as absorbance units (ABSU). The IMA levels were adjusted for albumin interference and the AAIMA by using a formula [Individual serum albumin/median albumin concentration of the population X IMA]. RESULTS: This study was done on 18 DR and 20 non- diabetic patients. The mean Serum IMA values in DR group and controls were 0.50+/-0.17 and 0.32+/-0.17, respectively (P=0.002). The mean serum AAIMA values in DR group and controls were 0.48+/-0.20 and 0.32+/-0.17, respectively (P=0.01). The albumin and HDL- Cholesterol levels were significantly lower in DR patients compared to controls (p=0.004 and p=0.01, respectively). CONCLUSIONS: The level of IMA and AAIMA were higher in cases of DR compared to that of non diabetic subjects. The levels of albumin and HDL-Cholesterol were lower in DR patients compared to controls. PMID- 27363957 TI - Comparison of endothelial cell loss and complications between phacoemulsification and manual small incision cataract surgery (SICS) in uveitic cataract. AB - INTRODUCTION: Endothelial cell loss and complications after cataract surgery may be higher when cataract is complicated by uveitis. OBJECTIVE: To compare endothelial cell damage and complication rates after phacoemulsification and manual small incision cataract surgery (SICS) in patients with uveitis. MATERIALS AND METHODS: Patients with uveitic cataract were randomly allocated for phacoemulsification (n=75) or manual SICS (n=80) in a double blind prospective study. In the bag implantation of a hydrophobic acrylic intraocular lens was aimed in all cases. Patients with follow up of less than six months were excluded. Main outcome measures were alteration in endothelial cell counts (ECC) and morphology, improvement in vision and complication rates. ECC was measured preoperatively and at 1 week, 3 months and six months, postoperatively. RESULTS: Six patients were lost to follow up and another three due inability to implant IOL. There were no significant difference in endothelial cell counts (P= 0.032), the variance of endothelial cell size (CV) and percentage of hexagonal cells between both the groups at six months (Mann-Whitney test, P=0.283). Endothelial cell density was significantly less in the group in which vitrectomy and/or pupil dilatation procedures were performed (2290+/-31.5 cells/mm2) versus (2385+/-50.3 cells/mm2), respectively (t test, P less than0.001). Incidence of postoperative complications that were observed like persistent uveitis (P=0.591), macular edema (P=0.671) and PCO (P=0.678) and visual outcome (P=0.974) were comparable between the two groups. CONCLUSIONS: Manual SICS and phacoemulsification do not differ significantly in endothelial cell loss and complication rates in uveitic eyes. However, increased anterior chamber manoeuvring due to additional procedures may lead to significantly higher endothelial cell loss. PMID- 27363958 TI - Neurocysticercosis - A Window to Intraocular Involvement. AB - OBJECTIVE: To analyse the clinical characteristics of intraocular cysticercosis and the association of neurocysticercosis with intraocular involvement in these patients Materials and methods: Retrospective case series of records of patients managed at a Tertiary Care Hospital in South India. Case records of patients managed at a Tertiary Care Hospital in South India over two years (October 2012 - October 2014) were reviewed and cases reported with intraocular cysticercosis were included in the study and results analyzed. RESULTS: Five (5) patients of intraocular cysticercosis were diagnosed in a two year period at our centre, 60% being bilateral. Eight (8) eyes of five (5) patients had intraocular cysts documented by clinical examination and B mode ultrasonography (75% eyes with active cysts, 25% eyes inactive) .Visual acuity at presentation of eyes with active cysts ranged from perception of light to counting finger 4m. The 75% eyes had tractional retinal detachment at presentation. Neurocysticercosis was documented in 80% of the cases oncomputed tomography / magnetic resonance imaging . Six (6) eyes with active cysts underwent parsplanavitrectomy with cyst removal using vitreous cutter with concurrent management of tractional retinal detachment in five (5) eyes. Postoperative visual recovery was poor in eyes with associated tractional retinal detachment while good anatomical outcome was achieved in all six (6) cases. CONCLUSION: Intraocular cysticercosis can be associated with cysts in other areas. High number of patients with neurocysticercosis (80%) in those with intraocular cysticercosis in our study may indicate positive association between the two which needs further investigation. PMID- 27363959 TI - Diabetic retinopathy with or without clinically significant macular edema: The influencing factors. AB - INTRODUCTION: Diabetic retinopathy is the commonest micro vascular complication in patients with diabetes and remains a leading cause of blindness in people of working age group. OBJECTIVE: to determine the prevalence of clinically significant macular edema (CSME) and the influence of systemic risk factors Materials and methods: It is a hospital based comparative study conducted in 220 eyes of 110 diabetic patients. DR was graded according to International Clinical Diabetic Retinopathy Severity Scale and CSME was defined according to Early Treatment Diabetic Retinopathy Study (ETDRS) system. The patients were grouped as 1) CSME group (DR and CSME in one or both eyes) and 2) Non- CSME group(CSME in none of the eyes but with any grade of DR).Level of glycosylated hemoglobin (HbA1C), serum total cholesterol, triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL) and urine for albumin were studied in both groups. RESULTS: CSME was present in 36% of 110 patients. Poor glycemic control and high total cholesterol level showed positive association with CSME (p LESS THAN 0.05). LDL and TG levels were higher and HDL lower in CSME group. However, no statistical significance was found. CONCLUSION: The CSME is significantly associated with poorer glycemic control and elevated total cholesterol level. PMID- 27363960 TI - Cycloplegic influence on the accuracy of autorefractometer in myopic and hyperopic children. AB - OBJECTIVE: To investigate the cycloplegic effect on the accuracy of TOPCON AR RM 8000B autorefractometer in children. MATERIALS AND METHODS: This study included 219 children of age 3 to 16 years. Topical 1% cyclopentolate hydrochloride was instilled for attaining cycloplegia. The children with the refractive error of 0.75 Diopter or more were grouped as myopic and more than +1.00 Diopter as hyperopic. Autorefraction was performed in addition to manual refraction. We used the XLSTAT and Medcalc statistics software. RESULTS: Out of 219 children, 149 (68%) were emmetropic, 48 (22%) hyperopic and 22 (10%) myopic (n=70). Males and females constituted 29 (60.42%) and 19 (39.58%) respectively in hyperopic group where as 11 (54.55%) and 9 (45.45%) children were myopic. The means of ages of the children were 10.29 (+/- 2.96) and 13.14 (+/- 2.36) years in hyperopic and myopic groups respectively. Cycloplegic hyperopic and myopic autorefraction revealed mean sphere of +1.45 and -4.06 diopter with correlation coefficient of 0.95 and 0.99 respectively. Non-cycloplegic hyperopic autorefraction showed 74.2% sensitivity and 8.3% specificity at >-1 diopter with area under curve of 0.517 (p LESS THAN 0.0001). Cycloplegic hyperopic autorefraction showed 100% sensitivity and 97.1% specificity at >+1.85 diopter with accuracy of 0.616. Non-cycloplegic myopic autorefraction showed 100% sensitivity and 0.91% specificity at >-0.75 diopter with accuracy of 0.889. Cycloplegic myopic autorefraction showed 100% sensitivity and specificity at >-1.25 diopter with perfect accuracy. CONCLUSION: Non-cycloplegic hyperopic autorefraction failed to identify true negative cases. Cycloplegic autorefraction identified true positive cases and myopic autorefraction was relatively unaffected by cycloplegia. PMID- 27363961 TI - The indications for and the diagnostic yield of imaging in neuro-ophthalmic and orbital disorders. AB - Correction: On 7th June, the first author's name was changed FROM Eli Ranjitkar Pradan TO Eli Pradhan Introduction: Neuro-imaging is an important method of investigation in neuro- ophthalmic and orbital conditions. These investigations are expensive and time consuming. This study describes the diagnostic yield of neuroimaging in patients referred from neuro-ophthalmic services. OBJECTIVE: To evaluate the diagnostic yield of neuroimaging in patients with neuro-ophthalmic and orbital disorders. MATERIALS AND METHODS: Retrospective review of records of 188 patients referred to radiology department for imaging by the neuro-ophthalmic servicesat University Hospital Coventry. MAIN OUTCOME MEASURES: Imaging findings were defined to be significant, if it led to changes in patient management, and as relevant, if the abnormal imaging finding related to the patient's neuro ophthalmic complaint, examination finding or condition. The imaging findings were categorized into five groups based on significance and relevance as (a) significant and relevant, (b) significant and not relevant, (c) relevant and not significant, (d) not significant and not relevant, or (e) normal. The percentage of tests with a significant and relevant finding was defined as the diagnostic yield. The yield of the imaging test ordered was also analyzed based on neuro ophthalmic examination findings and indication for imaging. RESULTS: One hundred and eighty eight neuro-imaging studies were analyzed. The majority of this referral was made for evaluation of the orbit (30%) and the anterior visual pathway (22%), followed by motility disorder (16%) and cerebro vascular accidents (11%). Hemifacial spasm, nystagmus and headache were less common indications for imaging referral. Sixty-one (32.4%) had significant and relevant findings to the patient's neuro- ophthalmic condition. In the majority (33/61, 54%), imaging was done to evaluate the orbit. CONCLUSION: Among the imaging referral from neuro ophthalmic practice, request for evaluation of the orbit provides a higher diagnostic yield. PMID- 27363962 TI - Outcomes of implantable collamer lens V4 and V4c for correction of high myopia - a case series. AB - OBJECTIVE: To evaluate the visual outcomes and intraocular pressure changes after Visian Implantable Collamer Lens (ICL) implantation V4b and V4c (with centraflow technology) for correction of myopia. MATERIALS AND METHODS: A prospective, consecutive, comparative interventional case series of V4b and V4c ICL implantation done for correction of high myopia (>-6 diopter D) in patients unsuitable for laser vision correction. The outcome measures that were evaluated included preoperative and postoperative uncorrected distant visual acuity (UDVA), best spectacle corrected distant visual acuity (CDVA), endothelial cell count (ECC), presence of lens opacification, intraocular pressure (IOP) and ICL vaulting. A follow-up of upto 1 year was done. A questionnaire was given at the end of follow-up period. RESULTS: A total of 30 eyes (24.56+/-4.8 years) underwent V4b ICL implantation (10 non-toric, 20 toric ICL-TICL) with intraoperative peripheral iridectomy (PI) and 34 eyes (26.13+/-3.8 years) had implantation of V4c ICL with centraflow (12 non-toric, 22 TICL). The mean preoperative manifest spherical equivalent (MSE) was 8.98+/-2.8 D and 9.24+/-2.4 D in the V4b and V4c groups respectively which reduced to postoperative values of -0.28+/-1.3 D and -0.19+/-1.18 D respectively. The mean preoperative astigmatism was -1.8+/-1.2 diopter cylinder (Dcyl) and -1.9+/-1.6 Dcyl which respectively reduced to -0.8+/-0.8 Dcyl and -0.9+/-0.3 Dcyl. At the end of 1 year follow up, mean ECC loss was 7.6% and 7.1%, mean vault was 583.12+/-231.12 MU and 602+/ 241.24MU respectively in the V4b and V4c groups. Anterior subcapsular opacities were present in 6.66% and 2.94% of eyes with V4b and V4c groups respectively. Two eyes from both V4b (10%) and V4c (8.33%) had rotation of more than 30 degrees and required re-rotation surgery done successfully. Two eyes (6.66%) with V4b ICL implantation had high postoperative IOP (>35 mm Hg) and required Nd:Yag laser iridotomy later done with successful control of IOP. The safety indices were 1.12 and 1.15 and efficacy indices were 1.5 and 1.6 in the V4b and V4c groups respectively at the end of 1 year. The most common visual complaint was glare and haloes in 24% and 27% in the two groups respectively. However, they were not annoying enough to cause visual disability. CONCLUSIONS: Both V4b and V4c Visian ICL implantations are comparable in terms of visual outcome and safety profile for correction of high myopia. However, V4c ICL offers these advantages without the requirement of an additional PI. PMID- 27363963 TI - Amniotic membrane transplantation (AMT) without the use of sutures/fibrin glue. AB - INTRODUCTION: Amniotic membrane transplantation (AMT) has been used for a wide variety of ocular surface problems. Current techniques for the AMT involve suturing of the graft or patch over the ocular surface or use of fibrin glue. OBJECTIVE: To describe a new sutureless technique of amniotic membrane transplantation (AMT) without the use of sutures/fibrin glue. MATERIALS AND METHODS: Amniotic membrane transplantation as overlay or patch was done in fourteen eyes of eight patients with severe dry eye due to Stevens Johnson syndrome for ocular surface reconstruction, promotion of epithelization, reduction of inflammation and symptomatic relief from dry eye. In this new technique of amniotic membrane transplantation, we mount the amniotic membrane with its epithelial side up on a conformer and place it on the ocular surface without applying any sutures. CONCLUSION: In all the fourteen eyes of eight patients operated at our centre, the amniotic membrane take up was satisfactory, with significant reduction of inflammation and symptomatic relief from dry eye. This is a simple, fast effective technique with surgical outcomes comparable to amniotic membrane transplantation using sutures/ fibrin glue. PMID- 27363964 TI - Occult intraocular foreign body presenting as squint. AB - BACKGROUND: We report a case of an occult retained intraocular foreign body detected four years after "forgotten" trauma. CASE: A 23-year-old male presented with exodeviation and was referred as a case of epiretinal membrane. The anterior segment and adnexa were normal. Fundus examination revealed macular epiretinal membrane. An occult foreign body was localized in the retinal periphery. Imaging confirmed the diagnosis. OBSERVATION: Squint and epiretinal membrane may develop in cases of occult foreign bodies and may be the presenting sign years after trauma. CONCLUSION: A careful history of ocular trauma and thorough examination, complemented by radio imaging when needed, should be done in atypical cases. PMID- 27363965 TI - Isolated rectus muscle rupture following trauma. AB - BACKGROUND: Isolated rectus muscle ruptures are rare ophthalmic emergencies which may result in permanent diplopia. OBJECTIVE: To highlight updates on clinical features, surgical treatment options and potential complications for isolated inferior rectus ruptures. CASE: A 39-year-old man came to our emergency department complaining of diplopia and upward deviation of the right eye after experiencing an animal injury. Extraocular movements were limited in the right eye in the downgaze position. The alternate prism and cover test, both at distance and near testing, showed hypertropia of 40 prism diopters (PD) of the right eye. The right eye had periorbital swelling and conjunctival haematoma. An inferior rectus rupture repair was performed under local anesthesia and monitored sedation. Follow-up examination revealed a 20 PD hypertropia, causing diplopia in all gazes. A second surgical intervention was planned six months after the initial surgery, an inferior rectus 6 mm resection was performed, after which orthophoria was achieved in the primary position both at distance and near testing. PMID- 27363966 TI - A case of transorbital intracranial injury presenting with subtle neurological deficit. AB - BACKGROUND: Ocular trauma is a major cause of visual morbidity. OBJECTIVE: To present a rare case of transorbital intracranial injury extending up to the left internal carotid artery (ICA) with no other systemic neural deficit except for the ocular manifestations. CASE: A 14-year-old female presented to our out patient department (OPD) with the history of trauma to her left eye with stumps of bamboo shoots secondary to a fall injury. Examination and investigations revealed a foreign body extending from left inferior conjunctival fornix into the intracranial cavity, occluding the various segments of left ICA. The patient subsquently underwent craniotomy and foreign body removal by a combined team of neurosurgeons and ophthalmologists. On discharge, the patient had slight improvement in extraocular motility of her left eye. However the trauma rendered the affected eye, non-seeing. CONCLUSION: The intracranial extent of a foreign body entering the cranium via the transorbital route cannot be judged merely by the clinical findings of the nervous system and ocular examination. These patients need timely management by the combined effort of ophthalmologists, neurosurgeons and radiologists. PMID- 27363967 TI - Unilateral visual loss due to central retinal artery occlusion with total ophthalmoplegia following cervical spine surgery in prone position. AB - BACKGROUND: Blindness after spinal surgery is a rare complication, but it is serious, irreversible and incurable. Central retinal artery occlusion (CRAO) is rare after spinal surgery and ophthalmoplegia is even rarer. CASE: A 52-year-old male patient complained of loss of vision in right eye immediately after cervical spine surgery. On examination, the patient's visual acuity in right eye was absent perception of light. Right eye pupil was dialated and relative afferent pupillary defect (RAPD) was present. Extraocular movements were absent in all gazes in right eye. Intra-ocular pressure (IOP) was 26 mmHg in right eye and 16 mmHg in the left. Posterior segment examination revealed blurred disc margin with ischemic whitening of retina, thin and attenuated retinal arterioles and a central cherry red spot in right eye. Left eye was essentially normal. OBSERVATIONS: The causal factors of blindness in the patient were likely ischemia of the retina after venous congestion or temporary arterial occlusion resulting from changes in pressure to the tissues of the orbit. Factors including prolonged prone positioning with head end dependent position and possibility of orbital compression by the headrest could have contributed to impaired venous drainage, increase in IOP and reduction in perfusion pressure. CONCLUSION: Loss of vision post spinal surgery is a rarest of complication yet grave and irreversible. Because the problem involves mainly prone positioning of the patient, an appropriate position should be found so that facial and ocular compression can be avoided. PMID- 27363968 TI - Management of childhood glaucoma in Sturge Weber Syndrome: A challenge. AB - BACKGROUND: Sturge-Weber syndrome (SWS) is a rare congenital neuro- oculo- cutaneous disorder. Glaucoma is one of the ocular abnormalities associated with it. Management of glaucoma in SWS is challenging. OBJECTIVE: To report surgical and visual outcome of trabeculectomy in bilateral glaucoma in Sturge-Weber syndrome and the challenges encountered in its management. CASE DESCRIPTION: A six-year-old girl presented with gradually progressive increase in size of both the eyes associated with watering, photophobia and diminution of vision since birth. On examination she was diagnosed to have bilateral SWS with glaucoma, refractive to antiglaucoma medications. She underwent trabeculectomy with intraoperative use of 5- FU. The post operative period was complicated with choroidal effusion in both the eyes with shallow anterior chamber. In the second post operative day, the right eye anterior chamber re- formation was done with ringer lactate solution. There was spontaneous resolution of choroidal effusion with normalization of intraocular pressure with no adverse effect on visual acuity within one week. CONCLUSION: Treatment of glaucoma associated with Sturge Weber syndrome is challenging. When planning surgical intervention an increased risk of choroidal effusion associated with it, should be kept in mind. PMID- 27363969 TI - Penetrating ocular fish hook injury: a case report. AB - BACKGROUND: Fishing is a popular rural recreational activity. Fortunately, penetrating ocular injuries with fish hooks are rare. These injuries are usually caused by fish hook prongs penetrating the ocular tissues. We report a rare case of penetrating fish hook injury to the globe and its successful surgical management. CASE: A 12- year-old female child was referred to the causality with a fish hook embedded in her right eye. She sustained the injury while fishing with her father. The fish hook had penetrated the globe obliquely. The hook was removed via its entrance wound under general anesthesia. Subsequently the child developed traumatic cataract which was operated with a final visual outcome of 6/12. CONCLUSION: Visual prognosis can be profoundly affected by the initial management. Prompt surgical intervention as done in our case is recommended to prevent significant visual loss. Keywords Fishhook; penetrating ocular injury; traumatic cataract. PMID- 27363970 TI - Dynamic Magnetic Resonance Imaging- a sensitive tool in managing consecutive exotropia. AB - BACKGROUND: Proper evaluation and accurate diagnosis are crucial in managing a case of strabismus. OBJECTIVE: Report a case of prolonged large angle complicated consecutive exotropia where dynamic Magnetic Resonance Imaging helped us to diagnose and simplify the management plan. CASE: A 19-year-old male presented with outward deviation of both eyes for last 16 years with right face turn, without diplopia and trauma. However, he had history of two consecutive squint surgeries, a month apart, at the age of 3 years. OBSERVATION: Visual acuity (best corrected) in the right and left eye was 6/36 and 6/6 respectively. Extraocular movements revealed minus (-) 4 adduction deficits in the left eye with right eye suppression. Prism Alternate Cover Test (PACT) showed 65 prism diopter (PD) base in (BI), for primary and near gazes with lateral incommitance and without any pattern. Forced Duction Test (FDT) showed restriction of the left lateral rectus. Dynamic Magnetic Resonance Imaging revealed posterior insertion of the left medial rectus with thinning of the tendinous insertion of the left lateral and medial rectus in neutral position. On adduction of left eye, there was slight increased bulk of the left medial rectus. Medial Rectus (MR) advancement 5.5 mm and Lateral Rectus (LR) recession 9mm was done. Repeat FDT showed improvement in resistance. After 3 month, the patient had excellent outcome with 5 PD primary position exotropia and 2 units of improvement in left eye adduction. CONCLUSION: Precise workup and appropriate investigation decreases the undue interventions with excellent outcome in a case of large angle consecutive XT. Keywords Consecutive exotropia; dynamic MRI; esotropia; medial rectus advancement; slipped muscle. PMID- 27363971 TI - Orbital Cysticercosis - masquerading as preseptal cellulitis with ptosis. AB - We are sharing a case of orbital cysticercosis,which presented to us initially with simple ptosis and later on with upper lid inflammation and restricted ocular motility in upgaze. Human cysticercosis, a parasitic infection caused by Cysticercus cellulosae, the larval form of the cestode, Taenia solium, is a benign infection of the subcutaneous tissues, inter-muscular fascia, muscles and other organs. Though it exists worldwide, it is more prevalent in the developing countries of Latin America, Asia and Africa, especially in areas where under cooked pork is consumed regularly (Pushker et al, 2001). However, 5 year study of 33 cases of Ocular/Adnexal cysticercosis showed seventy percent of patients were of low socioeconomic group and 70% were strictly vegetarians (Atul et al, 1995). The clinical manifestation of orbital cysticercosis is entirely different from neuro-cysticercosis or cysticercosis of other parts of body. Diagnosis of cysticercosis is mainly based on highly specific radiological signs and history of exposure in endemic areas. PMID- 27363972 TI - By how much could screening by primary human papillomavirus testing reduce cervical cancer incidence in England? AB - Objective The replacement of cytology with human papillomavirus testing as the primary cervical screening test in England is imminent. In light of newly available evidence, we revised our previous estimates of the likely impact of primary human papillomavirus testing on incidence of cervical cancer. Method and results Using screening data on women aged 25-64 diagnosed with cervical cancer in England between 1988 and 2012, we previously reported that 38.8% had a negative test six months to six years prior to diagnosis. However, not all of these cancers would be prevented by human papillomavirus testing: for 1.0% the human papillomavirus positive test would come too late (within 18 months of diagnosis) to make a difference; 7.6% will have a negative human papillomavirus test (based on 79.9% sensitivity of human papillomavirus testing in cytology negative women); and 2.0% will develop cancer despite a positive human papillomavirus test. Additionally, we estimate that some women (equivalent to 4.3% of current incidence) whose cancers are currently prevented by cytology based screening will have a false-negative human papillomavirus test. Conclusion Overall, we estimate that 23.9% (95% CI: 19.3-27.6%) of current cases in women invited for screening could be prevented. Based on 2013 cancer incidence statistics, absolute numbers could be reduced by 487 (95% CI 394 to 563) or 3.4 (95% CI 2.8 to 4.0) per 100,000 women per year. PMID- 27363973 TI - An outbreak of a possibly new Salmonella enterica subspecies enterica serovar with the antigenic formula 11:z41:e,n,z15, Greece, March to May 2016: preliminary results. AB - Eleven Salmonella spp. isolates with the antigenic type 11:z41:e,n,z15 - not referred to in the 9th edition of the White-Kauffman-Le Minor Scheme - were identified at the National Reference Laboratory for Salmonella in Greece. Their pulsed-field gel electrophoresis profiles were indistinguishable. No apparent epidemiological link has yet been identified; the results of a case-case study are pending. PMID- 27363974 TI - Treatment for cirrhotic ascites. AB - Common complications of decompensated liver cirrhosis are esophageal varices, hepatic encephalopathy and ascites. After the onset of complications, the prognosis worsens. In patients with ascites, the 5-year mortality rate is 44%. Furthermore, hyponatremia, spontaneous bacterial translocation and hepatorenal syndrome also greatly worsen the prognosis. Effective treatment of cirrhotic ascites improves the quality of life and survival rate. Recently, the newly produced diuretic, tolvaptan (vasopressin V2 receptor antagonist), was reported to be effective in the treatment of refractory ascites in liver cirrhosis; however, there has not been an associated positive effect on the prognosis. There are various types of treatment for ascites, such as large-volume paracenteses, a cell-free and concentrated ascites reinfusion therapy, a transjugular intrahepatic portosystemic shunt, and a peritoneo-venous shunt. Although they improve the prognosis, liver transplantation remains the ultimate form of treatment. The present article discusses the therapeutic management of cirrhotic ascites. PMID- 27363975 TI - Pancreatic Cancer Survival Increases with Chemo Combo. AB - For patients able to have surgery for pancreatic cancer, the adjuvant use of gemcitabine plus capecitabine, instead of gemcitabine alone, leads to a significant improvement in 5-year survival, according to results of the ESPAC-4 trial. The finding will likely change the standard of care for these patients. PMID- 27363976 TI - A Rare Cause of a Cerebrovascular Accident in a Renal Transplant Recipient: Corpus Callosum Infarction. AB - Renal transplantation is a life-saving procedure in patients with end-stage renal failure. Advanced surgical procedures and enhanced perioperative care favorably affect the progression of the disease. Despite these advances, neurological complications are important sources of mortality and morbidity. The rate of neurological complications after renal transplantation has been reported as 10 21% by various studies. Here we report a case with corpus callosum infarction in a 39-year-old renal transplant recipient. PMID- 27363977 TI - Hexokinase 2 in colorectal cancer: a potent prognostic factor associated with glycolysis, proliferation and migration. AB - BACKGROUND: It is well known that proliferating carcinoma cells preferentially use aerobic glycolysis rather than oxidative phosphorylation for energy production. Hexokinase 2 (HK2) plays a pivotal role in the glycolytic pathway. Previous studies have demonstrated that HK2 activity is markedly increased in various malignant neoplasms, but the clinical and biological significance of HK2 remain largely unclear in the colorectal carcinoma. PATIENTS AND METHODS: We performed immunohistochemistry for HK2 in 195 colorectal carcinoma tissues. We also used HCT8 and HT29 colon carcinoma cells in in vitro studies. RESULTS: HK2 immunoreactivity was detected in 100 out of 195 (51%) colorectal carcinoma tissues, and the immunohistochemical HK2 status was significantly associated with tumor size, depth of invasion, liver metastasis and TNM stage in these cases. Moreover, the HK2 status was significantly associated with increased incidence of recurrence and overall mortality of the patients, and multivariate analyses demonstrated that HK2 status was an independent prognostic factor for both disease-free and overall survival. Subsequent in vitro experiments revealed that both HCT8 and HT29 colon carcinoma cells transfected with specific siRNA for HK2 significantly decreased the lactate production, proliferation activity and migration property. CONCLUSION: These results suggest that HK2 plays important roles in the glycolytic, proliferation and migration properties of colorectal carcinoma and, therefore, HK2 status is a potent worse prognostic factor in colorectal cancer patients. PMID- 27363978 TI - Interventional Pain Management Approaches for Control of Chronic Pancreatic Pain. AB - OPINION STATEMENT: Treatment of persistent pain from chronic pancreatitis historically was difficult to treat. For years, focus was on opioid and other analgesics and psychological treatments. Recent studies provided evidence for decrease in analgesic intake and pain scores after properly conducted sympathetic blocks (celiac, splanchnic nerve blocks). These therapies should be considered as parts of a multimodal analgesic strategy. Animal studies suggest that spinal cord stimulation suppresses visceral hyperalgesia. Large case series of spinal cord stimulation demonstrated a significant pain relief in patients with chronic pancreatitis. Given the limitations of conservative and surgical treatments for chronic visceral pain, spinal cord stimulation may be a very useful therapeutic option. PMID- 27363979 TI - Endoscopy in the Elderly: a Cautionary Approach, When to Stop. AB - OPINION STATEMENT: Performing endoscopic procedures in the elderly carries known enhanced risk compared to the general population. Weighing the benefits against the risks is easy when a patient is in immediate danger, but a gray area arises in screening protocols in an elderly patient of average risk. In this review, we compare national and international guidelines in average risk screening procedures (colonoscopic colorectal screening, Barrett's surveillance) to find consensus for screening practice in the elderly. With minor differences between societal guidelines, it is widely agreed that 75 years is the appropriate age to begin to weigh risks and benefits according to a patient's state of health and comorbidities. For colorectal screening, most guidelines advocate complete cessation of screening after the age of 85 years. Such consensus must take into account an aging population where patients are living healthier for longer and thus may be appropriate candidates for screening procedures even if beyond designated ages of screening cessation. PMID- 27363980 TI - It is unnecessary to completely mobilize the kidney in retroperitoneoscopic renal pedicle lymphatic disconnection for intractable chyluria. AB - PURPOSE: To compare the efficacy and safety of two approaches in retroperitoneoscopic renal pedicle lymphatic disconnection (RRPLD) for intractable chyluria: completely or partly mobilize the kidney. MATERIALS AND METHODS: Retrospectively reviewed the clinical data of 77 patients, who underwent RRPLD because of intractable chyluria in our institution. We mobilized the whole affected kidney in 22 patients during the operation, but only dissected the lower part in other 55 patients. Operative time, blood loss, visual analog scale (VAS) score, postoperative bed rest, postoperative hospital stay, recurrence, intraoperative and postoperative complications were compared between the two groups. RESULTS: All operation was successful, and none convert to open. The chyluria was resolved immediately after surgery. Compared with completely mobilized RRPLD (CMR), partly mobilized RRPLD (PMR) was superior in terms of operative time (132.91 +/- 35.65 vs. 91.73 +/- 24.14 min), blood loss (35.68 +/- 8.21 vs. 25.09 +/- 7.41 ml), VAS score (4.63 +/- 0.44 vs. 2.34 +/- 0.80), postoperative bed rest (3.36 +/- 0.49 vs. 1.80 +/- 0.85 days) and hospital stay (6.77 +/- 1.57 vs. 4.98 +/- 1.89 days). Compilations occurred in three patients in CMR group and two in PMR. Recurrence was confirmed by cystoscopy in three patients during 3-103-month follow-up, CMR group with 1 and PMR with 2. CONCLUSION: In our study, we found PMR was equally effective and safe as CMR. Moreover, it is more minimally invasive, painless and economical. Therefore, we believe it is unnecessary to completely mobilize the kidney in RRPLD for intractable chyluria. PMID- 27363982 TI - Methods used to measure postoperative insulin resistance. PMID- 27363981 TI - Varicocele percutaneous embolization outcomes in a pediatric group: 7-year retrospective study. AB - PURPOSE: Percutaneous embolization and surgical repair are the current treatment options for varicocele, but determining method superiority remains controversial. In this retrospective study, we evaluate the technical success, complication and recurrence rates following percutaneous embolization in a pediatric group, which were compared to reported outcomes for surgical repairs. METHODS: Thirty children treated for percutaneous varicocele embolization were recruited. The side and grade of varicocele, symptoms, testicular asymmetry, mean recurrence time, total radiation dose and complications were evaluated. Recurrence and follow-up complications due to embolization were also reviewed. RESULTS: The venography showed retrograde filling of the internal spermatic vein with the identification of aberrantly fed vessels in 23 % of patients. None of the patients suffered from procedure complications except one who had venous injury which was treated with a sclerosing agent. The technical success rate was 93 % (28 patients) with a recurrence rate of 13 % (4 patients). Interestingly, the mean radiation dose used was 862.5 uGy m(2), 3 times lower than abdominal CT. CONCLUSION: Considering the intravascular nature of embolization, which aims to avoid testicular artery and spermatic cord damage (difficult to avoid with the surgical method), and consequently a lower complication rate, along with the same success rate and recurrence rate, our study supports that embolization is a superior method to surgical interventions. PMID- 27363983 TI - Daratumumab: a first-in-class CD38 monoclonal antibody for the treatment of multiple myeloma. AB - Daratumumab is a human monoclonal antibody that targets CD38, a cell surface protein that is overexpressed on multiple myeloma (MM) cells. Preclinical studies have shown that daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC), antibody-dependent cell mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and apoptosis. Given the encouraging efficacy and acceptable safety profile of daratumumab demonstrated in clinical trials, daratumumab has emerged as a novel treatment option for myeloma and became the first monoclonal antibody approved by the FDA for the treatment of MM. PMID- 27363984 TI - Endothelial nitric oxide synthase gene polymorphisms are associated with sensitization to seasonal aeroallergens in asthmatic children. AB - BACKGROUND: Childhood asthma phenotype is the consequence of interaction between environment and genetic factors. Nitric oxide (NO) formation is affected by polymorphisms in nitric oxide synthase (NOS) enzymes, which play a significant role as inflammatory factors in the airways. This study was undertaken to estimate the correlation of -786C>T and 894G>T polymorphisms of the eNOS gene with the sensitization of asthmatic children to common aeroallergens. METHODS: A total of 193 asthmatic children and 96 healthy controls, who were of Mediterranean origin, living in the same geographical area, were enrolled in the study. 894G>T and -786T/C polymorphisms of the eNOS gene were analyzed using a PCR-RFLP method. RESULTS: The 894GG genotype was more frequent (68.6%) in children with asthma sensitized to Oleaeuropaea than in those with asthma non sensitized (43.0%) (P=0.004). Likewise, -786TT genotype frequency was higher in children with asthma sensitized to Oleaeuropaea (51.0%) than in those with asthma nonsensitized (31.7%) to this allergen (P=0.035). For the aeroallergens Parietariajudaica and mixed grass, the frequency of -786C allele carriage was associated with protection from sensitization to Parietariajudaica and mixed grass in asthmatic children (P=0.021 and P=0.017, respectively). In the healthy control group, the genotype frequencies for these polymorphisms were similar to genotype frequencies of children with asthma non-sensitized to these three specific aeroallergens. CONCLUSION: In children with asthma, 894G>T and -786T/C polymorphisms of the eNOS gene were correlated with sensitization to common seasonal aeroallergens. PMID- 27363985 TI - Non-pharmacological management of abdominal pain-related functional gastrointestinal disorders in children. AB - BACKGROUND: Abdominal pain-related functional gastrointestinal disorder (AP-FGID) comprises of 4 main conditions: functional dyspepsia, irritable bowel syndrome, abdominal migraine and functional abdominal pain. AP-FGIDs are diagnosed clinically based on the Rome IV criteria for FGIDs of childhood. There is limited evidence for pharmacological therapies. DATA SOURCES: This review article discusses nonpharmacological management of AP-FGID based on the current literature including systematic reviews, randomized controlled trials, cohort and case control studies. We aim to provide a comprehensive overview on the available evidence for the pediatricians and pediatric gastroenterologists involved in managing children with AP-FGID. RESULTS: Managing AP-FGIDs can be challenging. This should follow a stepwise approach with focused history, identification of "red flag" signs and symptoms, physical examination and investigations done following initial consultation. Family needs explaining that there is nothing seriously wrong with the child's abdomen. This explanation and reassurance can achieve symptom control in large number of cases. Non-pharmacological interventions are delivered through lifestyle and dietary changes and bio psychosocial therapies. Dietary interventions vary depending on the type of AP FGID. Bio-psychosocial therapies such as hypnotherapy, cognitive behavioral therapy and yoga aim at stress reduction. CONCLUSION: There is increasing evidence for use of non-pharmacological interventions in children with APFGID. PMID- 27363986 TI - A high-fat high-energy diet influences hepatic CYP3A expression and activity in low-birth-weight developing female rats. AB - BACKGROUND: The objective of this study was to investigate the effects of a high fat, high-energy (HFHE) diet on the hepatic expression of CYP3A in low birthweight developing female rats. METHODS: Pregnant rats were divided into nourished and undernourished groups. The offspring of the nourished rats were defined as the normal-birth-weight (NBW) group, and those of undernourished rats were defined as the low-birth-weight (LBW) group. According to their birth weights and diets, the rats were subdivided into the following four groups: NBW normal diet (NN) group; NBW-HFHE (NH) group; LBW-normal diet (LN) group; and LBW HFHE (LH) group. Liver samples were isolated on days 3, 7, 14, 21, 28, 56 and 84 after birth. RESULTS: The CYP3A1 mRNA levels in the LH group on days 3, 56 and 84 were significantly higher than those of the NN group (P<0.05). CYP3A1 expression was significantly higher in the LH group than that in the NH group on days 21, 28 and 84 (P<0.05). CYP3A1 mRNA expression was higher in the LH group than that in the LN group on days 3 and 21 (P<0.05). No zonal CYP3A1 expression pattern was observed in the LH developmental group. The LH group had significantly higher mean activity than the LN group on days 7, 14, 28 and 56. CONCLUSION: Our results indicated that an HFHE diet can result in alterations of CYP3A expression in a developmental LBW rat model. PMID- 27363987 TI - [Employment, family and health in men of working age in Germany : Results of the GEDA studies 2009-2012]. AB - BACKGROUND: Today's men want to participate in their children's upbringing more than in the past, but they are heavily involved in their occupation at the same time. This article describes the significance of parenthood, partnership and occupation in relation to health and health behaviours among men of working age in Germany. DATA: We summarised data from the "German Health Update" (GEDA) studies conducted in 2009, 2010 and 2012. Data on 18,465 men aged 18-64 years were available, 11,429 of which were living with children. We included mental health problems, general health awareness, sports activity and smoking as outcomes. RESULTS: Full-time employees working more than 48 h per week and unemployed persons had mental health problems more frequently (OR 1.44 and 2.35, p < 0.05) than full-time employees working 48 h or fewer. Similar associations can be shown for health awareness, physical activity and smoking. Concerning partnership and parenthood, the associations were considerably weaker: men living together with children and a partner in the household were overall less burdened and their behaviour was also healthier than single men without children. After simultaneous consideration of employment status, parenthood and partnership, our results show that the unemployed and employees with long working hours were the most burdened. DISCUSSION: The results provide supporting evidence regarding health problems of men in Germany due to unemployment and long working hours that are of importance for their health whether they are living with a partner and/or with children or not. The association between health and occupation was stronger than between health and fatherhood or partnership. PMID- 27363988 TI - Influences of Aerobic Dance on Cognitive Performance in Adults with Schizophrenia. AB - Cognitive impairment is one of the core features of schizophrenia. This study examined the influences of an aerobic dance programme on the cognitive functions of people with schizophrenia. A quasi-experimental matched-control design was applied. The experimental group (n = 17) participated in a 60-minute aerobic dance group class three times a week for 3 months. The control group (n = 19) participated in colouring and handwriting activities. Cognitive functions were measured before and after the interventions for both groups. The intervention group experienced significant improvements in processing speed, memory and executive function, whereas no significant changes were noted in any measures in the control group. While there were no significant between-group differences, the data showed approximately medium effect sizes that favoured the intervention group in regard to processing speed (Cohen's d = 0.51), memory (d = 0.35-0.41) and the spontaneity and fluency aspects of executive function (d = 0.51). While the small sample size and lack of randomization were the primary methodological shortcomings, this study provides preliminary results supporting aerobic dance as an adjunct activity-based intervention to improve cognitive functions in people with schizophrenia. More rigorous studies are needed to validate the findings. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27363989 TI - Coagulation Factor XIIIA Subunit Missense Mutations Affect Structure and Function at the Various Steps of Factor XIII Action. AB - Inherited defects of coagulation Factor XIII (FXIII) can be categorized into severe and mild forms based on their genotype and phenotype. Heterozygous mutations occurring in F13A1 and F13B genes causing mild FXIII deficiency have been reported only in the last few years primarily because the mild FXIII deficiency patients are often asymptomatic unless exposed to some kind of a physical trauma. However, unlike mutations causing severe FXIII deficiency, many of these mutations have not been comprehensively characterized based on expression studies. In our current article, we have transiently expressed 16 previously reported missense mutations detected in the F13A1 gene of patients with mild FXIII deficiency and analyzed their respective expression phenotype. Complimentary to expression analysis, we have used in silico analysis to understand and explain some of the in vitro findings. The expression phenotype has been evaluated with a number of expression phenotype determining assays. We observe that the mutations influence different aspects of FXIII function and can be functionally categorized on the basis of their expression phenotype. We identified mutations which even in heterozygous form would have strong impact on the functional status of the protein (namely mutations p.Arg716Gly, p.Arg704Gln, p.Gln602Lys, p.Leu530Pro, p.His343Tyr, p.Pro290Arg, and p.Arg172Gln). PMID- 27363990 TI - The cytostome-cytopharynx complex of Trypanosoma cruzi epimastigotes disassembles during cell division. AB - The cytostome-cytopharynx complex is the main site for endocytosis in epimastigotes of Trypanosoma cruzi It consists of an opening at the plasma membrane surface - the cytostome - followed by a membrane invagination - the cytopharynx. In G1/S cells, this structure is associated with two specific sets of microtubules, a quartet and a triplet. Here, we used electron microscopy and electron tomography to build 3D models of the complex at different stages of the cell cycle. The cytostome-cytopharynx is absent in late G2 and M phase cells, whereas early G2 cells have either a short cytopharynx or no visible complex, with numerous vesicles aligned to the cytostome-cytopharynx microtubules. The microtubule quartet remains visible throughout cell division (albeit in a shorter form), and is duplicated during G2/M. In contrast, the microtubule triplet is absent during late G2/M. Cells in cytokinesis have an invagination of the flagellar pocket membrane likely to represent early stages in cytostome cytopharynx assembly. Cells in late cytokinesis have two fully developed cytostome-cytopharynx complexes. Our data suggest that the microtubule quartet serves as a guide for new cytostome-cytopharynx assembly. PMID- 27363991 TI - Inhibiting High-Mobility Group Box 1 (HMGB1) Attenuates Inflammatory Cytokine Expression and Neurological Deficit in Ischemic Brain Injury Following Cardiac Arrest in Rats. AB - Cardiac arrest (CA), if untreated for more than 5 min, can induce severe brain damage, the underlying mechanism of which is still unclear. Previous studies have indicated that high-mobility group box 1 (HMGB1), a nuclear protein implicated in several inflammatory disorders, is involved in the inflammatory processes following brain ischemia. However, the role of HMGB1 in brain dysfunction after CA is yet to be determined. In a rat CA model, HMGB1 protein expression was higher at 1, 3, and 7 days post-CA, compared to that in naive and sham-treated rats. Following injection of HMGB1 antibody (anti-HMGB1) into the cerebral ventricles, neurological deficit scores were significantly decreased in the CA group as compared to that in the naive and sham group. Nissl staining showed significant neuronal loss in the hippocampal CA1 region following CA, which was significantly attenuated by anti-HMGB1-treatment (10 and 50 MUg) in comparison with the vehicle-injected control. CA induced a significant increase in the levels of the cytokine interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) in the hippocampus as revealed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Treatment with anti-HMGB1 significantly inhibited IL-1beta and TNF-alpha expression. Our study suggests that HMGB1 contributes significantly to CA-induced brain dysfunction and that inhibiting HMGB1 function and expression may be an effective therapeutic approach to CA-induced ischemic brain injury. PMID- 27363992 TI - Capturing the diversity of the human gut microbiota through culture-enriched molecular profiling. AB - BACKGROUND: The human gut microbiota has been implicated in most aspects of health and disease; however, most of the bacteria in this community are considered unculturable, so studies have relied on molecular-based methods. These methods generally do not permit the isolation of organisms, which is required to fully explore the functional roles of bacteria for definitive association with host phenotypes. Using a combination of culture and 16S rRNA gene sequencing, referred to as culture-enriched molecular profiling, we show that the majority of the bacteria identified by 16S sequencing of the human gut microbiota can be cultured. METHODS: Five fresh, anaerobic fecal samples were cultured using 33 media and incubation of plates anaerobically and aerobically resulted in 66 culture conditions for culture-enriched molecular profiling. The cultivable portion of the fecal microbiota was determined by comparing the operational taxonomic units (OTUs) recovered by 16S sequencing of the culture plates to OTUs from culture-independent sequencing of the fecal sample. Targeted isolation of Lachnospiraceae strains using conditions defined by culture-enriched molecular profiling was carried out on two fresh stool samples. RESULTS: We show that culture-enriched molecular profiling, utilizing 66 culture conditions combined with 16S rRNA gene sequencing, allowed for the culturing of an average of 95 % of the OTUs present at greater than 0.1 % abundance in fecal samples. Uncultured OTUs were low abundance in stool. Importantly, comparing culture-enrichment to culture-independent sequencing revealed that the majority of OTUs were detected only by culture, highlighting the advantage of culture for studying the diversity of the gut microbiota. Applying culture-enriched molecular profiling to target Lachnospiraceae strains resulted in the recovery of 79 isolates, 12 of which are on the Human Microbiome Project's "Most Wanted" list. CONCLUSIONS: We show that, through culture-enriched molecular profiling, the majority of the bacteria in the human gut microbiota can be cultured and this method revealed greater bacterial diversity compared to culture-independent sequencing. Additionally, this method could be applied for the targeted recovery of a specific bacterial group. This approach allows for the isolation of bacteria of interest from the gut microbiota, providing new opportunities to explore mechanisms of microbiota-host interactions and the diversity of the human microbiota. PMID- 27363993 TI - Gland and Zonal Segmentation of Prostate on T2W MR Images. AB - For many years, prostate segmentation on MR images concerned only the extraction of the entire gland. Currently, in the focal treatment era, there is a continuously increasing need for the separation of the different parts of the organ. In this paper, we propose an automatic segmentation method based on the use of T2W images and atlas images to segment the prostate and to isolate the peripheral and transition zones. The algorithm consists of two stages. First, the target image is registered with each zonal atlas image then the segmentation is obtained by the application of an evidential C-Means clustering. The method was evaluated on a representative and multi-centric image base and yielded mean Dice accuracy values of 0.81, 0.70, and 0.62 for the prostate, the transition zone, and peripheral zone, respectively. PMID- 27363994 TI - Clinical-Pathological Conference Series from the Medical University of Graz : Case No 159: 52-year-old patient with psoriasis and arthralgia of the finger joints. PMID- 27363995 TI - Portal vein resection in advanced pancreatic adenocarcinoma: is it worth the risk? AB - INTRODUCTION: Portal vein resection represents a viable add-on option in standard pancreaticoduodenectomy for locally advanced ductal pancreatic adenocarcinoma, but is often underused as it may set patients at additional risk for perioperative and postoperative morbidity and mortality. We aimed to review our long-term experience to determine the additive value of this intervention for locally advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: Single, university surgical center audit over a 13-year period; cohort comprised 221 consecutive patients undergoing pancreatic resection; in 47 (21 %) including portal vein resection. Predictors for short- and long-term survival were assessed via multivariate logistic and Cox regression. RESULTS: Baseline and perioperative characteristics were similar between the two groups. However, overall skin-to skin times, intraoperative transfusion requirements as the need for medical inotropic support were higher in patients undergoing additional portal vein resection (p < 0.0001; p = 0.001 and p = 0.03). Postoperative complication rates were 34 vs. 35 % (p = 0.89), 14 patients (5 % vs. 11 %; p = 0.18) died in hospital. An American Society of Anesthesiologists Score >2 was the only independent predictor for in-hospital mortality (OR 10.66, 95 % CI 1.24-91.30). Follow-up was complete in 99.5 %, one-year survival was 59 % vs. 70 % and five year overall survival 15 % vs. 12 % with and without portal vein resection, respectively (Log rank: p = 0.25). For long-term outcome, microvascular invasion (HR 2.03, 95 % CI 1.10-3.76) and preoperative weight loss (HR 2.17, 95 % CI 1.31 3.58) were independent predictors. CONCLUSION: Despite locally advanced disease, patients who underwent portal vein resection had no worse perioperative and overall survival than patients with lower staging and standard pancreaticoduodenectomy only. Therefore, the feasibility of portal vein resection should be evaluated in every potential candidate at risk. PMID- 27363996 TI - Bone microarchitecture deteriorations and a fragility fracture in a patient with beta and alpha heterozygous thalassemia: a case report. AB - To date there are few studies that have investigated bone mineral density (BMD) and markers of bone metabolism in patients with thalassemia minor form. None of the previous trials presented bone structure analysis in the patient populations. We present the case of a 24-year-old Turkish woman with heterozygous beta and alpha thalassemia who sustained a low-trauma fracture of the inferior pubic ramus. Despite normal markers of bone metabolism, the dual X-ray absorptiometry (DXA) showed decreased areal bone mineral density. Furthermore, severely reduced bone structure parameters and reduced volumetric bone mineral density was assessed by high-resolution peripheral quantitative computed tomography (HR pQCT). Due to these diagnostic findings at time of peak bone mass, an osteoanabolic therapy with teriparatide for 24 months was initiated. The findings concerning BMD and bone structure in this patient can be seen as caused by the beta and alpha thalassemia. PMID- 27363997 TI - Identification of two new keratinolytic proteases from a Bacillus pumilus strain using protein analysis and gene sequencing. AB - The Bacillus strain (CCUG 66887) has a high capacity to excrete keratinase with the ability to degrade both alpha- and beta keratin. In this study we aimed to show the characteristics of the keratinolytic protease and to identify its gene by using liquid chromatography-electrospray ionization tandem mass spectrometry methods (nanoHPLC-ESI-MS/MS) followed by Mascot data base search. The results showed that the enzyme in fact consists of two different keratinases, both with a molecular mass of 38 kDa. Further, DNA sequencing generated the open reading frame (ORF) of one of the genes (Ker1), and de novo genome sequencing identified the ORF of the second gene (Ker2). The two keratinase genes contain 1153 base pairs each and have a gene similarity of 67 %. In addition, the Bacillus strain was classified as Bacillus pumilus and its genes were annotated in the GeneBank at NCBI (accession: CP011109.1). Amino acid sequences alignment with known B. pumilus proteases indicated that the two keratinases of B. pumilus strain C4 are subtilisin-like serine proteases belonging to the Protease S8 family. Taken together, these result suggest the two keratinases as promising candidates for enzymatic processing of keratinous wastes in waste refinery. PMID- 27363998 TI - What does Brexit mean for doctors working in the UK? PMID- 27364000 TI - Recent Advances in Antischistosomal Drugs and Agents. AB - Schistosomiasis is a notable neglected tropical disease caused by trematodes that inflame mainly the intestines, bladder, and liver. Because of the unavailability of a schistosomiasis vaccine, control of the disease depends mainly on chemotherapy. Praziquantel (PZQ), which is active against all schistosome species and the recommended drug by the World Health Organization for schistosomiasis treatment at either the community or individual level, has become the exclusive drug because of its low cost and efficacy against the adult form of all schistosome species. In view of rapid re-infection following treatment and concern about the development of tolerance and/or resistance to praziquantel, there is an urgent need for research and development of novel drugs for the prevention and treatment of schistosomiasis. This comprehensive review shall attempt to briefly review the recent advances in the chemotherapy of schistosomiasis in the literature from 1990s to now, particularly focusing on the context of potential development of antischistosomal agents. Their antischistosomal properties, advantages, and disadvantages as well as structure activity relationships are reviewed in a simple manner. It shall be of interest for both the synthetic chemist as well as the pharmacologist. PMID- 27363999 TI - A next generation sequencing-based method to study the intra-host genetic diversity of norovirus in patients with acute and chronic infection. AB - BACKGROUND: Immunocompromised individuals with chronic norovirus (NoV) infection and elderly patients are hypothesized to be reservoirs where NoV might accumulate mutations and evolve into pandemic strains. Next generation sequencing (NGS) methods can monitor the intra-host diversity of NoV and its evolution but low abundance of viral RNA results in sub-optimal efficiency. In this study, we: 1) established a next generation sequencing-based method for NoV using bacterial rRNA depletion as a viral RNA enrichment strategy, and 2) measured the intra-host genetic diversity of NoV in specimens of patients with acute NoV infection (n = 4) and in longitudinal specimens of an immunocompromised patient with chronic NoV infection (n = 2). RESULTS: A single Illumina MiSeq dataset resulted in near full length genome sequences for 5 out of 6 multiplexed samples. Experimental depletion of bacterial rRNA in stool RNA provided up to 1.9 % of NoV reads. The intra-host viral population in patients with acute NoV infection was homogenous and no single nucleotide variants (SNVs) were detected. In contrast, the NoV population from the immunocompromised patient was highly diverse and accumulated SNVs over time (51 SNVs in the first sample and 122 SNVs in the second sample collected 4 months later). The percentages of SNVs causing non-synonymous mutations were 27.5 % and 20.5 % for the first and second samples, respectively. The majority of non-synonymous mutations occurred, in increasing order of frequency, in p22, the major capsid (VP1) and minor capsid (VP2) genes. CONCLUSIONS: The results provide data useful for the selection and improvement of NoV RNA enrichment strategies for NGS. Whole genome analysis using next generation sequencing confirmed that the within-host population of NoV in an immunocompromised individual with chronic NoV infection was more diverse compared to that in individuals with acute infection. We also observed an accumulation of non-synonymous mutations at the minor capsid gene that has not been reported in previous studies and might have a role in NoV adaptation. PMID- 27364002 TI - Comparing Social Anxiety Between Asian Americans and European Americans: An Examination of Measurement Invariance. AB - There have been over 30 studies and two meta-analyses comparing social anxiety between Asian Americans and European Americans. However, few have investigated the invariance of social anxiety measures that would make these comparisons appropriate. In the current study, we systematically examined psychometric properties and configural, metric, and scalar invariance of five social anxiety measures and four short forms that have been used more than once to compare Asian Americans ( n = 232) and European Americans ( n = 193). We found that four (i.e., SPS-6, SIAS-6, SPS, and SPAI-18) of the nine scales were scalar invariant, three scales (i.e., SIAS, SPAI, and B-FNES) only achieved configural invariance, and two scales (i.e., FNES and SADS) failed to achieve configural invariance. Latent mean comparisons based on the scalar invariant measures revealed higher social anxiety scores for Asian Americans than European Americans. The findings are discussed with regard to the issues and challenges when comparing social anxiety among different cultural and ethnic groups. PMID- 27364001 TI - Four-dimensional flow magnetic resonance imaging and ultrasound assessment of cerebrospinal venous flow in multiple sclerosis patients and controls. AB - A possibly causal relationship between multiple sclerosis and chronic cerebrospinal venous insufficiency has recently been hypothesized. Studies investigating chronic cerebrospinal venous insufficiency have reported conflicting results and few have employed multiple diagnostic imaging modalities across a large patient and control population. In this study, three complementary imaging modalities were used to investigate the chronic cerebrospinal venous insufficiency hypothesis in patients with multiple sclerosis and two age- and sex matched control groups: healthy volunteers and patients with other neurological diseases. Strictly blinded Doppler ultrasound according to the original chronic cerebrospinal venous insufficiency hypothesis; four-dimensional flow magnetic resonance imaging of venous flow in the head, neck, and chest; and contrast enhanced magnetic resonance venography for neck and chest venous luminography were acquired. An internal jugular vein stenosis evaluation was also performed across modalities. Percentage of subjects meeting ultrasound-based chronic cerebrospinal venous insufficiency criteria was small and similar between groups. In group-wise and pairwise testing, no four-dimensional flow magnetic resonance imaging variables were statistically significantly different, for any measurement location. In contrast-enhanced magnetic resonance venography of the internal jugular and azygos veins, no statistically significant differences were observed in stenosis scores between groups. These results represent compelling evidence against the chronic cerebrospinal venous insufficiency hypothesis in multiple sclerosis. PMID- 27364003 TI - Rates of Abnormally Low TOPF Word Reading Scores in Individuals Failing Versus Passing Performance Validity Testing. AB - The present study examined the impact of performance validity test (PVT) failure on the Test of Premorbid Functioning (TOPF) in a sample of 252 neuropsychological patients. Word reading performance differed significantly according to PVT failure status, and number of PVTs failed accounted for 7.4% of the variance in word reading performance, even after controlling for education. Furthermore, individuals failing >=2 PVTs were twice as likely as individuals passing all PVTs (33% vs. 16%) to have abnormally low obtained word reading scores relative to demographically predicted scores when using a normative base rate of 10% to define abnormality. When compared with standardization study clinical groups, those failing >=2 PVTs were twice as likely as patients with moderate to severe traumatic brain injury and as likely as patients with Alzheimer's dementia to obtain abnormally low TOPF word reading scores. Findings indicate that TOPF word reading based estimates of premorbid functioning should not be interpreted in individuals invalidating cognitive testing. PMID- 27364004 TI - Women's Attitudes Toward Intimate Partner Violence in Ethiopia: The Role of Social Norms in the Interview Context. AB - This study draws on a social norms framework to examine the influence of interview context-specifically the presence of other women and men-on women's reported attitudes toward intimate partner violence (IPV) in Ethiopia, where IPV rates are among the highest in the world. The sample (16,515 women, ages 15-49) was taken from Ethiopia's 2011 Demographic and Health Survey. Results showed the odds of women "justifying" IPV to be nearly twice as great when other women were present during the interview, and nearly half in the presence of men. Implications for more sensitive interview methodology are discussed. PMID- 27364005 TI - An Exploratory Case Study of a Sexual Assault Telephone Hotline: Training and Practice Implications. AB - Using archival data, this case study systematically examines telephone calls received by a regional sexual assault hotline in the Southeastern United States over a 5-year period. A stratified random sample ( n = 383) reveals that hotline staff require diversity and depth in knowledge and skills, demonstrated by the hotline's primary use as a crisis service, combined with notable use by long-term survivors. Findings include the utility of the hotline by survivors and community stakeholders, categories of assault, the time gap between incidents occurring and contacting the hotline, call severity and urgency, and services and referrals provided. Implications for training, practice, and future research are discussed. PMID- 27364006 TI - Application of a delta-6 desaturase with alpha-linolenic acid preference on eicosapentaenoic acid production in Mortierella alpina. AB - BACKGROUND: Delta-6 desaturase (FADS6) is a key bifunctional enzyme desaturating linoleic acid (LA) or alpha-linolenic acid (ALA) in the biosynthesis of polyunsaturated fatty acids (PUFAs). In previous work, we analyzed the substrate specificity of two FADS6 enzymes from Mortierella alpina ATCC 32222 (MaFADS6) and Micromonas pusilla CCMP1545 (MpFADS6), which showed preference for LA and ALA, respectively. We also clarified the PUFA profiles in M. alpina, where these lipids were synthesized mainly via the omega6 pathway and rarely via the omega3 pathway and as a result contained low ALA and eicosapentaenoic acid (EPA) levels. RESULT: To enhance EPA production in M. alpina by favoring the omega3 pathway, a plasmid harboring the MpFADS6 gene was constructed and overexpressed in a uracil auxotrophic strain of M. alpina using the Agrobacterium tumefaciens-mediated transformation (ATMT) method. Our results revealed that the EPA production reached 80.0 +/- 15.0 and 90.4 +/- 9.7 mg/L in MpFADS6 transformants grown at 28 and at 12 degrees C, respectively. To raise the level of ALA, free form fatty acid was used as exogenous substrate, which increased the EPA production up to 114.5 +/- 12.4 mg/L. To reduce the cost of EPA production in M. alpina, peony seed oil (PSO) and peony seed meal (PSM) were used as source of ALA, and EPA production was improved to 149.3 +/- 7.8 and 515.29 +/- 32.66 mg/L by supplementing with 0.1 % PSO and 50 g/L PSM, respectively. The EPA yield was further increased to 588.5 +/- 29.6 mg/L in a 5-L bioreactor, which resulted in a 26.2-fold increase compared to EPA production in wild-type M. alpina. In this work, we have significantly enhanced EPA production through overexpression of a FADS6 desaturase with preference for ALA, combined with supplementation of its substrate. CONCLUSION: An ALA-preferring FADS6 from M. pusilla CCMP1545 was applied to enhance EPA production in M. alpina. By exogenous addition of peony seed oil or peony seed meal, EPA production was further increased in flasks and fermenters. This research also highlights the value of peony seed meal which can be converted to a high value-added product containing EPA, and as a way to increase the EPA/AA ratio in M. alpina. PMID- 27364007 TI - Inositol pyrophosphates inhibit synaptotagmin-dependent exocytosis. AB - Inositol pyrophosphates such as 5-diphosphoinositol pentakisphosphate (5-IP7) are highly energetic inositol metabolites containing phosphoanhydride bonds. Although inositol pyrophosphates are known to regulate various biological events, including growth, survival, and metabolism, the molecular sites of 5-IP7 action in vesicle trafficking have remained largely elusive. We report here that elevated 5-IP7 levels, caused by overexpression of inositol hexakisphosphate (IP6) kinase 1 (IP6K1), suppressed depolarization-induced neurotransmitter release from PC12 cells. Conversely, IP6K1 depletion decreased intracellular 5 IP7 concentrations, leading to increased neurotransmitter release. Consistently, knockdown of IP6K1 in cultured hippocampal neurons augmented action potential driven synaptic vesicle exocytosis at synapses. Using a FRET-based in vitro vesicle fusion assay, we found that 5-IP7, but not 1-IP7, exhibited significantly higher inhibitory activity toward synaptic vesicle exocytosis than IP6 Synaptotagmin 1 (Syt1), a Ca(2+) sensor essential for synaptic membrane fusion, was identified as a molecular target of 5-IP7 Notably, 5-IP7 showed a 45-fold higher binding affinity for Syt1 compared with IP6 In addition, 5-IP7-dependent inhibition of synaptic vesicle fusion was abolished by increasing Ca(2+) levels. Thus, 5-IP7 appears to act through Syt1 binding to interfere with the fusogenic activity of Ca(2+) These findings reveal a role of 5-IP7 as a potent inhibitor of Syt1 in controlling the synaptic exocytotic pathway and expand our understanding of the signaling mechanisms of inositol pyrophosphates. PMID- 27364008 TI - Dimer interface of bovine cytochrome c oxidase is influenced by local posttranslational modifications and lipid binding. AB - Bovine cytochrome c oxidase is an integral membrane protein complex comprising 13 protein subunits and associated lipids. Dimerization of the complex has been proposed; however, definitive evidence for the dimer is lacking. We used advanced mass spectrometry methods to investigate the oligomeric state of cytochrome c oxidase and the potential role of lipids and posttranslational modifications in its subunit interfaces. Mass spectrometry of the intact protein complex revealed that both the monomer and the dimer are stabilized by large lipid entities. We identified these lipid species from the purified protein complex, thus implying that they interact specifically with the enzyme. We further identified phosphorylation and acetylation sites of cytochrome c oxidase, located in the peripheral subunits and in the dimer interface, respectively. Comparing our phosphorylation and acetylation sites with those found in previous studies of bovine, mouse, rat, and human cytochrome c oxidase, we found that whereas some acetylation sites within the dimer interface are conserved, suggesting a role for regulation and stabilization of the dimer, phosphorylation sites were less conserved and more transient. Our results therefore provide insights into the locations and interactions of lipids with acetylated residues within the dimer interface of this enzyme, and thereby contribute to a better understanding of its structure in the natural membrane. Moreover dimeric cytochrome c oxidase, comprising 20 transmembrane, six extramembrane subunits, and associated lipids, represents the largest integral membrane protein complex that has been transferred via electrospray intact into the gas phase of a mass spectrometer, representing a significant technological advance. PMID- 27364010 TI - Reply to Walker and Stickgold: Proposed boundary conditions on memory reconsolidation will require empirical verification. PMID- 27364009 TI - Epithelial Notch signaling regulates lung alveolar morphogenesis and airway epithelial integrity. AB - Abnormal enlargement of the alveolar spaces is a hallmark of conditions such as chronic obstructive pulmonary disease and bronchopulmonary dysplasia. Notch signaling is crucial for differentiation and regeneration and repair of the airway epithelium. However, how Notch influences the alveolar compartment and integrates this process with airway development remains little understood. Here we report a prominent role of Notch signaling in the epithelial-mesenchymal interactions that lead to alveolar formation in the developing lung. We found that alveolar type II cells are major sites of Notch2 activation and show by Notch2-specific epithelial deletion (Notch2(cNull)) a unique contribution of this receptor to alveologenesis. Epithelial Notch2 was required for type II cell induction of the PDGF-A ligand and subsequent paracrine activation of PDGF receptor-alpha signaling in alveolar myofibroblast progenitors. Moreover, Notch2 was crucial in maintaining the integrity of the epithelial and smooth muscle layers of the distal conducting airways. Our data suggest that epithelial Notch signaling regulates multiple aspects of postnatal development in the distal lung and may represent a potential target for intervention in pulmonary diseases. PMID- 27364011 TI - Understanding the boundary conditions of memory reconsolidation. PMID- 27364012 TI - Reply to Bistline and Blanford: Letter reaffirms conclusions and highlights flaws in previous research. PMID- 27364013 TI - More than one arrow in the quiver: Why "100% renewables" misses the mark. PMID- 27364014 TI - Early weaning impairs a social contagion of pain-related stretching behavior in mice. AB - Pain sensitivity in mice can be modulated through exposure to familiar individuals. This phenomenon is considered a form of emotional contagion, thought to be an evolutionary precursor of empathy in mammals. In particular, mother infant interactions early in life can considerably alter empathy development. Here, we demonstrated that pairs of mice that were simultaneously administered with a noxious stimulus (acetic acid) exhibited more pain-related behaviors than when one of the pair was treated with a noxious stimulus. However, these differences disappeared when mice were separated from the dam 1 week earlier than the typical weaning age. Even when mice were alone, when treated with acetic acid, early weaning decreased their pain response. These results suggested that the disruption of mother-infant bonding through early weaning impairs pain contagion and modulates sensitivity to pain. PMID- 27364015 TI - Porous silicon mass spectrometry as an alternative confirmatory assay for compliance testing of methadone. AB - Porous silicon based surface-assisted laser desorption ionization mass spectrometry (pSi SALDI-MS) is an analytical technique well suited for high throughput analysis of low molecular weight compounds from biological samples. A potential application of this technology is the compliance monitoring of opioid addiction programmes, where methadone is used as a pharmacological treatment for drugs such as heroin. Here, we present the detection and quantification of methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) from water and clinical samples (saliva, urine, and plasma) from opioid dependent participants using pSi SALDI-MS. A one-step solvent phase extraction using chloroform was developed for the detection of methadone from clinical samples for analysis by pSi SALDI-MS. Liquid chromatography-mass spectrometry (LC-MS) was used as a comparative technique for the quantification of methadone from clinical saliva and plasma samples. In all cases, we obtained a good correlation of pSi SALDI-MS and LC-MS results, suggesting that pSi SALDI-MS may be an alternative procedure for high-throughput screening and quantification for application in opioid compliance testing. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27364016 TI - Repeated Administrations of Cardiac Progenitor Cells Are Markedly More Effective Than a Single Administration: A New Paradigm in Cell Therapy. AB - RATIONALE: The effects of c-kit(POS) cardiac progenitor cells (CPCs, and adult cell therapy in general) on left ventricular (LV) function have been regarded as modest or inconsistent. OBJECTIVE: To determine whether 3 CPC infusions have greater efficacy than 1 infusion. METHODS AND RESULTS: Rats with a 30-day-old myocardial infarction received 1 or 3 CPC infusions into the LV cavity, 35 days apart. Compared with vehicle-treated rats, the single-dose group exhibited improved LV function after the first infusion (consisting of CPCs) but not after the second and third (vehicle). In contrast, in the multiple-dose group, regional and global LV function improved by a similar degree after each CPC infusion, resulting in greater cumulative effects. For example, the total increase in LV ejection fraction was approximately triple in the multiple-dose group versus the single-dose group (P<0.01). The multiple-dose group also exhibited more viable tissue and less scar, less collagen in the risk and noninfarcted regions, and greater myocyte density in the risk region. CONCLUSIONS: This is the first demonstration that repeated CPC administrations are markedly more effective than a single administration. The concept that the full effects of CPCs require repeated doses has significant implications for both preclinical and clinical studies; it suggests that the benefits of cell therapy may be underestimated or even overlooked if they are measured after a single dose, and that repeated administrations are necessary to evaluate the effectiveness of a cell product properly. In addition, we describe a new method that enables studies of repeated cell administrations in rodents. PMID- 27364017 TI - Lateral Membrane-Specific MAGUK CASK Down-Regulates NaV1.5 Channel in Cardiac Myocytes. AB - RATIONALE: Mechanisms underlying membrane protein localization are crucial in the proper function of cardiac myocytes. The main cardiac sodium channel, NaV1.5, carries the sodium current (INa) that provides a rapid depolarizing current during the upstroke of the action potential. Although enriched in the intercalated disc, NaV1.5 is present in different membrane domains in myocytes and interacts with several partners. OBJECTIVE: To test the hypothesis that the MAGUK (membrane-associated guanylate kinase) protein CASK (calcium/calmodulin dependent serine protein kinase) interacts with and regulates NaV1.5 in cardiac myocytes. METHODS AND RESULTS: Immunostaining experiments showed that CASK localizes at lateral membranes of cardiac myocytes, in association with dystrophin. Whole-cell patch clamp showed that CASK-silencing increases INa in vitro. In vivo CASK knockdown similarly increased INa recorded in freshly isolated myocytes. Pull-down experiments revealed that CASK directly interacts with the C-terminus of NaV1.5. CASK silencing reduces syntrophin expression without affecting NaV1.5 and dystrophin expression levels. Total Internal Reflection Fluorescence microscopy and biotinylation assays showed that CASK silencing increased the surface expression of NaV1.5 without changing mRNA levels. Quantification of NaV1.5 expression at the lateral membrane and intercalated disc revealed that the lateral membrane pool only was increased upon CASK silencing. The protein transport inhibitor brefeldin-A prevented INa increase in CASK-silenced myocytes. During atrial dilation/remodeling, CASK expression was reduced but its localization remained unchanged. CONCLUSION: This study constitutes the first description of an unconventional MAGUK protein, CASK, which directly interacts with NaV1.5 channel and controls its surface expression at the lateral membrane by regulating ion channel trafficking. PMID- 27364018 TI - Where Joy May Find Us. PMID- 27364019 TI - Commentary on "Where Joy May Find Us". PMID- 27364020 TI - House Staff Participation in Patient Safety Reporting: Identification of Predominant Barriers and Implementation of a Pilot Program. AB - OBJECTIVES: Patient safety event (PSE) reporting is a critical element for healthcare organizations that are striving for continuous quality improvement. Although resident physicians routinely provide the majority of direct patient care, the level of their participation in PSE reporting historically has been low. In addition, as part of the Accreditation Council for Graduate Medical Education's Next Accreditation System, the Clinical Learning Environment Review site visit assesses residents' engagement in PSE reporting at each accredited academic institution. The objective of this study was to understand the common barriers to PSE reporting and design an intervention to increase the number of PSE reports by resident physicians. METHODS: We surveyed 304 residents and fellows to assess attitudes toward the PSE reporting system and identify barriers to submitting online PSE reports. Based on this analysis of barriers, we piloted interventions with the internal medicine residency program and measured their effect on resident PSE reporting. RESULTS: Of the survey respondents, 58% had never submitted a PSE report. The most commonly identified barriers were too much time required to submit a report (38% of all respondents), lack of education on how or what to report (37%), lack of feedback or change after reporting (19%), and concern for repercussions or lack of anonymity (13%). Based on this analysis of barriers, we piloted interventions with the internal medicine residency program to educate residents about PSE reporting through a reminder message in their orientation e-mail, informational slides at the end of conferences that described what and how to report, a pocket card with reporting instructions, and leadership encouragement during walk rounds by chief medical residents and the program director. Compared with the 10 weeks before the start of the intervention, the number of PSE reports submitted by internal medicine residents more than doubled, from 16 to 37 reports (P < 0.01). This increase in resident PSE reporting was sustained for 20 weeks despite the interventions lasting only 8 weeks. CONCLUSIONS: A resident-driven intervention that fostered a culture of encouragement for PSE reporting through leadership support and targeted education increased the number of PSE reports submitted by internal medicine residents at our health system. Hospitals and health systems should seek to understand the common barriers to PSE reporting from this important group of direct patient care providers and administer structured educational programs to encourage their participation. PMID- 27364021 TI - Commentary on "House Staff Participation in Patient Safety Reporting: Identification of Predominant Barriers and Implementation of a Pilot Program". PMID- 27364023 TI - Commentary on "Examining Invasive Bedside Procedure Performance at an Academic Medical Center". PMID- 27364022 TI - Examining Invasive Bedside Procedure Performance at an Academic Medical Center. AB - OBJECTIVES: Explore the performance patterns of invasive bedside procedures at an academic medical center, evaluate whether patient characteristics predict referral, and examine procedure outcomes. METHODS: This was a prospective, observational, and retrospective chart review of adults admitted to a general medicine service who had a paracentesis, thoracentesis, or lumbar puncture between February 22, 2013 and February 21, 2014. RESULTS: Of a total of 399 procedures, 335 (84%) were referred to a service other than the primary team for completion. Patient characteristics did not predict referral status. Complication rates were low overall and did not differ, either by referral status or location of procedure. Model-based results showed a 41% increase in the average length of time until procedure completion for those referred to the hospital procedure service or radiology (7.9 vs 5.8 hours; P < 0.05) or done in radiology instead of at the bedside (9.0 vs 5.8 hours; P < 0.001). The average procedure cost increased 38% ($1489.70 vs $1023.30; P < 0.001) for referred procedures and 56% ($1625.77 vs $1150.98; P < 0.001) for radiology-performed procedures. CONCLUSIONS: Although referral often is the easier option, our study shows its shortcomings, specifically pertaining to cost and time until completion. Procedure performance remains an important skill for residents and hospitalists to learn and use as a part of patient care. PMID- 27364024 TI - Estimating the Net Career Income of a Geriatrician and a Nurse Practitioner: Still Want to Be a Doctor? AB - OBJECTIVES: With a continual shortage of geriatricians, adult-gerontology primary care nurse practitioners have assumed a greater role in the delivery of outpatient care for older adults. Given the long duration of physician training, the high cost of medical school, and the lower salaries compared with subspecialists, the financial advantage of a career as a geriatrician as opposed to a nurse practitioner is uncertain. This study compares the estimated career earnings of a geriatrician and an adult-gerontology primary care nurse practitioner. METHODS: We used a synthetic model of estimated net earnings during a 43-year career span for a 22-year old person embarking on a career as a geriatrician versus a career as an adult-gerontology primary care nurse practitioner. We estimated annual net income and net retirement savings using different annual compound rates and calculated the financial impact of forgiving medical student loans, shortening the duration of physician training, and reinstituting the practice pathway for geriatric medicine certification. RESULTS: Career net incomes for the geriatrician did not match the nurse practitioner until almost age 40. At 65 years of age, the difference between the geriatrician and nurse practitioner was 30.6%. A higher annual compound rate was associated with an even smaller percentage difference. Combining all three health policy interventions lowered the break-even age to 28 and more than doubled the difference in career earnings. CONCLUSIONS: Small estimated differences in net career earnings exist between geriatricians and adult-gerontology primary care nurse practitioners. Health policy interventions had a dramatic positive effect on geriatricians' lifetime net earnings in calculated estimates. PMID- 27364025 TI - Commentary on "Estimating the Net Career Income of a Geriatrician and a Nurse Practitioner: Still Want to Be a Doctor?". PMID- 27364026 TI - Pneumococcal Vaccine Eligibility Misconception. PMID- 27364027 TI - Authors' Response. PMID- 27364028 TI - Health Information Exchange in the ED: What Do ED Clinicians Think? AB - OBJECTIVES: Our regional health information exchange (HIE), known as Carolina eHealth Alliance (CeHA)-HIE, serves all major hospital systems in our region and is accessible to emergency department (ED) clinicians in those systems. We wanted to understand reasons for low CeHA-HIE utilization and explore options for improving it. METHODS: We implemented a 24-item user survey among ED clinician users of CeHA-HIE to investigate their perceptions of system usability and functionality, the quality of the information available through CeHA-HIE, the value of clinician time spent using CeHA-HIE, the ease of use of CeHA-HIE, and approaches for improving CeHA-HIE. RESULTS: Of the 231 ED clinicians surveyed, 51 responded, and among those, 48 reported having used CeHA-HIE and completed the survey. CONCLUSIONS: Results show most ED clinicians believed that CeHA-HIE was easy to use and added value to their work, but they also desired better integration of information available from CeHA-HIE into their system's electronic medical record. PMID- 27364029 TI - When Should ED Physicians Use an HIE? Predicting Presence of Patient Data in an HIE. AB - OBJECTIVES: Health information exchanges (HIEs) make possible the construction of databases to characterize patients as multisystem users (MSUs), those visiting emergency departments (EDs) of more than one hospital system within a region during a 1-year period. HIE data can inform an algorithm highlighting patients for whom information is more likely to be present in the HIE, leading to a higher yield HIE experience for ED clinicians and incentivizing their adoption of HIE. Our objective was to describe patient characteristics that determine which ED patients are likely to be MSUs and therefore have information in an HIE, thereby improving the efficacy of HIE use and increasing ED clinician perception of HIE benefit. METHODS: Data were extracted from a regional HIE involving four hospital systems (11 EDs) in the Charleston, South Carolina area. We used univariate and multivariable regression analyses to develop a predictive model for MSU status. RESULTS: Factors associated with MSUs included younger age groups, dual-payer insurance status, living in counties that are more rural, and one of at least six specific diagnoses: mental disorders; symptoms, signs, and ill-defined conditions; complications of pregnancy, childbirth, and puerperium; diseases of the musculoskeletal system; injury and poisoning; and diseases of the blood and blood-forming organs. For patients with multiple ED visits during 1 year, 43.8% of MSUs had >=4 visits, compared with 18.0% of non-MSUs (P < 0.0001). CONCLUSIONS: This predictive model accurately identified patients cared for at multiple hospital systems and can be used to increase the likelihood that time spent logging on to the HIE will be a value-added effort for emergency physicians. PMID- 27364031 TI - Erratum: Incorporating Patient Satisfaction Metrics in Assessing Multidisciplinary Breast Cancer Care Quality: Erratum. PMID- 27364030 TI - A Comprehensive View of Frequent Emergency Department Users Based on Data from a Regional HIE. AB - OBJECTIVES: A small but significant number of patients make frequent emergency department (ED) visits to multiple EDs within a region. We have a unique health information exchange (HIE) that includes every ED encounter in all hospital systems in our region. Using our HIE we were able to characterize all frequent ED users in our region, regardless of hospital visited or payer class. The objective of our study was to use data from an HIE to characterize patients in a region who are frequent ED users (FEDUs). METHODS: We constructed a database from a cohort of adult patients (18 years old or older) with information in a regional HIE for a 1-year period beginning in April 2012. Patients were defined as FEDUs (those who made four or more visits during the study period) and non-FEDUs (those who made fewer than four ED visits during the study period). Predictor variables included age, race, sex, payer class, county of residence, and International Classification of Diseases, Ninth Revision codes. Bivariate (chi(2)) and multivariate (logistic regression) analyses were performed to determine associations between predictor variables and the outcome of being a FEDU. RESULTS: The database contained 127,672 patients, 12,293 (9.6%) of whom were FEDUs. Logistic regression showed the following patient characteristics to be significantly associated with the outcome of being a FEDU: age 35 to 44 years; African American race; Medicaid, Medicare, and dual-pay payer class; and International Classification of Diseases, Ninth Revision codes 630 to 679 (complications of pregnancy, childbirth, and puerperium), 780 to 799 (ill-defined conditions), 280 to 289 (diseases of the blood), 290-319 (mental disorders), 680 to 709 (diseases of the skin and subcutaneous tissue), 710 to 739 (musculoskeletal and connective tissue disease), 460 to 519 (respiratory disease), and 520 to 579 (digestive disease). No significant differences were noted between men and women. CONCLUSIONS: Data from an HIE can be used to describe all of the patients within a region who are FEDUs, regardless of the hospital system they visited. This information can be used to focus care coordination efforts and link appropriate patients to a medical home. Future studies can be designed to learn the reasons why patients become FEDUs, and interventions can be developed to address deficiencies in health care that result in frequent ED visits. PMID- 27364032 TI - Poly(epsilon-caprolactone)-based substrates bearing pendant small chemical groups as a platform for systemic investigation of chondrogenesis. AB - OBJECTIVES: Physiochemical properties of biomaterials play critical roles in dictating types of cell behaviour. In this study, a series of poly(epsilon caprolactone) (PCL)-derived polymers bearing different small chemical groups was employed as a platform to evaluate chondrogenesis of different cell types. MATERIALS AND METHODS: Thin films were prepared by spin-coating PCL derivatives. Rabbit articular chondrocytes (rACs) and rabbit bone marrow-derived mesenchymal stem cells (rMSCs) were seeded on to the films, and cell adhesion, proliferation, extracellular matrix production and gene expression were evaluated. RESULTS: The presence of hydrophilic groups (-NH2 , -COOH, -OH and -C=O) promoted adhesion and proliferation of primary rACs and rMSCs. On these polymeric films, chondrogenesis of primary rACs depended on culture time. For passaged cells, re-differentiation was induced on these films by chondrogenic induction, but less for cells of passage 5 compared to passage 3. While films with hydrophilic groups favoured chondrocytic gene expression of both types of passaged cells, production of glycosaminoglycans (GAG) was similar for those of passage 3 on all films, and PCL CH3 film better supported GAG production for cells of passage 5. Under chondrogenic conditions, rMSCs were more efficient at GAG production on PCL and PCL-NH2 films. CONCLUSIONS: This study demonstrates that different cells displayed distinct responses to substrate surface chemistry, implying that cell biomaterial interactions can be developmental stage dependent. This provides a novel perspective for developing biomaterials for cartilage regeneration. PMID- 27364033 TI - Clinical management roles for junior doctors: an underused resource? PMID- 27364034 TI - Comment on Niemela and Colleagues (2016). PMID- 27364035 TI - The impact of infection by multidrug-resistant agents in patients with cirrhosis. A multicenter prospective study. AB - BACKGROUND & AIMS: Bacterial strains resistant to antibiotics are a serious clinical challenge. We assessed the antibiotic susceptibility of bacteria isolated from infections in patients with cirrhosis by a multicentre investigation. RESULTS: Three hundred and thirteen culture-positive infections (173 community acquired [CA] and 140 hospital acquired [HA]) were identified in 308 patients. Urinary tract infections, spontaneous bacterial peritonitis and bacteremias were the most frequent. Quinolone-resistant Gram-negative isolates were 48%, 44% were extended-spectrum beta-lactamase producers and 9% carbapenem resistant. In 83/313 culture-positive infections (27%), multidrug-resistant agents (MDRA) were isolated. This prevalence did not differ between CA and HA infections. MDRA were identified in 17 of 37 patients on quinolone prophylaxis, and in 46 of 166 not on prophylaxis (45% vs 27%; P<.03). In 287 cases an empiric antibiotic therapy was undertaken, in 37 (12.9%) this therapy failed. The in hospital mortality rate of this subset of patients was significantly higher compared to patients who received an effective broad(er)-spectrum therapy (P=.038). During a 3-month follow-up, 56/203 culture-positive patients (27.6%) died, 24/63 who have had MDRA-related infections (38%) and 32/140 who have had antibiotic-susceptible infections (22.8%) (P=.025). Multivariate analysis disclosed MDRA infection, age, hepatocellular carcinoma, bilirubin, international normalized ratio and the occurrence of portal hypertension-related complications independent predictors of death. CONCLUSIONS: Infection by MDRA is frequent in patients with cirrhosis and the prognosis is severe, especially in patients unresponsive to empiric antibiotic therapy. PMID- 27364036 TI - Influence of Polygenic Risk Scores on the Association Between Infections and Schizophrenia. AB - BACKGROUND: Several studies have suggested an important role of infections in the etiology of schizophrenia; however, shared genetic liability toward infections and schizophrenia could influence the association. We therefore investigated the possible effect of polygenic risk scores (PRSs) for schizophrenia on the association between infections and the risk of schizophrenia. METHODS: We conducted a nested case-control study on a Danish population-based sample born after 1981 comprising of 1692 cases diagnosed with schizophrenia between 1994 and 2008 and 1724 matched controls. All individuals were linked utilizing nationwide population-based registers with virtually complete registration of all hospital contacts for infections. PRSs were calculated using discovery effect size estimates weights from an independent meta-analysis (34,600 cases and 45,968 control individuals). RESULTS: A prior hospital contact with infection had occurred in 41% of the individuals with schizophrenia and increased the incidence rate ratio (IRR) of schizophrenia by 1.43 (95% confidence interval [CI] = 1.22 1.67). Adding PRS, which was robustly associated with schizophrenia (by an IRR of 1.46 [95% CI = 1.34-1.60] per standard deviation of the score), did not alter the association with infections and the increased risk of schizophrenia remained (IRR = 1.41; 95% CI = 1.20-1.66). Furthermore, there were no interactions between PRS and infections on the risk of developing schizophrenia (p = .554). Neither did PRS affect the risk of acquiring infections among patients with schizophrenia (odds ratio = 1.00; 95% CI = 0.89-1.12) nor among controls (odds ratio = 1.09; 95% CI: 0.96-1.24). CONCLUSIONS: PRS and a history of infections have independent effects on the risk for schizophrenia, and the common genetic risk measured by PRS did not account for the association with infection in this sample. PMID- 27364037 TI - Piezoelectricity and rotostriction through polar and non-polar coupled instabilities in bismuth-based piezoceramics. AB - Coupling of order parameters provides a means to tune functionality in advanced materials including multiferroics, superconductors, and ionic conductors. We demonstrate that the response of a frustrated ferroelectric state leads to coupling between order parameters under electric field depending on grain orientation. The strain of grains oriented along a specific crystallographic direction, , is caused by converse piezoelectricity originating from a ferrodistortive tetragonal phase. For oriented grains, the strain results from converse piezoelectricity and rotostriction, as indicated by an antiferrodistortive instability that promotes octahedral tilting in a rhombohedral phase. Both strain mechanisms combined lead to a colossal local strain of (2.4 +/- 0.1) % and indicate coupling between oxygen octahedral tilting and polarization, here termed "rotopolarization". These findings were confirmed with electromechanical experiments, in situ neutron diffraction, and in situ transmission electron microscopy in 0.75Bi1/2Na1/2TiO3-0.25SrTiO3. This work demonstrates that polar and non-polar instabilities can cooperate to provide colossal functional responses. PMID- 27364038 TI - Effect of Amalaki rasayana on DNA damage and repair in randomized aged human individuals. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Preparations from Phyllanthus emblica called Amalaki rasayana is used in the Indian traditional medicinal system of Ayurveda for healthy living in elderly. The biological effects and its mechanisms are not fully understood. Since the diminishing DNA repair is the hallmark of ageing, we tested the influence of Amalaki rasayana on recognized DNA repair activities in healthy aged individuals. METHODS: Amalaki rasayana was prepared fresh and healthy aged randomized human volunteers were administrated with either rasayana or placebo for 45 days strictly as per the traditional text. The DNA repair was analyzed in peripheral blood mononuclear cells before and after rasayana administration and after 45 days post-rasayana treatment regimen. UVC-induced DNA strand break repair (DSBR) based on extent of DNA unwinding by fluorometric analysis, nucleotide excision repair (NER) by flow cytometry and constitutive base excision repair (BER) by gap filling method were analyzed. RESULTS: Amalaki rasayana administration stably maintained/enhanced the DSBR in aged individuals. There were no adverse side effects. Further, subjects with different body mass index showed differential DNA strand break repair capacity. No change in unscheduled DNA synthesis during NER and BER was observed between the groups. CONCLUSION: Intake of Amalaki rasayana by aged individuals showed stable maintenance of DNA strand break repair without toxic effects. However, there was no change in nucleotide and base excision repair activities. Results warrant further studies on the effects of Amalaki rasayana on DSBR activities. PMID- 27364039 TI - Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: A review. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Nigella sativa (N. sativa) L. (Ranunculaceae), well known as black cumin, has been used as a herbal medicine that has a rich historical background. It has been traditionally and clinically used in the treatment of several diseases. Many reviews have investigated this valuable plant, but none of them focused on its clinical effects. Therefore, the aim of the present review is to provide a comprehensive report of clinical studies on N. sativa and some of its constituents. MATERIALS AND METHODS: Studies on the clinical effects of N. sativa and its main constituent, thymoquinone, which were published between 1979 and 2015, were searched using various databases. RESULTS AND DISCUSSION: During the last three decades, several in vivo and in vitro animal studies revealed the pharmacological properties of the plant, including its antioxidant, antibacterial, antiproliferative, proapoptotic, anti inflammatory, and antiepileptic properties, and its effect on improvement in atherogenesis, endothelial dysfunction, glucose metabolism, lipid profile dysfunction, and prevention of hippocampus pyramidal cell loss. In clinical studies, antimicrobial, antioxidant, anti-inflammatory, antitumor, and antidiabetic properties as well as therapeutic effects on metabolic syndrome, and gastrointestinal, neuronal, cardiovascular, respiratory, urinary, and reproductive disorders were found in N. sativa and its constituents. CONCLUSION: Extensive basic and clinical studies on N. sativa seed powder, oil, extracts (aqueous, ethanolic, and methanolic), and thymoquinone showed valuable therapeutic effects on different disorders with a wide range of safe doses. However, there were some confounding factors in the reviewed clinical trials, and a few of them presented data about the phytochemical composition of the plant. Therefore, a more standard clinical trial with N. sativa supplementation is needed for the plant to be used as an inexpensive potential biological adjuvant therapy. PMID- 27364040 TI - Obsessive compulsive personality disorder in Progressive Supranuclear Palsy, Multiple System Atrophy and Essential Tremor. AB - INTRODUCTION: aim of the study was to evaluate the presence of the Obsessive Compulsive Personality Disorder (OCPeD) in Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP) and Essential Tremor (ET) and in a group of healthy subjects. METHODS: patients affected by MSA, PSP and ET diagnosed according to currently accepted diagnostic criteria and a group of healthy controls were enrolled in the study. Patients with cognitive impairment were excluded from the study. The Structured Clinical Interview for Personality Disorders-II (SCID-II) has been performed to evaluate the presence of personality disorders (PeDs). The diagnosis of OCPeD was confirmed by a psychiatric interview. RESULTS: fifteen MSA patients (8 men and 7 women; aged 62.9 +/- 7.6 years), 14 PSP patients (8 men and 6 women; aged 69.8 +/- 4.4 years), 16 ET patients (10 men and 6 women; aged 70.4 +/- 6.4 years) and 20 healthy subjects (10 men and 10 women; aged 65.5 +/- 6.0 years) were enrolled. OCPeD was recorded in 5 (35.7%) PSP patients, 2 (13.3%) MSA patients, 2 (12.5%) ET patient and 2 (10%) controls. CONCLUSION: a low frequency of OCPeD, close to those recorded in healthy subjects, was recorded in both MSA and ET patients. Conversely an higher frequency of OCPeD, similar to PD was found among PSP patients, supporting the possibility of an impairment of common basal ganglia network possibly involving the orbito-frontal circuits. PMID- 27364041 TI - Cultural and Intellectual Openness Differentially Relate to Social Judgments of Potential Work Partners. AB - OBJECTIVE: This study investigates the differential functioning of cultural and intellectual openness (the two aspects of Openness to Experience) in relation to social cognitive processes by examining how they influence people's perceptions and interpretations of social information when deciding to initiate working relationships. METHOD: Using a policy-capturing design, 681 adult participants were asked to rate their similarity to and preference to work with potential work partners characterized by varying nationalities and levels of work-related competence. Multilevel moderated mediation was conducted to simultaneously evaluate whether the indirect effects of potential work partners' characteristics (i.e., nationalities and levels of work-related competence) on work partner preference through perceived similarity were moderated by cultural and intellectual openness. RESULTS: Perceived similarity mediated the relationships between work partner nationality and work-related competence and participants' work partner preferences. Furthermore, the negative indirect effect of work partner nationality on work partner preference via perceived similarity was attenuated by cultural openness, and the positive indirect effect of work partner work-related competence on work partner preference via perceived similarity was strengthened by intellectual openness. CONCLUSIONS: Cultural and intellectual openness may have distinct functions that influence how people perceive, evaluate, and appreciate social information when making social judgments. PMID- 27364042 TI - Phenolic compounds and biological effects of edible Rumex scutatus and Pseudosempervivum sempervivum: potential sources of natural agents with health benefits. AB - The present study outlines a chemical characterization and further effects beneficial to health of edible Rumex scutatus and Pseudosempervivum sempervivum, in addition to presenting the antioxidant, enzyme inhibitory effects and antimicrobial properties of different extracts. The phenolic compounds composition of the extracts was assessed by RP-HPLC-DAD, outlining benzoic acid and rutin as major constituents in P. sempervivum and rutin and hesperidin in R. scutatus. Moreover, further biological effects were tested on key enzymes involved in diabetes mellitus, Alzheimer's disease and skin melanogenesis revealing an important tyrosinase inhibitory effect of Pseudosempervivum water extract. Moreover, both species possessed antimicrobial properties towards bacteria and fungi relevant to public health. Accordingly, we find that R. scutatus and P. sempervivum can be considered as novel functional foods because they are rich sources of biologically active compounds that provide health benefits. PMID- 27364044 TI - Finally, a Drug Proves to Be Effective Against Vasovagal Syncope!: But Not in All Patients. PMID- 27364043 TI - Fludrocortisone for the Prevention of Vasovagal Syncope: A Randomized, Placebo Controlled Trial. AB - BACKGROUND: There is limited evidence whether being on fludrocortisone prevents vasovagal syncope. OBJECTIVES: The authors sought to determine whether treatment with fludrocortisone reduces the proportion of patients with recurrent vasovagal syncope by at least 40%, representing a pre-specified minimal clinically important relative risk reduction. METHODS: The multicenter POST 2 (Prevention of Syncope Trial 2) was a randomized, placebo-controlled, double-blind trial that assessed the effects of fludrocortisone in vasovagal syncope over a 1-year treatment period. All patients had >2 syncopal spells and a Calgary Syncope Symptom Score >-3. Patients received either fludrocortisone or matching placebo at highest tolerated doses from 0.05 mg to 0.2 mg daily. The main outcome measure was the first recurrence of syncope. RESULTS: The authors randomized 210 patients (71% female, median age 30 years) with a median 15 syncopal spells over a median of 9 years equally to fludrocortisone or placebo. Of these, 96 patients had >=1 syncope recurrences, and only 14 patients were lost to follow-up before syncope recurrence. There was a marginally nonsignificant reduction in syncope in the fludrocortisone group (hazard ratio [HR]: 0.69: 95% confidence interval [CI]: 0.46 to 1.03; p = 0.069). In a multivariable model, fludrocortisone significantly reduced the likelihood of syncope (HR: 0.63; 95% CI: 0.42 to 0.94; p = 0.024). When the analysis was restricted to outcomes after 2 weeks of dose stabilization, there was a significant benefit due to fludrocortisone (HR: 0.51; 95% CI: 0.28 to 0.89; p = 0.019). CONCLUSIONS: The study did not meet its primary objective of demonstrating that fludrocortisone reduced the likelihood of vasovagal syncope by the specified risk reduction of 40%. The study demonstrated a significant effect after dose stabilization, and there were significant findings in post hoc multivariable and on-treatment analyses. (A randomised clinical trial of fludrocortisone for the prevention of vasovagal syncope; ISRCTN51802652; Prevention of Syncope Trial 2 [POST 2]; NCT00118482). PMID- 27364045 TI - Cardiac Amyloid Load: A Prognostic and Predictive Biomarker in Patients With Light-Chain Amyloidosis. AB - BACKGROUND: Cardiac amyloid load has not been analyzed for its effect on mortality in patients with amyloid light-chain (AL) cardiac amyloidosis. OBJECTIVES: This study retrospectively compared histological amyloid load with common clinical predictors of mortality. METHODS: This study assessed 216 patients with histologically confirmed cardiac amyloidosis at a single center with electrocardiography, echocardiography, and laboratory testing. RESULTS: AL amyloid deposits were usually distributed in a reticular/pericellular pattern, whereas transthyretin amyloid (ATTR) more commonly showed patchy deposits. Median amyloid load was 30.5%; no amyloid load was above 70%. During follow-up (median 19.1 months), 112 patients died. Chemotherapy had a significant effect on overall survival in AL amyloidosis (16.2 months vs. 1.4 months; p = 0.003). Patients with <20% AL amyloid load who responded to chemotherapy showed significantly better survival than nonresponders. According to univariate analysis, predictors of survival in AL amyloidosis included sex, Karnofsky index, New York Heart Association (NYHA) functional class, diastolic blood pressure, estimated glomerular filtration rate, N-terminal pro-B-type natriuretic peptide, mineralocorticoid receptor antagonists, low voltage, ineligibility for chemotherapy, response to chemotherapy, and amyloid load. Independent predictors of mortality by multivariate analysis included NYHA functional class (III vs. II), estimated glomerular filtration rate, responders to chemotherapy, and amyloid load. In ATTR amyloidosis, survival correlated with NYHA functional class, diastolic blood pressure, and use of diuretic agents. Following Cox regression analysis, NYHA functional class (III vs. II; p < 0.05) remained the only independent predictor of patient survival in ATTR amyloidosis. CONCLUSIONS: Early identification of subjects with AL amyloid is essential given that in late stage disease with extensive amyloid load, our data suggested that outcomes are not affected by administration of chemotherapy. PMID- 27364046 TI - Amyloid Cardiomyopathy. PMID- 27364047 TI - Long-Term Mortality After Coronary Revascularization in Nondiabetic Patients With Multivessel Disease. AB - BACKGROUND: In diabetic patients with multivessel coronary artery disease (CAD), the survival difference between coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) favors CABG. However, there are few data on the mortality difference between the 2 strategies in nondiabetic patients. OBJECTIVES: This study performed a patient-level meta-analysis to compare the effect of CABG versus PCI with drug-eluting stents on long-term mortality in 1,275 nondiabetic patients with multivessel CAD. METHODS: Individual patient data from the SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) and the BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease) trials were pooled. The primary outcome was death from any cause. RESULTS: The median follow-up time was 61 months (interquartile range: 50 months to 62 months). The risk of death from any cause was significantly lower in the CABG group than in the PCI group (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.43 to 0.98; p = 0.039). A similar finding was observed for the risk of death from cardiac causes. The superiority of CABG over PCI was consistent across the major clinical subgroups. Likewise, the rate of myocardial infarction was remarkably lower after CABG than after PCI (HR: 0.40; 95% CI: 0.24 to 0.65; p < 0.001). However, the rate of stroke was not different between the 2 groups (HR: 1.13; 95% CI: 0.59 to 2.17; p = 0.714). The need for repeat revascularization was significantly lower in the CABG group than in the PCI group (HR: 0.55; 95% CI: 0.40 to 0.75; p < 0.001). CONCLUSIONS: CABG, as compared with PCI with drug-eluting stents, significantly reduced the long-term risk of mortality in nondiabetic patients with multivessel CAD. PMID- 27364048 TI - Multivessel CAD in Nondiabetic Patients: To Operate or to Dilate? PMID- 27364050 TI - Erythropoietin for Out-of-Hospital Cardiac Arrest: Growing Together or Apart? PMID- 27364049 TI - Early High-Dose Erythropoietin Therapy After Out-of-Hospital Cardiac Arrest: A Multicenter, Randomized Controlled Trial. AB - BACKGROUND: Preliminary data suggested a clinical benefit in treating out-of hospital cardiac arrest (OHCA) patients with a high dose of erythropoietin (Epo) analogs. OBJECTIVES: The authors aimed to evaluate the efficacy of epoetin alfa treatment on the outcome of OHCA patients in a phase 3 trial. METHODS: The authors performed a multicenter, single-blind, randomized controlled trial. Patients still comatose after a witnessed OHCA of presumed cardiac origin were eligible. In the intervention group, patients received 5 intravenous injections spaced 12 h apart during the first 48 h (40,000 units each, resulting in a maximal dose of 200,000 total units), started as soon as possible after resuscitation. In the control group, patients received standard care without Epo. The main endpoint was the proportion of patients in each group reaching level 1 on the Cerebral Performance Category (CPC) scale (survival with no or minor neurological sequelae) at day 60. Secondary endpoints included all-cause mortality rate, distribution of patients in CPC levels at different time points, and side effects. RESULTS: In total, 476 patients were included in the primary analysis. Baseline characteristics were similar in the 2 groups. At day 60, 32.4% of patients (76 of 234) in the intervention group reached a CPC 1 level, as compared with 32.1% of patients (78 of 242) in the control group (odds ratio: 1.01; 95% confidence interval: 0.68 to 1.48). The mortality rate and proportion of patients in each CPC level did not differ at any time points. Serious adverse events were more frequent in Epo-treated patients as compared with controls (22.6% vs. 14.9%; p = 0.03), particularly thrombotic complications (12.4% vs. 5.8%; p = 0.01). CONCLUSIONS: In patients resuscitated from an OHCA of presumed cardiac cause, early administration of erythropoietin plus standard therapy did not confer a benefit, and was associated with a higher complication rate. (High Dose of Erythropoietin Analogue After Cardiac Arrest [Epo-ACR-02]; NCT00999583). PMID- 27364052 TI - An MR Spectroscopy-Based Approach to Lean Versus Obese Diabetic Patients. PMID- 27364053 TI - The Genesis, Maturation, and Future of Critical Care Cardiology. AB - The cardiac intensive care unit (CICU) has changed considerably over time and now serves a unique patient population with a high burden of cardiovascular and noncardiovascular critical illness. Patient complexity and technological evolutions in the CICU have catalyzed the development of critical care cardiology, a fledgling discipline that combines specialization in cardiovascular diseases with knowledge and experience in critical care medicine. Numerous uncertainties and challenges threaten to stymie the growth of this field. A multidisciplinary dialogue focused on the best care design for the CICU patient is needed as we consider alternative approaches to clinical training, staffing, and investigation in this rapidly evolving arena. PMID- 27364054 TI - Allograft Vasculopathy: The Achilles' Heel of Heart Transplantation. AB - Cardiac allograft vasculopathy (CAV) remains the Achilles' heel of long-term survival after heart transplantation. Almost one-third of patients develop CAV by 5 years post-transplant and 1 in 8 deaths beyond a year are due to CAV. Abnormal vascular fibroproliferation in CAV occurs as a result of coronary endothelial inflammation, injury, and dysfunction triggered by immune and nonimmune insults. Surveillance methods for CAV have significant limitations, particularly for detecting early disease. Areas of investigation include myocardial and coronary blood flow quantification, and intracoronary imaging to detect early changes in the vessel wall and high-risk plaques. Treatment approaches continue to evolve, but prevention remains the focus. Newer mammalian target of rapamycin inhibitors can significantly delay the progression of CAV; however, their optimal use remains to be established. Further investigation is needed to understand the complex pathophysiology of CAV, improve surveillance techniques, and develop therapies to prevent and slow disease progression. PMID- 27364051 TI - Ectopic and Visceral Fat Deposition in Lean and Obese Patients With Type 2 Diabetes. AB - BACKGROUND: Type 2 diabetes (T2D) and obesity are associated with nonalcoholic fatty liver disease, cardiomyopathy, and cardiovascular mortality. Both show stronger links between ectopic and visceral fat deposition, and an increased cardiometabolic risk compared with subcutaneous fat. OBJECTIVES: This study investigated whether lean patients (Ln) with T2D exhibit increased ectopic and visceral fat deposition and whether these are linked to cardiac and hepatic changes. METHODS: Twenty-seven obese patients (Ob) with T2D, 15 Ln-T2D, and 12 normal-weight control subjects were studied. Subjects underwent cardiac computed tomography, cardiac magnetic resonance imaging (MRI), proton and phosphorus MR spectroscopy, and multiparametric liver MR, including hepatic proton MRS, T1- and T2*-mapping yielding "iron-corrected T1" [cT1]. RESULTS: Diabetes, with or without obesity, was associated with increased myocardial triglyceride content (p = 0.01), increased hepatic triglyceride content (p = 0.04), and impaired myocardial energetics (p = 0.04). Although cardiac structural changes, steatosis, and energetics were similar between the T2D groups, epicardial fat (p = 0.04), hepatic triglyceride (p = 0.01), and insulin resistance (p = 0.03) were higher in Ob-T2D. Epicardial fat, hepatic triglyceride, and insulin resistance correlated negatively with systolic strain and diastolic strain rates, which were only significantly impaired in Ob-T2D (p < 0.001 and p = 0.006, respectively). Fibroinflammatory liver disease (elevated cT1) was only evident in Ob-T2D patients. cT1 correlated with hepatic and epicardial fat (p < 0.001 and p = 0.01, respectively). CONCLUSIONS: Irrespective of body mass index, diabetes is related to significant abnormalities in cardiac structure, energetics, and cardiac and hepatic steatosis. Obese patients with T2D show a greater propensity for ectopic and visceral fat deposition. PMID- 27364055 TI - Second Anniversary as JACC's Editor-in-Chief: Maintaining Focus Through Simplicity and Insightfulness, With a Look Toward Advocacy. PMID- 27364056 TI - Mechanism of Symptomatic Improvement After Percutaneous Therapy for Secondary Mitral Regurgitation: Resting and Exercise Hemodynamics. PMID- 27364057 TI - Dabigatran Versus Warfarin in Relation to Renal Function in Patients With Atrial Fibrillation. PMID- 27364058 TI - Pulse Pressure and Cardiovascular Death. PMID- 27364059 TI - Reply: Pulse Pressure and Cardiovascular Death. PMID- 27364060 TI - Sex-Specific Data for the Subcutaneous Implantable Cardioverter-Defibrillator. PMID- 27364061 TI - Factors Affecting Platelet Reactivity and Cardiovascular Outcome in CAD Patients Treated With P2Y12 Receptor Inhibitors. PMID- 27364062 TI - Correction. PMID- 27364063 TI - Correction. PMID- 27364080 TI - Understanding the costs of flexible ureteroscopy. AB - Ureteroscopy (URS) is the first line treatment for the majority of symptomatic renal and ureteral stones. This review summarizes the current literature on the costs associated with URS. A high initial investment is required for scope acquisition. Once purchased, maintenance and repair costs continue to accrue. Durability of the scopes is an important consideration as more durable scopes will remain functional for longer and thus have lower overall repair costs. Currently available, newer generation scopes appear highly durable compared to their predecessors. Ancillary equipment, mostly disposable items represent the highest per procedure cost of URS. Despite these costs, URS remains highly profitable. However, it is also efficacious demonstrating superior cost effectiveness with higher stone free rates at a lower cost relative to shock wave lithotripsy. PMID- 27364082 TI - Analysis of the synonymous codon usage bias in recently emerged enterovirus D68 strains. AB - Understanding the codon usage pattern of a pathogen and relationship between pathogen and host's codon usage patterns has fundamental and applied interests. Enterovirus D68 (EV-D68) is an emerging pathogen with a potentially high public health significance. In the present study, the synonymous codon usage bias of 27 recently emerged, and historical EV-D68 strains was analyzed. In contrast to previously studied enteroviruses (enterovirus 71 and poliovirus), EV-D68 and human host have a high discrepancy between favored codons. Analysis of viral synonymous codon usage bias metrics, viral nucleotide/dinucleotide compositional parameters, and viral protein properties showed that mutational pressure is more involved in shaping the synonymous codon usage bias of EV-D68 than translation selection. Computation of codon adaptation indices allowed to estimate expression potential of the EV-D68 genome in several commonly used laboratory animals. This approach requires experimental validation and may provide an auxiliary tool for the rational selection of laboratory animals to model emerging viral diseases. Enterovirus D68 genome compositional and codon usage data can be useful for further pathogenesis, animal model, and vaccine design studies. PMID- 27364081 TI - Antennal transcriptome and differential expression of olfactory genes in the yellow peach moth, Conogethes punctiferalis (Lepidoptera: Crambidae). AB - The yellow peach moth (YPM), Conogethes punctiferalis (Guenee), is a multivoltine insect pest of crops and fruits. Antennal-expressed receptors are important for insects to detect olfactory cues for host finding, mate attraction and oviposition site selection. However, few olfactory related genes were reported in YPM until now. In the present study, we sequenced and characterized the antennal transcriptomes of male and female YPM. In total, 15 putative odorant binding proteins (OBPs), 46 putative odorant receptors (ORs) and 7 putative ionotropic receptors (IRs) were annotated and identified as olfactory-related genes of C. punctiferalis. Further analysis of RT-qPCR revealed that all these olfactory genes are primarily or uniquely expressed in male and female antennae. Among which, 3 OBPs (OBP4, OBP8 and PBP2) and 4 ORs (OR22, OR26, OR44 and OR46) were specially expressed in male antennae, whereas 4 ORs (OR5, OR16, OR25 and OR42) were primarily expressed in female antennae. The predicted protein sequences were compared with homologs in other lepidopteran species and model insects, which showed high sequence homologies between C. punctiferalis and O. furnacalis. Our work allows for further functional studies of pheromone and general odorant detection genes, which might be meaningful targets for pest management. PMID- 27364083 TI - Differentially expressed genes of Chenopodium amaranticolor in response to cymbidium mosaic virus infection. AB - Cymbidium mosaic virus (CymMV)-induced expressed sequence tag (EST) clones from Chenopodium amaranticolor were identified. CymMV was mechanically inoculated onto C. amaranticolor, and local lesion symptoms were observed. Inoculated leaves were collected on serial days post inoculation (dpi) to identify activated or suppressed genes. mRNA isolation and suppression subtractive hybridization (SSH) were then performed to identify differentially expressed genes related to the local lesion response. Fifty-three ESTs, including genes related to defense and stress responses (e.g., lipoxygenase, jasmonate-induced protein, and heat shock protein), were generated. In addition, a large proportion of the ESTs were found to be involved in photosynthesis, as determined by their functional categories. Expression levels of several EST genes were observed using quantitative real-time reverse transcription-polymerase chain reaction, and the evaluated genes showed varying levels of expression during the experimental period. In this study, differentially expressed sequences via SSH were identified from CymMV-infected C. amaranticolor, and profiling and annotation were carried out to determine the expression pattern of CymMV and its interaction with C. amaranticolor. PMID- 27364084 TI - Factors affecting the success of a large embryo transfer program in Holstein cattle in a commercial herd in the southeast region of the United States. AB - The objectives of this study were to evaluate factors affecting in vivo embryo production and pregnancy per embryo transfer (P/ET) in Holstein cattle in the southeast region of the United States. Data from a total of 516 embryo collections and 10,297 ETs performed from 2011 to 2014 were available. For embryo production, the effects of donor parity (nulliparous [N], primiparous [P], multiparous [M]), average temperature-humidity index (THI) at embryo collection, days in milk at embryo collection, occurrence of calving problems, and occurrence of metritis postpartum were evaluated. For P/ET, the effects of donor parity (N or parous), recipient parity (N, P, and M), embryo type (fresh, frozen, IVF, and IVF-frozen), embryo developmental stage (4-7), embryo quality (1-3), recipient estrous cycle day at ET (6-9), average THI at ET, days in milk at ET, milk yield at ET, occurrence of calving problems (abortion, dystocia, twins, fetal death, or retained placenta), and occurrence of metritis postpartum were evaluated. Pregnancy was diagnosed at 41 +/- 3 days of gestation. Continuous and binary data were analyzed using the MIXED and GLIMMIX procedures of SAS, respectively. Parity affected embryo production; M had greater number and percentage of unfertilized embryos and lesser percentage of viable embryos than P and N. Recipient parity, embryo type, embryo stage, embryo quality, estrous cycle day at ET, and THI at ET affected P/ET. There was an interaction between recipient parity and THI at ET. P/ET was greater for N than P and greater for P than M, greater for fresh embryos than others, greater for stage 7 than others, greater for quality 1 than 2 and greater for quality 2 than 3, and greater for ET on estrous cycle Day 7 and 8 than 6. P/ET was decreased for THI >=80 in N and THI >=72 in P and M. Calving problems and metritis also affected P/ET in P and M and was lesser for cows that had calving problems and metritis. In conclusion, embryo production was affected by donor parity, and P/ET was affected by embryo type, embryo stage, embryo quality, recipient estrous cycle day at ET, THI, calving problems, and metritis. PMID- 27364086 TI - Spontaneous formation of three-dimensionally ordered Bi-rich nanostructures within GaAs1-x Bi x /GaAs quantum wells. AB - In this work, we report on the spontaneous formation of ordered arrays of nanometer-sized Bi-rich structures due to lateral composition modulations in Ga(As,Bi)/GaAs quantum wells grown by molecular beam epitaxy. The overall microstructure and chemical distribution is investigated using transmission electron microscopy. The information is complemented by synchrotron x-ray grazing incidence diffraction, which provides insight into the in-plane arrangement. Due to the vertical inheritance of the lateral modulation, the Bi-rich nanostructures eventually shape into a three-dimensional assembly. Whereas the Bi-rich nanostructures are created via two-dimensional phase separation at the growing surface, our results suggest that the process is assisted by Bi segregation which is demonstrated to be strong and more complex than expected, implying both lateral and vertical (surface segregation) mass transport. As demonstrated here, the inherent thermodynamic miscibility gap of Ga(As,Bi) alloys can be exploited to create highly uniform Bi-rich units embedded in a quantum confinement structure. PMID- 27364085 TI - Rotational thyrotracheopexy after cricoidectomy for low-grade laryngeal chrondrosarcoma. AB - OBJECTIVES: The complex laryngeal functions are fundamentally defined by the cricoid cartilage. Thus, lesions requiring subtotal or total resection of the cricoid cartilage commonly warrant total laryngectomy. However, from an oncological perspective, the resection of the cricoid cartilage would be an optimal solution in these cases. The poor functional results of the few reported cases of total and subtotal cricoidectomy with different reconstruction techniques confirm the need for new approaches to reconstruct the infrastructure of the larynx post cricoidectomy. STUDY DESIGN: Retrospective case series review. METHODS: Four consecutive patients with low-grade chondrosarcoma were treated by cricoidectomy with rotational thyrotracheopexy reconstruction to enable the functional creation of a complete cartilaginous ring that can substitute the functions of the cricoid cartilage. The glottic structures were stabilized with endoscopic arytenoid abduction lateropexy. Patients were evaluated with objective and subjective function tests. RESULTS: Tumor-free margins were proven; patients were successfully decannulated within 3 weeks. Voice outcomes were adequate for social conversation in all cases. Oral feeding was possible in three patients. CONCLUSION: Total and subtotal cricoidectomy can be a surgical option to avoid total laryngectomy in cases of large chondrosarcomas destroying the cricoid cartilage. The thyrotracheopexy rotational advancement technique enables the effective reconstruction of the structural deficit of the resected cricoid cartilage in cases of total and subtotal cricoidectomy. An adequate airway for breathing, swallowing, and voice production can be reconstructed with good oncological control. In cases where the pharynx is not involved, good swallowing function can also be achieved. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1109-1115, 2017. PMID- 27364087 TI - Evaluation of the effect of an angiotensin-converting enzyme inhibitor, alacepril, on drug-induced renin-angiotensin-aldosterone system activation in normal dogs. AB - INTRODUCTION: To determine if alacepril, an angiotensin-converting enzyme inhibitor, has a long duration of action for inhibition of drug-induced renin angiotensin-aldosterone system (RAAS) activation in normal dogs. ANIMALS: Five healthy laboratory dogs were used in this study. MATERIALS AND METHODS: Each dog received amlodipine (0.5 mg/kg, q12h, p.o.) for 14 days, followed by amlodipine (0.5 mg/kg, q12h, p.o.) and alacepril (1.5 mg/kg, q12h, p.o.) for 56 days. Blood pressure (systolic blood pressure [SBP]; mean blood pressure; and diastolic blood pressure), heart rate, and urinary aldosterone-to-creatinine ratio (UAld:Cre), as an indicator of RAAS activation, were measured on days -14, 0 (baseline [BL]), 1, 7, 14, 28, and 56. RESULTS: SBP decreased by 10% (p=0.08), and UAld:Cre increased significantly (p=0.04) relative to the BL level after administration of amlodipine. SBP increased after 14 days of alacepril administration relative to BL (p=0.97), and statistically significant increase was first observed on day 28 (p=0.02). Heart rate significantly decreased after alacepril administration on days 14, 28, and 56 (p=0.02). UAld:Cre significantly decreased after alacepril administration on days 14 and 28 (p<=0.03) relative to the BL level but increased on day 56 such that the difference was no longer significant (p=0.32). DISCUSSION: These incomplete and temporary pharmacological blockade of RAAS activation by alacepril suggest that aldosterone breakthrough may have occurred. CONCLUSIONS: Alacepril inhibited activation of RAAS in the short term but is not expected to have a long duration of action. PMID- 27364088 TI - Successful treatment of mitral valve endocarditis in a dog associated with 'Actinomyces canis-like' infection. AB - Infective endocarditis, an inflammation of the endocardial surface due to invasion by an infectious agent, is more common in middle sized to large breed dogs. We herein report a case of mitral valve endocarditis in a 9-year-old male castrated Weimaraner caused by an Actinomyces canis-like bacterium, not previously reported in association with infection in dogs. PMID- 27364089 TI - Automated otolith image classification with multiple views: an evaluation on Sciaenidae. AB - Combined multiple 2D views (proximal, anterior and ventral aspects) of the sagittal otolith are proposed here as a method to capture shape information for fish classification. Classification performance of single view compared with combined 2D views show improved classification accuracy of the latter, for nine species of Sciaenidae. The effects of shape description methods (shape indices, Procrustes analysis and elliptical Fourier analysis) on classification performance were evaluated. Procrustes analysis and elliptical Fourier analysis perform better than shape indices when single view is considered, but all perform equally well with combined views. A generic content-based image retrieval (CBIR) system that ranks dissimilarity (Procrustes distance) of otolith images was built to search query images without the need for detailed information of side (left or right), aspect (proximal or distal) and direction (positive or negative) of the otolith. Methods for the development of this automated classification system are discussed. PMID- 27364091 TI - Editorial Comment for Zhong et al. PMID- 27364090 TI - Electrical burns in times of economic crisis: A new epidemiologic profile. AB - Electrical injuries and especially those of high voltage still remain a source of high morbidity. Over the past few years, a change in the epidemiologic profile of these lesions was noticed at the Vall d'Hebron University Hospital Burn Unit, corresponding to an increase in cases out of the legal framework. It is our aim to describe this particular subset, to determine the extent of their injuries and to understand the reason for their increased incidence. We think this was favoured by the rise in the unemployment rate, along with higher copper prices. PMID- 27364092 TI - Phenotypic variability of R117H-CFTR expression within monozygotic twins. AB - Whilst cystic fibrosis is a monogenic condition, variation in phenotype exists for the same CFTR genotype, which is influenced by multiple genetic and non genetic (environmental) factors. The R117H-CFTR mutation has variability directly relating to in cis poly-thymidine alleles, producing a differing spectrum of disease. This paper provides evidence of extreme phenotype variability - including fertility status - in the context of male monogenetic twins, discussing mechanisms and highlighting the diagnostic and treatment challenges. PMID- 27364093 TI - Metabolomics reveals differences between three daidzein metabolizing phenotypes in adults with cardiometabolic risk factors. AB - SCOPE: The soy isoflavone, daidzein, is metabolized by gut microbiota to O desmethylangolensin (ODMA) and/or equol. Producing equol is postulated as a contributing factor for the beneficial effects of soy. METHODS AND RESULTS: This randomized, controlled, cross-over design used an untargeted metabolomic approach to assess the metabolic profile of different daidzein metabolizers. Adults (n = 17) with cardiometabolic risk factors received soy nuts or control food for 4 weeks, separated by a 2-week washout. No significant differences were detected pre- and postintervention and between interventions. Examination of the ability to metabolize daidzein revealed three groups: ODMA only producers (n = 4), equol + ODMA producers (n = 8), and nonproducers (n = 5). Analysis of the serum metabolome revealed nonproducers could be distinguished from ODMA-only and equol + ODMA producers. Differences between these phenotypes were related to obesity and metabolic risk (methionine, asparagine, and trimethylamine) with equol + ODMA producers having lower concentrations, yet paradoxically higher pro-inflammatory cytokines. In urine, nonproducers clustered with ODMA producers and were distinct from equol + ODMA producers. Urinary metabolite profiles revealed significantly higher excretion of fumarate and 2-oxoglutarate, as well as pyroglutamate, alanine, and the gut microbial metabolite dimethylamine in equol + ODMA producers. CONCLUSION: These results emphasize that the serum and urine metabolomes are distinct based on the ability to metabolize isoflavones. PMID- 27364094 TI - Experience of integrating vitamin A supplementation into polio campaigns in the African Region. AB - INTRODUCTION: Vitamin A deficiency is a public health problem that affects children across the WHO African Region. Countries have integrated vitamin A supplementation in different child health interventions, most notably with polio campaigns. The integration of vitamin A in polio campaigns was documented as a best practice in Angola, Chad, Cote d'Ivoire, Tanzania, and Togo. There are potential risks to vitamin A supplementation associated with the polio endgame and certification in the African Region. METHODS: We reviewed the findings from the documentation of best practices assessment that was conducted by the WHO Regional Office for Africa in 2014 and 2015 in the five countries that noted integration of vitamin A with polio as a best practice. In addition, we reviewed the coverage rates for oral poliovirus vaccine and vitamin A supplementation in Angola, Chad, Cote d'Ivoire, Tanzania, and Togo in 2014 and 2015. RESULTS: Vitamin A deficiency in 2004 ranged from 35% in Togo to as high as 55% in Angola. All five countries integrated vitamin A supplementation in at least one campaign in 2013-2014 and all achieved over 80% coverage for vitamin A supplementation when it was integrated with polio. DISCUSSION: Given the progress of the polio program, and decreasing campaigns, there is a risk that fewer children will be reached each year with vitamin A supplementation. We recommend that for countries strengthen the integration of vitamin A supplementation with routine immunization services. PMID- 27364095 TI - Enhancing transit polio vaccination in collaboration with targeted stakeholders in Kaduna State, Nigeria: Lessons learnt: 2014-2015. AB - INTRODUCTION: In Kaduna State of Nigeria, the high influx of people from neighboring states with eligible children for polio vaccination represents a significant proportion of the target population. Many of these children are often missed by the vaccination team. The purpose of the study was to determine the contribution of targeted stakeholders in transit polio vaccination. METHODS: We used the trends of vaccinated children at transit points, motor parks and markets, well as total children vaccinated by transit teams in Chikun, Igabi and Sabon Gari Local Government Areas (LGAs) of Kaduna State, Nigeria, four rounds before and after the introduction of transit polio vaccination with targeted stakeholders in Kaduna State. RESULTS: A total of 87,502 under-5 children were vaccinated by the various transit teams in the three LGAs, which accounted for 3.2% of the total 2,781,162 children vaccinated by the three LGAs. For transit point vaccination, the number of vaccinated children increased from 1026 to 19,289 (302%), while motor park vaccination increased from 1289 to 4106 (318%) and market vaccination increased from 10,488 to 14,511 (138%), four rounds after the introduction of transit polio vaccination with targeted stakeholders. CONCLUSION: Engagement of targeted stakeholders significantly enhanced transit polio vaccination in Kaduna State, Nigeria. PMID- 27364096 TI - The predicted persistence and kinetics of antibody decline 9years after pre school booster vaccination in UK children. AB - BACKGROUND: Long term follow-up of vaccine trials is essential to establish the duration of protection. In the context of worldwide concern about rising pertussis incidence, estimates of antibody persistence after vaccination, which do not account for the rise in antibody due to natural boosting or infection, may overestimate the degree of protection afforded by pertussis vaccines. METHODS: This was a 5year follow up study of a randomised controlled trial of diphtheria, tetanus, pertussis and polio booster vaccines in UK children aged 3.5-5years. Antibody persistence was measured at 1month, 1, 3, and 5years after vaccination and the kinetics of antibody decline were modelled longitudinally. Estimates of predicted antibody persistence 9years after the pre-school booster were derived from model parameters. RESULTS: Antibody levels 9years after vaccination were predicted to be above accepted thresholds for protection for diphtheria, tetanus and polio. Antibody responses to pertussis toxoid were undetectable in 49% of children at the 5year follow up visit, and responses were predicted to be undetectable in 69% (95% CI 45-88%) of children by the time of their teenage booster at 13-14years of age. CONCLUSIONS: There is no defined correlate of protection for pertussis. However, the large proportion of participants in this study with undetectable pertussis antibody levels at both measured and predicted timepoints suggests sub-optimal immunity in adolescence. Adding pertussis to the teenage booster for UK children as is done in other countries, would enhance immunity in adolescence. PMID- 27364097 TI - Temperature-mediated recombinant anthrax protective antigen aggregate development: Implications for toxin formation and immunogenicity. AB - Anthrax vaccines containing recombinant PA (rPA) as the only antigen face a stability issue: rPA forms aggregates in solution after exposure to temperatures ?40 degrees C, thus losing its ability to form lethal toxin (LeTx) with Lethal Factor. To study rPA aggregation's impact on immune response, we subjected rPA to several time and temperature combinations. rPA treated at 50 degrees C for 30min formed high mass aggregates when analyzed by gel electrophoresis and failed to form LeTx as measured by a macrophage lysis assay (MLA). Aggregated rPA-formed LeTx was about 30 times less active than LeTx containing native rPA. Mice immunized with heat-treated rPA combined with Al(OH)3 developed antibody titers about 49 times lower than mice immunized with native rPA, as measured by a Toxicity Neutralization Assay (TNA). Enzyme Linked Immunosorbent Assay (ELISA) of the same immune sera showed anti-rPA titers only 2-7 times lower than titers elicited by native rPA. Thus, rPA's ability to form LeTx correlates with its production of neutralizing antibodies, and aggregation significantly impairs the protein's antibody response. However, while these findings suggest MLA has some value as an in-process quality test for rPA in new anthrax vaccines, they also confirm the superiority of TNA for use in vaccine potency. PMID- 27364098 TI - Exercise training contributes to H2O2/VEGF signaling in the lung of rats with monocrotaline-induced pulmonary hypertension. PMID- 27364099 TI - Association of baseline bleeding pattern on amenorrhea with levonorgestrel intrauterine system use. AB - OBJECTIVE: This study aims to evaluate the effect of baseline bleeding patterns on rates of amenorrhea reported at 12 months in levonorgestrel (LNG) 52 mg intrauterine system (IUS) users. We also assessed the effect of baseline bleeding patterns at 3 and 6 months postinsertion. STUDY DESIGN: In this secondary analysis of the Contraceptive CHOICE Project, we included participants who had an LNG-IUS inserted within 1 month of enrollment and continued use for 12 months. Using 12-month telephone survey data, we defined amenorrhea at 12 months of use as no bleeding or spotting during the previous 6 months. We used chi-square and multivariable logistic regression to assess the association of baseline bleeding pattern with amenorrhea while controlling for confounding variables. RESULTS: Of 1802 continuous 12-month LNG-IUS users, amenorrhea was reported by 4.9%, 14.8% and 15.4% of participants at 3, 6 and 12 months, receptively. Participants with light baseline bleeding or short duration of flow reported higher rates of amenorrhea at 3 and 6 months postinsertion (p<.03), while LNG-IUS users with heavy or prolonged flow were less likely to report amenorrhea at 3 and 6 months (p<.03). In a multivariable analysis, participants with self-reported heavy bleeding at baseline were less likely to report amenorrhea at 12 months than those who reported moderate bleeding (ORadj, 0.36; 95% CI, 0.16-0.69). CONCLUSION: Women with heavier menstrual bleeding are less likely than women with moderate flow to report amenorrhea following 12 months of LNG-IUS use. IMPLICATIONS: Baseline heavy menstrual flow reduces the likelihood of amenorrhea with LNG-IUS use, information that could impact contraceptive counseling. Anticipatory counseling can improve method satisfaction and continuation, an important strategy to continue to reduce unintended pregnancy and abortion rates. PMID- 27364100 TI - Safety of hormonal contraception and intrauterine devices among women with depressive and bipolar disorders: a systematic review. AB - BACKGROUND: Women with depressive or bipolar disorders are at an increased risk for unintended pregnancy. OBJECTIVE: To examine the safety of hormonal contraception among women with depressive and bipolar disorders. METHODS: We searched for articles published through January 2016 on the safety of using any hormonal contraceptive method among women with depressive or bipolar disorders, including those who had been diagnosed clinically or scored above threshold levels on a validated screening instrument. Outcomes included changes in symptoms, hospitalization, suicide and modifications in medication regimens such as increase or decrease in dosage or changes in type of drug. RESULTS: Of 2376 articles, 6 met the inclusion criteria. Of three studies that examined women clinically diagnosed with depressive or bipolar disorder, one found that oral contraceptives (OCs) did not significantly change mood across the menstrual cycle among women with bipolar disorder, whereas mood did significantly change across the menstrual cycle among women not using OCs; one found no significant differences in the frequency of psychiatric hospitalizations among women with bipolar disorder who used depot medroxyprogesterone acetate (DMPA), intrauterine devices (IUDs) or sterilization; and one found no increase in depression scale scores among women with depression using and not using OCs, for both those treated with fluoxetine and those receiving placebo. Of three studies that examined women who met a threshold for depression on a screening instrument, one found that adolescent girls using combined OCs (COCs) had significantly improved depression scores after 3 months compared with placebo, one found that OC users had similar odds of no longer being depressed at follow-up compared with nonusers, and one found that COC users were less frequently classified as depressed over 11 months than IUD users. CONCLUSIONS: Limited evidence from six studies found that OC, levonorgestrel-releasing IUD and DMPA use among women with depressive or bipolar disorders was not associated with worse clinical course of disease compared with no hormonal method use. PMID- 27364101 TI - An objective Bayesian analysis of a crossover design via model selection and model averaging. AB - Inference about the treatment effect in a crossover design has received much attention over time owing to the uncertainty in the existence of the carryover effect and its impact on the estimation of the treatment effect. Adding to this uncertainty is that the existence of the carryover effect and its size may depend on the presence of the treatment effect and its size. We consider estimation and testing hypothesis about the treatment effect in a two-period crossover design, assuming normally distributed response variable, and use an objective Bayesian approach to test the hypothesis about the treatment effect and to estimate its size when it exists while accounting for the uncertainty about the presence of the carryover effect as well as the treatment and period effects. We evaluate and compare the performance of the proposed approach with a standard frequentist approach using simulated data, and real data. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27364102 TI - LRRK2 interferes with aggresome formation for autophagic clearance. AB - Autosomal-dominant mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) account for the most common monogenic form of Parkinson's disease (PD). A link between autophagy dysregulation and LRRK2 has consistently been reported, but it remains poorly defined which step is targeted by LRRK2. Here, we sought to examine the effect of LRRK2 on the sequestration and degradation of aggregated protein complexes for autophagic clearance. Because two major intracellular protein degradation systems, the ubiquitin proteasome system and the autophagy, are functionally coupled, proteasome inhibition is suggested to activate autophagy. So, we induced protein quality control-associated autophagy using the proteasome inhibitor MG132 in differentiated SH-SY5Y cells and mice expressing G2019S mutant LRRK2 to uncover how the autophagy pathway is affected by LRRK2. We found that LRRK2 disrupted aggresome formation for autophagic clearance of accumulated protein aggregates. Specifically, we observed the following in differentiated SH-SY5Y cells with overexpressed wild-type and G2019S LRRK2: 1) large, clear, perinuclear aggresomes were not detected under MG132, instead, much smaller aggregates were broadly distributed in the cytosol; 2) enhanced accumulation of LC3-II and p62/ubiquitin-positive protein inclusions were noted; and 3) protein aggregates were not cleared even after a recovery period, which exacerbated the MG132-induced cytotoxicity. Notably, higher protein accumulation was detected in the brains of G2019S transgenic mice than in the brains of littermate control mice under proteasome inhibition. Our present findings provide insight into the precise mechanisms that underlie autophagy dysregulation in the brains of patients with PD with LRRK2 mutations. PMID- 27364103 TI - Production lost due to cervical cancer in Poland in 2012. AB - BACKGROUND: Poland has one of the highest cervical cancer mortality rates in Europe. It is related to the problem of late diagnosis and low attendance rate in screening programs. The objective of the study has been to assess the annual production loss due to the cervical cancer morbidity and mortality in Poland in 2012. The outcomes have been to provide comprehensive information on cervical cancer's influence on population's ability to work and its overall economic burden for the society. The study has also provided the methodological framework for disease-related production losses in Polish settings. MATERIAL AND METHODS: The human capital method was used. The production losses were calculated in both monetary and quantitative terms (working days lost) due to 4 following reasons: 1) temporary disability to work, 2) permanent disability, 3) informal care, and 4) mortality. RESULTS: Cervical cancer resulted in approx. 702 964 working days lost in 2012 due to absence at work for both patients and care givers and a total number of 957 678 working days lost due to patients' mortality. The total value of production lost was assessed at 111.4 million euros. More than 66% of this value was attributed to women's mortality. CONCLUSIONS: The calculation of production lost due to cervical cancer burden provides strong evidence to support adequate health promotion and disease prevention actions. Actions promoting cervical cancer screening should be intensified including workplace health promotion activities. Med Pr 2016;67(3):289-299. PMID- 27364104 TI - Risk of occupational exposure to the HBV infection in non-clinical healthcare personnel. AB - BACKGROUND: Occupational risk of blood-borne infections is investigated mostly among nurses and doctors, studies concerning non-clinical health personnel (nCHP) being rare. The analysis of the occupational exposure to the hepatitis B virus (HBV) infection and the history of vaccination against the HBV in the nCHP group has been the aim of the study. MATERIAL AND METHODS: A retrospective analysis of 458 cases of the occupational exposure to biological agents was conducted: group I - doctors (N = 121, 28%), group II - nursing staff (N = 251, 55%), group III - nCHP (N = 86, 19%). RESULTS: In the group III the source was usually unknown (group: I - 0.83%, II - 11.16%, III - 86.05%, p < 0.001), and the proportion of individuals vaccinated against hepatitis B before the exposure was the lowest (group: I - 98.35%, II - 97.19%, III - 77.91%, p < 0.001). In this group most exposures resulted from injuries caused by needles/sharps deposited in waste sacks (60%) or anywhere outside of the medical waste container (5%). The possibility of the HBV infection risk during the exposure was found in 25 cases and was significantly more frequent in the group III. The qualification for the HBV post-exposure prophylaxis was also significantly more frequent in the group III. CONCLUSIONS: The exposure to the occupational risk of the HBV infection also concerns the non-clinical healthcare personnel. The non-clinical healthcare personnel comprises one of the main groups of the HBV post-exposure recipients. It is essential to determine the causes of the low hepatitis B vaccination coverage in the nCHP and consider introduction of mandatory vaccination in this group in Poland. Med Pr 2016;67(3):301-310. PMID- 27364105 TI - Concomitant sensitization to glutaraldehyde and methacrylic monomers among dentists and their patients. AB - BACKGROUND: A multitude of methacrylic monomers is used in dentistry. Glutaraldehyde (G) is used in dental practice and consumer products as a broad spectrum antimicrobial agent. The purpose of our study is to evaluate the frequency and the risk of concomitant sensitization to some methacrylic monomers (methyl methacrylate (MMA), triethyleneglycol dimethacrylate (TEGDMA), ethyleneglycol dimethacrylate (EGDMA), 2,2-bis-[4-(2-hydroxy-3-methacrylo xypropoxy)phenyl]-propane (Bis-GMA), 2-hydroxy-ethyl methacrylate (2-HEMA) and tetrahydrofurfuryl methacrylate (THFMA)) and glutaraldehyde in students of dentistry, students from the dental technician school, dental professionals and dental patients. MATERIAL AND METHODS: A total of 262 participants were included in the study: students of dentistry, students from the dental technician school, dental professionals, and dental patients as a control group. All were patch tested with methacrylic monomers and glutaraldehyde. The results were subject to the statistical analysis (p < 0.05). RESULTS: Among the group of dental students, the highest frequency of concomitant sensitization was to TEGDMA and G (15.5%). In the group of patients the highest frequency of concomitant sensitization was to EGDMA and G (16.4%). The frequency of concomitant sensitization among dental professionals was much lower, with the highest rate to TEGDMA and G (7.7%), too. We consider the students from the dental technician school, where the exposure to glutaraldehyde is less likely, to be the group at a lesser risk of concomitant sensitization. CONCLUSIONS: Dental students and dental patients could be outlined as groups at the risk of concomitant sensitization to glutaraldehyde and methacrylic monomers. For dental professionals, we assumed an increased risk for concomitant sensitization to TEGDMA and aldehydes that are commonly used in dentistry. We consider the students from the dental technician school to be the group at a lesser risk of concomitant sensitization to glutaraldehyde and methacrylic monomers. Med Pr 2016;67(3):311-320. PMID- 27364106 TI - Dosages of ionizing radiation during limb diagnostic X-ray examinations. AB - BACKGROUND: X-ray examination is associated with the patient's exposure to ionizing radiation. The dose values depend on the type of the medical procedure used, the X-ray unit technical condition and exposure conditions selected by X ray technicians. The aim of this study has been to assess the entrance surface dose (ESD) values received by patients during the limb X-ray examination. The results should help doctors in making the decision about sending patients for X ray examination. At the same time the X-ray unit condition and examination method performance are important for the radiological protection of the medical staff. MATERIAL AND METHODS: The study covered the total number of 118 X-ray units located in 56 public healthcare entities and private medical centers in the Masovian Voivodeship. The measurement of the radiation dose rate received by patients was based on our own research procedures. RESULTS: The research has found that there are even more than 10-fold differences in the dose values received by adult patients with several-fold differences in the case of children patients. The broadest dose value range for adult patients was related to femur radiography. The ESD values for this procedure ranged 70.9-765.2 MUGy (with the average value of 319.7 MUGy). The broadest dose value range for children was related to the knee radiography. The range for children aged 5 years old was 11.8 95.8 MUGy (with the average value of 48.9 MUGy). CONCLUSIONS: It is essential to immediately implement X-ray room working procedures for the purpose of performing diagnostic examinations based on the existing model procedures. Med Pr 2016;67(3):321-326. PMID- 27364107 TI - [Occurrence of occupational diseases in Poland, 2014]. AB - BACKGROUND: The aim of the annual analysis of the incidence of occupational diseases in Poland is to evaluate the extent of the incidence and to identify its causes as well as activities involving factors that are harmful or annoying to such an extent that they result in occupational diseases. MATERIAL AND METHODS: Occupational diseases reporting forms supplied to the Central Register of Occupational Diseases were used as the study material. RESULTS: In 2014, there were 2351 cases of occupational diseases recorded, i.e., 16.5 cases per 100 thousand of employees. The most numerous categories comprised infectious or parasitic diseases (borreliosis), pneumoconiosis, voice disorders and hearing loss (in total 79.7% of cases). The main causative factors of occupational diseases were as follows: industrial dust containing free silica, tick transmitted Borrelia spirochete, and the way the work is done, including excessive vocal effort, and noise. The highest incidence per 100 thousand workers were recorded in mining and quarrying (296), manufacturing (24.9), education (24.6), agriculture and forestry (24.2) sectors. CONCLUSIONS: Compared with the previous year, there was a slight increase in the number of cases of certified occupational diseases (6.2%), primarily due to the increased incidence of Lyme disease. The incidence of voice disorders among teachers continues to vary considerably in individual provinces (0-11.3/10 000), reflecting the use of non uniform diagnostic and certification methods. Med Pr 2016;67(3):327-335. PMID- 27364108 TI - [Do hearing threshold levels in workers of the furniture industry reflect their exposure to noise?]. AB - BACKGROUND: The aim of the study was to analyze the hearing status of employees of a furniture factory with respect to their exposure to noise and the presence of additional risk factors of noise-induced hearing loss (NIHL). MATERIAL AND METHODS: Noise measurements, questionnaire survey and assessment of hearing, using pure tone audiometry, were carried out in 50 male workers, aged 20-57 years, directly employed in the manufacture of furniture. The actual workers' hearing threshold levels (HTLs) were compared with the predictions calculated according to PN-ISO 1999:2000 based on age, gender and noise exposure. RESULTS: Workers under study were exposed to noise at daily noise exposure levels of 82.7 94.8 dB (mean: 90.9 dB) for a period of 3-14 years. In all subjects, mean HTL at 500 Hz, 1000 Hz, 2000 Hz and 4000 Hz did not exceed 25 dB. Nevertheless, high frequency notches were found in 11% of audiograms. The actual workers' HTLs at 3000-6000 Hz were similar to those predicted using PN-ISO 1999:2000. There were statistical significant differences between HTLs in subgroups of people with higher (> 78 mm Hg) and lower (<= 78 mm Hg) diastolic blood pressure, smokers and non-smokers, and those working with organic solvents. Hearing loss was more evident in subjects affected by the additional risk factors specified above. CONCLUSIONS: The results confirm the need to consider, in addition to noise, also some other NIHL risk factors, such as tobacco smoking, elevated blood pressure, and co-exposure to organic solvents when estimating the risk of NIHL and developing the hearing conservation programs for workers. Med Pr 2016;67(3):337 351. PMID- 27364109 TI - [Spread of nano-objects in the air as a result of switching-on a microwave]. AB - BACKGROUND: Switching-on a microwave results in the creation of nano-sized particles, which can spread through the air of a given premise, e.g., room. MATERIAL AND METHODS: The study was carried out to determine the number and surface concentrations as well as the mean particles size using a DiscMini measurement device distributed in 6 measuring points to track changes of particle parameters, primarily at the source of particle creation and in the area of local ventilation (fume cupboard), and also in other places, e.g., near the window or in the middle of the room. RESULTS: Where the fume cupboard was switched-off, i.e., normal pressure ventilation in the room, switching-on the microwave caused a 9.42-14.14-fold increase in the number concentration of nano-sized particles relative to the background and a 3.51-4.81-fold increase in the surface concentration. Where the fume cupboard was switched-on, i.e., negative pressure ventilation in the room switching-on the microwave caused a 3.20-4.43-fold increase in the number concentration of nano-size particles relative to the background and a 1.61-1.89-fold increase in the surface concentration. CONCLUSIONS: The analysis of the data shows that switching-on a microwave for 5 min results in the creation of nano-objects already after about 3 min with the maximum concentration values after 12 min since switching-on the microwave in all 6 measurement points distributed in the test room. This applies to both situations, i.e., when the fume cupboard was switchedoff or switched-on. Med Pr 2016;67(3):353-363. PMID- 27364110 TI - [The way the quality of health services is perceived and treated by the managerial personnel of public hospitals]. AB - BACKGROUND: Managerial knowledge and skills as well as profound understanding of goals and objectives of management determine the effectiveness and efficiency in all areas of managerial activities. In particular, this applies to the quality of healthcare services, perceived as a compliance between the effects (of medical treatment) and the assumed relevant objectives (defined/desired health condition). The aim of the research was to distinguish and define the way the health service quality is perceived by the hospital managerial personnel. MATERIAL AND METHODS: The questionnaire was mailed to 836 members of the managerial personnel of public hospitals in the Lodz province. Of this number 122 questionnaires were returned. RESULTS: Only 22 (18.49%) of respondents presented the definition of quality. Attempts to meet patients' expectations and to satisfy them were found to be the prevailing perception of the healthcare quality and 96.64% of respondents considered competences of medical staff contributory. Almost 64% of respondents disagree with the opinion that the number of medical staff does not affect the service quality. According to the respondents, a 46% increase in financial resources on average could significantly improve the quality of healthcare services. More than half (66.76%) of respondents claim that healthcare services that are available cover 82% of patients' needs. Almost 57% (56.52%) of respondents consider that the subordinate- superior relationship influences their work involvement. According to 42.61% of respondents, the offered incentives encourage actions for the quality improvement. CONCLUSIONS: The results of the research indicate the need to develop a clear cut definition of the health service quality by the managerial personnel of public hospitals and to change their understanding, perception and treatment of the discussed issue, which provides a basis for the effective and efficient hospital management. Med Pr 2016;67(3):365-373. PMID- 27364111 TI - [Physicians' knowledge on the work-related chronic obstructive pulmonary disease]. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) may be induced by the work environment conditions. According to the estimates, 10-20% of all COPD cases are associated with occupational exposure to dusts and irritant gases. However, in 2014, only 11 cases of work-related COPD were recognized in Poland. The aim of the study was to analyze the reasons for the low incidence of work-related COPD in the context of pulmonologists' knowledge about occupational risk factors and procedures on reporting suspected occupational diseases. MATERIAL AND METHODS: A survey included 94 pulmonologists randomly selected out of 225 specialists registered at the Local Physicians Chamber in Lodz. The study was performed anonymously with the use of original questionnaire. RESULTS: More than a half of the surveyed pulmonologists identified environmental risk factors for COPD correctly, while only 23.4% properly identified the main occupational risk factors as the cause of COPD. Only 58.5% of the pulmonologists always asked their patients suffering from COPD about their job/profession and 60.6% of them did not have any knowledge about procedures on reporting suspected occupational diseases. CONCLUSIONS: The physicians rarely ask patients suffering from COPD about their job/profession and the relationship between their ailments and occupational exposure. What is more, they do not know legal regulations on proper referral of a patient with a suspected case of occupational disease. The results of the study clearly indicate that there is an urgent need for increasing pulmonologists' knowledge on work-related COPD. Med Pr 2016;67(3):375-384. PMID- 27364112 TI - [Multiwork and satisfaction with various life domains: Analysis of sex, gender, occupational and age differences]. AB - BACKGROUND: Contemporary multiwork definitely changes its face, and statistics show that Poland is in the forefront of European countries in terms of the number of multiworkers. The question arises whether the provision of work for more than one employer can influence personal and professional satisfaction, and whether job satisfaction, satisfaction with marriage and satisfaction with life are differentiated by sex, gender, age and a job position. MATERIAL AND METHODS: The study involved 218 multiworkers and 218 monoworkers. The subjects completed the following research tools: a survey, the Satisfaction with Life Scale, the Job Description Questionnaire, the Job Affect Scale, the Scale of Masculinity and Femininity. RESULTS: The research shows that multiwork differentiates satisfaction with organization and management. Sex, gender, age and job position affect the whole system of satisfaction dimensions, especially satisfaction with work and with life. Interaction of multiwork and age, sex, and job position differentiate satisfaction with certain aspects of job. CONCLUSIONS: The results of the study contribute to the deepening of knowledge about psychosocial functioning of multiworkers and the phenomenon of multiwork. Med Pr 2016;67(3):385-395. PMID- 27364113 TI - [Fullerenes: Characteristics of the substance, biological effects and occupational exposure levels]. AB - Fullerenes are molecules composed of an even number of carbon atoms of a spherical or an ellipsoidal, closed spatial structure. The most common fullerene is the C60 molecule with a spherical structure - a truncated icosahedron, compared to a football. Fullerenes are widely used in the diagnostics and medicine, but also in the electronics and energy industry. Occupational exposure to fullerene may occur during its production. The occupational concentrations of fullerenes reached 0.12-1.2 MU/m3 for nanoparticles fraction (< 100 nm), which may evidence low exposure levels. However, fullerene mostly agglomerates into larger particles. Absorption of fullerene by oral and respiratory routes is low, and it is not absorbed by skin. After intravenous administration, fullerene accumulates mainly in the liver but also in the spleen and the kidneys. In animal experiments there was no irritation or skin sensitization caused by fullerene, and only mild irritation to the eyes. Fullerene induced transient inflammation in the lungs in inhalation studies in rodents. Oral exposure does not lead to major adverse effects. Fullerene was not mutagenic, genotoxic or carcinogenic in experimental research. However, fullerene may cause harmful effects on the mice fetus when administered intraperitoneally or intravenously. Pristine C60 fullerene is characterized by poor absorption and low toxicity, and it does not pose a risk in the occupational environment. The authors of this study are of the opinion that there is no ground for estimating the maximum allowable concentration (NDS) of pristine fullerene C60. Fullerene derivatives, due to different characteristics, require separate analysis in terms of occupational risk assessment. Med Pr 2016;67(3):397-410. PMID- 27364114 TI - [Effects of radio- and microwaves emitted by wireless communication devices on the functions of the nervous system selected elements]. AB - Nervous system is the most "electric" system in the human body. The research of the effects of electromagnetic fields (EMFs) of different frequencies on its functioning have been carried out for years. This paper presents the results of the scientific literature review on the EMF influence on the functioning of the human nervous system with a particular emphasis on the recent studies of the modern wireless communication and data transmission systems. In the majority of the analyzed areas the published research results do not show EMF effects on the nervous system, except for the influence of GSM telephony signal on resting EEG and EEG during patients' sleep and the influence of radiofrequency EMF on the cardiovascular regulation. In other analyzed areas (EMF impact on sleep, the evoked potentials and cognitive processes), there are no consistent results supporting any influence of electromagnetic fields. Neurophysiological studies of the effect of radio- and microwaves on the brain functions in humans are still considered inconclusive. This is among others due to, different exposure conditions, a large number of variables tested, deficiencies in repeatability of research and statistical uncertainties. However, methodological guidelines are already available giving a chance of unifying research that definitely needs to be continued in order to identify biophysical mechanisms of interaction between EMFs and the nervous system. One of the EMF research aspects, on which more and more attention is paid, are inter-individual differences. Med Pr 2016;67(3):411 421. PMID- 27364115 TI - Recurrence of Tubulointerstitial Nephritis Without Uveitis, in a Patient with Previous Tubulointerstitial Nephritis and Uveitis Syndrome After Transplant. AB - We report a case of recurrent tubulointerstitial nephritis without uveitis in a patient with previous tubulointerstitial nephritis and uveitis syndrome after transplant. A 26-year-old male patient who had been diagnosed with tubulointerstitial nephritis and uveitis syndrome at 8 years of age developed end stage renal failure and subsequently underwent living-donor related renal transplant at 17 years old. The 1st recurrence of tubulointerstitial nephritis and uveitis occurred 36 months after transplant, which was treated with increased immunosuppressive drugs. Graft function worsened again to estimated glomerular filtration rate of 25 mL/min/1.73 m2 at 76 months after transplant. Transplant ultrasonography was unremarkable. Virology tests (including cytomegalovirus, BK virus, and Epstein-Barr virus tests) were all negative, with negative donor specific antibodies. Urine protein creatinine ratio was unremarkable. A biopsy showed chronic allograft rejection and graft sclerosis, and immunosuppressive medications were subsequently decreased. The patient's renal function continued to decline over the next 3 months, with estimated glomerular filtration rate showing 18 mL/min/1.73 m2, prompting a further renal biopsy that showed granulomatous interstitial nephritis and moderate interstitial fibrosis. This was consistent with a further relapse of tubulointerstitial nephritis but without uveitis. His renal function improved over the next few months after tacrolimus was reintroduced. PMID- 27364116 TI - Band-like transport in highly crystalline graphene films from defective graphene oxides. AB - The electrical transport property of the reduced graphene oxide (rGO) thin-films synthesized from defective GO through thermal treatment in a reactive ethanol environment at high temperature above 1000 degrees C shows a band-like transport with small thermal activation energy (Ea~10 meV) that occurs during high carrier mobility (~210 cm(2)/Vs). Electrical and structural analysis using X-ray absorption fine structure, the valence band photo-electron, Raman spectra and transmission electron microscopy indicate that a high temperature process above 1000 degrees C in the ethanol environment leads to an extraordinary expansion of the conjugated pi-electron system in rGO due to the efficient restoration of the graphitic structure. We reveal that Ea decreases with the increasing density of states near the Fermi level due to the expansion of the conjugated pi-electron system in the rGO. This means that Ea corresponds to the energy gap between the top of the valence band and the bottom of the conduction band. The origin of the band-like transport can be explained by the carriers, which are more easily excited into the conduction band due to the decreasing energy gap with the expansion of the conjugated pi-electron system in the rGO. PMID- 27364117 TI - Reply to: Accuracy and reproducibility of the ETDRS visual acuity chart: methodological issues. PMID- 27364118 TI - Is Helicobacter pylori the culprit behind central serous chorioretinopathy? PMID- 27364119 TI - Helicobacter pylori is the culprit behind central serous chorioretinopathy. PMID- 27364120 TI - En face Integrated Central Avascular Zone (EFICAZ): a noninvasive tool for correlating morphological and functional damage in central diabetic macular edema. AB - BACKGROUND: As numerous factors account for diabetic maculopathy, retinal thickness alone is poorly correlated to visual function in diabetic macular edema. En face optical coherence tomography (OCT) enables assessing retinal changes at specific layers. By averaging several planes, overall changes can be better appreciated. METHODS: Retrospective analysis of a consecutive group of 16 patients (30 eyes) with diabetic macular edema in at least one eye, was compared to a control group of 17 healthy subjects (34 eyes). Healthy volunteers and diabetic patients being seen as part of their regular care underwent swept source OCT fundus imaging. En face Integrated Central Avascular Zone (EFICAZ) was manually determined and measured on images obtained by swept-source optical coherence tomography (OCT). EFICAZ was then compared between both populations and, for diabetic patients, correlated with best corrected visual acuity, as measured by the Snellen chart. RESULTS: In healthy subjects, a moderate correlation was found between age and EFICAZ (Pearson's coefficient = 0.45, P = 0.01). In age-matched populations (mean age of 63 +/- 3.8 years for eight healthy subjects and 62.7 +/- 8.9 years for diabetic patients; P = 0.9), EFICAZ was significantly higher in diabetic than non-diabetic eyes (2.92 +/- 1.10 mm2 versus 1.86 +/- 0.53 mm2; P < 0.01). In diabetic patients, correlation between the size of EFICAZ and visual acuity (Pearson's correlation coefficient = -0 .72, P < 0.001) was stronger than between OCT measured central subfield retinal thickness and visual acuity (Pearson's correlation coefficient = -0.02, N.S). CONCLUSIONS: EFICAZ increases with age in normal subjects. It is significantly larger in diabetic than in non-diabetic subjects. It offers a better way to determine visual acuity than OCT measurement of central retinal thickness. This new approach, which takes into account several factors involved in diabetic maculopathy, could be useful in monitoring response to therapy. It can easily be combined with other modalities. PMID- 27364122 TI - Gp96-Ig/Costimulator (OX40L, ICOSL, or 4-1BBL) Combination Vaccine Improves T cell Priming and Enhances Immunity, Memory, and Tumor Elimination. AB - T-cell costimulation typically occurs in a defined microenvironment that is not recapitulated by agonistic antibody therapy. To deliver such stimulation under more favorable conditions, we investigated whether an allogeneic cell-based vaccine that secreted Fc-OX40L, Fc-ICOSL, or Fc-4-1BBL would activate and expand T cells comparably with systemically administered agonist antibodies. Among these costimulators, locally secreted Fc-OX40L provided superior priming of antigen specific CD8(+) T cells, compared with combinations with OX40 antibodies or vaccine alone. Vaccine-expressed Fc-OX40L also stimulated IFNgamma, TNFalpha, granzyme B, and IL2 by antigen-specific CD8(+) T cells similarly to OX40 antibodies, without off-target consequences such as proinflammatory cytokine induction. Vaccine-secreted Fc-OX40L increased CD127(+)KLRG-1(-) memory precursor cells during the contraction phase, resulting in improved proliferation upon secondary antigen challenge, as compared with OX40 antibody. A cell-based vaccine cosecreting gp96-Ig and Fc-OX40L led to even more pronounced tumor control, complete tumor rejection, and increased tumor antigen-specific T-cell proliferation, including in tumor-infiltrating lymphocytes, as compared with combinations of gp96-Ig vaccine and OX40 antibodies, in mice with established melanoma or colorectal carcinoma. These data suggest that local modulation of the vaccine microenvironment has unexpected advantages over systemic costimulation with agonistic antibodies, which may simplify the clinical translation of such combination immunotherapies into humans. Cancer Immunol Res; 4(9); 766-78. (c)2016 AACR. PMID- 27364121 TI - Hard-Wired Control of Bacterial Processes by Chromosomal Gene Location. AB - Bacterial processes, such as stress responses and cell differentiation, are controlled at many different levels. While some factors, such as transcriptional regulation, are well appreciated, the importance of chromosomal gene location is often underestimated or even completely neglected. A combination of environmental parameters and the chromosomal location of a gene determine how many copies of its DNA are present at a given time during the cell cycle. Here, we review bacterial processes that rely, completely or partially, on the chromosomal location of involved genes and their fluctuating copy numbers. Special attention will be given to the several different ways in which these copy-number fluctuations can be used for bacterial cell fate determination or coordination of interdependent processes in a bacterial cell. PMID- 27364123 TI - Environments Associated with Moderate-to-Vigorous Physical Activity and Sedentary Behavior of Colorectal Cancer Survivors. AB - PURPOSE: Physical activity (PA) is an effective intervention for improving the quality of life of colorectal cancer survivors (CRC) and may reduce the risk of cancer recurrence and cancer specific and all-cause mortality. However, most CRC survivors are not sufficiently active to receive these benefits. Sedentary behavior (SB) has also been linked to morbidity and mortality risk independent of activity level, thereby presenting an additional opportunity to improve health outcomes of CRC survivors. The built environment is known to influence PA and SB; however, little is known about where CRC survivors engage in PA and SB. The objective of this exploratory study was to objectively identify locations where CRC survivors engage in PA and SB in order to inform health promoting interventions. METHOD: Activity and location of CRC survivors (n = 31) was monitored for 1 week between January 2014 and April 2015 in Nova Scotia, Canada. Bouts of PA and SB were time-matched with GPS data to attribute bouts to specific geographic locations. RESULTS: Participants' home environment was the main location for both time spent in PA bouts (73.7 %) and time spent in SB bouts (90.5 %). CONCLUSION: This study is the first to objectively identify environments where CRC survivors are active and sedentary. These findings highlight the importance of considering the home environment when developing intervention strategies to increase PA and reduce SB in CRC survivors. PMID- 27364124 TI - Interleukin-9 promotes cell survival and drug resistance in diffuse large B-cell lymphoma. AB - BACKGROUND: Interleukin-9 (IL-9) was discovered as a helper T cell growth factor. It has long been recognized as an important regulator in allergic inflammation. Recent years it was discovered to induce cell growth and differentiation of multiple transformed cells. However, its oncogenic activities in B-cell lymphomas have not been reported in detail. METHODS: Serum levels of IL-9 in DLBCL patients were quantified by ELISA, and its clinical significance was analysed. The expression of IL-9 receptor (IL-9R) was investigated in lymphoma cell lines by RT PCR and western blot, respectively. In DLBCL cell lines LY1 and LY8, IL-9R genes were knocked down by RNA interference and stable transfected cells were selected with puromycin. Normal and final siIL-9R (and siControl) LY1 and LY8 cells were treated with IL-9 alone and in synergy with chemotherapeutic drugs. Cell proliferation and apoptosis were assessed by Brdu incorporation and flow cytometric analysis. The mRNA of apoptosis regulation genes were measured with real-time PCR. RESULTS: Elevated serum levels of IL-9 were detected in DLBCL patients (24/30) compared to healthy controls (0/15). Positive expression of IL-9 (defined as a serum level >=1 pg/ml) was correlated with lower serum albumin levels and high international prognostic index (IPI) scores. IL-9R was expressed in both mRNA and protein levels in the five lymphoma cell lines, including LY1, LY8, MINO, SP53 and Jurkat. In vitro studies showed that IL-9 directly induced proliferation and inhibited apoptosis in LY1 and LY8 cells. It protects LY1 and LY8 cells from prednisolone induced apoptosis, and promotes their proliferation that were inhibited by rituximab, vincristine and prednisolone. Its molecular mechanism may be concerned with upregulating expression of p21CIP1 gene. Knock down of IL-9R gene could reverse the effects of IL-9 on LY1 and LY8 cells. CONCLUSIONS: IL-9 is associated with clinical features of DLBCL patients. It promotes survival of DLBCL cells and reduces the sensitivities of tumor cells to chemotherapeutic drugs via upregulation of p21CIP1 genes. PMID- 27364125 TI - Valence and Conduction Band Densities of States of Metal Halide Perovskites: A Combined Experimental-Theoretical Study. AB - We report valence and conduction band densities of states measured via ultraviolet and inverse photoemission spectroscopies on three metal halide perovskites, specifically methylammonium lead iodide and bromide and cesium lead bromide (MAPbI3, MAPbBr3, CsPbBr3), grown at two different institutions on different substrates. These are compared with theoretical densities of states (DOS) calculated via density functional theory. The qualitative agreement achieved between experiment and theory leads to the identification of valence and conduction band spectral features, and allows a precise determination of the position of the band edges, ionization energy and electron affinity of the materials. The comparison reveals an unusually low DOS at the valence band maximum (VBM) of these compounds, which confirms and generalizes previous predictions of strong band dispersion and low DOS at the MAPbI3 VBM. This low DOS calls for special attention when using electron spectroscopy to determine the frontier electronic states of lead halide perovskites. PMID- 27364126 TI - Climate change impacts on pollination. PMID- 27364127 TI - Development: A new function of plant trichomes. PMID- 27364128 TI - Is modern wheat bad for health? PMID- 27364129 TI - Organic farming and deforestation. PMID- 27364130 TI - Are the claimed benefits of organic agriculture justified? PMID- 27364131 TI - Reply to 'Are the claimed benefits of organic agriculture justified?'. PMID- 27364132 TI - Reply to 'Organic farming and deforestation'. PMID- 27364133 TI - Plasma membrane: Negative attraction. PMID- 27364138 TI - Speed reading. PMID- 27364139 TI - Charge storage in oxygen deficient phases of TiO2: defect Physics without defects. AB - Defects in semiconductors can exhibit multiple charge states, which can be used for charge storage applications. Here we consider such charge storage in a series of oxygen deficient phases of TiO2, known as Magneli phases. These Magneli phases (TinO2n-1) present well-defined crystalline structures, i.e., their deviation from stoichiometry is accommodated by changes in space group as opposed to point defects. We show that these phases exhibit intermediate bands with an electronic quadruple donor transitions akin to interstitial Ti defect levels in rutile TiO2. Thus, the Magneli phases behave as if they contained a very large pseudo-defect density: 1/2 per formula unit TinO2n-1. Depending on the Fermi Energy the whole material will become charged. These crystals are natural charge storage materials with a storage capacity that rivals the best known supercapacitors. PMID- 27364140 TI - Cooperativity Has Empirical and Ultimate Levels of Explanation. AB - Controversy over the meaning of pharmacological parameters often arises because of a lack of appreciation of different hierarchical levels of analysis. In a recent letter in Trends in Pharmacological Sciences, Zhang and Kavana [1] concluded that my two-state model for allosterism lacks cooperativity, even though Figures 5 and 6 in my review [2] illustrate examples of how the two-state model yields specific cooperativity values. Here, I explain how the two-state model (receptor-state analysis) gives rise to the cooperativity parameter (alpha) of the allosteric ternary complex model (receptor-population analysis). PMID- 27364141 TI - [Laparoscopic versus open rectal cancer resection: oncologically equal?]. AB - The oncological equivalence of laparoscopic and open rectal cancer resection was evaluated in four multicenter randomized controlled trials. The COLOR II and the COREAN trials demonstrated oncological equivalence; however, the ACOSOG and the ALaCaRT studies came to a different conclusion. In the latter two studies a composite endpoint that assessed the quality of the mesorectal specimen, the completeness of tumor-free circumferential and distal resection margins was chosen. In both trials a higher success rate for open surgery was shown; nevertheless, the validity of this composite endpoint has not been proven and no conclusions on solid oncological endpoints can be drawn. The COLOR II and the COREAN trial therefore remain the only available studies which investigated solid oncological endpoints, such as local recurrence and disease-free survival over an adequate follow-up time period of 3 years; however, the comparability of the study groups at least of the COLOR II trial needs to be called into question as only the experience of the laparoscopic surgeons was assessed. With a local recurrence rate of 5 % in both groups the oncological quality seems nevertheless to be good; therefore, a systematically inadequate control group should not be assumed. At this point it can be concluded that a good oncological outcome can be achieved with laparoscopic rectal resection in the hands of experts. For a final assessment the long-term results of the on-going trials needs to be awaited. If the promising results for laparoscopic surgery of the COLOR II trial are confirmed laparoscopic rectal resection should be preferred to open resection in the future. This conclusion is based on the generally known perioperative benefits of minimally invasive surgery. PMID- 27364142 TI - Opioid America: Two Heroes and Two Culprits. PMID- 27364143 TI - Steady-state visually evoked potential correlates of human body perception. AB - In cognitive neuroscience, interest in the neuronal basis underlying the processing of human bodies is steadily increasing. Based on functional magnetic resonance imaging studies, it is assumed that the processing of pictures of human bodies is anchored in a network of specialized brain areas comprising the extrastriate and the fusiform body area (EBA, FBA). An alternative to examine the dynamics within these networks is electroencephalography, more specifically so called steady-state visually evoked potentials (SSVEPs). In SSVEP tasks, a visual stimulus is presented repetitively at a predefined flickering rate and typically elicits a continuous oscillatory brain response at this frequency. This brain response is characterized by an excellent signal-to-noise ratio-a major advantage for source reconstructions. The main goal of present study was to demonstrate the feasibility of this method to study human body perception. To that end, we presented pictures of bodies and contrasted the resulting SSVEPs to two control conditions, i.e., non-objects and pictures of everyday objects (chairs). We found specific SSVEPs amplitude differences between bodies and both control conditions. Source reconstructions localized the SSVEP generators to a network of temporal, occipital and parietal areas. Interestingly, only body perception resulted in activity differences in middle temporal and lateral occipitotemporal areas, most likely reflecting the EBA/FBA. PMID- 27364144 TI - Assessment of autonomic function in a cohort of patients with ANCA-associated vasculitis. AB - OBJECTIVE: To assess symptoms and objective parameters of autonomic dysfunction (AD) in patients with ANCA-associated vasculitides. METHODS: Symptoms and objective parameters of AD were assessed in patients with ANCA-associated vasculitis and in age-matched healthy controls. Autonomic symptoms were explored by COMPASS31, a validated questionnaire addressing symptoms of six autonomic domains (orthostatic, vasomotor, secretomotor, gastrointestinal, pupillomotor, and bladder dysfunction). Objective autonomic parameters consisted of expiratory/inspiratory (E/I) ratio during the deep breathing test (DBT), blood pressure response to cold pressor test (CPT), and skin conductance changes during mental arithmetic. RESULTS: 27 patients and 27 healthy controls have been enrolled. 27 patients and 27 controls completed COMPASS31. 21 patients and 18 controls underwent objective autonomic testing. Vasculitis patients had significantly higher COMPASS31 total scores than controls (median 10.4 vs 3.0; p = 0.005). In the sub-domain analysis, significant differences were seen in the vasomotor and the bladder domain (p = 0.004; p < 0.001, respectively). No correlation was found between COMPASS31 score and disease duration, number of affected organs, or Birmingham vasculitis activity score (BVAS). There was no significant difference in any of the objective autonomic parameters between patients and controls. In a subgroup analysis, no difference in objective autonomic parameters was found between patients with active disease (n = 12) and patients in remission (n = 7). CONCLUSION: Patients with ANCA-associated vasculitides commonly have symptoms of autonomic dysfunction that are independent of disease duration and disease severity. However, at least in this single-centre observation, there was no evidence of impaired autonomic regulation in three autonomic function tests in vasculitis patients. PMID- 27364145 TI - Articular shear injuries of the capitellum in adolescents. AB - BACKGROUND: Fractures of the capitellum are rare and are commonly classified into 4 types. Type II variants involve a shear injury with a mostly articular cartilage component and little subchondral bone. Symptoms upon presentation after these injuries are variable, and the diagnosis can be difficult to make in the immature skeleton. METHODS: We retrospectively reviewed 3 cases of type II capitellar fractures in adolescent athletes who presented for evaluation with the senior author. RESULTS: All patients were initially treated conservatively, without identification or treatment of the capitellar shear component of their injury. Unfortunately, radiocapitellar arthrosis rapidly developed in all 3 and required surgical intervention at our institution. At an average postoperative follow-up of 49 months from the index procedure, patients ultimately had positive outcomes despite advanced degenerative changes on imaging. One patient required 2 subsequent operations for mechanical symptoms and pain. DISCUSSION: The 3 reported cases represent adolescent, athletic patients with missed shear injuries to the capitellum. These patients exhibited low Disabilities of Arm, Shoulder and Hand scores and high Mayo Elbow Performance Scores at final follow-up, but each patient demonstrated advanced degenerative changes on imaging, and 1 patient required 2 subsequent operations for mechanical symptoms and pain. A high index of suspicion is necessary to identify this injury pattern, and proper plain radiographic imaging with a low threshold for advanced imaging is necessary. Although the overall long-term prognosis is unknown for these patients, early recognition likely would have changed the initial conservative management decision in each and, theoretically, might have altered the outcome for these patients. PMID- 27364146 TI - Intraoperative fluoroscopic assessment of proper prosthetic radial head height. AB - BACKGROUND: Selecting a properly sized radial head prosthesis is imperative during radial head replacement. Although there has been much emphasis on avoiding overlengthening of the radius, little has been studied about how to avoid shortening. The purpose of this study was to characterize how a radial head replacement appears on intraoperative fluoroscopy depending on the height of the prosthetic radial head. METHODS: Articular cartilage thickness of the radial head was measured in 9 cadaveric elbows. Radial head replacement was performed in each specimen with 4 different prosthetic head heights: 4 mm and 2 mm shortening, anatomic, and 2 mm overlengthening. Anteroposterior fluoroscopic images were obtained for each head height, and the prosthetic radial head height was measured at 3 forearm positions (supination, neutral, and pronation) using the subchondral bone of the lateral edge of the coronoid at the reference point. RESULTS: The mean cartilage thickness of the radial head was 1.3 +/- 0.4 mm. The prosthetic radial head appeared 2.2 +/- 0.4 mm more proximal than the subchondral bone of the coronoid lateral edge in anteroposterior radiographs when the articular surface of the prosthesis was completely even with the coronoid articular surface. Unlike the native radial head, a prosthetic radial head showed a significant change of height with different forearm rotation (P < .001). DISCUSSION: This study found that a perfectly anatomic radial head replacement appears overlengthened by approximately 2 mm in intraoperative radiographs. This finding can be useful in guiding the appropriate height of a prosthetic radial head. PMID- 27364147 TI - Acquiring Foreign Language Vocabulary Through Meaningful Linguistic Context: Where is the Limit to Vocabulary Learning? AB - The present studies examined the effects of varying degrees of unfamiliar vocabulary within written discourse on individuals' abilities to use linguistic context for the purposes of translation and comprehension (i.e., lexical inferencing). Prose varied in the number of foreign words introduced into each sentence (e.g., 0 through 7 content words per sentence). Furthermore, Krashen's Input Hypothesis and the Evaluation component of the Involvement Load Hypothesis were tested to determine the degree at which non-comprehensible input hinders the ability of a learner to successfully use linguistic context for translation and comprehension. Results indicated that, as the number of foreign words per sentence, i.e., non-comprehensible input, increased the ability to successfully translate foreign words and create situational models for comprehension begins to decrease especially beyond five unfamiliar words per sentence. This result suggests that there is an optimal level of effectiveness in the use of a linguistic context strategy for learning foreign language vocabulary, but also that there is a limit to the strategy's effectiveness. Implications and applications to the field of foreign language learning are discussed. PMID- 27364148 TI - An outbreak of tick-borne encephalitis associated with raw goat milk and cheese consumption, Croatia, 2015. AB - The aim of this report is to emphasize the risk of acquiring TBE by the consumption of raw milk and dairy products. In April-May 2015, we registered the first outbreak of tick-borne encephalitis in Croatia in seven members out of ten exposed persons who consumed raw goat milk or cheese from the same supplier. Infection was confirmed by TBEV enzyme-linked immunosorbent assay (ELISA) in all patients. None had been vaccinated nor had observed a tick bite. PMID- 27364149 TI - The impact of cancer diagnosis and treatment on employment, income, treatment decisions and financial assistance and their relationship to socioeconomic and disease factors. AB - PURPOSE: The financial impact of cancer diagnosis and treatment can be considerable to individuals and their households, leading to changes in treatment decision making. This study aimed to quantify effects on income and employment; describe how cost-related factors influence treatment decision making and need for financial assistance; and to identify patient sociodemographic factors associated with treatment decision making, use of financial assistance and financial effects. METHODS: A cross-sectional self-report questionnaire was administered to oncology outpatients from two hospitals in Australia: one regional and one metropolitan. RESULTS: Of 255 participants, 67 % indicated a change in employment and 63 % of those reported reduced household income since their diagnosis. Travel (15 %), loss of income (14 %) and cost of treatments (11 %) were commonly cited factors influencing treatment decision making. Seventy four percent of participants reported that they did not access financial assistance, with more than a third (37 %) of those being unaware that financial assistance was available. Being currently not employed and more recent diagnosis were associated with a reduced income since diagnosis. After adjusting for employment status and age, patients with private health insurance had higher odds of reporting that financial factors had influenced treatment decision making (OR = 2.5). CONCLUSION: Unemployment is a major driver of the financial impact of cancer. The costs of treatment may be particularly challenging for those with private health insurance who are more likely to be treated in the private health system where out-of-pocket costs are greater. Improved access to financial assistance is required to better avoid potential inequities. PMID- 27364150 TI - Evaluation of sarcopenia in small-cell lung cancer patients by routine chest CT. AB - BACKGROUND: Single cross-sectional area of muscle at the third lumbar vertebra (L3MA) is gold standard to estimate skeletal muscle mass (SMM), and L3 muscle index (L3MI, L3MA/height(2)) is used to determine sarcopenia. The purposes of this study were to evaluate the relationship between SMM indices determined by routine chest CT and L3MI in patients with small-cell lung cancer (SCLC) and to suggest chest CT-derived diagnostic criteria for sarcopenia. METHODS: Area of pectoralis muscles at the aortic arch (PMA) and at L1 (L1MA) was retrospectively measured on chest CT images of 90 consecutive SCLC patients. Pearson's correlation and multiple linear regression analysis were used to assess relationships between L3MI determined by PET/CT and pectoralis muscle index (PMI) and L1 muscle index (L1MI) determined by chest CT. RESULTS: The correlation between L1MI and L3MI was stronger than that between PMI and L3MI (r = 0.851 vs. r = 0.447, p < 0.001). Multivariable regression analysis showed that L1MI was the only significant predictor of L3MI; L3MI = 0.963 * L1MI + 10.336 (R (2) = 0.689, p < 0.001) for male and L3MI = 0.772 * L1MI + 16.518 (R (2) = 0.777, p < 0.001) for female. Using this relationship, estimated cutoffs of L1MI for sarcopenia were 46 cm(2)/m(2) for male and 29 cm(2)/m(2) for female (L3MI cutoffs for sarcopenia are 55 cm(2)/m(2) for male and 39 cm(2)/m(2) for female). The sensitivity and specificity of L1MI cutoffs to determine sarcopenia were 98.2 and 100 %, respectively. CONCLUSIONS: Chest CT-determined L1MI is highly correlated with L3MI in SCLC patients. L1MI, as determined by chest CT, could be used to determine the presence of sarcopenia with suggested cutoffs of 46 cm(2)/m(2) for men and 29 cm(2)/m(2) for women. PMID- 27364151 TI - The impact of cancer and quality of life among long-term survivors of breast cancer in Austria. AB - PURPOSE: This study explores the relationship between the perceived impact of cancer among long-term breast cancer survivors, sociodemographic and clinical variables, and mental and physical health-related quality of life outcomes in Austria. METHODS: One hundred and fifty-two long-term survivors of breast cancer (on average 13 years after initial diagnosis) completed three mailed surveys, including the Short Form-36 (SF-36), the Impact of Cancer (version 2) to assess the perceived positive and negative aspects of cancer survivorship, and a general sociodemographic and clinical questionnaire. Linear regression models were constructed to determine the effects of the perceived positive and negative impact of cancer on mental and physical health-related quality of life. RESULTS: Respondents reported a physical health status that centered on population norms for Austria, but scored lower on mental health status. After controlling for age, chemotherapy, exercise, and BMI, the positive impact of cancer was associated with improved physical functioning (p = 0.0014) and the negative impact of cancer was associated with poorer physical functioning (p < 0.0001). After controlling for age, marital status, the belief in emotional distress as a cause of cancer, and high stress levels, the negative impact of cancer was associated with poorer mental functioning (p < 0.0001). Higher perceived positive impact of cancer was not associated with improved mental functioning. CONCLUSIONS: Long-term survivors of breast cancer in Austria perceive both positive and negative impacts of breast cancer. These perceptions, in particular the negative impact of cancer, appear to influence, or are potentially influenced by, physical and mental health-related quality of life. PMID- 27364152 TI - Diagnostic efficacy and therapeutic impact of computed tomography in the evaluation of clinically suspected otosclerosis. AB - OBJECTIVE: To assess the diagnostic efficacy and therapeutic impact of CT in evaluating patients with clinically suspected otosclerosis. METHODS: CT scans performed over a 5-year period for clinically suspected otosclerosis were retrospectively reviewed. CT diagnoses were correlated with subsequent surgical management. For otosclerosis positive cases, clinically significant extensions of otosclerosis were correlated with audiometry and the diagnosis was correlated with surgical findings. RESULTS: Of 259 CT studies, 46 % of patients were positive, 49 % negative and 5 % equivocal for otosclerosis. A relevant alternative CT diagnosis was evident in 33 % of the negative studies. One targeted surgery was performed for every four CT studies. CT outcome influenced the decision to perform stapedectomy in 41 % CT-positive versus 4 % CT-negative patients. CT-positive ears for otosclerosis could not be predicted from baseline clinical or audiometric criteria. Those with endosteal extension demonstrated lower bone conduction thresholds presurgically. The positive predictive value of CT diagnosis of otosclerosis was 100 %. CONCLUSIONS: CT demonstrated a high rate of clinically relevant diagnoses in both CT-positive and -negative for otosclerosis patients, and this frequently influenced surgical management. CT also added value by demonstrating relevant extensions of the otosclerotic foci, some of which were predictive of audiometric parameters. KEY POINTS: * CT demonstrates a high rate of alternative diagnoses in suspected otosclerosis, 1:3. * CT results in a high rate of targeted surgery in suspected otosclerosis, 1:4. * CT prevents exploratory surgery in suspected otosclerosis. * Endosteal extension of otosclerosis is predictive of lower bone conduction tresholds presurgically. * The PPV of CT diagnosis of otosclerosis was 100 %. PMID- 27364153 TI - Cytotoxicity of the Roots of Trillium govanianum Against Breast (MCF7), Liver (HepG2), Lung (A549) and Urinary Bladder (EJ138) Carcinoma Cells. AB - Trillium govanianum Wall. (Melanthiaceae alt. Trilliaceae), commonly known as 'nag chhatri' or 'teen patra', is a native species of the Himalayas. It is used in various traditional medicines containing both steroids and sex hormones. In folk medicine, the rhizomes of T. govanianum are used to treat boils, dysentery, inflammation, menstrual and sexual disorders, as an antiseptic and in wound healing. With the only exception of the recent report on the isolation of a new steroidal saponin, govanoside A, together with three known steroidal compounds with antifungal property from this plant, there has been no systematic pharmacological and phytochemical work performed on T. govanianum. This paper reports, for the first time, on the cytotoxicity of the methanol extract of the roots of T. govanianum and its solid-phase extraction (SPE) fractions against four human carcinoma cell lines: breast (MCF7), liver (HEPG2), lung (A549) and urinary bladder (EJ138), using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazoliumbromide cytotoxicity assay and liquid chromatography and electrospray ionization quadrupole time-of-flight mass spectrometry analysis of the SPE fractions. The methanol extract and all SPE fractions exhibited considerable levels of cytotoxicity against all cell lines, with the IC50 values ranging between 5 and 16 ug/mL. Like other Trillium species, presence of saponins and sapogenins in the SPE fractions was evident in the liquid chromatography mass spectrometry data. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27364154 TI - Beyond the referendum. PMID- 27364155 TI - Structural characterization suggests models for monomeric and dimeric forms of full-length ezrin. AB - Ezrin is a member of the ERM (ezrin-radixin-moesin) family of proteins that have been conserved through metazoan evolution. These proteins have dormant and active forms, where the latter links the actin cytoskeleton to membranes. ERM proteins have three domains: an N-terminal FERM [band Four-point-one (4.1) ERM] domain comprising three subdomains (F1, F2, and F3); a helical domain; and a C-terminal actin-binding domain. In the dormant form, FERM and C-terminal domains form a stable complex. We have determined crystal structures of the active FERM domain and the dormant FERM:C-terminal domain complex of human ezrin. We observe a bistable array of phenylalanine residues in the core of subdomain F3 that is mobile in the active form and locked in the dormant form. As subdomain F3 is pivotal in binding membrane proteins and phospholipids, these transitions may facilitate activation and signaling. Full-length ezrin forms stable monomers and dimers. We used small-angle X-ray scattering to determine the solution structures of these species. As expected, the monomer shows a globular domain with a protruding helical coiled coil. The dimer shows an elongated dumbbell structure that is twice as long as the monomer. By aligning ERM sequences spanning metazoan evolution, we show that the central helical region is conserved, preserving the heptad repeat. Using this, we have built a dimer model where each monomer forms half of an elongated antiparallel coiled coil with domain-swapped FERM:C-terminal domain complexes at each end. The model suggests that ERM dimers may bind to actin in a parallel fashion. PMID- 27364156 TI - A CHRNB1 frameshift mutation is associated with familial arthrogryposis multiplex congenita in Red dairy cattle. AB - BACKGROUND: Bovine arthrogryposis multiplex congenita (AMC) is a syndromic term for a congenital condition characterized by multiple joint contractures. Rare inherited forms of bovine AMC have been reported in different breeds. For AMC in Angus cattle a causative genomic deletion encompassing the agrin (AGRN) gene, encoding an essential neural regulator that induces the aggregation of acetylcholine receptors (AChRs), is known. In 2015, three genetically related cases of generalized AMC affecting Red dairy calves were diagnosed in Denmark. RESULTS: The family history of three affected calves suggested an autosomal recessive inheritance. Single nucleotide polymorphism (SNP) genotyping showed a single genomic region of extended homozygosity of 21.5 Mb on chromosome 19. Linkage analysis revealed a maximal parametric LOD score of 1.8 at this region. By whole genome re-sequencing of the three cases, two private homozygous non synonymous variants were detected in the critical interval. Both variants, located in the myosin phosphatase Rho interacting protein (MPRIP) and the cholinergic receptor nicotinic beta 1 subunit gene (CHRNB1), were perfectly associated with the AMC phenotype. Previously described CHRNB1 variants in humans lead to a congenital myasthenic syndrome with impaired neuromuscular transmission. The cattle variant represents a single base deletion in the first exon of CHRNB1 (c.55delG) introducing a premature stop codon (p.Ala19Profs47*) in the second exon, truncating 96 % of the protein. CONCLUSIONS: This study provides the first phenotypically and genetically characterized example of a bovine AMC phenotype that represents an inherited neuromuscular disorder corresponding to human congenital myasthenic syndrome. The identified CHRNB1 loss of function variant is predicted to have a deleterious effect on fetal AChR function, which could explain the lethal phenotype reported in this study. The identification of this candidate causative mutation thus widens the known phenotypic spectrum of CHRNB1 mutations and enables selection against this pathogenic variant in Red dairy cattle. PMID- 27364157 TI - A Human Lectin Microarray for Sperm Surface Glycosylation Analysis. AB - Glycosylation is one of the most abundant and functionally important protein post translational modifications. As such, technology for efficient glycosylation analysis is in high demand. Lectin microarrays are a powerful tool for such investigations and have been successfully applied for a variety of glycobiological studies. However, most of the current lectin microarrays are primarily constructed from plant lectins, which are not well suited for studies of human glycosylation because of the extreme complexity of human glycans. Herein, we constructed a human lectin microarray with 60 human lectin and lectin like proteins. All of the lectins and lectin-like proteins were purified from yeast, and most showed binding to human glycans. To demonstrate the applicability of the human lectin microarray, human sperm were probed on the microarray and strong bindings were observed for several lectins, including galectin-1, 7, 8, GalNAc-T6, and ERGIC-53 (LMAN1). These bindings were validated by flow cytometry and fluorescence immunostaining. Further, mass spectrometry analysis showed that galectin-1 binds several membrane-associated proteins including heat shock protein 90. Finally, functional assays showed that binding of galectin-8 could significantly enhance the acrosome reaction within human sperms. To our knowledge, this is the first construction of a human lectin microarray, and we anticipate it will find wide use for a range of human or mammalian studies, alone or in combination with plant lectin microarrays. PMID- 27364159 TI - How does the B,F-monodoping and B/F-codoping affect the photocatalytic water splitting performance of g-C3N4? AB - By means of density functional theory (DFT) computations, we investigated the electronic and optical properties of B,F-monodoped and B/F-codoped graphitic carbon nitride (g-C3N4) to explore the doping effects on the photocatalytic performance of g-C3N4. It is found that F atom addition plays a key role in stabilizing the surface of g-C3N4 and facilitating B atom substitution into g C3N4. Among the different doping strategies, only B/F-codoping does not have localized states in the midgap, which act as recombination centers for the photogenerated electron-hole pairs. All the doping strategies in this study can improve the utilization ratio of visible light for the g-C3N4 photocatalyst. Considering the relationship of overpotential of water redox reaction over g-C3N4 and band edge positions with respect to the water redox potentials, only the F doped and B/F-codoped g-C3N4 satisfy the criterion for overall water splitting. In other words, the B/F-codoping strategy not only meets the demands of no recombination centers and enhances the visible light utilization ratio, but also satisfies the need of overpotential. Thus, B/F-codoped g-C3N4 is expected to be a promising photocatalyst for overall water splitting under visible light. PMID- 27364158 TI - Coordination of Metabolism and Virulence Factors Expression of Extraintestinal Pathogenic Escherichia coli Purified from Blood Cultures of Patients with Sepsis. AB - One of the trademarks of extraintestinal pathogenic Escherichia coli is adaptation of metabolism and basic physiology to diverse host sites. However, little is known how this common human pathogen adapts to permit survival and growth in blood. We used label-free quantitative proteomics to characterize five E. coli strains purified from clinical blood cultures associated with sepsis and urinary tract infections. Further comparison of proteome profiles of the clinical strains and a reference uropathogenic E. coli strain 536 cultivated in blood culture and on two different solid media distinguished cellular features altered in response to the pathogenically relevant condition. The analysis covered nearly 60% of the strains predicted proteomes, and included quantitative description based on label-free intensity scores for 90% of the detected proteins. Statistical comparison of anaerobic and aerobic blood cultures revealed 32 differentially expressed proteins (1.5% of the shared proteins), mostly associated with acquisition and utilization of metal ions critical for anaerobic or aerobic respiration. Analysis of variance identified significantly altered amounts of 47 proteins shared by the strains (2.7%), including proteins involved in vitamin B6 metabolism and virulence. Although the proteomes derived from blood cultures were fairly similar for the investigated strains, quantitative proteomic comparison to the growth on solid media identified 200 proteins with substantially changed levels (11% of the shared proteins). Blood culture was characterized by up-regulation of anaerobic fermentative metabolism and multiple virulence traits, including cell motility and iron acquisition. In a response to the growth on solid media there were increased levels of proteins functional in aerobic respiration, catabolism of medium-specific carbon sources and protection against oxidative and osmotic stresses. These results demonstrate on the expressed proteome level that expression of extraintestinal virulence factors and overall cellular metabolism closely reflects specific growth conditions. Data are available via ProteomeXchange with identifier PXD002912. PMID- 27364160 TI - Modulating adult neurogenesis through dietary interventions. AB - Three areas in the brain continuously generate new neurons throughout life: the subventricular zone lining the lateral ventricles, the dentate gyrus in the hippocampus and the median eminence in the hypothalamus. These areas harbour neural stem cells, which contribute to neural repair by generating daughter cells that then become functional neurons or glia. Impaired neurogenesis leads to detrimental consequences, such as depression, decline of cognitive abilities and obesity. Adult neurogenesis is a versatile process that can be modulated either positively or negatively by many effectors, external or endogenous. Diet can modify neurogenesis both ways, either directly by ways of food-borne molecules, or possibly by the modifications induced on gut microbiota composition. It is therefore critical to define dietary strategies optimal for the maintenance of the stem cell pools. PMID- 27364161 TI - Expression, Purification and Characterization of Recombinant Canine FGF21 in Escherichia coli. AB - The canine metabolic diseases, such as obesity and diabetes, have become a worldwide problem. Fibroblast growth factor 21 (FGF21) is a potent regulator which has many biological functions relative to metabolism regulation. It suggests that FGF21 plays important roles in regulating canine metabolic diseases. To acquire the recombinant canine FGF21 (rcFGF21) in Escherichia coli, the recombinant bacteria were induced by 0.5 mM IPTG for 16 hours at 16 degrees C, and the rcFGF21 protein was purified by Ni-NTA. 8 mg rcFGF21 was acquired from one liter bacteria. The rcFGF21 protein has specific immunoblot reactivity against anti-FGF21 and anti-His antibody. The in vivo experimental result showed that rcFGF21 can significantly reduce plasma glucose of STZ-induced diabetic mice. PMID- 27364162 TI - Cellular Functions of RNA-Binding Motif Protein 3 (RBM3): Clues in Hypothermia, Cancer Biology and Apoptosis. AB - Cell rapidly adapts to the harsh environment under certain conditions such as hypothermia and stress via activity of certain specific cold-shock proteins. Two cold shock proteins, RNA-binding motif protein 3 (RBM3) and coldinducible RNA binding proteins (CIRP), have been unveiled in human cells. RBM3, which is able to regulate their expression at the level of translation by binding to different transcripts, allows the cell to respond rapidly to environmental signals. Additionally, expression of RBM3 is induced under mild to moderate hypothermia, and stress. Stress-response pathways play an essential role in cancer. In different types of cancer, RBM3 is up regulated and correlated with favourable clinic- pathological features. RBM3 plays certain functions such as anti apoptotic, cell proliferation enhancement, and a proto-oncogene function. Furthermore, Hypothermia-induced neuroprotection up- regulates RBM3 in neuronal cells. In this review, the multifunctional nature of RMB3 is outlined through summarizing the evidences from in vitro and in vivo studies. PMID- 27364163 TI - Susceptibility status of Anopheles arabiensis (Diptera: Culicidae) commonly used as biological materials for evaluations of malaria vector control tools in Madagascar. AB - BACKGROUND: Madagascar is a malaria-endemic country with an increase in cases in recent years. In vector control using insecticide, a susceptible strain is necessary to evaluate insecticide efficacy, either for spraying or on nets. The susceptibility of Anopheles arabiensis from Antananarivo, Madagascar to two organophosphate, three pyrethroid, two carbamate, and one organochlorine insecticides was investigated. Since 2010, An. arabiensis strain has been maintained away from insecticide source during 110 generations with optimal insectarium conditions. METHODS: Bioassay were performed on adult mosquitoes to assess the susceptibility of An. arabiensis to insecticide-impregnated papers (malathion 5 %, fenitrothion 1 %, deltamethrin 0.05 %, permethrin 0.75 %, alphacypermethrin 0.05 %, bendiocarb 0.1 %, propoxur 0.01 %, and DDT 4 %) following World Health Organization Pesticide Evaluation Scheme guidelines. Bioassay using Center for Disease Control bottle tests were also used to detect mortality. Molecular assay were carried out to detect the presence of knock down resistance (kdr) mutation using PCR techniques. RESULTS: Anopheles arabiensis is fully susceptible with 100 % mortality to malathion, fenitrothion, deltamethrin, permethrin, alphacypermethrin, bendiocarb, propoxur, and DDT. No kdr gene was detected using PCR method. CONCLUSION: The strain An. arabiensis maintained in the insectarium of Institut Pasteur de Madagascar is a fully susceptible strain and can be used for insecticide evaluation. PMID- 27364164 TI - Leukocyte-Expressed beta2-Adrenergic Receptors Are Essential for Survival After Acute Myocardial Injury. AB - BACKGROUND: Immune cell-mediated inflammation is an essential process for mounting a repair response after myocardial infarction (MI). The sympathetic nervous system is known to regulate immune system function through beta adrenergic receptors (betaARs); however, their role in regulating immune cell responses to acute cardiac injury is unknown. METHODS: Wild-type (WT) mice were irradiated followed by isoform-specific betaAR knockout (betaARKO) or WT bone marrow transplantation (BMT) and after full reconstitution underwent MI surgery. Survival was monitored over time, and alterations in immune cell infiltration after MI were examined through immunohistochemistry. Alterations in splenic function were identified through the investigation of altered adhesion receptor expression. RESULTS: beta2ARKO BMT mice displayed 100% mortality resulting from cardiac rupture within 12 days after MI compared with ~20% mortality in WT BMT mice. beta2ARKO BMT mice displayed severely reduced post-MI cardiac infiltration of leukocytes with reciprocally enhanced splenic retention of the same immune cell populations. Splenic retention of the leukocytes was associated with an increase in vascular cell adhesion molecule-1 expression, which itself was regulated via beta-arrestin-dependent beta2AR signaling. Furthermore, vascular cell adhesion molecule-1 expression in both mouse and human macrophages was sensitive to beta2AR activity, and spleens from human tissue donors treated with beta-blocker showed enhanced vascular cell adhesion molecule-1 expression. The impairments in splenic retention and cardiac infiltration of leukocytes after MI were restored to WT levels via lentiviral-mediated re-expression of beta2AR in beta2ARKO bone marrow before transplantation, which also resulted in post-MI survival rates comparable to those in WT BMT mice. CONCLUSIONS: Immune cell expressed beta2AR plays an essential role in regulating the early inflammatory repair response to acute myocardial injury by facilitating cardiac leukocyte infiltration. PMID- 27364166 TI - Persistent sciatic artery associated with solitary kidney and maldevelopment of mesonephric duct and urogenital sinus. PMID- 27364167 TI - Fusion angle affects intervertebral adjacent spinal segment joint forces-Model based analysis of patient specific alignment. AB - This study addresses the hypothesis that adjacent segment intervertebral joint loads are sensitive to the degree of lordosis that is surgically imposed during vertebral fusion. Adjacent segment degeneration is often observed after lumbar fusion, but a causative mechanism is not yet clearly evident. Altered kinematics of the adjacent segments and potentially nonphysiological mechanical joint loads have been implicated in this process. However, little is known of how altered alignment and kinematics influence loading of the adjacent intervertebral joints under consideration of active muscle forces. This study investigated these effects by simulating L4/5 fusions using kinematics-driven musculoskeletal models of one generic and eight sagittal alignment-specific models. Models featured different spinopelvic configurations but were normalized by body height, masses, and muscle properties. Fusion of the L4/5 segment was implemented in an in situ (22 degrees ), hyperlordotic (32 degrees ), and hypolordotic (8 degrees ) fashion and kinematic input parameters were changed accordingly based on findings of an in vitro investigation. Bending motion from upright standing to 45 degrees forward flexion and back was simulated for all models in intact and fused conditions. Joint loads at adjacent levels and moment arms of spinal muscles experienced changes after all types of fusion. Hypolordotic configuration led to an increase of adjacent segment (L3/4) shear forces of 29% on average, whereas hyperlordotic fusion reduced shear by 39%. Overall, L4/5 in situ fusion resulted in intervertebral joint forces closest to intact loading conditions. An artificial decrease in lumbar lordosis (minus 14 degrees on average) caused by an L4/5 fusion lead to adverse loading conditions, particularly at the cranial adjacent levels, and altered muscle moment arms, in particular for muscles in the vicinity of the fusion. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:131-139, 2017. PMID- 27364165 TI - A Complex Interaction Between Reduced Reelin Expression and Prenatal Organophosphate Exposure Alters Neuronal Cell Morphology. AB - Genetic and environmental factors are both likely to contribute to neurodevelopmental disorders including schizophrenia, autism spectrum disorders, and major depressive disorders. Prior studies from our laboratory and others have demonstrated that the combinatorial effect of two factors-reduced expression of reelin protein and prenatal exposure to the organophosphate pesticide chlorpyrifos oxon-gives rise to acute biochemical effects and to morphological and behavioral phenotypes in adolescent and young adult mice. In the current study, we examine the consequences of these factors on reelin protein expression and neuronal cell morphology in adult mice. While the cell populations that express reelin in the adult brain appear unchanged in location and distribution, the levels of full length and cleaved reelin protein show persistent reductions following prenatal exposure to chlorpyrifos oxon. Cell positioning and organization in the hippocampus and cerebellum are largely normal in animals with either reduced reelin expression or prenatal exposure to chlorpyrifos oxon, but cellular complexity and dendritic spine organization is altered, with a skewed distribution of immature dendritic spines in adult animals. Paradoxically, combinatorial exposure to both factors appears to generate a rescue of the dendritic spine phenotypes, similar to the mitigation of behavioral and morphological changes observed in our prior study. Together, our observations support an interaction between reelin expression and chlorpyrifos oxon exposure that is not simply additive, suggesting a complex interplay between genetic and environmental factors in regulating brain morphology. PMID- 27364168 TI - Shapes of minimal-energy DNA ropes condensed in confinement. AB - Shapes of a single, long DNA molecule condensed in a confinement of a virus capsid are described as conformations optimizing a model free energy functional accounting for the interplay between the bending energy of the DNA and the surface energy of the DNA bundled in a "rope". The rope is formed by bundled DNA brought together by (self-)attractive interactions. The conformations predicted by the model depend on the shape of the confinement, the total amount of the packed DNA but also on the relative contributions of the bending and surface energies. Some of the conformations found were not predicted previously, but many previously proposed DNA conformations, some of which are seemingly contradictory, were found as the solutions of the model. The results show that there are many possible packing conformations of the DNA and that the one which realizes in a particular virus depends on the capsid geometry and the nature of condensing agents. PMID- 27364169 TI - Prevalence and associated factors of cardio-metabolic risk factors in Iranian seafarers. AB - BACKGROUND: Since Iran's economy is based on the sale of petroleum products, seafaring is considered a crucial job. Little research has been done on issues related to seafarers' health in Iranian maritime industry. The present study investigated the prevalence and associated factors of cardio-metabolic risk factors in seafarers of National Iranian Tanker Company (NITC). MATERIALS AND METHODS: A cross-sectional study was performed on 234 Iranian male seafarers of NITC in 2015. Metabolic syndrome (MetS) was diagnosed according to the reports of National Committee of Obesity. Three main blood parameters (of elevated total cholesterol, elevated low-density lipoprotein cholesterol, and elevated very low density lipoprotein cholesterol) and general obesity were included as additional cardio-metabolic risk factors. RESULTS: The mean age of the participants was 36.0 +/- 10.3 years. The prevalence of MetS was 14.9%. The common cardio-metabolic risk factors were excess weight (51.1%), abdominal obesity (38.5%), and smoking (27.8%) among Iranian seafarers. In multivariate analysis, age (OR: 1.05, 95% CI: 1.01-1.09) and body mass index (OR: 1.14, 95% CI: 1.01-1.27) were associated with the increase in hypertension risk. CONCLUSIONS: Our finding showed that the current prevalence of MetS among Iranian male seafarers working on tankers can affect negatively their health and career at sea. PMID- 27364170 TI - Air travel-related symptomatic deep venous thrombosis in cruise ship passengers. AB - BACKGROUND: Long air travel is a risk factor for deep venous thrombosis (DVT). The aim of the study was to report the occurrence of symptomatic DVT cases in cruise ship passengers after long haul flights and to discuss applied diagnostic methods. MATERIALS AND METHODS: A retrospective analysis of medical records of adult patients diagnosed with DVT in medical facility of the passenger ship was performed. On the basis of clinical examinations, B-mode ultrasound scans of the lower extremity venous systems, international normalised ratio (INR) tests, working diagnoses of DVT were established. The Wells score was used for stratification. Within 4-48 h of the diagnosis, D-dimer tests in blood, ultrasound Duplex examinations and specialists' consultations of DVT suspected patients were performed ashore. RESULTS: A study showed 3 (0.15%) patients suspected of DVT of a total number of 2,007 passengers who have completed a flight > 8 h in the analysed period. The medial time from the embarkation to the onset of symptoms was 68.7 h. Based on the Wells DVT score, in 2 (0.1%) patients the probability of DVT was determined to be likely. Both the ultrasound examinations and D-dimer tests were positive. Those patients were diagnosed by shore specialists as DVT. One (0.05%) patient determined as DVT unlikely according to the Wells scale, her INR indicated hypercoagulable state, but Duplex scan as well D-dimer test were negative and DVT suspicion was excluded. CONCLUSIONS: A clinical suspicion of DVT among passengers who joined the ship after their long haul flights could be an important diagnostic problem for ship's doctors. The Wells scale allows to stratify the risk, but to rule out suspicion of DVT, a negative result of D-dimer test must be demonstrated. A portable ultrasound device helps in onboard clinical evaluation of DVT suspected patients. Due to possible fatal complications of DVT which can lead to pulmonary embolism and cause medico-legal issues, a definitive diagnosis should only be obtained in cooperation with land-based health care providers. PMID- 27364171 TI - Development of software for handling ship's pharmacy. AB - BACKGROUND: Ships are required to carry a given amount of medicinal products and medications depending on the flag and the type of vessel. These medicines are stored in the so called ship's "medicine chest" or more properly - a ship pharmacy. Owing to the progress of medical sciences and to the increase in the mean age of seafarers employed on board ships, the number of pharmaceutical products and medical devices required by regulations to be carried on board ships is increasing. This may make handling of the ship's medicine chest a problem primarily on large ships sailing on intercontinental routes due to the difficulty in identifying the correspondence between medicines obtained abroad with those available at the national market. To minimise these problems a tool named Pharmacy Ship (acronym: PARSI) has been developed. MATERIALS AND METHODS: The application PARSI is based on a database containing the information about medicines and medical devices required by different countries regulations. In the first application the system was standardised to comply with the Italian regulations issued on the 1st October, 2015 which entered into force on the 18 January 2016. RESULTS: Thanks to PARSI it was possible to standardize the inventory procedures, facilitate the work of maritime health authorities and make it easier for the crew, not professional in the field, to handle the 'medicine chest' correctly by automating the procedures for medicines management. As far as we know there are no other similar tools available at the moment. The application of the software, as well as the automation of different activities, currently carried out manually, will help manage (qualitatively and quantitatively) the ship's pharmacy. CONCLUSIONS: The system developed in this study has proved to be an effective tool which serves to guarantee the compliance of the ship pharmacy with regulations of the flag state in terms of medicinal products and medications. Sharing the system with the Telemedical Maritime Assistance Service may result in avoiding mistakes in drug administration. Last but not least the availability of PARSI could help reduce/ avoid problems with maritime health authorities in case any of the required medicinal products are missing. PMID- 27364172 TI - Bleeding management in remote environment: the use of fresh whole blood transfusion and lyophilised plasma. AB - To mitigate medical risks in remote environments, the authors have implemented an innovative integrated medical support solution for bleeding management on board ships since 2013. Fresh whole blood transfusion (FWBT) and lyophilised plasma were put in place to address life threatening haemorrhages in maritime operations in the Arctic and Antarctica. The authors are illustrating the bleeding risks with an actual case occurring in Antarctica prior to the implementation of these procedures. They are presenting the different steps involved in the complex process of FWBT, from blood donors' qualifications to actual transfusions. The pros and cons of blood transfusion in extreme remote environment are discussed, including the training of health care professionals, equipment requirements, legal and ethical issues, decision making in complex blood group matching, medical benefits and risks. PMID- 27364173 TI - Benefits of photograph transmission for trauma management in isolated areas: cases from the French tele-medical assistance service. AB - French maritime tele-medical assistance is currently performed by a telephone consultation associated with complementary transmission of data (photographs, electrocardiograms, etc.) over the internet. Five case reports are presented to illustrate how photo transmission is useful to managing initial care and monitoring isolated patients. Case reports included: Case 1: management of a hand burn; Case 2: management of a finger wound; Case 3: management of an ocular foreign body; Case 4: management of a subungual haematoma; Case 5: management of phlegmon. In conclusions, photo transmission improves our practice of maritime tele-medical medicine. New high-definition technologies will help in the development of videoconferences on ships. PMID- 27364174 TI - Prevalence of cannabis and cocaine consumption in French fishermen in South Atlantic region in 2012-2013 and its policy consequences. AB - BACKGROUND: The aim of the study was to evaluate the use of cannabis and cocaine among fishermen followed in occupational medicine in the ports of Aquitaine and Charente-Maritime (Direction interregionale de la mer Sud-Atlantique [DIRM-SA]). MATERIALS AND METHODS: Thousand fishermen could be recruited during medical regulatory examination by the occupational physicians and nurses of Occupational Health Department for Seamen. RESULTS: About 20% of fishermen were former smokers. A third of the fishermen are at risk for excessive drinking according to the AUDIT-C. The prevalence of cannabis experimentation was estimated at 58%. The prevalence of positive urine test for cannabis was 28%. The prevalence of experimentation with cocaine was about 16%. The prevalence of positive urine test for cocaine was 4.5%. CONCLUSIONS: In accordance with its objectives, this study allows objectifying cannabis and cocaine consumption among fishermen. The national rules for fitness at sea have to be modified by introducing the use of urinary tests by occupational physician. PMID- 27364175 TI - The workload of fishermen: a cross sectional survey among Danish commercial fishermen. AB - BACKGROUND: Fishery has always been perceived as a physically demanding industry of a manual character. In recent years the physical work environment has developed positively and consequently the current situation in not fully described in the existing literature. This study aims to describe the work environment of Danish fishermen with regard to their physical workload and ergonomic factors. MATERIALS AND METHODS: A cross sectional study was performed on a random sample of active Danish commercial fishermen (response rate: 28%) by means of a questionnaire on demographic and self-reported occupational and health data. Questions covering the physical workload were related to seven different work situations and a score summing up the workload was developed for the analysis of the relative impact on different groups of fishermen. RESULTS: Almost all fishermen (96.2%) were familiar to proper lifting techniques but only 55.4% used them in their daily work. Standing work was the most applied work position (81.8%), while repetitive hand and finger movements and twisting and bending in the back were other frequent work situations. Deckhands had higher workload scores than skippers, while crew on Danish seiners had higher workload scores than fishermen in other vessel types. CONCLUSIONS: Despite improved work environment in the Danish fishing industry, fishermen still experience high levels of workload and suboptimal ergonomic conditions, which are known to cause pain and impair musculoskeletal health. To address the specific areas of fishing with the highest workload, future investments in assistive devices to ease the demanding work and reduce the workload, should particularly address deckhands and less mechanized vessels. PMID- 27364176 TI - Thermophysiological responses and work strain in fishermen on deep-sea fishing vessels. AB - BACKGROUND: Fishermen working on deep-sea vessels in the Barents and Norwegian Sea are exposed to low air temperatures, strong winds, high humidity, rain, snow and work at different intensities. Few studies have investigated the effect of environmental work factors on the physiology of this occupational group. The aim of the study was to investigate work strain and thermophysiological responses of fishermen on the trawl and factory decks of deep-sea vessels. MATERIALS AND METHODS: Twenty-five professional male fishermen (age 39 +/- 13 years) were recruited to the study which was performed on three trawlers in the Norwegian Sea in April, June and August 2014. During a six-hour shift, heart rate (HR), core (Tc) and mean skin (Ts) temperatures were recorded, and questions about subjective thermal sensation and comfort were answered. RESULTS: Short periods of hard (above 86% of HRmax) work raised Tc by 0.8 degrees C to 37.8 degrees C and decreased Ts by 2.3 degrees C to 29.8 degrees C during work on the trawl deck, and subjects reported being warm and sweaty. On the factory deck long periods of fairly light (between 52% and 66% HRmax) work, Tc of 37.4 degrees C and Ts of 30.9 degrees C were measured. CONCLUSIONS: Fishermen experience intermittent periods of heavy work on the trawl deck shown with elevated core temperature and HR. Work on the factory deck includes long periods of repetitive work with light to moderate work strain. A better understanding of work strain and environmental challenges during work on Norwegian deep-sea vessels will help identify exposure risks during work in the cold and heat. PMID- 27364177 TI - Environmental and health impact assessment for ports in Thailand. AB - Port development in Thailand is an essential part of the national maritime interest in connection with ship and shore activities. The growth of maritime industry and transportation has led to the expansion of ports' areas and capacity. Each port type causes different environmental impacts. Therefore, the Port Authority of Thailand has set up guidelines on ports' environmental management. This is divided into 3 major phases; namely, planning, construction and operation commencement periods. The Report of Environmental and Health Impact Assessment (EIA, HIA and EHIA) is regarded as the environmental management process in the planning period. It is a key tool to anticipate and prevent any adverse effects that might occur on the environment as well as community health resulting from the project implementation. This measure, in turn, creates advance preparation on both the preventive and problem-solving means before the project gets off the ground. At present, the majority of new projects on port development have still been in the process of information gathering for EHIA submission. Some cannot start to operate due to their EHIA failure. For example, the Tha-sala port which did not pass EHIA, mainly because emphasis had been focused on adhering to legal regulations without taking into consideration the in-depth analysis of data being conducted by community entities in the area. Thus caused the project to be finally abolished. Impact assessment on environment and health should be aimed at detailed understanding of the community in each particular area so that effective data of objective achievement in preventing environmental problems could actually be carried out and welcomed by the concerned society. PMID- 27364178 TI - "Christ offered salvation, and not an easy life": How do port chaplains make sense of providing welfare for seafarers? An idiographic, phenomenological approach analysis. AB - BACKGROUND: The shipping industry has historically leaned towards a biomedical model of health when assessing, treating and caring for seafarers. In recent years there has been more concern for the mental health of seafarers in both the academic literature and the commercial world, however, the psychological and emotional well-being of seafarers still largely falls on the shoulders of the port chaplains. The aim of the study was to explore how port chaplains make sense of providing welfare for seafarers by taking an idiographic, phenomenological approach (IPA). MATERIALS AND METHODS: Six male participants working as chaplains in United Kingdom ports took part in recorded face-to-face, semi-structured interviews covering three areas of questioning: role, identity and coping. Interviews were transcribed verbatim, and data analysed using interpretative phenomenological analysis. RESULTS: Three super-ordinate themes were identified from participants accounts; "We walk a very strange and middle path", "Exploited" and "Patching up". Rich data emerged in relation to the personal impact chaplains felt they made, which was facilitated by the historical role of the Church; this led to the second super-ordinate theme of how chaplains felt towards seafarers. Lastly, the analysis demonstrates how chaplains adapt to the limitations forced upon them to provide welfare, and a degree of acceptance at the injustice. CONCLUSIONS: Results were discussed in reference to theoretical models, including self-efficacy, empathic responding and the transactional model of stress and coping. Chaplains in ports perform their role autonomously with no input from healthcare professionals. Recommendations are made for a biopsychosocial model of health involving primary care, benefiting the health and well-being of seafarers and providing support and guidance for port chaplains at the frontline of welfare for seafarers. PMID- 27364181 TI - ? PMID- 27364179 TI - Zika virus infection: what should we not forget? PMID- 27364182 TI - Combined neprilysin and renin-angiotensin system inhibition in heart failure with reduced ejection fraction: a meta-analysis. AB - AIMS: The combined neprilysin/renin-angiotensin system (RAS) inhibitor sacubitril/valsartan reduced cardiovascular death or heart failure hospitalization, cardiovascular death, and all-cause mortality in a large outcomes trial. While sacubitril/valsartan is the only currently available drug in its class, there are two prior clinical trials in heart failure with omapatrilat, another combined neprilysin/RAS inhibitor. Using all available evidence can inform clinicians and policy-makers. METHODS AND RESULTS: We performed a meta-analysis using data from three trials in heart failure with reduced EF that compared combined neprilysin/RAS inhibition with RAS inhibition alone and reported clinical outcomes: IMPRESS (n = 573), OVERTURE (n = 5770), and PARADIGM-HF (n = 8399). We assessed the pooled hazard ratio (HR) for all-cause death or heart failure hospitalization, and for all-cause mortality in random effects models, comparing combined neprilysin/RAS inhibition with ACE inhibition alone. The composite outcome of death or heart failure hospitalization was reduced numerically in patients receiving combined neprilysin/RAS inhibition in all three trials, with a pooled HR of 0.86, 95% confidence interval (CI) 0.76 0.97, P = 0.013. For the endpoint of all-cause mortality, the pooled HR was 0.88, 95% CI 0.80-0.98, P = 0.021. Combined neprilysin/RAS inhibition compared with ACE inhibition was associated with more hypotension, but less renal dysfunction and hyperkalaemia in all three trials. CONCLUSIONS: Pooled estimates from three trials with two separate drugs of combined neprilysin/RAS inhibition support the use of combined neprilysin/RAS inhibition in heart failure with reduced EF. PMID- 27364183 TI - Cognitive Development Trajectories of Very Preterm and Typically Developing Children. AB - Cognitive impairment is common among children born very preterm (VPT), yet little is known about how this risk changes over time. To examine this issue, a regional cohort of 110 VPT (<= 32 weeks gestation) and 113 full-term (FT) born children was prospectively assessed at ages 4, 6, 9, and 12 years using the Wechsler Preschool and Primary Scale of Intelligence-Revised and then Wechsler Intelligence Scale for Children, 4th ed. At all ages, VPT children obtained lower scores than their FT born peers (p < .001). Growth curve modeling revealed stable cognitive trajectories across both groups. Neonatal white matter abnormalities and family socioeconomic adversity additively predicted cognitive risk. Despite some intraindividual variability, cognitive functioning of typically developing and high-risk VPT children was stable and influenced by early neurological development and family rearing context. PMID- 27364185 TI - Adrenal ganglioneuroma in a pregnant woman. PMID- 27364184 TI - Haptic contents of a movie dynamically engage the spectator's sensorimotor cortex. AB - Observation of another person's actions and feelings activates brain areas that support similar functions in the observer, thereby facilitating inferences about the other's mental and bodily states. In real life, events eliciting this kind of vicarious brain activations are intermingled with other complex, ever-changing stimuli in the environment. One practical approach to study the neural underpinnings of real-life vicarious perception is to image brain activity during movie viewing. Here the goal was to find out how observed haptic events in a silent movie would affect the spectator's sensorimotor cortex. The functional state of the sensorimotor cortex was monitored by analyzing, in 16 healthy subjects, magnetoencephalographic (MEG) responses to tactile finger stimuli that were presented once per second throughout the session. Using canonical correlation analysis and spatial filtering, consistent single-trial responses across subjects were uncovered, and their waveform changes throughout the movie were quantified. The long-latency (85-175 ms) parts of the responses were modulated in concordance with the participants' average moment-by-moment ratings of own engagement in the haptic content of the movie (correlation r = 0.49; ratings collected after the MEG session). The results, obtained by using novel signal-analysis approaches, demonstrate that the functional state of the human sensorimotor cortex fluctuates in a fine-grained manner even during passive observation of temporally varying haptic events. Hum Brain Mapp 37:4061-4068, 2016. (c) 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID- 27364186 TI - SPECT/CT lymphogammagraphy of a contralateral axillary drainage in a patient with breast cancer. PMID- 27364187 TI - Magnetic domain wall tweezers: a new tool for mechanobiology studies on individual target cells. AB - In vitro tests are of fundamental importance for investigating cell mechanisms in response to mechanical stimuli or the impact of the genotype on cell mechanical properties. In particular, the application of controlled forces to activate specific bio-pathways and investigate their effects, mimicking the role of the cellular environment, is becoming a prominent approach in the emerging field of mechanobiology. Here, we present an on-chip device based on magnetic domain wall manipulators, which allows the application of finely controlled and localized forces on target living cells. In particular, we demonstrate the application of a magnetic force in the order of hundreds of pN on the membrane of HeLa cells cultured on-chip, via manipulation of 1 MUm superparamagnetic beads. Such a mechanical stimulus produces a sizable local indentation of the cellular membrane of about 2 MUm. Upon evaluation of the beads' position within the magnetic field originated by the domain wall, the force applied during the experiments is accurately quantified via micromagnetic simulations. The obtained value is in good agreement with that calculated by the application of an elastic model to the cellular membrane. PMID- 27364188 TI - Check the guide wire after catheter placement. PMID- 27364189 TI - Potential role of costimulatory pathways in immune dysfunction in hemodialysis patients. PMID- 27364191 TI - The effects of shear and particle shape on the physical adsorption of polyvinyl pyrrolidone on carbon nanoparticles. AB - The effects of shear and particle shape on the physical adsorption of a polymer (polyvinyl pyrrolidone, PVP) on carbon nanoparticles (CNPs) were studied with dissipative particle dynamics (DPD) methods. It was found that the conformation of the polymer during adsorption and desorption from the nanoparticle can be classified into three possible types, i.e. adsorbed, shear-affected and separated, depending on the magnitude of the shear rate in the flow. Spherical and graphene sheet-shaped particles with adsorbed PVP were manipulated in a Couette flow to determine the threshold shear rates leading to changes in the polymer adsorption state. It was found that the polymer was stably adsorbed under higher shear conditions for graphene sheets. In addition, the end-to-end distance and the radius of gyration of the polymer adsorbate was clearly related to the adsorption state, as the polymer underwent a transition from adsorbed to the separated state when the shear rate increased. The critical shear rate at which the polymer desorbed from the surface could be useful in applications where nanoparticles can be used as a molecular delivery system. The physical adsorption and desorption of the same polymer molecules on a flat surface were also investigated. The desorption of the polymer from the flat surface occurred when the shearing force was stronger than the attraction between the PVP and the surface. PMID- 27364190 TI - Computational exploration of the binding mode of heme-dependent stimulators into the active catalytic domain of soluble guanylate cyclase. AB - Soluble guanylate cyclase (sGC), the main target of nitric oxide (NO), has been proven to have a significant role in coronary artery disease, pulmonary hypertension, erectile dysfunction, and myocardial infarction. One of its agonists, BAY 41-2272 (Riociguat), has been recently approved for treatment of pulmonary arterial hypertension (PHA), while some others are in clinical phases of development. However, the location of the binding sites for the two known types of agonists, heme-dependent stimulators and heme-independent activators, is a matter of debate, particularly for the first group where both a location on the regulatory (H-NOX) and on the catalytic domain have been suggested by different authors. Here, we address its potential location on the catalytic domain, the unique well characterized at the structural level, by an "in silico" approach. Homology models of the catalytic domain of sGC in "inactive" or "active" conformations were constructed using the structure of previously described crystals of the catalytic domains of "inactive" sGCs (2WZ1, 3ET6) and of "active" adenylate cyclase (1CJU). Each model was submitted to six independent molecular dynamics simulations of about 1 MUs. Docking of YC-1, a classic heme-dependent stimulator, to all frames of representative trajectories of "inactive" and "active" conformations, followed by calculation of absolute binding free energies with the linear interaction energy (LIE) method, revealed a potential high affinity binding site on the "active" structure. The site, located between the pseudo-symmetric and the catalytic site just over the loop beta2 -beta3 , does not overlap with the forskolin binding site on adenylate cyclases. Proteins 2016; 84:1534-1548. (c) 2016 Wiley Periodicals, Inc. PMID- 27364193 TI - How ideas are spread and used. PMID- 27364192 TI - Effects of fluctuating temperature and food availability on reproduction and lifespan. AB - Experimental studies on energetics and aging often remove two major factors that in part regulate the energy budget in a normal healthy individual: reproduction and fluctuating environmental conditions that challenge homeostasis. Here we use the cyclical parthenogenetic Daphnia pulex to evaluate the role of a fluctuating thermal environment on both reproduction and lifespan across six food concentrations. We test the hypotheses that (1) caloric restriction extends lifespan; (2) maximal reproduction will come with a cost of shortened lifespan; and (3) at a given food concentration, relative to a metabolically equivalent constant temperature environment a diel fluctuating thermal environment will alter the allocation of energy to reproduction and lifespan to maintain homeostasis. We did not identify a level of food concentration that extended lifespan in response to caloric restriction, and we found no cost of reproduction in terms of lifespan. Rather, the individuals at the highest food levels generally had the highest reproductive output and the longest lifespans, the individuals at the intermediate food level decreased reproduction and maintained lifespan, and the individuals at the three lower food concentrations had a decrease in reproduction and lifespan as would be predicted with increasing levels of starvation. Fluctuating temperature had no effect on lifespan at any food concentration, but delayed time to reproductive maturity and decreased early reproductive output at all food concentrations. This suggests that a fluctuating temperature regimen activates molecular pathways that alter energy allocation. The costs of fluctuating temperature on reproduction were not consistent across the lifespan. Statistical interactions for age of peak reproduction and lifetime fecundity suggest that senescence of the reproductive system may vary between temperature regimens at the different food concentrations. PMID- 27364194 TI - Authors' response. PMID- 27364195 TI - Miniscrew anchorage. PMID- 27364196 TI - Dental maturation is not a reliable indicator of the pubertal growth spurt. PMID- 27364197 TI - Authors' response. PMID- 27364198 TI - Validity of the CVM method to determine mandibular length. PMID- 27364199 TI - Authors' response. PMID- 27364200 TI - Posttreatment evaluation of maxillary canine positions in 15-year-old subjects. PMID- 27364202 TI - Well begun, half done. PMID- 27364203 TI - Comparative effectiveness of pharmacologic and nonpharmacologic interventions for orthodontic pain relief at peak pain intensity: A Bayesian network meta-analysis. AB - INTRODUCTION: The objective of this network meta-analysis was to synthesize the evidence of the comparative effectiveness for various interventions used for orthodontic pain relief during peak pain intensity. METHODS: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched to December 31, 2014, to identify relevant studies. Additional studies were found by hand searching of journals and reference lists. Unpublished articles were also searched. Eligible studies were randomized controlled trials evaluating the effectiveness of pharmacologic or nonpharmacologic interventions for pain relief after placement of separators or an initial aligning archwire. A covariate adjusted arm-based 3-level hierarchical Bayesian random-effects model was used for this network meta-analysis. RESULTS: Twenty-four randomized controlled trials (2273 participants; 997 male, 1276 female; mean age, 18.2 years; SD, 4.4 years) were included in this network meta-analysis. A total of 26 interventions were identified and classified into 6 classes based on their mechanism of action. Compared with placebo-class, nonsteroidal anti-inflammatory drug analgesics and lasers were the most effective intervention classes with a shared median rank of 2 (95% credible interval [CrI], 1-3), followed by "other" analgesics (median rank, 3; 95% CrI, 1-4), behavior therapy (median rank, 4; 95% CrI, 3-6), and miscellaneous (median rank, 5; 95% CrI 3-6). The most effective individual interventions in the nonsteroidal anti-inflammatory drug analgesics and lasers classes were etoricoxib (median rank, 1; 95% CrI, 1-3) and gallium-arsenide superpulsed lasers (median rank, 3; 95% CrI, 1-13), respectively. Assessment of transitivity and consistency assumption showed no threat to the network meta analysis estimates. There was no evidence of significant publication bias. Heterogeneity was mild to moderate (tau-square, 0.044; 95% CrI, 0.040-0.055). CONCLUSIONS: The results show that analgesics and lasers are effective in the management of orthodontic pain at its peak intensity. Further research is required to improve the quality of evidence, especially for analgesic interventions. PMID- 27364204 TI - Effectiveness of biologic methods of inhibiting orthodontic tooth movement in animal studies. AB - INTRODUCTION: A number of biologic methods leading to decreased rates of orthodontic tooth movement (OTM) can be found in the recent literature. The aim of this systematic review was to provide an overview of biologic methods and their effects on OTM inhibition. METHODS: An electronic search was performed up to January 2016. Two researchers independently selected the studies (kappa index, 0.8) using the selection criteria established in the PRISMA statement. The methodologic quality of the articles was assessed objectively according to the Methodological Index for Non-Randomized Studies scale. RESULTS: We retrieved 861 articles in the initial electronic search, and 57 were finally analyzed. Three biologic techniques were identified as reducing the rate of OTM: chemical methods, low-level laser therapy, and gene therapy. When the experimental objective was to slow down OTM, pharmacologic modulation was the most frequently described method (53 articles). Rats were the most frequent model (38 of 57 articles), followed by mice (9 of 57), rabbits (4 of 57), guinea pigs (2 of 57), dogs (2 of 57), cats (1 of 57), and monkeys (1 of 57). The sample sizes seldom exceeded 25 subjects per group (6 of 57 articles). The application protocols, quality, and effectiveness of the different biologic methods in reducing OTM varied widely. CONCLUSIONS: OTM inhibition was experimentally tested with various biologic methods that were notably effective at bench scale, although their clinical applicability to humans was rarely tested further. Rigorous randomized clinical trials are therefore needed to allow the orthodontist to improve the effect of translating them from bench to clinic. PMID- 27364205 TI - Qualitative evaluation of pretreatment patient concerns in orthodontics. AB - INTRODUCTION: A discrepancy exists between objective and subjective measures of orthodontic treatment need, highlighting the importance of patients' perceptions. Limited qualitative information is available regarding patients' perceptions and orthodontic concerns. For the first time, patient facial images and qualitative methodology were used to assess patients' orthodontic concerns, which are incorporated into and are important in treatment planning and consent. METHODS: An interview-based, cross-sectional study of adolescent patients eligible to receive orthodontic treatment in a public dental hospital was conducted with 105 adolescents (42 boys, 63 girls) aged between 12 and 17 years. Each patient's face was video recorded, and 3 images were selected from each recording to assess the patient's orthodontic concerns. The initial chief concerns were compared with concerns articulated after the patients assessed their facial images. In addition, patient concerns were compared with occlusal features visible on smiling using the Dental Aesthetic Index and patient study casts. RESULTS: For 37% of the adolescent patients, smiling images helped to identify additional concerns. For 87%, their smiling images helped them to describe their concerns in more detail. In addition, a few patients did not articulate any concern about features measurable on the Dental Aesthetic Index that were visible on smiling. CONCLUSIONS: Showing adolescent patients images of their face and smile helped them to identify and better describe their concerns. Adolescents are not always overly concerned about visible and quantifiable malocclusion features. This might influence orthodontic treatment planning and consent. PMID- 27364207 TI - Three-dimensional photographs for determining the Index of Orthodontic Treatment Need in scientific studies. AB - INTRODUCTION: Plaster casts as the medium for data collection in orthodontic studies pose disadvantages. In this study, we aimed to assess the validity and reliability of using 3-dimensional (3D) photographs instead of plaster casts to determine the Index of Orthodontic Treatment Need (IOTN) score. METHODS: Data were collected retrospectively from the clinical records of 91 subjects. The IOTN grades were independently determined first from plaster casts, then from 2 dimensional (2D) and 3D photographs only, and then from 2D and 3D photographs combined with radiographs. IOTN grade agreement was assessed using kappa statistics and percentages of agreement. RESULTS: The percentages of agreement between both photographic sets and the plaster casts varied among the different occlusal traits from 63.7% to 93.4%. Agreement between the IOTN grades obtained from 2D and 3D photographs only and the IOTN grades obtained from plaster casts was fair (K = 0.35). The reliability of using 2D and 3D photographs instead of plaster casts was improved when those were combined with radiographs. CONCLUSIONS: In general terms, orthodontic treatment need can be assessed from 2D and 3D pictures; however, the individual occlusal traits are sufficiently assessed only when these pictures are combined with radiographs. Plaster casts remain the preferred method compared with 3D pictures for assessment of the IOTN. PMID- 27364206 TI - Association between malocclusion and the contextual factors of quality of life and socioeconomic status. AB - INTRODUCTION: The purpose of this study was to examine associations among malocclusion and the contextual factors of quality of life and socioeconomic status. METHODS: A cross-sectional study was conducted with a population-based sample of 1256 children from 7 to 10 years old. Malocclusion was assessed clinically; oral health-related quality of life (OHRQoL) was assessed using the Brazilian version of the child perceptions questionnaire; socioeconomic status was determined from data made available by the Research and Planning Institute of Piracicaba, Sao Paulo, Brazil. Initially, bivariate analyses were performed; after this, starting with variables with P <=0.20, multilevel multiple logistic regression models were estimated, in which the binomial distribution, function of the logistic connection, and criteria for remaining in the model at P <=0.05 were considered. RESULTS: Of the children, 82.1% had some type of malocclusion. Increased age associated with low socioeconomic status was the determinant for occlusal problems. The determination of low OHRQoL appears to be associated with the socioeconomic status in the individual factors, and increased overjet appears to be associated with factors at the contextual level. CONCLUSIONS: Socioeconomic status and age are risk factors for malocclusion. Of the malocclusions evaluated, increased overjet had the most negative influence on the OHRQoL. PMID- 27364208 TI - Posterior tooth angulations in patients with anterior open bite and normal occlusion. AB - INTRODUCTION: The aim of this study was to compare the posterior tooth angulations in patients with open-bite malocclusion and normal occlusion. METHODS: Lateral cephalometric headfilms of 45 untreated open-bite subjects were compared with the lateral headfilms of 45 subjects with normal occlusion in the permanent dentition. The groups were matched for age and sex distribution and compared with t tests. RESULTS: The maxillary and mandibular premolars were more mesially angulated in relation to the bisected occlusal plane, and the first and second molars were significantly more distally angulated in the open-bite group in relation to the palatal and mandibular planes. CONCLUSIONS: The maxillary and mandibular premolars were more mesially angulated in relation to the bisected occlusal plane and therefore do not compensate for the divergence of the palatal and mandibular planes as the molars do. PMID- 27364209 TI - Evaluation of long-term stability of skeletal anterior open bite correction in adults treated with maxillary posterior segment intrusion using zygomatic miniplates. AB - INTRODUCTION: This study evaluated the long-term stability of maxillary molar intrusion and anterior open-bite correction in adults treated by maxillary posterior teeth intrusion with zygomatic miniplates. METHODS: The sample included 26 skeletal anterior open-bite patients, who had maxillary posterior segment intrusion with zygomatic miniplates. Lateral cephalograms were taken at pretreatment, posttreatment, 1 year posttreatment, and 4 years posttreatment. RESULTS: The mean maxillary molar intrusion was 3.04 mm (P <=0.01), and the mean bite closure was 6.93 mm (P <=0.01). The intruded maxillary molars relapsed by 10.20% in the first year after treatment and by 13.37% by 4 years after treatment. Overbite relapsed by 8.19% and 11.18% after 1 year and 4 years posttreatment, respectively. The first year after treatment accounted for 76.29% and 73.2% of the total relapses of molar intrusion and overbite, respectively. The 4-year posttreatment relapse amounts of maxillary molar intrusion and overbite were positively correlated with the amount of pretreatment maxillary molar height and the initial open-bite severity, respectively, but negatively correlated with the amounts of maxillary molar intrusion and open-bite correction gained by treatment. CONCLUSIONS: Molar intrusion with zygomatic miniplates appears to be stable 4 years after treatment. PMID- 27364210 TI - Surface analysis of 2 orthodontic mini-implants after clinical use. AB - INTRODUCTION: The purpose of this study was to analyze the design and surface morphology of 2 brands of mini-implants before and after 12 to 18 months of clinical use. METHODS: We studied 22 mini-implants sold in the Brazilian market by 2 companies (Forestadent, Pforzheim, Germany; and Dental Morelli, Sorocaba, Sao Paulo, Brazil). The surface morphology of the mini-implants was analyzed by scanning electron microscopy before and after insertion in the oral environment to aid orthodontic movement. RESULTS: The Forestadent and the Morelli mini implants showed different shapes (size, screw thread design), and the surface morphology changed after clinical use. The most important surface morphology alterations after clinical use were strain in several parts and fracture of the active thread part of some mini-implants. CONCLUSIONS: The results of the analyses showed that the screw threads of the mini-implants differ in pitch, angle, and length. The mini-implants also showed differences in body design, active tip, and taper. These differences affect the performance of the mini implants. After clinical use, all mini-implants showed surface degradation, plastic deformation, and some fractures. PMID- 27364211 TI - Reliability of cervical vertebral maturation staging. AB - INTRODUCTION: Growth and its prediction are important for the success of many orthodontic treatments. The aim of this study was to determine the reliability of the cervical vertebral maturation (CVM) method for the assessment of mandibular growth. METHODS: A group of 20 orthodontic clinicians, inexperienced in CVM staging, was trained to use the improved version of the CVM method for the assessment of mandibular growth with a teaching program. They independently assessed 72 consecutive lateral cephalograms, taken at Liverpool University Dental Hospital, on 2 occasions. The cephalograms were presented in 2 different random orders and interspersed with 11 additional images for standardization. The intraobserver and interobserver agreement values were evaluated using the weighted kappa statistic. RESULTS: The intraobserver and interobserver agreement values were substantial (weighted kappa, 0.6-0.8). The overall intraobserver agreement was 0.70 (SE, 0.01), with average agreement of 89%. The interobserver agreement values were 0.68 (SE, 0.03) for phase 1 and 0.66 (SE, 0.03) for phase 2, with average interobserver agreement of 88%. CONCLUSIONS: The intraobserver and interobserver agreement values of classifying the vertebral stages with the CVM method were substantial. These findings demonstrate that this method of CVM classification is reproducible and reliable. PMID- 27364212 TI - Preliminary biometric analysis of mesiodistal tooth dimensions in subjects with normal occlusion. AB - INTRODUCTION: The aims of this study were to confirm the efficacy of the Bolton index in a group of natural Class I white Italian patients with complete dentition, minimal crowding, and no previous orthodontic treatment, and to evaluate the mesiodistal tooth dimensions with multivariate cluster analysis. METHODS: Tooth measurements were obtained from a sample of 56 patients with normal occlusion, with a normal Bolton index (22 men, 34 women; mean age, 27.8 years), without previous orthodontic treatment or prosthetic or Class II restorations. Maxillary and mandibular measurements were analyzed separately in the sexes. Clustering was performed using the partitioning around medoid algorithm and principal component analysis-based transformed data. Statistical analysis was conducted. RESULTS: The multivariate analysis showed 3 distinct clusters of both maxillary and mandibular tooth measurements in the male and female subjects. Statistically significant differences were found between the sexes in terms of average tooth measurements, and there was significant proportionality between the maxillary and mandibular arch clusters. CONCLUSION: Although the Bolton index is useful for identifying dentodental discrepancies in most patients, cluster analysis enabled the mandibular and maxillary tooth dimensions of the male and female subjects to be divided into 3 general classes (clusters) and the precise location of the discrepancies to be pinpointed. PMID- 27364213 TI - Malocclusion and its relationship to speech sound production: Redefining the effect of malocclusal traits on sound production. AB - INTRODUCTION: The purpose of this study was to identify variables of dental malocclusion with the greatest effect on sound production that can be easily identified during an orthodontic assessment. METHODS: One hundred fifteen patients (8.2-36 years of age) seeking orthodontic evaluation were assessed for speech sound production abnormalities. An orthodontic clinical examination assessed Angle classification, overjet, overbite, crowding, spacing, and crossbites. A standard speech sample was elicited from each subject. RESULTS: The results indicated that 71 (62%) of the subjects made a production error, particularly with the /s/ and /t/ sounds. However, auditory distortions occurred in 12 subjects (20%), and 56 (80%) subjects had visual distortions of the sound. An open bite (>2 mm) was the key malocclusal factor underlying speech sound errors. There was statistical significance between the Orthodontic Treatment Priority Index and the sound errors of /s / and /t/ (mean score of 9.54 vs 6.29 for subjects without sound errors). CONCLUSIONS: Predictive malocclusal traits are associated with speech sound production errors. The more severe or handicapping the malocclusion, the more likely that a speech sound error will occur. Open bites of 2 mm are associated with sound production errors. Visual inaccuracy of the sound occurs with more frequency than auditory inaccuracy and is the most common articulation error noted with occlusal irregularities. PMID- 27364214 TI - Are assessments of damping capacity and placement torque useful in estimating root proximity of orthodontic anchor screws? AB - INTRODUCTION: Placement torque and damping capacity may increase when the orthodontic anchor screws make contact with an adjacent root. If this is the case, root contact can be inferred from the placement torque and damping capacity. The purpose of this study was to verify the detectability of root proximity of the screws by placement torque and damping capacity. For this purpose, we investigated the relationship among placement torque, damping capacity, and screw-root proximity. METHODS: The placement torque, damping capacity, and root proximity of 202 screws (diameter, 1.6 mm; length, 8.0 mm) were evaluated in 110 patients (31 male, 79 female; mean age, 21.3 +/- 6.9 years). Placement torque was measured using a digital torque tester, damping capacity was measured with a Periotest device (Medizintechnik Gulden, Modautal, Germany), and root contact was judged using cone-beam computed tomography images. RESULTS: The rate of root contact was 18.3%. Placement torque and damping capacity were 7.8 N.cm and 3.8, respectively. The placement torque of screws with root contact was greater than that of screws with no root contact (P <0.05; effect size, 0.44; power, <0.8). Damping capacity of screws with root contact was significantly greater than that of screws with no root contact (P <0.01; effect size, >0.5; power, >0.95). CONCLUSIONS: It was suggested that the damping capacity is related to root contact. PMID- 27364215 TI - Comparison of cone-beam computed tomography with multislice computed tomography in detection of small osseous condylar defects. AB - INTRODUCTION: Previous studies have indicated that orthodontic-grade cone-beam computed tomography (CBCT) images are limited when displaying small defects at the mandibular condyles for diagnosis. In this study, we investigated whether this limitation was inherent to CBCT by comparing CBCT with multislice computed tomography (CT), and whether image segmentation and color mapping could overcome this limitation. METHODS: Nine fresh pig heads (18 condyles, 36 medial and lateral condylar regions) were used. Small osseous defects (diameter and depth, 1.5 mm) were created at the medial and lateral regions of the condyles shown by gutta percha markers. After the overlying soft tissues were restored, the pig heads underwent orthodontic-grade CBCT scans (0.4-mm voxel size; i-CAT; Imaging Sciences International, Hatfield, Pa) and medical-grade CT scans (0.625-mm voxel size; LightSpeed; GE, Little Chalfont, Buckinghamshire, United Kingdom). Subsequently, 2 calibrated and blinded raters diagnosed the defect numbers in each condylar region from CBCT and CT images using Dolphin 3D software (Patterson Supply, St Paul, Minn) without image segmentation, and then 1 week later with the proprietary image segmentation and color mapping tools of Dolphin 3D. Condylar polyvinyl siloxane impressions were collected and evaluated by the same raters to obtain physical diagnoses. Rediagnoses were made on randomly selected subsamples to assess reliability. Using the physical diagnoses as references, the accuracy of imaging diagnosis was assessed and statistically compared among the varied imaging and analysis methods. RESULTS: Image diagnoses of all imaging and analysis methods showed good or excellent intrarater and interrater reliability values, except for those of the segmented CBCT images, which were substantially lower. The numbers of overdiagnoses and underdiagnoses per condylar region were not significantly different among the varied imaging and analysis methods (Wilcoxon tests, P >0.05), but classification functions demonstrated substantially lower sensitivity and accuracy with CBCT than with CT. Logistic regression also showed that CT had a significantly higher probability (odds ratio, 2.4) than CBCT in reaching the correct diagnosis, whereas use of the image segmentation and color mapping tool proprietary to Dolphin 3D did not improve the diagnostic accuracy from CBCT images. CONCLUSIONS: Even at a lower voxel size than medical CT images, orthodontic-grade CBCT images of mandibular condyles may be inherently less reliable and less accurate for the diagnosis of small condylar defects. PMID- 27364216 TI - Relationship of maxillary 3-dimensional posterior occlusal plane to mandibular spatial position and morphology. AB - INTRODUCTION: The purpose of this study was to examine the relationship of the 3 dimensional (3D) posterior occlusal plane (POP) and the mandibular 3D spatial position. The relationship of the POP to mandibular morphology was also investigated. METHODS: Retrospective data from a convenience sample of pretreatment diagnostic cone-beam computed tomography scans were rendered using InVivo software (Anatomage, San Jose, Calif). The sample consisted of 111 subjects (51 male, 60 female) and included growing and nongrowing subjects of different races and ethnicities. The 3D maxillary POP was defined by selecting the cusp tips of the second premolars and the second molars on the rendered images of the subjects. The angles made by this plane, in reference to the Frankfort horizontal plane, were measured against variables that described the mandibular position in the coronal, sagittal, and axial views. The POP was also compared with bilateral variables that described mandibular morphology. RESULTS: There were significant differences of the POP among the different skeletal malocclusions (P <0.0001). The POP showed significant correlations with mandibular position in the sagittal (P <0.0001), coronal (P <0.05), and axial (P <0.05) planes. The POP also showed a significant correlation with mandibular morphology (P <0.0001). CONCLUSIONS: These findings suggest that there is a distinct and significant relationship between the 3D POP and the mandibular spatial position and its morphology. PMID- 27364217 TI - Severe Class II Division 1 malocclusion in an adolescent patient, treated with a novel sagittal-guidance Twin-block appliance. AB - Class II malocclusion is a challenging anomaly in orthodontic practice. Various types of functional appliances are used to correct Class II skeletal and occlusal disharmonies in growing patients, including the Twin-block. We used a modified sagittal-guidance Twin-block appliance combined with a fixed appliance and microimplant anchorage to treat a 13-year-old Chinese boy with a severe skeletal Class II malocclusion and mandibular retrognathia. Normal overjet and a Class I molar relationship were achieved because of the advancement of mandibular development, the restriction of maxillary growth, and dentoalveolar modifications in both the maxilla and the mandible. Favorable skeletal, dental, and soft tissue relationships were accomplished after 24 months of treatment. After 2 years of retention, the results remained stable. PMID- 27364218 TI - Orthodontic treatment of a patient with unilateral orofacial muscle dysfunction: The efficacy of myofunctional therapy on the treatment outcome. AB - The orofacial muscle is an important factor in the harmony of the occlusion, and its dysfunction significantly influences a patient's occlusion after craniofacial growth and development. In this case report, we describe the successful orthodontic treatment of a patient with unilateral orofacial muscle dysfunction. A boy, 10 years 0 months of age, with a chief complaint of anterior open bite, was diagnosed with a Class III malocclusion with facial musculoskeletal asymmetry. His maxillomandibular relationships were unstable, and he was unable to lift the right corner of his mouth upon smiling because of weak right orofacial muscles. A satisfactory occlusion and a balanced smile were achieved after orthodontic treatment combined with orofacial myofunctional therapy, including muscle exercises. An acceptable occlusion and facial proportion were maintained after a 2-year retention period. These results suggest that orthodontic treatment with orofacial myofunctional therapy is an effective option for a patient with orofacial muscle dysfunction. PMID- 27364219 TI - Conservative orthodontic fixed appliance management of pediatric mandibular bilateral condylar fracture. AB - INTRODUCTION: Management of mandibular condylar fractures is difficult in children with their inherently dynamic and unstable deciduous and mixed dentitions. We present a variation of the conservative fixed orthodontic approach that was used as an adjunct to aid in the reduction of a bilateral condylar fracture in a pediatric patient. METHODS: A boy, aged 10 years 9 months, came with clinical signs and symptoms of mandibular fracture after being involved in a motor vehicle accident. A computed tomography scan showed a vertical fracture on the left condylar head, a displaced fracture of the right condylar neck, and a mandibular symphysis fracture. The patient was treated with an orthodontic fixed appliance instead of an arch bar splint, followed by elastic traction to achieve a proper occlusion and condylar remodeling. Follow-up appointments were made 2 weeks and 1, 2, 20, 37, and 49 months after treatment. RESULTS: Clinical recovery was observed 2 months after treatment. At the follow-up appointments at 20, 37, and 49 months, jaw function and occlusal relationship remained stable, and no ankylosis was observed. The computed tomography scans showed that the right condyle had remodeled, and the left condyle exhibited a slight curve in the head at 49 months posttreatment. The patient's satisfaction with these treatment results was high. CONCLUSIONS: Conservative treatment of a mandibular fracture by fixed orthodontic means is a viable treatment option that is relatively straightforward and cost-effective and has a high level of patient acceptance and comfort. PMID- 27364221 TI - Loose lips. PMID- 27364220 TI - Three-dimensional analysis of tooth movements after palatal miniscrew-supported molar distalization. AB - INTRODUCTION: The aim of this prospective clinical study was to evaluate the dentoalveolar effects of a palatal miniscrew-supported molar distalization appliance using a 3-dimensional reverse engineering method. METHODS: This study sample comprised 21 patients at an average age of 13.6 years with a bilateral Class II molar relationship. Distalization was performed using skeletal anchorage. Dental casts were obtained just before treatment and after appliance removal, and they were scanned with a 3-dimensional dental scanner. The digital dental cast images were aligned. Four points and 2 lines were determined on each tooth, and the correlations between tooth movements and the linear and angular changes were analyzed 3 dimensionally. RESULTS: In the sagittal direction, the first molars showed a mean linear movement of 4.10 +/- 1.57 mm, with distal tipping of 11.02 degrees ; the central incisors showed a mean distal movement of 0.95 +/- 0.40 mm, with retroclination of 1.59 +/- 0.59 degrees . In the vertical direction, only the first molars showed intrusion, with a mean value of -0.59 +/- 0.50 mm. Rotation of the first molars was 4.92 degrees +/- 3.09 degrees . The second molars had the greatest rotation. The highest correlation among tooth movements was found between the first and second molars. CONCLUSIONS: Through support from the anterior palatal region, the maxillary first molars were distalized without anchorage loss. Furthermore, movement was observed in all 3 planes of space with reduction from the posterior to the anterior in the maxillary arch. PMID- 27364222 TI - Analysis of covariance. PMID- 27364223 TI - Nutritional status as a predictor of duration of mechanical ventilation in critically ill children. AB - OBJECTIVES: Critically ill children admitted to the pediatric intensive care unit (PICU) often are malnourished. The aim of this study was to determine the role of nutritional status on admission as a predictor of the duration of mechanical ventilation in critically ill children. METHODS: This was a single-center, prospective cohort study, including consecutive children (ages 1 mo to 15 y) admitted to a PICU. Demographic characteristics, clinical characteristics, and nutritional status were recorded and patients were followed up until hospital discharge. Nutritional status was evaluated by anthropometric parameters and malnutrition was considered if the Z-scores for the parameters were <=-2. Adjusted Cox's regression analysis was used to determine the association between nutritional status and duration of mechanical ventilation. RESULTS: In all, 72 patients were included. The prevalence of malnutrition was 41.2%, according to height-for-age Z-score, 18.6% according to weight-for-height Z-score, and 22.1% according body mass index-for-age Z-score. Anthropometrical parameters that predicted the duration of mechanical ventilation were weight-for-age (hazard ratio [HR], 2.73; 95% confidence interval [CI], 1.44-5.18); height-for-age (HR, 2.49; 95% CI, 1.44-4.28); and upper arm muscle area-for-age (HR, 5.22; 95% CI, 1.19-22.76). CONCLUSION: Malnutrition, based on a variety of anthropometric variables, was associated with the duration of mechanical ventilation in this cohort of critically ill children. Assessment of nutritional status by anthropometry should be performed on admission to the PICU to allow targeted nutritional rehabilitation for the subset of children with existing malnutrition. PMID- 27364224 TI - Brain-derived neurotrophic factor of the cerebral microvasculature: a forgotten and nitric oxide-dependent contributor of brain-derived neurotrophic factor in the brain. AB - AIM: Evidence that brain-derived neurotrophic factor (BDNF), a neurotrophin largely involved in cognition, is expressed by cerebral endothelial cells led us to explore in rats the contribution of the cerebral microvasculature to BDNF found in brain tissue and the link between cerebrovascular nitric oxide (NO) and BDNF production. METHODS: Brain BDNF protein levels were measured before and after in situ removal of the cerebral endothelium that was achieved by brain perfusion with a 0.2% CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propane sulphonate) solution. BDNF protein and mRNA levels as well as levels of endothelial NO synthase phosphorylated at serine 1177 (P-eNOSser1177 ) were measured in cerebral microvessel-enriched fractions. These fractions were also exposed to glycerol trinitrate. Hypertension (spontaneously hypertensive rats) and physical exercise training were used as experimental approaches to modulate cerebrovascular endothelial NO production. RESULTS: CHAPS perfusion resulted in a marked decrease in brain BDNF levels. Hypertension decreased and exercise increased P-eNOSser1177 and BDNF protein levels. However, BDNF mRNA levels that were increased by exercise did not change after hypertension. Finally, in vitro exposure of cerebral microvessel-enriched fractions to glycerol trinitrate enhanced BDNF production. CONCLUSION: These data reveal that BDNF levels measured in brain homogenates correspond for a large part to BDNF present in cerebral endothelial cells and that cerebrovascular BDNF production is dependent on cerebrovascular endothelial eNOS activity. They provide a paradigm shift in the cellular source of brain BDNF and suggest a new approach to improve our understanding of the link between endothelial function and cognition. PMID- 27364225 TI - Microbiota and Alcoholic Liver Disease. PMID- 27364227 TI - Surrogate MRI markers for hyperthermia-induced release of doxorubicin from thermosensitive liposomes in tumors. AB - The efficacy of systemically applied, classical anti-cancer drugs is limited by insufficient selectivity to the tumor and the applicable dose is limited by side effects. Efficacy could be further improved by targeting of the drug to the tumor. Using thermosensitive liposomes (TSL) as a drug carrier, targeting is achieved by control of temperature in the target volume. In such an approach, effective local hyperthermia (40-43 degrees C) (HT) of the tumor is considered essential but technically challenging. Thus, visualization of local heating and drug release using TSL is considered an important tool for further improvement. Visualization and feasibility of chemodosimetry by magnetic resonance imaging (MRI) has previously been demonstrated using TSL encapsulating both, contrast agent (CA) and doxorubicin (DOX) simultaneously in the same TSL. Dosimetry has been facilitated using T1-relaxation time change as a surrogate marker for DOX deposition in the tumor. To allow higher loading of the TSL and to simplify clinical development of new TSL formulations a new approach using a mixture of TSL either loaded with DOX or MRI-CA is suggested. This was successfully tested using phosphatidyldiglycerol-based TSL (DPPG2-TSL) in Brown Norway rats with syngeneic soft tissue sarcomas (BN175) implanted at both hind legs. After intravenous application of DOX-TSL and CA-TSL, heating of one tumor above 40 degrees C for 1h using laser light resulted in highly selective DOX uptake. The DOX-concentration in the heated tumor tissue compared to the non-heated tumor showed an almost 10-fold increase. T1 and additional MRI surrogate parameters such as signal phase change were correlated to intratumoral DOX concentration. Visualization of DOX delivery in the sense of a chemodosimetry was demonstrated. Although phase-based MR-thermometry was affected by CA-TSL, phase information was found suitable for DOX concentration assessment. Local differences of DOX concentration in the tumors indicated the need for visualization of drug release for further improvement of targeting. PMID- 27364226 TI - Beyond the brain-Peripheral kisspeptin signaling is essential for promoting endometrial gland development and function. AB - Uterine growth and endometrial gland formation (adenogenesis) and function, are essential for fertility and are controlled by estrogens and other regulators, whose nature and physiological relevance are yet to be elucidated. Kisspeptin, which signals via Kiss1r, is essential for fertility, primarily through its central control of the hypothalamic-pituitary-ovarian axis, but also likely through peripheral actions. Using genetically modified mice, we addressed the contributions of central and peripheral kisspeptin signaling in regulating uterine growth and adenogenesis. Global ablation of Kiss1 or Kiss1r dramatically suppressed uterine growth and almost fully prevented adenogenesis. However, while uterine growth was fully rescued by E2 treatment of Kiss1(-/-) mice and by genetic restoration of kisspeptin signaling in GnRH neurons in Kiss1r(-/-) mice, functional adenogenesis was only marginally restored. Thus, while uterine growth is largely dependent on ovarian E2-output via central kisspeptin signaling, peripheral kisspeptin signaling is indispensable for endometrial adenogenesis and function, essential aspects of reproductive competence. PMID- 27364228 TI - Effect of aspirin in addition to oral anticoagulants in stable coronary artery disease outpatients with an indication for anticoagulation. AB - Antithrombotic management of outpatients with stable coronary artery disease (CAD) who also have an indication for long-term oral anticoagulation (OAC) is critical in daily practice, firstly because these patients are frequently seen, and secondly because they have shown a high risk of both ischemic events and bleeding as compared to patients without OAC. The current guidelines recommend that most of such patients should be treated with OAC alone (without any antiplatelet therapy) after 12 months of stability even when a stent has been implanted. Robust data are however very sparse and level of evidence very low to support such a strategy. The goal of the present manuscript is to review all available evidences to help the physician's choices in this specific context and to highlight the unsolved issues that should be addressed by new studies in the near future. PMID- 27364230 TI - The Influence of Agreeableness and Ego Depletion on Emotional Responding. AB - OBJECTIVE: Agreeable individuals report more intense withdrawal-oriented negative emotions across aversive situations. Two studies tested the hypothesis that self regulatory depletion (i.e., ego depletion) moderates the relationship between trait Agreeableness and negative emotional responding. METHOD: Ego depletion was manipulated using a writing task. Emotional responding was measured with startle eye-blink responses (Study 1, N = 71) and self-reported valence, arousal, and empathic concern (Study 2, N = 256) during emotional picture viewing. Trait Agreeableness was measured using a questionnaire. RESULTS: In Study 1, Agreeableness predicted especially large startle responses during aversive images and especially small startles during appetitive images. After exercising self control, the relationship between startle magnitudes and Agreeableness decreased. In Study 2, Agreeableness predicted more empathic concern for aversive images, which in turn predicted heightened self-reported negative emotions. After exercising self-control, the relationship between Agreeableness and empathic concern decreased. CONCLUSIONS: Agreeable individuals exhibit heightened negative emotional responding. Ego depletion reduced the link between Agreeableness and negative emotional responding in Study 1 and moderated the indirect effect of Agreeableness on negative emotional responding via empathic concern in Study 2. Empathic concern appears to be a resource-intensive process underlying heightened responding to aversive stimuli among agreeable persons. PMID- 27364229 TI - Deep tissue volume imaging of birefringence through fibre-optic needle probes for the delineation of breast tumour. AB - Identifying tumour margins during breast-conserving surgeries is a persistent challenge. We have previously developed miniature needle probes that could enable intraoperative volume imaging with optical coherence tomography. In many situations, however, scattering contrast alone is insufficient to clearly identify and delineate malignant regions. Additional polarization-sensitive measurements provide the means to assess birefringence, which is elevated in oriented collagen fibres and may offer an intrinsic biomarker to differentiate tumour from benign tissue. Here, we performed polarization-sensitive optical coherence tomography through miniature imaging needles and developed an algorithm to efficiently reconstruct images of the depth-resolved tissue birefringence free of artefacts. First ex vivo imaging of breast tumour samples revealed excellent contrast between lowly birefringent malignant regions, and stromal tissue, which is rich in oriented collagen and exhibits higher birefringence, as confirmed with co-located histology. The ability to clearly differentiate between tumour and uninvolved stroma based on intrinsic contrast could prove decisive for the intraoperative assessment of tumour margins. PMID- 27364231 TI - Back to the Future - Tapping into Ancient Grains for Food Diversity. AB - Einkorn, emmer, and spelt are old wheat species that have fed the world for centuries before they have nearly completely been replaced by modern bread wheat. Nowadays, the diversity of these old species lies frozen in gene banks and rare attempts aim to exploit them as a source for genetic diversity in modern wheat breeding. Here, we want to raise a debate on a more holistic exploitation of ancient species via their direct introduction to the consumer market as high quality products. Although exemplified only for ancient wheat species, this innovative self-financing strategy can be directly extended to other species. A central requirement for this concept is intensive communication, coordination, and interdisciplinary research along the entire production chain from farm to fork. PMID- 27364232 TI - Phasic alertness enhances processing of face and non-face stimuli in congenital prosopagnosia. AB - Congenital prosopagnosia (CP) is a severe face processing impairment that occurs in the absence of any obvious brain damage and has often been associated with a more general deficit in deriving holistic relations between facial features or even between non-face shape dimensions. Here we further characterized this deficit and examined a potential way to ameliorate it. To this end we manipulated phasic alertness using alerting cues previously shown to modulate attention and enhance global processing of visual stimuli in normal observers. Specifically, we first examined whether individuals with CP, similarly to controls, would show greater global processing when exposed to an alerting cue in the context of a non facial task (Navon global/local task). We then explored the effect of an alerting cue on face processing (upright/inverted face discrimination). Confirming previous findings, in the absence of alerting cues, controls showed a typical global bias in the Navon task and an inversion effect indexing holistic processing in the upright/inverted task, while CP failed to show these effects. Critically, when alerting cues preceded the experimental trials, both groups showed enhanced global interference and a larger inversion effect. These results suggest that phasic alertness may modulate visual processing and consequently, affect global/holistic perception. Hence, these findings further reinforce the notion that global/holistic processing may serve as a possible mechanism underlying the face processing deficit in CP. Moreover, they imply a possible route for enhancing face processing in individuals with CP and thus shed new light on potential amelioration of this disorder. PMID- 27364233 TI - Down-regulation of the glucan synthase-like 6 gene (HvGsl6) in barley leads to decreased callose accumulation and increased cell wall penetration by Blumeria graminis f. sp. hordei. AB - The recent characterization of the polysaccharide composition of papillae deposited at the barley cell wall during infection by the powdery mildew pathogen, Blumeria graminis f. sp. hordei (Bgh), has provided new targets for the generation of enhanced disease resistance. The role of callose in papilla-based penetration resistance of crop species is largely unknown because the genes involved in the observed callose accumulation have not been identified unequivocally. We have employed both comparative and functional genomics approaches to identify the functional orthologue of AtGsl5 in the barley genome. HvGsl6 (the barley glucan synthase-like 6 gene), which has the highest sequence identity to AtGsl5, is the only Bgh-induced gene among the HvGsls examined in this study. Through double-stranded RNA interference (dsRNAi)-mediated silencing of HvGsl6, we have shown that the down-regulation of HvGsl6 is associated with a lower accumulation of papillary and wound callose and a higher susceptibility to penetration of the papillae by Bgh, compared with control lines. The results indicate that the HvGsl6 gene is a functional orthologue of AtGsl5 and is involved in papillary callose accumulation in barley. The increased susceptibility of HvGsl6 dsRNAi transgenic lines to infection indicates that callose positively contributes to the barley fungal penetration resistance mechanism. PMID- 27364234 TI - Body mass index and waist circumference as predictors of all-cause mortality in an Aboriginal Australian community. AB - OBJECTIVE: Although elevated body mass index (BMI) and waist circumference (WC) have been identified as risk factors for mortality, data from the Australian Aboriginal communities are scarce. This study examined the associations of BMI and WC with all-cause mortality in an Australian Aboriginal community. METHODS: A total of 934 Aboriginal adults, aged 18-76 years, who participated in a community wide screening programme in Australia's Northern Territory from 1992 to 1998, were followed-up prospectively for up to 18 years for death outcomes. The hazard ratios for mortality were estimated by baseline BMI and WC. Age, sex, smoking and alcohol consumption status were adjusted for in multivariable analysis. RESULTS: In 14,750 person-years of follow-up, 216 deaths were recorded. For each standard deviation increase in BMI, the risk of all-cause death decreased by 9% (95% CI: 0.80-1.05); whereas for each SD increase in WC, the risk of all-cause mortality increased by 17% (95% CI: 1.03-1.33). The risk of mortality was lower in the 3rd BMI tertile compared to the 1st tertile for mortality after adjusting for WC, age, sex, smoking and alcohol consumption. Risk of death was higher in WC tertile 3 compared to tertile 1 after adjusting for BMI, age, sex, smoking and alcohol consumption. CONCLUSIONS: The risk of all-cause mortality among participants increased with higher WC, while participants with relatively higher BMI had a lower mortality risk. WC had stronger association with mortality than did BMI. The results indicate the importance of assessing WC measures in studies conducted in Aboriginal Australia. PMID- 27364235 TI - Brown adipose tissue transplantation ameliorates male fertility impairment caused by diet-induced obesity. AB - Populations with obesity or overweight have a high incidence of infertility. We hypothesised that brown adipose tissue (BAT) transplantation can attenuate the impairment of male fertility caused by diet-induced obesity. BATs were transplanted from male donor mice into age and sex matched recipient mice fed high-fat diets (HFD). Sperm motility experiment was conducted after surgical procedure. X-ray computed tomography scanning, biochemical assay, real-time PCR and western blot analysis were performed. BAT transplantation reduced body fat and epididymal fat mass, as well as triglycerides (TG) content in testis and epididymis and total cholesterol (TCHO) contents in epididymis compared with the HFD group. Sperm motility and progressiveness were recovered and mRNA and protein levels of genes related to sperm motility such as cullin 3 (Cul3), peroxisome proliferator activated receptor alpha (PPARalpha) and its down-stream genes were significantly down-regulated post BAT transplantation. BAT transplantation partially ameliorated impairment of male fertility caused by diet-induced obesity. PMID- 27364251 TI - Introduction: (In)famous neurological injuries and disease: cases and events of historical, political, cultural, and scientific impact: Part 2. PMID- 27364254 TI - Deep brain stimulation for autism spectrum disorders. PMID- 27364253 TI - Chen Jingrun, China's famous mathematician: devastated by brain injuries on the doorstep to solving a fundamental mathematical puzzle. AB - Chen Jingrun (1933-1996), perhaps the most prodigious mathematician of his time, focused on the field of analytical number theory. His work on Waring's problem, Legendre's conjecture, and Goldbach's conjecture led to progress in analytical number theory in the form of "Chen's Theorem," which he published in 1966 and 1973. His early life was ravaged by the Second Sino-Japanese War and the Chinese Cultural Revolution. On the verge of solving Goldbach's conjecture in 1984, Chen was struck by a bicyclist while also bicycling and suffered severe brain trauma. During his hospitalization, he was also found to have Parkinson's disease. Chen suffered another serious brain concussion after a fall only a few months after recovering from the bicycle crash. With significant deficits, he remained hospitalized for several years without making progress while receiving modern Western medical therapies. In 1988 traditional Chinese medicine experts were called in to assist with his treatment. After a year of acupuncture and oxygen therapy, Chen could control his basic bowel and bladder functions, he could walk slowly, and his swallowing and speech improved. When Chen was unable to produce complex work or finish his final work on Goldbach's conjecture, his mathematical pursuits were taken up vigorously by his dedicated students. He was able to publish Youth Math, a mathematics book that became an inspiration in Chinese education. Although he died in 1996 at the age of 63 after surviving brutal political repression, being deprived of neurological function at the very peak of his genius, and having to be supported by his wife, Chen ironically became a symbol of dedication, perseverance, and motivation to his students and associates, to Chinese youth, to a nation, and to mathematicians and scientists worldwide. PMID- 27364252 TI - Human prion diseases: surgical lessons learned from iatrogenic prion transmission. AB - The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood "infectious protein" has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions. Interestingly, since their discovery, there have been more than 492 incidents of iatrogenic transmission of prion diseases, largely resulting from prion-contaminated growth hormone and dura mater grafts. Although fewer than 9 cases of probable iatrogenic neurosurgical cases of Creutzfeldt-Jakob disease (CJD) have been reported worldwide, the likelihood of some missed cases and the potential for prion transmission by neurosurgery create considerable concern. Laboratory studies indicate that standard decontamination and sterilization procedures may be insufficient to completely remove infectivity from prion-contaminated instruments. In this unfortunate event, the instruments may transmit the prion disease to others. Much caution therefore should be taken in the absence of strong evidence against the presence of a prion disease in a neurosurgical patient. While the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have devised risk assessment and decontamination protocols for the prevention of iatrogenic transmission of the prion diseases, incidents of possible exposure to prions have unfortunately occurred in the United States. In this article, the authors outline the historical discoveries that led from kuru to the identification and isolation of the pathological prion proteins in addition to providing a brief description of human prion diseases and iatrogenic forms of CJD, a brief history of prion disease nosocomial transmission, and a summary of the CDC and WHO guidelines for prevention of prion disease transmission and decontamination of prion-contaminated neurosurgical instruments. PMID- 27364255 TI - Two cases of 16th century head injuries managed in royal European families. AB - In Europe, during the 16th century, there were a number of prominent general surgeons adventurous enough to consider operating on the brain for head injuries. From the time of Hippocrates, operating on the skull and brain was considered both treacherous and too dangerous to be undertaken except on rare occasions. Operating on a member of a royal court was considered even more exceptional because if the outcome was poor, the surgeon could lose a hand or limb, or, even worse, be beheaded. The authors present two interesting cases of royal family members who underwent surgery for head injuries that were quite severe. The surgeons involved, Ambroise Pare, Andreas Vesalius, and Berengario da Carpi, were among the most prominent surgeons in Europe. Despite very challenging political situations, all were willing to undertake a complex surgical intervention on the member of a prominent royal family. The individuals involved, both royal and medical, plus the neurosurgical injuries are discussed. PMID- 27364256 TI - Monsters and the case of L. Joseph: Andre Feil's thesis on the origin of the Klippel-Feil syndrome and a social transformation of medicine. AB - Andre Feil (1884-1955) was a French physician best recognized for his description, coauthored with Maurice Klippel, of patients with congenital fusion of cervical vertebrae, a condition currently known as Klippel-Feil syndrome. However, little is known about his background aside from the fact that he was a student of Klippel and a physician who took a keen interest in describing congenital anomalies. Despite the relative lack of information on Feil, his contributions to the fields of spinal disease and teratology extended far beyond science to play an integral role in changing the misguided perception shrouding patients with disfigurements, defects, deformities, and so-called monstrous births. In particular, Feil's 1919 medical school thesis on cervical abnormalities was a critical publication in defying long-held theory and opinion that human "monstrosities," anomalies, developmental abnormalities, and altered congenital physicality were a consequence of sinful behavior or a reversion to a primitive state. Indeed, his thesis on a spinal deformity centering on his patient, L. Joseph, was at the vanguard for a new view of a patient as nothing less than fully human, no matter his or her physicality or appearance. PMID- 27364257 TI - Head injury in heroes of the Civil War and its lasting influence. AB - The Civil War era was an age-defining period in the history of the United States of America, the effects of which are still seen in the nation today. In this era, the issue of head injury pervaded society. From the president of the United States, Abraham Lincoln, to the officers and soldiers of the Union and Confederate armies, and to the population at large, head injury and its ramifications gripped the nation. This article focuses on 3 individuals: Major General John Sedgwick, First Lieutenant Alonzo Cushing, and Harriet Tubman, as examples of the impact that head injury had during this era. These 3 individuals were chosen for this article because of their lasting legacies, contributions to society, and interesting connections to one another. PMID- 27364258 TI - Silas Weir Mitchell and "The Strange Case of George Dedlow". AB - It has been said of Silas Weir Mitchell (1829-1914) that as a young man he was first among the physiologists of his day, in middle age first among physicians, and as an older man, one of the most noted novelists of his country. Mitchell's novels were written in his later life as a means to avoid boredom during lengthy summer vacations that were the norm for that time among the affluent members of Philadelphia society. These novels were criticized by some because of poor plots, which in some instances failed to move along, or for text that offered a stereotyped depiction of genteel society and the effects that war or personal disaster had on the characters' behavior The criticism came despite the fact that all critics agreed that Mitchell's portrayals of psychopathology in his fictional characters was unique and accurate. However, in his 30s, Mitchell had written and by chance had published a fictional short story that not only transcended such criticisms but became immensely popular. "The Strange Case of George Dedlow" portrays a union officer who was not a physician but who had some medical background and who sustained a series of war wounds leading to severe nerve pain, the author's first description of causalgia, multiple amputations, and the psychological as well as physical symptoms of phantom limb syndrome. The protagonist tells of his torments in the first person in a very engaging fashion. Thus, long before he began writing his, at that time, acclaimed novels in the 1880s, Mitchell wrote a piece of fiction that combines accurate and very important medical observations with fiction of great historical interest. The following rendering of this now classic short story includes selected quotes and some interpretation and is perhaps appropriate for this year, 2 years after the centenary year of his death in 1914. PMID- 27364259 TI - Harvey Cushing and pituitary Case Number 3 (Mary D.): the origin of this most baffling problem in neurosurgery. AB - From the very beginning of his career, Harvey Williams Cushing (1869-1939) harbored a deep interest in a complex group of neoplasms that usually developed at the infundibulum. These were initially known as "interpeduncular" or "suprasellar" cysts. Cushing introduced the term "craniopharyngioma" for these lesions, which he believed represented one of the most baffling problems faced by neurosurgeons. The patient who most influenced Cushing's thinking was a 16-year old seamstress named "Mary D.," whom he attended in December 1901, exactly the same month that Alfred Frohlich published his seminal article describing an adiposogenital syndrome in a young boy with a pituitary cyst. Both Cushing's and Frohlich's patients showed similar symptoms caused by the same type of tumor. Notably, Cushing and Frohlich had met one another and became good friends in Liverpool the summer before these events took place. Their fortunate relationship led Cushing to realize that Frohlich's syndrome represented a state of hypopituitarism and provided a useful method of diagnosing interpeduncular cysts. It is noteworthy that Cushing's very first neurosurgical procedure on a pituitary tumor was performed in the case of Mary D.'s "interpeduncular cyst," on February 21, 1902. Cushing failed to remove this lesion, which was later found during the patient's autopsy. This case was documented as Pituitary Case Number 3 in Cushing's masterpiece, The Pituitary Body and Its Disorders, published in 1912. This tumor was considered "a teratoma"; however, multiple sources of evidence suggest that this lesion actually corresponded to an adamantinomatous craniopharyngioma. Unfortunately, the pathological specimens of this lesion were misplaced, and this prompted Cushing's decision to retain all specimens and documents of the cases he would operate on throughout his career. Accordingly, Mary D.'s case crystallized the genesis of the Cushing Brain Tumor Registry, one of Cushing's major legacies to neurosurgery. In this paper the authors analyze the case of Mary D. and the great influence it had on Cushing's conceptions of the pituitary gland and its afflictions, and on the history of pituitary surgery. PMID- 27364260 TI - The strokes that killed Churchill, Roosevelt, and Stalin. AB - From February 4 to 11, 1945, President Franklin D. Roosevelt of the United States, Soviet Union Premier Joseph Stalin, and British Prime Minister Winston Churchill met near Yalta in Crimea to discuss how post-World War II (WWII) Europe should be organized. Within 2 decades of this conference, all 3 men had died. President Roosevelt died 2 months after the Yalta Conference due to a hemorrhagic stroke. Premier Stalin died 8 years later, also due to a hemorrhagic stroke. Finally, Prime Minister Churchill died 20 years after the conference because of complications due to stroke. At the time of Yalta, these 3 men were the leaders of the most powerful countries in the world. The subsequent deterioration of their health and eventual death had varying degrees of historical significance. Churchill's illness forced him to resign as British prime minister, and the events that unfolded immediately after his resignation included Britain's mismanagement of the Egyptian Suez Crisis and also a period of mistrust with the United States. Furthermore, Roosevelt was still president and Stalin was still premier at their times of passing, so their deaths carried huge political ramifications not only for their respective countries but also for international relations. The early death of Roosevelt, in particular, may have exacerbated post WWII miscommunication between America and the Soviet Union-miscommunication that may have helped precipitate the Cold War. PMID- 27364261 TI - Field Marshal Erwin Rommel: the head injury that may have prolonged the Second World War. AB - War-related head injury, indeed neurological injury in general, has been a part of the history of humankind for as long as there has been warfare. Such injuries can result in the removal of the individual from combat, thus eliminating any subsequent contribution that he or she might have made to the battle. However, at times, the injuries can have more wide-reaching effects. In the case of commanders or leaders, the impact of their injuries may include the loss of their influence, planning, and leadership, and thus have a disproportionate effect on the battle, or indeed the war. Field Marshal Erwin Rommel was a talented military strategist and leader who was respected by friends and foes alike. He held an honored reputation by the German people and the military leadership. His head injury on July 17, 1944, resulted in his being removed from the field of battle in northern France, but also meant that he was not able to lend his stature to the assassination attempt of Adolph Hitler on July 20. It is possible that, had he been able to lend his stature to the events, Hitler's hold on the nation's government might have been loosened, and the war might have been brought to an end a year earlier. The authors review Rommel's career, his injury, the subsequent medical treatment, and his subsequent death. PMID- 27364262 TI - Beyond the game: the legacy of Bill Masterton. AB - Bill Masterton is the only man to die of injuries sustained in a National Hockey League (NHL) game. He remains the last fatality in any professional team sport involving a direct in-game injury in North America. While Masterton was originally thought to have suffered a fatal brain injury while being checked on the ice, later analysis of the case revealed evidence of second-impact syndrome and the effects of prior concussions. Masterton's death sparked both an immediate debate in the NHL on whether helmets should be compulsory and the NHL's first vote on mandatory helmet use. Although the subject of mandated helmet use met with resistance in the 10 years after Masterton's death, especially from hockey owners and coaches, the NHL finally legislated helmet use by all players entering the league beginning in the 1979-1980 season. Several awards, including one recognizing the NHL player who best exemplifies the qualities of perseverance, sportsmanship, and dedication to hockey, have been created in memory of Masterton. However, his legacy extends far beyond the awards that bear his name. His death was the seminal event bringing head safety to the forefront of a game that was both unready and unwilling to accept change. An increase in mainstream media attention in recent years has led to unprecedented public awareness of brain injury and concussion in hockey and other sports. Advances in the diagnosis and treatment of head injury in sports have occurred recently, the impetus for which started over 45 years ago, when Bill Masterton died. PMID- 27364263 TI - What to Do With Success? The Optimist's Creed in Relapsed Hodgkin Lymphoma. AB - Checkpoint inhibitors have demonstrated remarkable efficacy in patients with chemotherapy-resistant Hodgkin lymphoma. However, it remains unclear whether these impressive agents have curative potential or whether relapse and death will eventually occur. In the present review, we discuss the options for a therapeutic dilemma that is likely to occur with increasing frequency, what to do for a patient with Hodgkin lymphoma who is responding to the checkpoint inhibitors? We discuss the 4 most likely considered options: continuation of checkpoint blockade, cessation of therapy with potential retreatment, transplantation, and chimeric antigen receptor T-cell therapy. These options will require evaluation in future clinical trials; however, we propose a decision strategy that could be of use to practicing clinicians until robust data are available. PMID- 27364264 TI - Vaccination in Multiple Myeloma: Review of Current Literature. AB - Multiple myeloma is a cancer of the immune system. Infection is a major cause of morbidity and mortality in patients with multiple myeloma. Some of these infections are preventable by vaccines available to the general population. However, little is known about the clinical effectiveness of these vaccines in patients with multiple myeloma, and the cellular and humoral immune response to vaccination has not been well characterized, especially in conjunction with modern myeloma therapies. The present report reviews the basics of multiple myeloma and the immune system, the available evidence on the immunologic response of patients with multiple myeloma after vaccination, and current practice recommendations regarding specific vaccines. Understanding the immune response to vaccines could help us understand how immuno-oncology-based therapies work in multiple myeloma and provide future directions for research. PMID- 27364266 TI - Investigating Residential History Using Stable Hydrogen and Oxygen Isotopes of Human Hair and Drinking Water. AB - The relationship between isotopic signals in human hair and geographic region has potential forensic applications for identifying unknown individuals' place of recent residence. This study analyzes delta(2) H and delta(18) O isotopes in residential tap water and bulk hair samples from 17 volunteers representing 12 locations in Ontario, Canada. There is a strong correlation (R(2) = 0.9) between delta(2) H and delta(18) O values of the water samples. In contrast, the delta(2) H and delta(18) O values of the hair samples are weakly correlated (R(2) = 0.3), and the greater variability in the data is linked to dietary factors. This study demonstrates that the delta(2) H and delta(18) O values of hair and drinking water can be used to help identify potential place of residence in forensic cases, particularly in relation to proximity to large bodies of water such as the Great Lakes, but interpretations are complicated by the contribution of both water and diet to delta(2) H and delta(18) O values in hair. PMID- 27364267 TI - Ancestry Estimation in Forensic Anthropology: Geometric Morphometric versus Standard and Nonstandard Interlandmark Distances. AB - Standard cranial measurements are commonly used for ancestry estimation; however, 3D digitizers have made cranial landmark data collection and geometric morphometric (GM) analyses more popular within forensic anthropology. Yet there has been little focus on which data type works best. The goal of the present research is to test the discrimination ability of standard and nonstandard craniometric measurements and data derived from GM analysis. A total of 31 cranial landmarks were used to generate 465 interlandmark distances, including a subset of 20 commonly used measurements, and to generate principal component scores from procrustes coordinates. All were subjected to discriminant function analysis to ascertain which type of data performed best for ancestry estimation of American Black and White and Hispanic males and females. The nonstandard interlandmark distances generated the highest classification rates for females (90.5%) and males (88.2%). Using nonstandard interlandmark distances over more commonly used measurements leads to better ancestry estimates for our current population structure. PMID- 27364268 TI - DNA Profiling Success Rates from Degraded Skeletal Remains in Guatemala. AB - No data are available regarding the success of DNA Short Tandem Repeat (STR) profiling from degraded skeletal remains in Guatemala. Therefore, DNA profiling success rates relating to 2595 skeletons from eleven cases at the Forensic Anthropology Foundation of Guatemala (FAFG) are presented. The typical postmortem interval was 30 years. DNA was extracted from bone powder and amplified using Identifiler and Minifler. DNA profiling success rates differed between cases, ranging from 50.8% to 7.0%, the overall success rate for samples was 36.3%. The best DNA profiling success rates were obtained from femur (36.2%) and tooth (33.7%) samples. DNA profiles were significantly better from lower body bones than upper body bones (p = <0.0001). Bone samples from males gave significantly better profiles than samples from females (p = <0.0001). These results are believed to be related to bone density. The findings are important for designing forensic DNA sampling strategies in future victim recovery investigations. PMID- 27364269 TI - Application of mRNA Expression Analysis to Human Blood Identification in Degenerated Samples that were False-negative by Immunochromatography. AB - Forensic laboratories are often faced with cases in which methamphetamine hydrochloride-mixed blood is unable to be identified as human blood by immunochromatography against human hemoglobin A0. The application of mRNA expression analysis to samples that showed a false-negative with immunochromatography was investigated as an alternative approach that did not depend on the antigen-antibody reaction. Real-time PCR was used to examine the expression levels of blood markers such as glycophorin A, spectrin beta, and hemoglobin beta. Hemoglobin beta was the only marker that was specifically detected in blood, while glycophorin A was useful for determining human specificity. Hemoglobin beta showed good detection sensitivity and was detectable in 37-year-old blood stains. Hemoglobin beta was exclusively detectable in methamphetamine hydrochloride-mixed blood stains. Detergents and disinfectants did not significantly influence mRNA markers. The proposed mRNA expression analysis was suitable for human blood identification as an alternative method to immunochromatography. PMID- 27364270 TI - Forensic Analysis of Cigarette Ash-Brand Determination Through Trace-metal Analysis. AB - The information inherent in cigarette ash in the form of trace-metal concentrations may be of use in a forensic context as it can indicate the brand from which the ash originated. This knowledge might help place suspects at crime scenes or determine how many people may have been present. To develop and test statistical models capable of classifying ash samples according to brand, commercial cigarettes procured in the U.S. and overseas were "smoked" using a peristaltic pump, mimicking the range of human smoking habits. Ash samples were digested in a mixture of nitric and hydrochloric acid applying microwave digestion and analyzed using inductively coupled plasma-mass spectrometry. Principal component analysis of the elemental data showed intrinsic differences between brands. Partial least squares-discriminant analysis demonstrated that brand classification yields good sensitivity and specificity for a number of models tested. Varying smoking parameters did not impact the classification of ash samples. PMID- 27364271 TI - A Study of the Presence of Gunshot Residue in Pittsburgh Police Stations using SEM/EDS and LC-MS/MS. AB - Due to possible secondary transfer of gunshot residue (GSR) onto a suspect in police custody prior to sampling, a baseline must be created for the amount of GSR present. With an increase of "lead free" ammunition, testing for both gunpowder and primer GSR is relevant. Seventy samples were collected using carbon coated adhesive stubs from four Pittsburgh Police Stations and vehicles to investigate these locations as sources of secondary GSR contamination. These seventy samples were analyzed for primer GSR using scanning electron microscopy energy-dispersive X-ray spectrometry. One primer GSR particle was detected; no sample was classified as positive for primer GSR. These same samples were then analyzed for gunpowder GSR using liquid chromatography coupled to tandem mass spectrometry to test for akardite II, ethylcentralite, diphenylamine, N nitrosodiphenylamine, 2-nitrodiphenylamine, and 4-nitrodiphenylamine. Ethylcentralite was quantifiable in two test samples. These results suggest there is a negligible potential for secondary transfer of primer and gunpowder GSR. PMID- 27364272 TI - Latent Fingermark Aging Patterns (Part II): Color Contrast Between Ridges and Furrows as One Indicator of Degradation. AB - Currently, no established methodology exists to determine degradation patterns of latent fingermarks by visual means. This article is the second in a series of reports exploring quantifiable degradation-related parameters, which focuses on color contrast changes between fingermark ridges and furrows over time. Experiment variables included type of secretion (eccrine and sebaceous), substrate (glass and plastic), and exposure to natural light (dark, shade, and direct light). Fingermarks were sequentially visualized with titanium dioxide powder and photographed. Image histogram profiles were evaluated and combined with statistical analysis of color data values. Results indicate that sebaceous depositions on glass were generally less degraded by the effect of environmental conditions compared with those on plastic. In addition, aging in darkness was not always the best condition for preservation, and direct exposure to light seemed to inhibit visual degradation under certain conditions. Overall, the technique provided sufficient sensitivity to discern degradation patterns of fingermarks. PMID- 27364273 TI - Two Simple Formulas for Evaluating the Lower Bound of the Impact Velocity in Vehicle-pedestrian Accidents. AB - Formulas for evaluating the lower bound of the impact velocity are valuable in vehicle-pedestrian accident reconstruction. The theory of classical mechanics and four hypotheses were employed to derive formulas; the research results and simulation/accident tests were employed to validate their feasibility. Then, two simple formulas were developed according to the distance between the rest positions of the vehicle and the pedestrian and the flight-phase distance. The results showed that the evaluated results by the two proposed formulas are inferior to the existing results. The influence of a roadside step on the impact velocity, which decreased with an increase in the flight-phase distance and a reduction in the road slope, was evaluated. Based on a real accident, the study concludes that the lower bound can be easily obtained with the proposed formulas, which can be used to determine the evaluated impact velocity during simulations. PMID- 27364274 TI - Unintentional Nonhunting Firearm Deaths in Sweden, 1983-2012. AB - We examined the association between unintentional nonhunting firearm deaths and changes in firearm legislation in Sweden. There were 43 fatalities during the study time frame 1983-2012, representing 46% of all unintentional firearm deaths during the same period. The victims were predominantly young males (mean age 25 years). Slightly more than half of the deaths were caused by another person and were inflicted at close range. The main cause of the incidents was human error. The majority of the involved firearms were legal; however, most victims killed with illegal firearms were under the influence of alcohol and/or drugs at the time. The death rate decreased significantly following the introduction of the hunter's examination in 1985. Education and training associated with the hunter's examination was at least partially responsible for the decline in fatalities after 1985. Future prevention should target the availability of illegal firearms. PMID- 27364275 TI - Forensic Pathologist Consensus in the Interpretation of Photographs of Patterned Injuries of the Skin. AB - Forensic pathologists are commonly asked to evaluate injuries on the basis of photographs. Members of the National Association of Medical Examiners were asked to participate in an online survey in which they were presented with 68 patterned injuries of the skin and asked to make a diagnosis ranging from very general (e.g., "blunt" vs. "sharp") to specific (e.g., "baton blow"). This was not the case. Consensus for general diagnosis averaged 0.77 and 0.72 for specific diagnosis. While there was a strong correlation between consensus and confidence in aggregate, individual correlations were poor. Consensus diagnosis was inversely correlated with age, and positively correlated with jurisdictional size, medical degree, and whether or not the respondent was actively performing autopsies as a job function. A subsequent survey is exploring possible reasons for lack of consensus in low-consensus questions. The high correlation between confidence and consensus at the aggregate level and low correlation at the individual level may have implications for quality assurance protocols. PMID- 27364276 TI - The Corpus Callosum and Forensic Issues-An Overview. AB - The corpus callosum is a large central white matter tract that connects the right and left cerebral hemispheres. It permits placental mammals to have a more sophisticated interhemispheric integration of sensory cortices and allows communication between cortical and subcortical neurons. Search of the literature and the pathology archives at The University of Adelaide was undertaken to identify lesions and injuries within the corpus callosum that may have forensic significance. These include developmental/congenital lesions with agenesis/dysgenesis, vascular malformations, and lipomas; inherited syndromes such as neurofibromatosis; and acquired lesions involving trauma, neoplasia, demyelination, vascular conditions, infections, fat embolism, aging/dementia, and the effects of toxins. The finding of lesions within the corpus callosum should initiate careful examination of the adjacent brain and other organ systems for related phenomena as this may shed some light on the nature of the underlying condition, and also help to determine whether there are any forensic implications. PMID- 27364277 TI - A Study of Fatal and Nonfatal Hangings. AB - Approximately 50% of all suicides performed worldwide are strangulations. This article presents options for the medicolegal examination of hanging. The pathogenetic mechanisms and clinical pictures of victims are discussed. Examples of the process of diagnosis and expert conclusions are given. This article is intended for physicians and forensic pathologists. The literature focusing on asphyxia by strangulation is reviewed. Data from Vilnius Hospitals and the State Forensic Medicine Service concerning strangulations performed between 2012 and 2014 are analyzed and include the findings of 5650 autopsies (36% asphyxia) and 4 survived victims. The predominant symptoms were neurological, cardiovascular, and respiratory symptoms. After asphyxia, patients should consult by a psychiatrist, ophthalmologist, gastroenterologist, and endocrinologist. A ligature mark was the most observable sign of asphyxia by neck strangulation. Only complications in the poststrangulation period were treated. Mechanical asphyxia must be identified as the main injury in the clinical diagnosis and encoded as ICD-10. PMID- 27364278 TI - Why We Need Postmortem Analysis of Cardiac Implantable Electronic Devices. AB - The prevalence of cardiac implantable electronic devices (CIEDs), pacemakers and implantable cardioverter defibrillators (ICDs) is increasing. However, postmortem analysis of CIEDs is not performed routinely. Fourteen consecutive CIEDs were analyzed. The indication for and date of implantation, technical data, CIED reprogramming, heart rhythm disturbances, patient demographics and medical consultations were investigated. Death during the first year after implantation was seen in 54%, whereof 71% consulted a physician within 10 days before death. The time of death was attributed to a particular day in 29%. There was a relationship between CIEDs and cause/manner of death in 50%. Although limited by a small sample size, this study advocates the routine postmortem CIED analysis for forensic and clinical purposes in selected cases. Patients with CIEDs seem to show an increased risk of death during the first year after implantation. The analysis of CIEDs can be helpful in evaluating the time/cause/manner of death. PMID- 27364279 TI - Characterization and Comparison of Injuries Caused by Accidental and Non accidental Blunt Force Trauma in Dogs and Cats. AB - Motor vehicle accidents (MVA) are often difficult to distinguish from non accidental injury (NAI). This retrospective case-control study compared animals with known MVA trauma against those with known NAI. Medical records of 426 dogs and cats treated after MVA and 50 after NAI were evaluated. Injuries significantly associated with MVA were pelvic fractures, pneumothorax, pulmonary contusion, abrasions, and degloving wounds. Injuries associated with NAI were fractures of the skull, teeth, vertebrae, and ribs, scleral hemorrhage, damage to claws, and evidence of older fractures. Odds ratios are reported for these injuries. MVA rib fractures were found to occur in clusters on one side of the body, with cranial ribs more likely to fracture, while NAI rib fractures were found to occur bilaterally with no cranial-caudal pattern. Establishing evidence based patterns of injury may help clinicians differentiate causes of trauma and may aid in the documentation and prosecution of animal abuse. PMID- 27364280 TI - Evaluation of Virulence Factors and Antifungal Susceptibility in Yeast Isolates from Postmortem Specimens. AB - Invasive fungal infections are a leading cause of morbidity and mortality in immunocompromised patients, especially in cases requiring a prolonged stay in the intensive care unit. A total of 99 yeast strains were isolated from 42 postmortem cases. In this study, virulence factors and antifungal susceptibility of these species were evaluated. The isolates were identified as Candida albicans (54), C. tropicalis (15), C. glabrata (12), C. parapsilosis (6), C. lipolytica (3), C. utilis (3), C. krusei (2), C. kefyr (1), and Cryptococcus neoformans (3). The most commonly isolated species was C. albicans, and no resistant species were determined. Despite the equal number of specimens, no secretion of significant virulence factors was associated with the postmortem specimen in the Candida species. Postmortem fungal investigations in forensic autopsies are useful in explaining cause of death in such cases, also may lead to protocols for the treatment of fungal infections and contribute to fungal pathogenesis and epidemiological data. PMID- 27364281 TI - Cutaneous (tPA) and Skeletal (TnI) mRNA as Markers of Aging in Contused Wound. AB - Wound age estimation is one of the most important forensic aspects. Troponin I (TnI) and many cytokines, for example, tissue plasminogen activator (tPA), are involved in wound inflammation and healing. Skeletal (TnI) and cutaneous (tPA) mRNA was detected using real-time PCR in 25 female albino rats. They were divided into 5 groups: control and 4 injured groups. Injured groups were sacrificed 1, 6, 24, and 30 h after inflicting contused wound. The expression levels of cutaneous (tPA) were decreased significantly at 1, 6, and 30 h after contusion (71.7%, 30.7 and 16.9%), while the expression levels of skeletal (TnI) were increased significantly at 1 and 6 h post-traumatic, then they gradually decreased until reaching normal levels at 24 h and assumed significantly lower levels at 30 h postcontusion. These results suggested that the determination of cutaneous (tPA) and skeletal (TnI) mRNA levels was useful for wound age estimation. PMID- 27364282 TI - Best Interest of the Child and Parental Alienation: A Survey of State Statutes. AB - State statutes regarding the best interests of the child (BIC) in deciding disputed custody were reviewed and independently coded with respect to three issues (i) the child's preference and any limits (ii) parental alienation and (iii) psychological maltreatment. Results revealed that many states allowed for the child's preferences to be considered and none qualified that preference when undue influence has occurred; parental alienation as a term was not found in any state statutes but 70% of the states included at least one BIC factor relevant to its core construct of the parent supporting the child's relationship to the other parent; and many states included a history of domestic violence or child abuse but only three states explicitly mentioned psychological maltreatment. These findings highlight yet another way in which the BICS factors lack specificity in ways that could negatively impact children caught in their parents' conflict. PMID- 27364283 TI - Popliteal Vein Blood Sampling and the Postmortem Redistribution of Diazepam, Methadone, and Morphine. AB - Postmortem redistribution (PMR) refers to the site- and time-related blood drug concentration variations after death. We compared central blood (cardiac and subclavian) with peripheral blood (femoral and popliteal) concentrations of diazepam, methadone, and morphine. To our knowledge, popliteal blood has never been compared with other sites. Intracardiac blood (ICB), subclavian blood (SB), femoral blood (FB), and popliteal blood (PB) were sampled in 30 cases. To assess PMR, mean concentrations and ratios were compared. Influence of postmortem interval on mean ratios was also assessed. Results show that popliteal mean concentrations were lower than those for other sites for all three drugs, even lower than femoral blood; mean ratios suggested that the popliteal site was less subject to PMR, and estimated postmortem interval did not influence ratios except for diazepam and methadone FB/PB. In conclusion, our study is the first to explore the popliteal site and suggests that popliteal blood is less prone to postmortem redistribution. PMID- 27364284 TI - Evaluation of Mastoid Process as Sex Indicator in Modern White Americans using Geometric Morphometrics. AB - Conventional methods for evaluating the mastoid as a sex indicator cannot determine whether mastoid shape is an independent and reliable sex indicator. Here, shape differences between the mastoids of 100 male and 100 female modern white Americans were statistically analyzed and visualized using the geometric morphometric method. Discriminant analysis was performed on mastoid size and shape. The relation between size and shape was analyzed to examine the effect of size on shape. In the results, mastoid size and shape were statistically significant sex indicators, while size factor explained 87.3% of the total variance of the shape variables. Nevertheless, females had relatively broader and shorter mastoid shape than males regardless of size, reflecting 12.7% of the total variance of the shape variables. In conclusion, mastoid size and shape were statistically significant sex indicators, while size may matter more in the mastoid than in other cranial parts in terms of sexual dimorphism. PMID- 27364285 TI - Effects of Parturition on Pelvic Age Indicators. AB - This research assessed whether parity has a differential effect on age indicators of the pelvis. The data were collected from the William M. Bass Donated Skeletal Collection. Age indicators of the pubic symphysis and auricular surface were assessed using the Todd, Suchey-Brooks, Lovejoy et al., and Buckberry and Chamberlain scoring systems. A transition analysis was conducted, and scoring systems of the pubic symphysis showed the parous female group transitioning between eight and 14 years earlier than the nulliparous female and male groups, and 1 and 7 years earlier using the auricular surface methods. A likelihood ratio test produced significantly different results between parous and nulliparous females using the pubic symphysis (p < 0.01) but not the auricular surface (p > 0.05). Although parous females were inaccurately assessed more often than nulliparous females, no correction of methods is necessary at this time as current standards take parity into account by utilizing a lumped female sample. PMID- 27364286 TI - Vertical Lip Position and Thickness in Facial Reconstruction: A Validation of Commonly Used Methods for Predicting the Position and Size of Lips. AB - This study examined several methods used to estimate oral fissure position, lip margin position, and lip thickness recommended by Angel, George, Lebedinskaya, Taylor, Wilkinson et al., Balueva and Veselovskaya. A sample of 86 lateral head cephalograms of adult subjects from central Europe were measured and the actual and predicted dimensions were compared. The best estimation for oral fissure position was "opposite the lower 3/4 mark of maxillary incisors" (error of 1.3 mm). Upper lip margin was predicted best by "upper 1/4 mark of maxillary incisors" (error of 1.7 mm), and lower lip margin by "cementum-enamel junction of mandibular incisors" (error of 2.3 mm). The regression equations of Wilkinson et al. displayed least error (1.3 mm and 1.8 mm, respectively) for upper and lower lip thickness, and method of George (error of 3.4 mm) for total lip thickness. PMID- 27364287 TI - Knowledge on DNA Success Rates to Optimize the DNA Analysis Process: From Crime Scene to Laboratory. AB - DNA analysis has become an essential intelligence tool in the criminal justice system for the identification of possible offenders. However, it appears that about half of the processed DNA samples contains too little DNA for analysis. This study looks at DNA success rates within 28 different categories of trace exhibits and relates the DNA concentration to the characteristics of the DNA profile. Data from 2260 analyzed crime samples show that cigarettes, bloodstains, and headwear have relatively high success rates. Cartridge cases, crowbars, and tie-wraps are on the other end of the spectrum. These objective data can assist forensics in their selection process.The DNA success probability shows a positive relation with the DNA concentration. This finding enables the laboratory to set an evidence-based threshold value in the DNA analysis process. For instance, 958 DNA extracts had a concentration value of 6 pg/MUL or less. Only 46 of the 958 low-level extracts provided meaningful DNA profiling data. PMID- 27364288 TI - Mitochondrial DNA Profiling of Illegal Tortoiseshell Products Derived from Hawksbill Sea Turtles. AB - The hawksbill sea turtle (Eretmochelys imbricata) is a highly endangered species, commonly poached for its ornate shell. "Tortoiseshell" products made from the shell are widely, although illegally, available in many countries. Hawksbills have a circumglobal distribution; thus, determining their origin is difficult, although genetic differences exist geographically. In the research presented, a procedure was developed to extract and amplify mitochondrial DNA from tortoiseshell items, in an effort to better understand where the species is being poached. Confiscated tortoiseshell items were obtained from the U.S. Fish and Wildlife Service, and DNA from 56 of them was analyzed. Multiple mitochondrial haplotypes were identified, including five not previously reported. Only one tortoiseshell item proved to be of Atlantic origin, while all others corresponded to genetic stocks in the Indo-Pacific region. The developed methodology allows for unique, and previously unattainable, genetic information on the illegal poaching of sea turtles for the decorative tortoiseshell trade. PMID- 27364289 TI - The Application of Voltammetric Analysis of Delta(9) -THC for the Reduction of False Positive Results in the Analysis of Suspected Marijuana Plant Matter. AB - The development of methodologies using inexpensive, fast, and reliable instrumention is desirable in illicit drug analysis. The purpose of this study was based on cyclic voltammetry technique to differentiate the electrochemical behavior of ?(9) -THC, the psychoactive substance in marijuana, and five different extract plants to yield false positive results after analysis protocol for cannabinoids using thin-layer chromatography and Fast Blue B salt. After applying a deposition potential of -0.5 V in a glassy carbon working electrode, the results indicated an anodic peak current at 0.0 V versus Ag/AgCl after addition of ?(9) -THC solution in the electrochemical cell, and limits of detection and quantification were 1.0 ng mL(-1) and 3.5 ng mL(-1) , respectively. Other interfering plants showed distinct amperometric responses. This methodology was useful to detect ?(9) -THC even in the presence of the Fast Blue B salt, which avoided false positive results for all the studied extract plants. PMID- 27364290 TI - Multivariate Classification of Original and Fake Perfumes by Ion Analysis and Ethanol Content. AB - The increased marketing of fake perfumes has encouraged us to investigate how to identify such products by their chemical characteristics and multivariate analysis. The aim of this study was to present an alternative approach to distinguish original from fake perfumes by means of the investigation of sodium, potassium, chloride ions, and ethanol contents by chemometric tools. For this, 50 perfumes were used (25 original and 25 counterfeit) for the analysis of ions (ion chromatography) and ethanol (gas chromatography). The results demonstrated that the fake perfume had low levels of ethanol and high levels of chloride compared to the original product. The data were treated by chemometric tools such as principal component analysis and linear discriminant analysis. This study proved that the analysis of ethanol is an effective method of distinguishing original from the fake products, and it may potentially be used to assist legal authorities in such cases. PMID- 27364291 TI - The Critical Angle for Perforation versus Ricochet of a .38 CAL. LRN Bullet on a Windshield. AB - From forensic point of view, it is important to clarify the condition whether ricochet or perforate for a bullet fired toward the automobile windshield. The purpose of this study was to specify the critical angle at which the ricochet of the fired bullet takes place. To estimate the result of firing, a rigid-body dynamics simulation of the bullet together with the test-firing using .38 CAL. LRN bullet was examined. It was found both from numerical simulation and firing test that when the incidence angle is <45 degrees , a complete perforation of the windshield was observed, whereas the bullet ricocheted remaining a characteristic damage on the windshield when the incidence angle is >60 degrees . To measure the static failure resistance of various windshields, static indentation test was also examined. PMID- 27364292 TI - The Effects of Burning and Mold Growth on the Chemical Composition of Firelog Fuels. AB - Firelogs consist of a cellulosic material, such as sawdust or wood particles, and a combustible binder (fuel). Historically, the fuel typically consisted of a petroleum-based (paraffin) wax; however, some manufacturers now include vegetable oils in their firelog fuels. To determine fuel composition, fuels from various brands of firelogs were extracted and analyzed by high-temperature gas chromatography-mass spectrometry (HTGC-MS) and a GC-MS with a polar column specific for the analysis of fatty acid methyl esters (FAMEs). Firelogs were also burned, allowed to grow mold, and analyzed by GC-MS to determine the effects that burning and mold growth have on firelog fuel composition. Mold did not tend to preferentially degrade any of the fatty acids. Burning caused a decrease in the relative amount of all of the fatty acids present in the vegetable oil fuel, with a greater effect on unsaturated fatty acids than saturated ones. PMID- 27364293 TI - Contactless Visualization of Latent Fingerprints on Nonporous Curved Surfaces of Circular Cross Section. AB - Nondestructive techniques for gathering evidence are important in the field of forensics. Due to the geometry of the substrates, nondestructive visualization of fingermarks on curved surfaces remains challenging. A novel contactless technique was developed for visualizing and recording fingermark patterns on nonporous curved surfaces of circular cross section. The technique utilizes a plane mirror to transmit rays from a light source to illuminate the area of interest for fingermark visualization. The fingermark acquisition system consists of a digital single-lens reflex (SLR) camera, a plane mirror, and a white light source. Mathematical equations are used to calculate the mirror size. Experiments were performed on various curved surfaces to determine the feasibility and effectiveness of the technique. Spectral Image Validation and Verification (SIVV) was used to analyze the captured images. The results of this study indicate that the technique described here is able to reveal fingermark patterns on curved surfaces of circular cross section. PMID- 27364294 TI - Enhancement of Latent Fingerprints on Fabric Using the Cyanoacrylate Fuming Method Followed by Infrared Spectral Mapping. AB - A method has been developed for the visualization of latent fingerprints on fabrics, which is based upon cyanoacrylate (superglue) fuming followed by imaging using an infrared microscope. Results show that imaging on smooth, shiny fabrics such as polyester, silk, nylon, and acetate of different colors and patterns can give an improvement over existing enhancement methods. Results for cotton and polycotton were less successful and it is thought this may be due a combination of the presence of the carbonyl functional group in these fabrics as well as their absorbency to fingerprint sweat. The carbonyl peak (1700 cm(-1) ) provided the optimum spectroscopic feature to map and image a fingerprint. Comparisons between infrared mapping at a specific frequency range and principal component analysis showed that improved imaging was obtained with principal component analysis. PMID- 27364295 TI - How Much Can a Forensic Laboratory Do to Discriminate Questioned Ink Entries? AB - Questioned document examiners are frequently required to determine whether the questioned ink entries on a document are written with the same ink, either for forged document identification or relative ink dating. How many methods are sufficient to discriminate potentially different inks? In this paper, 18 blue ballpoint inks were first nondestructively examined with a video spectral comparator. The ink entries were subsequently extracted with organic solvents for analysis of the volatile solvents and dyes by GC/MS, TLC, and LC-MS/MS. The 18 ink samples were divided into 10, 9, 12, and 14 categories by these four methods, respectively. With the combined results, there were only two inks that remained indistinguishable, but they were further differentiated by microscopy. Therefore, to achieve effective discrimination of ballpoint ink entries, the authors suggest that a complete examination should include an analysis of their optical features, volatile solvents, and dyes as well as the ink quality. PMID- 27364296 TI - Forensic Investigation of Formaldehyde in Illicit Products for Hair Treatment by DAD-HPLC: A Case Study. AB - The illegal use of formalin (commercial formaldehyde) in cosmetic products harms the health of individuals exposed to this substance. Over the last years, the commercial availability of these products, especially those containing irregular dosage of formaldehyde, has increased in Brazil. This work analyzes some products for hair treatment available in the Brazilian market and verifies their safety. The adopted analytical methodology involved sample derivatization with 2,4 dinitrophenylhydrazine, followed by high-performance liquid chromatography with ultraviolet detection (UV-VIS) at lambda = 365 nm. The limit of quantification is 2.5 * 10-3% w/w, and the recovery tests were around 93%. Some of the samples contained high and illegal formaldehyde levels ranging from 9% to 19% (w/w) and others presented suitable concentrations of the analyte. On the basis of the results, this work discusses the efficiency and practicality of this analytical method for forensic purposes. PMID- 27364297 TI - Counterfeit Adderall Containing Aceclofenac from Internet Pharmacies. AB - A nontargeted approach based on liquid chromatography equipped with a quadrupole time-of-flight mass detector (LC-MS Q-TOF) joined to nuclear magnetic resonance (NMR) analysis allowed rapid identification and quantification of the anti inflammatory drug aceclofenac in illegal Adderall tablets. The largest chromatographic peak had m/z = 354.030 and m/z = 376.012 matching, respectively, the ionic structures (M + H)+ and (M + Na)+ of a molecule M. The accurate mass data generated the molecular formula C16 H13 Cl2 NO4 . A screening of the pharmaceutical active substances having that molecular formula together with the MS/MS fragmentation pattern suggested aceclofenac. Aceclofenac structure was unambiguously confirmed by 1 H and 13 C NMR experiments. The aceclofenac content was 90 mg/tablet (RSD 2%) as detected by quantitative NMR. Information on the identity and content of illegal drugs is required for legal purposes; it supports in evaluating the effective impact on users safety, and it is useful for control laboratories using a targeted approach in their analytical activities. PMID- 27364298 TI - Determination of Both Fetus' and Mother's Blood Type from an Autopsy Case Immersed in Formalin for Over 50 Years. AB - A female fetus which had been immersed in formalin for more than 50 years was found in Japan. Because no liquid blood could be obtained, we tried to use immunohistochemistry (IHC) methods to tissue samples obtained at autopsy to identify both the fetal and mother's blood type. We detected B antigens on endothelial cells in paraffin sections of the fetal organs. Furthermore, we observed both anti-A- and anti-B-positive red blood cells in the intervillous space, which is indicative of the mother's blood type. To our knowledge, this is the first case report on determining the blood type of both the fetus and the mother from tissue immersed in formalin for such a long time. The results suggest that IHC is valuable for the determination of ABO blood type in circumstances of long postmortem duration and unfavorable storage conditions. PMID- 27364299 TI - Left Diaphragm Laceration Due to Cardiopulmonary Resuscitation. AB - External cardiac massage is the essential life-saving gesture for the management of any cardiac arrest. Since the 1960s, many recommendations have been published to improve the effectiveness of chest compressions alongside the development of automated systems intended to maximize the chances of survival. The use of these manual and/or instrumental techniques can cause secondary injuries, of which rib fractures are the most commonly observed by forensic pathologists. However, a comprehensive review of the literature seldom highlights reports of injuries to the abdomen, even less so to the diaphragm. In this observation, an iatrogenic left diaphragmatic laceration for the first time is described, as a result of manual and instrumental cardiopulmonary resuscitation, in a victim from an intrathoracic wound caused by a bladed weapon. PMID- 27364300 TI - A Case of Lethal Idiopathic Plasmacytic Lymphadenopathy with Polyclonal Hypergammaglobulinemia: A Medical Challenge for the Forensic Pathologist. AB - A rare case of lethal idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hyperimmunoglobulinemia with chronic renal failure is described. A 40 year-old woman who had suffered from upper airways disease was admitted to the Emergency Room with acute renal failure and hypergammaglobulinemia. She developed pericardial effusion, a pruritic rash, splenomegaly and fell into a coma after 6 days. Multiple myeloma, infection, collagenopathy, and coagulopathy were ruled out. Finally, a form of malignant hypergammapathy was suspected. At autopsy, lymph nodes were infiltrated by polyclonal plasma cells and lymphocytes, with erythrophagocytosis features; immunohistochemistry confirmed the plasma cells (CD138+), with a prevalence of kappa-positive cells, B (CD20+) and T (CD3+) cells. Kidneys showed advanced glomerulosclerosis containing similar infiltrates. The cause of death was IPL with polyclonal hypergammaglobulinemia and advanced renal failure. Similar cases are unusual, and possible medical liability associated with failure to diagnose and treat idiopathic plasmacytic lymphadenopathy deserves discussion and further studies. PMID- 27364301 TI - Fatal Phenol Toxicity Following Attempted Tattoo Removal. AB - Tattoo removal is increasingly required as the number of, particularly young, people acquiring tattoos is increasing. A 21-year-old man is reported who underwent attempted removal of large dragon tattoo utilizing a tattoo machine that injected a phenol-containing solution. At the end of the 3-h procedure, he collapsed and died. At autopsy, large areas of white skin discoloration with focal necrosis and sloughing were present overlying areas of previous tattooing. Histological examination showed collections of eosinophilic fluid with a minimal chronic inflammatory infiltrate in better preserved areas, with focal areas of dermal necrosis. Toxicology was positive for phenol in cardiac blood and liver tissue. There were no underlying organic disease or injuries present which could have caused or contributed to death. This idiosyncratic method of tattoo removal involving subcutaneous injection of phenol had resulted in death most likely from cardiotoxicity. PMID- 27364302 TI - The Decipherment of Latent White Board Entries. AB - This case involves an incriminating message written on a white board and erased before the investigators seized the evidence. Investigators inquired about the possibility of recovering the entries and subsequently submitted the board to the Documents and Digital Evidence Branch for examination. In an attempt to recover latent handwritten entries, examinations were conducted utilizing the Foster and Freeman Video Spectral Comparator 6000/Hyper Spectral (VSC 6000/HS). Latent handwritten entries were observed with the use of an excitation band-pass filter in the range of 485 nm-610 nm with a longpass barrier filter at 645 nm in front of the camera lens of the VSC 6000/HS. Entries were also recovered and imaged using an alternate light source with the Phase One (P65) imaging system. Multiple latent handwritten entries were recovered utilizing various instruments and lighting techniques. This report discusses the details concerning the examination and the results. PMID- 27364303 TI - Survival of Very High Blood Alcohol Concentration Without Consequential Damage in a Patient Without a Previous Substance Use Disorder. AB - Intoxications with alcohol may lead to death depending on (maximum) blood alcohol concentration (BAC) and accompanying factors such as liver function, tolerance, and comedication. Death may occur due to ethanol-induced respiratory depression and/or aspiration of gastric content (due to an impaired gag reflex); thus, securing of the airway and ventilation is occasionally necessary. A case of a 58 year-old female patient with depression who demonstrated a very high BAC of 8.68 gm/L (0.868%) following ingestion of large amounts of alcohol with suicidal intent is presented. Intubation and ventilation were life-saving, and the patient did not develop any physical or consequential damage. As the patient had not regularly used alcohol or any other psychotropic agent, tolerance could be ruled out. This case emphasizes the necessity of rapid securing of the airway in patients with alcohol intoxication and respiratory depression and, furthermore, illustrates the large interindividual differences regarding ethanol susceptibility. PMID- 27364305 TI - Outcomes of infants with abdominal wall defects over 18years. AB - BACKGROUND/PURPOSE: Infants with abdominal wall defects (AWD) are at risk of poor outcomes including prolonged hospitalization, infections and mortality. Our objective was to describe and compare the outcomes of infants admitted with gastroschisis and omphalocele over 18years. METHODS: Population-based study of clinical data and outcomes of live-born infants with AWD admitted to all tertiary level neonatal intensive care units in New South Wales and Australian Capital Territory from 1992 to 2009. RESULT: There were 502 infants with AWD - 336 gastroschisis, 166 omphalocele. Infants with gastroschisis required a longer duration of total parenteral nutrition (19 vs 4days, p<0.05), longer hospitalization (28 vs 15days, p<0.05) and had a higher rate of systemic infection [23.5% vs 13.3%, OR 1.77 (1.15-2.74), p<0.05] compared to infants with omphalocele. Overall, omphalocele infants had higher mortality rate compared to gastroschisis infants [OR 2.77 (1.53, 5.04), p<0.05]. Gastroschisis mortality rates increased from epoch 1 to epoch 3 (4.2% to 8.8%). CONCLUSION: Compared to infants with omphalocele, infants with gastroschisis required significantly longer hospitalization and parenteral nutrition with higher rates of infection. Infants with omphalocele had higher overall mortality rates. However, there has been an increase in the gastroschisis mortality rates but the cause for this is unclear. PMID- 27364306 TI - Submucosal nerve diameter of greater than 40 MUm is not a valid diagnostic index of transition zone pull-through. AB - BACKGROUND: Submucosal nerve hypertrophy is a feature of the transition zone in Hirschsprung disease and has been used as a primary diagnostic feature of transition zone pull-through for patients with persistent obstructive symptoms after their initial surgery. Most published criteria for identification of hypertrophy rely on a nerve diameter of greater than 40MUm, based primarily on data from a relatively small number of infants with Hirschsprung disease and controls. The validity of these objective measures has not been validated in appropriate controls for post-pull-through patients. SCIENTIFIC APPROACH: The primary pull-through specimens and post pull-through biopsies +/- redo pull through resections from a series of 9 patients with Hirschsprung disease were reviewed to assess the prevalence of submucosal nerves >40MUm in diameter and 400* microscopic fields containing two or more such nerves. Similar data from multiple colonic locations were collected from a series of 40 non-Hirschsprung autopsy and surgical controls. RESULTS: The overwhelming majority of Hirschsprung patients harbored submucosal nerves >40MUm in their post-pull-through specimens independent of other features of transition zone pathology, and despite normal innervation at the proximal margins of their initial resections. Measurement of submucosal nerve diameters in autopsy and surgical non-Hirschsprung control samples indicated that nerves >40MUm are normal in the distal rectum after 1year of age and are found in more proximal colon at older ages. CONCLUSIONS: These results suggest that diagnostic criteria currently used to recognize submucosal nerve hypertrophy in the neorectum after a pull-through for Hirschsprung disease are not justified and should not be regarded as definitive evidence for transition zone pull-through. PMID- 27364307 TI - Effects of Quilting Suture Interval on Donor Site Seromas After Breast Reconstruction With Latissimus Dorsi Muscle Flap: A Randomized Trial. AB - BACKGROUND: Although breast reconstruction using a deep inferior artery perforator flap has been increasing, using a latissimus dorsi (LD) muscle flap is still the favored method for Asian female patients with breast cancer. However, because the incidence of donor site seromas has been relatively high, a quilting method on the donor cavity or insertion of drainage tube has been used to reduce the incidence and/or severity of postoperative seroma. We evaluated the effects of different intervals of quilting sutures on the postoperative drainage volume and components of seroma fluid. PATIENTS AND METHODS: A total of 36 patients with breast cancer underwent partial or total mastectomy with LD flap reconstruction. They were randomized into 3 groups according to the interval of quilting sutures: nonquilting (n = 10), 6-cm quilting (n = 14), and 3-cm quilting (n = 12). The clinicopathologic factors and time to drain removal, drainage volume, frequency of aspiration, and serous fluid components were investigated. RESULTS: No statistically significant differences were found in the clinicopathologic factors among the 3 groups. The time to drain removal was significantly shorter in the 6 cm quilting and 3-cm quilting groups than in the nonquilting group (P = .039 and P = .041, respectively). The total volume of drainage from the donor site was also decreased in the quilting groups (6-cm group, P = .046; 3-cm group, P = .021). The seroma components were not different among the 3 groups. CONCLUSION: Performing quilting sutures on LD flap donor sites is an effective method to reduce the volume of postoperative seroma. The present findings showed that a 6 cm suture interval is appropriate. PMID- 27364309 TI - Photonic Crystals: Tunable Design of Structural Colors Produced by Pseudo-1D Photonic Crystals of Graphene Oxide (Small 25/2016). AB - The production of structural colors based on graphene oxide (GO) pseudo-one dimensional photonic crystals (p1D-PhCs) in the visible spectrum is reported on page 3433 by W. Qi and co-workers. The structural colors could be tuned by simply changing either the volume or concentration of the aqueous GO dispersion. Moreover, GO p1D-PhCs exhibit visible and rapid responsiveness to humidity. PMID- 27364312 TI - Reformed smokers have survival benefits after head and neck cancer. AB - Smoking tobacco is the main risk factor for head and neck cancer, is proportional to the number of pack years (number of packs smoked/day x number of years of smoking), and is reduced when the patient stops smoking. Current molecular evidence has suggested that tobacco-related cancers could be clinically more aggressive than cancers in non-smokers, particularly in the head and neck. However, clinical studies have not uniformly reproduced the relation between survival and tobacco, possibly because they ignore the health benefit that reformed smokers obtain during the period between giving up smoking and the diagnosis of cancer, which is not shared by those who continue to smoke and develop cancer. We have investigated the survival of reformed smokers, non smokers, and continuing smokers after a diagnosis of head and neck cancer. The data of patients with head and neck cancer from 1992 -2013 from the Cancer Genome Atlas database were analysed using a multivariate Cox's regression model for survival, and Kaplan-Meier curves were produced for smoking history. A total of 521 patients were treated for head and neck cancer, and there was a significant difference in survival between reformed and non-smokers on the one hand, and current smokers on the other (p=0.02). The significance increased when reformed smokers were grouped according to their duration of abstinence and time of diagnosis of cancer (>15 and <=15 years, p<0.01). Smoking history was a significant prognostic factor in the multivariate Cox's regression model when analysed with age, stage, grade, and site. We conclude that reformed smokers have a survival benefit in head and neck cancer. PMID- 27364313 TI - Effects of 25-hydroxycholecalciferol supplementation in maternal diets on milk quality and serum bone status markers of sows and bone quality of piglets. AB - Twenty primiparous sows were allocated to two treatments to evaluate the effects of maternal 25-hydroxycholecalciferol (25OHD3 ) supplementation during gestation and lactation on milk quality and serum bone status markers of sows and bone quality of piglets. Immediately after mating, sows were randomly allotted to one of two diets supplemented with 50 ug/kg 25OHD3 or basal diets without 25OHD3 . Blood and milk samples were obtained. At birth and weaning, 10 piglets from each treatment were killed for bone quality analysis. 25OHD3 -fed sows provided one more piglet at farrowing and 1.17 more piglets at weaning than sows fed basal diets. The contents of solids not-fat, protein, fat or lactose were increased in milk from days 7 and 14 of lactation in 25OHD3 -supplemented sows and 25OHD3 concentrations in milk were increased by dietary 25OHD3 supplementation. Dietary 25OHD3 supplementation increased serum alkaline phosphatase activity but had no effect on serum tartrate-resistant acid phosphatase activity of sows. Maternal 25OHD3 supplementation improved bone strength, density and ash content of newborn piglets rather than those of weaning piglets. In conclusion, 25OHD3 supplementation in maternal diets improved reproductive performance, milk quality and bone status of sows as well as bone quality of newborn piglets. PMID- 27364314 TI - The contribution of apoptosis and necrosis in freezing injury of sea urchin embryonic cells. AB - Sea urchins have recently been reported to be a promising tool for investigations of oxidative stress, UV light perturbations and senescence. However, few available data describe the pathway of cell death that occurs in sea urchin embryonic cells after cryopreservation. Our study is focused on the morphological and functional alterations that occur in cells of these animals during the induction of different cell death pathways in response to cold injury. To estimate the effect of cryopreservation on sea urchin cell cultures and identify the involved cell death pathways, we analyzed cell viability (via trypan blue exclusion test, MTT assay and DAPI staining), caspase activity (via flow cytometry and spectrophotometry), the level of apoptosis (via annexin V-FITC staining), and cell ultrastructure alterations (via transmission electron microscopy). Using general caspase detection, we found that the level of caspase activity was low in unfrozen control cells, whereas the number of apoptotic cells with activated caspases rose after freezing-thawing depending on cryoprotectants used, also as the number of dead cells and cells in a late apoptosis. The data using annexin V-binding assay revealed a very high apoptosis level in all tested samples, even in unfrozen cells (about 66%). Thus, annexin V assay appears to be unsuitable for sea urchin embryonic cells. Typical necrotic cells with damaged mitochondria were not detected after freezing in sea urchin cell cultures. Our results assume that physical cell disruption but not freezing-induced apoptosis or necrosis is the predominant reason of cell death in sea urchin cultures after freezing-thawing with any cryoprotectant combination. PMID- 27364316 TI - Evaluation of predictive capacities of biomarkers based on research synthesis. AB - The objective of diagnostic studies or prognostic studies is to evaluate and compare predictive capacities of biomarkers. Suppose we are interested in evaluation and comparison of predictive capacities of continuous biomarkers for a binary outcome based on research synthesis. In analysis of each study, subjects are often classified into two groups of the high-expression and low-expression groups according to a cut-off value, and statistical analysis is based on a 2 * 2 table defined by the response and the high expression or low expression of the biomarker. Because the cut-off is study specific, it is difficult to interpret a combined summary measure such as an odds ratio based on the standard meta analysis techniques. The summary receiver operating characteristic curve is a useful method for meta-analysis of diagnostic studies in the presence of heterogeneity of cut-off values to examine discriminative capacities of biomarkers. We develop a method to estimate positive or negative predictive curves, which are alternative to the receiver operating characteristic curve based on information reported in published papers of each study. These predictive curves provide a useful graphical presentation of pairs of positive and negative predictive values and allow us to compare predictive capacities of biomarkers of different scales in the presence of heterogeneity in cut-off values among studies. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27364317 TI - Chronic obstructive pulmonary disease prognostic score: A new index. AB - BACKGROUND: The evaluation of chronic obstructive pulmonary disease (COPD) has been shifting from spirometry to focus on the patients' overall health. Despite the existence of many COPD prognostic scales, there remains a large gap for improvement, in particular a scale that incorporates the current focus on overall health. METHODS: We proposed a new prognostic scale (the COPD Prognostic Score) through discussion among the authors based on published studies. Validation was retrospective, using data from the National Emphysema Treatment Trial. RESULTS: The scores ranged from 0-16, where 16 indicated the poorest prognosis. We assigned 4 points each for forced expiratory volume in one second (%predicted), the modified Medical Research Council dyspnea scale, and age; 2 points for the hemoglobin level; and one point each for decreased activity and respiratory emergency admission in the last two years. The validation cohort included 607 patients and consisted of 388 men (73.9%) and 219 women (36.1%), mean age 67 +/- 6 years and an average forced expiratory volume in one second (% predicted) of 27 +/- 7%. A one-point increase in the score was associated with increased all-cause death, with a hazard ratio of 1.28 (95%CI: 1.21-1.36. P < 0.001). The areas under the receiver operating characteristic curves for two-year and five-year all-cause death for the new scale were 0.72 and 0.66, respectively. These values were higher than those given by the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index and age, dyspnea, airway obstruction (ADO) index. CONCLUSION: The preliminary validation for a new COPD prognostic scale: the COPD Prognostic Score was developed with promising results thus far. Above mentioned 16-point score accurately predicted 2-year and 5-year all-cause mortality among subjects who suffered from severe and very severe COPD. PMID- 27364315 TI - The International Epidemiology of Lung Cancer: Latest Trends, Disparities, and Tumor Characteristics. AB - INTRODUCTION: Our aim was to update global lung cancer epidemiology and describe changing trends and disparities. METHODS: We presented country-specific incidence and mortality from GLOBOCAN 2012 by region and socioeconomic factors via the Human Development Index (HDI). Between- and within-country incidence by histological type was analyzed by using International Agency for Research on Cancer data on cancer incidence on five continents. Trend analyses including data from the International Agency for Research on Cancer, cancer registries, and the WHO mortality database were conducted using joinpoint regression. Survival was compared between and within countries and by histological type. RESULTS: In 2012, there were 1.82 and 1.59 million new lung cancer cases and deaths worldwide, respectively. Incidence was highest in countries with a very high HDI and lowest in countries with a low HDI (42.2 versus 7.9 in 100,000 for males and 21.8 versus 3.1 in 100,000 for females, respectively). In most countries with a very high HDI, as incidence in males decreased gradually (ranging from -0.3% in Spain to 2.5% in the United States each year), incidence in females continued to increase (with the increase ranging from 1.4% each year in Australia to 6.1% in recent years in Spain). Although histological type varied between countries, adenocarcinoma was more common than squamous cell carcinoma, particularly among females (e.g., in Chinese females, the adenocarcinoma-to-squamous cell carcinoma ratio was 6.6). Five-year relative survival varied from 2% (Libya) to 30% (Japan), with substantial within-country differences. CONCLUSIONS: Lung cancer will continue to be a major health problem well through the first half of this century. Preventive strategies, particularly tobacco control, tailored to populations at highest risk are key to reducing the global burden of lung cancer. PMID- 27364319 TI - Effect of intraoperative navigation on operative time in 1-level lumbar fusion surgery. AB - The use of intraoperative image guided navigation (NAV) in spine surgery is increasing. NAV is purported to improve the accuracy of pedicle screw placement but has been criticized for potentially increasing surgical cost, a component of which may be prolongation of total operative time due to time required for setup and intra-operative imaging and registration. In this study, we examine the effect of the introduction of O-Arm conical CT spinal navigation on surgical duration. We retrospectively analyzed consecutive freehand (FH) (n=63) and NAV (n=70) 1-level lumbar transpedicular instrumentation cases at a single institution by a single surgeon. We recorded setup and procedure time for each case. NAV was associated with significantly shorter total operative time for 1 level lumbar fusions compared to FH (4:30+/-0:42 hours vs. 4:53+/-0:39hours, p=0.0013). This shortening of total operative time was realized despite a trend toward slightly longer setup times with NAV. We also found a significant decrease in operative length over time in NAV but not FH cases, indicative of a "learning curve" associated with NAV. The use of NAV in 1-level lumbar transpedicular instrumentation surgery is associated with significantly shorter total operative time compared to the FH technique, and its efficiency improves over time. These data should factor into cost-effectiveness analyses of the use of NAV for these cases. PMID- 27364320 TI - Spinal epidural abscess with a rapid course in young healthy infantry recruits with multiple skin lacerations. AB - In recent years, there has been high prevalence of Staphylococcus aureus (S. aureus) infection among soldiers in the Israeli military, with devastating sequelae in several cases. Emergency department physicians have developed a high level of suspicion for spinal epidural abscess (SEA) in patients presenting known risk factors; however, SEA is a particularly elusive diagnosis in young healthy adults with no history of drug abuse. We review three cases of SEA secondary to methicillin-sensitive S. aureus (MSSA) infection in young healthy soldiers without known risk factors. We retrospectively reviewed clinical files of soldiers treated at our Medical Center from 2004-2015 to identify patients diagnosed with SEA. Those aged less than 30years with no history of intravenous drug use, spine surgery or spine trauma were included in the study. Three young army recruits met the inclusion criteria. These young men developed SEA through extension of MSSA infection to proximal skin and soft tissue from impetigo secondary to skin scratches sustained during "basic" training. All presented with mild nuchal rigidity and severe persistent unremitting lancinating radicular pain. Although healthy at baseline, they had a severe, rapidly progressive course. Following urgent surgery, two patients recovered after rehabilitation; one remained with paraparesis at late follow-up. Neurological deficits and systemic evidence of S. aureus infection progressed rapidly in these young healthy SEA patients with no history of drug abuse, emphasizing the critical role of timely MRI, diagnosis, and surgery. PMID- 27364318 TI - Oxidative DNA damage stalls the human mitochondrial replisome. AB - Oxidative stress is capable of causing damage to various cellular constituents, including DNA. There is however limited knowledge on how oxidative stress influences mitochondrial DNA and its replication. Here, we have used purified mtDNA replication proteins, i.e. DNA polymerase gamma holoenzyme, the mitochondrial single-stranded DNA binding protein mtSSB, the replicative helicase Twinkle and the proposed mitochondrial translesion synthesis polymerase PrimPol to study lesion bypass synthesis on oxidative damage-containing DNA templates. Our studies were carried out at dNTP levels representative of those prevailing either in cycling or in non-dividing cells. At dNTP concentrations that mimic those in cycling cells, the replication machinery showed substantial stalling at sites of damage, and these problems were further exacerbated at the lower dNTP concentrations present in resting cells. PrimPol, the translesion synthesis polymerase identified inside mammalian mitochondria, did not promote mtDNA replication fork bypass of the damage. This argues against a conventional role for PrimPol as a mitochondrial translesion synthesis DNA polymerase for oxidative DNA damage; however, we show that Twinkle, the mtDNA replicative helicase, is able to stimulate PrimPol DNA synthesis in vitro, suggestive of an as yet unidentified role of PrimPol in mtDNA metabolism. PMID- 27364321 TI - Lactate recovery kinetics in response to high-intensity exercises. AB - PURPOSE: The aim of this study was to investigate lactate recovery kinetics after high-intensity exercises. METHODS: Six competitive middle-distance runners performed 500-, 1000-, and 1500-m trials at 90 % of their current maximal speed over 1500 m. Each event was followed by a passive recovery to obtain blood lactate recovery curves (BLRC). BLRC were fitted by the bi-exponential time function: La(t) = La(0) + A 1(1-e (-gamma1t) ) + A 2(1-e (-gamma2t) ), where La(0) is the blood lactate concentration at exercise completion, and gamma 1 and gamma 2 enlighten the lactate exchange ability between the previously active muscles and the blood and the overall lactate removal ability, respectively. Applications of the model provided parameters related to lactate release, removal and accumulation rates at exercise completion, and net amount of lactate released during recovery. RESULTS: The increase of running distance was accompanied by (1) a continuous decrease in gamma 1 (p < 0.05), (2) a primary decrease (p < 0.05) and then a stabilization of gamma 2, and (3) a constant increase in blood concentrations (p < 0.05) and whole body accumulation of lactate (p < 0.05). Estimated net lactate release, removal and accumulation rates at exercise completion, as well as the net amount of lactate released during recovery were not significantly altered by distance. CONCLUSION: Alterations of lactate exchange and removal abilities have presumably been compensated by an increase in muscle-to-blood lactate gradient and blood lactate concentrations, respectively, so that estimated lactate release, removal and accumulation rates remained almost stable as distance increased. PMID- 27364323 TI - Neurofilament in CSF-A biomarker of disease activity and long-term prognosis in multiple sclerosis. PMID- 27364322 TI - Measuring treatment satisfaction in MS: Is the Treatment Satisfaction Questionnaire for Medication fit for purpose? AB - BACKGROUND: The Treatment Satisfaction Questionnaire for Medication (TSQM) was designed to assess patient treatment satisfaction in chronic diseases. Its performance has not been examined in multiple sclerosis (MS). The 14 items of the TSQM cover four domains: Effectiveness, Side Effects, Convenience, and Global Satisfaction. OBJECTIVE: To evaluate performance of the TSQM in patients with relapsing MS, using data collected from the TENERE study (NCT00883337), in which 324 patients received oral teriflunomide or subcutaneous interferon beta-1a for ?48 weeks. METHODS: Five measurement properties were examined using traditional psychometric methods: data completeness, scale-to-sample targeting, scaling assumptions, reliability (including test-retest), and construct validity (internal: item-level scaling success, confirmatory factor analysis, and exploratory factor analysis; external: convergence, discrimination, and group differences). RESULTS: There were few (<2%) missing item data; domain scores could be computed for all patients. Score distributions were skewed toward higher satisfaction; two domains had marked ceiling effects. Scaling assumptions were supported. Internal consistency reliability was high (Cronbach's alpha > 0.90). Internal validity tests supported item groupings. Correlations supported convergent and discriminant construct validity; hypothesis testing supported group differences validity. CONCLUSION: This investigation found the TSQM to be a useful tool, exhibiting good psychometric measurement properties in patients with relapsing MS in the TENERE study. PMID- 27364324 TI - The use of laboratory gait analysis for understanding gait deterioration in people with multiple sclerosis. AB - Laboratory gait analysis or three-dimensional gait analysis (3DGA), which uses motion capture, force plates and electromyography (EMG), has allowed a better understanding of the underlying mechanisms of gait deterioration in patients with multiple sclerosis (PwMS). This review will summarize the current knowledge on multiple sclerosis (MS)-related changes in kinematics (angles), kinetics (forces) and electromyographic (muscle activation) patterns and how these measures can be used as markers of disease progression. We will also discuss the potential causes of slower walking in PwMS and the implications for 3DGA. Finally, we will describe new technologies and methods that will increase precision and clinical utilization of 3DGA in PwMS. Overall, 3DGA studies have shown that functionality of the ankle joint is the most affected during walking and that compensatory actions to maintain a functional speed may be insufficient in PwMS. However, altered gait patterns may be a strategy to increase stability as balance is also affected in PwMS. PMID- 27364325 TI - Neurostatus e-Scoring improves consistency of Expanded Disability Status Scale assessments: A proof of concept study. AB - BACKGROUND: To improve the consistency of standardized Expanded Disability Status Scale (EDSS) assessments, an electronic data capture tool and analysis tool was developed, Neurostatus e-Scoring (NESC). This tool allows real-time feedback by comparing entries with established scoring rules. OBJECTIVE: To test whether using NESC reduces inconsistencies as compared to the paper-and-pencil version of the Expanded Disability Status Scale (pEDSS). METHODS: In all, 100 multiple sclerosis (MS) patients were assessed in random order on the same day by pairs of neurologists, one using pEDSS and one NESC. We compared inter-rater reliability and frequency of inconsistencies in Neurostatus subscores, functional system (FS) scores, ambulation and EDSS steps. RESULTS: Inconsistencies of any type were more likely to occur when using pEDSS (mean odds ratio (95% confidence interval (CI)) = 2.93 (1.62; 5.29)). This was also the case for FS score inconsistencies (2.54 (1.40; 4.61)) and more likely for patients in the lower EDSS range (?3.5 vs >3.5) (5.32 (1.19; 23.77)). Overall, inter-rater agreement for the assessed Neurostatus subscores was high (median and inter-quartile range = 0.84 (0.73, 0.81)). CONCLUSION: Our data provide class II evidence that the use of NESC increases consistency of standardized EDSS assessments, and may thus have the potential to decrease noise and increase power of MS clinical trials. PMID- 27364326 TI - Trajectory of MS disease course for men and women over three eras. AB - BACKGROUND: Heterogeneity in disease course exists within multiple sclerosis (MS) subtypes. OBJECTIVE: The objective was to estimate disease course heterogeneity over three distinct onset periods (pre-1995, 1995-2004, and 2005-present) for men and women. METHODS: Group-based trajectory model (GBTM) was used to estimate clusters of patients following stable or unstable disease progression trajectories based on the Expanded Disability Status Scale (EDSS). Inception cohorts were generated from the Montreal Neurological Institute MS Clinic registry. Stable trajectories were defined as an EDSS ?3.0 and change ?1 point over the study period. Annualized relapse rate (ARR) based on the first 5 years of disease was an explanatory variable. RESULTS: Proportion of women classified as stable was 0% for pre-1995, 69.0% for 1995-2004, and 83.9% post-2005; for men, these proportions were 18.4%, 41.4%, and 53.8%, respectively. Men had lower percentage of stable disease than women in both post-1995 cohorts (chi-square p < 0.0001). ARR was associated with higher disability trajectories in both post-1995 cohort (odds ratios >1.0) but not in the pre-1995 cohort. CONCLUSION: Large proportions of patients remain stable at their initial disability level for at least 15 years. Higher ARR increases the odds of patients being in a higher disability trajectory in the latter cohorts. PMID- 27364327 TI - Low-Activity Kidney Transplant Center, A Single-Center Experience: Early Care as a Major Challenge. AB - OBJECTIVES: In many countries, some kidney transplants are performed in small centers, from which clinical data are rarely specifically reported. The aim of this study was to describe patient and graft survival rates and their correlates in a low-activity kidney transplant center. MATERIALS AND METHODS: We performed a retrospective cohort study of all patients who underwent transplant between January 2002 and May 2012 at a university hospital. Patient, graft, and death censored graft survival rates were assessed with Kaplan-Meier analyses and compared by log-rank test, with associated factors analyzed by Cox proportional hazards modeling. RESULTS: Among a total of 162 patients, the mean age was 41.8 +/- 13.5 years, and 92% received a living-donor graft. At 1, 3, and 5 years, patient survival was 88.6%, 86%, and 82.9%. Graft survival was 86.9%, 83%, and 77%, and death-censored graft survival was 98.1%, 96.6%, and 92.9% at the same time points. Most graft losses were due to patient death from infection and occurred within the first year after transplant. After adjustment, age over 42 years (hazard ratio of 3.94; 95% confidence interval, 1.39-11.13), deceased donor graft (hazard ratio of 11.41; 95% confidence interval, 1.2-108.35), and higher average education (hazard ratio of 4.96; 95% confidence interval, 1.01-24.32) were independently associated with graft loss. CONCLUSIONS: The observed patient and graft survival rates were similar to those described in large databases; however, early mortality remains a major challenge. Improving posttransplant care is a key issue to increasing survival in small transplant centers. PMID- 27364328 TI - Visualization of Neuregulin 1 ectodomain shedding reveals its local processing in vitro and in vivo. AB - Neuregulin1 (NRG1) plays diverse developmental roles and is likely involved in several neurological disorders including schizophrenia. The transmembrane NRG1 protein is proteolytically cleaved and released as a soluble ligand for ErbB receptors. Such post-translational processing, referred to as 'ectodomain shedding', is thought to be crucial for NRG1 function. However, little is known regarding the regulatory mechanism of NRG1 cleavage in vivo. Here, we developed a fluorescent probe, NRG1 Cleavage Indicating SenSOR (N-CISSOR), by fusing mCherry and GFP to the extracellular and intracellular domains of NRG1, respectively. N CISSOR mimicked the subcellular localization and biochemical properties of NRG1 including cleavage dynamics and ErbB phosphorylation in cultured cells. mCherry/GFP ratio imaging of phorbol-12-myristate-13-acetate-stimulated N-CISSOR expressing HEK293T cells enabled to monitor rapid ectodomain shedding of NRG1 at the subcellular level. Utilizing N-CISSOR in zebrafish embryos revealed preferential axonal NRG1 ectodomain shedding in developing motor neurons, demonstrating that NRG1 ectodomain shedding is spatially regulated at the subcellular level. Thus, N-CISSOR will be a valuable tool for elucidating the spatiotemporal regulation of NRG1 ectodomain shedding, both in vitro and in vivo. PMID- 27364330 TI - RAPD and ISSR Marker-Based Comparative Evaluation of Genetic Diversity Among Indian Germplasms of Euryale ferox: an Aquatic Food Plant. AB - Euryale ferox Salisbury is an important aquatic food plant cultivated largely in eastern India. E. ferox is a monotypic genus, and breeding programmes have mostly relied on the variability present in the primary gene pool. Knowledge of the genetic structure of the population is limited, and there are very few reports available on the genetic diversity of E. ferox. In this study, comprehensive research on the genetic diversity of 16 germplasms of E. ferox was carried out using random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) markers. Out of 320 RAPD and 95 ISSR primers screened initially, 61 primers (40 RAPD and 21 ISSR) gave reproducible bands and were selected for further work. Amplification of the 40 RAPD primers gave 533 polymorphic bands with an average of 13.32 polymorphic bands per primer. The percentage of polymorphism ranged from 37.5 to 100, with an average of 88.3 %. The 21 ISSR primers produced 259 bands, of which 214 were polymorphic, with an average of 10.19 polymorphic bands per primer. The percentage of polymorphism using ISSR primers ranged from 50 to 100, with a mean of 82.6 %. Jaccard's coefficient ranged from 0.45 to 0.69 (RAPD), 0.50 to 0.77 (ISSR) and 0.48 to 0.71 (RAPD and ISSR). Molecular characterization of different germplasms of E. ferox not only is essential for its conservation but also can be used in further breeding programmes. PMID- 27364329 TI - Functional Impact of An ADHD-Associated DIRAS2 Promoter Polymorphism. AB - The DIRAS2 gene is coding for a small Ras GTPase with so far unknown function. In a previous study, we described the association of DIRAS2 rs1412005, as well as a haplotype containing this polymorphism and located in the promoter region of this gene with attention-deficit/hyperactivity disorder (ADHD). In the present study, we searched for rare variants within or near the DIRAS2 gene that might be associated with ADHD using next-generation sequencing. As we were not able to detect any rare variants associated with the disease, we sought to establish a functional role of DIRAS2 rs1412005 on the molecular or systems level. First, we investigated whether it has an influence on gene expression by means of a luciferase-based promoter assay. We could demonstrate that the minor risk allele goes along with the increased expression of the reporter gene. Next, we aimed to identify differences in response inhibition between risk-allele and non-risk allele carriers in children suffering from ADHD and healthy control individuals by analyzing event-related potentials in the electroencephalogram during a Go/NoGo task. Risk-allele carriers showed a changed NoGo anteriorization. Therefore, our results suggest an impact of the investigated polymorphism on the prefrontal response control in children with ADHD. These results imply that the promoter polymorphism is indeed the associated as well as in itself a causal variant. Further research is thus warranted to clarify the mechanisms linking DIRAS2 to ADHD. PMID- 27364331 TI - Functional Characterization of a Marine Bacillus Esterase and its Utilization in the Stereo-Selective Production of D-Methyl Lactate. AB - Chiral lactic acid and its ester derivatives are crucial building blocks and platforms in the generation of high value-added drugs, fine chemicals and functional materials. Optically pure D-lactic acid and its ester derivatives cannot be directly generated from fermentation and are quite expensive. Herein, we identified, heterologously expressed and functionally characterized one Bacillus esterase BSE01701 from the deep sea of the Indian Ocean. Esterase BSE01701 could enzymatically resolve inexpensive racemic methyl lactate and generate chiral D-methyl lactate. The enantiomeric excess of desired chiral D methyl lactate and the substrate conversion could reach over 99 % and 60 %, respectively, after process optimization. Notably, the addition of 60 % (v/v) organic co-solvent heptane could greatly improve both the enantiomeric excess of D-methyl lactate and the conversion. BSE01701 was a very promising marine microbial esterase in the generation of chiral chemicals in industry. PMID- 27364332 TI - Technical, Economical, and Microbiological Aspects of the Microaerobic Process on H2S Removal for Low Sulfate Concentration Wastewaters. AB - We studied the feasibility of the microaerobic process, in comparison with the traditional chemical absorption process (NaOH), on H2S removal in order to improve the biogas quality. The experiment consisted of two systems: R1, biogas from an anaerobic reactor was washed in a NaOH solution, and R2, headspace microaeration with atmospheric air in a former anaerobic reactor. The microaeration used for low sulfate concentration wastewater did not affect the anaerobic digestion, but even increased system stability. Methane production in the R2 was 14 % lower compared to R1, due to biogas dilution by the atmospheric air used. The presence of oxygen in the biogas reveals that not all the oxygen was consumed for sulfide oxidation in the liquid phase indicating mass transfer limitations. The reactor was able to rapidly recover its capacity on H2S removal after an operational failure. Bacterial and archaeal richness shifted due to changes in operational parameters, which match with the system functioning. Finally, the microaerobic system seems to be more advantageous for both technical and economical reasons, in which the payback of microaerobic process for H2S removal was 4.7 months. PMID- 27364333 TI - Raw Data Maximum Likelihood Estimation for Common Principal Component Models: A State Space Approach. AB - The specifications of state space model for some principal component-related models are described, including the independent-group common principal component (CPC) model, the dependent-group CPC model, and principal component-based multivariate analysis of variance. Some derivations are provided to show the equivalence of the state space approach and the existing Wishart-likelihood approach. For each model, a numeric example is used to illustrate the state space approach. In addition, a simulation study is conducted to evaluate the standard error estimates under the normality and nonnormality conditions. In order to cope with the nonnormality conditions, the robust standard errors are also computed. Finally, other possible applications of the state space approach are discussed at the end. PMID- 27364334 TI - Comparison of the amount of bioaccessible fumonisin B1 and B2 in maize and rice inoculated with Fusarium verticillioides (MRC 826) and determined by in vitro digestion-preliminary results. AB - In this study the occurrence of hidden fumonisin B1 (FB1) and fumonisin B2 (FB2) was analysed, on two cereal substrates (maize and rice), inoculated with Fusarium verticillioides (MRC 826), in order to determine the ratio of hidden FB1 and FB2. Two parallel methods were applied: an in vitro human digestion sample pre treatment and the routine extraction procedure, in both cases with subsequent LC MS analysis. It was found that all samples showed higher concentration of total fumonisin B1 after digestion, as compared to that of free fumonisin analysed only after extraction. The percentage of the hidden form by maize was 18.8 % (+/-2.4) for FB1 and 36.8 % (+/-3.8) for FB2, while for rice it was 32.3 % (+/-11.3) and 58.0 (+/-6.8), respectively, expressed as the proportion to total fumonisin B1, for the total dataset. Significant differences were found in the FB1 and FB2 concentration measured after the different digestion phases (saliva, gastric and duodenal) in case of both matrixes. The results are useful for human risk assessment, since both humans and animals may be exposed to markedly higher toxin load, as determined merely by conventional analytical methods. PMID- 27364335 TI - MicroRNA-130b promotes lung cancer progression via PPARgamma/VEGF-A/BCL-2 mediated suppression of apoptosis. AB - BACKGROUND: The prognosis of non-small-cell lung cancer (NSCLC) is poor yet mechanistic understanding and therapeutic options remain limited. We investigated the biological and clinical significance of microRNA-130b and its relationship with apoptosis in NSCLC. METHODS: The level of microRNA-130b in relationship with the expression of PPARgamma, VEGF-A, BCL-2 and apoptosis were analyzed in 91 lung cancer patient samples using immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay on tissue microarrays. Gain and loss-of-function studies were performed to investigate the effects of microRNA 130b, peroxisome proliferator-activated receptor gamma (PPARgamma) or vascular endothelial growth factor-A (VEGF-A) on biological functions of lung cancer cells using in vitro and in vivo approaches. RESULTS: MicroRNA-130b up-regulation conferred unfavorable prognosis of lung cancer patients. Notably, microRNA-130b targeted PPARgamma and inhibiting microRNA-130b markedly repressed proliferation, invasion and metastasis of lung cancer cells, leading to increased apoptosis. MicroRNA-130b-dependent biologic effects were due to suppression of PPARgamma that in turn activated BCL-2, the key mediator of anti-apoptosis. Administration of microRNA-130b mimic to mouse xenografts promoted tumor growth. In vitro and in vivo, miR-130b enrichment associated with down-regulation of PPARgamma, up regulation of VEGF-A and BCL-2, and decreased apoptosis. CONCLUSIONS: The present study demonstrates that microRNA-130b promotes lung cancer progression via PPARgamma/VEGF-A/BCL-2-mediated suppression of apoptosis. Targeting microRNA-130b might have remarkable therapeutic potential for lung cancer therapy. PMID- 27364336 TI - Invasive seizure monitoring in the critically-Ill brain injury patient: Current practices and a review of the literature. AB - Seizures commonly occur in a variety of serious neurological illnesses, and lead to additional morbidity and worsened outcomes. Recently, it has become clear that not all seizures in the acute brain injury setting are evident on scalp EEG. To address this, we have developed a protocol for depth electrode placement in the neuro-intensive care unit for patients in whom the clinical suspicion of occult seizures is high. In the current manuscript, we review the literature on depth EEG monitoring for ictal events in critically-ill, unconscious patients, focusing on the incidence of seizures not detected with scalp EEG in various conditions. We critically discuss evidence in support of and against treating these events that are only detectable on depth recordings. We describe additional specific scenarios in which depth EEG recordings may be helpful, including for the detection of delayed cerebral ischemia following subarachnoid hemorrhage. We then describe current techniques for bedside electrode placement. Finally, we outline potential avenues for future investigations, including the use of depth electrodes to describe circuit abnormalities in acute brain injury. PMID- 27364337 TI - [Erratum to: Multicenter trial for sudden hearing loss therapy : Planning and concept]. PMID- 27364338 TI - [Erratum to: Balloon dilatation of the Eustachian tube during middle ear surgery : Study planning and first experiences during recruitment]. PMID- 27364340 TI - In memory of Silvano Adami. PMID- 27364339 TI - [Olfactory dysfunction : Update on diagnosis and treatment]. AB - Olfactory dysfunction is a common disorder, particularly in elderly people. From the etiologic point of view, we distinguish between sinunasal and non-sinunasal causes of dysosmia. As an important early symptom of neurodegenerative disease, dysosmia is particularly relevant in the diagnosis of Parkinson's or Alzheimer's disease. In addition to complete ENT examination and olfactory testing, e.g., with "Sniffin' Sticks", modern imaging procedures, e. g. MRI, are becoming more and more important for diagnostics, prognosis, and treatment decisions. Olfactory testing in children needs to be adapted to their shorter concentration span and limited range of known olfactory stimuli. Depending on the etiology, olfactory training, antiphlogistic measures, and surgical procedures are most promising. In cases of intracranial causes of dysosmia, neurosurgeons should know and respect anatomic structures of the olfactory signal pathway, not least for long-term prognosis. PMID- 27364341 TI - Novel Compound Heterozygous Mutations in the CYP27B1 Gene Lead to Pseudovitamin D Deficient Rickets. AB - Pseudovitamin D deficiency is the consequence of a genetic defect in the CYP27B1 gene resulting in diminished or absent conversion of 25-hydroxyvitamin D3 (25 (OH)D3) into 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and leads to growth retardation and rickets, usually in the first 2 years of life. DNA obtained from human leucocytes from a patient suspected of pseudovitamin D deficiency and her healthy parents was sequenced for a genetic defect in the CYP27B1 gene. In silico analyses on the mutations were performed using online available software. The 1alpha-hydroxylase activity of the patient, her parents, and a sample derived from a mixed buffy coat of healthy blood donors was measured by culturing peripheral blood mononuclear cells with 25-(OH)D3 and measuring 1,25-(OH)2D3 production. DNA sequencing of the patient suspected of pseudovitamin D deficiency revealed compound heterozygosity in the CYP27B1 gene for a (c413G>T) mutation in exon 3 (R138L) and a (c1232G>A) mutation in exon 8 (C411Y). In silico analyses confirmed that mutations at these positions are probably damaging for the protein since the amino acids are situated in a highly conserved region. In vitro analyses showed a nearly absent 1alpha-hydroxylase activity in the patient compared to the healthy blood donors. Her healthy parents each of whom carried one of the mutations also had compromised conversion of 25-(OH)D3 into 1,25 (OH)2D3 in peripheral blood mononuclear cells, being only marginally higher than in the patient. We discovered novel compound heterozygous mutations in the CYP27B1 gene in a young girl presenting with pseudovitamin D-deficient rickets, leading to severely decreased 1,25-(OH)2D3 production. Furthermore, both heterozygous parents showed a diminished 1alpha-hydroxylase activity. PMID- 27364343 TI - First Crystal Structure for a Gold Carbene-Protein Adduct. AB - The X-ray structure of the adduct formed in the reaction between the gold N heterocyclic carbene compound Au(NHC)Cl (with NHC = 1-butyl-3-methyl-imidazole-2 ylidene) and the model protein thaumatin is reported here. The structure reveals binding of Au(NHC)(+) fragments to distinct protein sites. Notably, binding of the gold compound occurs at lysine side chains and at the N-terminal tail; the metal binds the protein after releasing Cl(-) ligand, but retaining NHC fragment. PMID- 27364342 TI - Evolution of the Marrow Adipose Tissue Microenvironment. AB - Adipocytes of the marrow adipose tissue (MAT) are distributed throughout the skeleton, are embedded in extracellular matrix, and are surrounded by cells of the hematopoietic and osteogenic lineages. MAT is a persistent component of the skeletal microenvironment and has the potential to impact local processes including bone accrual and hematopoietic function. In this review, we discuss the initial evolution of MAT in vertebrate lineages while emphasizing comparisons to the development of peripheral adipose, hematopoietic, and skeletal tissues. We then apply these evolutionary clues to define putative functions of MAT. Lastly, we explore the regulation of MAT by two major components of its microenvironment, the extracellular matrix and the nerves embedded within. The extracellular matrix and nerves contribute to both rapid and continuous modification of the MAT niche and may help to explain evolutionary conserved mechanisms underlying the coordinated regulation of blood, bone, and MAT within the skeleton. PMID- 27364344 TI - Modified Hughes procedure for reconstruction of large full-thickness lower eyelid defects following tumor resection. AB - BACKGROUND: Tarsoconjunctival flap advancement, or the Hughes procedure, is among the techniques of choice for reconstructing full-thickness lower eyelid defects so as to restore normal anatomy and function with the best possible cosmetic outcome. The purpose of this study is to report the outcome of a series of patients treated with a modified Hughes procedure following malignant tumor removal. METHODS: This retrospective study included 45 consecutive cases of modified Hughes procedures performed between January 2013 and October 2015. During Hughes flap creation an incisional plane was chosen in all cases, which left Muller's muscle attached to the superior tarsal margin, while disinserting the levator aponeurosis. All cases were grouped according to the horizontal length of the lower lid defect to be reconstructed, as well as to the type of anterior lamella reconstruction (free graft vs. inferiorly based advancement flap). Grouped data were compared for the rate of surgical success, defined as achievement of normal lid function and satisfactory cosmesis without needing further surgical interventions, and for the frequency of specific complications. RESULTS: Surgical success was achieved in 39 cases (87 %). The remaining cases required additional surgery for minor complications including lower-lid ectropion (4 %), pyogenic granuloma (4 %), or lower lid margin hypertrophy (2 %). Donor site complications were not detected apart from one case of mild entropion with focal trichiasis. No case of premature flap rupture was seen. Neither the horizontal length of the lower lid defect (p = 0.489), nor the type of anterior lamella reconstruction (p = 0.349) significantly affected the surgical success. Particularly, there was no increased onset of lower-lid ectropion among patients receiving an advancement flap. CONCLUSIONS: The modified Hughes procedure remains a well-suited technique for reconstructing lower eyelid defects involving up to 100 % of the horizontal lid length. Leaving Muller's muscle attached to the Hughes flap might prevent premature flap dehiscence without increasing the frequency of upper lid retractions in turn. Whether using a free skin graft or a skin-muscle advancement flap for anterior lamella reconstruction, seems to be insignificant for the functional-aesthetical outcome. PMID- 27364345 TI - The Moderating Role of Anxiety in the Associations of Callous-Unemotional Traits with Self-Report and Laboratory Measures of Affective and Cognitive Empathy. AB - In a sample of detained male adolescents (n = 107; Mean age = 15.50; SD = 1.30), we tested whether anxiety moderated the association of CU traits with self-report and computerized measures of affective (emotional reactivity) and cognitive (affective facial recognition and Theory of Mind [ToM]) empathy. Hierarchical regression analyses revealed that CU traits were negatively associated with self reports of affective empathy and this association was not moderated by level of anxiety. Significant interactions revealed that CU traits were negatively associated with cognitive empathy (self-report) only at high levels of anxiety, whereas CU traits were positively associated with cognitive empathy on the ToM task only at low levels of anxiety. CU traits were also associated with greater fear recognition accuracy at low levels of anxiety. Implications for understanding and treating different variants of CU traits (i.e., primary and secondary) are discussed. PMID- 27364347 TI - Abortion in Islamic Ethics, and How it is Perceived in Turkey: A Secular, Muslim Country. AB - Abortion is among the most widely discussed concepts of medical ethics. Since the well-known ethical theories have emerged from Western world, the position of Islamic ethics regarding main issues of medical ethics has been overlooked. Muslims constitute a considerable amount of world population. Turkish Republic is the only Muslim country ruled with secular democracy and one of the three Muslim countries where abortion is legalized. The first aim of this paper is to present discussions on abortion in Islamic ethics in the context of major ethical concepts; the legal status of the fetus, respect for life and the right not to be born. The second aim is to put forth Turkey's present legislation about abortion in the context of Islamic ethical and religious aspects. PMID- 27364346 TI - Comparing the CASI-4R and the PGBI-10 M for Differentiating Bipolar Spectrum Disorders from Other Outpatient Diagnoses in Youth. AB - We compared 2 rating scales with different manic symptom items on diagnostic accuracy for detecting pediatric bipolar spectrum disorder (BPSDs) in outpatient mental health clinics. Participants were 681 parents/guardians of eligible children (465 male, mean age = 9.34) who completed the Parent General Behavior Inventory-10-item Mania (PGBI-10 M) and mania subscale of the Child and Adolescent Symptom Inventory-Revised (CASI-4R). Diagnoses were based on KSADS interviews with parent and youth. Receiver operating characteristic (ROC) analyses and diagnostic likelihood ratios (DLRs) determined discriminative validity and provided clinical utility, respectively. Logistic regressions tested for incremental validity in the CASI-4R mania subscale and PGBI-10 M in predicting youth BPSD status above and beyond demographic and common diagnostic comorbidities. Both CASI-4R and PGBI-10 M scales significantly distinguished BPSD (N = 160) from other disorders (CASI-4R: Area under curve (AUC) = .80, p < 0.0005; PGBI-10 M: AUC = 0.79, p < 0.0005) even though scale items differed. Both scales performed equally well in differentiating BPSDs (Venkatraman test p > 0.05). Diagnostic likelihood ratios indicated low scores on either scale (CASI: 0 5; PGBI-10 M: 0-6) cut BPSD odds to 1/5 of those with high scores (CASI DLR- = 0.17; PGBI-10 M DLR- = 0.18). High scores on either scale (CASI: 14+; PGBI-10 M: 20+) increased BPSD odds about fourfold (CASI DLR+ = 4.53; PGBI-10 M DLR+ = 3.97). Logistic regressions indicated the CASI-4R mania subscale and PGBI-10 M each provided incremental validity in predicting youth BPSD status. The CASI-4R is at least as valid as the PGBI-10 M to help identify BPSDs, and can be considered as part of an assessment battery to screen for pediatric BPSDs. PMID- 27364348 TI - Bone morphogenetic protein-binding endothelial regulator of liver sinusoidal endothelial cells induces iron overload in a fatty liver mouse model. AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is frequently accompanied by iron overload. However, because of the complex hepcidin-regulating molecules, the molecular mechanism underlying iron overload remains unknown. To identify the key molecule involved in NAFLD-associated iron dysregulation, we performed whole RNA sequencing on the livers of obese mice. METHODS: Male C57BL/6 mice were fed a regular or high-fat diet for 16 or 48 weeks. Internal iron was evaluated by plasma iron, ferritin or hepatic iron content. Whole-RNA sequencing was performed by transcriptome analysis using semiconductor high-throughput sequencer. Mouse liver tissues or isolated hepatocytes and sinusoidal endothelial cells were used to assess the expression of iron-regulating molecules. RESULTS: Mice fed a high fat diet for 16 weeks showed excess iron accumulation. Longer exposure to a high fat diet increased hepatic fibrosis and intrahepatic iron accumulation. A pathway analysis of the sequencing data showed that several inflammatory pathways, including bone morphogenetic protein (BMP)-SMAD signaling, were significantly affected. Sequencing analysis showed 2314 altered genes, including decreased mRNA expression of the hepcidin-coding gene Hamp. Hepcidin protein expression and SMAD phosphorylation, which induces Hamp, were found to be reduced. The expression of BMP-binding endothelial regulator (BMPER), which inhibits BMP-SMAD signaling by binding BMP extracellularly, was up-regulated in fatty livers. In addition, immunohistochemical and cell isolation analyses showed that BMPER was primarily expressed in the liver sinusoidal endothelial cells (LSECs) rather than hepatocytes. CONCLUSIONS: BMPER secretion by LSECs inhibits BMP-SMAD signaling in hepatocytes and further reduces hepcidin protein expression. These intrahepatic molecular interactions suggest a novel molecular basis of iron overload in NAFLD. PMID- 27364351 TI - A full-dimensional model of ozone forming reaction: the absolute value of the recombination rate coefficient, its pressure and temperature dependencies. AB - Rigorous calculations of scattering resonances in ozone are carried out for a broad range of rotational excitations. The accurate potential energy surface of Dawes is adopted, and a new efficient method for calculations of ro-vibrational energies, wave functions and resonance lifetimes is employed (which uses hyper spherical coordinates, the sequential diagonalization/truncation approach, grid optimization and complex absorbing potential). A detailed analysis is carried out to characterize distributions of resonance energies and lifetimes, their rotational/vibrational content and their positions with respect to the centrifugal barrier. Emphasis is on the contribution of these resonances to the recombination process that forms ozone. It is found that major contributions come from localized resonances at energies near the top of the barrier. Delocalized resonances at higher energies should also be taken into account, while very narrow resonances at low energies (trapped far behind the centrifugal barrier) should be treated as bound states. The absolute value of the recombination rate coefficient, its pressure and temperature dependencies are obtained using the energy-transfer model developed in the earlier work. Good agreement with experimental data is obtained if one follows the suggestion of Troe, who argued that the energy transfer mechanism of recombination is responsible only for 55% of the recombination rate (with the remaining 45% coming from the competing chaperon mechanism). PMID- 27364350 TI - A novel spontaneous mutation of BCAR3 results in extrusion cataracts in CF#1 mouse strain. AB - A substrain of mice originating from the CF#1 strain (an outbred colony) reared at Osaka Prefecture University (CF#1/lr mice) develops cataracts beginning at 4 weeks of age. Affected mice were fully viable and fertile and developed cataracts by 14 weeks of age. Histologically, CF#1/lr mice showed vacuolation of the lens cortex, swollen lens fibers, lens rupture and nuclear extrusion. To elucidate the mode of inheritance, we analyzed heterozygous mutant hybrids generated from CF#1/lr mice and wild-type BALB/c mice. None of the heterozygous mutants were affected, and the ratio of affected to unaffected mice was 1:3 among the offspring of the heterozygous mutants. For the initial genome-wide screening and further mapping, we used affected progeny of CF#1/lr * (CF#1/lr * BALB/c) mice. We concluded that the cataracts in CF#1/lr mice are inherited through an autosomal recessive mutation and that the mutant gene is located on mouse chromosome 3 between D3Mit79 and D3Mit216. In this region, we identified 8 genes associated with ocular disease. All 8 genes were sequenced and a novel point mutation (1 bp insertion of cytosine) in exon 7 of the Bcar3 gene was identified. This mutation produced a premature stop codon and a truncated protein. In conclusion, we have identified the first spontaneous mutation in the Bcar3 gene associated with lens extrusion cataracts. This novel cataract model may provide further knowledge of the molecular biology of cataractogenesis and the function of the BCAR3 protein. PMID- 27364352 TI - When to eat? The influence of circadian rhythms on metabolic health: are animal studies providing the evidence? AB - As obesity and metabolic diseases rise, there is need to investigate physiological and behavioural aspects associated with their development. Circadian rhythms have a profound influence on metabolic processes, as they prepare the body to optimise energy use and storage. Moreover, food-related signals confer temporal order to organs involved in metabolic regulation. Therefore food intake should be synchronised with the suprachiasmatic nucleus (SCN) to elaborate efficient responses to environmental challenges. Human studies suggest that a loss of synchrony between mealtime and the SCN promotes obesity and metabolic disturbances. Animal research using different paradigms has been performed to characterise the effects of timing of food intake on metabolic profiles. Therefore the purpose of the present review is to critically examine the evidence of animal studies, to provide a state of the art on metabolic findings and to assess whether the paradigms used in rodent models give the evidence to support a 'best time' for food intake. First we analyse and compare the current findings of studies where mealtime has been shifted out of phase from the light-dark cycle. Then, we analyse studies restricting meal times to different moments within the active period. So far animal studies correlate well with human studies, demonstrating that restricting food intake to the active phase limits metabolic disturbances produced by high-energy diets and that eating during the inactive/sleep phase leads to a worse metabolic outcome. Based on the latter we discuss the missing elements and possible mechanisms leading to the metabolic consequences, as these are still lacking. PMID- 27364349 TI - Unraveling the message: insights into comparative genomics of the naked mole-rat. AB - Animals have evolved to survive, and even thrive, in different environments. Genetic adaptations may have indirectly created phenotypes that also resulted in a longer lifespan. One example of this phenomenon is the preternaturally long lived naked mole-rat. This strictly subterranean rodent tolerates hypoxia, hypercapnia, and soil-based toxins. Naked mole-rats also exhibit pronounced resistance to cancer and an attenuated decline of many physiological characteristics that often decline as mammals age. Elucidating mechanisms that give rise to their unique phenotypes will lead to better understanding of subterranean ecophysiology and biology of aging. Comparative genomics could be a useful tool in this regard. Since the publication of a naked mole-rat genome assembly in 2011, analyses of genomic and transcriptomic data have enabled a clearer understanding of mole-rat evolutionary history and suggested molecular pathways (e.g., NRF2-signaling activation and DNA damage repair mechanisms) that may explain the extraordinarily longevity and unique health traits of this species. However, careful scrutiny and re-analysis suggest that some identified features result from incorrect or imprecise annotation and assembly of the naked mole-rat genome: in addition, some of these conclusions (e.g., genes involved in cancer resistance and hairlessness) are rejected when the analysis includes additional, more closely related species. We describe how the combination of better study design, improved genomic sequencing techniques, and new bioinformatic and data analytical tools will improve comparative genomics and ultimately bridge the gap between traditional model and nonmodel organisms. PMID- 27364354 TI - BMJ Awards South Asia 2016: Nominate a healthcare champion today. PMID- 27364353 TI - Long-term production of BDNF and NT-3 induced by A91-immunization after spinal cord injury. AB - BACKGROUND: After spinal cord (SC)-injury, a non-modulated immune response contributes to the damage of neural tissue. Protective autoimmunity (PA) is a T cell mediated, neuroprotective response induced after SC-injury. Immunization with neural-derived peptides (INDP), such as A91, has shown to promote-in vitro the production of neurotrophic factors. However, the production of these molecules has not been studied at the site of injury. RESULTS: In order to evaluate these issues, we performed four experiments in adult female Sprague Dawley rats. In the first one, brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) concentrations were evaluated at the site of lesion 21 days after SC-injury. BDNF and NT-3 were significantly increased in INDP-treated animals. In the second experiment, proliferation of anti-A91 T cells was assessed at chronic stages of injury. In this case, we found a significant proliferation of these cells in animals subjected to SC-injury + INDP. In the third experiment, we explored the amount of BDNF and NT3 at the site of injury in the chronic phase of rats subjected to either SC-contusion (SCC; moderate or severe) or SC transection (SCT; complete or incomplete). The animals were treated with INDP immediately after injury. Rats subjected to moderate contusion or incomplete SCT showed significantly higher levels of BDNF and NT-3 as compared to PBS-immunized ones. In rats with severe SCC and complete SCT, BDNF and NT-3 concentrations were barely detected. Finally, in the fourth experiment we assessed motor function recovery in INDP-treated rats with moderate SC-injury. Rats immunized with A91 showed a significantly higher motor recovery from the first week and up to 4 months after SC-injury. CONCLUSIONS: The results of this study suggest that PA boosted by immunization with A91 after moderate SC-injury can exert its benefits even at chronic stages, as shown by long-term production of BDNF and NT-3 and a substantial improvement in motor recovery. PMID- 27364356 TI - Fibula flap harvest: How leg selection impacts inset for mandible defects. PMID- 27364355 TI - High glucose-induced cytoplasmic translocation of Dnmt3a contributes to CTGF hypo methylation in mesangial cells. AB - Connective tissue growth factor (CTGF) plays an essential role in the pathogenesis of diabetic nephropathy and we have previously identified that high glucose induced the expression of CTGF by decreasing DNA methylation. The aim of the present study was to investigate the underlying mechanisms of the high glucose-induced CTGF hypo-methylation. Human glomerular mesangial cells (hMSCs) were treated with low glucose (5 mM), mannitol (30 mM) or high glucose (30 mM) respectively. Immunofluorescence staining, real-time quantitative PCR and western blotting were performed to determine the subcellular distribution and expression of CTGF and Dnmt3a. ChIP-PCR assay was applied to investigate the capability of Dnmt3a to bind the CpG island of CTGF. Our results showed that high glucose induced both mRNA and protein expressions of CTGF, and led to increased cytoplasmic translocation of Dnmt3a in cultured hMSCs. The nuclear Dnmt3a protein was significantly reduced after high glucose treatment, although the expression of total Dnmt3a protein was not altered. We further discovered that ERK/MAPK signalling contributed to the high glucose-induced cytoplasmic translocation of Dnmt3a. Consequently, less Dnmt3a protein was bound to the CpG island of CTGF promoter, which induced an increase in CTGF expression by epigenetic regulation in the presence of high glucose. In conclusion, high glucose induces cytoplasmic translocation of Dnmt3a, possibly through activating ERK/MAPK signalling pathway, which contributes to the decreased binding of Dnmt3a on CTGF promoter and the subsequent CTGF hypo-methylation in diabetic nephropathy. PMID- 27364357 TI - Ultrasensitive multiplex optical quantification of bacteria in large samples of biofluids. AB - Efficient treatments in bacterial infections require the fast and accurate recognition of pathogens, with concentrations as low as one per milliliter in the case of septicemia. Detecting and quantifying bacteria in such low concentrations is challenging and typically demands cultures of large samples of blood (~1 milliliter) extending over 24-72 hours. This delay seriously compromises the health of patients. Here we demonstrate a fast microorganism optical detection system for the exhaustive identification and quantification of pathogens in volumes of biofluids with clinical relevance (~1 milliliter) in minutes. We drive each type of bacteria to accumulate antibody functionalized SERS-labelled silver nanoparticles. Particle aggregation on the bacteria membranes renders dense arrays of inter-particle gaps in which the Raman signal is exponentially amplified by several orders of magnitude relative to the dispersed particles. This enables a multiplex identification of the microorganisms through the molecule-specific spectral fingerprints. PMID- 27364359 TI - Plant growth promotion, metabolite production and metal tolerance of dark septate endophytes isolated from metal-polluted poplar phytomanagement sites. AB - Numerous studies address the distribution and the diversity of dark septate endophytes (DSEs) in the literature, but little is known about their ecological role and their effect on host plants, especially in metal-polluted soils. Seven DSE strains belonging to Cadophora, Leptodontidium, Phialophora and Phialocephala were isolated from roots of poplar trees from metal-polluted sites. All strains developed on a wide range of carbohydrates, including cell-wall-related compounds. The strains evenly colonized birch, eucalyptus and ryegrass roots in re-synthesis experiments. Root and shoot growth promotion was observed and was both plant and strain dependent. Two Phialophora and Leptodontidium strains particularly improved plant growth. However, there was no correlation between the level of root colonization by DSEs and the intensity of growth promotion. All strains produced auxin and six also stimulated plant growth through the release of volatile organic compounds (VOCs). SPME-GC/MS analyses revealed four major VOCs emitted by Cadophora and Leptodontidium The strains exhibited growth at high concentrations of several metals. The ability of metal-resistant DSE strains to produce both soluble and volatile compounds for plant growth promotion indicates interesting microbial resources with high potential to support sustainable production of bioenergy crops within the context of the phytomanagement of metal contaminated sites. PMID- 27364360 TI - Effects of endophytic fungi on the ash dieback pathogen. AB - While Hymenoscyphus fraxineus causes dieback of the European ash (Fraxinus excelsior), flowering ash (F. ornus) appears resistant to the pathogen. To date, contributions of endophytic fungi to host resistance are unknown. The following hypotheses were tested: (i) endophytic fungi enhance the resistance of F. excelsior to the pathogen; (ii) resistance of F. ornus relies on its community of endophytic fungi. Two experiments were performed. (i) The effect of exudates of ash endophytes on the germination rate of H. fraxineus ascospores was studied in vitro Isolates of abundant Fraxinus leaf endophytes, such as Venturia fraxini, Paraconiothyrium sp., Boeremia exigua, Kretzschmaria deusta and Neofabraea alba inhibited ascospore germination. (ii) Ash seedlings inoculated in a climate chamber, with fungi sporulating on the previous year's leaf litter, were exposed to natural infections by the pathogen present in the forest. Non-inoculated seedlings were used as controls. Venturia spp. dominated the inoculated endophyte 'communities'. Subsequent exposure to H. fraxineus led to infection of F. excelsior leaves by the pathogen, but no differences in health status between pre inoculated and non-inoculated seedlings were detected. Fraxinus ornus leaves experienced a low infection rate, independent of their colonization by endophytic fungi. These results did not support either hypothesis. PMID- 27364358 TI - Proteomic Screening and Lasso Regression Reveal Differential Signaling in Insulin and Insulin-like Growth Factor I (IGF1) Pathways. AB - Insulin and insulin-like growth factor I (IGF1) influence cancer risk and progression through poorly understood mechanisms. To better understand the roles of insulin and IGF1 signaling in breast cancer, we combined proteomic screening with computational network inference to uncover differences in IGF1 and insulin induced signaling. Using reverse phase protein array, we measured the levels of 134 proteins in 21 breast cancer cell lines stimulated with IGF1 or insulin for up to 48 h. We then constructed directed protein expression networks using three separate methods: (i) lasso regression, (ii) conventional matrix inversion, and (iii) entropy maximization. These networks, named here as the time translation models, were analyzed and the inferred interactions were ranked by differential magnitude to identify pathway differences. The two top candidates, chosen for experimental validation, were shown to regulate IGF1/insulin induced phosphorylation events. First, acetyl-CoA carboxylase (ACC) knock-down was shown to increase the level of mitogen-activated protein kinase (MAPK) phosphorylation. Second, stable knock-down of E-Cadherin increased the phospho-Akt protein levels. Both of the knock-down perturbations incurred phosphorylation responses stronger in IGF1 stimulated cells compared with insulin. Overall, the time-translation modeling coupled to wet-lab experiments has proven to be powerful in inferring differential interactions downstream of IGF1 and insulin signaling, in vitro. PMID- 27364361 TI - Granuloma faciale successfully treated with ingenol mebutate. AB - Granuloma faciale (GF) is a rare chronic inflammatory dermatosis of unknown etiology, characterized by leukocitoclastic vasculitis usually occurring on the face. We report a case of 60-years-old man with 3 year history of multiple actinic keratoses (AK) and persistent asymptomatic erythematous papules and plaques located over his left temporal region and the cheek: histopathology was consistent with GF. Herein we describe the successful treatment of the lesion with ingenol mebutate 0.015% gel focusing on the clinical, dermoscopic and histopathological findings of GF both before and after treatment. PMID- 27364363 TI - Endocannabinoid System in Neurological Disorders. AB - BACKGROUND: Several studies support the evidence that the endocannabinoid system and cannabimimetic drugs might have therapeutic potential in numerous pathologies. These pathologies range from neurological disorders, atherosclerosis, stroke, cancer to obesity/metabolic syndrome and others. METHODS: In this paper we review the endocannabinoid system signaling and its alteration in neurodegenerative disorders like multiple sclerosis, Alzheimer's disease, Parkinson's disease and Huntington's disease and discuss the main findings about the use of cannabinoids in the therapy of these pathologies. RESULTS: Despite different etiologies, neurodegenerative disorders exhibit similar mechanisms like neuro-inflammation, excitotoxicity, deregulation of intercellular communication, mitochondrial dysfunction and disruption of brain tissue homeostasis. Current treatments ameliorate the symptoms but are not curative. Interfering with the endocannabinoid signaling might be a valid therapeutic option in neuro-degeneration. To this aim, pharmacological intervention to modulate the endocannabinoid system and the use of natural and synthetic cannabimimetic drugs have been assessed. CB1 and CB2 receptor signaling contributes to the control of Ca2+ homeostasis, trophic support, mitochondrial activity, and inflammatory conditions. CONCLUSION: Several studies and patents suggest that the endocannabinoid system has neuro-protective properties and might be a target in neurodegenerative diseases. PMID- 27364362 TI - Propofol attenuated liver transplantation-induced acute lung injury via connexin43 gap junction inhibition. AB - BACKGROUND: Postoperative acute lung injury (ALI) is a severe complication after liver transplantation, which influences patient survival rate obviously. However, its mechanisms are unclear and effective therapies are still lacking. The current study focused on effects of propofol on liver transplantation-induced ALI and whether its underlying mechanism was relative with connexin43 (Cx43) alternation. The authors postulated that endotoxin induced enhancement of Cx43 gap junction (GJ) plays a critical role in mediating post liver transplantation ALI and that pretreatment with the anesthetic propofol, known to inhibit gap junction, can confer effective protection. METHODS: Male Sprague-Dawley rats underwent autologous orthotopic liver transplantation (AOLT) in the absence or presence of treatments with the selective Cx43 inhibitor, enanthol (0.1 mg/kg) and propofol (50 mg/kg), a commonly used anesthetic in clinical anesthesia. In vitro study, BEAS-2B cells, a kind of lung epithelial cell line expressing Cx43, exposed to lipopolysaccharide (LPS), which mainly contributed to ALI. Function of Cx43 GJ was regulated by Cx43 specific inhibitors, gap26 (300 MUM) or enhancer, retinoic acid (10 MUM) and two specific siRNAs. RESULTS: Compared with the sham group, AOLT results in ALI obviously with plasma endotoxin increase. Cx43 inhibition decreased ALI through inflammatory reaction reduction. In vitro studies, LPS induced BEAS-2B cells damage was attenuated by Cx43 function inhibition, but amplified by enhancement. Another important finding was propofol reduced Cx43 function and protected against LPS-mediated BEAS-2B cells damage or AOLT-induced ALI, mechanisms of which were also associated with inflammatory reaction decrease. CONCLUSION: Cx43 plays a vital role in liver transplantation-induced ALI. Propofol decreased Cx43 function and protected against ALI in vivo and in vitro. This finding provide a new basis for targeted intervention of organ protection in liver transplantation, even in other kinds of operations. PMID- 27364364 TI - Divergence of gastropod life history in contrasting thermal environments in a geothermal lake. AB - Experiments using natural populations have provided mixed support for thermal adaptation models, probably because the conditions are often confounded with additional environmental factors like seasonality. The contrasting geothermal environments within Lake Myvatn, northern Iceland, provide a unique opportunity to evaluate thermal adaptation models using closely located natural populations. We conducted laboratory common garden and field reciprocal transplant experiments to investigate how thermal origin influences the life history of Radix balthica snails originating from stable cold (6 degrees C), stable warm (23 degrees C) thermal environments or from areas with seasonal temperature variation. Supporting thermal optimality models, warm-origin snails survived poorly at 6 degrees C in the common garden experiment and better than cold-origin and seasonal-origin snails in the warm habitat in the reciprocal transplant experiment. Contrary to thermal adaptation models, growth rate in both experiments was highest in the warm populations irrespective of temperature, indicating cogradient variation. The optimal temperatures for growth and reproduction were similar irrespective of origin, but cold-origin snails always had the lowest performance, and seasonal-origin snails often performed at an intermediate level compared to snails originating in either stable environment. Our results indicate that central life-history traits can differ in their mode of evolution, with survival following the predictions of thermal optimality models, whereas ecological constraints have shaped the evolution of growth rates in local populations. PMID- 27364365 TI - Instrumentation for Reliably Determining Porous Silicon Photoluminescence Responses to Gaseous Analyte Vapors. AB - We report new instrumentation for rapidly and reliably measuring the temperature dependent photoluminescence response from porous silicon as a function of analyte vapor concentration. The new system maintains the porous silicon under inert conditions and it allows on-the-fly steady-state and time-resolved photoluminescence intensity and hyper-spectral measurements between 293 K and 450 K. The new system yields reliable data at least 100-fold faster in comparison to previous instrument platforms. PMID- 27364366 TI - Transmission Raman Measurements Using a Spatial Heterodyne Raman Spectrometer (SHRS). AB - A spatial heterodyne Raman spectrometer (SHRS) was used to measure transmission Raman spectra of highly scattering compounds. Transmission Raman spectral intensities of ibuprofen were only 2.4 times lower in intensity than backscatter Raman spectra. The throughput was about eight times higher than an f/1.8 dispersive spectrometer, and the width of the area viewed was found to be seven to nine times higher, using 50.8 mm and 250 mm focal length collection lenses. However, the signal-to-noise (S/N) ratio was two times lower for the SHRS than the f/1.8 dispersive spectrometer, apparently due to high levels of stray light. PMID- 27364367 TI - Cavity Ring-Down Absorption of O2 in Air as a Temperature Sensor for an Open and a Cryogenic Optical Cavity. AB - The A-band of oxygen has been measured at low resolution at temperatures between 90 K and 373 K using the phase shift cavity ring down (PS-CRD) technique. For temperatures between 90 K and 295 K, the PS-CRD technique presented here involves an optical cavity attached to a cryostat. The static cell and mirrors of the optical cavity are all inside a vacuum chamber at the same temperature of the cryostat. The temperature of the cell can be changed between 77 K and 295 K. For temperatures above 295 K, a hollow glass cylindrical tube without windows has been inserted inside an optical cavity to measure the temperature of air flowing through the tube. The cavity consists of two highly reflective mirrors which are mounted parallel to each other and separated by a distance of 93 cm. In this experiment, air is passed through a heated tube. The temperature of the air flowing through the tube is determined by measuring the intensity of the oxygen absorption as a function of the wavenumber. The A-band of oxygen is measured between 298 K and 373 K, with several air flow rates. To obtain the temperature, the energy of the lower rotational state for seven selected rotational transitions is linearly fitted to a logarithmic function that contains the relative intensity of the rotational transition, the initial and final rotational quantum numbers, and the energy of the transition. Accuracy of the temperature measurement is determined by comparing the calculated temperature from the spectra with the temperature obtained from a calibrated thermocouple inserted at the center of the tube. This flowing air temperature sensor will be used to measure the temperatures of cooling air at the input (cold air) and output (hot air) after cooling the blades of a laboratory gas turbine. The results could contribute to improvements in turbine blade cooling design. PMID- 27364368 TI - Three-dimensional fracture pattern analysis of the Obwegeser and Dal Pont bilateral sagittal split osteotomy. AB - The Obwegeser and Dal Pont modification of the bilateral sagittal split osteotomy (BSSO) is a well-established procedure in orthognathic surgery. The purpose of this retrospective study was to analyze the actual fracture patterns achieved with BSSO by Obwegeser and Dal Pont modification using postoperative cone beam computed tomography (CBCT) datasets from 100 patients. A total of 200 split osteotomies were assessed, which could be categorized into nine different split patterns. Only one of the observed split fractures (0.5%) followed exactly the fracture line described by Obwegeser and Dal Pont, whereas 40% followed the fracture line according to the Hunsuck and Epker modification and 13.5% were seen as unfavourable splits mainly running over the buccal plate. A significant correlation was found between unfavourable buccal splits and both horizontal osteotomies reaching the buccal surface at the dorsal ramus (P=0.001) and a vertical caudal bone cut end at the corpus with a buccal position (P<0.001). These results show that a complete antero-posterior horizontal osteotomy at the mandibular ramus does not lead to the intended fracture pattern, which rebuts the argument of a greater amount of bony overlap using the Obwegeser and Dal Pont modification. PMID- 27364369 TI - Guided bone regeneration using individualized ceramic sheets. AB - Guided bone regeneration (GBR) describes the use of membranes to regenerate bony defects. A membrane for GBR needs to be biocompatible, cell-occlusive, non-toxic, and mouldable, and possess space-maintaining properties including stability. The purpose of this pilot study was to describe a new method of GBR using individualized ceramic sheets to perfect bone regeneration prior to implant placement; bone regeneration was assessed using traditional histology and three dimensional (3D) volumetric changes in the bone and soft tissue. Three patients were included. After full-thickness flap reflection, the individualized ceramic sheets were fixed. The sites were left to heal for 7 months. All patients were evaluated preoperatively and at 7 months postoperative using cone beam computed tomography and 3D optical equipment. Samples of the regenerated bone and soft tissue were collected and analyzed. The bone regenerated in the entire interior volume of all sheets. Bone biopsies revealed newly formed trabecular bone with a lamellar structure. Soft tissue biopsies showed connective tissue with no signs of an inflammatory response. This was considered to be newly formed periosteum. Thus ceramic individualized sheets can be used to regenerate large volumes of bone in both vertical and horizontal directions independent of the bone defect and with good biological acceptance of the material. PMID- 27364370 TI - Maternal biomarkers of methylation status and non-syndromic orofacial cleft risk: a meta-analysis. AB - Animal models have shown evidence of the role of maternal methyl donor status and its metabolism (one-carbon metabolism) in normal embryonic maxillofacial development. Nevertheless, studies in humans have shown conflicting results for the association of maternal methylation status biomarkers in the aetiology of the main craniofacial birth defects: non-syndromic orofacial clefts (NSOFCs). The aim of this study was to perform a meta-analysis assessing the relationship between maternal levels of methylation status biomarkers (plasma and erythrocyte folates and plasma vitamin B12 and homocysteine) and the risk of NSOFCs. A literature search of the conventional and grey medical-scientific databases identified 12 studies considering these variables. Based on standardized differences between means among cases and controls (Cohen's d test), evidence was found of an association only with high plasma homocysteine (d=0.37; P=0.026) when single effects were pooled. In addition to its usefulness as a marker of poor methyl donor intake and/or metabolism, homocysteine appears to have a teratogenic effect. Although the results are based on a relatively small number of reports and/or studies of small sample sizes showing between-study heterogeneity, these problems were resolved by including an additional analysis. Therefore these findings constitute a real contribution towards explaining the complex aetiology of orofacial clefts. PMID- 27364371 TI - Modified alar base cinch suture fixation at the bilateral lower border of the piriform rim after a maxillary Le Fort I osteotomy. AB - Classic cinch suture narrowing of the nasal alar base by medially suturing the bilateral nasolabial soft tissue with one long suture has a limited effect. The modified cinch method described in the present study anchors non-absorbable sutures to the bilateral lower border of the piriform rim and provides optimal direction, position, and stability. The sutures can be shortened and the strength kept stable while the surgical wounds heal. Separate bilateral sutures can also reduce interference and distortion from nasotracheal intubation and make the nasolabial profile more symmetrical. Seventeen consecutive cases of maxillary Le Fort I osteotomy were analyzed. The nasal and alar base width changes were 0.4+/ 1.2mm and 0.1+/-1.1mm, respectively, and the widening rate was only 1.1%. Compared with the results of other studies, postoperative nasal flaring was well controlled using the modified cinch suture anchored to the bilateral lower border of the piriform rim described in this study. PMID- 27364372 TI - Is arthrocentesis plus platelet-rich plasma superior to arthrocentesis plus hyaluronic acid for the treatment of temporomandibular joint osteoarthritis: a randomized clinical trial. AB - A randomized clinical trial was implemented in adult patients with temporomandibular joint osteoarthritis (TMJ OA). The sample comprised 49 osteoarthritic joints in 31 consecutive patients. Patients were divided randomly into two groups according to the treatment technique applied: the platelet-rich plasma (PRP) group patients underwent initial arthrocentesis plus PRP injection and then four consecutive PRP injections; the hyaluronic acid (HA) group patients underwent one session of arthrocentesis plus HA injection. The predictor variable was the treatment technique. The outcome variables included visual analogue scale (VAS) evaluations and maximum inter-incisal opening (MIO) measurements. Outcome variables were recorded preoperatively and at 12 months postoperative. Descriptive and bivariate statistics were computed and significance was set at P<0.05. The PRP group included 32 joints in 18 subjects, and the HA group included 17 joints in 13 subjects. No statistically significant difference was observed between the groups for any of the changes in VAS parameters or MIO measurements. Both treatment techniques resulted in significant clinical improvements in all VAS parameters and painless MIO. These findings suggest that arthrocentesis plus PRP injections is not superior to arthrocentesis plus a single HA injection; thus PRP injection should not be considered as the first line treatment. Arthrocentesis plus HA injection would appear to be more acceptable for patients. PMID- 27364373 TI - Serotonin and melatonin secretion in postmenopausal women with eating disorders. AB - INTRODUCTION: Postmenopausal women manifest emotional disorders associated with an increase in appetite. The aim of the study was to assess the serotonin and melatonin secretion and metabolism in postmenopausal women in relation to eating disorders. MATERIAL AND METHODS: Sixty postmenopausal women and 30 women without hormonal disturbances were enrolled into the study and divided into three groups: group I (control) - women without menstrual disorders, group II - postmenopausal women without appetite disorders and change in body weight, and group III - postmenopausal women with increased appetite and weight gain. Serum melatonin, serotonin, urinary 6-sulfatoxymelatonin (aMT6s), and 5-hydroxyindoleacetic acid (5-HIAA) excretion were measured. RESULTS: Serum serotonin and melatonin levels in groups II and III were lower compared to group I. Urinary 5-HIAA and aMT6s excretion was lower in overweight women. In group III the correlation between the serum level of serotonin, melatonin, and BMI was negative; a high statistical significance was found between BMI and urinary aMT6s excretion. CONCLUSIONS: Melatonin supplementation and use of drugs modulating the serotonin homeostasis together with female hormones have a beneficial effect in complex treatment of disorders of eating in postmenopausal women. (Endokrynol Pol 2016; 67 (3): 299 304). PMID- 27364374 TI - Insulin therapy - new directions of research. AB - Insulin therapy is the most effective method of lowering blood glucose. Over 100 years have passed the studies for the optimisation of insulin action. To date, subcutaneous insulin administration has been the basic route of insulin delivery. The search for insulin therapy is simultaneously conducted in the following directions: the optimisation of insulin action, automatisation, and the decrease in the invasiveness of insulin delivery methods. The optimisation of insulin action has led to the discovery of ultra-rapid-acting human insulin analogues, ultra-long-acting human insulin analogues, and biosimilar insulin. Automatisation referred to the "artificial pancreas" and closing the loop system in insulin pump therapy. The decrease in the invasiveness of insulin delivery methods is focused on alternative routes of insulin administration. (Endokrynol Pol 2016; 67 (3): 314-324). PMID- 27364375 TI - Low versus high dialysate calcium concentration in alternate night nocturnal hemodialysis: A randomized controlled trial. AB - INTRODUCTION: Higher calcium dialysate is recommended for quotidian nocturnal hemodialysis (NHD) (>=6 nights/week) to maintain bone health. It is unclear what the optimal calcium dialysate concentration should be for alternate night NHD. We aimed to determine the effect of low calcium (LC) versus high calcium (HC) dialysate on cardiovascular and bone parameters in this population. METHODS: A randomized controlled trial where participants were randomized to LC (1.3 mmol/L, n = 24) or HC dialysate (1.6 or 1.75 mmol/L, n = 26). Primary outcome was change in mineral metabolism markers. Secondary outcomes included change in vascular calcification (VC) scores [CT abdominal aorta (AA) and superficial femoral arteries (SFA)), pulse wave velocity (PWV), bone mineral density (BMD) and left ventricular mass index (LVMI) over 12 months. FINDINGS: In the LC group, pre dialysis ionised calcium decreased -0.12 mmol/L (-0.18-0.06, P = 0.0001) and PTH increased 16 pmol/L (3.5-28.5, p = 0.01) from baseline to 12 months with no significant change in the HC group. In both groups, there was no progression of VC in AA or SFA and no change in PWV, LVMI or BMD. At 12 months, calcimimetics were prescribed in a higher percentage in the LC vs. HC groups (45.5% vs. 10.5%) with a lower proportion of the HC group being prescribed calcitriol (31.5% vs. 72%). DISCUSSION: Although dialysate calcium prescription influenced biochemical parameters it was not associated with difference in progression of VC between HC and LC groups. An important finding was the potential impact of alternate night NHD in attenuating progression of VC and inducing stabilisation of LVMI and PWV. PMID- 27364377 TI - Anabolic steroid use and body image psychopathology in men: Delineating between appearance- versus performance-driven motivations. AB - OBJECTIVE: Anabolic androgenic steroid (AAS) use has been robustly associated with negative body image, and eating- and muscularity-oriented psychopathology. However, with AAS being increasingly utilized for both appearance and athletic performance-related purposes, we investigated whether comorbid body image psychopathology varies as a function of motivation for usage. METHOD: Self reported motivation for current and initial AAS use was recorded amongst 122 AAS using males, alongside measures of current disordered eating and muscle dysmorphia psychopathology. RESULTS: Those reporting AAS for appearance purposes reported greater overall eating disorder psychopathology, F(2, 118)=7.45, p=0.001, etap(2)=0.11, and muscle dysmorphia psychopathology, F(2, 118)=7.22, p<0.001, etap(2)=0.11, than those using AAS primarily for performance purposes. Additionally, greater dietary restraint, F(2, 116)=3.61, p=0.030, etap(2)=0.06, functional impairment, F(2, 118)=3.26, p=0.042, etap(2)=0.05, and drive for size, F(2, 118)=10.76, p<0.001, etap(2)=0.15, was demonstrated in those using ASS for appearance purposes. DISCUSSION: Motivation for AAS use may be important in accounting for differential profiles of body image psychopathology amongst users. Men whose AAS use is driven primarily by appearance-related concerns may be a particularly dysfunctional subgroup. PMID- 27364376 TI - "Cre/loxP plus BAC": a strategy for direct cloning of large DNA fragment and its applications in Photorhabdus luminescens and Agrobacterium tumefaciens. AB - Heterologous expression has been proven to be a valid strategy for elucidating the natural products produced by gene clusters uncovered by genome sequencing projects. Efforts have been made to efficiently clone gene clusters directly from genomic DNA and several approaches have been developed. Here, we present an alternative strategy based on the site-specific recombinase system Cre/loxP for direct cloning gene clusters. A type three secretion system (T3SS) gene cluster (~32 kb) from Photorhabdus luminescens TT01 and DNA fragment (~78 kb) containing the siderophore biosynthetic gene cluster from Agrobacterium tumefaciens C58 have been successfully cloned into pBeloBAC11 with "Cre/loxP plus BAC" strategy. Based on the fact that Cre/loxP system has successfully used for genomic engineering in a wide range of organisms, we believe that this strategy could be widely used for direct cloning of large DNA fragment. PMID- 27364378 TI - Quantification of EtG in hair, EtG and EtS in urine and PEth species in capillary dried blood spots to assess the alcohol consumption in driver's licence regranting cases. AB - BACKGROUND: In Belgium, the analysis of indirect biomarkers such as carbohydrate deficient transferrin (CDT%), gamma-glutamyltransferase (GGT), aspartate aminotransferase/alanine aminotransferase (AST/ALT) and mean corpuscular volume (MCV), is currently used to monitor the alcohol consumption in cases of fitness to drive assessment. We evaluated the use of direct ethanol markers for this purpose, exclusively determined in matrices obtained via non- or minimally invasive sampling. METHODS: Three validated quantitative methods (ethylglucuronide (EtG) in hair and urine, ethylsulfate (EtS) in urine, and phosphatidylethanol species (PEth 16:0/18:1, PEth 18:1/18:1 and PEth 16:0/16:0) in capillary dried blood spots (C-DBS)) were used. Fifty volunteers, for whom fitness to drive had to be assessed and for whom a blood analysis for indirect biomarkers was requested, were included in the study. The sampling and analysis of hair, urine and C-DBS were added to the process currently used. RESULTS: Hair EtG (24/50) and C-DBS PEths (29/50) are more sensitive than the currently used indirect biomarkers (13/50 for CDT%) to detect excessive and chronic alcohol consumption and allow to disprove an abstinence period. Urinary EtG and EtS are useful parameters to determine recent alcohol consumption. CONCLUSION: The combined use of the three strategies allows better inference about the evolution of the alcohol consumption prior to the sampling. Moreover, the exclusive use of non- or minimally invasive sampling (hair, urine and C-DBS) allows this to be performed directly during the fitness to drive assessment by regular staff members. This approach offers the potential to improve the Belgian driver's licence regranting process. PMID- 27364379 TI - Interpreting habits in a new place: Migrants' descriptions of geophagia during pregnancy. AB - BACKGROUND AND INTRODUCTION: Previous studies of soil eating, or geophagia, among pregnant women in sub-Saharan Africa indicate the practice is widespread. Various explanations have been explored to explain the global phenomenon of soil eating, with the most compelling explanation focused on clay's ability to prevent or treat intestinal infection. The urban South African context for clay eating is not well understood. This paper explores clay consumption amongst pregnant migrants who are nationals of countries where clay consumption may be common. METHODS: I conducted in-depth interviews with a purposively selected group of Somali, Congolese, and Zimbabwean women (n = 23). Interviews included questions broadly related to maternal and infant nutrition. In addition, I conducted nine focus group discussions (n = 48) with adult Somali, Congolese (DRC), and Zimbabwean men (N = 3) and women (N = 6), segregated by country of origin and gender. This paper focuses specifically on responses related to geophagia. RESULTS: While Somali women did not report consuming clay or charcoal, Congolese and Zimbabwean participants self-reported commonly consuming clay during pregnancy, and at times also when not pregnant. Despite having heard public health messaging that discouraged the practice, participants largely did not describe this consumption in terms of health, but rather in terms of craving and habit. Participants described continued consumption of clay in South Africa, and the only reason for ceasing consumption was in cases of severe constipation. DISCUSSION: The widespread consumption of clay soil by Congolese and Zimbabwean women during pregnancy may be a mechanism through which identity was reasserted and reproduced in a foreign country. Participants' emphasis on clay consumption seemed related to the absence or expense of other craved foods, and perhaps also to feelings of loss in Cape Town. PMID- 27364380 TI - Cultural Orientation Trajectories and Substance Use: Findings From a Longitudinal Study of Mexican-Origin Youth. AB - Cultural adaptation may influence Latino youth substance use (SU) development, yet few longitudinal studies have examined cultural change over time and adolescent SU outcomes. Using longitudinal data collected annually across ages 10 16 from 674 Mexican-origin youth (50% female), the authors characterized cultural adaptation patterns for language use (English and Spanish use), values (American values and familism values), and identity (ethnic pride), and examined whether these cultural adaptation patterns were associated with differential SU risk. Youth with increasing bilingualism and high/stable family values had lower SU risk compared to youth who primarily spoke English and endorsed decreasing family values, respectively. Ethnic pride trajectories were not associated with SU. Findings highlight the importance of considering cultural change related to Latino youth SU. PMID- 27364381 TI - State of the art of biological processes for coal gasification wastewater treatment. AB - The treatment of coal gasification wastewater (CGW) poses a serious challenge on the sustainable development of the global coal industry. The CGW contains a broad spectrum of high-strength recalcitrant substances, including phenolic, monocyclic and polycyclic aromatic hydrocarbons, heterocyclic nitrogenous compounds and long chain aliphatic hydrocarbon. So far, biological treatment of CGW has been considered as an environment-friendly and cost-effective method compared to physiochemical approaches. Thus, this reviews aims to provide a comprehensive picture of state of the art of biological processes for treating CGW wastewater, while the possible biodegradation mechanisms of toxic and refractory organic substances were also elaborated together with microbial community involved. Discussion was further extended to advanced bioprocesses to tackle high concentration ammonia and possible options towards in-plant zero liquid discharge. PMID- 27364383 TI - Stiffness of uncured resin-composites assessed via cavity-packing forces. AB - OBJECTIVES: To evaluate the stiffness and packability of unset resin-composites at different temperatures, taking into account the cavity wall effect. MATERIALS AND METHODS: Six representative commercial resin-composites were selected. Each material was placed in mould of different sizes for example (phi=7, depth=5mm; or phi=3, depth=5mm) held at 26 or 37 degrees C. Maximum packing force (Fp) of the resin-composite was measured. A flat-ended stainless-steel probe with a diameter of either 6mm or 3mm was mechanically lowered onto and into the surface of each unset sample with a speed of 0.50mm/s to a depth of 2mm, which was held constant for 10s. The compressive force produced on the probe by the unset resin composites was plotted against time and the maximum value was identified (Fp). Peak stress Sp was calculated by dividing the Fp by area of the probe used. Data were analyzed by univariate ANOVA and multiple pair wise comparisons were performed using a Tukey post-hoc test to establish homogenous subsets (at p=0.05). RESULTS: Sp was taken as potential measure of stiffness. It ranged from 0.12 to 4.21MPa and from 0.07 to 3.08MPa at 26 and 37 degrees C, respectively. Univariate ANOVA showed significant influence of the plunger cavity ratios, temperature and materials on Sp (p<0.001). A strong interaction was also found between plunger cavity ratios, temperature and materials for Sp (p<0.05). CONCLUSION: Peak stress Sp is a useful parameter for characterizing the stiffness of uncured resin-composite materials, additionally resin-composite formulation, temperature and wall effect did effect the packability of resin-composite. PMID- 27364384 TI - Scaling-up innovation as a means of tackling health inequalities. Commentary. AB - ISSUE: The introduction of inclusive healthcare innovations as a means of improving the welfare of marginalized groups is now being witnessed in developing countries as a crucial process of modernization and industrialization. In this respect, there has been much discussion regarding the most effective strategies of scaling up innovative healthcare interventions in these parts of the world. EVIDENCE: The topics of discussion have included accessibility and cost effectiveness; sustainability; infrastructure to support implementation; political will; advocacy; strong leadership; tailoring the scaled-up approach to the local context; and various potential models of funding. IMPLICATIONS: Given that policy advocacy plays a critical role in creating a favourable environment for inclusive healthcare innovations, intensive lobbying will be necessary as a means to achieve effective scaling-up in addition to tackling the respective development challenges more efficiently. With this in mind, funders will need to mobilize substantial investment for innovations that respond to the most pressing global public health issues. PMID- 27364382 TI - Rv2074 is a novel F420 H2 -dependent biliverdin reductase in Mycobacterium tuberculosis. AB - Bilirubin is a potent antioxidant that is produced from the reduction of the heme degradation product biliverdin. In mammalian cells and Cyanobacteria, NADH/NADPH dependent biliverdin reductases (BVRs) of the Rossmann-fold have been shown to catalyze this reaction. Here, we describe the characterization of Rv2074 from Mycobacterium tuberculosis, which belongs to a structurally and mechanistically distinct family of F420 H2 -dependent BVRs (F-BVRs) that are exclusively found in Actinobacteria. We have solved the crystal structure of Rv2074 bound to its cofactor, F420 , and used this alongside molecular dynamics simulations, site directed mutagenesis and NMR spectroscopy to elucidate its catalytic mechanism. The production of bilirubin by Rv2074 could exploit the anti-oxidative properties of bilirubin and contribute to the range of immuno-evasive mechanisms that have evolved in M. tuberculosis to allow persistent infection. PMID- 27364385 TI - A sex and gender perspective in medicine: a new mandatory challenge for human health. Preface. PMID- 27364386 TI - Why the study of the effects of biological sex is important. Commentary. AB - Biological sex significantly affects the presentation, outcome of treatment and progression of disease. However, the role of sex has yet underestimated consequences for physiology and pathology. We put forward that a better understanding of the effects of sex in pathophysiology and the underlying mechanisms is necessary. This may facilitate the identification of targets that respond to specific therapies, thereby contributing towards a more appropriate and individualised medical care for both men and women. PMID- 27364387 TI - Health status of the Italian people: gender inequalities. Commentary. AB - Differences between male and female affect diseases onset, evolution and prognosis. In terms of survival, women have a higher life expectancy at birth than men, with strong differences at regional level (the highest values in Trento AP and the lowest in Campania). Smoking, alcohol consumption, overweight and obesity and physical activities indicators are analyzed among men and woman. A reduction in smokers and number of smoked cigarettes is observed, especially among men. Men also show a higher number of ex-smokers than woman. Also for alcohol consumption, the prevalence of consumers at risk is higher among men than women. Overweight and obesity are more prevalent among men than women, the same as physical activity played continuously and occasionally. Gender differences are also shown in hospitalization rate and mortality rate for ischemic heart disease, affecting men twice more than women. The analysis shows a good health status condition of Italian people, but it is important to be aware that gender is one of essential characteristics in health care field, independently of people age. PMID- 27364388 TI - Sex And Gender Equity in Research (SAGER): reporting guidelines as a framework of innovation for an equitable approach to gender medicine. Commentary. AB - Sex and gender are important determinants of health and influence research findings in a variety of ways, yet they are often overlooked and underreported. This oversight limits the generalizability of research findings and their applicability to clinical practice. The objective of this paper is to point out how journal editors can influence better reporting of sex and gender in research by establishing a methodological framework directly addressing authors of scientific publications, as well as referees, and indirectly affecting all the stakeholders in the research cycle, from funders to policy-makers and citizens. Such a framework is represented by the Sex And Gender Equity in Research (SAGER) guidelines, developed by the European Association of Science Editors (EASE) to encourage a more systematic approach to the reporting of sex and gender in research across disciplines. The paper includes the rationale and basic principles of the SAGER guidelines. PMID- 27364389 TI - Gender-related differences in lifestyle may affect health status. AB - Consistent epidemiological and clinical evidence strongly indicates that chronic non-communicable diseases are largely associated with four lifestyle risk factors: inadequate diet, physical inactivity, tobacco use, and excessive alcohol use. Notably, obesity, a worldwide-growing pathological condition determined by the combination between inadequate diet and insufficient physical activity, is now considered a main risk factor for most chronic diseases. Dietary habits and physical activity are strongly influenced by gender attitudes and behaviors that promote different patterns of healthy or unhealthy lifestyles among women and men. Furthermore, different roles and unequal relations between genders strongly interact with differences in social and economic aspects as well as cultural and societal environment. Because of the complex network of factors involved in determining the risk for chronic diseases, it has been promoting a systemic approach that, by integrating sex and gender analysis, explores how sex-specific biological factors and gender-related social factors can interact to influence the health status. PMID- 27364390 TI - Sex-driven vulnerability in stress and drug abuse. AB - A growing body of literature shows that a link exists between substance abuse and stress and that the crosstalk of sex hormones with the neuroendocrine system might differently prime vulnerability to drug addiction in male and female subjects. Thus, understanding the neurobiological mechanisms of addiction and the identification of sex-driven determinants in vulnerability to drug abuse may help to better devise and/or implement strategic (pharmacological, behavioural, social) interventions to prevent or face the issue of addiction. Differences between sexes can be found at all stages of life (in both the animal model and human studies) and may account for genetic, epigenetic and environmental/hormonal factors that in turn affect the functionality of the whole organism leading also to a sex-driven differential vulnerability or resilience to non-communicable pathologies. These include the onset and precipitation of stress-related psychiatric disorders as well as "substance-related and addictive disorders" (as defined in the DSM-V). This paper reviews the scientific literature highlighting significant differences in male and female subjects in stress and neuroendocrine function and the implications for sex-dependent differential vulnerability to drug addiction. PMID- 27364391 TI - Gender disparity in addiction: an Italian epidemiological sketch. AB - INTRODUCTION: Gender disparity in different fields of addiction such as tobacco smoking, alcohol use, drugs of abuse consumption and doping practice has been investigated in Italian population. METHODS: We used the surveys and studies carried out for the above reported issues in recent years as revised by the "National Observatory on Tobacco smoke, Drugs of abuse, Alcohol and Doping" at Istituto Superiore di Sanita. RESULTS: Concerning tobacco habit, the trend of smoking women has been in constant decrease from a 19.7% in 2010 to a 16.9% in 2015, differently from men who passed from a 23.9% in 2010 to a 25.1% in 2015 with a slight increase in the habit. With respect to alcohol, in the last five years an increasing trend of consumption has been observed in 18-24 years old women, with 53% drinking women in the age range of 18-19 years overcoming the 50.4% general female population. Generally speaking, a one to four ratio can be underlined in the percentage of elderly women with a risky alcohol consumption with respect to men, while in case of adolescents and young adults gender disparity is not so pronounced. Drug abuse still remains a prevalent male phenomenon. However, an increase in cannabis users for both genders has been reported with a prevalence of "once in the life" around 20%, although more pronounced in females (+2.66 percentage points for females vs +0.93 percentage points in male). With respect to cocaine, the second most consumed drug, a reduction in consumption has been recently observed mainly in female population ( 42.1%) than in men one (-27.5%). Finally, there are significant gender differences in doping attitude and/or in doping profiling. First of all, males seem to be more exposed to doping than females The prohibited substances most frequently used by females athletes are "Diuretics and Masking Agents" (38.3% positive female vs 14% males) compared to males athletes who use mostly anabolic agents (20.1% males vs 11.2% females). CONCLUSIONS: Results presented for the different fields of addiction show that a gender disparity is apparent and that females are less prone in having an addiction behaviour, although the young generation seems to increase that tendency. PMID- 27364393 TI - Gender issues on occupational safety and health. AB - The increasing proportion of women in the workforce raises a range of gender related questions about the different effects of work-related risks on men and women. Few studies have characterized gender differences across occupations and industries, although at this time, the gender sensitive approach is starting to acquire relevance in the field of human preventive medicine. The European Agency for Safety and Health at Work has encouraged a policy of gender equality in all European member states. Italy has adopted European provisions with new specific legislation that integrates the previous laws and introduces the gender differences into the workplace. Despite the fact that gender equal legislation opportunities have been enacted in Italy, their application is delayed by some difficulties. This review examines some of these critical aspects. PMID- 27364392 TI - Gender differences in pain and its relief. AB - There is much evidence to suggest that gender is an important factor in the modulation of pain. Literature data strongly suggest that men and women differ in their responses to pain: they are more variable in women than men, with increased pain sensitivity and many more painful diseases commonly reported among women. Gender differences in pharmacological therapy and non-pharmacological pain interventions have also been reported, but these effects appear to depend on the treatment type and characteristics. It is becoming very evident that gender differences in pain and its relief arise from an interaction of genetic, anatomical, physiological, neuronal, hormonal, psychological and social factors which modulate pain differently in the sexes. Experimental data indicate that both a different modulation of the endogenous opioid system and sex hormones are factors influencing pain sensitivity in males and females. This brief review will examine the literature on sex differences in experimental and clinical pain, focusing on several biological mechanisms implicated in the observed gender related differences. PMID- 27364394 TI - The influence of sex and gender on immunity, infection and vaccination. AB - Sex/gender significantly contribute to shape the immune responses, contributing to differences in the pathogenesis of infectious diseases in males and females, the response to viral vaccines and the prevalence of autoimmune diseases. Females typically develop higher innate, humoral and cellular immune responses to viral infections and in response to vaccine. At the same time, women are more prone to autoimmune diseases and experience more adverse reactions to vaccination. Hormonal, genetic and environmental factors between males and females may affect the immune responses and the sex-related outcome of vaccination. Knowledge of the mechanisms involved in sex disparity in immune responses will contribute to identify the ways to reduce adverse reactions in females and to improve the immune responses in males. This is necessary to adequately protect both sexes against the immune-mediated and infectious diseases with the long-term goal of personalizing the therapies for males and females. PMID- 27364395 TI - Sex-based differences in autoimmune diseases. AB - Autoimmune diseases are characterized by an exaggerated immune response leading to damage and dysfunction of specific or multiple organs and tissues. Most autoimmune diseases are more prevalent in women than in men. Symptom severity, disease course, response to therapy and overall survival may also differ between males and females with autoimmune diseases. Sex hormones have a crucial role in this sex bias, with estrogens being potent stimulators of autoimmunity and androgens playing a protective role. Accumulating evidence indicates that genetic, epigenetic and environmental factors may also contribute to sex-related differences in risk and clinical course of autoimmune diseases. In this review, we discuss possible mechanisms for sex specific differences in autoimmunity with a special focus on three paradigmatic diseases: systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. PMID- 27364396 TI - The gender perspective in cancer research and therapy: novel insights and on going hypotheses. AB - Cancer represents a leading cause of death whose incidence is steadily increasing worldwide due to the population aging. The Global Health Observatory of the World Health Organization reported that approximately 13% of all deaths are caused by cancer. In the 2012 the estimated total number of cancer deaths was 1.75 million, 56% in men and 44% in women. Gender is recognized to play a role in cancer incidence, progression and response to therapy. Besides anatomical and hormonal disparities, genetic differences should be considered when assessing the effects of gender on cancer. Accumulating evidence also support the existence of sex driven differences in immune responses. Until today clinical trials and research in animal models have been gender unbalanced. In consideration of the differences between sexes observed in cancer, sex should represent an important stratification factor to be included in all randomized clinical trials for a better understanding of biological differences between men and women, which may yield improved targeted therapies. PMID- 27364397 TI - Gender differences in cardiac hypertrophic remodeling. AB - Cardiac remodeling is a complex process that occurs in response to different types of cardiac injury such as ischemia and hypertension, and that involves cardiomyocytes, fibroblasts, vascular smooth muscle cells, vascular endothelial cells, and inflammatory cells. The end result is cardiomyocyte hypertrophy, fibrosis, inflammation, vascular, and electrophysiological remodeling. This paper reviews a large number of studies on the influence of gender on pathological cardiac remodeling and shows how sex differences result in different clinical outcomes and therapeutic responses, with males which generally develop greater cardiac remodeling responses than females. Although estrogens appear to have an important role in attenuating adverse cardiac remodeling, the mechanisms through which gender modulates myocardial remodeling remain to be identified. PMID- 27364398 TI - Sex-related biomarkers in cardiovascular and neurodegenerative disorders. AB - Despite considerable advances in the treatment of human inflammatory diseases, such as cardiovascular and neurological disorders, they remain the leading cause of death in developed countries. From a clinical perspective, an active area of investigation focuses on the identification of diagnostic and prognostic biomarkers, because preventing events in those at risk of chronic inflammatory disease is likely to have a substantial impact on the overall public-health burden. The sex difference has not been considered previously as important in the evaluation of biomarkers of human diseases, notwithstanding it is now ascertained that the severity of these disorders is correlated with sex hormones which modulate the inflammatory response. The aim of the present brief review is to report and comment the state of art regarding the sex-related biomarkers in cardiovascular and neurodegenerative disorders, focusing on those compounds showing potential prognostic- and diagnostic values, and/or acting as indicators of the therapeutic treatment efficacy. PMID- 27364399 TI - Mild cognitive impairment, from theory to practical intervention: "Camminando e leggendo... ricordo" (Walking and reading... I remember), an action plan. The Treviso Dementia (TREDEM) Registry. AB - Dementia is one of the most disabling health conditions in older people. Increasing attention is paid to the preclinical phase of dementia and to the prevention programs to reduce the number of patients in the future. Aims of the current study are: a) to present Mild Cognitive Impairment (MCI) as a heterogeneous risk factor and to expose the relationship between cognitive impairment and lifestyles such as physical activity, Mediterranean diet, reading and socialization; b) to present a model, called "Camminando e leggendo... ricordo" (CLR), as a practical experience of secondary prevention aimed at MCI older people. The CLR model is composed of a program of physical and reading activities in group to promote healthy lifestyles. Here we present a protocol to evaluate the effectiveness of our intervention model. A multidimensional geriatric assessment will be carried out. A questionnaire for the detection of frailty, disability and for the adherence to the Mediterranean diet will be administered. The Psychological General Well-Being Index (PGWBI) will be used to assess the quality of life. CLR is an intervention model for secondary prevention in MCI subjects. It is the description of a practical proposal aimed at improving lifestyles and reducing the risk of dementia. PMID- 27364400 TI - Validation of the Italian version of the Apathy Evaluation Scale (AES-I) in institutionalized geriatric patients. AB - OBJECTIVES: Apathy is a very common symptom in the institutionalized elderly and represents a condition of both clinical and public health importance. The Apathy Evaluation Scale (AES) has been shown to be a valid and reliable tool for characterizing, quantifying and differentiating apathy in various health conditions. The aims of this study were to establish the validity and reliability of the Italian version of the AES, and to assess the severity of apathy in a sample of Italian institutionalized geriatric patients. METHOD: Data were collected from clinical interviews using the AES informant version (AES-I). Associations between measures of apathy and depression, cognitive functioning and perceived quality of life were evaluated, as well as the effects of the living environment on apathetic symptoms. RESULTS: Multiple forms of reliability and validity (i.e. test-retest, internal consistency, discriminability of apathy rating from a standard measure of depression) were satisfied. Our results also show that the characteristics of the care setting may affect the severity of apathetic symptoms. CONCLUSIONS: The AES-I Italian version is a reliable and valid instrument for measuring apathy in Italian patients, also allowing a direct comparison with data gathered in other countries. PMID- 27364401 TI - A computational tool for evaluating HIFU safety. AB - BACKGROUND: High Intensity Focused Ultrasound (HIFU) is a noninvasive treatment for therapeutic applications, in particular the treatment of either benign or malignant tumor lesions. HIFU treatment is based on the power of a focused ultrasound beam to locally heat biological tissues over a necrotic level with minimal impact on the surrounding tissues. Therapies based on HIFU are becoming widely spread in the panorama of options offered by the Health Care System. Consequently, there is an ever increasing need to standardise quality assurance protocols and to develop computational tools to evaluate the output of clinical HIFU devices and ensuring safe delivery of HIFU treatment. AIMS: Goal of this study is the development of a computational tool for HIFU ablation therapy to assure safety of the patient and effectiveness of the treatment. RESULTS: The simulated results provide information about the behaviour of the focalized ultrasound in their interaction with different biological tissues. CONCLUSIONS: Numerical simulation represents a useful approach to predict the heath deposition and, consequently, to assess the safety and effectiveness of HIFU devices. PMID- 27364402 TI - Break with tradition: donating cadavers for scientific purposes and reducing the use of sentient beings. AB - In recent years, the development of research and the increased awareness of our moral duties beyond the human species have pushed the scientific community to revise widely-accepted ontological reductionist views that regard non-human animals as mere things. The new horizons offered by the development of advanced research methods therefore require an on-going commitment to new perspectives able to find the right balance between the need for scientific knowledge on one hand and the respect for animal life on the other. This is in line with increasing attention to animal welfare and expansion of the "3Rs model": replacement, reduction, refinement.With the view of promoting the adoption of alternative methods, human body donation for research can contribute not only to the acquisition of important information for human health and for doctors' training, but also can reduce significantly the number of animals sacrificed.By investigating the scientific and ethical reasons that may encourage cadaver donation, the authors aim to promote the adoption of the practice in Italy following other European experiences. PMID- 27364403 TI - Black flies (Diptera, Simuliidae) as ecological indicators of stream ecosystem health in an urbanizing area (Rome, Italy). AB - INTRODUCTION: The effectiveness of Simuliidae (Diptera, Nematocera) as indicators of stream health was tested in the urbanizing area of Rome, Central Italy. METHODS: 108 sampling sites were investigated in the spring to acquire data on environmental variables and black fly species. RESULTS AND DISCUSSION: The comparison of sampling and literature data highlighted the disappearance of some species (Simulium reptans, S. vernum, S. liriense), possibly due to water pollution and land use changes. Correspondence analysis confirms altitude as the main factor influencing black fly species' distribution. However, water quality becomes predominant when considering exclusively plain sites: "ornatum" and "equinum" species groups show the greatest tolerance to chemical pollution. The high course of the Aniene river and its tributaries were sampled bimonthly, confirming the spatial-temporal black fly successions previously observed in central Apennines. The results also indicate that S. ornatum may supplant all other species in areas where the rural use is substituted by urban landscape. CONCLUSION: In conclusion, black flies can be considered good environmental indicators to assess ecological health of both watercourses and surrounding landscapes. PMID- 27364404 TI - Prevalence of Salmonella strains in wild animals from a highly populated area of north-eastern Italy. AB - INTRODUCTION: Salmonella is a ubiquitous pathogen that can infect host species, like wild birds, rodents, and/or arthropods, which may transmit infection to domestic animals and human population. AIM: In order to assess the related risk, a cross-sectional study was performed on 1114 carcasses of wild animals from a north-eastern area of the Emilia-Romagna Region, Italy. MATERIALS AND METHODS: During post mortem examination, intestine samples were cultured. A statistical analysis demonstrated that there is no correlation between the presence of sub clinically infected animals and greater human population density. In contrast, a significant correlation between the number of carcasses positive for Salmonella spp. and greater spatial density of pig, poultry, and cattle farms was observed (p < 0.01). RESULTS: The results of the present study show that wild animals with omnivorous feeding habits are particularly exposed to Salmonella colonization and, consequently, to spreading the organism. Regarding drug resistance, this study confirms the resistance to antimicrobials is increasing in commensal and environmental isolates. PMID- 27364405 TI - "Wind of change": the role of human centered healthcare factors in the implementation of clinical governance in an Italian University teaching hospital. AB - BACKGROUND: Clinical governance (CG) is an approach to quality improvement in healthcare aimed at achieving a patient-centered health care system. The main objective of this study was to highlight human centered healthcare latent factors underlying the results of a CG assessment performed in the teaching hospital "A. Gemelli" of Rome, Italy. MATERIALS AND METHODS: CG implementation levels were assessed through OPTIGOV(c) (OPTimizing healthcare GOVernance), a CG scorecard methodology. In order to identify the variables generating latent factors that can influence the governance of the Hospital, the multiple correspondence analysis (MCA) was applied. RESULTS: The application of OPTIGOV(c) showed a good CG implementation level in the Gemelli Hospital. By applying MCA, the variables aggregated so as to define 3 latent factors (F1: assessment for people oriented improvement strategy; F2: assessment for people targeted management; F3: tracking for timely accountable people) explaining as a whole 82.68% of the total variance and respectively 48.09% (F1), 24.95% (F2) and 9.64% (F3). CONCLUSIONS: The heuristic interpretation of the three latent factors could bring back to the concept of humanization in healthcare. This study shows that in the teaching hospital "A. Gemelli" humanization in healthcare is the driver of health care quality improvement. PMID- 27364406 TI - Information needs of young Italians accessing the AIDS/STI Helpline at the Italian National Institute of Health. AB - INTRODUCTION: HIV/AIDS and sexually transmitted infections (STI) have a relevant impact on health and sexual behavior of adolescents and young adults (range of age between 13 and 19 years). The AIDS and sexual transmitted infections (STI) Helpline of the Italian Istituto Superiore di Sanita (National Institute of Health), and also funded by the Italian Ministry of Health, has been active since 1987 providing personalized counselling interventions on HIV/AIDS and STI. AIM AND METHODS: The present study gathered data and questions issues from calls at AIDS/STI Helpline in the period 1987-2014, with the specific aim of assessing the level of awareness and information needs on HIV/AIDS and STI among people aged under 25 years, in relation to potential risky behavior. RESULTS: Data show that young subjects who called the helpline in the period considered are about the 26% of the total users, with a decreasing trend over the years. The 28% of young users reported a "risky behavior" for STI, with a chance statistically higher in the age range 15-19 years and in the MSM (men who have sex with men)/bisexuals users, which tended to decrease in the last years. Of note, a marked increase of the amount of young users not displaying behaviors at risk for HIV or STI has been observed in the years. PMID- 27364407 TI - Efficacy and safety of spinning exercise in middle-aged and older adults with metabolic syndrome: randomized control trial. AB - BACKGROUND: Few studies have been conducted to investigate the effects of spinning exercise on cardio-vascular weal. AIM: To assess whether a 6 months spinning training, combined with proper diet, is more effective than standard training programs and diet alone in improving metabolic abnormalities in middle aged and older adults. DESIGN: Randomized clinical trial. SETTING: Rehabilitation Unit of our Department. POPULATION: Patients with Metabolic Syndrome (MetS) according to the National Cholesterol Education Program Adult Treatment Panel III diagnostic criteria. METHODS: Patients were randomly assigned to receive treatment with diet (group A, n = 10), with diet and general gymnastics program (group B, n = 10), with diet and spinning physical training program (group C, n = 10). RESULTS: During the study period we observed a significant reduction in blood pressure (group C: systolic blood pressure p = 0.03; diastolic blood pressure p = 0.004 / group B: systolic blood pressure p = 0.001), in lipid profile (group B: plasma total cholesterol p = 0.001; triglycerides p = 0.001 / group C: plasma total cholesterol p = 0.04); in fasting blood glucose (group B: p = 0.01; group C: p = 0.008); in Homeostatic Model Assessment of Insulin Resistance (group B: p = 0.01; group C: p = 0.001); in waist circumference (group C: p = 0.005; group A: p = 0.02; group B: p = 0.04). No patients reported adverse events during follow-up. CONCLUSION: Our results confirm the effectiveness of spinning training combined with diet in the management of MetS. CLINICAL REHABILITATION IMPACT: The findings provide a preliminary evidence to support that spinning training may represent a useful and safe intervention also in middle-aged and older adults geriatric with multiple CV risk factors. PMID- 27364408 TI - A new treatment in the rehabilitation of the paretic upper limb after stroke: the ARAMIS prototype and treatment protocol. AB - BACKGROUND: In recent years, as part of the rehabilitation of post stroke patients, the use of robotic technologies to improve recovery of upper limb has become more widespread. The Automatic Recovery Arm Motility Integrated System (ARAMIS) is a concept robot and prototype designed to promote the functional interaction of the arms in the neurorehabilitation of the paretic upper limb. Two computer-controlled, symmetric and interacting exoskeletons compensate for the inadequate strength and accuracy of the paretic arm and the effect of gravity during rehabilitation. Rehabilitation is possible in 3 different modalities; asynchronous, synchronous and active-assisted. OBJECTIVES: To compare the effectiveness of robotic rehabilitation by an exoskeleton prototype system with traditional rehabilitation in motor and functional recovery of the upper limb after stroke. METHODS: Case-control study, 52 patients enrolled in the study, 28 cases (women: 8, age: 65 +/- 10 yrs) treated with ARAMIS and 24 controls (women: 11, age: 69 +/- 7 yrs) with conventional rehabilitation. Motor impairment assessed before and after treatment with Fugl-Meyer scale and Motricity Index, level of disability assessed with the Functional Independence Measure. A questionnaire was also administered to assess the patient's tolerance to robotic therapy. RESULTS: After 28 +/- 4 sessions over a 54 +/- 3.6-day period, the patients treated by ARAMIS had an improvement on the Fugl-Meyer scale (global score from 43 +/- 18 to 73 +/- 29; p < 0.00001), Motricity Index scale (p < 0.004) and Functional Independence Measure (p < 0.001). A lesser degree of improvement was achieved using conventional rehabilitation, the Fugl-Meyer global score of the control group improved from 41 +/- 13 to 58 +/- 16 (p < 0.006) and the motor function item from 9.4 +/- 4.1 to 14.9 +/- 5.8 (p < 0.023). CONCLUSIONS: Motor improvement was greater at the wrist and hand than at shoulder and elbow level in patients treated by ARAMIS and controls, but it was significantly greater in ARAMIS-treated patients than in controls. The results indicate a greater efficacy of ARAMIS compared to conventional rehabilitation. PMID- 27364409 TI - sodC genes expression in Escherichia coli O157:H7 strains. AB - INTRODUCTION: E. coli O157:H7 has three sodC genes encoding for Cu,Zn superoxide dismutase. We evaluated the expression of chromosomal sodC in distinct phases of growth in different strains, and we examined the mutual capability of chromosomal and prophagic genes to influence their expression. METHODS: We used One Step real time RT-PCR technology to study the expression of sodC genes in several E. coli strains. RESULTS: In three of four analysed E. coli O157:H7 strains the chromosomal sodC gene was more expressed in exponential phase than in stationary phase, unlike it occurs in the E. coli K12 strain. The expression of the chromosomal gene was always higher than that of the prophagic copies. Deletion of prophagic or chromosomal sodC genes had no effect on the expression of the residual gene. CONCLUSION: Our study highlights an inherent variability in number and level of expression of sodC genes in E. coli O157:H7 strain. PMID- 27364410 TI - Virus reactivations after autologous hematopoietic stem cell transplantation detected by multiplex PCR assay. AB - Several studies have indicated that viral reactivations following allogeneic hematopoietic stem cell transplantation (allo-HSCT) are frequent, but viral reactivations after autologous HSCT (auto-HSCT) have not been investigated in detail. We performed multiplex polymerase chain reaction (PCR) assay to examine multiple viral reactivations simultaneously in 24 patients undergoing auto-HSCT between September 2010 and December 2012. Weekly whole blood samples were collected from pre- to 42 days post-HSCT, and tested for the following 13 viruses; herpes simplex virus 1 (HSV-1), HSV-2, varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), HHV 7, HHV-8, adeno virus (ADV), BK virus (BKV), JC virus (JCV), parvovirus B19 (B19V), and hepatitis B virus (HBV). Fifteen (63%) patients had at least one type of viral reactivation. HHV6 (n = 10; 41.7%) was most frequently detected followed by EBV (n = 7; 29.2%). HHV-6 peaked on day 21 after HSCT and promptly declined. In addition, HBV, CMV, HHV7, and B19V were each detected in one patient. HHV6 reactivation was detected in almost half the auto-HSCT patients, which was similar to the incidence in allo-HSCT patients. The incidence of EBV was unexpectedly high. Viral infections in patients undergoing auto-HSCT were higher than previously reported in other studies. Although there were no particular complications of viral infection, we should pay attention to possible viral reactivations in auto-HSCT patients. J. Med. Virol. 89:358-362, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27364411 TI - Aging and frailty or frailty and aging? PMID- 27364412 TI - Comorbidities in elderly patients with pulmonary disease. PMID- 27364413 TI - Thrombolysis in older adults: To do or not to do, this is the question! PMID- 27364414 TI - A rare cause of chronic diarrhoea in an elderly patient. PMID- 27364415 TI - "Oldest old" man with odynophagia and generalized asthenia: It could be tetanus! PMID- 27364416 TI - Do Serum Creatinine Levels Show Clinically Significant Fluctuations on Serial Determinations on the Siemens Advia 1800 Analyzer? AB - BACKGROUND: The goal of this work was to determine whether there are clinically significant fluctuations in the level of serum creatinine on serial determinations, especially in the borderline range (1.1-1.3 mg/dl), after specimen storage. METHODS: Sixty-one serum samples were analyzed. They were divided into three categories based on the initial serum creatinine measurement: low (<=1.0 mg/dl), borderline (1.1-1.3 mg/dl), and high (>=1.4 mg/dl). The specimens were stored at 4 degrees C and run on the Siemens Advia 1800 chemistry analyzer on days 1, 3, and 11. RESULTS: Statistical comparisons of the three groups were made using the unpaired t-test, yielding a two-tailed P-value for each group comparison. The P-values ranged from 0.0829 to 0.3892, indicating no statistically significant difference between the standard deviations of each group. CONCLUSIONS: Mild-to-moderate fluctuations in precision occur in successive serum creatinine determinations. The overwhelming majority of these fluctuations should not affect clinical decision making. PMID- 27364417 TI - Learning whilst on-call: a vital part of radiology training? PMID- 27364418 TI - Remembering a Pioneer of Psychiatric Mental Health Nursing. PMID- 27364419 TI - Racial disparities in birth care: Exploring the perceived role of African American women providing midwifery care and birth support in the United States. AB - BACKGROUND: Midwifery care has been linked to positive birth outcomes. Despite the broad racial disparities in maternal and infant outcomes in the United States (US), little is known about the role of minority women in either providing or receiving this type of care. A vibrant community of minority women, who self identify as providing these services, exists online. In this exploratory study we ask how they describe their role; view their practice; and position themselves in the broader discussions of racial health disparities in the US. METHODS: Using an internet mediated qualitative design we analyse online narratives from self described African-American nurse-midwives, lay midwives and birth assistants; we found 28 unique websites. We collected and analysed narrative material from each site. We used a thematic analysis approach to identify recurrent and emergent themes in relation to the study question. RESULTS: Narratives identified a strong link to the past, as providers viewed their practice in a historical perspective linking African roots, to the diaspora, and to current African-American struggles. Providers engaged both in direct clinical work, and in activist roles. Advocacy efforts sought to expand numbers of minority birth care workers and to extend the benefits of woman-centred birth care to underserved communities. CONCLUSION: Results demonstrate the continued existence and important role of diverse types of African-American birth care providers in minority communities in the US. Recognition, support, and increasing the number of midwives of colour is important in tackling racial inequalities in health. Further research should explore minority access to woman-centred care. PMID- 27364422 TI - Minimally invasive transforaminal lumbar interbody fusion with percutaneous navigated guidewireless lumbosacral pedicle screw fixation. AB - This video details the minimally invasive approach for treatment of a symptomatic Grade II lytic spondylolisthesis with high-grade foraminal stenosis. In this procedure, the use of a navigated, guidewireless technique for percutaneous pedicle screw placement at the lumbosacral junction is highlighted following initial decompression and transforaminal interbody fusion. Key steps of the procedure are delineated that include positioning, exposure, technique for interbody fusion, intraoperative image acquisition, and use of a concise 2-step process for navigated screw placement without using guidewires. The video can be found here: https://youtu.be/2u6H4Pc_8To . PMID- 27364420 TI - Ellagic acid confers protection against gentamicin-induced oxidative damage, mitochondrial dysfunction and apoptosis-related nephrotoxicity. AB - OBJECTIVES: The aim of this study was to investigate the possible protective effect of ellagic acid (EA) against gentamicin (GEN)-induced nephrotoxicity using biochemical, molecular and histopathological approaches. METHODS: Rats (n = 24) were divided into four groups: control, GEN (100 mg/kg, i.p.), EA (10 mg/kg, p.o.) and GEN plus EA. The regimes were administered for 10 successive days. 24 h after last treatment, kidney and blood samples were collected. KEY FINDINGS: Ellagic acid treatment significantly reduced plasma creatinine and urea levels, which were initially increased due to GEN administration. Also, EA significantly ameliorated oxidative stress markers including lipid peroxidation, catalase (CAT) and superoxide dismutase (SOD) enzyme activity as well as glutathione (GSH) content in kidney tissue. Activation of caspase-3 and increase in the ratio of Bcl-2/Bax expression observed in GEN-treated group were significantly ameliorated by EA treatment. EA also protected GEN-induced mitochondrial damages as indicated by decreasing the mitochondrial ROS content, preventing of mitochondrial membrane potential (MMP) loss, reducing mitochondrial swelling and decreasing cytochrome c release. In addition, histopathological findings revealed that EA ameliorates GEN induced kidney injury. CONCLUSIONS: Our findings suggest that EA treatment attenuates GEN-induced nephrotoxicity, which may be ascribed to its antioxidant and anti-apoptotic properties. PMID- 27364421 TI - Development of quantitative radioactive methodologies on paper to determine important lateral-flow immunoassay parameters. AB - The lateral-flow immunoassay (LFA) is a well-established diagnostic technology that has recently seen significant advancements due in part to the rapidly expanding fields of paper diagnostics and paper-fluidics. As LFA-based diagnostics become more complex, it becomes increasingly important to quantitatively determine important parameters during the design and evaluation process. However, current experimental methods for determining these parameters have certain limitations when applied to LFA systems. In this work, we describe our novel methods of combining paper and radioactive measurements to determine nanoprobe molarity, the number of antibodies per nanoprobe, and the forward and reverse rate constants for nanoprobe binding to immobilized target on the LFA test line. Using a model LFA system that detects for the presence of the protein transferrin (Tf), we demonstrate the application of our methods, which involve quantitative experimentation and mathematical modeling. We also compare the results of our rate constant experiments with traditional experiments to demonstrate how our methods more appropriately capture the influence of the LFA environment on the binding interaction. Our novel experimental approaches can therefore more efficiently guide the research process for LFA design, leading to more rapid advancement of the field of paper-based diagnostics. PMID- 27364423 TI - Biplanar x-ray fluoroscopy for sacroiliac joint fusion. AB - Chronic pain originating from the sacroiliac joint (SI) can cause severe dysfunction. Although many patients respond to conservative management with NSAIDs, some do need further treatment in the form of SI joint fusion (SIJF). To achieve safe and successful SIJF, intraoperative x-ray fluoroscopy is mandatory to avoid serious damages to nearby vascular and neural structures. Each step of the procedure has to be confirmed by anteroposterior (AP) and lateral projections. With a single-arm x-ray, the arch has to be moved back and forth for the AP and lateral projections, and this lengthens the procedure. To achieve the same results in less time, the authors introduced simultaneous biplanar fluoroscopy with 2 x-ray arches. After the patient is positioned prone with the legs spread apart in the so-called Da Vinci position, one x-ray arch for the lateral projection is placed at a right angle to the patient, and a second x-ray machine is placed with its arch between the legs of the patient. This allows simultaneous AP and lateral x-ray projections and, in the authors' hands, markedly speeds up the procedure. Biplanar fluoroscopy allows excellent AP and lateral projections to be made quickly at any time during the surgical procedure. This is particularly useful in cases of bilateral SI joint fusion if both sides are done at the same time. The video can be found here: https://youtu.be/TX5gz8c765M . PMID- 27364424 TI - Mini-open anterior lumbar interbody fusion. AB - In deformity surgery, anterior lumbar interbody fusion provides excellent biomechanical support, creates a broad surface area for arthrodesis, and induces lordosis in the lower lumbar spine. Preoperative MRI, plain radiographs, and, when available, CT scan should be carefully assessed for sacral slope as it relates to pubic symphysis, position of the great vessels (especially at L4/5), disc space height, or contraindication to an anterior approach. This video demonstrates the steps in an anterior surgical procedure with minimal open exposure. The video can be found here: https://youtu.be/r3bC4_vu1hQ . PMID- 27364425 TI - Introduction to Lumbosacral and Sacropelvic Fixation Strategies. AB - We are pleased to present this Neurosurgical Focus video supplement on lumbosacral and sacropelvic fixation strategies. Despite advancement in surgical techniques and technologies in spine, achieving consistent solid fusion across the lumbosacral junction remains a major challenge. The anatomy of the lumbosacral junction allows for a higher range of motion compared to other areas of the thoracolumbar spine. The L5-S1 interspace is exposed to significant shear forces. As a result, complications such as pseudoarthrosis, screw pull-out, implant fracture, or sacral fractures can occur. Complications are particularly seen in long fusion constructs ending across the lumbosacral junction. To reduce these complications, various lumbosacral and sacropelvic fixation techniques have been developed and utilized. The current supplement is intended to provide instructional videos that illustrate several current techniques for lumbosacral and sacropelvic fixation. The collection includes techniques for anterior L5-S1 interbody fusion, minimally invasive L5-S1 interbody fusions, lumbosacral pedicle screw placement, sacroiliac fusion, and sacro-alar-iliac screw placement. The authors of the videos in the supplement have provided detailed narration and video illustration to describe the nuances of the various open and minimally invasive techniques for lumbosacral and sacral-pelvic fixation. We are pleased to have such a collection of quality video illustration from experts in the field. It's been our privilege to serve as guest editors for this supplement and we believe that you will enjoy the contents of this supplement. PMID- 27364426 TI - Minimally invasive transforaminal lumbosacral interbody fusion. AB - In minimally invasive spinal fusion surgery, transforaminal lumbar (sacral) interbody fusion (TLIF) is one of the most common procedures that provides both anterior and posterior column support without retraction or violation to the neural structure. Direct and indirect decompression can be done through this single approach. Preoperative plain radiographs and MR scan should be carefully evaluated. This video demonstrates a standard approach for how to perform a minimally invasive transforaminal lumbosacral interbody fusion. The video can be found here: https://youtu.be/bhEeafKJ370 . PMID- 27364427 TI - S-1 and S-2-alar-iliac screw fixation via intraoperative navigation. AB - Adult deformity patients often require fixation to the sacrum and pelvis for construct stability and improved fusion rates. Although certain sacropelvic fixation techniques can be challenging, the availability of intraoperative navigation has made many of these techniques more feasible. In this video case presentation, the authors demonstrate the techniques of S-1 bicortical screw and S-2-alar-iliac screw fixation under intraoperative navigation in a 67-year-old female. This instrumentation placement was part of an overall T-10-pelvis construct for the correction of adult spinal deformity. The video can be found here: https://youtu.be/3HZo-80jQr8 . PMID- 27364428 TI - Minimally invasive L5-S1 oblique lumbar interbody fusion with anterior plate. AB - Lumbar interbody fusion is an important technique for the treatment of degenerative disc disease and degenerative scoliosis. The oblique lumbar interbody fusion (OLIF) establishes a minimally invasive retroperitoneal exposure anterior to the psoas and lumbar plexus. In this video case presentation, the authors demonstrate the techniques of the OLIF at L5-S1 performed on a 69-year old female with degenerative scoliosis as one component of an overall strategy for her deformity correction. The video can be found here: https://youtu.be/VMUYWKLAl0g . PMID- 27364429 TI - Technique and nuances of an S-2 alar iliac screw for lumbosacral fixation in patients with transitional and normal anatomy. AB - S-2 alar iliac (S2AI) screw fixation has recently been recognized as a useful technique for pelvic fixation. The authors demonstrate two cases where S2AI fixation was indicated: one case was a sacral insufficiency fracture following a long-segment fusion in a patient with a transitional S-1 vertebra; the other case involved pseudarthrosis following lumbosacral fixation. S2AI screws offer rigid fixation, low profile, and allow easy connection to the lumbosacral rod. The authors describe and demonstrate the surgical technique and nuances for the S2AI screw in a case with transitional S-1 anatomy and in a case with normal S-1 anatomy. The video can be found here: https://youtu.be/Sj21lk13_aw . PMID- 27364430 TI - Advances and challenges in deformable image registration: From image fusion to complex motion modelling. AB - Over the past 20 years, the field of medical image registration has significantly advanced from multi-modal image fusion to highly non-linear, deformable image registration for a wide range of medical applications and imaging modalities, involving the compensation and analysis of physiological organ motion or of tissue changes due to growth or disease patterns. While the original focus of image registration has predominantly been on correcting for rigid-body motion of brain image volumes acquired at different scanning sessions, often with different modalities, the advent of dedicated longitudinal and cross-sectional brain studies soon necessitated the development of more sophisticated methods that are able to detect and measure local structural or functional changes, or group differences. Moving outside of the brain, cine imaging and dynamic imaging required the development of deformable image registration to directly measure or compensate for local tissue motion. Since then, deformable image registration has become a general enabling technology. In this work we will present our own contributions to the state-of-the-art in deformable multi-modal fusion and complex motion modelling, and then discuss remaining challenges and provide future perspectives to the field. PMID- 27364431 TI - Oncological image analysis. AB - Cancer is one of the world's major healthcare challenges and, as such, an important application of medical image analysis. After a brief introduction to cancer, we summarise some of the major developments in oncological image analysis over the past 20 years, but concentrating those in the authors' laboratories, and then outline opportunities and challenges for the next decade. PMID- 27364432 TI - ? PMID- 27364433 TI - Effects of perinatal protein malnutrition and fenfluramine action on food intake and neuronal activation in the hypothalamus and raphe nuclei of neonate rats. AB - In neonatal rats, hunger and satiety responses occur particularly via dehydration and gastric distention, respectively. The control of food intake in newborns is yet to be fully consolidated, particularly with respect to the participation of the hypothalamic nuclei and their relationship with the serotonergic pathway. Moreover, it is unclear how the environmental stressors in early life, like undernutrition, interfere in these events. Therefore, this study examined the serotonin-system's impact on food intake in rat neonates at postnatal day (P) 10 and P18 and the manner in which protein undernutrition during pregnancy and lactation interferes in this behavior. To accomplish this, Wistar rats were used, nutritionally manipulated by a diet having two protein levels, (8% and 17%) during pregnancy and lactation, to form the Control (n=10) and Low protein groups (n=10). At 10 and 18 postnatal days pups received an acute dose of fenfluramine (3mg/kg) or saline (0.9% NaCl) and subjected to milk consumption testing and then perfused to obtain the brains for the analysis of cell activation of the immunoreactive c-Fos in the hypothalamic and raphe nuclei. At 10days a reduction in weight gain was observed in both groups. On comparison of the neuronal activation for the paraventricular nucleus, an increased activation in response to fenfluramine was observed. At 18days, the weight gain percentage differed between the groups according to the nutritional manipulation, in which the control animals had no significant change while the undernourished presented increased weight gain with the use of fenfluramine. The marking of c-Fos in response to fenfluramine in the hypothalamic and raphe nuclei revealed, an especially lower activation of the PVN, MnR and DR compared intra-group. However when evaluating the effect of undernutrition, marking activation was observed to increase in all the nuclei analyzed, in the hypothalamus and raphe. Data from this study indicate that the action of serotonin via food intake in the neonates may have been delayed by early protein undernutrition. PMID- 27364458 TI - The wheat R2R3-MYB transcription factor TaRIM1 participates in resistance response against the pathogen Rhizoctonia cerealis infection through regulating defense genes. AB - The necrotrophic fungus Rhizoctonia cerealis is a major pathogen of sharp eyespot that is a devastating disease of wheat (Triticum aestivum). Little is known about roles of MYB genes in wheat defense response to R. cerealis. In this study, TaRIM1, a R. cerealis-induced wheat MYB gene, was identified by transcriptome analysis, then cloned from resistant wheat CI12633, and its function and preliminary mechanism were studied. Sequence analysis showed that TaRIM1 encodes a R2R3-MYB transcription factor with transcription-activation activity. The molecular-biological assays revealed that the TaRIM1 protein localizes to nuclear and can bind to five MYB-binding site cis-elements. Functional dissection results showed that following R. cerealis inoculation, TaRIM1 silencing impaired the resistance of wheat CI12633, whereas TaRIM1 overexpression significantly increased resistance of transgenic wheat compared with susceptible recipient. TaRIM1 positively regulated the expression of five defense genes (Defensin, PR10, PR17c, nsLTP1, and chitinase1) possibly through binding to MYB-binding sites in their promoters. These results suggest that the R2R3-MYB transcription factor TaRIM1 positively regulates resistance response to R. cerealis infection through modulating the expression of a range of defense genes, and that TaRIM1 is a candidate gene to improve sharp eyespot resistance in wheat. PMID- 27364460 TI - In Vivo Performance of Fenofibrate Formulated With Ordered Mesoporous Silica Versus 2-Marketed Formulations: A Comparative Bioavailability Study in Beagle Dogs. AB - The present study aims to evaluate the in vitro and in vivo performance of ordered mesoporous silica (OMS) as a carrier for the poorly water-soluble compound fenofibrate. Fenofibrate was loaded into OMS via incipient wetness impregnation to obtain a 29% drug load and formulated into capsules. Two capsule dosage forms (containing 33.5 and 16.75 mg fenofibrate, respectively) were compared with the commercially available forms-Lipanthyl((r)) (fenofibrate microcrystals) and Tricor((r)) (fenofibrate nanocrystals). In vitro dissolution tests showed that the amount of fenofibrate released from Lipanthyl((r)) and Tricor((r)) was approximately 30%, whereas approximately 66% and 60% of the drug was released from OMS capsules containing 33.5 and 16.75 mg of fenofibrate, respectively. Storage of OMS capsules loaded with 33.5 mg of fenofibrate at 25 degrees C/60% relative humidity (RH) or 40 degrees C/75% RH did not alter the release kinetics, nor the physical state of the compound, pointing the stability of the present formulation. The in vivo study in dogs confirmed satisfying level of safety and tolerability of fenofibrate-OMS formulation (eq. 33.5 mg) with the potential to improve the absorption of fenofibrate. Though some variability in the data, this formulation is promising to be further investigated in a clinical trial setting. PMID- 27364459 TI - The translationally relevant mouse model of the 15q13.3 microdeletion syndrome reveals deficits in neuronal spike firing matching clinical neurophysiological biomarkers seen in schizophrenia. AB - AIM: To date, the understanding and development of novel treatments for mental illness is hampered by inadequate animal models. For instance, it is unclear to what extent commonly used behavioural tests in animals can inform us on the mental and affective aspects of schizophrenia. METHODS: To link pathophysiological processes in an animal model to clinical findings, we have here utilized the recently developed Df(h15q13)/+ mouse model for detailed investigations of cortical neuronal engagement during pre-attentive processing of auditory information from two back-translational auditory paradigms. We also investigate if compromised putative fast-spiking interneurone (FSI) function can be restored through pharmacological intervention using the Kv3.1 channel opener RE1. Chronic multi-array electrodes in primary auditory cortex were used to record single cell firing from putative pyramidal and FSI in awake animals during processing of auditory sensory information. RESULTS: We find a decreased amplitude in the response to auditory stimuli and reduced recruitment of neurones to fast steady-state gamma oscillatory activity. These results resemble encephalography recordings in patients with schizophrenia. Furthermore, the probability of interneurones to fire with low interspike intervals during 80 Hz auditory stimulation was reduced in Df(h15q13)/+ mice, an effect that was partially reversed by the Kv3.1 channel modulator, RE1. CONCLUSION: This study offers insight into the consequences on a neuronal level of carrying the 15q13.3 microdeletion. Furthermore, it points to deficient functioning of interneurones as a potential pathophysiological mechanism in schizophrenia and suggests a therapeutic potential of Kv3.1 channel openers. PMID- 27364461 TI - Characterizing Reversible Protein Association at Moderately High Concentration Via Composition-Gradient Static Light Scattering. AB - Analysis of weakly self-associating macromolecules at concentrations beyond a few g/L is challenging on account of the confounding effect of thermodynamic nonideality on the association signal. When the reversible association comprises only 1 or 2 oligomeric species in equilibrium with the monomer, the nonideality may be accounted for in a relatively rigorous manner, but if more association states are involved, the analysis becomes quite complex. We show that under reasonable assumptions, the nonideality in a composition-gradient static light scattering measurement may be accounted for in a simple fashion. The correction is applied to determining the stoichiometry and binding affinity of a protein previously characterized via sedimentation equilibrium and dynamic light scattering. The results of the new analysis are remarkably self-consistent and in line with the expectations for the form of self-association predicted previously from analysis of the surface residuals, establishing composition-gradient multi angle static light scattering with nonideality corrections as a critical technology for characterizing associative interactions in concentrated solutions. PMID- 27364462 TI - Water Determination in Solid Pharmaceutical Products Utilizing Ionic Liquids and Headspace Gas Chromatography. AB - A rapid, accurate, and precise headspace gas chromatographic (HSGC) analytical method was developed for the detection and quantification of water in drug products. The analysis is able to be performed in 10 min and automated. The HSGC method used an ionic liquid (IL) based open tubular capillary gas chromatographic column to increase the ruggedness of this method and provide improved peak shapes for water. Due to the ionic liquids low vapor pressure, unique physiochemical properties, and high thermal stability, they also make idea solvents for HSGC. Unlike Karl Fischer titration methods, this HSGC method is not affected by side reactions. The developed method was shown to be broadly applicable. The water content in 12 different samples was found to range from 1%-7% water. The use of HSGC was highly sensitive and only required 10 mg of sample. In addition, it was found to have greater precision and accuracy than Karl Fischer titration and greater precision and speed than loss on drying. PMID- 27364464 TI - Multifaceted toxicity assessment of catalyst composites in transgenic zebrafish embryos. AB - Recent development in the field of nanomaterials has given rise into the inquiries regarding the toxicological characteristics of the nanomaterials. While many individual nanomaterials have been screened for their toxicological effects, composites that accompany nanomaterials are not common subjects to such screening through toxicological assessment. One of the widely used composites that accompany nanomaterials is catalyst composite used to reduce air pollution, which was selected as a target composite with nanomaterials for the multifaceted toxicological assessment. As existing studies did not possess any significant data regarding such catalyst composites, this study focuses on investigating toxicological characteristics of catalyst composites from various angles in both in-vitro and in-vivo settings. Initial toxicological assessment on catalyst composites was conducted using HUVECs for cell viability assays, and subsequent in-vivo assay regarding their direct influence on living organisms was done. The zebrafish embryo and its transgenic lines were used in the in-vivo assays to obtain multifaceted analytic results. Data obtained from the in-vivo assays include blood vessel formation, mutated heart morphology, and heart functionality change. Our multifaceted toxicological assessment pointed out that chemical composites augmented with nanomaterials can too have toxicological threat as much as individual nanomaterials do and alarms us with their danger. This manuscript provides a multifaceted assessment for composites augmented with nanomaterials, of which their toxicological threats have been overlooked. PMID- 27364463 TI - Nanocomposite Hydrogels as Platform for Cells Growth, Proliferation, and Chemotaxis. AB - The challenge of mimicking the extracellular matrix with artificial scaffolds that are able to reduce immunoresponse is still unmet. Recent findings have shown that mesenchymal stem cells (MSC) infiltrating into the implanted scaffold have effects on the implant integration by improving the healing process. Toward this aim, a novel polyamidoamine-based nanocomposite hydrogel is synthesized, cross linked with porous nanomaterials (i.e., mesoporous silica nanoparticles), able to release chemokine proteins. A comprehensive viscoelasticity study confirms that the hydrogel provides optimal structural support for MSC infiltration and proliferation. The efficiency of this hydrogel, containing the chemoattractant stromal cell-derived factor 1alpha (SDF-1alpha), in promoting MSC migration in vitro is demonstrated. Finally, subcutaneous implantation of SDF-1alpha-releasing hydrogels in mice results in a modulation of the inflammatory reaction. Overall, the proposed SDF-1alpha-nanocomposite hydrogel proves to have potential for applications in tissue engineering. PMID- 27364465 TI - Carbon species in PM10 particle fraction at different monitoring sites. AB - The aim of this study was to determine and compare the levels of elemental carbon (EC), organic carbon (OC) and polycyclic aromatic hydrocarbons (PAHs) mass concentrations in PM10 particles (particles with aerodynamic diameter less than 10 MUm) between seasons (winter and summer) and at different monitoring sites (urban background and rural industrial). Daily samples of airborne particles were collected on pre-fired quartz fibre filters. PM10 mass concentrations were determined gravimetrically. Samples were analysed for OC and EC with the thermal/optical transmittance method (TOT) and for PAHs by high-performance liquid chromatography (HPLC) with a fluorescence detector. Measurements showed seasonal and spatial variations of mass concentrations for carbon species and for all of the measured PAHs (Flu, Pyr, Chry, BaA, BbF, BaP, BkF, BghiP and IP) in PM10 at the urban site and rural monitoring site described here. Diagnostic PAH ratios (Flu/(Flu + Pyr), BaA/(BaA + Cry), IP/(IP + BghiP), BaP/BghiP, IP/BghiP and BaP/(BaP + Chry)) make it possible to assess the sources of pollution, and these showed that diesel vehicles accounted for most pollution at the rural industrial (RI) site in the summer, whereas coal and wood combustion were the causes of winter pollution. This difference between winter and summer PAH ratios were more expressed at the RI site than at the UB site because at the UB site the predominant heating fuel was gas. The OC/EC ratio yielded the same conclusion. Factor analysis showed that EC and OC originated from traffic at both sites, PAHs with 5 or more benzene rings originated from wood pellets industry or biomass burning, while Pyr and Flu originated from diesel combustion or as a consequence of different atmospheric behaviour - evaporation and participation in oxidation and photo oxidation processes. PMID- 27364466 TI - Changes in the concentrations of somatic cell counts, lingual antimicrobial peptide and lactoperoxidase activity in milk at periovulatory period in dairy cows. AB - The objective of the present study was to examine the changes in innate immune factors in milk during the estrous cycle in dairy cows. Milk was collected from cows with a normal ovulatory cycle and cows subjected to the OVSYNCH protocol, and somatic cell counts (SCC), lingual antimicrobial peptide (LAP) concentrations and lactoperoxidase (LPO) activity in milk were measured. In cows with a normal ovulatory cycle, there was no significant change in LAP concentrations and SCC during the ovulatory cycle. However, LPO activity at days 0 and 19 (day 0 = day of ovulation) were significantly higher than those at days 10, 12 and 15. In cows subjected to the OVSYNCH protocol, a significant increase in SCC was observed at day 9 (2 days after prostaglandin treatment) compared with that at day 11 (2 days after second administration of gonadotropin). There were no significant changes in LAP concentrations and LPO activity during the OVSYNCH protocol. These results indicate that LPO activity, an innate immune factor, was enhanced in the preovulatory period. PMID- 27364467 TI - The Wnt pathway limits BMP signaling outside of the germline stem cell niche in Drosophila ovaries. AB - The mechanisms that modulate and limit the signaling output of adult stem cell niches remain poorly understood. To gain further insights into how these microenvironments are regulated in vivo, we performed a candidate gene screen designed to identify factors that restrict BMP signal production to the cap cells that comprise the germline stem cell (GSC) niche of Drosophila ovaries. Through these efforts, we found that disruption of Wnt4 and components of the canonical Wnt pathway results in a complex germ cell phenotype marked by an expansion of GSC-like cells, pre-cystoblasts and cystoblasts in young females. This phenotype correlates with an increase of decapentaplegic (dpp) mRNA levels within escort cells and varying levels of BMP responsiveness in the germline. Further genetic experiments show that Wnt4, which exhibits graded expression in somatic cells of germaria, activates the Wnt pathway in posteriorly positioned escort cells. The activation of the Wnt pathway appears to be limited by the BMP pathway itself, as loss of Mad in escort cells results in the expansion of Wnt pathway activation. Wnt pathway activity changes within germaria during the course of aging, coincident with changes in dpp production. These data suggest that mutual antagonism between the BMP and Wnt pathways in somatic cells helps to regulate germ cell differentiation. PMID- 27364469 TI - Organoids from adult liver and pancreas: Stem cell biology and biomedical utility. AB - The liver and pancreas are critical organs maintaining whole body metabolism. Historically, the expansion of adult-derived cells from these organs in vitro has proven challenging and this in turn has hampered studies of liver and pancreas stem cell biology, as well as being a roadblock to disease modelling and cell replacement therapies for pathologies in these organs. Recently, defined culture conditions have been described which allow the in vitro culture and manipulation of adult-derived liver and pancreatic material. Here we review these systems and assess their physiological relevance, as well as their potential utility in biomedicine. PMID- 27364468 TI - Noggin is required for first pharyngeal arch differentiation in the frog Xenopus tropicalis. AB - The dorsal ventral axis of vertebrates requires high BMP activity for ventral development and inhibition of BMP activity for dorsal development. Presumptive dorsal regions of the embryo are protected from the ventralizing activity of BMPs by the secretion of BMP antagonists from the mesoderm. Noggin, one such antagonist, binds BMP ligands and prevents them from binding their receptors, however, a unique role for Noggin in amphibian development has remained unclear. Previously, we used zinc-finger nucleases to mutagenize the noggin locus in Xenopus tropicalis. Here, we report on the phenotype of noggin mutant frogs as a result of breeding null mutations to homozygosity. Early homozygous noggin mutant embryos are indistinguishable from wildtype siblings, with normal neural induction and neural tube closure. However, in late tadpole stages mutants present severe ventral craniofacial defects, notably a fusion of Meckel's cartilage to the palatoquadrate cartilage. Consistent with a noggin loss-of function, mutants show expansions of BMP target gene expression and the mutant phenotype can be rescued with transient BMP inhibition. These results demonstrate that in amphibians, Noggin is dispensable for early embryonic patterning but is critical for cranial skeletogenesis. PMID- 27364470 TI - Reverse engineering liver buds through self-driven condensation and organization towards medical application. AB - The self-organizing tissue-based approach coupled with induced pluripotent stem (iPS) cell technology is evolving as a promising field for designing organoids in culture and is expected to achieve valuable practical outcomes in regenerative medicine and drug development. Organoids show properties of functional organs and represent an alternative to cell models in conventional two-dimensional differentiation platforms; moreover, organoids can be used to investigate mechanisms of development and disease, drug discovery and toxicity assessment. Towards a more complex and advanced organoid model, it is essential to incorporate multiple cell lineages including developing vessels. Using a self condensation method, we recently demonstrated self-organizing "organ buds" of diverse systems together with human mesenchymal and endothelial progenitors, proposing a new reverse engineering method to generate a more complex organoid structure. In this section, we review characters of organ bud technology based on two important principles: self-condensation and self-organization focusing on liver bud as an example, and discuss their practicality in regenerative medicine and potential as research tools for developmental biology and drug discovery. PMID- 27364472 TI - Connectome sensitivity or specificity: which is more important? AB - Connectomes with high sensitivity and high specificity are unattainable with current axonal fiber reconstruction methods, particularly at the macro-scale afforded by magnetic resonance imaging. Tensor-guided deterministic tractography yields sparse connectomes that are incomplete and contain false negatives (FNs), whereas probabilistic methods steered by crossing-fiber models yield dense connectomes, often with low specificity due to false positives (FPs). Densely reconstructed probabilistic connectomes are typically thresholded to improve specificity at the cost of a reduction in sensitivity. What is the optimal tradeoff between connectome sensitivity and specificity? We show empirically and theoretically that specificity is paramount. Our evaluations of the impact of FPs and FNs on empirical connectomes indicate that specificity is at least twice as important as sensitivity when estimating key properties of brain networks, including topological measures of network clustering, network efficiency and network modularity. Our asymptotic analysis of small-world networks with idealized modular structure reveals that as the number of nodes grows, specificity becomes exactly twice as important as sensitivity to the estimation of the clustering coefficient. For the estimation of network efficiency, the relative importance of specificity grows linearly with the number of nodes. The greater importance of specificity is due to FPs occurring more prevalently between network modules rather than within them. These spurious inter-modular connections have a dramatic impact on network topology. We argue that efforts to maximize the sensitivity of connectome reconstruction should be realigned with the need to map brain networks with high specificity. PMID- 27364471 TI - Krupple-like factors 7 and 6a mRNA expression in adult zebrafish central nervous system. AB - Krupple-like factors (KLFs) are transcription factors with zinc finger DNA binding domains known to play important roles in brain development and central nervous system (CNS) regeneration. There is little information on KLFs expression in adult vertebrate CNS. In this study, we used in situ hybridization to examine Klf7 mRNA (klf7) and Klf6a mRNA (klf6a) expression in adult zebrafish CNS. Both klfs exhibit wide and similar expression in the zebrafish CNS. Brain areas containing strongly labeled cells include the ventricular regions of the dorsomedial telencephalon, the ventromedial telencephalon, periventricular regions of the thalamus and hypothalamus, torus longitudinalis, stratum periventriculare of the optic tectum, granular regions of the cerebellar body and valvula, and superficial layers of the facial and vagal lobes. In the spinal cord, klf7- and klf6a-expressing cells are found in both the dorsal and ventral horns. Numerous sensory structures (e.g. auditory, lateral line, olfactory and visual) and several motor nuclei (e.g. oculomotor, trigeminal, and vagal motor nuclei) contain klf7- and/or klf6a-expressing cells. Our results may provide useful information for determining these Klfs in maintenance and/or function in adult CNS. PMID- 27364473 TI - Lamina-dependent calibrated BOLD response in human primary motor cortex. AB - Disentangling neural activity at different cortical depths during a functional task has recently generated growing interest, since this would allow to separate feedforward and feedback activity. The majority of layer-dependent studies have, so far, relied on gradient-recalled echo (GRE) blood-oxygenation-level dependent (BOLD) acquisitions, which are weighted towards the large draining veins at the cortical surface. The current study aims to obtain quantitative brain activity responses in the primary motor cortex on a laminar scale without the contamination due to accompanying secondary vascular effects. Evoked oxidative metabolism was evaluated using the Davis model, to investigate its applicability, advantages, and limits in lamina-dependent fMRI. Average values for the calibration parameter, M, and for changes in the cerebral metabolic rate of oxygen consumption (CMRO2) during a unilateral finger-tapping task were (11+/-2)% and (30+/-7)%, respectively, with distinct variation features across the cortical depth. The results presented here showed an uncoupling between BOLD-based functional magnetic resonance imaging (fMRI) and metabolic changes across cortical depth, while the tight coupling between CMRO2 and CBV was conserved across cortical layers. We conclude that the Davis model can help to obtain estimates of lamina-dependent metabolic changes without contamination from large draining veins, with high consistency and reproducibility across participants. PMID- 27364474 TI - A regularized full reference tissue model for PET neuroreceptor mapping. AB - The full reference tissue model (FRTM) is a PET analysis framework that includes both free and specifically bound compartments within tissues, together with rate constants defining association and dissociation from the specifically bound compartment. The simplified reference tissue model (SRTM) assumes instantaneous exchange between tissue compartments, and this "1-tissue" approximation reduces the number of parameters and enables more robust mapping of non-displaceable binding potentials. Simulations based upon FRTM have shown that SRTM exhibits biases that are spatially dependent, because biases depend upon binding potentials. In this work, we describe a regularized model (rFRTM) that employs a global estimate of the dissociation rate constant from the specifically bound compartment (k4). The model provides an internal calibration for optimizing k4 through the reference-region outflow rate k2', a model parameter that should be a global constant but varies regionally in SRTM. Estimates of k4 by rFRTM are presented for four PET radioligands. We show that SRTM introduces bias in parameter estimates by assuming an infinite value for k4, and that rFRTM ameliorates bias with an appropriate choice of k4. Theoretical considerations and simulations demonstrate that rFRTM reduces bias in non-displaceable binding potentials. A two-parameter reduction of the model (rFRTM2) provides robust mapping at a voxel-wise level. With a structure similar to SRTM, the model is easily implemented and can be applied as a PET reference region analysis that reduces parameter bias without substantially altering parameter variance. PMID- 27364475 TI - Super-Resonant Intracavity Coherent Absorption. AB - The capability of optical resonators to extend the effective radiation-matter interaction length originates from a multipass effect, hence is intrinsically limited by the resonator's quality factor. Here, we show that this constraint can be overcome by combining the concepts of resonant interaction and coherent perfect absorption (CPA). We demonstrate and investigate super-resonant coherent absorption in a coupled Fabry-Perot (FP)/ring cavity structure. At the FP resonant wavelengths, the described phenomenon gives rise to split modes with a nearly-transparent peak and a peak whose transmission is exceptionally sensitive to the intracavity loss. For small losses, the effective interaction pathlength of these modes is proportional respectively to the ratio and the product of the individual finesse coefficients of the two resonators. The results presented extend the conventional definition of resonant absorption and point to a way of circumventing the technological limitations of ultrahigh-quality resonators in spectroscopy and optical sensing schemes. PMID- 27364476 TI - Endocytic Control of Cellular Signaling at the Primary Cilium. AB - Primary cilia are dynamic signaling organelles that project from the cell surface to sense diverse chemical, physical and morphogenetic cues. Ciliary defects therefore cause diseases (ciliopathies) that affect multiple organs in developing and adult organisms. Cilia-mediated signaling involves the orchestrated movement of signaling proteins in and out of the ciliary compartment, including movement of receptors such as the Sonic Hedgehog (Shh) receptor Patched 1 (PTCH1), Smoothened (SMO), and various other G protein-coupled receptors (GPCRs), as well as transforming growth factor beta (TGF-beta) receptors I and II (TGF-beta RI/II). We provide here a current understanding of trafficking events associated with cilia-mediated signaling, with emphasis on the involvement of clathrin dependent receptor-mediated endocytosis in regulating ciliary Shh and TGF-beta signaling. PMID- 27364477 TI - Role of Ionic Strength in Staphylococcal Cell Aggregation. AB - Cell aggregation plays a key role in biofilm formation and pathogenesis of Staphylococcus species. Although the molecular basis of aggregation in Staphylococci has already been extensively investigated, the influence of environmental factors, such as ionic strength, remains poorly understood. In this paper, we report a new type of cellular aggregation of Staphylococci that depends solely on ionic strength. Seven strains out of 14, all belonging to staphylococcal species, formed large cell clusters within minutes in buffers of ionic strength ranging from 1.5 to 50 mM, whereas isolates belonging to other Gram-positive species did not display this phenotype. Atomic force microscopy (AFM) with chemically functionalized tips provided direct evidence that ionic strength modulates cell surface adhesive properties through changes in cell surface charge. The optimal ionic strength for aggregation was found to be strain dependent, but in all cases, bacterial aggregates formed at an ionic strength of 1.5-50 mM were rapidly dispersed in a solution of higher ionic strength, indicating a reversibility of the cell aggregation process. These findings suggest that some staphylococcal isolates can respond to ionic strength as an external stimulus to trigger rapid cell aggregation in a way that has not yet been reported. PMID- 27364478 TI - TRPV4 is associated with central rather than nephrogenic osmoregulation. AB - TRPV4 is a polymodal cation channel expressed in osmosensitive neurons of the hypothalamus and in the mammalian nephron. The segmental distribution and role(s) of TRPV4 in osmoregulation remain debated. We investigated the renal distribution pattern of TRPV4 and the functional consequences of its disruption in mouse models. Using qPCR on microdissected segments, immunohistochemistry, and a LacZ reporter mouse, we found that TRPV4 is abundantly expressed in the proximal tubule, the late distal convoluted tubule, and throughout the connecting tubule and collecting duct, including principal and intercalated cells. TRPV4 was undetectable in the glomeruli and thick ascending limb and weakly abundant in the early distal convoluted tubule. Metabolic studies in Trpv4 (+/+) and Trpv4 (-/-) littermates revealed that the lack of TRPV4 did not influence activity, food and water intake, renal function, and urinary concentration at baseline. The mice showed a similar response to furosemide, water loading and deprivation, acid loading, and dietary NaCl restriction. However, Trpv4 (-/-) mice showed a significantly lower vasopressin synthesis and release after water deprivation, with a loss of the positive correlation between plasma osmolality and plasma vasopressin levels, and a delayed water intake upon acute administration of hypertonic saline. Specific activation of TRPV4 in primary cultures of proximal tubule cells increased albumin uptake, whereas no effect of TRPV4 deletion could be observed at baseline. These data reveal that, despite its abundant expression in tubular segments, TRPV4 does not play a major role in the kidney or is efficiently compensated when deleted. Instead, TRPV4 is critical for the release of vasopressin, the sensation of thirst, and the central osmoregulation. PMID- 27364480 TI - Hypomagnesemia in Pediatric Heart Transplant Patients Treated with Tacrolimus. AB - OBJECTIVES: We aimed to investigate the frequency of hypomagnesemia and urinary magnesium excretion in pediatric heart transplant recipients. MATERIALS AND METHODS: In this study, 22 pediatric patients who underwent heart transplanted at a single center between March 2014 and April 2015 and who were treated with oral tacrolimus were analyzed prospectively. Serum magnesium, creatinine, and tacrolimus levels and total amount of urinary magnesium excretion were measured. Serum tacrolimus levels were measured 12 hours after the last dose of tacrolimus. RESULTS: Our patient group included 11 boys (50%) and 11 girls (50%) with a mean age of 16.72 +/- 4.78 years. Serum tacrolimus levels were in the therapeutic range, with a mean of 1.48 +/- 0.13 ng/mL (range, 1.2-1.69 ng /mL), mean fractional magnesium excretion was 8.59 +/- 5.9% (range, 3%-22%), and 24-hour urinary magnesium excretion was 90.2 +/- 62.95 mg/d. Hypermagnesuria was assessed in 80% of patients. We found 24-hour urinary magnesium excretion to be higher than normal in 27% of patients. There was no association between serum tacrolimus levels and serum magnesium levels or urinary magnesium excretion. CONCLUSIONS: Serum magnesium levels should be periodically measured in pediatric heart transplant patients treated with tacrolimus. PMID- 27364479 TI - Negative regulation and developmental competence in Aspergillus. AB - Asexual development (conidiation) in the filamentous fungus Aspergillus nidulans is governed by orchestrated gene expression. The three key negative regulators of conidiation SfgA, VosA, and NsdD act at different control point in the developmental genetic cascade. Here, we have revealed that NsdD is a key repressor affecting the quantity of asexual spores in Aspergillus. Moreover, nullifying both nsdD and vosA results in abundant formation of the development specific structure conidiophores even at 12 h of liquid culture, and near constitutive activation of conidiation, indicating that acquisition of developmental competence involves the removal of negative regulation exerted by both NsdD and VosA. NsdD's role in repressing conidiation is conserved in other aspergilli, as deleting nsdD causes enhanced and precocious activation of conidiation in Aspergillus fumigatus or Aspergillus flavus. In vivo NsdD-DNA interaction analyses identify three NsdD binding regions in the promoter of the essential activator of conidiation brlA, indicating a direct repressive role of NsdD in conidiation. Importantly, loss of flbC or flbD encoding upstream activators of brlA in the absence of nsdD results in delayed activation of brlA, suggesting distinct positive roles of FlbC and FlbD in conidiation. A genetic model depicting regulation of conidiation in A. nidulans is presented. PMID- 27364481 TI - The role of enhancers in cancer. AB - Enhancer elements function as the logic gates of the genetic regulatory circuitry. One of their most important functions is the integration of extracellular signals with intracellular cell fate information to generate cell type-specific transcriptional responses. Mutations occurring in cancer often misregulate enhancers that normally control the signal-dependent expression of growth-related genes. This misregulation can result from trans-acting mechanisms, such as activation of the transcription factors or epigenetic regulators that control enhancer activity, or can be caused in cis by direct mutations that alter the activity of the enhancer or its target gene specificity. These processes can generate tumour type-specific super-enhancers and establish a 'locked' gene regulatory state that drives the uncontrolled proliferation of cancer cells. Here, we review the role of enhancers in cancer, and their potential as therapeutic targets. PMID- 27364482 TI - A fate worse than death: apoptosis as an oncogenic process. AB - Apoptotic cell death is widely considered a positive process that both prevents and treats cancer. Although undoubtedly having a beneficial role, paradoxically, apoptosis can also cause unwanted effects that may even promote cancer. In this Opinion article we highlight some of the ways by which apoptosis can exert oncogenic functions. We argue that fully understanding this dark side will be required to optimally engage apoptosis, thereby maximizing tumour cell kill while minimizing unwanted pro-tumorigenic effects. PMID- 27364483 TI - Altered Functional Magnetic Resonance Imaging Markers of Affective Processing During Treatment of Late-Life Depression. AB - OBJECTIVE: This study investigated neural substrate changes in affective processing among late-life depression (LLD) patients undergoing antidepressant treatment and determined if these changes correlated with remission status. METHODS: Thirty-three LLD patients were enrolled in a 12-week venlafaxine treatment course. During treatment functional magnetic resonance imaging (fMRI) scans, paired with an affective task that assessed emotional reactivity and regulation, were performed on days 1, 2, 3, and 7 and at week 12. Following treatment patients were classified as remitters or non-remitters. A voxel-wise two-way repeated-measures ANOVA was performed to assess the fMRI data at a significance level of alpha = 0.05, corrected. RESULTS: The emotional reactivity contrast demonstrated a significant interaction between remission status and scan time in the right middle temporal gyrus (MTG) (F = 24.1, df = 1,112, k = 102). Further analysis showed increased emotional reactivity-induced activity among non remitters, and decreased activity among remitters, which significantly differed from baseline at day 7 (95% CI: 0.027, 0.540; Cohen's d = -1.35) and week 12 (95% CI: -0.171, -0.052; Cohen's d = 0.68), respectively. No significant interaction was observed with the emotional regulation contrast, but multiple regions had significant main effects of scan time, including the cuneus, occipital lobe, insula, lingual gyrus, posterior cingulate cortex, and MTG. CONCLUSIONS: During treatment of LLD patients, affective processing-induced activity in the right MTG shows changes based on remission status. This alteration becomes evident early during the course of treatment, suggesting that antidepressant pharmacotherapy may acutely affect the neural basis of emotional reactivity in a differential manner that is relevant to illness remission. PMID- 27364484 TI - The effect of the UV photon flux on the photoelectrocatalytic degradation of endocrine-disrupting alkylphenolic chemicals. AB - The photoelectrocatalytic (PEC) degradation of 4-nonylphenol ethoxylate (NP4EO) using a low, moderate, or high UV photon flux in different treatment times was investigated. The byproducts were verified using gas chromatography with flame ionization detection (GC-FID) and gas chromatography with quadrupole mass analyzer (GC-qMS). The GC results showed that the use of a low (2.89 MUmol m( 2)s(-1)) or a high (36.16 MUmol m(-2)s(-1)) UV photon flux reaching the anode surface was associated to the production of alcohols and the toxic byproduct nonylphenol (NP), leading to the same degradation pathway. Meanwhile, the use of a moderate UV photon flux (14.19 MUmol m(-2)s(-1)) reaching the anode surface did not produce alcohols or the NP toxic byproduct. This study demonstrates that different UV photon fluxes will have an influence in the degradation of NP4EO with or without generation of toxic byproducts. Furthermore, it is concluded that, after the determination of the UV photon flux able to degrade NP4EO without NP formation, the treatment time is essential in removal of NP4EO, since increasing the treatment time of 4 to 10 h, when using the PEC best conditions (moderate UV photon flux), implies in a higher treatment efficiency. PMID- 27364485 TI - Occurrence and fate of PBDEs and novel brominated flame retardants in a wastewater treatment plant in Harbin, China. AB - Wastewater treatment plant (WWTP) is considered to be an important medium for the transport and transformation of organic pollutants. This study attempted to comprehensively investigate polybrominated diphenyl ethers (PBDEs) and novel brominated flame retardants (NBFRs) in a WWTP in Harbin, one of the main "Old Industrial Base" in China. The mean concentrations of the total PBDEs in the influent, effluent, and sludge were 152 ng/L, 16.2 ng/L, and 503 g/g dw, respectively, which were at the low end of the global range. BDE-209 was the most abundant congener, with contributions to the total PBDE ranging from 90.5 to 98.5 %. The level of the total NBFRs ranged from 24.5 to 107 ng/L, 0.95 to 20.3 ng/L, and 305 to 1202 ng/g dw in the influent, effluent, and sludge, respectively. For NBFRs, DBDPE was the most abundant congener (38.8-50.5 %), followed by BEHTBP (11.0-35.0 %). The ratio for DBDPE/BDE-209 (0.62 +/- 0.42) was found less than 1 in sludge, which indicated that Deca-BDE is still the major BFR product in this city. Source identification suggested that indoor dust should be an important source of BFRs in the WWTP. Approximately 20.8 and 7.79 kg of PBDEs and NBFRs on annual basis were removed with the sludge. Biodegradation could play an important role on the fate of BFRs in the WWTP, which is required for future research. PMID- 27364486 TI - Sympodial bamboo species differ in carbon bio-sequestration and stocks within phytoliths of leaf litters and living leaves. AB - Phytolith-occluded carbon (PhytOC) with high resistance against decomposition is an important carbon (C) sink in many ecosystems. This study compared concentrations of phytolith in plants and the PhytOC production of seven sympodial bamboo species in southern China, aiming to provide the information for the managed bamboo plantation and selection of bamboo species to maximize phytolith C sequestration. Leaf litters and living leaves of seven sympodial bamboo species were collected from the field sites. Concentrations of phytoliths, silicon (Si), and PhytOC in leaf litters and living leaves were measured. Carbon sequestration as PhytOC was estimated. There was a considerable variation in the PhytOC concentrations in the leaf litters and living leaves among the seven bamboo species. The mean concentrations of PhytOC ranged from 3.4 to 6.9 g kg(-1) in leaf litters and from 1.6 to 5.9 g kg(-1) in living leaves, with the PhytOC production rates ranging from 5.7 to 52.3 kg e-CO2 ha(-1) year(-1) as leaf litters. Dendrocalamopsis oldhami (Munro) Keng f. had the highest PhytOC production rate. Based on a bio-sequestration rate of 52.3 kg e-CO2 ha(-1) year( 1), we estimated that the current 8 * 10(5) ha of sympodial bamboo stands in China could potentially acquire 4.2 * 10(4) t e-CO2 yearly via phytolith carbon. Furthermore, the seven sympodial bamboo species stored 5.38 * 10(5) t e-CO2 as PhytOC in living leaves and leaf litters in China. It is concluded that sympodial bamboos make a significant contribution to C sequestration and that to maximize the PhytOC accumulation, the bamboo species with the highest PhytOC production rate should be selected for plantation. PMID- 27364487 TI - Sorption of chlorophenols on microporous minerals: mechanism and influence of metal cations, solution pH, and humic acid. AB - Sorption of 2-chlorophenol (2-CP), 2,4-dichlorophenol (2,4-DCP), and 2,4,6 trichlorophenol (2,4,6-TCP) on a range of dealuminated zeolites were investigated to understand the mechanism of their sorption on microporous minerals, while the influence of common metal cations, solution pH, and humic acid was also studied. Sorption of chlorophenols was found to increase with the hydrophobicity of the sorbates and that of the microporous minerals, indicating the important role of hydrophobic interactions, while sorption was also stronger in the micropores of narrower sizes because of greater enhancement of the dispersion interactions. The presence of metal cations could enhance chlorophenol sorption due to the additional electrostatic attraction between metal cations exchanged into the mineral micropores and the chlorophenolates, and this effect was apparent on the mineral sorbent with a high density of surface cations (2.62 sites/nm(2)) in its micropores. Under circum-neutral or acidic conditions, neutral chlorophenol molecules adsorbed into the hydrophobic micropores through displacing the "loosely bound" water molecules, while their sorption was negligible under moderately alkaline conditions due to electrostatic repulsion between the negatively charged zeolite framework and anionic chlorophenolates. The influence of humic acid on sorption of chlorophenols on dealuminated Y zeolites suggests that its molecules did not block the micropores but created a secondary sorption sites by forming a "coating layer" on the external surface of the zeolites. These mechanistic insights could help better understand the interactions of ionizable chlorophenols and metal cations in mineral micropores and guide the selection and design of reusable microporous mineral sorbents for sorptive removal of chlorophenols from aqueous stream. PMID- 27364488 TI - Effect of deflocculation on the efficiency of sludge reduction by Fenton process. AB - A novel approach to improve the efficiency of Fenton treatment for sludge reduction through the implication of a deflocculating agent citric acid, for the exclusion of extracellular polymeric substances (EPS) from waste-activated sludge (WAS), was investigated. Deflocculation was achieved with 0.06 g/g suspended solids (SS) of citric acid dosage. Fenton optimization studies using response surface methodology (RSM) revealed that 0.5 and 0.0055 g/g SS were the optimal dosages of H2O2 and Fe(2+). The addition of a cation-binding agent set the pH value of sludge to 5 which did not affect the Fenton efficiency. The results presented in this study shows the advantage of deflocculating the sludge as SS and volatile suspended solids (VSS) reductions were found to be higher in the deflocculated (53 and 63 %, respectively) than in the flocculated (22 and 34 %, respectively) sludges. Kinetic investigation of the treatment showed that the rate of the reaction was four times higher in the deflocculated sludge than control. The methodology reported in this manuscript was successfully applied to a real case were the deflocculated mediated Fenton process reduced the sludge disposal cost from 297.8 to 61.9 US dollars/ton of sludge. PMID- 27364489 TI - Photo-assisted electrochemical degradation of simulated textile effluent coupled with simultaneous chlorine photolysis. AB - The influence of chloride ion concentration during the photo-assisted electrochemical degradation of simulated textile effluent, using a commercial Ti/Ru0.3Ti0.7O2 anode, was evaluated. Initially, the effect of applied current and supporting electrolyte concentration on the conversion of chloride ions to form reactive chlorine species in 90 min of experiment was analyzed in order to determine the maximum production of reactive chlorine species. The optimum conditions encountered (1.5 A and 0.3 mol dm(-3) NaCl) were subsequently employed for the degradation of simulated textile effluent. The efficiency of the process was determined through the analysis of chemical oxygen demand (COD), total organic carbon (TOC), of the presence of organochlorine products and phytotoxicity. Photo-assisted electrochemical degradation was more efficient for COD and TOC removal than the electrochemical technique alone. With simultaneous UV irradiation, a reduced quantity of reactive chlorine was produced, indicating that photolysis of the chlorine species led to the formation of hydroxyl radicals. This fact turns a simple electrochemical process into an advanced oxidation process. PMID- 27364490 TI - Evaluation of an innovative approach based on prototype engineered wetland to control and manage boron (B) mine effluent pollution. AB - A major environmental problem associated with boron (B) mining in many parts of the world is B pollution, which can become a point source of B mine effluent pollution to aquatic habitats. In this study, a cost-effective, environment friendly, and sustainable prototype engineered wetland was evaluated and tested to prevent B mine effluent from spilling into adjoining waterways in the largest B reserve in the world. According to the results, average B concentrations in mine effluent significantly decreased from 17.5 to 5.7 mg l(-1) after passing through the prototype with a hydraulic retention time of 14 days. The results of the present experiment, in which different doses of B had been introduced into the prototype, also demonstrated that Typha latifolia (selected as donor species in the prototype) showed a good resistance to alterations against B mine effluent loading rates. Moreover, we found that soil enzymes activities gradually decreased with increasing B dosages during the experiment. Boron mass balance model further showed that 60 % of total B was stored in the filtration media, and only 7 % of B was removed by plant uptake. Consequently, we suggested that application of the prototype in the vicinity of mining site may potentially become an innovative model and integral part of the overall landscape plan of B mine reserve areas worldwide. Graphical Abstract ?. PMID- 27364491 TI - G5, a Phage Single-Stranded DNA-Binding Protein, Fused with a Nuclear Localization Signal, Attenuates Symptoms and Reduces Begomovirus-Betasatellite Accumulation in Transgenic Plants. AB - Cotton leaf curl disease is caused by several monopartite begomoviruses and is the major threat to cotton production in the Indian subcontinent. The disease has been shown to be associated with four distinct species, including Cotton leaf curl Kokhran virus (CLCuKoV), and a specific betasatellite-Cotton leaf curl Multan betasatellite (CLCuMuB). Transgenic Nicotiana benthamiana plants were produced which constitutively express the Escherichia coli phage M13 encoded, sequence nonspecific single-stranded (ss) DNA-binding protein, G5 alone and fused with the maize opaque-2 nuclear localization signal (NLS), to evaluate resistance against CLCuKoV-CLCuMuB. Transgenic plants expressing only G5 performed poorly exhibiting symptoms of infection and high virus DNA levels upon inoculation with CLCuKoV and CLCuKoV with CLCuMuB. In contrast, plants transformed with G5 fused to the NLS developed mild symptoms and showed a reduction in virus and betasatellite DNA levels in comparison to nontransformed plants. The results show that G5 may be useful in developing broad-spectrum resistance against ssDNA viruses. PMID- 27364492 TI - Carotid atherosclerosis is associated with left ventricular diastolic function. AB - BACKGROUND: It has been reported that carotid intima-media thickness (IMT) correlates with the risk of stroke or cardiovascular disease. The purpose of this study was to analyze the relationships between echocardiographic findings and carotid atherosclerosis. METHODS: A total of 234 patients (62 +/- 15 years) were referred for echocardiography to evaluate the left ventricular (LV) function. The LV ejection fraction, the ratio of the peak velocity of early rapid filling and the peak velocity of atrial filling (E/A), and the peak early diastolic mitral annular velocity (e') were obtained by echocardiography. The maximum IMT (Max IMT) and plaque score (PS) were measured by carotid ultrasonography within 1 month of the echocardiographic examination. RESULTS: The mean values of Max-IMT and carotid PS were 2.41 +/- 1.23 mm and 8.5 +/- 6.3, respectively. The decreased mean E/A (0.94 +/- 0.39) and mitral e' (5.5 +/- 1.9 cm/s) indicated LV diastolic dysfunction. A good correlation was observed between Max-IMT and PS (r = 0.83, p < 0.0001). It was shown that 2.8 mm of Max-IMT was equivalent to 10.1 of carotid PS, which indicated severe carotid atherosclerosis. In multiple logistic stepwise regression analysis, among the echocardiographic parameters, only e' was independently associated with severe carotid atherosclerosis (Max-IMT >= 2.8 mm or PS >= 10.1). CONCLUSIONS: The present study demonstrated that decreased early diastolic mitral annular velocity relates to the parameter reflecting carotid atherosclerosis. Therefore, the presence of severe carotid atherosclerosis may affect LV diastolic dysfunction. PMID- 27364493 TI - Shock in the emergency department; a 12 year population based cohort study. AB - BACKGROUND: The knowledge of the frequency and associated mortality of shock in the emergency department (ED) is limited. The aim of this study was to describe the incidence, all-cause mortality and factors associated with death among patients suffering shock in the ED. METHODS: Population-based cohort study at an University Hospital ED in Denmark from January 1, 2000, to December 31, 2011. All patients aged >=18 years living in the hospital catchment area with a first time ED presentation with shock (n = 1646) defined as hypotension (systolic blood pressure (SBP) <=100 mmHg)) and >=1 organ failures. Outcomes were annual incidence per 100,000 person-years at risk (pyar), all-cause mortality at 0-7, and 8-90 days and risk factors associated with death. RESULTS: We identified 1646 of 438,191 (0.4 %) ED patients with shock at arrival. Incidence of shock increased from 53.8 to 80.6 cases per 100,000 pyar. The 7-day, and 90-day mortality was 23.1 % (95 % CI: 21.1-25.1) and 40.7 % (95 % CI: 38.3-43.1), respectively. Independent predictors of 7-day mortality were: age (adjusted HR 1.03 (95 % CI: 1.03-1.04), and number of organ failures (>=3 organ failures; adjusted HR 3.13 95 % CI: 2.28-4.30). Age, comorbidity level and number of organ failure were associated with 90-day mortality. CONCLUSION: Shock is a frequent and critical finding in the ED, carrying a 7- and, 90- day mortality of 23.1 and 40.7 %, respectively. Age and number of organ failures are independent prognostic factors for death within 7 days, whereas age, comorbidity and organ failures are of significance within 8-90 days. PMID- 27364494 TI - Coordinative Amphiphiles as Tunable siRNA Transporters. AB - In this study, we developed coordinative amphiphiles for use as novel siRNA transporters. As a modification of a conventional cationic lipid structure, we replaced the cationic head with zinc(II)-dipicolylamine complex (Zn/DPA) as a phosphate-directing group, and used various membrane-directing groups in the place of the hydrophobic tails. These simple amphiphiles are readily synthesized and easy to modify. The Zn/DPA head groups bind to the phosphate backbones of siRNAs, and to our surprise, they prevented the enzymatic degradation of siRNAs by RNase A. Interestingly, the Zn/DPA head itself exhibited moderate transfection efficiency, and its combination with a membrane-directing group-oleoyl (CA1), pyrenebutyryl (CA2), or biotin (CA3)-enhanced the delivery efficiency without imparting significant cytotoxicity. Notably, the uptake pathway was tunable depending on the nature of the membrane-directing group. CA1 delivered siRNAs mainly through caveolae-mediated endocytosis, and CA2 through clathrin- and caveolin-independent endocytosis; CA3 recruited siRNAs specifically into biotin receptor-positive HepG2 cells through receptor-mediated endocytosis. Thus, it appears possible to develop tunable siRNA transporters simply by changing the membrane-directing parts. These are the first examples of amphiphilic siRNA transporters accompanying coordinative interactions between the amphiphiles and siRNAs. PMID- 27364495 TI - [From myxomas of the skin to LVAD implantation : A 28-year-old female patient with Carney complex]. AB - Multiple skin lesions, endocrine dysfunction and cardiac myxomas are characteristic symptoms of Carney complex. This case report gives an overview about the major and minor criteria of Carney complex and presents the course of a female patient who developed severe cardiac insufficiency with multiple organ failure because of recurring heart operations leading to implantation of a left ventricular assist device (LVAD). PMID- 27364496 TI - Diversification of R2R3-MYB Transcription Factors in the Tomato Family Solanaceae. AB - MYB transcription factors play an important role in regulating key plant developmental processes involving defense, cell shape, pigmentation, and root formation. Within this gene family, sequences containing an R2R3 MYB domain are the most abundant type and exhibit a wide diversity of functions. In this study, we identify 559 R2R3 MYB genes using whole genome data from four species of Solanaceae and reconstruct their evolutionary relationships. We compare the Solanaceae R2R3 MYBs to the well-characterized Arabidopsis thaliana sequences to estimate functional diversity and to identify gains and losses of MYB clades in the Solanaceae. We identify numerous R2R3 MYBs that do not appear closely related to Arabidopsis MYBs, and thus may represent clades of genes that have been lost along the Arabidopsis lineage or gained after the divergence of Rosid and Asterid lineages. Despite differences in the distribution of R2R3 MYBs across functional subgroups and species, the overall size of the R2R3 subfamily has changed relatively little over the roughly 50 million-year history of Solanaceae. We added our information regarding R2R3 MYBs in Solanaceae to other data and performed a meta-analysis to trace the evolution of subfamily size across land plants. The results reveal many shifts in the number of R2R3 genes, including a 54 % increase along the angiosperm stem lineage. The variation in R2R3 subfamily size across land plants is weakly positively correlated with genome size and strongly positively correlated with total number of genes. The retention of such a large number of R2R3 copies over long evolutionary time periods suggests that they have acquired new functions and been maintained by selection. Discovering the nature of this functional diversity will require integrating forward and reverse genetic approaches on an -omics scale. PMID- 27364497 TI - Nasopharyngeal microbiota composition of children is related to the frequency of upper respiratory infection and acute sinusitis. AB - BACKGROUND: Upper respiratory infections (URI) and their complications are a major healthcare burden for pediatric populations. Although the microbiology of the nasopharynx is an important determinant of the complications of URI, little is known of the nasopharyngeal (NP) microbiota of children, the factors that affect its composition, and its precise relationship with URI. RESULTS: Healthy children (n = 47) aged 49-84 months from a prospective cohort study based in Wisconsin, USA, were examined. Demographic and clinical data and NP swab samples were obtained from participants upon entry to the study. All NP samples were profiled for bacterial microbiota using a phylogenetic microarray, and these data were related to demographic characteristics and upper respiratory health outcomes. The composition of the NP bacterial community of children was significantly related prior to the history of acute sinusitis (R (2) = 0.070, P < 0.009). History of acute sinusitis was associated with significant depletion in relative abundance of taxa including Faecalibacterium prausnitzii and Akkermansia spp. and enrichment of Moraxella nonliquefaciens. Enrichment of M. nonliquefaciens was also a characteristic of baseline NP samples of children who subsequently developed acute sinusitis over the 1-year study period. Time to develop URI was significantly positively correlated with NP diversity, and children who experienced more frequent URIs exhibited significantly diminished NP microbiota diversity (P <= 0.05). CONCLUSIONS: These preliminary data suggest that previous history of acute sinusitis influences the composition of the NP microbiota, characterized by a depletion in relative abundance of specific taxa. Diminished diversity was associated with more frequent URIs. PMID- 27364498 TI - Mucocele-Like Lesions of the Breast: Rate of Upstaging and Cancer Development. AB - BACKGROUND: Breast mucocele-like lesions (MLLs) are rare breast lesions. There is a paucity of literature on the rate of pathologic upstaging of MLL to in situ or invasive breast cancer. We sought to review our experience with MLL at a tertiary care center and review published literature. METHODS: A retrospective review was undertaken of all patients with breast MLL at the Mayo Clinic, Rochester, from 1998 to 2016. Descriptive statistics were performed. RESULTS: Overall, 30 patients were diagnosed with MLL, with a mean age of 54.6 years (range 51-58). Calcifications on screening mammogram were the most common method of MLL detection (n = 26, 86.7 %), with core needle biopsy (CNB) being performed in 29/30 patients. MLL with atypia was identified in 14 patients (48 %), and surgical excision was performed in 26 patients. Disease was upstaged to invasive disease in one patient (3.8 %) who presented with a palpable mass. With a median duration of follow up of 3.5 years [interquartile range 1-7.1], two patients developed contralateral invasive breast cancer (both patients had a remote history of invasive breast cancer on that side), and one patient developed contralateral in situ disease. Review of the literature demonstrates a 2.9 % upgrade rate of MLL without atypia on excisional biopsy. CONCLUSIONS: The upstage rate of MLL identified on CNB to invasive disease at surgical excision in this series was 3.8 %. In cases with MLL presenting as calcifications, no cases were upstaged in this series. Across the literature, upstage rates of MLL without atypia on CNB are low, indicating excisional biopsy may be avoided in these cases. PMID- 27364499 TI - High Absolute Monocyte Count Predicts Poor Clinical Outcome in Patients with Castration-Resistant Prostate Cancer Treated with Docetaxel Chemotherapy. AB - BACKGROUND: The association of peripheral monocyte count and prostate cancer progression is not well characterized. OBJECTIVE: Our aim was to investigate the prognostic value of absolute monocyte count (AMC), which is thought to modulate immune response in the tumor microenvironment, in castration-resistant prostate cancer (CRPC) patients treated with docetaxel chemotherapy. METHODS: We retrospectively reviewed the medical records of 214 CRPC patients who received docetaxel therapy and were used as the training and validation set. Docetaxel at a dose of 75 mg/m2 was administered every 3 or 4 weeks. Clinicopathological factors and laboratory data were collected to assess the prognostic factors for overall survival (OS) and progression-free survival (PFS). RESULTS: In the training set, the median age was 73.0 years, and the median prostate-specific antigen (PSA) value was 31.7 ng/ml at initial treatment. The median OS and PFS were 23.0 months (range 1.20-84.0) and 11.2 months (range 3.6-78.0), respectively. According to multivariable Cox regression analysis, AMC >=400/uL, PSA level >=20 ng/ml, and Hb <10 mg/dL were associated with increased risk of PSA progression [hazard ratio (HR) 2.06, p = 0.005; HR 2.39, p = 0.002; and HR 2.38, p = 0.024, respectively]. Moreover, multivariate analysis for OS indicated that AMC >=400/uL, pretreatment PSA level >=20 ng/ml, presence of visceral metastasis, and alkaline phosphatase >=284 U/L were independent prognostic factors for shortened OS (HR 2.07, p = 0.004; HR 2.18, p = 0.007; HR 2.11, p = 0.011; and HR 1.67, p = 0.048, respectively). According to the validation set, high AMC remained an independent prognostic factor for PFS and OS (HR 2.26, p = 0.001; and HR 3.10, p < 0.001, respectively). CONCLUSIONS: Elevated monocyte counts were associated with aggressive tumor features and poor survival outcomes of patients with CRPC treated with docetaxel chemotherapy. PMID- 27364500 TI - Pylorus-Preserving Surgery Based on the Sentinel Node Concept in Early Gastric Cancer. AB - BACKGROUND: In patients with early stage gastric cancer in the middle third of the stomach, pylorus-preserving gastrectomy (PPG) can be an option as function preserving surgery, although its oncologic safety is not definitively defined. This issues may be overcome using the sentinel node (SN) concept. The aim of this study was to investigate the effectiveness of the SN concept in early gastric cancer patients who are candidates for PPG. METHODS: One hundred fifty-six patients with middle-third location of cT1N0 gastric cancer (single lesion, <4 cm) underwent distal gastrectomy with SN mapping. As a tracer, technetium-99 tin colloid solution and blue dye were endoscopically injected into the submucosal layer surrounding the primary tumor. RESULTS: SN detection rate was 100 % (156 of 156), and the accuracy of the nodal evaluation of metastasis was 99 % (155 of 156). Suprapyloric lymph node (LN; LN No. 5) and infrapyloric LN (LN No. 6) were detected as SNs in 6 and 14 % of the patients, respectively. We also found two cases with metastasis to LN No. 5 or LN No. 6. DISCUSSION: When performing PPG, the possibility of LN metastasis, especially to LN No. 5 and LN No. 6, cannot be underestimated. SN mapping can play an important role to predict the possibility of metastasis to LN No. 5 and LN No. 6. PMID- 27364501 TI - Increased RhoA Activity Predicts Worse Overall Survival in Patients Undergoing Surgical Resection for Lauren Diffuse-Type Gastric Adenocarcinoma. AB - BACKGROUND: Several studies have reported a high rate of RHOA mutations in the Lauren diffuse-type gastric adenocarcinoma (GA) but not in intestinal-type GA. The aim of this study was to determine if RhoA activity is prognostic for overall survival (OS) in patients with resectable GA. METHODS: Retrospective review was performed on a prospective database of GA patients who underwent potentially curative resection between 2003 and 2012 at a single institution. Tissue microarrays were constructed from surgical specimens and analyzed for phosphorylated RhoA, a marker of inactive RhoA signaling. OS was estimated by the Kaplan-Meier method, and multivariate analysis was performed by Cox proportional hazards regression modeling. RESULTS: One hundred thirty-six patients with diffuse-type GA and 129 patients with intestinal-type GA were examined. Compared to intestinal-type GA, diffuse-type GA tumors were significantly associated with increased tumor size and advanced tumor, node, metastasis (TNM) classification system stage. In patients with diffuse-type GA, high RhoA activity was associated with significantly worse OS when compared to low RhoA activity (5-year OS 52.5 vs. 81.0 %, p = 0.017). This difference in OS was not observed in patients with intestinal-type GA (5-year OS 83.9 vs. 81.6 %, p = 0.766). On multivariate analysis of diffuse-type GA patients, high RhoA activity was an independent negative prognostic factor for OS (hazard ratio 2.38, 95 % confidence interval 1.07-5.28). CONCLUSIONS: Increased RhoA activity is predictive of worse OS in patients with diffuse-type GA who undergo potentially curative surgical resection. Along with findings from genomic studies, these results suggest RhoA may be a novel therapeutic target in diffuse-type GA. PMID- 27364502 TI - Current Practices and Barriers to the Integration of Oncoplastic Breast Surgery: A Canadian Perspective. AB - BACKGROUND: Despite the safety and popularity of oncoplastic surgery, there is limited data examining utilization and barriers associated with its incorporation into practice. This study examines the use of oncoplastic techniques in breast conserving surgery and determines the barriers associated with their implementation. METHODS: A 13-item survey was mailed to all registered general surgeons in Ontario, Canada. The survey assessed surgeon demographics, utilization of specific oncoplastic techniques, and perceived barriers. RESULTS: A total of 234 survey responses were received, representing a response rate of 32.2 % (234 of 725). Of the respondents, 166 surgeons (70.9 %) reported a practice volume of at least 25 % breast surgery. Comparison was made between general surgeons performing oncoplastic breast surgery (N = 79) and those who did not use these techniques (N = 87). Surgeon gender, years in practice, fellowship training, and access to plastic surgery were similar across groups. Both groups rated the importance of breast cosmesis similarly. General surgeons with a practice volume involving >50 % breast surgery were more likely to use oncoplastic techniques (OR 8.82, p < .001) and involve plastic surgeons in breast conserving surgery (OR 2.21, p = .02). For surgeons not performing oncoplastic surgery, a lack of training and access to plastic surgeons were identified as significant barriers. For those using oncoplastic techniques, the absence of specific billing codes was identified as a limiting factor. CONCLUSIONS: Lack of training, access to plastic surgeons, and absence of appropriate reimbursement for these cases are significant barriers to the adoption of oncoplastic techniques. PMID- 27364503 TI - Breast Cancer Clinical Trials: Past Half Century Moving Forward Advancing Patient Outcomes. AB - Clinical trials in breast cancer have contributed immensely to the advancements of modern multimodal breast cancer treatment. Due to improved screening methods and more effective biologic-based tailored systemic therapies, the extent of surgery necessary for local and systemic control of disease is decreasing. Sequential trials for ductal carcinoma in situ (DCIS) have changed the management of this disease and are culminating in randomized active surveillance studies in an effort potentially to prevent overtreatment of low- and intermediate-grade disease. For patients with initial node-positive disease, clipping and marking of the biopsy-proven nodal metastases before the start of neoadjuvant chemotherapy can allow for selective node dissection based on the axillary response. With the current advances in primary systemic therapy, feasibility trials are beginning to investigate the potential of nonoperative therapy for invasive cancers with percutaneously documented pathologic complete response. This article presents a review and update on landmark clinical trials related to DCIS, the extent of axillary surgery in node-positive disease, and the integration of systemic therapy with local therapy. PMID- 27364504 TI - Pediatric and Adolescent Melanoma: A National Cancer Data Base Update. AB - BACKGROUND: Studies suggest that the biology of pediatric and adolescent melanoma differs from that of adult disease. We report the largest series to date examining the natural history of pediatric and adolescent melanoma. We aim to elucidate the natural history of pediatric and adolescent melanoma and to examine the appropriateness of diagnostic and therapeutic modalities developed for adults and that are currently being used in children. METHODS: A retrospective cohort study was conducted of patients with an index diagnosis of cutaneous non metastatic melanoma from 1998 to 2011 using the National Cancer Data Base (NCDB; n = 420,416). Three age-based cohorts were analyzed: 1-10 years (pediatric), 11 20 years (adolescent), and >=21 years (adult). Multivariate analyses were used to identify factors associated with overall survival (OS). RESULTS: Pediatric melanoma patients have longer OS than their adolescent (hazard ratio [HR] 0.50, 95 % CI 0.25-0.98) and adult counterparts (HR 0.11, 95 % CI 0.06-0.21). Adolescents have longer OS than adults. No difference was found in OS in pediatric patients who are node-positive versus node-negative. In pediatric patients, sentinel lymph node biopsy and completion lymph node dissection are not associated with increased OS. In adolescents, nodal positivity is a significant negative prognostic indicator (HR 4.82, 95 % CI 3.38-6.87). CONCLUSIONS: Age based differences in melanoma outcomes warrant different considerations for diagnostic and therapeutic approaches in each group in order to maximize quality of life while minimizing complications and costs. Prospective, multicenter studies should evaluate the role of diagnostic procedures for pediatric patients. PMID- 27364505 TI - The Impact of Neoadjuvant Treatment on Surgical Options and Outcomes. AB - Neoadjuvant systemic therapy (NST) has become a well-established treatment method for patients with breast cancer, not only for those with large tumors, but also for patients with early high-risk cancers. In earlier times, the clinical advantage of NST was seen in improvement of tumor shrinkage for better operability, conversion of mastectomy candidates to breast conservation, and optimization of cosmetic results. Over the decades, therapy regimens were optimized, resulting in significantly higher response rates. Rates for breast conservation and for conversion from mastectomy to breast conservation, especially for patients with advanced breast cancers, rose significantly for patients undergoing NST. A multidisciplinary approach with close and accurate diagnostic assessment of the breast, axillary tumor, or both during NST and individual-response-guided surgery is mandatory. To reduce unnecessary surgery and prevent mastectomies, more conclusive prediction models and minimally invasive methods for selection of patients with pathologic complete remission after NST are needed. Furthermore, prospective studies demonstrate that sentinel node biopsy for patients with initial clinically node-positive axillary nodes converting to clinically node-negative axillary nodes is oncologically safe and offers less morbidity, avoiding complete axillary node dissection. Initial concerns regarding surgical complications and morbidity due to potential immune frailty of patients with NST were not observed. PMID- 27364506 TI - Contralateral Prophylactic Mastectomy for Women with T4 Locally Advanced Breast Cancer. AB - BACKGROUND: The use of contralateral prophylactic mastectomy (CPM) for women with unilateral breast cancer is increasing. The authors were interested in assessing whether this trend extended to patients with T4 disease. METHODS: We identified 92 patients from our prospective breast surgery registry with unilateral clinical T4 M0 disease who underwent mastectomy at our institution from October 2008 to July 2015. Patient, tumor, and treatment variables were compared between patients who did and those who did not undergo CPM, and the reasons patients elected CPM were ascertained. RESULTS: Of the 92 patients, 33 (36 %) underwent a CPM, including 25 of 55 patients (45 %) with inflammatory breast cancer. Immediate breast reconstruction was performed for 11 of the 92 patients (12 %), including 4 CPM patients. Pathology showed benign findings in all 33 CPM cases, including 3 patients with atypical hyperplasia. The primary reason for CPM reported by the patients included fear of occult current or future breast cancer in 12 cases (36 %), symmetry in 11 cases (33 %), avoidance of future chemotherapy in 5 cases (15 %), deleterious BRCA mutation in 2 cases (6 %), contralateral benign breast disease in 2 cases (6 %), and medical oncologist recommendation in 1 cases (3 %). Patients selecting CPM were younger and more likely to have undergone BRCA testing. CONCLUSIONS: A substantial rate of CPM was observed among women undergoing mastectomy for unilateral T4 breast cancer despite the considerable risk of mortality from their index cancer. The reasons for selection of CPM paralleled those reported for patients with early-stage disease. The most common motivation was fear of occult current or future breast cancer and included the desire to avoid further chemotherapy. PMID- 27364508 TI - Influential Forces in Breast Cancer Surgical Decision Making and the Impact on Body Image and Sexual Function. AB - BACKGROUND: Shared decision making with one's partner and body image satisfaction may affect surgical choices of breast cancer patients. This study analyzed whether partner opinion was associated with choice of operation and whether comfort level with one's partner was altered postoperatively. METHODS: A prospective anonymous survey was administered to breast cancer patients who underwent breast surgery between 2000 and 2014. Categorical variables were compared by chi (2) or Fisher's exact test. RESULTS: Women who elected to undergo mastectomy with reconstruction (MR) placed greater emphasis on their own decision making than on input from their partner, surgeon, or others (56.5 vs. 8.3 vs. 23.2 vs. 12, respectively), whereas those who chose lumpectomy (L) placed similar weight on surgeon input and self-input (44.2 vs. 42.7 %). Only 7.5 % of all patients identified their partner as the greatest influence on their surgical choice. Preoperatively, the L group was the most comfortable with their partner seeing their chest (91.9 % L vs. 83.9 % MR vs. 75.9 % mastectomy alone (M); p = 0.01), and postoperatively, the comfort levels for all were remarkably decreased. Furthermore, if a patient was a candidate for L but chose MR, the role her chest played in intimacy dropped more compared with those who chose L (83.8 % L vs. 91.7 % MR; p = 0.3 preoperatively to 65.1 % L vs. 42.9 % MR; p = 0.01 postoperatively). CONCLUSIONS: When making surgical decisions, most patients indicate that they value their own opinion over that of others. Mastectomy, regardless of reconstruction, leads to a significant reduction in comfort with one's partner postoperatively compared with lumpectomy. This information may be helpful in counseling couples at the time of consultation for breast cancer treatment. PMID- 27364507 TI - Early-Stage Breast Cancer in the Octogenarian: Tumor Characteristics, Treatment Choices, and Clinical Outcomes. AB - BACKGROUND: Nodal staging with sentinel node biopsy (SLNB), post-lumpectomy radiotherapy (RT), and endocrine therapy (ET) for estrogen receptor-positive (ER+) tumors is valuable in the treatment of early-stage (stages 1 or 2) breast cancer but used less often for elderly women. METHODS: This retrospective study investigated women referred for surgical evaluation of biopsy-proven primary early-stage invasive breast cancer from January 2001 to December 2010. Clinicopathologic features, treatment course, and outcomes for women ages 80-89 years and 50-59 years were compared. RESULTS: The study identified 178 eligible women ages 80-89 years and 169 women ages 50-59 years. The elderly women more often had grade 1 or 2 disease (p = 0.003) and ER+ tumors (p = 0.007) and less frequently had undergone adjuvant therapies (all p <= 0.001). Lumpectomy was performed more commonly for the elderly (92 vs. 83 %, p = 0.02), and axillary surgery was less commonly performed (46 vs. 96 %; p < 0.001). Fewer elderly women had undergone post-lumpectomy RT (42 vs. 89 %; p < 0.001) and ET for ER+ tumors (72 vs. 95 %; p < 0.001). During the median follow-up period of 56 months for the 80- to 89-year old group and 98 months for the 50- to 59-year-old group, death from breast cancer was similar (4 vs. 5 %; p = 0.5). The two groups respectively experienced 7 versus 6 locoregional recurrences and 11 versus 13 distant recurrences. CONCLUSIONS: The octogenarians had disease survivorship similar to that of the younger women despite less frequent use of adjuvant therapies, likely reflecting lower-risk disease features. Whether increased use of axillary surgery, post-lumpectomy RT, and/or ET for ER+ tumors would further improve outcomes is an important area for further study, but treatment should not be deferred solely on the basis of age. PMID- 27364509 TI - Perioperative Adiponectin Measurement is Useful for Prediction of Postoperative Infection in Patients with Colorectal Cancer. AB - BACKGROUND: Adiponectin (ADN) is a key molecule associated with obesity and metabolic syndrome, and functions as an immunomodulator. We have shown that the ADN ratio (i.e., postoperative ADN/preoperative ADN) can predict infection after gastrectomy in patients with gastric cancer . In the present study, we evaluated whether the ADN ratio could reliably predict the incidence of postoperative infection in patients undergoing colorectal cancer surgery. METHODS: We retrospectively analyzed 131 consecutive patients who underwent colorectal cancer surgery and measured their preoperative and postoperative ADN values. The outcome was postoperative infection, including surgical site and remote infections. The association between the ADN ratio and postoperative infection was assessed using logistic regression models. For the ADN ratio and other significant predictors, we conducted receiver operating characteristics (ROC) analyses. RESULTS: Forty nine patients (37.4 %) experienced postoperative infections. Logistic regression analysis indicated that the ADN ratio was most significantly associated with postoperative infection [odds ratio per one standard deviation (1 SD) decrease 0.36; 95 % confidence interval 0.18-0.71] even after adjustment for diabetes, type of surgery, blood loss, C-reactive protein level, and preoperative ADN level. History of type 2 diabetes mellitus also significantly predicted postoperative infection (odds ratio per 1 SD increase 2.93; 95 % confidence interval 1.03-8.38). When predicting postoperative infection, the area under the ROC curve for the ADN ratio (0.707) was comparable to that for blood loss (0.698; p = 0.975). CONCLUSIONS: ADN ratio is a clinically useful predictor of postoperative infection in patients undergoing colorectal cancer. PMID- 27364510 TI - Neurotrophin Receptor-Interacting Melanoma Antigen-Encoding Gene Homolog is Associated with Malignant Phenotype of Gastric Cancer. AB - BACKGROUND: Identification of novel molecules implicated in the malignancy of gastric cancer (GC) is key to the development of personalized treatments and the improvement of patient outcome. Neurotrophin receptor-interacting melanoma antigen-encoding protein (NRAGE) regulates apoptosis and metastasis via interactions with various genes. This study aimed to evaluate the function and clinical significance of NRAGE in GC. METHODS: The expression of NRAGE and its putative interacting genes apoptosis antagonizing transcription factor (AATF), p75 neurotrophin receptor (p75NTR), and proliferating cell nuclear antigen (PCNA) were determined in GC cell lines using reverse transcription-polymerase chain reaction (RT-PCR). The effect of NRAGE knockdown by small interfering RNA (siRNA) on GC cell behavior also was evaluated. In addition, NRAGE expression was determined in 179 pairs of resected gastric tissues. RESULTS: Expression of NRAGE mRNA positively correlated with that of AATF, and NRAGE knockdown significantly decreased the proliferation, migration, and invasion of GC cells. The mean level of NRAGE mRNA expression was significantly higher in GC tissues than in corresponding adjacent normal tissues. The expression patterns of NRAGE mRNA and protein were closely correlated. A stepwise elevation in NRAGE mRNA expression in GC tissues was observed with increasing Union for International Cancer Control (UICC) stage. High NRAGE expression in GCs was associated with shortened recurrence-free survival and identified as an independent prognostic factor (hazard ratio, 1.83; 95 % CI, 1.12-3.02, p = 0.017). CONCLUSIONS: The results indicate that NRAGE represents a putative oncogene associated with a malignant phenotype of GC. In GC, NRAGE may serve as a predictive biomarker and a target of molecular therapy. PMID- 27364511 TI - FIB-4 Index is a Predictor of Background Liver Fibrosis and Long-Term Outcomes After Curative Resection of Hepatocellular Carcinoma. AB - BACKGROUND: The FIB-4 index is a simple formula for predicting the degree of liver fibrosis. This study aimed to examine the relationship between the preoperative FIB-4 index and liver fibrosis in non-tumor regions of surgical specimens and to investigate whether the FIB-4 index is a useful predictor for long-term outcomes experienced by hepatocellular carcinoma (HCC) patients after curative resection. METHODS: This study retrospectively analyzed 493 HCC patients treated with curative resection. The utility of the FIB-4 index as a predictor of advanced liver fibrosis (F3 or F4) was assessed. The cutoff value for the FIB-4 index was determined using a receiver operating characteristic curve analysis, and the impact of the FIB-4 index on overall and recurrence-free survival after surgery was evaluated. RESULTS: Advanced liver fibrosis was found in 236 patients (47.9 %). The FIB-4 index was significantly higher for the patients with advanced liver fibrosis than for those without this condition (P < 0.001). An FIB-4 index of 2.87 was the optimal cutoff point for predicting advanced liver fibrosis. The multivariate analysis showed the FIB-4 index to be an independent prognostic factor for recurrence-free and overall survival after curative resection only for patients who underwent hepatectomy as initial treatment (hazard ratio, 1.47 and 1.59; 95 % confidence interval, 1.12-1.93 and 1.09-2.32; P = 0.006 and 0.016, respectively). CONCLUSIONS: The study showed the FIB4-index to be a predictor of background liver fibrosis and long-term outcomes for HCC patients who underwent hepatectomy as their initial treatment. PMID- 27364512 TI - Sucrose diffusion in aqueous solution. AB - The diffusion of sugar in aqueous solution is important both in nature and in technological applications, yet measurements of diffusion coefficients at low water content are scarce. We report directly measured sucrose diffusion coefficients in aqueous solution. Our technique utilises a Raman isotope tracer method to monitor the diffusion of non-deuterated and deuterated sucrose across a boundary between the two aqueous solutions. At a water activity of 0.4 (equivalent to 90 wt% sucrose) at room temperature, the diffusion coefficient of sucrose was determined to be approximately four orders of magnitude smaller than that of water in the same material. Using literature viscosity data, we show that, although inappropriate for the prediction of water diffusion, the Stokes Einstein equation works well for predicting sucrose diffusion under the conditions studied. As well as providing information of importance to the fundamental understanding of diffusion in binary solutions, these data have technological, pharmaceutical and medical implications, for example in cryopreservation. Moreover, in the atmosphere, slow organic diffusion may have important implications for aerosol growth, chemistry and evaporation, where processes may be limited by the inability of a molecule to diffuse between the bulk and the surface of a particle. PMID- 27364513 TI - Sensory Processing in Low-Functioning Adults with Autism Spectrum Disorder: Distinct Sensory Profiles and Their Relationships with Behavioral Dysfunction. AB - Sensory processing abnormalities are relatively universal in individuals with autism spectrum disorder, and can be very disabling. Surprisingly, very few studies have investigated these abnormalities in low-functioning adults with autism. The goals of the present study were (a) to characterize distinct profiles of sensory dysfunction, and (b) to understand how sensory dysfunction relates to behavioral disorders in this population. Data were collected for a representative sample of inpatients in autism care centers (N = 148) and a non-clinical control group. Results demonstrated that sensory dysfunction (a) is highly prevalent in low-functioning adults with ASD and differentiates at least four sub-profiles of patients, and (b) predicts specific patterns of behavioral disorders. Implications for care are discussed. PMID- 27364514 TI - Operationalisation of the European Protocol for Autism Prevalence (EPAP) for Autism Spectrum Disorder Prevalence Measurement in Ireland. AB - The European Autism Information System project highlighted the lack of systematic and reliable data relating to the prevalence of autism spectrum disorders in Europe. A protocol for the study of ASD prevalence at European level was developed to facilitate a common format for screening and diagnosing children across the EU. This is the first study to operationalise and screen national school children for ASDs using this protocol. National school children 6-11 years (N = 7951) were screened males 54 % (N = 4268) females 46 % (N = 3683). Screening children for ASD implementing the EAIS protocol using the Social Communication Questionnaire (Rutter et al. in Social Communication Questionnaire (SCQ). Western Psychological Services, Los Angeles, ) as a first level screening instrument in a non-clinical setting of Irish national schools was demonstrated. PMID- 27364515 TI - Neurodevelopmental Disorders (ASD and ADHD): DSM-5, ICD-10, and ICD-11. AB - Neurodevelopmental disorders, specifically autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have undergone considerable diagnostic evolution in the past decade. In the United States, the current system in place is the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), whereas worldwide, the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) serves as a general medical system. This review will examine the differences in neurodevelopmental disorders between these two systems. First, we will review the important revisions made from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) to the DSM-5, with respect to ASD and ADHD. Next, we will cover the similarities and differences between ASD and ADHD classification in the DSM-5 and the ICD-10, and how these differences may have an effect on neurodevelopmental disorder diagnostics and classification. By examining the changes made for the DSM-5 in 2013, and critiquing the current ICD-10 system, we can help to anticipate and advise on the upcoming ICD-11, due to come online in 2017. Overall, this review serves to highlight the importance of progress towards complementary diagnostic classification systems, keeping in mind the difference in tradition and purpose of the DSM and the ICD, and that these systems are dynamic and changing as more is learned about neurodevelopmental disorders and their underlying etiology. Finally this review will discuss alternative diagnostic approaches, such as the Research Domain Criteria (RDoC) initiative, which links symptom domains to underlying biological and neurological mechanisms. The incorporation of new diagnostic directions could have a great effect on treatment development and insurance coverage for neurodevelopmental disorders worldwide. PMID- 27364516 TI - Identification with Multiple Groups in Multiethnic Middle Schools: What Predicts Social Ingroup Overlap? AB - Self-definition becomes a central task during early adolescence, as youth identify with multiple social groups. Focusing on ethnic identification and identification with other salient social ingroups (e.g., those based on extracurricular activities), we examined predictors of perceived ingroup membership overlap among ethnically diverse adolescents (n = 1264; M age = 12.51; 53 % female). Social ingroup overlap remained relatively stable, but decreased, across the seventh to eighth grade. The number of cross-ethnic classmates in seventh grade predicted lower overlap in the eighth grade, and cross-ethnic friendships by eighth grade mediated this association. Findings underscore the opportunities provided by multiethnic middle schools for youth to connect and befriend one another across ethnic lines, as well as to foster divergent social identities that are associated with positive intergroup attitudes. PMID- 27364517 TI - Impact of Formulation on the Pharmacokinetic Profile of Dutasteride. PMID- 27364518 TI - Effects of hydroxyethyl starch 6 % (130/0.4) on blood loss during cesarean delivery: a propensity-matched analysis. AB - BACKGROUND: Hydroxyethyl starch is commonly used in the obstetric patient population to prevent hypotension during cesarean delivery. Evidence suggests hetastarch is associated with a dysfunction in coagulation cascade. We hypothesized that hetastarch use to prevent spinal hypotension during cesarean delivery would be associated with an increase in blood loss when compared to crystalloid use. METHODS: We performed a retrospective review of patients who underwent elective cesarean delivery under spinal anesthesia at the University of Virginia between 2011 and 2014. Data from 819 patients was used. Blood loss was the primary outcome. Propensity score-matching was used to match patients who received hetastarch (treatment group) with those who did not receive hetastarch (control group). RESULTS: Genetic matching resulted in 196 patients in the hetastarch group and 182 patients in the control group. There was no difference in estimated blood loss (p = 0.068), calculated blood loss (p = 0.720), total intraoperative fluid intake (p = 0.289), urine output (p = 0.421), Apgar 1 min (p = 0.830), Apgar 5 min (p = 0.138), phenylephrine consumption (p = 0.742), postoperative day 1 (POD1) hematocrit (p = 0.070) and POD1 platelets (p = 0.233). However, there was a statistically significant difference (but clinically irrelevant) in hematocrit difference between the day of admission and POD1 (mean difference 0.47, p = 0.024), and ephedrine consumption (mean difference 2 mg, p = 0.017) in favor of the control group. CONCLUSIONS: Our study did not find an association between increased perioperative blood loss and hetastarch use in patients presenting for elective cesarean delivery. PMID- 27364519 TI - Distinguishing ischaemic optic neuropathy from optic neuritis by ganglion cell analysis. AB - PURPOSE: To determine whether a pattern of altitudinal ganglion cell loss, as detected and measured by optical coherence tomography (OCT), can be used to distinguish non-arteritic ischaemic optic neuropathy (NAION) from optic neuritis (ON) during the acute phase, and whether the rate or severity of ganglion cell loss differs between the two diseases. METHODS: We performed a retrospective, case-control study of 44 patients (50 eyes) with ON or NAION and 44 age-matched controls. Non-arteritic ischaemic optic neuropathy and ON patients had OCT at presentation and four consecutive follow-up visits. Controls had OCT at one point in time. The ganglion cell complex (GCC) was evaluated in the macula, and the retinal nerve fibre layer (RNFL) was evaluated in the peripapillary region. Ganglion cell complex thickness, RNFL thickness and GCC mean superior and inferior hemispheric difference were compared between NAION and ON patients at each time-point using unpaired t-tests and between disease and control subjects at first measurement using paired t-tests. RESULTS: Mean time from onset of symptoms to initial presentation was 10.7 +/- 6.6 days in NAION and 11.7 +/- 8.6 days in ON (p = 0.67). There was a significantly greater vertical hemispheric difference in GCC thickness in NAION patients than ON patients at all time-points (5.5-10.7 MUm versus 3.1-3.6 MUm, p = 0.01-0.049). Mean GCC thickness was significantly decreased at less than 2 weeks after onset in NAION compared to age matched controls (72.1 MUm versus 82.1 MUm, p < 0.001), as well as in ON compared to age-matched controls (74.3 MUm versus 84.5 MUm, p < 0.001). Progression and severity of GCC and RNFL loss did not differ significantly between NAION and ON. CONCLUSION: A quantitative comparison of mean superior and inferior hemispheric GCC thickness with OCT may be used to distinguish NAION from ON. PMID- 27364520 TI - The rationale and the role of lymph node dissection in renal cell carcinoma. AB - PURPOSE: Although the role of lymph node dissection (LND) is well defined in many urological settings, uncertainty regarding need for LND still exists for patients with renal cell carcinoma (RCC). The aim of the current review is to highlight the rationale for performing or omitting LND at the time of renal surgery. METHODS: Data were identified through a search of PubMed and Web of Science, including studies published in the last 20 years in core clinical journals. The review is based on evidence synthesis from a peer-review process of the two authors after a structured data search. RESULTS: Neither imaging, nor predictive tools or molecular/genetic markers accurately identify which patients may warrant a LND. In patients with clinical T1abN0 and absence of unfavorable clinical and pathological characteristics, LND does not appear to offer benefit in terms of staging and cancer control. Conversely, LND can be considered in selected cases (larger tumors, locally advanced diseases or when unfavorable pathological characteristics are likely, as high Fuhrman grade, sarcomatoid features or tumor necrosis) due to the non-negligible risk of associated nodal metastases and possible benefit in terms of cancer control. CONCLUSIONS: Although LND does not provide any benefit in the majority of RCC cases (mainly T1abN0M0 cases), it remains an important consideration in intermediate-/high-risk patients for staging purposes, given an increased risk of LNI, and for potential benefit in terms of cancer control. Additional data are urgently needed to improve the accuracy of nodal staging tools and to evaluate the potential role of salvage LND. PMID- 27364521 TI - Feasibility of conductivity imaging using subject eddy currents induced by switching of MRI gradients. AB - PURPOSE: To investigate the feasibility of low-frequency conductivity imaging based on measuring the magnetic field due to subject eddy currents induced by switching of MRI z-gradients. METHODS: We developed a simulation model for calculating subject eddy currents and the magnetic fields they generate (subject eddy fields). The inverse problem of obtaining conductivity distribution from subject eddy fields was formulated as a convection-reaction partial differential equation. For measuring subject eddy fields, a modified spin-echo pulse sequence was used to determine the contribution of subject eddy fields to MR phase images. RESULTS: In the simulations, successful conductivity reconstructions were obtained by solving the derived convection-reaction equation, suggesting that the proposed reconstruction algorithm performs well under ideal conditions. However, the level of the calculated phase due to the subject eddy field in a representative object indicates that this phase is below the noise level and cannot be measured with an uncertainty sufficiently low for accurate conductivity reconstruction. Furthermore, some artifacts other than random noise were observed in the measured phases, which are discussed in relation to the effects of system imperfections during readout. CONCLUSION: Low-frequency conductivity imaging does not seem feasible using basic pulse sequences such as spin-echo on a clinical MRI scanner. Magn Reson Med 77:1926-1937, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27364522 TI - In vivo assessment of behavioral recovery and circulatory exchange in the peritoneal parabiosis model. AB - The sharing of circulation between two animals using a surgical procedure known as parabiosis has created a wealth of information towards our understanding of physiology, most recently in the neuroscience arena. The systemic milieu is a complex reservoir of tissues, immune cells, and circulating molecules that is surprisingly not well understood in terms of its communication across organ systems. While the model has been used to probe complex physiological questions for many years, critical parameters of recovery and exchange kinetics remain incompletely characterized, limiting the ability to design experiments and interpret results for complex questions. Here we provide evidence that mice joined by parabiosis gradually recover much physiology relevant to the study of brain function. Specifically, we describe the timecourse for a variety of recovery parameters, including those for general health and metabolism, motor coordination, activity, and sleep behavior. Finally, we describe the kinetics of chimerism for several lymphocyte populations as well as the uptake of small molecules into the brains of mice following parabiosis. Our characterization provides an important resource to those attempting to understand the complex interplay between the immune system and the brain as well as other organ systems. PMID- 27364523 TI - Histological characterization of orphan transporter MCT14 (SLC16A14) shows abundant expression in mouse CNS and kidney. AB - BACKGROUND: MCT14 (SLC16A14) is an orphan member of the monocarboxylate transporter (MCT) family, also known as the SLC16 family of secondary active transmembrane transporters. Available expression data for this transporter is limited, and in this paper we aim to characterize MCT14 with respect to tissue distribution and cellular localization in mouse brain. RESULTS: Using qPCR, we found that Slc16a14 mRNA was highly abundant in mouse kidney and moderately in central nervous system, testis, uterus and liver. Using immunohistochemistry and in situ hybridization, we determined that MCT14 was highly expressed in excitatory and inhibitory neurons as well as epithelial cells in the mouse brain. The expression was exclusively localized to the soma of neurons. Furthermore, we showed with our phylogenetic analysis that MCT14 most closely relate to the aromatic amino acid- and thyroid-hormone transporters MCT8 (SLC16A2) and MCT10 (SLC16A10), in addition to the carnitine transporter MCT9 (SLC16A9). CONCLUSIONS: We provide here the first histological mapping of MCT14 in the brain and our data are consistent with the hypothesis that MCT14 is a neuronal aromatic-amino-acid transporter. PMID- 27364525 TI - Media coverage of statins may have led to 2000 cardiovascular events. PMID- 27364524 TI - Phosphatidic Acid Sequesters Sec18p from cis-SNARE Complexes to Inhibit Priming. AB - Yeast vacuole fusion requires the activation of cis-SNARE complexes through priming carried out by Sec18p/N-ethylmaleimide sensitive factor and Sec17p/alpha SNAP. The association of Sec18p with vacuolar cis-SNAREs is regulated in part by phosphatidic acid (PA) phosphatase production of diacylglycerol (DAG). Inhibition of PA phosphatase activity blocks the transfer of membrane-associated Sec18p to SNAREs. Thus, we hypothesized that Sec18p associates with PA-rich membrane microdomains before transferring to cis-SNARE complexes upon PA phosphatase activity. Here, we examined the direct binding of Sec18p to liposomes containing PA or DAG. We found that Sec18p preferentially bound to liposomes containing PA compared with those containing DAG by approximately fivefold. Additionally, using a specific PA-binding domain blocked Sec18p binding to PA-liposomes and displaced endogenous Sec18p from isolated vacuoles. Moreover, the direct addition of excess PA blocked the priming activity of isolated vacuoles in a manner similar to chemically inhibiting PA phosphatase activity. These data suggest that the conversion of PA to DAG facilitates the recruitment of Sec18p to cis-SNAREs. Purified vacuoles from yeast lacking the PA phosphatase Pah1p showed reduced Sec18p association with cis-SNAREs and complementation with plasmid-encoded PAH1 or recombinant Pah1p restored the interaction. Taken together, this demonstrates that regulating PA concentrations by Pah1p activity controls SNARE priming by Sec18p. PMID- 27364526 TI - Letter by Du et al Regarding Article, "Neutrophil-to-Lymphocyte Ratio Predicts the Outcome of Acute Intracerebral Hemorrhage". PMID- 27364527 TI - Response by Lattanzi and Silvestrini to Letter Regarding Article, "Neutrophil-to Lymphocyte Ratio Predicts the Outcome of Acute Intracerebral Hemorrhage". PMID- 27364528 TI - Safety of Computed Tomographic Angiography in the Evaluation of Patients With Acute Stroke: A Single-Center Experience. AB - BACKGROUND AND PURPOSE: Noncontrasted head computed tomography (NCHCT) has long been the standard of care for acute stroke imaging. New guidelines recommending advanced vascular imaging to identify eligible patients for endovascular therapy have renewed safety concerns on the use of contrast in the emergent setting without laboratory confirmation of renal function. METHODS: We compared computed tomographic angiography (CTA) versus NCHCT alone during acute stroke evaluation with focus on renal safety and timeliness of therapy delivery. We reviewed data on all emergency department patients for whom the Acute Stroke Intervention Team was activated between December 2013 and September 2014. Primary outcomes included acute kidney injury and change in serum creatinine from presentation to 24 to 48 hours (Delta serum creatinine [Cr]). We assessed therapy delay using door-to-CT and door-to-needle times. RESULTS: Of 289 patients requiring Acute Stroke Intervention Team activation, 157 received CTA and 132 NCHCT only. There was no difference between groups in mean Cr at 24 to 48 hours (1.06 CTA; 1.40 NCHCT; P=0.059), DeltaCr (-0.07 CTA, -0.11 NCHCT, P=0.489), or rates of acute kidney injury (5 CTA, 7 NCHCT, P=0.422). There was no significant difference in mean intravenous tissue plasminogen activator treatment times (68.11 minutes CTA, 81.36 minutes NCHCT; P=0.577). In the 157 patients who underwent CTA, 16 (10.2%) vascular anomalies and 55 (35.0%) high-grade stenoses or occlusions were identified. CONCLUSIONS: CTA acquisition during acute stroke evaluation was safe with regards to renal function and did not delay appropriate therapy delivery. Acute CTA acquisition offers additional clinical value in rapid identification of vascular abnormalities. PMID- 27364529 TI - Letter by Guo et al Regarding Article, "Lymphocytopenia Is an Independent Predictor of Unfavorable Functional Outcome in Spontaneous Intracerebral Hemorrhage". PMID- 27364530 TI - Repeated Intravenous Thrombolysis for Early Recurrent Stroke: Challenging the Exclusion Criterion. AB - BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) within 4.5 hours from symptom onset improves functional outcome in patients with acute ischemic stroke. Its use in patients with previous stroke within the preceding 3 months is contraindicated because of the assumed higher risk of intracranial hemorrhage. In addition, tissue-type plasminogen activator may itself promote neurotoxicity and blood-brain barrier disruption. However, safety and effectiveness of repeated IVT is essentially unknown in patients with early (<3 months) recurrent stroke (ERS), because they were excluded from thrombolysis trials. This article reports the largest case series of repeated IVT in ERS. METHODS: We reviewed databases of prospectively collected patient data of 8 European stroke centers for the presence of patients with ERS, who received IVT for both the index stroke and ERS. Demographics, clinical and radiological data, bleeding complications, and functional outcome were analyzed. RESULTS: We identified 19 subjects with repeated IVT in ERS. Mean age was 68+/-12 years, and 37% of them were female. Median interthrombolysis interval was 30 days (interquartile range, 13-50). Functional independence (modified Rankin scale score <=2) was achieved in 79% of patients after the first and in 47.4% after repeated IV tissue-type plasminogen activator, respectively. There was no symptomatic intracranial hemorrhage. Median final infarct volume after the first IVT was 1.5 cm(3) (interquartile range, 0.5 3.1). CONCLUSIONS: Patients with small infarct volumes and robust clinical improvement might be considered for repeated IVT within 3 months. Studies following strict protocols and larger registries incorporating these patients might serve to identify selection criteria for the safe use of repeated IVT in ERS. PMID- 27364531 TI - Field Assessment Stroke Triage for Emergency Destination: A Simple and Accurate Prehospital Scale to Detect Large Vessel Occlusion Strokes. AB - BACKGROUND AND PURPOSE: Patients with large vessel occlusion strokes (LVOS) may be better served by direct transfer to endovascular capable centers avoiding hazardous delays between primary and comprehensive stroke centers. However, accurate stroke field triage remains challenging. We aimed to develop a simple field scale to identify LVOS. METHODS: The Field Assessment Stroke Triage for Emergency Destination (FAST-ED) scale was based on items of the National Institutes of Health Stroke Scale (NIHSS) with higher predictive value for LVOS and tested in the Screening Technology and Outcomes Project in Stroke (STOPStroke) cohort, in which patients underwent computed tomographic angiography within the first 24 hours of stroke onset. LVOS were defined by total occlusions involving the intracranial internal carotid artery, middle cerebral artery-M1, middle cerebral artery-2, or basilar arteries. Patients with partial, bihemispheric, and anterior+posterior circulation occlusions were excluded. Receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and negative predictive value of FAST-ED were compared with the NIHSS, Rapid Arterial Occlusion Evaluation (RACE) scale, and Cincinnati Prehospital Stroke Severity (CPSS) scale. RESULTS: LVO was detected in 240 of the 727 qualifying patients (33%). FAST-ED had comparable accuracy to predict LVO to the NIHSS and higher accuracy than RACE and CPSS (area under the receiver operating characteristic curve: FAST-ED=0.81 as reference; NIHSS=0.80, P=0.28; RACE=0.77, P=0.02; and CPSS=0.75, P=0.002). A FAST-ED >=4 had sensitivity of 0.60, specificity of 0.89, positive predictive value of 0.72, and negative predictive value of 0.82 versus RACE >=5 of 0.55, 0.87, 0.68, and 0.79, and CPSS >=2 of 0.56, 0.85, 0.65, and 0.78, respectively. CONCLUSIONS: FAST-ED is a simple scale that if successfully validated in the field, it may be used by medical emergency professionals to identify LVOS in the prehospital setting enabling rapid triage of patients. PMID- 27364532 TI - How Patient Demographics, Imaging, and Beliefs Influence Tissue-Type Plasminogen Activator Use: A Survey of North American Neurologists. AB - BACKGROUND AND PURPOSE: Understanding physician decision making is increasingly recognized as an important topic of study, especially in stroke care. We sought to characterize the process of acute stroke decision making among neurologists in the United States and Canada from clinical and epistemological perspectives. METHODS: Using a factorial design online survey, respondents were presented with clinical data to mimic an acute stroke encounter. The history, examination, computed tomographic (CT) scan, CT angiogram, and CT perfusion were presented in sequence, and respondents rated their diagnostic confidence and likelihood of treatment with tissue-type plasminogen activator after each element. Patient age, race, sex, and CT perfusion imaging results were randomized, whereas the rest of the clinical presentation was held constant. RESULTS: We collected 715 responses, of which 473 (66%) were complete. Diagnostic certainty and likelihood of treatment with tissue-type plasminogen activator rose incrementally as additional clinical data were provided. Diagnostic certainty and treatment likelihood were strongly influenced by the clinical history and the CT scan. Other factors such as physicians' personal beliefs or biases were not influential. Respondents' accuracy in interpreting CT angiographic and CT perfusion images was variable and generally low. CONCLUSIONS: Diagnostic certainty and likelihood of treatment with tissue-type plasminogen activator increase with additional clinical data, with the history being the most important factor for diagnostic and treatment decisions. Respondents had difficulty in interpreting the results of CT perfusion scans although they had little impact on treatment decisions. We did not identify treatment bias based on patient age, race, or sex. PMID- 27364534 TI - Trends in nursing ethics research: Mapping the literature production. AB - BACKGROUND: There have been a number of debates in the field of nursing ethics. Researchers have focused on various aspects of nursing ethics, such as professional ethics, professional, nursing and ethical values. Within this research, a variety of literature reviews have been conducted, but to the best of our knowledge, bibliometric mapping has not yet been used. OBJECTIVE: This article aims to analyse the production of literature within nursing ethics research. RESEARCH DESIGN: In order to examine publishing patterns, we focused on publishing dynamics, prolific research entities and the most-cited articles. We additionally visualised the content of the literature using a novel mixed-method approach, combining bibliometric analysis and mapping with thematic analysis. Ethical considerations: In our study, ethical review was not required. FINDINGS: A total of 1416 information sources were found in the Scopus database. Overall, literature production has increased; however, in recent years, the quantity of published material has begun to decrease. The most prolific countries are the United States, the United Kingdom and Canada, and the most prolific source titles are Nursing Ethics, Journal of Advanced Nursing and Nursing Times. Lately, research in the field of nursing ethics has been focused more on life care (providing for the basic needs of older residents), moral distress and community nursing. DISCUSSION: The dynamics of research literature production showed an exponential rise in the number of published information sources - a rise which started in the period between 1974 and 1998. Since that period, the trend has stabilised, which might indicate that nursing ethics research is starting a transition to a mature phase. CONCLUSION: The innovative use of bibliometric analysis and mapping, together with thematic analysis, is a useful tool for analysis of research production in the field of nursing ethics. The results presented can be an excellent starting point for literature reviews and more exhaustive data, information and knowledge seeking. PMID- 27364533 TI - Transcriptome-wide based identification of miRs in congenital anomalies of the kidney and urinary tract (CAKUT) in children: the significant upregulation of tissue miR-144 expression. AB - BACKGROUND: The genetic cause of most congenital anomalies of the kidney and urinary tract (CAKUT) cases remains unknown, therefore the novel approaches in searching for the common disease denominators are required. miRs regulate gene expression in humans and therefore have potentially therapeutic and biomarker properties. No studies thus far have attempted to explore the miRs in human CAKUT. We applied a new strategy to identify most specific miRs associated with CAKUT, in pediatric patients. METHODS: Data from the whole genome expression, gathered from ureter tissue samples of 19 patients and 7 controls, were used for the bioinformatic prediction of miRs activity in CAKUT. We integrated microarray gene expression data and miR target predictions from multiple prediction algorithms using Co-inertia analysis (CIA) in conjunction with correspondence analysis and between group analysis, to produce a ranked list of miRs associated with CAKUT. The CIA included five different sequence based miR target prediction algorithms and the Co-expression Meta-analysis of miR Targets. For the experimental validation of expression of miRs identified by the CIA we used tissue from 36 CAKUT patients and 9 controls. The results of gene ontology (GO) analysis on co-expressed targets of miRs associated with CAKUT were used for the selection of putative biological processes relevant to CAKUT. RESULTS: We identified 7 miRs with a potential role in CAKUT. The top ranked miRs from miRCos communities 4, 1 and 7 were chosen for experimental validation of expression in CAKUT tissue. The 5.7 fold increase of hsa-miR-144 expression in human tissue from CAKUT patients compared to controls (p = 0.005) was observed. From the GO we selected 7 biological processes that could contribute to CAKUT, which genes are potentially influenced by hsa-miR-144. The hsa-miR-200a, hsa-miR-183 and hsa-miR 375 weren't differentially expressed in CAKUT. CONCLUSIONS: This study shows that integrative approach applied here was useful in identification of the miRs associated with CAKUT. The hsa-miR-144, first time identified in CAKUT, could be connected with biological processes crucial for normal development of kidney and urinary tract. Further functional analysis must follow to reveal the impact of hsa-miR-144 on CAKUT occurrence. PMID- 27364535 TI - Threats to nurses' dignity and intent to leave the profession. AB - BACKGROUND: It is essential to pay attention to and respect the dignity of nurses to maintain them in their profession while they deliver skilled nursing care. Little is known, however, about how a sense of dignity influences the practitioner. OBJECTIVES: The purpose of this study is to describe nurses' experiences of threats to their dignity occurring within clinical settings, which generates an intention to leave clinical practice. RESEARCH DESIGN AND METHOD: The study was performed using qualitative content analysis. The participants were 21 clinical nurses with work experience who were employed across a range of clinical posts. Data obtained from the semi-structured interviews were analyzed and interpreted using a content analysis approach. Ethical considerations: The study was approved by the Ethics Committee of Tabriz University of Medical Sciences and was guided by the ethical principles of voluntary enrolment, anonymity, privacy, and confidentiality. FINDINGS: Within data analysis, three main themes and nine categories were extracted as follows: (1) lack of professional pride (physician's dominance, intangible nature of nursing, and negative attitude toward clinical nurses); (2) oppressive work environment (high workload, disrespect, discrimination, and lack of support); and (3) suppression of progressivism (lack of appreciation and attention to meritocracy). DISCUSSION: Almost all of the participants have experienced some degree of disrespect and violation of dignity. In general, attempts made by the participants to show their objection to the threats and to support and protect their dignity have not been effective and in fact made them more inclined to leave the clinical work. CONCLUSION: According to the views of nurses themselves, identification of the factors threatening nurses' dignity can be one of the appropriate solutions for the broader and deeper investigation of this phenomenon and can help promote and support nurses' dignity and their retention within the profession. PMID- 27364536 TI - Moral sensitivity, moral distress, and moral courage among baccalaureate Filipino nursing students. AB - BACKGROUND: Moral distress, moral sensitivity, and moral courage among healthcare professionals have been explored considerably in recent years. However, there is a paucity of studies exploring these topics among baccalaureate nursing students. AIM/OBJECTIVE: The purpose of this study was to explore the relationship between and among moral distress, moral sensitivity, and moral courage of undergraduate baccalaureate nursing students. RESEARCH DESIGN: The research employed a descriptive-correlational design to explore the relationships between and among moral distress, moral sensitivity, and moral courage of undergraduate nursing students. Participants and research context: A total of 293 baccalaureate Filipino nursing students who have been exposed to various clinical areas participated in the study. Ethical considerations: Institutional review board approval was sought prior to the conduct of the study. Self-determination was assured and anonymity and confidentiality were guaranteed to all participants. FINDINGS: Results indicate that a majority of the nursing students in the clinical areas encounter morally distressing situations that compromise quality patient care. However, despite the fact that they want to do what is in the best interest of their patients, their perception of being the inexperienced among the healthcare team drives the majority of them to ignore morally distressing situations to avoid conflict and confrontation. Another interesting finding is that 79.20% of the respondents hardly consider quitting the nursing profession even if they frequently encounter morally distressing situations. Analysis also shows associations between moral distress intensity and frequency ( r = 0.13, p < 0.05) and moral distress intensity and moral sensitivity ( r = 0.25, p < 0.05). The dimensions of moral courage are also related to both moral distress and moral sensitivity. CONCLUSION: Results of the study imply that moral distress is a reality among all healthcare professionals including nursing students and requires more consideration by nurse educators. PMID- 27364537 TI - Why high-risk, non-expected-utility-maximising gambles can be rational and beneficial: the case of HIV cure studies. AB - Some early phase clinical studies of candidate HIV cure and remission interventions appear to have adverse medical risk-benefit ratios for participants. Why, then, do people participate? And is it ethically permissible to allow them to participate? Recent work in decision theory sheds light on both of these questions, by casting doubt on the idea that rational individuals prefer choices that maximise expected utility, and therefore by casting doubt on the idea that researchers have an ethical obligation not to enrol participants in studies with high risk-benefit ratios. This work supports the view that researchers should instead defer to the considered preferences of the participants themselves. This essay briefly explains this recent work, and then explores its application to these two questions in more detail. PMID- 27364538 TI - Analysis of propionate-degrading consortia from agricultural biogas plants. AB - In order to investigate the propionate-degrading community of agricultural biogas plants, four propionate-degrading consortia (Ap1a, N12, G12, and Wp2a) were established from different biogas plants which were fed with renewable resources. The consortia were cultivated in a batch for a period of 2-4 years and then analyzed in an 8-week batch experiment for microbial succession during propionate degradation. Community shifts showed considerable propagation of Syntrophobacter sulfatireducens, Cryptanaerobacter sp./Pelotomaculum sp., and "Candidatus Cloacamonas sp." in the course of decreasing propionate concentration. Methanogenic species belonged mainly to the genera Methanosarcina, Methanosaeta, and Methanoculleus. Due to the prevalent presence of the syntrophic acetate oxidizing species Tepidanaerobacter acetatoxydans and potentially autotrophic homoacetogenic bacteria (Moorella sp., Thermacetogenium sp.), a theoretical involvement of syntrophic acetate oxidation and autotrophic homoacetogenesis in stable and efficient propionate degradation was indicated. Considering theoretical Gibbs free energy values at different hydrogen partial pressures, it is noticeable that syntrophic acetate oxidation and autotrophic homoacetogenesis have the potential to counterbalance adverse hydrogen partial pressure fluctuations, stabilizing most probably continuous and stable propionate degradation. PMID- 27364539 TI - Hybrid dynamics in a species group of swallowtail butterflies. AB - Hybrid zones provide unique natural laboratories for studying mechanisms of evolution. But identification and classification of hybrid individuals (F1, F2, backcross, etc.) can be complicated by real population changes over time as well as by use of different marker types, both of which challenge documentation of hybrid dynamics. Here, we use multiple genetic markers (mitochondrial DNA, microsatellites and genomewide single nucleotide polymorphisms) to re-examine population structure in a hybrid zone between two species of swallowtail butterflies in western Canada, Papilio machaon and P. zelicaon. Our aim was to test whether their hybrid dynamics remain the same as found 30 years ago using morphology and allozymes, and we compared different genetic data sets as well as alternative hybrid identification and classification methods. Overall, we found high differentiation between the two parental species, corroborating previous research from the 1980s. We identified fewer hybrid individuals in the main zone of hybridization in recent years, but this finding depended on the genetic markers considered. Comparison of methods with simulated data sets generated from our data showed that single nucleotide polymorphisms were more powerful than microsatellites for both hybrid identification and classification. Moreover, substantial variation among comparisons underlined the value of multiple markers and methods for documenting evolutionarily dynamic systems. PMID- 27364540 TI - Emotional and Sexual Correlates of Child Sexual Abuse as a Function of Self Definition Status. AB - Among individuals defined as having been sexually abused based on legal criteria, some will self-report having been abused and some will not. Yet, the empirical correlates of self-definition status are not well studied. Different definitions of abuse may lead to varying prevalence rates and contradictory findings regarding psychological outcomes. The present study examined whether, among legally defined sexual abuse survivors, identifying oneself as having experienced childhood sexual abuse (CSA) was associated with more severe abuse, negative emotional reactions toward the abuse, and current sexual reactions. A convenience sample of 1,021 French-speaking Canadians completed self-report questionnaires online. The prevalence of legally defined CSA was 21.3% in women and 19.6% in men, as compared to 7.1% in women and 3.8% in men for self-defined CSA. Among legally defined sexual abuse survivors, those who identified themselves as CSA survivors had been abused more frequently, were more likely to report a male aggressor, and more often described abuse by a parental figure than those who did not self-identify as abused. Further, self-defined CSA was associated with more negative postabuse reactions and sexual avoidance, whereas those not identifying as sexually abused were more likely to report sexual compulsion. PMID- 27364541 TI - 2016 ACC/AHA Clinical Performance and Quality Measures for Adults With Atrial Fibrillation or Atrial Flutter: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. PMID- 27364542 TI - Prevalence of hypothyroidism and thyroid nodule in chronic hemodialysis Iranian patients. AB - INTRODUCTION: End stage renal disease (ESRD) reasons several changes in the function of thyroid gland as; lower levels of thyroid hormones, altered hormone metabolism, and increased iodine storage. The aim of this study was to evaluate the prevalence of nodular goiter and hypothyroidism in hemodialysis (HD) patients compared with normal population. METHODS: This cross-sectional study was conducted among HD patients and healthy people as the control group for thyroid function evaluation. Thyroid gland was evaluated by physical examination and ultrasonography. Blood level of FT3, FT4, TSH, TPO Ab, and urinary iodine excretion were checked in both groups. Data were analyzed using SPSS-17 and P value less than 0.05 was considered as the significance level. FINDINGS: Eighty six HD patients (57.2 +/- 17.2 mean age, 48 men) and 86 healthy people (56.6 +/- 16.8 mean age, 48 men) were enrolled in this study. Goiter was confirmed by physical examination in 29.0% of the HD patients and 12.8% of the control group (P = 0.04). Nodular goiter that was shown by ultrasonography was found in 27.9% and 3.5% of the HD and control groups, respectively (P = 0.01). HD patients had a higher frequency of reduced FT3 (40.9% vs. 4.6%, P < 0.01) and increased TSH (18.6% vs. 8.1%, P < 0.03(. TPO Ab was positive in 15.1% of the HD and 11.6% of the control groups (P = 0.14). DISCUSSION: The high incidence of nodular goiter and hypothyroidism in ESRD patients shows that screening for thyroid dysfunction and goiter, using appropriate laboratory tests, should be considered in evaluations of ESRD patients. PMID- 27364543 TI - A model for the interaction of the G3-subdomain of Geobacillus stearothermophilus IF2 with the 30S ribosomal subunit. AB - Bacterial translation initiation factor IF2 complexed with GTP binds to the 30S ribosomal subunit, promotes ribosomal binding of fMet-tRNA, and favors the joining of the small and large ribosomal subunits yielding a 70S initiation complex ready to enter the translation elongation phase. Within the IF2 molecule subdomain G3, which is believed to play an important role in the IF2-30S interaction, is positioned between the GTP-binding G2 and the fMet-tRNA binding C terminal subdomains. In this study the solution structure of subdomain G3 of Geobacillus stearothermophilus IF2 has been elucidated. G3 forms a core structure consisting of two beta-sheets with each four anti-parallel strands, followed by a C-terminal alpha-helix. In line with its role as linker between G3 and subdomain C1, this helix has no well-defined orientation but is endowed with a dynamic nature. The structure of the G3 core is that of a typical OB-fold module, similar to that of the corresponding subdomain of Thermus thermophilus IF2, and to that of other known RNA-binding modules such as IF2-C2, IF1 and subdomains II of elongation factors EF-Tu and EF-G. Structural comparisons have resulted in a model that describes the interaction between IF2-G3 and the 30S ribosomal subunit. PMID- 27364544 TI - Plasma miRNA expression profile in the diagnosis of late-onset hypogonadism. PMID- 27364546 TI - Early Maternal Employment and Children's Academic and Behavioral Skills in Australia and the United Kingdom. AB - This study assessed the links between early maternal employment and children's later academic and behavioral skills in Australia and the United Kingdom. Using representative samples of children born in each country from 2000 to 2004 (Australia N = 5,093, U.K. N = 18,497), OLS regression models weighted with propensity scores assessed links between maternal employment in the 2 years after childbearing and children's skills in first grade. There were neutral associations between maternal employment and children's first-grade skills in both countries. However, there was a slight indication that more time away from parenting was negatively linked to children's behavioral functioning in Australia and employment begun between 9 and 24 months was positively linked to cognitive skills for U.K. children of low-wage mothers. PMID- 27364545 TI - Steroid hormone receptors and prostate cancer: role of structural dynamics in therapeutic targeting. AB - Steroid hormone receptors (SHRs) act in cell type- and gene-specific manner through interactions with coregulatory proteins to regulate numerous physiological and pathological processes at the level of gene regulation. Binding of steroid receptor modulator (SRM) ligand leads to allosteric changes in SHR to exert positive or negative effects on the expression of target genes. Due, in part, to the fact that current SRMs generally target ligand binding domain (LBD)/AF2 and neglect intrinsically disordered (ID) N-terminal domain (NTD)/AF1, clinically relevant SRMs lack selectivity and are also prone to the development of resistance over time. Therefore, to maximize the efficacy of SHR-based therapeutics, the possibility of developing unique modulators that act to control AF1 activity must be considered. Recent studies targeting androgen receptor's (AR's) ID AF1 domain for the castration-resistant prostate cancer has provided the possibility of therapeutically targeting ID NTD/AF1 surfaces by allosteric modulations to achieve desired effects. In this review article, we discuss how inter- and intra- molecular allosteric regulations controlled by AR's structural flexibility and dynamics particularly the ID NTD/AF1 is an emerging area of investigation, which could be exploited for drug development and therapeutic targeting of prostate cancer. PMID- 27364547 TI - The contribution of toll-like receptor 2 on Helicobacter pylori activation of the nuclear factor-kappa B signaling pathway in gastric epithelial cells. AB - Helicobacter pylori (H. pylori) is a spiral shaped gram-negative bacterium that induces immune responses in the gastric mucosa. Toll-like receptors (TLRs) play important roles in mediating inflammatory cytokines by recognition of conserved molecular patterns on bacteria. Changes in the expression of toll-like receptor (TLR) 2, TLR4 and the relative inflammatory cytokines were analyzed in normal gastric epithelial GES-1 cells following treatment with H. pylori or Escherichia coli lipopolysaccharide (E. coli LPS) in order to investigate the contribution of TLRs in recognizing and mediating the inflammatory response to H. pylori, and study the differences in TLRs' performance between H. pylori and E. coli. Specific inhibitors for the declines in TLR2 and TLR4 were also employed. The results showed that H. pylori infection increased TLR2 expression in GES-1 cells, but TLR4 remained unchanged regardless of H. pylori or TLR2 small interfering RNA treatment. Furthermore, the secretion of cyclooxygenase-2 (COX-2) induced by H. pylori was inhibited by declines in TLR2, but not in TLR4. In conclusion, TLR2 plays an even more important role than TLR4 not only in recognizing H. pylori, but also in the induction of inflammatory cytokines initiated by H. pylori. However, both TLR2 and TLR4 are necessary in mediating the inflammatory response to E. coli LPS. PMID- 27364548 TI - Contribution of the outer membrane protein OmpW in Escherichia coli to complement resistance from binding to factor H. AB - The serum complement system is essential for innate immune defense against invading pathogenic bacteria. Some of the 8-stranded beta-barrel outer membrane proteins confer bacterial resistance to the innate host immunity. We have previously demonstrated that OmpW, also an 8-stranded beta-barrel protein that was identified a decade ago, protects bacteria against host phagocytosis. In this study, we investigated the complement resistance of OmpW. Our results indicate that the upregulation of OmpW is associated with increased survival when bacteria are exposed to normal human sera (NHS). Mutant bacteria lacking OmpW in NHS exhibited significantly lower survival rates in comparison to wild-type and ompW complemented bacteria. Furthermore, the bacterial survival significantly decreased in NHS that was supplemented with EGTA-Mg(2+) compared to that in NHS supplemented with EDTA. These results suggest that OmpW confer resistance to alternative complement pathway-mediated killing. Moreover, the binding of OmpW to factor H, a major inhibitor of alternative pathway, was found, indicating that OmpW recruitment of factor H is a mechanism for bacterial evasion of complement attack. PMID- 27364549 TI - Heart rate control by carvedilol in Japanese patients with chronic atrial fibrillation: The AF Carvedilol study. AB - BACKGROUND: beta-Blockers are used to control heart rate (HR) in patients with atrial fibrillation (AF). However, the appropriate dosage and efficacy of carvedilol in Japanese AF patients are yet to be clarified. METHODS: In this multicenter, randomized, double-blind study, Japanese patients with persistent or permanent AF received carvedilol for 6 weeks in the following three dosage regimen groups: 5-mg fixed-dose (n=42), 10-mg dose-escalation (n=42), or 20-mg dose-escalation (n=43). To evaluate the efficacy of each dosage regimen and the dose-response relationship, changes in 24-h mean HR (mHR) on Holter electrocardiograms from baseline to weeks 2, 4, and 6 were determined as primary endpoints. The effects on circadian changes in HR, the proportion of patients achieving target HR, clinical symptoms, and adverse events were also examined. RESULTS: After 2 weeks, carvedilol 5mg decreased 24-h mHR significantly [6.6 (95% CI: 5.2-8.0)beats/min, p<0.0001]. After 6 weeks, carvedilol showed a trend of dose-dependent HR reduction (p=0.0638): 7.6 (5.4-9.8) in the 5-mg fixed-dose group; 8.9 (6.7-11.1) in the 10-mg dose-escalation group; and 10.6 (8.4 12.8)beats/min in the 20-mg dose-escalation group. There were no serious adverse events related to carvedilol. CONCLUSIONS: In Japanese patients with persistent or permanent AF, carvedilol at 5mg once daily demonstrated a significant HR reduction, and step-wise dose escalation from 5mg to 20mg showed a trend of dose dependent HR reduction. PMID- 27364550 TI - Imaging of Esophageal Lymph Node Metastases by Desorption Electrospray Ionization Mass Spectrometry. AB - Histopathological assessment of lymph node metastases (LNM) depends on subjective analysis of cellular morphology with inter-/intraobserver variability. In this study, LNM from esophageal adenocarcinoma was objectively detected using desorption electrospray ionization-mass spectrometry imaging (DESI-MSI). Ninety lymph nodes (LN) and their primary tumor biopsies from 11 esophago-gastrectomy specimens were examined and analyzed by DESI-MSI. Images from mass spectrometry and corresponding histology were coregistered and analyzed using multivariate statistical tools. The MSIs revealed consistent lipidomic profiles of individual tissue types found within LNs. Spatial mapping of the profiles showed identical distribution patterns as per the tissue types in matched IHC images. Lipidomic profile comparisons of LNM versus the primary tumor revealed a close association in contrast to benign LN tissue types. This similarity was used for the objective prediction of LNM in mass spectrometry images utilizing the average lipidomic profile of esophageal adenocarcinoma. The multivariate statistical algorithm developed for LNM identification demonstrated a sensitivity, specificity, positive predictive value, and negative predictive value of 89.5%, 100%, 100%, and 97.2%, respectively, when compared with gold-standard IHC. DESI-MSI has the potential to be a diagnostic tool for perioperative identification of LNM and compares favorably with techniques currently used by histopathology experts. Cancer Res; 76(19); 5647-56. (c)2016 AACR. PMID- 27364551 TI - Tyrosine Phosphatase PTPRJ/DEP-1 Is an Essential Promoter of Vascular Permeability, Angiogenesis, and Tumor Progression. AB - The protein tyrosine phosphatase PTPRJ/DEP-1 has been implicated in negative growth regulation in endothelial cells, where its expression varies at transitions between proliferation and contact inhibition. However, in the same cells, DEP-1 has also been implicated in VEGF-dependent Src activation, permeability, and capillary formation, suggesting a positive role in regulating these functions. To resolve this dichotomy in vivo, we investigated postnatal angiogenesis and vascular permeability in a DEP-1-deficient mouse. In this study, we report that DEP-1 is required for Src activation and phosphorylation of its endothelial cell-specific substrate, VE-cadherin, after systemic injection of VEGF. Accordingly, VEGF-induced vascular leakage was abrogated in the DEP-1 deficient mice. Furthermore, capillary formation was impaired in murine aortic tissue rings or Matrigel plugs infused with VEGF. In the absence of DEP-1, angiogenesis triggered by ischemia or during tumor formation was defective, which in the latter case was associated with reduced tumor cell proliferation and increased apoptosis. Macrophage infiltration was also impaired, reflecting reduced vascular permeability in the tumors or a possible cell autonomous effect of DEP-1. Consequently, the formation of spontaneous and experimental lung metastases was strongly decreased in DEP-1-deficient mice. In clinical specimens of cancer, less vascularized tumors exhibited lower microvascular expression of DEP-1. Altogether, our results established DEP-1 as an essential driver of VEGF dependent permeability, angiogenesis, and metastasis, suggesting a novel therapeutic route to cancer treatment. Cancer Res; 76(17); 5080-91. (c)2016 AACR. PMID- 27364552 TI - Rapid Reprogramming of Primary Human Astrocytes into Potent Tumor-Initiating Cells with Defined Genetic Factors. AB - Cancer stem-like cells (CSC) are thought to drive brain cancer, but their cellular and molecular origins remain uncertain. Here, we report the successful generation of induced CSC (iCSC) from primary human astrocytes through the expression of defined genetic factors. Combined transduction of four factors, Myc, Oct-4, p53DD, and Ras, induced efficient transformation of primary human astrocytes into malignant cells with powerful tumor-initiating capabilities. Notably, transplantation of 100 transduced cells into nude mice was sufficient for tumor formation. The cells showed unlimited self-renewal ability with robust telomerase activities. In addition, they expressed typical glioma stem-like cell markers, such as CD133, CD15, and CD90. Moreover, these cells could form spheres in culture and differentiate into neuron-like, astrocyte-like, and oligodendrocyte-like cells. Finally, they also displayed resistance to the widely used brain cancer drug temozolomide. These iCSCs could provide important tools for studies of glioma biology and therapeutics development. Cancer Res; 76(17); 5143-50. (c)2016 AACR. PMID- 27364553 TI - Rebound Effects Caused by Withdrawal of MET Kinase Inhibitor Are Quenched by a MET Therapeutic Antibody. AB - MET oncogene amplification is emerging as a major mechanism of acquired resistance to EGFR-directed therapy in lung and colorectal cancers. Furthermore, MET amplification predicts responsiveness to MET inhibitors currently in clinical trials. Among the anti-MET drugs available, ATP-competitive small-molecule kinase inhibitors abrogate receptor autophosphorylation and downstream activation of ERK1/2 and AKT, resulting in cell-cycle arrest. However, this antiproliferative effect allows persistence of a pool of cancer cells that are quiescent but alive. Once the inhibition is removed, rebound activation of MET-driven cell proliferative pathways and tumor growth may occur, an adverse event observed frequently in clinical settings after drug discontinuation. Here we show that inhibitor withdrawal prompts receptor phosphorylation to levels higher than those displayed at steady-state and generates a rebound effect pushing quiescent cancer cells back into the cell cycle, both in vitro and in experimental tumor models in vivo Mechanistically, we found that inhibitor treatment blocks MET endocytosis, causing a local increase in the number of receptors at the plasma membrane. Upon inhibitor washout, the receptor is readily rephosphorylated. The initial phosphorylation is not only increased but also prolonged in duration due to downmodulation of a phosphatase-mediated MET-negative feedback loop, which accompanies receptor internalization. Notably, treatment with a MET therapeutic antibody that induces proteolytic cleavage of the receptor at the cell surface substantially prevents this rebound effect, providing a rationale to combine or alternate these mechanistically different types of MET-targeted therapy. Cancer Res; 76(17); 5019-29. (c)2016 AACR. PMID- 27364554 TI - BAFF and APRIL from Activin A-Treated Dendritic Cells Upregulate the Antitumor Efficacy of Dendritic Cells In Vivo. AB - The members of the TGFbeta superfamily play a key role in regulating developmental and homeostasis programs by controlling differentiation, proliferation, polarization, and survival of different cell types. Although the role of TGFbeta1 in inflammation and immunity is well evident, the contribution of other TGFbeta family cytokines in the modulation of the antitumor immune response remains less documented. Here we show that activin A triggers SMAD2 and ERK1/2 pathways in dendritic cells (DC) expressing type I and II activin receptors, and upregulates production of the TNFalpha family cytokines BAFF (TALL 1, TNFSF13B) and APRIL (TALL-2, TNFSF13A), which is blocked by SMAD2 and ERK1/2 inhibitors, respectively. BAFF and APRIL derived from activin A-treated DCs upregulate proliferation and survival of T cells expressing the corresponding receptors, BAFF-R and TACI. In vivo, activin A-stimulated DCs demonstrate a significantly increased ability to induce tumor-specific CTLs and inhibit the growth of melanoma and lung carcinoma, which relies on DC-derived BAFF and APRIL, as knockdown of the BAFF and APRIL gene expression in activin A-treated DCs blocks augmentation of their antitumor potential. Although systemic administration of activin A, BAFF, or APRIL for the therapeutic purposes is not likely due to the pluripotent effects on malignant and nonmalignant cells, our data open a novel opportunity for improving the efficacy of DC vaccines. In fact, a significant augmentation of the antitumor activity of DC pretreated with activin A and the proven role of DC-derived BAFF and APRIL in the induction of antitumor immunity in vivo support this direction. Cancer Res; 76(17); 4959-69. (c)2016 AACR. PMID- 27364555 TI - Metabolic Stress-Induced Phosphorylation of KAP1 Ser473 Blocks Mitochondrial Fusion in Breast Cancer Cells. AB - Mitochondrial dynamics during nutrient starvation of cancer cells likely exert profound effects on their capability for metastatic progression. Here, we report that KAP1 (TRIM28), a transcriptional coadaptor protein implicated in metastatic progression in breast cancer, is a pivotal regulator of mitochondrial fusion in glucose-starved cancer cells. Diverse metabolic stresses induced Ser473 phosphorylation of KAP1 (pS473-KAP1) in a ROS- and p38-dependent manner. Results from live-cell imaging and molecular studies revealed that during the first 6 to 8 hours of glucose starvation, mitochondria initially underwent extensive fusion, but then subsequently fragmented in a pS473-KAP1-dependent manner. Mechanistic investigations using phosphorylation-defective mutants revealed that KAP1 Ser473 phosphorylation limited mitochondrial hyperfusion in glucose-starved breast cancer cells, as driven by downregulation of the mitofusin protein MFN2, leading to reduced oxidative phosphorylation and ROS production. In clinical specimens of breast cancer, reduced expression of MFN2 corresponded to poor prognosis in patients. In a mouse xenograft model of human breast cancer, there was an association in the core region of tumors between MFN2 downregulation and the presence of highly fragmented mitochondria. Collectively, our results suggest that KAP1 Ser473 phosphorylation acts through MFN2 reduction to restrict mitochondrial hyperfusion, thereby contributing to cancer cell survival under conditions of sustained metabolic stress. Cancer Res; 76(17); 5006-18. (c)2016 AACR. PMID- 27364556 TI - Activation of the c-Met Pathway Mobilizes an Inflammatory Network in the Brain Microenvironment to Promote Brain Metastasis of Breast Cancer. AB - Brain metastasis is one of the chief causes of mortality in breast cancer patients, but the mechanisms that drive this process remain poorly understood. Here, we report that brain metastatic cells expressing high levels of c-Met promote the metastatic process via inflammatory cytokine upregulation and vascular reprogramming. Activated c-Met signaling promoted adhesion of tumor cells to brain endothelial cells and enhanced neovascularization by inducing the secretion of IL8 and CXCL1. Additionally, stimulation of IL1beta secretion by activation of c-Met induced tumor-associated astrocytes to secrete the c-Met ligand HGF. Thus, a feed-forward mechanism of cytokine release initiated and sustained by c-Met fed a vicious cycle that generated a favorable microenvironment for metastatic cells. Reinforcing our results, we found that pterostilbene, a compound that penetrates the blood-brain barrier, could suppress brain metastasis by targeting c-Met signaling. These findings suggest a potential utility of this natural compound for chemoprevention. Cancer Res; 76(17); 4970 80. (c)2016 AACR. PMID- 27364557 TI - Activation of Wnt/beta-Catenin in Ewing Sarcoma Cells Antagonizes EWS/ETS Function and Promotes Phenotypic Transition to More Metastatic Cell States. AB - Ewing sarcomas are characterized by the presence of EWS/ETS fusion genes in the absence of other recurrent genetic alterations and mechanisms of tumor heterogeneity that contribute to disease progression remain unclear. Mutations in the Wnt/beta-catenin pathway are rare in Ewing sarcoma but the Wnt pathway modulator LGR5 is often highly expressed, suggesting a potential role for the axis in tumor pathogenesis. We evaluated beta-catenin and LGR5 expression in Ewing sarcoma cell lines and tumors and noted marked intra- and inter-tumor heterogeneity. Tumors with evidence of active Wnt/beta-catenin signaling were associated with increased incidence of tumor relapse and worse overall survival. Paradoxically, RNA sequencing revealed a marked antagonism of EWS/ETS transcriptional activity in Wnt/beta-catenin-activated tumor cells. Consistent with this, Wnt/beta-catenin-activated cells displayed a phenotype that was reminiscent of Ewing sarcoma cells with partial EWS/ETS loss of function. Specifically, activation of Wnt/beta-catenin induced alterations to the actin cytoskeleton, acquisition of a migratory phenotype, and upregulation of EWS/ETS repressed genes. Notably, activation of Wnt/beta-catenin signaling led to marked induction of tenascin C (TNC), an established promoter of cancer metastasis, and an EWS/ETS-repressed target gene. Loss of TNC function in Ewing sarcoma cells profoundly inhibited their migratory and metastatic potential. Our studies reveal that heterogeneous activation of Wnt/beta-catenin signaling in subpopulations of tumor cells contributes to phenotypic heterogeneity and disease progression in Ewing sarcoma. Significantly, this is mediated, at least in part, by inhibition of EWS/ETS fusion protein function that results in derepression of metastasis associated gene programs. Cancer Res; 76(17); 5040-53. (c)2016 AACR. PMID- 27364558 TI - Syndecan-1 (CD138) Suppresses Apoptosis in Multiple Myeloma by Activating IGF1 Receptor: Prevention by SynstatinIGF1R Inhibits Tumor Growth. AB - Syndecan-1 (Sdc1/CD138) expression is linked to disease severity in multiple myeloma, although the causal basis for this link remains unclear. Here we report that capture of the IGF1 receptor (IGF1R) by Sdc1 suppresses ASK1-dependent apoptosis in multiple myeloma cells. Sdc1 binds two different fractions of IGF1R, one that is constitutively active and a second that is activated by IGF1 ligand. Notably, IGF1R kinase activity in both fractions is blocked by synstatinIGF1R (SSTNIGF1R), a peptide that inhibits IGF1R capture by Sdc1, as well as by a truncated peptide (SSTNIGF1R-T) that appears to be specific for multiple myeloma cells. Mechanistically, we show that ASK1 is bound to active IGF1R and inhibited by Tyr and Ser83/Ser966 phosphorylation. When IGF1R engagement with Sdc1 is blocked by SSTNIGF1R, ASK1 becomes activated, and initiates JNK- and caspase-3 mediated apoptosis. In pharmacologic tests, we find SSTNIGF1R is highly stable in human plasma and displays a half-life of 27 hours in mice, wherein it significantly reduces both the size and neovascularization of CAG myeloma tumor xenografts. Taken together, our results offer a preclinical proof of concept and mechanistic rationale for the exploration of SSTNIGF1R as an experimental therapeutic to dually attack multiple myeloma tumor cell survival and tumor angiogenesis. Cancer Res; 76(17); 4981-93. (c)2016 AACR. PMID- 27364559 TI - MEF2D Transduces Microenvironment Stimuli to ZEB1 to Promote Epithelial Mesenchymal Transition and Metastasis in Colorectal Cancer. AB - Epithelial-mesenchymal transition (EMT) is an essential mechanism of metastasis, including in colorectal cancer. Although EMT processes are often triggered in cancer cells by their surrounding microenvironment, how EMT-relevant genes control these processes is not well understood. In multiple types of cancers, the transcription factor MEF2D has been implicated in cell proliferation, but its contributions to metastasis have not been addressed. Here, we show MEF2D is overexpressed in clinical colorectal cancer tissues where its high expression correlates with metastatic process. Functional investigations showed that MEF2D promoted cancer cell invasion and EMT and that it was essential for certain microenvironment signals to induce EMT and metastasis in vivo Mechanistically, MEF2D directly regulated transcription of the EMT driver gene ZEB1 and facilitated histone acetylation at the ZEB1 promoter. More importantly, MEF2D responded to various tumor microenvironment signals and acted as a central integrator transducing multiple signals to activate ZEB1 transcription. Overall, our results define a critical function for MEF2D in upregulating EMT and the metastatic capacity of colorectal cancer cells. Further, they offer new insights into how microenvironment signals activate EMT-relevant genes and deepen the pathophysiologic significance of MEF2D, with potential implications for the prevention and treatment of metastatic colorectal cancer. Cancer Res; 76(17); 5054-67. (c)2016 AACR. PMID- 27364560 TI - Trends of contact lens prescribing in Jordan. AB - PURPOSE: To evaluate contact lens prescribing trends among optometrists in Jordan. METHODS: Optometrists from 173 practices in Jordan were surveyed about prescribing contact lenses in their practice. Practitioners were required to record information for the last 10 patients that visited their practice. Demographic data such as age and gender was obtained for each patient. In addition, data relating to lens type, lens design, replacement methods and the care regime advised to each patient were recorded. Practitioners were required to provide information relating to their education and years of experience. The influence of education and experience with respect to lens prescribing trends was explored using linear regression models for the proportions of lens types fitted for patients. RESULTS: A total of 1730 contact lens fits were analyzed. The mean (+/-SD) age of lens wearers was 26.6 (+/-7.9) years, of whom 65% were female. Conventional hydrogel lenses were the most prescribed lenses, accounting for 60.3% of the fits, followed by silicone hydrogel lenses (31.3%), and rigid lenses (8.4%). In terms of lens design, spherical lenses appeared to be most commonly prescribed on monthly basis. Daily disposable lenses were second most prescribed lens modality, accounting for 20.4% of the study sample. Multi-purpose solution (MPS) was the preferred care regimen, with a prevalence of 88.1% reported in the study sample, compared to hydrogen peroxide (1-step and 2-step), which represented only 2.8% of the patients in this study. A relationship was established between the two educational groups for rigid lens prescribing (F=17.4, p<0.0001), while the experience of the optometrist was not a significant factor (F=0.4, p=0.54). CONCLUSION: This work has provides an up-to-date analysis of contact lens prescribing trends among optometrists in Jordan. Contact lens prescribing in terms of lens type, lens design, modality of wear and care regimen agree with global market trends with small variations. This report will help practitioners and the industry to detect any deficiencies in the contact lens market in Jordan, which will ease implementing current and future plans in developing contact lens practice and patient eye care in the region. PMID- 27364561 TI - gammaH2AX and p53 responses in TK6 cells discriminate promutagens and nongenotoxicants in the presence of rat liver S9. AB - Previous work with a diverse set of reference chemicals suggests that an in vitro multiplexed flow cytometry-based assay (MultiFlowTM DNA Damage Kit-p53, gammaH2AX, Phospho-Histone H3) can distinguish direct-acting clastogens and aneugens from nongenotoxicants (Bryce SM et al. []: Environ Mol Mutagen 57:171 189). This work extends this line of investigation to include compounds that require metabolic activation to form reactive electrophiles. For these experiments, TK6 cells were exposed to 11 promutagens and 37 presumed nongenotoxicants in 96 well plates. Unless precipitation or foreknowledge about cytotoxicity suggested otherwise, the highest concentration was 1 mM. Exposure occurred for 4 hr after which time cells were washed to remove S9 and test article. Immediately following the wash and again at 24 hr, cell aliquots were added to wells of a microtiter plate containing the working detergent/stain/antibody cocktail. After a brief incubation, robotic sampling was employed for walk-away flow cytometric data acquisition. Univariate logistic regression analyses indicated that gammaH2AX induction and p53 activation provide the greatest degree of discrimination between clastogens and nongenotoxicants. Multivariate prediction algorithms that incorporated both of these endpoints, in each combination of time points, were evaluated. The best performing models correctly predicted 9 clastogens out of 11 and 36 nongenotoxicants out of 37. These results are encouraging as they suggest that an efficient and highly scalable multiplexed assay can effectively identify clastogenic chemicals that require bioactivation. More work is planned with a broader range of chemicals, additional cell lines, and other laboratories to further evaluate the merits and limitations of this approach. Environ. Mol. Mutagen. 57:546-558, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27364562 TI - Facilitation through altered resource availability in a mixed-species rodent malaria infection. AB - A major challenge in disease ecology is to understand how co-infecting parasite species interact. We manipulate in vivo resources and immunity to explain interactions between two rodent malaria parasites, Plasmodium chabaudi and P. yoelii. These species have analogous resource-use strategies to the human parasites Plasmodium falciparum and P. vivax: P. chabaudi and P. falciparum infect red blood cells (RBC) of all ages (RBC generalist); P. yoelii and P. vivax preferentially infect young RBCs (RBC specialist). We find that: (1) recent infection with the RBC generalist facilitates the RBC specialist (P. yoelii density is enhanced ~10 fold). This occurs because the RBC generalist increases availability of the RBC specialist's preferred resource; (2) co-infections with the RBC generalist and RBC specialist are highly virulent; (3) and the presence of an RBC generalist in a host population can increase the prevalence of an RBC specialist. Thus, we show that resources shape how parasite species interact and have epidemiological consequences. PMID- 27364563 TI - Synergistic Effect of H2O2 and NO2 in Cell Death Induced by Cold Atmospheric He Plasma. AB - Cold atmospheric pressure plasmas (CAPPs) have emerged over the last decade as a new promising therapy to fight cancer. CAPPs' antitumor activity is primarily due to the delivery of reactive oxygen and nitrogen species (RONS), but the precise determination of the constituents linked to this anticancer process remains to be done. In the present study, using a micro-plasma jet produced in helium (He), we demonstrate that the concentration of H2O2, NO2(-) and NO3(-) can fully account for the majority of RONS produced in plasma-activated buffer. The role of these species on the viability of normal and tumour cell lines was investigated. Although the degree of sensitivity to H2O2 is cell-type dependent, we show that H2O2 alone cannot account for the toxicity of He plasma. Indeed, NO2(-), but not NO3(-), acts in synergy with H2O2 to enhance cell death in normal and tumour cell lines to a level similar to that observed after plasma treatment. Our findings suggest that the efficiency of plasma treatment strongly depends on the combination of H2O2 and NO2(-) in determined concentrations. We also show that the interaction of the He plasma jet with the ambient air is required to generate NO2(-) and NO3(-) in solution. PMID- 27364564 TI - Molecular detection and characterization through analysis of the hexon and fiber genes of Adenoviruses causing conjunctivitis in Tunisia, North Africa. AB - Human adenoviruses (HAdVs) are common causes of conjunctivitis. This study describes the epidemiological features and characterizes by phylogenetic analysis HAdVs isolated from patients with conjunctivitis in Tunisia, North Africa. Data on out-patients presenting with conjunctivitis during 2 years (2012-2013) were analyzed. Conjunctival swabs obtained from 240 patients were assessed for the presence of HAdVs by PCR amplification on the fiber and hexon genes. Positive PCR products, together with those of nine viral isolates from previous years, were sequenced and analyzed phylogenetically. Conjunctivitis represented 11.5% of all reasons of consultations with a slight increase between mid-March and mid-June. Sixty-five percent of samples (n = 156) revealed positive by at least one PCR test. PCR amplification in the hexon gene was slightly more sensitive as compared to the fiber gene. Genotyping in the two genomic regions gave concordant results for almost all isolates. HAdV-D8 was the most predominant genotype (87.6%) and was detected continuously from 2000 to 2013. Minor co-circulating genotypes including HAdV-E4, HAdV-B3, HAdV-B55, and HAdV-D37 were identified; most of them were detected by amplification in the hexon gene. In conclusion, this work reports molecular data on adenoviral conjunctivitis from a region where such information is scarce and contributes to a better knowledge of the worldwide distribution of causative genotypes. It revealed a predominance and endemic circulation of HAdV-D8, a genotype that was mainly reported from epidemic keratoconjunctivitis. It shows that PCR amplification in two different genomic regions enhances the sensitivity of HAdV detection in clinical samples and the identification of minor genotypes. J. Med. Virol. 89:304-312, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27364565 TI - Erythropoietin-regulated oxidative stress negatively affects enucleation during terminal erythropoiesis. AB - Differentiating erythroblasts are exposed to an oxidative environment. The dynamics of oxidative status during terminal erythropoiesis and how they affect cell differentiation in response to erythropoietin (Epo) are unclear. Here, we show that Epo induces reactive oxygen species (ROS) production in the early stages of terminal erythropoiesis. The levels of ROS correlate with CD71 surface expression and the uptake of iron and transferrin. ROS decreases in the late stages of terminal erythropoiesis, when the cells are preparing for enucleation. Consistently, treatment of erythroblasts with a low dose (5 mM) of N-acetyl cysteine (NAC), a ROS scavenger, promotes enucleation. However, a high dose (20 mM) of NAC leads to significant cell death. Our study reveals an important function of Epo in regulating the dynamics of oxidative status and enucleation. PMID- 27364567 TI - Eye tracking reveals the cost of switching between self and other perspectives in a visual perspective-taking task. AB - Previous studies have shown that while people can rapidly and accurately compute their own and other people's visual perspectives, they experience difficulty ignoring the irrelevant perspective when the two perspectives differ. We used the "avatar" perspective-taking task to examine the mechanisms that underlie these egocentric (i.e., interference from their own perspective) and altercentric (i.e., interference from the other person's perspective) tendencies. Participants were eye-tracked as they verified the number of discs in a visual scene according to either their own or an on-screen avatar's perspective. Crucially in some trials the two perspectives were inconsistent (i.e., each saw a different number of discs), while in others they were consistent. To examine the effect of perspective switching, performance was compared for trials that were preceded with the same versus a different perspective cue. We found that altercentric interference can be reduced or eliminated when participants stick with their own perspective across consecutive trials. Our eye-tracking analyses revealed distinct fixation patterns for self and other perspective taking, suggesting that consistency effects in this paradigm are driven by implicit mentalizing of what others can see, and not automatic directional cues from the avatar. PMID- 27364566 TI - Clinical pharmacology of analgosedatives in neonates: ways to improve their safe and effective use. AB - OBJECTIVES: To propose approaches tailored to the specific needs of neonates, such as structured product development programmes, with the ultimate goal to improve the safe and effective use of analgosedatives in these fragile patients. KEY FINDINGS: The feasibility and relevance of a structured product development programme in neonates (optimal study design based on preliminary data; model development; internal, external and prospective evaluation; an individualized dosing regimen; long-term safety; pharmacogenetics) are illustrated for the use of morphine. Based on changes in clinical practices, similar development plans are in progress for short-acting analgosedatives such as propofol, but are in need of tailored pharmacodynamic tools to assess and quantify effects. Furthermore, for drugs like paracetamol where there is already sufficient clinical pharmacology knowledge, attention needs to be given to long-term safety aspects. Finally, new covariates such as pharmacogenetics might further improve neonatal pain management, but clearly need to be integrated with other well established covariates like age or weight. SUMMARY: Product development programmes for analgosedatives in neonates are needed. These programmes should be tailored to their specific needs (short-acting sedation, pain relief), should include long-term safety and should incorporate the exploration of newer covariates like pharmacogenetics. PMID- 27364568 TI - Safety and immunogenicity of inactivated poliovirus vaccine when given with measles-rubella combined vaccine and yellow fever vaccine and when given via different administration routes: a phase 4, randomised, non-inferiority trial in The Gambia. AB - BACKGROUND: The introduction of the inactivated poliovirus vaccine (IPV) represents a crucial step in the polio eradication endgame. This trial examined the safety and immunogenicity of IPV given alongside the measles-rubella and yellow fever vaccines at 9 months and when given as a full or fractional dose using needle and syringe or disposable-syringe jet injector. METHODS: We did a phase 4, randomised, non-inferiority trial at three periurban government clinics in west Gambia. Infants aged 9-10 months who had already received oral poliovirus vaccine were randomly assigned to receive the IPV, measles-rubella, and yellow fever vaccines, singularly or in combination. Separately, IPV was given as a full intramuscular or fractional intradermal dose by needle and syringe or disposable syringe jet injector at a second visit. The primary outcomes were seroprevalence rates for poliovirus 4-6 weeks post-vaccination and the rate of seroconversion between baseline and post-vaccination serum samples for measles, rubella, and yellow fever; and the post-vaccination antibody titres generated against each component of the vaccines. We did a per-protocol analysis with a non-inferiority margin of 10% for poliovirus seroprevalence and measles, rubella, and yellow fever seroconversion, and (1/3) log2 for log2-transformed antibody titres. This trial is registered with ClinicalTrials.gov, number NCT01847872. FINDINGS: Between July 10, 2013, and May 8, 2014, we assessed 1662 infants for eligibility, of whom 1504 were enrolled into one of seven groups for vaccine interference and one of four groups for fractional dosing and alternative route of administration. The rubella and yellow fever antibody titres were reduced by co-administration but the seroconversion rates achieved non-inferiority in both cases (rubella, 4.5% [95% CI -9.5 to -0.1]; yellow fever, 1.2% [-2.9 to 5.5]). Measles and poliovirus responses were unaffected (measles, 6.8% [95% CI -1.4 to 14.9]; poliovirus serotype 1, 1.6% [-6.7 to 4.7]; serotype 2, 0.0% [-2.1 to 2.1]; serotype 3, 0.0% [-3.8 to 3.9]). Poliovirus seroprevalence was universally high (>97%) after vaccination, but the antibody titres generated by fractional intradermal doses of IPV did not achieve non-inferiority compared with full dose. The number of infants who seroconverted or had a four-fold rise in titres was also lower by the intradermal route. There were no safety concerns. INTERPRETATION: The data support the future co-administration of IPV, measles rubella, and yellow fever vaccines within the Expanded Programme on Immunization schedule at 9 months. The administration of single fractional intradermal doses of IPV by needle and syringe or disposable-syringe jet injector compromises the immunity generated, although it results in a high post-vaccination poliovirus seroprevalence. FUNDING: Bill & Melinda Gates Foundation. PMID- 27364569 TI - Correction: Acute inhibition of neurosteroid estrogen synthesis suppresses status epilepticus in an animal model. PMID- 27364570 TI - Serum lactate levels and perfusion index: are these prognostic factors on mortality and morbidity in very low-birth weight infants? AB - AIM: Early hemodynamic assessment of global parameters in critically ill newborns fails and requires mostly invasive measurements in neonatal intensive care unit. Clinical signs are frequently used for assessment of peripheral perfusion. Perfusion index (PI) is a new noninvasive numerical value of peripheral perfusion. Serum lactate levels and PI are the indicators that are important in determining prognosis of preterm infants. In this study, we aimed to investigate the relationship of serum lactate levels and PI with mortality and morbidity in very low-birth weight infants (VLBW). STUDY DESIGN: This study was conducted between July 2014 and July 2015 in a Level III NICU. The study enrolled preterm infants with a gestational age <= 32 weeks, birth weight <= 1500 g. Serum lactate levels from blood gases and PI, SpO2 measurements were recorded at 1st, 12th and 24th hours by using a new generation pulse-oximeter. Morbidities and mortalities were documented. RESULTS: A total of 60 VLBW infants were enrolled the study. Mean birth weight and gestational age were 991 +/- 288 g and 27.5 +/- 2.5 w, respectively. Retinopathy of prematurity (ROP) was significantly higher in the patients with high lactate levels (>4 mg/dl) at 1st hour and low-PI levels (<0.5) at 12th hour of life (p = 0.042, p = 0.015), respectively. Bronchopulmonary displasia (BPD) was significantly higher in the patients with low PI (< 0.5) at 1st hour. Lactate and PI values were not significantly correlated with necrotizing enterocolitis, intraventricular hemorrhage, patent ductus arteriosus, sepsis and mortality. CONCLUSION: High lactate levels (> 4 mg/dl) and low PI (< 0.5) could be used as early parameters for prediction of ROP and BPD. This data suggests that in VLBW infants lactate levels and PI parameters during the first 24 h will be effective in determining the prognosis of the disease. We believe that larger, randomized controlled clinical trials are likely to establish the true benefit. PMID- 27364571 TI - Dual gradients of light intensity and nutrient concentration for full-factorial mapping of photosynthetic productivity. AB - Optimizing bioproduct generation from microalgae is complicated by the myriad of coupled parameters affecting photosynthetic productivity. Quantifying the effect of multiple coupled parameters in full-factorial fashion requires a prohibitively high number of experiments. We present a simple hydrogel-based platform for the rapid, full-factorial mapping of light and nutrient availability on the growth and lipid accumulation of microalgae. We accomplish this without microfabrication using thin sheets of cell-laden hydrogels. By immobilizing the algae in a hydrogel matrix we are able to take full advantage of the continuous spatial chemical gradient produced by a diffusion-based gradient generator while eliminating the need for chambers. We map the effect of light intensities between 0 MUmol m(-2) s(-1) and 130 MUmol m(-2) s(-1) (~28 W m(-2)) coupled with ammonium concentrations between 0 mM and 7 mM on Chlamydomonas reinhardtii. Our data set, verified with bulk experiments, clarifies the role of ammonium availability on the photosynthetic productivity Chlamydomonas reinhardtii, demonstrating the dependence of ammonium inhibition on light intensity. Specifically, a sharp optimal growth peak emerges at approximately 2 mM only for light intensities between 80 and 100 MUmol m(-2) s(-1)- suggesting that ammonium inhibition is insignificant at lower light intensities. We speculate that this phenomenon is due to the regulation of the high affinity ammonium transport system in Chlamydomonas reinhardtii as well as free ammonia toxicity. The complexity of this photosynthetic biological response highlights the importance of full factorial data sets as enabled here. PMID- 27364572 TI - MicroRNA-145 functions as a tumor suppressor by targeting matrix metalloproteinase 11 and Rab GTPase family 27a in triple-negative breast cancer. AB - Although increasing evidence has documented that microRNA-145 (miR-145) acts as a tumor suppressor in breast cancer, its exact role in triple-negative breast cancer (TNBC) remains poorly defined. In this study, the expression of miR-145 in human TNBC cells and samples from 30 patients was analyzed by stem-loop real-time PCR. We found that miR-145 was significantly downregulated in TNBC tissues and cells. Upregulating miR-145 in HCC1937 cells dramatically suppressed cell proliferation and induced G1-phase arrest, whereas MDA-MB-231 cells did not show growth inhibition. MiR-145 exhibited an inhibitory role in cell invasion through the post-transcriptional regulation of the novel targets MMP11 and Rab27a in TNBC cells. Additionally, miR-145 silencing could be reversed by 5-aza-2' deoxycytidine (DAC). These results demonstrated that miR-145 has an inhibitory role in TNBC malignancy by targeting MMP11 and Rab27a, which might be potential therapeutic and diagnostic targets for TNBC. PMID- 27364573 TI - Antiproliferative effect of a synthetic aptamer mimicking androgen response elements in the LNCaP cell line. AB - Prostate cancer usually develops to a hormone-refractory state that is irresponsive to conventional therapeutic approaches. Therefore, new methods for treating aggressive prostate cancer are under development. Because of the importance of androgen receptors (ARs) in the development of the hormone refractory state and AR mechanism of action, this study was designed. A single stranded DNA as an aptamer was designed that could mimic the hormone response element (HRE). The LNCaP cells as an AR-rich model were divided into three sets of triplicate groups: the test group was transfected with Aptamer Mimicking HRE (AMH), Mock received only transfection reagents (mock) and a negative control. All three sets received 0, 10 and 100 nM of dehydroepiandrosterone (DHEA) separately. Data analysis showed hormone dependency of LNCaP cells in the negative control group upon treatment with 10 and 100 nM DHEA (compared with cells left untreated (P=0.001)). Transfection of AMH resulted in significant reduction of proliferation in the test group when compared with the negative control group with 10 (P=0.001) or 100 nM DHEA (P=0.02). AMH can form a hairpin structure at 37 degrees C and mimic the genomic HRE. Hence, it is capable of effectively competing with genomic HRE and interrupting the androgen signaling pathway in a prostate cancer cell line (LNCaP). PMID- 27364575 TI - Mesorectal Invasion Depth in Rectal Carcinoma Is Associated With Low Survival. AB - BACKGROUND: Most cases of rectal cancer (RC) in our institution are in pathologic stage T3. They are a heterogeneous group but have been classified in a single stage category. We performed the present study to validate the prognostic significance of the mesorectal extension depth (MED) in T3 RC measured in millimeters beyond the muscularis propria plane. MATERIALS AND METHODS: We performed a retrospective analysis of 104 patients with T3 RC who had undergone curative surgery after a course of preoperative chemoradiotherapy at a tertiary referral cancer hospital. The patients were grouped by MED (T3a, < 1 mm; T3b, 1-5 mm; T3c > 5-10 mm; and T3d > 10 mm). The clinicopathologic data and disease-free survival were analyzed. RESULTS: The 5-year disease-free survival rate according to the T3 subclassification was 87.5% for those with T3a, 57.9% for T3b, 38.7% for T3c, and 40.3% for those with T3d tumors (P = .050). On univariate and multivariate analysis, the prognostic factors affecting survival were overall recurrence (hazard ratio [HR], 3.670; 95% confidence interval [CI], 1.710-7.837; P = .001), histologic grade (HR, 2.204; 95% CI, 1.156-4.199; P = .016), mesorectal invasion depth (HR, 1.885; 95% CI, 1.164-3.052; P = .010), and lymph node metastasis (HR, 1.211; 95% CI, 1.015-1.444; P = .033). CONCLUSION: MED is a significant prognostic factor in patients with T3 RC who have undergone neoadjuvant chemoradiotherapy, especially when the MED is > 5 mm. The MED could be as important as other clinicopathologic factors in predicting disease-specific survival. PMID- 27364574 TI - Locked nucleic acid anti-miR-21 inhibits cell growth and invasive behaviors of a colorectal adenocarcinoma cell line: LNA-anti-miR as a novel approach. AB - Colorectal cancer (CRC) is the third leading cause of cancer-related death and has an extremely poor prognosis. Dysregulation of microRNAs (miRNAs) has been shown to be involved in the pathogenesis and progression of many malignancies. Recent data suggest that microRNA-21 (miR-21) is significantly elevated in different types of cancer, especially colon adenocarcinoma. Against this background, locked nucleic acid (LNA)-modified oligonucleotides have recently been suggested as a novel approach for targeting miRNAs as antisense-based gene silencing. The aim of the current study was to explore the functional role of LNA anti-miR-21 in a colon adenocarcinoma LS174T cell line. LS174T cells were transfected with LNA-anti-miR-21 for 24, 48 and 72 h. Quantitative real-time reverse transcriptase-PCR (qRT-PCR) was performed to assess miR-21 expression by LNA-anti-miR-21. The viability of the cells was evaluated by MTT (3-[4, 5 dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay and Annexin V/propidium iodide staining assay was used to detect apoptosis. Moreover, invasive behavior of the cells was evaluated before and after therapy by transwell assay. LNA-anti-miR-21 was successfully transfected in human LS174T cells and suppressed the endogenous miR-21. LNA-anti-miR-21 inhibited the cells' growth followed by induction of apoptosis. LNA-anti-miR-21 (50 pmol/MUl) reduced the invasive behaviors of LS174T cells after 24 h, compared with untreated cells and scrambled LNA-transfected cells. However, this effect was more pronounced after 72 h. Our findings suggest the therapeutic potential of LNA-anti-miR-21 in a colon adenocarcinoma for targeting miR-21 expression. Further studies are warranted to investigate the molecular mechanisms underlying this novel inhibitor in colorectal cancer to establish its potential value for treatment of CRC patients with high miR-21 expression. PMID- 27364594 TI - Molecular Transport Junctions Created By Self-Contacting Gapped Nanowires. AB - Molecular transport junctions (MTJs) are important components in molecular electronic devices. However, the synthesis of MTJs remains a significant challenge, as the dimensions of the junction must be tailored for each experiment, based on the molecular lengths. A novel methodology is reported for forming MTJs, taking advantage of capillary and van der Waals forces. PMID- 27364593 TI - Paraoxonase 2 modulates a proapoptotic function in LS174T cells in response to quorum sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone. AB - A mucus layer coats the gastrointestinal tract and serves as the first line of intestinal defense against infection. N-acyl-homoserine lactone (AHL) quorum sensing molecules produced by gram-negative bacteria in the gut can influence the homeostasis of intestinal epithelium. In this study, we investigated the effects of two representative long- and short-chain AHLs, N-3-(oxododecanoyl)-homoserine lactone (C12-HSL) and N-butyryl homoserine lactone (C4-HSL), on cell viability and mucus secretion in LS174T cells. C12-HSL but not C4-HSL significantly decreased cell viability by inducing mitochondrial dysfunction and activating cell apoptosis which led to a decrease in mucin expression. Pretreatment with lipid raft disruptor (Methyl-beta-cyclodextrin, MbetaCD) and oxidative stress inhibitor (N-acetyl-L-cysteine, NAC) slightly rescued the viability of cells damaged by C12-HSL exposure, while the paraoxonase 2 (PON2) inhibitor (Triazolo[4,3-a]quinolone, TQ416) significantly affected recovering cells viability and mucin secretion. When LS174T cells were treated with C12-HSL and TQ416 simultaneously, TQ416 showed the maximal positive effect on cells viability. However, if cells were first treated with C12-HSL for 40 mins, and then TQ46 was added, the TQ416 had no effect on cell viability. These results suggest that the C12-HSL-acid process acts at an early step to activate apoptosis as part of C12-HSL's effect on intestinal mucus barrier function. PMID- 27364595 TI - Chondro-protective effects of low intensity pulsed ultrasound. AB - OBJECTIVES: Cartilage is a highly mechano-responsive tissue. Chondrocytes undergo a series of complex changes, including proliferation and metabolic alteration as the target of external biomechanical and biochemical stimuli. IL-1beta is known to regulate chondrocyte metabolism and plays an important role in the pathogenesis of osteoarthritis (OA). The objective of this study was to employ low-intensity pulsed ultrasound (LIPUS) as a localized mechanical stimulus and assess its effects on chondrocyte migration, proliferation, metabolism, and differentiation, as well as its ability to suppress IL-1beta mediated catabolism in cartilage. METHODS: Human cartilage explants and chondrocytes were stimulated by LIPUS in the presence and absence of IL-1beta to asses cartilage degradation, chondrocytes metabolism, migration, and proliferation. Western blot analyses were conducted to study IL-1beta the associated NFkappaB pathway in chondrocytes. RESULTS: LIPUS stimulation increased the proteoglycan content in human cartilage explants and inhibited IL-1beta induced loss of proteoglycans. LIPUS stimulation increased rates of chondrocyte migration and proliferation, and promoted chondrogenesis in mesenchymal stem cells (MSC). Further, LIPUS suppressed IL 1beta induced activation of phosphorylation of NFkappaB-p65 and IKBalpha leading to reduced expression of MMP13 and ADAMT5 in chondrocytes. CONCLUSIONS: Collectively, these data demonstrate the potential therapeutic effects of LIPUS in preventing cartilage degradation and treating OA via a mechanical stimulation that inhibits the catabolic action of IL-1beta and stimulates chondrocyte migration, proliferation, and differentiation. PMID- 27364597 TI - Obesity: Inheritance via mitochondria. PMID- 27364596 TI - Targeting ID2 expression triggers a more differentiated phenotype and reduces aggressiveness in human salivary gland cancer cells. AB - Inhibitors of DNA-binding (ID) proteins are negative regulators of basic helix loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. We previously determined that ID1 was highly expressed in aggressive salivary gland cancer (SGC) cells in culture. Here, we show that ID2 is also expressed in aggressive SGC cells. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. Moreover, ID2 knockdown almost completely suppresses invasion and the expression of matrix metalloproteinase 9. In conclusion, ID2 expression maintains an aggressive phenotype in SGC cells, and ID2 repression triggers a reduction in cell aggressiveness. ID2 therefore represents a potential therapeutic target during SGC progression. ID proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. ID2 therefore represents a potential therapeutic target during SGC progression. PMID- 27364599 TI - Adipose tissue: Sex differences in adipogenesis. PMID- 27364598 TI - Subclinical hypothyroidism in childhood - current knowledge and open issues. AB - Subclinical hypothyroidism is defined as serum levels of TSH above the upper limit of the reference range, in the presence of normal concentrations of total T4 or free T4. This biochemical profile might be an indication of mild hypothyroidism, with a potential increased risk of metabolic abnormalities and cardiovascular disease recorded among adults. Whether subclinical hypothyroidism results in adverse health outcomes among children is a matter of debate and so management of this condition remains challenging. Mild forms of untreated subclinical hypothyroidism do not seem to be associated with impairments in growth, bone health or neurocognitive outcome. However, ongoing scientific investigations have highlighted the presence of subtle proatherogenic abnormalities among children with modest elevations in their TSH levels. Although current findings are insufficient to recommend levothyroxine treatment for all children with mild asymptomatic forms of subclinical hypothyroidism, they highlight the potential need for assessment of cardiovascular risk among children with this condition. Increased understanding of the early metabolic risk factors associated with subclinical hypothyroidism in childhood will help to improve the management of affected individuals. PMID- 27364600 TI - Capturing tumor complexity in vitro: Comparative analysis of 2D and 3D tumor models for drug discovery. AB - Two-dimensional (2D) cell cultures growing on plastic do not recapitulate the three dimensional (3D) architecture and complexity of human tumors. More representative models are required for drug discovery and validation. Here, 2D culture and 3D mono- and stromal co-culture models of increasing complexity have been established and cross-comparisons made using three standard cell carcinoma lines: MCF7, LNCaP, NCI-H1437. Fluorescence-based growth curves, 3D image analysis, immunohistochemistry and treatment responses showed that end points differed according to cell type, stromal co-culture and culture format. The adaptable methodologies described here should guide the choice of appropriate simple and complex in vitro models. PMID- 27364601 TI - Effect of diastolic dysfunction on postoperative outcomes after cardiovascular surgery: A systematic review and meta-analysis. AB - OBJECTIVE: The objective of this study was to investigate the effect of preoperative diastolic dysfunction on postoperative mortality and morbidity after cardiovascular surgery. METHODS: We systematically searched for articles that assessed the prognostic role of diastolic dysfunction on cardiovascular surgery in PubMed, Cochrane Library, Web of Science, Embase, and Scopus until February 2016. Twelve studies (n = 8224) met our inclusion criteria. Because of the scarcity of outcome events, fixed-effects meta-analysis was performed via the Mantel-Haenszel method. RESULTS: Preoperative diagnosis of diastolic dysfunction was associated with greater postoperative mortality (odds ratio [OR], 2.41; 95% confidence interval [CI], 1.54-3.71; P < .0001), major adverse cardiac events (OR, 2.07; 95% CI, 1.55-2.78; P <= .0001), and prolonged mechanical ventilation (OR, 2.08; 95% CI, 1.04-4.16; P = .04) compared with patients without diastolic dysfunction among patients who underwent cardiovascular surgery. The odds of postoperative myocardial infarction (OR, 1.29; 95% CI, 0.82-2.05; P = .28) and atrial fibrillation (OR, 2.67; 95% CI, 0.49-14.43; P = .25) did not significantly differ between the 2 groups. Severity of preoperative diastolic dysfunction was associated with increased postoperative mortality (OR, 21.22; 95% CI, 3.74 120.33; P = .0006) for Grade 3 diastolic dysfunction compared with patients with normal diastolic function. Inclusion of left ventricular ejection fraction (LVEF) <40% accompanying diastolic dysfunction did not further impact postoperative mortality (P = .27; I(2) = 18%) compared with patients with normal LVEF and diastolic dysfunction. CONCLUSIONS: Presence of preoperative diastolic dysfunction was associated with greater postoperative mortality and major adverse cardiac events, regardless of LVEF. Mortality was significantly greater in grade III diastolic dysfunction. PMID- 27364602 TI - Hypometabolism as the ultimate defence in stress response: how the comparative approach helps understanding of medically relevant questions. AB - First conceptualized from breath-hold diving mammals, later recognized as the ultimate cell autonomous survival strategy in anoxia-tolerant vertebrates and burrowing or hibernating rodents, hypometabolism is typically recruited by resilient organisms to withstand and recover from otherwise life-threatening hazards. Through the coordinated down-regulation of biosynthetic, proliferative and electrogenic expenditures at times when little ATP can be generated, a metabolism turned 'down to the pilot light' allows the re-balancing of energy demand with supply at a greatly suppressed level in response to noxious exogenous stimuli or seasonal endogenous cues. A unifying hallmark of stress-tolerant organisms, the adaptation effectively prevents lethal depletion of ATP, thus delineating a marked contrast with susceptible species. Along with disengaged macromolecular syntheses, attenuated transmembrane ion shuttling and PO2 conforming respiration rates, the metabolic slowdown in tolerant species usually culminates in a non-cycling, quiescent phenotype. However, such a reprogramming also occurs in leading human pathophysiologies. Ranging from microbial infections through ischaemia-driven infarcts to solid malignancies, cells involved in these disorders may again invoke hypometabolism to endure conditions non-permissive for growth. At the same time, their reduced activities underlie the frequent development of a general resistance to therapeutic interventions. On the other hand, a controlled induction of hypometabolic and/or hypothermic states by pharmacological means has recently stimulated intense research aimed at improved organ preservation and patient survival in situations requiring acutely administered critical care. The current review article therefore presents an up to-date survey of concepts and applications of a coordinated and reversibly down regulated metabolic rate as the ultimate defence in stress responses. PMID- 27364604 TI - A realistic fabrication and design concept for quantum gates based on single emitters integrated in plasmonic-dielectric waveguide structures. AB - Tremendous enhancement of light-matter interaction in plasmonic-dielectric hybrid devices allows for non-linearities at the level of single emitters and few photons, such as single photon transistors. However, constructing integrated components for such devices is technologically extremely challenging. We tackle this task by lithographically fabricating an on-chip plasmonic waveguide structure connected to far-field in- and out-coupling ports via low-loss dielectric waveguides. We precisely describe our lithographic approach and characterize the fabricated integrated chip. We find excellent agreement with rigorous numerical simulations. Based on these findings we perform a numerical optimization and calculate concrete numbers for a plasmonic single-photon transistor. PMID- 27364606 TI - Reputation in an economic game modulates premotor cortex activity during action observation. AB - Our interactions with other people - and our processing of their actions - are shaped by their reputation. Research has identified an Action Observation Network (AON) which is engaged when observing other people's actions. Yet, little is known about how the processing of others' actions is influenced by another's reputation. Is the response of the AON modulated by the reputation of the actor? We developed a variant of the ultimatum game in which participants watched either the visible or occluded actions of two 'proposers'. These actions were tied to decisions of how to split a pot of money although the proposers' decisions on each trial were not known to participants when observing the actions. One proposer made fair offers on the majority of trials, establishing a positive reputation, whereas the other made predominantly, unfair offers resulting in a negative reputation. We found significant activations in two regions of the left dorsal premotor cortex (dPMC). The first of these showed a main effect of reputation with greater activation for the negative reputation proposer than the positive reputation proposer. Furthermore individual differences in trust ratings of the two proposers covaried with activation in the right primary motor cortex (M1). The second showed an interaction between visibility and reputation driven by a greater effect of reputation when participants were observing an occluded action. Our findings show that the processing of others' actions in the AON is modulated by an actor's reputation, and suggest a predictive role for the PMC during action observation. PMID- 27364603 TI - The COPD Assessment Test: Can It Discriminate Across COPD Subpopulations? AB - BACKGROUND: The COPD Assessment Test (CAT) is a valid disease-specific questionnaire measuring health status. However, knowledge concerning its use regarding patient and disease characteristics remains limited. Our main objective was to assess the degree to which the CAT score varies and can discriminate between specific patient population groups. METHODS: The Canadian Cohort Obstructive Lung Disease (CanCOLD) is a random-sampled, population-based, multicenter, prospective cohort that includes subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] classifications 1 to 3). The CAT questionnaire was administered at three visits (baseline, 1.5 years, and 3 years). The CAT total score was determined for sex, age groups, smoking status, GOLD classification, exacerbations, and comorbidities. RESULTS: A total of 716 subjects with COPD were included in the analysis. The majority of subjects (72.5%) were not previously diagnosed with COPD. The mean FEV1/FVC ratio was 61.1 +/- 8.1%, with a mean FEV1 % predicted of 82.3 +/- 19.3%. The mean CAT scores were 5.8 +/- 5.0, 9.6 +/- 6.7, and 16.1 +/- 10.0 for GOLD 1, 2, and 3+ classifications, respectively. Higher CAT scores were observed in women, current smokers, ever-smokers, and subjects with a previous diagnosis of COPD. The CAT was also able to distinguish between subjects who experience exacerbations vs those who had no exacerbation. CONCLUSIONS: These results suggest that the CAT, originally designed for use in clinically symptomatic patients with COPD, can also be used in individuals with mild airflow obstruction and newly diagnosed COPD. In addition, the CAT was able to discriminate between sexes and subjects who experience frequent and infrequent exacerbations. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00920348; Study ID No.: IRO-93326. PMID- 27364607 TI - Sum Frequency Generation of Interfacial Lipid Monolayers Shows Polarization Dependence on Experimental Geometries. AB - Sum frequency generation (SFG) vibrational spectroscopy has been widely employed to investigate molecular structures of biological surfaces and interfaces including model cell membranes. A variety of lipid monolayers or bilayers serving as model cell membranes and their interactions with many different molecules have been extensively studied using SFG. Here, we conducted an in-depth investigation on polarization-dependent SFG signals collected from interfacial lipid monolayers using different experimental geometries, i.e., the prism geometry (total internal reflection) and the window geometry (external reflection). The different SFG spectral features of interfacial lipid monolayers detected using different experimental geometries are due to the interplay between the varied Fresnel coefficients and second-order nonlinear susceptibility tensor terms of different vibrational modes (i.e., ss and as modes of methyl groups), which were analyzed in detail in this study. Therefore, understanding the interplay between the interfacial Fresnel coefficients and chi((2)) tensors is a prerequisite for correctly understanding the SFG spectral features with respect to different experimental geometries. More importantly, the derived information in this paper should not be limited to the methyl groups with a C3v symmetry; valid extension to interfacial functional groups with different molecular symmetries and even chiral interfaces could be expected. PMID- 27364608 TI - Structural effects of modified ribonucleotides and magnesium in transfer RNAs. AB - Modified nucleotides are ubiquitous and important to tRNA structure and function. To understand their effect on tRNA conformation, we performed a series of molecular dynamics simulations on yeast tRNAPhe and tRNAinit, Escherichia coli tRNAinit and HIV tRNALys. Simulations were performed with the wild type modified nucleotides, using the recently developed CHARMM compatible force field parameter set for modified nucleotides (J. Comput. Chem.2016, 37, 896), or with the corresponding unmodified nucleotides, and in the presence or absence of Mg2+. Results showed a stabilizing effect associated with the presence of the modifications and Mg2+ for some important positions, such as modified guanosine in position 37 and dihydrouridines in 16/17 including both structural properties and base interactions. Some other modifications were also found to make subtle contributions to the structural properties of local domains. While we were not able to investigate the effect of adenosine 37 in tRNAinit and limitations were observed in the conformation of E. coli tRNAinit, the presence of the modified nucleotides and of Mg2+ better maintained the structural features and base interactions of the tRNA systems than in their absence indicating the utility of incorporating the modified nucleotides in simulations of tRNA and other RNAs. PMID- 27364610 TI - Doxifluridine-conjugated 2-5A analog shows strong RNase L activation ability and tumor suppressive effect. AB - RNase L is activated by 2',5'-oligoadenylates (2-5A) at subnanomolar levels to cleave single-stranded RNA. We previously reported the hypothesis that the introduction of an 8-methyladenosine residue at the 2'-terminus of the 2-5A tetramer shifts the 2-5A binding site of RNase L. In this study, we synthesized various 5'-modified 2-5A analogs with 8-methyladenosine at the 2'-terminus. The doxifluridine-conjugated 8-methyladenosine-substituted 2-5A analog was significantly more effective as an activator of RNase L than the parent 5' monophophorylated 2-5A tetramer and showed a tumor suppressive effect against human cervical cancer cells. PMID- 27364609 TI - Development of CNS multi-receptor ligands: Modification of known D2 pharmacophores. AB - Several known D2 pharmacophores have been explored as templates for identifying ligands with multiple binding affinities at dopamine and serotonin receptors considered as clinically relevant receptors in the treatment of neuropsychiatric diseases. This approach has resulted in the identification of ligands that target multiple CNS receptors while avoiding others associated with deleterious effects. In particular, compounds 11, 15 and 22 may have potential for further development as antipsychotic agents as they favorably interact with the clinically relevant receptors including D2R, 5-HT1AR, and 5-HT7R. We have also identified the pair of compounds 11 and 10 as high affinity D2R ligands with and without SERT binding affinities, respectively. These differential binding profiles endow the pair with the potential for evaluating SERT contributions to antipsychotic drug activity in animal behavioral models. In addition, compound 11 has no significant affinity for 5-HT2CR and binds only moderately to the H1R, suggesting it may not induce weight gain or sedation when used clinically. Taken together, compound 11 displays an interesting pharmacological profile that necessitates the evaluation of its functional and in vivo effects in animal models which are currently ongoing. PMID- 27364611 TI - Design, synthesis, and pharmacological evaluation of JDTic analogs to examine the significance of replacement of the 3-hydroxyphenyl group with pyridine or thiophene bioisosteres. AB - The potent and selective KOR antagonist JDTic was derived from the N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine class of pure opioid antagonists. In previous studies we reported that compounds that did not have a hydroxyl on the 3-hydroxyphenyl group and did not have methyl groups at the 3- and 4-position of the piperidine ring were still potent and selective KOR antagonists. In this study we report JDTic analogs 2, 3a-b, 4a-b, and 5, where the 3-hydroxyphenyl ring has been replaced by a 2-, 3-, or 4-pyridyl or 3-thienyl group and do not have the 3-methyl or 3,4-dimethyl groups, remain potent and selective KOR antagonists. Of these, (3R)-7-hydroxy-N-(1S)-2-methyl-[4-methyl-4 pyridine-3-yl-carboxamide (3b) had the best overall binding potency and selectivity in a [(35)S]GTPgammaS functional assay, with a Ke=0.18nM at the KOR and 273- and 16,700-fold selectivity for the KOR relative to the MOR and DOR, respectively. Calculated physiochemical properties for 3b suggest that it will cross the blood-brain barrier. PMID- 27364612 TI - Keeping you at arm's length: modifying peripersonal space influences interpersonal distance. AB - Peripersonal space represents the area around the body where objects are coded in motor terms for the purpose of voluntary goal-directed actions. Previous studies have suggested that peripersonal space is also a safe space linked with our private area, influencing interpersonal space in social contexts. However, whether these two spaces rely on similar embodied processes remains an open issue. In the present study, participants observed a point-light walker (PLW) approaching them from different directions and passing near them at different distances from their right or left shoulder. While approaching, the PLW disappeared at a distance of 2 m and the task for the participants was to estimate if the interpersonal distance, at the time the PLW would have reached their level, was comfortable or not. Between two sessions of comfort judgments, the participants manipulated a 70 cm tool entailing an extension of peripersonal space, or a 10 cm tool entailing no extension of peripersonal space. The results revealed that the comfortable interpersonal distance was larger when the PLW crossed the mid-sagittal plane of the participants than when it approached them laterally, with a concomitant increase of response time. After participants manipulated the long tool, comfortable interpersonal distance increased, but predominantly when the PLW trajectory implied crossing the participants' mid sagittal plane. This effect was not observed when participants manipulated the short tool. Two control tasks showed that using the long tool modified the reachability (control 1), but not the time to passage (control 2) estimates of PLW stimuli, suggesting that tool use extended peripersonal space without changing perceived visual distances. Overall, the data show that comfortable interpersonal distance is linked to the representation of peripersonal space. As a consequence, increasing peripersonal space through tool use has the immediate consequence that comfortable interpersonal distance from another person also increases, suggesting that interpersonal-comfort space and peripersonal-reaching space share a common motor nature. PMID- 27364614 TI - Editorial: Getting the Whole Picture, Seeing the Trees and the Forest. PMID- 27364613 TI - GM-CSF and GM-CSF receptor have regulatory role in transforming rat mesenteric mesothelial cells into macrophage-like cells. AB - OBJECTIVE AND DESIGN: During peritonitis, mesothelial cells assume macrophage characteristics, expressing macrophage markers, indicating that they might differentiate into macrophage-like cells. MATERIALS AND SUBJECTS: Twenty-five male rats were used for in vivo experiments. For in vitro experiments, a primary mesentery culture model was developed. The mesothelial cell to macrophage-like cell transition was followed by studying ED1 expression. TREATMENTS: In vitro primary mesenteric culture was treated with granulocyte-macrophage colony stimulating factor (GM-CSF, 1 ng/ml). Blocking internalization of receptor-ligand complex, Dynasore (80 uM) was used. Acute peritonitis was induced by Freund's adjuvant's (1 ml) intraperitoneal injection. RESULTS: Immunohistochemistry: GM CSF in vitro treatment resulted in a prominent ED1 expression in transformed mesothelial cells. Blocking the internalization, ED1 expression could not be detected. GM-CSF receptor (both alpha and beta) was expressed in mesothelial cells in vitro (even if the GM-CSF was not present) and in vivo. Inflammation resulted in an increasing GM-CSF and GM-CSF-receptor level in the lysate of mesothelial cells. CONCLUSIONS: Mesothelial cells can differentiate into macrophage-like cells, and GM-CSF, produced by the mesothelial cells, has probably an autocrine regulatory role in this transition. Our results provide new data about the plasticity of mesothelial cell and support the idea that during inflammation macrophages can derive from non-hematopoietic sources as well. PMID- 27364615 TI - Loss of Hippocampal Oligodendrocytes Contributes to the Deficit of Contextual Fear Learning in Adult Rats Experiencing Early Bisphenol A Exposure. AB - During early development, continuous exposure to environmental contaminants such as bisphenol A (BPA) is known to alter neuronal development, resulting in aberrant brain structure and predisposing individuals to developing neuropsychiatric disorders later in life. While the altered oligodendrocyte (OL) structure and function have been casually linked to the occurrence of numerous psychiatric diseases, it remains open whether early BPA exposure (EBE) also recruits OLs to mediate its toxicity in the brain. Here, we observed that EBE from birth to postnatal day 21 caused a substantial loss of hippocampal OLs in rat pups. The OL loss was enduring and manifested even when the affected pups spanned into their adulthood. In parallel, the expression of two key proteins in mature OLs, myelin basic protein (MBP), and monocarboxylate transporter 1 (MCT1) was markedly downregulated in adult hippocampus with a considerable reduction in the number of myelinated axons. By contrast, the myelination of individual axons remained intact. The altered hippocampal OLs were related to EBE-mediated disruption of estrogen receptor (ER) signaling in developing OLs and could be readily prevented by treatment with low level of ICI 182780, an ER antagonist. Importantly, the adult rats subject to EBE exhibited clear deficit in contextual fear memory, which highly correlated with OL loss and decreased MBP and MCT1 expression in hippocampus. The OL loss may thus represent an alternative route through which EBE has its adversity on the brain and contributes to the development of neuropsychiatric illness. PMID- 27364616 TI - Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and Mycophenolate. AB - BACKGROUND AND OBJECTIVES: IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent for induction therapy in renal transplantation. However, this remains controversial in deceased donor renal transplantation (DDRT) maintained on tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied the United Network for Organ Sharing Registry for patients receiving DDRT from 2000 to 2012 maintained on TAC/MPA at transplantation hospital discharge (n=74,627) to compare outcomes of IL2-RA and other induction agents. We initially divided the cohort into two groups on the basis of steroid use at the time of discharge: steroid (n=59,010) versus no steroid (n=15,617). Each group was stratified into induction categories: IL2-RA, rabbit antithymocyte globulin (r-ATG), alemtuzumab, and no induction. The main outcomes were incidence of acute rejection within the first year and overall graft failure (defined as graft failure and/or death) post transplantation. Propensity score (PS), specifically inverse probability of treatment weight, analysis was used to minimize selection bias caused by nonrandom assignment of induction therapies. RESULTS: Median (25th, 75th percentiles) follow-up times were 3.9 (1.1, 5.9) and 3.2 (1.1, 4.9) years for steroid and no steroid groups, respectively. Acute rejection within the first year and overall graft failure within 5 years of transplantation were more common in the no induction category (13.3%; P<0.001 and 28%; P=0.01, respectively) in the steroid group and the IL2-RA category (11.1%; P=0.16 and 27.4%; P<0.001, respectively) in the no steroid group. Compared with IL2-RA, PS-weighted and covariate-adjusted multivariable logistic and Cox analyses showed that outcomes in the steroid group were similar among induction categories, except that acute rejection was significantly lower with r-ATG (odds ratio [OR], 0.68; 95% confidence interval [95% CI], 0.62 to 0.74). In the no steroid group, compared with IL2-RA, odds of acute rejection with r-ATG (OR, 0.80; 95% CI, 0.60 to 1.00) and alemtuzumab (OR, 0.68; 95% CI, 0.53 to 0.88) were lower, and r-ATG was associated with better graft survival (hazard ratio, 0.86; 95% CI, 0.75 to 0.99). CONCLUSIONS: In DDRT, compared with IL2-RA induction, no induction was associated with similar outcomes when TAC/MPA/steroids were used. r-ATG seems to offer better graft survival over IL2-RA in steroid avoidance protocols. PMID- 27364617 TI - Effect of water-immersion restraint stress on tryptophan catabolism through the kynurenine pathway in rat tissues. AB - The aim of this study was to clarify the effect of water-immersion restraint stress (WIRS) on tryptophan (Trp) catabolism through the kynurenine (Kyn) pathway in rat tissues. The tissues of rats subjected to 6 h of WIRS (+WIRS) had increased tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) activities and increased TDO and IDO1 (one of two IDO isozymes in mammals) mRNA expression levels, with decreased Trp and increased Kyn contents in the liver. +WIRS rats had unchanged TDO and IDO activities in the kidney, decreased TDO activity and unchanged IDO activity in the brain, and unchanged IDO activity in the lung and spleen, with increased Kyn content in all of these tissues. Pretreatment of stressed rats with RU486, a glucocorticoid antagonist, attenuated the increased TOD activity, but not the increased IDO activity, with partial recoveries of the decreased Trp and increased Kyn contents in the liver. These results indicate that WIRS enhances hepatic Trp catabolism by inducing both IDO1 and TDO in rats. PMID- 27364618 TI - A comparison of four techniques to measure anterior and posterior vertebral body heights and sagittal plane wedge angles in adolescent idiopathic scoliosis. AB - Adolescent idiopathic scoliosis (AIS) is a three-dimensional (3D) spinal deformity of unknown aetiology. Increased growth of the anterior part of the vertebrae known as anterior overgrowth has been proposed as a potential driver for AIS initiation and progression. To date, there has been no objective evaluation of the 3D measurement techniques used to identify this phenomenon and the majority of previous studies use 2D planar assessments which contain inherent projection errors due to the vertebral rotation which is part of the AIS deformity. In this study, vertebral body (VB) heights and wedge angles were measured in a test group of AIS patients and healthy controls using four different image analysis and measurement techniques. Significant differences were seen between the techniques in terms of VB heights and VB wedge angles. The low variability, and the fact that the rotation and tilt of the deformed VBs are taken into account, suggests that the proposed technique using the full 3D orientation of the vertebrae is the most reliable method to measure anterior and posterior VB heights and sagittal plane wedge angles in 3D image data sets. These results have relevance for future investigations that aim to quantify anterior overgrowth in AIS patients for comparison with healthy controls. PMID- 27364619 TI - An evaluation of the accuracy and precision of methane prediction equations for beef cattle fed high-forage and high-grain diets. AB - The study determined the performance of equations to predict enteric methane (CH4) from beef cattle fed forage- and grain-based diets. Many equations are available to predict CH4 from beef cattle and the predictions vary substantially among equations. The aims were to (1) construct a database of CH4 emissions for beef cattle from published literature, and (2) identify the most precise and accurate extant CH4 prediction models for beef cattle fed diets varying in forage content. The database was comprised of treatment means of CH4 production from in vivo beef studies published from 2000 to 2015. Criteria to include data in the database were as follows: animal description, intakes, diet composition and CH4 production. In all, 54 published equations that predict CH4 production from diet composition were evaluated. Precision and accuracy of the equations were evaluated using the concordance correlation coefficient (r c ), root mean square prediction error (RMSPE), model efficiency and analysis of errors. Equations were ranked using a combined index of the various statistical assessments based on principal component analysis. The final database contained 53 studies and 207 treatment means that were divided into two data sets: diets containing ?400 g/kg dry matter (DM) forage (n=116) and diets containing ?200 g/kg DM forage (n=42). Diets containing between ?400 and ?200 g/kg DM forage were not included in the analysis because of their limited numbers (n=6). Outliers, treatment means where feed was fed restrictively and diets with CH4 mitigation additives were omitted (n=43). Using the high-forage dataset the best-fit equations were the International Panel on Climate Change Tier 2 method, 3 equations for steers that considered gross energy intake (GEI) and body weight and an equation that considered dry matter intake and starch:neutral detergent fiber with r c ranging from 0.60 to 0.73 and RMSPE from 35.6 to 45.9 g/day. For the high-grain diets, the 5 best-fit equations considered intakes of metabolisable energy, cellulose, hemicellulose and fat, or for steers GEI and body weight, with r c ranging from 0.35 to 0.52 and RMSPE from 47.4 to 62.9 g/day. Ranking of extant CH4 prediction equations for their accuracy and precision differed with forage content of the diet. When used for cattle fed high-grain diets, extant CH4 prediction models were generally imprecise and lacked accuracy. PMID- 27364621 TI - [Literature search is not a minor matter]. PMID- 27364622 TI - [German neurology and neurologists during the Third Reich: Preconditions and general framework before and after 1933]. AB - This article focuses on the institutional development of neurology in Germany up to the rise to power of the National Socialists and the radical sociopolitical changes after 1933. A wide range of scattered secondary literature was assessed and evaluated. Additionally, some original sources are literally quoted and interpreted according to the context. Since the end of the nineteenth century a complicated process of separation from internal medicine and psychiatry led to the formation of a self-conscious discipline of neurology. The first generation of German neurologists succeeded in founding the German Journal for Neurology ("Deutsche Zeitschrift fur Nervenheilkunde") in 1890 and their own neurological association, the Society of German Neurologists ("Gesellschaft Deutscher Nervenarzte", GDN) in 1907. On an international scale, however, the institutional implementation of neurology with only a small number of chairs and few neurology departments remained more than modest. The ambitions for autonomy ended 2 years after the change of power in 1933. Regulatory interventions by the government and psychiatric interests led to the fusion of the GDN with the psychiatric specialist society, the new association being called the Society of German Neurologists and Psychiatrists ("Gesellschaft Deutscher Neurologen und Psychiater", GDNP) in 1935. In this group psychiatrists dominated the discourse. The expulsion, imprisonment and murder of physicians declared as non-Aryan or Jewish along with the forced consolidation ("Gleichschaltung") at the universities prompted profound changes in medical and academic life. It remains an ongoing challenge of neurological historical research to measure the impact of this upheaval on the few neurology departments in hospitals and private practices. PMID- 27364624 TI - Generation of a novel chimeric PALFn antigen of Bacillus anthracis and its immunological characterization in mouse model. AB - Bacillus anthracis chimeric molecule PALFn, comprising the immunodominant domains of protective antigen (PA) and lethal factor (LF), has been developed in the past and has been shown to confer enhanced protection against anthrax in mouse model when challenged with anthrax lethal toxin (LeTx). However, the immunological correlates for this chimeric antigen, both in terms of humoral as well as cell mediated immune responses, have not been described in detail. To address this gap, we have determined the immunological responses both at humoral as well as cellular levels for the protection conferred by the novel chimeric antigen PALFn constructed in our laboratory in comparison to PA antigen. The biological functionality of the chimeric antigen was ascertained by the trypsin digestion assay. The trypsin cleavage activated the functionality of PALFn and rendered it to interact and bind with the LF molecule. Similarly, the LFn component in the chimera could independently interact and bind to the trypsin-activated wild-type PA. Further, it was observed that the PALFn-immunized mice sera could readily react to both PA and LF antigens while PA-immunized mice sera showed reaction to PA and PALFn alone and not to the individual LF antigen. The in vitro toxin neutralizing ability of PALFn antisera on macrophage cell line J774.1 was robust but with 1.3-fold lesser titer than PA-immunized antisera. PALFn-immunized mouse splenocytes showed a significant lymphocyte proliferation when stimulated with PALFn. There was a remarkable increase in the level of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin 10 (IL-10), interferon-gamma (IFN- gamma), and tumor necrosis factor alpha (TNFalpha) from PALFn- and PA-stimulated splenocytes. In addition, there was a significant increase in antigen-specific CD4+ and CD8+ T cell counts from both PALFn- and PA-immunized mouse splenocytes. The results clearly demonstrate the ability of chimeric molecule PALFn in eliciting robust humoral and cell-mediated immune responses in mouse model that is parallel to the wild-type PA but has additional anti-LF antibody response. Considering the enhanced protection offered by the chimera PALFn, we can conclude that it can be a better alternative to the wild-type PA-based recombinant vaccine against anthrax. PMID- 27364625 TI - Conversion of apple pomace waste to ethanol at industrial relevant conditions. AB - Apple pomace samples were evaluated for conversion to ethanol at industrial relevant conditions. Biomass degradation efficiency by commercial enzymes was evaluated at 20 % solid loading for dilute sulfuric acid, calcium oxide, and autoclave without any chemical (control) apple pomace samples. The control and calcium oxide-pretreated pomace provided similar sugar yields, while dilute sulfuric acid pretreatment resulted in reduced sugar yields. The control and calcium oxide-pretreated pomace hydrolysate were fermented to ethanol using a native Saccharomyces cerevisiae yeast strain, producing 38.8 and 36.9 g/L of ethanol, respectively. When control apple pomace sample loading was increased from 20 to 30 %, 57.5 and 50.1 g/L of glucose and fructose was produced, respectively. Lastly, we found that unhydrolyzed solids (UHS) present during fermentation had little effect on ethanol yield, as 53.6 and 53.8 g/L of ethanol were produced with and without UHS, respectively. Overall, ethanol yields were 134 g per kg of dry apple pomace. A complete process mass balance for enzyme hydrolysis and ethanol fermentation is provided in this manuscript. These results show that apple pomace is an excellent feedstock for producing ethanol that could be either used as biofuel or as beverage. PMID- 27364620 TI - Early goal-directed therapy in severe sepsis and septic shock: insights and comparisons to ProCESS, ProMISe, and ARISE. AB - Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was largely incorporated into the first 6 hours of sepsis management (resuscitation bundle) adopted by the Surviving Sepsis Campaign and disseminated internationally as the standard of care for early sepsis management. Recently a trio of trials (ProCESS, ARISE, and ProMISe), while reporting an all-time low sepsis mortality, question the continued need for all of the elements of early goal-directed therapy or the need for protocolized care for patients with severe and septic shock. A review of the early hemodynamic pathogenesis, historical development, and definition of early goal-directed therapy, comparing trial conduction methodology and the changing landscape of sepsis mortality, are essential for an appropriate interpretation of these trials and their conclusions. PMID- 27364626 TI - Fungi as a source of natural coumarins production. AB - Natural coumarins and derivatives are compounds that occur naturally in several organisms (plant, bacteria, and fungi) consisting of fused benzene and alpha pyrone rings. These compounds show high technological potential applications in agrochemical, food, pharmaceuticals, and cosmetics industries. Therefore, the need for bulk production of coumarins and the advancement of the chemical and pharmaceutical industries led to the development of synthetic coumarin. However, biotransformation process, synthetic bioengineering, metabolic engineering, and bioinformatics have proven effective in the production of natural products. Today, these biological systems are recognized as green chemistry innovation and business strategy. This review article aims to report the potential of fungi for synthesis of coumarin. These microorganisms are described as a source of natural products capable of synthesizing many bioactive metabolites. The features, classification, properties, and industrial applications of natural coumarins as well as new molecules obtained by basidiomycetes and ascomycetes fungi are reported in order to explore a topic not yet discussed in the scientific literature. PMID- 27364623 TI - Assessing stool quantities generated by three specific Kato-Katz thick smear templates employed in different settings. AB - BACKGROUND: The Kato-Katz technique is recommended for the diagnosis of helminth infections in epidemiological surveys, drug efficacy studies and monitoring of control interventions. We assessed the comparability of the average amount of faeces generated by three Kato-Katz templates included in test kits from two different providers. METHODS: Nine hundred Kato-Katz thick smear preparations were done; 300 per kit. Empty slides, slides plus Kato-Katz template filled with stool and slides plus stool after careful removal of the template were weighed to the nearest 0.1 mg. The average amount of stool that was generated on the slide was calculated for each template, stratified by standard categories of stool consistency (i.e. mushy, soft, sausage-shaped, hard and clumpy). RESULTS: The average amount of stool generated on slides was 40.7 mg (95 % confidence interval (CI): 40.0-41.4 mg), 40.3 mg (95 % CI: 39.7-40.9 mg) and 42.8 mg (95 % CI: 42.2 43.3 mg) for the standard Vestergaard Frandsen template, and two different templates from the Chinese Center for Disease Control and Prevention (China CDC), respectively. Mushy stool resulted in considerably lower average weights when the Vestergaard Frandsen (37.0 mg; 95 % CI: 34.9-39.0 mg) or new China CDC templates (37.4 mg; 95 % CI: 35.9-38.9 mg) were used, compared to the old China CDC template (42.2 mg; 95 % CI: 40.7-43.7 mg) and compared to other stool consistency categories. CONCLUSION: The average amount of stool generated by three specific Kato-Katz templates was similar (40.3-42.8 mg). Since the multiplication factor is somewhat arbitrary and small changes only have little effect on infection intensity categories, it is suggested that the standard multiplication factor of 24 should be kept for the calculation of eggs per gram of faeces for all investigated templates. PMID- 27364627 TI - Improving Bioengineering Student Leadership Identity Via Training and Practice within the Core-Course. AB - The development of a leadership identity has become significant in bioengineering education as a result of an increasing emphasis on teamwork within the profession and corresponding shifts in accreditation criteria. Unsurprisingly, placing bioengineering students in teams to complete classroom-based projects has become a dominant pedagogical tool. However, recent research indicates that engineering students may not develop a leadership identity, much less increased leadership capacity, as a result of such efforts. Within this study, we assessed two similar sections of an introductory course in bioengineering; each placed students in teams, while one also included leadership training and leadership practice. Results suggest that students in the leadership intervention section developed a strong self-image of themselves as leaders compared to students in the control section. These data suggest that creating mechanisms for bioengineering students to be trained in leadership and to practice leadership behaviors within a classroom team may be keys for unlocking leadership development. PMID- 27364629 TI - Differences in aqueous concentrations of cytokines in paediatric and adult patients with Coats' disease. AB - PURPOSE: To investigate the differential aqueous concentrations of vascular endothelia growth factor (VEGF) and inflammatory cytokines in paediatric and adult patients with Coats' disease. METHODS: A total of 20 eyes of 20 patients with Coats' disease, 12 eyes of 12 paediatric patients, and eight eyes of eight adult patients, six patients (six eyes) with congenital cataract as the paediatric control group and 10 patients (10 eyes) with senile cataract as the adult control group were examined. Aqueous humour samples were assessed for interleukin-6, -8, -1beta (IL-6, IL-8, IL-1beta, respectively), basic fibroblast growth factor, monocyte chemo-attractant protein 1, tumour necrosis factor alpha and VEGF by multiplex bead assay. RESULTS: Significantly, higher concentrations of VEGF, IL-6 and IL-1beta were found in the paediatric patients with Coats' disease (p = 0.001, p = 0.004 and p = 0.006). Concentration of VEGF in the paediatric patients with Stage 3B of Coats' disease was significantly higher than that of Stage 3A (p = 0.010). In the adult patients with Coats' disease, the aqueous levels of IL-6 and IL-1beta were significantly higher than that of the controls (p = 0.012, and p = 0.005). The concentration of IL-6 was significantly linearly associated with the extent of exudative retinal detachment (p = 0.003, R = 0.892). CONCLUSIONS: Increasing severity of Coats' disease is significantly associated with intraocular VEGF concentration in the paediatric patients. And IL 6 may be involved with the inflammatory process in the adult patients with Coats' disease. PMID- 27364628 TI - Association of semen cytokines with reactive oxygen species and histone transition abnormalities. AB - PURPOSE: The aim of this study is to investigate the relationships among reactive oxygen species (ROS) elevation, histone transition, and seminal cytokine concentrations. METHODS: Total levels of ROS in semen samples from 6560 men were measured. From this sample, 118 cases with high ROS and 106 controls were recruited. Basic semen parameters and histone-to-protamine ratios were analyzed, 400 semen cytokine and receptor alterations were assayed by protein chip, and finally 18 cytokines were validated in each sample using a Bio-Plex Cytokine assay. RESULTS: The results showed that the seminal ROS concentration was associated with abnormalities in the sperm histone transition. Compared with controls, 93 cytokines had significant alterations in the high ROS cases, with 14 of them further verified in individual samples. The concentrations of CXCL5, CXCL16, CXCL8, IL-1b, IL-10, CSF3, CCL3, and TNF-alpha were significantly correlated with the histone transition ratio. In addition, IL-16 showed significantly different concentrations in controls, normal semen with high ROS levels, and abnormal semen with high ROS levels. CONCLUSIONS: Semen ROS are associated with abnormalities in sperm histone transition. CXCL5, CXCL8, IL-16, CCL8, CCL22, CCL20, CXCL16, IL-1B, IL-6, IL-7, IL-10, CSF3, CCL3, CCL4, and TNF alpha all have elevated concentrations in semen with high ROS levels. These data might help to explain the mechanisms behind the increase in the levels of ROS and seminal cytokines and their relationship with defective spermatogenesis. PMID- 27364630 TI - Anti-cancer efficacy of nonthermal plasma dissolved in a liquid, liquid plasma in heterogeneous cancer cells. AB - The therapeutic potential of nonthermal plasma for cancer treatment has been reported recently. The heterogeneity of cancer cells need to be addressed to design effective anticancer treatments. Here, we show that treatment with nonthermal atmospheric-pressure plasma dissolved in a liquid (liquid plasma) induces oxidative stress in heterogeneous populations of cancer cells and ultimately kills these cells via apoptosis, regardless of genetic status, e.g., mutations in p53 and other DNA-damage-response genes. We found that liquid plasma markedly increased the concentration of intracellular and mitochondrial reactive oxygen species (ROS), reflecting an influx from the extracellular milieu. Liquid plasma contributed to mitochondrial accumulation of ROS and depolarization of mitochondrial membrane potential with consequent cell death. Healthy normal cells, however, were hardly affected by the liquid-plasma treatment. The antioxidant N-acetylcysteine blocked liquid-plasma-induced cell death. A knockdown of CuZn-superoxide dismutase or Mn-SOD enhanced the plasma-induced cell death, whereas expression of exogenous CuZn-SOD, Mn-SOD, or catalase blocked the cell death. These results suggest that the mitochondrial dysfunction mediated by ROS production is a key contributor to liquid-plasma-induced apoptotic cell death, regardless of genetic variation. Thus, liquid plasma may have clinical applications, e.g., the development of therapeutic strategies and prevention of disease progression despite tumor heterogeneity. PMID- 27364632 TI - Pacific Island Pharmacovigilance: The Need for a Different Approach. AB - Many Pacific Island countries (PICs) are recipients of funding support from the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund). However, most of these countries cannot be expected to meet Global Fund and World Health Organization (WHO) minimum requirements for a functioning pharmacovigilance (PV) system. We argue that a different approach is required to move PV forward in such countries. Although the long-term aim is to build adequate national PV capacity, we propose an approach in which resources are focused initially towards ensuring a proper system for the reporting of "problems with medicines" such as substandard and counterfeit products. The limited health system resources in these countries require that PV will be supported by some of the organizations also giving funding aid for the supply of medicines. PMID- 27364631 TI - Chemical exchange saturation transfer (CEST) imaging with fast variably accelerated sensitivity encoding (vSENSE). AB - PURPOSE: The widespread clinical use of chemical exchange saturation transfer (CEST) imaging is hampered by relatively long scan times due to its requirement that multiple saturation-offset image frames be acquired. Here, a novel variably accelerated sensitivity encoding (vSENSE) method is proposed that provides faster CEST acquisition than conventional SENSE. THEORY AND METHODS: The vSENSE method fully samples one CEST saturation frame, then undersamples the other frames variably. The fully-sampled frame, in conjunction with newly proposed incoherence absorption and artifact suppression strategies, improves the accuracy of sensitivity maps and permits higher acceleration factors for the other undersampled frames than regular SENSE. vSENSE is validated in a phantom, a normal volunteer and eight brain tumor patients at 3 Tesla. RESULTS: vSENSE with an acceleration factor of four generated a 3-6 times smaller error on average than conventional SENSE (P <= 0.02), with acceleration factors of 2-4, as compared with full k-space reconstruction. vSENSE permitted four-fold acceleration for amide proton transfer-weighted images, while regular SENSE could only provide a factor of two. When conventional SENSE is used with vSENSE's variable undersampling pattern, erroneous (~9%) z-spectra result. CONCLUSION: The vSENSE method enabled twice the acceleration and generated more accurate images than conventional SENSE. Magn Reson Med 77:2225-2238, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27364634 TI - [POEMS syndrome as a rare cause of bilateral optic disc edema]. AB - The POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) is a rare paraneoplastic syndrome based on a clonal plasma cell disorder. Optic disc edema (ODE) is a frequent ocular sign in POEMS syndrome. The cause of the ODE has not yet been entirely clarified. This article reports the case of a 62-year-old male suffering from POEMS syndrome with a bilateral ODE. PMID- 27364635 TI - [Sympathetic ophthalmia following repeated pars plana vitrectomy : Clinical findings and spectral domain OCT follow-up]. AB - Sympathetic ophthalmia is a rare form of bilateral granulomatous panuveitis, occurring after penetrating trauma. Hitherto, sympathetic ophthalmia after vitrectomy has only occasionally been described in the literature. This case report presents a female patient with sympathetic ophthalmia after repeated pars plana vitrectomy on the basis of clinical findings and follow-up with fluorescein angiography, spectral domain OCT, and histopathology. PMID- 27364636 TI - [Visual acuity in anti-VEGF therapy for AMD : Can specific characteristics in the SD-OCT help?] AB - BACKGROUND: The efficacy of anti-VEGF therapy in exudative AMD has been established in several large clinical trials using a fixed injection regimen as well as a SD-OCT-based PRN regimen. In these studies, after the first three injections, an increase of the mean visual acuity was observed, which could be stabilized with constant treatment for up to 24 months. However, the specific course of the visual acuity is very different between individuals. The aim of the present study was to correlate specific initial SD-OCT parameters with the course of visual acuity in order to characterize factors that may be important for the individual visual prognosis. PATIENTS AND METHODS: In a prospective case study, the visual course and SD-OCT changes of 156 patients with minimum follow-up of 12 months (mean 80.1 months) were analysed. Visual acuity (LogMar) was investigated at regular intervals and correlated with specific SD-OCT parameters (foveal thickness, height of sub-retinal fluid or presence of associated PED, presence of intra-retinal cysts, length of IS/OS break, choroidal thickness). RESULTS: The initial increase in visual acuity could be stabilized over time. This effect was associated with a decrease in foveal retinal thickness, which also persisted over time. While sub-retinal fluid, presence of PED, and choroidal thickness showed no prognostic relevance for the change in visual acuity, the presence of more advanced central retinal thickness, of intra-retinal cysts or a longer break in the IS/OS junction were associated with a less favourable development of visual acuity. CONCLUSION: In the present study, the presence of more advanced central retinal thickness, of intra-retinal cysts or a larger IS/OS break correlated significantly with a worse visual prognosis. These might be clinical signs for more extensive pre-existing intra-retinal changes. Further analysis and new diagnostic tools may prove this and may result in specific additive neuroprotective or regenerative therapeutic approaches in exudative AMD. PMID- 27364637 TI - [Atrophy of the macula in the context of its wet, age-related degeneration : An inescapable consequence of anti-VEGF therapy?] AB - BACKGROUND: Current understanding of the mechanisms that underlie the long-term consequences of anti-VEGF therapy in wet, age-related macular degeneration (AMD) is poor. Here, the impact of this treatment on the development of macular atrophy (MA) is discussed based on our current pathophysiological understanding. METHODS: This review is based on a PubMed literature survey using the MeSH terms "wet AMD" and "macular atrophy" (151 hits) and limited to publications since 2013 (n = 90). Publications focussing on diagnostics and clinical course not in the context of therapy were excluded. Macular atrophy is defined herein as atrophy affecting the functionally relevant complex of photoreceptors, retinal pigmented epithelium (RPE), Bruch's membrane and choriocapillaris. RESULTS: Experimentally, a primary complete suppression of local VEGF leads to evident changes in the choriocapillaris, whereas its incomplete suppression exacerbates cell death of RPE and photoreceptors. Since pre-existing atrophic changes are already present at diagnosis, the role of anti-VEGF treatment cannot be separated from the spontaneous progression of AMD. The progression of MA appears to be faster under ranibizumab than bevacizumab, and likewise on a monthly rather than as-needed basis. Although MA progresses more rapidly under consequent therapy, visual function remains better. Hence, a functionally relevant progression of atrophy during the first five years of treatment would only be expected in pre-existing advanced MA. CONCLUSIONS: Despite doubts regarding the long-term safety of anti VEGF therapy, it is the author's view that this is the only option to stabilise visual function. The impact of therapy-induced damage on the spontaneous progression of AMD and the biological status of the aging individual cannot be unequivocally assessed. PMID- 27364638 TI - Integrated analysis of gene expression from carbon metabolism, proteome and metabolome, reveals altered primary metabolism in Eucalyptus grandis bark, in response to seasonal variation. AB - BACKGROUND: Seasonal variation is presumed to play an important role in the regulation of tree growth, especially for Eucalyptus grandis, a fast-growing tree. This variation may induce changes in the whole tree at transcriptional, protein and metabolite levels. Bark represents an important group of tissues that protect trees from desiccation and pathogen attack, and it has been identified as potential feedstock for lignocellulosic derived biofuels. Despite the growing interest, little is known about the molecular mechanisms that regulates bark metabolism, particularly in tropical countries. RESULTS: In this study we report the changes observed in the primary metabolism of E. grandis bark during two contrasting seasons in Brazil, summer (wet) and winter (dry), through the combination of transcripts (RT-qPCR), proteome (2-DE gels) and metabolome (GC-MS) analysis, in an integrated manner. Twenty-four genes, involved in carbon metabolism, were analyzed in the two seasons. Eleven were up-regulated in summer, three were up-regulated in winter and ten did not show statistical differences in the expression pattern. The proteomic analysis using 2-DE gels showed 77 proteins expressing differences in abundance, with 38 spots up-regulated in summer and 37 in winter. Different metabolites significantly accumulated during winter. CONCLUSIONS: This study revealed a metabolic reconfiguration in the primary metabolism of E. grandis bark, triggered by seasonal variation. Transcripts and protein data suggests that during winter carbohydrate formation seems to be favored by tree metabolism. Glucose, fructose and sucrose accumulated at significant levels during the winter. PMID- 27364639 TI - Distribution of MEFV gene mutations and R202Q polymorphism in the Serbian population and their influence on oxidative stress and clinical manifestations of inflammation. AB - BACKGROUND: The Mediterranean fever (MEFV) gene codes for protein pyrin, one of the regulators of inflammasome activity in innate immune cells. Mutations in this gene are considered the primary cause of Familial Mediterranean fever, but are also found in other monogenic and multifactorial autoinflammatory diseases. The aim of the study was to determine if healthy carriers of MEFV gene mutations and R202Q polymorphism have clinical manifestations of inflammation and impaired oxidative stress parameters. METHODS: One hundred DNA samples from healthy volunteers (13.3 +/- 8.87 years of age (mean +/- SD); range 2-35) were sequenced by ABI PRISM 310 automated sequencer (PE Applied Biosystems, Norwalk, USA). The Eurofever questionnaire was used to collect retrospectively medical history data. Oxidative stress was determined by measuring spectrophotometrically thiobarbituric acid reactive substances (TBARS) in plasma and erythrocytes, as well as advanced oxidation protein products in plasma. Superoxide dismutase (SOD) activity was determined by McCord and Fridovich method in plasma and erythrocytes, while the catalase erythrocyte activity was assessed using a catalase ELISA kit. RESULTS: We found heterozygous carriers of K695R/N mutations in 5 %, E148Q/N mutations in 6 %, R202Q homozygous polymorphism in 10 % and heterozygous R202Q alterations in 45 % of healthy volunteers. The MEFV mutation carriers and R202Q polymorphism homozygotes reported significantly more often recurrent febrile episodes (p = 0.009), diffuse abdominal pain (p = 0.025), and malaise (p = 0.012) compared to non-carriers. Erythrocyte TBARS levels and plasma SOD activity were higher in persons with MEFV mutations and R202Q/R202Q (p = 0.03 and p = 0.049, respectively). CONCLUSIONS: Healthy individuals may bear E148Q and K695R MEFV gene mutations, as well as R202Q polymorphism in homozygous state. The determined gene alterations contribute to a subtle oxidative stress and may be associated with more frequent episodes of fever and unspecific inflammatory manifestations. An incomplete penetrance or variable expressivity of R202Q in populations of different ethnicity could influence the expression of autoinflammatory diseases phenotype. PMID- 27364640 TI - Final screening round of the NELSON lung cancer screening trial: the effect of a 2.5-year screening interval. AB - BACKGROUND: In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial (NELSON). METHODS: Europe's largest, sufficiently powered randomised lung cancer screening trial was designed to determine whether low-dose CT screening reduces lung cancer mortality by >=25% compared with no screening after 10 years of follow-up. The screening arm (n=7915) received screening at baseline, after 1 year, 2 years and 2.5 years. Performance of the NELSON screening strategy in the final fourth round was evaluated. Comparisons were made between lung cancers detected in the first three rounds, in the final round and during the 2.5-year interval. RESULTS: In round 4, 46 cancers were screen-detected and there were 28 interval cancers between the third and fourth screenings. Compared with the second round screening (1-year interval), in round 4 a higher proportion of stage IIIb/IV cancers (17.3% vs 6.8%, p=0.02) and higher proportions of squamous-cell, bronchoalveolar and small cell carcinomas (p=0.001) were detected. Compared with a 2-year interval, the 2.5 year interval showed a higher non-significant stage distribution (stage IIIb/IV 17.3% vs 5.2%, p=0.10). Additionally, more interval cancers manifested in the 2.5 year interval than in the intervals of previous rounds (28 vs 5 and 28 vs 19). CONCLUSIONS: A 2.5-year interval reduced the effect of screening: the interval cancer rate was higher compared with the 1-year and 2-year intervals, and proportion of advanced disease stage in the final round was higher compared with the previous rounds. TRIAL REGISTRATION NUMBER: ISRCTN63545820. PMID- 27364642 TI - Use existing staff to drive integrated care, says report. PMID- 27364641 TI - Performance of MALDI biotyper compared with VitekTM 2 compact system for fast identification and discrimination of Staphylococcus species isolated from bovine mastitis. AB - : This study was designed to evaluate the ability of MALDI Biotyper (MBT) compared with VitekTM 2 compact system for accurate identification of Staphylococcus aureus (S. aureus) and coagulase-negative staphylococci (CNS) strains and discriminate methicillin-sensitive S. aureus (MSSA) from methicillin resistant S. aureus (MRSA). Throughout Al-Qassim region, Saudi Arabia, a total of 198 isolates of S. aureus (132 MSSA and 66 MRSA) and 44 CNS were collected from five dairy farms where the prevalence of staphylococcal mastitis was reported. The results produced by VitekTM 2 compact system demonstrated that 123/132 MSSA isolates (93.18%), 61/66 MRSA (92.42%), and 37/44 CNS species (84.09%) were correctly identified. However; 130/132 MSSA (98.48%), 64/66 MRSA (96.96%), and 44/44 CNS (100%) were correctly identified by MBT with score >=2. 00. The principal component analysis (PCA) dendrogram generated by MBT illustrated that the tested isolates were classified into two groups of Staphylococcus species at the distance level of 600. S. aureus isolates were found to be closely related with higher peak intensities in the mass of 3,993 Da, 4,121 Da and 5,845 Da were detected in MRSA, whereas, that were lost in MSSA. CONCLUSION: This study verified that MBT is an alternative powerful tool for precise identification and discrimination of Staphylococcus species. PMID- 27364643 TI - Otolith shape lends support to the sensory drive hypothesis in rockfishes. AB - The sensory drive hypothesis proposes that environmental factors affect both signalling dynamics and the evolution of signals and receivers. Sound detection and equilibrium in marine fishes are senses dependent on the sagittae otoliths, whose morphological variability appears intrinsically linked to the environment. The aim of this study was to understand if and which environmental factors could be conditioning the evolution of this sensory structure, therefore lending support to the sensory drive hypothesis. Thus, we analysed the otolith shape of 42 rockfish species (Sebastes spp.) to test the potential associations with the phylogeny, biological (age), ecological (feeding habit and depth distribution) and biogeographical factors. The results showed strong differences in the otolith shapes of some species, noticeably influenced by ecological and biogeographical factors. Moreover, otolith shape was clearly conditioned by phylogeny, but with a strong environmental effect, cautioning about the use of this structure for the systematics of rockfishes or other marine fishes. However, our most relevant finding is that the data supported the sensory drive hypothesis as a force promoting the radiation of the genus Sebastes. This hypothesis holds that adaptive divergence in communication has significant influence relative to other life history traits. It has already been established in Sebastes for visual characters and organs; our results showed that it applies to otolith transformations as well (despite the clear influence of feeding and depth), expanding the scope of the hypothesis to other sensory structures. PMID- 27364644 TI - Antibiotics for treating septic abortion. AB - BACKGROUND: A septic abortion refers to any abortion (spontaneous or induced) complicated by upper genital tract infection including endometritis or parametritis. The mainstay of treatment of septic abortion is antibiotic therapy alone or in combination with evacuation of retained products of conception. Regimens including broad-spectrum antibiotics are routinely recommended for treatment. However, there is no consensus on the most effective antibiotics alone or in combination to treat septic abortion. This review aimed to bridge this gap in knowledge to inform policy and practice. OBJECTIVES: To review the effectiveness of various individual antibiotics or antibiotic regimens in the treatment of septic abortion. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and POPLINE using the following keywords: 'Abortion', 'septic abortion', 'Antibiotics', 'Infected abortion', 'postabortion infection'. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials on 19 April, 2016. SELECTION CRITERIA: We considered for inclusion randomised controlled trials (RCTs) and non-RCTs that compared antibiotic(s) to another antibiotic(s), irrespective of route of administration, dosage, and duration as well as studies comparing antibiotics alone with antibiotics in combination with other interventions such as dilation and curettage (D&C). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from included trials. We resolved disagreements through consultation with a third author. One review author entered extracted data into Review Manager 5.3, and a second review author cross-checked the entry for accuracy. MAIN RESULTS: We included 3 small RCTs involving 233 women that were conducted over 3 decades ago.Clindamycin did not differ significantly from penicillin plus chloramphenicol in reducing fever in all women (mean difference (MD) -12.30, 95% confidence interval (CI) -25.12 to 0.52; women = 77; studies = 1). The evidence for this was of moderate quality. "Response to treatment was evaluated by the patient's 'fever index' expressed in degree-hour and defined as the total quantity of fever under the daily temperature curve with 99 degrees F (37.2 degrees C) as the baseline".There was no difference in duration of hospitalisation between clindamycin and penicillin plus chloramphenicol. The mean duration of hospital stay for women in each group was 5 days (MD 0.00, 95% CI 0.54 to 0.54; women = 77; studies = 1).One study evaluated the effect of penicillin plus chloramphenicol versus cephalothin plus kanamycin before and after D&C. Response to therapy was evaluated by "the time from start of antibiotics until fever lysis and time from D&C until patients become afebrile". Low-quality evidence suggested that the effect of penicillin plus chloramphenicol on fever did not differ from that of cephalothin plus kanamycin (MD -2.30, 95% CI -17.31 to 12.71; women = 56; studies = 1). There was no significant difference between penicillin plus chloramphenicol versus cephalothin plus kanamycin when D&C was performed during antibiotic therapy (MD -1.00, 95% CI -13.84 to 11.84; women = 56; studies = 1). The quality of evidence was low.A study with unclear risk of bias showed that the time for fever resolution (MD -5.03, 95% CI -5.77 to -4.29; women = 100; studies = 1) as well as time for resolution of leukocytosis (MD -4.88, 95% CI -5.98 to -3.78; women = 100; studies = 1) was significantly lower with tetracycline plus enzymes compared with intravenous penicillin G.Treatment failure and adverse events occurred infrequently, and the difference between groups was not statistically significant. AUTHORS' CONCLUSIONS: We found no strong evidence that intravenous clindamycin alone was better than penicillin plus chloramphenicol for treating women with septic abortion. Similarly, available evidence did not suggest that penicillin plus chloramphenicol was better than cephalothin plus kanamycin for the treatment of women with septic abortion. Tetracyline enzyme antibiotic appeared to be more effective than intravenous penicillin G in reducing the time to fever defervescence, but this evidence was provided by only one study at low risk of bias.There is a need for high-quality RCTs providing reliable evidence for treatments of septic abortion with antibiotics that are currently in use. The three included studies were carried out over 30 years ago. There is also a need to include institutions in low-resource settings, such as sub-Saharan Africa, Latin America and the Caribbean, and South Asia, with a high burden of abortion and health systems challenges. PMID- 27364645 TI - Spot urinary 5-hydroxyindoleacetic acid is not an ideal diagnostic test for acute appendicitis. AB - BACKGROUND AND PURPOSE OF THE STUDY: There is growing evidence to suggest the use of urinary 5-hydroxyindoleacetic acid (5-HIAA) test to help with the diagnosis of appendicitis. The aim of our study was to establish whether urinary 5-HIAA could be used as an effective diagnostic test for acute appendicitis. DESIGN AND METHODS: A prospective double-blinded study was carried out from December 2014 to October 2015. Patients admitted to the emergency surgical ward of a teaching hospital with suspected appendicitis were included in the study. The diagnostic accuracy of the test was measured by receiver operating characteristic curve. RESULTS: Ninety-seven patients were divided into 2 groups: acute appendicitis (n=38) and other diagnosis (n=59). The median value of urinary 5-HIAA was 24.19MUmol/L (range, 5.39-138.27) for acute appendicitis vs 18.87MUmol/L (range, 2.27-120.59) for other diagnosis group (P=.038). The sensitivity and specificity of urinary 5-HIAA at a cutoff value of 19MUmol/L were 71% and 50%, respectively. Receiver operating characteristic analysis showed that the area under curve was 0.64 (confidence interval [CI], 0.513-0.737) for urinary 5-HIAA, which was lower than white blood cell count (0.69; CI, 0.574-0.797), neutrophil count (0.68; CI, 0.565-0.792), and C-reactive protein (0.76; CI, 0.657-0.857). There was no significant difference in the median values of 5-HIAA between different grades of severity of appendicitis (P=.704). CONCLUSION: Urinary 5-HIAA is not an ideal test for the diagnosis of acute appendicitis. PMID- 27364646 TI - Serum albumin level is associated with the recurrence of acute ischemic stroke. AB - BACKGROUND: Previous studies have confirmed that low serum albumin levels in acute ischemic stroke patients increased the risk for poor outcome and death, demonstrating the neuroprotective role of albumin. However, there are few studies investigating the relationship between albumin levels and recurrence of stroke. The aim of this study was to evaluate the effect of serum albumin level on the risk of recurrence in patients with acute ischemic stroke. METHODS: Seven hundred fifty-three consecutive patients with acute first-ever ischemic stroke were recruited in this study. Recurrent outcome was measured 1 year after stroke through home interviews (n = 692). RESULTS: Patients with recurrence had significantly lower serum albumin level than those without recurrence (37.07 +/- 4.21 vs 38.91 +/- 3.25). The multiple logistic regression adjustment for confounding factors showed that the association remained significant for patients in the second albumin quartile, the third quartile, and the fourth quartile compared with patients in the first quartile (adjusted odds ratio [aOR] = 0.543, 95% confidence interval [CI]: 0.307-0.959, P= .036; aOR = 0.449, 95% CI: 0.249 0.812, P= .008; and aOR = 0.290, 95% CI: 0.148-0.570, P < .001). CONCLUSION: Lower serum albumin level increases the risk of recurrence in patients with acute ischemic stroke, suggesting that serum albumin level might be used as an indicator for stroke recurrence. PMID- 27364647 TI - Erratum to "Ultrasound-guided nerve blocks for intracapsular and extracapsular hip fractures" [Am J Emerg Med 34(3) (2016), 586-589]. PMID- 27364648 TI - Depression, Type 2 Diabetes, and Poststroke Cognitive Impairment. AB - Background Ten percent of stroke survivors develop dementia, which increases to more than a third after recurrent stroke. Other survivors develop less severe vascular cognitive impairment. In the general population, depression, and diabetes interact in predicting dementia risk, and they are both prevalent in stroke. Objective To assess the cumulative association of comorbid depressive symptoms and type 2 diabetes with cognitive outcomes among stroke survivors. Methods Multicenter observational cohort study of people within 6 months of stroke. Depression and cognitive status were screened using the Center for Epidemiological Studies Depression (CES-D) scale and the Montreal Cognitive Assessment (MoCA), respectively. Processing speed, executive function and memory were assessed using the Trail Making Test parts A and B, and the 5 Word Delayed Free Recall task. Results Among 342 participants (age 67.0 +/- 13.5 years, 43.3% female, 46 +/- 35 days poststroke), the prevalence of type 2 diabetes was 32.2% and depressive symptoms (CES-D >=16) were found in 40.6%. Diabetes and depressive symptoms increased the risk of severe cognitive impairment (MoCA <20) with adjusted odds ratio (OR) 2.12 (95% confidence interval [CI] 1.20-3.74, P = .010) for 1 comorbidity and OR 3.18 (95% CI 1.26-8.02, P = .014) for both comorbidities. Associated cognitive deficits included executive function (F1, 168 = 3.43, P = .035) but not processing speed (F1, 168 = 1.86, P = .16) or memory (F1, 168 = 0.82, P = .44). Conclusions Diabetes and depressive symptoms were associated cumulatively with poorer cognitive screening outcomes poststroke, particularly deficits in executive function. Having 1 comorbidity doubled the odds of screening for severe cognitive impairment, having both tripled the odds. PMID- 27364649 TI - Fungal epidemiology and diversity in cystic fibrosis patients over a 5-year period in a national reference center. AB - The knowledge on prevalence rates of yeasts and moulds in patients with cystic fibrosis (CF) in Germany is scarce. The aim of this report is to give an overview of the diversity and epidemiology of fungal species in CF patients. Over a 5-year period, all fungal isolates cultured from microbiological specimen from CF patients were recorded. Beside standard bacteriological culture media two fungal media were used for cultivation. Species were identified by microscopy, biochemical profiling, MALDI-TOF analysis or DNA sequencing methods. In sum, 25,975 clinical samples from CF patients were analyzed. About 75% of CF patients were colonized by yeasts, mainly Candida albicans (38%) and Candida dubliniensis (12%). In 35% of the patients Aspergillus spp. (Aspergillus fumigatus: 29%) were detected, followed by Exophiala dermatitidis and Scedosporium/Lomentospora complex isolates (4% each). Data for other fungal species are shown. Over a 5 year period, the epidemiology of fungal species detected in CF patients was relatively constant. Clinical microbiology laboratories should carefully monitor samples from CF patients for newly occurring fungal pathogens. PMID- 27364651 TI - Lines of Communication. PMID- 27364650 TI - Molecular characterization of strains of the Trichophyton verrucosum complex from Tunisia. AB - Trichophyton verrucosum is the most frequent etiologic agent of cattle dermatophytosis. Throughout the world, it was the second most common agent of zoophilic dermatophytes in human. The aim of our study was to evaluate the efficacy of the PCR- RFLP and PCR-sequencing methods for the identification and differentiation of T. verrucosum strains.Thirty-six clinical strains identified by morphological characteristics as T. verrucosum were isolated from patients referred to parasitology-mycology laboratory of Sfax University Hospital. Identification of our strains by conventional methods was confirmed by molecular methods in 94.4% of cases. Two strains were reclassified as T. violaceum PCR products digested with HinfI produced three profiles and two patterns with MvaI. Sequence analysis revealed a polymorphism in the ITS1and 5.8S regions. Analysis and alignment of consensus sequences has distinguished two types of genotypes among our T. verrucosum strains. The ITS type I was the dominant genotype (93.7%). Phylogenetic study showed that one cluster comprised T. verrucosum strains with ITS type I and species of T. mentagrophytes complex. It was related to Arthroderma vanbreuseghemii complex. The other cluster contained the two T. verrucosum strains with ITS type II, and was related to Arthroderma benhamiae complex. In this study, most of T. verrucosum isolates were type I, dissimilar to others rare studies where type II has been the most common. Specie and strain differentiation is relevant because it helps in prescribing the correct treatment and determining the source of the infection. PMID- 27364652 TI - Enhancing compassion in general practice: it's not all about the doctor. PMID- 27364653 TI - Are patient relationships the driver for information governance? PMID- 27364654 TI - Who cares for the clinicians? The mental health crisis in the GP workforce. PMID- 27364655 TI - Incidental findings discovered during imaging: implications for general practice. PMID- 27364656 TI - Managing the consequences of cancer in primary care. PMID- 27364657 TI - Child health training: why does the College not act? PMID- 27364658 TI - Proton pump inhibitors may cause elevation in faecal calprotectin levels. PMID- 27364659 TI - Good practice in shared care for inflammatory arthritis. PMID- 27364660 TI - Economies of scale. PMID- 27364661 TI - The Roundhouse model. PMID- 27364663 TI - Correction. PMID- 27364662 TI - Learning disability registers in primary care. PMID- 27364664 TI - Letter from Nepal. PMID- 27364665 TI - General practice: finding a future from the past. PMID- 27364666 TI - QOF's post-mortem. PMID- 27364667 TI - From Balint to square-bashing: 50 years' experience of general practice. PMID- 27364668 TI - Yonder: Workplace violence, childhood obesity, somatoform disorders and 'selfies'. PMID- 27364669 TI - The Kieran Sweeney Prize 2016: a national UK prize for medical writing by GPs. PMID- 27364670 TI - Increasing emotional support for healthcare workers can rebalance clinical detachment and empathy. PMID- 27364671 TI - Books: Hamburgers in Paradise: The Stories Behind the Food We Eat: Fascinating Food. PMID- 27364672 TI - Books: The Diet Myth: The Real Science Behind What We Eat: Cherish Your Germs. PMID- 27364673 TI - Books: The Novel Cure: Books as Therapy. PMID- 27364674 TI - Insight: A Light Bulb Moment: A Light Bulb Moment. PMID- 27364675 TI - BJGP Library: The Little Prince: Escaping into Childhood. PMID- 27364676 TI - Vicious cycle. PMID- 27364677 TI - Bowlby, Balint, and the doctor-patient relationship: towards a theory of human relationships in medical practice. PMID- 27364679 TI - Compassion and the science of kindness: Harvard Davis Lecture 2015. PMID- 27364678 TI - Nappy pad urine samples for investigation and treatment of UTI in young children: the 'DUTY' prospective diagnostic cohort study. AB - BACKGROUND: The added diagnostic utility of nappy pad urine samples and the proportion that are contaminated is unknown. AIM: To develop a clinical prediction rule for the diagnosis of urinary tract infection (UTI) based on sampling using the nappy pad method. DESIGN AND SETTING: Acutely unwell children <5 years presenting to 233 UK primary care sites. METHOD: Logistic regression to identify independent associations of symptoms, signs, and urine dipstick test results with UTI; diagnostic utility quantified as area under the receiver operator curves (AUROC). Nappy pad rule characteristics, AUROC, and contamination, compared with findings from clean-catch samples. RESULTS: Nappy pad samples were obtained from 3205 children (82% aged <2 years; 48% female), culture results were available for 2277 (71.0%) and 30 (1.3%) had a UTI on culture. Female sex, smelly urine, darker urine, and the absence of nappy rash were independently associated with a UTI, with an internally-validated, coefficient model AUROC of 0.81 (0.87 for clean-catch), which increased to 0.87 (0.90 for clean-catch) with the addition of dipstick results. GPs' 'working diagnosis' had an AUROC 0.63 (95% confidence intervals [CI] = 0.53 to 0.72). A total of 12.2% of nappy pad and 1.8% of clean-catch samples were 'frankly contaminated' (risk ratio 6.66; 95% CI = 4.95 to 8.96; P<0.001). CONCLUSION: Nappy pad urine culture results, with features that can be reported by parents and dipstick tests, can be clinically useful, but are less accurate and more often contaminated compared with clean-catch urine culture. PMID- 27364680 TI - Syphilis on the face in primary care: a rare sign of an increasingly common problem. PMID- 27364681 TI - Epigenomic maintenance through dietary intervention can facilitate DNA repair process to slow down the progress of premature aging. AB - DNA damage caused by various sources remains one of the most researched topics in the area of aging and neurodegeneration. Increased DNA damage causes premature aging. Aging is plastic and is characterised by the decline in the ability of a cell/organism to maintain genomic stability. Lifespan can be modulated by various interventions like calorie restriction, a balanced diet of macro and micronutrients or supplementation with nutrients/nutrient formulations such as Amalaki rasayana, docosahexaenoic acid, resveratrol, curcumin, etc. Increased levels of DNA damage in the form of double stranded and single stranded breaks are associated with decreased longevity in animal models like WNIN/Ob obese rats. Erroneous DNA repair can result in accumulation of DNA damage products, which in turn result in premature aging disorders such as Hutchinson-Gilford progeria syndrome. Epigenomic studies of the aging process have opened a completely new arena for research and development of drugs and therapeutic agents. We propose here that agents or interventions that can maintain epigenomic stability and facilitate the DNA repair process can slow down the progress of premature aging, if not completely prevent it. (c) 2016 IUBMB Life, 68(9):717-721, 2016. PMID- 27364682 TI - Stimulated emission of Cooper pairs in a high-temperature cuprate superconductor. AB - The concept of stimulated emission of bosons has played an important role in modern science and technology, and constitutes the working principle for lasers. In a stimulated emission process, an incoming photon enhances the probability that an excited atomic state will transition to a lower energy state and generate a second photon of the same energy. It is expected, but not experimentally shown, that stimulated emission contributes significantly to the zero resistance current in a superconductor by enhancing the probability that scattered Cooper pairs will return to the macroscopically occupied condensate instead of entering any other state. Here, we use time- and angle-resolved photoemission spectroscopy to study the initial rise of the non-equilibrium quasiparticle population in a Bi2Sr2CaCu2O8+delta cuprate superconductor induced by an ultrashort laser pulse. Our finding reveals significantly slower buildup of quasiparticles in the superconducting state than in the normal state. The slower buildup only occurs when the pump pulse is too weak to deplete the superconducting condensate, and for cuts inside the Fermi arc region. We propose this is a manifestation of stimulated recombination of broken Cooper pairs, and signals an important momentum space dichotomy in the formation of Cooper pairs inside and outside the Fermi arc region. PMID- 27364683 TI - Australian general practice nurse's knowledge, attitudes and practices regarding influenza vaccination: a cross-sectional survey. AB - AIMS AND OBJECTIVES: The aim of this study was to examine the knowledge, attitudes and practices of Australian general practice nurses (GPNs) regarding influenza vaccination. BACKGROUND: Despite the evidence for the benefits of influenza vaccination, vaccination rates remain sub-optimal. The knowledge, attitudes and practices of nurses both affects vaccination rates and the advice given to consumers. Given their significant role in opportunistic and planned vaccinations, GPNs are in an optimal position to positively influence vaccination rates. DESIGN: A descriptive cross-sectional survey was used. METHODS: GPNs were recruited by email to complete an online survey. The survey tool comprised the King's College Nurses' Influenza Vaccination Questionnaire and adapted demographic items. Data analysis used descriptive and inferential statistics. Open-ended questions were analysed using thematic analysis. RESULTS: Most of the 85 respondents had received the seasonal influenza vaccination in the last year (n = 67; 78.8%); fewer received the H1N1 vaccination (n = 54; 63.5%). Intention to receive vaccination was affected by previous vaccination. Those who had received the seasonal influenza vaccine in the last year had a higher total knowledge score. The seasonal and total influenza knowledge score was high, with lower scores on the H1N1 sub-scale. A positive correlation was identified between influenza knowledge and risk perception. CONCLUSIONS: This study highlighted the high level of knowledge amongst GPNs related to seasonal influenza, whilst identifying a knowledge deficit around the H1N1 items. It demonstrated that GPN's knowledge of seasonal influenza was related to vaccination status and risk perception. Further research is required to explore how this translates into the advice GPNs give to consumers. RELEVANCE TO CLINICAL PRACTICE: Influenza vaccination should be considered as a key topic for GPNs ongoing professional development. The evidence for links between education and vaccination uptake should encourage employers to facilitate opportunities for this training. Future efforts to increase vaccination uptake in nurses should promote the benefits of vaccination in protecting the individual rather than as a professional responsibility. PMID- 27364684 TI - A high-resolution transcriptome map of cell cycle reveals novel connections between periodic genes and cancer. AB - Progression through the cell cycle is largely dependent on waves of periodic gene expression, and the regulatory networks for these transcriptome dynamics have emerged as critical points of vulnerability in various aspects of tumor biology. Through RNA-sequencing of human cells during two continuous cell cycles (>2.3 billion paired reads), we identified over 1 000 mRNAs, non-coding RNAs and pseudogenes with periodic expression. Periodic transcripts are enriched in functions related to DNA metabolism, mitosis, and DNA damage response, indicating these genes likely represent putative cell cycle regulators. Using our set of periodic genes, we developed a new approach termed "mitotic trait" that can classify primary tumors and normal tissues by their transcriptome similarity to different cell cycle stages. By analyzing >4 000 tumor samples in The Cancer Genome Atlas (TCGA) and other expression data sets, we found that mitotic trait significantly correlates with genetic alterations, tumor subtype and, notably, patient survival. We further defined a core set of 67 genes with robust periodic expression in multiple cell types. Proteins encoded by these genes function as major hubs of protein-protein interaction and are mostly required for cell cycle progression. The core genes also have unique chromatin features including increased levels of CTCF/RAD21 binding and H3K36me3. Loss of these features in uterine and kidney cancers is associated with altered expression of the core 67 genes. Our study suggests new chromatin-associated mechanisms for periodic gene regulation and offers a predictor of cancer patient outcomes. PMID- 27364686 TI - Distribution of IgG galactosylation as a promising biomarker for cancer screening in multiple cancer types. PMID- 27364685 TI - Identification of blood vascular endothelial stem cells by the expression of protein C receptor. AB - Vascular growth and remodeling are dependent on the generation of new endothelial cells from stem cells and the involvement of perivascular cells to maintain vessel integrity and function. The existence and cellular identity of vascular endothelial stem cells (VESCs) remain unclear. The perivascular pericytes in adult tissues are thought to arise from the recruitment and differentiation of mesenchymal progenitors during early development. In this study, we identified Protein C receptor-expressing (Procr+) endothelial cells as VESCs in multiple tissues. Procr+ VESCs exhibit robust clonogenicity in culture, high vessel reconstitution efficiency in transplantation, long-term clonal expansion in lineage tracing, and EndMT characteristics. Moreover, Procr+ VESCs are bipotent, giving rise to de novo formation of endothelial cells and pericytes. This represents a novel origin of pericytes in adult angiogenesis, reshaping our understanding of blood vessel development and homeostatic process. Our study may also provide a more precise therapeutic target to inhibit pathological angiogenesis and tumor growth. PMID- 27364687 TI - Nitrate reduction in sulfate-reducing bacteria. AB - Sulfate-reducing bacteria (SRBs) gain their energy by coupling the oxidation of organic substrate to the reduction of sulfate to sulfide. Several SRBs are able to use alternative terminal electron acceptors to sulfate such as nitrate. Nitrate-reducing SRBs have been isolated from a diverse range of environments. In order to be able to understand the significance of nitrate reduction in SRBs, we need to examine the ecology and physiology of the nitrate-reducing SRB isolates. PMID- 27364688 TI - SOHPRED: a new bioinformatics tool for the characterization and prediction of human S-sulfenylation sites. AB - Protein S-sulfenylation (SOH) is a type of post-translational modification through the oxidation of cysteine thiols to sulfenic acids. It acts as a redox switch to modulate versatile cellular processes and plays important roles in signal transduction, protein folding and enzymatic catalysis. Reversible SOH is also a key component for maintaining redox homeostasis and has been implicated in a variety of human diseases, such as cancer, diabetes, and atherosclerosis, due to redox imbalance. Despite its significance, the in situ trapping of the entire 'sulfenome' remains a major challenge. Yang et al. have recently experimentally identified about 1000 SOH sites, providing an enriched benchmark SOH dataset. In this work, we developed a new ensemble learning tool SOHPRED for identifying protein SOH sites based on the compositions of enriched amino acids and the physicochemical properties of residues surrounding SOH sites. SOHPRED was built based on four complementary predictors, i.e. a naive Bayesian predictor, a random forest predictor and two support vector machine predictors, whose training features are, respectively, amino acid occurrences, physicochemical properties, frequencies of k-spaced amino acid pairs and sequence profiles. Benchmarking experiments on the 5-fold cross validation and independent tests show that SOHPRED achieved AUC values of 0.784 and 0.799, respectively, which outperforms several previously developed tools. As a real application of SOHPRED, we predicted potential SOH sites for 193 S-sulfenylated substrates, which had been experimentally detected through a global sulfenome profiling in living cells, though the actual SOH sites were not determined. The web server of SOHPRED has been made publicly available at for the wider research community. The source codes and the benchmark datasets can be downloaded from the website. PMID- 27364689 TI - Comparison of effect of kangaroo mother care, breastfeeding and swaddling on Bacillus Calmette-Guerin vaccination pain score in healthy term neonates by a clinical trial. AB - BACKGROUND/AIM: The purpose of this research was to compare the analgesic effect of kangaroo mother care (KMC), breastfeeding and swaddling in Bacillus Calmette Guerin (BCG) vaccination in term neonates. METHODS: In a randomized 120 healthy term neonates who received routine BCG vaccination in the first day of their life are distributed into three groups. In group 1, neonates breastfed two minutes before, during and one minute after BCG vaccination. In group 2, neonates received KMC 10 minutes before, during and one minute after vaccination and in group 3, they were swaddled 10 minutes before, during and one minute after vaccination. Primary outcomes included pain score during, one minute and two minutes after BCG vaccination and obtaining pain score of less than three during vaccination . RESULTS: Pain scores during, one minute and two minutes after vaccination in group 1 were lower than in groups 2 and 3. Group 1 had higher success rate in painless vaccination and had lower crying duration in comparison to another groups (p < 0.05) Conclusion: Breastfeeding was more effective than KMC and swaddling in reduction of BCG vaccination pain in healthy term neonates. PMID- 27364691 TI - Medical marijuana and pain management. PMID- 27364690 TI - Intracellular signalling pathways: targets to reverse immunosenescence. AB - Ageing is a very complex process, the result of the dysregulation of multiple systems interacting in many ways. A prominent change occurring with ageing is related to the architecture and functioning of the immune system, viewed commonly as detrimental and termed 'immunosenescence'. However, age-associated changes may also lead to increased function in certain respects, which can be viewed as adaptive. None the less, on balance it is well-recognized that immunosenescence is accompanied by the low-grade inflammation observed commonly in elderly people, which has been dubbed 'inflamm-ageing'. The exact cause and significance of all these changes is not clear, but there is a consensus that they are related to the occurrence of chronic non-infectious age-associated disease, as well as increased susceptibility to infections. Alterations to immune cell signalling may be a prominent cause of malfunctioning immunity. Emerging attempts to reverse immunosenescence have recently targeted the signalling pathways in various different cell types of the immune system. Here, we review and discuss alterations in the signalling pathways of immune cells with ageing and consider current targets and means to modulate altered functions. We discuss the potential dangers as well as the benefits of these interventions, and consider future approaches to this problem. PMID- 27364692 TI - Lick of death: Capnocytophaga canimorsus is an important cause of sepsis in the elderly. AB - A 70-year-old Caucasian woman was treated for Capnocytophaga canimorsus septicaemia. The source of bacteraemia was very likely to be her household pet, an Italian greyhound. The patient presented with a presumed complex partial seizure but deteriorated rapidly with sepsis and multiorgan dysfunction. Neither scratch nor bite was established, although close petting including licks was reported. Blood cultures grew Gram-negative rods, identified by molecular techniques as C. canimorsus-a bacterium frequently isolated in the oral cavities of dogs and cats. A full recovery was made following 2 weeks of intensive care support and broad-spectrum antibiotics. No underlying immune dysfunction was found. PMID- 27364694 TI - Mean diffusivity of basal ganglia and thalamus specifically associated with motivational states among mood states. AB - Previously, we proposed that the mean diffusivity (MD), a measure of diffusion tensor imaging (DTI) in areas of the dopaminergic system (MDDS), is associated with motivation. In this study, we tested if and how the motivational state is associated with MD in comparison with other mood states. We also tested the associations of these mood states with multiple cognitive functions. We examined these issues in 766 right-handed healthy young adults. We employed analyses of MD and a psychological measure of the profile of mood states (POMS) as well as multiple cognitive functions. We detected associations between the higher Vigor subscale of POMS and lower MD in the right globus pallidum, right putamen to right posterior insula, right caudate body, and right thalamus, and these associations were highly specific to the Vigor subscale. Similarly, the association of the motivational state with creativity measured by divergent thinking (CMDT) was rather specific and prominent compared with that of the other mood states and cognitive functions. In conclusion, when affective states are finely divided, only the motivational state is associated with MD in the areas related to the dopaminergic system, and psychological mechanisms that had been associated with dopaminergic system (CMDT). These results suggest that these mechanisms specifically contribute to the motivational state and not to the other states, such as depression and anxiety. PMID- 27364693 TI - Enforced DNA repair enzymes rescue neurons from apoptosis induced by target deprivation and axotomy in mouse models of neurodegeneration. AB - It is unknown whether DNA damage accumulation is an upstream instigator or secondary effect of the cell death process in different populations of adult postmitotic neurons in the central nervous system. In two different mouse models of injury-induced neurodegeneration characterized by relatively synchronous accumulation of mitochondria, oxidative stress, and DNA damage prior to neuronal apoptosis, we enforced the expression of human 8-oxoguanine DNA glycosylase (hOGG1) and human apurinic-apyrimidinic endonuclease-1/Ref1 (hAPE) using recombinant adenoviruses (Ad). Thalamic lateral geniculate neurons and lumbar spinal cord motor neurons were transduced by Ad-hOGG1 and Ad-hAPE injections into the occipital cortex and skeletal muscle, respectively, prior to their target deprivation- and axotomy-induced retrograde apoptosis. Enforced expression of hOGG1 and hAPE in thalamus and spinal cord was confirmed by western blotting and immunohistochemistry. In injured populations of neurons in thalamus and spinal cord, a DNA damage response (DDR) was registered, as shown by localization of phospho-activated p53, Rad17, and replication protein A-32 immunoreactivities, and this DDR was attenuated more effectively by enforced hAPE expression than by hOGG1 expression. Enforced expression of hOGG1 and hAPE significantly protected thalamic neurons and motor neurons from retrograde apoptosis induced by target deprivation and axotomy. We conclude that a DDR response is engaged pre apoptotically in different types of injured mature CNS neurons and that DNA repair enzymes can regulate the survival of retrogradely dying neurons, suggesting that DNA damage and activation of DDR are upstream mechanisms for this form of adult neurodegeneration in vivo, thus identifying DNA repair as a therapeutic target for neuroprotection. PMID- 27364695 TI - Multiparametric evaluation of preoperative MRI in early stage breast cancer: prognostic impact of peri-tumoral fat. AB - PURPOSE: Obesity is associated with adverse outcomes in breast cancer patients. Fat-specific cytokines (adipokines) have been proposed as key drivers of breast cancer progression, invasion, and metastasis. We aimed at assessing correlations between peri-tumoral fat, quantified on magnetic resonance imaging (MRI) and pathologic factors potentially impacting therapy recommendations. METHODS: We retrospectively reviewed records of 63 patients with early stage breast cancer who underwent preoperative MRI imaging using appropriately weighted series for breast and tumor contouring. Fat volumes were generated through voxel intensity filtering. The peri-tumoral region was defined as the intersection of a 1-cm spherical extension around the tumor and the breast contour. Peri-tumoral fat was defined as the fraction of a fat content in this volume. Surgical pathology records were used to extract clinical data. Statistical analyses were conducted using Pearson and Spearman correlation coefficients. RESULTS: Among reviewed patients, 45 had T1 tumors (1.22 +/- 0.85 cm diameter) and 18 had T2 tumors (2.08 +/- 1.06 cm). Axillary lymph nodes were dissected in 31 and positive in 17 patients analyzed. Peri-tumoral fat ratio ranged between 25 and 99 %. Peri tumoral fat ratio significantly correlated with the nodal-positive ratio of positive axillary lymph nodes (r = 0.532). Peri-tumoral fat ratio demonstrated optimally prominent correlation among obese patients upon body mass index categorical stratification. CONCLUSIONS: In women with early stage breast cancer, peri-tumoral fat correlates positively with the ratio of pathologically involved axillary nodes. This work highlights a novel method for quantitating peri-tumoral fat content. Preoperative breast MRI may be utilized to predict extent of axillary disease. PMID- 27364696 TI - Ulinastatin to prevent acute kidney injury after cardiopulmonary bypass surgery: does serum creatinine tell the whole story? PMID- 27364697 TI - Interference of alpha-Synuclein Uptake by Monomeric beta-Amyloid1-40 and Potential Core Acting Site of the Interference. AB - Increasing evidence suggests an important role of alpha-synuclein (alpha-Syn) in the pathogenesis of Parkinson's disease (PD). The inter-neuronal spread of alpha Syn via exocytosis and endocytosis has been proposed as an explanation for the neuropathological findings of PD in sub-clinical and clinical phases. Therefore, interfering the uptake of alpha-Syn by neurons may be an important step in slowing or modifying the propagation of the disease. The purposes of our study were to investigate if the uptake of alpha-Syn fibrils can be specifically interfered with monomeric beta-Amyloid1-40 (Abeta40) and to characterise the core acting site of interference. Using a radioisotope-labelled uptake assay, we found an 80 % uptake reduction of alpha-Syn fibrils in neurons interfered with monomeric Abeta40, but not beta-Amyloid1-42 (Abeta42) as compared to controls. This finding was further confirmed by enzyme-linked immunosorbent assay (ELISA) with alpha-Syn uptake reduced from about 80 % (Abeta42) to about 20 % (Abeta40) relative to controls. To define the region of Abeta40 peptide capable of the interference, we explored shorter peptides with less amino acid residues from both the C-terminus and N-terminus. We found that the interference effect was preserved if amino acid residue was trimmed to position 11 (from N-terminus) and 36 (from C-terminus), but dropped off significantly if residues were trimmed beyond these positions. We therefore deduced that the "core acting site" lies between amino acid residue positions 12-36. These findings suggest alpha-Syn uptake can be interfered with monomeric Abeta40 and that the core acting site of interference might lie between amino acid residue positions 12-36. PMID- 27364699 TI - AMSIG annual scientific meeting - Sydney April 30 2016. PMID- 27364700 TI - Gene regulation at a distance: From remote enhancers to 3D regulatory ensembles. AB - Large-scale identification of elements associated with gene expression revealed that many of them are located extremely far from gene transcriptional start sites. We review here the growing evidence that show that distal cis-acting elements provide key instructions to genes, as genetic variation affecting them is growingly identified as an importance source of phenotypic diversity and disease. We discuss the different mechanisms that allow these elements to exert their regulatory functions, in a robust and specific manner, despite the large genomic distances separating them from their target genes. We particularly focus on the role of the structural organization of the genome in guiding such regulatory interactions. PMID- 27364701 TI - Mefloquine and its oxazolidine derivative compound are active against drug resistant Mycobacterium tuberculosis strains and in a murine model of tuberculosis infection. AB - Repurposing of drugs to treat tuberculosis (TB) has been considered an alternative to overcome the global TB epidemic, especially to combat drug resistant forms of the disease. Mefloquine has been reported as a potent drug to kill drug-resistant strains of Mycobacterium tuberculosis. In addition, mefloquine-derived molecules have been synthesised and their effectiveness against mycobacteria has been assessed. In this work, we demonstrate for the first time the activities of mefloquine and its oxazolidine derivative compound 1E in a murine model of TB infection following administration of both drugs by the oral route. The effects of associations between mefloquine or 1E with the clinically used antituberculosis drugs isoniazid, rifampicin, ethambutol, moxifloxacin and streptomycin were also investigated. Importantly, combination of mefloquine with isoniazid and of 1E with streptomycin showed a two-fold decrease in their minimum inhibitory concentrations (MICs). Moreover, no tested combinations demonstrated antagonist interactions. Here we describe novel evidence on the activity of mefloquine and 1E against a series of quinolone resistant M. tuberculosis strains. These data show MICs against quinolone resistant strains (0.5-8 ug/mL) similar to or lower than those previously reported for multidrug-resistant strains. Taking these results together, we can suggest the use of mefloquine or 1E in combination with clinically available drugs, especially in the case of resistant forms of TB. PMID- 27364702 TI - Tropical Medicine & International Health. PMID- 27364698 TI - Neurotoxicity in the Post-HAART Era: Caution for the Antiretroviral Therapeutics. AB - Despite the advent of highly active antiretroviral therapy (HAART), HIV associated neurological disorders (HAND) remain a major challenge in human immunodeficiency virus (HIV) treatment. The early implementation of HAART in the infected individuals helps suppress the viral replication in the plasma and other compartments. Several studies also report the beneficial effect of drugs that successfully penetrate central nervous system (CNS). However, recent data in both clinical setup and in in vitro studies indicate CNS toxicity of the antiretrovirals (ARVs). Although the evidence is limited, correlation between prolonged use of ARVs and neurotoxicity strongly suggests that it is essential to study the underlying mechanisms responsible for such toxicity. Furthermore, closer attention toward clinical outcomes is required to screen various ARV regimens for their association with HAND and other comorbidities. A growing body of literature also indicates a possible role of accelerated aging in the antiretroviral therapy-associated neurotoxicity. Lastly, owing to high pill burden, multiple drugs in the HIV treatment also invite a possible role of drug drug interaction via various cytochrome P450 enzymes. The particular emphasis of this review is to highlight the need to identify alternative approaches in reducing the CNS toxicity of the ARV drugs in HIV-infected individuals. PMID- 27364703 TI - Image Quality Ranking Method for Microscopy. AB - Automated analysis of microscope images is necessitated by the increased need for high-resolution follow up of events in time. Manually finding the right images to be analyzed, or eliminated from data analysis are common day-to-day problems in microscopy research today, and the constantly growing size of image datasets does not help the matter. We propose a simple method and a software tool for sorting images within a dataset, according to their relative quality. We demonstrate the applicability of our method in finding good quality images in a STED microscope sample preparation optimization image dataset. The results are validated by comparisons to subjective opinion scores, as well as five state-of-the-art blind image quality assessment methods. We also show how our method can be applied to eliminate useless out-of-focus images in a High-Content-Screening experiment. We further evaluate the ability of our image quality ranking method to detect out-of focus images, by extensive simulations, and by comparing its performance against previously published, well-established microscopy autofocus metrics. PMID- 27364704 TI - Questionable oncologic benefits of degarelix. AB - INTRODUCTION: Luteinizing hormone releasing hormone (LhRh) antagonist degarelix has been approved by the Food and Drug Administration (FDA) for the treatment of advanced prostate cancer in 2008. However, the studies that followed such initial approval have several limitations. OBJECTIVE: To make a critical review of those publications. METHODS: Literature search on degarelix. RESULTS: The studies supporting the use of degarelix are criticized on the basis of selection bias in regards to the heterogeneous populations described, ad hoc analyses with low statistical merit, and the presentation of selected data that would appear to be favorable to the evaluated medication. In addition, those studies still have not shown that any of the data that they point out have any association with clinical benefit. CONCLUSION: The flawed methodology of these publications makes the evidence to support the use of degarelix rather weak. PMID- 27364705 TI - What is the malignant potential of clear cell papillary renal cell carcinoma? PMID- 27364706 TI - [Analysis of cerebrovascular disease mortality in Costa Rica between the years 1920-2009]. AB - OBJECTIVE: To analyze the trend in mortality from cerebrovascular diseases in Costa Rica and its impact on overall mortality from 1920 to 2009. METHODS: Crude rates by triennium and quinquennium were obtained. We also obtanied age standardized rates in the age group 35-74 years during the period 1970-2009. Finally we got the death percentage from stroke in relation to overall mortality. RESULTS: The trend for the period 1920-1969 was to the upside (r=0.82, r2=0.67, betha 0.30; P<=0.00) whereas for the period 1970 occurred otherwise (r=0.42, r2=0.18, betha -0064; P=0.01). Adjusted for the group 35-74 years between 1970 2009 rates decreased by 58.03% was statistically significant trend for both sexes; men r2=0.94, betha: -0.73; women: r2=0.97, betha: 0.95. The maximum percentage of mortality from stroke in relation to the overall mortality was 7.22 in the period 1985-1989 reached down to 5.92% in 2005-2009. CONCLUSIONS: In the Latin American context, stroke mortality rates in Costa Rica are low but still represent a serious public health problem by the high mortality, morbidity and disability that they cause, despite a downward trend. PMID- 27364707 TI - [Prosthetic heart valve thrombosis treated with slow infusion fibrinolytic therapy in patient with acute isquemic stroke]. PMID- 27364708 TI - [Septic paradoxical pulmonary embolisms in a patient with aortic valve endocarditis and interventricular communication: the backdoor]. PMID- 27364725 TI - Postoperative Gastroesophageal Reflux After Laparoscopic Heller-Dor for Achalasia: True Incidence with an Objective Evaluation. AB - INTRODUCTION: The most common complication after laparoscopic Heller-Dor (LHD) is gastroesophageal reflux disease (GERD). The present study aimed (a) to analyze the true incidence of postoperative reflux by objectively assessing a large group of LHD patients and (b) to see whether the presence of typical GERD symptoms correlates with the real incidence of postoperative reflux. METHODS: After LHD, patients were assessed by means of a symptom score, endoscopy, esophageal manometry, and 24-h pH monitoring. Patients were assigned to three groups: those did not accept to perform 24-h pH monitoring (group NP); those with normal postoperative pH findings (group A); and those with pathological postoperative acid exposure (group B). RESULTS: Four hundred sixty-three of the 806 LHD patients agreed to undergo follow-up 24-h pH monitoring. Normal pH findings were seen in 423 patients (group A, 91.4 %), while 40 (8.6 %) had a pathological acid exposure (group B). The median symptom scores were similar: 3.0 (IQR 0-8) in group A and 6.0 (IQR 0-10) in group B (p = 0.29). At endoscopy, the percentage of esophagitis was also similar (11 % in group A, 19 % in group B; p = 0.28). CONCLUSIONS: This study demonstrated that, after LHD was performed by experienced surgeons, the true incidence of postoperative GERD is very low. The incidence of this possible complication should be assessed by pH monitoring because endoscopic findings and symptoms may be misleading. PMID- 27364726 TI - Morbidity and Mortality After Gastrectomy: Identification of Modifiable Risk Factors. AB - BACKGROUND: Morbidity after gastrectomy remains high. The potentially modifiable risk factors have not been well described. This study considers a series of potentially modifiable patient-specific and perioperative characteristics that could be considered to reduce morbidity and mortality after gastrectomy. METHODS: This retrospective cohort study includes adults in the ACS NSQIP PUF dataset who underwent gastrectomy between 2011 and 2013. Sequential multivariable models were used to estimate effects of clinical covariates on study outcomes including morbidity, mortality, readmission, and reoperation. RESULTS: Three thousand six hundred and seventy-eight patients underwent gastrectomy. A majority of patients had distal gastrectomy (N = 2,799, 76.1 %) and had resection for malignancy (N = 2,316, 63.0 %). Seven hundred and ninety-eight patients (21.7 %) experienced a major complication. Reoperation was required in 290 patients (7.9 %). Thirty-day mortality was 5.2 %. Age (OR = 1.01, 95 % CI = 1.01-1.02, p = 0.001), preoperative malnutrition (OR = 1.65, 95 % CI = 1.35-2.02, p < 0.001), total gastrectomy (OR = 1.63, 95 % CI = 1.31-2.03, p < 0.001), benign indication for resection (OR = 1.60, 95 % CI = 1.29-1.97, p < 0.001), blood transfusion (OR = 2.57, 95 % CI = 2.10-3.13, p < 0.001), and intraoperative placement of a feeding tubes (OR = 1.28, 95 % CI = 1.00-1.62, p = 0.047) were independently associated with increased risk of morbidity. Association between tobacco use and morbidity was statistically marginal (OR = 1.23, 95 % CI = 0.99-1.53, p = 0.064). All-cause postoperative morbidity had significant associations with reoperation, readmission, and mortality (all p < 0.001). CONCLUSIONS: Mitigation of perioperative risk factors including smoking and malnutrition as well as identified operative considerations may improve outcomes after gastrectomy. Postoperative morbidity has the strongest association with other measures of poor outcome: reoperation, readmission, and mortality. PMID- 27364728 TI - A five years study of antiviral effect of entecavir in Chinese chronic hepatitis B patients. AB - Entecavir (ETV) is a potent viral replication inhibitor for chronic hepatitis B (CHB) patients. To investigate the efficacy of ETV in Chinese nucleos(t)ide(NA) experienced CHB patients. Among 89 CHB patients with ETV monotherapy for >=6 months, 33/89 (37%) or 56/89 (73%) were NA-naive or NA-experienced. During a median follow-up of 5.75 years, all NA-naive CHB patients achieved VR without genotypic ETV-resistance. However, VR was observed in 50/56 (~90%) of NA experienced CHB patients during a median follow-up of 4.75 years. Antiviral efficacy was not reduced in patients with previous lamivudine (LAM) with/without LAM-resistance (HR 0.465; 95% CI 0.196-1.100; p > 0.05) (HR 0.472; 95% CI 0.205 1.091; p > 0.05). Patients with a primary treatment failure to adefovir (ADV) had a reduced probability of achieving VR compared to NA-naive (HR 0.496; 95% CI 0.287-0.857; p < 0.01). Previous ADV-experienced patients with a partial VR (HR 1.253; 95% CI 0.429-3.665; p > 0.05) did not influence antiviral response to ETV. The antiviral efficacy of ETV is not influenced by previous treatment LAM with/without LAM-resistance. ETV may still be an option in ADV-experienced patients with a partial VR, but not advised in patients with a primary treatment failure to ADV. PMID- 27364729 TI - Recreational scuba diving in patients with congenital heart disease: Time for new guidelines. AB - The number of recreational scuba divers is steadily increasing. In its latest recommendations, the French Federation of Undersea Studies and Sports listed congenital heart disease as a formal and final contraindication to scuba diving. On the other hand, with the progress made in their management, the prognosis and quality of life of patients with congenital heart diseases have improved considerably, enabling them to engage in physical and sports endeavours, which are known to confer general health and psychological benefits. As a consequence, the ability of these patients to dive has become a regular and recurrent issue. We review the various types of scuba diving, the physical performance required for its practice, its effects on cardiovascular function and the elements that need to be considered before recommending whether it can be practiced safely at various levels of difficulty. Because of the diversity and broad heterogeneity of congenital heart diseases, a detailed evaluation of each patient's performance based on clinical criteria common to all congenital heart diseases is recommended. PMID- 27364727 TI - [Multiparametric and molecular imaging of breast tumors with MRI and PET/MRI]. AB - CLINICAL/METHODICAL ISSUE: Magnetic resonance imaging (MRI) of the breast is an indispensable tool in breast imaging for many indications. Several functional parameters with MRI and positron emission tomography (PET) have been assessed for imaging of breast tumors and their combined application is defined as multiparametric imaging. Available data suggest that multiparametric imaging using different functional MRI and PET parameters can provide detailed information about the hallmarks of cancer and may provide additional specificity. STANDARD RADIOLOGICAL METHODS: Multiparametric and molecular imaging of the breast comprises established MRI parameters, such as dynamic contrast-enhanced MRI, diffusion-weighted imaging (DWI), MR proton spectroscopy ((1)H-MRSI) as well as combinations of radiological and MRI techniques (e. g. PET/CT and PET/MRI) using radiotracers, such as fluorodeoxyglucose (FDG). METHODICAL INNOVATIONS: Multiparametric and molecular imaging of the breast can be performed at different field-strengths (range 1.5-7 T). Emerging parameters comprise novel promising techniques, such as sodium imaging ((23)Na MRI), phosphorus spectroscopy ((31)P MRSI), chemical exchange saturation transfer (CEST) imaging, blood oxygen level dependent (BOLD) and hyperpolarized MRI as well as various specific radiotracers. ACHIEVEMENTS: Multiparametric and molecular imaging has multiple applications in breast imaging. Multiparametric and molecular imaging of the breast is an evolving field that will enable improved detection, characterization, staging and monitoring for personalized medicine in breast cancer. PMID- 27364730 TI - Visible-Light-Promoted Direct Amination of Phenols via Oxidative Cross Dehydrogenative Coupling Reaction. AB - A transition-metal-free approach was disclosed for intermolecular aryl C-N bonds formation between phenols and cyclic anilines via cross-dehydrogenative coupling (CDC) amination that was mediated by visible light, wherein K2S2O8 served as an external oxidant. The salient features of this protocol include circumventing the requirement for prefunctionalized starting materials and achieving single regioselectivity of amination adducts at room temperature. PMID- 27364732 TI - New Preparative Approaches for Micro and Nano Drug Delivery Carriers. AB - The full success of pharmacological therapies is strongly depending on the use of suitable, efficient and smart drug delivery systems (DDSs). Thus DDSs development is one of the main challenges in pharmaceutical industry both to achieve tailored carrier systems based on drug features and to promote manufacturing innovations to reduce energetic resources, emissions, wastes and risks. Main functions of an ideal DDS are: to protect loaded active molecules from degradation in physiological environments; to deliver them in a controlled manner and towards specific organs or tissues, to allow the maintenance of drug concentration within therapeutic window. Smart features, such as those able to induce active molecule release upon the occurrence of specific physiological stimuli, are also desirable. Under the manufacturing point of view, the current industrial scenery is obliged to respond to the increasing market requirements and to the mandatory rules in sustainable productions such as raw material and energy savings. In this work a general framework on drug delivery systems preparation techniques is presented. In particular two sections on innovation in preparative approaches carried out are detailed. These latter involve the use of microwave and ultrasonic energy applied in the production of polymeric and lipidic delivery systems on micro- and nanometric scale. The novelties of these preparative approaches are emphasized and examples of developed drug delivery carriers, loaded with vitamins and drug mimicking siRNA, are shown. PMID- 27364731 TI - Single-Cell Transcriptomics of the Human Endocrine Pancreas. AB - Human pancreatic islets consist of multiple endocrine cell types. To facilitate the detection of rare cellular states and uncover population heterogeneity, we performed single-cell RNA sequencing (RNA-seq) on islets from multiple deceased organ donors, including children, healthy adults, and individuals with type 1 or type 2 diabetes. We developed a robust computational biology framework for cell type annotation. Using this framework, we show that alpha- and beta-cells from children exhibit less well-defined gene signatures than those in adults. Remarkably, alpha- and beta-cells from donors with type 2 diabetes have expression profiles with features seen in children, indicating a partial dedifferentiation process. We also examined a naturally proliferating alpha-cell from a healthy adult, for which pathway analysis indicated activation of the cell cycle and repression of checkpoint control pathways. Importantly, this replicating alpha-cell exhibited activated Sonic hedgehog signaling, a pathway not previously known to contribute to human alpha-cell proliferation. Our study highlights the power of single-cell RNA-seq and provides a stepping stone for future explorations of cellular heterogeneity in pancreatic endocrine cells. PMID- 27364733 TI - In vivo EPR extracellular pH-metry in tumors using a triphosphonated trityl radical. AB - PURPOSE: The ability to assess the extracellular pH (pHe) is an important issue in oncology, because extracellular acidification is associated with tumor aggressiveness and resistance to cytotoxic therapies. In this study, a stable triphosphonated triarylmethyl (TPTAM) radical was qualified as a pHe electron paramagnetic resonance (EPR) molecular reporter. METHODS: Calibration of hyperfine splitting as a function of pH was performed using a 1.2-GHz EPR spectrometer. Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) was used as an extracellular paramagnetic broadening agent to assess the localization of TPTAM when incubated with cells. In vivo EPR pH-metry was performed in MDA, SiHa, and TLT tumor models and in muscle. Bicarbonate therapy was used to modulate the tumor pHe. EPR measurements were compared with microelectrode readouts. RESULTS: The hyperfine splitting of TPTAM was strongly pH-dependent around the pKa of the probe (pKa = 6.99). Experiments with Gd-DTPA demonstrated that TPTAM remained in the extracellular compartment. pHe was found to be more acidic in the MDA, SiHa, and TLT tumor models compared with muscle. Treatment of animals by bicarbonate induced an increase in pHe in tumors: similar variations in pHe were found when using in vivo EPR or invasive microelectrodes measurements. CONCLUSION: This study demonstrates the potential usefulness of TPTAM for monitoring pHe in tumors. Magn Reson Med 77:2438-2443, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27364734 TI - Endovascular Treatment of Thoracoabdominal Aorta Aneurysm by the Combination of a Stent Graft with Multiple Overlapping Bare Stents. AB - A 41-year-old male diagnosed with Crawford III thoracoabdominal aorta aneurysm (TAAA) was treated using a completely endovascular approach. After the combined implementation of 4 overlapping bare stents and a stent graft, TAAA was excluded while the 4 visceral arteries were reserved. Follow-up computed tomography scans at 3 and 6 months showed that the aneurysm had almost disappeared, while the vital branches remained open. This case may provide an acceptable alternative choice for treating TAAA in selected patients. PMID- 27364735 TI - Extending Abdominal Aortic Aneurysm Detection to Older Age Groups: Preliminary Results from the Liege Screening Programme. AB - BACKGROUND: There is evident benefit in terms of reduced aneurysm-related mortality from screening programs of abdominal aortic aneurysm (AAA) in men aged 65 years and more. Recent studies in the United Kingdom and Sweden have shown a decline of the prevalence of AAA in the general population. Current screening policies (e.g., men aged 65-74 years), however, do not account for aging and increased life expectancy of Western populations. This study investigated AAA detection by extending the target population to older age groups (75-85 years). METHODS: AAA screening was conducted in the County of Chaudfontaine (Liege, Belgium) on the population of elderly (n = 3,054). The participation rate was 36%. The 1,101 participants (722 men aged 65-85 years and 379 women aged 74-85 years) were examined by ultrasound scan. AAA was defined as an infrarenal aortic outer-outer diameter of at least 3 cm. Demographics, clinical parameters, and risk factors were also recorded. AAA prevalence was estimated, and patients with and without AAA were compared by logistic regression. RESULTS: The overall AAA prevalence was 3.6% (n = 40). In female participants, AAA prevalence was low (1.3%). In men, it amounted 2.7% in the 65-74 age group but rose to 7.3% in the age-extended group (75-85 years). Further in addition to age, height, current smoking, history of coronary artery disease, hypercholesterolemia, peripheral artery disease of the lower limbs, and varicose veins were significantly associated with the presence of AAA. CONCLUSIONS: These preliminary findings, based on a representative sample of the elderly population of the Liege region, support the idea that current AAA screening policies should be updated to cover an increasingly aging population. The presence of varicose veins as a potential risk factor for AAA should also be considered during screening. PMID- 27364736 TI - Open Versus Endovascular Treatment for Patients with Post-Carotid Endarterectomy Restenosis: Early and Long-term Results. AB - BACKGROUND: The aim of this study is to assess and compare the short- and long term results of carotid artery stenting (CAS) and redo surgery in patients with restenosis after carotid endarterectomy (CEA). METHODS: From January 1988 to December 2014, 44 consecutive patients were treated for carotid restenosis (CR): 23 redo-CEA (52.3%) and 21 CAS (47.7%). Data from these patients were prospectively collected in a dedicated database. Early results and 3-year end points were analyzed and compared between groups with chi2 test, Kaplan-Meier curves, and Breslow test. RESULTS: Demographic characteristics and comorbidity were similar in both groups, except for arterial hypertension and chronic renal insufficiency which were higher in the CAS group. CR was symptomatic in 7 patients in the redo-CEA group (30.4%) and 1 (4.8%) in CAS (P = 0.04). No differences were found in the time period between primary CEA and reintervention, critical carotid stenosis, or contralateral carotid occlusion. Median follow-up was 61.5 months. In the redo-CEA group, 1 patient (4.3%) had a perioperative transient ischemic attack and 3 (13%) experienced cranial nerve injury with complete regression at 30 days. No differences were found between groups in terms of early and long-term mortality, neurologic morbidity, and overall morbidity. The rate of secondary restenosis and freedom from reintervention was similar in both groups during follow-up. CONCLUSIONS: Both CAS and redo-CEA are suitable options for patients with CR. CAS might be the treatment of choice due to the risk of cranial nerve injuries in redo-CEA. When CAS is contraindicated, redo-CEA remains a safe and effective treatment option. PMID- 27364737 TI - Treatment of Infected Aneurysms of the Abdominal Aorta and Iliac Artery with Endovascular Aneurysm Repair and Percutaneous Drainage. AB - Infected aneurysm remains one of the most challenging diseases for vascular surgeons. We describe the successful treatment of 2 cases of infected aneurysms with endovascular aneurysm repair and percutaneous computed tomography-guided drainage. This strategy may be an effective alternative to open surgical repair in selected patients. PMID- 27364738 TI - The Influence of Neurodevelopmental Treatment on Transforming Growth Factor-beta1 Levels and Neurological Remodeling in Children With Cerebral Palsy. AB - Neurodevelopmental treatment is an advanced therapeutic approach for the neural rehabilitation of children with cerebral palsy. Cerebral palsy represents a spectrum of neurological disorders primarily affecting gross motor function. The authors investigated the effects of neurodevelopmental treatment on serum levels of transforming growth factor-beta1 (TGF-beta1), a neuroprotective cytokine, and improvements to motor skills. Serum TGF-beta1 levels and total score of the Gross Motor Function Measure-88 (GMFM-88) were significantly higher in children with cerebral palsy who underwent neurodevelopmental treatment compared to untreated patients (P < .01). Furthermore, the improved GMFM-88 total scores after neurodevelopmental treatment were significantly higher in children under the age of 3 with cerebral palsy than in older patients (P < .01). The authors demonstrate that the integration of TGF-beta1 levels and GMFM-88 total score could be used to assess the efficacy of neurodevelopmental treatment. Moreover, the findings provide further scientific support for the early intervention and neurological rehabilitation of young children with cerebral palsy. PMID- 27364739 TI - Differences in Metabolite Concentrations Between the Hemispheres of the Brain in Healthy Children: A Proton Magnetic Resonance Spectroscopy Study (1HMRS). AB - The aim of this (1)HMRS study was to identify hemispheric asymmetries in metabolismus in healthy children. The study group consisted of children of both sexes aged 6 to 15. Concentrations of 6 metabolites occurring in the brain were determined for 6 locations: hippocampus, frontal lobe, and basal ganglia in the left and right hemispheres. There were no hemispheric differences in the metabolites' concentrations in the brain in children when the variable of sex was disregarded. Only in the group of boys and in the group of girls did the findings show few discrepancies. In none of these groups, relative concentrations to creatine concentration were found to be significantly different between hemispheres. In clinical practice, concentrations of specific metabolites are most frequently determined relative to the concentration of creatine. Consequently, the analysis of standard (1)HMRS examinations in children does not need to take into account interhemispheric differences. PMID- 27364740 TI - OLDER PEOPLE WITH CHRONIC KIDNEY DISEASE: DEFINITION, AND INFLUENCE OF BIOMARKERS AND MEDICATIONS UPON CARDIOVASCULAR AND RENAL OUTCOMES. AB - BACKGROUND: Chronic kidney disease (CKD) is a global problem. With an ageing population the burden on the health services has increased due to the growing number of older people with CKD. This group of individuals is far different to the younger CKD population and their risk of cardiovascular death is far greater than the risk of progressing to end stage kidney disease (ESKD). OBJECTIVE: In this review we explore the role of certain biomarkers and medications in predicting the risk of progression to ESKD and death in old people with CKD. METHODS: An electronic literature search of EMBASE and MEDLINE databases was performed using Healthcare Databases Advanced Search (HDAS) in December 2014. RESULTS: Albuminuria is a key biomarker in predicting the risk of death and progression to ESKD. Cystatin C appears to be superior in predicting the risk of cardiovascular and non-cardiovascular death compared to GFR or creatinine. Several inflammatory biomarkers can be used to predict the risk of death and progression to CKD but measuring and monitoring them in routine clinical practice will be expensive and impractical. The effects of long-term RAAS inhibition in older people are not well established. Older people especially those with CKD receive suboptimal secondary preventive measures. Due to multiple comorbidities older people with CKD are usually receiving a number of medications. This can potentially lead to significant adverse drug events (ADE) due to drug interactions. CONCLUSION: Novel non-traditional risk factors like albuminuria, Cystatin C and inflammatory biomarkers play an important role in predicting their risk of death and progression to ESKD. The efficacy and safety of medications in older people with CKD is not well established and requires more extensive, focused study. PMID- 27364741 TI - Loss of oocytes due to conditional ablation of Murine double minute 2 (Mdm2) gene is p53-dependent and results in female sterility. AB - Murine double minute 2 and 4 (Mdm2, Mdm4) are major p53-negative regulators, preventing thus uncontrolled apoptosis induction in numerous cell types, although their function in the female germ line has received little attention. In the present work, we have generated mice with specific invalidation of Mdm2 and Mdm4 genes in the mouse oocyte (Mdm2(Ocko) and Mdm4(Ocko) mice), to test their implication in survival of these germ cells. Most of the Mdm2(Ocko) but not Mdm4(Ocko) mice were sterile, with a dramatic reduction of the weight of ovaries and genital tract, a strong increase in follicle-stimulating hormone and luteinizing hormone serum levels, and a reduction of anti-mullerian hormone serum levels. Histological analyses revealed an obvious decrease of the number of growing follicles beyond the primary stage in Mdm2(Ocko) ovaries in comparison to controls, with a pronounced increase in the apparition of primary atretic follicles, most being devoid of oocyte. Similar phenotypes were observed with Mdm2(Ocko) Mdm4(Ocko) ovaries, with no worsening of the phenotype. However, we failed to detect any increase in p53 level in mutant oocytes, nor any other apoptotic marker, introgression of this targeted invalidation in p53-/- mice restored the fertility of females. This study is the first to show that Mdm2, but not Mdm4, has a critical role in oocyte survival and would be involved in premature ovarian insufficiency phenotype. PMID- 27364744 TI - Neurodevelopmental disorders: Epilepsy and autism spectrum disorders may have a shared aetiology. PMID- 27364742 TI - Notch1 hallmarks fibrillary depositions in sporadic Alzheimer's disease. AB - BACKGROUND: Notch1 signaling is a cellular cascade with a fundamental role from brain development to adult brain function. Reduction in Notch1 affects synaptic plasticity, memory and olfaction. On the other hand, Notch1 overactivation after brain injury is detrimental for neuronal survival. Some familial Alzheimer's disease (FAD) mutations in Presenilins can affect Notch1 processing/activation. Others report that Notch1 is overexpressed in sporadic Alzheimer's disease (AD). These works indicate that imbalances in Notch1 may be implicated in AD pathophysiology. In this study, we addressed whether Notch1 alteration can be considered a hallmark of AD. RESULTS: Immunohistochemical analysis of Notch1 on cortical and hippocampal tissue from post-mortem patients indicates an accumulation of Notch1 in plaque-like structures in the brain parenchyma of subjects with sporadic AD. Further analysis shows that displaced Notch1 is associated with fibrillary tangles/plaques. Biochemical validation confirms an accumulation of Notch1 in cytosolic brain fractions. This increase in protein is not accompanied with a raise in the Notch1 targets Hes1 and Hey1. Examination of the cerebrospinal fluid (CSF) indicates that the full length and truncations of the Notch1 protein are reduced in AD patients hinting at an accumulation in the brain parenchyma. CONCLUSIONS: Our research indicates that Notch1 is significantly displaced and accumulated in fibrillary structures in the susceptible hippocampal and cortical regions of sporadic AD patients. The dominant deposition of Notch1 in the brain parenchyma and its general signal reduction in neurons is consistent in all the AD patients analyzed and suggests that Notch1 may potentially be considered a novel hallmark of AD. PMID- 27364745 TI - Neuromuscular disease: Methotrexate has no steroid-sparing effect in patients with generalized myasthenia gravis. PMID- 27364746 TI - Parkinson disease: No diagnostic value of alpha-synuclein staining of the colon mucosa in idiopathic Parkinson disease. PMID- 27364747 TI - Alzheimer disease: Elevated neurogranin levels reveal early synaptic damage in APOE* E4 carriers. PMID- 27364743 TI - Vascular endothelial growth factor: a neurovascular target in neurological diseases. AB - Brain function critically relies on blood vessels to supply oxygen and nutrients, to establish a barrier for neurotoxic substances, and to clear waste products. The archetypal vascular endothelial growth factor, VEGF, arose in evolution as a signal affecting neural cells, but was later co-opted by blood vessels to regulate vascular function. Consequently, VEGF represents an attractive target to modulate brain function at the neurovascular interface. On the one hand, VEGF is neuroprotective, through direct effects on neural cells and their progenitors and indirect effects on brain perfusion. In accordance, preclinical studies show beneficial effects of VEGF administration in neurodegenerative diseases, peripheral neuropathies and epilepsy. On the other hand, pathologically elevated VEGF levels enhance vessel permeability and leakage, and disrupt blood-brain barrier integrity, as in demyelinating diseases, for which blockade of VEGF may be beneficial. Here, we summarize current knowledge on the role and therapeutic potential of VEGF in neurological diseases. PMID- 27364748 TI - Sports-related concussions - media, science and policy. AB - Although growing awareness about the potential long-term deleterious effects of sport-related concussion has led to increased attention to the risks of collision sports, calls to ban these sports, such as American football, might be premature. Collision sports have a relatively high incidence of concussions, but participation in these sports also confers a host of benefits. In addition, the associated risks of participation, including concussion, have not been definitively shown to outweigh the benefits they provide, and the risk-benefit ratio might vary among individuals. The risks of concussion and repetitive concussions associated with collision sports are unknown in the general population and not well characterized even in elite athlete populations. In this article, we discuss current knowledge on sports-related concussion, its neurological consequences, and implications for regulation of the practice of collision sports. PMID- 27364749 TI - Cardiac power parameters during hypovolemia, induced by the lower body negative pressure technique, in healthy volunteers. AB - BACKGROUND: Changes in cardiac power parameters incorporate changes in both aortic flow and blood pressure. We hypothesized that dynamic and non-dynamic cardiac power parameters would track hypovolemia better than equivalent flow- and pressure parameters, both during spontaneous breathing and non-invasive positive pressure ventilation (NPPV). METHODS: Fourteen healthy volunteers underwent lower body negative pressure (LBNP) of 0, -20, -40, -60 and -80 mmHg to simulate hypovolemia, both during spontaneous breathing and during NPPV. We recorded aortic flow using suprasternal ultrasound Doppler and blood pressure using Finometer, and calculated dynamic and non-dynamic parameters of cardiac power, flow and blood pressure. These were assessed on their association with LBNP levels. RESULTS: Respiratory variation in peak aortic flow was the dynamic parameter most affected during spontaneous breathing increasing 103 % (p < 0.001) from baseline to LBNP -80 mmHg. Respiratory variation in pulse pressure was the most affected dynamic parameter during NPPV, increasing 119 % (p < 0.001) from baseline to LBNP -80 mmHg. The cardiac power integral was the most affected non dynamic parameter falling 59 % (p < 0.001) from baseline to LBNP -80 mmHg during spontaneous breathing, and 68 % (p < 0.001) during NPPV. CONCLUSIONS: Dynamic cardiac power parameters were not better than dynamic flow- and pressure parameters at tracking hypovolemia, seemingly due to previously unknown variation in peripheral vascular resistance matching respiratory changes in hemodynamics. Of non-dynamic parameters, the power parameters track hypovolemia slightly better than equivalent flow parameters, and far better than equivalent pressure parameters. PMID- 27364750 TI - Pancreatic surgery for tumors in children and adolescents. AB - PURPOSE: Pancreatic neoplasms are uncommon in children. This study sought to analyze the clinical and pathological features of surgically resected pancreatic tumors in children and discuss management strategies. METHODS: We conducted a retrospective review of patients <=21 years with pancreatic neoplasms who underwent surgery at a single institution between 1995 and 2015. RESULTS: Nineteen patients were identified with a median age at operation of 16.6 years (IQR 13.5-18.9). The most common histology was solid pseudopapillary neoplasm (SPN) (n = 13), followed by pancreatic neuroendocrine tumor (n = 3), serous cystadenoma (n = 2) and pancreatoblastoma (n = 1). Operative procedures included formal pancreatectomy (n = 17), enucleation (n = 1) and central pancreatectomy (n = 1). SPNs were noninvasive in all but one case with perineural, vascular and lymph node involvement. Seventeen patients (89.5 %) are currently alive and disease free at a median follow-up of 5.7 (IQR 3.7-10.9) years. Two patients died: one with metastatic insulinoma and another with SPN who developed peritoneal carcinomatosis secondary to a concurrent rectal adenocarcinoma. CONCLUSIONS: Pediatric pancreatic tumors are a heterogeneous group of neoplastic lesions for which surgery can be curative. SPN is the most common histology, is characterized by low malignant potential and in selected cases can be safely and effectively treated with a tissue-sparing resection and minimally invasive approach. PMID- 27364751 TI - From Correlation to Causation: What Do We Need in the Historical Sciences? AB - Changes in the methodology of the historical sciences make them more vulnerable to unjustifiable speculations being passed off as scientific results. The integrity of historical science is in peril due the way speculative and often unexamined causal assumptions are being used to generate data and underpin the identification of correlations in such data. A step toward a solution is to distinguish between plausible and speculative assumptions that facilitate the inference from measured and observed data to causal claims. One way to do that is by comparing these assumptions against a well-attested set of aspects of causation, such as the so-called "Bradford Hill Criteria" (BHC). The BHC do not provide a test for causation or necessary and sufficient conditions for causation but do indicate grounds for further investigation. By revising the BHC to reflect the needs and focus of historical sciences, it will be possible to assess the cogency of methods of investigation. These will be the Historical Sciences Bradford Hill Criteria (HSBHC). An application to one area in historical science is used to demonstrate the effectiveness of the HSBHC, namely biogeography. Four methods are assessed in order to show how the HSBHC can be used to examine the assumptions between our data and the causal biogeographical processes we infer. PMID- 27364752 TI - Targeting Select Cellular Stress Pathways to Prevent Hyperglycemia-Related Complications: Shifting the Paradigm. AB - Despite the advances made in preventing complications of diabetes, there is still substantial residual risk. Hence the need for developing new therapeutic agents that target the various facets of the pathogenesis of complications in people with diabetes. Traditionally four general biochemical pathways had been recognized as major contributors to glucotoxicity. These include the polyol pathway, the protein kinase C (PKC) pathway, glycosylation pathway, and oxidative stress. The latter has been proposed as a common impetus of the other pathways of glucotoxicity. More recently, the cross talk between oxidative stress and other recognized cellular stresses such as endoplasmic reticulum (ER), inflammatory, and mitochondrial stresses has emerged as an important additional mechanism of glucotoxicity. The observation that targeting oxidative stress with antioxidants has been associated with unfavorable clinical outcomes and the recognition that in cell cultures antioxidants may aggravate ER stress, suggests that selective targeting of individual cellular stresses may not be sufficient for preventing glucotoxicity. Future efforts should focus on developing therapeutic agents that can ameliorate cellular stress globally by simultaneously targeting the oxidative, ER, mitochondrial, and inflammatory stresses. PMID- 27364754 TI - Learning to live with Parkinson's disease in the family unit: an interpretative phenomenological analysis of well-being. AB - We investigated family members' lived experience of Parkinson's disease (PD) aiming to investigate opportunities for well-being. A lifeworld-led approach to healthcare was adopted. Interpretative phenomenological analysis was used to explore in-depth interviews with people living with PD and their partners. The analysis generated four themes: It's more than just an illness revealed the existential challenge of diagnosis; Like a bird with a broken wing emphasizing the need to adapt to increasing immobility through embodied agency; Being together with PD exploring the kinship within couples and belonging experienced through support groups; and Carpe diem! illuminated the significance of time and fractured future orientation created by diagnosis. Findings were interpreted using an existential-phenomenological theory of well-being. We highlighted how partners shared the impact of PD in their own ontological challenges. Further research with different types of families and in different situations is required to identify services required to facilitate the process of learning to live with PD. Care and support for the family unit needs to provide emotional support to manage threats to identity and agency alongside problem-solving for bodily changes. Adopting a lifeworld-led healthcare approach would increase opportunities for well-being within the PD illness journey. PMID- 27364753 TI - Management of Myopic Choroidal Neovascularization: Focus on Anti-VEGF Therapy. AB - Myopic choroidal neovascularization (mCNV) is the second most common form of CNV after age-related macular degeneration (AMD). It is a sight-threatening complication of pathologic myopia (PM) and often affects patients in their working years causing significant impact on quality of life. Previous therapies such as photodynamic therapy with verteporfin have shown limited success. Due to the similarities in pathogenesis of mCNV and AMD CNV, anti-vascular endothelial growth factor therapy (anti-VEGF), which has so far been the mainstay of treatment for AMD CNV, has been shown to be effective in the treatment of mCNV and has become the first-line treatment of choice. This article aims to examine briefly the epidemiology and pathophysiology of mCNV, as well as review the evidence for efficacy, safety, and clinical use of anti-VEGF treatment for mCNV. PMID- 27364755 TI - Factors Associated With Ineligibility for PCI Differ Between Inpatient and Outpatient ST-Elevation Myocardial Infarction. AB - OBJECTIVES: Without early revascularization, both inpatient and outpatient STEMIs have poor outcomes. Reasons for denying PCI for STEMI, however, remain uncertain. This single-center retrospective cohort study compares factors and outcomes associated with ineligibility for PCI between inpatients and outpatients following ST-elevation myocardial infarction (STEMI). METHODS: A total of 1,759 STEMI patients between June 2009 and January 2015 were assessed. Individual medical records were reviewed to obtain reasons for PCI ineligibility for STEMI patients who did not receive reperfusion therapy. RESULTS: Compared to outpatients with STEMI (n = 1,688), inpatients (n = 71) were less likely to receive coronary angiography (60.6% vs 95.9%; P < 0.001) or PCI (50.7% vs 80.9%; P < 0.001), with longer ECG/door to first device activation times (97 [78, 131] vs 63 [49, 78] minutes; P < 0.001). When coronary angiography was performed, however, similar rates of PCI and procedural success were seen in both groups. Principal contraindication for PCI was risk of bleeding within the inpatient population and complex coronary artery disease within the outpatient population. Total in-hospital mortality was higher in inpatient STEMIs compared to outpatients (42.2% vs 10.0%; P < 0.001), but lower for patients eligible for PCI in both groups. CONCLUSIONS: Reasons for PCI ineligibility differ between inpatient and outpatient STEMIs. Inpatients have increased risks of bleeding, lower coronary angiography and PCI use, and higher in-hospital mortality. Especially for inpatients, specific PCI STEMI protocols that anticipate and overcome types of ineligibility and delay for cardiac catheterization may improve outcomes. PMID- 27364757 TI - Toll-like receptors in the pathogenesis of pulmonary fibrosis. AB - Pulmonary fibrosis (PF) constitutes the end stage of a broad range of heterogeneous interstitial lung diseases, characterized by the destruction of the pulmonary parenchyma, deposition of extracellular matrix and dramatic changes in the phenotype of both fibroblasts and alveolar epithelial cells. More than 200 causes of pulmonary fibrosis have been identified so far, yet the most common form is idiopathic pulmonary fibrosis (IPF). IPF is a lethal lung disorder of unknown etiology with a gradually increasing worldwide incidence and a median survival of 3-5 years from the time of diagnosis. Despite intense research efforts, the pathogenesis remains elusive and no effective treatment is available. Accumulating body of evidence suggests an abnormal wound healing response followed by extracellular matrix deposition, destruction of lung architecture, ultimately leading to respiratory failure. The contribution of immune system in lung fibrogenesis had been largely underscored due to the absence of response to immunosuppressive agents; however, the premise that lung fibrosis has an immunologic background has been recently revived. Toll-like receptors (TLRs) are pattern recognition receptors (PRRs), which link innate and adaptive immune response and regulate wound healing. TLRs promote tissue repair or fibrosis in many disease settings including lung fibrosis, albeit with profound differences depending on the cellular microenvironment. This review summarizes the current state of knowledge regarding the mechanistic implications between TLRs and lung fibrosis and highlights the therapeutic potential of targeting TLR signaling at the ligand or receptor level. PMID- 27364756 TI - Interleukin-1beta has trophic effects in microglia and its release is mediated by P2X7R pore. AB - BACKGROUND: Enhanced expression of the purinergic P2X7 receptor (P2X7R) occurs in several neuroinflammatory conditions where increased microglial activation is a co-existing feature. P2X7 receptors can function either as a cation channel or, upon continued stimulation, a large pore. P2X7R-over-expression alone is sufficient to drive microglial activation and proliferation in a process that is P2X7R pore dependent, although the biological signaling pathway through which this occurs remains unclear. Once activated, microglia are known to release a number of bioactive substances that include the proinflammatory cytokine interleukin-1beta (IL-1beta). Previous studies have linked P2X7R stimulation to the processing and release of IL-1beta, but whether the channel or pore state of P2X7R is predominant in driving IL-1beta release is unknown and is a major aim of this study. In addition, we will determine whether IL-1beta has trophic effects on surrounding microglia. METHODS: Electron microscopy and immunohistochemistry were used to delineate the sub-cellular localization of P2X7R and IL-1beta in primary hippocampal rat cultures. FM1-43 fluorescent dye and confocal microscopy were used to quantify vesicular exocytosis from microglia expressing the pore forming P2X7R versus a non-pore-forming point mutant, P2X7RG345Y. IL-1beta in culture was quantified with an enzyme-linked immunosorbent assay (ELISA). IL 1beta intracellular processing was blocked with inhibition of caspase 1 (with a synthetic peptide antagonist), and its extracellular form was neutralized with an IL-1beta neutralizing antibody. Microglial activation and proliferation was quantified immunohistochemically with confocal microscopy. RESULTS: P2X7R and IL 1beta were co-localized in lysosomes. Vesicular exocytosis was higher in microglia expressing the pore-forming P2X7R compared to those expressing the non pore-forming mutant. There was increased IL-1beta in cultures expressing the pore forming P2X7R, and this proinflammatory cytokine was found to mediate the trophic effects of P2X7R pore in microglia. Inhibition of IL-1beta production and function resulted in a significant decrease in P2X7R-mediated microglial activation and proliferation. CONCLUSIONS: IL-1beta is a mediator of microglial activation and proliferation, and its release/production is P2X7R pore dependent. Blockade of P2X7R pore could serve as a therapeutic target in alleviating the degree of inflammation seen in neurodegenerative and neoplastic conditions. PMID- 27364758 TI - Interactions between calcium channels and SK channels in midbrain dopamine neurons and their impact on pacemaker regularity: Contrasting roles of N- and L type channels. AB - Although small-conductance Ca(2+)-activated K(+) (SK) channels and various types of voltage-gated Ca(2+) (Cav) channels have been described in midbrain dopaminergic neurons, the nature of their interactions is unclear. More particularly, the role of various Cav channel types in either promoting irregularity of firing (by generating an inward current during SK channel blockade) or promoting regularity of firing (by providing the source of Ca(2+) for the activation of SK channels) has not been systematically explored. We addressed this question using intracellular and extracellular recordings from substantia nigra, pars compacta (SNc), dopaminergic neurons in rat midbrain slices. Neurons were pharmacologically isolated from their differences. When examining the ability of various Cav channel blockers to inhibit the SK-mediated afterhyperpolarization (AHP), we found that only the N-type Cav channel blocker omega-conotoxin-GVIA was able to reduce the apamin-sensitive AHP, but only partially (~40%). Specific blockers of L, P/Q, T or R channels had no effect on this AHP. Combining omega-conotoxin-GVIA and other specific blockers did not yield greater block and even the broad Cav blocker Cd(2+) induced a submaximal (~75%) effect. Extracellular recordings examining firing regularity yielded congruent results: none of the specific blockers was able to increase firing irregularity to the extent that the specific SK blocker apamin did. The irregularity of firing observed with apamin could only be reversed by blocking L type Ca(2+) channels. Thus various sources of Ca(2+) appear to be required for SK channel activation in SNc neurons (some of them still unidentified), ensuring robustness of pacemaking regularity. PMID- 27364759 TI - Two-Dimensional-Material Membranes: A New Family of High-Performance Separation Membranes. AB - Two-dimensional (2D) materials of atomic thickness have emerged as nano-building blocks to develop high-performance separation membranes that feature unique nanopores and/or nanochannels. These 2D-material membranes exhibit extraordinary permeation properties, opening a new avenue to ultra-fast and highly selective membranes for water and gas separation. Summarized in this Minireview are the latest ground-breaking studies in 2D-material membranes as nanosheet and laminar membranes, with a focus on starting materials, nanostructures, and transport properties. Challenges and future directions of 2D-material membranes for wide implementation are discussed briefly. PMID- 27364760 TI - Prediction of self-care behaviour on the basis of knowledge about chronic kidney disease using self-efficacy as a mediator. AB - AIMS AND OBJECTIVES: This study was to investigate: (1) the important factors in the self-care of chronic kidney disease (CKD) patients and (2) the mediating effects of self-efficacy on knowledge and self-care. BACKGROUND: Chronic kidney disease has become a major global health issue and is one of the top 10 leading causes of death in Taiwan where the dialysis population ranks first in the world. The number of patients with poor self-care behaviours continues to rise despite ongoing health education. Knowledge and self-efficacy are important factors that influence self-care behaviour; however, very few articles have examined the relationships among them. DESIGN: Cross-sectional and correlational design. METHODS: Subject recruitment was conducted by purposive sampling in the renal outpatient clinics and dialysis centres of two teaching hospitals in northern Taiwan. A total of 247 patients with chronic kidney disease (stages 1-5) were enrolled. RESULTS: (1) Knowledge was positively correlated with self-efficacy (r = 0.41, p < 0.01) and with self-care (r = 0.18, p < 0.01). Self-efficacy (r = 0.44, p < 0.01) as well as age (r = 0.15, p < 0.01) were positively correlated with self-care. (2) The relationship between knowledge and self-care was fully mediated by self-efficacy (z = 4.82, p < 0.001) and the effect was 50%. CONCLUSION: The results showed that self-efficacy was a crucial mediator between knowledge and self-care. In addition to providing knowledge to chronic kidney disease patients, healthcare professionals should also offer strategies that can enhance self-efficacy to increase self-care behaviours in chronic kidney disease patients and implement effective disease management. RELEVANCE TO CLINICAL PRACTICE: Incorporate self-efficacy strategies into the process of health education to improve knowledge and the effectiveness of self-care. The findings of this study provide evidence of effectiveness of the use of group activity through self-management and self-efficacy enhancement programmes and may influence the policy makers to consider adding or modifying the reimbursement criteria. PMID- 27364761 TI - Physician health programs under fire. PMID- 27364762 TI - Review: welfare of dairy cows in continuously housed and pasture-based production systems. AB - There is increasing interest in the use of continuous housing systems for dairy cows, with various reasons put forward to advocate such systems. However, the welfare of dairy cows is typically perceived to be better within pasture-based systems, although such judgements are often not scientifically based. The aim of this review was to interrogate the existing scientific literature to compare the welfare, including health, of dairy cows in continuously housed and pasture-based systems. Although summarising existing work, knowledge gaps and directions for future research are also identified. The scope of the review is broad, examining relevant topics under three main headings; health, behaviour and physiology. Regarding health, cows on pasture-based systems had lower levels of lameness, hoof pathologies, hock lesions, mastitis, uterine disease and mortality compared with cows on continuously housed systems. Pasture access also had benefits for dairy cow behaviour, in terms of grazing, improved lying/resting times and lower levels of aggression. Moreover, when given the choice between pasture and indoor housing, cows showed an overall preference for pasture, particularly at night. However, the review highlighted the need for a deeper understanding of cow preference and behaviour. Potential areas for concern within pasture-based systems included physiological indicators of more severe negative energy balance, and in some situations, the potential for compromised welfare with exposure to unpredictable weather conditions. In summary, the results from this review highlight that there remain considerable animal welfare benefits from incorporating pasture access into dairy production systems. PMID- 27364764 TI - [The approach to active and passive smoking in the Paediatric Clinic]. PMID- 27364763 TI - Antacid attenuates the laxative action of magnesia in cancer patients receiving opioid analgesic. AB - OBJECTIVE: This study was designed to investigate pharmacological interaction between magnesium laxative and antacid in patients receiving opioid analgesic. METHODS: Data obtained from a total of 441 eligible patients receiving opioid analgesic for the first time were retrospectively analysed. The incidence of constipation, defined as stool-free interval of 3 days and more within the first week of opioid intake, was compared between patients who took laxative alone and those who received laxative in combination with antacid. KEY FINDINGS: Laxatives were prescribed in 74% of patients, among them 61% received antacids such as proton pump inhibitor and H2 receptor blocker. Magnesia was the most commonly used laxative (89%). Constipation occurred in 21% and 55% of patients with and without laxatives, respectively. Antacids reversed the laxative action of lower doses (<2000 mg/day) but not higher doses (>2000 mg/day) of magnesia without affecting the effects of other laxatives. Therefore, it is suggested that both acid-dependent and acid-independent mechanisms may operate in the laxative action of magnesia, in which the former may be involved in the action of lower doses of magnesia. CONCLUSION: Care should be taken to avoid the unfavourable pharmacological interaction between low doses of magnesia and antacid. PMID- 27364766 TI - Complement resistance mechanisms of Klebsiella pneumoniae. AB - The current emergence of antibiotic-resistant bacteria causes major problems in hospitals worldwide. To survive within the host, bacterial pathogens exploit several escape mechanisms to prevent detection and killing by the immune system. As a major player in immune defense, the complement system recognizes and destroys bacteria via different effector mechanisms. The complement system can label bacteria for phagocytosis or directly kill Gram-negative bacteria via insertion of a pore-forming complex in the bacterial membrane. The multi-drug resistant pathogen Klebsiella pneumoniae exploits several mechanisms to resist complement. In this review, we present an overview of strategies used by K. pneumoniae to prevent recognition and killing by the complement system. Understanding these complement evasion strategies is crucial for the development of innovative strategies to combat K. pneumoniae. PMID- 27364765 TI - A novel AhR ligand, 2AI, protects the retina from environmental stress. AB - Various retinal degenerative diseases including dry and neovascular age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy are associated with the degeneration of the retinal pigmented epithelial (RPE) layer of the retina. This consequently results in the death of rod and cone photoreceptors that they support, structurally and functionally leading to legal or complete blindness. Therefore, developing therapeutic strategies to preserve cellular homeostasis in the RPE would be a favorable asset in the clinic. The aryl hydrocarbon receptor (AhR) is a conserved, environmental ligand-dependent, per ARNT-sim (PAS) domain containing bHLH transcription factor that mediates adaptive response to stress via its downstream transcriptional targets. Using in silico, in vitro and in vivo assays, we identified 2,2'-aminophenyl indole (2AI) as a potent synthetic ligand of AhR that protects RPE cells in vitro from lipid peroxidation cytotoxicity mediated by 4-hydroxynonenal (4HNE) as well as the retina in vivo from light-damage. Additionally, metabolic characterization of this molecule by LC-MS suggests that 2AI alters the lipid metabolism of RPE cells, enhancing the intracellular levels of palmitoleic acid. Finally, we show that, as a downstream effector of 2AI-mediated AhR activation, palmitoleic acid protects RPE cells from 4HNE-mediated stress, and light mediated retinal degeneration in mice. PMID- 27364768 TI - SnO2 as a high-efficiency polysulfide trap in lithium-sulfur batteries. AB - The ithium-sulfur battery stands as one of the most promising successors of traditional lithium-ion batteries due to its super high theoretical energy density, but practical application still suffers from the shuttle effect arising from soluble intermediate polysulfides. Here, we report SnO2 as a chemical adsorbent for polysulfides. As an interlayer between the cathode and separator, SnO2 gives better results to prevent the polysulfides from diffusing to the lithium anode than as a modifier of the carbon matrix directly. The lithium sulfur battery with an SnO2 interlayer delivers an initial reversible capacity of 996 mA h g(-1) and retains 832 mA h g(-1) at the 100(th) discharge at 0.5 C, with a fading rate of only 0.19% per cycle. The improvements benefit from the quasi open space provided by the interlayer configuration for the diffused sulfur species, which can largely relieve the loss of active substances caused by the volume effect during the lithiation/delithiation process. PMID- 27364767 TI - First Person Perspective of Seated Participants Over a Walking Virtual Body Leads to Illusory Agency Over the Walking. AB - Agency, the attribution of authorship to an action of our body, requires the intention to carry out the action, and subsequently a match between its predicted and actual sensory consequences. However, illusory agency can be generated through priming of the action together with perception of bodily action, even when there has been no actual corresponding action. Here we show that participants can have the illusion of agency over the walking of a virtual body even though in reality they are seated and only allowed head movements. The experiment (n = 28) had two factors: Perspective (1PP or 3PP) and Head Sway (Sway or NoSway). Participants in 1PP saw a life-sized virtual body spatially coincident with their own from a first person perspective, or the virtual body from third person perspective (3PP). In the Sway condition the viewpoint included a walking animation, but not in NoSway. The results show strong illusions of body ownership, agency and walking, in the 1PP compared to the 3PP condition, and an enhanced level of arousal while the walking was up a virtual hill. Sway reduced the level of agency. We conclude with a discussion of the results in the light of current theories of agency. PMID- 27364769 TI - Molecular design of light-harvesting photosensitizers: effect of varied linker conjugation on interfacial electron transfer. AB - Interfacial electron transfer dynamics of a series of photosensitizers bound to TiO2via linkers of varying conjugation strength are explored by spectroscopic and computational techniques. Injection and recombination depend on the extent of conjugation in the linker, where the LUMO delocalization determines the injection dynamics but both the HOMO and HOMO-1 are involved in recombination. PMID- 27364771 TI - Plasma Pharmacokinetics of Veledimex, a Small-Molecule Activator Ligand for a Proprietary Gene Therapy Promoter System, in Healthy Subjects. AB - Major obstacles to developing effective immunotherapy are the ability of tumors to escape the immune system and the toxicity associated with systemic administration. To overcome these challenges, a gene delivery platform technology, RheoSwitch Therapeutic System (RTS), has been developed to enable the regulated expression of a target gene, Ad-RTS-IL-12, administered intratumorally, where IL-12 expression is controlled via the administration of an oral activator ligand, veledimex. Pharmacokinetics in healthy human subjects indicated that veledimex plasma exposure increased with increasing dose after single- and multiple-dose administration in Labrasol slurry and F-22 capsule formulations. No apparent formulation or sex-related difference in veledimex pharmacokinetics (PK) was observed. Minimal or no plasma accumulation of veledimex was observed after once-daily oral administration for 14 days. Veledimex steady state in plasma was reached after 5 daily doses. Food consumption prior to veledimex administration prolonged and enhanced absorption with no impact on the elimination rate and extent of metabolism of veledimex, resulting in significantly increased systemic exposure to veledimex and its 2 major circulating metabolites. Overall, veledimex was well tolerated and exhibited a PK profile supportive of once-daily dosing. For enhanced efficacy, veledimex should be taken under fed conditions to ensure optimal absorption and sufficient systemic exposure. PMID- 27364772 TI - New insights into the clinical neurophysiological assessment of ALS. PMID- 27364770 TI - MNK Inhibition Disrupts Mesenchymal Glioma Stem Cells and Prolongs Survival in a Mouse Model of Glioblastoma. AB - : Glioblastoma multiforme remains the deadliest malignant brain tumor, with glioma stem cells (GSC) contributing to treatment resistance and tumor recurrence. We have identified MAPK-interacting kinases (MNK) as potential targets for the GSC population in glioblastoma multiforme. Isoform-level subtyping using The Cancer Genome Atlas revealed that both MNK genes (MKNK1 and MKNK2) are upregulated in mesenchymal glioblastoma multiforme as compared with other subtypes. Expression of MKNK1 is associated with increased glioma grade and correlated with the mesenchymal GSC marker, CD44, and coexpression of MKNK1 and CD44 predicts poor survival in glioblastoma multiforme. In established and patient-derived cell lines, pharmacologic MNK inhibition using LY2801653 (merestinib) inhibited phosphorylation of the eukaryotic translation initiation factor 4E, a crucial effector for MNK-induced mRNA translation in cancer cells and a marker of transformation. Importantly, merestinib inhibited growth of GSCs grown as neurospheres as determined by extreme limiting dilution analysis. When the effects of merestinib were assessed in vivo using an intracranial xenograft mouse model, improved overall survival was observed in merestinib-treated mice. Taken together, these data provide strong preclinical evidence that pharmacologic MNK inhibition targets mesenchymal glioblastoma multiforme and its GSC population. IMPLICATIONS: These findings raise the possibility of MNK inhibition as a viable therapeutic approach to target the mesenchymal subtype of glioblastoma multiforme. Mol Cancer Res; 14(10); 984-93. (c)2016 AACR. PMID- 27364773 TI - Outcome of two-muscle surgery for large-angle intermittent exotropia in children. AB - BACKGROUND/AIMS: To evaluate the surgical outcomes of two-muscle surgery for childhood intermittent exotropia comparing large angles with moderate angles. METHODS: We retrospectively reviewed the medical records of 178 children who had undergone bilateral lateral rectus recession (BLR) or unilateral recess-resect (RR) for large-angle (>=40 prism dioptres (PD); group A) or moderate-angle (>=20 and <30 PD; group B) intermittent exotropia with a postoperative follow-up period of 6 months or more. The main outcome measures were postoperative deviation angle and surgical success rate, and the secondary outcome measure was effect/dose ratio. The effect/dose ratio was defined as the corrected angle of deviation at postoperative 6 months divided by the sum of the amount of lateral rectus recession in each eye in BLR and by the sum of the amount of lateral rectus recession and medial rectus resection in RR. Surgical success was defined as alignment between 10 PD of exodeviation and 5 PD of esodeviation both at distance and at near. RESULTS: There was a significant difference in mean angle of deviation at distance throughout the postoperative period (p<0.05). The final surgical success rate was significantly lower in group A than in group B (p<0.05). The effect/dose ratio for both BLR and unilateral RR was significantly greater in group A than in group B (p<0.05). CONCLUSIONS: The patients with childhood intermittent exotropia with large angles showed significantly higher rates of undercorrection, though they also showed greater effects of BLR or RR per millimetre (the effect/dose ratio), compared with moderate-angle exotropia. PMID- 27364774 TI - Association between personal basic information, sleep quality, mental disorders and erectile function: a cross-sectional study among 334 Chinese outpatients. AB - Male erectile dysfunction (ED) may cause anxiety and depression, while mental disorders and sleep disturbances may also be closely related to ED. However, the exact nature of their relationship remains unclear, and whether personal basic background data affect erectile function is unknown. We conducted a cross sectional study among Chinese outpatients with ED from January 2012 to December 2014. All the men answered a questionnaire collecting information about mental health status, sleep disturbances and personal data, underwent a physical examination and had a blood sample drawn. Sleep disturbances were assessed on the basis of a 19-item version of the Pittsburgh Sleep Quality Index, which includes questions on sleep patterns during the past month. Among the 462 patients, 128 patients with alcohol abuse, diabetes, hypertension, hyperlipidaemia, psychiatric drugs, neurologic injury or abnormal hormones were excluded from the study; 86.27% and 68.66% of the patients suffered from anxiety and depression respectively. Sleep quality and anxiety symptoms significantly affected erectile function, whereas personal income and education level had no significant effects. Our study suggested that it is necessary to pay attention to the psychological status of patients with ED, especially anxiety disorder. Sleep quality may be an important factor affecting erectile function according to the personal data. PMID- 27364775 TI - A comprehensive capacity assessment tool for non-communicable diseases in low- to middle-income countries: development and results of pilot testing. AB - Non-communicable diseases (NCDs) are the leading causes of death worldwide, with higher rates of premature mortality in low- and middle-income countries (LMICs). This places a high economic burden on these countries, which usually have limited capacity to address this public health problem. We developed a guided self assessment tool for describing national capacity for NCD prevention and control. The purpose of this tool was to assist countries in identifying key opportunities and gaps in NCD capacity. It was piloted in three countries between 2012 and 2013: Mozambique, Colombia, and the Dominican Republic. The tool includes details about NCD burden; health system infrastructure and primary care services; workforce capacity; surveillance; planning, policy, and program management; and partnerships. In the three pilot countries, the tool helped to identify differences in capacity needs pertaining to staff, training, and surveillance, but similarities were also found related to NCD challenges and opportunities. The NCD tool increased our understanding of needs and critical capacity elements for addressing NCDs in the three pilot countries. This tool can be used by other LMICs to map their efforts toward addressing NCD goals and defining priorities. PMID- 27364776 TI - Individual, social-environmental, and physical-environmental factors that underlie sense of coherence in Dutch adults. AB - Antonovsky's salutogenesis is a theoretical perspective on health development that explores physical, mental, and social factors that contribute to a 'healthy life orientation' and also a theoretical approach to behavior change. Previous studies applying salutogenesis show that a high sense of coherence (SOC), a composite measure from salutogenesis indicating one's capacity to cope with stress, is associated with a healthy life orientation and lifestyle behaviors, including healthy eating patterns. However, limited evidence exists on the factors that underlie SOC, which could be used to strengthen this capacity as a means to enable healthier eating. Dutch adults ( N = 781) participated in a cross sectional study examining the relationship between SOC and a set of individual, social-environmental, and physical-environmental factors. The main findings indicate that high SOC was associated with a diverse set of factors including lower doctor-oriented health locus of control; higher satisfaction with weight; higher perceived levels of neighborhood collective efficacy; higher situational self-efficacy for healthy eating; lower social discouragement for healthy eating; and higher neighborhood affordability, accessibility and availability of healthy foods. These findings can inform the design of nutrition interventions that target these factors that strengthen SOC and provide the building blocks for a healthier life orientation. PMID- 27364777 TI - Acquired Mutism and Hypertonia in a Toddler. PMID- 27364778 TI - On Pins and Needles: Complex Pain and Malnutrition. PMID- 27364779 TI - Setting-based interventions to promote mental health at the university: a systematic review. AB - OBJECTIVES: Universities are dynamic environments. But university life presents challenges that may affect the mental health of its community. Higher education institutions provide opportunities to promote public health. Our objective is to summarise the current evidence on strategies to promote mental health at the university, following a setting-based model. METHODS: We conducted a systematic literature review following standard methods. Published literature that evaluated structural and organizations strategies to promote mental health at the university was selected. RESULTS: 19 papers were included. The majority of the studies were targeting the students, with only four aiming to promote employees' mental health. The most promising strategies to promote mental wellbeing included changes in the way students are taught and assessed. On the other hand, social marketing strategies had not impact on mental health. There is inconclusive evidence related to the effectiveness of policies to promote mental health. CONCLUSIONS: Universities should invest in creating supportive physical, social and academic environments that promote student and staff mental wellbeing. However, the current body of evidence is scarce and more research is needed to recommend what are the best strategies. PMID- 27364781 TI - Comparison of PI-RADS 2, ADC histogram-derived parameters, and their combination for the diagnosis of peripheral zone prostate cancer. AB - PURPOSE: The purpose of this study was to compare the PI-RADS V2 scores, ADC histogram-derived parameters, and their combination for the diagnosis of clinically significant peripheral zone prostate cancer (PCa). MATERIALS AND METHODS: The IRB approved this retrospective study of 47 men who underwent 1.5 Tesla endorectal prostate magnetic resonance imaging (MRI). Informed consent was waived. Two readers identified and scored MRI lesions using PI-RADS V2. Their mean, median, 10th, 25th, 75th percentile ADC values, and normalized ratio were also calculated. Multilevel logistic regression and receiver-operating characteristic (ROC) curve analyses assessed their diagnostic performance. Clinically significant PCa was defined as tumor volume over 0.5 cc and Gleason grade of 4 or 5 on prostatectomy. RESULTS: The area under the ROC curve (A z) of the overall and diffusion-weighted imaging (DWI) PI-RADS V2 scores were 0.69 and 0.84 (reader-1), and 0.68 and 0.73 (reader-2). The A z of ADC parameters ranged from 0.68 to 0.75 for both readers. Compared to other predictors, DWI PI-RADS V2 yielded the highest A z for identification of significant cancer; but, except for reader-1 75th percentile ADC, the differences were not statistically significant (P > 0.05). Adding ADC parameters to PI-RADS V2 scores did not improve their diagnostic ability. CONCLUSION: DWI PI-RADS V2 score may a better predictor of clinically significant PCa than the overall PI-RADS V2 score, but its diagnostic performance was not significantly improved by the addition of objective ADC value measurements. PMID- 27364780 TI - Decreased CX3CR1 messenger RNA expression is an independent molecular biomarker of early and late mortality in critically ill patients. AB - BACKGROUND: Chemokine (C-X3-C motif) receptor 1 (CX3CR1) was identified as the most differentially expressed gene between survivors and non-survivors in two independent cohorts of septic shock patients and was proposed as a marker of sepsis-induced immunosuppression. Whether such a biomarker is associated with mortality in the heterogeneous group of critically ill patients is unknown. The primary objective of this study was to evaluate the association between CX3CR1 messenger RNA (mRNA) expression and mortality in intensive care unit (ICU) patients. The secondary objective was to evaluate similar endpoints in the subgroup of septic shock patients. METHODS: We performed a prospective, multicentre, non-interventional study in six ICUs of university hospitals in Lyon, France. Every consecutive adult patient with systemic inflammatory response syndrome and an expected length of stay in the ICU over 2 days was included. Whole-blood CX3CR1 mRNA expression was measured by quantitative real-time polymerase chain reaction at day 1 (D1) and D3 after inclusion. RESULTS: In ICU patients (n = 725), decreased CX3CR1 mRNA expression at D1 was associated with high D7 mortality (AUC 0.70, adjusted OR [aOR] 2.03, 95 % CI 1.19-3.46), while decreased expression at D3 was associated with increased D28 mortality (AUC 0.64, aOR 2.34, 95 % CI 1.45-3.77). In septic shock patients (n = 279), similar associations were observed between decreased D1 CX3CR1 mRNA expression and D7 mortality (AUC 0.69, aOR 2.76, 95 % CI 1.32-5.75) as well as decreased D3 expression and D28 mortality (AUC 0.72, aOR 3.98, 95 % CI 1.72-9.23). These associations were independent of lactacidaemia, Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment score and Charlson comorbidity index. CONCLUSIONS: This study represents the largest evaluation of such an mRNA marker in a heterogeneous cohort of severely injured patients. Our results show that decreased CX3CR1 mRNA expression is associated with increased mortality in ICU patients. This suggests a link between injury-induced immunosuppression and mortality in critically ill patients. In this context, the monitoring of such a host response molecular biomarker could prove very helpful for the identification of patients at high risk of death in the ICU. PMID- 27364782 TI - Case of acute lead toxicity associated with Ayurvedic supplements. AB - Use of traditional folkloric remedies not disclosed to the physician may be difficult to identify as a source of lead toxicity. This report illustrates the presentation of a 26-year-old man who, during his 1 month vacation in India, was treated for low back pain with Ayurvedic herbal medicine. On his return to the USA, he presented to the emergency department with epigastric pain, weight loss, dark stools, nausea and vomiting. He was admitted and noted to be anaemic with a blood lead level (BLL) of 94.8 ug/dL. Peripheral blood smear demonstrated basophilic stippling. Chelation therapy with succimer was initiated. The patient became asymptomatic within months. Three years later, he remained asymptomatic with BLL <20 ug/dL. Physicians should be cognisant of potential toxicity from these Ayurvedic medications and have a heightened level of suspicion for lead toxicity in the face of anaemia and abdominal pain without obvious cause. PMID- 27364783 TI - Red blood cell antigen alloimmunization: Mysteries still unsolved. PMID- 27364784 TI - Infectivity of Immature Neurons to Zika Virus: A Link to Congenital Zika Syndrome. AB - BACKGROUND: Epidemiological data strongly suggest that microcephaly cases in Brazil are associated with the ongoing epidemic of Zika virus (ZIKV). In order to further solidify the possible link, we investigated the infectivity of ZIKV using various neuroblastoma (NB) cell lines. METHODS: Six undifferentiated, two terminally differentiated and two retinoic acid (RA) -induced, partially differentiated cell lines were exposed to ZIKV strain PRVABC59, which is genetically similar to the French Polynesia strain, with 97-100% genetic homology to the current ZIKV strain found in Brazil. All infections were confirmed by real time PCR (RT-qPCR), immunofluorescence assay (IFA) probing with anti-flavivirus E antibody, and evaluation of cytopathic effects. FINDINGS: ZIKV infected all six undifferentiated NB cell lines. In five out of six NB cell lines, between 90 and 70% cells were positive by IFA whereas for one cell line, CCL-127, ~80% of cells were positive for ZIKV as determined by IFA but showed persistent infection. Two differentiated cell lines, JFEN and T-268, were highly resistant to ZIKV with <1% of the cells being susceptible, as determined by IFA and confirmed by qRT-PCR. Two retinoic acid (RA)-induced NB partially differentiated cell lines showed no difference in permissiveness as compared to their undifferentiated mother cell lines. INTERPRETATION: These findings strengthen the reported association between high incidences of microcephaly and ZIKV infection in newborns in Brazil. Our results suggest that the undifferentiated neurons are highly permissive to ZIKV infection, as one would expect during the early stages of neurogenesis in fetal brains; whereas differentiated neurons, representative of adult brain neurons, are relatively resistant to the virus, which explains the rare occurrence of neurological complications in adults infected with ZIKV. Our studies confirm the neurotropism of the ZIKV strain closely related to the current epidemic in Latin America. PMID- 27364785 TI - Association of Different Human Rhinovirus Species with Asthma in Children: A Preliminary Study. AB - BACKGROUND: Human rhinoviruses (HRVs) are divided into three genetic species: HRV A, HRV-B, and HRV-C. The association of different HRV species with asthma in children in China has not yet been evaluated. This preliminary study aimed to assess the associations between different HRV species, particularly HRV-C, and asthma in young children in China. METHODS: A total of 702 nasopharyngeal aspirates were obtained from 155 children with asthma (asthma group), 461 children with acute respiratory infection (ARI) without asthma (nonasthma ARI group), and 86 children from the control group. Semi-nested polymerase chain reaction (PCR) was used to detect HRVs, and PCR products were sequenced for species identification. Epidemiological characteristics of HRV-positive cases were analyzed. RESULTS: HRVs were the most common pathogen (15.4%; 108/702) in the patients in this study. The prevalence of HRV was significantly different (F = 20.633, P = 0.000) between the asthma (25.8%) and nonasthma ARI groups (11.1%). Phylogenetic analysis indicated that in the 108 cases positive for HRVs, 41 were identified as HRV-A, 8 as HRV-B, and 56 as HRV-C. Comparing the asthma with the nonasthma ARI group, Spearman's rank correlation analysis revealed an association between HRV-A (P < 0.05) and C (P < 0.01) and asthma, confirmed by regression analysis, with odds ratios of 2.2 (HRV-A) and 4.2 (HRV-C). CONCLUSIONS: Our data revealed a high prevalence of HRVs in children in China, regardless of clinical status. HRV-C was the dominant species and may be one of the key factors in the association of HRVs with asthma. PMID- 27364786 TI - Tumor Necrosis Factor-alpha Induced Protein 3 Interacting Protein 1 Gene Polymorphisms and Pustular Psoriasis in Chinese Han Population. AB - BACKGROUND: Psoriasis is a common immune-mediated inflammatory dermatosis. Generalized pustular psoriasis (GPP) is the severe and rare type of psoriasis. The association between tumor necrosis factor-alpha induced protein 3 interacting protein 1 (TNIP1) gene and psoriasis was confirmed in people with multiple ethnicities. This study was to investigate the association between TNIP1 gene polymorphisms and pustular psoriasis in Chinese Han population. METHODS: Seventy three patients with GPP, 67 patients with palmoplantar pustulosis (PPP), and 476 healthy controls were collected from Chinese Han population. Six single nucleotide polymorphisms (SNPs) of the TNIP1 gene, namely rs3805435, rs3792798, rs3792797, rs869976, rs17728338, and rs999011 were genotyped by using polymerase chain reaction-ligase detection reaction. Statistical analyses were performed using the PLINK 1.07 package. Allele frequencies and genotyping frequencies for six SNPs were compared by using Chi-square test, odd ratio (OR) (including 95% confidence interval) were calculated. The haplotype analysis was conducted by Haploview software. RESULTS: The frequencies of alleles of five SNPs were significantly different between the GPP group and the control group (P <= 7.22 * 10-3), especially in the GPP patients without psoriasis vulgaris (PsV). In the haplotype analysis, the most significantly different haplotype was H4: ACGAAC, with 13.1% frequency in the GPP group but only 3.4% in the control group (OR = 4.16, P = 4.459 * 10-7). However, no significant difference in the allele frequencies was found between the PPP group and control group for each of the six SNPs (P > 0.05). CONCLUSIONS: Polymorphisms in TNIP1 are associated with GPP in Chinese Han population. However, no association with PPP was found. These findings suggest that TNIP1 might be a susceptibility gene for GPP. PMID- 27364787 TI - Types of Organ Involvement in Patients with Immunoglobulin G4-related Disease. AB - BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized systemic disease that can involve multiple organs and various clinical phenotypes. The purpose of this study was to analyze different types of organ involvement in IgG4-RD patients in China. METHODS: We conducted a prospective cohort study on IgG4-RD patients to analyze the clinical manifestations and rare features of IgG4-RD. Patients were grouped into different types according to organ involvement regarding organ number and organ site. The constituent ratio in different types was also analyzed. RESULTS: A total of 200 IgG4-RD patients, with a male:female ratio of 2.08:1, were grouped into different types. Cases having involvement of two or three organs were the most common whereas the fewest number of patients had multi-organ (>=4) involvement. Serum IgG4 and IgE levels, IgG4/IgG ratio, and percentage of eosinophils increased as the number of involved organs increased. In addition, constituent ratio analysis revealed that patients with salivary gland/lacrimal gland swelling, who also constituted the largest number of IgG4-RD patients, had higher serum IgG4 concentrations and IgG4/IgG values, had higher percentage of Eos, and were more likely to have had a history of allergies relative to patients with internal organ involvement. CONCLUSIONS: The characteristic feature of IgG4-RD is multiple organ involvement with various clinical manifestations and different types. Although serum IgG4 levels increased with the number of involved organs, serum IgG4 levels were higher for those patients with salivary gland/lacrimal gland swelling compared with those with internal organ involvement. Thus, valuable clues to the differential diagnosis of IgG4-RD could be obtained by examining the clinical patterns of organ involvement. PMID- 27364788 TI - "Onion Skin-liked Sign" in Thyroid Ultrasonography: A Characteristic Feature of Benign Thyroid Nodules. AB - BACKGROUND: Some ultrasonographic (US) signs overlap between benign and malignant nodules. The purpose of this study was to raise a special US sign of benign thyroid nodules, termed the "onion skin-liked sign." METHODS: Twenty-seven patients with 27 nodules who shrank naturally and the "onion skin-liked sign" appeared on the final US images were enrolled in the study. The ultrasound characters and risk stratifications at the start and end of observation were compared. Then, thirty goiters with fibrosis and thirty papillary thyroid carcinomas (PTC) were randomly selected from the database of our hospital, matched the sizes of 27 nodules at the end point of observation. The differences of "onion skin-liked sign" between the two groups were analyzed. RESULTS: The average duration of follow-up of 27 nodules was 24.0 +/- 12.2 months (range, 12 65 months). At the end of the follow-up, the size of the nodules decreased on average by 1.26 +/- 0.82 cm (range, 0.3-3.4 cm) and calcification was found in 21 nodules, compared with only 2 nodules with calcification at the start of the follow-up. In addition, only negligible or no blood flow signal could be detected at the periphery of all the nodules and 100% (27/27) were high suspicion at the end of observation. In matched groups, all PTC showed high suspicion of malignancy, 18/30 (60%) goiters with fibrosis were high suspicion and 11/30 (37%) were intermediate suspicion. Twenty-two patients in the group of nodular fibrosis presented "onion skin-liked sign," which was not shown in any patient of PTC group. The sensitivity, specificity, positive predictive value, and negative predictive value of "onion skin-liked sign" in predicting nodular goiter with fibrosis were 73.3%, 100%, 100%, and 78.9%, respectively. CONCLUSIONS: The "onion skin-liked sign" was a characteristic US feature of benign thyroid nodules detected in the follow-up of thyroid nodules. It is useful to differentiate PTCs and nodular goiters with fibrosis. PMID- 27364789 TI - Intravascular Ultrasound Classification of Plaque in Angiographic True Bifurcation Lesions of the Left Main Coronary Artery. AB - BACKGROUND: Accurately, characterizing plaques is critical for selecting the optimal intervention strategy for the left main coronary artery (LMCA) bifurcation. Coronary angiography cannot precisely assess the location or nature of plaques in bifurcation lesions. Few intravascular ultrasound (IVUS) classification scheme has been reported for angiographic imaging of true bifurcation lesions of the unprotected LMCA thus far. In addition, the plaque composition at the bifurcation has not been elucidated. This study aimed to detect plaque composition at LMCA bifurcation lesions by IVUS. METHODS: Fifty eight patients were recruited. The location, concentricity or eccentricity, site of maximum thickness, and composition of plaques of the distal LMCA, ostial left anterior descending (LAD) coronary artery and, left circumflex (LCX) coronary artery were assessed using IVUS and described using illustrative diagrams. RESULTS: True bifurcation lesions of the unprotected LMCA were classified into four types: Type A, with continuous involvement from the distal LMCA to the ostial LAD and the ostial LCX with eccentric plaques; Type B, with concentric plaques at the distal LMCA, eccentric plaques at the ostial LAD, and no plaques at the LCX; Type C, with continuous involvement from the distal LMCA to the ostial LCX, with eccentric plaques, and to the ostial LAD, with eccentric plaques; and Type D, with continuous involvement from the distal LMCA to the ostial LAD, with eccentric plaques, and to the ostial LCX, with concentric plaques. The carina was involved in only 3.5% of the plaques. A total of 51.7% of the plaques at the ostium of the LAD were soft, while 44.8% and 44.6% were fibrous in the distal LMCA and in the ostial LCX, respectively. CONCLUSIONS: We classified LMCA true bifurcation lesions into four types. The carina was always free from disease. Plaques at the ostial LAD tended to be soft, whereas those at the ostial LCX and the distal LMCA tended to be fibrous. PMID- 27364790 TI - Downregulation of Notch-regulated Ankyrin Repeat Protein Exerts Antitumor Activities against Growth of Thyroid Cancer. AB - BACKGROUND: The Notch-regulated ankyrin repeat protein (NRARP) is recently found to promote proliferation of breast cancer cells. The role of NRARP in carcinogenesis deserves extensive investigations. This study attempted to investigate the expression of NRARP in thyroid cancer tissues and assess the influence of NRARP on cell proliferation, apoptosis, cell cycle, and invasion in thyroid cancer. METHODS: Thirty-four cases with thyroid cancer were collected from the Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between 2011 and 2012. Immunohistochemistry was used to detect the level of NRARP in cancer tissues. Lentivirus carrying NRARP shRNA (Lenti-NRARP-shRNA) was applied to down-regulate NRARP expression. Cell viability was tested after treatment with Lenti-NRARP-shRNA using 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle distribution were determined by flow cytometry. Cell invasion was tested using Transwell invasion assay. In addition, expressions of several cell cycle associated and apoptosis-associated proteins were examined using Western blotting after transfection. Student's t-test, one-way analysis of variance (ANOVA), or Kaplan-Meier were used to analyze the differences between two group or three groups. RESULTS: NRARP was highly expressed in thyroid cancer tissues. Lenti NRARP-shRNA showed significantly inhibitory activities against cell growth at a multiplicity of infection of 10 or higher (P < 0.05). Lenti-NRARP-shRNA-induced G1 arrest (BHT101: 72.57% +/- 5.32%; 8305C: 75.45% +/- 5.26%) by promoting p21 expression, induced apoptosis by promoting bax expression and suppressing bcl-2 expression, and inhibited cell invasion by suppressing matrix metalloproteinase-9 expression. CONCLUSION: Downregulation of NRARP expression exerts significant antitumor activities against cell growth and invasion of thyroid cancer, that suggests a potential role of NRARP in thyroid cancer targeted therapy. PMID- 27364791 TI - Characteristics of Agraphia in Chinese Patients with Alzheimer's Disease and Amnestic Mild Cognitive Impairment. AB - BACKGROUND: Patients with Alzheimer's disease (AD) manifest progressive decline in writing abilities. Most studies on agraphia in AD have been performed in the alphabetic system, such as English. However, these findings may not be applicable to other written language systems. The unique features of the Chinese written script could affect the patterns of agraphia in Chinese AD patients. The aim of this study was to explore the features of writing errors in Chinese patients with AD and amnestic mild cognitive impairment (a-MCI), as well as to study the relationship between their writing errors and neuropsychological functions. METHODS: In this study, we performed an observational study in a group of subjects including 17 AD patients, 14 patients with a-MCI, and 16 elderly healthy controls. We analyzed the writing errors in these subjects and also studied the relationship between their writing errors and neuropsychological functions. RESULTS: Our study showed that in patients whose mother tongue is Chinese, writing ability was comparatively well preserved in the MCI phase but significantly impaired when the disease progressed to the stage of AD. The writing errors showed corresponding increase with the severity of cognition decline, both in the types of errors and rate of occurrence. Analysis of the writing errors showed that word substitution and unintelligible words were the most frequent error types that occurred in all the three study groups. The occurrence rate of unintelligible words was significantly higher in the AD group compared with the a-MCI group (P = 0.024) and control group (P = 0.018). In addition, the occurrence rates of word substitution were also significantly higher in AD (P = 0.013) and a-MCI groups (P = 0.037) than that of control group. However, errors such as totally no response, visuospatial impairment, paragraph agraphia, ideograph, and perseverative writing errors were only seen in AD group. Besides, we also found a high occurrence rate of visuoconstructional errors (13.3%) in our AD group. CONCLUSIONS: Our study confirmed that agraphia is an important feature in patients with AD. The writing error profile in patients whose native language is Chinese was unique compared to patients using the alphabetic language system. PMID- 27364792 TI - Frontolateral Approach Applied to Sellar Region Lesions: A Retrospective Study in 79 Patients. AB - BACKGROUND: Various surgical approaches for the removal of sellar region lesions have previously been described. This study aimed to evaluate the reliability and safety of the frontolateral approach (FLA) to remove sellar region lesions. METHODS: We presented a retrospective study of 79 patients with sellar region lesions who were admitted and operated by the FLA approach from August 2011 to August 2015 in Department of Neurosurgery of Beijing Tian Tan Hospital. We classified FLA into three types, compared the FLA types to the areas of lesion invasion, and analyzed operation bleeding volume, gross total resection (GTR) rate, visual outcome, and mortality. RESULTS: Seventy-nine patients were followed up from 2.9 to 50.3 months with a mean follow-up of 20.5 months. There were 42 cases of meningiomas, 25 cases of craniopharyngiomas, and 12 cases of pituitary adenomas. The mean follow-up Karnofsky Performance Scale was 90.4. GTR was achieved in 75 patients (94.9%). Two patients (2.5%) had tumor recurrence. No patients died perioperatively or during short-term follow-up. Three patients (3.8%) with craniopharyngioma died 10, 12, and 23 months, respectively, after surgery. The operative bleeding volume of this study was no more than that of the other approaches in the sellar region (P = 0.783). In this study, 35 patients (44.3%) had visual improvement after surgery, 38 patients (48.1%) remained unchanged, and three patients' visual outcome (3.8%) worsened. CONCLUSIONS: FLA was an effective approach in the treatment of sellar region lesions with good preservation of visual function. FLA classification enabled tailored craniotomies for each patient according to the anatomic site of tumor invasion. This study found that FLA had similar outcomes to other surgical approaches of sellar region lesions. PMID- 27364793 TI - A Polysomnography Study of Kleine-Levin Syndrome in a Single Center. AB - BACKGROUND: Kleine-Levin syndrome (KLS) is a rare sleep disorder characterized by recurrent episodes of hypersomnia. Polysomnographic (PSG) researches of KLS have been reported only in few publications in the past decades. This study aimed to investigate the characteristics of PSG of KLS. METHODS: This study, which was conducted from March 2010 to July 2014, included seven patients diagnosed with KLS in the Sleep and Wake Disorder Center of Huashan Hospital, Fudan University (Shanghai, China). PSG and multiple sleep latency tests (MSLT) were performed during their episodes and the results were evaluated. RESULTS: Five of the seven patients were males. The mean age at KLS onset was 15.6 +/- 3.6 years. The number of episodes ranged from 2 to 7. The duration of episodes lasted from 4 to 11 days. The sleep architecture and proportion were normal in most of the patients. The average value of mean sleep latency was 6.9 +/- 4.1 min. No sleep-onset rapid eye movement (SOREM) was detected in three of the patients, whereas one patient experienced one period of SOREM, and such episodes occurred twice in other two patients. CONCLUSIONS: We found that sleep architecture and proportion were normal in most KLS patients. However, the results of PSG and MSLT had no specificity for KLS patients. PMID- 27364794 TI - Study of Cardiac Arrest Caused by Acute Pulmonary Thromboembolism and Thrombolytic Resuscitation in a Porcine Model. AB - BACKGROUND: The success rate of resuscitation in cardiac arrest (CA) caused by pulmonary thromboembolism (PTE) is low. Furthermore, there are no large animal models that simulate clinical CA. The aim of this study was to establish a porcine CA model caused by PTE and to investigate the pathophysiology of CA and postresuscitation. METHODS: This model was induced in castrated male pigs (30 +/- 2 kg; n = 21) by injecting thrombi (10-15 ml) via the left external jugular vein. Computed tomographic pulmonary angiography (CTPA) was performed at baseline, CA, and return of spontaneous circulation (ROSC). After CTPA during CA, cardiopulmonary resuscitation (CPR) with thrombolysis (recombinant tissue plasminogen activator 50 mg) was initiated. Hemodynamic, respiratory, and blood gas data were monitored. Cardiac troponins T, cardiac troponin I, creatine kinase MB, myoglobin, and brain natriuretic peptide (BNP) were measured by enzyme-linked immunosorbent assay. Data were compared between baseline and CA with paired sample t-test and compared among different time points for survival animals with repeated measures analysis of variance. RESULTS: Seventeen animals achieved CA after emboli injection, while four achieved CA after 5-8 ml more thrombi. Nine animals survived 6 h after CPR. CTPA showed obstruction of the pulmonary arteries. Mean aortic pressure data showed occurrence of CA caused by PTE (Z = 2.803, P = 0.002). The maximal rate of mean increase of left ventricular pressure (dp/dtmax) was statistically decreased (t = 6.315, P = 0.000, variation coefficient = 0.25), and end-tidal carbon dioxide partial pressure (PetCO2) decreased to the lowest value (t = 27.240, P = 0.000). After ROSC (n = 9), heart rate (HR) and mean right ventricular pressure (MRVP) remained different versus baseline until 2 h after ROSC (HR, P = 0.036; MRVP, P = 0.027). Myoglobin was statistically increased from CA to 1 h after ROSC (P = 0.036, 0.026, 0.009, respectively), and BNP was increased from 2 h to 6 h after ROSC (P = 0.012, 0.014, 0.039, respectively). CONCLUSIONS: We established a porcine model of CA caused by PTE. The dp/dtmaxand PetCO2may be important for the occurrence of CA, while MRVP may be more important in postresuscitation. PMID- 27364795 TI - Effect of Splenic Regulatory T-cell Apoptosis on the Postresuscitation Immune Dysfunction in a Porcine Model. AB - BACKGROUND: Postresuscitation immune dysfunction contributes to the low survival rate after successful resuscitation, but its mechanism remains poorly understood. The purpose of this study was to investigate whether splenic regulatory T-cell (Treg) apoptosis was involved in the postresuscitation immune dysfunction. METHODS: Thirty-eight pigs were randomly divided into sham-operated group (SHAM group, n = 8), 12 h post return of spontaneous circulation (ROSC) group, 24 h post-ROSC group, and 48 h post-ROSC group (n = 10 per group). A Wuzhishan miniature porcine model of 8-min ventricular fibrillation cardiac arrest (CA) was established. The apoptosis rates of Treg in the spleen were tested by flow cytometry; the expressions of forkhead/winged helix transcription factor (Foxp3) of Treg in the spleen were detected by real-time polymerase chain reaction; and the levels of interleukin-4 (IL-4), IL-10, and interferon gamma (IFN-gamma) of Treg in the spleen were detected by enzyme-linked immunosorbent assay. RESULTS: The apoptosis rates of Treg in all post-ROSC groups were significantly lower than that of SHAM group (7.7% +/- 1.9%, 7.1% +/- 1.8%, 6.2% +/- 0.4% vs. 13.1% +/- 1.6%; P < 0.05); the expression levels of Foxp3 and IL-10 were also decreased with the increase of apoptosis rates of Treg. Helper T-cells CD4+ lymphocyte subsets were significantly lower in the post-ROSC groups compared with SHAM group (29.1% +/- 2.2%, 24.3% +/- 2.2%, 24.1% +/- 2.5% vs. 43.8% +/- 4.5%; P < 0.01) at 12, 24, and 48 h after ROSC. Compared with SHAM group, the levels of IFN-gamma (161.0 +/- 12.9, 167.7 +/- 10.5, 191.2 +/- 7.7 vs. 7.6 +/- 0.9 ng/L) and IL-4 (27.7 +/- 6.2, 35.9 +/- 3.5, 50.6 +/- 6.1 vs. 13.3 +/- 2.3 ng/L) and the ratio of IFN-gamma/IL-4 (8.6 +/- 2.3, 4.9 +/- 0.4, 4.5 +/- 0.9 vs. 0.8 +/- 0.2) were all greatly elevated in all post-ROSC groups (P < 0.05). CONCLUSIONS: Apoptosis rate of Treg was significantly decreased after CA, and thus the proportion of Treg was increased and the inhibitory effects were enhanced, which further led to the decrease of the amount of CD4+ T-cells. In addition, the T helper type 2/T helper type 1 (Th2/Th1) cell drift of Treg in the spleen caused postresuscitation immune dysfunction. PMID- 27364796 TI - Magnetic Resonance Three-dimensional Cube Technique in the Measurement of Piglet Femoral Anteversion. AB - BACKGROUND: The accurate measurement of the femoral anteversion (FA) angle is always a topic of much debate in the orthopedic surgery and radiology research. We aimed to explore a new FA measurement method to acquire accurate results without radiation damage using piglet model. METHODS: A total of thirty piglets were assigned to two groups based on the age. Bilateral femora were imaged with 3.0-T magnetic resonance (MR) and 64-slice computed tomography (CT) examinations on all piglets. FA was measured on MR-three-dimensional (3D) postprocessing software with a four-step method: initial validation of the femoral condylar axis, validation of the condylar plane, validation of the femoral neck axis, and line-plane angle measurement of FA. After MR and CT examinations, all piglets were sacrificed and their degree of FA was measured using their excised, dried femora. MR, CT, and dried-femur measurement results were analyzed statistically; MR and CT measurements were compared for accuracy against each other and against the gold standard dried femur measurement. RESULTS: In both groups, the mean FA value measured by MR was lower than that measured by CT. A statistically significant difference was observed between CT- and dried-femur measurements but not between MR- and dried-femur measurements. A higher correlation (0.783 vs. 0.408) and a higher consistency (0.863 vs. 0.578) with dried-femur measurement results were seen for MR measurements than CT measurements in the 1-week age group. However, in the 8-week age group, similar correlations (0.707 vs. 0.669) and consistencies (0.864 vs. 0.821) were observed. CONCLUSIONS: Noninvasive MR-3D Cube reconstruction was able to accurately measure FA in piglets. Particularly in the 1-week age group with a larger proportion of cartilaginous structures, the correlation and consistency between MR- and dried-femur measurement results were higher than those between CT- and dried-femur measurements, suggesting that MR may be a new useful examination tool for FA-related diseases in children. PMID- 27364797 TI - Migration of Adipose-derived Mesenchymal Stem Cells Stably Expressing Chondroitinase ABC In vitro. AB - BACKGROUND: Several studies have revealed that adipose-derived mesenchymal stem cells (ADSCs) can be used as seed cells for the treatment of spinal cord injury (SCI). Chondroitinase ABC (ChABC) decomposes chondroitin sulfate proteoglycans in the glial scar that forms following SCI, allowing stem cells to penetrate through the scar and promote recovery of nerve function. This study aimed to establish ADSCs that stably express ChABC (ChABC-ADSCs) and evaluate the migratory capability of ChABC-ADSCs in vitro. METHODS: ADSCs were obtained from Sprague Dawley rats using secondary collagenase digestion. Their phenotypes were characterized using flow cytometry detection of cell surface antigens and their stem cell properties were confirmed by induction of differentiation. After successful culture, ADSCs were transfected with lentiviral vectors and ChABC ADSCs were obtained. Proliferation curves of ChABC-ADSCs were determined using the Cell Counting Kit-8 method, ChABC expression was verified using Western blotting, and the migration of ChABC-ADSCs was analyzed using the transwell assay. RESULTS: Secondary collagenase digestion increased the isolation efficiency of primary ADSCs. Following transfection using lentiviral vectors, the proliferation of ChABC-ADSCs was reduced in comparison with control ADSCs at 48 h (P < 0.05). And the level of ChABC expression in the ChABC-ADSC group was significantly higher than that of the ADSC group (P < 0.05). Moreover, ChABC-ADSC migration in matrigel was significantly enhanced in comparison with the control (P < 0.05). CONCLUSIONS: Secondary collagenase digestion can be used to effectively isolate ADSCs. ChABC-ADSCs constructed using lentiviral vector transfection stably express ChABC, and ChABC expression significantly enhances the migratory capacity of ADSCs. PMID- 27364798 TI - Effects of Low-dose Triamcinolone Acetonide on Rat Retinal Progenitor Cells under Hypoxia Condition. AB - BACKGROUND: Retinal degenerative diseases are the leading causes of blindness in developed world. Retinal progenitor cells (RPCs) play a key role in retina restoration. Triamcinolone acetonide (TA) is widely used for the treatment of retinal degenerative diseases. In this study, we investigated the role of TA on RPCs in hypoxia condition. METHODS: RPCs were primary cultured and identified by immunofluorescence staining. Cells were cultured under normoxia, hypoxia 6 h, and hypoxia 6 h with TA treatment conditions. For the TA treatment groups, after being cultured under hypoxia condition for 6 h, RPCs were treated with different concentrations of TA for 48-72 h. Cell viability was measured by cell counting kit-8 (CCK-8) assay. Cell cycle was detected by flow cytometry. Western blotting was employed to examine the expression of cyclin D1, Akt, p-Akt, nuclear factor (NF)-kappaB p65, and caspase-3. RESULTS: CCK-8 assays indicated that the viability of RPCs treated with 0.01 mg/ml TA in hypoxia group was improved after 48 h, comparing with control group (P < 0.05). After 72 h, the cell viability was enhanced in both 0.01 mg/ml and 0.02 mg/ml TA groups compared with control group (all P < 0.05). Flow cytometry revealed that there were more cells in S-phase in hypoxia 6 h group than in normoxia control group (P < 0.05). RPCs in S and G2/M phases decreased in groups given TA, comparing with other groups (all P < 0.05). There was no significant difference in the total Akt protein expression among different groups, whereas upregulation of p-Akt and NF-kappaB p65 protein expression and downregulation of caspase-3 and cyclin D1 protein expression were observed in 0.01 mg/ml TA group, comparing with hypoxia 6 h group and control group (all P < 0.05). CONCLUSION: Low-dose TA has anti-apoptosis effect on RPCs while it has no stimulatory effect on cell proliferation. PMID- 27364799 TI - Endobronchial Ultrasound-guided Transbronchial Needle Aspiration versus Standard Bronchoscopic Modalities for Diagnosis of Sarcoidosis: A Meta-analysis. AB - BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an effective technique used to precisely detect enlarged mediastinal lymph nodes. The efficacy of EBUS-TBNA versus standard modalities for the diagnosis of sarcoidosis remains to be elucidated. In this meta-analysis, we compared the efficacies of these methods. METHODS: We searched PubMed, Embase, The Cochrane Library, Wanfang, Cpvip, CNKI, and the bibliographies of the relevant references. We analyzed the data obtained with Revman 5.2 (Nordic Cochrane Center, Copenhagen, Denmark) and Stata 12.0 software (Stata Corporation, College Station, TX, USA). The Mantel-Haenszel method was used to calculate the pooled odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: Sixteen studies with a total of 1823 participants met the inclusion criteria, and data were extracted regarding the diagnostic yield of each approach. The ORs for EBUS TBNA versus transbronchial lung biopsy (TBLB) for the diagnosis of sarcoidosis ranged from 0.26 to 126.58, and the pooled OR was 5.89 (95% CI, 2.20-15.79, P = 0.0004). These findings indicated that EBUS-TBNA provided a much higher diagnostic yield than TBLB. The pooled OR for EBUS-TBNA + TBLB + endobronchial biopsy (EBB) versus TBNA + TBLB + EBB was 1.54 (95% CI, 0.61-3.93, P = 0.36), implying that there was no significant difference between their diagnostic yields. However, clinical heterogeneity was reflected in the nature of the studies and in the operative variables. CONCLUSIONS: The results of this meta analysis suggest that EBUS-TBNA + TBLB + EBB could be used for the diagnosis of sarcoidosis, if available. At medical centers without EBUS-TBNA, TBNA + TBLB + EBB could be used instead. PMID- 27364800 TI - Perioperative Evaluation of Cerebral Blood Flow Using (123)I-labeled N-isopropyl p-iodoamphetamine Single-Photon Emission Computed Tomography without Blood Sampling in Patients Who Underwent Carotid Artery Stenting. PMID- 27364801 TI - Internal Pallidum and Subthalamic Nucleus Deep Brain Stimulation for Oromandibular Dystonia. PMID- 27364802 TI - Error Analysis and Some Suggestions on Animal Stereotactic Experiment from Inaccuracy of Rhesus Macaques Atlas. PMID- 27364803 TI - Primary Torsion of Lesser Omentum Presented with Acute Abdomen and Successfully Managed with Laparoscopic Surgery. PMID- 27364804 TI - Primary Paraganglioma of Seminal Vesicle. PMID- 27364805 TI - Structure-editing: A New Branch? PMID- 27364806 TI - Self-reported Barriers to Adherence and Persistence to Treatment With Injectable Medications for Type 2 Diabetes. AB - PURPOSE: This study explored the barriers that adult Americans experience when taking injectable medications for type 2 diabetes, from the time of filling the initial prescription through the decision to discontinue the medication. METHODS: An Internet-based survey was conducted in 2 waves among adult patients (N = 2000) who had received a physician prescription for insulin, liraglutide, or exenatide once weekly (QW), regardless of whether the prescription was filled by a pharmacy. In wave 1, patients were surveyed on their medication history and experience and, if relevant, the medication discontinuation process. Those still taking their injectable medication at the time of wave 1 were contacted 6 months later (wave 2, n = 585) to assess any changes in their medication experience. FINDINGS: Among patients who delayed filling their prescription by >=1 week, cost was a common reason for delay for refilling of liraglutide (63%) and exenatide QW (49%). The most commonly reported barrier to maintaining injectable medication was injection concerns (42%) such as aversion to needles, pain, or needle size. Lack of perceived need was the most common reason for discontinuation for basal (47%) and prandial/premixed (44%) insulin. For liraglutide, the most common reason for discontinuation was experiencing an adverse event (33%); for exenatide QW, it was injection concerns (38%). IMPLICATIONS: The diverse barriers we identified underscore the need for better patient-prescriber communication to ensure that newly prescribed injectable medications are consistent with a patient's ability or willingness to manage them, to appropriately set expectations about medications, and to address new barriers that arise during the course of treatment. PMID- 27364807 TI - Exposure Matching of Pediatric Anti-infective Drugs: Review of Drugs Submitted to the Food and Drug Administration for Pediatric Approval. AB - PURPOSE: Over the last decade, few new antibiotics have been approved by the Food and Drug Administration (FDA) for pediatric use. For most anti-infective agents, including antibiotics, extrapolation of efficacy from adults to children is possible if the disease and therapeutic exposures are similar between the 2 populations. This approach reduces the number of studies required in children, but relies heavily on exposure matching between children and adults. Failures in exposure matching can lead to delays in pediatric approvals of new anti-infective agents. We sought to determine the extent of exposure matching, defined by a comparison of area under the concentration-time curve, between children and adults, for anti-infective drug products submitted to the FDA for approval. METHODS: We reviewed anti-infective submissions to the FDA (2002-2014) for pediatric indication. We included drug products administered via oral, intravenous, or intramuscular administration routes, and those with AUC estimates for children in available FDA reports. Our main outcome of interest was the proportion of drugs with median (or mean) pediatric AUC within 20% of the median (or mean) reported adult value. FINDINGS: We identified 29 drug products that met inclusion criteria, 14 (48%) of which had mean (or median) AUCs of all submitted age groups within 20% of that in adults. Only route of administration and drug class were associated with pediatric AUC within 20% of adult AUC. IMPLICATIONS: Future research is needed to define criteria for and predictors of successful exposure matching of anti-infectives between children and adults. PMID- 27364808 TI - Collaborative Care for Depression in Chronic Hepatitis C Clinics. AB - OBJECTIVE: Depression is highly prevalent yet underdiagnosed and undertreated among patients with chronic hepatitis C virus (HCV) infection. Collaborative care models have improved depression outcomes in primary care settings, and this study aimed to provide more information on testing such methods in specialty HCV care. METHODS: Hepatitis C Translating Initiatives for Depression Into Effective Solutions (HEPTIDES) was a randomized controlled trial that tested a collaborative depression care model in HCV clinics at four Veterans Affairs facilities. The HEPTIDES intervention consisted of an offsite depression care team (depression care manager, pharmacist, and psychiatrist) that delivered collaborative care. Participant interview data were collected at baseline and at six months. The outcome was depression severity measured with the Hopkins Symptom Checklist (SCL-20) and reported as treatment response (>=50% decrease in SCL-20 item score), remission (mean SCL-20 item score <.5), and depression-free days (DFDs). RESULTS: Baseline screening identified 263 HCV-infected patients with depression. In unadjusted analyses, intervention participants' reports trended toward more treatment response (19% versus 13%) and remission (12% versus 6%), but total number of DFDs (50.9) was similar to that of usual care participants (50.7). These trends did not reach statistical significance for the overall sample in the adjusted analyses: response (odds ratio [OR]=2.02, 95% confidence interval [CI]=.98-4.20), remission (OR=2.63, CI=1.00-6.94), and DFDs (beta=7.6 days, CI=-.99 to 16.2). However, the intervention was effective in improving all three outcomes for patients who did not meet criteria for remission at baseline (SCL-20 score >.5, N=245). CONCLUSIONS: Depression collaborative care resulted in modest improvements in HCV patient depression outcomes. Future research should investigate intervention modifications to improve outcomes in specialty HCV clinics. PMID- 27364809 TI - Correlates of Length of Stay and Boarding in Florida Emergency Departments for Patients With Psychiatric Diagnoses. AB - OBJECTIVE: Length of stay (LOS) and boarding in the emergency department (ED) for psychiatric patients have been the subject of concern, given the problems with crowding and excessive wait times in EDs. This investigation examined correlates of LOS and boarding in Florida EDs for patients presenting with psychiatric complaints from 2010 to 2013. METHODS: Utilizing the Florida ED discharge database, the authors examined the association of LOS and boarding with hospital and encounter factors for adult patients presenting with a primary psychiatric diagnosis (N=597,541). RESULTS: The mean LOS was 7.77 hours. Anxiety disorders were the most frequent psychiatric complaint and were associated with the lowest mean LOS compared with other diagnoses (p<.05). Patient encounters resulting in a presentation of intentional self-harm and suicidality or schizophrenia were associated with significantly longer stays compared with other psychiatric diagnoses. Commercial insurance was associated with the shortest average LOS. African Americans, Hispanics, and patients age 45 and older were associated with a longer average LOS. Smaller hospital size, for-profit ownership, and rural designation were associated with a shorter average LOS. Teaching status was not associated with LOS. Furthermore, 73% of encounters resulting in transfers qualified as episodes of boarding (a stay of more than six or more hours in the ED). CONCLUSIONS: Extended LOS was endemic for psychiatric patients in Florida EDs. PMID- 27364810 TI - Stigma by Any Other Name. AB - OBJECTIVE: Some advocates argue that the word "stigma" is itself stigmatizing and contributes to further denigration of people with mental illness. This brief report presents results of a nationwide survey comparing terminology related to stigma in regard to mental illness. METHODS: A total of 340 Amazon Mechanical Turk survey takers read variations of a vignette depicting an individual with schizophrenia and then completed a brief stigma measure. The vignette varied in a single sentence in which three different words-"stigma," "prejudice," and "reactions"-were used to describe coworkers' possible attitudes toward the depicted individual. RESULTS: Stigma ratings did not differ by vignette group. "Reactions" was viewed as significantly less disrespectful than both "stigma" and "prejudice" (p<.001). CONCLUSIONS: Further research is needed to support replacing the word "stigma" in public arenas. Current efforts to remove the word may unnecessarily distract advocates and policy makers from the primary mission of erasing stigma. PMID- 27364811 TI - Prevalence and Predictors of Obesity-Related Counseling Provided by Outpatient Psychiatrists in the United States. AB - OBJECTIVE: This study sought to identify rates and predictors of obesity counseling performed by outpatient psychiatrists in the United States. METHODS: The 2005-2010 National Ambulatory Medical Care Surveys provided data from 7,309 outpatient psychiatry visits. Logistic regression was used to examine associations between patient, visit, and practice characteristics and outcomes. RESULTS: Most (81%) visits occurred in a private practice setting. Nine percent (N=657) of visits included measurement of patient body mass index (BMI); 30% of these visits were with patients who met the obesity criterion (BMI >=30.0 kg/m2). Among visits with obese patients, 16% included exercise counseling, 22% included weight reduction counseling, and 24% included diet or nutrition counseling. Patients with obesity were more likely than patients without obesity to receive diet or nutrition counseling (p<.05) and weight reduction counseling (p<.05), but not exercise counseling. Black patients were significantly less likely to receive any form of counseling (p<.05). CONCLUSIONS: There is a significant need to improve psychiatrists' obesity counseling. PMID- 27364812 TI - General Medical Outcomes From the Primary and Behavioral Health Care Integration Grant Program. AB - OBJECTIVE: Primary and Behavioral Health Care Integration (PBHCI) grants aim to improve the health of people with serious mental illness by integrating primary and preventive general medical services into behavioral health settings. This report describes the general medical outcomes of persons served by early cohorts of programs, funded in 2009 or 2010, that participated in this national demonstration project. METHODS: A quasi-experimental, difference-in-differences design was used to compare changes in general medical health among consumers served at three PBHCI clinics (N=322) and three clinics that were selected as matched control sites (N=469). Propensity-score weighting was used to adjust for baseline differences between PBHCI and control clinic populations. Baseline data were collected between 2010 and 2012; follow-up data were collected approximately one year later. General medical outcomes included blood pressure; body mass index; cholesterol, triglyceride, and blood glucose or HbA1c levels; and self reported tobacco smoking. RESULTS: Compared with consumers served at control clinics, PBHCI consumers had better outcomes for cholesterol: mean reductions in total cholesterol were greater by 36 mg/dL (p<.01), mean reductions in low density lipoprotein cholesterol were greater by 35 mg/dL (p<.001), and mean increases in high-density lipoprotein cholesterol were greater by 3 mg/dL (p<.05). No significant PBHCI effects were observed for the other health indicators. CONCLUSIONS: Approximately one year of PBHCI treatment resulted in statistically and potentially clinically significant improvements in cholesterol but not in other general medical outcomes examined. More rigorous implementation of integrated care in community behavioral health settings may be needed to further improve the health of adults with serious mental illness. PMID- 27364813 TI - Use of Mental Health Care and Unmet Needs for Health Care Among Lesbian and Bisexual Chinese-, Korean-, and Vietnamese-American Women. AB - OBJECTIVE: This study examined associations between sexual orientation of Asian American women and receipt of mental health care and unmet need for health care. METHODS: Computer-assisted self-interviews were conducted with 701 unmarried Chinese-, Korean-, and Vietnamese-American women ages 18 to 35. Multivariate regression models examined whether lesbian and bisexual participants differed from exclusively heterosexual participants in use of mental health care and unmet need for health care. RESULTS: After the analyses controlled for mental health status and other covariates, lesbian and bisexual women were more likely than exclusively heterosexual women to have received any past-year mental health services and reported a greater unmet need for health care. Sexual-minority women were no more likely to have received minimally adequate care. CONCLUSIONS: Given the high rates of mental health problems among Asian-American sexual-minority women, efforts are needed to identify and overcome barriers to receipt of adequate mental health care and minimize unmet health care needs. PMID- 27364814 TI - Seclusion Reduction in Dutch Mental Health Care: Did Hospitals Meet Goals? AB - OBJECTIVE: In 2006, a goal of reducing seclusion in Dutch hospitals by at least 10% each year was set. More than 100 reduction projects in 55 hospitals have been conducted, with ?35 million in funding. This study evaluated the results. METHODS: Data (2008 to 2013) were from a national register. Multilevel logistic regression examined determinants of seclusion. RESULTS: Hospital participation in the register ranged from eight in 2008 to 66 in 2013, and admissions ranged from 11,300 to 113,290. The average yearly nationwide reduction of secluded patients was about 9%. Reduction was achieved in half of the hospitals. Some hospitals saw increased rates. In some hospitals where seclusion decreased, use of forced medication increased. Higher seclusion rates were associated with psychotic and bipolar disorders, male gender, and several ward types. CONCLUSIONS: Seclusion decreased significantly, and forced medication increased. Rates varied widely between hospitals. For many hospitals, more efforts to reduce seclusion are needed. PMID- 27364815 TI - Integrating Primary Care Into Community Mental Health Centers: Impact on Utilization and Costs of Health Care. AB - OBJECTIVE: This evaluation was designed to assess the impact of providing integrated primary and mental health care on utilization and costs for outpatient medical, inpatient hospital, and emergency department treatment among persons with serious mental illness. METHODS: Two safety-net, community mental health centers that received a Substance Abuse and Mental Health Services Administration Primary and Behavioral Health Care Integration (PBHCI) grant were the focus of this study. Clinic 1 had a ten-year history of providing integrated services whereas clinic 2 began integrated services with the PBHCI grant. Difference-in differences (DID) analyses were used to compare individuals enrolled in the PBHCI programs (N=373, clinic 1; N=389, clinic 2) with propensity score-matched comparison groups of equal size at each site by using data obtained from medical records. RESULTS: Relative to the comparison groups, a higher proportion of PBHCI clients used outpatient medical services at both sites following program enrollment (p<.003, clinic 1; p<.001, clinic 2). At clinic 1, PBHCI was also associated with a reduction in the proportion of clients with an inpatient hospital admission (p=.04) and a trend for a reduction in inpatient hospital costs per member per month of $217.68 (p=.06). Hospital-related cost savings were not observed for PBHCI clients at clinic 2 nor were there significant differences between emergency department use or costs for PBHCI and comparison groups at either clinic. CONCLUSIONS: Investments in PBHCI can improve access to outpatient medical care for persons with severe mental illness and may also curb hospitalizations and associated costs in more established programs. PMID- 27364816 TI - The RAISE Connection Program: Psychopharmacological Treatment of People With a First Episode of Schizophrenia. AB - OBJECTIVE: This study examined the adherence of psychiatrists to the Schedule of Recommended First and Second Line Antipsychotic Medications ("Antipsychotic Schedule"), which was implemented in two Recovery After an Initial Schizophrenia Episode (RAISE) Connection Program Implementation and Evaluation Study clinics. METHODS: Sixty-five individuals with a first episode of psychosis were enrolled in the RAISE Connection Program clinics. Two psychiatrists received training and ongoing consultation on use of a shared decision-making approach to prescribing antipsychotic medications according to the Antipsychotic Schedule. Information about participants, prescribed antipsychotic medications, and completion of side effect assessments were obtained from standardized research assessments and chart extractions. Descriptive statistics were used to characterize the extent to which patterns of antipsychotic prescribing and side-effect monitoring were consistent with the Antipsychotic Schedule. RESULTS: Ninety-two percent of participants were prescribed an antipsychotic medication and received the medication on 76%+/-35% of the days they were in treatment. Seventy-seven percent of participants were prescribed at least one Antipsychotic Schedule first-line antipsychotic, 20% were prescribed olanzapine, and 10% received a trial of clozapine. Regarding monitoring for metabolic side effects, 92% of participants had at least one weight recorded, 72% had at least one blood glucose measure recorded, and 62% had at least one lipid profile recorded. CONCLUSIONS: In the context of a study in which training and ongoing clinical supervision by experts was provided to psychiatrists and shared decision making was encouraged, antipsychotic prescribing patterns closely adhered to recommendations established by the RAISE Connection Program. PMID- 27364817 TI - Uses of Research Evidence by State Legislators Who Prioritize Behavioral Health Issues. AB - OBJECTIVE: Disseminating behavioral health (BH) research to elected policy makers is a priority, but little is known about how they use and seek research evidence. This exploratory study aimed to identify research dissemination preferences and research-seeking practices of legislators who prioritize BH issues and to describe the role of research in determining policy priorities. The study also assessed whether these legislators differ from those who do not prioritize BH issues. METHODS: A telephone-based survey was conducted with 862 state legislators (response rate, 46%). A validated survey instrument assessed priorities and the factors that determined them, research dissemination preferences, and research-seeking practices. Bivariate analyses were used to characterize and compare the two groups. RESULTS: Legislators who prioritized BH issues (N=125) were significantly more likely than those who did not to identify research evidence as a factor that determined policy priorities (odds ratio=1.91, 95% confidence interval=1.25-2.90, p=.002). Those who prioritized BH issues also attributed more importance to ten of 12 features of research, and the difference was significant for four features (unbiased, p=.014; presented in a concise way, p=.044; delivered by someone known or respected, p=.033; and tells a story, p=.030). Those who prioritized BH issues also engaged more often in eight of 11 research-seeking and utilization practices, and a significance difference was found for one (attending research presentations, p=.012). CONCLUSIONS: Legislators who prioritized BH issues actively sought, had distinct preferences for, and were particularly influenced by research evidence. Testing legislator focused BH research dissemination strategies is an area for future research. PMID- 27364818 TI - [Dermatological diseases of the external male genitalia : Part 2: Infectious and malignant dermatological]. AB - The urological and andrological examination of male patients should include inspection of the genital skin in order to detect malignant neoplasms, such as erythroplasia of Queyrat and infectious diseases, such as genital warts (condylomata acuminata). Independent of the incidental finding of relevant dermatological alterations in the genital area, sexually transmitted diseases such as syphilis must again be considered more often as the incidence has greatly increased in Germany during the last few years. In addition, urologists should be able to adequately advise patients on all aspects of diseases caused by human papillomavirus. As patients are often alarmed by genital skin lesions and worried that the sex life can be impaired, the initiation of adequate therapy is of great importance. PMID- 27364819 TI - [What do prostate cancer patients know about smoking? : Results of a bicentric questionnaire study (KRAUT study)]. AB - BACKGROUND: According to the results of a recent meta-analysis, cancer-specific mortality of prostate cancer (PCA) patients is enhanced by 24 % in case of a positive smoking history with a dose-dependent impact of smoking. Until now it is unknown whether this information actually reaches the patients and how extensively an informational discussion about this topic is pursued by physicians. OBJECTIVE: Three study hypotheses were defined: (1) the knowledge of PCA patients about the potential relationship between tumor progression and cigarette consumption is low, (2) only in rare cases has a clear statement been provided by treating physicians including the explicit advice to stop smoking, and (3) there was a direct association between tumor stage and the extent of cigarette consumption. MATERIALS AND METHODS: A questionnaire comprising 23 items was developed and validated with 25 uro-oncological patients prior to study start. Between September 2013 and December 2014 a total of 124 PCA patients (median age 65 years) from two urology departments were included in this questionnaire-based survey. RESULTS: The study population comprised 43 % (n = 54), 39 % (n = 48), and 18 % (n = 22) nonsmokers, former smokers and active smokers, respectively. Active and former smokers differed insignificantly in the number of pack-years only (24.8 vs. 23.7 years, p = 0.995). Of the patients, 56 % regarded an influence of cigarette consumption on the PCA-specific prognosis as possible. However, because a significant (p < 0.001) number of patients wrongly suspected smoking to be causative for PCA development, their knowledge about PCA prognosis is supposedly not based on adequate knowledge. Two of 22 active smokers (9.1 %), 5 of 48 former smokers (10.4 %), and 2 of 54 nonsmokers (3.7 %) had an informational discussion with their urologist about the association of cigarette consumption and PCA-related prognosis (a further 9.1, 4.2 and 3.7 %, respectively, received this information solely from other medical specialties). Only 1 of 22 active smokers (4.5 %) was offered medical aids for smoking cessation by the general practitioner; none of the patients received such support by an urologist. There was no association between a positive smoking history or number of pack-years and PCA tumor stage. CONCLUSIONS: Education of PCA patients about the relationship between cigarette consumption and cancer-related prognosis is currently inadequate. Following the latest findings on this topic, urologists should pursue informational discussions with their patients, thereby strengthening their position as the primary contact person for decision making in PCA management. PMID- 27364820 TI - [Is urolithiasis a contradiction for vitamin D and calcium supplementation?] PMID- 27364821 TI - [Causes of hospital readmission after urologic cancer surgery]. PMID- 27364822 TI - Caffey's Disease: Two Cases Presenting with Unexplained Fever. PMID- 27364824 TI - Intestinal Necrosis with Midgut Malrotation and Intermittent Volvulus: Presentation as Acute Abdominal Pain in an Adult. PMID- 27364823 TI - The Severity of Bleeding and Mortality in Trauma Patients Taking Dabigatran. AB - BACKGROUND: Dabigatran, a direct thrombin inhibitor, has been shown to be more effective than warfarin in the prevention of stroke in patients with atrial fibrillation. Until recently, it lacked a reversal agent, and its contribution to the risk of transfusion in injured patients is unknown. OBJECTIVE: We sought to determine whether patients who sustain traumatic injuries while taking dabigatran receive more blood transfusions than matched patients taking warfarin, aspirin, clopidogrel, or controls. METHODS: This retrospective, single-center cohort consisted of injured patients who were taking dabigatran before admission to a major trauma center (January 2010-December 2013) who were compared with cohorts of patients taking warfarin, clopidogrel, or aspirin and a control group. The outcome was bleeding risk as measured by the use of blood products, with mortality as a secondary outcome. Outcomes were controlled for by age, sex, injury severity, and blunt mechanism. RESULTS: Thirty-eight patients were taking dabigatran. Compared with the general trauma population, patients taking dabigatran were more likely to be male, older, and to have higher injury severity. Patients taking dabigatran received transfusions (odds ratio [OR] 1.31 [95% confidence interval {CI} 0.56-3.04]), packed red blood cells (OR 1.43 [95% CI 0.54-3.77]), frozen plasma (OR 1.20 [95% CI 0.42-3.49]), and platelets (OR 2.01 [95% CI 0.63-6.37]) as often as matched controls. The mortality rate among patients on dabigatran was 12.5% (OR 1.51 [95% CI 0.39-5.89]) compared with 9.1% in matched controls. None of these results was statistically significant. CONCLUSIONS: In this small study, injured patients taking dabigatran were transfused as often and had similar in-hospital mortality as matched controls who were not taking anticoagulants. PMID- 27364825 TI - Extreme Hyperpyrexia of Uncertain Origin. AB - BACKGROUND: The definition of hyperpyrexia is currently limited to temperatures reaching 106.7 degrees F. A wide range of etiologies have been identified in the literature for an insidious onset of hyperpryexia, however a rapid ascent higher than temperatures of 106.7 degrees F has never been reported nor evaluated. We present the case of a young paraplegic who developed an extreme hyperpyrexia, which to our knowledge is the highest occurring temperature reported in contemporary medical literature. He had a number of medical conditions, none of which are known to produce fever. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Fever, although a common presentation in the ER in the presence of various symptoms and comorbidities can obscure the diagnosis and lead to unwarranted evaluations. As such this patients case identifies a diagnosis of a fatal ascension of fever. PMID- 27364827 TI - The effect of linoleic acid on the Sauvignon blanc fermentation by different wine yeast strains. AB - The level of linoleic acid in the Sauvignon blanc (SB) grape juice affects the development of different aroma compounds during fermentation by Saccharomyces cerevisiae EC1118, including key varietal thiols such as 3-mercaptohexanol (3MH) and 3-mercaptohexyl acetate (3MHA). However, it is still unknown if linoleic acid would affect in a similar way other commonly used S. cerevisiae wine strains. Here we investigated the effect of grape juice linoleic acid on the development of aroma compounds and other metabolites of SB wines using different wine yeast strains: EC1118, AWRI796 and VIN13. Linoleic acid clearly affected the levels of acetylated aroma compounds, several amino acids, and antioxidant molecules, independent of yeast strain, but the production of 3MH was affected by linoleic acid in a strain-specific manner. Moreover, the supplementation of deuterium labelled 3MH also affected the production of varietal thiols in a strain-specific way. Linoleic acid reduced the acetylation process probably by inhibiting an acetyltransferase, an effect that was independent of the yeast strain. However, regulation of the 3MH biosynthesis is strain-specific, which suggests a mindful consideration not only towards the wine yeast but also to the linoleic acid concentration in the grape juice in order to obtain the desired wine aroma characteristics. PMID- 27364826 TI - Maltose and maltotriose utilisation by group I strains of the hybrid lager yeast Saccharomyces pastorianus. AB - Brewer's wort is a challenging environment for yeast as it contains predominantly alpha-glucoside sugars. There exist two subgroups of the lager yeast Saccharomyces pastorianus which differ in sugar utilisation. We performed wort fermentations and compared representative strains from both groups with respect to their ability to transport and ferment maltose and maltotriose. Additionally, we mapped the transporters MALx1, AGT1, MPHx and MTT1 by Southern blotting. Contrary to previous observations, group I comprises a diverse set of strains, with varying ability to transport and ferment maltotriose. Of the eight group I strains, three efficiently utilised maltotriose, a property enabled by the presence of transmembrane transporters SeAGT1 and MTT1 A58, a variant of the group I type strain (CBS1513) performed particularly well, taking up maltotriose at a higher rate than maltose and retaining significant transport activity at temperatures as low as 0 degrees C. Analysis of transporter distribution in this strain revealed an increased copy number of the MTT1 gene, which encodes the only permease known with higher affinity for maltotriose than maltose and low temperature dependence for transport. We propose that much of the variation in lager yeast fermentation behaviour is determined by the presence or absence of specific transmembrane transporters. PMID- 27364829 TI - Factors Affecting the Pharmacokinetics, Biodistribution and Toxicity of Gold Nanoparticles in Drug Delivery. AB - Owing to the straightforward synthesis, good biological compatibility, and ease of surface functionalization, gold nanoparticles (AuNPs) have shown great potential in various biomedical applications, including diagnostic imaging, photothermal therapy (PTT), and drug delivery. Physicochemical properties (e.g. shape, size and surface chemistry) may potentially affect the interaction of AuNPs with biological systems, thus ultimately influencing their cell uptake, pharmacokinetics, biodistribution, drug delivery efficiency, and biological effects. This review focuses on recent advances in understanding the relation between physicochemical characteristics of AuNPs and their navigation through different biological processes, including biodistribution, penetration of biological barriers (e.g. blood-brain barrier), clearance, and metabolism. Furthermore, the in vitro and in vivo toxicological effects of AuNPs and their possible mechanisms were discussed. A thorough understanding of these influencing factors will be crucial for the rational design, customized functionalization, and clinical translation of AuNPs in drug delivery. PMID- 27364830 TI - The Role of Drug Transporters in the Pharmacokinetics of Antibiotics. AB - BACKGROUND: Various transporters, including efflux transporters and uptake transporters, play an important role in the pharmacokinetics of drugs. Currently, studies suggest that several antibiotics also serve as substrates for transporters. In addition, these antibiotics are usually combined with other drugs to treat diseases, more effectively. Therefore, it is necessary to focus on the role of transporters in pharmacokinetics and drug-drug interactions of antibiotics. METHODS: This review summarizes the findings of recent studies as well as information retrieved from several databases (until June 2015): ISI Web of KnowledgeSM (ISI WoK), SciFinder (Caplus, Medline, Registry, Casreact, Chrmlist, and Chemcasts) and PubMed (indexed for Medline). RESULTS: The present review provides useful information for the study of transporters in the pharmacokinetics and drug-drug interactions of antibiotics, and should assist researchers investigating these topics. CONCLUSION: The drug transporters mediate intestinal absorption, hepatic uptake, and kidney or biliary excretion. It is necessary to focus on drug-drug interactions when these antibiotics are combined with other chemical substances that are also the substrates for transporters. PMID- 27364831 TI - Salusins in Hypertension and Related Cardiovascular Diseases. AB - The salusins are bioactive peptides with hemodynamic effects. They play a role in hypertension, atherogenesis and cardiovascular diseases. In this review we focus on new actions, which are related to the regulation of blood pressure. Decrease in salusin- and the increase in salusin- concentrations are known to contribute to the development of the metabolic syndrome and atherosclerosis. Microinjections of salusin-. in the paraventricular nucleus (PVN) increases the plasma argininevasopressin (AVP) and norepinephrine levels, which contribute to hypertension. It also increases the AVP release from the rostral ventrolateral medulla (RVLM) via the projection from PVN to RVLM. Increased activity of the RVLM neurons is transmitted to the intermediolateral nucleus (IML) cell column of the spinal cord, where peripheral sympathetic nerves to the heart, arterioles and kidneys are activated, thus increasing blood pressure. Microinjection of salusin- into the RVLM increased renal sympathetic nerve activity, median arterial pressure (MAP) and heart rate (HR). There was no significant effect on the AVP level in the RVLM and plasma. Microinjection of salusin-. in the nucleus tractus solitarii (NTS) produces a dose dependent hypotension and bradycardia. Intravenous injection of salusin-. significant increased MAP, but did not have a meaningful outcome on HR. Nevertheless, intravenous injection of a very high dose of salusin-. caused instantaneous decrease in both MAP and HR. Salusin-. overexpression provoked severe and prolonged hypertension accompanied by tachycardia in rats. It is clear that more research needs to be done to evaluate the function of salusin- in the mechanism of essential hypertension, atherosclerosis, and the metabolic syndrome. PMID- 27364832 TI - P-gp Inhibition-Based Strategies for Modulating Pharmacokinetics of Anticancer Drugs: An Update. AB - BACKGROUND: P-glycoprotein (P-gp), a well known ATP dependent efflux membrane transporter, has been attracting considerable interests of medical researchers due to its efflux pump effect being a primary cause of multidrug resistance (MDR) and poor bioavailability (BA) of anticancer agents. How to resolve the aforesaid problems has become the research hot-points in the medical and pharmaceutical fields. The past three decades have witnessed rapid development of the P-gp inhibition-based strategies used for modulating pharmacokinetics (PK) and thus overcoming MDR and improving BA of anticancer drugs. METHODS: An electronic search of PubMed database from inception to April, 2016 was conducted. Additionally, we searched the reference lists of included studies and carried out a citation search for the included studies via Web of Science to find other potentially relevant studies. RESULTS AND CONCLUSION: Lots of the studies of the P-gp inhibition-based strategies are under preclinical phase and the obtained results are exciting and may represent great promise in the clinical application potential. In order to provide useful information for the development of novel strategies for improving BA of anticancer drugs, this article aims to review the research progress in the P-gp inhibition-based strategies that has been acquired over the last three decades, with focus on the P-gp inhibitors, herbal constituents and pharmaceutical excipients as well as novel P-gp-linked drug delivery systems (DDSs). Additionally, the fundamental knowledge on P-gp also is briefly discussed. PMID- 27364833 TI - Uncoupling protein 2 protects mice from aging. AB - Uncoupling protein (UCP) 2 is a mitochondrial transporter protein that plays various roles in cellular metabolism, including the glucose and lipid metabolism. Polymorphisms in UCP2 are associated with longevity in humans. In line with this, mice carrying the UCP2 transgene under the control of hypocretin promoter were reported to have an extended lifespan, while, conversely, mice deficient in Ucp2 demonstrated a significantly shorter lifespan. In this study, we examined the phenotype of aging in a large colony of Ucp2-deficient (Ucp2(-/-)) mice on the molecular level. We have found that the significantly shorter lives of Ucp2(-/-) mice is the result of an accelerated aging process throughout their entire lifespan. Thus, Ucp2(-/-) mice not only earlier gained sexual maturity, but also earlier progressed into an aging phenotype, reflected by a decrease in body weight, increased neutrophil numbers, and earlier emergence of spontaneous ulcerative dermatitis. Intriguingly, on the molecular level this acceleration in aging predominantly driven by increased levels of circulating IGF-1 in Ucp2(-/-) mice, hinting at a crosstalk between UCP2 and the classical Insulin/IGF-1 signaling aging pathway. PMID- 27364849 TI - Erratum for Salipante et al., Performance Comparison of Illumina and Ion Torrent Next-Generation Sequencing Platforms for 16S rRNA-Based Bacterial Community Profiling. PMID- 27364834 TI - Receipt of Cancer Screening Is a Predictor of Life Expectancy. AB - BACKGROUND: Obtaining cancer screening on patients with limited life expectancy has been proposed as a measure for low quality care for primary care physicians (PCPs). However, administrative data may underestimate life expectancy in patients who undergo screening. OBJECTIVE: To determine the association between receipt of screening mammography or PSA and overall survival. DESIGN: Retrospective cohort study from 1/1/1999 to 12/31/2012. Receipt of screening was assessed for 2001-2002 and survival from 1/1/2003 to 12/31/2012. Life expectancy was estimated as of 1/1/03 using a validated algorithm, and was compared to actual survival for men and women, stratified by receipt of cancer screening. PARTICIPANTS: A 5 % sample of Medicare beneficiaries aged 69-90 years as of 1/1/2003 (n = 906,723). INTERVENTIONS: Receipt of screening mammography in 2001 2002 for women, or a screening PSA test in 2002 for men. MAIN MEASURES: Survival from 1/1/2003 through 12/31/2012. KEY RESULTS: Subjects were stratified by life expectancy based on age and comorbidity. Within each stratum, the subjects with prior cancer screening had actual median survivals higher than those who were not screened, with differences ranging from 1.7 to 2.1 years for women and 0.9 to 1.1 years for men. In a Cox model, non-receipt of screening in women had an impact on survival (HR = 1.52; 95 % CI = 1.51, 1.54) similar in magnitude to a diagnosis of complicated diabetes or heart failure, and was comparable to uncomplicated diabetes or liver disease in men (HR = 1.23; 1.22, 1.25). CONCLUSIONS: Receipt of cancer screening is a powerful marker of health status that is not captured by comorbidity measures in administrative data. Because life expectancy algorithms using administrative data underestimate the life expectancy of patients who undergo screening, they can overestimate the problem of cancer screening in patients with limited life expectancy. PMID- 27364851 TI - Technological aids for the rehabilitation of memory and executive functioning in children and adolescents with acquired brain injury. AB - BACKGROUND: The use of technology in healthcare settings is on the increase and may represent a cost-effective means of delivering rehabilitation. Reductions in treatment time, and delivery in the home, are also thought to be benefits of this approach. Children and adolescents with brain injury often experience deficits in memory and executive functioning that can negatively affect their school work, social lives, and future occupations. Effective interventions that can be delivered at home, without the need for high-cost clinical involvement, could provide a means to address a current lack of provision.We have systematically reviewed studies examining the effects of technology-based interventions for the rehabilitation of deficits in memory and executive functioning in children and adolescents with acquired brain injury. OBJECTIVES: To assess the effects of technology-based interventions compared to placebo intervention, no treatment, or other types of intervention, on the executive functioning and memory of children and adolescents with acquired brain injury. SEARCH METHODS: We ran the search on the 30 September 2015. We searched the Cochrane Injuries Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), EMBASE Classic + EMBASE (OvidSP), ISI Web of Science (SCI-EXPANDED, SSCI, CPCI-S, and CPSI-SSH), CINAHL Plus (EBSCO), two other databases, and clinical trials registers. We also searched the internet, screened reference lists, and contacted authors of included studies. SELECTION CRITERIA: Randomised controlled trials comparing the use of a technological aid for the rehabilitation of children and adolescents with memory or executive-functioning deficits with placebo, no treatment, or another intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed titles and abstracts identified by the search strategy. Following retrieval of full-text manuscripts, two review authors independently performed data extraction and assessed the risk of bias. MAIN RESULTS: Four studies (involving 206 participants) met the inclusion criteria for this review.Three studies, involving 194 participants, assessed the effects of online interventions to target executive functioning (that is monitoring and changing behaviour, problem solving, planning, etc.). These studies, which were all conducted by the same research team, compared online interventions against a 'placebo' (participants were given internet resources on brain injury). The interventions were delivered in the family home with additional support or training, or both, from a psychologist or doctoral student. The fourth study investigated the use of a computer program to target memory in addition to components of executive functioning (that is attention, organisation, and problem solving). No information on the study setting was provided, however a speech-language pathologist, teacher, or occupational therapist accompanied participants.Two studies assessed adolescents and young adults with mild to severe traumatic brain injury (TBI), while the remaining two studies assessed children and adolescents with moderate to severe TBI. Risk of biasWe assessed the risk of selection bias as low for three studies and unclear for one study. Allocation bias was high in two studies, unclear in one study, and low in one study. Only one study (n = 120) was able to conceal allocation from participants, therefore overall selection bias was assessed as high.One study took steps to conceal assessors from allocation (low risk of detection bias), while the other three did not do so (high risk of detection bias). Primary outcome 1: Executive functioning: Technology-based intervention versus placeboResults from meta-analysis of three studies (n = 194) comparing online interventions with a placebo for children and adolescents with TBI, favoured the intervention immediately post-treatment (standardised mean difference (SMD) -0.37, 95% confidence interval (CI) -0.66 to 0.09; P = 0.62; I(2) = 0%). (As there is no 'gold standard' measure in the field, we have not translated the SMD back to any particular scale.) This result is thought to represent only a small to medium effect size (using Cohen's rule of thumb, where 0.2 is a small effect, 0.5 a medium one, and 0.8 or above is a large effect); this is unlikely to have a clinically important effect on the participant.The fourth study (n = 12) reported differences between the intervention and control groups on problem solving (an important component of executive functioning). No means or standard deviations were presented for this outcome, therefore an effect size could not be calculated.The quality of evidence for this outcome according to GRADE was very low. This means future research is highly likely to change the estimate of effect. Primary outcome 2: MemoryOne small study (n = 12) reported a statistically significant difference in improvement in sentence recall between the intervention and control group following an eight-week remediation programme. No means or standard deviations were presented for this outcome, therefore an effect size could not be calculated. Secondary outcomesTwo studies (n = 158) reported on anxiety/depression as measured by the Child Behavior Checklist (CBCL) and were included in a meta-analysis. We found no evidence of an effect with the intervention (mean difference -5.59, 95% CI -11.46 to 0.28; I(2) = 53%). The GRADE quality of evidence for this outcome was very low, meaning future research is likely to change the estimate of effect.A single study sought to record adverse events and reported none. Two studies reported on use of the intervention (range 0 to 13 and 1 to 24 sessions). One study reported on social functioning/social competence and found no effect. The included studies reported no data for other secondary outcomes (that is quality of life and academic achievement). AUTHORS' CONCLUSIONS: This review provides low-quality evidence for the use of technology-based interventions in the rehabilitation of executive functions and memory for children and adolescents with TBI. As all of the included studies contained relatively small numbers of participants (12 to 120), our findings should be interpreted with caution. The involvement of a clinician or therapist, rather than use of the technology, may have led to the success of these interventions. Future research should seek to replicate these findings with larger samples, in other regions, using ecologically valid outcome measures, and reduced clinician involvement. PMID- 27364853 TI - Decarboxylative Anti-Michael Addition to Olefins Mediated by Photoredox Catalysis. AB - Decarboxylative coupling of carboxylic acids with activated olefins has been accomplished using visible light photoredox catalysis. The strategic placement of a radical-stabilizing aromatic group at the beta-position of the olefin component biases the regioselectivity of the addition, allowing reliable, facile access to anti-Michael-type products from readily available precursors. The scope of this methodology was demonstrated with a range of carboxylic acids and appropriately substituted olefins and was applied toward a two-step synthesis of the antiarrhythmic agent encainide. PMID- 27364852 TI - High post-movement parietal low-beta power during rhythmic tapping facilitates performance in a stop task. AB - Voluntary movements are followed by a post-movement electroencephalography (EEG) beta rebound, which increases with practice and confidence in a task. We hypothesized that greater beta modulation reflects less load on cognitive resources and may thus be associated with faster reactions to new stimuli. EEG was recorded in 17 healthy subjects during rhythmically paced index finger tapping. In a STOP condition, participants had to interrupt the upcoming tap in response to an auditory cue, which was timed such that stopping was successful only in ~ 50% of all trials. In a second condition, participants carried on tapping twice after the stop signal (CONTINUE condition). Thus the conditions were distinct in whether abrupt stopping was required as a second task. Modulation of 12-20 Hz power over motor and parietal areas developed with time on each trial and more so in the CONTINUE condition. Reduced modulation in the STOP condition went along with reduced negative mean asynchronies suggesting less confident anticipation of the timing of the next tap. Yet participants were more likely to stop when beta modulation prior to the stop cue was more pronounced. In the STOP condition, expectancy of the stop signal may have increased cognitive load during movement execution given that the task might have to be stopped abruptly. However, within this condition, stopping ability was increased if the preceding tap was followed by a relatively larger beta increase. Significant, albeit weak, correlations confirmed that increased post-movement beta power was associated with faster reactions to new stimuli, consistent with reduced cognitive load. PMID- 27364854 TI - Sex Difference in the Association Between Brachial Pulse Pressure and Coronary Artery Disease: The Korean Women's Chest Pain Registry (KoROSE). AB - This study was performed to investigate the association between brachial pulse pressure (PP) and the presence/extent of obstructive coronary artery disease (CAD) in men and women. Study data were obtained from a nation-wide registry composed of 632 patients (173 men and 459 women, 58.1+/-10.5 years) with suspected CAD who underwent invasive coronary angiography. PP was higher in patients with obstructive CAD (>=50% stenosis) than those without CAD in both sexes (P=.032 in men; P<.001 in women). However, PP increased proportionally with the increasing number of obstructed coronary arteries in women (P<.001) but not in men (P=.070). Multiple logistic-regression analyses demonstrated that higher PP (>=50.5 mm Hg) was an independent factor for determining obstructive CAD even after controlling for potential confounders in women (odds ratio, 2.83; 95% confidence interval, 1.40-5.73; P=.004). These results were consistent in 173 selected women matched with 173 men based on age and CAD severity. In conclusion, the association between brachial PP and obstructive CAD was more pronounced in women than in men. Brachial PP can be a simple and useful indicator of CAD especially in women. PMID- 27364855 TI - Stimulatory effect of CSE-generated H2S on hepatic mitochondrial biogenesis and the underlying mechanisms. AB - We previously showed that hydrogen sulfide (H2S) upregulates peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha in primary hepatocytes. PGC-1alpha is a crucial regulator of mitochondrial biogenesis, a process required to maintain cellular energy homeostasis. We investigated the regulation of hepatic mitochondrial biogenesis by cystathionine gamma-lyase (CSE) generated H2S under physiological conditions. Primary hepatocytes isolated from CSE knockout (KO) and wild-type (WT) mice were used in all experiments. Mitochondrial DNA (mtDNA) and mRNA levels were measured via real-time PCR. Protein S-sulfhydration was determined via a modified biotin switch assay. MitoTracker Green was used to quantify mitochondrial content and distribution. CSE-KO hepatocytes produced less mtDNA compared to WT hepatocytes. Mitochondrial content was reduced in CSE-KO hepatocytes compared to WT hepatocytes, which was restored with NaHS (an H2S donor) treatment. CSE-KO hepatocytes exhibited lower levels of mitochondrial transcription factors and the mitochondrial transcription coactivator, peroxisome proliferator-activated receptor-gamma coactivator-related protein (PPRC) compared to WT hepatocytes. NaHS administration upregulated PPRC, yet downregulated PGC-1beta protein level in mouse hepatocytes. Exogenous H2S induced the S-sulfhydration of PPRC, which was lower in untreated CSE-KO hepatocytes, but not that of PGC-1beta. Finally, knockdown of either PGC-1alpha or PPRC significantly decreased NaHS-stimulated mitochondrial biogenesis in hepatocytes, where knockdown of both genes were required to abolish NaHS-induced mitochondrial biogenesis. Endogenous H2S-induced liver mitochondrial biogenesis is dependent upon PGC-1alpha and PPRC signaling in primary hepatocytes. This study may offer clues to the regulation of energy homeostasis under physiological conditions as well as mitochondrial dysregulation. PMID- 27364856 TI - Integration scheme of nanoscale resistive switching memory using bottom-up processes at room temperature for high-density memory applications. AB - A facile and versatile scheme is demonstrated to fabricate nanoscale resistive switching memory devices that exhibit reliable bipolar switching behavior. A solution process is used to synthesize the copper oxide layer into 250-nm via holes that had been patterned in Si wafers. Direct bottom-up filling of copper oxide can facilitate fabrication of nanoscale memory devices without using vacuum deposition and etching processes. In addition, all materials and processes are CMOS compatible, and especially, the devices can be fabricated at room temperature. Nanoscale memory devices synthesized on wafers having 250-nm via holes showed reproducible resistive switching programmable memory characteristics with reasonable endurance and data retention properties. This integration strategy provides a solution to overcome the scaling limit of current memory device fabrication methods. PMID- 27364857 TI - Editor's Choice - Delays to Surgery and Procedural Risks Following Carotid Endarterectomy in the UK National Vascular Registry. AB - OBJECTIVE: Guidelines recommend that patients suffering an ischaemic transient ischaemic attack (TIA) or stroke caused by carotid artery stenosis should undergo carotid endarterectomy (CEA) within 14 days. METHOD: The degree to which UK vascular units met this standard was examined and whether rapid interventions were associated with procedural risks. The study analysed patients undergoing CEA between January 2009 and December 2014 from 100 UK NHS hospitals. Data were collected on patient characteristics, intervals of time from symptoms to surgery, and 30-day postoperative outcomes. The relationship between outcomes and time from symptom to surgery was evaluated using multilevel multivariable logistic regression. RESULTS: In 23,235 patients, the median time from TIA/stroke to CEA decreased over time, from 22 days (IQR 10-56) in 2009 to 12 days (IQR 7-26) in 2014. The proportion of patients treated within 14 days increased from 37% to 58%. This improvement was produced by shorter times across the care pathway: symptoms to referral, from medical review to being seen by a vascular surgeon, and then to surgery. The spread of the median time from symptom to surgery among NHS hospitals shrank between 2009 and 2013 but then grew slightly. Low-, medium-, and high-volume NHS hospitals all improved their performance similarly. Performing CEA within 48 h of symptom onset was associated with a small increase in the 30-day stroke and death rate: 3.1% (0-2 days) compared with 2.0% (3-7 days); adjusted odds ratio 1.64 (95% CI 1.04-2.59) but not with longer delays. CONCLUSIONS: The delay from symptom to CEA in symptomatic patients with ipsilateral 50-99% carotid stenoses has reduced substantially, although 42% of patients underwent CEA after the recommended 14 days. The risk of stroke after CEA was low, but there may be a small increase in risk during the first 48 h after symptoms. PMID- 27364858 TI - The impact of Bakri balloon tamponade on the rate of postpartum hysterectomy for uterine atony. AB - OBJECTIVE: Our objective was to evaluate the impact of uterine tamponade with a Bakri balloon on the rate of postpartum hysterectomy due to uterine atony. METHODS: We performed a retrospective cohort study of all deliveries >20 weeks gestation from January 2002 to March 2013 at Baystate Medical Center. Charts were reviewed to determine incidence of postpartum hysterectomy, Bakri balloon placement, uterine artery embolization (UAE) and the B-Lynch procedure. Patients with evidence of placenta accreta were excluded. The primary outcome was the change in rates of postpartum hysterectomy for uterine atony before and after the introduction of Bakri balloon tamponade, using chi-square testing. RESULTS: There were 48 767 deliveries during the study period, with 17 950 before and 30 817 after the introduction of the Bakri balloon. A total of 43 Bakri balloons were placed during the study period and 21 hysterectomies were performed for postpartum hemorrhage secondary to uterine atony, 14 before and 7 after the introduction of the Bakri balloon. This was consistent with a decrease in the rate of postpartum hysterectomy from 7.8/10 000 deliveries to 2.3/10 000 deliveries (p = 0.01). CONCLUSION: Our findings show that utilization of the Bakri balloon is associated with a decreased rate of postpartum hysterectomy. PMID- 27364859 TI - Factors Determining Bone Mineral Density in Patients with Biliary Atresia after a Successful Kasai Operation. AB - BACKGROUND: Hepatic osteodystrophy is a common complication in patients with chronic liver disease, however, bone mineral status in patients with biliary atresia has rarely been investigated. METHODS: Twenty-nine children with biliary atresia were enrolled in our study and their demographic data, bone mineral density (BMD) of lumbar spine and bilateral femoral neck, and biochemical parameters were measured and analyzed. RESULTS: The majority of our patients had osteopenia or osteoporosis over at least one part of the skeleton although none had jaundice. Instead of T helper 1 cell cytokine, interleukin (IL)-4 had a significant negative correlation with BMD of the right femoral neck (beta = 0.251, p = 0.027) and left femoral neck (beta = -0.299, p = 0.012) independently by multiple linear regression analysis. CONCLUSION: We conclude that chronic inflammation with increased expression of IL-4 may be an important factor for compromised bone health in patients with biliary atresia. PMID- 27364860 TI - Rebound Thymic Hyperplasia after Chemotherapy in Children with Lymphoma. AB - BACKGROUND: Development of mediastinal masses after completion of chemotherapy in pediatric patients with malignant lymphoma is worrisome and challenging to clinicians. METHODS: We performed a retrospective review of 67 patients with lymphoma treated at our hospital from January 1, 2001 to June 1, 2013. Patients who received at least two chest computed tomography (CT) examinations after complete remission (CR) was achieved were further analyzed. Gallium-67 scans and positron emission tomography (PET) were recorded and compared between these patients. RESULTS: Sixty-two of 67 patients reached CR, of whom 31 (22 male, 9 female) were patients that received at least two chest CT examinations after CR. Rebound thymic hyperplasia (RTH) was diagnosed in 21/31 patients (67.7%), including 14/23 (60.9%) and seven out of eight (87.5%) with non-Hodgkin's lymphoma and Hodgkin's lymphoma, respectively. Ages ranged from 3 years to 18 years (median 10 years). Increased radioactivity uptake of the anterior mediastinum in gallium scans was found in nine out of 20 patients (45%) with thymic rebound. PET was performed in six out of 21 patients. Increased fluorodeoxyglucose (FDG)-avid uptake in the anterior mediastinum was observed in four of six patients (66.7%) by PET. One patient received thymectomy. No patients with RTH had lymphoma relapse within the median follow-up period (5 years). Relapse was statistically significantly different (p = 0.001) between patients with and without RTH. CONCLUSION: RTH developed in 67.7% of pediatric patients with lymphoma in CR after chemotherapy. The association of RTH development and lowered relapse rates has yet to be determined. Awareness of this phenomenon is important in the prevention of unnecessary surgical intervention or chemotherapy. PMID- 27364861 TI - Risk Factors and Management of Urinary Tract Infections in Children Aged 3 Months to 2 Years. PMID- 27364862 TI - Source function and plane waves: Toward complete bader analysis. AB - The source function (SF) is a topological descriptor that was introduced and developed by C. Gatti and R.W. Bader in 1998. The SF describes the contribution of each atom to the total electron density at a given point. To date, this descriptor has only been calculable from electron densities generated by all electron (AE) methods for the investigation of single molecules or periodic systems. This study broadens the accessibility of the SF, offering its calculation from electron densities generated by plane wave (PW) methods. The new algorithm has been implemented in the open source code, CRITIC2. Our novel approach has been validated on a series of test systems, comparing the results obtained at PW level with those previously obtained through AE methods. (c) 2016 Wiley Periodicals, Inc. PMID- 27364863 TI - Optimal numbers of residues in linkers of DNA polymerase I, T7 primase and DNA polymerase IV. AB - DNA polymerase I (PolI), T7 primase and DNA polymerase IV (Dpo4) have a common feature in their structures that the two main domains are connected by an unstructured polypeptide linker. To perform their specific enzymatic activities, the enzymes are required to rearrange the position and orientation of one domain relative to the other into an active mode. Here, we show that the three enzymes share the same mechanism of the transition from the inert to active modes and use the minimum numbers of residues in their linkers to achieve the most efficient transitions. The transition time to the finally active mode is sensitively dependent on the stretched length of the linker in the finally active mode while is insensitive to the position and orientation in the initially inert state. Moreover, we find that for any enzyme whose two domains are connected by an unstructured flexible linker, the stretched length (L) of the linker in the finally active mode and the optimal number (Nopt) of the residues in the linker satisfy relation L ~ alphaNopt, with alpha = 0.24-0.27 nm being a constant insensitive to the system. PMID- 27364864 TI - Bioaccumulation and persistence of faecal bacterial and viral indicators in Mytilus edulis and Crassostrea gigas. AB - This study investigated the response of two shellfish species - mussels (Mytilus edulis) and oysters (Crassostrea gigas) to microbial contamination in order to gain a better understanding of the bioaccumulation and persistence of microorganisms under controlled conditions. M. edulis and C. gigas were placed in sterile laboratory-prepared artificial seawater and initial tests were carried out to ensure both faecal indicator bacteria (FIB) and bacteriophages were below detection limits. FIB and phages were isolated, purified and dosed into experimental tanks containing the shellfish species. The GB124 phages were bioaccumulated to the highest concentration in M. edulis (1.88Log10) and C. gigas (1.27Log10) after 24h. Somatic coliphages were bioaccumulated to the highest concentration in both M. edulis (4.84log10) and C. gigas (1.73log10) after 48h. F RNA phages were bioaccumulated to the highest concentration in M. edulis (3.51log10) after 6h but were below detection limit in C. gigas throughout the exposure period. Escherichia coli, faecal coliforms and intestinal enterococci were bioaccumulated to the highest concentrations in M. edulis (5.05log10, 5.06log10 and 3.98log10, respectively) after 48h. In C. gigas, E. coli reached a maximum concentration (5.47log10) after 6h, faecal coliforms (5.19log10) after 12h and intestinal enterococci (3.23log10) after 24h.M. edulis bioaccumulated phages to a greater extent than the faecal bacteria, and in both shellfish species, faecal bacteria persisted for longer periods over 48h than the phages. This study highlights significant variation in the levels and rate of accumulation and persistence with respect to both shellfish species and the indicators used to assess risk. The results suggest that phage-based indicators could help elucidate risks to human health associated with pathogenic organisms. PMID- 27364865 TI - Evaluation of Hyperbaric Oxygen Therapy in the Treatment of Radiation-induced Hemorrhagic Cystitis. PMID- 27364866 TI - Re: Romain et al.: Delayed-onset Ureteral Obstruction and Calcification Masquerading as Renal Colic Following Deflux Injection (Urology 2016;94:218-220). PMID- 27364867 TI - Urological Follow-up in Adult Spina Bifida Patients: Is There an Ideal Interval? AB - OBJECTIVE: To establish the time to development of urological issues over time in adult spina bifida (SB) patients. MATERIALS AND METHODS: This is a retrospective study of adult patients attending a multidisciplinary adult SB clinic from 2000 to 2013. Patient age, sex, number of clinic visits, and length of follow-up were recorded. For each unique visit, presence of symptoms, type of urological issue (if any), and time lapsed since last appointment were obtained. The interval between the development of urological issues was assessed using a time-to-event analysis. RESULTS: One hundred twenty-three patients (46% male, 54% female, median age 26.8years) were followed for a median of 48 months, contributing to 586 unique clinic visits. Urological issues were identified in 109 patients (88.5%) during 267 visits (46%), and of those 21% were asymptomatic. In symptomatic patients, the median time to present with a urological issue was 12 months. Among the asymptomatic cases, 12%, 23%, and 34% had developed a urological issue at 12, 24, and 36 months of follow-up, respectively. Eighty-one percent of the urological issues seen in the clinic required some form of treatment or intervention. The treatment or intervention in 56% of asymptomatic urological issues was surgery. CONCLUSION: Most adult SB patients with urological issues are symptomatic by 2 years of follow-up; however, over time the proportion of asymptomatic patients with urological issues rises steadily, reaching a worrisome 34% at 3 years. Closer follow-up seems warranted. PMID- 27364868 TI - Motor planning of goal-directed action is tuned by the emotional valence of the stimulus: a kinematic study. AB - The basic underpinnings of homeostatic behavior include interacting with positive items and avoiding negative ones. As the planning aspects of goal-directed actions can be inferred from their movement features, we investigated the kinematics of interacting with emotion-laden stimuli. Participants were instructed to grasp emotion-laden stimuli and bring them toward their bodies while the kinematics of their wrist movement was measured. The results showed that the time to peak velocity increased for bringing pleasant stimuli towards the body compared to unpleasant and neutral ones, suggesting higher easiness in undertaking the task with pleasant stimuli. Furthermore, bringing unpleasant stimuli towards the body increased movement time in comparison with both pleasant and neutral ones while the time to peak velocity for unpleasant stimuli was the same as for that of neutral stimuli. There was no change in the trajectory length among emotional categories. We conclude that during the "reach-to-grasp" and "bring-to-the-body" movements, the valence of the stimuli affects the temporal but not the spatial kinematic features of motion. To the best of our knowledge, we show for the first time that the kinematic features of a goal-directed action are tuned by the emotional valence of the stimuli. PMID- 27364869 TI - Family Caregiving in Japan: The Influence of Cultural Constructs in the Care of Adults With Cancer. AB - Caring culture is a concept embodying the perceptions and caring practices of caregivers, acknowledging the unique role of cultural beliefs in shaping behavior. A qualitative descriptive study with 13 caregivers of adult family members with a cancer diagnosis in Japan was conducted to gain insight into perceptions and experiences surrounding caregiving. Several major categories were identified, representing rarely reported cultural constructs of high cultural value for the Japanese: On-repayment for what the patient has given, Caregiving as performing a socially expected role, Enryo/meiwaku-restraint in asking for help, Family decision making reflecting strong bonds, Omoiyari-empathizing with the patient's feelings, and Inori-praying to myriad gods and ancestors. The Japanese cultural construct of ie (the strong relationship to family lineage and spiritual connection to past and future generations) is helpful in understanding these categories. Invisible yet powerful cultural constructs permeated caregiving practices. Insights from Japanese cultural concepts and beliefs may foster sensitivity and individualized care in diverse settings, cultures, and societies. PMID- 27364870 TI - A pilot study of intraluminal brachytherapy using 125I seed strand for locally advanced pancreatic ductal adenocarcinoma with obstructive jaundice. AB - PURPOSE: To investigate the safety and feasibility of intraluminal brachytherapy using 125I seed strand for locally advanced pancreatic ductal adenocarcinoma with obstructive jaundice. METHODS AND MATERIALS: From January 2010 to February 2015, 18 consecutive patients diagnosed with locally advanced, nonmetastatic, inoperable pancreatic ductal adenocarcinoma with obstructive jaundice were enrolled and underwent intraluminal brachytherapy using 125I seed strand. Dose calculation was performed using a software. The procedure-related and radiation complications were assessed. Obstruction-free survival and overall survival were calculated using the Kaplan-Meier method. RESULTS: The technique successful rate of 125I seed strand implantation was 100%. Successful bile drainage was achieved in all patients. The estimated mean accumulating dose (R = 5 mm, z = 0, 240 days) was 167.2 Gy, from 164.19 to 170.05 Gy. Two patients had adverse event of Grade 3, one of Grade 4. Stent dysfunction occurred in 1/18 (5.6%) patients. The mean and median obstruction-free survival time were 10.61 months (95% confidence interval [CI]: 7.04, 14.18) and 7.26 months (95% CI: 2.14, 12.38). The mean and median overall survival time were 11.91 months (95% CI: 7.39, 16.43) and 7.26 months (95% CI: 2.14, 12.38). CONCLUSIONS: Intraluminal brachytherapy using 125I seed strand may be consider as a safe treatment option for the therapy of locally advanced pancreatic duct adenocarcinoma complicated by obstructive jaundice with acceptable complication rates. PMID- 27364871 TI - Fractionated high-dose-rate brachytherapy as monotherapy in prostate cancer: Does implant displacement and its correction influence acute and late toxicity? AB - PURPOSE: In fractionated high-dose-rate brachytherapy (HDR-BT) for prostate cancer (PCa) with one implant for several fractions, dose delivery relies on reproducibility of catheter positions. However, caudal displacement of implanted catheters does occur between fractions and needs to be corrected. Our protocol prescribes correction of displacements > 3 mm. We investigated whether displacement and its corrections influence acute and late toxicity incidences. METHODS AND MATERIALS: We analyzed 162 PCa patients treated with HDR-BT monotherapy between 2007 and 2013. The implant remained in situ between the 4 fractions. Catheter displacement was assessed before each fraction using lateral X-ray images and corrected if needed. Genitourinary (GU) and gastrointestinal (GI) acute and late toxicities were assessed using clinical record forms and patient self-assessment questionnaires. RESULTS: Implant displacement corrections (DC) were needed in 71 patients (43.8%) whereas no DCs were needed in 91 patients (56.2%). No statistically significant differences were seen in acute and late grade >= 2 GU and GI toxicity incidences between DC and no DC groups. The maximum displacement nor the number of corrections had any influence on toxicity. CONCLUSIONS: The occurrence and subsequent correction of implant displacements exceeding 3 mm during fractionated HDR-BT monotherapy for PCa did not lead to increased incidences of acute or late GU and GI toxicity. This indicates that our clinical protocol to correct displacements > 3 mm results in safe treatment regarding organ at risk toxicity. PMID- 27364872 TI - The "decay" of brachytherapy use in tumors of the oral cavity: A population-based patterns of care and outcomes analysis from 1973 to 2012. AB - PURPOSE: We aimed to evaluate if use of brachytherapy (BT) is associated with improved survival in patients with oral cavity cancer who do not receive surgery and to analyze patterns of care. METHODS AND MATERIALS: We queried the Surveillance, Epidemiology, and End Results database for patients who received radiation therapy for squamous cell carcinoma of the oral cavity between 1973 and 2012. Patients were grouped by treatment modality: external beam radiotherapy alone vs. external beam radiotherapy + BT. Surgical patients were excluded. Trends in BT utilization over the study period and patterns of care were analyzed. Propensity scores were generated, and a nearest-neighbor matching algorithm was used to balance the 2 groups. Cox regression modeling was used to estimate the effect of BT on overall survival. Sensitivity analysis was conducted to estimate the effect of unmeasured confounders on the analysis. RESULTS: Of 5,161 patients with squamous cell carcinoma of the oral cavity who received radiotherapy, 12% of patients received BT. The rate of BT use has decreased by 0.58% per year (p < 0.001). Factors that predicted for omission of radiation therapy included age >= 65 years (adjusted odds ratio [aOR], 0.56; p < 0.001), regional nodal disease (aOR, 0.57; p < 0.001), and black race (aOR, 0.45; p < 0.001). Use of BT was associated with a decreased risk of death (hazard ratio, 0.75; p < 0.001). CONCLUSIONS: The use of BT is associated with improved survival in oral cavity tumors treated with definitive radiotherapy. Rates of BT utilization have declined by 0.58% per year and are currently very low. PMID- 27364873 TI - A consensus-based, process commissioning template for high-dose-rate gynecologic treatments. AB - PURPOSE: There is a lack of prescriptive, practical information for those doing the work of commissioning high-dose-rate (HDR) gynecologic (GYN) treatment equipment. The purpose of this work is to develop a vendor-neutral, consensus based, commissioning template to improve standardization of the commissioning process. METHODS AND MATERIALS: A series of commissioning procedures and tests specific to HDR GYN treatments were compiled within one institution. The list of procedures and tests was then sent to five external reviewers at clinics engaged in HDR GYN treatments. External reviewers were asked to (1) suggest deletions, additions, and improvements/modifications to descriptions, (2) link the procedures and tests to common, severe failure modes based on their effectiveness at mitigating those failure modes, and (3) rank the procedures and tests based on perceived level of importance. RESULTS: External reviewers suggested the addition of 14 procedures and tests. The final template consists of 67 procedures and tests. "Treatment process" and "staff training" sections were identified as mitigating the highest number of commonly reported failure modes. The mean perceived importance for all procedures and tests was 4.4 of 5, and the mean for each section ranged from 3.6 to 4.8. Sections of the template that were identified as mitigating the highest number of commonly reported failure modes were not assigned the highest perceived importance. CONCLUSION: The commissioning template developed here provides a standardized approach to process and equipment commissioning. The discord between perceived importance and mitigation of the highest number of failure modes suggests that increased focus should be placed on procedures and tests in "treatment process" and "staff training" sections. PMID- 27364874 TI - The nuances of brachytherapy taught by teachers from beyond: Questionnaire-based assessment of the first cadaveric hands-on brachytherapy workshop in India. AB - PURPOSE: A questionnaire-based assessment of a cohort of young radiation oncologists attending the first human cadaveric hands-on brachytherapy workshop in India. METHODS AND MATERIALS: The cadaveric workshop for hands-on training in head/neck and gynecologic cancers was a novel process conducted at M.S. Ramaiah Medical College and Hospital, for which 30 attendees from all regions of India took part with an opportunity to interact with experienced resource persons, individually perform the procedure, and indulge in all aspects of brachytherapy process. The questionnaire was part of the workshop and enquired on common practices for head/neck and gynecologic brachytherapy followed by the attendees at their hospitals and their opinion on avenues for learning the skill of brachytherapy and its future as a therapeutic modality. RESULTS: Twenty-seven of thirty attendees were practicing brachytherapy at their centers out of which only 14 (46%) were doing head/neck brachytherapy. In gynecologic procedures, 89% were performing only intracavitary brachytherapy. Twenty attendees (66%) felt lack of expertise was the primary reason for dwindling brachytherapy practice in India. Ten (33%) of them felt that advancements in external radiotherapy were the second major cause for it. Some less important reasons given were lack of suitable cases, fear of toxicity, and reduced remuneration. CONCLUSIONS: Cadaveric brachytherapy workshops may be a practical and cost-effective method to inculcate this unique skill set in the next generation of radiation oncologists. This questionnaire-based assessment has tried to validate this opinion. PMID- 27364875 TI - Measurement of extracellular volume and transit time heterogeneity using contrast enhanced myocardial perfusion MRI in patients after acute myocardial infarction. AB - PURPOSE: To assess the ability of dynamic contrast-enhanced myocardial perfusion MRI to measure extracellular volume (ECV) and to investigate the possibility of estimating capillary transit time heterogeneity (CTH) in patients after myocardial infarction and successful revascularization. METHODS: Twenty-four perfusion data sets were acquired on a 3 Tesla positron emission tomography (PET)/MRI scanner. Three perfusion models of different complexity were implemented in a hierarchical fashion with an Akaike information criterion being used to determine the number of fit parameters supported by the data. Results were compared sector-wise to ECV from an equilibrium T1 mapping method (modified look-locker inversion recovery (MOLLI)). RESULTS: ECV derived from the perfusion analysis correlated well with equilibrium measurements (R2 = 0.76). Estimation of CTH was supported in 16% of sectors (mostly remote). Inclusion of a nonzero CTH parameter usually led to lower estimates of first-pass extraction and slightly higher estimates of blood volume and flow. Estimation of the capillary permeability-surface area product was feasible in 81% of sectors. CONCLUSION: Transit time heterogeneity has a measurable effect on the kinetic analysis of myocardial perfusion MRI data, and Gd-DTPA extravasation in the myocardium is usually not flow-limited in infarct-related pathology. Measurement of myocardial ECV using perfusion imaging could provide a scan-time efficient alternative to methods based on T1 mapping. Magn Reson Med 77:2320-2330, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27364877 TI - Erratum to: 'Purkinje cell injury, structural plasticity and fusion in patients with Friedreich's ataxia'. PMID- 27364878 TI - Assessing the performance of multiplexed tandem PCR for the diagnosis of pathogenic genotypes of Theileria orientalis using pooled blood samples from cattle. AB - Oriental theileriosis caused by multiple genotypes of Theileria orientalis is an important tick-borne disease of bovines. Here, we assessed the performance of an established multiplexed tandem PCR (MT-PCR) for the diagnosis of the two recognized, pathogenic genotypes (chitose and ikeda) of T. orientalis in cattle using pooled blood samples. We used a total of 265 cattle blood samples, which were divided into two groups according to previous MT-PCR results for individual samples. Samples in group 1 (n = 155) were from a herd with a relatively high prevalence of T. orientalis infection; and those in group 2 (n = 110) were from four herds with a low prevalence. For group 1, 31 and 15 batches of five- and ten pooled samples (selected at random), respectively, were formed. For group 2, 22 and 11 batches of five- and ten-pooled samples (selected at random), respectively, were formed. DNAs from individual pooled samples in each batch and group were then tested by MT-PCR. For group 1, the apparent prevalences estimated using the 31 batches of five-pooled samples (97%) and 15 batches of ten-pooled samples (100%) were significantly higher compared with individual samples (75%). For group 2, higher apparent prevalences (9% and 36%) were also recorded for the 22 and 11 batches of pooled samples, respectively, compared with individual samples (7%). Overall, the average infection intensity recorded for the genotypes of chitose and ikeda were considerably lower in pooled compared with individual samples. The diagnostic specificities of MT-PCR were estimated at 95% and 94%, respectively, when batches of five- and ten-pooled samples were tested, and 94% for individual samples. The diagnostic sensitivity of this assay was estimated at 98% same for all individual, five- and ten-pooled samples. This study shows that screening batches of five- and ten-pooled blood samples from cattle herds are similar to those obtained for individual samples, and, importantly, that the reduced cost for the testing of pooled samples represents a considerable saving to herd managers. PMID- 27364879 TI - Imported Thai patient with Zika virus to Taiwan: What else should be known and discussed? PMID- 27364876 TI - Association of anemia with functional and nutritional status in the German multicenter study "GeriAnaemie2013". AB - OBJECTIVES: Anemia and malnutrition are risk factors for frailty in older people but data from multicenter studies among German geriatric inpatients are lacking. This analysis evaluated data from the multicenter study "GerAnaemie2013" commissioned by the German Geriatric Society. PATIENTS AND METHODS: The study involved an analysis of the 579 geriatric inpatients recruited in the context of the German multicenter study "GeriAnaemie2013". Study parameters: Barthel index (BI), handgrip strength, nutritional data (e.g. loss of appetite, loss of weight and decreased food intake). INCLUSION CRITERIA: in-patient age >=70 years, exclusion criteria: current cancer disease or cancer-associated treatment. Anemia was defined according to the World Health Organization (WHO) criteria. RESULTS: The mean age of patients was 81.9 years, overall prevalence of anemia 55.1 %, mean hemoglobin (Hb) level 11.9 g/dl, average BI 50.8 points and 30.3 % of all patients were at risk of malnutrition. While univariate analysis revealed a significantly lower BI in anemic patients, this association was no longer seen in multivariate analysis. Regression analysis revealed that a drug intake of > 5 drugs/day doubles the chance of suffering from anemia with an adjusted odds ratio (OR) of 2.17 (confidence interval (CI) 1.28-3.68, p = 0.004) as well as a serum albumin level below 3.5 g/dl with an adjusted OR of 2.11 (range 1.40-3.19, p < 0.001). CONCLUSION: Polymedication and low serum albumin were independent risk factors for anemia in geriatric patients, probably reflecting disease severity. PMID- 27364880 TI - Three episodes of Kawasaki disease including one after the Pneumo 23 vaccine in a child with a family history of Kawasaki disease. PMID- 27364881 TI - Symptoms of Post-Traumatic Stress Disorder Among Young Children 2 Years After the Great East Japan Earthquake. AB - OBJECTIVE: The aim of this study was to investigate the prevalence of post traumatic stress disorder (PTSD) and its association with each traumatic experience among 5- to 8-year-old children 2 years after the Great East Japan Earthquake. METHOD: Children ages 5-8 years who were in selected preschool classes on March 11, 2011, in 3 prefectures affected by the earthquake and 1 prefecture that was unaffected, participated in the study (N=280). PTSD symptoms were assessed through questionnaires completed by caregivers and interviews by psychiatrists or psychologists conducted between September 2012 and May 2013 (ie, 1.5-2 years after the earthquake). RESULTS: Among children who experienced the earthquake, 33.8% exhibited PTSD symptoms. Of the different traumatic experiences, experiencing the earthquake and the loss of distant relatives or friends were independently associated with PTSD symptoms; prevalence ratios: 6.88 (95% confidence interval [CI]: 2.06-23.0) and 2.48 (95% CI: 1.21-5.08), respectively. CONCLUSION: Approximately 1 in 3 young children in the affected communities exhibited PTSD symptoms, even 2 years after the Great East Japan Earthquake. These data may be useful for preventing PTSD symptoms after natural disasters and suggest the importance of providing appropriate mental health services for children. (Disaster Med Public Health Preparedness. 2017;11:207 215). PMID- 27364882 TI - Iron oxide nanozyme catalyzed synthesis of fluorescent polydopamine for light-up Zn(2+) detection. AB - Fluorescent polydopamine (FPD) is an interesting material with excellent biocompatibility. However, its preparation is currently a lengthy and potentially dangerous process. We herein employ magnetic iron oxide (Fe3O4) nanoparticles as a peroxidase-mimicking nanozyme to produce FPD under mild conditions. Different from previous protocols using multiple steps with up to 6% (~2 M) H2O2, this preparation takes place in a single step with just 5 mM H2O2 at room temperature. The oxidized product shows excitation-wavelength-dependent emission peaks, similar to previous reports. The reaction kinetics, pH, temperature, and ionic strength are individually optimized. Among a diverse range of other nanomaterials tested, including Fe2O3, CeO2, CoO, Co3O4, NiO, TiO2, gold nanoparticles, and graphene oxide, Fe2O3 and graphene oxide yielded relatively weak emission, while the rest of the materials failed to produce FPD. The Fe3O4 nanoparticles retained ~90% catalytic activity even after ten cycles of synthesis. Finally, Zn(2+) can enhance the fluorescence of FPD under 360 nm excitation but not under 480 nm excitation, leading to a sensitive light-up sensor with a detection limit of 60 nM Zn(2+). Therefore, this work has demonstrated not only a novel use of nanozymes, but also an interesting application of FPD. PMID- 27364883 TI - Influence of robotic-assisted laparoscopic hysterectomy on vaginal cuff healing and brachytherapy initiation in endometrial carcinoma patients. AB - PURPOSE: The purpose of this study was to examine the impact of robotic-assisted laparoscopic hysterectomy (RALH) compared with total abdominal hysterectomy by laparotomy (TAH) on vaginal cuff healing in early-stage endometrial carcinoma patients receiving adjuvant intravaginal brachytherapy (IVBT). METHODS AND MATERIALS: We included 137 consecutive patients who underwent adjuvant IVBT without external beam radiation therapy or chemotherapy for stage I-II endometrial carcinoma. All patients underwent either RALH or TAH. Vaginal cuff healing status as assessed by inspection and palpation at initial evaluation by radiation oncology (VC1) was the primary outcome, with secondary outcomes including vaginal cuff healing status at first scheduled IVBT (VC2), time interval from hysterectomy to initiation of IVBT, and local recurrence. RESULTS: Among 137 patients, 74 (54.0%) underwent RALH and 63 (46.0%) underwent TAH. There was no significant difference in mean time from hysterectomy to initial radiation oncology evaluation between RALH and TAH patients (approximately 30 days in both groups). RALH was the only covariate associated with protracted vaginal cuff healing time at both VC1 (P = .003) and VC2 (P = .038). There was a significantly increased mean interval between hysterectomy and start of IVBT for patients undergoing RALH from 47.7 to 55.0 days (P < .001). Vaginal cuff healing was more likely to contribute to delay in delivery of IVBT in RALH patients, whereas abdominal or other nonvaginal wound healing was more likely to contribute to delay in TAH patients. There were no vaginal cuff recurrences detected after 16 months median follow-up. CONCLUSIONS: RALH for early-stage endometrial carcinoma was associated with longer vaginal cuff healing time and a mean increase in interval from hysterectomy to IVBT of 1 week compared with TAH. PMID- 27364884 TI - ROS signalling in a destabilised world: A molecular understanding of climate change. AB - Climate change results in increased intensity and frequency of extreme abiotic and biotic stress events. In plants, reactive oxygen species (ROS) accumulate in proportion to the level of stress and are major signalling and regulatory metabolites coordinating growth, defence, acclimation and cell death. Our knowledge of ROS homeostasis, sensing, and signalling is therefore key to understanding the impacts of climate change at the molecular level. Current research is uncovering new insights into temporal-spatial, cell-to-cell and systemic ROS signalling pathways, particularly how these affect plant growth, defence, and more recently acclimation mechanisms behind stress priming and long term stress memory. Understanding the stabilising and destabilising factors of ROS homeostasis and signalling in plants exposed to extreme and fluctuating stress will concomitantly reveal how to address future climate change challenges in global food security and biodiversity management. PMID- 27364885 TI - A prospective multicenter evaluation of direct molecular detection of blood stream infection from a clinical perspective. AB - BACKGROUND: Rapid diagnosis and appropriate antimicrobial therapy are of major importance to decrease morbidity and mortality in patients with blood stream infections (BSI). Blood culture, the current gold standard for detecting bacteria in blood, requires at least 24-48 hours and has limited sensitivity if obtained during antibiotic treatment of the patient. The aim of this prospective multicenter study was to clinically evaluate the application of a commercial universal 16S/18S rDNA PCR, SepsiTestTM (PCR-ST), directly on whole blood. METHODS: In total 236 samples from 166 patients with suspected sepsis were included in the study. PCR-ST results were compared to blood culture, the current gold standard for detecting BSI. Because blood cultures can give false-negative results, we performed an additional analysis to interpret the likelihood of bloodstream infection by using an evaluation based on clinical diagnosis, other diagnostic tests and laboratory parameters. RESULTS: Clinical interpretation of results defined the detected organism to be contaminants in 22 of 43 positive blood cultures (51.2 %) and 21 of 47 positive PCR-ST results (44.7 %). Excluding these contaminants resulted in an overall sensitivity and specificity of the PCR ST of 66.7 and 94.4 % respectively. Of the 36 clinically relevant samples, 11 BSI were detected with both techniques, 15 BSI were detected with PCR-ST only and 10 with blood culture only. Therefore, in this study, SepsiTestTM detected an additional 71 % BSI compared to blood culture alone. CONCLUSIONS: More clinically relevant BSI were diagnosed by molecular detection, which might influence patient treatment. An improved SepsiTestTM assay suited for routine use can have additional value to blood culture in diagnosing bacteremia in septic patients. PMID- 27364887 TI - Reporting Guidelines for the Use of Expert Judgement in Model-Based Economic Evaluations. AB - INTRODUCTION: Expert judgement has a role in model-based economic evaluations (EEs) of healthcare interventions. This study aimed to produce reporting criteria for two types of study design to use expert judgement in model-based EE: (i) an expert elicitation (quantitative) study; and (ii) a Delphi study to collate (qualitative) expert opinion. METHODS: A two-round online Delphi process identified the degree of consensus for four core definitions (expert; expert parameter values; expert elicitation study; expert opinion) and two sets of reporting criteria in a purposive sample of experts. The initial set of reporting criteria comprised 17 statements for reporting a study to elicit parameter values and/or distributions and 11 statements for reporting a Delphi survey to obtain expert opinion. Fifty experts were invited to become members of the Delphi process panel by e-mail. Data analysis summarised the extent of agreement (using a pre-defined 75 % 'consensus' threshold) on the definitions and suggested reporting criteria. Free-text comments were analysed using thematic analysis. RESULTS: The final panel comprised 12 experts. Consensus was achieved for the definitions of expert (88 %); expert parameter values (83 %); and expert elicitation study (83 %). The panel recommended criteria to use when reporting an expert elicitation study (16 criteria) and a Delphi study to collate expert opinion (11 criteria). CONCLUSION: This study has produced guidelines for reporting two types of study design to use expert judgement in model-based EE: (i) an expert elicitation study requiring 16 reporting criteria; and (ii) a Delphi study to collate expert opinion requiring 11 reporting criteria. PMID- 27364888 TI - The role of kisspeptin and RFRP in the circadian control of female reproduction. AB - In female mammals, reproduction shows ovarian and daily rhythms ensuring that the timing of the greatest fertility coincides with maximal activity and arousal. The ovarian cycle, which lasts from a few days to a few weeks, depends on the rhythm of follicle maturation and ovarian hormone production, whereas the daily cycle depends on a network of circadian clocks of which the main one is located in the suprachiasmatic nuclei (SCN). In the last ten years, major progress has been made in the understanding of the neuronal mechanisms governing mammalian reproduction with the finding that two hypothalamic Arg-Phe-amide peptides, kisspeptin (Kp) and RFRP, regulate GnRH neurons. In this review we discuss the pivotal role of Kp and RFRP neurons at the interface between the SCN clock signal and GnRH neurons to properly time gonadotropin-induced ovulation. We also report recent findings indicating that these neurons may be part of the multi-oscillatory circadian system that times female fertility. Finally, we will discuss recent investigations indicating a role, and putative therapeutic use, of these neuropeptides in human reproduction. PMID- 27364889 TI - Betulinic acid ameliorates experimental diabetic-induced renal inflammation and fibrosis via inhibiting the activation of NF-kappaB signaling pathway. AB - Diabetic nephropathy (DN) is the leading cause of end-stage renal failure and is characterized by excessive deposition of extracellular matrix (ECM) proteins such as fibronectin (FN), in the glomerular mesangium and tubulointerstitium. Betulinic acid (BA), a pentacyclic triterpene derived from the bark of the white birch tree, has been demonstrated to have many pharmacological activities. However, the effect of BA on DN has not been fully elucidated. To explore the possible anti-inflammatory effects of BA and their underlying mechanisms, we used streptozotocin-induced diabetic rat kidneys and high glucose-treated glomerular mesangial cells. Our study showed BA could inhibit the degradation of IkappaBalpha and the activity of NF-kappaB in diabetic rat kidneys and high glucose-induced mesangial cells, resulting in reduction of FN expression. In addition, BA suppressed the DNA binding activity and transcriptional activity of NF-kappaB in high glucose-induced glomerular mesangial cells (GMCs). Furthermore, BA enhanced the interaction between IkappaBalpha and beta-arrestin2 in mesangial cells. Taken together, our data suggest BA inhibits NF-kappaB activation through stabilizing NF-kappaB inhibitory protein IkappaBalpha, thereby preventing diabetic renal fibrosis. PMID- 27364890 TI - Infiltrating T lymphocytes reduce myeloid phagocytosis activity in synucleinopathy model. AB - BACKGROUND: Synucleinopathies comprise a group of neurodegenerative diseases associated with abnormal accumulation of alpha-synuclein. One of the key factors that contribute to the progression of synucleinopathies is neuroinflammation. However, the role of lymphocytes in synucleinopathies like Parkinson's disease (PD) remains largely unclear. METHODS: To investigate how lymphocytes impact synucleinopathies, human wild-type alpha-synuclein (WTS) transgenic mice were crossed with mice lacking mature lymphocytes (Rag2(-/-)). In this in vivo model, we quantified alpha-synuclein aggregation in the substantia nigra (SN) and striatum and determined the numbers of innate and adaptive immune cells in the central nervous system (CNS). The activation state of resident and infiltrated CNS myeloid cells (M1 vs. M2) was further classified by gene and protein expression analyses. The impact of T and B lymphocytes on the phagocytic activity of microglia in the presence of alpha-synuclein aggregates was addressed in BV2 microglia in vitro. RESULTS: Compared to WTS(+) Rag2(+/+) mice, where T but not B lymphocytes infiltrated the CNS, decreased amounts of alpha-synuclein aggregates were found in WTS(+) Rag2(-/-) mice devoid of mature lymphocytes. The presence of T lymphocytes did not alter the number of Iba1(+) microglia but increased the frequency of the CD11b(+) CD45(hi) population in the CNS, indicative of an increased number of infiltrated macrophages. Moreover, the M1 phenotype was more prominent in WTS(+) Rag2(+/+) mice, whereas the M2 activation state was dominating in the absence of lymphocytes in WTS(+) Rag2(-/-) mice. In vitro, in the presence of T but not B lymphocytes, significantly less alpha-synuclein was phagocytosed by BV2 microglia, further supporting the prevalence of the M1 phenotype in the presence of T lymphocytes. CONCLUSIONS: Peripheral T lymphocytes strongly contribute to increased alpha-synuclein pathology via modulation of CNS myeloid cell function. In the presence of T lymphocytes, microglia phagocytosis of aggregated alpha-synuclein is reduced, which increases the severity of synucleinopathy. PMID- 27364891 TI - Robust Multiple-Range Coherent Quantum State Transfer. AB - We propose a multiple-range quantum communication channel to realize coherent two way quantum state transport with high fidelity. In our scheme, an information carrier (a qubit) and its remote partner are both adiabatically coupled to the same data bus, i.e., an N-site tight-binding chain that has a single defect at the center. At the weak interaction regime, our system is effectively equivalent to a three level system of which a coherent superposition of the two carrier states constitutes a dark state. The adiabatic coupling allows a well controllable information exchange timing via the dark state between the two carriers. Numerical results show that our scheme is robust and efficient under practically inevitable perturbative defects of the data bus as well as environmental dephasing noise. PMID- 27364892 TI - Stimulatory versus suppressive effects of GM-CSF on tumor progression in multiple cancer types. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF, also called CSF-2) is best known for its critical role in immune modulation and hematopoiesis. A large body of experimental evidence indicates that GM-CSF, which is frequently upregulated in multiple types of human cancers, effectively marks cancer cells with a 'danger flag' for the immune system. In this context, most studies have focused on its function as an immunomodulator, namely its ability to stimulate dendritic cell (DC) maturation and monocyte/macrophage activity. However, recent studies have suggested that GM-CSF also promotes immune-independent tumor progression by supporting tumor microenvironments and stimulating tumor growth and metastasis. Although some studies have suggested that GM-CSF has inhibitory effects on tumor growth and metastasis, an even greater number of studies show that GM-CSF exerts stimulatory effects on tumor progression. In this review, we summarize a number of findings to provide the currently available information regarding the anticancer immune response of GM-CSG. We then discuss the potential roles of GM-CSF in the progression of multiple types of cancer to provide insights into some of the complexities of its clinical applications. PMID- 27364894 TI - Pushing the limits of the Leksell stereotactic frame for spinal lesions up to C3: fixation at the maxilla. AB - BACKGROUND: Spinal radiosurgery is not considered in the domain of traditional Gamma Knife radiosurgery (GKRS) setup. The major obstacles in GKRS for upper cervical spine lesions remain in difficulty of frame fixation, avoiding collision and maintaining the integrity of the relative position of the lesion from image acquisition to treatment. METHODOLOGY: The supraorbital margin remains the standard lowest fixation point for Leksell stereotactic frame. We describe fixation at the maxilla to target and treat upper cervical spine lesions (up to C3 vertebra) with measures to ensure cervical immobilisation and precision of the GKRS treatment. RESULTS: We have treated two patients at the upper cervical spine up to C3 vertebra by fixing anterior pillars of the Leksell stereotactic frame at the maxilla. To ensure cervical immobilisation and precision of treatment, the neck was immobilised with a Philadelphia collar. The relative position between the head and sternum with the couch from image acquisition to the radiation delivery was kept constant. Docking angle was kept neutral (90 degrees) throughout the treatment (from image acquisition to actual treatment). CONCLUSIONS: The maxilla is a potential alternative for stereotactic frame fixation. Measures to ensure cervical immobilisation with lower-down frame position permits treatment of lesions as low as C3 vertebra. PMID- 27364893 TI - The role of autophagy in allergic inflammation: a new target for severe asthma. AB - Autophagy has been investigated for its involvement in inflammatory diseases, but its role in asthma has been little studied. This study aimed to explore the possible role of autophagy and its therapeutic potential in severe allergic asthma. BALB/c mice were sensitized with ovalbumin (OVA) on days 0 and 14, followed by primary OVA challenge on days 28-30. The mice received a secondary 1 or 2% OVA challenge on days 44-46. After the final OVA challenge, the mice were assessed for airway responsiveness (AHR), cell composition and cytokine levels in bronchoalveolar lavage fluid (BALF). LC3 expression in lung tissue was measured by western blot and immunofluorescence staining. Autophagosomes were detected by electron microscopy. 3-Methyladenine (3-MA) treatment and Atg5 knockdown were applied to investigate the potential role of autophagy in allergic asthma mice. AHR, inflammation in BALF and LC3 expression in lung tissue were significantly increased in the 2% OVA-challenged mice compared with the 1% OVA-challenged mice (P<0.05). In addition, eosinophils showed prominent formation of autophagosomes and increased LC3 expression compared with other inflammatory cells in BALF and lung tissue. After autophagy was inhibited by 3-MA and Atg5 shRNA treatment, AHR, eosinophilia, interleukin (IL)-5 levels in BALF and histological inflammatory findings were much improved. Finally, treatment with an anti-IL-5 antibody considerably reduced LC3 II expression in lung homogenates. Our findings suggest that autophagy is closely correlated with the severity of asthma through eosinophilic inflammation, and its modulation may provide novel therapeutic approaches for severe allergic asthma. PMID- 27364895 TI - Subarachnoid haemorrhage secondary to traumatic intracranial aneurysm of the posterior cerebral circulation: case series and literature review. AB - BACKGROUND: To identify the clinical features, rebleed risk, timing and method of diagnosis, complications and outcome for subarachnoid haemorrhage (SAH) from traumatic intracranial aneurysm (TICA) of the posterior circulation. Subjects included 26 patients aged 3-54 (mean 24.8). METHODS: Case series and literature search to identify all reported cases. RESULTS: In our series, two of three cases were fatal as a result of rebleed, and one case had a good outcome with no deficit, following prompt diagnosis and embolisation. Our key findings from the literature review were: 30.7 % of patients were age 16 and under; 88 % had an acute drop in consciousness, 46 % in a delayed manner; the mean time to diagnosis was 7.5 days; initial cerebrovascular imaging was normal in 23 %; the rebleed rate was 23 %; 61 % required emergency diversion of cerebrospinal fluid; 11 % developed vasospasm requiring treatment; 19.2 % had deficits that rendered them unable to live independently. The mortality rate was 27 %. CONCLUSIONS: SAH from ruptured posterior circulation TICA is associated with significant morbidity and mortality. A high index of suspicion as well as prompt diagnosis, repeat imaging in selected cases, and treatment of any associated TICA can be crucial to a favourable outcome. PMID- 27364896 TI - Severe Paracoccidioidomycosis in a 14-Year-Old Boy. AB - Paracoccidioidomycosis (PCM) is the most important systemic mycoses in Latin America. We describe a severe case of paracoccidioidomycosis in a 14-year-old boy, with a rapid disease progression. The fungal strain was isolated and inoculated into a T and/or B cell immunocompromised mice, which revealed a highly virulent strain. The case report presented herein emphasizes the importance of considering PCM in the differential diagnosis of patients with other infectious diseases in endemic areas and highlights a novel isolate. PMID- 27364897 TI - [Items that justify a day-care hospital stay for the management of skin cancer. Guidelines from the Oncodermatology Group of the Societe Francaise de Dermatologie]. PMID- 27364898 TI - [Criteria of the French bullous study group for day-care hospitalization billing for a patient with autoimmune bullous disease]. PMID- 27364899 TI - [The role of reflectance confocal microscopy and optical coherence tomography in the diagnosis of epithelial-cystic conjunctival nevus]. PMID- 27364900 TI - Single- and Multiple-Dose Pharmacokinetics of Immediate-Release/Extended-Release Ibuprofen Tablets. AB - A single-dose, randomized, open-label, crossover study (study 1; n = 35) and a multiple-dose, randomized, open-label, crossover study (study 2; n = 28) compared the pharmacokinetics of a new immediate-release/extended-release (IR/ER) bilayer tablet formulation of ibuprofen 600 mg every 12 hours with standard ibuprofen 200 mg IR every 4 hours. In both studies, the 2 formulations were bioequivalent to each other for the area under the plasma concentration-versus-time curve from time 0 to the last measurable concentration (AUCL), to infinity (AUCinfinity ), and to 12 hours (AUC0-12 ) and maximum concentration (Cmax ). In study 1, food slowed the absorption of ibuprofen from ibuprofen 600 mg IR/ER (lower Cmax ) compared with the fasted state but did not affect the overall extent (AUC) of ibuprofen absorption. In study 2, there was no evidence of drug accumulation with multiple doses of ibuprofen IR/ER. In conclusion, ibuprofen 600 mg IR/ER provides a twice-daily over-the-counter analgesic option that is bioequivalent to standard ibuprofen 200 mg IR (every 4 hours) with regard to both the rate (Cmax ) and the extent (AUC) of absorption. PMID- 27364901 TI - Off the Beaten Track-A Hitchhiker's Guide to Beryllium Chemistry. AB - This Minireview aims to give an introduction to beryllium chemistry for all less experienced scientists in this field of research. Up to date information on the toxicity of beryllium and its compounds are reviewed and several basic and necessary guidelines for a safe and proper handling in modern chemical research laboratories are presented. Interesting phenomenological observations are described that are related directly to the uniqueness of this element, which are also put into historical context. Herein we combine the contributions and experiences of many scientist that work passionately in this field. We want to encourage fellow scientists to reconcile the long-standing reservations about beryllium and its compounds and motivate intense research on this spurned element. Who on earth should be able to deal with beryllium and its compounds if not chemists? PMID- 27364902 TI - Tissue microarray profiling in human heart failure. AB - Tissue MicroArrays (TMAs) are a versatile tool for high-throughput protein screening, allowing qualitative analysis of a large number of samples on a single slide. We have developed a customizable TMA system that uniquely utilizes cryopreserved human cardiac samples from both heart failure and donor patients to produce formalin-fixed paraffin-embedded sections. Confirmatory upstream or downstream molecular studies can then be performed on the same (biobanked) cryopreserved tissue. In a pilot study, we applied our TMAs to screen for the expression of four-and-a-half LIM-domain 2 (FHL2), a member of the four-and-a half LIM family. This protein has been implicated in the pathogenesis of heart failure in a variety of animal models. While FHL2 is abundant in the heart, not much is known about its expression in human heart failure. For this purpose, we generated an affinity-purified rabbit polyclonal anti-human FHL2 antibody. Our TMAs allowed high-throughput profiling of FHL2 protein using qualitative and semiquantitative immunohistochemistry that proved complementary to Western blot analysis. We demonstrated a significant relative reduction in FHL2 protein expression across different forms of human heart failure. PMID- 27364903 TI - Differences in cytocompatibility, dynamics of the oxide layers' formation, and nickel release between superelastic and thermo-activated nickel-titanium archwires. AB - Superelastic (SE) and thermo-activated (TA) nickel-titanium (NiTi) archwires are used in everyday orthodontic practice, based on their acceptable biocompatibility and well-defined shape memory properties. However, the differences in their surface microstructure and cytotoxicity have not been clearly defined, and the standard cytotoxicity tests are too robust to detect small differences in the cytotoxicity of these alloys, all of which can lead to unexpected adverse reactions in some patients. Therefore, we tested the hypothesis that the differences in manufacture and microstructure of commercially available SE and TA archwires may influence their biocompatibility. The archwires were studied as received and after conditioning for 24 h or 35 days in a cell culture medium under static conditions. All of the tested archwires, including their conditioned medium (CM), were non-cytotoxic for L929 cells, but Rematitan SE (both as received and conditioned) induced the apoptosis of rat thymocytes in a direct contact. In contrast, TruFlex SE and Equire TA increased the proliferation of thymocytes. The cytotoxic effect of Rematitan SE correlated with the higher release of Ni ions in CM, higher concentration of surface Ni and an increased oxygen layer thickness after the conditioning. In conclusion, the apoptosis assay on rat thymocytes, in contrast to the less sensitive standard assay on L929 cells, revealed that Rematitan SE was less cytocompatible compared to other archwires and the effect was most probably associated with a higher exposition of the cells to Ni on the surface of the archwire, due to the formation of unstable oxide layer. PMID- 27364904 TI - Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib. AB - New targeted approaches to ovarian clear cell carcinomas (OCCC) are needed, given the limited treatment options in this disease and the poor response to standard chemotherapy. Using a series of high-throughput cell-based drug screens in OCCC tumor cell models, we have identified a synthetic lethal (SL) interaction between the kinase inhibitor dasatinib and a key driver in OCCC, ARID1A mutation. Imposing ARID1A deficiency upon a variety of human or mouse cells induced dasatinib sensitivity, both in vitro and in vivo, suggesting that this is a robust synthetic lethal interaction. The sensitivity of ARID1A-deficient cells to dasatinib was associated with G1-S cell-cycle arrest and was dependent upon both p21 and Rb. Using focused siRNA screens and kinase profiling, we showed that ARID1A-mutant OCCC tumor cells are addicted to the dasatinib target YES1. This suggests that dasatinib merits investigation for the treatment of patients with ARID1A-mutant OCCC. Mol Cancer Ther; 15(7); 1472-84. (c)2016 AACR. PMID- 27364905 TI - Developing a Peer-to-Peer mHealth Application to Connect Hispanic Cancer Patients. AB - Cancer and its treatment can significantly impact health-related quality of life (HRQOL) (J Pain Symptom Manag 9 (3):186-192, 1994; Soc Sci Med 46:1569-1584, 1998), particularly for Hispanics (Healthcare Financ Rev 29 (4):23-40, 2008; Psycho-Oncology 21 (2):115-124, 2012). Moreover, providers of cancer support for this population may encounter unique challenges. Grounded in social capital theory, this study identified Spanish-speaking, Hispanic breast cancer survivor support needs and preferences for a mHealth intervention. A user-centered, community-engaged research design was employed, consisting of focus groups made up of constituents from a local Hispanic-serving, cancer support organization. Focus group audio-recordings, translated into English, were coded using a grounded theory analytic approach. First, lead researchers read the complete transcripts to obtain a general sense of the discussion. Next, coding rules were established (e.g., code at the most granular level; double and triple code if necessary, code exhaustively) and initial codebook was created through open coding. Three new coders were trained to establish requisite kappa statistic levels (>=.70) for inter-rater reliability. With training and discussion, kappa estimates reached .81-.88. Focus group (n = 31) results revealed a mHealth intervention targeting Hispanic cancer patients should not only offer information and support on disease/treatment effects but also respond to the individual's HRQOL, particularly emotional and social challenges. Specifically, participants expressed a strong desire for Spanish content and to connect with others who had gone through a similar experience. Overall, participants indicated they would have access to and would use such an intervention. Findings indicate positive support for a mHealth tool, which is culturally tailored to Spanish speakers, is available in Spanish, and connects cancer patients with survivors. PMID- 27364907 TI - Injuries sustained in National Collegiate Athletic Association men's and women's basketball, 2009/2010-2014/2015. AB - BACKGROUND/AIM: Recent rule changes regarding the safety of basketball athletes necessitate up-to-date reports of injury incidence. This study describes the epidemiology of injuries in men's and women's National Collegiate Athletic Association (NCAA) basketball during the 2009/2010-2014/2015 seasons. METHODS: Basketball injury data originate from the 2009/2010-2014/2015 academic years from the NCAA Injury Surveillance Program (NCAA-ISP) from 78 men's and 74 women's NCAA basketball programmes which provided 176 and 181 team-seasons, respectively. A reportable injury occurred during organised practice or competition and required attention from an athletic trainer (AT) or physician. Injury rates, injury proportions and rate ratios (RRs) were calculated. All 95% CIs not containing 1.0 were considered statistically significant. RESULTS: A total of 2308 and 1631 injuries were reported in men's and women's basketball, respectively, for injury rates of 7.97 and 6.54/1000 athlete-exposures (AEs). The rate was higher in men than women (RR=1.22; 95% CI 1.15 to 1.30). Non-time-loss (NTL) injuries (resulting in participation restriction time under 24 hours) accounted for 64.8% and 53.6% of men's competition and practice injuries, respectively, and 53.9% and 51.3% of women's competition and practice injuries, respectively. Injuries to the lower extremity were the most common in competitions (men: 54.9%; women: 59.0%) and practices (men: 62.4%; women: 67.3%). The most common injury in men's and women's basketball was ankle sprain (17.9% and 16.6%, respectively). CONCLUSIONS: NTL injuries account for over half of all injuries in basketball. Most injuries were lower extremity injuries, specifically ankle sprains. While rule changes have been implemented to make basketball safer, continued research is needed to assess the effectiveness of these changes. PMID- 27364906 TI - Rituximab is not a "magic drug" in post-transplant recurrence of nephrotic syndrome. AB - Pediatric patients with end-stage renal failure due to severe drug-resistant nephrotic syndrome are at risk of rapid recurrence after renal transplantation. Treatment options include plasmapheresis, high-dose of cyclosporine A/methylprednisolone and more recently-rituximab (anti-B CD20 monoclonal depleting antibody). We report five patients with immediate (1-2 days) post transplant recurrence of nephrotic syndrome, treated with this kind of combined therapy including 2-4 weekly doses of 375 mg/m(2) of rituximab. Only two (of five) patients have showed full long-term remission, while the partial remission was seen in two cases, and no clinical effect at all was achieved in one patient. The correlation between B CD19 cells depletion and clinical effect was present in two cases only. Severe adverse events were present in two patients, including one fatal rituximab-related acute lung injury. CONCLUSION: The anti-CD20 monoclonal antibody may be not effective in all pediatric cases of rapid post-transplant recurrence of nephrotic syndrome, and benefit/risk ratio must be carefully balanced on individual basis before taking the decision to use this protocol. WHAT IS KNOWN: * nephrotic syndrome may recur immediately after renal transplantation * plasmapheresis combined with pharmacotherapy is used as rescue management * rituximab was reported as effective drug both in primary and post transplant nephrotic syndrome What is New: * rituximab may not be effective is several cases of post-transplant nephrotic syndrome due to variety of underlying mechanisms of the disease, which may be or not be responsive to this drug * there may be no correlation between drug-induced depletion of specific B cells and clinical effect; this might suggest B-cell independent manner of rituximab action. PMID- 27364908 TI - Guidelines on venous ulceration: A mess. PMID- 27364909 TI - [Fasciae latae perforator flap for breast reconstruction: An attractive alternative in case of DIEP contraindication]. AB - The musculocutaneous tensor fascia latae flap was one of the first free flaps described. It is possible to harvest a flap with the same skin paddle, vascularized by a septo-cutaneous perforator running through the tensor fascia lata muscle septum and coming from the ascending branch of the lateral circumflex femoral artery. The DIEP is currently the workhorse of autologous breast reconstruction, but there are some contraindications. The septo-cutaneous tensor fascia latae perforator flap may be an alternative for women with lateral upper thigh lipodystrophy. Between 2010 and 2014, three flaps have been performed in two patients for delayed breast reconstruction (one case of unilateral reconstruction, and one bilateral). Perforators were identified by preoperative angiography. The intervention was performed in a two-team approach, in only one operative position. Perforators were located in the horizontal axis of the upper rim of the pubis bone. One perforator artery was dissected for each flap. The mean caliber of the pedicle was 2.8mm, and the mean length was 6.4cm. The operative time was 240minutes for unilateral flap, 375minutes for bilateral flap. There was no case of total or partial necrosis, or complications on the donor site. Cosmetic results were considered satisfying by patients and surgeons with the reconstructed breast as well as the donor site. Septo-cutaneous fascia lata perforator flap is an attractive flap for breast reconstruction in patients with DIEP contraindication and lateral upper thigh lipodystrophy. It has many advantages: easy to harvest, length and calibre of the pedicle, double team approach, only one operating position, quality of reconstruction. It is necessary to carry out a larger series of cases to study the complication rate in the donor site. PMID- 27364910 TI - Unusual case of appendicitis. AB - A teenage girl was admitted to the paediatric assessment unit with non-specific abdominal pain that gradually localised to the right iliac fossa (RIF). She remained systemically well; investigations including blood tests, urine sample and abdominal ultrasound were inconclusive. Surgical opinion was sought and the decision was made to perform a diagnostic laparoscopy due to the ongoing pain. Laparoscopy showed no evidence of any significant pathology, and appendicectomy was performed following the routine practice. Numerous pinworms came out while the appendix was resected. The RIF pain resolved and the patient made a full post operative recovery. A stat dose of mebendazole and amoxicillin were given and the immediate family was also treated. Enterobius vermicularis (pinworm) causes significant morbidity worldwide and has a high prevalence among children in the UK. It can be easily treated and prompt recognition based on clinical symptoms can potentially prevent unnecessary surgery. PMID- 27364911 TI - FGF21 represses cerebrovascular aging via improving mitochondrial biogenesis and inhibiting p53 signaling pathway in an AMPK-dependent manner. AB - Cerebrovascular aging has a high relationship with stroke and neurodegenerative disease. In the present study, we evaluated the influence of fibroblast growth factor 21 (FGF21) on angiotensin (Ang II)-mediated cerebrovascular aging in human brain vascular smooth muscle cells (hBVSMCs). Ang II induced remarkable aging phenotypes in hBVSMCs, including enhanced SA-beta-gal staining and NBS1 protein expression. First, we used immunoblotting assay to confirm protein expression of FGF21 receptor (FGFR1) and the co-receptor beta-Klotho in cultured hBVSMCs. Second, we found that FGF21 treatment partly prevented the aging-related changes induced by Ang II. FGF21 inhibited Ang II-enhanced ROS production/superoxide anion levels, rescued the Ang II-reduced Complex IV and citrate synthase activities, and suppressed the Ang II-induced meprin protein expression. Third, we showed that FGF21 not only inhibited the Ang II-induced p53 activation, but also blocked the action of Ang II on Siah-1-TRF signaling pathway which is upstream factors for p53 activation. At last, either chemical inhibition of AMPK signaling pathway by a specific antagonist Compound C or knockdown of AMPKalpha1/2 isoform using siRNA, successfully abolished the anti-aging action of FGF21 in hBVSMCs. These results indicate that FGF21 protects against Ang II induced cerebrovascular aging via improving mitochondrial biogenesis and inhibiting p53 activation in an AMPK-dependent manner, and highlight the therapeutic value of FGF21 in cerebrovascular aging-related diseases such as stroke and neurodegenerative disease. PMID- 27364912 TI - Vitamin D prevents glycation of proteins: an in vitro study. AB - Human serum albumin (HSA) is an important protein involved in the transport of hormones, fatty acids, drugs, and other macromolecules. Under hyperglycemic conditions, this molecule undergoes irreversible modification that affects its structure and function. In this study, we explored the effect of two forms of vitamin D, a nutraceutical, on glycation modification in HSA. The protein was incubated with a physiologically high concentration of glucose in the presence of vitamin D metabolites. After 21 days, samples were tested for secondary structural changes, side chain modification, and the presence of advanced glycation end products. Vitamin D metabolites could reduce glycation modification, albeit only to a small extent. Interaction studies reveal that Vitamin D interaction with HSA can prevent protein glycation. PMID- 27364913 TI - Implementation of an educational program for nursing students amidst the Ebola virus disease epidemic. AB - BACKGROUND: The global Ebola virus disease (EVD) epidemic of 2014/2015 prompted faculty at Emory University to develop an educational program for nursing students to increase EVD knowledge and confidence and decrease concerns about exposure risk. PURPOSE: The purpose of this article is to describe the development, implementation, and evaluation of the EVD Just-in-Time Teaching (JiTT) educational program. METHODS: Informational sessions, online course links, and a targeted, self-directed slide presentation were developed and implemented for the EVD educational program. Three student surveys administered at different time points were used to evaluate the program and change in students' EVD knowledge, confidence in knowledge, and risk concern. DISCUSSION: Implementation of a JiTT educational program effectively achieved our goals to increase EVD knowledge, decrease fear, and enhance student confidence in the ability to discuss EVD risk. These achievements were sustained over time. CONCLUSION: JiTT methodology is an effective strategy for schools of nursing to respond quickly and comprehensively during an unanticipated infectious disease outbreak. PMID- 27364916 TI - A Developmental and Process Approach to "Choice Categories": Imagination and "Tacit Knowledge". AB - A developmental process approach is proposed in order to contribute to reflect upon "choice categories" as the phenomena of human individuation (Mammen and Mironenko, Integrative Psychological and Behavioral Science, 49:681-713, 2015; Mammen, 2016). Firstly we contrapose this perspective to the results referred by Krojgaard (Integrative Psychological & Behavioral Science, 50(2), 264-276, 2016) regarding infant development. Subsequently, we discuss the role of imagination and the role of Polanyi's "tacit knowledge" as contributing to complement the concept of "choice categories". By this way we aim to highlight the heuristic value of focusing on the quality of the dynamics that guide developmental changes and its embeddedness in sociocultural milieu. PMID- 27364915 TI - A high-density SNP genotyping array for Brassica napus and its ancestral diploid species based on optimised selection of single-locus markers in the allotetraploid genome. AB - KEY MESSAGE: The Brassica napus Illumina array provides genome-wide markers linked to the available genome sequence, a significant tool for genetic analyses of the allotetraploid B. napus and its progenitor diploid genomes. A high-density single nucleotide polymorphism (SNP) Illumina Infinium array, containing 52,157 markers, was developed for the allotetraploid Brassica napus. A stringent selection process employing the short probe sequence for each SNP assay was used to limit the majority of the selected markers to those represented a minimum number of times across the highly replicated genome. As a result approximately 60 % of the SNP assays display genome-specificity, resolving as three clearly separated clusters (AA, AB, and BB) when tested with a diverse range of B. napus material. This genome specificity was supported by the analysis of the diploid ancestors of B. napus, whereby 26,504 and 29,720 markers were scorable in B. oleracea and B. rapa, respectively. Forty-four percent of the assayed loci on the array were genetically mapped in a single doubled-haploid B. napus population allowing alignment of their physical and genetic coordinates. Although strong conservation of the two positions was shown, at least 3 % of the loci were genetically mapped to a homoeologous position compared to their presumed physical position in the respective genome, underlying the importance of genetic corroboration of locus identity. In addition, the alignments identified multiple rearrangements between the diploid and tetraploid Brassica genomes. Although mostly attributed to genome assembly errors, some are likely evidence of rearrangements that occurred since the hybridisation of the progenitor genomes in the B. napus nucleus. Based on estimates for linkage disequilibrium decay, the array is a valuable tool for genetic fine mapping and genome-wide association studies in B. napus and its progenitor genomes. PMID- 27364917 TI - Correction: Sparse sampling methods in multidimensional NMR. AB - Correction for 'Sparse sampling methods in multidimensional NMR' by Mehdi Mobli et al., Phys. Chem. Chem. Phys., 2012, 14, 10835-10843. PMID- 27364918 TI - NURSE STAFFING AND RENAL ANAEMIA OUTCOMES IN HAEMODIALYSIS CARE. AB - BACKGROUND: Current trends in renal anaemia management place greater emphasis, and thus increased workload, on the role of the nurse in haemodialysis settings. However, there is little evidence that demonstrates the relationship between nurse staffing and patient outcomes. OBJECTIVES: To describe nurse staffing in haemodialysis settings, its relationship with target levels of renal anaemia management and to describe target level achievement for different ways of organising anaemia management. DESIGN: Cross-sectional audit. PARTICIPANTS: Forty (out of 78) haemodialysis centres in Sweden reported quality assurance data. MEASUREMENTS: The numbers of bedside registered nurses, licensed nurse assistants and patients undergoing haemodialysis during a predefined morning shift; type of anaemia management and achieved target levels of anaemia management. RESULTS: The mean patient:registered nurse ratio was 2.4 and the mean patient:nurse assistant ratio was 12.8. There were no significant relationships between registered nurse staffing and target level achievement. On average, 45.6% of the patients had haemoglobin within the target levels at centres applying nurse-driven anaemia management, compared with 47.3% at physician-driven centres. CONCLUSIONS: These cross-sectional data suggest that renal anaemia outcomes are unrelated to the patient:registered nurse ratio. There is, however, room for improvement in renal anaemia management in the units included in this study, particularly the achievement of target levels of haemoglobin and transferrin saturation. PMID- 27364919 TI - Expression of pluripotency markers in Arbas Cashmere goat hair follicle stem cells. AB - In our previous work, we found that the Inner Mongolia Arbas Cashmere goat hair follicle stem cells (gHFSCs) can be successfully differentiated into adipocyte, chondrocyte, and osteocyte lineages. In this study, we further examined the expression of the pluripotency and stemness markers Oct4, Nanog, Sox2, AKP, and TERT in gHFSCs by immunocytochemistry, flow cytometry, real-time PCR, and Western blot. Immunofluorescent staining showed that the gHFSCs were positive for all five markers. Fluorescence-activated cell sorting (FACS) further analyzed the positive expression of Oct4, Nanog, and Sox2 in the gHFSCs. Compared with Arbas Cashmere goat adipose-derived stem cells (gADSCs) at the mRNA expression level, Oct4 was relatively highly expressed in gHFSCs, 41.36 times of the gADSCs, and Nanog was 5.61, AKP was 2.74, and TERT was 2.10 times, respectively (p < 0.01). Western blot indicated that all markers are expressed at the protein level in the gHFSCs. When compared with gADSCs, using alpha-tubulin as a reference protein, gray intensity analysis showed that the expression of Oct4, Nanog, AKP, and TERT were, respectively, 5.94, 10.78, 1.33, and 1.39 times of gADSCs. Additionally, mRNA and protein expression of Sox2 were detected in the gHFSCs but not in the gADSCs. The protein expression pattern of these markers was consistent with the mRNA results. PMID- 27364921 TI - Mapping intra-urban transmission risk of dengue fever with big hourly cellphone data. AB - Cellphone tracking has been recently integrated into risk assessment of disease transmission, because travel behavior of disease carriers can be depicted in unprecedented details. Still in its infancy, such an integration has been limited to: 1) risk assessment only at national and provincial scales, where intra-urban human movements are neglected, and 2) using irregularly logged cellphone data that miss numerous user movements. Furthermore, few risk assessments have considered positional uncertainty of cellphone data. This study proposed a new framework for mapping intra-urban disease risk with regularly logged cellphone tracking data, taking the dengue fever in Shenzhen city as an example. Hourly tracking records of 5.85 million cellphone users, combined with the random forest classification and mosquito activities, were utilized to estimate the local transmission risk of dengue fever and the importation risk through travels. Stochastic simulations were further employed to quantify the uncertainty of risk. The resultant maps suggest targeted interventions to maximally reduce dengue cases exported to other places, as well as appropriate interventions to contain risk in places that import them. Given the popularity of cellphone use in urbanized areas, this framework can be adopted by other cities to design spatio temporally resolved programs for disease control. PMID- 27364920 TI - Haptoglobin increases the vulnerability of CD163-expressing neurons to hemoglobin. AB - Haptoglobin (Hp) binds hemoglobin (Hb) with high affinity and provides the primary defense against its toxicity after intravascular hemolysis. Neurons are exposed to extracellular Hb after CNS hemorrhage, and a therapeutic effect of Hp via Hb sequestration has been hypothesized. In this study, we tested the hypothesis that Hp protects neurons from Hb in primary mixed cortical cell cultures. Treatment with low micromolar concentrations of human Hb for 24 h resulted in loss of 10-20% of neurons without injuring glia. Concomitant treatment with Hp surprisingly increased neuronal loss five-sevenfold, with similar results produced by Hp 1-1 and 2-2 phenotypes. Consistent with a recent in vivo observation, neurons expressed the CD163 receptor for Hb and the Hb-Hp complex in these cultures. Hp reduced overall Hb uptake, directed it away from the astrocyte-rich CD163-negative glial monolayer, and decreased induction of the iron-binding protein ferritin. Hb-Hp complex neuronal toxicity, like that of Hb per se, was iron-dependent and reduced by deferoxamine and 2,2' bipyridyl. These results suggest that Hp increases the vulnerability of CD163+ neurons to Hb by permitting Hb uptake while attenuating the protective response of ferritin induction by glial cells. Cover Image for this issue: doi: 10.1111/jnc.13342. PMID- 27364922 TI - Oral delivery of insulin for treatment of diabetes: status quo, challenges and opportunities. AB - OBJECTIVES: Diabetes mellitus is characterised by progressive beta-cell destruction and loss of function, or loss of ability of tissues to respond to insulin. Daily subcutaneous insulin injection is standard management for people with diabetes, although patient compliance is hard to achieve due to the inconvenience of injections, so other forms of delivery are being tested, including oral administration. This review summarises the developments in oral insulin administration. METHODS: The PubMed database was consulted to compile this review comparing conventional subcutaneous injection of insulin to the desired oral delivery. KEY FINDINGS: Oral administration of insulin has potential benefits in reducing pain and chances of skin infection, improving the portal levels of insulin and avoiding side effects such as hyperinsulinemia, weight gain and hypoglycaemia. Although oral delivery of insulin is an ideal administration route for patients with diabetes, several physiological barriers have to be overcome. An expected low oral bioavailability can be attributed to its high molecular weight, susceptibility to enzymatic proteolysis and low diffusion rate across the mucin barrier. CONCLUSIONS: Strategies for increasing the bioavailability of oral insulin include the use of enzyme inhibitors, absorption enhancers, mucoadhesive polymers and chemical modification for endogenous receptor-mediated absorption. These may help significantly increase patient compliance and disease management. PMID- 27364924 TI - Lengthening temporalis myoplasty versus free muscle transfer with the gracilis flap for long-standing facial paralysis: A systematic review of outcomes. AB - BACKGROUND: Our aim was to compare the outcomes of reconstructive surgery for long-standing facial paralysis by gracilis free flap transfer versus lengthening temporalis myoplasty (LTM) according to Daniel Labbe. MATERIALS AND METHODS: PubMed, Web of Science, Wiley Online Library, Cochrane Library, Directory of Open Access Journals, and SAGE Premier 2011 database were electronically searched. Randomized controlled trials (RCTs), controlled clinical trials (CCTs), and case series with a sample size > 5 were sought. Data were extracted by a single investigator. RESULTS: Sixteen articles met the selection criteria. All of these studies were retrospective case series. Efficacy outcomes were analyzed by assessing mouth symmetry both at rest and upon smiling, as well as the quality and the spontaneanity of the smile. Commissural displacement in patients operated by the gracilis flap was greater after surgery involving masseteric nerve reinnervation than a cross-facial nerve graft reinnervation. Patients with double innervation had similar results to those who had surgery involving only masseteric nerve reinnervation. These results are in accordance with the subjective evaluations. Patients operated by the lengthening temporalis myoplasty achieve less lateral movement of the commissure, with controversial evidence of spontaneity (only "automatic"). CONCLUSIONS: There are currently no published RCTs or CCTs regarding facial reanimation surgery. Thus, only very weak evidence is available to support the use of one type of surgery over another. However, our review suggests that LTM achieves results that are at least equal to those obtained with gracilis transfer, but LTM is a less extensive procedure that provides quicker results without the need for more than one operation. LTM, therefore, seems a good alternative to free muscle flap. LEVEL OF EVIDENCE: IV. PMID- 27364923 TI - TRPV1-mediated presynaptic transmission in basolateral amygdala contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation. AB - The central mechanisms of visceral hypersensitivity remain largely unknown. It's reported that there are highest densities of TRPV1 labeled neurons within basolateral amygdala (BLA). The aim of this study was to explore the role and mechanisms of TRPV1 in BLA in development of visceral hypersensitivity. Visceral hypersensitivity was induced by neonatal maternal deprivation (NMD) and was quantified by abdominal withdrawal reflex. Expression of TRPV1 was determined by Western blot. The synaptic transmission of neurons in BLA was recorded by patch clamping. It was found that the expression of TRPV1 in BLA was significantly upregulated in NMD rats; glutamatergic synaptic activities in BLA were increased in NMD rats; application of capsazepine (TRPV1 antagonist) decreased glutamatergic synaptic activities of BLA neurons in NMD slices through a presynaptic mechanism; application of capsaicin (TRPV1 agonist) increased glutamatergic synaptic activities of BLA neurons in control slices through presynaptic mechanism without affecting GABAergic synaptic activities; microinjecting capsazepine into BLA significantly increased colonic distension threshold both in control and NMD rats. Our data suggested that upregulation of TRPV1 in BLA contributes to visceral hypersensitivity of NMD rats through enhancing excitation of BLA, thus identifying a potential target for treatment of chronic visceral pain. PMID- 27364925 TI - Clinical characteristics of adverse events associated with therapeutic monoclonal antibodies in Korea. AB - PURPOSE: The use of monoclonal antibodies (mAbs) is increasing in various clinical fields. Although mAb safety must be demonstrated prior to approval, targeted pharmacovigilance is essential for the recognition and assessment of adverse reactions. The purpose of this study was to identify the major clinical features of adverse reactions to mAbs in Korea. METHODS: Spontaneous reports of adverse reactions attributed to 18 mAbs from January 2005 to December 2014 were extracted from the Korea Adverse Event Reporting System. We analyzed these reports for information relating to patient characteristics and the types of adverse reactions. RESULTS: In total, 11 492 adverse reactions were reported in 7569 patients. Almost 19% of total study population showed suspected hypersensitivity reactions. Leukocyte abnormalities were reported frequently (10.0%), as well as infections (9.5%), drug eruptions (7.5%), and pruritus (5.0%). Furthermore, 3716 of the adverse reactions in 2538 patients were classified as serious; these included severe infections (18.2%), neutropenia (12.1%), visual dysfunctions (6.6%), and anaphylaxis (4.8%). The mAbs with the highest number of adverse reaction reports were rituximab (27.6%), adalimumab (17.5%), cetuximab (11.9%), and infliximab (10.7%). CONCLUSIONS: Hypersensitivity reactions were observed more frequently than expected, although no previously unrecognized reactions were observed. Adverse reactions occurred more frequently in children and in elderly patients. Close monitoring of adverse reactions to therapeutic mAbs is therefore warranted because these can potentially cause serious medical conditions or death. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27364927 TI - H syndrome with histological features of Langerhans cell histiocytosis. PMID- 27364926 TI - miR-2861 acts as a tumor suppressor via targeting EGFR/AKT2/CCND1 pathway in cervical cancer induced by human papillomavirus virus 16 E6. AB - Persistent infection with oncogenic human papillomavirus viruses (HPVs) is a casual factor for cervical cancer and its precursors, and the abnormal constitutive expression of viral oncoprotein E6 is a key event during the malignant transformation. Here, we performed miRNA microarray to identify changes of miRNAs following ectopic HPV16 E6 overexpression in HEK293T cells and found miR-2861 was greatly decreased in both HEK293T and HaCaT cells expressing HPV16 E6 compared to vector control. Further, we demonstrated a biological link among HPV16 E6, miR-2861, EGFR, AKT2, and CCND1 in cervical cancer cells. We showed that miR-2861 was downregulated in cervical cancer tissues and negatively correlated with advanced tumor stage and lymph node metastasis. Overexpression of miR-2861 suppressed cervical cancer cell proliferation and invasion and enhanced apoptosis. Subsequent investigation revealed that EGFR, AKT2, and CCND1 were all the direct targets of miR-2861. Importantly, silencing EGFR, AKT2, and/or CCND1 recapitulated the cellular effects seen upon miR-2861 overexpression. Restoration of EGFR, AKT2, and/or CCND1 counteracted the effects of miR-2861 expression. Thus, we identified a new pathway employing miR-2861, EGFR, AKT2, and CCND1 that may mediate HPV16 E6 induced initiation and progression of cervical cancer. PMID- 27364928 TI - Subungual angioleiomyoma. PMID- 27364929 TI - Using transparent adhesive tape to prevent cross infection during contact dermoscopy. PMID- 27364930 TI - Authors' reply. PMID- 27364931 TI - Commentary on the Future of Community Psychology: Perspective of a Research Community Psychologist. AB - Community psychology is commented upon from the perspective of a community psychologist who was trained in the Community Psychology Program at the University of Michigan in Ann Arbor. Her background and training are reviewed. A brief survey of research on homelessness as a frame for community psychology research is presented. Concluding remarks are provided on the future of research in community psychology. PMID- 27364932 TI - Optimal Distribution and Utilization of Donated Human Breast Milk. AB - BACKGROUND: The nutritional content of donated expressed breast milk (DEBM) is variable. Using DEBM to provide for the energy requirements of neonates is challenging. OBJECTIVE: The authors hypothesized that a system of DEBM energy content categorization and distribution would improve energy intake from DEBM. METHODS: We compared infants' actual cumulative energy intake with projected energy intake, had they been fed using our proposed system. Eighty-five milk samples were ranked by energy content. The bottom, middle, and top tertiles were classified as red, amber, and green energy content categories, respectively. Data on 378 feeding days from 20 babies who received this milk were analyzed. Total daily intake of DEBM was calculated in mL/kg/day and similarly ranked. Infants received red energy content milk, with DEBM intake in the bottom daily volume intake tertile; amber energy content milk, with intake in the middle daily volume intake tertile; and green energy content milk when intake reached the top daily volume intake tertile. RESULTS: Actual median cumulative energy intake from DEBM was 1612 (range, 15-11 182) kcal. Using DEBM with the minimum energy content from the 3 DEBM energy content categories, median projected cumulative intake was 1670 (range 13-11 077) kcal, which was not statistically significant ( P = .418). Statistical significance was achieved using DEBM with the median and maximum energy content from each energy content category, giving median projected cumulative intakes of 1859 kcal ( P = .0006) and 2280 kcal ( P = .0001), respectively. CONCLUSION: Cumulative energy intake from DEBM can be improved by categorizing and distributing milk according to energy content. PMID- 27364933 TI - Calling rate, corticosterone plasma levels and immunocompetence of Hypsiboas albopunctatus. AB - During the breeding season, male anuran amphibians produce advertisement calls. Androgens play a permissive role in the activation of calling activity, which is often positively correlated to androgen plasma levels and testes mass. Additionally, calling effort is also correlated to corticosterone plasma levels (hereinafter referred to as CORT), which is associated with the mobilization of energy substrates to sustain the high energy flux associated with this activity. However, high CORT also has many immunosuppressive effects and might interfere with reproduction. Consequently, CORT might mediate a compromise between reproductive effort and immunocompetence in anurans. In the present study, we investigated the relationship between calling rate, immunocompetence, and CORT in Hypsiboas albopunctatus, a midsize anuran occurring in South America. To understand these relationships, we conducted focal observations of calling behavior, followed by blood collection for CORT measurements and evaluation of some immune parameters. Our results showed that individuals with larger testes had higher calling rates, and those with higher calling rates showed lower cell mediated immune response (swelling response to phytohaemagglutinin), although these relationships were not mediated by CORT. Furthermore, males calling early in the evening showed high CORT, and individuals with lower body condition index had higher CORT. We conclude that calling activity shows a cost in terms of cellular immune response in H. albopunctatus, but this compromise does not appear to be mediated by glucocorticoid plasma levels. PMID- 27364934 TI - Associations between active living-oriented zoning and no adult leisure-time physical activity in the U.S. AB - Nearly one-third of adults report no leisure-time physical activity (LTPA). Governmental and authoritative bodies recognize the role that community design through zoning code changes can play in enabling LTPA. This study examined the association between zoning and no adult LTPA in the U.S. This study was conducted between 2012 and 2016, with analyses occurring in 2015-2016. Zoning codes effective as of 2010 were compiled for jurisdictions located in the 495 most populous U.S. counties and were evaluated for pedestrian-oriented code reform zoning, 11 active living-oriented provisions (e.g., sidewalks, bike-pedestrian connectivity, mixed use, bike lanes) and a summated zoning scale (max=12). Individual-level LTPA data were obtained from the 2012 CDC Behavioral Risk Factor Surveillance System (BRFSS). County-aggregated, population-weighted zoning variables were constructed for linking to BRFSS. Log-log multivariate regressions (N=147,517 adults), controlling for individual and county characteristics and with robust standard errors clustered on county, were conducted to examine associations between zoning and no LTPA. Relative risks (RR) compared predicted lack of LTPA at 0% and 100% county-level population exposure to each zoning predictor. Zoning code reforms were associated with a 13% lower probability of no LTPA (RR: 0.87, 95% CI: 0.82-0.92). Except for crosswalks, all zoning provisions were associated with an 11-16% lower probability of no LTPA. Having all 12 zoning provisions was associated with a 22% lower probability of no LTPA (RR: 0.78, 95% CI: 0.72-0.83). The results suggest that active living-oriented zoning is a policy lever available to communities seeking to reduce rates of no LTPA. PMID- 27364936 TI - SPRINT: The Study Nephrologists Might Take With a Grain of Salt. AB - Patients with chronic kidney disease (CKD) experience several comorbidities, one of the most important being cardiovascular (CV) disease (CVD). For example, patients with stage IIIa/b CKD are more likely to die from CVD than to survive to reach end-stage renal disease. Management of hypertension, a major determinant of CV outcomes and progressive renal dysfunction, remains elusively controversial in the CKD population. In an effort to clarify this, the National Institutes of Health-funded Systolic Blood Pressure Intervention Trial (SPRINT) compared the traditional systolic 140 mm Hg goal with a more aggressive systolic goal of 120 mm Hg in a cohort of nondiabetic patients at elevated CV risk. SPRINT showed statistically significant reductions in combined CV events across all prespecified subgroups, including patients with CKD. However, SPRINT did not systematically include CKD patients, and the CKD data are merely offered as a convenience sampling. This directly limits external generalizability to CKD patients since only approximately 30% of SPRINT patients in the 120 mm Hg arm had CKD. SPRINT reaffirms the need for blood pressure control, especially in CKD patients, but is not a sufficient standalone guideline for nephrologists treating CKD in the community. A SPRINT-style study dedicated to the CKD population would be more appropriate if traditional CKD guidelines are to be challenged conclusively. PMID- 27364935 TI - The wMel strain of Wolbachia Reduces Transmission of Zika virus by Aedes aegypti. AB - Zika virus (ZIKV) is causing an explosive outbreak of febrile disease in the Americas. There are no effective antiviral therapies or licensed vaccines for this virus, and mosquito control strategies have not been adequate to contain the virus. A promising candidate for arbovirus control and prevention relies on the introduction of the intracellular bacterium Wolbachia into Aedes aegypti mosquitoes. This primarily has been proposed as a tool to control dengue virus (DENV) transmission; however, evidence suggests Wolbachia infections confer protection for Ae. aegypti against other arboviruses. At present, it is unknown whether or not ZIKV can infect, disseminate, and be transmitted by Wolbachia infected Ae. aegypti. Using Ae. aegypti infected with the wMel strain of Wolbachia that are being released in Medellin, Colombia, we report that these mosquitoes have reduced vector competence for ZIKV. These results support the use of Wolbachia biocontrol as a multivalent strategy against Ae. aegypti-transmitted viruses. PMID- 27364937 TI - The World Health Organization Global Health Emergency Workforce: What Role Will the United States Play? AB - During the May 2016 World Health Assembly of 194 member states, the World Health Organization (WHO) announced the process of developing and launching emergency medical teams as a critical component of the global health workforce concept. Over 64 countries have either launched or are in the development stages of vetting accredited teams, both international and national, to provide surge support to national health systems through WHO Regional Organizations and the delivery of emergency clinical care to sudden-onset disasters and outbreak affected populations. To date, the United States has not yet committed to adopting the emergency medical team concept in funding and registering an international field hospital level team. This article discusses future options available for health-related nongovernmental organizations and the required educational and training requirements for health care provider accreditation. (Disaster Med Public Health Preparedness. 2016;10:531-535). PMID- 27364938 TI - [Newborn and infant fractures secondary to traditional massage]. AB - The traditional massage of the newborn and young infant is an ancient practice in Africa and other regions. It has many benefits that are currently recognized, even in Western societies. However, it can be dangerous. We report two cases of fractures of the femur and clavicle that occurred in a 17-day-old newborn and a 1 month-old infant secondary to a traditional massage. In both cases, there was no concept of trauma or a history of osteogenesis imperfecta in the family or the presence of other fractures suggesting abuse. We concluded in a fracture caused by traditional massage in both cases. Given its many benefits as described in the literature, the traditional massage of young infants cannot be considered a harmful practice. However, it should be practiced with care to prevent the occurrence of such complications. PMID- 27364939 TI - [Fungal colonization in preterm neonates weighing less than 1500g admitted to the neonatal intensive care unit]. AB - Fungal colonization is a common occurrence in preterm neonates. Our objective was to describe the profile and characteristics of fungal colonization in preterm infants admitted to the Martinique NICU. From March 2012 to January 2013, an epidemiological prospective cohort study was conducted with 57 very low-birth weight infants. Cutaneous, rectal, gastric, respiratory, and urinary swabs were collected on admission, then every week for 4 weeks. The prevalence of fungal colonization was 68% (39/57): 46% by Malassezia species, 28% by Candida parapsilosis, 19% by C. albicans, 5% by C. glabrata, and 2% by C. guilliermondii. The colonized patients had a duration of parenteral nutrition and antibiotic therapy longer than the others (P<0.05). Nosocomial colonization (after 2 days of life) occurred in 52% of cases: Malassezia species and C. parapsilosis were the commensal skin yeasts most frequently implicated. Forty-nine percent (28/57) had suspected invasive fungal infections that received probabilistic treatment. Only one case of invasive fungal infection with C. glabrata was diagnosed. This study highlights the important role played by nosocomial transmission in the colonization of preterm newborns. Mycological surveillance cultures in the NICU are very useful for monitoring fungal ecology and can improve the prevention of fungal colonization in preterm infants at risk of invasive fungal infection. PMID- 27364941 TI - SYNTAX score-0 patients: risk stratification in nonobstructive coronary artery disease. AB - BACKGROUND: The complexity of coronary artery disease (CAD) is a predictor of cardiovascular events in patients with >50 % diameter stenosis as determined by SYNTAX score. Here, we compare the Gensini score to SYNTAX in patients with CAD as well as apply the Gensini score in patients with nonobstructive CAD (NOB-CAD), defined by <=50 % diameter stenosis, were the SYNTAX score cannot be utilized to define future risk. METHODS: The AtheroGene study enrolled 2316 patients [861/37.2 % with acute cardiovascular syndrome (ACS) and 1500/62.8 % with stable CAD (SCAD)]. Of these, 1966 had obstructive CAD (OB-CAD) with SYNTAX and Gensini scores available and 291 events with either cardiovascular mortality or non-fatal myocardial infarction were recorded. Furthermore, 350 patients had NOB-CAD with only Gensini score and 36 events. Median follow-up time was 4.9 years. RESULTS: In the OB-CAD cohort the SYNTAX and the Gensini score predicted outcome. Kaplan Meier curve analysis with the dichotomized Gensini score showed a significant result (p = 0.04) in the NOB-CAD cohort. Cox Regression analysis after adjustment showed a hazard ratio (HR) of 1.33 and p = 0.04 for the Gensini score in the NOB CAD cohort. Receiver operating characteristic curve (ROC) analysis provided the highest area under the curve (AUC) regarding the outcome for the Gensini score with 0.65 (p = 0.004). Comparing the SYNTAX and Gensini score in this cohort showed improved discrimination of patients with events by the Gensini score (p = 0.02). CONCLUSION: The Gensini score predicted events in patients with <=50 % diameter lesions. Utilization of this score is useful to define risk in NOB-CAD patients. PMID- 27364942 TI - Cefotaxime-induced drug rash with eosinophilia and systemic symptoms syndrome in a 7-year-old boy. PMID- 27364940 TI - Renal denervation for treatment of ventricular arrhythmias: data from an International Multicenter Registry. AB - INTRODUCTION: Ventricular arrhythmias (VAs) in patients with chronic heart failure (CHF) are sometimes refractory to antiarrhythmic drugs and cardiac ablation. This study aimed to investigate catheter-based renal sympathetic denervation (RDN) as antiarrhythmic strategy in refractory VA. METHODS: These are the first data from a pooled analysis of 13 cases from five large international centers (age 59.2 +/- 14.4 years, all male) with CHF (ejection fraction 25.8 +/- 10.1 %, NYHA class 2.6 +/- 1) presented with refractory VA who underwent RDN. Ventricular arrhythmias, ICD therapies, clinical status, and blood pressure (BP) were evaluated before and 1-12 months after RDN. RESULTS: Within 4 weeks prior RDN, a median of 21 (interquartile range 10-30) ventricular tachycardia (VT) or fibrillation (VF) episodes occurred despite antiarrhythmic drugs and prior cardiac ablation. RDN was performed bilaterally with a total number of 12.5 +/- 3.5 ablations and without peri-procedural complications. One and 3 months after RDN, VT/VF episodes were reduced to 2 (0-7) (p = 0.004) and 0 (p = 0.006), respectively. Four (31 %) and 11 (85 %) patients of these 13 patients were free from VA at 1 and 3 months. Although BP was low at baseline (116 +/- 18/73 +/- 13 mmHg), no significant changes of BP or NYHA class were observed after RDN. During follow-up, three patients died from non-rhythm-related causes. CONCLUSIONS: In patients with CHF and refractory VA, RDN appears to be safe concerning peri procedural complications and blood pressure changes, and is associated with a reduced arrhythmic burden. PMID- 27364943 TI - Thyroid hormones and complement parameters in hereditary angioedema with C1 inhibitor deficiency. AB - BACKGROUND: Thyroid hormones control and up-regulate the synthesis of many plasma proteins. OBJECTIVE: To explore possible associations between thyroid hormone and complement levels in patients with hereditary angioedema resulting from the deficiency of the C1-inhibitor (C1-INH-HAE). METHODS: In this case-control study, serum thyrotropin, free triiodothyronine (FT3), and free thyroxine (FT4) levels, anti-thyroid peroxidase and antithyroglobulin antibody titers, and C1-INH concentrations were measured in 117 euthyroid patients with C1-INH-HAE and compared with their clinical properties. The control group comprised 150 healthy, age- and sex-matched, euthyroid individuals. RESULTS: The thyrotropin and antithyroglobulin levels were similar between the patients and the controls. Significantly lower FT3 (P < .001) and FT4 (P = .002) levels, as well as higher anti-thyroid peroxidase titers (P < .001), were seen in the patients with C1-INH HAE. The proportion of patients with reduced C1-INH activity was greater among those with below-median FT4 levels than among those with above-median values (P = .02). Patients who experienced more edematous attacks per year had lower FT4 levels (within the normal range) than those afflicted by fewer episodes (P = .01). The FT3 and FT4 levels were significantly higher in patients undergoing long-term danazol therapy than in those who did not receive this drug (P = .01 and P = .02, respectively). The proportion of patients with FT4 levels in the below-median range was higher in the subset with increased d-dimer concentration (P = .009). CONCLUSION: Minor variations of the thyroid hormone levels (within the reference range) can influence the function of C1-INH in C1-INH-HAE. Our findings suggest a role for the endocrine system in the pathophysiology of C1-INH HAE. PMID- 27364945 TI - Discussion. PMID- 27364944 TI - Postoperative autotransfusion drain after total hip arthroplasty: a meta-analysis of randomized controlled trials. AB - The use of a postoperative autotransfusion drain (PATD) to reduce allogenic blood transfusions in total hip arthroplasty (THA) remains controversial. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of this technique. Randomized controlled trials (RCTs) were identified from PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL). Thirteen RCTs (1,424 participants) were included in our meta-analysis. The results showed that PATD reduced the rate of allogenic transfusions (RR = 0.56; 95% CI [0.40, 0.77]) and total blood loss (MD = -196.04; 95% CI [-311.01, -81.07]). Haemoglobin (Hb) levels were higher in the PATD group on postoperative day 1 (MD = 0.28; 95% CI [0.06, 0.49]), but no significant differences on postoperative days 2 or 3 (MD = 0.29; 95% CI [-0.02, 0.60]; MD = 0.26; 95% CI [-0.04, 0.56]; respectively). There were no differences in length of hospital stay (MD = -0.18; 95% CI [-0.61, 0.25]), febrile reaction (RR = 1.26; 95% CI [0.95, 1.67]), infection (RR = 0.95; 95% CI [0.54, 1.65]), wound problems (RR = 1.07; 95% CI [0.87, 1.33]), or serious adverse events (RR = 0.59; 95% CI [0.10, 3.58]). Our findings suggest that PATD is effective in reducing the rate of allogenic transfusion. However, the included studies are inadequately powered to conclusively determine the safety of this technique. PMID- 27364946 TI - Abdominal aortic aneurysm repair in octogenarians is associated with higher mortality compared with nonoctogenarians. AB - OBJECTIVE: Age is a well-known independent risk factor for death after abdominal aortic aneurysm (AAA) repair. However, there is significant debate about the utility of AAA repair in older patients. In this study, mortality outcomes after endovascular AAA repair (EVAR) and open AAA repair (OAR) in octogenarians (aged >=80 years) were compared with younger patients (aged <80 years). METHODS: All patients recorded in the Vascular Quality Initiative database (2002-2012) who underwent infrarenal AAA repair were included. Univariable and multivariable statistics were used to compare perioperative (30-day) and 1-year mortality outcomes between octogenarians vs nonoctogenarians for OAR and EVAR. RESULTS: During the study period, 21,874 patients underwent AAA repair (OAR, 5765; EVAR, 16,109), including 4839 octogenarians (OAR, 765; EVAR, 4074) and 17,035 nonoctogenarians (OAR, 5000; EVAR, 12,035). Octogenarians (mean age, 83.0 +/- 0.1 years) were less frequently male (66% vs 75%) and had a higher prevalence of congestive heart failure (9.9% vs 7.1%), chronic renal insufficiency (12.2% vs 7.5%), and a history of aortic surgery (14.3% vs 7.7%) compared with nonoctogenarians (P < .01 for all). Intraoperative use of blood transfusions and vasopressors was more common in octogenarians for OAR (blood: 3.3 +/- 4.4 vs 1.8 +/- 3.7 units; vasopressors: 45.2% vs 32.8%) and EVAR (blood: 0.43 +/- 1.7 vs 0.31 +/- 1.6 units; vasopressors: 7.6% vs 5.7%; P < .01 for all). Contrast dye volumes used during EVAR were similar in octogenarians and nonoctogenarians (108 +/- 71 vs 107 +/- 68 mL; P = .18). Perioperative mortality after OAR was 20.1% in octogenarians compared with 7.1% in nonoctogenarians (P < .01). Perioperative mortality after EVAR was 3.8% in the octogenarians compared with 1.6% in nonoctogenarians (P < .01). One-year mortality among octogenarians vs nonoctogenarians was 26% vs 9.7% for OAR and 8.9% vs 4.3% for EVAR (log-rank test, P < .01 for both). Multivariable analysis controlling for baseline and intraoperative differences between groups demonstrated that age >=80 years increased the risk of 30-day and 1-year mortality after AAA repair by 223% and 187%, respectively (P < .01 for both). CONCLUSIONS: AAA repair should be approached with extreme caution in octogenarians. Perioperative and 1-year mortality rates after OAR are particularly high in the older population, suggesting that the appropriate aneurysm size threshold for OAR might be larger due to the greater operative risk in octogenarian patients. PMID- 27364948 TI - Gut Inflammation in Mice Triggers Proliferation and Function of Mucosal Foxp3+ Regulatory T Cells but Impairs Their Conversion from CD4+ T Cells. AB - BACKGROUND AND AIMS: Regulatory Foxp3+CD4+ T cells [Tregs] have been implicated in the control of colitis in T-cell transfer models, yet their ability to regulate colitis induced by innate immunity and the impact of gut inflammation on their fate and function have been poorly documented. METHODS: Colitis was induced by dextran sodium sulphate in DEREG transgenic mice. Tregs ablation and transfer experiments showd that Tregs could limit the severity of colitis in B6 mice. RESULTS: Gut inflammation resulted in increased number of Tregs in mesenteric lymph nodes [MLN] and colon lamina propria [LP], although their frequency decreased due to massive concomitant leukocyte infiltration. This coincided at both sites with a dramatic increase in Ki67+ Tregs which retained proliferative capacity. Gut inflammation resulted in enhanced suppressive function of Tregs in colon lamina propria and neuropillin-1- [NRP1-] Treg in MLN. Real-time polymerase chain reaction analysis and flow cytometry [using IL10-egfp-reporter mice] showed that compared with NRP1+ Treg, NRP1- Treg express higher levels of IL-10 transcripts and were enriched in IL10-expressing cells both in the steady state and during colitis. Moreover, Treg conversion in vivo from from naive CD4+ T cells or Treg precursors was impaired in colitic mice. Finally, gut inflammation caused a decrease in intestinal dendritic cells, affecting both CD103+CD11b+ and CD103+CD11b- subsets and affected their Treg conversion capacity. CONCLUSIONS: Together, our data indicate that non-specific colon inflammation triggers proliferation and suppressive function of Tregs in the lamina propria and MLN, but impairs their de novo conversion from CD4+ T cells by intestinal dendritic cells. PMID- 27364947 TI - Slug inhibits pancreatic cancer initiation by blocking Kras-induced acinar-ductal metaplasia. AB - Cells in the pancreas that have undergone acinar-ductal metaplasia (ADM) can transform into premalignant cells that can eventually become cancerous. Although the epithelial-mesenchymal transition regulator Snail (Snai1) can cooperate with Kras in acinar cells to enhance ADM development, the contribution of Snail related protein Slug (Snai2) to ADM development is not known. Thus, transgenic mice expressing Slug and Kras in acinar cells were generated. Surprisingly, Slug attenuated Kras-induced ADM development, ERK1/2 phosphorylation and proliferation. Co-expression of Slug with Kras also attenuated chronic pancreatitis-induced changes in ADM development and fibrosis. In addition, Slug attenuated TGF-alpha-induced acinar cell metaplasia to ductal structures and TGF alpha-induced expression of ductal markers in ex vivo acinar explant cultures. Significantly, blocking the Rho-associated protein kinase ROCK1/2 in the ex vivo cultures induced expression of ductal markers and reversed the effects of Slug by inducing ductal structures. In addition, blocking ROCK1/2 activity in Slug expressing Kras mice reversed the inhibitory effects of Slug on ADM, ERK1/2 phosphorylation, proliferation and fibrosis. Overall, these results increase our understanding of the role of Slug in ADM, an early event that can eventually lead to pancreatic cancer development. PMID- 27364949 TI - Smooth Muscle Hyperplasia/Hypertrophy is the Most Prominent Histological Change in Crohn's Fibrostenosing Bowel Strictures: A Semiquantitative Analysis by Using a Novel Histological Grading Scheme. AB - BACKGROUND: The simplistically and ambiguously termed 'fibrostenosis' of bowel is a hallmark of severe Crohn's disease [CD] and a major contributor to medical treatment failure. Non-invasive imaging assessment and novel medical therapy targeting this condition are under investigation, which particularly requires a better understanding of the underlying histological basis. METHODS: We analysed 48 patients with stricturing Crohn's ileitis or/and colitis that required surgical resection. The most representative sections of the fibrostenotic, non stenotic and uninvolved regions were reviewed for histological analysis. For each layer of bowel wall (mucosa including muscularis mucosae [MU], submucosa [SM], muscularis propria [MP], subserosal adventitia [SS]), histological abnormalities were evaluated individually, including active and chronic inflammation, fibrosis, smooth muscle hyperplasia or hypertrophy, neuronal hypertrophy and adipocyte proliferation. A novel semiquantitative histological grading scheme was created. RESULTS: The most significant histopathological features characterizing the stricturing intestines were smooth muscle hyperplasia of SM, hypertrophy of MP and chronic inflammation. The muscular alteration was predominant in all layers. The overall muscular hyperplasia/hypertrophy was positively correlated with chronic inflammation and negatively correlated with fibrosis, whereas SM muscular hyperplasia was also associated with MU active inflammation. Similar changes, to a lesser extent, occurred in the adjacent non-stenotic inflamed bowel as well. CONCLUSIONS: In CD-associated 'fibrostenosis', it is the smooth muscle hyperplasia/hypertrophy that contributes most to the stricturing phenotype, whereas fibrosis is less significant. The 'inflammation-smooth muscle hyperplasia axis' may be the most important in the pathogenesis of Crohn's strictures. PMID- 27364950 TI - Heparin exerts anti-apoptotic effects on uterine explants by targeting the endocannabinoid system. AB - Miscarriage caused by Gram-negative bacteria infecting the female genital tract is one of the most common complications of human pregnancy. Intraperitoneal administration of LPS to 7-days pregnant mice induces embryo resorption after 24 h. Here, we show that LPS induced apoptosis on uterine explants from 7-days pregnant mice and that CB1 receptor was involved in this effect. On the other hand, heparin has been widely used for the prevention of pregnancy loss in women with frequent miscarriage with or without thrombophilia. Besides its anticoagulant properties, heparin exerts anti-inflammatory, immunomodulatory and anti-apoptotic effects. Here, we sought to investigate whether the administration of heparin prevented LPS-induced apoptosis in uterine explants from 7-days pregnant mice. We found that heparin enhanced cell survival in LPS-treated uterine explants and that this effect was mediated by increasing uterine FAAH activity. Taken together, our results point towards a novel mechanism involved in the protective effects of heparin. PMID- 27364951 TI - Vitamin E synthetic derivate-TPGS-selectively induces apoptosis in jurkat t cells via oxidative stress signaling pathways: implications for acute lymphoblastic leukemia. AB - D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) is a water-soluble derivative of natural vitamin E commonly used as a drug delivery agent. Recently, TPGS alone has been reported to induce cell death in lung, breast and prostate cancer. However, the effect of TPGS on cancer cell viability remains unclear. Thus, this study was aimed to evaluate the cytotoxic effect of TPGS on human periphral blood lymphocytes (PBL) and on T cell acute lymphocytic leukemia (ALL) Jurkat clone E6-1 cells and its possible mechanism of action. PBL and Jurkat cells were treated with TPGS (10, 20, 40, 60, and 80 MUM), and morphological changes in the cell nucleus, mitochondrial membrane potential (DeltaPsim), and intracellular reactive oxygen species levels were determined by immune fluorescence microscopy and flow cytometry. Cellular apoptosis markers were also evaluated by immunocytochemistry. In this study, TPGS induced apoptotic cell death in Jurkat cells, but not in PBL, in a dose-response manner with increasing nuclear DNA fragmentation, increasing cell cycle arrest, and decreasing DeltaPsim. Additionally, TPGS increased dichlorofluorescein fluorescence intensity, indicative of H2O2 production, in a dose-independent fashion. TPGS increased DJ-1 Cys(106)-sulfonate, as a marker of intracellular stress and induced the activation of NF-kappaB, p53 and c-Jun transcription factors. Additionally, it increased the expression of apoptotic markers Bcl-2 related pro apoptotic proteins Bax and PUMAand activated caspase-3. The antioxidant N-acetyl L-cysteine and known pharmacological inhibitors protected the cells from the TPGS induced effects. In conclusion, TPGS selectively induces apoptosis in Jurkat cells through two independent but complementary H2O2-mediated signaling pathways. Our findings support the use of TPGS as a potential treatment for ALL. PMID- 27364952 TI - Dihydroceramide-desaturase-1-mediated caspase 9 activation through ceramide plays a pivotal role in palmitic acid-induced HepG2 cell apoptosis. AB - In this study, results showed that the inhibition of PA-induced HepG2 cell growth takes place in a time- and concentration-dependent manner, that activation of caspase 9 is necessary for PA-induced HepG2 cell apoptosis, that dihydroceramide desaturase 1 (DES1) plays a key role in PA-mediated caspase 9 and caspase 3 activation, and that palmitoleic acid (POA), an omega-7 monounsaturated fatty acid, reverses PA-induced apoptosis through DES1 -> Ceramide -> Caspase 9 -> Caspase 3 signaling. PMID- 27364954 TI - Age at Death in Individuals with Intellectual Disabilities. AB - BACKGROUND: We aimed to ascertain the average age at death (AD) in the intellectual disability population for each gender and compare them to those of the general population during 1970-2012. METHODS: By analysing medical records, we calculated the ADs of all deceased clients (N = 1236) of two district organizations responsible for intellectual disability services. Statistics Finland's database generated data regarding ADs of all inhabitants who had died after having resided in same district. RESULTS: During the follow-up, average ADs for the intellectual disability population and general population increased, and simultaneously the AD difference between these populations decreased. In the 2000s, the AD difference between the intellectual disability population and the whole population was 22 years for men (95% CI: -24 to -20) and 30 years for women (95% CI: -33 to -27). In 2000s, the mean AD of those with mild-to-moderate intellectual disability (IQ 50-69) for women and men was 56 (SD17) and 54 (SD18), and those with severe to profound intellectual disability (IQ<50), 44 (SD23) and 43 (SD21). CONCLUSIONS: Intellectual disability is still a considerable risk factor for early death. Among the intellectual disability population, unlike in general population, the lifespans of women and men are equal. PMID- 27364953 TI - Partial inactivation of GABAA receptors containing the alpha5 subunit affects the development of adult-born dentate gyrus granule cells. AB - Alterations of neuronal activity due to changes in GABAA receptors (GABAA R) mediating tonic inhibition influence different hippocampal functions. Gabra5-null mice and alpha5 subunit((H105R)) knock-in mice exhibit signs of hippocampal dysfunction, but are capable of improved performance in several learning and memory tasks. Accordingly, alleviating abnormal GABAergic tonic inhibition in the hippocampal formation by selective alpha5-GABAA R modulators represents a possible therapeutic approach for several intellectual deficit disorders. Adult neurogenesis in the dentate gyrus is an important facet of hippocampal plasticity; it is regulated by tonic GABAergic transmission, as shown by deficits in proliferation, migration and dendritic development of adult-born neurons in Gabra4-null mice. Here, we investigated the contribution of alpha5-GABAA Rs to granule cell development, using retroviral vectors expressing eGFP for labeling precursor cells in the subgranular zone. Global alpha5-GABAA R knockout (alpha5 KO) mice showed no alterations in migration and morphological development of eGFP positive granule cells. However, upregulation of alpha1 subunit-immunoreactivity was observed in the hippocampal formation and cerebral cortex. In contrast, partial gene inactivation in alpha5-heterozygous (alpha5-het) mice, as well as single-cell deletion of Gabra5 in newborn granule cells from alpha5-floxed mice, caused severe alterations of migration and dendrite development. In alpha5-het mice, retrovirally mediated overexpression of Cdk5 resulted in normal migration and dendritic branching, suggesting that Cdk5 cooperates with alpha5-GABAA Rs to regulate neuronal development. These results show that minor imbalance of alpha5 GABAA R-mediated transmission may have major consequences for neuronal plasticity; and call for caution upon chronic therapeutic use of negative allosteric modulators acting at these receptors. PMID- 27364955 TI - Dose-Dependent Effect of Piragliatin, a Glucokinase Activator, on the QT Interval Following Short-Term Multiple Doses in Patients With Type 2 Diabetes Mellitus. AB - To determine the effect of piragliatin on the QTcS (QT-corrected study-specific) interval, a double-blind, double-dummy, placebo-controlled, active-comparator, 4 period, 4-treatment, 4-sequence randomized crossover trial was performed in 42 patients with type 2 diabetes mellitus who received 100 and 200 mg piragliatin twice daily, placebo, and 400 mg moxifloxacin (on day 1 and day 5 only) for 5 days. In the categorical analyses, piragliatin did not have a clinically significant effect on the QTcS interval at either dose, and the majority of patients were categorized with low risk for maximum change from baseline (<=30 milliseconds) and a maximum postbaseline QTcS interval as normal (<=450 milliseconds). However, in the analysis of variance model, both piragliatin doses crossed the 10-millisecond threshold (100 mg twice daily on day 5, hour 1; 200 mg twice daily on days 1 and 5, hours 1 and 2) with P values indicating statistical significance. Headache and mild hypoglycemia were the most frequent adverse events associated with piragliatin treatment. There appeared that the effect of piragliatin treatment on the QTc interval was dose/exposure dependent following short-term multiple doses. Longer-term monitoring of electrocardiograms with pharmacokinetic exposure should continue, especially at conditions for potentially higher pharmacokinetic exposure. PMID- 27364956 TI - Contact dermatitis. PMID- 27364957 TI - molSimplify: A toolkit for automating discovery in inorganic chemistry. AB - We present an automated, open source toolkit for the first-principles screening and discovery of new inorganic molecules and intermolecular complexes. Challenges remain in the automatic generation of candidate inorganic molecule structures due to the high variability in coordination and bonding, which we overcome through a divide-and-conquer tactic that flexibly combines force-field preoptimization of organic fragments with alignment to first-principles-trained metal-ligand distances. Exploration of chemical space is enabled through random generation of ligands and intermolecular complexes from large chemical databases. We validate the generated structures with the root mean squared (RMS) gradients evaluated from density functional theory (DFT), which are around 0.02 Ha/au across a large 150 molecule test set. Comparison of molSimplify results to full optimization with the universal force field reveals that RMS DFT gradients are improved by 40%. Seamless generation of input files, preparation and execution of electronic structure calculations, and post-processing for each generated structure aids interpretation of underlying chemical and energetic trends. (c) 2016 Wiley Periodicals, Inc. PMID- 27364958 TI - Protein effects in non-heme iron enzyme catalysis: insights from multiscale models. AB - Many non-heme iron enzymes have similar sets of ligands but still catalyze widely different reactions. A key question is, therefore, the role of the protein in controlling reactivity and selectivity. Examples from multiscale simulations, primarily QM/MM, of both mono- and binuclear non-heme iron enzymes are used to analyze the stability of these models and what they reveal about the protein effects. Consistent results from QM/MM modeling are the importance of the hydrogen bond network to control reactivity and electrostatic stabilization of electron transfer from second-sphere residues. The long-range electrostatic effects on reaction barriers are small for many systems. In the systems where large electrostatic effects have been reported, these lead to higher barriers. There is thus no evidence of any significant long-range electrostatic effects contributing to the catalytic efficiency of non-heme iron enzymes. However, the correct evaluation of electrostatic contributions is challenging, and the correlation between calculated residue contributions and the effects of mutation experiments is not very strong. The largest benefits of QM/MM models are thus the improved active-site geometries, rather than the calculation of accurate energies. Reported differences in mechanistic predictions between QM and QM/MM models can be explained by differences in hydrogen bonding patterns in and around the active site. Correctly constructed cluster models can give results with similar accuracy as those from multiscale models, but the latter reduces the risk of drawing the wrong mechanistic conclusions based on incorrect geometries and are preferable for all types of modeling, even when using very large QM parts. PMID- 27364959 TI - The mechanisms of sudden-onset type adverse reactions to oseltamivir. AB - Oseltamivir is contraindicated for people aged 10-19 in principle in Japan, due to concern about abnormal behaviours. Sudden death is another concern. This review examines growing evidence of their association and discusses underlying mechanisms of these sudden-onset type reactions to oseltamivir. First, the importance of animal models and the concept of human equivalent dose (HED) is summarized. Second, the specific condition for oseltamivir use, influenza infection, is reviewed. Third, findings from toxicity studies conducted prior to and after the marketing of oseltamivir are reported on to provide context on the observation of a possible causal association. Fourth, similarity and consistency of toxicity in humans with that in other animals is described. Finally, coherence of toxicokinetic and molecular level of evidence (channels, receptors and enzymes), including differences from the toxicity of other neuraminidase inhibitors, is reviewed. It is concluded that unchanged oseltamivir has various effects on the central nervous system (CNS) that may be related to clinical findings including hypothermia, abnormal behaviours including with fatal outcome, and sudden death. Among receptors and enzymes related to CNS action, it is known that oseltamivir inhibits nicotinic acetylcholine receptors, which are closely related to hypothermia, as well as human monoamine oxidase-A (MAO-A), which is closely related to abnormal or excitatory behaviours. Receptors such as GABAA , GABAB and NMDA and their related receptors/channels including Na+ and Ca2+ channels are thought to be other candidates for investigation related to respiratory suppression followed by sudden death and psychotic reactions (both acute and chronic), respectively. PMID- 27364960 TI - What Scales the T Cell Response? AB - T cells are known to scale their clonal expansion and effector cytokine response according to the dose and strength of antigenic signal so as to balance their role of affecting protection with the intertwined and immunologically driven tissue damage. How T cells achieve this is now beginning to be understood. We underscore temporal integration of digital T cell receptor (TCR) signaling as the basis for achieving scaled response by means of accumulating crucial mediators over time. We also discuss the role of temporally integrated crosstalk between TCR and IL2 signaling in mediating a scaled, coherent, collective response by T cells. Finally, we highlight numerous known and putative regulatory interactions in the transcriptional program that are expected to quantitatively scale the T cell response, and also offer new mechanisms to hitherto unexplained observations. PMID- 27364961 TI - Depression-Like Adult Behaviors may be a Long-Term Result of Experimental Pneumococcal Meningitis in Wistar Rats Infants. AB - Pneumococcal meningitis is a life-threatening infection of the central nervous system (CNS) with a high mortality rate. In addition to causing severe neurological sequelae infectious diseases of the CNS can play a significant role in the pathogenesis of neuropsychiatric disorders. In this study infant Wistar rats, postnatal day 11, received intracerebroventricular (i.c.v.) either artificial cerebrospinal fluid (CSF) or a Streptococcus pneumoniae suspension to a concentration of 1 * 106 colony-forming units (CFU). 18 h later animals received antibiotic treatment as usual during 7 days. On postnatal day 46, the animals received imipramine intraperitoneal (i.p.) or sterile NaCl during 14 days (postnatal days 46-60). Then, on postnatal days 59-60 we evaluated the consumption of sweet food (an index of anhedonia). On postnatal day 60 the animals were submitted to the forced swimming task. 60 min after this task the animals were decapitated and the blood was collected to evaluate adrenocorticotropic hormone (ACTH) and corticosterone. Immediately after blood collection the hippocampus was removed to evaluate brain-derived neurotropic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). The meningitis group exhibited depressive-like behavior as evidenced by decreased sucrose intake and increased immobility time in the forced swimming task, and BDNF and GDNF decrease in the hippocampus. ACTH levels were increased in the blood. Imipramine treatment reversed depressive-like behaviors, re-established hippocampal BDNF and GDNF expression, and normalized ACTH levels in the blood. Here we demonstrate that meningitis during early life period can trigger depressive-like behavior in adult life of rats. PMID- 27364962 TI - Epigallocatechin Gallate (EGCG) Inhibits Alpha-Synuclein Aggregation: A Potential Agent for Parkinson's Disease. AB - Protein aggregation is a prominent feature of many neurodegenerative disorders including Parkinson's disease (PD). Aggregation of alpha-synuclein (SNCA) may underlie the pathology of PD. They are the main components of Lewy bodies and dystrophic neurites that are the intraneuronal inclusions characteristic of the disease. We have demonstrated that the polyphenol (-)-epi-gallocatechine gallate (EGCG) inhibited SNCA aggregation, which made it a candidate for therapeutic intervention in PD. Three methods were used: SNCA fibril formation inhibition by EGCG in incubates; inhibition of the SNCA fluorophore A-Syn-HiLyte488 binding to plated SNCA in microwells; and inhibition of the A-Syn-HiLyte488 probe binding to aggregated SNCA in postmortem PD tissue. Recombinant human SNCA was incubated under conditions that result in fibril formation. The aggregation was blocked by 100 nM EGCG in a concentration-dependent manner, as shown by an absence of thioflavin T binding. In the microplate assay system, the ED50 of EGCG inhibition of A-Syn-HiLyte488 binding to coated SNCA was 250 nM. In the PD tissue based assay, SNCA aggregates were recognized by incubation with 7 nM of A-Syn HiLyte488. This binding was blocked by EGCG in a concentration dependent manner. The SNCA amino acid sites, which potentially interacted with EGCG, were detected on peptide membranes. It was implicated that EGCG binds to SNCA by instable hydrophobic interactions. In this study, we suggested that EGCG could be a potent remodeling agent of SNCA aggregates and a potential disease modifying drug for the treatment of PD and other alpha-synucleinopathies. PMID- 27364963 TI - Neuronal expression of c-Fos after epicortical and intracortical electric stimulation of the primary visual cortex. AB - Electrical stimulation of the primary visual cortex (V1) is an experimental approach for visual prostheses. We here compared the response to intracortical and epicortical stimulation of the primary visual cortex by using c-Fos immunoreactivity as a marker for neuronal activation. The primary visual cortex of male Sprague Dawley rats was unilaterally stimulated for four hours using bipolar electrodes placed either intracortically in layer IV (n=26) or epicortically (n=20). Four different current intensities with a constant pulse width of 200MUs and a constant frequency of 10Hz were used, for intracortical stimulation with an intensity of 0MUA (sham-stimulation), 10MUA, 20MUA and 40MUA, and for epicortical stimulation 0MUA, 400MUA, 600MUA and 800MUA. Subsequently all animals underwent c-Fos immunostaining and c-Fos expression was assessed in layer I-VI of the primary visual cortex within 200MUm and 400MUm distance to the stimulation site. C-Fos expression was higher after intracortical stimulation compared to epicortical stimulation, even though ten times lower current intensities were applied. Furthermore intracortical stimulation resulted in more focal neuronal activation than epicortical stimulation. C-Fos expression was highest after intracortical stimulation with 20MUA compared to all other intensities. Epicortical stimulation showed a linear increase of c-Fos expression with the highest expression at 800MUA. Sham stimulation showed similar expression of c-Fos in both hemispheres. The contralateral hemisphere was not affected by intracortical or epicortical stimulation of either intensities. In summary, intracortical stimulation resulted in more focal neuronal activation with less current than epicortical stimulation. This model may be used as a simple but reliable model to evaluate electrodes for microstimulation of the primary visual cortex before testing in more complex settings. PMID- 27364964 TI - Reproducibility of low-dose stereography measurements of femoral torsion after IM nailing of femoral shaft fractures and in intact femurs. AB - INTRODUCTION: Rotational malunion is a complication of intramedullary (IM) nailing for femur fractures. Symptoms can appear with 15 degrees or more of axial deformity. None of the currently available measurement methods have a satisfactory reliability/irradiation ratio. The purpose of this study was to study the reproducibility of measuring femoral torsion with an EOS((r)) low-dose stereography (LDX) system. HYPOTHESIS: LDX is a reproducible method for measuring post-traumatic femoral torsion. MATERIAL AND METHODS: The intra- and inter observer reproducibility was studied in 45 patients who had a femoral fracture treated by IM nailing. Both the injured and contralateral healthy femurs were modelled. Bland-Altman plots were used to analyze the measurements made by three different observers (two orthopedic surgeons and one radiologist). For a given comparison, the interval between the upper limit of agreement (ULA) and lower limit of agreement (LLA) had to be within [-5 degrees ; 5 degrees ] for the examination to qualify as reproducible. Measurements were made by three observers (A, B, C) on the injured and healthy femur. RESULTS: With the fractured femurs (n=39), the intra-observer [LLA; ULA] interval was [-16.295; 12.977]; it was [ 18.475; 16.744] for the A-B pairing, [-13.316; 13.532] for the B-C pairing and [ 17.839; 19.355] for the A-C pairing. With the healthy femurs (n=37), the intra observer [LLA; ULA] interval was [-7.909; 7.88]; it was [-11.924; 11.639] for the A-B pairing, [-12.654; 11.93] for the B-C pairing and [-11; 12.009] for the A-C pairing. DISCUSSION: The [LLA; ULA] intervals were greater than the [-5; +5] interval in all cases. LDX reproducibility is not sufficient for measuring femoral torsion after fracture or in healthy femurs. Observer experience, cohort size and the perfectible image quality are likely sources of bias. Conversely, the use of Bland-Altman plots and the multidisciplinary training of observers are major strengths of this study. Reproducibility will likely improve as the software is developed further and the image acquisition improves. PMID- 27364965 TI - Mid-term survivorship of Mini-keelTM versus Standard keel in total knee replacements: Differences in the rate of revision for aseptic loosening. AB - INTRODUCTION: To reduce the size of the surgical incision, modular mini-keel tibial components have been developed with or without extensions for the NexgenTM MIS Tibial Component. Although a smaller component could theoretically result in defective fixation, this has never been evaluated in a large comparative series. Thus, we performed the following case control study to: (1) evaluate intermediate term survival of a modular "mini-keel" tibial component compared to a reference standard keel component from the same line of products (Nexgen LPS-Flex Tibial Component, Zimmer); (2) to identify any eventual associated factors if the frequency of loosening was increased. HYPOTHESIS: The rate of revision for aseptic tibial loosening is comparable for both components. MATERIALS AND METHODS: This comparative, retrospective, single center series of 459 consecutive total knee arthroplasties (TKA) was performed between 2007 and 2010: with 212 modular "mini-keel" (MK) tibial components and 247 "standard" (S) components. Survival, rate of revision for aseptic tibial loosening and identification of a radiolucent line were analyzed at the final follow-up. RESULTS: After a median follow-up of 5years, the rate of revision for tibial aseptic loosing was significantly higher in the MK group with 12 cases (5.7%) and 4 cases in the S group (1.6%) (P=0.036). The use of the MK component appears to be a prognostic factor for surgical revision (hazard ratio=3.86 (1.23-11.88), P=0.02) but not for the development of a radiolucent line (HR=1.75 (0.9-3.4), P=0.097). The mean delay before revision was 38months (8-64) in the MK group and 15.2months (8-22) in the S group (P=0.006). Individual factors, such as gender, body mass index (BMI) and pre- or postoperative alignment were not prognostic factors for revision or radiolucent lines. CONCLUSION: The modular "mini-keel" tibial component was associated with a greater risk of revision for tibial component loosening. LEVEL OF EVIDENCE: Case control study, III. PMID- 27364966 TI - Mid-term results of arthroscopic Bankart repair: A review of 31 cases. AB - INTRODUCTION: The goal of this study was to assess the overall function (Walch Duplay score), stability, time and because it is time of return to sport and level of return to sport, and satisfaction of patients who underwent an arthroscopic Bankart repair for chronic anterior shoulder instability at 5 years' follow-up. In addition, the potential correlation between the postoperative Walch Duplay score and the presence of risk factors for recurrence, the ISIS score, associated labral lesions discovered intraoperatively and clinical presentation was determined. MATERIAL AND METHODS: This was a retrospective, single-centre study of 30 patients (31 arthroscopic Bankart procedures) operated between January 2003 and December 2012. The Walch-Duplay score, recurrence rate (dislocation or subluxation), return to sports and subjective satisfaction were evaluated. RESULTS: The mean postoperative Duplay score was 77.4 points (100 15)+/-30.6. At review, 25.8% of patients had recurrence of the preoperative symptoms, including 16.1% glenohumeral dislocation and 9.7% subluxation. Patients requiring revision surgery (Bristow-Latarjet procedure) had no additional instability episodes. Among the athletes, 16 (66.6%) returned to their pre-injury level, four (16.6%) changed to a different sport and four stopped participating (16.6%). The subjective evaluation of the procedure was satisfactory in 75% of cases. No risk factors for recurrence were significantly related to the Walch Duplay score. CONCLUSION: Despite satisfactory Walch-Duplay scores and subjective results, this mid-term follow-up study revealed a significant number of patients with recurrent instability after arthroscopic Bankart repair, confirming published data. Careful patient selection is essential prior to proposing this procedure and patients should be informed of the potential risk of revision surgery. LEVEL OF EVIDENCE: Level IV, retrospective study. PMID- 27364967 TI - Nutritional Assessment. AB - Nutritional assessment focuses on evaluation of animal-specific, diet-specific, feeding management, and environmental factors. Assessment includes evaluation of a patient's medical history, comprehensive diet history, and physical examination including body weight, body condition, and muscle condition. Diagnostic testing may identify comorbidities associated with obesity or concurrent health conditions that need to be considered when developing a nutrition plan. When obesity is diagnosed during the nutritional assessment this finding along with health implications must be clearly communicated to the pet owner. Careful consideration of animal-specific, diet-specific, owner-specific, and environmental factors allows the clinician to develop a specific nutrition plan tailored to the needs of pet and owner. PMID- 27364968 TI - Decongestion in Acute Heart Failure: Does the End Justify the Means? PMID- 27364969 TI - The Year in Heart Failure Review 2015 to 2016. PMID- 27364970 TI - BMI Is a Potential Confounder of Postpartum Relaxin-2 and Short-Term Left Ventricular Function Following Peripartum Cardiomyopathy. PMID- 27364971 TI - Reply: BMI Is a Potential Confounder of Post-Partum Relaxin-2 and Short-Term Left Ventricular Function Following Peripartum Cardiomyopathy. PMID- 27364972 TI - Medicare Trends of Takotsubo Cardiomyopathy Outcomes: Is it Just the Tip of an Iceberg? PMID- 27364973 TI - Hafnia (HfO2) nanoparticles as an X-ray contrast agent and mid-infrared biosensor. AB - The interaction of hafnium oxide (HfO2) nanoparticles (NPs) with X-ray and mid infrared radiation was investigated to assess the potential as a multifunctional diagnostic probe for X-ray computed tomography (CT) and/or mid-infrared biosensing. HfO2 NPs of controlled size were prepared by a sol-gel process and surface functionalized with polyvinylpyrrolidone, resulting in relatively spherical and monodispersed NPs with a tunable mean diameter in the range of ~7 31 nm. The X-ray attenuation of HfO2 NPs was measured over 0.5-50 mM concentration and compared with Au NPs and iodine, which are the most prominent X ray contrast agents currently used in research and clinical diagnostic imaging, respectively. At clinical CT tube potentials >80 kVp, HfO2 NPs exhibited superior or similar X-ray contrast compared to Au NPs, while both exhibited significantly greater X-ray contrast compared to iodine, due to the favorable location of the k shell absorption edge for hafnium and gold. Moreover, energy-dependent differences in X-ray attenuation enabled simultaneous quantitative molecular imaging of each agent using photon-counting spectral (multi-energy) CT. HfO2 NPs also exhibited a strong mid-infrared absorption in the Reststrahlen band from ~250-800 cm(-1) and negative permittivity below 695 cm(-1), which can enable development of mid-infrared biosensors and contrast agents, leveraging surface enhanced mid-infrared and/or phonon polariton absorption. PMID- 27364974 TI - Expression of transforming growth factor beta1 promotes cholangiocarcinoma development and progression. AB - BACKGROUND AND AIMS: The role of transforming growth factor beta 1 (TGFbeta1) in cholangiocarcinoma (CCA) initiation and growth requires further definition. METHODS: We employed pharmacological and genetic approaches to inhibit or enhance TGFbeta1 signaling, respectively, and determine the cellular mechanisms involved. RESULTS: It was observed that inhibiting TGFbeta1 activity with short hairpin RNA (shRNA) or pharmaceutical agents suppressed CCA development and growth, whereas overexpression of TGFbeta1 enhanced CCA tumor size and promoted intrahepatic metastasis in a rat model. Suppression of TGFbeta1 activity inhibits downstream target gene expression mediated by miR-34a that includes cyclin D1, CDK6, and c Met. In addition, "knockdown" of TGFbeta1 expression revealed a miR-34a positive feedback mechanism for enhanced p21 expression in CCAs. A miR-34a inhibitor reversed the effects of "knocking down" TGFbeta1 on cell growth, migration, cyclin D1, CDK6 and c-Met expression, suggesting that TGFbeta1 mediated effects occur, in part, through this miR-34a signaling pathway. Overexpression of TGFbeta1 was associated with CCA tumor progression. CONCLUSIONS: This study suggests that TGFbeta1 is involved in CCA tumor progression and participates through miR-34a mediated downstream cascades, and is a target to inhibit CCA development and growth. PMID- 27364975 TI - Disrupting VEGF-A paracrine and autocrine loops by targeting SHP-1 suppresses triple negative breast cancer metastasis. AB - Patients with triple-negative breast cancer (TNBC) had an increased likelihood of distant recurrence and death, as compared with those with non-TNBC subtype. Regorafenib is a multi-receptor tyrosine kinase (RTK) inhibitor targeting oncogenesis and has been approved for metastatic colorectal cancer and advanced gastrointestinal stromal tumor. Recent studies suggest regorafenib acts as a SHP 1 phosphatase agonist. Here, we investigated the potential of regorafenib to suppress metastasis of TNBC cells through targeting SHP-1/p-STAT3/VEGF-A axis. We found a significant correlation between cancer cell migration and SHP-1/p STAT3/VEGF-A expression in human TNBC cells. Clinically, high VEGF-A expression is associated with worse disease-free and distant metastasis-free survival. Regorafenib induced significant anti-migratory effects, in association with downregulation of p-STAT3 and VEGF-A. To exclude the role of RTK inhibition in regorafenib-induced anti-metastasis, we synthesized a regorafenib derivative, SC 78, that had minimal effect on VEGFR2 and PDGFR kinase inhibition, while having more potent effects on SHP-1 activation. SC-78 demonstrated superior in vitro and in vivo anti-migration to regorafenib. Furthermore, VEGF-A dependent autocrine/paracrine loops were disrupted by regorafenib and SC-78. This study implies that SHP-1/p-STAT3/VEGF-A axis is a potential therapeutic target for metastatic TNBC, and the more potent SC-78 may be a promising lead for suppressing metastasis of TNBC. PMID- 27364977 TI - Tracheomalacia Due to Esophageal Achalasia. PMID- 27364978 TI - The pregnancy "super-utilizer": how does a high-risk depression screen affect medical utilization? AB - OBJECTIVE: Our objective was to determine whether a score of >11 on the Edinburgh postnatal depression scale (EPDS) at the initial prenatal visit was associated with an increased use of acute medical visits when compared to pregnant women with an initial EPDS score of <=11. METHODS: This was a retrospective cohort study comparing the utilization of acute medical care during pregnancy and the first eight weeks after delivery amongst 200 women with an EPDS score >11 at their initial prenatal visit compared with 200 women with an EPDS score <=11. "Super-utilization" was defined as >=4 acute or unscheduled medical visits during pregnancy and the first eight weeks after delivery (90th percentile). Logistic regression was used to control for confounders. RESULTS: Women with an initial EPDS score >11 were significantly more likely to engage in super-utilization of acute medical care compared with those women scoring <=11 (adjusted odds ratio [aOR], 2.12; 95% confidence interval [CI], 1.53-3.90). CONCLUSIONS: Pregnant women scoring >11 on the EPDS at their initial prenatal visit are more likely to super-utilize acute medical care in the perinatal period. This subset of patients at-risk for increased utilization can be identified early during prenatal care. Interventions to better meet the medical and psychosocial needs of these women warrant future research. PMID- 27364976 TI - A suite of pulse sequences based on multiple sequential acquisitions at one and two radiofrequency channels for solid-state magic-angle spinning NMR studies of proteins. AB - One of the fundamental challenges in the application of solid-state NMR is its limited sensitivity, yet a majority of experiments do not make efficient use of the limited polarization available. The loss in polarization in a single acquisition experiment is mandated by the need to select out a single coherence pathway. In contrast, sequential acquisition strategies can encode more than one pathway in the same experiment or recover unused polarization to supplement a standard experiment. In this article, we present pulse sequences that implement sequential acquisition strategies on one and two radiofrequency channels with a combination of proton and carbon detection to record multiple experiments under magic-angle spinning. We show that complementary 2D experiments such as [Formula: see text] and [Formula: see text] or DARR and [Formula: see text], and 3D experiments such as [Formula: see text] and [Formula: see text], or [Formula: see text] and [Formula: see text] can be combined in a single experiment to ensure time savings of at least 40 %. These experiments can be done under fast or slow moderate magic-angle spinning frequencies aided by windowed [Formula: see text] acquisition and homonulcear decoupling. The pulse sequence suite is further expanded by including pathways that allow the recovery of residual polarization, the so-called 'afterglow' pathways, to encode a number of pulse sequences to aid in assignments and chemical-shift mapping. PMID- 27364979 TI - ATP sensitive potassium channel openers: A new class of ocular hypotensive agents. PMID- 27364980 TI - Two wavelength-dependent mechanisms of sensitisation of light-induced quenching in the isolated light-harvesting complex II. AB - The efficiency of visible light in inducing fluorescence quenching in the isolated light-harvesting complex II (LHCII) of higher plants is investigated by action spectroscopy in the visible portion of photosynthetic active radiation. The efficiency spectrum displays a relatively homogenous quenching yield across the most intense electronic transitions of the chlorophyll a and carotenoid pigments, indicating that quenching proceeds from the equilibrated state of the complex. Larger yields are observed in the 510-640-nm window, where weak transitions of LHCII-bound chromophores occur. This observation is interpreted in terms of an additional quenching sensitisation process mediated by these electronic transitions. PMID- 27364981 TI - Congenital dyserythropoietic anaemia: an unexpected diagnosis in an adult referred with elevated serum ferritin. PMID- 27364982 TI - Low Pretreatment Neutrophil-to-Lymphocyte Ratio Predicts for Good Outcomes in Patients Receiving Neoadjuvant Chemotherapy Before Radical Cystectomy for Muscle Invasive Bladder Cancer. AB - PURPOSE: The pretreatment neutrophil-to-lymphocyte ratio (NLR) has been associated with cancer prognosis, influencing progression and chemosensitivity. We aimed to define the role of the NLR in predicting the outcomes to neoadjuvant chemotherapy (NAC) in patients with muscle invasive bladder cancer (MIBC). PATIENTS AND METHODS: The data from patients treated with NAC and radical cystectomy for MIBC from 2007 to 2015 at a tertiary care center were reviewed. The clinicopathologic pretreatment, including the NLR, and post-treatment predictors were documented. The NLR was evaluated as a continuous variable on uni and multivariate analysis and dichotomized in Kaplan-Meier curves. The relationships with outcomes (progression-free survival [PFS], cancer-specific survival [CSS], and overall survival [OS]) were analyzed using Cox regression analysis and log-rank tests. The pathologic response (PR) included any downstaging from the baseline clinical stage to the final pathologic stage. RESULTS: Of 205 patients with MIBC, 75 underwent NAC (median follow-up, 31 months) with a 5-year PFS, CSS, and OS rate of 56%, 60%, and 52%, respectively, and a PR of 38.6%. On multivariate analysis, the PR, PFS, CSS, and OS were predicted by the NLR (hazard ratio > 0.8, 1.25, 1.27, and 1.12, respectively; P < .05 for all). The NLR with age and clinical stage predicted the PR. A NLR threshold of 2.26 better predicted CSS (P < .05) and OS (P = .055). The limitations included the retrospective design and modest number of cases. CONCLUSION: We have provided initial evidence that a low NLR helps understand the value of the underlying immune system in predicting a good outcome to NAC. The NLR is a simple and accessible biomarker that is easy to implement in clinical practice. In addition to established prognosticators and newer genomic predictors, the NLR could improve therapeutic algorithms and help in decision making regarding the need for NAC, which is currently underused, in MIBC patients. PMID- 27364984 TI - Mechanistic examination of aerobic Pt oxidation: insertion of molecular oxygen into Pt-H bonds through a radical chain mechanism. AB - DFT calculations were performed in an effort to evaluate the mechanism of O2 insertion into the Pt-H bond of Tp(Me2)Pt(IV)Me2H catalyzed by AIBN or light. Results are consistent with a radical chain mechanism involving H loss to form a Pt(III) species followed by addition of O2 to form Pt(III)OO. Subsequent radical propagation involving this Pt(III)OO species and an additional equivalent of the Pt(IV) starting material result in the formation of the observed Pt(IV)OOH and regeneration of the Pt(III). In addition examination of the reaction between AIBN and the Pt(IV) hydroperoxo product demonstrates that radical initiation reactions involving the product occur with a lower barrier than with the initial starting material supporting the idea of autoacceleration in this reaction. Other possible mechanisms were examined in an effort to understand the limited reactivity reported in the absence of light or radical initiators. TDDFT calculations were performed in an effort to understand the reported parallel photo-induced reaction. These calculations found the reactant to be transparent in the relevant light range. An experimental UV-Vis spectrum was obtained and is in agreement with the calculations. PMID- 27364983 TI - [2](1,3)Adamantano[2](2,7)pyrenophane: A Hydrocarbon with a Large Dipole Moment. AB - The fusion of the sp(3) -hybridized parent diamondoid adamantane with the sp(2) hybridized pyrene results in a hybrid structure with a very large dipole moment which arises from bending the pyrene moiety. Presented herein is the synthesis, study of the electronic and optical properties, as well as the dynamic behavior of this new hydrocarbon. PMID- 27364985 TI - Fibrin Association at Hybrid Biointerfaces Made of Clot-Binding Peptides and Polythiophene. AB - The properties as biointerfaces of electroactive conducting polymer-peptide biocomposites formed by poly(3,4-ethylenedioxythiophene) (PEDOT) and CREKA or CR(NMe)EKA peptide sequences (where Glu has been replaced by N-methyl-Glu in the latter) have been compared. CREKA is a linear pentapeptide that recognizes clotted plasma proteins and selectively homes to tumors, while CR(NMe)EKA is an engineer to improve such properties by altering peptide-fibrin interactions. Differences between PEDOT-CREKA and PEDOT-CR(NMe)EKA reflect dissemblance in the organization of the peptides into the polymeric matrix. Both peptides affect fibrinogen thrombin-catalyzed polymerization causing the immediate formation of fibrin, whereas in the absence of thrombin this phenomenon is only observed for CR(NMe)EKA. Consistently, the fibrin-adsorption capacity is higher for PEDOT CR(NMe)EKA than for PEDOT-CREKA, even though in both cases adsorbed fibrin exhibits round-like morphologies rather than the characteristic fibrous structure. PEDOT-peptide films coated with fibrin are selective in terms of cell adhesion, promoting the attachment of metastatic cells with respect to normal cells. PMID- 27364986 TI - Prediction of RF-EMF exposure levels in large outdoor areas through car-mounted measurements on the enveloping roads. AB - Knowledge of spatial and temporal trends in the environmental exposure to radiofrequency electromagnetic fields (RF-EMF) is a key prerequisite for RF-EMF risk assessment studies attempting to establish a link between RF-EMF and potential effects on human health as well as on fauna and flora. In this paper, we determined the validity of RF exposure modelling based on inner-area kriging interpolation of measurements on the surrounding streets. The results vary depending on area size and shape and structural factors; a Spearman coefficient of 0.8 and a relative error of less than 3.5dB are achieved on a data set featuring a closed measurement ring around a decently sized area (1km(2), with an average minimum distance of the encircled area to the ring of less than 100m), containing mainly low, detached buildings. In larger areas, additional inner-area sampling is advised, lowering the average minimum distance between sampled and interpolated locations to 100m, to achieve the same level of accuracy. PMID- 27364987 TI - An approach to comprehensive genome and proteome expression analyses in Schwann cells and neurons during peripheral nerve myelin formation. AB - Peripheral nerve myelination is a complex event resulting from spatially and temporally regulated reciprocal interactions between the neuron and myelin forming Schwann cells. The dynamic process and the protein functional modules and networks that operate throughout the myelination process are poorly understood because of a lack of methodologies suitable for observing specific changes in the Schwann cell/neuron-unit. The identification of the precise roles for the proteins participating in the functional modules and networks that participate in the myelination process is hindered by the cellular and molecular complexity of the nervous tissue itself. We have developed an approach based on a myelinating dorsal root ganglion explant model that allows distinguishing clear, reproducible and predictable differences between the biochemical properties and the genomic and proteomic expression profiles of both cellular components of the Schwann cell/neuron unit at different stages of the myelination process. This model, derived from E13.5 C57BL/6J mouse embryos, is sufficiently robust for use in identifying the protein functional networks and modules related to peripheral nerve myelin formation. The genomic expression profiles of the selected neuronal, Schwann cell and myelin-specific proteins in the cultures reflect in vivo profiles reported in the literature, and the structural and ultrastructural properties of the myelin, as well as the myelination schedule of the cultures, closely resemble those observed in peripheral nerves in situ. The RNA expression data set is available through NCBI gene expression omnibus accession GSE60345. We have developed a reproducible and robust cell culture-based approach, accompanied by a genome-wide expression data set, which allows studying myelination in the peripheral nervous system at the proteomic and transcriptomic levels in Schwann cells and neurons. Myelinating dorsal root explant cultures, prepared from C57BL/6J mouse embryos, present distinct developmental stages comparable to those observed in a peripheral nerve in situ. This model can be used for identifying the protein functional networks and modules related to peripheral nerve myelin formation. PMID- 27364988 TI - Effect of Varying Hemodynamic and Vascular Conditions on Fractional Flow Reserve: An In Vitro Study. AB - BACKGROUND: The aim of this study was to investigate the impact of varying hemodynamic conditions on fractional flow reserve (ratio of pressure distal [Pd] and proximal [Pa] to stenosis under hyperemia) in an in vitro setting. Failure to achieve maximal hyperemia and the choice of hyperemic agents may have differential effects on coronary hemodynamics and, consequently, on the determination of fractional flow reserve. METHODS AND RESULTS: An in vitro flow system was developed to experimentally model the physiological coronary circulation as flow-dependent stenosis resistance in series with variable downstream resistance. Five idealized models with 30% to 70% diameter stenosis severity were fabricated using VeroClear rigid material in an Objet260 Connex printer. Mean aortic pressure was maintained at 7 levels (60-140 mm Hg) from hypotension to hypertension using a needle valve that mimicked adjustable microcirculatory resistance. A range of physiological flow rates was applied by a steady flow pump and titrated by a flow sensor. The pressure drop and the pressure ratio (Pd/Pa) were assessed for the 7 levels of aortic pressure and differing flow rates. The in vitro experimental data were coupled with pressure flow relationships from clinical data for populations with and without myocardial infarction, respectively, to evaluate fractional flow reserve. The curve for pressure ratio and flow rate demonstrated a quadratic relationship with a decreasing slope. The absolute decrease in fractional flow reserve in the group without myocardial infarction (with myocardial infarction) was on the order of 0.03 (0.02), 0.05 (0.02), 0.07 (0.05), 0.17 (0.13) and 0.20 (0.24), respectively, for 30%, 40%, 50%, 60%, and 70% diameter stenosis, for an increase in aortic pressure from 60 to 140 mm Hg. CONCLUSIONS: The fractional flow reserve value, an index of physiological stenosis significance, was observed to decrease with increasing aortic pressure for a given stenosis in this idealized in vitro experiment for vascular groups with and without myocardial infarction. PMID- 27364989 TI - Natural History of Dilated Cardiomyopathy in Children. AB - BACKGROUND: The long-term progression of idiopathic dilated cardiomyopathy (DCM) in pediatric patients compared with adult patients has not been previously characterized. In this study, we compared outcome and long-term progression of pediatric and adult DCM populations. METHODS AND RESULTS: Between 1988 and 2014, 927 DCM patients were consecutively enrolled. The pediatric population (aged <18 years at enrollment) included 47 participants (5.1%). At presentation, the pediatric population compared with adult patients had a significantly increased occurrence of familial forms (P=0.03), shorter duration of heart failure (P=0.04), lower systolic blood pressure (P=0.01), decreased presence of left bundle-branch block (P=0.001), and increased left ventricular ejection fraction (P=0.03). Despite these baseline differences, long-term longitudinal trends of New York Heart Association class III to IV, left ventricular dimensions, left ventricular ejection fraction, and restrictive filling pattern were similar between the 2 populations. Regarding survival analysis, because of the size difference between the 2 populations, we compared the pediatric population with a sample of adult patients randomly matched using the above-mentioned baseline differences in a 3:1 ratio (141 adult versus 47 pediatric patients). During a median follow-up of 110 months, survival free from heart transplantation was significantly lower among pediatric patients compared with adults (P<0.001). Furthermore, pediatric age (ie, <18 years) was found to be associated with an increasing risk of both death from pump failure and life-threatening arrhythmias. CONCLUSIONS: Despite the pediatric DCM population having higher baseline left ventricular ejection fraction and similar long-term echocardiographic progression compared with the adult DCM population, the pediatric DCM patients had worse cardiovascular prognosis. PMID- 27364990 TI - Providing Cardiology Care in Rural Areas Through Visiting Consultant Clinics. AB - BACKGROUND: Workforce experts predict a future shortage of cardiologists that is expected to impact rural areas more severely than urban areas. However, there is little research on how rural patients are currently served through clinical outreach. This study examines the impact of cardiology outreach in Iowa, a state with a large rural population, on participating cardiologists and on patient access. METHODS AND RESULTS: Outreach clinics are tracked annually in the Office of Statewide Clinical Education Programs Visiting Medical Consultant Database (University of Iowa Carver College of Medicine). Data from 2014 were analyzed. In 2014, an estimated 5460 visiting consultant clinic days were provided in 96 predominantly rural cities by 167 cardiologists from Iowa and adjoining states. Forty-five percent of Iowa cardiologists participated in rural outreach. Visiting cardiologists from Iowa and adjoining states drive an estimated 45 000 miles per month. Because of monthly outreach clinics, the average driving time to the nearest cardiologist falls from 42.2+/-20.0 to 14.7+/-11.0 minutes for rural Iowans. Cardiology outreach improves geographic access to office-based cardiology care for more than 1 million Iowans out of a total population of 3 million. Direct travel costs and opportunity costs associated with physician travel are estimated to be more than $2.1 million per year. CONCLUSIONS: Cardiologists in Iowa and adjoining states have expanded access to office-based cardiology care from 18 to 89 of the 99 counties in Iowa. In these 71 counties without a full time cardiologist, visiting consultant clinics can accommodate more than 50% of office visits in the patients' home county. PMID- 27364991 TI - Transglutaminase is a Critical Link Between Inflammation and Hypertension. AB - BACKGROUND: The pathogenesis of essential hypertension is multifactorial with different underlying mechanisms contributing to disease. We have recently shown that TNF superfamily member 14 LIGHT (an acronym for homologous to lymphotoxins, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes, also known as TNFSF14) induces hypertension when injected into mice. Research reported here was undertaken to examine the role of transglutaminase (TGase) in LIGHT-induced hypertension. METHODS AND RESULTS: Initial experiments showed that plasma and kidney TGase activity was induced by LIGHT infusion (13.91+/-2.92 versus 6.75+/-1.92 mU/mL and 19.86+/-3.55 versus 12.00+/-0.97 mU/10 MUg) and was accompanied with hypertension (169+/-7.16 versus 117.17+/-11.57 mm Hg at day 14) and renal impairment (proteinuria, 61.33+/-23.21 versus 20.38+/ 9.01 MUg/mg; osmolality, 879.57+/-93.02 versus 1407.2+/-308.04 mmol/kg). The increase in renal TGase activity corresponded to an increase in RNA for the tissue TGase isoform, termed TG2. Pharmacologically, we showed that LIGHT-induced hypertension and renal impairment did not occur in the presence of cystamine, a well-known competitive inhibitor of TGase activity. Genetically, we showed that LIGHT-mediated induction of TGase, along with hypertension and renal impairment, was dependent on interleukin-6 and endothelial hypoxia inducible factor-1alpha. We also demonstrated that interleukin-6, endothelial hypoxia inducible factor 1alpha, and TGase are required for LIGHT-induced production of angiotensin receptor agonistic autoantibodies. CONCLUSIONS: Thus, LIGHT-induced hypertension, renal impairment, and production of angiotensin receptor agonistic autoantibodies require TGase, most likely the TG2 isoform. Our findings establish TGase as a critical link between inflammation, hypertension, and autoimmunity. PMID- 27364993 TI - Seasonal and decadal patterns in Discostella (Bacillariophyceae) species from bi weekly records of two boreal lakes (Experimental Lakes Area, Ontario, Canada). AB - A recent rise in the relative abundance of Discostella species (D. stelligera and D. pseudostelligera) has been well documented from sedimentary diatom assemblages across the Northern Hemisphere. This unprecedented change over the last ~150 years has been linked to rises in atmospheric temperatures, changes in ice cover, and/or increases in thermal stability, among other factors. The bi-weekly monitoring data from two boreal lakes at the Experimental Lakes Area (ELA) in northwestern Ontario were analyzed across seasons (spring, summer, and fall) and decades (1970s-2000s). We found that Discostella species are primarily spring/early summer bloomers (i.e., late April to June) in these lakes and changes in concentrations of Discostella over time were most pronounced in the spring or early summer months. Increases in Discostella abundance over time may be linked to earlier ice-off and a longer period of spring turnover, resulting from increased winter and spring temperatures. It is also possible that a trophic mismatch between the spring diatom bloom and zooplankton is occurring, thus reducing diatom loss rates, and resulting in greater overall abundance. Moreover, the spring dominance of Discostella in our study lakes occurred at a time of the year when nutrient concentrations were at their highest seasonally, suggesting that these taxa are neither limited directly by nutrients, nor responding to enhanced stratification during the summer months in these lakes. PMID- 27364992 TI - Plasma Macrophage Migration Inhibitor Factor Is Elevated in Response to Myocardial Ischemia. AB - BACKGROUND: Macrophage migration inhibitory factor (MIF) is a key regulator of inflammatory responses, including in the heart. Plasma MIF is elevated early in the course of acute myocardial infarction. In this study, we hypothesized that plasma MIF may also be increased in acute myocardial ischemia. METHODS AND RESULTS: Patients undergoing cardiac stress test (stress nuclear myocardial perfusion scan or stress echocardiography) were recruited. Twenty-two patients had a stress test indicative of myocardial ischemia and were compared with 62 patients who had a negative stress test. Plasma MIF was measured by ELISA before and after the stress test. MIF was also measured in patients with peripheral arterial occlusive disease before and after exercise causing claudication. Gene and protein expression of MIF was measured in mouse cardiac and skeletal muscle tissue by real-time polymerase chain reaction and western blot, respectively. Plasma MIF was elevated at 5 and 15 minutes after stress (relative to before stress) in patients with a positive test, compared with those with a negative test. In contrast, high-sensitivity troponin T and C-reactive protein were not altered after stress in either group. MIF was not altered after exercise in PAOD patients, despite the occurrence of claudication, suggesting that plasma MIF is not a marker for skeletal muscle ischemia. This may be explained by a lower gene and protein expression of MIF in skeletal muscle than the heart. CONCLUSIONS: Our results suggest that plasma MIF is an early marker for acute myocardial ischemia. PMID- 27364994 TI - Naphthoquinone glycosides for bioelectroanalytical enumeration of the faecal indicator Escherichia coli. AB - Microbial water quality monitoring for the presence of faecal indicator bacteria (FIB) is a mandatory activity in many countries and is key in public health protection. Despite technological advances and a need for methodological improvements, chromogenic and fluorogenic enzymatic techniques remain the mainstays of water quality monitoring for both public health agencies and regulated utilities. We demonstrated that bioelectroanalytical approaches to FIB enumeration are possible and can be achieved using commercially available enzyme specific resorufin glycosides, although these are expensive, not widely available or designed for purpose. Following this, we designed two naphthoquinone glycosides which performed better, achieving Escherichia coli detection in the range 5.0 * 102 to 5.0 * 105 CFU ml-1 22-54% quicker than commercially available resorufin glycosides. The molecular design of the naphthoquinone glycosides requires fewer synthetic steps allowing them to be produced for as little as US$50 per kg. Tests with environmental samples demonstrated the low tendency for abiotic interference and that, despite specificity being maintained between beta glucuronidase and beta-galactosidase, accurate enumeration of E. coli in environmental samples necessitates development of a selective medium. In comparison to a commercially available detection method, which has U.S. Environmental Protection Agency (EPA) approval, our approach performed better at high organism concentrations, detecting 500 organisms in 9 h compared with 13.5 h for the commercial method. Bioelectroanalytical detection is comparable to current approved methods and with further development could result in improved detection times. A recent trend for low-cost open-source hardware means that automated, potentiostatically controlled E. coli detection systems could be constructed for less than US$100 per channel. PMID- 27364995 TI - Characterizing the Status (Disturbed, Hybrid or Novel) of Swamp Forest Fragments in a Caribbean Ramsar Wetland: The Impact of Anthropogenic Degradation and Invasive Plant Species. AB - The last remaining Amazonian-type swamp forest fragments in Black River Lower Morass, Jamaica, have been subjected to a myriad of anthropogenic disturbances, compounded by the establishment and spread of several invasive plant species. We established 44 permanent sample plots (covering 3.92 ha) across 10 of these swamp forest fragments and sampled all non-woody plants and all trees >=2 cm DBH found in the plots. These data were used to (1) identify thresholds of hybridity and novelty, (2) derive several diversity and structural descriptors used to characterize the swamp forest fragments and (3) identify possible indicators of anthropogenic degradation. These were incorporated into a framework and used to determine the status of the swamp forest fragments so that appropriate management and conservation measures can be implemented. We recorded 43 woody plant species (9 endemic, 28 native and 4 non-native) and 21 non-tree species. The composition and structure of all the patches differed significantly due to the impact of the herbaceous invasive plant Alpinia allughas, the presence and diversity of other non-native plants, and differing intensities of anthropogenic disturbance (e.g., burning, cutting and harvesting of non-timber forest products). We ranked forest patches along a continuum representing deviations from a historical proxy (least disturbed) swamp forest to those with dramatically altered structural and floristic attributes (=novel swamp forests). Only one fragment overrun with A. allughas was classified as novel. If effective conservation and management does not come to the BRLM, the remaining swamp forest fragments appear doomed to further degradation and will soon disappear altogether. PMID- 27364996 TI - Erratum to: A cohort study of the usefulness of primary prophylaxis in patients with severe haemophilia A. PMID- 27364998 TI - Diffraction response of photorefractive polymers over nine orders of magnitude of pulse duration. AB - The development of a single mode fiber-based pulsed laser with variable pulse duration, energy, and repetition rate has enabled the characterization of photorefractive polymer (PRP) in a previously inaccessible regime located between millisecond and microsecond single pulse illumination. With the addition of CW and nanosecond pulse lasers, four wave mixing measurements covering 9 orders of magnitudes in pulse duration are reported. Reciprocity failure of the diffraction efficiency according to the pulse duration for a constant energy density is observed and attributed to multiple excitation, transport and trapping events of the charge carriers. However, for pulses shorter than 30 MUs, the efficiency reaches a plateau where an increase in energy density no longer affects the efficiency. This plateau is due to the saturation of the charge generation at high peak power given the limited number of sensitizer sites. The same behavior is observed in two different types of devices composed of the same material but with or without a buffer layer covering one electrode, which confirm the origin of these mechanisms. This new type of measurement is especially important to optimize PRP for applications using short pulse duration. PMID- 27364999 TI - ZnO-Based Microcavities Sculpted by Focus Ion Beam Milling. AB - We reported an easy fabrication method to realize ZnO-based microcavities with various cavity shapes by focused ion beam (FIB) milling. The optical characteristics of different shaped microcavities have been systematically carried out and analyzed. Through comprehensive studies of cathodoluminescence and photoluminescence spectra, the whispering gallery mode (WGM) was observed in different shaped microcavities. Up further increasing excitation, the lasing action was dominated by these WGMs and matched very well to the simulated results. Our experiment shows that ZnO microcavities with different shapes can be made with high quality by FIB milling for specific applications of microlight sources and optical devices. PMID- 27364997 TI - Coming of age: the artificial pancreas for type 1 diabetes. AB - The artificial pancreas (closed-loop system) addresses the unmet clinical need for improved glucose control whilst reducing the burden of diabetes self-care in type 1 diabetes. Glucose-responsive insulin delivery above and below a preset insulin amount informed by sensor glucose readings differentiates closed-loop systems from conventional, threshold-suspend and predictive-suspend insulin pump therapy. Insulin requirements in type 1 diabetes can vary between one-third threefold on a daily basis. Closed-loop systems accommodate these variations and mitigate the risk of hypoglycaemia associated with tight glucose control. In this review we focus on the progress being made in the development and evaluation of closed-loop systems in outpatient settings. Randomised transitional studies have shown feasibility and efficacy of closed-loop systems under supervision or remote monitoring. Closed-loop application during free-living, unsupervised conditions by children, adolescents and adults compared with sensor-augmented pumps have shown improved glucose outcomes, reduced hypoglycaemia and positive user acceptance. Innovative approaches to enhance closed-loop performance are discussed and we also present the outlook and strategies used to ease clinical adoption of closed-loop systems. PMID- 27365000 TI - High-Hall-Mobility Al-Doped ZnO Films Having Textured Polycrystalline Structure with a Well-Defined (0001) Orientation. AB - Five hundred-nanometer-thick ZnO-based textured polycrystalline films consisting of 490-nm-thick Al-doped ZnO (AZO) films deposited on 10-nm-thick Ga-doped ZnO (GZO) films exhibited a high Hall mobility (MU H) of 50.1 cm(2)/Vs with a carrier concentration (N) of 2.55 * 10(20) cm(-3). Firstly, the GZO films were prepared on glass substrates by ion plating with dc arc discharge, and the AZO films were then deposited on the GZO films by direct current magnetron sputtering (DC-MS). The GZO interface layers with a preferential c-axis orientation play a critical role in producing AZO films with texture development of a well-defined (0001) orientation, whereas 500-nm-thick AZO films deposited by only DC-MS showed a mixture of the c-plane and the other plane orientation, to exhibit a MU H of 38.7 cm(2)/Vs with an N of 2.22 * 10(20) cm(-3). PMID- 27365001 TI - Porous polymers bearing functional quaternary ammonium salts as efficient solid catalysts for the fixation of CO2 into cyclic carbonates. AB - A series of porous polymers bearing functional quaternary ammonium salts were solvothermally synthesized through the free radical copolymerization of divinylbenzene (DVB) and functionalized quaternary ammonium salts. The obtained polymers feature highly cross-linked matrices, large surface areas, and abundant halogen anions. These polymers were evaluated as heterogeneous catalysts for the synthesis of cyclic carbonates from epoxides and CO2 in the absence of co catalysts and solvents. The results revealed that the synergistic effect between the functional hydroxyl groups and the halide anion Br(-) afforded excellent catalytic activity to cyclic carbonates. In addition, the catalyst can be easily recovered and reused for at least five cycles without significant loss in activity. PMID- 27365002 TI - The effect of healing in the medial collateral ligament of human knee joint: A three-dimensional finite element analysis. AB - The medial collateral ligament (MCL) is one of the main ligaments that provide knee joint with major restraints against valgus, internal, and external torque loads. The MCL injury most frequently occurs near its femoral attachment but can be healed spontaneously. Hence, the usual clinical treatment for MCL injury is conservative therapy with early controlled rehabilitation motion. However, the effect of the variations in the healing conditions of the MCL portion (i.e. near the femoral insertion) is still unclear. In this study, finite element tibiofemoral joint models with three different MCL healing conditions were analyzed under six kinds of joint loads, such as 10 and 20 N.m valgus tibial torques, 5 and 10 N.m internal tibial torques, and 5 and 10 N.m external tibial torques. The three healing conditions corresponded to the early, medium, and final (i.e. healthy) stages of the healing period, respectively. It was found that different MCL healing conditions greatly affected the main joint kinematics under valgus tibial torques, but neither the reaction force nor stress results of the MCL. The peak strain values in the MCL healing portion changed greatly under all the six loads. Moreover, all the joint kinematics, strain results, and reaction force of the MCL at the medium stage were similar to those in the healthy joint, that is, at the final healing stage. These imply that the partially healed MCL might be enough for providing the restraints for knee joints and would not lead to some high strains occurring in the MCL. PMID- 27365004 TI - Crowdsourcing: a valid alternative to expert evaluation of robotic surgery skills. AB - BACKGROUND: Robotic-assisted gynecologic surgery is common, but requires unique training. A validated assessment tool for evaluating trainees' robotic surgery skills is Robotic-Objective Structured Assessments of Technical Skills. OBJECTIVE: We sought to assess whether crowdsourcing can be used as an alternative to expert surgical evaluators in scoring Robotic-Objective Structured Assessments of Technical Skills. STUDY DESIGN: The Robotic Training Network produced the Robotic-Objective Structured Assessments of Technical Skills, which evaluate trainees across 5 dry lab robotic surgical drills. Robotic-Objective Structured Assessments of Technical Skills were previously validated in a study of 105 participants, where dry lab surgical drills were recorded, de-identified, and scored by 3 expert surgeons using the Robotic-Objective Structured Assessments of Technical Skills checklist. Our methods-comparison study uses these previously obtained recordings and expert surgeon scores. Mean scores per participant from each drill were separated into quartiles. Crowdworkers were trained and calibrated on Robotic-Objective Structured Assessments of Technical Skills scoring using a representative recording of a skilled and novice surgeon. Following this, 3 recordings from each scoring quartile for each drill were randomly selected. Crowdworkers evaluated the randomly selected recordings using Robotic-Objective Structured Assessments of Technical Skills. Linear mixed effects models were used to derive mean crowdsourced ratings for each drill. Pearson correlation coefficients were calculated to assess the correlation between crowdsourced and expert surgeons' ratings. RESULTS: In all, 448 crowdworkers reviewed videos from 60 dry lab drills, and completed a total of 2517 Robotic-Objective Structured Assessments of Technical Skills assessments within 16 hours. Crowdsourced Robotic-Objective Structured Assessments of Technical Skills ratings were highly correlated with expert surgeon ratings across each of the 5 dry lab drills (r ranging from 0.75-0.91). CONCLUSION: Crowdsourced assessments of recorded dry lab surgical drills using a validated assessment tool are a rapid and suitable alternative to expert surgeon evaluation. PMID- 27365005 TI - Suprasternal innominate artery cannulation for reoperative aortic surgery: a technical note. AB - Suprasternal cannulation of the innominate artery in aortic reoperations may be useful in specific situations. Over a period of 3.5 years, 9 patients (6 males, average age = 49.2 +/- 16.1 years) underwent suprasternal cannulation prior to resternotomy. Cannulation was performed using a side graft. All operations were successfully completed. Two patients died after surgery because of coagulopathy and multiorgan failure. There were no complications related to access or technique, and no site complications were detected during follow-up. Suprasternal cannulation of the innominate artery may play a role in selected reoperations. PMID- 27365003 TI - Do serial measurements of cervical length improve the prediction of preterm birth in asymptomatic women with twin gestations? AB - BACKGROUND: Cervical length at midtrimester is a powerful predictor of preterm birth in twin gestations. However, given the fact that, in some cases, cervical shortening may become evident only later during the second trimester, it seems reasonable that serial monitoring of cervical length may improve the detection of preterm birth in women with twins. However, data in support of such a practice are limited and conflicting. The contradictory results may be related to the fact that in most of these studies, the analysis of the predictive value of serial measurements of cervical length was limited to data derived from only two sequential measurements of cervical length, while data on the predictive value of multiple (>2) measurements are scarce. OBJECTIVE: We sought to determine whether serial measurements of cervical length can improve the prediction of preterm birth in asymptomatic women with twin gestations compared with a single measurement of cervical length at midgestation. STUDY DESIGN: This was a retrospective cohort study of women with twin pregnancies followed up in a tertiary medical center from 2012 through 2014. All participants underwent routine measurement of cervical length at midgestation and every 2-3 weeks thereafter until 28-32 weeks. For each patient, cervical length was determined at the following time periods: 18+0 to 21+6 weeks (period 1, routine exam), 22+0 to 24+6 weeks (period 2), 25+0 to 27+6 weeks (period 3), and 28+0 to 32+0 weeks (period 4). Measurements of cervical length at periods 2-4 were analyzed in the form of either absolute length (in millimeters) or percent shortening relative to cervical length at period 1. The performance of a stepwise algorithm that incorporated serial measurements of cervical length for the prediction of preterm birth was compared to that achieved with a single measurement of cervical length at period 1. RESULTS: Overall, 441 women with twin pregnancies who were eligible for the study underwent a total of 2374 cervical length measurements. The association of a short cervix (<10th percentile) with preterm birth at <32 weeks persisted in each of the 4 periods of gestation [odds ratio (95% confidence interval): 7.2 (3.1-16.5), 15.3 (6.4-36.7), 10.3 (4.4-24.3), and 23.1(8.3-64.1), respectively]. Compared with a single measurement of cervical length at midgestation (period 1), a stepwise algorithm integrating serial cervical length measurements from all 4 successive gestational age periods resulted in a significant increase in the area under the receiver operating characteristic curve (0.917 vs 0.613, P < .001). Similarly, when a target false-positive rate of 5% was used, the same stepwise algorithm was associated with a higher detection rate (69% vs 28%, P < .001), higher positive likelihood ratio (14.54 vs 5.12), and lower negative likelihood ratio (0.32 vs 0.76) for preterm birth at <32 weeks compared with a single measurement of cervical length at period 1. CONCLUSION: Integration of serial measurements of cervical length using a stepwise algorithm in asymptomatic women with twin gestations can improve the detection of women at risk of preterm birth. Prospective studies are needed to validate these findings, and to investigate whether improved risk assessment performance is sufficient to offset the additional costs associated with serial cervical length measurements. PMID- 27365006 TI - Giant dissecting ventricular septal haematoma associated with critical congenital heart disease. AB - The occurrence of an haematoma in the interventricular septum is very rare. We report a case of a giant interventricular septal haematoma after surgical correction of a critical pulmonary valve stenosis in a newborn with intact ventricular septum. Control echocardiography showed complete resolution of the haematoma at 6-month follow-up. PMID- 27365007 TI - How safe is it to train residents to perform mitral valve surgery? AB - A best evidence topic was constructed according to a structured protocol. The enquiry: In [patients undergoing mitral valve surgery] are [postoperative morbidity and mortality outcomes] acceptable when patients are operated on by [residents]? Four hundred and twenty-three were identified from the search strategy. Six articles selected as best evidence were tabulated. All current published evidence, encompassing open and minimally invasive mitral valve repair in addition to mitral valve replacement, supports the involvement of trainees in mitral procedures. Although trainees may experience longer aortic cross-clamp and cardiopulmonary bypass times than specialist surgeons, they are not associated with significantly worse perioperative or postoperative outcomes in comparable mitral procedures. Important factors in the viability of mitral valve training and its quality include the volume of cases per institution and the expertise of the supervising surgeon, and these remain largely unexplored. Overall, mitral valve surgery remains a valuable potential training opportunity, one which is perhaps underexploited. PMID- 27365008 TI - Determinants of late outcomes in women undergoing mitral repair of myxomatous degeneration. AB - OBJECTIVES: Studies have consistently shown that women have worse perioperative outcomes following mitral surgery compared with men. Few data are available that explain these divergent outcomes. This study was conducted to determine whether women with degenerative mitral valve disease present to surgery with more advanced disease than men, and to determine whether these differences influence long-term clinical outcomes. METHODS: Seven hundred and forty-three patients underwent repair of mitral regurgitation due to myxomatous degeneration between 2001 and 2014. Of these, 208 (28%) were females and concomitant coronary bypass grafting was performed in 103 (14%). The mean clinical follow-up was for 3.1 years, and extended to 11.9 years. RESULTS: Perioperative mortality was 0.1%. Preoperatively, women had a larger indexed left atrial diameter (27.9 +/- 5.7 vs 25.3 +/- 4.7 mm/m2, P = 0.0001), larger indexed left ventricle end-systolic dimension (20.6 +/- 5.5 vs 18.7 +/- 5.1 mm/m2, P = 0.028) and higher right ventricular systolic pressure (44.4 +/- 14.4 vs 41.7 +/- 13.3 mmHg, P = 0.026) compared with men. Five-year survival and freedom from recurrent MR >=2+ were 88.7 +/- 1.8 and 90.7 +/- 1.6%, respectively. Although gender was not associated with survival (hazard ratio: 1.04 +/- 0.4, P = 0.91), women were more likely to develop recurrent MR >=2+ at follow-up compared with men (hazard ratio: 1.9 +/- 0.5, P = 0.007). CONCLUSIONS: In this large series, women with degenerative mitral valve disease presented with echocardiographic markers suggestive of more advanced disease at the time of surgery. Although there was no difference in early or late survival between groups, women were more likely to develop recurrent MR >=2+ over the course of follow-up. Earlier surgical referral of women may, therefore, be advised. PMID- 27365009 TI - Does induction chemoradiotherapy increase survival in patients with Pancoast tumour? AB - A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was whether induction (neoadjuvant) chemoradiotherapy (iCRT) compared with other therapeutic strategies improves survival in patients with Pancoast tumours. Altogether 248 papers were identified using the below-mentioned search. Ten of them represented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group, relevant outcomes and weaknesses were tabulated. Four studies were retrospective comparative studies of induction chemoradiotherapy and surgery (trimodal therapy) versus other therapeutic strategies. Two studies were retrospective and four were prospective investigating trimodal therapy. These papers comprised a total of 550 patients. The overall survival was better with trimodal therapy compared with RT (radiotherapy) followed by surgery group in all three comparative studies. The 2-year survival varied in the trimodal therapy group from 70 to 93%, in comparison to RT group where variation was from 22 to 49%. Five-year survival for trimodal therapy varied between 36.4 and 84% in the results of two comparative studies, compared with 11 and 49% for RT and surgery, respectively. One paper looked at survival in patients who underwent surgery alone [30% at 2-year and 20% at 4-year overall survival (OS)]. The 5-year OS in the retrospective group varied between 38 and 59%. Similar results were reported for the prospective group with 5-year OS between 44 and 56%. Despite a large variation in pCR (complete pathological response) (15-93%) and R0 (77-100%) reported, both represented a positive prognostic factor for survival. Three papers looked at the impact of staging following induction chemoradiotherapy. The majority of patients had T3 disease. An advantage in survival was seen in patients with early disease compared with advanced stage. No randomized controlled trials were identified. All the 10 articles suggested there was a benefit in trimodal therapy with improvement in overall survival. We conclude that combining induction chemoradiotherapy with surgery for Pancoast tumour may offer a survival benefit compared with radiotherapy with surgery or surgery alone. PMID- 27365011 TI - The pragmatic clinical trial in a learning health care system. AB - BACKGROUND/AIMS: A learning health care system ideally incorporates the ability to adapt to the pace of change, the incorporation of new clinical research paradigms, and leverages electronic health record systems and clinical decision support systems to narrow the divide between research and clinical practice. METHODS: An adaptive clinical trial can be embedded into the sites and practice of clinical care in a highly pragmatic way to simultaneously generate high quality data on treatment efficacy and improve the care of patients. This approach can be expanded into a pragmatic platform trial, meaning a trial that is intended to evaluate multiple treatments for a disease or diseases, possibly in combination, and with the available treatments potentially changing over time. This strategy is illustrated using a trial currently being implemented in Europe and funded by the European Union, evaluating three different "domains" of treatments for patients with severe community-acquired pneumonia requiring intensive care. RESULTS: Simulation studies demonstrate that this approach has the potential to save lives while identifying the best treatment strategies for this critically ill population. CONCLUSION: Patients are likely to benefit if we can merge clinical trials and decision support into a single continuous learning process. PMID- 27365010 TI - A framework for analysis of research risks and benefits to participants in standard of care pragmatic clinical trials. AB - BACKGROUND/AIMS: Standard of care pragmatic clinical trials that compare treatments already in use could improve care and reduce costs, but there is considerable debate about the research risks of standard of care pragmatic clinical trials and how to apply informed consent regulations to such trials. We sought to develop a framework integrating the insights from opposing sides of the debate. METHODS: We developed a formal risk-benefit analysis framework for standard of care pragmatic clinical trials and then applied it to key provisions of the US federal regulations. RESULTS: Our formal framework for standard of care pragmatic clinical trial risk-benefit analysis takes into account three key considerations: the ex ante estimates of risks and benefits of the treatments to be compared in a standard of care pragmatic clinical trial, the allocation ratios of treatments inside and outside such a trial, and the significance of some participants receiving a different treatment inside a trial than outside the trial. The framework provides practical guidance on how the research ethics regulations on informed consent should be applied to standard of care pragmatic clinical trials. CONCLUSION: Our proposed formal model makes explicit the relationship between the concepts used by opposing sides of the debate about the research risks of standard of care pragmatic clinical trials and can be used to clarify the implications for informed consent. PMID- 27365012 TI - Patient-reported outcomes questionnaire compliance in Cancer Cooperative Group Trials (Alliance N0992). AB - BACKGROUND/AIMS: The use of patient-reported outcomes in clinical trials is a focal point for research and policy. Non-compliance with planned questionnaires and missing data can threaten both internal validity and generalizability. This retrospective analysis was conducted to determine the extent of, and characteristics associated with, missing patient-reported outcomes. METHODS: Study characteristics, patient characteristics and adverse events, and reasons for non-compliance were compiled from 14 closed Alliance for Clinical Trials in Oncology, Mayo Clinic Cancer Center, or Mayo Clinic Cancer Research Consortium clinical trials. Compliance rates were calculated for each patient using the number of booklets completed while the patient was on trial divided by the number of booklets the patient was expected to complete. Frequency counts and summary statistics were compiled. Logistic regression techniques were employed. RESULTS: The 1640 included patients had a median age of 58 years and were mostly White (90.8%) and female (73.8%). Compliance rates per study ranged from 84.7% to 97.2%. The primary endpoint of overall compliance rate was 93.1%. A total of 1267 patients were compliant. Those non-compliant were slightly older (mean = 58.6 vs 57.5, p = 0.03) and had different types of cancers (p < 0.01). There were no differences in compliance according to tumor status (p = 0.66), clinical stage (p = 0.81), baseline quality of life (p = 0.42 for >=8 vs <8 and p = 0.12 for >=6 vs <6), or maximum adverse event grade incidence (p = 0.33 for grade 2+ incidence and p = 0.36 for grade 3+ incidence). Reasons for non-compliance included patient refusal (N = 136), booklet not administered to patient (N = 199), no clinic visit at the scheduled time for booklet completion (N = 40), and at-home-completed booklet not returned (N = 224). Logistic regression indicates gender (p < 0.01), race (p < 0.01), performance score (p = 0.02), dose delay status (p = 0.01), and incidence of grade 3 or higher adverse event (p = 0.03) were correlates of compliance. CONCLUSION: Patient-reported outcomes have successfully been implemented into Alliance and Mayo Clinic trials with high rates of patient compliance. Further improvement in compliance can be made with staff commitment and education. Patients are typically non-compliant only when the task at hand is burdensome, unclear, or logistically challenging. Existing tracking systems used for the other trial outcomes should be utilized to ensure successful capture of patient-reported outcomes. PMID- 27365014 TI - Statistical issues in the design, conduct and analysis of two large safety studies. AB - BACKGROUND/AIMS: The emergence, post approval, of serious medical events, which may be associated with the use of a particular drug or class of drugs, is an important public health and regulatory issue. The best method to address this issue is through a large, rigorously designed safety study. Therefore, it is important to elucidate the statistical issues involved in these large safety studies. METHODS: Two such studies are PRECISION and EAGLES. PRECISION is the primary focus of this article. PRECISION is a non-inferiority design with a clinically relevant non-inferiority margin. Statistical issues in the design, conduct and analysis of PRECISION are discussed. RESULTS: Quantitative and clinical aspects of the selection of the composite primary endpoint, the determination and role of the non-inferiority margin in a large safety study and the intent-to-treat and modified intent-to-treat analyses in a non-inferiority safety study are shown. Protocol changes that were necessary during the conduct of PRECISION are discussed from a statistical perspective. Issues regarding the complex analysis and interpretation of the results of PRECISION are outlined. EAGLES is presented as a large, rigorously designed safety study when a non inferiority margin was not able to be determined by a strong clinical/scientific method. In general, when a non-inferiority margin is not able to be determined, the width of the 95% confidence interval is a way to size the study and to assess the cost-benefit of relative trial size. CONCLUSION: A non-inferiority margin, when able to be determined by a strong scientific method, should be included in a large safety study. Although these studies could not be called "pragmatic," they are examples of best real-world designs to address safety and regulatory concerns. PMID- 27365013 TI - Use of administrative data to increase the practicality of clinical trials: Insights from the Women's Health Initiative. AB - BACKGROUND: To reduce research costs in the context of pragmatic trials, consideration is given to using administrative data (Medicare claims) to ascertain clinical outcomes. METHODS: In the historical context of the Women's Health Initiative, the correspondence between selected cardiovascular events derived from Medicare claims was compared to those documented and adjudicated in this large-scale prevention trial. RESULTS: Classification performance varies somewhat by type of outcome, but hazard ratios and confidence intervals derived from the two data sources were quite comparable. CONCLUSION: These encouraging results provided the needed support to launch a new embedded pragmatic trial of physical activity that will rely heavily on Medicare claims to ascertain cardiovascular disease incidence in the majority of those randomized. PMID- 27365015 TI - Statistical issues in pragmatic trials of behavioral economic interventions. AB - BACKGROUND: Randomized clinical trials provide gold-standard evidence for the efficacy of interventions, but have limitations, including highly selected populations that make inference on effectiveness difficult and a lack of ability to adapt and change midstream. METHODS: We propose two innovations for pragmatic trial design. RESULTS: Evidence-based evolutionary testing, a framework that allows adaptation of interventions and rapid-cycle innovation, preserves the power of randomization while acknowledging the need for adaptation and learning. An opt-out consent framework increases the fraction of the target population who participate in trials, but may lead to dampening of effect sizes. CONCLUSION: Pragmatic trials offer numerous advantages in the evaluation of behavioral interventions in health. Statistical innovations, including evidence-based evolutionary testing and opt-out framing of consent and enrollment processes, can enhance the power of pragmatic trials and lead to more rapid progress. PMID- 27365016 TI - Response. PMID- 27365017 TI - Comments on Berry et al.'s response-adaptive randomization platform trial for Ebola. PMID- 27365018 TI - Unforeseen rib fracture findings in infant chest radiographs: evidence of non accidental injury or simply a case of birth trauma? PMID- 27365019 TI - PET monitoring of liver directed selective internal radionuclide therapy for metastatic gastro-oesophageal cancer. PMID- 27365020 TI - Atretic parietal encephalocoele. PMID- 27365021 TI - Ultra-wide field imaging of bilateral idiopathic retinal dialysis. PMID- 27365022 TI - [German Rheumatism Research Center in Berlin : A Leibniz institute]. PMID- 27365023 TI - [Update on kinase inhibitors]. PMID- 27365024 TI - [Biologics]. PMID- 27365025 TI - [Classification criteria for rheumatic diseases]. PMID- 27365026 TI - [Treat to target and personalized medicine (precision medicine)]. PMID- 27365027 TI - [Methotrexate]. PMID- 27365028 TI - [Molecular physical medicine in rheumatic disease patterns]. PMID- 27365029 TI - Definitions, Foundations and Associations of Physical Literacy: A Systematic Review. AB - BACKGROUND: The concept of physical literacy has stimulated increased research attention in recent years-being deployed in physical education, sport participation, and the promotion of physical activity. Independent research groups currently operationalize the construct differently. OBJECTIVE: The purpose of this systematic review was to conduct a systematic review of the physical literacy construct, as reflected in contemporary research literature. METHODS: Five databases were searched using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines for systematic reviews. Inclusion criteria were English language, peer reviewed, published by March 2016, and seeking to conceptualize physical literacy. Articles that met these criteria were analyzed in relation to three core areas: properties/attributes, philosophical foundations and theoretical associations with other constructs. A total of 50 published articles met the inclusion criteria and were analyzed qualitatively using inductive thematic analysis. RESULTS: The thematic analysis addressed the three core areas. Under definitions, core attributes that define physical literacy were identified, as well as areas of conflict between different approaches currently being adopted. One relatively clear philosophical approach was prominent in approximately half of the papers, based on a monist/holistic ontology and phenomenological epistemology. Finally, the analysis identified a number of theoretical associations, including health, physical activity and academic performance. CONCLUSIONS: Current literature contains different representations of the physical literacy construct. The costs and benefits of adopting an exclusive approach versus pluralism are considered. Recommendations for both researchers and practitioners focus on identifying and clearly articulating the definitions, philosophical assumptions and expected outcomes prior to evaluating the effectiveness of this emerging concept. PMID- 27365030 TI - Introduction to biosensors. AB - Biosensors are nowadays ubiquitous in biomedical diagnosis as well as a wide range of other areas such as point-of-care monitoring of treatment and disease progression, environmental monitoring, food control, drug discovery, forensics and biomedical research. A wide range of techniques can be used for the development of biosensors. Their coupling with high-affinity biomolecules allows the sensitive and selective detection of a range of analytes. We give a general introduction to biosensors and biosensing technologies, including a brief historical overview, introducing key developments in the field and illustrating the breadth of biomolecular sensing strategies and the expansion of nanotechnological approaches that are now available. PMID- 27365031 TI - Antibodies and antibody-derived analytical biosensors. AB - The rapid diagnosis of many diseases and timely initiation of appropriate treatment are critical determinants that promote optimal clinical outcomes and general public health. Biosensors are now being applied for rapid diagnostics due to their capacity for point-of-care use with minimum need for operator input. Antibody-based biosensors or immunosensors have revolutionized diagnostics for the detection of a plethora of analytes such as disease markers, food and environmental contaminants, biological warfare agents and illicit drugs. Antibodies are ideal biorecognition elements that provide sensors with high specificity and sensitivity. This review describes monoclonal and recombinant antibodies and different immobilization approaches crucial for antibody utilization in biosensors. Examples of applications of a variety of antibody based sensor formats are also described. PMID- 27365032 TI - Non-antibody protein-based biosensors. AB - Biosensors that depend on a physical or chemical measurement can be adversely affected by non-specific interactions. For example, a biosensor designed to measure specifically the levels of a rare analyte can give false positive results if there is even a small amount of interaction with a highly abundant but irrelevant molecule. To overcome this limitation, the biosensor community has frequently turned to antibody molecules as recognition elements because they are renowned for their exquisite specificity. Unfortunately antibodies can often fail when immobilised on inorganic surfaces, and alternative biological recognition elements are needed. This article reviews the available non-antibody-binding proteins that have been successfully used in electrical and micro-mechanical biosensor platforms. PMID- 27365033 TI - Oligonucleotide-based systems: DNA, microRNAs, DNA/RNA aptamers. AB - There are an increasing number of applications that have been developed for oligonucleotide-based biosensing systems in genetics and biomedicine. Oligonucleotide-based biosensors are those where the probe to capture the analyte is a strand of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) or a synthetic analogue of naturally occurring nucleic acids. This review will shed light on various types of nucleic acids such as DNA and RNA (particularly microRNAs), their role and their application in biosensing. It will also cover DNA/RNA aptamers, which can be used as bioreceptors for a wide range of targets such as proteins, small molecules, bacteria and even cells. It will also highlight how the invention of synthetic oligonucleotides such as peptide nucleic acid (PNA) or locked nucleic acid (LNA) has pushed the limits of molecular biology and biosensor development to new perspectives. These technologies are very promising albeit still in need of development in order to bridge the gap between the laboratory-based status and the reality of biomedical applications. PMID- 27365034 TI - Glycan and lectin biosensors. AB - A short description about the importance of glycan biorecognition in physiological (blood cell type) and pathological processes (infections by human and avian influenza viruses) is provided in this review. Glycans are described as much better information storage media, compared to proteins or DNA, due to the extensive variability of glycan structures. Techniques able to detect an exact glycan structure are briefly discussed with the main focus on the application of lectins (glycan-recognising proteins) in the specific analysis of glycans still attached to proteins or cells/viruses. Optical, electrochemical, piezoelectric and micromechanical biosensors with immobilised lectins or glycans able to detect a wide range of analytes including whole cells/viruses are also discussed. PMID- 27365035 TI - Use of biosensors for the detection of marine toxins. AB - Increasing occurrences of harmful algal blooms (HABs) in the ocean are a major concern for countries around the globe, and with strong links between HABs and climate change and eutrophication, the occurrences are only set to increase. Of particular concern with regard to HABs is the presence of toxin-producing algae. Six major marine biotoxin groups are associated with HABs. Ingestion of such toxins via contaminated shellfish, fish, or other potential vectors, can lead to intoxication syndromes with moderate to severe symptoms, including death in extreme cases. There are also major economic implications associated with the diverse effects of marine biotoxins and HABs. Thus, effective monitoring programmes are required to manage and mitigate their detrimental global effect. However, currently legislated detection methods are labour-intensive, expensive and relatively slow. The growing field of biosensor diagnostic devices is an exciting area that has the potential to produce robust, easy-to-use, cost effective, rapid and accurate detection methods for marine biotoxins and HABs. This review discusses recently developed biosensor assays that target marine biotoxins and their microbial producers, both in harvested fish/shellfish samples and in the open ocean. The effective deployment of such biosensor platforms could address the pressing need for improved monitoring of HABs and marine biotoxins, and could help to reduce their global economic impact. PMID- 27365036 TI - Bioconjugation and stabilisation of biomolecules in biosensors. AB - Suitable bioconjugation strategies and stabilisation of biomolecules on electrodes is essential for the development of novel and commercially viable biosensors. In the present review, the functional groups that comprise the selectable targets for practical bioconjugation methods are discussed. We focus on describing the most common immobilisation techniques used in biosensor construction, which are classified into irreversible and reversible methods. Concerning the stability of proteins, the two main types of stability may be defined as (i) storage or shelf stability, and (ii) operational stability. Both types of stability are explained, as well as the introduction of an electrophoretic technique for predicting protein-polymer interactions. In addition, solution and dry stabilisation as well as stabilisation using the covalent immobilisation of proteins are discussed including possible factors that influence stability. Finally, the integration of nanomaterials, such as magnetic particles, with protein immobilisation is discussed in relation to protein stability studies. PMID- 27365037 TI - Electrochemical biosensors and nanobiosensors. AB - Electrochemical techniques have great promise for low-cost miniaturised easy-to use portable devices for a wide range of applications-in particular, medical diagnosis and environmental monitoring. Different techniques can be used for biosensing, with amperometric devices taking the central role due to their widespread application in glucose monitoring. In fact, glucose biosensing takes an approximately 70% share of the biosensor market due to the need for diabetic patients to monitor their sugar levels several times a day, making it an appealing commercial market.In this review, we present the basic principles of electrochemical biosensor devices. A description of the different generations of glucose sensors is used to describe in some detail the operation of amperometric sensors and how the introduction of mediators can enhance the performance of the sensors. Electrochemical impedance spectroscopy is a technique being increasingly used in devices due to its ability to detect variations in resistance and capacitance upon binding events. Novel advances in electrochemical sensors, due to the use of nanomaterials such as carbon nanotubes and graphene, are presented as well as future directions that the field is taking. PMID- 27365038 TI - Biologically sensitive field-effect transistors: from ISFETs to NanoFETs. AB - Biologically sensitive field-effect transistors (BioFETs) are one of the most abundant classes of electronic sensors for biomolecular detection. Most of the time these sensors are realized as classical ion-sensitive field-effect transistors (ISFETs) having non-metallized gate dielectrics facing an electrolyte solution. In ISFETs, a semiconductor material is used as the active transducer element covered by a gate dielectric layer which is electronically sensitive to the (bio-)chemical changes that occur on its surface. This review will provide a brief overview of the history of ISFET biosensors with general operation concepts and sensing mechanisms. We also discuss silicon nanowire-based ISFETs (SiNW FETs) as the modern nanoscale version of classical ISFETs, as well as strategies to functionalize them with biologically sensitive layers. We include in our discussion other ISFET types based on nanomaterials such as carbon nanotubes, metal oxides and so on. The latest examples of highly sensitive label-free detection of deoxyribonucleic acid (DNA) molecules using SiNW FETs and single cell recordings for drug screening and other applications of ISFETs will be highlighted. Finally, we suggest new device platforms and newly developed, miniaturized read-out tools with multichannel potentiometric and impedimetric measurement capabilities for future biomedical applications. PMID- 27365039 TI - Optical biosensors. AB - Optical biosensors represent the most common type of biosensor. Here we provide a brief classification, a description of underlying principles of operation and their bioanalytical applications. The main focus is placed on the most widely used optical biosensors which are surface plasmon resonance (SPR)-based biosensors including SPR imaging and localized SPR. In addition, other optical biosensor systems are described, such as evanescent wave fluorescence and bioluminescent optical fibre biosensors, as well as interferometric, ellipsometric and reflectometric interference spectroscopy and surface-enhanced Raman scattering biosensors. The optical biosensors discussed here allow the sensitive and selective detection of a wide range of analytes including viruses, toxins, drugs, antibodies, tumour biomarkers and tumour cells. PMID- 27365040 TI - Acoustic biosensors. AB - Resonant and acoustic wave devices have been researched for several decades for application in the gravimetric sensing of a variety of biological and chemical analytes. These devices operate by coupling the measurand (e.g. analyte adsorption) as a modulation in the physical properties of the acoustic wave (e.g. resonant frequency, acoustic velocity, dissipation) that can then be correlated with the amount of adsorbed analyte. These devices can also be miniaturized with advantages in terms of cost, size and scalability, as well as potential additional features including integration with microfluidics and electronics, scaled sensitivities associated with smaller dimensions and higher operational frequencies, the ability to multiplex detection across arrays of hundreds of devices embedded in a single chip, increased throughput and the ability to interrogate a wider range of modes including within the same device. Additionally, device fabrication is often compatible with semiconductor volume batch manufacturing techniques enabling cost scalability and a high degree of precision and reproducibility in the manufacturing process. Integration with microfluidics handling also enables suitable sample pre processing/separation/purification/amplification steps that could improve selectivity and the overall signal-to-noise ratio. Three device types are reviewed here: (i) bulk acoustic wave sensors, (ii) surface acoustic wave sensors, and (iii) micro/nano-electromechanical system (MEMS/NEMS) sensors. PMID- 27365041 TI - Lateral flow assays. AB - Lateral flow assays (LFAs) are the technology behind low-cost, simple, rapid and portable detection devices popular in biomedicine, agriculture, food and environmental sciences. This review presents an overview of the principle of the method and the critical components of the assay, focusing on lateral flow immunoassays. This type of assay has recently attracted considerable interest because of its potential to provide instantaneous diagnosis directly to patients. The range and interpretation of results and parameters used for evaluation of the assay will also be discussed. The main advantages and disadvantages of LFAs will be summarized and relevant future improvements to testing devices and strategies will be proposed. Finally, the major recent advances and future diagnostic applications in the LFA field will be explored. PMID- 27365042 TI - Lab-on-chip systems for integrated bioanalyses. AB - Biomolecular detection systems based on microfluidics are often called lab-on chip systems. To fully benefit from the miniaturization resulting from microfluidics, one aims to develop 'from sample-to-answer' analytical systems, in which the input is a raw or minimally processed biological, food/feed or environmental sample and the output is a quantitative or qualitative assessment of one or more analytes of interest. In general, such systems will require the integration of several steps or operations to perform their function. This review will discuss these stages of operation, including fluidic handling, which assures that the desired fluid arrives at a specific location at the right time and under the appropriate flow conditions; molecular recognition, which allows the capture of specific analytes at precise locations on the chip; transduction of the molecular recognition event into a measurable signal; sample preparation upstream from analyte capture; and signal amplification procedures to increase sensitivity. Seamless integration of the different stages is required to achieve a point-of-care/point-of-use lab-on-chip device that allows analyte detection at the relevant sensitivity ranges, with a competitive analysis time and cost. PMID- 27365043 TI - Protective Effects of Intralipid and Caffeic Acid Phenethyl Ester (CAPE) on Hepatotoxicity and Pancreatic Injury Caused by Dichlorvos in Rats. AB - The present study was aimed to the investigate the protective effects of caffeic acid phenethyl ester (CAPE) and intralipid (IL) on hepatotoxicity and pancreatic injury caused by acute dichlorvos (D) intoxication in rats. Forty-eight Wistar rats were randomly divided into seven groups each containing seven rats except control groups. The groups included control, D, CAPE, IL, D + CAPE, D + IL, and D + CAPE + IL. Total antioxidant status and total oxidative stress levels were measured by automated colorimetric assay. Tissues were evaluated using hematoxylin and eosin (H&E) staining. Tissues were analyzed with hematoxylin and eosin by using standard protocols. Also, Bcl-2, Bax and caspase-3 were evaluated by immunohistochemical method in liver tissue. Total oxidant status in control, CAPE, and IL groups were significantly lower, and total antioxidant status in the D + CAPE, D + IL, and D + IL + CAPE groups were significantly higher compared to the D group. CAPE and IL treatment decreased the apoptotic and mitotic cell count in liver tissue. Parenchymal necrosis caused by dichlorvos is observed in pancreas tissues of rats. Mild congestion and edema formation occurred in pancreas tissues following D + CAPE and D + IL therapies. These results indicate that CAPE and IL have the potential to decrease oxidative stress and hepatic and pancreatic injuries caused by acute dichlorvos intoxication. These drugs can be considered as a new method for supportive and protective therapy against pesticide intoxication. PMID- 27365044 TI - Evaluation of Local CYP17A1 and CYP19A1 Expression Levels as Prognostic Factors in Postmenopausal Invasive Ductal Breast Cancer Cases. AB - There is growing attention focused on local estrogen production in the breast tissue and its possible role in breast cancer initiation and progression. Understanding the underlying mechanisms for estrogen synthesis and the microenvironment consisting of tumor and its surrounding adipose tissue might open new avenues in breast cancer prevention, prognosis and treatment. In order to obtain insight, we compared peritumoral and tumor tissue expressions of CYP17A1 and CYP19A1 genes, which play an important role in estrogen biosynthesis. The paired tissue samples of 20 postmenopausal ER+/PR+ patients diagnosed with invasive ductal breast cancer were studied. In addition, 12 breast tissue samples obtained from premenopausal women without a history of breast cancer were also investigated as representative of normal conditions. Peritumoral adipose tissues expressed CYP19A1 approximately threefold higher than tumor itself (p = 0.001). A nonsignificant trend toward low expression of CYP17A1 was observed in peritumoral compared to tumor tissue (p = 0.687). Clinicopathological parameters and patient characteristics which are accepted as risk factors for breast cancer were also associated with individual and combined expressions of CYP17A1 and CYP19A1. This study offers that evaluation of CYP17A1 and CYP19A1 local expression levels might be useful for deciding on personalized treatment approaches and more accurate diagnosis, when evaluated together with several clinicopathological and disease risk factors. Considering the key role of these CYPs in estrogen synthesis, determining their expression levels may be useful as a postdiagnostic marker and for choosing the right treatment method in addition to the conventional approach. PMID- 27365045 TI - Set a low bar for starting palliative care. PMID- 27365046 TI - Extensive ceRNA-ceRNA interaction networks mediated by miRNAs regulate development in multiple rhesus tissues. AB - Crosstalk between RNAs mediated by shared microRNAs (miRNAs) represents a novel layer of gene regulation, which plays important roles in development. In this study, we analyzed time series expression data for coding genes and long non coding RNAs (lncRNAs) to identify thousands of interactions among competitive endogenous RNAs (ceRNAs) in four rhesus tissues. The ceRNAs exhibited dynamic expression and regulatory patterns during each tissue development process, which suggests that ceRNAs might work synergistically during different developmental stages or tissues to control specific functions. In addition, lncRNAs exhibit higher specificity as ceRNAs than coding-genes and their functions were predicted based on their competitive coding-gene partners to discover their important developmental roles. In addition to the specificity of tissue development, functional analyses demonstrated that the combined effects of multiple ceRNAs can have major impacts on general developmental and metabolic processes in multiple tissues, especially transcription-related functions where competitive interactions. Moreover, ceRNA interactions could sequentially and/or synergistically mediate the crosstalk among different signaling pathways during brain development. Analyzing ceRNA interactions during the development of multiple tissues will provideinsights in the regulation of normal development and the dysregulation of key mechanisms during pathogenesis. PMID- 27365047 TI - Sam68 functions as a transcriptional coactivator of the p53 tumor suppressor. AB - Sam68 is a known sequence-specific RNA binding protein that regulates alternative splicing events during the cell cycle and apoptosis. Sam68 has also been shown to influence transcription, but the molecular mechanism remains undefined. Herein we identify Sam68 as a transcriptional coactivator of the p53 tumor suppressor in response to DNA damage. Using CRISPR/Cas9 generated isogenic HCT116 Sam68-/- cell lines wild type or deficient for p53, we show that Sam68 is required for the efficient transactivation of p53 target genes. Consistently, Sam68 depletion caused defects in DNA damage-induced cell cycle arrest and apoptosis mediated by p53. Mechanistically, we demonstrate that Sam68 physically interacted with p53 in an RNA-dependent manner, and that this interaction was essential for the coactivator function of Sam68. Furthermore, we show that both Sam68 and p53 were recruited to promoters of p53-responsive genes, suggesting interdependence. Finally, Sam68 acted in concert with the p53 long noncoding RNA (lncRNA) target PR-lncRNA-1 for p53 recruitment, implicating a positive-feedback mechanism in which lncRNAs induced by the Sam68/p53 complex can enhance p53 transcriptional activity. These findings define a hitherto novel mechanism of action for Sam68 in governing p53 transcriptional activation, and represent the first report of Sam68 in the regulation of tumor suppressor activities. PMID- 27365049 TI - The role of sequence context, nucleotide pool balance and stress in 2' deoxynucleotide misincorporation in viral, bacterial and mammalian RNA. AB - The misincorporation of 2'-deoxyribonucleotides (dNs) into RNA has important implications for the function of non-coding RNAs, the translational fidelity of coding RNAs and the mutagenic evolution of viral RNA genomes. However, quantitative appreciation for the degree to which dN misincorporation occurs is limited by the lack of analytical tools. Here, we report a method to hydrolyze RNA to release 2'-deoxyribonucleotide-ribonucleotide pairs (dNrN) that are then quantified by chromatography-coupled mass spectrometry (LC-MS). Using this platform, we found misincorporated dNs occurring at 1 per 103 to 105 ribonucleotide (nt) in mRNA, rRNAs and tRNA in human cells, Escherichia coli, Saccharomyces cerevisiae and, most abundantly, in the RNA genome of dengue virus. The frequency of dNs varied widely among organisms and sequence contexts, and partly reflected the in vitro discrimination efficiencies of different RNA polymerases against 2'-deoxyribonucleoside 5'-triphosphates (dNTPs). Further, we demonstrate a strong link between dN frequencies in RNA and the balance of dNTPs and ribonucleoside 5'-triphosphates (rNTPs) in the cellular pool, with significant stress-induced variation of dN incorporation. Potential implications of dNs in RNA are discussed, including the possibilities of dN incorporation in RNA as a contributing factor in viral evolution and human disease, and as a host immune defense mechanism against viral infections. PMID- 27365050 TI - Chromatin structure-dependent conformations of the H1 CTD. AB - Linker histones are an integral component of chromatin but how these proteins promote assembly of chromatin fibers and higher order structures and regulate gene expression remains an open question. Using Forster resonance energy transfer (FRET) approaches we find that association of a linker histone with oligonucleosomal arrays induces condensation of the intrinsically disordered H1 CTD in a manner consistent with adoption of a defined fold or ensemble of folds in the bound state. However, H1 CTD structure when bound to nucleosomes in arrays is distinct from that induced upon H1 association with mononucleosomes or bare double stranded DNA. Moreover, the H1 CTD becomes more condensed upon condensation of extended nucleosome arrays to the contacting zig-zag form found in moderate salts, but does not detectably change during folding to fully compacted chromatin fibers. We provide evidence that linker DNA conformation is a key determinant of H1 CTD structure and that constraints imposed by neighboring nucleosomes cause linker DNAs to adopt distinct trajectories in oligonucleosomes compared to H1-bound mononucleosomes. Finally, inter-molecular FRET between H1s within fully condensed nucleosome arrays suggests a regular spatial arrangement for the H1 CTD within the 30 nm chromatin fiber. PMID- 27365048 TI - Chromosome territory relocation during DNA repair requires nuclear myosin 1 recruitment to chromatin mediated by Upsilon-H2AX signaling. AB - During DNA damage response (DDR), certain gene rich chromosome territories (CTs) relocate to newer positions within interphase nuclei and revert to their native locations following repair. Such dynamic relocation of CTs has been observed under various cellular conditions, however, the underlying mechanistic basis of the same has remained largely elusive. In this study, we aim to understand the temporal and molecular details of such crosstalk between DDR signaling and CT relocation dynamics. We demonstrate that signaling at DNA double strand breaks (DSBs) by the phosphorylated histone variant (Upsilon-H2AX) is a pre-requisite for damage induced CT relocation, as cells deficient in Upsilon-H2AX signaling fail to exhibit such a response. Inhibition of Rad51 or DNA Ligase IV mediated late steps of double strand break repair does not seem to abrogate CT relocation completely. Upon DNA damage, an increase in the levels of chromatin bound motor protein nuclear myosin 1 (NM1) ensues, which appears to be functionally linked to Upsilon-H2AX signaling. Importantly, the motor function of NM1 is essential for its recruitment to chromatin and CT relocation following damage. Taking these observations together, we propose that early DDR sensing and signaling result in NM1 recruitment to chromosomes which in turn guides DNA damage induced CT relocation. PMID- 27365051 TI - A method for fast safety screening of explosives in terms of crystal packing and molecular stability. AB - Safety prediction is crucial to the molecular design or the material design of explosives, and the predictions based on any single factor alone will cause much inaccuracy, leading to a desire for a method on multi-bases. The presented proposes an improved method for fast screening explosive safety by combining a crystal packing factor and a molecular one, that is, steric hindrance against shear slide in crystal and molecular stability, denoted by intermolecular friction symbol (IFS) and bond dissociation energy (BDE) of trigger linkage respectively. Employing this BDE-IFS combined method, we understand the impact sensitivities of 24 existing explosives, and predict those of two energetic energetic cocrystals of the observed CL-20/BTF and the supposed HMX/TATB. As a result, a better understanding is implemented by the combined method relative to molecular stability alone, verifying its improvement of more accurate predictions and the feasibility of IFS to graphically reflect molecular stacking in crystals. Also, this work verifies that the explosive safety is strongly related with its crystal stacking, which determines steric hindrance and influences shear slide. PMID- 27365052 TI - Optimal cytoreduction, depth of myometrial invasion, and age are independent prognostic factors for survival in women with uterine papillary serous and clear cell carcinomas. AB - OBJECTIVE: The purpose of this study was to investigate the clinicopathological characteristics, treatment methods, and prognostic factors in women with uterine papillary serous carcinoma (UPSC) and uterine clear-cell carcinoma (UCCC). STUDY DESIGN: All patients who had undergone surgery for UPCS and UCCC between January 1995 and December 2012 were retrospectively reviewed. Patients with missing data, who did not undergo surgical staging and patients with mixed tumor histology were excluded. Multivariate regression models were used to identify the risk factors for overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 49 UPSC and 22 UCCC women were included. The majority of the patients were at stage I [IA, 22 (31%) and IB, 18 (25.4%)]. Stages II, III, and IV were identified in 9 (12.7%), 13 (18.3%), and 9 (12.7%) of cases, respectively. Optimal cytoreduction was achieved in 71.8% of cases. Recurrences occurred in 16 patients (22.5%). The 5-year OS rates were 67% for UPSC; 76% for UCCC; 68% for both histology, respectively. Multivariate analysis pointed out that age>67 years (odds ratio (OR): 3.85, p = 0.009 and OR: 3.35, p = 0.014), >50% myometrial invasion (MI) (OR: 2.87, p = 0.037 and OR: 2.46, p = 0.046) and optimal cytoreduction (OR: 3.26, p = 0.006 and OR: 2.77, p = 0.015) were the independent prognostic factors for both PFS and OS. CONCLUSIONS: Our study demonstrated that optimal cytoreduction, >50% MI, and age >67 years are the most significant factors affecting survival in women with UPSC and UCCC. PMID- 27365053 TI - An 8-hydroxyquinoline-containing polymeric micelle system is effective for the treatment of murine tegumentary leishmaniasis. AB - The current treatment of leishmaniasis has been hampered due to the high toxicity of the available drugs and long duration protocols, which often lead to its abandonment. In the present study, a poloxamer 407-based delivery system was developed, and a molecule, 8-hydroxyquinoline (8-HQN), was incorporated with it, leading to an 8-HQN/micelle (8-HQN/M) composition. Assays were performed to evaluate the in vitro antileishmanial activity of 8-HQN/M against Leishmania amazonensis stationary promastigotes. The cytotoxicity in murine macrophages and in human red cells, as well as the efficacy of the treatment in macrophages infected by parasites, was also assessed. This product was also evaluated for the treatment of murine tegumentary leishmaniasis, using L. amazonensis-infected BALB/c mice. To evaluate the in vivo efficacy of the treatment, the average lesion diameter (area) in the infected tissue, as well as the parasite load at the site of infection (skin), spleen, liver and draining lymph nodes were examined. Non-incorporated micelle (B-8-HQN/M) and the free molecule (8-HQN) were used as controls, besides animals that received only saline. The parasite burden was evaluated by limiting dilution and quantitative real-time PCR (qPCR) techniques, and immunological parameters associated with the treatments were also investigated. In the results, the 8-HQN/M group, when compared to the others, presented more significant reductions in the average lesion diameter and in the parasite burden in the skin and all evaluated organs. These animals also showed significantly higher levels of parasite-specific IFN-gamma, IL-12, and GM-CSF, associated with low levels of IL-4 and IL-10, when compared to the saline, 8 HQN/M, and B-8-HQN groups. A predominant IL-12-driven IFN-gamma production, against parasite proteins, mainly produced by CD4+ T cells, was observed in the treated animals, post-infection. In conclusion, 8-HQN/M was highly effective in treating L. amazonensis-infected BALB/c mice and can be considered alone, or combined with other drugs, as an alternative treatment for tegumentary leishmaniasis. Graphical Abstract Therapeutic scheme and immunological and parasitological parameters developed in the present study. PMID- 27365055 TI - Hypoxic inactivation of glycogen synthase kinase-3beta promotes gastric tumor growth and angiogenesis by facilitating hypoxia-inducible factor-1 signaling. AB - Since the molecular mechanism of hypoxic adaptation in cancer cells is cell-type specific, we investigated whether glycogen synthase kinase-3beta (GSK-3beta) activation is involved in hypoxia-induced gastric tumor promotion. Stable gastric cancer cell lines (SNU-638, SNU-484, MKN1, and MKN45) were cultured under hypoxic conditions. Cells overexpressing wild-type GSK-3beta (WT-GSK-3beta) or kinase dead mutant of GSK-3beta (KD-GSK-3beta) were generated and used for cell culture and animal studies. In cell culture experiments, hypoxia decreased GSK-3beta activation in gastric cancer cells. Cell viability and the expressions of HIF 1alpha protein and VEGF mRNA in gastric cancer cells were higher in KD-GSK-3beta transfectants than in WT-GSK-3beta transfectants under hypoxic conditions, but not under normoxic conditions. Gastric cancer xenografts showed that tumor growth, microvessel area, HIF-1alpha activation, and VEGF expression were higher in KD-GSK-3beta tumors than in WT-GSK-3beta tumors in vivo. In addition, the expression of hypoxia-induced HIF-1alpha protein was regulated by GSK-3beta at the translational level. Our data suggest that GSK-3beta is involved in hypoxic adaptation of gastric cancer cells as an inhibitory upstream regulator of the HIF 1alpha/VEGF signaling pathway. PMID- 27365054 TI - Comparison of norovirus genogroup I, II and IV seroprevalence among children in the Netherlands, 1963, 1983 and 2006. AB - Noroviruses are a major cause of acute gastroenteritis worldwide and are a genetically diverse group of viruses. Since 2002, an increasing number of norovirus outbreaks have been reported globally, but it is not clear whether this increase has been caused by a higher awareness or reflects the emergence of new genogroup II genotype 4 (GII.4) variants. The hypothesis that norovirus prevalence has increased post-2002 and is related to the emergence of GII.4 is tested in this study. Sera collected from children aged <5 years of three Dutch cross-sectional population based cohorts in 1963, 1983 and 2006/2007 (n=143, n=130 and n=376, respectively) were tested for specific serum IgG by protein array using antigens to GII.4 and a range of other antigens representing norovirus GI, GII and GIV genotypes. The protein array was validated by paired sera of norovirus infected patients and supernatants of B-cell cultures with single epitope specificity. Evidence for norovirus infection was found to be common among Dutch children in each cohort, but the prevalence towards different genotypes changed over time. At the genogroup level, GI seroprevalence decreased significantly between 1963 and 2006/2007, while a significant increase of GII and, in particular, specific antibodies of the genotype GII.4 was detected in the 2006/2007 cohort. There were no children with only GII.4 antibodies in the 1963 cohort. This study shows that the high GII.4 norovirus incidence in very young children is a recent phenomenon. These findings are of importance for vaccine development and trials that are currently focusing mostly on GII.4 viruses. PMID- 27365056 TI - Preparing tomorrow's behavioral medicine scientists and practitioners: a survey of future directions for education and training. AB - Behavioral medicine training is due for an overhaul given the rapid evolution of the field, including a tight funding climate, changing job prospects, and new research and industry collaborations. The purpose of the present study was to collect responses from trainee and practicing members of a multidisciplinary professional society about their perceptions of behavioral medicine training and their suggestions for changes to training for future behavioral medicine scientists and practitioners. A total of 162 faculty and 110 students (total n = 272) completed a web-based survey on strengths of their current training programs and ideas for changes. Using a mixed-methods approach, the survey findings are used to highlight seven key areas for improved preparation of the next generation of behavioral medicine scientists and practitioners, which are grant writing, interdisciplinary teamwork, advanced statistics and methods, evolving research program, publishable products from coursework, evolution and use of theory, and non-traditional career paths. PMID- 27365057 TI - [Echographic Examination for Leg Vein Thromboembolism in Thoracic Surgery]. AB - Echographic examination for leg vein thromboembolism was carried out in 123 patients scheduled for thoracic surgery. Preventive measures for thromboembolism were conducted after the risk assessment. Echography was done after surgery in 72 cases, most of which were cases of lung malignant tumors, and thromboembolism was detected in 4 cases. Thus, the incidence rate of venous thromboembolism was 5.6%( 4/72). There was no patients who developed pulmonary thromboembolism during the examination period, suggesting reasonable risk assessment and preventive measures in our procedure. PMID- 27365058 TI - [Clinical Study of Nine Surgical Cases of Thymic Carcinoma]. AB - Several reports are available on the effectiveness of multimodal therapies, such as chemotherapy and radiotherapy before and after surgery, in addition to surgical resection, as the treatment for thymic carcinoma. However, the sensitivity of each treatment modality varies according to the histological subtype of the carcinoma. Nine patients with thymic carcinoma treated at our hospital were reviewed retrospectively for staging( based on Masaoka's classification), histological findings, surgical method, preoperative and postoperative adjuvant therapy, and prognosis. Differences in the prognosis and treatment response of same-stage thymic carcinomas may be attributable to a difference in histological subtype. The choice of treatment may depend on the histological subtype. PMID- 27365059 TI - [Complete Resection of Non-seminomatous Germ Cell Tumor with Plastron Approach]. AB - A 17-year-old man was admitted to our hospital for the abnormal chest shadow. Chest computed tomography(CT) demonstrated mediastinal tumor, measuring 13 cm in diameter with high serum level of alpha fetoprotein (AFP) and human chorionic gonadotropin (hCG). The lesions were diagnosed as mixed germ cell tumors including a non-seminomatous malignant component by CT guided needle biopsy. After 5 courses of chemotherapy, the serum AFP and hCG were decreased almost normal level but the tumor size was not changed. Because it seemed to be difficult to get sufficient operating field with standard median sternotomy and patient wanted to treat funnel chest, we selected tumor resection with plastron approach. The tumor was completely resected with a good operation field by this procedure. PMID- 27365060 TI - [Ventricular Septal Perforation after Inferior Myocardial Infarction]. AB - We report a rare case of ventricular septal perforation (VSP) after inferior myocardial infarction. Surgical repair of VSP after inferior infarction is technically difficult because of its anatomical location. An 81-year-old female presented with dyspnea on the 8th day after percutaneous coronary intervention for acute inferior myocardial infarction. Echocardiography revealed a ventricular septal perforation. Urgent operation was performed. There was a VSP around the base of the ventricular septum. The myocardial infarction extended to the adjacent muscle of the mitral valve annulus. Two bovine pericardial patches were used in the left ventricular cavity. The patches were sewn on the mitral valve annulus which was the only normal tissue in the region. The 1st patch was used to close the VSP directly, and the 2nd patch was sutured to the normal myocardium to exclude the infracted area. No residual shunt flow was observed. The postoperative course was uneventful. PMID- 27365061 TI - [Atrial Septal Defect with Hereditary Deficiency of Antithrombin III]. AB - A 41-year-old female with hereditary deficiency of antithrombin III (ATIII) was diagnosed with atrial septal defect( ASD) and scheduled for the closure of ASD. She had been taking warfarin since she suffered from deep vein thrombosis 10 years ago. Preoperative management of anticoagulation included discontinuation of warfarin, and supplementation of antithrombin with heparin infusion. On the day of operation, antithrombin activity was maintained above 80% by administering antithrombin, and closure of ASD was carried out under standard cardiopulmonary bypass support using heparin. Heparin infusion was continued with antithrombin supplementation until prothrombin time-international normalized ratio(PT-INR) recovered to around 2.5 with warfarin. Her intra-and postoperative courses did not show any thromboembolic events, and she was discharged 20 days after the surgery. PMID- 27365062 TI - [Chest Wall Reconstruction Using Titanium Plates Sandwiched Between Sheets after Resection of Chest Wall Chondrosarcoma]. AB - Extensive chest wall resection carries the risk of difficult reconstruction and surgical complications. We report our experience on chest wall reconstruction using titanium plates for a wide thoracic defect after tumor resection. A 74-year old man was diagnosed with chondrosarcoma of the 6th rib on the right. He needed extensive chest wall resection because of skip lesions on 4th rib noted on operative inspection, leaving a defect measuring 33 * 20 cm. Reconstruction using 5 transverse titanium plates sandwiched between an expanded polytetrafluoroethylene patch and a polypropylene mesh sheet stabilized the chest wall. This reconstruction allowed successful separation from ventilatory support after operation. The postoperative course was uneventful, and he was discharged on postoperative day 20. The advantages of this form of reconstruction over conventional prostheses are rigidity, and stability and usability. PMID- 27365063 TI - [Displaced B1+2 Found at Video Assisted Thoracic Surgery for Lung Cancer of Left Upper Lobe]. AB - We report the case of an 83-year-old woman who presented with an abnormal pulmonary nodule suspected to be lung cancer in the left S3 segment. Bronchoscopy showed that the left main bronchus branched off into the B1+2, B3 plus lingular bronchus, and lower bronchus. Video-assisted thoracic surgery was performed, and the nodule was pathologically diagnosed as a primary lung cancer. Subsequently, left upper lobectomy was performed, and an abnormal bronchus was observed behind the main pulmonary artery. Intraoperative bronchoscopy indicated that the bronchus was the displaced B1+2. The B3 plus lingular bronchus existed at the common place of the upper bronchus. The displaced B1+2 and the other upper bronchus were transected separately. No other abnormalities were observed in the pulmonary arteries, veins, or bronchi. Preoperative examination is the best way to detect this bronchial abnormality;identification with intraoperative bronchoscopy can play a crucial role in determining the perioperative strategy. PMID- 27365064 TI - [Lung Segmentectomy Using Video-assisted Thoracic Surgery for Lung Cancer in a Patient with Situs Inversus Totalis]. AB - The case was 83-year-old man who had complete situs inversus, and was pointed out to have peripheral adenocarcinoma with the size of 1.8 cm at the left upper lobe( S3). Because of severe emphysema and other multiple comorbidities, left S3 segmentectomy with hilar lymph node sampling was performed using video-assisted thoracic surgery (VATS). Preoperatively, the simulation of operation was performed using the 3 dimension computed tomography images of pulmonary arteriovenous and bronchus (3DCTAB). Postoperative course was uneventful. 3DCTAB was thought to be useful in understanding the anatomical location of pulmonary arteriovenous and bronchus directly, and in performing segmentectomy in the case of situs inversus like this. PMID- 27365065 TI - [Esophageal Injury Treated with a Covered Expandable Metallic Stent]. AB - We report a case of iatrogenic esophageal injury treated with a covered expandable metallic stent after thoracoscopic chest drainage. A 70-year-old man who had stricture of the esophagus after endoscopic submucosal dissection underwent balloon dilation. Chest computed tomography revealed esophageal rupture. Initially, continuous intra-esophageal drainage was carried out, however, due to the development of mediastinitis with enlarged abscess around the descending aorta and the left pneumothorax, thoracoscopic chest drainage was performed. Since direct closure was thought to be in appropriate, an intra esophageal approach was chosen and a covered expandable metallic stent was mounted under fluorography on the next day. After the treatment, the patient was able to eat, and was able to discharge 42 days later. Intra-esophageal covered expandable metallic stent can be an alternative treatment for esophageal rupture. PMID- 27365066 TI - [Caseous Calcification of Mitral Valve Annulus;Report of a Case]. AB - We report a case of an 80-year-old female presenting with a mitral valve tumor. Postoperatively, pathologic diagnosis was caseous calcification of the mitral annulus. In surgery, she successfully underwent a mitral valve replacement with a 20 mm mechanical valve. The importance of correctly making a preoperative diagnosis cannot be over-emphasized. Technical discussion on possibility of mitral valve repair and patient-prosthesis mismatch after mitral valve replacement is also made. PMID- 27365067 TI - [Isolated Pulmonary Valve Endocarditis in a Patient with Aortic Regurgitation and Patent Foramen Ovale;Report of a Case]. AB - Isolated pulmonary valve endocarditis is an extremely rare clinical condition. Here, we report a case of pulmonary valve endocarditis caused by methicillin resistant Staphylococcus aureus (MRSA). An 84-year-old man with a history of aortic regurgitation and patent foramen ovale was admitted to our hospital due to fever of unknown origin for 4 weeks' duration. MRSA was detected in his blood cultures. Transthoracic echocardiography demonstrated a mobile vegetation attached to the pulmonary valve, moderate to severe aortic regurgitation, and patent foramen ovale with left-to-right shunt. After 30-days' treatment with vancomycin, gentamicin and rifampicin, he defervesced and blood cultures became negative. At surgery, a large vegetation was still attached to the pulmonary valve, but the leaflets remained with minimum damage. Aortic valve replacement, direct closure of the patent foramen ovale, and simple resection of the vegetation were performed. The postoperative course was uneventful. PMID- 27365068 TI - [Treatment of Right Atrial Myxoma Complicated with Pulmonary Embolism;Report of a Case]. AB - Myxomas are account for approximately half of primary cardiac tumors, 75% of which originate in the left atrium. We report a case of a right atrial myxoma complicated with bilateral pulmonary embolism. A 54-year-old woman was admitted to the hospital with a complaint of dyspnea. Echocardiography and computed tomography angiography showed a right atrial tumor and bilateral pulmonary embolism. We performed an emergency surgery to remove both the right atrial tumor and the pulmonary emboli. Histopathologically, the tumor was revealed to be myxoma. The postoperative course was uneventful. She is now doing well without any symptoms. PMID- 27365069 TI - [Coronary Artery Bypass Grafting for In-stent Restenosis Probably Caused by Allergic Response;Report of a Case]. AB - A 58-year-old female presented to our hospital with recurrence of chest pain. She had undergone coronary intervention using biolimus-eluting-stent for total occlusion of the left anterior descending artery(LAD) 3 years before. Since then in-stent restenosis had repeated 4 times in 3 years. In the interim, another everolimus-eluting-stent had been placed on the same lesion. The contact metal allergic patch test revealed the existence of allergic response to nickel and cobalt which were the structural components of these stents. She underwent off pump coronary artery bypass grafting, and these stents were removed. The invasions of macrophages and eosinophils around the stent-s were pathologically proven. One year after surgery she is doing well without angina or allergic symptom. These observations suggested the allergic reaction of the coronary artery against the stents. PMID- 27365070 TI - [Coronary Embolism Probably Caused by Surgical Glue after Operation for Acute Aortic Dissection;Report of a Case]. AB - A 70-year-old female underwent an emergency replacement of the ascending aorta for acute aortic dissection. We used surgical adhesive BioGlue and teflon felt strips to reinforce the dissected aortic wall. On the 5th post operative day, electrocardiogram showed ischemic inverted T wave and the serum creatine phosphokinase level elevated without any symptoms such as chest pain or low blood pressure. By coronary angiography, severe stenosis was detected of the left descending coronary artery, and percutaneous coronary intervention was performed. Intravascular ultrasound images revealed that no atherosclerotic components were present in the embolic materials. As a result of in vitro examination, that material was probably a fragment of the BioGlue. The patient was discharged on foot 23 days after surgery. PMID- 27365071 TI - [Myxoma Originating from the Tricuspid Annulus Requiring Annular Reconstruction and Valve Replacement;Report of a Case]. AB - A 66-year-old woman who had had coughing and worsening dyspnea for 3 weeks was admitted to our hospital. Echocardiography showed a solid round mass (72*49 mm in diameter) attached to the tricuspid septal annulus with a short stalk. A right atrial myxoma was suspected and operation was performed under cardiopulmonary bypass after heart failure symptoms subsided. The tumor was extirpated along with the tricuspid valve annulus. We performed reconstruction of the tricuspid annulus, tricuspid valve replacement with a bioprosthetic valve and pacemaker implantation. The histopathologic diagnosis was myxoma. The postoperative course was uneventful, and no recurrence has been noted for 1 year after surgery. PMID- 27365072 TI - [Spindle Cell Sarcoma Originated in the Anterior Mediastinum;Report of a Case]. AB - An anterior mediastinal sarcoma is a very rare type of mediastinal tumor. A 45 year-old female visited our hospital with swelling in the right anterior chest wall. Radiographically, the tumor was found to originate from the thymus and to infiltrate to the major pectoral muscle through the 1st intercostal space. Positron emission tomography revealed fluorodeoxyglucose accumulation at a standardized uptake maximum value of 16.1. Percutaneous needle biopsy showed the pathological findings of sarcoma. The tumor was resected along with the thymus and chest wall tissues including the right hemi-manubrium of the sternum, clavicle head, 1st and second ribs, and major pectoral muscle. After 4 months, tumor relapse occurred at the site of needle biopsy and additional resection was performed. At 10 months after the 2nd surgery, the patient was free from disease. From histologic and immunohistochemical findings, the tumor was diagnosed as spindle cell sarcoma. PMID- 27365073 TI - [Left Lower Lobectomy for an Elderly Patient with Anomalous Systemic Arterial Supply to the Basal Segment of the Left Lung;Report of a Case]. AB - A 76-year-old man was referred to our department for an abnormal shadow on a chest X-ray. Computed tomography showed an aberrant artery arising from the descending thoracic aorta to the basal segment of the left lung. The aberrant artery was dilated and tortuous, and its wall had remarkable calcifications. Bronchial branching to the basal segment of the left lung were normal. The diagnosis of anomalous systemic arterial supply to normal basal segment was established, and division of the aberrant artery and left lower lobectomy were performed successfully. His postoperative course was uneventful, and he was discharged on the 14th postoperative day. We describe herein a rare case of the elderly patient surgically treated for this disease along with a brief review of the literatures. PMID- 27365074 TI - [Venous Thromboembolism during the Cisplatin-based Adjuvant Chemotherapy;Report of a Case]. AB - We report a case of venous thromboembolism during the cisplatin-based adjuvant chemotherapy. A 49-year-old woman who was undergone left lower lobectomy for the lung cancer received adjuvant chemotherapy of cisplatin + vinorelbine ditartrate regimen. On day 11 after starting the chemotherapy, she presented a left lower leg pain and readmitted. Computed tomography revealed a deep venous thrombosis of the left lower leg and peripheral pulmonary embolism. The symptom and thromboembolism were successfully treated by anticoagulant drug and thrombolytic therapy. Although cisplatin-based chemotherapy is a risk factor of venous thromboembolism in patients with advanced malignancy, it should be also recognized as a complication of the adjuvant chemotherapy after surgery. PMID- 27365076 TI - Reply to Chiappetta et al. PMID- 27365075 TI - Frequency of RNF213 p.R4810K, a susceptibility variant for moyamoya disease, and health characteristics of carriers in the Japanese population. AB - OBJECTIVES: RNF213 p.R4810K is a founder polymorphism that confers genetic susceptibility to moyamoya disease in East Asia. Only a few studies have investigated the symptoms and disease histories of RNF213 p.R4810K carriers in Japan. This study investigated the frequency of RNF213 p.R4810K in the general Japanese population and the health characteristics of the carriers. METHODS: Through a health-promotion campaign in the city of Uji, Japan, 519 subjects (120 males and 399 females) of the general Japanese population were genotyped for RNF213 p.R4810K and interviewed to determine health characteristics. RESULTS: Nine RNF213 p.R4810K heterozygous carriers (GA genotype) and no RNF213 p.R4810K homozygous carriers (AA genotype) were found among the 519 individuals. The estimates of the genotypes and allele frequencies for RNF213 p.R4810K were 1.73 and 0.87 %, respectively. There were no obvious differences in age, gender ratio, body mass index, hypertension, dyslipidemia, diabetes, kidney disease, liver disease, heart disease, or drinking or smoking habits between carriers and non carriers. Interestingly, one patient with moyamoya disease was found among the nine RNF213 p.R4810K carriers. CONCLUSIONS: This study showed the genotypes and allele frequencies of RNF213 p.R4810K in the general Japanese population to be similar to results of previous reports. PMID- 27365077 TI - Prevention of surgical site sternal infections in cardiac surgery: a two-centre prospective randomized controlled study. AB - OBJECTIVES: Surgical site infection (SSI) of the sternum is a devastating complication in cardiac surgery. The aim of this prospective randomized controlled two-centre clinical study was to compare the use of a gentamicin collagen sponge (Genta-Coll(r) resorb) and of a cyanoacrylate-based microbial skin sealant (InteguSeal(r)) on the SSI rate of the sternum. METHODS: We analysed data from 996 consecutive patients following isolated coronary artery bypass grafting between 2012 and 2014. The patients were randomized into three groups: standard group (S-group), Genta-Coll group (G-group) and InteguSeal group (I group). The primary study end-point was to analyse the incidence of superficial and deep sternal SSI. The secondary study end-point was to determine independent risk factors for an increased SSI rate. RESULTS: Of the 996 patients investigated, 332 patients were in S-group, 336 patients in G-group and 328 patients in I-group. The mean age was 67.7 +/- 9.4 years, 18.6% were women and the overall SSI rate was 6.2% with 2.2% deep sternal wound infections. SSI rates were 8.3% (S-group), 5.4% (G-group) and 4.9% (I-group) (P 0.16). Multiple regression analysis demonstrated a preoperative body mass index (BMI) of >30 kg/m2 (P 0.047), re-thoracotomy for postoperative bleeding (P < 0.001) and sternum instability (P < 0.001) as independent predictors for an increased SSI rate. CONCLUSIONS: The application of InteguSeal(r) or Genta-Coll(r) resorb had no significant influence on the incidence of the sternal SSI rate in 996 consecutive cardiac surgery patients but demonstrated a trend towards a benefit from using these prophylactic approaches. Multiple regression analysis demonstrated a preoperative BMI of >30 kg/m2, re-thoracotomy for bleeding and sternum instability as independent predictors for an increased sternal SSI rate. PMID- 27365078 TI - What determines the complication rate in high-risk chronic obstructive pulmonary disease patients: surgery or pulmonary function? PMID- 27365080 TI - Axillary evaluation and lymphedema in women with ductal carcinoma in situ. AB - Axillary evaluation in women with ductal carcinoma in situ (DCIS) is increasing; however, this may introduce additional morbidity with unclear benefit. Our objective was to examine the morbidity and mortality associated with axillary evaluation in DCIS. We conducted a retrospective cohort study of 10,504 women aged 65-90 years with DCIS who underwent breast conserving surgery between 2002 and 2012 using SEER-Medicare database. Patients were categorized by receipt of axillary evaluation with either sentinel lymph node biopsy (SLNB) or axillary node dissection (ALND). We determined the incidence of lymphedema treatment as defined by diagnostic and procedural codes, as well as 10-year breast cancer specific and all-cause mortality. 18.3 % of those treated with BCS and 69.4 % of those treated with mastectomy had an axillary evaluation. One year after treatment, 8.2 % of women who had an axillary evaluation developed lymphedema, compared to 5.9 % of those who did not. In a multivariable Cox proportional hazard model, the incidence of lymphedema was higher among those who underwent axillary evaluation (HR 1.22, 95 % CI 1.04-1.45). Overall 10-year breast cancer specific survival was similar between both groups (HR 0.83, 95 % CI 0.40-1.74). Only 44 (0.40 %) women died of breast cancer; receipt of axillary evaluation did not alter overall survival. Axillary evaluation is commonly performed in women with DCIS, especially those undergoing mastectomy. However, women who receive an axillary evaluation have higher rates of lymphedema, without breast cancer specific or overall survival benefit. Efforts should be made to determine the population of women with DCIS who benefit from this procedure. PMID- 27365079 TI - Comparison of Blood Pressure Control Rates Among Recommended Drug Selection Strategies for Initial Therapy of Hypertension. AB - BACKGROUND: Several approaches to initiation of antihypertensive therapy have been suggested. These include thiazide diuretics (TDs) as the first drug in all patients, initial drug selection based on age and race criteria, or therapy selection based on measures of plasma renin activity (PRA). It is uncertain which of these strategies achieves the highest control rate with monotherapy in Stage-I hypertension. We sought to compare control rates among these strategies. METHODS: We used data from the Pharmacogenomic Evaluation of Antihypertensive Responses study (PEAR) to estimate control rates for each strategy: (i) TD for all, (ii) age- and race-based strategy: Hydrochlorothiazide (HCTZ) for all blacks and for whites >=50 years and a renin-angiotensin system inhibitor (atenolol) for whites <50 years) or (iii) a PRA based strategy: HCTZ for suppressed PRA (<0.6ng/ml/h) and atenolol for non-suppressed PRA (>=0.6ng/ml/h) despite age or race. Hypertension was confirmed prior to treatment with HCTZ (148 blacks and 218 whites) or with atenolol (146 blacks and 221 whites). RESULTS: In the overall sample, using clinic blood pressure (BP) response, the renin-based strategy was associated with the greatest control rate (48.9% vs. 40.8% with the age and race based strategy (P = 0.0004) and 31.7% with the TD for all strategy (P < 0.0001)). The findings were similar using home or by 24-hour ambulatory BP responses and within each racial subgroup. CONCLUSIONS: A strategy for selection of initial antihypertensive drug therapy based on PRA was associated with greater BP control rates compared to a thiazide-for-all or an age and race-based strategy. PMID- 27365081 TI - The fate of fibular osteotomies performed during high tibial osteotomy. AB - INTRODUCTION: High tibial osteotomy (HTO) is an important treatment alternative in isolated single compartment knee osteoarthritis. To achieve adequate mechanical axis corrections in the lower extremity fibula is also osteotomized concomitantly. The aim of this study was to compare the union rates of proximal and diaphyseal fibular osteotomies accompanying high tibial osteotomies. METHOD: Sixty-seven knees of sixty-three patients who had undergone HTO were retrospectively evaluated. The patients were grouped according to the level of the fibular osteotomy (FO). In group I, the level of FO was proximal, and in group II, it was at the level of junction of middle and distal third of diaphysis. The union rates of FOs at two different levels were compared. The influence of the presence of displacement at the osteotomy site and apposition between bone ends on union was also evaluated. RESULTS: Fifty-nine of sixty-seven FOs (88.06 %) were united. The union rate of proximal FOs was significantly greater than diaphyseal osteotomies (p < 0.0001); 97.9 % of proximal FOs were united, whereas this ratio was 65 % for the diaphyseal FOs. The presence of displacement at the FO and apposition between bone ends significantly influenced the bony union rate (p values 0.035 and <0.0001, respectively). CONCLUSION: Union rates and nonunion characteristics of FO might differ according to its level, apposition of bone ends, and contact area. The fate of FO might also affect the union of HTO. PMID- 27365082 TI - The value of CT compared to radiographs in the classification and treatment plan of trochanteric fractures. AB - INTRODUCTION: The clinical relevance of classification for trochanteric fractures is limited and little agreement exists on what type of implant should be used. It is unknown whether more advanced radio-diagnostics, such as CT, result in better agreement on the treatment. We assessed the effect of CT on agreement of classification and subsequent treatment for trochanteric fractures. MATERIALS AND METHODS: Eleven observers (five radiologists, four trauma surgeons and two orthopedic residents) assessed 30 radiographs and CTs of trochanteric fractures. Each rating included an assessment according to the AO classification and of the preferred type of implant. The inter-observer agreement of the AO classification and on the choice of implant was calculated. RESULTS: The inter-observer agreement was kappa0.70 (SE 0.03) for radiographic assessment of the main groups of the AO classification and kappa0.68 (SE 0.03) for CT assessment. The agreement on choice of implant was kappa0.63 (SE 0.05) if the choice was made with radiographs and kappa0.69 (SE 0.05) with CTs. Six out of the 13 fractures were classified differently after assessment of the CT. Most corrections in choice of implant occurred for the assessment of A3 fractures. CONCLUSIONS: This study confirmed that trochanteric fractures can be reliably classified on both radiographs and CT, according to the main groups of the AO classification. The implementation of CT for trochanteric fractures does not lead to higher agreement on fracture classification or choice of treatment. Therefore, the clinical relevance of CT for classification of trochanteric fractures seems low. For specific subgroups such as A3 fractures, CT may be of value for adequate fracture classification and subsequent treatment strategies. PMID- 27365083 TI - Genetic Biomarkers to Identify the Risk of Osteonecrosis in Children with Acute Lymphoblastic Leukemia. AB - Osteonecrosis is a disabling complication of treatment for pediatric acute lymphoblastic leukemia, and much effort has been made to predict which patients are prone to develop this disease. Multiple clinical and genetic factors have already been identified as being associated with osteonecrosis; however, a prediction model that combines pretreatment genetic biomarkers and clinical factors has not yet been designed. Such a prediction model can only be developed with continuing international collaborations and research efforts, including large genome-wide association studies. PMID- 27365084 TI - Dedication to Dr. Richard T. Johnson. PMID- 27365085 TI - Vaccinations for Neuroinfectious Disease: A Global Health Priority. AB - Vaccines for neuroinfectious diseases are becoming an ever-increasing global health priority, as neurologic manifestations and sequelae from existing and emerging central nervous system infections account for significant worldwide morbidity and mortality. The prevention of neurotropic infections can be achieved through globally coordinated vaccination campaigns, which have successfully eradicated nonzoonotic agents such as the variola viruses and, hopefully soon, poliovirus. This review discusses vaccines that are currently available or under development for zoonotic flaviviruses and alphaviruses, including Japanese and tick-borne encephalitis, yellow fever, West Nile, dengue, Zika, encephalitic equine viruses, and chikungunya. Also discussed are nonzoonotic agents, including measles and human herpesviruses, as well as select bacterial, fungal, and protozoal pathogens. While therapeutic vaccines will be required to treat a multitude of ongoing infections of the nervous system, the ideal vaccination strategy is pre-exposure vaccination, with the ultimate goals of minimizing disease associated with zoonotic viruses and the total eradication of nonzoonotic agents. PMID- 27365087 TI - Long noncoding RNAs in cell differentiation and pluripotency. AB - Long noncoding RNAs (lncRNAs) were once regarded as nonfunctional by-products of transcription but their effects are now gradually being elucidated. Evidence suggests that lncRNAs play crucial roles in cell biology, especially in regulating gene expression. However, because of the diversity and complexity of their regulatory mechanisms, our knowledge of the function of lncRNAs represents only the tip of the iceberg. Recent studies have shown that lncRNAs are capable of regulating cell differentiation and pluripotency. Thus, we consider it to be an appropriate time to review the progress in understanding the role of lncRNAs in these two biological processes. In this review, the biological characteristics and regulatory mechanisms of lncRNAs at the chromatin remodeling level, transcriptional level and post-transcriptional level are described and recent advances in our comprehension of the role of lncRNAs in cell differentiation and pluripotency are discussed. PMID- 27365086 TI - Italian symptomatic intracranial atherosclerosis study (ISIDE) : A multicenter transcranial ultrasound evaluation. AB - There are currently no data available on the prevalence of symptomatic intracranial atherosclerosis (ICAS) in Italy. The aim of this prospective, multicenter, hospital-based, transcranial ultrasound study was to establish the prevalence of ICAS among patients hospitalized with acute ischemic stroke. At 11 stroke centers across Italy, patients consecutively admitted for their first ever acute ischemic stroke were assessed prospectively over a 24-month period either with transcranial color-coded Doppler sonography (TCCS) or transcranial Doppler (TCD) according to validated criteria. ICAS was diagnosed when there was an evidence of a cerebral infarction in the territory of a >=50 % stenosis detected by TCCS/TCD and confirmed by magnetic resonance angiography or computed tomography angiography. A total of 1134 patients were enrolled, 665 of them (58.6 %) men, with a mean age of 71.2 +/- 13.3 years. ICAS was recorded in 99 patients (8.7 % of the whole sample, 8.9 % among Caucasians), most commonly located in the anterior circulation (63 of 99, 5.5 %). After adjusting for potential confounders, multivariate analysis identified carotid/vertebral >=50 % stenosis [odds ratio (OR) 2.59, 95 % (confidence interval) CI 1.77-6.33; P = 0.02] and hypercholesterolemia (OR 1.38, 95 % CI 1.02-1.89; P = 0.02) as being independently associated with ICAS. ICAS is a surprisingly relevant cause of ischemic stroke in Italy, identified in almost 9 % of first-ever stroke patients. It is more prevalent in the anterior circulation and independently associated with hemodynamically significant cervical vessel atherosclerosis and hypercholesterolemia. These findings support the systematic use of transcranial ultrasound to identify ICAS in patients presenting with acute ischemic stroke and in cases with >=50 % cervical vessel stenoses. PMID- 27365088 TI - Shed proteoglycans in tumor stroma. AB - Cancer cell behavior is not only governed by tumor cell-autonomous properties but also by the surrounding tumor stroma. Cancer-associated fibroblasts, blood vessels, immune cells and the extracellular matrix of the tumor microenvironment have a profound influence on tumor progression. Proteoglycans control various normal and pathological processes, modulating cell proliferation and motility, cell-matrix interactions, immune cell recruitment and angiogenesis. They are major mediators of cancer cell behavior though a dynamic interplay with extracellular matrix components. During cancer progression, their altered expression can promote the activation of several signaling cascades regulating crucial functional properties of cancer cells. Notably, the function of cell surface proteoglycans can be altered by ectodomain shedding, which converts membrane-bound coreceptors into soluble paracrine effector molecules. In this review, we highlight the importance of proteoglycans and their soluble counterparts in cancer progression and the consequences of their interactions with the adjacent stroma. The dynamic interplay among shed proteoglycans and proteolytic enzymes has a significant impact both on tumor cells and their surrounding stroma, with important implications for the diagnosis of this disease and for novel therapeutic approaches. Graphical Abstract Syndecan shedding. The mechanism of shedding involves the proteolytic cleavage of their ectodomain near the plasma membrane by metzincin enzymes, such as metalloproteinases. N acetylglucosamine-alpha-L-iduronic acid/beta-D-glucuronic acid (HS) chains can be additionally cleaved by heparanase. Syndecan core protein can be further processed by intramembrane enzymatic cleavage. Syndecans are in a dynamic interplay with the extracellular matrix and several receptor-tyrosine-kinases (RTKs) and various growth factors, for which they act as co-receptors, thus mediating numerous signaling pathways. PMID- 27365090 TI - Potential drug-drug interactions in medical intensive care unit of a tertiary care hospital in Pakistan. AB - Background Patients admitted to intensive care unit (ICU) present with severe and life-threatening illnesses. Most of them suffer from various comorbidities. They usually receive complex pharmacotherapy with large number of medicines which increase the risk of drug-drug interactions (DDIs). Objective The present report aimed to investigate prevalence and levels of potential DDIs (pDDIs) in medical ICU. Methods Medications profiles of 416 patients were checked for pDDIs using Micromedex Drug-Reax((r)). Prevalence, levels of severity and levels of documentation were reported. Results Of total 416 patients, 310 were exposed to pDDIs (overall prevalence = 74.5 %). Likewise, a prevalence rate of 13.9 % was recorded for contraindicated pDDIs, 52.2 % for major pDDI and 58.4 % for moderate pDDI. This study reported 740 interacting drug pairs that were presented in total 1686 pDDIs. Of 1686 pDDIs, 4.3 % were of contraindicated severity, 33.8 % of major severity and 49.6 % of moderate severity, whereas 45.5 % were of fair scientific evidence and 41.4 % of good scientific evidence. Conclusion In this study, pDDIs were found highly prevalent in ICU patients at a rate of 74.5 %. Most of the pDDIs had moderate severity; however, substantial number of interactions (38.1 %) had major and contraindicated severity. PMID- 27365089 TI - Filamentous influenza viruses. AB - Clinical isolates of influenza virus produce pleomorphic virus particles, including extremely long filamentous virions. In contrast, strains of influenza that have adapted to laboratory growth typically produce only spherical virions. As a result, the filamentous phenotype has been overlooked in most influenza virus research. Recent advances in imaging and improved animal models have highlighted the distinct structure and functional relevance of filamentous virions. In this review we summarize what is currently known about these strikingly elongated virus particles and discuss their possible roles in clinical infections. PMID- 27365091 TI - Clinical and economic impact of pharmacists' intervention in a large volume chemotherapy preparation unit. AB - Background Even though pharmacists have devoted considerable time to ensuring patient safety during the process of preparing and dispensing chemotherapy, only a few studies have evaluated their efforts. Objective To evaluate the clinical and economic impact of pharmacists' interventions in a large volume chemotherapy preparation unit. Setting A 1600-bed tertiary hospital in Seoul, Korea. Method Pharmacist intervention records from May 2012 to April 2013 were retrospectively reviewed. The clinical significance of interventions was rated by one physician and one pharmacist. A cost-benefit analysis was conducted. The benefit from interventions was estimated through both cost avoidance based on the potential to avoid an adverse drug event (ADE) and cost savings related to reducing discarded products. Cost was estimated from the pharmacists' salary corresponding to the time spent in reviewing chemotherapy prescriptions. Main outcome measure Acceptance rate, clinical significance, net cost-benefit, and cost-benefit ratio of pharmacist interventions. Results Among 39,649 cancer chemotherapy prescriptions in 6364 patients, 631 interventions were performed for 435 patients. The acceptance rate was 72.1 %. Most cases of declined interventions were related to dosage adjustment within the range of <10 % of the prescribed dosage. More than half of the interventions were considered as clinically more than "significant" (50.4 %). The cost-benefit analysis showed a clear cost benefit with a net cost-benefit of $116,493 and a cost-benefit ratio of 3.64:1. Conclusion Pharmacists' interventions in a large volume ambulatory-based chemotherapy preparation unit provided a positive economic impact on health care budget and were effective in preventing clinically significant ADEs. PMID- 27365092 TI - Study of warfarin utilization in hospitalized patients: analysis of possible drug interactions. AB - Background Drug-drug interactions in patients taking warfarin may contribute to a higher risk of adverse events. Objective To identify and evaluate the prevalence and characteristics of potential DDIs with warfarin. Methods A cross-sectional study was performed in a Brazilian tertiary hospital. The electronic prescriptions of the patients receiving warfarin between January 2004 and December 2010 were analyzed. Socio-demographic, clinical, and therapeutic variables were collected. Warfarin drug-drug interactions were classified as either risk A, B, C, D, or X according to the Lexi-InteractTM Online database. Results A total of 3048 patients were identified who were prescribed warfarin. Of the 154,161 total drug prescriptions issued, 42,120 (27.3 %) were for warfarin. Evaluation of the prescriptions showed that 63.1 and 0.1 % of patients received concomitant drugs classified as having class D or X risk. It was found that 20,539 (48.7 %) prescriptions had at least one drug with a D or X risk. Patients were prescribed an average of 1.4 (+/-0.4) concomitant medications with a class D or X warfarin-DDI risk, the most frequent being acetylsalicylic acid and amiodarone. Conclusion The results demonstrate a high prevalence of concomitant drug prescriptions with the potential for clinically relevant DDIs with warfarin, the most frequent being acetylsalicylic acid and amiodarone. PMID- 27365093 TI - Medication dispensing errors in Palestinian community pharmacy practice: a formal consensus using the Delphi technique. AB - Background Medication dispensing errors (MDEs) are frequent in community pharmacy practice. A definition of MDEs and scenarios representing MDE situations in Palestinian community pharmacy practice were not previously approached using formal consensus techniques. Objective This study was conducted to achieve consensus on a definition of MDEs and a wide range of scenarios that should or should not be considered as MDEs in Palestinian community pharmacy practice by a panel of community pharmacists. Setting Community pharmacy practice in Palestine. Method This was a descriptive study using the Delphi technique. A panel of fifty community pharmacists was recruited from different geographical locations of the West Bank of Palestine. A three round Delphi technique was followed to achieve consensus on a proposed definition of MDEs and 83 different scenarios representing potential MDEs using a nine-point scale. Main outcome measure Agreement or disagreement of a panel of community pharmacists on a proposed definition of MDEs and a series of scenarios representing potential MDEs. Results In the first Delphi round, views of key contact community pharmacists on MDEs were explored and situations representing potential MDEs were collected. In the second Delphi round, consensus was achieved to accept the proposed definition and to include 49 (59 %) of the 83 proposed scenarios as MDEs. In the third Delphi round, consensus was achieved to include further 13 (15.7 %) scenarios as MDEs, exclude 9 (10.8 %) scenarios and the rest of 12 (14.5 %) scenarios were considered equivocal based on the opinions of the panelists. Conclusion Consensus on a definition of MDEs and scenarios representing MDE situations in Palestinian community pharmacy practice was achieved using a formal consensus technique. The use of consensual definitions and scenarios representing MDE situations in community pharmacy practice might minimize methodological variations and their significant effects on the number and rate of MDEs reported in different studies. PMID- 27365094 TI - Consensus of recommendations guiding comparative effectiveness research methods. AB - PURPOSE: Because of an increasing demand for quality comparative effectiveness research (CER), methods guidance documents have been published, such as those from the Agency for Healthcare Research and Quality (AHRQ) and the Patient Centered Outcomes Research Institute (PCORI). Our objective was to identify CER methods guidance documents and compare them to produce a summary of important recommendations which could serve as a consensus of CER method recommendations. METHODS: We conducted a systematic literature review to identify CER methods guidance documents published through 2014. Identified documents were analyzed for methods guidance recommendations. Individual recommendations were categorized to determine the degree of overlap. RESULTS: We identified nine methods guidance documents, which contained a total of 312 recommendations, 97% of which were present in two or more documents. All nine documents recommended transparency and adaptation for relevant stakeholders in the interpretation and dissemination of results. Other frequently shared CER methods recommendations included: study design and operational definitions should be developed a priori and allow for replication (n = 8 documents); focus on areas with gaps in current clinical knowledge that are relevant to decision-makers (n = 7); validity of measures, instruments, and data should be assessed and discussed (n = 7); outcomes, including benefits and harms, should be clinically meaningful, and objectively measured (n = 7). Assessment for and strategies to minimize bias (n = 6 documents), confounding (n = 6), and heterogeneity (n = 4) were also commonly shared recommendations between documents. CONCLUSIONS: We offer a field-consensus guide based on nine CER methods guidance documents that will aid researchers in designing CER studies and applying CER methods. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27365095 TI - Satisfaction with the Health Care Provider and Regimen Adherence in Minority Youth with Type 1 Diabetes. AB - To assess whether satisfaction with the health-care provider is related to regimen adherence among primarily minority youth with type 1 diabetes. Youth with type 1 diabetes (n = 169; M age = 13.88; 52 % female; 70 % Hispanic) and their parents completed questionnaires that assessed their own satisfaction with the health-care provider and youths' adherence to diabetes self-care behaviors. Higher youth and parent patient-provider relationship satisfaction was associated with higher regimen adherence. Gender affected the relationship between satisfaction and regimen adherence, such that for girls, greater satisfaction was associated with better adherence; this was not the case for boys. Patient satisfaction with the health care provider is important for regimen adherence among primarily minority youth with type 1 diabetes, particularly for girls. Future research might focus on improving youths' relationships with their health care providers as a potential pathway to improve regimen adherence. PMID- 27365097 TI - Fatty acid oxidation is required for the respiration and proliferation of malignant glioma cells. AB - BACKGROUND: Glioma is the most common form of primary malignant brain tumor in adults, with approximately 4 cases per 100 000 people each year. Gliomas, like many tumors, are thought to primarily metabolize glucose for energy production; however, the reliance upon glycolysis has recently been called into question. In this study, we aimed to identify the metabolic fuel requirements of human glioma cells. METHODS: We used database searches and tissue culture resources to evaluate genotype and protein expression, tracked oxygen consumption rates to study metabolic responses to various substrates, performed histochemical techniques and fluorescence-activated cell sorting-based mitotic profiling to study cellular proliferation rates, and employed an animal model of malignant glioma to evaluate a new therapeutic intervention. RESULTS: We observed the presence of enzymes required for fatty acid oxidation within human glioma tissues. In addition, we demonstrated that this metabolic pathway is a major contributor to aerobic respiration in primary-cultured cells isolated from human glioma and grown under serum-free conditions. Moreover, inhibiting fatty acid oxidation reduces proliferative activity in these primary-cultured cells and prolongs survival in a syngeneic mouse model of malignant glioma. CONCLUSIONS: Fatty acid oxidation enzymes are present and active within glioma tissues. Targeting this metabolic pathway reduces energy production and cellular proliferation in glioma cells. The drug etomoxir may provide therapeutic benefit to patients with malignant glioma. In addition, the expression of fatty acid oxidation enzymes may provide prognostic indicators for clinical practice. PMID- 27365096 TI - Key to Opening Kidney for In Vitro-In Vivo Extrapolation Entrance in Health and Disease: Part I: In Vitro Systems and Physiological Data. AB - The programme for the 2015 AAPS Annual Meeting and Exhibition (Orlando, FL; 25-29 October 2015) included a sunrise session presenting an overview of the state-of the-art tools for in vitro-in vivo extrapolation (IVIVE) and mechanistic prediction of renal drug disposition. These concepts are based on approaches developed for prediction of hepatic clearance, with consideration of scaling factors physiologically relevant to kidney and the unique and complex structural organisation of this organ. Physiologically relevant kidney models require a number of parameters for mechanistic description of processes, supported by quantitative information on renal physiology (system parameters) and in vitro/in silico drug-related data. This review expands upon the themes raised during the session and highlights the importance of high quality in vitro drug data generated in appropriate experimental setup and robust system-related information for successful IVIVE of renal drug disposition. The different in vitro systems available for studying renal drug metabolism and transport are summarised and recent developments involving state-of-the-art technologies highlighted. Current gaps and uncertainties associated with system parameters related to human kidney for the development of physiologically based pharmacokinetic (PBPK) model and quantitative prediction of renal drug disposition, excretion, and/or metabolism are identified. PMID- 27365100 TI - How Do Family-Focused Prevention Programs Work? A Review of Mediating Mechanisms Associated with Reductions in Youth Antisocial Behaviors. AB - The development and evaluation of family-focused preventive interventions has grown significantly in recent decades, but the degree to which these interventions produce anticipated improvements in the family environment, and the extent to which such changes are associated with reductions in youth antisocial behaviors (ASB), is unclear. This article seeks to answer these questions by reviewing evidence from tests of mediation conducted in evaluations of family focused interventions. Interventions are drawn from family-focused interventions rated as Model Plus, Model, or Promising on the Blueprints for Healthy Youth Development Web site ( http://www.colorado.edu/cspv/blueprints/ ) based on evidence of their effectiveness in reducing child externalizing behaviors, substance use, and/or delinquency. Of the 19 such interventions listed on Blueprints, seven programs (37 %) were evaluated using mediation analyses which met study criteria. Two-thirds (67 %) of these analyses indicated significant improvements in the targeted family processes for intervention versus control group participants. Over half (62 %) of all tests of mediation were statistically significant and indicated that improvements in the family environment were associated with reductions in ASB. The results support prior theoretical and empirical literature identifying the family as an important context for preventing ASB and promoting healthy youth development. The findings also provide information that can be used to refine current family-focused interventions in order to increase their efficiency and potency, and to develop new interventions in order to expand the number and types of families who can benefit from such services. PMID- 27365099 TI - Service user experiences of REFOCUS: a process evaluation of a pro-recovery complex intervention. AB - PURPOSE: Policy is increasingly focused on implementing a recovery-orientation within mental health services, yet the subjective experience of individuals receiving a pro-recovery intervention is under-studied. The aim of this study was to explore the service user experience of receiving a complex, pro-recovery intervention (REFOCUS), which aimed to encourage the use of recovery-supporting tools and support recovery-promoting relationships. METHODS: Interviews (n = 24) and two focus groups (n = 13) were conducted as part of a process evaluation and included a purposive sample of service users who received the complex, pro recovery intervention within the REFOCUS randomised controlled trial (ISRCTN02507940). Thematic analysis was used to analyse the data. RESULTS: Participants reported that the intervention supported the development of an open and collaborative relationship with staff, with new conversations around values, strengths and goals. This was experienced as hope-inspiring and empowering. However, others described how the recovery tools were used without context, meaning participants were unclear of their purpose and did not see their benefit. During the interviews, some individuals struggled to report any new tasks or conversations occurring during the intervention. CONCLUSION: Recovery-supporting tools can support the development of a recovery-promoting relationship, which can contribute to positive outcomes for individuals. The tools should be used in a collaborative and flexible manner. Information exchanged around values, strengths and goals should be used in care-planning. As some service users struggled to report their experience of the intervention, alternative evaluation approaches need to be considered if the service user experience is to be fully captured. PMID- 27365101 TI - Determining a Child's Best Interests when Parents Refuse Medical Treatment-CAHS v Kiszko & Anor [2016] FCWA 19. PMID- 27365098 TI - The Outcomes of a Limited Resection for Non-Small Cell Lung Cancer Based on Differences in Pathology. AB - OBJECTIVE: A precise preoperative diagnosis of in situ or minimally invasive carcinoma may identify patients who can be treated by limited resection. Although some clinical trials of limited resection for lung cancer have started, it will take a long time before the results will be published. We have already reported a large-scale study of limited resection. We herein report the data for a subclass analysis according to differences in pathology. METHODS: Data from multiple institutions were collected on 1710 patients who had undergone limited resection (segmentectomy or wedge resection) for cT1N0M0 non-small cell carcinoma. The disease-free survival (DFS) and recurrence-free proportion (RFP) were analyzed. Small cell carcinomas and carcinoid tumors were excluded from this analysis. Adenocarcinomas were sub-classified into four groups using two factors, the ratio of consolidation to the tumor diameter (C/T) and the tumor diameter alone. RESULTS: The median patient age was 64 (20-75) years old. The mean maximal diameter of the tumors was 1.5 +/- 0.5 cm. The DFS and RFP at 5 years based on the pathology were 92.2 and 94.7 % in adenocarcinoma (n = 1575), 76.3 and 82.4 % in squamous cell carcinoma (SqCC) (n = 100), and 73.6 and 75.9 % in patients with other tumors (n = 35). The prognosis of adenocarcinoma in both groups A (C/T <=0.25 and tumor diameter <=2.0 cm) and B (C/T <=0.25 and tumor diameter >2.0 cm) was good. In SqCC, only segmentectomy was a favorable prognostic factor. In the groups with other pathologies, large cell carcinomas were worse in prognosis (the both DFS and RFP: 46.3 %). CONCLUSION: Knowing the pathological diagnosis is important to determine the indications for limited resection. Measurement of the tumor diameter and C/T was useful to determine the indications for limited resection for adenocarcinoma. Limited resection for adenocarcinomas is similar with a larger resection, while the technique should be performed with caution in squamous cell carcinoma and other pathologies. PMID- 27365102 TI - Religious Scholars' Attitudes and Views on Ethical Issues Pertaining to Pre Implantation Genetic Diagnosis (PGD) in Malaysia. AB - Pre-Implantation Genetic Diagnosis (PGD) represents the first fusion of genomics and assisted reproduction and the first reproductive technology that allows prospective parents to screen and select the genetic characteristics of their potential offspring. However, for some, the idea that we can intervene in the mechanisms of human existence at such a fundamental level can be, at a minimum, worrying and, at most, repugnant. Religious doctrines particularly are likely to collide with the rapidly advancing capability for science to make such interventions. This paper focuses on opinions and arguments of selected religious scholars regarding ethical issues pertaining to PGD. In-depth interviews were conducted with religious scholars from three different religious organizations in the Klang Valley, Malaysia. Findings showed that Christian scholars are very sceptical of the long-term use of PGD because of its possible effect on the value of humanity and the parent-children relationship. This differs from Islamic scholars, who view PGD as God-given knowledge in medical science to further help humans understand medical genetics. For Buddhist scholars, PGD is considered to be new medical technology that can be used to save lives, avoid suffering, and bring happiness to those who need it. Our results suggest that it is important to include the opinions and views of religious scholars when it comes to new medical technologies such as PGD, as their opinions will have a significant impact on people from various faiths, particularly in a multi-religious country like Malaysia where society places high value on marital relationships and on the traditional concepts of family. PMID- 27365103 TI - Open-Identity Sperm Donation: How Does Offering Donor-Identifying Information Relate to Donor-Conceived Offspring's Wishes and Needs? PMID- 27365104 TI - Relational Capacity: Broadening the Notion of Decision-Making Capacity in Paediatric Healthcare. AB - Problems arise when applying the current procedural conceptualization of decision making capacity to paediatric healthcare: Its emphasis on content-neutrality and rational cognition as well as its implicit assumption that capacity is an ability that resides within a person jeopardizes children's position in decision-making. The purpose of the paper is to challenge this dominant account of capacity and provide an alternative for how capacity should be understood in paediatric care. First, the influence of developmental psychologist Jean Piaget upon the notion of capacity is discussed, followed by an examination of Vygostky's contextualist view on children's development, which emphasizes social interactions and learning for decision-making capacity. In drawing parallels between autonomy and capacity, substantive approaches to relational autonomy are presented that underline the importance of the content of a decision. The authors then provide a relational reconceptualization of capacity that leads the focus away from the individual to include important social others such as parents and physicians. Within this new approach, the outcome of adults' decision-making processes is accepted as a guiding factor for a good decision for the child. If the child makes a choice that is not approved by adults, the new conceptualization emphasizes mutual exchange and engagement by both parties. PMID- 27365105 TI - Genital melanoma: prognosis factors and treatment modality. AB - PURPOSE: Genital melanoma is a rare pathology. We present the experience of two comprehensive cancer centers in Lyon (France) in the management of genital melanoma in order to identify prognostic factors and optimal treatments. METHODS: Between April 1992 and Mars 2014, 16 patients with a primary genital melanoma were referred to our department. Nine patients presented a vaginal melanoma, six vulvar melanomas and only one cervical melanoma. The median dimension of the lesion was 33.7 mm (5-100 mm). The AJCC stage ranged from IB to IIIC. 12 cases were the classic dark-blue flat melanoma and the other 4 cases were an atypical amelanotic tumor. Wide local surgery was performed in nine patients. A radical surgery was performed in six patients. In the large cervical melanoma, radiotherapy was performed as first-line treatment. In all the patients regional lymph node staging was performed. Adjuvant treatment was realized in nine patients. RESULTS: Two patients are alive without recurrence. Only one patient was lost to the first follow-up. The other 13 patients experienced a rapid recurrence. The median disease-free survival and the median overall survival were 11.8 months (2-49 m) and of 30.4 m (11-144 m), respectively. The disease-free survival and overall survival could be linked to a clinical presentation (Breslow thickness and morphology of lesion) associated to the early diagnosis. CONCLUSIONS: In our small series, the most important prognosis factor remains the tumor thickness. These rare lesions should be treated in experienced centers in order to improve their prognostic. PMID- 27365106 TI - Identification of featured biomarkers in breast cancer with microRNA microarray. AB - PURPOSE: We aimed to screen possible biomarkers associated with the molecular mechanism of breast cancer using microRNA (miRNA) microarray. METHODS: The miRNAs expression profile GSE45666 was downloaded from Gene Expression Omnibus database, which included 101 genechips from breast tumor samples and 15 from adjacent breast normal tissue samples. Limma package in R language was used to screen and identify differentially expressed miRNAs (DE-miRNAs) which were classified as up regulated and down-regulated groups. Then, target genes regulated by the two groups of DE-miRNA were predicted, followed by the functional and pathway enrichment analysis using the DAVID system. RESULTS: Totally, 130 DE-miRNAs were screened out, including 59 up-regulated DE-miRNAs and 71 down-regulated DE miRNAs. The functional enrichment indicated that target genes of up- and down regulated DE-miRNA may be most highly associated with positive regulation of gene expression and regulation of cellular metabolic process, respectively. Target genes regulated by the up- and down-regulated DE-miRNAs were mainly enriched in 13 and 14 pathways, respectively, and both were most significant in subcategories in cancer. In addition, we identified three important miRNAs (miR-142-3p, miR-483 5p and miR-483-3p) pivotal for the initiation and progression of this malignant tumor. CONCLUSIONS: MiR-142-3p, miR-483-5p and miR-483-3p are potential key factors for further understanding the molecular mechanism of breast cancer by affecting the normal physiological function of cell. PMID- 27365107 TI - Reporting quality of randomized controlled trial abstracts published in leading laser medicine journals: an assessment using the CONSORT for abstracts guidelines. AB - The objectives of this study were to assess the reporting quality of randomized controlled trial (RCT) abstracts published in leading laser medicine journals and investigate the association between potential predictors and reporting quality. The official online archives of four leading laser medicine journals were hand searched to identify RCTs published in 2014 and 2015. A reporting quality assessment was carried out using the original 16-item CONsolidated Standards Of Reporting Trials (CONSORT) for Abstracts checklist. For each abstract, an overall CONSORT score (OCS) was calculated (score range, 0 to 16). Univariable and multivariable linear regression analyses were performed to identify significant predictors of reporting quality. Chi-square (or Fisher's exact) tests were used to analyze the adequate reporting rate of each quality item by specialty area. A total of 129 RCT abstracts were included and assessed. The mean OCS was 4.5 (standard deviation, 1.3). Only three quality items (interventions, objective, conclusions) were reported adequately in most abstracts (>80 %). No abstract adequately reported results for the primary outcome, source of funding, and status of the trial. In addition, sufficient reporting of participants, outcome in the methods section, randomization, and trial registration was rare (<5 %). According to multivariable linear regression analysis, the specialty area of RCT abstracts was significantly associated with their reporting quality (P = 0.008). The reporting quality of RCT abstracts published in leading laser medicine journals is suboptimal. Joint efforts by authors, editors, and other stakeholders in the field to improve trial abstract reporting are needed. PMID- 27365108 TI - A comparison of incidences of bladder neck contracture of 80- versus 180-W GreenLight laser photoselective vaporization of benign prostatic hyperplasia. AB - Bladder neck contracture (BNC) after GreenLight laser photoselective vaporization (PVP) of benign prostatic hyperplasia is a common complication. In the present study, data of patients received 80 or 180 W PVP were collected. Perioperative parameters, including applied energy, irradiation time, catheter removal time, and hospital stay, were recorded. Postoperative parameters, including maximum urinary flow rate, International Prostate Symptom Score, post-void residual volume, and incidences of BNC, were recorded at 3 and 12 months after operations. Bladder neck tissues were taken at 3 months after operations for immunohistochemical staining and western blot analysis to examine the expressions of collagen I, matrix metalloproteinase-3 (MMP-3), and transforming growth factor beta (TGF-beta). Sample size of patients was calculated with a power of 80 %. Chi square test and one-way analysis of variance were performed as statistical methods. Three hundred twenty-six patients who received potassium titanyl phosphate (KTP) laser and 256 who received X-ray photoelectron spectroscopy (XPS) laser entered into the study. Perioperative parameters were comparable, except for shorter irradiation time in 180 W group (P = 0.032). Postoperative parameters were also similar, except for higher incidence of BNC in 80 W group at 3 months after operations (P = 0.022). Immunohistochemical staining and western blot analysis showed higher expressions of collagen I, MMP-3, and TGF-beta in 80 W group than in 180 W group. In conclusion, 80 W GreenLight laser showed a comparable efficacy with 180-W laser in PVP but showed a higher incidence of BNC in short term, which might be the result of up-regulated fibrotic factors in bladder neck triggered by lasers. PMID- 27365109 TI - Temperature evaluation of dental implant surface irradiated with high-power diode laser. AB - The prevalence of peri-implantitis and the absence of a standard approach for decontamination of the dental implant surface have led to searches for effective therapies. Since the source of diode lasers is portable, has reduced cost, and does not cause damage to the titanium surface of the implant, high-power diode lasers have been used for this purpose. The effect of laser irradiation on the implants is the elevation of the temperature surface. If this elevation exceeds 47 degrees C, the bone tissue is irreversibly damaged, so for a safety therapy, the laser parameters should be controlled. In this study, a diode laser of GaAsAl was used to irradiate titanium dental implants, for powers 1.32 to 2.64 W (real) or 2.00 to 4.00 W (nominal), in continuous/pulsed mode DC/AC, with exposure time of 5/10 s, with/without air flow for cooling. The elevation of the temperature was monitored in real time in two positions: cervical and apical. The best results for decontamination using a 968-nm diode laser were obtained for a power of 1.65 and 1.98 W (real) for 10 s, in DC or AC mode, with an air flow of 2.5 l/min. In our perspective in this article, we determine a suggested approach for decontamination of the dental implant surface using a 968-nm diode laser. PMID- 27365110 TI - Effects of combination of melatonin and laser irradiation on ovarian cancer cells and endothelial lineage viability. AB - The main goal of anti-cancer therapeutic approaches is to induce apoptosis in tumor masses but not in the normal tissues. Nevertheless, the combination of photodynamic irradiation with complementary oncostatic agents contributes to better therapeutic performance. Here, we applied two different cell lines; SKOV3 ovarian carcinoma cells and HUVECs umbilical cord cells as in vitro models to pinpoint whether pharmacological concentration of melatonin in combination with photodynamic therapy induces cell cytotoxicity. The cells were separately treated with various concentrations of melatonin (0 to 10 mM) and photodynamic irradiation alone or in combination. Cells were preliminary exposed to increasing concentrations of melatonin for 24 h and subsequently underwent laser irradiation for 60 s with an output power of 80 mW in continuous mode at 675 nm wavelength and a total light dose of 13.22 J/cm2. Cell viability, apoptosis/necrosis rates, and reactive oxygen species levels as well as heat shock protein 70 expression were monitored after single and combined treatments. A statistical analysis was performed by applying one-way analysis of variance (ANOVA) and post hoc Tukey's test. Combination treatment of both cell lines caused a marked increase in apoptosis/necrosis rate, reactive oxygen species generation, and heat shock protein 70 expression compared to incubation of the cells with each agent alone (p < 0.05). SKOV3 cancer cells expressed higher level of heat shock protein 70 under experimental procedure as compared to HUVECs (p < 0.05). Our results introduce melatonin as a potent stimulus for enhancing the efficacy of laser on induction of apoptosis in tumor cells. PMID- 27365112 TI - Mutations in MSX1, PAX9 and MMP20 genes in Saudi Arabian patients with tooth agenesis. AB - Tooth agenesis in human being is the most common congenital anomaly associated with dental development. Mutations in many genes such as MSH homeobox 1 (MSX1), paired box gene 9 (PAX9), ectodysplasin A (EDA) and EDA receptor (EDAR) have been associated with familial form of this condition. However, in large majority of patients, genetic cause could not be identified. The primary aim of present study was to identify the causative mutation(s) in these genes in Saudi Arabian families diagnosed with non-syndromic form of disease. Direct sequencing of coding regions, including exon-intron boundaries of these genes was carried out. All identified nucleotide variations were also tested to exclude possibility of being rare polymorphisms. The sequence analysis of exons and exon-intronic regions of these genes revealed five new mutations that include four in MSX1, one in PAX9 and one single nucleotide polymorphism (SNP) in majority of the patients in MMP20. One novel mutation in exon 1 of MSX1 gene (5354C > G; A40G) was found in three patients. In addition, another novel mutation was detected in two patients in exon 3 (PAX9) as g.10672A > T which changes asparagine to isoleucine at position 40. These mutations were not found in any of the control subjects. A single SNP in MMP20 genes (g.5066A > C) that changes lysine to threonine at position 18 was found in 10% controls as well. Our results for the first time demonstrates that mutations in MSX1 gene might play an important role in hypodontia cases involving pre-molars and is a risk factor for this ethnic population mainly of Arabs and is first report linking these mutations with tooth agenesis. PMID- 27365111 TI - Altered Expression Pattern of Clock Genes in a Rat Model of Depression. AB - BACKGROUND: Abnormalities in circadian rhythms may be causal factors in development of major depressive disorder. The biology underlying a causal relationship between circadian rhythm disturbances and depression is slowly being unraveled. Although there is no direct evidence of dysregulation of clock gene expression in depressive patients, many studies have reported single-nucleotide polymorphisms in clock genes in these patients. METHODS: In the present study we investigated whether a depression-like state in rats is associated with alternations of the diurnal expression of clock genes. The validated chronic mild stress (CMS) animal model of depression was used to investigate rhythmic expression of three clock genes: period genes 1 and 2 (Per1 and Per2) and Bmal1. Brain and liver tissue was collected from 96 animals after 3.5 weeks of CMS (48 control and 48 depression-like rats) at a 4h sampling interval within 24h. We quantified expression of clock genes on brain sections in the prefrontal cortex, nucleus accumbens, pineal gland, suprachiasmatic nucleus, substantia nigra, amygdala, ventral tegmental area, subfields of the hippocampus, and the lateral habenula using in situ hybridization histochemistry. Expression of clock genes in the liver was monitored by real-time quantitative polymerase chain reaction (PCR). RESULTS: We found that the effect of CMS on clock gene expression was selective and region specific. Per1 exhibits a robust diurnal rhythm in most regions of interest, whereas Bmal1 and in particular Per2 were susceptible to CMS. CONCLUSION: The present results suggest that altered expression of investigated clock genes is likely associated with the induction of a depression like state in the CMS model. PMID- 27365113 TI - Development and persistence of depressive symptoms in adolescents with CHD. AB - Patients with CHD are vulnerable to psychiatric disorders. The present study compared baseline depressive symptoms between adolescents with CHD and community adolescents, and also assessed the development and persistence of depressive symptoms in patients. We examined the implications of persistent depressive symptoms towards quality of life and patient-reported health. In total, 296 adolescents with CHD participated in a four-wave longitudinal study, with 9-month intervals, and completed measures of depressive symptoms - Center for Epidemiologic Studies Depression Scale (CES-D) - at time points one to four and of quality of life - linear analogue scale (LAS) - and patient-reported health - LAS and Pediatric Quality of Life Inventory - at T (time) 4. Information about diagnosis, disease complexity, and previous heart surgery was collected from medical records. At T1, 278 patients were matched 1:1 with community adolescents, based on sex and age. The findings of this study indicate that patients scored significantly lower on depressive symptoms compared with community adolescents. Depressive symptoms in the total patient sample were stable over time and were unrelated to disease complexity. Based on conventional cut-off scores of the CES D, substantial individual differences existed in the extent to which depressive symptoms persisted over time: 12.2% of the patients reported elevated depressive symptoms at minimally three out of the four time points. Especially physical functioning, cardiac symptoms, and patient-reported health at T4 were predicted by persistent depressive symptoms, even when controlling for the level of depressive symptoms at T4. Our findings indicate that those involved in the care of adolescents with CHD should remain vigilant to persistent depressive symptoms and arrange timely referral to mental healthcare services. PMID- 27365115 TI - The effect of a sonographic estimated fetal weight on the risk of cesarean delivery in macrosomic and small for gestational-age infants. AB - OBJECTIVE: To assess the association of a sonographic estimated fetal weight (sonoEFW) with the risk of cesarean delivery in women with macrosomic or small for gestational age (SGA) infants. METHODS: Retrospective cohort of singleton deliveries >24 weeks by one MFM practice from 2005 to 2014. We included all patients who delivered an infant with macrosomia (birth weight >=4000 g) or SGA (birth weight <10th percentile). We compared the risk of cesarean delivery between patients who did and did not have a sonoEFW within four weeks of delivery. Regression analysis was performed to control for any differences in baseline characteristics. RESULTS: In patients with macrosomic infants (n = 352), the risk of cesarean delivery was significantly higher in the sonoEFW group (45.3% versus 17.6%, aOR 2.144, 95% CI: 1.06-4.34). When we restricted the analysis to the subgroup of 265 patients who attempted vaginal delivery, our results were similar (22.3% versus 9.1%, aOR 2.73, 95% CI: 1.15-6.48). In patients with an SGA infant (n = 614), the risk of cesarean delivery was not higher in the sonoEFW group (37.4% versus 24.1%, aOR 1.23, 95% CI: 0.80-2.07), nor in those who attempted vaginal delivery (19.8% versus 13.7%, aOR 1.17, 95% CI: 0.62-2.21). CONCLUSIONS: A sonoEFW prior to delivery is independently associated with cesarean delivery in women with macrosomic infants, but not those with SGA infants. This should be considered when deciding to obtain a sonoEFW at the end of pregnancy, particularly if not for an accepted indication. PMID- 27365116 TI - Whole genome microarray data of chronic wound debridement prior to application of dermal skin substitutes. AB - Clinical consensus is that debridement is necessary for successful application of dermal skin substitutes (DSS) to chronic wounds. The aim here was to identify commonly expressed genes associated with wound healing in untreated acute wounds and chronic wounds treated with wound debridement followed by DSS. Cutaneous biopsies were taken at two time points from untreated acute and chronic wounds and from chronic wounds treated with DSS following debridement. Microarray analysis identified significant differences (p < 0.05) related to proliferation (HIPK2, LGR4, FGFR1, SRRT), migration (RHOC, PRPF40A, FGFR1), differentiation (TCF4, COL13A1, GNPTAB, HUWE1, FGFR1), angiogenesis (HIPK2, CASP8), extracellular matrix organization (VWA1), and apoptosis (BBC3, HIPK2, KLF11, PSME3, MSFD10, TOP2A, MLH1, CASP8, PDIA3, XAF1) when comparing untreated chronic wounds to chronic wounds treated with DSS, with similar expression levels compared to untreated acute wounds. Chronic wounds treated with debridement followed by DSS resemble untreated acute wounds at a genomic level. These novel findings, albeit with limited clinical specimen numbers, strengthen the recommendation to transform chronic into acute wounds prior to application of DSS. PMID- 27365114 TI - Perturbed proteostasis in autism spectrum disorders. AB - Dynamic changes in synaptic strength rely on de novo protein synthesis and protein degradation by the ubiquitin proteasome system (UPS). Disruption of either of these cellular processes will result in significant impairments in synaptic plasticity and memory formation. Mutations in several genes encoding regulators of mRNA translation and members of the UPS have been associated with an increased risk for the development of autism spectrum disorders. It is possible that these mutations result in a similar imbalance in protein homeostasis (proteostasis) at the synapse. This review will summarize recent work investigating the role of the UPS in synaptic plasticity at glutamatergic synapses, and propose that dysfunctional proteostasis is a common consequence of several genetic mutations linked to autism spectrum disorders. Dynamic changes in synaptic strength rely on de novo protein synthesis and protein degradation by the ubiquitin proteasome system (UPS). Disruption of either of these cellular processes will result in significant impairments in synaptic plasticity and memory formation. Mutations in several genes encoding regulators of mRNA translation (i.e. FMR1) and protein degradation (i.e. UBE3A) have been associated with an increased risk for autism spectrum disorders and intellectual disability (ASD/ID). These mutations similarly disrupt protein homeostasis (proteostasis). Compensatory changes that reset the rate of proteostasis may contribute to the neurological symptoms of ASD/ID. This review summarizes recent work investigating the role of the UPS in synaptic plasticity at glutamatergic synapses, and proposes that dysfunctional proteostasis is a common consequence of several genetic mutations linked to ASD. This article is part of a mini review series: "Synaptic Function and Dysfunction in Brain Diseases". PMID- 27365117 TI - Tumor suppression effect of Solanum nigrum polysaccharide fraction on Breast cancer via immunomodulation. AB - A polysaccharide fraction from Solanum nigrum, SN-ppF3 was shown previously to have an immunomodulatory activity where it could possibly be used to enhance the host immune response in fighting cancer. The non-toxic SN-ppF3 was fed orally to breast tumor bearing-mice with concentrations of 250 and 500mg/kg for 10days. During the treatment period, size of the tumor and weight of the mice were monitored. At the end of the treatment, blood, tumor, spleen and thymus were harvested for physiological and immunological analyses. After the treatment, the tumor volume and tumor weight were significantly inhibited by 65% and 40%, respectively. Based on the histological observation, the treatment of SN-ppF3 resulted in the disruption of tumor cells morphology. The increase in infiltrating T cells, NK cells and macrophages were observed in tumor tissues of the treated mice, which partly explained the higher apoptosis tumor cells observed in the treated mice. Moreover, the level of TNF-alpha, IFN-gamma and IL 4 were elevated, while the level of IL-6 was decreased significantly, in serum of the treated mice. These results suggested that tumor suppression mechanisms observed in SN-ppF3-treated mice were most probably due through enhancing the host immune response. PMID- 27365118 TI - GdnHCl-induced unfolding intermediate in the mitochondrial carbonic anhydrase VA. AB - Carbonic anhydrase VA (CAVA) is a mitochondrial enzyme belonging to the alpha family of CAs, which is involved in several physiological processes including ureagenesis, lipogenesis, gluconeogenesis and neuronal transmission. Here, we have tried to understand the folding mechanism of CAVA using guanidine hydrochloride (GdnHCl)-induced denaturation at pH 8.0 and 25 degrees C. The conformational stability was measured from the GdnHCl-induced denaturation study of CAVA monitored by circular dichroism (CD) and fluorescence measurements. On increasing the concentration of GdnHCl up to 5.0, a stable intermediate was observed between the concentrations 3.25M to 3.40M of the denaturant. However, CAVA gets completely denatured at 4.0M GdnHCl. The existence of a stable intermediate state was validated by 1-anilinonaphthalene-8-sulfonic acid (ANS binding) fluorescence and near-UV CD measurements. In silico studies were also performed to analyse the effect of GdnHCl on the structure and stability of CAVA under explicit conditions. Molecular dynamics simulations for 40ns were carried out and a well-defined correlation was established for both in vitro and in silico studies. PMID- 27365119 TI - The anti-diabetic activity of oat beta-d-glucan in streptozotocin-nicotinamide induced diabetic mice. AB - This study was initiated to investigate the mechanism by which oat beta-d-glucan (OBG) can control blood sugar levels and improve hepatogenic glycometabolism in streptozotocin-nicotinamide induced mice. After administration of different concentrations and molecular weights of beta-d-glucan by oral gavage for 28 days, the body weight, fasting blood glucose, serum insulin, hepatic glycogen, glucose kinase and glucose-6-phosphatase activity of the diabetic mice were measured. In comparison with a negative control group (saline), beta-d-glucan, especially medium or high doses of high-molecular-weight beta-d-glucan, had a strong hypoglycaemic effect in streptozotocin-nicotinamide-induced mice. The mechanism of this effect may be associated with the high viscosity of the solution, an increase in insulin secretion, a decline in insulin resistance, and especially an improvement in hepatogenic glycometabolism. Moreover, beta-d-glucan also markedly repaired and improved the integrity of pancreatic islet beta-cell and tissue structures. PMID- 27365120 TI - Hydrophobic starch nanocrystals preparations through crosslinking modification using citric acid. AB - Biodegradable starch nanocrystals prepared by an acid treatment process were modified through crosslinking modification using citric acid as reactant by a dry reaction method. The occurrence of crosslinking modification was evaluated by Fourier transform infrared spectroscopy and swelling degree. X-ray diffraction, wettability tests and contact angle measurements were used to characterize the modified starch nanocrystals. It was found that the crosslinked starch nanocrystals displayed a higher affinity for low polar solvents such as dichloromethane. The surface of starch nanocrystals became more roughness after crosslinking modification with citric acid and the size decreased as revealed by scanning electron microscopy and dynamic light scattering results. XRD analysis showed that the crystalline structure of starch nanocrystals was basically not changed after the crosslinking modification with shorter heating time. The resulting hydrophobic starch nanocrystals are versatile precursors to the development of nanocomposites. PMID- 27365121 TI - Cross-linked enzyme aggregates (CLEAs) of Pencilluim notatum lipase enzyme with improved activity, stability and reusability characteristics. AB - Cross-linked enzyme aggregates (CLEAs) are considered as an effective tool for the immobilization of enzyme. In this study, Pencillium notatum lipase (PNL) was immobilized as carrier free cross-linked enzyme aggregates using glutaraldehyde (GLA) and Ethylene glycol-bis [succinic acid N-hydroxysuccinimide] (EG-NHS) as cross-linking agents. The optimal conditions for the synthesis of an efficient lipase CLEAs such as precipitant type, the nature and amount of cross-linking reagent, and cross-linking time were optimized. The recovered activities of CLEAs were considerably dependent on the concentration of GLA; however, the activity recovery was not severely affected by EG-NHS as a mild cross-linker. The EG-NHS aggregates displayed superior hydrolytic (52.08+/-2.52%) and esterification (64.42%) activities as compared to GLA aggregates which showed 23.8+/-1.86 and 34.54% of hydrolytic and esterification activity, respectively. Morphological analysis by fluorescence and scanning electron microscope revealed that EG-NHS aggregates were smaller in size with larger surface area compared to GLA aggregates. The pH optima of both types of CLEAs were displaced to slightly alkaline region and higher temperature as compared to native enzyme. Highest enzyme activity of CLEAs was achieved at the pH of 9.0 and 42 degrees C temperature. Moreover, a significant improvement in the thermal resistance was also recorded after immobilization. After ten reusability cycles in aqueous medium, GLA and EG-NHS cross-linked lipase CLEAs preserved 63.62% and 70.9% of their original activities, respectively. The results suggest that this novel CLEA lipase is potentially usable in many industrial applications. PMID- 27365122 TI - Kaposiform haemangioendothelioma of the head and neck. AB - BACKGROUND: Kaposiform haemangioendothelioma (KHE) is a tumor of intermediate malignant potential derived from vascular endothelial cells. Due to rarity of head neck KHE (HN-KHE) this comprehensive review aims to compile, analyze and present details to develop a consensus and augment available literature on HN KHE. MATERIALS AND METHODS: A comprehensive literature search was performed on PUBMED/MEDLINE, EMBASE, CINAHL and Science Citation Index for HN-KHE using MeSH words. Statistical analysis was performed using a variety of tests. RESULTS: Common sites of involvement were neck 41.5%, face and scalp 32.0% and tympanomastoid region in 13.2% patients. Kasabach-Merritt phenomenon was seen in 58.5% patients. Surgical excision was performed in 37.7% patients while 39.6% patients underwent medical management/chemotherapy (CT). Significantly better disease free survival (DFS) was seen in patients undergoing surgical excision vs. CT (p=0.001), without recurrence vs. with recurrence (p=0.001) and those presenting within 0-1year of life vs. 1-5 years (p=0.021). CONCLUSION: Recurrence and metastasis were seen in 35.8% and 20.0% patients respectively. Complete surgical excision with clear margins remains the treatment of choice. PMID- 27365125 TI - A near-Infrared Fluorescent Chemodosimeter for Ratiometric Detecting Fluoride Based on Desilylation Reaction. AB - A new chemodosimeter based on dicyanomethylene-4H-chromene chromophore (probe 1) was developed as a ratiometric fluorescent probe in near-infrared range for F(-) with good selectivity in acetonitrile. Probe 1 could be used to directly visualize F(-) by the naked eye and showed more than 621-fold fluorescence enhancement at 715 nm upon reaction with F(-) upon excitation at 625 nm. The recognition of probe 1 to fluoride was featured by F(-)-induced red-shifts of both absorption (185 nm) and fluorescence peaks (132 nm) based on internal charge transfer (ICT) in acetonitrile. The desilylation reaction of 1 by F(-) was proposed for its dual absorption and emission ratiometric detection of fluoride. PMID- 27365123 TI - Adaptive regulation of the brain's antioxidant defences by neurons and astrocytes. AB - The human brain generally remains structurally and functionally sound for many decades, despite the post-mitotic and non-regenerative nature of neurons. This is testament to the brain's profound capacity for homeostasis: both neurons and glia have in-built mechanisms that enable them to mount adaptive or protective responses to potentially challenging situations, ensuring that cellular viability and functionality is maintained. The high and variable metabolic and mitochondrial activity of neurons places several demands on the brain, including the task of neutralizing the associated reactive oxygen species (ROS) produced, to limit the accumulation of oxidative damage. Astrocytes play a key role in providing antioxidant support to nearby neurons, and redox regulation of the astrocytic Nrf2 pathway represents a powerful homeostatic regulator of the large cohort of Nrf2-regulated antioxidant genes that they express. In contrast, the Nrf2 pathway is weak in neurons, robbing them of this particular homeostatic device. However, many neuronal antioxidant genes are controlled by synaptic activity, enabling activity-dependent increases in ROS production to be offset by enhanced antioxidant capacity of both glutathione and thioredoxin-peroxiredoxin systems. These distinct homeostatic mechanisms in neurons and astrocytes together combine to promote neuronal resistance to oxidative insults. Future investigations into signaling between distinct cell types within the neuro-glial unit are likely to uncover further mechanisms underlying redox homeostasis in the brain. PMID- 27365124 TI - Multiple Locus Variable number of tandem repeat Analysis: A molecular genotyping tool for Paenibacillus larvae. AB - American Foulbrood, caused by Paenibacillus larvae, is the most severe bacterial disease of honey bees (Apis mellifera). To perform genotyping of P. larvae in an epidemiological context, there is a need of a fast and cheap method with a high resolution. Here, we propose Multiple Locus Variable number of tandem repeat Analysis (MLVA). MLVA has been used for typing a collection of 209 P. larvae strains from which 23 different MLVA types could be identified. Moreover, the developed methodology not only permits the identification of the four Enterobacterial Repetitive Intergenic Consensus (ERIC) genotypes, but allows also a discriminatory subdivision of the most dominant ERIC type I and ERIC type II genotypes. A biogeographical study has been conducted showing a significant correlation between MLVA genotype and the geographical region where it was isolated. PMID- 27365126 TI - 2,6-Bis(2-Benzimidazolyl)Pyridine Fluorescent Red-Shifted Sensor for Recognition of Zinc(II) and a Calorimetric Sensor for Iron Ions. AB - The ability of 2,6-bis(2-benzimidazolyl)pyridine (bbp) as an optical sensor was studied by fluorescence spectroscopy, colorimetric and UV-visible techniques. The fluorescence spectra of bbp demonstrated a red-shifted upon addition of Zn(2+) ion, whereas rest of the cations did not induce any shift. Selectivity of the sensor was examined toward Zn(2+) in the presence of a wide range of cations, as interfering agents, that showed no disruption in its function. In addition, the pH effect was tested on the fluorescence response of bbp; which showed the efficiency of the sensor in a wide pH range. The limit of detection for Zn(2+) was estimated as 2.1 MUM. Furthermore, the colorimetric studies were carried out and the observations showed a color change from colorless to purple by the addition of Fe(2+) ion and from colorless to yellow by the addition of Fe(3+). The UV-visible studies were carried out to confirm the colorimetric observations. The color changes occurred when Fe(2+) and Fe(3+) were added to the sensors solution, respectively. The detection limits were calculated as 2.8 * 10(-7) M and 3.5 * 10(-6) M for Fe(2+) and Fe(3+), respectively. Hence, bbp can be used as a dual mode optical sensor for detection of Zn(2+) by fluorescence and discriminately detection of Fe(2+) and Fe(3+) visually. PMID- 27365127 TI - Exploring the Transition of Human alpha-Synuclein from Native to the Fibrillar State: Insights into the Pathogenesis of Parkinson's Disease. AB - The etiology of Parkinson's disease involves the interplay between the environmental and genetic factors. Here in this study human alpha-synuclein upon exposure to 100 MUM pendimethalin for 12 h in vitro passes through a partially folded state which proceeds to the aggregated state and terminally ends in the fibrillar phase. Variations in the ANS fluorescence intensities led to the detection of intermediate and aggregated states at 6 and 10 h respectively. Far UV CD analysis depicted significant alpha-helical content for intermediate state at 6 h in presence of 100 MUM pendimethalin. Further increasing the incubation time to 12 h resulted in a predominant beta-sheet content which was confirmed to be fibrillar by TEM. Turbidity, Rayleigh scattering analysis, Congo red assay and ThT measurements supported the TEM data i.e. the formation of fibrillar structure of human alpha-synuclein upon 12 h incubation. Thus, our observation could suggest a possible underlying molecular basis for Parkinson's disease. Graphical Abstract Schematic elucidation of the factors involved in the fibrillation of alpha-Synuclein during Parkinson's pathogenesis. PMID- 27365129 TI - Total anomalous systemic venous drainage in an adult. PMID- 27365130 TI - HIT initiative: discussion with the seniors. PMID- 27365131 TI - Response to: 'Interpreting the guidelines for cleaning up after carbapenemase producing organisms: the devil's in the dilution'. PMID- 27365132 TI - Mitochondrial DNA haplogroups may influence Fabry disease phenotype. AB - While the genetic origin of Fabry disease (FD) is well known, it is still unclear why the disease presents a wide heterogeneity of clinical presentation and progression, even within the same family. Emerging observations reveal that mitochondrial impairment and oxidative stress may be implicated in the pathogenesis of FD. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of FD, we have genotyped European mtDNA haplogroups in 77 Italian FD patients and 151 healthy controls. Haplogroups H and I, and haplogroup cluster HV were significantly more frequent in patients than controls. However, no correlation with gender, age of onset, organ involvement was observed. Our study seems to provide some evidence of a contribution of mitochondrial variation in FD pathogenesis, at least in Italy. PMID- 27365133 TI - Aberrant topographical organization of the default mode network underlying the cognitive impairment of remitted late-onset depression. AB - To investigate the alteration of resting-state functional connectivity (FC) and topological organization of the default mode network (DMN), and their contribution to the cognitive impairment in remitted late-onset depression (rLOD) patients. Thirty-three rLOD patients and thirty-one healthy controls underwent clinical and cognitive evaluations as well as resting-state functional magnetic resonance imaging (R-fMRI) scans. The FC networks were constructed by thresholding Pearson correlation metrics of the DMN regions, and their topological properties were analyzed using graph theory-based approaches. Nonparametric permutation tests were further used for group comparisons of topological metrics. Finally, multiple linear regression analyses were performed to examine the relationships between the network measures and cognitive performances. Patients displayed universally decreased FC of DMN and abnormal global topology of the DMN (i.e., increased characteristic path length Lp and reduced global efficiency Eglob) compared with healthy controls. According to the distance-dependent FC results, the long-distance connections were mainly involved in the connectivity between anterior and posterior hubs, and the short-distance connections were primarily located in the frontal lobe. There were significant correlations between the global topology and the episodic memory performance in rLOD patients. In conclusion, the present study indicated that the disrupted topological organization of the DMN might be considered as a potential biomarker of the episodic memory deficits in rLOD patients. PMID- 27365134 TI - Add-on high frequency deep transcranial magnetic stimulation (dTMS) to bilateral prefrontal cortex reduces cocaine craving in patients with cocaine use disorder. AB - INTRODUCTION: Cocaine dependence is a substantial public health problem. The aim of this study is to evaluate the effect of high frequency deep transcranial magnetic stimulation (dTMS) on craving in patients with cocaine use disorder (CUD). METHODS: Seven men (mean age, 48.71 years; standard deviation [SD], 9.45; range 32-60 years) with CUD and no concurrent axis 1 or 2 disorder save nicotine abuse, underwent three sessions of alternate day 20Hz dTMS in 20 trains delivered to the dorsolateral prefrontal cortex (DLPFC) preferentially to the left hemisphere, for 12 sessions spread over one month, added to unchanged prior drug treatment. We used a visual analogue scale (VAS) to measure cocaine craving the week before, each week during, and one month after dTMS treatment. RESULTS: DLPFC stimulation significantly reduced craving over time: within-subjects main effect of time of treatment (ANOVA, F[3,18]=46.154; p<0.001; eta(2)=0.88). The reduction of craving from baseline was significant at two weeks (p<0.001), and four weeks (p<0.001) of treatment, and at the week eight, four weeks after treatment interruption (p=0.003), although the increase of craving was significant from week four and eight (p=0.014). CONCLUSION: dTMS over left DLPFC reduced craving in CUD patients in a small sample that is to be considered preliminary. However, maintenance sessions would be needed to maintain the achieved results. Our findings highlight the potential of noninvasive neuromodulation as a therapeutic tool for cocaine addiction. PMID- 27365135 TI - Kinetic-Based Reactivity for Michael Acceptors: Structural Activity Relationships and Its Relationship to Excess Acute Fish Toxicity. AB - Acute aquatic toxicity is divided into the "physical" mode governed by weak, non covalent interactions and the "chemical" mode governed by covalent reactions. The potency of chemical interactions is typically expected to be greater than that for physical ones. This enhanced potency is called "excess" toxicity. As databases have become complex, substances thought to elicit a chemical mode reveal a lack of excess toxicity. One mechanism where the latter is prevalent is Michael-type addition. A series of alpha-beta-unsaturated substances were evaluated for reactivity. Second order rate constants (k') were calculated (M-1 s 1) and found to vary from >4000 to <0.0003. The electron-withdrawing capacity of the polar group impacts k' values; the sequence is nitro > carbonyl or sulfone ? sulfoxide, nitrile or amide. When the alpha-carbon and/or the beta-carbon of the pi-system are substituted, the k' value is sharply reduced. Excess toxicity is associated with k' values >0.01 (M-1 s-1). PMID- 27365136 TI - Potential for Phytoremediation of PCDD/PCDF-Contaminated Sludge and Sediments Using Cucurbitaceae Plants: A Pilot Study. AB - The current study evaluates the impact of sewage sludge and urban reservoir sediment on changes in total and Toxic Equivalency (TEQ) PCDD/PCDF concentration in soil and phytotoxicity measured using three test species: Lepidium sativum, Sinapis alba, and Sorghum saccharatum, during 5 weeks of Cucurbita pepo L. cv 'Atena Polka' (zucchini) cultivation. 'Atena Polka' was found to reduce total PCDD/PCDF concentration by 37 % in soil amended with sludge and 32 % in soil treated with sediment from an urban reservoir. The TEQ reduction was almost twofold greater: 68 % in soil amended with sludge and 52 % with urban sediment. Addition of sludge increased root growth inhibition of L. sativum, S. alba and S. saccharatum, from 44 % to 90 %. Observed inhibitions were, however, reduced by 'Atena Polka' cultivation, and as high as 32 % promotion in root length was noted. Amendment with urban sediment, in turn, resulted in an initial 1 %-36 % promotion of root growth, while 'Atena Polka' cultivation reduced this positive effect by inhibition as high as 26 %. Results demonstrated positive influence of 'Atena Polka' on the phytotoxicity alleviation and mitigation of total and TEQ PCDD/PCDF concentrations in soil treated with bio-solids from sewage sludge and an urban reservoir. PMID- 27365137 TI - The Presence of Stimulant Drugs in Wastewater from Krakow (Poland): A Snapshot. AB - An analysis of wastewater from Krakow (Poland) for the presence of controlled and uncontrolled stimulant drugs of abuse was performed. Samples were collected from the Plaszow wastewater treatment plant, Krakow, Poland, and prepared by solid phase extraction. The LC-QTOFMS method was applied for identification and quantification of popular stimulants: MDMA, mephedrone, 4-MEC, MDPV and mCPP. Environmental loads of illicit drugs were calculated; the WWTP discharged loads ranging from 3.6 to 6.7 mg day(-1) 1000 inhabitants(-1) of MDMA, 3.6 to 7.1 mg day(-1) 1000 inhabitants(-1) of mephedrone and 4.8 to 5.8 mg day(-1) 1000 inhabitants(-1) of 4-MEC. The results confirmed the growing popularity of new psychoactive substances in Poland. PMID- 27365138 TI - Multivariate analysis of prognostic factors of lymphoblastic lymphomas of the mediastinum. PMID- 27365139 TI - Coexistent adrenal diffuse large B cell lymphoma in a patient with Waldenstrom's macrogloblinemia/lymphoplasmacytic lymphoma. PMID- 27365140 TI - Droplet digital PCR assay for quantifying of CALR mutant allelic burden in myeloproliferative neoplasms. PMID- 27365141 TI - Retrospective evaluation of the MEAM regimen as a conditioning regimen before autologous peripheral blood stem cell transplantation for lymphoma in two centers with different dosing schedules of melphalan. AB - The BEAM regimen consisting of carmustine (BCNU), etoposide, cytarabine, and melphalan (MEL) is widely used before autologous hematopoietic stem cell transplantation (auto-HSCT) for lymphoma. However, intravenous BCNU is not available in Japan, and therefore, ranimustine (MCNU) has been used instead of BCNU (the MEAM regimen). We retrospectively analyzed the outcome of 79 adult patients who underwent auto-HSCT for lymphoma using this regimen in two centers, with 1- and 2-day dosing of MEL, respectively. Three-year overall survival (OS) and progression-free survival (PFS) probabilities were 77.3 and 56.5 % in the entire population and 71.7 and 58.0 % in patients with diffuse large B cell lymphoma. These outcomes were at least equivalent to those with the BEAM regimen. There was no regimen-related pulmonary toxicity. In a multivariate analysis, older age was the only factor that was significantly associated with for OS. In a comparison of the two MEL dosing schedules, while there was no significant differences in either OS or PFS, diarrhea was observed more frequently with 1-day dosing of MEL. In conclusion, the MEAM regimen appeared to be a promising conditioning regimen in auto-HSCT for lymphoma. A large prospective study is warranted to confirm the current findings. PMID- 27365142 TI - Thalidomide-based induction regimens are as effective as bortezomib-based regimens in elderly patients with multiple myeloma with cereblon expression. AB - Cereblon (CRBN) has been identified as a primary target of immunomodulatory drugs and is considered a biomarker for the prediction of outcomes after thalidomide- or lenalidomide-based treatments. In this study, we evaluated CRBN expression in bone marrow (BM) tissue at diagnosis and investigated the relationship between CRBN expression and treatment outcomes after thalidomide- or bortezomib-based front-line therapies in 89 elderly patients with multiple myeloma (MM). CRBN expression at the time of diagnosis was evaluated with immunohistochemical (IHC) staining for myeloma cells in paraffin wax-embedded BM tissue. CRBN-immunostained slides were scored by intensity and diffuseness, and a total score of >6 was defined as CRBN-positive (CRBN(+)). Thirty-eight patients (45.2 %) were CRBN(+). Among patients treated with thalidomide-based regimens, CRBN(+) patients showed a better treatment response than did CRBN-negative patients (35.0 vs. 11.8 % complete response rate, respectively; HR = 4.038, P = 0.137). During a median follow-up of 31.8 months, patients treated with bortezomib-based regimens had a longer time to progression (TTP) than did patients treated with thalidomide-based regimens (15.6 vs. 13.2 months, respectively; P = 0.047), but early mortality occurred frequently in patients treated with bortezomib-based regimens. Additionally, there was no significant difference in survival outcomes between thalidomide- and bortezomib-based regimens in CRBN(+) patients (median TTP, 13.8 vs. 15.6 months, respectively; P = 0.842 and median OS, 39.3 vs. 30.1 months, respectively; P = 0.074). These data suggest that thalidomide-based regimens are as effective as bortezomib-based regimens in elderly patients with MM who are CRBN(+). Thus, CRBN positivity, by IHC staining, may be useful in deciding appropriate treatment options in elderly patients with MM. PMID- 27365143 TI - Low prevalence of fetal-type posterior cerebral artery in patients with basilar tip aneurysms. AB - BACKGROUND: Basilar tip aneurysms (BTA) are multifactorial in origin, with luminal forces playing a major role in their formation. Considering the reduced hemodynamic stress on the basilar apex in the fetal-type posterior cerebral artery (fPCA), we hypothesize that BTA should be less common in patients with this variant. OBJECTIVE: To investigate, in a retrospective case-control study, the frequency of fPCA in patients with and without BTA. MATERIALS AND METHODS: We collected clinical and imaging data from consecutive patients with BTA undergoing catheter angiography between July 2010 and July 2015, and from a randomly selected, age- and sex-matched non-BTA control population from our prospective database. Anatomical variants of the distal basilar artery region were assessed in the two groups and compared using parametric and non-parametric tests. RESULTS: Fifty-nine BTA cases and 337 controls were included. fPCA was present in 3% of patients with BTA and 23% in the control group (p<0.001; OR=0.11, 95% CI 0.03 to 0.48). Basilar tip disposition was cranial in 49% of BTA and 63% of non BTA cases (p=0.04; OR=0.57, 95% CI 0.33 to 0.99); a caudal disposition was found in 24% and 6% of cases, respectively (p<0.001; OR=4.65, 95% CI 2.21 to 9.80). CONCLUSIONS: We found a statistically significant association between the absence of fPCA and BTA. Our findings underline the importance of hemodynamic stress in the formation of intracranial aneurysms, and suggest that fPCA is a protective variant for formation of BTA. PMID- 27365144 TI - How do generic statements impact performance? Evidence for entity beliefs. AB - Generic statements about the abilities of children's social groups (e.g. 'Girls/Boys are good at this game') negatively impact children's performance - even if the statements are favorable towards children's own social groups. We explored the mechanism by which generic language impairs children's performance. Across three studies, our findings suggest that generic statements influence children's performance by creating an entity belief (i.e. a belief that a fixed ability determines performance). Children who were exposed to a generic statement about their social group's ability performed worse than children in control conditions. This effect hurt children's performance even when the person who made the generic statement was no longer present and a new person not privy to the statement replaced them. However, when children heard a generic statement paired with an effort explanation (i.e. 'Girls/Boys are good at this game because they try really hard when they draw') they performed better than children who heard the generic statement with no explanation (i.e. just 'Girls/Boys are good at this game') and children who heard the generic statement paired with a trait explanation (i.e. 'Girls/Boys are good at this game because they are smart and really good at drawing'). This work uncovers when and how generic statements that refer to the ability of one's social group hinder performance, informing the development of practices to improve student motivation and learning. PMID- 27365145 TI - Revisiting the diagnostic criteria of clinical chorioamnionitis in preterm birth. AB - OBJECTIVE: To re-evaluate the utility of the conventional criteria for clinical chorioamnionitis in the prediction of early-onset neonatal sepsis (EONS) in preterm birth. DESIGN: Retrospective cohort study. SETTING: Seoul, Republic of Korea. SAMPLE: A total of 1468 singleton births between 24 and 34 weeks due to preterm labour (n = 713) or preterm prelabour rupture of membranes (n = 755). METHOD: We evaluated three diagnostic categories of clinical chorioamnionitis: Criteria 1, conventional criteria; Criteria 2, combination of any three conventional parameters without prerequisite fever; Criteria 3, Criteria 1 plus positive maternal C-reactive protein and neutrophil left-shift into minor criteria. EONS included proven or suspected sepsis within 7 days following birth. Neonatal morbidity and mortality of EONS were also reviewed. MAIN OUTCOME MEASURES: Diagnostic performance of three combinations. RESULTS: The prevalence of EONS was 13.8%. Among 203 cases of EONS, maternal manifestation of clinical chorioamnionitis by criteria 1 was evident in only one out of seven, indicating 15.3% sensitivity for EONS prediction. However, with application of criteria 2, sensitivity significantly increased to 34.0%, while compromising specificity from 92.3% to 78.7%. Criteria 3 showed similar diagnostic performance compared with criteria 1 (sensitivity 16.7%, specificity 91.6%). Overall, neonatal mortality and neonatal composite morbidity in EONS were 14.9% and 67.8%, respectively, and there was no difference in neonatal morbidity and mortality between neonates whose mothers showed fever as a sign of clinical chorioamnionitis and those whose mothers did not. CONCLUSION: The renouncement of fever as a prerequisite for the criteria of clinical chorioamnionitis could increase sensitivity for the identification of EONS, a serious outcome of preterm birth. TWEETABLE ABSTRACT: The renouncement of fever as an essential can increase sensitivity for prediction of neonatal sepsis. PMID- 27365146 TI - Characteristics of Peripapillary Staphylomas Associated With High Myopia Determined by Swept-Source Optical Coherence Tomography. AB - PURPOSE: To analyze the morphologic features of peripapillary staphylomas associated with high myopia by swept-source optical coherence tomography (OCT). DESIGN: Validity analysis. METHODS: Highly myopic patients (refractive error >8.0 diopters or axial length >26.5 mm) with a peripapillary staphyloma who had undergone swept-source OCT were studied. The non-highly myopic fellow eyes in patients with unilateral high myopia were also studied. The presence of a peripapillary staphyloma was determined by stereoscopic ophthalmoscopic examinations. The OCT features of the peripapillary staphylomas and other peripapillary lesions were evaluated. RESULTS: Twenty-five eyes of 16 patients were studied. Twenty-two eyes were highly myopic and the remaining 3 eyes of the patients with unilateral high myopia were non-highly myopic. A peripapillary staphyloma was seen in the swept-source OCT images as a gently sloping excavation around the optic disc in all 25 eyes. The posterior sclera in the area of a peripapillary staphyloma was observed to bow posteriorly, with the local curvature steeper than the curvature of the adjacent scleral regions. The sclera at the edge of a peripapillary staphyloma appeared to be elevated inward from the surrounding sclera, and the choroid at the staphyloma edge appeared to be compressed and thinned. A peripapillary intrachoroidal cavitation was a frequent complication and was found in 13 eyes with a peripapillary staphyloma (52.5%). CONCLUSIONS: Swept-source OCT can detect the slight changes of the sclera and choroid in the area of a peripapillary staphyloma, and we recommend its use in determining the presence of a peripapillary staphyloma. PMID- 27365147 TI - Internal Hernia Following Laparoscopic Roux-en-Y Gastric Bypass: Prevention and Tips for Intra-operative Management. AB - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is considered the golden standard for bariatric surgery. However, the potential risk for internal hernia after LRYGB remains a significant concern to both patients and surgeons. In addition, patients presenting with abdominal pain after LRYGB warrant careful attention to avoid missing or delaying the diagnosis of internal hernia. The aim of this study was to describe our technique to prevent internal hernia after LRYGB, intra-operative findings, and our management strategies for patients with internal hernia after LRYGB. METHODS: In this video, we review different technical tips and tricks to explore patients with suspected internal hernia after RYGB, how to reduce obstructed small bowel, and effectively close mesenteric defects to prevent internal hernia after LRYGB. RESULTS: A high index of suspicion and evaluation of the CT scan of the patient by an experienced bariatric surgeon is essential to avoid missing cases of internal hernia after LRYGB. In addition, patients presenting with incarcerated small bowel due to an internal hernia are best managed by standing on the left side of the patient with the left arm tucked and starting at the ileocecal valve and running the small bowel backwards towards the ligament of Treitz. Furthermore, patients with bowel obstruction due to internal hernia may need to have a gastrostomy placed at the remnant of the stomach. CONCLUSION: Recurrent abdominal pain is not uncommon after LRYGB. Systematic closure of mesenteric defects, the use of diagnostic laparoscopy, and high index of suspicion are all necessary to avoid delay in diagnosis. PMID- 27365148 TI - How does adenosine control neuronal dysfunction and neurodegeneration? AB - The adenosine modulation system mostly operates through inhibitory A1 (A1 R) and facilitatory A2A receptors (A2A R) in the brain. The activity-dependent release of adenosine acts as a brake of excitatory transmission through A1 R, which are enriched in glutamatergic terminals. Adenosine sharpens salience of information encoding in neuronal circuits: high-frequency stimulation triggers ATP release in the 'activated' synapse, which is locally converted by ecto-nucleotidases into adenosine to selectively activate A2A R; A2A R switch off A1 R and CB1 receptors, bolster glutamate release and NMDA receptors to assist increasing synaptic plasticity in the 'activated' synapse; the parallel engagement of the astrocytic syncytium releases adenosine further inhibiting neighboring synapses, thus sharpening the encoded plastic change. Brain insults trigger a large outflow of adenosine and ATP, as a danger signal. A1 R are a hurdle for damage initiation, but they desensitize upon prolonged activation. However, if the insult is near threshold and/or of short-duration, A1 R trigger preconditioning, which may limit the spread of damage. Brain insults also up-regulate A2A R, probably to bolster adaptive changes, but this heightens brain damage since A2A R blockade affords neuroprotection in models of epilepsy, depression, Alzheimer's, or Parkinson's disease. This initially involves a control of synaptotoxicity by neuronal A2A R, whereas astrocytic and microglia A2A R might control the spread of damage. The A2A R signaling mechanisms are largely unknown since A2A R are pleiotropic, coupling to different G proteins and non-canonical pathways to control the viability of glutamatergic synapses, neuroinflammation, mitochondria function, and cytoskeleton dynamics. Thus, simultaneously bolstering A1 R preconditioning and preventing excessive A2A R function might afford maximal neuroprotection. The main physiological role of the adenosine modulation system is to sharp the salience of information encoding through a combined action of adenosine A2A receptors (A2A R) in the synapse undergoing an alteration of synaptic efficiency with an increased inhibitory action of A1 R in all surrounding synapses. Brain insults trigger an up-regulation of A2A R in an attempt to bolster adaptive plasticity together with adenosine release and A1 R desensitization; this favors synaptotocity (increased A2A R) and decreases the hurdle to undergo degeneration (decreased A1 R). Maximal neuroprotection is expected to result from a combined A2A R blockade and increased A1 R activation. This article is part of a mini review series: "Synaptic Function and Dysfunction in Brain Diseases". PMID- 27365149 TI - Absence of Basal Cell Carcinoma in Irradiated Childhood Cancer Survivors of Black Race: A Report from the St. Jude Lifetime Cohort Study. AB - BACKGROUND: Cancer survivors exposed to therapeutic radiation are at increased risk for basal cell carcinoma (BCC). Despite the notable influence of race on rates of BCC in the general population, the same is not clearly defined in previously irradiated cancer survivors. We investigated the influence of race on the development of BCC in adult survivors of childhood cancer. METHODS: Using a retrospective cohort study, outcomes were collected through June 30, 2015, for 1,746 irradiated childhood cancer survivors participating in the St. Jude Lifetime Cohort Study (SJLIFE), comprising a total of 33,147 person-years of follow-up. Subsequent neoplasms identified in survivors through self-report and prospective clinical assessment were validated by pathology reports. Expected numbers of each type of radiation-associated neoplasm, including BCC, were calculated for irradiated black survivors based on rates in irradiated white survivors, accounting for primary cancer diagnosis, diagnosis year, attained age, and sex. RESULTS: On the basis of the rate of BCC in previously irradiated white survivors, 56.1 BCCs were expected among 237 black survivors, yet none observed. In contrast, the observed-to-expected ratio of non-BCC radiation-associated neoplasms (melanoma, brain, breast, thyroid cancer) was 0.88 (30 observed/34.2 expected, 95% confidence interval, 0.59-1.25). CONCLUSIONS: We identified an unexpected absence of BCC in irradiated black survivors in SJLIFE. We observe a similar absence of BCC in black individuals among two additional cohorts treated with irradiation for childhood cancer. IMPACT: Black survivors are at a substantially reduced or absent risk for BCC from therapeutic radiation for reasons not yet fully understood. Cancer Epidemiol Biomarkers Prev; 25(9); 1356 60. (c)2016 AACR. PMID- 27365150 TI - Pet Ownership and Cancer Risk in the Women's Health Initiative. AB - BACKGROUND: Pet ownership and cancer are both highly prevalent in the United States. Evidence suggests that associations may exist between this potentially modifiable factor and cancer prevention, though studies are sparse. The present report examined whether pet ownership (dog, cat, or bird) is associated with lower risk for total cancer and site-specific obesity-related cancers. METHODS: This was a prospective analysis of 123,560 participants (20,981 dog owners; 19,288 cat owners; 1,338 bird owners; and 81,953 non-pet owners) enrolled in the Women's Health Initiative observational study and clinical trials. Cox proportional hazards models were used to estimate HR and 95% confidence intervals for the association between pet ownership and cancer, adjusted for potential confounders. RESULTS: There were no significant relationships between ownership of a dog, cat, or bird and incidence of cancer overall. When site-specific cancers were examined, no associations were observed after adjustment for multiple comparisons. CONCLUSION: Pet ownership had no association with overall cancer incidence. IMPACT: This is the first large epidemiologic study to date to explore relationships between pet ownership and cancer risk, as well as associated risks for individual cancer types. This study requires replication in other sizable, diverse cohorts. Cancer Epidemiol Biomarkers Prev; 25(9); 1311-6. (c)2016 AACR. PMID- 27365151 TI - Utility of Model-Based Approaches for Informing Dosing Recommendations in Specific Populations: Report From the Public AAPS Workshop. AB - This report summarizes the discussions and recommendations of the workshop titled "Specific Population Drug Dosing Recommendations: Shifting from Clinical Studies to Predict and Confirm," which preceded the 2015 American Association of Pharmaceutical Scientists annual meeting. Participants from the pharmaceutical industry, regulatory agencies (FDA and EMA), and academia discussed the current state, challenges, opportunities, and future direction of utilizing model-based approaches to inform dosing recommendations in specific populations. PMID- 27365152 TI - Network architectures and operating principles: Reply to comments on "Drivers of structural features in gene regulatory networks: From biophysical constraints to biological function". PMID- 27365153 TI - Drivers of structural features in gene regulatory networks: From biophysical constraints to biological function. AB - Living cells can maintain their internal states, react to changing environments, grow, differentiate, divide, etc. All these processes are tightly controlled by what can be called a regulatory program. The logic of the underlying control can sometimes be guessed at by examining the network of influences amongst genetic components. Some associated gene regulatory networks have been studied in prokaryotes and eukaryotes, unveiling various structural features ranging from broad distributions of out-degrees to recurrent "motifs", that is small subgraphs having a specific pattern of interactions. To understand what factors may be driving such structuring, a number of groups have introduced frameworks to model the dynamics of gene regulatory networks. In that context, we review here such in silico approaches and show how selection for phenotypes, i.e., network function, can shape network structure. PMID- 27365154 TI - Reconstructing the past: The late posterior negativity (LPN) in episodic memory studies. AB - The late posterior negativity (LPN) is an ERP effect frequently reported in episodic memory tasks. In 2003, we proposed that both non-mnemonic action monitoring processes and reconstructive mnemonic processes contribute to the LPN. Here, we review more recent studies and provide additional evidence that the LPN reflects dissociable (though not mutually exclusive) mnemonic and non-mnemonic processes. The idea that the LPN is related to the modality-specific reactivation of brain regions activated during encoding is critically evaluated. We suggest that the LPN is modulated by the amount of information actually used to reconstruct prior episodes and in parts mediated by source specifying factors, like the amount and overlap of memory bound attributes. We propose that the LPN reflects domain general mechanisms recruited not just during episodic but also during semantic memory tasks, in particular in situations that require highly specific reconstructive processing or continued evaluation of retrieval outcomes. Finally, we relate these ideas to recent accounts of the role of the parietal cortex in allocating attention for the inspection of memory contents. PMID- 27365155 TI - Molecular detection and characterization of spotted fever group rickettsiae in ticks from Central Italy. AB - The aim of this study was to investigate the presence of rickettsial pathogens in ticks from Central Italy. A total of 113 ticks hailed from Latium and Tuscany regions were identified and tested by PCR to detect gltA, ompA, ompB genes of Rickettsia. Positive amplicons were sequenced and identified at species level. Ticks were analyzed individually or in pools. The percentage of positivity for SFG rickettsiae was 12.4%, expressed as minimum infection rate (MIR) assuming that one tick was positive in each positive pool. Rickettsia aeschlimannii was detected in Hyalomma marginatum, Rickettsia monacensis in Ixodes ricinus and Rickettsia massiliae and Rickettsia conorii in Rhipicephalus sanguineus sensu lato. These findings confirm the circulation of pathogenic rickettsiae in Latium and Tuscany regions. To our knowledge this is the first report of R. massiliae in Latium region. PMID- 27365156 TI - Reverse engineering inhibitory circuits in hippocampal CA3. PMID- 27365157 TI - Local field potentials get funny. PMID- 27365158 TI - Nerve regeneration in the peripheral and central nervous systems. PMID- 27365159 TI - Letter to the Editor. PMID- 27365160 TI - Reply from Peter A. Watterson and Graham M. Nicholson. PMID- 27365161 TI - Limitations of the F-wave test in monitoring spinal motoneurone excitability. PMID- 27365162 TI - Reply from S. C. Gandevia, S. L. Khan and J. L. Taylor. PMID- 27365163 TI - Regulation and Functions of Autophagic Lipolysis. AB - The selective breakdown by autophagy of lipid droplet (LD)-stored lipids, termed lipophagy, is a lysosomal lipolytic pathway that complements the actions of cytosolic neutral lipases. The physiological importance of lipophagy has been demonstrated in multiple mammalian cell types, as well as in lower organisms, and this pathway has many functions in addition to supplying free fatty acids to maintain cellular energy stores. Recent studies have begun to delineate the molecular mechanisms of the selective recognition of LDs by the autophagic machinery, as well as the intricate crosstalk between the different forms of autophagy and neutral lipases. These studies have led to increased interest in the role of lipophagy in both human disease pathogenesis and therapy. PMID- 27365164 TI - Comparison of Capillary and Venous Drug Concentrations After Administration of a Single Dose of Risperidone, Paliperidone, Quetiapine, Olanzapine, or Aripiprazole. AB - Risperidone, paliperidone, quetiapine, olanzapine, and aripiprazole are antipsychotic drugs approved for treating various psychiatric disorders, including schizophrenia. The objective of this randomized, parallel-group, open label study was to compare finger-stick-based capillary with corresponding venous whole-blood and plasma concentrations for these drugs after administration of a single dose to healthy volunteers. All whole-blood and plasma drug concentrations were measured with validated liquid chromatography-tandem mass spectrometry methods. Capillary and venous concentrations (both in plasma and whole blood) were in close agreement, although a time-dependent difference was observed, most obviously for olanzapine and paliperidone, with slightly higher capillary versus venous drug concentrations during the first hours after administering a single dose. The observed difference between capillary and venous plasma drug concentrations is expected not to be relevant in clinical practice, considering the wide window of therapeutic concentrations and the wide range of drug concentrations in the patient population for a given dose. Based on these results, finger-stick-based capillary drug concentrations have been shown to approximate venous drug concentrations. PMID- 27365165 TI - Understanding the structure and function of bacterial expansins: a prerequisite towards practical applications for the bioenergy and agricultural industries. AB - Since the publication of a landmark article on the structure of EXLX1 from Bacillus subtilis in 2011, our knowledge of bacterial expansins has steadily increased and our view and understanding of these enigmatic proteins has advanced with relation to their structure, phylogenetic relationships and substrate interaction, although the molecular basis for their mechanism of action remains to be determined. Lignocellulosic material represents a source of fermentable sugars for the production of biofuels, and cell-wall degrading activities are essential to efficiently release such sugars from their polymeric structures. Because expansins from fungi and bacteria seem to be required to properly colonize or cause disease to plant tissues, and because they share some characteristics with their plant counterparts for loosening the cell wall they have been seen as a promising tool to overcome the recalcitrance of these materials. However, microbial expansins activity is at best, very low compared with plant expansins activity. This revision analyses recent work on bacterial expansins structure, function and biological role, emphasizing our need to focus on their mechanism of action as a means to design better strategies for their use, in both in the energy and agricultural industries. PMID- 27365166 TI - Integrated fabrication-conjugation methods for polymeric and hybrid microparticles for programmable drug delivery and biosensing applications. AB - Functionalized polymeric microparticles possess significant potential for controlled drug delivery and biosensing applications, yet current fabrication techniques face challenges in simple and scalable fabrication and biofunctionalization. For programmable manufacture of biofunctional microparticles in a simple manner, we have developed robust micromolding methods combined with biopolymeric conjugation handles and bioorthogonal click reactions. In this focused minireview, we present detailed methods for our integrated approaches for fabrication of microparticles with controlled 2D and 3D shapes and dimensions toward controlled release, and for biomacromolecular conjugation via strain promoted alkyne-azide cycloaddition (SPAAC) and tetrazine-trans cyclooctene (Tz-TCO) ligation reactions utilizing a potent aminopolysaccharide chitosan as an efficient conjugation handle. We believe that the fabrication conjugation methods reported here from a range of our recent reports illustrate the simple, robust and readily reproducible nature of our approaches to creating multifaceted microparticles in a programmable, cost-efficient and scalable manner toward a wide range of medical and biotechnological application areas. PMID- 27365167 TI - Advances in technology and business potential of new drug delivery systems. PMID- 27365169 TI - Magnetically recoverable catalysts based on mono- or bis-(NHC) complexes of palladium for the Suzuki-Miyaura reaction in aqueous media: two NHC-Pd linkages are better than one. AB - Pre-synthesized mono- and bis(NHC) palladium complexes have been grafted onto magnetic core/shell gamma-Fe2O3/silica particles and tested as catalysts in model Suzuki-Miyaura coupling reactions. The bis(NHC) immobilized complex was found to be a robust catalyst that can operate under mild conditions in aqueous media, even for the activation of chloroarene, whereas the mono(NHC) counterpart rapidly deactivates. Moreover, it can be readily recovered by magnetic separation and reused many times, providing very high productivities, and with so low leaching of palladium that the crude products obtained contain <=10 ppm Pd. PMID- 27365168 TI - External root resorption with the self-ligating Damon system-a retrospective study. AB - BACKGROUND: The aim of this study was to compare the degree of external apical root resorption (EARR) in patients treated with self-ligating Damon appliances and with conventional preadjusted appliances. METHODS: The sample comprised 52 patients, divided into two groups. Group 1 consisted of 25 patients treated with self-ligating Damon appliances, with an initial age of 16.04 years, final age of 18.06 years, and treatment time of 2.02 years. Group 2 consisted of 27 patients, treated with conventional preadjusted appliances, with an initial age of 16.77 years, final age of 18.47 years and treatment time of 1.70 years. The groups were matched regarding the initial and final ages, treatment time, type of malocclusion, and treatment protocol without extractions. Root resorption was evaluated on periapical radiographs of the maxillary and mandibular incisors at the end of orthodontic treatment with the scores of Levander and Malmgren. Intergroup comparisons of root resorption were performed with Mann-Whitney tests. RESULTS: No significant difference in the degree of root resorption between the two groups was found. CONCLUSIONS: Similar degrees of resorption can be expected after non-extraction treatment with Damon self-ligating or conventional preadjusted appliances. PMID- 27365170 TI - The T-type calcium channel antagonist Z944 disrupts prepulse inhibition in both epileptic and non-epileptic rats. AB - The role of T-type calcium channels in brain diseases such as absence epilepsy and neuropathic pain has been studied extensively. However, less is known regarding the involvement of T-type channels in cognition and behavior. Prepulse inhibition (PPI) is a measure of sensorimotor gating which is a basic process whereby the brain filters incoming stimuli to enable appropriate responding in sensory rich environments. The regulation of PPI involves a network of limbic, cortical, striatal, pallidal and pontine brain areas, many of which show high levels of T-type calcium channel expression. Therefore, we tested the effects of blocking T-type calcium channels on PPI with the potent and selective T-type antagonist Z944 (0.3, 1, 3, 10mg/kg; i.p.) in adult Wistar rats and two related strains, the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and Non Epileptic Control (NEC). PPI was tested using a protocol that varied prepulse intensity (3, 6, and 12dB above background) and prepulse-pulse interval (30, 50, 80, 140ms). Z944 decreased startle in the Wistar strain at the highest dose relative to lower doses. Z944 dose-dependently disrupted PPI in the Wistar and GAERS strains with the most potent effect observed with the higher doses. These findings suggest that T-type calcium channels contribute to normal patterns of brain activity that regulate PPI. Given that PPI is disrupted in psychiatric disorders, future experiments that test the specific brain regions involved in the regulation of PPI by T-type calcium channels may help inform therapeutic development for those suffering from sensorimotor gating impairments. PMID- 27365171 TI - Dorsomedial striatum lesions affect adjustment to reward uncertainty, but not to reward devaluation or omission. AB - The dorsomedial striatum (DMS) has been implicated in the acquisition of reward representations, a proposal leading to the hypothesis that it should play a role in situations involving reward loss. We report the results of an experiment in which the effects of DMS excitotoxic lesions were tested in consummatory successive negative contrast (reward devaluation), autoshaping training with partial vs. continuous reinforcement (reward uncertainty), and appetitive extinction (reward omission). Animals with DMS lesions exhibited reduced lever pressing responding, but enhanced goal entries, during partial reinforcement training in autoshaping. However, they showed normal negative contrast, acquisition under continuous reinforcement (CR), appetitive extinction, and response facilitation in early extinction trials. Open-field testing also indicated normal motor behavior. Thus, DMS lesions selectively affected the behavioral adjustment to a situation involving reward uncertainty, producing a behavioral reorganization according to which goal tracking (goal entries) became predominant at the expense of sign tracking (lever pressing). This pattern of results shows that the function of the DMS in situations involving reward loss is not general, but restricted to reward uncertainty. We suggest that a nonassociative, drive-related process induced by reward uncertainty requires normal output from DMS neurons. PMID- 27365172 TI - Sensitivity of the prefrontal GABAergic system to chronic stress in male and female mice: Relevance for sex differences in stress-related disorders. AB - Stress-induced modifications of the prefrontal cortex (PFC) are believed to contribute to the onset of mood disorders, such as depression and anxiety, which are more prevalent in women. In depression, the PFC is hypoactive; however the origin of this hypoactivity remains unclear. Possibly, stress could impact the prefrontal GABAergic inhibitory system that, as a result, impairs the functioning of downstream limbic structures controlling emotions. Preclinical evidence indicates that the female PFC is more sensitive to the effects of stress. These findings suggest that exposure to stress could lead to sex-specific alterations in prefrontal GABAergic signaling, which contribute to sex-specific abnormal functioning of limbic regions. These limbic changes could promote the onset of depressive and anxiety behaviors in a sex-specific manner, providing a possible mechanism mediating sex differences in the clinical presentation of stress related mood disorders. We addressed this hypothesis using a mouse model of stress-induced depressive-like behaviors: the unpredictable chronic mild stress (UCMS) paradigm. We observed changes in prefrontal GABAergic signaling after exposure to UCMS most predominantly in females. Increased parvalbumin (PV) expression and decreased prefrontal neuronal activity were correlated in females with severe emotionality deficit following UCMS, and with altered activity of the amygdala. In males, small changes in emotionality following UCMS were associated with minor changes in prefrontal PV expression, and with hypoactivity of the nucleus accumbens. Our data suggest that prefrontal hypoactivity observed in stress-related mood disorders could result from stress-induced increases in PV expression, particularly in females. This increased vulnerability of the female prefrontal PV system to stress could underlie sex differences in the prevalence and symptomatology of stress-related mood disorders. PMID- 27365173 TI - Imipramine and amitriptyline ameliorate the rotenone model of Parkinson's disease in rats. AB - Amitriptyline (AMI), a commonly prescribed tricyclic antidepressant (TCA) to parkinsonian patients, specifically showed a significant delay in dopaminergic therapy initiation and improvement in motor disability in parkinsonian patients. Moreover, it was recently shown that AMI has neuroprotective properties; however, the mechanisms underlying this effect in Parkinson's disease (PD) are not fully understood. The current study aimed to investigate the possible neuroprotective mechanisms afforded by AMI in the rotenone model of PD and to assess whether another TCA member, imipramine (IMI), shows a corresponding effect. Rats were allocated into seven groups. Four groups were given either saline, dimethyl sulfoxide, AMI or IMI. Three rotenone groups were either untreated or treated with AMI or IMI. Rats receiving rotenone exhibited motor impairment in open field and rotarod tests. Additionally, immunohistochemical examination revealed dopaminergic neuronal damage in substantia nigra. Besides, striatal monoamines and brain derived neurotrophic factor levels were declined. Furthermore, oxidative stress, microglial activation and inflammation were evident in the striata. Pretreatment of rotenone groups with AMI or IMI prevented rotenone induced neuronal degeneration and increased striatal dopamine level with motor recovery. These effects were accompanied by restoring striatal monoamines and brain-derived neurotrophic factor levels, as well as reducing oxidative damage, microglial activation and expression of proinflammatory cytokines and inducible nitric oxide synthase. The present results suggest that modulation of noradrenaline and serotonin levels, up-regulation of neurotrophin, inhibition of glial activation, anti-oxidant and anti-inflammatory activities could serve as important mechanisms underlying the neuroprotective effects of the used drugs in the rotenone model of PD. PMID- 27365174 TI - alpha2A adrenergic receptors highly expressed in mesoprefrontal dopamine neurons. AB - alpha2 adrenoreceptors (alpha2-ARs) play a key role in the control of noradrenaline and dopamine release in the medial prefrontal cortex (mPFC). Here, using UV-laser microdissection-based quantitative mRNA expression in individual neurons we show that in hTH-GFP rats, a transgenic line exhibiting intense and specific fluorescence in dopaminergic (DA) neurons, alpha2A adrenoreceptor (alpha2A-AR) mRNA is expressed at high and low levels in DA cells in the ventral tegmental area (VTA) and substantia nigra compacta (SNc), respectively. Confocal microscopy fluorescence immunohistochemistry revealed that alpha2A-AR immunoreactivity colocalized with tyrosine hydroxylase (TH) in nearly all DA cells in the VTA and SNc, both in hTH-GFP rats and their wild-type Sprague-Dawley (SD) counterparts. alpha2A-AR immunoreactivity was also found in DA axonal projections to the mPFC and dorsal caudate in the hTH-GFP and in the anterogradely labeled DA axonal projections from VTA to mPFC in SD rats. Importantly, the alpha2A-AR immunoreactivity localized in the DA cells of VTA and in their fibers in the mPFC was much higher than that in DA cells of SNc and their fibers in dorsal caudate, respectively. The finding that alpha2A-ARs are highly expressed in the cell bodies and axons of mesoprefrontal dopaminergic neurons provides a morphological basis to the vast functional evidence that somatodendritic and nerve-terminal alpha2A-AR receptors control dopaminergic activity and dopamine release in the prefrontal cortex. This finding raises the question whether alpha2A-ARs might function as autoreceptors in the mesoprefrontal dopaminergic neurons, replacing the lack of D2 autoreceptors. PMID- 27365175 TI - Nicotine-induced acute hyperactivity is mediated by dopaminergic system in a sexually dimorphic manner. AB - Short-term exposure to nicotine induces positive effects in mice, monkeys and humans, including mild euphoria, hyperactivity, and enhanced cognition. However, the underlying neural basis and molecular mechanisms for these effects remain poorly understood. Here, using a video recording system, we find that acute nicotine administration induces locomotor hyperactivity in Drosophila, similar to observations made in higher model organisms. Suppressing dopaminergic neurons or down-regulating dopamine 1-like receptor (DopR) abolishes this acute nicotine response, but surprisingly, does so only in male flies. Using a GFP reconstitution across synaptic partners (GRASP) approach, we show that dopaminergic neurons possess potential synaptic connections with acetylcholinergic neurons in wide regions of the brain. Furthermore, dopaminergic neurons are widely activated upon nicotine perfusion in both sexes, while the response curve differs significantly between the sexes. Moreover, knockdown of the beta1 nicotine acetylcholine receptor (nAChR) in dopaminergic neurons abolishes the acute nicotine response only in male flies, while panneural knock down occurs in both sexes. Taken together, our results reveal that in fruit flies, dopaminergic neurons mediate nicotine-induced acute locomotor hyperactivity in a sexually dimorphic manner, and Drosophila beta1 nAChR subunit plays a crucial role in this nicotine response. These findings provide important insights into the molecular and neural basis of acute nicotine effects, and the underlying mechanisms may play conserved roles across species. PMID- 27365176 TI - Paternal age and diet: The contributions of a father's experience to susceptibility for post-concussion symptomology. AB - In an attempt to improve current understanding of risk factors that influence individual susceptibility to poor outcomes following mild traumatic brain injury (mTBI) or concussion, this project investigated whether modifications to paternal experiences (Advanced Age (AA) or High-Fat Diet (HFD)) affected offspring susceptibility to behavioral symptomology and changes in gene expression following pediatric concussion in a rodent model. The study demonstrated that paternal treatment prior to conception altered behavioral outcomes and molecular characterization of offspring. Offspring of AA fathers demonstrated abnormal behavioral performance when compared to offspring of control fathers. Similarly, paternal HFD altered pathophysiological outcomes for offspring, contributing to the heterogeneity in post-concussion syndrome. Additionally, this study provided insight into the mechanisms that mediate non-genetic paternal inheritance. Paternal treatment and the mTBI significantly influenced expression of a majority of the genes under examination in the prefrontal cortex, hippocampus, and nucleus accumbens, with changes being dependent upon sex and the brain region examined. These epigenetic changes may have contributed to the differences in offspring susceptibility to concussion. PMID- 27365177 TI - The Development of a Nystagmus-Specific Quality-of-Life Questionnaire. AB - PURPOSE: To develop a nystagmus-specific quality-of-life (QOL) questionnaire derived from patient concerns based on eudaimonic aspects of well-being. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 206 participants with nystagmus for factor analysis phase and an additional 42 participants with nystagmus for construct validity phase. METHODS: Questionnaire items were written on the basis of the 6 domains of everyday living affected by nystagmus that were elicited by previous semistructured interviews conducted with 21 people with nystagmus. After consultation with 8 nystagmus experts, 37 items were administered to 206 people with nystagmus. Factor analysis was used to identify latent factors among the items and identify items to propose new nystagmus QOL scales. Cronbach's alpha was used to assess the internal reliability of the new scales. To assess for discriminate and concurrent validity between the new nystagmus scales and an existing vision-related QOL tool, the Visual Function Questionnaire-25 (VFQ-25) was administered to 42 additional participants. MAIN OUTCOME MEASURES: Questionnaire response scores on nystagmus-specific QOL items. RESULTS: The factor analysis revealed the retention of 29 items to form a measure comprising 2 distinct subscales reflecting "personal and social" and "physical and environmental" functioning as relating to nystagmus-specific QOL. The Cronbach's alpha coefficients for the "personal and social" functioning scale and "physical and environmental" functioning were 0.95 and 0.93, respectively. Tests for validity of the measure, consistent with a priori predictions, when compared with the VFQ-25, revealed the "physical and environmental" subscale showed concurrent validity (0.88), whereas the "personal and social" subscale was demonstrated to have discriminative validity (0.81). CONCLUSIONS: We have developed a 29-item, nystagmus-specific QOL questionnaire (NYS-29) based on eudaimonic aspects of well being with subscales that address not only physical functioning but also psycho social issues. The NYS-29 is grounded in the perspectives and concerns of those who have nystagmus and can be used to determine the impact of nystagmus on daily living in terms of both physical and psychosocial aspects. PMID- 27365179 TI - You get what you give: children's karmic bargaining. AB - Do children believe in karma - the notion that life events occur to punish or reward our moral behavior? In three experiments, we investigate 4-6-year-old children's willingness to endorse and engage in the practice of performing good acts in order to secure an unrelated future desired outcome, so-called 'karmic bargaining'. Most children agreed that performing a morally good social behavior, but not a morally negative or morally neutral non-social behavior, would increase the chances that future desired outcomes would occur, in both first-party and third-party contexts. About half of children also engaged in karmic bargaining behavior themselves. We conclude that a belief in karma may therefore reflect a broad, early-emerging teleological bias to interpret life events in terms of agency, purpose, and design. PMID- 27365178 TI - Stress and Protists: No life without stress. AB - We report a summary of the symposium "Stress and Protists: No life without stress", which was held in September 2015 on the VII European Congress of Protistology in partnership with the International Society of Protistologists (Seville, Spain). We present an overview on general comments and concepts on cellular stress which can be also applied to any protist. Generally, various environmental stressors may induce similar cell responses in very different protists. Two main topics are reported in this manuscript: (i) metallic nanoparticles as environmental pollutants and stressors for aquatic protists, and (ii) ultraviolet radiation - induced stress and photoprotective strategies in ciliates. Model protists such as Chlamydomonas reinhardtii and Tetrahymena thermophila were used to assess stress caused by nanoparticles while stress caused by ultraviolet radiation was tested with free living planktonic ciliates as well as with the symbiont-bearing model ciliate Paramecium bursaria. For future studies, we suggest more intensive analyses on protist stress responses to specific environmental abiotic and/or biotic stressors at molecular and genetic levels up to ecological consequences and food web dynamics. PMID- 27365180 TI - Hereditary haemochromatosis. PMID- 27365183 TI - Correlation between the modified Huddart and Bodenham index and the GOSLON yardstick for assessing occlusal characteristics at 5 and 10 years of age in individuals born with unilateral cleft lip and palate. AB - BACKGROUND: The Great Ormond Street, London and Oslo, Norway (GOSLON) yardstick and the modified Huddart and Bodenham (MHB) index are two indices for evaluating study models to discern the effects of treatment in individuals born with unilateral cleft lip and palate (UCLP). GOSLON is a tool for ranking study models based on their sagittal, vertical, and transversal planes that requires calibration of the examiners. MHB is a tool for scoring the arch constriction between the jaws for each tooth pair, with scores ranging from +1 to -3. AIM: Our study aimed to identify the degree of correlation between the GOSLON and MHB indices and to compare inter- and intra-examiner reliability. MATERIAL: The study scored 107 study models of 76 children aged 5 (n = 50) and 10 (n = 57) years using the MHB and GOSLON indices. RESULTS: We found a very high intra- and inter examiner reliability (>0.90) for the MHB and the GOSLON indices as well as a moderate to high negative correlation between the two. Among 5-year-olds, the relationship between the MHB and the GOSLON was linear, while among 10-year-olds, GOSLON Groups 2 and 4 occurred most frequently, with a corresponding wide range in MHB. CONCLUSION: Standardization of maxillary arch constriction measurements following CLP treatment would help evaluation of treatment outcome and make comparability between studies possible. We found a moderate to high correlation between GOSLON and MHB. Both indices showed very good intra- and inter-examiner reliability. MHB is a more sensitive system compared to GOSLON, with a greater range of scoring (40 grades) than GOSLON (five categories). PMID- 27365181 TI - Breath-taking jobs: a case-control study of respiratory work disability by occupation in Norway. AB - BACKGROUND: The current knowledge on respiratory work disability is based on studies that used crude categories of exposure. This may lead to a loss of power, and does not provide sufficient information to allow targeted workplace interventions and follow-up of patients with respiratory symptoms. OBJECTIVES: The aim of this study was to identify occupations and specific exposures associated with respiratory work disability. METHODS: In 2013, a self administered questionnaire was mailed to a random sample of the general population, aged 16-50, in Telemark County, Norway. We defined respiratory work disability as a positive response to the survey question: 'Have you ever had to change or leave your job because it affected your breathing?' Occupational exposures were assessed using an asthma-specific job-exposure matrix, and comparison of risks was made for cases and a median of 50 controls per case. RESULTS: 247 workers had changed their work because of respiratory symptoms, accounting for 1.7% of the respondents ever employed. The 'breath-taking jobs' were cooks/chefs: adjusted OR 3.6 (95% CI 1.6 to 8.0); welders: 5.2 (2.0 to 14); gardeners: 4.5 (1.3 to 15); sheet metal workers: 5.4 (2.0 to 14); cleaners: 5.0 (2.2 to 11); hairdressers: 6.4 (2.5 to 17); and agricultural labourers: 7.4 (2.5 to 22). Job changes were also associated with a variety of occupational exposures, with some differences between men and women. CONCLUSIONS: Self-report and job-exposure matrix data showed similar findings. For the occupations and exposures associated with job change, preventive measures should be implemented. PMID- 27365182 TI - Determination of the mesio-distal tooth width via 3D imaging techniques with and without ionizing radiation: CBCT, MSCT, and uCT versus MRI. AB - Objective: The purpose of this study was to estimate the feasibility and accuracy of mesio-distal width measurements with magnetic resonance imaging (MRI) in comparison to conventional 3D imaging techniques [multi-slice CT (MSCT), cone beam CT (CBCT), and uCT]. The measured values of the tooth widths were compared to each other to estimate the amount of radiation necessary to enable orthodontic diagnostics. Material and Methods: Two pig skulls were measured with MSCT, CBCT, uCT, and MRI. Three different judges were asked to determine the mesio-distal tooth width of 14 teeth in 2D tomographic images and in 3D segmented images via a virtual ruler in every imaging dataset. Results: Approximately 19% (27/140) of all test points in 2D tomographic slice images and 12% (17/140) of the test points in 3D segmented images showed a significant difference (P <= 0.05). The largest significant difference was 1.6mm (P < 0.001). There were fewer significant differences in the measurement of the tooth germs than in erupted teeth. Conclusions: Measurement of tooth width by MRI seems to be clinically equivalent to the conventional techniques (CBCT and MSCT). Tooth germs are better illustrated than erupted teeth on MRI. Three-dimensional segmented images offer only a slight advantage over 2D tomographic slice images. MRI, which avoids radiation, is particularly appealing in adolescents if these data can be corroborated in further studies. PMID- 27365185 TI - Comment on: Pristinamycin in the treatment of MSSA bone and joint infection. PMID- 27365184 TI - Association between statins and infections among patients with diabetes: a cohort and prescription sequence symmetry analysis. AB - PURPOSE: A previous meta-analysis of randomized trials did not confirm findings from observational studies that suggested that statins reduce the risk of infection. However, animal experiments indicate that statins may be more effective in reducing the risk and/or the severity of infection among patients with diabetes. Hence, we evaluated the effect of statins on antibiotic prescriptions (a proxy for infections) among patients with drug-treated type 2 diabetes using two confounding-reducing observational designs. METHODS: We conducted a prescription sequence symmetry analysis and a cohort study using the IADB.nl pharmacy prescription database. For the prescription sequence symmetry analysis, a sequence ratio was calculated. The matched cohort study, comparing the time to first antibiotic prescription between periods that statins are initiated and non-use periods, was analyzed using stratified Cox regression. RESULTS: Prescription sequence symmetry analysis of 4684 patients with drug treated type 2 diabetes resulted in an adjusted sequence ratio of 0.86 (95% confidence interval [CI]: 0.81 to 0.91). Corresponding figures for the cohort analysis comparing 9852 statin-initiation with 4928 non-use periods showed similar results (adjusted hazard ratio: 0.88, 95%CI: 0.83 to 0.95). CONCLUSIONS: These findings suggest that statins are associated with a reduced risk of infections among patients with drug-treated type 2 diabetes. (c) 2016 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd. PMID- 27365186 TI - Benchmarking of methods for identification of antimicrobial resistance genes in bacterial whole genome data. AB - OBJECTIVES: Next generation sequencing (NGS) may be an alternative to phenotypic susceptibility testing for surveillance and clinical diagnosis. However, current bioinformatics methods may be associated with false positives and negatives. In this study, a novel mapping method was developed and benchmarked to two different methods in current use for identification of antibiotic resistance genes in bacterial WGS data. METHODS: A novel method, KmerResistance, which examines the co-occurrence of k-mers between the WGS data and a database of resistance genes, was developed. The performance of this method was compared with two previously described methods; ResFinder and SRST2, which use an assembly/BLAST method and BWA, respectively, using two datasets with a total of 339 isolates, covering five species, originating from the Oxford University Hospitals NHS Trust and Danish pig farms. The predicted resistance was compared with the observed phenotypes for all isolates. To challenge further the sensitivity of the in silico methods, the datasets were also down-sampled to 1% of the reads and reanalysed. RESULTS: The best results were obtained by identification of resistance genes by mapping directly against the raw reads. This indicates that information might be lost during assembly. KmerResistance performed significantly better than the other methods, when data were contaminated or only contained few sequence reads. CONCLUSIONS: Read mapping is superior to assembly-based methods and the new KmerResistance seemingly outperforms currently available methods particularly when including datasets with few reads. PMID- 27365187 TI - Activation of type II NADH dehydrogenase by quinolinequinones mediates antitubercular cell death. AB - OBJECTIVES: Quinolinequinones (QQ) have been shown to inhibit the growth of mycobacterial species, but their mode(s) of action and molecular target(s) remain unknown. To facilitate further development of QQ as antimycobacterial drugs, we investigated the molecular mechanism and target of QQ in mycobacteria. METHODS: Cell viability of Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guerin was determined in the presence of QQ8c, a representative QQ compound, and isoniazid, a frontline antitubercular drug. The effect of QQ8c on mycobacterial energetics was studied using inverted membrane vesicles. NADH oxidation and formation of reactive oxygen species (ROS) were measured in the presence and absence of KCN. Generation of ROS was measured via oxygen consumption in an oxygen electrode. The effects of QQ8c were compared with the antimycobacterial drug clofazimine in side-by-side experiments. RESULTS: QQ8c challenge resulted in complete sterilization of cultures with no refractory resistant population observed. QQ8c stimulated NADH oxidation by type II NADH dehydrogenase (NDH-2) and oxygen consumption in inverted membrane vesicles. Large quantities of ROS were produced in the presence of QQ8. Even when oxygen consumption was blocked with KCN, activation of NDH-2 by QQ8c occurred suggesting QQ8c was redox cycling. CONCLUSIONS: QQ8c targets NDH-2 of the mycobacterial respiratory chain leading to activation of NADH oxidation and generating bactericidal levels of ROS in a manner similar to, but more effectively than, the antimycobacterial drug clofazimine. Our results validate respiratory-generated ROS as an avenue for antimycobacterial drug development. PMID- 27365188 TI - True incidence of tigecycline-induced pancreatitis: how many cases are we missing? PMID- 27365189 TI - Optimising cervical cancer screening programs: how to evaluate incremental changes? PMID- 27365190 TI - The modulating role of group stability on fitness effects of group size is different in females and males of a communally rearing rodent. AB - Group size may influence fitness benefits and costs that emerge from cooperative and competitive interactions in social species. However, evidence from plural breeding mammals indicates that group size is insufficient to explain variation in direct fitness, implying other attributes of social groups were overlooked. We studied the natural population of a social rodent during 5 years to test the hypothesis that social stability - in terms of group composition - modulates the effects of increasing number of breeding females (a proxy of communal rearing) and males on the number of offspring weaned (sired) and on the number of offspring weaned (sired) surviving to breeding age (two proxies of direct fitness). We quantified the effects of social stability (measured as changes in female or male group members between mating and the onset of lactation) on these fitness measures. We used live trapping, telemetry and DNA markers to determine social and fitness measures. Social stability in degus was variable in terms of the number of changes in group composition across groups. Low stability was mostly due to mortality and emigration of group members. Results supported a modulating role of social stability on the relationship between group size and the number of offspring weaned (sired). Stability in female and male group composition were both modulators of fitness to females and males. The modulatory role of stability was sex specific, where high social stability was often fitness beneficial to the females. Instead, low social stability was fitness enhancing to the males. PMID- 27365191 TI - Microsporidia-Emergent Pathogens in the Global Food Chain (Trends in Parasitology 32, 336-348; April 2, 2016). PMID- 27365194 TI - Assessment of Risk Factors Associated with Nipple Reconstruction. PMID- 27365192 TI - Sequence-Defined Oligomers from Hydroxyproline Building Blocks for Parallel Synthesis Applications. AB - The functionality of natural biopolymers has inspired significant effort to develop sequence-defined synthetic polymers for applications including molecular recognition, self-assembly, and catalysis. Conjugation of synthetic materials to biomacromolecules has played an increasingly important role in drug delivery and biomaterials. We developed a controlled synthesis of novel oligomers from hydroxyproline-based building blocks and conjugated these materials to siRNA. Hydroxyproline-based monomers enable the incorporation of broad structural diversity into defined polymer chains. Using a perfluorocarbon purification handle, we were able to purify diverse oligomers through a single solid-phase extraction method. The efficiency of synthesis was demonstrated by building 14 unique trimers and 4 hexamers from 6 diverse building blocks. We then adapted this method to the parallel synthesis of hundreds of materials in 96-well plates. This strategy provides a platform for the screening of libraries of modified biomolecules. PMID- 27365195 TI - Intramammary Aneurysm Presenting as a Breast Mass. PMID- 27365196 TI - Breast Cancer with Metastasis to the Nasopharynx and Paranasal Sinuses. PMID- 27365197 TI - Better predictive value of axillary lymph node (ALN) status after systemic therapy for operable HER2-overexpressing breast cancer: A single-institution retrospective study. AB - BACKGROUND: Thresholds for using Preoperative Systemic Therapy (PreST) have decreased to include early breast cancer. This study investigates the predictive value of axillary lymph node (ALN) status before and after systemic therapy and discusses whether it is better to receive PreST first in operable HER2 overexpressing breast cancer patients. METHODS: From January 2008 to June 2013 at Fudan University Shanghai Cancer Center, we identified 406 eligible female patients with stage II-IIIa, operable and pathologically confirmed HER2 overexpressing invasive ductal carcinoma. Of these patients, 269 underwent surgery first followed by chemotherapy plus trastuzumab (chemo-trastuzumab) (SurgFirst group), whereas 137 received systemic chemo-trastuzumab therapy first followed by surgery (STFirst group). Disease-free survival (DFS) and overall survival (OS) were evaluated according to different ALN statuses using the Kaplan Meier method. Multivariate COX model analyses were also conducted. RESULTS: The median follow-up time was 47 months (IQR: 37-60). Both ALN status and overall pathological complete remission (pCR) status were shown to be significant for the prediction of DFS (p = 0.001 and p = 0.005, respectively) and OS (p = 0.009 and p = 0.027, respectively) in the STFirst group. However, patients with positive ALN(s) did not experience significantly poorer survival compared with those with negative ALN in the SurgFirst group. The adjusted hazard ratios (HRs) for positive ALN status in the STFirst and SurgFirst groups were 6.66 (p = 0.001, 95%CI: 2.18-20.38) and 2.40 (p = 0.126, 95%CI: 0.78-7.34), respectively. CONCLUSION: The ALN status after systemic chemo-trastuzumab therapy better predicts the survival outcome. We recommend the application of PreST followed by surgery in patients with operable HER2-overexpressing breast cancer. PMID- 27365193 TI - Colonization and effector functions of innate lymphoid cells in mucosal tissues. AB - Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. PMID- 27365198 TI - Improved survival associated with a balanced structure between adenomatous and squamous components in patients with adenosquamous carcinoma of the lung. AB - BACKGROUND: Primary adenosquamous carcinoma (ASC) of the lung is rare and its biological behavior has not yet been thoroughly described. The aim of this study was to analyze the clinicopathological characteristics and prognostic factors associated with ASC. MATERIALS: Clinical records of patients with ASC of the lung who underwent surgery between October 2008 and December 2014 in a single institution were retrospectively reviewed. RESULTS: A total of 205 patients were identified. Patients with balanced structural components had significantly better prognosis than those with squamous (p = 0.014) or adenomatous (p < 0.001) predominance, and those with N0, N1, and N2 ASC (N0 vs. N1 [ p = 0.031] and N1 vs. N2 [p = 0.037], respectively), or stage I, II and IIIA ASC (stage I vs. II [p = 0.021] and stage II vs. IIIA [p = 0.007], respectively) had significant differences with respect to overall survival (OS). Multivariate analysis identified structural components (p = 0.011), tumor, node and metastasis (TNM) status (p < 0.001), and adjuvant chemotherapy (p = 0.008) as significantly prognostic factors for OS, and structural components (p = 0.030), TNM stage (p < 0.001) and adjuvant chemotherapy (p = 0.005) as the corresponding variables for disease-free survival. CONCLUSIONS: A balanced structure between adenomatous and squamous components in patients with primary ASC of the lung was associated with better prognosis. PMID- 27365199 TI - The utility of the MELD score in predicting mortality following liver resection for metastasis. AB - BACKGROUND: The MELD score has been demonstrated to be predictive of hepatectomy outcomes in mixed patient samples of primary and secondary liver cancers. Because MELD is a measure of hepatic dysfunction, prior conclusions may rely on the high prevalence of cirrhosis observed with primary lesions. This study aims to evaluate MELD score as a predictor of mortality and develop a risk prediction model for patients specifically undergoing hepatic metastasectomy. METHODS: ACS NSQIP 2005-2013 was analyzed to select patients who had undergone liver resections for metastases. A receiver operating characteristic (ROC) analysis determined the MELD score most associated with 30-day mortality. A literature review identified variables that impact hepatectomy outcomes. Significant factors were included in a multivariable analysis (MVA). A risk calculator was derived from the final multivariable model. RESULTS: Among the 14,919 patients assessed, the mortality rate was 2.7%, and the median MELD was 7.3 (range = 34.4). A MELD of 7.24 was identified by ROC (sensitivity = 81%, specificity = 51%, c-statistic = 0.71). Of all patients above this threshold, 4.4% died at 30 days vs. 1.1% in the group <=7.24. This faction represented 50.1% of the population but accounted for 80.3% of all deaths (p < 0.001). The MVA revealed mortality to be increased 2.6-times (OR = 2.55, 95%CI 1.69-3.84, p < 0.001). A risk calculator was successfully developed and validated. CONCLUSIONS: MELD>7.24 is an important predictor of death following hepatectomy for metastasis and may prompt a detailed assessment with the provided risk calculator. Attention to MELD in the preoperative setting will improve treatment planning and patient education prior to oncologic liver resection. PMID- 27365200 TI - The prevention issue. PMID- 27365201 TI - We neglect primary HIV prevention at our peril. PMID- 27365202 TI - The HIV prevention cascade: more smoke than thunder? PMID- 27365203 TI - Maximising HIV prevention by balancing the opportunities of today with the promises of tomorrow: a modelling study. AB - BACKGROUND: Many ways of preventing HIV infection have been proposed and more are being developed. We sought to construct a strategic approach to HIV prevention that would use limited resources to achieve the greatest possible prevention impact through the use of interventions available today and in the coming years. METHODS: We developed a deterministic compartmental model of heterosexual HIV transmission in South Africa and formed assumptions about the costs and effects of a range of interventions, encompassing the further scale-up of existing interventions (promoting condom use, male circumcision, early antiretroviral therapy [ART] initiation for all [including increased HIV testing and counselling activities], and oral pre-exposure prophylaxis [PrEP]), the introduction of new interventions in the medium term (offering intravaginal rings, long-acting injectable antiretroviral drugs) and long term (vaccine, broadly neutralising antibodies [bNAbs]). We examined how available resources could be allocated across these interventions to achieve maximum impact, and assessed how this would be affected by the failure of the interventions to be developed or scaled up. FINDINGS: If all interventions are available, the optimum mix would place great emphasis on the following: scale-up of male circumcision and early ART initiation with outreach testing, as these are available immediately and assumed to be low cost and highly efficacious; intravaginal rings targeted to sex workers; and vaccines, as these can achieve a large effect if scaled up even if imperfectly efficacious. The optimum mix would rely less on longer term developments, such as long-acting antiretroviral drugs and bNAbs, unless the costs of these reduced. However, if impossible to scale up existing interventions to the extent assumed, emphasis on oral PrEP, intravaginal rings, and long-acting antiretroviral drugs would increase. The long-term effect on the epidemic is most affected by scale-up of existing interventions and the successful development of a vaccine. INTERPRETATION: With current information, a strategic approach in which limited resources are used to maximise prevention impact would focus on strengthening the scale-up of existing interventions, while pursuing a workable vaccine and developing other approaches that can be used if further scale-up of existing interventions is limited. FUNDING: Bill & Melinda Gates Foundation. PMID- 27365204 TI - Providing a conceptual framework for HIV prevention cascades and assessing feasibility of empirical measurement with data from east Zimbabwe: a case study. AB - BACKGROUND: The HIV treatment cascade illustrates the steps required for successful treatment and is a powerful advocacy and monitoring tool. Similar cascades for people susceptible to infection could improve HIV prevention programming. We aim to show the feasibility of using cascade models to monitor prevention programmes. METHODS: Conceptual prevention cascades are described taking intervention-centric and client-centric perspectives to look at supply, demand, and efficacy of interventions. Data from two rounds of a population-based study in east Zimbabwe are used to derive the values of steps for cascades for voluntary medical male circumcision (VMMC) and for partner reduction or condom use driven by HIV testing and counselling (HTC). FINDINGS: In 2009 to 2011 the availability of circumcision services was negligible, but by 2012 to 2013 about a third of the population had access. However, where it was available only 12% of eligible men sought to be circumcised leading to an increase in circumcision prevalence from 3.1% to 6.9%. Of uninfected men, 85.3% did not perceive themselves to be at risk of acquiring HIV. The proportions of men and women tested for HIV increased from 27.5% to 56.6% and from 61.1% to 79.6%, respectively, with 30.4% of men tested self-reporting reduced sexual partner numbers and 12.8% reporting increased condom use. INTERPRETATION: Prevention cascades can be populated to inform HIV prevention programmes. In eastern Zimbabwe programmes need to provide greater access to circumcision services and the design and implementation of associated demand creation activities. Whereas, HTC services need to consider how to increase reductions in partner numbers or increased condom use or should not be considered as contributing to prevention services for the HIV-negative adults. FUNDING: Wellcome Trust and Bill & Melinda Gates Foundation. PMID- 27365205 TI - Interventions to strengthen the HIV prevention cascade: a systematic review of reviews. AB - BACKGROUND: Much progress has been made in interventions to prevent HIV infection. However, development of evidence-informed prevention programmes that translate the efficacy of these strategies into population effect remain a challenge. In this systematic review, we map current evidence for HIV prevention against a new classification system, the HIV prevention cascade. METHODS: We searched for systematic reviews on the effectiveness of HIV prevention interventions published in English from Jan 1, 1995, to July, 2015. From eligible reviews, we identified primary studies that assessed at least one of: HIV incidence, HIV prevalence, condom use, and uptake of HIV testing. We categorised interventions as those seeking to increase demand for HIV prevention, improve supply of HIV prevention methods, support adherence to prevention behaviours, or directly prevent HIV. For each specific intervention, we assigned a rating based on the number of randomised trials and the strength of evidence. FINDINGS: From 88 eligible reviews, we identified 1964 primary studies, of which 292 were eligible for inclusion. Primary studies of direct prevention mechanisms showed strong evidence for the efficacy of pre-exposure prophylaxis (PrEP) and voluntary medical male circumcision. Evidence suggests that interventions to increase supply of prevention methods such as condoms or clean needles can be effective. Evidence arising from demand-side interventions and interventions to promote use of or adherence to prevention tools was less clear, with some strategies likely to be effective and others showing no effect. The quality of the evidence varied across categories. INTERPRETATION: There is growing evidence to support a number of efficacious HIV prevention behaviours, products, and procedures. Translating this evidence into population impact will require interventions that strengthen demand for HIV prevention, supply of HIV prevention technologies, and use of and adherence to HIV prevention methods. FUNDING: Bill & Melinda Gates Foundation. PMID- 27365206 TI - The HIV prevention cascade: integrating theories of epidemiological, behavioural, and social science into programme design and monitoring. AB - Theories of epidemiology, health behaviour, and social science have changed the understanding of HIV prevention in the past three decades. The HIV prevention cascade is emerging as a new approach to guide the design and monitoring of HIV prevention programmes in a way that integrates these multiple perspectives. This approach recognises that translating the efficacy of direct mechanisms that mediate HIV prevention (including prevention products, procedures, and risk reduction behaviours) into population-level effects requires interventions that increase coverage. An HIV prevention cascade approach suggests that high coverage can be achieved by targeting three key components: demand-side interventions that improve risk perception and awareness and acceptability of prevention approaches; supply-side interventions that make prevention products and procedures more accessible and available; and adherence interventions that support ongoing adoption of prevention behaviours, including those that do and do not involve prevention products. Programmes need to develop delivery platforms that ensure these interventions reach target populations, to shape the policy environment so that it facilitates implementation at scale with high quality and intensity, and to monitor the programme with indicators along the cascade. PMID- 27365207 TI - HIV Prevention 2020: a framework for delivery and a call for action. AB - Although effective programmes are available and several countries have seen substantial declines in new HIV infections, progress in the reduction of adult HIV incidence has been slower than expected worldwide and many countries have not had large decreases in new infections in adults despite large reductions in paediatric infections. Reasons for slow progress include inadequate commitment, investment, focus, scale, and quality of implementation of prevention and treatment interventions. The UNAIDS-Lancet Commission on Defeating AIDS-Advancing Global Health reported that the provision of large-scale, effective HIV prevention programmes has failed and called on stakeholders to "get serious about HIV prevention". An ambitious worldwide target has been set by UNAIDS to reduce new infections below 500 000 by 2020-a 75% reduction from 2010. Models show that such a reduction requires a combination of primary prevention interventions and preventative effects of treatment. Achievement of the target will require more effective delivery of HIV prevention for sufficient coverage in populations at greatest risk of infection ensuring that interventions that have proved effective are made available, barriers to their uptake are overcome, demand is created, and use is consistent and occurs at the right scale with high coverage. This paper discusses how programmatic targets for prevention in a worldwide plan could be used to re-energise the HIV prevention approach. A management framework is proposed outlining global, regional, national, and subnational actions and is summarised in a call for action on HIV prevention for 2020. PMID- 27365208 TI - Regulated expression of the prostacyclin receptor (IP) gene by androgens within the vasculature: Combined role for androgens and serum cholesterol. AB - The prostanoid prostacyclin plays a key cardioprotective role within the vasculature. There is increasing evidence that androgens may also confer cardioprotection but through unknown mechanisms. This study investigated whether the androgen dihydrotestosterone (DHT) may regulate expression of the prostacyclin/I prostanoid receptor or, in short, the IP in platelet-progenitor megakaryoblastic and vascular endothelial cells. DHT significantly increased IP mRNA and protein expression, IP-induced cAMP generation and promoter (PrmIP) directed gene expression in all cell types examined. The androgen-responsive region was localised to a cis-acting androgen response element (ARE), which lies in close proximity to a functional sterol response element (SRE) within the core promoter. In normal serum conditions, DHT increased IP expression through classic androgen receptor (AR) binding to the functional ARE within the PrmIP. However, under conditions of low-cholesterol, DHT led to further increases in IP expression through an indirect mechanism involving AR-dependent upregulation of SCAP expression and enhanced SREBP1 processing & binding to the SRE within the PrmIP. Chromatin immunoprecipitation assays confirmed DHT-induced AR binding to the ARE in vivo in cells cultured in normal serum while, in conditions of low cholesterol, DHT led to increased AR and SREBP1 binding to the functional ARE and SRE cis-acting elements, respectively, within the core PrmIP resulting in further increases in IP expression. Collectively, these data establish that the human IP gene is under the transcriptional regulation of DHT, where this regulation is further influenced by serum-cholesterol levels. This may explain, in part, some of the protective actions of androgens within the vasculature. PMID- 27365209 TI - The RNA-binding profile of Acinus, a peripheral component of the exon junction complex, reveals its role in splicing regulation. AB - Acinus (apoptotic chromatin condensation inducer in the nucleus) is an RNA binding protein (RBP) originally identified for its role in apoptosis. It was later found to be an auxiliary component of the exon junction complex (EJC), which is deposited at exon junctions as a consequence of pre-mRNA splicing. To uncover the cellular functions of Acinus and investigate its role in splicing, we mapped its endogenous RNA targets using the cross-linking immunoprecipitation protocol (iCLIP). We observed that Acinus binds to pre-mRNAs, associating specifically to a subset of suboptimal introns, but also to spliced mRNAs. We also confirmed the presence of Acinus as a peripheral factor of the EJC. RNA-seq was used to investigate changes in gene expression and alternative splicing following siRNA-mediated depletion of Acinus in HeLa cells. This analysis revealed that Acinus is preferentially required for the inclusion of specific alternative cassette exons and also controls the faithful splicing of a subset of introns. Moreover, a large number of splicing changes can be related to Acinus binding, suggesting a direct role of Acinus in exon and intron definition. In particular, Acinus regulates the splicing of DFFA/ICAD transcript, a major regulator of DNA fragmentation. Globally, the genome-wide identification of RNA targets of Acinus revealed its role in splicing regulation as well as its involvement in other cellular pathways, including cell cycle progression. Altogether, this study uncovers new cellular functions of an RBP transiently associated with the EJC. PMID- 27365211 TI - Cognitive and Affective Representations of Active Surveillance as a Treatment Option for Low-Risk Prostate Cancer. AB - Benefits of early diagnosis and treatment remain debatable for men with low-risk prostate cancer. Active surveillance (AS) is an alternative to treatment. The goal of AS is to identify patients whose cancer is progressing rapidly while avoiding treatment in the majority of patients. The purpose of this study was to explore cognitive and affective representations of AS within a clinical environment that promotes AS a viable option for men with low-risk prostate cancer. Participants included patients for whom AS and active treatment were equally viable options, as well as practitioners who were involved in consultations for prostate cancer. Data were generated from semistructured interviews and audits of consultation notes and were analyzed using thematic analysis. Nineteen patients and 16 practitioners completed a semistructured interview. Patients generally viewed AS as a temporary strategy that was largely equated with inaction. There was variation in the degree to which inaction was viewed as warranted or favorable. Patient perceptions of AS were generally malleable and able to be influenced by information from trusted sources. Encouraging slow deliberation and multiple consultations may facilitate greater understanding and acceptance of AS as a viable treatment option for low-risk prostate cancer. PMID- 27365210 TI - The fission yeast MTREC and EJC orthologs ensure the maturation of meiotic transcripts during meiosis. AB - Meiosis is a highly regulated process by which genetic information is transmitted through sexual reproduction. It encompasses unique mechanisms that do not occur in vegetative cells, producing a distinct, well-regulated meiotic transcriptome. During vegetative growth, many meiotic genes are constitutively transcribed, but most of the resulting mRNAs are rapidly eliminated by the Mmi1-MTREC (Mtl1-Red1 core) complex. While Mmi1-MTREC targets premature meiotic RNAs for degradation by the nuclear 3'-5' exoribonuclease exosome during mitotic growth, its role in meiotic gene expression during meiosis is not known. Here, we report that Red5, an essential MTREC component, interacts with pFal1, an ortholog of eukaryotic translation initiation factor eIF4aIII in the fission yeast Schizosaccharomyces pombe In mammals, together with MAGO (Mnh1), Rnps1, and Y14, elF4AIII (pFal1) forms the core of the exon junction complex (EJC), which is essential for transcriptional surveillance and localization of mature mRNAs. In fission yeast, two EJC orthologs, pFal1 and Mnh1, are functionally connected with MTREC, specifically in the process of meiotic gene expression during meiosis. Although pFal1 interacts with Mnh1, Y14, and Rnps1, its association with Mnh1 is not disrupted upon loss of Y14 or Rnps1. Mutations of Red1, Red5, pFal1, or Mnh1 produce severe meiotic defects; the abundance of meiotic transcripts during meiosis decreases; and mRNA maturation processes such as splicing are impaired. Since studying meiosis in mammalian germline cells is difficult, our findings in fission yeast may help to define the general mechanisms involved in accurate meiotic gene expression in higher eukaryotes. PMID- 27365212 TI - Young Men, Help-Seeking, and Mental Health Services: Exploring Barriers and Solutions. AB - International research has identified young men as reluctant to seek help for mental health problems. This research explored barriers and solutions to professional help seeking for mental health problems among young men living in the North West of Ireland. A qualitative approach, using two focus groups with six participants each and five face-to-face interviews, was conducted with men aged 18 to 24 years (total N = 17). Data were analyzed using thematic analysis. Seven key themes of barriers to professional help seeking were identified: "acceptance from peers," "personal challenges," "cultural and environmental influences," "self-medicating with alcohol," "perspectives around seeking professional help," "fear of homophobic responses," and "traditional masculine ideals." Five key themes of solutions to these barriers included "tailored mental health advertising," "integrating mental health into formal education," "education through semiformal support services," "accessible mental health care," and "making new meaning." Interesting findings on barriers include fear of psychiatric medication, fear of homophobic responses from professionals, the legacy of Catholic attitudes, and the genuine need for care. This study offers an in-depth exploration of how young men experience barriers and uniquely offers solutions identified by participants themselves. Youth work settings were identified as a resource for engaging young men in mental health work. Young men can be encouraged to seek help if services and professionals actively address barriers, combining advertising, services, and education, with particular attention and respect to how and when young men seek help and with whom they want to share their problems. PMID- 27365213 TI - Severity of Alopecia Predicts Coronary Changes and Arterial Stiffness in Untreated Hypertensive Men. AB - An association between androgenic alopecia (AGA), coronary artery disease, and hypertension has been reported in previous epidemiological studies. The authors evaluated the relationship of target organ damage caused by hypertension with AGA in 101 newly diagnosed and untreated hypertension men with mild to moderate AGA (AGAm ), severe AGA (AGAs ), and non-AGA. Pulse wave velocity (PWV), office and 24-hour pulse pressure (PP), carotid intima-media thickness (IMT), left ventricular hypertrophy (LVH), coronary flow reserve (CFRd), and AGA severity by Hamilton-Norwood scale were estimated. CFRd was significantly impaired in AGAs patients compared with AGAm (P=.007) and non-AGA patients (P=.02). No differences were found within groups regarding PWV, PP, IMT, and LVH. AGA severity was related to CFRd (independently) and PP while AGA duration and age of onset were related to CFRd and PP, respectively. The authors conclude that impaired coronary microcirculation and aortic stiffness might precede the appearance of significant stenotic coronary lesions in hypertensive patients with severe AGA. In addition, hypertensive patients with severe and early AGA onset seem to be exposed to an augmented cardiovascular risk. PMID- 27365214 TI - Clinical Pharmacokinetics of Vemurafenib in BRAF-Mutated Melanoma Patients. PMID- 27365215 TI - Vaginal fibroepithelial polyp in a neonate: a rare case. PMID- 27365216 TI - Clusterin expression is upregulated following acute head injury and localizes to astrocytes in old head injury. AB - There is mounting evidence linking traumatic brain injury (TBI) to neurodegeneration. Clusterin (apolipoprotein J or ApoJ) is a complement inhibitor that appears to have a neuroprotective effect in response to tissue damage and has been reported to be upregulated in Alzheimer's disease. Here we investigated the time course and cellular expression pattern of clusterin in human TBI. Tissue from 32 patients with TBI of varying survival times (from under 30 min to 10 months) was examined using immunohistochemistry for clusterin alongside other markers of neurodegeneration and neuroinflammation. TBI cases were compared to ischemic brain damage, Alzheimer's disease and controls. Double immunofluorescence was carried out in order to examine cellular expression. Clusterin was initially expressed in an axonal location less than 30 min following TBI and increased in intensity and the frequency of deposits with increasing survival time up to 24 h, after which it appeared to reduce in intensity but was still evident several weeks after injury. Clusterin was first evident in astrocytes after 45 min, being increasingly seen up to 48 h but remaining intense in TBI cases with long survival times. Our results suggest clusterin plays a role in modulating the inflammatory response of acute and chronic TBI and that it is a useful marker for TBI, particularly in cases with short survival times. Its prominent accumulation in astrocytes, alongside a mounting inflammatory response and activation of microglial cells supports a potential role in the neurodegenerative changes that occur as a result of TBI. PMID- 27365217 TI - Increasing Children's Voluntary Physical Activity Outside of School Hours Through Targeting Social Cognitive Theory Variables. AB - INTRODUCTION: Volume of moderate-to-vigorous physical activity completed during the elementary school day is insufficient, and associated with health risks. Improvements in theory-based psychosocial factors might facilitate increased out of-school physical activity. METHODS: A behaviorally based after-school care protocol, Youth Fit 4 Life, was tested for its association with increased voluntary, out-of-school physical activity and improvements in its theory-based psychosocial predictors in 9- to 12-year-olds. RESULTS: Increases over 12 weeks in out-of-school physical activity, and improvements in self-regulation for physical activity, exercise self-efficacy, and mood, were significantly greater in the Youth Fit 4 Life group (n = 88) when contrasted with a typical care control group (n = 57). Changes in the 3 psychosocial variables significantly mediated the group-physical activity change relationship (R(2) = .31, P < .001). Change in self-regulation was a significant independent mediator, and had a reciprocal relationship with change in out-of-school physical activity. In the Youth Fit 4 Life group, occurrence of 300 min/wk of overall physical activity increased from 41% to 71%. CONCLUSIONS: Targeting theory-based psychosocial changes within a structured after-school care physical activity program was associated with increases in children's overall time being physically active. After replication, large scale application will be warranted. PMID- 27365219 TI - Spotlights on our sister journals: Chem. Eur. J. 28/2016. PMID- 27365218 TI - Distinctive gut microbial community structure in both the wild and farmed Swan goose (Anser cygnoides). AB - Swan goose (Anser cygnoides) is currently one of the most popular economic wildfowl for rare birds breeding industries in several provinces of China. However, the farmed Swan geese, reared in artificial environment and fed on both natural and artificial diets, display a reduced reproductive rate compared to wild species. Little is known about the gut microbiota of this species, which could play a role in nutrient and energy metabolism, immune homeostasis and reproduction. The present comparative study was designed to provide a first characterization of gut microbial communities related to both wild and farmed Swan geese by 16 S rRNA sequences using the Illumina HiSeq platform. The results showed that dominant microbial components in both groups consisted of Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria. The abundances of these four phyla were not statistically different between the groups. At the genus level, significantly decreased abundance of Clostridium and increased abundance of SMB53, Enterococcus and Paenibacillus were observed in farmed group compared to wild group. The marked differences of genus level group-specific microbes create a baseline for future Swan goose microbiology research and make a valuable contribution to forming relationships between gut microbiota and domestic bird reproduction. PMID- 27365220 TI - Comparison of biosensor platforms in the evaluation of high affinity antibody antigen binding kinetics. AB - The acquisition of reliable kinetic parameters for the characterization of biomolecular interactions is an important component of the drug discovery and development process. While several benchmark studies have explored the variability of kinetic rate constants obtained from multiple laboratories and biosensors, a direct comparison of these instruments' performance has not been undertaken, and systematic factors contributing to data variability from these systems have not been discussed. To address these questions, a panel of ten high affinity monoclonal antibodies was simultaneously evaluated for their binding kinetics against the same antigen on four biosensor platforms: GE Healthcare's Biacore T100, Bio-Rad's ProteOn XPR36, ForteBio's Octet RED384, and Wasatch Microfluidics's IBIS MX96. We compared the strengths and weaknesses of these systems and found that despite certain inherent systematic limitations in instrumentation, the rank orders of both the association and dissociation rate constants were highly correlated between these instruments. Our results also revealed a trade-off between data reliability and sample throughput. Biacore T100, followed by ProteOn XPR36, exhibited excellent data quality and consistency, whereas Octet RED384 and IBIS MX96 demonstrated high flexibility and throughput with compromises in data accuracy and reproducibility. Our results support the need for a "fit-for-purpose" approach in instrument selection for biosensor studies. PMID- 27365221 TI - Determination of half-maximal inhibitory concentration using biosensor-based protein interaction analysis. AB - Half-maximal inhibitory concentration (IC50) is the most widely used and informative measure of a drug's efficacy. It indicates how much drug is needed to inhibit a biological process by half, thus providing a measure of potency of an antagonist drug in pharmacological research. Most approaches to determine IC50 of a pharmacological compound are based on assays that utilize whole cell systems. While they generally provide outstanding potency information, results can depend on the experimental cell line used and may not differentiate a compound's ability to inhibit specific interactions. Here we show using the secreted Transforming Growth Factor-beta (TGF-beta) family ligand BMP-4 and its receptors as example that surface plasmon resonance can be used to accurately determine IC50 values of individual ligand-receptor pairings. The molecular resolution achievable wih this approach can help distinguish inhibitors that specifically target individual complexes, or that can inhibit multiple functional interactions at the same time. PMID- 27365222 TI - Evaluation of the route dependency of the pharmacokinetics and neuro pharmacokinetics of tramadol and its main metabolites in rats. AB - Tramadol hydrochloride is a centrally acting analgesic used for the treatment of moderate-to-severe pain. It has three main metabolites: O-desmethyltramadol (M1), N-desmethyltramadol (M2), and N,O-didesmethyltramadol (M5). Because of the frequent use of tramadol by patients and drug abusers, the ability to determine the parent drug and its metabolites in plasma and cerebrospinal fluid is of great importance. In the present study, a pharmacokinetic approach was applied using two groups of five male Wistar rats administered a 20mg/kg dose of tramadol via intravenous (i.v.) or intraperitoneal (i.p.) routes. Plasma and CSF samples were collected at 5-360min following tramadol administration. Our results demonstrate that the plasma values of Cmax (C0 in i.v. group) and area under the curve (AUC)0 t for tramadol were 23,314.40+/-6944.85 vs. 3187.39+/-760.25ng/mL (Cmax) and 871.15+/-165.98 vs. 414.04+/-149.25MUg.min/mL in the i.v. and i.p. groups, respectively (p<0.05). However, there were no significant differences between i.v. and i.p. plasma values for tramadol metabolites (p>0.05). Tramadol rapidly penetrated the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) (5.00+/-0.00 vs. 10.00+/-5.77min in i.v. and i.p. groups, respectively). Tramadol and its metabolites (M1 and M2) were present to a lesser extent in the cerebrospinal fluid (CSF) than in the plasma. M5 hardly penetrated the CSF, owing to its high polarity. There was no significant difference between the AUC0-t of tramadol in plasma (414.04+/-149.25MUg.min/mL) and CSF (221.81+/-83.02MUg.min/mL) in the i.p. group. In addition, the amounts of metabolites (M1 and M2) in the CSF showed no significant differences following both routes of administration. There were also no significant differences among the Kp,uu,CSF(0-360) (0.51+/-0.12 vs. 0.63+/-0.04) and Kp,uu,CSF(0-infinity) (0.61+/-0.10 vs. 0.62+/-0.02) for i.v. and i.p. pathways, respectively (p>0.05). Drug targeting efficiency (DTE) values of tramadol after i.p. injection were more than unity for all scheduled time points. Considering the main analgesic effect of M1, it is hypothesized that both routes of administration may produce the same amount of analgesia. PMID- 27365223 TI - Biologics and the lung: TSLP and other epithelial cell-derived cytokines in asthma. AB - Asthma is a chronic airway inflammatory disorder with characteristic symptoms of dyspnea, wheeze, chest tightness and cough, and physiological abnormalities of variable airway obstruction, airway hyperresponsiveness, and in some patients with chronic long standing disease reduced lung function. The physiological abnormalities are due to chronic airway inflammation and underlying structural changes to the airway wall. The interaction between the airway epithelium and the environment is crucial to the pathobiology of asthma. Several recent discoveries have highlighted a crucial role of airway epithelial derived cytokines such as interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP). These cytokines are collectively known as epithelial "alarmins", which act solely or in concert to activate and potentiate the innate and humoral arms of the immune system in the presence of actual or perceive damage. Understanding the role of alarmins and how they are activated and released may allow the development of novel new therapeutics to treat asthma. This review describes the interactions between inhaled air, the pulmonary microbiome, airway epithelial cell layer and the alarmins, IL-25, IL-33 and TSLP. There is already compelling evidence for a role of TSLP in the airway responses to environmental allergens in allergic asthmatics, as well as in maintaining airway eosinophilic inflammation in these subjects. Further work is required to develop human monoclonal antibodies (hMabs) directed against IL-25 and IL-33 or their receptors, to help understand their role in the initiation and/or persistence of asthma. PMID- 27365224 TI - Iodine-125 implantation plus transarterial chemoembolization for the treatment of hepatocellular carcinoma of 3-5cm: A propensity score matching study. AB - BACKGROUND: Both iodine-125 implantation and transarterial chemoembolization (TACE) are feasible options for hepatocellular carcinoma (HCC). The aim of the research is to investigate whether iodine-125 implantation combined with TACE could improve the overall survival of patients with HCC of 3-5cm. METHODS: 144 patients with HCC of 3-5cm who underwent iodine-125 implantation plus TACE and TACE alone were retrospectively enrolled in this study. To reduce the selection bias, 55 matched pairs of patients were generated by propensity score matching (PSM). Their overall survival was compared by the Kaplan-Meier method. Independent prognostic factors were identified by Cox proportional hazards regression model. RESULTS: patients receiving iodine-125 implantation plus TACE have significantly better overall survival than patients receiving TACE alone (P<0.001). After PSM, treatment of iodine-125 plus TACE still provide better survival (1-year, 89.1% vs. 65.5%; 3-year, 51.0% vs. 7.4%; P<0.001). In multivariate analysis, BCLC stage, vascular invasion and treatment modality independently predicted the prognosis. No severe adverse events occurred in both groups. CONCLUSION: for HCC patients of 3-5cm for whom surgical intervention is not an option, iodine-125 implantation combined with TACE might be an effective and viable alternative to provide better overall survival. PMID- 27365225 TI - [Paroxysmal supraventricular tachycardia (PSVT): Two presentations. Two approaches]. PMID- 27365226 TI - The feasibility of a randomised controlled trial of physiotherapy for adults with joint hypermobility syndrome. AB - BACKGROUND: Joint hypermobility syndrome (JHS) is a heritable disorder associated with laxity and pain in multiple joints. Physiotherapy is the mainstay of treatment, but there is little research investigating its clinical effectiveness. OBJECTIVES: To develop a comprehensive physiotherapy intervention for adults with JHS; to pilot the intervention; and to conduct a pilot randomised controlled trial (RCT) to determine the feasibility of conducting a future definitive RCT. DESIGN: Patients' and health professionals' perspectives on physiotherapy for JHS were explored in focus groups (stage 1). A working group of patient research partners, clinicians and researchers used this information to develop the physiotherapy intervention. This was piloted and refined on the basis of patients' and physiotherapists' feedback (stage 2). A parallel two-arm pilot RCT compared 'advice' with 'advice and physiotherapy' (stage 3). Random allocation was via an automated randomisation service, devised specifically for the study. Owing to the nature of the interventions, it was not possible to blind clinicians or patients to treatment allocation. SETTING: Stage 1 - focus groups were conducted in four UK locations. Stages 2 and 3 - piloting of the intervention and the pilot RCT were conducted in two UK secondary care NHS trusts. PARTICIPANTS: Stage 1 - patient focus group participants (n = 25, three men) were aged > 18 years, had a JHS diagnosis and had received physiotherapy within the preceding 12 months. The health professional focus group participants (n = 16, three men; 14 physiotherapists, two podiatrists) had experience of managing JHS. Stage 2 - patient participants (n = 8) were aged > 18 years, had a JHS diagnosis and no other musculoskeletal conditions causing pain. Stage 3 - patient participants for the pilot RCT (n = 29) were as for stage 2 but the lower age limit was 16 years. INTERVENTION: For the pilot RCT (stage 3) the advice intervention was a one-off session, supplemented by advice booklets. All participants could ask questions specific to their circumstances and receive tailored advice. Participants were randomly allocated to 'advice' (no further advice or physiotherapy) or 'advice and physiotherapy' (an additional six 30-minute sessions over 4 months). The physiotherapy intervention was supported by a patient handbook and was delivered on a one-to-one patient-therapist basis. It aimed to increase patients' physical activity through developing knowledge, understanding and skills to better manage their condition. MAIN OUTCOME MEASURES: Data from patient and health professional focus groups formed the main outcome from stage 1. Patient and physiotherapist interview data also formed a major component of stages 2 and 3. The primary outcome in stage 3 related to the feasibility of a future definitive RCT [number of referrals, recruitment and retention rates, and an estimate of the value of information (VOI) of a future RCT]. Secondary outcomes included clinical measures (physical function, pain, global status, self-reported joint count, quality of life, exercise self-efficacy and adverse events) and resource use (to estimate cost-effectiveness). Outcomes were recorded at baseline, 4 months and 7 months. RESULTS: Stage 1 - JHS is complex and unpredictable. Physiotherapists should take a long-term holistic approach rather than treating acutely painful joints in isolation. Stage 2 - a user-informed physiotherapy intervention was developed and evaluated positively. Stage 3 - recruitment to the pilot RCT was challenging, primarily because of a perceived lack of equipoise between advice and physiotherapy. The qualitative evaluation provided very clear guidance to inform a future RCT, including enhancement of the advice intervention. Some patients reported that the advice intervention was useful and the physiotherapy intervention was again evaluated very positively. The rate of return of questionnaires was low in the advice group but reasonable in the physiotherapy group. The physiotherapy intervention showed evidence of promise in terms of primary and secondary clinical outcomes. The advice arm experienced more adverse events. The VOI analysis indicated the potential for high value from a future RCT. Such a trial should form the basis of future research efforts. CONCLUSION: A future definitive RCT of physiotherapy for JHS seems feasible, although the advice intervention should be made more robust to address perceived equipoise and subsequent attrition. TRIAL REGISTRATION: Current Controlled Trials ISRCTN29874209. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 47. See the NIHR Journals Library website for further project information. PMID- 27365227 TI - How matching may impact interpretation: Comments on "A matched-cohort analysis of 192 pancreatic anaplastic carcinomas and 960 pancreatic adenocarcinomas: A 13 year North American experience using the National Cancer Data Base (NCDB)". PMID- 27365228 TI - Incidence, reasons, and risk factors for readmission after surgery for benign distal esophageal disease. AB - BACKGROUND: Our aim was to ascertain the incidence of, reasons for, and risk factors associated with hospital readmission after an operation for benign distal esophageal disease. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database (2012-2014), patients with a primary diagnosis of gastroesophageal reflux disease, paraesophageal hiatal hernia, or achalasia who underwent fundoplication, paraesophageal hernia repair, or Heller myotomy were identified. The primary outcome was hospital readmission. Multivariable logistic regression analysis was used to identify risk factors associated with hospital readmission. RESULTS: Of the 14,478 patients included in this study, 801 (5.5%) were readmitted at a median of 11 days (interquartile range 6-17) postprocedure. Intolerance of oral intake (21.8%), respiratory complications (11.6%), abdominal pain (6.0%), and venous thromboembolic events (4.7%) were some of the most common reasons for readmission. Open operative approach (odds ratio 1.34, 95% confidence interval 1.05-1.71), chronic steroid use (odds ratio 1.48, 95% confidence interval 1.10-2.00), emergency admission (odds ratio 1.50, 95% confidence interval 1.01-2.21), and predischarge complication (odds ratio 1.91, 95% confidence interval 1.42-2.59) were associated most strongly with hospital readmission. CONCLUSION: Implementing standardized perioperative strategies, such as nutritional counseling, early ambulation, intensive pulmonary toilet, and deep vein thrombosis prophylaxis, may help decrease the number of preventable readmissions and enhance the overall quality of care in this patient population. PMID- 27365229 TI - The role of the drebrin/EB3/Cdk5 pathway in dendritic spine plasticity, implications for Alzheimer's disease. AB - The drebrin/EB3/Cdk5 intracellular signalling pathway couples actin filaments to dynamic microtubules in cellular settings where cells are changing shape. The pathway has been most intensively studied in neuronal development, particularly neuritogenesis and neuronal migration, and in synaptic plasticity at dendritic spines in mature neurons. Drebrin is an actin filament side-binding and bundling protein that stabilises actin filaments. The end-binding (EB) proteins are microtubule plus-end tracking proteins (+TIPs) that localise to the growing plus ends of dynamic microtubules and regulate their behavior and the binding of other +TIP proteins. EB3 binds specifically to drebrin when drebrin is bound to actin filaments, for example at the base of a growth cone filopodium, and EB3 is located at the plus-end of a growing microtubule inserting into the filopodium. This interaction therefore forms the basis for coupling dynamic microtubules to actin filaments in growth cones of developing neurons. Appropriate responses to growth cone guidance cues depend on actin filament/microtubule co-ordination in the growth cone, although the role of the drebrin/EB3/Cdk5 pathway in this context has not been directly tested. A similar cytoskeleton coupling pathway operates in dendritic spines in mature neurons where the activity-dependent insertion of dynamic microtubules into dendritic spines is facilitated by drebrin binding to EB3. Microtubule insertion into dendritic spines drives spine maturation during long-term potentiation and therefore has a role in synaptic plasticity and memory formation. In Alzheimer's disease and related chronic neurodegenerative diseases, there is an early and dramatic loss of drebrin from dendritic spines that precedes synapse loss and neurodegeneration and might contribute to a failure of synaptic plasticity and hence to cognitive decline. PMID- 27365238 TI - Veterinary medicines update. AB - The following information has been produced for Veterinary Record by the Veterinary Medicines Directorate (VMD) to provide an update for veterinary surgeons on recent changes to marketing authorisations for veterinary medicines in the UK and on other relevant issues. PMID- 27365239 TI - Disease surveillance in England and Wales, June 2016. AB - Targeted surveillance for bluetongue virus beginsHighlights from the scanning surveillance networkUpdate on international disease threatsMonitoring of colistin resistance in pigs in scanning surveillance submissions These are among matters discussed in the Animal and Plant Health Agency's (APHA's) June disease surveillance report. PMID- 27365240 TI - Monitoring of colistin resistance in pigs in scanning surveillance submissions. AB - This article, prepared by the APHA Pig Expert Group, summarises how scanning surveillance activities have highlighted colistin resistance in pigs. PMID- 27365230 TI - Microtubules in health and degenerative disease of the nervous system. AB - Microtubules are essential for the development and maintenance of axons and dendrites throughout the life of the neuron, and are vulnerable to degradation and disorganization in a variety of neurodegenerative diseases. Microtubules, polymers of tubulin heterodimers, are intrinsically polar structures with a plus end favored for assembly and disassembly and a minus end less favored for these dynamics. In the axon, microtubules are nearly uniformly oriented with plus ends out, whereas in dendrites, microtubules have mixed orientations. Microtubules in developing neurons typically have a stable domain toward the minus end and a labile domain toward the plus end. This domain structure becomes more complex during neuronal maturation when especially stable patches of polyaminated tubulin become more prominent within the microtubule. Microtubules are the substrates for molecular motor proteins that transport cargoes toward the plus or minus end of the microtubule, with motor-driven forces also responsible for organizing microtubules into their distinctive polarity patterns in axons and dendrites. A vast array of microtubule-regulatory proteins impart direct and indirect changes upon the microtubule arrays of the neuron, and these include microtubule-severing proteins as well as proteins responsible for the stability properties of the microtubules. During neurodegenerative diseases, microtubule mass is commonly diminished, and the potential exists for corruption of the microtubule polarity patterns and microtubule-mediated transport. These ill effects may be a primary causative factor in the disease or may be secondary effects, but regardless, therapeutics capable of correcting these microtubule abnormalities have great potential to improve the status of the degenerating nervous system. PMID- 27365241 TI - Patent ductus arteriosus in cats. PMID- 27365242 TI - Transient agalactia in ewes. PMID- 27365243 TI - Effect of Brexit on EU graduates working in the UK. PMID- 27365244 TI - Elastic band injuries in cattle and sheep. PMID- 27365246 TI - BVA Members' Day heads to Bristol. AB - BVA Members' Day will be held in Bristol on September 22 at the eco-friendly @Bristol Science Centre. All BVA members are invited to join us for free. PMID- 27365245 TI - Lipid infusion in the management of poisoning. PMID- 27365247 TI - Get involved in the Young Vet Network. AB - BVA's Young Vet Network (YVN) supports members from their final year at vet school to eight years after graduation. It is during this period that graduates particularly benefit from access to peer support. Here Tim Keen, BVA marketing manager, provides an update on what's happening. PMID- 27365248 TI - Why EMS matters. AB - Becky Marr, one of the recent graduate reps on BVA Council, reminisces about her experiences of EMS and explains why EMS matters. PMID- 27365250 TI - BVA Scottish Branch AGM. AB - Ofordi Nabokei, BVA's head of policy and governance, reports from the Scottish Branch AGM. PMID- 27365249 TI - BVA and AWF hold parliamentary reception. AB - After another successful Animal Welfare Foundation (AWF) Discussion Forum, BVA honorary member Neil Parish MP hosted an evening reception in the House of Commons' terrace pavilion on behalf of BVA and AWF. Felicity Quick, BVA media officer, reports on the event. PMID- 27365251 TI - Looking to the future at BVA Congress. AB - BVA Congress is well known for tackling the big issues of the day with fantastic speakers, and this year is no different. Sally Burnell, BVA director of policy, media and strategy, sets out some of the highlights of the 2016 programme. PMID- 27365252 TI - Getting on with a PhD in a changing political landscape. AB - Myfanwy Hill wrote this on June 24, just after the result of the EU referendum was announced. Almost exactly a year after she started her PhD in Cambridge, she reflects on how far she has come and where she is going. PMID- 27365253 TI - Ten-minute chat. AB - Liz Edmondson Day is the practice manager at Stanley House Veterinary Group, which recently won the Employer of the Year category in the 2016 Pendle Business Awards, which are intended to recognise high achieving businesses in the area. PMID- 27365255 TI - Corrigendum. AB - Jenkins, C., Arulogun, O. S., Singh, A., Mande, A. T., Ajayi, E., Calys-Tagoe, B., . . . the SIREN Team (2016). Stroke Investigative Research and Education Network: Community engagement and outreach within phenomics core. Health Education & Behavior, 43(1 Suppl.), 82S-92S. (Original DOI: 10.1177/1090198116634082). PMID- 27365257 TI - Prospective Evaluation of Ultrasound Accuracy in the Detection of Pelvic Carcinomatosis in Patients with Ovarian Cancer. AB - We analyzed the accuracy of transvaginal sonography in detection of pelvic carcinomatosis in ovarian cancer patients and factors (age, body mass index, performance status, ascites, stage, histotype, tumor grade) influencing the performance of ultrasound. In this prospective study, all 191 consecutively included patients underwent a pre-operative ultrasound staging examination according to institutional protocol. Peritoneal spread was assessed on the basis of peri-operative findings or histology. The area under the receiver operating characteristic curve for the detection of carcinomatosis was 0.90 (0.84-0.93); the sensitivity was 84% (95% confidence interval [CI]: 75%-%90), specificity 96% (95% CI: 89%-99%), positive predictive value 96% (95% CI: 89%-99%), negative predictive value 83% (95% CI: 74%-90%) and overall accuracy 89% (95% CI: 84% 93%). We report that transvaginal sonography is clinically useful in the detection of pelvic carcinomatosis. PMID- 27365256 TI - Preventive aerobic training exerts a cardioprotective effect on rats treated with monocrotaline. AB - Pulmonary arterial hypertension (PAH) is a chronic disease which causes overload to the right ventricle. The effect of preventive training on cardiac remodelling in this condition is still unknown. This study aimed to evaluate the influence of preventive training on hypertrophy, heart function and gene expression of calcium transport proteins in rats with monocrotaline-induced PAH. Thirty-two male Wistar rats were randomly divided into four groups: S, sedentary control; T, trained control; SM, sedentary monocrotaline; and TM, trained monocrotaline. The preventive training protocol was performed on a treadmill for 13 weeks, five times/week. The first two weeks were adopted for adaptation to training with gradual increases in speed/time. The speed of the physical training from the third to tenth weeks was gradually increased from 0.9 to 1.1 km/h for 60 min. Next, monocrotaline was applied (60 mg/kg) to induce PAH and lactate threshold analysis performed to determine the training speeds. The training speed of the TM group in the following two weeks was 0.8 km/h for 60 min and the T = 0.9 km/h for 60 min; in the final two weeks, both groups trained at the same speed and duration 0.9 km/h, 60 min. Cardiac function was assessed through echocardiography, ventricular hypertrophy through histomorphometric analysis and gene expression through RT-qPCR. Right cardiac function assessed through the peak flow velocity was SM = 75.5 cm/s vs. TM = 92.0 cm/s (P = 0.001), and ventricular hypertrophy was SM = 106.4 MUm2 vs. TM = 77.7 MUm2 (P = 0.004). There was a decrease in the gene expression of ryanodine S = 1.12 au vs. SM = 0.60 au (P = 0.02) without alterations due to training. Thus, we conclude that prior physical training exerts a cardioprotective effect on the right ventricle in the monocrotaline rat model. PMID- 27365258 TI - Impact of Corticosteroid Injection Site on the Treatment Success Rate of Trigger Finger: A Prospective Study Comparing Ultrasound-Guided True Intra-Sheath and True Extra-Sheath Injections. AB - The aim of this study was to investigate whether differences in corticosteroid injection site influence the therapeutic effect on trigger finger and thickness of local structures such as the A1 pulley and flexor tendons. Previously untreated trigger fingers were randomly assigned to receive either a true intra sheath (group I) or an extra-sheath (group E) injection under ultrasonographic guidance. Symptom remission and recurrence rates and recurrence timing did not significantly differ between the groups. Ultrasonography revealed mean (standard deviation) pre-injection A1 pulley thicknesses of 1.1 (0.3) and 1.1 (0.2) mm in groups I and E, respectively. One month after injection, these decreased to 0.7 (0.2) and 0.8 (0.2) mm, respectively (p < 0.05). Furthermore, mean (standard) pre injection flexor digitorum tendon thickness was 4.1 (0.4) and 4.0 (0.5) mm in groups I and E, respectively, and, 1 mo after injection, decreased to 3.9 (0.3) and 3.8 (0.5) mm, respectively (p < 0.05). However, the difference at each time point between the two groups was not statistically significant. True intra-sheath injection offers no apparent advantage over extra-sheath injection for treating trigger fingers because both have the same effect on local structures. PMID- 27365259 TI - Can registry data be used as a proxy for perceived stress? A cross-sectional study. AB - PURPOSE: This study explores the applicability of registry data as a proxy for perceived stress by examining the association between perceived stress measured in health surveys and registry data. METHODS: Of 35,700 randomly invited participants from the 2010 Health Survey in the North Denmark Region (age 16-99 years), 21,842 answered 10 items from Cohen's Perceived Stress Scale. Respondents were divided into quartiles based on their stress score. Survey information was individually linked to national registries containing information on prescribed psychiatric medication and consultations with psychologists or psychiatrists from 2009 to 2011. RESULTS: The percentage of persons with prescriptions or consultations was higher (37.6%) in the highest stress score group, compared with the lowest stress score group (7.7%). Odds ratio (95% confidence interval) for the highest score compared with the lowest score was 7.3 (6.5-8.1). Different combinations of treatment showed low sensitivity (8.7%-37.6%), positive predictive value (49.4%-56.8%), and positive agreement (16.2%-42.7%) were found, whereas specificity (88.5%-98.0%) and negative agreement (85.5%-87.2%) were higher. Kappa measure showed slight to fair agreement (0.104-0.285). CONCLUSIONS: Participants reporting high perceived stress were more often prescribed medications and referred for consultations with psychologists or psychiatrists. However, due to low predictive values, registry data may not be suitable as a proxy for perceived stress. PMID- 27365260 TI - Virtual reality versus reality in post-stroke rehabilitation. PMID- 27365262 TI - Prevention of Hospital-Acquired Adverse Drug Reactions in Older People Using Screening Tool of Older Persons' Prescriptions and Screening Tool to Alert to Right Treatment Criteria: A Cluster Randomized Controlled Trial. AB - OBJECTIVES: To determine whether use of the Screening Tool of Older Persons' Prescriptions (STOPP) and Screening Tool to Alert to Right Treatment (START) criteria reduces incident hospital-acquired adverse drug reactions (ADRs), 28-day medication costs, and median length of hospital stay in older adults admitted with acute illness. DESIGN: Single-blind cluster randomized controlled trial (RCT) of unselected older adults hospitalized over a 13-month period. SETTING: Tertiary referral hospital in southern Ireland. PARTICIPANTS: Consecutively admitted individuals aged 65 and older (N = 732). INTERVENTION: Single time point presentation to attending physicians of potentially inappropriate medications according to the STOPP/START criteria. MEASUREMENTS: The primary outcome was the proportion of participants experiencing one or more ADRs during the index hospitalization. Secondary outcomes were median length of stay (LOS) and 28-day total medication cost. RESULTS: One or more ADRs occurred in 78 of the 372 control participants (21.0%; median age 78, interquartile range (IQR) 72-84) and in 42 of the 360 intervention participants (11.7%; median age 80, IQR 73-85) (absolute risk reduction = 9.3%, number needed to treat = 11). The median LOS in the hospital was 8 days (IQR 4-14 days) in both groups. At discharge, median medication cost was significantly lower in the intervention group (?73.16, IQR ?38.68-121.72) than in the control group (?90.62, IQR ?49.38-162.53) (Wilcoxon rank test Z statistic = -3.274, P < .001). CONCLUSION: Application of STOPP/START criteria resulted in significant reductions in ADR incidence and medication costs in acutely ill older adults but did not affect median LOS. PMID- 27365261 TI - Efficacy and safety of non-immersive virtual reality exercising in stroke rehabilitation (EVREST): a randomised, multicentre, single-blind, controlled trial. AB - BACKGROUND: Non-immersive virtual reality is an emerging strategy to enhance motor performance for stroke rehabilitation. There has been rapid adoption of non immersive virtual reality as a rehabilitation strategy despite the limited evidence about its safety and effectiveness. Our aim was to compare the safety and efficacy of virtual reality with recreational therapy on motor recovery in patients after an acute ischaemic stroke. METHODS: In this randomised, controlled, single-blind, parallel-group trial we enrolled adults (aged 18-85 years) who had a first-ever ischaemic stroke and a motor deficit of the upper extremity score of 3 or more (measured with the Chedoke-McMaster scale) within 3 months of randomisation from 14 in-patient stroke rehabilitation units from four countries (Canada [11], Argentina [1], Peru [1], and Thailand [1]). Participants were randomly allocated (1:1) by a computer-generated assignment at enrolment to receive a programme of structured, task-oriented, upper extremity sessions (ten sessions, 60 min each) of either non-immersive virtual reality using the Nintendo Wii gaming system (VRWii) or simple recreational activities (playing cards, bingo, Jenga, or ball game) as add-on therapies to conventional rehabilitation over a 2 week period. All investigators assessing outcomes were masked to treatment assignment. The primary outcome was upper extremity motor performance measured by total time to complete the Wolf Motor Function Test (WMFT) at the end of the 2 week intervention period, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NTC01406912. FINDINGS: The study was done between May 12, 2012, and Oct 1, 2015. We randomly assigned 141 patients: 71 received VRWii therapy and 70 received recreational activity. 121 (86%) patients (59 in the VRWii group and 62 in the recreational activity group) completed the final assessment and were included in the primary analysis. Each group improved WMFT performance time relative to baseline (decrease in median time from 43.7 s [IQR 26.1-68.0] to 29.7 s [21.4-45.2], 32.0% reduction for VRWii vs 38.0 s [IQR 28.0-64.1] to 27.1 s [21.2-45.5], 28.7% reduction for recreational activity). Mean time of conventional rehabilitation during the trial was similar between groups (VRWii, 373 min [SD 322] vs recreational activity, 397 min [345]; p=0.70) as was the total duration of study intervention (VRWii, 528 min [SD 155] vs recreational activity, 541 min [142]; p=0.60). Multivariable analysis adjusted for baseline WMFT score, age, sex, baseline Chedoke-McMaster, and stroke severity revealed no significant difference between groups in the primary outcome (adjusted mean estimate of difference in WMFT: 4.1 s, 95% CI 14.4 to 22.6). There were three serious adverse events during the trial, all deemed to be unrelated to the interventions (seizure after discharge and intracerebral haemorrhage in the recreational activity group and heart attack in the VRWii group). Overall incidences of adverse events and serious adverse events were similar between treatment groups. INTERPRETATION: In patients who had a stroke within the 3 months before enrolment and had mild-to-moderate upper extremity motor impairment, non-immersive virtual reality as an add-on therapy to conventional rehabilitation was not superior to a recreational activity intervention in improving motor function, as measured by WMFT. Our study suggests that the type of task used in motor rehabilitation post-stroke might be less relevant, as long as it is intensive enough and task-specific. Simple, low-cost, and widely available recreational activities might be as effective as innovative non-immersive virtual reality technologies. FUNDING: Heart and Stroke Foundation of Canada and Ontario Ministry of Health. PMID- 27365263 TI - A case series on the use of circumferential radiofrequency ablation for early esophageal squamous neoplasias in patients with esophageal varices. AB - BACKGROUND AND AIMS: Endoscopic radiofrequency ablation (RFA) is a rapidly evolving therapeutic modality for early esophageal squamous cell neoplasias (ESCNs). However, the feasibility of RFA for ESCNs in the setting of esophageal varices has not been reported. METHODS: We retrospectively enrolled 8 consecutive patients with cirrhosis (Child-Pugh score <=6) with early flat-type ESCNs (high grade intraepithelial neoplasia/intramucosal cancer, and Lugol unstained lesion [USL] length >=3 cm extending >=1/2 the circumference) on or adjacent to esophageal varices, for which circumferential RFA was applied as the initial treatment. The primary endpoint was a complete response at 12 months, and the secondary endpoints were adverse events and procedure-related mortality. RESULTS: The mean USL length was 5.3 cm (range, 3-10 cm), and the average length of the treatment area was 7.5 cm (range, 5-12 cm), with an average procedure time of 31.9 min (range, 25-40 min). After circumferential RFA, 3 adverse events were recorded, including 2 intramucosal hematomas and 1 mucosal laceration, all of which spontaneously resolved without further management. No massive bleeding, perforation, stricture, or hepatic failure occurred after the procedure. Six of the 8 patients achieved a complete response after single circumferential RFA, but 2 had residual squamous neoplasias. After additional focal-type RFA treatment, all achieved a complete response at 12 months. No neoplastic progression or recurrence occurred during a median follow-up period of 21.6 months (range, 13-42 months). CONCLUSIONS: RFA was associated with good treatment results, no neoplastic progression, and an acceptable adverse event profile for the treatment of early ESCNs in patients with well-compensated cirrhosis and esophageal varices. PMID- 27365264 TI - Endoscopic puncture-suture device to close gastric wall defects after full thickness resection: a porcine study. AB - BACKGROUND AND AIMS: Closure of gastric wall defects after endoscopic full thickness resection remains a clinical challenge. We aimed to introduce an endoscopic puncture-suture device (EPSD) for the closure of such defects. We evaluated the safety, efficacy, and outcomes of the EPSD for closure of gastric wall defects after endoscopic full-thickness resection (EFTR), compared with the metallic clips closure method. METHODS: Twenty-four Bama mini pigs (20-25 kg) were randomly divided into 2 groups. The EPSD was used in the experimental group and metallic clips were used in the control group. Twelve pigs were randomly assigned to each group. Six pigs underwent EFTR on the anterior wall of the gastric body, whereas the other 6 pigs underwent the same procedure on the posterior wall. The diameter of the resection margin was 2 cm. Either EPSD or metallic clips were applied to close the defects. The duration of the resection and closure, incidence of operative adverse events, and wound recovery were compared and analyzed according to the method of closure. RESULTS: For defects at the same sites, EPSD significantly reduced closure time compared with the metallic clips method (anterior wall, 8 min vs 27.5 min; posterior wall, 7.8 min vs 26.8 min). CONCLUSION: EPSD is a quick, simple, safe, and effective method to close gastric wall defects after EFTR. PMID- 27365265 TI - Long-term prognosis of expanded-indication differentiated-type early gastric cancer treated with endoscopic submucosal dissection or surgery using propensity score analysis. AB - BACKGROUND AND AIMS: Although endoscopic submucosal dissection (ESD) for expanded indication lesions of differentiated-type early gastric cancer (EGC) has been widely accepted, no prospective randomized study has been conducted on this subject. This study aimed to evaluate the long-term outcomes of ESD and surgery for expanded-indication lesions of differentiated-type EGC. METHODS: Between 1997 and 2012, 1500 consecutive patients with EGC were treated in Osaka City University Hospital. Using propensity score matching and inverse probability of treatment weighting (IPTW), we retrospectively evaluated the long-term outcomes, risk factors for mortality, and adverse events for patients with expanded indication lesions of differentiated-type EGC who underwent ESD or surgical treatments. RESULTS: A total of 308 patients with expanded-indication lesions of differentiated-type EGC confirmed by pathologic examination after ESD or surgery met the eligibility criteria. After matching, the 5-year overall survival rate was higher in the ESD group than in the surgery group (97.1% vs 85.8%; P = .01). We also found that surgery was significantly associated with mortality using both the IPTW method (hazard ratio [HR], 10.89; 95% confidence interval [CI], 1.37 86.6; P < .01), and Cox analysis (HR, 8.60; 95% CI, 1.11-66.52; P = .04) after matching. Significantly fewer adverse events were associated with ESD than with surgery (6.8% vs 28.4%; P < .01). No cause-specific mortality was observed in either group. CONCLUSIONS: Our results indicate that ESD might be an alternative treatment modality for expanded-indication lesions of differentiated-type EGC. PMID- 27365266 TI - Triolimus: A Multi-Drug Loaded Polymeric Micelle Containing Paclitaxel, 17-AAG, and Rapamycin as a Novel Radiosensitizer. AB - Triolimus is a multi-drug loaded polymeric micelle containing paclitaxel (PTX), 17-allylamino-17-demethoxygeldanamycin (17-AAG), and rapamycin (RAP). This study examines the radiosensitizing effect of Triolimus in vitro and in vivo. Radiosensitizing effects of Triolimus on A549 cells are dose dependent and at 2 * 10-9 m, Triolimus shows significant radiosensitization even at low radiation doses (2 Gy). By sensitivity enhancement ratio, PTX alone, dual drug combinations, and Triolimus treatment at 2 * 10-9 m have radiosensitizing effects with potency as follows: PTX alone (PTX) > PTX and RAP (P/R) > Triolimus (TRIO) > PTX and 17-AAG (P/17) >17-AAG and RAP (17/R). In vivo, fractionated radiation of 15 Gy preceded by infusion of PTX alone, dual drug combinations, or an intermediate dose of Triolimus (Int. TRIO: PTX/17-AAG/RAP at 15/15/7.5 mg kg-1 ) strongly inhibits A549 tumor growth. Notably, pretreatment with high dose of Triolimus (High TRIO: PTX/17-AAG/RAP at 60/60/30 mg kg-1 ) before the fractionated radiation leads to tumor control for up to 24 weeks. An enhanced radiosensitizing effect is observed without an increase in acute toxicity compared to PTX alone or radiation alone. These results suggest that further investigations of Triolimus in combination with radiation therapy are merited. PMID- 27365268 TI - Vascular accident code: A security system in massive bleeding in laparoscopic urologic surgery. PMID- 27365267 TI - Comparative study of multiport laparoscopy and umbilical laparoendoscopic single site surgery with reusable platform for treating renal masses. AB - INTRODUCTION: Umbilical laparoendoscopic single-site (LESS) surgery is an increasingly used modality for treating renal masses. We present a prospective comparison between LESS renal surgery and conventional laparoscopy. MATERIAL AND METHOD: A comparative paired study was conducted that evaluated the surgical results and complications of patients with renal neoplasia treated with LESS surgery (n=49) or multiport laparoscopy (n=53). The LESS approach was performed with reusable material placed in the navel and double-rotation curved instruments. An additional 3.5-mm port was employed in 69.4% of the cases. We assessed demographic data, the type of technique (nephrectomy, partial nephrectomy and nephroureterectomy), surgical time, blood loss, haemoglobin, need for transfusion, number and severity of complications (Clavien-Dindo), hospital stay, histological data and prognosis. RESULTS: There were no differences in follow-up, age, sex, body mass index, preoperative haemoglobin levels or type of surgery. Conversion occurred in 2 cases (1 in each group). The surgical time was equivalent (P=.6). Intraoperative transfusion (P=.03) and blood loss (P<.0001) was lower with LESS, postoperative haemoglobin levels were higher (P<.0001) and haemostatic agents were used more frequently (P<.0001). There were no differences in the number (P=.6) or severity (P=.47) of complications. The length of stay (P<.0001), the proportion of patients with drainage (P=.04) and the number of days with drainage (P=.0004) were lower in LESS. Twenty-five percent of the lesions operated on with LESS were benign, but the mean size was similar in the 2 groups (P=.5). Tumour recurrence and/or progression were more frequent in multiport laparoscopy (P=.0013). CONCLUSIONS: Umbilical LESS surgery with reusable platform enables various surgical techniques to be performed when treating renal masses, with time consumption and safety comparable to conventional laparoscopy. The LESS approach is advantageous in terms of blood loss and hospital stay. PMID- 27365269 TI - [Lung neuroendocrine large cell carcinoma in young women. An unusual presentation]. AB - INTRODUCTION: Lung neuroendocrine large cell carcinoma is a rare tumor with a poor prognosis. There are very few guidelines for treating this cancer but a better knowledge of its markers could improve the treatment and the prognosis. OBSERVATIONS: We report two patients who presented initially with an early stage carcinoid tumor treated with surgery. Both patients had further new neuroendocrine disease diagnosed because of intermittent carcinoid syndrome, predominantly occurring at the same time as menstruation. They were then diagnosed with metastatic lung neuroendocrine large cell carcinoma and treated with first-line cisplatin-etoposide and second-line octreotide with estrogen plus progestin. They both had a good prognosis with no disease progression to date. CONCLUSIONS: The clinical characteristics of these cases raise several questions about the pathophysiology of lung neuroendocrine large cell carcinoma and may suggest potential new treatment options. The unusual clinical presentation and good prognosis may be explained either by the second-line treatment choice or by potential molecular or hormonal biomarkers. There is a need to investigate these potential biomarkers further since they could be new therapeutic targets. PMID- 27365270 TI - ? PMID- 27365271 TI - Drug repositioning approaches to parasitic diseases: a medicinal chemistry perspective. AB - Identifying new indications for clinically useful drugs is a worthwhile approach for neglected tropical diseases. The number of successful repurposing cases in the field is growing as not-for-profit organizations, in association with academia and pharmaceutical companies, enable screening campaigns for the identification of new repositioning candidates. Current programs have delivered encouraging results as the use of state-of-the-art technologies, such as genomic and structural biology tools, and high-throughput screening platforms have become increasingly common in infectious disease research. Drug repositioning has played a key part in improving the lives of those suffering from these conditions, as evidenced by successful precedents and recent studies on preeminent parasitic disorders. PMID- 27365272 TI - Bacoside-A, an anti-amyloid natural substance, inhibits membrane disruption by the amyloidogenic determinant of prion protein through accelerating fibril formation. AB - Bacosides, class of compounds extracted from the Bacopa monniera plant, exhibit interesting therapeutic properties, particularly enhancing cognitive functions and putative anti-amyloid activity. We show that bacoside-A exerted significant effects upon fibrillation and membrane interactions of the amyloidogenic fragment of the prion protein [PrP(106-126)]. Specifically, when co-incubated with PrP(106 126), bacoside-A accelerated fibril formation in the presence of lipid bilayers and in parallel inhibited bilayer interactions of the peptide aggregates formed in solution. These interesting phenomena were studied by spectroscopic and microscopic techniques, which suggest that bacoside A-promoted fibrillation reduced the concentration of membrane-active pre-fibrillar species of the prion fragment. This study suggests that induction of fibril formation and corresponding inhibition of membrane interactions are likely the underlying factors for ameliorating amyloid protein toxicity by bacoside-A. PMID- 27365273 TI - Chemical features of in use and in progress chelators for iron overload. AB - An excessive amount of iron may become extremely toxic both for its ability to generate reactive oxygen species, and for the lack of regulatory mechanisms for iron excretion in humans. Chelation therapy has been introduced in clinical practice in the 1970's to defend thalassemia patients from the effects of iron overload and it has dramatically changed both life expectancy and quality of life. The disadvantages of the drugs in clinical use make the research for new, more suitable iron chelating agents, urgent. This review defines the requirements of an iron chelator, then points out the principal chemical features of the iron chelators in use. Finally, a survey on the last ten years of the literature relative to iron chelators is done, and the most interesting ligands are presented, with particular emphasis to those that reached clinical trials. PMID- 27365274 TI - Response to: Uveitis due to bisphosphonates: A rare side effect? PMID- 27365275 TI - Hindfoot pain: Baxter neuropathy. PMID- 27365276 TI - A case report of pseudoxanthoma elasticum and systemic lupus erythematosus: An uncommon association? PMID- 27365278 TI - Abstracts from the International Patellofemoral Pain Resesarch Retreat. PMID- 27365277 TI - Patellofemoral pain during adolescence: much more prevalent than appreciated. PMID- 27365279 TI - Leukocytoclastic vasculitis related to cocaine-adulterated levamisole. PMID- 27365280 TI - Spectroscopic characterization of genotoxic chromium(V) peptide complexes: Oxidation of Chromium(III) triglycine, tetraglycine and pentaglycine complexes. AB - Evidence is growing that metabolites of Cr(III) dietary supplements are partially oxidized to carcinogenic Cr(VI) and Cr(V) in vivo. Hence, we examined oxidations of Cr(III) peptide (triglycine, tetraglycine and pentaglycine) complexes to Cr(VI) and Cr(V) by PbO2 at 37 degrees C and physiological pH values between 3.85 and 7.4. The products were characterized by EPR and UV/Vis spectroscopies and electrospray mass spectrometry. At pH3.85, the monomeric Cr(V) complexes produced were relatively unstable and degraded over min to hr under the acidic conditions. The triglycine and tetraglycine Cr(V) complexes had five-line 14N-superhyperfine coupled EPR signals; giso, (AN) values 1.9824 (2.44*10-4cm-1) and 1.9825 (2.43*10 4cm-1), respectively. The pentaglycine Cr(V) complex had a seven-line 14N superhyperfine-coupled EPR signal: giso=1.9844; AN=2.27*10-4cm-1. In phosphate buffer (pH7.4 and 5.85), several Cr(V) intermediates were produced, but Cr(VI) was the end product. For the triglycine, tetraglycine and pentaglycine Cr(V) complexes, the giso (AN, 10-4cm-1) values were 1.9831 (2.17), 1.9843 (2.27) and 1.9844 (2.30), respectively. A second EPR signal with unresolved superhyperfine structure was observed at giso~1.966. At 1min, the tetraglycine and pentaglycine Cr(V) complexes, had another signal at giso~1.978, which decayed relative to the other signals with time. This chemistry has relevance to: (i) certain types of DNA damage produced by Cr carcinogens; (ii) the intracellular oxidation of Cr(III) to Cr(VI); and (iii) redox recycling of Cr(III) metabolites formed from both the intracellular reduction of carcinogenic Cr(VI) and from Cr(III) supplements. PMID- 27365281 TI - Regional activation within the vastus medialis in stimulated and voluntary contractions. AB - This study examined the contribution of muscle fiber orientation at different knee angles to regional activation identified with high-density surface electromyography (HDsEMG). Monopolar HDsEMG signals were collected using a grid of 13 * 5 electrodes placed over the vastus medialis (VM). Intramuscular electrical stimulation was used to selectively activate two regions within VM. The distribution of EMG responses to stimulation was obtained by calculating the amplitude of the compound action potential for each channel; the position of the peak amplitude was tracked across knee angles to describe shifts of the active muscle regions under the electrodes. In a separate experiment, regional activation was investigated in 10 knee flexion-extension movements against a fixed resistance. Intramuscular stimulation of different VM regions resulted in clear differences in amplitude distribution along the columns of the electrode grid (P < 0.001); changes in knee angle resulted in consistent shifts along the rows (P < 0.01) and negligible shifts along the columns of the electrode grid. Regional VM activation was identified in dynamic movement, with distal shifts of the EMG distribution in the eccentric phase of the movement (P < 0.05) and at more flexed knee angles (P < 0.05). HDsEMG was used to describe regional activation across the VM that was not attributable to anatomic factors. Changes in muscle fiber orientation associated with knee joint angle mainly influence the amplitude distribution along the fiber direction. Future studies are needed to understand possible functional roles for regional activation within the VM in dynamic tasks. PMID- 27365282 TI - Effect of 23-day muscle disuse on sarcoplasmic reticulum Ca2+ properties and contractility in human type I and type II skeletal muscle fibers. AB - Inactivity negatively impacts on skeletal muscle function mainly through muscle atrophy. However, recent evidence suggests that the quality of individual muscle fibers is also altered. This study examined the effects of 23 days of unilateral lower limb suspension (ULLS) on specific force and sarcoplasmic reticulum (SR) Ca(2+) content in individual skinned muscle fibers. Muscle biopsies of the vastus lateralis were taken from six young healthy adults prior to and following ULLS. After disuse, the endogenous SR Ca(2+) content was ~8% lower in type I fibers and maximal SR Ca(2+) capacity was lower in both type I and type II fibers (-11 and 5%, respectively). The specific force, measured in single skinned fibers from three subjects, decreased significantly after ULLS in type II fibers (-23%) but not in type I fibers (-9%). Western blot analyses showed no significant change in the amounts of myosin heavy chain (MHC) I and MHC IIa following the disuse, whereas the amounts of sarco(endo)plasmic reticulum Ca(2+)-ATPase 1 (SERCA1) and calsequestrin increased by ~120 and ~20%, respectively, and the amount of troponin I decreased by ~21%. These findings suggest that the decline in force and power occurring with muscle disuse is likely to be exacerbated in part by reductions in maximum specific force in type II fibers, and in the amount of releasable SR Ca(2+) in both fiber types, the latter not being attributable to a reduced calsequestrin level. Furthermore, the ~3-wk disuse in human elicits change in SR properties, in particular a more than twofold upregulation in SERCA1 density, before any fiber-type shift. PMID- 27365283 TI - A methodological approach for quantifying and characterizing the stability of agitated saline contrast: implications for quantifying intrapulmonary shunt. AB - Agitated saline contrast echocardiography is often used to determine blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA). We applied indicator dilution theory to time-acoustic intensity curves obtained from a bolus injection of hand-agitated saline contrast to acquire a quantitative index of contrast mass. Using this methodology and an in vitro model of the pulmonary circulation, the purpose of this study was to determine the effect of transit time and gas composition [air vs. sulphur hexafluoride (SF6)] on contrast conservation between two detection sites separated by a convoluted network of vessels. We hypothesized that the contrast lost between the detection sites would increase with transit times and be reduced by using contrast bubbles composed of SF6 Changing the flow and/or reducing the volume of the circulatory network manipulated transit time. Contrast conservation was measured as the ratio of outflow and inflow contrast masses. For air, 53.2 +/- 3.4% (SE) of contrast was conserved at a transit time of 9.25 +/- 0.02 s but dropped to 16.0 +/- 1.0% at a transit time of 10.17 +/- 0.06 s. Compared with air, SF6 contrast conservation was significantly greater (P < 0.05) with 114.3 +/- 2.9% and 73.7 +/- 3.3% of contrast conserved at a transit time of 10.39 +/- 0.02 s and 13.46 +/- 0.04 s, respectively. In summary, time acoustic intensity curves can quantify agitated saline contrast, but loss of contrast due to bubble dissolution makes measuring QIPAVA across varying transit time difficult. Agitated saline composed of SF6 is stabilized and may be a suitable alternative for QIPAVA measurement. PMID- 27365284 TI - Sex Differences in Weight Loss among Veterans with Serious Mental Illness: Observational Study of a National Weight Management Program. AB - PURPOSE: Obesity disproportionately burdens individuals with serious mental illness (SMI), especially women. This observational study investigated whether there were sex differences in weight loss and program participation among veterans with SMI enrolled in the Veterans Health Administration's (VHA) MOVE! weight management program. PROCEDURES: Participants were identified from a national cohort of 148,254 veterans enrolled in MOVE! during fiscal years 2008 through 2012 who attended two or more sessions within 12 months of enrollment. The cohort included those with International Classification of Disease, 9th Edition, Clinical Modification (ICD-9-CM) diagnoses for SMI, age less than 70 years, and weight data at baseline and one or more follow-up timepoints within approximately 1 year of enrollment (n = 8,943 men; n = 2,245 women). Linear mixed models assessed associations of sex with 6- and 12-month weight change from baseline, adjusting for demographic- and site-level variables. FINDINGS: Both sexes averaged 6.4 (standard deviation, 4.6) sessions within 12 months; however, women with and without SMI participated at rates double their respective proportion rates among all VHA users. Participants averaged statistically significant weight loss at 6 months (men, -2.5 lb [95% CI, -2.8 to -2.1]; women, 2.4 lb [95% CI, -3.1 to -1.7]) and 12 months (men, -2.5 lb [95% CI, -2.8 to 2.2]; women, -2.9 lb [95% CI, -3.6 to -2.2]), but no sex-based difference in absolute weight loss at either timepoint. Slightly more women achieved 5% or greater (clinically significant) weight loss at the 12-month follow-up than did men (25.7% vs. 23.0%; p < .05). CONCLUSIONS: Women with SMI participated in MOVE! at rates equivalent to or greater than men with SMI, with comparable weight loss. More women were Black, single, had bipolar and posttraumatic stress disorder, and higher service-connected disability, suggesting areas for program customization. PMID- 27365285 TI - Using the Consolidated Framework for Implementation Research to Increase Provider Screening for Intimate Partner Violence in Rural Health Clinics. AB - PURPOSE: To demonstrate the utility of the Consolidated Framework for Implementation Research as a tool for conceptualizing and overcoming obstacles to the implementation of universal screening practices for intimate partner violence (IPV), with a particular focus on rural family practice settings. This article uses data from a 2014 statewide survey of rural primary care providers to identify potential leverage points for policy and practice changes. METHODS: The Physician Readiness to Manage Intimate Partner Violence was administered to 134 physicians and nurses at rural health clinics in a Midwestern state. Six scales measuring knowledge, attitudes, and behaviors were computed and analyzed with bivariate and logistic regression models to ascertain links between knowledge/attitudes and screening/response behaviors. FINDINGS: Knowledge and attitudes did not predict screening; rather, the number of hours of previous training on abuse and the organizational protocols of the clinics where providers were employed significantly increased the likelihood of frequent IPV screening. CONCLUSIONS: Guided by Consolidated Framework for Implementation Research principles, the author concludes that external factors, that is, state or national policies mandating IPV screening in clinics, may be an effective way to increase provider identification of a major public health problem affecting women. Rural women may benefit especially from IPV screening during health care encounters, because there are few other supportive services for abuse survivors in rural areas. PMID- 27365286 TI - Use of Hematopoietic Growth Factors and Risk of Thromboembolic and Pulmonary Toxicities in Elderly Patients with Advanced Ovarian Cancer. AB - OBJECTIVE: To evaluate the risk of thromboembolic and pulmonary toxicities associated with hematopoietic growth factor (HGF) use (i.e., erythropoietin stimulating agent [ESA] and/or colony-stimulating factor [CSF]) in a community dwelling cohort of elderly patients with advanced ovarian cancer. METHODS: We studied 8,188 women, 65 years and older from the Surveillance, Epidemiology and End Results-Medicare linked database, diagnosed from January 1, 2000 to December 31, 2009. Patients were categorized into five groups: no chemotherapy and no ESA/CSF (n = 2,616), chemotherapy but no ESA/CSF (n = 1,854), ESA only (n = 1,313), CSF only (n = 743), and ESA + CSF (n = 1,662). We reported the cumulative incidence of toxicities for 2, 6, and greater than 6 months, and the incidence density for the overall follow-up. Cox-proportional hazards regression was performed to determine risk of toxicities. RESULTS: Of the 5,572 patients receiving chemotherapy, 66.7% (n = 3,718) received HGF supportive treatment, 29.8% received ESA + CSF, 23.6% received ESA only, and 13.3% received CSF only. Patients who received chemotherapy and also ESA + CSF had a 14.1% cumulative incidence of thromboembolic event (TEE) at 6 months of follow-up compared with 8.0% in those who received chemotherapy without growth factor and 3.2% in those with neither chemotherapy nor growth factor. Those with chemotherapy who received ESA + CSF had a significantly higher risk of TEE (adjusted hazard ratio, 1.22; 95% confidence interval, 1.01-1.47) as compared with patients with chemotherapy and no ESA/CSF, although patients aged 85 years and older may experience up to a five-fold increased risk. The risk of pulmonary toxicities did not significantly differ by HGF use. CONCLUSIONS: An increased risk of TEEs was observed in elderly patients with ovarian cancer who received ESA + CSF. The risk-benefit ratio for administering HGF should be carefully evaluated, especially among those 85 years and older. PMID- 27365288 TI - Locally advanced head and neck cancer in either the older or the vulnerable adult: Making the case for a team-based, "gero-centric" approach. AB - Multidisciplinary, team-based care goes hand in hand with geriatric oncology paradigms for caring for older adults with cancer. Team-based care was the central theme for the 2015 SIOG Annual Meeting. Team-based approaches to the evaluation and management of older adults with different cancer types, including head and neck cancer, were presented. This review aims to summarize the salient points of that presentation, including a synthesis of recent multidisciplinary, "gero-centric" research efforts to improve the care for older adults with more advanced stages of head and neck cancer. PMID- 27365287 TI - Role of Marital Status in the Association between Prepregnancy Body Mass Index and Breastfeeding Duration. AB - BACKGROUND: In the United States, breastfeeding rates fail to meet national guidelines. Given the rising prevalence of obesity and births to unmarried women, this study explores if the association between prepregnancy body mass index (BMI) and breastfeeding duration differs by marital status. METHODS: Data from the 2009 2011 Pregnancy Assessment Monitoring System were analyzed. The sample included women who had live singleton births in the United States and who reported information to calculate BMI and breastfeeding duration (n = 93,106). Breastfeeding duration was categorized as never breastfed, breastfed for 8 weeks or less, and breastfed for more than 8 weeks. BMI was categorized as underweight (<18.5 kg/m(2)), normal weight (18.5-24.9 kg/m(2)), overweight (25.0-29.9 (kg/m(2)), or obese (30.0 + kg/m(2)). Marital status was categorized as married or not married. There was a significant interaction between marital status and prepregnancy BMI (p = .028). Data were stratified by marital status and multinomial logistic regression was conducted adjusting for confounding factors. RESULTS: Approximately one-half of women were of normal weight before pregnancy (50.4%); 24.1% were overweight, 21.2% were obese, and 4.3% were underweight. Among married women, the odds of never breastfeeding and breastfeeding for 8 weeks or less was greater among overweight (adjusted odds ratio [AOR], 1.23 [95% confidence interval {CI}, 1.10-1.38]; AOR, 1.36 [95% CI, 1.24-1.49]) and obese women (AOR, 1.72 [95% CI, 1.53-1.93]; AOR, 1.95 [95% CI, 1.77-2.15]) compared with normal weight women who breastfed for more than 8 weeks. In contrast, among unmarried women, no association was observed among overweight women and the association was attenuated among obese women (AOR, 1.38 [95% CI, 1.21-1.58]; AOR, 1.43 [95% CI, 1.27-1.62]). CONCLUSION: Providers and public health practitioners should be aware of the influence of marital status in the association between prepregnancy BMI and breastfeeding duration. The role of obesity and marital status should be considered in designing breastfeeding promotion interventions. PMID- 27365289 TI - Fetal and neonatal outcomes after term and preterm delivery following betamethasone administration in twin pregnancies. AB - OBJECTIVE: To investigate effects of betamethasone on fetal growth and neonatal outcomes in twins. METHODS: A retrospective cohort study was conducted of twins delivered at one center in Berlin, Germany, between 1993 and 2011. The betamethasone group included twin pregnancies with preterm labor, cervical shortening, preterm premature rupture of membranes, or vaginal bleeding, and exposure to betamethasone between 23(+5) and 33(+6) weeks. The control group included twin pregnancies with no betamethasone exposure matched for length at delivery. Fetal growth and neonatal anthropometric data were analyzed by twin pair structure, dose, and gestational age (linear mixed model). RESULTS: Overall, 1922 live-born twin pairs (653 betamethasone group, 1269 controls) were included. Compared with controls, late-preterm twins exposed to betamethasone were lighter (mean difference -126g), had a smaller head circumference (-0.4cm), and a shorter body length (-0.8cm) after adjustment for confounders (P<0.05). Female neonates from mixed or same-sex twin pairs had a lower birth weight than controls (betamethasone <=16mg: -114g; betamethasone 24mg: -124g; betamethasone >24mg: 187g), with no detectable improvement in neonatal morbidity (hyperbilirubinemia, respiratory distress, asphyxia) or mortality. CONCLUSION: Betamethasone reduced birth weight, head circumference, and length of female preterm neonates in twin pairs in a dose-dependent manner. The neonatal mortality and morbidity were not improved by betamethasone. PMID- 27365290 TI - A retrospective study of HIV, antiretroviral therapy, and pregnancy-associated hypertension among women in Lusaka, Zambia. AB - OBJECTIVE: To investigate the association between HIV, antiretroviral therapy (ART), and pregnancy-associated hypertension (PAH) in an HIV-endemic setting. METHODS: A retrospective cohort study was undertaken of pregnant women for whom information was recorded between February 2006 and December 2012 in the Zambia Electronic Perinatal Record System, which captures data from 25 facilities in Lusaka, Zambia. PAH was defined as eclampsia, pre-eclampsia, hypertension, or elevated blood pressure (>140/80mm Hg) during delivery admission. Logistic regression estimated the odds of PAH among women by HIV serostatus, and by most recent CD4 T lymphocyte count and ART status among women with HIV infection. RESULTS: Among 249 771 women included in the analysis, 5354 (2.1%) had PAH. Compared with women without HIV infection, women with HIV infection not receiving ART had lower odds of PAH (adjusted odds ratio [AOR] 0.86, 95% confidence interval 0.78-0.95), whereas those with HIV infection who had initiated ART had higher odds of PAH (AOR 1.15, 95% CI 1.01-1.32). No association was found between PAH and timing of ART initiation or CD4 lymphocyte count. CONCLUSION: In a large African urban cohort, women with untreated HIV infection had the lowest odds of PAH. Treatment with ART could increase PAH risk beyond that of women without HIV infection and those with untreated infection. PMID- 27365291 TI - Predictors and outcomes of low birth weight in Lusaka, Zambia. AB - OBJECTIVE: To determine factors associated with low birth weight (LBW) in an urban Zambian cohort and investigate risk of adverse outcomes for LBW neonates. METHODS: The present retrospective cohort analysis used data recorded between February 2006 and December 2012 for singletons and first-born twins delivered in the public health system of Lusaka, Zambia. Routine clinical data and generalized estimating equations were used to examine covariates associated with LBW (<2500 g) and describe outcomes of LBW. RESULTS: In total, 200 557 neonates were included, 21 125 (10.5%) of whom were LBW. Placental abruption, delivery before 37 weeks, and twin pregnancy were associated with LBW in multivariable analysis (P<0.01 for all). Compared with neonates weighing more than 2500 g, LBW neonates were at higher risk of stillbirth (adjusted odds ratio [AOR] 8.6, 95% confidence interval [CI] 6.5-11.5), low Apgar score (AOR 5.7, 95% CI 4.6-7.2), admission to the neonatal intensive care unit (AOR 5.4, 95% CI 3.5-8.3), and very early neonatal death (AOR 6.2, 95% CI 3.7-10.3). CONCLUSION: LBW neonates are at increased risk of adverse outcomes, including stillbirth and neonatal death, independent of pregnancy duration at delivery and multiple pregnancy. These findings underscore the need for early, comprehensive, and high-quality prenatal care. PMID- 27365292 TI - Middle paleolithic human deciduous incisor from Grotta del Cavallo, Italy. AB - OBJECTIVES: In this contribution, we present a morphological description and comparative morphometric analysis of Cavallo D, a human tooth unearthed from the Mousterian FIII sublayer of Grotta del Cavallo (Apulia, Italy). MATERIALS AND METHODS: We used microCT data to provide a detailed morphological description and morphometric analysis of the Cavallo D human tooth based on traditional diameter measurements and 3D enamel thickness. Moreover, new AMS radiocarbon dating of charcoals from layers FII was carried out. RESULTS: Morphological features observed in Cavallo D align the tooth to Neandertals. Similarly, the large size of the tooth (e.g., BL diameter) and the relatively thinner enamel thickness are typical Neandertal traits. 14 C datings of layer FII attribute the tooth to a time range of 45,600-42,900 cal BP (at 68% level of probability). DISCUSSION: Up to now, the Rdi1 Cavallo D represents the most recent Neandertal human remain in southern Italy related to a radiocarbon dated stratigraphy. Moreover, since deciduous teeth have been less investigated than the permanent ones, this contribution brings new data to increase our knowledge on the variability of the Neandertal deciduous dentition. PMID- 27365293 TI - The Exonuclease Trex2 Shapes Psoriatic Phenotype. AB - Trex2 is a keratinocyte-specific 3'-deoxyribonuclease that participates in the maintenance of skin homeostasis after DNA damage. Here, we show that this exonuclease is strongly upregulated in human psoriasis, a hyperproliferative and inflammatory skin disease. Similarly, the imiquimod (IMQ)- and Il23-induced mouse psoriasis was associated with a substantial upregulation of Trex2, which was recruited into fragmented chromatin in keratinocytes that were undergoing impaired proliferation, differentiation, and cell death, indicating an important role in DNA processing. Using Trex2 knockout mice, we have found that Trex2 deficiency attenuated IMQ-induced psoriasis-like skin inflammation and enhanced IMQ-induced parakeratosis. Also, Il23-induced ear swelling was diminished in Trex2 knockout mice in comparison with wild-type (wt) mice. Transcriptome analysis identified multiple genes that were deregulated by Trex2 loss after treatment with IMQ. Specifically, immune response genes and pathways normally associated with inflammation were downregulated, whereas those related to skin differentiation and chromatin biology showed increased expression. Interestingly, Trex2 deficiency led to decreased IMQ-induced keratinocyte death via both cell autonomous and noncell autonomous mechanisms. Hence, our data indicate that Trex2 acts as a critical factor in the pathogenesis of psoriasis by promoting keratinocyte apoptosis and enucleation and thereby influencing skin immune responses. PMID- 27365294 TI - A Randomized, Clinical Trial of Preadmission Chlorhexidine Skin Preparation for Lower Extremity Total Joint Arthroplasty. AB - BACKGROUND: Periprosthetic infections are devastating postoperative complications of total joint arthroplasty (TJA), with native skin flora commonly identified as causative organisms. We compared 2% chlorhexidine gluconate-impregnated cloths to standard-of-care antiseptic bathing in patients before TJA, to evaluate periprosthetic infection risk at 1-year follow-up. METHODS: This was a prospective, randomized, controlled trial at a single institution of patients undergoing hip or knee arthroplasty. Chlorhexidine-treated patients (275 arthroplasties) applied 2% chlorhexidine gluconate-impregnated cloths the night before and morning of admission. The standard-of-care cohort (279 arthroplasties) bathed with soap and water preadmission. Patients were excluded according to the following: (1) unable to comply with study requirements, (2) pregnant, (3) <18 years, (4) medical history of immunosuppression or steroid use, (5) chronic hepatitis B/C infection, (6) had infection around joint requiring surgery, or (7) chose not to participate. A total of 539 patients (554 arthroplasties) were included in the final population. There were no significant differences in American Society of Anesthesiologists grade, cut time, risk scores, or diabetes and smoking prevalence between cohorts (P > .05). RESULTS: A lower periprosthetic infection rate was found in the chlorhexidine cohort (0.4%) when compared to standard-of-care cohorts (2.9%). The infection odds ratio was 8.15 (95% confidence interval = 1.01-65.6; P = .049) for the standard-of-care cohort compared to the chlorhexidine cohort. No differences in assessed risk factors were found between groups. No severe adverse events were observed. CONCLUSIONS: Preoperative chlorhexidine cloth use decreased the risk of periprosthetic infection. This may be an appropriate antiseptic protocol to implement for patients undergoing lower extremity TJA. PMID- 27365295 TI - Technical Considerations and Accuracy Improvement of Accelerometer-Based Portable Computer Navigation for Performing Distal Femoral Resection in Total Knee Arthroplasty. AB - BACKGROUND: Accelerometer-based computer navigation has been shown to be highly accurate for performing distal femoral and proximal tibial component alignment in total knee arthroplasty (TKA), although the procedure for the femoral component is less accurate than for the tibial component. METHODS: First, 30 knees without hip osteoarthritis or proximal femoral surgeries were selected. Sequential hip adduction, abduction, and flexion were performed, and the femoral head was monitored fluoroscopically in the coronal plane before TKA. Significantly more movement was detected during hip adduction than during abduction and flexion. Then, postoperative femoral and tibial component alignment was retrospectively evaluated in 48 TKAs before fluoroscopic monitoring (early group) and in the next 61 TKAs with femoral registration using smaller adduction movements to avoid large femoral head movements (later group). Another 47 TKAs treated with the conventional intramedullary method for the distal femoral component and the extramedullary method for the proximal tibial component were also analyzed (IM and EM group) for historic control. RESULTS: Significantly large variances in the femoral component implantation of the early group were detected in both the coronal and sagittal planes. The sagittal femoral implantation angle of the early group (4.6 +/- 3.0 degrees ) was significantly larger than that of the later group (3.2 +/- 1.8 degrees ) when 3.5 degrees was the target for both groups. No significant difference was detected in the variances of either the coronal or sagittal tibial component implantation, although the coronal tibial implantation angle was significantly smaller (-1.3 +/- 1.3 degrees valgus) in the early group than in the other groups. CONCLUSION: Accelerometer-based navigation sometimes has technical issues during registration associated with hip adduction. We showed that femoral registration without large adduction movements will enable more accurate femoral implantation. Surgeons should also keep in mind that the coronal tibial component is likely to be in valgus alignment (about 1 degrees ) even if a neutral angle (0 degrees ) is selected with this particular device. PMID- 27365296 TI - Dopamine is Required for Activity-Dependent Amplification of Arc mRNA in Developing Postnatal Frontal Cortex. AB - The activity-regulated gene Arc/Arg3.1 encodes a postsynaptic protein crucially involved in glutamatergic synaptic plasticity. Genetic mutations in Arc pathway and altered Arc expression in human frontal cortex have been associated with schizophrenia. Although Arc expression has been reported to vary with age, what mechanisms regulate Arc mRNA levels in frontal cortex during postnatal development remains unclear. Using quantitative mRNA analysis of mouse frontal cortical tissues, we mapped the developmental profiles of Arc expression and found that its mRNA levels are sharply amplified near the end of the second postnatal week, when mouse pups open their eyes for the first time after birth. Surprisingly, electrical stimulation of the frontal cortex before eye-opening is not sufficient to drive the amplification of Arc mRNA. Instead, this amplification needs both electrical stimulation and dopamine D1-type receptor (D1R) activation. Furthermore, visual stimuli-driven amplification of Arc mRNA is also dependent on D1R activation and dopamine neurons located in the ventral midbrain. These results indicate that dopamine is required to drive activity dependent amplification of Arc mRNA in the developing postnatal frontal cortex and suggest that joint electrical and dopaminergic activation is essential to establish the normal expression pattern of a schizophrenia-associated gene during frontal cortical development. PMID- 27365297 TI - Words in Context: The Effects of Length, Frequency, and Predictability on Brain Responses During Natural Reading. AB - Word length, frequency, and predictability count among the most influential variables during reading. Their effects are well-documented in eye movement studies, but pertinent evidence from neuroimaging primarily stem from single-word presentations. We investigated the effects of these variables during reading of whole sentences with simultaneous eye-tracking and functional magnetic resonance imaging (fixation-related fMRI). Increasing word length was associated with increasing activation in occipital areas linked to visual analysis. Additionally, length elicited a U-shaped modulation (i.e., least activation for medium-length words) within a brain stem region presumably linked to eye movement control. These effects, however, were diminished when accounting for multiple fixation cases. Increasing frequency was associated with decreasing activation within left inferior frontal, superior parietal, and occipito-temporal regions. The function of the latter region-hosting the putative visual word form area-was originally considered as limited to sublexical processing. An exploratory analysis revealed that increasing predictability was associated with decreasing activation within middle temporal and inferior frontal regions previously implicated in memory access and unification. The findings are discussed with regard to their correspondence with findings from single-word presentations and with regard to neurocognitive models of visual word recognition, semantic processing, and eye movement control during reading. PMID- 27365299 TI - Dynamic Changes in Cortical Effective Connectivity Underlie Transsaccadic Integration in Humans. AB - Due to saccadic eye movements the retinal image is abruptly displaced 2-4 times a second, yet we experience a stable and continuous stream of vision. It is known that saccades modulate neural processing in various local brain areas, but the question of how saccades influence neural communication between different areas in the thalamo-cortical system has remained unanswered. By combining transcranial magnetic stimulation with electroencephalography, we found that saccades were accompanied by dynamic changes in causal communication between different brain areas in humans. These changes were anticipatory; they began before the actual eye movement. Compared with fixation, communication between posterior cortical areas was first briefly enhanced during saccades, but subsequently peri-saccadic information did not ignite sustained activity in fronto-parietal cortices. This suggests that the brain constructs a spatially stable and temporally continuous stream of conscious vision from discrete fixations by restricting the access of peri-saccadic visual information to sustained processing in fronto-parietal cortices. PMID- 27365301 TI - Developing research, policy and practice in palliative care for people with intellectual disabilities will benefit everyone. PMID- 27365298 TI - Early Activation of Experience-Independent Dendritic Spine Turnover in a Mouse Model of Alzheimer's Disease. AB - Synaptic loss is critical in Alzheimer's disease (AD), but the dynamics of synapse turnover are poorly defined. We imaged dendritic spines in transgenic APPswe/PSen1?E9 (APP/PS1) cerebral cortex. Dendritic spine turnover is increased far from plaque in aged APP/PS1 mice, and in young APP/PS1 mice prior to plaque formation. Dysregulation occurs in the presence of soluble Abeta oligomer and requires cellular prion protein (PrPC). APP/PS1 mice lack responsiveness of spine turnover to sensory stimulation. Critically, enhanced spine turnover is coupled with the loss of persistent spines starting early and continuing with age. To evaluate mechanisms of experience-independent supranormal spine turnover, we analyzed the transcriptome of young APP/PS1 mouse brain when turnover is altered but synapse density and memory are normal, and plaque and inflammation are absent. Early PrPC-dependent expression changes occur in synaptic and lipid metabolizing genes. Thus, pathologic synaptic dysregulation underlying AD begins at a young age prior to Abeta plaque. PMID- 27365300 TI - Palmitoylation of cdc42 Promotes Spine Stabilization and Rescues Spine Density Deficit in a Mouse Model of 22q11.2 Deletion Syndrome. AB - 22q11.2 deletion syndrome (22q11DS) is associated with learning and cognitive dysfunctions and a high risk of developing schizophrenia. It has become increasingly clear that dendritic spine plasticity is tightly linked to cognition. Thus, understanding how genes involved in cognitive disorders affect synaptic networks is a major challenge of modern biology. Several studies have pointed to a spine density deficit in 22q11DS transgenic mice models. Using the LgDel mouse model, we first quantified spine deficit at different stages using electron microscopy. Next we performed repetitive confocal imaging over several days on hippocampal organotypic cultures of LgDel mice. We show no imbalanced ratio between daily spine formation and spine elimination, but a decreased spine life expectancy. We corrected this impaired spine stabilization process by overexpressing ZDHHC8 palmitoyltransferase, whose gene belongs to the LgDel microdeletion. Overexpression of one of its substrates, the cdc42 brain-specific variant, under a constitutively active form (cdc42-palm-CA) led to the same result. Finally, we could rescue spine density in vivo, in adult LgDel mice, by injecting pups with a vector expressing cdc42-palm-CA. This study reveals a new role of ZDHHC8-cdc42-palm molecular pathway in postsynaptic structural plasticity and provides new evidence in favor of the dysconnectivity hypothesis for schizophrenia. PMID- 27365302 TI - A Core Outcome Set for Children With Feeding Tubes and Neurologic Impairment: A Systematic Review. AB - CONTEXT: Uncertainty exists about the impacts of feeding tubes on neurologically impaired children. Core outcome sets (COS) standardize outcome selection, definition, measurement, and reporting. OBJECTIVE: To synthesize an evidence base of qualitative data on all outcomes selected and/or reported for neurologically impaired children 0 to 18 years living with gastrostomy/gastrojejunostomy tubes. DATA SOURCES: Medline, Embase, and Cochrane Register databases searched from inception to March 2014. STUDY SELECTION: Articles examining health outcomes of neurologically impaired children living with feeding tubes. DATA EXTRACTION: Outcomes were extracted and assigned to modified Outcome Measures in Rheumatology 2.0 Filter core areas; death, life impact, resource use, pathophysiological manifestations, growth and development. RESULTS: We identified 120 unique outcomes with substantial heterogeneity in definition, measurement, and frequency of selection and/or reporting: "pathophysiological manifestation" outcomes (n = 83) in 79% of articles; "growth and development" outcomes (n = 13) in 55% of articles; "death" outcomes (n = 3) and "life impact" outcomes (n = 17) in 39% and 37% of articles, respectively; "resource use" outcomes (n = 4) in 14%. Weight (50%), gastroesophageal reflux (35%), and site infection (25%) were the most frequently reported outcomes. LIMITATIONS: We were unable to investigate effect size of outcomes because quantitative data were not collected. CONCLUSIONS: The paucity of outcomes assessed for life impact, resource use and death hinders meaningful evidence synthesis. A COS could help overcome the current wide heterogeneity in selection and definition. These results will form the basis of a consensus process to produce a final COS. PMID- 27365303 TI - Iron-Refractory Iron Deficiency Anemia May Not Lead to Neurocognitive Dysfunction: A Case Report. AB - Iron deficiency is a common cause of anemia (IDA) in infancy and can be associated with neurocognitive impairments. Iron-refractory IDA (IRIDA) has recently been described as an inherited cause of IDA due to loss-of-function mutations in the TMPRSS6 gene. IRIDA is characterized by a lack of response to iron replacement. Here we report a new case of IRIDA with its biological parameters and its functional consequences, including neuropsychological impact. The latter was evaluated by the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition and subtests. We report a 5-year-old French Canadian boy who was incidentally diagnosed with a severe microcytic anemia at 2 years of age (hemoglobin 52 g/L, mean corpuscular volume 50 fL). Except mild pallor, he was asymptomatic of his anemia. Although he had a slight response to intravenous iron therapy, his hemoglobin remained <92 g/L, with persistent microcytosis, low serum iron, but normal ferritin levels. Blood hepcidin level was higher than those of his parents and control (patient 11.2 nM, father 9.06 nM, mother 4.07 nM). Compound heterozygosity for TMPRSS6 paternally inherited c.1324G>A and maternally inherited c.1807G>C mutations were eventually identified. The patient had normal development and growth. Neuropsychological evaluation revealed excellent performance, with high Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition scores (ie, 82nd percentile for both global intelligence and general ability index). In conclusion, TMPRSS6 c.1807G>C in conjunction with c.1324G>A results in IRIDA. In contrast to the usual form of IDA, IRIDA may not be associated with neuropsychological deficits. PMID- 27365304 TI - Author Response to McKean, Vande Voort, and Croarkin (2016). PMID- 27365305 TI - Lee et al. Trends in Metabolic Syndrome Severity and Lifestyle Factors Among Adolescents. Pediatrics. 2016;137(3);doi:10.1542/peds.2015-3177. PMID- 27365306 TI - Faundez et al. Diabetic Striatopathy in Childhood: A Case Report. Pediatrics. 2016;137(4);doi:10542/peds.2014-3761. PMID- 27365307 TI - Incidence and Outcome of CPAP Failure in Preterm Infants. AB - BACKGROUND AND OBJECTIVES: Data from clinical trials support the use of continuous positive airway pressure (CPAP) for initial respiratory management in preterm infants, but there is concern regarding the potential failure of CPAP support. We aimed to examine the incidence and explore the outcomes of CPAP failure in Australian and New Zealand Neonatal Network data from 2007 to 2013. METHODS: Data from inborn preterm infants managed on CPAP from the outset were analyzed in 2 gestational age ranges (25-28 and 29-32 completed weeks). Outcomes after CPAP failure (need for intubation <72 hours) were compared with those succeeding on CPAP using adjusted odds ratios (AORs). RESULTS: Within the cohort of 19 103 infants, 11 684 were initially managed on CPAP. Failure of CPAP occurred in 863 (43%) of 1989 infants commencing on CPAP at 25-28 weeks' gestation and 2061 (21%) of 9695 at 29-32 weeks. CPAP failure was associated with a substantially higher rate of pneumothorax, and a heightened risk of death, bronchopulmonary dysplasia (BPD) and other morbidities compared with those managed successfully on CPAP. The incidence of death or BPD was also increased: (25-28 weeks: 39% vs 20%, AOR 2.30, 99% confidence interval 1.71-3.10; 29-32 weeks: 12% vs 3.1%, AOR 3.62 [2.76-4.74]). The CPAP failure group had longer durations of respiratory support and hospitalization. CONCLUSIONS: CPAP failure in preterm infants is associated with increased risk of mortality and major morbidities, including BPD. Strategies to promote successful CPAP application should be pursued vigorously. PMID- 27365308 TI - Lack of Rating Scale Normalization and a Socioeconomically Advantaged Population Limits the Generalizability of Preadolescent Transgender Findings. PMID- 27365309 TI - Phosphatidylcholine passes through lateral tight junctions for paracellular transport to the apical side of the polarized intestinal tumor cell-line CaCo2. AB - Phosphatidylcholine (PC) is the most abundant phospholipid in intestinal mucus, indicative of a specific transport system across the mucosal epithelium to the intestinal lumen. To elucidate this transport mechanism, we employed a transwell tissue culture system with polarized CaCo2 cells. It was shown that PC could not substantially be internalized by the cells. However, after basal application of increasing PC concentrations, an apical transport of 47.1+/-6.3nmolh(-1)mMPC(-1) was observed. Equilibrium distribution studies with PC applied in equal concentrations to the basal and apical compartments showed a 1.5-fold accumulation on the expense of basal PC. Disruption of tight junctions (TJ) by acetaldehyde or PPARgamma inhibitors or by treatment with siRNA to TJ proteins suppressed paracellular transport by at least 50%. Transport was specific for the choline containing the phospholipids PC, lysoPC and sphingomyelin. We showed that translocation is driven by an electrochemical gradient generated by apical accumulation of Cl(-) and HCO3(-) through CFTR. Pretreatment with siRNA to mucin 3 which anchors in the apical plasma membrane of mucosal cells inhibited the final step of luminal PC secretion. PC accumulates in intestinal mucus using a paracellular, apically directed transport route across TJs. PMID- 27365310 TI - MEK1/2 inhibitors activate macrophage ABCG1 expression and reverse cholesterol transport-An anti-atherogenic function of ERK1/2 inhibition. AB - Expression of ATP-binding cassette transporter G1 (ABCG1), a molecule facilitating cholesterol efflux to HDL, is activated by liver X receptor (LXR). In this study, we investigated if inhibition of ERK1/2 can activate macrophage ABCG1 expression and functions. MEK1/2 inhibitors, PD98059 and U0126, increased ABCG1 mRNA and protein expression, and activated the natural ABCG1 promoter but not the promoter with the LXR responsive element (LXRE) deletion. Inhibition of ABCG1 expression by ABCG1 siRNA did enhance the formation of macrophage/foam cells and it attenuated the inhibitory effect of MEK1/2 inhibitors on foam cell formation. MEK1/2 inhibitors activated macrophage cholesterol efflux to HDL in vitro, and they enhanced reverse cholesterol transport (RCT) in vivo. ApoE deficient (apoE(-/-)) mice receiving U0126 treatment had reduced sinus lesions in the aortic root which was associated with activated macrophage ABCG1 expression in the lesion areas. MEK1/2 inhibitors coordinated the RXR agonist, but not the LXR agonist, to induce ABCG1 expression. Furthermore, induction of ABCG1 expression by MEK1/2 inhibitors was associated with activation of SIRT1, a positive regulator of LXR activity, and inactivation of SULT2B1 and RIP140, two negative regulators of LXR activity. Taken together, our study suggests that MEK1/2 inhibitors activate macrophage ABCG1 expression/RCT, and inhibit foam cell formation and lesion development by multiple mechanisms, supporting the concept that ERK1/2 inhibition is anti-atherogenic. PMID- 27365311 TI - Increased plasmid copy number is essential for Yersinia T3SS function and virulence. AB - Pathogenic bacteria have evolved numerous virulence mechanisms that are essential for establishing infections. The enterobacterium Yersinia uses a type III secretion system (T3SS) encoded by a 70-kilobase, low-copy, IncFII-class virulence plasmid. We report a novel virulence strategy in Y. pseudotuberculosis in which this pathogen up-regulates the plasmid copy number during infection. We found that an increased dose of plasmid-encoded genes is indispensable for virulence and substantially elevates the expression and function of the T3SS. Remarkably, we observed direct, tight coupling between plasmid replication and T3SS function. This regulatory pathway provides a framework for further exploration of the environmental sensing mechanisms of pathogenic bacteria. PMID- 27365312 TI - The communities of Science. PMID- 27365314 TI - Emergence of healing in the Antarctic ozone layer. AB - Industrial chlorofluorocarbons that cause ozone depletion have been phased out under the Montreal Protocol. A chemically driven increase in polar ozone (or "healing") is expected in response to this historic agreement. Observations and model calculations together indicate that healing of the Antarctic ozone layer has now begun to occur during the month of September. Fingerprints of September healing since 2000 include (i) increases in ozone column amounts, (ii) changes in the vertical profile of ozone concentration, and (iii) decreases in the areal extent of the ozone hole. Along with chemistry, dynamical and temperature changes have contributed to the healing but could represent feedbacks to chemistry. Volcanic eruptions have episodically interfered with healing, particularly during 2015, when a record October ozone hole occurred after the Calbuco eruption. PMID- 27365313 TI - Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. AB - Ideally, therapy for autoimmune diseases should eliminate pathogenic autoimmune cells while sparing protective immunity, but feasible strategies for such an approach have been elusive. Here, we show that in the antibody-mediated autoimmune disease pemphigus vulgaris (PV), autoantigen-based chimeric immunoreceptors can direct T cells to kill autoreactive B lymphocytes through the specificity of the B cell receptor (BCR). We engineered human T cells to express a chimeric autoantibody receptor (CAAR), consisting of the PV autoantigen, desmoglein (Dsg) 3, fused to CD137-CD3zeta signaling domains. Dsg3 CAAR-T cells exhibit specific cytotoxicity against cells expressing anti-Dsg3 BCRs in vitro and expand, persist, and specifically eliminate Dsg3-specific B cells in vivo. CAAR-T cells may provide an effective and universal strategy for specific targeting of autoreactive B cells in antibody-mediated autoimmune disease. PMID- 27365316 TI - Evaluation of multiple-channel OFDM based airborne ultrasonic communications. AB - Orthogonal frequency division multiplexing (OFDM) modulation has been extensively used in both wired and wireless communication systems. The use of OFDM technology allows very high spectral efficiency data transmission without using complex equalizers to correct the effect of a frequency-selective channel. This work investigated OFDM methods in an airborne ultrasonic communication system, using commercially available capacitive ultrasonic transducers operating at 50kHz to transmit information through the air. Conventional modulation schemes such as binary phase shift keying (BPSK) and quadrature amplitude modulation (QAM) were used to modulate sub-carrier signals, and the performances were evaluated in an indoor laboratory environment. Line-of-sight (LOS) transmission range up to 11m with no measurable errors was achieved using BPSK at a data rate of 45kb/s and a spectral efficiency of 1b/s/Hz. By implementing a higher order modulation scheme (16-QAM), the system data transfer rate was increased to 180kb/s with a spectral efficiency of 4b/s/Hz at attainable transmission distances up to 6m. Diffraction effects were incorporated into a model of the ultrasonic channel that also accounted for beam spread and attenuation in air. The simulations were a good match to the measured signals and non-LOS signals could be demodulated successfully. The effects of multipath interference were also studied in this work. By adding cyclic prefix (CP) to the OFDM symbols, the bit error rate (BER) performance was significantly improved in a multipath environment. PMID- 27365315 TI - North Atlantic ocean circulation and abrupt climate change during the last glaciation. AB - The most recent ice age was characterized by rapid and hemispherically asynchronous climate oscillations, whose origin remains unresolved. Variations in oceanic meridional heat transport may contribute to these repeated climate changes, which were most pronounced during marine isotope stage 3, the glacial interval 25 thousand to 60 thousand years ago. We examined climate and ocean circulation proxies throughout this interval at high resolution in a deep North Atlantic sediment core, combining the kinematic tracer protactinium/thorium (Pa/Th) with the deep water-mass tracer, epibenthic delta(13)C. These indicators suggest reduced Atlantic overturning circulation during every cool northern stadial, with the greatest reductions during episodic Hudson Strait iceberg discharges, while sharp northern warming followed reinvigorated overturning. These results provide direct evidence for the ocean's persistent, central role in abrupt glacial climate change. PMID- 27365317 TI - Quasi-ordered C60 molecular films grown on the pseudo-ten-fold (1 0 0) surface of the Al13Co4 quasicrystalline approximant. AB - The growth of C60 films on the pseudo-ten-fold (1 0 0) surface of the orthorhombic Al13Co4 quasicrystalline approximant was studied experimentally by scanning tunneling microscopy, low-energy electron diffraction and photoemission spectroscopy. The (1 0 0) surface terminates at bulk-planes presenting local atomic configurations with five-fold symmetry-similar to quasicrystalline surfaces. While the films deposited at room temperature were found disordered, high-temperature growth (up to 693 K) led to quasi-ordered molecular films templated on the substrate rectangular unit mesh. The most probable adsorption sites and geometries were investigated by density functional theory (DFT) calculations. A large range of adsorption energies was determined, influenced by both symmetry and size matching at the molecule-substrate interface. The quasi ordered structure of the film can be explained by C60 adsorption at the strongest adsorption sites which are too far apart compared to the distance minimizing the intermolecular interactions, resulting in some disorder in the film structure at a local scale. Valence band photoemission indicates a broadening of the molecular orbitals resulting from hybridization between the substrate and overlayer electronic states. Dosing the film at temperature above 693 K led to molecular damage and formation of carbide thin films possessing no azimuthal order with respect to the substrate. PMID- 27365318 TI - Efficacy of an Internet-based, individually tailored smoking cessation program: A randomized-controlled trial. AB - Introduction Self-help computer-based programs are easily accessible and cost effective interventions with a great recruitment potential. However, each program is different and results of meta-analyses may not apply to each new program; therefore, evaluations of new programs are warranted. The aim of this study was to assess the marginal efficacy of a computer-based, individually tailored program (the Coach) over and above the use of a comprehensive Internet smoking cessation website. Methods A two-group randomized controlled trial was conducted. The control group only accessed the website, whereas the intervention group received the Coach in addition. Follow-up was conducted by e-mail after three and six months (self-administrated questionnaires). Of 1120 participants, 579 (51.7%) responded after three months and 436 (38.9%) after six months. The primary outcome was self-reported smoking abstinence over four weeks. Results Counting dropouts as smokers, there were no statistically significant differences between intervention and control groups in smoking cessation rates after three months (20.2% vs. 17.5%, p = 0.25, odds ratio (OR) = 1.20) and six months (17% vs. 15.5%, p = 0.52, OR = 1.12). Excluding dropouts from the analysis, there were statistically significant differences after three months (42% vs. 31.6%, p = 0.01, OR = 1.57), but not after six months (46.1% vs. 37.8%, p = 0.081, OR = 1.41). The program also significantly increased motivation to quit after three months and self-efficacy after three and six months. Discussion An individually tailored program delivered via the Internet and by e-mail in addition to a smoking cessation website did not significantly increase smoking cessation rates, but it increased motivation to quit and self-efficacy. PMID- 27365319 TI - Perceptions of telepractice pedagogy in speech-language pathology: A quantitative analysis. AB - Introduction Despite the growth of telecommunication applications to provide clinical healthcare services, there has been little attention to the pedagogical framework needed to train healthcare students to deliver these services. Methods In this exploratory investigation, perceptions of speech-language pathology/therapy (SLP/SLT) faculty ( n = 31), graduate students ( n = 16), and telehealth ("telepractice") clinicians ( n = 16) were examined with a 15-item survey regarding the 1) comparative pedagogical importance of four skills common to telepractice and face-to-face service (f2f) delivery, and 2) relative pedagogical value of seven skills and competencies unique to telepractice. Results Statistical analyses revealed nonverbal communication skills and knowledge of the literature related to service delivery methods were more important in telepractice than in f2f service delivery. Among seven skills unique to telepractice, participants believed the most important was solving problems related to the Internet and recommended at least two hours of instruction each in telepractice technology, patient confidentiality, and role-playing telepractice. Results suggest that SLP/SLT students may need additional and/or focused academic training in nonverbal communication, telepractice literature, and in solving connectivity issues to enter the telepractice marketplace with sufficient preparation. Discussion Further study is needed to compare the relative importance of additional SLP/SLT skills and competencies, describe components of effective healthcare training telepractice programs, and explore effective pedagogical strategies for healthcare telepractice instruction. PMID- 27365320 TI - Usability and feasibility of a mobile health system to provide comprehensive antenatal care in low-income countries: PANDA mHealth pilot study in Madagascar. AB - Background Madagascar's maternal health mortality ratio in 2013 was 478 deaths per 100,000 live births. Most deaths are related to direct complications during pregnancy and childbirth and could be reduced by providing comprehensive antenatal care (ANC). Objective The objective of the study was to assess the usability and feasibility of a mobile health system (mHealth) to provide high quality ANC, according to World Health Organization (WHO) recommendations. Methods PANDA (Pregnancy And Newborn Diagnostic Assessment) is an easy-to-use mHealth system that uses affordable communications technology to support diagnosis and health care worker decision-making regarding ANC. From January to March 2015, a cross-sectional pilot study was conducted in Ambanja District, Madagascar, in which ANC using PANDA was provided to 100 pregnant women. The collected data were transmitted to a database in the referral hospital to create individual electronic patient records. Accuracy and completeness of the data were closely controlled. The PANDA software was assessed and the number of abnormal results, treatments performed, and participants requiring referral to health care facilities were monitored. Results The PANDA system facilitated creation of individual electronic patient records that included socio-demographic and medical data for 100 participants. Duration of ANC visits averaged 29.6 min. Health care providers were able to collect all variables (100%) describing personal and medical data. No major technical problems were encountered and no data were lost. During 17 ANC visits (17%), an alert function was generated to highlight abnormal clinical results requiring therapy or referral to an affiliated hospital. Participants' acceptability of the system was very high. Conclusion This pilot study proved the usability and feasibility of the PANDA mHealth system to conduct complete and standardised ANC visits according to WHO guidelines, thus providing a promising solution to increase access to high-quality and standardised ANC for pregnant women in remote areas. PMID- 27365321 TI - Telemedicine coverage for post-operative ICU patients. AB - Introduction There is an increased demand for intensive care unit (ICU) beds. We sought to determine if we could create a safe surge capacity model to increase ICU capacity by treating ICU patients in the post-anaesthesia care unit (PACU) utilizing a collaborative model between an ICU service and a telemedicine service during peak ICU bed demand. Methods We evaluated patients managed by the surgical critical care service in the surgical intensive care unit (SICU) compared to patients managed in the virtual intensive care unit (VICU) located within the PACU. A retrospective review of all patients seen by the surgical critical care service from January 1st 2008 to July 31st 2011 was conducted at an urban, academic, tertiary centre and level 1 trauma centre. Results Compared to the SICU group ( n = 6652), patients in the VICU group ( n = 1037) were slightly older (median age 60 (IQR 47-69) versus 58 (IQR 44-70) years, p = 0.002) and had lower acute physiology and chronic health evaluation (APACHE) II scores (median 10 (IQR 7-14) versus 15 (IQR 11-21), p < 0.001). The average amount of time patients spent in the VICU was 13.7 + /-9.6 hours. In the VICU group, 750 (72%) of patients were able to be transferred directly to the floor; 287 (28%) required subsequent admission to the surgical intensive care unit. All patients in the VICU group were alive upon transfer out of the PACU while mortality in the surgical intensive unit cohort was 5.5%. Discussion A collaborative care model between a surgical critical care service and a telemedicine ICU service may safely provide surge capacity during peak periods of ICU bed demand. The specific patient populations for which this approach is most appropriate merits further investigation. PMID- 27365322 TI - Three-Territory DWI Acute Infarcts: Diagnostic Value in Cancer-Associated Hypercoagulation Stroke (Trousseau Syndrome). AB - BACKGROUND AND PURPOSE: DWI infarcts involving the bilateral anterior and posterior circulation suggest an embolic etiology. In the absence of an identifiable embolic source, we analyzed DWI lesions involving these 3 cerebral territories to determine the diagnostic value for ischemic infarction caused by cancer-associated hypercoagulation. MATERIALS AND METHODS: A retrospective analysis of all brain MR imaging studies at our institution from July 2014 to June 2015 was conducted, yielding 4075 studies. Of those, 17% (n = 709) contained the terms "restricted-diffusion" plus either "numerous," "innumerable," "multiple," or "bilateral." Of these 709 reports, 6% (n = 41) of DWI lesions involving 3 or more vascular territories of the bilateral anterior and posterior circulation were analyzed. RESULTS: Of the 41 patients, 19 separate etiologies were identified, the most frequent being malignancy-related infarctions (22% [n = 9]) and hypoxic-ischemic injury (12% [n = 5]). Only 2 patients had an indeterminate etiology. The most frequent etiology of infarctions not suspected clinically or radiographically was malignancy (P < .001). Infarctions of malignancy had a characteristic appearance, being nonenhancing, nonring-appearing clusters or single areas of restricted diffusion of 0.5-2 cm with a peripheral location or larger vascular territories, uncommonly in a watershed distribution, and with absence of diffuse cortical ribbon or deep gray nuclei involvement. CONCLUSIONS: Approximately 1 in 5 ischemic infarcts in patients with DWI lesions involving 3 vessel territories are malignancy related. In the absence of an identifiable embolic source, ischemic infarction with cancer-associated hypercoagulation accounts for 75% of cases. Cancer-associated hypercoagulation infarction should be considered, particularly when no other cause is apparent. PMID- 27365323 TI - Orbital Fat Volumetry and Water Fraction Measurements Using T2-Weighted FSE-IDEAL Imaging in Patients with Thyroid-Associated Orbitopathy. AB - BACKGROUND AND PURPOSE: The quantitative evaluation of orbital fat proliferation and edema and the assessment of extraocular muscles are useful for diagnosing and monitoring thyroid-associated orbitopathy. To evaluate therapy-induced quantitative changes in the orbital fat of patients with thyroid-associated orbitopathy, we performed volumetric and water fraction measurements by using T2 weighted FSE iterative decomposition of water and fat with echo asymmetry and least-squares estimation (FSE-IDEAL) imaging. MATERIALS AND METHODS: Orbital FSE IDEAL images of 30 volunteers were acquired twice within 1 week. Nine patients with thyroid-associated orbitopathy underwent FSE-IDEAL imaging before and after methylprednisolone pulse therapy, and the treatment results were assessed by using their pre- and post-methylprednisolone pulse therapy clinical activity scores. We performed volumetric and water fraction measurements of orbital fat by using FSE-IDEAL imaging and evaluated interscan differences in the volunteers. In patients with thyroid-associated orbitopathy, we compared pre- and posttherapy orbital fat measurements and assessed the correlation between the pretherapy values and clinical activity score improvement. RESULTS: The reproducibility of results obtained by the quantitative evaluation of orbital fat in volunteers was acceptable. After methylprednisolone pulse therapy, the water fraction in the orbital fat of patients with thyroid-associated orbitopathy was significantly decreased (P < .001). There was a significant positive correlation between the pretherapy water fraction and clinical activity score improvement (right, r = 0.82; left, r = 0.79) and a significant negative correlation between the pretherapy volume and clinical activity score improvement (bilateral, r = -0.84). CONCLUSIONS: Volumetric and water fraction measurements of orbital fat by using FSE-IDEAL imaging are feasible and useful for monitoring the effects of therapy and for predicting the response of patients with thyroid-associated orbitopathy to methylprednisolone pulse therapy. PMID- 27365324 TI - Mechanical Thrombectomy in Patients with Acute Ischemic Stroke and Lower NIHSS Scores: Recanalization Rates, Periprocedural Complications, and Clinical Outcome. AB - BACKGROUND AND PURPOSE: Mechanical thrombectomy, in addition to intravenous thrombolysis, has become standard in acute ischemic stroke treatment in patients with large-vessel occlusion in the anterior circulation. However, previous randomized controlled stroke trials were not focused on patients with mild-to moderate symptoms. Thus, there are limited data for patient selection, prediction of clinical outcome, and occurrence of complications in this patient population. The purpose of this analysis was to assess clinical and interventional data in patients treated with mechanical thrombectomy in case of ischemic stroke with mild-to-moderate symptoms. MATERIALS AND METHODS: We performed a retrospective analysis of a prospectively collected stroke data base. Inclusion criteria were anterior circulation ischemic stroke treated with mechanical thrombectomy at our institution between September 2010 and October 2015 with an NIHSS score of <=8. RESULTS: Of 484 patients, we identified 33 (6.8%) with the following characteristics: median NIHSS = 5 (interquartile range, 4-7), median onset-to groin puncture time = 320 minutes (interquartile range, 237-528 minutes). Recanalization (TICI = 2b-3) was achieved in 26 (78.7%) patients. Two cases of symptomatic intracranial hemorrhage were observed. Favorable (mRS 0-2) and moderate (mRS 0-3) clinical outcome at 90 days was achieved in 21 (63.6%) and 30 (90.9%) patients, respectively. CONCLUSIONS: The clinical outcome of patients undergoing mechanical thrombectomy for acute ischemic stroke with mild stroke due to large-vessel occlusion appears to be predominately favorable, even in a prolonged time window. However, although infrequent, angiographic complications could impair clinical outcome. Future randomized controlled trials should assess the benefit compared with the best medical treatment. PMID- 27365325 TI - Virtual-versus-Real Implantation of Flow Diverters: Clinical Potential and Influence of Vascular Geometry. AB - BACKGROUND AND PURPOSE: Intracranial stents have become extremely important in the endovascular management of complex intracranial aneurysms. Sizing and landing zone predictions are still very challenging steps in the procedure. Virtual stent deployment may help therapeutic planning, device choice, and hemodynamic simulations. We aimed to assess the predictability of our recently developed virtual deployment model by comparing in vivo and virtual stents implanted in a consecutive series of patients presenting with intracranial aneurysms. MATERIALS AND METHODS: Virtual stents were implanted in patient-specific geometries of intracranial aneurysms treated with the Pipeline Embolization Device. The length and cross-section of virtual and real stents measured with conebeam CT were compared. The influence of vessel geometry modifications occurring during the intervention was analyzed. RESULTS: The virtual deployment based on pre- and poststent implantation 3D rotational angiography overestimated (underestimated) the device length by 13% +/- 11% (-9% +/- 5%). These differences were highly correlated (R2 = 0.67) with the virtual-versus-real stent radius differences of 6% +/- 7% (5% +/- 4%) for predictions based on pre- and poststent implantation 3D rotational angiography. These mismatches were due principally to implantation concerns and vessel-shape modifications. CONCLUSIONS: The recently proposed geometric model was shown to predict accurately the deployment of Pipeline Embolization Devices when the stent radius was well-assessed. However, unpredictable delivery manipulations and variations of vessel geometry occurring during the intervention might impact the stent implantation. PMID- 27365326 TI - High-Resolution MRI Findings following Trigeminal Rhizotomy. AB - BACKGROUND AND PURPOSE: Patients with trigeminal neuralgia often undergo trigeminal rhizotomy via radiofrequency thermocoagulation or glycerol injection for treatment of symptoms. To date, radiologic changes in patients with trigeminal neuralgia post-rhizotomy have not been described, to our knowledge. The aim of this study was to evaluate patients after trigeminal rhizotomy to characterize post-rhizotomy changes on 3D high-resolution MR imaging. MATERIALS AND METHODS: A retrospective review of trigeminal neuralgia protocol studies was performed in 26 patients after rhizotomy compared with 54 treatment-naive subjects with trigeminal neuralgia. Examinations were reviewed independently by 2 neuroradiologists blinded to the side of symptoms and treatment history. The symmetry of Meckel's cave on constructive interference in steady-state and the presence of contrast enhancement within the trigeminal nerves on volumetric interpolated breath-hold examination images were assessed subjectively. The signal intensity of Meckel's cave was measured on coronal noncontrast constructive interference in steady-state imaging on each side. RESULTS: Post rhizotomy changes included subjective clumping of nerve roots and/or decreased constructive interference in steady-state signal intensity within Meckel's cave, which was identified in 17/26 (65%) patients after rhizotomy and 3/54 (6%) treatment-naive patients (P < .001). Constructive interference in steady-state signal intensity within Meckel's cave was, on average, 13% lower on the side of the rhizotomy in patients posttreatment compared with a 1% difference in controls (P < .001). Small regions of temporal encephalomalacia were noted in 8/26 (31%) patients after rhizotomy and 0/54 (0%) treatment-naive patients (P < .001). CONCLUSIONS: Post-trigeminal rhizotomy findings frequently include nerve clumping and decreased constructive interference in steady-state signal intensity in Meckel's cave. Small areas of temporal lobe encephalomalacia are encountered less frequently. PMID- 27365327 TI - Reply. PMID- 27365328 TI - The Clinical Outcome of Posterior Reversible Encephalopathy Syndrome. PMID- 27365329 TI - High-Convexity Tightness Predicts the Shunt Response in Idiopathic Normal Pressure Hydrocephalus. AB - BACKGROUND AND PURPOSE: Although neuroimaging plays an important role in the diagnosis of idiopathic normal pressure hydrocephalus, its predictive value for response to shunt surgery has not been established. The purpose of the current study was to identify neuroimaging markers that predict the shunt response of idiopathic normal pressure hydrocephalus. MATERIALS AND METHODS: Sixty patients with idiopathic normal pressure hydrocephalus underwent presurgical brain MR imaging and clinical evaluation before and 1 year after shunt surgery. The assessed MR imaging features included the Evans index, high-convexity tightness, Sylvian fissure dilation, callosal angle, focal enlargement of the cortical sulci, bumps in the lateral ventricular roof, and deep white matter and periventricular hyperintensities. The idiopathic normal pressure hydrocephalus grading scale total score was used as a primary clinical outcome measure. We used measures for individual symptoms (ie, the idiopathic normal pressure hydrocephalus grading scale subdomain scores, such as gait, cognitive, and urinary scores), the Timed Up and Go test, and the Mini-Mental State Examination as secondary clinical outcome measures. The relationships between presurgical neuroimaging features and postoperative clinical changes were investigated by using simple linear regression analysis. To identify the set of presurgical MR imaging features that best predict surgical outcomes, we performed multiple linear regression analysis by using a bidirectional stepwise method. RESULTS: Simple linear regression analyses demonstrated that presurgical high-convexity tightness, callosal angle, and Sylvian fissure dilation were significantly associated with the 1-year changes in the clinical symptoms. A multiple linear regression analysis demonstrated that presurgical high-convexity tightness alone predicted the improvement of the clinical symptoms 1 year after surgery. CONCLUSIONS: High-convexity tightness is a neuroimaging feature predictive of shunt response in idiopathic normal pressure hydrocephalus. PMID- 27365330 TI - Cervical Spinal Cord DTI Is Improved by Reduced FOV with Specific Balance between the Number of Diffusion Gradient Directions and Averages. AB - BACKGROUND AND PURPOSE: Reduced-FOV DTI is promising for exploring the cervical spinal cord, but the optimal set of parameters needs to be clarified. We hypothesized that the number of excitations should be favored over the number of diffusion gradient directions regarding the strong orientation of the cord in a single rostrocaudal axis. MATERIALS AND METHODS: Fifteen healthy individuals underwent cervical spinal cord MR imaging at 3T, including an anatomic 3D-Multi Echo Recombined Gradient Echo, high-resolution full-FOV DTI with a NEX of 3 and 20 diffusion gradient directions and 5 sets of reduced-FOV DTIs differently balanced in terms of NEX/number of diffusion gradient directions: (NEX/number of diffusion gradient directions = 3/20, 5/16, 7/12, 9/9, and 12/6). Each DTI sequence lasted 4 minutes 30 seconds, an acceptable duration, to cover C1-C4 in the axial plane. Fractional anisotropy maps and tractograms were reconstructed. Qualitatively, 2 radiologists rated the DTI sets blinded to the sequence. Quantitatively, we compared distortions, SNR, variance of fractional anisotropy values, and numbers of detected fibers. RESULTS: Qualitatively, reduced-FOV DTI sequences with a NEX of >=5 were significantly better rated than the full-FOV DTI and the reduced-FOV DTI with low NEX (N = 3) and a high number of diffusion gradient directions (D = 20). Quantitatively, the best trade-off was reached by the reduced-FOV DTI with a NEX of 9 and 9 diffusion gradient directions, which provided significantly fewer artifacts, higher SNR on trace at b = 750 s/mm2 and an increased number of fibers tracked while maintaining similar fractional anisotropy values and dispersion. CONCLUSIONS: Optimized reduced-FOV DTI improves spinal cord imaging. The best compromise was obtained with a NEX of 9 and 9 diffusion gradient directions, which emphasizes the need for increasing the NEX at the expense of the number of diffusion gradient directions for spinal cord DTI contrary to brain DTI. PMID- 27365331 TI - Magnetic Susceptibility from Quantitative Susceptibility Mapping Can Differentiate New Enhancing from Nonenhancing Multiple Sclerosis Lesions without Gadolinium Injection. AB - BACKGROUND AND PURPOSE: Magnetic susceptibility values of multiple sclerosis lesions increase as they change from gadolinium-enhancing to nonenhancing. Can susceptibility values measured on quantitative susceptibility mapping without gadolinium injection be used to identify the status of lesion enhancement in surveillance MR imaging used to monitor patients with MS? MATERIALS AND METHODS: In patients who had prior MR imaging and quantitative susceptibility mapping in a current MR imaging, new T2-weighted lesions were evaluated for enhancement on conventional T1-weighted imaging with gadolinium, and their susceptibility values were measured on quantitative susceptibility mapping. Receiver operating characteristic analysis was used to assess the diagnostic accuracy of using quantitative susceptibility mapping in distinguishing new gadolinium-enhancing from new nonenhancing lesions. A generalized estimating equation was used to assess differences in susceptibility values among lesion types. RESULTS: In 54 patients, we identified 86 of 133 new lesions that were gadolinium-enhancing and had relative susceptibility values significantly lower than those of nonenhancing lesions (beta = -17.2; 95% CI, -20.2 to -14.2; P < .0001). Using susceptibility values to discriminate enhancing from nonenhancing lesions, we performed receiver operating characteristic analysis and found that the area under the curve was 0.95 (95% CI, 0.92-0.99). Sensitivity was measured at 88.4%, and specificity, at 91.5%, with a cutoff value of 11.2 parts per billion for quantitative susceptibility mapping-measured susceptibility. CONCLUSIONS: During routine MR imaging monitoring to detect new MS lesion activity, quantitative susceptibility mapping can be used without gadolinium injection for accurate identification of the BBB leakage status in new T2WI lesions. PMID- 27365332 TI - Disrupted Brain Connectivity Patterns in Patients with Type 2 Diabetes. AB - BACKGROUND AND PURPOSE: Type 2 diabetes is associated with an increased risk of dementia. This study investigated the global connectivity patterns in the brains of patients with type 2 diabetes by using a functional MR imaging technique. MATERIALS AND METHODS: Forty patients and 43 age-, sex-, and education-matched healthy controls underwent resting-state functional imaging in a 3T MR imaging unit. Degree centrality, a commonly used measurement of global connectivity, was computed for a full-brain exploration of the regions influenced by type 2 diabetes. We then examined the functional connectivity of each region by using the seed-based approach. Finally, voxelwise correlation analyses were performed to explore the relationship among the connectivity changes, cognitive performance, and diabetes-related variables. RESULTS: Patients exhibited decreased degree centrality in the left lingual gyrus and increased centrality in the right insula and dorsal anterior cingulate cortex (corrected P < .05). The occipital network anchored in the lingual gyrus showed extensively reduced connectivity, while the network connectivity of the insula and cingulate cortex (mostly included in the salience network) was significantly elevated (corrected P < .05). Correlational analyses revealed that in the diabetic group, impaired visual memory and executive function performance were correlated with occipital hypoconnectivity, while higher fasting plasma glucose levels and better executive functioning were related to anterior cingulate cortex hyperconnectivity (all corrected P values < .05). Similar effects were not detected in the controls. CONCLUSIONS: This preliminary study shows that network connectivity is altered in patients with type 2 diabetes, which may provide critical insight into the neural substrate of diabetes-related cognitive decline. PMID- 27365333 TI - A comparison of mechanical properties between different percentage layups of a single-style carbon fibre ankle foot orthosis. AB - BACKGROUND: Currently, a range of 'off-the-shelf' ankle foot orthoses are used in clinical practice, of various functions and designs. Their use relates to immediate control over mild conditions. OBJECTIVES: To investigate the properties of carbon fibre ankle foot orthoses at different percentage layups and provide a comparison of these through assessment of the (1) elastic properties, (2) deflection about the ankle (including the calculation of stiffness) and (3) failure under compressive forces (dorsiflexion). STUDY DESIGN: Experimental, bench test. METHODS: Literature was reviewed to derive a suitable bench test for mechanical testing of ankle foot orthoses. Two universal Instron machines were used to apply the necessary forces. A pilot device was utilised to establish the range of forces appropriate to confirm the setup chosen was effective. Each test was then carried out on nine ankle foot orthoses (3 * 3 different percentage layups). RESULTS: All nine devices had their elastic properties deduced. Stiffness exhibited greater resistance in tension, with angular deflection being greatest in the 'Lite' set and least in the Rigid. Failure occurred mainly due to fracture, proximally on the strut; however, this was not consistent among the devices. CONCLUSION: Results confirmed the properties expected of carbon fibre ankle foot orthoses were consistent. This can now be related to functionality and therefore specific device prescription options. Clinical relevance This article attempts to increase the understanding and develop the area of mechanically testing ankle foot orthoses. This was achieved by comparing carbon fibre at different percentage layups on an identical design and their resultant structural properties. This article outlines a clear and simple setup for obtaining repeatable results. PMID- 27365334 TI - Urethane anesthesia in acute lower urinary tract studies in the male rat. AB - Urethane is a widely used anesthetic in animal lower urinary tract research. Our objective was to investigate the quality of anesthesia and the correlation between bladder (voiding) contractions, micturition pressure, bladder capacity and urethane dosage and body weight. Urethane was given subcutaneously and/or intraperitoneally (1.0-1.2 g/kg). The bladder was filled with saline and the bladder pressure was recorded continuously. Animals in which the subcutaneous/intraperitoneal ratio was higher needed less urethane. Heavier animals needed less extra urethane. In animals, in which no bladder contractions could be evoked, the total amount of urethane given was similar to that in those that did show contractions. In the animals that did void, the bladder never emptied completely and residual volumes remained. There was no relationship between animal weight or total amount of urethane and mean capacity. Anesthesia lasted up till 14 h, during which bladder (voiding) contractions could be recorded. Considering all results, we conclude that urethane is a well suited anesthetic for acute lower urinary tract physiological research in the intact rat. PMID- 27365335 TI - Effects of Liver Transplantation on Lipids and Cardiovascular Disease in Children With Homozygous Familial Hypercholesterolemia. AB - Homozygous familial hypercholesterolemia (HoFH) is a rare, inherited, life threatening, metabolic disorder of low-density lipoprotein (LDL) receptor function characterized by elevated serum LDL cholesterol (LDL-C) and rapidly progressive atherosclerotic cardiovascular disease (ACVD). Since LDL receptors are predominantly found on hepatocytes, orthotopic liver transplantation (OLT) has emerged as a viable intervention for HoFH because LDL receptor activity is restored. This study assessed the effects of OLT on ACVD and ACVD risk factors in pediatric patients with HoFH. We analyzed lipids, lipoproteins, body mass index, glucose, blood pressure, and cardiovascular imaging in 8 pediatric patients who underwent OLT for HoFH. Total serum cholesterol, LDL-C, lipoprotein (a), and apolipoprotein B/apolipoprotein A1 ratio decreased to normal values in all subjects (p values <0.001) at 1 month after OLT and were maintained for the length of follow-up (2 to 6 years). There were few complications related to surgery or immunosuppressive therapy. Two patients developed mild hypertension. In the first 4 subjects monitored for 4 to 6 years after OLT, coronary artery disease did not develop or progress except in 1 minor artery in 1 subject and actually regressed in 2 subjects with >50% stenosis. However, aortic valve stenosis progressed in 2 of 4 subjects. In conclusion, OLT is an effective therapeutic option for patients with HoFH with coronary artery disease and persistently elevated serum LDL-C despite maximum medical therapy. Aortic valvular disease may progress. Long-term data are needed to evaluate the true risk-benefit ratio of this surgical approach. PMID- 27365336 TI - Crossover between cooperative and fractal relaxation in complex glass-formers. AB - Kinetics of physical aging at different temperatures is studied in situ in arsenic selenide glasses using high-precision differential scanning calorimetry technique. A well-expressed step-like behaviour in the enthalpy recovery kinetics is recorded for low aging temperatures. These fine features disappear when the aging temperature (T a) approaches the glass transition temperature (T g). The overall kinetics is described by stretched exponential function with stretching exponent close to 3/5 at T a > ~0.95 T g almost independent on glass composition, and 3/7 when the aging temperature drops to ~0.9 T g. These values are consistent with the prediction of Phillips' diffusion-to-traps model. Further decrease in aging temperature to ~0.85 T g leads to the appearance of step-like behaviour and stretching exponent of 1/3 for the overall kinetics, which is the limiting value predicted by random walk on the fractal model. Such behavior is explained as crossover from homogeneous cooperative relaxation of non-percolating structural units to high-dimensional fractal relaxation within hierarchically arranged two-stage physical aging model. PMID- 27365337 TI - Distribution and trafficking of the MU-opioid receptor in enteric neurons of the guinea pig. AB - The MU-opioid receptor (MOR) is a major regulator of gastrointestinal motility and secretion and mediates opiate-induced bowel dysfunction. Although MOR is of physiological and therapeutic importance to gut function, the cellular and subcellular distribution and regulation of MOR within the enteric nervous system are largely undefined. Herein, we defined the neurochemical coding of MOR expressing neurons in the guinea pig gut and examined the effects of opioids on MOR trafficking and regulation. MOR expression was restricted to subsets of enteric neurons. In the stomach MOR was mainly localized to nitrergic neurons (~88%), with some overlap with neuropeptide Y (NPY) and no expression by cholinergic neurons. These neurons are likely to have inhibitory motor and secretomotor functions. MOR was restricted to noncholinergic secretomotor neurons (VIP-positive) of the ileum and distal colon submucosal plexus. MOR was mainly detected in nitrergic neurons of the colon (nitric oxide synthase positive, 87%), with some overlap with choline acetyltransferase (ChAT). No expression of MOR by intrinsic sensory neurons was detected. [d-Ala(2), MePhe(4), Gly(ol)(5)]enkephalin (DAMGO), morphiceptin, and loperamide induced MOR endocytosis in myenteric neurons. After stimulation with DAMGO and morphiceptin, MOR recycled, whereas MOR was retained within endosomes following loperamide treatment. Herkinorin or the delta-opioid receptor agonist [d-Ala(2), d Leu(5)]enkephalin (DADLE) did not evoke MOR endocytosis. In summary, we have identified the neurochemical coding of MOR-positive enteric neurons and have demonstrated differential trafficking of MOR in these neurons in response to established and putative MOR agonists. PMID- 27365338 TI - GGsTop, a novel and specific gamma-glutamyl transpeptidase inhibitor, protects hepatic ischemia-reperfusion injury in rats. AB - Ischemia-reperfusion (IR) injury is a major clinical problem and is associated with numerous adverse effects. GGsTop [2-amino-4{[3 (carboxymethyl)phenyl](methyl)phosphono}butanoic acid] is a highly specific and irreversible gamma-glutamyl transpeptidase (gamma-GT) inhibitor. We studied the protective effects of GGsTop on IR-induced hepatic injury in rats. Ischemia was induced by clamping the portal vein and hepatic artery of left lateral and median lobes of the liver. Before clamping, saline (IR group) or saline containing 1 mg/kg body wt of GGsTop (IR-GGsTop group) was injected into the liver through the inferior vena cava. At 90 min of ischemia, blood flow was restored. Blood was collected before induction of ischemia and prior to restoration of blood flow and at 12, 24, and 48 h after reperfusion. All the animals were euthanized at 48 h after reperfusion and the livers were harvested. Serum levels of alanine transaminase, aspartate transaminase, and gamma-GT were significantly lower after reperfusion in the IR-GGsTop group compared with the IR group. Massive hepatic necrosis was present in the IR group, while only few necroses were present in the IR-GGsTop group. Treatment with GGsTop increased hepatic GSH content, which was significantly reduced in the IR group. Furthermore, GGsTop prevented increase of hepatic gamma-GT, malondialdehyde, 4-hydroxynonenal, and TNF-alpha while all these molecules significantly increased in the IR group. In conclusion, treatment with GGsTop increased glutathione levels and prevented formation of free radicals in the hepatic tissue that led to decreased IR-induced liver injury. GGsTop could be used as a pharmacological agent to prevent IR-induced liver injury and the related adverse events. PMID- 27365339 TI - Human Resources for Health Challenges in Nigeria and Nurse Migration. AB - The emigration of sub-Saharan African health professionals to developed Western nations is an aspect of increasing global mobility. This article focuses on the human resources for health challenges in Nigeria and the emigration of nurses from Nigeria as the country faces mounting human resources for health challenges. Human resources for health issues in Nigeria contribute to poor population health in the country, alongside threats from terrorism, infectious disease outbreaks, and political corruption. Health inequities within Nigeria mirror the geographical disparities in human resources for health distribution and are worsened by the emigration of Nigerian nurses to developed countries such as the United States and the United Kingdom. Nigerian nurses are motivated to emigrate to work in healthier work environments, improve their economic prospects, and advance their careers. Like other migrant African nurses, they experience barriers to integration, including racism and discrimination, in receiving countries. We explore the factors and processes that shape this migration. Given the forces of globalization, source countries and destination countries must implement policies to more responsibly manage migration of nurses. This can be done by implementing measures to retain nurses, promote the return migration of expatriate nurses, and ensure the integration of migrant nurses upon arrival in destination countries. PMID- 27365340 TI - Draft Genome Sequence of Pseudomonas sp. Strain BMS12, a Plant Growth-Promoting and Protease-Producing Bacterium, Isolated from the Rhizosphere Sediment of Phragmites karka of Chilika Lake, India. AB - We report the 4.51 Mb draft genome of Pseudomonas sp. strain BMS12, a Gram negative bacterium in the class of Gammaproteobacteria, isolated from the rhizospheric sediment of Phragmites karka, an invasive weed in Chilika Lake, Odisha, India. The Pseudomonas sp. strain BMS12 is capable of producing proteases and is also an efficient plant growth promoter that can be useful for various phytoremedial and industrial applications. PMID- 27365342 TI - Whole-Genome Shotgun Sequencing and Annotation of Mycobacterium tuberculosis MTB221/11 Isolated from a Cerebrospinal Fluid Sample in Malaysia. AB - Here, we report of the annotated genome sequence of Mycobacterium tuberculosis MTB221/11. The organism was isolated from the cerebrospinal fluid of a patient in Malaysia. PMID- 27365341 TI - Draft Genome Sequence of Halobacillus sp. Strain KGW1, a Moderately Halophilic and Alkaline Protease-Producing Bacterium Isolated from the Rhizospheric Region of Phragmites karka from Chilika Lake, Odisha, India. AB - Halobacillus sp. strain KGW1 is a moderately halophilic, rod shaped, Gram positive, yellow pigmented, alkaline protease-producing bacterium isolated from a water sample from Chilika Lake, Odisha, India. Sequencing of bacterial DNA assembled a 3.68-Mb draft genome. The genome annotation analysis showed various gene clusters for tolerance to stress, such as elevated pH, salt concentration, and toxic metals. PMID- 27365343 TI - Draft Genome Sequence of Acinetobacter sp. Strain BMW17, a Cellulolytic and Plant Growth-Promoting Bacterium Isolated from the Rhizospheric Region of Phragmites karka of Chilika Lake, India. AB - We report the 3.16 Mb draft genome of Acinetobacter sp. strain BMW17, a Gram negative bacterium in the class of Gammaproteobacteria, isolated from the rhizospheric region of Phragmites karka, an invasive weed in Chilika Lake, Odisha, India. The strain BMW17(T) is capable of degrading cellulose and is also an efficient plant growth promoter that can be useful for various phytoremedial and commercial applications. PMID- 27365344 TI - Use of Multiple Sequencing Technologies To Produce a High-Quality Genome of the Fungus Pseudogymnoascus destructans, the Causative Agent of Bat White-Nose Syndrome. AB - White-nose syndrome has recently emerged as one of the most devastating wildlife diseases recorded, causing widespread mortality in numerous bat species throughout eastern North America. Here, we present an improved reference genome of the fungal pathogen Pseudogymnoascus destructans for use in comparative genomic studies. PMID- 27365345 TI - Draft Genome Sequence of a New Zealand Rickettsia-Like Organism Isolated from Farmed Chinook Salmon. AB - We report here the draft genome sequence of a rickettsia-like organism, isolated from a New Zealand Chinook salmon farm experiencing high mortality. The genome is approximately 3 Mb in size, has a G+C content of approximately 39.2%, and is predicted to contain 2,870 coding sequences. PMID- 27365346 TI - Genome Sequence of Gordonia Bacteriophage Lucky10. AB - Lucky10 is a newly isolated phage of Gordonia terrae 3612 that was recovered from a soil sample in Pittsburgh, PA. Lucky10 has siphoviral morphology and a double stranded DNA (dsDNA) genome of 42,979 bp, with 70 predicted protein-coding genes. Lucky10 shows little similarity to previously reported Gordonia phages. PMID- 27365347 TI - Genome Sequences of Gordonia terrae Phages Attis and SoilAssassin. AB - Attis and SoilAssassin are two closely related bacteriophages isolated on Gordonia terrae 3612 from separate soil samples in Pittsburgh, PA. The Attis and SoilAssassin genomes are 47,881 bp and 47,880 bp, respectively, and have 74 predicted protein-coding genes, including toxin-antitoxin systems, but no tRNAs. PMID- 27365349 TI - Draft Genome Sequence of 16SrIII-J Phytoplasma, a Plant Pathogenic Bacterium with a Broad Spectrum of Hosts. AB - Phytoplasmas are bacterial plant pathogens that can affect different vegetal hosts. In South America, a phytoplasma belonging to ribosomal subgroup 16SrIII-J has been reported in many crops. Here we report its genomic draft sequence, showing a total length of 687,253 bp and a G+C content of 27.72%. PMID- 27365348 TI - Genome Sequences of Gordonia Bacteriophages Obliviate, UmaThurman, and Guacamole. AB - We describe three newly isolated phages-Obliviate, UmaThurman, and Guacamole-that infect Gordonia terrae 3612. The three genomes are related to one another but are not closely related to other previously sequenced phages or prophages. The three phages are predicted to use integration-dependent immunity systems as described in several mycobacteriophages. PMID- 27365350 TI - Complete Genome Sequence of Aurantimicrobium minutum Type Strain KNCT, a Planktonic Ultramicrobacterium Isolated from River Water. AB - Aurantimicrobium minutum type strain KNC(T) is a planktonic ultramicrobacterium isolated from river water in western Japan. Strain KNC(T) has an extremely small, streamlined genome of 1,622,386 bp comprising 1,575 protein-coding sequences. The genome annotation suggests that strain KNC(T) has an actinorhodopsin-based photometabolism. PMID- 27365351 TI - Draft Genome Sequences of Gluconobacter cerinus CECT 9110 and Gluconobacter japonicus CECT 8443, Acetic Acid Bacteria Isolated from Grape Must. AB - We report here the draft genome sequences of Gluconobacter cerinus strain CECT9110 and Gluconobacter japonicus CECT8443, acetic acid bacteria isolated from grape must. Gluconobacter species are well known for their ability to oxidize sugar alcohols into the corresponding acids. Our objective was to select strains to oxidize effectively d-glucose. PMID- 27365352 TI - High-Quality Draft Genome Sequences for Five Non-O157 Shiga Toxin-Producing Escherichia coli Strains Generated with PacBio Sequencing and Optical Maps. AB - Shiga toxin-producing Escherichia coli (STEC) is a foodborne pathogen. We report here the high-quality draft whole-genome sequences of five STEC strains isolated from clinical cases in the United States. This report is for STEC of serotypes O55:H7, O79:H7, O91:H14, O153:H2, and O156:H25. PMID- 27365353 TI - Genome Sequence of the Red Pigment-Forming Meiothermus taiwanensis Strain RP Isolated from Paniphala Hot Spring, India. AB - Here we report the draft genome sequence of Meiothermus taiwanensis strain RP (MCC 2966), isolated from the Paniphala hot spring of India, which contains genes encoding for enzymes of the methyl erythritol 4-phosphate (MEP) pathway of isoprenoid biosynthesis and carotenoid backbone synthesis. PMID- 27365354 TI - Genome Sequence of Bradyrhizobium stylosanthis Strain BR 446T, a Nitrogen-Fixing Symbiont of the Legume Pasture Stylosanthes guianensis. AB - Bradyrhizobium stylosanthis BR 446(T) is a nitrogen-fixing symbiont of the tropical legume pasture Stylosanthes guianensis Its draft genome contains 8,801,717 bp and 8,239 coding sequences (CDSs). Several putative genes that might confer high competitiveness and saprophytic capacity under the stressful conditions of tropical soils were identified in the genome. PMID- 27365355 TI - Complete Genome Sequences of Four Isolates of Plutella xylostella Granulovirus. AB - Granuloviruses are widespread pathogens of Plutella xylostella L. (diamondback moth) and potential biopesticides for control of this global insect pest. We report the complete genomes of four Plutella xylostella granulovirus isolates from China, Malaysia, and Taiwan exhibiting pairs of noncoding, homologous repeat regions with significant sequence variation but equivalent length. PMID- 27365356 TI - First Draft Genome Sequence of a Mycobacterium gordonae Clinical Isolate. AB - Here, we report the first draft genome sequence of the clinically relevant species Mycobacterium gordonae The clinical isolate Mycobacterium gordonae 14 8773 was obtained from the sputum of a patient with mycobacteriosis. PMID- 27365357 TI - Complete Genome Sequence of Wohlfahrtiimonas chitiniclastica Strain BM-Y, Isolated from the Pancreas of a Zebra in China. AB - Here, a complete genome sequence of Wohlfahrtiimonas chitiniclastica strain BM-Y is presented. The whole genome is 2.18-Mb and contains a blaVEB-1 gene cassette which endows it with resistance to ceftazidime, ampicillin, tetracycline, etc. To our knowledge, this is the first time that an extended spectrum beta-lactamase (ESBL) type W. chitiniclastica strain has been found. PMID- 27365358 TI - Genome Sequence of the Psychrophilic Bacterium Tenacibaculum ovolyticum Strain da5A-8 Isolated from Deep Seawater. AB - Some bacterial species of the genus Tenacibaculum, including Tenacibaculum ovolyticum, have been known as fish pathogens in the sea. So far, the only published genome sequence for this genus is for Tenacibaculum dicentrarchi, which could also be a fish pathogen. Strain da5A-8, showing 100% identity to the 16S rRNA gene sequence of T. ovolyticum DSM 18103(T), was isolated from seawater at a depth of 344 m in Kochi, Japan, and grew optimally at 10 to 20 degrees C. The genome sequence of strain da5A-8 revealed the possible virulence genes commonly observed in the genus Tenacibaculum. PMID- 27365359 TI - Complete Genome Sequence of Campylobacter iguaniorum Strain RM11343, Isolated from an Alpaca. AB - Campylobacter iguaniorum is a member of the C. fetus group of campylobacters and is one of two Campylobacter taxa isolated from reptiles. This study describes the whole-genome sequence of the C. iguaniorum strain RM11343, which was isolated from a California alpaca fecal sample. PMID- 27365360 TI - Genome Sequence of the Historical Clinical Isolate Burkholderia pseudomallei PHLS 6. AB - Here, we present the draft genome sequence of Burkholderia pseudomallei PHLS 6, a virulent clinical strain isolated from a melioidosis patient in Bangladesh in 1960. The draft genome consists of 39 contigs and is 7,322,181 bp long. PMID- 27365361 TI - Charge transport in thin layer Na x CoO2 (x ~ 0.63) studied by terahertz spectroscopy. AB - Charge transport in Na0.63CoO2 thin film deposited by a spin-coating method was investigated experimentally by time-domain terahertz spectroscopy and theoretically using Monte Carlo calculations of charge response in nano structured materials. The dominating type of transport mechanism over the entire investigated range of temperatures (20-300 K) is a metallic-like conductivity of charges partly confined in constituting nano-sized grains. Due to the granular character of our thin film, the scattering time at low temperatures is limited by scattering on grain boundaries and the conductivity is strongly suppressed due to capture of a major fraction of charge carriers in deep traps. Nevertheless, our experimental setup and the applied model allowed us to distinguish the parameters related to the grain interior from those influenced by grain boundaries, and to conclude that the metallic type of conductivity is the intrinsic property relevant to single crystal materials. PMID- 27365362 TI - Thermoelectric signals of state transition in polycrystalline SmB6. AB - Topological Kondo insulator SmB6 has attracted quite a lot of attention from the condensed matter physics community. A number of unique electronic properties, including low-temperature resistivity anomaly, 1D electronic transport and 2D Fermi surfaces have been observed in SmB6. Here, we report on thermoelectric transport properties of polycrystalline SmB6 over a broad temperature from 300 to 2 K. An anomalous transition in the temperature-dependent Seebeck coefficient S from S(T) [Formula: see text] T (-1) to S(T) [Formula: see text] T was observed around 12 K. Such a transition demonstrates a transition of conductivity from 3D metallic bulk states to 2D metallic surface states with insulating bulk states. Our results suggest that the thermotransport measurements could be used for the characterization of state transition in topological insulators. PMID- 27365363 TI - Detectable Risks in Studies of the Fetal Benefits of Maternal Influenza Vaccination. AB - Maternal influenza vaccination prevents influenza illness in both mothers and newborns. Results from some recent studies have suggested that influenza vaccination might also prevent adverse pregnancy outcomes, such as preterm birth. However, it is challenging to conduct epidemiologic studies to evaluate the benefits to the fetus of maternal influenza vaccination because the causal benefit of vaccination is likely only experienced by the small fraction of the cohort in whom influenza illness is prevented by vaccination. The plausibility of detecting true differences in risks between groups under such conditions is rarely discussed. We aimed to inform the interpretation of studies in which the fetal benefits of maternal influenza vaccination are evaluated by estimating detectable risk ratios and necessary sample sizes for different study scenarios. Estimates of rates of influenza illness, vaccine effectiveness, vaccine uptake, and preterm birth and of the association of influenza illness with preterm birth were identified from the published literature. We calculated detectable risk ratios for preterm birth in vaccinated versus unvaccinated women and the associated sample size requirements. Our results demonstrated that under most scenarios, plausible differences between groups will be extremely challenging to detect (risk ratios for preterm birth of 0.9 to 1.0) and will require sample sizes infeasible for prospective epidemiologic research. This suggests that the large fetal benefits from influenza vaccination observed in epidemiologic studies are unlikely to be causal. PMID- 27365364 TI - Public engagement in Malawi through a health-talk radio programme ' Umoyo nkukambirana': A mixed-methods evaluation. AB - Radio is an effective source of health information in many resource poor countries. In Malawi, 53% of households own radios however few radio programmes in Malawi focus on health issues in the context of medical research. An interactive health-talk radio programme ' Umoyo nkukambirana' was introduced by Malawi-Liverpool-Wellcome Trust Clinical Research Programme on a national radio station. The aim was to increase awareness of health and medical research, and improve engagement between researchers, healthcare workers and the public. The content and presentation were developed through participatory community consultations. Focus Group Discussions were conducted with established Radio Listening Clubs whilst quantitative data was collected using toll free FrontlineSMS to explore national response. A total of 277 to 695 SMS (Median: 477) were received per theme. The majority of SMS were received from men (64%) and mainly from rural areas (54%). The programme improved knowledge of medical research, health and dispelled misconceptions. This study suggests that the radio may be an effective means of increasing the exposure of men to health information in resource poor settings. PMID- 27365366 TI - Three-dimensional chiral skyrmions with attractive interparticle interactions. AB - We introduce a new class of isolated three-dimensional skyrmion that can occur within the cone phase of chiral magnetic materials. These novel solitonic states consist of an axisymmetric core separated from the host phase by an asymmetric shell. These skyrmions attract one another. We derive regular solutions for isolated skyrmions arising in the cone phase of cubic helimagnets and investigate their bound states. PMID- 27365365 TI - Diverse alternative back-splicing and alternative splicing landscape of circular RNAs. AB - Circular RNAs (circRNAs) derived from back-spliced exons have been widely identified as being co-expressed with their linear counterparts. A single gene locus can produce multiple circRNAs through alternative back-splice site selection and/or alternative splice site selection; however, a detailed map of alternative back-splicing/splicing in circRNAs is lacking. Here, with the upgraded CIRCexplorer2 pipeline, we systematically annotated different types of alternative back-splicing and alternative splicing events in circRNAs from various cell lines. Compared with their linear cognate RNAs, circRNAs exhibited distinct patterns of alternative back-splicing and alternative splicing. Alternative back-splice site selection was correlated with the competition of putative RNA pairs across introns that bracket alternative back-splice sites. In addition, all four basic types of alternative splicing that have been identified in the (linear) mRNA process were found within circRNAs, and many exons were predominantly spliced in circRNAs. Unexpectedly, thousands of previously unannotated exons were detected in circRNAs from the examined cell lines. Although these novel exons had similar splice site strength, they were much less conserved than known exons in sequences. Finally, both alternative back-splicing and circRNA-predominant alternative splicing were highly diverse among the examined cell lines. All of the identified alternative back-splicing and alternative splicing in circRNAs are available in the CIRCpedia database (http://www.picb.ac.cn/rnomics/circpedia). Collectively, the annotation of alternative back-splicing and alternative splicing in circRNAs provides a valuable resource for depicting the complexity of circRNA biogenesis and for studying the potential functions of circRNAs in different cells. PMID- 27365367 TI - The Role of Relaxin in Normal and Abnormal Uterine Function During the Menstrual Cycle and Early Pregnancy. AB - The hormone relaxin is a 6-kDa peptide with high structural similarity to insulin. It is primarily produced by the corpus luteum during pregnancy but is also synthesized by other reproductive organs such as the uterus, decidua, and placenta. Relaxin binds to its receptor RXFP1, which has been localized to a wide variety of reproductive and nonreproductive tissues. The peptide's many uterotropic effects include stimulating uterine growth and vascularization, remodeling extracellular matrix components, and regulating vascular endothelial growth factor in preparation for implantation. Evidence also supports a role for relaxin in the systemic maternal vascular adaptations required for a healthy pregnancy. Diminished relaxin levels in early pregnancy are linked with increased risks of miscarriage and the development of preeclampsia. In addition to pregnancy, relaxin may also play a functional role in the uterus during the menstrual cycle, and modified relaxin activity may contribute to gynecological disorders such as uterine fibrosis and endometriosis. Despite over 75 years of research, we still have a limited understanding of relaxin's broad roles in the uterus, particularly as there are significant species differences in its synthesis and activity, which restricts the use of animal models for human centric questions. Here, we review current knowledge regarding relaxin actions in the human uterus during the menstrual cycle and in early pregnancy, with a focus on its potential roles in various gynecological disorders, as well as the pregnancy disorders such as preeclampsia, recurrent miscarriage, and early pregnancy loss. PMID- 27365368 TI - Association of Polymorphisms in Connective Tissue Growth Factor and Epidermal Growth Factor Receptor Genes With Human Longevity. AB - Growth pathways play key roles in longevity. The present study tested single nucleotide polymorphisms (SNPs) in the connective tissue growth factor gene (CTGF) and the epidermal growth factor receptor gene (EGFR) for association with longevity. Comparison of allele and genotype frequencies of 12 CTGF SNPs and 41 EGFR SNPs between 440 American men of Japanese ancestry aged >=95 years and 374 men of average life span revealed association with longevity at the p < .05 level for 2 SNPs in CTGF and 7 in EGFR. Two in CTGF and two in EGFR remained significant after Bonferroni correction. The SNPs of both CTGF and EGFR were in a haplotype block in each respective gene. Haplotype analysis confirmed the suggestive association found by chi2 analysis. We noted an excess of heterozygotes among the longevity cases, consistent with heterozygote advantage in living to extreme old age. No associations of the most significant SNPs were observed in whites or Koreans. In conclusion, the present findings indicate that genetic variation in CTGF and EGFR may contribute to the attainment of extreme old age in Japanese. More research is needed to confirm that genetic variation in CTGF and EGFR contributes to the attainment of extreme old age across human populations. PMID- 27365369 TI - Treatment pathways in an inception lupus cohort over the first three years. AB - Objective The treatment algorithm for new onset systemic lupus erythematosus (SLE) is less well defined than for other rheumatic diseases. We examined the treatment patterns in an inception cohort of SLE patients over the first three years of disease between 2000 and 2010. Methods Patients fulfilled the American College of Rheumatology classification criteria for SLE within 12 months of enrollment and completed three subsequent annual visits. Data collection included patient demographics, SLE manifestations, medications, SLE disease activity index 2K (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index. Analysis included descriptive statistics and repeated measures mixed models. Results Seventy-nine patients, 83.5% female and 91.1% Caucasian were studied. At baseline the mean (SD) age was 40.6 (16.4) years, disease duration was 0.36 (0.28) years and SLEDAI-2K was 5.7 (4.6). Over three years, cumulative use of corticosteroids, antimalarials and immunosuppressants was 53.2%, 77.2% and 40.5% respectively. Corticosteroids were usually used in combination with antimalarials and/or immunosuppressants. Between baseline and final assessments the use of corticosteroids fell (44.3% vs 15.2%) in contrast to antimalarials (55.7% vs 70.9%) and immunosuppressants (26.6% vs 34.2%). Of 44/79 (55.7%) patients not receiving corticosteroids at baseline 84.1% remained off corticosteroids for the study duration. Thirty-seven of 79 (46.8%) patients never received corticosteroids and only 5/79 (6.3%) at all four assessments. Patients taking corticosteroids at baseline had higher mean (SD) daily dose and cumulative dose over three years compared with patients not on corticosteroids at baseline (9.0 (0.8) vs 0.3 (1.3) mg; 10.8 (8.5) vs 0.3 (1.2) g). As a group, SLE patients who used corticosteroids either at baseline, at any time in the three year study or in high cumulative doses had the highest average disease activity scores over the same time frame and had a significant fall in SLEDAI-2K scores ( p < 0.05) compared with patients not exposed to corticosteroids. Conclusion Use of corticosteroids occurred in approximately half of new onset SLE, usually in combination with antimalarials and/or immunosuppressants. It was associated with both higher disease activity at baseline and improvement over time. Patients who did not receive corticosteroids at presentation were unlikely to do so over the next three years. PMID- 27365371 TI - Adipokines, tumor necrosis factor and its receptors in female patients with systemic lupus erythematosus. AB - OBJECTIVES: To analyze the association of adipokines and tumor necrosis factor alpha (TNFalpha) and its receptors with characteristics of systemic lupus erythematosus (SLE) and to investigate the correlation between adipokines and the TNF system. METHODS: One hundred and thirty-six SLE women, aged >=18 years old, were assessed. TNFalpha, soluble TNFalpha receptors 1 (sTNFR1) and 2 (sTNFR2) and adipokines were analyzed by ELISA kits. RESULTS: The median (IQR) of age was 41.5 (33.0-49.7) years old and of disease duration 11.3 (7.8-15.8) years. The median (IQR) of disease activity was 0 (0-4) and of damage index was 2 (1-3). Higher levels of sTNFR1 and sTNFR2 were associated with nephritis (p < 0.001 for both), and sTNFR1 (p = 0.025) and TNFalpha (p = 0.014) were positively associated with arthritis. Higher sTNFR1 levels were found in participants that were not using antimalarial drugs (p = 0.04). Independent correlation was found between sTNFR1 (beta = 0.253; p = 0.003) and sTNFR2 (beta = 0.297; p < 0.001) levels and disease activity and damage index (sTNFR1: beta = 0.367; p < 0.001; sTNFR2: beta = 0.335; p < 0.001). Higher adiponectin levels were independently associated with nephritis (p = 0.009) and antimalarial drugs use (p = 0.015). There was a positive correlation between leptin and sTNFR2 levels (p = 0.002) and between resistin levels and sTNFR1 (p < 0.001) and sTNFR2 (p < 0.001). CONCLUSION: The correlation between adipokines and TNF system allows a better understanding of the role of adipokines in the inflammatory response in SLE patients. PMID- 27365370 TI - Incidence of systemic lupus erythematosus in a population-based cohort using revised 1997 American College of Rheumatology and the 2012 Systemic Lupus International Collaborating Clinics classification criteria. AB - In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) group published a new set of classification criteria for systemic lupus erythematosus (SLE). Studies applying these criteria to real-life scenarios have found either equal or greater sensitivity and equal or lower specificity to the 1997 ACR classification criteria (ACR 97). Nonetheless, there are no studies that have used the SLICC 12 criteria to investigate the incidence of lupus. We used the resource of the Rochester Epidemiology Project to identify incident SLE patients in Olmsted County, Minnesota, from 1993 to 2005, who fulfilled the ACR 97 or SLICC 12 criteria. A total of 58 patients met criteria by SLICC 12 and 44 patients met criteria by ACR 97. The adjusted incidence of 4.9 per 100,000 person years by SLICC 12 was higher than that by ACR 97 (3.7 per 100,000 person-years, p = 0.04). The median duration from the appearance of first criterion to fulfillment of the criteria was shorter for the SLICC 12 than for ACR 97 (3.9 months vs 8.1 months). The higher incidence by SLICC 12 criteria came primarily from the ability to classify patients with renal-limited disease, the expansion of the immunologic criteria and the expansion of neurologic criteria. PMID- 27365372 TI - Chronic myelomonocytic leukemia mimicking hematologic systemic lupus erythematosus. AB - The relationship between primary hematologic disease and rheumatologic manifestations is well known, especially acute lymphocytic leukemia, lymphomas, plasma cell dyscrasias and myelodysplastic syndrome (MDS). Currently, more has been described about autoimmune manifestations in chronic myelomonocytic leukemia (CMML). Many different clinical scenarios may lead a patient with MDS/CMML initially to seek a rheumatological unit. Autoimmune features such as polymyalgia rheumatic symptoms, myositis, neutrophilic dermatosis, cutaneous vasculitis and positive antinuclear antibodies (ANA) are some examples of clinical presentation of MDS/CMML. Moreover, peripheral cytopenias are a common initial presentation both for systemic lupus erythematous (SLE) and MDS/CMML. The aim of this study was to describe a case of an elderly woman with thrombocytopenia and positivity of antibodies to anti-extractable nuclear antigens (anti-ENA) as initial manifestation of CMML mimicking SLE, and to present some clues that encourage the clinician to perform a bone marrow study in such a clinical scenario. PMID- 27365373 TI - Outcomes of Anatomic Anterior Cruciate Ligament Reconstruction: Bone-Quadriceps Tendon Graft Versus Double-Bundle Hamstring Tendon Graft. AB - BACKGROUND: The choice of graft type is an important factor to the outcome of anterior cruciate ligament (ACL) reconstruction. PURPOSE: To compare knee joint stability and functional outcomes of anatomic ACL reconstruction with double bundle hamstring tendon (DBHT) and bone-quadriceps tendon (BQT) autografts. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Ninety-six patients underwent ACL reconstruction with either DBHT (hamstring group) or BQT autograft (quadriceps group). Each group included 48 patients who were retrospectively matched on the basis of age, sex, and body mass index; there were no statistically significant differences between the 2 groups (all P > .05). All patients had a minimum follow-up of 2 years. Outcome evaluations included the manual laxity test, International Knee Documentation Committee subjective evaluation, Tegner activity score, modified Lysholm score, anterior knee pain questionnaire, KT-2000 arthrometer side-to-side difference, Cybex II isokinetic testing, and tunnel position evaluation by quadrant method. RESULTS: Manual laxity test results were significantly improved in both groups after surgery (all P < .05). The maximum KT-2000 arthrometer side-to-side difference improved from 4.0 to 1.9 mm in the hamstring group and 3.9 to 2.1 mm in the quadriceps group (P = .65). Modified Lysholm scores in the hamstring and quadriceps groups improved from 69.4 and 70.2 to 88.4 and 92.1 (P = .30), and International Knee Documentation Committee subjective evaluation scores improved from 56.0 and 60.3 to 77.9 and 80.2 (P = .37), respectively. Tegner activity scores for the hamstring and quadriceps groups were 4.7 and 4.6 preoperatively and 4.6 and 4.7 (P = .80) at final follow-up, respectively. There were no between-group differences on postoperative anterior knee pain (P > .05 for all questionnaire categories), nor were there differences in recovered extensor muscle strength during isokinetic testing (82.9% vs 81.0% at 60 deg/s, P = .71; 85.1% vs 83.8% at 180 deg/s, P = .81). However, flexor muscle strength recovery was better in the quadriceps group (86.6% vs 92.2% at 60 deg/s, P = .22; 87.1% vs 99.6% at 180 deg/s, P = .01). There were no significant differences in tunnel positioning between the 2 groups (all P > .05). CONCLUSION: Anatomic ACL reconstruction with the BQT autograft showed similar knee stability and functional outcome scores when compared with the DBHT autograft. Additionally, better flexor muscle strength recovery was found in the quadriceps group, indicating a potential advantage of the BQT autograft in ACL reconstruction. PMID- 27365374 TI - Surgical Treatment of Chronic Exertional Compartment Syndrome in Pediatric Patients. AB - BACKGROUND: Chronic exertional compartment syndrome (CECS) is a cause of leg pain in running athletes and is treated with fasciotomy after failure of nonoperative management. CECS is being seen with increased frequency in younger patients. The demographics and outcomes of fasciotomy for CECS in pediatric patients, including risk factors for treatment failure, have not been described. PURPOSE: To describe characteristics of pediatric patients with CECS and determine surgical outcomes of the condition in this population. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective review was performed for patients 18 years and younger treated surgically for CECS with compartment release at a single institution from 1995 to 2014. Demographic and condition characteristics, operative procedure, postoperative course, and clinical outcomes were recorded for 286 legs of 155 patients. Compartment pressure testing using the Pedowitz criteria confirmed the diagnosis in all patients. RESULTS: A total of 155 patients were included in the study (average patient age at presentation, 16.4 +/ 1.38 years); 136 (88%) were female. All 155 patients presented with leg pain; of these patients, 8 (5%) also had neurologic symptoms, and 131 (85%) presented with bilateral symptoms requiring bilateral compartment release. Symptoms were chronic in nature, with duration over 1 year in 63% of patients. The primary sport was most commonly reported as running (25%), soccer (23%), or field hockey (12%); 50% of patients were multisport athletes. Of 286 legs, 138 (48%) had only anterior and/or lateral compartments released, while 84 (29.4%) had all 4 compartments released. Documented return to sport was seen in 79.5% of patients. Outcomes analysis was performed for 250 of 286 legs. Of these 250 legs, 47 (18.8%) had recurrent CECS requiring reoperation at a median of 1.3 years (interquartile range, 0.8-3.5) after initial compartment release. For each additional month between presentation and release, the odds of recurrence decreased by 12% (P = .04). Legs with only anterior and/or lateral compartment released had 3.4 times (95% CI, 1.29-9.14) the odds of reoperation compared with legs that had all 4 compartments released (P = .01). Twenty-eight of 250 legs (11.2%) had wound issues that resolved with nonoperative management. No wounds required repeat surgical management. CONCLUSION: CECS in pediatric patients most commonly occurs in adolescent females participating in running sports. Fasciotomy results in a 79.5% return-to-sports rate. Recurrence occurs in 18.8% of patients, more commonly in patients undergoing anterior and lateral release only. PMID- 27365375 TI - Dissection of the Process of Brain Metastasis Reveals Targets and Mechanisms for Molecular-based Intervention. AB - Brain metastases outnumber the incidence of brain tumors by a factor of ten. Patients with brain metastases have a dismal prognosis and current treatment modalities achieve only a modest clinical benefit. We discuss the process of brain metastasis with respect to mechanisms and involved targets to outline options for therapeutic intervention and focus on breast and lung cancer, as well as melanoma. We describe the process of penetration of the blood-brain-barrier (BBB) by disseminated tumor cells, establishment of a metastatic niche, colonization and outgrowth in the brain parenchyma. Furthermore, the role of angiogenesis in colonization of the brain parenchyma, interactions of extravasated tumor cells with microglia and astrocytes, as well as their propensity for neuromimicry, is discussed. We outline targets suitable for prevention of metastasis and summarize targets suitable for treatment of established brain metastases. Finally, we highlight the implications of findings revealing druggable mutations in brain metastases that cannot be identified in matching primary tumors. PMID- 27365376 TI - Overexpression of HPV16 E6* Alters beta-Integrin and Mitochondrial Dysfunction Pathways in Cervical Cancer Cells. AB - BACKGROUND: High-risk human papillomaviruses (HPV) cause nearly all cases of cervical cancer, as well as many types of oral and anogenital cancer. Alternative splicing increases the capacity of the HPV genome to encode the proteins necessary for successful completion of its infectious life cycle. However, the roles of these splice variants, including E6*, the smaller splice isoform of the E6 oncogene, in carcinogenesis are not clear. MATERIALS AND METHODS: SiHa (HPV16(+)) and C33A (HPV(-)) cells were transfected with the E6* plasmid, and tandem mass tag-labeled protein levels were quantified by mass spectrometry. Proteomic analyses identified pathways affected by E6* in both HPV(+) and HPV(-) cells, and pathways were validated using in vitro methods. RESULTS: A total of 4,300 proteins were identified and quantified in lysates of SiHa and C33A cells with and without HPV16 E6* expression. SiHa and C33A cells expressing E6* underwent changes in protein expression affecting integrin signaling and mitochondrial dysfunction pathways, respectively. Subsequent experiments were performed to validate selected E6*-mediated alterations in protein levels. CONCLUSION: E6* modifies the expression of proteins involved in mitochondrial dysfunction and oxidative phosphorylation in C33A cells, and beta-integrin signaling in SiHa cells. PMID- 27365377 TI - Gene-expression Profiling in Patients with Plasma Cell Myeloma Treated with Novel Agents. AB - BACKGROUND/AIM: Novel agents such as thalidomide, lenalidomide and bortezomib have in part anti-angiogenic properties. In this study, we examined gene expression of angiogenic molecules in patients with plasma cell myeloma (PCM). MATERIALS AND METHODS: We included 93 patients with PCM treated with novel agents (immunomodulatory drugs (IMiDs), bortezomib or a combination of both). The mRNA levels of angiogenic molecules were measured using the Human Angiogenesis RT2 Profiler PCR Array. The response evaluation was performed after three cycles. RESULTS: Regarding all 93 patients, gene expression of 15 out of 84 genes tested (pre- and post-treatment and changes in levels pre-treatment/post-treatment) were significantly different in responders compared to non-responders. Responders had a lower expression of pro-angiogenic factors and increased expression of antiangiogenic factors. CONCLUSION: In the IMiD-treated groups we found significant changes of expression of angiogenic genes in responders compared to non-responders, whereas in the bortezomib-based group the difference in expression of angiogenic genes was not significant. PMID- 27365378 TI - Expression of microRNAs of C19MC in Different Histological Types of Testicular Germ Cell Tumour. AB - BACKGROUND: Testicular germ cell tumours (TGCTs) are the most common tumours in men aged from 20 to 40 years, with a steadily increasing incidence. This study aimed to characterize the expression of the miRNA cluster C19MC in TGCT and to evaluate the suitability of a C19MC miRNA as a serum biomarker. MATERIALS AND METHODS: By quantitative reverse transcription PCR, we measured the expression of miR-517a-3p, miR-519a-3p, and miR-519c 3p in tissue samples of 25 TGCTs and the level of miR-517a-3p in serum samples obtained pre- and postoperatively from the same patients. RESULTS: We detected a significantly higher expression of C19MC miRNAs in non-seminomas than in seminomas and in clinical stages 2 and 3 than in stage 1 in both tissue and serum samples. CONCLUSION: miRNAs of C19MC are overexpressed in more aggressive types of TGCT, suggesting they contribute to malignancy. Furthermore, they might serve as serum biomarkers for these types of TGCT. PMID- 27365379 TI - Epigenetic Modifications with DZNep, NaBu and SAHA in Luminal and Mesenchymal like Breast Cancer Subtype Cells. AB - BACKGROUND/AIM: Numerous studies have shown that breast cancer and epigenetic mechanisms have a very powerful interactive relation. The MCF7 cell line, representative of luminal subtype and the MDA-MB 231 cell line representative of mesenchymal-like subtype were treated respectively with a Histone Methyl Transferase Inhibitors (HMTi), 3-Deazaneplanocin hydrochloride (DZNep), two histone deacetylase inhibitors (HDACi), sodium butyrate (NaBu), and suberoylanilide hydroxamic acid (SAHA) for 48 h. MATERIALS AND METHODS: Chromatin immunoprecipitation (ChIP) was used to observe HDACis (SAHA and NaBu) and HMTi (DZNep) impact on histones and more specifically on H3K27me3, H3K9ac and H3K4ac marks with Q-PCR analysis of BRCA1, SRC3 and P300 genes. Furthermore, the HDACi and HMTi effects on mRNA and protein expression of BRCA1, SRC3 and P300 genes were checked. In addition, statistical analyses were used. RESULTS: In the MCF7 luminal subtype with positive ER, H3k4ac was significantly increased on BRCA1 with SAHA. On the contrary, in the MDA-MB 231 breast cancer cell line, representative of mesenchymal-like subtype with negative estrogen receptor, HDACis had no effect. Also, DZNEP decreased significantly H3K27me3 on BRCA1 in MDA-MB 231. Besides, on SRC3, a significant increase for H3K4ac was obtained in MCF7 treated with SAHA. And DZNEP had no effect in MCF7. Also, in MDA-MB 231 treated with DZNEP, H3K27me3 significantly decreased on SRC3 while H3K4ac was significantly increased in MDA-MB-231 treated with SAHA or NaBu for P300. CONCLUSION: Luminal and mesenchymal-like breast cancer subtype cell lines seemed to act differently to HDACis (SAHA and NaBu) or HMTi (DZNEP) treatments. PMID- 27365380 TI - Stimulation of the Estrogen Axis Induces Epithelial-Mesenchymal Transition in Human Salivary Cancer cells. AB - BACKGROUND: Salivary gland cancer is a common type of head and neck cancer characterized by occasional deep invasion and lung metastasis. The precise role of sex steroid hormones in salivary gland cancer is unclear. To address this issue, we investigated whether the estrogen axis modulates salivary adenocarcinoma (SAC) and whether hormone therapy can be an effective treatment. MATERIALS AND METHODS: The estrogen receptor (ER) was overexpressed in HSG human SAC cells that lack endogenous ER and the cells were treated with and without 17beta-estradiol (E2). RESULTS: E2 enhanced malignant phenotypes. Moreover, E2 treatment reduced E-cadherin expression, while increasing that of N-cadherin, vimentin, and inhibitor of differentiation 1 proteins that are associated with the epithelial-mesenchymal transition. Cell invasion was enhanced through activation of matrix metalloproteinase-9. CONCLUSION: These results indicate that hormone therapy used in breast cancer may also be effective for ER-positive SAC. PMID- 27365382 TI - A Message from the Guest Editor. PMID- 27365381 TI - Genome-wide microRNA Expression Profiling in Primary Tumors and Matched Liver Metastasis of Patients with Colorectal Cancer. AB - BACKGROUND: Primary tumor spread to the liver is the major cause of disease progression and death in patients with colorectal cancer (CRC). MicroRNAs (miRNAs) are small non-coding RNAs that are involved in cancer development and progression, but their role in metastasis has not been extensively investigated. MATERIALS AND METHODS: Firstly, expression profiling of 752 miRNAs in 20 primary tumors and their corresponding liver metastases was performed. Secondly, validation of the results was carried out on an independent cohort of 66 patients with metastatic CRC using reverse transcription-quantitative polymerase chain (RT qPCR) reaction. RESULTS: In total, 33 miRNAs were found to be significantly deregulated in liver metastases compared to their primary tumors. Fifteen miRNAs were chosen for subsequent validation, which confirmed significantly reduced expression of miR-143, miR 10b, and miR-28-5p, and increased expression of miR 122, miR-122*, and miR 885-5p in the tissue of liver metastases. CONCLUSION: These results indicate that miRNAs could serve as new therapeutic targets in patients with metastatic CRC. PMID- 27365383 TI - One Client, One Team: Health system integration for leaders. AB - This article examines the implementation of the strategy and Integrated Client Care Program, a multi-level health system strategy to break down the barriers in a solid health system and a program to integrate care for populations with the most complex needs. Specific reference is made to two specialized programs, older adults with complex care needs and a palliative care program whose goal is to meet the needs of patients and their families in a community setting. PMID- 27365384 TI - Definir les choix a risque: l'ethique et les effets des decisions organisationnelles. AB - Les choix de vivre " a risque " sont complexes et difficiles. Ils peuvent etre structures par les politiques organisationnelles. Certaines personnes veulent vraiment vivre dans des situations a haut risque ou percues comme telles parce qu'elles en tirent un avantage important. Cependant, il est probable que ces choix dependent en grande partie du contexte et qu'ils ne se soient pas poses dans une autre situation. L'article plaide pour la responsabilite d'etre attentif aux effets des decisions organisationnelles sur les choix de vivre a risque et sur la repartition globale du risque. PMID- 27365386 TI - Editorial Commentary: Where to Place the New Treatments for Clostridium difficile Infection? PMID- 27365385 TI - Fish-Derived Omega-3 Fatty Acids and Prostate Cancer: A Systematic Review. AB - BACKGROUND: The use of natural health products in prostate cancer (PrCa) is high despite a lack of evidence with respect to safety and efficacy. Fish-derived omega-3 fatty acids possess anti-inflammatory effects and preclinical data suggest a protective effect on PrCa incidence and progression; however, human studies have yielded conflicting results. METHODS: A search of OVID MEDLINE, Pre MEDLINE, Embase, and the Allied and Complementary Medicine Database (AMED) was completed for human interventional or observational data assessing the safety and efficacy of fish-derived omega-3 fatty acids in the incidence and progression of PrCa. RESULTS: Of 1776 citations screened, 54 publications reporting on 44 studies were included for review and analysis: 4 reports of 3 randomized controlled trials, 1 nonrandomized clinical trial, 20 reports of 14 cohort studies, 26 reports of 23 case-control studies, and 3 case-cohort studies. The interventional studies using fish oil supplements in patients with PrCa showed no impact on prostate-specific antigen levels; however, 2 studies showed a decrease in inflammatory or other cancer markers. A small number of mild adverse events were reported and interactions with other interventions were not assessed. Cohort and case-control studies assessing the relationship between dietary fish intake and the risk of PrCa were equivocal. Cohort studies assessing the risk of PrCa mortality suggested an association between higher intake of fish and decreased risk of prostate cancer-related death. CONCLUSIONS: Current evidence is insufficient to suggest a relationship between fish-derived omega-3 fatty acid and risk of PrCa. An association between higher omega-3 intake and decreased PrCa mortality may be present but more research is needed. More intervention trials or observational studies with precisely measured exposure are needed to assess the impact of fish oil supplements and dietary fish-derived omega-3 fatty acid intake on safety, PrCa incidence, treatment, and progression. PMID- 27365387 TI - Antibodies to Toxin B Are Protective Against Clostridium difficile Infection Recurrence. AB - BACKGROUND: Although newer studies have evaluated risk factors for recurrent Clostridium difficile infection (CDI), the vast majority did not measure important biomarkers such as endogenous anti-toxin A and anti-toxin B antibody levels. METHODS: Data from the placebo group of a phase 2 trial testing monoclonal antibodies to C. difficile toxins A and B for preventing CDI recurrence (rCDI) were analyzed to assess risk factors associated with rCDI. Patients with symptomatic CDI taking metronidazole or vancomycin were enrolled. The primary outcome was rCDI within 84 days of treatment start. Univariate and multivariate logistic regression was used to examine associations between potential risk factors and rCDI. At baseline, demographic and clinical characteristics were recorded; endogenous antibody levels were assessed using 2 enzyme-linked immunosorbent assays. RESULTS: A predictor of recurrence was age >=65 years, and an antibody-mediated immune response to toxin B appears to be protective against rCDI. CONCLUSIONS: Our findings demonstrate the importance of clinical as well as immunological risk factors in rCDI and provide more robust evidence for the protective effects of antibody to toxin B in the prevention of rCDI. CLINICAL TRIALS REGISTRATION: NCT00350298. PMID- 27365389 TI - August 2016 Update. PMID- 27365390 TI - MicroRNA-30c Mimic Mitigates Hypercholesterolemia and Atherosclerosis in Mice. AB - High plasma cholesterol levels are a major risk factor for atherosclerosis. Plasma cholesterol can be reduced by inhibiting lipoprotein production; however, this is associated with steatosis. Previously we showed that lentivirally mediated hepatic expression of microRNA-30c (miR-30c) reduced hyperlipidemia and atherosclerosis in mice without causing hepatosteatosis. Because viral therapy would be formidable, we examined whether a miR-30c mimic can be used to mitigate hyperlipidemia and atherosclerosis without inducing steatosis. Delivery of a miR 30c mimic to the liver diminished diet-induced hypercholesterolemia in C57BL/6J mice. Reductions in plasma cholesterol levels were significantly correlated with increases in hepatic miR-30c levels. Long term dose escalation studies showed that miR-30c mimic caused sustained reductions in plasma cholesterol with no obvious side effects. Furthermore, miR-30c mimic significantly reduced hypercholesterolemia and atherosclerosis in Apoe(-/-) mice. Mechanistic studies showed that miR-30c mimic had no effect on LDL clearance but reduced lipoprotein production by down-regulating microsomal triglyceride transfer protein expression. MiR-30c had no effect on fatty acid oxidation but reduced lipid synthesis. Additionally, whole transcriptome analysis revealed that miR-30c mimic significantly down-regulated hepatic lipid synthesis pathways. Therefore, miR-30c lowers plasma cholesterol and mitigates atherosclerosis by reducing microsomal triglyceride transfer protein expression and lipoprotein production and avoids steatosis by diminishing lipid syntheses. It mitigates atherosclerosis most likely by reducing lipoprotein production and plasma cholesterol. These findings establish that increasing hepatic miR-30c levels is a viable treatment option for reducing hypercholesterolemia and atherosclerosis. PMID- 27365391 TI - A Conserved Ectodomain-Transmembrane Domain Linker Motif Tunes the Allosteric Regulation of Cell Surface Receptors. AB - In many families of cell surface receptors, a single transmembrane (TM) alpha helix separates ecto- and cytosolic domains. A defined coupling of ecto- and TM domains must be essential to allosteric receptor regulation but remains little understood. Here, we characterize the linker structure, dynamics, and resulting ecto-TM domain coupling of integrin alphaIIb in model constructs and relate it to other integrin alpha subunits by mutagenesis. Cellular integrin activation assays subsequently validate the findings in intact receptors. Our results indicate a flexible yet carefully tuned ecto-TM coupling that modulates the signaling threshold of integrin receptors. Interestingly, a proline at the N-terminal TM helix border, termed NBP, is critical to linker flexibility in integrins. NBP is further predicted in 21% of human single-pass TM proteins and validated in cytokine receptors by the TM domain structure of the cytokine receptor common subunit beta and its P441A-substituted variant. Thus, NBP is a conserved uncoupling motif of the ecto-TM domain transition and the degree of ecto-TM domain coupling represents an important parameter in the allosteric regulation of diverse cell surface receptors. PMID- 27365392 TI - Escherichia coli Topoisomerase IV E Subunit and an Inhibitor Binding Mode Revealed by NMR Spectroscopy. AB - Bacterial topoisomerases are attractive antibacterial drug targets because of their importance in bacterial growth and low homology with other human topoisomerases. Structure-based drug design has been a proven approach of efficiently developing new antibiotics against these targets. Past studies have focused on developing lead compounds against the ATP binding pockets of both DNA gyrase and topoisomerase IV. A detailed understanding of the interactions between ligand and target in a solution state will provide valuable information for further developing drugs against topoisomerase IV targets. Here we describe a detailed characterization of a known potent inhibitor containing a 9H pyrimido[4,5-b]indole scaffold against the N-terminal domain of the topoisomerase IV E subunit from Escherichia coli (eParE). Using a series of biophysical and biochemical experiments, it has been demonstrated that this inhibitor forms a tight complex with eParE. NMR studies revealed the exact protein residues responsible for inhibitor binding. Through comparative studies of two inhibitors of markedly varied potencies, it is hypothesized that gaining molecular interactions with residues in the alpha4 and residues close to the loop of beta1 alpha2 and residues in the loop of beta3-beta4 might improve the inhibitor potency. PMID- 27365393 TI - Phosphorylation of Leukotriene C4 Synthase at Serine 36 Impairs Catalytic Activity. AB - Leukotriene C4 synthase (LTC4S) catalyzes the formation of the proinflammatory lipid mediator leukotriene C4 (LTC4). LTC4 is the parent molecule of the cysteinyl leukotrienes, which are recognized for their pathogenic role in asthma and allergic diseases. Cellular LTC4S activity is suppressed by PKC-mediated phosphorylation, and recently a downstream p70S6k was shown to play an important role in this process. Here, we identified Ser(36) as the major p70S6k phosphorylation site, along with a low frequency site at Thr(40), using an in vitro phosphorylation assay combined with mass spectrometry. The functional consequences of p70S6k phosphorylation were tested with the phosphomimetic mutant S36E, which displayed only about 20% (20 MUmol/min/mg) of the activity of WT enzyme (95 MUmol/min/mg), whereas the enzyme activity of T40E was not significantly affected. The enzyme activity of S36E increased linearly with increasing LTA4 concentrations during the steady-state kinetics analysis, indicating poor lipid substrate binding. The Ser(36) is located in a loop region close to the entrance of the proposed substrate binding pocket. Comparative molecular dynamics indicated that Ser(36) upon phosphorylation will pull the first luminal loop of LTC4S toward the neighboring subunit of the functional homotrimer, thereby forming hydrogen bonds with Arg(104) in the adjacent subunit. Because Arg(104) is a key catalytic residue responsible for stabilization of the glutathione thiolate anion, this phosphorylation-induced interaction leads to a reduction of the catalytic activity. In addition, the positional shift of the loop and its interaction with the neighboring subunit affect active site access. Thus, our mutational and kinetic data, together with molecular simulations, suggest that phosphorylation of Ser(36) inhibits the catalytic function of LTC4S by interference with the catalytic machinery. PMID- 27365394 TI - The Central Polybasic Region of the Soluble SNARE (Soluble N-Ethylmaleimide sensitive Factor Attachment Protein Receptor) Vam7 Affects Binding to Phosphatidylinositol 3-Phosphate by the PX (Phox Homology) Domain. AB - The yeast vacuole requires four SNAREs to trigger membrane fusion including the soluble Qc-SNARE Vam7. The N-terminal PX domain of Vam7 binds to the lipid phosphatidylinositol 3-phosphate (PI3P) and the tethering complex HOPS (homotypic fusion and vacuole protein sorting complex), whereas the C-terminal SNARE motif forms SNARE complexes. Vam7 also contains an uncharacterized middle domain that is predicted to be a coiled-coil domain with multiple helices. One helix contains a polybasic region (PBR) composed of Arg-164, Arg-168, Lys-172, Lys-175, Arg-179, and Lys-186. Polybasic regions are often associated with nonspecific binding to acidic phospholipids including phosphoinositides. Although the PX (phox homology) domain alone binds PI3P, we theorized that the Vam7 PBR could bind to additional acidic phospholipids enriched at fusion sites. Mutating each of the basic residues in the PBR to an alanine (Vam7-6A) led to attenuated vacuole fusion. The defective fusion of Vam7-6A was due in part to inefficient association with its cognate SNAREs and HOPS, yet the overall vacuole association of Vam7-6A was similar to wild type. Experiments testing the binding of Vam7 to specific signaling lipids showed that mutating the PBR to alanines augmented binding to PI3P. The increased binding to PI3P by Vam7-6A likely contributed to the observed wild type levels of vacuole association, whereas protein-protein interactions were diminished. PI3P binding was inhibited when the PX domain mutant Y42A was introduced into Vam7-6A to make Vam7-7A. Thus the Vam7 PBR affects PI3P binding by the PX domain and in turn affects binding to SNAREs and HOPS to support efficient fusion. PMID- 27365395 TI - Heme-dependent Metabolite Switching Regulates H2S Synthesis in Response to Endoplasmic Reticulum (ER) Stress. AB - Substrate ambiguity and relaxed reaction specificity underlie the diversity of reactions catalyzed by the transsulfuration pathway enzymes, cystathionine beta synthase (CBS) and gamma-cystathionase (CSE). These enzymes either commit sulfur metabolism to cysteine synthesis from homocysteine or utilize cysteine and/or homocysteine for synthesis of H2S, a signaling molecule. We demonstrate that a kinetically controlled heme-dependent metabolite switch in CBS regulates these competing reactions where by cystathionine, the product of CBS, inhibits H2S synthesis by the second enzyme, CSE. Under endoplasmic reticulum stress conditions, induction of CSE and up-regulation of the CBS inhibitor, CO, a product of heme oxygenase-1, flip the operating preference of CSE from cystathionine to cysteine, transiently stimulating H2S production. In contrast, genetic deficiency of CBS leads to chronic stimulation of H2S production. This metabolite switch from cystathionine to cysteine and/or homocysteine renders H2S synthesis by CSE responsive to the known modulators of CBS: S-adenosylmethionine, NO, and CO. Used acutely, it regulates H2S synthesis; used chronically, it might contribute to disease pathology. PMID- 27365396 TI - Structural Mechanism for Light-driven Transport by a New Type of Chloride Ion Pump, Nonlabens marinus Rhodopsin-3. AB - The light-driven inward chloride ion-pumping rhodopsin Nonlabens marinus rhodopsin-3 (NM-R3), from a marine flavobacterium, belongs to a phylogenetic lineage distinct from the halorhodopsins known as archaeal inward chloride ion pumping rhodopsins. NM-R3 and halorhodopsin have distinct motif sequences that are important for chloride ion binding and transport. In this study, we present the crystal structure of a new type of light-driven chloride ion pump, NM-R3, at 1.58 A resolution. The structure revealed the chloride ion translocation pathway and showed that a single chloride ion resides near the Schiff base. The overall structure, chloride ion-binding site, and translocation pathway of NM-R3 are different from those of halorhodopsin. Unexpectedly, this NM-R3 structure is similar to the crystal structure of the light-driven outward sodium ion pump, Krokinobacter eikastus rhodopsin 2. Structural and mutational analyses of NM-R3 revealed that most of the important amino acid residues for chloride ion pumping exist in the ion influx region, located on the extracellular side of NM-R3. In contrast, on the opposite side, the cytoplasmic regions of K. eikastus rhodopsin 2 were reportedly important for sodium ion pumping. These results provide new insight into ion selection mechanisms in ion pumping rhodopsins, in which the ion influx regions of both the inward and outward pumps are important for their ion selectivities. PMID- 27365397 TI - The Molecular Chaperone Hsc70 Interacts with Tyrosine Hydroxylase to Regulate Enzyme Activity and Synaptic Vesicle Localization. AB - We previously reported that the vesicular monoamine transporter 2 (VMAT2) is physically and functionally coupled with Hsc70 as well as with the dopamine synthesis enzymes tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase, providing a novel mechanism for dopamine homeostasis regulation. Here we expand those findings to demonstrate that Hsc70 physically and functionally interacts with TH to regulate the enzyme activity and synaptic vesicle targeting. Co-immunoprecipitation assays performed in brain tissue and heterologous cells demonstrated that Hsc70 interacts with TH and aromatic amino acid decarboxylase. Furthermore, in vitro binding assays showed that TH directly binds the substrate binding and carboxyl-terminal domains of Hsc70. Immunocytochemical studies indicated that Hsc70 and TH co-localize in midbrain dopaminergic neurons. The functional significance of the Hsc70-TH interaction was then investigated using TH activity assays. In both dopaminergic MN9D cells and mouse brain synaptic vesicles, purified Hsc70 facilitated an increase in TH activity. Neither the closely related protein Hsp70 nor the unrelated Hsp60 altered TH activity, confirming the specificity of the Hsc70 effect. Overexpression of Hsc70 in dopaminergic MN9D cells consistently resulted in increased TH activity whereas knockdown of Hsc70 by short hairpin RNA resulted in decreased TH activity and dopamine levels. Finally, in cells with reduced levels of Hsc70, the amount of TH associated with synaptic vesicles was decreased. This effect was rescued by addition of purified Hsc70. Together, these data demonstrate a novel interaction between Hsc70 and TH that regulates the activity and localization of the enzyme to synaptic vesicles, suggesting an important role for Hsc70 in dopamine homeostasis. PMID- 27365388 TI - Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. AB - It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. PMID- 27365398 TI - FBXO3 Protein Promotes Ubiquitylation and Transcriptional Activity of AIRE (Autoimmune Regulator). AB - The autoimmune regulator (AIRE) is a transcription factor which is expressed in medullary thymic epithelial cells. It directs the expression of otherwise tissue specific antigens, which leads to the elimination of autoreactive T cells during development. AIRE is modified post-translationally by phosphorylation and ubiquitylation. In this report we connected these modifications. AIRE, which is phosphorylated on two specific residues near its N terminus, then binds to the F box protein 3 (FBXO3) E3 ubiquitin ligase. In turn, this SCF(FBXO3) (SKP1-CUL1-F box) complex ubiquitylates AIRE, increases its binding to the positive transcription elongation factor b (P-TEFb), and potentiates its transcriptional activity. Because P-TEFb is required for the transition from initiation to elongation of transcription, this interaction ensures proper expression of AIRE responsive tissue-specific antigens in the thymus. PMID- 27365399 TI - 20-Hydroxyecdysone (20E) Primary Response Gene E75 Isoforms Mediate Steroidogenesis Autoregulation and Regulate Developmental Timing in Bombyx. AB - The temporal control mechanisms that precisely control animal development remain largely elusive. The timing of major developmental transitions in insects, including molting and metamorphosis, is coordinated by the steroid hormone 20 hydroxyecdysone (20E). 20E involves feedback loops to maintain pulses of ecdysteroid biosynthesis leading to its upsurge, whereas the underpinning molecular mechanisms are not well understood. Using the silkworm Bombyx mori as a model, we demonstrated that E75, the 20E primary response gene, mediates a regulatory loop between ecdysteroid biosynthesis and 20E signaling. E75 isoforms A and C directly bind to retinoic acid receptor-related response elements in Halloween gene promoter regions to induce gene expression thus promoting ecdysteroid biosynthesis and developmental transition, whereas isoform B antagonizes the transcriptional activity of isoform A/C through physical interaction. As the expression of E75 isoforms is differentially induced by 20E, the E75-mediated regulatory loop represents a fine autoregulation of steroidogenesis, which contributes to the precise control of developmental timing. PMID- 27365400 TI - Discovery Proteomics Identifies a Molecular Link between the Coatomer Protein Complex I and Androgen Receptor-dependent Transcription. AB - Aberrant androgen receptor (AR)-dependent transcription is a hallmark of human prostate cancers. At the molecular level, ligand-mediated AR activation is coordinated through spatial and temporal protein-protein interactions involving AR-interacting proteins, which we designate the "AR-interactome." Despite many years of research, the ligand-sensitive protein complexes involved in ligand mediated AR activation in prostate tumor cells have not been clearly defined. Here, we describe the development, characterization, and utilization of a novel human LNCaP prostate tumor cell line, N-AR, which stably expresses wild-type AR tagged at its N terminus with the streptavidin-binding peptide epitope (streptavidin-binding peptide-tagged wild-type androgen receptor; SBP-AR). A bioanalytical workflow involving streptavidin chromatography and label-free quantitative mass spectrometry was used to identify SBP-AR and associated ligand sensitive cytosolic proteins/protein complexes linked to AR activation in prostate tumor cells. Functional studies verified that ligand-sensitive proteins identified in the proteomic screen encoded modulators of AR-mediated transcription, suggesting that these novel proteins were putative SBP-AR interacting proteins in N-AR cells. This was supported by biochemical associations between recombinant SBP-AR and the ligand-sensitive coatomer protein complex I (COPI) retrograde trafficking complex in vitro Extensive biochemical and molecular experiments showed that the COPI retrograde complex regulates ligand-mediated AR transcriptional activation, which correlated with the mobilization of the Golgi-localized ARA160 coactivator to the nuclear compartment of prostate tumor cells. Collectively, this study provides a bioanalytical strategy to validate the AR-interactome and define novel AR-interacting proteins involved in ligand-mediated AR activation in prostate tumor cells. Moreover, we describe a cellular system to study how compartment-specific AR-interacting proteins influence AR activation and contribute to aberrant AR-dependent transcription that underlies the majority of human prostate cancers. PMID- 27365401 TI - Hook Adaptors Induce Unidirectional Processive Motility by Enhancing the Dynein Dynactin Interaction. AB - Cytoplasmic dynein drives the majority of minus end-directed vesicular and organelle motility in the cell. However, it remains unclear how dynein is spatially and temporally regulated given the variety of cargo that must be properly localized to maintain cellular function. Recent work has suggested that adaptor proteins provide a mechanism for cargo-specific regulation of motors. Of particular interest, studies in fungal systems have implicated Hook proteins in the regulation of microtubule motors. Here we investigate the role of mammalian Hook proteins, Hook1 and Hook3, as potential motor adaptors. We used optogenetic approaches to specifically recruit Hook proteins to organelles and observed rapid transport of peroxisomes to the perinuclear region of the cell. This rapid and efficient translocation of peroxisomes to microtubule minus ends indicates that mammalian Hook proteins activate dynein rather than kinesin motors. Biochemical studies indicate that Hook proteins interact with both dynein and dynactin, stabilizing the formation of a supramolecular complex. Complex formation requires the N-terminal domain of Hook proteins, which resembles the calponin-homology domain of end-binding (EB) proteins but cannot bind directly to microtubules. Single-molecule motility assays using total internal reflection fluorescence microscopy indicate that both Hook1 and Hook3 effectively activate cytoplasmic dynein, inducing longer run lengths and higher velocities than the previously characterized dynein activator bicaudal D2 (BICD2). Together, these results suggest that dynein adaptors can differentially regulate dynein to allow for organelle-specific tuning of the motor for precise intracellular trafficking. PMID- 27365402 TI - Loss of Macrophage Low-Density Lipoprotein Receptor-Related Protein 1 Confers Resistance to the Antiatherogenic Effects of Tumor Necrosis Factor-alpha Inhibition. AB - OBJECTIVE: Antiatherosclerotic effects of tumor necrosis factor-alpha (TNF-alpha) blockade in patients with systemic inflammatory states are not conclusively demonstrated, which suggests that effects depend on the cause of inflammation. Macrophage LRP1 (low-density lipoprotein receptor-related protein 1) and apoE contribute to inflammation through different pathways. We studied the antiatherosclerosis effects of TNF-alpha blockade in hyperlipidemic mice lacking either LRP1 (MPhiLRP1(-/-)) or apoE from macrophages. APPROACH AND RESULTS: Lethally irradiated low-density lipoprotein receptor (LDLR)(-/-) mice were reconstituted with bone marrow from either wild-type, MPhiLRP1(-/-), apoE(-/-) or apoE(-/-)/MPhiLRP1(-/-)(DKO) mice, and then treated with the TNF-alpha inhibitor adalimumab while fed a Western-type diet. Adalimumab reduced plasma TNF-alpha concentration, suppressed blood ly6C(hi) monocyte levels and their migration into the lesion, and reduced lesion cellularity and inflammation in both wild-type >LDLR(-/-) and apoE(-/-)->LDLR(-/-) mice. Overall, adalimumab reduced lesion burden by 52% to 57% in these mice. Adalimumab reduced TNF-alpha and blood ly6C(hi) monocyte levels in MPhiLRP1(-/-)->LDLR(-/-) and DKO->LDLR(-/-) mice, but it did not suppress ly6C(hi) monocyte migration into the lesion or atherosclerosis progression. CONCLUSIONS: Our results show that TNF-alpha blockade exerts antiatherosclerotic effects that are dependent on the presence of macrophage LRP1. PMID- 27365403 TI - Serum Angiopoietin-Like Protein 2 Is a Novel Risk Factor for Cardiovascular Disease in the Community: The Hisayama Study. AB - OBJECTIVE: Angiopoietin-like protein 2 (ANGPTL2), a proinflammatory mediator, has been reported to accelerate the development of insulin resistance, endothelial dysfunction, and atherosclerosis in mice. However, no cohort studies have examined the relationship between serum ANGPTL2 levels and the development of cardiovascular disease (CVD) in a general population. APPROACH AND RESULTS: A total of 3005 community-dwelling Japanese aged >=40 years without a history of CVD were divided into 4 groups according to the quartiles of serum ANGPTL2 concentrations (Q1, lowest and Q4, highest) and followed up for 10 years. The hazards ratios and their 95% confidence intervals for the development of CVD (coronary heart disease or stroke) were estimated using a Cox proportional hazards model. During the follow-up, 219 first-ever CVD events were observed. The risk of CVD increased significantly with elevating ANGPTL2 levels after adjustment for age, sex, serum total cholesterol, use of lipid-lowering agents, ECG abnormalities, smoking habits, alcohol intake, and regular exercise (hazards ratios [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.27 [0.80-2.04]; Q3, 1.48 [0.95-2.32]; and Q4, 1.85 [1.20-2.85]; P=0.003 for trend). After additional adjustment for metabolic syndrome components and serum high-sensitivity C reactive protein levels as an inflammatory marker, the association was attenuated but remained significant (hazards ratios [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.21 [0.76-1.94]; Q3, 1.38 [0.87-2.17]; and Q4, 1.66 [1.05 2.60]; P=0.02 for trend). CONCLUSIONS: Our findings suggest that elevated serum ANGPTL2 levels are a novel risk factor for the development of CVD in the general population. This association is partially mediated by metabolic disorders and inflammation. PMID- 27365404 TI - Role of Axl in T-Lymphocyte Survival in Salt-Dependent Hypertension. AB - OBJECTIVE: Survival of immune and nonimmune cells relies on Axl, a receptor tyrosine kinase, which is implicated in hypertension. Activated T lymphocytes are involved in regulation of high blood pressure. The goal of the study was to investigate the role of Axl in T-lymphocyte functions and its contribution to salt-dependent hypertension. APPROACH AND RESULTS: We report increased apoptosis in peripheral blood from Axl(-/-) mice because of lower numbers of white blood cells mostly lymphocytes. In vitro studies showed modest reduction in interferon gamma production in Axl(-/-) type 1 T helper cells. Axl did not affect basic proliferation capacity or production of interleukin 4 in Axl(-/-) type 2 T helper cells. However, competitive repopulation of Axl(-/-) bone marrow or adoptive transfer of Axl(-/-) CD4(+) T cells to Rag1(-/-) mice showed robust effect of Axl on T lymphocyte expansion in vivo. Adoptive transfer of Axl(-/-) CD4(+) T cells was protective in a later phase of deoxycorticosterone-acetate and salt hypertension. Reduced numbers of CD4(+) T cells in circulation and in perivascular adventitia decreased vascular remodeling and increased vascular apoptosis in the late phase of hypertension. CONCLUSIONS: These findings suggest that Axl is critical for survival of T lymphocytes, especially during vascular remodeling in hypertension. PMID- 27365405 TI - Smooth Muscle Cell-Derived Interleukin-17C Plays an Atherogenic Role via the Recruitment of Proinflammatory Interleukin-17A+ T Cells to the Aorta. AB - OBJECTIVE: Atherosclerosis is characterized by frequent communication between infiltrating leukocytes and vascular cells, through chemokine and cytokine networks. Interleukin-17C (IL-17C) is detectable within atherosclerotic lesions; however, the potential involvement of this cytokine has not been examined. Thus, we sought to investigate the role of IL-17C in atherosclerosis. APPROACH AND RESULTS: The expression of IL-17 cytokines was profiled within aortas of apolipoprotein E double knockout (Apoe(-/-)) mice, and Il17c expression was elevated. Flow cytometry experiments revealed a major population of aortic IL-17C producing smooth muscle cells. Next, we generated Il17c(-/-)Apoe(-/-) mice and demonstrated that atherosclerotic lesion and collagen content was diminished within Western diet-fed Il17c(-/-)Apoe(-/-) aortas and aortic roots in comparison to Apoe(-/-) controls. Smooth muscle cells and fibroblasts were mainly responsible for the reduced Col1A1 expression in the aorta of Il17c(-/-)Apoe(-/-) mice. Importantly, IL-17C-treated Apoe(-/-) aortas showed upregulated Col1A1 expression ex vivo. Il17c(-/-)Apoe(-/-) mice displayed a proportional reduction in aortic macrophages, neutrophils, T cells, T helper 1 cells, and T regulatory cells, without corresponding changes in the peripheral immune composition. Examination of aortic IL-17A(+) T-cell receptor gammadelta T cells and Th17 cells demonstrated a stark reduction in the percentage and number of these subsets within Il17c(-/-)Apoe(-/-) versus Apoe(-/-) mice. Explanted 12-week Western diet fed Apoe(-/-) aortas treated with IL-17C resulted in the induction of multiple vascular chemokines and cytokines. Th17 cells demonstrated attenuated migration toward supernatants from cultures of Il17c(-/-)Apoe(-/-) smooth muscle cells, and short-term homing experiments revealed diminished recruitment of Th17 cells to the aorta of Il17c(-/-)Apoe(-/-) recipients. CONCLUSIONS: Smooth muscle cell derived IL-17C plays a proatherogenic role by supporting the recruitment of Th17 cells to atherosclerotic lesions. PMID- 27365407 TI - Association of Skin Autofluorescence Levels With Kidney Function Decline in Patients With Peripheral Artery Disease. AB - OBJECTIVE: Skin autofluorescence (SAF), a measure of advanced glycation end product accumulation, is associated with kidney function. We investigated the association of SAF with rate of kidney function decline in a cohort of patients with peripheral artery disease. APPROACH AND RESULTS: We performed a post hoc analysis of an observational longitudinal cohort study. We included 471 patients with peripheral artery disease, and SAF was measured at baseline. Primary end point was rate of estimated glomerular filtration rate (eGFR) decline. Secondary end points were incidence of eGFR <60 and <45 mL/min/1.73 m(2) and rapid eGFR decline, defined as a decrease in eGFR of >5 mL/min/1.73 m(2)/y. During a median follow-up of 3 years, the mean change in eGFR per year was -1.8+/-4.4 mL/min/1.73 m(2)/y. No significant difference in rate of eGFR decline was observed per 1 arbitrary unit increase in SAF (-0.1 mL/min/1.73 m(2)/y; 95% confidence interval, -0.7 to 0.5; P=0.8). Analyses of the secondary end points showed that there was an association of SAF with incidence of eGFR <60 and <45 mL/min/1.73 m(2) (hazard ratio, 1.54; 95% confidence interval, 1.13-2.10; P=0.006 and hazard ratio, 1.76; 95% confidence interval, 1.20-2.59; P=0.004, respectively), but after adjustment for age and sex, significance was lost. There was no association of SAF with rapid eGFR decline. CONCLUSIONS: In conclusion, in this cohort of patients with peripheral artery disease, elevated SAF was associated with lower baseline eGFR. Although SAF has previously been established as a predictor for cardiovascular disease and mortality, it did not predict the rate of kidney function decline during follow-up in this study. PMID- 27365408 TI - Whang J, Frei E III, Tjio JH, Carbone PP, Brecher G. The distribution of the Philadelphia chromosome in patients with chronic myelogenous leukemia. Blood. 1963;22(6):664-673. PMID- 27365406 TI - Cathepsin S Activity Controls Injury-Related Vascular Repair in Mice via the TLR2 Mediated p38MAPK and PI3K-Akt/p-HDAC6 Signaling Pathway. AB - OBJECTIVE: Cathepsin S (CatS) participates in atherogenesis through several putative mechanisms. The ability of cathepsins to modify histone tail is likely to contribute to stem cell development. Histone deacetylase 6 (HDAC6) is required in modulating the proliferation and migration of various types of cancer cells. Here, we investigated the cross talk between CatS and HADC6 in injury-related vascular repair in mice. APPROACH AND RESULTS: Ligation injury to the carotid artery in mice increased the CatS expression, and CatS-deficient mice showed reduced neointimal formation in injured arteries. CatS deficiency decreased the phosphorylation levels of p38 mitogen-activated protein kinase, Akt, and HDAC6 and toll-like receptor 2 expression in ligated arteries. The genetic or pharmacological inhibition of CatS also alleviated the increased phosphorylation of p38 mitogen-activated protein kinase, Akt, and HDAC6 induced by platelet derived growth factor BB in cultured vascular smooth muscle cells (VSMCs), and p38 mitogen-activated protein kinase inhibition and Akt inhibition decreased the phospho-HDAC6 levels. Moreover, CatS inhibition caused decrease in the levels of the HDAC6 activity in VSMCs in response to platelet-derived growth factor BB. The HDAC6 inhibitor tubastatin A downregulated platelet-derived growth factor-induced VSMC proliferation and migration, whereas HDAC6 overexpression exerted the opposite effect. Tubastatin A also decreased the intimal VSMC proliferation and neointimal hyperplasia in response to injury. Toll-like receptor 2 silencing decreased the phosphorylation levels of p38 mitogen-activated protein kinase, Akt, and HDAC6 and VSMC migration and proliferation. CONCLUSIONS: This is the first report detailing cross-interaction between toll-like receptor 2-mediated CatS and HDAC6 during injury-related vascular repair. These data suggest that CatS/HDAC6 could be a potential therapeutic target for the control of vascular diseases that are involved in neointimal lesion formation. PMID- 27365409 TI - EZH2: a molecular switch of the MPN phenotype. PMID- 27365410 TI - One giant leap for pediatric AMKL. PMID- 27365411 TI - Tracers for tracing neutrophils. PMID- 27365412 TI - The power of cord blood cells. PMID- 27365413 TI - Metabolic Cost of Protein Synthesis in Larvae of the Pacific Oyster (Crassostrea gigas) Is Fixed Across Genotype, Phenotype, and Environmental Temperature. AB - The energy made available through catabolism of specific biochemical reserves is constant using standard thermodynamic conversion equivalents (e.g., 24.0 J mg protein(-1)). In contrast, measurements reported for the energy cost of synthesis of specific biochemical constituents are highly variable. In this study, we measured the metabolic cost of protein synthesis and determined whether this cost was influenced by genotype, phenotype, or environment. We focused on larval stages of the Pacific oyster Crassostrea gigas, a species that offers several experimental advantages: availability of genetically pedigreed lines, manipulation of ploidy, and tractability of larval forms for in vivo studies of physiological processes. The cost of protein synthesis was measured in larvae of C. gigas for 1) multiple genotypes, 2) phenotypes with different growth rates, and 3) different environmental temperatures. For all treatments, the cost of protein synthesis was within a narrow range--near the theoretical minimum--with a fixed cost (mean +/- one standard error, n = 21) of 2.1 +/- 0.2 J (mg protein synthesized)(-1) We conclude that there is no genetic variation in the metabolic cost of protein synthesis, thereby simplifying bioenergetic models. Protein synthesis is a major component of larval metabolism in C. gigas, accounting for more than half the metabolic rate in diploid (59%) and triploid larvae (54%). These results provide measurements of metabolic cost of protein synthesis in larvae of C. gigas, an indicator species for impacts of ocean change, and provide a quantitative basis for evaluating the cost of resilience. PMID- 27365414 TI - Maternal Lipid Provisioning Mirrors Evolution of Reproductive Strategies in Direct-Developing Whelks. AB - The energetic input that offspring receive from their mothers is a well-studied maternal effect that can influence the evolution of life histories. Using the offspring of three sympatric whelks: Cominella virgata (one embryo per capsule); Cominella maculosa (multiple embryos per capsule); and Haustrum scobina (multiple embryos per capsule and nurse-embryo consumption), we examined how contrasting reproductive strategies mediate inter- and intraspecific differences in hatchling provisioning. Total lipid content (as measured in MUg hatchling(-1) +/- SE) was unrelated to size among the 3 species; the hatchlings of H. scobina were the smallest but had the highest lipid content (33.8 +/- 8.1 MUg hatchling(-1)). In offspring of C. maculosa, lipid content was 6.6 +/- 0.4 MUg hatchling(-1), and in offspring of C. virgata, it was 21.7 +/- 3.2 MUg hatchling(-1) The multi encapsulated hatchlings of C. maculosa and H. scobina were the only species that contained the energetic lipids, wax ester (WE) and methyl ester (ME). However, the overall composition of energetic lipid between hatchlings of the two Cominella species reflected strong affinities of taxonomy, suggesting a phylogenetic evolution of the non-adelphophagic development strategy. Inter- and intracapsular variability in sibling provisioning was highest in H. scobina, a finding that implies less control of allocation to individual hatchlings in this adelphophagic developer. We suggest that interspecific variability of lipids offers a useful approach to understanding the evolution of maternal provisioning in direct-developing species. PMID- 27365415 TI - Sex Determination in Bluegill Sunfish Lepomis macrochirus: Effect of Temperature on Sex Ratio of Four Geographic Strains. AB - There is increasing evidence that temperature effects on sex ratio in fish species are ubiquitous. Temperature effects on sex ratio could be influenced by parent, strain, and population, whether in fish species with temperature dependent sex determination or genetic sex determination plus temperature effects. In the present study, effects of genotype-temperature interactions on sex determination in bluegill sunfish were further investigated, based on our previous results, using four geographic strains: Hebron, Jones, Hocking, and Missouri. In the Hebron strain, the two higher-temperature treatment groups (24 degrees C and 32 degrees C) produced more males than the low-temperature treatment group (17 degrees C) from 6 days post-hatching (dph) to 90 dph. In contrast, the low-temperature treatment produced more males than the other two higher-temperature treatments in the Jones strain. No significant effects of temperature on sex ratio were detected in the other two strains. Our results from sex ratio variance in different treatment times suggest that the thermosensitive period of sex differentiation occurs prior to 40 dph. Our results further confirmed that genotype-temperature interactions influence sex determination in bluegill. Therefore, to significantly increase the proportion of males, which grow faster and larger than females, a consumer- and environment-friendly approach may be achieved through selection of temperature sensitivity in bluegill. PMID- 27365416 TI - Complexity of Yolk Proteins and Their Dynamics in the Sea Star Patiria miniata. AB - Oviparous animals store yolk proteins within the developing oocyte. These proteins are used in gametogenesis and as a nutritional source for embryogenesis. Vitellogenin and the major yolk protein are two of the most important yolk proteins among diverse species of invertebrates and vertebrates. Among the echinoderms, members of the subphyla Echinozoa (sea urchins and sea cucumbers) express the major yolk protein (MYP) but not vitellogenin (Vtg), while an initial report has documented that two Asterozoa (sea stars) express a vitellogenin. Our results show that sea stars contain two vitellogenins, Vtg 1 and Vtg 2, and MYP. In Patiria miniata, these genes are differentially expressed in the somatic and germ cells of the ovary: Vtg 1 is enriched in the somatic cells of the ovary but not in the oocytes, and Vtg 2 accumulates in both oocytes and somatic cells; MYP is not robustly present in either. Remarkably, Vtg 2 and MYP mRNA reappear in larvae; Vtg 2 is detected within cells of the ectoderm, and MYP accumulates in the coelomic pouches, the intestine, and the posterior enterocoel (PE), the site of germ line formation in this animal. Additionally, the Vtg 2 protein is present in oocytes, follicle cells, and developing embryos, but becomes undetectable following gastrulation. These results help elucidate the mechanisms involved in yolk dynamics, and provide molecular information that allows for greater understanding of the evolution of these important gene products. PMID- 27365417 TI - Aquaporin in Chondrosia reniformis Nardo, 1847 and Its Possible Role in the Interaction Between Cells and Engulfed Siliceous Particles. AB - The sponge Chondrosia reniformis selectively engulfs siliceous particles that, when in crystalline form, become quickly dissolved in its ectosome. The molecular mechanism, identity, and physiological significance of the cells involved in this process are not completely understood. In the present study, we applied light and electronic microscopic techniques to show how the quartz particles in C. reniformis are enveloped through collagen fibers and host cells near the surface of these organisms. As various aquaporins from bacteria, animals, and plants bidirectionally conduct metalloids-including silicon ions--through the cell membrane, the presence and potential involvement of aquaporins in quartz dissolution in C. reniformis have been investigated. An aquaporin-like transcript (CrAQP) was isolated according to the transcriptome sequencing results in C. reniformis The full-length CrAQP cDNA is 907 nucleotides long, with a 795-base pair (bp), open reading frame encoding a protein of 265 amino acids, a 29-bp, 5' non-coding region, and a 83-bp, 3'-untranslated region. The Bayesian phylogenetic inference suggests that CrAqp is closely related to the Aqp8L grade, which is also implicated in H2O2 transport. Quantification of CrAQP mRNA through qPCR indicated that the transcript level was higher in the ectosome than in the choanosome. Immunofluorescence of a mammalian AQP8 in C. reniformis showed positivity in some cells near the quartz particles, a finding that may support the initial hypothesis of the potential involvement of CrAQP in quartz erosion. However, the features of the primary structure of this protein offer a new viewpoint about the functional role of these molecules in this process: that CrAQP may be involved in the permeation of H2O2 released during silica erosion. PMID- 27365418 TI - Localization of Phosphoproteins within the Barnacle Adhesive Interface. AB - Barnacles permanently adhere to nearly any inert substrate using proteinaceous glue. The glue consists of at least ten major proteins, some of which have been isolated and sequenced. Questions still remain about the chemical mechanisms involved in adhesion and the potential of the glue to serve as a platform for mineralization of the calcified base plate. We tested the hypothesis that barnacle glue contains phosphoproteins, which have the potential to play a role in both adhesion and mineralization. Using a combination of phosphoprotein specific gel staining and Western blotting with anti-phosphoserine antibody, we identified multiple phosphorylated proteins in uncured glue secretions from the barnacle Amphibalanus amphitrite The protein composition of the glue and the quantity and abundance of phosphoproteins varied distinctly among individual barnacles, possibly due to cyclical changes in the glue secretion over time. We assessed the location of the phosphoproteins within the barnacle glue layer using decalcified barnacle base plates and residual glue deposited by reattached barnacles. Phosphoproteins were found throughout the organic matrix of the base plate and within the residual glue. Staining within the residual glue appeared most intensely in regions where capillary glue ducts, which are involved in cyclical release of glue, had been laid down. Lastly, mineralization studies of glue proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) indicated that proteins identified as phosphorylated possibly induce mineralization of calcium carbonate (CaCO3). These results contribute to our understanding of the protein composition of barnacle glue, and provide new insights into the potential roles of phosphoproteins in underwater bioadhesives. PMID- 27365419 TI - Material Properties of Hagfish Skin, with Insights into Knotting Behaviors. AB - Hagfishes (Myxinidae) often integrate whole-body knotting movements with jawless biting motions when reducing large marine carcasses to ingestible items. Adaptations for these behaviors include complex arrangements of axial muscles and flexible, elongate bodies without vertebrae. Between the axial muscles and the hagfish skin is a large, blood-filled subcutaneous sinus devoid of the intricate, myoseptal tendon networks characteristic of the taut skins of other fishes. We propose that the loose-fitting skin of the hagfish facilitates the formation and manipulation of body knots, even if it is of little functional significance to steady swimming. Hagfish skin is a relatively thick, anisotropic, multilayered composite material comprising a superficial, thin, and slimy epidermis, a middle dermal layer densely packed with fibrous tissues, and a deep subdermal layer comprised of adipose tissue. Hagfish skin is stiffer when pulled longitudinally than circumferentially. Stress-strain data from uniaxial tensile tests show that hagfish skins are comparable in tensile strength and stiffness to the taut skins of elongate fishes that do not engage in knotting behaviors (e.g., sea lamprey and penpoint gunnel). Sheath-core-constructed ropes, which serve as more accurate models for hagfish bodies, demonstrate that loose skin (extra sheathing) enhances flexibility of the body (rope). Along with a loose-fitting skin, the morphologies of hagfish skin parallel those of moray eels, which are also known for generating and manipulating figure-eight-style body knots when struggling with prey. PMID- 27365420 TI - Long-term Cultivation of the Deep-Sea Clam Calyptogena okutanii: Changes in the Abundance of Chemoautotrophic Symbiont, Elemental Sulfur, and Mucus. AB - Survival of deep-sea Calyptogena clams depends on organic carbon produced by symbiotic, sulfur-oxidizing, autotrophic bacteria present in the epithelial cells of the gill. To understand the mechanism underlying this symbiosis, the development of a long-term cultivation system is essential. We cultivated specimens of Calyptogena okutanii in an artificial chemosynthetic aquarium with a hydrogen sulfide (H2S) supply system provided by the sulfate reduction of dog food buried in the sediment. We studied morphological and histochemical changes in the clams' gills by immunohistochemical and energy-dispersive X-ray analyses. The freshly collected clams contained a high amount of elemental sulfur in the gill epithelial cells, as well as densely packed symbiotic bacteria. Neither elemental sulfur nor symbiotic bacteria was detected in any other organs except the ovaries, where symbiotic bacteria, but not sulfur, was detected. The longest survival of an individual clam in this aquarium was 151 days. In the 3 clams dissected on Days 57 and 91 of the experiment, no elemental sulfur was detected in the gills. The symbiotic bacteria content had significantly decreased by Day 57, and was absent by Day 91. For comparison, we also studied the deep-sea mussel Bathymodiolus septemdierum, which harbors a phylogenetically close, sulfur oxidizing, symbiotic bacterium with similar sulfur oxidation pathways. Sulfur particles were not detected, even in the gills of the freshly collected mussels. We discuss the importance of the proportion of available H2S and oxygen to the bivalves for elemental sulfur accumulation. Storage of nontoxic elemental sulfur, an energy source, seems to be an adaptive strategy of C. okutanii. PMID- 27365423 TI - Identification of factors promoting ex vivo maintenance of mouse hematopoietic stem cells by long-term single-cell quantification. AB - The maintenance of hematopoietic stem cells (HSCs) during ex vivo culture is an important prerequisite for their therapeutic manipulation. However, despite intense research, culture conditions for robust maintenance of HSCs are still missing. Cultured HSCs are quickly lost, preventing their improved analysis and manipulation. Identification of novel factors supporting HSC ex vivo maintenance is therefore necessary. Coculture with the AFT024 stroma cell line is capable of maintaining HSCs ex vivo long-term, but the responsible molecular players remain unknown. Here, we use continuous long-term single-cell observation to identify the HSC behavioral signature under supportive or nonsupportive stroma cocultures. We report early HSC survival as a major characteristic of HSC-maintaining conditions. Behavioral screening after manipulation of candidate molecules revealed that the extracellular matrix protein dermatopontin (Dpt) is involved in HSC maintenance. DPT knockdown in supportive stroma impaired HSC survival, whereas ectopic expression of the Dpt gene or protein in nonsupportive conditions restored HSC survival. Supplementing defined stroma- and serum-free culture conditions with recombinant DPT protein improved HSC clonogenicity. These findings illustrate a previously uncharacterized role of Dpt in maintaining HSCs ex vivo. PMID- 27365422 TI - Phosphoproteomic profiling of mouse primary HSPCs reveals new regulators of HSPC mobilization. AB - Protein phosphorylation is a central mechanism of signal transduction that both positively and negatively regulates protein function. Large-scale studies of the dynamic phosphorylation states of cell signaling systems have been applied extensively in cell lines and whole tissues to reveal critical regulatory networks, and candidate-based evaluations of phosphorylation in rare cell populations have also been informative. However, application of comprehensive profiling technologies to adult stem cell and progenitor populations has been challenging, due in large part to the scarcity of such cells in adult tissues. Here, we combine multicolor flow cytometry with highly efficient 3-dimensional high performance liquid chromatography/mass spectrometry to enable quantitative phosphoproteomic analysis from 200 000 highly purified primary mouse hematopoietic stem and progenitor cells (HSPCs). Using this platform, we identify ARHGAP25 as a novel regulator of HSPC mobilization and demonstrate that ARHGAP25 phosphorylation at serine 363 is an important modulator of its function. Our approach provides a robust platform for large-scale phosphoproteomic analyses performed with limited numbers of rare progenitor cells. Data from our study comprises a new resource for understanding the molecular signaling networks that underlie hematopoietic stem cell mobilization. PMID- 27365424 TI - TNF-alpha priming enhances CD4+FoxP3+ regulatory T-cell suppressive function in murine GVHD prevention and treatment. AB - CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) have been shown to effectively prevent graft-versus-host disease (GVHD) when adoptively transferred in murine models of hematopoietic cell transplantation and in phase 1/2 clinical trials. Critical limitations to Treg clinical application are the paucity of cells and limited knowledge of the mechanisms of in vivo function. We hypothesized that inflammatory conditions in GVHD modify Treg characteristics and activity. We found that peripheral blood of recipient animals during acute GVHD (aGVHD) induces Treg activation and enhances their function. The serum contains high levels of tumor necrosis factor-alpha (TNF-alpha) that selectively activates Tregs without impacting CD4(+)FoxP3(-) T cells. TNF-alpha priming induces Treg in vivo proliferation, whereas it limits the ability of CD4 and CD8 conventional T cells (Tcons) to proliferate and induce GVHD. TNF-alpha-primed Tregs prolong animal survival as compared with unprimed Tregs when used at an unfavorable Treg:Tcon ratio, demonstrating enhanced in vivo efficacy of TNF-alpha-primed Tregs. Because TNF-alpha is produced by several immune cells during inflammation, our work elucidates aspects of the physiologic mechanisms of Treg function. Furthermore, TNF-alpha priming of Tregs provides a new tool to optimize Treg cellular therapies for GVHD prevention and treatment. PMID- 27365425 TI - A single-cell resolution map of mouse hematopoietic stem and progenitor cell differentiation. AB - Maintenance of the blood system requires balanced cell fate decisions by hematopoietic stem and progenitor cells (HSPCs). Because cell fate choices are executed at the individual cell level, new single-cell profiling technologies offer exciting possibilities for mapping the dynamic molecular changes underlying HSPC differentiation. Here, we have used single-cell RNA sequencing to profile more than 1600 single HSPCs, and deep sequencing has enabled detection of an average of 6558 protein-coding genes per cell. Index sorting, in combination with broad sorting gates, allowed us to retrospectively assign cells to 12 commonly sorted HSPC phenotypes while also capturing intermediate cells typically excluded by conventional gating. We further show that independently generated single-cell data sets can be projected onto the single-cell resolution expression map to directly compare data from multiple groups and to build and refine new hypotheses. Reconstruction of differentiation trajectories reveals dynamic expression changes associated with early lymphoid, erythroid, and granulocyte macrophage differentiation. The latter two trajectories were characterized by common upregulation of cell cycle and oxidative phosphorylation transcriptional programs. By using external spike-in controls, we estimate absolute messenger RNA (mRNA) levels per cell, showing for the first time that despite a general reduction in total mRNA, a subset of genes shows higher expression levels in immature stem cells consistent with active maintenance of the stem-cell state. Finally, we report the development of an intuitive Web interface as a new community resource to permit visualization of gene expression in HSPCs at single cell resolution for any gene of choice. PMID- 27365429 TI - EUROPE. 'Brexit' casts pall on future of U.K. science. PMID- 27365427 TI - Adsorptive depletion of blood monocytes reduces the levels of circulating interleukin-17A in Langerhans cell histiocytosis. PMID- 27365426 TI - Germ line variants predispose to both JAK2 V617F clonal hematopoiesis and myeloproliferative neoplasms. AB - We conducted a genome-wide association study (GWAS) to identify novel predisposition alleles associated with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) and JAK2 V617F clonal hematopoiesis in the general population. We recruited a web-based cohort of 726 individuals with polycythemia vera, essential thrombocythemia, and myelofibrosis and 252 637 population controls unselected for hematologic phenotypes. Using a single nucleotide polymorphism (SNP) array platform with custom probes for the JAK2 V617F mutation (V617F), we identified 497 individuals (0.2%) among the population controls who were V617F carriers. We performed a combined GWAS of the MPN cases plus V617F carriers in the control population (n = 1223) vs the remaining controls who were noncarriers for V617F (n = 252 140). For these MPN cases plus V617F carriers, we replicated the germ line JAK2 46/1 haplotype (rs59384377: odds ratio [OR] = 2.4, P = 6.6 * 10(-89)), previously associated with V617F-positive MPN. We also identified genome-wide significant associations in the TERT gene (rs7705526: OR = 1.8, P = 1.1 * 10(-32)), in SH2B3 (rs7310615: OR = 1.4, P = 3.1 * 10(-14)), and upstream of TET2 (rs1548483: OR = 2.0, P = 2.0 * 10(-9)). These associations were confirmed in a separate replication cohort of 446 V617F carriers vs 169 021 noncarriers. In a joint analysis of the combined GWAS and replication results, we identified additional genome-wide significant predisposition alleles associated with CHEK2, ATM, PINT, and GFI1B All SNP ORs were similar for MPN patients and controls who were V617F carriers. These data indicate that the same germ line variants endow individuals with a predisposition not only to MPN, but also to JAK2 V617F clonal hematopoiesis, a more common phenomenon that may foreshadow the development of an overt neoplasm. PMID- 27365431 TI - PHYSICAL SCIENCE. Researchers rise to challenge of replacing helium-3. PMID- 27365430 TI - IMMUNOLOGY. Fighting autoimmunity with immune cells. PMID- 27365433 TI - U.S. SCIENCE POLICY. Scientists cheer Senate bill. PMID- 27365432 TI - ATMOSPHERIC SCIENCE. CFC bans pay off as Antarctic ozone layer starts to mend. PMID- 27365434 TI - South Africa's bid to end AIDS. PMID- 27365436 TI - ECOLOGY. How frigate birds soar around the doldrums. PMID- 27365437 TI - PHYSICS. Timing photoemission--Final state matters. PMID- 27365438 TI - ANTHROPOLOGY. The evolutionary path of least resistance. PMID- 27365439 TI - NEUROREGENERATION. Promoting CNS repair. PMID- 27365440 TI - ECOLOGY. How climate change affects plants' sex lives. PMID- 27365441 TI - SEX DETERMINATION. Yob makes mosquitoes male. PMID- 27365442 TI - GOVERNMENT TRANSPARENCY. Reforms to improve U.S. government accountability. PMID- 27365443 TI - Catalytic, asymmetric difluorination of alkenes to generate difluoromethylated stereocenters. AB - Difluoromethyl groups possess specific steric and electronic properties that invite their use as chemically inert surrogates of alcohols, thiols, and other polar functional groups important in a wide assortment of molecular recognition processes. We report here a method for the catalytic, asymmetric, migratory geminal difluorination of beta-substituted styrenes to access a variety of products bearing difluoromethylated tertiary or quaternary stereocenters. The reaction uses commercially available reagents (m-chloroperbenzoic acid and hydrogen fluoride pyridine) and a simple chiral aryl iodide catalyst and is carried out readily on a gram scale. Substituent effects and temperature dependent variations in enantioselectivity suggest that cation-pi interactions play an important role in stereodifferentiation by the catalyst. PMID- 27365444 TI - Large wind ripples on Mars: A record of atmospheric evolution. AB - Wind blowing over sand on Earth produces decimeter-wavelength ripples and hundred meter- to kilometer-wavelength dunes: bedforms of two distinct size modes. Observations from the Mars Science Laboratory Curiosity rover and the Mars Reconnaissance Orbiter reveal that Mars hosts a third stable wind-driven bedform, with meter-scale wavelengths. These bedforms are spatially uniform in size and typically have asymmetric profiles with angle-of-repose lee slopes and sinuous crest lines, making them unlike terrestrial wind ripples. Rather, these structures resemble fluid-drag ripples, which on Earth include water-worked current ripples, but on Mars instead form by wind because of the higher kinematic viscosity of the low-density atmosphere. A reevaluation of the wind-deposited strata in the Burns formation (about 3.7 billion years old or younger) identifies potential wind-drag ripple stratification formed under a thin atmosphere. PMID- 27365445 TI - A maleness gene in the malaria mosquito Anopheles gambiae. AB - The molecular pathways controlling gender are highly variable and have been identified in only a few nonmammalian model species. In many insects, maleness is conferred by a Y chromosome-linked M factor of unknown nature. We have isolated and characterized a gene, Yob, for the M factor in the malaria mosquito Anopheles gambiae Yob, activated at the beginning of zygotic transcription and expressed throughout a male's life, controls male-specific splicing of the doublesex gene. Silencing embryonic Yob expression is male-lethal, whereas ectopic embryonic delivery of Yob transcripts yields male-only broods. This female-killing property may be an invaluable tool for creation of conditional male-only transgenic Anopheles strains for malaria control programs. PMID- 27365446 TI - Sex-specific responses to climate change in plants alter population sex ratio and performance. AB - Males and females are ecologically distinct in many species, but whether responses to climate change are sex-specific is unknown. We document sex-specific responses to climate change in the plant Valeriana edulis (valerian) over four decades and across its 1800-meter elevation range. Increased elevation was associated with increased water availability and female frequency, likely owing to sex-specific water use efficiency and survival. Recent aridification caused male frequency to move upslope at 175 meters per decade, a rate of trait shift outpacing reported species' range shifts by an order of magnitude. This increase in male frequency reduced pollen limitation and increased seedset. Coupled with previous studies reporting sex-specific arthropod communities, these results underscore the importance of ecological differences between the sexes in mediating biological responses to climate change. PMID- 27365447 TI - Mycorrhizal association as a primary control of the CO2 fertilization effect. AB - Plants buffer increasing atmospheric carbon dioxide (CO2) concentrations through enhanced growth, but the question whether nitrogen availability constrains the magnitude of this ecosystem service remains unresolved. Synthesizing experiments from around the world, we show that CO2 fertilization is best explained by a simple interaction between nitrogen availability and mycorrhizal association. Plant species that associate with ectomycorrhizal fungi show a strong biomass increase (30 +/- 3%, P < 0.001) in response to elevated CO2 regardless of nitrogen availability, whereas low nitrogen availability limits CO2 fertilization (0 +/- 5%, P = 0.946) in plants that associate with arbuscular mycorrhizal fungi. The incorporation of mycorrhizae in global carbon cycle models is feasible, and crucial if we are to accurately project ecosystem responses and feedbacks to climate change. PMID- 27365448 TI - Frigate birds track atmospheric conditions over months-long transoceanic flights. AB - Understanding how animals respond to atmospheric conditions across space is critical for understanding the evolution of flight strategies and long-distance migrations. We studied the three-dimensional movements and energetics of great frigate birds (Fregata minor) and showed that they can stay aloft for months during transoceanic flights. To do this, birds track the edge of the doldrums to take advantage of favorable winds and strong convection. Locally, they use a roller-coaster flight, relying on thermals and wind to soar within a 50- to 600 meter altitude band under cumulus clouds and then glide over kilometers at low energy costs. To deal with the local scarcity of clouds and gain longer gliding distances, birds regularly soar inside cumulus clouds to use their strong updraft, and they can reach altitudes of 4000 meters, where freezing conditions occur. PMID- 27365449 TI - Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. AB - Analysis of the pattern of proteins or messengerRNAs (mRNAs) in histological tissue sections is a cornerstone in biomedical research and diagnostics. This typically involves the visualization of a few proteins or expressed genes at a time. We have devised a strategy, which we call "spatial transcriptomics," that allows visualization and quantitative analysis of the transcriptome with spatial resolution in individual tissue sections. By positioning histological sections on arrayed reverse transcription primers with unique positional barcodes, we demonstrate high-quality RNA-sequencing data with maintained two-dimensional positional information from the mouse brain and human breast cancer. Spatial transcriptomics provides quantitative gene expression data and visualization of the distribution of mRNAs within tissue sections and enables novel types of bioinformatics analyses, valuable in research and diagnostics. PMID- 27365451 TI - The measure of success. PMID- 27365450 TI - Elucidation of AMPA receptor-stargazin complexes by cryo-electron microscopy. AB - AMPA-subtype ionotropic glutamate receptors (AMPARs) mediate fast excitatory neurotransmission and contribute to high cognitive processes such as learning and memory. In the brain, AMPAR trafficking, gating, and pharmacology is tightly controlled by transmembrane AMPAR regulatory proteins (TARPs). Here, we used cryo electron microscopy to elucidate the structural basis of AMPAR regulation by one of these auxiliary proteins, TARP gamma2, or stargazin (STZ). Our structures illuminate the variable interaction stoichiometry of the AMPAR-TARP complex, with one or two TARP molecules binding one tetrameric AMPAR. Analysis of the AMPAR-STZ binding interfaces suggests that electrostatic interactions between the extracellular domains of AMPAR and STZ play an important role in modulating AMPAR function through contact surfaces that are conserved across AMPARs and TARPs. We propose a model explaining how TARPs stabilize the activated state of AMPARs and how the interactions between AMPARs and their auxiliary proteins control fast excitatory synaptic transmission. PMID- 27365453 TI - In vivo aspects of protein folding and quality control. AB - Most proteins must fold into unique three-dimensional structures to perform their biological functions. In the crowded cellular environment, newly synthesized proteins are at risk of misfolding and forming toxic aggregate species. To ensure efficient folding, different classes of molecular chaperones receive the nascent protein chain emerging from the ribosome and guide it along a productive folding pathway. Because proteins are structurally dynamic, constant surveillance of the proteome by an integrated network of chaperones and protein degradation machineries is required to maintain protein homeostasis (proteostasis). The capacity of this proteostasis network declines during aging, facilitating neurodegeneration and other chronic diseases associated with protein aggregation. Understanding the proteostasis network holds the promise of identifying targets for pharmacological intervention in these pathologies. PMID- 27365452 TI - Immune modulation by MANF promotes tissue repair and regenerative success in the retina. AB - Regenerative therapies are limited by unfavorable environments in aging and diseased tissues. A promising strategy to improve success is to balance inflammatory and anti-inflammatory signals and enhance endogenous tissue repair mechanisms. Here, we identified a conserved immune modulatory mechanism that governs the interaction between damaged retinal cells and immune cells to promote tissue repair. In damaged retina of flies and mice, platelet-derived growth factor (PDGF)-like signaling induced mesencephalic astrocyte-derived neurotrophic factor (MANF) in innate immune cells. MANF promoted alternative activation of innate immune cells, enhanced neuroprotection and tissue repair, and improved the success of photoreceptor replacement therapies. Thus, immune modulation is required during tissue repair and regeneration. This approach may improve the efficacy of stem-cell-based regenerative therapies. PMID- 27365454 TI - Heart failure-potential new targets for therapy. AB - INTRODUCTION/BACKGROUND: Heart failure is a major cause of cardiovascular morbidity and mortality. This review covers current heart failure treatment guidelines, emerging therapies that are undergoing clinical trial, and potential new therapeutic targets arising from basic science advances. SOURCES OF DATA: A non-systematic search of MEDLINE was carried out. International guidelines and relevant reviews were searched for additional articles. AREAS OF AGREEMENT: Angiotensin-converting enzyme inhibitors and beta-blockers are first line treatments for chronic heart failure with reduced left ventricular function. AREAS OF CONTROVERSY: Treatment strategies to improve mortality in heart failure with preserved left ventricular function are unclear. GROWING POINTS: Many novel therapies are being tested for clinical efficacy in heart failure, including those that target natriuretic peptides and myosin activators. A large number of completely novel targets are also emerging from laboratory-based research. Better understanding of pathophysiological mechanisms driving heart failure in different settings (e.g. hypertension, post-myocardial infarction, metabolic dysfunction) may allow for targeted therapies. AREAS TIMELY FOR DEVELOPING RESEARCH: Therapeutic targets directed towards modifying the extracellular environment, angiogenesis, cell viability, contractile function and microRNA-based therapies. PMID- 27365455 TI - The effectiveness of home hand exercise programmes in rheumatoid arthritis: a systematic review. AB - INTRODUCTION: Rheumatoid arthritis (RA) commonly reduces hand function. We systematically reviewed trials to investigate effects of home hand exercise programmes on hand symptoms and function in RA. SOURCES OF DATA: We searched: Medline (1946-), AMED, CINAHL, Physiotherapy Evidence Database, OT Seeker, the Cochrane Library, ISI Web of Science from inception to January 2016. AREAS OF AGREEMENT: Nineteen trials were evaluated. Only three were randomized controlled trials with a low risk of bias (n = 665). Significant short-term improvements occurred in hand function, pain and grip strength, with long-term improvements in hand and upper limb function and pinch strength. AREAS OF CONTROVERSY: Heterogeneity of outcome measures meant meta-analysis was not possible. GROWING POINTS: Evaluation of low and moderate risk of bias trials indicated high intensity home hand exercise programmes led to better short-term outcomes than low-intensity programmes. Such programmes are cost-effective. AREAS TIMELY FOR DEVELOPING RESEARCH: Further research is required to evaluate methods of helping people with RA maintain long-term home hand exercise. PMID- 27365457 TI - Old and new faces of neutropenia in children. PMID- 27365458 TI - Patient-centered research and practice in the era of genomics: a novel approach. PMID- 27365459 TI - The immune microenvironment in Hodgkin lymphoma: T cells, B cells, and immune checkpoints. AB - Classical Hodgkin lymphoma is curable in the majority of cases with chemotherapy and/or radiation. However, 15-20% of patients ultimately relapse and succumb to their disease. Pathologically, classical Hodgkin lymphoma is characterized by rare tumor-initiating Reed-Sternberg cells surrounded by a dense immune microenvironment. However, the role of the immune microenvironment, particularly T and B cells, in either promoting or restricting Classical Hodgkin lymphoma growth remains undefined. Recent dramatic clinical responses seen using monoclonal antibodies against PD-1, a cell surface receptor whose primary function is to restrict T cell activation, have reignited questions regarding the function of the adaptive immune system in classical Hodgkin lymphoma. This review summarizes what is known regarding T cells, B cells, and immune checkpoints in classical Hodgkin lymphoma. PMID- 27365460 TI - Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL 6) guidelines. AB - Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence based recommendations for diagnosis, prevention, prophylaxis and therapy of post transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virus specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged. PMID- 27365462 TI - Debate is healthy: more data are needed. PMID- 27365463 TI - Cementless total knee arthroplasty: current concepts review. AB - As the number of younger and more active patients treated with total knee arthroplasty (TKA) continues to increase, consideration of better fixation as a means of improving implant longevity is required. Cemented TKA remains the reference standard with the largest body of evidence and the longest follow-up to support its use. However, cementless TKA, may offer the opportunity of a more bone-sparing procedure with long lasting biological fixation to the bone. We undertook a review of the literature examining advances of cementless TKA and the reported results. Cite this article: Bone Joint J 2016;98-B:867-73. PMID- 27365464 TI - Management of sports injuries of the foot and ankle: an update. AB - Sporting injuries around the ankle vary from simple sprains that will resolve spontaneously within a few days to severe injuries which may never fully recover and may threaten the career of a professional athlete. Some of these injuries can be easily overlooked altogether or misdiagnosed with potentially devastating effects on future performance. In this review article, we cover some of the common and important sporting injuries involving the ankle including updates on their management and outcomes. Cite this article: Bone Joint J 2016;98-B:874-83. PMID- 27365461 TI - Whole exome sequencing in families at high risk for Hodgkin lymphoma: identification of a predisposing mutation in the KDR gene. AB - Hodgkin lymphoma shows strong familial aggregation but no major susceptibility genes have been identified to date. The goal of this study was to identify high penetrance variants using whole exome sequencing in 17 Hodgkin lymphoma prone families with three or more affected cases or obligate carriers (69 individuals), followed by targeted sequencing in an additional 48 smaller HL families (80 individuals). Alignment and variant calling were performed using standard methods. Dominantly segregating, rare, coding or potentially functional variants were further prioritized based on predicted deleteriousness, conservation, and potential importance in lymphoid malignancy pathways. We selected 23 genes for targeted sequencing. Only the p.A1065T variant in KDR (kinase insert domain receptor) also known as VEGFR2 (vascular endothelial growth factor receptor 2) was replicated in two independent Hodgkin lymphoma families. KDR is a type III receptor tyrosine kinase, the main mediator of vascular endothelial growth factor induced proliferation, survival, and migration. Its activity is associated with several diseases including lymphoma. Functional experiments have shown that p.A1065T, located in the activation loop, can promote constitutive autophosphorylation on tyrosine in the absence of vascular endothelial growth factor and that the kinase activity was abrogated after exposure to kinase inhibitors. A few other promising mutations were identified but appear to be "private". In conclusion, in the largest sequenced cohort of Hodgkin lymphoma families to date, we identified a causal mutation in the KDR gene. While independent validation is needed, this mutation may increase downstream tumor cell proliferation activity and might be a candidate for targeted therapy. PMID- 27365465 TI - A unified theory of bone healing and nonunion: BHN theory. AB - This article presents a unified clinical theory that links established facts about the physiology of bone and homeostasis, with those involved in the healing of fractures and the development of nonunion. The key to this theory is the concept that the tissue that forms in and around a fracture should be considered a specific functional entity. This 'bone-healing unit' produces a physiological response to its biological and mechanical environment, which leads to the normal healing of bone. This tissue responds to mechanical forces and functions according to Wolff's law, Perren's strain theory and Frost's concept of the "mechanostat". In response to the local mechanical environment, the bone-healing unit normally changes with time, producing different tissues that can tolerate various levels of strain. The normal result is the formation of bone that bridges the fracture - healing by callus. Nonunion occurs when the bone-healing unit fails either due to mechanical or biological problems or a combination of both. In clinical practice, the majority of nonunions are due to mechanical problems with instability, resulting in too much strain at the fracture site. In most nonunions, there is an intact bone-healing unit. We suggest that this maintains its biological potential to heal, but fails to function due to the mechanical conditions. The theory predicts the healing pattern of multifragmentary fractures and the observed morphological characteristics of different nonunions. It suggests that the majority of nonunions will heal if the correct mechanical environment is produced by surgery, without the need for biological adjuncts such as autologous bone graft. Cite this article: Bone Joint J 2016;98-B:884-91. PMID- 27365466 TI - The manufacture of generic replicas of implants for arthroplasty of the hip and knee: is it regulated and will it save money? AB - Joint replacement of the hip and knee remain very satisfactory operations. They are, however, expensive. The actual manufacturing of the implant represents only 30% of the final cost, while sales and marketing represent 40%. Recently, the patents on many well established and successful implants have expired. Companies have started producing and distributing implants that purport to replicate existing implants with good long-term results. The aims of this paper are to assess the legality, the monitoring and cost saving implications of such generic implants. We also assess how this might affect the traditional orthopaedic implant companies. Cite this article: Bone Joint J 2016;98-B:892-900. PMID- 27365467 TI - Hip resurfacing for osteonecrosis: two- to 18-year results of the Conserve Plus design and technique. AB - AIMS: Hip resurfacing arthroplasty (HRA) is an alternative to conventional total hip arthroplasty for patients with osteonecrosis (ON) of the femoral head. Our aim was to report the long-term outcome of HRA, which is not currently known. PATIENTS AND METHODS: Long-term survivorship, clinical scores and radiographic results for 82 patients (99 hips) treated with HRA for ON over a period of 18 years were reviewed retrospectively. The mean age of the 67 men and 15 women at the time of surgery was 40.8 years (14 to 64). Patients were resurfaced regardless of the size of the osteonecrotic lesion. RESULTS: The mean clinical follow-up was 10.8 years (2 to 18). The mean University of California, Los Angeles hip scores at the last follow-up were 9.3, 9.4, 9.2 and 6.8 for pain, walking, function and activity, respectively. A total of six hips underwent revision surgery, four for loosening of the femoral component and two for loosening of the acetabular component. Using any revision as an end point, the 15 year Kaplan-Meier survivorship was 90.3%. There were no wear-related failures. There were no femoral failures among the hips reconstructed with a cemented metaphyseal stem. A total of five hips showed narrowing of the femoral neck; all stabilised and remain asymptomatic, 21 showed signs of femoral neck impingement. CONCLUSION: To our knowledge, this is the first report of a series of HRA performed for ON with 15-year survivorship. Our data confirm that patients with advanced stages of ON of the femoral head are excellent candidates for HRA. Cite this article: Bone Joint J 2016;98-B:901-9. PMID- 27365468 TI - Functional orientation of the acetabular component in ceramic-on-ceramic total hip arthroplasty and its relevance to squeaking. AB - AIMS: Long-term clinical outcomes for ceramic-on-ceramic (CoC) bearings are encouraging. However, there is a risk of squeaking. Guidelines for the orientation of the acetabular component are defined from static imaging, but the position of the pelvis and thus the acetabular component during activities associated with edge-loading are likely to be very different from those measured when the patient is supine. We assessed the functional orientation of the acetabular component. PATIENTS AND METHODS: A total of 18 patients with reproducible squeaking in their CoC hips during deep flexion were investigated with a control group of 36 non-squeaking CoC hips. The two groups were matched for the type of implant, the orientation of the acetabular component when supine, the size of the femoral head, ligament laxity, maximum hip flexion and body mass index. RESULTS: The mean functional anteversion of the acetabular component at the point when patients initiated rising from a seated position was significantly less in the squeaking group than in the control group, 8.1 degrees (-10.5 degrees to 36.0 degrees ) and 21.1 degrees (-1.9 degrees to 38.4 degrees ) respectively (p = 0.002). CONCLUSION: The functional orientation of the acetabular component during activities associated with posterior edge-loading are different from those measured when supine due to patient-specific pelvic kinematics. Individuals with a large anterior pelvic tilt during deep flexion might be more susceptible to posterior edge-loading and squeaking as a consequence of a significant decrease in the functional anteversion of the acetabular component. Cite this article: Bone Joint J 2016;98-B:910-16. PMID- 27365469 TI - The effect of using components from different manufacturers on the rate of wear and corrosion of the head-stem taper junction of metal-on-metal hip arthroplasties. AB - AIMS: Surgeons have commonly used modular femoral heads and stems from different manufacturers, although this is not recommended by orthopaedic companies due to the different manufacturing processes. We compared the rate of corrosion and rate of wear at the trunnion/head taper junction in two groups of retrieved hips; those with mixed manufacturers (MM) and those from the same manufacturer (SM). MATERIALS AND METHODS: We identified 151 retrieved hips with large-diameter cobalt-chromium heads; 51 of two designs that had been paired with stems from different manufacturers (MM) and 100 of seven designs paired with stems from the same manufacturer (SM). We determined the severity of corrosion with the Goldberg corrosion score and the volume of material loss at the head/stem junction. We used multivariable statistical analysis to determine if there was a significant difference between the two groups. RESULTS: We found no significant difference in the corrosion scores of the two groups. The median rate of material loss at the head/stem junction for the MM and SM groups were 0.39 mm(3)/year (0.00 to 4.73) and 0.46 mm(3)/year (0.00 to 6.71) respectively; this difference was not significant after controlling for confounding factors (p = 0.06). CONCLUSION: The use of stems with heads of another manufacturer does not appear to affect the amount of metal lost from the surfaces between these two components at total hip arthroplasty. Other surgical, implant and patient factors should be considered when determining the mechanisms of failure of large diameter metal-on-metal hip arthroplasties. Cite this article: Bone Joint J 2016;98-B:917-24. PMID- 27365470 TI - The clinical implications of metal debris release from the taper junctions and bearing surfaces of metal-on-metal hip arthroplasty: joint fluid and blood metal ion concentrations. AB - AIMS: We wished to investigate the influence of metal debris exposure on the subsequent immune response and resulting soft-tissue injury following metal-on metal (MoM) hip arthroplasty. Some reports have suggested that debris generated from the head-neck taper junction is more destructive than equivalent doses from metal bearing surfaces. PATIENTS AND METHODS: We investigated the influence of the source and volume of metal debris on chromium (Cr) and cobalt (Co) concentrations in corresponding blood and hip synovial fluid samples and the observed agglomerated particle sizes in excised tissues using multiple regression analysis of prospectively collected data. A total of 199 explanted MoM hips (177 patients; 132 hips female) were analysed to determine rates of volumetric wear at the bearing surfaces and taper junctions. RESULTS: The statistical modelling suggested that a greater source contribution of metal debris from the taper junction was associated with smaller aggregated particle sizes in the local tissues and a relative reduction of Cr ion concentrations in the corresponding synovial fluid and blood samples. Metal debris generated from taper junctions appears to be of a different morphology, composition and therefore, potentially, immunogenicity to that generated from bearing surfaces. CONCLUSION: The differences in debris arising from the taper and the articulating surfaces may provide some understanding of the increased incidence of soft-tissue reactions reported in patients implanted with MoM total hip arthroplasties compared with patients with hip resurfacings. Cite this article: Bone Joint J 2016;98-B:925-33. PMID- 27365471 TI - The role for arthroscopic partial meniscectomy in knees with degenerative changes: a systematic review. AB - AIMS: Patients with osteoarthritis of the knee commonly have degenerative meniscal tears. Arthroscopic meniscectomy is frequently performed, although the benefits are debatable. Recent studies have concluded that there is no role for arthroscopic washout in osteoarthritis of the knee. Our aim was to perform a systematic review to assess the evidence for the efficacy of arthroscopic meniscectomy in patients with meniscal tears and degenerative changes in the knee. PATIENTS AND METHODS: A literature search was performed, using the PubMed/MEDLINE database, for relevant articles published between 1975 and 2015. A total of six studies, including five randomised controlled trials and one cross sectional study of a prospective cohort, met the inclusion criteria. Relevant information including study design, operations, the characteristics of the patients, outcomes, adverse events and further operations were extracted. RESULTS: The degree of osteoarthritis in the patients who were included and the rate of cross over from one form of treatment to another varied in the studies. Two randomised controlled trials showed a benefit of arthroscopic surgery in patients with limited degenerative joint disease, compared with conservative treatment. One cross-sectional study showed that patients with less severe degenerative changes had better outcomes. CONCLUSION: Patients with symptomatic meniscal tears and degenerative changes in the knee can benefit from arthroscopic meniscectomy, particularly if the osteoarthritis is mild. A trial of conservative management may be effective and should be considered, especially in patients with moderate osteoarthritis. Cite this article: Bone Joint J 2016;98-B:934-8. PMID- 27365472 TI - No difference in clinical outcome between patient-matched positioning guides and conventional instrumented total knee arthroplasty two years post-operatively: a multicentre, double-blind, randomised controlled trial. AB - AIMS: We wished to compare the clinical outcome, as assessed by questionnaires and the rate of complications, in total knee arthroplasty (TKA) undertaken with patient-matched positioning guides (PMPGs) or conventional instruments. PATIENTS AND METHODS: A total of 180 patients (74 men, 106 women; mean age 67 years) were included in a multicentre, adequately powered, double-blind, randomised controlled trial. The mean follow-up was 44 months (24 to 57). RESULTS: There were no significant or clinically relevant differences between the two groups for all outcome measures (Knee Society Score, p = 0.807; Oxford Knee Score, p = 0.304; Western Ontario and McMaster osteoarthritis index, p = 0.753; visual analogue scale for pain, p = 0.227; EuroQol-5D-3L index score, p = 0.610; EuroQol 5D-3L VAS health, p = 0.968.) There was no difference in the rate of complications (p = 0.291). CONCLUSION: PMPGs are already in relatively common use and their short-term clinical results are equal to conventional instrumented TKA. Cite this article: Bone Joint J 2016;98-B:939-44. PMID- 27365473 TI - Metallic hemiarthroplasty for the treatment of end-stage hallux rigidus: mid-term implant survival, functional outcome and cost analysis. AB - AIMS: To examine the mid-term outcome and cost utility of the BioPro metallic hemiarthroplasty for the treatment of hallux rigidius. PATIENTS AND METHODS: We reviewed 97 consecutive BioPro metallic hemiarthroplasties performed in 80 patients for end-stage hallux rigidus, with a minimum follow-up of five years. There were 19 men and 61 women; their mean age was 55 years (22 to 74). No patient was lost to follow-up. RESULTS: A total of 12 patients (15 first metatarso-phalangeal joints (MTPJs)) required a revision; one for infection, two for osteolysis and 12 for pain. The all cause rate of survival at five years was 85.6% (95% confidence interval (CI) 83.5 to 87.9). Younger age was a significant predictor of revision (odds ratio 1.09, 95% CI 1.02 to 1.17, p = 0.014) on excluding infection and adjusting for confounding variables (Cox regression). Significant improvements were demonstrated at five years in the Manchester Oxford Foot Questionnaire (13.9, 95% CI 10.5 to 17.2) and in the physical component of the Short Form-12 score (6.5, 95% CI 4.1 to 8.9). The overall rate of satisfaction was 75%. The cost per quality adjusted life year at five years, accounting for a 14% rate of revision was between L4431 and L6361 depending on the complexity and morbidity of the patient. CONCLUSION: The BioPro hemiarthroplasty offers good short to mid-term functional outcome and is a cost effective intervention. The relatively high revision rate is associated with younger age and perhaps the use of this implant should be limited to older patients. Cite this article: Bone Joint J 2016;98-B:945-51. PMID- 27365474 TI - The Osseointegration Group of Australia Accelerated Protocol (OGAAP-1) for two stage osseointegrated reconstruction of amputated limbs. AB - AIMS: This study describes the Osseointegration Group of Australia's Accelerated Protocol two-stage strategy (OGAAP-1) for the osseointegrated reconstruction of amputated limbs. PATIENTS AND METHODS: We report clinical outcomes in 50 unilateral trans-femoral amputees with a mean age of 49.4 years (24 to 73), with a minimum one-year follow-up. Outcome measures included the Questionnaire for persons with a Trans-Femoral Amputation, the health assessment questionnaire Short-Form-36 Health Survey, the Amputation Mobility Predictor scores presented as K-levels, 6 Minute Walk Test and timed up and go tests. Adverse events included soft-tissue problems, infection, fractures and failure of the implant. RESULTS: Our results demonstrated statistically significant improvements in all five outcome measures. A total of 27 patients experienced adverse events but at the conclusion of the study, all 50 were walking on osseointegrated prostheses. CONCLUSION: These results demonstrate that osseointegrated prostheses are a suitable alternative to socket-fit devices for amputees experiencing socket related discomfort and that our strategy offers more rapid progress to walking than other similar protocols. Cite this article: Bone Joint J 2016;98-B:952-60. PMID- 27365475 TI - Effects of depression and inflammatory factors on chronic conditions of the wrist. AB - AIMS: Chronic conditions of the wrist may be difficult to manage because pain and psychiatric conditions are correlated with abnormal function of the hand. Additionally, intra-articular inflammatory cytokines may cause pain. We aimed to validate the measurement of inflammatory cytokines in these conditions and identify features associated with symptoms. PATIENTS AND METHODS: The study included 38 patients (18 men, 20 women, mean age 43 years) with a chronic condition of the wrist who underwent arthroscopy. Before surgery, the Self-Rating Depression Scale (SDS), Hand20 questionnaire and a visual analogue scale (VAS) for pain were used. Cytokine and chemokine levels in the synovial fluid of the wrist were measured using enzyme-linked immunosorbent assays and correlations between the levels with pain were analysed. Gene expression profiles of the synovial membranes were assessed using quantitative polymerase chain reaction. RESULTS: Older patients had high pre-operative Hand20 scores. One-year post operative Hand20 and VAS scores and pre-operative VAS scores correlated with SDS scores. Post-operative VAS scores negatively correlated with the expression of nerve growth factor and SDS scores positively correlated with the expression of tumour necrosis factor-alpha and negatively correlated with the expression of tumour necrosis factor-converting enzyme. CONCLUSION: There was a positive correlation between depression and chronic conditions of the wrist. Levels of some cytokines correlate with pain and depression. Additionally, cytokines may be important in the assessment and treatment of chronic conditions of the wrist and depression. Cite this article: Bone Joint J 2016;98-B:961-8. PMID- 27365476 TI - Reverse total shoulder arthroplasty using a trabecular metal glenoid base plate: functional and radiological outcomes at two to five years. AB - AIM: We present the medium-term clinical results of a reverse total shoulder arthroplasty with a trabecular metal glenoid base plate. PATIENTS AND METHODS: We reviewed 125 consecutive primary reverse total shoulder arthroplasties (RTSA) implanted in 124 patients for rotator cuff arthropathy. There were 100 women and 24 men in the study group with a mean age of 76 years (58 to 89). The mean follow up was 32 months (24 to 60). No patient was lost to follow-up. RESULTS: There were statistically significant improvements in the mean range of movement and Oxford Shoulder Score (p < 0.001). Kaplan-Meier survivorship at five years was 96.7% (95% confidence interval 91.5 to 98.7) with aseptic glenoid failure as the end point. Radiologically, 63 shoulders (50.4%) showed no evidence of notching, 51 (40.8%) had grade 1 notching, ten (8.0%) had grade 2 notching and one (0.8%) had grade 4 notching. Radiolucency around the glenoid base plate was found in one patient (0.8%) and around the humeral stem in five (4.0%). In all, three RTSA (2.4%) underwent revision surgery for aseptic mechanical failure of the glenoid within 11 months of surgery due to malseating of the glenosphere. CONCLUSION: The clinical results of this large independent single unit series are comparable to those from previous series of RTSA reported in the literature. A trabecular metal base plate is safe and effective in the medium-term. Cite this article: Bone Joint J 2016;98-B:969-75. PMID- 27365477 TI - Infection in total elbow arthroplasty with stable components: outcomes of a staged surgical protocol with retention of the components. AB - AIMS: We describe the use of a protocol of irrigation and debridement (I&D) with retention of the implant for the treatment of periprosthetic infection of a total elbow arthroplasty (TEA). This may be an attractive alternative to staged re implantation. PATIENTS AND METHODS: Between 1990 and 2010, 23 consecutive patients were treated in this way. Three were lost to follow-up leaving 20 patients (21 TEAs) in the study. There were six men and 14 women. Their mean age was 58 years (23 to 76). The protocol involved: component unlinking, irrigation and debridement (I&D), and the introduction of antibiotic laden cement beads; organism-specific intravenous antibiotics; repeat I&D and re-linkage of the implant if appropriate; long-term oral antibiotic therapy. RESULTS: The mean follow-up was 7.1 years (2 to 16). The infecting micro-organisms were Staphylococcus aureus in nine, coagulase-negative Staphylococcus in 13, Corynebacterium in three and other in six cases. Re-operations included three repeat staged I&Ds, two repeat superficial I&Ds and one fasciocutaneous forearm flap. One patient required removal of the implant due to persistent infection. All except three patients rated their pain as absent or mild. Outcome was rated as good or excellent in 15 patients (mean Mayo Elbow Performance Score 78 points, (5 to 100) with a mean flexion-extension arc of 103 degrees (40 degrees to 150 degrees )). CONCLUSION: A staged protocol can be successful in retaining stable components of an infected TEA. Function of the elbow may compare unfavourably to that after an uncomplicated TEA. Cite this article: Bone Joint J 2016;98-B:976 83. PMID- 27365478 TI - Wound drains in non-complex lumbar surgery: a systematic review. AB - AIMS: Our aim was to perform a systematic review of the literature to assess the incidence of post-operative epidural haematomas and wound infections after one-, or two-level, non-complex, lumbar surgery for degenerative disease in patients with, or without post-operative wound drainage. PATIENTS AND METHODS: Studies were identified from PubMed and EMBASE, up to and including 27 August 2015, for papers describing one- or two-level lumbar discectomy and/or laminectomy for degenerative disease in adults which reported any form of subcutaneous or subfascial drainage. RESULTS: Eight papers describing 1333 patients were included. Clinically relevant post-operative epidural haematomas occurred in two (0.15%), and wound infections in ten (0.75%) patients. Epidural haematomas occurred in two (0.47%) patients who had wound drainage (n = 423) and in none of those without wound drainage (n = 910). Wound infections occurred in two (0.47%) patients with wound drainage and in eight (0.88%) patients without wound drainage. CONCLUSION: These data suggest that the routine use of a wound drain in non-complex lumbar surgery does not prevent post-operative epidural haematomas and that the absence of a drain does not lead to a significant change in the incidence of wound infection. Cite this article: Bone Joint J 2016;98-B:984-9. PMID- 27365479 TI - Correlations and time-dependent changes of upper arm performance tests, the Japanese Orthopaedic Association score, and a newly developed patient-based outcome measure : the Japanese Orthopaedic Cervical Myelopathy Questionnaire. AB - AIMS: In this prospective observational study, we investigated the time-dependent changes and correlations of upper arm performance tests (ten-second test and Simple Test for Evaluating Hand Function (STEF), the Japanese Orthopaedic Association (JOA) score, and the JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) in 31 patients with cervical myelopathy who had undergone surgery. PATIENTS AND METHODS: We hypothesised that all the indices correlate with each other, but show slightly different recovery patterns, and that the newly described JOACMEQ is a sensitive outcome measure. RESULTS: Peak recoveries were achieved one month post-operatively in the ten-second test and JOACMEQ upper extremity function (UEF) subscale, and at three months in the JOA and STEF scores. The recoveries of all indices were maintained until six months post operatively. The upper extremity function (UEF) subscale in the JOACMEQ showed the strongest correlation with STEF although all the indices correlated with each other. Patients with >= 20 and < 20 acquired points in the UEF subscale were classified into the UEF-improved and UEF-unimproved groups. Comparisons between the groups showed that pre-operative evaluation of "coordinated motion" of the STEF was significantly low in the UEF-unimproved group. CONCLUSION: These results indicate that the JOACMEQ is a concise, sensitive, patient-based outcome measure for evaluating functional recovery in patients with cervical myelopathy who have undergone surgery. Cite this article: Bone Joint J 2016;98-B:990-6. PMID- 27365480 TI - Maintenance of spontaneous lumbar curve correction following thoracic fusion of main thoracic curves in adolescent idiopathic scoliosis. AB - AIMS: The aims of our study were to provide long-term information on the behaviour of the thoracolumbar/lumbar (TL/L) curve after thoracic anterior correction and fusion (ASF) and to determine the impact of ASF on pulmonary function. PATIENTS AND METHODS: A total of 41 patients (four males, 37 females) with main thoracic (MT) adolescent idiopathic scoliosis (AIS) treated with ASF were included. Mean age at surgery was 15.2 years (11 to 27). Mean follow-up period was 13.5 years (10 to 18). RESULTS: For the TL/L curve, the mean curve flexibility evaluated with supine pre-operative bending radiographs was 78.6% (standard deviation 16.5%), with no significant loss of correction observed. On comparing patients with an increase of the TL/L curve increase (> 4o, n = 9, 22%) to those without, significant differences were observed in the correction rate of the MT curve at the final follow-up (p = 0.011), correction loss of the MT curve (p = 0.003) and the proportion of patients who had semi-rigid instrumentation (p = 0.003). Pre-operative percentage predicted forced vital capacity (%FVC) was 80%, dropping to 72% at final follow-up (p < 0.001). The Scoliosis Research Society questionnaire score was not significantly different between patients with and without a TL/L curve increase (p = 0.606). Spontaneous lumbar curve correction (SLCC) was maintained up to 18 years following selective ASF in most patients and demonstrated significant correlation with maintenance of MT curve correction. CONCLUSION: Maintenance of MT curve correction using rigid instrumentation provided stable SLCC over time. An observed 8% decrease in %FVC indicates that ASF should be reserved for patients with no or only mild pulmonary impairment. Cite this article: Bone Joint J 2016;98-B:997-1002. PMID- 27365481 TI - The patterns of injury and management of cuboid fractures: a retrospective case series. AB - AIMS: Although infrequent, a fracture of the cuboid can lead to significant disruption of the integrity of the midfoot and its function. The purpose of this study was to classify the pattern of fractures of the cuboid, relate them to the mechanism of injury and suggest methods of managing them. PATIENTS AND METHODS: We performed a retrospective review of patients with radiologically reported cuboid fractures. Fractures were grouped according to commonly occurring patterns of injury. A total of 192 fractures in 188 patients were included. They were classified into five patterns of injury. RESULTS: Type 1 fractures (93 fractures, 48.4%) are simple avulsion injuries involving the capsule of the calcaneo-cuboid joint. Type 2 fractures (25 fractures, 13%) are isolated extra-articular injuries involving the body of the cuboid. Type 3 injuries (13 factures, 6.8%) are intra articular fractures solely within the body of the cuboid. Type 4 fractures (35 fractures, 18.2%) are associated with disruption of the midfoot and tarsometatarsal injuries. Type 5 fractures (26 fractures, 13.5%) occur in conjunction with disruption of the mid-tarsal joint and either crushing of the lateral column alone or of both medial and lateral columns. Fractures with significant articular disruption or with loss of length of the lateral column underwent fixation. This involved either internal fixation to restore the anatomy of the cuboid and/or restoration of the length of the columns with bridging constructs using internal or external fixation. CONCLUSION: A classification system for fractures of the cuboid is proposed in relation to the mechanism of injury. The treatment of these fractures is described. Cite this article: Bone Joint J 2016;98-B:1003-8. PMID- 27365482 TI - Children under 5 dying from preventable diseases, says UN. PMID- 27365483 TI - Global helium crisis deflates after discovery of African reserve. PMID- 27365484 TI - Mesenchymal Stem Cell Spheroids Retain Osteogenic Phenotype Through alpha2beta1 Signaling. AB - : The induction of mesenchymal stem cells (MSCs) toward the osteoblastic lineage using osteogenic supplements prior to implantation is one approach under examination to enhance their bone-forming potential. MSCs rapidly lose their induced phenotype upon removal of the soluble stimuli; however, their bone forming potential can be sustained when provided with continued instruction via extracellular matrix (ECM) cues. In comparison with dissociated cells, MSC spheroids exhibit improved survival and secretion of trophic factors while maintaining their osteogenic potential. We hypothesized that entrapment of MSC spheroids formed from osteogenically induced cells would exhibit better preservation of their bone-forming potential than would dissociated cells from monolayer culture. Spheroids exhibited comparable osteogenic potential and increased proangiogenic potential with or without osteogenic preconditioning versus monolayer-cultured MSCs. Spheroids were then entrapped in collagen hydrogels, and the osteogenic stimulus was removed. In comparison with entrapped dissociated MSCs, spheroids exhibited significantly increased markers of osteogenic differentiation. The capacity of MSC spheroids to retain their osteogenic phenotype upon withdrawal of inductive cues was mediated by alpha2beta1 integrin binding to cell-secreted ECM. These results demonstrate the capacity of spheroidal culture to sustain the mineral-producing phenotype of MSCs, thus enhancing their contribution toward bone formation and repair. SIGNIFICANCE: Despite the promise of mesenchymal stem cells (MSCs) for cell-based therapies for tissue repair and regeneration, there is little evidence that transplanted MSCs directly contribute to new bone formation, suggesting that induced cells rapidly lose their osteogenic phenotype or undergo apoptosis. In comparison with dissociated cells, MSC spheroids exhibit increased trophic factor secretion and improved cell survival. The loss of phenotype represents a significant clinical challenge for cell therapies, yet there is no evidence for whether MSC spheroids retain their osteogenic phenotype upon entrapment in a clinically relevant biomaterial. These findings demonstrate that MSC spheroids retain their osteogenic phenotype better than do dissociated MSCs, and this is due to integrin engagement with the cell-secreted extracellular matrix. These data provide evidence for a novel approach for potentiating the use of MSCs in bone repair. PMID- 27365485 TI - Preischemic Administration of Nonexpanded Adipose Stromal Vascular Fraction Attenuates Acute Renal Ischemia/Reperfusion Injury and Fibrosis. AB - : Ischemia/reperfusion (IR)-induced acute kidney injury (AKI) is a common clinical syndrome. Stem/progenitor cell therapy is a promising option to foster the intrinsic capacity for kidney regeneration. However, there are still several challenges to be resolved, including the potential risks during cell culture, low retention rate after transplantation, and unclear effect on the progression of chronic kidney disease (CKD). Recently, nonexpanded adipose stromal vascular fraction (SVF) has been regarded as an attractive cell source for cell-based therapy. Preconditioning with ischemia has been suggested as a useful method to promote the retention and survival of transplanted cells in vivo. In this study, freshly isolated autologous SVF was transplanted to the kidney of rats before ischemia, and then an IR-induced AKI model was established. Postischemic administration of SVF to the kidney was performed after renal IR injury was induced. A higher cell retention rate was detected in the preischemic group. Preischemic administration of SVF showed stronger functional and morphologic protection from renal IR injury than postischemic administration, through enhancing tubular cell proliferation and reducing apoptosis. Progression of kidney fibrosis was also significantly delayed by preischemic administration of SVF, which exhibited stronger inhibition of transforming growth factor-beta1 induced epithelia-mesenchymal transition and microvascular rarefaction. In addition, in vitro study showed that prehypoxic administration of SVF could significantly promote the proliferation, migration, and survival of hypoxic renal tubular epithelial cells. In conclusion, our study demonstrated that preischemic administration of nonexpanded adipose SVF protected the kidney from both acute IR injury and long-term risk of developing CKD. SIGNIFICANCE: Renal ischemia/reperfusion (IR) injury is a common clinical syndrome. Cell-based therapy provides a promising option to promote renal repair after IR injury. However, several challenges still remain because of the potential risks during cell culture, low retention rate after transplantation, and unclear effect on the progression of chronic kidney disease. Stromal vascular fraction (SVF) is considered as an attractive cell source. This study demonstrated that preischemic administration of uncultured SVF could increase cell retention and then improve renal function and structure at both early and long-term stage after IR, which may provide a novel therapeutic approach for IR injury. PMID- 27365486 TI - Effect of Function-Enhanced Mesenchymal Stem Cells Infected With Decorin Expressing Adenovirus on Hepatic Fibrosis. AB - : Bone marrow-derived mesenchymal stem cells (BM-MSCs) are known to have an antifibrotic effect and could be used as vehicles for targeted gene delivery. Decorin plays a protective role against fibrogenesis by modulating the degradation of the extracellular matrix. The aim of this study was to determine whether the antifibrotic effect of a combination treatment consisting of BM-MSCs and decorin on hepatic fibrosis is superior to BM-MSCs alone. The effects of BM MSCs infected with decorin-expressing adenovirus (DCN-MSCs) on hepatic fibrosis were examined in a rat model of thioacetamide (TAA)-induced cirrhosis. The effects of infection with decorin-expressing adenovirus and of incubation with the conditioned medium of DCN-MSCs on transforming growth factor-beta (TGF-beta) signaling were analyzed in immortalized human hepatic stellate cells (HSCs). According to the Laennec fibrosis scoring system, cirrhotic livers from rats treated with DCN-MSCs exhibited histological improvement compared with cirrhotic livers from rats treated with control adenovirus-infected MSCs (CA-MSCs). DCN-MSC treatment reduced hepatic collagen distribution, lowered the hydroxyproline content, and rescued liver function impairment in rats with TAA-induced cirrhosis. These protective effects were more potent with DCN-MSCs than with CA MSCs. The upregulation of collagen-1, alpha-smooth muscle actin (alpha-SMA), TGF beta1, and Smad3 phosphorylation in cirrhotic livers was prevented by DCN-MSC administration. Intriguingly, medium from cultured DCN-MSCs blocked both Smad3 phosphorylation and exogenous TGF-beta1 stimulated alpha-SMA synthesis in HSCs. DCN-MSCs exert strong protective effects against hepatic fibrosis by suppressing TGF-beta/Smad signaling. Thus, treatment with DCN-MSCs is a potentially novel and efficient therapeutic approach for patients with intractable cirrhosis. SIGNIFICANCE: A combination treatment consisting of bone marrow-derived mesenchymal stem cells (BM-MSCs) and decorin strongly inhibited the progression of thioacetamide-induced hepatic fibrosis in rats, compared with BM-MSCs alone. Furthermore, the significant inhibitory effect of BM-MSCs infected with decorin expressing adenovirus was attributed to suppressing transforming growth factor beta (TGF-beta)/Smad signaling pathway, supported by attenuation of TGF-beta1 expression and inhibition of Smad3 phosphorylation. Therefore, treatment with BM MSCs infected with decorin-expressing adenovirus could constitute a novel and efficient therapeutic approach for patients with intractable cirrhosis. PMID- 27365487 TI - Allogeneic Mesenchymal Stem Cell Therapy Promotes Osteoblastogenesis and Prevents Glucocorticoid-Induced Osteoporosis. AB - : Gene-modified mesenchymal stem cell (MSC)-like cells with enhanced bone marrow homing and osteogenesis have been used in treating glucocorticoid-induced murine osteoporosis (GIOP). Recent preclinical studies have further demonstrated the immunomodulatory and anticatabolic potential of allogeneic MSCs in treating osteoporosis under inflammatory and autoimmune conditions. In this study, we investigated whether systemic infusion of allogeneic MSCs without genetic manipulation could prevent GIOP, whether anabolic and anticatabolic effects existed, and whether homing or immunomodulation underlay the putative therapeutic effects. Allogeneic bone marrow-derived MSCs (BMMSCs) were isolated, identified, and systemically infused into mice treated with excessive dexamethasone. We revealed that allogeneic MSC transplantation prevented the reduction of bone mass and strength in GIOP. Bone histomorphometric analyses of bone remodeling demonstrated the maintenance of bone formation and osteoblast survival after MSC therapy. Using green fluorescent protein (GFP)-labeled BMMSCs, we showed that donor BMMSCs(GFP) homed and inhabited recipient bone marrow for at least 4 weeks and prevented recipient bone marrow cell apoptosis, as shown by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Furthermore, donor BMMSCs(GFP) committed to Osterix (Osx)(+) osteoblast progenitors and induced recipient osteoblastogenesis, as exhibited by GFP-Osx double-labeling immunofluorescence analysis. No anticatabolic effects or systemic immunomodulatory effects of infused BMMSCs were detected. These findings demonstrated that allogeneic MSC therapy prevented GIOP by inhabiting and functioning in recipient bone marrow, which promoted osteoblastogenesis, which in turn maintained bone formation. Our findings provide important information regarding cell-based anabolic therapy for GIOP and uncover MSC behaviors following the homing event. SIGNIFICANCE: This study revealed the therapeutic potential of systemically infused, genetically unmodified allogeneic MSCs in glucocorticoid-induced osteoporosis. The donor MSCs inhabited recipient bone marrow and promoted osteoblastogenesis. The therapeutic effects were based on maintenance of bone formation. These results provide important information regarding cell-based anabolic therapy for glucocorticoid-induced osteoporosis and uncover previously unrecognized mesenchymal stem cell behaviors following a homing event. The current study also indicates that minimizing the time of cell culture confers an advantage for increasing transplanted mesenchymal stem cells to the targeted organ to promote therapeutic effects. PMID- 27365488 TI - Clinical and pathogenic features of ETV6-related thrombocytopenia with predisposition to acute lymphoblastic leukemia. AB - ETV6-related thrombocytopenia is an autosomal dominant thrombocytopenia that has been recently identified in a few families and has been suspected to predispose to hematologic malignancies. To gain further information on this disorder, we searched for ETV6 mutations in the 130 families with inherited thrombocytopenia of unknown origin from our cohort of 274 consecutive pedigrees with familial thrombocytopenia. We identified 20 patients with ETV6-related thrombocytopenia from seven pedigrees. They have five different ETV6 variants, including three novel mutations affecting the highly conserved E26 transformation-specific domain. The relative frequency of ETV6-related thrombocytopenia was 2.6% in the whole case series and 4.6% among the families with known forms of inherited thrombocytopenia. The degree of thrombocytopenia and bleeding tendency of the patients with ETV6-related thrombocytopenia were mild, but four subjects developed B-cell acute lymphoblastic leukemia during childhood, resulting in a significantly higher incidence of this condition compared to that in the general population. Clinical and laboratory findings did not identify any particular defects that could lead to the suspicion of this disorder from the routine diagnostic workup. However, at variance with most inherited thrombocytopenias, platelets were not enlarged. In vitro studies revealed that the maturation of the patients' megakaryocytes was defective and that the patients have impaired proplatelet formation. Moreover, platelets from patients with ETV6-related thrombocytopenia have reduced ability to spread on fibrinogen. Since the dominant thrombocytopenias due to mutations in RUNX1 and ANKRD26 are also characterized by normal platelet size and predispose to hematologic malignancies, we suggest that screening for ETV6, RUNX1 and ANKRD26 mutations should be performed in all subjects with autosomal dominant thrombocytopenia and normal platelet size. PMID- 27365489 TI - Specific antibody deficiency and autoinflammatory disease extend the clinical and immunological spectrum of heterozygous NFKB1 loss-of-function mutations in humans. PMID- 27365490 TI - Bone healing in multiple myeloma: a prospective evaluation of the impact of first line anti-myeloma treatment. PMID- 27365491 TI - A third of British describe NHS funding crisis as "severe". PMID- 27365492 TI - Decline in genital warts diagnoses among young women and young men since the introduction of the bivalent HPV (16/18) vaccination programme in England: an ecological analysis. AB - BACKGROUND: For several decades, diagnoses of genital warts at genitourinary medicine (GUM) clinics in England had been increasing. In 2008, a national human papillomavirus (HPV) vaccination programme was introduced using the bivalent vaccine (types 16 and 18 only). A decrease in genital warts was not anticipated. However, rates of genital warts in GUM clinics have declined significantly since the introduction of the vaccine. METHODS: Using data from GUM clinics across England, we analysed rates of genital warts by age, gender, sexual orientation and estimated vaccine coverage. RESULTS: The reduction in rates of genital warts diagnoses at GUM clinics between 2009 and 2014 was 30.6% among young women aged 15-19 years and 25.4% among same age heterosexual young men. Overall there was an association showing higher warts reduction with increasing vaccination coverage with the largest declines in warts diagnoses observed in young women aged 15 years (50.9%) with the highest vaccination coverage. No such declines were observed in men who have sex with men (MSM) of the same age. CONCLUSION: The results of these ecological analyses are strongly in keeping with the bivalent HPV vaccine providing modest protection against genital warts. PMID- 27365494 TI - GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines. PMID- 27365493 TI - Marginal role for 53 common genetic variants in cardiovascular disease prediction. AB - OBJECTIVE: We investigated discrimination and calibration of cardiovascular disease (CVD) risk scores when genotypic was added to phenotypic information. The potential of genetic information for those at intermediate risk by a phenotype based risk score was assessed. METHODS: Data were from seven prospective studies including 11 851 individuals initially free of CVD or diabetes, with 1444 incident CVD events over 10 years' follow-up. We calculated a score from 53 CVD related single nucleotide polymorphisms and an established CVD risk equation 'QRISK-2' comprising phenotypic measures. The area under the receiver operating characteristic curve (AUROC), detection rate for given false-positive rate (FPR) and net reclassification improvement (NRI) index were estimated for gene scores alone and in addition to the QRISK-2 CVD risk score. We also evaluated use of genetic information only for those at intermediate risk according to QRISK-2. RESULTS: The AUROC was 0.635 for QRISK-2 alone and 0.623 with addition of the gene score. The detection rate for 5% FPR improved from 11.9% to 12.0% when the gene score was added. For a 10-year CVD risk cut-off point of 10%, the NRI was 0.25% when the gene score was added to QRISK-2. Applying the genetic risk score only to those with QRISK-2 risk of 10%-<20% and prescribing statins where risk exceeded 20% suggested that genetic information could prevent one additional event for every 462 people screened. CONCLUSION: The gene score produced minimal incremental population-wide utility over phenotypic risk prediction of CVD. Tailored prediction using genetic information for those at intermediate risk may have clinical utility. PMID- 27365495 TI - Environmental Contamination and Persistence of Ebola Virus RNA in an Ebola Treatment Center. AB - BACKGROUND: Ebola viruses (EBOVs) are primarily transmitted by contact with infected body fluids. Ebola treatment centers (ETCs) contain areas that are exposed to body fluids through the care of patients suspected or confirmed to have EBOV disease. There are limited data documenting which areas/fomites within ETCs pose a risk for potential transmission. This study conducted environmental surveillance in 2 ETCs in Freetown, Sierra Leone, during the 2014-2016 West African Ebola outbreak. METHODS: ETCs were surveyed over a 3-week period. Sites to be swabbed were identified with input from field personnel. Swab samples were collected and tested for the presence of EBOV RNA. Ebola-positive body fluid impregnated cotton pads were serially sampled. RESULTS: General areas of both ETCs were negative for EBOV RNA. The immediate vicinity of patients was the area most likely to be positive for EBOV RNA. Personal protective equipment became positive during patient care, but chlorine solution washes rendered them negative. CONCLUSIONS: Personal protective equipment and patient environs do become positive for EBOV RNA, but careful attention to decontamination seems to remove it. EBOV RNA was not detected in general ward spaces. Careful attention to decontamination protocols seems to be important in minimizing the presence of EBOV RNA within ETC wards. PMID- 27365496 TI - Smoking status and 30-day mortality in patients undergoing pulmonary resections. AB - BACKGROUND: Smoking status has not been shown to have a significant effect on 30 day mortality after potentially curative resectional surgery for non-small-cell lung cancer, and this is reflected in the guidelines of the National Institute for Health and Care Excellence in the United Kingdom. METHODS: A validated prospective thoracic surgery database of consecutive patients undergoing potentially curative resection at a single institution was analyzed. Univariate and propensity analyses of 30-day mortality were performed. RESULTS: Univariate analysis identified 30-day mortality as significantly lower in current smokers (n = 852, 2.6%) than ex-smokers (n = 1587, 4.9%; p < 0.001). Propensity 1:1 matching of male patients resulted in 727 current smokers being matched to 727 ex-smokers. The overall balance test (chi(2 )= 6.1, degrees of freedom = 8, p = 0.6), indicated a good match. After propensity matching, the mortality rate was significantly higher in current smokers (p = 0.01). CONCLUSIONS: Current smokers and ex-smokers are statistically different with regard to risk factors for death. This results in a skewed population of current and ex-smokers undergoing resection for non-small-cell lung cancer. Development of a risk model for 30-day mortality revealed that current smokers have a lower predicted 30-day mortality than ex-smokers, a finding that is counterintuitive. Propensity matching balanced the current and ex-smoker groups to correct for group differences. Analysis after propensity matching identified current smoking as a significant factor determining 30-day mortality. PMID- 27365497 TI - Medical data of 655 000 Americans put up for sale by hacker. PMID- 27365500 TI - Oxygen desaturation during a 6-min walk identifies a COPD phenotype with an increased risk of morbidity and mortality. PMID- 27365499 TI - The K153Del PRPH2 mutation differentially impacts photoreceptor structure and function. AB - Peripherin 2 (Prph2) is a photoreceptor tetraspanin, and deletion of codon 153 (K153Delta) leads to retinitis pigmentosa, pattern dystrophy, and fundus flavimaculatus in the same family. To study this variability, we generated a K153Delta-Prph2 knockin mouse. K153Delta-Prph2 cannot form the complexes required for outer segment formation, and in cones cannot interact with its binding partner rod outer segment membrane protein 1. K153Delta causes dominant defects in rod and cone function; however, rod but not cone ultrastructure is improved by the presence of K153Delta-Prph2. Likewise, supplementation of K153Delta heterozygotes with WT-Prph2 results in structural but not functional improvements. These results support the idea that mutations may differentially affect Prph2's role as a structural component, and its role as a functional protein key for organizing membrane domains for cellular signalling. These roles may be different in rods and cones, thus contributing to the phenotypic heterogeneity that characterizes diseases associated with Prph2 mutations. PMID- 27365501 TI - Maternal passive smoking and the risk of developing wheeze in children: how should we deal with it? PMID- 27365498 TI - Loss of MeCP2 in the rat models regression, impaired sociability and transcriptional deficits of Rett syndrome. AB - Mouse models of the transcriptional modulator Methyl-CpG-Binding Protein 2 (MeCP2) have advanced our understanding of Rett syndrome (RTT). RTT is a 'prototypical' neurodevelopmental disorder with many clinical features overlapping with other intellectual and developmental disabilities (IDD). Therapeutic interventions for RTT may therefore have broader applications. However, the reliance on the laboratory mouse to identify viable therapies for the human condition may present challenges in translating findings from the bench to the clinic. In addition, the need to identify outcome measures in well-chosen animal models is critical for preclinical trials. Here, we report that a novel Mecp2 rat model displays high face validity for modelling psychomotor regression of a learned skill, a deficit that has not been shown in Mecp2 mice. Juvenile play, a behavioural feature that is uniquely present in rats and not mice, is also impaired in female Mecp2 rats. Finally, we demonstrate that evaluating the molecular consequences of the loss of MeCP2 in both mouse and rat may result in higher predictive validity with respect to transcriptional changes in the human RTT brain. These data underscore the similarities and differences caused by the loss of MeCP2 among divergent rodent species which may have important implications for the treatment of individuals with disease-causing MECP2 mutations. Taken together, these findings demonstrate that the Mecp2 rat model is a complementary tool with unique features for the study of RTT and highlight the potential benefit of cross-species analyses in identifying potential disease relevant preclinical outcome measures. PMID- 27365502 TI - Supported self-management for COPD: making progress, but there are still challenges. PMID- 27365503 TI - Computed tomography-derived pathological phenotypes in COPD. PMID- 27365504 TI - Interventions to modify physical activity in patients with COPD: where do we go from here? PMID- 27365505 TI - Provocative testing of the pulmonary circulation: advances and unresolved issues. PMID- 27365506 TI - Perioperative screening for obstructive sleep apnoea and treatment outcomes: where are the data? PMID- 27365507 TI - Exercise: shifting fluid and sleep apnoea away. PMID- 27365508 TI - Idiopathic pulmonary fibrosis: another step in understanding the burden of this disease. PMID- 27365509 TI - Preventing and controlling tuberculosis among refugees in Europe: more is needed. PMID- 27365510 TI - Preventing and controlling tuberculosis among refugees in Europe: more needed for high-risk populations. PMID- 27365511 TI - Treatment options for isolated locoregional recurrences of nonsmall cell lung cancer after surgery: yes, radiation therapy too! PMID- 27365512 TI - Radiation therapy for post-operative recurrence: yes, but only for limited indications. PMID- 27365513 TI - Readmission in COPD patients: should we consider it a marker of quality of care or a marker of a more severe disease with a worse prognosis? PMID- 27365514 TI - Readmission in COPD patients: should we consider it a marker of quality of care or a marker of a more severe disease with a worse prognosis? PMID- 27365515 TI - European idiopathic pulmonary fibrosis Patient Charter: a missed opportunity. PMID- 27365516 TI - European idiopathic pulmonary fibrosis Patient Charter: a missed opportunity. PMID- 27365517 TI - "Exercise pulmonary haemodynamics: a test in search of purpose." J. Gerry Coghlan and Harm Jan Bogaard. Eur Respir J 2016; 47: 1315-1317. PMID- 27365519 TI - ERJ July Podcast: tuberculosis prevention and control in refugees. PMID- 27365518 TI - "Tidal flow variability measured by impedance pneumography relates to childhood asthma risk." Ville-Pekka Seppa, Anna S. Pelkonen, Anne Kotaniemi-Syrjanen, Jari Viik, Mika J. Makela and L. Pekka Malmberg. Eur Respir J 2016; 47: 1687-1696. PMID- 27365520 TI - Schroeder and Roberts. Is Tradition Trumping Evidence in the Treatment of Young, Febrile Infants? Hospital Pediatrics. 2016;6(4):252-253. PMID- 27365522 TI - SonoTip Pro EBUS-TBNA needle - the need for comparative studies with the Vizishot 21 guage needle. PMID- 27365521 TI - Evaluation of oral care to prevent oral mucositis in estrogen receptor-positive metastatic breast cancer patients treated with everolimus (Oral Care-BC): randomized controlled phase III trial. AB - This is a randomized, multi-center, open-label, phase III study to evaluate the efficacy of professional oral care in preventing oral mucositis induced by everolimus in postmenopausal estrogen receptor-positive metastatic breast cancer. Patients will be randomized into professional oral care and control groups (1:1 ratio). All patients will receive everolimus with exemestane and will continue everolimus until disease progression. In the professional oral care group, patients will receive teeth surface cleaning, scaling and tongue cleaning before starting everolimus, and will continue to receive professional oral care weekly from oral surgeons throughout the 8 week treatment. In the control group, patients will brush their own teeth and gargle with 0.9% sodium chloride solution or water. The primary endpoint is the incidence of all grades of oral mucositis. Target accrual is 200 patients with a two-sided type I error rate of 5% and 80% power to detect 25% risk reduction. PMID- 27365523 TI - Editorial for Urologic Cancer in Asia Series'. PMID- 27365524 TI - Combination chemotherapy with methotrexate and vinblastine for surgically unresectable, aggressive fibromatosis. AB - OBJECTIVE: To elucidate the clinical benefit and safety of low-dose chemotherapy using methotrexate and vinblastine in patients (mostly adults) with progressive and/or symptomatic fibromatosis. METHODS: Patients were enrolled if they were treated with methotrexate and vinblastine chemotherapy for recurrences after surgical excision or newly diagnosed aggressive fibromatosis that was not amenable to surgical resection at the Korea University Medical Center from May 2008 to February 2016. RESULTS: Twenty-two patients were treated with this regimen, and 21 were eligible for safety and efficacy analysis. Eleven (52%) of 21 patients showed a documented partial response (PR), and 11 showed stable disease (SD) by the end of treatment. All the patients who achieved PR reported a significant reduction in pain and improvement in the function of the affected lesions. Median progression-free survival was not reached at the time of analysis. The most common adverse event was abnormalities of the liver transaminases (overall 84.2%). The most common grade 3 or higher toxicity was neutropenia (36.8%), but no febrile neutropenic event was observed. The elevated levels of transaminases were normalized by reducing the dose of methotrexate or delaying treatment. CONCLUSIONS: Low-dose chemotherapy with methotrexate and vinblastine for 1 year was effective and well tolerated by adult patients with aggressive, recurrent fibromatosis. PMID- 27365526 TI - Editorial: Treg potency and the importance of being fit. PMID- 27365525 TI - Prevalence of infertility and help seeking among 15 000 women and men. AB - STUDY QUESTION: What is the prevalence of infertility and of help seeking among women and men in Britain? SUMMARY ANSWER: One in eight women and one in ten men aged 16-74 years had experienced infertility, defined by unsuccessfully attempting pregnancy for a year or longer, and little more than half of these people sought medical or professional help. WHAT IS KNOWN ALREADY: Estimates of infertility and help seeking in Britain vary widely and are not easily comparable because of different definitions and study populations. STUDY DESIGN, SIZE, DURATION: A cross-sectional population survey was conducted between 2010 and 2012 with a sample of 15 162 women and men aged 16-74 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants completed the Natsal-3 questionnaire, using computer-assisted personal interviewing (CAPI) and computer-assisted self interview (CASI). MAIN RESULTS AND THE ROLE OF CHANCE: The reported prevalence of infertility was 12.5% (CI 95% 11.7-13.3) among women and 10.1% (CI 95% 9.2-11.1) among men. Increased prevalence was associated with later cohabitation with a partner, higher socio-economic status and, for those who had a child, becoming parents at older ages. The reported prevalence of help seeking was 57.3% (CI 95% 53.6-61.0) among women and 53.2% (CI 95% 48.1-58.1) among men. Help seekers were more likely to be better educated and in higher status occupations and, among those who had a child, to have become parents later in life. LIMITATIONS, REASONS FOR CAUTION: These data are cross-sectional so it is not possible to establish temporality or infer causality. Self-reported data may be subject to recall bias. WIDER IMPLICATIONS OF THE FINDINGS: The study provides estimates of infertility and help seeking in Britain and the results indicate that the prevalence of infertility is higher among those delaying parenthood. Those with higher educational qualifications and occupational status are more likely to consult with medical professionals for fertility problems than others and these inequalities in help seeking should be considered by clinical practice and public health. STUDY FUNDING/COMPETING INTERESTS: Funding was provided by grants from the Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health. AMJ is a Governor of the Wellcome Trust. Other authors have no competing interests. PMID- 27365527 TI - Editorial: Decoding the macrophage phagosomal environment: the hunt for key reductases is on. PMID- 27365528 TI - The microenvironment of visceral adipose tissue and liver alter natural killer cell viability and function. AB - The role of NK cells in visceral adipose tissue (VAT) and liver inflammation in obesity is not fully understood. This study investigated the frequency, cytokine expression, chemokine receptor, and cytotoxicity receptor profile of NK cells in the blood, omentum, and liver of patients with the obesity-associated cancer, oesophageal adenocarcinoma (OAC). The effect of chronically inflamed tissue microenvironments on NK cell viability and function was also examined. We identified significantly lower NK cell frequencies in the liver of OAC patients compared with healthy controls and within the omentum and liver of OAC patients compared with blood, whereas IL-10-producing populations were significantly higher. Interestingly, our data suggest that reduced frequencies of NK cells in omentum and liver of OAC patients are not a result of impaired NK cell chemotaxis to these tissues. In fact, our functional data revealed that secreted factors from omentum and liver of OAC patients induce significant levels of NK cell death and lead to reduced percentages of TNF-alpha+ and NKP46+ NK cells and higher frequencies of IL-10-producing NK cells. Together, these data suggest that the omental and hepatic microenvironments of OAC patients alter the NK cell phenotype to a more anti-inflammatory homeostatic role. PMID- 27365529 TI - A novel bacterial transport mechanism of Acinetobacter baumannii via activated human neutrophils through interleukin-8. AB - Hospital-acquired infections as a result of Acinetobacter baumannii have become problematic because of high rates of drug resistance. Although neutrophils play a critical role in early protection against bacterial infection, their interactions with A. baumannii remain largely unknown. To elucidate the interactions between A. baumannii and human neutrophils, we cocultured these cells and analyzed them by microscopy and flow cytometry. We found that A. baumannii adhered to neutrophils. We next examined neutrophil and A. baumannii infiltration into Matrigel basement membranes by an in vitro transmigration assay. Neutrophils were activated by A. baumannii, and invasion was enhanced. More interestingly, A. baumannii was transported together by infiltrating neutrophils. Furthermore, we observed by live cell imaging that A. baumannii and neutrophils moved together. In addition, A. baumannii-activated neutrophils showed increased IL-8 production. The transport of A. baumannii was suppressed by inhibiting neutrophil infiltration by blocking the effect of IL-8. A. baumannii appears to use neutrophils for transport by activating these cells via IL-8. In this study, we revealed a novel bacterial transport mechanism that A. baumannii exploits human neutrophils by adhering to and inducing IL-8 release for bacterial portage. This mechanism might be a new treatment target. PMID- 27365530 TI - Lessons from a double-transgenic neutrophil approach to induce antiproteinase 3 antibody-mediated vasculitis in mice. AB - ANCA to either PR3 or MPO are found in patients with necrotizing vasculitis and glomerulonephritis. ANCA binding to their target antigens on neutrophils and subsequent neutrophil activation are pivotal disease mechanisms that lead to vascular inflammation and necrosis. ANCA interaction with PR3 is more complex than with MPO as the neutrophil-specific CD177 receptor is involved in PR3 surface expression and PR3-ANCA-induced neutrophil activation. Modeling human disease is important to clinical research. Highly successful mouse models of MPO ANCA vasculitis exist; however, recapitulating PR3-ANCA vasculitis has not been successful. We generated double-transgenic (DT) mice that expressed human PR3 and CD177 under a myeloid-specific huMRP8 promoter in an attempt to model PR3-ANCA vasculitis. DT mice strongly expressed the human transgenes in and on murine neutrophils and bound murine and human anti-PR3 antibodies. Nevertheless, passive transfer of these antibodies into LPS-primed DT mice or immunization of C57BL/6 mice with human PR3 followed by irradiation and transplantation of DT bone marrow failed to induce glomerulonephritis. Further analyses revealed that anti-PR3 antibodies did not activate DT neutrophils as shown by superoxide generation. Moreover, we found that mice did not properly process human pro-PR3 into mature PR3 and, consequently, the signaling complex between PR3, CD177, and CD11b, which promotes neutrophil activation by anti-PR3 antibodies, failed to form. We conclude that important species differences in PR3 and CD177 exist between men and mice that prevented successful generation of a murine anti-PR3 antibody model. PMID- 27365532 TI - Analysis of the HLA-DR peptidome from human dendritic cells reveals high affinity repertoires and nonconventional pathways of peptide generation. AB - Dendritic cells (DCs) are the major professional APCs of the immune system; however, their MHC-II-associated peptide repertoires have been hard to analyze, mostly because of their scarce presence in blood and tissues. In vitro matured human monocyte-derived DCs (MoDCs) are widely used as professional APCs in experimental systems. In this work, we have applied mass spectrometry to identify the HLA-DR-associated self-peptide repertoires from small numbers of mature MoDCs (~5 * 106 cells), derived from 7 different donors. Repertoires of 9 different HLA DR alleles were defined from analysis of 1319 peptides, showing the expected characteristics of MHC-II-associated peptides. Most peptides identified were predicted high binders for their respective allele, formed nested sets, and belonged to endo-lysosomal pathway-degraded proteins. Approximately 20% of the peptides were derived from cytosolic and nuclear proteins, a recurrent finding in HLA-DR peptide repertoires. Of interest, most of these peptides corresponded to single sequences, did not form nested sets, and were located at the C terminus of the parental protein, which suggested alternative processing. Analysis of cleavage patterns for terminal peptides predominantly showed aspartic acid before the cleavage site of both C- and N-terminal peptides and proline immediately after the cleavage site in C-terminal peptides. Proline was also frequent next to the cut sites of internal peptides. These data provide new insights into the Ag processing capabilities of DCs. The relevance of these processing pathways and their contribution to response to infection, tolerance induction, or autoimmunity deserve further analysis. PMID- 27365533 TI - Plastic restriction of HIV-1 replication in human macrophages derived from M1/M2 polarized monocytes. AB - M1/M2 cytokine-dependent polarization of primary human MDMs has been shown to contain CCR5-dependent (R5) HIV-1 replication. In this study, a similar effect was achieved when monocytes were first polarized toward M1 or M2 and were infected 7 d after their differentiation into MDMs, regardless of whether the cytokines were removed 18 h after cell stimulation or were left in culture. Unlike polarized MDMs, no significant down-regulation of CD4 from the cell surface was observed in MDMs derived from M1/M2-polarized monocytes. A second stimulation of MDMs differentiated from M1/M2 monocytes with the opposite polarizing cytokines converted the virus replication profile according to the new stimuli. The expression of M1 and M2 markers (i.e., APOBEC3A and DC-SIGN, respectively) was induced by MDM stimulation with the opposite cytokines, although it also persisted in cells according to their first stimulatory condition. Thus, stimulation of monocytes with M1- and M2-inducing cytokines leads to a restriction of HIV-1 replication when these cells are infected several days later as differentiated MDMs. These observations imply that activation of circulating monocytes significantly influences their capacity to either support or restrict HIV-1 replication, once extravasated, and eventually to become infected as tissue macrophages. PMID- 27365531 TI - FcgammaR mediates TLR2- and Syk-dependent NLRP3 inflammasome activation by inactivated Francisella tularensis LVS immune complexes. AB - IgG (mAb)-opsonized, inactivated Francisella tularensis LVS (iFt-mAb) enhances TLR2-dependent IL-6 production by macrophages via Fcgamma receptors (FcgammaR). In mice, vaccination with iFt-mAb provides IgA-dependent protection against lethal challenge with Ft LVS. Because inflammasome maturation of IL-1beta is thought important for antibody-mediated immunity, we considered the possibility that iFt-mAb elicits an FcgammaR-dependent myeloid cell inflammasome response. Herein, we find that iFt-mAb enhances macrophage and dendritic cell IL-1beta responses in a TLR2- and FcgammaR-dependent fashion. Although iFt-mAb complexes bind FcgammaR and are internalized, sensing of cytosolic DNA by absent in melanoma 2 (AIM2) is not required for the IL-1beta response. In contrast, ASC, caspase-1, and NLR family pyrin domain-containing 3 (NLRP3) are indispensable. Further, FcgammaR-mediated spleen tyrosine kinase (Syk) signaling is required for this NLRP3-dependent IL-1beta response, but the alternative IL-1beta convertase caspase-8 is insufficient. Finally, iFt-mAb-vaccinated wild-type mice exhibit a significant delay in time to death, but IL-1R1- or Nlrp3-deficient mice vaccinated in this way are not protected and lack appreciable Francisella specific antibodies. This study demonstrates that FcgammaR-mediated Syk activation leads to NLRP3 inflammasome-dependent IL-1beta production in macrophages and suggests that an Nlrp3- and IL-1R-dependent process contributes to the IgA response important for protection against Ft LVS. These findings extend our understanding of cellular responses to inactivated pathogen-opsonized vaccine, establish FcgammaR-elicited Syk kinase-mediated NLRP3 inflammasome activation, and provide additional insight toward understanding crosstalk between TLR and FcgammaR signals. PMID- 27365536 TI - Erratum. PMID- 27365534 TI - A tale of two sites: how inflammation can reshape the microbiomes of the gut and lungs. AB - Inflammation can directly and indirectly modulate the bacterial composition of the microbiome. Although studies of inflammation primarily focus on its function to negatively select against potential pathogens, some bacterial species have the ability to exploit inflammatory byproducts for their benefit. Inflammatory cells release reactive nitrogen species as antimicrobial effectors against infection, but some facultative anaerobes can also utilize the increase in extracellular nitrate in their environment for anaerobic respiration and growth. This phenomenon has been studied in the gastrointestinal tract, where blooms of facultative anaerobic Gammaproteobacteria, primarily Escherichia coli, often occur during colonic inflammation. In cystic fibrosis, Pseudomonas aeruginosa, another Gammaproteobacteria facultative anaerobe, can reduce nitrogen for anaerobic respiration and it blooms in the airways of the chronically inflamed cystic fibrosis lung. This review focuses on the evidence that inflammation can provide terminal electron acceptors for anaerobic respiration and can support blooms of facultative anaerobes, such as E. coli and P. aeruginosa in distinct, but similar, environments of the inflamed gastrointestinal and respiratory tracts. PMID- 27365535 TI - Long-Term Exposure to Air Pollution and Increased Risk of Membranous Nephropathy in China. AB - The effect of air pollution on the changing pattern of glomerulopathy has not been studied. We estimated the profile of and temporal change in glomerular diseases in an 11-year renal biopsy series including 71,151 native biopsies at 938 hospitals spanning 282 cities in China from 2004 to 2014, and examined the association of long-term exposure to fine particulate matter of <2.5 MUm (PM2.5) with glomerulopathy. After age and region standardization, we identified IgA nephropathy as the leading type of glomerulopathy, with a frequency of 28.1%, followed by membranous nephropathy (MN), with a frequency of 23.4%. Notably, the adjusted odds for MN increased 13% annually over the 11-year study period, whereas the proportions of other major glomerulopathies remained stable. During the study period, 3-year average PM2.5 exposure varied among the 282 cities, ranging from 6 to 114 MUg/m3 (mean, 52.6 MUg/m3). Each 10 MUg/m3 increase in PM2.5 concentration associated with 14% higher odds for MN (odds ratio, 1.14; 95% confidence interval, 1.10 to 1.18) in regions with PM2.5 concentration >70 MUg/m3 We also found that higher 3-year average air quality index was associated with increased risk of MN. In conclusion, in this large renal biopsy series, the frequency of MN increased over the study period, and long-term exposure to high levels of PM2.5 was associated with an increased risk of MN. PMID- 27365537 TI - Voltammetric Determination of Dinonyl Diphenylamine and Butylated Hydroxytoluene in Mineral and Synthetic Oil. AB - A method is reported for the determination of diphenylamine and butylated hydroxytoluene in mineral and synthetic oil. The procedure used differential pulse voltammetry with a glassy carbon electrode. This method was then used for determining these antioxidants in supporting electrolyte consisting of dilute sulfuric acid and sodium dodecyl sulfonate in ethanol. Anodic peaks were obtained for both analytes. Oxidation peaks at 250 mV were observed from a mixture of butylated hydroxytoluene and dinonyl diphenylamine, allowing their simultaneous determination. This approach was successfully used for the determination of dinonyl diphenylamine and butylated hydroxytoluene in fortified mineral and synthetic oils with good accuracy and precision. PMID- 27365538 TI - The German IVF Register as an Instrument to Document Assisted Reproductive Technologies. AB - The German IVF Register (Deutsches IVF-Register [D.I.R]) has been collecting and publishing data on the use of IVF and related methods in Germany since 1982. It is the only institution which provides information for all of Germany on procedures and their success rates. For this reason it plays an important role in the provision of information to the public, to patients, political decision makers and the scientific community. However, the register does not have the data of all centers offering treatment in Germany nor does it have complete datasets on all reported treatments. The register accepts retrospective data entries, it does not publish the success rates of individual centers and up until 2015 it did not provide a summary of information which was suitable for non-specialists. The D.I.R has been the focus of criticism in the past. Even today, the information it provides to the scientific community, the public, political decision-makers and potential patients on the outcomes of assisted reproduction is insufficient. The documentation of reproductive medicine procedures in other countries is much more meaningful. PMID- 27365539 TI - The German Middleway as Precursor for Single Embryo Transfer. A Retrospective Data-analysis of the Dusseldorf University Hospital's Interdisciplinary Fertility Centre - UniKiD. AB - Introduction: Patients receiving fertility treatment in Germany appear to be disadvantaged in comparison to those in other countries due to the restrictive Embryo Protection Act ("Embryonenschutzgesetz, ESchG"), which prohibits the selection of a "top" embryo. The so-called German Middleway ("Deutscher Mittelweg, DMW") now provides for a liberal interpretation of the ESchG by allowing the culture of numerous pronuclear stages (2PN stage). Materials and Methods: Retrospective cohort study of 2 assisted reproduction treatment cycles in n = 400 patients between the ages of 21 and 45 years, either treated 2* conservatively or 1* conservatively and 1* liberally according to DMW. Results: Pregnancy was achieved in 35 % of patients in the DMW group and 31 % of controls. The birth rate among controls was 28.5 % and 30.5 % in the DMW group. Most pregnancies resulted from the culture of 4 * 2PN stages. Conclusion: Patients in the DMW group had significantly higher pregnancy and birth rates compared to their previous cycles despite significantly increased age and significantly fewer transferred embryos. Key factors were the number of 2PNs generated and the quality of embryos transferred. Thus it can be assumed that particularly older patients with adequate ovarian reserves will benefit from DMW, i.e. the transfer of fewer embryos of the best possible quality. PMID- 27365540 TI - Diagnosis of Endometrial-Factor Infertility: Current Approaches and New Avenues for Research. AB - Over the last decade, research to improve success rates in reproductive medicine has focused predominantly on the understanding and optimization of embryo quality. However, the emergence of personalized medicine in ovulation induction and embryology has shifted the focus to assessing the individual status of the endometrium. The endometrium is considered receptive during an individually defined period, the window of implantation (WOI), when the mother permits a blastocyst to attach and implant. This individual receptivity status can now be objectively diagnosed using the endometrial receptivity array (ERA) developed in 2011. The ERA, together with a computational algorithm, detects the unique transcriptomic signature of endometrial receptivity by analyzing 238 differentially expressed genes and reliably predicting the WOI. We and others have illustrated the utility of this personalized diagnostic approach to discriminate between individual physiological variation in endometrial receptivity and unknown endometrial pathology, deemed as causal in recurrent implantation failure (RIF). An international randomized controlled trial ("The ERA as a diagnostic guide for personalized embryo transfer." ClinicalTrials.gov Identifier: NCT01954758) is underway to determine the clinical value of this endometrial diagnostic intervention in the work-up for reproductive care. In this review, we analyse the current clinical practice in the diagnosis of the endometrial factor together with new avenues of research. PMID- 27365541 TI - MicroRNA Profile of Granulosa Cells after Ovarian Stimulation Differs According to Maturity of Retrieved Oocytes. AB - Background: Recent animal studies demonstrated that regulating the microRNA (miRNA) in granulosa cells (GCs) modulates the meiotic competence of oocytes. However, the difference in expression profiles of miRNAs in human GCs according to the maturity of the oocyte still remains to be elucidated. Objective: This observational study investigated whether the miRNA profile of human GCs differs according to the maturity of the retrieved oocyte after controlled ovarian stimulation for in vitro fertilization (IVF). Methods: Ten women who underwent ovarian stimulation cycles with GnRH agonist long protocols were recruited. The follicular fluid (FF) from dominant follicles was individually aspirated at oocyte retrieval. Oocytes were divided into two groups according to oocyte maturity ("mature group" vs. "immature group"). GCs were collected from the FF and miRNA was analyzed using real-time PCR. Results: Mean number of MII oocytes in the mature group was 1.6 +/- 0.9 with none in the immature group (p = 0.008). Mean number of MI oocytes was 5.6 +/- 2.1 in the mature group and 1.0 +/- 0.0 in the immature group (p = 0.008). The total number of retrieved oocytes was 8.8 +/- 1.9 in the mature group and 2.0 +/- 1.2 in the immature group (p = 0.008). The GCs of the mature group showed a significantly lower expression of hsa-let-7b compared to the GCs of the immature group (p < 0.001). Conclusion: Taken together, the miRNA expression profiles of human GCs obtained from dominant follicles are associated with maturity of the adjacent oocyte and may be useful as a prognosticator of IVF outcome. PMID- 27365542 TI - Osteopontin and Integrin alphavbeta3 Expression during the Implantation Window in IVF Patients with Elevated Serum Progesterone and Oestradiol Level. AB - Background: To explore whether endometrial receptivity is determined by osteopontin (OPN) and integrin alphavbeta3 expression in women with elevated serum progesterone (P) and/or oestradiol (E2) who are undergoing in vitro fertilisation (IVF). Methods: According to serum hormone levels on the day of HCG administration, 33 infertile women were divided into 3 groups: the high E2, high P, and high E2 and P groups. The control group included 11 fertile, healthy women. Endometrial biopsy was performed on ovulation day + 7 to + 8 for all study participants, and the mRNA and protein expression levels of OPN and integrin alphavbeta3 were analyzed. Result: No statistically significant differences regarding OPN and integrin alphavbeta3 expression were found between infertile patients in the high P, high E2, high E2 and P and control groups. There was no significant correlation between OPN and integrin alphavbeta3 staining intensity during the implantation window biopsy in any of the groups studied. Conclusion: Endometrial OPN and integrant alphavbeta3 expression/co-expression is not impaired during the window of implantation in patients with high P, high E2, or high E2 and P levels. The clinical value of assessing endometrial receptivity with OPN and integrin alphavbeta3 seems to be uncertain. PMID- 27365543 TI - Avoiding OHSS: Controlled Ovarian Low-Dose Stimulation in Women with PCOS. AB - The polycystic ovary syndrome is a common endocrine disorder which influences outcome and potential risks involved with controlled ovarian stimulation for artificial reproductive techniques (ART). Concrete practical recommendations for the dosage of gonadotropins, the preferred protocol and preventive methods to avoid ovarian hyperstimulation syndrome (OHSS) are lacking. We present retrospective data of 235 individually calculated gonadotropin low-dose stimulations for ART in a single center from 2012 to 2014. Clinical data and outcome parameter of patients diagnosed with PCOS according to Rotterdam criteria (n = 39) were compared with patients without PCOS (n = 196). The starting dose of gonadotropins was individually calculated depending on patients' age, BMI, ovarian reserve, ovarian response in previous cycles, and diagnostic criteria of PCOS. Mean age and duration of infertility did not differ between the groups, whereas mean BMI (p = 0.007) and AMH (p < 0.001) were higher in the PCOS-group. A lower mean FSH-starting and maximum dose was administered to women with PCOS (p < 0.001). The biochemical pregnancy rate of 42.4 % and the clinical pregnancy rate of 32.2 % for PCOS-patients did not differ from those of the control group (42.2 % and 34.4 % respectively). Neither mild, nor moderate or severe manifestation of OHSS occurred significantly more often in patients with PCOS. Our study supports the use of a calculated low-dose FSH-stimulation strategy in ART for patients with PCOS. Further randomized clinical trials should confirm this strategy and lead to define individual risk factors for OHSS, which can be used for recommendation of safer ART-techniques like in vitro maturation. PMID- 27365544 TI - Antenatal Diagnosis of Dizygotic, Monochorionic Twins Following IVF/ICSI. AB - Monochorionic twins are usually monozygotic and thus usually have the same sex. A case of monochorionic diamniotic twins following IVF/ICSI and laser treatment of the zona pellucida ("assisted hatching") is presented in which partial embryo amalgamation appears to have occurred. Discordant sex between the twins was suspected on detailed antenatal ultrasound at 13 + 3 weeks gestation and was confirmed on subsequent examinations. The sexual phenotype at birth was female for one twin and male for the other. Placental histology confirmed the monochorionic, diamniotic situation. Cytogenetic analysis of both twins was carried out postpartum on various tissues. On karyotyping of blood lymphocytes the male and female twins each had one mosaic of male and female cells. Oral mucosal cells showed normal male and female karyotypes respectively. Analysis of urothelium showed a normal result for the male infant, and a weak gonosomal mosaic with an XX and XY constellation for the female infant. At least for blood lymphocytes, a diagnosis of chimerism was proven. PMID- 27365545 TI - Enhanced removal of nickel(II) ions from aqueous solutions by SDS-functionalized graphene oxide. AB - In this paper, a one-pot and easy-to-handle method at room temperature without additional chemicals for the modification of graphene oxide (GO) with surfactant is found. Removal of nickel (II) ions from aqueous solutions by GO and surfactant (sodium dodecyl sulphate) modified graphene oxide (SDS-GO) was studied spectrophotometrically at room temperature as a function of time, initial concentration and pH. Adsorption capacity of the adsorbent was increased dramatically (from 20.19 to 55.16 mg/g found by Langmuir model) due to the functionalization of the surface by SDS. The driving force of the adsorption of Ni(II) ions is electrostatic attraction and Ni(II) ions adsorbed on the GO surface chemically besides ion exchange. PMID- 27365546 TI - Determinants of Quality of Life in the Caregivers of Iranian War Survivors with Bilateral Lower-Limb Amputation after More than Two Decades. AB - BACKGROUND: Providing care to a disable relative at home exposes the caregiver to a potentially higher risk of physical and mental problems. We measured health related quality of life (HRQOL) and its determinants among the caregivers of the Iranian survivors of the Iran-Iraq war (1980-1988) with bilateral lower-limb amputation. METHODS: Data were collected from 464 individuals comprising war related bilateral lower-limb amputees (n=232) and their caregivers (n=232) in January 2015 in Shiraz, Iran. The 36-Item Short-Form Health Survey (SF-36) questionnaire was used to evaluate the caregivers' QOL. Logistic regression analysis was performed to determine the most significant contributing factors. RESULTS: The mean age of the caregivers and the amputees was 39.4+/-6.2 and 42.5+/-6.2 years, respectively. The mean duration of disability was 22.8+/-3.9 years in the amputees. Most of the caregivers were reported to be in their first marriage. The highest and lowest mean scores of the SF-36 domains in the sample population were observed for physical function (76.65+/-21.97) and bodily pain (53.54+/-24.95). QOL in the caregivers was significantly lower than that in a sample of the general Iranian female population (P<0.05). History of hospitalization during the preceding year of the study (OR: 2.23, 95% CI: 1.08 to 4.57, P=0.02) and mental health problems (OR: 1.79, 95% CI: 1.02 to 3.15, P=0.04) in the amputees constituted the most important predicting factors in the caregivers' QOL. CONCLUSION: The caregivers of the bilateral lower-limb amputees in the current study suffered from a poor QOL. Hospitalization and mental problems were the most significant contributing factors vis-a-vis the caregivers' HRQOL. Health care and services should, therefore, be provided to both amputees and their caregivers. PMID- 27365547 TI - Cardioprotective Effect of Extended Remote Ischemic Preconditioning in Patients Coronary Artery Bypass Grafting Undergoing: A Randomized Clinical Trial. AB - BACKGROUND: The cardioprotective effect of ischemic preconditioning has been known for many years. Since the temporary ischemia in the heart may cause lethal cardiac effects, the idea of creating ischemia in organs far from the heart such as limbs was raised as remote ischemic preconditioning (RIPC). We hypothesized that the extension of RIPC has more cardioprotective effect in patients undergoing coronary artery bypass graft (CABG) surgeries. METHODS: In this triple blind randomized clinical trial study, 96 patients were randomly divided into 3 groups and two blood pressure cuffs were placed on both upper and lower extremities. In group A, only upper extremity cuff and in group B upper limb and lower limb cuff was inflated intermittently and group C was the control group. RIPC was induced with three 5-min cycles of cuff inflation about 100 mmHg over the initial systolic blood pressure before starting cardiopulmonary bypass. The primary endpoints were troponin I and creatine phosphokinase-myoglobin isoenzyme (CK-MB). RESULTS: Six hours after the termination of CPB, there was a peak release of the troponin I level in all groups (group A=4.90 ng/ml, group B=4.40 ng/ml, and group C=4.50 ng/ml). There was a rise in plasma CK-MB in all groups postoperatively and there were not any significant differences in troponin I and CK-MB release between the three groups. CONCLUSION: RIPC induced by upper and lower limb ischemia does not reduce postoperative myocardial enzyme elevation in adult patients undergoing CABG. TRIAL REGISTRATION NUMBER: IRCT2012071710311N1. PMID- 27365548 TI - Effects of Ketamine on Neuronal Spontaneous Excitatory Postsynaptic Currents and Miniature Excitatory Postsynaptic Currents in the Somatosensory Cortex of Rats. AB - BACKGROUND: Ketamine is a commonly used intravenous anesthetic which produces dissociation anesthesia, analgesia, and amnesia. The mechanism of ketamine induced synaptic inhibition in high-level cortical areas is still unknown. We aimed to elucidate the effects of different concentrations of ketamine on the glutamatergic synaptic transmission of the neurons in the primary somatosensory cortex by using the whole-cell patch-clamp method. METHODS: Sprague-Dawley rats (11-19 postnatal days, n=36) were used to obtain brain slices (300 MUM). Spontaneous excitatory postsynaptic currents (data from 40 neurons) were recorded at a command potential of -70 mV in the presence of bicuculline (a competitive antagonist of GABAA receptors, 30 MUM) and strychnine (glycine receptor antagonist, 30 MUM). Miniature excitatory postsynaptic currents (data from 40 neurons) were also recorded when 1 MUM of tetrodotoxin was added into the artificial cerebrospinal fluid. We used GraphPad Prism5for statistical analysis. Significant differences in the mean amplitude and frequency were tested using the Student paired 2-tailed t test. Values of P<0.05 were considered significant. RESULTS: Different concentrations of ketamine inhibited the frequency and amplitude of the spontaneous excitatory postsynaptic currents as well as the amplitude of the miniature excitatory postsynaptic currents in a concentration dependent manner, but they exerted no significant effect on the frequency of the miniature excitatory postsynaptic currents. CONCLUSION: Ketamine inhibited the excitatory synaptic transmission of the neurons in the primary somatosensory cortex. The inhibition may have been mediated by a reduction in the sensitivity of the postsynaptic glutamatergic receptors. PMID- 27365549 TI - Diagnostic Value of the Urine Mucus Test in Childhood Masturbation among Children below 12 Years of Age: A Cross-Sectional Study from Iran. AB - BACKGROUND: Childhood masturbation (CM) is considered a variant of normal sexual behavior; however, it is commonly misdiagnosed as epilepsy and movement disorders. As the first study from Iran, we analyzed a large population of infants and children with CM in a case-control study and evaluated the value of mucus in urine analysis as an alternative diagnostic tool for CM. METHODS: A total of 623 children referred to the Pediatric Neurology Clinic of Imam Khomeini Hospital for an evaluation of seizure or movement disorders were studied between 2008 and 2011. Totally, 359 children were found to have masturbatory behaviors (Group A) and the rest (264) were assigned to Group B. CM was diagnosed by direct observation. Collected data comprised demographic characteristics, clinical and neurodevelopmental examinations, laboratory findings (particularly urine analysis), and electrocardiography. RESULTS: The age of the children with CM was below 12 years old, and the girl-to-boy ratio was 7:1. Mucus in urine was positive in 357 (99.44%) children in Group A and 22 (8.3%) in Group B (P<0.001). A significant correlation was found between the presence of mucus in urine and masturbatory behaviors (P<0.001). CONCLUSION: Our findings suggest that the presence of mucus in urine can be used as an alternative laboratory test in children with CM below 12 years old and even in infants (<=24 months old). Further studies are needed to confirm the results. PMID- 27365550 TI - The Accuracy of Body Mass Index and Gallagher's Classification in Detecting Obesity among Iranians. AB - BACKGROUND: The study was conducted to examine the comparability of the BMI and Gallagher's classification in diagnosing obesity based on the cutoff points of the gold standards and to estimate suitable cutoff points for detecting obesity among Iranians. METHODS: The cross-sectional study was comparative in nature. The sample consisted of 20,163 adults. The bioelectrical impedance analysis (BIA) was used to measure the variables of interest. Sensitivity, specificity, positive predictive power (PPV), and negative predictive power (NPV) were used to evaluate the comparability of the two classification methods in detecting obesity. RESULTS: The BMI wrongly classified 29% of the obese persons as overweight. In both classifications, as age increased, the accuracy of detecting obesity decreased. The Gallagher's classification is better than MBI in detecting obesity in men with the exception of those older than 59 years. In females, the BMI was better in determining sensitivity. In both classifications, either female or male, an increase in age was associated with a decrease in sensitivity and NPV with the exception of the BMI for the 18 year olds. Gallagher can correctly classify males and females who are less than 40 and 19 years old, respectively. CONCLUSION: Gallagher's classification is recommended for non-obese in both sexes and in obese males younger than 40 years old. The BMI is recommended for obese females. The suitable cutoff points for the BMI to detect obesity are 27.70 kg/m(2) for females and males, 27.70 kg/m(2) for females, and 27.30 kg/m(2) for males. PMID- 27365551 TI - Macrophage Immune Response Suppression by Recombinant Mycobacterium tuberculosis Antigens, the ESAT-6, CFP-10, and ESAT-6/CFP-10 Fusion Proteins. AB - BACKGROUND: Macrophage immune responses are affected by the secretory proteins of Mycobacterium tuberculosis (Mtb). This study aimed to examine the immune responses of macrophages to Mtb secretory antigens, namely ESAT-6, CFP-10, and ESAT-6/CFP-10. METHODS: THP-1 cells (a human monocytic cell line) were cultured and differentiated to macrophages by phorbol 12-myristate 13-acetate. The cytotoxicity of the recombinant Mtb proteins was assessed using the MTT assay. Two important immune responses of macrophages, namely NO and ROS production, were measured in response to the ESAT-6, CFP-10, and ESAT-6/CFP-10 antigens. The data were analyzed using one-way ANOVA with SPSS, version 16, and considered significant at P<0.05. RESULTS: The results showed that the ESAT-6, CFP-10, and ESAT-6/CFP-10 proteins markedly reduced macrophage immune response. The treatment of the THP-1-differentiated cells with ESAT-6, CFP-10, and ESAT-6/CFP-10 reduced NO and ROS production. The treated THP-1-differentiated cells exhibited less inducible NO synthase activity than did the untreated cells. No toxic effect on macrophage viability was observed for the applied proteins at the different concentrations. CONCLUSION: It seems that the decline in macrophage immune response is due to the suppression of NO and ROS production pathways without any effect on cell viability. PMID- 27365552 TI - Melatonin Reduces Cataract Formation and Aldose Reductase Activity in Lenses of Streptozotocin-induced Diabetic Rat. AB - BACKGROUND: The relationship between the high activity of aldose reductase (AR) and diabetic cataract formation has been previously investigated. The purpose of the present study was to determine the preventing effect of melatonin on streptozotocin (STZ)-induced diabetic cataract in rats. METHODS: 34 adult healthy male Sprague-Dawely rats were divided into four groups. Diabetic control and diabetic+melatonin received a single dose of STZ (50 mg/kg, intraperitoneally), whereas the normal control and normal+melatonin received vehicle. The melatonin groups were gavaged with melatonin (5 mg/kg) daily for a period of 8 weeks, whereas the rats in the normal control and diabetic control groups received only the vehicle. The rats' eyes were examined every week and cataract formation scores (0-4) were determined by slit-lamp microscope. At the end of the eighth week, the rats were sacrificed and markers of the polyol pathway and antioxidative (Glutathione, GSH) in their lens were determined. The levels of blood glucose, HbA1c and plasma malondialdhyde (MDA), as a marker of lipid peroxidation, were also measured. RESULTS: Melatonin prevented STZ-induced hyperglycemia by decreased blood glucose and HbA1c levels. Slit lamp examination indicated that melatonin delayed cataract progression in diabetic rats. The results revealed that melatonin feeding increased the GSH levels, decreased the activities of AR and sorbitol dehydrogenase (SDH) and sorbitol formation in catractous lenses as well as plasma MDA content. CONCLUSION: In summary, for the first time we demonstrated that melatonin delayed the formation and progression of cataract in diabetic rat lenses. PMID- 27365553 TI - Effect of Magnetic Fluid Hyperthermia on Implanted Melanoma in Mouse Models. AB - BACKGROUND: Nowadays, magnetic nanoparticles (MNPs) have received much attention because of their enormous potentials in many fields such as magnetic fluid hyperthermia (MFH). The goal of hyperthermia is to increase the temperature of malignant cells to destroy them without any lethal effect on normal tissues. To investigate the effectiveness of cancer therapy by magnetic fluid hyperthermia, Fe0.5Zn0.5Fe2O4 nanoparticles (FNPs) were used to undergo external magnetic field (f=515 kHz, H=100 G) in mice bearing implanted tumor. METHODS: FNPs were synthesized via precipitation and characterized using transmission electron microscopy (TEM), vibrating sample magnetometer, and Fourier transform infrared. For in vivo study, the mice bearing implanted tumor were divided into four groups (two mice per group), namely, control group, AMF group, MNPs group, and MNPs&AMF group. After 24 hours, the mice were sacrificed and each tumor specimen was prepared for histological analyses. The necrotic surface area was estimated by using graticule (Olympus, Japan) on tumor slides. RESULTS: The mean diameter of FNPs was estimated around 9 nm by TEM image and M versus H curve indicates that this particle is among superparamagnetic materials. According to histological analyses, no significant difference in necrosis extent was observed among the four groups. CONCLUSION: FNPs are biocompatible and have a good size for biomedical applications. However, for MFH approach, larger diameters especially in the range of ferromagnetic particles due to hysteresis loss can induce efficient heat in the target region. PMID- 27365554 TI - Status of Exudative Pleural Effusion in Adults of South Khorasan Province, Northeast Iran: Pleural Tuberculosis Tending toward Elderly. AB - The causes and situation of exudative pleural effusion vary from one area to another. A cross-sectional study was conducted on 327 patients with exudative pleural effusion in South Khorasan province (Iran). The patients were older than 12 years and comprised 172 (52.6%) males and 155 (47.4%) females. The study commenced in 2007 with seven years duration. The Light's criteria were used to define exudative effusion. Procedures including pleural fluid analysis, microbiological study, pleural biopsy, and systemic investigations were conducted to determine the special cause of pleural effusion. The mean age of the patients was 63.4+/-18.4 years. Malignancies, tuberculosis, and parapneumonia pleural exudation were diagnosed in 125 (38.2%), 48 (14.7%), and 45 (13.8%) cases, respectively. Among malignant effusions, metastasis from lung cancer made 48 (38.4%) of the cases. The origin of metastasis was not determined in 44 (35.2%) patients. The mean age of patients was not significantly different between malignant (66.9+/-14.3 years) and tuberculosis (63.9+/-19.7 years) cases (P=0.16). The older age of tuberculosis patients could be a new discussion point on the overall impression created on the subject of tuberculosis pleural exudation (TB-PLE) occurring in young people. PMID- 27365555 TI - Aqueous Extract of Anethum Graveolens L. has Potential Antioxidant and Antiglycation Effects. AB - The aim of this study was to assess the antiglycation and antioxidant properties of aqueous extract of Anethum graveolens (dill). In the in vivo and in vitro experiments, antioxidant properties, blood glucose, and AGEs formation were determined. Dill extract was given orally to healthy and diabetic rats. Our results illustrated that different concentrations of dill extract (0.125, 0.25, 0.5, and 1 mg/ml) have potential antiradical and antioxidant activity. Aqueous extract of dill significantly reduced AGEs formation and fructosamine levels, protein carbonyl and also thiol group's oxidation, amyloid cross-beta and fragmentation. After 2 months, blood glucose levels (P=0.006) and AGEs formation (P=0.003) significantly reduced in dill treated group compared with untreated diabetic animals. In conclusion, dill can be recommended as herbal medicine for the control and prevention of diabetic complications. PMID- 27365556 TI - miR-4284 and miR-4484 as Putative Biomarkers for Diffuse Large B-Cell Lymphoma. AB - Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. MicroRNAs (miRNAs) are endogenous small RNA, which can regulate gene expression at the post-transcriptional level. MiRNA profiling has shown a great potential as novel diagnostic and prognostic biomarkers. The present study was performed at the Nemazee Teaching Hospital (Shiraz, Iran) from 2011 to 2013. The aim of this study was to assess the deregulation of miRNAs profiles in DLBL against hyperplasic reactive lymph node as a normal. This could serve as a biomarker for DLBL. The miRCURY LNATM microarray was used on the total RNA, which was extracted from formalin-fixed paraffin-embedded tissue of 24 de novo diffuse large B-cell lymphoma patients and 14 normal lymph nodes. The greatest changes were detected in miR-4284 and miR-4484 level in patient's lymphoma samples. These miRNAs can act as a diagnostic biomarker for DLBL. PMID- 27365557 TI - Hybrid Ameloblastoma of the Maxilla: A Puzzling Pathology. AB - Ameloblastomas are slow growing, locally invasive, benign odontogenic tumors of an epithelial origin, accounting for approximately 1% of all oral tumors. A 40 year-old man presented with a chief complaint of a swelling over the left side of his face of 4 years' duration. On examination, gross facial asymmetry was detected, and a well-defined swelling was noted intraorally involving the left maxilla medially from the mid palatal raphe and obliterating the buccal vestibule laterally. The swelling was non-tender and exhibited dual consistencies: firm in the palate and cystic in the vestibular region. Computed tomography revealed a multilocular radiolucency, which involved the left maxilla, encroached into the left maxillary sinus and the nasal complex, and caused bony erosion. Early diagnosis and treatment are the key tools in managing ameloblastomas, failure of which may lead to a significant deterioration of the prognosis and an increased recurrence rate. Uncommon variants of ameloblastomas have been gaining interest recently. To date, 25 cases of hybrid ameloblastomas have been documented in the scientific literature. We present an extremely rare hybrid type of the ameloblastoma with combined follicular, cystic, acanthomatous, and desmoplastic variants, which render it the first of its kind to have ever been reported. PMID- 27365558 TI - Preoperative Emboli in a Pregnant Woman with Myxoma. AB - The left atrium is the most common location of myxomas, which are benign tumors. Only a few cases of myxomas in pregnancies have been reported. Our thorough medical literature search showed only 17 reported cases in the course of pregnancy. Myxomas during pregnancy and in the preterm period constitute a serious phenomenon that can mimic an early sign of a life-threatening pathology like severe mitral stenosis. We describe a 33-year-old woman, who presented with acute dyspnea to a gynecology center and was referred to our hospital for further evaluation of pulmonary embolism. Transthoracic echocardiography showed a huge left atrial myxoma, and computed tomography scan illustrated paradoxical pulmonary embolism in the left upper lung lobe via a large patent foramen ovale. The tumor required urgent cardiac surgery. In this article, we review causes of dyspnea in pregnancy and the cardiovascular effects of myxomas in pregnancy. We also describe the pathophysiological effects of cardiopulmonary bypass on the mother, fetus, and the feto-placental system during open-heart surgery. We performed a successful surgical resection of a myxoma in a pregnant woman. Given the rarity of such cases, individual multidisciplinary assessment and management strategies are essential. PMID- 27365559 TI - An Aortoenteric Fistula Arising after Endovascular Management of a Mycotic Abdominal Aortic Aneurysm Complicated with a Psoas Abscess. AB - Mycotic aortic aneurysms account for 1-3% of all aortic aneurysms. The management of this disease is controversial. Since open surgical repair is associated with high morbidity and mortality rates, endovascular aneurysm repair is an alternative treatment method with promising early and midterm outcomes, although its long-term durability is unknown. Secondary aortoenteric fistulas may occur iatrogenically after either aortic reconstructive surgery or endovascular repair. As the number of aneurysms managed with endovascular aneurysm repair has substantially increased, cases of aortoenteric fistulas referred for endovascular repair are augmented. We report the case of an aortoduodenal fistula manifested with duodenal perforation after staged endovascular and surgical treatment of a mycotic aortic aneurysm. PMID- 27365560 TI - Superior Vena Cava Syndrome due to Thrombosis: A Rare Paraneoplastic Presentation of Bronchogenic Carcinoma. AB - Superior vena cava (SVC) syndrome is not an uncommon occurrence in patients with malignancy and it is often described as a medical emergency. In majority of the cases, SVC syndrome occurs due to mechanical obstruction of the SVC by extraluminal compression with primary intrathoracic malignancies. However, intraluminal obstruction due to thrombosis can also produce symptoms and signs of SVC syndrome. Clot-related SVC obstruction is mostly associated with indwelling central venous catheter and pacemaker leads, although such thrombosis can occur spontaneously in a background of a hypercoagulable state, e.g., malignancy. Here, an unusual case of sudden onset SVC syndrome has been reported, which on initial radiologic evaluation was found to have a lung nodule without any significant mediastinal mass or adenopathy compressing SVC. Subsequent investigation with Doppler ultrasonography of the neck showed thrombosis in the right internal jugular, right subclavian and right brachiocephalic vein, which was responsible for SVC syndrome. Histopathological evaluation of lung nodule confirmed presence of an adenocarcinoma. Therefore, venous thromboembolism as a paraneoplastic syndrome should be kept in mind while evaluating a case of SVC obstruction in a cancer patient. Management of the underlying disease is of prime importance in such cases and anticoagulation is the mainstay of therapy. Ability to identify paraneoplastic syndrome may have a significant effect on clinical outcome, ranging from early diagnosis to improved quality of life of the patient. PMID- 27365561 TI - A Rare Complication with the Concomitant use of Warfarin and Nonsteroidal Anti Inflammatory Drugs: Hemoperitoneum and Intramural Small Bowel Hematoma. PMID- 27365562 TI - Recurrent Acute Pancreatitis: A Diagnostic Clue to Primary Hyperparathyroidism. PMID- 27365563 TI - 'Software and Scholarship' - Editorial. PMID- 27365564 TI - Trusting Others to 'Do the Math'. AB - Researchers effectively trust the work of others anytime they use software tools or custom software. In this article I explore this notion of trusting others, using Digital Humanities as a focus, and drawing on my own experience. Software is inherently flawed and limited, so when its use in scholarship demands better practices and terminology, to review research software and describe development processes. It is also important to make research software engineers and their work more visible, both for the purposes of review and credit. PMID- 27365565 TI - Imagining the Unimaginable: Parricide in Early Modern England and Wales, c.1600 c.1760. AB - This article explores the ways in which parricide was comprehended in England and Wales, c.1600-1760, and shows that while some parallels exist with modern explanatory models of parricide offenders, they had very different meanings in the early modern context. While both lunacy and the cruelty of parents were understood as possible contexts for parricide, neither were common. The dominant explanation was the gratuitous violence of a selfish individual who lacked compassion and who saw the parent as an obstacle-to an inheritance, riches, marriage, and freedom-to be removed. The article explores these three categories and suggests ways in which this began to change in the mid-eighteenth century. PMID- 27365566 TI - ROLE OF SURGICAL MANAGEMENT IN INJURIES OF THORACOLUMBAR SPINE. PMID- 27365567 TI - STABILIZATION OF THORACOLUMBAR SPINAL INJURIES. AB - Spinal Cord injury cases are being managed in Base Hospital Delhi Cantt since Oct. 97. 27 cases of thoracolumbar injuries were admitted in this hospital during the period Oct 97 to Aug 99. 20 patients underwent surgical treatment (9 thoracic and 11 lumbar) and 7 were treated conservatively. All these operations were done within 3 weeks following trauma, and methylprednisolone therapy was instituted in those who reached the hospital early. Contraindications to surgery included stable fracture, bed sores, any focus of sepsis and generalized bone disorders. Transpedicular fixation with Dyna-lok system was done in 10 cases, universal spinal system was applied in 6 cases and Harrington instrumentation was carried out in 4 cases. Decompression laminectomy was done in all cases. Patients with incomplete cord injury showed neurological improvement and early rehabilitation was possible after surgery. PMID- 27365568 TI - HEIGHT AND WEIGHT PATTERNS AS INDICATORS OF GROWTH AMONG SCHOOL CHILDREN IN AN AIR FORCE STATION : A CROSS-SECTIONAL STUDY. AB - A cross sectional study of school children between 6-17 years of age was carried out in an Air Force Station to determine their growth patterns as indicated by weight and height with a view to detect gender bias, if any, and compare the findings with those of affluent Indian children and National Centre for Health Statistics (NCHS), USA, standards. A total of 763 boys and 605 girls were examined. There was no gender bias in growth. Though the children compared almost favourably, with affluent Indian children, particularly in respect to stature, they were lagging far behind the NCHS standard. Goal for achieving the NCHS standards in the long run has been discussed. PMID- 27365569 TI - DNA AMPLIFICATION OF A REPETITIVE SEQUENCE - IS 6110 IN THE EARLY DIAGNOSIS OF EXTRA PULMONARY TUBERCULOSIS. AB - DNA amplification by Polymerase Chain Reaction (PCR) of a repetitive sequence specific for Mycobacterium tuberculosis, from clinical samples of extra pulmonary origin were evaluated. The 123 base pair fragment of the insertion element IS 6110 in Mycobacterium tuberculosis was amplified. A total of 50 samples were analysed by PCR and compared with culture on Lowenstein-Jensen medium (LJ) and the clinical findings of the patient. Out of the total 26 samples were positive by PCR, while only seven grew the bacilli in culture. 24 samples were negative by PCR and culture. All the seven samples that grew the bacilli on culture were positive by PCR. In remaining 19 cases that were positive by PCR but did not grow the bacilli clinical features, radiological findings and Mantoux test were strongly suggestive of M. tuberculosis. All the amplification negative cases had no positive evidence of tuberculosis but were being followed up. When correlated with culture and clinical history the sensitivity of PCR for the diagnosis of active tuberculosis was 100%. However, the specifity was only 55.8% as culture on LJ (Gold Standard) was positive in only 7 samples out of 26 samples that were positive by PCR. PMID- 27365570 TI - PENETRATING KERATOPLASTY IN HIGH RISK CASES. AB - Penetrating Keratoplasty in high risk cases like paediatric patients, complicated cases of pseudophakic bullous keratopathy, or in patients with highly vascularized corneal opacities have been a challenge for opthalmologists because of the poor outcome. 101 patients with such high risk indications underwent penetrating keratoplasty. Some of them also underwent concurrent procedures like PC IOL implantation or vitrectomy. The patients' follow up period ranged from six months to four years. The results were evaluated. Good quality donor material, good intraoperative tissue handling, aggressive and meticulous postoperative management contributed to gratifying results. However chemical injuries and patients with dry eyes continued to have a bad prognosis and keratoplasty in these cases proved to be unrewarding. PMID- 27365571 TI - AN EPIDEMIC OF PLEURISY AMONGST MILITARY RECRUITS. AB - An epidemic amongst recruits who presented with acute viral exudative pleural effusion with lymphocytic pleocytosis is analysed. Histologic and bacteriologic proof of tuberculosis was lacking in majority. Most of them recovered without pleural thickening. Overcrowding, inadequate clothing protection, stress and strain of vigorous recruit training could be important precipitating factors. None reported with parenchymal tuberculosis in two year follow up. PMID- 27365572 TI - BABY FRIENDLY HOSPITAL INITIATIVE EXPERIENCES FROM A SERVICE HOSPITAL. AB - All pregnant mothers attending antenatal clinic, mothers delivering at Command Hospital (Air Force) and parents of infants attending immunization clinic at Command Hospital (Air Force) from the period June 1998 to July 1999 are included in this retrospective and prospective cross sectional study. A preformatted questionnaire was designed to assess the practices related to breast feeding during antenatal, in labour room and postnatal ward both for the period pre BFHIand post BFH1 Programme initiated at Command Hospital (Air Force). 225 mothers were included in the study with 90 belonging to pre BFHI group (A) and 135 to post BFHI group (B). Significant changes in the breast feeding practices including antenatal advice on breast feeding and breast examination in group A & B were observed (22.3% vs 82.9% and 13.3% vs 74.8%), rooming in with mother and first feed within 1/2 hr (64.4% vs 92.5% and 35.5% vs 96.5%), teaching skill of breast feeding and manual expression (55.5% vs 91.8% vs 24.4% vs 74.0%). Other important changes included total discontinuation of formula feeds, exclusive breast milk in all preterm infants and avoiding all forms of prelacteal feeds. This study strengthens the fact that appropriate education and training of health care givers can result in reversing practices which are 'inappropriately baby friendly' to become 'appropriately baby and mother friendly'. Command Hospital (Air Force) happens to be first service hospital to be recognized as baby friendly. The experience could be applied to achieve the target of all service hospitals becoming baby friendly. PMID- 27365573 TI - DENTAL CARIES AND PERIODONTAL DISORDERS IN CHRONIC LIVER DISEASE. AB - Bacterial infections are frequent complications in patients with chronic liver disease (CLD). A potential source of infection may be dental foci. This study was carried out to assess the association of CLD with dental caries and periodontal disease. Dental caries and periodontal examinations were performed prospectively in patients with CLD (group A) and controls without any liver disease (group B). Similar examination was also carried out in alcoholics without liver disease (group C) as well as in cases with portal hypertension but no liver disease (group D) i.e. patients with Non Cirrhotic Portal Fibrosis and Extrahepatic portal obstruction. A total of 231 subjects (Group A:83, group B: 75, group C:46 and group D:27) were studied. Group A included 32 cases with chronic hepatitis B&C, 26 with alcoholic cirrhosis, 14 with postnecrotic cirrhosis, and 11 with cryptogenic cirrhosis. Measures of oral hygiene (p < 0.01), dental care (p < 0.001), and periodontal parameters were worse and the number of teeth requiring treatment (p < 0.05) was higher in alcoholics with or without cirrhosis than in healthy subjects and nonalcoholic patients with cirrhosis. Alcoholics had a lower, total number of teeth than patients without alcohol abuse and healthy controls (p < 0.01). The dental caries and periodontal status of patients with nonalcoholic cirrhosis did not differ significantly from group B. The severity and duration of liver disease had no influence on dental caries and periodontal disease. The presence of chronic alcohol abuse rather than cirrhosis or portal hypertension is a major predisposing factor for dental caries and periodontal diseases. In alcoholics, these diseases appear to be caused primarily by bad oral hygiene and poor dental care. PMID- 27365574 TI - POST OPERATIVE PAIN RELIEF IN CAESAREAN SECTION. AB - Eighty female patients in the age group of 20-40 years, weighing 40 +/- 15 Kg, in ASA physical status I and II, awaiting either elective or emergency caesarean delivery were selected for this study. Patients with cardiovascular disorders and those with significant systemic ailments were excluded from the study. They were randomly divided into two equal groups of 40 patients each. Group I was subdivided randomly into two equal sub-groups (1A and 1B) of 20 patients each and was selected for administration of epidural narcotics. Patients in sub-group 1A were given epidural morphine in the dose of 3-5 mg and those in subgroup 1B were given buprenorphine in the dose of 0.1-0.15 mg. Group II consisting of 40 patients, were again subdivided randomly into two equal subgroups (2A and 2B) of 20 patients each and were selected for administration of parenteral (intravenous) narcotics. Patients in subgroup 2A were given morphine in the dose of 5-7.5 mg I.V., and those in subgroup 2B were given 0.15-0.3 mg of buprenorphine intravenously. The degree of pain relief was assessed by applying numerical rating scale (NRS) and resulting complications were observed and recorded. It was found that 60-80% of patients with epidural narcotics, with various dosage schedules, experienced good to excellent analgesia as compared to 30-40% of patients with parenteral use of narcotics. PMID- 27365575 TI - AUDIT OF BLOOD REQUISITION. AB - A total of 2793 requisition forms received by the blood banks of a Service zonal hospital, between June 1995 and December 1999, were analysed. 1697 (60.71%) forms were demand for single unit blood. Blood was collected against only 1099 forms (39.34%) out of which 713 (64.88%) were single unit issue. Urgency of requirement and blood group of patients was omitted in 56% cases. 104 forms were received without mention of the indications for transfusion. History of previous transfusion and pregnancy/HDN were omitted in 25.1% and 37.38% cases respectively. At an average 14.61% of the total collection was discarded. Of the 292 units discarded, 242 units were due to non utilisation. A transfusion committee should be established in all hospitals with a licensed blood bank. It should constitute definite objectives and conduct regular audits (prospective audit, concurrent review or retrospective review), in order to achieve utmost efficiency and numerous benefits, in terms of workload, cost, errors, risks of transfusion and ultimately increased customer satisfaction. It should strive to abolish single unit and inappropriate transfusion, and advocate autologous transfusion. PMID- 27365576 TI - HARTMANN'S PROCEDURE REVISITED. AB - Between July 1991 and June 1999 out of 176 patients undergoing colonic surgery (elective and emergency), Hartmann's procedure was performed in 63. There were 39 males and 24 females. Mean age was 43 years (range 12 to 81). To assess the utility of Hartmann's procedure the documents of all these 63 patients were retrospectively analysed. In 47 bowel continuity was reestablished. The over all mortality in first stage operation (Hartmann's procedure) was 12.7% and mortality in the second stage procedure (reestablishing bowel continuity) was nil. Complication rate was drastically less in second operation. The authors conclude that Hartmann's procedure is safe and effective while dealing with colorectal pathologies as resection and primary anastomosis is fraught with danger. PMID- 27365577 TI - SHORT BOWEL SYNDROME IN CHILDREN. AB - Short bowel syndrome, a devastating outcome after major intestinal resection, manifests as malabsorption and diarrhoea. Improved outcome in recent years has come about with better understanding of the disease and its sequelae. Medical therapy using H2 receptor antagonists, loperamide and growth hormone analogues has been found useful. Total parenteral nutrition has revolutionized the outcome of this crippling disorder. Diverse spectrums of surgical procedures aimed at deceleration of intestinal transit and intestinal lengthening have not found favour in clinical practice. Intestinal transplantation remains the only viable option when intestinal adaptation is inadequate and complications of total parenteral nutrition ensue. PMID- 27365578 TI - VIAGRA : IS IT A WONDER DRUG ? AB - Male erectile dysfunction is common and frustrating after the age of forty years. Erectile dysfunction is a cause of misery, relationship difficulties, and significantly reduced quality of life. Sildenafil citrate (Viagra) has shown promising results in recently published clinical trials. Sildenafil is a potent and competitive inhibitor of cGMp specific phosphodiesterase-5, predominant isoenzyme in the human corpus cavernosum. It is effective in erectile dysfunction of diverse origin, however it requires a patent vascular system to be effective. It is not effective in patients with endocrinal impotence, loss of libido, premature ejaculation or infertility. Its main adverse effects are headache, flushing, dyspepsia, diarrhoea, nasal congestion, indigestion, visual disturbances, dizziness and rash. Ventricular tachycardia and acute myocardial infraction have been reported in patients of ischaemic heart disease after consumption of sildenafil. Six deaths have been reported in patients taking nitrates. In India it is likely to be prescribed by a primary care physician without complete evaluation of patient on complaint of impotence. Hence the ethical question of who should prescribe this drug should be addressed by medical fraternity and proper guidelines formulated to avoid misuse of sildenafil. Phosphodiesterase is distributed in nerve, central nervous system, and systemic vasculature, hence long-term effects of drug on these tissues has to be ascertained. It should be made mandatory to report all adverse drug reactions to ADR monitoring centres. It is a wonder for those who require it, but has potentially dangerous adverse effects and drug interactions and hence is and not a wonder pill for all kinds of impotence. PMID- 27365579 TI - PHARMACOLOGICAL THERAPY OF ERECTILE DYSFUNCTION. PMID- 27365580 TI - FOR WHOM DO WE TOIL? AB - Indoor workload of a zonal service hospital for one month was studied. Service personnel and their dependents form the bulk of workload. Though the absolute number of ex-servicemen and their dependents is small, the resources spent on them are quite high. The average stay in hospital is 15 days. Rapid turnover of the patients reveals appropriate utilization of resources. Optimization of resources is possible by reducing the number of admissions for administrative purposes. PMID- 27365581 TI - CONGENITAL ANOMALY PRESENTING AS LUMP ABDOMEN IN ADOLESCENT GIRL. PMID- 27365582 TI - NASAL ANGIOFIBROMA : An Unusual Presentation. PMID- 27365583 TI - RECURRENT RETROPERITONEAL HYDATIDOSIS. PMID- 27365584 TI - MALAKOPLAKIA OF LUNG IN AN IMMUNOCOMPROMISED PATIENT. PMID- 27365585 TI - TRIPLETS - A Rare Case Report. PMID- 27365586 TI - ENDOBRONCHIAL TUBERCUCLOSIS PRESENTING AS A BRONCHOCELE. PMID- 27365587 TI - INTERNAL JUGULAR PHLEBECTASIA. PMID- 27365588 TI - A CASE OF FACIAL DIPLEGIA. PMID- 27365589 TI - CRANIOSYNOSTOSIS : MANAGEMENT IN INFANCY. PMID- 27365590 TI - REGIONAL BLOCKS IN EXTREMITY TRAUMA. PMID- 27365591 TI - AEROBIC PYOGENIC LIVER ABSCESS. PMID- 27365592 TI - ANOREXIA NERVOSA : A CAUCASIAN SYNDROME RARE IN ASIA. PMID- 27365593 TI - INTERMEDIATE UVEITIS PARS PLANITIS. PMID- 27365594 TI - INCIDENCE AND ETIOLOGY OF RESPIRATORY DISTRESS IN NEWBORN. PMID- 27365595 TI - CONGENITAL TORTICOLLIS: Reply. PMID- 27365596 TI - CONGENITAL TORTICOLLIS. PMID- 27365598 TI - INCIDENCE AND ETIOLOGY OF RESPIRATORY DISTRESS IN NEWBORN: Reply. PMID- 27365597 TI - DESIGN MODIFICATION OF THE BACKREST OF HOSPITAL BEDS IN THE ARMED FORCES : A PROPOSAL. PMID- 27365599 TI - MALARIA - DIAGNOSTICS TODAY. PMID- 27365600 TI - IMMUNOCHROMATOGRAPHIC TEST: A NEW DIMENSION IN DIAGNOSIS OF PLASMODIUM FALCIPARUM MALARIA. AB - 75 patients with clinical features suggestive of malaria were studied to evaluate the efficacy of immunochromatographic test (ICT), which detects histidine rich protein-2 antigen secreted by Plasmodium falciparum (Pfhrp-2), as against direct microscopy. There were 40 cases of P falciparum malaria, 14 cases of P vivax malaria and 21 cases of non-malarial fevers. Direct microscopy could detect 27(67.5%) P falciparum cases but failed to detect 13 cases (32.5%) whereas ICT could detect 35(87.5%) P falciparum cases out of 40 but failed to detect 5(12.5%) cases. All the P vivax cases and non-malarial fever cases were negative for ICT. The sensitivity and specificity of ICT is 87.5% and 100% respectively where as the positive predictive value and the negative predictive value of the test is 100% and 87.5% respectively. It is concluded that ICT test is a good adjunct to blood smear studies in fever cases with neurological and multiorgan dysfunction and in antenatal ladies. PMID- 27365601 TI - EPIDEMIOLOGICAL AND ENTOMOLOGICAL CORRELATION OF MALARIA TRANSMISSION IN AN AIR FORCE STATION. AB - An epidemio-entomological study was carried out at an Air Force Station located in a semi-hilly, forested, highly malarious, tribal belt in Central India. Malaria incidence for the period 1995-1998 showed highest incidence among DSC personnel. Entomological studies identified exophilic vectors (A culicifacies), whose bionomics coincided with outdoor nature of occupation of the DSC personnel. Active surveillance among neighbouring villages showed high endemicity particularly in the tribal villages. Heavy rainfall in 1997 had a slight inhibiting effect on transmission. Because of exophilism of the vectors and occupational hazard of malaria faced by the DSC personnel, personal protective measures hold the key to malaria control in this group. PMID- 27365602 TI - COMPARISON OF RAPID METHOD OF DNA EXTRACTION USING MICROWAVE IRRADIATION WITH CONVENTIONAL PHENOL CHLOROFORM TECHNIQUE FOR USE IN MULTIPLEX PCR FOR mec A AND fem B GENES TO IDENTIFY GENOTYPES OF MRSA FROM CULTURES. AB - Methicillin Resistant Staphylococcus aureus (MRSA) infection is a major cause of morbidity and mortality in hospitalised patients and requires vancomycin for effective therapy. Rapid identification of MRSA is vital to control MRSA outbreaks in hospitals. Identification of MRSA is a time consuming process requiring more than 48 hours and is labour intensive involving culture, biochemical tests and antimicrobial susceptibility testing. In this study we have used microwave irradiation of the bacterium obtained from cultures which was then directly subjected to a multiplex PCR technique to accurately and rapidly identify the presence of mec A and fem B genes which characterise MRSA. This has been compared with the standard method of lysing the bacterium and DNA extraction using phenol chloroform method followed by multiplex PCR. The microwave lysis method followed by direct PCR has been found to be less time consuming, 5 hours, as compared to 9 hours by conventional technique. Use of this strategy would enable early identification and early implementation of control measures. PMID- 27365603 TI - TO STUDY INCIDENCE OF CHLAMYDIAL GENITAL TRACT INFECTIONS USING ENZYME IMMUNO ASSAY-ANTIGEN DETECTION AND CELL CULTURE METHODS. AB - Endocervical swabs from 315 patients were screened for chlamydial infection by using Enzyme Immuno Assay technique for antigen detection. Of these, 190 patients were of infertility and 125 patients were with history suggestive of pelvic inflammatory disease (PID). 100 age matched controls were also screened for the detection of chlamydial antigen by using EIA. The overall incidence of chlamydial infection in this study group was 15.2%. 21 (11.05%) of the infertility patients and 27 (21.6%) of the pelvic inflammatory disease cases were found to be positive for chlamydial antigen. The prevalence rate was found to be high in the age group of 31-40 years in both study groups i.e. infertility group (14.7%) and PID group (50%). All the ELISA positive cases (48) and randomly selected (10) age matched controls were screened by tissue culture using McCoy cell line. In the tissue culture, 44 of the 48 samples were found to be positive and none of the controls groups were found positive. 4 samples showed discordant results possibly due to the presence of non-viable organism or inhibitory material present at the sample site. The sensitivity and specificity of ELISA with respect to tissue culture are 100% and 71% respectively. The positive predictive value and the negative predictive value of the ELISA are 91.6% and 100% respectively. The efficiency of the test was found to be 93.1%. PMID- 27365604 TI - COMPARISON OF MIDAZOLAM AND THIOPENTONE AS INDUCTION AGENTS IN GENERAL ANAESTHESIA. AB - A single blind parallel group study was performed in 137 patients undergoing elective surgery under general anaesthesia to compare the efficacy and tolerability of midazolam 0.15 to 0.25 mg/kg or thiopentone 6 mg/kg. Induction time was 45.0+/-17.1 secs in midazolam group in comparison to 32.0+/-9.5 secs in thiopentone group and the frequency of apnoea was 11.5% and 17.1% respectively. There was no difference in the duration of apnoea in the two groups. No venous intolerance was experienced during the study. It appears that midazolam is a suitable alternative to thiopentone and would be of value where the latter is contraindicated. PMID- 27365605 TI - TOTAL QUALITY MANAGEMENT - THE NEW PARADIGM IN HEALTH CARE MANAGEMENT. AB - Hospitals are by nature complex organisations and the complexity is compounded in service hospitals with perceived notion of service deficiencies. Quality has emerged as a major issue in health care sector and TQM has been accepted as a major long-term strategic initiative towards continuously improving quality of health care. Key concepts of TQM start with top management leadership with emphasis on process and customer focus. Implementation of TQM in service hospitals will require Quality Management awareness, training and framework development as well as development of customer awareness. TQM has been widely applied in clinical field with successful outcome. TQM is not a short-term solution, it has to be understood and practised as a long-term strategic commitment. PMID- 27365606 TI - COSTING A HOSPITAL SERVICE PRODUCT: MARGINAL Vs ABSORPTION COSTING. AB - Costing a service product is a challenging but important tool for cost control. Different methods used for costing may provide varying costs and the choice of the method used becomes important. Use of absorption costing and marginal costing method and treatment of labour cost as variable and fixed cost provided different results in the present study of the cost of below knee patellar tendon bearing prosthesis. The study shows that marginal costing should also be done along with the absorption cost as it provides better indicator for cost control. PMID- 27365607 TI - ISOLATED RADIAL NERVE INVOLVEMENT IN LEPROSY. PMID- 27365608 TI - 1% PROPOFOL IN ANAESTHESIA FOR EMERGENCY NON CARDIAC SURGERY IN HEART FAILURE: A REPORT OF TWO CASES. PMID- 27365609 TI - KIKUCHIS DISEASE. PMID- 27365610 TI - GIANT EPIDERMOID CYST OF THE FLOOR OF MOUTH. PMID- 27365611 TI - MYOCARDIAL INJURY IN ELECTRICAL BURNS. PMID- 27365612 TI - STENT IN ACUTE NON-Q WAVE MYOCARDIAL INFARCTION. PMID- 27365614 TI - HOMOLOGOUS BLOOD TRANSFUSION: DO WE HAVE ANY ALTERNATIVE? PMID- 27365613 TI - FURAZOLIDINE INDUCED ERYTHEMA MULTIFORME. PMID- 27365615 TI - HOMOLOGOUS BLOOD TRANSFUSION: DO WE HAVE ANY ALTERNATIVE?: REPLY. PMID- 27365616 TI - MITRAL STENOSIS: HAS BALLOON DILATATION REPLACED SURGERY? PMID- 27365617 TI - CHANGING PATTERN OF SEXUALLY TRANSMITTED DISEASES IN THE ARMED FORCES. PMID- 27365618 TI - NURSES IN THE OLIVE GREEN: WHAT NEXT? PMID- 27365619 TI - "DISTRACTION OSTEOGENESIS" AN EMERGING CONCEPT IN THE CORRECTION OF CRANIOFACIAL DEFORMITIES. PMID- 27365620 TI - LASER INTERVENTION IN MACULAR OEDEMA DUE TO BRANCH RETINAL VEIN OCCLUSION. AB - 20 out of 25 patients of Branch Retinal Vein Occlusion (BRVO), with macular oedema of more than six months duration and less than one year, with visual acuity (VA) less than 6/18 corrected and without retinal neovascularisation (NVE) or capillary non-perfusion (CNP) were subjected to argon-green laser photocoagulation applied in a macular grid fashion. At the end of two years 14/20 (70%) laser treated eyes in comparison to 2/5 (40%) of the non-laser group had corrected visual acuity of 6/12. PMID- 27365621 TI - MANAGEMENT OF CONGENITAL ATRESIA EAR. AB - A total of 3 out of 5 cases of major congenital ear malformation seen in out patient department in two years in 1997 and 1998 were operated for functional reconstruction of external auditory canal, middle ear and ossicular chain. 2 cases of bilateral malformation of auricle grade 2 were advised otoplastic repair prior to tympanoplasty. Out of the 3 cases operated by anterior transatretic bone approach, 2 cases had good hearing improvement in air conduction threshold of up to 30 db hearing level (averages of 0.5,1.2 and 3 khz). One case developed external canal stenosis by six months post operatively and drop in hearing. There was no facial nerve injury in any of the cases. This paper analyses the importance of facial nerve delineation preoperatively based on its embryological development and its relationship with temporal bone and membranous labyrinth. It also focuses on the various parameters like timing of surgery, importance of (CT) scanning, use of facial nerve monitor and surgical expertise and experience which govern the surgical intervention and its results in congenital ear atresia. PMID- 27365622 TI - CLINICO-RADIOGRAPHIC EVALUATION OF XENOGRAFTS IN MAXILLOFACIAL SURGERY. AB - An endeavour to find a suitable substitute for autogenous bone graft in corrections of maxillofacial deformities has been going on. Evaluation of commercially processed xenograft (SURGIBONE) has been carried out as a substitute for autogenous grafts in various maxillofacial surgical procedures in the Department of Dental Surgery at Armed Forces Medical College. Clinical and radiographic evaluation in 15 patients revealed highly satisfactory result with complete integration of the graft without any adverse host tissue reaction within the follow-up period lasting from 12-18 months. PMID- 27365623 TI - TRIBAL MALARIA AND ITS EFFECTS ON AIR FORCE STATION AMLA AND SURROUNDING AREAS : AN EPIDEMIOLOGICAL STUDY. AB - An epidemiological study on the transmission of malaria was carried out in an Air Force (AF) station located in a densely forested, highly malarious tribal belt in Central India. Among the AF station population, Defence Service Corps (DSC) personnel, whose occupation involved night patrolling in densely forested locales on the perimeter of the AF station, with the tribal villages within flight range of the vector mosquitoes, were the group most affected in terms of both overall malaria incidence and high falciparum rates. Among the neighbouring villages, the tribal villages had significantly higher rates of malaria as compared to the non tribal villages. Vector identification revealed the presence of malaria vectors Anopheles culicifacies and A fluviatilis. Heavy breeding was noted in the surrounding villages, both in natural water channels and man made projects, such as installation of village hand pumps without proper drainage. A rising trend of malaria was obvious in these villages. Incidence among the service population could be controlled to some extent by specifically targeted measures inside the camp area. Strategy for controlling malaria in such endemic pockets has been discussed. PMID- 27365624 TI - MAGNETIC RESONANCE IMAGING IN INTRACRANIAL TUBERCULOSIS. AB - Tuberculosis (TB) is still a major cause of serious illness in many parts of the world. Intracranially, TB manifests itself variably as meningitis, tuberculoma and tubercular abscess [1]. Although its appearance on MR is not absolutely specific, it is important in the proper clinical setting to recognize the range of possible patterns that can be observed on images [2]. Magnetic Resonance Imaging (MRI) has emerged as a quality imaging tool aiding in the diagnostic evaluation of intracranial TB variably displaying meningeal, parenchymal, osseous and craniovertebral lesions. The MRI characteristics of 18 cases of intracranial TB were reviewed. RESULTS: Multiple lesions occured with a slightly higher incidence at 61%. In all, 11 patients (61%) presented with meningitis. Meningeal lesions without parenchymal or vascular involvement were seen in 16% of cases. 2 patients had extension of enhancing exudates into the spinal subarachnoid spaces. While 6 patients had focal intra-axial tuberculomas, representing 33% cases, 3 patients presented with infarcts. 1 patient presented with haemorrhagic infarct at right middle cerebral artery territory while two other showed multiple small infarcts. Hydrocephalus was identified in 4 patients and epidural lesions were noted in 2 cases. MRI should be considered as the imaging modality of choice for patients with suspected intracranial TB. PMID- 27365625 TI - SEROLOGICAL DIAGNOSIS OF TOXOPLASMA GONDII INFECTION IN VARIOUS PATIENT POPULATION IN THE ARMED FORCES. AB - The study included 200 healthy age and sex matched controls (120 healthy volunteers and 80 healthy antenatal cases without any bad obstetric history) and 300 cases comprising patients with bad obstetric history (BOH) 80 cases, seizure or encephalitis 50 cases, cervical lymphadenopathy 30 cases, congenital deformity 30 cases, HIV infected 80 cases and patients on long term immunosuppression 30 cases. Anti-toxoplasma IgG & IgM were measured by ELISA and individuals found positive for anti Toxoplasma gondii IgM or with high titre of IgG were subjected to repeat testing after 3 weeks for rise in titre. True sero-prevalence of T gondii infection was found to be 19% and it increased with increasing age in the population. 2.33% patients were found to have acute toxoplasma infection. Statistical significance was seen only in patients with BOH and children born with congenital abnormality. PMID- 27365626 TI - EXPERIENCE FROM A COMMUNITY PSYCHIATRIC EDUCATION VENTURE IN THE NAVY. AB - Naval Headquarters had directed the psychiatrists in the three commands of the Navy to conduct a series of lectures followed by question-answer sessions to the divisional officers and senior sailors. The purported reason was to reduce the incidence of various psychiatric illnesses, drug abuse, alcoholism and suicide among service personnel and their families. A power point presentation was prepared and six interactive sessions conducted with divisional officers and senior sailors. The logic followed in the preparation of the presentation is explained. The audience was requested to fill in a questionnaire to evaluate their demographic profile, their understanding and attitude to psychiatry and efficacy and their suggestions to improve upon the current presentation. Psychiatric awareness among the targeted population was low but receptivity to the presentation was enthusiastic. This effort is preliminary and further studies are called for in this important field of health education. PMID- 27365627 TI - INGUINAL HERNIA IN FEMALES. AB - 9 patients of inguinal hernia in females were diagnosed in a total of 50 patients who presented with congenital groin problems, 8 of these were managed surgically. There were 6 small children, 1 young girl and 2 elderly ladies. All children were managed by herniotomy and herniorrhaphy was done in women. 2 patients under one year presented with irreducible hernia, one of them on exploration was found to be having sliding hernia with incarcerated ovary and tube as contents while other one had incarcerated loop of small intestine. Contents were reduced in both the patients after division of external ring as there was no sign of strangulation. One of our patients never turned up for surgery. All the operated patients were asymptomatic during the follow up period of 6 months to one year with no recurrence or wound infection. None presented on the contralateral side on follow up. Repair of inguinal hernia in females should be carried out at the earliest after a diagnosis is made, because incarceration occurs more frequently in the first year of life, as seen in this study. PMID- 27365628 TI - ACUTE RESPIRATORY INFECTION AMONG CHILDREN IN AN AIR FORCE COMMUNITY. AB - 984 children of 745 families were studied for occurrence of Acute Respiratory Infection (ARI). Incidence of ARI was 3.5 episodes per year among infants and 1.8 episodes per child per year among under-five children. 88.8% episodes of ARI were mild while 11.2% episodes were moderate to severe, which mostly occurred in winter. Parental smoking habit, decline in duration of breast feeding, bedroom smoke pollution and over crowding were found to increase the risk of ARI among children. An effective preventive strategy has been highlighted. PMID- 27365629 TI - A STUDY OF HYPERINSULINAEMIA AND DYSLIPIDAEMIA IN HYPERTENSIVE PATIENTS OF ARMED FORCES. AB - All patients attending the outpatient department were screened for hypertension. An attempt was made to correlate presence of hyperinsulinaemia (HI), dyslipidaemia and anthropometric characteristics in these hypertensives. Effect of angiotensin converting enzyme inhibitor (ACEI) and beta blockers on serum insulin was also studied. 85 patients with blood pressure (BP) >= 160/90 mm Hg and 94 controls with a BP of < 130/85 mm Hg were studied. All underwent clinical examination, anthropometric measurements (body mass index (BMI), waist hip ratio (WHR), skin fold thickness (SFT) and laboratory investigation (serum insulin, glucose, lipid profile) and post oral glucose load (POGL) for insulin and glucose. Serum insulin was estimated by I(125) radio immuno assay. Patients were randomly divided into group A (Tab enalapril) and group B (Tab atenolol). In 51 patients who completed the study, fasting and POGL insulin and fasting lipid profile were estimated two months after treatment. Mean age of cases was 38.91 years. 50% of patients had stage II hypertension. BMI was increased in 36 cases (42.35%) as compared to 9 in (9.57%) controls. Increased WHR was found in 40 cases as compared to 26 in controls. The SFT was more in cases compared to controls. 47 (55.29%) of 85 cases had abnormal lipid profile as compared to 25 (26.60%) in 94 controls. The fasting and POGL insulin levels (13.85 and 60.05 micro u/ml respectively) in cases were significantly higher than in controls (6.87 and 16.16 micro u/ml respectively). The mean POGL insulin values were much higher in obese compared to non-obese hypertensives. The decrease in mean fasting and POGL insulin values in patients taking ACEI and beta blockers were similar. Abnormal lipid profile was significantly more in cases than controls. Increased total cholesterol (TC), Low density lipoprotein cholesterol (LDLC) and total cholesterol (TC)/high density lipoprotein (HDL) ratio were the most frequent abnormality. The mean insulin (both fasting and POGL) levels were higher in obese hypertensives and those with abnormal lipid profile. Both drugs had equal efficacy in reducing the insulin values. PMID- 27365630 TI - MANAGEMENT OF CEREBRAL MALARIA IN THE YEAR 2001. PMID- 27365631 TI - CURRENT STATUS OF DISULFIRAM THERAPY. AB - The effectiveness of disulfiram is linked to the disulfiram-ethanol reaction in the treatment of Alcohol Dependence Syndrome. However disulfiram therapy is associated with various adverse effects and needs a structured and supervised after care program. Relapse rate is very high once disulfiram therapy is discontinued. Keeping these factors in mind disulfiram therapy is used less often today than previously. PMID- 27365632 TI - HEALTH AND PERFORMANCE OF MILITARY PERSONNEL IN COLD CLIMATIC ENVIRONMENT OF THE WESTERN HIMALAYAS. AB - Indian Armed Forces are constrained to deploy a large number of troops in the western Himalayas in the interest of national security and territorial integrity. The region represents extremely rugged, arid and cold climatic conditions. The altitude ranges from 8000 to 23000 feet with winter temperatures ranging from -35 degrees C to - 55 degrees C in some regions. Low environmental humidity, hypo baric hypoxia and high solar ultra-violet radiation with its attendant problems further compound the hardships faced by the troops in these climatic conditions. The role of the Armed Forces medical personnel is extremely challenging, as they have to ensure maintenance of health and physical fitness of the troops to ensure optimal performance during peace and during operations. These considerations include nutrition, physical fitness programmes suitable for the terrain and climatic conditions, protection against cold and hypoxia induced health problems, clothing and shelter taking into consideration the ergonomic factors, human waste disposal and prompt medical attention and evacuation in case of illness. An overview of the effects of cold hypoxic environment on health and performance of Indian troops, measures employed by the Armed Forces to maintain health of troops including psychological factors and the incidence of various cold induced health problems during peace time compared to operational period over the last 10 years is presented in this paper. PMID- 27365633 TI - TO ERR IS HUMAN, NEGLIGENCE IS SIN. AB - There is often a fine line between medical malpractice and wrong doing. Physicians need to develop techniques and skills that enhance the patient physician relationship and promote clientele satisfaction based on honesty and prudency. Proficiency of writing prescriptions accurately and fluently requires practice. Failure to follow programmes which maintain the integrity of patients' records often has negative influence. PMID- 27365634 TI - AN IMPROVISED ORAL MUCUS EXTRACTOR FOR NEONATES A SIMPLE LOW COSTING METHOD. PMID- 27365635 TI - TUBERCULOSIS OF STERNUM. PMID- 27365636 TI - ODONTOAMELOBLASTOMA : A RARE ODONTOGENIC TUMOUR. PMID- 27365637 TI - KLEINE LEVIN SYNDROME. PMID- 27365638 TI - FRONTAL MUCOCELE AS A CAUSE OF GROSS UNILATERAL PROPTOSIS. PMID- 27365639 TI - BONDED RAPID PALATAL EXPANSION AN IMPORTANT ADJUVANT IN MULTIPHASIC ORTHODONTIC THERAPY. PMID- 27365641 TI - SELF PROCUREMENT OF DRUGS. PMID- 27365640 TI - AN UNUSUAL CAUSE OF EPISTAXIS. PMID- 27365642 TI - DAILY COST OF MEDICINES ISSUED TO PATIENTS IN A MEDICAL INSTITUTION. PMID- 27365643 TI - PROBLEM OF NON DEFLATABLE FOLEY'S CATHETER BALLOON. PMID- 27365644 TI - NECROTIZING FASCITIS. PMID- 27365645 TI - NECROTIZING FASCITIS: Reply. PMID- 27365646 TI - CRUSH SYNDROME REVISITED. PMID- 27365647 TI - SURGEON AND HIV INFECTION, POST EXPOSURE PROPHYLAXIS: NEED OF THE HOUR. PMID- 27365648 TI - DOPPLER ULTRASOUND. PMID- 27365649 TI - DELTAMETHRIN IMPREGNATED MOSQUITO NETS : AN EXPERIMENTAL STUDY IN AN AIR FORCE STATION IN CENTRAL INDIA (DELTAMETHRIN TRIAL). AB - An experimental study was carried out to determine the efficacy of deltamethrin impregnated mosquito nets in reducing malaria incidence under field conditions in an Air Force Station. Out of the total study population of 748 airmen and DSC personnel, 320 got their mosquito nets impregnated with deltamethrin, while 428 used unimpregnated mosquito nets. During the three months observation period, there was no significant difference in malaria incidence among the two groups (Yates Chi Sq=0.05, p=0.829405, Relative risk = 0.96 with 95% CI between 031 and 2.98). In view of study findings, it was concluded that in the station, use of deltamethrin impregnated mosquito nets will not reduce incidence of malaria appreciably, the stress has to be on outdoor personal protective measures. PMID- 27365650 TI - A COMPARATIVE STUDY OF CHEST RADIOGRAPHIC FEATURES BETWEEN HIV SEROPOSITIVE AND HIV SERONEGATIVE PATIENTS OF PULMONARY TUBERCULOSIS. AB - Chest radiographic appearance of pulmonary tuberculosis (TB) in Human Immunodeficiency Virus (HIV) positive patients was reviewed. A study group of 50 HIV +ve cases and a control group of 100 HIV -ve cases were analysed. The chest radiographs of HIV seropositive group showed significantly higher incidence of thoracic lymphadenopathy (36% vs 8%, P<.001), pleural effusion (28% vs 10%, P<.01) and miliary pattern (12% vs 2%, P<.05) as compared to the seronegative group. Cavitation was less common in the seropositive group (8% vs 35%, P<.001) than the seronegative group. Upper zone involvement was significantly less common in the study group (38% vs 77%, P<.001) as compared to the control group. PMID- 27365651 TI - NEED FOR PRECISE PROTOCOL IN MAGNETIC RESONANCE IMAGING OF THE POST OPERATIVE SPINE. AB - Gadolinium enhanced Magnetic Resonance Imaging (MRI) for the evaluation of the post operative lumbo-sacral spine is a sensitive and specific imaging technique. A need for establishing a specific protocol for Failed Back Surgery Syndrome (FBSS) for use in the service hospitals is highlighted for convenience of patient management and preservation of active manpower. The MR scan of 50 patients performed over a span of six months, who complained of persistent low backache even after surgery, were retrospectively analysed. The specificity of this series using MRI in indicating the exact cause of FBSS was clocked at only 30%. The conditions diagnosed were rectifiable. The balance of the patients who could not be offered any specific diagnosis towards the cause, were being managed conservatively / placed in low medical category for a considerable period. It was noted with concern that there was non prevalence of sequence like the fast spin echo with gadolinium enhancement as a routine. PMID- 27365652 TI - DIAGNOSING DISSEMINATED INTRAVASCULAR COAGULATION IN ACUTE INFECTION : CAN WE DO WITHOUT FDP & D-DIMER. AB - Alterations in coagulation profile viz. platelet count, prothrombin time (PT), partial thromboplastin time with kaolin (PTTK), thrombin time (TT) and fibrinogen were studied in 96 patients (73 males and 23 females) of acute infections. Fibrin/fibrinogen degradation products (FDP) level >25ug fibrinogen equivalent unit (FEU)/ml along-with D-dimer >1.0ug FEU/ml was considered criteria for diagnosis of disseminated intravascular coagulation (DIC). Normal values were established using plasma from 12 healthy voluntary blood donors. Out of these 96 patients, 15 had infection with Gram positive bacteria, 23 with Gram negative bacteria and 38 with Dengue. In 20 patients, nature of infection was not defined. Mean platelet count per cubic millimetre was 2.14 lac in Gram positive infection and 1.74 lac in Gram negative infection (p=0.07). There was no significant difference in other coagulation parameters in Gram positive and Gram negative infection. Platelet counts were low in 71% of Dengue patients but there was no significant alteration in PT, PTTK and TT. None of the Dengue patients had hypofibrinogenemia or DIC though hyperfibrinogenemia was present in 21% of Dengue patients. 20 patients had features of septicemia (Gram +ve 7, Gram -ve 8, undefined 5); 10 had concomitant DIC. DIC was present in additional 4 patients of acute infection without septicemia. PTTK was raised in 60% of the septicemia patients. 20 out of 82 non-DIC acute infection patients had subnormal PTTK. Commonest alteration in 14 DIC patients was raised PTTK with a sensitivity of 78.6% and specificity of 81.7%. Low fibrinogen levels though specific for DIC, were present in only 21.4% of the DIC patients. Combinations of PTTK >38 sec with PT >15 sec or platelet count < 1.5 lac/mmm(3) were good screening tests for DIC and detected 11 and 10 patients out of 14 with three and two false positives respectively. PMID- 27365653 TI - COMPREHENSIVE SURGICAL MANAGEMENT OF ARTHRITIC KNEE. AB - Total knee arthroplasty is not the only available surgical option for arthritic knees. It varies according to patient's age and severity of the disease. 105 arthritic knees were surgically treated at the Joint Replacement Centre of Army Hospital (R&R) in last 4 years. 77 knees were osteoarthritic and 28 were rheumatoid. 24 of these were treated by arthroscopic debridement, 7 underwent unicondylar knee replacement and 74 underwent total knee replacement using Freeman Samuelsun (F/S) or Low Contact Stress (LCS) implants. The indications, contraindications, results and complications of these procedures are discussed. PMID- 27365654 TI - COMPUTERISED TOMOGRAPHY GUIDED TRANSTHORACIC ASPIRATION BIOPSY. AB - We report our experience of 32 patients, which were subjected to Computerised tomography (CT) guided transthoracic fine needle aspiration biopsy (T-FNAB) with particular reference to technique, sensitivity and complication rate following the procedure. The biopsy aspirate was obtained either using a spinal or a Chiba needle. Pneumothorax occurred in 7 patients and transient postbiopsy haemoptysis in 2 patients. None of the patients with pneumothorax or haemoptysis required any treatment. PMID- 27365655 TI - THE CD 10 MARKER IN THE INVESTIGATION OF ACUTE LYMPHOBLASTIC LEUKAEMIA. AB - Immunophenotyping of leukaemias is presently well established. It is invaluable for proper case management [1]. The most useful information on the management of cases of Acute Lymphocytic Leukaemia (ALL) is provided by the detection of the CD 10 marker on the leukaemic cell. The CD 10 positive ALL has since long been associated with a favourable prognosis as compared to the CD 10 negative ALL [1, 2]. As immunophenotyping is resource intensive, the monoclonal antibodies (MO ABS), are not in widespread use in our country. The expenses involved make this procedure prohibitive in most institutions. For this reason, a limited panel of MO ABS has been used in this study, with a special emphasis on the CD 10 marker. A total of 25 cases of ALL were studied. 17 cases were found to be positive for the CD 10 marker (68%). These cases were associated with a favourable prognosis as compared to the CD 10 negative group. Although, the diagnosis of ALL and leukaemias in general, is essentially based on the study of Romanowsky stained smears [3, 4], the additional information provided by the cell surface marker study results in better case management [1]. PMID- 27365656 TI - DEVELOPING A COMPUTER AIDED EVALUATION TOOL TO MEASURE THE QUANTITY OF NURSING CARE, BASED ON NURSING DIAGNOSIS, FOR UNDERGRADUATE NURSING CADETS. AB - In order to find out the indicators for quality, it is necessary to define a scale, which permits us to measure the outcome of health care in relationship to the hospital activities. A descriptive survey method developmental in nature was undertaken on a purposive sample of 100 Nursing Cadets, working in the Medical Surgical Wards. The Nursing Process Approach Model was used with the objectives of first reviewing the existing system of evaluation of nursing care rendered, then a computerized evaluation tool was designed and developed in Foxpro 2.5 pogramming language and its effectiveness was tested on the student sample. Findings suggested that 57.14% of the faculty members felt that there was no standardized tool to measure the quality of the nursing care rendered in the wards. 64.29% stated the absence of set criteria for measuring quality. While 89% of the students expressed that the computerized tool directed them to render basic nursing care in a systematic manner, 70%of them expressed that competent, accountable and compassionate nursing care could be rendered using the tool. It also gave impartial evaluation of the quality of nursing care rendered based on nursing diagnosis (p<0.01). Results could serve as an initiative for ongoing research on information feedback system as well as recording action taken to keep performance in line with the standards of patient care. PMID- 27365657 TI - FINE NEEDLE ASPIRATION CYTOLOGY OF LYMPH NODES IN HIV INFECTED PATIENTS. AB - Lymphadenopathy is the commonest presentation in HIV positive individuals. Fine needle aspiration cytology of 196 HIV positive patients was studied during six monthly review. 75% paients in this study who were asymptomatic were detected to have lymphadenopathy during the surveillance. 82% had lymph nodes smaller than 1cm size. Lymphadenopathy at more than one site was observed in 46.8% cases. Commonest opportunistic infection noticed was tuberculosis (TB) in 34.2%. Cyto morphologically reactive pattern with Add fast bacilli (AFB) positivity was observed in 16.4% of TB cases. In 2.9% cases AFB were detected even in the tissue fluid. Negative images of AFB were observed in the macrophages in 3 cases. TB was detected with equal frequency in both asymptomatic and symptomatic groups. Axillary nodes pose problem due to deeper location. False positives were a case of dermatopathic lymphadenopathy and a case of Kimura's disease. False negatives include two cases of TB lymphadenitis. Pathogens should be looked for irrespective of cyto-morphology. Biopsy should be done to confirm cases of lymphomas. Fine needle aspiration cytology should be included in the protocol of six monthly review of HIV infected cases. PMID- 27365658 TI - IMPACT OF EDUCATION OF PARENTS ON NUTRITIONAL STATUS OF PRIMARY SCHOOL CHILDREN. AB - In a cross-sectional study the nutritional status of 2585 school children, including 1253 boys and 1332 girls, aged between 5 and 15 years was correlated with the levels of literacy of their parents. The study showed a direct relationship between the levels of literacy of parents and the nutritional status of children. When the same was tested separately for mothers and fathers in relation to the sex of the child, it was noted that nutritional status of boys and girls was not different irrespective of mother's literacy level. However, in case of fathers it was noticed that with the Increase in the literacy level of fathers, the nutritional status of boys was better than that of girls. PMID- 27365659 TI - MILITARY ENVIRONMENT AND FECUNDITY : A STUDY OF WOMEN IN UNIFORM. AB - Fecundity is an area where individual experiences, community belief and anecdotes cloud scientific evidence. It has been a common belief that working women experience various types of subfecundity like infertility, abortion and prolonged waiting time for pregnancy. Work environment may be contributing to this end, besides the delay in starting a reproductive career. Since working women in military environment are exposed to factors like mobility, shift duty, anaesthetic gases etc, it was decided to study their fecundity vis-a-vis housewives of same sodo economic status. In this study 204 subjects returned the questionnaire with a response rate of 68%. It was found that higher shades of subfecundity exist among women engaged in military service but does not reach the level of statistical significance (p=>0.05) to attribute it to the work environment. PMID- 27365660 TI - CORONARY RISK ANALYSIS - A STITCH IN TIME. AB - Coronary heart disease (CHD) is the major cause of sudden death amongst adults throughout the globe. Though the prevalence of CHD is increasing steadily all over, CHD amongst Indians is peculiar in the sense that it is more prevalent, more severe and appears at younger age. Development of CHD depends upon the status of various coronary risk factors in one's body. It has been observed that to measure the impact of risk factors for the cardiac health of a person, collective impact of all the known risk factors taken together should be calculated rather than individual risk factors. DEBEL (Defence Bio-Engineering and Electro-Medical Laboratory) is developing a cardiac risk analyser to calculate the absolute coronary risk of an individual in next 2,5 or 10 years and help in managing his coronary risk status. PMID- 27365661 TI - MANAGEMENT OF TYPE 2 DIABETES (NIDDM). PMID- 27365662 TI - OBESITY : A MODERN DAY PLAGUE. AB - Obesity is the presence of excess body fat. Unfortunately obesity is taken as a mere cosmetic problem and not a medical one. Today obesity is being 'dealt' with more by the self-proclaimed fitness experts running the rapidly mushrooming fitness centres rather than by medical professionals. But rather than merely a cosmetic problem, obesity should be viewed as a disease because there are multiple biologic hazards at surprisingly low levels of excess fat With the rapid pace of industrialisation and economic progress, today more and more jobs are becoming sedentary and dietary patterns are also changing with a decline in the cereal intake and increase in the intake of sugar and fats. However, inherited physiologic differences in response to eating and exercise are also important factors. Treating obesity can often be a frustrating experience for both the physician and the patient because of the great difficulty in maintaining weight loss over the long term. However, a clear understanding of the causes of obesity and a treatment strategy based on a combination of diet, nutrition, education, exercise, behaviour modification and social support can go a long way in containing this 'modern day plague' before it acquires epidemic proportions. PMID- 27365663 TI - HIV - 1 SUBTYPES, ITS IMPLICATIONS AND VIRAL DYNAMICS. AB - Subtyping of HIV has important implications for developing candidate vaccine and understanding the biological behaviour and dynamics of HIV transmission in various populations. The third variable region (V3) in the envelope gene of HIV-1 has been shown to be a major determinant influencing a number of biological characteristics of the virus. HIV-1 evolves by rapid mutation and by recombination, both processes actively contributing to its genetic diversity. Most of the multiple genetic subtypes and intersubtype recombination of HIV-1 that comprise the global pandemic have not been characterized by full genome sequencing. The development of an effective human immunodeficiency virus type-1 (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag and env genes. PMID- 27365664 TI - ORTHODONTIC ANCHORAGE ENHANCEMENT WITH LINGUAL ARCH. AB - In orthodontic treatment planning, involving the key question of preservation of the anchorage, lingual arch in association with the present day labial appliances provides a viable solution to the orthodontist The continuous wire lingual arch auxiliary, addresses the important aspect of anchorage conservation by enhancing the buildup of forces in the posterior region. It also facilitates the retraction of the anterior segments and the resultant correction of the soft tissues. PMID- 27365665 TI - FORGOTTEN FOREIGN BODIES IN BRONCHIAL TREE IN ADULT (A REPORT OF TWO CASES AND REVIEW OF LITERATURE). PMID- 27365666 TI - SOLITARY FIBROUS TUMOUR OF PLEURA. PMID- 27365667 TI - VIRAL ASSOCIATED HAEMOPHAGOCYTIC SYNDROME - A POST MORTEM DIAGNOSIS. PMID- 27365668 TI - ORGANOPHOSPHOROUS POISONING WITH INTERMEDIATE SYNDROME. PMID- 27365669 TI - MALIGNANT MIXED MULLERIAN TUMOURS. PMID- 27365670 TI - RIFAMPICIN INDUCED PLATELET DYSFUNCTION. PMID- 27365671 TI - KARTAGENER SYNDROME. PMID- 27365672 TI - AEROSOL ANTISEPSIS : AN EFFECTIVE AND USER FRIENDLY METHOD OF SKIN PREPARATION. PMID- 27365673 TI - RECURRENT ANTERIOR SHOULDER INSTABILITY. PMID- 27365675 TI - UNIVERSAL TONGUE BLADE FOR TONSILLECTOMY. PMID- 27365674 TI - ANTIHISTAMINES IN ALLERGIC RHINITIS - A COMPARATIVE ANALYSIS. PMID- 27365676 TI - UTILITY OF PARANASAL SINUS RADIOGRAPHY. PMID- 27365677 TI - NEWER CONCEPTS AND MANAGEMENT OF NEONATAL SEPSIS. AB - Despite extensive research into its patho-physiology, investigations and treatment, sepsis remains an important cause of neonatal morbidity and mortality. The incidence in developing countries is 10 times that in the developed world. A large number of pro-and anti-inflammatory cytokines (interleukins, eicosanoids, tumour necrosis factor-alpha, nitric oxide) have been identified, the interplay of which leads to the Systemic Inflammatory Response Syndrome (SIRS) which can have devastating consequences on all systems of the body. In India the common organisms include Staphylococcus, E coli, Klebsiella and Candida. A number of maternal and neonatal risk factors have been identified. The initial signs and symptoms are subtle and can easily be missed. Early investigations and screening tests are important and a promising number of new tests are being studied. The gold standard for diagnosis is a positive culture from a body fluid or local source in the presence of SIRS. The threshold for starting antibiotics should be low in high-risk neonates and broad spectrum antibiotics covering the likely organisms should be given intravenously in all suspected cases in a hospital setting. This should be continued for at least 24-48 hours (till negative reports are available) in suspected cases and for 2-3 weeks in proven cases. Prophylaxis is aimed at preventing nosocomial and cross infections. Strict hand-washing, meticulous asepsis protocols, identification of high risk groups and prompt and better screening tests are essential in controlling this problem. PMID- 27365678 TI - SEVOFLURANE - A NEW ERA IN INHALATION ANAESTHESIA. PMID- 27365679 TI - Manual Small Incision Cataract Surgery: Experience at a Military Hospital. AB - BACKGROUND: Small incision cataract surgery came into practice with the advent of phacoemulsification. However, manual small incision cataract surgery (SICS) is a useful alternative for those who do not have access to phacoemulsification machine. METHOD: A total of 69 cases of cataract were undertaken for manual incision cataract surgery and intra ocular lens (IOL) implantation using 6mm straight incision. The surgical technique and postoperative results are compared with the results of phacoemulsification and IOL implantation. RESULT: Average postoperative astigmatism was +/- 0.75 dioptres. Postoperative uncorrected visual acuity (UCVA) of 6/18 or better was observed in 51(71.9%) cases after first week of the surgery. CONCLUSION: The study concludes that both phacoemulsification and small incision cataract surgery with intraocular lens (IOL) implantation are effective methods. However SICS with IOL implantation is a useful alternative in the absence of phacoemulsification machine. PMID- 27365680 TI - Idiopathic Hypertrophie Pyloric Stenosis : Our Experience. AB - BACKGROUND: A typical infant with idiopathic hypertrophic pyloric stenosis is described as a male child, first in the order of birth with a positive family history. However our experience suggests otherwise which is presented in this report. Methods : A retrospective analysis of medical records of 8 infants, who were diagnosed to be suffering from idiopathic hypertrophic pyloric stenosis and subjected to surgical treatment, was undertaken. RESULTS: There were 5 (62.5%) males and 3 (37.5%) females. There was no family history and only one child (12.5%) was first born in the order of birth. One infant was preterm and one case (12.5%) had associated congenital anomaly (single kidney). Definitive diagnosis was established in 6 (75%) babies at admission whereas, other 2 cases (25%) required further evaluation. All the infants were in a state of moderate dehydration and in a varying state of hypochloremic alkalosis. The pH and serum chloride levels ranged from 7.52 to 7.67 and 86-94 mmol/L respectively. All were subjected to traditional Ramstedt's pyloromyotomy after having undergone vigorous correction of fluids and electrolytes for 24-48 hours. Intraoperatively, there was one iatrogenic mucosal perforation, which was closed with an omental patch. Postoperative feeding was initiated 12 hrs after surgery in 6 (75%) babies. CONCLUSION: Our series suggests a clinical profile of hypertrophic pyloric stenosis in our subset of patients which is different from what is described in literature. PMID- 27365681 TI - Psychological Correlates of Outcome after Coronary Artery Bypass Graft. AB - BACKGROUND: Psychological effects of Coronary Artery Bypass graft (CABG) have been of interest all over the world but there is a paucity of Indian work. METHODS: 30 patients undergoing CABG at a service hospital were included. All patients filled a specially designed proforma. Mini Mental Status Examination, Hospital anxiety and depression scale, Coronary scale, Seattle angina questionnaire and Euro-QOL 5D were performed before and seven days after CABG. RESULTS: 43.3% had significant anxiety and 30% had significant depression before CABG. Following CABG, 36.67% of the patients had significant anxiety while 40% had significant depression. On the Seattle angina questionnaire, physical limitation reduced from 71.6 +/- 7.9 to 53.1 +/- 14.6. There was significant improvement in treatment satisfaction from 37.8 +/- 6.1 to 59.4 +/- 4.2 following CABG. On th euro quality of life scale (EQ5D) health status improved from 38.17 +/- 9.51 before CABG to 68.5 +/- 5.28 after CABG. CONCLUSION: There is a significant incidence of anxiety and depression in patients undergoing CABG, both before and after surgery. PMID- 27365682 TI - Butorphanol-bupivacaine versus Fentanyl-bupivacaine for Extradural Analgesia during Labour. AB - BACKGROUND: Epidural injection of a combination of local anaesthetic drugs and opioids, is known to provide good analgesia for the first and second stages of labour, with minimal risk to the mother and the foetus. METHOD: 64 pregnant women were allocated to one of two groups in a double blind, randomised, prospective study design. The first group (n=32) received 15ml of 0.1% bupivacaine with 0.1 nignil (-1) butorphanol (1.5mg) and the second group (n=32) received 15ml of 0.1% bupivacaine with 2MUgml(-1) of fentanyl. RESULTS: The times of onset and offset of analgesia were comparable. More patients of the butorphanol group were sedated but arousable. The patient satisfaction levels were good in both groups and APGAR scores were comparable. CONCLUSION: Butorphanol and fentanyl when used in combination with 0.1% bupivacaine are effective, offer good patient satisfaction and are comparable in labour analgesia. Though more patients were sedated in the butorphanol group there was no maternal, foetal or neonatal adverse outcome and the drug appears to be a safe alternative to fentanyl in labour epidural analgesia. PMID- 27365683 TI - Comparative Analysis of Laser Assisted Endoscopie and Conventional Endoscopie Dacryocystorhinostomy. AB - BACKGROUND: Dacryocystorhinostomy (DCR) is the standard surgical treatment for epiphora caused by obstructions distal to the common canaliculus. Endoscopic DCR (EDCR) and laser assisted DCR (LAEDCR) are becoming increasingly popular alternatives. METHOD: 69 cases of EDCR were compared with 18 cases of LAEDCR. The success rates were noted at 01 week, 01, 03 and 06 months. The operating time required, incidence of adjuvant procedures, complications and post operative morbidity were recorded. RESULTS: At the end of 06 months, 100% and 95% success was achieved with LAEDCR and EDCR respectively. Operating time, complication rates and the incidence of adjuvant procedures required were lesser in the LAEDCR group. CONCLUSION: In our study both the procedures have comparable success rates, though LAEDCR has an edge over EDCR in terms of decreased duration of surgery, decreased post operative morbidity and lesser complications. PMID- 27365684 TI - Secondary and Delayed Bone Grafting in Alveolar and Anterior Palatal Clefts. AB - BACKGROUND: Surgical repair with suitable bone graft / substitutes plays an important role in rehabilitation of individuals with residual anterior palatal or alveolar defects associated with an oronasal fistula. METHODS: 52 cases were treated by secondary or delayed bone grafting of the alveolar defects in isolation or associated with defects of the anterior palate from July 2002 - Nov 2004. Dimension and the extent of the defects were assessed with the help of radiographs & maxillofacial CT. Cephalometric analysis, presurgical orthodontics and dentofacial orthopedics preceded surgical repair with cancellous graft from the iliac crest, followed by post surgical orthodontics and prosthetic rehabilitation. RESULT: Satisfactory results were achieved in 49 cases with three cases showing failure of graft acceptance. Postoperative clinical and radiological evaluation for all the patients was done at an interval of one, three and six months. Bone density and trabeculation was comparable to the adjacent bone within six months. CONCLUSION: Recreating the bony continuity of the maxillary arch followed by orthodontic correction of dental discrepancies achieves a comprehensive orthosurgical correction. PMID- 27365685 TI - A Comparative Study of Laparoscopic with Conventional Open Donor Nephrectomy in Renal Transplantation. AB - BACKGROUND: Laparoscopic donor nephrectomy (LDN) has been gaining popularity among kidney donors. There have been concerns about the safety and efficacy of the procedure as compared to open donor nephrectomy (ODN). We compare our results on LDN with ODN. METHODS: We retrospectively analysed our data of LDN and ODN. Duration of surgery, blood loss, period of hospitalisation, per oral intake and analgesic requirements. RESULT: 22 LDNs were done, the operation time ranged from 220-300 minutes, and blood loss from 100-150ml. In the first 10 laparoscopic operations four cases required conversion to open surgical dissection. Only one case was converted to open surgery in the subsequent 12 laparoscopic cases. Oral intake was started on the first postoperative day. Analgesic requirement in laparoscopy cases was less. Patients were mobilised on the first day after surgery. Patients were discharged by seventh day. There was no significant difference in the functioning of the graft after revascularisation in the recipient. CONCLUSION: Laparoscopic donor nephrectomy is a safe and effective technique of donor nephrectomy. PMID- 27365686 TI - Furlow's Palatoplasty for Cleft Palate Repair. AB - BACKGROUND: The major drawbacks of standard procedures of palatoplasty have been inadequate palatal lengthening, velopharyngeal incompetence, impaired maxillary growth with mid-face retrusion and high fistula rates. The Furlow's double opposing Z-plasty is accepted as one of the better procedures for treating cleft palates. METHODS: This paper compared Furlow's procedure to Veau Kilner Wardill's procedure performed on 63 patients from July 2000 till February 2005. RESULTS: The results were compared in terms of the fistula rates, palatal lengthening, nasal regurgitation, velopharyngeal incompetence, improvement in speech, hearing and maxillary growth. CONCLUSIONS: The Furlow's technique offered better results irrespective of the age, type and extent of the cleft in the palate. PMID- 27365687 TI - Endotracheal Tube Cuff Pressure Monitoring in Peripheral Hospitals. AB - BACKGROUND: An improvised monitor was designed in a peripheral hospital to measure the tracheal tube cuff pressures in patients intubated under anaesthesia. The aim of the study was to assess the efficacy of assessment of cuff pressure by the traditional palpatory method and to compare the improvised monitor with the standard monitor commercially available. The effect of nitrous oxide on the cuff pressure was also studied. METHODS: The tracheal tube cuff pressure of 80 patients undergoing general anaesthesia was assessed by palpation and measured with an improvised and standard monitor. RESULTS: The study showed that the tracheal cuff pressure recorded were higher than normal tracheal perfusion pressure in 40% of the cases with satisfactory palpatory assessment. The pressures recorded by the improvised monitor were comparable to that of the standard monitor. The use of nitrous oxide resulted in increase in cuff pressures over a period of time. CONCLUSION: An objective measurement by any equipment is superior to assessment of cuff pressure by palpation. The improvised monitor can be used to give a fair idea of the cuff pressures, in places where a standard monitor is not available. PMID- 27365689 TI - Multidetector CT Evaluation in Arterial Stenting. AB - BACKGROUND: Multidetector CT (MDCT) represents breakthrough in CT technology, significantly improving CT Angiography applications. METHODS: Twenty one patients with aortoiliac & branch aneurysms or stenosis were evaluated by Digital Subtraction Angiography (DSA) and Multidetector CT (MDCT) before and after endovascular repair. RESULTS: There were eight cases of aortic & branch aneurysms and 13 with stenosis. Four cases had aortic aneurysms, while one case had left subclavian artery aneurysm, thoracic aneurysm, femoral and popliteal artery pseudoaneurysms. Of the 13 cases with stenotic lesions, iliac stenosis was seen in eight patients. The others included carotid, vertebral, aortic, renal and aortic bifurcation stenotic. MDCT offered accurate information on shape and size of aneurysm, shape and patency of graft, the presence or absence of perigraft thrombosis or endoleaks, while in stenotic lesions it provided useful information on shape of graft, its location, its patency and the presence and quantity of distal flow. CONCLUSION: MDCT was found to be a potentially useful modality during initial evaluation and follow up of patient undergoing endovascular repair. PMID- 27365688 TI - Management of Vascular Injuries in a Forward Hospital. AB - BACKGROUND: Management of vascular injuries poses a challenging problem under warlike conditions. Several authorities recommend limb revascularisation only within first 6-8 hours, as the outcome after delayed revascularisation is poor. METHODS: A retrospective analysis of 61 consecutive patients with vascular injury in a forward hospital over a 25- month period was carried out. RESULTS: Vascular injuries constituted 3.1% of all injuries. The mean injury to treatment delay (lag time) was 11 hours, and 10 patients received treatment after 12 hours. The overall amputation rate was 15%, but only 6.5% for those revascularised within 12 hours and 44% for those undergoing surgery after 12 hours (Chi-square 4.59, p < 0.05). Presence of associated fractures was associated with an adverse outcome (Chi-square 4.24, p < 0.05), as was ligation in comparison to revascularisation (Chi-square 7.86, p < 0.005). Popliteal injuries were associated with a high amputation rate. CONCLUSIONS: Failure to revascularise (ligation of artery), presence of associated fracture, and restoration of circulation beyond 12 hours are associated with a high amputation rate. PMID- 27365690 TI - Nanotechnology - The New Frontier of Medicine. AB - Molecular nanotechnology is destined to become the core technology in 21(st) century medicine. Nanotechnology mean, controlling biologically relevant structures with molecular precision. Nanomedicine is exploring how to use carbon buckyballs, dendrimers and other cleverly engineered nanoparticles in novel drugs to combat viruses, bacteria, cancer and delivery of drugs. Medical nanorobots will be of the size of a microbe, capable of self-replication, containing onboard sensors, computers, manipulators, pumps, pressure tanks and power supplies. Building such sophisticated molecular machine systems will require molecular manufacturing to using massively parallel assembly lines in nanofactories. PMID- 27365691 TI - Second Trimester Uterine Rupture - An Unusual Case. PMID- 27365692 TI - Perfusion CT and Catheter Delivered Thrombolytics in Management of Acute Stroke. PMID- 27365693 TI - Meningococcal Vaccine: Which, When and for Whom? PMID- 27365694 TI - Outbreak of Meningococcal Infection amongst Soldiers Deployed in Operations. AB - BACKGROUND: Meningococcal infection may lead to life threatening meningitis and fulminant meningococcal sepsis. Sporadic cases of meningococcal infection have been reported in soldiers but no outbreak in soldiers has been reported earlier from India. This outbreak in soldiers serving in counter insurgency role under field setting was effectively controlled without compromising their operational commitment. METHODS: This is an epidemiological investigation and control of an outbreak of meningococcal infection, bringing out the predisposing factors and highlighting the role of early diagnosis and management of cases. Mass chemoprophylaxis in contacts was used as an effective control measure in the absence of vaccine in this institution based outbreak. RESULT: Out of a total of 17 cases reported, 14 presented as meningitis and three as meningococcemia. Two cases of meningococcemia ended fatally. Serogroup A of Neisseria meningitidis was responsible for this outbreak. Gross over- crowding was the predisposing factor. CONCLUSION: An outbreak of meningococcal infection in soldiers deployed in counter- insurgency role was effectively contained using mass chemoprophylaxis in the absence of meningococcal vaccine. PMID- 27365695 TI - Comparision of Nebulised Salbutamol and L-epinephrine in First Time Wheezy Children. AB - BACKGROUND: Salbutamol is the standard recommendation in bronchial asthma. However, the use of bronchodilators in wheeze associated respiratory infections including bronchiolitis continues to be controversial. The aim of this study was to compare the efficacy of nebulised salbutamol versus epinephrine in 'first time' wheezy children using clinical parameters and airway resistance. METHODS: Sixty children between two months to 60 months were recruited, 30 in each treatment group. Children received periodic (0, 20, 40 minutes) doses of either salbutamol (0.15mg/kg with 3ml saline subject to a minimum of 2.5mg) or laevo- epinephrine (1:1000, 0.5ml/kg subject to a max of 2.5ml with 3ml saline) via nebuliser along with oxygen. Changes in heart rate (HR), oxygen saturation (SpO2), respiratory rate (RR) and respiratory distress assessment instrument (RDAI) were assessed along with measurement of airway resistance using interrupter method (Hand held spirometer-Microloop with MicroRint module). RESULT: The respiratory status was better in the epinephrine group with significant improvement in RR, RDAI score, SpO2 and fall of airway resistance. There were no significant side effects noted in either group. CONCLUSION: Nebulised epinephrine is a useful and safe drug for wheezy children and is superior to salbutamol. This needs validation by large multicentric randomized blinded studies. PMID- 27365696 TI - Fractures in the Maxillofacial Region: A Four Year Retrospective Study. AB - INTRODUCTION: The incidence of maxillofacial injuries is on the rise due to motor vehicle accidents and increased incidence of violence in recent times. The aim of this retrospective study was to determine the incidence, aetiology, the pattern of fractures, their management with open reduction and internal fixation (ORIF) and complications, if any. METHODS: A retrospective analysis of 621 fractures in 361 patients managed by ORIF over a four year period was carried out. RESULT: The average age of patients was 24.3 years with a male to female ratio of 21.2:1. Panfacial fractures comprised 4.7%, frontal bone fractures 8.9%, orbital fractures 0.7%, naso-orbito-ethmoid complex (NOE) fractures 0.7%, zygomatic complex fractures 23.5%, fracture maxilla 11.5% and mandibular fractures 52.2% of all facial fractures. All the cases were successfully managed by ORIF under general anaesthesia (GA). Complications were noticed in 6.8% of cases in the form of reactive implants in 3.6%, deranged occlusion in 1% and infection at operated site in 1% cases which were managed satisfactorily. CONCLUSION: The findings of this study reveal sharp annual increase in the number of cases of maxillofacial trauma. Road traffic accidents (RTA) were the commonest cause and the age group most affected was between 20-25 years. ORIF of these fractures was chosen for its obvious advantages of direct anatomical reduction, early return to function and minimal complications. PMID- 27365697 TI - Profile of Live-born Infants of In-vitro Fertilisation. AB - INTRODUCTION: The Army Hospital (R&R) is the only service hospital providing in vitro fertilisation (IVF) facility. Neonatal characteristics of live-born infants at this centre over a two-year period are analyzed in this study. METHODS: Data on 504 consecutive live-born IVF infants over a two-year period (01 Feb 2007 to 31 Jan 2009) were analysed. RESULT: Of the 504 neonates, 190 (37.7%) were born by vaginal delivery, 156 (30.9%) by elective lower segment cesarean section (LSCS) and 127 (25.19%) following emergency LSCS. Maternal illness posing specific risk to the neonate was present in 165 out of 504 (32.7%). There were 239 (47.4%) preterm neonates. Males formed 51.8% of the cohort. Singletons accounted for 51.2%, while the rest (48.8%) were products of twin pregnancies. Small for gestational age neonates formed 22.6% (n = 114). A total of 20 (3.9%) infants had congenital malformations. There were 242 (48.1%) low birth weight neonates. A total of 128 (25.4%) neonates needed neonatal intensive care. Of the 504, there were 474 (94.1%) survivors while 30 (5.9%) did not survive. Twenty-nine (6.1%) neonates required readmission during the neonatal period. CONCLUSION: In our setting, neonates born following IVF appeared to be at increased risk of prematurity, multiple births and low birth weight. Proper obstetric and neonatal management can result in good neonatal outcomes. PMID- 27365698 TI - Verapamil as an Adjunct to Local Anaesthetic for Brachial Plexus Blocks. AB - BACKGROUND: Calcium channel blockers potentiate the effects of local anaesthetics. We examined the effect of adding verapamil to local anaesthetic solution on anaesthetic duration in patients undergoing surgery under brachial plexus block. METHODS: This study was a prospective, randomized, controlled, double blind study. Sixty patients undergoing elective upper limb surgery were divided into two groups of 30 each. Group A received 40 ml of 1% lignocaine with 0.25% bupivacaine, while Group B patients had 2.5 mg verapamil added. RESULT: Onset of sensory blockade time was marginally faster in Group B (23.2 +/- 3.94 minutes) as compared to Group A (23.9 +/- 4.13 minutes). However this difference was statistically not significant. The increase in duration of sensory blockade in Group B (185 +/- 46.52 minutes) as compared to Group A (157 +/- 44.28 minutes) was statistically significant (p= 0.011). Increase in duration of motor blockade in Group B (161 +/- 46.14 minutes) as compared to Group A (149 +/- 42,76 minutes) was statistically not significant (p = 0.15). Similarly prolongation of analgesic duration in Group B (318 +/- 69.54minutes) as compared to Group A (302 +/- 0.69 minutes) was statistically not significant (p=0.18). CONCLUSION: We conclude that adding verapamil to brachial plexus block can prolong sensory anaesthesia without any effect on analgesic duration. PMID- 27365699 TI - Early Cognitive Impairment: Role of Clock Drawing Test. AB - BACKGROUND: Folstein's Mini Mental Status Examination (MMSE) often fails to identify executive dysfunction even if quite severe. Detailed neuropsychological tests and extensive bedside tests are available to evaluate executive function, but most of them are time consuming. This study was done to determine the value of a Clock Drawing Test (CDT) as a simple tool to identify cognitive dysfunction in various neurological disorders and to assess its utility as an adjunct to MMSE in identifying executive dysfunction in a a busy out patient department (OPD). METHODS: A total of 81 patients suffering from neurological disorders and 81 controls were studied. All subjects received the MMSE and the CDT. The CDT is divided into an unprompted task that is sensitive to executive control (CDT 1) and a copying task which is not (CDT 2). RESULT: All the three tests (CDT 1, CDT 2 and MMSE) could recognize cognitive and executive function deficits, when compared with age and sex matched controls (p < 0. 001). CDT scores correlated strongly with the level of executive function deficits. CDT+MMSE detected 95% cases as abnormal as compared to 47% detected by MMSE alone. CONCLUSION: CDT along with MMSE can detect executive control deficits and cognitive deficits. The CDT 1 tests executive control performance, while CDT 2 tests posterior cortical deficits. PMID- 27365700 TI - Bullet and Blast ENT Injuries in Counter-Insurgency Area. AB - BACKGROUND: Many ENT injuries are not recognized easily, but they have the potential of increasing the morbidity. METHODS: ENT injuries managed in two tertiary care Level-IV hospitals between 2006 and 2007 were studied with a view to formulate strategy in efficient management of these cases. RESULT: Emergency bags did not carry readymade packs to control nasal bleeds. Routinely screening of ears in all blast injury cases in the 'Blast Injury Program' helped in early identification of hearing loss. Lack of sufficient stenting of nasal cavities resulted in severe nasal stenosis which was difficult to repair. Splinters lodged in pharyngeal wall escaped detection, resulting in concealed haemorrhage and shock. CONCLUSION: Nasal packs and epistaxis catheters must be included in emergency bags to minimize blood loss at first contact. Screening for ear trauma in all blast injuries increases detection rate and is beneficial to the soldier. Stenting of injured nasal cavities and early transfer to a tertiary care hospital could reduce morbidity. Plain radiography of head and neck areas could help detect splinters in vital areas and guide management. PMID- 27365701 TI - Pompe's Disease in Childhood: A Metabolic Myopathy. AB - BACKGROUND: Myopathy of metabolic origin in childhood occurs due to a variety of conditions. Pompe's Disease also known as Glycogen storage disease Type II, is a rare storage disorder with clinical presentation akin to spinal muscular atrophy. METHODS: A series of patients with suspected metabolic myopathy were reviewed at a tertiary care service hospital over a period of three years. The diagnosis was confirmed by estimation of acid alpha glucosidase activity. RESULT: At our centre, these cases presented with generalized hypotonia, organomegaly (hepatomegaly, cardiomegaly) and congestive cardiac failure. Infantile onset, the most severe form of Pompe's disease, was the commonest form accounting for 75% of the cases. Four of the babies with infantile onset Pompe's disease expired, three due to refractory heart failure and one to fulminant respiratory infection before 15 months of age. CONCLUSION: Pompe's Disease is now being increasingly diagnosed, due to definitive enzyme estimation facilities. With the recent availability of enzyme replacement therapy with Myozyme, the prognosis is likely to change for the better. PMID- 27365702 TI - Evaluation of Aerosol and Water Contamination and Control of Cross Infection in Dental Clinics. AB - BACKGROUND: The oral cavity is an unique environment which provides an ideal medium for bacterial growth. As a result of repeated exposure to the microorganisms present in blood and saliva, the dental health professionals and the patients are at a higher risk for developing many infectious diseases. A pilot study was carried out in the Dept of Dental Surgery, Armed Forces Medical College to assess the risk of cross infection in dental clinics. METHODS: Samples were collected from different dental surgeries of the Dept of Dental Surgery, Armed Forces Medical College and sent for microbiological culture and identification to the Dept of Microbiology, Armed Forces Medical College. The sampling was carried out in two stages, before and after implementing a set protocol. RESULT: All dental unit waterlines were coated with a well established biofilm made up of filamentous and bacillus-like microorganisms in first stage of study. There was marked reduction in the number of colonies from the samples collected during second stage. Same findings were observed in the samples of aerosol produced by ultrasonic scalers. CONCLUSION: The present study concluded that the new set protocol followed is significantly effective in reducing the microbial load in the water tubing, container and aerosol production. It is an effective measure for reducing the chances of cross infection in the dental surgery. PMID- 27365703 TI - Impact of Endoscopic Sinus Surgery on Symptom Manifestation of Chronic Rhinosinusitis. AB - BACKGROUND: Rhinosinusitis is a significant health problem which results in large financial burden on society. The study evaluated the prevalence and severity of individual symptoms of chronic rhinosinusitis (CRS) and the impact of endoscopic sinus surgery (ESS) on the symptoms and medication used in patients with CRS. METHODS: Patients with refractory CRS were assessed prospectively with ESS intervention. We studied the symptoms, change in medical therapy, complications of surgery and effect of other factors like smoking, polyposis and asthma on endoscopy and computed tomography scan scores. RESULT: A total of 81 patients underwent ESS for CRS. Post nasal drip (95%), headache (91%), nasal discharge (90%) and nasal obstruction (86%) were the commonest symptoms. Postoperatively, the highest improvement was seen in nasal blockage (87.2%), postnasal drip (84.4%) and headache (82.4%). Endoscopy scores were significantly worse in patients with polyps, asthma and smoking. A significant reduction in use of antibiotic and antihistaminics was seen post surgery. Seven patients who had extensive polyposis preoperatively, had recurrence and required revision surgery. Nasal synechiae formation and mild bleeding were the minor complications. CONCLUSION: Endoscopic sinus surgery results in significant improvement in the symptoms of patients with CRS alongwith a definitive decrease in antibiotic and antihistaminic requirement. We conclude that ESS is an effective treatment for CRS in those who fail to respond to medical treatment. PMID- 27365704 TI - Crown Cementing Strategy for Naval Divers. AB - BACKGROUND: A large number of personnel working in hyperbaric environment such as divers and submariners during escape drills report to the out patient department with split teeth, displacement of restoration and pain during ascent after diving. These symptoms are probably attributable to dental barotraumas. Therefore, a need was felt to undertake a study in this area, with a specific interest for treating these patients. METHODS: Sixty extracted single rooted premolar teeth were prepared and full cast crowns were cemented. Out of these, 20 were prepared with zinc phosphate, 20 with glassionomer and 20 with resin cement. After seven days of storage, each of the teeth in experimental group was pressure cycled 15 times to 3 atmospheres after which the force required to dislodge the crowns was tested on an Instron testing machine. RESULT: A significant difference was found (student's t test p value < 0.01) between the force required to dislodge the crowns with zinc phosphate cemented control group (141.70 +/- 38.62) and experimental group (16.92 +/- 10.13). Similarly a significant difference was observed in the glassionomer cemented control group (184.33 +/- 25.33) and experimental group (90.50 +/- 34.07). On the other hand, no difference was found between the resin cemented control group (289.15 +/- 81.48) and experimental (279.43+/-87.48) group. CONCLUSION: Within the limitations of this study and based on the results, it was concluded that environmental pressure cycling affected the retention of crowns cemented with zinc phosphate and glassionomer cement. Panavia resin cement used in this study appeared to be unaffected by environmental pressure cycling. On the basis of the results of this study, dental surgeons should consider cementing fixed prosthesis with resin cements for patients who are exposed to marked variations in environmental pressure, such as divers and submariners during escape drills. PMID- 27365705 TI - Sero-Epidemiological and Behavioural Survey of HIV, HBV and HCV amongst Indian Armed Forces Trainees. AB - BACKGROUND: Information on the emerging epidemics of Human immunodeficiency virus (HIV), Hepatitis B (HBV) and C (HCV) viruses in younger age groups in India is scanty due to paucity of representative, population based surveys and varied estimation methodology. This study was done to assess the point prevalence of HIV, HBV and HCV infections alongwith the epidemiological factors associated with these infections. Attitudes, beliefs and behaviour related to sexual and injecting drug practices, with a view to assess the need for introduction of screening program for the new entrants of the armed forces was also studied. METHODS: A multi-centric cross sectional serological and behavioural survey was carried out amongst newly enrolled trainees of the Armed Forces in 2004. The group was selected by multistage random sampling giving equal representation to all regions of India. Study subjects were interviewed using a pretested, validated questionnaire and screened for HIV, HBV and HCV infections by rapid tests. Standard confirmatory tests were carried out for trainees testing positive. Quality assurance measures were integral part of each activity. A database was created in MS Access and SPSS ver 11.0.1 was used for analysis. RESULT: Out of the 23,000 trainees included in the study, 22666 (98.55%) were included in the analysis. The age, formal education and age at first sexual intercourse of participants ranged from 16-25 years (median 20), 8-17 years (median 10) and 12-25 years, respectively. Partial knowledge about routes of spread of HIV was highly prevalent but complete knowledge was extremely low. Per thousand point prevalence of HIV, HBV and HCV was 0.61 (95% CI, 0.34-10.3, poisson), 9.31 (8.1-10.65) and 4.44 (3.61-5.39), respectively. Clustering of HIV (4.56 per 1000, 2.19-8.38) and HCV (30.54 per 1000, 23.67-38.78) and a higher number of HCV as compared to HBV was found amongst trainees from northeast. A statistically significant association was found between history of injecting drug use (other than medical) and HCV (p<0.05). CONCLUSION: Self-exclusion for recruitment as military trainees might have resulted in underestimation of general population figures but results provide region wise estimates unavailable till now. Concerted efforts are required in the current HIV/AIDS program activities to bring about knowledge and behaviour change amongst teenagers and young adults. PMID- 27365706 TI - Adult Stem Cell Plasticity: Dream or Reality? PMID- 27365707 TI - Surgical Management of Epilepsy: Emerging Paradigms. PMID- 27365708 TI - Aero-medical Considerations in Casualty Air Evacuation (CASAEVAC). PMID- 27365709 TI - Combined Periodontal and Orthodontic Treatment of Pathologic Migration of Anterior Teeth. PMID- 27365710 TI - Villar's Nodule: A Rare Presentation of External Endometriosis. PMID- 27365711 TI - Primary Cutaneous T-cell Lymphoma: Two Rare Presentations. PMID- 27365712 TI - Lead Toxicity due to Quack Remedies. PMID- 27365713 TI - A Case of Dysphonia. PMID- 27365714 TI - Jatropha Poisoning in Children. PMID- 27365715 TI - Spontaneous Pneumomediastinum Complicating Pneumonia in Children. PMID- 27365716 TI - Haemorrhagic Disease of Newborn presenting as Subdural Hematoma. PMID- 27365717 TI - Case of Toluene Abuse. PMID- 27365718 TI - Tramadol Dependence: A Case Report. PMID- 27365719 TI - Recurrent Bell's Palsy. PMID- 27365720 TI - A Case of Quinine Induced Blindness. PMID- 27365721 TI - Correlation between Systemic Lupus Erythematosus Disease Activity Index, C3, C4 and Anti-dsDNA Antibodies. AB - BACKGROUND: Therapeutic decisions in systemic lupus erythematosus (SLE) are based on the disease activity and nature of organ involvement. There are various clinical and laboratory methods to assess the lupus flares. METHODS: Fifty one SLE patients with active disease (lupus flare) were studied. Systemic lupus erythematosus disease activity index (SLEDAI), C3, C4 and anti-double stranded DNA levels were estimated and repeated monthly till remission. After remission these tests were done three monthly. Values of serological parameters were then correlated with SLEDAI score. RESULT: Thirteen (25.4%) patients had predominantly renal involvement while 38 (74.6%) patients had non-renal affliction. Musculoskeletal and mucocutaneous symptoms were the commonest features of lupus flare (90%). It was observed that 12 out of 13 (92.3%) patients with active renal involvement had low C3 levels and 11 (84.6%) had low C4 levels. The anti-dsDNA levels were elevated in all patients with predominant renal flare. In non-renal flare anti-dsDNA titre was raised only in 35% cases. Low C3 and C4 levels were noticed in 43% and 53% of non-renal flares respectively. Significant positive correlation was noticed between SLEDAI score and anti-dsDNA levels (0.01 level two-tailed prediction) and a significant negative correlation was observed with SLEDAI and C3, C4 levels (0.01 and 0.05 levels, two-tailed prediction) in our patients. On subgroup analysis it was noticed that this correlation is stronger for renal lupus. Negative correlation of SLEDAI and complement levels was not observed in non-renal flares. CONCLUSION: Calculation of SLEDAI is a vital clinical tool for assessment of SLE patients. Serial estimation of anti-dsDNA titre, C3 and C4 levels help us diagnose lupus flare and make appropriate therapeutic decisions in patients with high SLEDAI score. PMID- 27365722 TI - Laparoscopic Suture Rectopexy: An Effective Treatment for Complete Rectal Prolapse. AB - BACKGROUND: The study was undertaken to validate the efficacy of laparoscopic suture rectopexy as the treatment modality of choice for complete prolapse of rectum. METHODS: Data was prospectively collected and analyzed on 36 patients who underwent laparoscopic suture rectopexy for full thickness rectal prolapse between May 2006 to May 2008. There were 10 male and 26 female patients in this study with a mean age of 43.5 years. The pre and postoperative course of each patient was followed up with attention paid to ano-rectal manometery pressures, first bowel movement, hospital stay, duration of surgery, faecal incontinence, constipation, recurrence and morbidity. Mean follow up period was 12 months (range 1-24 months). RESULT: One patient had conversion from laparoscopic to open surgery. while another had recurrence of prolapse in the follow up period. Mean duration of surgery was 115 (range 100-150) minutes. Postoperatively, the mean time for the first bowel movement was 40 (range 24-64) hours. Mean hospital stay was five (range 4-7) days. There was no significant postoperative complication except for one port site infection and one pelvic collection. Of the 20 patients who had varying degree of incontinence preoperatively, 16 (80%) showed improvement after surgery. Constipation was present in 15 (41%) patients preoperatively. Nine of these 15 patients (60%) improved as regards constipation after surgery. CONCLUSION: Laparoscopic suture rectopexy is both safe and effective operation for the management of complete prolapse rectum. The procedure carries minimal morbidity and helps improve the problems of incontinence and constipation. PMID- 27365723 TI - Bad Obstetric History: A Prospective Study. AB - BACKGROUND: Death of an infant in utero or at birth has always been a devastating experience for the mother and of concern in clinical practice. Perinatal mortality remains a challenge in the care of pregnant women worldwide, particularly for those who had history of adverse outcome in previous pregnancies. To assess the risk factors and outcome of pregnancies in cases of bad obstetric history (BOH) and compare the results with control group, this study was undertaken. METHODS: A prospective study from 2003 to 2007 was carried out in 79 pregnancies having BOH (history of unexplained stillbirth/neonatal death, three or more consecutive abortions etc). Test group was analyzed in terms of age, gravida, parity, risk factors and outcome in terms of preterm delivery, stillbirth, mode of delivery, birth weight, pregnancy complications and fetal distress. These parameters were compared with a systematic, randomly selected sample from rest of the deliveries. Necessary advice and treatment was given in cases of hypothyroidism, hypertension, antiphospholipid antibody (APLA) syndrome, gestational diabetes and other risk factors. RESULT: There was significantly higher incidence of malpresentations, hypertension, APLA, cervical incompetence, preterm deliveries and caesarean section in test group (p< 0.05). In this study, only 47 (59.49%) women out of 79 in BOH group were identified to have possible factor responsible for pregnancy losses. In 32 (40.51%), no probable causes could be identified. Nine (11.39%) patients were identified with more than one risk factor. CONCLUSION: APLA, hypertension, malpresentation, cervical incompetence, preterm deliveries and caesarean section were found significantly more in BOH group. In a large percentage of pregnancies with BOH, the risk factors for adverse outcome were not identified but pregnancy outcome was generally good in subsequent pregnancies with optimal antenatal care and advice. PMID- 27365724 TI - Newer versus Conventional Methods in the Diagnosis of Malaria: A Comparison. AB - BACKGROUND: This study attempts to evaluate and compare the efficacy of polymerase chain reaction (PCR) and quantitative buffy coat (QBC) assay with conventional Giemsa stained peripheral blood smear (PBS) examination in the diagnosis of malaria. METHODS: The study was conducted on 50 cases of smear positive malaria (group 1), 50 cases of clinically suspected malaria (group 2) and 15 healthy controls. All were subjected to Giemsa stain slide examination both thick and thin smear, QBC assay and PCR. PBS examination by Giemsa stain was taken as gold standard. RESULT: In this study the overall sensitivity and positive predictive value (PPV) of QBC assay in group 1 was 100% and that of PCR was 60% and 100% respectively. In group 2 the sensitivity, specificity, PPV and NPV of QBC assay was 100% and that of PCR was 71%, 100%, 100% and 73% respectively as compared to the gold standard. All the 15 healthy controls were negative by all the three assays showing 100% specificity. CONCLUSION: QBC assay was an excellent alternative to the conventional method as it is rapid and less time consuming and can directly demonstrate the parasite. Utility of PCR lies in species-specific diagnosis of falciparum malaria especially when there is a high degree of clinical suspicion and the report is negative by the other two methods. PMID- 27365725 TI - Prevalence of Celiac Disease in Children with Unexplained Failure to Thrive. AB - BACKGROUND: Gluten sensitive enteropathy or celiac disease (CD) is a disorder of small bowel that occurs upon exposure to gluten. A total of 67 children of either sex in the age group of 1-12 years with unexplained failure to thrive were studied for the prevalence of CD. METHODS: This was a cross-sectional study. It included detailed history, clinical assessment, estimation of anti gliadin (AGA), tissue transglutaminase antibodies (tTGA) and duodenal biopsy. Treatment with gluten free diet and follow-up of diagnosed cases was done for one year. RESULT: Sixteen cases (23.88%) had villous atrophy and positive serology, essential criteria for the diagnosis of CD. Forty six (69%) children were between 4-12 years of age. Male to female ratio was 2.3:1. Main symptoms were irritability (63%), diarrhea (56%) and weight loss (56%). Thirty seven (56%) children had weight less than 3(rd) percentile. tTGA was 100% sensitive and 90.2% specific. Duodenal biopsy showed decreased villious-crypt ratio in 81.25% and intra epithelial lymphocytosis in 81% children (p<0.000001). All the confirmed cases were advised strict gluten free diet for one year. On follow-up at six months, all children showed improvement in their symptoms and weight gain. CONCLUSION: CD is an important cause of unexplained failure to thrive in children. PMID- 27365726 TI - Modalities of Empowerment and Strengthening of Ex-servicemen. AB - BACKGROUND: Older people including ex-servicemen (ESM) in India are left to fend for themselves due to nuclear family system. Most children are not staying with them due to reasons such as acquiring of education or employment at distant places. These factors, coupled with deteriorating health with advancing age, change in value system and attitude amongst children who give more importance to materialism, it was felt necessary to find modalities to empower and strengthen ESM by available methods of including progressive weight training, yoga and meditation. METHODS: An interventional "Before and After" study was planned for a period of three months for in-patient ESM of a military hospital for common lifestyle diseases namely stroke, diabetes, senile depression, acute myocardial infarction and hypertension. Data of anthropometry, laboratory investigations and Hamilton rating scale for depression (HRSD) were taken before the study. These cases were then subjected to interventions (progressive weight training and spiritual health enhancement by yoga with meditation for three months) followed by same measurements again. RESULT: Statistically significant differences were observed before and after study with respect to pulse, respiratory rate, blood pressure, blood glucose, total cholesterol, low density lipoproteins (LDL), very low density lipoproteins (VLDL) and Hamilton depression score (p<0.05). The sleep pattern, sense of well being and posture while sitting to standing and walking with degree of support (stick/other person's help) improved considerably after the interventions. CONCLUSION: ESM are recommended to be trained much before retirement on progressive weight training and yoga in regimental centre/station institute. Provision to be made in existing ex-servicemen contributory health scheme (ECHS) polyclinics for employment of part time trainers for weight training and yoga. The physical and spiritual strengthening results in better capability to deal with old age and its problems. PMID- 27365727 TI - God made Capsulorrhexis. PMID- 27365728 TI - Infantile Tremor Syndrome. PMID- 27365729 TI - Combat Casualty Care. PMID- 27365730 TI - Warfare Injuries: History, Triage, Transport and Field Hospital Setup in the Armed Forces. AB - The treatment of war wounds has been an ancient art, constantly refined and adapted to reflect improvements in warfare strategies, weapons technology, transportation and damage control surgical practices. Throughout history, more soldiers died from disease than combat wounds, and misconceptions regarding the best timing and mode of treatment for injuries often resulted in more harm than good. Since the 19th century, mortality from war wounds steadily decreased as surgeons developed systems for rapidly moving the wounded from the battlefield to frontline hospitals. This article reviews the trends in military trauma management including triage, evacuation and field hospital setup in the Armed Forces. PMID- 27365731 TI - Blast Injuries. AB - Blasts injuries are responsible for about two-thirds of the conventional combat injuries during any military operation and account for a sizeable number during terrorist activities. The pathophysiology, clinical presentation and urgency of management vary significantly in primary blast injuries. These can lead to a wide range of overt and covert injuries, making diagnosis and management difficult. The clinical picture varies from acute respiratory distress to deafness with absence of any external injuries. Such patients are best identified and dealt with by a team of health care professionals well acquainted with battle field injuries. PMID- 27365732 TI - Fluid Therapy in Trauma. AB - Advances in shock resuscitation have occurred as a result of various military conflicts. Primary objective of trauma care is to minimize or reverse shock, avoiding the lethal triad of hypothermia, acidosis, and coagulopathy. The concept of Damage Control Resuscitation has evolved along with "damage control surgery" which includes hypotensive and haemostatic resuscitation, where small aliquots of fluid are infused, with hypovolaemia and hypotension tolerated as a necessary evil until definitive haemorrhage control can be achieved. In the initial stages of trauma resuscitation the precise fluid, crystalloid or colloid, used is probably not important as long as an appropriate volume is given. Haemostatic resuscitation includes early use of fresh frozen plasma in a 1:1 ratio with packed red cells with emphasis on whole blood, frequent cryo precipitates and platelets and the use of recombinant Factor VII for control of bleeding. PMID- 27365733 TI - Crush Injuries and the Crush Syndrome. AB - Combat related injuries bring untold misery to the victims and their loved ones. While injuries to vital organs cause immediate death, delayed mortality after reaching a hospital may occur due to several reasons, rhabdomyolysis or the crush syndrome being the most important. Crush syndrome predominantly affects the kidneys leading to renal failure, but the clinical picture may include acute respiratory distress syndrome, dyselectrolytaemia, disseminated intravascular coagulation, hypovolemic shock, arrhythmias and psychological trauma. Rescue, resuscitation and rehabilitation are onerous tasks and so a coordinated strategy with well trained team of professionals through various chains of evacuation is advocated. This article addresses these issues drawing upon the experience of the writer in combat casualty care in active operations. PMID- 27365734 TI - Head Injuries. AB - A combination of multiple injury types are typically involved in combat-related head injuries. Innovations in firearms, has led to new types of brain injuries from which we are able to learn much about how the brain responds to trauma. Traumatic brain injury is physical injury to brain tissue that temporarily or permanently impairs brain function. Initial treatment consists of ensuring a reliable airway and maintaining adequate ventilation, oxygenation, and blood pressure. Neurosurgical damage control includes early intracranial pressure control; cerebral blood flow preservation; and prevention of secondary cerebral injury from hypoxia, hypotension, and hyperthemia. Evacuation to the nearest neurosurgeon, avoiding diagnostic delays, and initiating cerebral resuscitation allow for the best chance for ultimate functional recovery. PMID- 27365735 TI - Spinal Cord Injuries. AB - Spinal Cord injury (SCI) is one of the most devastating and demoralizing ailment for both the patient and the medical practitioner. However, with the better understanding of the pathophysiology, better imaging modalities and emphasis on immobilization and rehabilitation has provided a ray of hope to such patients. The initial care aims at immobilization and evacuation by the classical log roll method and focuses on life-saving procedures. Basic imaging should be augmented with an MRI in doubtful cases. Immobilization either external or internal should be followed by early efforts for rehabilitation. The use of steroids during the acute phase has become controversial. The focus of latest studies has shifted to neuroprotective and regenerative agents. PMID- 27365736 TI - Management of Warfare Chest Injuries. AB - About 15 % of war injuries involve the chest. Fortunately 85% of patients sustaining chest injuries that reach medical facility will require clinical observation or a simple procedure like tube thoracostomy. Only one in six patients has life-threatening injuries that necessitate urgent operative repair. Early deaths are caused by airway obstruction, major respiratory problems such as tension pneumothorax or massive hemothorax, and cardiac tamponade. These conditions are easily managed if recognized promptly. Diagnosis and management of various components of chest injury requires clear judgment and indepth knowledge of pathophysiological mechanisms involved. The therapeutic goal in the war scenario is to restore normal physiology and thereby to restore cardiac and pulmonary function and evacuate the patient after stabilization. PMID- 27365737 TI - Abdominal Trauma in Combat. AB - Evaluating and managing patients with abdominal trauma remains one of the most challenging, resource-intensive and satisfying aspects of combat care. It demands a thorough understanding of the pathophysiology of trauma and shock, excellent clinical acumen and the ability to think and operate rationally in a chaotic milieu. PMID- 27365738 TI - Warfare Vascular Injuries. AB - Vascular injuries as a part of combat injuries have been recorded since times immemorial. Responsible for death due to exsanguination, the management of vascular injuries was ligation or amputation till the landmark Vietnam experience. The present day management has evolved with advances in modern technology and may start at the battlefield with the application of a tourniquet with the definitive treatment continuing beyond the combat operation theatres. A basic understanding of both blunt and penetrating vascular injuries will help minimize mortality and morbidity. PMID- 27365740 TI - Damage Control Philosophy in Polytrauma. AB - Severe traumatic injury is a public health care problem; with injuries accounting for 12% of the global mortality. Continued improvement in the survival of severely injured trauma patients is a paramount goal. Bailout/damage control surgery following trauma has developed as a major advance in surgical practice in the last twenty years. The principles of damage control surgery defied the traditional surgical teaching of definitive operative intervention and were slow to be adopted. Currently, damage control surgery has been successfully utilized to manage traumatic thoracic, abdominal, extremity, and peripheral vascular injuries. In addition, damage control surgery has been extrapolated for use in general, vascular, cardiac, urologic, and orthopaedic surgery. Stone et al were the first to describe the "bailout" approach of staged surgical procedures for severely injured patients. This approach emerged after their observation that early death following trauma was associated with severe metabolic and physiologic derangements following severe exsanguinating injuries. Profound shock along with major blood loss initiates the cycle of hypothermia, acidosis, and coagulopathy. During the 1980s, hypothermia, acidosis, and coagulopathy were described as the "trauma triangle of death" which makes the prolonged and definitive operative management of trauma patients dangerous. The management technique, now described as "damage control" by Rotondo et al, involves a multiphase approach, in which reoperation occurs after correction of physiologic abnormalities. PMID- 27365739 TI - Extremity and Orthopaedic Injuries. AB - The extremities remain the most common sites of wounding in combat, and are often a combination of injures to soft tissues, bones, vessels and nerves. While these injuries are managed only after life threatening injuries are tackled first, precise evaluation and prompt management strategies to attain optimal outcome remain the goals of treatment. With advancements in tourniquet science, broader spectrum antibiotics, use of negative pressure wound therapy, easier options for fracture stabilization and continuously evolving reconstructive procedures have all increased the tools available to the surgeon to salvage severely damaged limbs. PMID- 27365741 TI - Reconstruction in Warfare Injuries. AB - Traumatic injuries, especially in the combat setting, stress the surgical team that may be sited in a remote forward area, battling against paucity of time, resources and infrastructure. The lone surgeon may be faced with the arduous challenge of saving life. There is seldom thought given to reconstruction in this high-pressure situation. If the patient survives, morbidity for want of reconstruction can be severe and quality of life can suffer significantly. Reconstruction after 3 to 5 days is fraught with complications and usually does compromise outcome in the post-operative phase. The reconstructive surgeon should be involved early in the management as he can provide coverage for large soft tissue defects after aggressive debridement with panache. If the patient is haemodynamically stable, he should be transferred urgently, preferrably by air, to a higher centre with multi-specialty care, especially being equipped with an orthopaedic and trauma reconstructive surgeon. It has been proved beyond doubt that the healing improves significantly and there is marked decrease in morbidity if coverage of wounds is provided early, before colonized wounds get infected. PMID- 27365742 TI - Training in Trauma Management. AB - Considerable improvements have occurred in the care of injured patients since the times of World War I and II. This has been brought about not only by technological advances but also due to improved training of doctors and nurses in providing trauma care. Important elements of combat trauma training are realism, human-specific injuries and treatments, volume of trauma exposure, and team building. In all modern armies training is imparted using human simulators and mannequins, human cadavers, occasionally live animals but more often using animal tissues. Worldwide trauma training courses are mandatory for both paramedics and medical officers. There is a need to set up an organised system of trauma training in India and we, in the Armed Forces have to capitalize on the wealth of combat and non-combat trauma experience, in setting up such courses. PMID- 27365743 TI - Beating Heart versus Conventional Coronary Bypass Surgery: Our Experience. AB - BACKGROUND: Off-pump Coronary Artery Bypass (OPCAB) has become the standard surgical treatment of Coronary Artery Disease in most centres in India. It is clear from the current evidence that, in certain patients, OPCAB offers advantages over conventional Coronary Artery Bypass Grafting (CABG). Experience of this procedure in the Armed Forces is highlighted. METHODS: Retrospective analysis of 200 nonrandomized consecutive patients taken up for OPCAB and 200 conventional CABG between Jan 2005 and Dec 2007 was done. The European system for cardiac operative risk evaluation (euroSCORE) was used in all patients. Perioperative morbidity and mortality was compared in the two groups. RESULT: OPCAB was possible in 192 (96 %) out of 200 patients taken up for this procedure. Eight patients required cardiopulmonary bypass (CPB) to complete the revascularization. Incidence of reoperation for bleeding was 2.5% in OPCAB and 6% in CABG In the CABG group 2% patients developed severe bleeding complications, 3% required ventilation for more than 24 hour, 1% required renal replacement therapy, 1% had acute respiratory distress syndrome and 3.5% had neuro psychiatric manifestations. Incidence of these complications in OPCAB patients was lower or NIL. Overall mortality in the OPCAB group was 1.5% and 2% in the CABG group. However only one patient out of 192 (0.5%) who underwent successful OPCAB died, while two patients out of eight who required conversion to CPB in this group died. Incidence of stroke, deep sternal infection and mortality was similar in both groups. CONCLUSION: OPCAB is safe, effective and can be offered to more than 90% patients as the primary strategy for surgical myocardial revascularization. It has lower overall morbidity than conventional CABG Its main limitations are hemodynamic instability and inability to find a deeply embedded target vessel. Both these factors affect the outcome adversely making conventional CABG a better option in these situations. PMID- 27365744 TI - Comparative Evaluation of Two Techniques in Achieving Balanced Occlusion in Complete Dentures. AB - BACKGROUND: This study was undertaken to evaluate new technique, which claims to reduce treatment time while retaining the quality of treatment. The aim of this study was to compare complete dentures made by two techniques: with the use of face bow and without the use of face bow. METHODS: Twenty edentulous subjects were selected and each one received two pairs of complete dentures. Dentures were made from duplicated casts and each one followed different techniques. One technique used face-bow. Teeth were set using individualized wax rims as guides. In other technique an articulator was used, which avoids face-bow and teeth were set by the cast-analysis method. The number of occlusal contacts in centric relation and excursive movements were registered, in addition to this the opinion of patients regarding denture bearing during oral functions were taken. RESULT: Both groups had dentures with balanced occlusion, but the technique that avoids face-bow presented better results in regard to time taken, esthetics, comfort and stability. Balanced occlusion was provided even without face-bow and could be an alternative to obtain adequate complete dentures with a better prognosis. CONCLUSION: For achieving better quality of denture in the form of esthetics, phonetics and function in short duration of time; a new technique was used to establish balanced occlusion in complete denture prostheses. PMID- 27365745 TI - A Study of Psychological Correlates after Amputation. AB - BACKGROUND: Amputation of a limb affects almost all aspects of an individual's life. Psychological aspects are important factors for adjustment with the disability. METHODS: The present study was carried out on 50 consecutive male patients admitted to the Artificial Limb Centre. Base line and post therapy psychological assessment was carried out on Hospital Anxiety and Depression Scale (HADS). Trauma Symptom Inventory (TSI) was administered along with Millon Index of personality styles (MIPS). Psychological intervention was given to them on a therapy module proposed by authors. Data was analyzed with the help of SPSS. RESULT: Findings revealed significant differences in scores on HADS, before and after therapy (p<0.05). On Trauma symptom Inventory defensive avoidance and depression were noted to be above cut off level of (>65). Predominant personality styles were self indulgence and internally focused in motivating styles (mean prevalence score <50) and thought guided in thinking styles, dominating and controlling in behaving styles. The analysis of prevalence score of above 50 and less than 50 indicated Confident/Asserting (9B), Submissive / Yielding (11A), having significant change after therapy on score of anxiety (P<0.05). The personality dimension of dutiful and conforming had shown significant influence after therapy (P<0.05) on score of depression. CONCLUSION: The findings indicated psychological assessment and intervention is to be included as a part of the management after amputation. PMID- 27365746 TI - Magnetic Resonance Imaging in Evaluation of Periventricular Leukomalacia. AB - BACKGROUND: Improvements in perinatal care have resulted in increased survival of infants born prematurely, however neurological damage due to ischaemic infarction of the periventricular white matter is a problem of enormous medical, social and economic importance. Such vascular insult leads to destruction of the periventricular white matter, termed periventricular leukomalacia (PVL). This abnormality is the leading cause of significant morbidity in the survivors of premature birth. Magnetic Resonance Imaging (MRI) is perhaps the only imaging modality, which can accurately detect and quantify periventricular leukomalacia. METHODS: Magnetic Resonance Imaging was carried out in 45 children in the age group of 4 weeks to 8 years, with history of premature birth and perinatal hypoxia. These children had neurological deficits ranging from cortical blindness, spastic diplegia, spastic quadriplegia to severe mental retardation. The procedure was carried out on a 1.5 Tesla (Siemens Magnetom Avanto) MR system using available protocols for imaging the paediatric brain. RESULT: The study revealed that MR imaging could accurately identify areas of ischaemic infarction of the periventricular white matter both in the early as well as in the late stages. The pattern of abnormalities detected on MRI of the brain in these patients can be considered specific for PVL in the clinical background of premature birth and perinatal hypoxia. CONCLUSION: MRI is the ideal imaging modality to detect, quantify and accurately map the areas of brain affected by this hypoxic-ischaemic process. It is presently the gold standard for evaluating the neuroparenchyma in those with perinatal hypoxia. Advanced MR techniques like Diffusion Weighted Imaging (DWI), Proton MR Spectroscopy and DTI have shown great promise in our understanding of the pathophysiology and anatomic considerations of this disease process. PMID- 27365747 TI - Visual Inspection using Acetic Acid for Cervical Cancer in Low Resource Settings. PMID- 27365748 TI - Hypercalcemia Related Pancreatitis. PMID- 27365749 TI - Pachydermoperiostosis. PMID- 27365750 TI - Beyond Beauty: Botulinum Toxin Use in Anal Fissure: Reply. PMID- 27365751 TI - Beyond Beauty: Botulinum Toxin Use in Anal Fissure. PMID- 27365752 TI - Professional Conferences, Unprofessional Conduct. PMID- 27365753 TI - Infection Control in Health Care Facilities. PMID- 27365754 TI - Prevalence of Early Stages of Chronic Kidney Disease in Healthy Army Personnel. AB - INTRODUCTION: Chronic kidney disease (CKD) is associated with significant morbidity and mortality. Screening and detection of early stages of CKD can help institute interventions that may delay the progression of the disease. One aim was to study the prevalence of early stages of CKD in the Army. METHODS: A cross sectional study of Army Personnel in an Army cantt in Central India was carried out. All participants filled a structured questionnaire and anthropometric data was collected. Investigative profile included routine urine exam, semi quantitative microalbuminuria (MAU), serum creatinine, lipid profile and fasting blood glucose. Glomerular Filteration rate (eGFR) was calculated using the Modification of Diet in Renal Diseases (MDRD) study equation. RESULT: A total of 1920 subjects were examined with 731 (38.07%) from Arms and 1189 (61.93%) from Services. 348 were excluded and of the remaining 1572 subjects, 141 (8.97 %) had MAU and 157 (9.99 %) had deranged Albumin Creatinine Ratio (ACR). Mean eGFR by MDRD equation was 102 +/- 25.84 ml/min/1.73m (2) . Early CKD was seen in 150 (9.54 %) with 84 (5.34 %) in stage I CKD, 55 (3.5%) in stage II and 11 (0.7%) in stage III. Multiple logistic regression showed BMI > 23, the presence of DM and HTN were independent risk factors for CKD. CONCLUSION: 9.54% of healthy army personnel were found to have early stages of CKD. Institution of screening programs can result in early detection of CKD. PMID- 27365755 TI - Correlation of CD4+ T cell Count with Total Lymphocyte Count, Haemoglobin and Erythrocyte Sedimentation Rate Levels in Human Immunodeficiency Virus Type-1 Disease. AB - BACKGROUND: Studies in human immunodeficiency virus (HIV) infected adults have demonstrated association of total lymphocyte count (TLC) <1200/mm (3) and subsequent disease progression or mortality. The association of other surrogate makers such as haemoglobin (Hb), and erythrocyte sedimentation rate (ESR) with CD4 count and disease progression has also been suggested. This study was carried out to determine the relationship of CD4-positive T lymphocyte counts with TLC, Hb and ESR in HIV-infected individuals. METHODS: The study population comprised of 215 antiretroviral treatment naive HIV-1 infected adults. The CD4 positive T cell counts, TLC, Hb and ESR of study participants were measured. Spearman's rank order correlation and Receiver Operating Characteristic were used for statistical analyses. RESULT: The sensitivity, specificity, positive and negative likelihood ratios for cut-off value of TLC <1200/mm (3) for predicting CD4 counts <200 cells/mm (3) and <350 cells/mm (3) were 9.4 %, 100 %, not measurable and 1.1, and 6.1 %, 98.8 %, 5.13 and 0.95, respectively. The association of Hb (<10,11,12 g/dl and <10,12,14 g/dl for CD4 counts <200 cells/mm (3) and <350 cells/mm (3) , respectively), and ESR (<10, 20 and 30 mm fall after 1 hour) with these two CD4 counts cut-off values were suboptimal. CONCLUSION: This study reveals the poor association of TLC, Hb, and ESR with CD4 counts in HIV infected adults, thus highlighting the need to review the utility of these surrogate markers, for predicting CD4 counts in people living with HIV/AIDS. PMID- 27365756 TI - Occupational Exposure to Blood and Body Fluids amongst Health Care Workers in a Teaching Hospital of the Armed Forces. AB - BACKGROUND: Health care workers (HCWs) are at risk of infection with blood-borne viruses in the course of their work. Over 90% of these infections are occurring in low-income countries and most are preventable. However, the situation in the Armed Forces hospitals has always been thought to be much better than the public health facilities in India. The focus of the study was on assessing the exposure frequency amongst HCWs in a teaching hospital in the Armed Forces. METHODS: A cross-sectional survey amongst HCWs involved in collecting blood samples and administering injections in all wards of the hospital was conducted. Selection of study participants was by simple random sampling. A pre-tested questionnaire was administered by unlinked, anonymous method. RESULT: Total sample studied was 70. The proportion of HCWs experiencing exposure to blood body fluid splash (BBF) and needlestick injury (NSI) during last one week was 47.1 % and 31.43 %, respectively. The incidence density of BBF exposure was 537.14 per 100 person years and that of NSI episodes was 228.57 per 100 person years. The reasons for not using personal protective equipment (PPE) ranged from busy schedule (37.14%), non use of PPE by co-workers (67.14%), emergencies (91.43%) risk that patients may get offended by PPE use by HCWs (27.14%) to discomfort while using PPE (24.29%). All components of PPE were available as per only 34.29 percent. CONCLUSION: The high level of occupational exposure to blood and body fluids and consequent risk of infection amongst a group of HCWs in the Armed Forces highlights the urgent need for interventions to enhance the occupational safety of workers. PMID- 27365757 TI - A Randomized Clinical Trial of Three Different Steroid Agents for Treatment of Low Backache through the Caudal Route. AB - BACKGROUND: Although epidural steroids are commonly used for conservative management of sciatica, controversies exist regarding optimal approach, type and dose of steroids, volume of injectate and frequency of administration. This randomized comparative blinded study was undertaken to compare the efficacy of caudal methylprednisolone acetate with triamcinolone acetonide and dexamethasone acetate, for pain relief for sciatica associated with lumbar-disk herniations. METHODS: A Total of 163 patients with radicular pain due to lumbar-disk herniations, between 27-70 years of age were randomly divided into four groups: three were given epidural steroid injection therapy (methylprednisolone acetate, triamcinolone acetonide and betamethasone acetate) with bupivacaine; one group received bupivacaine alone via caudal approach. Injections were repeated every three weeks till a total of 210 mg of methylprednisolone (and equivalent) or three injections. Pain relief, disability and activity levels were assessed at 3, 6, 9 and 12 weeks interval. RESULT: Pain relief was present in all four groups by three weeks with no difference between the groups (p=0.006; 0.005; 0.0045; 0.005 respectively to baseline). By the 6 and 12 week, the three steroid groups had significant pain relief (p<0.001). Among these, both methylprednisolone and triamcinolone groups showed greater improvement in the finger-to-floor distance (p=0.006). A smaller proportion of patients in this group had residual sensory deficits (p=0.03) as compared to dexamethasone but difference was statistically insignificant. Overall pain relief was significantly better at all follow-up evaluations in the steroid group than in the control group (p<0.001 at all evaluations). CONCLUSION: Short-term improvement in leg pain and sensory deficits was observed in patients with sciatica due to a herniated nucleus pulposus with both epidural bupivacaine and steroids. All long-acting steroids had no statistically significant difference between their efficacy in pain relief but methylprednisolone and triamcinolone were more effective by the second injection as compared to dexamethasone which required a third injection in a significant number of cases. Differences between methylprednisolone and triamcinolone were insignificant. Complications were negligible and temporary. PMID- 27365758 TI - Red Cell Alloantibodies in Multiple Transfused Thalassaemia Patients. AB - BACKGROUND: Thalassaemia major patients require lifelong transfusion support due to which they are prone for alloimmunization to foreign RBCs. Alloimmunization can be prevented by extended phenotype match blood transfusion. The study was conducted to know the extent of problem of alloimmunization and to find important red cell antibodies in thalassaemia patients. METHODS: A cross-sectional study was conducted. A total of 32 thalassaemia patients were enrolled. The specimen was subjected to red cell alloantibody and autoantibody by column gel agglutination technique. R 1 (w) R 1 , R 2 R 2 , rr (papaine and non papain) and 11 cell panel reagent cells were used in screening and identification of alloantibodies respectively. RESULT: Six (18.8 %) subjects were alloimmunized. All alloimmunized subjects were recipient of more than 20 units of transfusion. Total seven clinically significant alloantibodies were identified. Anti E and anti c were commonest antibodies in four (12.5%) patients. CONCLUSION: Red cell alloimmunization is an important risk in thalassaemia patient. 71.4% of alloantibodies were anti E and anti c type. Extended phenotype match blood transfusion for Rh-c and Rh-E antigens or level 2 antigen matching stringency needs to be explored in preventing alloimmunization in thalassaemia patients. PMID- 27365759 TI - Changes in BiSpecteral Index (BiS) Values During Cardiopulmonary Bypass (CPB). AB - BACKGROUND: BiSpecteral Index (BiS) monitoring is standard monitoring regimen in anaesthesia practice. It has also been used in cardiac surgery. It is especially important due to the high incidence of neurological injury or dysfunction that occurs following CPB. This is a retrospective study of 33 cases that were monitored with BiS during the course of coronary artery or valvular surgery, including the period of CPB. METHODS: Thirty three cases monitored with BiS were studied retrospectively. RESULT: From the recordings it was determined that the value of BiS which was ranging between 40 to 60 after induction, dropped below 25 at the onset of CPB. This change was statistically significant (p<0.05). CONCLUSION: This decrease in the BiS value is probably a result of hypo-perfusion and due to clear, oxygen - poor priming fluid reaching the brain. Other periods of hypotension also correlated with the low values of BiS. This cerebral hypoxia which would occur at this time could be the cause of the incidence of neurological dysfunction that is known to occur following CPB. PMID- 27365761 TI - Dimensional Accuracy of Castings Fabricated with Ring-less and Metal Ring Investment Systems for Implant Supported Fixed Dental Prosthesis: An In-vitro Comparative Study. AB - BACKGROUND: The ring-less investment system is in use for dental casting, although there was no adequate scientific data to support its use either for conventional fixed dental prosthesis or implant retained fixed dental prosthesis. METHODS: An in-vitro study was undertaken to compare the vertical marginal accuracy of single full coverage metal restorations, between ring-less and metal ring investment techniques, using two different investment materials, for implant supported fixed dental prosthesis. Three groups were made of ten samples each. Group I consisted of metal ring with PCT(r) FlexVest (phosphate bonded investment material). Group II consisted of metal ring with Bellasun(r) investment material. Group III and the final group consisted of ring-less investment system and Bellasun(r) investment material. The wax patterns were prepared on a metal die, cast and finished. The cast restorations (samples) were again seated on the metal die and the accuracy of fit was evaluated by measuring the gap between the finish line on the die and the margins of the sample at four specific sites using a profile projector (Helios-350H, Microtecnica, LTF, Italy) having accuracy of 1um. RESULT: Mean marginal accuracy for Group-III was found to be the least (58.87 +17.87 um) followed by Group-II (97.23 + 16.37 um), and Group-I (109 + 7.55 um). However, Group I showed the least variability among the readings (SD=7.55). CONCLUSION: Ring-less system of casting can be recommended for use in fabricating implant supported fixed dental restorations. PMID- 27365760 TI - A Study of the Newer Prognostic Markers in Diffuse Large B Cell Lymphomas. AB - INTRODUCTION: Diffuse large B cell lymphomas (DLBCL) encompass a pathogenetically heterogeneous group of aggressive tumours that are rapidly fatal if untreated. Gene expression profiling studies have identified distinct molecular subtypes of DLBCL, one with an expression profile similar to normal germinal centre B cells (GCB subtype) and a second mimicking activated peripheral blood B cells (ABC subtype) having different prognostic significance allowing risk stratification of lymphoma patients and development of specific therapeutic strategies. METHODS: Twenty cases of DLBCL were included in the study and categorized into germinal centre and non germinal centre subtypes using the following antibody panel. CD10, Bcl-6, MUM1 and CD138. The germinal centre and non germinal centre subtypes were defined as under Germinal centre (DLBCL) CD10 + and/or Bcl-6 +, MUM1 -, CD138 - and Non germinal centre (DLBCL) CD10, Bcl-6 +/-, MUM1 +/-, CD138 +/-. RESULT: In our study of twenty cases thirteen were germinal centre DLBCL while seven of the twenty cases were non germinal centre type of DLBCL. 75% of the nodal cases and 62.5% of extra nodal cases were germinal centre B cell type. Overall survival in the GCB and non GCB groups was 91% and 14% respectively and the difference was highly significant statistically. CONCLUSION: This study validates the existence of prognostic subgroups of DLBCL in the Indian population. PMID- 27365762 TI - Management of Hyperglycemia in Critical Illness: Review of Targets and Strategies. PMID- 27365763 TI - The Woes of Waiting Wives: Psychosocial Battle at Homefront. AB - Few studies on stress have been carried out in soldiers and other paramilitary forces deployed in operational situations because of the security concerns, practical difficulties of conducting combat psychiatric studies and various other reasons. Studies on their families, who safeguard the family interests, during the period of absence of soldiers, have been even fewer. Significant contributions of researchers in this field were reviewed and suitably interpreted. Analysis revealed various types of stress and the multiple coping methods being practiced. It also highlighted various preventive and remedial measures being undertaken by waiting wives and their children. There is a need to understand and address the psychosocial issues of these families. PMID- 27365764 TI - Performing Laparoscopic Cholecystectomy using Diagnostic Laparoscope : Our Adaptations. PMID- 27365765 TI - Nitazoxanide : A Broad Spectrum Antimicrobial. PMID- 27365766 TI - Familial Glucocorticoid Deficiency. PMID- 27365767 TI - Fetal Reduction in Patient with Internal Jugular Vein Thrombosis following Ovarian Hyper Stimulation Syndrome (OHSS). PMID- 27365768 TI - Epithelial-Myoepithelial Carcinoma Ex Pleomorphic Adenoma in Breast : An Exotic Rarity. PMID- 27365769 TI - Acute Myocardial Infarction in a Young Patient of Rheumatic Heart Disease. PMID- 27365770 TI - Carcinoma Buccal Mucosa with Metastasis to Left Adrenal. PMID- 27365771 TI - Cranioplasty in Children with Split Rib Graft. PMID- 27365772 TI - Iron Overload : A Cause of Primary Amenorrhea. PMID- 27365773 TI - Harlequin Baby. PMID- 27365774 TI - Full Blown Case of Lipoid Proteinosis. PMID- 27365775 TI - An Unusual Cause of Superior Mesenteric Artery Syndrome in a Young Boy. PMID- 27365776 TI - Pneumorrhachis Associated with Bronchial Asthma. PMID- 27365777 TI - A Case of Interferon Induced Hypothyroidism. PMID- 27365778 TI - Preterm infants: is prophylactic surfactant therapy and early vitamin A supplementation the way ahead? PMID- 27365779 TI - Newborn care in India: a crying need of the hour. PMID- 27365780 TI - E-Medicine: transforming healthcare with information and communication technology. PMID- 27365781 TI - Biomarkers of malignant ascites-a myth or reality. AB - BACKGROUND: Ascitic fluid aspirate cytology, although reasonably specific is not a good screening tool for malignant ascites due to poor sensitivity. Simple test(s) on ascitic fluid or serum which can help differentiate between benign and malignant causes of ascites will be a boon. Ascitic fluid lactate dehydrogenase, cholesterol, and ferritin are the candidate markers evaluated in this study. METHODS: Ascitic fluid cytology was done on 30 patients of malignant ascites. The modalities used for diagnosing malignant ascites were positive peritoneal biopsy or CT scan evidence of hepatic metastases. Ascitic fluid biochemistry was done in all these 30 patients as well as 30 cases of non-malignant ascites. The parameters analysed were cholesterol, lactate dehydrogenase, and ferritin. The biochemical parameters were estimated in serum as well. RESULTS: Cytology had a sensitivity of 40% for the diagnosis of malignant ascites. Ascitic fluid cholesterol, lactate dehydrogenase, and ferritin had sensitivities of 70%, 74%, and 100%, respectively. Serum cholesterol, lactate dehydrogenase, and ferritin had sensitivities of 57%, and 91%, respectively. CONCLUSION: Hence, these biochemical markers in ascitic fluid as well as serum can be good screening tools for the diagnosis of malignant ascites. PMID- 27365782 TI - Effect of 0.5 mm larger donor corneal size on intraocular pressure following penetrating keratoplasty. AB - BACKGROUND: Glaucoma can develop after penetrating keratoplasty resulting in irreversible loss of vision. The incidence of post-penetrating keratoplasty glaucoma varies from 31% in the early postoperative period to 29% after three months. Various factors are responsible for the rise of intraocular pressure (IOP). This study was carried out to evaluate the effect of 0.5 mm larger donor corneal size on IOP following penetrating keratoplasty. METHODS: Patients were divided into two groups: group I was phakic and group II consisted of aphakic and pseudophakic patients. The same surgical technique was used for obtaining and suturing the donor graft. The viscoelastics and the postoperative regime also remained the same in all cases. IOP was measured by the rebound tonometer. RESULTS: The incidence of postoperative raised IOP in the first seven days in the phakic group was found to range from 16 mmHg to 25 mmHg and IOP in the aphakic/pseudophakic group ranged from 16 mmHg to 42 mmHg. The IOP in the phakic group after three weeks of surgery was around 12.3 mmHg and that in the pseudophakic/aphakic group was 14.8 mmHg-16.2 mmHg. In aphakic patients, IOP was controlled in the first six months with eyedrops Timolol 0.5% and tablet acetazolamide which was given only for short periods. IOP settled to < 12 mmHg with timolol 0.5% after six months. In the pseudophakic patients, IOP became normal by six months. These were inclusive of patients who had undergone anterior reconstruction and/or vitrectomy. CONCLUSION: The study proves that keeping the donor corneal size 0.5 mm larger does not affect IOP and that aphakia itself is a factor responsible for rise of IOP due to anterior chamber angle compression. PMID- 27365783 TI - BK polyoma viral infection in renal allograft recipients. AB - BACKGROUND: BK polyoma viral nephropathy (BKVAN) has emerged as a significant cause of renal allograft loss. The literature on BK viral infection from India is scarce. The study was therefore undertaken to evaluate impact of BK polyoma viral (BKV) infection on renal allograft recipients in Indian scenario from a service renal transplantation centre. METHODS: Renal allograft recipients who underwent graft biopsy formed the part of this descriptive cross-sectional study group. The clinicopathological profile of the patients was analysed. The diagnostic modalities employed were histopathology, immunohistochemistry using antibody for Simian virus 40 large T antigen along with real time quantification of the BK viral DNA load in the urine and the serum. RESULTS: One hundred forty seven renal allograft recipients were evaluated. 73.47 percent (108/147) patients presented with graft dysfunction and rest were protocol biopsies. There were 53 cases of rejection related diagnosis, 8 cases of graft pyelonephritis, 64 cases showed normal histology and rest exhibited miscellaneous causes. Nineteen percent (28/147) cases were positive for BKV DNA (viruria 26/147, 17.6% and viraemia 8/147, 5.44%. 3.4 percent (5/147) exhibited histological and immunohistochemical evidence of BKVAN. Nuclear enlargement, smudging and intranuclear inclusions along with plasma cell rich interstitial nephritis were important features observed on histopathology. Concomitant acute rejection was seen in 4/5 cases of BKVAN. All cases of BKVAN exhibited viraemia (> 2500 copies/mL), though cut-off values could not be defined statistically due to small sample size. Positive statistical correlation was observed between use of anti-thymocyte globulin (induction therapy and/or treatment of steroid resistant rejection, Pearson *(2) value 6.9, P=0.008) and rejection episodes (Pearson *(2) value 9.8, P = 0.007) with BKV infection. CONCLUSION: BK polyoma nephropathy should be added to the list of differential diagnosis considered for a renal allograft dysfunction. Renal biopsy remains the gold standard for diagnosis supplemented by non-invasive molecular techniques for screening and monitoring of BKV infection. PMID- 27365784 TI - Role of prophylactic surfactant in preterm infants. AB - BACKGROUND: Respiratory distress syndrome (RDS) in preterm neonates is caused by a deficiency or dysfunction of pulmonary surfactant. The physiological function of surfactant includes the ability to lower surface tension, as well as the ability to rapidly adsorb and spread. A wide variety of surfactant products have been formulated and studied in clinical trials. The present study was designed to find out whether prophylactic administration of surfactant leads to a significant decrease in the risk of neonatal mortality and neonatal morbidity. METHODS: This was an experimental study in which a total of 125 preterm newborns less than 34 weeks gestation were studied. One hundred preterm newborns (controls) less than 34 weeks gestation were managed in the conventional manner as per the existing protocols in the neonatal intensive care unit. Twenty-five consecutively delivered preterm newborns less than 34 weeks gestation were administered surfactant. Data regarding clinical outcomes including mortality and morbidity profile was collected and analysed. RESULTS: The mean duration of ventilation in the ventilated babies in the control group and the surfactant group was 129.8 +/- 43 hours and 85.7 +/- 46 hours, respectively; the difference being statistically significant. In the surfactant group, four babies (16%) died and in the control group, 27 babies (27%) died. The difference was not statistically significant. The number of babies developing retinopathy of prematurity and needing laser treatment for retinopathy of prematurity was greater in the surfactant group. CONCLUSION: Prophylactic administration of surfactant in preterm newborns of gestational age < 34 weeks is associated with a significant decrease in mean duration of ventilation and an increase in the incidence of retinopathy of prematurity. PMID- 27365785 TI - Umbilical cord blood plasma vitamin A levels in low birth weight (LBW) babies. AB - BACKGROUND: Role of vitamin A in reducing the mortality in infants more than six months of age is well known. Supplementing newborn infants with vitamin A within 48 hours of birth reduces infant mortality by almost a quarter, with the greatest benefit to those of low birth weight (LBW). Studies that could highlight deficiency states in neonates, particularly LBW babies by objective measurement of vitamin A levels would help in formulating the recommendations to supplement these babies with vitamin A. METHODS: Cord blood plasma vitamin A levels of 154 LBW babies with birth weight in the range of 1505-2455 were analysed for plasma vitamin A (retinol) levels by HPLC method. Samples of 55 babies with normal birth weight were also analysed. LBW babies were divided into two subgroups of preterm LBW and LBW-term small for gestational age (SGA). RESULTS: Of the 154 babies with LBW, 92 were preterm LBW and 52 were LBW-term SGA. Mean cord blood plasma vitamin A levels were significantly lower in the preterm LBW group (n = 92) compared to levels observed in babies with normal birth weight (n = 55) and LBW-term SGA subgroups (n = 62). There was no significant difference in the mean vitamin A values between the normal birth weight babies and LBW-term SGA group. There was significant positive correlation of cord blood vitamin A levels with birth weight in the entire set of (n = 154) LBW babies (r=0.37, P < 0.0001). CONCLUSION: This study revealed significantly lower cord blood vitamin A levels in the preterm LBW babies. The level of vitamin A in LBW babies also correlated with their birth weight. There are enough evidence to support causative association between vitamin A deficiency state and neonatal morbidity. Simple interventions like vitamin A supplementation during a crucial stage of an infant's life may be beneficial in the long run. There is a need to establish norms for vitamin A levels and seriously examine the role of vitamin A supplementation for LBW babies during the immediate postnatal period. PMID- 27365786 TI - Port exteriorisation appendectomy-our experience. AB - BACKGROUND: Laparoscopic appendectomy is conventionally performed using 3 ports, with division of appendicular base and artery using staples/endoloops/clips. Paucity of surgical laparoscope and laparoscopic disposables necessitated adoption of laparoscopic technique obviating the need for the above. We document our experience with the port exteriorisation appendectomy performed predominantly using two ports. METHODS: Between July 2008 and April 2009, 65 appendectomies were performed at a zonal hospital, of which 26 were performed using the contemplated technique. Technical challenges, conversions, operative time, complications, postoperative recovery, and cosmesis were analysed. RESULTS: Twenty-six patients (13 males and 13 females), with a mean age of 22.88 +/- 11.94 years, underwent port exteriorisation appendectomy. The median operative time was 20 minutes. Two cases (7.7%) needed conversion to open appendectomy. Dense adhesions necessitated addition of a working instrument/port in two cases (7.7%). Postoperative pain was < 25 by verbal response score. Visceral component predominated on the operative day, which got confined to port sites subsequently. One patient (3.85%) developed surgical site infection. Friable, gangrenous, short fibrosed appendix on a fixed caecum and very thick abdominal wall were its limitations. Postoperative recovery and cosmesis were excellent. CONCLUSION: Port exteriorisation appendectomy proves simple, safe, economical, and efficacious, when conditions favour its performance. However, difficult appendices warrant conversion to three ports technique or to open procedure. PMID- 27365787 TI - A comparative evaluation of rate of space closure after extraction using E-chain and stretched modules in bimaxillary dentoalveolar protrusion cases. AB - BACKGROUND: Aim of this study was to compare the rate of space closure between E chain mechanics in one side of upper arch and by elastomeric module with ligature wire on the contralateral side in same patient. METHODS: Thirty bimaxillary dentoalveolar protrusion cases were taken up for comprehensive fixed orthodontic treatment after extraction of all first premolars to retract both upper and lower anterior teeth. After initial alignment and levelling, alginate impressions were made for upper and lower arches and models constructed. In the upper arch model a vernier caliper was used to measure the extraction space in both sides from middle point of distal surface of canine to the middle most point of mesial surface of second premolar. This is the amount of space present before the onset of retraction mechanics. During space closure procedure two different retracting components were applied in right and left sides of each case. On right side elastic chain (E-chain) applied in both upper and lower arches and on left side elastomeric module with steel ligature (0.010") stretched double its diameter fixed in both arches. Both the mechanisms produced approximately 250-300 g of force as measured by a tension gauge. After onset of retraction mechanism all patients were recalled after every six weeks for three visits. In all these three visits modules and E-chains were changed. In all three visits impression was made, models constructed, and the remaining available space was measured by a vernier caliper up to 0.1 mm level variations. RESULTS: Mean value for total space closure in case of E-chain was 2.777 mm whereas in case of module with ligature wire the value increased to 3.017 mm. Mean value for rate of space closure in case of E-chain was 0.2143 mm, whereas in case of module with ligature wire the value increased to 0.2343 mm with a standard deviation of 0.001104 and 0.001194, respectively. The standard deviation for total space closure was 0.1305 for E-chain and 0.1487 for module with ligature wire. CONCLUSION: Space closure by elastomeric module with ligature wire is better than the E-chain. PMID- 27365788 TI - An interesting case of lump abdomen-gossypiboma. PMID- 27365789 TI - Fahr's syndrome: a rare clinico-radiologic entity. PMID- 27365790 TI - Macrodystrophia lipomatosa. PMID- 27365791 TI - Epidermolysis bullosae. PMID- 27365792 TI - Ophthalmia nodosa with intraocular caterpillar setae. PMID- 27365793 TI - Gastroschisis-antenatal diagnosis. PMID- 27365794 TI - Stent implantation of patent ductus arteriosus in a newborn baby. PMID- 27365795 TI - Varied presentations of hypothyroidism in children. PMID- 27365796 TI - Mystery of the missing loop. PMID- 27365797 TI - Endometriosis with salpingitis simulating acute appendicitis. PMID- 27365798 TI - Non-immune hydrops foetalis due to foetal tachyarrhythmia-management with transplacental amiodarone. PMID- 27365799 TI - Bilateral first rib fractures with pseudoarthrosis in a weight lifter. PMID- 27365800 TI - Recent advances in the role of non-invasive ventilation in acute respiratory failure. AB - Non-invasive positive pressure ventilation (NIPPV) is the technique of delivering mechanical ventilation without endotracheal intubation or tracheostomy. This is increasingly being utilised in both acute and chronic conditions. Strong evidence supports the use of NIPPV for acute respiratory failure (ARF) to prevent endotracheal intubation (ETI) and to facilitate extubation in patients with acute exacerbations of chronic obstructive pulmonary disease, to avoid ETI in acute cardiogenic pulmonary oedema (ACPO), and in immunocompromised patients. Weaker evidence supports the use of NIPPV for patients with ARF due to asthma exacerbations, with postoperative ARF, pneumonia and acute lung injury/acute respiratory distress syndrome. NIPPV should be applied under close monitoring for signs of treatment failure and, in such cases, ETI should be promptly available. A trained team, at an appropriate location, with careful patient selection and optimal choice of devices can optimise the outcome of NIPPV. PMID- 27365801 TI - Flightless Aedes mosquitoes in dengue control. PMID- 27365802 TI - Supplemental oxygen therapy in bleomycin-induced pulmonary toxicity: REPLY. PMID- 27365803 TI - Supplemental oxygen therapy in bleomycin-induced pulmonary toxicity. PMID- 27365804 TI - Detection of TB antigen by rapid test kit. PMID- 27365805 TI - Why quality in healthcare. PMID- 27365806 TI - Stress in the Indian Armed Forces: how true and what to do? PMID- 27365807 TI - Approach to neonatal thrombocytopenia: immature platelet fraction has a major role. PMID- 27365808 TI - The idea of research! PMID- 27365809 TI - Efficacy of flexible fibreoptic ureteroscopy and Holmium laser in retrograde intrarenal surgery for calyceal calculi. PMID- 27365810 TI - Evaluation of service quality of hospital outpatient department services. AB - BACKGROUND: It has become essential for hospital managers to understand and measure consumer perspectives and service quality gaps, so that any perceived gap in delivery of service is identified and suitably addressed. A study was conducted at a peripheral service hospital to ascertain any service gap between consumer expectations and perceptions in respect of the hospital outpatient department (OPD) services. METHOD: A cross-sectional study was conducted using SERVQUAL as the survey instrument, the instrument being validated for use in the hospital environment. Consumer ratings across 22 items of the survey instrument were collected in paired expectation and perception scores and then service quality gaps were identified and statistically analysed. RESULTS: Service quality gaps were identified to exist across all the five dimensions of the survey instrument, with statistically significant gaps across the dimensions of 'tangibles' and 'responsiveness.' The quality gaps were further validated by a total unweighted SERVQUAL score of (-) 1.63. CONCLUSION: The study concludes that significant service quality gaps existed in the delivery of the hospital OPD services, which need to be addressed by focused improvement efforts by the hospital management. PMID- 27365811 TI - Evaluation of mannitol as an osmotherapeutic agent in traumatic brain injuries by measuring serum osmolality. AB - BACKGROUND: The effectiveness of mannitol as an osmotherapeutic agent has never been subjected to a controlled clinical trial against placebo. Excessive use of mannitol in brain trauma patients can result in hyperosmolar states, hypernatremia and renal failure. This prospective study was conducted to evaluate the institutional protocol of using mannitol and assess its effects on serum osmolality. METHOD: Thirty patients with brain injury were included in the study. All the patients were given 100 mL of 20% mannitol three times a day as bolus infusion over 20-30 minutes. Serum osmolality was measured at 12 hourly intervals using Fiske osmometer. Mannitol administration was stopped whenever serum osmolality reached >= 320 mOsmol/Kg H2O. The total dose and duration of mannitol used to reach target osmolality of >= 320 mOsmol/Kg H2O was recorded. RESULTS: On 33% of all occasions, the patients had a serum osmolality which was in excess of the desired values (i.e. >= 320 mOsmol/Kg H2O). This indicates that the standard protocol of administering 20% mannitol 100 mL three times a day for more than 48 hours is perhaps excessive. CONCLUSION: The mannitol therapy should be guided by 12 hourly measurement of serum osmolality. Mannitol should be used for 48 hours only if facilities for measuring serum osmolality are not available. PMID- 27365812 TI - Incidence of thrombocytopenia in the neonatal intensive care unit. AB - BACKGROUND: Thrombocytopenia is the commonest haematological abnormality encountered in the neonatal intensive care unit (NICU). The incidence in neonates varies greatly, depending upon the population studied. The aim of the present study was to study the incidence of thrombocytopenia in the neonates admitted to the NICU. METHOD: The study was carried out in 258 consecutive eligible neonates from August 2007 to August 2009. Neonates were placed in two risk groups for thrombocytopenia, viz. high risk and low risk, depending upon the presentation, maternal history and any antenatal/perinatal events. Platelet counts were done on the first, third and fifth day of admission and thereafter every 72 hours till counts were normal. Low counts were collaborated with a peripheral blood smear. RESULTS AND CONCLUSION: The overall incidence of thrombocytopenia in the study group was 70% (182/258). The incidence in the high-risk group was 93.7% cases (134/143) and in the low-risk group was 41.7% (48/115). This difference was statistically significant. Factors associated with thrombocytopenia were sepsis, extreme low birth weight, intra-uterine growth restriction, birth asphyxia and pre-eclampsia in mothers. The most common severe bleeding manifestation was pulmonary haemorrhage. The overall mortality in babies with thrombocytopenia was 33% despite > 90% of these cases having received platelet transfusion. Of these pulmonary haemorrhage was the main cause of death in five cases. It is concluded that thrombocytopenia is very common in the NICU and should be actively looked for so that it can be managed appropriately. PMID- 27365813 TI - Effect of water temperature and duration of immersion on the marginal accuracy of provisional crowns. AB - BACKGROUND: Fabrication of fixed restorations is time consuming. It is vital that the prepared teeth be protected by means of an interim restoration till the time definitive prostheses can be delivered. Marginal adaptation is one of the most important requirements for an interim restoration. METHOD: This study was done to investigate the effect of water temperature and duration of immersion on the marginal accuracy of provisional restoration fabricated in autopolymerizing resin. The experimental model simulating a clinical situation was made. The test material was autopolymerizing methyl methacrylate. Specimens were subjected to different water temperatures for 5 and 10 minutes', duration for continuing the polymerization. Marginal accuracy was determined by a travelling microscope under 100 * magnification. RESULTS: The measurements were tabulated and statistically analyzed using two way ANOVA technique. Results showed significant difference at all water temperatures. Marginal gaps were least when crowns were polymerized at 20 degrees C for 5 minutes. CONCLUSION: Study concluded that polymerizing the polymethyl methacrylate resin provisional crowns by direct technique in the water maintained at 20-30 degrees C temperature for 10 minutes resulted in better marginal fit and this method can be utilized in clinical conditions for better results. PMID- 27365814 TI - Embryo reduction: our experience. AB - BACKGROUND: The transvaginal ultrasound-guided embryo reduction technique is a feasible option for the prevention and management of the medical and obstetric risks associated with high-order multiple pregnancy resulting from assisted reproductive treatment. METHOD: Multifoetal pregnancy reduction was carried out in 51 in vitro fertilisation pregnancies (IVF) and one intrauterine quintuplet pregnancy resulting from intrauterine insemination (IUI) using transvaginal approach under ultrasonographic guidance. RESULTS: Of the 52 embryo reduction procedures, 48 (92%) were performed between the seventh and eighth weeks of gestation, three between eighth and ninth weeks and one in the 10th week of gestation. Forty-nine patients (94%) underwent reduction from triplets to twins, two from quadruplet to twins, and one from quintuplet to twin pregnancy. The average time required for the embryo reduction was 5.0 +/- 0.5 minutes per sac in early gestation (6th-9th weeks), increasing to 8.5 minutes per sac for later procedures, due to technical difficulties brought about by increased embryo size and mobility. All embryo reduction procedures were successfully performed in a single session. CONCLUSION: Transvaginal ultrasound guided embryo reduction technique performed between seventh and eighth-weeks of gestation is an effective and safe procedure for embryo reduction. PMID- 27365815 TI - A clinical evaluation of midface advancement using intraoral distractors in management of bone stock deficiencies. AB - BACKGROUND: Cleft lip and palate patients present large osseous defects of the alveolus and midface hypoplasia. Traditional orthognathic surgery has limitations of relapse and limited age group. Distraction osteogenesis (DO) as a modality for midface advancement is relatively new. Modular internal distractor (MID) offers the advantage of patient compliance and minimal discomfort. The purpose of this study was to evaluate the versatility of intraoral distractors in midface advancement. METHOD: Nineteen patients with midface bone stock deficiency were selected for maxillary advancement. At the first surgery under general anaesthesia, after the osteotomy (Le Fort I/II), MID system was used. After distraction, evaluation was done for ease of the procedure, stability, and complications. Lateral cephalograms were evaluated at three stages: T1, pre distraction; T2, post-distraction; and T3, one year post-distraction. RESULTS: Significant changes showed 13.3 mm mean midface advancement bone formation at the pterygomaxillary region. The results were stable even at one year follow-up. CONCLUSION: Maxillary position improved in relation to the cranial base. This study showed that the MID was versatile in midface advancement in stability and patient compliance with minimal complications. PMID- 27365816 TI - Hyperbaric oxygen therapy in free flap surgery: is it meaningful? AB - BACKGROUND: Hyperbaric oxygen therapy is a recognised modality of treatment with applications in plastic surgery. This modality of treatment works by providing higher oxygen delivery to tissues. The benefits of this modality of treatment in free flap surgery were studied. METHOD: A randomised prospective study was done. Ten patients undergoing free tissue transfer by microvascular technique were studied. These patients were randomised into two groups. In Group 1 the patients were subjected to hyperbaric oxygen therapy postoperatively for seven days. Group 2 served as the control group. Patients in this group were not subjected to hyperbaric oxygen therapy. Patients were evaluated up to 14 days postoperatively. The flaps were evaluated for any flap loss, presence of venous congestion in the flap, flap oedema, and completeness of healing at the flap site. RESULTS: No significant difference was found in terms of flap survival, time to resolution of venous congestion, resolution of oedema, and period of postoperative recovery. CONCLUSION: Routine use of hyperbaric oxygen therapy does not result in better survival of free flaps. PMID- 27365817 TI - A study of seroprevalence of hepatitis B and hepatitis C among troops in Armed Forces. PMID- 27365818 TI - Visceral leishmaniasis co-infection in people living with HIV/AIDS. PMID- 27365819 TI - Branchial fistula: an imaging perspective. PMID- 27365820 TI - Appendiculo-caecal intussusception. PMID- 27365821 TI - Foetus-in-foetu. PMID- 27365822 TI - Clitoral reduction by ventral approach. PMID- 27365823 TI - Giant serous papillary cystadenoma. PMID- 27365824 TI - Portal vein embolisation. PMID- 27365825 TI - Immunoproliferative small intestinal disease-a rare extranodal marginal zone lymphoma of mucosa associated lymphoid tissue in the Indian subcontinent. PMID- 27365826 TI - Mirizzi syndrome. PMID- 27365827 TI - Orbital emphysema after sneezing: a case report. PMID- 27365828 TI - Anaesthetic management of a patient with Lown Ganong Levine syndrome-a case report. PMID- 27365829 TI - Sotos syndrome. PMID- 27365830 TI - Pentalogy of Cantrell: case report. PMID- 27365831 TI - Microsurgical treatment of gingival recession by subepithelial connective tissue graft: a case report. PMID- 27365832 TI - Rehabilitation strategies for partially edentulous-prosthodontic principles and current trends. AB - The prosthetic considerations for treatment of partially edentulous patients involve evaluation of important aspects such as presence of certain functional or skeletal deficits, orientation of the occlusal plane, free-way space, size and location of edentulous areas, number, strategic location and quality of the likely abutment teeth, vertical dimension, and the type of occlusion. A comprehensive evaluation, multidisciplinary approach and a sequential treatment plan, worked out in harmony with the patient's perceptions are important factors to ensure a successful outcome. This article discusses the principles, current trends and importance of clinical decisions in designing a treatment strategy when confronted with complex situations of partial edentulism. PMID- 27365833 TI - Working hand in glove with the orthopaedic surgeon: the era of the aggressive trauma reconstructive surgeon. PMID- 27365834 TI - Child with ventricular septal defect, absent left upper limb pulses and dysmorphism. PMID- 27365835 TI - Ether day: an intriguing history. PMID- 27365836 TI - Biomedical waste disposal: the way forward. PMID- 27365837 TI - Does catheter choice during embryo transfer alter the pregnancy rate? AB - BACKGROUND: Although every step in the in vitro fertilisation (IVF) procedure is important, the impact of embryo transfer (ET) on pregnancy rate (PR) is significant. Of all the crucial aspects of ET the type of catheter used and the technique of transfer on the PR has drawn the maximum attention and controversy. We aimed to compare the outcome of two different ET catheters on the PR. METHOD: A prospective analysis comparing the classical Frydman (Laboratoire CCD, France) and the soft Cook (Cook Medical, Indiana, USA) ET catheters was performed. Primary end-point was clinical pregnancy rate (CPR); secondary end-points were rates of difficult transfer. A total of 1,446 ETs were performed in women undergoing IVF treatment, of which 723 cycles were randomised to the Cook catheter and 723 to the Frydman catheter. RESULTS: It was observed that, although the Cook catheter was related to a slightly higher PR, the overall comparison failed to indicate a significant difference in CPR. It was also seen that the ease of transfer did not significantly affect the PRs. CONCLUSION: Individual variables during ET may not contribute significantly to the success of an IVF programme; however, a holistic approach encompassing all the factors is quintessential to improve the PR. PMID- 27365838 TI - Early predictors of success of non-invasive positive pressure ventilation in hypercapnic respiratory failure. AB - BACKGROUND: Non-invasive positive pressure ventilation (NIPPV) has emerged as a significant advancement in the management of acute hypercapnic respiratory failure. METHOD: Patients with hypercapnic respiratory failure requiring ventilation therapy (respiratory rate [RR] of > 30 breaths per minutes, PaCO2 > 55 mmHg and arterial pH < 7.35) were included in the study. Baseline clinical parameters and arterial blood gas (ABG) were recorded before initiating NIPPV. Clinical parameters including heart rate (HR), RR, oxygen saturation and ABG were revaluated at 1, 4, and 24 hours after initiation of NIPPV. Change in these parameters and need for intubation was evaluated. RESULTS: Of the 100 patients, 76 (76%) showed improvement in clinical parameters and ABG. There was improvement in HR and RR, pH, and PCO2 within the first hour in the success group and these parameters continued to improve even after four and 24 hours of NIPPV treatment. Out of 24 (24%) patients who failed to respond, 13 (54%) needed endotracheal intubation within one hour. The failure group had higher baseline HR than the success group. CONCLUSION: Improvement in HR, RR, pH, and PCO2 one hour after putting the patient on NIPPV predicts success of non-invasive positive pressure ventilation in hypercapnic respiratory failure. PMID- 27365839 TI - Role of CD34, vascular endothelial growth factor, and p53 in neoangiogenesis as correlated with stage of disease in colorectal carcinoma. AB - BACKGROUND: Angiogenesis is critical for the growth of colorectal carcinoma (CRC). Vascular endothelial growth factor is the most important angiogenic growth factor. METHOD: Fifty cases of CRC operated at INHS Asvini were studied by using immunohistochemical labelling of the tumours by using CD34, p53, and vascular endothelial growth factor (VEGF). RESULTS: Out of the 50 cases, 31 (62%) were positive for p53; of which 80.7% showed high expression. Significant staining (> 20% tumour cells showing positivity) was seen in 33 patients (66%), while 34% were negative. Of the 33 positive cases, 57.58% showed high-grade VEGF positivity. CONCLUSION: Vascular endothelial growth factor correlated significantly with the stage and grade of disease. Intra tumours microvessel density as calculated from CD34 expression increased with the stage and grade of the CRC. PMID- 27365840 TI - To determine the frequency of subtelomeric abnormalities in children with idiopathic mental retardation. AB - BACKGROUND: Cross-sectional study was carried out to determine the frequency of subtelomeric abnormalities in children with idiopathic mental retardation (MR). METHOD: Multiplex ligation-dependant probe amplification technique was used to detect subtelomeric abnormalities. RESULTS: Out of 35 children, 21 (60%) were males. Family history of MR was present in 23%. Main clinical features included speech delay in all motor delay cases (83%) and non-specific dysmorphic features (77%). CONCLUSION: Associated clinical features were more in children with intelligence quotient (IQ) < 50 (P < 0.05). Subtelomeric deletion (4q35) was observed in one child. PMID- 27365841 TI - Incidence of thrombocytopenia following phototherapy in hyperbilirubinemic neonates. AB - BACKGROUND: Thrombocytopenia has not been conclusively reported as a complication of phototherapy in any of the standard paediatric textbooks. MATERIALS AND METHOD: A prospective study in consecutively enrolled cohort of apparently healthy neonates, who developed indirect hyperbilirubinaemia and required phototherapy. Neonates having a base line platelet count of more than 150,000/mm(3) were included. Neonates having features suggestive of haemolysis, direct hyperbilirubinaemia, sepsis, anti-platelet drugs given to baby or mother, haemangioma, and other congenital anomalies were excluded. Platelet counts were performed at admission, 24 hours, 48 hours, and before discontinuing phototherapy. RESULTS: Out of 100 neonates included in study 35 (35%) had thrombocytopenia and a majority of neonates had mild thrombocytopenia (74%). The thrombocytopenia was seen in 26 (74%) cases during the first 24 hours of phototherapy and usually was not associated with clinical bleed. CONCLUSION: This study establishes an association of phototherapy as a cause of thrombocytopenia in hyperbilirubinaemic neonates. Though the incidence of thrombocytopenia is substantial yet it is clinically insignificant. This study helps the practitioner to be aware of this association and avoid unnecessary investigations, as thrombocytopenia was transient. PMID- 27365842 TI - Ultrasonic pachymeter: a little different role. AB - BACKGROUND: Ultrasonic pachymeter, though primarily used in refractive surgery and in glaucoma evaluation, can evaluate and compare the change in corneal thickness following extracapsular cataract extraction (ECCE), small incision cataract surgery (SICS) and phacoemulsification. METHOD: Six hundred patients were included in study. Patients were divided into three groups. Group 1 (200 eyes), group 2 (200 eyes) and group 3 (200 eyes) underwent ECCE, SICS, and phacoemulsification, respectively. Corneal thickness was evaluated pre operatively and postoperatively on day 1, day 2, day 7, day 15, and day 30 by ultrasonic pachymetry. RESULTS: Mean pre-operative corneal thickness in central, superior, inferior, nasal, and temporal quadrants is 525.35 +/- 32.34 MUm, 592.23 +/- 35.39 MUm, 595.66 +/- 31.68 MUm, 589.29 +/- 38.07 MUm, and 581.19 +/- 42.31 MUm, respectively. Postoperatively, a highly significant (P<0.01) increase in central corneal thickness was observed up to day 15 in ECCE, day 7 in SICS whereas it was up to day 2 in phacoemulsification. In superior quadrant, it is up to day 15 in ECCE and SICS whereas it is up to day 7 in phacoemulsification. In inferior quadrant, it was up to day 2 in all three techniques. In temporal quadrant, it is up to day 7 in ECCE and up to day 2 in SICS and phacoemulsification. In nasal quadrant, a highly significant (P<0.01) increase in corneal thickness was observed up to day 7 in ECCE and SICS whereas it was up to day 2 in phacoemulsification. CONCLUSION: Normal central corneal thickness is 525.35 +/- 32.44 MUm. At midperiphery, inferior cornea has maximum corneal thickness followed by superior, temporal, and nasal cornea. Postoperatively, pre operative value of corneal thickness and visual rehabilitation is achieved earliest in phacoemulsifiaction followed by SICS and ECCE. PMID- 27365843 TI - Markers for differentiation of tubercular pleural effusion from non-tubercular effusion. AB - BACKGROUND: The limitations of the conventional methods for diagnosing tuberculosis (TB) have spurred multi-faceted research activities throughout the world. This study aims to explore the levels of adenosine deaminase (ADA) and interleukins in pleural effusion of tuberculous, malignant, and miscellaneous origin for differential diagnosis of tubercular and non-tubercular effusion. METHOD: Adenosine deaminase was estimated by kinetic method employing xanthine oxidase while interleukins were measured using commercially available ELISA kits in pleural fluids of tubercular and non-tubercular origin. RESULTS: Pleural fluids INF-gamma, sIL-2R, TNF-alpha and ADA were significantly higher in TB group (n = 48) as compared to the non-TB group (n = 33) (mean +/- SD: INF-gamma; 1,958.7 +/- 896.5 pg/mL vs 356.9 +/- 733.6 pg/mL, sIL-2R; 6,101 +/- 1,753.8 pg/mL vs 3,166 +/- 2,611.1 +/- pg/mL, TNF-alpha; 195.5 +/- 292.1 pg/mL vs 59.7 +/- 128.9 pg/mL, ADA; 123.6 +/- 81.8 IU/L vs 48 +/- 48.5 IU/L, P < 0.01). CONCLUSION: INF-(is more sensitive and specific than ADA for the diagnosis of TB and should be added to the armamentarium of the diagnostic workup of pleural fluids for timely and accurate diagnosis of TB and differentiation of tubercular pleural effusion from non-tubercular effusion. PMID- 27365844 TI - An evaluation of fracture resistance of interim fixed partial denture fabricated using polymethylmethacrylate and reinforced by different fibres for its optimal placement: an in vitro study. AB - BACKGROUND: Polymethylmethacrylate (PMMA) is the most common material used to fabricate interim fixed partial denture (FPD). Several attempts have been made to improve fracture strength of this material with various methods of reinforcement, but its effect on the fracture resistance of interim FPD was not evaluated. METHOD: The study was designed in two stages. In the first stage various methods of reinforcement (glass fibre, polyethylene, combination of glass and polyethylene, and stainless steel) for interim FPD of PMMA were used and its effect on the fracture resistance of interim FPD was evaluated by three point bending test using universal testing machine. In the second stage, fibres which showed the highest fracture resistance value was used to ascertain the most appropriate site of placement for reinforcing interim FPD. Comparisons were made with analysis of variance. RESULTS: Stainless steel and glass fibres showed significantly higher fracture resistance value than polyethylene alone or mixed with glass fibres (P < 0.001). Fibre placement in the occlusal third region of the pontic resulted in higher fracture resistance than the other locations (P < 0.05). CONCLUSION: There was a definite improvement in the fracture resistance after reinforcement with fibres and stainless steel. The occlusal third region of the pontic is the most appropriate site of placement for reinforcement in interim FPD. PMID- 27365845 TI - Persistent pulmonary hypertension of the newborn: a review. AB - Persistent pulmonary hypertension of the newborn (PPHN) is a serious medical emergency in the neonatal period which occurs because of failure of transition of the foetal circulation into the normal circulation. The condition is characterised by persistently elevated pulmonary vascular pressures and despite numerous modalities of treatment available, the condition carries with it a high rate of mortality and morbidity. Early awareness of predisposing conditions and early diagnosis leads to better outcomes in PPHN. PMID- 27365846 TI - CD4 counts: a strong indicator of retinal and ocular lesions in HIV disease. PMID- 27365847 TI - What is your diagnosis? PMID- 27365848 TI - Growth hormone treatment in a child with X-linked hypophosphataemic rickets. PMID- 27365849 TI - Primary obturator internus pyomyositis. PMID- 27365850 TI - Internal resorption: an unusual form of tooth resorption. PMID- 27365851 TI - Percutaneous removal of intracardiac and intravascular foreign bodies. PMID- 27365852 TI - Extragenital lichen sclerosus with aetiological link to Borrelia. PMID- 27365853 TI - Symptomatic intestinal lipomas: our experience. PMID- 27365854 TI - Endodontic treatment for mandibular molars using ProTaper. PMID- 27365855 TI - An elusive case of acute abdomen. PMID- 27365856 TI - Partial androgen insensitivity syndrome: a diagnostic and therapeutic dilemma. PMID- 27365857 TI - Critical care management of molar pregnancy in a peripheral set-up. PMID- 27365858 TI - Gilles de la Tourette syndrome. PMID- 27365860 TI - Epidural steroids for low backache: is this a valid trial? PMID- 27365859 TI - Recombinant activated factor VIIa in a case of pregnancy with acute hepatic failure and massive blood loss. PMID- 27365862 TI - Medicolegal aspects-gossypiboma. PMID- 27365861 TI - Epidural steroids for low backache: is this a valid trial?: Reply. PMID- 27365863 TI - Biomarkers of malignant ascites-a myth or reality: Reply. PMID- 27365864 TI - Biomarkers of malignant ascites-a myth or reality. PMID- 27365865 TI - Ophthalmia nodosa with intraocular caterpillar setae. PMID- 27365866 TI - Numerical Treatment of Stokes Solvent Flow and Solute-Solvent Interfacial Dynamics for Nonpolar Molecules. AB - We design and implement numerical methods for the incompressible Stokes solvent flow and solute-solvent interface motion for nonpolar molecules in aqueous solvent. The balance of viscous force, surface tension, and van der Waals type dispersive force leads to a traction boundary condition on the solute-solvent interface. To allow the change of solute volume, we design special numerical boundary conditions on the boundary of a computational domain through a consistency condition. We use a finite difference ghost fluid scheme to discretize the Stokes equation with such boundary conditions. The method is tested to have a second-order accuracy. We combine this ghost fluid method with the level-set method to simulate the motion of the solute-solvent interface that is governed by the solvent fluid velocity. Numerical examples show that our method can predict accurately the blow up time for a test example of curvature flow and reproduce the polymodal (e.g., dry and wet) states of hydration of some simple model molecular systems. PMID- 27365867 TI - Early experience with digital advance care planning and directives, a novel consumer-driven program. AB - Barriers to traditional advance care planning (ACP) and advance directive (AD) creation have limited the promise of ACP/AD for individuals and families, the healthcare team, and society. Our objectives were to determine the results of a digital ACP/AD through which consumers create, store, locate, and retrieve their ACP/AD at no charge and with minimal physician involvement, and the ACP/AD can be integrated into the electronic health record. The authors chose 900 users of MyDirectives, a digital ACP/AD tool, to achieve proportional representation of all 50 states by population size and then reviewed their responses. The 900 participants had an average age of 50.8 years (SD = 16.6); 84% of the men and 91% of the women were in self-reported good health when signing their ADs. Among the respondents, 94% wanted their physicians to consult a supportive and palliative care team if they were seriously ill; nearly 85% preferred cessation of life sustaining treatments during their final days; 76% preferred to spend their final days at home or in a hospice; and 70% would accept attempted cardiopulmonary resuscitation in limited circumstances. Most respondents wanted an autopsy under certain conditions, and 62% wished to donate their organs. In conclusion, analysis of early experience with this ACP/AD platform demonstrates that individuals of different ages and conditions can engage in an interrogatory process about values, develop ADs that are more nuanced than traditional paper based ADs in reflecting those values, and easily make changes to their ADs. Online ADs have the potential to remove barriers to ACP/AD and thus further improve patient-centered end-of-life care. PMID- 27365868 TI - Change in prescription habits after federal rescheduling of hydrocodone combination products. AB - Nationally, health care providers wrote 259 million prescriptions for narcotic analgesics in 2012, or roughly one bottle of narcotics per US adult (1). In an effort to combat this ever-growing problem, the Drug Enforcement Administration changed the schedule of hydrocodone combination products from schedule III to schedule II on October 6, 2014. Fourteen Baylor Scott & White pharmacies encompassing a 200-mile radius in Central Texas were queried for prescription information on hydrocodone/acetaminophen, morphine, codeine/acetaminophen, and tramadol before and after the rescheduling to evaluate trends in prescription drug usage. While the rescheduling of hydrocodone combination products resulted in a reduced number of prescriptions and the total quantity dispensed of both the hydrocodone/acetaminophen 5/325 mg (Norco 5/325) and 10/325 mg (Norco 10/325) formulations, this was offset by a dramatic increase in alternative narcotic analgesics such as tramadol, codeine/acetaminophen 30/300 mg (Tylenol #3), and codeine/acetaminophen 60/300 mg (Tylenol #4), which do not have schedule II requirements. Additionally, there was no significant reduction in total pain medication prescribed after converting all agents to morphine equivalents. PMID- 27365869 TI - The impact of preexisting illness and substance use on functional and neuropsychological outcomes following traumatic brain injury. AB - Traumatic brain injury (TBI) is a significant public health problem in the US. Specific preexisting medical illnesses delay recovery after TBI and increase mortality or risk of repeat TBI. This study examined the impact of preexisting illness and substance use on patient rehabilitation outcomes following TBI. The Functional Independence Measure total score and Disability Rating Scale score measured functional outcomes at discharge from inpatient rehabilitation, while the Trail Making Test A and B and Total Trials 1-5 of the California Verbal Learning Test-II measured neuropsychological outcomes in 128 TBI survivors with moderate or severe TBI. Results showed that the presence of a heart condition or diabetes/high blood sugar was associated with lower functional outcomes by discharge. A history of a heart condition, stroke, or respiratory condition prior to TBI was associated with reduced cognitive flexibility. Those with preexisting diabetes/high blood sugar demonstrated poorer visual attention, visuomotor processing speed, and ability to learn and recall verbal information. Those with pre-TBI cancer also had greater auditory-verbal memory deficits. The findings showed that specific preexisting medical conditions are independently associated with lower functional and cognitive outcomes for patients with TBI. By screening patients for preexisting medical conditions, multidisciplinary TBI rehabilitation teams can identify patients who require more aggressive treatments or greater length of stay. PMID- 27365870 TI - Is nursing preceptor behavior changed by attending a preceptor class? AB - Nursing preceptors initiate new staff to the professional environment. To be successful, preceptors must be willing and knowledgeable in their role, both clinically and as an instructor. This study evaluated the effects of a 4-hour preceptor class to change preceptor behavior. Twenty-seven class participants commented on the class and their goals, and 18 completed a follow-up survey 2 months later. Among those 18, 90% had achieved at least one of their goals. One barrier to achieving planned changes was having the opportunity to precept over the time period. Participants indicated that improved listening skills, application of content, and team building all supported their improvement as a preceptor. PMID- 27365871 TI - Electronic cigarettes in the media. AB - Electronic cigarettes (e-cigarettes) are an increasingly popular source of nicotine and an increasingly popular topic in the media. Concerns about potential hazards associated with e-cigarette use and advertising, especially to adolescents, have led to studies on e-cigarettes in both traditional media (TV, mail, print, and outdoor advertising) and social media (websites, social networking sites, blogs, and e-mails). This review presents a narrative description of available studies related to e-cigarettes in the media. These articles have focused on promotion in both traditional and social media across a broad range of topics and have concentrated on target audiences, smoking cessation, harm reduction, and advertising. E-cigarette advertising is the most frequent topic in the published articles. Identifying the target audience also is a common objective in articles. The representation of e-cigarettes as a "healthier alternative" to traditional cigarettes and their use as a "smoking cessation aid" are main themes presented through all types of media. PMID- 27365872 TI - Tricyclic antidepressant overdose treated with adjunctive lipid rescue and plasmapheresis. AB - Tricyclic antidepressant poisoning remains a major cause of morbidity and mortality, particularly in the setting of suicidal attempts. The current standard of care for treatment is the administration of sodium bicarbonate infusion. Adjunctive lipid emulsion therapy and plasmapheresis have received attention recently. We report an 18-year-old patient who was successfully managed with lipid emulsion and plasmapheresis as adjuncts to sodium bicarbonate treatment and review some of the recent literature. PMID- 27365873 TI - Hydrocodone snorting leading to hypersensitivity pneumonitis. AB - We present a case of hypersensitivity pneumonitis caused by intranasal abuse of the prescription narcotic hydrocodone. The patient's clinical course was complicated by acute respiratory failure. A chest radiograph showed diffuse bilateral opacities. The patient was treated with noninvasive ventilation, a high dose of intravenous steroids, and bronchodilators, resulting in improvement of symptoms and radiographic appearance. PMID- 27365874 TI - Streptococcus agalactiae pyomyositis in diabetes mellitus. AB - Pyomyositis is an acute infectious disorder affecting the skeletal muscle. Although seen more commonly in the tropics, cases are being reported in temperate countries, including the United States. We report a case of nontropical pyomyositis in a 58-year-old diabetic man who presented with a vague chest wall swelling. His initial clinical presentation and imaging findings suggested an intramuscular hematoma. He later developed fever with increased swelling, and pyomyositis was diagnosed after an aspiration of the swelling yielded Streptococcus agalactiae. Aspiration of the abscess and the use of appropriate antibiotics led to complete resolution of the disease. We discuss possible factors in diabetics that might predispose them to pyomyositis. PMID- 27365875 TI - Inferior vena cava filter removal after prolonged dwell time of 2310 days. AB - Inferior vena cava filters are commonly placed for a variety of indications, often when anticoagulation is contraindicated. Although technical success is high and complication rates low, there are complications that are important to be aware of. We present the case of a 29-year-old woman with a prolonged filter dwell time resulting in complications. PMID- 27365876 TI - Isolated left posterior insular infarction and convergent roles in verbal fluency, language, memory, and executive function. AB - The posterior insular cortex-a complex structure interconnecting various brain regions for different functions-is a rare location for ischemic stroke. We report a patient with isolated left posterior insular infarction who presented with multiple cognitive impairment, including impairment in semantic and phonemic verbal fluency. PMID- 27365877 TI - Multiple bee stings resulting in ST elevation myocardial infarction (the Kounis syndrome). AB - Kounis syndrome consists of angina pectoris or myocardial infarction that is triggered by the release of inflammatory mediators in the setting of an allergic reaction. We present the case of a 61-year-old man who presented to the emergency department with anaphylaxis after being stung by >100 bees. During resuscitation, he subsequently developed ST elevation myocardial infarction. PMID- 27365878 TI - Using extracorporeal membrane oxygenation support preoperatively and postoperatively as a successful bridge to recovery in a patient with a large infarct-induced ventricular septal defect. AB - Rupture of the ventricular septum during acute myocardial infarction usually occurs within the first week. The event is usually followed by low cardiac output, heart failure, and multiorgan failure. Despite the many advances in the nonoperative treatment of heart failure and cardiogenic shock, including the intra-aortic balloon pump and a multitude of new inotropic agents and vasodilators, these do not supplant the need for operative intervention in these critically ill patients. This article describes the successful use of extracorporeal membrane oxygenation support as a bridge to recovery postoperatively in a patient with a large infarct-produced ventricular septal defect. PMID- 27365879 TI - Headache and abdominal pain in a young woman. PMID- 27365880 TI - Diffuse large B-cell non-Hodgkin's lymphoma and osteosclerotic myeloma with features of POEMS syndrome. AB - Multiple myeloma is a clonal hematopoietic neoplasm characterized by the proliferation of malignant plasma cells and associated end-organ damage, most notably lytic lesions in the bones. Osteosclerotic myeloma is an unusual variant of the disease in which the skeletal involvement is characterized by sclerotic lesions instead of classical lytic lesions. The disease can be associated with paraneoplastic symptoms, which have been given the acronym POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes). In addition to clonal plasma cell dyscrasias, some cases of POEMS syndrome are associated with Castleman's disease, and in 11% to 30% of the cases both Castleman's disease and clonal plasma cell proliferation are present. POEMS syndrome has rarely been described in patients with non-Hodgkin's lymphoma. PMID- 27365881 TI - Unrecognized hemoglobin SE disease as microcytosis. AB - Hemoglobin SE disease was first described during the 1950s as a relatively benign microcytosis, but increasing prevalence has revealed a predisposition towards vasoocclusive sickling. Recognition of SE hemoglobinopathies' potential complications is crucial so medical measures can be utilized to avoid multiorgan injury. PMID- 27365882 TI - A case of erythropoietic protoporphyria. AB - A 53-year-old Texas rancher developed a blistering skin rash that was sensitive to exposure to sunlight. He was referred to hematology with a presumptive diagnosis of porphyria. His peripheral blood counts were within normal limits, and a bone marrow examination revealed erythroid dyspoiesis and ringed sideroblasts. Serum, plasma, and erythrocyte protoporphyrin levels were elevated, the findings of which are consistent with a diagnosis of erythropoietic protoporphyria. This paper discusses the diagnosis and etiology of the porphyrias. PMID- 27365883 TI - Lactate levels with glioblastoma multiforme. AB - A 37-year-old woman with known glioblastoma multiforme was admitted for treatment of new deep vein thrombosis. Anion gap and plasma lactate levels were found to be elevated. Magnetic resonance imaging of the brain showed a stable, advanced glioblastoma multiforme. All causes of lactic acidosis, including infections and medications, were ruled out. Aggressive tumors have been shown to produce lactate levels in minute quantities in their microenvironment, which helps them metastasize and evade immune response and even radiation. PMID- 27365884 TI - Operative management of dermatofibrosarcoma protuberans of the breast. AB - Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumor with a tendency towards local recurrence. A 26-year-old woman presented with a 3 * 2 cm raised, purple-hued lesion on her left breast. Excisional biopsy identified the lesion as a DFSP. She underwent two additional operations to achieve widely clear margins. Operative excision is the primary treatment of dermatofibrosarcoma protuberans of the breast. PMID- 27365885 TI - Mammary-type myofibroblastoma with the nephrotic syndrome. AB - We describe a 23-year-old white man who presented with anasarca and a new periumbilical mass. He had preserved kidney function and laboratory findings consistent with nephrotic syndrome, including 9.7 g/day albuminuria. Serum serologies were positive for anti-SSa and anti-SSb and low complements but were negative for antinuclear antibody. Pathologic findings of the abdominal mass showed a mammary-type myofibroblastoma. A kidney biopsy revealed a diffuse proliferative and membranous immune-mediated glomerulonephritis with 10% interstitial fibrosis. This is a novel case of mammary-type myofibroblastoma associated with nephrotic syndrome mimicking a proliferative lupus pattern. PMID- 27365886 TI - Radiologic and histologic presentation of male mammary myofibroblastoma. AB - Mammary myofibroblastoma is a rare mesenchymal neoplasm that typically presents in older men and women. Less commonly, these benign tumors may also occur in soft tissues located outside of the breast, in which case they are referred to as mammary-type myofibroblastomas. The histologic composition of this benign spindle cell tumor can be markedly varied. We present a case of a large mammary myofibroblastoma in a male patient and discuss the typical imaging and histologic makeup of these tumors. PMID- 27365887 TI - An atypical presentation of blue rubber bleb nevus syndrome. AB - A 69-year-old white man presented with several episodes of hematochezia. Colonoscopy demonstrated multiple colonic blebs localized mainly in the distal transverse colon. Esophagogastroduodenoscopy, capsule endoscopy, and computed tomography of the abdomen did not reveal any abnormalities. The patient required several blood transfusions and eventually required a subtotal colectomy with ileosigmoid anastomosis for definitive bleeding control. Pathology was remarkable for multifocal vascular ectasia, consistent with the diagnosis of blue rubber bleb nevus syndrome. PMID- 27365888 TI - Amphetamine-related ischemic colitis causing gastrointestinal bleeding. AB - A 43-year-old woman presented with acute lower intestinal bleeding requiring blood transfusion. Multiple initial investigations did not reveal the cause of the bleeding. Colonoscopy performed 2 days later showed features suggestive of ischemic colitis. On detailed history, the patient admitted to using amphetamines, and her urine drug screen was positive for them. She was managed conservatively and advised not to use amphetamines again. She did not have any recurrence on 2-year follow-up. PMID- 27365889 TI - Syphilitic proctitis. AB - Syphilitic proctitis is a rare disease that usually presents as proctitis, ulcer, and neoplasm but lacks pathognomonic clinical symptoms. It is thus difficult to diagnose and may be treated inappropriately. We report a 31-year-old man who had a hard, ulcerated mass that occupied the rectal and sigmoid colon wall and mimicked a tumor. Fortunately, a biopsy of the mass demonstrated Treponema pallidum organisms consistent with syphilitic proctitis. The patient was successfully treated with intravenous benzyl penicillin, resulting in improvement in his proctitis. PMID- 27365890 TI - Pulmonary embolism following celiac plexus block and neurolysis. AB - Treatment of acute pain in chronic disease requires the physician to choose from an arsenal of pain management techniques tailored to the individual patient. Celiac plexus block and neurolysis are commonly employed for the management of chronic abdominal pain, especially in debilitating conditions such as cancer or chronic pancreatitis. The procedure is safe, well tolerated, and produces few complications. We present a case of pulmonary embolism following a celiac plexus block and neurolysis procedure. Further study is required to determine if celiac plexus ablation, alone or in combination with other risk factors, may contribute to increased risk for pulmonary embolism in patients seeking treatment for chronic upper abdominal pain conditions. PMID- 27365891 TI - Alcohol neurolysis of digital nerves. AB - Alcohol neurolysis is a well-established treatment in chronic pain management, often used in cases of intractable cancer-related pain that is refractory to other management therapies. We describe a 76-year-old woman with chronic toe neuritis who failed multiple treatments, including oral and topical analgesics, nerve blocks, and radiofrequency ablations. Alcohol neurolysis was performed via digit block of the toe resulting in 100% pain relief. PMID- 27365892 TI - Complex regional pain syndrome. AB - Complex regional pain syndrome (CRPS) is a neurologic disorder that often results in debilitating chronic pain, but the diagnosis may elude providers as it is one of exclusion. A history of trauma may be elucidated. We report a case of CRPS and review the clinical findings, appropriate workup, and treatment options for the patient. The patient we describe went through an extensive workup before receiving the correct diagnosis. Delay in diagnosis leads to prolonged suffering for the patient and, at times, unnecessary invasive debridement procedures. Raising awareness of this entity may help physicians make the correct diagnosis early, as well as initiate a collaborative effort between neurology, anesthesiology, and dermatology to provide the patient the most favorable outcome. PMID- 27365893 TI - Bevacizumab-induced pityriasis rubra pilaris-like eruption. AB - Pityriasis rubra pilaris is a rare inflammatory disorder characterized by follicular papules on an erythematous base often exhibiting islands of unaffected skin, follicular plugging, and palmoplantar hyperkeratosis. While vitamin A deficiency and autoimmune reactions have been hypothesized as possible etiologies of this condition, pityriasis rubra pilaris-like eruptions secondary to medications are extremely rare. To our knowledge, only three other cases have been reported, and pityriasis rubra pilaris has never been reported in association with bevacizumab. We present a 70-year-old man who developed erythroderma both clinically and histologically consistent with pityriasis rubra pilaris 10 days after intravitreal injection of bevacizumab for age-related macular degeneration. As immune-modulating drugs grow in their application for a host of diseases, recognition of associated medication complications is important. PMID- 27365894 TI - William Osler and Seymour Thomas, "the boy artist of Texas". AB - Critics consider the 1908-1909 portrait of William Osler by S. Seymour Thomas the best of six oil-on-canvas portraits of Osler done from life, including those by the more acclaimed US artists John Singer Sargent and William Merritt Chase. Osler called it "the best pictorial diagnosis I have ever seen" and told Thomas "I am at your service." A reappraisal of Seymour Thomas explains why his portrait makes us feel much as the artist did in Osler's presence, which is the original English-language definition of "empathy." Thomas told his subject that "I feel that you can look clear through me and see the wall on the other side." The intensity of Osler's gaze affects us similarly. The portrait satisfied Osler, but his wife, Grace Revere Osler, never warmed to it, perhaps because it depicts so clearly a highly focused, agenda-driven man. Helen Thomas used the portrait to promote her husband's business, and, after a tortuous history, the portrait eventually returned to Oxford University, where it now hangs inconspicuously in the Radcliffe Science Library. PMID- 27365895 TI - Facts and ideas from anywhere. PMID- 27365896 TI - Effects of Anthocyanin and Flavanol Compounds on Lipid Metabolism and Adipose Tissue Associated Systemic Inflammation in Diet-Induced Obesity. AB - Background. Naturally occurring substances from the flavanol and anthocyanin family of polyphenols have been proposed to exert beneficial effects in the course of obesity. We hypothesized that their effects on attenuating obesity induced dyslipidemia as well as the associated inflammatory sequelae especially have health-promoting potential. Methods. Male C57BL/6J mice (n = 52) received a control low-fat diet (LFD; 10 kcal% fat) for 6 weeks followed by 24 weeks of either LFD (n = 13) or high-fat diet (HFD; 45 kcal% fat; n = 13) or HFD supplemented with 0.1% w/w of the flavanol compound epicatechin (HFD+E; n = 13) or an anthocyanin-rich bilberry extract (HFD+B; n = 13). Energy substrate utilization was determined by indirect calorimetry in a subset of mice following the dietary switch and at the end of the experiment. Blood samples were collected at baseline and at 3 days and 4, 12, and 20 weeks after dietary switch and analyzed for systemic lipids and proinflammatory cytokines. Adipose tissue (AT) histopathology and inflammatory gene expression as well as hepatic lipid content were analyzed after sacrifice. Results. The switch from a LFD to a HFD lowered the respiratory exchange ratio and increased plasma cholesterol and hepatic lipid content. These changes were not attenuated by HFD+E or HFD+B. Furthermore, the polyphenol compounds could not prevent HFD-induced systemic rise of TNF-alpha levels. Interestingly, a significant reduction in Tnf gene expression in HFD+B mice was observed in the AT. Furthermore, HFD+B, but not HFD+E, significantly prevented the early upregulation of circulating neutrophil chemoattractant mKC. However, no differences in AT histopathology were observed between the HFD types. Conclusion. Supplementation of HFD with an anthocyanin-rich bilberry extract but not with the flavanol epicatechin may exert beneficial effects on the systemic early inflammatory response associated with diet-induced obesity. These systemic effects were transient and not observed after prolongation of HFD-feeding (24 weeks). On the tissue level, long-term treatment with bilberry attenuated TNF alpha expression in adipose tissue. PMID- 27365898 TI - Increasing our understanding of dying of breast cancer: Comorbidities and care. AB - Background: Screening and treatment for breast cancer have improved. However, attention to palliative support and non-cancer co-morbidities has been limited. This study identified types of care for and co-morbidities of persons dying of breast cancer compared to persons dying from all cancers and from non-cancer causes. Methods: Linked administrative data from population-based registries were used to examine 121,458 deaths in Nova Scotia from 1995 to 2009. Results: Breast cancer decedents' mean age was similar to that of all cancer decedents (72.0 versus 72.1 years), but their age spread was greater (20-59 years: 23.1% versus 16.7%; 90+ years: 11.2% versus 6.5%). Among women dying of breast cancer, 15.6% were enrolled in the diabetes registry and 15.1% in the cardiovascular registry, indicating that they had these non-cancer conditions prior to their death. Compared to all cancer decedents, breast cancer decedents were twice as likely to have dementia as a cause of death, and were less likely to die in hospital but more likely to die in a nursing home. Breast cancer decedents had place of death rates more similar to non-cancer than cancer decedents. Conclusions: Rates of dementia and diabetes among the breast cancer decedents were particularly note worthy in this novel study given that these comorbidities have not received much attention in the breast cancer research literature. Further collaboration with non-cancer disease programs is advised. The extent of adequate comprehensive palliative support for the 20% of the breast cancer decedents who are nursing home residents requires investigation. PMID- 27365897 TI - Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Accelerates the Progression of Renal Fibrosis in Lupus Nephritis by Activating SMAD and p38 MAPK in TGF-beta1 Signaling Pathway. AB - This study aim was to explore the effects of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in lupus nephritis and its potential underlying mechanisms. MRL/lpr mice were used for in vivo experiments and human proximal tubular cells (HK2 cells) were used for in vitro experiments. Results showed that MRL/lpr mice treated with vehicle solution or LV-Control shRNA displayed significant proteinuria and severe renal histopathological changes. LV-TWEAK shRNA treatment reversed these changes and decreased renal expressions of TWEAK, TGF-beta1, p-p38 MAPK, p-Smad2, COL-1, and alpha-SMA proteins. In vitro, hTWEAK treatment upregulated the expressions of TGF-beta1, p-p38 MAPK, p-SMAD2, alpha SMA, and COL-1 proteins in HK2 cells and downregulated the expressions of E cadherin protein, which were reversed by cotreatment with anti-TWEAK mAb or SB431542 treatment. These findings suggest that TWEAK may contribute to chronic renal changes and renal fibrosis by activating TGF-beta1 signaling pathway, and phosphorylation of Smad2 and p38 MAPK proteins was also involved in this signaling pathway. PMID- 27365899 TI - Surgical diseases of the esophagus in children. PMID- 27365900 TI - Esophageal replacement in children: Challenges and long-term outcomes. AB - Replacement of a nonexistent or damaged esophagus continues to pose a significant challenge to pediatric surgeons. Various esophageal replacement grafts and techniques have not produced consistently good outcomes to emulate normal esophagus. Therefore, many techniques are still being practiced and recommended with no clear consensus. We present a concise literature review of the currently used techniques and with discussions on the advantages and anticipated morbidity. There are no randomized controlled pediatric studies to compare different types of esophageal replacements. Management and graft choice are based on geographical and personal predilections rather than on any discernible objective data. The biggest series with long-term outcome are reported for gastric transposition and colonic replacement. Comparison of different studies shows no significant difference in early (graft necrosis and anastomotic leaks) or late complications (strictures, poor feeding, gastro-esophageal reflux, tortuosity of the graft, and Barrett's esophagus). The biggest series seem to have lower complications than small series reflecting the decennials experience in their respective centers. Long-term follow-up is recommended following esophageal replacement for the development of late strictures, excessive tortuosity, and Barrett's changes within the graft. Once child overcomes initial morbidity and establishes oral feeding, long-term consequences and complications of pediatric esophageal replacement should be monitored and managed in adult life. PMID- 27365901 TI - Clinical profile and management options of children with congenital esophageal stenosis: A single center experience. AB - AIM: The aim of the study is to review 7 patients with congenital esophageal stenosis treated in our institution from a diagnostic and therapeutic point of view. MATERIALS AND METHODS: This is a retrospective cohort study of 7 patients treated in Christian Medical College, Vellore from 2008 to 2014. The data were analyzed with regards to age at onset of symptoms, investigative findings, age at definitive treatment, pathology, modalities of treatment, and outcomes. RESULTS: Symptoms started within the 1(st) year of life in all children with a median age of 4 months. The time of delay in diagnosis ranged from 8 months to 81 months with a mean period of 37 months. About 6 patients had a lower esophageal stenosis and 1 patient had a mid-esophageal stenosis. About 4 of the 7 children underwent endoscopic balloon dilatation from elsewhere, with 2 of the above 4 undergoing a myotomy for a wrongly diagnosed achalasia. The number of dilatations ranged from 2 to 7 with a mean of 4 dilatations. Resection of the stenotic segment with end to end anastomosis was employed in 6 of the 7 patients, and a transverse colon interpositioning was done in 1 patient. An antireflux procedure was performed in one patient. Histopathological examination of the resected specimen revealed tracheobronchial remnant in 3 patients, fibromuscular thickening in 3 patients, and membranous web in 1 patient. Postoperatively, 2 of the 7 patients had asymptomatic gastroesophageal reflux and 1 patient had postoperative stricture requiring one session of endoscopic balloon dilatation. The mean follow-up period was 42 months (range 18-72 months). At the time of the last follow-up, all 7 patients were able to eat solid food, and none of the children were found to have symptoms suggestive of obstruction or gastroesophageal reflux. There was a statistically significant increase in the weight for age after the operation. CONCLUSION: Congenital esophageal stenosis is rare and often confused with other causes of esophageal obstruction. Although endoscopic balloon dilatation offers an effective temporary relief, we feel that definitive surgery is curative. Long term results following definitive surgery have been good, especially with respect to symptoms and weight gain. PMID- 27365902 TI - Pediatric esophageal substitution by gastric pull-up and gastric tube. AB - AIM: The aim of this study was to report the results of pediatric esophageal substitution by gastric pull-up (GPU) and gastric tube (GT) from a tertiary care pediatric center. MATERIALS AND METHODS: Retrospective analysis of the surgical techniques, results, complications, and final outcome of all pediatric patients who underwent esophageal substitution in a single institution was performed. RESULTS: Twenty-four esophageal substitutions were performed over 15-year period. The indications were pure esophageal atresia (EA)-19, EA with distal trachea esophageal fistula-2, EA with proximal pouch fistula-1, and esophageal stricture in two patients. Mean age and weight at operation were 17 months and 9.5 kg, respectively. GPU was the most common procedure (19) followed by reverse GT (4) and gastric fundal tube (1). Posterior mediastinal and retrosternal routes were used in 17 and 7 cases, respectively. Major complications included three deaths in GPU cases resulting from postoperative tachyarrhythmias leading to cardiac arrest, cervical anastomotic leak-17, and anastomotic stricture in six cases. Perioperative tachyarrhythmias (10/19) and transient hypertension (2/19) were observed in GPU patients, and they were managed with beta blocker drugs. Postoperative ventilation in Intensive Care Unit was performed for all GPU, but none of the GT patients. Follow-up ranged from 6 months to 15 years that showed short-term feeding difficulties and no major growth-related problems. CONCLUSIONS: Perioperative tachyarrhythmias are common following GPU which mandates close intensive care monitoring with ventilation and judicious use of beta blocking drugs. Retrosternal GT with a staged neck anastomosis can be performed without postoperative ventilation. PMID- 27365904 TI - The use of ileocolic segment for esophageal replacement in children. AB - AIMS: To evaluate and describe the procedure and outcome of ileocolic replacement of esophagus. MATERIALS AND METHODS: We review 7 children with esophageal injuries, who underwent esophageal replacement using ileocolic segment in Christian Medical College, Vellore, India between 2006 and 2014. RESULTS: The ileocolic segment was used in 7 children with scarred or inadequate esophagus. There were 4 girls and 3 boys, who underwent esophageal replacement using isoperistaltic ileocolic segment in this period. Age at presentation varied from 1 month to 14 years with an average of 4.6 years. The indications for ileocolic replacements were corrosive strictures in 5, failed esophageal atresia repair in one and gastric volvulus related esophageal stricture in another. The average follow-up duration was 37 months. One child with corrosive stricture lost to follow-up and died 2 years later in another center. Other 6 children were free of dysphagia till the last follow-up. CONCLUSIONS: Although the ileocolic segment is not commonly used for esophageal substitution, it can be useful in special situations where the substitution needs to reach the high cervical esophagus and also where the stomach is scarred and not suitable for gastric pull-up. PMID- 27365906 TI - TREAT FOR EA-TEF. PMID- 27365905 TI - Thoracoscopic repair of esophageal atresia with tracheoesophageal fistula: Basics of technique and its nuances. AB - AIM: To review the technique of thoracoscopic repair of esophageal atresia with tracheoesophageal fistula (TREAT) and results reported in literature and with authors' experience. PATIENTS AND METHODS: The technique of TREAT was reviewed in detail with evaluation in patients treated at authors' institution. The patients were selected based on selection criteria and were followed postoperatively. The results available in literature were also reviewed. RESULTS: A total of 29 patients (8 females) were operated by TREAT. Mean age was 2.8 days (range 2-6 days). Mean weight was 2.6 kg (range 1.8-3.2 kg). There was a leak in four patients, and two patients had to be diverted. They are now awaiting definitive repair. Twenty-one patients have completed a mean follow-up of 1.5 years and are doing well except for two patients who had a stricture and underwent serial esophageal dilatations. The results from current literature are provided in tabulated form. CONCLUSIONS: TREAT is now a well-established procedure and currently is the preferred approach wherever feasible. The avoidance of thoracotomy is a major advantage to the newborn and is proven to benefit the recovery in the postoperative patient. The technique demonstrated, and the tweaks reported make the procedure easy and is helpful to beginners. The outcome is very much comparable to the open repair as proven by various series. Various parameters like leak rate, anastomotic stricture are the same. The outcome is comparable if you TREAT these babies well. PMID- 27365907 TI - Determinants of gap length in esophageal atresia with tracheoesophageal fistula and the impact of gap length on outcome. AB - AIM: This study was aimed at identifying factors which may affect the gap length in cases of esophageal atresia with tracheoesophageal fistula (EA-TEF) and whether gap length plays any role in determining the outcome. MATERIALS AND METHODS: All consecutive cases of EA-TEF were included and different patient parameters were recorded. Plain radiographs with a nasogastric tube in the upper esophagus were taken. Patients were grouped into T1-T2; T2-T3; T3-T4; and T4 depending on the thoracic vertebral level of the arrest of the tube. During surgery, the gap length between the pouches was measured using a Vernier caliper and the patients were grouped into A, B, and C (gap length >2.1 cm; >1-<=2 cm and <=1 cm). The operative gap groups were compared with the radiography groups and the other recorded parameters. RESULTS: Total numbers of cases were 69. Birth weight was found to be significantly lower in Group A (mean = 2.14 kg) as compared to Group B (mean = 2.38 kg) and Group C patients (mean = 2.49 kg) (P = 0.016). The radiographic groups compared favorably with the intraoperative gap length groups (P < 0.001). The need for postoperative ventilation (70.83% in Group A vs. 36.84% in Group C, P = 0.032) and mortality (62.5%, 26.9% and 15.8% in Group A, B, and C, respectively, P = 0.003) co-related significantly with the gap length. CONCLUSION: Birth weight had a direct reciprocal relationship with the gap length. Radiographic assessment correlated with intraoperative gap length. Higher gap length was associated with increased need for postoperative ventilation and poor outcome. PMID- 27365908 TI - An assessment of quality of life of operated cases of esophageal atresia in the community. AB - AIMS: To evaluate the outcome of the operated children of esophageal atresia (EA) focusing on their early and late morbidity and mortality and quality of life (QoL) of survivors. SETTINGS AND DESIGN: A cross-sectional follow-up with retrospective analysis of available medical and surgical records of children who underwent repair for EA. MATERIALS AND METHODS: The medical records of the children who underwent repair for EA during the period from 2000 to 2011 at the Christian Medical College Hospital, Vellore, were collected retrospectively. Patients with parents were invited to visit the hospital for follow-up and nutritional status, digestive and respiratory symptoms, status of associated anomalies and QoL assessment of children done. QoL assessment was done using the PedsQLTM 4.0 generic core scales questionnaire comprising 4 scale scores: physical, emotional, social functioning, and school functioning. Mean scores are calculated based on a 5-point response scale for each item and transformed to a 0 100 scale with a higher score representing better QoL. STATISTICAL ANALYSIS USED: Statistical Package for Social Sciences (SPSS) version 16 using Chi-square or Fisher's exact test. RESULTS: Of 79 patients operated during the said period, there were 10 deaths and a total of 69 (87%) children survived. Of the 66 patients available for follow-up, we interviewed 30 parents and children while for the remaining 36 children, out-patients charts were reviewed retrospectively. Mean follow-up duration was 3.56 years. The height and weight for age measurement showed 47% and 56% of children respectively as below the 5(th) percentile. Main problems faced by operated EA children were of the respiratory (26%) and gastroesophageal (36%) tracts. In spite of the mentioned problems faced, the overall QoL of this group appeared good. In 23 of 30 patients, who answered PedsQLTM, more than 70% had scores >85 out of 100 in QoL scoring. CONCLUSIONS: While survivals of the children born with EA have improved, these children still face nutritional, respiratory, and gastroesophageal problems during their early childhood. In spite of this, the overall QoL of this patient group appears good. PMID- 27365909 TI - Review of esophageal injuries and stenosis: Lessons learn and current concepts of management. AB - AIM: To review the patients with esophageal injuries and stenosis with respect to their etiology, clinical course, management, and the lessons learnt from these. MATERIALS AND METHODS: Retrospective descriptive observation review of children with esophageal injuries and stenosis admitted between January 2009 and April 2015. RESULTS: Eighteen children with esophageal injuries of varied etiology were managed and included, seven with corrosive injury, five with perforation due to various causes, three with mucosal erosion, two with trachea esophageal fistula (TEF), and one wall erosion. The five children who had perforation were due to poststricture dilatation in a child with esophageal atresia and secondary to foreign body impaction or its attempted retrieval in four. Alkaline button cell had caused TEF in two. Three congenital esophageal stenosis (CES) had presented with dysphagia and respiratory tract infection. Six corrosive stricture and two CES responded to dilatation alone and one each of them required surgery. Four of the children with esophageal perforation were detected early and required drainage procedure (1), diversion (1), and medical management (2). Pseudo diverticulum was managed expectantly. Among TEF, one had spontaneous closure and other one was lost to follow-up. All the remaining nineteen children have recovered well except one CES had mortality. CONCLUSION: Esophageal injuries though rare can be potentially devastating and life-threatening. PMID- 27365910 TI - A new approach for the management of esophageal atresia without tracheo esophageal fistula. AB - Long gap esophageal atresia (OA) is a challenging condition. While discussing the various methods of management available to us, we report the use of magnetic resonance imaging in a case of pure OA to judge the gap between two ends of the esophagus. PMID- 27365911 TI - Thoracoscopic excision of foregut duplication cyst: A case report and review of literature. AB - Thoracoscopy has major advantages over thoracotomy. We report a successful management of foregut duplication cyst thoracoscopically in a child with review of literature. PMID- 27365912 TI - Management of long segment congenital esophageal stenosis: A novel technique. AB - Congenital esophageal stenosis (CES) is a rare cause of dysphagia in children. Diagnosis is often apparent on esophagogram. Surgical treatment for the subtype with tracheobronchial remnants (TBR) includes resection and anastomosis of the stenosed segment, myectomy, enucleation of cartilage, etc., These procedures are not suitable if the stenosed segment is long. We present a case of a 5-year-old boy who was diagnosed as CES and was successfully managed with stricturoplasty with some innovative modifications. PMID- 27365913 TI - Unusual postoperative complication of minimally invasive transhiatal esophagectomy and esophageal substitution for absolute dysphagia in a child with corrosive esophageal stricture. AB - Esophageal substitution in children is a rare and challenging surgery. The minimally invasive approach for esophageal substitution is novel and reported from a few centers worldwide. While detailed report on the various complications of this approach has been discussed in adult literature, the pediatric experience is rather limited. We report the laparoscopic management of a rare complication which developed after laparoscopic esophagectomy and esophageal substitution. The timely recognition and management by the minimally invasive approach have been highlighted. PMID- 27365914 TI - Comparison Between Measured and Calculated Free Calcium Values at Different Serum Albumin Concentrations. AB - INTRODUCTION: Free ionic calcium is the metabolically active component of total calcium (TCa) in blood. However, most laboratories report TCa levels that are dependent on serum albumin concentration. Hence, several formulae have evolved to calculate free calcium levels from TCa after adjustment for albumin. However, free calcium can directly be measured using direction selective electrodes rather than spectrophotometric methods used in autoanalyzers. OBJECTIVES: This study compares the levels of free calcium obtained by measurement by direct ion selective electrode (ISE) and the one calculated as a function of TCa by formulae. MATERIALS AND METHODS: A total of 254 serum samples submitted to clinical biochemistry laboratory of a tertiary care hospital were analyzed for total protein, albumin, and TCa by standard spectrophotometric methods and for free calcium by direct ISE. Three commonly used formulae viz. Orrell, Berry et al. and Payne et al. were used to calculate adjusted TCa. Calculated free calcium was obtained by taking 50% of these values. RESULTS: A significant difference (P < 0.05) was observed between calculated free calcium by all the three formulae and measured free calcium estimated by direct ISE using paired t-test and Bland Altman plots. CONCLUSION: Formulae for predicting free calcium by estimating TCa and albumin lacks consistency in prediction and free calcium should be evaluated by direct measurement. PMID- 27365915 TI - Advanced Atherogenic Index for the Assessment of Consolidated Lipid Risk in Premature Coronary Artery Disease Patients in India. AB - INTRODUCTION: The high prevalence, severity, and prematurity of coronary artery disease (CAD) in the Indian population cannot be completely explained by the conventional lipid parameters and the existing lipid indices. AIMS AND OBJECTIVES: To calculate newly defined advanced atherogenic index (AAI) in premature CAD patients and compare it between cases and controls and Correlate its values with the existing indices. MATERIAL AND METHODS: One hundred and twenty premature CAD patients and an equal number of age and sex matched healthy individuals were included in this study. Lipid profile and nonconventional lipid parameters like oxidized Low density lipoprotein (OX LDL), small dense LDL (SD LDL), lipoprotein (a) apolipoprotein B (Apo B), and apolipoprotein A1 (Apo A1) were estimated and their values were used to define AAI and existing lipid indices like AI, lipid tetrad index (LTI) and lipid pentad index (LPI). RESULTS: The mean age of cases and controls was 37.29 + 4.50 and 36.13 + 3.53 years, respectively. The value of AAI was highly significant in cases (3461.22 +/- 45.20) as compared to controls (305.84 +/- 21.80). AAI has shown better statistical significance and correlation (P < 0.0001, r = 0.737) as compared to the earlier indices such as AI (P < 0.01, r = 0.52), LTI (P < 0.001, r = 0.677) and LPI (P < 0.001, r = 0.622) in premature CAD. Kolmogorov D statistic and cumulative distribution function plot has shown that AAI can discriminate cases and controls more accurately as compared to the earlier indices. CONCLUSION: Statistically AAI appears to be a better marker of consolidated lipid risk in premature CAD patients as compared to the earlier indices. PMID- 27365916 TI - Chikungunya Fever Among Patients with Acute Febrile Illness Attending a Tertiary Care Hospital in Mumbai. AB - BACKGROUND: Chikungunya fever (CHIK) is an arboviral disease. Dengue fever (DENG) and CHIK are indistinguishable clinically and need to be differentiated by laboratory investigations. PURPOSE: This study aimed at estimating the seroprevalence of CHIK mono-infection and CHIK and DENG dual infection in suspected patients. We also analyzed the age, sex distribution, joint involvement, and relation of joint movement restriction with visual analog scale (VAS). MATERIALS AND METHODS: Two hundred patients clinically suspected with DENG and CHIK were enrolled from a Tertiary Care Hospital in Mumbai from April 2012 to October 2013. The detailed history and examination findings were recorded. Serum samples were subjected to DENG and CHIK immunoglobulin G (IgM) enzyme-linked immunosorbent assay (ELISA). RESULTS: The seroprevalence of CHIK was 12.5%. Mono infection of CHIK was 3%, and CHIK and DENG dual infection was 9.5%. Most affected age group in CHIK cases was 46-60 years wherein female preponderance was seen. All 6 patients with CHIK mono-infection had fever and joint involvement; knee and elbow were the most commonly affected joints. All CHIK patients had VAS score of 6-10 with restricted joint movement. Of the patients with dual infection, the majorities were from 31 to 45 years with male preponderance; all had fever and joint pain mainly affecting knee and elbow. Of patients who had VAS score 6-10 in patients with dual infection, only 5.26% had restricted joint movement. CONCLUSION: IgM ELISA for Chikungunya infection should be included in the routine laboratory tests for acute febrile illness. PMID- 27365917 TI - Induced Sputum Nitrite Levels Correlate with Clinical Asthma Parameters in Children Aged 7-18 Years with Mild to Moderate Persistent Asthma. AB - PURPOSE: The objective of this study is to measure levels of nitrites in induced sputum in children with asthma and correlate it with clinical asthma parameters. METHOD: This prospective observational study was done in PGIMER, Dr. Ram Manohar Lohia Hospital, New Delhi, on 91 children aged 7-18 years with mild and moderate persistent asthma. Patients were specifically evaluated for five clinical parameters of asthma (i.e. Days of acute exacerbations, use of salbutamol as rescue medication, emergency visits, nights with cough, days of school absence) and induced sputum nitrite levels was done at the time of enrollment and 3 months after treatment with inhaled budesonide. RESULTS: The mean age of subjects was 10.79 +/- 2.563yrs. Six (6.59%) patients were not able to perform induced sputum, eighty five (93.41%) patients were suitable for data analysis. There was significant reduction in sputum nitrite levels from 33.42 +/- 22.04nmol/ml at enrollment to 11.72 +/- 5.61 nmol/ml (P < 0.0005) after 3 months of inhaled budesonide therapy. Significant positive correlation was found between reduction in sputum nitrite level and control of asthma symptoms: Days of acute exacerbations(r value = 0.548, P value = 0.0001), Days of salbutamol use as rescue medication (r value = 0.431, P value =< 0.0001), Number of emergency visits(r value = 0.414, P value = 0.0001), Nights with cough (r value = 0.259, P value = 0.0169), Days of school absence(r value = 0.411, P value = 0.0001). Sputum nitrite levels were significantly higher in moderate persistent asthmatics as compared to mild at the time of enrollment (P < 0.0005), which shows that induced sputum nitrite levels correlate with asthma severity. CONCLUSIONS: This study confirms that nitrites in induced sputum correlate well with clinical asthma parameters and asthma severity in children and is a simple, non invasive, and cheap method which can be used as a parameter for monitoring of asthma. PMID- 27365918 TI - Epidemiology of Rifampicin Resistant Tuberculosis and Common Mutations in rpoB Gene of Mycobacterium tuberculosis: A Retrospective Study from Six Districts of Punjab (India) Using Xpert MTB/RIF Assay. AB - BACKGROUND: Xpert MTB/RIF assay has revolutionized the diagnosis of tuberculosis (TB) by simultaneously detecting the bacteria and resistance to rifampicin (RIF), a surrogate marker for multidrug-resistant TB (MDR-TB) in <2 h. The RIF resistance pattern in Malwa region of Punjab, India, is not documented. Here, we report the epidemiology of RIF-resistant TB and mutations in rpoB gene of Mycobacterium tuberculosis (MTB). MATERIALS AND METHODS: A total of 1612 specimens received between October 2013 and February 2015 were tested by Xpert MTB/RIF assay following manufacturer's instructions. The results thus obtained were analyzed using SPSS version 20.0.0 (SPSS Inc., Chicago, IL, USA) statistical software. RESULT: RIF resistance was statistically higher in previously treated patients in comparison to the new patients (P = 0.006) and in patients with acid fast-Bacilli (AFB) positive smears to AFB-negative smears (P = 0.048). RIF resistance mutations in 130 specimens revealed frequency of E 73/130 (56%), B 28/130 (21.5%), D 18/130 (13.8%), A 11/130 (8.4%), and C 1/130 (0.7%) while in one specimen, mutation combination, i.e., mutations associated with more than one probe (A and B both) was present. CONCLUSION: Xpert MTB/RIF assay is a user friendly screening tool for detection of MTB and RIF resistance from suspected TB/MDR cases in a shorter period of time. It could also serve as a useful technique to have simultaneous preliminary information regarding the mutation pattern of RIF resistance in MTB isolates. PMID- 27365919 TI - Is There a Tendency for Thrombosis in Gestational Diabetes Mellitus? AB - CONTEXT: Impact of gestational diabetes mellitus (GDM) on the coagulation system, dynamics involved at a pathophysiological level and the exact mechanism remain unclear. AIMS: To evaluate the association between diabetes-related parameters and hemostatic factors to search for a tendency of thrombosis in GDM. SETTINGS AND DESIGN: Nineteen pregnant women who had GDM, 16 healthy pregnant and 13 healthy nonpregnant controls admitted to the Endocrinology outpatient clinics were enrolled in the study. SUBJECTS AND METHODS: Fasting and postprandial glucose, hemoglobin A1c and insulin levels, and insulin resistance; fructosamine, thrombin activatable fibrinolysis inhibitor (TAFI), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor Type-1 (PAI-1), tissue-type plasminogen activator (t-PA), fibrinogen, plasminogen and hemoglobin levels, platelet counts, prothrombin time (PT), and activated partial thromboplastin time (aPTT) were studied. STATISTICAL ANALYSIS USED: One-way analysis of variance, Kruskal-Wallis, and post hoc Tukey honestly significant difference or Conover's nonparametric multiple comparison tests for comparison of the study groups. RESULTS: PT and aPTT were significantly lower in GDM patients compared to controls (P < 0.05), whereas fibrinogen and plasminogen levels were significantly higher in this group compared to both nonpregnant and healthy pregnant controls (P < 0.05 for each). TAFI, TFPI, PAI-1, and tissue t-PA levels were not significantly different among groups. CONCLUSIONS: Our findings indicate tendency to develop thrombosis in GDM similar to diabetes mellitus; but more comprehensive studies with larger sample size are needed to determine the relationship between GDM and hemostasis. PMID- 27365920 TI - Comparison of Microwave Versus Conventional Decalcification of Teeth Using Three Different Decalcifying Solutions. AB - BACKGROUND: In routine histopathology, decalcification of teeth is an essential and important step during tissue processing. The present study was attempted to decalcify teeth using microwave method and to compare it with conventional decalcification method. AIM: To compare microwave decalcification with conventional decalcification method with respect to the speed of decalcification, preservation of tissue structure, and efficacy of staining. MATERIALS AND METHODS: A total of 72 single-rooted premolars were used for both conventional and microwave decalcification methods. Three different types of decalcifying agents at 5% and 7% were used. Decalcifying agents included nitric acid, formic acid, and trichloroacetic acid, each at 5% and 7%. About 6 teeth were included in each category and were decalcified by both conventional and microwave method. After decalcification, all the teeth were examined macroscopically and microscopically. Cramer's V-test was used to determine the statistical significance. RESULTS: The results have shown that microwave method using 5% and 7% nitric acid were the fastest. Structural details and good staining characteristics were better in teeth decalcified by 5% nitric acid and 5% trichloroacetic acid by both the methods. CONCLUSIONS: 5% nitric acid by microwave method proved to be the best decalcifying agent as it was fast and gave good structural details and staining characteristics. PMID- 27365921 TI - Sertoliform Endometrioid Tumor of Ovary Presenting as Torsion. AB - Sertoliform endometrioid carcinoma of the ovary (SEC) is an uncommon variant that bears histologic similarity to sertoli and sertoli-leydig cell tumors. We report an interesting case of SEC in a 55-year-old female with a left ovarian mass with torsion. Histology revealed an SEC, featuring foci of typical endometrioid carcinoma, and areas composed of uniform, small, hollow tubules lined by columnar cells with apical cytoplasm. Tumor cells were strongly immunoreactive for EMA and cytokeratin but negative for inhibin; thus, confirming the diagnosis of SEC ovary. Recognition of this tumor is important as it is a well-differentiated, low grade malignancy that displays good prognosis when confined to the ovary. PMID- 27365922 TI - Hemoglobin E Hemoglobinopathy in an Adult from Assam with Unusual Presentation: A Diagnostic Dilemma. AB - Hemoglobin E (HbE) is estimated to affect at least one million people around the world. Carrier frequency of hemoglobin E/beta-thalassemia (HbE/beta-thalassemia) is highest in Southeast Asia, reaching as high as 60% in parts of Thailand, Laos, and Cambodia. In the Indian subcontinent, highest frequency is observed in The Northeast regions, but relatively rare in rest of the country. Increasing migration of population from highly affected areas is resulting in rising prevalence in The South and other parts of India. HbE/beta-thalassemia is characterized by marked clinical diversity, phenotypic instability, and age related changes in adaptation to anemia. This paper reports a case of HbE disease in an adult immigrant from Assam and documents the difficulties encountered in the definitive subtyping of HbE hemoglobinopathy. Distinguishing between homozygous HbE disease and HbE/beta-thalassemia is a challenge to hematopathologist as both are clinically and hematologically similar. PMID- 27365923 TI - Sharma's Python Sign: A New Tubal Sign in Female Genital Tuberculosis. AB - Female genital tuberculosis (FGTB) is an important cause of infertility in developing countries. Various type of TB salpingitis can be endosalpingitis, exosalpingitis, interstitial TB salpingitis, and salpingitis isthmica nodosa. The fallopian tubes are thickened enlarged and tortuous. Unilateral or bilateral hydrosalpinx or pyosalpinx may be formed. A new sign python sign is presented in which fallopian tube looks like a blue python on dye testing in FGTB. PMID- 27365924 TI - Xp11.2 Translocation Renal Cell Carcinoma Diagnosed by Immunohistochemistry and Cytogenetics. AB - Xp11.2 translocation renal cell carcinomas (TRCCs) are a group of neoplasms with distinct clinical, histopathological appearance, immunohistochemical, and cytogenetic profile. We report a case of Xp11.2 translocation TRCC in an 11-year old male diagnosed based on immunohistochemistry and fluorescence in situ hybridization. PMID- 27365925 TI - Cholecystitis Associated with Heterotopic Pancreas, Pseudopyloric Metaplasia, and Adenomyomatous Hyperplasia: A Rare Combination. AB - Heterotopic pancreatic tissue in the gall bladder is an uncommon incidental finding in most cases. We hereby describe the case of a 45-year-old woman who presented with symptoms of acalculous cholecystitis. Pathological examination detected heterotopic pancreatic tissue, pseudopyloric metaplasia, and adenomyomatous hyperplasia in the gall bladder. This is a rare combination of three entities which is being reported for the first time. This case emphasizes that heterotopic pancreas might be the causative factor for cholecystitis. PMID- 27365926 TI - Disseminated Histoplasmosis: A Fatal Opportunistic Infection in Disguise. AB - Histoplasma capsulatum is no longer confined to certain geographic areas and should always be considered in the differential diagnosis of lymphadenopathy and organomegaly in HIV-positive patients. We present an unusual case of a 20-year old immunocompromised male of African origin presenting with fever, jaundice, hepatosplenomegaly, and retroperitoneal and cervical lymphadenopathy. Fine needle aspiration (FNA) smears from the cervical lymph node revealed numerous yeast forms of histoplasma in macrophages. The patient succumbed to the fulminant infection. Postmortem liver biopsy also revealed infiltration by histoplasma, confirming the diagnosis of disseminated histoplasmosis. This case highlights the variable nature of the clinical presentation of disseminated histoplasmosis which can mimic tuberculosis, leishmaniasis, or lymphoma. FNA cytology is a rapid, cost effective, and reliable diagnostic tool for early detection and prompt management of histoplasmosis. PMID- 27365927 TI - Comparative Evaluation of the Antimicrobial Properties of Glass Ionomer Cements with and without Chlorhexidine Gluconate. AB - BACKGROUND: Chlorhexidine gluconate is a widely used antimicrobial agent. Adding chlorhexidine and quaternary ammonium compounds to filling materials, such as composite resins, acrylic resins, and glass ionomer cements increases the antibacterial property of restorative materials. This study includes antibacterial property of glass ionomer restorative cements with chlorhexidine gluconate. AIM: The primary objective of our study was to compare the antimicrobial properties of two commercially available glass ionomer cements with and without chlorhexidine gluconate on strains of mutans streptococci. MATERIALS AND METHODS: Two glass ionomers (Fuji II Conventional and Fuji IX) were used. Chlorhexidine gluconate was mixed with glass ionomer cements, and antimicrobial properties against mutans streptococci were assessed by agar diffusion. The tested bacterial strain was inhibited and the antimicrobial properties decreased with time. RESULTS: The highest amount of antimicrobial activity with mean inhibitory zone was found in Fuji II with chlorhexidine gluconate followed by Fuji IX with chlorhexidine gluconate, Fuji II without chlorhexidine gluconate, and Fuji IX without chlorhexidine gluconate. CONCLUSION: The results of the study confirmed that the addition of 5% chlorhexidine gluconate to Fuji II and Fuji IX glass ionomer cements resulted in a restorative material that had increased antimicrobial properties over the conventional glass ionomer cements alone for Streptococcus mutans. How to cite this article: Yadiki JV, Jampanapalli SR , Konda S, Inguva HC, Chimata VK. Comparative Evaluation of the Antimicrobial Properties of Glass Ionomer Cements with and without Chlorhexidine Gluconate. Int J Clin Pediatr Dent 2016;9(2):99-103. PMID- 27365928 TI - Prevalence of Gingival Biotypes among Young Dentate North Indian Population: A Biometric Approach. AB - AIM: To evaluate the prevalence of various gingival biotypes and to corroborate gingival thickness and gingival biotypes across tooth type, site, and gender. MATERIALS AND METHODS: A cross-sectional study was conducted across systemically healthy subjects. A systematic clinical evaluation for gingival biotypes and gingival thicknesses was recorded by modified Iwanson's gauge, to the nearest 0.1 mm, probing the gingival sulcus at the midfacial aspect of maxillary and mandibular central incisors and first molars. All measurements were made across a total of 920 sites in 115 subjects (69 female and 46 male) based on gingival transparency and were statistically analyzed. RESULTS: A significant agreement on the reproducibility of the measurements was noted. The median overall gingival thickness was recorded at 0.75 mm with interquantile difference of 0.39 mm. The thin biotype variant showed across the ranges of 0.3 to 0.6 mm of gingival thicknesses and thick biotype variant across the ranges of 1.0 to 1.2 mm, with more prevalence in anterior and posterior site respectively. Moreover, for gingi val thickness of 0.7 mm, the probe visibility showed tendency toward both thin/thick biotype variant in both anterior and posterior segments. The disposition of male participants toward thick biotype and female participants toward the thin biotype variant has been noted. CONCLUSION: Within the limitations of the current study, our data support the traditional hypothesis of two main gingival biotypes as distinguishable by gingival transparency. In addition, we provide evidence of existence of intermediate biotypes with respect to gingival thickness. These findings can be utilized as objective guidelines for determination of biotype and can be implicated in many dental operative procedures. How to cite this article: Rathee M, Rao PL, Bhoria M. Prevalence of Gingival Biotypes among Young Dentate North Indian Population: A Biometric Approach. Int J Clin Pediatr Dent 2016;9(2):104-108. PMID- 27365930 TI - Comparative Evaluation of the Antibacterial Efficacy of Type II Glass lonomer Cement, Type IX Glass lonomer Cement, and AMALGOMERTM Ceramic Reinforcement by Modified "Direct Contact Test": An in vitro Study. AB - BACKGROUND: Streptococcus mutans (ATCC25175) has a profound effect on the incidence of dental decay in the human population. Many studies have been performed to assess the antimicrobial activity of different cements. However, little or no information is available about the antibacterial properties of Type II glass ionomer cement (GIC), Type IX GIC, and AMALGOMERTM ceramic reinforcement (CR). AIM: To comparatively evaluate the antibacterial activity of Type II GIC, Type IX GIC, and AMALGOMERTM CR by modified direct contact test. MATERIALS AND METHODS: The total sample size was 72 which was divided into four study groups. Six wells were coated by each: Type II GIC, Type IX GIC, AMALGOMERTM CR, and control group (only S. mutans). Statistical analysis was done using analysis of variance and the intergroup comparison was done using post hoc Tukey test. RESULTS: AMALGOMERTM CR was found to have a better antibacterial effect as compared with Type II and IX GIC. CONCLUSION: AMALGOMERTM CR can serve as a valuable cement in pediatric dentistry due to its anticariogenic property. How to cite this article: Hugar SM, Assudani HG, Patil V, Kukreja P, Uppin C, Thakkar P. Comparative Evaluation of the Antibacterial Efficacy of Type II Glass lonomer Cement, Type IX Glass Ionomer Cement, and AMALGOMERTM Ceramic Reinforcement by Modified "Direct Contact Test": An in vitro Study. Int J Clin Pediatr Dent 2016;9(2):114-117. PMID- 27365929 TI - Survival of Composite Resin Restorations of severely Decayed Primary Anterior Teeth retained by Glass Fiber Posts or Reversed-orientated Metal Posts. AB - AIM: The aim of this study was to compare the survival of composite resin restorations retained by glass fiber posts or reversed-orientated (upside-down) metal posts in severely decayed primary anterior teeth after 6, 12, and 18 months. MATERIALS AND METHODS: A total of forty-four 3- to 5-year-old children with bilateral severely decayed primary maxillary canines were included. Patients were treated under general anesthesia. After pulpectomy, an intracanal post was seated in the primary maxillary canine on each side: either a glass fiber post or a metallic post in reversed orientation and teeth restored with light-cured composite. Survival rate of each technique was evaluated at predetermined follow ups and data were analyzed with McNemar's test (alpha = 0.05). RESULTS: The difference in survival of restorations retained by two types of posts was not statistically significant in clinical and radiographical evaluations after 6, 12, and 18 months. The survival rate of reversed-orientated metal and glass fiber posts after 18 months was 81.1 and 67.6% respectively (p = 0.14). CONCLUSION: Reversed-orientated metal post did not show lower clinical survival compared with glass fiber posts in 18-month follow-up. Hence, reversed-orientated metal post can be considered as a potential method to obtain retention for composite restorations in severely decayed primary anterior teeth. How to cite this article: Vafaei A, Ranjkesh B, L0vschall H, Erfanparast L, Jafarabadi MA, Oskouei SG, Isidor F. Survival of Composite Resin Restorations of severely Decayed Primary Anterior Teeth retained by Glass Fiber Posts or Reversed-orientated Metal Posts. Int J Clin Pediatr Dent 2016;9(2):109-113. PMID- 27365931 TI - Comparative Evaluation of Electronic Apex Locators and Radiovisiography for Working Length Determination in Primary Teeth in vivo. AB - AIMS: The aim of this study was to evaluate the effectiveness of two different varieties of electronic apex locators and radiovisiography (RVG) for working length determination in primary teeth. MATERIALS AND METHODS: A total of 30 primary teeth indicated for pulpectomy in children aged 3 to 8 years were randomly selected and subjected to working length determination using two varieties of electronic apex locators and RVG separately. The data were then subjected to statistical analysis. RESULTS: A very strong correlation between electronic measurement methods and RVG length was observed. CONCLUSION: Radiovisiography and apex locators are equally effective in determining working length in primary teeth. How to cite this article: Abdullah A, Singh N, Rathore MS, Tandon S, Rajkumar B. Comparative Evaluation of Electronic Apex Locators and Radiovisiography for Working Length Determination in Primary Teeth in vivo. Int J Clin Pediatr Dent 2016;9(2):118-123. PMID- 27365933 TI - Psychosocial Effects of Fractured Anterior Teeth among Rural Children. AB - AIM: The aim of the study is to determine how rural children view children with visible incisor fracture. MATERIALS AND METHODS: Class 7 (aged 11-12 years) and class 10 (aged 14-15 years) schoolchildren (the participants) were invited to make a social judgment about the color photograph of two children (the subjects). Participants were randomly allocated either (i) pictures of children without incisor fracture or (ii) pictures of the same children whose photographs had been digitally modified to visible incisor fracture. Using a child-centered questionnaire, participants rated subjects using a four-point Likert scale for three negative and six positive attributes. Total attribute scores were tested for significant differences, according to whether the subject had visible incisor fracture or not, using multivariate analysis of variance (p < 0.05). RESULTS: Both class 7 and 10 children rated subjects with visible incisor fracture more negatively than the subjects without incisor fracture. Female participants of class 10 have rated the male subject with incisor fracture significantly negatively (p < 0.01) than male subject without incisor fracture. How to cite this article: Venkatesan R, Naveen M, Teja R, Paulindraraj S, Vallabhaneni SK, Arumugam SB. Psychosocial Effects of Fractured Anterior Teeth among Rural Children. Int J Clin Pediatr Dent 2016;9(2):128-130. PMID- 27365932 TI - Comparison of cleaning Efficacy and Instrumentation Time between Rotary and Manual Instrumentation Techniques in Primary Teeth: An in vitro Study. AB - OBJECTIVES: The aim of this study was to compare the cleaning efficacy and instrumentation time between manual Hedstrom files (H-files) and rotary Mtwo files in primary molar root canals. MATERIALS AND METHODS: A total of 90 primary root canals were selected using standardized radiographs. The canals were injected with India ink with 30 gauge insulin syringe and divided into three groups. Group I-30 root canals instrumented with H-files, group II-30 root canals instrumented with Mtwo files, and group III-control group in which no canal instrumentation was done. The teeth were cleared in various solutions and then observed under a stereomicroscope. RESULTS: No significant difference was seen in cleaning efficacy between H-files and Mtwo files in coronal, middle, and apical thirds of the root canal. The instrumentation time recorded for H-files (3.41 +/- 0.38 minutes) was significantly less than that of Mtwo files (4.81 +/- 0.52). CONCLUSION: Although there was no significant difference in cleaning capacity, further studies should be carried out using the single file systems. How to cite this article: Katge F, Chimata VK, Poojari M, Shetty S, Rusawat B. Comparison of cleaning Efficacy and Instrumentation Time between Rotary and Manual Instrumentation Techniques in Primary Teeth: An in vitro Study. Int J Clin Pediatr Dent 2016;9(2):124-127. PMID- 27365934 TI - Oral Lesions in Neonates. AB - Oral lesions in neonates represent a wide range of diseases often creating apprehension and anxiety among parents. Early examination and prompt diagnosis can aid in prudent management and serve as baseline against the future course of the disease. The present review aims to enlist and describe the diagnostic features of commonly encountered oral lesions in neonates. How to cite this article: Patil S, Rao RS, Majumdar B, Jafer M, Maralingannavar M, Sukumaran A. Oral Lesions in Neonates. Int J Clin Pediatr Dent 2016;9(2):131-138. PMID- 27365935 TI - Lesch-Nyhan Syndrome: Disorder of Self-mutilating Behavior. AB - Lesch-Nyhan syndrome (LNS), a rare inborn error of metabolism, is characterized by self-injurious behavior, which results in partial or total destruction of oral and perioral tissues and/ or fingers. Persistent self-injurious behavior (biting the fingers, hands, lips, and cheeks; banging the head or limbs) is a hallmark of the disease. Prevention of self-mutilation raises significant difficulties. A case of a 10-month-old boy with aggressive behavior and severe lower lip injuries is presented. How to cite this article: Jathar P, Panse AM, Jathar M, Gawali PN. Lesch-Nyhan Syndrome: Disorder of Self-mutilating Behavior. Int J Clin Pediatr Dent 2016;9(2):139-142. PMID- 27365936 TI - Management of feeding Problem in a Patient with Cleft Lip/Palate. AB - In a child with cleft lip and/or palate, nutrition is the first priority as for any other child. These children have specific physical limitations. To fulfill their nutritional requirement, these children need modifications in order to thrive and grow. Failure to adjust to these needs could place the children into a potential life-threatening situation. One of the immediate problems to be addressed in a newborn with cleft lip/palate is difficulty in feeding. Nasal regurgitation and choking are common because of inability of the palate to separate the nasal and oral cavities. The case presented here discusses the management of feeding problem in the infant with cleft lip/palate. How to cite this article: Goswami M, Jangra B, Bhushan U. Management of feeding Problem in a Patient with Cleft Lip/ Palate. Int J Clin Pediatr Dent 2016;9(2):143-145. PMID- 27365937 TI - Cheek Plumper: An Innovative Anti-cheek Biting Appliance. AB - One of the most challenging tasks for a pediatric dentist is the management of deleterious oral habits which adversely affect the dentofacial complex. However, if these habits can be intercepted and diagnosed well in time, they can save the patient from the psychological impact of undergoing long treatment therapies. One such rare deleterious oral habit is cheek biting that affects the buccal mucosa. Presented here is a case report which describes the interception of this deleterious habit in a 15-year-old female child who was a bilateral cheek biter with the help of an innovative intraoral appliance: The cheek plumper. How to cite this article: Rana V, Srivastava N, Kaushik N, Panthri P. Cheek Plumper: An Innovative Anti-cheek Biting Appliance. Int J Clin Pediatr Dent 2016;9(2):146 148. PMID- 27365938 TI - Lipoid Proteinosis. AB - A case report of a 6-year-old male child who reported with recurrent oral and skin ulcerations since childhood and was diagnosed as lipoid proteinosis manifesting with generalized thickening, hardening, and scarring of the skin and hoarseness of voice; is presented here. How to cite this article: Mittal HC, Yadav S, Malik S, Singh G. Lipoid Proteinosis. Int J Clin Pediatr Dent 2016;9(2):149-151. PMID- 27365939 TI - A Novel approach of Esthetic Management and preserving Vitality of Dilacerated Permanent Maxillary Lateral Incisor. AB - Dilaceration of the permanent tooth usually is a consequence of traumatic injuries to the primary teeth. Although it may appear anywhere in the long axis of the tooth, i.e., crown, cementoenamel junction, or root, most often the root is involved. However, crown dilaceration is a rare condition representing 3% of the total injuries. Maxillary incisors are more susceptible to such injury and affected tooth may either erupt buccally or lingually or remain impacted. Hitherto, the treatment options also differ as per the clinical scenario. This article proposes a novel technique of restoring esthetic function of the affected permanent maxillary lateral incisor with crown-root dilaceration while preserving the vitality of tooth. How to cite this article: Achary RC, Ravi GR. A Novel approach of Esthetic Management and preserving Vitality of Dilacerated Permanent Maxillary Lateral Incisor. Int J Clin Pediatr Dent 2016;9(2):152-155. PMID- 27365940 TI - Oral Cysticercosis in a Pediatric Patient: A Rare Case Report with Review. AB - Cysticercosis is a condition in which a human acts as the intermediate host of the pork tapeworm Taenia solium. Although cysticercosis is a common disease in some regions of the world and can occur in any body site, oral lesions are rare. In this report, we document the case of oral cysticercosis in a 10-year-old boy who sought treatment for an asymptomatic nodule on the dorsal surface of the tongue. A detailed history, thorough clinical examination, morphological appearance and the histopathologic findings of the excised cyst formed the basis for the diagnosis of the lesion. How to cite this article: Goenka P, Sarawgi A, Asopa K, Gumber P, Dutta S. Oral Cysticercosis in a Pediatric Patient: A Rare Case Report with Review. Int J Clin Pediatr Dent 2016;9(2):156-161. PMID- 27365941 TI - Validation of Association between Breastfeeding Duration, Facial Profile, Occlusion, and Spacing: A Cross-sectional Study. AB - INTRODUCTION: This cross-sectional retrospective study was designed to assess the relationships among breastfeeding duration, nonnutritive sucking habits, convex facial profile, nonspaced dentition, and distoclusion in the deciduous dentition. MATERIALS AND METHODS: A sample of 415 children (228 males, 187 females) aged 4 to 6 years from a mixed Indian population was clinically examined by two orthodontists. Information about breastfeeding duration and nonnutritive sucking habits was obtained by written questionnaire which was answered by the parents. RESULTS: Chi-square test did not indicate any significant association among breastfeeding duration, convex facial profile, and distoclusion. Statistically significant association was observed between breastfeeding duration and nonspaced dentition and also between breastfeeding duration and nonnutritive sucking habits. Nonnutritive sucking habits had a statistically significant association with distoclusion and convex facial profile (odds ratio 7.04 and 4.03 respectively). Nonnutritive sucking habits did not have a statistically significant association with nonspaced dentition. CONCLUSION: The children breastfed < 6 months had almost twofold increased probability for developing sucking habits and nonspaced dentition, respectively, than the children who had breastfeeding > 6 months duration. It can also be hypothesized that nonnutritive sucking habits may act as a dominant variable in the relationship between breastfeeding duration and occurrence of convex facial profile and distoclusion in deciduous dentition. How to cite this article: Agarwal SS, Sharma M, Nehra K, Jayan B, Poonia A, Bhattal H. Validation of Association between Breastfeeding Duration, Facial Profile, Occlusion, and Spacing: A Cross-sectional Study. Int J Clin Pediatr Dent 2016;9(2):162-166. PMID- 27365942 TI - Molar Incisor Hypomineralization: An Epidemiological Study with Prevalence and Etiological Factors in Indian Pediatric Population. AB - AIMS: To determine the prevalence of molar incisor hypomineralization (MIH) in Indian children and to analyze the possible etiological factors. MATERIALS AND METHODS: First permanent molars and all permanent incisors were examined in 1,369 children aged 8 to 12 years. Examinations were performed by two calibrated observers. The subjects were evaluated using judgment criteria proposed by Weerheijm et al in 2003. The parents accompanying children were given a questionnaire regarding pre- and postnatal history of the children. RESULTS: A total of 191 children were diagnosed with MIH with a prevalence of 13.9%. Chi square/Fisher exact test was used to compare the dichotomous variables. The relative risk with its 95% confidence interval was calculated to find the risk of clinical infections, such as chicken pox, jaundice, renal disorders, cardiac disorders, and affected molars with sex and type of delivery. Pre- and postnatal history of infection in a child was significantly correlated with the prevalence of MIH. CONCLUSION: The prevalence of MIH was 13.9% in the age group of 8 to 12 years. Prenatal and postnatal infections play an important role in hypomineralization of molars and incisors. How to cite this article: Mishra A, Pandey RK. Molar Incisor Hypomineralization: An Epidemiological Study with Prevalence and Etiological Factors in Indian Pediatric Population. Int J Clin Pediatr Dent 2016;9(2):167-171. PMID- 27365943 TI - Knowledge, Attitudes, and Oral Health Practices of School Children in Davangere. AB - AIMS: The aim of this study was to assess the knowledge, attitude, and behavior of school children towards oral health. SETTINGS AND DESIGN: Descriptive study. MATERIALS AND METHODS: School children (n=700) aged between 10 to 14 years in a Davangere school were recruited into this study. The subjects completed a questionnaire that aimed to evaluate young school children's behavior, knowledge, and perception of their oral health and dental treatment. STATISTICAL ANALYSIS: The results were statistically analysed and percentage was calculated. RESULTS AND CONCLUSION: The participant oral hygiene habits (such as tooth brushing) were found to be irregular, and parent role in the oral hygiene habits of their children was limited. The study population showed higher awareness of caries than periodontal conditions. The children in this study also recognized the importance of oral health. The results of this study indicate that Comprehensive oral health educational programs for both children and their parents are required to achieve this goal. How to cite this article: Vishwanathaiah S. Knowledge, Attitudes, and Oral Health Practices of School Children in Davangere. Int J Clin Pediatr Dent 2016;9(2):172-176. PMID- 27365945 TI - Guest Editorial. PMID- 27365944 TI - Knowledge and Awareness among Parents and General Dental Practitioners regarding Rehabilitation with Full Coverage Restoration in Children: A Multi-centric Trial. AB - AIMS: The aim of this study was to evaluate the knowledge and awareness among parents and general dental practitioners regarding rehabilitation with full coverage restoration in children following pulp therapy. MATERIALS AND METHODS: A multiple choice questionnaire was given to 1,000 parents and 400 general practitioners in this multicentric trial. The questionnaire assessed their beliefs, knowledge regarding care of primary teeth, assessment of treating children, and knowledge regarding importance of primary teeth. All the questionnaires were then compiled and statistically analyzed using Statistical Package for Social Sciences (SPSS) software. RESULTS AND DISCUSSION: 53% parents did not know the importance of primary teeth and 73% parents also thought that no treatment is possible for pulpally involved primary teeth. 20% parents believed that root canal treatment can be possible for children and only 10% knew about full coverage restorations. 40% of the general dentists felt that the best treatment in the case of primary necrotic teeth is extraction and only 13% knew about stainless steel crowns. 62% of general dental practitioners pointed out patients' noninterest in providing crowns whereas 68% parents reported non information by dentists. CONCLUSION: Both parents and general dental practitioners have incomplete and inadequate knowledge regarding full coverage restorations, and we need to improve the knowledge and dental awareness of the parents and the general dental practitioners. How to cite this article: Moda A, Saroj G, Sharma S, Gupta B. Knowledge and Awareness among Parents and General Dental Practitioners regarding Rehabilitation with Full Coverage Restoration in Children: A Multi-centric Trial. Int J Clin Pediatr Dent 2016;9(2):177-180. PMID- 27365946 TI - Temozolomide therapy: Focus on patients with pituitary carcinoma. PMID- 27365947 TI - Importance of medial antebrachial cutaneous nerve anatomical variations in upper arm surgery. PMID- 27365948 TI - Knowledge, attitude, and practice of people toward epilepsy in a South Indian village. PMID- 27365949 TI - Malnutrition as a cause of mental retardation: A population-based study from Sub Himalayan India. AB - BACKGROUND: Mental retardation is one of the most common disabilities of childhood. The research on childhood malnutrition and its relationship with cognitive functioning suggests that malnutrition alone does not cause mental retardation. OBJECTIVE: To identify the relation between malnutrition and cognition among children from a Sub-Himalayan state in North India. MATERIALS AND METHODS: A two-phase cross-sectional study was conducted in the rural, urban, and slum area of district Kangra. A 30-cluster sampling technique was used to screen a population of children 1-10 years of age from five randomly selected panchayats (village government units) of district Kangra. The screening was based on a modified version of the ten questions screen, adapted to the local population. In the first phase, a door-to-door survey was done to identify suspects of mental retardation. In the second phase, the children found positive in the first phase were called for clinical examination to confirm mental retardation. Anthropometric assessment of all study children was done by measuring weight and height. The nutritional assessment was done by categorizing them according to Waterlow classification for malnutrition. RESULTS: Out of the total 5300 children, 1.7% were diagnosed as mentally retarded. No positive association was reported with different types of malnutrition and mental retardation. A weakly positive association existed between nutritional status and mental retardation (correlation coefficient-0.04). Children who were both wasted and stunted had the highest risk (odds ratio, 95% confidence interval - 5.57, 2.29-10.36) of mental retardation as compared to normal. CONCLUSION: Malnutrition may be one of the causes but certainly not the only cause of mental retardation. Other causes may be contributing more significantly toward it. PMID- 27365950 TI - Morphological spectrum of peripheral nerve sheath tumors: An insight into World Health Organization 2013 classification. AB - INTRODUCTION: Peripheral nerve sheath tumors (PNSTs) are neuroectodermal in origin. Now these tumors are classified under World Health Organization (WHO) classification of tumors of soft tissue and bone 2013. OBJECTIVE: To study the morphological spectrum of PNST and to study the secondary degenerative changes associated with it. MATERIALS AND METHODS: This study was conducted from January 2010 to June 2015. The gross details of tumor and patient's demographic profiles were reviewed. The hematoxylin and eosin stained slides were reassessed and the lesions were categorized and classified as per the WHO 2013 classification. The tumors were also assessed for secondary degenerative changes. RESULTS: Our study comprised 143 cases of PNST. Age of the patients ranged from 5 to 75 years. 21-30 years is the most common age of occurrence with head and neck being the most common site. The PNSTs observed in the present study were neurofibroma (NF) (61.5%), schwannoma (36%), malignant PNST (2%), and granular cell tumor (0.5%). Nearly 10% of NF fulfilled the criteria for neurofibromatosis 1 (NF1). Rare tumors such as plexiform schwannoma and granular cell tumor were also observed. Malignant tumors were larger in dimension than benign. Myxoid, cystic, and hyaline changes were commonly associated with benign tumors while necrosis, hemorrhage, and mitotic activity were seen with malignant tumors. CONCLUSION: This series highlights the pathological variants of PNST along with their morphological changes and NF1 association. It is essential to be familiar with all these variants of PNST for accurate diagnosis as they have varied biological behavior. PMID- 27365951 TI - Quality of life of cerebral palsy patients and their caregivers: A cross sectional study in a rehabilitation center Khartoum-Sudan (2014 - 2015). AB - BACKGROUND: Cerebral palsy (CP) is group of disorders characterized by long-term disabilities that affect the quality of life (QoL) of both patients and those caring for them. OBJECTIVE: The objective of this study was to measure the QoL of CP patients and their caregivers and determine the factors affecting both of them. METHODS: This was a cross-sectional facility-based study. 65 caregivers of children with CP aged 4-18 years completed a self-structured questionnaire. Descriptives of the samples were displayed, and logistic regression was used in the analysis. RESULTS: The scores of overall QoL of both children and caregivers were low, however, variations were observed among different domains. Both health related and sociodemographic factors were found to affect the QoL of children and caregivers. The increase in the degree of disability and presence of complications decreased the children QoL while the availability of health insurance improved it. Whereas the QoL of the caregiver was affected by his/her occupation, the degree of child disability did not affect it. CONCLUSIONS: This study showed that many feasible changes can be adopted to improve the QoL of CP patients and their caregivers. PMID- 27365952 TI - Effect of Vitamin B12 and folic acid supplementation on neuropsychiatric symptoms and immune response in HIV-positive patients. AB - BACKGROUND: Micronutrients such as B12 and folic acid deficiencies are found in higher number in HIV-infected patients. OBJECTIVE: We conducted a study to examine the effect of Vitamin B12 and folic acid supplementation on neuropsychiatric manifestations, CD4 count, and anthropometric measurements in HIV-positive patients. MATERIALS AND METHODS: Three different groups of HIV patients, namely, HIV patients with tuberculosis, HIV patients with neuropsychiatric manifestations, and asymptomatic HIV patients with 50 patients in each group were included in the study. Baseline and follow-up CD4 count, anthropometric measurements, neuropsychiatric assessments, Vitamin B12, and folic acid estimation were done. RESULTS: The prevalence of folic acid deficiency was 27.1% in Group I, 31.9% in Group II, and 23.4% in Group III. The prevalence of Vitamin B12 deficiency was 8.16% in Group I, 6.12% in Group II, and 4.16% in Group III. HIV patients with neuropsychiatric manifestations were noted to have the lowest mean mini-mental score. After the supplementation of vitamins, anthropometric measurements, MMSE as well as Hamilton depression scores, improved in all the three groups whereas Hamilton anxiety scores improved only in Group III. The CD4 count also improved in Groups I and II after the supplementation of vitamins. CONCLUSION: Folic acid deficiency was highest among neuropsychiatric patients. The majority of people who had a folic acid deficiency have shown improvement in their neuropsychiatric assessment scores as well as CD4 count after its supplementation. PMID- 27365953 TI - Evaluation of low back pain with low field open magnetic resonance imaging scanner in rural hospital of Southern India. AB - BACKGROUND: Low back pain (LBP) is the most common symptom which is associated with limitation of normal activities and work-related disability. Imaging techniques are often essential in making the correct diagnosis for prompt management. Plain Radiography though remain a first imaging modality, magnetic resonance imaging (MRI) due to its inherent softtissue contrast resolution and lack of ionizing radiation remains invaluable modality in the evaluation of LBP. AIM: To find the common causes of LBP in different age groups and the role of MRI in detecting the spectrum of various pathological findings. MATERIALS AND METHODS: This is a prospective study done in the Department of Radiodiagnosis during a period of 2 years from July 2013 to July 2015. The study population includes all the cases referred to our department with complaints of LBP. Patients with ferromagnetic metallic implants and uncooperative cases were excluded. HITACHI 0.4 Tesla open MRI machine was used for imaging. RESULTS AND CONCLUSION: This study involved a total of 235 cases. There were 121 males and 114 females. The age of the patient ranged from 21 to 68 years with an average of 41.3 years. Back pain was commonly observed in the third to fifth decade. The common causes for back pain are disc herniations (disc bulge - 35.3%, disc protrusion - 39.6%, disc extrusion - 7.2%) accounting to 82.1%, followed by normal study (10.2%), vertebral collapse (traumatic - 2.1%, osteoporotic - 1.7%), infections (2.1%), and neoplasm (1.7%). MRI provides valuable information regarding the underlying causes of LBP, especially in disc and marrow pathology. PMID- 27365954 TI - Knowledge, attitude, and practice of people toward epilepsy in a South Indian village. AB - INTRODUCTION: People living with epilepsy continue to suffer from enacted or perceived stigma that is based on myths, misconceptions, and misunderstandings that have persisted for many years. In the last decade, there has been an increase in individual literacy rate and increased access to technology in rural population. However, it is unclear if this has any effect on knowledge, attitude, and practice (KAP) attitude toward epilepsy. OBJECTIVE: Our primary aim is to evaluate KAP toward epilepsy. In addition, we also estimated the prevalence of stroke and epilepsy in rural South India. MATERIALS AND METHODS: Using a 14-item questionnaire, we assessed KAP toward epilepsy and identified determinants of inappropriate attitudes toward people with epilepsy and 10-item questionnaires to assess the prevalence of epilepsy and stroke among 500 randomly selected populations in a Pattaravakkam village (Tamil Nadu, India). RESULTS: About 87.7% of the people had heard or read about epilepsy. Negative attitudes appeared to be reinforced by beliefs that epilepsy is hereditary (23.1%), kind of insanity (22.6%), or as contagious (12.0%). The knowledge about the clinical characteristics and first aid to a person during a seizure was 25.8%. About 36.5% of people think that society discriminates people with epilepsy. Moreover, our prevalence study showed that 8.7% people are suffering from epilepsy and 3.7% had stroke previously and at the day of survey, the stroke prevalence is 3.3%. CONCLUSION: Even with increased literacy, technology, and communication devices, the KAP of people toward epilepsy is relatively low. General public education campaigns and specific school education campaigns children should be encouraged to increase the KAP toward epilepsy. The prevalence and pattern of epilepsy and stroke is on the higher side in the village of Pattaravakkam. Future research regarding the value of targeted education in improving KAP will be worthwhile. PMID- 27365956 TI - Commentary. PMID- 27365955 TI - Incidence, histopathology, and surgical outcome of tumors of spinal cord, nerve roots, meninges, and vertebral column - Data based on single institutional (Sher i-Kashmir Institute of Medical Sciences) experience. AB - CONTEXT: In the absence of a community-based study on the spinal tumors in the Valley, medical records of the only Regional Neurosurgical Center are available. AIM: The aim of this study is to establish a hospital-based regional epidemiology of spinal tumors in the Valley since the data are derived from a single institution. MATERIALS AND METHODS: A retrospective analysis of 531 malignant and nonmalignant tumors of spinal cord, its coverings and vertebrae, which were managed in a Regional Neurosurgical Center under a standard and uniform medical protocol over 30-year period from 1983 to 2014. RESULTS: The hospital-based incidence for all spinal tumors was 0.24/100,000 persons per year. The malignant spinal cord and vertebral tumors comprised 32.58% (173/531) of all tumors, and benign spinal cord and vertebral tumors comprised 67.42% (358/531). The extradural-intradural tumors such as metastatic lesions and primary malignant vertebral tumors were on rise with 16.38% (87/531) cases. The children below 18 years were 5.46% (29/531), of which 55.17% (16/29) were below 9 years. The most common primary bone malignancy was multiple myeloma (54.54% =12/22). Histopathologically, the most common metastatic deposit in the spinal canal was non-Hodgkin's lymphoma (24.61% =16/65). A mortality of 3.20% (17/531) was noted. Recurrences were noted in 4.90% (26/531), and adjuvant therapies were given to 16.38% (87/531) patients. CONCLUSION: The malignant spinal cord and vertebral tumors, especially metastatic deposits, are on rise in elderly population. The surgical outcome, in terms of recovery and spinal stability, of benign tumors, is comparatively better than malignant ones. The study reveals a low regional incidence (hospital-based) of spinal tumors. PMID- 27365957 TI - A clinical study of neurological soft signs in patients with schizophrenia. AB - BACKGROUND AND AIM: Neurological soft signs (NSSs) are "objectively measured, nonlocalizing abnormalities, not related to impairment of a specific brain region, reflecting improper cortical-subcortical and intercortical connections." The possibility of NSS as an endophenotype in schizophrenia has been studied across the globe. We aimed at finding the prevalence of NSS among patients with schizophrenia as well as the associations of NSS between various sociodemographic and illness variables. SUBJECTS AND METHODS: One hundred patients between the age group of 16 and 60 years were serially selected from the inpatient department of a tertiary care hospital who have been diagnosed as a case of schizophrenia according to the International Classification of Diseases version 10 during 1 year period. A semi-structured pro forma was used to collect various demographic as well as illness data, and subjects were clinically evaluated for NSS using neurological evaluation scale. RESULTS: The prevalence of NSSs was found to be 67%, significant association was found between NSS and age, occupation, and duration of illness. A statistically significant correlation was found between NSS and age, NSS and duration of illness. CONCLUSION: The validity of NSS as an endophenotype lies in the fact that it should be independent of all sociodemographic and illness variables. However, our study evaluated some statistically significant findings between them. Hence, further researches are required with properly adjusted controls to find if the associations obtained between NSS and different variables here are true or whether there are some confounding factors included. PMID- 27365958 TI - Tubercular meningitis in children: Clinical, pathological, and radiological profile and factors associated with mortality. AB - CONTEXT: Childhood tuberculosis is a major public health problem in developing countries with tubercular meningitis being a serious complication with high mortality and morbidity. AIM: To study the clinicopathological as well as radiological profile of childhood tuberculous meningitis (TBM) cases. SETTINGS AND DESIGN: Prospective, observational study including children <14 years of age with TBM admitted in a tertiary care hospital from Western India. SUBJECTS AND METHODS: TBM was diagnosed based on predefined criteria. Glassgow coma scale (GCS) and intracranial pressure (ICP) was recorded. Staging was done as per British Medical Council Staging System. Mantoux test, chest X-ray, cerebrospinal fluid (CSF) examination, neuroimaging, and other investigations were done to confirm TB. STATISTICAL ANALYSIS USED: STATA software (version 9.0) was used for data analysis. Various risk factors were determined using Chi-square tests, and a P< 0.05 was considered significant. RESULTS: Forty-seven children were included, of which 11 (24.3%) died. Fever was the most common presenting symptom, and meningismus was the most common sign. Twenty-nine (62%) children presented with Stage III disease. Stage III disease, low GCS, and raised ICP were predictors of mortality. Findings on neuroimaging or CSF examination did not predict mortality. CONCLUSIONS: Childhood TBM presents with nonspecific clinical features. Stage III disease, low GCS, lack of Bacillus Calmette-Guerin vaccination at birth and raised ICP seem to the most important adverse prognostic factors. PMID- 27365959 TI - A community-based case-control study of prevalence and pattern of cognitive impairments in patients with epilepsy residing in South-Eastern Nigeria. AB - BACKGROUND: Epilepsy is the commonest neurological disorder encountered in Sub Saharan Africa. The quality of life of patients with epilepsy (PWEs) is adversely affected by cognitive impairments. AIM: This study investigated the prevalence and pattern of cognitive impairments in PWE in Ukpo community located in a South Eastern state in Nigeria using Community Screening Interview for Dementia (CSID) and a computer-assisted cognitive test battery (FePsy). METHODS AND PATIENTS: Fifty-one PWEs were studied and compared with 51 age-, sex-and level of education matched healthy controls. Diagnosis of epilepsy was confirmed clinically with eye witness corroboration. Sociodemographic data and information on epilepsy variables were obtained with the aid of a questionnaire. Cognitive domains assessed include language, memory, orientation, attention, psychomotor speed and constructional praxis. RESULTS: The prevalence rate of cognitive impairment using total CSID score was 19.6%. Analysis of CSID scores revealed significant impairment in language (17.6%), memory (29.4%), orientation (15.7%), attention (7.8%) and constructional praxis (15.7%) compared to healthy controls. A similar pattern was observed with FePsy but with better sensitivity indices for detecting cognitive impairment. CONCLUSION: This study indicated significant prevalence rate of cognitive impairment among treatment-naive PWE with profound affectation of memory, mental speed and language. In addition, the FePsy was found to be more sensitive and specific in assessment of cognitive function in PWE. PMID- 27365961 TI - Dementia in a tribal landlocked elderly population at high altitude: What explains the lower prevalence? AB - INTRODUCTION: Studies across the populations have suggested that dementia is differentially distributed with a lower prevalence in developing regions than the developed ones. A comparison in the prevalence of dementia across populations may provide an insight into its risk factors. Earlier, we reported on the prevalence of dementia in elderly population in migrant, urban, rural, and tribal populations. The present study was conducted with a view to estimating the prevalence of dementia in Tribal Landlocked Elderly Population at high altitude and therefore to draw some conclusions on the differential distribution of dementia across populations. METHODS: A cross-sectional comprehensive two-phase survey of all residents aged 60 years and older was conducted. Phase 1 involved screening of all individuals aged 60 and above with the help of a cognitive screen specifically developed for the tribal population. Phase 2 involved clinical examination of individuals who were suspected of dementia as per the developed cognitive screening test. RESULTS: The results revealed that six individuals out of a total of 481 studied above 60 years of age in the studied population scored between 17 and 23, thus qualifying as suffering from mild cognitive impairment. Importantly, none of the individuals above 60 years of age scored <17. DISCUSSION: The current study is in conformity with our previous study conducted on urban, rural, and migrant areas of the state of Himachal Pradesh again emphasizing on dementia being rare in tribal populations and thereby pointing to the presence of some protective factors among tribal people. PMID- 27365960 TI - Current understandings about cognition and the neurobiological correlates in schizophrenia. AB - Schizophrenia is a severe mental disorder. Cognitive deficits are one of the core features of schizophrenia. Multiple domains of cognition (executive function, attention/vigilance, working memory, verbal fluency, visuospatial skills, processing speed, and social cognition) are affected in patients with schizophrenia. Deficits in cognition led to impairment in the real world functioning. Identifying the cognitive deficits and early intervention is required for better functional outcome. This review focuses on conceptual understanding of cognition with its neurobiological correlates in schizophrenia and its different clinical implications. PMID- 27365962 TI - Deadly intracranial bleed in patients with dengue fever: A series of nine patients and review of literature. AB - INTRODUCTION: Dengue fever is a global pandemic threat with increasing incidence. To date, there are no cures and the effectiveness of dengue vaccines is still uncertain. World Heath Organization introduced expanded dengue syndrome to include unusual presentations of dengue fever including severe neurologic complications. One of the deadly complications is intracranial hemorrhage (ICH). METHODOLOGY: We collected data of patients with ICH diagnosed via a plain computed tomography of the brain (CT brain) with thrombocytopenia and positive Dengue virus type 1 nonstructural protein (NS1) antigen test or positive dengue serology IgM from January 2014 till June 2015 at our center. Nine patients were included and all 20 other remaining patients reported in literature so far are discussed. DISCUSSION: We found that all patients in our center requiring neurosurgical intervention died. Another interesting observation is that detection of Dengue IgG usually meant more severe ICH and poorer outcomes. From our series, platelet levels did not seem to influence the outcome. CONCLUSION: We recommend that for early detection of ICH, Dengue IgG should be routinely screened and a high index of suspicion be maintained. Future research should be focused on determining predictors of ICH in patients with dengue fever so that preventive steps can be taken as mortality is high and no treatment seems beneficial at the moment once severe ICH occurs. PMID- 27365963 TI - Assessment of intracranial metastases from neuroendocrine tumors/carcinoma. AB - BACKGROUND: The most common sites of origin for neuroendocrine carcinoma are gastrointestinal tract and its accessory glands, and lungs. MATERIALS AND METHODS: One-hundred fifty cases diagnosed with metastatic brain lesions were retrieved from hospital records within 5 years. For these cases, the primary neoplasm, histopathological classification, metastasis, treatment, and fate all were studied. RESULTS: Intracranial deposits were detected in 10%. The primary lesion was in the lungs in 87% of patients, and 1 patient in the breast and 1 in esophagus. Pathological classification of the primary lesion was Grade 2 (MIB-1: 3-20%) in 1 patient and neuroendocrine carcinoma (MIB-1: >=21%) in 14 patients. The median period from onset of the primary lesion up to diagnosis of brain metastasis was 12.8 months. About 33% of patients had a single metastasis whereas 67% patients had multiple metastases. Brain metastasis was extirpated in 33% of patients. Stereotactic radiotherapy alone was administered in 20% of patients, and brain metastasis was favorably controlled in most of the patients with coadministration of cranial irradiation as appropriate. The median survival period from diagnosis of brain metastasis was 8.1 months. CONCLUSION: Most of patients with brain metastasis from neuroendocrine carcinoma showed the primary lesion in the lungs, and they had multiple metastases to the liver, lymph nodes, bones, and so forth at the time of diagnosis of brain metastasis. The guidelines for accurate diagnosis and treatment of neuroendocrine carcinoma should be immediately established based on further analyses of those patients with brain metastasis. PMID- 27365964 TI - Subarachnoid hemorrhage due to ruptured intracranial aneurysm following posterior reversible encephalopathy syndrome. AB - Although posterior reversible encephalopathy syndrome (PRES) is rarely associated with subarachnoid hemorrhage, to our knowledge, rupture of a concomitant cerebral aneurysm following PRES has not been reported. We describe a patient with atypical PRES involving the brainstem, thalamus, and periventricular white matter without cortical or subcortical edema of the parietooccipital lobe on magnetic resonance imaging, with rupture of a concomitant cerebral aneurysm. Preexisting extremely high blood pressure may trigger atypical PRES, and failure to lower blood pressure may lead to a concomitant aneurysm rupture. In the future treatment of hypertensive urgency with a recurrence of symptoms and mean arterial blood pressure >150 mmHg, it is advisable to immediately hospitalize the patient for aggressive blood pressure management, especially if PRES is suspected based on clinical and radiological features. PMID- 27365965 TI - Brachial branches of the medial antebrachial cutaneous nerve: A case report with its clinical significance and a short review of the literature. AB - The medial antebrachial cutaneous nerve (MACN) is a branch of the brachial plexus with a great variation within its branches. Knowledge of these variations is critical to neurologists, hand surgeons, plastic surgeons, and vascular surgeons. The aim of this study was to search for variations of the MACN and to discuss their clinical significance. For this study, six arm cadavers from three fresh cadavers were dissected and examined to find and study possible anatomical variations of the MACN. The authors report a rare case of a variation of the MACN, in which there are four brachial cutaneous branches, before the separation to anterior (volar) and posterior (ulnar) branch, that provide sensory innervation to the medial, inferior half of the arm, in the area that is commonly innervated from the medial brachial cutaneous nerve. To our knowledge, this is the first documented case of this nerve variation. This variation should be taken into serious consideration for the differential diagnosis of patients with complaints of hypoesthesia, pain, and paresthesia and for the surgical operations in the medial part of the arm. PMID- 27365966 TI - White matter changes in Wilson's disease: A radiological enigma. AB - Wilson's disease is a metabolic disorder which presents with hepatitis or hepatic decompensation commonly. Neurologic manifestations are late and include movement disorders, personality changes, and seizures. Magnetic resonance imaging (MRI) brain shows high signal changes in putamen, lentiform nucleus, thalamus, and brainstem. White matter lesions are rare. We report a child of Wilson's disease who presented to us with dystonia, rigidity, myoclonus and had symmetrical white matter changes in the fronto-parietooccipital region. Diffusion restriction in bilateral frontoparietal areas was also seen which is rare in chronic cases like ours. Atypical MRI characteristics should be considered in patients with clinical signs of neurological involvement in Wilson's disease as it is a devastating but treatable disease. PMID- 27365968 TI - High-voltage electrocution causing bulbar dysfunction. AB - Electrical shock can result in neurological complications, involving both peripheral and central nervous systems, which may present immediately or later on. High-voltage electrical injuries are uncommonly reported and may predispose to both immediate and delayed neurologic complications. We report the case of a 68-year-old man who experienced a high-voltage electrocution injury, subsequently developed bulbar dysfunction and spontaneously recovered. We describe the development of bulbar palsy following a significant electrical injury, which showed no evidence of this on magnetic resonance imaging. High-voltage electrocution injuries are a serious problem with potential for both immediate and delayed neurologic sequelae. The existing literature has no reports on bulbar dysfunction following electrocution, apart from motor neuron disease. PMID- 27365967 TI - Colistin and tigecycline for management of external ventricular device-related ventriculitis due to multidrug-resistant Acinetobacter baumannii. AB - Acinetobacter baumannii is an important cause of nosocomial ventriculitis associated with external ventricular device (EVD). It is frequently multidrug resistant (MDR), carries a poor outcome, and is difficult to treat. We report a case of MDR Acinetobacter ventriculitis treated with intravenous and intraventricular colistin together with intravenous tigecycline. The patient developed nephrotoxicity and poor neurological outcome despite microbiological cure. Careful implementation of bundle of measures to minimize EVD-associated ventriculitis is valuable. PMID- 27365969 TI - A rare case of parietal bone hemangioma. PMID- 27365970 TI - Infantile desmoplastic astrocytoma: Magnetic resonance imaging suggestive of pathology. PMID- 27365971 TI - Pineal region pilocytic astrocytoma; an unusual site with variable radiological, clinical, and histological features: A report of two cases. PMID- 27365972 TI - A single center study of epidemiology of neural tube defects. PMID- 27365973 TI - Neuroimaging and clinical presentation of stroke developing concurrently with herpes zoster. PMID- 27365974 TI - Spinal extradural arachnoid cyst: A rare cause of neurogenic bladder. PMID- 27365975 TI - Magnetic resonance imaging of brain findings in hyperammonemic encephalopathy. PMID- 27365976 TI - Responding to the challenge of autism spectrum disorder in low-resource settings. PMID- 27365977 TI - Classical case of late-infantile form of metachromatic leukodystrophy. PMID- 27365978 TI - Bridging the epilepsy treatment gap in low- and middle-income nations. PMID- 27365979 TI - Meningoencephalitis, myositis, and rash-neurological presentation of Indian tick typhus. PMID- 27365980 TI - Acute hemichorea-hemiballism as a sole manifestation of acute thalamic infarct: An unusual occurrence. PMID- 27365981 TI - Efficacy of Oral Curcuminoid Fraction from Curcuma xanthorrhiza and Curcuminoid Cider in High-cholesterol Fed Rats. AB - BACKGROUND: Hypercholesterolemia is one of the most important risk factors for atherosclerosis and subsequent cardiovascular diseases. OBJECTIVE: The present work was aimed to study the efficacy of curcuminoid fraction from Curcuma xanthorrhiza and its curcuminoid cider in reducing blood cholesterol level and four genes related to oxidative stress, including cluster of differentiation 44 (CD44), intercellular adhesion molecule 1 (ICAM-1), inducible nitric oxide synthase (iNOS), and lectin-like oxidized low-density lipoprotein receptor-1 (LOX 1) in high-cholesterol fed rats in vivo. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley rats were divided into six groups, namely normal group diet, high cholesterol diet (HCD) 2%, HCD + 100 mg/kg b.w. curcuminoid fraction, HCD + 300 mg/kg b.w. curcuminoid fraction, HCD + cider 1% v/v, and HCD + curcuminoid cider 2% v/v for 4 weeks. Total cholesterol levels were measured at day 1, 14, and 28. Vascular tissues and organs from lung and liver were collected for RNA extraction, followed by quantitative analysis using real-time polymerase chain reaction (PCR). RESULTS: Our results demonstrated that among all the treatment groups, curcuminoid cider at 2% v/v significantly lowered total cholesterol level compared to those of positive control. Real-time PCR data showed both curcuminoid fractions (100 and 300 mg/kg) and curcuminoid cider (1 and 2% v/v) inhibited the gene expression of CD44, ICAM-1, iNOS, and LOX-1, indicating their hypocholesterolemic effects via attenuating genes related to oxidative stress in rats in vivo. CONCLUSION: Oral administration of curcuminoid fraction and its cider product may exert potential inhibitory effects on oxidative stress related genes for preventing hypercholesterolemia-induced atherosclerosis in vivo. SUMMARY: Curcuminoid and its cider significantly inhibited the gene expression of CD44, ICAM-1, iNOS, and LOX-1 in rats in vivoCurcuminoid and its cider suppressed oxidative stress-related genes inducing formation of atherosclerosisCurcuminoid and its cider may offer cardioprotective effect for preventing hypercholesterolemia-induced atherosclerosis Abbreviations Used: ROS: Reactive oxygen species, NO: Nitric oxide, NOS: NO synthase, NADPH: Nicotinamide adenine dinucleotide phosphate, CD44: Cluster of differentiation 44, ICAM-1: Intercellular adhesion molecule 1, iNOS: inducible NOS, LOX-1: lectin-like oxidized LDL receptor-1, HMG-CoA: 3-hydroxy-3-methylglutaryl-coenzyme A, 5-HMF: 5 hydroxymethylfurfural, HCD: High-cholesterol diet. PMID- 27365982 TI - Evaluation of Skin Anti-aging Potential of Citrus reticulata Blanco Peel. AB - BACKGROUND: The peel of Citrus reticulata Blanco is traditionally used as tonic, stomachic, astringent, and carminative. It is also useful in skin care. OBJECTIVE: To study the anti-aging potential of alcoholic extracts of C. reticulata Blanco peel using in vitro antioxidant and anti-enzyme assays. MATERIALS AND METHODS: Plant extracts were obtained by Soxhlation (CR HAE- Hot Alcoholic Extract of Citrus reticulata) and maceration method (CR CAE- Cold Alcoholic Extract of Citrus reticulata). Qualitative and quantitative phytochemical analysis was performed. Further, in vitro antioxidant, anti-enzyme, and gas chromatography-mass spectrometry (GC-MS) analyses were performed. RESULTS: Total phenolic and flavonoid contents of CR HAE were found to be higher than CR CAE. EC50 value of CR HAE and CR CAE for 1,1-Diphenyl-2-picrylhydrazyl, Superoxide anion, and 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) assays were 250.33 +/- 40.16 MUg/ml and 254.73 +/- 15.78 MUg/ml, 221.27 +/- 11.25 MUg/ml and 354.20 +/- 23.79 MUg/ml, and 59.16 +/- 2.17 MUg/ml and 59.12 +/- 6.21 MUg/ml, respectively. Oxygen radical absorbance capacity values for CR HAE and CR CAE were found to be 1243 and 1063 MUmoles 6-hydroxy-2,5,7,8-tetra methylchromane 2-carboxylic acid equivalent/g of substance, respectively. Anti-collagenase and anti-elastase activities were evaluated for both CR HAE and CR CAE. EC50 values of CR HAE and CR CAE for anti-collagenase and anti-elastase were 329.33 +/- 6.38 MUg/ml, 466.93 +/- 8.04 MUg/ml and 3.22 +/- 0.24 mg/ml, 5.09 +/- 0.30 mg/ml, respectively. CR HAE exhibited stronger anti-collagenase and anti-elastase activity than CR CAE. GC-MS analysis of CR HAE was carried out because CR HAE exhibited higher antioxidant and anti-enzyme potential than CR CAE. CONCLUSION: C. reticulata peel can be utilized in anti-wrinkle skin care formulations. SUMMARY: Skin anti-aging potential of Citrus reticulata Blanco peel was evaluated throughIn vitro antioxidant and anti-enzyme assaysTwo types of extraction were performed and extracts were subjected to qualitative and quantitative phytochemical analysis. Extract obtained by Soxhlation (CR HAE) showed higher total phenolic and flavonoid contents than extract obtained by maceration (CR CAE)CR HAE demonstrated strong DPPH and Superoxide free radical scavenging activity whereas, ABTS scavenging activity of both the extracts were found to be similar. Oxygen Radical Absorbance Capacity (ORAC) of CR HAE was found to be more; indicating its strong antioxidant potentialIn vitro collagenase and elastase enzyme inhibition activities were evaluated for both the extracts and CR HAE showed strong anti-collagenase and antielastase potential indicating its anti aging abilityGC-MS analysis of CR HAE revealed the presence of various compounds mainly including Polymethoxyflavones. CR HAE exhibited promising antioxidant and anti-enzymatic activity and can be used as a potent antiwrinkle agent in anti aging skin care formulations. Abbreviation Used: ECM: Extracellular matrix, UV: Ultra violet, ROS: Reactive Oxygen Species, MMP: Matrix metalloproteinase, Chc: Clostridium histolyticum collagenase, DPPH: 2, 2-diphenyl-1-picrylhydrazyl, GC MS: Gas Chromatography-Mass Spectroscopy, RT: Room Temperature, MUg GAE/ mg: Microgram Gallic acid equivalent / milligram, W/V: Weight by Volume, MUg QE/ mg: Microgram Quercetin equivalent / milligram, CR HAE: Hot Alcoholic Extract of Citrus reticulata Blanco, CR CAE: Cold Alcoholic Extract of Citrus reticulata Blanco, EC50: Half Maximal Effective Concentration, PMS NADH: Phenazine methosulfate nicotinamide adenine dinucleotide, NBT: Nitroblue tetrazolium, DMSO: Dimethyl sulfoxide, APS: Ammonium Persulphate, AAPH: 2,2 -azobis(2-amidino propane) dihydrochloride, TROLOX: (+/-) 6-hydroxy-2,5,7,8-tetramethyl chromane-2 carboxylic acid, ORAC: Oxygen Radical Absorbance Capacity, FALGPA: N-[3-(2-Furyl) acryloyl)]-Leu-Gly-Pro-Ala, SANA: Succinyl-Ala-Ala-Ala-p-nitroanilide, Rf: Retardation Factor, MSD: Mass Selective Detector. PMID- 27365983 TI - Assessment of Effectiveness of Barleria prionitis on Oral Health. AB - AIM: To evaluate the efficacy of Barleria prionitis extract mouthwash in comparison with gold standard chlorhexidine (CHX) mouthwash on the oral health. MATERIALS AND METHODS: A total of 30 subjects were randomly divided into two groups, B. prionitis group and the CHX gluconate mouthwash group. The data were collected at the baseline and 3 days. The plaque was disclosed using erythrosine disclosing agent and their scores were recorded using the Quigley and Hein plaque index modified by Turesky-Gilmore-Glickman. Statistical analysis was performed to compare the effect of the two drug regime. RESULTS: Our result showed that the CHX and the B. prionitis were statistically equally effective against dental plaque. Although the action of CHX was more pronounced. CONCLUSIONS: This study has confirmed antimicrobial potential of the plant B. prionitis, thus supporting its folklore application as preventive remedy against oral microbial diseases. SUMMARY: Within the limitation of this trial, herbal mouthwash has been shown to demonstrate similar effects on plaque as compared to the standard drug CHX. Further long term research needs to be done to check the efficacy and effectiveness of herbal products over standard drug regime. PMID- 27365984 TI - Evaluation of Efficacy of Herbal Intrauterine Infusion Uterofix Liquid in Treatment of Various Reproductive Disorders in Cows: A Field Study. AB - OBJECTIVE: To evaluate the efficacy of herbal intrauterine infusion Uterofix liquid in the treatment of various reproductive disorders in cows. MATERIALS AND METHODS: Based on symptoms of endometritis, anestrous, metritis, and repeat breeders, 28 cows were selected to study the efficacy of herbal intrauterine infusion Uterofix liquid (M/S Ayurvet Limited) in uterine infections study. Group T0 (n = 8) cows served as control group, no treatment was given to this group, Group T1 (n = 5) repeat breeder cows, Group T2 (n = 5) endometritis effected cows, Group T3 (n = 5) anoestrus cows, and Group T4 (n = 5) metritis suffered cows were treated with Uterofix liquid (25 ml as intrauterine infusion once a day for 3-5 days). Total observational period was 60 days. Number of treatments needed, nature of discharge in first posttreatment estrus (physical examination), after treatment number of animal showing heat/estrus out of total treated, and posttreatment conception rate were used as criteria to judge the success or failure of treatment. RESULTS: Results revealed that 18 out of 20 animals (90%) showed signs of heat with clear discharge, recovered completely without causing any irritation, or severe irritation/sloughing of genital mucous membrane after Uterofix liquid treatment. CONCLUSION: Herbal intrauterine infusion Uterofix liquid significantly treated the uterine infections in cows. SUMMARY: Uterine infection is a major problem in reproductive management. A wide variety of genital tract diseases of female domestic animals are known to produce significant losses and responsible for poor fertility. Amongst these highly prevalent are metritis and repeat breeding in high-producing dairy cows which if remains untreated are associated with low conception rate per artificial insemination (AI), extended interval to pregnancy, increased culling, and economic losses. As herbal remedy the Uterofix liquid (Ayurvet Limited, India) was highly efficacious as an intrauterine infusion to treat different reproductive disorders. PMID- 27365986 TI - Analgesic and Antioxidant Activities of Stem Bark Extract and Fractions of Petersianthus macrocarpus. AB - BACKGROUND: Petersianthus macrocarpus (Lecythidaceae) is widely used in the folk medicine in Nigeria to relieve pain and fever associated with malaria. This study evaluated the analgesic and antioxidant activities of the methanol extract and fractions of the stem bark of the plant. MATERIALS AND METHODS: The analgesic activity was determined in mice using hotplate and acetic acid-induced writhing models. Morphine sulphate (5 mg/kg, i.p.) and aspirin (100 mg/ml, p.o.) were used as reference analgesic agents. The antioxidant potential was evaluated using 1,1 diphenyl-2-picrylhydrazyl (DPPH) radical; reducing power, iron chelating properties and determination of total phenolic content. RESULTS: The extract at 200 and 500 mg/kg, produced an insignificant (P > 0.05) increase in pain threshold in hotplate but a significant (P < 0.05) increase at 1000 mg/kg. The extract significantly (P < 0.05) reduced the writhing induced by acetic acid in mice in a dose dependent manner. Fractionation increased the analgesic activities significantly (P < 0.05) in ethyl acetate and aqueous fractions (200 mg/kg). The extract demonstrated strong DPPH radical scavenging activity with IC50 0.05 mg/ml, good reducing power and weak iron chelating activities. The total phenol content was 142.32 mg/gin term of gallic acid. The antioxidant effects were more pronounced in ethyl acetate and aqueous fractions. CONCLUSION: The findings of the study suggested that the extract has strong analgesic and antioxidant activities which reside mainly in the polar fractions thus confirming the traditional use of the plant to alleviate pains. SUMMARY: Analgesic and antioxidant activities of extract and solvent fractions of Petersianthus macrocarpus investigated indicated that extract has analgesic and antioxidant properties that reside mainly in the polar fractions. Abbreviations Used: DMSO: Dimethyl sulphoxide, ANOVA: analysis of variance, EDTA: ethylene diamne tetraacetic acid, SDM: standard deviation of mean, PGE: prostaglandins E, PDF: prostaglandins F. PMID- 27365985 TI - Effects of Five Bangladeshi Plant Extracts on In vitro Thrombolysis and Cytotoxicity. AB - BACKGROUND: Piper Betle, Pterospermum acerifolium, Saraca indica, Argyreia speciosa, and Rhaphidophora glauca are medicinal plants commonly used as traditional medicine for the treatment of various diseases. To examine, whether organic extracts of these plants possess thrombolytic properties with minimal or no toxicity is our main aim of the study. MATERIALS AND METHODS: In vitro thrombolytic model was used to check the clot lysis effects using streptokinase (SK) as a positive control and water as a negative control. Cytotoxicity was screened by brine shrimp lethality bioassay using vincristine sulfate (VS) as positive control. RESULTS: Among herbal drugs, different organic extracts of P. betle, P. acerifolium, S. indica, A. speciosa, and R. glauca showed significant (P < 0.05 and P < 0.0001) clot lysis activity viz., 31.58% +/-0.76%, 40.50% +/ 0.94%, 49.70% +/-1.69%, 35.81% +/-0.86%, and 43.80% +/-0.91%, respectively, compared to reference drug SK (79.32% +/-1.629%). In brine shrimp cytotoxic assay, mortality achieved by the extracts showed lethal concentration 50 (LC50) values 274.64 +/- 3.46, 215.60 +/- 4.59, 478.40 +/- 6.98, 233.37 +/- 2.56, and 209.32 +/- 1.98 MUg/ml, respectively, with reference to VS (LC50, 0.05 +/- 0.34). CONCLUSION: In this study, S. indica, R. glauca, and P. acerifolium possessed effective thrombolytic activity. Further studies can be undertaken to identify certain structure of the ingredients in the extracts and to elucidate the precise mechanism of action. SUMMARY: Five Bangladesh medicinal plants, named Piper betle, Pterospermum acerifolium, Saraca indica, Argyreia speciosa, and Rhaphidophora glauca were subjected to comparative antithrombotic and toxicity based analysis. In comparative study, Saraca indica showed highest clot lysis (49.70 +/- 1.69%) activity among the other plant with lowest toxicity (LC50: 478.40 +/- 6.98) Abbreviations Used: h: Hour; min: Minutes; sec: Second; kg: Kilogram; g: Gram; MUg: Microgram; L: Liter; mL: Millilitre; MUL: Micro liter; MUg/mL: Microgram per Milliliter; mg/kg: Milligram per kilogram; %: Percent; degrees C: Degree Celsius; et al.: et alliori (and others); w/w: Weight by Weight; v/v: Volume by Volume; SEM: Standard Error Mean; LC50: lethal concentration at 50. PMID- 27365987 TI - UP1306, a Botanical Composition with Analgesic and Anti-inflammatory Effect. AB - BACKGROUND: Pain, one of the cardinal signs of inflammation, is the most common clinical manifestations of arthritis. Conventional pain relief therapy heavily relies on the use of prescription and over the counter nonsteroidal anti inflammatory drugs as the first line of defense where their long-term usage causes deleterious gastrointestinal and cardiovascular-related side-effects. Hence, there is an equivocal need for evidence-based safer and efficacious alternatives from natural sources to overcome the most prominent and disabling symptoms of arthritis. MATERIALS AND METHODS: Carrageenan-induced rat paw edema and abdominal constriction (writhing's) assays in mouse were used to evaluate the anti-inflammatory and analgesic effects of UP1306, a composition that contains a standardized blend of extracts from the heartwood of Acacia catechu and the root bark of Morus alba administered orally at dose ranges of 100-300 mg/kg. Cyclooxygenase (COX) and lipoxygenase (LOX) inhibition assays were carried out to determine the IC50 of Acacia and Morus extracts. The merit of combining these two extracts was also assessed. RESULTS: Statistically significant improvement in pain resistance and suppression of edema were observed in animals treated with UP1306, when compared to vehicle-treated diseased rats and mice. Results from the high dose of UP1306 (300 mg/kg) were similar to those achieved by ibuprofen treatment at a dose of 200 mg/kg in early hours of treatment. In vitro, UP1306 showed dose-dependent inhibition of the enzymatic activities of COX and LO with IC50 values of 20.9 MUg/mL, 49.2 MUg/mL, and 11.1 MUg/mL in COX-1, COX-2, and 5' LO, respectively. CONCLUSIONS: These data suggest that UP1306, analgesic, and anti-inflammatory agent of botanical origin with dual COX-LO inhibition activity, could potentially be used to alleviate symptom associated to osteoarthritis. SUMMARY: Pain is the most common clinical manifestations of arthritisCarrageenan induced rat paw edema and abdominal constriction (writhing's) assays in mouse are among the widely used models to evaluate the anti-inflammatory and analgesic effects of nutraceuticalsCyclooxygenase and lipoxygenase (LO) inhibition assays were carried out to determine the IC50 of Acacia and Morus extracts.Efficacy of UP1306, a composition containing a blend of two standardized extracts from the heartwood of Acacia catechu and root bark of Morus alba, was evaluated in the above models.UP1306 demonstrated its enhanced significance by improving the major cardinal signs of arthritis in vivo and inflammation markers in vitro.UP1306 could potentially be considered as a dietary supplement product for the management of arthritis. PMID- 27365988 TI - Enhanced Synthesis of Curculigoside by Stress and Amino Acids in Static Culture of Curculigo orchioides Gaertn (Kali Musli). AB - BACKGROUND: Curculigo orchioides Gaertn (Kali musli; Family: Hypoxidaceae) is an endangered medicinal plant used for many medicinal purposes such as impotency, aphrodisiac, tonic, jaundice, and skin ailments. Its hepatoprotective, antioxidant, and anti-cancerous potential have also been evaluated by many scientists. OBJECTIVE: The objective of this study is to enhance the curculigoside content in tissue culture of C. orchioides. MATERIALS AND METHODS: The present study deals with the enhancement of an active compound of C. orchioides by incorporating various concentration of phenylalanine (Phe), tyrosine, (20, 40, 60, and 80 mg/100 ml), chromium (Cr) and nickel (Ni) (1, 2, 3, 4, and 5 ppm) into Zenk media in controlled and aseptic conditions. RESULTS: Plant secondary metabolites are unique sources for pharmaceuticals, food additives, flavors, and industrially important biochemicals. Accumulation of such metabolites often occurs in plants subjected to stresses including various elicitors or signal molecules. A significantly remarkable enhancement in all induced samples was noted. Curculigoside content was maximum in the 6-week-old tissue induced with 3 ppm of Cr (7.63%) followed by 4 weeks tissue of tissue fed with 4 ppm of Ni (5.66%) and 4-week-old tissue fed with tyrosine 7.5 mg/100 ml (2.38%) among all samples used. These results suggest that tyrosine is better enhancer than Phe in the biosynthetic pathway of curculigoside. The presence of curculigoside in all extracts was confirmed by Fourier transform infrared spectroscopy, high-performance thin layer chromatography analysis with standard compound of curculigoside and histology of treated samples. CONCLUSION: This investigation was carried out for the 1(st) time, and it is a significant step in understanding the biochemistry of curculigoside. The developed protocol will be beneficial for marketing in pharmaceutical industries. SUMMARY: Curculigo orchioides Gaertn (Kali musli; Family: Hypoxidaceae) is an endangered medicinal plant used for many medicinal purposes such as impotency, aphrodisiac, tonic, jaundice, and skin ailments.It was observed that dry matter % was maximum in 6 week-old tissue fed with 2.5 mg/100 ml of tyrosine and diminished beyond this concentration among all samples usedThe nickel (Ni) and chromium (Cr) stress has enhanced the curculigoside in considerable amount in nontoxic range, in tissue culture of C. orchioides.Curculigoside content was maximum in 6-week-old tissue induced with 3 ppm of Cr (7.63%; 11-fold enhancement) followed by 4 weeks tissue of tissue fed with 4 ppm of Ni (5.66%) and 4-week-old tissue fed with tyrosine 7.5 mg/100 ml (2.38%) among all samples used. Histological studies confirmed the enhanced production of curculigoside. Abbreviations Used: Phe: Phenylalanine, PAL: Phenylalanine ammonia-lyase, mM: mille Molar, Cr: Chromium, Ni: Nickel, HPTLC: High-performance thin layer chromatography. PMID- 27365989 TI - In vivo Toxicity Studies on Gall Extracts of Terminalia chebula (Gaertn.) Retz. (Combretaceae). AB - The galls of Terminala chebula (Gaertn.) Retz. (Combretaceae) are used for the treatment of various diseases in folk medicine and has been found to posses anti inflammatory, anti-bacterial, anti-helmintic, anti-tyrosinase, and anti-aging activities. Considering the ethano-botanical and diverse pharmacological applications of galls of T. chebula, in this study, we investigate the possible toxic effects of different gall extracts of T. chebula by Brine shrimp (Artemia salina) toxicity assay. The cytotoxicity test of leaf gall extracts (petroleum ether, chloroform, ethanol, and aqueous) of T. chebula was evaluated by Brine shrimp (A. salina) toxicity assay, which is based on the ability to kill laboratory cultured Artemia nauplii (animals eggs) and also total content of polyphenols, flavonoids with other qualitative phytochemical analysis of the extract were determined. It was observed that the petroleum ether extract was virtually nontoxic on the shrimps, and exhibited very low toxicity with LC50 value of 4356.76 MUg/ml. Furthermore, the chloroform extract exhibited very low toxicity, giving LC50 value of 1462.2 MUg/ml. On the other hand, the ethanol extract was very toxic to brine shrimps with LC50 value of 68.64 MUg/ml. The ethanol extract had the highest total phenolic and flavonoid content of 136 +/- 1.5 mg of gallic acid equivalent/g d.w and 113 +/- 1.6 mg of quercetin equivalent/g d.w, respectively. The higher toxicity effect was positively correlated to the high content of total polyphenols/flavonoids in the extract. This significant lethality of different extracts to brine shrimp is an indicative of the presence of potent cytotoxic components which warrants further investigation. SUMMARY: The present study investigates the toxicity effect of different extracts of galls of T. chebulla, which would serve as an index for formulation of drugs for treatment of various diseases. Presumably, these activities could be attributed in part to the polyphenolic features of the extract, as there was a strong correlation of higher toxic effect with that of high total phenolic and flavonoids content in the ethanolic leaf gall extracts of T. chebula. PMID- 27365990 TI - Croton grewioides Baill. (Euphorbiaceae) Shows Antidiarrheal Activity in Mice. AB - Based on chemotaxonomy, we decided to investigate the possible antidiarrheal activity in mice of a crude ethanolic extract obtained from aerial parts of Croton grewioides (CG-EtOH). We tested for any possible toxicity in rat erythrocytes and acute toxicity in mice. Antidiarrheal activity was assessed by determining the effect of CG-EtOH on defecation frequency, liquid stool, intestinal motility and intestinal fluid accumulation. CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females. CG-EtOH produced a significant and equipotent antidiarrheal activity, both in defecation frequency (ED50 = 106.0 +/- 8.1 mg/kg) and liquid stools (ED50 = 105.0 +/- 9.2 mg/kg). However, CG-EtOH (125 mg/kg) decreased intestinal motility by only 22.7% +/- 4.4%. Moreover, extract markedly inhibited the castor oil-induced intestinal contents (ED50 = 34.6 +/- 5.4 mg/kg). We thus conclude that CG-EtOH is not orally lethal and contains active principles with antidiarrheal activity, and this effect seems to involve mostly changes in intestinal secretion. SUMMARY: CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females.CG-EtOH probably contains active metabolites with antidiarrheal activity.CG-EtOH reduced the frequency and number of liquid stools.Metabolites presents in the CG-EtOH act mainly by reducing intestinal fluid and, to a lesser extent, reducing intestinal motility. Abbreviations Used: CG-EtOH: crude ethanolic extract obtained from the aerial parts of C. grewioides; WHO: World Health Organization; ED50: dose of a drug that produces 50% of its maximum effect; Emax: maximum effect. PMID- 27365991 TI - Hepatoprotective and Cytotoxic Activities of Abietic Acid from Isodon wightii (Bentham) H. Hara. AB - Isodon (Lamiaceae) is a known source of bioactive terpenoids. Diterpenoids isolated from Isodon wightii (Bentham) H. Hara showed antibacterial, antiacetylcholinesterase, antioxidant, anticancer, and anticarcinogenic activities, etc., Hepatoprotective activity of ABA against lipopolysaccharide (LPS) induced liver injury in BALB/c mice was studied. Cytotoxic activity of ABA was tested against cervical cancer cells (HeLa) using MTT assay followed by propidium iodide (PI) staining to identify apoptosis. Histopathological analysis revealed that 1.5 ?g/mL LPS induced liver damage was attenuated by ABA in a dose dependent manner. ABA showed cytotoxicity with IC50 value of 176.28 +/- 0.02 ?g/mL and PI staining of treated cells showed apoptosis. This study proves that ABA would be a promising natural compound for herbal drug preparation. SUMMARY: In the present study, abietic acid isolated from I. wightii had potent hepatoprotective effect on LPS induced liver damage in BALB/c mice. Abietic acid also showed cytotoxic activity on HeLa cells followed by apoptosis induction confirmed by PI staining. Abbreviation Used: ABA: Abietic acid; LPS: Lipopolysacharride; PBS: Phosphate buffer saline; PI: Propidium iodide; NMR: Nuclear magnetic resonance; COSY: Correlation spectroscopy; HSQC: Heteronuclear single quantum correlation; HMBC: Heteronuclear multi - bond correlation; MTT: 3 (4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide. PMID- 27365992 TI - Evaluating the Anticancer Potential of Ethanolic Gall Extract of Terminalia chebula (Gaertn.) Retz. (Combretaceae). AB - Plants have been an important source for discovery of anticancer compounds. With the current decline in the number of new molecular entities from the pharmaceutical industry, novel anticancer agents are being sought from traditional medicines; therefore the anticancer efficacy of many plants that are used in traditional medicine is yet to be verified. The objective of the study was to evaluate the cytotoxic potential of ethanolic leaf gall extract of Terminalia chebula are evaluated against buffalo rat liver 3A, MCF-7 (Human mammary gland adenocarcinoma) and A-549 (Human lung cancer) cell lines. The cytotoxic effect of the ethanolic extract was evaluated by MTT assay. The extract was potent and effective in inducing cytotoxic effects in all the cell lines with an IC50 value of 305.18 +/- 1.7 MUg/mL, 643.13 +/- 4.2 MUg/mL, and 208.16 +/- 3.7 MU/mL, respectively. The extract was more effective against A549 cell lines when compared to others. The presences of phenolics, triterpenoids, and flavonoids were identified in the extract. The extract showed total phenolic and flavonoid content of 478 +/- 2.2 mg of gallic acid equivalent/g d.w and 538 +/- 1.4 mg of quercetinequivalent/g d.w, respectively. This higher content of total phenolics and flavonoids found in the ethanolic extract was directly associated to higher cytotoxicity activity. CONCLUSION: The ethanolic leaf gall extract of T. chebula showed effective cytotoxic activities; which might be attributed to the phenolics/flavonoids present in higher concentration. Future work will be interesting to know the chemical composition of the extract and also better understand the mechanism of action of the constituents present in the extract to develop it as drug for therapeutic application. SUMMARY: The present investigation establishes the anticancer activities of T. chebula leaf gall extracts on BRL3A, MCF-7, and A-549 cells. Presumably, these activities could be attributed in part to the phenolics/flavanoids features of the extract that has been demonstrated to act as cytotoxic agents. The experimental evidence obtained in the laboratory model could provide a rationale for the traditional use of plant as a source of easily available effective anticancer agents to the people, particularly in developing countries. PMID- 27365994 TI - Homeopathy in Dentistry: Is There a Role? PMID- 27365993 TI - Inhibition of Group IIA Secretory Phospholipase A2 and its Inflammatory Reactions in Mice by Ethanolic Extract of Andrographis paniculata, a Well-known Medicinal Food. AB - Andrographis paniculata Nees is an important medicinal plant found in the tropical regions of the world, which has been traditionally used in Indian and Chinese medicinal systems. It is also used as medicinal food. A. paniculata is found to exhibit anti-inflammatory activities; however, its inhibitory potential on inflammatory Group IIA phospholipases A2 (PLA2) and its associated inflammatory reactions are not clearly understood. The aim of the present study is to evaluate the inhibitory/neutralizing potential of ethanolic extract of A. paniculata on the isolated inflammatory PLA2 (VRV-PL-VIIIa) from Daboii rusellii pulchella (belonging to Group IIA inflammatory secretory PLA2 [sPLA2]) and its associated edema-induced activities in Swiss albino mice. A. paniculata extract dose dependently inhibited the Group IIA sPLA2 enzymatic activity with an IC50 value of 10.3 +/- 0.5 MUg/ml. Further, the extract dose dependently inhibited the edema formation, when co-injected with enzyme indicating that a strong correlation exists between lipolytic and pro-inflammatory activities of the enzyme. In conclusion, results of this study shows that the ethanolic extract of A. paniculata effectively inhibits Group IIA sPLA2 and its associated inflammatory activities, which substantiate its anti-inflammatory properties. The results of the present study warranted further studies to develop bioactive compound (s) in ethanolic extract of A. paniculata as potent therapeutic agent (s) for inflammatory diseases. SUMMARY: This study emphasis the anti-inflammatory effect of A. paniculata by inhibiting the inflammatory Group IIA sPLA2 and its associated inflammatory activities such as edema. It was found that there is a strong correlation between lipolytic activity and pro-inflammatory activity inhibition. Therefore, the study suggests that the extract processes potent anti inflammatory agents, which could be developed as a potential therapeutic agent against inflammatory and related diseases. PMID- 27365995 TI - Beef from the United States: Is It Safe? PMID- 27365996 TI - Rheumatology in India: a Bird's Eye View on Organization, Epidemiology, Training Programs and Publications. AB - India is home to the world's second largest population. Rheumatology is an emerging specialty in India. We reviewed organization, epidemiology and training facilities for Rheumatology in India. Also, we also looked at publications in the field of rheumatology from India from over the past six years using Scopus and Medline databases. Despite rheumatologic disorders affecting 6%-24% of the population, rheumatology in India is still in its infancy. Till recently, there were as few as two centers in the country training less than five fellows per year. However, acute shortage of specialists and increasing patient numbers led to heightened awareness regarding the need to train rheumatologists. Subsequently, six new centers have now started 3-year training programs in rheumatology. The epidemiology of rheumatic diseases in India is being actively studies under the Community Oriented Programme for Control of Rheumatic Diseases (COPCORD) initiative. The most number of publications on rheumatic diseases from India are on rheumatoid arthritis, lupus and osteoporosis, many of which have been widely cited. Major collaborators worldwide are USA, UK and France, whereas those from Asia are Japan, Saudi Arabia and Singapore. The Indian Rheumatology Association (IRA) is the national organization of rheumatologists. The flagship publication of the IRA, the Indian Journal of Rheumatology, is indexed in Scopus and Embase. To conclude, rheumatology in India is an actively expanding and productive field with significant contributions to world literature. There is a need to train more personnel in the subject in India. PMID- 27365997 TI - Influence of Social Engagement on Mortality in Korea: Analysis of the Korean Longitudinal Study of Aging (2006-2012). AB - The objective of this study was to investigate the impact of social engagement and patterns of change in social engagement over time on mortality in a large population, aged 45 years or older. Data from the Korean Longitudinal Study of Aging from 2006 and 2012 were assessed using longitudinal data analysis. We included 8,234 research subjects at baseline (2006). The primary analysis was based on Cox proportional hazards models to examine our hypothesis. The hazard ratio of all-cause mortality for the lowest level of social engagement was 1.841 times higher (P < 0.001) compared with the highest level of social engagement. Subgroup analysis results by gender showed a similar trend. A six-class linear solution fit the data best, and class 1 (the lowest level of social engagement class, 7.6% of the sample) was significantly related to the highest mortality (HR: 4.780, P < 0.001). Our results provide scientific insight on the effects of the specificity of the level of social engagement and changes in social engagement on all-cause mortality in current practice, which are important for all-cause mortality risk. Therefore, protection from all-cause mortality may depend on avoidance of constant low-levels of social engagement. PMID- 27365998 TI - Quasi-Experiment Study on Effectiveness Evaluation of Health Communication Strategies. AB - This experimental study examined differences in doctor-patient relationships according to the health communication strategies during cases of medical malpractices occurred at primary medical institution. A total of 116 subjects aged in their 20s-50s was sampled. The first medical malpractice scenario chosen was the medical malpractice case most frequently registered at the Korean Medical Association Mutual Aid and the second scenario was associated with materials and devices as the cause of malpractice. Four types of crisis communication strategy messages were utilized, consisting of denial, denial + ingratiation, apology, and apology + ingratiation. Subjects were classified into four research groups by crisis communication strategy to measure levels of trust, control mutuality, commitment, and satisfaction, before and after the occurrence of medical malpractice and application of communication strategies. The findings of this study revealed that the apology strategy, compared with the denial strategy, showed a smaller difference before and after the application of communication strategies in all variables of trust (F = 8.080, F = 5.768), control mutuality (F = 8.824, F = 9.081), commitment (F = 9.815, F = 8.301), and satisfaction (F = 8.723, F = 5.638). Further, a significant interaction effect was shown between variables. The apology strategy, compared with the denial strategy, was effective in the improvement of doctor-patient relationships in both Scenarios I and II. For Scenario I, the apology strategy without ingratiation boosted commitment and satisfaction, but for Scenario II, utilizing the apology strategy with ingratiation boosted the effectiveness of trust and commitment. PMID- 27365999 TI - The Poisoning Information Database Covers a Large Proportion of Real Poisoning Cases in Korea. AB - The poisoning information database (PIDB) provides clinical toxicological information on commonly encountered toxic substances in Korea. The aim of this study was to estimate the coverage rate of the PIDB by comparing the database with the distribution of toxic substances that real poisoning patients presented to 20 emergency departments. Development of the PIDB started in 2007, and the number of toxic substances increased annually from 50 to 470 substances in 2014. We retrospectively reviewed the medical records of patients with toxic exposure who visited 20 emergency departments in Korea from January to December 2013. Identified toxic substances were classified as prescription drug, agricultural chemical, household product, animal or plant, herbal drug, or other. We calculated the coverage rate of the PIDB for both the number of poisoning cases and the kinds of toxic substances. A total of 10,887 cases of intoxication among 8,145 patients was collected. The 470 substances registered in the PIDB covered 89.3% of 8,891 identified cases related to poisoning, while the same substances only covered 45.3% of the 671 kinds of identified toxic substances. According to category, 211 prescription drugs, 58 agricultural chemicals, 28 household products, and 32 animals or plants were not covered by the PIDB. This study suggested that the PIDB covered a large proportion of real poisoning cases in Korea. However, the database should be continuously extended to provide information for even rare toxic substances. PMID- 27366000 TI - Does High Emotional Demand with Low Job Control Relate to Suicidal Ideation among Service and Sales Workers in Korea? AB - We examined the relationship of high emotional demands and low job control to suicidal ideation among service and sales workers in Korea. A total of 1,995 service and sales workers participated in this study. Suicidal ideation and level of emotional demand and job control were assessed by self-reported questionnaire in 4th Korean National Health and Nutrition Examination Survey. Gender-specific odds ratio (OR) and 95% confidence intervals (95% CI) for suicidal ideation were calculated using logistic regression analysis. The results show that workers who suffered from high emotional demands (OR, 2.07; 95% CI, 1.24-3.45 in men, OR, 1.97; 95% CI, 1.42-2.75 in women) or low job control (OR, 1.96; 95% CI, 1.42-2.75 in men, OR, 1.33; 95% CI, 0.91-1.93 in women) were more likely to experience suicidal ideation after controlling for age, household income, and employment characteristics. The interaction model of emotional demands and job control revealed that workers with high emotional demands and high job control (OR, 1.93; 95% CI, 1.08-3.45 in men, OR, 1.60; 95% CI,1.06-2.42 in women) and high emotional demands and low job control (OR; 4.60, 95% CI;1.88-11.29 in men, OR; 2.78, 95% CI;1.64-4.44 in women) had a higher risk for suicidal ideation compared to those with low emotional demands and high job control after controlling for age, household income, employment characteristics, smoking, alcohol drinking and physical activity habit. These results suggest that high emotional demands in both genders and low job control in men might play a crucial role in developing suicidal ideation among sales and service workers in Korea. PMID- 27366001 TI - Peri-Transplant Change in AFP Level: a Useful Predictor of Hepatocellular Carcinoma Recurrence Following Liver Transplantation. AB - Pretransplant alpha-fetoprotein (AFP) is a useful tumor marker predicting recurrence of hepatocellular carcinoma (HCC). Little is known, however, about the relationship between changes in AFP concentration and prognosis. This study investigated the clinical significance of change in peri-transplant AFP level as a predictor of HCC recurrence. Data from 125 HCC patients with elevated pretransplant AFP level who underwent liver transplantation (LT) between February 2000 and December 2010 were retrospectively reviewed. Patients with AFP normalization within 1 month after LT were classified into the rapid normalization group (n = 97), with all other patients classified into the non rapid normalization group (n = 28). Tumor recurrence was observed in 17 of the 97 patients (17.5%) with rapid normalization; of these, 11 patients had high AFP levels and six had normal levels at recurrence. In contrast, tumor recurrence was observed in 24 of the 28 patients (85.7%) without rapid normalization, with all 24 having high AFP levels at recurrence. Multivariate analysis showed that non rapid normalization (harzard ratio [HR], 4.41, P < 0.001), sex (HR, 3.26, P = 0.03), tumor size (HR, 1.15, P = 0.001), and microvascular invasion (HR, 2.65, P = 0.005) were independent risk factors for recurrence. In conclusion, rapid normalization of post-LT AFP level at 1 month is a useful clinical marker for HCC recurrence. Therefore, an adjuvant strategy and/or intensive screening are needed for patients who do not show rapid normalization. PMID- 27366002 TI - High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Children with High-Risk or Recurrent Bone and Soft Tissue Sarcomas. AB - Despite increasing evidence that high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) might improve the survival of patients with high risk or recurrent solid tumors, therapy effectiveness for bone and soft tissue sarcoma treatment remains unclear. This study retrospectively investigated the feasibility and effectiveness of HDCT/auto-SCT for high-risk or recurrent bone and soft tissue sarcoma. A total of 28 patients (18 high-risk and 10 recurrent) underwent single or tandem HDCT/auto-SCT between October 2004 and September 2014. During follow-up of a median 15.3 months, 18 patients exhibited disease progression and 2 died of treatment-related toxicities (1 veno-occlusive disease and 1 sepsis). Overall, 8 patients remained alive and progression-free. The 3 year overall survival (OS) and event-free survival (EFS) rates for all 28 patients were 28.7% and 26.3%, respectively. In the subgroup analysis, OS and EFS rates were higher in patients with complete or partial remission prior to HDCT/auto-SCT than in those with worse responses (OS, 39.1% vs. 0.0%, P = 0.002; EFS, 36.8% vs. 0.0%, P < 0.001). Therefore, careful selection of patients who can benefit from HDCT/auto-SCT and maximal effort to reduce tumor burden prior to treatment will be important to achieve favorable outcomes in patients with high risk or recurrent bone and soft tissue sarcomas. PMID- 27366003 TI - Perception and Attitudes of Korean Obstetricians about Maternal Influenza Vaccination. AB - Pregnant women are prioritized to receive influenza vaccination. However, the maternal influenza vaccination rate has been low in Korea. To identify potential barriers for the vaccination of pregnant women against influenza, a survey using a questionnaire on the perceptions and attitudes about maternal influenza vaccination was applied to Korean obstetricians between May and August of 2014. A total of 473 respondents participated in the survey. Most respondents (94.8%, 442/466) recognized that influenza vaccination was required for pregnant women. In addition, 92.8% (410/442) respondents knew that the incidence of adverse events following influenza vaccination is not different between pregnant and non pregnant women. However, 26.5% (124/468) obstetricians strongly recommended influenza vaccination to pregnant women. The concern about adverse events following influenza vaccination was considered as a major barrier for the promotion of maternal influenza vaccination by healthcare providers. Providing professional information and education about maternal influenza vaccination will enhance the perception of obstetricians about influenza vaccination to pregnant women and will be helpful to improve maternal influenza vaccination coverage in Korea. PMID- 27366004 TI - Effects of Educational Interventions for Chronic Airway Disease on Primary Care. AB - Education has been known to essential for management of chronic airway diseases. However the real benefits remain unclear. We evaluated the effectiveness of an organized educational intervention for chronic airway diseases directed at primary care physicians and patients. The intervention was a 1-month education program of three visits, during which subjects were taught about their disease, an action plan in acute exacerbation and inhaler technique. Asthma control tests (ACT) for asthma and, chronic obstructive pulmonary disease (COPD) assessment tests (CAT) for COPD subjects were compared before and after education as an index of quality of life. Educational effectiveness was also measured associated with improvement of their knowledge for chronic airway disease itself, proper use of inhaler technique, and satisfaction of the subjects and clinicians before and after education. Among the 285 participants, 60.7% (n = 173) were men and the mean age was 62.2 +/- 14.7. ACT for asthma and CAT in COPD patients were significantly improved by 49.7% (n = 79) and 51.2% (n = 65) more than MCID respectively after education (P < 0.05). In all individual items, knowledge about their disease, inhaler use and satisfaction of the patients and clinicians were also improved after education (P < 0.05). This study demonstrates the well organized education program for primary care physicians and patients is a crucial process for management of chronic airway diseases. PMID- 27366005 TI - Management of Suspicious Mucosa-Associated Lymphoid Tissue Lymphoma in Gastric Biopsy Specimens Obtained during Screening Endoscopy. AB - It is often difficult to differentiate gastric mucosa-associated lymphoid tissue (MALT) lymphoma from Helicobacter pylori-associated follicular gastritis, and thus, it becomes unclear how to manage these diseases. This study aimed to explore the management strategy for and the long-term outcomes of suspicious gastric MALT lymphoma detected by forceps biopsy during screening upper endoscopy. Between October 2003 and May 2013, consecutive subjects who were diagnosed with suspicious gastric MALT lymphomas by screening endoscopy in a health checkup program in Korea were retrospectively enrolled. Suspicious MALT lymphoma was defined as a Wotherspoon score of 3 or 4 upon pathological evaluation of the biopsy specimen. Of 105,164 subjects who underwent screening endoscopies, 49 patients with suspicious MALT lymphomas who underwent subsequent endoscopy were enrolled. Eight patients received a subsequent endoscopy without H. pylori eradication (subsequent endoscopy only group), and 41 patients received H. pylori eradication first followed by endoscopy (eradication first group). MALT lymphoma development was significantly lower in the eradication first group (2/41, 4.9%) than in the subsequent endoscopy only group (3/8, 37.5%, P = 0.026). Notably, among 35 patients with successful H. pylori eradication, there was only one MALT lymphoma patient (2.9%) in whom complete remission was achieved, and there was no recurrence during a median 45 months of endoscopic follow-up. H. pylori eradication with subsequent endoscopy would be a practical management option for suspicious MALT lymphoma detected in a forceps biopsy specimen obtained during screening upper endoscopy. PMID- 27366007 TI - Sonographic Growth Charts for Kidney Length in Normal Korean Children: a Prospective Observational Study. AB - Kidney length is the most useful parameter for clinical measurement of kidney size, and is useful to distinguish acute kidney injury from chronic kidney disease. In this prospective observational study of 437 normal children aged between 0 and < 13 years, kidney length was measured using sonography. There were good correlations between kidney length and somatic values, including age, weight, height, and body surface area. The rapid growth of height during the first 2 years of life was intimately associated with a similar increase in kidney length, suggesting that height should be considered an important factor correlating with kidney length. Based on our findings, the following regression equation for the reference values of bilateral kidney length for Korean children was obtained: kidney length of the right kidney (cm) = 0.051 * height (cm) + 2.102; kidney length of the left kidney (cm) = 0.051 * height (cm) + 2.280. This equation may aid in the diagnosis of various kidney disorders. PMID- 27366006 TI - Early Changes in the Serotype Distribution of Invasive Pneumococcal Isolates from Children after the Introduction of Extended-valent Pneumococcal Conjugate Vaccines in Korea, 2011-2013. AB - This study was performed to measure early changes in the serotype distribution of pneumococci isolated from children with invasive disease during the 3-year period following the introduction of 10- and 13-valent pneumococcal conjugate vaccines (PCVs) in Korea. From January 2011 to December 2013 at 25 hospitals located throughout Korea, pneumococci were isolated among children who had invasive pneumococcal disease (IPD). Serotypes were determined using the Quellung reaction, and the change in serotype distribution was analyzed. Seventy-five cases of IPD were included. Eighty percent of patients were aged 3-59 months, and 32% had a comorbidity that increased the risk of pneumococcal infection. The most common serotypes were 19A (32.0%), 10A (8.0%), and 15C (6.7%). The PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, and 6A) accounted for 14.7% of the total isolates and the PCV13 minus PCV7 types (1, 3, 5, 7F and 19A) accounted for 32.0% of the total isolates. Serotype 19A was the only serotype in the PCV13 minus PCV7 group. The proportion of serotype 19A showed decreasing tendency from 37.5% in 2011 to 22.2% in 2013 (P = 0.309), while the proportion of non-PCV13 types showed increasing tendency from 45.8% in 2011 to 72.2% in 2013 (P = 0.108). Shortly after the introduction of extended-valent PCVs in Korea, serotype 19A continued to be the most common serotype causing IPD in children. Subsequently, the proportion of 19A decreased, and non-vaccine serotypes emerged as an important cause of IPD. The impact of extended-valent vaccines must be continuously monitored. PMID- 27366008 TI - The Risk Factors and Pregnancy Outcomes of 48 Cases of Heterotopic Pregnancy from a Single Center. AB - The purpose of this study was to investigate risk factors that are associated with heterotopic pregnancy (HP) following in vitro fertilization (IVF)-embryo transfer (ET) and to demonstrate the outcomes of HP after the surgical treatment of ectopic pregnancies. Forty-eight patients from a single center, who were diagnosed with HP between 1998 and 2012 were included. All of the patients had received infertility treatments, such as Clomid with timed coitus (n = 1, 2.1%), superovulation with intrauterine insemination (n = 7, 14.6%), fresh non-donor IVF ET (n = 33, 68.8%), and frozen-thawed cycles (n = 7, 14.6%). Eighty-four additional patients were randomly selected as controls from the IVF registry database. HP was diagnosed at 7.5 +/- 1.2 weeks (range 5.4-10.3) gestational age. In six cases (12.5%), the diagnosis was made three weeks after the patients underwent treatment for abortion. There were significant differences in the history of ectopic pregnancy (22.5% vs. 3.6%, P = 0.002). There were no significant differences in either group between the rates of first trimester intrauterine fetal loss (15.0% vs. 13.1%) or live birth (80.0% vs. 84.1%) after the surgical treatment for ectopic pregnancy. The risk factors for HP include a history of ectopic pregnancy (OR 7.191 [1.591-32.513], P = 0.010), abortion (OR 3.948 [1.574-9.902], P = 0.003), and ovarian hyperstimulation syndrome (OHSS) (OR 10.773 [2.415-48.060], P = 0.002). In patients undergoing IVF-ET, history of ectopic pregnancy, abortion, and OHSS may be risk factors for HP as compared to the control group of other IVF patients. The surgical treatment of HP does not appear to affect the rates of first trimester fetal loss or live birth. PMID- 27366009 TI - Febrile Urinary Tract Infection after Radical Cystectomy and Ileal Neobladder in Patients with Bladder Cancer. AB - Urinary tract infection (UTI) is one of the most common complications after radical cystectomy and orthotopic neobladder reconstruction. This study investigated the incidence and implicated pathogen of febrile UTI after ileal neobladder reconstruction and identify clinical and urodynamic parameters associated with febrile UTI. From January 2001 to May 2015, 236 patients who underwent radical cystectomy and ileal neobladder were included in this study. Fifty-five episodes of febrile UTI were identified in 46 patients (19.4%). The probability of febrile UTI was 17.6% and 19.8% at 6 months and 24 months after surgery, respectively. While, Escherichia coli was the most common implicated pathogen (22/55, 40.0%), Enterococcus spp. were the most common pathogen during the first month after surgery (18/33, 54.5%). In multivariate logistic regression analysis, ureteral stricture was an independent risk factor associated with febrile UTI (OR 5.93, P = 0.023). However, ureteral stricture accounted for only 6 episodes (10.9%, 6/55) of febrile UTI. Most episodes of febrile UTI occurred within 6 months after surgery. Thus, to identify risk factors associated with febrile UTI in the initial postoperative period, we assessed videourodynamics within 6 months after surgery in 38 patients. On videourodyamic examination, vesicoureteral reflux (VUR) was identified in 16 patients (42.1%). The rate of VUR presence in patients who had febrile UTI was not significantly different from those in patients without febrile UTI (50% vs. 39.3%, P = 0.556). Patients with febrile UTI had significantly larger residual urine volume (212.0 +/- 193.7 vs. 90.5 +/- 148.2, P = 0.048) than those without. E. coli and Enterococcus spp. are common pathogens and ureteral stricture and residual urine are risk factors for UTI after ileal neobladder reconstruction. PMID- 27366010 TI - Psychological Status and Associated Factors among Korean Cancer Survivors: a Cross-Sectional Analysis of the Fourth & Fifth Korea National Health and Nutrition Examination Surveys. AB - It is important to assess psychological distress after a diagnosis for cancer survivors, a population with a high risk for psychological distress. The aim of this study is to assess psychological distress among cancer survivors and to clarify the associated factors. In this cross-sectional analysis, data were obtained from standardized questionnaires administered to 1,163 cancer survivors and 49,243 non-cancer survivors who participated in the Fourth and Fifth Korea National Health and Nutrition Examination Survey (2007-2012). We identified the adjusted rates for psychological distress and assessed factors associated with this kind of distress using multivariate logistic regression. Cancer survivors tended to have a higher adjusted rate of psychological distress than the general population. The current depressive symptom rate for cancer survivors was 16.69%, and the adjusted rate for history of depression in cancer survivors was 15.61%. The adjusted rate for higher level of stress was 25.51% in cancer survivors. Among the cancer survivors, younger subjects, female subjects, and those with limited social support were more prone to psychological distress. In addition, current smokers or risky drinkers, those with chronic diseases, and those with a poor self-perception of their health status were also identified as a high-risk group for psychological distress. As the number of cancer survivors has increased, the importance of assessing psychological distress after a cancer diagnosis should be emphasized among all cancer survivors. Further, psychological supportive care interventions for cancer survivors are needed to improve the survival rate and improve their quality of life. PMID- 27366011 TI - Validation of the Korean-Version of the Clinical Assessment Interview for Negative Symptoms of Schizophrenia (CAINS). AB - The Clinical Assessment Interview for Negative Symptoms (CAINS) was developed to overcome the limitations of existing instruments and reflect the current view of negative symptoms. The aim of the present study was to evaluate the reliability and validity of the Korean version of the Clinical Assessment Interview for Negative Symptoms (K-CAINS). Inpatients (n = 49) and outpatients (n = 70) with schizophrenia were recruited from three institutions. The confirmative factor analysis, test-retest reliability, inter-rater reliability, convergent validity, and discriminant validity were assessed. The study group consisted of 71 males (59.7%) and 48 females (40.3%). Their mean age was 42.15 years (SD = 12.2). The K CAINS was confirmed to be divided into two subscales of 9 items related to "motivation/pleasure" and 4 items related to "expression" in concordance with the original version of the CAINS. The results showed that the K-CAINS had a good inter-rater reliability (ICC = 0.84-0.94), test-retest reliability (r = 0.90, P < 0.001). Convergent validity was proven by demonstrating a significant correlation with the Positive and Negative Syndrome Scale (PANSS) negative subscale, and the Scale for the Assessment of Negative Symptoms (SANS). Discriminant validity was proven by the lack of a significant correlation with the PANSS positive subscale, the Korean version of the Beck depression inventory (BDI), the Korean version of the Calgary depression scale for schizophrenia (K-CDSS), and the Modified Simpson Angus scale (MSAS). The K-CAINS could be a reliable and valid tool to assess the negative symptoms of Korean schizophrenia patients. PMID- 27366012 TI - The Association between Symptoms of Dry Eye Syndrome and Metabolic Outcome in a General Population in Korea. AB - Dry eye syndrome (DES) is recognized as a public health concern. One of the pathophysiologies in the development of DES is inflammation, and metabolic syndrome (MetS), which is highly prevalent in the general population, is a well known chronic and systemic inflammatory condition. Despite the increasing interest regarding a relationship between DES and MetS, information is lacking on the association between DES and MetS and its individual components. We investigated the association between DES symptoms and MetS and its components among adults aged >= 19 years using population-based data from the Korea National Health and Nutrition Examination Survey V. A sample group of 15,294 adults (42.67% men and 57.33% women) completed household interviews in which they provided blood (for high-density lipoprotein cholesterol, triglyceride, and glucose) and anthropometric measurements (including waist circumference, weight, and height) to define MetS. We also collected information regarding sociodemographic and behavioral risk factors. The survey results showed that 11.50% of men and 22.35% of women experienced DES and 5.30% of patients had both DES and diagnosis of MetS, including 204 men and 606 women. Thus, no significant difference was observed between DES and the diagnosis of MetS according to sex (P = 0.4008 in men; P = 0.0804 in women); however, a significant association was observed between DES and hypertriglyceridemia in women (OR, 1.13; 95% CI, 1.01 1.29). Therefore, hypertriglyceridemia might be an important factor in the association between DES and MetS. Further longitudinal research is needed to evaluate this relationship. PMID- 27366013 TI - Effect of Hydroxychloroquine Treatment on Dry Eyes in Subjects with Primary Sjogren's Syndrome: a Double-Blind Randomized Control Study. AB - The effect of hydroxychloroquine (HCQ) on dry eye has not been fully determined. This study aimed to compare the 12-week efficacy of HCQ medication with that of a placebo in the management of dry eye in primary Sjogren's syndrome (pSS). A double-blind, randomized control study was conducted in 39 pSS subjects from May 2011 through August 2013. pSS was diagnosed based on the classification criteria of the American-European Consensus Group. Subjects received 300 mg of HCQ or placebo once daily for 12 weeks and were evaluated at baseline, 6, and 12 weeks, with a re-visit at 16 weeks after drug discontinuance. The fluorescein staining score, Schirmer test score, tear film break-up time (TBUT), and ocular surface disease index (OSDI) were measured, and tears and blood were collected for ESR, IL-6, IL-17, B-cell activating factor (BAFF), and Th17 cell analysis. Color testing was performed and the fundus was examined to monitor HCQ complications. Twenty-six subjects completed the follow-up. The fluorescein staining score and Schirmer test score did not differ significantly. The OSDI improved with medication in the HCQ group but was not significantly different between the groups. TBUT, serum IL-6, ESR, serum and tear BAFF, and the proportion of Th17 cells did not change in either group. HCQ at 300 mg daily for 12 weeks has no apparent clinical benefit for dry eye and systemic inflammation in pSS (ClinicalTrials.gov. NCT01601028). PMID- 27366014 TI - An Analysis of the Filaggrin Gene Polymorphism in Korean Atopic Dermatitis Patients. AB - Research of the FLG mutation in various ethnic groups revealed non-overlapping mutation patterns. In addition, Japanese and Chinese atopic patients showed somewhat different mutations. These ethnic differences make the research on Korean patients mandatory; however, no systematic research on Korean atopic dermatitis (AD) patients has been performed. This study aims to investigate the genetic polymorphism of FLG in Korean atopic dermatitis patients. The study was made up of three groups including 9 Ichthyosis vulgaris (IV) patients, 50 AD patients and 55 normal controls: the ichthyosis group was incorporated due to the reported association between the FLG mutation and IV. In comparison to other sequencing methods, the overlapping long-range PCR was used. We revealed the genetic polymorphism of filaggrin in Koreans, and at the same time, we discovered nonsense mutations in p.Y1767X and p.K4022X in Korean AD patients. By using FLG sequencing techniques confirmed in this study, new mutations or genetic polymorphisms with ethnic characteristics would be detected and further larger studies of repeat number polymorphisms could be performed. PMID- 27366015 TI - Progression of Hip Displacement during Radiographic Surveillance in Patients with Cerebral Palsy. AB - Progression of hip displacement is common in patients with cerebral palsy (CP). We aimed to investigate the rate of progression of hip displacement in patients with CP by assessing changes in radiographic indices according to Gross Motor Function Classification System (GMFCS) level during hip surveillance. We analyzed the medical records of patients with CP aged < 20 years who underwent at least 6 months interval of serial hip radiographs before any surgical hip intervention, including reconstructive surgery. After panel consensus and reliability testing, radiographic measurements of migration percentage (MP), neck-shaft angle (NSA), acetabular index (AI), and pelvic obliquity (PO) were obtained during hip surveillance. For each GMFCS level, annual changes in radiographic indices were analyzed and adjusted for affecting factors, such as sex, laterality, and type of CP. A total of 197 patients were included in this study, and 1,097 radiographs were evaluated. GMFCS classifications were as follows: 100 patients were level I III, 48 were level IV, and 49 were level V. MP increased significantly over the duration of hip surveillance in patients with GMFCS levels I-III, IV, and V by 0.3%/year (P < 0.001), 1.9%/year (P < 0.001), and 6.2%/year (P < 0.001), respectively. In patients with GMFCS level IV, NSA increased significantly by 3.4 degrees /year (P < 0.001). Our results suggest that periodic monitoring and radiographic hip surveillance is warranted for patients with CP, especially those with GMFCS level IV or V. Furthermore, physicians can predict and inform parents or caregivers regarding the progression of hip displacement in patients with CP. PMID- 27366016 TI - The Anion Gap is a Predictive Clinical Marker for Death in Patients with Acute Pesticide Intoxication. AB - Pesticide formulation includes solvents (methanol and xylene) and antifreeze (ethylene glycol) whose metabolites are anions such as formic acid, hippuric acid, and oxalate. However, the effect of the anion gap on clinical outcome in acute pesticide intoxication requires clarification. In this prospective study, we compared the anion gap and other parameters between surviving versus deceased patients with acute pesticide intoxication. The following parameters were assessed in 1,058 patients with acute pesticide intoxication: blood chemistry (blood urea nitrogen, creatinine, glucose, lactic acid, liver enzymes, albumin, globulin, and urate), urinalysis (ketone bodies), arterial blood gas analysis, electrolytes (Na(+), K(+), Cl(-) HCO3 (-), Ca(++)), pesticide field of use, class, and ingestion amount, clinical outcome (death rate, length of hospital stay, length of intensive care unit stay, and seriousness of toxic symptoms), and the calculated anion gap. Among the 481 patients with a high anion gap, 52.2% had a blood pH in the physiologic range, 35.8% had metabolic acidosis, and 12.1% had acidemia. Age, anion gap, pesticide field of use, pesticide class, seriousness of symptoms (all P < 0.001), and time lag after ingestion (P = 0.048) were significant risk factors for death in univariate analyses. Among these, age, anion gap, and pesticide class were significant risk factors for death in a multiple logistic regression analysis (P < 0.001). In conclusions, high anion gap is a significant risk factor for death, regardless of the accompanying acid-base balance status in patients with acute pesticide intoxication. PMID- 27366017 TI - Pralatrexate in Combination with Bortezomib for Relapsed or Refractory Peripheral T Cell Lymphoma in 5 Elderly Patients. AB - Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with poor prognosis. Elderly (age >= 65years) patients generally have impaired bone marrow function, altered drug metabolism, comorbidities, and poor functional status. Thus, treatment of elderly patients with relapsed or refractory PTCL remains a challenge for clinicians. A recent study disclosed that pralatrexate has a synergistic effect in combination with bortezomib. Weekly pralatrexate and bortezomib were administered intravenously for 3 weeks in a 4 week cycle. Of 5 patients, one achieved complete response after 4 cycles which has lasted 12 months until now. Another patient attained partial response after 2 cycles. Only 1 patient experienced grade 3 thrombocytopenia and neutropenia. Two patients suffered from grade 3 mucositis. Combination therapy with pralatrexate and bortezomib may be used as a salvage therapy for relapsed or refractory PTCL in the elderly with a favorable safety profile. PMID- 27366018 TI - A Case of Mushroom Poisoning with Russula subnigricans: Development of Rhabdomyolysis, Acute Kidney Injury, Cardiogenic Shock, and Death. AB - Mushroom exposures are increasing worldwide. The incidence and fatality of mushroom poisoning are reported to be increasing. Several new syndromes in mushroom poisoning have been described. Rhabdomyolytic mushroom poisoning is one of new syndromes. Russula subnigricans mushroom can cause delayed-onset rhabdomyolysis with acute kidney injury in the severely poisoned patient. There are few reports on the toxicity of R. subnigricans. This report represents the first record of R. subnigricans poisoning with rhabdomyolysis in Korea, describing a 51-year-old man who suffered from rhabdomyolysis, acute kidney injury, severe hypocalcemia, respiratory failure, ventricular tachycardia, cardiogenic shock, and death. Mushroom poisoning should be considered in the evaluation of rhabdomyolysis of unknown cause. Furthermore, R. subnigricans should be considered in the mushroom poisoning with rhabdomyolysis. PMID- 27366019 TI - Two Siblings with Adolescent/Adult Onset Niemann-Pick Disease Type C in Korea. AB - Niemann-Pick disease, type C (NP-C), is caused by NPC1 or NPC2 gene mutations. Progressive neurological, psychiatric, and visceral symptoms are characteristic. Here, we present cases of a brother (Case 1) and sister (Case 2) in their mid-20s with gait disturbance and psychosis. For the Case 1, neurological examination revealed dystonia, ataxia, vertical supranuclear-gaze palsy (VSGP), and global cognitive impairment. Case 2 showed milder, but similar symptoms, with cortical atrophy. Abdominal computed tomography showed hepatosplenomegaly in both cases. NPC1 gene sequencing revealed compound heterozygote for exon 9 (c.1552C>T [R518W]) and exon 18 (c.2780C>T [A927V]). Filipin-staining tests were also positive. When a young patient with ataxia or dystonia shows VSGP, NP-C should be considered. PMID- 27366020 TI - First Imported Case of Zika Virus Infection into Korea. AB - Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifestations. Zika virus was isolated from his semen, and reverse-transcriptase PCR was positive for the virus in the blood, urine, and saliva on the 7th day of the illness but was negative on the 21st day. He recovered spontaneously without any neurological complications. He is the first case of Zika virus infection in Korea imported from Brazil. PMID- 27366022 TI - Simultaneous quantitative analysis of main components in linderae reflexae radix with one single marker. AB - Establish a quantitative analysis of multi-components by the single marker (QAMS) method for quality evaluation and validate its feasibilities by the simultaneous quantitative assay of four main components in Linderae Reflexae Radix. Four main components of pinostrobin, pinosylvin, pinocembrin, and 3,5-dihydroxy-2-(1-p mentheneyl)-trans-stilbene were selected as analytes to evaluate the quality by RP-HPLC coupled with a UV-detector. The method was evaluated by a comparison of the quantitative results between the external standard method and QAMS with a different HPLC system. The results showed that no significant differences were found in the quantitative results of the four contents of Linderae Reflexae Radix determined by the external standard method and QAMS (RSD <3%). The contents of four analytes (pinosylvin, pinocembrin, pinostrobin, and Reflexanbene I) in Linderae Reflexae Radix were determined by the single marker of pinosylvin. This fingerprint was the spectra determined by Shimadzu LC-20AT and Waters e2695 HPLC that were equipped with three different columns. PMID- 27366023 TI - Celiac-associated pancreatic disease. PMID- 27366021 TI - Extragenital Infections Caused by Chlamydia trachomatis and Neisseria gonorrhoeae: A Review of the Literature. AB - In the United States, sexually transmitted diseases due to Chlamydia trachomatis and Neisseria gonorrhoeae continue to be a major public health burden. Screening of extragenital sites including the oropharynx and rectum is an emerging practice based on recent studies highlighting the prevalence of infection at these sites. We reviewed studies reporting the prevalence of extragenital infections in women, men who have sex with men (MSM), and men who have sex only with women (MSW), including distribution by anatomical site. Among women, prevalence was found to be 0.6-35.8% for rectal gonorrhea (median reported prevalence 1.9%), 0-29.6% for pharyngeal gonorrhea (median 2.1%), 2.0-77.3% for rectal chlamydia (median 8.7%), and 0.2-3.2% for pharyngeal chlamydia (median 1.7%). Among MSM, prevalence was found to be 0.2-24.0% for rectal gonorrhea (median 5.9%), 0.5-16.5% for pharyngeal gonorrhea (median 4.6%), 2.1-23.0% for rectal chlamydia (median 8.9%), and 0-3.6% for pharyngeal chlamydia (median 1.7%). Among MSW, the prevalence was found to be 0-5.7% for rectal gonorrhea (median 3.4%), 0.4-15.5% for pharyngeal gonorrhea (median 2.2%), 0-11.8% for rectal chlamydia (median 7.7%), and 0-22.0% for pharyngeal chlamydia (median 1.6%). Extragenital infections are often asymptomatic and found in the absence of reported risk behaviors, such as receptive anal and oral intercourse. We discuss current clinical recommendations and future directions for research. PMID- 27366024 TI - Advances in the development of new biologics in inflammatory bowel disease. AB - Biologics have revolutionized the therapeutic approach in inflammatory bowel disease (IBD). Anti-tumor necrosis factor (anti-TNF) agents infliximab and adalimumab currently constitute the major biological therapy in IBD. Additional anti-TNFs such as golimumab and other new biologics are currently being developed for both anti-TNF-naive and -resistant patients. These include anti-integrins (vedolizumab and etrolizumab), a JAK inhibitor (tofacitinib) and an anti-anti interleukin (IL)-23 and IL-12 antibody (ustekinumab), among additional drugs in development. The following review discusses the indications, efficacy and safety issues for these novel medications. PMID- 27366025 TI - Endoscopy after bariatric surgery. AB - Obesity is a global epidemic with significant morbidity and mortality. Weight loss results in reduction of health risks and improvement in quality of life, thus representing a goal of paramount importance. Bariatric surgery is the most efficacious choice compared to conservative alternatives including diet, exercise, drugs and behavioral modification to treat obese patients. Following bariatric operations, patients may present with upper gastrointestinal tract complaints that warrant endoscopic evaluation and the various bariatric surgery types are often linked to complications. A subset of these complications necessitates endoscopic interventions for accurate diagnosis and effective, minimal invasive treatment. This review aims to highlight the role of upper gastrointestinal endoscopy in patients who have undergone bariatric surgery to evaluate and potentially treat surgery-related complications and upper gastrointestinal symptoms. PMID- 27366026 TI - Neutrophil anti-neutrophil cytoplasmic autoantibody proteins: bactericidal increasing protein, lactoferrin, cathepsin, and elastase as serological markers of inflammatory bowel and other diseases. AB - Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract comprising Crohn's disease and ulcerative colitis. Although the pathogenesis of the disease is not clearly defined yet, environmental, genetic and other factors contribute to the onset of the disease. Apart from the clinical and histopathological findings, several serological biomarkers are also employed to detect IBD. One of the most thoroughly studied biomarker is anti-neutrophil cytoplasmic autoantibody (ANCA). We herein provide an overview of the current knowledge on the use of ANCA and certain ANCA proteins, such as bactericidal increasing protein, lactoferrin, cathepsin G and elastase, as serological markers for IBD and other diseases. PMID- 27366027 TI - Favorable results from the use of herbal and plant products in inflammatory bowel disease: evidence from experimental animal studies. AB - The use of herbal therapy for inflammatory bowel disease is increasing worldwide. The aim of this study was to review the available literature on the efficacy of herbal therapy in experimental colitis. All relevant studies published in Medline and Embase up to June 2015 have been reviewed. The results of bowel histology and serum parameters have been recorded. A satisfactory number of published experimental studies, and a quite large one of both herbal and plant products tested in different studies have been reported. The results showed that in the majority of the studies, herbal therapy reduced the inflammatory activity of experimental colitis and diminished the levels of many inflammatory indices, including serum cytokines and indices of oxidative stress. The most promising plant and herbal products were tormentil extracts, wormwoodherb, Aloe vera, germinated barley foodstuff, curcumin, Boswellia serrata, Panax notoginseng, Ixeris dentata, green tea, Cordia dichotoma, Plantago lanceolata, Iridoidglycosides, and mastic gum. Herbal therapies exert their therapeutic benefit via various mechanisms, including immune regulation, anti-oxidant activity, inhibition of leukotriene B4 and nuclear factor-kappaB, and antiplatelet activity. Large, double-blind clinical studies assessing these natural substances should be urgently conducted. PMID- 27366028 TI - Safety and efficacy of daclatasvir in the management of patients with chronic hepatitis C. AB - Daclatasvir (DaklinzaTM), a new oral direct-acting antiviral, is an inhibitor of hepatitis C virus NS5A protein and has recently been approved in the United States, Europe and Japan in chronic hepatitis C. It shows potent pangenotypic activity and moderately high genetic barrier to resistance improving the sustained virological response (SVR) rates. In COMMAND phase 2 trials, daclatasvir demonstrated high SVR rates in HCV genotype 1-4 chronically infected patients treated with peginterferon-a (pegIFNalpha) plus ribavirin (RBV). Furthermore, it produced even higher response rates in all-oral combination with sofosbuvir, an interferon-free regimen, with or without ribavirin, in patients with advanced liver disease, HCV/HIV coinfection, liver transplantation in ALLY studies and other real-world studies. This narrative review provides information on the pharmacological properties, role, efficacy and safety of daclatasvir containing regimens in chronic hepatitis C patients. Daclatasvir administered once-daily in combination with sofosbuvir is an effective 12-week treatment in adult patients with chronic hepatitis C and is generally safe and well tolerated. PMID- 27366029 TI - Vitamin D deficiency in patients with liver cirrhosis. AB - There is ongoing evidence that vitamin D is related to the pathophysiology of cirrhosis. Although the incidence of vitamin D deficiency in chronic liver diseases and cirrhosis is strongly documented, its pathogenic association with advanced liver fibrosis remains controversial. There is evidence of a significant relation of 25(OH)D levels with the degree of liver dysfunction, considering that an inverse correlation of 25(OH)D levels with both Child-Pugh score and Model for End-Stage Liver Disease has been reported. In addition, vitamin D deficiency has been shown to increase the risk for overall mortality and infections in patients with cirrhosis. Vitamin D deficiency has been also associated with advanced stages of hepatocellular carcinoma and poor prognosis. Finally, there are studies suggesting that patients with chronic hepatitis C and normal vitamin D levels have higher virological response to treatment. However, there are not enough studies conducted in cirrhotic-only populations. The association between vitamin D and cirrhosis demonstrates a great potential for clinical application. The relation between vitamin D deficiency and the degree of liver function, degree of fibrosis and infectious complications could support its use as a prognostic index and a diagnostic tool. PMID- 27366030 TI - Endoscopic ultrasound-guided fine-needle aspiration in the diagnosis of adrenal lesions. AB - The use of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) appears to be a safe and feasible means of confirming or excluding malignancy in the adrenal glands. EUS-FNA with biopsy of suspicious masses in either adrenal gland allows for assessment of these lesions while keeping complications relatively rare. The main advantages of EUS-FNA are that it can be done as an outpatient procedure, with good results, minimal morbidity, and a short hospital stay. Nevertheless, EUS-FNA of adrenal masses should be indicated only in selected cases, in which there is potential to either decrease unnecessary treatment or guide therapy in cancer patients by aiding in either staging of malignancy or treatment of recurrence.v. PMID- 27366031 TI - Pre-endoscopic erythromycin administration in upper gastrointestinal bleeding: an updated meta-analysis and systematic review. AB - BACKGROUND: In patients suffering from upper gastrointestinal bleeding (UGIB), adequate visualization is essential during endoscopy. Prior to endoscopy, erythromycin administration has been shown to enhance visualization in these patients; however, guidelines have not fully adopted this practice. Thus, we performed a comprehensive, up-to-date meta-analysis on the issue of erythromycin administration in this patient population. METHODS: After searching multiple databases (November 2015), randomized controlled trials on adult subjects comparing administration of erythromycin before endoscopy in UGIB patients to no erythromycin or placebo were included. Pooled estimates of adequacy of gastric mucosa visualized, need for second endoscopy, duration of procedure, length of hospital stay, units of blood transfused, and need for emergent surgery using odds ratio (OR) or mean difference (MD) were calculated. Heterogeneity and publication bias were assessed. RESULTS: Eight studies (n=598) were found to meet the inclusion criteria. Erythromycin administration showed statistically significant improvement in adequate gastric mucosa visualization (OR 4.14; 95% CI: 2.01-8.53, P<0.01) while reduced the need for a second-look endoscopy (OR 0.51; 95% CI: 0.34-0.77, P<0.01) and length of hospital stay (MD -1.75; 95% CI: 2.43 to -1.06, P<0.01). Duration of procedure (P=0.2), units of blood transfused (P=0.08), and need for emergent surgery (P=0.88) showed no significant differences. CONCLUSION: Pre-endoscopic erythromycin administration in UGIB patients significantly improves gastric mucosa visualization while reducing length of hospital stay and the need for second-look endoscopy. PMID- 27366032 TI - Importance of colonoscopy in patients undergoing endoscopic resection for superficial esophageal squamous cell carcinoma. AB - BACKGROUND: The aim of the study was to clarify the frequency of colorectal neoplasm (CRN) complicating superficial esophageal squamous cell carcinoma (ESCC) and the need for colonoscopy. METHODS: We retrospectively reviewed 101 patients who had undergone initial endoscopic resection (ER) for superficial ESCC. Control group participants were age- and sex-matched asymptomatic subjects screened at our hospital over the same period of time. Advanced adenoma was defined as an adenoma >=10 mm, with villous features, or high-grade dysplasia. Advanced CRN referred to advanced adenoma or cancer. We measured the incidence of advanced CRN in superficial ESCC and controls, and we compared the characteristics of superficial ESCC patients with and without advanced CRN. RESULTS: In the superficial ESCC group, advanced CRNs were found in 17 patients (16.8%). A history of smoking alone was found to be a significant risk factor of advanced CRN [odds ratio 6.02 (95% CI 1.30-27.8), P=0.005]. CONCLUSION: The frequency of synchronous advanced CRN is high in superficial ESCC patients subjected to ER. Colonoscopy should be highly considered for most patients who undergo ER for superficial ESCC with a history of smoking, and is recommended even in superficial ESCC patients. PMID- 27366033 TI - Gastric adenocarcinoma: clinicopathologic differences among Hispanics and non Hispanic whites. A single Institution's experience over 14 years. AB - BACKGROUND: Gastriccancer is a leading cause of cancer death worldwide and has significant ethnic and socioeconomic differences in distribution. The aim of this study was to compare clinicopathologic characteristics and survival between Hispanics (H) and non-Hispanic whites (NHW) with gastric cancer. METHODS: We reviewed the records of all patients diagnosed with gastric cancer between 1999 and 2013 at our institution. A total of 638 patients were studied. Demographics, tumor characteristics and survival rate were analyzed. Kaplan-Meier was used for survival analysis. RESULTS: There were 101 H and 537 NHW. The median age at diagnosis was 63 years in H and 69 years in NHW. At diagnosis, 48 (48%) of H patients had stage IV disease compared with 195 (36%) of NHW (P<0.03). H were more likely to have distal cancers and poorly differentiated tumors compared to NHW (44% vs. 15%, P<0.0001; 70% vs. 50%, P<0.0002, respectively). There was a significant difference in median overall survival between the two groups, being 51 months for H (95% CI: 34.6-66.9) and 99 months for NHW (95% CI: 77.3-120.7) P<0.0001. In multivariate analysis, age (OR: 1.02, 95% CI: 1.02-1.03, P<0.0001), poor differentiation (OR: 1.21, 95% CI: 1.02-1.43, P<0.02), ethnicity (OR: 1.69, 95% CI: 1.07-2.55, P<0.02), and stage (OR: 1.95, 95% CI: 1.77-2.15, P<0.0001) were independent predictors of survival. CONCLUSIONS: H patients were diagnosed with gastric cancer at a younger age, to present with advanced disease at diagnosis, and had shorter overall survival compared to NHW. PMID- 27366035 TI - Place of birth, cancer beliefs and being current with colon cancer screening among US adults. AB - BACKGROUND: Historically, studies suggested that immigrants acquire the risk of colorectal cancer (CRC) as US-born persons within the same generation. CRC risk of immigrants is largely unknown in this era of cancer screening and widespread immigration. We investigated the association of place of birth and cancer beliefs with uptake of CRC screening. METHODS: The 2007 Health Information National Trends Survey was used and 4,299 respondents (weighted population size=81,896,392) who were 50 years and older (3,960 US-born and 339 foreign-born) were identified. We defined being current with CRC screening guidelines as the use of fecal occult blood test within 1 year, sigmoidoscopy within 5 years, or colonoscopy within 10 years. We compared being up-to-date with CRC screening among foreign-born versus US-born respondents. Logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Overall, 2,594 (63.3%) US-born and 208 (52.8%) foreign-born respondents were current with CRC screening. Foreign-born respondents were less current in unadjusted model (OR 0.65; 95% CI: 0.50-0.85) but became non-statistically significant after adjustment (OR 0.79; 95% CI: 0.51-1.24). Respondents who believed that screening finds cancer when it is easy to treat (OR 2.85; 95% CI: 1.44-3.61), those who believed that cancer can be cured when detected early (OR 1.56; 95% CI: 1.20-2.00), and those who worry about getting cancer (OR 1.34; 95% CI: 1.10-1.61) were likely to be current with CRC screening. However, respondents with fatalistic beliefs were borderline less likely to be current (OR 0.82; 95% CI: 0.65-1.04). CONCLUSION: There is a need to improve education on CRC screening, particularly among foreign-born adults. PMID- 27366034 TI - Impact of glycemic control on colonoscopy outcomes: bowel preparation and polyp detection. AB - BACKGROUND: The negative effect of diabetes mellitus (DM) on the colonoscopy preparation has been previously established. Metabolic syndrome has been shown to increase risk for malignancy and possibly for premalignant lesions. This study aimed to investigate the impact of DM control on colonoscopy outcomes including bowel preparation and adenoma detection rate (ADR). METHODS: We included patients with DM who underwent colonoscopy in our hospital and had a documented glycated hemoglobin (HbA1C) within 3 months. Patients were categorized into three groups based on their HbA1C level. The clinical and endoscopic data were collected and analyzed. RESULTS: Our cohort included 352 DM patients. The mean age was 63.5 years. When patients were analyzed based on HBA1C, bowel preparation was poor in 46.7% of patients with good glycemic control, 52.1% of patients with fair control and 50% of patients with poor control. ADR was 24.3% in patients with good glycemic control, 20.2% in patients with fair glycemic control and 27.1% in patients with poor glycemic control. There was no statistically significant difference in the quality of preparation or adenoma detection amongst the groups. CONCLUSION: The degree of glycemic control did not impact the quality of bowel preparation or ADR. PMID- 27366036 TI - Systematic review and meta-analysis of third-line salvage therapy with infliximab or cyclosporine in severe ulcerative colitis. AB - BACKGROUND: In patients with ulcerative colitis who fail corticosteroids and are treated with rescue therapy (e.g. infliximab or cyclosporine) but fail to respond, salvage therapy with infliximab or cyclosporine can be considered. We sought to assess the efficacy and safety of this third-line salvage therapy. METHODS: We performed a meta-analysis of trials published in PubMed up to January 2015 relating to the use of third-line salvage therapy following failure of intravenous corticosteroids and infliximab or cyclosporine. Pooled outcome rates for each salvage strategy and pooled odds ratio comparing the two strategies were calculated using the random effects model. Heterogeneity was assessed by the Q and I(2) statistics. RESULTS: The search strategy yielded 40 articles of which 4 were eligible for inclusion. Four articles assessed patients who were treated with infliximab after failure of cyclosporine and 2 articles assessed the use of cyclosporine after failure of infliximab. There were 138 patients using infliximab as a third-line salvage therapy and 30 patients using cyclosporine. When comparing these two strategies, there was no significant difference in clinical response (RR 1.03, 95%CI 0.7-1.46 P=0.87), clinical remission (RR 0.69, 95%CI 0.30-1.57 P=0.37), or colectomy at 12 months (RR 1.14, 95%CI 0.79-1.67 P=0.48). Similarly, there was no significant difference in total (RR 1.91, 95% CI0.38-9.64 p=0.43) or serious adverse events (RR 1.18, 95%CI 0.34-4.07 P=0.80). CONCLUSION: While third-line salvage therapy may be efficacious in achieving short-term clinical response/remission, there remains a significant risk of colectomy and adverse events. PMID- 27366037 TI - Hepatitis B viral replication influences the expression of natural killer cell ligands. AB - BACKGROUND: Hepatitis B virus (HBV) is accounting for over one million deaths annually due to immune-mediated chronic liver damage. Natural killer (NK) cells are abundant in the liver and contribute in HBV persistence. NK cytotoxic effects are controlled by signals from activating and inhibitory receptors. HBV may circumvent host antiviral immunity via the regulation of NK receptors and their ligands. We investigated the effect of viral replication and HBeAg mutations on NK mediators expression in the livers of chronic HBV (CHB) patients and in cell cultures. METHODS: HBV monomers bearing hotspot mutations in the basal core promoter and precore region were transfected into HepG2 cells using a plasmid free assay. Serum viremia and liver HBV RNA were measured in 19 CHB patients. The expression of HBV RNA and of NKG2D ligands, B7H6, DNAX accessory molecule-1, lectin-like transcript 1 (LLT1), LFA-1 and TRAIL was measured in the livers of CHB patients and transfected cells. RESULTS: In general, high HBV replication in CHB patients and cell lines upregulated the mRNA of all NK cell ligands and particularly the inhibitory NK cell ligand, LLT1. The exception was the NKG2D ligand, MICA, that was significantly decreased in patients with high serum viremia and intrahepatic HBV RNA levels. CONCLUSIONS: HBV replication has differential effects on NK cell ligands suggesting a potential escape mechanisms through up-regulation of LLT1 and down-regulation of MICA. A general trend towards upregulating NK cell ligands can be counteracted by decreasing MICA and hence weakening NK surveillance. PMID- 27366038 TI - Real-time elastography as a noninvasive assessment of liver fibrosis in chronic hepatitis C Egyptian patients: a prospective study. AB - BACKGROUND: Hepatitis C virus is a worldwide problem. Noninvasive methods for liver fibrosis assessment as ultrasound-based approaches have emerged to replace liver biopsy. The aim of this study was to evaluate the diagnostic accuracy of real-time elastography (RTE) in the assessment of liver fibrosis in patients with chronic hepatitis C (CHC), compared with transient elastography and liver biopsy. METHODS: RTE, FibroScan and liver biopsy were performed in 50 CHC patients. In addition, aspartate aminotransferase to platelet ratio index (APRI) and routine laboratory values were included in the analysis. RESULTS: RTE was able to diagnose significant hepatic fibrosis (F >=2) according to METAVIR scoring system at cut-off value of 2.49 with sensitivity 100%, specificity 66%, and area under the receiver-operating characteristics (AUROC) 0.8. FibroScan was able to predict significant fibrosis at cut-off value 7.5 KPa with sensitivity 88%, specificity 100%, and AUROC 0.94.APRI was able to predict significant hepatic fibrosis (F >=2) with sensitivity 54%, specificity 80%, and AUROC 0.69. There was a significant positive correlation between the FibroScan score and RTE score (r=0.6, P=0.001). CONCLUSIONS: Although FibroScan is superior in determining significant hepatic fibrosis, our data suggest that RTE may be a useful and promising noninvasive method for liver fibrosis assessment in CHC patients especially in cases with technical limitations for FibroScan. PMID- 27366039 TI - Is pancreatic exocrine insufficiency in celiac disease related to structural alterations in pancreatic parenchyma? AB - BACKGROUND: Although exocrine pancreatic insufficiency (EPI) has been reported in a number of patients with celiac disease (CD), it is not clear if this is primarily a functional or a structural defect. We studied pancreatic structural abnormalities by endoscopic ultrasound (EUS) in adult CD patients with EPI. METHODS: Pancreatic exocrine function was prospectively assessed in 36 recently diagnosed CD patients (mean age: 29.8 years) by measuring fecal elastase. Pancreatic structural changes were assessed in CD patients with EPI by EUS and elastography. Exocrine functions were reassessed after 3 months of gluten-free diet. RESULTS: Of the 36 CD patients included, 30 (83%) had anemia, 21 (58%) diarrhea, and 7 (19%) hypothyroidism. Ten (28%) patients had EPI with mean elastase levels of 141.6 MUg/g of stool, of whom only one had a history of recurrent acute pancreatitis while the rest 9 patients had no history of acute or chronic pancreatitis. Of these 10 patients, 8 (80%) had diarrhea, 8 (80%) anemia, and 2 (20%) hypothyroidism. EUS was done in 8 patients which showed: normal pancreas in 5 (50%), hyperechoic strands in 3 (30%), and hyperechoic foci without shadowing in 2 (20%) patients. None had lobularity or parenchymal calcification. All patients except the patient with recurrent pancreatitis had normal strain ratio. Follow-up fecal elastase was within normal range in 6 of 7 (86%) patients. CONCLUSION: EPI, assessed by fecal elastase levels in adult CD patients, possibly does not relate to structural alterations in the pancreatic parenchyma and may be reversible by following a gluten-free diet. PMID- 27366040 TI - Diagnostic yield of secretin-enhanced magnetic resonance cholangiopancreatography in the investigation of patients with acalculous biliary pain. AB - BACKGROUND: Secretin-enhanced magnetic resonance cholangiopancreatography (S MRCP) facilitates better visualization of the pancreaticobiliary ductal system but its role in patients with acalculous biliary pain (ABP) is yet to be established. The aim of this study was to assess the diagnostic yield and the role of S-MRCP in the investigation of ABP patients. METHODS: This is a retrospective analysis of patients who had S-MRCP to investigate ABP over a 5 year period from June 2008 to May 2013. The findings and diagnosis as reported in the S-MRCP were compared with the findings on MRCP. The primary endpoint was the diagnostic yield of S-MRCP in ABP patients. RESULTS: A total of 117 patients with ABP [28 (24%) male] had S-MRCP during the study period. The most common abnormality identified was obstruction at the level of ampulla or in the proximal pancreatic duct. S-MRCP was able to identify significant pathological findings in 8 of 34 (22%) patients in whom MRCP did not detect any abnormality. Endoscopic ultrasound (EUS) was performed in 67% of patients. S-MRCP identified abnormalities in 21 of 41 (54%) patients who had a normal EUS. CONCLUSIONS: We conclude that the diagnostic yield of S-MRCP for recognizing anatomical variants of the pancreatic ductal system, in particular ampullary or proximal pancreatic duct stricture, is better than MRCP and EUS. These findings reflect the dynamic nature of S-MRCP and its complementary role alongside MRCP, EUS and endoscopic retrograde cholangiopancreatography in ABP patients. PMID- 27366041 TI - Endoscopic management of splenic pseudocysts associated with acute and chronic pancreatitis. AB - BACKGROUND: Splenic pseudocysts (SP) are a rare consequence of both acute and chronic pancreatitis. Surgery has been conventional treatment for SP and literature on role of endoscopic treatment is scant. In this study, we retrospectively evaluated SP clinical and radiological characteristics as well as the outcome following endoscopic drainage. METHODS: Retrospective analysis of SP patients seen at our unit from January 2002 to June 2015. All patients were treated with attempted endoscopic transpapillary drainage with a nasopancreatic drain or stent. Patients not responding underwent endoscopic ultrasound-guided transmural or percutaneous radiological drainage. RESULTS: Eleven patients with SP (all male; mean age: 40.5+/-8.8 years) were studied. Seven patients had chronic pancreatitis and 4 patients had SP following acute pancreatitis. The majority (10/11; 91%) had alcohol-related acute or chronic pancreatitis with one patient having coexistent pancreas divisum. Seven (64%) patients were treated successfully with transpapillary drainage only; one (9%) patient needed combined transpapillary and transmural drainage; and 3 (27%) patients needed surgery. CONCLUSION: Endoscopic transpapillary drainage is an effective treatment for SP especially when it is not infected and with clear contents, and is associated with partial ductal disruption that can be bridged by an endoprosthesis. PMID- 27366042 TI - A bleeding gastric ulcer caused by anisakiasis. PMID- 27366043 TI - Duodenal siderosis: a rare clinical finding in a patient with duodenal inflammation. PMID- 27366044 TI - Resection of a gastric fibroid inflammatory polyp by means of endoscopic submucosal dissection: how deep is deep enough? PMID- 27366045 TI - An isolated colonic neurofibroma. PMID- 27366046 TI - Direct colonoscopic visualization of intrahepatic bile ducts in a post pancreaticoduodenectomy patient. PMID- 27366047 TI - A very unusual cause of dysphagia: mantle cell lymphoma. AB - Dysphagia is an alarm symptom requiring a prompt investigation. Different benign and malignant diseases may present such a symptom. We describe a case of a 79 year-old patient who complained of fluctuating dysphagia episodes following solid food ingestion in the previous 5 months with mild weight loss. No other gastrointestinal symptoms were present. The patient was referred by the General Practitioner for a videofluoroscopic swallow examination which revealed nodularity of mucosa surface in the oropharynx, esophagus, fundus, and gastric body. Upper endoscopy confirmed the feature, also showing a normal mucosa of the antrum and duodenum. The histological examination revealed a mantle cell lymphoma (MCL). A stage III, MCL involving the esophagus and proximal stomach was eventually diagnosed. Esophageal MCL localization is extremely rare, and this is the first report showing a clinical onset with dysphagia. PMID- 27366048 TI - Prospective small bowel mucosal assessment immediately after chemoradiotherapy of unresectable locally advanced pancreatic cancer using capsule endoscopy: a case series. AB - In this case series, three consecutive patients with unresectable locally advanced pancreatic cancer (ULAPC) underwent capsule endoscopy (CE) before and after chemoradiotherapy (CRT) to evaluate duodenal and jejunal mucosa, and to examine the relationship between CE findings and dose distribution. CE after CRT showed duodenitis and proximal jejunitis in all three patients. The most inflamed region was the third part of the duodenum, and in dose distribution, this was the closest region to the center of irradiation. This case series shows that CE can safely diagnose acute duodenitis and proximal jejunitis caused by CRT for ULAPC, and that dose distribution is possible to predict the degree of duodenal and jejunal mucosal injuries. PMID- 27366049 TI - Baseline visual acuity strongly predicts visual acuity gain in patients with diabetic macular edema following anti-vascular endothelial growth factor treatment across trials. AB - OBJECTIVE: This study was designed to evaluate the correlation of baseline visual acuity (VA) with VA outcome in response to anti-vascular endothelial growth factor (VEGF) in diabetic macular edema using a retrospective analysis of nine clinical trials. The result will help assess the relevance of VA gain comparisons across trials. METHODS: A correlation analysis was performed between mean baseline VA and VA gain at month 12 for 1,616 diabetic macular edema patients across nine randomized clinical trials (RESOLVE, RISE, RIDE, RESTORE, RETAIN, DRCR.net Protocol I, DA VINCI, VIVID, VISTA) with anti-VEGF treatment regimens ranibizumab 0.5 mg and aflibercept 2 mg. RESULTS: The mean baseline VA ranged from 56.9 to 64.8 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. The mean VA gain at month 12 ranged from 6.8 to 13.1 ETDRS letters across trials. There was a strong inverse correlation between mean baseline VA and VA gain at month 12 (r=-0.85). The mean VA at 12 months plateaued at ~70 (68.5-73.0) ETDRS letters (20/40 Snellen VA equivalent) for the anti-VEGF treatment groups from all trials, regardless of dosing regimens and agents. CONCLUSION: Cross-trial comparisons based on changes in best-corrected visual acuity should be done cautiously and only after adjusting for best-corrected visual acuity at baseline. Furthermore, the total VA afforded by treatment appears to be subject to a plateau effect, which warrants further exploration. PMID- 27366050 TI - Survey of intravitreal injection techniques among retina specialists in Israel. AB - PURPOSE: The purpose of this study was to describe antivascular endothelial growth factor intravitreal injection techniques of retinal specialists in order to establish a cornerstone for future practice guidelines. METHODS: All members of the Israeli Retina Society were contacted by email to complete an anonymous, 19-question, Internet-based survey regarding their intravitreal injection techniques. RESULTS: Overall, 66% (52/79) completed the survey. Most (98%) do not instruct patients to discontinue anticoagulant therapy and 92% prescribe treatment for patients in the waiting room. Three quarters wear sterile gloves and prepare the patient in the supine position. A majority (71%) use sterile surgical draping. All respondents apply topical analgesics and a majority (69%) measure the distance from the limbus to the injection site. A minority (21%) displace the conjunctiva prior to injection. A majority of the survey participants use a 30-gauge needle and the most common quadrant for injection is superotemporal (33%). Less than half routinely assess postinjection optic nerve perfusion (44%). A majority (92%) apply prophylactic antibiotics immediately after the injection. CONCLUSION: The majority of retina specialists perform intravitreal injections similarly. However, a relatively large minority performs this procedure differently. Due to the extremely low percentage of complications, it seems as though such differences do not increase the risk. However, more evidence-based medicine, a cornerstone for practice guidelines, is required in order to identify the intravitreal injection techniques that combine safety and efficacy while causing as little discomfort to the patients as possible. PMID- 27366051 TI - Macular morphology and response to ranibizumab treatment in patients with wet age related macular degeneration. AB - PURPOSE: The purpose of this study was to assess whether specific characteristics of spectral domain optical coherence tomography (SD-OCT) affect structural and functional outcomes and number of injections needed in ranibizumab (0.05 mL of 10 mg/mL Lucentis solution)-treated wet age-related macular degeneration (AMD) patients. PATIENTS AND METHODS: This retrospective case series included 62 newly diagnosed wet AMD patients treated with three monthly intravitreal ranibizumab injections followed by monthly follow-up and pro re nata retreatment. The presence of dome-shaped pigment epithelial detachment (PED), disruption of the retinal pigment epithelium (RPE), and subretinal and intraretinal fluid was associated with changes in Early Treatment of Diabetic Retinopathy Study visual acuity, central macular thickness (CMT), and number of injections needed during the 6-month follow-up. RESULTS: The presence of PED was associated with lower values of CMT at presentation (399 MUm [+/-132 MUm] vs 310 MUm [+/-51 MUm], P=0.005). The presence of RPE disruption was associated with worse visual acuity in month 6 (0.36 [+/-0.22] vs 0.61 [0.45], P=0.027) and fewer injections (4.23 [+/-0.92] vs 3.55 [+/-0.60], P=0.007). The presence of intraretinal fluid at presentation was associated with worse visual acuity outcomes in month 4 (P=0.045) but not in month 6. CONCLUSION: The dome-shaped PED was associated with lower CMT at presentation, but it did not affect response to treatment. RPE disruption was associated with worse functional outcomes with fewer injections. Intraretinal fluid at presentation may suggest delayed response to treatment. Individualized SD-OCT analysis could lead to individualized approach to wet AMD patients. SD-OCT can offer imaging biomarkers to assess the prognosis of anti VEGF treatment in AMD patients. PMID- 27366052 TI - Prophylactic effects of Clausena excavata Burum. f. leaf extract in ethanol induced gastric ulcers. AB - Clausena excavata is a natural herb with both antioxidant and anti-inflammatory properties. It has been used for decades in folkloric practice for the amelioration of various ailments. In this study, the gastroprotective activity of methanolic extract of C. excavata leaves (MECE) was determined in the Sprague Dawley rat ethanol-induced gastric ulcer model. Rats were pretreated with a single dose of vehicle (5% Tween 20), 20 mg/mL omeprazole, 400 and 200 mg/mL of MECE dissolved in 5% Tween 20. Ulcer was induced with 5 mL/kg of ethanol and stomach tissue was obtained after 1 hour. Histological examination was done on hematoxylin and eosin, periodic acid-Schiff, and immunochemically stained gastric mucosal tissues. Prostaglandin E2, superoxide dismutase, catalase, glutathione peroxidase, and lipid peroxidation levels of the gastric tissue homogenates were also determined. Significantly (P<0.05) smaller ulcer areas, less intense edema, and fewer leukocytes' infiltration were observed in MECE- and omeprazole-treated than in untreated gastric mucosa with ulcer. The gastric pH, mucus production, superoxide dismutase, catalase, and glutathione peroxidase contents increased, while the lipid peroxidation content decreased as a result of MECE treatment. Bcl 2-associated X protein was underexpressed, while heat shock protein 70 and transforming growth factor-beta protein were overexpressed in the ulcerated gastric mucosa tissues treated with omeprazole and MECE. Similarly, there was a reduction in the levels of tumor necrotic factor-alpha and interleukin-6, while the level of interleukin-10 was increased. This study showed that the gastroprotective effect of MECE is achieved through inhibition of gastric juice secretion and ulcer lesion development, stimulation of mucus secretion, elevation of gastric pH, reduction of reactive oxygen species production, inhibition of apoptosis in the gastric mucosa, and modulation of inflammatory cytokines. PMID- 27366053 TI - The association between comorbidities and the quality of life among colorectal cancer survivors in the People's Republic of China. AB - BACKGROUND: Cancer survivors with certain comorbidities had lower quality of life (QOL). This study was performed to investigate the prevalence of comorbidities and the association between comorbidities and the QOL among Chinese colorectal cancer survivors (CCS). METHODS: A cross-sectional study was conducted among 1,398 CCS between April and July 2013 in Shanghai, People's Republic of China. All the participants were asked to complete a simplified Chinese version of the European Organization for Research and Treatment quality of life version 3 questionnaire and questions on sociodemographic characteristics and comorbidities. In order to mitigate the bias caused by confounding factors, multiple linear regression models were employed to calculate the adjusted means of QOL scores. RESULTS: The proportion of participants without any comorbidity was only 20.2%. The CCS with comorbidities except hypertension scored significantly lower on the European Organization for Research and Treatment quality of life version 3 questionnaire global health and functioning scales and Functional Assessment of Cancer Therapy-General scales but higher on the European Organization for Research and Treatment quality of life version 3 questionnaire symptom scores, indicating that they had poorer QOL, particularly for cardiovascular, respiratory, digestive, and musculoskeletal diseases. CONCLUSION: There exists a significant association between comorbidities and QOL among Chinese CCS, and participants with comorbidities generally reported lower QOL scores. These findings suggested comprehensive care for CCS. PMID- 27366054 TI - The impact of using musculoskeletal ultrasound imaging and other influencing factors on medication adherence in patients with rheumatoid arthritis: a qualitative study. AB - BACKGROUND: Medication can ease symptoms and limit disease progression in rheumatoid arthritis (RA). Despite this, nonadherence to medication is common in RA. We explored the determinants of high and low adherence to disease-modifying antirheumatic drugs (DMARDs) in patients with RA and provide suggestions on approaches to improving adherence to DMARDs. METHODS: Patients with RA were identified from those who had previously participated in a questionnaire measuring levels of medication adherence. Twenty patients participated (ten high and ten low adherers, as determined by responses to the Medication Adherence Report Scale). In-depth individual semistructured interviews were undertaken until data saturation was reached. Interviews were transcribed and analyzed using a constant comparative method. RESULTS: Four main themes related to adherence were identified: 1) symptom severity; 2) illness perception; 3) perceived benefits and risks of DMARDs; and 4) the quality and quantity of information about RA and DMARDs. In addition, patients' suggestions about strategies to optimize adherence to DMARDs were captured and they fell within the following themes: 1) musculoskeletal ultrasound to explain the disease process and to provide objective feedback about the extent to which their disease activity is being effectively controlled; 2) better explanations of the consequences of poorly controlled RA; and 3) a good relationship with the health professional. CONCLUSION: Patients' beliefs about medicines, perceptions about RA, and level of satisfaction with information about DMARDs influenced their adherence to DMARDs. The use of musculoskeletal ultrasound to image the inflamed joint may help to improve patient adherence to DMARDs. PMID- 27366055 TI - The development and standardization of Self-assessment for Hearing Screening of the Elderly. AB - PURPOSE: The present study aimed to develop and standardize a screening tool for elderly people who wish to check for themselves their level of hearing loss. METHODS: The Self-assessment for Hearing Screening of the Elderly (SHSE) consisted of 20 questions based on the characteristics of presbycusis using a five-point scale: seven questions covered general issues related to sensorineural hearing loss, seven covered hearing difficulty under distracting listening conditions, two covered hearing difficulty with fast-rated speech, and four covered the working memory function during communication. To standardize SHSE, 83 elderly participants took part in the study: 25 with normal hearing, and 22, 23, and 13 with mild, moderate, and moderate-to-severe sensorineural hearing loss, respectively, according to their hearing sensitivity. All were retested 3 weeks later using the same questionnaire to confirm its reliability. In addition, validity was assessed using various hearing tests such as a sentence test with background noise, a time-compressed speech test, and a digit span test. RESULTS: SHSE and its subcategories showed good internal consistency. SHSE and its subcategories demonstrated high test-retest reliability. A high correlation was observed between the total scores and pure-tone thresholds, which indicated gradually increased SHSE scores of 42.24%, 55.27%, 66.61%, and 78.15% for normal hearing, mild, moderate, and moderate-to-severe groups, respectively. With regard to construct validity, SHSE showed a high negative correlation with speech perception scores in noise and a moderate negative correlation with scores of time-compressed speech perception. However, there was no statistical correlation between digit span results and either the SHSE total or its subcategories. A confirmatory factor analysis supported three factors in SHSE. CONCLUSION: We found that the developed SHSE had valuable internal consistency, test-retest reliability, and convergent and construct validity. These results suggest that SHSE is a reliable and valid measure to represent the degree of hearing loss in the elderly. PMID- 27366056 TI - The association between gastric acid inhibitors and delirium in geriatric inpatients: implications for clinical practice and research. PMID- 27366057 TI - The asthma-COPD overlap syndrome: do we really need another syndrome in the already complex matrix of airway disease? AB - The term asthma-COPD overlap syndrome (ACOS) is one of multiple terms used to describe patients with characteristics of both COPD and asthma, representing ~20% of patients with obstructive airway diseases. The recognition of both sets of morbidities in patients is important to guide practical treatment decisions. It is widely recognized that patients with COPD and coexisting asthma present with a higher disease burden, despite the conceptual expectation that the "reversible" or "treatable" component of asthma would allow for more effective management and better outcomes. However, subcategorization into terms such as ACOS is complicated by the vast spectrum of heterogeneity that is encapsulated by asthma and COPD, resulting in different clinical clusters. In this review, we discuss the possibility that these different clusters are suboptimally described by the umbrella term "ACOS", as this additional categorization may lead to clinical confusion and potential inappropriate use of resources. We suggest that a more clinically relevant approach would be to recognize the extreme variability and the numerous phenotypes encompassed within obstructive airway diseases, with various degrees of overlapping in individual patients. In addition, we discuss some of the evidence to be considered when making practical decisions on the treatment of patients with overlapping characteristics between COPD and asthma, as well as the potential options for phenotype and biomarker-driven management of airway disease with the aim of providing more personalized treatment for patients. Finally, we highlight the need for more evidence in patients with overlapping disease characteristics and to facilitate better characterization of potential treatment responders. PMID- 27366058 TI - Changes in respiratory function impairment following the treatment of severe pulmonary tuberculosis - limitations for the underlying COPD detection. AB - BACKGROUND: During the treatment phase of active pulmonary tuberculosis (PTB), respiratory function impairment is usually restrictive. This may become obstructive, as a PTB-associated airflow obstruction (AFO) or as a later manifestation of underlying COPD. PURPOSE: The aim of the study was to examine the potential causes and risks for AFO development in PTB by exploring the aspects of spirometry limitations and clinical implications for the underlying COPD detection, taking into account various confounding factors. PATIENTS AND METHODS: Prospective, nest case-control study on 40 new cases of PTB with initial restrictive respiratory function impairment, diagnosed and treated according to the directly observed treatment short course (DOTS) strategy. RESULTS: From all observed patients, 37.5% of them developed AFO upon the completion of PTB treatment, with significantly increased average of forced vital capacity (%) (P<0.01). Their changes in forced expiratory volume in the first second (%) during the PTB treatment were strongly associated with the air pollution exposure in living (0.474%-20.971% for 95% confidence interval [CI]; P=0.041) and working environments (3.928%-20.379% for 95% CI; P=0.005), initial radiological extent of PTB lesions (0.018%-0.700% for 95% CI; P=0.047), leukocyte count (0.020%-1.328% for 95% CI; P=0.043), and C-reactive protein serum level (0.046%-0.205% for 95% CI; P=0.003) compared to the other patients. The multivariate logistic regression analysis model shows initial radiological extent of pulmonary tuberculosis lesions (OR 1.01-1.05 for 95% CI; P=0.02) and sputum conversion rate on culture (OR 1.02-1.68 for 95% CI; P=0.04) as the most significant predictors for the risk of AFO development. CONCLUSION: AFO upon PTB treatment is a common manifestation of underlying COPD, which mostly occurs later, during the reparative processes in active PTB, even in the absence of major risk factors, such as cigarette smoking and biomass fuel dust exposure. Initial spirometry testing in patients with active PTB is not a sufficient and accurate approach in the detection of underlying COPD, which may lead to their further potential health deterioration. PMID- 27366059 TI - Prevalence of and risk factors for postoperative pulmonary complications after lung cancer surgery in patients with early-stage COPD. AB - PURPOSE: This study aimed to investigate whether the prevalence of postoperative pulmonary complications (PPCs) in patients with non-small-cell lung cancer (NSCLC) is even higher in the early stages of COPD than in such patients with normal lung function and to verify the usefulness of symptom- or quality of life (QoL)-based scores in predicting risk for PPCs. PATIENTS AND METHODS: Patients undergoing pulmonary resection for NSCLC between July 2012 and October 2014 were prospectively enrolled. Preoperative measurements of lung function, dyspnea, and QoL, operative characteristics, PPCs, duration of postoperative hospitalization, and in-hospital mortality were assessed. RESULTS: Among 351 consecutive patients with NSCLC, 343 patients with forced expiratory volume in 1 second (FEV1) >=70% of predicted value were enrolled. At least one PPC occurred in 57 (16.6%) patients. Prevalence of PPC was higher in patients with COPD (30.1%) than in those with normal spirometry (10.0%; P<0.001). However, in patients with COPD, the prevalence of PPC was not different in patients with FEV1 >=70% compared to those with FEV1 <70% and between group A (low risk and less symptoms) and group B (low risk and more symptoms) patients with COPD, based on the new Global initiative for chronic Obstructive Lung Disease 2011 guidelines. In patients with COPD, body mass index (odds ratio [OR]: 0.80, P=0.007), carbon monoxide diffusing capacity of the lung (DLCO), % predicted value (OR: 0.97, P=0.024), and operation time (OR: 1.01, P=0.003), but not COPD assessment test or St George Respiratory Questionnaire scores, were significantly associated with PPCs. CONCLUSION: Even in patients with early-stage COPD, the prevalence of PPCs is higher than in patients with NSCLC with normal spirometry. However, this rate is not different between group A and group B patients with COPD. In accordance with this, scores based on symptoms or QoL are not predictors of risk of PPCs in patients with early-stage COPD. PMID- 27366060 TI - Factors associated with exacerbation in mild- to-moderate COPD patients. AB - INTRODUCTION: COPD exacerbation negatively impacts the patient's quality of life and lung function, increases mortality, and increases socioeconomic costs. In a real-world setting, the majority of patients with COPD have mild-to-moderate airflow limitation. Therefore, it is important to evaluate COPD exacerbation in patients with mild-to-moderate airflow limitation, although most studies have focused on the patients with moderate or severe COPD. The objective of this study was to evaluate factors associated with COPD exacerbation in patients with mild to-moderate airflow limitation. METHODS: Patients registered in the Korean COPD Subtype Study cohort were recruited from 37 tertiary referral hospitals in Korea. We obtained their clinical data including demographic characteristics, past medical history, and comorbidities from medical records. Patients were required to visit the hospital to document their COPD status using self-administered questionnaires every 6 months. RESULTS: A total of 570 patients with mild-to moderate airflow limitation were enrolled. During the first year of follow-up, 30.5% patients experienced acute exacerbation, with exacerbations being more common in patients with poor lung function. Assessed factors associated with COPD exacerbation included COPD assessment test scores, modified Medical Research Council dyspnea assessment test scores, St George's Respiratory Questionnaire for COPD scores, a previous history of exacerbation, and histories of pneumonia and allergic rhinitis. Logistic regression tests revealed St George's Respiratory Questionnaire for COPD scores (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.00-1.04; P=0.034), a previous history of exacerbation (OR, 3.12; 95% CI, 1.35-7.23; P=0.008), and a history of pneumonia (OR, 1.85; 95% CI, 1.06-3.25; P=0.032) as risk factors for COPD exacerbation. CONCLUSION: Our results suggest that COPD exacerbation in patients with mild-to-moderate airflow limitation is associated with the patient's quality of life, previous history of exacerbation, and history of pneumonia. PMID- 27366061 TI - Amphiphilic core-shell nanoparticles containing dense polyethyleneimine shells for efficient delivery of microRNA to Kupffer cells. AB - Efficient and targeted delivery approach to transfer exogenous genes into macrophages is still a great challenge. Current gene delivery methods often result in low cellular uptake efficiency in vivo in some types of cells, especially for the Kupffer cells (KCs). In this article, we demonstrate that amphiphilic core-shell nanoparticles (NPs) consisting of well-defined hydrophobic poly(methyl methacrylate) (PMMA) cores and branched polyethyleneimine (PEI) shells (denoted as PEI@PMMA NPs) are efficient nanocarriers to deliver microRNA (miRNA)-loaded plasmid to the KCs. Average hydrodynamic diameter of PEI@ PMMA NPs was 279 nm with a narrow size distribution. The NPs also possessed positive surface charges up to +30 mV in water, thus enabling effective condensation of negatively charged plasmid DNA. Gel electrophoresis assay showed that the resultant PEI@PMMA NPs were able to completely condense miRNA plasmid at a weight ratio of 25:1 (N/P ratio equal to 45:1). The Cell Counting Kit-8 assay and flow cytometry results showed that the PEI@PMMA/miRNA NPs displayed low cytotoxicity and cell apoptosis activity against the KCs. The maximum cell transfection efficiency reached 34.7% after 48 hours, which is much higher than that obtained by using the commercial LipofectamineTM 2000 (1.7%). Bio-transmission electron microscope observation revealed that the PEI@PMMA NPs were mainly distributed in the cytoplasm of the KCs. Furthermore, when compared to the control groups, the protein expression of target nuclear factor kappaB P65 was considerably inhibited (P<0.05) both in vitro and in vivo. These results demonstrate that the PEI@PMMA NPs with a unique amphiphilic core-shell nanostructure are promising nanocarriers for delivering miRNA plasmid to KCs. PMID- 27366062 TI - Phytosome-hyaluronic acid systems for ocular delivery of L-carnosine. AB - This study reports on L-carnosine phytosomes as an alternative for the prodrug N acetyl-L-carnosine as a novel delivery system to the lens. L-carnosine was loaded into lipid-based phytosomes and hyaluronic acid (HA)-dispersed phytosomes. L carnosine-phospholipid complexes (PC) of different molar ratios, 1:1 and 1:2, were prepared by the solvent evaporation method. These complexes were characterized with thermal and spectral analyses. PC were dispersed in either phosphate buffered saline pH 7.4 or HA (0.1% w/v) in phosphate buffered saline to form phytosomes PC1:1, PC1:2, and PC1:2 HA, respectively. These phytosomal formulations were studied for size, zeta potential, morphology, contact angle, spreading coefficient, viscosity, ex vivo transcorneal permeation, and cytotoxicity using primary human corneal cells. L-carnosine-phospholipid formed a complex at a 1:2 molar ratio and phytosomes were in the size range of 380-450 nm, polydispersity index of 0.12-0.2. The viscosity of PC1:2 HA increased by 2.4 to 5 fold compared with HA solution and PC 1:2, respectively; significantly lower surface tension, contact angle, and greater spreading ability for phytosomes were also recorded. Ex vivo transcorneal permeation parameters showed significantly controlled corneal permeation of L-carnosine with the novel carrier systems without any significant impact on primary human corneal cell viability. Ex vivo porcine lenses incubated in high sugar media without and with L-carnosine showed concentration-dependent marked inhibition of lens brunescence indicative of the potential for delaying changes that underlie cataractogenesis that may be linked to diabetic processes. PMID- 27366063 TI - Development of self-nanoemulsifying drug delivery systems for the enhancement of solubility and oral bioavailability of fenofibrate, a poorly water-soluble drug. AB - BACKGROUND: Self-nanoemulsifying drug delivery systems (SNEDDS) have become a popular formulation option as nanocarriers for poorly water-soluble drugs. The objective of this study was to investigate the factor that can influence the design of successful lipid formulation classification system (LFCS) Type III SNEDDS formulation and improve the oral bioavailability (BA) of fenofibrate. MATERIALS AND METHODS: LFCS Type III SNEDDS were designed using various oils, water-soluble surfactants, and/or cosolvents (in considering the polarity of the lipids) for the model anticholesterol drug, fenofibrate. The developed SNEDDS were assessed visually and by measurement of the droplet size. Equilibrium solubility of fenofibrate in the SNEDDS was conducted to find out the maximum drug loading. Dynamic dispersion studies were carried out (1/100 dilution) in water to investigate how much drug stays in solution after aqueous dispersion of the formulation. The BA of SNEDDS formulation was evaluated in the rat. RESULTS: The results from the characterization and solubility studies showed that formulations containing mixed glycerides were highly efficient SNEDDS as they had higher solubility of the drug and produced nanosized droplets. The dispersion studies confirmed that SNEDDS (containing polar mixed glycerides) can retain >98% drug in solution for >24 hours in aqueous media. The in vivo pharmacokinetics parameters of SNEDDS formulation in comparison with pure drug showed significant increase in C max and AUC0- t , ~78% and 67%, respectively. The oral BA of fenofibrate from SNEDDS in rats was ~1.7-fold enhanced as compared with the BA from pure drug. CONCLUSION: Fenofibrate-loaded LFCS Type III SNEDDS formulations could be a potential oral pharmaceutical product for administering the poorly water-soluble drug, fenofibrate, with an enhanced oral BA. PMID- 27366064 TI - Transformation of eutectic emulsion to nanosuspension fabricating with solvent evaporation and ultrasonication technique. AB - Eutectic solvent can solubilize high amount of some therapeutic compounds. Volatile eutectic solvent is interesting to be used as solvent in the preparation of nanosuspension with emulsion solvent evaporation technique. The mechanism of transformation from the eutectic emulsion to nanosuspension was investigated in this study. The 30% w/w ibuprofen eutectic solution was used as the internal phase, and the external phase is composed of Tween 80 as emulsifier. Ibuprofen nanosuspension was prepared by eutectic emulsion solvent evaporating method followed with ultrasonication. During evaporation process, the ibuprofen concentration in emulsion droplets was increased leading to a drug supersaturation but did not immediately recrystallize because of low glass transition temperature (T g) of ibuprofen. The contact angle of the internal phase on ibuprofen was apparently lower than that of the external phase at all times of evaporation, indicating that the ibuprofen crystals were preferentially wetted by the internal phase than the external phase. From calculated dewetting value ibuprofen crystallization occurred in the droplet. Crystallization of the drug was initiated with external mechanical force, and the particle size of the drug was larger due to Ostwald ripening. Cavitation force from ultrasonication minimized the ibuprofen crystals to the nanoscale. Particle size and zeta potential of formulated ibuprofen nanosuspension were 330.87+/-51.49 nm and 31.1+/-1.6 mV, respectively, and exhibited a fast dissolution. Therefore, the combination of eutectic emulsion solvent evaporation method with ultrasonication was favorable for fabricating an ibuprofen nanosuspension, and the transformation mechanism was attained successfully. PMID- 27366065 TI - A brief perspective on the diverging theories of lymphatic targeting with colloids. AB - For targeted delivery of colloids to the lymphatic system, the colloids should efficiently reach and remain in the lymphatics for a considerable period of time. As per the current knowledge, diffusion and phagocytosis are the two mechanisms through which colloids reach the lymphatic system. Several parameters including particle size and charge have been shown to affect the direct uptake of colloids by the lymphatic system. Although many researchers attached ligands on the surface of colloids to promote phagocytosis-mediated lymphatic delivery, another school of thought suggests avoidance of phagocytosis by use of carriers like polyethylene glycol (PEG)ylated colloids to impart stealth attributes and evade phagocytosis. In this perspective, we weigh up the paradoxical theories and approaches available in the literature to draw conclusions on the conditions favorable for achieving efficient lymphatic targeting of colloids. PMID- 27366066 TI - Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats. AB - Despite widespread use and prospective biomedical applications of copper nanoparticles (Cu NPs), their biosafety issues and kinetics remain unclear. Thus, the aim of this study was to compare the detailed in vivo toxicity of Cu NPs and cupric ions (CuCl2; Cu ions) after a single oral dose. We determined the physicochemical characteristics of Cu NPs, including morphology, hydrodynamic size, zeta potential, and dissolution in gastric (pH 1.5), vehicle (pH 6.5), and intestinal (pH 7.8) conditions. We also evaluated the kinetics of Cu following a single equivalent dose (500 mg/kg) of Cu NPs and Cu ions. Cu NPs had highest dissolution (84.5%) only in gastric conditions when compared with complete dissolution of Cu ions under various physiological milieus. Kinetic analysis revealed that highest Cu levels in blood and tested organs of Cu NP-treated rats were 15%-25% lower than that of Cu ions. Similar to the case of Cu ions, Cu levels in the tested organs (especially liver, kidney, and spleen) of Cu NP treated rats increased significantly when compared with the vehicle control. However, delay in reaching the highest level and biopersistence of Cu were observed in the blood and tested organs of Cu NP-treated rats compared with Cu ions. Extremely high levels of Cu in feces indicated that unabsorbed Cu NPs or absorbed Cu ions were predominantly eliminated through liver/feces. Cu NPs exerted apparent toxicological effects at higher dose levels compared with Cu ions and showed sex-dependent differences in mortality, biochemistry, and histopathology. Liver, kidney, and spleen were the major organs affected by Cu NPs. Collectively, the toxicity and kinetics of Cu NPs are most likely influenced by the release of Cu dissociated from Cu NPs under physiological conditions. PMID- 27366067 TI - The effect of ApoE e4 on blood pressure in patients with and without depression. AB - INTRODUCTION: Depression is considered an independent risk factor for hypertension, particularly for people with recurrent episodes or a long history of depression. Another risk factor for cardiovascular disease is the Apolipoprotein E e4 allele (ApoE e4). The aim of this study was to examine how ApoE e4 was related to blood pressure (BP) in patients with depression and a control group. METHODS: A total of 78 patients, 49 with depression and 29 without, all recruited from the same hospital, underwent ApoE e genotyping (24 had at least one ApoE e4 allele) and examination of BP. RESULTS: In the depression group, but not in the control group, both systolic and diastolic BP were significantly higher in patients with ApoE e4 than in those without. The effect of ApoE e4 on BP differed significantly between the two groups. CONCLUSION: Our findings showed that the effect of ApoE e4 on BP differed between the patients with depression and the control group. In patients with depression, ApoE e4 was associated with an increase in BP. We suggest that patients with depression and ApoE e4-positive status are particularly prone to develop BP elevation. PMID- 27366068 TI - Abnormal spontaneous regional brain activity in primary insomnia: a resting-state functional magnetic resonance imaging study. AB - OBJECTIVE: Investigating functional specialization is crucial for a complete understanding of the neural mechanisms of primary insomnia (PI). Resting-state functional magnetic resonance imaging (fMRI) is a useful tool to explore the functional specialization of PI. However, only a few studies have focused on the functional specialization of PI using resting-state fMRI and results of these studies were far from consistent. Thus, the current study aimed to investigate functional specialization of PI using resting-state fMRI with amplitude of low frequency fluctuations (ALFFs) algorithm. METHODS: In this study, 55 PI patients and 44 healthy controls were included. ALFF values were compared between the two groups using two-sample t-test. The relationship of abnormal ALFF values with clinical characteristics and duration of insomnia was investigated using Pearson's correlation analysis. RESULTS: PI patients showed lower ALFF values in the left orbitofrontal cortex/inferior frontal gyrus, right middle frontal gyrus, left inferior parietal lobule, and bilateral cerebellum posterior lobes, while higher ALFF values in the right middle/inferior temporal that extended to the right occipital lobe. In addition, we found that the duration of PI negatively correlated with ALFF values in the left orbitofrontal cortex/inferior frontal gyrus, and the Pittsburgh Sleep Quality Index score negatively correlated with ALFF values in the left inferior parietal lobule. CONCLUSION: The present study added information to limited studies on functional specialization and provided evidence for hyperarousal hypothesis in PI. PMID- 27366069 TI - Early diagnosis and Early Start Denver Model intervention in autism spectrum disorders delivered in an Italian Public Health System service. AB - BACKGROUND: Early diagnosis combined with an early intervention program, such as the Early Start Denver Model (ESDM), can positively influence the early natural history of autism spectrum disorders. This study evaluated the effectiveness of an early ESDM-inspired intervention, in a small group of toddlers, delivered at low intensity by the Italian Public Health System. METHODS: Twenty-one toddlers at risk for autism spectrum disorders, aged 20-36 months, received 3 hours/wk of one-to-one ESDM-inspired intervention by trained therapists, combined with parents' and teachers' active engagement in ecological implementation of treatment. The mean duration of treatment was 15 months. Cognitive and communication skills, as well as severity of autism symptoms, were assessed by using standardized measures at pre-intervention (Time 0 [T0]; mean age =27 months) and post-intervention (Time 1 [T1]; mean age =42 months). RESULTS: Children made statistically significant improvements in the language and cognitive domains, as demonstrated by a series of nonparametric Wilcoxon tests for paired data. Regarding severity of autism symptoms, younger age at diagnosis was positively associated with greater improvement at post-assessment. CONCLUSION: Our results are consistent with the literature that underlines the importance of early diagnosis and early intervention, since prompt diagnosis can reduce the severity of autism symptoms and improve cognitive and language skills in younger children. Particularly in toddlers, it seems that an intervention model based on the ESDM principles, involving the active engagement of parents and nursery school teachers, may be effective even when the individual treatment is delivered at low intensity. Furthermore, our study supports the adaptation and the positive impact of the ESDM entirely sustained by the Italian Public Health System. PMID- 27366070 TI - Recognized homonymous hemianopsia and delirium during the admission examination leading to diagnosis and appropriate treatment of a new stroke. AB - This case report describes the detection of homonymous hemianopsia and delirium during the admission physical examination of a patient with esophageal adenocarcinoma, resulting in the new diagnosis of subacute hemorrhagic stroke. The poststroke visual field defect can result in significant disability and reduction in quality of life. Patients with visual field cut show a severely reduced quality of life and require additional neuropsychological and visual rehabilitation. Only thorough physical examination is able to challenge prior negative positron emission tomography scan, leading to the diagnosis of subacute stroke and, following appropriate treatment, secondary stroke prophylaxis and rehabilitation, instead of brain radiation and chemotherapy. PMID- 27366071 TI - Levels of serum immunomodulators and alterations with electroconvulsive therapy in treatment-resistant major depression. AB - Studies in recent years have indicated that neuroimmunological events and immune activation may have a place in the etiology of depression. It has been suggested from data that there is a causal relationship between activation of the immune system and excessive release of proinflammatory cytokines, such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-alpha), and the etiology of depression. Although the mechanism of action of electroconvulsive therapy (ECT) is unclear, there is evidence that it can reduce cytokines and immune system changes. In our study, we aimed to determine how levels of serum immunomodulators were affected by ECT in major depression patients. This study was conducted on 50 patients with treatment-resistant major depression. The data of the patients were compared with 30 healthy individuals with similar demographic characteristics. A clinical response occurred in the patients and at the end of therapy, IL-1, IL-6, TNF-alpha, IL-10, IL-4, and interferon-gamma levels were measured. The disease severity was assessed with the 17-item Hamilton Depression Rating Scale. Data analysis was performed using SPSS Version 15. Significant differences were determined between the patients with major depression and control group with respect to basal serum IL-1, IL-6, TNF-alpha, IL-10, IL-4, and interferon-gamma levels. ECT treatment was shown to reduce these differences. ECT may cause significant changes in the activity of the immune system. The consideration of the relationship between the immune endocrine neurotransmitter systems could contribute to new theories regarding the mechanism of antidepressant treatment and biology of depression. PMID- 27366072 TI - Anterior cingulate hyperactivations during negative emotion processing among men with schizophrenia and a history of violent behavior. AB - BACKGROUND: Evidence suggests a 2.1-4.6 times increase in the risk of violent behavior in schizophrenia compared to the general population. Current theories propose that the processing of negative emotions is defective in violent individuals and that dysfunctions within the neural circuits involved in emotion processing are implicated in violence. Although schizophrenia patients show enhanced sensitivity to negative stimuli, there are only few functional neuroimaging studies that have examined emotion processing among men with schizophrenia and a history of violence. OBJECTIVE: The present study aimed to identify the brain regions with greater neurofunctional alterations, as detected by functional magnetic resonance imaging during an emotion processing task, of men with schizophrenia who had engaged in violent behavior compared with those who had not. METHODS: Sixty men were studied; 20 with schizophrenia and a history of violence, 19 with schizophrenia and no violence, and 21 healthy men were scanned while viewing positive, negative, and neutral images. RESULTS: Negative images elicited hyperactivations in the anterior cingulate cortex (ACC), left and right lingual gyrus, and the left precentral gyrus in violent men with schizophrenia, compared to nonviolent men with schizophrenia and healthy men. Neutral images elicited hyperactivations in the right and left middle occipital gyrus, left lingual gyrus, and the left fusiform gyrus in violent men with schizophrenia, compared to the other two groups. DISCUSSION: Violent men with schizophrenia displayed specific increases in ACC in response to negative images. Given the role of the ACC in information integration, these results indicate a specific dysfunction in the processing of negative emotions that may trigger violent behavior in men with schizophrenia. PMID- 27366073 TI - Self-perceived cognitive deficits and their relationship with internalized stigma and quality of life in patients with schizophrenia. AB - BACKGROUND: We investigated self-perceived cognitive deficits and their relationship with internalized stigma and quality of life in patients with schizophrenia in order to shed light on the clinical correlates of subjective cognitive deficits in schizophrenia. METHODS: Seventy outpatients with schizophrenia were evaluated. Patients' self-perceived cognitive deficits, internalized stigma, and subjective quality of life were assessed using the Scale to Investigate Cognition in Schizophrenia (SSTICS), the Internalized Stigma of Mental Illness Scale (ISMI), and the Schizophrenia Quality of Life Scale Revision 4 (SQLS-R4), respectively. Correlation and regression analyses controlling for the severity of symptoms of schizophrenia were performed, and a mediation analysis was conducted to examine the hypothesis that internalized stigma mediates the relationship between self-perceived cognitive deficits and subjective quality of life. RESULTS: Pearson's partial correlation analysis showed significant correlations among the SSTICS, ISMI, and SQLS-R4 scores (P<0.01). Multiple regression analysis showed that the SSTICS and ISMI scores significantly predicted the SQLS-R4 score (P<0.01). Mediation analysis revealed that the strength of the association between the SSTICS and SQLS-R4 scores decreased from beta=0.74 (P<0.01) to beta=0.56 (P<0.01), when the ISMI score was statistically controlled. The Sobel test revealed that this difference was significant (P<0.01), indicating that internalized stigma partially mediated the relationship between self-perceived cognitive deficits and quality of life. CONCLUSION: The present study indicates that self-perceived cognitive deficits are significantly associated with internalized stigma and quality of life. Furthermore, internalized stigma was identified as a partial mediator of the relationship between self-perceived cognitive deficits and quality of life. These findings suggest that clinicians should be aware that patients with schizophrenia experience significantly greater self-stigma when they suffer subjective cognitive deficits, and that this may further compromise their quality of life. PMID- 27366074 TI - Body integrity identity disorder crosses culture: case reports in the Japanese and Chinese literature. AB - Body integrity identity disorder (BIID) is a condition in which people do not perceive a part of their body as their own, which results in a strong desire for amputation or paralyzation. The disorder is likely to be congenital due to its very early onset. The English literature describes only Western patients with BIID, suggesting that the disorder might be merely prevalent in the West. To scrutinize this assumption, and to extend our knowledge of the etiology of BIID, it is important to trace cases with BIID in non-Western populations. Our objective was to review Chinese and Japanese literature on BIID to learn about its presence in populations with a different genetic background. A systematic literature search was performed in databases containing Japanese and Chinese research, published in the respective languages. Five Japanese articles of BIID were identified which described two cases of BIID, whereas in the Chinese databases only BIID-related conditions were found. This article reports some preliminary evidence that BIID is also present in non-Western countries. However, making general statements about the biological background of the disorder is hampered by the extremely low number of cases found. This low number possibly resulted from the extreme secrecy associated with the disorder, perhaps even more so in Asian countries. PMID- 27366075 TI - Mesalazine-induced eosinophilic pneumonia with bone marrow infiltration: a case report and literature review. AB - Mesalazine-induced eosinophilic pneumonia has been rarely reported. We reported a case of mesalazine-induced eosinophilic pneumonia in a 56-year-old female who took mesalazine without a prescription for suspected ulcerative colitis. She had an elevated eosinophil count in peripheral blood and bronchoalveolar lavage fluid. Eosinophil infiltration was also noted in bone marrow aspirates. Chest radiograph and computed tomography demonstrated bilateral upper lung predominant infiltrates and spirometry showed a restrictive ventilatory defect with a reduced diffusion capacity. The patient recovered after cessation of mesalazine therapy. Mesalazine-induced lung damage should be considered in patients who develop unexplained respiratory symptoms while taking this agent. PMID- 27366076 TI - Prescription of antibiotics in community-acquired pneumonia in children: are we following the recommendations? AB - OBJECTIVE: To assess the adequacy of antibiotic prescription in children hospitalized for pneumonia in a reference pediatric hospital in Brazil. METHODS: This was a cross-sectional study involving children aged between 1 month and 5 years who were hospitalized between October 2010 and September 2013. The classification of community-acquired pneumonia (CAP) was based on the clinical and radiological criteria of the World Health Organization (WHO). The analysis of antibiotic adequacy was performed according to the main guidelines on CAP treatment, which include the WHO guidelines, Brazilian Society of Pediatrics guidelines, and international guidelines (Pediatrics Infectious Diseases Society, the Infectious Disease Society of America, British Thoracic Society, and Consenso de la Sociedad latinoamericana de Infectologia). A multivariate analysis was performed including variables that have statistical significance of P<=0.25 in the bivariate analysis. RESULTS: The majority of the 452 hospitalized children were classified as having severe or very severe CAP (85.18%), and inadequate empiric antimicrobial therapy was started in 26.10% (118/452) of them. Ampicillin was the most used empiric antibiotic therapy (62.17%) for pneumonia, followed by a combination of ampicillin and associated with gentamicin. The initially proposed regimen was modified in 29.6% of the patients, and the most frequent change was the replacement of ampicillin by oxacillin combined with chloramphenicol. The median hospitalization time was 8.5 days, and the lethality rate was 1.55%. There was no statistical difference in adequacy in relation to the severity of pneumonia or degree of malnutrition. In the bivariate analysis, inadequacy of antibiotic therapy regimen was higher in patients undergoing oxygen therapy (P<0.05), which was given to 219 patients (48.45%). Pleural effusion was observed in 118 patients (26.11%) and was associated with higher prescription inadequacy, and it was the only factor that remained in the multivariate analysis (odds ratio =8.89; 95% confidence interval 5.20-15.01). CONCLUSION: Adherence to the main guidelines for antimicrobial therapy according to the childhood CAP was unsatisfactory. Compliance with the guidelines is essential for both the management of pneumonia cases and the decrease in bacterial resistance and it is one of the cornerstone of WHO police of controlling antibiotic resistance. PMID- 27366077 TI - Occupational HIV risk for health care workers: risk factor and the risk of infection in the course of professional activities. AB - Virtually created panic among health care workers about pandemic acquired immune deficiency syndrome prompted us to review the scientific literature to investigate the risk of human immunodeficiency virus (HIV) transmission in the daily works of health care workers, especially surgeons and anesthesiologists. In this review, we report worldwide valuations of the number of HIV infections that may occur from unsafe daily work in health care. We also present how to minimize the risk of infection by taking precautions and how to utilize postexposure prophylaxis in accordance with the latest reports of the Centers for Disease Control and Prevention. HIV-infected patients will be aging, and most of them will become the candidates for procedures such as major vascular reconstruction and artery bypass grafting, where the risks of blood contact and staff injury are high. For these reasons, all health care workers need to know how to prevent, and fight following the accidental exposure to HIV. PMID- 27366078 TI - Value of cyst localization to predict cystobiliary communication in patients undergoing conservative surgery with hydatid cyst. AB - OBJECTIVE: The objectives of this study were to investigate the relationship between the segmental localization of liver hydatid cyst by computed tomography (CT) and the presence of cystobiliary communication (CBC) and to identify the risk factors for CBC. PATIENTS AND METHODS: One hundred and eleven of 163 patients who underwent liver hydatid surgery between January 2011 and September 2014 were included in this study and analyzed retrospectively. The size, number, stage, and segmental and lobar localization of the cysts were investigated by CT. The presence of CBC and preoperative laboratory findings were recorded from operation notes. RESULTS: CBC was more frequent in single large cysts. CBC was most commonly detected in segment 1 (50%), 8 (48.3%), 7 (41.2%), and 4 (40%). CBC was more frequent in the right lobe (40.4%) and Gharbi stage 3 (41.8%) and 4 (55.6%) lesions. There were no differences in CBC according to distance from the hilus. In addition, preoperative total bilirubin, direct bilirubin, alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) elevations were associated with higher CBC frequency (P<0.05). Cyst diameter, number of cysts, and ALP and GGT elevations were independent predictors of CBC presence. CONCLUSION: The evaluation of hydatid cyst diameter, morphological stage, and segmental and lobar localization by abdominal CT and measurement of preoperative cyst diameter, number of cysts, and ALP and GGT values may predict the presence of CBC. PMID- 27366079 TI - Direct thrombolysis of multiple thrombi in both right and left heart atrium in a patient on extracorporeal membrane oxygenation support following urgent double lung transplantation: a case report. AB - BACKGROUND: Lung transplantation is considered an established treatment for patients with end-stage chronic respiratory failure. Patients with acute respiratory failure requiring respiratory support with invasive mechanical ventilation while awaiting lung transplantation are at high risk of death. Extracorporeal membrane oxygenation (ECMO) has been proposed as an alternative bridging strategy to mechanical ventilation. The shear stress created by the mechanical pumps causes changes in the hematological system in almost all patients treated with ECMO. An antithrombotic strategy to mitigate ECMO bleeding and thrombotic complications is necessary. The use of thrombolytic therapy is recommended for patients with acute symptomatic embolism with associated hypotension or shock. In this setting, the hemodynamic benefits of thrombolytic treatment far outweigh its bleeding risk. CASE PRESENTATION: This case report describes a 32-year-old woman suffering from lymphangioleiomyomatosis, who underwent urgent double-lung transplantation. This patient was maintained on ECMO preoperatively, perioperatively, and postoperatively due to life-threatening hypoxemia caused by the progression of her pulmonary tissue damage. Multiple thrombi developed in the early postoperative period, in both right and left heart atria. Direct thrombolysis was successfully performed on the first postoperative day. CONCLUSION: According to the current published literature, direct thrombolysis of thrombi in both right and left atria in a patient supported on ECMO following urgent double-lung transplantation is an extremely rare treatment method. Even when taking into account all of the risks associated with thrombolysis and arteriovenous ECMO support, we found that this technique is very effective and, without a doubt, it saved the life of our patient. PMID- 27366080 TI - Men with testosterone deficiency and a history of cardiovascular diseases benefit from long-term testosterone therapy: observational, real-life data from a registry study. AB - BACKGROUND/OBJECTIVES: Long-term testosterone therapy (TTh) in men with hypogonadism has been shown to improve all components of the metabolic syndrome. In this study, we investigated the effects of long-term TTh up to 8 years in hypogonadal men with a history of cardiovascular disease (CVD). PATIENTS AND METHODS: In two urological clinics observational registries, we identified 77 hypogonadal men receiving TTh who also had a history of CVD. The effects of TTh on anthropometric and metabolic parameters were investigated for a maximum duration of 8 years. Any occurrence of major adverse cardiovascular events was reported. All men received long-acting injections of testosterone undecanoate at 3-monthly intervals. RESULTS: In 77 hypogonadal men with a history of CVD who received TTh, we observed a significant weight loss and a decrease in waist circumference and body mass index. Mean weight decreased from 114+/-13 kg to 91+/ 9 kg, change from baseline: -24+/-1 kg and -20.2%+/-0.5%. Waist circumference decreased from 112+/-8 cm to 99+/-6 cm, change from baseline: -13+/-0.3 cm. Body mass index decreased from 37+/-4 to 29+/-3, change from baseline: -8+/-0.2 kg/m(2). Cardio-metabolic parameters such as lipid pattern, glycemic control, blood pressure, heart rate, and pulse pressure all improved significantly and sustainably. No patient suffered a major adverse cardiovascular event during the full observation time. CONCLUSION: In men with hypogonadism, TTh appears to be effective in achieving sustained improvements in all cardiometabolic risk factors and may be effective as an add-on measure in the secondary prevention of cardiovascular events in hypogonadal men with a history of CVD. PMID- 27366081 TI - Impact of selective platelet inhibition in reducing cardiovascular risk - role of vorapaxar. AB - This article reviews the pharmacology, clinical efficacy, and safety of vorapaxar in reducing cardiovascular risk. Vorapaxar is a tricyclic himbacine-derived reversible inhibitor of platelet surface protease activator receptor-1, which prevents thrombin from activating platelets. Two Phase III clinical trials and multiple subanalyses from the two trials with vorapaxar have been published. In patients with recent acute coronary syndrome, vorapaxar, when added to standard therapy, did not reduce the composite cardiovascular end point. In contrary, in a study of secondary prevention for patients with cardiovascular diseases, vorapaxar reduced the risk of cardiovascular death or ischemic events (myocardial infarction, stroke) in patients with stable atherosclerosis who were receiving standard therapy. Vorapaxar is approved in the US for use with aspirin and/or clopidogrel in the secondary prevention of thrombogenic cardiovascular events in stable patients with peripheral arterial disease or a history of myocardial infarction. Vorapaxar increases risk of bleeding and is contraindicated in patients with previous cerebrovascular events. It is essential to balance individual patient's bleeding risk to any further cardiovascular benefits that they may get. Future investigation is also needed to evaluate use of vorapaxar with newer antiplatelet agents such as ticagrelor and cangrelor, as well as its role as monotherapy. PMID- 27366082 TI - Transcription factor activity of estrogen receptor alpha activation upon nonylphenol or bisphenol A treatment enhances the in vitro proliferation, invasion, and migration of neuroblastoma cells. AB - Many kinds of endocrine-disrupting chemicals (EDCs), for example, the environmental estrogens bisphenol A and nonylphenol, may regulate the activity of estrogen receptor alpha (ERalpha) and therefore induce potential disruption of normal endocrine function. However, the involvement of EDCs in human cancers, especially in endocrine-related cancer neuroblastoma regulation, is not very clear. In this work, results showed that upon bisphenol A or nonylphenol treatment, the transcription factor activity of ERalpha was significantly increased in neuroblastoma cell line SH-SY5Y. Bisphenol A and nonylphenol could enhance ERalpha activity via recruiting it to the target gene promoter. Furthermore, treatment of bisphenol A and nonylphenol enhanced the in vitro proliferation, invasion, and migration ability of neuroblastoma cells. By investigating the role of EDC-induced ERalpha upregulation, our data extend the understanding of the function of EDCs and further suggest that ERalpha might be a potential therapeutic target in human neuroblastoma treatment. PMID- 27366083 TI - The expression of ERCC1 and BRCA1 predicts prognosis of platinum-based chemotherapy in urothelial cancer. AB - OBJECTIVE: To investigate the expression and clinical significance of ERCC1 and BRCA1 genes in urothelial cancer patients. METHODS: Forty-two urothelial cancer patients who did not receive platinum-based chemotherapy during January 2009 to May 2013 were enrolled. The expression levels of ERCC1 and BRCA1 were determined by immunohistochemistry and the median survival time (MST) for these patients was calculated. RESULTS: ERCC1-positive patients who received oxaliplatin-based chemotherapy had a shorter MST than ERCC1-negative patients (P<0.05), whereas there is no difference of MST between BRCA1-positive and -negative patients. Furthermore, MST in ERCC1 and BRCA1 double-positive patients was shorter than ERCC1 and BRCA1 double-negative patients (P<0.05). The positive expression of ERCC1 had a significant positive correlation with BRCA1 (r=0.313, P=0.044). CONCLUSION: The expression level of ERCC1 may be used as a prognostic marker for urothelial cancer patients who received postoperative adjuvant chemotherapy. PMID- 27366084 TI - Function of AURKA protein kinase in the formation of vasculogenic mimicry in triple-negative breast cancer stem cells. AB - Tumor cell vasculogenic mimicry (VM), a newly defined pattern of tumor blood supply, signifies the functional plasticity of aggressive cancer cells forming vascular networks. VM and cancer stem cells (CSCs) have been shown to be associated with tumor growth, local invasion, and distant metastasis. In our previous study, CSCs in triple-negative breast cancer were potential to participate in VM formation. In this study, breast CSCs were isolated from the triple-negative breast cancer cell line MDA-MB-231 by using mammosphere culture. Western blotting and reverse transcription polymerase chain reaction showed that mammosphere cells displayed an increased expression of AURKA protein kinase and stem cell marker c-myc and sox2. The VM formation by mammosphere cells was inhibited by AURKA knockdown or the addition of AURKA inhibitor MLN8237. In the meantime, MLN8237 induced the increased E-cadherin and decreased c-myc, sox2, and beta-catenin expressions. The function of AURKA in VM formation was further confirmed using a xenograft-murine model. The results suggested that AURKA protein kinase is involved in VM formation of CSCs and may become a new treatment target in suppressing VM and metastasis of breast cancer. PMID- 27366085 TI - PTEN gene mutations correlate to poor prognosis in glioma patients: a meta analysis. AB - BACKGROUND: We conducted this meta-analysis based on eligible trials to investigate the relationship between phosphatase and tensin homolog (PTEN) genetic mutation and glioma patients' survival. METHODS: PubMed, Web of Science, and EMBASE were searched for eligible studies regarding the relationship between PTEN genetic mutation and glioma patients' survival. The primary outcome was the overall survival of glioma patient with or without PTEN genetic mutation, and second outcome was prognostic factors for the survival of glioma patient. A fixed effects or random-effects model was used to pool the estimates according to the heterogeneity among the included studies. RESULTS: Nine cohort studies, involving 1,173 patients, were included in this meta-analysis. Pooled results suggested that glioma patients with PTEN genetic mutation had a significant shorter overall survival than those without PTEN genetic mutation (hazard ratio [HR] =2.23, 95% confidence interval [CI]: 1.35, 3.67; P=0.002). Furthermore, subgroup analysis indicated that this association was only observed in American patients (HR =2.19, 95% CI: 1.23, 3.89; P=0.008), but not in Chinese patients (HR =1.44, 95% CI: 0.29, 7.26; P=0.657). Histopathological grade (HR =1.42, 95% CI: 0.07, 28.41; P=0.818), age (HR =0.94, 95% CI: 0.43, 2.04; P=0.877), and sex (HR =1.28, 95% CI: 0.55, 2.98; P=0.564) were not significant prognostic factors for the survival of patients with glioma. CONCLUSION: Current evidence indicates that PTEN genetic mutation is associated with poor prognosis in glioma patients. However, this finding is derived from data in observational studies, potentially subject to selection bias, and hence well conducted, high-quality randomized controlled trials are warranted. PMID- 27366086 TI - Positive association between CD44 gene rs13347 C>T polymorphism and risk of cancer in Asians: a systemic review and meta-analysis. AB - BACKGROUND: Cluster of differentiation 44 (CD44) is an important surface marker of cancer stem cells in a variety of tumors. A number of previous studies have been conducted to investigate the association between CD44 gene rs13347 C>T polymorphism and cancer risk in humans; nevertheless, the results remain controversial. We therefore performed this meta-analysis to confirm the role of this polymorphism in susceptibility to human cancer. MATERIALS AND METHODS: The studies published up to December 2015 were searched in PubMed, Web of Science, and China National Knowledge Infrastructure databases. Twelve eligible case control studies were identified, involving a total of 6,982 cases and 7,430 controls. Pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated using a fixed or random-effect model to estimate the strength of the association. RESULTS: The results of the overall analyses indicated that CD44 gene rs13347 polymorphism was significantly associated with cancer risk in Asians (CT vs CC: OR =1.35, 95% CI =1.12-1.62; TT vs CC: OR =1.99, 95% CI =1.52-2.60; TT + CT vs CC: OR =1.41, 95% CI =1.16-1.71; and TT vs CC + CT: OR =1.74, 95% CI =1.41-2.14), especially in Chinese population (CT vs CC: OR =1.42, 95% CI =1.16 1.75; TT vs CC: OR =2.13, 95% CI =1.58-2.86; TT + CT vs CC: OR =1.50, 95% CI =1.21-1.87; and TT vs CC + CT: OR =1.80, 95% CI =1.43-2.26). In stratified analyses by cancer types, there was evidence for an association between this polymorphism and nasopharyngeal cancer and breast cancer, respectively. CONCLUSION: The results of this meta-analysis suggest that the CD44 gene rs13347 C>T polymorphism is associated with elevated risk of human cancer in Asians, especially in Chinese population. Further well-designed studies on a larger population covering other ethnicities should be carried out to validate our results. PMID- 27366087 TI - Knockdown of long noncoding RNA H19 sensitizes human glioma cells to temozolomide therapy. AB - Temozolomide (TMZ) is commonly used in glioma chemotherapy. However, a great clinical challenge for TMZ is chemoresistance. H19 transcripts are recognized as long noncoding RNAs, which potentially interact with chromatin-modifying complexes to regulate gene expression via epigenetic changes. Our data based on glioma patients showed that the expression of H19 was significantly upregulated in TMZ-resistant tumors compared with the TMZ-sensitive tumors. To determine the function of H19 in glioma, cell lines U87 and U251 were exposed to TMZ to establish TMZ-resistant clones U87(TMZ) and U251(TMZ). In U87(TMZ) and U251(TMZ), the expression level of H19 transcripts was increased compared to wild-type or nonresistant clones, as determined by real-time quantitative reverse transcription polymerase chain reaction. Concomitant treatment with small interfering RNA specifically targeting H19 and TMZ in resistant glioma clones resulted in decreased IC50 values for TMZ, and increased apoptotic rates than control small interfering RNA-treated cells. This was also evident by the increased PARP cleavage in resistant cells exposed to TMZ + si-H19. Furthermore, the reduced expression of H19 altered major drug resistance genes, such as MDR, MRP, and ABCG2, both at the mRNA and protein levels. Taken together, these findings suggest that H19 plays an important role in the development of TMZ resistance, and may represent a novel therapeutic target for TMZ-resistant gliomas. PMID- 27366089 TI - Decreased FOXP3+ and GARP+ Tregs to neoadjuvant chemotherapy associated with favorable prognosis in advanced gastric cancer. AB - Neoadjuvant chemotherapy (NACT) has been an increasingly used therapeutic strategy to improve the outcome of advanced gastric cancer (GC) over the past few decades. Lymphocytic infiltration has been reported to be associated with response to NACT, but the immune cell subpopulation and its prognosis contributing to response in GC have not been clarified yet. In the current study, the tumor infiltration of FOXP3+ and GARP+ regulatory T-cells (Tregs, marked by FOXP3 and GARP) response to NACT in advanced GC and their correlation with prognosis were evaluated. The infiltration of FOXP3+ and GARP+ Tregs in 102 patients with advanced GC who were treated with or without NACT was measured using immunohistochemical method. The infiltration of FOXP3+ and GARP+ Tregs was significantly decreased in the NACT group than in the non-NACT group (P=0.023 and P=0.012, respectively) and significantly associated with tumor, node, metastasis stage (P=0.019 and P=0.011, respectively). There was no significant difference in patient's overall survival between the NACT and non-NACT groups (P=0.166); however, patients in the NACT group with decreased infiltration of FOXP3+ and GARP+ Tregs had longer overall survival (P=0.002 and P<0.001, respectively). Univariate and multivariate analyses indicated that the infiltration of GARP+ Tregs and lymph node metastasis were independent prognostic factors (P=0.038 and P=0.013, respectively). The results demonstrated that NACT could decrease the infiltration of FOXP3+ and GARP+ Tregs, and that the infiltration of GARP+ Tregs may serve as a new prognostic factor of human GC response to NACT. PMID- 27366088 TI - Cigarette smoking and risk of adult glioma: a meta-analysis of 24 observational studies involving more than 2.3 million individuals. AB - BACKGROUND: Cigarette smoking has been shown to be a risk factor for adult glioma by some but not all studies. We conducted a meta-analysis to systematically assess the potential association. METHODS: PubMed and EMBASE were searched from the date of their inception to October 1, 2015, to identify relevant articles. Reference lists from these articles were reviewed to identify additional studies. Both cohort and case-control studies were included. Fixed-effects models were used to calculate the overall relative risk (RR) with corresponding 95% confidence intervals (CIs). RESULTS: The final analysis included 24 studies (seven cohort and 17 case-control studies), involving more than 2.3 million individuals. The combined RR was 1.04 (95% CI: 1.00, 1.09; P=0.073) for ever smokers, 0.97 (95% CI: 0.88, 1.07; P=0.574) for current-smokers, and 1.07 (95% CI: 0.98, 1.16; P=0.130) for past smokers, with little evidence of heterogeneity. Omission of any single study from the analysis had little effect on the result. No evidence of publication bias was found. A small but statistically significant increase was found in past smokers in females (RR: 1.13, 95% CI: 1.00, 1.28; P=0.046) but not in males. CONCLUSION: In general, there was no association between cigarette smoking and adult glioma. The small but statistically significant association in females requires further investigation. PMID- 27366090 TI - MiR-503 inhibits hepatocellular carcinoma cell growth via inhibition of insulin like growth factor 1 receptor. AB - MicroRNAs (miRs) have been demonstrated to play key roles in the development and progression of hepatocellular carcinoma (HCC). However, the regulatory mechanism of miR-503 in HCC has not been fully uncovered. In this study, we found that miR 503 was significantly downregulated in HCC tissues compared to nontumorous liver tissues. Moreover, lower miR-503 levels were associated with the malignant progression of HCC, and the expression of miR-503 was also decreased in several common HCC cell lines compared to normal human liver cell line THLE-3. Overexpression of miR-503 inhibited proliferation but induced apoptosis of LM3 and HepG2 cells. Bioinformatical analysis and luciferase reporter assay further identified insulin-like growth factor 1 receptor (IGF-1R) as a novel target of miR-503 in 293T cells. Moreover, overexpression of miR-503 led to a significant decrease in the protein levels of IGF-1R, while knockdown of miR-503 enhanced its protein levels in LM3 and HepG2 cells. Besides, overexpression of IGF-1R reversed the effects of miR-503-mediated HCC cell proliferation and apoptosis, indicating that IGF-1R acts as a downstream effector of miR-503 in HCC cells. Furthermore, IGF-1R was found to be significantly upregulated in HCC tissues compared to nontumorous liver tissues. In addition, the mRNA levels of IGF-1R were inversely correlated to the miR-503 levels in the HCC tissues. Thus, we demonstrate that miR-503 inhibits the proliferation and induces the apoptosis of HCC cells, partly at least, by directly targeting IGF-1R, and suggest that IGF-1R may serve as a promising target for the treatment of HCC. PMID- 27366091 TI - Intensity-modulated radiotherapy for gliomas:dosimetric effects of changes in gross tumor volume on organs at risk and healthy brain tissue. AB - AIM: The aim of this study was to explore the effects of changes in the gross tumor volume (GTV) on dose distribution in organs at risk (OARs) and healthy brain tissue in patients with gliomas. METHODS: Eleven patients suffering from gliomas with intensity-modulated radiotherapy (IMRT) plans treated with a simultaneous integrated boost technique planned before therapy (initial plans) were prospectively enrolled. At the end of radiotherapy, patients underwent repeat computed tomography and magnetic resonance imaging, and IMRT was replanned. The GTV and dosimetric parameters between the initial and replanned IMRT were compared using the Wilcoxon two-related-sample test, and correlations between the initial GTV and the replanned target volumes were assessed using the bivariate correlation test. RESULTS: The volume of the residual tumor did not change significantly (P>0.05), the volume of the surgical cavity decreased significantly (P<0.05), and the GTV and target volumes decreased significantly at the end of IMRT (all P<0.05). The near-maximum dose to OARs and volumes of healthy brain tissue receiving total doses of 10-50 Gy were lower in the replanned IMRT than in the initial IMRT (all P<0.05). The GTV in the initial plan was significantly positively correlated with the changes in the GTV and planning target volume 1 that occurred during IMRT (all P<0.05). CONCLUSION: The reduction in the GTV in patients with gliomas resulted from shrinkage of the surgical cavity during IMRT, leading to decreased doses to the OARs and healthy brain tissue. Such changes appeared to be most meaningful in patients with large initial GTV values. PMID- 27366092 TI - miR-135a acts as a tumor suppressor in gastric cancer in part by targeting KIFC1. AB - miR-135a was downregulated in the majority of human primary gastric cancer (GC) tissues and GC cell lines. Kinesin family member C1 (KIFC1) was significantly upregulated in GC tissues and cell lines and promoted GC development and progression. We searched for miR-135a targets by using MiRanda, TargetScan, and PicTar tools, and found that KIFC1 was a potential target of miR-135a. Based on these findings, we speculated that miR-135a might target KIFC1 to inhibit GC growth. We determined the expression of miR-135a and KIFC1 by quantitative real time polymerase chain reaction and Western blot assays, respectively, and found downregulation of miR-135a and upregulation of KIFC1 in GC tissues and cell lines. Cell proliferation and apoptosis assays showed that knockdown of KIFC1 inhibited proliferation and promoted apoptosis of GC cells, and miR-135a mimics had similar effects on GC cell proliferation and apoptosis. Furthermore, we verified that KIFC1 was a direct target of miR-135a, which confirmed our speculation that the functional effect of miR-135a on GC cells, at least, in part, depends on KIFC1. These findings suggest that miR-135a has an important role in the suppression of GC and presents a novel mechanism of miRNA-mediated KIFC1 expression in cancer cells. PMID- 27366093 TI - Association between GSTP1 Ile105Val polymorphism and urinary system cancer risk: evidence from 51 studies. AB - The GSTP1 gene plays an important role in detoxification of carcinogens. GSTP1 gene polymorphisms may alter the susceptibility of urinary system cancer. Numerous studies have been performed to investigate the association between GSTP1 Ile105Val (rs1695 A>G) polymorphism and urinary system cancer risk. Nevertheless, the results remain controversial and only prostate cancer and bladder cancer are covered. We identified eligible studies from PubMed, Elsevier, and three equivalent Chinese databases including the Chinese National Knowledge Infrastructure, Wanfang, and Weipu. Pooled odds ratios and 95% confidence intervals were used to assess the strength of the association between GSTP1 Ile105Val polymorphism and urinary system cancer risk. In total, 11,762 cases and 15,150 controls from 51 studies were included in the final meta-analysis. The pooled results from all included studies showed a statistically significant association between GSTP1 Ile105Val polymorphism and urinary system cancer. In the subgroup analyses, the GSTP1 Ile105Val polymorphism was found to be significantly associated with prostate cancer risk and also a risk factor for urinary system cancer among Asians. In conclusion, our meta-analysis indicated that GSTP1 Ile105Val polymorphism was associated with urinary system cancer susceptibility, which needs to be validated by more rigorous data from further large-scale population studies with different ethnicities. PMID- 27366094 TI - 1p/19q codeletion and RET rearrangements in small-cell lung cancer. AB - The prognosis of small-cell lung cancer (SCLC) is poor despite reports suggesting modest improvement in survival. To date, chemotherapy remains the cornerstone treatment for SCLC patients, and many studies have focused on identifying the molecular characteristics of SCLC, which serve as the basis for precision treatments that improve the prognosis of SCLC. For instance, the therapeutic effect of temozolomide, recommended for patients with relapsed SCLC, is linked to 1p/19q codeletion in anaplastic oligodendroglial tumors. A subpopulation of SCLC patients may derive benefit from tyrosine kinase inhibitors targeting RET. In order to identify 1p/19q codeletion and RET rearrangement in SCLC patients, 32 SCLC resected specimens were retrospectively collected between 2008 and 2014 from the Zhejiang Cancer Hospital in People's Republic of China. Fluorescence in situ hybridization was used to detect 1p/19q codeletion and RET rearrangement in the specimens. A 1p single deletion was detected in eight specimens, 19q single deletion was detected in three specimens, and only three specimens had a 1p/19q codeletion. None of the specimens had a RET rearrangement. The three patients whose specimens had a 1p/19q codeletion were alive after 58, 50, and 30 months of follow-up care. There was a trend toward prolonged overall survival for the patients with codeletion compared to no codeletion, 1p single deletion, 19q single deletion, and without 1p and 19q deletion (P=0.113, 0.168, 0.116, and 0.122, respectively). Our data showed that RET rearrangement may be not an ideal molecular target for SCLC therapies in People's Republic of China. Instead, 1p/19q codeletion is a promising marker for a good prognosis and treatment with temozolomide in SCLC. PMID- 27366095 TI - MicroRNA-92a promotes metastasis of nasopharyngeal carcinoma by targeting the PTEN/AKT pathway. AB - MicroRNAs have been confirmed to be a group of important regulators during the pathogenesis of nasopharyngeal carcinoma (NPC). This study confirmed that the expression of microRNA-92a (miR-92a) was significantly upregulated in NPC as compared to noncancerous nasopharyngeal epithelial tissues. Furthermore, high expression of miR-92a was observed in all NPC cell lines, especially in high metastatic cell lines. Clinical analysis indicated that high expression of miR 92a was associated with adverse clinicopathological features including the advanced tumor-node-metastasis stage and distant metastasis, and conferred poor prognosis of patients. In vitro assays showed that miR-92a overexpression potentiated the migration and invasion of 6-10B cells, and miR-92a silencing reduced the number of migrated and invaded 5-8F cells. Phosphatase and tensin homolog (PTEN) was confirmed as a direct downstream target of miR-92a in NPC cells. Otherwise, alteration of miR-92a expression regulated PTEN/AKT pathway in NPC cells. Mechanistically, miR-92a exerted its promoting effects on the metastatic behaviors of NPC cells through suppressing PTEN/AKT pathway. Taken together, this study demonstrates that miR-92a is a promising prognostic biomarker for patients with NPC, and may be a potential therapeutic target to prevent the metastasis of NPC. PMID- 27366096 TI - Bilateral breast adenocarcinomas with EML4-ALK fusion in a patient with multiple metastases successfully treated with crizotinib: is lung the primary site? AB - Breast metastases from non-mammary cancers are rare, especially when they appear synchronously. Clinically, it is vitally important to accurately diagnose these patients, as this will directly influence their treatment and survival. We present a very rare and complex case of bilateral breast adenocarcinomas with an EML4-ALK fusion, which was diagnosed as bilateral breast metastases of non-small cell lung cancer by immunohistochemistry and comprehensive genomic investigation. The patient was successfully treated with an ALK inhibitor (crizotinib); symptoms improved quickly after initiation of crizotinib therapy, and a partial response was observed after 3 months. The experience of diagnosis and treatment of this case indicates the importance and necessity of genomic investigations in such patients, and suggests that we need to consider the rare possibility of this kind of metastasis in order to provide optimal treatment. PMID- 27366097 TI - High expression of substance P and its receptor neurokinin-1 receptor in colorectal cancer is associated with tumor progression and prognosis. AB - BACKGROUND: Epidemiologic evidence suggests that chronic inflammation and/or chronic infection is associated with cancer development, and the inflammatory process may play a crucial role in the carcinogenesis and prognosis of colorectal cancer (CRC). Substance P (SP) belongs to the family of tachykinins and acts as an immunomodulator, binding to the neurokinin-1 receptor (NK1R) to initiate tumor cell proliferation, angiogenesis, and migration, steps that are critical for tumor cell invasion and metastasis. It is suggested that SP/NK1R signaling may play an important role in cancer progression and metastasis. However, the exact involvement and significance of SP and NK1R in CRC pathologies remain to be adequately deciphered. PATIENTS AND METHODS: We performed immunohistochemistry staining on tissue microarrays containing 267 pairs of CRC and adjacent normal tissues to evaluate the clinical significance of SP or NK1R in the progression and prognosis of CRC. We also explored the potential correlation between SP and NK1R in CRC development. RESULTS: Expression levels of SP and NK1R were upregulated in CRC compared with their expressions in adjacent normal tissues (P<0.001). High expression of SP in CRC was significantly associated with lymph node metastasis (P<0.001). We also found that high expression of NK1R in CRC was significantly related to TNM (tumor node metastasis) stage (P=0.010) and lymph node metastasis (P=0.019). A high correlation between SP and NK1R expression was also observed (r=0.419, P<0.001). Survival analysis showed that CRC patients with high expression of SP or NK1R have a poor prognosis when compared to patients with low SP or NK1R expression (log rank test, P<0.05). Multivariate analysis using Cox regression model showed that survival was independently correlated with lymph node metastasis, distant metastasis, and SP expression (P<0.05). CONCLUSION: Upregulation of SP-NK1R may play a crucial role in CRC progression. Moreover, SP-NK1R expression may also be used as a predictor for CRC prognosis. PMID- 27366098 TI - Savings associated with high-dose hypoallergenic house dust mite immunotherapy in rhinitis and/or asthma patients in Spain. AB - OBJECTIVES: To quantify the cost difference between conventional symptomatic treatment of mite allergy and specific subcutaneous immunotherapy (SCIT). METHODS: Observational, retrospective, and multicenter study was carried out in Spain in 2013. The medical records of 419 patients diagnosed with rhinitis and/or bronchial asthma for mite allergy were retrieved. Mean age was 24.9 years (standard deviation 14.4). The use of symptomatic medication (rescue and daily), diagnostic tests, unscheduled medical care, and sick leave days associated with SCIT treatment versus no-SCIT treatment was compared. Also measured was the SCIT treatment to no-SCIT treatment costs ratio: used resources (symptomatic medication, unscheduled medical care, diagnostic tests, and 3 years SCIT treatment and sick leave days) were quantified in euros. Efficacy (decreased resource usage) of first-year treatment was assumed during the remaining 2 years and also during the 3-year follow-up period. RESULTS: After a single year of SCIT, all quantified resources diminished significantly (P<0.05) from baseline. Estimated reduction in cost items included hospital resources (100% in hospitalizations, 82% in visits to the allergist, and 79% in emergency room visits), therapies (56% in rescue medication and 63% in daily medication), diagnostic tests (77%), and sick leave days (94%). Ratio of comparative calculation described as SCIT treatment versus non-SCIT treatment (or conventional symptomatic treatment) is 0.8. CONCLUSION: Direct costs are reduced by 64% and indirect costs by 94%. SCIT of hypoallergenic preparation of dust mite (Acaroid((r))) allows cost savings versus conventional treatment. Estimated savings for the public National Health System are 5.7 times the cost of immunotherapy. PMID- 27366099 TI - Economic analysis of empiric versus diagnostic-driven strategies for immunocompromised patients with suspected fungal infections in the People's Republic of China. AB - Invasive fungal infections (IFIs) require rapid diagnosis and treatment. A decision-analytic model was used to estimate total costs and survival associated with a diagnostic-driven (DD) or an empiric treatment approach in neutropenic patients with hematological malignancies receiving chemotherapy or autologous/allogeneic stem cell transplants in Shanghai, Beijing, Chengdu, and Guangzhou, the People's Republic of China. Treatment initiation for the empiric approach occurred after clinical suspicion of an IFI; treatment initiation for the DD approach occurred after clinical suspicion and a positive IFI diagnostic test result. Model inputs were obtained from the literature; treatment patterns and resource use were based on clinical opinion. Total costs were lower for the DD versus the empiric approach in Shanghai (Y3,232 vs Y4,331), Beijing (Y3,894 vs Y4,864), Chengdu, (Y4,632 vs Y5,795), and Guangzhou (Y8,489 vs Y9,795). Antifungal administration was lower using the DD (5.7%) than empiric (9.8%) approach, with similar survival rates. Results from one-way and probabilistic sensitivity analyses were most sensitive to changes in diagnostic test sensitivity and IFI incidence; the DD approach dominated the empiric approach in 88% of scenarios. These results suggest that a DD compared to an empiric treatment approach in the People's Republic of China may be cost saving, with similar overall survival in immunocompromised patients with suspected IFIs. PMID- 27366100 TI - TNF-related apoptosis-inducing ligand deficiency enhances survival in murine colon ascendens stent peritonitis. AB - BACKGROUND: Apart from inducing apoptosis in tumor cells, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) influences inflammatory reactions. Murine colon ascendens stent peritonitis (CASP) represents a model of diffuse peritonitis. Recently, it has been demonstrated that administration of exogenous TRAIL not only induces apoptosis in neutrophils but also enhances survival in this model. The aim of this study was to examine the impact of genetic TRAIL deficiency on the course of CASP. METHODS: Peritonitis was induced in 6- to 8-week-old female TRAIL (-/-) mice as well as in wild-type mice. The sepsis severity score and survival of mice were monitored. Bacterial loads in blood as well as in the lymphoid organs were examined. Additionally, the number of apoptotic cells within the lymphoid organs was determined. RESULTS: As early as 8 hours postinduction of CASP, TRAIL (-/-) mice were significantly more affected by sepsis than wild-type mice, as measured by the sepsis severity score. However, during the further course of sepsis, TRAIL deficiency led to significantly decreased sepsis severity scores, resulting in an enhanced overall survival in TRAIL (-/-) mice. The better survival of TRAIL (-/-) mice was accompanied by a decreased bacterial load within the blood. In marked contrast, the number of apoptotic cells within the lymphoid organs was highly increased in TRAIL (-/-) mice 20 hours after induction of CASP. CONCLUSION: Hence, exogenous and endogenous TRAIL is protective during the early phase of sepsis, while endogenous TRAIL appears to be detrimental in the later course of this disease. PMID- 27366101 TI - Vitamin D and the immunomodulation of rotator cuff injury. AB - Tendon-to-bone healing after rotator cuff repair surgery has a failure rate of 20%-94%. There has been a recent interest to determine the factors that act as determinants between successful and unsuccessful rotator cuff repair. Vitamin D level in patients is one of the factors that have been linked to bone and muscle proliferation and healing, and it may have an effect on tendon-to-bone healing. The purpose of this article is to critically review relevant published research that relates to the effect of vitamin D on rotator cuff tears and subsequent healing. A review of the literature was conducted to identify all studies that investigate the relationship between vitamin D and tendon healing, in addition to its mechanism of action. The data were then analyzed in order to summarize what is currently known about vitamin D, rotator cuff pathology, and tendon-to-bone healing. The activated metabolite of vitamin D, 1alpha,25-dihydroxyvitamin D3, affects osteoblast proliferation and differentiation. Likewise, vitamin D plays a significant role in the tendon-to-bone healing process by increasing the bone mineral density and strengthening the skeletal muscles. The 1alpha,25 dihydroxyvitamin D3 binds to vitamin D receptors on myocytes to stimulate growth and proliferation. The form of vitamin D produced by the liver, calcifediol, is a key initiator of the myocyte healing process by moving phosphate into myocytes, which improves function and metabolism. Investigation into the effect of vitamin D on tendons has been sparse, but limited studies have been promising. Matrix metalloproteinases play an active role in remodeling the extracellular matrix (ECM) of tendons, particularly deleterious remodeling of the collagen fibers. Also, the levels of transforming growth factor-beta3 positively influence the success of the surgery for rotator cuff repair. In the tendon-to-bone healing process, vitamin D has been shown to successfully influence bone and muscle healing, but more research is needed to delve into the mechanisms of vitamin D as a factor in skeletal tendon health and healing. PMID- 27366102 TI - Role of elosulfase alfa in mucopolysaccharidosis IVA. AB - Mucopolysaccharidosis type IVA (MPS IVA or Morquio A) is an autosomal recessive lysosomal storage disease which results in a striking skeletal phenotype, but does not negatively impact the intellect of the patient. MPS IVA has a phenotypic continuum that ranges from a severe and rapidly progressing form to a slowly progressive form. The clinical diagnosis is often made in the preschool years based on abnormal bone findings on physical examination and dysplasia on radiographic imaging. Supportive care has been the mainstay in caring for patients. Orthopedic physicians often form the core of the care team due to the early and severe skeletal abnormalities; however, systemic disease is common and requires aggressive monitoring and management. Interdisciplinary care teams often consist of medical geneticists, cardiologists, pulmonary specialists, gastroenterologists, otolaryngologists, audiologists, and ophthalmologists. With the US Food and Drug Administration's approval of elosulfase alfa, patients >5 years of age now have access to this medication from the time of diagnosis. The clinical trial with once weekly intravenous dosing (2.0 mg/kg per week) showed improvement in the 6-minute walk test. The composite end point analysis to evaluate the combining changes from baseline in 6-minute walk test, 3-minute stair climb test, and respiratory function showed that at a dose of 2.0 mg/kg per week, subjects performed better when compared to placebo. This indication was clinically meaningful in the treatment group. The treatment was generally well tolerated, and the uncommon infusion reactions responded well to traditional enzyme replacement therapy infusion reaction management algorithms. Currently, clinical trials are underway to determine the efficacy and safety in MPS IVA patients <5 years of age. PMID- 27366103 TI - Pain relief and functional improvement in patients with neuropathic pain associated with spinal cord injury: an exploratory analysis of pregabalin clinical trials. AB - BACKGROUND: Characterizing relationships between pain relief and function can inform patient management decisions. This analysis explored graphically the relationship between pain relief and functional improvement in patients with neuropathic pain associated with spinal cord injury in two clinical trials of pregabalin. METHODS: This was a post hoc analysis of two randomized, double blind, clinical trials in patients who were treated with pregabalin (n=181) or placebo (n=172) for neuropathic pain associated with spinal cord injury. The bivariate relationship between percent pain relief and absolute change in the functional outcomes with placebo and pregabalin was evaluated graphically using scatter plots, and loess curves illustrated the extent of the relationship between pain and function. Linear trend analysis evaluated the statistical significance of these relationships using Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT)-based thresholds of pain reduction (<15%, 15% <30%, 30% to <50%, and >=50%). Outcome measures included modified Brief Pain Inventory pain interference with function in one of the studies and the Medical Outcomes Study Sleep Scale (an 11-point Numeric Rating Scale) and the Hospital Anxiety and Depression Scale (HADS) for the pooled studies. RESULTS: Data ellipses showed a shift with pregabalin relative to placebo toward greater improvement with increasing pain relief for all outcome measures except HADS. Loess curves suggested a relationship between increased pain relief and improved function except for HADS, with the clearest relationship observed for sleep. Linear trend analysis showed significant relationships between pain and Medical Outcomes Study Sleep Scale (P<0.0001) and between pain and function on the modified Brief Pain Inventory Interference Index and most individual items (P<0.05). CONCLUSION: Greater functional improvements were generally achieved at higher levels of clinically significant pain reduction. Pregabalin resulted in shifts from placebo toward greater functional improvement with greater pain relief. PMID- 27366104 TI - Successful treatment of Raynaud's syndrome in a lupus patient with continuous bilateral popliteal sciatic nerve blocks: a case report. AB - Raynaud's syndrome has been treated medically and invasively, sometimes with regional anesthesia leading up to sympathectomy. We demonstrate that regional anesthesia was in this case a useful technique that can allow some patients to find temporary but significant relief from symptoms of Raynaud's syndrome exacerbation. We present a 43-year-old woman with Raynaud's syndrome secondary to lupus who was treated with bilateral popliteal nerve block catheters for ischemic pain and necrosis of her feet; this led to almost immediate resolution of her pain and return of color and function of her feet. While medical management should continue to be a front-line treatment for Raynaud's syndrome, regional anesthesia can be useful in providing rapid dissipation of symptoms and may thus serve as a viable option for short-term management of this syndrome. PMID- 27366105 TI - Effects of group sexual counseling on the traditional perceptions and attitudes of Iranian pregnant women. AB - BACKGROUND: Marital relationships may fluctuate due to physical and psychological changes during pregnancy. This study aimed to investigate the effect of group sexual counseling on the traditional perceptions and attitudes of pregnant women. METHODS: This was a quasiexperimental intervention study. Among the pregnant women who were referred to health care centers in Zahedan, Iran, in 2015 for routine care during pregnancy, 100 individuals were chosen and randomly categorized into two groups: intervention (n=50) and control (n=50). Variables were the participant's attitudes and beliefs on sexual activity during pregnancy. The data were collected during pregnancy using the Sexual Activities and Attitudes Questionnaire. The questionnaire was completed before and 6 weeks after five sessions of group sexual counseling. Data were analyzed using SPSS software (Version 20) with descriptive and analytical statistics. RESULTS: The mean of score changes for sexual attitudes and traditional perceptions in the intervention group was significantly higher than that in the control group (P<0.0001). Analysis of covariance also showed that the mean score of the participant's traditional perceptions and sexual attitudes in both groups was significantly different after the group sexual counseling. DISCUSSION: Due to the positive effect of group sexual counseling on improving the attitudes of pregnant women about sexual issues and reframing the traditional perceptions over sexual activities during pregnancy, it is recommended that this educational intervention should be integrated into counseling and prenatal care for pregnant women. PMID- 27366106 TI - Can theoretical intervention improve hand hygiene behavior among nurses? AB - BACKGROUND: Hand washing is the best strategy to prevent known nosocomial infections but the nurses' hand hygiene is estimated to be poor in Iran. OBJECTIVE: This study aimed to determine the effectiveness of BASNEF (Behavior, Attitude, Subjective Norms, and Enabling Factors) model on hand hygiene adherence education. METHODS: This controlled quasi-experimental study was conducted on 70 hemodialysis unit nurses (35 case and 35 control) in the health and educational centers of the University of Medical Sciences of Urmia, Iran. To collect the data, a six-part validated and reliable questionnaire was used. The data were analyzed using SPSS version18, using Wilcoxon, Mann-Whitney, chi-square, and Fisher's exact tests. The significance level was considered P<0.05. RESULTS: The mean age was 38.4+/-8.1 years for the intervention group and 40.2+/-8.0 years for the control group. There was no significant difference between the two groups for any demographic variables. Also, before the intervention, there was no significant difference between the two groups for any components of the BASNEF model. Post-intervention, the attitude, subjective norms, enabling factors, and intention improved significantly in the intervention group (P<0.001), but hand hygiene behavior did not show any significant change in the intervention group (P=0.16). CONCLUSION: Despite the improving attitudes and intention, the intervention had no significant effect on hand hygiene behavior among the studied nurses. PMID- 27366107 TI - Longitudinal burnout-collaboration patterns in Japanese medical care workers at special needs schools: a latent class growth analysis. AB - The present study aimed to identify and characterize potential burnout types and the relationship between burnout and collaboration over time. Latent class growth analysis and the growth mixture model were used to identify and characterize heterogeneous patterns of longitudinal stability and change in burnout, and the relationship between burnout and collaboration. We collected longitudinal data at three time points based on Japanese academic terms. The 396 study participants included academic teachers, yogo teachers, and registered nurses in Japanese special needs schools. The best model included four types of both burnout and collaboration in latent class growth analysis with intercept, slope, and quadratic terms. The four types of burnout were as follows: low stable, moderate unstable, high unstable, and high decreasing. They were identified as involving inverse collaboration function. The results indicated that there could be dynamic burnout types, namely moderate unstable, high unstable, and high decreasing, when focusing on growth trajectories in latent class analyses. The finding that collaboration was dynamic for dynamic burnout types and stable for stable burnout types is of great interest. This was probably related to the inverse relationship between the two constructs. PMID- 27366108 TI - Validation of the Oxford Participation and Activities Questionnaire. AB - PURPOSE: There is growing interest in the management of long-term conditions and in keeping people active and participating in the community. Testing the effectiveness of interventions that aim to affect activities and participation can be challenging without a well-developed, valid, and reliable instrument. This study therefore aims to develop a patient-reported outcome measure, the Oxford Participation and Activities Questionnaire (Ox-PAQ), which is theoretically grounded in the World Health Organization's International Classification of Functioning, Disability, and Health (ICF) and fully compliant with current best practice guidelines. METHODS: Questionnaire items generated from patient interviews and based on the nine chapters of the ICF were administered by postal survey to 386 people with three neurological conditions: motor neuron disease, multiple sclerosis, and Parkinson's disease. Participants also completed the Medical Outcomes Study (MOS) 36-Item Short Form Health Survey (SF-36) and EQ-5D 5L. RESULTS: Thus, 334 participants completed the survey, a response rate of 86.5%. Factor analysis techniques identified three Ox-PAQ domains, consisting of 23 items, accounting for 72.8% of variance. Internal reliability for the three domains was high (Cronbach's alpha: 0.81-0.96), as was test-retest reliability (intraclass correlation: 0.83-0.92). Concurrent validity was demonstrated through highly significant relationships with relevant domains of the MOS SF-36 and the EQ- 5D-5L. Assessment of known-groups validity identified significant differences in Ox-PAQ scores among the three conditions included in the survey. CONCLUSION: Results suggest that the Ox-PAQ is a valid and reliable measure of participation and activity. The measure will now be validated in a range of further conditions, and additional properties, such as responsiveness, will also be assessed in the next phase of the instrument's development. PMID- 27366110 TI - Curious afterlives: the enduring appeal of the criminal corpse. AB - Not only did the criminal corpse have actual medicinal and magical power for Europeans, it also had social and cultural meaning as an object, a curio or secular relic. This paper considers the appeal of notorious bodies. From books bound in the skin of a criminal, to preserved and exhibited heads, from fragments of the hangman's rope to the exhibition of the skeleton, the story of the afterlife of criminal bodies and the material culture most immediately associated with them begins with the collection and exchange of bodies and moves into contemporary preoccupations with authenticity. This paper considers the bodies of three notorious criminals of the eighteenth century: Eugene Aram, William Burke and William Corder. It ends with some reflections on the glamour of the authentic body of a notorious or celebrated individual - using the response to the discovery of the body of Richard III as an example. PMID- 27366109 TI - Opioid-induced constipation: rationale for the role of norbuprenorphine in buprenorphine-treated individuals. AB - Buprenorphine and buprenorphine-naloxone fixed combinations are effective for managing patients with opioid dependence, but constipation is one of the most common side effects. Evidence indicates that the rate of constipation is lower when patients are switched from sublingual buprenorphine-naloxone tablets or films to a bilayered bioerodible mucoadhesive buccal film formulation, and while the bilayered buccal film promotes unidirectional drug flow across the buccal mucosa, the mechanism for the reduced constipation is unclear. Pharmacokinetic simulations indicate that chronic dosing of sublingually administered buprenorphine may expose patients to higher concentrations of norbuprenorphine than buprenorphine, while chronic dosing of the buccal formulation results in higher buprenorphine concentrations than norbuprenorphine. Because norbuprenorphine is a potent full agonist at mu-opioid receptors, the differences in norbuprenorphine exposure may explain the observed differences in treatment emergent constipation between the sublingual formulation and the buccal film formulation of buprenorphine-naloxone. To facilitate the understanding and management of opioid-dependent patients at risk of developing opioid-induced constipation, the clinical profiles of these formulations of buprenorphine and buprenorphine-naloxone are summarized, and the incidence of treatment-emergent constipation in clinical trials is reviewed. These data are used to propose a potential role for exposure to norbuprenorphine, an active metabolite of buprenorphine, in the pathophysiology of opioid-induced constipation. PMID- 27366111 TI - The experience of meaning in circle dance. AB - Circle dance, which derives from the tradition of folk dances, is practised worldwide. This article explores the meanings participants attribute to it. In depth interviews with 39 participants, teachers and coordinators of teacher training programmes from the circle dance network in the United Kingdom were undertaken. Applying a constructivist grounded theory approach, major categories, representing respectively the experiences of circle dance participants, teachers and coordinators, were developed. This article specifically focuses on the first major category, termed "I can't imagine life without it", which relates to the experience of 22 dancers. From an occupational perspective, the study reveals how participants realise a sense of meaning and satisfaction through engagement in circle dance and the potential contribution of this occupation to well-being. PMID- 27366112 TI - Diabetes knowledge in nursing homes and home-based care services: a validation study of the Michigan Diabetes Knowledge Test adapted for use among nursing personnel. AB - BACKGROUND: Providing high-quality diabetes care in nursing homes and home-based care facilities requires suitable instruments to evaluate the level of diabetes knowledge among the health-care providers. Thus, the aim of this study was to examine the psychometric properties of the Michigan Diabetes Knowledge Test adapted for use among nursing personnel. METHODS: The study included 127 nursing personnel (32 registered nurses, 69 nursing aides and 26 nursing assistants) at three nursing homes and one home-based care facility in Norway. We examined the reliability and content and construct validity of the Michigan Diabetes Knowledge Test. RESULTS: The items in both the general diabetes subscale and the insulin use subscale were considered relevant and appropriate. The instrument showed satisfactory properties for distinguishing between groups. Item response theory based measurements and item information curves indicate maximum information at average or lower knowledge scores. Internal consistency and the item-total correlations were quite weak, indicating that the Michigan Diabetes Knowledge Test measures a set of items related to various relevant knowledge topics but not necessarily related to each other. CONCLUSIONS: The Michigan Diabetes Knowledge Test measures a broad range of topics relevant to diabetes care. It is an appropriate instrument for identifying individual and distinct needs for diabetes education among nursing personnel. The knowledge gaps identified by the Michigan Diabetes Knowledge Test could also provide useful input for the content of educational activities. However, some revision of the test should be considered. PMID- 27366113 TI - A microalga, Euglena tuba induces apoptosis and suppresses metastasis in human lung and breast carcinoma cells through ROS-mediated regulation of MAPKs. AB - BACKGROUND: Euglena tuba, a microalga, is known for its excellent antioxidant and iron-chelation activities; however its anticancer efficacies have not been reported yet. This study investigates the antitumor and antimetastatic activities of 70 % methanolic extract of Euglena tuba (ETME) against human lung (A549) and breast cancer (MCF-7) cells in vitro. Moreover, we had examined ETME's role in inducing intracellular ROS with the regulation of antioxidants and MAPK pathway. METHODS: Anticancer activity of ETME was thoroughly studied using flow cytometry, confocal microscopy and western blotting; along with various biochemical assays for analysing ROS-induced regulation of antioxidant enzymes. Inhibition of invasion and migration of malignant cells by ETME were investigated by wound healing and zymographic studies. DNA-Protein interaction with ETME was also studied. RESULTS: ETME inhibited the growth of both A549 (IC50 92.14 ug/ml) and MCF-7 cells (IC50 50.27 ug/ml) by inducing apoptosis, while remained non-toxic against nomral WI-38 cells (IC50 911.43 ug/ml). ETME treatment resulted in increasing Bax/Bcl-2 ratio, BID truncation and activation of caspase cascade. This ultimately leads to PARP degradation and apoptosis through the intrinsic and extrinsic pathway in both A549 and MCF-7 cells. Wound healing and gelatin zymography studies revealed that ETME significantly inhibited the invasion and migration of both A549 and MCF-7 cells dose-dependently through the downregulation of MMP-9. Further investigations showed that ETME selectively induces intracellular ROS, regulated the levels of intracellular antioxidants and suppresses the activation of ERK1/2, JNK, P38 mitogen-activated protein kinase pathways in both type of malignant cells. Further DNA and protein binding studies revealed that ETME strongly interact with DNA as well as protein attributing the possibilities of presence of components which are targeting the macromolecules in cancer cells. Moreover, when the identified compounds from ETME were examined for their cytotoxicities individually, it was found that they lost their specificities towards cancer cells and also attacked normal cells. CONCLUSIONS: Our study suggests that ETME retards the growth of both lung and breast cancer cells, in vitro, through multivariate mechanisms, proving its candidature for the development of better and safer drugs against these cancers. PMID- 27366114 TI - Laparoscopic spleen-preserving hilar lymph node dissection through pre-pancreatic and retro-pancreatic approach in patients with gastric cancer. AB - BACKGROUND: The conventional radical resection of proximal gastric cancer is even more risky when performed laparoscopically, though this technique is widely used in gastrointestinal surgery and is accepted as the superior method. This paper explores the feasibility of laparoscopic spleen-preserving hilar lymph node dissection using a retro-pancreatic approach for the treatment of proximal gastric cancer. METHODS: Two cadavers were dissected for examination of and the pre-pancreatic and retro-pancreatic spaces. Following the dissection of the cadavers, ten live patients with proximal gastric cancer from May 2008 to May 2013 at Nanfang Hospital, Guangzhou, China, were given total gastrectomy and adjuvant splenic hilar lymph node clearance through pre-pancreatic and retro pancreatic approach on the precondition of preserving the pancreas and spleen. The clinicopathologic characteristics, as well as the intraoperative and postoperative variables affecting the procedure, were observed and analyzed. RESULTS: Anatomy of the space anterior and posterior to the pancreas in the two cadavers demonstrated the feasibility of pre-pancreatic and retro-pancreatic approach. The surgeries were all successfully performed laparoscopically; conversion to laparotomy was not necessary for any of the ten patients. The overall mean operative time was 243.6 +/- 45 min. The mean estimated blood loss was 232 +/- 80 ml. At the time of follow-up (median 12 months post-surgery), there had been neither local recurrence nor mortality in any of the patients. CONCLUSION: Laparoscopic spleen- and pancreas-preserving splenic hilar lymph node dissection during total gastrectomy, using both pre-pancreatic and retro pancreatic approaches, is indicated as a safe and feasible method for the treatment of proximal gastric cancer. PMID- 27366115 TI - Who are the Gatekeepers? Predictors of Maternal Gatekeeping. AB - OBJECTIVE: The goal of this study was to identify determinants of maternal gatekeeping at the transition to parenthood. DESIGN: Participants included 182 different-gender dual-earner couples. During pregnancy, expectant parents completed questionnaires regarding their psychological functioning, attitudes, and expectations, and at 3 months postpartum questionnaires regarding maternal gatekeeping behavior and gate closing attitudes. RESULTS: SEM analyses revealed that mothers were more likely to close the gate to fathers when mothers held greater perfectionistic expectations for fathers' parenting, had poorer psychological functioning, perceived their romantic relationship as less stable, and had higher levels of parenting self-efficacy. In contrast, fathers with lower parenting self-efficacy appeared to elicit greater maternal gate closing behavior. Mothers who engaged in greater gate opening behavior were more religious. CONCLUSIONS: Maternal gatekeeping may be more strongly associated with maternal expectations and psychological functioning than with maternal traditional gender attitudes. Fathers' characteristics are less predictive of maternal gatekeeping than mothers' characteristics. PMID- 27366117 TI - Take us to the beach. PMID- 27366116 TI - Longitudinal Associations Between Substance Use and Violence in Adolescence Through Adulthood. AB - Substance use and violence are interrelated behaviors during adolescence and early adulthood. Using National Longitudinal Study of Adolescent to Adult Health data, this study examined the longitudinal relationships between (a) alcohol and violence perpetration, (b) marijuana and perpetration, (c) alcohol and victimization, and (d) marijuana and victimization. Cross-lagged structural equation models showed that longitudinal patterns of violence and substance use vary somewhat and that the ways preceding stages of violence and substance use are associated with subsequent violence, and substance use differ by violence, substance type, and transitional stage. Our findings call for primary and secondary prevention strategies targeting early adulthood. PMID- 27366118 TI - Teresa L. Knott, AHIP, Medical Library Association President, 2016-2017. PMID- 27366119 TI - Resource format preferences across the medical curriculum. AB - OBJECTIVE: This research study sought to determine the formats (print or electronic) of articles and book chapters most-preferred by first-year medical students, third-year medical students entering clinical clerkships, and incoming residents and to determine if these preferences change during the course of the medical curriculum. These trends will enable academic health sciences libraries to make appropriate collection development decisions to best cater to their user populations. METHODS: First-year medical students, third-year medical students, and incoming medical residents were asked to complete a paper survey from September 2014 to June 2015. The survey consisted of five multiple-choice questions, with two questions given space for optional short answers. Quantitative and qualitative responses were collected and calculated using Microsoft Excel. RESULTS: First-year students, third-year students, and incoming residents all preferred to read journal articles and book chapters in print, except in cases where the article or book chapter is under ten pages in length. Although print is preferred, demand for electronic articles and book chapters increases as students progress from undergraduate medical education into residency. The only category where a majority of incoming residents chose an electronic resource was which format they would give to a colleague, if the article or book chapter was critical to the care of an individual patient. CONCLUSIONS: The preference for print resources is strong across the medical curriculum, although residents show an increased preference for electronic materials when compared to first- and third-year students. Academic health sciences libraries should take these preferences into account when making decisions regarding collection development. PMID- 27366120 TI - Instructional methods used by health sciences librarians to teach evidence-based practice (EBP): a systematic review. AB - BACKGROUND: Librarians often teach evidence-based practice (EBP) within health sciences curricula. It is not known what teaching methods are most effective. METHODS: A systematic review of the literature was conducted searching CINAHL, EMBASE, ERIC, LISTA, PubMed, Scopus, and others. Searches were completed through December 2014. No limits were applied. Hand searching of Medical Library Association annual meeting abstracts from 2009-2014 was also completed. Studies must be about EBP instruction by a librarian within undergraduate or graduate health sciences curricula and include skills assessment. Studies with no assessment, letters and comments, and veterinary education studies were excluded. Data extraction and critical appraisal were performed to determine the risk of bias of each study. RESULTS: Twenty-seven studies were included for analysis. Studies occurred in the United States (20), Canada (3), the United Kingdom (1), and Italy (1), with 22 in medicine and 5 in allied health. Teaching methods included lecture (20), small group or one-on-one instruction (16), computer lab practice (15), and online learning (6). Assessments were quizzes or tests, pretests and posttests, peer-review, search strategy evaluations, clinical scenario assignments, or a hybrid. Due to large variability across studies, meta analysis was not conducted. DISCUSSION: Findings were weakly significant for positive change in search performance for most studies. Only one study compared teaching methods, and no one teaching method proved more effective. Future studies could conduct multisite interventions using randomized or quasi randomized controlled trial study design and standardized assessment tools to measure outcomes. PMID- 27366121 TI - Norming a VALUE rubric to assess graduate information literacy skills. AB - OBJECTIVE: The study evaluated whether a modified version of the information literacy Valid Assessment of Learning in Undergraduate Education (VALUE) rubric would be useful for assessing the information literacy skills of graduate health sciences students. METHODS: Through facilitated calibration workshops, an interdepartmental six-person team of librarians and faculty engaged in guided discussion about the meaning of the rubric criteria. They applied the rubric to score student work for a peer-review essay assignment in the "Information Literacy for Evidence-Based Practice" course. To determine inter-rater reliability, the raters participated in a follow-up exercise in which they independently applied the rubric to ten samples of work from a research project in the doctor of physical therapy program: the patient case report assignment. RESULTS: For the peer-review essay, a high level of consistency in scoring was achieved for the second workshop, with statistically significant intra-class correlation coefficients above 0.8 for 3 criteria: "Determine the extent of evidence needed," "Use evidence effectively to accomplish a specific purpose," and "Access the needed evidence." Participants concurred that the essay prompt and rubric criteria adequately discriminated the quality of student work for the peer-review essay assignment. When raters independently scored the patient case report assignment, inter-rater agreement was low and statistically insignificant for all rubric criteria (kappa=-0.16, p>0.05-kappa=0.12, p>0.05). CONCLUSIONS: While the peer-review essay assignment lent itself well to rubric calibration, scorers had a difficult time with the patient case report. Lack of familiarity among some raters with the specifics of the patient case report assignment and subject matter might have accounted for low inter-rater reliability. When norming, it is important to hold conversations about search strategies and expectations of performance. Overall, the authors found the rubric to be appropriate for assessing information literacy skills of graduate health sciences students. PMID- 27366122 TI - How do early career health sciences information professionals gain competencies? AB - OBJECTIVE: The purpose of this study was to describe early career health sciences information professionals' self-reported attainment of the Medical Library Association (MLA) Competencies for Lifelong Learning and Professional Success and to investigate the various methods by which participants developed these competencies. METHODS: A SurveyMonkey survey was designed to ascertain participants' demographic information and their competency attainment. "Early career" health information professionals were defined as those with less than five years of professional experience. Participants were asked to rate each of the seven competencies on a five-point Likert scale regarding their level of agreement with the statement, "I have demonstrated this competency." Participants who responded positively were then asked to indicate how they acquired the competency on a multiple-choice, multiple-answer list. Free-text fields were provided for general comments and for participants to elaborate on their answers. The survey was distributed through the MLA email discussion list and other related email discussion lists. Participation was anonymous. RESULTS: One hundred eighty-seven responses were received. Out of those 187 respondents, 95 completed the entire survey. The majority of early career health sciences information professionals agreed that they had attained all 7 competencies. Of the various methods used to develop competencies, the most selected method was formal library and information studies education. Participants were least likely to report attaining competencies via mentoring, volunteering, or internships. Participants reported the highest level of confidence in having attained the "Health Sciences Information Services" competency, and the lowest level of confidence in having attained the "Research, Analysis, and Interpretation" competency. CONCLUSIONS: These results contribute to the ongoing discussions regarding proposed changes to the MLA competencies. The results may also inform the development of educational and professional development opportunities for prospective or early career health information professionals. PMID- 27366123 TI - Effectiveness of adverse effects search filters: drugs versus medical devices. AB - OBJECTIVE: The study tested the performance of adverse effects search filters when searching for safety information on medical devices, procedures, and diagnostic tests in MEDLINE and Embase. METHODS: The sensitivity of 3 filters was determined using a sample of 631 references from 131 rapid reviews related to the safety of health technologies. The references were divided into 2 sets by type of intervention: drugs and nondrug health technologies. Keyword and indexing analysis were performed on references from the nondrug testing set that 1 or more of the filters did not retrieve. RESULTS: For all 3 filters, sensitivity was lower for nondrug health technologies (ranging from 53%-87%) than for drugs (88% 93%) in both databases. When tested on the nondrug health technologies set, sensitivity was lower in Embase (ranging from 53%-81%) than in MEDLINE (67%-87%) for all filters. Of the nondrug records that 1 or more of the filters missed, 39% of the missed MEDLINE records and 18% of the missed Embase records did not contain any indexing terms related to adverse events. Analyzing the titles and abstracts of nondrug records that were missed by any 1 filter, the most commonly used keywords related to adverse effects were: risk, complications, mortality, contamination, hemorrhage, and failure. CONCLUSIONS: In this study, adverse effects filters were less effective at finding information about the safety of medical devices, procedures, and tests compared to information about the safety of drugs. PMID- 27366124 TI - Patron perception and utilization of an embedded librarian program. AB - OBJECTIVE: The study measured the perceived value of an academic library's embedded librarian service model. SETTING: The study took place at the health sciences campuses of a research institution. METHODS: A web-based survey was distributed that asked respondents a series of questions about their utilization of and satisfaction with embedded librarians and services. RESULTS: Over 58% of respondents reported being aware of their embedded librarians, and 95% of these were satisfied with provided services. CONCLUSIONS: The overall satisfaction with services was encouraging, but awareness of the embedded program was low, suggesting an overall need for marketing of services. PMID- 27366125 TI - Librarians help high school students improve research skills. PMID- 27366126 TI - Virtual embedded librarianship program: a personal view. PMID- 27366127 TI - What's new in abstracts of science articles. PMID- 27366128 TI - Health sciences librarians off the radar. PMID- 27366129 TI - An elemental strategy. PMID- 27366130 TI - De-duplication of database search results for systematic reviews in EndNote. PMID- 27366131 TI - Corrections. AB - [This corrects the article on p. 3 in vol. 104, PMID: 26807047.]. PMID- 27366132 TI - Effects of thirty and sixty minutes of moderate-intensity aerobic exercise on postprandial lipemia and inflammation in overweight men: a randomized cross-over study. AB - BACKGROUND: The transient rise in blood lipids following a high-fat meal (HFM), known as postprandial lipemia, is linked to systemic inflammation and cardiovascular disease, but can be blunted by exercise. However, minimal research has investigated the effects of realistic exercise bouts on postprandial lipemia and inflammation in at-risk individuals. The purpose of this study was to assess the effects of moderate-intensity aerobic exercise lasting 30 or 60 min performed the evening before a HFM, on postprandial lipemia and inflammation in overweight, insufficiently active men. METHODS: In this randomized-crossover study, twelve participants remained sedentary (CON), or performed a brisk walk on a treadmill at 60 % VO2peak for either 30 min (EX-30) or 60 min (EX-60), after which they consumed a small snack (270 kcal) to partially replace exercise energy expenditure. Following a 12-h overnight fast, participants consumed a standard HFM (1 g fat/kg; 1 g CHO/kg; 1117.8 +/- 117.0 kcal). Blood draws were performed at baseline (pre-HFM) and 1, 2, 4, 6, and 8 h post-HFM to assess glucose, insulin, lipids, and systemic inflammation. RESULTS: There were no significant differences (p > 0.05) in fasting triglycerides between EX-60 (118.7 +/- 68.3 mg/dL), CON (134.8 +/- 66.2 mg/dL) or EX-30 (135.5 +/- 85.4 mg/dL). There were no differences in peak, time-to-peak, total or incremental area-under-the-curve between trials for triglyceride response (p > 0.05). There was no significant main effect of time (p > 0.05) in IL-1ra, IL-4, IL-5, IL-6, IL-10 or TNF-alpha from baseline to 8 h post-HFM in any trial. CONCLUSIONS: In summary, we found that in overweight, insufficiently active men, neither 30 nor 60 min of moderate intensity exercise performed 12 h prior to a HFM attenuated postprandial lipemia or inflammation, which could potentially be explained by the partial caloric replacement of exercise energy expenditure. PMID- 27366133 TI - Protective effect of crocin against reperfusion-induced cardiac arrhythmias in anaesthetized rats. AB - The aim of the present study was to investigate the effects of crocin - a natural antioxidant derived from saffron - on cardiac reperfusion-induced arrhythmia and antioxidant systems such as catalase and superoxide dismutase (SOD) enzyme activities, glutathione (GSH) and malondialdehyde (MDA, as a marker of lipid peroxidation) levels. Rats in 4 experimental groups were administered crocin (20 mg/kg/day) or vehicle (i.p.) for 21 days with or without cardiac ischemia reperfusion (IR). At the end of this period, hearts of anaesthetized animals in IR and "Cr + IR" groups were subjected to 10 min occlusion of the left anterior descending coronary artery and thereafter reperfused for 30 min. The results suggest that crocin is partially capable of suppressing reperfusion-induced arrhythmias. Compared to control group, ischemic-reperfusion injury significantly decreased SOD activity and GSH level and increased MDA level of heart muscle. "Cr + IR" group showed remarkably increased catalase activity in heart tissue (28.7 +/- 6.6 vs. 23.6 +/- 4.1 U/mg protein, P < 0.05) compared to the IR group. The level of cardiac tissue SOD activity in the "Cr + IR" group animals did not decline significantly compared to rats that were administered crocin alone with no ischemia. The results suggest a protective role of crocin on cardiac reperfusion arrhythmias which may at least partially be related to stability or even amplification of antioxidant systems. Crocin may potentially be useful for treatment or prevention of arrhythmias in patients with ischemic heart disease and this issue remains to be investigated in future clinical studies. PMID- 27366135 TI - Effect of cranberry dietary supplements with different brands on human CYP3A4 enzyme. AB - The use of dietary supplements has increased dramatically, making drug interactions with those supplements a major concern. Because dietary supplements are not subject to the same regulations as prescription drugs, we hypothesize that the content of their active ingredients may vary among manufacturers, potentially causing a large variation in therapeutic outcome. The current study aimed to test this hypothesis on commonly used cranberry dietary supplements. Activity of human CYP3A4 enzyme was used as a parameter to determine the effect of cranberry supplement from nine manufacturers. The content of a cranberry product, equivalent to one capsule, was extracted with methanol. Aliquots of the extract were tested for their ability to inhibit the metabolism of the human CYP3A4 substrate quinine, using an in vitro liver microsomal technique. Human liver microsomes and quinine were incubated with or without (i.e. as control) cranberry extract. Formation of quinine's metabolite 3-hydroxyquinine, generated by the CYP3A4-mediated reaction was measured by a HPLC method. Of nine cranberry products tested, eight products had little or no effect but only one brand (Nature's Herbs 600 mg) caused very strong inhibition (67.2 %) of CYP3A4. The reason for this inhibition is unknown. The effect of cranberry was varied and ranged from 4.4 % activation by Ride Aid 800 mg to 67.2 % inhibition by Nature's Herbs 600 mg. Lack of effect on human CYP3A4 activity suggests that use of cranberry dietary supplement is unlikely to cause significant interactions with drugs metabolized by CYP3A4. PMID- 27366134 TI - Effects of Cannabis sativa extract on haloperidol-induced catalepsy and oxidative stress in the mice. AB - Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal symptoms due to blockade of dopamine D2 receptors in the striatum. Interest in medicinal uses of cannabis is growing. Cannabis sativa has been suggested as a possible adjunctive in treatment of Parkinson's disease. The present study aimed to investigate the effect of repeated administration of an extract of Cannabis sativa on catalepsy and brain oxidative stress induced by haloperidol administration in mice. Cannabis extract was given by subcutaneous route at 5, 10 or 20 mg/kg (expressed as Delta(9)-tetrahydrocannabinol) once daily for 18 days and the effect on haloperidol (1 mg/kg, i.p.)-induced catalepsy was examined at selected time intervals using the bar test. Mice were euthanized 18 days after starting cannabis injection when biochemical assays were carried out. Malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (the concentrations of nitrite/nitrate) were determined in brain and liver. In saline treated mice, no catalepsy was observed at doses of cannabis up to 20 mg/kg. Mice treated with haloperidol at the dose of 1 mg/kg, exhibited significant cataleptic response. Mice treated with cannabis and haloperidol showed significant decrease in catalepsy duration, compared with the haloperidol only treated group. This decrease in catalepsy duration was evident on days 1-12 after starting cannabis injection. Later the effect of cannabis was not apparent. The administration of only cannabis (10 or 20 mg/kg) decreased brain MDA by 17.5 and 21.8 %, respectively. The level of nitric oxide decreased by 18 % after cannabis at 20 mg/kg. Glucose in brain decreased by 20.1 % after 20 mg/kg of cannabis extract. The administration of only haloperidol increased MDA (22.2 %), decreased GSH (25.7 %) and increased brain nitric oxide by 44.1 %. The administration of cannabis (10 or 20 mg/kg) to haloperidol-treated mice resulted in a significant decrease in brain MDA and nitric oxide as well as a significant increase in GSH and glucose compared with the haloperidol-control group. Cannabis had no significant effects on liver MDA, GSH, nitric oxide in saline or haloperidol treated mice. It is concluded that cannabis improves catalepsy induced by haloperidol though the effect is not maintained on repeated cannabis administration. Cannabis alters the oxidative status of the brain in favor of reducing lipid peroxidation, but reduces brain glucose, which would impair brain energetics. PMID- 27366136 TI - Blood pressure profile in continuous ambulatory peritoneal dialysis patients. AB - BACKGROUND: Cardiovascular mortality is the leading cause of death in end stage renal disease. Despite being on continuous ambulatory peritoneal dialysis (CAPD), blood pressure (BP) remains poorly controlled. A higher pulse pressure and non dipping are associated with increased cardiovascular mortality. We studied BP control and the prevalence of non dipping in CAPD patients. METHODS: All patients undergoing CAPD at our institution who met the inclusion criteria were recruited. We compared BP control and dipping status in diabetic and non diabetic patients on CAPD. We also determined whether BP and peritoneal membrane permeability were associated. RESULTS: Forty six patients with a mean age 45 +/- 13 years were enrolled. Diabetic patients were older (mean age 54 +/- 13 vs. 40 +/- 11 yrs, p <0.001), had a lower mean diastolic BP (80 +/- 14 vs. 90 +/- 14 mmHg, p = 0.025) and a higher mean pulse pressure (59 +/- 17 vs. 49 +/- 14 mmHg, p = 0.035). They were also non dippers (n = 15 vs. n = 1, p = 0.007). The low and low average transporters tended to have a higher systolic BP (p = 0.054) and a higher pulse pressure (p = 0.058). On multivariate analysis, age was the main predictor of pulse pressure. CONCLUSION: Despite being on chronic maintenance PD, BP was not well controlled. Diabetic patients had a higher pulse pressure and were non dippers thereby increasing their cardiovascular risk. We should therefore optimize BP control and aim to restore the nocturnal dip in these patients. PMID- 27366137 TI - The anti-infarct, antistunning and antiarrhythmic effects of oleuropein in isolated rat heart. AB - Previous studies have reported that oleuropein, the major constituent of olive leaves, has cardioprotective effects. There is no report related to oleuropein and ischemic-reperfusion injuries (cardiac dysfunction and myocardial infarction) as well as preconditioning in rat hearts. 56 male Wistar rats were divided into 7 groups (n=8). Group 1 as the control group and groups 2 to 7 as the treatment groups that received a single dose of oleuropein (100 mg/kg, i.p.) 1, 3, 6, 12, 24 and 48 hours before the excision of the heart, respectively. After these times, their hearts were excised and subjected to 30 min regional ischemia and 120 min reperfusion under Langendorff apparatus. Electrocardiogram and intraventricular pressures were monitored and recorded throughout the procedure. Finally, infarct size was measured by triphenyltetrazolium chloride staining. Compared to the control group, oleuropein significantly reduced infarct size and reperfusion-induced cardiac dysfunction in groups 2 and 3. Oleuropein markedly attenuated both ischemic and reperfusion arrhythmias in groups 2 and 3. There was no significant difference between other groups (4 to 7) than the control group. Heart rate had no significant difference among all of the groups. These results indicate that pretreatment of rats with a single dose of intraperitoneal oleuropein could protect their heart against ischemic-reperfusion injury for at least 3 hours. However, it has no preconditioning effect, since oleuropein had not cardioprotective effects 24 hour later. PMID- 27366138 TI - Toxicity evaluation of crankcase oil in rats. AB - The aim of this study was to investigate the effect of crankcase oil on the cellular and functional integrity of rat skin. Thirty (30) rats were randomly grouped into six viz groups A-F. Group A (base-line control) received 2 ml of distilled water. 2.5 %, 5.0 %, 7.5 %, and 10.0 % v/v of the crankcase oil were prepared using unused oil as solvent and 2 ml of the concentrations were topically administered to groups C-F respectively for seven consecutive days. Group B served as positive control and received 2 ml of the unused oil. The rats were sacrificed 24 hours after the last administration, and blood and part of the skin were collected. Alkaline phosphatase (ALP), acid phosphatase (ACP), superoxide dismutase (SOD) and malondialdehyde level in the blood and skin samples collected were evaluated. Elemental analysis of the crankcase oil was also carried out. The result revealed high lead, iron and chromium levels. Blood lead concentration of rats was significantly (P<0.05) high after seven days of administration. ALP level in skin and serum increased significantly (P<0.05) with the concentration of crankcase oil. There was a significant decrease (P<0.05) in skin ACP activity while it increased significantly (P<0.05) in the serum. Similar results were observed in the SOD levels of the serum and the skin. The level increased significantly (P<0.05) in groups D-F when compared with controls. The MDA concentration of both serum and skin were significantly (P<0.05) elevated. This suggests toxic potential of used lubricating oil and its potential predisposition to cancer. PMID- 27366139 TI - Protective effect of curcumin on experimentally induced arthritic rats: detailed histopathological study of the joints and white blood cell count. AB - Curcuma longa (turmeric) rhizomes contains curcumin, an active compound which possesses anti-inflammatory effects. Collagen-induced arthritis (CIA) is an accepted experimental animal model of rheumatoid arthritis. The present study aimed to observe the histological changes in the joints of experimental arthritic rats treated with curcumin. Twenty four male Sprague-Dawley (approximately 7 weeks-old) rats were randomly divided into four groups. Three groups were immunized with 150 ug collagen. All rats with established CIA, with arthritis scores exceeding 1, were orally treated with betamethasone (0.5 mg/ml/kg body weight), curcumin (110 mg/ml/kg body weight) or olive oil (1.0 ml/kg body weight) daily, for two weeks. One remaining group was kept as normal control. Treatment with 110 mg/ml/kg curcumin showed significant mean differences in the average white blood cell (WBC) count (p<0.05), cell infiltration, bone and cartilage erosion scores (p<0.05) compared to the olive oil treated group. Pannus formation scores showed that curcumin supplementation successfully suppressed the pannus formation process that occurred in the articular cartilage of the CIA joints. The mean difference for histological scores for the curcumin group was insignificant compared to the betamethasone treated group. It is concluded that supplementation of curcumin has protective effect on the histopathological and degenerative changes in the joints of CIA rats which was at par with betamethasone. PMID- 27366140 TI - Effect of methanolic extract of Piper sarmentosum leaves on neointimal foam cell infiltration in rabbits fed with high cholesterol diet. AB - Previous research has shown the beneficial effects of aqueous extract of Piper sarmentosum (P.s) on atherosclerosis. The first stage in atherosclerosis is the formation of foam cell. The aim of this study was to investigate the effect of the methanol extract of P.s on fatty streaks by calculating neointimal foam cell infiltration in rabbits fed with high cholesterol diet. Thirty six male New Zealand white rabbits were divided equally into six groups: (i) C: control group fed normal rabbit chow; (ii) CH: cholesterol diet (1 % cholesterol); (iii) PM1: 1 % cholesterol with methanol extract of P.s (62.5 mg/kg); (iv) PM2: 1 % cholesterol with methanol extract of P.s (125 mg/kg); (v) PM3: 1 % cholesterol with methanol extract of P.s (250 mg/kg); (vi) SMV group fed 1 % cholesterol supplemented with Simvistatin drug (1.2 mg/kg). All animals were treated for 10 weeks. At the end of the treatment, the rabbits were fasted and sacrificed and the aortic tissues were collected for histological studies to measure the area of the neointimal foam cell infiltration using software. The thickening of intima ratio of atherosclerosis and morphological changes by scanning electron microscope were measured. The results showed that the atherosclerotic group had significantly bigger area of fatty streak compared to the control group. The area of fatty streak in the abdominal aorta was significantly reduced in the treatment groups which were similar with the SMV group. Similarly, there was a reduction in the number of foam cell in the treatment groups compared to the atherosclerotic group as seen under scanning microscope. In conclusion, histological study demonstrated that the methanol extract of the P.s could reduce the neointimal foam cell infiltration in the lumen of the aorta and the atherosclerotic lesion. PMID- 27366141 TI - Chemical composition and anti-inflammatory effects of essential oil from Hallabong flower. AB - A number of essential oils derived from plants are claimed to have several medicinal functions, including anti-cancer and anti-inflammation effects. However, the chemical composition and biological activities of flower-derived components have not been sufficiently characterized. Therefore, we investigated the composition of essential oils from Hallabong flower [(Citrus unshiu Marcov * Citrus sinensis Osbeck) * Citrus reticulata Blanco] and their anti-inflammatory effects. Hydro-distilled essential oils (HEOs) were analyzed using gas chromatography-mass spectrometry (GC-MS). In total, 21 components were identified, representing more than 98 % of the oils, with sabinene (34.75 %), linalool (14.77 %), beta-ocimene (11.07 %), 4-terpineol (9.63 %), l-limonene (5.88 %), and gamma-terpinene (4.67 %) as the main components. In the present study, we also investigated the anti-inflammatory effects of HEOs on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. HEOs were found to inhibit nitric oxide (NO) and prostaglandin E2 (PGE2) production and to suppress the LPS-induced expression of cyclooxygenase-2 (COX-2) protein. In addition, HEOs downregulated the production of the inflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1beta (IC50 values are 0.05 %, 0.02 %, and 0.01 %, respectively). On the basis of these results, we suggest that HEOs can be considered potential anti-inflammatory candidates for therapeutic use in humans. PMID- 27366142 TI - Recent developments on potential new applications of emetine as anti-cancer agent. PMID- 27366143 TI - Separation of glycine-rich proteins from sea hare eggs and their anti-cancer activity against U937 leukemia cell line. AB - The present study was designed to investigate the anti-cancer effects of Sea hare eggs (SE) in U937 cells and its major active components. The aqueous extract of SE (ASE), which contained the highest protein content, dose-dependently inhibited the cancer cell's growth (IC50 value, 10.42 +/- 0.5 ug/mL). Additionally, ASE markedly caused DNA damage by inducing apoptotic body formation, DNA fragmentation, and accumulation of sub-G1 DNA contents. ASE induced apoptosis by activating caspase-3 and 9 and poly (ADP-ribose) polymerase (PARP) by regulating the expression of Bcl-2/Bax. Moreover, among its molecular weight fractions, the > 30 kDa fraction showed the highest cell-growth-inhibitory effects, which was inhibited by heat treatment. Furthermore, the > 30 kDa fraction had markedly higher glycine content than the ASE. The presence of two protein bands at around 16 and 32 kDa was identified. In addition, two fractions, F1 and F2, were obtained using anion-exchange chromatography, with the F1 having an improved cell growth-inhibitory effect than the > 30 kDa fraction. Taken together, these results suggest that the ASE contains glycine-rich proteins, including the active 16 and 32 kDa proteins, which account for its anti-cancer effects by inducing apoptosis via regulation of the mitochondrial pathway. PMID- 27366144 TI - The relationship between serology of hepatitis E virus with liver and kidney function in kidney transplant patients. AB - Although hepatitis E virus (HEV) is well known to cause acute hepatitis, there are reports showing that HEV may also be responsible for progression of acute to chronic hepatitis and liver cirrhosis in patients receiving organ transplantation. In this study, we aimed to evaluate the prevalence of HEV in patients with kidney transplantation. In this study, 110 patients with kidney transplantation were recruited, and anti-HEV IgG, creatinine, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and estimated glomerular filtration rate (eGFR) in the first, third and sixth months after renal transplantation were measured. The mean serum anti-HEV IgG titers in the study participants was 1.36 (range 0.23 to 6.3). Twenty-three patients were found to be seropositive for HEV Ab defined as anti-HEV IgG titer > 1.1. The difference in liver and renal function tests (creatinine, eGFR, AST, ALT and ALP) at different intervals was not significant between patients with HEV Ab titers higher and lower than 1.1 (p > 0.05). However, an inverse correlation was observed between HEV Ab and eGFR values in the first (p = 0.047, r = -0.21), third (p = 0.04, r = -0.20) and sixth (p = 0.04, r = -0.22) months after renal transplantation in patients with HEV Ab < 1.1 but not in the subgroup with HEV Ab > 1.1. Also, a significant correlation between age and HEV Ab levels was found in the entire study population (p = 0.001, r = 0.33). Our findings showed a high prevalence of seropositivity for anti-HEV IgG in patients receiving renal transplants. However, liver and renal functions were not found to be significantly different seropositive and seronegative patients by up to 6 months post-transplantation. PMID- 27366146 TI - Neural Net Gains Estimation Based on an Equivalent Model. AB - A model of an Equivalent Artificial Neural Net (EANN) describes the gains set, viewed as parameters in a layer, and this consideration is a reproducible process, applicable to a neuron in a neural net (NN). The EANN helps to estimate the NN gains or parameters, so we propose two methods to determine them. The first considers a fuzzy inference combined with the traditional Kalman filter, obtaining the equivalent model and estimating in a fuzzy sense the gains matrix A and the proper gain K into the traditional filter identification. The second develops a direct estimation in state space, describing an EANN using the expected value and the recursive description of the gains estimation. Finally, a comparison of both descriptions is performed; highlighting the analytical method describes the neural net coefficients in a direct form, whereas the other technique requires selecting into the Knowledge Base (KB) the factors based on the functional error and the reference signal built with the past information of the system. PMID- 27366145 TI - Daily Activity Abilities in MCI, Alzheimer's Disease, and Healthy Controls. AB - Mild cognitive impairment (MCI) is a risk state for dementia. The present study assessed daily functioning in MCI individuals (amnestic [aMCI] and nonamnestic [naMCI]) relative to those with Alzheimer's disease (AD) and healthy controls (NC). Twenty AD participants, 14 aMCI, 12 naMCI, and 30 healthy controls were administered the Direct Assessment of Functional Status (DAFS). The AD group performed poorer than all groups on all DAFS subscales. The aMCI group performed poorer than controls on the shopping subtests, while the naMCI group performed poorer than controls on only the free recall shopping. Finally, DAFS subscales discriminated the AD and aMCI groups well, but only recognition shopping discriminated between naMCI and aMCI individuals. These findings suggest that circumscribed ADL deficits distinguish subtypes of MCI and AD. PMID- 27366147 TI - An Analysis of the Effects of Smartphone Push Notifications on Task Performance with regard to Smartphone Overuse Using ERP. AB - Smartphones are used ubiquitously worldwide and are essential tools in modern society. However, smartphone overuse is an emerging social issue, and limited studies have objectively assessed this matter. The majority of previous studies have included surveys or behavioral observation studies. Since a previous study demonstrated an association between increased push notifications and smartphone overuse, we investigated the effects of push notifications on task performance. We detected changes in brainwaves generated by smartphone push notifications using the N200 and P300 components of event-related potential (ERP) to investigate both concentration and cognitive ability. ERP assessment indicated that, in both risk and nonrisk groups, the lowest N200 amplitude and the longest latency during task performance were found when push notifications were delivered. Compared to the nonrisk group, the risk group demonstrated lower P300 amplitudes and longer latencies. In addition, the risk group featured a higher rate of error in the Go-Nogo task, due to the negative influence of smartphone push notifications on performance in both risk and nonrisk groups. Furthermore, push notifications affected subsequent performance in the risk group. PMID- 27366148 TI - FullSSR: Microsatellite Finder and Primer Designer. AB - Microsatellites are genomic sequences comprised of tandem repeats of short nucleotide motifs widely used as molecular markers in population genetics. FullSSR is a new bioinformatic tool for microsatellite (SSR) loci detection and primer design using genomic data from NGS assay. The software was tested with 2000 sequences of Oryza sativa shotgun sequencing project from the National Center of Biotechnology Information Trace Archive and with partial genome sequencing with ROCHE 454(r) from Caiman latirostris, Salvator merianae, Aegla platensis, and Zilchiopsis collastinensis. FullSSR performance was compared against other similar SSR search programs. The results of the use of this kind of approach depend on the parameters set by the user. In addition, results can be affected by the analyzed sequences because of differences among the genomes. FullSSR simplifies the detection of SSRs and primer design on a big data set. The command line interface of FullSSR was intended to be used as part of genomic analysis tools pipeline; however, it can be used as a stand-alone program because the results are easily interpreted for a nonexpert user. PMID- 27366150 TI - The Reinforcement Effect of Nano-Zirconia on the Transverse Strength of Repaired Acrylic Denture Base. AB - Objective. The aim of this study was to evaluate the effect of incorporation of glass fiber, zirconia, and nano-zirconia on the transverse strength of repaired denture base. Materials and Methods. Eighty specimens of heat polymerized acrylic resin were prepared and randomly divided into eight groups (n = 10): one intact group (control) and seven repaired groups. One group was repaired with autopolymerized resin while the other six groups were repaired using autopolymerized resin reinforced with 2 wt% or 5 wt% glass fiber, zirconia, or nano-zirconia particles. A three-point bending test was used to measure the transverse strength. The results were analyzed using SPSS and repeated measure ANOVA and post hoc least significance (LSD) test (P <= 0.05). Results. Among repaired groups it was found that autopolymerized resin reinforced with 2 or 5 wt% nano-zirconia showed the highest transverse strength (P <= 0.05). Repairs with autopolymerized acrylic resin reinforced with 5 wt% zirconia showed the lowest transverse strength value. There was no significant difference between the groups repaired with repair resin without reinforcement, 2 wt% zirconia, and glass fiber reinforced resin. Conclusion. Reinforcing of repair material with nano-zirconia may significantly improve the transverse strength of some fractured denture base polymers. PMID- 27366151 TI - Intracavitary Irradiation as a Safe Alternative for Cystic Craniopharyngiomas: Case Report and Review of the Literature. AB - Craniopharyngioma treatment remains a challenge for clinicians and patients. There are many treatment alternatives; however one of them (intracavitary irradiation) seeks to control this type of benign brain tumor using minimally invasive techniques, with the specific aim of avoiding causing significant damage to important structures surrounding the sellar/suprasellar region. We present the case of a 3-year-old patient with a predominantly cystic craniopharyngioma who underwent intracavitary irradiation by stereotactic placement. Using this approach, the patient showed a successful response with remission of headaches and hydrocephalus. A reduction in the size of the cyst was achieved, without deterioration of visual fields, with no hormonal supplementation being needed, and with no evidence of focal neurological signs. PMID- 27366149 TI - 3D-Printed Scaffolds and Biomaterials: Review of Alveolar Bone Augmentation and Periodontal Regeneration Applications. AB - To ensure a successful dental implant therapy, the presence of adequate vertical and horizontal alveolar bone is fundamental. However, an insufficient amount of alveolar ridge in both dimensions is often encountered in dental practice due to the consequences of oral diseases and tooth loss. Although postextraction socket preservation has been adopted to lessen the need for such invasive approaches, it utilizes bone grafting materials, which have limitations that could negatively affect the quality of bone formation. To overcome the drawbacks of routinely employed grafting materials, bone graft substitutes such as 3D scaffolds have been recently investigated in the dental field. In this review, we highlight different biomaterials suitable for 3D scaffold fabrication, with a focus on "3D printed" ones as bone graft substitutes that might be convenient for various applications related to implant therapy. We also briefly discuss their possible adoption for periodontal regeneration. PMID- 27366152 TI - Cardiac Arrest and Gastrointestinal Bleeding: A Case of Medical Heuristics. AB - Insufficient clinical data from patients is a major cause of errors in medical diagnostics. In an attempt to make a diagnosis, initial clinical information provided to the physician may be overly relied on as the only information required in making diagnosis leading to anchoring. Failure to rely on differential diagnoses in spite of new signs and symptoms or rethinking of initial hypothesis may lead to fixation on a certain diagnosis, which may lead to significant morbidity and mortality. In the event that there is an anchoring heuristic, like in our patient, it is important to consider differential diagnoses; however, it is not wrong to rely on some form of anchor. We report a case of a 62-year-old male with a history of multiple medical conditions and a history of acetaminophen overdose who presented to the hospital with large amounts of coffee ground emesis. He was subsequently transferred to the liver transplant center on discovery that he was in fulminant hepatic failure and died two days later in spite of aggressive medical treatment. PMID- 27366154 TI - Aryl Hydrocarbon Receptor Deficiency in an Exon 3 Deletion Mouse Model Promotes Hematopoietic Stem Cell Proliferation and Impacts Endosteal Niche Cells. AB - The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor belonging to the Per-Arnt-Sim (PAS) family of proteins. The AHR is involved in hematopoietic stem cell (HSC) functions including self-renewal, proliferation, quiescence, and differentiation. We hypothesize that AHR impacts HSC functions by influencing genes that have roles in HSC maintenance and function and that this may occur through regulation of bone marrow (BM) niche cells. We examined BM and niche cells harvested from 8-week-old AHR null-allele (KO) mice in which exon 3 was deleted in the Ahr gene and compared these data to cells from B6 control mice; young and old (10 months) animals were also compared. We report changes in HSCs and peripheral blood cells in mice lacking AHR. Serial transplantation assays revealed a significant increase in long term HSCs. There was a significant increase in mesenchymal stem cells constituting the endosteal BM niche. Gene expression analyses of HSCs revealed an increase in expression of genes involved in proliferation and maintenance of quiescence. Our studies infer that loss of AHR results in increased proliferation and self-renewal of long term HSCs, in part, by influencing the microenvironment in the niche regulating the balance between quiescence and proliferation in HSCs. PMID- 27366153 TI - Osteosarcoma: Cells-of-Origin, Cancer Stem Cells, and Targeted Therapies. AB - Osteosarcoma (OS) is the most common type of primary solid tumor that develops in bone. Although standard chemotherapy has significantly improved long-term survival over the past few decades, the outcome for those patients with metastatic or recurrent OS remains dismally poor and, therefore, novel agents and treatment regimens are urgently required. A hypothesis to explain the resistance of OS to chemotherapy is the existence of drug resistant CSCs with progenitor properties that are responsible of tumor relapses and metastasis. These subpopulations of CSCs commonly emerge during tumor evolution from the cell-of origin, which are the normal cells that acquire the first cancer-promoting mutations to initiate tumor formation. In OS, several cell types along the osteogenic lineage have been proposed as cell-of-origin. Both the cell-of-origin and their derived CSC subpopulations are highly influenced by environmental and epigenetic factors and, therefore, targeting the OS-CSC environment and niche is the rationale for many recently postulated therapies. Likewise, some strategies for targeting CSC-associated signaling pathways have already been tested in both preclinical and clinical settings. This review recapitulates current OS cell-of origin models, the properties of the OS-CSC and its niche, and potential new therapies able to target OS-CSCs. PMID- 27366155 TI - Outbreak of Norovirus GII.P17-GII.17 in the Canadian Province of Nova Scotia. AB - Background. Norovirus is the leading cause of viral gastroenteritis, with GII.4 being the most common circulating genotype. Recently, outbreaks in China revealed that norovirus GII.17 GII.P17 had become predominant. Objective. This study aimed to characterize the distribution of norovirus genotypes circulating in Nova Scotia. Methods. Stool specimens were collected from gastrointestinal outbreaks in Nova Scotia between Jan 2014 and June 2015 and subjected to real-time RT-PCR. Norovirus-positive specimens were referred to the National Microbiology Laboratory for sequence-based genotyping. Results. The first norovirus GII.P17 GII.17 outbreak in Canada was identified, but no widespread activity was observed in Nova Scotia. Discussion. It is unknown whether GII.P17-GII.17 is more widespread in Canada since contributions to Canadian surveillance are too sparse to effectively monitor the epidemiology of emerging norovirus genotypes. Conclusions. Presence of norovirus GII.17:P17 in Canada highlights the need for more systematic surveillance to ensure that molecular targets used for laboratory detection are effective and help understand norovirus evolution, epidemiology, and pathogenesis. PMID- 27366156 TI - Helminthic Infection and Nutritional Studies among Orang Asli Children in Sekolah Kebangsaan Pos Legap, Perak. AB - Background. Orang Asli (aborigine) children are susceptible to soil-transmitted helminth (STH) infections due to their lifestyle and substandard sanitation system. Objectives. This study aimed to examine the helminthic and nutritional status of Orang Asli school children in Sekolah Kebangsaan Pos Legap, a remote primary school at Kuala Kangsar District in the state of Perak, Malaysia. In addition, the sensitivities of four STH stool examination techniques were also compared. Methods. Demography and anthropometry data were collected by one-to-one interview session. Collected stools were examined with four microscopy techniques, namely, direct wet mount, formalin ether concentration (FEC), Kato Katz (KK), and ParasepTM. Results. Anthropometry analysis showed that 78% (26/33) of children in SK Pos Legap were malnourished and 33% (11/33) of them were stunted. Stool examinations revealed almost all children (97%) were infected by either one of the three commonest STHs. FEC was the most sensitive method in detection of the three helminth species. Conclusion. This study revealed that STH infections and nutritional status still remain a health concern among the Orang Asli children. These communal problems could be effectively controlled by regular monitoring of STH infection loads, administration of effective antihelminthic drug regimen, and also implementation of effective school nutritional programs. PMID- 27366157 TI - Measles Outbreak among Previously Immunized Adult Healthcare Workers, China, 2015. AB - Measles is caused by measles virus belonging to genus Morbillivirus of the family Paramyxoviridae. Vaccination has played a critical role in controlling measles infection worldwide. However, in the recent years, outbreaks of measles infection still occur in many developing countries. Here, we report an outbreak of measles among healthcare workers and among the 60 measles infected patients 50 were healthcare workers including doctors, nurses, staff, and medics. Fifty-one patients (85%) tested positive for IgM antibodies against the measles virus and 50 patients (83.3%) tested positive for measles virus RNA. Surprisingly, 73.3% of the infected individuals had been previously immunized against measles. Since there is no infection division in our hospital, the fever clinics are located in the Emergency Division. In addition, the fever and rash were not recognized as measles symptoms at the beginning of the outbreak. These factors result in delay in isolation and early confirmation of the suspected patients and eventually a measles outbreak in the hospital. Our report highlights the importance of following a two-dose measles vaccine program in people including the healthcare workers. In addition, vigilant attention should be paid to medical staff with clinical fever and rash symptoms to avoid a possible nosocomial transmission of measles infection. PMID- 27366158 TI - Fosfomycin: A First-Line Oral Therapy for Acute Uncomplicated Cystitis. AB - Fosfomycin is a new agent to Canada approved for the treatment of acute uncomplicated cystitis (AUC) in adult women infected with susceptible isolates of E. coli and Enterococcus faecalis. We reviewed the literature regarding the use of oral fosfomycin for the treatment of AUC. All English-language references from 1975 to October 2015 were reviewed. In Canada, fosfomycin tromethamine is manufactured as Monurol(r) and is available as a 3-gram single dose sachet. Fosfomycin has a unique chemical structure, inhibiting peptidoglycan synthesis at an earlier site compared to beta-lactams with no cross-resistance with other agents. Fosfomycin displays broad-spectrum activity against ESBL-producing, AmpC producing, carbapenem-non-susceptible, and multidrug-resistant (MDR) E. coli. Resistance to fosfomycin in E. coli is rare (<1%). Fosfomycin is excreted unchanged in the urine by glomerular filtration with peak urinary concentration ~4000 ug/mL and remains at concentrations >100 ug/mL for 48 hours after a single 3-gram oral dose. No dosage adjustments are required in elderly patients, in pregnant patients, or in either renal or hepatic impairment. Fosfomycin demonstrates a favorable safety profile, and clinical trials have demonstrated efficacy in AUC that is comparable to ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole. Fosfomycin's in vitro activity against common uropathogens, including MDR isolates, its favorable safety profile including pregnancy patients, drug interactions, and clinical trials data demonstrating efficacy in AUC, has resulted in Canadian, US, and European guidelines/authorities recommending fosfomycin as a first line agent for the treatment of AUC. PMID- 27366159 TI - Death of a 29-Year-Old Male from Undifferentiated Sepsis. AB - Tumour necrosis factor alpha inhibitors, such as infliximab, and other biologic agents are associated with increased risk of opportunistic infection, including tuberculosis. Tuberculosis infections associated with infliximab tend to present atypically and can be difficult to diagnose, as they are more likely to manifest as extrapulmonary or disseminated disease. The authors report a case involving a 29-year-old male patient who died following 16 days of treatment for undifferentiated sepsis and who was found on autopsy to have widespread disseminated tuberculosis. Prior to the onset of illness, the patient had received infliximab for the treatment of Crohn's disease. Following discussion of the case, the authors review the definition of adverse events, provide a root cause analysis of the cognitive errors and breakdowns in the health care system that contributed to the reported outcome, and identify opportunities to address these breakdowns and improve patient safety measures for future cases. PMID- 27366160 TI - A Cluster of Three Cases of Hantavirus Pulmonary Syndrome among Canadian Military Personnel. AB - Hantavirus pulmonary syndrome (HPS) is a rare illness in eastern Canada. We present three cases of HPS among military personnel in Quebec. The three cases shared a common exposure to mouse excreta while engaged in military training in Alberta, a western province of Canada. PMID- 27366161 TI - HIV Prophylaxis in High Risk Newborns: An Examination of Sociodemographic Factors in an Inner City Context. AB - Background. Perinatal HIV transmission is less than 1% with antiretroviral (ARV) prophylaxis. Transmission risk appears higher in "high risk" dyads, yet this is not well defined, possibly exposing more infants to combination ARV compared with standard care. Objective. To describe characteristics of mother-infant dyads where infants received ARVs and how these characteristics relate to specific ARV regimens. Methods. Retrospective chart review of ARV-receiving newborns at St. Michael's Hospital from 2007 to 2012 (and their mothers). Numerical and categorical variables were analyzed using t-tests/ANOVA F-tests and Fisher's exact tests, respectively. Results. Maternal HIV status at delivery was as follows: 69% positive and 24% unknown. Maternal factors significantly associated with newborn-triple therapy are Canadian origin, substance abuse, unstable housing, lost custody of previous children, and sex work. Neonatal factors are child protective services involvement, NICU, and lengthier admission. Maternal factors associated with monotherapy are African origin, HIV-positive, employment, and education. Further analysis based on maternal presentation at delivery demonstrated unequal distribution of many aforementioned factors. Discussion. This cohort revealed associations between particular factors and newborn monotherapy or triple therapy that exist, suggesting that sociodemographic factors may influence the choice of ARV regimen. Canadian perinatal HIV transmission guidelines should qualify how to risk stratify newborns and consider use of rapid HIV antibody testing. PMID- 27366162 TI - A Fatal Case of Necrotizing Fasciitis Caused by a Highly Virulent Escherichia coli Strain. AB - Necrotizing fasciitis is a serious disease characterized by the necrosis of the subcutaneous tissues and fascia. E. coli as the etiologic agent of necrotizing fasciitis is a rare occurrence. A 66-year-old woman underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. She rapidly developed necrotizing fasciitis which led to her death 68 hours following surgery. An E. coli strain was isolated from blood and fascia cultures. DNA microarray revealed the presence of 20 virulence genes. PMID- 27366163 TI - First Imported Case of Chikungunya Virus Infection in a Travelling Canadian Returning from the Caribbean. AB - This is the first Canadian case of Chikungunya virus (CHIKV) infection reported in a traveller returning from the Caribbean. Following multiple mosquito bites in Martinique Island in January 2014, the patient presented with high fever, headaches, arthralgia on both hands and feet, and a rash on the trunk upon his return to Canada. Initial serological testing for dengue virus infection was negative. Support therapy with nonsteroidal anti-inflammatory drugs was administered. The symptoms gradually improved 4 weeks after onset with residual arthralgia and morning joint stiffness. This clinical feature prompted the clinician to request CHIKV virus serology which was found to be positive for the presence of IgM and neutralizing antibodies. In 2014, over four hundred confirmed CHIKV infection cases were diagnosed in Canadian travellers returning from the Caribbean and Central America. Clinical suspicion of CHIKV or dengue virus infections should be considered in febrile patients with arthralgia returning from the recently CHIKV endemic countries of the Americas. PMID- 27366164 TI - Human Papilloma Virus Persistence after Cone Excision in Women with Cervical High Grade Squamous Intraepithelial Lesion: A Prospective Study. AB - Background. Persistent human papillomavirus (HPV) infection is a necessary event in cervical cancer tumorigenesis. Our objectives were to estimate the rate of HPV infection persistence after large loop excision of the transformation zone (LEEP) in patients with high grade squamous intraepithelial lesions (HSIL) and to investigate if HPV persistence is type related. Methods. We conducted a prospective study on 89 patients with HSIL treated with LEEP. DNA HPV was performed before surgery and at 6, 12, and 18 months after LEEP. Results. Four patients were excluded from the study. The HPV persistence in the remaining 85 patients was 32.95% (6 months), 14.12% (12 months), and 10.59% (18 months). Type 16 had the highest persistence rate, 23.5% (6 months), 11.8% (12 months), and 8.2% (18 months). Coinfection was found to be 54.12% before LEEP and 18.8% (6 months), 4.7% (12 months), and 3.5% (18 months) after LEEP. The rate of coinfections including type 16 was 46.83% of all coinfections. Coinfection including type 16 was not correlated with higher persistence rate compared to infection with type 16 only. Conclusions. HPV infection is not completely eradicated by LEEP in patients with HSIL lesion on PAP smear. HPV persistence after LEEP is influenced by HPV type. HPV type 16 has the highest persistence rate. PMID- 27366165 TI - Bacillus pumilus Septic Arthritis in a Healthy Child. AB - We report a case of septic arthritis caused by a Bacillus species, B. pumilus, occurring in a healthy child. This organism rarely causes serious infections and has only been described in newborns and immunocompromised individuals or as a skin infection. This child developed an indolent joint swelling after a minor skin injury, and symptoms were initially thought most consistent with chronic arthritis. The case demonstrates that clinicians should consider joint infection in children presenting with acute monoarticular swelling, even without prominent systemic features. PMID- 27366166 TI - Antineutrophil Cytoplasmic Antibody Induction due to Infection: A Patient with Infective Endocarditis and Chronic Hepatitis C. AB - While antineutrophil cytoplasmic antibody (ANCA) is often used as a diagnostic marker for certain vasculitides, ANCA induction in the setting of infection is much less common. In the case of infective endocarditis, patients may present with multisystem disturbances resembling an autoimmune process, cases that may be rendered even trickier to diagnose in the face of a positive ANCA. Though not always straightforward, distinguishing an infective from an inflammatory process is pivotal in order to guide appropriate therapy. We describe an encounter with a 43-year-old male with chronically untreated hepatitis C virus infection who featured ANCA positivity while hospitalized with acute bacterial endocarditis. His case serves as a reminder of two of the few infections known to uncommonly generate ANCA positivity. We also summarize previously reported cases of ANCA positivity in the context of endocarditis and hepatitis C infections. PMID- 27366167 TI - Comparative Evaluation of the BD Phoenix Yeast ID Panel and Remel RapID Yeast Plus System for Yeast Identification. AB - Becton Dickinson Phoenix Yeast ID Panel was compared to the Remel RapID Yeast Plus System using 150 recent clinical yeast isolates and the API 20C AUX system to resolve discrepant results. The concordance rate between the Yeast ID Panel and the RapID Yeast Plus System (without arbitration) was 93.3% with 97.3% (146/150) and 95.3% (143/150) of the isolates correctly identified by the Becton Dickinson Phoenix and the Remel RapID, respectively, with arbitration. PMID- 27366168 TI - Review of 16S and ITS Direct Sequencing Results for Clinical Specimens Submitted to a Reference Laboratory. AB - We evaluated the performance of 16S and internal transcribed spacer (ITS) region amplification and sequencing of rDNA from clinical specimens, for the respective detection and identification of bacterial and fungal pathogens. Direct rDNA amplification of 16S and ITS targets from clinical samples was performed over a 4 year period and reviewed. All specimens were from sterile sites and submitted to a reference laboratory for evaluation. Results of 16S and ITS were compared to histopathology, Gram and/or calcofluor stain microscopy results. A total of 277 16S tests were performed, with 64 (23%) positive for the presence of bacterial DNA. Identification of an organism was more likely in microscopy positive 16S samples 14/21 (67%), compared to 35/175 (20%) of microscopy negative samples. A total of 110 ITS tests were performed, with 14 (13%) positive. The yield of microscopy positive ITS samples, 9/44 (21%), was higher than microscopy negative samples 3/50 (6%). Given these findings, 16S and ITS are valuable options for culture negative specimens from sterile sites, particularly in the setting of positive microscopy findings. Where microscopy results are negative, the limited sensitivity of 16S and ITS in detecting and identifying an infectious agent needs to be considered. PMID- 27366169 TI - A Case of Polyarticular Pasteurella multocida Septic Arthritis. AB - A 76-year-old man with a history of osteoarthritis presents with right leg erythema and inability to weight-bear and pain in his right shoulder. Synovial fluid cell count of the knee and shoulder showed abundant neutrophils, and cultures of the knee showed growth of Pasteurella multocida. The patient owned four cats with which he had frequent contact, but history and physical examination elicited no evidence of scratches or bites. This case highlights the invasive potential of Pasteurella multocida in an immunocompetent individual and its capacity to cause septic arthritis in the setting of frequent animal contact. PMID- 27366170 TI - Genomic Analysis of a Serotype 5 Streptococcus pneumoniae Outbreak in British Columbia, Canada, 2005-2009. AB - Background. Streptococcus pneumoniae can cause a wide spectrum of disease, including invasive pneumococcal disease (IPD). From 2005 to 2009 an outbreak of IPD occurred in Western Canada, caused by a S. pneumoniae strain with multilocus sequence type (MLST) 289 and serotype 5. We sought to investigate the incidence of IPD due to this S. pneumoniae strain and to characterize the outbreak in British Columbia using whole-genome sequencing. Methods. IPD was defined according to Public Health Agency of Canada guidelines. Two isolates representing the beginning and end of the outbreak were whole-genome sequenced. The sequences were analyzed for single nucleotide variants (SNVs) and putative genomic islands. Results. The peak of the outbreak in British Columbia was in 2006, when 57% of invasive S. pneumoniae isolates were serotype 5. Comparison of two whole-genome sequenced strains showed only 10 SNVs between them. A 15.5 kb genomic island was identified in outbreak strains, allowing the design of a PCR assay to track the spread of the outbreak strain. Discussion. We show that the serotype 5 MLST 289 strain contains a distinguishing genomic island, which remained genetically consistent over time. Whole-genome sequencing holds great promise for real-time characterization of outbreaks in the future and may allow responses tailored to characteristics identified in the genome. PMID- 27366171 TI - Simulating Immune Interference on the Effect of a Bivalent Glycoconjugate Vaccine against Haemophilus influenzae Serotypes "a" and "b". AB - Objective. We sought to evaluate the immune responses to a bivalent Haemophilus influenzae glycoconjugate vaccine against serotypes "a" (Hia) and "b" (Hib) in the presence of the preexisting immunity to Hib. Methods. We developed a stochastic simulation model of humoral immune response to investigate the antigenic challenge of a bivalent combined glycoconjugate vaccine and a bivalent unimolecular glycoconjugate vaccine. We compared simulation outcomes in the absence of any preexisting immunity with an already primed immune response having specific memory B cells and/or anti-Hib antibodies. Results. The simulation results show that the preexisting immune responses to Hib or carrier protein (CP) may significantly impede the production of anti-Hia antibodies by a unimolecular vaccine. In contrast, the production of anti-Hia antibodies using a combined vaccine is inhibited only in the presence of CP immune responses. Conclusions. Preexisting immunity to Hib and CP may play a critical role in the development of immune responses against Hia or Hib using bivalent combined and unimolecular vaccine formulations. Our results suggest that a bivalent combined glycoconjugate vaccine with a carrier protein not previously used in Hib conjugate vaccines may be an effective formulation for generating immune responses to protect against both Hib and Hia infections. PMID- 27366172 TI - The Performance of Direct Disk Diffusion for Community Acquired Bacteremia due to Gram-Negative Bacilli and Its Impact on Physician Treatment Decisions. AB - Background. Direct disk diffusion susceptibility testing provides faster results than standard microtitre susceptibility. The direct result may impact patient outcome in sepsis if it is accurate and if physicians use the information to promptly and appropriately change antibiotic treatment. Objective. To compare the performance of direct disk diffusion with standard susceptibility and to consider physician decisions in response to these early results, for community acquired bacteremia with Gram-negative Bacilli. Methods. Retrospective observational study of all positive blood cultures with Gram-negative Bacilli, collected over one year. Physician antibiotic treatment decisions were assessed by an infectious diseases physician based on information available to the physician at the time of the decision. Results. 89 bottles growing Gram-negative Bacilli were included in the analysis. Direct disk diffusion agreement with standard susceptibility varied widely. In 47 cases (52.8%), the physician should have changed to a narrower spectrum but did not, in 18 cases (20.2%), the physician correctly narrowed from appropriate broad coverage, and in 8 cases (9.0%), the empiric therapy was correct. Discussion. Because inoculum is not standardized, direct susceptibility results do not agree with standard susceptibility results for all drugs. Physicians do not act on direct susceptibility results. Conclusion. Direct susceptibility should be discontinued in clinical microbiology laboratories. PMID- 27366173 TI - Ertapenem Articulating Spacer for the Treatment of Polymicrobial Total Knee Arthroplasty Infection. AB - Introduction. Periprosthetic joint infections (PJIs) are the primary cause of early failure of the total knee arthroplasty (TKA). Polymicrobial TKA infections are often associated with a higher risk of treatment failure. The aim of the study was to assess the efficacy of ertapenem loaded spacers in the treatment of polymicrobial PJI. Methods. There were 18 patients enrolled; nine patients with polymicrobial PJI treated with ertapenem loaded articulating spacers were compared to the group of 9 patients treated with vancomycin or ceftazidime loaded spacers. Results. Successful reimplantation with revision implants was possible in 66.67%. Ertapenem spacers were used in 6 cases in primary two-stage procedure and in 3 cases in secondary spacer exchange. Successful infection eradication was achieved in all cases; final reimplantation with revision knee arthroplasty implants was possible in 6 cases. Conclusion. Ertapenem can be successfully used as antimicrobial addition to the cement spacers in two-stage revision treatment of polymicrobial PJIs. However, this type of spacer may also be useful in the treatment of infections caused by monomicrobial extended spectrum beta-lactamases producing gram-negative bacilli. Further clinical studies are required to evaluate the efficacy and safety of ertapenem spacers in the treatment of polymicrobial and monomicrobial PJIs. PMID- 27366174 TI - Schistosomiasis Presenting as a Case of Acute Appendicitis with Chronic Mesenteric Thrombosis. AB - The manifestations of schistosomiasis typically result from the host inflammatory response to parasitic eggs that are deposited in the mucosa of either the gastrointestinal tract or bladder. We present here a case of a 50-year-old gentleman with a rare gastrointestinal presentation of both schistosomal appendicitis and mesenteric thrombosis. PMID- 27366175 TI - Infections Caused by Actinomyces neuii: A Case Series and Review of an Unusual Bacterium. AB - Background. Actinomyces neuii is a Gram-positive bacillus rarely implicated in human infections. However, its occurrence is being increasingly recognized with the use of improved identification systems. Objective. To analyse A. neuii infections in Alberta, Canada, and review the literature regarding this unusual pathogen. Methods. Cases of A. neuii were identified in 2013-2014 in Alberta. Samples were cultured aerobically and anaerobically. A predominant catalase positive Gram-positive coryneform bacillus with no branching was isolated in each case. Testing was initially done with API-CORYNE(r) (bioMerieux) and isolates were sent to the Provincial Laboratory for Public Health for further testing. Isolates' identities were confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry microbial identification system (MALDI-TOF MS MIS; bioMerieux) and/or DNA sequencing. Results. Six cases of A. neuii infection were identified. All patients had soft tissue infections; typically, incision and drainage were done followed by a course of antibiotics. Agents used included cephalexin, ertapenem, ciprofloxacin, and clindamycin. All had favourable outcomes. Conclusions. While A. neuii is infrequently recognized, it can cause a diverse array of infections. Increased use of MALDI-TOF MS MIS is leading to increased detection; thus, understanding the pathogenicity of this bacterium and its typical susceptibility profile will aid clinical decision making. PMID- 27366176 TI - Case Report of Necrotizing Fasciitis Associated with Streptococcus pneumoniae. AB - Necrotizing fasciitis, caused by Streptococcus pneumoniae, is an extremely rare and life-threatening bacterial soft tissue infection. We report a case of early necrotizing fasciitis associated with Streptococcus pneumoniae infection in a 26 year-old man who was immunocompromised with mixed connective tissue disease. The patient presented with acute, painful, erythematous, and edematous skin lesions of his right lower back, which rapidly progressed to the right knee. The patient underwent surgical exploration, and a diagnosis of necrotizing fasciitis was confirmed by pathological evidence of necrosis of the fascia and neutrophil infiltration in tissue biopsies. Cultures of fascial tissue biopsies and blood samples were positive for Streptococcus pneumoniae. To our knowledge, this is the first report of necrotizing fasciitis resulting from Streptococcus pneumoniae diagnosed at early phase; the patient recovered well without surgical debridement. PMID- 27366177 TI - Rat Bite Fever Resembling Rheumatoid Arthritis. AB - Rat bite fever is rare in Western countries. It can be very difficult to diagnose as blood cultures are typically negative and a history of rodent exposure is often missed. Unless a high index of suspicion is maintained, the associated polyarthritis can be mistaken for rheumatoid arthritis. We report a case of culture-positive rat bite fever in a 46-year-old female presenting with fever and polyarthritis. The clinical presentation mimicked rheumatoid arthritis. Infection was complicated by discitis, a rare manifestation. We discuss the diagnosis and management of this rare zoonotic infection. We also review nine reported cases of rat bite fever, all of which had an initial presumptive diagnosis of a rheumatological disorder. Rat bite fever is a potentially curable infection but can have a lethal course if left untreated. PMID- 27366178 TI - Chronic Q Fever in Alberta: A Case of Coxiella burnetii Mycotic Aneurysm and Concomitant Vertebral Osteomyelitis. AB - Chronic Q fever is a potentially life-threatening infection from the intracellular, Gram-negative Coxiella burnetii. It presents most commonly as endocarditis or vascular infection in people with underlying cardiac or vascular disease. We discuss a case of a 67-year-old male with Coxiella burnetii vascular infection of a perirenal abdominal aortic graft. The patient had a history of an abdominal aortic aneurysm (AAA) repair 5 years earlier. He presented with a 12 * 6 * 8 cm perirenal pseudoaneurysm and concomitant L1, L2, and L3 vertebral body discitis. He underwent an open repair which revealed a grossly infected graft perioperatively. Q fever serology revealed phase I serological IgG titer of 1 : 2048 and phase II 1 : 1024 consistent with chronic Q fever. Polymerase chain reaction (PCR) on infected vascular tissue was positive for C. burnetii. The patient was started on doxycycline and hydroxychloroquine with good clinical response and decreasing serological titers. Recognizing chronic Q fever is a difficult task as symptoms are nonspecific, exposure risk is difficult to ascertain, and diagnosis is hidden from conventional microbiological investigations. Its recognition, however, is critical as C. burnetii is inherently resistant to standard empiric therapies used in cardiovascular infections. PMID- 27366179 TI - Fidaxomicin versus Vancomycin in the Treatment of Clostridium difficile Infection: Canadian Outcomes. AB - Background. This analysis examined the efficacy of fidaxomicin versus vancomycin in 406 Canadian patients with Clostridium difficile infection (CDI), based on data from 2 randomized, clinical trials. Methods. Patients received fidaxomicin or vancomycin 1. Patients were assessed for clinical response recurrence of infection and sustained clinical response for 28 days after treatment completion. Patients at increased risk of recurrence were subjected to subgroup analyses. Results. Clinical response rates for fidaxomicin (90.0%) were noninferior to those with vancomycin (92.2%; 95% confidence interval for difference: -7.7, 3.5). However, fidaxomicin-treated patients had lower recurrence (14.4% versus 28.0%, p = 0.001) and higher sustained clinical response (77.1% versus 66.3%, p = 0.016). Compared with vancomycin, fidaxomicin was associated with lower recurrence rates in all subgroups, reaching statistical significance in patients with age >= 65 years (16.0% versus 30.9%, p = 0.026), concomitant antibiotic use (16.2% versus 38.7%, p = 0.036), and non-BI strains (11.8% versus 28.3%, p = 0.004). Higher sustained clinical response rates were observed for fidaxomicin compared with vancomycin in all subgroups; this was statistically significant in the non-BI subgroup (82.8% versus 69.1%, p = 0.021). Conclusions. In Canadian patients, fidaxomicin was superior to vancomycin in sustaining clinical response and reducing CDI recurrence. PMID- 27366180 TI - Association between Accessory Gene Regulator Polymorphism and Mortality among Critically Ill Patients Receiving Vancomycin for Nosocomial MRSA Bacteremia: A Cohort Study. AB - Background. Polymorphism of the accessory gene regulator group II (agr) in methicillin-resistant Staphylococcus aureus (MRSA) is predictive of vancomycin failure therapy. Nevertheless, the impact of group II agr expression on mortality of patients with severe MRSA infections is not well established. Objective. The goal of our study was to evaluate the association between agr polymorphism and all-cause in-hospital mortality among critically ill patients receiving vancomycin for nosocomial MRSA bacteremia. Methods. All patients with documented bacteremia by MRSA requiring treatment in the ICU between May 2009 and November 2011 were included in the study. Cox proportional hazards regression was performed to evaluate whether agr polymorphism was associated with all-cause in hospital mortality. Covariates included age, APACHE II score, initial C-reactive protein plasma levels, initial serum creatinine levels, vancomycin minimum inhibitory concentration, vancomycin serum levels, and time to effective antibiotic administration. Results. The prevalence of group I and group II agr expression was 52.4% and 47.6%, respectively. Bacteremia by MRSA group III or group IV agr was not documented in our patients. The mean APACHE II of the study population was 24.3 (standard deviation 8.5). The overall cohort mortality was 66.6% (14 patients). After multivariate analysis, initial plasma C-reactive protein levels (P = 0.01), initial serum creatinine levels (P = 0.008), and expression of group II agr (P = 0.006) were positively associated with all-cause in-hospital mortality. Patients with bacteremia by MRSA with group II agr expression had their risk of death increased by 12.6 times when compared with those with bacteremia by MRSA with group I agr expression. Conclusion. Group II agr polymorphism is associated with an increase in mortality in critically ill patients with bacteremia by MRSA treated with vancomycin. PMID- 27366182 TI - Successful Treatment of Hepatitis C with Simeprevir, Sofosbuvir, and Ribavirin in an HIV Coinfected Liver Transplant Patient with Advanced Chronic Kidney Disease. AB - Although major advances have occurred in treating patients with hepatitis C virus (HCV) with the development of new direct-acting antivirals (DAAs), treatment of liver transplant recipients with HCV, human immunodeficiency virus (HIV) coinfection, and renal disease is challenging due to the lack of efficacy and safety data in this population. We report a case of successful HCV therapy in a postliver transplant HIV coinfected patient, with stage 4 chronic kidney disease, using an all-oral regimen of simeprevir, sofosbuvir, and ribavirin. The 51-year old male achieved SVR24, and no specific HIV-related or transplant-related adverse events were documented during the treatment period. The new DAAs show promise for HIV coinfected patients and those with severe to end-stage renal disease (ESRD); however, robust clinical trials or large cohort studies will need to be conducted to confirm the efficacy and safety of these newer agents in this setting. PMID- 27366181 TI - Characterization of Clostridium difficile Strains in British Columbia, Canada: A Shift from NAP1 Majority (2008) to Novel Strain Types (2013) in One Region. AB - Background. Clostridium difficile is a major cause of gastrointestinal illness. Epidemic NAP1 strains contain toxins A and B, a deletion in repressor tcdC, and a binary toxin. Objectives. To determine the molecular epidemiology of C. difficile in British Columbia and compare between two time points in one region. Methods. C. difficile isolates from hospital and community laboratories (2008) and one Island Health hospital laboratory (2013) were characterized by pulsed-field gel electrophoresis, PCR-ribotyping, toxin possession, tcdC genotype, and antimicrobial susceptibility. Results. In 2008, 42.7% of isolates had NAP1 designation. Hospital-collected isolates were associated with older patients and more NAP1 types. Unlike other isolates, most NAP1 isolates possessed binary toxin and a 19 bp loss in tcdC. All isolates were susceptible to metronidazole and vancomycin. A 2013 follow-up revealed a 28.9% decrease in NAP1 isolates and 20.0% increase in isolates without NAP designation in one region. Then, community associated cases were seen in younger patients, while NAP types were evenly distributed. Isolates without NAP designation did not cluster with a PFGE pattern or ribotype. Conclusions. Evaluation of C. difficile infections within British Columbia revealed demographic associations, epidemiological shifts, and characteristics of strain types. Continuous surveillance of C. difficile will enable detection of emerging strains. PMID- 27366183 TI - Patient Characteristics and Outcomes of Outpatient Parenteral Antimicrobial Therapy: A Retrospective Study. AB - Outpatient parenteral antimicrobial therapy (OPAT) is a safe and effective alternative to hospitalization for many patients with infectious diseases. The objective of this study was to describe the OPAT experience at a Canadian tertiary academic centre in the absence of a formal OPAT program. This was achieved through a retrospective chart review of OPAT patients discharged from Sunnybrook Health Sciences Centre within a one-year period. Between June 2012 and May 2013, 104 patients (median age 63 years) were discharged home with parenteral antimicrobials. The most commonly treated syndromes included surgical site infections (33%), osteoarticular infections (28%), and bacteremia (21%). The most frequently prescribed antimicrobials were ceftriaxone (21%) and cefazolin (20%). Only 56% of the patients received follow-up care from an infectious diseases specialist. In the 60 days following discharge, 43% of the patients returned to the emergency department, while 26% required readmission. Forty-eight percent of the return visits were due to infection relapse or treatment failure, and 23% could be attributed to OPAT-related complications. These results suggest that many OPAT patients have unplanned health care encounters because of issues related to their infection or treatment, and the creation of a formal OPAT clinic may help improve outcomes. PMID- 27366184 TI - Evidence of Hepatitis B Virus Infection in Cancer and Noncancer Stem Cells Associated with Human Hepatocellular Carcinoma. AB - Both the hepatitis B virus (HBV) and cancer stem cells (CSCs) have been independently implicated in the pathogenesis of hepatocellular carcinoma (HCC). To date, there have been no reports describing HBV infection within CSCs. In this report we describe HBV core (HBcAg) and HBx protein expression within CSCs associated with human HCC. HBV markers were also identified in nonmalignant stem cells present in adjacent nontumor tissue. These findings provide new insights into the pathogenesis of HBV-induced HCC and are potentially relevant to the treatment of both HCC and chronic HBV. PMID- 27366185 TI - Biochemical and Molecular Analysis of Staphylococcus aureus Clinical Isolates from Hospitalized Patients. AB - Staphylococcus aureus is opportunistic human as well as animal pathogen that causes a variety of diseases. A total of 100 Staphylococcus aureus isolates were obtained from clinical samples derived from hospitalized patients. The presumptive Staphylococcus aureus clinical isolates were identified phenotypically by different biochemical tests. Molecular identification was done by PCR using species specific 16S rRNA primer pairs and finally 100 isolates were found to be positive as Staphylococcus aureus. Screened isolates were further analyzed by several microbiological diagnostics tests including gelatin hydrolysis, protease, and lipase tests. It was found that 78%, 81%, and 51% isolates were positive for gelatin hydrolysis, protease, and lipase activities, respectively. Antibiogram analysis of isolated Staphylococcus aureus strains with respect to different antimicrobial agents revealed resistance pattern ranging from 57 to 96%. Our study also shows 70% strains to be MRSA, 54.3% as VRSA, and 54.3% as both MRSA and VRSA. All the identified isolates were subjected to detection of mecA, nuc, and hlb genes and 70%, 84%, and 40% were found to harbour mecA, nuc, and hlb genes, respectively. The current investigation is highly important and informative for the high level multidrug resistant Staphylococcus aureus infections inclusive also of methicillin and vancomycin. PMID- 27366186 TI - Delusional Infestation. AB - Although the practice of infectious diseases involves a broad range of surgical and medical disciplines, interactions with psychiatry are infrequent. Delusional infestation is a condition where an individual has a firmly fixed false belief that they have an infection. Delusional infestation challenges the infectious diseases specialist who must diligently rule out the presence of a true infection. However, perhaps, more importantly, we may need to initiate therapy with neuroleptic medications for which we may have little specific knowledge and experience. In this note we review the diagnosis and management of patients with delusional infestation. PMID- 27366187 TI - Primary Nasal Tuberculosis in a 10-Year-Old Girl. AB - Nasal tuberculosis is a rare clinical entity which mainly presents in elderly people. Nasal tuberculosis has always been considered to be secondary to tuberculosis of the lungs, and in rare instances it is a primary infection, usually when mycobacteria are inhaled. We describe the case of a 10-year-old girl who was successfully treated for primary nasal tuberculosis. This patient is one of the very few children who have been reported to have primary nasal tuberculosis. PMID- 27366188 TI - Plantar Purpura as the Initial Presentation of Viridians Streptococcal Shock Syndrome Secondary to Streptococcus gordonii Bacteremia. AB - Viridians streptococcal shock syndrome is a subtype of toxic shock syndrome. Frequently, the diagnosis is missed initially because the clinical features are nonspecific. However, it is a rapidly progressive disease, manifested by hypotension, rash, palmar desquamation, and acute respiratory distress syndrome within a short period. The disease course is generally fulminant and rarely presents initially as a purpura over the plantar region. We present a case of a 54-year-old female hospital worker diagnosed with viridians streptococcal shock syndrome caused by Streptococcus gordonii. Despite aggressive antibiotic treatment, fluid hydration, and use of inotropes and extracorporeal membrane oxygenation, the patient succumbed to the disease. Early diagnosis of the potentially fatal disease followed by a prompt antibiotic regimen and appropriate use of steroids are cornerstones in the management of this disease to reduce the risk of high morbidity and mortality. PMID- 27366189 TI - Ramsay Hunt Syndrome Associated with Central Nervous System Involvement in an Adult. AB - Ramsay Hunt syndrome associated with varicella zoster virus reactivation affecting the central nervous system is rare. We describe a 55-year-old diabetic female who presented with gait ataxia, right peripheral facial palsy, and painful vesicular lesions involving her right ear. Later, she developed dysmetria, fluctuating diplopia, and dysarthria. Varicella zoster virus was detected in the cerebrospinal fluid by polymerase chain reaction. She was diagnosed with Ramsay Hunt syndrome associated with spread to the central nervous system. Her facial palsy completely resolved within 48 hours of treatment with intravenous acyclovir 10 mg/kg every 8 hours. However, cerebellar symptoms did not improve until a tapering course of steroid therapy was initiated. PMID- 27366190 TI - The impact of contextual family risks on prisoners' children's behavioural outcomes and the potential protective role of family functioning moderators. AB - Research suggests that children of prisoners have an increased risk for behavioural and emotional problems. However, in a resilience approach, one should expect heterogeneous outcomes and thus apply a contextualized perspective. As this is rarely acknowledged in empirical research, the present study sought to fill this gap using data from the Fragile Families and Child Wellbeing study on 801 children of imprisoned fathers. We explored the extent to which cumulative family risks measured during the first year of life (e.g., poverty and mental health problems) predicted behavioural outcomes at age 9 and whether potentially protective aspects of family functioning moderated the impact of these risk factors. Cumulative risk significantly predicted behavioural outcomes, but the associations were weak. No strong evidence of moderation was found. At low risk, mother-child closeness moderated behavioural outcomes. There was also some evidence of moderation by accumulated protective factors. Potential implications for policy and practice and challenges for further research are discussed. PMID- 27366191 TI - Tanreqing Injection Attenuates Lipopolysaccharide-Induced Airway Inflammation through MAPK/NF-kappaB Signaling Pathways in Rats Model. AB - Background. Tanreqing injection (TRQ) is a commonly used herbal patent medicine for treating inflammatory airway diseases in view of its outstanding anti inflammatory properties. In this study, we explored the signaling pathways involved in contributions of TRQ to LPS-induced airway inflammation in rats. Methods/Design. Adult male Sprague Dawley (SD) rats randomly divided into different groups received intratracheal instillation of LPS and/or intraperitoneal injection of TRQ. Bronchoalveolar Lavage Fluid (BALF) and lung samples were collected at 24 h, 48 h, and 96 h after TRQ administration. Protein and mRNA levels of tumor necrosis factor- (TNF-) alpha, Interleukin- (IL-) 1beta, IL-6, and IL-8 in BALF and lung homogenate were observed by ELISA and real-time PCR, respectively. Lung sections were stained for p38 MAPK and NF-kappaB detection by immunohistochemistry. Phospho-p38 MAPK, phosphor-extracellular signal-regulated kinases ERK1/2, phospho-SAPK/JNK, phospho-NF-kappaB p65, phospho IKKalpha/beta, and phospho-IkappaB-alpha were measured by western blot analysis. Results. The results showed that TRQ significantly counteracted LPS-stimulated release of TNF-alpha, IL-1beta, IL-6, and IL-8, attenuated cells influx in BALF, mitigated mucus hypersecretion, suppressed phosphorylation of NF-kappaB p65, IkappaB-alpha, IotaKKalpha/beta, ERK1/2, JNK, and p38 MAPK, and inhibited p38 MAPK and NF-kappaB p65 expression in rat lungs. Conclusions. Results of the current research indicate that TRQ possesses potent exhibitory effects in LPS induced airway inflammation by, at least partially, suppressing the MAPKs and NF kappaB signaling pathways, in a general dose-dependent manner. PMID- 27366192 TI - Icariin Inhibits Pulmonary Hypertension Induced by Monocrotaline through Enhancement of NO/cGMP Signaling Pathway in Rats. AB - It has been reported that icariin (ICA) increased contents of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) by improving expression of endothelial nitric oxide synthase (eNOS) and inhibition of phosphodiesterase type 5 (PDE5). In addition, dysfunction of the NO/cGMP pathway may play a crucial role in the pathogenesis of pulmonary hypertension (PH). In this study, the potential protective effects of ICA on PH induced by monocrotaline (MCT, 50 mg/kg) singly subcutaneous injection were investigated and the possible mechanisms involved in NO/cGMP pathway were explored in male Sprague Dawley rats. The results showed that ICA (20, 40, and 80 mg/kg/d) treatment by intragastric administration could significantly ameliorate PH and upregulate the expression of eNOS gene and downregulate the expression of PDE5 gene in MCT-treated rats. Both ICA (40 mg/kg/d) and L-arginine (200 mg/kg/d), a precursor of NO as positive control, notably increased the contents of NO and cGMP in lung tissue homogenate, which were inversed by treatment with (N) G-nitro-L-arginine-methyl ester (L-NAME), a NOS inhibitor, and L-NAME-treatment could also inhibit the protective effects of ICA (40 mg/kg/d) on mean pulmonary artery pressure and artery remodeling and tends to inhibit right ventricle hypertrophy index. In summary, ICA is effective in protecting against MCT-induced PH in rats through enhancement of NO/cGMP signaling pathway in rats. PMID- 27366193 TI - Untargeted Metabolomics Reveals Intervention Effects of Total Turmeric Extract in a Rat Model of Nonalcoholic Fatty Liver Disease. AB - Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease. Currently, there are no recognized medical therapies effective for NAFLD. Previous studies have demonstrated the effects of total turmeric extract on rats with NAFLD induced by high-fat diet. In this study, serum metabolomics was employed using UHPLC-Q-TOF-MS to elucidate the underlying mechanisms of HFD-induced NAFLD and the therapeutic effects of TE. Supervised orthogonal partial least-squares-discriminant analysis was used to discover differentiating metabolites, and pathway enrichment analysis suggested that TE had powerful combined effects of regulating lipid metabolism by affecting glycerophospholipid metabolism, glycerolipid metabolism, and steroid hormone biosynthesis signaling pathways. In addition, the significant changes in glycerophospholipid metabolism proteins also indicated that glycerophospholipid metabolism might be involved in the therapeutic effect of TE on NAFLD. Our findings not only supply systematic insight into the mechanisms of NAFLD but also provide a theoretical basis for the prevention or treatment of NAFLD. PMID- 27366194 TI - Chinese Herbal Medicine for Functional Abdominal Pain Syndrome: From Clinical Findings to Basic Understandings. AB - Functional abdominal pain syndrome (FAPS) is one of the less common functional gastrointestinal disorders. Conventional therapy has unsatisfactory response to it so people turn to Chinese medicine for help. Currently, we reviewed the whole picture of Chinese herbal medicine (CHM) clinical and basic application in the treatment of FAPS, especially the traditional Chinese medicine (TCM) syndrome, the single herb, and Chinese medicine formulae, thus to provide a solid base to further develop evidence-based study for this common gastrointestinal complaint in the future. We developed the search strategy and set the inclusion and exclusion criteria for article search. From the included articles, we totally retrieved 586 records according to our searching criteria, of which 16 were duplicate records and 291 were excluded for reasons of irrelevance. The full text of 279 articles was retrieved for detailed assessment, of which 123 were excluded for various reasons. The number one used single herb is Radix Ginseng. The most common syndrome was liver qi depression. The most frequently used classic formula was Si-Mo-Tang. This reflected the true situation of clinical practice of Chinese medicine practitioners and could be further systematically synthesized as key points of the therapeutic research for FAPS. PMID- 27366195 TI - Vascular Protective Role of Samul-Tang in HUVECs: Involvement of Nrf2/HO-1 and NO. AB - Samul-Tang (Si-Wu-Tang, SMT), composed of four medicinal herbs, is a well-known herbal formula treating hematological disorder or gynecologic disease. However, vascular protective effects of SMT and its molecular mechanisms on the vascular endothelium, known as the central spot of vascular inflammatory process, are not reported. The aim of this study was to investigate vascular protective effects of SMT water extract in human umbilical vein endothelial cells (HUVECs). Water extract of SMT was prepared and identified by HPLC-PDA analysis. Expression of cell adhesion molecules (CAMs) and heme oxygenase-1 (HO-1) and translocation of nuclear factor-kappa B (NF-kappaB) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were determined by western blot. Nuclear localization of NF-kappaB and Nrf2 was visualized by immunofluorescence and DNA binding activity of NF-kappaB was measured. ROS production, HL-60 monocyte adhesion, and intracellular nitric oxide (NO) were also measured using a fluorescent indicator. SMT suppressed NF kappaB translocation and activation as well as expression of CAMs, monocyte adhesion, and ROS production induced by TNF-alpha in HUVECs. SMT treated HUVECs showed upregulation of HO-1 and NO which are responsible for vascular protective action. Our study suggests that SMT, a traditionally used herbal formula, protects the vascular endothelium from inflammation and might be used as a promising vascular protective drug. PMID- 27366196 TI - Danshen (Salvia miltiorrhiza) Compounds Improve the Biochemical Indices of the Patients with Coronary Heart Disease. AB - Danshen was able to reduce the risk of the patients with coronary heart disease (CHD), but the mechanism is still widely unknown. Biochemical indices (lipid profile, markers of renal and liver function, and homocysteine (Hcy)) are closely associated with CHD risk. We aimed to investigate whether the medicine reduces CHD risk by improving these biochemical indices. The patients received 10 Danshen pills (27 mg/pill) in Dashen group, while the control patients received placebo pills, three times daily. The duration of follow-up was three months. The serum biochemical indices were measured, including lipid profiles (LDL cholesterol (LDL C), HDL-C, total cholesterol (TC), triglycerides (TG), apolipoprotein (Apo) A, ApoB, ApoE, and lipoprotein (a) (Lp(a))); markers of liver function (gamma glutamyl transpeptidase (GGT), total bilirubin (TBil), indirect bilirubin (IBil), and direct bilirubin (DBil)); marker of renal function (uric acid (UA)) and Hcy. After three-month follow-up, Danshen treatment reduced the levels of TG, TC, LDL C, Lp(a), GGT, DBil, UA, and Hcy (P < 0.05). In contrast, the treatment increased the levels of HDL-C, ApoA, ApoB, ApoE, TBil, and IBil (P < 0.05). Conclusion. Danshen can reduce the CHD risk by improving the biochemical indices of CHD patients. PMID- 27366197 TI - Dietary specialization drives multiple independent losses and gains in the bitter taste gene repertoire of Laurasiatherian Mammals. AB - BACKGROUND: Bitter taste perception is essential for species with selective food intake, enabling them to avoid unpalatable or toxic items. Previous studies noted a marked variation in the number of TAS2R genes among various vertebrate species, but the underlying causes are not well understood. Laurasiatherian mammals have highly diversified dietary niche, showing repeated evolution of specialized feeding preferences in multiple lineages and offering a unique chance to investigate how various feeding niches are associated with copy number variation for bitter taste receptor genes. RESULTS: Here we investigated the evolutionary trajectories of TAS2Rs and their implications on bitter taste perception in whole genome assemblies of 41 Laurasiatherian species. The number of intact TAS2Rs copies varied considerably, ranging from 0 to 52. As an extreme example of a narrow dietary niche, the Chinese pangolin possessed the lowest number of intact TAS2Rs (n = 2) among studied terrestrial vertebrates. Marine mammals (cetacea and pinnipedia), which swallow prey whole, presented a reduced copy number of TAS2Rs (n = 0-5). In contrast, independent insectivorous lineages, such as the shrew and insectivorous bats possessed a higher TAS2R diversity (n = 52 and n = 20-32, respectively), exceeding that in herbivores (n = 9-22) and omnivores (n = 18-22). CONCLUSIONS: Besides herbivores, insectivores in Laurasiatheria tend to have more functional TAS2Rs in comparison to carnivores and omnivores. Furthermore, animals swallowing food whole (cetacean, pinnipedia and pangolin) have lost most functional TAS2Rs. These findings provide the most comprehensive view of the bitter taste gene repertoire in Laurasiatherian mammals to date, casting new light on the relationship between losses and gains of TAS2Rs and dietary specialization in mammals. PMID- 27366198 TI - Levy patterns in seabirds are multifaceted describing both spatial and temporal patterning. AB - BACKGROUND: The flight patterns of albatrosses and shearwaters have become a touchstone for much of Levy flight research, spawning an extensive field of enquiry. There is now compelling evidence that the flight patterns of these seabirds would have been appreciated by Paul Levy, the mathematician after whom Levy flights are named. Here we show that Levy patterns (here taken to mean spatial or temporal patterns characterized by distributions with power-law tails) are, in fact, multifaceted in shearwaters being evident in both spatial and temporal patterns of activity. RESULTS: We tested for Levy patterns in the at-sea behaviours of two species of shearwater breeding in the North Atlantic Ocean (Calonectris borealis) and the Mediterranean sea (C. diomedea) during their incubating and chick-provisioning periods. We found that distributions of flight durations, on/in water durations and inter-dive time-intervals have power-law tails and so bear the hallmarks of Levy patterns. CONCLUSIONS: The occurrence of these statistical laws is remarkable given that bird behaviours are strongly shaped by an individual's motivational state and by complex environmental interactions. Our observations could take Levy patterns as models of animal behaviour to a new level by going beyond the characterisation of spatial movements to characterise how different behaviours are interwoven throughout daily animal life. PMID- 27366199 TI - Evolution of body morphology and beak shape revealed by a morphometric analysis of 14 Paridae species. AB - BACKGROUND: Morphological characters of birds reflect their adaptive evolution and ecological requirements and are also relevant to phylogenetic relationships within a group of related species. The tits (Paridae) are known to be outwardly homogeneous in shape, with one aberrant member, the Ground Tit (Pseudopodoces humilis), which is quite different from its relatives in both body morphology and beak shape. We combined traditional measurements and geometric morphometrics to quantify the variation in body morphology and beak shape of 14 Paridae species distributed in China. Based on these results, we sought to assess the contribution of phylogeny, altitude and species interactions to the evolution of morphological traits. RESULTS: The basic features for discriminating among the 14 species studied here were overall body size, the ratio of body and tail length to culmen and tarsus length, and beak shape (long/slender/pointy vs. short/robust/blunt). These dimensions clearly separate Ps. humilis and Melanochlora sultanea from the other species in shape space. Body length and PC3 of beak shape (round outline vs. straight outline) show significant phylogenetic signals. Across 14 species, altitude is related to tarsus, culmen length and PC1 of beak shape. Within Parus major, altitude is related to body weight, body length, culmen length and PC1 of body morphology. Morphological distances and geographic distances among species are positively correlated. CONCLUSIONS: The body morphology of Paridae species shows extensive evolutionary changes, while their beak has mainly evolved along the long/slender/pointy vs. short/robust/blunt dimension. Only body length and beak curvature show a phylogenetic signal. Altitude correlates with multiple traits both across and within species, suggesting that altitude is an important factor in promoting morphological divergence. The deviant appearance of Ps. humilis corresponds to its foraging and feeding adaptations to high-altitude steppe habitats. Our results also show a higher level of morphological divergence with greater difference in distribution ranges among the Paridae species involved in this study. PMID- 27366200 TI - Resveratrol improves glycemic control in insulin-treated diabetic rats: participation of the hepatic territory. AB - BACKGROUND: Resveratrol is a natural polyphenol that has been proposed to improve glycemic control in diabetes, by mechanisms that involve improvement in insulin secretion and activity. In type 1 diabetes (T1D), in which insulin therapy is obligatory, resveratrol treatment has never been investigated. The present study aimed to evaluate resveratrol as an adjunctive agent to insulin therapy in a T1D like experimental model. METHODS: Rats were rendered diabetic by streptozotocin (STZ) treatment. Twenty days later, four groups of animals were studied: non diabetic (ND); diabetic treated with placebo (DP); diabetic treated with insulin (DI) and diabetic treated with insulin plus resveratrol (DIR). After 30 days of treatment, 24-hour urine was collected; then, blood, soleus muscle, proximal small intestine, renal cortex and liver were sampled. Specific glucose transporter proteins were analyzed (Western blotting) in each territory of interest. Solute carrier family 2 member 2 (Slc2a2), phosphoenolpyruvate carboxykinase (Pck1) and glucose-6-phosphatase catalytic subunit (G6pc) mRNAs (qPCR), glycogen storage and sirtuin 1 (SIRT1) activity were analyzed in liver. RESULTS: Diabetes induction increased blood glucose, plasma fructosamine concentrations, and glycosuria. Insulin therapy partially recovered the glycemic control; however, resveratrol as adjunctive therapy additionally improved glycemic control and restored plasma fructosamine concentration to values of non diabetic rats. Resveratrol did not alter the expression of the glucose transporters GLUT2 and SGLT1 in the intestine, GLUT2 and SGLT2 in kidney and GLUT4 in soleus, suggesting that fluxes of glucose in these territories were unaltered. Differently, in liver, resveratrol promoted a reduction in Slc2a2, Pck1, and G6pc mRNAs, as well as in GLUT2 protein (P < 0.05, DIR vs. DI); besides, it increased (P < 0.01, DIR vs. DI) the hepatic glycogen content, and SIRT1 protein. CONCLUSIONS: Resveratrol is able to improve glycemic control in insulin-treated T1D-like rats. This effect seems not to involve changes in glucose fluxes in the small intestine, renal proximal tubule, and soleus skeletal muscle; but to be related to several changes in the liver, where downregulation of Slc2a2/GLUT2, Pck1, and G6pc expression was observed, favoring reduction of glucose production and efflux. Besides, resveratrol increased SIRT1 nuclear protein content in liver, which may be related to the observed gene expression regulations. PMID- 27366201 TI - Ultrasmall dopamine-coated nanogolds: preparation, characteristics, and CT imaging. AB - Water-dispersible ultrasmall nanogolds (WDU AuNPs) and their dopamine-coated nanogolds (WDU AuNPs@DPAs) were prepared by a reduction method with sodium borohydride as a reducing agent and a stabilised agent of 2-mercaptosuccinic acid in aqueous solution. The effects of these nanoparticles on computed tomography (CT) imaging were evaluated. The size distributions and Zeta potential of the nanoparticles were measured with a Malvern size analyser, and nanoparticle morphology was observed by transmission electron microscopy. These characteristics were confirmed by Fourier transform spectroscopy and ultraviolet/visible spectra. It was found that WDU AuNPs@DPAs were 5.4 nm in size with clear core-shell structure. The 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5 diphenyltetrazolium bromide assay results showed that the WDU AuNPs and WDU AuNPs@DPAs were hypotoxic to different cells. The WDU AuNPs@DPAs showed a much longer circulation time and a larger CT attenuation coefficient than iohexol and could be excreted by the kidney and bladder. These nanoparticles showed considerable potential for future application in CT imaging. PMID- 27366202 TI - Towards Identify Selective Antibacterial Peptides Based on Abstracts Meaning. AB - We present an Identify Selective Antibacterial Peptides (ISAP) approach based on abstracts meaning. Laboratories and researchers have significantly increased the report of their discoveries related to antibacterial peptides in primary publications. It is important to find antibacterial peptides that have been reported in primary publications because they can produce antibiotics of different generations that attack and destroy the bacteria. Unfortunately, researchers used heterogeneous forms of natural language to describe their discoveries (sometimes without the sequence of the peptides). Thus, we propose that learning the words meaning instead of the antibacterial peptides sequence is possible to identify and predict antibacterial peptides reported in the PubMed engine. The ISAP approach consists of two stages: training and discovering. ISAP founds that the 35% of the abstracts sample had antibacterial peptides and we tested in the updated Antimicrobial Peptide Database 2 (APD2). ISAP predicted that 45% of the abstracts had antibacterial peptides. That is, ISAP found that 810 antibacterial peptides were not classified like that, so they are not reported in APD2. As a result, this new search tool would complement the APD2 with a set of peptides that are candidates to be antibacterial. Finally, 20% of the abstracts were not semantic related to APD2. PMID- 27366203 TI - Synergistic effects of melphalan and Pinus kesiya Royle ex Gordon (Simaosong) extracts on apoptosis induction in human cancer cells. AB - BACKGROUND: This study aims to determine the synergistic effects of the chemotherapeutic drug melphalan and the phytoconstituents extracted from Pinus kesiya Royle ex Gordon (Simaosong) in human cancer cells. METHODS: P. kesiya twigs extracted from 50 % ethanol-water were evaluated alone (6-500 ug/mL) and in combination with melphalan (0.75-15 ug/mL). The cytotoxic effects of single extract or extract and melphalan combination were examined by a neutral red assay to investigate their antiproliferative and apoptosis induction effects in the U937 and HepG2 cell lines. Nuclei morphological change and DNA fragmentation were examined by DNA nuclei staining with 4'6-diamidino-2-phenylindole (DAPI) and agarose gel electrophoresis, respectively. The chemical constituents of the P. kesiya extract were assessed using gas chromatography-mass spectrometry (GC-MS) analysis. The synergistic effects of different IC50 ratios of the P. kesiya extract and melphalan combination were analyzed in each cancer cell line. The dose reduction index (DRI) was calculated to determine the extent of concentration reduction in the combination treatment compared with the concentration of each single treatment. RESULTS: The IC50 ratios for melphalan to P. kesiya extract that caused 75 % antiproliferation could be reduced after combination. This response was greater in the U937 cells than in the HepG2 cells (all P < 0.001). Melphalan and P. kesiya extract had a similar effect on apoptosis induction both singly and in combination. P. kesiya extract synergized the antiproliferation and apoptosis induction effects of melphalan. CONCLUSIONS: Combining the P. kesiya extract with melphalan reduced toxicity while retaining the therapeutic efficacy of melphalan. PMID- 27366204 TI - The pattern of prognostic and risk indicators among women with breast cancer undergoing modified radical mastectomy in Dar es Salaam, Tanzania. AB - BACKGROUND: Breast cancer is the commonest female malignancy globally and the second (after uterine cervix) in sub-Saharan Africa including Tanzania. Prognostic indicators reportedly influence post-mastectomy adjuvant therapy by predicting risks on survival and recurrence although in Tanzania this data is lacking. Here, we evaluate the pattern of prognostic and risk indicators among women with breast cancer undergoing modified-radical-mastectomy (MRM) at Muhimbili National Hospital (MNH) and Tumaini Hospital (TH), Dar es Salaam, Tanzania. METHODS: This hospital-based prospective cross-sectional study included female patients undergoing MRM from April 2011 to January 2012. Clinical stage I III patients were enrolled after being scheduled for mastectomy. Patients with evidence of distant metastasis (stage IV) were excluded. Mastectomy and axillary lymph nodes biopsies were submitted to the Histopathology laboratory for grade, type, nodal and margins status. Data was collected using a structured questionnaire and analyzed using SPSS. RESULTS: A total of 348 patients were admitted with breast cancer including 86 patients (with 16 from TH having similar demography and presentation) meeting inclusion criteria. Age-range at diagnosis was 28-79 years, mean 52.1 years. Most (89 %) attained menarche after 11 years. About 56 % were postmenopausal. The majority (78 %) were multiparous with positive family history in 14.1 and 37.6 % used hormonal contraceptives. About 27.1 % were social alcohol drinkers. The majority (61 %) had T4b disease, 75.6 % had positive axillary nodes including 42.7 % with 4-9 involved nodes (N2). The commonest (91.9 %) histological type was invasive ductal carcinoma. Lobular, medullary and mucinous carcinomas were rare. Most (83.7 %) of our patients presented with stage III and the rest stage II. Intermediate- and high-grade tumors accounted for 73.5 %. Following MRM, 25 % of our patients had positive surgical margins and similarly for the base. CONCLUSIONS: Most of our breast cancer patients present with frequent risks including younger age, multiparity, hormonal contraceptives use, alcohol use and family history. Unfavourable prognostic indicators including late stages, large primary tumor size, skin infiltration, positive surgical margins, positive axillary lymph nodes and a high histological grade were associated. A sustainable screening program by self examination to allow early diagnosis is needed to reduce morbidity and mortality from this cancer. PMID- 27366205 TI - Do school teachers and primary contacts in residential youth care institutions recognize mental health problems in adolescents? AB - BACKGROUND: Studies show that adolescents living in residential youth care (RYC) institutions experience more mental health problems than others. This paper studies how well teachers and primary contacts in RYC institutions recognize adolescents' mental health problems as classified by The Child and Adolescent Psychiatric Assessment diagnostic interviews (CAPA). METHODS: All residents between 12 and 23 years of age living in RYC institutions in Norway and enrolled in school at the time of data collection were invited to participate in the study. Of the 601 available children, 400 participated in the study, namely 230 girls, mean age = 16.9 years, SD = 1.2 and 170 boys, mean age = 16.5 years, SD = 1.5. The Child Behavior Checklist (CBCL) and Teacher's Report Form (TRF) were used. The sensitivity and specificity of these instruments were studied. RESULTS: We observed a significant gap between the mental health problems diagnosed by the CAPA interviews and the problems reported by primary contacts on the CBCL and by teachers on the TRF. The CBCL showed a higher sensitivity than the TRF, whereas the TRF showed a higher specificity than the CBCL. Both primary contacts and teachers classified externalizing problems fairly well such as ADHD in both genders and conduct disorder in girls. Both teachers and primary contacts, however, had more problems detecting internalizing problems. Teachers may have a tendency to view most students as healthy and to underestimate the severity of their problems, whereas primary contacts may tend to overestimate the number of problems and view adolescents as sicker than they really are. CONCLUSION: The Child Welfare System should revise their intake procedures to detect possible problems early on and to introduce the necessary treatment. It is important to identify factors that increase healthy school adaption in order for these adolescents to accomplish school in a proper way since education is important for a successful adult life. PMID- 27366206 TI - Natural diversity of cellulases, xylanases, and chitinases in bacteria. AB - BACKGROUND: Glycoside hydrolases (GH) targeting cellulose, xylan, and chitin are common in the bacterial genomes that have been sequenced. Little is known, however, about the architecture of multi-domain and multi-activity glycoside hydrolases. In these enzymes, combined catalytic domains act synergistically and thus display overall improved catalytic efficiency, making these proteins of high interest for the biofuel technology industry. RESULTS: Here, we identify the domain organization in 40,946 proteins targeting cellulose, xylan, and chitin derived from 11,953 sequenced bacterial genomes. These bacteria are known to be capable, or to have the potential, to degrade polysaccharides, or are newly identified potential degraders (e.g., Actinospica, Hamadaea, Cystobacter, and Microbispora). Most of the proteins we identified contain a single catalytic domain that is frequently associated with an accessory non-catalytic domain. Regarding multi-domain proteins, we found that many bacterial strains have unique GH protein architectures and that the overall protein organization is not conserved across most genera. We identified 217 multi-activity proteins with at least two GH domains for cellulose, xylan, and chitin. Of these proteins, 211 have GH domains targeting similar or associated substrates (i.e., cellulose and xylan), whereas only six proteins target both cellulose and chitin. Fifty-two percent of multi-activity GHs are hetero-GHs. Finally, GH6, -10, -44 and -48 domains were mostly C-terminal; GH9, -11, -12, and -18 were mostly N-terminal; and GH5 domains were either N- or C-terminal. CONCLUSION: We identified 40,946 multi-domain/multi-activity proteins targeting cellulase, chitinase, and xylanase in bacterial genomes and proposed new candidate lineages and protein architectures for carbohydrate processing that may play a role in biofuel production. PMID- 27366207 TI - Microbial synthesis of poly-gamma-glutamic acid: current progress, challenges, and future perspectives. AB - Poly-gamma-glutamic acid (gamma-PGA) is a naturally occurring biopolymer made from repeating units of l-glutamic acid, d-glutamic acid, or both. Since some bacteria are capable of vigorous gamma-PGA biosynthesis from renewable biomass, gamma-PGA is considered a promising bio-based chemical and is already widely used in the food, medical, and wastewater industries due to its biodegradable, non toxic, and non-immunogenic properties. In this review, we consider the properties, biosynthetic pathway, production strategies, and applications of gamma-PGA. Microbial biosynthesis of gamma-PGA and the molecular mechanisms regulating production are covered in particular detail. Genetic engineering and optimization of the growth medium, process control, and downstream processing have proved to be effective strategies for lowering the cost of production, as well as manipulating the molecular mass and conformational/enantiomeric properties that facilitate screening of competitive gamma-PGA producers. Finally, future prospects of microbial gamma-PGA production are discussed in light of recent progress, challenges, and trends in this field. PMID- 27366208 TI - Matrix and cell phenotype differences in Dupuytren's disease. AB - BACKGROUND: Dupuytren's disease is a fibroproliferative disease of the hand and fingers, which usually manifests as two different phenotypes within the same patient. The disease first causes a nodule in the palm of the hand, while later, a cord develops, causing contracture of the fingers. RESULTS: We set out to characterize the two phenotypes by comparing matched cord and nodule tissue from ten Dupuytren's patients. We found that nodule tissue contained more proliferating cells, CD68-positive macrophages and alpha-smooth muscle actin (alpha-SMA)-positive myofibroblastic cells. qPCR analysis showed an increased expression of COL1A1, COL1A2, COL5A1, and COL6A1 in nodule tissue compared to cord tissue. Immunohistochemistry showed less deposition of collagen type I in nodules, although they contained more fibronectin, collagen type V, and procollagen 1. Lower collagen levels in nodule were confirmed by HPLC measurements of the Hyp/Pro ratio. PCOLCE2, an activator of BMP1, the main enzyme cleaving the C-terminal pro-peptide from procollagen, was also reduced in nodule. Cord tissue not only contained more collagen I, but also higher levels of hydroxylysylpyridinoline and lysylpyridinoline residues per triple helix, indicating more crosslinks. CONCLUSIONS: Our results clearly show that in Dupuytren's disease, the nodule is the active disease unit, although it does not have the highest collagen protein levels. The difference in collagen type I deposition compared to mRNA levels and procollagen 1 levels may be connected to a decrease in procollagen processing. PMID- 27366209 TI - Recurrent amplification of RTEL1 and ABCA13 and its synergistic effect associated with clinicopathological data of gastric adenocarcinoma. AB - BACKGROUND: Despite progression in treatment of gastric cancer, prognosis of patients remains poor, in part due to the low rate of diagnosis during its early stages. This paradigm implies the necessity to identify molecular biomarkers for early gastric cancer diagnosis, as well as for disease monitoring, thus contributing to the development of new therapeutic approaches. In a previous study, performed by array-Comparative Genomic Hybridization, we described for the first time in literature recurrent amplification of RTEL1 and ABCA13 genes in gastric cancer. Thus, the aim of the present study was to validate recurrent amplification of RTEL1 and ABCA13 genes and associate CNV status with clinicopathological data. FINDINGS: Results showed RTEL1 and ABCA13 amplification in 38 % of samples. Statistical analysis demonstrated that RTEL amplification is more common in older patients and more associated with intestinal type and ABCA13 amplification increases the risk of lymph node metastasis and is more common in men. Co-amplification of these genes showed a significant association with advanced staging. CONCLUSIONS: aCGH is a very useful tool for investigating novel genes associated with carcinogenesis and RTEL1 amplification may be important for the development of gastric cancer in older patients, besides being a probable event contributing for chromosomal instability in intestinal gastric carcinogenesis. ABCA13 amplification may have age-specific function and could be considered a useful marker for predicting lymph node metastasis in resected gastric cancer patients in early stage. Lastly, RTEL1 and ABCA13 synergistic effect may be considered as a putative marker for advanced staging in gastric cancer patients. PMID- 27366210 TI - Principal component analysis based unsupervised feature extraction applied to budding yeast temporally periodic gene expression. AB - BACKGROUND: The recently proposed principal component analysis (PCA) based unsupervised feature extraction (FE) has successfully been applied to various bioinformatics problems ranging from biomarker identification to the screening of disease causing genes using gene expression/epigenetic profiles. However, the conditions required for its successful use and the mechanisms involved in how it outperforms other supervised methods is unknown, because PCA based unsupervised FE has only been applied to challenging (i.e. not well known) problems. RESULTS: In this study, PCA based unsupervised FE was applied to an extensively studied organism, i.e., budding yeast. When applied to two gene expression profiles expected to be temporally periodic, yeast metabolic cycle (YMC) and yeast cell division cycle (YCDC), PCA based unsupervised FE outperformed simple but powerful conventional methods, with sinusoidal fitting with regards to several aspects: (i) feasible biological term enrichment without assuming periodicity for YMC; (ii) identification of periodic profiles whose period was half as long as the cell division cycle for YMC; and (iii) the identification of no more than 37 genes associated with the enrichment of biological terms related to cell division cycle for the integrated analysis of seven YCDC profiles, for which sinusoidal fittings failed. The explantation for differences between methods used and the necessary conditions required were determined by comparing PCA based unsupervised FE with fittings to various periodic (artificial, thus pre-defined) profiles. Furthermore, four popular unsupervised clustering algorithms applied to YMC were not as successful as PCA based unsupervised FE. CONCLUSIONS: PCA based unsupervised FE is a useful and effective unsupervised method to investigate YMC and YCDC. This study identified why the unsupervised method without pre-judged criteria outperformed supervised methods requiring human defined criteria. PMID- 27366211 TI - Neoadjuvant therapy for pancreatic cancer: an ongoing debate. PMID- 27366212 TI - Systematic review: third-line susceptibility-guided treatment for Helicobacter pylori infection. AB - BACKGROUND: Susceptibility-guided therapies (SGTs) have been proposed as preferable to empirical rescue treatments after two treatment failures. The aim of this study was to perform a systematic review and meta-analysis evaluating the effectiveness and efficacy of SGT as third-line therapy. METHODS: A systematic search was performed in multiple databases. Studies reporting cure rates of Helicobacter pylori with SGT in third-line therapy were selected. A qualitative analysis describing the current evidence and a pooled mean analysis summarizing the cure rates of SGT in third-line therapy was performed. RESULTS: No randomized controlled trials or comparative studies were found. Four observational studies reported cure rates with SGT in third-line treatment, and three studies which mixed patients with second- and third-line treatment also reported cure rates with SGT. The majority of the studies included the patients when culture had been already obtained, and so the effectiveness of SGT and empirical therapy has never been compared. A pooled mean analysis including four observational studies (283 patients) showed intention-to-treat and per-protocol eradication rates with SGT of 72% (95% confidence interval 56-87%; I(2) : 92%) and 80% (95% confidence interval 71-90%; I(2) : 80%), respectively. CONCLUSIONS: SGT may be an acceptable option as rescue treatment. However, cure rates are, at best, moderate and this approach has never been compared with a well-devised empirical therapy. The evidence in favor of SGT as rescue therapy is currently insufficient to recommend its use. PMID- 27366213 TI - Low-dose azathioprine is effective in maintaining remission in steroid-dependent ulcerative colitis: results from a territory-wide Chinese population-based IBD registry. AB - BACKGROUND: Whether low-dose azathioprine (AZA) is effective in maintaining remission in patients with steroid-dependent ulcerative colitis (UC) remains unclear. We assessed the efficacy and safety of low-dose AZA in a Chinese population with UC. METHODS: We identified steroid-dependent UC patients in clinical remission on AZA maintenance therapy from a territory-wide IBD Registry. Standard- and low-dose AZA were defined as at least 2 mg/kg/day and less than 2 mg/kg/day, respectively. Relapse rates were analyzed by Kaplan-Meier analysis and compared using log-rank test. RESULTS: Among 1226 UC patients, 128 (53% male, median duration on AZA 44 months) were included. Median maintenance AZA dose was 1.3 mg/kg/day. 97.7% of the patients were on concomitant oral 5-aminosalicylic acid. Cumulative relapse-free rates in patients on standard-dose and low-dose AZA were 71.2%, 52.8% and 45.2%, and 71.8%, 55.3% and 46.2% at 12, 24 and 36 months, respectively (p = 0.871). Relapse rate within 12 months was higher in patients who withdrew compared with those who maintained on AZA (52.6% versus 29.4%; p = 0.045). Mean corpuscular volume increased after AZA therapy in both of the low dose [median (interquartile range, IQR): 88.2 (81.4-92.2) versus 95.1 (90.1 100.9) fl, p < 0.001] and standard-dose subgroups [median (IQR) 86.8 (76.9-89.9) versus 94.7 (85.9-99.7) fl, p < 0.001]. Leukopenia occurred in 21.1% of the patients. Patients on standard dose had a higher risk for leukopenia than those on low-dose AZA [odds ratio (OR) 3.9, 95% CI 1.9-8.2, p < 0.001]. CONCLUSIONS: In the Chinese population, low-dose AZA is effective for maintaining remission in steroid-dependent UC patients. Standard-dose AZA was associated with more than threefold increased risk of leukopenia. PMID- 27366214 TI - Ipilimumab-induced colitis: experience from a tertiary referral center. AB - BACKGROUND: Ipilimumab is an anticytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody used for the treatment of malignant melanoma. It can cause immune-mediated inflammatory adverse events, including diarrhoea and even intestinal perforation or death in clinical trials but there is a dearth of data on postmarketing outcomes. METHODS: A total of 546 patients attending for treatment of metastatic melanoma between 1 January 2009 and 31 August 2015 were identified by interrogation of the oncology database. A total of 83 of these patients received ipilimumab. Clinical information was extracted from chart reviews, endoscopy and radiology reports, and prescription data. RESULTS: A total of 83 patients received ipilimumab. Only 19.3% (n = 16) of patients developed a diarrhoeal illness not attributable to other causes. The median grade of diarrhoea among included patients was 2 (range 1-4). In two cases, diarrhoea settled spontaneously without any specific treatment. A total of 87.5% of patients received antidiarrhoeal agents such as loperamide or codeine. These resolved symptoms in all patients with grade 1 diarrhoea. For other treatment, 50% patients received systemic glucocorticosteroids and 31.3% required infliximab. Infliximab resolved symptoms in 100% of cases compared with 50% for systemic glucocorticosteroids. CONCLUSIONS: The rate of diarrhoea related to ipilimumab in real-world practice is substantial, but below the range observed in data from RCTs. Grade 1 colitis can usually be managed symptomatically, without recourse to stopping ipilimumab. When diarrhoea was grade 2 or above, results from glucocorticosteroids use proved disappointing; but infliximab has been shown to work well. Further research is required into the earlier use of infliximab as an effective treatment for ipilimumab-induced diarrhoea. PMID- 27366216 TI - Cost-effectiveness analysis of rifaximin-alpha administration for the reduction of episodes of overt hepatic encephalopathy in recurrence compared with standard treatment in France. AB - BACKGROUND: Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that occurs most often in a context of acute or chronic liver disease. Despite the seriousness of the pathology, only a few treatments have been developed for improving its management. Rifaximin-alpha is the first treatment that has been clinically developed for overt HE (OHE) episodes. Recent results of clinical studies demonstrated its significant improvement in the health-related quality of life. The objective of the current study was to estimate the long-term cost effectiveness of rifaximin-alpha used in combination with lactulose compared with lactulose monotherapy in cirrhotic patients, who have experienced at least two prior OHE events. METHODS: A Markov model was used to estimate rifaximin-alpha cost-effectiveness, evaluating it from the perspective of all contributors as recommended by French health technology assessment guidelines. Costs were based on current French treatment practices. The transition between health states was based on the reanalysis of the rifaximin-alpha pivotal clinical trials RFHE3001 and RFHE3002. The main outcome of the model was cost per quality adjusted life year (QALY). RESULTS: The results indicate that rifaximin-alpha is a cost effective treatment option with an incremental cost per QALY gained of ?19,187 and ?18,517 over two different time horizons (2 and 5 years). The robustness of the model was studied using probabilistic sensitivity analysis. CONCLUSION: For the societal willingness to pay threshold of ?27,000 per QALY gained, rifaximin alpha in combination with lactulose is a cost-effective and affordable treatment for patients who have experienced at least two prior overt HE episodes. PMID- 27366215 TI - Probiotics modify tight-junction proteins in an animal model of nonalcoholic fatty liver disease. AB - BACKGROUND: We have investigated the effects of a multispecies probiotic preparation containing a combination of probiotic bacterial genera that included Bifidobacteria, Lactobacilli and a Streptococcus in a mouse model of high-fat diet or obesity-induced liver steatosis. METHODS: Three groups of C57B1/6J mice were fed either a standard chow or a high-fat diet for 20 weeks, while a third group was fed a high-fat diet for 10 weeks and then concomitantly administered probiotics for a further 10 weeks. Serum, liver and large bowel samples were collected for analysis. RESULTS: The expression of the tight-junction proteins ZO 1 and ZO-2 was reduced (p < 0.05) in high-fat diet-fed mice compared to chow-fed mice. Probiotic supplementation helped to maintain tight ZO-1 and ZO-2 expression compared with the high-fat diet group (p < 0.05), but did not restore ZO-1 or ZO 2 expression compared with chow-fed mice. Mice fed a high-fat diet +/- probiotics had significant steatosis development compared with chow-fed mice (p < 0.05); steatosis was less severe in the probiotics group compared with the high-fat diet group. Hepatic triglyceride concentration was higher in mice fed a high-fat diet +/- probiotics compared with the chow group (p < 0.05), and was lower in the probiotics group compared with the high-fat diet group (p < 0.05). Compared with chow-fed mice, serum glucose, cholesterol concentration and the activity of alanine transaminase were higher (p < 0.05), whereas serum triglyceride concentration was lower (p < 0.05) in mice fed a high-fat diet +/- probiotics. CONCLUSIONS: Supplementation with a multispecies probiotic formulation helped to maintain tight-junction proteins ZO-1 and ZO-2, and reduced hepatic triglyceride concentration compared with a high-fat diet alone. PMID- 27366217 TI - Predictors of pain response in patients undergoing endoscopic ultrasound-guided neurolysis for abdominal pain caused by pancreatic cancer. AB - BACKGROUND: Interventional endoscopic ultrasound (EUS)-guided procedures such as EUS-guided celiac ganglia neurolysis (EUS-CGN) and EUS-guided broad plexus neurolysis (EUS-BPN) were developed to treat abdominal cancer-associated pain; however, these procedures are not always effective. The aim of this study was to explore predictors of pain response in EUS-guided neurolysis for pancreatic cancer-associated pain. METHODS: This was a retrospective analysis of prospectively collected data of 112 consecutive patients who underwent EUS-BPN in our institution. EUS-CGN was added in cases of visible celiac ganglia. The neurolytic-spread area was divided into six sections and evaluated by post procedural computed tomography scanning. Pain intensity was assessed using a visual analog scale (VAS), and a decrease in VAS scores by ?3 points after neurolysis was considered a good pain response. Univariable and multivariable logistic regression analyses were performed to explore predictors of pain response at 1 and 4 weeks, and complications. RESULTS: A good pain response was obtained in 77.7% and 67.9% of patients at 1 and 4 weeks, respectively. In the multivariable analysis of these patients, the combination method (EUS-BPN plus CGN) was a significant positive predictive factor at 1 week (odds ratio = 3.69, p = 0.017) and 4 weeks (odds ratio = 6.37, p = 0.043). The numbers of neurolytic/contrast spread areas (mean +/- SD) were 4.98 +/- 1.08 and 4.15 +/- 1.12 in patients treated with the combination method and single method, respectively (p < 0.001). There was no significant predictor of complications. CONCLUSIONS: EUS-BPN in combination with EUS-CGN was a predictor of a good pain response in EUS-guided neurolysis for pancreatic cancer-related pain. The larger number of neurolytic/contrast spread areas may lead to better outcomes in patients receiving combination treatment. PMID- 27366218 TI - The association between socioeconomic status and the symptoms at diagnosis of celiac disease: a retrospective cohort study. AB - BACKGROUND: There are little data on patient factors that impact diagnosis rates of celiac disease. This study aims to evaluate the association between patient socioeconomic status and the symptoms at diagnosis of celiac disease. METHODS: A total of 872 patients with biopsy-proven celiac disease were categorized based on the presence or absence of (1) diarrhea and (2) any gastrointestinal symptoms at diagnosis. Univariate and multivariate analyses were used to assess the association between socioeconomic status and symptoms. RESULTS: Patients without diarrhea at presentation had a higher mean per capita income (US$34,469 versus US$32,237, p = 0.02), and patients without any gastrointestinal symptoms had a higher mean per capita income (US$36,738 versus US$31,758, p < 0.01) compared with patients having such symptoms. On multivariable analysis adjusting for sex, age, autoimmune or psychiatric comorbidities, and income, per capita income remained a significant predictor of diagnosis without gastrointestinal symptoms (odds ratio: 1.71, 95% confidence interval: 1.17-2.50, p < 0.01), and it showed a trend towards significance in diagnosis without diarrhea (odds ratio: 1.40, 95% confidence interval: 0.98-2.02, p = 0.06). CONCLUSIONS: Patients with nonclassical symptoms of celiac disease are less likely to be diagnosed if they are of lower socioeconomic status. Celiac disease may be under-recognized in this population due to socioeconomic factors that possibly include lower rates of health-seeking behavior and access to healthcare. PMID- 27366219 TI - The clinical potential of etrolizumab in ulcerative colitis: hypes and hopes. AB - Antiadhesion molecules are effective and safe in patients with ulcerative colitis (UC). Etrolizumab, a monoclonal antibody targeting both alpha4beta7 and alphaEbeta7, represents a promising therapy for patients with UC, since this novel mechanism of action may be effective in blocking leukocyte recruitment both at the vascular and at the mucosal level. Preliminary studies show that etrolizumab is effective in inducing clinical response and remission, and mucosal healing. Moreover, new predictors of response have recently been identified, opening the way to a tailored therapeutic approach. This review of the literature aims to present and discuss the most recent evidence on etrolizumab in UC, focusing on the clinical implications of the use of etrolizumab in UC. PMID- 27366220 TI - Predicting durable response or resistance to antitumor necrosis factor therapy in inflammatory bowel disease. AB - Monoclonal antibodies to tumor necrosis factor (TNF) have become a mainstay of the therapeutic armamentarium in inflammatory bowel disease (IBD) over the last 15 years. Although highly effective, primary and secondary nonresponse are common and associated with poor clinical outcomes and significant costs. Multiple clinical, genetic and immunopharmacological factors may impact the response to anti-TNFs. Early stratification of IBD patients by the expected risk of therapeutic failure during the induction and maintenance phases of treatment may allow for treatment optimization and potentially optimal short- and long-term outcomes. The aim of this review is to summarize the current data concerning the potential predictors of therapeutic success and failure of anti-TNFs in IBD. PMID- 27366221 TI - Mongersen, an oral Smad7 antisense oligonucleotide, in patients with active Crohn's disease. AB - In Crohn's disease (CD), the tissue-damaging inflammation is sustained by defects of counter-regulatory mechanisms, which normally inhibit immune-inflammatory signals and promote repair of mucosal injury. In particular, in inflamed gut of CD patients there are elevated levels of Smad7, an intracellular protein that inhibits the function of transforming growth factor (TGF)-beta1. Knockdown of Smad7 with a specific antisense oligonucleotide, named mongersen, restores TGF beta1 activity thus leading to suppression of inflammatory pathways and resolution of colitis in mice. Consistently, oral administration of mongersen to patients with active CD induces clinical remission. In this article, we review the available data supporting the pathogenic role of Smad7 in CD and discuss the results of recent phase I and II trials assessing the efficacy and safety of mongersen in CD patients. PMID- 27366222 TI - Stem cell-based therapies in inflammatory bowel disease: promises and pitfalls. AB - Inflammatory bowel disease (IBD) is a chronic, often relapsing, condition that deeply impacts the quality of life for many patients. Although there have been significant advances in medical treatments, a large proportion of patients become refractory to available therapeutic options. Stem-cell therapy through hematopoietic stem cells (HSCs) or mesenchymal stem (stromal) cells (MSCs) is a promising therapeutic option for severe refractory cases especially when surgery is not feasible. In HSC transplantation, the objective is to destroy the 'autoreactive' immune cells responsible for disease chronicity, and to re establish gut tolerance to gut microbes. In perianal Crohn's disease (CD), the objective is to deposit MSCs locally in fistulizing tracts to down-regulate the local immune response and induce wound healing. Results from upcoming and ongoing clinical trials will set the path of these novel therapeutic options that have the capability to successfully treat severe refractory Crohn's patients. PMID- 27366223 TI - Current approaches for optimizing the benefit of biologic therapy in ulcerative colitis. AB - As biologic-based medication options for ulcerative colitis expand, our understanding of their optimal use in clinical practice is advancing as well. The appropriate use of combination therapy with immunomodulators can reduce the immunogenicity of biologic agents and raise serum drug levels of the biologic. A treat-to-target strategy with objective assessments of disease activity clearly defines the goals of biologic drug treatment. Mucosal healing is an evolving treatment goal and is associated with long-term remission and reduced incidence of colectomy. Furthermore, regular reassessments and therapeutic drug monitoring can allow clinicians to make evidence-based changes in therapy. Biologic drug de escalation or re-initiation are less well developed topics, but are emerging areas of study. We review the evidence underlying these advances and a modern approach to the use of biologic therapy in ulcerative colitis. PMID- 27366224 TI - Epigenetic therapy in gastrointestinal cancer: the right combination. AB - Epigenetics is a relatively recent field of molecular biology that has arisen over the past 25 years. Cancer is now understood to be a disease of widespread epigenetic dysregulation that interacts extensively with underlying genetic mutations. The development of drugs targeting these processes has rapidly progressed; with several drugs already FDA approved as first-line therapy in hematological malignancies. Gastrointestinal (GI) cancers possess high degrees of epigenetic dysregulation, exemplified by subtypes such as CpG island methylator phenotype (CIMP), and the potential benefit of epigenetic therapy in these cancers is evident. The application of epigenetic drugs in solid tumors, including GI cancers, is just emerging, with increased understanding of the cancer epigenome. In this review, we provide a brief overview of cancer epigenetics and the epigenetic targets of therapy including deoxyribonucleic acid (DNA) methylation, histone modifications, and chromatin remodeling. We discuss the epigenetic drugs currently in use, with a focus on DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors, and explain the pharmacokinetic and mechanistic challenges in their application. We present the strategies employed in incorporating these drugs into the treatment of GI cancers, and explain the concept of the cancer stem cell in epigenetic reprogramming and reversal of chemo resistance. We discuss the most promising combination strategies in GI cancers including: (1) epigenetic sensitization to radiotherapy, (2) epigenetic sensitization to cytotoxic chemotherapy, and (3) epigenetic immune modulation and priming for immune therapy. Finally, we present preclinical and clinical trial data employing these strategies thus far in various GI cancers including colorectal, esophageal, gastric, and pancreatic cancer. PMID- 27366225 TI - Novel perspectives on therapeutic modulation of the gut microbiota. AB - The gut microbiota contributes to the maintenance of health and, when disrupted, may drive gastrointestinal and extragastrointestinal disease. This can occur through direct pathways such as interaction with the epithelial barrier and mucosal immune system or indirectly via production of metabolites. There is no current curative therapy for chronic inflammatory conditions such as inflammatory bowel disease, which are complex multifactorial disorders involving genetic predisposition, and environmental triggers. Therapies are directed to suppress inflammation rather than the driver, and these approaches are not devoid of adverse effects. Therefore, there is great interest in modulation of the gut microbiota to provide protection from disease. Interventions that modulate the microbiota include diet, probiotics and more recently the emergence of experimental therapies such as fecal microbiota transplant or phage therapy. Emerging data indicate that certain bacteria can induce protective immune responses and enhance intestinal barrier function, which could be potential therapeutic targets. However, mechanistic links and specific therapeutic recommendations are still lacking. Here we provide a pathophysiological overview of potential therapeutic applications of the gut microbiota. PMID- 27366226 TI - The interplay between the microbiome and the adaptive immune response in cancer development. AB - The data from different studies suggest a bacterial role in cancer genesis/progression, often modulating the local immune response. This is particularly so at the mucosal level where the bacterial presence is strong and the immune system is highly reactive. The epithelial surfaces of the body, such as the skin and mucosa, are colonized by a vast number of microorganisms, which represent the so-called normal microbiome. Normally the microbiome does not cause a proinflammatory response because the immune system has developed different strategies for the tolerance of commensal bacteria, but when these mechanisms are impaired or new pathogenic bacteria are introduced into this balanced system, the immune system reacts to the microbiome and can trigger tumor growth in the intestine. In this review, we discuss the potential role of the bacterial microbiome in carcinogenesis, focusing on the direct and indirect immune adaptive mechanisms, that the bacteria can modulate in different ways. PMID- 27366228 TI - Understanding the gastrointestinal manifestations of Fabry disease: promoting prompt diagnosis. AB - Fabry disease is a rare X-linked lysosomal storage disease characterized by the dysfunction of multiple systems, including significant gastrointestinal involvement such as diarrhea, abdominal pain, early satiety and nausea. The gastrointestinal symptoms of Fabry disease are thought to be due to neuropathic and myopathic changes leading to symptoms of dysmotility that are encountered in many other disorders. The gastrointestinal symptoms can often be one of the presenting signs of the disease in childhood, but can be misdiagnosed by gastroenterologists for many years due to their nonspecific presentation. As the chief treatment for Fabry is enzyme-replacement therapy that has been shown to stabilize and possibly reverse disease course, recognition of these symptoms and early diagnosis in an attempt to prevent progression with treatment, is critical. PMID- 27366229 TI - Endoscopic ultrasound-assisted gastrointestinal hemostasis: an evolving technique. AB - Gastrointestinal bleeding can range from grossly visible blood in stool or vomitus to microscopic bleed. However, any kind of bleeding can lead to potential life-threatening consequences. A small proportion of patients with gastrointestinal bleeding remain refractory to initial endoscopic hemostasis. While some are successfully managed by repeat endoscopic intervention, a few fail to respond or are not amenable to endoscopic hemostasis. As of now, the next level of intervention is passed on to either surgeons or interventional radiologists. There is new evidence suggesting the increased utility of endoscopic ultrasound (EUS) in diagnosis and treatment of culprit vascular lesions across the gut. In addition, EUS-assisted technique has also been used in the primary prevention of bleeding from gastroesophageal varices. In this review article, we have summarized case series and reports describing the use of EUS assisted hemostasis. Indications, techniques, complications and success rates reported are discussed. While most of the authors describe their experience with primary and secondary treatment of gastric varices, treatment of other gastrointestinal lesions with EUS assisted hemostatic techniques is also discussed. PMID- 27366230 TI - Incidence, characterization, and clinical impact analysis of peginterferon beta1a immunogenicity in patients with multiple sclerosis in the ADVANCE trial. AB - BACKGROUND: Efficacy of interferon beta in multiple sclerosis (MS) can be dampened in patients who develop neutralizing antidrug antibodies (NAbs). Peginterferon beta1a is an interferon conjugated with a polyethylene glycol (PEG) moiety. Pegylation increases a drug's half life and exposure, and may also reduce immunogenicity. OBJECTIVE: The objective of this study was to characterize the incidence and impact of immunogenicity to peginterferon beta1a over 2 years in patients with MS. METHODS: Patients with relapsing-remitting MS (N = 1512) were randomized to subcutaneous peginterferon beta1a 125 MUg every 2 or 4 weeks, or placebo, for 1 year; patients in the placebo group were rerandomized to active treatment in year 2. The incidence and titers of binding antibodies (BAbs) and NAbs to interferon and antibodies to PEG (anti-PEG) were assessed in analytically validated assays. The clinical impact of immunogenicity on relapse and magnetic resonance imaging endpoints was evaluated. RESULTS: Over 2 years, 6%, less than 1%, and 7% of patients developed anti-interferon BAbs, NAbs, and anti-PEG antibodies, respectively. There was no discernible clinically meaningful effect of antibody status on the pharmacodynamic, efficacy, or safety parameters evaluated, although these analyses were limited by the low incidence of treatment emergent antibodies. CONCLUSION: The treatment effect of peginterferon beta1a in patients with relapsing-remitting MS is not expected to be attenuated by immunogenicity. PMID- 27366227 TI - The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: a tripartite pathophysiological circuit with implications for new therapeutic directions. AB - We discuss the tripartite pathophysiological circuit of inflammatory bowel disease (IBD), involving the intestinal microbiota, barrier function, and immune system. Dysfunction in each of these physiological components (dysbiosis, leaky gut, and inflammation) contributes in a mutually interdependent manner to IBD onset and exacerbation. Genetic and environmental risk factors lead to disruption of gut homeostasis: genetic risks predominantly affect the immune system, environmental risks predominantly affect the microbiota, and both affect barrier function. Multiple genetic and environmental 'hits' are likely necessary to establish and exacerbate disease. Most conventional IBD therapies currently target only one component of the pathophysiological circuit, inflammation; however, many patients with IBD do not respond to immune-modulating therapies. Hope lies in new classes of therapies that target the microbiota and barrier function. PMID- 27366231 TI - Therapy satisfaction and adherence in patients with relapsing-remitting multiple sclerosis: the THEPA-MS survey. AB - BACKGROUND: Improved clinical effectiveness and therefore positive modification of multiple sclerosis (MS) with basic therapy can be achieved by long-term regular intake of drugs as prescribed but investigations have shown that a high percentage of patients do not take their medications as prescribed. OBJECTIVES: We assessed the satisfaction and adherence of patients with MS with their current disease-modifying treatment under clinical practice conditions. We compared different facets of satisfaction as well as their internal relationship and identified predictors in an exploratory manner. METHODS: Therapy satisfaction in patients with relapsing-remitting multiple sclerosis (THEPA-MS) was a noninterventional, prospective cross-sectional study performed throughout Germany in 2013 and 2014, and included patients with clinically isolated syndrome or relapsing-remitting MS. We applied a standardized approach to document satisfaction and adherence by patient-reported outcomes (Treatment Satisfaction Questionnaire for Medication) as well as by physician ratings. RESULTS: Of 3312 patients with a mean age of 43.7 years, 73.3% were women and the mean level of disability according to the Expanded Disability Status Scale was 2.29; 13.3% did not receive any medication at the time of documentation, 21.3% received interferon beta1a intramuscularly, 20.7% had interferon beta1a subcutaneously, 17.0% had interferon beta1b subcutaneously and 23.7% had glatiramer acetate. Adherence rates varied between 60% (lifetime) and 96.5% (current medication). Differences between current medications were found for side effects and convenience scores but not for effectiveness, satisfaction and adherence. Higher global satisfaction and effectiveness were associated with fewer relapses, longer duration of medication, lower disability score and the absence of several side effects. CONCLUSION: In a connected model of patient satisfaction, effectiveness, side effects, convenience and adherence, patients' individual needs and concerns have to be addressed. Most differences were found with respect to side effects and convenience of treatment. Therefore, an improvement in these two domains seems to be the most promising proximate approach to elevate adherence levels. PMID- 27366232 TI - One-time intrathecal triamcinolone acetonide application alters the redox potential in cerebrospinal fluid of progressive multiple sclerosis patients: a pilot study. AB - INTRODUCTION: Cerebrospinal fluid analysis may provide insight into the interplay between chronic inflammation and response to treatment. OBJECTIVES: To demonstrate the impact of one intrathecal triamcinolone injection on the redox potential and on ascorbyl radical appearance in the cerebrospinal fluid of chronic progressive multiple sclerosis patients. METHODS: A total of 16 patients received 40 mg triamcinolone. Electron-spin resonance spectroscopy measured the oxidation range after copper ion [Cu (II)] addition and ascorbyl-radical bioavailability. RESULTS: There was an increase of Cu (II) ion absorption, which reflects an augmented content of reduced proteins. Ascorbyl radicals were present in contrast to healthy controls according to the literature. CONCLUSION: Intrathecal steroid application alters the redox potential in cerebrospinal fluid. Our findings support the beneficial role of steroids on oxidative stress generally demonstrated by ascorbyl radical appearance. Reactive oxygen species decline is necessary for an upregulated production of reduced proteins. PMID- 27366233 TI - Cognitive functions over the course of 1 year in multiple sclerosis patients treated with disease modifying therapies. AB - OBJECTIVES: Disease-modifying therapies (DMTs) are applied to delay or prevent disease progression in multiple sclerosis (MS). While this has mostly been proven for physical symptoms, available studies regarding long-term effects of DMTs on cognitive functions are rare and sometimes inconsistent due to methodological shortcomings. Particularly in the case of fingolimod, comprehensive data on cognitive functions are not yet available. Therefore, we set out to reliably assess cognitive functions in patients with relapsing-remitting MS (RRMS) treated with DMTs over 1 year. METHODS: Cognitive functions were assessed with eight tests at three timepoints: baseline, 6-month follow up and 12-month follow up. First, we investigated whether the stability of cognitive functions (i.e. not falling below the 5% cut-off in more than one test) over 1 year in RRMS patients (n = 41) corresponds to the stability in healthy individuals (n = 40) of a previous study. Second, we compared the percentage of declined and improved patients in the different tests. Third, we compared patients treated with fingolimod (n = 22) with patients treated with natalizumab (n = 11) with regard to cognitive stability. Fourth, based on the patient data, the Reliable Change Index was applied to compute cut-offs for reliable cognitive change. RESULTS: Approximately 75% of RRMS patients treated with DMTs remained stable over the course of 1 year. The Paced Auditory Serial Addition Test (PASAT) and the Spatial Recall Test (SPART), produced improvements in 12.5% and 30.6%, respectively, probably due to practice effects. Patients treated with fingolimod did not differ from patients treated with natalizumab with regard to cognitive stability. CONCLUSIONS: Cognitive functions remain relatively stable under DMT treatment over 1 year, irrespective of the type of medication. Furthermore, the tests PASAT and SPART should be interpreted cautiously in studies examining performance changes over time. The provided RCI norms may help clinicians to determine whether a difference in two measurements observed in a RRMS patient is reliable. PMID- 27366234 TI - Immunoadsorption in patients with neuromyelitis optica spectrum disorder. AB - INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a neuroinflammatory disorder of the central nervous system, distinct from multiple sclerosis by affecting predominantly the optic nerve and the spinal cord, and mediated by antibodies directed against aquaporin 4 (AQP4-ab) as a possible pathomechanistic hallmark of NMOSD. Therapeutic options include immunosuppression with steroids or B-cell-depleting agents as baseline therapies, as well as plasma exchange (PLEX) and/or immunoadsorption (IA) during relapses. Until now, data concerning the efficacy of IA alone are scarce. METHODS: Visual evoked potentials (VEPs), visual acuity and changes of symptoms at relapse leading to admission in NMOSD patients (n = 10) treated with IA in a single-centre setting were evaluated retrospectively. RESULTS: All patients profited from the procedure and showed an amelioration of admission symptoms. Three patients improved in visual acuity, another three patients remained stable, whereas five patients showed an improvement in VEPs. DISCUSSION: In this small cohort, IA constitutes a valid therapeutic option for patients with NMOSD as an equivalent to PLEX. Analysis in larger cohorts is warranted. PMID- 27366235 TI - Quantitative analysis of multiple sclerosis patients' preferences for drug treatment: a best-worst scaling study. AB - BACKGROUND: With recent developments in drug therapy for multiple sclerosis (MS), new treatment options have become available presenting patients with complex treatment decisions. OBJECTIVES: The objective of this study was to elicit patients' preferences for different attributes of MS drug therapy. METHODS: A representative sample of patients with MS across Canada (n=189) participated in a best-worst scaling study to quantify preferences for different attributes of MS drug therapy, including delaying progression, improving symptoms, preventing relapse, minor side effects, rare but serious adverse events (SAEs), and route of administration. Conditional logit models were fitted to estimate the relative importance of each attribute in influencing patients' preferences. RESULTS: A latent-class analysis revealed heterogeneity of preferences across respondents, with preferences differing across five classes. The most important attributes of drug therapy were the avoidance of SAEs for three classes and the improvement of symptoms for two other classes. Only a smaller group of patients demonstrated a specific preference for avoiding SAEs, and route of administration. CONCLUSION: This study shows that preferences for drug therapy among patients with MS are different, some of which can be explained by experiences with their disease and treatment. These findings can help to inform the focus of interactions that healthcare practitioners have with patients with MS, as well as further drug development. PMID- 27366236 TI - Immunoadsorption versus plasma exchange versus combination for treatment of myasthenic deterioration. AB - OBJECTIVES: The goal of this study was to analyze safety and assess the efficacy of standard plasma exchange (PE) compared with immunoadsorption (IA) alone, or an alternating combination of both in deteriorating myasthenia gravis (MG). METHODS: A total of 72 patients with MG who had received PE procedures for treatment of severe deterioration were retrospectively analyzed. They received either five cycles of PE (1-1.5 plasma volumes), or five cycles of IA in line with plasma separation, or a sequential alternating procedure of one cycle of PE followed by two cycles of IA, which was repeated once or more if needed. RESULTS: A total of 19 patients received PE, 24 patients IA, and 29 the alternating combination therapy. All groups were equally distributed by sex and mean MG score before treatment. The number of treatment cycles and days on therapy did not differ between the groups. Mean MG scores at discharge were 3.0 (PE), 1.8 (IA) and 1.6 (combination) (p = 0.028 for combination versus PE). Inpatient time was 30.7 days (PE), 22.3 days (IA) and 20.0 days in combination therapy (p < 0.05 for combination versus PE). Side effects such as allergic reactions or hypocoagulability were significantly more frequent in the PE group (37% in PE versus 4% in IA and 3.6% in the alternating combination, p < 0.05). CONCLUSION: Semiselective IA in combination with PE, and to a lesser extent IA alone, was associated with a shorter hospital stay and more pronounced reduction of the MG score than PE. PMID- 27366237 TI - Direct stroke unit admission of intravenous tissue plasminogen activator: safety, clinical outcome, and hospital cost savings. AB - BACKGROUND: In the USA, stable intravenous tissue plasminogen activator (IV tPA) patients have traditionally been cared for in an intensive care unit (ICU). We examined the safety of using an acuity-adaptable stroke unit (SU) to manage IV tPA patients. METHODS: We conducted an observational study of consecutive patients admitted to our acuity-adaptable SU over the first 3 years of operation. Safety was assessed by symptomatic intracerebral hemorrhage (sICH) rates, systemic hemorrhage (SH) rates, tPA-related deaths, and transfers from SU to ICU; cost savings and length of stay (LOS) were determined. RESULTS: We admitted 333 IV tPA patients, of which 302 were admitted directly to the SU. A total of 31 (10%) patients had concurrent systemic hemodynamic or pulmonary compromise warranting direct ICU admission. There were no differences in admission National Institutes of Health Stroke Scale scores between SU and ICU patients (9.0 versus 9.5, respectively). Overall sICH rate was 3.3% (n = 10) and SH rate was 2.9 (n = 9), with no difference between SU and ICU patients. No tPA-related deaths occurred, and no SU patients required transfer to the ICU. Estimated hospital cost savings were US$362,400 for 'avoided' ICU days, and hospital LOS decreased significantly (p = 0.001) from 9.8 +/- 15.6 days (median 5) in year 1, to 5.2 +/- 4.8 days (median 3) by year 3. CONCLUSIONS: IV tPA patients may be safely cared for in a SU when nurses undergo extensive education to ensure clinical competence. Use of the ICU solely for monitoring may constitute significant overuse of system resources at an expense that is not associated with additional safety benefit. PMID- 27366238 TI - Clinical efficacy of combined sodium dimercaptopropanesulfonate and zinc treatment in neurological Wilson's disease with D-penicillamine treatment failure. AB - OBJECTIVES: There are limited pharmacological treatments for patients with neurological Wilson's disease (WD) and a history of copper-chelating treatment failure. METHODS: We retrospectively evaluated the clinical records of 38 patients with WD who were treated with sodium dimercaptopropanesulfonate (DMPS) and zinc (group 1) or zinc alone (group 2). All patients had a history of neurological deterioration during their previous treatment with D-penicillamine (DPA). RESULTS: Twenty-one patients were treated with intravenous DMPS for 4 weeks, followed by zinc gluconate for 6 months, and the treatment protocol was repeated twice. Relative to the baseline, repeated DMPS therapy and zinc maintenance therapy decreased neurological scores continuously (p < 0.01). Sixteen patients (76.2%) demonstrated neurological improvements after 1 year of therapy and four patients (19.0%) exhibited neurological deterioration at the follow-up session. In addition, 17 patients were treated with zinc monotherapy for 12 months. Two patients (11.8%) demonstrated neurological improvements and five patients (29.4%) exhibited neurological deterioration. Compared with the patients in group 2, a greater improvement ratio (p < 0.01) and lower deterioration ratio (p < 0.01) were observed in the patients in group 1 after 1 year of therapy. CONCLUSIONS: Our findings indicate that the safety and efficacy of combined treatment of DMPS and zinc is superior to those of zinc monotherapy in patients with neurological WD with a history of DPA treatment failure. PMID- 27366239 TI - The diagnosis and management of idiopathic intracranial hypertension and the associated headache. AB - Idiopathic intracranial hypertension (IIH) is a challenging disorder with a rapid increasing incidence due to a close relation to obesity. The onset of symptoms is often insidious and patients may see many different specialists before the IIH diagnosis is settled. A summary of diagnosis, symptoms, headache characteristics and course, as well as existing evidence of treatment strategies is presented and strategies for investigations and management are proposed. PMID- 27366240 TI - Web-based interventions in multiple sclerosis: the potential of tele rehabilitation. AB - The World Wide Web is increasingly used in therapeutic settings. In this regard, internet-based interventions have proven effective in ameliorating several health behaviors, amongst them physical activity behavior. Internet-delivered interventions have shown positive effects on physical activity and physical function in persons with MS (pwMS). In this review we give an overview on several online exercise programs for pwMS and discuss the advantages and drawbacks of web based interventions. Although participants of online exercise programs reported a high acceptance and satisfaction with the intervention, decreasing compliance was a major issue. A possible remedy might be the implementation of game-design elements to increase compliance and long-term adherence to internet-delivered interventions. In addition we believe that the integration of social networks seems to be a promising strategy. PMID- 27366241 TI - Subcutaneous immunoglobulins in the treatment of chronic immune-mediated neuropathies. AB - Intravenous immunoglobulins represent an established therapy for the treatment of chronic immune-mediated neuropathies, specifically chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) as well as multifocal motor neuropathies (MMNs). For the treatment of antibody deficiency syndromes, subcutaneous immunoglobulins (SCIgs) have represented a mainstay for decades. An emerging body of evidence suggests that SCIg might also exhibit clinical efficacy in CIDP and MMN. This article reviews the current evidence for clinical effectiveness, as well as safety of SCIg for the treatment of immune-mediated neuropathies, and addresses remaining open questions in this context. We conclude that despite the need for controlled long-term studies to demonstrate long-term efficacy of SCIg in immune-mediated neuropathies, SCIg may already represent a potential therapeutic alternative for selected patients. PMID- 27366242 TI - Dimethyl fumarate may still have a role in progressive multiple sclerosis. PMID- 27366243 TI - Endoscopic management of cerebrospinal fluid rhinorrhea. AB - Cerebrospinal fluid (CSF) rhinorrhea occurs due to communication between the intracranial subarachnoid space and the sinonasal mucosa. It could be due to trauma, raised intracranial pressure (ICP), tumors, erosive diseases, and congenital skull defects. Some leaks could be spontaneous without any specific etiology. The potential leak sites include the cribriform plate, ethmoid, sphenoid, and frontal sinus. Glucose estimation, although non-specific, is the most popular and readily available method of diagnosis. Glucose concentration of > 30 mg/dl without any blood contamination strongly suggests presence and the absence of glucose rules out CSF in the fluid. Beta-2 transferrin test confirms the diagnosis. High-resolution computed tomography and magnetic resonance cisternography are complementary to each other and are the investigation of choice. Surgical intervention is indicated, when conservative management fails to prevent risk of meningitis. Endoscopic closure has revolutionized the management of CSF rhinorrhea due to its less morbidity and better closure rate. It is usually best suited for small defects in cribriform plate, sphenoid, and ethmoid sinus. Large defects can be repaired when sufficient experience is acquired. Most frontal sinus leaks, although difficult, can be successfully closed by modified Lothrop procedure. Factors associated with increased recurrences are middle age, obese female, raised ICP, diabetes mellitus, lateral sphenoid leaks, superior and lateral extension in frontal sinus, multiple leaks, and extensive skull base defects. Appropriate treatment for raised ICP, in addition to proper repair, should be done to prevent recurrence. Long follow-up is required before leveling successful repair as recurrences may occur very late. PMID- 27366244 TI - Brainstem epidermoid cyst: An update. AB - The incidence of epidermoid tumors is between 1% and 2% of all intracranial tumors. The usual locations of epidermoid tumor are the parasellar region and cerebellopontine angle, and it is less commonly located in sylvian fissure, suprasellar region, cerebral and cerebellar hemispheres, and lateral and fourth ventricles. Epidermoid cysts located in the posterior fossa usually arise in the lateral subarachnoid cisterns, and those located in the brain stem are rare. These epidermoids contain cheesy and flaky white soft putty like contents. Epidermoid cysts are very slow growing tumors having a similar growth pattern of the epidermal cells of the skin and develop from remnants of epidermal elements during closure of the neural groove and disjunction of the surface ectoderm with neural ectoderm between the third and fifth weeks of embryonic life. We are presenting an interesting case of intrinsic brainstem epidermoid cyst containing milky white liquefied material with flakes in a 5-year-old girl. Diffusion weighted imaging is definitive for the diagnosis. Ideal treatment of choice is removal of cystic components with complete resection of capsule. Although radical resection will prevent recurrence, in view of very thin firmly adherent capsule to brainstem, it is not always possible to do complete resection of capsule without any neurological deficits. PMID- 27366245 TI - A novel equine-derived pericardium membrane for dural repair: A preliminary, short-term investigation. AB - BACKGROUND: A large variety of biological and artificial materials are employed in dural repair, each of them with major limitations. Autologous grafts have limited availability and require an additional incision and surgical time. Cadaveric preparations and heterologous materials entail the risk of iatrogenic transmission of prions, whereas synthetic substitutes have been reported to cause inflammatory reactions and graft rejection. An equine-derived pericardium membrane has been developed (Heart((r)), Bioteck, Vicenza, Italy) with mechanical and safety-related features that could make it suitable for neurosurgical application. AIMS: This preliminary study aimed to evaluate the short-term safety and efficacy of the Heart((r)) membrane in dural repair procedures following meningioma surgeries. SUBJECTS AND METHODS: Medical records of patients who were surgically treated for an intracranial meningioma and underwent duraplasty with the Heart((r)) membrane were reviewed retrospectively. The occurrence of any graft-related complications such as cerebrospinal fluid (CSF) leakage, postoperative hematoma, wound infection, meningitis, and neurological symptoms was analyzed. RESULTS: Eight patients were identified as meeting the inclusion criteria. A watertight closure was achieved in all of them. Postoperatively, no patients exhibited CSF leak, cerebral contusion, hemorrhage, or wound infection. The 1-month radiological follow-up revealed no evidence of pseudomeningocele, wound breakdown, or meningitis. Neurologic complications were observed in three patients but not directly imputable to the dural substitute or its application. CONCLUSIONS: In all the patients, the pericardium membrane enabled achievement of a watertight dural closure without graft-related adverse events. Further investigations should be performed to assess medium- and long-term clinical outcomes in a larger set of patients. PMID- 27366246 TI - Our technique of midsagittal splitting laminoplasty for compressive cervical myelopathy and its short-term results. AB - OBJECTIVE: The aim of this study was to discuss the technique of midsagittal splitting laminoplasty and to compare its short-term follow-up results with laminectomy in cases of compressive cervical spinal cord myelopathy. MATERIALS AND METHODS: Exclusion criteria were as follows: Intramedullary compressive lesions, kyphotic cervical spine, previous spinal surgeries, and defective anterior vertebral column. Twenty patients (10 each of laminoplasty and laminectomy groups) were prospectively studied from 2005 to 2008. After clinico radiological assessment, laminoplasty or laminectomy was performed in patients aged <50 years and >50 years, respectively. The laminoplasty was performed by splitting the excised lamina in midline up to the tip of spinous process. Follow up was done by neurosurgical cervical spine scoring, Nurick's grading, and the final outcome was determined by Odom's criteria. RESULTS: The mean operative time and blood loss in laminoplasty and laminectomy was 100 +/- 0.87 (range 90-140 min), 80 +/- 0.67 (range 75-100 min) P = 0.04; and 65 +/- 0.07 (range 60-90 ml) and 68 +/- 0.61 (range 65-80 ml) P = 0.09, respectively. There were no intraoperative accidents, and no postoperative neurological deterioration/recurrence of symptoms. One patient who underwent laminectomy alone developed progressive kyphosis of the spine, whereas one having rheumatoid arthritis and long symptom duration didn't improve. 85% (17/20 patients) had sustained excellent to fair outcome (improvement by at least one Nurick's grade). CONCLUSIONS: The technique used by us was simple, effective, and inexpensive. There was no minimal postoperative morbidity, although long-term results are awaited. PMID- 27366247 TI - The role of subgaleal suction drain placement in chronic subdural hematoma evacuation. AB - INTRODUCTION: There is lack of uniformity about the preferred surgical treatment, role of drain, and type of drain among various surgeons in chronic subdural hematoma (CSDH). The present study is aimed to evaluate role of subgaleal drain. MATERIALS AND METHODS: This was a prospective study of 260 patients of CSDH treated surgically. Burr-hole irrigation with and without suction drain was done in 140 and 120 patients, respectively. Out of 120 patients without suction drain 60 each were managed by single and two burr holes. Pre- and postoperative GCS was recorded. Recurrent hematomas, CSDH secondary to tumor, due to intracranial hypotension, coagulopathy, children below 18 years, and patients treated by twist drill craniostomy or craniotomy were excluded. Subgaleal closed-system drainage with low negative pressure was used. RESULTS: Age of the patients ranged from 18 to 75 years with mean age of 57 years. There were 9, 47, 204 patients in GCS of 3 8, 9-12, and 13-15, respectively. Both the groups were comparable in terms of age, etiology, gender, and neurological status. There was no difference in the mortality in both the group. The recurrence and postoperative pneumocephalus was significantly less in suction drain group as compared to without drain group. There was no infection or any other complication related to suction drainage. CONCLUSION: Subgaleal closed suction drainage was safe, simple, and effective in the management of CSDH. Recurrence rate was low in the suction drain group. PMID- 27366248 TI - Surgical outcome in cystic vestibular schwannomas. AB - BACKGROUND: Cystic vestibular schwannomas (VS) form a rare subgroup that differs from the solid variant clinically, radiologically, and histopathologically. These tumors also vary in their surgical outcome and carry a different risk of post operative complications. We analyzed our series of 64 patients with cystic VS and discuss the technical difficulties related to total excision of these tumors and focus on complication avoidance. MATERIALS AND METHODS: A retrospective review of cystic VS surgically managed over a span of 11 years. The case records were evaluated to record the clinical symptoms and signs, imaging findings, surgical procedure, complications, and follow-up data. Post-operative facial nerve palsy was analyzed with respect to tumor size and tumor type. RESULTS: Progressive hearing impairment was the most common initial symptom (76.6%). Atypical initial symptoms were present in 15 patients (23.4%). Preoperatively, 78% patients had good facial nerve function (HB grade 1, 2) and 22% had intermediate (HB grade 3, 4) to poor (HB grade 5 and 6) function. Mean tumor size was 4.1 cm. Complete tumor removal was achieved in 53 patients (83%). The facial nerve was anatomically intact but thinned out after tumor excision in 38 patients (59.4%). Ninety percent patients had either intermediate or poor facial nerve function at follow-up. Poor facial nerve outcome was associated with giant tumors and peripherally located, thin-walled cystic tumors. CONCLUSION: Resection of cystic VS is complicated by peritumoral adhesions of the capsule to the nerve. Extensive manipulation of the nerve in order to dissect the tumor-nerve barrier results in worse facial nerve outcome. The outcome is worse in peripherally located, thin walled cystic VS as compared to centrally located, thick-walled cystic tumors. Subtotal excision may be justified, especially in tumors with dense adhesion of the cyst wall to the facial nerve in order to preserve nerve integrity. PMID- 27366249 TI - Tuberculosis of spine: An experience of 30 cases over two years. AB - OBJECTIVE: Tuberculosis of spine is still a very common condition in India. Here, the results of 30 cases of tuberculosis of spine treated in SSG Hospital, Vadodara, Gujarat, in the last two years, are reviewed. MATERIALS AND METHODS: A total of 30 patients with tuberculosis of spine were treated in SSG Hospital in the last two years. They were classified into three groups, based on the GATA, GATA = Gulhane Askeri Tip Akademisi (Gulhane Military Medical Academy) classification for spinal tuberculosis, with few modifications. Their neurologic status was evaluated by the Frankel's grading. All the patients were started on four drug anti-tuberculosis medication given every alternate day as per the DOTS and RNTCP program of the Government of India for 6 months. Patients in group 1 were treated by bed rest, analgesics, and antituberculous drugs after confirmation of the diagnosis by CT-guided biopsy. Patients in group 2 were treated by surgical of USG-guided aspiration of abscesses followed by full course of antituberculous drugs. Twenty-one patients in group 3 underwent surgery. A single-stage anterior decompression and anterior fixation was done in all the cases. RESULTS: All the nine patients in group I and 2 responded well to medical management and were cured of the disease. Out of the 21 operated patients, 19 had significant improvement in neurological status and return to their normal activities. The first operated patient died. The neurological status of one patient did not improve till 1 month after surgery and was lost to follow-up. Thus, 100% of group 1 and 2 patients were cured of the disease and 90% of group 3 patients had good neurological recovery. CONCLUSIONS: If treated timely and adequately, the outcome for tuberculosis of spine is relatively good. Anterolateral approach to the spine with decompression and fixation gives good result with respect to neurological function. PMID- 27366250 TI - Primary intracranial lymphomas. AB - BACKGROUND: Primary CNS lymphoma (PCNSL), a rare form of aggressive extranodal non-Hodgkin's lymphoma (NHL), has increased in incidence during the last three decades and occurs in both immune compromised and immune competent hosts. It has an overall poor prognosis. OBJECTIVE: This study attempts to further delineate the clinico-pathological, immunohistochemical and radiological profile of PCNSL at Jeddah to King Faisal Hospital and Research Center. METHODS: Computerized search through the archives of King Faisal Hospital and Research Centre between July 2000- December 2012 identified 15 patients with pathologically confirmed PCNSL. These were analyzed retrospectively. Their clinico-pathological, immunohistochemical and radiological data were analyzed. RESULTS: Of the 15 PCNSL patients, 8 (53.3%) were females and 7 (46.6%) were males. There was female predilection especially in the age group of 40-59 years. Mean age at diagnosis for all patients was 50.4 years. There was no patient in the pediatric age group. The most common location in the brain was the frontal region in 7 patients (46.6%), 7 (46.6%) had multiple intracranial masses; all 15 (100%) were Non Hodgkin B-cell lymphomas, among which 13 (86.6%) were diffuse large B-cell lymphomas. All 15 (100%) cases showed diffuse and strong positivity for CD 45, and CD 20. Fourteen patients were immune competent while one was immune compromised. CONCLUSIONS: PCNSL often occurs in middle-aged and aged patients. There is female predilection especially in the middle age. Frontal region is the most common location with diffuse large B-cell lymphoma being the predominant subtype. PMID- 27366251 TI - The "focus on aneurysm" principle: Classification and surgical principles of management of concurrent arterial aneurysm with arteriovenous malformation causing intracranial hemorrhage. AB - CONTEXT: Concurrent arterial aneurysms (AAs) occurring in 2.7-16.7% patients harboring an arteriovenous malformation (AVM) aggravate the risk of intracranial hemorrhage. AIM: We evaluate the variations of aneurysms simultaneously coexisting with AVMs. A classification-based management strategy and an abbreviated nomenclature that describes their radiological features is also proposed. SETTING: Tertiary care academic institute. STATISTICS: Test of significance applied to determine the factors causing rebleeding in the groups of patients with concurrent AVM and aneurysm and those with only AVMs. SUBJECTS AND METHODS: Sixteen patients (5 with subarachnoid hemorrhage and 11 with intracerebral/intraventricular hemorrhage; 10 with low flow [LF] and 6 with high flow [HF] AVMs) underwent radiological assessment of Spetzler Martin (SM) grading and flow status of AA + AVM. Their modified Rankin's score (mRS) at admission was compared with their follow-up (F/U) score. RESULTS: Pre-operative mRS was 0 in 5, 2 in 6, 3 in 1, 4 in 3 and 5 in 1; and, SM grade I in 5, II in 3, III in 3, IV in 4 and V in 1 patients, respectively. AA associated AVMs were classified as: (I) Flow-related proximal (n = 2); (II) flow-related distal (n = 3); (III) intranidal (n = 5); (IV) extra-intranidal (n = 2); (V) remote major ipsilateral (n = 1); (VI) remote major contralateral (n = 1); (VII) deep perforator related (n = 1); (VIII) superficial (n = 1); and (IX) distal (n = 0). Their treatment strategy included: Flow related AA, SM I-III LF AVM: aneurysm clipping with AVM excision; nidal-extranidal AA, SM I-III LF AVM: Excision or embolization of both AA + AVM; nidal-extranidal and perforator-related AA, SM IV-V HF AVM: Only endovascular embolization or radiosurgery. Surgical decision-making for remote AA took into account their ipsilateral/contralateral filling status and vessel dominance; and, for AA associated with SM III HF AVM, it varied in each patient based on diffuseness of AVM nidus, flow across arteriovenous fistula and eloquence of cortex. Follow up (F/U) (23.29 months; range: 1.5-69 months) mRS scores were 0 in 12, 2 in 2, 3 in 1 and 6 in 1 patients, respectively. CONCLUSIONS: Patients with intracranial AVMs should be screened for concurrent AAs. Further grading, management protocols and prognostication should particularly "focus on the aneurysm." PMID- 27366252 TI - Morphometric analysis of posterior fossa in Indian CP angle acoustic schwannoma patients. AB - AIM: To study the morphometry of posterior fossa in Indian CP angle schwannoma patients in order to know its influence on the extent of excision of the CP angle acoustic schwannomas. MATERIALS AND METHODS: One hundred cases of cerebellopontine angle schwannomas treated surgically by the senior author and 20 controls between January 2006 and June 2011 were consecutively investigated with computed tomography (CT) using the high-resolution CT bone windows before surgery. Evaluation of anatomic parameters of the petrous bone and posterior fossa cavity were done in all patients and controls. Data were entered in Excel software and were analyzed using NCSS software. All possible regression analysis was done to select the important variables to be included in the model to predict the excision of tumor with these variables. A prediction model was developed defining the binary outcome as total excision or subtotal excision as dependent variable and the morphometric data and grading of tumor as independent variables. RESULTS: Interpetrous distance (IP) is the distance between the two petrous apices. Sigmoid distance (IS) distance is the distance between the two sigmoid points. Sigmoid point is the point at which the scalloped impression of the sigmoid sinus straightens to join the occipital bone posteriorly. SAG is the distance between the mid IP point and the mid-point on the inner wall of the occipital bone. The PM angle was 47.8+/-4.14 degrees (38-58), the PA angle was 42.68+/-4.47 degrees (34-53), the IP distance was 2.07+/-0.13 cm (1.5-2.8), the sagittal diameter of posterior fossa was 6.22+/-0.73 cm (5.1-9.8) and the intersigmoid distance was 9.45+/-0.73 cm (7.4-11). There was no significant gender difference in the posterior fossa morphometry between patients and controls. Inter-sigmoid distance and the petrous-apex angle were more in the Indians when compared to the European population mentioned in the Mathies and Samii study. CONCLUSIONS: The posterior fossa morphological parameters of the Indian and European population differ significantly. Inter-sigmoid distance and the petrous-apex angle were more in the Indians when compared to the Europeans. There is no significant gender difference in the morphometry of the Indians. There is no significant difference between the patients and the control groups. In our study the adhesions with surrounding structures along with the posterior fossa morphometry significantly affect the extent of excision. PMID- 27366253 TI - Surgical management of acromegaly: Long term functional outcome analysis and assessment of recurrent/residual disease. AB - CONTEXT: Functional growth hormone producing adenomas have long-term deleterious effects on the visual apparatus, the cardiovascular and musculoskeletal systems, and often predispose to malignancies. Since persistence of acromegaly affects outcome and quality of life, therapeutic interventions become mandatory. AIM: This study represents an analysis of long-term clinical and endocrinal outcome of 115 patients of acromegaly after surgical management. SETTING AND DESIGN: Tertiary care retrospective study. MATERIALS AND METHODS: One hundred and fifteen patients (male:female ratio: 1:1.09) with acromegalic features were studied. Apart from acromegalic features, their main clinical presentation also included headache, diminution of vision, field defects, ptosis, irregular menstruation, diabetes insipidus, diabetes mellitus and hypertension. Six of them presented with apoplexy. Their preoperative endocrinal evaluation included basal and suppressed growth hormone (GH), prolactin and thyroid levels. On the basis of axial and coronal CT scan or multiplanar MR imaging or both, the tumors were classified according to their suprasellar and parasellar extension (Hardy's grade). Transnasal trans-sphenoidal surgery (TSS) (n = 37) and sublabial, rhinoseptal TSS (n = 72) were the preferred approaches. Six patients with significant parasellar extensions underwent trans-cranial explorations. The patients were followed up at 6 and 12 weeks and then at 6 monthly intervals. Hormonal and CT/MR evaluation were also done. Attainment of random GH value less than 2.5 ug/L, and the nadir GH value after oral glucose tolerance test (OGTT) less than 1 ug/L were used as the criteria of cure. FINDINGS: The patients were preoperatively in Hardy's tumor grade 0 (29), A (21), A+E (3), B (21), B+E (5), C (9), C+E (10), D (1) D+E (11), E (5), respectively. One hundred and one patients were available for follow-up (FU; median FU duration: 84 months; range: 6 to 132 months). Surgical cure was achieved in 73 patients following the first surgery; and, in 10 additional patients following a second intervention. No patient with a preoperative grade 0, A, B, C had a recurrence after attaining the initial remission. Recurrence after an initial cure occurred in 7 patients (overall remission rate following surgery: 75.24%). The preoperative grade of the latter patients was A+E:1, B+E:1, C+E:1, D:1, D+E:2, E:1, respectively. All these patients underwent subsequent radiotherapy (RT). The twelve patients with persistent symptoms and high GH levels following surgery underwent RT; six others with improved symptoms despite high GH levels were kept under strict observation. There was no surgical mortality. CONCLUSIONS: A high remission rate without significant morbidity could be achieved following surgical intervention in acromegalic patients. Following surgery, tumors with greater than or equal to 3 cm suprasellar height and without parasellar extension had no clinical recurrence at FU. A continuous monitoring is mandatory to pick up relapsed cases as well as those who develop delayed signs of hypopituitarism. A subset of patients who show clinical improvement following surgery but still have higher GH levels may be followed up without additional therapy unless clinical signs reappear or the serum GH levels progressively increase. PMID- 27366254 TI - Trans aqueductal, third ventricle - Cervical subarachnoid stenting: An adjuvant cerebro spinal fluid diversion procedure in midline posterior fossa tumors with hydrocephalus: The technical note and case series. AB - BACKGROUND: Persistent or progressive hydrocephalus is one of the complex problems of posterior fossa tumors associated with hydrocephalus. The author evaluated the effectiveness of single-stage tumor decompression associated with a stent technique (trans aqueductal third ventricle - Cervical subarachnoid stenting) as an adjuvant cerebro spinal fluid (CSF) diversion procedure in controlling the midline posterior fossa tumors with hydrocephalus. MATERIALS AND METHODS: Prospective clinical case series of 15 patients was evaluated from July 2006 to April 2012. Fifteen clinicoradiological diagnosed cases of midline posterior fossa tumors with hydrocephalus were included in this study. All the tumors were approached through the cerebello medullary (telo velo tonsilar) fissure technique. Following the excision of the posterior fossa tumor, a sizable stent was placed across the aqueduct from the third ventricle to the cervical subarachnoid space. RESULTS: There were nine male and six female patients with an average age of 23 years. Complete tumor excision could be achieved in 12 patients and subtotal excision with clearance of aqueduct in remaining three patients. Hydrocephalus was controlled effectively in all the patients. There were no stent related complications. CONCLUSIONS: This study showed the reliability of single stage tumor excision followed by placement of aqueductal stent. The success rate of this technique is comparable to those of conventional CSF diversion procedures. This is a simple, safe, and effective procedure for the management of persistent and or progressive hydrocephalus. This technique may be very useful in situations where the patient's follow-up is compromised and the patients who are from a poor economic background. Long-term results need further evaluation to assess the overall functioning of this stent technique. PMID- 27366255 TI - Radiological study of C3-C4 level surgical cases of cervical spondylosis. AB - OBJECTIVE: The purpose of this study was to elucidate the pathological characteristics of C3-C4 cervical spondylotic myelopathy (CSM) from the radiological study. MATERIALS AND METHODS: A total of 31 patients with single level anterior cervical discectomy and fusion (ACDF) at C3-C4 and 46 patients with single level ACDF at C5-C6 were included in this study. We selected C5-C6 level as a representative of the lower cervical level. The C3-C4 and C5-C6 levels were routinely examined to investigate the areas of the vertebral canal, subarachnoid space, and spinal cord in the cervical canal. RESULTS: The clinical study of C3-C4 ACDF patients showed that as for the C3-C4 area, the area of the cervical vertebral canal, the area of the subarachnoid space, and he transverse surface area of the spinal cord were all significantly smaller in C3-C4 ACDF patients than in C5-C6 ACDF patients. Moreover, as for the C5-C6 area, only the area of the subarachnoid space was significantly smaller in C5-C6 ACDF patients than in C3-C4 ACDF patients. Spondylotic changes predominated at both the C3-C4 and C5-C6 levels. However, in the C5-C6 ACDF patients, spondylotic changes tended to predominate only at the operation level at C5-C6. CONCLUSIONS: Aging process develops from lower cervical to upper cervical level. Moreover, this static factor in conjunction with dynamic factor (instability) was the causative factors for the CSM in C3-C4 ACDF patients. PMID- 27366256 TI - Indocyanine green as an adjunct for resection of insular gliomas. AB - OBJECTIVE: Many controversies exist regarding the extent of resection for insular gliomas and the timing of resection. Several techniques and adjuncts are used to maximize safety during resection of these tumors. We describe the use of indocyanine green (ICG) to identify the branches of the middle cerebral artery and discuss its utility to increase safety for resection for insular gliomas. MATERIALS AND METHODS: Five patients with insular gliomas were surgically treated by the authors from June 2013 to June 2014. The patients presented with complaints of either a headache or recurring episodes of convulsions. All the patients were operated with the aid of neuronavigation and tractography. The long perforating branches of the middle cerebral artery course through the insula and pass onward to supply the corona radiata. It is essential to preserve these vessels to prevent postoperative neurological deficits. ICG (Aurogreen) was used to identify and preserve the long perforating arteries of the middle cerebral artery. RESULTS: ICG dye correctly identified the long perforating branches of the middle cerebral artery and easily distinguished these vessels from the short perforating branches. All the branches of the middle cerebral artery that coursed through the tumor and had an onward course were preserved in all the patients. Only one patient developed a transient right sided hemiparesis that had improved at follow-up. CONCLUSIONS: Surgery for insular gliomas is challenging due to its location adjacent to eloquent areas, important white fiber tracts and the course of the middle cerebral artery within it. ICG is useful to identify and preserve the long perforating branches of the middle cerebral artery that course through the tumor and traverse onward to supply the corona radiata. PMID- 27366257 TI - Outcome of laminoplasty in cervical spinal cord injury with stable spine. AB - BACKGROUND AND OBJECTIVE: Cervical spinal cord injury (CSCI) with a stable spine has been increasing as the elderly population is dramatically increasing all over the world. In this study, we evaluated the neurological outcome of decompression surgery (laminoplasty) for these patients. MATERIALS AND METHODS: Forty-one patients with CSCI with stable spine who underwent decompression surgery (laminoplasty) were retrospectively studied. Inclusion criteria were as follows: CSCI without instability, spinal cord contusion in magnetic resonance image (MRI), spinal cord compression rate more than 20%, neurologic deficit American Spinal Cord Injury Association ([ASIA] scale from A to D), and follow-up of at least 12 months. Preoperative neurological state, clinical outcome, and neurological function were measured using the ASIA impairment scale, Japanese Orthopaedic Association (JOA) grading scale, and Hirabayashi recovering rate, respectively. RESULTS: Thirty-three (80.4%) patients showed improvement in ASIA grade at 12-month follow-up. Four (9.7%) patients in ASIA Grade A and 4 (9.7%) patients in ASIA Grade D remain unchanged. The mean JOA score improved from 8.4 +/- 6.1 points preoperatively to 11.2 +/- 5.4 points at 12 months postoperatively. Improvement in JOA was statistically significant (P < 0.05). The mean Hirabayashi recovery rate was 37.4 +/- 25.3%. CONCLUSION: Surgical decompression (laminoplasty) is helpful in relieving cord compromise and neurological deficit in CSCI with stable spine. PMID- 27366258 TI - Comparison of the frequency of psychiatric disorders among patients with chronic low back pain and control group. AB - BACKGROUND: Low back pain (LBP) is one of the most common complaints of patients referred to the clinics. Studies indicated that psychosocial factors have great impact on the patients' complaints and disability. The aim of this study was to evaluate a broad range of psychiatric disorders in patients with chronic LBP (CLBP) and compare them with those of the control group. PATIENTS AND METHODS: We applied Symptom Checklist 90-R to compare 50 CLBP patients in the case group with 100 participants without it in the control group. The questionnaire measured somatization, obsessive-compulsive disorder, depression, anxiety, phobic anxiety, hostility, interpersonal sensitivity, paranoid ideation, and psychoticism. RESULTS: Average "global severity index" was 1.10 in the case and 0.5 in the control group. Average "positive symptom total" was 45.26 in the case and 27.41 in the control group. Average "positive symptom distress index" was 2.50 in the case and 1.50 in the control group. Average scores for all test dimensions were significantly different between the two groups (P = 0.00). CONCLUSIONS: All dimensions were significantly more common in CLBP patients. Therefore, early diagnosis and treatment of these disorders may improve the outcome of CLBP. PMID- 27366259 TI - Interhemispheric transcallosal transforaminal approach and its variants to colloid cyst of third ventricle: Technical issues based on a single institutional experience of 297 cases. AB - CONTEXT: Colloid cysts are benign intracranial lesions that usually involve the anterior third ventricle with varying appearance on imaging studies. The number of articles debating the origin of this tumor is surpassed by papers proposing the best modality available for its treatment. AIM: The purpose of this study is to analyze the clinical presentation and surgical outcome of colloid cysts surgically managed over a period of thirty-two years and evaluate the technical issues based on our experience. STUDY DESIGN: This is a retrospective case series study. MATERIALS AND METHODS: This is a retrospective case series study on 297 consecutive patients with colloid cysts who were operated. The case records of all the patients were evaluated to record the clinical symptoms and signs, imaging findings, surgical procedure, complications and follow-up data. RESULTS: There were 178 (60%) males and 119 (40%) females, their age ranging from 9 to 66 years with a mean age of 28 years. The mean duration of symptoms was 1.8 months. Raised intracranial pressure headache was the most common initial presenting symptom followed by visual blurring, memory disturbance and drop attacks with gait unsteadiness. The tumor was an incidental imaging finding in five patients (2%). While an interhemispheric transcallosal approach was used in 275 (92.6%) patients, it was trans-cortical in 22 (7.4%). Twenty-two patients required emergency surgery in view of worsening sensorium. Postoperative complications included memory impairment, limb weakness and seizures. Despite documented complete excision of the tumor in 6 cases, 8 patients had recurrence of tumor during follow-up. CONCLUSION: Colloid cysts are potential life threatening but benign lesions that can be removed safely with low morbidity and mortality through the interhemispheric transcallosal approach and its variants. The possibility for recurrence warrants, close imaging follow-up after surgery. It is essential for neurosurgeons to be familiar with the different transcallosal approaches to reach the third ventricle especially for a posteriorly situated cyst and a narrow foramen of Munro. PMID- 27366260 TI - Usefulness of navigated O-arm((r)) in a teaching center for spinal trauma. AB - BACKGROUND: There is a relatively high incidence of screw misplacement during spinal instrumentation due to distortion of normal anatomy following spinal trauma. AIMS AND OBJECTIVES: To evaluate and share the initial experience with the use of neuro-navigated 3D O-arm((r)) (Medtronic, USA) as compared to traditional 2D fluoroscopy in atrauma center in India. MATERIALS AND METHODS: In this retrospective study, consecutive patients of spinal injury who underwent screw fixation under O-arm guidance over nine-month period (July 2010 till March 2011) were evaluated for accuracy of screw placement. An equal number of consecutive patients prior to March 2011 who underwent screw fixation in 2D fluoroscopy were included for comparison. Patient demographics and radiology were reviewed and spinal injury was assessed using the ASIA grading in both the groups. Screw placement was assessed by postoperative CT scans of the relevant spine and accuracy of screw placement and breach of the medial or lateral cortex of the pedicle were recorded for each case. RESULTS: In the O-arm group, there were 57 patients in whom 210 screws were inserted. None of the patients had screw mal-placement. In 2D fluoroscopy group, 57 patients had 268 screws insertions. 10 (3.73%) screws were found to be malpositioned in the postoperative CT scans (8 in thoracic spine and 2 in odontoid fractures). The malposition rate was highly significant in 2D fluoroscopy thoracolumbar (P = 0.0015) subgroup. One patient had neurological deterioration and three patients required repositioning of the screws. CONCLUSION: In a teaching center with multiple surgeons, the O-arm((r)) imaging ensures accurate placement of screws as compared to traditional 2D fluoroscopy. PMID- 27366262 TI - Tectal lipoma presenting with headache: An unusual etiology! PMID- 27366261 TI - Fenestrated optic nerve in craniopharyngioma. PMID- 27366263 TI - Revealing the hidden: Delight of susceptibility weighted imaging for neurosurgeons! PMID- 27366264 TI - Decompressive laminectomy for thoracic ossification of the posterior longitudinal ligament. PMID- 27366265 TI - Good outcome after delayed surgery for orbitocranial non-missile penetrating brain injury. AB - Nonmissile orbitocranial penetrating brain injuries are uncommonly dealt with in a civilian context. Surgical management is controversial, due to the lack of widely accepted guidelines. A 52-year-old man was hit in his left eye by a metallic foreign body (FB). Head computed tomography (CT) scan showed a left subcortical parietal FB with a considerable hemorrhagic trail originating from the left orbital roof. Surgical treatment was staged; an exenteratio oculi and a left parietal craniotomy to extract the FB under intraoperative CT guidance were performed at post trauma day third and sixth, respectively. A postoperative infectious complication was treated conservatively. The patient retained a right hemiparesis (3/5) and was transferred to rehabilitation in good clinical conditions at day 49(th). He had suspended antiepilectic therapy at that time. A case-by-case tailored approach is mandatory to achieve the best outcome in such a heterogeneous nosological entity. Case reporting is crucial to further understand its mechanism and dynamics. PMID- 27366266 TI - Tension pneumocephalus causing brain herniation after endoscopic sinus surgery. AB - Endoscopic sinus surgery (ESS) may rarely be complicated by intracranial complications; the most common of them is a cerebrospinal fluid fistula. Pneumocephalus as a complication of ESS is quite rare. Here, we presented a unique case of tension pneumocephalus causing brain herniation as a complication of ESS, to whom emergent craniotomy was performed. PMID- 27366267 TI - Supratentorial endodermal cysts - Report of two cases. AB - We describe two rare cases of frontal cystic lesions presenting with symptoms and signs of raised intracranial pressure. Both had a preoperative diagnosis of an arachnoid cyst and were subjected to a craniotomy with marsupialization of the cyst. However, the histology confirmed them to be an endodermal cyst (EC) on both occasions. Both the patients have been closely followed with no recurrence of symptoms. ECs of the central nervous system are usually reported in the spinal canal, mid-line posterior fossa, and the suprasellar regions. Supratentorial and non-midline ECs are rare, with only about 22 cases previously reported in literature. We discuss both the cases and review the relevant literature. PMID- 27366268 TI - Acute obstructive hydrocephalus complicating decompression surgery of the craniovertebral junction. AB - Obstructive hydrocephalus has been described as a rare complication following foramen magnum decompression for Chiari malformation. However, there are few reports of obstructive hydrocephalus after spinal surgery for other pathologies of the craniovertebral junction (CVJ). The authors herein report a 52-year-old female with achondroplasia presenting with an 8-month history of myelopathy due to spinal cord compression at CVJ. She underwent resection of the C1 posterior arch and part of the edge of the occipital bone. A computed tomography (CT) scan obtained 1-week after the surgery revealed bilateral infratentorial fluid collection. The patient was first managed conservatively; however, on the 17(th) day, her consciousness level showed sudden deterioration. Emergency CT demonstrated marked hydrocephalus due to obstruction of the cerebral aqueduct. Acute obstructive hydrocephalus can occur late after decompression surgery at the CVJ, and thus should be included in the differential diagnosis of a deteriorating mental status. PMID- 27366269 TI - Cerebellospinal hemangioblastoma with bilateral pheochromocytoma and hepatic cyst: A rare entity. AB - A 45-year-old gentleman presented with headache, dizziness, and unsteadiness of gait. On imaging, he was found to have a cerebellar and a spinal intramedullary hemangioblastoma. To rule out Von Hippel-Lindau (VHL) disease, we did screening of the whole abdomen with ultrasonography followed by contrast-enhanced computed tomography of the abdomen, and surprisingly, the patient was having bilateral adrenal pheochromocytoma and a hepatic cyst. A diagnosis of VHL disease was made on this basis. The patient was operated and he made a very good recovery. We are reporting this interesting case because of its typical findings and its rarity. Disease management and review of literature were also discussed at the end. PMID- 27366270 TI - Aneurysm of azygos anterior cerebral artery: A report of two cases. AB - Aneurysms of azygos anterior cerebral artery (ACA) are rare with very few cases reported in medical literature. We report here two cases of aneurysm of azygos ACA among 105 patients with subarachnoid hemorrhage. The two aneurysms were successfully clipped by using the bifrontal basal interhemispheric approach. PMID- 27366271 TI - Transformation of a meningioma with atypical imaging. AB - Meningiomas are benign tumors of the central nervous system. They have long term curability if they are excised completely. If not, they can recur after a prolonged period and can lead to increased morbidity during re-surgery. Recurrence is rarely associated with invasiveness. Usually de-differentiation in case of meningiomas is uncommon without any predisposing factors including different genetic mutations or radiation to the involved region. We report a case of a 38-year-old female who was operated for a benign para-sagittal meningioma 8 years back and subsequently developed an invasive recurrence off late. Also this time, the imaging morphology was slightly different for a meningioma and gross as well as microscopic findings were very atypical. Awareness for such cases must be there while dealing with recurrent meningiomas as invasiveness may not always be associated with adverse predisposing factors like radiation. As invasiveness is always a histopathological diagnosis, picking up such features on imaging is a daunting task and if done, can help neurosurgeons prognosticate such invasive recurrences in a better fashion. PMID- 27366272 TI - Esthesioneuroblastoma with intracranial extension: A non-surgical approach. AB - Esthesioneuroblastoma is a rare tumor arising from the olfactory mucosa of upper respiratory tract. The primary modality of treatment has been surgery with craniofacial resection followed by post-operative radiotherapy. There are only a few reported cases of non-surgical approaches. We report a case of esthesioneuroblastoma with intracranial extension treated with Vincristine, Adriamycin, Cyclophosphamide, Ifosfamide, Etoposide protocol followed by radiation with 5 years of follow-up. This is the first reported case using this chemotherapy schedule. PMID- 27366273 TI - Malignant metastatic carcinoid presenting as brain tumor. AB - Carcinoid tumors are rarely known to metastasise to the brain. It is even more rare for such patients to present with symptoms related to metastases as the initial and only symptom. We present a case of a 60-year-old man who presented with hemiparesis and imaging features suggestive of brain tumor. He underwent surgery and the histopathology revealed metastatic malignant lesion of neuroendocrine origin. A subsequent work up for the primary was negative. Patient was treated with adjuvant radiotherapy. We present this case to highlight the pathophysiological features, workup and treatment options of this rare disease and discuss the methods of differentiating it from more common brain tumors. PMID- 27366274 TI - Delayed supratentorial intracerebral hemorrhage following posterior fossa surgery. AB - Delayed supratentorial intracerebral hematoma after posterior fossa surgery is uncommon. Only few cases have been reported in the past. The cause has been attributed to sitting position leading to changes in intracranial arterial and venous pressures. We report two cases of delayed intracerebral hematoma following posterior fossa surgery, none of which were operated in sitting position. MR venogram done in one patient showed venous sinus thrombosis. Intracererbal hematoma following infratentorial surgery is uncommon and is possibly due to venous sinus thrombosis leading to venous hypertension. Control of bleeding from venous sinuses due to avulsion of emissary veins during craniotomy/craniectomy possibly induces sinus thrombosis that may propagate antegrade or retrograde, leading to venous hypertension and parenchymal bleed. PMID- 27366275 TI - Medullomyoblastoma: A rare case in an unusual location in an atypical age group. AB - Medullomyoblastoma is a variant of medulloblastoma with an aggressive course. It is typically seen in children less than 10 years of age and usually arises from the cerebellar vermis. Authors report an unusual case of medullomyoblastoma arising from the right middle cerebellar peduncle in an adult patient and pertinent literature is reviewed regarding this uncommon entity. PMID- 27366276 TI - 'Subarachnoid cyst' after evacuation of chronic subdural hematoma: Case report of an unusual postoperative morbidity. AB - Burr-hole drainage of chronic subdural hematomas are routine operative procedures done by neurosurgical residents. Common postoperative complications include acute epidural and/or subdural bleeding, tension pneumocephalus, intracranial hematomas and ischemic cerebral infarction. We report an interesting post-operative complication of a 'subarachnoid cyst' after burr-hole evacuation of a chronic subdural hematoma. The authors hypothesize that the 'cyst' is likely secondary to the splitting of the adjacent neomembrane within its arachnoid-brain interface by iatrogenic irrigation of the subdural space. Over time, this 'cyst' develops into an area of gliosis which eventually causes long-term scar epilepsy in the patient. As far as we are aware, this is the first complication of such a 'subarachnoid cyst' post burr-hole drainage reported in the literature. PMID- 27366277 TI - Lethal penetrating stab injury to the vertebral artery: A case report with review of literature. AB - The vertebral arteries are rarely injured in penetrating neck trauma due to their deep location in the foramen transversarium. These injuries in isolation are not associated with neurological deficits or ischemic changes on radiology as the collaterals are usually sufficient. We report a case of fatal unilateral vertebral artery stab injury leading to bilateral cerebellar and brainstem infarction. The carotid Doppler ruled out the presence of any carotid artery injury. Life-threatening injuries are possible in the presence of hypoplastic contralateral vertebral artery or inadequate flow from the anterior circulation not making up for the deficit. This emphasizes that thorough evaluation and timely management of suspected injuries to even a single vertebral artery should be undertaken. PMID- 27366278 TI - Non psammomatous melanocytic schwannoma presenting as a subcutaneous nodule: A rare presentation of a rare lesion. AB - Melanocytic schwannoma (MS) is an extremely rare soft tissue tumor accounting for less than 1% of all primitive nerve sheath tumors, with a predilection for spinal nerve involvement. To date, only 20 cases of cutaneous/subcutaneous MS have been described in literature. Here, we describe a case of MS presenting as a subcutaneous nodule in a 22-year-old male in right thigh. On examination, the nodule measured 2.5 * 2.0 * 1.5 cm with overlying skin showing a bluish hue and an ulcer. With a preoperative diagnosis of hemangioma, the patient was taken up for wide local excision and was diagnosed as a case of non psammomatous melanocytic schwannoma based on clinical, histological, and immunohistochemical studies. Immunohistochemistry revealed positivity with S-100, HMB-45, and Melan A with pericellular Laminin positivity. Carney's syndrome was ruled out. MS needs to be differentiated from other pigmented lesions like pigmented neurofibroma, Bednar tumor, cellular blue neavus, and especially malignant melanoma, which has an obvious ominous prognosis. Since MS can show unpredictable behavior especially in absence of overt malignant features, a long term follow up with or without radiotherapy is recommended. PMID- 27366279 TI - Development of contralateral extradural hematomas after evacuation of primary one. AB - The occurrence of bilateral extradural hematomas (EDH) is an uncommon consequence of closed head injuries. Incidence of bilateral EDH has been reported in various studies ranging from 2 to 25%. Bilateral EDH may develop simultaneously or second EDH develops few hours after first one. Development of second EDH after evacuation of primary one is rarely seen. We are reporting one such case. Awareness of this entity is required to detect such cases as timely intervention gives an excellent result like an acute EDH. PMID- 27366280 TI - Pleomorphic xanthoastrocytoma with anaplastic features: A rare case report and review of literature with reference to current management. AB - Pleomorphic xanthoastrocytoma (PXA) is an uncommon tumor constitutes less than 1% of all astrocytic glial neoplasms was first reported in 1979. PXA commonly occurs in young patients and manifests itself first as seizures followed by focal neurological deficits. The role of radiotherapy or chemotherapy has not yet been established because of the relative infrequency of this disease. PXA is classified as grade II tumor in the WHO classification of tumors of the CNS. In literature 9 to 20 % PXA may undergo malignant change at recurrence or may display at the time of initial presentation. Malignant transformation is mainly associated with high mitotic activity and necrosis. The criteria for PXA with anaplastic features was five or more mitotic activity per 10 high power fields, necrosis, microvascular proliferation, marked cellular anaplasia, and high Ki-67 labeling indices. PXA with anaplastic features management is highly controversial as very sparse literature is available. We are reporting a case of PXA with anaplastic features with atypical radiology and tried to review the up to date literature regarding this rare tumor. PMID- 27366282 TI - Supratentorial metastasis of medulloblastoma in adults. AB - Two adults, 31 and 20 years of age, developed supratentorial metastasis 31/2 years and 11 months, respectively, after gross total removal of their posterior fossa medulloblastoma. The first case developed spinal metastasis as well. Both had undergone craniospinal irradiation. Case 1 underwent laminectomy and case 2 underwent craniotomy because their presenting symptoms required so. PMID- 27366281 TI - Glioblastoma with signet ring cell morphology: A diagnostic challenge. AB - Glioblastoma (WHO Grade IV), the most frequent malignant brain tumor, can have varied morphologic variations like epithelial/glandular structures, granular cells, and lipidized cells. Glioblastoma with signet ring cell morphology is very unusual and can mimic a metastatic carcinoma. These rare tumors may be just a morphological variant or may signify a different carcinogenic pathway. PMID- 27366283 TI - Transorbital penetrating brain injury by a wooden stick: A neuro-ophthalmologic emergency. AB - Accidental penetrating brain injury through transorbital route is an unusual occurrence in emergency practice of civilian cases. At time, it could be potentially life threatening. We report an interesting case of transorbital penetrating brain injury with a wooden stick in a 44-year-old male epileptic patient. The stick was removed successfully through transorbital exploration, without any neurovascular complications. The pertinent literature is reviewed and emergent management of such cases is discussed. PMID- 27366284 TI - Tiger hide appearance: Impaction and prolapse of brain parenchyma through burr holes after evacuation of bilateral chronic subdural hematoma: A rare case report. AB - Burr hole evacuation of chronic subdural hematoma (SDH) with or without drainage system is the most common surgical method among various techniques. There are various complications of burr hole drainage evacuation of chronic SDH, but there is no case report regarding impaction and prolapse of brain parenchyma through burr hole as a complication. Herewith, we are reporting a case of bilateral chronic SDH with prolapse of brain parenchyma through burr holes. Magnetic resonance imaging (MRI) of brain showed a characteristic look and we named it "Tiger hide appearance". We failed to find such characteristic appearance in MRI brain on reviewing the available literature. PMID- 27366285 TI - Subdural hydatid cyst presenting as recurrent subdural hygroma. AB - Intracranial hydatid disease is an uncommon entity that usually is parenchymal in location. Presence of hydatid cyst in subdural location is being reported for the first time in the literature. A 13-year-old female child with the diagnosis of hydatid disease of brain was operated. She was advised to take albendazole which she did not take. In postoperative period she developed recurrent subdural hygroma for which multiple surgical interventions were done and finally cause of recurrent subdural hygroma was found to be hydatid cyst in the subdural space. The patient had initially undergone craniotomy for the excision of hydatid cyst. Later on she developed subdural hygroma for which the burr hole drainage was done twice. At time of third recurrence subduro-peritoneal (SDP) shunt was done. When she had recurrence again along with hydrocephalus, than VP shunt and revision of the SDP shunt was planned. While doing revision of SDP shunt, hydatid cyst was seen emerging from the burr hole site. A craniotomy was done to remove the hydatid cyst from the subdural space. Since then there has been no recurrent collection. Complete surgical excision is the best treatment modality to treat hydatid cyst of brain. Accidental spillage of the contents can have lead to recurrence, so every effort must be taken to prevent spillage of contents. Postoperatively all the patients must be put on antihelminthics. PMID- 27366286 TI - Intradural teratoma in a neonate with meningomyelocele. AB - Meningomyelocele is a common congenital problem. The teratoma is a neoplasm composed of tissues foreign to the part in which they arise. An intradural teratoma within a meningomyelocele is a very rare association. We report a case of intradural teratoma with a brief review of the relevant literature. PMID- 27366287 TI - Parietal pilomyxoid astrocytoma with recurrence in 10 months: A case report and review of literature. AB - Pilomyxoid astrocytoma (PMA) is a new entity described in WHO 2007 classification of brain tumors. Pilocytic astrocytoma (PA) and PMA share many histopathological features with a few differences in histopathology and behavior of the tumor. This tumor is commonly located in the hypothalamic chiasmatic region. PMA behaves more aggressively than PA, with shorter progression-free survival as well as a higher rate of recurrence and CNS dissemination. We describe a case of PMA in a 10-year old male involving left parietal lobe presenting with raised ICP features along with the follow-up. Patient was symptom free after 7 months of postoperative and 51/2 months of post-radiation. The unusual site and atypical Magnetic resonance imaging features are distinctive in this case report. PMID- 27366288 TI - [Simultaneous rupture of the anterior cruciate ligament and the patellar tendon: a case report]. AB - Simultaneous rupture of both the patellar tendon and the anterior cruciate ligament is a relatively rare injury. Its diagnosis can easily be missed during the initial examination. Treatment options include immediate repair of the patellar tendon with either simultaneous or delayed reconstruction of the ACL. We present the case of a combined rupture of the patellar tendon, the anterior cruciate ligament in a 22-year old footballer. A two-stage treatment approach was performed with an excellent functional outcome. PMID- 27366289 TI - An Overview of Zika Virus Disease. PMID- 27366290 TI - The Utility of Quantifiable Neurologic Assessments After Stroke: In response to Marsh et al, "The NIH Stroke Scale Has Limited Utility in Accurate Daily Monitoring of Neurologic Status". PMID- 27366291 TI - The NIH Stroke Scale Has Limited Utility in Accurate Daily Monitoring of Neurologic Status. AB - BACKGROUND AND PURPOSE: The National Institute of Health Stroke Scale (NIHSS) is rapid and reproducible, a seemingly attractive metric for the documentation of clinical progress in patients presenting with ischemic stroke. Many institutions have adopted it into daily clinical practice. Unfortunately, the scale may not adequately capture all forms of functional change. We evaluate its utility as a measure of recovery in patients treated with intravenous tissue plasminogen activator (IV tPA) for ischemic stroke. METHODS: We prospectively evaluated the difference in the rate of improvement based on NIHSS (a >=4 point change based on previous trials) versus physician-documented subjective and objective measures in 41 patients' status post IV tPA treatment. The NIHSS 24 hours posttreatment, on discharge, and at follow-up were compared to NIHSS on admission using tests of proportions and McNemar tests of paired data. Secondary analyses were performed defining significant improvement as NIHSS changes of 1 to 3 points. RESULTS: The mean NIHSS improved from 9 to 6, 24 hours post-tPA. Of the 41 patients, 29 improved by physician documentation, although only 11 of the 29 met the NIHSS criteria (P < .001; McNemar P < .001). On discharge, 20 of the 41 patients met the NIHSS criteria; however, the proportion "better" by physician documentation (71%) remained significantly higher (P = .04; McNemar P = .004). The mean postdischarge follow-up NIHSS was 2. Twenty of the 21 patients improved by documentation versus 16 of the 21 by NIHSS (P = .08, McNemar P = .125). Using NIHSS changes of 1 to 3 increased sensitivity for detecting improvement but remained lower than physician documentation. CONCLUSION: The NIHSS has many advantages; however, it may miss functional changes when used in place of a comprehensive neurological examination to measure improvement poststroke. PMID- 27366292 TI - The Itemized NIHSS Scores Are Associated With Discharge Disposition in Patients With Minor Stroke. AB - BACKGROUND AND PURPOSE: The ability of the National Institutes of Health Stroke Scale (NIHSS) score to predict functional outcome in minor stroke is controversial. In this study, we examined the association of itemized NIHSS score with discharge outcome. METHODS: We included all patients with final diagnosis of stroke with an NIHSS score of 0 to 5 untreated with thrombolysis enrolled in the "Stroke Warning Information and Faster Treatment" trial. Individual components of the NIHSS score were the primary predictors. Poor outcome was defined as not being discharged home. Logistic regression was used to identify predictors of outcome. RESULTS: A total of 861 patients met the inclusion criteria; 162 (19%) were not discharged home. In multivariable regression, predictors of discharge other than home were age (odds ratio [OR] = 1.02 per year increase, P < .001) and total NIHSS score (OR per unit increase in the NIHSS = 1.51, P < .001). Motor (OR = 2.32, P < .001), level of consciousness (LOC; OR = 6.62, P = .004), and ataxia (OR = 3.10, P < .001) were also associated with not being discharged home. Motor (area under the curve [AUC] 0.623) appeared to be more predictive of poor outcome than ataxia (AUC 0.569) and LOC (AUC 0.517). The total NIHSS had a fair correlation with discharge outcome (AUC 0.683). CONCLUSION: Total and itemized NIHSS components have a fair correlation with outcome in minor stroke highlighting the importance of other measures of stroke severity for clinical trials. PMID- 27366293 TI - The Influence of Language Discordance Between Patient and Physician on Time-to Thrombolysis in Acute Ischemic Stroke. AB - BACKGROUND AND PURPOSE: Reducing door-to-imaging (DIT) time is a major focus of acute stroke quality improvement initiatives to promote rapid thrombolysis. However, recent data suggest that the imaging-to-needle (ITN) time is a greater source of treatment delay. We hypothesized that language discordance between physician and patient would contribute to prolonged ITN time, as rapidly taking a history and confirming last known well require facile communication between physician and patient. METHODS: This is a retrospective analysis of all patients who received tissue plasminogen activator (tPA) in our emergency department between July 2011 and December 2014. Baseline characteristics and relevant time intervals were compared between encounters where the treating neurologist and patient spoke the same language (concordant cases) and where they did not (discordant cases). RESULTS: A total of 279 patients received tPA during the study period. English was the primary language for 51%, Spanish for 46%, and other languages for 3%; 59% of cases were classified as language concordant and 41% as discordant. We found no differences in median DIT (24 vs 25, P = .5), ITN time (33 vs 30, P = .3), or door-to-needle time (DTN; 58 vs 55, P = .1) between concordant and discordant groups. Similarly, among patients with the fastest and slowest ITN times, there were no differences. CONCLUSION: In a high-volume stroke center with a large proportion of Spanish speakers, language discordance was not associated with changes in DIT, ITN time, or DTN time. PMID- 27366294 TI - Magnesium for Treatment of Reversible Cerebral Vasoconstriction Syndrome: Case Series. AB - We describe 2 cases of reversible cerebral vasoconstriction syndrome (RCVS) with refractory headache aborted by intravenous magnesium. Case 1 is a 53-year-old woman with subarachnoid hemorrhage due to RCVS presented with refractory headache and persistent vasospasm, despite aggressive treatment with calcium channel blockers (CCBs) and systemic corticosteroids. Subsequently, she experienced dramatic relief of symptoms with intravenous magnesium therapy. She continued oral maintenance therapy and remained symptom free. Case 2 is a 71-year-old female with bilateral temporo-occipital infarcts due to RCVS, presented with refractory headache and persistent vasospasm on transcranial Doppler (TCD), despite aggressive treatment with CCBs. She experienced dramatic relief of symptoms with intravenous magnesium and resolution of vasospasm on TCD. Magnesium may be beneficial for the treatment of refractory headaches in patients with RCVS. Future studies are needed to determine whether it should be considered as a first-line agent. PMID- 27366295 TI - A Case of Complex PFO Leading to Ischemic Stroke: A Practical Clinical Pearl for Neurohospitalists. AB - Patent foramen ovale (PFO) has been proposed as a mechanism for cardioembolic stroke, especially in younger patient populations. Complex PFOs, with tunnel lengths exceeding 8 mm, lead to a higher risk of neurological sequelae than simple PFOs and may also be harder to detect with transthoracic echocardiography (TTE). In this article, we present a 29-year-old woman who, after polypharmacy overdose, developed deep venous thrombosis and multiple pulmonary emboli (PE) and subsequent cardioembolic stroke. Initial TTE showed intact interatrial septum with late appearance of agitated saline in the left atrium after the seventh cardiac cycle. Subsequent transesophageal echocardiography, after treatment of PE with an intravenous thrombolytic (alteplase) and anticoagulation with heparin, showed a complex PFO with a 19-mm overlap of the septum primum and secundum without active flow. It is suggested that this PFO allowed for flow only in the situation of elevated right heart strain with PE, causing cardioembolic stroke and detection of agitated saline in the left atrium on TTE. However, under normal physiological situations, which resumed after treatment of PE with alteplase and heparin, the PFO did not allow for flow. This case demonstrates the potential importance of recognition of complex PFOs in diagnosis and management of cardioembolic stroke. PMID- 27366296 TI - Heparin Resistance and Anticoagulation Failure in a Challenging Case of Cerebral Venous Sinus Thrombosis. AB - We report a challenging case of cerebral venous sinus thrombosis (multiple etiologic factors) that was complicated by heparin resistance secondary to suspected antithrombin III (ATIII) deficiency. A 20-year-old female previously healthy and currently 8 weeks pregnant presented with worsening headaches, nausea, and decreasing Glasgow Coma Scale/Score (GCS), necessitating mechanical ventilatory support. Imaging showed extensive clots in multiple cerebral venous sinuses including the superior sagittal sinus, transverse, sigmoid, jugular veins, and the straight sinus. She was started on systemic anticoagulation and underwent mechanical clot removal and catheter-directed endovascular thrombolysis with limited success. Complicating the intensive care unit care was the development of heparin resistance, with an inability to reach the target partial thomboplastin time (PTT) of 60 to 80 seconds. At her peak heparin dose, she was receiving >35 000 units/24 h, and her PTT was subtherapeutic at <50 seconds. Deficiency of ATIII was suspected as a possible etiology of her heparin resistance. Fresh frozen plasma was administered for ATIII level repletion. Given her high thrombogenic risk and challenges with conventional anticoagulation regimens, we transitioned to argatroban for systemic anticoagulation. Heparin produces its major anticoagulant effect by inactivating thrombin and factor X through an AT-dependent mechanism. For inhibition of thrombin, heparin must bind to both the coagulation enzyme and the AT. A deficiency of AT leads to a hypercoagulable state and decreased efficacy of heparin that places patients at high risk of thromboembolism. Heparin resistance, especially in the setting of critical illness, should raise the index of suspicion for AT deficiency. Argatroban is an alternate agent for systemic anticoagulation in the setting of heparin resistance. PMID- 27366298 TI - Chorea as the Neurological Symptom of Delayed Encephalopathy After Carbon Monoxide Intoxication in a Child. PMID- 27366297 TI - Management of Acute Hypertensive Response in Patients With Ischemic Stroke. AB - High blood pressure (BP) >140/90 mm Hg is seen in 75% of patients with acute ischemic stroke and in 80% of patients with acute intracerebral hemorrhages and is independently associated with poor functional outcome. While BP reduction in patients with chronic hypertension remains one of the most important factors in primary and secondary stroke prevention, the proper management strategy for acute hypertensive response within the first 72 hours of acute ischemic stroke has been a matter of debate. Recent guidelines recommend clinical trials to ascertain whether antihypertensive therapy in the acute phase of stroke is beneficial. This review summarizes the current data on acute hypertensive response or elevated BP management during the first 72 hours after an acute ischemic stroke. Based on the potential deleterious effect of lowering BP observed in some clinical trials in patients with acute ischemic stroke and because of the lack of convincing evidence to support acute BP lowering in those situations, aggressive BP reduction in patients presenting with acute ischemic stroke is currently not recommended. While the early use of angiotensin receptor antagonists may help reduce cardiovascular events, this benefit is not necessarily related to BP reduction. PMID- 27366299 TI - Thunderclap Headache Secondary to Pneumocephalus Following Epidural Anesthesia. PMID- 27366300 TI - Diagnosing RCVS Without the CV: The Evolution of Reversible Cerebral Vasoconstriction Syndrome. AB - This is a case of a 52-year-old man with a past medical history of 2 episodes of coital thunderclap headaches as well as recent cocaine, marijuana, and pseudoephedrine use, who presented with sudden, sharp, posterior headache associated with photophobia and phonophobia. His initial magnetic resonance imaging (MRI) of the brain, magnetic resonance angiography (MRA) of the head, and magnetic resonance venography (MRV) of the head were all normal as well as a normal lumbar puncture. Given the multiple risk factors for reversible cerebral vasoconstriction syndrome (RCVS), the patient was treated for suspected RCVS, despite the normal imaging. Repeat MRI brain 3 days after hospital admission demonstrated confluent white matter T2 hyperintensities most prominent in the occipital lobes, typical of posterior reversible encephalopathy syndrome (PRES). Repeat MRA of the head 1 day after discharge and 4 days after the abnormal MRI brain showed multisegment narrowing of multiple arteries. This case demonstrates that RCVS may present with PRES on MRI brain and also exemplifies the need to treat suspected RCVS even if imaging is normal, as abnormalities in both the MRI and the MRA may be delayed. PMID- 27366301 TI - Quality of life after liver transplantation: State of the art. AB - Quality of life (QoL) after deceased donor liver transplantation is increasingly recognized as a major outcome parameter. We reviewed recent publications in this rapidly evolving field in order to summarize recent achievements in the field and to define opportunities and perspectives for research and improvement of patient care. QoL does improve after liver transplantation according to a typical pattern. During the first year, there is a significant improvement in QoL. After one year, the improvement does stabilise and tends to decline slightly. In addition to the physical condition, different psychological parameters (such as depression, anxiety, sexual function) and sociodemographic elements (professional state, sex, marital state) seem to impact QoL. Opportunities for further research are the use of dedicated questionnaires and identification of influencing factors for QoL. PMID- 27366302 TI - Clinical characteristics and progression of liver abscess caused by toxocara. AB - AIM: To evaluate the clinical characteristics and progression of liver abscess caused by toxocara. METHODS: We retrospectively reviewed the medical records of patients with serum IgG antibody to Toxocara canis and liver abscess diagnosed using abdominal computed tomography between February 2010 and February 2015. Among 84 patients exhibiting serum IgG antibody to Toxocara canis, 34 patients were diagnosed with liver asbscess and treated with albendazole. A follow-up period of 1 year was conducted. RESULTS: Mean patient age was 53 (34-79) years, with 26 (76.5%) patients being male. Twenty-one (61.7%) patients were moderate or heavy drinkers, 23 (67.6%) patients had a history of eating raw meat or liver and 6 (17.6%) patients owned pet dogs or cats. Main patient symptoms consisted of right upper quadrant pain, fever, and fatigue; 18 (52.9%) patients, however, presented with no symptoms. Lung involvement was detected in 444 (11.7%) patients. The eosinophil count increased in 29 (85.3%) patients at initial diagnosis, and decreased in most patients after albendazole treatment. The initial serum IgE level increased in 25 (73.5%) patients, but exhibited various response levels after albendazole treatment. Liver abscess formation improved in all patients. CONCLUSION: The liver abscess was improved with albendazole treatment. PMID- 27366303 TI - Treating chronic hepatitis B virus: Chinese physicians' awareness of the 2010 guidelines. AB - AIM: To investigate Chinese physicians' awareness of the 2010 guidelines on the treatment of chronic hepatitis B virus (HBV) infection. METHODS: This was a quantitative survey that investigated the characteristics and practices of physicians who were treating patients with hepatitis B, the profile of their patients and physician practices regarding the diagnosis and treatment of HBV at the time of the survey. Participants were randomly selected from available databases of Chinese physicians and requested to complete either an online or paper-based survey. Data from the survey responses were analysed. For data validation and interpretation, qualitative indepth interviews were conducted with 39 of the respondents. RESULTS: Five-hundred completed surveys, from 663 physicians were available for analysis. A mean of 175 chronic hepatitis B (CHB) patients was seen by each physician every month, of whom 85 (49%) were treated in line with therapeutic indications stated in the 2010 guidelines. A total of 444 (89%) physicians often (> 60% of the time) adhered to the guidelines. Most physicians used antiviral medications as recommended. For patients with compensated and decompensated cirrhosis, 342 (68%) and 336 (67%) of physicians, respectively, often followed the recommendation to use potent nucleos(t)ide analogues with a high genetic barrier to resistance, using the appropriate treatment more than 60% of the time. Physicians from infectious disease or liver disease departments were better informed than those from gastrointestinal or other departments. CONCLUSION: The majority of Chinese physicians often adhere to Chinese 2010 CHB guidelines and are well-informed about the use of antiviral medications for hepatitis B. PMID- 27366304 TI - Transarterial radioembolization vs chemoembolization for hepatocarcinoma patients: A systematic review and meta-analysis. AB - AIM: To compare the efficacy and safety of yttrium-90 radioembolization (Y90RE) and transarterial chemoembolization (TACE) in hepatocellular carcinoma patients. METHODS: Bibliographic research was conducted on main scientific databases. When there was no statistically significant heterogeneity, pooled effects were calculated using a fixed-effects model by means of Mantel-Haenszel test, otherwise, a random-effects model was used with DerSimonian and Laird test. Summary estimates were expressed in terms of odds ratios (ORs) and 95%CI. The probability of publication bias was assessed using funnel plots and with Begg and Mazumdar's test. Sensitivity analysis was finally conducted using the method of excluding extreme data. RESULTS: A total of 10 studies were analyzed, of which 2 randomized controlled trials. Survival rate (SR) assessed at 1 year showed an absolute similarity between the two treatment groups (OR = 1.01, 95%CI: 0.78 1.31, P = 0.93). As long as time elapsed since the treatment, ORs for survival rate tended to significantly increase, thus meaning better long-term outcomes in patients who underwent Y90RE (2-year SR: OR = 1.43, 1.08-1.89, P = 0.01; 3-year SR: OR = 1.48, 1.03-2.13, P = 0.04). Meta-analysis of plotted hazard ratios (HRs) determined a non-significant overall estimate in favor of Y90RE (HR = 0.91, 0.80 1.04, P = 0.16). Y90RE showed a statistically significant benefit as compared to TACE in terms of higher progression-free survival rate assessed at 1 year (OR = 1.67; 95%CI: 1.10-2.55; P = 0.02). Pooled analyses do not revealed a statistically significant increase in OR for tumor objective responses after Y90RE with respect to TACE (OR = 1.22, 95%CI: 0.69-2.16, P = 0.50). A non significant trend in favor of Y90RE was observed according to adverse event rate (OR = 0.70, 0.38-1.30, P = 0.26). CONCLUSION: Our meta-analysis reveals that Y90RE and TACE show similar effects in terms of survival, response rate and safety profile, although tumor progression is delayed after radioembolization. PMID- 27366305 TI - Atypical presentation of a hepatic artery pseudoaneurysm: A case report and review of the literature. AB - Classically, hepatic artery pseudoaneurysms (HAPs) arise secondary to trauma or iatrogenic causes. With an increasing prevalence of laparoscopic procedures of the hepatobiliary system the risk of inadvertent injury to arterial vessels is increased. Pseudoaneurysm formation post injury can lead to serious consequences of rupture and subsequent hemorrhage, therefore intervention in all identified visceral pseudoaneurysms has been advocated. A variety of interventional methods have been proposed, with surgical management becoming the last step intervention when minimally invasive therapies have failed. The authors present a case of a HAP in a 56-year-old female presenting with jaundice and pruritis suggestive of a Klatskin's tumor. This presentation of HAP in a patient without any significant past medical or surgical intervention is atypical when considering that the majority of HAP cases present secondary to iatrogenic causes or trauma. Multiple minimally invasive approaches were employed in an attempt to alleviate the symptomology which included jaundice and associated inflammatory changes. Ultimately, a right hepatic trisegmentectomy was required to adequately relieve the mass effect on biliary outflow obstruction and definitively address the HAP. The presentation of a HAP masquerading as a malignancy with jaundice and pruritis, rather than the classic symptoms of abdominal pain, anemia, and melena, is unique. This presentation is only further complicated by the absent history of either trauma or instrumentation. It is important to be aware of HAPs as a potential cause of jaundice in addition to the more commonly thought of etiologies. Furthermore, given the morbidity and mortality associated with pseudoaneurysm rupture, intervention in identifiable cases, either by minimally invasive or surgical interventions, is recommended. PMID- 27366306 TI - Polymorphous Low-Grade Adenocarcinoma of the Palate: A Rare Case Report. AB - INTRODUCTION: Polymorphous low-grade adenocarcinoma (PLGA) has been known as a comparatively less aggressive malignant tumor that predominantly occurs in the minor salivary glands. It has presented as a painless, slow growing tumor in the oral cavity. It has been reported to occur rarely in the palate and the prognosis of this lesion is far better than adenocarcinoma as the regional metastasis would be very minimal. A clear difference between the biologic behaviors of adenocarcinoma and PLGA has been reported in literature. CASE PRESENTATION: A 63 year-old female reported at our institute with a swelling in relation to her upper left back region of her jaw for three months, gradual in onset and associated with pain. After clinical and radiological examination, the differential diagnosis were consolidated abscess or minor salivary gland tumor. An incisional biopsy was done and the lesion was diagnosed as PLGA. The lesion was treated by wide excision and reconstruction with immediate obturator. The post-operative follow up showed no evidence of recurrence and the healing was satisfactory. CONCLUSIONS: The site of predilection of PLGA is more in favor of palate (49 - 77.8%) followed by either upper lip or buccal mucosa (7.4 - 13.4%). There are sporadic reports of metastasis sometimes even transformation to a high grade adenocarcinoma, sometimes ending in mortality. Cervical lymph node metastasis is rare with reported incidence of 5 - 15% and is more commonly seen in recurrent tumor than the initial diseases. Extra palatal PLGAs present with significant papillary growth or arising from ventral surface of tongue frequently metastasize to cervical lymph nodes. Distant metastasis is very rare with an incidence of 7.5% and the site involved is the lung which is attributed to the inadequate control of the disease. PMID- 27366308 TI - Pancreatic Lymphangioma as a Rare Pancreatic Mass: A Case Report. AB - INTRODUCTION: Cystic lymphangiomas of abdomen has mostly involved mesentery and retro peritoneum that should be considered as a differential diagnosis of abdominal masses. Pancreatic lymphangiomas were extremely rare that should be differentiated from neoplastic pancreatic cysts. Patients have commonly presented with epigastric pain and a relevant palpable epigastric mass. CASE PRESENTATION: A 65-year-old lady who has presented with epigastric pain, then during investigations, a cystic tumor which located in the tail of pancreas, has found. Whereas definite diagnosis of tumor with routine procedures was impossible, the tumor has completely resected by distal pancreatectomy and splenectomy. Pathology and IHC was suggestive of benign lymphangioma. CONCLUSIONS: According to this presentation diagnosis of cystic lymphangioma of the tail of pancreas should be considered as a differential diagnosis of pancreatic cystic lesions and complete excision has been the treatment of choice. PMID- 27366307 TI - XRCC1 and OGG1 Gene Polymorphisms and Breast Cancer: A Systematic Review of Literature. AB - CONTEXT: Known polymorphisms of DNA repair genes can be associated with the risk of many types of cancer. There is no consensus regarding association between XRCC1 and OGG1 with breast cancer (BC). OBJECTIVES: The aim of this study is to collect relevant published studies systematically. DATA SOURCES: Sixty-two publications were identified through searching PubMed, PubMed Central, ISI web of knowledge, and reference list of related articles. STUDY SELECTION: We performed a systematic review according MOOSE guideline criteria. All longitudinal cohort and case-control studies investigating association of any type and grade of breast cancer with XRCC1 and OGG1 gene and their polymorphisms were eligible for initial inclusion. DATA EXTRACTION: Two authors screened titles and abstracts and extracted all needed information from eligible studies. Four research methodological components causing bias for the association between gene polymorphisms and breast cancer risk, including source of controls sampling, population ethnicity, sample size of studies and menopausal status of cases and controls was used for assessment of quality of studies. RESULTS: A total of 14,793 breast cancer cases and 15,409 controls were included in assessment of XRCC1 Arg194Trp. Four studies showed significant association and one study showed protective effect of XRCC1 Arg194Trp and BC. A total of 7,716 cases and 7,370 controls were included for XRCC1 Arg280His. Only one study showed significant association of XRCC1 Arg280His and breast cancer (OR = 1.82 (1.06 - 3.15). A total of 27,167 cases and 31,998 controls were included to estimate association between XRCC1 Arg399Gln polymorphism and breast cancer. Seven studies showed significant association and one showed protective effect of XRCC1 Arg399Gln and BC. A total of 9,417 cases and 11,087 controls were included for OGG1 Ser326Cys. Among studies focused on OGG1 Ser326Cys, none showed significant association with breast cancer. CONCLUSIONS: Systematic search of major databases identify many studies addressing the relationship between BC and susceptible alleles in the base excision repair genes and the fact that there are many variations in the magnitude of association depending on inheritance model and the population of the study. PMID- 27366309 TI - Molecular Detection and Typing of Human Papillomaviruses in Paraffin-Embedded Cervical Cancer and Pre-Cancer Tissue Specimens. AB - BACKGROUND: Cervical cancer is one of the important reasons of mortality among females. Prevention, early diagnosis and immediate treatment can affect the rate of mortality in this cancer and several epidemiological studies have shown a strong relationship between human papilloma viruses (HPVs) and cervical cancer. OBJECTIVES: The present study was conducted to survey HPV infections in a women population with cervical cancer and cervical dysplasia/metaplasia in southwest of Iran. MATERIALS AND METHODS: 72 paraffin-embedded cervical biopsies which had been previously archived from women with cervical cancer and cervical dysplasia were examined by polymerase chain reaction (PCR). Afterward, the detected HPV strains were typed by restriction fragment length polymorphism (RFLP) analysis of PCR amplicons. RESULTS: 60 out of 72 samples had necessary requirements and HPV DNA was detected in 43.3% of these samples. Most HPV positive samples belonged to women aged from 48 to 63 years. On the other hand, HPV infection among patients with squamous cell carcinoma (SCC) was 48.78% and in women with dysplasia/metaplasia was 26.66%. The most prevalent type of the human papilloma virus was HPV16 (100%). CONCLUSIONS: Knowing the most prevalent type of the human papilloma viruses circulating in the population (HPV16) can be applied in the future screening and managing programs of this major disease and also in vaccination against the prevalent types of the virus. Meanwhile, it seems that more studies should be performed to determine the role of different risk factors involved in development of the disease, especially those related with social behaviors and traditions with respect to different areas. PMID- 27366310 TI - Barriers for Early Detection of Cancer Amongst Urban Indian Women: A Cross Sectional Study. AB - BACKGROUND: Cancer is a leading cause of death globally. Every year, millions of cancer patients could be saved from premature death and and suffering if they had timely access to early detection and treatment. There are two main components of early detection: early diagnosis and screening. In India, cancers of cervix, breast, mouth/oropharynx are the most frequent cancers in women. These cancers are amenable to early detection. More than two third of the cancer patients are already in an advanced and incurable stage at the time of diagnosis. OBJECTIVES: This study was designed with the aim to know the reasons for non availment of cancer screening procedures and early diagnostic facilities. MATERIALS AND METHODS: This cross-sectional study was planned in Sangli, Miraj and Kupwad Corporation area during October 2013 - March 2014 by a pretested questionnaire. Women of 25 years and above were study subjects selected randomly from a cluster sample of ward with estimated sample size of 559 women. Statistical analysis was done with the help of IBM SPSS 22. RESULTS: Nearly 74% of women said that cancer is curable. For awareness about signs and symptoms, risk factors and screening test 82.3% women scored less than 50% of total score. Only 17.7% women had awareness score more than 50%. But their attitude score was > 50% in 85.2% of women. For practice score, 24.4% women scored > 50%. Significant association was found between awareness, attitude and practice scores and education, occupation and history of cancer in family, friends and neighborhood of respondents. CONCLUSIONS: Low awareness is the main barrier for undergoing cancer screening and early detection. There is a need of effective health education programme. PMID- 27366311 TI - Autophagy Gene Activity May Act As a Key Factor for Sensitivity of Tumor Cells to Oncolytic Vesicular Stomatitis Virus. AB - BACKGROUND: Beclin1 is an important, primary molecule for autophagy. OBJECTIVES: It is suggested that the control of the autophagy path increases the sensitivity of tumor cells to VSV. MATERIALS AND METHODS: In this study, the degree of Beclin1 gene expression in two cell lines, HeLa and A549, has been examined and the percentage of living cells subsequent infection with virus has been evaluated by MTT assay method. RESULTS: The results showed that the degree of Beclin1 gene expression in HeLa cells in comparison with A549 cells has reduced, and the sensitivity of these cells to vesicular stomatits virus (VSV) oncolysis is more than A549. CONCLUSIONS: It seems that by using some methods for reducing autophagy, it is possible to make tumor cells more sensitive to virotherapy and even other treatments. PMID- 27366313 TI - Evaluating the Prevalence of the Epidermal Growth Factor Receptor in Transitional Cell Carcinoma of Bladder and its Relationship With Other Prognostic Factors. AB - BACKGROUND: The most common malignancy in the urinary system has been bladder cancer and the most predominant histologic subtype has been transitional cell carcinoma (TCC). There were many molecular risk factors, related with poor prognosis. One of these factors was expression of epidermal growth factor receptor (EGFR). OBJECTIVES: The aim of this study was to evaluate the prevalence of the epidermal growth factor receptor in transitional cell carcinoma of bladder and its relationship with other prognostic factors. PATIENTS AND METHODS: This analytic descriptive study has performed with 61 patients with TCC of bladder after radical cystectomy whom have been hospitalized in Labbafinejad hospital in Tehran, Iran between 2007 and 2010. We have used Chi-square and t-test to analyze our data samples. RESULTS: Records of 61 patients have studied. Fifty three of the total samples were positive for EGFR expression (86.9%). Fifty samples of these fifty-three belonged to men and three others were women's samples (P = 0.46). Among the group with EGFR expression the results were as follows: 25 patients (47.2%) were 60 years old or less and 28 patients (52.8%) were older than 60 (P = 0.023), 16 patients (30.2%) had invasion to lamina properia, and the rest of them had invasion to deeper layers (P = 0.56). For most patients we could not determine the invasion of tumoral cells into the lymph nodes (Nx) (P = 0.067). Thirty four patients (64.2%) had not lymphovascular invasion (P = 0.44) and in forty three of patients (81.1%), perineural invasion have not seen (P = 0.23). Finally, 36 patients (67.9%) were grade 3 (P = 0.27). CONCLUSIONS: In this study we have concluded that most patients had EGFR positive expression. Also, except for the age, there was not any significant relation between expression of EGFR and the other prognostic factors such as, gender, invasion of the tumor into the layers, involving the lymph nodes, lymphovascular or perineural invasion, and grading. PMID- 27366312 TI - New Developments in Chronic Myeloid Leukemia: Implications for Therapy. AB - CONTEXT: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by overproduction of immature and matured myeloid cells in the peripheral blood, bone marrow and spleen. EVIDENCE ACQUISITION: A hallmark of CML is the presence of (9; 22) (q34; q11) reciprocal translocation, which is cytogenetically visible as Philadelphia chromosome (Ph) and results in the formation of BCR-ABL1 fusion protein. This fusion protein is a constitutively active tyrosine kinase which is necessary and sufficient for malignant transformation. The introduction of imatinib, a BCR-ABL1- targeting tyrosine kinase inhibitor (TKI) has revolutionized CML therapy. Subsequently, two other TKIs with increased activity against BCR-ABL1, dasatinib and nilotinib, were developed and approved for CML patients. Nevertheless, CML therapy faces major challenges. RESULTS: The first is the development of resistance to BCR-ABL1 inhibitors in some patients, which can be due to BCR-ABL1 overexpression, differences in cellular drug influx and efflux, activation of alternative signaling pathways, or emergence of BCR-ABL1 kinase domain mutations during TKI treatment. The second is the limited efficiency of BCR-ABL1-TKIs in blast crisis (BC) CML. The third is the insensitivity of CML stem cells to BCR-ABL1 inhibitors. Conventional chemotherapeutics and BCR-ABL1 inhibitors which act by inhibiting cell proliferation and inducing apoptosis, are ineffective against quiescent CML stem cells. CONCLUSIONS: A better understanding of the mechanisms that underlie TKI resistance, progression to BC, genomic instability and stem cell quiescence is essential to develop curative strategies for patients with CML. PMID- 27366314 TI - Effects of Two Common Promoter Polymorphisms of Transforming Growth Factor-beta1 on Breast Cancer Risks in Ahvaz, West South of Iran. AB - BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) has a critical role in breast cancer initiation and progression. OBJECTIVES: We have investigated the possible differences in two promoter polymorphisms (-509C/T and -800G/A) of TGF beta1 gene between breast cancer cases and controls. PATIENTS AND METHODS: A total of 100 patients with confirmed breast cancer and 100 subjects without breast cancer was selected. Two promoter polymorphisms (-509C/T and -800G/A) of TGF-beta1 gene were genotyped using PCR-based restriction fragment length polymorphism (RFLP) method. RESULTS: The allele frequencies were 63% for C allele and 37% for T allele of SNP -509C/T and 66% for G allele and 34% for A allele of SNP -800G/A. Although no significant difference has observed between two groups, according to the genotype distribution, However, the TT genotype of -509 and AA genotype of -800 was significantly associated with breast cancer risk [odds ratio (OR) = 2.409; 95% confidence interval (CI) = 1.087 - 5.337, P = 0.030; and OR = 2.383; CI = 1.039 - 5.40, P = 0.040, respectively]. In addition, a multinomial logistic regression model shown, homozygous of -800 G/A (OR = 0.570; 95% CI = 0.362 - 0.896, P = 0.015); and HDL-C (OR = 0.935; 95% CI = 0.906 - 0.965, P < 0.001) were the selected variables associated with the presence of breast cancer. Haplotype analysis has shown no significant association between TGF-beta1 haplotypes and breast cancer risk. CONCLUSIONS: Our results indicated that among two promoter polymorphisms of the TGF-beta1gene, -800G/A compared to -509C/T is more associated with breast cancer. PMID- 27366315 TI - Cost-Effectiveness of Three Rounds of Mammography Breast Cancer Screening in Iranian Women. AB - BACKGROUND: Breast cancer is the most common cancer in Iranian women as is worldwide. Mammography screening has been introduced as a beneficial method for reducing mortality and morbidity of this disease. OBJECTIVES: We developed an analytical model to assess the cost effectiveness of an organized mammography screening program in Iran for early detection of the breast cancer. PATIENTS AND METHODS: This study is an economic evaluation of mammography screening program among Iranian woman aged 40 - 70 years. A decision tree and Markov model were applied to estimate total quality adjusted life years (QALY) and lifetime costs. RESULTS: The results revealed that the incremental cost effectiveness ratio (ICER) of mammography screening in Iranian women in the first round was Int. $ 37,350 per QALY gained. The model showed that the ICER in the second and third rounds of screening program were Int. $ 141,641 and Int. $ 389,148 respectively. CONCLUSIONS: Study results identified that mammography screening program was cost effective in 53% of the cases, but incremental cost per QALY in the second and third rounds of screening are much higher than the accepted payment threshold of Iranian health system. Thus, evaluation of other screening strategies would be useful to identify more cost-effective program. Future studies with new national data can improve the accuracy of our finding and provide better information for health policy makers for decision making. PMID- 27366316 TI - Health Manpower Development (HMD) Corner Stone of Improving National Health System. PMID- 27366317 TI - The new chiropractic. AB - BACKGROUND: Physical manipulation and manual therapies are thousands of years old. The most popular western world iteration of these therapies is delivered by chiropractors. It can be argued that the collective public health benefit from chiropractic for spinal pain has been very substantial, however as chiropractic has transitioned from craft to profession it has encountered many internally and externally driven machinations that have retarded its progress to a fully accepted allied health profession. This article sets out a ten point plan for a new chiropractic that will achieve full acceptance for this troubled profession. DISCUSSION: This article is based on a keynote speech known as the FG Roberts Memorial Address delivered on October 10, 2015, in Melbourne, Australia at the Chiropractic & Osteopathic College of Australasia and Chiropractic Australia national conference. The ten point plan consists of the following: improving the pre-professional education of chiropractors, establishing a progressive identity, developing a special interest for the profession, marginalising the nonsensical elements of the profession, being pro-public health, supporting the legitimate organised elements of the profession, improving clinical practice, embracing evidence based practice, supporting research and showing personal leadership. CONCLUSION: Adherence to this fresh ten point plan will, over time, see the chiropractic profession gain full legitimacy in the allied health field and acceptance by other health providers, policy makers and the public at large. PMID- 27366318 TI - Bringing experiential learning into the lecture theatre using 3D printed objects. AB - The ability to conceptualize 3D shapes is central to understanding biological processes. The concept that the structure of a biological molecule leads to function is a core principle of the biochemical field. Conceptual teaching usually involves vocal explanations or using two dimensional slides or video presentations. A deeper understanding may be obtained by the handling of objects. 3D printed biological molecules can be used as active learning tools to stimulate engagement in large group lectures. These models can be used to build upon initial core knowledge which can be delivered in either a flipped form or a more didatic manner. Within the teaching session the students are able to learn by handling, rotating and viewing the objects to gain an appreciation of an enzyme's active site or the structure of DNA for example. Models and other artefacts are handled in small groups and act as a focus for talking points to generate conversation. Through this approach core knowledge is first established and then supplemented with high level problem solving through a "Think-Pair-Share" cooperative learning strategy. The teaching delivery is adjusted based around experiential learning activities by moving the object from mental cognition and into a physical environment leading to student engagement in the lecture theatre and a dialog with the lecturer. The use of artefacts in teaching allows the lecturer to create interactive sessions that challenge and enable the student. This approach can be applied at all levels and across many disciplines. PMID- 27366319 TI - Tripartite genome of all species. AB - Neutral theory has dominated the molecular evolution field for more than half a century, but it has been severely challenged by the recently emerged Maximum Genetic Diversity (MGD) theory. However, based on our recent work of tripartite human genome architecture, we found that MGD theory may have overlooked the regulatory but variable genomic regions that increase with species complexity. Here we propose a new molecular evolution theory named Increasing Functional Variation (IFV) hypothesis. According to the IFV hypothesis, the genome of all species is divided into three regions that are 'functional and invariable', 'functional and variable' and 'non-functional and variable'. While the 'non functional and variable' region decreases as species become more complex, the other two regions increase. PMID- 27366320 TI - Digital methodology to implement the ECOUTER engagement process. AB - ECOUTER (Employing COnceptUal schema for policy and Translation Engagement in Research) - French for 'to listen' - is a new stakeholder engagement method incorporating existing evidence to help participants draw upon their own knowledge of cognate issues and interact on a topic of shared concern. The results of an ECOUTER can form the basis of recommendations for research, governance, practice and/or policy. This paper describes the development of a digital methodology for the ECOUTER engagement process based on currently available mind mapping freeware software. The implementation of an ECOUTER process tailored to applications within health studies are outlined for both online and face-to-face scenarios. Limitations of the present digital methodology are discussed, highlighting the requirement of a purpose built software for ECOUTER research purposes. PMID- 27366322 TI - Coronary artery bypass grafting in South Asian patients: Impact of gender. AB - BACKGROUND: Outcomes following Coronary artery bypass grafting (GABG) vary between genders, with females having a higher postoperative mortality than males. Most of the studies are on Caucasian or mixed population and it is postulated that Asian population and in particular women have higher morbidity and mortality. In this study we have compared outcomes of elective CABG in men and women of South Asian origin in terms of morbidity and mortality. METHODS: From January 2006 to December 2012, 1970 patients underwent isolated elective CABG at the Aga Khan University Hospital, Pakistan were selected. The prospectively collected data was analyzed retrospectively including univariate and multivariate analysis to find the association of morbidity and mortality. RESULTS: Among the study patients 1664 (85%) were male and 306 (15%) female. Hypertension and diabetes were the most common comorbid conditions seen preoperatively in female patients. Atrial fibrillation and sepsis were the most common postop complications seen in females. In hospital mortality was 3.9% in female underwent CABG as against 0.6% in male. Multivariate analysis showed older age, renal failure, dyslipidemia and prolonged cross clamp time as predictors of postoperative morbidity. Multivariate analysis showed female gender, age and renal failure as predictors of in hospital mortality. CONCLUSIONS: Female gender is an independent risk factor for postoperative mortality following CABG however, female gender is not found to be independent risk factor for morbidity. The trend of higher mortality in female patients was comparable to most studies done on Caucasian patients. PMID- 27366321 TI - The recommendations of Chinese Parkinson's disease and movement disorder society consensus on therapeutic management of Parkinson's disease. AB - BACKGROUND: Parkinson's disease (PD) is a chronic, progressive and debilitating disease, which affects over 2.5 million people in China. PD is characterized clinically by resting tremor, muscular rigidity, bradykinesia and postural instability. As the disease progresses, additional complications can arise such as non-motor and neurobehavioral symptoms. Pharmacological treatment and surgical intervention for PD have been implemented in China. Until 10 years ago, there was lack of standardization for the management of PD in different regions and among different physicians, leading to different treatment levels in different regions and different physicians. Since then, the Chinese Parkinson's Disease and Movement Disorder Society have published three versions of guidelines for the management of PD in China, in 2006, 2009 and 2014, respectively. Correspondingly, the overall level of treatment for PD in China improved. OBJECTIVES: To update the treatment guidelines based on current foreign and domestic practice guidelines and clinical evidence, and to improve the treatment options available to physicians in the management of PD. SUMMARY: A variety of treatment recommendations in the treatment guidelines have been proposed, including physical activity and disease-modifying medication, which should be initiated at the early-stage of the disease. The principles of dosage titration should be followed to avoid acute adverse reactions to the drugs, to achieve a satisfactory clinical effect with a low dose and to reduce the incidence of long-term motor complications. Moreover, different treatment strategies should be considered at different stages of the disease. Importantly, treatment guidelines and personalized treatments should be valued equally. A set of treatment recommendations has been developed to assist physicians to improve and optimize clinical outcomes for patients with PD in China. PMID- 27366323 TI - Decreases in cerebral saturation in patients with septic shock are associated with increased risk of death: a prospective observational single center study. AB - BACKGROUND: The mortality rate from septic shock has been declining. Cerebral hypoxia, measured non-invasively with cerebral oximetry, has been correlated with neurologic and non-neurologic sequelae. Whether cerebral desaturations occur in septic shock patients and what consequences these may have is untested. METHODS: Adult patients with septic shock had cerebral saturation monitoring initiated. The primary objective was to determine if the incidence and magnitude of cerebral desaturations in septic shock patients correlated with delirium. We also compared the incidence and magnitude of cerebral desaturations in patients with septic shock with patients undergoing high-risk non-cardiac surgical procedures, a group known to be at high risk for cerebral desaturations. RESULTS: Fifteen patients were enrolled. Twelve (80 %) patients had a decrease in SctO2 below 65 %. Delirium was not associated with the area under the curve of an SctO2 of 65 % (p = 0.84). Patients who died of septic shock had more significant decreases in SctO2 than those who survived (p = 0.04). Decreased SctO2 was more common in patients with septic shock and was of greater magnitude than those undergoing high-risk non-cardiac surgery. CONCLUSIONS: Cerebral desaturations occur more commonly and are of a greater magnitude in septic shock patients compared with those undergoing high-risk non-cardiac surgery. There did not appear to be a relationship between the incidence or magnitude of decreases in SctO2 and ICU delirium. Patients who died of septic shock had more significant decreases in SctO2 than patients who survived. PMID- 27366324 TI - A comparison of prognostic significance of strong ion gap (SIG) with other acid base markers in the critically ill: a cohort study. AB - BACKGROUND: This cohort study compared the prognostic significance of strong ion gap (SIG) with other acid-base markers in the critically ill. METHODS: The relationships between SIG, lactate, anion gap (AG), anion gap albumin-corrected (AG-corrected), base excess or strong ion difference-effective (SIDe), all obtained within the first hour of intensive care unit (ICU) admission, and the hospital mortality of 6878 patients were analysed. The prognostic significance of each acid-base marker, both alone and in combination with the Admission Mortality Prediction Model (MPM0 III) predicted mortality, were assessed by the area under the receiver operating characteristic curve (AUROC). RESULTS: Of the 6878 patients included in the study, 924 patients (13.4 %) died after ICU admission. Except for plasma chloride concentrations, all acid-base markers were significantly different between the survivors and non-survivors. SIG (with lactate: AUROC 0.631, confidence interval [CI] 0.611-0.652; without lactate: AUROC 0.521, 95 % CI 0.500-0.542) only had a modest ability to predict hospital mortality, and this was no better than using lactate concentration alone (AUROC 0.701, 95 % 0.682-0.721). Adding AG-corrected or SIG to a combination of lactate and MPM0 III predicted risks also did not substantially improve the latter's ability to differentiate between survivors and non-survivors. Arterial lactate concentrations explained about 11 % of the variability in the observed mortality, and it was more important than SIG (0.6 %) and SIDe (0.9 %) in predicting hospital mortality after adjusting for MPM0 III predicted risks. Lactate remained as the strongest predictor for mortality in a sensitivity multivariate analysis, allowing for non-linearity of all acid-base markers. CONCLUSIONS: The prognostic significance of SIG was modest and inferior to arterial lactate concentration for the critically ill. Lactate concentration should always be considered regardless whether physiological, base excess or physical-chemical approach is used to interpret acid-base disturbances in critically ill patients. PMID- 27366325 TI - 'Clostridium massiliodielmoense', a new species isolated from the human gut microbiota. AB - Herein, we report the main characteristics of 'Clostridium massiliodielmoense' strain mt26 (= CSUR P2255), representative of a new species isolated from the gastrointestinal tract of a healthy 28-month-old Senegalese boy. PMID- 27366326 TI - Relative quantification of phosphoproteomic changes in grapevine (Vitis vinifera L.) leaves in response to abscisic acid. AB - In a previous transcriptomic analysis, abscisic acid (ABA) was found to affect the abundance of a number of transcripts in leaves of Cabernet Sauvignon grapevines with roots that had been exposed to 10 MUm ABA for 2 h. Other work has indicated that ABA affects protein abundance and protein phosphorylation as well. In this study we investigated changes in protein abundance and phosphorylation of Cabernet Sauvignon grapevine leaves. Protein abundance was assessed by both label free and isobaric-label quantitive proteomic methods. Each identified common proteins, but also additional proteins not found with the other method. Overall, several thousand proteins were identified and several hundred were quantified. In addition, hundreds of phosphoproteins were identified. Tens of proteins were found to be affected in the leaf after the roots had been exposed to ABA for 2 h, more than half of them were phosphorylated proteins. Many phosphosites were confirmed and several new ones were identified. ABA increased the abundance of some proteins, but the majority of the proteins had their protein abundance decreased. Many of these proteins were involved in growth and plant organ development, including proteins involved in protein synthesis, photosynthesis, sugar and amino-acid metabolism. This study provides new insights into how ABA regulates plant responses and acclimation to water deficits. PMID- 27366327 TI - Noninvasive Surface Imaging of Breast Cancer in Humans using a Hand-held Optical Imager. AB - X-ray mammography, the current gold standard for breast cancer detection, has a 20% false-negative rate (cancer is undetected) and increases in younger women with denser breast tissue. Diffuse optical imaging (DOI) is a safe (nonionizing), and relatively inexpensive method for noninvasive imaging of breast cancer in human subjects (including dense breast tissues) by providing physiological information (e.g. oxy- and deoxy- hemoglobin concentration). At the Optical Imaging Laboratory, a hand-held optical imager has been developed which employs a breast contourable probe head to perform simultaneous illumination and detection of large surfaces towards near real-time imaging of human breast cancer. Gen-1 and gen-2 versions of the handheld optical imager have been developed and previously demonstrated imaging in tissue phantoms and healthy human subjects. Herein, the hand-held optical imagers are applied towards in vivo imaging of breast cancer subjects in an attempt to determine the ability of the imager to detect breast tumors. Five female human subjects (ages 51-74) diagnosed with breast cancer were imaged with the gen-1 optical imager prior to surgical intervention. One of the subjects was also imaged with the gen-2 optical imager. Both imagers use 785 nm laser diode sources and ICCD camera detectors to generate 2D surfaces maps of total hemoglobin absorption. The subjects lay in supine position and images were collected at various locations on both the ipsilateral (tumor-containing) and contralateral (non-tumor containing) breasts. The optical images (2D surface maps of optical absorption due to total hemoglobin concentration) show regions of higher intensity at the tumor location, which is indicative of increased vasculature and higher blood content due to the presence of the tumor. Additionally, a preliminary result indicates the potential to image lymphatic spread. This study demonstrates the potential of the hand-held optical devices to noninvasively image breast cancer in human subjects. PMID- 27366329 TI - Fascicular Visual Field Defects in Open-Angle Glaucoma: Evaluation with Microperimetry. AB - Purpose. Use of microperimetry (Mp-1), correlating with Humphrey perimetry (30-2 program), in patients affected by primary open-angle glaucoma (POAG) with perimetric defects, in order to obtain an evaluation of the accuracy of the results obtained by Mp-1. Materials and Methods. In this study 40 eyes of 25 patients affected by POAG with perimetric defects were included. All patients underwent microperimetry test by Nidek Mp-1 (NAVIS software version 1.7.2, Nidek Technologies). Mean sensitivity values expressed in decibel (dB) of all tested dots and mean values for each quadrant obtained by microperimetric test were correlated with corresponding quadrants obtained by static perimetry analysis. Data were analyzed by Pearson's correlation and Bland-Altman analysis. Results. Interpolated data showed that mean sensitivity values in all spots tested by Mp-1 (11.98 dB, SD 4.31) may be significantly correlated with mean total values obtained by Humphrey 30-2 perimetry (17.95, SD 4.32), with correlation coefficient of 0.556. Conclusions. Topographic visualization of the perimetric alteration by microperimetry allows retesting areas with reduced sensitivity which are topographically visualized and displayable on the ocular fundus examination, avoiding worsening of the functional defect by better modulation of the antiglaucoma therapy and therefore it allows better monitoring of the pathologic functional damage. PMID- 27366328 TI - Is Floppy Eyelid Syndrome More Prevalent in Obstructive Sleep Apnea Syndrome Patients? AB - Controversial findings are reported about the relationship between floppy eyelid syndrome (FES) and obstructive sleep apnea syndrome (OSAS). The main goal of this study was to evaluate whether FES is more prevalent in OSAS patients by performing a meta-analysis. A comprehensive literature search of Pubmed, Embase, and Cochrane databases was performed. Only studies related to the prevalence of FES in OSAS were included in the meta-analysis. We estimated a pooled odds ratio (OR) for the prevalence of FES in OSAS. In total, 6 studies with 767 participants met the inclusion criteria. Using a fixed-effects model, the pooled OR was 4.12. The test for the overall effect revealed that FES was statistically prevalent in OSAS patients when compared with that in non-OSAS subjects (Z = 4.98, p < 0.00001). In the subgroup analysis by OSAS severity, the incidence of FES in OSAS increased with severity of OSAS as indicated with increased OR values (OR = 2.56, 4.62, and 7.64 for mild, moderate, and severe OSAS). In conclusion, the results indicate that FES is more prevalent in OSAS patients. However, this result was based only on unadjusted estimates. Prospective cohort studies are needed to determine whether OSAS is an independent risk factor for FES. PMID- 27366330 TI - Recruiting and Engaging Older Men in Evidence-Based Health Promotion Programs: Perspectives on Barriers and Strategies. AB - Evidence-based health promotion programs are effective at reducing health risks and healthcare costs among older adults, but few men participate in the programs. This mixed methods study aimed to gain insight into the barriers to recruiting and engaging older men in evidence-based health promotion programs offered by the Healthy Aging Regional Collaborative of South Florida (HARC). Fourteen program coordinators participated in a focus group to identify barriers and strategies to improve male participation, and 49 instructors participated in a survey to triangulate the findings. Themes among barriers to male participation included women outnumbering men in the implementation sites and programs, conflict between male gender roles and the programs, and preference for other activities. Themes among strategies included public support of programs by male community leaders, program advertisements featuring males, and adapting program content. Survey results supported themes identified in the focus group. Nearly 78% of the survey respondents agreed that the perception of exercise programs as feminine was a barrier and over 90% of the survey respondents believed program advertisements featuring men would increase male participation. Findings indicate that health promotion programs and recruiting strategies need to be tailored to the unique needs and preferences of older men to improve participation. PMID- 27366331 TI - PCR-Based Molecular Diagnosis of Hepatitis Virus (HBV and HDV) in HCV Infected Patients and Their Biochemical Study. AB - Seroprevalence of HCV indicates that HCV is found in more than 10% of HBV- or HDV infected patients worldwide leading to liver disease. Here we show HBV and HDV coinfection association with HCV infected Pakistani patients, study of disease severity, and possible interpretation of associated risk factors in coinfected patients. A total of 730 liver diseased patients were included, out of which 501 were found positive for HCV infection via PCR. 5.1% of patients were coinfected with HBV while 1% were coinfected with HBV and HDV both. LFTs were significantly altered in dually and triply infected patients as compared to single HCV infection. Mean bilirubin, AST, and ALT levels were highest (3.25 mg/dL, 174 IU/L, and 348 IU/L) in patients with triple infection while dual infection LFTs (1.6 mg/dL, 61 IU/L, and 74 IU/L) were not high as in single infection (1.9 mg/dL, 76 IU/L, and 91 IU/L). The most prominent risk factor in case of single (22%) and dual infection (27%) group was "reuse of syringes" while in triple infection it was "intravenous drug users" (60%). It is concluded that HBV and HDV coinfections are strongly associated with HCV infected Pakistani patients and in case of severe liver disease the possibility of double and triple coinfection should be kept in consideration. PMID- 27366332 TI - Accidental Entrapment of Electrical Mapping Catheter by Chiari's Network in Right Atrium during Catheter Ablation Procedure. AB - A 78-year-old male was admitted to our hospital due to frequent palpitation. His electrocardiogram (ECG) presented regular narrow QRS tachycardia with 170 bpm, and catheter ablation was planned. During electroanatomical mapping of the right atrium (RA) with a multiloop mapping catheter, the catheter head was entrapped nearby the ostium of inferior vena cava. Rotation and traction of the catheter failed to detach the catheter head from the RA wall. Exfoliation of connective tissue twined around catheter tip by forceps, which were designed for endomyocardial biopsy, succeeded to retract and remove the catheter. Postprocedural echocardiography and pathologic examination proved the existence of Chiari's network. The handling of complex catheters in the RA has a potential risk of entrapment with Chiari's network. PMID- 27366333 TI - A Case of Glucocorticoid Remediable Aldosteronism and Thoracoabdominal Aneurysms. AB - Glucocorticoid remediable aldosteronism (GRA) is rare familial form of primary aldosteronism characterized by a normalization of hypertension with the administration of glucocorticoids. We present a case of GRA and thoracoabdominal aneurysm complicated by multiple aortic dissections requiring complex surgical and endovascular repairs. Registry studies have shown a high rate of intracranial aneurysms in GRA patients with high case fatality rates. The association of thoracoabdominal aneurysms with GRA has not been described, thus far, in literature. Studies have shown that high tissue aldosterone levels concomitant with salt intake have a significant role in the pathogenesis of aneurysms and this may explain the formation of aneurysms in the intracranial vasculature and aorta. The association of GRA with thoracic aortic aneurysms needs to be further studied to develop screening recommendations for early identification and optimal treatment. Also, the early use of mineralocorticoid antagonists may have a significant preventive and attenuating effect in aneurysm formation, an association which needs to be confirmed in future studies. PMID- 27366334 TI - Esophageal Microperforation due to Calcified Mediastinal Lymph Node Leading to Tracheoesophageal Fistula. AB - A 42-year-old male presented with worsening gastroesophageal reflux disease symptoms and cough. The clinical symptoms during the early course of illness were striking for aspiration pneumonia. He was given a prescription of proton pump inhibitors and antibiotics. Rapid decline in the clinical condition with worsening respiratory status was noted. Worsening symptoms of fever, cough, and chest pain prompted further diagnostic work-up suggesting esophageal microperforation. Esophagogram was found to be suggestive of tracheoesophageal fistula. The tracheoesophageal fistula was due to subcarinal lymph node of nontuberculous origin. PMID- 27366335 TI - Thrombocytopenia and Postpartum Hemorrhage in a Woman with Chromosome 22q11.2 Deletion Syndrome. AB - Chromosome 22q11.2 deletion syndrome, also known as DiGeorge or velocardiofacial syndrome, is associated with a wide spectrum of phenotypic features. It is known to be associated with severe macrothrombocytopenia. Postpartum hemorrhage is a leading cause of maternal morbidity and mortality globally. Chromosome 22q11.2 deletion syndrome is rare cause of thrombocytopenia that can be a significant risk factor for life-threatening postpartum hemorrhage. We report a case of postpartum hemorrhage in a woman with 22q11.2 deletion syndrome causing severe macrothrombocytopenia. PMID- 27366336 TI - Dicephalus Parapagus Conjoined Twins Diagnosed by First-Trimester Ultrasound. AB - Conjoined twins are a rare phenomenon, occurring in 1% of monochorionic twin gestation, with an incidence of 1 : 50 000 to 1 : 100 000. Many conjoined twins have abnormalities incompatible with life, so early prenatal diagnosis is very important for optimal management of both pregnancy and delivery. We report a case of dicephalus parapagus conjoined twins, sharing a single heart, diagnosed at 12 weeks' gestation. With early ultrasound diagnosis, we were able to provide appropriate and timely prenatal counseling to the family. PMID- 27366337 TI - Occult Cranial Cervical Dislocation: A Case Report and Brief Literature Review. AB - Study Design. Retrospective case report and review. Objective. Cranial cervical dislocation (CCD) is commonly a devastating injury. Delay in diagnosis has been found to lead to worse outcomes. Our purpose is to describe a rare case of occult cranial cervical dislocation (CCD) and use it to highlight key clinical and radiographic findings to ensure expedited diagnosis and proper management avoiding delays and subsequent neurologic deterioration. Method. Case report with literature review. Results. We describe a unique case of occult cranial cervical dislocation where initial imaging of the cervical spine failed to illustrate displacement of the occipital-cervical (O-C1) articulation or C1-C2 articulation. Careful evaluation of subtle radiographic clues suggested a more severe injury than initial review. Additional imaging was obtained due to these subtle clues confirming true cranial cervical dislocation allowing subsequent treatment with no neurologic sequelae. Conclusion. A high index of suspicion of CCD may prevent injury in select patients who present without gross cord compromise. Careful consideration of associated fractures, soft tissue injuries, and mechanism of injury are essential clues to the correct diagnosis and management of injuries to the craniocervical junction (CCJ). PMID- 27366338 TI - Anatomic Locking Plate Fixation for Scaphoid Nonunion. AB - Nonunion can occur relatively frequently after scaphoid fracture and appears to be associated with severity of injury. There have been a number of techniques described for bone grafting with or without screw fixation to facilitate fracture healing. However, even with operative fixation of scaphoid fractures with bone grafting nonunion or malunion rates of 5 to 10 percent are still reported. This is the first report of an anatomic locking plate for scaphoid fracture repair in a 25-year-old right hand dominant healthy male. PMID- 27366339 TI - HIV Infection and Osteoarticular Tuberculosis: Strange Bedfellows. AB - We report the case of a 47-year-old female patient with rheumatoid arthritis and HIV infection presenting with a 3-week history of a painful swollen knee, increased serum inflammatory markers, and a low CD4 lymphocyte count. The diagnosis of TB arthritis was made by synovial fluid culture, GeneXpert/PCR, and confirmed by histopathology of a synovial biopsy. A mini literature review suggests that although HIV infection is associated with extrapulmonary TB, osteoarticular TB is a relatively unusual presentation in an HIV positive patient. The diagnostic utility of the GeneXpert test is explored. We also describe the patient's good response to an intra-articular corticosteroid injection in combination with standard anti-TB therapy. PMID- 27366340 TI - Undiagnosed Sjogren's Syndrome Presenting as Mesenteric Panniculitis. AB - Mesenteric panniculitis is a rare inflammatory and fibrotic process that affects the small intestine mesentery. It may occur following abdominal surgery or in association with a variety of conditions, including malignancy, infection, and certain autoimmune and inflammatory conditions. Herein, an unusual case of mesenteric panniculitis in a patient with primary Sjogren's syndrome will be presented. The patient presented with abdominal pain, weight loss, sicca symptoms, fatigue, and arthralgia. An abdominal CT revealed mesenteric fat stranding and prominent lymph nodes of the small intestine mesentery. She was found on laboratory workup to have positive antinuclear and anti-SSa antibodies. Minor salivary gland lip biopsy revealed focal lymphocytic sialadenitis. The patient's symptoms and CT findings improved with corticosteroids. This case suggests that Sjogren's syndrome should be considered as an underlying disease process in the evaluation of patients with mesenteric panniculitis. PMID- 27366341 TI - Systemic Lupus Erythematosus Presenting with Massive Ascites: A Case of Pseudo Pseudo Meigs Syndrome. AB - The case presented is consistent with the phenomenon known as Pseudo-Pseudo Meigs Syndrome (PPMS). In it, we describe a young woman with newly diagnosed Systemic Lupus Erythematosus presenting with ascites, pleural effusions, and an elevated CA-125 level. Although rare, and of uncertain etiology, PPMS is becoming increasingly recognized in the literature. It should be considered as a differential diagnosis in such patients, along with the search for malignancy. PMID- 27366342 TI - Characteristics of Nonmotor Symptoms in Progressive Supranuclear Palsy. AB - Objectives. To explore the clinical correlates of nonmotor symptoms (NMS) in progressive supranuclear palsy (PSP) and their differences from healthy controls and patients with Parkinson's disease (PD). Methods. Twenty-seven PSP patients, 27 age- and gender-matched healthy controls (HC), and 27 age- and gender-matched PD patients were included for this case-control study. NMS were assessed using the Nonmotor Symptoms Scale (NMSS, including 9 domains). Results. All PSP patients reported NMS. The frequency and severity of "sleep/fatigue," "mood/apathy," "attention/memory," "gastrointestinal," "sexual dysfunction," and "miscellaneous" domains in PSP group were significantly higher than those in HC group (P < 0.05). The frequency of "mood/apathy," "attention/memory," and "sexual dysfunction" domains and the severity of "attention/memory" and "gastrointestinal" domains in PSP group were significantly higher than those in PD group (P < 0.05). The "attention/memory" domain in PSP had a significant but weak-to-moderate correlation with age (R = 0.387, P = 0.046) and onset age (R = 0.406, P = 0.036). Conclusions. NMS are common in PSP patients. Patients with PSP seem to be subjected to more frequent and severe specific NMS compared to healthy aging subjects and PD patients. Older PSP patients and late-onset patients are likely to be subjected to cognitive decline. PMID- 27366344 TI - Risk Factors Associated with the Occurrence of Gastrointestinal Helminths among Indigenous Donkeys (Equus asinus) in Northeastern Nigeria. AB - Aim. This survey study was conducted from April 2014 through March 2015 in Bauchi, Yobe, and Gombe states, northeastern Nigeria, to explore the risk factors associated with the occurrence of gastrointestinal helminthosis among indigenous donkeys (Equus asinus). Materials and Methods. A total of six hundred fresh faecal samples were randomly collected from indigenous donkeys of varying age, sex, and settlements. Simple flotation and sedimentation techniques were used for the detection of helminths eggs. Results. Three gastrointestinal nematode parasites were encountered including Strongyle, Parascaris equorum, and Oxyuris equi. An overall prevalence of 98.3% was obtained, of which 78.3%, 40.3%, and 17.5% were, respectively, from Strongyle, Parascaris equorum, and Oxyuris equi. Age, sex, and season were not statistically associated with the risk of helminth infection as were the different study areas (p > 0.05). However, body condition score, settlement, anthelminthic medication history, and management practices were significantly associated with the risk of gastrointestinal helminthosis. Statistically high prevalence of helminthic infections was observed in donkeys, with poor (thin) body condition, from rural settlements, that were not dewormed and raised under poor management systems (p < 0.001). Conclusion. It is concluded from the study that gastrointestinal helminths particularly Strongyle were endemic among the indigenous donkeys in northeastern Nigeria. Further control and preventive measures were discussed. PMID- 27366345 TI - In vitro antimicrobial activity of five essential oils on multidrug resistant Gram-negative clinical isolates. AB - AIM/BACKGROUND: The emergence of drug-resistant pathogens has drawn attention on medicinal plants for potential antimicrobial properties. The objective of the present study was the investigation of the antimicrobial activity of five plant essential oils on multidrug resistant Gram-negative bacteria. MATERIALS AND METHODS: Basil, chamomile blue, origanum, thyme, and tea tree oil were tested against clinical isolates of Acinetobacter baumannii (n = 6), Escherichia coli (n = 4), Klebsiella pneumoniae (n = 7), and Pseudomonas aeruginosa (n = 5) using the broth macrodilution method. RESULTS: The tested essential oils produced variable antibacterial effect, while Chamomile blue oil demonstrated no antibacterial activity. Origanum, Thyme, and Basil oils were ineffective on P. aeruginosa isolates. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration values ranged from 0.12% to 1.50% (v/v) for tea tree oil, 0.25-4% (v/v) for origanum and thyme oil, 0.50% to >4% for basil oil and >4% for chamomile blue oil. Compared to literature data on reference strains, the reported MIC values were different by 2SD, denoting less successful antimicrobial activity against multidrug resistant isolates. CONCLUSIONS: The antimicrobial activities of the essential oils are influenced by the strain origin (wild, reference, drug sensitive, or resistant) and it should be taken into consideration whenever investigating the plants' potential for developing new antimicrobials. PMID- 27366343 TI - Pathophysiology of Motor Dysfunction in Parkinson's Disease as the Rationale for Drug Treatment and Rehabilitation. AB - Cardinal motor features of Parkinson's disease (PD) include bradykinesia, rest tremor, and rigidity, which appear in the early stages of the disease and largely depend on dopaminergic nigrostriatal denervation. Intermediate and advanced PD stages are characterized by motor fluctuations and dyskinesia, which depend on complex mechanisms secondary to severe nigrostriatal loss and to the problems related to oral levodopa absorption, and motor and nonmotor symptoms and signs that are secondary to marked dopaminergic loss and multisystem neurodegeneration with damage to nondopaminergic pathways. Nondopaminergic dysfunction results in motor problems, including posture, balance and gait disturbances, and fatigue, and nonmotor problems, encompassing depression, apathy, cognitive impairment, sleep disturbances, pain, and autonomic dysfunction. There are a number of symptomatic drugs for PD motor signs, but the pharmacological resources for nonmotor signs and symptoms are limited, and rehabilitation may contribute to their treatment. The present review will focus on classical notions and recent insights into the neuropathology, neuropharmacology, and neurophysiology of motor dysfunction of PD. These pieces of information represent the basis for the pharmacological, neurosurgical, and rehabilitative approaches to PD. PMID- 27366346 TI - An in vitro evaluation of the Native American ethnomedicinal plant Eryngium yuccifolium as a treatment for snakebite envenomation. AB - AIM: At least seven North American tribes specifically mention the use of Eryngium (typically roots) as an anti-snake venom therapy. As snake envenomation is an endemic, life-threatening medical risk, is there a scientific basis for the Native American ethnomedicine? Could this be demonstrated in an assay amenable to mechanistic evaluation and high throughput screening for later isolation and possible evaluation as a source for a lead drug? MATERIALS AND METHODS: Proteases, mainly metalloproteases, are thought to be the main pathological agents in most American snake venoms. Water extracts of four plant parts of Eryngium yuccifolium were tested for enzyme inhibition in three highly sensitive in vitro protease assays, with multiple venoms. RESULTS: Interestingly, activity was found in all plant parts, not just the roots, in the general protease assay, also in the most specific assay for collagenases, but less so for elastases where enzymatic activity was low, and against five species of American snake venoms. Inhibition spared the activity of a mammalian elastase, suggesting it has some specificity. In dose response assays, inhibitory activity in extracts of Eryngium was noticeably more effective than randomly chosen plants and comparable to some others. CONCLUSIONS: All data shown here are consistent with pharmacological inhibition of proteases in at least selected venoms of common venomous snakes by Eryngium extracts. Moreover, as the genus is widely distributed in America, the ethnological practice of using this plant as an anti-snake venom treatment is supportable, may have been common, and suggests further bioactivity and phytochemical studies are warranted. PMID- 27366347 TI - Antimicrobial and cytotoxicity properties of the organic solvent fractions of Clerodendrum myricoides (Hochst.) R. Br. ex Vatke: Kenyan traditional medicinal plant. AB - BACKGROUND/AIM: Clerodendrum myricoides is a Kenyan herbal plant used in the management of respiratory diseases. In the current study, we investigated in vitro antimicrobial activity, cytotoxicity, and phytochemical screening of C. myricoides. MATERIALS AND METHODS: Antimicrobial activities of C. myricoides organic fractions against array of microorganisms including: (i) Mycobacterium tuberculosis (MTB) H37Rv, (ii) Staphylococcus aureus, (iii) Klebsiella pneumoniae, (iv) Escherichia coli, (v) Candida albicans, (vi) Pseudomonas aeruginosa, (vii) Cryptococcus neoformans, (viii) Salmonella typhi, (ix) Shigella sonnei, and (x) Methicillin-resistant S. aureus (MRSA) were investigated by disc diffusion and microdilution techniques. Antituberculous activity was investigated using BACTEC MGIT 960 system while cytotoxicity was analyzed by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on HEp-2 cells. Finally, phytochemicals were screened using standard procedures. RESULTS: Methanolic fractions exhibited a broad spectrum activity inhibiting 75% of test pathogens. It had the highest activity with minimal inhibition concentration (MIC) values of <=62.5 ug/ml recorded against 62.5% tested microbes. It yielded the highest zone of inhibition of 20.3 mm (S. aureus), lowest MIC of <12.5 ug/ml (MTB), and the lowest minimal bactericidal concentration of 62.5 ug/ml (C. albicans), within the acceptable toxicity limit (CC50 >90 ug/ml). The phytochemicals largely believed to be responsible for the observed activity included: Alkaloid, phenols, anthraquinones, terpenoids, and flavonoids. CONCLUSION: Methanolic fraction had remarkable activity against MRSA, S. aureus, E. coli, S. sonnei, C. albicans, and MTB, which are of public health concerns due to drug resistance and as sources of community and nosocomial infections. To the best of our knowledge, this is the first report exploring the antituberculous activity of C. myricoides and thence a major output in search of novel, safe drug leads to mitigate the global tuberculosis threat. PMID- 27366348 TI - Nigerian propolis improves blood glucose, glycated hemoglobin A1c, very low density lipoprotein, and high-density lipoprotein levels in rat models of diabetes. AB - OBJECTIVE: According to our previous studies, propolis of Nigerian origin showed some evidence of hypoglycemic and hypolipidemic activities in addition to its ability to ameliorate oxidative-stress-induced organ dysfunction. This study was carried out to determine whether an ethanolic extract of Nigerian propolis (EENP) improves glycated hemoglobin A1c (HbA1c), fasting plasma glucose, very low density lipoprotein (VLDL), and high-density lipoprotein (HDL) concentrations in rats that have alloxan diabetes. MATERIALS AND METHODS: Diabetes was induced with alloxan (110 mg/kg). Animals were divided into 5 groups (n = 5); Group 1 was non diabetic receiving normal saline and Group 2 was diabetic but also received only normal saline. Groups 3, 4, and 5 were diabetic receiving 200 mg/kg propolis, 300 mg/kg propolis, and 150 mg/kg metformin, respectively, for 42 days. RESULTS: Hyperglycemia, elevated serum level of VLDL, elevated plasma level of HbA1c, and decreased levels of HDL were observed in the diabetic untreated animals. Nigerian propolis decreased blood glucose level and serum level of VLDL but elevated HDL level. These changes were significant (P < 0.05). The levels of plasma HbA1c were also reduced in the propolis-treated groups, and the reduction was significant (P < 0.05). CONCLUSION: Nigerian propolis contains compounds exhibiting hypoglycemic, antihyperlipidemic, and HbA1c reducing activities. PMID- 27366349 TI - Ethnopharmacological studies on the uses of Euphorbia hirta in the treatment of dengue in selected indigenous communities in Pangasinan (Philippines). AB - AIM: Euphorbia hirta is the most widely used plant in the folkloric treatment of dengue in the Philippines. This study documents the anecdotal uses of E. hirta in the treatment of dengue in 3 indigenous communities in Pangasinan from April to June of 2015. MATERIALS AND METHODS: The number of use reports pertaining to symptoms of dengue and other diseases were tallied from 82 informants living in Anda Island, Mt. Colisao and Mt. Balungao. The demographics of the informants as well as the corrected major use agreements (cMUAs) and fidelity levels (FLs) of each reported symptom of dengue were calculated. The major dosage forms used during treatment were also tallied. RESULTS: Respondents, dominated by the age group 60-80 and mostly females with at least primary and secondary education, provided information on the use reports of E. hirta. High FL values and cMUA of at least 35% were obtained for cardinal symptoms of dengue-related to bleeding episodes while low cMUAs (i.e. 2-4%) were obtained for symptoms during the recovery phase. High FL values were obtained for symptoms observed during the febrile phase. The most widely used dosage forms are decoctions of the leaves and barks of E. hirta. CONCLUSION: This study was able to qualify the uses of E. hirta in the treatment of dengue in the 3 communities surveyed. PMID- 27366350 TI - Coconut water of different maturity stages ameliorates inflammatory processes in model of inflammation. AB - AIM: Coconut water is a natural beverage that is a part of daily diet of many people. This study was designed to explore the anti-inflammatory activity of coconut water of different maturation stages (young and mature) with rat paw edema model of inflammation using plethysmometer. METHODOLOGY: For this study, albino rats were selected and divided into four equal groups (10 rats in each group). Group 1 was set as control and administered distilled water 1 ml orally; Groups 2 and 3 were treated with young and mature coconut water, respectively, at 4 ml/100 g dose orally. Group 4 was treated with the standard drug (ibuprofen) at 400 mg/70 kg. 0.1 ml of 1% w/v acetic acid was administered in the subplantar tissue of rat paw 30 min after oral treatments of groups. Plethysmometer was used to measure rat paw edema. RESULTS: Results revealed that both coconut water possess significant anti-inflammatory activity (P < 0.001). In comparison to control, percent inhibition by young coconut water was 20.22%, 35.13%, 42.52%, and 36% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (42.52%) was observed in the second phase of the inflammatory process. On the other hand, percent inhibition by mature coconut water was 18.80%, 25.94%, 24.13%, and 18.66% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (25.94%) was observed in the first phase of the inflammatory process. CONCLUSIONS: This study strongly suggests the use of young coconut water for potent anti-inflammatory effect and mature coconut water for moderate anti-inflammatory effect. PMID- 27366351 TI - Investigation the efficiency of various methods of volatile oil extraction from Trichodesma africanum and their impact on the antioxidant and antimicrobial activities. AB - BACKGROUND: Currently, there is an increasing interest in developing more efficient techniques for the extraction of phytochemicals. Microwaves and ultrasonic extraction methods are promising techniques that can be used for this purpose. OBJECTIVES: The purpose of this study was to investigate the impact of different extraction methods on yield, antioxidant and antimicrobial activities of volatile oil extracted from Trichodesma africanum. MATERIALS AND METHODS: Volatile oil was extracted using microwave, ultrasonic, microwave-ultrasonic, and conventional hydrodistillation methods. The extracted oil was evaluated for antioxidant and antimicrobial activities. The antioxidant activity was assessed by 2,2-Diphenyl-1-picrylhydrazyl scavenging assay, whereas the antimicrobial activity was assessed by broth microdilution method. The antimicrobial activity of the volatile oils was examined against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa American type culture collection reference strains, as well as against methicillin-resistant S. aureus (MRSA) and Candida albicans clinical isolates. RESULTS: The volatile oil obtained by the four extraction methods in this study exhibited both antioxidant and antimicrobial activities. Among the four extraction methods used, the microwave-ultrasonic method yielded the largest amount (1.8% v/w) and the yield exhibited the highest antioxidant activity in terms of inhibition (91.83% +/- 1.1). The minimum inhibitory concentrations for E. coli, P. aeruginosa, S. aureus, MRSA, and C. albicans were 3, 5, 6, 3, and 9, respectively. CONCLUSION: Among the extraction techniques used in this study, the microwave-ultrasonic method showed the best results. Moreover, this study suggests that T. africanum volatile oils contain active substances that could potentially be used both as natural preservatives in food and pharmaceutical industries as well as in developing new antimicrobial and antioxidant agents. PMID- 27366352 TI - Assessment of anti-inflammatory and anti-arthritic properties of Acmella uliginosa (Sw.) Cass. based on experiments in arthritic rat models and qualitative gas chromatography-mass spectrometry analyses. AB - AIM: The principle objective of the study was to explore the anti-arthritic properties of Acmella uliginosa (AU) (Sw.) Cass. flower in a rat model and to identify potential anti-inflammatory compounds derived from flower extracts. The synergistic role played by a combination of AU flower and Aloe vera (AV) gel crude extracts was also investigated. MATERIALS AND METHODS: Male Wistar rats induced with Freund's complete adjuvant (FCA) were used as a disease model of arthritic paw swelling. There were three experimental and two control groups, each consisting of five rats. Paw circumference and serum biochemical parameters were evaluated to investigate the role of the flower extracts in disease amelioration through a feeding schedule spanning 21 days. Gas chromatography/mass spectrometry (GC/MS) analyses were performed to search for the presence of anti inflammatory compounds in the ethanolic and n-hexane solvent extracts of the flower. RESULTS: As a visual cue to the experimental outcomes, FCA-induced paw swelling decreased to the normal level; and hemoglobin, serum protein, and albumin levels were significantly increased in the treated animals. The creatinine level was estimated to be normal in the experimental rats after the treatment. The combination of AU and AV showed the best recovery potential in all the studied parameters, confirming the synergistic efficacy of the herbal formulation. GC/MS analyses revealed the presence of at least 5 anti-inflammatory compounds including 9-octadecenoic acid (Z)-, phenylmethyl ester, astaxanthin, a N-Normethadol, fenretinide that have reported anti-inflammatory/anti-arthritic properties. CONCLUSION: Our findings indicated that the crude flower homogenate of AU contains potential anti-inflammatory compounds which could be used as an anti-inflammatory/anti-arthritic medication. PMID- 27366353 TI - Cryptolepine, an indoloquinoline alkaloid, in the management of diabetes mellitus and its associated complications. AB - BACKGROUND: Effective long-term management is the key to treatment of diabetes mellitus (DM) and its complications. AIM: To ascertain the ability of cryptolepine (CRP) in managing DM and some associated complications. MATERIALS AND METHODS: Changes in fasting blood sugar (FBS), body weight, response to thermally-induced pain, and semen quality were assessed in normal and alloxan induced diabetic rats treated with CRP (10, 30, or 100 mg/kg), glibenclamide (10 mg/kg), or normal saline (2 ml/kg) per os. Hematological profile, liver and kidney function tests, lipid profile, as well as liver, kidney, and pancreas histopathological examinations were also conducted to establish possible effects of CRP treatment. RESULTS: CRP treatment reduced (P <= 0.001) FBS and body weight, inhibited (P <= 0.05 - 0.001) the latency to tail flick or withdrawal from pain stimulus. It did not alter (P > 0.05): Hematological parameters, elevated (P <= 0.05 - 0.001) plasma aspartate transaminase, alanine transaminase, and gamma-glutamyl transferase, reduced (P <= 0.01) plasma urea, and elevated (P <= 0.001) plasma creatinine associated with DM. CRP, however, reversed (P <= 0.05 - 0.001) DM-associated elevation (P <= 0.05 - 0.001) of plasma cholesterol, triglycerides, and low-density lipoproteins, and the reduction in high-density lipoproteins. CRP (10-30 mg/kg) showed dose-dependent regeneration of beta-islet cells but could not repair degenerated liver and kidney tissue. CRP worsens dose dependently (P <= 0.001) reduced sperm quality associated with DM. CONCLUSION: CRP abolishes hyperglycemia, weight loss, cold allodynia, neuropathic pain, and hyperlipidemia as well as pancreatic beta-islet cell damage associated with DM. It, however, does not improve liver and kidney damage and lowered semen quality. PMID- 27366354 TI - Low dose effects of a Withania somnifera extract on altered marble burying behavior in stressed mice. AB - AIM: Withania somnifera root (WSR) extracts are often used in traditionally known Indian systems of medicine for prevention and cure of psychosomatic disorders. The reported experiment was designed to test whether low daily oral doses of such extracts are also effective in suppressing marble burying behavior in stressed mice or not. MATERIALS AND METHODS: Groups of mice treated with 10, 20, or 40 mg/kg daily oral doses of WSR were subjected to a foot shock stress-induced hyperthermia test on the 1(st), 5(th), 7(th), and 10(th) day of the experiment. On the 11(th) and 12(th) treatment days, they were subjected to marble burying tests. Stress response suppressing effects of low dose WSR were estimated by its effects on body weight and basal core temperature of animals during the course of the experiment. RESULTS: Alterations in bodyweight and basal core temperature triggered by repeated exposures to foot shock stress were absent even in the 10 mg/kg/day WSR treated group, whereas the effectiveness of the extract in foot shock stress-induced hyperthermia and marble burying tests increased with its increasing daily dose. CONCLUSION: Marble burying test in stressed mice is well suited for identifying bioactive constituents of W. somnifera like medicinal plants with adaptogenic, anxiolytic and antidepressant activities, or for quantifying pharmacological interactions between them. PMID- 27366357 TI - The consumption of propolis and royal jelly in preventing upper respiratory tract infections and as dietary supplementation in children. AB - Propolis and royal jelly (RJ), two important honeybee products, have been used commonly all over the world as traditional and ethnopharmacological nutrients since ancient times. Both of them have a lot of active ingredients which are known to be effective for several medical conditions. In this article, medical databases were searched for the usage of RJ and propolis in upper respiratory tract infections (URTI) and as a dietary supplementation, together and separately. 10-hydroxy-2-decenoic acid is the most prominent active compound showing antimicrobial effect within RJ. Caffeic acid phenethyl ester is the most famous one that shows antimicrobial and anti-inflammatory effect within propolis. When compared with propolis, RJ was found to have richer content for all three main nutrients; proteins, carbohydrates, and lipids. More clinical, experimental, and basic studies are needed to find out the best standardized mixture to cope with URTI in which RJ and propolis will be main ingredients in addition to the other secondary compounds that have health-beneficial effects. PMID- 27366356 TI - Therapeutic significance and pharmacological activities of antidiarrheal medicinal plants mention in Ayurveda: A review. AB - Diarrhea is a serious problem affecting 3-5 billion people per year around the world, especially children of below 5 years. 70% of the world population uses traditional and indigenous medicine for their primary health care. The facts of these indigenous remedies are passed verbally and sometimes as documents. Since ancient time, Ayurveda is the main system of healing in South East Asian countries. Indian literature from ayurvedic texts and other books claim the potency of several plants in the treatment of diarrhea. As the global prospective of ayurvedic medicine is increasing, interest regarding the scientific basis of their action is parallely increasing. Researchers are doing experiments to establish the relation between the claimed action and observed pharmacological activities. In the present article, an attempt was made to compile the scientific basis of medicinal plants used to cure diarrhea in Ayurveda. Literature was collected via electronic search (PubMed, ScienceDirect, Medline, and Google Scholar) from published articles that reports antidiarrheal activity of plants that were mentioned in Ayurveda classics. A total of 109 plant species belonging to 58 families were reported for their antidiarrheal activity. Several Indian medicinal plants have demonstrated promising antidiarrheal effects, but the studies on the antidiarrheal potentials of these plants are not taken beyond proof of concept stage. It is hoped that the article would stimulate future clinical studies because of the paucity of knowledge in this area. PMID- 27366355 TI - Anti-fibro-hepatocarcinogenic Chinese herbal medicines: A mechanistic overview. AB - Chinese herbal medicine (CHM) is an integral component of complementary/alternative medicine and it is increasingly becoming the preferred therapeutic modality for the treatment of liver fibrosis and hepatocellular carcinoma (HCC) worldwide. Accordingly, the World Health Organization (WHO) has attested to the popularity and efficacy of indigenous herbal therapies including CHM as a first line of treatment for some diseases including liver disorders. However, the WHO and drug discovery experts have always recommended that use of indigenous herbal remedies must go hand-in-hand with the requisite mechanistic elucidation so as to constitute a system of verification of efficacy within the ethnobotanical context of use. Although many CHM experts have advanced knowledge on CHM, nonetheless, more enlightenment is needed, particularly mechanisms of action of CHMs on fibro-hepato-carcinogenesis. We, herein, provide in-depth mechanisms of the action of CHMs which have demonstrated anti-fibro hepatocarcinogenic effects, in pre-clinical and clinical studies as published in PubMed and other major scientific databases. Specifically, the review brings out the important signaling pathways, and their downstream targets which are modulated at multi-level by various anti-fibro-hepatocarcinogenic CHMs. PMID- 27366358 TI - Trends and challenges toward integration of traditional medicine in formal health care system: Historical perspectives and appraisal of education curricula in Sub Sahara Africa. AB - The population residing Sub-Sahara Africa (SSA) continues to suffer from communicable health problems such as HIV/AIDS, malaria, tuberculosis, and various neglected tropical as well as non-communicable diseases. The disease burden is aggravated by shortage of medical personnel and medical supplies such as medical devices and minimal access to essential medicine. For long time, human beings through observation and practical experiences learned to use different plant species that led to the emergence of traditional medicine (TM) systems. The ancient Pharaonic Egyptian TM system is one of the oldest documented forms of TM practice in Africa and the pioneer of world's medical science. However, the medical practices diffused very fast to other continents being accelerated by advancement of technologies while leaving Africa lagging behind in the integration of the practice in formal health-care system. Challenging issues that drag back integration is the development of education curricula for training TM experts as the way of disseminating the traditional medical knowledge and practices imbedded in African culture. The few African countries such as Ghana managed to integrate TM products in the National Essential Medicine List while South Africa, Sierra Leone, and Tanzania have TM products being sold over the counters due to the availability of education training programs facilitated by research. This paper analyses the contribution of TM practice and products in modern medicine and gives recommendations that Africa should take in the integration process to safeguard the SSA population from disease burdens. PMID- 27366359 TI - On the use of carnosine and antioxidants: A letter from Russia. PMID- 27366360 TI - Perioperative Temperature Monitoring and Patient Warming: A Survey Study. AB - OBJECTIVE: Hypothermia is defined as the decrease of core body temperature under 36 degrees C. Hypothermia is observed at a rate of 50-90% in the perioperative period. In our study, we aimed to measure the perception of hypothermia in our country, to evaluate the measures taken by physicians to intercept hypothermia, to determine the frequency and the methods used to monitor body temperature and the techniques used in warming the patients. Another aim was to develop a guideline for preventing perioperative hypothermia. METHODS: The questionnaire consisted of 26 multiple-choice questions. The time needed to answer the questions was 8-10 minutes. RESULTS: Of the 1380 individuals, 312 (22.6%) answered the questions in the questionnaire. Of these, 148 (47.4%) declared they were working in university hospitals, 80 (25.6%) in training and research hospitals, 51 (16.4%) in government hospitals and 33 (10.6%) in various private hospitals. Of the 312 individuals, 134 (42.9%) were specialists, 107 (34.3%) were resident physicians, 71 (22.8%) were academics. In addition, 212 (67.9%) reported working in operating rooms, 49 (15.7%) in intensive care units and 42 (13.5%) both in operating rooms and intensive care units. In the answers, there was variation among the hospital types in applications of body temperature monitoring and warming the patient. Another finding was that the individuals had different approaches to the concepts on perioperative hypothermia and its consequences. CONCLUSION: The perceptions of physicians and the allied health personnel in government and private hospitals should be enhanced by informing them about the passive and active heating systems to prevent hypothermia. Although the situation in university and training and research hospitals seems to be better, defects are still observed in practice. Preparation of a national guideline for prevention of perioperative hypothermia is needed. PMID- 27366361 TI - A Comparison of the Effects of Esmolol and Dexmedetomidine on the Clinical Course and Cost for Controlled Hypotensive Anaesthesia. AB - OBJECTIVE: To compare the effects of esmolol (beta-blocker) and dexmedetomidine (alpha-2-agonist) on patients' clinical course and cost of application of controlled hypotension during middle-ear surgery. METHODS: Fifty ASA I-II patients scheduled for tympanomastoidectomy were enrolled in the study and were randomized into two groups. Bispectral Index (BIS) and neuromuscular monitoring (TOF GUARD-SX) were applied to all patients. In group E (n=25), 0.5 mg kg(-1) min(-1) esmolol was infused over 1 min before induction and titrated over a range of 10-200 MUg kg(-1) min(-1); in group D (n=25), 0.5 MUg kg(-1) dexmedetomidine was infused over 10 minutes before induction, and then titrated over a range of 0.2-0.7 MUg kg(-1) hr(-1) to maintain mean arterial pressure (MAP) between 55 and 65 mmHg and BIS 40-50 after induction. In both groups, 0.25 MUg kg(-1) min(-1) remifentanil infusion was used for anaesthesia maintenance. Maintaining end-tidal CO2 (EtCO2) at 35-40, using 1 MAC sevoflurane in 50% O2-air mixture, mechanical ventilation was started. The effects of both agents on hemodynamic conditions [(heart rate (HR), mean arterial pressure (MAP)], neuromuscular blockage [onset of action (OA), duration of clinical action (DCA), recovery index (RI)], amount of bleeding, surgeon satisfaction, and total dexmedetomidine and esmolol doses used during the intervention were recorded and costs were compared between the groups. RESULTS: No significant difference was present in hemodynamic conditions, bleeding scores or surgeon satisfaction between groups. Although OA was similar in both groups, DCA and RI were significantly higher in group D. Cost was significantly higher with esmolol than dexmedetomidine. CONCLUSION: We conclude that although both agents are feasible in inducing hypotensive anaesthesia, while neuromuscular block time prolonged by using dexmedetomidine, higher costs were observed with esmolol. PMID- 27366362 TI - Comparison of the Effects of Different Concentrations of Rocuronium on Injection Pain and Hemodynamics Using Isolated Forearm Technique. AB - OBJECTIVE: We aimed to evaluate Visual-Analogue-Scale (VAS) scores, hand withdrawal, rash and skin eruptions after injections of different concentrations of rocuronium in intubation doses in alert patients using the isolated-forearm technique. METHODS: Eighty ASA I-II patients were included in a randomized, controlled, single-blinded study. Two 20 G cannulas were inserted into the dorsum of the left and right hand in each patient. A tourniquet was applied to the left arm and inflated to 50 mm Hg above the patient's systolic blood pressure. Group 1 (n=20) received 2.5 mg mL(-1) rocuronium diluted with 0.9% NaCl, Group 2 (n=20) received 5 mg mL(-1) rocuronium diluted with 0.9% NaCl, Group 3 (n=20) received 10 mg mL(-1) rocuronium and 0.4 mg mL(-1) lidocaine mixture, and Group 4 (n=20) received 10 mg mL(-1) rocuronium via a cannula on the left hand, provided that a dose of 0.6 mg mL(-1) were given to all groups of patients. VAS0-VAS60 values, hand-withdrawal, rash and skin eruptions were assessed in patients who were administered rocuronium but not under the effects of hypnotic or neuromuscular agents. Hemodynamic values were recorded both before and after the administration of hypnotic-neuromuscular agents. RESULTS: VAS0 values were significantly higher in Group 4 when compared to Groups 1, 2 and 3 (p=0.032). No significant difference was observed between VAS0 and VAS60 values in Groups 1, 2 and 3. In Group 4, VAS0 values were significantly higher than VAS60 values (p=0.003). No significant difference was observed between groups in terms of side effects and hemodynamic values. CONCLUSION: In conclusion, we determined that using rocuronium diluted with 0.9% NaCl was more effective in preventing injection pain than using a rocuronium-lidocaine mixture. PMID- 27366363 TI - Assessment of the Ability of Anaesthetists to Locate the Internal Jugular Vein by the Anatomic Landmark Technique with Ultrasonography: Right or Left, Does it Make any Difference? AB - OBJECTIVE: To assess senior and junior anaesthetists' ability to locate the right and left jugular vein (IJV) using the anatomic landmark technique. METHODS: A total of 45 anaesthetists were included in this study. Initially, a questionnaire assessing the experiences of the anaesthetists was completed. The anaesthetists were grouped into two groups, junior and senior. The anaesthetists, who were blind to the screen, were asked to point to the internal jugular vein bilaterally on the neck of a healthy volunteer using an ultrasound probe with the midpoint as an 'imaginary needle'. The success rates for locating the right and left IJV in both junior and senior groups were assessed separately. RESULTS: The success rate for locating the right IJV was 88% (n=26, 23/26) in the senior and 68.4% (n=19, 13/19) in the junior group (p<0.001). The success rate for locating the left IJV was 69% (18/26) in the senior and 78% (15/19) in the junior group (p<0.001), while the difference in success rates for locating the right and left IJV in the senior group was found to be statistically significant (p<0.001). CONCLUSION: Both use of the anatomic landmark technique and experience increased the success rate. Especially in the less preferred left IJV catheterization, use of the anatomic landmark technique independent of the experience factor could increase the success rate. PMID- 27366364 TI - Comparison of Parasacral and Posterior Sciatic Nerve Blocks Combined with Lumbar Plexus Block. AB - OBJECTIVE: The aim of this study is to compare the effects of parasacral and posterior Winnie approaches when combined with the inguinal paravascular approach for lumbar plexus block. METHODS: After the approval of the Ethics Committee, 40 patients scheduled to undergo arthroscopic knee surgery were enrolled. The patients were randomly assigned into two groups in a double-blind manner to perform sciatic nerve block either by the parasacral technique (Group I) or by the posterior approach (Group II). RESULTS: The obturator nerve motor block success rate was found to be 80% (16/20) in Group I, whereas it was 10% (2/20) in Group II (p<0.05). CONCLUSION: Inguinal paravascular block with parasacral sciatic nerve block led to a much higher incidence of obturator nerve motor block when compared to the inguinal paravascular block with posterior sciatic nerve block during knee arthroscopies. PMID- 27366365 TI - Anaesthesia for Caesarean Section of Pregnant Women with Idiopathic Thrombocytopenic Purpura. AB - Women with idiopathic thrombocytopenic purpura (ITP) may become pregnant, or the disease may occur for the first time during pregnancy. Thrombocytopenia is usually noticed in the first months of pregnancy and the platelet count is often quite low. In this case report, we described the anaesthetic method for caesarean section in a pregnant woman at 38 weeks of gestation with refractory ITP. PMID- 27366366 TI - Anaesthesia for Caesarean Delivery in a Pregnant with Acute Type B Aortic Dissection. AB - About 50% of aortic dissections in women younger than 40 years occur during pregnancy; mostly in the 3rd trimesters and postpartum period. Aortic dissection in pregnancy creates a serious mortality risk for both mother and the foetus. The ultimate goal is to ensure the safety of both the mother and the foetus. In such cases, the best method of anaesthesia for caesarean delivery is still controversial. The first aim of anaesthetic management is to reduce the effect of cardiovascular instability on the dissected aorta. Here, we report the anaesthetic management of a 36 year-old pregnant woman who developed acute type B aortic dissection in the 30(th) gestational weeks and scheduled for caesarean section. Since hemodynamic stability could not be achieved despite nitro glycerine and esmolol infusions, together with invasive arterial monitoring, the decision for caesarean delivery was taken. A team of Cardiovascular Surgeons and an operating room were prepared because of the risks of aortic rupture and hemodynamic collapse during operation. Combined-spinal epidural anaesthesia was administered using 5 mg hyperbaric bupivacaine and 20 MUg fentanyl given at the L3-4 spinal level in the side lying position. After achieving T4 sensory block level, the operation proceeded and a baby weighing 1432 grams was delivered in 4 min with a median subumbilical incision. Epidural patient controlled analgesia was applied to the patient during follow-up with medical treatment at postoperative period. In pregnant women with acute Type B aortic dissection, if adequate sensory block level cannot be achieved despite using a combination of low dose local anaesthetic (spinal use) and opioids, we are in the opinion that combined spinal-epidural anaesthesia, which allows the use of additional doses can be a decent choice. PMID- 27366367 TI - Awake Fibreoptic Intubation for Forearm Injury in a Patient with Occipito Cervical Fixator. AB - A 23-year-old male patient with occipitocervical fixator was scheduled for surgery due to injury to the right forearm. The patient's thyromental distance was 5 cm, mouth opening grade II, sternomental distance 10 cm and Mallampati score 4. Loss of extension and rotation movements of the head was assessed as difficult intubation criteria. Anaesthetic procedures are almost always difficult in patients with occipitocervical fixation; the limited cervical extension complicated both intubation and ventilation. In this report, application of general anaesthesia using awake fibreoptic bronchoscopic intubation (FOB) is described. After routine monitoring of vital signs and premedication, hypopharyngeal topical anaesthesia was accomplished by instilling 10% lidocaine spray twice via the appropriate nostril. Superior laryngeal nerve block was performed with local anaesthetic infiltration of tissues 1 cm below the greater horns of the hyoid bone. Lingual and pharyngeal branches of the glossopharyngeal nerve were blocked. Transtracheal block was performed. Following completion of local anaesthesia, the patient was intubated using the awake FOB technique, on 5 L min(-1) of 100% O2. After muscle relaxation, the patient underwent a microsurgical operation to repair eight tendons, one artery, and one nerve. Surgery lasted for 5 hours. When the extubation criteria were met, the patient was extubated. In cases of occipitocervical fixation, which causes severe limitation of neck movements, the use of awake fibreoptic intubation should be considered. PMID- 27366368 TI - Anaesthetic Management of a Neonate with Giant Cystic Hygroma. AB - Cystic hygroma, which originates from embryonic lymphoid tissue, is a benign tumour without any potential for malignancy. It is commonly located in the neck area. Anaesthetic management of a large neck mass may be challenging due to difficulty in intubation and the severe haemodynamic effects of surgical removal of a giant tumour. Serious consequences such as sudden airway occlusion resulting in hypoventilation and hypoxemia may arise. We present the anaesthetic management of a 15-day-old infant who underwent surgical removal of a cystic hygroma located on the left side of the neck. Anaesthesia was induced by mask ventilation with sevoflurane in 100% oxygen and intubation was carried out while maintaining spontaneous ventilation. The endotracheal tube was sutured to the tip of the right lip to avoid movement or extubation. In addition to arterial cannulation for invasive blood pressure monitoring, central venous catheterization for perioperative fluid management was put in place. After 6 hours of surgery, the infant was transported to the neonatal intensive care unit and was extubated without difficulty the next day. Facial nerve injury was observed to be temporary. PMID- 27366369 TI - The Turkish Anaesthesiology and Reanimation Society Guidelines for the prevention of inadvertent perioperative hypothermia. PMID- 27366370 TI - Can we Improve Outcome in High Risk Surgery? AB - Despite the small number of high-risk surgical patients in comparison to all surgical patients, they account for the largest proportion of overall perioperative mortality. Goal directed hemodynamic support may result in a lower incidence of complications and reduced length of hospital stay in these patients. Beyond the standard monitoring of circulation, such as blood pressure and heart rate, further parameters and procedures such as pulse pressure/stroke volume variation-, stroke volume/cardiac index-, and central venous oxygen saturation guided resuscitation may improve the outcome of high-risk surgical patients. The aim of this review is to focus on the results of animal and clinical studies investigating the usefulness of these indices in the context of goal-directed perioperative support. PMID- 27366371 TI - Comparison of Dexmedetomidine and Midazolam in Sedation for Percutaneous Drainage of Hepatic Hydatid Cysts. AB - OBJECTIVE: Hydatid cyst still continues to be a public health problem. The basic treatment for the disease is surgery, but ultrasound-guided percutaneous drainage has become an important treatment alternative. Agents preferred for sedation during drainage performed under local anaesthesia must also preserve respiration and hemodynamic stability while providing adequate sedation. We compared the sedative properties of midazolam, which has a short duration of action, and a selective alpha2 adrenergic receptor agonist, dexmedetomidine, and the intraoperative complications. METHODS: After approval by the clinical trials ethics committee, 40 patients with similar demographic data were randomized into two groups. All patients received 10 mg metoclopramide and 45.5 mg pheniramine before the procedure. Then, midazolam (0.07 mg kg(-1) IV bolus followed by 0.01 mg kg(-1) h(-1) infusion) was administered to Group 1, and dexmedetomidine (1 MUg kg(-1) loading dose in 10 minutes, followed by 0.2 MUg kg(-1) h(-1) continuous infusion) was administered to Group 2 for sedation. Just before the surgical procedure, all patients received IV propofol in a subhypnotic dose of 0.5 mg kg( 1); the dose was repeated if adequate sedation could not be achieved. Observer's assessment of alertness/sedation (OAA/S) scale and Bispectral index (BIS) were used to evaluate the sedation level during the procedure. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), peripheral oxygen saturation (SpO2) and end-tidal carbon dioxide pressure (ETCO2) were monitored before and after induction and every 5 minutes thereafter. Propofol requirement was noted for each group. RESULTS: Sedation in the dexmedetomidine group was as effective and adequate as that observed in the midazolam group. BIS values were significantly lower in the dexmedetomidine group, especially after 10 minutes and thereafter. RR, SpO2, and ETCO2 were similar in both groups, whereas clinically insignificant decreases in HR and MAP were observed in the dexmedetomidine group. Propofol requirements were similar in both groups. CONCLUSION: We conclude that dexmedetomidine, providing adequate sedation without respiratory depression, can be considered as an appropriate agent for sedation in surgical procedures performed under local anaesthesia. PMID- 27366372 TI - The Effect of Different End-tidal Desflurane Concentrations on Bispectral Index Values in Normal Children and Children with Cerebral Palsy. AB - OBJECTIVE: In this study, we aimed to compare the effects of different intraoperative end-tidal desflurane concentrations on bispectral index (BIS) values in normal children and children with cerebral palsy. METHODS: Twenty normal children (Group N) and 20 children with non-communicative/nonverbal cerebral palsy (Group CP), between 2 and 15 years of age, undergoing elective orthopaedic surgery were included in the study. Following premedication with midazolam, anaesthesia was induced by infusing 1% propofol at a rate of 200 mL hr(-1) until BIS reached 50. Heart rate, blood pressure and BIS values were recorded before and after the induction of anaesthesia, at steady-state end-tidal concentrations of 4% and 6% desflurane, and after emergence from anaesthesia. A p value <0.05 was considered significant in the statistical analyses, including Kolmogorov-Smirnov, t-test, paired samples t-test and chi-square test. RESULTS: The time to extubation and eye opening after discontinuation of anaesthesia was longer in Group CP. BIS values before the induction of anaesthesia, at a steady state end-tidal desflurane concentration of 4% and after emergence from the anaesthetic were significantly lower in Group CP. At a steady-state end-tidal desflurane concentration of 6%, BIS values were slightly lower in Group CP but this difference was not statistically significant. CONCLUSION: Based on the data obtained, we concluded that BIS monitoring in children with cerebral palsy can be useful in terms of decreasing adverse effects and drug interactions due to multiple drug usage by reducing the use of anaesthetic agents and improving emergence from the anaesthetic. PMID- 27366373 TI - Comparison of the Effects of Remifentanil and Dexmedetomidine Infusions on Hemodynamic Parameters and Thyroid Hormones. AB - OBJECTIVE: In this study, we compared the effects of remifentanil and dexmedetomidine on hemodynamic parameters, inhalation agent consumption and thyroid hormone levels at the late postoperative period. METHODS: Forty-five euthyroid ASA I-II patients between 20 and 75 years of age were randomly assigned into three groups: During induction, Group R received 1.0 mcg kg(-1) remifentanil as slow bolus in two minutes,Group D received 1.0 mcg kg(-1) dexmedetomidine in 10 minutes as infusion,Group C received 1.0 mcg kg(-1) fentanyl as bolus. Afterwards, all patients received 2.0 mg kg(-1) propofol and 0.2 mg kg(-1) cisatracurium for induction.For anaesthesia maintenance during and up to 15 minutes before the end of the surgery; Group R received 0.05 mcg kg(-1) min(-1) remifentanil,Group D received 0.5 mcg kg(-1) h(-1) dexmedetomidine infusion.During the surgery, heart rate, mean arterial pressure and end-tidal sevoflurane concentrations were recorded for every patient. Venous blood samples were taken after the operation, at postoperative 24(th) hour and postoperative 5(th) day and the variations in fT3, fT4, TSH levels were analyzed. RESULTS: Mean arterial pressure values and sevoflurane consumption were lower in Group R and Group D in comparison with the control group. In comparison between groups, the decrease in fT3 values at postoperative 24(th) hour was more significant in the control group than the other two groups. CONCLUSION: We suggest that, both agents suppress the hemodynamic response, decrease the consumption of inhalation agents and cause less change in the levels of thyroid hormones, which can be considered as one of the indicators of endocrine response. PMID- 27366374 TI - The Effects of Bispectral Index and Neuromuscular Blockade Monitoring on the Depth of Anaesthesia and Recovery in Cardiac Patients Under Desflurane Anaesthesia. AB - OBJECTIVE: In this study, we aimed to investigate the effects of bispectral index (BIS) and neuromuscular blockade monitoring on the depth of anaesthesia and recovery in cardiac patients, scheduled to undergo open cholecystectomy operation with desflurane anaesthesia. METHODS: After the approval of the Ethics Committee and consent from the patients, patients were randomly divided into two groups. All patients received standard induction drugs, and 4-6% desflurane was used for maintenance of anaesthesia. In Group I, the anaesthesiologist was blind to BIS, and end-tidal volatile agent concentration (ETVAC) of desflurane was titrated according to the patients' hemodynamic changes. In Group II, ETVAC of desflurane was titrated to maintain BIS at 50-60. The hemodynamic data, BIS values, end tidal volatile agent concentration (ETVAC) and train of four (TOF) values were recorded at pre-induction, post-induction, post-intubation, 1st and 5th minutes after surgical incision and then every 15 min. At the end of the operation, extubation time and the time to reach an Aldrete recovery score >=9 were recorded in each group. Additionally, neuromuscular agent and narcotic agent doses were recorded. RESULTS: The BIS values were lower for Group I in all times, except pre and post-induction times (p<0.05). ETVAC values of all times were lower for Group II (p<0.05). CONCLUSION: The requirement of volatile agent, which was given according to BIS monitoring, was lower than in the standard technique, but it is considered not to affect the early extubation, recovery and neuromuscular agent requirement dependent on TOF monitoring. PMID- 27366375 TI - Evaluation of Early Warning Scoring System and Nursing Guide Application in Post Anaesthesia Care Unit. AB - OBJECTIVE: To determine the effect of nursing guide application developed for the present study and to evaluate the Early Warning Scoring System (EWSS) in post anaesthesia care unit (PACU). METHODS: The study was carried out as a randomised controlled experimental study. The study sample comprised of 123 adult patients having thoracic and abdominal surgery between January 2011 and April 2011 in the Anaesthesiology and Reanimation Department of a training and research hospital. Patients were randomised during the pre-operative period; the patients who were followed-up according to the EWSS and a nursing guide constituted the study group (SG=63) and the patients whose EWSS score was calculated but routine follow-up in PACU was not intervened constituted the control group (CG=60). RESULTS: During the PACU, complications developed in in 34.92% of SG patients and in 30.00% of CG patients. Of the SG patients, 95.45% developing complications and of the CG patients, 22.22% developing complications were treated in the first 10 minutes, and it was determined that in 61.12% of CG patients, complications were not treated. There was a significant difference between the SG and CG patients in terms of treatment duration against complications (p<0.05). CONCLUSION: The EWSS and nurse's guide provides early determination and treatment of patients developing complications. Thus, it is recommended to use the EWSS and a nursing guide in PACU. PMID- 27366376 TI - Monitoring Cardiac Output and Transesophageal Echocardiography during Removal of a Ventricular Assist Device. AB - A ventricular assist device (VAD) is a mechanical pump used to support heart function and blood flow in patients with poor heart functions. For selected patients who are too ill to wait for a heart transplant or are not eligible for a heart transplant because of age or other medical problems, ventricular assist devices offer life-saving therapy. This device has also become a life-saving approach for patients with acute viral myocarditis. Following the acute illness phase, when heart function has improved, the VAD is carefully removed. It is very important to continuously monitor myocardial functions during this period. In this paper, we present a patient who underwent cardiac output and transesophageal echocardiography monitoring during VAD removal. PMID- 27366377 TI - Anticholinergic Toxic Syndrome Caused by Atropa Belladonna Fruit (Deadly Nightshade): A Case Report. AB - Atropa Belladonna poisoning may lead to anticholinergic syndrome. Ingestion of high amounts of the plant may cause lethargy, coma, and even a serious clinical picture leading to death. In this case report, we aimed to present a case with anticholinergic syndrome that developed after ingestion of the fruit called "Deadly Nightshade" in our country. PMID- 27366378 TI - The role of cultural interaction in Tianeptine Abuse and Different Tianeptine Application Methods. AB - Tianeptine is a selective serotonin reuptake enhancer, possessing strong antidepressant and anxiolytic properties. Its relative lack of sedative, anticholinergic and cardiovascular side effects makes it a highly tolerable substance of abuse. However, physical dependence quickly develops and withdrawal symptoms are common. Abusers in Georgia and Armenia use tianeptine by intravenous injection. Drug abusing behaviour usually starts during puberty, since it stems from psychological, social and cultural circumstances. Sociodemographic studies show that drug abusing behaviour in Turkey varies according to region and substance. This paper investigates differences between Georgian foreigners and the local population in the eastern Black Sea region in terms of tianeptine abuse and discusses complications resulting from intravenous injection of tiapentine. PMID- 27366379 TI - Submental Orotracheal Intubation in Maxillofacial Fracture Surgery: Report of Two Cases. AB - Two patients, aged 18 and 28 years, with maxillofacial trauma due to motor vehicle accident, were operated upon by a team of plastic surgeons. In this report we aimed to present our experience with submental intubation procedure in these cases, in which orotracheal or nasotracheal intubation was impossible due to panfacial fracture. PMID- 27366380 TI - Teaching Our Students, Our Residents and Ourselves. AB - Even though postgraduate medical education has been the focus of interest in anaesthesiology education, in a broader sense the entire medical community can be considered appropriate learners of anaesthesiology. Anaesthesiologists are equipped to teach physiology, pharmacology, resuscitation, pain management, perioperative assessment, and medical technology. For residency training, an approach based on competencies, skills and professionalism should be used instead of the traditional "apprenticeship" model. When teaching ourselves as qualified anaesthesiologists, areas of continuing professional development, academic career training and continuing medical education should be taken into account. Whereas the responsibility for undergraduate medical education rests with university medical schools, postgraduate medical education is carried out by universities and/or the national health authorities/services. Establishment of partnerships between health-care services and universities should be central to the provision of postgraduate education so as not to dissociate various stages of education. When determining educational strategies, institutional preferences, target populations and their learning styles should be taken into account. To this end, especially for high risk situations simulation-based approaches, scenarios, standardized patients, research, mentoring, journal clubs, seminars, lectures, case discussions, bed-side discussions, courses, games and portfolios have been and are being used widely. Departments of anaesthesiology should establish and maintain a strong presence in undergraduate medical education. Besides being good clinicians, anaesthesiologists should understand all aspects of education and educational outcome in order to better teach students, residents and themselves. Quality of education and the teaching environment should continually be evaluated within the context of quality assurance. PMID- 27366381 TI - Comparison of Different Induction Doses of Rocuronium and Vecuronium in Neuroanaesthesia Practice. AB - OBJECTIVE: To evaluate the efficiency of use of rocuronium and vecuronium in different dose regimens in neuroanaesthesia practice in terms of intubation time and first additional dose requirement. METHODS: Sixty-eight neurosurgery patients with intracranial mass that were operated on were included in our study. Patients were randomly divided into 4 groups according to the induction dose of neuromuscular blocker (NMB) as: Group 1: Vecuronium 0.1 mg kg(-1), Group 2: Priming, 20% of total vecuronium (0.1 mg kg(-1)) needed for induction injected 5 minutes before induction and then the rest used for induction, Group 3: Rocuronium group: 0.6 mg kg(-1), Group 4: Rocuronium with rapid-sequence induction dose (RSID) (1.2 mg kg(-1)). TOF (Train of four) test was used to decide on intubation and an additional NMB dose during surgery. Intubation quality, time from induction to intubation, time until the first additional NMB dose and subsequent NMB dose intervals were recorded. RESULTS: The RSID of rocuronium provided a significantly shorter time period for intubation against the other groups. Also, the time period from induction to first additional NMB requirement was significantly longer in the RSID group than the others. There were no statistically significant differences between the groups' in terms of time period for monitorisation, positioning and start of surgery. CONCLUSION: With the use of RSID of rocuronium, it was seen that excellent intubation quality is provided at around 1 minute and, with its longer duration of action until a first additional dose, it covers the time period for monitorisation, positioning and start of surgery. Because of these effects, we think that RSID of rocuronium may be a better choice of dose regimen for neuroanaesthesia practice. PMID- 27366382 TI - Effects of Ketamine-Propofol Mixture on Intraocular Pressure and Haemodynamics in Elderly Patients: A Randomised Double-Blind Trial. AB - OBJECTIVE: The aim of this study was to compare the effects of a ketamine propofol mixture (ketofol) and propofol on intraocular pressure (IOP) and haemodynamics in elderly patients during anaesthetic management at each repeated measurement times. METHODS: Forty elderly ASA I and II patients were divided into two random groups and received either propofol (1.5 mg kg(-1); group P, n=20) or ketofol (1:1 single syringe mixture of 5 mg mL(-1) ketamine and 5 mg mL(-1) propofol; group KP, n=20). A proseal laryngeal mask airway (PLMA) was inserted 60 seconds after induction of anaesthesia. IOP, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) values were recorded at preinduction (t0), immediately following induction (t1), and at 1 (t2), 3 (t3), and 5 (t4) minutes after induction. Haemodynamic complications and the need for ephedrine were also recorded. RESULTS: Patient characteristics at the beginning of the procedure were similar between the groups. SBP and HR were significantly increased in group KP compared to group P at t1 and t4 (p=0.044). Induction of both anaesthetic agents significantly decreased the IOP values from the t0 (p=0.026). A significant decrease in IOP was found at t1 and t4 in group P compared to group KP (p=0.018). The total dose of ephedrine was statistically different in group P (p=0.034). CONCLUSION: Ketofol can be an alternative agent to provide haemodynamic stability with a moderate decrease in IOP during anaesthesia induction in elderly patients. PMID- 27366383 TI - Evaluation of a Multimodal Approach to Postoperative Pain in Patients Undergoing Flank Incision in the Urology Operating Room. AB - OBJECTIVE: In this study, we evaluated subcutaneous (sc) morphine in combination with multimodal analgesia for postoperative pain control after radical nephrectomy and pyeloplasty with flank incision. METHODS: Forty-nine patients under The American Society of Anesthesiologists Physical Status classification (ASA) I-III aged 18-85 years undergoing radical nephrectomy and pyeloplasty with flank incision were included in this prospective, randomised study. The patients were divided into two groups (Group O [n=25] and Group M [n=24]) and received standard general anaesthesia. Tramadol (100 mg) and paracetamol (100 mg) were given intravenously before fascia closure and 20 mL of 0.25% levobupivacaine was injected locally at surgical incisions in all patients. Patients in Group M also received 0.1 mg kg(-1) morphine subcutaneously. Patient-controlled analgesia (PCA) with tramadol was used for postoperative pain control in both groups. Postoperative pain scores (VAS), vital parameters, side effects, the need for rescue analgesia during 24 hours postoperatively, and patient satisfaction were recorded. RESULTS: Groups were comparable with respect to demographic data, ASA status, and duration of surgery. There were no significant differences between the groups in postoperative PCA tramadol consumption, rescue analgesia, side effects, or vital parameters. Postoperative pain scores (VAS) in Group M were significantly lower at 30, 45, 60, and 120 minutes compared to Group O (p<0.05). CONCLUSION: In patients undergoing radical nephrectomy and pyeloplasty with flank incision, subcutaneous morphine in combination with multimodal analgesia decreases early postoperative pain scores compared to multimodal analgesia alone. PMID- 27366384 TI - Comparison of Maternal and Neonatal Effects of Combined Spinal Epidural Anaesthesia in Either the Sitting or Lateral Position During Elective Cesarean Section. AB - OBJECTIVE: Our goal was to demonstrate which position would be hemodynamically and technically better by comparing the effects of combined spinal epidural (CSE) in the sitting or lateral decubitus position for elective cesarean deliveries on maternal and neonatal parameters and ephedrine requirement. METHODS: Sixty parturients were randomly assigned into two groups to perform CSE in the sitting (Group I, n=30) or right lateral decubitus position (Group II, n=30) using hyperbaric 10 mg bupivacaine and 20 MUg fentanyl. Mean arterial pressure (MAP), heart rate (HR), and characteristics of sensory and motor block were recorded from intrathecal drug administration until the end of surgery. Ephedrine and 1(st) analgesic requirement, number of attempts to perform CSE, incidence of paresthesia during spinal needle insertion, and Apgar scores were recorded. RESULTS: Ephedrine requirements and HR changes were similar in both groups. However, MAP values at 45 min in Group II were significantly less than in Group I. Maximum sensory block levels in Group II were significantly higher than in Group I. Despite similar motor block recovery times in both groups, regression times of sensory block and 1st analgesic requirement in Group II were significantly longer than in Group I. Incidence of paresthesia due to spinal needle (3.3% versus 20% in Groups I and II, respectively) and number of attempts to perform CSE (26.7% versus 60% in Groups I and II, respectively) were significantly higher in Group II. Apgar scores were similar in both groups. CONCLUSION: Performing CSE in the sitting position would be safer and easier because higher and earlier onset of sensory block, and a greater number attempts at epidural insertion and paresthesia develop to spinal needle insertion in the right lateral position. PMID- 27366385 TI - Effects of Metastasis on Pain Treatment in Patients with Cancer-Related Pain: A Retrospective Study. AB - OBJECTIVE: The goal of this study was to investigate the effect of the presence of metastases on pain treatment in patients with cancer-related pain. METHODS: Of the 1736 patients who were treated in Firat University, Faculty of Medicine, Department of Anaesthesiology and Reanimation, Algology Section, for cancer related pain between January 1997 and December 2010, 1467 with complete medical records were evaluated. Patients were grouped as having no metastasis (Group I), a single organ metastasis (Group II), or multiple organ metastasis (Group III). RESULTS: There was no difference between the groups with regard to age. Visual Analog Pain (VAS) scores at admission were higher in Group III compared to the other groups, and significantly higher in Group I than in Group II. Analgesic ladder treatment was given to 85.5% of patients, and 14.5% were treated using additional minimally invasive analgesic intervention (MIAI) methods. In Group II and Group III, the rates of treatment in Step I and II were lower compared to Group I, while the rates of treatment in Step III were higher. Implementation of MIAI was higher in Group III than in the other groups, and higher in Group II than in Group I. CONCLUSION: The presence of metastases causes more severe pain, which becomes more difficult to treat, and increases the analgesia step and the consumption of opioids in patients with cancer-related pain. PMID- 27366386 TI - Ultrasound-Guided Bilateral Greater Occipital Nerve Block for the Treatment of Postdural Puncture Headache. AB - Treatment of postdural puncture headaches involves oral or intravenous (IV) fluid or caffeine-containing analgesics, micro-catheterization of spinal space, epidural administration of blood obtained from the patient, or epidural blood patch and fiberoptic imaging-guided epidural interventional techniques. Epidural blood patch is, to date, the most effective treatment, but it is an invasive procedure that may result in serious complications. Spinal anaesthesia was planned for a 22 year old male patient diagnosed with inguinal hernia and for a 42 year old female patient diagnosed with venous stasis. On the first post operative day, the patients with a postdural puncture headache received conservative medical treatment. As medical treatment was ineffective, they received ultrasound-guided greater bilateral occipital nerve block. In this case report, the effect of the ultrasound-guided bilateral greater occipital nerve block on postdural puncture headache is discussed. PMID- 27366387 TI - Total Spinal Block after Thoracic Paravertebral Block. AB - Thoracic paravertebral block (TPVB) can be performed with or without general anaesthesia for various surgical procedures. TPVB is a popular anaesthetic technique due to its low side effect profile and high analgesic potency. We used 20 mL of 0.5% levobupivacaine for a single injection of unilateral TPVB at the T7 level with neurostimulator in a 63 year old patient with co-morbid disease who underwent cholecystectomy. Following the application patient lost consciousness, and was intubated. Haemodynamic instability was normalised with rapid volume replacement and vasopressors. Anaesthetic drugs were stopped at the end of the surgery and muscle relaxant was antagonised. Return of mucle strenght was shown with neuromuscular block monitoring. Approximately three hours after TPVB, spontaneous breathing started and consciousness returned. A total spinal block is a rare and life-threatening complication. A total spinal block is a complication of spinal anaesthesia, and it can also occur after peripheral blocks. Clinical presentation is characterised by hypotension, bradicardia, apnea, and cardiac arrest. An early diagnosis and appropriate treatment is life saving. In this case report, we want to present total spinal block after TPVB. PMID- 27366388 TI - Diphenylhydantoin Induced DRESS Syndrome: A Case Report. AB - Drug Rash with Eosinophilia and Systemic Symptoms" (DRESS) syndrome is a severe adverse drug reaction. The drugs most often implicated are anti-convulsants, bupropion, sulfonamides, sulfasalazine, allopurinol, minocycline, abacavir and neviparine. There are also immune and infectious causes that can lead to DRESS syndrome. A 70-year-old female patient had undergone endovascular coil embolization for intracranial aneurysm and experienced a generalised seizure postoperatively. She had been given diphenylhidantoin (DPH). Six days after DPH therapy, the patient had complained of widespread skin rash. Although DPH was replaced with levetiracetam afterwards, the skin rash deteriorated, causing facial oedema and swelling of the tongue. She had severe facial oedema with swelling of the tongue, causing disturbance of breathing. On the second day in the critical care unit, the patient's breathing deteriorated, leading successively to intubation and mechanical ventilation. The patient's rash was still persistent and the results of a punch biopsy taken from the lesions revealed superficial perivascular dermatitis involving spongiotic eosinophils compatible with spongiotic drug eruption. As a result, it is important to realise that medications we use can be the cause of a range of reactions ranging from simple rash to life threatening syndromes. PMID- 27366389 TI - Posterior Reversible Encephalopathy Syndrome in an Eclamptic Patient After Cardiac Arrest; Case Report and Literature Review. AB - Posterior reversible encephalopathy (PRES) is a disorder characterized by hypertension, headache, seizures and visual impairment. Causes of PRES include; severe hypertension, pre-eclampsia or eclampsia, sepsis, history of renal and autoimmune diseases and use of immunosuppressive or cytotoxic agents. Diagnosis of the syndrome can be difficult. For this reason clinical and radiological findings should be evaluated together. In this report, a 19-year old, 32 week pregnant eclamptic woman, who had been diagnosed with PRES, is presented with a discussion of the relevant literature. PMID- 27366390 TI - Aortic and Venous Cannulation in Coronary Surgery. PMID- 27366391 TI - Complication of Interscalene Block: "Subdural Block". PMID- 27366393 TI - Survey on Postoperative Hypothermia Incidence In Operating Theatres of Kocaeli University. AB - OBJECTIVE: Hypothermia is a common problem in anaesthetized patients and an important risk factor for mortality and morbidity. Our aim was to identify the incidence of hypothermia in our operating theatres. We also aimed to find the circumstances to which hypothermia could be related. METHODS: After obtaining the ethics committee approval and informed patient consent, patients with operation times longer than 30 minutes were included into the study for a one month period. Demographical data of the patients, type and duration of surgeries, temperatures measured pre and postoperatively from the tympanic membrane with an infrared thermometer were recorded. Temperatures below 35 degrees C were accepted as hypothermia. RESULTS: A total number of 564 patients were enrolled to the study (305 women and 259 men). The ages of patients varied from 1 month to 84 years (mean 38.5+/-20.7). Hypothermia incidence was calculated as 45.7%. When the factors related to hypothermia were considered, age, type and duration of surgery and amount of fluids administered were found to be significant contributors to the development of hypothermia (p<0.05). CONCLUSION: Postoperative hypothermia is a common problem in our clinic. Therefore, we suggest that temperature monitoring and patient warming should be a routine procedure during anaesthesia management. PMID- 27366394 TI - Effect of Anaesthesia Methods for Regaining Daily Life Activities in Cesarean Patients. AB - OBJECTIVE: Postpartum period is physically, socially and emotionally a difficult time for the parents and the baby to become a family. We tried to investigate how the anaesthesia method affects patients who underwent cesarean delivery, as a factor which also affects this period. METHODS: Two hundred and six parturients, who underwent elective cesarean delivery in Celal Bayar University Hafsa Sultan Hospital were recruited for our study. After demographic data and anaesthesia methods were noted, an EQ-5D health survey and Katz ADL scale were evaluated face to face 24 hours postoperatively, and by telephone on the 5th postoperative day. RESULTS: The percentage of patients who had general anaesthesia was 35.2% (n=71), while 19.8% (n=40) had epidural anaesthesia and 45% (n=91) had spinal anaesthesia. Among -these three methods, the EQ-5D health survey revealed that the outcome at postoperative 24 hours was best in epidural anaesthesia and that general anaesthesia outcome was the worst (p=0.007). The Katz ADL scale at postoperative 24. hours showed that epidural anaesthesia was better than the other methods for regaining daily life activities (p<0.05). CONCLUSION: Our study showed that epidural anaesthesia had the most effective role among the methods in regaining daily life activities after elective cesarean delivery, which was demonstrated using the EQ-5D health survey and Katz ADL scale. PMID- 27366392 TI - Perioperative Haemodynamic Optimisation. AB - During the latest years, a number of studies have confirmed the benefits of perioperative haemodynamic optimisation on surgical mortality and postoperative complication rate. This process requires the use of advanced haemodynamic monitoring with the purpose of guiding therapies to reach predefined goals. This review aim to present recent evidence on perioperative goal directed therapy (GDT), with an emphasis in some aspects that may merit further investigation. In order to maximise the benefits on outcomes, GDT must be implemented as early as possible; intravascular volume optimisation should be in accordance with the response of the preload-reserve, goals should be individualised and adequacy of the intervention must be also assessed; non-invasive or minimally invasive monitoring should be used and, finally, side effects of every therapy should be taken into account in order to avoid undesired complications. New drugs and technologies, particularly those exploring the venous side of the circulation, may improve in the future the effectiveness and facilitate the implementation of this group of therapeutic interventions. PMID- 27366395 TI - Post-Laparoscopic Cholecystectomy Pain: Effects of Preincisional Infiltration and Intraperitoneal Levobupivacaine 0.25% on Pain Control-a Randomized Prospective Double-Blinded Placebo-Controlled Trial. AB - OBJECTIVE: The aim of this study was to compare the postoperative analgesic efficacy of preincisional and intraperitoneal levobupivacaine or normal saline in patients undergoing laparoscopic cholecystectomy. METHODS: Sixty patients who participated in the study were randomly divided into 3 groups. Group 1 received intraperitoneal levobupivacaine (0.25% 40 mL) immediately after the pneumoperitoneum. Group 2 received periportal levobupivacaine (0.25% 5 mL in each trochar incision area) before incision and intraperitoneal levobupivacaine (0.25% 40 mL) immediately after the pneumoperitoneum. Group 3 received for periportal and intraperitoneal instillation of normal saline. The visual analog scale (VAS) at 0, 1, 2, 4, 8, 12 and 24 hours for both shoulder and abdominal pain were recorded. Analgesia requirements and incidence of nausea and vomiting were also recorded. RESULTS: There were no difference between the groups for demographic data. The pain scores were lower in Groups 1 and 2 than Group 3 (control) during rest, cough and movement (p<0.05). Rescue analgesic treatment was significantly lower in patients of Group 2 (15%) as compared with that of Groups 1 (35%) and 3 (90%) (p<0.05). The incidence of shoulder pain was significantly lower in Group 2 (25%) and Group 1 (20%) than in any of the control group patients (p<0.05). CONCLUSION: The results indicated that 0.25% levobupivacaine was effective in preventing pain and the need for postoperative analgesic when intraperitoneal instillation or preincisional local infiltration in combination with intraperitoneal instillation. However, levobupivacaine for preincisional local infiltration in combination with intraperitoneal instillation is the better choice because of its higher efficacy. PMID- 27366396 TI - Effects of Esmolol on the Prevention of Haemodynamic Responses to Tracheal Extubation after Craniotomy Operations. AB - OBJECTIVE: The aim of this study was to evaluate the effects of esmolol infusion on the prevention of haemodynamic responses to tracheal extubation in patients undergoing elective craniotomy. METHODS: With approval from the Medical School Ethics Committee at Marmara University and the patients' written consent, 30 patients between 20-65 years of age undergoing elective craniotomy were randomly placed in either the Group Esmolol (n=15) or the Group Control (n=15). Anaesthesia was induced with 5-7 mg kg(-1) thiopental sodium, 1 MUg kg(-1) remifentanil, and 0.1 mg kg(-1) vecuronium bromide iv, and was maintained with 1 MAC sevoflurane in oxygen-air mixture (50:50) and 0.25 MUg kg(-1) min(-1) remifentanil infusion. At the end of the operation, patients inhaled 100% oxygen after the discontinuation of the anaesthetic agents. For Group Esmolol, 5 min before extubation 2 mg kg(-1) esmolol in 50 mL was infused over 10 min (0.2 MUg kg(-1) min(-1)), while for Group Control, 50 mL saline was infused over 10 min. The quality of extubation was evaluated with a 5 point scale, recording heat rate, systolic, diastolic, and mean arterial pressures before infusion, 1 min after infusion, during extubation, and at 1, 3, 5, and 10 min after extubation. RESULTS: In the esmolol group, systolic, diastolic, and mean arterial pressures, as well as heart rate, decreased significantly after esmolol infusion and were significantly lower than in the control group after extubation (p<0.05). The ratio of patients with an extubation score of one was significantly higher in the esmolol group than in the control group (p<0.05). CONCLUSION: We concluded that 2 mg kg(-1) esmolol infusion before extubation can prevent hypertension and tachycardia caused by extubation in patients undergoing elective craniotomy. PMID- 27366397 TI - The Comparison of Automatic Tube Compensation (ATC) and T-piece During Weaning. AB - OBJECTIVE: Automatic Tube Compensation (ATC) is a newly developed mechanical ventilatory support method. The aim of this study was to compare the ATC and the T-piece as a weaning method. METHODS: Patients who were treated in ICU with mechanical ventilation for longer than 24 hours were included in this prospective clinical study. Fifty patients were divided into two groups for weaning, ATC or T piece group. Patients tolerating 30 minutes spontaneous breathing trial underwent immediate extubation. The following parameters were recorded just before the spontaneous breathing trial and every 5 minutes during the 30 minute period; PEEP, Pplt, Pmean, FiO2, heart rate, systolic blood pressure, diastolic blood pressure, respiratory rate, SaO2, ETCO2. The primary outcome of the study was successful extubation defined as the ability to maintain spontaneous breathing for 48 hours after extubation. RESULTS: The mean duration of weaning were 4.96 days and 7.42 days in the ATC and T-piece groups, respectively (p value 0.022). There were no significant differences between the groups with respect to the hemodynamic parameters, mechanical ventilation and gas exchange parameters. CONCLUSION: In terms of success for weaning, there was no superiority between the ATC and the T-Piece methods for spontaneous breathing and it was concluded that each of the methods can be used for weaning. The ATC group were compared in terms of successful weaning period but have shown no significant periods of time were found to be lower. PMID- 27366398 TI - Wernicke's Encephalopathy After Longterm Feeding with Parenteral Nutrition. AB - Wernicke's encephalopathy occurs due to thiamine (vitamin B1) deficiency which is characterized by occulomotor dysfunction, confusion and ataxia. Although it is most common with alcoholism, can also be seen due to hyperemesis caused by chemotherapy, Crohn's disease, gastrointestinal system surgery, AIDS, bariatric surgery and longterm feeding with parenteral nutrition. In this case, a 51-year old woman who was treated with longterm total parenteral nutrition due to hyperemesis and had the diagnosis of Wernicke's encephalopathy after admission to the intensive care unit is presented. PMID- 27366399 TI - Guillain-Barre Syndrome and Human Immunodeficiency Virus. AB - Guillain-Barre syndrome (GBS) is an acute disease characterised by symmetrical muscle weakness, loss of sensation and reflex. There is usually a viral infection at the beginning of the disease. Here, we report a GBS case which did not respond to any treatment strategy at first and was diagnosed as Human Immunodeficiency Virus positive (HIV+) during the search for the aetiology. A 32-year-old male patient who presented to a medical centre with symptoms of gait disturbance and arm and leg numbness was found to have albuminocytologic dissociation upon cerebrospinal fluid examination. After the diagnosis of GBS, immunoglobulin G (IVIG) therapy (400 mg kg(-1) day(-1) 5 days) was started as a standard therapy. This therapy was repeated due to a lack of improvement of symptoms. During this therapy, the patient was sent to our clinic with symptoms of respiratory failure and tetraplegia. He was conscious, cooperative, haemodynamically stable and his arterial blood gas analyses were: pH: 7.28, PaO2: 74.4 mmHg, PCO2: 63.8 mmHg. He was intubated, mechanically ventilated and underwent plasmapheresis. After the investigation of aetiology, HIV(+), CD4/CD8: 0.17, absolute CD4: 71 cells mL(-1) were detected and antiretroviral therapy was started. The patient died from multiple organ failure due to sepsis on day 35. In conclusion, HIV infection should be kept in mind in GBS patients, especially those not responding to routine treatment. As a result, not only could the patient receive early and adequate treatment, but also HIV infection transmission would be avoided. PMID- 27366400 TI - Anaesthetic Management of a Child with Limb-Girdle Muscular Dystrophy. AB - Limb-girdle muscular dystrophies are a group of disorders with wide genetic and clinical heterogeneity. These disorders may lead to an increase in life threatening complications related to surgery and anaesthesia. In this case, the anaesthetic management of a child with limb-girdle muscular dystrophy is presented. PMID- 27366401 TI - Does Low Dose Lidocaine Cause Convulsions? AB - In anaesthesiology practice, lidocaine is commonly used for local and regional anaesthesia as well as to decrease haemodynamic response to intubation. Lidocain usage within the safe dose range is suggested and in case of overdose; systemic intoxication, central nervous system and cardiovascular system toxicity may occur. Convulsions, cardiac collapse and coma are reported in relation to overdoses of lidocain. In this report; the convulsion event, which occurred after injection of intravenous 1 mg kg(-1) 1% lidocaine to inhibit intubation-related hemodynamic side effects in patients scheduled for vitrectomy under general anaesthesia due to retinal detachment, is presented. PMID- 27366402 TI - Comparison Parasacral and Posterior Sciatic Nerve Blocks Combined Anterior Lumbar Plexus Block. PMID- 27366403 TI - Factors Affecting Tissue Oxygenation in Erythrocyte Transfusions. AB - Red blood cell transfusions are used to increase the oxygen-carrying capacity of blood in anemic states. But, because of the changes during storage of blood components and the specifics of preparation, erythrocytes may have controversial effects on tissue oxygenation and microcirculation. Also, the patient situation may play a role in the differing responses in oxygenation and microcirculation. In this review, the studies concerning the effects of banked blood and patient characteristics on microcirculation and tissue oxygenation are summarized. PMID- 27366404 TI - The Effect of BIS Usage on Anaesthetic Agent Consumption, Haemodynamics and Recovery Time in Supratentorial Mass Surgery. AB - OBJECTIVE: In this study, we aimed to compare Bispectral Index (BIS) monitoring with the conventional anaesthesia approach based on haemodynamic changes in terms of anaesthetic agent consumption, haemodynamic recordings, recovery time and cost. METHODS: This study was performed in 82 patients, aged 20 to 60 years, who were operated for supratentorial mass and were graded ASA I or II. Cases were randomly divided into two equal groups. In the standard control group haemodynamic parameters were used to determine depth of anaesthesia and in the BIS group, BIS monitoring was applied. In the BIS group the BIS values were kept between 40 and 60; in the control group haemodynamic changes within the range of +/-20% of initial values were controlled using appropriate anaesthetic practice. Haemodynamic parameters, awakening conditions and drug usage were recorded. RESULTS: The difference between the two groups in terms of timing of eye opening and initial spontaneous breath was not statistically significant. The 'Aldrete' score at the 20(th) postoperative minute for the BIS group was significantly higher than the score calculated for the control group (p<0.05). Rocuronium consumption (mg kg(-1) hr(-1)) was significantly lower in the BIS group than the control group (p<0.05). Although a statistically significant difference (p<0.05) was found between the two groups in terms of initial heart rate and SpO2 values, there was no clinically significant difference in other haemodynamic parameters. CONCLUSION: Although using BIS monitoring to evaluate depth of anaesthesia does not bring much benefit versus the use of haemodynamic parameters, it may be beneficial for selected surgeries such as awake craniotomy, for patients with a history of awareness and in haemodynamically unstable patients. PMID- 27366405 TI - The Effect of Flurbiprofen on Postoperative Sore Throat and Hoarseness After LMA ProSeal Insertion: A Randomised, Clinical Trial. AB - OBJECTIVE: We hypothesized that flurbiprofen lozenges reduce the ProSeal laryngeal mask airway (LMA) related symptoms of Post Operative Sore Throat (POST), hoarseness and dysphagia compared to placebo lozenges. METHODS: Eighty American Society of Anesthesiologists (ASA) I-II patients undergoing general anaesthesia with LMA were included in this prospective, randomized, placebo controlled clinical and single centre (university hospital) study. Group F received an 8.75 mg flurbiprofen lozenge (Strefen((r))) and Group P received a placebo lozenge 45 minutes before the induction of anaesthesia. Postoperative sore throat, hoarseness and dysphagia were evaluated 30 minutes after removal of the LMA in the recovery room and then at 4, 12 and 24 h after surgery using a 4 point scale. Data were analysed using Student's t test, and Fisher's exact and Mann-Whitney U tests. A p value of <0.05 was considered statistically significant. RESULTS: The 8.75 mg flurbiprofen lozenges reduced the severity of early (30 mins) POST and dysphagia. The severity of dysphagia at 4 h and hoarseness at 12 h were also significantly reduced in Group F. There were no significant differences betweeen the groups regarding incidence of sore throat, dysphagia and hoarseness throughout the study period. CONCLUSION: Preoperative flurbiprofen lozenges reduce the severity of early postoperative sore throat and dysphagia. PMID- 27366406 TI - Anaesthesia Techniques for Caesarean Operations: Retrospective Analysis of Last Decade. AB - OBJECTIVE: The technique of anaesthesia in caesarean sections is selected according to the patient's clinical presentation, experience of the anaesthesist and the patient's wishes. The purpose of this study was to evaluate the anaesthesia methods employed in our clinic in the last decade (2003-2012). METHODS: Records of caesarean operations performed between 2003-2012 in the Anaesthesia department of Ataturk University Medical Faculty and stored in the hospital computer system were examined. The annual distribution of methods of anaesthesia in operations was analysed. RESULTS: During 2003-2012, 9049 caesarean operations were performed in our clinic. General anaesthesia was used in 45% of operations and regional anaesthesia in 54%. Whereas the rate of regional anaesthesia in 2003 was 34%, this increased to 69% in 2012. The most commonly used method of regional anaesthesia was spinal anaesthesia (34%) in 2003, and spinal anaesthesia (41%) and combined spinal-epidural anaesthesia (27%) in 2012. CONCLUSION: The most commonly used anaesthesia technique for caesarean operations in our clinic between 2003-2012 was spinal anaesthesia. The most widely used regional anaesthetic method in our clinic was spinal anaesthesia. A significant increase in the use of the combined spinal-epidural anaesthetic technique occurred in the last two years of the study period. PMID- 27366407 TI - Retrospective Evaluation of Anaesthesia Techniques for Hip Replacement Operations. AB - OBJECTIVE: In this retrospective study, we evaluated the demographic characteristics of patients that underwent hip replacement surgery in our orthopedic clinic. Associated diseases, preoperative laboratory findings, intraoperative findings, and the effect of admission or refusal to the intensive care unit on postoperative mortality and morbidity were recorded. Furthermore, we tried to identify surgical and anaesthetic methods applied, intraoperative hemodynamic changes, length of stay in the post-anaesthesia care unit, and postoperative complications. METHODS: Demographic characteristics, co morbidities, preoperative laboratory findings, intraoperative findings, and admission or refusal to the intensive care unit of patients who underwent hip replacement surgery between January 2008-December 2010 were enrolled. RESULTS: Out of 500 patients, 33.4% (n=164) were operated under general anaesthesia, 34% (n=170) under combined spinal-epidural anaesthesia, 22.2% (n=111) under spinal anaesthesia, 6.4% (n=32) under combined lomber plexus block and sciatic nerve block, and 4% (n=20) under epidural anaesthesia. Mean hospital stay was 7 days in the general anaesthesia group and 5 days in the regional anaesthesia group. CONCLUSION: American Society of Anesthesiologists (ASA) scores and incidence of co-morbidities were higher in the partial hip replacement group. Admission to the intensive care unit was lower in the total hip replacement group. Hospital stay was shorter in the partial hip replacement group. Mortality rates on the 7(th) and 30(th) days were higher in the partial hip replacement group. PMID- 27366408 TI - Evaluating the Readibility of Informed Consent Forms Available Before Anaesthesia: A Comparative Study. AB - OBJECTIVE: Informed consent forms that are used prior to administering anaesthesia inform patients before any proposed surgical procedure or treatment. They should provide patients with sufficient information about the operation and treatment. Readibility refers to whether it is easy or hard for a reader to read and understand an available text, and this is evaluated via various formulas. The aim of this study was to evaluate the readability of different informed consent forms commonly used in the anaesthesiology departments of different hospitals in our country using different readability formulas. METHODS: After obtaining ethics committee approval, the readability of different consent forms used in the anaesthesiology departments of university hospitals (n=15), Ministry of Health (MOH) education and research hospitals (n=15), and public hospitals (n=15) was analysed. Each consent form was displayed electronically in "Microsoft Word" and the number of words contained was counted automatically. The first 100 words on the first page of the forms were evaluated using the Gunning Fog, Flesch-Kincaid and Atesman readability formulations. The rate of medical terms detected within these 100 words was determined as a percentage (%). RESULTS: Different consent forms obtained from 45 anaesthesia departments were assessed using various readability formulas. According to the Gunning Fog index, the readability of the consent forms obtained from MOH education and research and public hospitals was relatively low. The Flesch-Kincaid index measured very low levels of readability in all institutions. The Atesman index displayed very low readability levels for the consent forms used in university hospitals, and low levels in other institutions. CONCLUSION: We conclude that the readability of the anaesthesia informed consent forms is low. The level of education in our country should be considered in the preparation of anaesthesia consent forms. We believe that physicians should pay more attention to this medical and legal issue. PMID- 27366409 TI - Anaesthetic Management in Electroconvulsive Therapy During Early Pregnancy. AB - The management of major psychiatric conditions during pregnancy is exceptionally difficult. Pharmacoresistant, life-threatening and severe symptoms such as catatonia and suicidal behavior affect the health and safety of both mother and child. In such cases, electroconvulsive therapy (ECT) may be considered as an alternative to pharmacologic treatment. In this report, we aimed to present anaesthetic management of a patient, who was 13 weeks pregnant and needed ECT due to major depression. PMID- 27366410 TI - Combined Spinal Epidural Anaesthesia for Caesarean Section and Hysterectomy in a Parturient with Placenta Accreta. AB - Placenta accreta complicates the anaesthetic and surgical approach in caesarean section. In this report, a parturient with placenta accreta and multiple drug allergies who was managed using combined spinal epidural anaesthesia for caesarean hysterectomy is discussed. PMID- 27366411 TI - Unilateral Sixth Cranial Nerve Palsy Following C/S as a Complication of Spinal Anaesthesia. AB - Cranial nerve palsy (CNP) is a rare complication following lumbar puncture, which is a common procedure used most often for diagnostic and anaesthetic purposes. The sixth cranial (abducens) nerve is the most commonly affected cranial nerve. We report a case of unilateral sixth nerve palsy after spinal anaesthesia that improved immediately after an epidural blood patch (EBP). PMID- 27366412 TI - Acute Phase Reaction after Femur Fracture in a Child with Griscelli Syndrome. AB - Griscelli syndrome (GS) is an autosomal recessive disorder that is characterized by partial albinism of the skin and hair shaft. Prompt and early diagnosis is a crucial step for the follow up and management of GS, which would otherwise dramatically decrease the life expectancy of the patients. This case report presents the clinical course of a femoral fracture treated with closed reduction and pelvic-pedal cast, and progression of acute phase reaction during the follow up period. PMID- 27366413 TI - Difficult Laryngeal Mask Airway Placement. PMID- 27366414 TI - Mallampati 'Zero' Airway: Extremely Easy or Not? PMID- 27366415 TI - Readmission To Intensive Care Unit After Coronary Bypass Operations in the Short Term. AB - OBJECTIVE: Intensive care unit (ICU) readmissions after coronary bypass (CABG) operations occur in a significant number of patients, and the prognosis is poor. We analyzed the risk factors for ICU readmissions after CABG operations. METHODS: We retrospectively analyzed the prospectively collected data of 679 coronary bypass patients operated in a single institution in order to evaluate the risk factors for readmittance to the ICU with logistic regression analysis. The outcome results of patients readmitted to the ICU (Group R) and others (Group N) were compared. RESULTS: Thirty-six (5.3%) patients were readmitted to the ICU. Postoperative in-hospital mortality and pulmonary and neurologic morbidity occurred in 43 (6.3%), 135 (19.9%), and 46 (6.8%) patients, respectively. The comparison of groups showed that mortality and morbidity were significantly higher in Group R compared to Group N (mortality 16.7% vs. 5.9, p=0.029; pulmonary morbidity 66.7% vs. 17.3%, p=0.0001; neurologic morbidity 38.9% vs. 5.0%, p=0.0001). Features associated with readmission included presence of left ventricular dysfunction preoperatively[odds ratio (OR)=4.1; 95% confidence interval (CI)=1.4-12.5; p=0.013], advanced NYHA Class (OR=5.3; 95% CI=1.3-21.7; p=0.022), pulmonary complications (OR=7.3; 95% CI=2.1-25.5; p=0.002), and neurologic complications (OR=4.6; 95% CI=1.3-16.7; p=0.021). CONCLUSION: Patients readmitted to the ICU postoperatively have higher rates of mortality and pulmonary and neurologic morbidity after coronary bypass operations. Left ventricular dysfunction, advanced NYHA class, and postoperative pulmonary and neurologic complications are significant risk factors for readmission to the ICU. PMID- 27366416 TI - The Comparison of Pressure (PSV) and Volume Support Ventilation (VSV) as a 'Weaning' Mode. AB - OBJECTIVE: The purpose of our study is to compare two different ventilation modes pressure support ventilation (PSV) and volume support ventilation (VSV)-as the means of weaning. METHODS: Sixty patients were enrolled in our study. Patients were randomized in to two groups. For the PSV group, FiO2 and airway pressure values were adjusted in order to sustain PaCO2: 35-45 mm Hg, pH>7.32, 6-8 mL kg( 1) TV (tidal volume), and saturation >92%. For the VSV group, FiO2, TV, respiration frequency (f), and peak pressure were adjusted to obtain PaCO2: 35-45 mm Hg, pH>7.32, 6-8 mL kg(-1) TV, saturation >92%, and PO2>60 mm Hg. Every morning, spontaneous breathing was tried in those patients. The patients were extubated after 2 hours of T-piece breathing. The patients who failed spontaneous respiration with the T-piece were returned to mechanical ventilation. Assisted ventilation time (ART), mechanical ventilation time (MRT), total T-piece time (TTT), total weaning time (TWT), and sedation need (SN) values were recorded. "T test" and "Chi-square" methods were used for statistical analysis. RESULTS: In our study, the mean ART was 82.60 hours for the PSV group and 56.03 hours for the VSV group (p<0.041). TWT was 93.30 hours for the PSV group and 56.03 hours for the VSV group (p<0.035). The mean TTT was 7.67 hours for the PSV group and 3.83 hours for the VSV group (p<0.007). Nineteen patients in the PSV group and 9 patients in the VSV group required sedation during the weaning process (p<0.01). CONCLUSION: In the weaning period, VSV seems to be more advantageous than PSV. PMID- 27366417 TI - Factors Influencing the Preference of Regional Anaesthesia in the Obstetric Population: A Survey Study. AB - OBJECTIVE: Most patients in Turkey still prefer general anaesthesia (GA) and are somehow afraid of regional blocks. Receiving adequate information is likely to increase patients' awareness about regional anaesthesia (RA). We aimed to determine the current preferences of parturients, the reasons for refusal of RA techniques, and how detailed information about the type of anaesthesia affect a patient's preference for anaesthesia among obstetric cases. METHODS: One hundred fifty patients, scheduled for elective caesarean section (C/S), were surveyed before and after the C/S. The survey included three parts: the first part involved demographic features, anaesthesia preferences, prior opinions and experiences related to RA, and assessment of preoperative fears and reasons, and the second part involved persuasion of patients after reading the information sheet about RA. The final part was composed of postoperative satisfaction and complications related to the RA or GA depending on the patients' preferences. Complications were recorded on the anaesthesia chart. RESULTS: Of all patients, 42.7% (n=64) approved and 48% (n=72) refused RA at the first preoperative anaesthesia visit. The remaining patients (n=14) had no idea of which anaesthesia type to choose. After being informed about RA in detail, 48 (66.6%) of the patients who previously refused RA and all patients who had no idea approved the procedure, and all of them were satisfied with the anaesthesia following the procedure. CONCLUSION: Our study revealed exactly that particularly obstetric anaesthetists should inform their patients about the advantages and disadvantages of all alternative types of anaesthesia. Effective and correct information is the major point. PMID- 27366418 TI - Comparison of the C-MAC D-Blade, Conventional C-MAC, and Macintosh Laryngoscopes in Simulated Easy and Difficult Airways. AB - OBJECTIVE: Recently, to further enhance the potential in the management of difficult airways, the highly angulated D-Blade was added to the C-MAC system. The purpose of this study was to investigate the laryngoscopic view and intubation parameters using the new C-MAC D-Blade in comparison to the conventional C-MAC video laryngoscope and Macintosh direct laryngoscope in simulated easy and difficult airways. METHODS: We recruited 26 experienced anaesthesia providers into a randomized trial. Each performed tracheal intubation of a Laerdal SimMan((r)) manikin with each laryngoscope in the following laryngoscopy scenarios: (1) normal airway, (2) cervical spine immobilization, and (3) tongue edema. The intubation times, success rates, number of intubation attempts, laryngoscopic views, and severity of dental compression were recorded. RESULTS: In all scenarios, video laryngoscopes provided better laryngeal exposure than the ML and appeared to produce less dental pressure. In the cervical spine immobilization scenario, D-Blade caused less dental pressure and showed better Cormack-Lehane (CL) classes than the other devices (p<0.001). There were no differences between video laryngoscopes in success of tracheal intubation (p>0.05). The CMAC provided the most rapid intubation. The rate of failure was 19% with ML. In the tongue edema scenario, the CMAC provided the most rapid and successful intubation (p<0.001). There were no differences between video laryngoscopes in laryngoscopic views according to CL classification and dental pressure (p>0.05). The rate of failure was 46% with the ML and 7% with the D Blade. CONCLUSION: The CMAC D-Blade caused less dental pressure than the conventional C-MAC and ML in the cervical immobilization scenario. The conventional CMAC performed better than the D-Blade and ML in the tongue edema scenario. These two video laryngoscopes may complement each other in various difficult airway situations. PMID- 27366420 TI - The Attitudes and Behaviors of Anaesthesiology and Reanimation Specialists in Anaesthesia Care Applications Outside the Operating Room in Turkey: A Survey Study. AB - OBJECTIVE: We aimed to investigate the attitudes and behaviors of anaesthesiologists in "non-operating room anaesthesia" applications, which can be described as anaesthesia applications performed outside the operating room, and their reflection on practice all over Turkey. METHODS: Our study was conducted between November 5, 2012 and January 7, 2013 with the approval of the Research Ethics Board. Survey data were obtained through distributing printed questionnaires to be completed either by hand or via the web. The questionnaire consisted of 38 questions. The data obtained were analyzed with the Statistical Package for Social Sciences (SPSS) program. RESULTS: A total of 500 anaesthesiologists replied to our survey; 93% of anaesthesia specialists reported that there was a request that the anaesthesia and anaesthesia outside the operating room was given in their institution. Among anaesthesiologists, 56% reported that there were other sections that can provide sedation other than the anaesthesiology department in their institutions. Anaesthesia care team members; equipment; anaesthetic techniques; monitoring methods; and hypnotic, analgesic, and antagonist agents had statistically significant differences according to the participants' institutions. Equipment used in the anaesthesia practice outside the operating room, anaesthesia, and monitoring methods had statistically significant differences according to geographical distribution (p<0.05). CONCLUSION: Outside the operating room, anaesthesia practices and security measures are compliant with the standards set by the guidelines, the key to the prevention of complications. In our study, the current status of anaesthetic procedures outside the operating room in our country have been analyzed. PMID- 27366419 TI - Spinal Anaesthesia and Perioperative Anxiety. AB - OBJECTIVE: Anxiety is a pathological condition with a feeling of fear accompanied by somatic symptoms due to hyperactivity of the autonomic nervous system. In this study, we aimed to compare perioperative anxiety status and the effects of age, gender, educational status, and The American Society of Anesthesiologists physical status classification (ASA) score on perioperative anxiety in patients undergoing elective surgery under spinal anaesthesia. METHODS: After IRB approval and signed informed consent, 100 healthy patients undergoing elective surgery under spinal anaesthesia were enrolled. The demographic data of patients and ASA scores were recorded. After spinal anaesthesia, State Trait Anxiety Inventory (STAI) and anxiety levels were measured. RESULTS: The mean anxiety score in patients undergoing surgery under spinal anaesthesia indicate the presence of an intermediate level of anxiety (44.58+/-19.06). A statistically significant positive correlation was found between anxiety scores and age of patients with increased age (p<0.01). Statistically significant differences were found between anxiety scores of patients according to gender, and women's anxiety scores were found to be significantly higher than in men (p<0.05). Anxiety scores did not differ significantly between education levels. A statistically significant difference was found between anxiety scores regarding ASA scores (p<0.05). Evaluation of patients revealed that the anxiety score of patients with ASA score 1 was significantly higher than the anxiety score of patients with ASA score 2. There was no significant difference between anxiety score of patients with ASA scores 2 and 3. CONCLUSION: There is a mid-level anxiety, associated more with advanced age, female gender, and low ASA score, in patients undergoing elective surgery under spinal anaesthesia. PMID- 27366421 TI - Management of Difficult Airway in a Failed Intubation with Videolaryngoscopy in an Infant Patient. AB - The videolaryngoscope is a useful alternative airway device for anaesthesia management of difficult airways. However videolaryngoscope intubation may fail due to lack of experience, incorrect application, inappropriate stylet, prior traumatic attempts, restricted cervical movement and limited oropharyngeal airspace. Using a stylet and correctly shaped endotracheal tube is important to facilitate tracheal intubation with the videolaryngoscope, especially in paediatric patients. However, anatomical difficulty in the placement of the laryngoscope blade, association with facial deformities such as micrognathia, having a short neck, cleft palate and being younger than 1 year increase the likelihood of a difficult airway. In this report, we present our approach to difficult airway management in a failed intubation with a videolaryngoscope in an infant undergoing cleft palate surgery. PMID- 27366422 TI - Anaesthetic Management of a Patient with Hereditary Angioedema. AB - Hereditary angioedema (HAE) is a rare autosomal dominant disorder caused by reduced activity of the C1 esterase inhibitor. Clinically, angioedema most often involves the upper extremities, face, neck and larynx. The most common cause of death is asphyxia related to laryngeal oedema. Attacks are triggered by many factors such as trauma, stress, infections and hormonal fluctuations. C1 esterase inhibitor concentrates, fresh frozen plasma (FFP), androgen steroids, quinine pathway inhibitors and antifibrinolytics can be used as treatment. In this case report, the anaesthetic management of a patient with hereditary angioedema undergoing laminectomy surgery is reported. PMID- 27366423 TI - Surgical Excision of Postintubation Granuloma Under Jet Ventilation. AB - Following the use of an endotracheal or tracheostomy tube, circumferential lesions, stenosis, or granulomatous lesions at the cuff level or tip of the tube may be observed on the tracheal wall. This injury mainly occurs due to excessive pressure of the cuff on the tracheal wall and may be prevented by a high-volume, low-pressure cuff and a carefully monitored tracheostomy tube. Although there is an overall improvement in the design of high-volume cuffs, hyperinflation of these cuffs may still contribute to tracheal injuries. If the size of the granuloma is limited, the lesion is treated by excision (microlaryngeal surgery) under general anaesthesia. Using jet ventilation during the operation minimizes the trauma caused by intubation and reduces the risk of oedema and the risk of barotrauma, as it provides ventilation over a possible stenosis. In addition to providing better visualization of the surgical field and superior surgeon comfort, jet ventilation also increases the success of the operation. In this case report, we aimed to present a successful anaesthesia technique performed by jet ventilation in a patient with a postintubation granuloma, which was excised by microlaryngeal surgery without the need for reintubation. PMID- 27366424 TI - The Role of Preoperative Evaluation for Congenital Methemoglobinemia. AB - Preoperative care includes a clinical examination before invasive or non-invasive interventions for anaesthesia/analgesia and is the responsibility of the anaesthesiologists. Methemoglobinemia should be considered, as well as cardiac, pulmonary, and peripheral circulatory disorders in patients with central cyanosis and low oxygen saturation despite treatment with sufficient oxygen during anaesthesia. Methemoglobinemia is a serious clinical condition, associated with increased blood methemoglobin levels characterized by clinical signs, such as cyanosis and hypoxia due to lack of oxygen-carrying capacity. Here, we present our anaesthesia management in a patient with unnoticed congenital methemoglobinemia during preoperative evaluation, in whom clinical signs of methemoglobinemia developed after local anaesthesia administration before the surgery. PMID- 27366425 TI - Anaesthetic Management with Thromboelastography in a Patient with Glanzmann Thrombasthenia. AB - Glanzmann thrombastenia (GT) is a rare disease of an autosomal recessive inheritance characterized with fatal bleeding tendency. The anaesthesiologist should be cognizant of the risk involved and be prepared with necessary measures. In this paper, we present a GT case of a 9-year-old male with hypospadias, which was successfully repaired after platelet transfusions according to the thromboelastography tracings. PMID- 27366426 TI - Anaesthetic Management in Obstructive Sleep Apnoea Syndrome for Adenotonsillectomy. AB - The anaesthetic management of adenotonsillectomy in children with obstructive sleep apnoea syndrome is characteristic due to respiratory and cardiac side effects. A detailed physical examination in the preoperative period should be performed, including children's respiratory and cardiac systems. If they have an active infection, surgery should be postponed until the end of medical treatment. Preparation for difficult airway management should be done in the preoperative period. In this case, we presented a report of two children who had obstructive sleep apnoea syndrome, with airway management performed at the right lateral position to prevent the pharyngeal collapse and rapid sequence intubation performed using a short-acting muscle relaxant. PMID- 27366427 TI - E-Learning Materials are not yet Subject to Peer Review. PMID- 27366428 TI - The Professional Experience of Anaesthesiologists in Proper Inflation of Laryngeal Mask and Endotracheal Tube Cuff. AB - OBJECTIVE: Cuffs inflated to inappropriately high pressures cause ischemia, reducing tracheal mucosal blood flow, while cuffs inflated at lower pressure than necessary give rise to inadequate ventilation, aspiration of gastric contents, or extubation due to air leakage. In this study, we aimed to investigate the effect of the experience of anaesthesia staff on endotracheal tube and laryngeal mask airway cuff inflation. METHODS: The study included 348 elective patients scheduled to undergo surgery under general anaesthesia, with 34 anaesthesia technicians, 16 anaesthesia residents, and 12 anaesthesiologists with different years of professional experience. The participants were told to inflate the cuff balloon with air to the level of the pressure that was appropriate for them. No information was provided to the participants about the values of the cuff pressure pending the completion of all measurements. After placement of the laryngeal mask airway and endotracheal tube, the success of the procedure was checked by monitoring square-wave capnograph tracing and thoracoabdominal motion. Each participant performed the procedures on three patients, and the mean cuff pressures were measured. RESULTS: There was no significant correlation between duration of experience of technicians, residents, and experts in using laryngeal mask airway pressure (r=-0.192/p=0.278, r=0.225/p=0.402, r=-0.476/p=0.118, respectively) and endotracheal tube (r=-0.306/p=0.079, r=-0.060/p=0.826, r= 0.478/0.116, respectively). CONCLUSION: It has been concluded that professional experience does not contribute to achieving normal cuff pressure without monitoring. Introduction of the cuff manometer into routine anaesthesia practice will be useful, irrespective of anaesthesiologists' experience. PMID- 27366429 TI - Rapid Detection of Acute Kidney Injury by Urinary Neutrophil Gelatinase Associated Lipocalin in Patients Undergoing Cardiopulmonary Bypass. AB - OBJECTIVE: Acute kidney injury (AKI) is common following cardiopulmonary bypass (CPB). The aim of this study is to determine the accuracy of urinary neutrophil gelatinase-associated lipocalin (NGAL) levels following cardiac surgery to establish the severity of renal impairment as compared to serum creatinine levels. METHODS: A total number of 28 patients undergoing elective cardiopulmonary bypass were included. Diagnostic criteria of AKI was established in case of a percentage increase in serum creatinine concentration of >50%. Serum creatinine levels were recorded in the preoperative period before induction and in the postoperative period at 24, 48, and 72 hours. Urinary NGAL measurement was performed before induction and in the 4(th) postoperative hour. The duration of CPB surgery, hospital stay, and cross-clamp time were recorded. RESULTS: Based on AKI criteria, subjects were grouped as AKI (n=11) and no AKI (n=19). Postoperative urinary NGAL levels were significantly higher in the group with AKI (11.8 ng mL(-1) vs. 104.0 ng mL(-1), p=0.003). In the AKI group, CPB time bypass (111.9 min vs. 82.7 min) and cross-clamp time (76.9 min vs. 59.1 min) were significantly higher. A cut-off of 25.5 ng mL(-1) yielded a sensitivity of 81.82% and a specificity of 94.12% at the postoperative 4(th) hour with an AUC of 0.947 for predication of AKI. CONCLUSION: Urine NGAL rose significantly much earlier as compared to serum creatinine levels in the early postoperative period. Although larger case series are needed, we are of the opinion that urinary NGAL measurements may be used as an early clinical marker of AKI following CPB. PMID- 27366430 TI - Effects of High-Dose Rocuronium on the QTc Interval During Anaesthesia Induction in Patients Undergoing Coronary Artery Bypass Graft Surgery. AB - OBJECTIVE: Existing myocardial damage in coronary artery disease patients causes prolonged QT syndrome. The primary objective of this trial is to explore the effects of different doses of the muscle relaxant agent rocuronium (0.6 mg kg(-1) and 1.2 mg kg(-1)) on QTc following anaesthetic induction. The second objective is to determine the incidence and kinds of arrhythmias. METHODS: In this prospective and randomized trial, patients undergoing elective coronary artery revascularization surgery were included in one of two groups. Both groups took the same anaesthetic induction agents: midazolam and fentanyl. Rocuronium was administered in Group 1 (n=20) with dose of 0.6 mg kg(-1) and in Group 2 (n=20) with a dose of 1.2 mg kg(-1) for muscle relaxation. Heart rate, average arterial pressure and QTc were recorded before induction (T0), after induction (T1), after muscle relaxant (T2), and 2 minutes (T3) and 5 minutes after intubation (T4). RESULTS: QTc was significantly longer 2 minutes after intubation (in Group 1 and Group 2, respectively, 447.9+/-28.3 and 466.1+/-37.8 ms) than at the beginning (respectively, 426.9+/-25.7, 432.0+/-35.5 ms) (p<0.01). In the intergroup comparison, average QTc values were similar in all trial periods (p>0.05). The prevalence of arrhythmias in between Group 1 (35%, n=7) and Group 2 (15%, n=3) was similar (p=0.06). Arrhythmias were recorded 2 minutes after intubation in both groups (n=10, 25%). CONCLUSION: In patients undergoing coronary artery revascularization surgery, rocuronium doses of 0.6 mg kg(-1) and 1.2 mg kg(-1) prolong the QTc interval after intubation. Cardiac arrhythmias related to long QTc arising after intubation should be taken into consideration. PMID- 27366431 TI - Comparison of LMA CTrach and Video Laryngoscope in Endotracheal Intubation. AB - OBJECTIVE: In this study, our objective was to compare the Cormack and Lehane (C L) sight scores of direct laryngoscopy in endotracheal intubation with the endoscopic sight scores of the LMA CTrach and video laryngoscope. We also compared the success of endoscopy with the LMA CTrach and video laryngoscopy, intubation time, and its effects on haemodynamic and stress responses. METHODS: The study included 100 patients, with American Society of Anesthesiologists (ASA) scores I-III and aged 18-65, who will undergo elective surgery. Patients were randomly divided into two groups: Group C and Group V. The patients in both groups underwent direct laryngoscopy with a Macintosh laryngoscope, and their C-L scores were recorded. In Group C, the patients were intubated with the LMA CTrach, and in Group V, the patients were intubated with a video laryngoscope. Patients' haemodynamic parameters, oxygen saturation, end-tidal carbondioxide, and endoscopic sight scores were recorded. RESULTS: The demographic characteristics and the ASA classifications of the groups were similar. When endoscopic sight scores were compared with C-L, better sight was obtained in the LMA CTrach group; no significant difference was detected in Group V. Regarding the success of the intubation, no significant difference was detected between groups. However, when intubation times were compared, there was a significant difference between groups. The intubation time was longer in Group C. There was no difference between groups in terms of the percentage changes of haemodynamic parameters, oxygen saturation, and end-tidal carbondioxide values of the patients. CONCLUSION: In this study, when endoscopic sight scores were compared, better visualization was obtained in the LMA CTrach group. Therefore, in cases where intubation is difficult to apply in patients, the LMA CTrach can be an alternative application. PMID- 27366432 TI - Comparison of Spinal Anaesthesia and Paravertebral Block in Unilateral Inguinal Hernia Repair. AB - OBJECTIVE: We aimed to compare the efficacy of spinal anaesthesia (SA) and paravertebral block (PVB) in unilateral inguinal hernia repair. METHODS: Sixty American Society of Anesthesia physical status (ASA) I-III patients aged between 18-64 years with unilateral inguinal hernia were enrolled in this study. Two patients in Group SA and 4 patients in Group PVB were excluded, and statistical analyses were done on 54 patients. In regard to anaesthetic choice, patients were divided into two groups, with 30 patients in each: Group SA, spinal anaesthesia and Group PVB, paravertebral block. Standard monitoring was done, and mean arterial pressure (MAP) and heart rate (HR) were recorded during the surgical procedure. Demographic variables, surgical data, patient satisfaction, the onset times to reach T10 dermatome and to reach peak sensory level, and onset time to reach modified Bromage 3 motor block were recorded. Postoperative nausea and vomiting and pain at postoperative hours 0-24 with the visual analog scale (VAS) were also measured. RESULTS: Compared to pre-anaesthesia measurements, the decrease in HR and MAP during the 10(th)-90(th) minute period was significant in Group SA (p<0.01). In Group PVB, sensory block duration time was higher, whereas paralysis rate was higher in Group SA (p<0.01). Bromage scores were significantly different between the groups (p<0.01). In Group SA, VAS score at the 24(th) postoperative hour, nausea, and vomiting were significantly higher compared to Group PVB (p<0.01). CONCLUSION: In conclusion, paravertebral block provides acceptable surgical anaesthesia, maintaining good quality and long duration on postoperative analgesia in unilateral hernia repair. PMID- 27366434 TI - A Venous Catheter Complication: Venous Perforation and Lung Injury. AB - Central venous catheters are frequently used for different causes, like fluid infusions, haemodialysis, and measurement of central venous pressure. Complications that occur at the time or after the placement of these catheters can give harm to the patient or can cause need for a new attempt. Complications, like malfunction of the catheter, arterial puncture, haemothorax, or pneumothorax, can be seen in 5%-26% of the patients, and early detection is very important. We want to present a venous perforation and lung injury case according to the catheter based upon the literature. PMID- 27366433 TI - The Comparison of Patient-Controlled Remifentanil Administered by Two Different Protocols (Bolus and Bolus+Infusion) and Intramuscular Meperidine for Labor Analgesia. AB - OBJECTIVE: Nowadays, there are many pain relief methods for reducing the pain and stress of labor and delivery. In our study, two different remifentanil protocols (bolus and bolus+infusion) administered by patient-controlled analgesia method were compared with intramuscular meperidine for labor analgesia. METHODS: Ninety parturients who were scheduled for vaginal delivery were included in this study. Patients were randomly divided into 3 groups, with 15 primiparous and 15 multiparous patients in each group. Whenever a patient requested analgesics during the labor, Group M was given 1 mg kg(-1) intramuscular meperidine, Group B was given intravenous bolus patient-controlled remifentanil, and Group IB was given intravenous bolus+infusion patient-controlled remifentanil. Patients' systolic and diastolic blood pressure, heart rate, pain-comfort and sedation scores, remifentanil consumption, side effects, and Apgar scores of the newborns were evaluated during the labor and delivery. RESULTS: Patients' mean pain and comfort scores were significantly lower in Groups B and IB than in Group M at all time intervals except the first minute. Compared with Group IB, mean pain and comfort scores at 15, 30, 60, and 120 minutes were significantly higher in Group B. The mean sedation scores were similar among the groups. Total remifentanil consumption was lower in Group IB than in Group B, but it was not statistically significant. CONCLUSION: Patient-controlled intravenous bolus or bolus+infusion remifentanil provided more effective analgesia and patient comfort than intramuscular meperidine for labor analgesia. Especially during labor, bolus+infusion remifentanil administration provided better pain and patient comfort scores than bolus alone, without increasing remifentanil consumption. PMID- 27366435 TI - Inadvertent Administration of Neostigmine-Atropine Mixture from Epidural Catheter. AB - Most of the errors encountered during drug applications of anaesthesia may arise from the selection of the wrong syringe and ampule, confusion of epidural and intravenous line, or incorrect dose administration. In this case report, accidental application of reversal drugs via epidural catheter to a patient who was operated on for ureterovesical stenosis is presented. We aimed to indicate the drug errors in anaesthesia practices and discuss measures to be taken to prevent it. PMID- 27366436 TI - The Decrease of the Duration of Stay in the ICU with Rib Fixation in a Case of Multiple Rib Fracture. AB - Severe breathing problems arise in multiple rib fractures. As a result, many advantages of the surgical stabilization of the chest wall have been reported. Especially, shortening mechanical ventilation, along with a decrease in the duration of intensive care unit stay, is important for the prevention of possible infection complications. In this study, the dramatic improvement of the breathing pattern, as well as the reduction in ventilator duration after rib fixation time, of a 36-year-old patient with severe respiratory distress who had multiple rib fractures due to a road traffic accident was discussed. Due to this fact, it is concluded that patients could be discharged from the hospital earlier and uncomplicated as a result of fixation of the rib with the right indications. PMID- 27366437 TI - Parkinson's Disease and Spinal Anaesthesia. AB - Parkinson's is a neurodegenerative disease characterized by increased activity of GABA in basal ganglia and the loss of dopamine in nigrostriatum, associated with rigidity, resting tremor, gait with accelerating steps, and fixed inexpressive face. Being a neurological disease, spinal anaesthesia is often avoided in Parkinson's. Yet, in Parkinsons' patients, general anaesthesia may mask neurological symptoms in the intraoperative period and exacerbate them postoperatively. Moreover, the drugs administered in general anaesthesia more likely interact with anti-Parkinson drugs and may have side effects. With spinal anaesthesia, unlike general anaesthesia, because muscle relaxants and opioids are avoided, the exacerbation is not going to be masked due to muscle relaxation, and neurological symptoms may be distinguished clinically. In addition, the known effects of spinal anaesthesia, like suppression of surgical stress, postoperative pain relief, and early mobilization, may be advantageous in Parkinson's disease. Treated for Parkinson's disease for about 10 years at the age of 77 and with American Society of Anesthesiologists physical classification III (hyperlipidemia, hypertension, coronary artery disease, and chronic obstructive lung disease), a female patient was scheduled for elective surgery for fracture of the left distal tibia. In this case, we aimed to report a patient with Parkinson's disease who underwent spinal anaesthesia in order to avoid the disadvantages of general anaesthesia and reviewed the literature. PMID- 27366438 TI - Postoperative Sudden Hypotension Due to Relative Adrenal Insufficiency. AB - Systemic blood pressure is regulated by three mechanisms: the sympathetic nervous system, the renin-angiotensin system, and the arginine-vasopressin system. Hypotension is a condition that can occur at any stage of management of general anaesthesia, including induction, extubation, and maintenance. Many of the medications used for anaesthesia produce a mild to moderate decrease in systemic vascular resistance (SVR) with a subsequent decrease in arterial blood pressure. Profound and sustained hypotension, however, can have a global impact, resulting in a failure to adequately perfuse systemic capillary networks. The following report describes the case of a 69-year-old man undergoing surgery for total hip replacement who had hypotension that was refractory to fluid administration and inotropic agents at the end of the surgery. In this case study, the role of methylprednisolone therapy in catecholamine-resistant hypotension is also discussed. PMID- 27366439 TI - Olanzapine-Induced Malignant Neuroleptic Syndrome. AB - Neuroleptic malignant syndrome (NMS), caused by antipsychotic therapy, shows itself with mental status alteration, high fever, autonomic dysfunction, and muscle rigidity. It is a rare idiosyncratic reaction with mortality risk. The etiology is still unknown. NMS-related mortality and morbidity can be decreased by cessation of the used drug and aggressive treatment. Olanzapine is a thienobenzodiazepine, a member of atypical antipsychotic drugs; its structure and effects on neurotransmitters resemble clozapine. Here we report a case of bipolar disorder receiving olanzapine therapy for 10 years, who developed NMS without rigidity. We emphasized the importance of early hydration and hemodiafiltration therapy. PMID- 27366440 TI - Bispectral Index Guided Sedation in Congenital Pain Insensitivity Syndrome. PMID- 27366442 TI - Anaesthesia Management During Interventional Bronchoscopic Procedures: Laryngeal Mask Airway or Rigid Bronchoscope. AB - OBJECTIVE: Interventional bronchoscopy procedures are novel and effective modes of diagnosing and treating airway lesions. Airway management and ventilation are a major concern, especially when considering the fire hazard of ventilating during endobronchial thermal therapies. The aim of this study was to evaluate the usage of laryngeal mask airway (LMA) compared to rigid bronchoscopy for the ventilation of patients undergoing diagnostic or therapeutic interventional bronchoscopy procedures. METHODS: During this prospective randomised clinical trial study, patients were randomly allocated to two groups for ventilation: LMA and rigid bronchoscopy. Vital signs, including blood pressure, heart rate and percentage of blood O2 saturation before and during the procedure, degree of sore throat after recovery and physician's satisfaction, were recorded. RESULTS: A total of 83 patients, including 45 in the "LMA" and 38 in the "rigid" groups, were enrolled in this study. Their mean age was 51+/-17 years, and 59 (71%) were male. There was a statically significant difference between "rigid" and "LMA" categories regarding the decrease in O2 during the procedure in proportion to baseline figures (p=0.028). Haemodynamic parameters were better maintained using LMA compared to rigid bronchoscopy. CONCLUSION: Laryngeal mask ventilation maintains better oxygenation and haemodynamic stability and ensures physicians' and patients' satisfaction regarding ease of use, airway access and fewer complications compared to rigid bronchoscopy. Therefore, LMA can be introduced as a reliable alternative for ventilation during interventional airway procedures. PMID- 27366441 TI - Sepsis and Acute Kidney Injury. AB - Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically "Risk-Injury Failure-Loss-Endstage" (RIFLE), "Acute Kidney Injury Netwok" (AKIN) and "The Kidney Disease/ Improving Global Outcomes" (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also "cell cycle arrest" molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated. PMID- 27366443 TI - Comparison of the Haemodynamic Effects of Three Different Methods at the Induction of Anaesthesia. AB - OBJECTIVE: Haemodynamic variations are inevitable during induction of anaesthetic drugs. The present study investigates the haemodynamic variations of three different drugs (thiopental, propofol, and etomidate) used for induction of general anaesthesia together with fentanyl. METHODS: In a randomized, double blind study, 45 patients were assigned to one of three groups (n=15 each). Fentanyl 1 MUg kg(-1) was injected over 60 sec followed by propofol 2 mg kg(-1) (Group P), thiopentone 6 mg kg(-1) (Group T), or etomidate 0.3 mg kg(-1) (Group E). Noninvasive measurements of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), and heart rate (HR) was performed on admittance, immediately before the induction of anaesthesia, and 1, 3, and 5 min thereafter. Cardiac output (CO) values were recorded before induction, immediately after the injection of the drug, and at 1 min after the intubation. RESULTS: In all groups, during the study period, SAP, DAP, MAP, and CO values decreased with respect to time before induction. Following the administration of the induction dose of propofol (Group P), a significantly greater decrease of systolic and diastolic blood pressure was observed with etomidate (Group E) or thiopentone (Group T). Decrease in CO was also more marked with propofol (Group P) than with etomidate (Group E) or thiopentone (Group T). CONCLUSION: It's concluded that, in this study, the combination of fentanyl etomidate is safer than both the groups of fentanyl-propofol and fentanyl thiopental in terms of providing haemodynamic stability. PMID- 27366444 TI - Predictive Factors Involved in Development of Postoperative Pulmonary Complications. AB - OBJECTIVE: In the present study, we applied the method of the multi-center Prospective Evaluation of a Risk Score for postoperative pulmonary Complications in Europe (PERISCOPE) study, which was designed to predict postoperative complications and funded by the European Society of Anaesthesiology, to patients in our institution with the aim of prospectively analyzing the postoperative risk factors of pulmonary complications. METHODS: One hundred patients over 18 years of age who had emergency or elective non-thoracic or non-obstetric surgery under general anaesthesia or neuraxial blocks were included in the study. Collected data regarding the preoperative and postoperative period were filled in separate forms for all patients. RESULTS: A total of 11 patients developed pulmonary complications. We observed respiratory failure in 8 patients, pleural effusion in 3 patients, atelectasis in 5 patients, bronchospasm in 3 patients, and pneumothorax in 1 patient. In the univariate logistic regression model, patient age, gender, weight, rate of preoperative respiratory symptoms, cough test results, American Society of Anesthesiology (ASA) score, and the duration of surgery did not significantly increase the complication risk (p>0.05). However, in the univariate logistic regression model, the presence of respiratory symptoms increased the risk for complications approximately 5.34-fold (p=0.014). There was an increase in the possibility of complications in parallel with the increase in the duration of postoperative hospital stay (p=0.012). More respiratory symptoms (p=0.019) and longer hospital stay (6.5 vs. 3.5 days respectively, p=0.029) were recorded in patients with postoperative pulmonary complications. CONCLUSION: Considering patients undergoing non-thoracic or non-obstetric surgery, the prevalence of postoperative pulmonary complications is higher in patients diagnosed with respiratory symptoms in the preoperative period. These complications significantly extend the length of hospital stay. PMID- 27366445 TI - Does the Method and Timing of Intravenous Ketamine Administration Affect Postoperative Morphine Requirement After Major Abdominal Surgery? AB - OBJECTIVE: Single intravenous bolus administration and postoperative or perioperative infusions are the most preferred methods of ketamine. Nevertheless, there is no clear explanation on the ideal ketamine administration method. In this study, we aimed to compare the effects of the most common ketamine administration methods and administration time on postoperative opioid consumption. METHODS: Fifty-two patients undergoing colectomy for colon cancer were randomly assigned into four groups. Group 1 was the control group. Group 2 received only a single intravenous bolus dose of 0.5 mg kg(-1) ketamine at induction. Group 3 received 0.5 mg kg(-1) intravenous ketamine bolus at induction and perioperative ketamine infusion at a rate of 0.25 mg kg(-1) h(-1). Group 4 received a bolus of 0.5 mg kg(-1) intravenous ketamine at induction and perioperative and postoperative ketamine infusion at a rate of 0.25 mg kg(-1) h( 1). Postoperatively, visual analogue scale pain scores, side effects, and morphine consumption were recorded. RESULTS: There was no statistically significant difference in postoperative pain scores. Total morphine consumption was found to be significantly lower in Group 4 compared to the other groups (p=0.03, p=0.004, p=0.03, respectively). During the 1(st), 2(nd), and 4(th) hours in the postoperative period, patient-controlled analgesia morphine consumption was significantly lower in Group 4 compared to the control group (p<0.01). CONCLUSION: Preoperative single-bolus dose or intraoperative low-dose ketamine infusion does not decrease postoperative morphine consumption; however, per- and postoperative 48-hour ketamine infusion has a significant effect in decreasing morphine consumption without decreasing the incidence of side effects in patients undergoing major abdominal surgery. PMID- 27366446 TI - The Evaluation of Applied Anaesthetic Techniques for Caesarean in Parturients with Cardiac Diseases: Retrospective Analysis. AB - OBJECTIVE: In this study, the effects of anaesthetic technique on mother and newborn were investigated in a retrospective analysis of parturients with cardiac diseases undergoing Caesarean section between 2006-2012. METHODS: Our hospital's medical information system records were analyzed, and we found 107 parturients with cardiac disease and were undergoing Caesarean section, and their demographic data and obstetric, anaesthetic, and neonatal record forms were inspected. RESULTS: Fifty-three (49.5%) pregnant women received general anaesthesia, and 54 (50.5%) received regional anaesthesia (34 spinal, 19 epidural and 1 CSE) (p=0.05). Week of pregnancy was lower for the group of general anaesthesia (p=0.007). Among cardiac parturients, valvular lesion rates were higher (75.7%). The relationship between existing cardiac disease and anaesthetic management was not significant (p=0.28). However, we determined that parturients with higher NYHA (New York Heart Association) classifications had higher general anaesthesia rates. (p=0.001). A rate of 39% of 74 NYHA I patients were undergoing general anaesthesia; this rate was 64% for NYHA II and 100% for NYHA III. The patients with cardiac surgery or medical treatment history had higher general anaesthesia rates (p=0.009). Although the general anaesthesia group newborn weights were lower (p=0.03), there was no difference between groups for APGAR scores. With regard to postoperative complications and hospital stay, the groups were similar. CONCLUSION: We determined that general and epidural rates in parturients with cardiac diseases were similar, general anaesthesia was preferred for parturients who had higher NYHA classifications and surgical or medical treatment history. We considered that general anaesthesia criteria should reduce the anaesthesia management of parturients with cardiac disease; epidural or CSE anaesthesia applications should increase according to the patient's physical state, haemodynamic parameters, and obstetric indications. PMID- 27366447 TI - Parental Satisfaction Assessment After Paediatric Procedural Sedation: There Are Still Issues to Address. AB - OBJECTIVE: As paediatric sedation practices are becoming safer and more feasible everyday, they have been widely used for diagnostic and therapeutic procedures. This study intended to determine the relation between parental satisfaction and the branches applying procedures and demographic data of the patients and their families, physicians, nurses, and the healthcare personnel in the room. METHODS: In total, 223 successive patients under 18 years of age and ASA I-II undergoing diagnostic or therapeutic procedures in paediatric pulmonary disease, gastroenterology, cardiology, and invasive radiology units were included in the study. The satisfaction level of the patients' parents was determined through a questionnaire of 22 questions. RESULTS: Average satisfaction scores for paediatric bronchoscopy and endoscopic interventions varied between 8.06 and 9.30, while the satisfaction scores of the interventions for the cardiovascular system, hepatic system, and renal system, as well as the invasive radiologic interventions, varied between 7.5 and 9.6. There was a statistically significant negative correlation between the age of parents and children and the necessity for a playground in the waiting area (p<0.05). A significant correlation was found between the age of children and the adequacy of the anaesthetist's behaviors (p<0.05). CONCLUSION: Satisfaction levels of the parents were high at the units where paediatric sedation was applied. However, the expectations of young patients and their parents were higher. When the physical conditions and communication with patients and their relatives are improved and the process schedules are followed more precisely, the clinical results will increase in a positive way. PMID- 27366448 TI - Technology and Information Tool Preferences of Academics in the Field of Anaesthesiology. AB - OBJECTIVE: Researchers use a large number of information technology tools from the beginning until the publication of a scientific study. The aim of the study is to investigate the technology and data processing tool usage preferences of academics who produce scientific publications in the field of anaesthesiology. METHODS: A multiple-choice survey, including 18 questions regarding the use of technology to assess the preferences of academicians, was performed. RESULTS: PubMed has been the most preferred article search portal, and the second is Google Academic. Medscape has become the most preferred medical innovation tracking website. Only 12% of academicians obtain a clinical trial registration number for their randomized clinical research. In total, 28% of respondents used the Consolidated Standards of Reporting Trials checklist in their clinical trials. Of all participants, 21% was using Dropbox and 9% was using Google-Drive for sharing files. Google Chrome was the most preferred internet browser (32.25%) for academic purposes. English language editing service was obtained from the Scribendi (21%) and Textcheck (12%) websites. Half of the academics were getting help from their specialist with a personal relationship, 27% was doing it themselves, and 24% was obtaining professional assistance for statistical requirements. Sixty percent of the participants were not using a reference editing program, and 21% was using EndNote. Nine percent of the academics were spending money for article writing, and the mean cost was 1287 Turkish Liras/year. CONCLUSION: Academics in the field of anaesthesiology significantly benefit from technology and informatics tools to produce scientific publications. PMID- 27366449 TI - Perioperative Anaesthetic Approach in a Homozygous Sickle Cell Anaemia Patient with Frequent Pain Crises. AB - Sickle cell disease (HbS) is a haemolytic anaemia characterized by the formation of abnormal haemoglobin. In patients with sickle cell disease, high rates of erythrocyte generation, degradation, and hyperbilirubinemia increase the risk for cholelithiasis. Previous studies have found that the incidence of cholelithiasis is 70% in adult patients. In sickle cell disease, decreased oxygen concentration leads to the sickling of erythrocytes by causing aggregation and polymerization. Sickle erythrocytes can have devastating effects on many vital organs by causing microvascular occlusion. In patients with sickle cell anaemia, anaesthetic technique, anaesthetic agents, and surgical trauma may cause additional risk. In this case report, we present a perioperative anaesthetic approach in the laparoscopic cholecystectomy of a patient with HbS, elevated liver function tests, and frequent pain crises. PMID- 27366450 TI - Glidescope Video Laryngoscope Use for Tracheal Intubation in a Patient with CHARGE Syndrome. AB - CHARGE syndrome is an autosomal dominant syndrome in which ocular coloboma (C), heart defects (H), choanal atresia (A), growth retardation (R), genital hypoplasia (G), ear abnormalities (E), and tracheoesophageal fistula, dysphagia, cleft palate, micrognathia, facial paralysis, hypopituitarism, and brain abnormalities may be seen in patients. The patients with CHARGE syndrome face surgical procedures many times from birth. Especially, the problems we meet in the airway may be special. In this case report, we aimed to share our experience of endotracheal intubation performed with Glidescope video laryngoscopy for a patient at the age of 20 months, weight 7.5 kg and height 70 cm, with CHARGE syndrome who was undergoing cochlear implantation. PMID- 27366451 TI - The Anaesthetic Management of a Patient with Maple Syrup Urine Disease. AB - Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder caused by a deficit of oxidative decarboxylation of branched-chain aminoacids. It leads to a build-up of leucine, isoleucine, valine, and toxic metabolites in blood and urine, progressing to acute and chronic brain dysfunction. The first symptoms appear in early childhood and are characterized by sweet-smelling urine, with an odor similar to that of maple syrup. At birth, infants seem healthy, but if untreated, they may suffer from neurological deterioration, seizures, hypertonia, or ataxia. During stressful situations, such as infection or surgery, patients may experience severe ketoacidosis, rapid neurological deterioration, and hypoglycemia. We report the anaesthetic management in a child patient with MSUD, admitted for peritonal dialysis catheter insertion with general anaesthesia. PMID- 27366452 TI - Management of the Difficult Paediatric Airway with a Simple Fiberoptic-Assisted Laryngoscope: A Report of Two Cases with Pierre Robin and Patau's (Trisomy 13) Syndrome. AB - Airway management of children with congenital craniofacial anomalies is a challenge for paediatric anaesthesiologists. We do not have any video-assisted airway device in our department for difficult paediatric intubations. We decided to attach a regular fiberoptic (outer diameter; 3.7 mm, Karl Storz, Germany) scope to a conventional Macintosh Laryngoscope (size 1). We describe two cases of Pierre Robin and Patau's (Trisomy 13) syndrome successfully intubated with a fiberoptic-assisted laryngoscope (FOL). A fiberoptic scope and any size of a laryngoscope blade can be easily assembled in the operating room. The FOL may be a useful device in the setting of difficult paediatric intubation. PMID- 27366453 TI - Anaesthesia Management of a Child with West Syndrome. AB - West syndrome (WS) is an epileptic encephalopathy usually occurring during the first year of life and is characterized by severe electroencephalography (EEG) derangement. Most of these patients may develop cerebral palsy, facial malformations, and skeletal deformities. The anaesthesiologist should make the preoperative assessment carefully due to epileptic seizures and should consider the possibility of difficult intubation because of coexisting anatomic malformations during the anaesthesia management of patients with WS. This report presents a case of general anaesthesia management in a left femoral fixation operation in an 11-year-old, 18 kg male patient. PMID- 27366454 TI - Limited-Form Wegener Granulomatosis Case: Anaesthetic Approach and Literature Review. AB - Wegener granulomatosis (WG) is a kind of vasculitis that affects small and medium sized arteries. Necrotizing granulomatous vasculitis of the upper and lower respiratory tracts and necrotizing glomerulonephritis of the kidneys are present. WG affects mainly Caucasian individuals between 15-75 years old, with a mean age of onset of 41 years. It affects both males and females equally. Kidney involvement is not present in the limited form of WG. Peripheral nerve blocks are good alternatives when general anaesthesia is risky. Popliteal block is blockade of the sciatic nerve at the popliteal region. Popliteal block is a kind of peripheral block for surgeries below the knee level. In this article, we report on the anaesthesia management of a 61-year-old limited-form WG patient for whom general anaesthesia was risky because of lung involvement. PMID- 27366455 TI - Difficult Airway Management in Osmed Syndrome. PMID- 27366456 TI - Intensive Care Treatment in Traumatic Brain Injury. AB - Head injury remains a serious public problem, especially in the young population. The understanding of the mechanism of secondary injury and the development of appropriate monitoring and critical care treatment strategies reduced the mortality of head injury. The pathophysiology, monitoring and treatment principles of head injury are summarised in this article. PMID- 27366457 TI - Sensitivity of the Combination of Mallampati Scores with Anthropometric Measurements and the Presence of Malignancy to Predict Difficult Intubation. AB - OBJECTIVE: The aim of this study was to determine the combinations of the Mallampati test and anthropometric measurements with the highest selectivity value. In addition, we aim to identify a possible correlation between head circumference measurement, the presence of malignancy and difficult intubation. METHODS: Patients who were scheduled to undergo elective surgery under general anaesthesia, who fell into Group 1-2 according to ASA criteria and were between the ages of 18-70 years were included in the study. Patients with Cormack-Lehane scores of 3-4 were considered to be difficult intubations. Thyromental distance, sternomental distance, mandibular distance, neck length, neck circumference and head circumference were measured during the anthropometric measurements. RESULTS: According to the ROC analysis, there was a significant difference in the thyromental distance, sternomental distance, neck length, neck circumference and head circumference between the easy and difficult intubation groups (p<0.05). The incidence of difficult intubation was 8.3% in patients with non-head-neck malignancies, whereas the incidence was 7.1% in patients without any malignancies. The difference between these groups was not statistically significant (chi(2)=0.101; p=0.751). CONCLUSION: To predict the incidence of difficult intubation, the test with the highest selectivity and highest positive predictive values was the combination of Mallampati-thyromental distance. We believe that the head circumference and neck length measurement, in addition to the current anthropometric measurements, may be crucial to predict the incidence of difficult intubations. In addition, we believe that the anticipation of difficult intubations in patients with non-head-neck malignancies is not different from the normal population. PMID- 27366458 TI - The Effect of Intravenous Magnesium Sulphate Treatment on the Spinal Anaesthesia Produced by Bupivacaine in Pre-eclamptic Patients. AB - OBJECTIVE: In our study, the effect of intravenous magnesium sulphate in normal and pre-eclamptic patients on spinal anaesthesia produced by bupivacaine was investigated. METHODS: Sixty-four pregnant (32 normal and 32 pre-eclamptic) were accepted in this study. Pregnants were divided into four groups as patients given intravenous magnesium sulphate and as control. Spinal anaesthesia was induced with 12.5 mg 0.5% hyperbaric bupivacaine. Intraoperative and postoperative haemodynamic variables, sensorial block periods, onset times of sensorial and motor block, maximum sensorial block levels, the time to reach maximum block level, Bromage scores, consumptions of intraoperative analgesic and ephedrine, the quality of anaesthesia, the duration of spinal anaesthesia and magnesium levels in blood and cerebrospinal fluid were measured and recorded. RESULTS: The level of magnesium in blood and cerebrospinal fluid was significantly higher in the group given magnesium in pre-eclamptic patients (p<0.01). Onset of sensory block times were significantly longer in intravenous magnesium group than in groups 1, 2 and 3 (p<0.05). Onset of motor block times were significantly longer and the duration of anaesthesia was shorter in groups given magnesium (p<0.05). Although the quality of anaesthesia was similar, supplemental analgesic consumption was significantly higher in pre-eclamptic pregnants given magnesium sulphate than in pre-eclamptic pregnants who were not given magnesium sulphate (p<0.05). CONCLUSION: Intravenous magnesium sulphate treatment during the spinal anaesthesia produced by bupivacaine extended the onset of sensory and motor block times, shortened the duration of spinal anaesthesia and therefore led to early analgesic requirement. PMID- 27366459 TI - The Effects of Preincisional Levobupivacaine Infiltration on Extubation Comfort, Postoperative Recovery and Visual Analogue Scale in Appendectomy Patients. AB - OBJECTIVE: The aim of our study was to determine the effect of preincisional 0.25% levobupivacaine infiltration on extubation comfort, postoperative recovery and visual analogue scale (VAS) in appendectomy patients. METHODS: Forty 15-60 year-old patients at American Society of Anaesthesiologists (ASA) physical status I-II, scheduled for appendectomy were included in the study. After routine monitorisation, anaesthesia induction was performed with propofol, fentanyl and rocuronium; later, maintenance was continued with sevoflurane. Patients were divided into two groups randomly. A total 20 mL of 0.25% (50 mg) levobupivacaine was injected around the incision line as a rectangle in Group 1. Levobupivacaine was not administered in Group 2 patients. Heart rate, peripheral oxygen saturation, additional fentanyl requirement and mean blood pressure were recorded during the operation. All patients were evaluated according to difficulties encountered during extubation. RESULTS: Discharge time, necessity of diclofenac and postoperative VAS values at 0-1 hours were statistically lower in Group 1 patients than the Group 2 patients (p<0.05). Difficulties, like straining, cough, laryngo-bronchospasm, vomiting and nausea during extubation, were 5% and 25% in Group 1 and Group 2, respectively, but these differences were not statistically significant (p=0.077). CONCLUSION: Infiltration of 0.25% of levobupivacaine as a rectangle which included the incision line before surgery decreases discharge time, provides analgesia well in the early postoperative period and diminishes the requirement of analgesics in appendectomy patients. PMID- 27366460 TI - Comparison of Transversus Abdominis Plane Block and IV Patient-Controlled Analgesia after Lower Abdominal Surgery. AB - OBJECTIVE: We aimed to compare the first 24-hour postoperative analgesic efficiency of ultrasound (USG)-assisted transversus abdominis plane (TAP) block to IV morphine patient-controlled analgesia (PCA) in patients undergoing lower abdominal surgery. METHODS: Fifty ASA I-III patients were included into this randomised, prospective clinical study. At end of surgery, Group 1 received 1 mg kg(-1) 0.5% bupivacaine and 1 mg kg(-1) 1% lidocaine in a 30-mL volume during TAP block. Group 2 received 1 mg kg(-1) tramadol IV 10 minutes before extubation, and PCA was started with 1 mL morphine IV at a concentration of 1 mg kg(-1) and a 10 min lock time. Visual analogue scale (VAS), heart rate (HR), respiratory rate, peripheral oxygen saturation (SpO2), additional analgesic need and nausea vomiting at the postoperative 30(th) minute and 1, 2, 3, 6, 12, and 24 hours were evaluated. In both groups, when VAS values were >4, patients were given 1 mg kg( 1) tramadol IV in first evaluation at the 30(th) minute or 15 mg kg(-1) paracetamol at other evaluations. RESULTS: No difference was observed between groups in terms of VAS values. No difference was observed in terms of HR in the within-group comparison, but Group 1 HR values were lower compared to Group 2 (p<0.01). No difference was observed in additional analgesic need at any times. Nausea-vomiting score was higher in Group 2 in the between-group comparison at the 30(th) minute (p<0.04), but no difference was observed after the 1(st) hour. CONCLUSION: Transversus abdominis plane block is effective as IV morphine-PCA in postoperative pain therapy in lower abdominal surgery, when given in a 30-mL volume. It may be preferable to IV-PCA, as the analgesic effect starts earlier and decreases the systemic effect of the morphine used in PCA. PMID- 27366461 TI - Experience of Laparoscopic Cholecystectomy Under Thoracic Epidural Anaesthesia: Retrospective Analysis of 96 Patients. AB - OBJECTIVE: Although the traditional anaesthesia method for laparoscopic cholecystectomy has been general anaesthesia, regional anaesthesia techniques are also successfully used today. In this paper, we aimed to report our experiences with thoracic epidural anaesthesia, including complications, postoperative analgesia, technical difficulties and side effects. METHODS: Between December 2009 and November 2012, 90 patients undergoing laparoscopic cholecystectomy were retrospectively analysed. Demographic data, American Society of Anesthesiologists (ASA) scores, comorbidities, duration of operations, medications and doses used for sedation were reviewed. RESULTS: The gender distribution of patients were recorded as 15 males (15%) and 81 females (85%). The patients had an average age of 46.74+/-13.28, an average height of 162.50+/-5.57 cm and a mean weight of 73.57+/-12.48 kg. ASA classifications were distributed as follows: ASA I: 63 (65%) patients, ASA II 28 (29%) patients and ASA III: 5 patients. We recorded 3 patients with chronic obstructive pulmonary disease (COPD), 14 patients with diabetes mellitus (DM) and 22 patients with hypertension who got their diagnosis in the perioperative visit. During the operation, three patients had bradycardia (heart rate 50 min(-1)), and atropine was applied. Ephedrine and fluid resuscitation had been applied to 3 patients for the treatment of intraoperative hypotension. Midazolam, ketamine hydrochloride and propofol were administered to patients for sedation during the operations. Thoracic epidural anaesthesia was performed at the level of T7 -9 intervertebral space with the patients in the sitting position. Patients were given oxygen by a face mask at a rate of 3-4 L min(-1). The pneumoperitoneum was created by giving carbon dioxide at the standard pressure of 12 mmHg into the abdominal cavity in all patients. If needed, postoperative analgesia was provided by epidural local anaesthetic administration. CONCLUSION: Thoracic epidural anaesthesia can be applied as an alternative to general anaesthesia for laparoscopic cholecystectomy. PMID- 27366462 TI - A Retrospective Analysis of Comparison of General Versus Regional Anaesthesia for Endovascular Repair of Abdominal Aortic Aneurysm. AB - OBJECTIVE: The aim of this study is to compare general anaesthesia (GA) versus regional anaesthesia (RA) for endovascular aneurysm repair (EVAR). METHODS: We analysed the files of 89 patients between August 2010-August 2012 who underwent elective EVAR retrospectively. RESULTS: We performed RA for 32 patients (36%) and GA for 57 patients (64%). The operations were completed successfully in both groups and did not require conventional surgery. The mean age of the patients was 71.5+/-7 (range 50-88 years). RA was preferred more than GA in the presence of advanced-stage chronic obstructive pulmonary disease statistically (p=0.032). The usage of vasodilator drug and atropine was found to be higher in the GA group than the RA group in the intraoperative period (p=0.001 and p=0.01, respectively). The intensive care unit (ICU) was necessary for 5 patients in the RA group (16%) and 13 patients for the GA group (23%) postoperatively (p=0.301). The median ICU stay in the RA group was 2 hours and 4.4 hours in the GA group (p=0.114). The median hospital stay was 2.63+/-1.91 days in the RA group and 2.04+/-1.16 days in the GA group, with no statistically significant difference between groups (p=0.120). There was no mortality of patients in either group for the peroperative period and the 30-day follow-up period. CONCLUSION: Our present study suggests that patient characteristics are more important than the anaesthetic method on the outcomes of EVAR. PMID- 27366463 TI - Anaesthetic Method Preference of Obstetricians for Caesarean Section. AB - OBJECTIVE: Anaesthesiologists are applying regional anaesthesia for caesarean section at an increasing rate compared to previous years. In our study, we tried to evaluate the perspective of obstetricians towards this trend. METHODS: Questionnaires were sent to e-mail addresses of obstetricians via the internet; 195 obstetricians replied. Sex, age, work place, employer, working durations as consultant, preference of anaesthesia for caesarean section and their bias towards regional anaesthesia were asked with these questionnaires. A 5-point Likert scale was used to evaluate their bias towards regional anaesthesia. RESULTS: While 82.1% of obstetricians (n: 160) preferred regional anaesthesia, 17.9% of obstetricians (n: 35) favoured general anaesthesia for caesarean section for both themselves and their primary relatives. However, 80% of the participants opted for regional anaesthesia for their patients; only 20% of the participants still preferred general anaesthesia for caesarean section. Chi-square tests that were used to evaluate the relationship between demographic data and anaesthesia choices of obstetricians for both themselves, their primary relatives and their patients did not reveal any statistically significant differences (p<0.05). CONCLUSION: A large portion of Turkish obstetricians consider regional anaesthesia a safe procedure and prefer it highly for both themselves and their patients. PMID- 27366464 TI - Takotsubo Cardiomyopathy Occurring in the Postoperative Period. AB - Takotsubo cardiomyopathy simulates acute myocardial infarction, and it is characterised by reversible left ventricular failure. A case of Takotsubo cardiomyopathy diagnosed after emergency angiography performed in a patient with evidence of acute myocardial infarction in the postoperative period will be described in this report. Transurethral resection of a bladder tumour (TUR-BT) was performed in a 92-year-old male patient by the urology clinic. The patient was transferred to the post-anaesthesia care unit after the operation. An echocardiography was performed because of the sudden onset of dyspnoea, tachycardia (140-150 beats per minute, rhythm-atrial fibrillation) and ST-segment elevation on electrocardiography (ECG) at the first postoperative hour, and midapical dyskinesia was detected at the patient. An immediate angiography was performed due to suspicion of acute coronary syndrome. Patent coronary arteries and temporary aneurysmatic dilatation of the apex of the heart were revealed by angiography. As a result of these findings, the patient was diagnosed with Takotsubo cardiomyopathy by the cardiology service. The patient was discharged uneventfully following 10 days in the intensive care unit. Aneurysm of the apex of the left ventricle and normal anatomy of the coronary arteries in the angiography have diagnostic value for Takotsubo cardiomyopathy. Diuretics (furosemide) and beta-blockers (metoprolol) are commonly used for the treatment of Takotsubo cardiomyopathy. Even though Takotsubo cardiomyopathy is a rare and benign disease, it should be kept in mind in patients suspected for acute myocardial infarction in the postoperative period. PMID- 27366465 TI - Anaesthesia Management of a Patient with Incidentally Diagnosed Diaphragmatic Hernia During Laparoscopic Surgery. AB - Diaphragmatic hernia is usually congenital. However, it is rarely traumatic and can stay asymptomatic. In this report, we aimed to present the anaesthetic management of a patient with diaphragmatic hernia due to previous trauma (14 years ago), which was diagnosed incidentally during surgery for rectal cancer. The patient (53 years, 56 kg, 165 cm, American Society of Anaesthesiologist (ASA) II), to whom laparoscopic surgery was planned because of rectal cancer, had a history of falling from a height 14 years ago. Preoperatively, the patient did not have any sign except small right diaphragmatic elevation on the chest x-ray. After induction, maintenance of anaesthesia was continued with sevoflurane and O2/N2O. The patient was given a 30 degrees Trendelenburg position. When the trochars were inserted by the surgeon, the diaphragmatic hernia was seen on the right part of the diaphragm, which was hidden by the liver. The surgery was continued laparoscopically but with low pressure (12 mmHg), because the patient did not have any haemodynamic and respiratory instability. The patient, who had stable haemodynamic parameters and no respiratory complications during the operation, was transferred to the ward for monitorised care. Traumatic diaphragmatic hernias can be detected incidentally after a long period of acute event. In our case, it was diagnosed during laparoscopic surgery. The surgery was completed with appropriate and careful haemodynamic monitoring and low intra abdominal pressure under inhalational anaesthesia without any impairment in the patient's haemodynamic and respiratory parameters. PMID- 27366466 TI - Continuous Spinal Anaesthesia for Hip Fracture Surgery in a High-Risk Patient. AB - Elderly patients have increased risk for perioperative mortality and morbidity due to additional comorbidities, such as cardiac diseases. Regional anaesthesia techniques are usually preferred in high-risk patients due to some advantages, such as the maintenance of cardiovascular stability and early postoperative mobilisation. This case presents the anaesthetic approach in a 55-year-old male patient with low ejection fraction that underwent hip fracture surgery. In this present case, continuous spinal anaesthesia with low-dose hyperbaric bupivacaine provided safe and effective anaesthesia during surgery with minimal haemodynamic changes and adequate analgesia during the first 24 hours after surgery. PMID- 27366467 TI - Cerebral Vein Thrombosis after Spinal Anaesthesia with Pregnancy. AB - Thrombosis of cerebral veins or thrombosis of cortical and deep veins that empty into the sinuses can cause serious neurological syndromes. Cerebral vein thrombosis is seen, especially between the ages of 20-35. The predisposing factors in 80% of patients can be determined. Pregnancy, postpartum period and spinal anaesthesia are among the predisposing factors. Diagnosis of the disease is difficult due to the variety of clinical signs and symptoms. Headache is the most common reason for admission to the hospital. Thromboembolic events in pregnancy are an important reason of maternal morbidity and mortality. Most cases of cerebral venous thrombosis in pregnancy occur in the postpartum period. Confusion, convulsions and respiratory arrest occurred in 37-year-old female patient after 3 hours from operation. Cerebral vein thrombosis was diagnosed, owing to laboratory and neuroradiological findings. In this article, we have emphasised the importance of clinical evaluation of pregnant patients with cerebral vein thrombosis after spinal anaesthesia. PMID- 27366468 TI - Endotracheal Tube Obstruction: A Manufacturing Defect. AB - Various manufacturing defects of endotracheal tubes are encountered in anaesthesia practice. One of the important defects of an endotracheal tube is that a partial or complete obstruction can be potentially life-threatening. Manufacturing defects may not be ascertainable by routine inspection. In this case report, we report a partial airway obstruction caused by a plastic membrane in the connector of an endotracheal tube as a manufacturing defect. PMID- 27366469 TI - Sudden Appearance of Water in Flowmeter During Air/Oxygen and Sevoflurane Anaesthesia. AB - Endotracheal intubation was performed, and a water bubbling sound was heard from the anaesthesia device immediately after the release of gases to administer the O2-air-sevoflurane mixture. The flowmeter on the anaesthesia device was then found to be filled with water. The breakdown of the dryer in the medical air compressor system was determined as the source of the problem, since a greasy fluid mixture was released from the air-wall outlets in all rooms. Consequently, the anaesthesia team should keep in mind that problems as seen in the current case might emerge and should be alert. PMID- 27366470 TI - The Effects of Desflurane and Propofol on the Release of Thyroid Hormones in Euthyroid Patients Undergoing Elective Lumbar Discectomy. AB - OBJECTIVE: In this study, we aimed to compare the effects of desflurane and propofol on the release of thyroid hormones in euthyroid patients undergoing single-level lumbar discectomy. METHODS: The study group included 21-65-year-old American Society of Anesthesiology (ASA) I-II euthyroid 40 patients undergoing elective single-level lumbar discectomy. They were randomly divided into 2 groups (n=20). In the maintenance of anaesthesia, Group D received desflurane inhalational anaesthesia and remifentanil infusion, and Group P received propofol and remifentanil IV infusions. Four blood samples for the determination of plasma levels of free triiodothyronine (FT3), free thyroxine (FT4) and thyrotropin (TSH) were collected 5 min before and 60 min after the induction of anaesthesia and 60 min and 24 h after the surgery. RESULTS: Plasma TSH levels in both groups reached the highest levels at the first postoperative hour and returned to the preoperative levels 24 hours after the surgery. Regarding plasma FT3 levels, there were no significant differences within and between groups. There were no significant differences in plasma FT4 levels within the patients of Group P, but in Group D, FT4 levels reached its peak in the first hour of anaesthesia induction and returned back to preoperative levels 24 hours postoperatively (p<0.05). CONCLUSION: Further studies are needed to confirm our findings and evaluate patients with thyroid gland pathologies. PMID- 27366471 TI - Cardiac and Liver Marker Alterations After Laparoscopic Gynaecologic Operations. AB - OBJECTIVE: In our study, we aimed to investigate the effect of laparoscopic procedures in which the abdominal cavity at a Trendelenburg position of 15 degrees was insufflated with CO2 on cardiac and liver markers. METHODS: Forty patients scheduled for laparoscopic gynaecological surgery were included in the study. Venous blood samples were taken the day before operation and 6 hours after surgery, and later, lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase-MB (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), myoglobin (MY) and d-dimer (d-D) were measured. RESULTS: There was no statistically significant difference in the values of preoperative and postoperative ALT (16.8+/-9.4 and 17.8+/-9.3; p=0.579), AST (19.4+/-7 and 20.9+/-7.6; p=0.361) and ALP (65.2+/-16.2 and 63.3+/ 16.9; p=0.609), but LDH (385.1+/-117.3 and 460.6+/-156.3; p=0.003), CK (113.8+/ 138.5 and 247.9+/-283.5; p=0.0001), CK-MB (22.8+/-13.3 and 28.7+/-16; p=0.011), MY (28.1+/-12.9 and 138.8+/-129; p=0.0001) and d-D (509.5+/-815: 1026+/-1054; p=0.0001) increased significantly. CONCLUSION: After laparoscopic operations in the Trendelenburg position, postoperative serum ALT, AST and ALP levels, remained unchanged, when compared to preoperative values, but LDH, CK, CK-MB, myoglobin and d-dimer values increased significantly. PMID- 27366472 TI - The Comparison of the Effects of Epidural Bupivacaine and Levobupivacaine on the Autonomic Nervous System and Cardiac Arrhythmia Parameters in Inguinal Hernia Surgeries. AB - OBJECTIVE: The aim of this study is to investigate the effects of bupivacaine and levobupivacaine, used to create epidural anaesthesia in inguinal hernia operations, on heart rate variability and cardiac arrhythmia parameters. METHODS: Sixty male patients of the American Society of Anesthesiology (ASA) I-II group, scheduled to be operated on for inguinal hernia surgery with epidural anaesthesia, were randomly divided into two groups. The patients, with a 12 channel Holter recorder (Rozinn RZ153+12-USA) attached 1 hour before the operation to record until the end of the surgery, were taken into the preparation room and anaesthetised. In group L (n=30), 17 mL of 0.5% levobupivacaine (Chirocain 0.5%-Abbot, El-verum, Norway) was given into the epidural space within 10 minutes, versus 17 mL of 0.5% bupivacaine in (Marcain 0.5%, Astra Zeneca, Istanbul, Turkey) group B (n=30). After 30 minutes, when there was enough block, the operation had been started. Holter recordings, starting 1 hour before the anaesthetic procedure and completed by the end of the operations, were transferred to the computer. The records were evaluated by the cardiologists. RESULTS: When analysing the frequency effect measurement results of the heart rate variability, it was seen that neither of the medications created any statistically significant change in or among the groups in total, very-low frequency (VLF), low-frequency (LF), high-frequency (HF) and LF/HF ratio levels. Only normalised low-frequency band was significantly lower in Group L (p=0.013). CONCLUSION: In the volumes and concentrations that were used in our study, levobupivacaine and bupivacaine created sensory blockade at the same level on average and did not reduce heart rate variability at the levels of these blockages. PMID- 27366473 TI - Comparison of Dexmedetomidine Versus Ketamine-Propofol Combination for Sedation in Cataract Surgery. AB - OBJECTIVE: The aim of this study is to compare the sedative properties and haemodynamic and respiratory effects of dexmedetomidine and a ketamine-propofol combination (ketofol), which are expected to have minimal effects on spontaneous breathing. METHODS: Sixty patients were enrolled in this prospective randomised study. Patients were divided into 2 groups according to the administration of dexmedetomidine (Group D) and ketofol (Group K). Target sedation level was determined as a Ramsay Sedation Score of 3. In Group D, 0.5 mcg kg(-1) dexmedetomidine was administered via intravenous route in 10 minutes versus 0.125 mL kg(-1) of a solution containing 200 mg propofol and 100 mg ketamine in Group K. Haemodynamic and respiratory effects, postoperative awakening time, analgesic properties and satisfaction levels of the patients and surgeon were assessed. RESULTS: There was a statistically significant decrease in mean arterial pressures following drug administration compared to initial measurements in both groups. However, there was a statistically significant decrease in heart rate only in Group D. There was no significant difference between the two groups regarding respiratory rate and protection of spontaneous respiration. Although the time for Aldrete score to be 9 was 16.1 minutes for Group K, it was 24.9 minutes for Group D, and this difference was statistically significant (p<0.01). There was no significant difference between the two groups regarding adverse effects, pain scores and satisfaction levels of the patients and surgeon. CONCLUSION: Compared to dexmedetomidine, at similar sedation levels, sedation provided by ketofol enables satisfactory analgesia. Moreover, ketofol has a more rapid onset of action and a shorter recovery period from anaesthesia without causing significant haemodynamic or respiratory adverse effects. PMID- 27366474 TI - The Effects of Different Anaesthetic Techniques on Surgical Stress Response During Inguinal Hernia Operations. AB - OBJECTIVE: The aim of this study is to compare the effects of 3 different kinds of anaesthesia on stress response induced by surgery. METHODS: Sixty patients aged between 25-70 American Society of Anesthesiologists (ASA) I-II group to undergo inguinal herniography were included in this study. Patients were randomly divided into 3 groups of 20. Group 1 received general anaesthesia with sevoflurane/air/remifentanil, patients in Group 2 received total intravenous anaesthesia (TIVA) with propofol/air/remifentanil and Group 3 received spinal anaesthesia induced by hyperbaric bupivacaine, adjoined by remifentanil sedation. Mean arterial pressure (MAP), heart rate and SpO2 values were recorded preoperatively, intraoperatively and postoperatively at certain periods. Cortisol, leptin and glucose levels were preoperatively detected. Intervals were as; 15 minutes prior to the induction of anaesthesia, at intraoperative first hour and at the postoperative third and twenty-forth hours. RESULTS: MAP and heart rate values were similar in the inhalational anaesthesia and TIVA groups but relatively higher in the spinal anaesthesia group. Blood glucose levels were elevated, insulin levels were decreased in all groups, at the intraoperative first hour. Biphasic variation in blood leptin levels was observed in all groups, as the levels were lower than the preoperative control values at the intraoperative first and postoperative third hours and significantly higher at the postoperative twenty-forth hour. There was a significant decrease in cortisol level percentage change in the TIVA group at the intraoperative 1st hour, increasing in the other groups. CONCLUSION: We concluded that TIVA supresses the stress response induced by surgery better by lowering cortisol levels, leading to a lower increase in blood glucose levels and a lower decrease in blood insulin levels when compared to others. Furthermore, leptin levels were increased at the postoperative twenty-forth hour. The lower increase at the postoperative twenty forth hour in the TIVA group can be correlated with the anaesthetic agent. PMID- 27366475 TI - Effects of Bowel Preparation and Fluid Restriction in Robot-Assisted Radical Prostatectomy Patients. AB - OBJECTIVE: In Robot-assisted radical prostatectomy (RARP) patients, preoperative bowel preparation and intraoperative fluid restriction may cause dehydration and electrolyte imbalance. In these patients, laboratory results that are considered "normal" in the pre-anaesthesia clinic may be misleading, and cardiac arrhythmia due to hypokalaemia and hypocalcaemia, as well as problems, such as prolonged non depolarising blockade and delayed recovery from anaesthesia, may be observed during anaesthesia practice. In this study, we aimed to determine these disturbances by comparing the preoperative (T1) laboratory values with those at the beginning of the operation (T2) and at the 6(th) hour of the operation (T3) and values at discharge. METHODS: This prospective study comprised 49 American Society of Anesthesiologists (ASA) I-II patients. Bowel preparation was made with a rectal enema (NaP) twice in 12 hours and with one single dose of oral laxative soda (NaP). During surgery, 1 mL kg(-1) h(-1) 0.09% NaCl and 1 mL kg(-1) h(-1) 6% HES 200/05 infusions were applied. RESULTS: The potassium level at T2 was significantly lower than at T1 and T3. The calcium levels at T2 and T3 were significantly lower than at T1, and the level at T3 was significantly lower than at T2. The creatinine level at T3 was significantly higher than at T1 and T2. CONCLUSION: Although there were no severe increases or decreases in laboratory test values due to bowel preparation and fluid restriction in RARP operations, which reflected on the clinical outcome in this ASA I-II patient group, these changes may be important in critically ill or ASA III-IV patients. PMID- 27366476 TI - Comparison of the Effects of Thiopental Sodium and Propofol on Haemodynamics, Awareness and Newborns During Caesarean Section Under General Anaesthesia. AB - OBJECTIVE: To compare the effects of propofol and thiopental on haemodynamics, awareness and newborns in pregnant women undergoing elective caesarean section. METHODS: Seventy pregnant women were assigned into two equal groups. For anaesthesia induction, 2 mg kg(-1) propofol (Group P) and 5 mg kg(-1) thiopental (Group T) were administered. Maternal haemodynamic parameters and bispectral index (BIS) values were recorded before induction, in 1-minute intervals within the first 10 minutes after induction and in 5-minute intervals thereafter, during skin incision, uterine incision, removal of infant, uterine sutures, skin sutures, eye opening and extubation in all cases. Cord blood gas analysis and 1- and 5-minute APGAR scores were recorded. In all cases, a keyword was spelled to ear during removal of the infant, and at the first postoperative hour, patients were questioned. Important time periods of surgery and anaesthesia and also the first postoperative hour haemodynamic values, pain scores, nausea and vomiting were noted. RESULTS: The demographic data were similar among cases. In Group T, systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and mean arterial pressure (MAP) at the first 2 minutes after induction and heart rate (HR) at almost all time points were significantly higher. BIS values from induction to the eighth minute and skin incision, uterine incision and removal of the infant were lower in Group P. No patient remembered the keyword spelled, while 4 patients reported dreaming during general anaesthesia. The effects of propofol and thiopental sodium on 1- and 5-minute APGAR scores, cord blood gas values and postoperative visual analogue scale (VAS) scores were similar. CONCLUSION: Propofol is a more appropriate anaesthetic agent than thiopental in anaesthesia for caesareans, since it provides better anaesthestic depth and more rapid recovery. PMID- 27366477 TI - What Do Current Information and Evidence Suggest to Us for Oxytocin Use During Caesarean Section? AB - Oxytocin is the first-line agent in the prevention and treatment of uterine atony and maintenance of uterine tone. Since there are several different practices related to the use of oxytocin during caesarean sections, we would like to address the latest information and evidence for rational oxytocin use. PMID- 27366478 TI - Acute Pancreatitis Due to Hypertriglyceridaemia in Pregnancy. AB - Acute pancreatitis due to hypertriglyceridaemia during pregnancy is a rare but severe clinical condition that may cause fatal results for both the mother and the foetus. Acute pancreatitis developed in a 37-year-old pregnant woman with familial hypertriglyceridaemia and diabetes mellitus in the 31(st) week of pregnancy. As intrauterine foetal death developed, the pregnancy of the patient was terminated. Additionally, insulin, octreotide and plasmapheresis with "double membrane filtration" were applied, and triglycerides rapidly decreased. After 24 hours, the level of triglycerides decreased from 9742 mg dL(-1) to 432 mg dL(-1). The patient was discharged from the intensive care unit at the end of 5 days and was discharged from the hospital after 32 days. The current article presents the successful treatment of severe hypertriglyceridaemia in a pregnant case. PMID- 27366479 TI - Atypical Presentation of Posterior Reversible Encephalopathy Syndrome in a Patient Diagnosed with Postpartum Gestational Hypertension. AB - Hypertensive disorders of pregnancy are a major cause of maternal mortality and morbidity. Preeclampsia and eclampsia are among the most common causes of posterior reversible encephalopathy syndrome (PRES). Clinically, PRES is characterised by visual disturbances, headache, nausea, change in mental status and seizure. Although treatment of the underlying cause provides clinical and radiological healing, a delay in the diagnosis and treatment can result in permanent brain damage and death. The exact incidence of new-onset postpartum hypertension is difficult to ascertain. Women with mild hypertension are usually asymptomatic; therefore, patients either can not be diagnosed or are diagnosed with late complications. With this case, we would like to present a patient who had no diagnosis of maternal hypertension or preeclampsia-eclampsia during pregnancy but, after a postpartum seizure, was diagnosed with PRES. PMID- 27366480 TI - Continuous Spinal Anaesthesia for Endovascular Repair of Abdominal Aortic Aneurysm in High-Risk Patient. AB - Endovascular aneurysm repair (EVAR) is increasingly being used in abdominal aortic aneurysm (AAA) treatment, as it is less invasive than open surgery. A wide range of anaesthetic types, such as general anaesthesia, neuroaxial blocks and local anaesthesia, have been shown to be appropriate for the EVAR procedure. In the continuous spinal anaesthesia (CSA) method, the local anaesthetic may be titrated through a catheter placed in the subarachnoid space, allowing better control of the anaesthetic level and a reduction in potential haemodynamic side effects. Our aim is to present CSA as a successful anaesthetic technique for EVAR in an AAA patient with severe co-existing diseases. PMID- 27366481 TI - A Case of Compartment Syndrome in the Hand Secondary to Intravenous Fluid Application. AB - Compartment syndrome of the extremities is a rare but potentially devastating condition. Anaesthetic and analgesic drugs used in the perioperative period may cause a delayed diagnosis by preventing the symptoms from appearing, and irreversible complications can occur. In this report, a case of compartment syndrome secondary to vascular access and its treatment in a morbidly obese patient who underwent abdominoplasty was presented. PMID- 27366482 TI - Intraoperative Ephedrine Allergy in a Patient Who Received Chemotherapy and Perioperative Hypersensitivity Reactions. AB - Anaesthesia represents a specific set-up in respect to pharmacology, and during this time, early hypersensitivity reactions or anaphylaxis may occur in patients who are exposed to a great number of foreign substances. Intravenous ephedrine (5 mg) was applied to a 37-year-old patient due to the development of intraoperative hypotension in a total abdominal hysterectomy operation. After application, hyperaemia was seen in the track of the intravenous catheter of that extremity. Approximately 15 minutes later, urticarial plaques were observed extensively in the abdomen and in both extremities. Methylprednisolone (100 mg+100 mg) and pheniramine (45.5 mg) were given with an increasing infusion rate of intravenous crystalloid. The patient was extubated without any problem and removed to the recovery unit for observation. After the total disappearance of lesions at postoperative 60 minutes and because of the stability of vital signs, the patient was removed to the service. In the follow-up of surgery, no complication developed, and the patient was discharged on postoperative day 2. PMID- 27366483 TI - A Case Report of Toxic Brain Syndrome Caused by Methyl Bromide. AB - Methyl bromide (CH3Br) is a halogenated aliphatic hydrocarbon that may cause acute and chronic toxicities. We describe a case of a 44-year-old male patient who developed toxic brain syndrome (TBS) and central nervous system (CNS) toxicity after exposure to CH3Br by inhalation. Toxicity began with progressive nervousness, dysarthria and coordination disorder. The complaints on admission to the hospital were speech defect, balance disorder, consciousness disorder and involuntary movements. The patient was treated symptomatically in the intensive care unit (ICU), and organic reasons were excluded. Findings in the magnetic resonance imaging were considered secondary demyelination related to systemic intoxication. Because of the CH3Br, alkylates the crucial sulfhydryl-containing enzymes, N-acetylcysteine was used as a source of sulfhydryl groups for the treatment of the patient. He was hospitalised for nearly 1.5 months in the ICU. PMID- 27366484 TI - Lateral Sagittal Infraclavicular Block Under Sedation in a Four-Year-Old Child. PMID- 27366485 TI - A New Threat in Anaesthesia-Bonzai. PMID- 27366486 TI - Comparison of Patient Costs in Internal Medicine and Anaesthesiology Intensive Care Units in a Tertiary University Hospital. AB - OBJECTIVE: The allocation of the Gross Domestic Product (GDP) to health is limited, therefore it has made a need for professional management of health business. Hospital managers as well as employees are required to have sufficient knowledge about the hospital costs. Hospital facilities like intensive care units that require specialization and advanced technology have an important part in costs. For this purpose, cost analysis studies should be done in the general health business and special units separately. METHODS: In this study we aimed to compare the costs of anaesthesiology and internal medicine intensive care units (ICU) roughly. RESULTS: After approval of this study by Gazi University Faculty of Medicine Ethics Committee, the costs of 855 patients that were hospitalized, examined and treated for at least 24 hours in internal medicine and anaesthesiology ICUs between January 2012-August 2013 (20 months period) were taken and analyzed from chief staff of the Department of Information Technology, Gazi University Hospital. CONCLUSION: At the end of the study, we observed clear differences between internal medicine and anaesthesiology ICUs arising from transactions and patient characteristics of units. We stated that these differences should be considered by Social Security Institution (SSI) for the reimbursement of the services. Further, we revealed that SSI payments do not meet the intensive care expenditure. PMID- 27366487 TI - Radiological Evaluation of the Line Between the Crista Iliaca (Tuffier's line) in Elderly Patients. AB - OBJECTIVE: Tuffier's line is defined as the line connecting the highest points of both iliac crests, which generally passes through either the body of the fourth lumbar vertebra or the intervertebral space between fourth and fifth vertebrae. In this study, we assessed the radiological correlation of the level of Tuffier's line with changes in age and sex. METHODS: In this study, antero-posterior pelvic X-rays of 590 patients aged 18 and older were retrospectively analyzed. It is revealed that Tuffier's line crosses the vertebral column at one of three levels, which are the L4 vertebral body, L4-L5 vertebral interspace and L5 vertebral body. Patients' sex, age and vertebral level of the Tuffier's line were recorded. Data was analyzed using the chi-square test. RESULTS: The assessment of the X rays of 317 female patients showed that Tuffier's Line passes through the L4 vertebral body in 115 (37.8%), through the L4-L5 intervertebral space in 126 (40%) and through the L5 vertebral body in 76 (22.2%) patients. A Tuffier's line passing through the level of the L5 vertebral body was found to be statistically significant in female patients (p=0.00). No significant relevance was found between male gender and the level of Tuffier's line in 273 male patients. It is found that the height of the vertebral levels that Tuffier's line crosses does not correlate with mean age of the groups (p=0.939). CONCLUSION: It should be considered that Tuffier's line can cross at vertebral levels other than anticipated. The level of Tuffier's line should be precisely determined with supplementary radiological methods, such as AP pelvic X-ray in addition to physical examination, to reduce the complications in association with regional anaeshesia and to achieve sensorial block levels sufficient to sustain a comfortable surgery, particularly in female patients who carry higher cardiac and respiratory risks. PMID- 27366488 TI - Investigation of Effects of Epidural Anaesthesia Combined with General Anaesthesia on the Stress Response in Patients Undergoing Hip and Knee Arthroplasty. AB - OBJECTIVE: To investigate the effects of general anaesthesia and general+epidural anaesthesia on the stress response which was evaluated with the adrenocorticotrophic hormone (ACTH), cortisol, insulin, and glucose levels and the haemodynamic parameters. METHODS: Forty two, American Society of Anesthesiologists physiologic status I-II, patients undergoing hip and knee arthroplasty were randomized into two groups; general anaesthesia (Group G) and general anaesthesia+epidural anaesthesia (Group E). Epidural anaesthesia: patients in Group E received epidural anaesthesia with 0.5% bupivacaine, a lumbar epidural catheter was placed and after achieving sensorial block at T10 dermatome, general anaesthesia was commenced. General anaesthesia was standardized in both groups. Further, plasma ACTH, cortisol, insulin and glucose levels were determined at preoperative=t1, after the surgical incision=t2, postoperative 2(nd) hour=t3 and postoperative 24(th) hour=t4. Perioperative heart rate, blood pressures, pain scores and morphine consumption were also determined. RESULTS: ACTH levels were higher in Group G than Group E [Group G, t2: 71.4+/ 39.9 pg mL(-1), t3: 578.6+/-566.1 pg mL(-1), Group E, t2: 20.2+/-16.2 pg mL(-1), t3: 56.3+/-73.6 pg mL(-1) (p<0.001)]. Cortisol, was higher in Group G compared with Group E [Group G, t3: 33.4+/-13.1 MUg dL(-1), t4: 34.1+/-22.5 MUg dL(-1), Group E, t3: 19.1+/-10.3 MUg dL(-1), t4: 21.3+/-8.1 MUg dL(-1) (p=0.001 and p=0.002)]. The insulin levels were higher compared with the baseline values at t3, and glucose was higher at t3 and t4 in both groups. Haemodynamic parameters were stable in Group E, and pain scores and morphine consumption were higher in Group G than in Group E. CONCLUSION: Our results suggest that epidural anaesthesia combined with general anaesthesia suppressed the stress response, which was evaluated with ACTH, cortisol levels and haemodynamic parameters; however, this method was ineffective to attenuate the increase in glucose and insulin levels. PMID- 27366489 TI - Comparison of Intraoperative and Postoperative Effects of Lateral Epidural and Midline Epidural Anaesthesia in Patients Undergoing Unilateral Lower Extremity Operation. AB - OBJECTIVE: We aimed to compare lateral and midline epidural anaesthesia using a levobupivacaine-fentanyl combination in patients undergoing unilateral lower extremity operation for anaesthetic effects and postoperative complications. METHODS: The study included 40 American Society of Anesthesiologists (ASA) I-II group patients. At the L4-5 space, an epidural catheter was placed in patients in Group 1 by directing the tip of the needle at a 45-degree angle to the operation side and in Group 2 with the needle tip in the cephalad direction. Patients in both groups were administered a combination of 10 mL 0.5% levobupivacaine and 50 MUg fentanyl via the epidural catheter. Sensorial and motor block levels during the perioperative and postoperative periods and postoperative complications were recorded. RESULTS: The maximum level of sensory block on the operated side was found to be at the T10 (T8-T10) level in both groups, while the level of sensory block on the non-operated side was at the L2 (L3-T10) level in Group 1, and at the T10 (T8-T10) level in Group 2 (p=0.000). The motor block was more intense on the non-operated side in Group 2 than in Group 1. The postoperative motor block ended earlier in Group 1. The incidence of complication development was similar between the groups. CONCLUSION: With a shorter lasting and lower level sensorial and motor block, lateral epidural anaesthesia may be a more advantageous method than midline epidural anaesthesia. PMID- 27366490 TI - Effects of Systemic Disorders on Postoperative Complications After Simultaneous Bilateral Total Knee Replacement. AB - OBJECTIVE: The aim of the present study was to retrospectively evaluate the association between accompanying systemic disorders and major complications developing in the early postoperative period in patients who underwent simultaneous bilateral total knee arthroplasty with combined spinal and epidural anaesthesia. METHODS: In the present study, the medical records of a total of 456 patients were analyzed. Preoperative data, including the American Society of Anesthesiologists physical status and presence of coronary artery disease (CAD), chronic pulmonary disease, diabetes mellitus (DM), hypertension and renal insufficiency were recorded. Furthermore, the data related to major complications, such as cardiac complications, respiratory complications, acute myocardial infarction (AMI), thromboembolism, cerebrovascular accident (CVA), confusion, acute renal failure (ARF), shock and cardiopulmonary arrest were recorded. RESULTS: We found that the frequency of complications markedly increased in the presence of concurrent DM and hypertension, or DM, hypertension and CAD, or DM and CAD. Further, 0.2% of the patients developed AMI, 3.3% developed cardiac complications, 2.2% developed respiratory complications, 0.9% developed thromboembolism, 0.2% developed CVA, 2% developed confusion and 0.4% developed cardiac arrest and shock in the first week after the operation. The frequency of cardiac and pulmonary complications and confusion was higher in patients aged above 65 years compared to patients below 65 years. CONCLUSION: We observed that the frequency of cardiac and pulmonary complications and confusion in the early postoperative period was markedly higher in patients aged above 65 years and in patients with concurrent DM and cardiovascular comorbidities. PMID- 27366491 TI - A Comparative Study of the Efficacy of IV Dexketoprofen, Lornoxicam, and Diclophenac Sodium on Postoperative Analgesia and Tramadol Consumption in Patients Receiving Patient-Controlled Tramadol. AB - OBJECTIVE: This study was designed to compare the effects of dexketoprofen, lornoxicam, and diclophenac sodium on postoperative analgesia and tramadol consumption in patients receiving postoperative patient-controlled tramadol after a major abdominal surgery. METHODS: Eighty patients were randomized to receive one of the four study drugs. Patients in group dexketoprofen (DT) received IV 50 mg dexketoprofen, group lornoxicam (LR) received IV 8 mg lornoxicam, group diclophenac sodium (DS) received 75 mg IV diclophenac sodium and group saline (S) received 0.9% saline in 2 mL syringes, 20 min before the end of anaesthesia. A standardized (1 mg kg(-1)) dose of tramadol was routinely administered to all patients as the loading dose at the end of surgery. Postoperatively, whenever patients requested, they were allowed to use a tramadol patient-controlled analgesia device giving a bolus dose (0.2 mg kg(-1)) of tramadol. Pain, discomfort, and sedation scores, cumulative tramadol consumption, supplemental meperidine requirement, and side effects were recorded. RESULTS: Visual rating scale and patient discomfort scores were significantly lower in DT, LR and DS groups compared to those in in group S (p<0.001). Cumulative tramadol consumption was significantly lower in non-steroidal anti-inflammatory drug (NSAID)-treated groups at each study period after the second postoperative hour than in group S (p<0.001). Supplemental meperidine requirement was significantly higher in group S at each study period after postoperative 30 min than in NSAID-treated groups (p<0.01). CONCLUSION: After major abdominal surgery, adding IV diclophenac, lornoxicam or dexketoprofen to patient-controlled tramadol resulted in lower pain scores, smaller tramadol consumption, less rescue supplemental analgesic requirement, and fewer side effects compared with the tramadol alone group. PMID- 27366492 TI - Comparison of the Macintosh and Airtraq Laryngoscopes in Endotracheal Intubation Success. AB - OBJECTIVE: Endotracheal intubation of patients is an effective method for controlling airway and breathing. However, laryngoscopy and endotracheal intubation is not easy in every case. There is a recent abundance of equipment used for controlling ventilation and intubation. Airtraq is one of those equipments. In this study, our main objective is to compare the success rates of the Airtraq and Macintosh (direct and classic) laryngoscopes in endotracheal intubation. METHODS: In this single-center, prospective, randomized, clinical study was performed on 80 patients who were operated under general anesthesia, ASA I-II, 18-65 years old. Patients were intubated using two different endotracheal intubation tools. Group A was intubated using the Macintosh (direct and classic) laryngoscope, meanwhile Group B was intubated using the Airtraq laryngoscope. Patients' snoring complaints, modified Mallampati scores, sternomental distances, thyromental distances, interincisor distance measurements and Cormack-Lehane (C-L) laryngoscopic classification, upper lip bite test results, intubation time, number of intubation attempts, maneuvers and techniques used for facilitating intubation and complications arising from intubation were recorded. RESULTS: There was a statistically significant difference between the groups in terms of C-L scores (p=0.041). In all, 8 patients in the Macintosh group, and 2 patients in the Airtraq group were C-L grade III. In intubation of the Airtraq group, only 3 patients required facilitating techniques, meanwhile in intubation of the Macintosh group 15 patients we had to use one or more facilitating maneuver. The rate of Mallampati scoring "difficult" was 4/6 in the Macintosh and 2/11 in Airtraq laryngoscopy groups (p=0.553). CONCLUSION: In cases with seemingly difficult intubations, we believe the Airtraq laryngoscope has an advantage over the Macintosh laryngoscope, owing to its better view of the oropharyngeal and glottic areas in addition to facilitating intubation in patients with limited head extension. PMID- 27366494 TI - Unilateral Horner Syndrome Following Epidural Anaesthesia in a Morbidly Obese Parturient. AB - Horner's syndrome is rarely observed in epidural anaesthesia; it is characterized by ptosis and enophthalmos on the affected side; miosis, anisocoria, and conjunctival hyperemia in the affected eye and anhydrosis, flushing on the affected side of the face. It is usually a complication spontaneously resolved without permanent neurological deficits. Intraoral anaesthesia, stellate, cervical and brachial plexus block, thoracic, lumbar and caudal epidural anaesthesia and intrapleural analgesia are the main causes associated with Horner's syndrome in anaesthesia. Among the other causes of Horner's syndrome are head and neck surgery, trauma and puncture of the internal jugular vein. We aimed to present a case with unilateral Horner's syndrome, which appeared in the morbidly obese parturient after lumbar epidural anaesthesia. PMID- 27366493 TI - Current Approaches in Hip and Knee Arthroplasty Anaesthesia. AB - Risk assesment, preoperative drug regulation, the anesthesia and analgesia techniques are very important and the effectivity on success of surgery is great. So, these topics in arthroplasty were reviewed under current knowledge. PMID- 27366495 TI - Late Local Anaesthetic Toxicity After Infraclavicular Block Procedure. AB - Local anaesthetic (LA) toxicity is the most fatal complication of peripheral nerve block techniques. Accidental intravascular application or use of doses above the safety range are the most common cause of toxicity. Bupivacaine is a long-acting LA frequently used for long procedures or those associated with significant post-procedural pain. Fatal central nervous system and cardiovascular system toxicity are described. In this paper, we reported a young patient who showed LA toxicity symptoms 7 h after an infraclavicular peripheral block. PMID- 27366496 TI - Unanticipated Disturbance in Somatosensory Evoked Potentials in a Patient in Park Bench Position. AB - Perioperative neuropathy is a known complication of malpositioning during anaesthesia. Somatosensory evoked potentials are used for detecting such a complication in selected surgeries. Most reports of intraoperative nerve injuries due to malpositioning are limited to injuries to the peripheral nervous system, and there have been no previously reported cases of somatosensory evoked potential monitoring disturbance attributable to position-related cerebral ischemia in the park-bench position. We present the case of a patient with glioblastoma in the park-bench position whose somatosensory evoked potential waveforms disappeared after head and neck repositioning. A prompt diagnosis of this complication and elimination of the underlying cause led to the return of somatosensory evoked potential waveforms, and there was no relevant neurologic deficit at the end of the surgery. PMID- 27366497 TI - Anaesthetic Management of a Patient with Synchronous Kartagener Syndrome and Biliary Atresia. AB - Kartagener syndrome is an autosomal recessive disorder characterized by primary ciliary dyskinesia accompanied by sinusitis, bronchiectasis, and situs inversus. Synchronous extrahepatic biliary atresia and Kartagener syndrome are very rare. During the preoperative preparation of patients with Kartagener syndrome, special attention is required for the respiratory and cardiovascular system. It is important to provide suitable anaesthetic management to avoid problems because of ciliary dysfunction in the perioperative period. Further, maintaining an effective pain control with regional anaesthetic methods reduces the risk of pulmonary complications. Infants with biliary atresia operated earlier have a higher chance of survival. Hepatic dysfunction and decrease in plasma proteins are important for the kinetics of drugs. In this presentation, the anaesthetic management of patients with synchronous Kartagener syndrome and biliary atresia, both of which are rare diseases, is evaluated. PMID- 27366498 TI - Delayed Post-Traumatic Anisocoria. AB - Post-traumatic carotid artery dissection is one of the major causes of ischemic stroke in young patients; its diagnosis remains a challenge for clinicians because of its variable clinical presentation. An otherwise healthy 37-year-old man was referred to the intensive care unit of our faculty for the management of multiple trauma because of a car accident. At 11 days from admission, his doctor noticed the advent of anisocoria. A prompt treatment was instituted with anti platelet and-coagulant agents. The patient had a complete resolution of symptoms. The prognosis was good, and the patient achieved a complete clinical recovery. He was discharged without any sequelae. PMID- 27366499 TI - Absence of the Right Internal Jugular Vein During Ultrasound-Guided Cannulation. AB - Cannulation of the internal jugular vein (IJV) may be diffucult because of anatomical variations. A 66-year-old female patient, who was in the intensive care unit, underwent ultrasound-guided cannulation of the right IJV. The right IJV could not be visualized by ultrasonography despite positional changes of the patient and Valsalva maneuvre. The left IJV was easily determined by ultrasonography and cannulated. Although the landmark technique may be sufficient for most of the central vein cannulations, the rate of anatomical variations and related complications is quite high. We point out that even if ultrasound cannot be used in real-time, the ultrasonographic confirmation during the pre-insertion period may be crucial for successful central vein cannulation. PMID- 27366500 TI - Effects of Hemodilution and Transfusion on Acute Renal Injury and Neutrophil Gelatinase-Associated Lipocalin. PMID- 27366501 TI - Effects of Hemodilution and Transfusion on Acute Renal Injury and Neutrophil Gelatinase-Associated Lipocalin-Author's Reply. PMID- 27366502 TI - Assessment of Some Public Hospitals in Turkey Regarding Anaesthetist, Anaesthesia and Intensive Care Equipment. AB - OBJECTIVE: Every year, 230 million patients undergo major general surgery with anaesthesia worldwide, and 7 million resulted with major complications. Monitorisation and equipment has a great role in increasing patient safety and safe surgery during anaesthesia. METHODS: Turkey is divided into 12 Eurostut-NUTS regions and 26 subregions statistically. Totally, 303 hospitals that are included in these regions were enrolled in this descriptive trial. The hospitals were contacted by telephone between October 2012 and August 2013. Data collecting forms were e-mailed to any of the anaesthetists or anaesthesia technicians of the hospital and they were requested to fill the forms and forward them to one of the investigators. RESULTS: Data were obtained from 221 of 303 hospitals (73%). Twenty-three hospitals were tertiary (university and education and research), 21 were city and 177 were county hospitals. No anaesthetist, operating rooms or intensive care units were available in 114 of the county hospitals. Anaesthetists were responsible for 61% of these active working theatres. Electrocardiogram, heart rate, non-invasive blood pressure and saturation could be monitored in 97% of them. End-tidal carbon dioxide could be monitored in 91% of at least one operating room in these hospitals. However, if the subject became to end-tidal carbon dioxide monitoring in every room, this ratio decreased to 63%. Defibrillators were absent in 6% of these rooms. Adult intensive care units were available in 33% of the hospitals and paediatric intensive care units were available in 32.4%; the responsibility of these intensive care units were carried out by anaesthetists at a 91.4% ratio. End-tidal carbon dioxide could be monitored in 54% of these units; invasive monitorisation could be applied in 68.4% if needed. CONCLUSION: It was observed that hospitals have different standards according to their infrastructures of anaesthesia and intensive care unit equipment. We think that the elimination of these differences is an important step with respect to increasing patient safety and enhancement of the service quality in hospitals. PMID- 27366503 TI - Cardioprotective Effects of Remifentanil in a Sympathetic Hyperactivity Model in Rabbits. AB - OBJECTIVE: In this study, the antiarrhythmic and anti-ischemic effects of a 6 MUg kg(-1) min(-1) infusion dose of remifentanil are investigated in a central sympathetic hyperactivity model in rabbits. METHODS: In this study, 18 New Zealand rabbits were used. The subjects were randomly divided into three groups (n=6) and received 10 MUmol L(-1) glutamate intracerebroventricularly to provide the central sympathetic hyperactivity. In group 1, 10 MUmol L(-1) glutamate was used; in group 2, 1 h before L-glutamate injection, 40 mg kg(-1) N (omega)-nitro L-arginine methyl ester was intravenously (iv) administered; and in group 3, also 1 h before L-glutamate injection, 40 mg kg(-1) N (omega)-nitro-L-arginine methyl ester was iv administered. A 6 MUg kg(-1) min(-1) dose of remifentanil infusion was administered 5 min before L-glutamate injection. Heart rate, systolic arterial pressure and mean arterial pressure were measured and recorded. Within 15 min of the intracerebroventricular L-glutamate injection, premature ventricular complexes, bigeminy ventricular arrhythmia, ventricular tachycardia, ST-segment shift and T-wave inversions were recorded. RESULTS: When incidences of heart rate, rate pressure product, premature ventricular complexes and bigeminy ventricular arrhythmia were compared between groups, significant differences were not determined. Mean arterial pressure was more significantly increased in group 2 than in the other groups (p<0.05). Ventricular tachycardia, ST-segment shift and T-wave inversions were significantly lower in group 3 than in groups 1 and 2 (p<0.05). CONCLUSION: Remifentanil (6 MUg kg(-1) min(-1) for 5 min of infusion) prevented life-threatening ventricular tachycardia and electrocardiographic signs of myocardial ischemia in a model of arrhythmia resulting from the association of central sympathetic overactivity. PMID- 27366504 TI - The Incidence of Delirium at the Postoperative Intensive Care Unit in Adult Patients. AB - OBJECTIVE: In this study, we aimed to determine the risk factors and the incidence of delirium in patients who were followed postoperatively in our surgical intensive care unit for 24 h using the confusion assessment method (CAM). METHODS: After obtaining approval from the ethics committee, 250 patients were included in the study. Patients who were operated under general anaesthesia or regional anaesthesia and followed in the surgical intensive care unit were evaluated by the Ramsay Sedation Scale on the first postoperative day. CAM was applied to the patients who had a Ramsey Sedation Score of <=4. Patients' age, gender, American Society of Anesthesiologists (ASA) scores, preoperative risk factors, type of anaesthesia, operation time, intra-operative procedures, pain scores evaluated by the visual analogue scale (VAS) and postoperative analgesia methods were recorded. RESULTS: The incidence of delirium was found to be 18.4%. The average age of patients who developed delirium was greater than the others (68.8+/-12.7 and 57.6+/-12, p=0.001, respectively). It was observed that a one unit increase in the ASA score resulted in a 3.3-fold increase in the risk of delirium. The incidence of delirium in patients undergoing regional anaesthesia was 34.6%, whereas it was 16.5% in patients receiving general anaesthesia (p=0.024). The existence of preoperative diabetes mellitus (DM) and chronic obstructive pulmonary disease (COPD) was shown to improve the development of delirium (p<0.05). Delirium incidence was significantly higher in patients who were administered meperidine for postoperative analgesia (p=0.013). The VAS scores of patients who developed delirium were found to be significantly higher (p=0.006). CONCLUSION: As a result, we found that older age, high ASA score, preoperative DM and COPD are important risk factors for the development of delirium. Regional anaesthesia, high postoperative pain scores and meperidine use were observed to be associated with the development of delirium. In the postoperative period, addition of CAM, a simple measurement technique, to the daily follow-up forms can provide the early recognition of delirium, which is often underdiagnosed. We think that identification and prevention of effective risk factors have the primary importance for postoperative delirium. PMID- 27366505 TI - Spectrum and Prevalence of Thyroid Disorders in Patients Admitted to the Anaesthesiology Outpatient Clinic for Surgery. AB - OBJECTIVE: An anaesthetic approach and surgery are important treatment strategies in patients with thyroid dysfunction due to potential complications. We investigated the prevalence of thyroid disorders, the significance of thyroid function tests (TFTs) with respect to anaesthesia in the preoperative period and the need for routine examinations. METHODS: A total of 10,600 patients who were admitted to the anaesthesiology outpatient clinic for surgery were retrospectively screened and enrolled between 2011 and 2013. Evident hypothyroidism was defined as free tetra-iodothyronine (fT4) <0.7 ng dL(-1) and thyroid-stimulating hormone (TSH) >4 mIU mL(-1), and subclinical hypothyroidism was defined as TSH >4 mIU mL(-1) with normal free hormone levels. Evident hyperthyroidism was defined as fT4 >1.7 ng dL(-1) and TSH <0.1 mIU mL(-1), and subclinical hyperthyroidism was defined as TSH <0.1 mIU mL(-1) with normal free hormone levels. Statistical analysis was conducted using the Statistical Package for the Social Sciences (SPSS) version 17.0. Independent samples t-test and one way analysis of variance were used to compare the difference between groups. RESULTS: Of the participants, 8.5% were found to have hypothyroidism, 2.5% had hyperthyroidism, 3.5% received treatment and 2.5% had their treatment postponed. The likelihood of hypothyroidism was greater among females, and no difference was found between genders with respect to hyperthyroidism. CONCLUSION: We believe that TFTs are important because of regional factors. However, given the high cost of TFTs and because thyroid dysfunction risk increases with age, we concluded that routine TFTs in young patients with normal physical examination findings are not mandatory. PMID- 27366506 TI - Comparison and Evaluation of the Effects of Administration of Postoperative Non Invasive Mechanical Ventilation Methods (CPAP and BIPAP) on Respiratory Mechanics and Gas Exchange in Patients Undergoing Abdominal Surgery. AB - OBJECTIVE: The aim of our study is to investigate the effect of two different methods of continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BIPAP) and oxygen support under spontaneous ventilation on respiration mechanics, gas exchange, dry mouth and face mask lesion during an early postoperative period in patients undergoing upper abdominal surgery. METHODS: Eighty patients undergoing elective abdominal surgery with laparotomy, between the age of 25 and 75 years and American Society of Anesthesiologists Physical Status score (ASA) II-III with chronic obstructive pulmonary disease (COPD) diagnosis were included to the study. Subjects were randomly allocated in to four groups. During the first postoperative hour, the first group received BIPAP, second group received high-flow CPAP, third group received low-flow CPAP and fourth group received deep breathing exercises, respiratory physiotherapy and O2 therapy. Preoperative, postoperative before and after treatment PaO2, PaCO2, SpO2, tidal volume (TV), respiratory rate (RR) levels were recorded. Subjects with dry mouth or face mask lesion were recorded. RESULTS: In all groups, PaO2 and TV measurements were higher at the postoperative first hour than the postoperative zero hour. We found that low-flow CPAP increased PaO2 and SpO2 values more, and TV levels were higher in the postoperative period than the preoperative period. PaCO2 levels were elevated at the zero hour postoperatively and at the end of the first hour; they decreased approximately to preoperative values, except in the fourth group. CONCLUSION: Administration of prophylactic respiratory support can prevent the deterioration of pulmonary functions and hypoxia in patients with COPD undergoing upper abdominal surgery. In addition, we found that low-flow CPAP had better effects on PaO2, SpO2, TV compared to other techniques. PMID- 27366507 TI - Turkish Anaesthesiologist's Experiences of Anaesthetic Management of Patients with Obstructive Sleep Apnea (OSA). AB - OBJECTIVE: Obstructive sleep apnea (OSA) is an important health problem that is increasing with the increase in the incidence of obesity. For patients with OSA, it is reported that preoperative OSA diagnosis is made in only 10%-20% of the patients. Therefore, it gains importance that these patients are diagnosed in the preoperative period. The aim of this study is to analyze with a survey the experiences of anaesthesia experts working in Turkey about the diagnosis of patients with OSA, anaesthetic methods and postoperative care. METHODS: The study was completed with an online survey form distributed via email. Survey participants were sent an email, and those experts who wished to participate clicked on the link, answered the questions and returned the survey via email. RESULTS: A total of 134 anaesthesia experts participated in this study. While 97% of the participating anaesthetists considered diagnosis of patients with OSA to be important, only 53% trusted themselves to recognize this patient group. Of the total number of participants. 43% did not know the STOP-BANG test used in the preoperative period to diagnose patients with OSA. The percentage who thought that patients with OSA would increase the incidence of difficult intubation was 84%. In the intraoperative period, the percentage who chose inhalation anaesthetics was 35%, whereas the rate of those who chose total intravenous anesthesia (TIVA) was 48%. CONCLUSION: This study indicates that the medical knowledge of Turkish anaesthetists on the topic of OSA requires updating. In addition, we believe a practical guide to standardize the diagnosis and preoperative/perioperative management of patients with OSA should be prepared for Turkish anaesthetists. PMID- 27366508 TI - Does Video Laryngoscopy Offer Advantages over Direct Laryngoscopy during Cardiopulmonary Resuscitation? AB - OBJECTIVE: Interruption of chest compressions should be minimized because of its negative effects on survival. This randomized, controlled, cross-over study aimed to analyze the effectiveness of Macintosh, Miller, McCoy and McGrath laryngoscopes during with or without chest compressions in the scope of a simulated cardiopulmonary resuscitation scenario. METHODS: The time required for successful tracheal intubation, number of attempts, dental trauma severity and the need for optimization manoeuvres were recorded during cardiopulmonary resuscitation with and without chest compressions. The experience with computer games during the last 10 years were asked to the participants and recorded. RESULTS: McCoy laryngoscope yielded the shortest time for successful tracheal intubation both in the presence of and without chest compressions. During the use of McCoy laryngoscopes, fewer tracheal intubation attempts, lower incidence of dental trauma and lower visual analogue scale scores on the ease of intubation were recorded. Participants who are experienced computer game players using Macintosh, McCoy and McGrath achieved successful tracheal intubation in a significantly shorter time during resuscitation without chest compressions. Dental trauma incidence and number of tracheal intubation attempts did not show any significant difference between the four laryngoscopes being related to the rate of playing computer games. CONCLUSION: McGrath video laryngoscopes do not appear to have advantages over direct laryngoscopes for securing a smooth and successful tracheal intubation during rhythmic chest compressions. We believe that as McCoy laryngoscope provided tracheal intubation in a shorter time and with fewer attempts, this laryngoscope may increase the success rate of resuscitation. PMID- 27366509 TI - Vitamin D and Anaesthesia. AB - Vitamin D is a vitamin not only associated with calcium-phosphorus metabolism but also affects many organ systems. Because of its effect on the immune system in recent years, it has attracted much attention. Vitamin D deficiency is a clinical condition that can be widely observed in the society. Thus, patients with vitamin D deficiency are often seen in anaesthesia practice. In the absence of vitamin D, prolongation of intensive care unit stay, increase in mortality and morbidity and also association of chronic diseases further increase the importance of vitamin D deficiency. The results obtained from studies have led to the question of whether poor surgical outcome is associated with vitamin D deficiency. We assessed the vitamin D deficiency and its negative consequences for the anaesthesiologist. PMID- 27366510 TI - Intraoperative 16-Channel Electroencephalography and Bilateral Near Infrared Spectroscopy Monitorization in Aortic Surgery. AB - Transient neurologic dysfunction is common after aortic surgery. Major causes of postoperative complications followed by cardiac surgery are due to hypoperfusion states such as selective cerebral perfusion, embolic debris during cardiopulmonary bypass and ulcerated plaque emboli originated from carotid arteries. Neurologic complications prolong periods of intensive care unit and hospital stay, worsens quality of life and unfortunately they are an important cause of morbidity. Anaesthesia during a carotid and aortic surgery constitutes of providing adequate brain perfusion pressure, attenuating cerebral metabolism by anaesthetic agents and monitoring the cerebral metabolic supply and demand relationship during the intraoperative period. We present a monitoring approach with an intraoperative 16-channel electroencephalography and bilateral near infrared spectroscopy during redo aneurysm of the sinus of Valsalva surgery. PMID- 27366511 TI - Popliteal Sciatic Nerve Block in a Pregnant Patient in the Last Trimester. AB - Although regional anaesthesia is a commonly preferred anaesthesia technique for pregnant patients undergoing non-obstetric surgery, peripheral nerve blocks are relatively less administered. The use of popliteal sciatic nerve block for foot ankle surgery has been presented for a nulliparous parturient at 32 weeks of gestation scheduled to undergo surgical exploration of an arterial pseudoaneurysm on her right plantar surface due to a penetrating stab injury. Since surgery did not require pneumatic tourniquet, the sciatic nerve was blocked via the popliteal approach with a single shot injection of 30 mL of 0.375% levobupivacaine. The operation and the anaesthesia course were uneventful. In conclusion, popliteal sciatic nerve block was successful and uneventful for a short foot surgery not requiring tourniquet application in a parturient in the last trimester. PMID- 27366512 TI - Breakage of an Epidural Catheter Inserted for Labor Analgesia. AB - The breakage of an epidural catheter, which is usually not noticed, is a rare but important complication encountered while inserting or removing the catheter during epidural blockade. While the epidural catheter was being inserted for labor analgesia, despite no problem being encountered in advancing the catheter, it was drawn back to verify the location; it was observed that 2 cm of the distal end of the catheter was missing. A neurosurgical consultation was requested; it was reported that the broken piece would not create any problems and reintervention could be performed for labor analgesia. An epidural catheter was reinserted and was used for analgesia without any problem until delivery. Although nine months have passed, no problem was defined by the patient. If epidural catheter has to be removed while the Tuohy needle is still in place, we recommend that they should be removed together to minimize the risk of a possible breakage. We think that the decision for surgery and imaging can be performed based on the individual patient's clinical picture. PMID- 27366513 TI - Single Shot Spinal Anaesthesia for Caesarean Delivery of Two Achondroplasic Parturients. AB - Because of structural defects in achondroplasia, as one of the dwarfism types, the choice of an anaesthetic technique and management for caesarean delivery presents a challenge. We aimed to discuss our successful single-shot spinal anaesthesia approach for caesarean section for one urgent and one elective achondroplasic parturient based on the literature. PMID- 27366514 TI - Successful Management of Aluminium Phosphide Poisoning Resulting in Cardiac Arrest. AB - Aluminum phosphide has high toxicity when it is ingested, and in case of contact with moisture, phosphine gas is released. Aluminum phosphide poisoning causes metabolic acidosis, arrhythmia, acute respiratory distress syndrome and shock, and there is no specific antidote. A 17-year-old male patient was referred to our hospital because of aluminum phosphide poisoning with 1500 mg of aluminum phosphide tablets. The patient's consciousness was clear but he was somnolent. Vital parameters were as follows: blood pressure: 85/56 mmHg, pulse: 88 beats/min, SpO2: 94%, temperature: 36.4 degrees C. Because of hypotension, noradrenaline and dopamine infusions were started. The patient was intubated because of respiratory distress and loss of consciousness. Severe metabolic acidosis was determined in the arterial blood gas, and metabolic acidosis was corrected by sodium bicarbonate treatment. In addition to supportive therapy of the poisoning, haemodialysis was performed. Cardiac arrest occurred during follow ups in the intensive care unit, and sinus rhythm was achieved after 10 min of cardiopulmonary resuscitation. The patient was discharged after three sessions of haemodialysis on the ninth day. As a result, haemodialysis contributed to symptomatic treatment of aluminum phosphide poisoning in this case report. PMID- 27366515 TI - Treatment of Posterior Reversible Encephalopathy Syndrome that Occurred in a Patient with Systemic Lupus Erythematosus by Plasmapheresis. AB - Posterior reversible encephalopathy syndrome is characterized by visual and mental disturbances, nausea and vomiting and generalized or focal convulsions and often represents itself with parietal and occipital oedema formation. We want to report the treatment of posterior reversible encephalopathy syndrome with plasmapheresis, which developed in a 35-year-old woman with systemic lupus erythematosus diagnosed by renal biopsy 3 years ago. She has been followed up in the intensive care unit three times. However, she had been transferred to the nephrology department of our university hospital because of her uncontrolled blood pressure. Oral antihypertensive therapy, corticosteroid 500 mg 1 * 1 and cyclophosphamide were started for the activation of lupus. After the detection of low complement levels, systemic lupus erythematosus activation was suspected. She developed mental deterioration after her first plasmapheresis treatment and was then consulted by the neurology and intensive care unit doctors. Diffusion cranial magnetic resonance imaging was found compatible with posterior reversible encephalopathy syndrome. The patient was transferred to our intensive care unit. The patient gained consciousness after her second plasmapheresis. After 5 days of follow-up in our intensive care unit and after significant regression was observed in the magnetic resonance imaging analysis, the patient was transferred to the nephrology service conscious, cooperated and orientated. At the nephrology service, after a total of 13 times of plasmapheresis, complement levels were increased and she was discharged with corticosteroid therapy. Posterior reversible encephalopathy syndrome can be observed in patients with systemic lupus erythematosus and intensive care unit treatment may be required. To control the hypertension, plasmapheresis should be kept in mind in addition to the multiple antihypertensive therapy in these patients. PMID- 27366516 TI - Anaesthesia Management of a Patient with Undiagnosed Hypertrophic Cardiomyopathy. PMID- 27366517 TI - Management of Severe Paroxysmal Sympathetic Hyperactivity Following Hypoxic Brain Injury. PMID- 27366518 TI - Comparison of I-gel with Classic Laryngeal Mask Airway Regarding the Ease of Use and Clinical Performance. AB - OBJECTIVE: I-gel is a new supraglottic airway device without an inflatable cuff. We aimed to compare I-gel and the classic laryngeal mask airway (LMA) regarding the ease of use and clinical performance in Turkish population. METHODS: Fifty American Society of Anesthesiologists (ASA) I-II patients were randomly allocated into two groups: Group I-gel and Group LMA. Insertion time and success in first attempt were recorded. Peak, plato and mean airway pressures, EtCO2, airway compliance and leak volume were periodically recorded during the operation. The presence of blood on device removal and postoperative sore throat were also assessed. RESULTS: The device insertion time in Group I-gel was shorter than that in Group LMA (21.00+/-4.15 vs. 30.40+/-12.17 s, p=0.001). The success rate in first attempt, peak, plato and mean airway pressures, EtCO2 and airway compliance did not differ between the groups. The leak volume was lower in Group I-gel 5 and 45 min after insertion (p=0.041 and p=0.027). The presence of blood on device removal and postoperative sore throat were similar in both groups. CONCLUSION: I gel may be a more advantageous supraglottic airway device compared with LMA. PMID- 27366519 TI - Comparison of Four Different Supraglottic Airway Devices in Terms of Efficacy, Intra-ocular Pressure and Haemodynamic Parameters in Children Undergoing Ophthalmic Surgery. AB - OBJECTIVE: The aim of this study was to compare insertion parameters of four different types of supraglottic airway devices (SGAD) (Classic LMA, I-gel LMA, Proseal LMA, Cobra PLA) in children undergoing ophthalmic surgery and to determine the effect on intra-ocular pressure (IOP) and haemodynamic responses during insertion. METHODS: Sixty American society of Anesthesiologists (ASA) I-II children aged 1-10 years undergoing extra-ocular ophthalmic surgery were randomly divided into four groups (Group LMA, Group I-gel LMA, Group PLMA and Group CPLA) in this prospective, randomised study. Anaesthesia was induced with decreasing sevoflurane concentrations (8%-2%) in a mixture of 50% N2O-O2. All SGADs were inserted under deep anaesthesia. The characteristics of insertion (number of attempts, ease and time), oropharyngeal leak pressure (OLP) and complications were recorded. IOP in both eyes, heart rate (HR), mean arterial pressure (MAP) and EtCO2 were measured before and 2 and 5 min after insertion of the SGADs. RESULTS: There was no difference between the groups in terms of the characteristics of insertion. The mean IOP did not increase significantly in all groups. MAP and HR changes were similar among the groups during follow-up. In all groups, HR increased 2 min after insertion (statistically insignificant) and returned to the baseline value 5 min after insertion. A statistically significant correlation was seen between HR increase and IOP values before and after insertion of the SGADs (p=0.006, correlation coefficient=0.352). Desaturation was seen in one patient in Groups LMA, PLMA and CPLA, and laryngospasm was seen in two patients in Group CPLA and in one patient in Group LMA. CONCLUSION: It was seen that during insertion of Classic LMA, I-gel LMA, Proseal LMA and Cobra PLA, IOP did not increase and haemodynamic stability was maintained in children undergoing extra-ocular ophthalmic surgery. PMID- 27366520 TI - Effect of Ketamine, Thiopental and Ketamine-Thiopental Combination during Electroconvulsive Therapy for Depression. AB - OBJECTIVE: We aimed to evaluate the effect of anaesthesia with thiopental (4 mg kg(-1)), ketamine (1 mg kg(-1)) and ketamine-thiopental (1 mg kg(-1) and 4 mg kg( 1), respectively) combination during electroconvulsive therapy (ECT) on the Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HAM-A) and haemodynamic variables in patients with resistant major depression. METHODS: Patients with HDRS scores above 17 were included. The patients were randomly divided into three groups according to the anaesthesia used. Group 1 was given thiopental (4 mg kg(-1)), Group 2 was given ketamine (1 mg kg(-1)) and Group 3 was given ketamine (1 mg kg(-1)) and thiopental (4 mg kg(-1)). Succinylcholine (1 mg kg(-1)) was administered in all patients for muscle relaxation. HDRS and HAM-A scores were evaluated before ECT, after 3, 6. ECT and after the final ECT. Systolic and diastolic blood pressures, heart rates and oxygen saturations were recorded before and after anaesthesia induction and after the ECT procedure. Seizure duration was recorded. RESULTS: Fifty-eight patients were included in the study. Thirty (52%) patients were male and 28 (48%) were female. The mean age was 42.7+/-15.8 years in Group 1, 44.8+/-11 years in Group 2 and 38.6+/-6.8 years in Group 3. In all groups, HDRS scores were reduced compared with the baseline values. There was no statistical significant difference between the groups regarding HDRS scores. HAM-A scores were higher in Group 2 and Group 3. Systolic and diastolic blood pressures and heart rate values were lower in Group 1 and the difference was statistically significant. CONCLUSION: In this study, anaesthesia induced with thiopental, ketamine and thiopental-ketamine combination was observed to not result in a difference in ECT for patients with treatment resistant depression. Ketamine at a dose of 1 mg kg(-1) given just before ECT did not enhance the antidepressant effect of ECT; however, anxiety scores were increased with ketamine application. PMID- 27366521 TI - Ultrasound-Guided Rectus Sheath Block in Gynaecological Surgery with Pfannenstiel Incision. AB - OBJECTIVE: This study aimed to evaluate the effects of ultrasound-guided rectus sheath block in gynaecological surgery with Pfannenstiel incision. METHODS: After the approval of the ethics committee and the patients' consent, 75 ASA I-II patients who were aged between 20 and 70 years and scheduled for a gynaecological surgery with Pfannenstiel incision were included in this study. After induction of general anaesthesia, patients were randomly divided into three groups. In Group UR patients (n=25), ultrasound-guided rectus sheath block with 0.25% levobupivacaine (0.2 mL kg(-1)) was performed. In Group SR patients (n=25), surgical rectus sheath block with 0.25% levobupivacaine (0.2 mL kg(-1)) was applied. In Group T (n=25) patients, tramadol (2 mg kg(-1)) was intravenously administered 30 min before the end of surgery. Patient-controlled analgesia device was established for postoperative pain relief in all groups. Haemodynamic data and inspired sevoflurane concentration were recorded during the operation. Pain scores, total tramadol consumption, supplemental analgesic requirement and side effects were postoperatively evaluated. RESULTS: Demographic characteristics, duration of surgery and haemodynamic parameters were similar between the groups. Inspired sevoflurane concentration (%) and VAS scores were significantly lower in Group UR than those in Groups SR and T. Total tramadol consumption was significantly lower in Groups UR and SR than that in Group T. There was no significant difference in the incidence of side effects. CONCLUSION: This study demonstrates that ultrasound-guided rectus sheath block helps to provide the effective analgesia without any side effects compared with surgical rectus sheath block and intravenous tramadol for gynaecological surgery with Pfannenstiel incision. PMID- 27366522 TI - Use of Succinylcholine by Anaesthetists in Turkey: A National Survey. AB - OBJECTIVE: Although succinylcholine (SCh) has side effects, it is among the most commonly used muscle relaxants for rapid induction because of the faster onset of its effects and short effect duration. However, there is no information regarding the frequency of use of SCh by anaesthetists in Turkey. This study aims to investigate the use of SCh by anaesthetists working in Turkey. METHODS: A web based survey form was sent by e-mail to anaesthetists working in Turkey. The form comprised a total of 24 questions. RESULTS: E-mails were sent to a total of 1882 addresses at two separate times. E-mail replies were received from 433 (23%) anaesthetists. Based on those who responded to the survey, 54.27% anaesthetists routinely used SCh for adult elective cases, 29.33% for paediatric elective cases and 74.13% for emergency cases. In adult elective cases, SCh was most frequently chosen for caesarean section (20.5%), and in paediatric elective and emergency cases, SCh was chosen most frequently because difficult intubation was expected (31.3 and 21.4%, respectively). CONCLUSION: Our study reveals that SCh is still widely used by anaesthetists in Turkey. Majority of physicians who participated our survey were aware of the side effects; however, they reported using SCh in certain special situations. It is evident that creation of a standard care guide for departments is essential. The first stage of creating a standard care guide is to analyse and document the current application. With this aim, more wide ranging advanced studies should be completed. PMID- 27366523 TI - Retrospective Evaluation of Dental Treatment under General Anaesthesia. AB - OBJECTIVE: Most dental procedures can be performed with local anaesthesia, however noncompliant paediatric patients, patients with mental retardation or psychiatric disorders, severe anxiety, severe craniofacial anomalies and orofacial trauma may need general anaesthesia. In these patients accompanying central nervous system diseases and airway problems increase the risk of complications. Anaesthesia records of 467 cases of dental surgery performed under general anaesthesia between 2011-2014 is reported with information from the recent literature. METHODS: In the study, 467 cases of dental procedures performed under general anaesthesia were taken from the Inonu University of Medicine, Dentistry Disabled Treatment Centre, after approval of the Inonu University Faculty of Medicine Ethics Committee. Demographic data, ASA classification, Mallampati (MP) score, duration of surgery, type of intubation and difficulties, comorbid diseases, premedication application, endocarditis prophylaxis, recovery time, analgesia and reasons for general anaesthesia were recorded as mean+/-standard deviation (SD) or as a number. RESULTS: The mean age of the patients was 16.78+/-12 years and the female/male ratio was 277/190 (59.3%/40.7%). Of the 467 patients, 219 (46.9%) were classified as ASA I, 234 (50.1%) as ASA II and 14 (3%) as ASA III. Furthermore, 182 (38.9%) patients with mental retardation, 33 (7.1%) with cerebral palsy and 28 (6%) with autism were identified. The mean operative time was 114.53+/-35.4 min, and the average recovery time 40.4+/-6 was min. Of the endotracheal intubations 277 (59.3%) were oral, 82 (17.6%) were nasal, and 108 (23.1%) were nasal with the help of fibreoptics. Difficult intubation was observed in 20 (4.3%) patients. The MP score was 1 in 397 (85%) patients, 2 in 50 (10.7%) patients, 3 in 18 (3.9%) patients and 4 in 2 (0.4%) patients. General anaesthesia was applied because of cooperation difficulties in 213 (45.6%), mental retardation in 182 (38.9%), autism in 28 (5.9%), schizophrenia in 7 (1.7%) and jaw surgery in 37 (7.9%) patients. Local infiltration was used for analgesia in 141 (30.2%), morphine in 12 (2.6%), tramadol in 3 (0.6%) and paracetamol in 311 (66.6%) patients. Endocarditis prophylaxis was employed in 36 (7.7%) cases. CONCLUSION: General anaesthesia in dental procedures is becoming increasingly common. Anaesthetic management is important due to the frequency of genetic syndromes and mental retardation. In the anaesthetic management of these patients, strategies for the patient should be identified, the process should be implemented in the operating room and preparations should be made with risk analyses. PMID- 27366524 TI - Neuromuscular Functions on Experimental Acute Methanol Intoxication. AB - OBJECTIVE: The incidence of accidental or suicidal ingestion of methyl alcohol is high and methyl alcohol intoxication has high mortality. Methyl alcohol intoxication causes severe neurological sequelae and appears to be a significant problem. Methyl alcohol causes acute metabolic acidosis, optic neuropathy leading to permanent blindness, respiratory failure, circulatory failure and death. It is metabolised in the liver, and its metabolite formic acid has direct toxic effects, causing oxidative stress, mitochondrial damage and increased lipid peroxidation associated with the mechanism of neurotoxicity. Methanol is known to cause acute toxicity of the central nervous system; however, the effects on peripheral neuromuscular transmission are unknown. In our study, we aimed to investigate the electrophysiological effects of experimentally induced acute methanol intoxication on neuromuscular transmission in the early period (first 24 h). METHODS: After approval by the Animal Experiment Ethics Committee of Ege University, the study was carried out on 10 Wistar rats, each weighing about 200 g. During electrophysiological recordings and orogastric tube insertion, the rats were anaesthetised using intra-peritoneal (IP) injection of ketamine 100 mg kg( 1) and IP injection of xylazine 10 mg kg(-1). The rats were given 3 g kg(-1) methyl alcohol by the orogastric tube. Electrophysiological measurements from the gastrocnemius muscle were compared with baseline. RESULTS: Latency measurements before and 24 h after methanol injection were 0.81+/-0.11 ms and 0.76+/-0.12 ms, respectively. CMAP amplitude measurements before and 24 h after methanol injection were 9.85+/-0.98 mV and 9.99+/-0.40 mV, respectively. CMAP duration measurements before and 24 h after methanol injection were 9.86+/-0.03 ms and 9.86+/-0.045 ms, respectively. CONCLUSION: It was concluded that experimental methanol intoxication in the acute phase (first 24 h) did not affect neuromuscular function. PMID- 27366525 TI - Preoperative Psychological Preparation of Children. AB - Surgery and anaesthesia are significant sources of anxiety for children. In the preoperative period, reducing anxiety helps in preventing the negative consequences that may occur after surgery. The predetermined high-risk children in terms of the development of anxiety play an important role in reducing the negative consequences. Recently featured approaches are modelling and coping techniques, although many techniques are used in the preoperative psychological preparation. The use of computer programs in this area may facilitate important achievements, and it needs to support new studies to be performed. PMID- 27366526 TI - Synthetic Cannabinoid 'Bonzai' Intoxication: Six Case Series. AB - In the language of the streets, 'bonzai', known as '1-naphthalenyl of methanol', also known as JWH-18 group, is a drug belonging to the group of synthetic cannabinoids. At the beginning of 2004, it started to be sold on the internet and it is seen that private markets. It has structurally similar chemical characteristics as delta 9-tetrahydrocannabinol (THC), the active substance in marijuana. In 2013, in a study conducted by the European Monitoring Centre of Drugs and Drug Addiction (EMCDDA), 102 varieties of synthetic cannabinoids were identified; however, more than 200 substances have been reported since 1997. In this study, we report the difficulties in the clinical course, treatment and management of six patients that had a use history of bonzai although it was not detected in blood in a short period of time in the intensive care unit. PMID- 27366527 TI - Difficult Airway Management in Field Conditions: Somalia Experience. AB - Difficult airway is defined as having the patient's mask ventilation or difficult tracheal intubation of an experienced anaesthesiologist. A number of reasons, such as congenital or acquired anatomical anomalies, can cause difficult intubation and difficult ventilation. Keeping all equipment ready for airway management of patients will reduce mortality and complications. In this case, it is intended that the submission of difficult airway management who encountered in mandibular reconstruction for mandible bone defect repairing with reconstruction plates before at the field conditions in Somalia. PMID- 27366528 TI - Anaesthesia Management and Use of Sugammadex in a Patient with Ullrich's Disease. AB - Here, we report anaesthesia management and the successful use of total intravenous anaesthesia and sugammadex in a patient with Ullrich's disease. Propofol and remifentanyl infusion was used for anaesthesia. After the end of the surgery, when the train-of-four value was 0%, 4 mg kg(-1) sugammadex was administered, and the patient was successfully extubated after 36 s. No adverse effects or safety concerns were observed. In conclusion, we suggest that the use of propofol infusion to avoid the use of inhalation anaesthetics and the use of sugammadex for the reversal of the effects of rocuronium is safe in patients with Ullrich's disease. PMID- 27366529 TI - Anaesthesia Management in a Patient with Waardenburg Syndrome and Review of the Literature. AB - Waardenburg syndrome is a rare autosomal dominant disease that may cause hearing loss, pigmentary abnormalities, neurocristopathy and partial albinism. Incidence is estimated as 2%-3% among the cases of congenital deafness and 1/42,000 of the general population. Children with Waardenburg syndrome usually require anaesthesia for the cochlear implant operation in early age. The features of the syndrome that may bear importance for anaesthetic management are laryngomalacia, multiple muscle contractures, limited neck movements, cyanotic cardiopathy and electrolyte imbalance. Patients with Waardenburg syndrome stand for difficult airway. We aimed to report anaesthetic management of a child with Waardenburg syndrome who underwent surgery for cochlear implantation. PMID- 27366530 TI - Airway Surgery in Tracheostomised Patients with Wegener Granulomatosis Leading to Subglottic Stenosis. AB - Wegener granulomatosis (WG) is a multisystemic disorder characterised by granulomatous inflammation of the respiratory system. The growing of proliferative tissue towards the larynx and trachea may cause airway obstruction on account of subglottic stenosis. In this situation, the surgical goal is to eliminate the airway obstruction by providing natural airway anatomy. While mild lesions do not require surgical intervention, in fixed lesions, surgical intervention is required, such as tracheostomy, laser resection and dilatation. In tracheostomised patients, granuloma formation surrounding the tracheostomy cannula may occur in the trachea. Inflammation and newly formed granulation tissue result in severe stenosis in the airways. During surgical treatment of such patients, airway management is important. In this case report, we will discuss gas exchange and airway management with jet ventilation (JV) during excision of the granulation tissue with endolaryngeal laser surgery, leading to subglottic stenosis in tracheostomised patients in WG. PMID- 27366531 TI - Simultaneous Bilateral Carotid Endarterectomy under Cervical Plexus Blockade. AB - In patients with severe carotid artery stenosis who developed transient ischemic attack, carotid endarterectomy is one of the most effective treatments. In particular, in patients with contralateral carotid artery lesions, there is a risk of serious neurologic complications during the intra-operative period. Experienced staff can perform simultaneous bilateral carotid endarterectomy safely in carefully selected patients. The advantages of regional anaesthesia in carotid endarterectomy are evaluation of intra-operative neurological condition and defining correct indications for shunt usage. It is a cheap, reliable and easy method that reduces the length of stay in the intensive care unit and in the hospital and may influence the overall cost of care. However, it is important to make dose adjustments to avoid potential complications of nerve involvement during bilateral procedure. In this case report, we share our experiences regarding bilateral carotid endarterectomy under cervical plexus blockade. PMID- 27366532 TI - Post-Spinal a Rare Complication and Treatment: Tinnitus and Epidural Blood Patch. PMID- 27366533 TI - Retrospective Evaluation of Anaesthetic Techniques for Caesarean. AB - OBJECTIVE: This study aimed to evaluate the maternal, foetal and neonatal effects of anaesthetic techniques used in caesarean sections (C/S) retrospectively over 6 years at the Hospital of Medical School of Dokuz Eylul University and to compare the results with the literature from Turkey and developed countries. METHODS: After obtaining approval from the ethics committee, anaesthetic and gestational data from all caesarean operations performed over a 6-year period between 2005 and 2010 was retrospectively obtained from hospital archives. RESULTS: During this period, a total of 10,819 labours was conducted and C/S ratio was 55% with 5953 patients. General anaesthesia was performed in 1479 patients (24.8%) and regional anaesthesia was performed in 4474 patients (75.2%) [Spinal anaesthesia for 1203 patients (26.9%), epidural anaesthesia for 830 patients (18.5%) and combined spinal-epidural anaesthesia for 2441 patients (54.6%)]. In 2010, regional anaesthesia ratio increased to 84.6%, whereas in 2005, it was 63.8%. Regional anaesthesia was used significantly more often in both elective and urgent patients (82% elective and 65.2% emergency). Because of failed regional anaesthesia or surgical complications, anaesthesia was changed to general anaesthesia in 215 patients (4.8%). APGAR scores in 1 and 5 min were significantly higher with regional anaesthesia when compared with general anaesthesia. CONCLUSION: Regional anaesthesia rate for C/S patients in the Hospital of Medical School of Dokuz Eylul University is increased and is higher than Turkey's average; but these figures are still lower than those in the developed countries. PMID- 27366534 TI - Pseudocholinesterase Enzyme Deficiency in Adiyaman City Area. AB - OBJECTIVE: Pseudocholinesterase (PChE) is an enzyme responsible for the hydrolysis of succinylcholine. In case of its deficiency, the effect of succinylcholine that is approximately 5-10 min is prolonged up to few hours. The use of succinylcholine has been declined recently. However, it is still actively used in some special conditions and in developing countries. In this study, incidence of PChE enzyme deficiency around Adiyaman city was investigated and presented with the literature review. METHODS: After obtaining an approval from the investigational board of our hospital (Adiyaman University Medical School, Biomedical Research Ethics Board, 30.12.2012, Nr: B.30.2.ADY.0.20.00-600/51), patients undergoing any elective operation under general anaesthesia in the Adiyaman University Medical School Hospital between March and December 2013 were recruited for the study. After obtaining the patients' written consents, blood PChE, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine, international normalisation ratio (INR) and activated partial thromboplastin time (aPTT) values of the patients were analysed. Possible association of the PChE deficiency with other values was also investigated. The normal value of PChE was taken as 4260-11250 for females aged 16-40 years and 5320-12920 U L(-1) for other patients. RESULTS: The study was completed with 964 patients, 702 (72.8%) of whom were females. PChE enzyme levels were under the normal in 7.2% of the patients. There were no correlation between patient group, ALT, INR, aPTT and creatinine elevation with PChE deficiency (p>0.05), whereas AST and urea level elevation was significantly associated with PChE deficiency (p<0.05). The risk of PChE deficiency was 4.5 and 9 times higher in the patients with the elevation of AST and urea levels, respectively. CONCLUSION: Pathological elevations of AST and urea that are a part of normal pre-operative biochemical analysis of blood will indicate the possible deficiency of PChE enzyme. PMID- 27366535 TI - Comparison of Sugammadex versus Neostigmine Costs and Respiratory Complications in Patients with Obstructive Sleep Apnoea. AB - OBJECTIVE: To compare sugammadex and neostigmine regarding the efficacy in reversing rocuronium-induced neuromuscular block, the incidence of post-operative respiratory complications and costs in patients undergoing surgery for the treatment of obstructive sleep apnoea (OSA). METHODS: After obtaining ethical approval and patient consent, 74 patients in ASA physical status I or II were randomised into two groups to receive 2-mg kg(-1) sugammadex (Group S) or 0.04-mg kg(-1) neostigmine+0.5-mg atropine (Group N). Groups were compared regarding time to TOF (train-of-four) 0.9, operating room time, post-anaesthesia care unit (PACU) stay, post-operative respiratory complications, costs related to neuromuscular block reversal, anaesthesia care and complication treatment. RESULTS: Patient demographics, anaesthesia, surgical data and total rocuronium doses were similar between groups. Time to TOF 0.9 was shorter for group S [Group N: 8 (5-18) min; Group S: 2 (1.5-6) min (p<0.001)]. Operating room time [Group S: 72.4+/-14.3 min; Group N: 96.6+/-22.8 min (p<0.001)] and PACU stay [Group S: 22.9+/-10.1 dk; Group N: 36.3+/-12.6 dk (p<0.001)] were also shorter in Group S. After extubation, desaturation was observed in 12 (32.4%) patients in group N and in 4 (8%) patients in group S (p=0.048). In group N, three patients were reintubated; there were eight (21.6%) unplanned intensive care unit (ICU) admissions. There was one unplanned ICU admission in group S. Negative pressure pulmonary oedema was observed in one patient in group N. The results regarding costs were as follows. The reversal cost was higher in the sugammadex group (vial cost 98.14 TL) than that in the neostigmine group (ampoule cost 0.27 TL; total 6147.88 TL vs. 3569.5 TL); however, complication treatment cost and total cost were lower in group S than those in group N (199.5 TL vs. 3944.6 TL) (staff anaesthesia doctor cost was 0.392 TL per min and the cost of nurse anaesthetist was 0.244 TL per min). CONCLUSION: This study confirmed the efficacy of sugammadex over neostigmine for the reversal of rocuronium-induced neuromuscular block. Sugammadex decreases the incidence of post-operative respiratory complications and related costs in patients with OSA. PMID- 27366536 TI - Evaluation of Public Awareness, Knowledge and Attitudes about Cardiopulmonary Resuscitation: Report of Izmir. AB - OBJECTIVE: Early initiation of cardiopulmonary resuscitation (CPR) by witnesses increases survival after cardiac arrest. In Turkey, our country, it is rare that basic life support (BLS) is initiated by a layperson. In our study, we aimed to use a survey to research awareness, level of knowledge and attitudes of the public to CPR and BLS. METHODS: A 21-question survey was administered to individuals aged >=18 years on a busy street in a city of a western region of Turkey. Topics such as knowledge about cardiac arrest findings, previous experience of CPR, knowledge of BLS and concerns related to CPR were questioned. RESULTS: The fully completed forms of 533 people were evaluated. There were 40.7% who stated that they had received training in CPR. For signs of cardiac arrest, 40.7% answered loss of consciousness, 49.3% answered cessation of breathing and 60.7% answered cessation of circulation. It was found that 35.5% could perform only chest compressions, 27.6% could perform mouth-to-mouth ventilation and 28.7% able to perform both. While 52.0% knew the location for performing chest compressions, 34.3% knew the correct depth and 15.6% knew the correct compression ventilation rate. Bystander CPR was performed by 3.6%. CONCLUSION: In conclusion, 40.7% of people living in a highly educated region in the western part of Turkey had received CPR training and 3.6% performed bystander CPR. A majority of participants stated that they were willing to correct and develop their knowledge and skills related to CPR. Effective public CPR training programmes may increase the knowledge and awareness of CPR in the adult population. PMID- 27366537 TI - Comparison of the Supraglottic Airway Devices Classic, Fastrach and Supreme Laryngeal Mask Airway: A Prospective Randomised Clinical Trial of Efficacy, Safety and Complications. AB - OBJECTIVE: This prospective randomised study was designed to compare the Laryngeal Mask Airway (LMA) Classic, LMA Fastrach and LMA Supreme regarding ease of insertion and insertion time as primary outcomes and reposition, success rate of trials, effects on haemodynamic parameters, provision of an adequate and safe airway, amount of leakage and oropharyngeal and systemic complications as secondary outcomes. METHODS: In this clinical trial, 90 patients aged 18-70 years of American Society of Anesthesiologists (ASA) group I-II were randomised into three groups as providing airway via LMA Classic, LMA Fastrach or LMA Supreme instead of tracheal intubation. No muscle relaxant was used. The allocated LMA was inserted by the same anaesthetist; bispectral index (BIS) was between 40% and 60%. RESULTS: There was no statistical difference among the groups regarding the ease of insertion and insertion time as primary outcomes; the incidence of repositioning during placement was significantly higher in the LMA Classic group than that in other groups (p<0.05) and the rates of bloodstain on the device as well as oropharyngeal mucosal oedema were higher in the LMA Fastrach group than those in other groups (p<0.05) as secondary outcomes. CONCLUSION: We suggest that LMA Classic, LMA Supreme and LMA Fastrach had similar effectiveness regarding efficiency and airway safety. However, LMA Supreme seems to be more advantageous as it is more appropriate for fewer oropharyngeal complications and there was no repositioning. PMID- 27366538 TI - Intracranial Pressure Monitoring as a Part of Multimodal Monitoring Management of Patients with Critical Polytrauma: Correlation between Optimised Intensive Therapy According to Intracranial Pressure Parameters and Clinical Picture. AB - OBJECTIVE: Trauma patient requires a complex therapeutic management because of multiple severe injuries or secondary complications. The most significant injury found in patients with trauma is head injury, which has the greatest impact on mortality. Intracranial pressure (ICP) monitoring is required in severe traumatic head injury because it optimises treatment based on ICP values and cerebral perfusion pressure (CPP). METHODS: From a total of 64 patients admitted in the intensive care unit (ICU) 'Casa Austria', from the Polytraumatology Clinic of the Emergency County Hospital "Pius Brinzeu" Timisoara, Romania, between January 2014 and December 2014; only patients who underwent ICP monitoring (n=10) were analysed. The study population was divided into several categories depending on the time passed since trauma to the time of installation of ICP monitoring (<18 h, 19-24 h and >24 h). Comparisons were made in terms of the number of days admitted in the ICU and mortality between patients with head injury who benefited and those who did not benefit from ICP monitoring. RESULTS: The results show the positive influence of ICP monitoring on the number of admission days in ICU because of the possibility that the number of admission days to augment therapeutic effects in patients who benefited from ICP monitoring reduces by 1.93 days compared with those who did not undergo ICP monitoring. CONCLUSION: ICP monitoring and optimizing therapy according to the ICP and CPP has significant influence on the rate of survival. ICP monitoring is necessary in all patients with head trauma injury according to recent guidelines. The main therapeutic goal in the management of the trauma patient with head injury is to minimize the destructive effects of the associated side effects. PMID- 27366539 TI - Primary Graft Dysfunction after Lung Transplantation. AB - Primary graft dysfunction (PGD) is a severe form of acute lung injury that is a major cause of early morbidity and mortality encountered after lung transplantation. PGD is diagnosed by pulmonary oedema with diffuse alveolar damage that manifests clinically as progressive hypoxemia with radiographic pulmonary infiltrates. Inflammatory and immunological response caused by ischaemia and reperfusion is important with regard to pathophysiology. PGD affects short- and long-term outcomes, the donor organ is the leading factor affecting these adverse ramifications. To minimize the risk of PGD, reduction of lung ischaemia time, reperfusion optimisation, prostaglandin level regulation, haemodynamic control, hormone replacement therapy, ventilator management are carried out; for research regarding donor lung preparation strategies, certain procedures are recommended. In this review, recent updates in epidemiology, pathophysiology, molecular and genetic biomarkers and technical developments affecting PGD are described. PMID- 27366540 TI - Colostomy with Transversus Abdominis Plane Block. AB - Transversus abdominis plane (TAP) block is one of the abdominal field block. The TAP block is used for both anaesthetic management and post-operative pain therapy in lower abdominal surgery. TAP block is a procedure in which local anaesthetic agents are applied to the anatomic neurofacial space between the internal oblique and the transversus abdominis muscle. TAP block is a good method for post operative pain control as well as allows for short operations involving the abdominal area. In this article, a case of colostomy under TAP block is presented. PMID- 27366541 TI - Anaesthetic Management in Costello Syndrome. AB - Costello syndrome is a rare genetic disorder characterised by growth and mental retardation, macrocephaly, short neck and macroglossia. Cardiac involvement can also occur in Costello syndrome and is presented in the form of hypertrophic cardiomyopathy, tachyarrythmias and valvular dysfunction. Nervous system involvement including ventriculomegaly, hydrocephaly and Chiari type 1 malformation are also common. Predisposition of papillomata and malignant tumours are high. General anaesthesia practice in patients with Costello syndrome may be complicated by difficult airway because of macrocephaly, short neck, macroglossia and oral or laryngeal papillomas. The airway management and cardiac abnormalities are the major concerns of an anaesthesiologist in Costello syndrome. We report the anaesthetic management of ventriculo-peritoneal shunt replacement for hydrocephaly in an 18-month-old child with Costello syndrome. PMID- 27366542 TI - Post-Operative Malignant Hyperthermia in a Child after Colon Interposition. AB - Malignant hyperthermia (MH) is a rare and potentially life threatening fatal complication of anaesthesia. We present a 2-year-old boy with late onset MH after colon interposition to replace the oesophagus under sevoflurane anaesthesia. The patient was treated with intravenous dantrolene sodium as well as cooling and controlled ventilation. Despite treatment, the patient developed cardiopulmonary arrest at 21 hours after the operation and died. It should be kept in mind that post-operative MH may develop during these types of operations with ischaemia reperfusion injuries. PMID- 27366543 TI - A Case Report of the First Propofol Addiction in Turkey. AB - Propofol is a potent anaesthetic drug and also an effective sedative agent. Also, propofol may be used for non-anaesthetic purposes such as the treatment of seizures, migraine and tension headache in clinical practice. It has been abused, particularly among healthcare providers with high mortality rate. This report presents the case of a propofol-dependent patient who was an emergency medicine doctor with no difficulties in obtaining the drug. He himself visited our clinic for the treatment of propofol dependence. We started the patient's treatment with pharmacotherapeutic medicines and individual psychotherapy. Fourteen days after starting the therapy, the patient was discharged from hospital on his own will and he did not attend the follow-up visits in the outpatient clinic. Then, we were informed of his death, which was suspected to have occurred owing to drug intoxication in the hospital in which he worked. Nevertheless, the reason of death was important; the importance of this case report is to provide information regarding the drug's dependence profile. This is the first case report indicating propofol dependence in Turkey. Because of its easy access, rapid onset time and short duration of action, propofol dependence is increasing. We think that adding propofol to the controlled drug list and improving the knowledge of the clinicians regarding its abuse potential may limit the dependence cases. PMID- 27366544 TI - Ultrasound-Guided Bilateral Greater Occipital Nerve Block for Mass Excision. AB - Anaesthesiologists must always prefer the safest method to minimize the risk for patients. At present, ultrasound-guided blockage of the greater occipital nerve can be performed in a safe manner. In this report, we presented our experience of ultrasound-guided blockage of the greater occipital nerve that we performed in a patient with a mass at the back of the neck who had risk of general anaesthesia because of comorbidities. PMID- 27366545 TI - Can the Endotracheal Tube Become a Threat to Airway Patency? PMID- 27366546 TI - Chemotherapy Related Angioedema. PMID- 27366547 TI - Release Pattern of Liposomal Bupivacaine in Artificial Cerebrospinal Fluid. AB - OBJECTIVE: We aimed to compare the possible controlled release profile of multilamellar liposomal bupivacaine formulations with non-liposomal forms in artificial cerebrospinal fluid (CSF) under in vitro conditions. METHODS: Liposome formulations were prepared using a dry-film hydration method. Then, an artificial CSF-buffered solution was prepared. Bupivacaine base with liposomal bupivacaine base, bupivacaine HCl with liposomal bupivacaine HCl and bupivacaine HCl were added in a Franz diffusion cell. These solutions were kept in a hot water bath for 24 h. The samples were taken at 0.5, 1, 3, 6, 12 and 24 h (1st series of experiment). Solutions of bupivacaine base with liposomal bupivacaine base and bupivacaine HCl with liposomal bupivacaine HCl were centrifuged to obtain liposomal bupivacaine base and liposomal bupivacaine HCl. Afterwards, liposomal bupivacaine base and liposomal bupivacaine HCl were added in a Franz diffusion cell. After keeping these solutions in a hot water bath for 24 h as well, the samples were taken at the same time intervals (2(nd) series of experiment). All samples (54 from the 1st experiment and 36 from the 2(nd) experiment) were analysed with high-performance liquid chromatography and ultra-performance liquid chromatography and their chromatograms were obtained. RESULTS: After obtaining calibration curves for bupivacaine base and HCl, release patterns of these formulations were plotted. A markedly controlled slow-release pattern was observed for multilamellar liposomal bupivacaine than for non-liposomal bupivacaine in artificial CSF. CONCLUSION: Demonstration of controlled slow release profile for mutilamellar liposomal bupivacaine in artificial CSF in vitro might support intrathecal use of liposomal bupivacaine in vivo in animal studies. PMID- 27366548 TI - Acupuncture as an Antiemetic in Children who Underwent Adenoidectomy and/or Tonsillectomy. AB - OBJECTIVE: Postoperative vomiting (POV) is one of the most common problems following general anaesthesia, and many factors, either solely or in combination, may play a role in aetiology. Acupuncture is a technique that the World Health Organization has accepted as a complementary treatment. This study presents our experience with acupuncture for POV treatment in a study of paediatric tonsillectomy cases. METHODS: The study included ASA I-II patients (n=70) aged 2 14 years who underwent tonsillectomy and/or adenoidectomy under general anaesthesia. The patients were randomly divided into the following two groups: control and study group. In the study group, an acupuncture needle was intraoperatively applied to the P6 acupuncture point for 20 min. Antiemetics were not administered to either group because of the standard applications in the preoperative period. The patients were postoperatively evaluated by nurses who were unaware about the techniques used in either group. RESULTS: No statistically significant difference was determined between the groups with regard to age, sex, nature of the operation, duration of anaesthesia, duration of the operation, surgical method and ASA scores. A statistically significant difference was determined between the groups with respect to vomiting rates. The acupuncture group presented with 0.28-times fewer vomiting episodes than the control group. CONCLUSION: The results of the study demonstrate that acupuncture has an apparent antiemetic efficacy in POV. Its routine use for POV may improve postoperative comfort and reduce drug use for prophylactic or therapeutic purposes. PMID- 27366549 TI - Comparison of Clinical Effects of Dexketoprofen and Paracetamol Used for Analgesia in Endoscopic Retrograde Cholangiopancreatography. AB - OBJECTIVE: This study aimed to compare 50 mg dexketoprofen vs. 1 g paracetamol that were parenterally administered before endoscopic retrograde cholangiopancreatography (ERCP) under sedoanalgesia with comparable anaesthesia depth regarding haemodynamic, pain, narcotic analgesic requirement, recovery and post-procedural cognitive functions. METHODS: Overall, 80 ASA I-III patients aged 18-75 years who were undergoing scheduled ERCP were randomly assigned into three groups. In all patients, the mini-mental test (MMT) was conducted before the procedure. No drug was administered to controls (Group C; n=26); patients were transferred to ERCP unite 30 min after parenteral dexketoprofen (50 mg) in group D (n=27) and paracetamol (1 g) in group P (n=27). The standard monitoring was applied. After intravenously administering loading doses of midazolam (0.02 mgkg) and propofol (1 mg kg(-1)), propofol infusion was administered at a dose of 2-4 mg kg(-1) h(-1) to maintain a bispectral index value of 50-70. Fentanyl (0.05 MUg kg(-1)) was intravenously administered when patients experienced pain. Haemodynamic effects, additional analgesic requirement, adverse effects during procedure, time to reach Aldrete score of 9 and satisfaction of an endoscopist and patient were recorded. MMT was repeated 3 h after completing the procedure. RESULTS: Fentanyl requirement during the procedure was significantly low in group D (p<0.05). Apnoea during the procedure and nausea after the procedure were least common in group D while significantly lower than group C (p<0.05). There was no significant difference with respect to MMT scores and endoscopist's satisfaction, while patient satisfaction was greater in group P. CONCLUSION: Parenterally administered dexketoprofen provided better haemodynamic effect and pain control, thereby decreasing incidence of adverse events by reducing the requirement for narcotic analgesics. PMID- 27366550 TI - Perioperative Effects of Different Narcotic Analgesics Used to Improve Effectiveness of Total Intravenous Anaesthesia. AB - OBJECTIVE: We aimed to evaluate the depth of anaesthesia, perioperative haemodynamics, postoperative pain scores, analgesic consumption in patients receiving remifentanil- or alfentanil-based total intravenous anaesthesia for single-level lumbar discectomy. METHODS: Seventy patients undergoing discectomy were enrolled in the study. Patients were intravenously administered an initial bolus dose of 2 mg kg(-1) propofol and 10 mcg kg(-1) alfentanil or 1 mcg kg(-1) remifentanil, followed by 6 mg kg(-1) h(-1) propofol and either 1 mcg kg(-1) min( 1) alfentanil or 0.25 mcg kg(-1) min(-1) remifentanil infusion. Bispectral index (BIS) values, mean arterial pressure, heart rate, end-tidal carbon dioxide and oxygen saturation were recorded. Postoperative pain scores at 0, 30 and 60 min were measured and recorded with additional opioid requirements. RESULTS: Postoperative pain scores at 0 and 30 min, total analgesic consumption and requirement for additional analgesics were significantly high in the remifentanil group. After the first hour, the pain scores were not significantly different. Mean arterial blood pressure was significantly low at 45 and 60 min preoperatively in the remifentanil group. In the remifentanil group, heart rate at 15, 30, 45, 60 min were significantly lower than those in the alfentanil group. BIS values of the two groups were not significantly different at any measurement time point. BIS values of remifentanil group at 30, 45, 60, 90 and 180 min significantly increased compared with those at 15 min. CONCLUSION: Alfentanil provided more stable BIS and haemodynamic values preoperatively and less opioid consumption, along with lower pain scores, during the early postoperative period compared with remifentanil in patients undergoing single level discectomy. PMID- 27366551 TI - Influence of Different Doses of Ketamine on Intubating Conditions during a Rapid Sequence Induction and Intubation Model. AB - OBJECTIVE: This prospective, randomized, double-blinded study aimed to compare the effects of three different doses of ketamine or lidocaine on intubating conditions and haemodynamics in a rapid-sequence induction model with 3 mg kg(-1) propofol and 0.6 mg kg(-1) rocuronium. METHODS: A total of 128 ASA I-III patients who were scheduled for elective surgery were randomized in the following five groups: Group 1 (n=24), 1 mg kg(-1) lidocaine+3 mg kg(-1) propofol+0.6 mg kg(-1) rocuronium; Group 2 (n=23), 0.1 mg kg(-1) ketamine+3 mg kg(-1) propofol+0.6 mg kg(-1) rocuronium; Group 3 (n=29), 0.3 mg kg(-1) ketamine+3 mg kg(-1) propofol+0.6 mg kg(-1) rocuronium; Group 4 (n=26), 0.5 mg kg(-1) ketamine+3 mg kg(-1) propofol+0.6 mg kg(-1) rocuronium and Group 5 (n=26), 3 mg kg(-1) propofol+0.6 mg kg(-1) rocuronium+saline as placebo. After preoxygenation, induction was performed with the assigned combination, and intubation was initiated after 60 s. The time to intubation, intubation score (Viby-Mogensen score) and haemodynamic data were recorded. Postoperative hoarseness, sore throat and hallucination incidences were followed up. RESULTS: Demographic, time to intubation and haemodynamic data were comparable among groups. Group 4 [13.5 (4 14)] revealed a higher intubation score then groups 1, 2 and 5 [12 (3-14), 11 (2 14) and 9.5 (0-13) and p=0.026, p=0.001 and p=0.000001, respectively]. Groups 3 [13 (4-14)] and 4 [13.5 (4-14)] had similar intubation scores. Side effects were comparable among all groups. CONCLUSION: The combination of 0.5 mg kg(-1) ketamine and 0.6 mg kg(-1) rocuronium along with propofol improves intubation conditions in a stimulated rapid-sequence induction model. PMID- 27366552 TI - Comparison of Laryngeal Mask Airway Supreme(TM) Versus Unique(TM) in Edentulous Geriatric Patients. AB - OBJECTIVE: It is more difficult to perform bag-mask ventilation in edentulous patients than in patients with intact dentition. The laryngeal mask airway (LMA) provides a better alternative to the standard face mask if the facial contours of the patient are not suited for the standard face mask. We aimed to compare these two different LMAs in edentulous geriatric patients. METHODS: Edentulous patients aged >=65 years of American Society of Anesthesiologists physical status I-III were included in the study. They were randomly assigned to Supreme group (n=30) and Unique group (n=30). Success of first insertion attempt, ease and time of insertion and oropharyngeal leak pressure were recorded. RESULTS: The success rate of the first insertion attempt was higher in the Supreme group than in the Unique group (86.6 and 73.3%, respectively; p=0.04). Time of insertion was similar (10.04 s and 11.87 s, respectively) and insertion was easy in 90% and 100% of patients, respectively. Oropharyngeal leak pressures were measured as 20.56-cm H2O and 17.10-cm H2O for LMA SupremeTM and LMA UniqueTM, respectively. CONCLUSION: The efficacy and safety in both groups were comparable in edentulous geriatric patients during short surgical procedures. Even the success rate of insertion with both was lower than that mentioned in the literature; the success of insertion at the first attempt was superior with the LMA SupremeTM in our edentulous study group. PMID- 27366553 TI - Regional Anaesthesia Management in a Patient with Leprosy: Rare Case with Rare Application. AB - Leprosy is a chronic infectious disease that is caused by Mycobacterium leprae and affects the skin and nerves. Patients with leprosy having related peripheral neuropathy and involvement of other organs may have cardiac, respiratory dysautonomia and autonomic dysfunctions. There are very few studies regarding anaesthetic management of patients suffering from leprosy. Moreover, very few studies concerning regional anaesthesia in patients with lepromatous leprosy have been reported. In this study, we aim to assess regional anaesthesia management with combined spinal epidural anaesthesia in a patient who had been followed up with a diagnosis of leprosy for a long time and was scheduled for operation because of a femoral neck fracture. PMID- 27366554 TI - Management of Neuraxial Anaesthesia for Emergent Caesarean Section for Placenta Previa. AB - Abnormal placental attachments, such as placenta accreta, increta or percrata, can result in increased morbidity and mortality because of the risk of severe postpartum haemorrhage. We aimed to present the management of spinal anaesthesia and surgical approach for emergent caesarean section because of vaginal bleeding in a multiparous pregnant woman with placenta previa at 36 weeks' gestation. Hyperbaric bupivacaine 12 mg, fentanyl 10 MUg and morphine 150 MUg were intrathecally administered for spinal anaesthesia. Oxytocin, methyl ergonovin and tranexamic acid were administered after umbilical cord clamping. Breech delivery of the baby was provided by a vertical incision to the uterus for avoiding placental harm. Subtotal hysterectomy was performed leaving the placenta in situ. Two units of red blood cells were transfused during the operation, lasting approximately 40 min. The patient was uneventfully discharged on the postoperative fourth day. In conclusion, a single-shot spinal anaesthesia was successfully maintained without conversion to general anaesthesia until the end of the hysterectomy in the patient in whom placenta increta was observed during caesarean delivery. PMID- 27366555 TI - Anaesthetic Management of Laparoscopic Morgagni Hernia Repair in a Patient with Coexisting Down Syndrome, Patent Foramen Ovale and Pectus Carinatum. AB - Laparoscopic repair has several advantages with a minimally invasive surgical option for children with Morgagni hernias; however, a number of physiological sequelae results from pneumoperitoneum and insufflation. These physiological changes may be more significant in patients with a congenital heart disease. Perioperative detailed evaluation, meticulous monitorization and cooperation with a surgical team are important in cases with patent foramen ovale for the possible risk of the paradoxical gas embolism. We present the anaesthetic management of a patient with patent foramen ovale, Down syndrome and pectus carinatus who successfully underwent laparoscopic Morgagni hernia repair. Under a well-managed anaesthesia that prevented complications because of pneumoperitoneum, laparoscopic surgery would be safe enough for patients with Morgagni hernia having an associated congenital heart disease. PMID- 27366556 TI - Perioperative Management of Severe Hypertension during Laparoscopic Surgery for Pheochromocytoma. AB - Phaeochromocytoma is a catecholamine-secreting vascular tumour that is derived from chromaffin cell. Lethal cardiovascular complications, such as serious hypertension, myocardial infarction and aortic dissection, may occur because of uncontrolled catecholamine release. Each stage of anaesthesia management has vital importance because of this destructive catecholamine secretion that may occur during induction, perioperative stage and surgical manipulation. In this study, we report regarding the preoperative preparation and severe, persistent hypertension attack management with a combination of alpha-adrenergic blockade, beta-adrenergic blockade, sodium nitroprusside and remifentanil in a patient who underwent laparoscopic surgery for phaeochromocytoma. PMID- 27366557 TI - Anaesthesia Application for Cardiac Denervation in a Patient with Long QT Syndrome and Cardiomyopathy. AB - Long QT syndrome is a congenital disorder that is characterized by a prolongation of the QT interval on electrocardiograms and a propensity to ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest or sudden death. Cardiomyopathy and pulmonary hypertension diseases have additional risks in anaesthesia management. In this study, we emphasize on one lung ventilation, pacemaker-implantable cardioverter-defibrillator and the anaesthesia management process in a patient with long QT syndrome, cardiomyopathy and pulmonary hypertension who underwent thoracic sympathectomy. PMID- 27366558 TI - Massive Blood Transfusion during Revision Total Hip Arthroplasty under Combined Spinal Epidural Anaesthesia. AB - Revision total hip arthroplasty (THA) is an orthopaedic surgery that is known to be associated with excessive bleeding. The rates of mortality and morbidity are high in patients with massive haemorrhage. The patient in this study was administered blood products with high fresh frozen plasma/red blood cell (RBC) suspension ratio and high platelet/RBC suspension ratio without waiting for haemostasis test results. This study suggests that this approach might prove beneficial in reducing the incidence of intra- and postoperative complications. this study presents our experience with a patient who underwent THA and required a transfusion that was three times her estimated total blood volume. The patient was successfully managed with close monitoring of haemorrhage and timely administration of blood and blood products before hypotension and loss of consciousness occurred. PMID- 27366559 TI - Ultrasound-Guided Thoracic Paravertebral Block Experience in a Child. PMID- 27366560 TI - Critical Incident Reporting System in Teaching Hospitals in Turkey: A Survey Study. AB - OBJECTIVE: Critical incident reporting systems (CIRS) and morbidity-mortality meetings (MMMs) offer the advantages of identifying potential risks in patients. They are key tools in improving patient safety in healthcare systems by modifying the attitudes of clinicians, nurses and staff (human error) and also the system (human and/or technical error) according to the analysis and the results of incidents. METHODS: One anaesthetist assigned to an administrative and/or teaching position from all university hospitals (UHs) and training and research hospitals (TRHs) of Turkey (n=114) was contacted. In this survey study, we analysed the facilities of anaesthetists in Turkish UHs and TRHs with respect to CIRS and MMMs and also the anaesthetists' knowledge, experience and attitudes regarding CIs. RESULTS: Anaesthetists from 81 of 114 teaching hospitals replied to our survey. Although 96.3% of anaesthetists indicated CI reporting as a necessity, only 37% of departments/hospitals were reported to have CIRS. True definition of CI as "an unexpected /accidental event" was achieved by 23.3% of anaesthetists with CIRS. MMMs were reported in 60.5% of hospitals. Nevertheless, 96% of anaesthetists believe that CIRS and MMMs decrease the incidence of CI occurring. CI occurrence was attributed to human error as 4 [1-5]/10 and 3 [1 5]/10 in UHs and TRHs, respectively (p=0.005). In both hospital types, technical errors were evaluated as 3 [1-5]/10 (p=0.498). CONCLUSION: This first study regarding CIRS in the Turkish anaesthesia departments/hospitals highlights the lack of CI knowledge and CIRS awareness and use in anaesthesia departments/teaching hospitals in Turkey despite a safety reporting system set up by the Turkish Ministry of Health. PMID- 27366561 TI - Intubation of a Paediatric Manikin in Tongue Oedema and Face-to-Face Simulations by Novice Personnel: a Comparison of Glidescope, Airtraq and Direct Laryngoscopy. AB - OBJECTIVE: Glidescope and Airtraq were designed for facilitating intubation and for teaching regarding the airway anatomy. We aimed to evaluate their efficacy in normal airway, tongue oedema and face-to-face orotracheal intubation models when used by novice personnel. METHODS: After the local human research ethics committee approval, 36 medical students who were in the beginning of their third year were enrolled in this study. After watching a video regarding intubation using one of these devices, the students intubated a paediatric manikin with a Glidescope or Airtraq via the normal airway, tongue oedema and face-to-face approach. RESULTS: Although the insertion and intubation times were similar among the groups, the intubation success rate of the Glidescope was higher in the normal airway (100% vs 67%) and tongue oedema (89% vs. 50%) compared with the Airtraq (p=0.008 and p=0.009). The success rates with the paediatric manikin by the face-to-face approach were similar among the groups (50%) (p=0.7). The need for manoeuvres in the Glidescope was lower in the normal and tongue oedema models (p=0.02 and p=0.002). In addition, oesophageal intubation was low in the control and tongue oedema models with the Glidescope (p=0.03 and p<0.001). CONCLUSION: Novice personnel could more easily intubate the trachea with the Glidescope than with the Airtraq. Intubation with the Glidescope was superior to that with the Airtraq in the normal and tongue oedema models. The face-to-face intubation success rates were both low with both the Glidescope and Airtraq groups. PMID- 27366562 TI - Airtraq, LMA CTrach and Macintosh Laryngoscopes in Tracheal Intubation Training: A Randomized Comparative Manikin Study. AB - OBJECTIVE: Training students on simulators before allowing their direct contact with patients is well accepted. There is no clinical or manikin-based simulation study in the literature comparing tracheal intubation with Airtraq, laryngeal mask airway (LMA) CTrach and Macintosh laryngoscopes performed by medical students having no prior intubation experience. METHODS: After obtaining written informed consents, 123 participants were included in the study. The participants were asked to intubate the manikin five times with each device randomly. After all the participants had completed their fifth intubations, the measurements were performed. The primary outcome variables were the first-attempt success rate and the time for a successful intubation, while the secondary outcome variables were to determine the scores of dental trauma, the difficulty visual analogue scale and the optimization manoeuvres. RESULTS: The LMA CTrach group revealed a significantly higher number of intubation attempts. The mean time for a successful intubation was the longest in the LMA CTrach group (17.66+/-8.22 s, p<0.05). Students defined the Airtraq as the easiest to use and the Macintosh laryngoscope as the most difficult device to use and learn. Dental trauma severity was significantly lower in the Airtraq group than in the other groups (p<0.05), and it was found to be 0 in 81.1% in the Airtraq group. The head extension optimization manoeuvre rate was significantly higher with the Macintosh laryngoscope than with the Airtraq laryngoscope (p<0.05). CONCLUSION: This study, in which different types of laryngoscopes were compared, revealed that the Airtraq laryngoscope has advantages, such as shorter intubation duration, less additional optimization manoeuvres, less dental trauma intensity and is easier to learn compared with the LMA CTrach and Macintosh laryngoscopes. PMID- 27366563 TI - Comparing the Laryngeal Mask Airway, Cobra Perilaryngeal Airway and Face Mask in Children Airway Management. AB - OBJECTIVE: We compared the effects of the laryngeal mask airway (LMA), face mask and Cobra perilaryngeal airway (PLA) in the airway management of spontaneously breathing paediatric patients undergoing elective inguinal surgery. METHODS: In this study, 90 cases of 1-14-year-old children undergoing elective inguinal surgery were scheduled. The patients were randomly divided into three groups. Anaesthesia was provided with sevoflurane and 50%-50% nitrous oxide and oxygen. After providing an adequate depth of anaesthesia, supraglottic airway devices were inserted in the group I and II patients. The duration and number of insertion, haemodynamic parameters, plateau and peak inspiratory pressure and positive end-expiratory pressure of the patients were recorded preoperatively, after induction and at 5, 10, 15 and 30 min peroperatively. RESULTS: There were no statistical differences between the groups in terms of haemodynamic parameters (p>0.05). In group II, instrumentation success was higher and instrumentation time was shorter than group II. The positive end-expiratory pressure and plateau and peak inspiratory pressure values were statistically lower in group II (p<0.05). CONCLUSION: We concluded that for airway safety and to avoid possible complications, LMA and Cobra PLA could be alternatives to face mask and that the Cobra PLA provided lower airway pressure and had a faster and more easy placement than LMA. PMID- 27366564 TI - Prevention of Withdrawal Movement Associated with the Injection of Rocuronium in Children: Comparison of Paracetamol and Lidocaine. AB - OBJECTIVE: Pain from rocuronium injection is observed in 50%-80 % of patients. This study aimed to compare the effectiveness of pretreatment with paracetamol and lidocaine in preventing pain-induced withdrawal caused by the intravenous injection of rocuronium during the induction of general anaesthesia in paediatric patients. METHODS: Ninety children were randomized into two groups using a simple drawing from the box method: a paracetamol group (Group P, n=45) and a lidocaine group (Group L, n=45). After anaesthesia induction, venous occlusion was applied by a paediatric cuff inflated to a pressure of 75 mmHg and by 50 mg paracetamol and 0.5 mg kg(-1) lidocaine was injected in Groups P and L, respectively. Venous occlusion was then released, followed by rocuronium injection (0.6 mg kg(-1)). Withdrawal was evaluated using a 4-point scale (1, no response; 2, movement at the wrist only; 3, movement/withdrawal involving arm only (elbow/shoulder) and 4, generalized response, movement/withdrawal in more than one extremity). RESULTS: The incidence of withdrawal movement was 42% and 26% in the Groups P and L, respectively (p=0.120). Although no significant differences were noted in the number of patients who had no withdrawal movement and mild withdrawal movement in Groups P and L, compared with Group L, the incidences of moderate withdrawal movement were significantly higher in Group P (p<0.05). No patient in either group revealed generalized movement. CONCLUSION: Using a venous occlusion technique, pretreatment with 50 mg paracetamol can prevent withdrawal movement caused by rocuronium injection in children but is not as effective as lidocaine to prevent moderate withdrawal movement. PMID- 27366565 TI - The Efficacy of Femoral Block and Unilateral Spinal Anaesthesia on Analgesia, Haemodynamics and Mobilization in Patients undergoing Endovenous Ablation in the Lower Extremity. AB - OBJECTIVE: This study aimed to investigate the efficacy of femoral block and unilateral spinal anaesthesia on analgesia, haemodynamics and mobilization during endovenous ablation in patients with lower extremity venous insufficiency. METHODS: Forty patients of ASA physical status I and II, with ages ranging between 30 and 45 years, and who were scheduled for endovenous laser ablation for varicose veins were prospectively enrolled in this study. Patients were randomized into a unilateral spinal anaesthesia group (group HS, n=20) or a femoral block group (group F, n=20). Group HS received 7.5-10 mg of heavy bupivacaine for unilateral spinal anaesthesia, while group F received 100 mg prilocaine for femoral block with ultrasound guidance. The level of motor blockage (Bromage score), visual pain score, mean heart rate and mean arterial pressures were recorded at postoperative 0, 1, 2, 3d and 6 h, respectively. RESULTS: Perioperative visual pain score values in both groups were <4. None of the groups required an additional analgesic agent. Bromage scores were significantly lower in group F than in group HS during the postoperative period (p<0.01). Motor function returned to normal in all patients at 3 h in group F and at 6 h in group HS. Postoperative mean heart rate and arterial pressure did not differ between the groups (p>0.05). CONCLUSION: In patients with lower extremity venous insufficiency who were undergoing endovenous laser ablation, an ultrasound guided femoral block provided similar analgesia with that of unilateral spinal anaesthesia. In group F, the duration of anaesthesia and mobilization time was shorter. PMID- 27366566 TI - Anaesthetic Management of a Patient with Brugada Syndrome. AB - Brugada Syndrome is a condition with an undetermined aetiology and a tendency for malignant arrhythmias, an electrocardiographic pattern of a right bundle branch block with persistent ST segment elevation in the right precordial leads (V1-V3) and no association with structural heart disease. We aimed to discuss the anaesthetic management of an asymptomatic 35-year-old patient with Brugada syndrome who had been diagnosed during the pre-anaesthetic assessment because of the family history of the early sudden cardiac death of his mother. As a result, we believe that detailed patient history and careful examination of laboratory tests and electrocardiography are crucial for early diagnosis of some diseases and for successful anaesthetic management. PMID- 27366567 TI - Sugammadex in a Patient with Brugada Syndrome. AB - Brugada Syndrome was first described in 1992 by Pedro Brugada as a genetic syndrome that is characterized by ventricular arrhythmias that may result in sudden cardiac arrest. In particular, a right bundle branch block and ST segment elevation in the right precordial leads are observed. Many perioperative pharmalogical and physiological factors can trigger malignant arrhythmias. Although it is a rare condition, the anaesthestic management of Brugada syndrome is important because of the potentially fatal complications. Many anaesthetics have been administered during the operation of patients with Brugada Syndrome. The use of sugammadex instead of the anaesthetic management of patients with Brugada syndrome is discussed in this study. PMID- 27366568 TI - Safe Anaesthesia Management in a Child with Congenital Long QT Syndrome. AB - Long QT syndrome is a cardiac repolarisation disorder that can occur with clinical symptoms such as dizziness, fainting, life-threatening arrhythmias and sudden cardiac death, and its incidence is increasing in the general population. A careful anaesthetic management is required for patients with this syndrome because of the risk of torsades de pointes and malignant arrhythmias. In this case report, we discuss the anaesthetic management of a seven-year-old patient with congenital long QT syndrome that was diagnosed during the preoperative evaluation. PMID- 27366569 TI - Anaesthetic Management for Appendectomy in a Patient with Situs Inversus Totalis. AB - Situs inversus totalis is a congenital syndrome, in which all the internal organs are in the opposite position, including dextrokardia. Most patients are asymptomatic and maintain their normal life. Kartagener syndrome may accompany situs inversus totalis. Diagnosis may be overlooked in patients with situs inversus totalis in emergency situations. Patients with this syndrome should inform the clinician as this will facilitate the diagnosis. Acute appendicitis is an emergency situation that would require urgent intervention. Appendicitis symptoms can be observed in the left lower quadrant of patients. We present a case concerning the anaesthetic management of a patient with situs inversus undergoing an emergency appendectomy. PMID- 27366570 TI - Postoperative Respiratory Failure in a Patient with Undiagnosed Myastenia Gravis. AB - Myasthenia gravis (MG) is an autoimmune disease caused by the development of antibodies against the nicotinic acetylcholine receptor. There is hypersensitivity against non-depolarizing muscle relaxants in these patients. Sugammadex eliminates the effects of steroid non-depolarizing muscle relaxants, such as rocuronium and vecuronium, by selectively encapsulating their molecules. In this case report, we present a case of recurarization and respiratory failure after the use of sugammadex and rocuronium in a patient with preoperatively undiagnosed myasthenia gravis. PMID- 27366571 TI - Whole Lung Lavage in a Pulmonary Alveolar Proteinosis Patient with Severe Respiratory Failure. AB - Pulmonary alveolar proteinosis (PAP) is a rare interstitial lung disease that develops as a result of defects in the clearance of surfactant by alveolar macrophages. The accumulation of lipid- and protein-rich substances in the alveoli constitutes the main pathology of this disease. PAP has three types of aetiology: autoimmune (primary), congenital and secondary. The most common form in adults is autoimmune PAP. Whole lung lavage is a commonly performed method for treatment of this form of disease, especially in more severe cases. Performed under general anaesthesia, the material deposited in the alveoli is removed by washing. In this paper, we present a whole lung lavage under anaesthesia in a PAP patient who had severe respiratory failure. PMID- 27366572 TI - Successful Anaesthetic Management of Elderly Patients with Leprosy. PMID- 27366573 TI - The Influence of Oral Carbohydrate Solution Intake on Stress Response before Total Hip Replacement Surgery during Epidural and General Anaesthesia. AB - OBJECTIVE: The effects of oral carbohydrate solutions, ingested 2 h prior to operation, on stress response were studied in patients undergoing general or epidural anaesthesia. METHODS: The study was performed on 80 ASA I-II adult patients undergoing elective total hip replacement, which were randomized to four groups (n=20). Group G patients undergoing general anaesthesia fasted for 8 h preoperatively; Group GN patients undergoing general anaesthesia drank oral carbohydrate solutions preoperatively; Group E patients undergoing epidural anaesthesia fasted for 8 h and Group EN patients undergoing epidural anaesthesia drank oral carbohydrate solutions preoperatively. Groups GN and EN drank 800 mL of 12.5% oral carbohydrate solution at 24:00 preoperatively and 400 mL 2 h before the operation. Blood samples were taken for measurements of glucose, insulin, cortisol and IL-6 levels. RESULTS: The effect of preoperative oral carbohydrate ingestion on blood glucose levels was not significant. Insulin levels 24 h prior to surgery were similar; however, insulin levels measured just before surgery were 2-3 times higher in groups GN and EN than in groups G and E. Insulin levels at the 24(th) postoperative hour in epidural groups were increased compared to those at basal levels, although general anaesthesia groups showed a decrease. From these measurements, only the change in Group EN was statistically significant (p<0.05). Plasma cortisol levels at the 2(nd) peroperative hour were higher in epidural groups than in general anaesthesia groups. Both anaesthesia techniques did not have an effect on IL-6 levels. CONCLUSION: We concluded that epidural anaesthesia suppressed stress response, although preoperative oral carbohydrate nutrition did not reveal a significant effect on surgical stress response. PMID- 27366574 TI - Do Urgent Caesarean Sections Have a Circadian Rhythm? AB - OBJECTIVE: The primary goal of the present study was to demonstrate the existence of a possible circadian variation in urgent operative deliveries. METHODS: All urgent caesarean sections between 1 January 2014 and 1 January 2015 with known exact onset times of operation were included in this retrospective study. Cases that were previously scheduled for elective caesarean section were excluded. Information regarding age, delivery date, onset time of operation and type of anaesthesia was collected from the database. Analyses were completed using the Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, USA) version 20.0 software. The statistical significance for all analyses was set at p<0.05. RESULTS: A total of 285 urgent caesarean section deliveries were included in the study. There were 126 (44.2%) deliveries during the day shift and 159 (55.8%) during the night shift. 80 patients (28.1%) received general anaesthesia and 65 (22.8%) received spinal anaesthesia in the morning shift, whereas 54 patients (18.9%) received general anaesthesia and 86 (30.2%) received spinal anaesthesia during the night shift. CONCLUSION: The present study suggested that urgent caesarean sections revealed a circadian rhythm during the day. PMID- 27366575 TI - Postperfusion Syndrome in Cadaveric Liver Transplantations: A Retrospective Study. AB - OBJECTIVE: To evaluate the factors that affects the postperfusion syndrome in cadaveric liver transplantations and the effect of the postperfusion syndrome on discharge from the hospital. METHODS: Patients who underwent cadaveric liver transplantations between 2007 and 2013 were scanned retrospectively. Intraoperative anaesthesia records, intensive care unit follow-up forms and discharge reports were examined from patient files. Overall, 43 patients having complete data were included in the study. The postperfusion syndrome is defined as asystoli or a decrease in mean arterial pressure of more than 30%, which occurred in the first 5 min of reperfusion and continued for 1 min. Patients were divided into two groups: those who had the postperfusion syndrome and those who did not. RESULTS: The number of patients who had the postperfusion syndrome was 25 of 43 (58.1%). The MELD score of patients without the postperfusion syndrome was calculated as 16.9+/-3.2 and that of patients with the postperfusion syndrome was 19.7+/-3.6. A statistically significant relationship was detected between the postperfusion syndrome occurrence and a high MELD score (p=0.013). The diastolic blood pressure just before reperfusion was statistically lower in the group with the postperfusion syndrome than in the other group (p=0.023, 50+/-8 vs. 58+/-11). According to the logistic regression analysis, the MELD score and the decrease in diastolic blood pressure before reperfusion were defined as independent predictive factors. CONCLUSION: According to the study, the ratio for having the postperfusion syndrome was found to be 58.1%. The independent predictor factors affecting the postperfusion syndrome were detected as the MELD score and the decrease in diastolic blood pressure before reperfusion. The postperfusion syndrome during orthotropic liver transplantation is an important issue for anaesthesiologists. The awareness of the related factors with the postperfusion syndrome may help in the development of various preventive strategies. PMID- 27366577 TI - Attitudes of Doctors Working in Abant Izzet Baysal University Health Research and Application Center on Cardiopulmonary Resuscitation. AB - OBJECTIVE: We aimed to evaluate the attitudes of doctors about cardiopulmonary resuscitation (CPR) in this research. METHODS: Overall, 234 doctors who were working in Abant Izzet Baysal University Health Research and Application Center and who accepted to participate in this research were included. Research data were obtained by a questionnaire containing questions about demographic characteristics of doctors and their knowledge about CPR. Questionnaires were applied between 27.02.2012 and 04.06.2012. The chi-square test was used for categorical variables. A value of p<0.05 was considered statistically significant. RESULTS: It was determined that 90% of the participants included in the study applied and/or observed CPR, and 62% of participants did not attend any CPR course. In addition, 64.1% of the doctors were found to be aware of guidelines prepared every 5 years. Although 65.2% of the doctors who attended a course previously gave a correct answer for the question about the number of cardiac compressions during adult CPR, 47.6% of the doctors who did not attend a course gave the correct answer (p=0.014). Additionally, 71.9% of participants who attended a course previously and 51.7% of participants who did not replied correctly to the question 'What should be done immediately after defibrillation during CPR?' And also the results for the question about how many joules is necessary to begin defibrillation with a monophasic defibrillator were statistically significant according to the attendance for a CPR course (p<0.005). CONCLUSION: In this study, we have identified the lack of knowledge of the doctors about resuscitation. PMID- 27366576 TI - Evaluation of the Approaches of the Anaesthesiologists on Maintenance of Anaesthesia Machines. AB - OBJECTIVE: In this study, we aimed to discuss the level of knowledge and approach on 'maintenance, calibration and cleaning of anaesthesia devices' among anaesthesiologists in Turkey. METHODS: A questionnaire was prepared with 21 questions based on the Google document system, and these questionnaires were sent to the anaesthesiologists via e-mail. RESULTS: Overall, 226 anaesthesiologists answered our survey. With respect to the maintenance and calibration, anaesthesiologists had sufficient information about the vaporizer and the carbon dioxide canister devices; however, information about the vital components, such as disassembly of the anaesthesia machine, flow sensor, oxygen sensor, battery and exhaust system, was insufficient. The cleaning and sterilization procedures were performed when the devices became dirty, and the bacteria filter was used only for the protection of the anaesthesia system. There was a lack of knowledge about how and which part of the anaesthesia device should be disinfected. In total, 85% of the survey participants were thinking of the need of additional education on anaesthesia machine maintenance. CONCLUSION: It is observed that education about anaesthesia device maintenance, calibration and cleaning issues is obviously necessary for the anaesthesiology specialists in our country. We believe that it would be useful to highlight this issue to anaesthesia educational institutions and anaesthesia associations. PMID- 27366578 TI - Anaesthesia Management of a Patient with Factor XI Deficiency. AB - Factor XI deficiency is an extremely rare disease presenting no clinical symptoms, unless there is an inducing reason such as trauma or surgery. Normally, factor levels are in the range of 70-150 U dL-1 in healthy subjects. Although no clinical symptoms are seen, only high levels of aPTT can be found. Once a prolongation is detected in aPTT, factor XI deficiency should be suspected and factor levels should be analysed. With careful preoperative preparations in factor-deficient people, preoperative and postoperative complications can be decreased. In this case report, management of anaesthesia during total hip arthroplasty of a patient with factor XI deficiency is presented. PMID- 27366579 TI - Anaesthetic Management of Children with Rubinstein-Taybi Syndrome. AB - Rubinstein-Taybi syndrome (RTS) is a rare, autosomal dominant syndrome presenting with mental retardation and physical abnormalities, including broad thumbs, big and broad toes, short stature and craniofacial anomalies. Special attention was paid to the possibilities of difficult airway, aspiration pneumonia and cardiovascular dysfunction during anaesthesia. Micrognathia, retrognathia, broad nasal bridge, abnormally large or 'beak-shaped' nose, hypoplastic maxilla and small mouth-typical dysmorphic facial features are one of the biggest causes of the difficult airway in this syndrome. Approximately one-third of the affected individuals have a variety of congenital heart diseases. Recurrent respiratory infections are likely to be the result of microaspiration or gastro-oesophageal reflux in this syndrome. In this case report, we discussed the anaesthesia management of a child with RTS who underwent right endoscopic dacryocystorhinostomy. PMID- 27366580 TI - Unexpected Difficulties in Intubation: Undiagnosed Subglottic Stenosis. PMID- 27366581 TI - Anaesthesia Management for Edward's Syndrome (Trisomy 18). PMID- 27366582 TI - A Forgotten but Important Drug on Preanaesthetic Evaluation: Amiodarone. PMID- 27366583 TI - Knowledge, Attitude and Perception of Ebola Virus Disease among Secondary School Students in Ondo State, Nigeria, October, 2014. AB - INTRODUCTION: The first case of Ebola Virus Disease (EVD) in Nigeria was imported on 20th July 2014, by an air traveller. On 8th August, 2014, WHO declared the Ebola outbreak in West Africa a Public Health Emergency of International Concern (PHEIC). This study aimed at assessing the knowledge, perception and attitude of secondary school students towards EVD and adopting disease preventive behaviour. METHODS: A descriptive cross sectional study of 440 students from a mixed secondary school in Owo, Ondo State was done. Data was collected in October 2014 when Nigeria was yet to be declared EVD free.Simple random sampling was used to select the school while Systematic random sampling was used in the selection of participants. A semi-structured, interviewer administered questionnaire was used to collect data. Data was analyzed with SPSS version 21. Descriptive statistics and Chi-square test were done, level of statistical significant was 5%. RESULTS: Mean age of respondents was 13.7+/-1.9 years. Females were 48.2%. Most of the respondents had heard of Ebola Virus Disease (95.4%). Female respondents (51.3%), those who were 15 years and above (51.1%) and in the senior class (54.1%), and had good general knowledge of EVD and across all domains. Being in the senior secondary class and seeking for health care in the hospital were positively associated with good general knowledge (p-value: 0.029, and <0.001 respectively). Three commonest modes of spread of EVD mentioned were contact between infected animals and men (74.8%), touching body fluids of a person who is sick of EVD (57.0%), and contact (55.2%). The top three signs of EVD mentioned were abnormal bleeding from any part of the body (56.10%), vomiting (47.0%) and fever (42.3%). CONCLUSION: Our results revealed suboptimal EVD-related knowledge, attitude and practice among the students. Promotion of health messages and training of students on prevention of EVD to effectively control past and future outbreaks of EVD in Nigeria was immediately initiated in schools in Ondo State. PMID- 27366584 TI - If Numbers Can Speak, Who Listens? Creating Engagement and Learning for Effective Uptake of DRR Investment in Developing Countries. AB - INTRODUCTION: With a renewed emphasis on evidence-based risk sensitive investment promoted under the Sendai Framework for Disaster Risk Reduction 2015-2030, technical demands for analytical tools such as probabilistic cost-benefit analysis (CBA) will likely increase in the foreseeable future. This begs a number of pragmatic questions such as whether or not sophisticated quantitative appraisal tools are effective in raising policy awareness and what alternatives are available. METHOD: This article briefly reviews current practices of analytical tools such as probabilistic cost-benefit analysis and identifies issues associated with its applications in small scale community based DRR interventions. RESULTS: The article illustrate that while best scientific knowledge should inform policy and practice in principle, it should not create an unrealistic expectation that the state-of-the art methods must be used in all cases, especially for small scale DRR interventions in developing countries, where data and resource limitations and uncertainty are high, and complex interaction and feedback may exist between DRR investment, community response and longer-term development outcome. DISCUSSION: Alternative and more participatory approaches for DRR appraisals are suggested which includes participatory serious games that are increasingly being used to raise awareness and identify pragmatic strategies for change that are needed to bring about successful uptake of DRR investment and implementation of DRR mainstreaming. PMID- 27366585 TI - Genetically Modified (GM) Mosquito Use to Reduce Mosquito-Transmitted Disease in the US: A Community Opinion Survey. AB - INTRODUCTION: Mosquito-borne infectious diseases such as dengue, chikungunya, and now Zika, pose a public health threat to the US, particularly Florida, the Gulf Coast states, and Hawaii. Recent autochthonous transmission of dengue and chikungunya in Florida, the recent dengue outbreak in Hawaii, and the potential for future local spread of Zika in the US, has led to the consideration of novel approaches to mosquito management. One such novel approach, the release of sterile genetically modified mosquitoes, has been proposed as a possible intervention, and a trial release of GM mosquitoes is being considered in one Florida community. However, this proposal has been controversial. The objective of this research was to increase understanding of community knowledge, attitudes, and beliefs regarding mosquito control and GM mosquitoes. METHODS: An 18 question self-administered survey was mailed to all households in the identified Key West, Florida neighborhood where a GM mosquito trial has been proposed. This survey was fielded between July 20, 2015 and November 1, 2015. The main outcome variable was opposition to the use of GM mosquitoes. Measures included demographic information and opinions on mosquitoes, mosquito control, and vector borne diseases. RESULTS: A majority of survey respondents did not support use of GM mosquitoes as a mosquito control method. DISCUSSION: Reasons for opposition included general fears about possible harmful impacts of this intervention, specific worries about human and animal health impacts from the GM mosquitoes, and environmental concerns about potential negative effects on the ecosystem. Residents were more likely to oppose GM mosquito use if they had a low perception of the potential risks posed by diseases like dengue and chikungunya, if they were female, and if they were less concerned about the need to control mosquitoes in general. These findings suggest a need for new approaches to risk communication, including educational efforts surrounding mosquito control and reciprocal dialogue between residents and public health officials. PMID- 27366586 TI - Using Phenomenological Models to Characterize Transmissibility and Forecast Patterns and Final Burden of Zika Epidemics. AB - BACKGROUND: The World Health Organization declared the ongoing Zika virus (ZIKV) epidemic in the Americas a Public Health Emergency of International Concern on February 1, 2016. ZIKV disease in humans is characterized by a "dengue-like" syndrome including febrile illness and rash. However, ZIKV infection in early pregnancy has been associated with severe birth defects, including microcephaly and other developmental issues. Mechanistic models of disease transmission can be used to forecast trajectories and likely disease burden but are currently hampered by substantial uncertainty on the epidemiology of the disease (e.g., the role of asymptomatic transmission, generation interval, incubation period, and key drivers). When insight is limited, phenomenological models provide a starting point for estimation of key transmission parameters, such as the reproduction number, and forecasts of epidemic impact. METHODS: We obtained daily counts of suspected Zika cases by date of symptoms onset from the Secretary of Health of Antioquia, Colombia during January-April 2016. We calibrated the generalized Richards model, a phenomenological model that accommodates a variety of early exponential and sub-exponential growth kinetics, against the early epidemic trajectory and generated predictions of epidemic size. The reproduction number was estimated by applying the renewal equation to incident cases simulated from the fitted generalized-growth model and assuming gamma or exponentially distributed generation intervals derived from the literature. We estimated the reproduction number for an increasing duration of the epidemic growth phase. RESULTS: The reproduction number rapidly declined from 10.3 (95% CI: 8.3, 12.4) in the first disease generation to 2.2 (95% CI: 1.9, 2.8) in the second disease generation, assuming a gamma-distributed generation interval with the mean of 14 days and standard deviation of 2 days. The generalized-Richards model outperformed the logistic growth model and provided forecasts within 22% of the actual epidemic size based on an assessment 30 days into the epidemic, with the epidemic peaking on day 36. CONCLUSION: Phenomenological models represent promising tools to generate early forecasts of epidemic impact particularly in the context of substantial uncertainty in epidemiological parameters. Our findings underscore the need to treat the reproduction number as a dynamic quantity even during the early growth phase, and emphasize the sensitivity of reproduction number estimates to assumptions on the generation interval distribution. PMID- 27366587 TI - FLIRT-ing with Zika: A Web Application to Predict the Movement of Infected Travelers Validated Against the Current Zika Virus Epidemic. AB - INTRODUCTION: Beginning in 2015, Zika virus rapidly spread throughout the Americas and has been linked to neurological and autoimmune diseases in adults and babies. Developing accurate tools to anticipate Zika spread is one of the first steps to mitigate further spread of the disease. When combined, air traffic data and network simulations can be used to create tools to predict where infectious disease may spread to and aid in the prevention of infectious diseases. Specific goals were to: 1) predict where travelers infected with the Zika Virus would arrive in the U.S.; and, 2) analyze and validate the open access web application's (i.e., FLIRT) predictions using data collected after the prediction was made. METHOD: FLIRT was built to predict the flow and likely destinations of infected travelers through the air travel network. FLIRT uses a database of flight schedules from over 800 airlines, and can display direct flight traffic and perform passenger simulations between selected airports. FLIRT was used to analyze flights departing from five selected airports in locations where sustained Zika Virus transmission was occurring. FLIRT's predictions were validated against Zika cases arriving in the U.S. from selected airports during the selected time periods. Kendall's tau and Generalized Linear Models were computed for all permutations of FLIRT and case data to test the accuracy of FLIRT's predictions. RESULTS: FLIRT was found to be predictive of the final destinations of infected travelers in the U.S. from areas with ongoing transmission of Zika in the Americas from 01 February 2016 - 01 to April 2016, and 11 January 2016 to 11 March 2016 time periods. MIA-FLL, JFK-EWR-LGA, and IAH were top ranked at-risk metro areas, and Florida, Texas and New York were top ranked states at-risk for the future time period analyzed (11 March 2016 - 11 June 2016). For the 11 January 2016 to 11 March 2016 time period, the region aggregated model indicated 7.24 (95% CI 6.85 - 7.62) imported Zika cases per 100,000 passengers, and the state-aggregated model suggested 11.33 (95% CI 10.80 11.90) imported Zika cases per 100,000 passengers. DISCUSSION: The results from 01 February 2016 to 01 April 2016 and 11 January 2016 to 11 March 2016 time periods support that modeling air travel and passenger movement can be a powerful tool in predicting where infectious diseases will spread next. As FLIRT was shown to significantly predict distribution of Zika Virus cases in the past, there should be heightened biosurveillance and educational campaigns to medical service providers and the general public in these states, especially in the large metropolitan areas. PMID- 27366588 TI - Igg Subclasses Targeting the Flagella of Salmonella enterica Serovar Typhimurium Can Mediate Phagocytosis and Bacterial Killing. AB - Invasive non-typhoidal Salmonella are a common cause of invasive disease in immuno-compromised individuals and in children. Multi-drug resistance poses challenges to disease control, with a critical need for effective vaccines. Flagellin is an attractive vaccine candidate due to surface exposure and high epitope copy number, but its potential as a target for opsonophacytic antibodies is unclear. We examined the effect of targeting flagella with different classes of IgG on the interaction between Salmonella Typhimurium and a human phagocyte like cell line, THP-1. We tagged the FliC flagellar protein with a foreign CD52 mimotope (TSSPSAD) and bacteria were opsonized with a panel of humanised CD52 antibodies with the same antigen-binding V-region, but different constant regions. We found that IgG binding to flagella increases bacterial phagocytosis and reduces viable intracellular bacterial numbers. Opsonisation with IgG3, followed by IgG1, IgG4, and IgG2, resulted in the highest level of bacterial uptake and in the highest reduction in the intracellular load of viable bacteria. Taken together, our data provide proof-of-principle evidence that targeting flagella with antibodies can increase the antibacterial function of host cells, with IgG3 being the most potent subclass. These data will assist the rational design of urgently needed, optimised vaccines against iNTS disease. PMID- 27366589 TI - A Predictive Model for Diabetic Foot Ulcer Outcome: The Wound Healing Index. AB - Objective: To develop a healing index for patients with diabetic foot ulcers (DFUs) for use in clinical practice, research analysis, and clinical trials. Approach: U.S. Wound Registry data were examined retrospectively and assigned a clear outcome (healed, amputated, etc.). Significant variables were identified with bivariate analyses. A multivariable logistic regression model was created based on significant factors (p < 0.05) and tested on a hold-out sample of data. Out of 13,266 DFUs from the original dataset, 6,440 were eligible for analysis. The logistic regression model included 5,239 ulcers, of which 3,462 healed (66.1%). The 10% validation sample utilized 555 ulcers, of which 377 healed (67.9%). Results: Variables that significantly predicted healing were as follows: wound age (duration in days), wound size, number of concurrent wounds of any etiology, evidence of bioburden/infection, patient age, Wagner grade, being nonambulatory, renal dialysis, renal transplant, peripheral vascular disease, and patient hospitalization for any reason. Innovation: We present a validated stratification system, previously described as the Wound Healing Index (WHI), which predicts healing likelihood of patients with DFUs, incorporating patient- and wound-specific variables. Conclusion: The DFU WHI is a comprehensive and user friendly validated predictive model for DFU healing. It can risk stratify patients enrolled in clinical research trials, stratify patient data for quality reporting and benchmarking activities, and identify patients most likely to require costly therapy to heal. PMID- 27366590 TI - Adipose-Derived Regenerative Cell Therapy for Burn Wound Healing: A Comparison of Two Delivery Methods. AB - Objective: The use of noncultured autologous stromal vascular fraction or clinical grade adipose-derived regenerative cells (ADRCs) is a promising strategy to promote wound healing and tissue repair. Nevertheless, issues regarding the optimal mode of administration remain unclear. The purpose of this study was to compare the effects of local injection and topical spray delivery of ADRCs in a porcine model of thermal burns. Approach: Full-thickness thermal burns were created on the dorsum of 10 Gottingen minipigs. Two days following injury, wounds underwent fascial excision and were randomized to receive control vehicle or freshly isolated autologous ADRCs delivered by either multiple injections into or surrounding the wound bed, or by spray onto the wound surface (0.25 * 106 viable cells/cm2). Healing was evaluated by planimetry, histopathology, and immunohistochemistry at day 7, 12, 16, 21, and 28 posttreatment. Results:In vitro analysis demonstrated that there was no substantial loss of cell number or viability attributable to the spray procedure. Planimetric assessment revealed that delivery of ADRCs by either local injection or topical spray increased wound reepithelialization relative to control at day 14. No significant difference in wound reepithelialization was observed between both delivery approaches. In addition, on day 7 posttreatment, blood vessel density was greater in wounds receiving local or topical spray ADRCs than in the wounds treated with vehicle control. Histopathologic analysis suggests that ADRC treatment may modulate the inflammatory response by reducing neutrophil infiltration at day 7 and 12 posttreatment, irrespective of the route of administration. Conclusions: These data demonstrate that local injection and spray delivery of ADRCs modulate inflammation and improve wound angiogenesis and epithelialization. Importantly, both delivery routes exhibited similar effects on wound healing. Given the greater ease-of-use associated with topical spray delivery, these data support the use of a spray system for autologous ADRC delivery. PMID- 27366591 TI - A Novel Nude Mouse Model of Hypertrophic Scarring Using Scratched Full Thickness Human Skin Grafts. AB - Objective: Hypertrophic scar (HTS) is a dermal form of fibroproliferative disorder that develops following deep skin injury. HTS can cause deformities, functional disabilities, and aesthetic disfigurements. The pathophysiology of HTS is not understood due to, in part, the lack of an ideal animal model. We hypothesize that human skin with deep dermal wounds grafted onto athymic nude mice will develop a scar similar to HTS. Our aim is to develop a representative animal model of human HTS. Approach: Thirty-six nude mice were grafted with full thickness human skin with deep dermal scratch wound before or 2 weeks after grafting or without scratch. The scratch on the human skin grafts was made using a specially designed jig that creates a wound >0.6 mm in depth. The xenografts were morphologically analyzed by digital photography. Mice were euthanized at 1, 2, and 3 months postoperatively for histology and immunohistochemistry analysis. Results: The mice developed raised and firm scars in the scratched xenografts with more contraction, increased infiltration of macrophage, and myofibroblasts compared to the xenografts without deep dermal scratch wound. Scar thickness and collagen bundle orientation and morphology resembled HTS. The fibrotic scars in the wounded human skin were morphologically and histologically similar to HTS, and human skin epithelial cells persisted in the remodeling tissues for 1 year postengraftment. Innovation and Conclusions: Deep dermal injury in human skin retains its profibrotic nature after transplantation, affording a novel model for the assessment of therapies for the treatment of human fibroproliferative disorders of the skin. PMID- 27366592 TI - Regenerative Medicine: Charting a New Course in Wound Healing. AB - Significance: Chronic wounds are a prevalent and costly problem in the United States. Improved treatments are needed to heal these wounds and prevent serious complications such as infection and amputation. Recent Advances: In wound healing, as in other areas of medicine, technologies that have the potential to regenerate as opposed to repair tissue are gaining ground. These include customizable nanofiber matrices incorporating novel materials; a variety of autologous and allogeneic cell types at various stages of differentiation (e.g., pluripotent, terminally differentiated); peptides; proteins; small molecules; RNA inhibitors; and gene therapies. Critical Issues: Wound healing is a logical target for regenerative medicine due to the accessibility and structure of skin, the regenerative nature of healing, the lack of good limb salvage treatments, and the current use of cell therapies. However, more extensive knowledge of pathophysiologic targets is needed to inform regenerative strategies, and new technologies must demonstrate value in terms of outcomes and related health economic measures to achieve successful market access and penetration. Future Directions: Due to similarities in cell pathways and developmental mechanisms, regenerative technologies developed in one therapeutic area may be applicable to others. Approaches that proceed from human genomic or other big data sources to models are becoming increasingly common and will likely suggest novel therapeutic avenues. To fully capitalize on the advances in regenerative medicine, studies must demonstrate the value of new therapies in identified patient populations, and sponsors must work with regulatory agencies to develop appropriate dossiers supporting timely approval. PMID- 27366593 TI - p27(KIP1) and PTEN cooperate in myeloproliferative neoplasm tumor suppression in mice. AB - PTEN acts as a phosphatase for PIP3 and negatively regulates the PI3K/AKT pathway, and p27(KIP1) is a cyclin-dependent kinase inhibitor that regulates the G1 to S-phase transition by binding to and regulating the activity of cyclin dependent kinases. Genetic alterations of PTEN or CDKN1B (p27(KIP1)) are common in hematological malignancies. To better understand how mutations in these two genes might cooperate in leukemogenesis, we inactivated both genes in the hematological compartment in mice. Here, we show that the combined inactivation of Pten and Cdkn1b results in a more severe myeloproliferative neoplasm phenotype associated with lower hemoglobin, enlarged spleen and liver, and shorter lifespan compared to inactivation of Pten alone. More severe anemia and increased myeloid infiltration and destruction of the spleen contributed to the earlier death of these mice, and elevated p-AKT, cyclin D1, and cyclin D3 might contribute to the development of this phenotype. In conclusion, PTEN and p27(KIP1) cooperate in tumor suppression in the hematological compartment. PMID- 27366594 TI - Fundamental Parameters Line Profile Fitting in Laboratory Diffractometers. AB - The fundamental parameters approach to line profile fitting uses physically based models to generate the line profile shapes. Fundamental parameters profile fitting (FPPF) has been used to synthesize and fit data from both parallel beam and divergent beam diffractometers. The refined parameters are determined by the diffractometer configuration. In a divergent beam diffractometer these include the angular aperture of the divergence slit, the width and axial length of the receiving slit, the angular apertures of the axial Soller slits, the length and projected width of the x-ray source, the absorption coefficient and axial length of the sample. In a parallel beam system the principal parameters are the angular aperture of the equatorial analyser/Soller slits and the angular apertures of the axial Soller slits. The presence of a monochromator in the beam path is normally accommodated by modifying the wavelength spectrum and/or by changing one or more of the axial divergence parameters. Flat analyzer crystals have been incorporated into FPPF as a Lorentzian shaped angular acceptance function. One of the intrinsic benefits of the fundamental parameters approach is its adaptability any laboratory diffractometer. Good fits can normally be obtained over the whole 20 range without refinement using the known properties of the diffractometer, such as the slit sizes and diffractometer radius, and emission profile. PMID- 27366595 TI - Polycapillary Optics for Materials Science Studies: Instrumental Effects and Their Correction. AB - The instrumental effects related to the use of a polycapillary x-ray lens as primary beam collimator are here studied and the features observed in the measurements modelled via Monte-Carlo ray-tracing. Comparison with existing procedures is presented and experimental evidence of the accuracy improvements due to the use of a correction algorithm is shown. PMID- 27366596 TI - Direct Space Structure Solution Applications. AB - The crystal structures of 2,4,6-triisopropylbenzenesulfonamide, 1,2,3 trihydroxybenzene-hexamethylenetetramine (1/1), 5-bromonicotinic acid and chlorothalonil form II have been solved from x-ray powder diffraction data, by application of a direct space structure solution approach using the Monte Carlo method and confirmed by Rietveld refinement. In the sulfonamide, the molecules are linked by N-H?O hydrogen bonds into two-dimensional sheets built from alternating eight and twenty-membered rings. In the cocrystal, the molecules are linked by O-H?N hydrogen bonds to form puckered molecular ribbons that are in turn linked into a continuous 3D framework by C-H?pi (arene) interactions. 5 bromonicotinic acid also displays atypical hydrogen-bonding behaviour by formation of dimers through a self-complementary acid-acid hydrogen-bond motif that are connected into antiparallel ribbons by C-H?O and C-H?N hydrogen bonds. Structure determination of the cocrystal and the bromonicotinic acid was successful despite the presence of preferred orientation in the data, whereas the distortion of the chlorothalonil data was so severe that structure solution was only possible when the effects of preferred orientation were minimized. Both the disordered structure, and an ordered structural approximation of chlorothalonil form II have been determined and rationalized. PMID- 27366597 TI - Diffraction Line Broadening Analysis if Broadening Is Caused by Both Dislocations and Limited Crystallite Size. AB - The determination of dislocation distribution parameters is discussed for specimens where both strain broadening caused by dislocations and size broadening occur. If the strain broadening is well described by a model due to Wilkens, several methods are possible for the analysis of the broadening of diffraction lines. In sputter deposited nickel layers, three different methods for diffraction line broadening analysis yield identical results. The recrystallization of the nickel layers was investigated by annealing the layers at various temperatures in the range 300 K to 500 K. With increasing annealing temperature, the microstructure of the layers changed from a microstructure with small grains and high dislocation density, via a microstructure that is a mixture of small grains with high dislocation density and large grains with low dislocation density, to a microstructure with large grains and low dislocation density. PMID- 27366599 TI - Multidataset Refinement Resonant Diffraction, and Magnetic Structures. AB - The scope of Rietveld and other powder diffraction refinements continues to expand, driven by improvements in instrumentation, methodology and software. This will be illustrated by examples from our research in recent years. Multidataset refinement is now commonplace; the datasets may be from different detectors, e.g., in a time-of-flight experiment, or from separate experiments, such as at several x-ray energies giving resonant information. The complementary use of x rays and neutrons is exemplified by a recent combined refinement of the monoclinic superstructure of magnetite, Fe3O4, below the 122 K Verwey transition, which reveals evidence for Fe(2+)/Fe(3+) charge ordering. Powder neutron diffraction data continue to be used for the solution and Rietveld refinement of magnetic structures. Time-of-flight instruments on cold neutron sources can produce data that have a high intensity and good resolution at high d-spacings. Such profiles have been used to study incommensurate magnetic structures such as FeAsO4 and beta-CrPO4. A multiphase, multidataset refinement of the phase separated perovskite (Pr0.35Y0.07Th0.04Ca0.04Sr0.5)MnO3 has been used to fit three components with different crystal and magnetic structures at low temperatures. PMID- 27366598 TI - X-Ray Spectrometry of Copper: New Results on an Old Subject. AB - We review recent, and some less recent, measurements of several emission spectra of copper. The results are discussed with special emphasis on elucidating the structure of the Kalpha 1,2 and Kbeta 1,3 diagram lines and their underlying transitions. These lines are found to contain ~30 % contribution from 3d spectator hole transitions. Other multielectronic transitions, the 2p spectator hole (satellites) and 1s spectator hole (hypersatellites) transitions were also measured. They are discussed paying special attention to the evolution of the lineshapes and intensities from the excitation threshold to saturation. Trends in the measured quantities depending on the spectator hole's shell and subshell are also discussed. PMID- 27366600 TI - Powder Diffraction: Least-Squares and Beyond. AB - This paper addresses some of the underlying statistical assumptions and issues in the collection and refinement of powder diffraction data. While standard data collection and Rietveld analysis have been extremely successful in providing structural information on a vast range of materials, there is often uncertainty about the true accuracy of the derived structural parameters. In this paper, we discuss a number of topics concerning data collection and the statistics of data analysis. We present a simple new function, the cumulative chi-squared distribution, for assessing regions of misfit in a diffraction pattern and introduce a matrix which relates the impact of individual points in a powder diffraction pattern with improvements in the estimated standard deviation of refined parameters. From an experimental viewpoint, we emphasise the importance of not over-counting at low-angles and the routine use of a variable counting scheme for data collection. Data analysis issues are discussed within the framework of maximum likelihood, which incorporates the current least-squares strategies but also enables the impact of systematic uncertainties in both observed and calculated data to be reduced. PMID- 27366601 TI - Direct Methods Optimised for Solving Crystal Structure by Powder Diffraction Data: Limits, Strategies, and Prospects. AB - The ab-initio crystal structure solution by powder diffraction data requires great efforts because of the collapse of the experimental information onto the one dimensional 2theta axis of the pattern. Different strategies will be described aiming at improving the process of extraction of the integrated intensities from the experimental pattern in order to make more straightforward the structure solution process by direct methods. Particular attention will be devoted to the EXPO program. Some of its performance will be analysed and results will be shown. PMID- 27366602 TI - The High Resolution Powder Diffraction Beam Line at ESRF. AB - The optical design and performance of the high-resolution powder diffraction beam line BM16 at ESRF are discussed and illustrated. Some recent studies carried out on BM16 are described, including crystal structure solution and refinement, anomalous scattering, in situ measurements, residual strain in engineering components, investigation of microstructure, and grazing-incidence diffraction from surface layers. The beam line is built on a bending magnet, and operates in the energy range from 5 keV to 40 keV. After the move to an undulator source in 2002, it will benefit from an extented energy range up to 60 keV and increased flux and resolution. It is anticipated that enhancements to the data quality will be achieved, leading to the solution of larger crystal structures, and improvements in the accuracy of refined structures. The systematic exploitation of anisotropic thermal expansion will help reduce the effects of peak overlap in the analysis of powder diffraction data. PMID- 27366603 TI - Global Rietveld Refinement. AB - Global optimisation methods of structure determination from powder diffraction data have risen to prominence in a relatively short space of time and they now constitute a key approach in the examination of polycrystalline molecular organic materials. A correctly formulated global optimisation approach may be regarded as a "global Rietveld refinement" that is capable of delivering accurate crystal structures from high-quality powder diffraction data. This paper focuses on how accuracy at all stages of a powder diffraction experiment impacts upon the overall structure solution process and particular attention is paid to assessing the degree of accuracy with which structures are returned from the global optimisation process. PMID- 27366604 TI - Bayesian Inference of Nanoparticle-Broadened X-Ray Line Profiles. AB - A single-step, self-contained method for determining the crystallite-size distribution and shape from experimental x-ray line profile data is presented. It is shown that the crystallite-size distribution can be determined without invoking a functional form for the size distribution, determining instead the size distribution with the least assumptions by applying the Bayesian/MaxEnt method. The Bayesian/MaxEnt method is tested using both simulated and experimental CeO2 data, the results comparing favourably with experimental CeO2 data from TEM measurements. PMID- 27366605 TI - The Remarkable Metrological History of Radiocarbon Dating [II]. AB - This article traces the metrological history of radiocarbon, from the initial breakthrough devised by Libby, to minor (evolutionary) and major (revolutionary) advances that have brought (14)C measurement from a crude, bulk [8 g carbon] dating tool, to a refined probe for dating tiny amounts of precious artifacts, and for "molecular dating" at the 10 ug to 100 ug level. The metrological advances led to opportunities and surprises, such as the non-monotonic dendrochronological calibration curve and the "bomb effect," that gave rise to new multidisciplinary areas of application, ranging from archaeology and anthropology to cosmic ray physics to oceanography to apportionment of anthropogenic pollutants to the reconstruction of environmental history. Beyond the specific topic of natural (14)C, it is hoped that this account may serve as a metaphor for young scientists, illustrating that just when a scientific discipline may appear to be approaching maturity, unanticipated metrological advances in their own chosen fields, and unanticipated anthropogenic or natural chemical events in the environment, can spawn new areas of research having exciting theoretical and practical implications. PMID- 27366606 TI - Characterization of Combinatorial Polymer Blend Composition Gradients by FTIR Microspectroscopy. AB - A new FTIR technique was developed for characterizing thin polymer films used in combinatorial materials science. Fourier transform infrared microspectroscopy mapping technique was used to determine the composition of polymer blend gradients. Composition gradients were made from poly(L-lactic acid) (PLLA) and poly(D,L-lactic acid) (PDLLA) in the form of thin films (6 cm * 2 cm) deposited on IR reflective substrates. Three composition gradient films were prepared and characterized. The results demonstrate the reproducibility and feasibility of a new, high-throughput approach for preparing and characterizing polymer composition gradients. The combination of composition gradient film technology and automated nondestructive FTIR microspectroscopy makes it possible to rapidly and quantitatively characterize polymer composition gradients for use in combinatorial materials science. PMID- 27366607 TI - Spot Weld Analysis With 2D Ultrasonic Arrays. AB - This paper describes a threefold method of testing the performance of an array based ultrasonic tool for nondestructive testing of spot welds. The tool is described in its capabilities, use, and advantages over existing counterparts. Performance testing for and the results from carrying out the testing are described. The three performance testing methods include 1) the use of calibrated samples, 2) comparisons with actual spot-welds, and 3) a performance evaluation of the embedded fitting software. The test of the fitting software was carried out by a comparison of results with reference fits supplied by the National Institute of Standards and Technology. PMID- 27366608 TI - Standard Reference Materials (SRMs) for the Calibration and Validation of Analytical Methods for PCBs (as Aroclor Mixtures). AB - Six Standard Reference Materials (SRMs(r)) have been prepared by the National Institute of Standards and Technology (NIST) for the determination of PCBs as different Aroclor mixtures in methanol. Six additional SRMs of the same Aroclors in transformer oil have also been prepared. Specifically, solutions of Aroclors 1016, 1232, 1242, 1254, and 1260 have been gravimetrically prepared (individually) in methanol and transformer oil, mixed, and transferred to amber glass ampoules in approximately 1.2 mL aliquots. Gas chromatography with electron capture detection (GC-ECD) has been used to verify the gravimetric data for each solution and transformer oil SRM. Liquid chromatography was used for the isolation of the Aroclors from the transformer oil SRMs prior to GC-ECD analysis. Separate calibration solutions and oils were prepared with Aroclor levels similar to those in each methanol solution and transformer oil SRM and were processed alongside the samples. The GC-ECD response of each Aroclor was monitored relative to internal standards that were added to the complex mixtures for quantification. The gravimetric concentrations of Aroclors 1242 and 1254 in methanol were also examined by the same method of analysis (GC-ECD) using several different sources of Aroclors and two different capillary GC columns: a 5 % phenyl methylpolysiloxane phase and a relatively non-polar phase. The preparation of the materials, the gas chromatographic results, and the certified concentration values for each Aroclor SRM are described in this paper. PMID- 27366609 TI - Simulation of Sheared Suspensions With a Parallel Implementation of QDPD. AB - A parallel quaternion-based dissipative particle dynamics (QDPD) program has been developed in Fortran to study the flow properties of complex fluids subject to shear. The parallelization allows for simulations of greater size and complexity and is accomplished with a parallel link-cell spatial (domain) decomposition using MPI. The technique has novel features arising from the DPD formalism, the use of rigid body inclusions spread across processors, and a sheared boundary condition. A detailed discussion of our implementation is presented, along with results on two distributed memory architectures. A parallel speedup of 24.19 was obtained for a benchmark calculation on 27 processors of a distributed memory cluster. PMID- 27366610 TI - Software Architecture for a Virtual Environment for Nano Scale Assembly (VENSA). AB - A Virtual Environment (VE) uses multiple computer-generated media to let a user experience situations that are temporally and spatially prohibiting. The information flow between the user and the VE is bidirectional and the user can influence the environment. The software development of a VE requires orchestrating multiple peripherals and computers in a synchronized way in real time. Although a multitude of useful software components for VEs exists, many of these are packaged within a complex framework and can not be used separately. In this paper, an architecture is presented which is designed to let multiple frameworks work together while being shielded from the application program. This architecture, which is called the Virtual Environment for Nano Scale Assembly (VENSA), has been constructed for interfacing with an optical tweezers instrument for nanotechnology development. However, this approach can be generalized for most virtual environments. Through the use of VENSA, the programmer can rely on existing solutions and concentrate more on the application software design. PMID- 27366611 TI - Intramural Comparison of NIST Laser and Optical Fiber Power Calibrations. AB - The responsivity of two optical detectors was determined by the method of direct substitution in four different NIST measurement facilities. The measurements were intended to demonstrate the determination of absolute responsivity as provided by NIST calibration services at laser and optical-communication wavelengths; nominally 633 nm, 850 nm, 1060 nm, 1310 nm, and 1550 nm. The optical detectors have been designated as checks standards for the purpose of routine intramural comparison of our calibration services and to meet requirements of the NIST quality system, based on ISO 17025. The check standards are two optical-trap detectors, one based on silicon and the other on indium gallium arsenide photodiodes. The four measurement services are based on: (1) the laser optimized cryogenic radiometer (LOCR) and free field collimated laser light; (2) the C series isoperibol calorimeter and free-field collimated laser light; (3) the electrically calibrated pyroelectric radiometer and fiber-coupled laser light; (4) the pyroelectric wedge trap detector, which measures light from a lamp source and monochromator. The results indicate that the responsivity of the check standards, as determined independently using the four services, agree to within the published expanded uncertainty ranging from approximately 0.02 % to 1.24 %. PMID- 27366612 TI - Erratum: Statistical Interpretation of Key Comparison Reference Value and Degrees of Equivalence. AB - [This corrects the article on p. 439 in vol. 108.]. PMID- 27366613 TI - Erratum: New National Air-Kerma-Strength Standards for (125)I and (103)Pd Brachytherapy Seeds. AB - [This corrects the article on p. 337 in vol. 108.]. PMID- 27366614 TI - Erratum: Determining the Magnetic Properties of 1 kg Mass Standards. AB - [This corrects the article on p. 209 in vol. 100.]. PMID- 27366615 TI - Uncertainty Propagation for NIST Visible Spectral Standards. AB - Uncertainties in the NIST spectral standards for detectors and sources in the visible wavelength range are propagated from the high accuracy cryogenic radiometer measurements, taking correlations into account at every stage. Partial correlations between spectral values at different wavelengths, important for subsequent radiometric calculations, are estimated. Uncertainty propagation through fitting and through transfer spectral measurements is described in detail. Detector uncertainties are propagated through the spectral comparator facility for external calibrations and for internal photometric quantities. Uncertainties in spectral irradiance are derived for the detector-based temperature determination, then propagated through working standards to calibrated artifacts. Spectral irradiance calibrations are generally provided at a limited number of wavelengths. Interpolation, rather than fitting, is recommended for the interpolation of NIST-provided spectral irradiance values. PMID- 27366616 TI - Uncertainties in Small-Angle Measurement Systems Used to Calibrate Angle Artifacts. AB - We have studied a number of effects that can give rise to errors in small-angle measurement systems when they are used to calibrate artifacts such as optical polygons. Of these sources of uncertainty, the most difficult to quantify are errors associated with the measurement of imperfect, non-flat faces of the artifact, causing the instrument to misinterpret the average orientation of the surface. In an attempt to shed some light on these errors, we have compared autocollimator measurements to angle measurements made with a Fizeau phase shifting interferometer. These two instruments have very different operating principles and implement different definitions of the orientation of a surface, but (surprisingly) we have not yet seen any clear differences between results obtained with the autocollimator and with the interferometer. The interferometer is in some respects an attractive alternative to an autocollimator for small angle measurement; it implements an unambiguous and robust definition of surface orientation in terms of the tilt of a best-fit plane, and it is easier to quantify likely errors of the interferometer measurements than to evaluate autocollimator uncertainty. PMID- 27366617 TI - Embedded MicroHeating Elements in Polymeric MicroChannels for Temperature Control and Fluid Flow Sensing. AB - This paper describes the first demonstration of temperature control and flow sensing of fluids using integrated circuit (IC)-based microheating elements embedded in microchannels molded in polydimethylsiloxane (PDMS). Fluid channels and connections to capillary tubing are molded in PDMS using a silicon wafer template. The PDMS film is then bonded to an IC that contains the micromachined microheating elements. Capillary tubes are inserted and fluids are externally pumped through the channels. Heating of the fluid is observed by the formation of bubbles on the microheating element. Sensing of fluid flow is demonstrated by measuring a change in the large signal resistance of the microheater analogous to a hot wire anemometer with a detection limit of +/- 320 pL/s. PMID- 27366618 TI - Uncertainty and Traceability for the CEESI Iowa Natural Gas Facility. AB - This paper analyzes the uncertainty of a secondary flow measurement facility that calibrates a significant fraction of United States and foreign flow meters used for custody transfer of natural gas. The facility, owned by the Colorado Experimental Engineering Station Incorporated (CEESI), is located in Iowa. This facility measures flow with nine turbine meter standards, each of which is traceable to the NIST primary flow standard. The flow capacity of this facility ranges from 0.7 actual m(3)/s to 10.7 actual m(3)/s at nominal pressures of 7174 kPa and at ambient temperatures. Over this flow range the relative expanded flow uncertainty varies from 0.28 % to 0.30 % (depending on flow). PMID- 27366619 TI - High-Resolution Observations of the Infrared Spectrum of Neutral Neon. AB - We have observed the spectrum of neutral neon (Ne I) emitted by a microwave excited electrodeless discharge lamp with the National Institute of Standards and Technology 2 m Fourier transform spectrometer. The spectra cover the regions 6929 A to 11 000 A with a resolution of 0.01 cm(-1) and 11 000 A to 47 589 A with a resolution of 0.007 cm(-1). We present a line list that includes more than 650 classified lines and provides an accurate and comprehensive description of the infrared spectrum. The response of the Fourier transform spectrometer was determined by using a radiometrically calibrated tungsten strip lamp, providing relative intensities that for moderate to strong lines are accurate to approximately 10 % over the entire range of the observations. The identities of many lines that were previously multiply classified are unambiguously resolved. PMID- 27366620 TI - Initial NIST AC QHR Measurements. AB - We demonstrate that dc quantized Hall resistance (dc QHR) guideline properties and dc and ac QHR values can be measured without changing sample probe lead connections at the QHR device, and report ac QHR values that converge to the dc QHR value when using four-terminal-pair ac QHR measurements. This was accomplished during one cooldown using single-series and quadruple-series connections outside the sample probe. The QHR was measured from 0 Hz to 5500 Hz in 1:1 ratio at 20 uA to +/-1 part in 10(7) uncertainties with a poor-quality QHR device. A good device would allow an order of magnitude smaller uncertainties over this frequency range. We exchanged positions of the QHR device and reference resistor in the bridge and remeasured the resistance ratios to remove dominant ac bridge effects. PMID- 27366621 TI - Frequency-Domain Models for Nonlinear Microwave Devices Based on Large-Signal Measurements. AB - In this paper, we introduce nonlinear large-signal scattering ( [Formula: see text]) parameters, a new type of frequency-domain mapping that relates incident and reflected signals. We present a general form of nonlinear large-signal [Formula: see text]-parameters and show that they reduce to classic [Formula: see text]-parameters in the absence of nonlinearities. Nonlinear large-signal impedance ( [Formula: see text]) and admittance ( [Formula: see text]) parameters are also introduced, and equations relating the different representations are derived. We illustrate how nonlinear large-signal [Formula: see text]-parameters can be used as a tool in the design process of a nonlinear circuit, specifically a single-diode 1 GHz frequency-doubler. For the case where a nonlinear model is not readily available, we developed a method of extracting nonlinear large-signal [Formula: see text]-parameters obtained with artificial neural network models trained with multiple measurements made by a nonlinear vector network analyzer equipped with two sources. Finally, nonlinear large-signal [Formula: see text] parameters are compared to another form of nonlinear mapping, known as nonlinear scattering functions. The nonlinear large-signal [Formula: see text]-parameters are shown to be more general. PMID- 27366622 TI - Nonlinearity Measurements of High-Power Laser Detectors at NIST. AB - We briefly explain the fundamentals of detector nonlinearity applicable to both electrical and optical nonlinearity measurements. We specifically discuss the attenuation method for optical nonlinearity measurement that the NIST system is based upon, and we review the possible sources of nonlinearity inherent to thermal detectors used with high-power lasers. We also describe, in detail, the NIST nonlinearity measurement system, in which detector responsivity can be measured at wavelengths of 1.06 um and 10.6 um, over a power range from 1 W to 1000 W. We present the data processing method used and show measurement results depicting both positive and negative nonlinear behavior. The expanded uncertainty of a typical NIST high-power laser detector calibration including nonlinearity characterization is about 1.3 %. PMID- 27366623 TI - Two Primary Standards for Low Flows of Gases. AB - We describe two primary standards for gas flow in the range from 0.1 to 1000 MUmol/s. (1 MUmol/s ? 1.3 cm(3)/min at 0 degrees C and 1 atmosphere.) The first standard is a volumetric technique in which measurements of pressure, volume, temperature, and time are recorded while gas flows in or out of a stainless steel bellows at constant pressure. The second standard is a gravimetric technique. A small aluminum pressure cylinder supplies gas to a laminar flow meter, and the integrated throughput of the laminar flow meter is compared to the weight decrease of the cylinder. The two standards, which have standard uncertainties of 0.019 %, agree to within combined uncertainties with each other and with a third primary standard at NIST based on pressure measurements at constant volume. PMID- 27366624 TI - Evaluation of Handheld Radionuclide Identifiers. AB - Characterization of commercially available instruments for measurement and identification of unknown radionuclides was carried out in support of the development and testing of the American National Standards Institute (ANSI) standard, N42.34, "Performance Criteria for Hand-held Instruments for the Detection and Identification of Radionuclides." Measurements were based on the performance of the devices, i.e., the capability of the detectors to ensure a correct radionuclide identification in a given time interval for various radioactive sources. PMID- 27366625 TI - Optical Diffraction in Close Proximity to Plane Apertures. III. Modified, Self Consistent Theory. AB - The classical theory of diffraction at plane apertures illuminated by normally incident light is modified so that diffraction on the source side of the screen is taken into consideration and the energy transport across the aperture plane is described by continuous functions. The modified field expressions involve the sums and differences of the Rayleigh-Sommerfeld diffraction integrals as descriptors of a bidirectional flow of energy in the near zones on either side of the aperture. The theory is valid for unpolarized fields, and a pragmatic argument is presented that it is applicable to metallic as well as black screens. The modified field expressions are used for numerical near-field computations of the diffraction profiles and transmission coefficients of circular apertures and slits. In the mid zone the modified theory is reduced to the Fresnel approximation, and here the latter may be used with confidence. PMID- 27366626 TI - Development of A High Throughput Method Incorporating Traditional Analytical Devices. AB - A high-throughput (high throughput is the ability to process large numbers of samples) and companion informatics system has been developed and implemented. High throughput is defined as the ability to autonomously evaluate large numbers of samples, while an informatics system provides the software control of the physical devices, in addition to the organization and storage of the generated electronic data. This high throughput system includes both an ultra-violet and visible light spectrometer (UV-Vis) and a Fourier transform infrared spectrometer (FTIR) integrated with a multi sample positioning table. This method is designed to quantify changes in polymeric materials occurring from controlled temperature, humidity and high flux UV exposures. The integration of the software control of these analytical instruments within a single computer system is presented. Challenges in enhancing the system to include additional analytical devices are discussed. PMID- 27366627 TI - Determining the Uncertainty of X-Ray Absorption Measurements. AB - X-ray absorption (or more properly, x-ray attenuation) techniques have been applied to study the moisture movement in and moisture content of materials like cement paste, mortar, and wood. An increase in the number of x-ray counts with time at a location in a specimen may indicate a decrease in moisture content. The uncertainty of measurements from an x-ray absorption system, which must be known to properly interpret the data, is often assumed to be the square root of the number of counts, as in a Poisson process. No detailed studies have heretofore been conducted to determine the uncertainty of x-ray absorption measurements or the effect of averaging data on the uncertainty. In this study, the Poisson estimate was found to adequately approximate normalized root mean square errors (a measure of uncertainty) of counts for point measurements and profile measurements of water specimens. The Poisson estimate, however, was not reliable in approximating the magnitude of the uncertainty when averaging data from paste and mortar specimens. Changes in uncertainty from differing averaging procedures were well-approximated by a Poisson process. The normalized root mean square errors decreased when the x-ray source intensity, integration time, collimator size, and number of scanning repetitions increased. Uncertainties in mean paste and mortar count profiles were kept below 2 % by averaging vertical profiles at horizontal spacings of 1 mm or larger with counts per point above 4000. Maximum normalized root mean square errors did not exceed 10 % in any of the tests conducted. PMID- 27366628 TI - Analytical Representations of Elastic Moduli Data With Simultaneous Dependence on Temperature and Porosity. AB - An analytical model providing simultaneous, self-consistent representations of the temperature and porosity dependence of the elastic and bulk moduli of polycrystalline ceramics is applied to data compiled from the literature for 24 oxide ceramics. PMID- 27366629 TI - Electron-Impact Cross Sections for Ground State to np Excitations of Sodium and Potassium. AB - Cross sections for electron impact excitation of atoms are important for modeling of low temperature plasmas and gases. While there are many experimental and theoretical results for excitation to the first excited states, little information is available for excitation to higher states. We present here calculations of excitations from the ground state to the np levels of sodium (n = 3 through 11) and potassium (n = 4 through 12). We also present a calculation for a transition from the excited sodium level 3p to 3d to show the generality of the method. Scaling formulas developed earlier by Kim [Phys. Rev. A 64, 032713 (2001)] for plane-wave Born cross sections are used. These formulas have been shown to be remarkably accurate yet simple to use. We have used a core polarization potential in a Dirac-Fock wave function code to calculate target atom wave functions and a matching form of the dipole transition operator to calculate oscillator strengths and Born cross sections. The scaled Born results here for excitation to the first excited levels are in very good agreement with experimental and other theoretical data, and the results for excitation to the next few levels are in satisfactory agreement with the limited data available. The present results for excitation to the higher levels are believed to be the only data available. PMID- 27366630 TI - Stability Comparison of Recordable Optical Discs-A Study of Error Rates in Harsh Conditions. AB - The reliability and longevity of any storage medium is a key issue for archivists and preservationists as well as for the creators of important information. This is particularly true in the case of digital media such as DVD and CD where a sufficient number of errors may render the disc unreadable. This paper describes an initial stability study of commercially available recordable DVD and CD media using accelerated aging tests under conditions of increased temperature and humidity. The effect of prolonged exposure to direct light is also investigated and shown to have an effect on the error rates of the media. Initial results show that high quality optical media have very stable characteristics and may be suitable for long-term storage applications. However, results also indicate that significant differences exist in the stability of recordable optical media from different manufacturers. PMID- 27366631 TI - A Small-Volume Apparatus for the Measurement of Phase Equilibria. AB - An apparatus has been designed and constructed for the measurement of vapor liquid equilibrium properties. The main components of the apparatus consist of an equilibrium cell and a vapor circulation pump. The cell and all of the system valves are housed inside a temperature controlled, insulated aluminum block. The temperature range of the apparatus is 260 K to 380 K to pressures of 6 MPa. The uncertainty of the temperature measurement is 0.03 K, and the uncertainty in the pressure measurement is 9.8 * 10(-4) MPa. An automated data acquisition system is used to measure temperature and pressure at equilibrium. The apparatus has been performance tested by measuring the vapor pressures of propane, butane, and a standard mixture of propane + butane. PMID- 27366632 TI - SRM 2460/2461 Standard Bullets and Casings Project. AB - The National Institute of Standards and Technology Standard Reference Material (SRM) 2460/2461 standard bullets and casings project will provide support to firearms examiners and to the National Integrated Ballistics Information Network (NIBIN) in the United States. The SRM bullet is designed as both a virtual and a physical bullet profile signature standard. The virtual standard is a set of six digitized bullet profile signatures originally traced from six master bullets fired at the Bureau of Alcohol, Tobacco and Firearms (ATF) and the Federal Bureau of Investigation (FBI). By using the virtual signature standard to control the tool path on a numerically controlled diamond turning machine, 40 SRM bullets were produced. A profile signature measurement system was established for the SRM bullets. The profile signature differences are quantified by the maximum of the cross correlation function and by the signature difference between pairs of compared profile signatures measured on different SRM bullets. Initial measurement results showed high reproducibility for both the measurement system and production process of the SRM bullets. A traceability scheme has been proposed to establish the measurement traceability for nationwide bullet signature measurements to NIST, ATF and FBI. Prototype SRM casings have also been developed. PMID- 27366633 TI - Properties of Nanostructured Hydroxyapatite Prepared by a Spray Drying Technique. AB - In previous studies nano sized hydroxyapatite (HA) particles were prepared by solgel or precipitation methods, in which the products were washed by aqueous or non-aqueous liquids to remove impurities or undesired components. The washing is know to modify the surfaces of the cystalline particles. This study evaluated properties of nano HA materials prepared by a spray drying method in which the HA product was not exposed to any liquid after its formation. The spray drying apparatus consisted of a nozzle that sprayed an acidic calcium phosphate solution in the form of a fine mist into a stream of filtered air flowing through a heated glass column. The water and volatile acid were evaporated by the time the mist reached the end of the column, and the fine particles were collected by an electrostatic precipitator. Powder x ray diffraction patterns suggested the material was amorphous, exhibiting a single broad peak at 30.5 degrees 2theta. However, high resolution transmission electron microscopic analysis showed that the particles, some of which were 5 nm in size, exhibited well ordered HA lattice fringes. Small area diffraction patterns were indicative of HA. Fourier transfer infrared spectroscopy showed patterns of typical of HA with small amounts of HPO4 (2-). The thermodynamic solubility product of the nano HA was 3.3 * 10(-94) compared to 1 * 10(-117) for macro scale crystalline HA. These results showed that a spray drying technique can be used to prepare nanometer sized crystalline HA that have significantly different physicochemical properties than those of its bulk-scale counterpart. PMID- 27366634 TI - Preparation and Comprehensive Characterization of a Calcium Hydroxyapatite Reference Material. AB - Numerous biological and chemical studies involve the use of calcium hydroxyapatite (HA), Ca10(PO4)6(OH)2. In this study detailed physicochemical characterization of HA, prepared from an aqueous solution, was carried out employing different methods and techniques: chemical and thermal analyses, x-ray diffraction, infrared and Raman spectroscopies, scanning and transmission microscopies, and Brunauer, Emmett, and Teller (BET) surface-area method. The contents of calcium (Ca(2+)), phosphate (PO4 (3-)), hydroxide (OH(-)), hydrogenphosphate (HPO4 (2-)), water (H2O), carbonate (CO3 (2-)), and trace constituents, the Ca/P molar ratio, crystal size and morphology, surface area, unit-cell parameters, crystallinity, and solubility of this HA were determined. This highly pure, homogeneous, and highly crystalline HA is certified as a National Institute of Standards and Technology (NIST) standard reference material, SRM 2910. PMID- 27366635 TI - Ambiguities in Powder Indexing: Conjunction of a Ternary and Binary Lattice Metric Singularity in the Cubic System. AB - A lattice metric singularity occurs when unit cells defining two (or more) lattices yield the identical set of unique calculated d-spacings. The existence of such singularities, therefore, has a practical and theoretical impact on the indexing of powder patterns. For example, in experimental practice an indexing program may find only the lower symmetry member of a singularity. Obviously, it is important to recognize such cases and know how to proceed. Recently, we described: a binary singularity involving a monoclinic and a rhombohedral lattice in a subcell-supercell relationship anda second type of singularity-a ternary singularity-in which two of the three lattices are in a derivative composite relationship. In this work, we describe a ternary lattice metric singularity involving a cubic P, a tetragonal P, and an orthorhombic C lattice. Furthermore, there is a binary singularity, involving a hexagonal P and orthorhombic P lattice, which is characterized by a set of unique d-spacings very close to that of the ternary singularity. The existence of such singularities is more common than once thought and requires a paradigm shift in experimental practice. In addition singularities provide opportunities in material design as they point to highly specialized lattices that may be associated with unusual physical properties. PMID- 27366636 TI - Potential ecosystem service delivery by endemic plants in New Zealand vineyards: successes and prospects. AB - Vineyards worldwide occupy over 7 million hectares and are typically virtual monocultures, with high and costly inputs of water and agro-chemicals. Understanding and enhancing ecosystem services can reduce inputs and their costs and help satisfy market demands for evidence of more sustainable practices. In this New Zealand work, low-growing, endemic plant species were evaluated for their potential benefits as Service Providing Units (SPUs) or Ecosystem Service Providers (ESPs). The services provided were weed suppression, conservation of beneficial invertebrates, soil moisture retention and microbial activity. The potential Ecosystem Dis-services (EDS) from the selected plant species by hosting the larvae of a key vine moth pest, the light-brown apple moth (Epiphyas postvittana), was also quantified. Questionnaires were used to evaluate winegrowers' perceptions of the value of and problems associated with such endemic plant species in their vineyards. Growth and survival rates of the 14 plant species, in eight families, were evaluated, with Leptinella dioica (Asteraceae) and Acaena inermis 'purpurea' (Rosaceae) having the highest growth rates in terms of area covered and the highest survival rate after 12 months. All 14 plant species suppressed weeds, with Leptinella squalida, Geranium sessiliforum (Geraniaceae), Hebe chathamica (Plantaginaceae), Scleranthus uniflorus (Caryophyllaceae) and L. dioica, each reducing weed cover by >95%. Plant species also differed in the diversity of arthropods that they supported, with the Shannon Wiener diversity index (H') for these taxa ranging from 0 to 1.3. G. sessiliforum and Muehlenbeckia axillaris (Polygonaceae) had the highest invertebrate diversity. Density of spiders was correlated with arthropod diversity and G. sessiliflorum and H. chathamica had the highest densities of these arthropods. Several plant species associated with higher soil moisture content than in control plots. The best performing species in this context were A. inermis 'purpurea' and Lobelia angulata (Lobeliaceae). Soil beneath all plant species had a higher microbial activity than in control plots, with L. dioica being highest in this respect. Survival proportion to the adult stage of the moth pest, E. postvittana, on all plant species was poor (<0.3). When judged by a ranking combining multiple criteria, the most promising plant species were (in decreasing order) G. sessiliflorum, A. inermis 'purpurea', H. chathamica, M. axillaris, L. dioica, L. angulata, L. squalida and S. uniflorus. Winegrowers surveyed said that they probably would deploy endemic plants around their vines. This research demonstrates that enhancing plant diversity in vineyards can deliver SPUs, harbour ESPs and therefore deliver ES. The data also shows that growers are willing to follow these protocols, with appropriate advice founded on sound research. PMID- 27366637 TI - Genetic markers of inflammation may not contribute to metabolic traits in Mexican children. AB - BACKGROUND: Low-grade chronic inflammation is a common feature of obesity and its cardio-metabolic complications. However, little is known about a possible causal role of inflammation in metabolic disorders. Mexico is among the countries with the highest obesity rates in the world and the admixed Mexican population is a relevant sample due to high levels of genetic diversity. METHODS: Here, we studied 1,462 Mexican children recruited from Mexico City. Six genetic variants in five inflammation-related genes were genotyped: rs1137101 (leptin receptor (LEPR)), rs7305618 (hepatocyte nuclear factor 1 alpha (HNF1A)), rs1800629 (tumor necrosis factor alpha (TNFA)), rs1800896, rs1800871 (interleukin-10 (IL-10)), rs1862513 (resistin (RETN)). Ten continuous and eight binary traits were assessed. Linear and logistic regression models were used adjusting for age, sex, and recruitment centre. RESULTS: We found that one SNP displayed a nominal evidence of association with a continuous trait: rs1800871 (IL-10) with LDL (beta = -0.068 +/- 1.006, P = 0.01). Subsequently, we found one nominal association with a binary trait: rs7305618 (HNF1A) with family history of hypertension (odds ratio = 1.389 [1.054-1.829], P = 0.02). However, no P-value passed the Bonferroni correction for multiple testing. DISCUSSION: Our data in a Mexican children population are consistent with previous reports in European adults in failing to demonstrate an association between inflammation-associated single nucleotide polymorphisms (SNPs) and metabolic traits. PMID- 27366638 TI - An exploratory pilot study of mechanisms of action within normative feedback for adult drinkers. AB - Background. Normative feedback (NF), or receiving information about one's drinking compared to peer drinking norms, is one of the most widely used brief interventions for prevention and intervention for hazardous alcohol use. NF has demonstrated predominantly small but significant effect sizes for intention to change and other drinking related outcomes. Identifying mechanisms of action may improve the effectiveness of NF; however, few studies have examined NF's mechanisms of action, particularly among adults. Objective. This study is an exploratory analysis of two theorized mechanisms of NF: discrepancy (specifically personal dissonance-the affective response to feedback) and belief in the accuracy of feedback. Method. Using Amazon's Mechanical Turk, 87 men (n = 56) and women (n = 31) completed an online survey during which they were asked about their perceptions about their drinking and actual drinking behaviors. Then participants were provided tailored NF and evaluated for their reactions. Severity of discrepancy was measured by the difference between one's estimated percentile ranking of drinking compared to peers and actual percentile ranking. Surprise and worry reported due to the discrepancy were proxies for personal dissonance. Participants were also asked if they believed the feedback and if they had any plans to change their drinking. Mediation analyses were implemented, exploring whether surprise, worry, or belief in the accuracy of feedback mediated severity of discrepancy's impact on plan for change. Results. Among this sample of adult drinkers, severity of discrepancy did not predict plan for change, and personal dissonance did not mediate severity of discrepancy. Severity of discrepancy was mediated by belief in the accuracy of feedback. In addition, viewing one's drinking as a problem prior to feedback and post-NF worry both predicted plan for change independently. Conclusions. Results revealed that NF may not work to create personal dissonance through discrepancy, but belief in the accuracy of feedback may be important. It appears the more one believes the feedback, the more one makes a plan for change, suggesting practitioners should be mindful of how information within feedback is presented. Findings also indicate NF may work by validating a preexisting perception that drinking is a problem instead of creating concern related to discrepancy where none existed. Limitations regarding generalizability are discussed. PMID- 27366639 TI - Adaptive changes in chlorophyll content and photosynthetic features to low light in Physocarpus amurensis Maxim and Physocarpus opulifolius "Diabolo". AB - The present study aims to investigate the differences in leaf pigment content and the photosynthetic characteristics under natural and low light intensities between the Chinese native Physocarpus amurensis Maxim and the imported Physocarpus opulifolius "Diabolo" from North America. We aim to discuss the responses and the adaptive mechanism of these two cultivars of Physocarpus to a low light environment. The results show that the specific leaf area (SLA) and the chlorophyll content were significantly increased in the leaves of both Physocarpus cultivars in response to a low light intensity, and the SLA and chlorophyll content were higher in the leaves of low light-treated P. opulifolius "Diabolo" compared with the leaves of low light-treated P. amurensis Maxim. Moreover, the content of anthocyanin was markedly reduced in the leaves of P. opulifolius "Diabolo" under low light intensity, which allowed for a greater capacity of photon capture under the low light condition. Under natural light, the photosynthetic carbon assimilation capacity was greater in the leaves of P. amurensis Maxim compared with the leaves of P. opulifolius "Diabolo" that were rich with anthocyanin. However, in response to low light, AQY, P max, LCP and LSP decreased to a lesser extent in the leaves of P. opulifolius "Diabolo" compared with the leaves of P. amurensis Maxim. These results suggest that P. opulifolius "Diabolo" exhibits a greater ability in adaption to low light, and it is probably related to the relatively higher chlorophyll content and the smaller SLA in the leaves of P. opulifolius "Diabolo." In addition, the low light intensity resulted in a reduced photochemical activity of photosystem (PS) II in the leaves of both Physocarpus, as evidenced by increased values of the relative variable fluorescence at point J and point I on the OJIP curve. This result suggests that the electron acceptor in PS II was the major responsive site to the low light stress in the leaves of both Physocarpus cultivars, and that the low light intensity significantly inhibited electron transfer on the acceptor side of PS II and reduced the activity of the oxygen-evolving complex (OEC) in the leaves of both Physocarpus cultivars. The PS II function in P. opulifolius "Diabolo" was higher than that in P. amurensis Maxim in response to low light. Under low light, the composition of photosynthetic pigments was altered in the leaves of P. opulifolius "Diabolo" in order to maintain a relatively high activity of primary photochemical reactions, and this is the basis of the greater photosynthetic carbon assimilation capacity and one of the main reasons for the better shade tolerance in P. opulifolius "Diabolo." PMID- 27366640 TI - The in vitro and in vivo effects of constitutive light expression on a bioluminescent strain of the mouse enteropathogen Citrobacter rodentium. AB - Bioluminescent reporter genes, such as those from fireflies and bacteria, let researchers use light production as a non-invasive and non-destructive surrogate measure of microbial numbers in a wide variety of environments. As bioluminescence needs microbial metabolites, tagging microorganisms with luciferases means only live metabolically active cells are detected. Despite the wide use of bioluminescent reporter genes, very little is known about the impact of continuous (also called constitutive) light expression on tagged bacteria. We have previously made a bioluminescent strain of Citrobacter rodentium, a bacterium which infects laboratory mice in a similar way to how enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC) infect humans. In this study, we compared the growth of the bioluminescent C. rodentium strain ICC180 with its non-bioluminescent parent (strain ICC169) in a wide variety of environments. To understand more about the metabolic burden of expressing light, we also compared the growth profiles of the two strains under approximately 2,000 different conditions. We found that constitutive light expression in ICC180 was near-neutral in almost every non-toxic environment tested. However, we also found that the non-bioluminescent parent strain has a competitive advantage over ICC180 during infection of adult mice, although this was not enough for ICC180 to be completely outcompeted. In conclusion, our data suggest that constitutive light expression is not metabolically costly to C. rodentium and supports the view that bioluminescent versions of microbes can be used as a substitute for their non bioluminescent parents to study bacterial behaviour in a wide variety of environments. PMID- 27366641 TI - The impact of feature selection on one and two-class classification performance for plant microRNAs. AB - MicroRNAs (miRNAs) are short nucleotide sequences that form a typical hairpin structure which is recognized by a complex enzyme machinery. It ultimately leads to the incorporation of 18-24 nt long mature miRNAs into RISC where they act as recognition keys to aid in regulation of target mRNAs. It is involved to determine miRNAs experimentally and, therefore, machine learning is used to complement such endeavors. The success of machine learning mostly depends on proper input data and appropriate features for parameterization of the data. Although, in general, two-class classification (TCC) is used in the field; because negative examples are hard to come by, one-class classification (OCC) has been tried for pre-miRNA detection. Since both positive and negative examples are currently somewhat limited, feature selection can prove to be vital for furthering the field of pre-miRNA detection. In this study, we compare the performance of OCC and TCC using eight feature selection methods and seven different plant species providing positive pre-miRNA examples. Feature selection was very successful for OCC where the best feature selection method achieved an average accuracy of 95.6%, thereby being ~29% better than the worst method which achieved 66.9% accuracy. While the performance is comparable to TCC, which performs up to 3% better than OCC, TCC is much less affected by feature selection and its largest performance gap is ~13% which only occurs for two of the feature selection methodologies. We conclude that feature selection is crucially important for OCC and that it can perform on par with TCC given the proper set of features. PMID- 27366642 TI - Simple approach for ranking structure determining residues. AB - Mutating residues has been a common task in order to study structural properties of the protein of interest. Here, we propose and validate a simple method that allows the identification of structural determinants; i.e., residues essential for preservation of the stability of global structure, regardless of the protein topology. This method evaluates all of the residues in a 3D structure of a given globular protein by ranking them according to their connectivity and movement restrictions without topology constraints. Our results matched up with sequence based predictors that look up for intrinsically disordered segments, suggesting that protein disorder can also be described with the proposed methodology. PMID- 27366643 TI - Biodiversity management of organic orchard enhances both ecological and economic profitability. AB - Organic farming has been regarded as an alternative solution for both agricultural sustainability and human health maintenance. Few researches have concentrated on the differences of biodiversity and eco-economic benefits between organic and conventional orchards. Organic management (OM) of orchards mainly includes taking advantage of natural enemies and beneficial weeds as well as soil organisms and controlling harmful pests. Here we conducted a three-year experiment on the effects of managing biodiversity in an organic apple orchard, using cattle manure to enrich soil biota, propagating native plant to suppress weeds and applying ecological pest management to control pests. The effect was assessed against the conventional management (CM) model. We found that OM enhanced soil organic carbon, total nitrogen, microbial biomass carbon and nitrogen. The 16S rDNA high-throughput sequencing results indicated that the dominant bacterial phyla of the top soil were Proteobacteria and Actinobacteria, and OM had richer bacteria diversity with a 7% higher Shannon's index than the CM. In particular, the relative abundance of rhizobium in the OM was higher than that of the CM. For OM, Duchesnea indica was an ideal ground-cover plant to control weeds through winning the niche competition and thus decreased weeds' Simpson, Shannon-Wiener and Pielou index by 38.2%, 53.8% and 16.9% separately. The phototactic pests' weight and scarab beetle's population were effectively decreased by 35% and 86% respectively through long time control and prevention. OM had an average of 20 times more earthworms than CM, and the maximum density had reached 369 m(-2) (0-20 cm soil). The dominant earthworm species of the OM were detritivores which preferring soil with high organic matter content. Due to no synthetic chemicals being used, the OM produced much safer apple fruits which were sold at high prices. Economically, up to a 103% increase of output-input ratio had been achieved in the OM. Our study clearly demonstrated that biodiversity management without chemical pollution increased the biodiversity of beneficial organisms, reduced antagonists of the fruit tree, and enhanced economic benefits of the apple orchard. PMID- 27366644 TI - The impact of an invasive ambrosia beetle on the riparian habitats of the Tijuana River Valley, California. AB - The Tijuana River Valley is the first natural habitat in California to be substantially invaded by the Kuroshio Shot Hole Borer (KSHB, Euwallacea sp.), an ambrosia beetle native to Southeast Asia. This paper documents the distribution of the KSHB in the riparian vegetation in the valley and assesses the damage done to the vegetation as of early 2016, approximately six months after the beetle was first observed in the valley. I divided the riparian habitats into 29 survey units so that the vegetation within each unit was relatively homogenous in terms of plant species composition, age and density. From a random point within each unit, I examined approximately 60 individuals of the dominant plant species for evidence of KSHB infestation and evidence of major damage such as limb breakage. In the 22 forested units,I examined the dominant arroyo and black willows (Salix lasiolepis Benth. and S. gooddingii C.R. Ball), and in the seven scrub units, I examined mule fat (Baccharis salicifolia (Ruiz & Pav.) Pers.). Evidence of KSHB infestation was found in 25 of the 29 units. In the forest units, infestation rates ranged from 0 to 100% and were high (>60%) in 16 of the units. In the scrub units, infestation rates ranged from 0 to 33%. Infestation rates were significantly correlated with the wetness of a unit; wetter units had higher infestation rates. Evidence of major physical damage was found in 24 units, and dense stands of willows were reduced to broken trunks in several areas. Overall, I estimated that more than 280,000 (70%) of the willows in the valley were infested, and more than 140,000 had suffered major limb damage. In addition, I recorded evidence of KSHB infestation in the other common plant species in the valley; of the 23 species examined, 14 showed evidence of beetle attack. The four species with the highest rates of infestation were native trees in the Salicaceae family. The three species considered to be the worst invasive plants in the valley, Ricinus communis L., Tamarix ramosissima Ledeb. and Arundo donax L., had low rates of infestation. Several findings from this study have significance for resource managers: (1) the KSHB attack caused extensive mortality of trees soon after being first discovered so, if managers are to control the spread of the beetle, they will need to develop an effective early detection and rapid response program; (2) infestation rates were highest in units that were wet, so resource managers trying to detect the beetle in other areas should thoroughly search trees near water, particularly nutrient-enriched water; (3) the infestation appears to be a novel form of disturbance, and the affected forests may need special management actions in order to recover; and (4) the infestation has altered the structure of the forest canopy, and this is likely to promote the growth of invasive plant species that were relatively inconspicuous in the forests prior to the beetle attack but will now need more attention. PMID- 27366645 TI - Diversity of Fusarium species isolated from UK forage maize and the population structure of F. graminearum from maize and wheat. AB - Pre-harvest contamination of forage maize by mycotoxin producing Fusarium species was investigated in the UK in 2011 and 2012. A total of 15 Fusarium species were identified from a collection of 1,761 Fusarium isolates recovered from maize stalks and kernels. This study characterized the diversity of Fusarium species present in forage maize in the UK. The predominant species detected were F. graminearum (32.9%) and F. culmorum (34.1%). Along with those species; F. avenacem, F. cerealis, F. equiseti, F. langsethiae, F. napiforme, F. oxysporum, F. poae, F. proliferatum, F. scripi, F. solani, F. subglutinans, F. tricinctum and, F. verticillioides were occasionally isolated. The trichothecene genotypes for F. graminearum were determined to be 84.9% deoxynivalenol (DON) and 15.0% nivalenol (NIV) while F. culmorum isolates were determined to have 24.9% DON and 75.1% NIV genotypes. A Bayesian model-based clustering method with nine variable number of tandem repeat markers was used to evaluate the population genetic structure of 277 F. graminearum isolates from the maize and wheat in the UK. There were three genetic clusters detected which were DON in maize, NIV in maize and DON in wheat. There were high admixture probabilities for 14.1% of the isolates in the populations. In conclusion, increased maize production in the UK and the high admixture rates in a significant portion of F. graminearum populations in maize and wheat will contribute to a new pathogen population which will further complicate breeding strategies for tolerance or resistance to this pathogen in both crops. PMID- 27366646 TI - Clinical and prognostic value of preoperative hydronephrosis in upper tract urothelial carcinoma: a systematic review and meta-analysis. AB - Background. Epidemiological studies have reported various results relating preoperative hydronephrosis to upper tract urothelial carcinoma (UTUC). However, the clinical significance and prognostic value of preoperative hydronephrosis in UTUC remains controversial. The aim of this study was to provide a comprehensive meta-analysis of the extent of the possible association between preoperative hydronephrosis and the risk of UTUC. Methods. We searched PubMed, ISI Web of Knowledge, and Embase to identify eligible studies written in English. Summary odds ratios (ORs) or hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models. Results. Nineteen relevant studies, which had a total of 5,782 UTUC patients enrolled, were selected for statistical analysis. The clinicopathological and prognostic relevance of preoperative hydronephrosis was evaluated in the UTUC patients. The results showed that all tumor stages, lymph node status and tumor location, as well as the risk of cancer-specific survival (CSS), overall survival (OS), recurrence-free survival (RFS) and metastasis-free survival (MFS) were significantly different between UTUC patients with elevated preoperative hydronephrosis and those with low preoperative hydronephrosis. High preoperative hydronephrosis indicated a poor prognosis. Additionally, significant correlations between preoperative hydronephrosis and tumor grade (high grade vs. low grade) were observed in UTUC patients; however, no significant difference was observed for tumor grading (G1 vs. G2 + G3 and G1 + G2 vs. G3). In contrast, no such correlations were evident for recurrence status or gender in UTUC patients. Conclusions. The results of this meta-analysis suggest that preoperative hydronephrosis is associated with increased risk and poor survival in UTUC patients. The presence of preoperative hydronephrosis plays an important role in the carcinogenesis and prognosis of UTUC. PMID- 27366647 TI - Interrater reliability of quantitative ultrasound using force feedback among examiners with varied levels of experience. AB - Background. Quantitative ultrasound measures are influenced by multiple external factors including examiner scanning force. Force feedback may foster the acquisition of reliable morphometry measures under a variety of scanning conditions. The purpose of this study was to determine the reliability of force feedback image acquisition and morphometry over a range of examiner-generated forces using a muscle tissue-mimicking ultrasound phantom. Methods. Sixty material thickness measures were acquired from a muscle tissue mimicking phantom using B-mode ultrasound scanning by six examiners with varied experience levels (i.e., experienced, intermediate, and novice). Estimates of interrater reliability and measurement error with force feedback scanning were determined for the examiners. In addition, criterion-based reliability was determined using material deformation values across a range of examiner scanning forces (1-10 Newtons) via automated and manually acquired image capture methods using force feedback. Results. All examiners demonstrated acceptable interrater reliability (intraclass correlation coefficient, ICC = .98, p < .001) for material thickness measures obtained using force feedback. Individual examiners exhibited acceptable reliability with the criterion-based reference measures (ICC > .90, p < .001), independent of their level of experience. The measurement error among all examiners was 1.5%-2.9% across all applied stress conditions. Conclusion. Manual image capture with force feedback may aid the reliability of morphometry measures across a range of examiner scanning forces, and allow for consistent performance among examiners with differing levels of experience. PMID- 27366648 TI - In vitro evaluation of antifungal activity of monolaurin against Candida albicans biofilms. AB - Monolaurin (also known as glycerol monolaurate) is a natural compound found in coconut oil and is known for its protective biological activities as an antimicrobial agent. The nature of oral candidiasis and the increased antifungal resistance demand the search for novel antifungal therapeutic agents. In this study, we examine the antifungal activity of monolaurin against Candida albicans biofilms (strain ATCC:SC5314/MYA2876) in vitro and investigate whether monolaurin can alter gene expression of host inflammatory cytokines, IL-1alpha and IL-1beta. In a co-culture model, oral fibroblast cells were cultured simultaneously with C. albicans for 24 hrs followed by the exposure to treatments of monolaurin (3.9 2,500 uM), positive control fluconazole (32.2 uM), and vehicle control group (1% ethanol), which was a model used to evaluate the cytotoxicity of monolaurin on fibroblasts as well as to analyze morphological characteristics of biofilms through fluorescence microscopy. In addition, the co-culture model was used for RNA extraction of oral fibroblasts to assess gene expression of host inflammatory cytokines, using quantitative real-time PCR. Our results showed the MIC and MFC of monolaurin were in the range 62.5-125 uM and 125-250 uM, respectively. Biofilm antifungal assay showed significant reduction in Log (CFU/ml) of biofilms treated with 1,250 and 2,500 uM of 1-monolaurin when compared to the control groups . There was also a significant down-regulation of IL-1alpha and IL-1beta in the co culture treated with monolaurin. It can be concluded that monolaurin has a potential antifungal activity against C. albicans and can modulate the pro inflammatory response of the host. PMID- 27366649 TI - First records of Canis dirus and Smilodon fatalis from the late Pleistocene Tule Springs local fauna, upper Las Vegas Wash, Nevada. AB - Late Pleistocene groundwater discharge deposits (paleowetlands) in the upper Las Vegas Wash north of Las Vegas, Nevada, have yielded an abundant and diverse vertebrate fossil assemblage, the Tule Springs local fauna (TSLF). The TSLF is the largest open-site vertebrate fossil assemblage dating to the Rancholabrean North American Land Mammal Age in the southern Great Basin and Mojave Desert. Over 600 discrete body fossil localities have been recorded from the wash, including an area that now encompasses Tule Springs Fossil Beds National Monument (TUSK). Paleowetland sediments exposed in TUSK named the Las Vegas Formation span the last 250 ka, with fossiliferous sediments spanning ~100-13 ka. The recovered fauna is dominated by remains of Camelopsand Mammuthus, and also includes relatively common remains of extinct Equusand Bisonas well as abundant vertebrate microfaunal fossils. Large carnivorans are rare, with only Puma concolor and Panthera atrox documented previously. Postcranial remains assigned to the species Canis dirus (dire wolf) and Smilodon fatalis (sabre-toothed cat) represent the first confirmed records of these species from the TSLF, as well as the first documentation of Canis dirus in Nevada and the only known occurrence of Smilodonin southern Nevada. The size of the recovered canid fossil precludes assignment to other Pleistocene species of Canis. The morphology of the felid elements differentiates them from other large predators such as Panthera, Homotherium, and Xenosmilus, and the size of the fossils prevents assignment to other species of Smilodon. The confirmed presence of S. fatalis in the TSLF is of particular interest, indicating that this species inhabited open habitats. In turn, this suggests that the presumed preference of S. fatalis for closed-habitat environments hunting requires further elucidation. PMID- 27366650 TI - Towards evenly distributed grazing patterns: including social context in sheep management strategies. AB - Background. A large proportion of natural grasslands around the world is exposed to overgrazing resulting in land degradation and biodiversity loss. Although there is an increasing effort in the promotion of sustainable livestock management, rangeland degradation still occurs because animals' foraging behaviour is highly selective at different spatial scales. The assessment of the ecological mechanisms modulating the spatial distribution of grazing and how to control it has critical implications for long term conservation of resources and the sustainability of livestock production. Considering the relevance of social interactions on animals' space use patterns, our aim was to explore the potential effects of including animals' social context into management strategies using domestic sheep grazing in rangelands as case study. Methods. We used GPS data from 19 Merino sheep (approximately 10% of the flock) grazing on three different paddocks (with sizes from 80 to 1000 Ha) during a year, to estimate resource selection functions of sheep grazing in flocks of different levels of heterogeneity. We assessed the effects of sheep class (i.e., ewes, wethers, and hoggets), age, body condition and time since release on habitat selection patterns. Results. We found that social rank was reflected on sheep habitat use, where dominant individuals (i.e., reproductive females) used more intensively the most preferred areas and low-ranked (i.e., yearlings) used less preferred areas. Our results showed that when sheep grazed on more heterogeneous flocks, grazing patterns were more evenly distributed at all the paddocks considered in this study. On the other hand, when high-ranked individuals were removed from the flock, low-ranked sheep shifted their selection patterns by increasing the use of the most preferred areas and strongly avoided to use less preferred sites (i.e., a highly selective grazing behaviour). Discussion. Although homogenization and segregation of flocks by classes are common practices to increase flock productivity, we are proposing an alternative that employs behavioural interactions in heterogeneous flocks to generate more evenly distributed grazing patterns. This practice can be combined with other practices such as rotational grazing and guardian dogs (to decrease mortality levels that may be generated by sheep grazing on more risky habitats). This does not imply any modifications of livestock stocking rates and densities or any additional investments for labour and materials. Considering livestock behaviour is critical for the design of sustainable management practices that balance landscape conservation and livestock productivity. PMID- 27366651 TI - Does our legal minimum drinking age modulate risk of first heavy drinking episode soon after drinking onset? Epidemiological evidence for the United States, 2006 2014. AB - Background. State-level 'age 21' drinking laws conform generally with the United States National Minimum Drinking Age Act of 1984 (US), and are thought to protect young people from adverse drinking experiences such as heavy episodic drinking (HED, sometimes called 'binge drinking'). We shed light on this hypothesis while estimating the age-specific risk of transitioning from 1st full drink to 1st HED among 12-to-23-year-old newly incident drinkers, with challenge to a "gender gap" hypothesis and male excess described in HED prevalence reports. Methods. The study population consisted of non-institutionalized civilians in the United States, with nine independently drawn nationally representative samples of more than 40,000 12-to-23-year-olds (2006-2014). Standardized audio computer-assisted self-interviews identified 43,000 newly incident drinkers (all with 1st HED evaluated within 12 months of drinking onset). Estimated age-specific HED risk soon after first full drink is evaluated for males and females. Results. Among 12 to-23-year-old newly incident drinkers, an estimated 20-30% of females and 35-45% of males experienced their 1st HED within 12 months after drinking onset. Before mid-adolescence, there is no male excess in such HED risk. Those who postponed drinking to age 21 are not spared (27% for 'postponer' females; 95% CI [24-30]; 42% for 'postponer' males; 95% CI [38-45]). An estimated 10-18% females and 10 28% males experienced their 1st HED in the same month of their 1st drink; peak HED risk estimates are 18% for 'postponer' females (95% CI [15-21]) and 28% for 'postponer' males (95% CI [24-31]). Conclusions. In the US, one in three young new drinkers transition into HED within 12 months after first drink. Those who postpone the 1st full drink until age 21 are not protected. Furthermore, 'postponers' have substantial risk for very rapid transition to HED. A male excess in this transition to HED is not observed until after age 14. PMID- 27366652 TI - Five new species and one new genus of recent miliolid foraminifera from Raja Ampat (West Papua, Indonesia). AB - Raja Ampat is an archipelago of about 1,500 small islands located northwest off the Bird's Head Peninsula of Indonesia's West Papua province. It is part of the Coral Triangle, a region recognized as the "epicenter" of tropical marine biodiversity. In the course of a large-scale survey on shallow benthic foraminifera we have discovered one new genus and five new species of recent miliolid benthic foraminifera from the highly diverse reefal and nearshore environments. The new fischerinid genus Dentoplanispirinella is characterized by its planispiral coiling and by the presence of a simple tooth, that differentiate it from Planispirinella Wiesner. It is represented in our sample material by the new species Dentoplanispirinella occulta. The other four species described herein are Miliolinella moia, Miliolinella undina, Triloculina kawea and Siphonaperta hallocki. All new species are comparatively rare and occur sporadically in the sample material. Detailed morphological descriptions, scanning electron microscopy pictures of complete and dissected specimens as well as micro-computed tomography images are provided. PMID- 27366653 TI - Stochasticity in space, persistence in time: genetic heterogeneity in harbour populations of the introduced ascidian Styela plicata. AB - Spatio-temporal changes in genetic structure among populations provide crucial information on the dynamics of secondary spread for introduced marine species. However, temporal components have rarely been taken into consideration when studying the population genetics of non-indigenous species. This study analysed the genetic structure of Styela plicata, a solitary ascidian introduced in harbours and marinas of tropical and temperate waters, across spatial and temporal scales. A fragment of the mitochondrial gene Cytochrome Oxidase subunit I (COI) was sequenced from 395 individuals collected at 9 harbours along the NW Mediterranean coast and adjacent Atlantic waters (> 1,200 km range) at two time points 5 years apart (2009 and 2014). The levels of gene diversity were relatively low for all 9 locations in both years. Analyses of genetic differentiation and distribution of molecular variance revealed strong genetic structure, with significant differences among many populations, but no significant differences among years. A weak and marginally significant correlation between geographic distance and gene differentiation was found. Our results revealed spatial structure and temporal genetic homogeneity in S. plicata, suggesting a limited role of recurrent, vessel-mediated transport of organisms among small to medium-size harbours. Our study area is representative of many highly urbanized coasts with dense harbours. In these environments, the episodic chance arrival of colonisers appears to determine the genetic structure of harbour populations and the genetic composition of these early colonising individuals persists in the respective harbours, at least over moderate time frames (five years) that encompass ca. 20 generations of S. plicata. PMID- 27366654 TI - Preserving and vouchering butterflies and moths for large-scale museum-based molecular research. AB - Butterflies and moths (Lepidoptera) comprise significant portions of the world's natural history collections, but a standardized tissue preservation protocol for molecular research is largely lacking. Lepidoptera have traditionally been spread on mounting boards to display wing patterns and colors, which are often important for species identification. Many molecular phylogenetic studies have used legs from pinned specimens as the primary source for DNA in order to preserve a morphological voucher, but the amount of available tissue is often limited. Preserving an entire specimen in a cryogenic freezer is ideal for DNA preservation, but without an easily accessible voucher it can make specimen identification, verification, and morphological work difficult. Here we present a procedure that creates accessible and easily visualized "wing vouchers" of individual Lepidoptera specimens, and preserves the remainder of the insect in a cryogenic freezer for molecular research. Wings are preserved in protective holders so that both dorsal and ventral patterns and colors can be easily viewed without further damage. Our wing vouchering system has been implemented at the University of Maryland (AToL Lep Collection) and the University of Florida (Florida Museum of Natural History, McGuire Center of Lepidoptera and Biodiversity), which are among two of the largest Lepidoptera molecular collections in the world. PMID- 27366655 TI - Determinants of acute mortality of Hippodamia convergens (Coleoptera: Coccinellidae) to ultra-low volume permethrin used for mosquito management. AB - There are relatively few experimental studies and risk assessments of the effects on non-target insects from ultra-low volume (ULV) insecticides used for management of adult mosquitoes. Therefore, we evaluated factors that may influence the ability of an insect to intercept the insecticide at the time of application by using Hippodamia convergens (Coleoptera: Coccinellidae) in field bioassay experiments in 2011 and 2015. Treatment factors included different distances, two cage heights (ground-level and 1.5 m above ground) to the point of the application, and covered vs. uncovered cage faces (2015 only). Insecticides used included a water-based formulation (Aqua-Reslin(r)) and an oil-based formulation (Permanone(r) 30-30) of permethrin. Cage height was highly significant both years, with much less acute (i.e., short-term exposure) mortality at ground-level compared with 1.5 m. In 2011, acute mortality was less at ground-level (mean = 3.2%, median = 0%) compared to 1.5 m (mean = 85.2%, median = 100%). Cage type also was highly significant, with less mortality in covered cages compared to uncovered cages. Mortality by cage height and cage type was as follows: ground level, covered cage (mean = 2.8%, median = 0.1%); ground level, uncovered cage (mean = 41.9%, median = 9.6%); 1.5 m, covered cage (mean = 6.8%, median = 0%); 1.5 m, uncovered cage (mean = 83.7%, median = 100%). Results suggest that acute mortality to non-target insects may vary considerably based on their height and their ability to directly intercept the insecticide as the aerosol passes through the area being sprayed. PMID- 27366656 TI - Local avian density influences risk of mortality from window strikes. AB - Up to a billion birds die per year in North America as a result of striking windows. Both transparent and reflective glass panes are a cause for concern, misleading birds by either acting as invisible, impenetrable barriers to desired resources, or reflecting those resources over a large surface area. A high number of window strikes occur during migration, but little is known about the factors of susceptibility, or whether particular avian taxa are more vulnerable than others. We report on a study of window strikes and mist-netting data at the Virginia Zoological Park (Norfolk, Virginia, USA), conducted in the autumn of 2013 and 2014. We focused on three factors likely to contribute to an individual's predisposition to collide with windows: (i) taxonomic classification, (ii) age, and (iii) migrant vs. resident status. Thrushes, dominated by the partial migrant American Robin (Turdus migratorius), were significantly less likely to strike glass than be sampled in mist nets (chi(2) = 9.21, p = 0.002), while wood-warblers (Parulidae) were more likely to strike than expected (chi(2) = 13.55, p < 0.001). The proportion of juveniles striking windows (45.4%) was not significantly different (chi(2) = 0.05, p = 0.827) than the population of juvenile birds naturally occurring at the zoo (48.8%). Migrants, however, were significantly more susceptible to window strikes than residents (chi(2) = 6.35, p = 0.012). Our results suggest that resident birds are able to learn to avoid and thus reduce their likelihood of striking windows; this intrinsic risk factor may help explain the apparent susceptibility of certain taxa to window strikes. PMID- 27366657 TI - Association Between Lipid Biomarkers, Physical Activity, and Socioeconomic Status in a Population-Based Cross-Sectional Study in the UK. AB - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of global death. Physical activity can help individuals reduce their CVD risk. However, the biological mechanisms explaining the link between physical activity and CVD risk and how they may be mediated by socioeconomic status are not well understood. METHODS: We use cross-sectional data from 2010/2011 of the Understanding Society Survey, UK, to investigate the association between two biomarkers for CVD risk: cholesterol ratio and triglyceride levels and four different measures of physical activity: moderate, mild, self-reported activity rating, and walking 30 min or more a week using multivariate logistic regression. The analysis investigates if this association is mediated by socioeconomic status and difficulty accessing sports facilities. RESULTS: Results from multivariate regressions show that moderate and self-reported activity rating are significantly associated with cholesterol ratio and triglycerides for both men and women. A weaker association was found for walking 30 min or more a week. No association was found between mild physical activity and the two biomarkers. There is some evidence that socioeconomic status mediates the relationship between the biomarkers and physical activity. A significant association between socioeconomic status variables and the biomarkers was found only for women. CONCLUSIONS: We provide some evidence of the mechanisms explaining the link between CVD risk and physical activity by finding an association with traditional lipid biomarkers. We also find that intensity of physical activity matters. Socioeconomic status especially for women is important which may explain some of the inequalities in CVD risk. PMID- 27366658 TI - Eliciting and Measuring Betrayal Aversion using the BDM Mechanism. AB - Betrayal aversion has been operationalized as the evidence that subjects demand a higher risk premium to take social risks compared to natural risks. This evidence has been first shown by Bohnet and Zeckhauser (2004) using an adaptation of the Becker - DeGroot - Marschak mechanism (BDM, Becker et al. (1964)). We compare their implementation of the BDM mechanism with a new version designed to facilitate subjects' comprehension. We find that, although the two versions produce different distributions of values, the size of betrayal aversion, measured as an average treatment difference between social and natural risk settings, is not different across the two versions. We further show that our implementation is preferable to use in practice as it reduces substantially subjects' mistakes and the likelihood of noisy valuations. PMID- 27366659 TI - Genetic diagnosis of autosomal dominant polycystic kidney disease: linkage analysis versus direct mutation analysis. PMID- 27366661 TI - Changes in urinary potassium excretion in patients with chronic kidney disease. AB - BACKGROUND: Hyperkalemia is one of the more serious complications of chronic kidney disease (CKD), and the cause of potassium retention is a reduction in urinary potassium excretion. However, few studies have examined the extent of the decrease of urinary potassium excretion in detail with respect to decreased renal function. METHODS: Nine hundred eighty-nine patients with CKD (CKD stages G1 and G2 combined: 135; G3a: 107; G3b: 170; G4: 289; and G5: 288) were evaluated retrospectively. Values for urinary potassium excretion were compared between CKD stages, and the associations between urinary potassium excretion and clinical parameters, including diabetes mellitus status and use of renin-angiotensin aldosterone system inhibitors, were analyzed using a multivariable linear regression analysis. RESULTS: Urinary potassium excretion gradually decreased with worsening of CKD (G5: 24.8 +/- 0.8 mEq/d, P < 0.001 vs. earlier CKD stages). In contrast, the value of fractional excretion of potassium at CKD G5 was significantly higher than that at the other stages (30.63 +/- 0.93%, P < 0.001). Multivariable linear regression analysis revealed that urinary potassium excretion was independently associated with urinary sodium excretion (standardized coefficient, 0.499), the estimated glomerular filtration rate (0.281), and serum chloride concentration (-0.086). CONCLUSION: This study demonstrated that urinary potassium excretion decreased with reductions in renal function. Furthermore, urinary potassium excretion was mainly affected by urinary sodium excretion and estimated glomerular filtration rate in patients with CKD, whereas the presence of diabetes mellitus and use of renin-angiotensin aldosterone system inhibitors were not associated with urinary potassium excretion in this study. PMID- 27366660 TI - Adenosine monophosphate-activated protein kinase in diabetic nephropathy. AB - Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and its pathogenesis is complex and has not yet been fully elucidated. Abnormal glucose and lipid metabolism is key to understanding the pathogenesis of DN, which can develop in both type 1 and type 2 diabetes. A hallmark of this disease is the accumulation of glucose and lipids in renal cells, resulting in oxidative and endoplasmic reticulum stress, intracellular hypoxia, and inflammation, eventually leading to glomerulosclerosis and interstitial fibrosis. There is a growing body of evidence demonstrating that dysregulation of 5' adenosine monophosphate-activated protein kinase (AMPK), an enzyme that plays a principal role in cell growth and cellular energy homeostasis, in relevant tissues is a key component of the development of metabolic syndrome and type 2 diabetes mellitus; thus, targeting this enzyme may ameliorate some pathologic features of this disease. AMPK regulates the coordination of anabolic processes, with its activation proven to improve glucose and lipid homeostasis in insulin-resistant animal models, as well as demonstrating mitochondrial biogenesis and antitumor activity. In this review, we discuss new findings regarding the role of AMPK in the pathogenesis of DN and offer suggestions for feasible clinical use and future studies of the role of AMPK activators in this disorder. PMID- 27366662 TI - The successful clinical outcomes of pregnant women with advanced chronic kidney disease. AB - BACKGROUND: Successful pregnancy outcomes in patients with advanced chronic kidney disease (CKD) are increasingly common in Western countries. However, in Korea, the available literature addressing this clinical issue is scarce. METHODS: We reviewed 5 successful parturitions [1 patient with Stage 5 CKD and 4 with maintenance hemodialysis (HD)] at Seoul St. Mary's Hospital over 3 years and investigated changes in dialysis prescription, anemia management, and the incidence of maternal and neonatal complications. RESULTS: There were no maternal or neonatal deaths in this cohort. The mean age at the time of conception and delivery was 35.8 +/- 3.7 and 36.2 +/- 3.5 years, respectively. Dialysis patients received more frequent and intensified HD during pregnancy, 20.0 +/- 5.7 h/wk of HD over 5 visits with the ultrafiltration dose maintained between 1 and 2 kg per session. All patients received erythropoietin-stimulating agents and iron replacement therapy during pregnancy. The mean hematocrit was 33.1 +/- 1.9% before pregnancy and was well maintained during gestation (33.9 +/- 3.8% at the first trimester, 29.2 +/- 4.2% at the second trimester, and 33.6 +/- 8.7% at delivery). The mean gestation period was 32.7 +/- 4.7 weeks, with 60% of patients experiencing premature delivery. The primary maternal complication was pre eclampsia; 3 women developed pre-eclampsia and underwent emergency cesarean sections. Most neonatal complications were related to preterm birth. CONCLUSION: Dialysis-related care and general clinical management improved the clinical outcome of pregnancy for patients with advanced CKD. PMID- 27366663 TI - Risk factors and outcomes of acute renal infarction. AB - BACKGROUND: Renal infarction (RI) is an uncommon disease that is difficult to diagnose. As little is known about clinical characteristics of this disease, we investigated its underlying risk factors and outcomes. METHODS: We performed a retrospective single-center study of 89 patients newly diagnosed with acute RI between January 2002 and March 2015 using imaging modalities. Clinical features, possible etiologies, and long-term renal outcome data were reviewed. RESULTS: The patients' mean age was 63.5 +/- 15.42 years; 23.6% had diabetes and 56.2% had hypertension. Unilateral and bilateral involvements were shown in 80.9% and 19.1% of patients, respectively; proteinuria and hematuria were reported in 40.4% and 41.6%, respectively. Cardiovascular disease was the most common underlying disease, followed by renal vascular injury and hypercoagulability disorder. Fourteen patients had no specific underlying disease. At the time of diagnosis, acute kidney injury (AKI) was found in 34.8% of patients. Univariate analysis revealed diabetes mellitus (DM), leukocytosis, and high C-reactive protein (CRP) as significant risk factors for the development of AKI. On multivariate analysis, DM and high CRP levels were independent predictors for AKI. During follow-up, chronic kidney disease developed in 27.4% of patients. Univariate and multivariate Cox regression analyses showed old age to be an independent risk factor for this disease, whereas AKI history was a negative risk factor. CONCLUSION: DM patients or those with high CRP levels should be observed for renal function deterioration. Clinicians should also monitor for RI in elderly patients. PMID- 27366664 TI - PKD2 mutation in an Iranian autosomal dominant polycystic kidney disease family with misleading linkage analysis data. AB - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic renal disorder caused by mutation in 2 genes PKD1 and PKD2. Thus far, no mutation is identified in approximately 10% of ADPKD families, which can suggest further locus heterogeneity. Owing to the complexity of direct mutation detection, linkage analysis can initially identify the responsible gene in appropriate affected families. Here, we evaluated an Iranian ADPKD family apparently unlinked to both PKD1 and PKD2 genes. This is one of the pioneer studies in genetic analysis of ADPKD in Iranian population. METHODS: Linkage reanalysis was performed by regenotyping of flanking microsatellite markers in 8 individuals of the ADPKD family. Direct mutation analysis was performed by Sanger sequencing. RESULTS: Mutation analysis revealed a pathogenic mutation (c.1094+1G>A) in the PKD2 gene in the proband. Analyzing 2 healthy and 4 clinically affected members confirmed the correct segregation of the mutation within the family and also ruled out the disease in 1 suspected individual. Misinterpretation of the linkage data was due to the occurrence of 1 crossing over between the PKD2 intragenic and the nearest downstream marker (D4S2929). Homozygosity of upstream markers caused the recombination indistinguishable. CONCLUSION: Although analysis of additive informative polymorphic markers can overcome the misleading haplotype data, it is limited because of the lack of other highly polymorphic microsatellite markers closer to the gene. Direct mutation screening can identify the causative mutation in the apparently unlinked pedigree; moreover, it is the only approach to achieve the confirmed diagnosis in individuals with equivocal imaging results. PMID- 27366665 TI - Predicting the probability of survival in acute paraquat poisoning. AB - BACKGROUND: Paraquat (PQ) concentration-time data have been used to predict prognosis for 3 decades. The aim of this study was to find a more accurate method to predict the probability of survival. METHODS: This study included 788 patients with PQ poisoning who were diagnosed using plasma PQ concentration between January 2005 and August 2012. We divided these patients into 2 groups (survivors vs. nonsurvivors), compared their clinical characteristics, and analyzed the predictors of survival. RESULTS: The mean age of the included patients was 57 years (range, 14-95 years). When we compared clinical characteristics between survivors (n = 149, 19%) and nonsurvivors (n = 639, 81%), survivors were younger (47 +/- 14 years vs. 59 +/- 16 years) and had lower plasma PQ concentrations (1.44 +/- 8.77 MUg/mL vs. 80.33 +/- 123.15 MUg/mL) than nonsurvivors. On admission, serum creatinine was lower in survivors than in nonsurvivors (0.95 +/- 0.91 mg/dL vs. 1.88 +/- 1.27 mg/dL). In multivariate logistic regression analysis, age and logarithmically converted serum creatinine [ln(Cr)], [ln(time)], and [ln(PQ)] were assessed as prognostic factors to predict survival in PQ poisoning. The predicted probability of survival using significant prognostic factors was exp (logit)/[1 + exp(logit)], where logit = -1.347 + [0.212 * sex (male = 1, female = 0)] + (0.032 * age) + [1.551 * ln(Cr)] + [0.391 * ln(hours since ingestion)] + [1.076 * ln(plasma PQ MUg/mL)]. With this equation, the sensitivity and specificity were 86.5% and 98.7%, respectively. CONCLUSION: Age, ln(Cr), ln(time), and ln(PQ) were important prognostic factors in PQ poisoning, and our equation can be helpful to predict the survival in acute PQ poisoning patients. PMID- 27366666 TI - Comparison of uremic pruritus between patients undergoing hemodialysis and peritoneal dialysis. AB - BACKGROUND: Uremic pruritus is a common, but unpleasant, complication of end stage renal disease. The uremic burden may differ between hemodialysis (HD) and peritoneal dialysis (PD) patients. This difference may also change the clinical characteristics of uremic pruritus between the 2 modalities. In this study, we investigated the uremic pruritus between patients on HD and PD. METHODS: A total of 425 HD and 223 PD patients from the Clinical Research Center registry in Korea were included. Patients were assessed for pruritus intensity, scratching activity, pruritus distribution, and frequency of pruritus-related sleep disturbance using the visual analog scale and questionnaire. RESULTS: The prevalence of uremic pruritus was higher in PD patients than that in HD patients (62.6% vs. 48.3%, P = 0.001). In the multivariable logistic analysis, PD treatment was significantly associated with the prevalence of uremic pruritus (odds ratio, 1.76; 95% confidence interval, 1.20-2.57, P = 0.004) after adjustment for clinical variables. The visual analog scale score, representing a subjective intensity of itchiness, was significantly higher in PD patients (PD 2.11 +/- 2.32 vs. HD 1.65 +/- 2.28, P = 0.013) compared with HD patients. The intensity of uremic pruritus was independently related with serum albumin levels (beta = -0.143, P = 0.006) in HD patients and total weekly Kt/V (beta = -0.176, P = 0.028) in PD patients. CONCLUSION: Our data demonstrate the difference in prevalence, intensity, and risk factors of uremic pruritus between HD and PD patients. These findings suggest that careful consideration for uremic pruritus might be needed in end-stage renal disease patients according to the dialysis modality. PMID- 27366667 TI - Clinical significance of red blood cell distribution width in the prediction of mortality in patients on peritoneal dialysis. AB - BACKGROUND: In this study, we assessed whether red blood cell distribution width (RDW) was associated with all-cause mortality in patients on peritoneal dialysis (PD) and evaluated its prognostic value. METHODS: This study included 136 patients who had RDW levels at PD initiation from January 2007 to January 2014 at the Presbyterian Medical Center and Seoul St. Mary's Hospital. We divided these patients into 2 groups (survivors vs. nonsurvivors), compared their clinical characteristics, and analyzed the predictors of survival. RESULTS: The study included 79 men and 57 women, with a mean age of 54 years (range, 15-85 years). The mean follow-up duration was 32 months (range, 1-80 months). Of 136 patients, 14 died during the follow-up period. When clinical characteristics of survivors (n = 122) and nonsurvivors (n = 14) were compared, no differences were identified, with the exception of serum albumin, total iron-binding capacity (TIBC), left ventricular ejection fraction, total leukocyte count, and RDW value. Survivors had higher serum albumin (3.4 +/- 0.5 vs. 3.0 +/- 0.5 g/dL, P < 0.001) and left ventricular ejection fraction (56.8 +/- 9.8 vs. 48.7 +/- 12.8, P = 0.040) and lower TIBC (213.4 +/- 40.9 vs. 252.8 +/- 65.6, P = 0.010), total leukocyte counts (6.9 * 10(3)/MUL vs. 8.6 * 10(3)/MUL, P = 0.009), and serum RDW values (13.9 +/- 1.7 vs. 16.0 +/- 1.8, P < 0.001). Patients with high RDW levels (>= 14.8) showed significantly higher all-cause mortality than patients with low RDW levels (< 14.8, P < 0.001). In multivariate-adjusted Cox analysis, RDW and TIBC at the start of PD were independent risk predictors for all-cause mortality. CONCLUSION: RDW could be an additive predictor for all-cause mortality in patients on PD. PMID- 27366668 TI - Renal artery stenosis presenting with nephrotic-range proteinuria: a case report. AB - Renal artery stenosis (RAS) is commonly presented with hypertension and chronic kidney disease. We report a rare case of RAS occurring in a 78-year-old man who presented with nephrotic-range proteinuria. Renal biopsy on the left side was performed, and results showed mesangiopathic glomerulonephritis, which was not compatible with the cause of nephrotic-range proteinuria. Proteinuria was decreased by angiotensin receptor blocker, but azotemia was aggravated. Therefore, angiotensin receptor blocker was discontinued inevitably and thorough evaluation for the possibility of RAS was performed. Computed tomography angiography revealed significant RAS on the left side and a renal artery stent was inserted. After stenting, aortic dissection developed and progressed despite tight control of blood pressure. After inserting another stent graft through the true lumen of the left renal artery, the patient's renal function and proteinuria improved markedly. PMID- 27366669 TI - Successfully treated isolated renal artery pseudoaneurysm in a patient with Behcet's disease. AB - Renal artery aneurysms and pseudoaneurysms are an uncommon clinical problem with a low incidence rate. They are abnormal dilatations of the vessel lumen with some different natures. However, the rupture of an aneurysm and pseudoaneurysm is the most dreaded complication because it causes death of the patient. There are many causes of renal artery aneurysm and pseudoaneurysm, including Behcet's disease; however, renal involvement in Behcet's disease is less frequent. We report a case of renal artery pseudoaneurysm induced by Behcet's disease and treated successfully with coil embolization. A 56-year-old woman with Behcet's disease presented with an incidental left renal artery pseudoaneurysm measuring 18 mm. We successfully performed endovascular treatment with coil embolization instead of surgical treatment. PMID- 27366670 TI - Relapsing lupus enteritis in systemic lupus erythematosus. PMID- 27366671 TI - Is hypomagnesemia associated with using proton pump inhibitors? PMID- 27366672 TI - Erratum: RNA sequencing of the nephron transcriptome: a technical note [Volume 34, Issue 4, December 2015, Pages 219-227]. AB - [This corrects the article DOI: 10.1016/j.krcp.2015.08.008.]. PMID- 27366673 TI - Everolimus associated interstitial pneumonitis in a liver transplant patient. AB - Drug-induced interstitial lung disease is associated with significant morbidity and mortality. Everolimus is an inhibitor of mTOR, a mammalian target of rapamycin, used as an immunosuppressant agent in solid organ transplant. Everolimus has been associated with interstitial lung disease in solid organ transplant patients but has been rarely reported in the liver transplant patient population. We report a case of interstitial pneumonitis in a liver transplant patient associated with everolimus which completely resolved after discontinuation of the medication. PMID- 27366674 TI - Seroprevalence of Borrelia burgdorferi antibodies in white-tailed deer from Texas. AB - Lyme Disease is caused by the bacterial pathogen Borrelia burgdorferi, and is transmitted by the tick-vector Ixodes scapularis. It is the most prevalent arthropod-borne disease in the United States. To determine the seroprevalence of B. burgdorferi antibodies in white-tailed deer (Odocoileus virginianus) from Texas, we analyzed serum samples (n = 1493) collected during the 2001-2015 hunting seasons, using indirect ELISA. Samples with higher sero-reactivity (0.803 and above) than the negative control group (0.662) were further tested using a more specific standardized western immunoblot assay to rule out false positives. Using ELISA, 4.7% of the samples were sero-reactive against B. burgdorferi, and these originated in two eco-regions in Texas (Edwards Plateau and South Texas Plains). However, only 0.5% of the total samples were sero-reactive by standardized western immunoblot assay. Additionally, both ELISA and standardized western immunoblot assay results correlated with an increased incidence in human Lyme Disease cases reported in Texas. This is the first longitudinal study to demonstrate fluctuation in sero-reactivity of white-tailed deer to B. burgdorferi sensu stricto antigens in southern United States. Future ecological and geographical studies are needed to assess the environmental factors governing the prevalence of Lyme Disease in non-endemic areas of the southern United States. PMID- 27366675 TI - NGS-based deep bisulfite sequencing. AB - We have developed an NGS-based deep bisulfite sequencing protocol for the DNA methylation analysis of genomes. This approach allows the rapid and efficient construction of NGS-ready libraries with a large number of PCR products that have been individually amplified from bisulfite-converted DNA. This approach also employs a bioinformatics strategy to sort the raw sequence reads generated from NGS platforms and subsequently to derive DNA methylation levels for individual loci. The results demonstrated that this NGS-based deep bisulfite sequencing approach provide not only DNA methylation levels but also informative DNA methylation patterns that have not been seen through other existing methods.*This protocol provides an efficient method generating NGS-ready libraries from individually amplified PCR products.*This protocol provides a bioinformatics strategy sorting NGS-derived raw sequence reads.*This protocol provides deep bisulfite sequencing results that can measure DNA methylation levels and patterns of individual loci. PMID- 27366677 TI - Endothelial nitric oxide synthase deficiency influences normal cell cycle progression and apoptosis in trabecular meshwork cells. AB - AIM: To clarify how the endothelial nitric oxide synthase (eNOS, NOS3) make effect on outflow facility through the trabecular meshwork (TM). METHODS: Inhibition of NOS3 gene expression in human TM cells were conducted by three siRNAs. Then the mRNA and protein levels of NOS3 in siRNA-treated and negative control (NC) cells were determined, still were the collagen, type IV, alpha 1 (COL4A1) and fibronectin 1 by real-time PCR and Western blot analysis. In addition, NOS3 concentrations in culture supernatant fluids of TM cells were measured. Cell cycle and cell apoptosis analysis were performed using flow cytometry. RESULTS: The mRNA level of NOS3 was decreased by three different siRNA interference, similar results were obtained not only of the relative levels of NOS3 protein, but also the expression levels of COL4A1 and fibronectin 1. The number of cells in S phase was decreased, while contrary result was obtained in G2 phase. The number of apoptotic cells in siRNA-treated groups were significant increased compared to the NC samples. CONCLUSION: Abnormal NOS3 expression can make effects on the proteins levels of extracellular matrix component (e.g. fibronectin 1 and COL4A1). Reduced NOS3 restrains the TM cell cycle progression at the G2/M-phase transition and induced cell apoptosis. PMID- 27366676 TI - Inclusion of emerging organic contaminants in groundwater monitoring plans. AB - Groundwater is essential for human life and its protection is a goal for the European policies. All the anthropogenic activities could impact on water quality. *Conventional pollutants and more than 700 emerging pollutants, resulting from point and diffuse source contamination, threat the aquatic ecosystem.*Policy-makers and scientists will have to cooperate to create an initial groundwater emerging pollutant priority list, to answer at consumer demands for safety and to the lack of conceptual models for emerging pollutants in groundwater.*Among the emerging contaminants and pollutants this paper focuses on organic wastewater contaminants (OWCs) mainly released into the environment by domestic households, industry, hospitals and agriculture. This paper starts from the current regulatory framework and from the literature overview to explain how the missing conceptual model for OWCs could be developed.*A full understanding of the mechanisms leading to the contamination and the evidence of the contamination must be the foundation of the conceptual model. In this paper carbamazepine, galaxolide and sulfamethozale, between the OWCs, are proposed as "environmental tracers" to identify sources and pathways ofcontamination/pollution. PMID- 27366678 TI - Matrix metalloproteinase-9 and vascular endothelial growth factor expression change in experimental retinal neovascularization. AB - AIM: To investigate the signal transduction mechanism of matrix metalloproteinase 9 (MMP-9) mediated- vascular endothelial growth factor (VEGF) expression and retinal neovascularization (RNV) in oxygen-induced retinopathy (OIR) model. METHODS: C57BL/6J mice were divided into four groups: control group, OIR group, OIR control group (phosphate-buffered saline by intravitreal injection) and treated group [tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) by intravitreal injection]. OIR model was established in C57BL/6J mice exposed to 75%+/-2% oxygen for 5d. mRNA level and protein expression of MMP-9, TIMP-1 and VEGF were measured by real-time polymerase chain reaction and Western blotting, and located by immunohistochemistry. RESULTS: Levels of MMP-9 and VEGF in retina were significantly increased in animals with OIR and OIR control group. Levels of TIMP-1 in retina was significantly reduced in animals with OIR and OIR control group. Furthermore, a significant correlation was found between MMP-9 and VEGF. Intravitreal injection of TIMP-1 significantly reduced MMP-9 and VEGF expression of the OIR mouse model (all P<0.05). CONCLUSION: These results demonstrate that MMP-9-mediated up-regulation of VEGF promotes RNV in retinopathy of prematurity (ROP). TIMP-1 may be a potential target for the prevention and treatment of ROP. PMID- 27366679 TI - Repression of retinal microvascular endothelial cells by transthyretin under simulated diabetic retinopathy conditions. AB - AIM: To investigate biological effects of transthyretin (TTR) on the development of neovascularization under simulated diabetic retinopathy (DR) condition associated with high glucose and hypoxia. METHODS: Human retinal microvascular endothelial cells (hRECs) were cultured in normal and simulated DR environments with high glucose and hypoxia. The normal serum glucose concentration is approximately 5.5 mmol/L; thus, hyperglycemia was simulated with 25 mmol/L glucose, while hypoxia was induced using 200 umol/L CoCl2. The influence of TTR on hRECs and human retinal pigment epithelial cells (hRPECs) was determined by incubating the cells with 4 umol/L TTR in normal and abnormal media. A co-culture system was then employed to evaluate the effects of hRPECs on hRECs. RESULTS: Decreased hRECs and hRPECs were observed under abnormal conditions, including high-glucose and hypoxic media. In addition, hRECs were significantly inhibited by 4 umol/L exogenous TTR during hyperglycemic culture. During co-culture, hRPECs inhibited hRECs in both the normal and abnormal environments. CONCLUSION: hREC growth is inhibited by exogenous TTR under simulated DR environments with high glucose and hypoxic, particularly in the medium containing 25 mmol/L glucose. hRPECs, which manufacture TTR in the eye, also represses hRECs in the same environment. TTR is predicted to inhibit the proliferation of hRECs and neovascularization. PMID- 27366680 TI - Histopathological changes in retinas and F-ERG features of streptozotocin-induced diabetic rats treated with ozone. AB - AIM: To study the histopathological changes in the retina and flash electroretinogram (F-ERG) features of ozone-treated streptozotocin (STZ)-induced diabetic rats. METHODS: Seventy male Sprague Dawley rats were grouped as follows: blank group (GB, n=10), model control group (GM, n=18), ozone group (GO3, n=19), and oxygen group (GO2, n=18). The model was induced by single intraperitoneal injection of STZ. Ozone or oxygen enteroclysm was given twice per week for 4wk. F ERG and histopathological examinations were performed one month after treatment. RESULTS: Under dark adaption, as compared to GB, the other groups each had differential decreases in the a-wave amplitudes (P<0.05); the latencies were delayed in GM, GO2, and GO3 rats (P<0.05). Similar results were observed under light adaption, with the exception that the a-wave of the amplitudes (F=0.28, P>0.05). There were significant differences in the apoptosis index among the groups (P<0.05). Under ozone treatment, apoptosis was decreased in GO3 as compared to GM and GO2. CONCLUSION: Ozone administration alleviates nerve damage and reduces pathology and apoptosis in the retinas of diabetic rats. PMID- 27366681 TI - Effect of periocular injection of celecoxib and propranolol on ocular level of vascular endothelial growth factor in a diabetic mouse model. AB - AIM: To investigate the effects of periocular injection of propranolol and celecoxib on ocular levels of vascular endothelial growth factor (VEGF) in a diabetic mouse model. METHODS: Forty 4-6wk BALB-C male mice weighing 20-25 g were used. The study groups included: non-diabetic control (group 1), diabetic control (group 2), diabetic propranolol (group 3), and diabetic celecoxib (group 4). After induction of type 1 diabetes by streptozotocin, propranolol (10 ug) and celecoxib (200 ug dissolved in carboxymethylcellulose 0.5%) were injected periocularly. The ocular level of VEGF was measured in all the study groups using enzyme-linked immuno sorbent assay (ELISA) method. RESULTS: Ocular VEGF level was significantly increased (1.25 fold) in the diabetic control group when compared to the non-diabetic group one week after induction with streptozotocin (P=0.002). Both periocular propranolol and celecoxib significantly reduced ocular VEGF levels (P=0.047 and P<0.001, respectively). The effect was more pronounced with celecoxib. CONCLUSION: The periocular administration of propranolol and celecoxib can significantly reduce ocular VEGF levels in a diabetic mouse model. PMID- 27366682 TI - Effect of long-term weightlessness on retina and optic nerve in tail-suspension rats. AB - AIM: To evaluate the effect of long-term weightlessness on retina and optic nerve in tail-suspension (TS) rats. METHODS: A stimulated weightlessness model was established by suspending rats' tail. After 12wk, the ultrastructure and the number of optic nerve axons were observed by transmission electron microscope. The number of survival retinal ganglion cells (RGCs) was calculated by fluorescent gold retrograde labeling. Retina cells apoptosis was detected by TUNEL staining. The function of optic nerve and retina was evaluated by the visual evoked potential (VEP) and oscillatory potentials (Ops). RESULTS: The optic nerve axons were swollen and sparsely aligned, and the lamellar separation and myelin disintegration occurred after 12wk in TS rats. The density of optic nerve axons was 32.23+/-3.92 (vs 37.43+/-4.13, P=0.0145), the RGCs density was 1645+/-46 cells/mm(2) (vs 1867+/-54 cells/mm(2) P=0.0000), the incidence rate of retinal cells apoptosis was 5.38%+/-0.53% (vs 4.75%+/-0.54%, P=0.0238), the amplitude of VEP-P100 was 15.43+/-2.14 uV (vs 17.67+/-2.17 uV, P=0.0424), the latency of VEP-P100 was 69.05+/-5.34ms (vs 62.43+/-4.87ms P=0.0143) and the sum amplitude of Ops was 81.05+/-8.34 uV (vs 91.67+/-10.21 uV, P=0.0280) in TS group and the control group, respectively. CONCLUSION: Long-term weightlessness can induce the ultrastructural changes and functional depress of the optic nerve, as well as retinal cell damages in TS rats. PMID- 27366683 TI - Role of tumor necrosis factor-alpha in zebrafish retinal neurogenesis and myelination. AB - AIM: To investigate the role of tumor necrosis factor-alpha (TNF-alpha) in zebrafish retinal development and myelination. METHODS: Morpholino oligonucleotides (MO), which are complementary to the translation start site of the wild-type embryonic zebrafish TNF-alpha mRNA sequence, were synthesized and injected into one- to four-cell embryos. The translation blocking specificity was verified by Western blotting using an anti-TNF-alpha antibody, whole-mount in situ hybridization using a hepatocyte-specific mRNA probe ceruloplasmin (cp), and co-injection of TNF-alpha MO and TNF-alpha mRNA. An atonal homolog 7 (atoh7) mRNA probe was used to detect neurogenesis onset. The retinal neurodifferentiation was analyzed by immunohistochemistry using antibodies Zn12, Zpr1, and Zpr3 to label ganglion cells, cones, and rods, respectively. Myelin basic protein (mbp) was used as a marker to track and observe the myelination using whole-mount in situ hybridization. RESULTS: Targeted knockdown of TNF-alpha resulted in specific suppression of TNF-alpha expression and a severely underdeveloped liver. The co injection of TNF-alpha MO and mRNA rescued the liver development. Retinal neurogenesis in TNF-alpha morphants was initiated on time. The retina was fully laminated, while ganglion cells, cones, and rods were well differentiated at 72 hours post-fertilization (hpf). mbp was expressed in Schwann cells in the lateral line nerves and cranial nerves from 3 days post-fertilization (dpf) as well as in oligodendrocytes linearly along the hindbrain bundles and the spinal cord from 4 dpf, which closely resembled its endogenous profile. CONCLUSION: TNF-alpha is not an essential regulator for retinal neurogenesis and optic myelination. PMID- 27366684 TI - Histopathologic effects of a low molecular weight heparin on bone healing in rats: a promising adjuvant in dacryocystorhinostomy. AB - AIM: To investigate the effect of short-term prophylactic dose of a low molecular weight heparin (LMWH) drug on the bone healing process in an animal model simulating the osteotomy obtained in dacryocystorhinostomy. METHODS: Forty male Wistar albino rats were divided into 2 groups. Subcutaneous injections of enoxaparin 1 mg/kg (enoxaparin-treated group) and saline solution (control group) were performed once daily for 4d, beginning on the first preoperative day. The osteotomy was created at the femoral diaphysis in all animals by using a Kirschner wire. Each group was further divided into 2 subgroups depending on the timing of the second operation, 14 or 21d following initial osteotomy. Patent osteotomy area on the second and the third weeks in each group were calculated by using a computer software on digital micrographs. RESULTS: The patent osteotomy areas at the second and the third weeks were significantly larger in the enoxaparin-treated group than those of the control group (P<0.001 for each time period). In the control group, the patent osteotomy area at the third week of healing was significantly smaller than that of the second week (P=0.003), whereas there was no significant difference between these two measurements in the enoxaparin-treated group (P=0.185). CONCLUSION: Short-term administration of enoxaparin resultes in a significant alteration in bone healing at 14 and 21d after injury. LMWHs can be regarded as promising alternative adjuvants in dacryocystorhinostomy after being evaluated with further clinical and animal studies. PMID- 27366685 TI - Long-term outcomes of wedge resection at the limbus for high irregular corneal astigmatism after repaired corneal laceration. AB - AIM: To evaluate the clinical value of wedge resection at corneal limbus in patients with traumatic corneal scarring and high irregular astigmatism. METHODS: Patients with traumatic corneal astigmatism received wedge resection at least 6mo after suture removal from corneal wound. The uncorrected distance visual acuities (UCVA) and best corrected distance visual acuities (BCVA), pre- and post operation astigmatism, spherical equivalent (SE), safety and complications were evaluated. RESULTS: Ten eyes (10 patients) were enrolled in this study. Mean follow-up time after wedge resection was 37.8+/-15.4mo (range, 20-61mo). The mean UCVA improved from +1.07+/-0.55 logMAR to +0.43+/-0.22 logMAR (P=0.000) and the mean BCVA from +0.50+/-0.30 logMAR to +0.15+/-0.17 logMAR (P=0.000). The mean astigmatism power measured by retinoscopy was -2.03+/-2.27 D postoperatively and 2.83+/-4.52 D preoperatively (P=0.310). The mean SE was -0.74+/-1.61 D postoperatively and -0.64+/-1.89 D preoperatively (P=0.601). Two cases developed mild pannus near the sutures. No corneal perforation, infectious keratitis or wound gape occurred. CONCLUSION: Corneal-scleral limbal wedge resection with compression suture is a safe, effective treatment for poor patients with high irregular corneal astigmatism after corneal-scleral penetrating injury. Retinoscopy can prove particularly useful for high irregular corneal astigmatism when other measurements are not amenable. PMID- 27366686 TI - Surgical management of fungal endophthalmitis resulting from fungal keratitis. AB - AIM: To report the fungal organisms, clinical features, surgical treatment strategies, and outcomes of patients with culture-proven exogenous fungal endophthalmitis (EFE) secondary to keratitis, and evaluate the role of surgery in the treatment. METHODS: The clinical records of 27 patients (27 eyes) with culture-proven EFE resulting from fungal keratitis treated at Shandong Eye Institute from January 2007 to January 2015 were retrospectively reviewed. Information about fungal culture results, clinical features, surgical procedures, and final visual acuity was obtained. RESULTS: There were 39 positive culture results from samples of cornea, hypopyon, vitreous and lens capsule, accounting for 56%, 26%, 15% and 2.5%, respectively. Fusarium was identified in 44% (12/27) of the eyes, followed by Aspergillus in 22% (6/27). Posterior segment infection was involved in 78% (21/27) of the patients. The corneal infection was larger than 3 mm *3 mm in 89% (24/27) of the patients, and 22% (6/27) of them had the entire cornea, and even the sclera involved. Three eyes had silicone oil tamponade, and two eyes had retinal detachment. Twenty-two eyes (81.5%) underwent penetrating keratoplasty (PKP), and over half of them (54.5%) were operated within 3d from the onset of antifungal therapy. Fourteen eyes (52%) underwent intracameral antifungal drug injection, and three of them required repeated injections. Fifteen eyes (55.6%) underwent pars plana vitrectomy (PPV). The rate of the eyes undergoing PPV as the initial surgical procedure was 60% (9/15), lower than 77% in PKP. Intravitreal injection was given in 59% of the eyes (16/27), and 75% of them required repeated injections. The final visual acuity was 20/100 or better in 37% of the eyes, and better than counting fingers in 55.6% of the eyes. Five eyes (18.5%) were eviscerated. In the two eyes with concurrent retinal detachment, one achieved retinal reattachment, and the other was eviscerated. In the three eyes with silicone oil tamponade, two eyes received silicone oil removal, and the other one was eviscerated. CONCLUSION: Fusarium and Aspergillus are the dominant pathogens in EFE resulting from keratitis. Aggressive antifungal surgeries including multiple intravitreal injections, PKP and core vitrectomy (especially in the initial surgery) are helpful procedures to improve prognosis of severe EFE secondary to keratitis. PMID- 27366687 TI - Effect of biometric characteristics on biomechanical properties of the cornea in cataract patient. AB - AIM: To determine the impact of biometric characteristics on the biomechanical properties of the human cornea using the ocular response analyzer (ORA) and standard comprehensive ophthalmic examinations before and after standard phacoemulsification. METHODS: This study comprised 54 eyes with cataract with significant lens opacification in stages I or II that underwent phacoemulsification (2.8 mm incision). Corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and corneal-compensated intraocular pressure (IOPcc) were measured by ORA preoperatively and at 1mo postoperatively. Biometric characteristics were derived from corneal topography [TMS-5, anterior equivalent (EQTMS) and cylindric (CYLTMS) power], corneal tomography [Casia, anterior and posterior equivalent (EQaCASIC, EQpCASIA) and cylindric (CYLaCASIA, CYLpCASIA) power], keratometry [IOLMaster, anterior equivalent (EQIOL) and cylindric (CYLIOL) power] and autorefractor [anterior equivalent (EQAR)]. Results from ORA were analyzed and correlated with those from all other examinations taken at the same time point. RESULTS: Preoperatively, CH correlated with EQpCASIA and CYLpCASIA only (P=0.001, P=0.002). Postoperatively, IOPg and IOPcc correlated with all equivalent powers (EQTMS, EQIOL, EQAR, EQaCASIA and EQpCASIA) (P=0.001, P=0.007, P=0.001, P=0.015, P=0.03 for IOPg and P<0.001, P=0.003, P<0.001, P=0.009, P=0.014 for IOPcc). CH correlated postoperatively with EQaCASIA and EQpCASIC only (P=0.021, P=0.022). CONCLUSION: Biometric characteristics may significantly affect biomechanical properties of the cornea in terms of CH, IOPcc and IOPg before, but even more after cataract surgery. PMID- 27366688 TI - Peripheral retinal non-perfusion and treatment response in branch retinal vein occlusion. AB - AIM: To evaluate the association between the size of peripheral retinal non perfusion and the number of intravitreal ranibizumab injections in patients with treatment-naive branch retinal vein occlusion (BRVO) and macular edema. METHODS: A total of 53 patients with treatment-naive BRVO and macular edema were included. Each patient underwent a full ophthalmologic examination including optical coherence tomography (OCT) imaging and ultra wide-field fluorescein angiography (UWFA). Monthly intravitreal ranibizumab injections were applied according to the recommendations of the German Ophthalmological Society. Two independent, masked graders quantified the areas of peripheral retinal non-perfusion. RESULTS: Intravitreal injections improved best-corrected visual acuity (BCVA) significantly from 22.23+/-16.33 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters to 36.23+/-15.19 letters (P<0.001), and mean central subfield thickness significantly reduced from 387+/-115 um to 321+/-115 um (P=0.01). Mean number of intravitreal ranibizumab injections was 3.61+/-1.56. The size of retinal non-perfusion correlated significantly with the number of intravitreal ranibizumab injections (R=0.724, P<0.001). CONCLUSION: Peripheral retinal non perfusion in patients with BRVO associates significantly with intravitreal ranibizumab injections in patients with BRVO and macular edema. PMID- 27366689 TI - High frequency of latent Chlamydia trachomatis infection in patients with rhegmatogenous retinal detachment. AB - AIM: To determine the frequency of detection of ocular and extraocular Chlamydia trachomatis (CT) infection in non-high myopes with rhegmatogenous retinal detachment (RRD). METHODS: This was a single-center, nonrandomized, prospective, case-control study. One hundred and four patients were divided into a study group with RRD (n=63) and a control group with traumatic retinal detachment (n=41). Samples of subretinal fluid (SFR), conjunctival, urethral/cervical swabs, and blood were collected. The frequency of detection of CT infection in SRF samples was determined by polymerase chain reaction (PCR), direct fluorescence assay (DFA) and cell culture, whereas that in conjunctival swabs was determined by PCR and DFA, and those in urethral/cervical swabs and blood were determined by DFA. Yates Chi-square test (with Bonferroni correction) and two-tailed Student's t test were used for statistical analysis. RESULTS: SRF CT infection was detected more frequently in the study group (50.8%-71.4%) than in the control group (9.8% 12.2%) by all the methods used (P<0.01). The frequency of detection of conjunctival CT infection by DFA was higher in the RRD patients compared with the controls (81.0% vs 24.4%, P=0.004). The PCR detected conjunctival CT infection more often in the study group than in the controls (46.0% vs 9.8%, P=0.007). The DFA detected CT in blood specimens almost as frequently as in urogenital specimens, for the RRD patients (61.2% vs 63.5%) and the controls (7.3% vs 9.8%). CONCLUSION: CT infection is detected with high frequency in non-high myopes with RRD. PMID- 27366690 TI - Orbital decompression surgery and horse chestnut seed extract improved superior orbital vein blood flow in patients with thyroid-associated ophthalmopathy. AB - AIM: To evaluate the efficacy and safety of orbital decomposition (OD) surgery in combination with horse chestnut seed extract (HCSE), as compared to OD alone, in patients with thyroid-associated ophthalmopathy (TAO). METHODS: Sixty-two orbits from 62 TAO patients were randomly assigned to OD or OD+HCSE at 1:1 ratio (31 received OD alone, 31 received OD+HCSE). Forty-two orbits from 21 healthy subjects were used as controls. Complete ophthalmic examination and color Doppler flow imaging (CDFI) were performed before surgery and 3mo post-surgery on all 62 orbits from the TAO patients. CDFI were also performed on the 42 control orbits. The effect of OD+HCSE and OD alone on TAO orbits was compared on several endpoints, including superior ophthalmic vein blood flow (SOVBF) parameters, subjective assessment, soft tissue involvement, lid retraction, diplopia, eye movement restriction, degree of exophthalmos, and intraocular pressure. The control orbits were used as reference for the SOVBF parameters. RESULTS: OD surgery with or without HCSE improved SOVBF, symptoms and soft tissue involvement, decreased degree of exophthalmos and intraocular pressure in orbits of TAO patients. The OD+HCSE combination led to significantly better improvement of SOVBF than OD alone. The differences between the reductions of SOVBF in the two groups are 1.26 cm/s in max-volecity and 0.52 cm/s in min-volecity (P<0.0001). CONCLUSION: SOVBF is significantly reduced in the orbits affected with TAO, indicating that congestion may be an important factor contributing to TAO pathogenesis. OD surgery improves the SOVBF, and combination of HCSE medication and OD surgery further improved venous return than OD surgery alone. PMID- 27366691 TI - Comparison axial length measurements from three biometric instruments in high myopia. AB - AIM: To compare the axial lengths (ALs) measured with Lenstar, IOLMaster and A scan contact ultrasound (Ultrasound) in normal and high myopia (HM). METHODS: Eighty-four normal eyes and 49 HM eyes were included. Three consecutive measurements were performed on each eye in the following order: Lenstar, IOLMaster, and Ultrasound. The repeatabilities of the AL measurements for each instrument were assessed by calculating the pooled coefficients of variation (CVs) of 18 eyes in each group. Comparisons between the HM and normal groups were made with independent sample t-tests. The inter-device agreements were evaluated with Bland-Altman analyses and paired two-tailed t-tests. RESULTS: For normal group, the CVs of the AL measurements taken with the Lenstar, IOLMaster and Ultrasound were 0.001%, 0.01% and 0.14%, respectively. The corresponding CVs for the HM group were 0.005%, 0.02% and 0.15%, respectively. There was significant difference between the Lenstar and the IOLMaster in normal group (P=0.031) but not in HM group (P=0.100). In the two groups, the Lenstar and the IOLMaster produced higher values than did the Ultrasound (all P<0.001). All three instruments exhibited good agreement in terms of AL values. For the intraocular lens (IOL) power calculation using SRK II formula, the Lenstar and the IOLMaster showed 0.5 D higher than Ultrasound in both groups (all P<0.001). No significant difference existed between the Lenstar and the IOLMaster for the IOL power calculation in both normal (P=0.474) and HM group (P=0.103). CONCLUSION: The three devices exhibited excellent intra-visit repeatabilities in the AL measurements. The AL and IOL power difference between partial coherence interferometry and ultrasound instruments should be noticed. PMID- 27366692 TI - Visual and ocular effects from the use of flat-panel displays. AB - AIM: To evaluate the prevalence of eye symptoms in a non-presbyopic population of video display unit (VDU) users with flat-panel displays. METHODS: One hundred and sixteen VDU users with flat-panel display from an urban population participated in the study; their ages ranging from 20 to 34y. There were 60 females and 56 males. An eye examination to rule out the presence of significant uncorrected refractive errors, general binocular dysfunctions and eye conditions was carried out. In order to determine and quantify the type and nature of eye symptoms, participants were asked to answer written questionnaire and the results were grouped by gender, age and number of hours a day spent using a VDU. RESULTS: Seventy-two percent of participants reported eye symptoms related to VDU use. Eye symptoms from moderate-to-severe were found in 23% of participants. The main symptom was moderate-to-severe tired eyes (14%); followed by sensitivity to bright lights (12%), blurred vision at far distances (10%), eyestrain or dry eye or irritated or burning eyes (9%), difficulty in refocusing from one distance to another or headache (8%) and blurred vision at near or intermediate distances (<4%). Eye symptoms were greater among females (P=0.005) and increased with VDU use, markedly above 6h spent using a VDU in a typical day (P=0.01). CONCLUSION: Significant eye symptoms relate to VDU use often occur and should not be underestimated. The increasing use of electronic devices with flat-panel display should prompt users to take appropriate measures to prevent or to relieve the eye symptoms arising from their use. PMID- 27366693 TI - Clinical risk factors for the development of consecutive exotropia: a comparative clinical study. AB - AIM: To compare a group of patients with consecutive exotropia with patients who had <=10 prism diopters (PD) esotropia or no deviation postoperatively in terms of probable clinical risk factors for the development of consecutive exotropia. METHODS: The study recruited fourteen patients who developed consecutive exodeviation during follow-up period after the correction of esotropia who were categorized as group 1 and thirty-one patients who had still <=10 PD esotropia or no deviation at the final visit that were considered as group 2. Clinical risk factors leading the development of consecutive deviation were analyzed as the main outcome measures. RESULTS: The mean age of patients was 4.57+/-3.11y in group 1 and 5.10+/-3.52y in group 2 (P=0.634). There was no significant difference of preoperative near and distant deviations among two groups (P=0.835, 0.928 respectively). The mean amount of medial rectus recession and lateral rectus resection was similar in both groups (P=0.412, 0.648 respectively). Convergence insufficiency and neurological diseases were more frequent in group 1 (P=0.007, 0.045). Accompanying neurological disease was found to be as a significant factor increasing the risk of the development of consecutive exotropia significantly [odds ratios (OR): 5.75 (1.04-31.93)]. CONCLUSION: Accompanying neurological disease appears to be a significant clinical risk factor for the development of consecutive exodeviation during postoperative follow-up after the correction of esotropia. However, larger studies are needed in order to interpret the results to the clinical practice and to ascertain other concurrent risk factors. PMID- 27366694 TI - An evaluation of intraoperative and postoperative outcomes of torsional mode versus longitudinal ultrasound mode phacoemulsification: a Meta-analysis. AB - AIM: To evaluate and compare the intraoperative parameters and postoperative outcomes of torsional mode and longitudinal mode of phacoemulsification. METHODS: Pertinent studies were identified by a computerized MEDLINE search from January 2002 to September 2013. The Meta-analysis is composed of two parts. In the first part the intraoperative parameters were considered: ultrasound time (UST) and cumulative dissipated energy (CDE). The intraoperative values were also distinctly considered for two categories (moderate and hard cataract group) depending on the nuclear opacity grade. In the second part of the study the postoperative outcomes as the best corrected visual acuity (BCVA) and the endothelial cell loss (ECL) were taken in consideration. RESULTS: The UST and CDE values proved statistically significant in support of torsional mode for both moderate and hard cataract group. The analysis of BCVA did not present statistically significant difference between the two surgical modalities. The ECL count was statistically significant in support of torsional mode (P<0.001). CONCLUSION: The Meta-analysis shows the superiority of the torsional mode for intraoperative parameters (UST, CDE) and postoperative ECL outcomes. PMID- 27366695 TI - Radial optic neurotomy in treating central retinal vein occlusion: a Meta analysis. AB - AIM: To assess the feasibility of radial optic neurotomy (RON) in central retinal vein occlusion (CRVO) treatment with a Meta-analysis. METHODS: Electronic databases were searched for comprehensive articles that compared efficacy of RON with that of other treatments in CRVO. Study quality was assessed and risk ratio (RR) and 95% confidence interval (CI) with fix- or random-effects model were calculated according to the heterogeneity. RESULTS: A total of 200 eyes from 5 studies were included. The results indicated that no significant differences were found between groups with and without RON in improvement of visual acuity (VA) at 6mo follow-up (pooled RR 0.51, 95%CI 0.22 to 1.18, P=0.117) while improvement of VA showed significantly favourable in patients receiving RON treatment at 12mo follow-up (pooled RR 2.27, 95%CI 1.31 to 3.95, P=0.004). For complications, RON treatment was more effective in reducing neovascular glaucoma (pooled RR 0.45, 95%CI 0.21 to 0.97, P=0.042) but was comparable in retinal detachment (pooled RR 2.41, 95%CI 0.51 to 11.39, P=0.267) and vitreous hemorrhage (pooled RR 0.91, 95%CI 0.33 to 2.46, P=0.847). CONCLUSION: Compared with some certain treatment modalities, RON might offer better VA at 12mo and decrease the rate of neovascular glaucoma without changing the rate of retinal detachment and vitreous hemorrhage. Further studies are required considering the limitation of the research. PMID- 27366696 TI - Characteristics of corneal dystrophies: a review from clinical, histological and genetic perspectives. AB - Corneal dystrophy is a common type of hereditary corneal diseases. It includes many types, which have varied pathology, histology and clinical manifestations. Recently, the examination techniques of ophthalmology and gene sequencing advance greatly, which do benefit to our understanding of these diseases. However, many aspects remain still unknown. And due to the poor knowledge of these diseases, the results of the treatments are not satisfoctory. The purpose of this review was to summarize the clinical, histological and genetic characteristics of different types of corneal dystrophies. PMID- 27366697 TI - The transcorneal electrical stimulation as a novel therapeutic strategy against retinal and optic neuropathy: a review of experimental and clinical trials. AB - Transcorneal electrical stimulation (TES) is a novel therapeutic approach to activate the retina and related downstream structures. TES has multiple advantages over traditional treatments, such as being minimally invasive and readily applicable in a routine manner. Series of animal experiments have shown that TES protects the retinal neuron from traumatic or genetic induced degeneration. These laboratory evidences support its utilization in ophthalmological therapies against various retinal and optical diseases including retinitis pigmentosa (RP), traumatic optic neuropathy, anterior ischemic optic neuropathy (AION), and retinal artery occlusions (RAOs). Several pioneering explorations sought to clarify the functional mechanism underlying the neuroprotective effects of TES. It seems that the neuroprotective effects should not be attributed to a solitary pathway, on the contrary, multiple mechanisms might contribute collectively to maintain cellular homeostasis and promote cell survival in the retina. More precise evaluations via functional and morphological techniques would determine the exact mechanism underlying the remarkable neuroprotective effect of TES. Further studies to determine the optimal parameters and the long-term stability of TES are crucial to justify the clinical significance and to establish TES as a popularized therapeutic modality against retinal and optic neuropathy. PMID- 27366698 TI - Ophthalmology simulation for undergraduate and postgraduate clinical education. AB - This is a review education paper on the current ophthalmology simulators utilized worldwide for undergraduate and postgraduate training. At present, various simulators such as the EYE Exam Simulator (Kyoto Kagaku Co. Ltd., Kyoto, Japan), Eyesi direct ophthalmoscope simulator (VRmagic, GmbH, Mannheim, Germany), Eyesi indirect ophthalmoscope simulator (VRmagic, GmbH, Mannheim, Germany) and Eyesi cataract simulators (VRmagic, GmbH, Mannheim, Germany). These simulators are thought to be able to reduce the initial learning curve for the ophthalmology training but further research will need to be conducted to assess the effectiveness of the simulation-assisted Ophthalmology training. Future research will be of great value to assess the medical students and residents' responses and performance regarding the usefulness of the individual eye simulator. PMID- 27366699 TI - Intraocular lens exchange-removing the optic intact. AB - Current practice for intraocular lens (IOL) exchange is to cut the optic of the posterior chamber intraocular lens (PCIOL) prior to removing it. Great care must be taken during this maneuver to avoid a posterior capsular tear. Removing the haptics from the fibrosed capsule can also be hazardous, as it may result in zonular stress and dehiscence. A technique is described for performing foldable (one-piece acrylic) IOL removal without cutting the optic. Careful visco dissection of the haptics with a low viscosity ophthalmic viscosurgical device (OVD) in the fibrosed peripheral capsular tunnel avoids zonular or capsular stress. Internal wound enlargement permits foldable IOL removal in one piece, whilst preserving a self-sealing sutureless corneal wound. This technique may enhance the safety and efficacy of foldable IOL exchange. PMID- 27366700 TI - The short-needle intravitreal injection technique. PMID- 27366701 TI - Overexpression of carbonic anhydrase 1 in pterygium. PMID- 27366702 TI - Anterior segment optical coherence tomography for identifying muscle status in strabismus surgery. PMID- 27366703 TI - Comment on concurrent removal of intravitreal lens fragments after phacoemulsification with pars plana vitrectomy prevents development of retinal detachment. PMID- 27366704 TI - Glycemic control in Intensive Care Unit. PMID- 27366706 TI - Metabolic state of the nation: Results of the national family health survey-4. PMID- 27366705 TI - Triglyceride and cardiovascular risk: A critical appraisal. PMID- 27366707 TI - Novel multiple endocrine neoplasia type 1 variations in patients with sporadic primary hyperparathyroidism. AB - BACKGROUND AND OBJECTIVES: Primary hyperparathyroidism (PHPT) can occur either as a sporadic case or in association with syndromes such as multiple endocrine neoplasia. Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant disease resulting from mutations in MEN1 gene encoding a 621 amino acid long tumor suppressor protein "menin." We report here the results of MEN1 screening in 31 patients diagnosed with sporadic PHPT. MATERIALS AND METHODS: Diagnosis of sporadic PHPT was made when blood urea and serum creatinine were normal, serum parathyroid hormone was high, and parathyroid enlargement could be localized on ultrasound and/or parathyroid scan. A total of 31 patients and 50 healthy volunteers were recruited for molecular analysis after taking informed consent. RESULTS: Major symptoms at presentation were bone pain, fatigue, muscle weakness, and renal stones. Molecular genetic analysis revealed the presence of two novel intronic variations, c. 913-79T>A and c. 784-129T>A which by human splicing finder are predicted to cause potential alteration of splicing by either activating an intronic cryptic acceptor site or converting a conserved exonic splicing silencer sequence to an exonic splicing enhancer site. Apart from these, two reported polymorphisms rs144677807 and rs669976 were seen only in patients and none of the controls. Other reported polymorphisms rs2071313 and rs654440 were identified both in controls and patients. CONCLUSIONS: This is the first study of MEN1 gene screening in sporadic PHPT in India reporting on the clinical and genetic findings, wherein two novel intronic variations c. 913-79T>A and c. 784-129T>A were identified showing their possible role in disease causation. PMID- 27366708 TI - Prevalence of colonic polyp and its predictors in patients with acromegaly. AB - BACKGROUND: There are conflicting data regarding the prevalence of colorectal polyp in patients with acromegaly. SUBJECTS AND METHODS: Consecutive forty-seven acromegalic patients (21 men, 26 women), with a mean age of (40 +/- 12 years) attending endocrinology outpatient department underwent full colonoscopy. All the patients underwent clinical and biochemical evaluation (glucose suppressed growth hormone (GH), Insulin-like growth factor-1 [IGF-1], fasting insulin, and glucose). The control group (n = 120) for colonoscopy was adult subjects undergoing evaluation for symptoms of irritable bowel syndrome. Clinical and biochemical parameters in acromegalic patients with colonic polyp were compared to those without a polyp. RESULTS: Patients with acromegaly had significantly higher prevalence of colonic polyp as compared to control subjects (10.6% vs. 0.8%). None of the patients with polyp had skin tags. There was no significant difference between subjects with and without colonic polyp in duration of illness, basal, and glucose-suppressed GH and most recent IGF-1. Fasting blood sugar was significantly higher (P < 0.05) in adenoma group after adjusting for age, body mass index (BMI), and insulin levels. Patients in adenoma group showed a trend toward male gender and younger age as compared to those without adenoma. CONCLUSIONS: Subjects with acromegaly as compared to control have a higher prevalence of colonic polyps. There was no association of polyps seen with age, BMI, skin tags, homeostasis model assessment of insulin resistance index, duration of disease, and basal and glucose-suppressed GH and IGF-1 levels. There were no specific predictive factors detected. Screening full colonoscopy is recommended in all cases with acromegaly. PMID- 27366709 TI - Clinical safety of insulin detemir in patients with Type 2 diabetes in the Gulf countries: The multicenter, noninterventional, open-label LevSafe study. AB - AIM: To evaluate the safety profile of insulin detemir (IDet) in people with Type 2 diabetes mellitus (T2DM) in the Gulf countries in the 32-week, noninterventional LevSafe study. METHODS: People with T2DM whose physicians had opted to start IDet therapy were included in the study. Safety parameters, including serious adverse drug reactions (SADRs) and hypoglycemia, and changes in body weight and glycemic control were evaluated at baseline, week 16 and week 32. RESULTS: A total of 686 patients were exposed to IDet therapy with a mean (+/ standard deviation) age, body mass index, and diabetes duration of 51.3 +/- 11.0 years, 31.3 +/- 5.5 kg/m(2), and 10.2 +/- 6.1 years, respectively. The mean total daily dose of IDet was 32.0 +/- 32.8 U at baseline and 44.7 +/- 60.7 U at week 32. No SADRs were reported during the study. Total hypoglycemia decreased from 435 events at baseline to 204 events at week 32 (mean change analyzed by Wilcoxon signed rank test: -0.34; P = 0.0115), and no major hypoglycemia was reported at week 32. Over the 32-week treatment period, the mean body weight decreased from 85.7 +/- 15.2 kg to 85.4 +/- 14.5 kg (P = 0.0203), glycated hemoglobin A1c from 9.9 +/- 1.67% to 7.7 +/- 1.36% (P < 0.0001), and fasting plasma glucose from 11.9 +/- 3.27 mmol/L to 7.4 +/- 1.85 mmol/L (P < 0.0001). CONCLUSION: IDet therapy was well-tolerated and was associated with a decreased number of hypoglycemic events and improved glycemic control after 32 weeks in patients with T2DM in the Gulf countries. PMID- 27366711 TI - Prevalence and severity of disordered mineral metabolism in patients with chronic kidney disease: A study from a tertiary care hospital in India. AB - BACKGROUND: Disordered mineral metabolism is common complications of chronic kidney disease (CKD). However, there are limited data on the pattern of these disturbances in Indian CKD population. MATERIALS AND METHODS: This was a prospective observational study of CKD-mineral and bone disorder (CKD-MBD) over a period of 3 years. The biochemical markers of CKD-MBD, namely, calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone (iPTH), and 25 hydoxyvitamin Vitamin D3 (25OHD), were measured in newly diagnosed CKD Stage 3-5 and prevalent CKD Stage 5D adult patients. RESULTS: A total of 462 patients of CKD Stage 3-5D were studied. The frequency of various biochemical abnormalities was hypocalcemia (23.8%), hypercalcemia (5.4%), hypophosphatemia (2.8%), hyperphosphatemia (55.4%), raised alkaline phosphatase (56.9%), secondary hyperparathyroidism (82.7%), and hypoparathyroidism (1.5%). 25OHD was done in 335 (72.5%) patients and 90.4% were found to have Vitamin D deficiency. About 70.6% of the patients had iPTH levels were above kidney disease outcomes quality initiative (KDOQI) target range. Nondiabetic CKD as compared to diabetic CKD had a higher alkaline phosphatase (P = 0.016), a higher iPTH (P = 0.001) a higher proportion of patients with iPTH above KDOQI target range (P = 0.09), and an elevated alkaline phosphatase (P = 0.004). The 25OHD levels were suggestive of severe Vitamin D deficiency in 33.7%, Vitamin D deficiency in 45.4%, and Vitamin D insufficiency in 11.3% patients. There was a significant positive correlation between iPTH with alkaline phosphatase (r = 0.572, P = 0.001), creatinine (r = 0.424, P = 0.001), and phosphorus (r = 0.241, P = 0.001) and a significant negative correlation with hemoglobin (r = -0.325, 0.001), age (r = -0.169, P = 0.002), and 25OHD (r = -0.126, P = 0.021). On multivariate logistic regression analysis, an elevated alkaline phosphatase was a significant predictor of hyperparathyroidism (odds ratio 9.7, 95% confidence interval 4.9-19.2, P = 0.001). CONCLUSIONS: There was a high prevalence of CKD-MBD in Indian CKD patients. CKD-MBD is more common and more severe and has an early onset as compared to the western populations. PMID- 27366710 TI - Endocrine profile of beta-thalassemia major patients followed from childhood to advanced adulthood in a tertiary care center. AB - AIM: Chronic iron overload resulting from frequent transfusions, poor compliance to efficient chelation therapy and chronic liver disease is basically responsible for the most severe complications of thalassemia major (TM). Before conventional treatment, TM was entirely childhood disease with a very short survival. Today, survival improved to 40-50 years and becomes a prevalent disease of adulthood and in the near future it will be one of senility. Furthermore, clinical phenotype of TM is changing with age and appearance of severe complications from the heart and endocrine glands that require special health care from well-informed specialists. OBJECTIVES: The aims of our study were to: (1) Imprint the clinical profile of long-lived TM patients; (2) evaluate retrospectively the cumulative incidence of endocrine diseases; (3) identify potential risk factors; and (4) orient the physicians in the modified clinical phenotype and the relative patients' health needs. DESIGN: A retrospective cross-sectional study followed from childhood to adulthood by the same physician in a tertiary thalassemia clinic. PARTICIPANTS: Forty-three long-lived TM patients (mean age: 50.3 +/- 10.8 years; range: 45.8 59.5 years; 23 females) were studied. PATIENTS AND METHODS: An extensive medical history, with detailed clinical and laboratory data, endocrine complications, and current treatments, was obtained. RESULTS: The data indicate that 88.4% of adult TM patients suffered from at least one endocrine complication. The majority of patients developed endocrine complications in the second decade of life when serum ferritin level was very high (12/23 TM female and 8/20 TM male patients, the serum ferritin levels at the diagnosis were above 5.000 ng/ml). CONCLUSIONS: These data underline that endocrine and bone complications in adult TM patients are highly prevalent and necessitate close monitoring, treatment, and follow-up. Physicians' strategies to optimize chelation therapy include identifying patients who are at risk for developing organ damage, developing chelation plans, promoting compliance, and educating patients. Several clinical aspects remain to be elucidated such as growth and impairment of glucose tolerance in relation to hepatitis C virus infection. Furthermore, affordable worldwide-established long term treatment protocols for hypogonadism and osteoporosis are needed. PMID- 27366713 TI - Emphysematous pyelonephritis: A 10-year experience with 26 cases. AB - BACKGROUND: Emphysematous pyelonephritis (EPN) is a necrotizing infection which results in gas within the renal parenchyma, collecting system, or perinephric tissue. A majority of cases occur in patients with diabetes mellitus (DM). In EPN, early aggressive medical treatment may avoid nephrectomy. AIMS: The aim of this study was to analyze the characteristics of patients with EPN with respect to patient demographics, clinical presentation, diagnostic investigations, microbiological findings, treatment modality and outcome, and the influence of prognostic factors on the outcome. MATERIALS AND METHODS: We reviewed the hospital records of 26 patients with EPN for clinical, laboratory, radiological, and microbiological findings, treatments given, and outcome. The severity of EPN was graded as per the Huang classification. We applied the reported prognostic factors to our patients to find out whether these factors correlated with failure of conservative treatment. RESULTS: All the study subjects had DM and all but two of them were females. The majority of our patients (61.5%) had extensive EPN (class 3 or 4) and majority (76.9%) had two or more bad prognostic factors. Escherichia coli was the most common causative organism involved in 50% of our cases. Twenty-three (88.5%) of our patients responded to conservative treatment, two required nephrectomy, and one expired on conservative treatment. CONCLUSIONS: In this series of patients with EPN, all had DM, nearly all were women, and E. coli was the most frequently isolated pathogen. Nearly a third of our patients had bilateral disease. Despite the presence of two or more bad prognostic factors and extensive EPN (class 3 or 4) in a majority of our patients, conservative treatment afforded a striking success rate of 88.5%. We recommend early aggressive medical treatment and suggest that nephrectomy should be considered only if patients deteriorate or do not improve on conservative treatment. PMID- 27366712 TI - Prevalence of anxiety and depressive symptoms among patients with hypothyroidism. AB - CONTEXT: The association between depression and thyroid function is well known. Both conditions express many similar symptoms, thus making the diagnosis and treatment difficult. AIMS: To find the prevalence of anxiety and depressive symptoms among patients with hypothyroid. SETTINGS AND DESIGN: Cross-sectional study. MATERIALS AND METHODOLOGY: A total of 100 patients diagnosed as hypothyroidism were evaluated using Hamilton depression rating scale (HDRS) and Hamilton scale for anxiety (HAM-A). STATISTICAL ANALYSIS USED: The data were analyzed using the SPSS for Windows version 17.0 software. The quantitative data were expressed in number and percentage. The results obtained were compared using the Chi-square test. RESULTS: Females constituted 70% of the sample. A total of 60% reported some degree of depression based on HDRS (males - 56.63% and females 64.29%) whereas about 63% out of the total patients screened showed some degree of anxiety (males -56.66% and females - 65.72%) based on HAM-A. The most common depressive symptom among the males was depressed mood (73.33%) and among females was gastrointestinal somatic symptoms (68.54%). The most common anxiety symptom among the males was depressed mood (70.0%) and among females was anxious mood (92.85%). CONCLUSIONS: Psychiatric symptoms/disorders are common in patients with thyroid dysfunction. PMID- 27366714 TI - Glycemic control and pregnancy outcomes in patients with diabetes in pregnancy: A retrospective study. AB - CONTEXT: Diabetes in pregnancy (DIP) is either pregestational or gestational. AIMS: To determine the relationship between glycemic control and pregnancy outcomes in a cohort of DIP patients. SETTINGS AND DESIGN: In this 12-month retrospective study, a total of 325 Saudi women with DIP who attended the outpatient clinics at a tertiary center Riyadh, Saudi Arabia, were included. SUBJECTS AND METHODS: The patients were divided into two groups, those with glycated hemoglobin (HbA1c) <=6.5% (48 mmol/mol) and those with glycated hemoglobin (HbA1c) above 6.5%. The two groups were compared for differences in maternal and fetal outcomes. STATISTICAL ANALYSIS USED: Independent Student's t test and analysis of variance were performed for comparison of continuous variables and Chi-square test for frequencies. Odds ratio and 95% confidence intervals were calculated using logistic regression. RESULTS: Patients with higher HbA1c were older (P = 0.0077), had significantly higher blood pressure, proteinuria (P < 0.0001), and were multiparous (P = 0.0269). They had significantly shorter gestational periods (P = 0.0002), more preterm labor (P < 0.0001), more perineal tears (P = 0.0406), more miscarriages (P < 0.0001), and more operative deliveries (P < 0.0001). Their babies were significantly of greater weight, had more Neonatal Intensive Care Unit (NICU) admissions, hypoglycemia, and macrosomia. CONCLUSIONS: Poor glycemic control during pregnancy is associated with adverse maternal and fetal outcomes (shortened gestational period, greater risk of miscarriage, increased likelihood of operative delivery, hypoglycemia, macrosomia, and increased NICU admission). Especially at risk are those with preexisting diabetes, who would benefit from earlier diabetes consultation and tighter glycemic control before conception. PMID- 27366715 TI - Comparison of maternal and fetal outcomes among Asian Indian pregnant women with or without gestational diabetes mellitus: A situational analysis study (WINGS-3). AB - AIM: To compare the existing maternal and fetal outcomes in Asian Indian women with or without gestational diabetes mellitus (GDM) before the development of the Women in India with GDM Strategy (WINGS) GDM model of care (MOC). MATERIALS AND METHODS: Records of pregnant women were extracted retrospectively from three maternity centers in Chennai. GDM was diagnosed using the International Association for Pregnancy Study Groups criteria or the Carpenter and Coustan criteria. Demographic details, obstetric history, antenatal follow-up, treatment for GDM, and outcomes of delivery were collected from the electronic medical records. RESULTS: Of the 3642 records analyzed, 799 (21.9%) had GDM, of whom 456 (57.1%) were treated with insulin and medical nutrition therapy (MNT), 339 (42.4%) with MNT alone, and 4 (0.5%) with metformin. Women with GDM were older than those without (28.5 +/- 4.5 vs. 27.1 +/- 4.5 years; P < 0.001) and had higher mean body mass index at first booking (26.4 +/- 5.2 kg/m(2) vs. 25.2 +/- 5.1 kg/m(2); P < 0.001). Rates of cesarean section (26.2% vs. 18.7%; P < 0.001), preeclampsia (1.8% vs. 0.8%; P = 0.04), and macrosomia (13.9% vs. 10.8%; P = 0.02) were significantly higher among women with GDM. In women with GDM treated with insulin and MNT, emergency cesarean section (16.2% vs. 36.6%; P < 0.0001), preeclampsia (0.7% vs. 3.2%; P = 0.015), and macrosomia (9.9% vs. 18.6%; P = 0.0006) were significantly lesser compared to those treated with MNT alone. CONCLUSION: Pregnancy outcomes were in general worse in GDM women. Treatment with insulin was associated with a significantly lower risk of complications. However, in countries with limited access to insulin and other medicines may lead to poor follow-up and management of GDM. Data from this retrospective study will form the basis for the development of the WINGS GDM MOC, which will address these gaps in GDM care in low-resource settings. PMID- 27366716 TI - Premature birth and insulin resistance in infancy: A prospective cohort study. AB - OBJECTIVE: This study was done to determine the role of prematurity and other variables to predict insulin sensitivity in infancy. SUBJECTS AND METHODS: In this prospective study, 36 preterm appropriate for gestational age (AGA), 11 preterm small for gestational age (SGA), and 17 term SGA included as study cohort and 36 term AGA as control cohort. Detailed anthropometry assessment was performed at birth, 3, 6, and 9 months and at 9 months, fasting plasma glucose and serum insulin was done. Insulin resistance was determined by using homeostasis model assessment version 2. RESULTS: It is found that preterm AGA (mean difference 0.617, 95% confidence interval [CI]; 0.43-0.80, P = 0.0001), preterm SGA (mean difference 0.764, 95% CI; 0.44-1.09, P = 0.0001), and term AGA (mean difference 0.725, 95% CI; 0.49-0.96, P = 0.0001) group had significantly higher insulin resistance than control. There was no significant difference in between preterm SGA and preterm AGA (mean difference 0.147 95% CI; -0.13-0.42, P = 0.927). In multiple regression models, SGA status (beta =0.505) was more significant predictor of insulin resistance index than gestational age (beta = 0.481), weight-for-length (beta =0.315), and ponderal index (beta = -0.194). CONCLUSION: Preterm birth is a risk factor for the future development of insulin resistance which may develop as early as infancy. PMID- 27366717 TI - Impact of insulin pump on quality of life of diabetic patients. AB - AIM: Diabetes is an emerging health problem, both in developing and developed countries and has an enormous economic and social impact. The objective of our study was to find the impact of insulin pump on the quality of life of patients with type 2 diabetes (T2D) and compare it to the quality of life of patients with T2D using an insulin pen. SUBJECTS AND METHODS: This is a case-control study which was conducted among patients with T2D presenting between November 2014 and November 2015. A total of 83 patients with T2D, using insulin pump were enrolled in the study as cases and 322 patients with T2D not using insulin pump but using insulin pens were enrolled as controls. Short form-36 quality of life questionnaire was used for data collection. RESULTS: Mean age of patients using insulin pump was 52.49 +/- 9.28 while the mean age of patients not using insulin pump was 54.72 +/- 16.87. Mean score of all domains in the questionnaire was found to be higher in patients using insulin pump as compared to patients not using insulin pumps (P < 0.05). In 81.1% of the patients, the insulin pump decreased the frequency of hypoglycemic episodes. CONCLUSION: Insulin pump has significantly improved the quality of life of patients in terms of better self esteem, decreased stress, and better mood. It has resulted in improved physical health, meal time flexibility, and ease of travel. It allows patient to have more active participation in social and recreational activities improving their personal and family life. PMID- 27366718 TI - Is intraoperative parathyroid hormone monitoring necessary in symptomatic primary hyperparathyroidism with concordant imaging? AB - INTRODUCTION: Symptomatic primary hyperparathyroidism (PHPT) is still seen frequently in referral centers all over India. These patients require parathyroidectomy and this study aimed to assess the roll of intraoperative parathyroid hormone (PTH) assay when concordant results of two localization studies were available. STUDY DESIGN: We analyzed the case records of patients who underwent parathyroidectomy for PHPT from January 2005 to June 2015. RESULTS: Of 143 patients included in the study, technetium 99m methoxyisobutylisonitrate dual phase scintigraphy showed true positive images in 93.7% and high definition ultrasonography in 84.6% of patients. Concordance in localization studies was observed in 121 (84.6%) patients, successful parathyroidectomy was done in 117 (96.7%) patients with concordant localization studies. Intraoperative PTH monitoring showed 97.84% sensitivity and 75% specificity and predicted failure in 2 patients with concordant imaging. However, re-exploration was not successful in these patients. CONCLUSION: When concordant result is available between parathyroid scintigraphy and anatomical imaging surgical cure rate is high in trained hands. Re-exploration is unlikely to be successful since these patients require higher imaging. PMID- 27366719 TI - A community-based case-control study to investigate the role of iron deficiency in the persistence of goiter. AB - OBJECTIVES: To find out the magnitude of iron deficiency anemia in the age group of 6-12 years and investigate the role of iron deficiency as a possible contributor to endemic goiter in school children in Ambala. MATERIALS AND METHODS: The present study was conducted as a subset of a cross-sectional study among 2700 children from 6 to 12 years of age to find out the prevalence of goiter. All the subjects who were found to be suffering from goiter in the cross sectional study were enrolled in the case-control study as cases and were compared with age- and sex-matched controls (children without goiter) from the same cohort. The study was conducted from February 2011 to January 2012. RESULTS: Out of total, goiter was observed in 12.6% of the subjects. Urinary iodine excretion was found to be <100 MUg/L in 57 (10.5%) children. Mean hemoglobin (Hb) level of the study population was 11.9 g/dL. It was noted that 71% of the goitrous children had anemia (Hb <12 g/dL) as compared to 63.7% of the control group. Serum ferritin (SF) was <15 ng/mL in 70% of the children. The mean +/- standard deviation of SF in the goitrous and nongoitrous children was 19.65 +/- 32.51 MUg/L and 27.55 +/- 21.07 MUg/L, respectively (P = 0.012). CONCLUSION: The findings in the study suggest that iron deficiency anemia in children is contributing toward the persistence of goiter in the postiodization phase. PMID- 27366720 TI - Gut Microbiota in Type 2 Diabetes Individuals and Correlation with Monocyte Chemoattractant Protein1 and Interferon Gamma from Patients Attending a Tertiary Care Centre in Chennai, India. AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) and obesity are associated with changes in gut microbiota and characterized by chronic low-grade inflammation. Monocyte chemoattractant protein-1 (MCP-1) and interferon gamma (IFNgamma) are proinflammatory cytokines which play an important role in the development of T2DM. We undertook this study to analyze the gut microbiota of T2DM and nondiabetic subjects and to determine the profile of MCP 1 and IFNgamma in the same subjects attending a tertiary care center in Chennai, Tamil Nadu, India. METHODS: The study included 30 subjects with clinical details. Stool and blood samples were collected from all the subjects. DNA was extracted from fecal samples and polymerase chain reaction was done using fusion primers. Metagenomic analysis was performed using ion torrent sequencing. The reads obtained were in FASTA format and reported as operational taxonomic units. Human MCP 1 and IFNgamma enzyme linked immunosorbent assay (ELISA) were performed for 23 serum samples. RESULTS: The study consisted of 30 subjects; 17 were T2DM and 13 were nondiabetics. The gut microbiota among T2DM consisted predominantly of Gram negative bacteria; Escherichia and Prevotella, when compared with the nondiabetic group with predominantly Gram positive organisms suchas Faecalibacterium, Eubacterium, and Bifidobacterium. The mean MCP-1 values in the diabetic group were 232.8 pg/ml and in the nondiabetic group 170.84 pg/ml. IFNgamma (mean 385.5 pg/ml) was raised in glycated hemoglobin (HbA1c) group of 6.5-7.5% which was statistically significant. Association of Escherichia with T2DM and association of Bifidobacteria in the nondiabetics were also statistically significant. CONCLUSION: Escherichia counts were elevated in T2DM with HbA1c of 6.5-8.5% which was statistically significant suggesting that lipopolysaccharides present in the cell wall of Gram-negative bacteria may be responsible for low-grade inflammation as evidenced by elevated MCP-1 and IFNgamma levels in T2DM with the same HbA1c levels. PMID- 27366721 TI - Growth status of small for gestational age Indian children from two socioeconomic strata. AB - AIMS: To assess growth and factors associated with growth in children born small for gestational age (SGA) from two socioeconomic strata in comparison to age- and sex-matched healthy controls. METHODS: Retrospective study conducted at two hospitals in Pune, 0.5-5 years, 618 children: 189-SGA from upper socioeconomic strata (USS), 217-SGA from lower socioeconomic strata (LSS), and 212 appropriate for gestational age healthy controls were randomly selected. Birth and maternal history, socioeconomic status, length/height, and weight of children were recorded. Anthropometric data were converted to Z scores (height for age Z-score [HAZ], weight for age Z-score [WAZ]) using WHO AnthroPlus software. RESULTS: The HAZ and WAZ of the SGA group were significantly lower as compared to the controls and that of the LSS SGAs were lower than USS SGAs (P < 0.05). Thirty two percent children were stunted (HAZ <-2.0) in USS and 49% in LSS (P < 0.05). Twenty nine percent children in the USS SGA group were stunted at 2 years and 17% at 5 years. In the LSS SGA group, 54% children were stunted at 2 years and 46% at 5 years. Generalized linear model revealed normal vaginal delivery (beta = 0.625) and mother's age (beta =0.072) were positively associated and high SES (beta = 0.830), absence of major illness (beta = -1.01), higher birth weight (beta = 1.34) were negatively associated for risk of stunting (P < 0.05). CONCLUSION: Children born SGA showed poor growth as compared to controls. Special attention to growth is necessary in children from LSS, very low birth weight babies, and those with major illnesses during early years of life. PMID- 27366722 TI - Gender identity and gender of rearing in 46 XY disorders of sexual development. AB - BACKGROUND: Disorders of sexual development (DSD) may pose a challenge to live as a fully-functioning male or female. In this study, we prospectively assessed eleven 46 XY DSD patients who were being treated at our center over the last 8 months for gender dysphoria. MATERIALS AND METHODS: To determine gender dysphoria, age-appropriate gender identity (GI) questionnaires were used. For patients, 12 years and below, parent report GI questionnaire for children was used and for those above 12 years of age, GI/gender dysphoria questionnaire for adolescents and adults was administered. RESULTS: Of 11 patients with 46 XY DSD, three were diagnosed with 5 alpha reductase deficiency (5aRD), two with partial gonadal dysgenesis, three with partial androgen insensitivity syndrome, one each with ovotesticular, complete gonadal dysgenesis, and complete androgen insensitivity. Gender assigned at birth was female in eight and male in three patients. Among the eight reared as female, gender had been reassigned as male in three patients well before the present study was conducted. None of the eleven patients had gender dysphoria at the time of this study. CONCLUSION: Early gender of rearing was seen to be a critical indicator of present GI in our patients except in cases of 5aRD. PMID- 27366723 TI - Pragmatic use of insulin degludec/insulin aspart co-formulation: A multinational consensus statement. AB - Insulin degludec/insulin aspart (IDegAsp) is a modern coformulation of ultra-long acting basal insulin degludec, with rapid-acting insulin aspart. IDegAsp provides effective, safe, well-tolerated glycemic control, with a low risk of hypoglycemia while allowing flexibility in meal patterns and timing of administration. This consensus statement describes a pragmatic framework to identify patients who may benefit from IDegAsp therapy. It highlights the utility of IDegAsp in type 2 diabetic patients who are insulin-naive, suboptimally controlled on basal or premixed insulin, or dissatisfied with basal-bolus regimens. It also describes potential IDegAsp usage in type 1 diabetic patients. PMID- 27366724 TI - Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum? AB - Diabetes and related complications are associated with long-term damage and failure of various organ systems. The line of demarcation between the pathogenic mechanisms of microvascular and macrovascular complications of diabetes and differing responses to therapeutic interventions is blurred. Diabetes induces changes in the microvasculature, causing extracellular matrix protein synthesis, and capillary basement membrane thickening which are the pathognomic features of diabetic microangiopathy. These changes in conjunction with advanced glycation end products, oxidative stress, low grade inflammation, and neovascularization of vasa vasorum can lead to macrovascular complications. Hyperglycemia is the principal cause of microvasculopathy but also appears to play an important role in causation of macrovasculopathy. There is thought to be an intersection between micro and macro vascular complications, but the two disorders seem to be strongly interconnected, with micro vascular diseases promoting atherosclerosis through processes such as hypoxia and changes in vasa vasorum. It is thus imperative to understand whether microvascular complications distinctly precede macrovascular complications or do both of them progress simultaneously as a continuum. This will allow re-focusing on the clinical issues with a unifying perspective which can improve type 2 diabetes mellitus outcomes. PMID- 27366725 TI - Hypothyroidism and obesity: An intriguing link. AB - According to common perception, hypothyroidism is held responsible for obesity. However, linking them causally is controversial. Overt hypothyroidism is associated with modest weight gain, but there is a lack of clarity regarding subclinical hypothyroidism. Novel view indicates that changes in thyroid stimulating hormone (TSH) could well be secondary to obesity. The increasing prevalence of obesity further confounds definition of normal TSH range in population studies. Thyroid autoantibody status may help in establishing the diagnosis of subclinical hypothyroidism in obesity. High leptin levels may play a role in the hyperthyrotropinemia of obesity and also increase susceptibility to thyroid autoimmunity and subsequent hypothyroidism. There is at most a modest effect of L-T4 treatment in overt hypothyroidism in inducing weight loss; benefit in subclinical hypothyroidism is not established with no data supporting thyroid hormone use in euthyroid obese patients. PMID- 27366726 TI - The neuroendocrinology of love. AB - Romantic love could be considered as a collection of activities associated with the acquisition and retention of emotions needed to survive and reproduce. These emotions change the individual's behavioural strategies in a way that will increase the likelihood of achieving these goals. Love may be defined as an emergent property of an ancient cocktail of neuropeptides and neurotransmitters. It appears that lust, attachment and attraction appear to be distinct but intertwined processes in the brain each mediated by its own neurotransmitters and circuits. These circuits feed on and reinforce each other. Sexual craving is mediated by testosterone and oestrogen and has the amygdala as an important centre. Attraction is mediated by hormones of stress and reward including dopamine, norepinephrine cortisol and the serotinergic system and has the nucleus accumbens the ventral tegmental area as key mediators. PMID- 27366727 TI - Insulin degludec and insulin degludec/insulin aspart in Ramadan: A single center experience. AB - This study aimed to document the utility and safety of insulin degludec (IDeg) and insulin degludec aspart (IDegAsp) in persons with type 2 diabetes, observing the Ramadan fast. An observational study was conducted at a single center, in the real world setting, on six persons who either switched to IDeg or IDegAsp a month before Ramadan or changed time of administration of IDegAsp at the onset of Ramadan, to keep the fast in a safe manner. Subjects were kept under regular monitoring and surveillance before, during, and after Ramadan, and counseled in an opposite manner. Four persons, who shifted from premixed insulin to IDegAsp, experienced a 12-18% dose reduction after 14 days. At the onset of Ramadan, the Suhur dose was reduced by 30%, and this remained unchanged during the fasting month. The Iftar dose had to be increased by 4 units. One person who shifted from neutral protamine hagedorn to IDeg demonstrated a 25% dose reduction at 20 days, without any further change in insulin requirement during Ramadan. One person who changed time of injection of IDegAsp from morning to night reported no change in dosage. No episode of major hypoglycemia was reported. IDeg and IDegAsp are effective, safe, and well-tolerated means of achieving glycemic control in persons with type 2 diabetes who wish to fast. PMID- 27366728 TI - Alternate-day dosing of linagliptin in type 2 diabetes patients controlled on once daily dose: A case series. AB - Linagliptin, a dipeptidyl peptidase 4 (DPP 4) inhibitor with a long terminal half life, significantly inhibits the DPP 4 enzyme at a steady state up to 48 h after the last dose. The present case series examined the hypothesis that linagliptin retains its efficacy during alternate day dosing in type 2 diabetes patients when switched over from once daily (OD) dosing. Eight type 2 diabetes patients maintaining stable glycosylated hemoglobin (HbA1c) with acceptable fasting plasma glucose and postprandial glucose levels and receiving linagliptin 5 mg OD for at least 6 weeks, with a stable dose of concomitant antidiabetic medications were given linagliptin 5 mg every alternate day. The median HbA1c while on the OD regimen was 6.1% (43 mmol/mol) (range: 5.8-6.9% [40-52 mmol/mol]) and median duration of diabetes was 7 years (range: 0.75-16 years). After a median follow-up period of 21weeks,the glycemic control was maintained in all patients similar to their baseline values (median HbA1c: 6.0% [42 mmol/mol], range: 5.1-7.1% [32-54 mmol/mol]). The body weight, fasting, and random glucose levels at baseline were also well maintained at the end of treatment. Optimal glycemic status maintained in our study population favors our hypothesis that linagliptin used alternate daily after switching from initial OD dose of the drug in patients on a stable background antidiabetic medications retains its efficacy. Paradoxically, alternate day dosing may affect compliance if the patient forgets when they took the last dose. Further studies including larger cohorts are needed to validate this finding and identify patients who can benefit from the alternate day regimen. PMID- 27366729 TI - Coexisting Turner's syndrome, Hashimoto's thyroiditis, and growth hormone deficiency. PMID- 27366730 TI - Biosimilar insulins: An unavoidable option in South-East Asia. PMID- 27366731 TI - Ketoacidosis in diabetic subjects treated with inhibitors of Na(+)-glucose co transporters type-2: New mechanisms? PMID- 27366732 TI - Reply to the editorial - "Only generics (drugs/names): Is India ready?". PMID- 27366733 TI - Mighty journals, mega trials, and modest points. PMID- 27366734 TI - Autoimmune polyglandular syndrome type II: Schimidt's syndrome, a unifying diagnosis in a case presenting with an uncommon combination of multiple endocrine disorders. PMID- 27366735 TI - Hyperparathyroidism in dentistry: Issues and challenges!! PMID- 27366736 TI - The association between urinary lgM excretion and diabetic retinopathy in diabetic patients. AB - BACKGROUND: Diabetic Retinopathy is one of the most common causes of blindness among adults. Microvascular complications may have common origins. The objective of the present study is to analyze the correlation between urinary IgM excretion and diabetic retinopathy based on the type of diabetes. METHODS: The present study is cross-sectional analytic and was carried out on 140 type2 diabetic patients (of which 70 patients diagnosed with retinopathy) and 76 type1 diabetic patients (of which 37 patients diagnosed with retinopathy). For every patient in each of the test groups, fasting plasma glucose, triglyceride, cholesterol, creatinin and HbA1c tests were done. The value of IgM, the albumin- to- creatinine ratio and the urine analysis test were also used to rule out the significant proteinuria of the patients. Then, IgM Index was measured using the following equation: Igm Index = Urine IgM/Urine Cr. RESULTS: The level of IgM index in the diabetic patients (type1 and type2) had no significant correlation with retinopathy. Cut point = 1.49, sensitivity = 0.703 and specificity = 0.308 in type1 diabetes were used for screen retinopathy. In type1 diabetic patients, the duration of diabetes had a significant correlation with urinary protein while in type 2 diabetic patients, the diabetes duration and HbA1c were significantly correlated with retinopathy. CONCLUSION: The results of this study demonstrate that the level of urinary IgM in diabetic patients has no difference in those who have or lack retinopathy, but the urinary IgM level of more than 1.49 mg/dl can be considered as a cut point in type1 diabetic patients to screen retinopathy. PMID- 27366737 TI - Genetic Variation of Flavonols Quercetin, Myricetin, and Kaempferol in the Sri Lankan Tea (Camellia sinensis L.) and Their Health-Promoting Aspects. AB - Flavonol glycosides in tea leaves have been quantified as aglycones, quercetin, myricetin, and kaempferol. Occurrence of the said compounds was reported in fruits and vegetable for a long time in association with the antioxidant potential. However, data on flavonols in tea were scanty and, hence, this study aims to envisage the flavonol content in a representative pool of accessions present in the Sri Lankan tea germplasm. Significant amounts of myricetin, quercetin, and kaempferol have been detected in the beverage type tea accessions of the Sri Lankan tea germplasm. This study also revealed that tea is a good source of flavonol glycosides. The Camellia sinensis var. sinensis showed higher content of myricetin, quercetin, and total flavonols than var. assamica and ssp. lasiocalyx. Therefore flavonols and their glycosides can potentially be used in chemotaxonomic studies of tea germplasm. The nonbeverage type cultivars, especially Camellia rosaflora and Camellia japonica Red along with the exotic accessions resembling China type, could be useful in future germplasm studies because they are rich sources of flavonols, namely, quercetin and kaempferol, which are potent antioxidants. The flavonol profiles can be effectively used in choosing parents in tea breeding programmes to generate progenies with a wide range of flavonol glycosides. PMID- 27366738 TI - Syntaxin 5 Overexpression and beta-Amyloid 1-42 Accumulation in Endoplasmic Reticulum of Hippocampal Cells in Rat Brain Induced by Ozone Exposure. AB - Oxidative stress is a risk factor for Alzheimer's disease and it is currently accepted that oxidative damage precedes the overproduction of A42 peptide. We have reported that ozone causes oxidative stress inducing neurodegeneration in the brain of rats. It is associated with A42 overproduction and intracellular accumulation in hippocampus. Organelles like mitochondria, intracellular membranes, and endoplasmic reticulum have been identified as sites of A42 production and accumulation affecting cellular metabolism. However whether ozone exposure induces overproduction and/or accumulation of A42 in endoplasmic reticulum has not been studied. We evaluated this effect in the endoplasmic reticulum of hippocampal cells of rats exposed chronically to low doses of ozone (0.25 ppm) at 7, 15, 30, 60, and 90 days. The effect of the presence of A42 in endoplasmic reticulum was analyzed evaluating the expression of the chaperone Syntaxin 5. Our results show an accumulation of A42 peptide in this organelle. It was observed by immunofluorescence and by WB in endoplasmic fractions from hippocampal cells of rats at 60 and 90 days of treatment. Significant overexpression of the chaperone Syntaxin 5 at 60 and 90 days of treatment was observed ((*) P < 0.05). These results indicate that the exposure to environmental pollutants could be involved as a risk factor for neurodegenerative processes. PMID- 27366739 TI - Fibronectin-Grafted Titanium Dental Implants: An In Vivo Study. AB - Modification of the physiochemical properties of titanium surfaces using glow discharge plasma (GDP) and fibronectin coating has been shown to enhance the surface hydrophilicity, surface roughness, cell adhesion, migration, and proliferation. This in vivo study aimed to evaluate the bone integration efficacy of a biologically modified implant surface. Two different surface-modified implants (Ar-GDP and GDP-fib) were placed in the mandibular premolar area of six beagle dogs for 2-8 weeks. Three techniques [histologic evaluation, resonance frequency analysis (RFA), and microcomputed tomography (micro-CT) evaluation] were used to detect the implant stability and bone-implant contact. The implant stability quotient values of GDP-fib implants were significantly greater than the Ar-GDP implants at 2 and 4 weeks (P < 0.01). The bone volume/total volume ratio of GDP-fib implants was greater than the Ar-GDP implants in micro-CT evaluation. A high positive correlation was observed between RFA and micro-CT measurements. At 2 weeks, osteoblasts were seen to line the implant surface, and multinuclear osteoclasts could be seen on the surface of old parent bone. After 8 weeks, a majority of the space in the wound chamber appeared to be replaced by bone. Enhancement of the stability of biologically modified implants was proved by the results of RFA, micro-CT, and histological analysis. This enhanced stability may help fasten treatment and be clinically beneficial. PMID- 27366740 TI - Effect of High Dietary Tryptophan on Intestinal Morphology and Tight Junction Protein of Weaned Pig. AB - Tryptophan (Trp) plays an essential role in pig behavior and growth performances. However, little is known about Trp's effects on tight junction barrier and intestinal health in weaned pigs. In the present study, twenty-four (24) weaned pigs were randomly assigned to one of the three treatments with 8 piglets/treatments. The piglets were fed different amounts of L-tryptophan (L Trp) as follows: 0.0%, 0.15, and 0.75%, respectively, named zero Trp (ZTS), low Trp (LTS), and high Trp (HTS), respectively. No significant differences were observed in average daily gain (ADG), average daily feed intake (ADFI), and gain: feed (G/F) ratio between the groups. After 21 days of the feeding trial, results showed that dietary Trp significantly increased (P < 0.05) crypt depth and significantly decreased (P < 0.05) villus height to crypt depth ratio (VH/CD) in the jejunum of pig fed HTS. In addition, pig fed HTS had higher (P < 0.05) serum diamine oxidase (DAO) and D-lactate. Furthermore, pig fed HTS significantly decreased mRNA expression of tight junction proteins occludin and ZO-1 but not claudin-1 in the jejunum. The number of intraepithelial lymphocytes and goblet cells were not significantly different (P > 0.05) between the groups. Collectively, these data suggest that dietary Trp supplementation at a certain level (0.75%) may negatively affect the small intestinal structure in weaned pig. PMID- 27366741 TI - Soft Tissue Response to Titanium Abutments with Different Surface Treatment: Preliminary Histologic Report of a Randomized Controlled Trial. AB - The aim of this preliminary prospective RCT was to histologically evaluate peri implant soft tissues around titanium abutments treated using different cleaning methods. Sixteen patients were randomized into three groups: laboratory customized abutments underwent Plasma of Argon treatment (Plasma Group), laboratory customized abutments underwent cleaning by steam (Steam Group), and abutments were used as they came from industry (Control Group). Seven days after the second surgery, soft tissues around abutments were harvested. Samples were histologically analyzed. Soft tissues surrounding Plasma Group abutments predominantly showed diffuse chronic infiltrate, almost no acute infiltrate, with presence of few polymorphonuclear neutrophil granulocytes, and a diffuse presence of collagenization bands. Similarly, in Steam Group, the histological analysis showed a high variability of inflammatory expression factors. Tissues harvested from Control Group showed presence of few neutrophil granulocytes, moderate presence of lymphocytes, and diffuse collagenization bands in some sections, while they showed absence of acute infiltrate in 40% of sections. However, no statistical difference was found among the tested groups for each parameter (p > 0.05). Within the limit of the present study, results showed no statistically significant difference concerning inflammation and healing tendency between test and control groups. PMID- 27366742 TI - The Influence of Irradiation Time and Layer Thickness on Elution of Triethylene Glycol Dimethacrylate from SDR(r) Bulk-Fill Composite. AB - Objective. This study aimed to evaluate triethylene glycol dimethacrylate (TEGDMA) elution from SDR bulk-fill composite. Methods. Three groups of samples were prepared, including samples polymerized in a 4 mm layer for 20 s, in a 4 mm layer for 40 s, and in a 2 mm layer for 20 s. Elution of TEGDMA into 100% ethanol, a 75% ethanol/water solution, and distilled water was studied. The TEGDMA concentration was measured using HPLC. Results. The TEGDMA concentration decreased in the following order: 100% ethanol > 75% ethanol > distilled water. Doubling the energy delivered to the 4 mm thick sample caused decrease (p < 0.05) in TEGDMA elution to distilled water. In ethanol solutions, the energy increase had no influence on TEGDMA elution. Decreasing the sample thickness resulted in decrease (p < 0.05) in TEGDMA elution for all the solutions. Conclusions. The concentration of eluted TEGDMA and the elution time were both strongly affected by the hydrophobicity of the solvent. Doubling the energy delivered to the 4 mm thick sample did not decrease the elution of TEGDMA but did decrease the amount of the monomer available to less aggressive solvents. Elution of TEGDMA was also correlated with the exposed sample surface area. Clinical Relevance. Decreasing the SDR layer thickness decreases TEGDMA elution. PMID- 27366743 TI - Assessment of Diagnostic and Prognostic Role of Copeptin in the Clinical Setting of Sepsis. AB - The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism). Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L), calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment. PMID- 27366744 TI - Involvement of Hormone- and ROS-Signaling Pathways in the Beneficial Action of Humic Substances on Plants Growing under Normal and Stressing Conditions. AB - The importance of soil humus in soil fertility has been well established many years ago. However, the knowledge about the whole mechanisms by which humic molecules in the rhizosphere improve plant growth remains partial and rather fragmentary. In this review we discuss the relationships between two main signaling pathway families that are affected by humic substances within the plant: one directly related to hormonal action and the other related to reactive oxygen species (ROS). In this sense, our aims are to try the integration of all these events in a more comprehensive model and underline some points in the model that remain unclear and deserve further research. PMID- 27366745 TI - Modulation of Circulating MicroRNAs Levels during the Switch from Clopidogrel to Ticagrelor. AB - Background. Circulating microRNAs are appealing biomarkers to monitor several processes underlying cardiovascular diseases. Platelets are a major source for circulating microRNAs. Interestingly, the levels of specific microRNAs were reported to correlate with the level of platelet activation. The aim of the present study was to test whether the treatment with the novel antiplatelet agent, ticagrelor, is associated with modulation in the levels of key platelet derived microRNAs. Methods and Results. Patients were randomly selected from those participating in the SHIFT-OVER study, in which we had previously evaluated the effect of the therapeutic switch from clopidogrel to ticagrelor on platelet aggregation. Circulating levels of selected microRNAs were measured before and after the therapeutic switch from a dual antiplatelet therapy including acetylsalicylic acid (ASA) and clopidogrel to the more potent ticagrelor. Interestingly, the circulating levels of miR-126 (p = 0.030), miR-223 (p = 0.044), and miR-150 (p = 0.048) were significantly reduced, while the levels of miR-96 were increased (p = 0.038). No substantial differences were observed for the remaining microRNAs. Conclusions. Switching from a dual antiplatelet treatment with clopidogrel to ticagrelor is associated with significant modulation in the circulating levels of specific microRNAs. If confirmed in larger, independent cohorts, our results pave the way for the use of circulating microRNAs as biomarkers of platelets activity in response to specific pharmacological treatments. PMID- 27366746 TI - NLRP3 Activation Was Regulated by DNA Methylation Modification during Mycobacterium tuberculosis Infection. AB - Mycobacterium tuberculosis (Mtb) infection activates the NLRP3 inflammasome in macrophages and dendritic cells. Much attention has been paid to the mechanisms for regulation of NLRP3 against Mtb. However, whether epigenetic mechanisms participated in NLRP3 activation is still little known. Here we showed that NLRP3 activation was regulated by DNA methylation modification. Mtb infection promoted NLRP3 activation and inflammatory cytokines expression. NLRP3 promoter was cloned and subsequently identified by Dual-Luciferase Reporter System. The results showed that NLRP3 promoter activity was decreased after methylation by DNA methylase Sss I in vitro. Meanwhile, DNA methyltransferases inhibitor DAC could upregulate the expression of NLRP3. Furthermore, promoter region of NLRP3 gene was demethylated after Mtb H37Rv strain infection. These data revealed that DNA methylation was involved in NLRP3 inflammasome activation during Mtb infection and provided a new insight into the relationship between host and pathogens. PMID- 27366748 TI - Subcritical Water Technology for Enhanced Extraction of Biochemical Compounds from Chlorella vulgaris. AB - Subcritical water extraction (SWE) technology has been used for the extraction of active compounds from different biomass materials with low process cost, mild operating conditions, short process times, and environmental sustainability. With the limited application of the technology to microalgal biomass, this work investigates parametrically the potential of subcritical water for high-yield extraction of biochemicals such as carbohydrates and proteins from microalgal biomass. The SWE process was optimized using central composite design (CCD) under varying process conditions of temperature (180-374 degrees C), extraction time (1 20 min), biomass particulate size (38-250 MUm), and microalgal biomass loading (5 40 wt.%). Chlorella vulgaris used in this study shows high volatile matter (83.5 wt.%) and carbon content (47.11 wt.%), giving advantage as a feedstock for biofuel production. The results showed maximum total carbohydrate content and protein yields of 14.2 g/100 g and 31.2 g/100 g, respectively, achieved under the process conditions of 277 degrees C, 5% of microalgal biomass loading, and 5 min extraction time. Statistical analysis revealed that, of all the parameters investigated, temperature is the most critical during SWE of microalgal biomass for protein and carbohydrate production. PMID- 27366747 TI - Animal Models of Uveal Melanoma: Methods, Applicability, and Limitations. AB - Animal models serve as powerful tools for investigating the pathobiology of cancer, identifying relevant pathways, and developing novel therapeutic agents. They have facilitated rapid scientific progress in many tumor entities. However, for establishing a powerful animal model of uveal melanoma fundamental challenges remain. To date, no animal model offers specific genetic attributes as well as histologic, immunologic, and metastatic features of uveal melanoma. Syngeneic models with intraocular injection of cutaneous melanoma cells may suit best for investigating immunologic/tumor biology aspects. However, differences between cutaneous and uveal melanoma regarding genetics and metastasis remain problematic. Human xenograft models are widely used for evaluating novel therapeutics but require immunosuppression to allow tumor growth. New approaches aim to establish transgenic mouse models of spontaneous uveal melanoma which recently provided preliminary promising results. Each model provides certain benefits and may render them suitable for answering a respective scientific question. However, all existing models also exhibit relevant limitations which may have led to delayed research progress. Despite refined therapeutic options for the primary ocular tumor, patients' prognosis has not improved since the 1970s. Basic research needs to further focus on a refinement of a potent animal model which mimics uveal melanoma specific mechanisms of progression and metastasis. This review will summarise and interpret existing animal models of uveal melanoma including recent advances in the field. PMID- 27366749 TI - Plant Growth Biostimulants Based on Different Methods of Seaweed Extraction with Water. AB - We explored two methods for obtaining aqueous extracts: boiling and soaking of Baltic seaweeds (EB and ES, resp.). Algal extracts were characterized in terms of polyphenols, micro- and macroelements, lipids content, and antibacterial properties. The utilitarian properties were examined in the germination tests on Lepidium sativum for three extract dilutions (0.5, 2.5, and 10%). It was found that the extracts were similar in micro- and macroelement concentrations. Water was proved to be a good solvent to extract phenolic compounds. The algal extract produced by soaking biomass did not show inhibitory effect on Escherichia coli and Staphylococcus aureus. Only the boiled extract had an inhibitory activity against E. coli. Germination tests revealed a positive influence of the bioproducts on the cultivated plants. In the group treated with 10% EB, plants were 13% longer than in the control group; the content of elements B, Mo, Zn, and Na in the group treated with 10% ES was higher by 76%, 48%, 31%, and 59% than in the control group, respectively; the content of chlorophyll was 2.5 times higher in 0.5% ES than in the control group. Extracts showed the slight impact on the morphology of plants. PMID- 27366750 TI - Prevalence of Extended Spectrum beta-Lactamase and Antimicrobial Susceptibility Pattern of Clinical Isolates of Pseudomonas from Patients of Khyber Pakhtunkhwa, Pakistan. AB - Majority of gram negative pathogenic bacteria are responsible for extended spectrum beta-lactamases (ESBLs) production, which show resistance to some newer generation of antibiotics. The study was aimed at evaluating the prevalence of ESBL and antibiotic susceptibility pattern of Pseudomonas isolates collected during 2010 to 2014 from tertiary care hospitals of Peshawar, Pakistan. Out of 3450 samples, 334 Pseudomonas spp. isolates comprised of 232 indoor and 102 outdoor patients were obtained from different specimens and their susceptibility pattern was determined against 20 antibiotics. Antimicrobial susceptibility testing was carried out using the Kirby-Bauer agar diffusion method and ESBL production was detected by Synergy Disc Diffusion technique. The mean age group of the patients was 29.9 + 9.15 years. Meronem showed best activity (91.02%) from class carbapenem, beta-lactam and beta-lactamase inhibitors exhibited 69.16% activity, and doxycycline had a diminished activity (10.18%) to Pseudomonas spp. Outdoor isolates were more resistant than the indoor and during the course of the study the sensitivity rate of antibiotics was gradually reducing. ESBL production was observed in 44.32% while the remaining was non-ESBL. The moderate active antibiotics were amikacin (50.7%), SCF (51.4%), TZP (52.7%), and MXF (54.1%) among ESBL producing isolates. Lack of antibiotic policy, irrational uses (3GCs particularly), and the emergence of antibiotic resistant organisms in hospitals may be causes of high antibiotic resistance. PMID- 27366751 TI - Efficacy of Linezolid and Fosfomycin in Catheter-Related Biofilm Infection Caused by Methicillin-Resistant Staphylococcus aureus. AB - As long-standing clinical problems, catheter-related infections and other chronic biofilm infections are more difficult to treat due to the high antibiotic resistance of biofilm. Therefore, new treatments are needed for more effective bacteria clearance. In this study, we evaluated the antibacterial activities of several common antibiotics alone and their combinations against biofilm-embedded methicillin-resistant staphylococcus aureus (MRSA) infections, both in vitro and in vivo. In brief, fosfomycin, levofloxacin, and rifampin alone or in combination with linezolid were tested in vitro against planktonic and biofilm-embedded MRSA infection in three MRSA stains. The synergistic effects between linezolid and the other three antibiotics were assessed by fractional inhibitory concentration index (FICI) and time-kill curves, where the combination of linezolid plus fosfomycin showed the best synergistic effect in all strains. For further evaluation in vivo, we applied the combination of linezolid and fosfomycin in a catheter-related biofilm rat model and found that viable bacteria counts in biofilm were significantly reduced after treatment (P < 0.05). In summary, we have shown here that the combination of linezolid and fosfomycin treatment had improved therapeutic effects on biofilm-embedded MRSA infection both in vitro and in vivo, which provided important basis for new clinical therapy development. PMID- 27366752 TI - Influence of a 10-Day Mimic of Our Ancient Lifestyle on Anthropometrics and Parameters of Metabolism and Inflammation: The "Study of Origin". AB - Chronic low-grade inflammation and insulin resistance are intimately related entities that are common to most, if not all, chronic diseases of affluence. We hypothesized that a short-term intervention based on "ancient stress factors" may improve anthropometrics and clinical chemical indices. We executed a pilot study of whether a 10-day mimic of a hunter-gatherer lifestyle favorably affects anthropometrics and clinical chemical indices. Fifty-five apparently healthy subjects, in 5 groups, engaged in a 10-day trip through the Pyrenees. They walked 14 km/day on average, carrying an 8-kilo backpack. Raw food was provided and self prepared and water was obtained from waterholes. They slept outside in sleeping bags and were exposed to temperatures ranging from 12 to 42 degrees C. Anthropometric data and fasting blood samples were collected at baseline and the study end. We found important significant changes in most outcomes favoring better metabolic functioning and improved anthropometrics. Coping with "ancient mild stress factors," including physical exercise, thirst, hunger, and climate, may influence immune status and improve anthropometrics and metabolic indices in healthy subjects and possibly patients suffering from metabolic and immunological disorders. PMID- 27366753 TI - Effect of TRPV4-p38 MAPK Pathway on Neuropathic Pain in Rats with Chronic Compression of the Dorsal Root Ganglion. AB - The aim of this study was to investigate the relationships among TRPV4, p38, and neuropathic pain in a rat model of chronic compression of the dorsal root ganglion. Mechanical allodynia appeared after CCD surgery, enhanced via the intrathecal injection of 4alpha-phorbol 12,13-didecanoate (4alpha-PDD, an agonist of TRPV4) and anisomycin (an agonist of p38), but was suppressed by Ruthenium Red (RR, an inhibitor of TRPV4) and SB203580 (an inhibitor of p38). The protein expressions of p38 and P-p38 were upregulated by 4alpha-PDD and anisomycin injection but reduced by RR and SB203580. Moreover, TRPV4 was upregulated by 4alpha-PDD and SB203580 and downregulated by RR and anisomycin. In DRG tissues, the numbers of TRPV4- or p38-positive small neurons were significantly changed in CCD rats, increased by the agonists, and decreased by the inhibitors. The amplitudes of ectopic discharges were increased by 4alpha-PDD and anisomycin but decreased by RR and SB203580. Collectively, these results support the link between TRPV4 and p38 and their intermediary role for neuropathic pain in rats with chronic compression of the dorsal root ganglion. PMID- 27366754 TI - Formation of Aldehydic Phosphatidylcholines during the Anaerobic Decomposition of a Phosphatidylcholine Bearing the 9-Hydroperoxide of Linoleic Acid. AB - Lipid oxidation-derived carbonyl compounds are associated with the development of various physiological disorders. Formation of most of these products has recently been suggested to require further reactions of oxygen with lipid hydroperoxides. However, in rat and human tissues, the formation of 4-hydroxy-2-nonenal is greatly elevated during hypoxic/ischemic conditions. Furthermore, a previous study found an unexpected result that the decomposition of a phosphatidylcholine (PC) bearing the 13-hydroperoxide of linoleic acid under a nitrogen atmosphere afforded 9-oxononanoyl-PC rather than 13-oxo-9,11-tridecadienoyl-PC as the main aldehydic PC. In the present study, products of the anaerobic decomposition of a PC bearing the 9-hydroperoxide of linoleic acid were analysed by electrospray ionization mass spectrometry. 9-Oxononanoyl-PC (ONA-PC) and several well-known bioactive aldehydes including 12-oxo-9-hydroperoxy-(or oxo or hydroxy)-10 dodecenoyl-PCs were detected. Hydrolysis of the oxidized PC products, methylation of the acids obtained thereby, and subsequent gas chromatography-mass spectroscopy with electron impact ionization further confirmed structures of some of the key aldehydic PCs. Novel, hydroxyl radical-dependent mechanisms of formation of ONA-PC and peroxyl-radical dependent mechanisms of formation of the rest of the aldehydes are proposed. The latter mechanisms will mainly be relevant to tissue injury under hypoxic/anoxic conditions, while the former are relevant under both normoxia and hypoxia/anoxia. PMID- 27366755 TI - Combined V-Y Fasciocutaneous Advancement and Gluteus Maximus Muscle Rotational Flaps for Treating Sacral Sores. AB - The sacral area is the most common site of pressure sore in bed-ridden patients. Though many treatment methods have been proposed, a musculocutaneous flap using the gluteus muscles or a fasciocutaneous flap is the most popular surgical option. Here, we propose a new method that combines the benefits of these 2 methods: combined V-Y fasciocutaneous advancement and gluteus maximus muscle rotational flaps. A retrospective review was performed for 13 patients who underwent this new procedure from March 2011 to December 2013. Patients' age, sex, accompanying diseases, follow-up duration, surgical details, complications, and recurrence were documented. Computed tomography was performed postoperatively at 2 to 4 weeks and again at 4 to 6 months to identify the thickness and volume of the rotational muscle portion. After surgery, all patients healed within 1 month; 3 patients experienced minor complications. The average follow-up period was 13.6 months, during which time 1 patient had a recurrence (recurrence rate, 7.7%). Average thickness of the rotated muscle was 9.43 mm at 2 to 4 weeks postoperatively and 9.22 mm at 4 to 6 months postoperatively (p = 0.087). Muscle thickness had not decreased, and muscle volume was relatively maintained. This modified method is relatively simple and easy for reconstructing sacral sores, provides sufficient padding, and has little muscle donor-site morbidity. PMID- 27366757 TI - Diabetic Foot: Current Status and Future Prospects. PMID- 27366756 TI - Serotonin- and Dopamine-Related Gene Expression in db/db Mice Islets and in MIN6 beta-Cells Treated with Palmitate and Oleate. AB - High circulating nonesterified fatty acids (NEFAs) concentration, often reported in diabetes, leads to impaired glucose-stimulated insulin secretion (GSIS) through not yet well-defined mechanisms. Serotonin and dopamine might contribute to NEFA-dependent beta-cell dysfunction, since extracellular signal of these monoamines decreases GSIS. Moreover, palmitate-treated beta-cells may enhance the expression of the serotonin receptor Htr2c, affecting insulin secretion. Additionally, the expression of monoamine-oxidase type B (Maob) seems to be lower in islets from humans and mice with diabetes compared to nondiabetic islets, which may lead to increased monoamine concentrations. We assessed the expression of serotonin- and dopamine-related genes in islets from db/db and wild-type (WT) mice. In addition, the effect of palmitate and oleate on the expression of such genes, 5HT content, and GSIS in MIN6 beta-cell was determined. Lower Maob expression was found in islets from db/db versus WT mice and in MIN6 beta-cells in response to palmitate and oleate treatment compared to vehicle. Reduced 5HT content and impaired GSIS in response to palmitate (-25%; p < 0.0001) and oleate (-43%; p < 0.0001) were detected in MIN6 beta-cells. In conclusion, known defects of GSIS in islets from db/db mice and MIN6 beta-cells treated with NEFAs are accompanied by reduced Maob expression and reduced 5HT content. PMID- 27366758 TI - No place for /h/: an ERP investigation of English fricative place features. AB - The representational format of speech units in long-term memory is a topic of debate. We present novel event-related brain potential evidence from the Mismatch Negativity (MMN) paradigm that is compatible with abstract, non-redundant feature based models like the Featurally Underspecified Lexicon (FUL). First, we show that the fricatives /s/ and /f/ display an asymmetric pattern of MMN responses, which is predicted if /f/ has a fully specified place of articulation ([Labial]) but /s/ does not ([Coronal], which is lexically underspecified). Second, we show that when /s/ and /h/ are contrasted, no such asymmetric MMN pattern occurs. The lack of asymmetry suggests both that (i) oral and laryngeal articulators are represented distinctly and that (ii) /h/ has no oral place of articulation in long-term memory. The lack of asymmetry between /s/ and /h/ is also in-line with traditional feature-geometric models of lexical representations. PMID- 27366759 TI - Aorta Atherosclerosis Lesion Analysis in Hyperlipidemic Mice. AB - Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries. Apolipoprotein E-deficient (ApoE-/-) mice are used as experimental models to study human atherosclerosis. ApoE-/- mice are constitutively hyperlipidemic and develop intima plaques that resemble human plaques. Various issues including experimental design for lesion analysis, dietary conditions, isolation of the aorta, staining methods, morphometry, group size, age, the location within the arterial tree, and statistical analyses are important parameters that need to be addressed to obtain robust data. Here, we provide detailed methods to quantify aorta atherosclerosis. PMID- 27366760 TI - Zika virus outbreak: an overview of the experimental therapeutics and treatment. AB - Zika virus (ZIKV) infection is a new emerging threat around the globe which might be responsible for microcephaly and Guillain-Barre syndrome in the infants. Recently, ZIKV outbreak has caused a public health crisis in Brazil after being linked to a sharp increase in birth defects. ZIKV is ssRNA virus belongs to the family Flaviviridae. It is mainly transmitted by mosquito bite specifically Aedes species and disease symptoms include fever, joint pain, muscle pain, rash, conjunctivitis, and headache. The reservoir of ZIKV is still not known. Protection at personal level by avoiding mosquito bite would help to reduce the incidence of the disease. Control of ZIKV infection by vaccination or antiviral drug either from modern, complementary and alternative medicines may be considered to be one of the most effective strategies in the long run. Large scale immunization of susceptible human population is highly required to prevent this deadly disease. Attempts should be made as soon as possible to develop effective vaccines or antiviral to prevent ZIKV infection. This article provides a current overview of the experimental therapeutics and treatment options based on modern, complementary and alternative medicines. PMID- 27366761 TI - Human papillomavirus (HPV) infection: a Mozambique overview. AB - Human Papillomavirus is agent of the most common sexually transmitted disease which is able to infect mucosal and cutaneous membranes of the anogenital region, upper aerodigestive tract, and other head and neck mucosal regions. Although mainly HPV infection can be asymptomatic and transient, it may persist and give rise to various lesions such as warts, condyloma dysplasia and cancers depending on low or high risk type of HPV infection. Moreover, growing recent evidence suggests a role of this virus in male and female fertility. To date no effective prevention, test, treatment and control strategies are provided for people in developing countries despite the reported high incidence of HPV both in women and men. This paper reviews the more recent literature about HPV infection highlighting epidemiology, related pathologies and possible fertility effects of HPV in male and female with particular attention to the Mozambique context. PMID- 27366762 TI - Design and evaluation of reverse transcription nested PCR primers for the detection of betanodavirus in finfish. AB - Viral encephalopathy and retinopathy otherwise known as viral nervous necrosis (VNN) is a neuropathological condition affecting more than 50 fish species worldwide, mostly marine. Different PCR protocols with specific primers were reported from many countries for confirmation of VNN in fishes. In the present study, two pairs of primers were designed and evaluated for the diagnosis of clinical and subclinical cases of infections from field. These primers designated as BARL-F1/BARL-R1 amplified a 902 bp product in the variable region (T4) of the coat protein gene by first step PCR. Nested PCR primers BARL-F2/BARL-R2 amplified a fragment of 313 bp. The results were comparable with other commonly used primer sets such as F2/R3 and RG668f/RG919r primers. These new primers could detect betanodavirus in standard reference samples containing low, moderate and high viral load. Known positive and negative control samples of fish also revealed a predictive value of 100 % by RT-PCR diagnosis. PMID- 27366763 TI - The emergence and consistency of influenza strains causing influenza like illness in Himachal Pradesh, India. AB - The present study offers the status of ongoing surveillance influenza at National Influenza Surveillance Centre (NISC), Central Research Institute (CRI), Kasauli for the emergence and consistency of influenza strains for current as well as over a period of three decades in Solan, Himachal Pradesh. From 1980 to 2015, various clinical centers of Himachal reported counts of influenza-like illness (fever including cough or sore throat). During these years, the respiratory specimens of 6581 patients showing influenza-like illness were collected. The incidence of visits had been calculated for influenza-like illness using the size of the patient population, and the incidence attributable to influenza was extrapolated from the proportion of patients with positive tests. Up to 2008 the egg inoculation method was used for the isolation and detection of influenza strains but in 2009 a RT-PCR equipped, fabricated BSL-3 laboratory was implanted at CRI for the isolation and detection of influenza strains. The reagents, primers and probes were supplied by NCDC, Delhi. Since 1980, 319 influenza isolates has been identified and isolated at NISC. Among these 282 were isolated by egg propagation method while 37 were processed by RT-PCR. Influenza incidence varied with age groups and by season after the pandemic of 2009 influenza A, H1N1. High levels of influenza virus circulation, especially in young children, emphasize the need for additional efforts to increase the uptake of influenza vaccines and anti-virals. PMID- 27366764 TI - Ebolavirus evolves in human to minimize the detection by immune cells by accumulating adaptive mutations. AB - The current outbreak of Zaire ebolavirus (EBOV) lasted longer than the previous outbreaks and there is as yet no proven treatment or vaccine available. Understanding host immune pressure and associated EBOV immune evasion that drive the evolution of EBOV is vital for diagnosis as well as designing a highly effective vaccine. The aim of this study was to deduce adaptive selection pressure acting on each amino acid sites of EBOV responsible for the recent 2014 outbreak. Multiple statistical methods employed in the study include SLAC, FEL, REL, IFEL, FUBAR and MEME. Results show that a total of 11 amino acid sites from sGP and ssGP, and 14 sites from NP, VP40, VP24 and L proteins were inferred as positively and negatively selected, respectively. Overall, the function of 11 out of 25 amino acid sites under selection pressure exactly found to be involved in T cell and B-cell epitopes. We identified that the EBOV had evolved through purifying selection pressure, which is a predictor that is known to aid the virus to adapt better to the human host and subsequently reduce the efficiency of existing immunity. Furthermore, computational RNA structure prediction showed that the three synonymous nucleotide mutations in NP gene altered the RNA secondary structure and optimal base-pairing energy, implicating a possible effect on genome replication. Here, we have provided evidence that the EBOV strains involved in the recent 2014 outbreak have evolved to minimize the detection by T and B cells by accumulating adaptive mutations to increase the survival fitness. PMID- 27366765 TI - Association of tomato leaf curl Sudan virus with leaf curl disease of tomato in Jeddah, Saudi Arabia. AB - Tomato is an important vegetable crop and its production is adversely affected by leaf curl disease caused by begomovirus. Leaf curl disease is a serious concern for tomato crops caused by begomovirus in Jeddah, Kingdom of Saudi Arabia. Tomato leaf curl disease has been shown to be mainly caused either by tomato leaf curl Sudan virus or tomato yellow leaf curl virus as well as tomato leaf curl Oman virus. Many tomato plants infected with monopartite begomoviruses were also found to harbor a symptom enhancing betasatellites. Here we report the association of tomato leaf curl Sudan virus causing leaf curl disease of tomato in Jeddah, Kingdom of Saudi Arabia. The complete genome sequence analysis showed highest (99.9 %) identity with tomato leaf curl Sudan virus causing leaf curl disease in Arabian Peninsula. In phylogenetic relationships analysis, the identified virus formed closest cluster with tomato leaf curl Sudan virus. In recombination analysis study, the major parent was identified as tomato leaf curl Sudan virus. Findings of this study strongly supports the associated virus is a variant of tomato leaf curl Sudan virus causing disease in Sudan, Yemen and Arabian Peninsula. The betasatellites sequence analysis showed highest identity (99.8 %) with tomato leaf curl betasatellites-Amaranthus-Jeddah. The phylogenetic analysis result based on betasatellites formed closed cluster with tomato yellow leaf curl Oman betasatellites. The importance of these findings and occurrence of begomovirus in new geographic regions causing leaf curl disease of tomato in Jeddah, Kingdom of Saudi Arabia are discussed. PMID- 27366766 TI - Molecular characterization of banana bunchy top virus isolate from Sri Lanka and its genetic relationship with other isolates. AB - Bunchy top disease of banana caused by Banana bunchy top virus (BBTV, genus Babuvirus family Nanoviridae) is one of the most important constraints in production of banana in the different parts of the world. Six genomic DNA components of BBTV isolate from Kandy, Sri Lanka (BBTV-K) were amplified by polymerase chain reaction (PCR) with specific primers using total DNA extracted from banana tissues showing typical symptoms of bunchy top disease. The amplicons were of expected size of 1.0-1.1 kb, which were cloned and sequenced. Analysis of sequence data revealed the presence of six DNA components; DNA-R, DNA-U3, DNA-S, DNA-N, DNA-M and DNA-C for Sri Lanka isolate. Comparisons of sequence data of DNA components followed by the phylogenetic analysis, grouped Sri Lanka-(Kandy) isolate in the Pacific Indian Oceans (PIO) group. Sri Lanka-(Kandy) isolate of BBTV is classified a new member of PIO group based on analysis of six components of the virus. PMID- 27366767 TI - Evidence of genetic drift and reassortment in infectious bursal disease virus and emergence of outbreaks in poultry farms in India. AB - Recurrent outbreaks of infectious bursal disease (IBD) have become a burning problem to the poultry industry worldwide. Here, we performed genetic analysis of IBD virus (IBDV) field isolates from recent outbreaks in various poultry farms in India. The sequence analysis of IBDV VP2 hypervariable region revealed amino acid pattern similar to that of very virulent (222A, 242I, 253Q, 256I, 272I, 279D, 284A, 294I, 299S and 330S) and intermediate plus virulent (222A, 242I, 253Q, 256I, 272T, 279N, 284A, 294I, 299S and 330S) type whereas analysis of VP1 revealed presence of sequence similar to that of very virulent (61I, 145T) and unique (61I, 141I, 143D, 145S) type in field isolates. Among the eight field isolates, two isolates contained very virulent type VP2 and unique type VP1, three contained intermediate plus virulent type VP2 and unique type VP1 whereas five contained both VP2 and VP1 of very virulent type. The phylogenetic analysis based on VP2 nucleotide sequence showed clustering of all eight isolates close to known very virulent strains whereas based on VP1, five isolates formed unique cluster and three isolates were placed close to very virulent strains. The isolates forming unique VP1 cluster showed highest similarity with classical virulent IBDVs suggesting their possible evolution from segment B of non-very virulent IBDVs. Interestingly, these five isolates were responsible for outbreaks in four different farms located at three different geographic locations in India. These observations indicates genetic reassortment between segment A and segment B from co-infecting IBDV strains leading to emergence of very virulent strains and their widespread prevalence in Indian poultry farms. The presence of 272I and 279D in VP2 protein of five field isolates may explain possible cause of Gumboro intermediate plus vaccine failure in prevention of the outbreaks. However, mortality caused by other three strains which are antigenically similar to VP1 of intermediate plus vaccine strains could not be explained and the possible role of their unique VP1 in enhancing the pathogenesis needs to be investigated further. PMID- 27366768 TI - Antiviral activity of the oseltamivir and Melissa officinalis L. essential oil against avian influenza A virus (H9N2). AB - Lemon balm derivatives are going to acquire a novelty as natural and potent remedy for treatment of viral infections since the influenza viruses are developing resistance to the current antivirals widely. Oseltamivir, Melissa officinalis essential oil (MOEO) and their synergistic efficacy against avian influenza virus (AIV) subtype H9N2 were evaluated in vitro in MDCK cells at different time exposure by using TCID50, HA, Real Time PCR and HI assay. The results showed that MOEO could inhibit replication of AVI through the different virus replication phase (P <= 0.05). Also the highest antiviral activity of MOEO was seen when AIV incubated with MOEO before cell infection. The TCID50/ml was reduced 1.3-2.1, 2.3-2.8, 3.7-4.5 log 10 than control group (5.6 log 10), HAU/50 ul was decreased 85-94, 71.4-94, 71.4-94 % and viral genome copy number/ul was brought down 68-95, 90-100, 89.6-99.9 % at pre-infection, post-infection and simultaneous stage, respectively. Hemagglutination inhibition result showed the MOEO was not able to inhibit agglutination of the chicken red blood cell (cRBC). Replication of the AVI was suppressed by the different concentration of oseltamivir completely or near 100 %. Also oseltamivir showed a synergistic activity with MOEO especially when oseltamivir concentration reduced under 0.005 mg/ml. The chemical composition was examined by GC-MS analysis and Its main constituents were identified as monoterpenaldehydes citral a, citral b. In conclusion, the findings of the study showed that lemon balm essential oil could inhibit influenza virus replication through different replication cycle steps especially throughout the direct interaction with the virus particles. PMID- 27366769 TI - Rotavirus infections in Detroit, USA, a region of low vaccine prevalence. AB - After a sharp drop of rotavirus (RV) infections at Children's Hospital of Michigan, Detroit, USA in 2010 season, we noted an increase in the number of cases during the 2011 season including some RV vaccine (RVV) recipients. This study was conducted to determine the circulating genotypes during 2011 season and whether the increase in RV diarrhea was caused by replacement genotypes. G and P genotypes were determined by RT PCR and nucleotide sequencing of selected strains was performed. The vaccination rate among study patients was 24 %. RV strains from 68 stool samples were genotyped including 18 from vaccinated children and 50 from unvaccinated children. The predominant G genotype was G1 (58.8 %) followed by G9 (17.7 %) and G4 (15.5 %). P[8] was the predominant P genotype (68 %) followed by P[6] (17.6 %) and P[4] (3 %). All G9 strains were associated with P[6]. The most prevalent G-P combination was G1P[8] (56 %), followed by G9P[6] (17.6 %). Similar proportions of RV genotypes were found among vaccinated and unvaccinated children. Our local data suggest that 5 years after the introduction of RVV there has been no genotype replacement. Although a small increase in G9P[6] frequency was noted, G1P[8] remained the predominant strain of RV in our inner city community in the Midwestern USA. PMID- 27366770 TI - Chikungunya: a reemerging infection spreading during 2010 dengue fever outbreak in National Capital Region of India. AB - Chikungunya fever is an important reemerging arbovirus illness, which is transmitted by the same vector as of dengue virus. Many cases of concurrent infections with multiple dengue virus serotypes have been reported in many countries. Also, concurrent infection with Chikungunya virus and dengue virus has been reported in the past in Delhi. Therefore, this study was done to detect Chikungunya IgM antibodies in suspected dengue fever patients. In this study, 1666 serum samples suspected of dengue fever and collected during the outbreak period (August 2010-December 2010) were tested for dengue IgM antibodies, of which 736 tested negative. Of the 736 dengue IgM negative sera, 666 were tested for Chikungunya IgM antibodies. The demographic profile and essential laboratory investigations were recorded. Chikungunya IgM was detected in 9.91 % of the patients. During the post-monsoon period though dengue dominated in numbers, the number of Chikungunya fever cases increased gradually followed by an abrupt decrease with the onset of winter. The Chikungunya IgM positive patients were suffering from fever of more than 5 days duration and had thrombocytopenia. Due to similarity in clinical features and vector transmitting dengue and Chikungunya virus, continuous surveillance of both dengue fever and Chikungunya fever is desirable for better management and epidemiological assessment. PMID- 27366771 TI - Molecular characterization of tospoviruses associated with ringspot disease in bell pepper from different districts of Himachal Pradesh. AB - Bell pepper (Capsicum annuum L.), an important cash crop for the farmers of Himachal Pradesh was found to be affected with tospovirus like disease. An extensive survey was conducted in the bell pepper grown areas in the five districts of Himachal Pradesh to identify and characterize the causative agent. Hence, 60 symptomatic bell pepper plants exhibiting characteristics symptoms were collected from Solan, Sirmaur, Hamirpur, Kangra and Bilaspur districts. Out of 60 samples, 53 samples were found to be positive by DAS-ELISA with tospovirus group specific antiserum. To confirm the presence of tospovirus, DAC-ELISA was performed using GBNV/CaCV polyclonal antiserum and DAS-ELISA with two monoclonal antibodies i.e. TSWV, GRSV. All the 53 samples were found negative for TSWV and GRSV and positive for GBNV/CaCV. Further, eleven infected isolates from both poly house and open field conditions were selected for characterization at molecular level. RT-PCR was performed with N gene specific primers for TSWV, GBNV and CaCV. The eleven samples selected for molecular identification were further found to be negative for TSWV and positive for CaCV using RT-PCR. One of the samples from district Sirmaur was found to be positive for mixed infection of GBNV and CaCV. N gene phylogenetic analysis of CaCV/GBNV provided important information about the movement and evolution of tospoviruses in Himachal Pradesh. PMID- 27366772 TI - Partial biological and molecular characterization of a Cucumber mosaic virus isolate naturally infecting Cucumis melo in Iran. AB - Melon seedlings showing systemic chlorotic spots and mosaic symptoms were collected in central part of Iran, and a virus was isolated from diseased plants by mechanical inoculation. The virus systemically infected the most inoculated test plants by inducing mosaic symptoms, while, in the members of Fabaceae family and Chenopodium quinoa induced local lesions. Agar gel diffusion test using a polyclonal antiserum against a squash Cucumber mosaic virus (CMV) isolate showed the presence of CMV in the mechanically inoculated plants (designated CMV-Me). The virus was purified by polyethylene glycol precipitation and differential centrifugation. A polyclonal antiserum was produced against the virus that reacted specifically with virus antigen in ELISA and agar gel diffusion tests. The virus was molecularly characterized by PCR amplification of the full length of the coat protein gene using cucumovirus genus specific primer pair CPTALL 3/CPTALL-5 and sequence analysis of the resulting product. No RNA satellite was detected using the primer pair CMVsat3H/sat5T7P. Phylogenetic analysis based on the coat protein amino acid sequences showed that CMV-Me belongs to Subgroup IB. These results may be helpful in melon breeding programs, focusing on plant resistance to plant viruses including CMV. PMID- 27366773 TI - Occurrence and identification of contagious ecthyma in blackbuck. AB - A carcass of male free ranging adult blackbuck (Antilope cervicapra) was presented for necropsy examination exhibiting thick confluent nodular skin lesions around the mouth and the dry scaly crusts/fissures on the skin of abdomen, thigh and shoulder with subcutaneous haemorrhages. The skin sample around mouth was found positive for orf virus (ORFV) identified by counterimmunoelectrophoresis and PCR. Histopathology of the mouth skin revealed the hyperkeratinization, epidermal sloughing and epithelial hyperplasia showing acanthosis with rete ridges and few eosinophilic intracytoplasmic inclusion bodies in keratinocytes. Further, comparative B2L gene sequence analysis revealed that the virus isolate from blackbuck had shown 97.8-99.6 and 97.6-99.5 % identity at nucleotide and amino acid levels respectively with Indian isolates and maximum identity with ORFV 79/04, an isolate from India. Phylogenetic analysis based on B2L gene also revealed the same evolutionary relationship that it is closely related to Indian isolates. This seems to be the first report of orf in blackbuck from Indian subcontinent. PMID- 27366774 TI - Phylogenetic analysis of Newcastle disease virus isolates occurring in India during 1989-2013. AB - The study details characterization of Newcastle disease virus (NDV) isolates recovered from commercial poultry flocks (chicken) and wild birds (crane) of India during the time period from 1989 to 2013. Phylogenetic analysis revealed that most of the NDV isolates belongs to class II, genotype XIIIa and a chicken isolate (108/BAREILLY/AD-IVRI/91) was of genotype VI, where it showed diversity of 3 % from the other viruses belonging to same genotype. Another chicken isolate (75/RAMPUR/AD-IVRI/89) grouped in genotype III and showed 4 % diversity with viruses of genotype III. The crane origin NDV identified as of genotype II corresponding to the vaccine virus. This appears to be the first report about existence of genotype XIIIa and its ancestral viruses are circulating in India for the last two decades in different species of birds. Furthermore, genetically distinct viruses belonging to genotypes II, III and VI are also circulating in India. PMID- 27366775 TI - First report of association of potato virus X and potato virus Y and 'Candidatus Phytoplasma trifolii' in brinjal in India. AB - Symptoms of little leaf, leaf chlorosis and leaf malformations with mosaic mottling symptoms were observed in two brinjal varieties (Pusa Shyamla and Pusa Purple Cluster) in fields of IARI, New Delhi, India during 2014-2015. Electron microscopy, PCR and sequence analysis first time provided evidence of association of Candidatus Phytoplasma trifolii with potato virus X and potato virus Y in brinjal in India. PMID- 27366776 TI - Orf virus infection in human ecthyma contagiosum: a report of two cases in the West of Iran. AB - Ecthyma contagiosum is caused by the orf virus, a member of the genus Parapoxvirus in the family Poxviridae. Humans acquire the infection from contact with infected or recently vaccinated animals in conjunction with skin trauma. In this study, we report two cases of orf infection in two women who had contact with animals. Diagnosis was based, apart from the clinical signs, on histological examination, virus isolation using fetal bovine esophagus cells, electron microscopy and PCR. PMID- 27366778 TI - Data on human neutrophil activation induced by pepducins with amino acid sequences derived from beta2AR and CXCR4. AB - The data described here is related to the research article titled (Gabl et al., 2016) [1]. Pepducins with peptide sequence derived from one of the intracellular domains of a given G-protein coupled receptor (GPCR) can either activate or inhibit cell functions. Here we include data on human neutrophil function induced by pepducins derived from beta2AR (ICL3-8) and CXCR4 (ATI-2341), respectively. ICL3-8 exerts neither direct activating effect on the NADPH-oxidase as measured by superoxide release nor inhibitory effect on FPR signaling. ATI-2341 dose dependently triggers neutrophil activation and these cells were subsequently desensitized in their response to FPR2 specific agonists F2Pal10 and WKYMVM. Moreover, the ATI-2341 response is inhibited by PBP10 and the peptidomimetic Pam (Lys-betaNSpe)6-NH2 (both are FPR2 specific inhibitors), but not to the FPR1 specific inhibitor cyclosporine H. PMID- 27366777 TI - Perfusion magnetic resonance imaging provides additional information as compared to anatomical imaging for decision-making in vestibular schwannoma. AB - OBJECTIVE: The added value of perfusion MRI for decision-making in vestibular schwannoma (VS) patients is unknown. MRI offers two perfusion methods: the first employing contrast agent (dynamic susceptibility contrast (DSC)-MRI) that provides information on cerebral blood volume (CBV) and cerebral blood flow (CBF), the second by magnetic labeling of blood (arterial spin labeling (ASL) MRI), providing CBF-images. The goal of the current study is to investigate whether DSC and ASL perfusion MRI provides complimentary information to current anatomical imaging in treatment selection process of VS. METHODS: Nine patients with growing VS with extrameatal diameter >9 mm were included (>2 mm/year and 20% volume expansion/year) and one patient with 23 mm extrameatal VS without growth. DSC and ASL perfusion MRI were obtained on 3 T MRI. Perfusion in VS was scored as hyperintense, hypointense or isointense compared to the contralateral region. RESULTS: Seven patients showed hyperintense signal on DSC and ASL sequences. Three patients showed iso- or hypointense signal on at least one perfusion map (1 patient hypointense on both DSC-MRI and ASL; 1 patient isointense on DSC-CBF; 1 patient isointense on ASL). All patients showed enhancement on post-contrast T1 anatomical scan. CONCLUSION: Perfusion MR provides additional information compared to anatomical imaging for decision-making in VS. PMID- 27366779 TI - Comparative testis proteome dataset between cattleyak and yak. AB - Cattleyak are hybrid between cattle and yak, which exhibit equivalent adaptability on the Qinghai-Tibetan Plateau as yak and much higher capability in economic traits. However, the F1 males of cattleyak are infertile due to spermatogenic arrest and this greatly restricts the effective utilization of this hybrid. In this data article, differentially expressed proteins (DEPs) were identified from testis proteome of cattleyak and yak using high-performance liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS). All the DEPs were subjected to functional classification by Gene Ontology (GO) analysis and gene-pathway annotation by Kyoto Encyclopedia of Genes and Genomes (KEGG). The comparative testis proteome dataset here can shed new light on the molecular characteristics of male infertility of cattleyak on proteome level, "Comparative iTRAQ proteomics revealed proteins associated with spermatogenic arrest of cattleyak" [1]. PMID- 27366780 TI - Data of rational process optimization for the production of a full IgG and its Fab fragment from hybridoma cells. AB - This data article focuses on the production of monoclonal antibodies (mAb) and their fragments Fab and F(ab')2. Here, we present the data of an optimization protocol to improve the product yield of a hybridoma cell process using a Design of Experiment (DoE) strategy. Furthermore, the data of the evaluated conditions were used to test feeding strategies in shake flasks. They were verified in controlled 2 L fed-batch bioreactor processes. Supplementing the culture medium with human insulin-like growth factor-I (IGF-I) and Pluronic F-68, as well as a nutrient rich additive for fed-batch, resulted in improved cell growth correlating with a 7 day elongated process time and a 4.5 fold higher product titer. Finally, a rapid Fab generation protocol and the respective data are presented using different papain digestion and a camelid anti-kappa light chain VHH affinity ligand. PMID- 27366781 TI - Data set of optimal parameters for colorimetric red assay of epoxide hydrolase activity. AB - The data presented in this article are related to the research article entitled "Epoxide hydrolase of Trichoderma reesei: Biochemical properties and conformational characterization" [1]. Epoxide hydrolases (EHs) are enzymes that catalyze the hydrolysis of epoxides to the corresponding vicinal diols. This article describes the optimal parameters for the colorimetric red assay to determine the enzymatic activity, with an emphasis on the characterization of the kinetic parameters, pH optimum and thermal stability of this enzyme. The effects of reagents that are not resistant to oxidation by sodium periodate on the reactions can generate false positives and interfere with the final results of the red assay. PMID- 27366782 TI - Data on synthesis and characterization of chitosan nanoparticles for in vivo delivery of siRNA-Npr3: Targeting NPR-C expression in the heart. AB - This data article contains the data related to the research article 'Transient silencing of Npr3 gene expression improved the circulatory levels of atrial natriuretic peptides and attenuated beta-adrenoceptor activation-induced cardiac hypertrophic growth in experimental rats' (Venkatesan et al., 2016 [1]). The siRNA-Npr3 loaded chitosan nanoparticles were synthesized using ionotropic gelation method, where the positive charge of the chitosan interacts with the negative charge of STPP and siRNA-Npr3. The physicochemical properties of the synthesized siRNA-Npr3 loaded chitosan nanoparticles were studied by dynamic light scattering, FE-SEM and HR-TEM analysis. In addition, the loading efficiency and stability of the nanoparticles were also studied. Further, the gene silencing efficacy, hemocompatibility and biocompatibility were studied using Wistar rats (in vivo), isolated red blood cells and H9c2 cardiomyoblast cells, respectively. PMID- 27366783 TI - Data set for diet specific differential gene expression analysis in three Spodoptera moths. AB - Examination of closely related species pairs is suggested for evolutionary comparisons of different degrees of polyphagy, which we did here with three taxa of lepidopteran herbivores, Spodoptera spp (S. littoralis, S. frugiperda maize (C) and rice (R) strains) for a RNAseq analysis of the midguts from the 3rd instar insect larvae for differential metabolic responses after feeding on pinto bean based artificial diet vs maize leaves. Paired-end (2*100 bp) Illumina HiSeq2500 sequencing resulted in a total of 24, 23, 24, and 21 million reads for the SF-C-Maize, SF-C-Pinto, SF-R-Maize, SF-R Pinto, and a total of 35 and 36 million reads for the SL-Maize and SL-Pinto samples, respectively. After quality control measures, a total of 62.2 million reads from SL and 71.7 million reads from SF were used for transcriptome assembly (TA). The resulting final de novo reference TA (backbone) for the SF taxa contained 37,985 contigs with a N50 contig size of 1030 bp and a maximum contig length of 17,093 bp, while for SL, 28,329 contigs were generated with a N50 contig size of 1980 bp and a maximum contig length of 18,267 bp. The data presented herein contains supporting information related to our research article Roy et al. (2016) http://dx.doi.org/10.1016/j.ibmb.2016.02.006[1]. PMID- 27366784 TI - Comprehensive dataset of the medicinal plants used by a Tashelhit speaking community in the High Atlas, Morocco. AB - This dataset describes medicinal plants used in a poorly studied area of Morocco: the High Atlas mountains, inhabited by Ishelhin people, the southern Moroccan Amazigh (Berber) ethnic group, "An ethnomedicinal survey of a Tashelhit-speaking community in the High Atlas, Morocco" (Teixidor-Toneu et al., 2016) [1]. It includes a comprehensive list of the plants used in the commune, as well as details on the plant voucher specimens collected and a glossary of Tashelhit terminology relevant to the study. To collect the data, semi-structured and structured interviews were carried out, as well as focus group discussions. Free prior informed consent was obtained for all interactions. A hundred and six adults were interviewed and 2084 use reports were collected; a hundred fifty-one vernacular names corresponding to 159 botanical species were found. PMID- 27366785 TI - Dataset of Arabidopsis plants that overexpress FT driven by a meristem-specific KNAT1 promoter. AB - In this dataset we integrated figures comparing leaf number and rosette diameter in three Arabidopsis FT overexpressor lines (AtFTOE) driven by KNAT1 promoter, "A member of the KNOTTED class of homeodomain proteins encoded by the STM gene of Arabidopsis" [5], vs Wild Type (WT) Arabidopsis plats. Also, presented in the tables are some transcriptomic data obtained by RNA-seq Illumina HiSeq from rosette leaves of Arabidopsis plants of AtFTOE 2.1 line vs WT with accession numbers SRR2094583 and SRR2094587 for AtFTOE replicates 1-3 and AtWT for control replicates 1-2 respectively. Raw data of paired-end sequences are located in the public repository of the National Center for Biotechnology Information of the National Library of Medicine, National Institutes of Health, United States of America, Bethesda, MD, USA as Sequence Read Archive (SRA). Performed analyses of differential expression genes are visualized by Mapman and presented in figures. "Transcriptomic analysis of Arabidopsis overexpressing flowering locus T driven by a meristem-specific promoter that induces early flowering" [2], described the interpretation and discussion of the obtained data. PMID- 27366786 TI - Pincer nails in a patient with systemic lupus erythematosus and lupus nephritis: A case report. PMID- 27366787 TI - The Challenges of Nursing Students in the Clinical Learning Environment: A Qualitative Study. AB - Background/Aim. Clinical learning is a main part of nursing education. Students' exposure to clinical learning environment is one of the most important factors affecting the teaching-learning process in clinical settings. Identifying challenges of nursing students in the clinical learning environment could improve training and enhance the quality of its planning and promotion of the students. We aimed to explore Iranian nursing students' challenges in the clinical learning environment. Materials and Methods. This is a qualitative study using the content analysis approach. The participants consisted of seventeen nursing students and three nursing instructors. The participants were selected through purposive sampling method and attended semistructured interviews and focus groups. Results. Three themes emerged after data analysis, including ineffective communications, inadequate readiness, and emotional reactions. Conclusion. Nursing students in Iran are faced with many challenges in the clinical learning environment. All challenges identified in this study affected the students' learning in clinical setting. Therefore, we recommend that the instructors prepare students with a specific focus on their communication and psychological needs. PMID- 27366788 TI - Association between Reactive Attachment Disorder/Disinhibited Social Engagement Disorder and Emerging Personality Disorder: A Feasibility Study. AB - A systematic review of reactive attachment disorder (RAD)/disinhibited social engagement disorder (DSED) in adolescence highlighted that young people with the disorder had indiscriminate friendliness with difficulties in establishing and maintaining stable relationships. Most reported experiences of rejection. We were struck by similarities between the above and features of emergence of personality disorders (EPD). This feasibility study aimed to determine best ways of recruiting and retaining vulnerable young people and the proportion of participants with RAD/DSED who might have emerging borderline personality disorder (EBPD). Participants were referred to the study by their treating clinicians from local mental health teams. Results showed strong association between RAD/DSED and EBPD. Participant characteristics showed high levels of out of home placements, early termination of school careers, suicide attempts, quasipsychotic symptoms, and multiagency involvements. They experienced the project as an opportunity to talk about relationships and reported that they would like more of this in usual clinical contacts. They all agreed to be contacted for future studies. Previous studies have shown that early detection and treatment of emergent personality traits can alter trajectory. Future research will continue to explore these trajectories, explore detection of vulnerability factors, and evaluate interventions. PMID- 27366789 TI - Recent Trends and Techniques in Computing Information Intelligence. PMID- 27366790 TI - Minimally Invasive Treatment of Infrabony Periodontal Defects Using Dual Wavelength Laser Therapy. AB - Introduction. Surgical management of infrabony defects is an invasive procedure, frequently requiring the use of adjunctive material such as grafts or biologics, which is time-consuming and associated with expense and morbidity to the patient. Lasers in periodontal regeneration have been reported in the literature, with each wavelength having potential benefits through different laser-tissue interactions. The purpose of this case series was to assess the efficacy of a new dual-wavelength protocol in the management of infrabony defects. Materials and Methods. 32 defects (one in each patient) were treated using ultrasonic debridement, followed by flapless application of Erbium, Chromium:Yttrium, Scandium, Gallium, Garnet (Er,Cr:YSGG) laser (wavelength 2780 nm), and final application of diode laser (wavelength 940 nm). Pocket depths (PD) were measured after 6 months and repeat radiographs taken after one year. Results. The mean baseline PD was 8.8 mm (range 6-15 mm) and 6 months later was 2.4 mm (range 2-4 mm), with mean PD reduction being 6.4 +/- 1.7 mm (range 3-12 mm). There was a significant gain in relative linear bone height (apical extent of bone), with mean percentage bone fill of 39.7 +/- 41.2% and 53% of sites showing at least 40% infill of bone. Conclusion. The results compare favourably with traditional surgery and require further validation through randomised clinical controlled trials. PMID- 27366792 TI - Kidney alpha-Intercalated Cells, NGAL and Urinary Tract Infection. AB - It is well known that kidney alpha-intercalated cells can acidify the urine and acidified urine can inhibit bacterial growth and other urinary organisms. However, regulation of acid-base balance rather than a dedicated function in preventing urinary tract infection has been assigned to alpha-intercalated cells. A series of studies, culminated by the publication of a paper (J Clin Invest. 2014 Jul 1;124(7):2963-76) from Dr. Barasch's lab unearthed a novel mechanism by which alpha-intercalated cells function in the innate immune defense of urinary tract infection. This mechanism involves production and release of neutrophil gelatinase-associated lipocalin by alpha-intercalated cells to chelate the siderophore containing host iron to achieve bacteriostasis. PMID- 27366791 TI - Cardiac myosin-Th17 responses promote heart failure in human myocarditis. AB - In human myocarditis and its sequela dilated cardiomyopathy (DCM), the mechanisms and immune phenotype governing disease and subsequent heart failure are not known. Here, we identified a Th17 cell immunophenotype of human myocarditis/DCM with elevated CD4+IL17+ T cells and Th17-promoting cytokines IL-6, TGF-beta, and IL-23 as well as GM-CSF-secreting CD4+ T cells. The Th17 phenotype was linked with the effects of cardiac myosin on CD14+ monocytes, TLR2, and heart failure. Persistent heart failure was associated with high percentages of IL-17-producing T cells and IL-17-promoting cytokines, and the myocarditis/DCM phenotype included significantly low percentages of FOXP3+ Tregs, which may contribute to disease severity. We demonstrate a potentially novel mechanism in human myocarditis/DCM in which TLR2 peptide ligands from human cardiac myosin stimulated exaggerated Th17-related cytokines including TGF-beta, IL-6, and IL-23 from myocarditic CD14+ monocytes in vitro, and an anti-TLR2 antibody abrogated the cytokine response. Our translational study explains how an immune phenotype may be initiated by cardiac myosin TLR ligand stimulation of monocytes to generate Th17-promoting cytokines and development of pathogenic Th17 cells in human myocarditis and heart failure, and provides a rationale for targeting IL-17A as a therapeutic option. PMID- 27366793 TI - A turn-on fluorescence chemosensor based on a tripodal amine [tris(pyrrolyl-alpha methyl)amine]-rhodamine conjugate for the selective detection of zinc ions. AB - A novel tetradendate ligand derived from a tris(pyrrolyl-alpha-methyl)amine (H3tpa) and rhodamine-based conjugate (PR) has been designed for use as a sensor, synthesized and characterized spectroscopically. PR {(tris(5-rhodamineiminopyrrol 2-ylmethyl)amine)} serves as a selective colorimetric as well as a fluorescent chemosensor for Zn(2+) in acetonitrile/water (1 : 1, v/v). In the presence of Zn(2+), PR exhibited obvious absorption (558 nm) and emission (577 nm) peaks whose intensity increased along with increasing Zn(2+) concentrations. Titration experiments revealed that a large excess of Zn(2+) was required to saturate the absorption (lambdamax) and emission intensities. Upon the addition of 1000 equivalents of Zn(2+), the fluorescence intensity of the PR underwent an ~500 fold increase (Phif = 0.34) with the emission maximum at 580 nm. These kinetics studies demonstrated that the absorption and emission changes were proportional to the Zn(2+) concentration. The color of the solution changed from colorless to a dark pink color. The fluorescence of the PR-Zn(2+) complex can be reversibly restored by using ammonium water or by heating. Competitive ion tests revealed that the intensity of PR-Zn(2+) was not suppressed by excess amounts of other metal ions. The counter anions did not exert obvious influences on the absorption and emission profiles. (1)H-NMR and FT-IR spectroscopic investigations of PR and PR-Zn(2+) revealed that the pyrrole motifs, -C[double bond, length as m-dash]N- groups and spirolactam of rhodamine B are capable of coordinating cation guest species. Because each arm of the tripodal ligand tautomerizes independently, only moderate fluorescence enhancement could be seen until all three -C[double bond, length as m-dash]N- groups were coordinated by zinc, which may be due to the spirolactam ring opening mechanism of the rhodamine unit. Once all three C[double bond, length as m-dash]N- groups were locked by coordinating with excess of Zn(2+), the isomerization was arrested, and PR exhibited highly enhanced fluorescence. In addition, energy optimized structures of PR were found to be cage-like by Gaussian 09, further supporting that it can access a large excess of Zn(2+). Intriguingly, imaging of HeLa cells by using a confocal microscope revealed that this PR probe could be used for biological applications. PMID- 27366794 TI - Modelling spin Hamiltonian parameters of molecular nanomagnets. AB - Molecular nanomagnets encompass a wide range of coordination complexes possessing several potential applications. A formidable challenge in realizing these potential applications lies in controlling the magnetic properties of these clusters. Microscopic spin Hamiltonian (SH) parameters describe the magnetic properties of these clusters, and viable ways to control these SH parameters are highly desirable. Computational tools play a proactive role in this area, where SH parameters such as isotropic exchange interaction (J), anisotropic exchange interaction (Jx, Jy, Jz), double exchange interaction (B), zero-field splitting parameters (D, E) and g-tensors can be computed reliably using X-ray structures. In this feature article, we have attempted to provide a holistic view of the modelling of these SH parameters of molecular magnets. The determination of J includes various class of molecules, from di- and polynuclear Mn complexes to the {3d-Gd}, {Gd-Gd} and {Gd-2p} class of complexes. The estimation of anisotropic exchange coupling includes the exchange between an isotropic metal ion and an orbitally degenerate 3d/4d/5d metal ion. The double-exchange section contains some illustrative examples of mixed valance systems, and the section on the estimation of zfs parameters covers some mononuclear transition metal complexes possessing very large axial zfs parameters. The section on the computation of g anisotropy exclusively covers studies on mononuclear Dy(III) and Er(III) single ion magnets. The examples depicted in this article clearly illustrate that computational tools not only aid in interpreting and rationalizing the observed magnetic properties but possess the potential to predict new generation MNMs. PMID- 27366795 TI - Mechanistic insights into light-driven graphene-induced peroxide decomposition: radical generation and disproportionation. AB - Interaction between adsorbed t-butyl peroxybenzoate and photoexcited graphene rendered trapped phenyl and t-butoxy radicals. Post-irradiation thermal desorption showed benzene, t-butanol, and isobutylene oxide as the end products. The required hydrogen atoms were obtained via the radical disproportionation. Graphene enabled radical species to be captured and their on-surface chemistry to be revealed. PMID- 27366796 TI - Light-, pH- and thermal-responsive hydrogels with the triple-shape memory effect. AB - Light-, pH- and thermal-responsive hydrogels were prepared by introducing dansyl aggregations and azo-cyclodextrin inclusion complexes as switches. The resulting material showed dual shape memory behavior in response to light, pH or temperature, respectively, and exhibits the triple-shape memory effect in response to light and pH sequentially. PMID- 27366797 TI - Enteric Fever and Invasive Nontyphoidal Salmonellosis--9th International Conference on Typhoid and Invasive NTS Disease, Bali, Indonesia, April 30-May 3, 2015. PMID- 27366798 TI - 100 years of images. PMID- 27366799 TI - CardioPulse: Reducing the number of inappropriate invasive procedures in cardiology utilizing an online regulatory system. PMID- 27366800 TI - CardioPulse: Martyn Thomas discusses moving from interventional cardiology to industry. PMID- 27366801 TI - CardioPulse: Mentoring young physician-scientists. A Position and Practice Guide by a Young MD/PhD and a Department Head. PMID- 27366802 TI - Average price paid for 162 common medical services by state. Ranked by the ratio of state average to the national average. PMID- 27366804 TI - Biggest healthcare M&A deals of Q1 2016. Ranked by deal value. PMID- 27366803 TI - Customizing transitional care for North Carolina Medicaid patients. PMID- 27366805 TI - 10 steps to improve security of mobile technology. PMID- 27366806 TI - Industry ICD-10 Summit recommendations echo MGMA perspective. PMID- 27366807 TI - My journey to becoming a RD. PMID- 27366809 TI - EFT and virtual credit card payments: 10 tips for your practice. PMID- 27366808 TI - HIPAA/Omnibus patient 'self-pay' restriction requirements: Q&A. PMID- 27366810 TI - Tracking ICD-10: A guide to internal assessments. PMID- 27366811 TI - Culinary medicine: The new 'in' thing? PMID- 27366812 TI - What's your staff holiday schedule? PMID- 27366813 TI - Growing Algae Alter Spectroscopic Characteristics and Chlorine Reactivity of Dissolved Organic Matter from Thermally-Altered Forest Litters. AB - Previous studies demonstrated that wildfires alter spectroscopic characteristics of terrestrial dissolved organic matter (DOM) and increase specific disinfection byproduct formation potential (SDBP-FP). However, it is unclear whether characteristics of thermally altered DOM (TA-DOM) are altered by biogeochemical processes (e.g., transformed by growing algae) before entering water treatment facilities. The freshwater green algae Pseudokirchneriella subcapitata and blue green algae Microcystis aeruginosa were separately incubated in the mixture of cultural medium and pine (Pinus palustris) litter-derived TA-DOMs (50 degrees C, 250 degrees C, and 400 degrees C) over 7 days to demonstrate the effects of algal growth on alterations in SDBP-FP. TA-DOM optical characteristics and SDBP FP were quantified by absorption and fluorescence spectroscopy and chlorination based DBP-FP experiments. After the inoculation with P. subcapitata, TA-DOM aromaticity (indicated by SUVA254) increased from 1.19 to 1.90 L/mg/m for 50 degrees C-extract but decreased from 4.95 to 3.75 L/mg/m for 400 degrees C extract. The fraction of tyrosine-like components decreased from 25.9 to 9.3% for 50 degrees C-extract but increased from 0.9 to 1.3% for 400 degrees C-extract. Same patterns were also observed for M. aeruginosa. Growing algae generally increased chlorine reactivities and formations of trihalomethanes, haloacetonitriles, chloral hydrate, and haloketones. Our data suggest that the biodegradable dissolved organic carbon in TA-DOM decreases as fire intensity (i.e., temperature) increases. Postfire algal blooms can increase chlorine reactivity of fire-affected terrestrial DOM for DBP formation. PMID- 27366814 TI - Protective effect by maximal isometric contractions against maximal eccentric exercise-induced muscle damage of the knee extensors. AB - This study investigated whether maximal voluntary isometric contractions (MVIC) performed before maximal eccentric contractions (MaxEC) would attenuate muscle damage of the knee extensors. Untrained men were placed to an experimental group that performed 6 sets of 10 MVIC at 90 degrees knee flexion 2 weeks before 6 sets of 10 MaxEC or a control group that performed MaxEC only (n = 13/group). Changes in muscle damage markers were assessed before to 5 days after each exercise. Small but significant changes in maximal voluntary concentric contraction torque, range of motion (ROM) and plasma creatine kinase (CK) activity were evident at immediately to 2 days post-MVIC (p < 0.05), but other variables (e.g. thigh girth, myoglobin concentration, B-mode echo intensity) did not change significantly. Changes in all variables after MaxEC were smaller (p < 0.05) by 45% (soreness)-67% (CK) for the experimental than the control group. These results suggest that MVIC conferred potent protective effect against MaxEC induced muscle damage. PMID- 27366815 TI - Mitochondria as a target for neuroprotection: implications for Alzheimer's disease. AB - INTRODUCTION: Alzheimer's disease (AD), the most common form of dementia, is marked by progressive loss of memory and impairment of cognitive ability. Despite decades of intensive research and scientific advances, the intricate pathogenic mechanisms of AD are still not fully understood and, consequently, an effective treatment is yet to be developed. As widely accepted, the alterations of mitochondrial function are actively engaged in a plethora of neurodegenerative diseases, including AD. With growing interest in the mitochondria as a potential target for understanding AD, it has even been hypothesized that deficits in these organelles may be at the heart of the progression of AD itself. Areas covered: The purpose of this review is to summarize relevant studies that suggest a role for mitochondrial (dys)function in AD and to provide a survey on latest developments regarding AD-related mitochondrial therapeutics. Expert commentary: As outlined in a plethora of studies, there is no doubt that mitochondria play a major role in several stages of AD progression. Even though more in-depth studies are needed before pharmaceutical industry can apply such knowledge to human medicine, the continuous advances in AD research field will certainly facilitate and accelerate the development of more effective preventive or therapeutic strategies to fight this devastating disease. PMID- 27366817 TI - Comparison of stepwise vs single-step advancement with the Functional Mandibular Advancer in Class II division 1 treatment. AB - OBJECTIVE: To compare two groups of subjects at the peak of the pubertal growth period treated with the Functional Mandibular Advancer (FMA; Forestadent, Pforzheim, Germany) appliance using either single-step or stepwise mandibular advancement. MATERIALS AND METHODS: This study was conducted on 34 Class II division 1 malocclusion subjects at or just before the peak phase of pubertal growth as assessed by hand-wrist radiographs. Subjects were assigned to two groups of mandibular advancement, using matched randomization. Both groups were treated with the FMA. While the mandible was advanced to a super Class I molar relation in the single-step advancement group (SSG), patients in the stepwise mandibular advancement group (SWG) had a 4-mm initial bite advancement and subsequent 2-mm advancements at bimonthly intervals. The material consisted of lateral cephalograms taken before treatment and after 10 months of FMA treatment. Data were analyzed by means paired t-tests and an independent t-test. RESULTS: There were statistically significant changes in SNB, Pg horizontal, ANB, Co-Gn, and Co-Go measurements in both groups (P < .001); these changes were greater in the SWG with the exception of Co-Go (P < .05). While significant differences were found in U1-SN, IMPA, L6 horizontal, overjet, and overbite appraisals in each group (P < .001), these changes were comparable (P > .05). CONCLUSION: Because of the higher rates of sagittal mandibular skeletal changes, FMA using stepwise advancement of the mandible might be the appliance of choice for treating Class II division 1 malocclusions. PMID- 27366816 TI - Three-dimensional evaluation of social smile symmetry. AB - OBJECTIVE: To evaluate the social smile symmetry using three-dimensional (3D) stereophotogrammetric images. MATERIALS AND METHODS: The study was conducted with 3D facial images of 30 individuals (age range 13-25 years). The rest position was considered as the reference image and the social smile image was aligned on this image using the best-fit alignment method. The spatial differences between the same points established on both images using 3D analyses were determined for right and left points in X, Y, and Z planes. RESULTS: The highest difference related to spatial distance in right and left points was -0.56 mm (95% confidence interval [CI], -1.19, 0.06 mm) between right and left commissure (Com) points. The difference was not significant, and the Bland-Altman upper and lower limits were -3.85 mm and 2.71 mm, respectively. The highest difference for the transversal plane was found in Com points, similarly to the spatial distance (mean: 0.50 mm, 95% CI, -2.62, 1.02 mm). The differences between the changes in the left and right points in the Y and Z plane were not significant (P > .05). CONCLUSIONS: The social smile was observed to show asymmetry in varying amounts in the different directions. Asymmetry increases in some cases, specifically for the corners of the mouth. PMID- 27366818 TI - Reactions of Persistent Carbenes with Hydrogen-Terminated Silicon Surfaces. AB - Surface passivation has enabled the development of silicon-based solar cells and microelectronics. However, a number of emerging applications require a paradigm shift from passivation to functionalization, wherein surface functionality is installed proximal to the silicon surface. To address this need, we report here the use of persistent aminocarbenes to functionalize hydrogen-terminated silicon surfaces via Si-H insertion reactions. Through the use of model compounds (H Si(TMS)3 and H-Si(OTMS)3), nanoparticles (H-SiNPs), and planar Si(111) wafers (H Si(111)), we demonstrate that among different classes of persistent carbenes, the more electrophilic and nucleophilic ones, in particular, a cyclic (alkyl)(amino)carbene (CAAC) and an acyclic diaminocarbene (ADAC), are able to undergo insertion into Si-H bonds at the silicon surface, forming persistent C-Si linkages and simultaneously installing amine or aminal functionality in proximity to the surface. The CAAC (6) is particularly notable for its clean insertion reactivity under mild conditions that produces monolayers with 21 +/- 3% coverage of Si(111) atop sites, commensurate with the expected maximum of ~20%. Atomic force and transmission electron microscopy, nuclear magnetic resonance, X-ray photoelectron, and infrared spectroscopy, and time-of-flight secondary ion mass spectrometry provided evidence for the surface Si-H insertion process. Furthermore, computational studies shed light on the reaction energetics and indicated that CAAC 6 should be particularly effective at binding to silicon dihydride, trihydride, and coupled monohyride motifs, as well as oxidized surface sites. Our results pave the way for the further development of persistent carbenes as universal ligands for silicon and potentially other nonmetallic substrates. PMID- 27366819 TI - Portable, Constriction-Expansion Blood Plasma Separation and Polymerization-Based Malaria Detection. AB - A portable, microfluidic blood plasma separation device is presented featuring a constriction-expansion design, which produces 100.0% purity for undiluted blood at 9% yield. This level of purity represents an improvement of at least 1 order of magnitude with increased yield compared to that achieved previously using passive separation. The system features high flow rates, 5-30 MUL/min plasma collection, with minimal clogging and biofouling. The simple, portable blood plasma separation design is hand-driven and can easily be incorporated with microfluidic or laboratory scale diagnostic assays. The separation system was applied to a paper-based diagnostic test for malaria that produced an amplified color change in the presence of Plasmodium falciparum histidine-rich protein 2 at a concentration well below clinical relevancy for undiluted whole blood. PMID- 27366820 TI - Intraoperative graft verification in coronary surgery. AB - Transit-time flow measurement (TTFM) is a reliable method to check the graft function intraoperatively in coronary surgery. The given parameters are: Mean Graft Flow (MGF); Pulsatility Index (PI) and Insufficiency Ratio (%BF). Some cutoffs of these parameters have been identified as predictors for unfair 1-y clinical outcome: mean graft flow (MGF) less than 20 ml/min and high pulsatility index greater than 5. Other cutoffs have been found as related to postoperative angiography: MGF 15 ml/min or less and pulsatility index at least 3 (sensitivity 94%; specificity 61%); MGF less than 15 ml/min and pulsatility index greater than 3 for left coronary artery or pulsatility index greater than 5 for right coronary artery (sensitivity 96%; specificity 77%); MGF 15 ml/min or less and pulsatility index at least 5.1 left coronary artery (sensitivity 98%; specificity 26%). Hence, with the need to improve the diagnostic accuracy of TTFM, high-resolution epicardic coronary ultrasound module has been added to graft flow evaluation providing 2D ultrasound imaging (either in short-axis or long-axis) and color flow mapping, allowing an accurate morphological evaluation of body graft and anastomosis. An intraoperative method aimed to verify coronary grafts should be easy to handle, not time consuming, minimally invasive, easily meaningful and relatively cheap; in addition, it should offer objective parameters more than qualitative criteria. We herein report the results of our experience with intraoperative graft verification with TTFM and high-resolution imaging along with a systematic review of the literature in this field with the aim to provide a road map to be followed. PMID- 27366821 TI - The Nature of the Noncovalent Interactions between Benzene and C60 Fullerene. AB - Noncovalent interactions between aromatic compounds and fullerenes have received considerable attention in various fields of science and technology. Employing benzene (C6H6) and C60 fullerene as model molecules, we theoretically explored in the present study the nature of this kind of noncovalent interaction. Our results clearly show that the pi...pi stacking configurations of the complex C6H6...C60 are more strongly bound than in the C-H...pi analogues, and the C-H...pi interactions in the C-H...pi configurations of C6H6...C60 are not of the hydrogen bonds. According to symmetry adapted perturbation theory analyses, all of the configurations of C6H6...C60 are dominated by dispersion forces. The percentage of the dispersion components in the overall attractive interactions for the pi...pi stacking configurations is smaller than the percentage of the dispersion components in the overall attractive interactions for the C-H...pi configurations, whereas the percentage of the electrostatic terms in the overall attractive interactions for the pi...pi stacking configurations is larger than the percentage of the electrostatic terms in the overall attractive interactions for the C-H...pi configurations. This is distinctly different from the case of the benzene dimer. PMID- 27366822 TI - Perovskite-Like Polar Lanthanide Formate Frameworks of [NH2NH3][Ln(HCOO)4] (Ln = Tb-Lu and Y): Synthesis, Structures, Magnetism, and Anisotropic Thermal Expansion. AB - A series of isostructural hydrazinium lanthanide (Ln) formate framework compounds of [NH2NH3][Ln(HCOO)4] for Ln3+ ions from Tb3+ to Lu3+ and Y3+ have been successfully prepared by utilizing NH2NH3+. The compounds crystallize in orthorhombic polar space group Pca21, with cell parameters at 180 K of a = 18.2526(7)-18.1048(5) A, b = 6.5815(2)-6.5261(2) A, c = 7.6362(3)-7.5044(2) A, and V = 917.33(6)-886.67(4) A3, showing the effect of lanthanide contraction. The compounds possess polar perovskite-like structures incorporating the hydrazinium cations in the cavities of the NaCl-like framework, in which the Ln3+ ions in a bicapped trigonal prism are connected by anti-anti and syn-anti formate groups. The N-H...Oformate hydrogen-bonding interactions are between the hydrazinium cations and the anionic framework. One anti-anti formate group is frustrated by the competitive N-H...Oformate hydrogen-bonding interactions. It thus twists or flips upon warming, resulting in large anisotropic thermal expansion and negative thermal expansion below 180 K. A comparison with the transition metal and magnesium analogues revealed that the structural compactness, tighter binding of the hydrazinium cation by the framework, and symmetrically better match between the framework and ammonium cation for Ln compounds could inhibit the occurrence of phase transition in the series. The IR spectroscopic, thermal, and magnetic properties are investigated. PMID- 27366823 TI - To Appear in CHEMICAL REVIEWS, Vol. 99, No. 9. PMID- 27366825 TI - Outcomes Disparities between Black and White Populations in the Surgical Management of Glaucoma. AB - African descent is a well-documented risk factor for glaucoma development, progression, and medical and surgical failure. We reviewed the literature for evidence of outcomes disparities between Black and White populations after trabeculectomy, Ex-PRESS shunt, viscocanalostomy, canaloplasy, tube shunt, laser trabeculoplasty, and cyclophotocoagulation. There are reports of decreased surgical success in Black patients after trabeculectomy, Ex-PRESS shunt, tube shunt, and canaloplasty. At this time, there is no strong evidence that any procedure is more effective for intraocular pressure control than standard trabeculectomy for Black patients. Furthermore, there is insufficient evidence to recommend any particular secondary intervention over another, despite differences in inflammation and bleb-dependence. There is a need for randomized, controlled trials to assess race as a risk factor for failure after non-penetrating filtration surgery (NPFS). There is also a need for data on the efficacy of minimally invasive glaucoma surgery (MIGS) in Black populations. PMID- 27366826 TI - Are the effects of IVF on DNA methylation driven by intracytoplasmic sperm injection and male infertility? PMID- 27366827 TI - Integration of calcium and ABA signaling. AB - Abiotic stresses simultaneously trigger an increase in the level of the plant hormone abscisic acid (ABA) and in the concentration of cytosolic calcium. Subsequent signaling cascades convey stomata regulation and transcriptional responses. Increasing evidence points to direct interrelations of both signaling systems on multiple levels of information processing. In this context, protein phosphatases 2Cs of the clade A appear to function as master regulators of both ABA and calcium signaling. In this review, we focus on informative examples for convergence of ABA and calcium signaling on common target proteins and discuss emerging concepts, consequences and open questions about the integration of calcium and ABA signaling. PMID- 27366828 TI - Parents' Experiences and Perceptions when Classifying their Children with Cerebral Palsy: Recommendations for Service Providers. AB - AIMS: This study investigated the experiences and perceptions of parents of children with cerebral palsy (CP) when classifying their children using the Gross Motor Function Classification System (GMFCS), the Manual Ability Classification System (MACS), and the Communication Function Classification System (CFCS). The second aim was to collate parents' recommendations for service providers on how to interact and communicate with families. METHODS: A purposive sample of seven parents participating in the On Track study was recruited. Semi-structured interviews were conducted orally and were audiotaped, transcribed, and coded openly. A descriptive interpretive approach within a pragmatic perspective was used during analysis. RESULTS: Seven themes encompassing parents' experiences and perspectives reflect a process of increased understanding when classifying their children, with perceptions of utility evident throughout this process. Six recommendations for service providers emerged, including making the child a priority and being a dependable resource. CONCLUSIONS: Knowledge of parents' experiences when using the GMFCS, MACS, and CFCS can provide useful insight for service providers collaborating with parents to classify function in children with CP. Using the recommendations from these parents can facilitate family provider collaboration for goal setting and intervention planning. PMID- 27366829 TI - High circulating levels of sICAM-1 and sVCAM-1 in the patients with Hashimoto's thyroiditis. AB - OBJECTIVE: To investigate whether soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels are increased in euthyroid patients with Hashimoto's thyroiditis (HT) and whether they are associated with thyroid autoimmunity and metabolic parameters. DESIGN: Cross-sectional. SUBJECTS AND METHODS: In total, 80 euthyroid patients with HT and 80 age- and body mass index (BMI)-matched control participants were included. Serum sICAM-1, sVCAM-1, free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (anti-TPO), thyroglobulin antibody (anti-TG), fasting blood glucose (FBG), insulin, and lipid levels and homeostasis model assessment for insulin resistance (HOMA-IR) were assessed in all participants. RESULTS: The patients with HT had significantly higher levels of sICAM-1 and sVCAM-1 than controls (both p < 0.001). The difference was sustained after adjustment for TSH and levothyroxine use. Regression analysis demonstrated that sICAM-1 was related to anti-TPO (p < 0.001), and sVCAM-1 was related to both anti-TPO and-TG (p < 0.001 and p = 0.03, respectively); this relationship was sustained after adjustment for age and BMI. Although FBG and HOMA-IR were higher in the HT group, logistic regression analysis revealed that there was no effect of anti-TPO, anti-TG, sICAM-1, sVCAM 1, and C-reactive protein (CRP) on the occurrence of high FBG and high HOMA-IR. CONCLUSION: sICAM-1 and sVCAM-1 levels were significantly elevated in the patients with euthyroid HT and correlated closely with thyroid autoimmunity. However, soluble adhesion molecules had no relation with glucose metabolism parameters in the HT patients. PMID- 27366830 TI - Clinical phenotypes of obstructive airway diseases in an outpatient population. AB - BACKGROUND AND OBJECTIVES: Historically, obstructive airway diseases such as asthma and COPD are classified as different diseases. Although the definitions are clearly described, classification of patients into these traditional, clinical disease entity can be difficult. Recent evidence that there are complex, overlapping phenotypes of obstructive lung disease. Our aim was to capture clinical phenotypes of obstructive diseases through the use of cluster analysis in a representative patient population at a common Dutch pulmonary outpatient clinic. Clinical physiological and cellular/ molecular markers were used in the analysis. METHODS: To carry out the cluster analysis, an imputed dataset was created from a random sample of 191 adult patients chosen from a pulmonary outpatient clinic. The selection criteria from the sample included patients with a doctor's diagnosis for asthma or COPD. Detailed assessment of patient pulmonary function, blood eosinophil counts, allergic sensitisation and smoking history was collected. RESULTS: We observed four distinct clusters with different clinical characteristics of obstructive lung diseases. Cluster 1: patients with a history of extensive cigarette smoking, airway obstruction without signs of emphysema; cluster 2: patients with features of the emphysematous type of COPD; cluster 3: patients with characteristics of allergic asthma; cluster 4: patients with features suggesting an overlap syndrome of atopic asthma and COPD. CONCLUSION: Four phenotypes of obstructive lung disease were identified amongst patients clinically labelled as asthma or COPD. These findings emphasize the concept that there are different phenotypes of obstructive lung diseases, including overlapping and complementary disease entities. These phenotypes of chronic airways disease can serve to tailor disease management. PMID- 27366831 TI - Amygdala response to explicit sad face stimuli at baseline predicts antidepressant treatment response to scopolamine in major depressive disorder. AB - The muscarinic antagonist scopolamine produces rapid antidepressant effects in individuals with major depressive disorder (MDD). In healthy subjects, manipulation of acetyl-cholinergic transmission modulates attention in a stimulus dependent manner. This study tested the hypothesis that baseline amygdalar activity in response to emotional stimuli correlates with antidepressant treatment response to scopolamine and could thus potentially predict treatment outcome. MDD patients and healthy controls performed an attention shifting task involving emotional faces while undergoing functional magnetic resonance imaging (fMRI). We found that blood oxygenation level dependent (BOLD) signal in the amygdala acquired while MDD patients processed sad face stimuli correlated positively with antidepressant response to scopolamine. Amygdalar response to sad faces in MDD patients who did not respond to scopolamine did not differ from that of healthy controls. This suggests that the pre-treatment task elicited amygdalar activity that may constitute a biomarker of antidepressant treatment response to scopolamine. Furthermore, in MDD patients who responded to scopolamine, we observed a post-scopolamine stimulus processing shift towards a pattern demonstrated by healthy controls, indicating a change in stimulus-dependent neural response potentially driven by attenuated cholinergic activity in the amygdala. PMID- 27366832 TI - Five Years' Experience with Tenon-Conjunctival Flaps in Phthisical Eyes. AB - BACKGROUND: To evaluate the efficacy of total Tenon-conjunctival flaps (TCFs) for coverage of phthisical eyes with normal corneal sensitivity. METHODS: A retrospective chart review was performed on 142 patients with mild monocular phthisis who underwent the TCF procedure to allow monocular scleral shell fitting at the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. All patients had normal corneal sensation in their painless phthisical eye and were intolerant to cosmetic scleral shell fitting preoperatively. Consecutive patients over a five-year period were enrolled. Data were collected on functional success, duration of follow-up, and complications. The Tenon's and conjunctival layers were closed separately in 103 eyes and as a single layer in the remaining 39 eyes. Main outcome measures were functional success, defined as tolerance to the prosthetic scleral shell, and rate of postoperative complications such as wound retraction, epithelial cysts, and blepharoptosis. Fisher's exact test was used to analyze the association between the main outcome measures and type of flap closure. RESULTS: The mean duration of follow-up was 23.7+/-17.43 months. Functional success was achieved in 98.6% of eyes. Minor complications included epithelial inclusion cysts in 10 (7.04%) eyes and mild blepharoptosis in 9 (6.34%) eyes. Overall flap retraction was noted in 14 (9.86%) eyes. This complication occurred in 13 of 103 (33.3%) eyes with double layer closure and in 1 of 39 (0.97%) eyes with a single layer flap closure (p=0.11). CONCLUSIONS: TCF is an effective procedure to increase corneal thickness for coverage in phthisical eyes with positive corneal sensation. The incorporation of Tenon's capsule in the flap did not increase complications with a frequency similar to the classic Gundersen procedure. PMID- 27366833 TI - Policy Framework for Covering Preventive Services Without Cost Sharing: Saving Lives and Saving Money? AB - The US Affordable Care Act mandates that private insurers cover a list of preventive services without cost sharing. The list is determined by 4 expert committees that evaluate the overall health effect of preventive services. We analyzed the process by which the expert committees develop their recommendations. Each committee uses different criteria to evaluate preventive services and none of the committees consider cost systematically. We propose that the existing committees adopt consistent evidence review methodologies and expand the scope of preventive services reviewed and that a separate advisory committee be established to integrate economic considerations into the final selection of free preventive services. The comprehensive framework and associated criteria are intended to help policy makers in the future develop a more evidence-based, consistent, and ethically sound approach. PMID- 27366834 TI - Reason, Emotion, and Implanted Devices. PMID- 27366835 TI - The Curious Case of the De-ICD: Negotiating the Dynamics of Autonomy and Paternalism in Complex Clinical Relationships. AB - This article discusses the response of our ethics consultation service to an exceptional request by a patient to have his implantable cardioverter defibrillator (ICD) removed. Despite assurances that the device had saved his life on at least two occasions, and cautions that without it he would almost certainly suffer a potentially lethal cardiac event within 2 years, the patient would not be swayed. Although the patient was judged to be competent, our protracted consultation process lasted more than 8 months as we consulted, argued with, and otherwise cajoled him to change his mind, all to no avail. Justifying our at times aggressive paternalistic intervention helped us to reflect on the nature of autonomy and the dynamics of the legal, moral, and personal relationships in the clinical decision-making process. PMID- 27366836 TI - Overriding Patient Autonomy to Enhance It: Not the Role of a Consultation Team. PMID- 27366837 TI - Lack of Agreement With What We Think Is Right Does Not Necessarily Equal an Ethical Problem: Respecting Patients' Goals of Care. PMID- 27366838 TI - The Structure of Autonomy-Paternalism: An Exercise in Framing and Reframing. PMID- 27366839 TI - Can You Restore My "Own" Body? A Phenomenological Analysis of Relational Autonomy. PMID- 27366840 TI - Social Paternalism in a Communitarian Context: Enhancing Individuals' Moral Deliberation Through a Communal "Moral Voice". PMID- 27366841 TI - Not Half So Curious: Legal Competence Is Not Informed Consent. PMID- 27366842 TI - Implantable Devices Should Come With a Contract. PMID- 27366843 TI - Analysis From a Fourth Perspective: Professionalism. PMID- 27366844 TI - Omnipotence and Impotence: The Need for Conversation When Patients and Clinicians Disagree. PMID- 27366845 TI - IRB and Research Regulatory Delays Within the Military Health System: Do They Really Matter? And If So, Why and for Whom? AB - Institutional review board (IRB) delays may hinder the successful completion of federally funded research in the U.S. military. When this happens, time sensitive, mission-relevant questions go unanswered. Research participants face unnecessary burdens and risks if delays squeeze recruitment timelines, resulting in inadequate sample sizes for definitive analyses. More broadly, military members are exposed to untested or undertested interventions, implemented by well intentioned leaders who bypass the research process altogether. To illustrate, we offer two case examples. We posit that IRB delays often appear in the service of managing institutional risk, rather than protecting research participants. Regulators may see more risk associated with moving quickly than risk related to delay, choosing to err on the side of bureaucracy. The authors of this article, all of whom are military-funded researchers, government stakeholders, and/or human subject protection experts, offer feasible recommendations to improve the IRB system and, ultimately, research within military, veteran, and civilian populations. PMID- 27366846 TI - Military Medicine Regulatory "Delays" ... Not as Bad as Advertised. PMID- 27366847 TI - We Can't Skip the Science. PMID- 27366848 TI - Improving Military IRB Efficiency: Envisioning Broader Changes. PMID- 27366849 TI - Optimizing Military Human Subjects Protection and Research Productivity: The Role of Institutional Memory. PMID- 27366850 TI - Using the IRB Harmonization and Reliance Document Can Reduce Review and Regulatory Delays for the Benefit of All. PMID- 27366852 TI - Reflections From Fellow Feds: Addressing Delays in Oversight of Federally Funded Research. PMID- 27366851 TI - Reviewing Human Subjects Research: Efficiency and Quality for the Military and Beyond. PMID- 27366853 TI - Present Challenges in Decreasing the Time for IRB Research Reviews in the Military. PMID- 27366855 TI - Response to Open Peer Commentaries on "Moral Hazard in Pediatrics". PMID- 27366857 TI - Corrigendum. PMID- 27366856 TI - Chromatin architecture underpinning transcription elongation. AB - RNA polymerase 2 (pol2) associates with enhancers and promoters, followed by transcription initiation and subsequent pausing. Upon release, pol2 proceeds into productive elongation. A wide spread view of transcription holds that during elongation, pol2 and associated factors clear the promoter proximal region to track along the chromatin fiber until a termination site is encountered. However, several studies are compatible with alternative models. One common feature among these models is that transcription elongation results from movement of the gene along a complex consisting of pol2 and associated factors. Such a scenario predicts that active enhancers and promoters that are bound by transcription complexes, including pol2 are in dynamic physical proximity with the gene body in a manner paralleling pol2 processivity. This has indeed been observed by chromosome conformation capture under conditions of synchronous transcription. Here we discuss these observations and their implication for architectural models of transcription elongation. PMID- 27366858 TI - Molecular dynamics simulations of the intrinsically disordered protein amelogenin. AB - Amelogenin refers to a class of intrinsically disordered proteins that are the major constituents of enamel matrix derivative (EMD), an extract of porcine fetal teeth used in regenerative periodontal therapy. Modifications in molecular conformation induced by external stresses, such as changes in temperature or pH, are known to reduce the effectiveness of EMD. However, detailed descriptions of the conformational behavior of native amelogenin are lacking in the open literature. In the present work, a molecular model for the secondary and tertiary structure of the full-length major porcine amelogenin P173 was constructed from its primary sequence by replica exchange molecular dynamics (REMD) simulations. The REMD results for isolated amelogenin molecules at different temperatures were shown to be consistent with the available spectroscopic data. They therefore represent an important first step toward the simulation of the intra- and intermolecular interactions that mediate self-organization in amelogenin and its behavior in the presence of other EMD components under conditions representative of its therapeutic application. PMID- 27366859 TI - Variation in Ophthalmologist Use of Antivascular Endothelial Growth Factor Therapy Among Medicare Beneficiaries. PMID- 27366860 TI - Management and reconstruction of blast wounds of the head and neck. AB - PURPOSE OF REVIEW: The purpose of this review is to highlight recent literature related to the initial management and reconstruction of blast injuries to the head and neck. RECENT FINDINGS: An increasing percentage of combat-related injuries are caused by blast trauma. Management of blast trauma over the last 10 years has improved understanding of the unique nature of these injuries and the importance of thoughtful management and reconstruction. Blast trauma is associated with an increased need for definitive airway management. As a result, initial triage principles of airway management and hemorrhage control are extremely important in the acute setting. Blast trauma results in high-velocity injuries that can lead to extensive soft tissue damage, which has important implications for reconstruction. Staging reconstruction is an important consideration for more extensive injuries. SUMMARY: Experience on the battlefield with blast injuries over the last decade has led to efficient triage with focus on hemorrhage and airway control. The lessons learned in Iraq and Afghanistan with the unique physiology of blast trauma have improved the casualty care of service members and can be used both in future military conflicts and in civilian trauma care. PMID- 27366861 TI - Absorbed dose-to-water protocol applied to synchrotron-generated x-rays at very high dose rates. AB - Microbeam radiation therapy (MRT) is a new radiation treatment modality in the pre-clinical stage of development at the ID17 Biomedical Beamline of the European synchrotron radiation facility (ESRF) in Grenoble, France. MRT exploits the dose volume effect that is made possible through the spatial fractionation of the high dose rate synchrotron-generated x-ray beam into an array of microbeams. As an important step towards the development of a dosimetry protocol for MRT, we have applied the International Atomic Energy Agency's TRS 398 absorbed dose-to-water protocol to the synchrotron x-ray beam in the case of the broad beam irradiation geometry (i.e. prior to spatial fractionation into microbeams). The very high dose rates observed here mean the ion recombination correction factor, k s , is the most challenging to quantify of all the necessary corrections to apply for ionization chamber based absolute dosimetry. In the course of this study, we have developed a new method, the so called 'current ramping' method, to determine k s for the specific irradiation and filtering conditions typically utilized throughout the development of MRT. Using the new approach we deduced an ion recombination correction factor of 1.047 for the maximum ESRF storage ring current (200 mA) under typical beam spectral filtering conditions in MRT. MRT trials are currently underway with veterinary patients at the ESRF that require additional filtering, and we have estimated a correction factor of 1.025 for these filtration conditions for the same ESRF storage ring current. The protocol described herein provides reference dosimetry data for the associated Treatment Planning System utilized in the current veterinary trials and anticipated future human clinical trials. PMID- 27366863 TI - Gender, Sexuality, and Relationships in Young Hispanic People. AB - This study explores the relation between gender differences and sexuality among young Hispanic people. Eight hundred and forty young people from Spain and Mexico filled out a self-administered questionnaire about sexuality (sexual experience, sexual orientation, and sexual relationships) and gender (self-identification). Men in both Spain and Mexico more commonly report the practice of masturbation and vaginal sex, and are more likely to be unfaithful than women. Women in both countries report more steady partners and longer length of relationships. There were greater gender differences for Mexican men and women than for Spanish men and women in terms of sexual frequency, sexual orientation, and infidelity. Therefore, gender may play an important role in young people's sexuality, more so in Mexico than in Spain. PMID- 27366864 TI - Augmenting College Students' Study of Speech-Language Pathology Using Computer Based Mini Quiz Games. AB - PURPOSE: This study examined whether undergraduate college students' immediate recall and longer-term retention of introductory voice disorder concepts improved by using mini quiz games (MQGs; interactive knowledge tests in game format) compared with (a) traditional study alone, (b) MQGs and traditional study together, or (c) a no-study control condition. METHOD: Ninety-three college students participated in proctored sessions in which they were given a pretest, viewed an online lecture on introductory voice disorder concepts, and then engaged in either no intervention or interventions including traditional study, MQG play, or both MQG play and traditional study, followed by an immediate recall posttest and longer-term retention follow-up test. RESULTS: Analyses suggested that the effects of all interventions (traditional study, MQG play, and the combination of the 2) were equivalent and resulted in significantly greater improvements from pretest to immediate recall posttest performance than the control condition. In contrast, MQGs and MQGs with traditional study, but not traditional study alone, showed better results for long-term retention than no study. CONCLUSION: Results provide preliminary support for the idea that there may be multiple effective learning modes, beyond traditional study, that enhance recall and retention of knowledge foundational to speech-language pathology clinical training and practice. PMID- 27366865 TI - Antitumor activity of combined endostatin and thymidine kinase gene therapy in C6 glioma models. AB - The combination of Endostatin (ES) and Herpes Simplex Virus thymidine kinase (HSV TK) gene therapy is known to have antitumor activity in bladder cancer. The potential effect of ES and TK therapy in glioma has not yet been investigated. In this study, pTK-internal ribosome entry site (IRES), pIRES-ES, and pTK-IRES-ES plasmids were constructed; pIRES empty vector served as the negative control. The recombinant constructs were transfected into human umbilical vein endothelial cells (HUVECs) ECV304 and C6 rat glioma cell line. Ganciclovir (GCV) was used to induce cell death in transfected C6 cells. We found that ECV304 cells expressing either ES or TK-ES showed reduced proliferation, decreased migration capacity, and increased apoptosis, as compared to untransfected cells or controls. pTK-IRES ES/GCV or pTK-IRES/GCV significantly suppressed cell proliferation and induced cell apoptosis in C6 cells, as compared to the control. In addition, the administration of pIRES-ES, pTK-IRES/GCV, or pTK-IRES-ES/GCV therapy improved animal activity and behavior; was associated with prolonged animal survival, and a lower microvessel density (MVD) value in tumor tissues of C6 glioma rats. In comparison to others, dual gene therapy in form of pTK-IRES-ES/GCV had a significant antitumor activity against C6 glioma. These findings indicate combined TK and ES gene therapy was associated with a superior antitumor efficacy as compared to single gene therapy in C6 glioma. PMID- 27366866 TI - Why the dipolar response in dielectrics and spin-glasses is unavoidably universal. AB - Materials response to electric or magnetic fields is often dominated by the dynamics of dipoles in the system. This is for instance the case of polar dielectrics and many transition metal compounds. An essential and not yet well understood fact is that, despite their structural diversity, dielectric solids exhibit a striking universality of frequency and time responses, sharing many aspects with the behaviour of spin-glasses. In this article I propose a stochastic approach to dipole dynamics within which the "universal frequency response" derives naturally with Debye's relaxation mechanism as a special case. This formulation reveals constraints to the form of the relaxation functions, which are essential for a consistent representation of the dynamical slowing-down at the spin-glass transition. Relaxation functions with algebraic-, and exponential-tails, as well as damped oscillations, are shown to have a unified representation in which the stable limit of the distribution of waiting-times between dipole flips determines the present type of dynamics. PMID- 27366868 TI - Two dimensional, electronic particle tracking in liquids with a graphene-based magnetic sensor array. AB - The investigation and control of liquid flow at the nanometer scale is a key area of applied research with high relevance to physics, chemistry, and biology. We introduce a method and a device that allows the spatial resolution of liquid flow by integrating an array of graphene-based magnetic (Hall) sensors that is used for tracking the movement of magnetic nanoparticles immersed in a liquid under investigation. With a novel device concept based on standard integration processes and experimentally verified material parameters, we numerically simulate the performance of a single sensor pixel, as well as the whole sensor array, for tracking magnetic nanoparticles having typical properties. The results demonstrate that the device enables (a) the detection of individual nanoparticles in the liquid with high accuracy and (b) the reconstruction of a particle's flow driven trajectory across the integrated sensor array with sub-pixel precision as a function of time, in what we call the "Magnetic nanoparticle velocimetry" technique. Since the method does not rely on optical detection, potential lab-on chip applications include particle tracking and flow analysis in opaque media at the sub-micron scale. PMID- 27366867 TI - Infliximab ameliorating depression-like behavior through inhibiting the activation of the IDO-HAAO pathway mediated by tumor necrosis factor-alpha in a rat model. AB - In recent years, some studies have suggested that the activation of inflammatory system plays a role in the occurrence of depression. Tumor necrosis factor-alpha (TNF-alpha), as one of the preinflammatory cytokines, has been reported to be involved in the occurrence of various diseases including depression. Infliximab, an antagonist of TNF-alpha, is usually used to treat some autoimmune diseases such as Crohn's disease and can perhaps be used to treat other diseases. In this study, the antidepressant effect and a possible mechanism of infliximab were investigated by studying the depression-like behavior and expression of TNF alpha, indoleamine 2, 3-dioxygenase (IDO), and 3-hydroxyl amino acid oxygenase (HAAO) from the cortex and hippocampus in rat exposed to chronic unpredicted stress. Forty male Sprague-Dawley rats were divided into a control group (CG), an infliximab-treated control group, a model group (MG), and an infliximab-treated model group (IFXM). Infliximab (5 mg/kg once week) was administered to the infliximab-treated control group and IFXM rats by an intraperitoneal injection, whereas an equivalent volume of vehicle was administered to CG and MG rats. Rat behaviors and the expression of TNF-alpha, IDO, and HAAO in the cortex and hippocampus were determined. It was found that a significant relief in depression like behaviors was observed with a downregulation of TNF-alpha, IDO, and HAAO expression in the IFXM rats compared with MG rats. The results show the antidepressant effect of infliximab and suggest that its mechanism is partly related to inhibition of IDO-HAAO pathway activation mediated by TNF-alpha in rat brain. PMID- 27366869 TI - The Role of SPECT/CT Lymphoscintigraphy and Radioguided Sentinel Lymph Node Biopsy in Managing Papillary Thyroid Cancer. AB - IMPORTANCE: Single-photon emission computed tomography/computed tomography (SPECT/CT) and radioguided sentinel lymph node biopsy (rSLNB) are techniques that could potentially benefit surgeons and pathologists in the identification of sentinel lymph node (SLN) metastases in patients with papillary thyroid carcinoma (PTC). Evidence suggests that these novel techniques lead to substantial changes in PTC management by reducing understaging and of occult lymph node (LN) metastases and optimizing neck surgery by increasing the necessity of lateral lymphadenectomy and decreasing central lymphadenectomy. OBJECTIVES: To correlate the presence of LN metastases in PTC with clinical and pathological features using SPECT/CT and rSLNB. DESIGN, SETTING, AND PARTICIPANTS: For this prospective cohort study from June 2010 to November 2013, 42 patients with thyroid nodules suspicious for papillary carcinoma or classified as malignant on cytology examination without suspicion of lymph node metastases by clinical and ultrasound examinations were recruited from a single public medical institution. INTERVENTIONS: All 42 patients underwent preoperative lymphoscintigraphy after an ultrasound-guided peritumoral injection of Technetium Tc 99m nanocolloid. Cervical images were acquired with a SPECT/CT scanner 15 minutes after radiotracer injection. Approximately 2 hours after lymphoscintigraphy, the patients were submitted to intraoperative rSLNB using a handheld gamma probe. All SLNs identified were removed alongside with non-SLNs from the same compartment. Papillary thyroid carcinoma, SLNs and non-SLNs were submitted for histopathology and immunohistochemical analyses. RESULTS: Of the 42 patients initially enrolled, 37 were included in analysis, including 6 men and 31 women with a mean (range) age of 47 (22-83) years. Overall, T stage was as follows: T1, 23 patients (62.2%); T2, 8 patients (21.6%); and T3, 6 patients (16.2%). Sentinel lymph nodes were identified in 92% of the patients, and among these metastases were present in 17 patients (46%). The SLNs were false-negative in 3 patients. Metastases in the lateral compartment ocurred in 7 patients (18%). There was a significant association between LN metastases and tumor size (odds ratio, 1.06; 95% CI, 1.00 1.13; P = .02), with a Cohen d effect of 0.683 (medium to large effect). Overall, 17 patients (46%) with LN metastases had management changed because they were submitted to higher radioiodine ablation doses and closer clinical surveillance. CONCLUSIONS AND RELEVANCE: Radioguided SLNB is able to detect occult cervical lymph node metastases in patients with papillary thyroid carcinoma, and in 7 patients (18%) rSLNB detected lymph node metastases in the lateral compartments. The rSLNB technique lead to management change in 14 patients (37.8%). PMID- 27366870 TI - Detectability of designer benzodiazepines in CEDIA, EMIT II Plus, HEIA, and KIMS II immunochemical screening assays. AB - The emerging new psychoactive substances made available for recreational drug use have recently started to include designer benzodiazepines. As a consequence, the routine immunoassay drug testing for benzodiazepines may become less effective, due to an increased occurrence of 'false negative' and 'false positive' results. This work aimed to extend the knowledge of analytical cross-reactivity of 13 designer benzodiazepines in the CEDIA, EMIT II Plus, HEIA, and KIMS II immunoassays. Urine standards were prepared by spiking blank urine with clonazolam, deschloroetizolam, diclazepam, estazolam, etizolam, flubromazepam, flubromazolam, flutazolam, 3-hydroxyphenazepam, meclonazepam, nifoxipam, phenazepam, and pyrazolam. Authentic urine samples from intoxication cases identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were also investigated. For the spiked standard samples, the 13 designer benzodiazepines generally showed a high cross-reactivity in all assays. This was further confirmed when investigating their detectability in authentic urine samples from cases of drug intake. The test responses also indicated additional reactivity from metabolites. The lowest detectability in spiked samples was observed for flutazolam, which shows the most divergent chemical structure compared with the other benzodiazepines. Overall, the KIMS II and CEDIA immunoassays, which both include enzymatic hydrolysis of conjugated forms, showed the highest, and EMIT II Plus the lowest degree of reactivity, for spiked parent substances and authentic urine specimens. The results of this study demonstrated that designer benzodiazepines can be detected in standard urine immunoassay drug screening and this should be taken into consideration when performing confirmation analysis. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27366872 TI - Erratum. PMID- 27366871 TI - Hypoxia suppresses myocardial survival pathway through HIF-1alpha-IGFBP-3 dependent signaling and enhances cardiomyocyte autophagic and apoptotic effects mainly via FoxO3a-induced BNIP3 expression. AB - The HIF-1alpha transcriptional factor and the BH-3 only protein BNIP3 are known to play fundamental roles in response to hypoxia. The objective of this research is to investigate the molecular mechanisms and the correlation of HIF-1alpha, BNIP3 and IGFBP-3 in hypoxia-induced cardiomyocytes injuries. Heart-derived H9c2 cells and neonatal rat ventricular myocytes (NRVMs) were incubated in normoxic or hypoxic conditions. Hypoxia increased HIF-1alpha expression and activated the downstream BNIP3 and IGFBP-3 thereby triggered mitochondria-dependent apoptosis. Moreover, IGF1R/PI3K/Akt signaling was attenuated by HIF-1alpha-dependent IGFBP-3 expression to enhance hypoxia-induced apoptosis. Autophagy suppression with 3 methyladenine or siATG5 or siBeclin-1 significantly decreased myocardial apoptosis under hypoxia. Knockdown of FoxO3a or BNIP3 significantly abrogated hypoxia-induced autophagy and mitochondria-dependent apoptosis. Moreover, prolonged-hypoxia induced HIF-1alpha stimulated BNIP3 and enhanced IGFBP-3 activation to inhibit IGF1R/PI3K/Akt survival pathway and mediate mitochondria dependent cardiomyocyte apoptosis. HIF-1alpha and FoxO3a blockage are sufficient to annul the change of excessive hypoxia of hearts. PMID- 27366873 TI - Prevention of Congenital Disorders and Care of Affected Children: A Consensus Statement. AB - As the Sustainable Development Goals are adopted by United Nations member states, children with congenital disorders remain left behind in policies, programs, research, and funding. Although this finding was recognized by the creation and endorsement of the 63rd World Health Assembly Resolution in 2010 calling on United Nations member states to strengthen prevention of congenital disorders and the improvement of care of those affected, there has been little to no action since then. The Sustainable Development Goals call for the global health and development community to focus first and foremost on the most vulnerable and those left behind in the Millennium Development Goal era. To maximize the opportunity for every woman and couple to have a healthy child and to reduce the mortality and severe disability associated with potentially avoidable congenital disorders and their consequences for the children affected, their families and communities, and national health care systems, we propose priority measures that should be taken urgently to address this issue. PMID- 27366875 TI - Is there really a relationship between mean platelet volume and euthyroid Hashimoto's thyroiditis? PMID- 27366874 TI - Abciximab as a bridging strategy to overcome morphine-prasugrel interaction in STEMI patients. AB - OBJECTIVE: The present study investigated whether the glycoprotein (GP)IIb/IIIa receptor blocker abciximab might be a successful bridging strategy to achieve adequate levels of platelet inhibition rapidly in cases where prasugrel is used in morphine-pretreated ST-elevation myocardial infarction (STEMI) patients. METHODS: In a prospective observational cohort study, 32 patients presenting with STEMI were given prasugrel at a loading dose of 60 mg. Patients were stratified into four groups, according to morphine and/or abciximab use. Adenosine diphosphate (ADP)-induced platelet aggregation was measured at four time points: at baseline, and at 2 h, 1 day and 2 days after prasugrel loading. RESULTS: Morphine use was associated with a three-fold higher level of ADP-induced platelet aggregation 2 h after prasugrel loading compared with no morphine/no abciximab (P = 0.019). However, when abciximab was infused in the catheterization laboratory, the effect of morphine on ADP-induced platelet aggregation disappeared (P = 0.884). This interaction was also seen in the presence of high on-treatment platelet reactivity (HTPR) at 2 h; while HTPR was seen in 88% of morphine users/no abciximab users, it was found in only 17-20% in the three other groups (P = 0.003). The effect of morphine disappeared by day 1 - 2. CONCLUSION: The infusion of the GPIIb/IIIa receptor blocker abciximab allows immediate and efficient platelet inhibition in STEMI patients concomitantly receiving the oral ADP receptor blocker prasugrel and morphine. PMID- 27366876 TI - Binge-Eating Disorder Comes of Age. PMID- 27366877 TI - Role of Bladder Dysfunction in Men with Lower Urinary Tract Symptoms Refractory to Alpha-blocker Therapy: A Video-urodynamic Analysis. AB - OBJECTIVES: Lower urinary tract symptoms (LUTS) in men result from a complex interplay of pathophysiology, including bladder and bladder outlet dysfunction. This study retrospectively analyzed bladder dysfunction in men with LUTS based on the results of video-urodynamic studies (VUDS). METHODS: Male patients (aged >=40 years), with LUTS and an International Prostate Symptom Score of 8 or more, who were refractory to alpha-blocker treatment were retrospectively recruited and evaluated with VUDS and total prostate volume (TPV). Patients were further divided into subgroups of bladder dysfunction and bladder outlet dysfunction according to characteristic VUDS findings. Age, TPV and VUDS findings were compared among different subgroups. RESULTS: After VUDS, bladder outlet obstruction (BOO) was only noted in 48.6% of men. Of patients, 919 of 2991 (30.7%) had bladder dysfunction including detrusor underactivity (DU, 5.1%), detrusor overactivity and inadequate contractility (DHIC, 5.3%), detrusor overactivity (DO, 17%) and hypersensitive bladder (HSB, 3.3%). In addition, 1941 (64.9%) had bladder outlet dysfunction including BOO + DO (33.8%), BOO alone (14.8%), and poor urethral sphincter relaxation (PRES, 16.3%). Among the 1519 patients with DO, 66.6% (1012) had BOO while, among 1454 patients with BOO, 69.5% (1010) had DO. Patients with DHIC, DU and DO were 5 years older than patients with HSB and normal men. TPV was significantly smaller in patients with DHIC, DU and DO as compared with BOO + DO. CONCLUSION: Approximately one-third of male LUTS was due to bladder dysfunction. A man older than 70 years with LUTS and TPV less than 30 mL usually indicates the presence of bladder dysfunction rather than BOO. PMID- 27366878 TI - Development of a high sensitivity C-reactive protein immunoassay and comparison with a commercial kit. AB - C-reactive protein (CRP) is intricately sensitive marker of inflammation, infection, and tissue damage. Role in the prognosis of heart diseases has been recently discovered. This study aimed to develop a cost-effective and high sensitivity CRP immunoassay for use in cardiac risk assessment. Assay was optimized for coating, blocking of capturing antibody, dilution, and reaction time of the conjugate and sample volume. For normal reference range, CRP was determined in serum samples from apparently healthy volunteers. For clinical validation, CRP was determined in samples of acute coronary syndrome patients by in-house and commercial assays. The lower detection limit of in-house assay was 0.16 ug/L. Intra and inter assay imprecision was 4.39%, 4.6% and 8.6%, 9.3%, respectively. The correlation between the CRP levels by the two assays was r = 0.861. Sensitivity, specificity, predictive value for a positive test, and a negative test of in-house assay was 95.3%, 92.8%, 95.3%, and 92.8%, respectively. At lower-end CRP levels of both kits correlated very well but showed variation at upper end. In-house assay showed high sensitivity and reliability at lower end and it is hoped that will help to evaluate cardiac risk assessment (after improvement at upper end) in clinically poor settings. PMID- 27366879 TI - Toxicity of squamocin on Aedes aegypti larvae, its predators and human cells. AB - BACKGROUND: The mosquito Aedes aegypti transmits a virus that causes diverse human diseases, and control of the vector is an important strategy to avoid disease propagation. Plants in the family Annonaceae are recognised as sources of molecules with uses in the medical and agriculture fields. Molecules of secondary metabolites of Annonaceae plants exhibit insecticidal potential against insect pests and vectors, especially acetogenins, showing high toxicity at low doses, which has encouraged research into producing new insecticide molecules. Herein, we identify an acetogenin from Annona mucosa seeds (chemical analysis) and provide the results of toxicity tests against larvae of A. aegypti (target insect) and its predators Culex bigoti and Toxorhynchites theobaldi (non-target insects) and cytotoxicity to human leukocytes. RESULTS: We identified squamocin (C37 H66 O7 ), a fatty acid with a bis-tetrahydrofuran ring. In A. aegypti, this compound caused behavioural disturbance before larval death and high mortality at low concentrations (LC50 = 0.01 ug mL-1 and LC90 = 0.11 ug mL-1 ). However, in predators and human leukocytes, squamocin showed no toxicity effect, indicating the selectivity of this molecule for non-target organisms. CONCLUSION: We identified squamocin from A. mucosa seeds, which exhibited lethal action against A. aegypti and showed selectivity for non-target insects and low cytotoxicity to human cells. (c) 2016 Society of Chemical Industry. PMID- 27366880 TI - Conventional carotid endarterectomy versus stenting: comparison of restenosis rates in arteries with identical predisposing factors. AB - BACKGROUND: The aim of the study was to investigate the possible role of individual predisposition in the pathogenesis of carotid restenosis. METHODS: Over 1700 patients have undergone carotid endarterectomy (CEA) in our institute over the past 15 years. We retrospectively reviewed the charts of those who also had contralateral carotid stenting (CAS) for primary atherosclerotic stenosis and recorded the rates of post-CEA and post-CAS restenosis >=50%. RESULTS: In the 29 cases analyzed (21 men/8 women), CEA was performed with conventional technique and direct suturing in most cases. Mean ages at the time of CEA and CAS were 69.2+/-6.6 and 73+/-6.7 yrs, respectively, and risk profiles at the 2 time points were similar: hypertension (96.5%), dyslipidemia (55.2%), smoking (51.7%), diabetes (31%), coronary artery disease (48.3%), chronic obstructive pulmonary disease (37.9%), and chronic renal failure (13.8%). Antiplatelet therapy protocols were identical for the two procedures. During follow-up (mean: 67.25+/ 51.6 months after CEA, 24.6+/-16.9 months after CAS), Duplex scans revealed restenosis in 12 patients (9 arteries treated with CEA, 6 managed with CAS). In three patients, restenosis was bilateral. Restenosis-free survival rates at five years were 85% after CEA and 66% after CAS (P=NS). CONCLUSIONS: In this selected group of patients, CEA and CAS were associated with a similar incidence of restenosis. Only 25% of the patients who developed restenosis did so after both procedures. These preliminary findings indicate that individual predisposition does not play a crucial role in the pathogenesis of restenosis. To confirm this conclusion, an analysis of a much larger, multicenter cohort is essential. PMID- 27366881 TI - Thrombin injection and compression with removable guidewire in the treatment of postcatheterization femoral pseudoaneurysm. AB - BACKGROUND: The purpose of our study was to determine the efficacy of percutaneous thrombin treatment for iatrogenic femoral artery pseudoaneurysms (FAP) and to identify those criteria that may help to predict increased treatment failure risk and complications. METHODS: A number of 32 iatrogenic femoral pseudoaneurysms were treated with US-guided thrombin injection (group A), while four elderly patient with complex femoral pseudoaneurysm underwent compression assisted by removable "guidewire" (group B). Twenty-five were classified as simple (single lobe) and 11 as complex (at least two lobes with a single neck to the native vessel). Pseudoaneurysm volume, classification, thrombin dose, anticoagulation therapy status, and sheath size were considered independent prognostic factors. RESULTS: All the 36 patients (pts) had initial complete femoral pseudoaneurysms thrombosis. The aneurysm was thrombosed on a Doppler ultrasound (US) follow-up in all the cases but four (group A), those who required the additional thrombin injection. A fatal complication occurred in one patient with complex FAP (group A). CONCLUSIONS: Preliminary data suggest that US-guided percutaneous thrombin injection is a safe and effective method to treat iatrogenic pseudoaneurysms. Simple iatrogenic femoral pseudoaneurysms benefit a single injection of up to 500 units of topical thrombin. We recommend more caution in complex pseudoaneurysms treatment; it is preferable to perform thrombin injection first into the lobe which is not directly joined to the femoral artery. A longer bed rest and closer observation are mandatory during the subsequent 24 hours. If the lobe communicating with the femoral artery is still patent, it can be retreated. Alternatively, we propose a new strategy approach through compression assisted removable "guidewire". PMID- 27366882 TI - Recent developments in the management of adult coarctation. PMID- 27366883 TI - Concomitant aortic arch reconstruction using deep hypothermic circulatory arrest during heart transplantation. PMID- 27366884 TI - Membrane properties in small cutaneous nerve fibers in humans. AB - INTRODUCTION: Assessment of membrane properties is important for understanding the mechanisms of painful peripheral neuropathy, developing new diagnostic techniques, and screening/profiling of analgesics that target ion channels. METHODS: Small cutaneous nerves were activated electrically by small diameter (0.2 mm) cathodes, and large nerves were activated by ordinary patch electrodes. This new perception threshold tracking method combines perception threshold assessment and stimulation paradigms from conventional threshold tracking. RESULTS: The strength-duration time-constant of large fibers (580 us +/- 160 us) was lower than the time constant of small fibers (1060 us +/- 690 us; P < 0.01, paired t-test). Threshold electrotonus showed similar threshold reductions to sub threshold prepulses, except for 80 ms hyperpolarizing prepulses, to which small fibers showed less threshold reduction than large fibers (repeated-measures analysis of variance, Bonferroni, P = 0.006). CONCLUSIONS: This is a reliable method to investigate the membrane properties of small cutaneous nerve fibers in humans and may be used in clinical settings as a diagnostic or profiling tool. Muscle Nerve 55: 195-201, 2017. PMID- 27366886 TI - Water based on a molecular model behaves like a hard-sphere solvent for a nonpolar solute when the reference interaction site model and related theories are employed. AB - For neutral hard-sphere solutes, we compare the reduced density profile of water around a solute g(r), solvation free energy MU, energy U, and entropy S under the isochoric condition predicted by the two theories: dielectrically consistent reference interaction site model (DRISM) and angle-dependent integral equation (ADIE) theories. A molecular model for water pertinent to each theory is adopted. The hypernetted-chain (HNC) closure is employed in the ADIE theory, and the HNC and Kovalenko-Hirata (K-H) closures are tested in the DRISM theory. We also calculate g(r), U, S, and MU of the same solute in a hard-sphere solvent whose molecular diameter and number density are set at those of water, in which case the radial-symmetric integral equation (RSIE) theory is employed. The dependences of MU, U, and S on the excluded volume and solvent-accessible surface area are analyzed using the morphometric approach (MA). The results from the ADIE theory are in by far better agreement with those from computer simulations available for g(r), U, and MU. For the DRISM theory, g(r) in the vicinity of the solute is quite high and becomes progressively higher as the solute diameter d U increases. By contrast, for the ADIE theory, it is much lower and becomes further lower as d U increases. Due to unphysically positive U and significantly larger |S|, MU from the DRISM theory becomes too high. It is interesting that MU, U, and S from the K H closure are worse than those from the HNC closure. Overall, the results from the DRISM theory with a molecular model for water are quite similar to those from the RSIE theory with the hard-sphere solvent. Based on the results of the MA analysis, we comparatively discuss the different theoretical methods for cases where they are applied to studies on the solvation of a protein. PMID- 27366885 TI - Circuitry to explain how the relative number of L and M cones shapes color experience. AB - The wavelength of light that appears unique yellow is surprisingly consistent across people even though the ratio of middle (M) to long (L) wavelength sensitive cones is strikingly variable. This observation has been explained by normalization to the mean spectral distribution of our shared environment. Our purpose was to reconcile the nearly perfect alignment of everyone's unique yellow through a normalization process with the striking variability in unique green, which varies by as much as 60 nm between individuals. The spectral location of unique green was measured in a group of volunteers whose cone ratios were estimated with a technique that combined genetics and flicker photometric electroretinograms. In contrast to unique yellow, unique green was highly dependent upon relative cone numerosity. We hypothesized that the difference in neural architecture of the blue-yellow and red-green opponent systems in the presence of a normalization process creates the surprising dependence of unique green on cone ratio. We then compared the predictions of different theories of color vision processing that incorporate L and M cone ratio and a normalization process. The results of this analysis reveal that-contrary to prevailing notions- postretinal contributions may not be required to explain the phenomena of unique hues. PMID- 27366887 TI - Anabolic steroids: Lots of muscle in the short-term, potentially devastating health consequences in the long-term. PMID- 27366888 TI - Detection of Cell Proliferation Markers by Immunofluorescence Staining and Microscopy Imaging in Paraffin-Embedded Tissue Sections. AB - This unit describes a step-by-step protocol to detect and quantify proliferating cells in paraffin-embedded tissue sections. Two well-established markers of proliferation (incorporation of BrdU into newly synthesized DNA and expression of the nuclear protein Ki67) are detected after antigen-retrieval and subsequent immunofluorescence staining and confocal microscopy. (c) 2016 by John Wiley & Sons, Inc. PMID- 27366889 TI - AAV9 Delivery of shRNA to the Mouse Heart. AB - RNA interference (RNAi) is a rapid approach to dissect loss-of-function phenotype for a gene of interest. However, it is challenging to perform RNAi in specific organs and tissues in vivo. Engineered viruses can provide a useful tool for delivery of small RNAs in vivo. Recombinant adeno-associated viruses (rAAVs) are the preferred method for delivering genes or gene modulators to target cells due to their high titer, low immune response, ability to transduce many types of cell, and overall safety. In this unit, we describe protocols for use of rAAVs as a cargo to deliver miRNA backbone-based shRNA controlled by a cardiac-specific promoter into the mouse heart. (c) 2016 by John Wiley & Sons, Inc. PMID- 27366891 TI - Practical Considerations for Using Pooled Lentiviral CRISPR Libraries. AB - CRISPR/Cas9 technology is ideally suited for genome-wide screening applications due to the ease of generating guide RNAs (gRNAs) and the versatility of Cas9 or Cas9 derivatives to knockout, repress, or activate expression of target genes. Several pooled lentiviral CRISPR libraries have been developed and are now publicly available, but while using CRISPR/Cas9 for genetic experiments has become widely adopted, genome-wide screening experiments remain technically challenging. This review covers the basics of CRISPR/Cas9, describes several publicly available CRISPR libraries, and provides a general protocol for conducting genome-wide screening experiments using CRISPR/Cas9. (c) 2016 by John Wiley & Sons, Inc. PMID- 27366890 TI - Introduction to Gene Editing and Manipulation Using CRISPR/Cas9 Technology. AB - Until very recently, the prospect of introducing mutations or exogenous DNA sequences at precise locations in the genomes of plants and animals was difficult, if not impossible. This rapidly changed with the demonstration that the type II CRISPR-Cas complex, a bacterial anti-viral surveillance system, could be engineered into a simple and robust platform for introducing double-stranded DNA breaks at nearly any position of plant and animal genomes. The prospect of efficiently creating tailored changes to a gene of interest is revolutionizing biomedical research, allowing exciting new questions to be asked. This overview introduces CRISPR-Cas technology as a tool for molecular biology and briefly discusses the advantages of this method over earlier techniques, as well as unique opportunities to create new avenues of research. (c) 2016 by John Wiley & Sons, Inc. PMID- 27366892 TI - CRISPR/Cas9-Based Multiplex Genome Editing in Monocot and Dicot Plants. AB - The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 mediated genome targeting system has been applied to a variety of organisms, including plants. Compared to other genome-targeting technologies such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), the CRISPR/Cas9 system is easier to use and has much higher editing efficiency. In addition, multiple "single guide RNAs" (sgRNAs) with different target sequences can be designed to direct the Cas9 protein to multiple genomic sites for simultaneous multiplex editing. Here, we present a procedure for highly efficient multiplex genome targeting in monocot and dicot plants using a versatile and robust CRISPR/Cas9 vector system, emphasizing the construction of binary constructs with multiple sgRNA expression cassettes in one round of cloning using Golden Gate ligation. We also describe the genotyping of targeted mutations in transgenic plants by direct Sanger sequencing followed by decoding of superimposed sequencing chromatograms containing biallelic or heterozygous mutations using the Web-based tool DSDecode. (c) 2016 by John Wiley & Sons, Inc. PMID- 27366893 TI - CRISPR-Cas9-Guided Genome Engineering in C. elegans. AB - The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) system is successfully being used for efficient and targeted genome editing in various organisms, including the nematode C. elegans. Recent studies have developed various CRISPR-Cas9 approaches to enhance genome engineering via two major DNA double-strand break repair pathways: non-homologous end joining and homologous recombination. Here we describe a protocol for Cas9 mediated C. elegans genome editing together with single guide RNA (sgRNA) and repair template cloning, as well as injection methods required for delivering Cas9, sgRNAs, and repair template DNA into the C. elegans germline. (c) 2016 by John Wiley & Sons, Inc. PMID- 27366894 TI - A Microbiome DNA Enrichment Method for Next-Generation Sequencing Sample Preparation. AB - "Microbiome" is used to describe the communities of microorganisms and their genes in a particular environment, including communities in association with a eukaryotic host or part of a host. One challenge in microbiome analysis concerns the presence of host DNA in samples. Removal of host DNA before sequencing results in greater sequence depth of the intended microbiome target population. This unit describes a novel method of microbial DNA enrichment in which methylated host DNA such as human genomic DNA is selectively bound and separated from microbial DNA before next-generation sequencing (NGS) library construction. This microbiome enrichment technique yields a higher fraction of microbial sequencing reads and improved read quality resulting in a reduced cost of downstream data generation and analysis. (c) 2016 by John Wiley & Sons, Inc. PMID- 27366895 TI - Depletion of Ribosomal RNA Sequences from Single-Cell RNA-Sequencing Library. AB - Recent advances in single-cell RNA sequencing technologies have revealed high heterogeneity of gene expression profiles in individual cells. However, most current single-cell RNA-seq methods use oligo-dT priming in the reverse transcription steps and detect only polyA-positive for more accuracy, since there are also polyA-positive non-coding RNAs transcripts, not other important RNA species, such as polyA-negative noncoding RNA. Reverse transcription using random oligos enables detection of not only the noncoding RNA species without polyA tails, but also ribosomal RNA (rRNA). rRNA comprises more than 90% of the total RNA and should be depleted from the RNA-seq library to ensure efficient usage of the sequencing capacity. Commonly used hybridization-based rRNA depletion methods can preserve noncoding RNA in the standard RNA-seq library. However, such rRNA depletion methods require high input amounts of total RNA and do not work at the single-cell level or with limited input DNA. This unit describes a novel procedure for RNA-seq library construction from single cells or a minimal amount of RNA. A thermostable duplex-specific nuclease is used in this method to effectively remove ribosomal RNA sequences following whole-transcriptome amplification and sequencing library construction. (c) 2016 by John Wiley & Sons, Inc. PMID- 27366896 TI - Dynamic Optical Coherence Tomography Capillaroscopy: A New Imaging Tool in Autoimmune Connective Tissue Disease. AB - Importance: Vasculopathy characterized by functional and structural abnormalities of the microcirculation plays an important role in systemic sclerosis and dermatomyositis. Although there are several advantages in using capillaroscopy, the method does not offer insight on the skin architecture, flow status, or morphology of the deeper dermal vessels. Dynamic optical coherence tomography (D OCT) is a recently developed OCT technique that enables detection of high-speed changes in back-scattered light caused by moving cells in vessels. The high resolution of OCT enables the detection of the papillary loops. Objective: To explore the potential for OCT capillaroscopy of the nailfolds using D-OCT. Design, Setting, and Participants: In this case series study of 4 participants, the nailfolds in 2 patients with systemic sclerosis, 1 patient with dermatomyositis, and a healthy volunteer were scanned using D-OCT. The included patients were all outpatients from the department of dermatology at Bispebjerg Hospital. Data were analyzed from November 2015 to February 2016. Main Outcomes and Measures: Dynamic OCT capillaroscopy revealed a potential for imaging of the capillary morphology, the surrounding skin architecture, and flow status of the capillaries in the nailfold. Moreover, D-OCT quantified evident changes of the blood flow in normal nailfold capillaries after application of nitroglycerine and brimonidine. Results: This case series included 4 adult women. The quantitative measurements of the blood flow in the D-OCT images of the healthy participant showed significant quantitative differences in blood flow before and after application of nitroglycerine (mean difference, 0.035; 95% CI, 0.008-0.061; P = .02) and brimonidine (mean difference, -0.015; 95% CI, -0.082 to -0.039; P < .001). In the dermatomyositis patient, the en face D-OCT images showed a striking detailed Y-shaped dilated capillary correlating with the clinical finding. In the 2 patients with systemic sclerosis, D-OCT depicted megacapillaries, as well as loss of capillaries. Moreover, cross-sectional OCT images demonstrated a characteristic loss of distinct dermo-epidermal junction and more compact dermis with loss of adnexal structures. Conclusions and Relevance: Compared with conventional capillaroscopy, D-OCT offers second-to-none information on nailfold capillary morphology, overall skin architecture, as well as quantitative data on vascular abnormalities and blood flow in the nailfold in a single scan. PMID- 27366897 TI - Perioperative and Long-term Outcomes After Carotid Endarterectomy in Hemodialysis Patients. AB - Importance: Early landmark trials excluding dialysis patients showed carotid endarterectomy (CEA) decreased stroke risk compared with medical management. Dialysis dependence has been associated with poor outcomes after CEA in small studies, but, to our knowledge, there are no large studies evaluating outcomes of CEA in this patient group. Objective: To delineate perioperative and long-term outcomes after CEA in dialysis-dependent patients in a large national database. Design, Setting, and Participants: A retrospective review of all patients who underwent CEA in the US Renal Disease System-Medicare-matched database between January 1, 2006, and December 31, 2011, was performed in June 2015. The median follow-up time was 2.5 years. Logistic and Cox regression analyses were used to evaluate perioperative and long-term outcomes. Main Outcomes and Measures: The primary outcomes of interest were perioperative stroke, myocardial infarction and mortality, and long-term stroke and mortality. Results: A total of 5142 patients were studied; 83% of whom were asymptomatic. The mean (SD) age was 68.9 (9.6) years for asymptomatic patients and 70.0 (9.1) years for symptomatic patients. The 30-day stroke rate, myocardial infarction, and mortality for the asymptomatic and symptomatic groups were 2.7% vs 5.2% (P = .001), 4.6% vs 5.0% (P = .69), and 2.6% vs 2.9% (P = .61), respectively. Predictors of perioperative stroke were symptomatic status (odds ratio [OR], 2.01; 95% CI, 1.18-3.42; P = .01), black race (OR, 2.30; 95% CI, 1.24-4.25; P = .008), and Hispanic ethnicity (OR, 2.28; 95% CI, 1.17-4.42; P = .02). Freedom from stroke and overall survival were lower in symptomatic compared with asymptomatic patients at 1, 2, 3, 4, and 5 years (in asymptomatic vs symptomatic patients, freedom from stroke rates were 92% vs 87% at 1 year, 88% vs 83% at 2 years, 84% vs 78% at 3 years, 80% vs 73% at 4 years, and 79% vs 69% at 5 years, respectively, and overall survival rates were 78% vs 73% at 1 year, 60% vs 57% at 2 years, 46% vs 42% at 3 years, 37% vs 32% at 4 years, and 33% vs 29% at 5 years; P < .05). Predictors of long-term stroke were preoperative symptoms (hazard ratio, 1.67; 95% CI, 1.24-2.24; P < .001), female sex (hazard ratio, 1.34; 95% CI, 1.03-1.73; P = .04), and inability to ambulate (hazard ratio, 1.81; 95% CI, 1.25-2.62; P = .002). Predictors of long-term mortality were increasing age (OR, 1.02; 95% CI, 1.01-1.03; P < .01), active smoking (OR, 1.22; 95% CI, 1.00-1.48; P = .045), history of congestive heart failure (OR, 1.25; 95% CI, 1.12-1.39; P < .001), and chronic obstructive pulmonary disease (OR, 1.26; 95% CI, 1.09-1.45; P = .002). Conclusions and Relevance: To our knowledge, this is the largest study to date of dialysis patients who have undergone CEA. We have shown that the risks of CEA in asymptomatic patients is high and may outweigh the benefits. The risk of CEA in symptomatic patients is also high, and it should only be offered to a small carefully selected cohort of symptomatic patients. PMID- 27366899 TI - Effect of NADPH-cytochrome P450 reductase on all-trans-retinoic acid efficacy and cytochrome P450 26A1 expression in human myeloid leukaemia HL-60 cells. AB - OBJECTIVES: All-trans-retinoic acid (ATRA), a naturally occurring metabolite of vitamin A, has been shown to have great potential as an antitumorigenic drug to treat acute leukaemia by promoting cancer cell differentiation. Cytochrome P450 oxidoreductase (POR) is the only obligate electron donor for all of the microsomal cytochrome P450 enzymes including CYP26A1 which is highly specific for ATRA metabolism and efficacy in human myeloid leukaemia cells. In this study, we aimed to investigate the effect of POR on ATRA efficacy and CYP26A1 expression in human myeloid leukaemia HL-60 cells. METHODS: Stably expressed POR and POR-RNAi HL-60 cell lines were established by transfecting POR overexpression or RNAi (RNA interference) vectors mediated by lentivirus. The protein expression of POR and CYP26A1 was examined by Western blot. The potential roles of POR on ATRA efficacy in HL-60 cells were explored by cell viability assay, cell cycle distribution, cellular differentiation and apoptosis analysis. KEY FINDINGS: All-trans-retinoic acid treatment caused the expression of POR upregulation and CYP26A1 downregulation in dose- and time-dependent manners. POR overexpression decreased CYP26A1 expression in HL-60 cells. When POR gene was interfered, the downregulation of CYP26A1 expression by ATRA was abolished. In addition, POR overexpression in HL-60 cells significantly compromised ATRA-induced cell proliferation inhibition, cell cycle arrest, differentiation and apoptosis, whereas downregulation of POR significantly potentiated ATRA effects. CONCLUSIONS: Our study therefore suggested that POR played an important role in regulating ATRA efficacy and CYP26A1 expression in HL-60 cells. PMID- 27366898 TI - Total Magnetic Resonance Imaging Burden of Small Vessel Disease in Cerebral Amyloid Angiopathy: An Imaging-Pathologic Study of Concept Validation. AB - IMPORTANCE: Cerebral amyloid angiopathy (CAA) is characteristically associated with magnetic resonance imaging (MRI) biomarkers of small vessel brain injury, including strictly lobar cerebral microbleeds, cortical superficial siderosis, centrum semiovale perivascular spaces, and white matter hyperintensities. Although these neuroimaging markers reflect distinct pathophysiologic aspects in CAA, no studies to date have combined these structural imaging features to gauge total brain small vessel disease burden in CAA. OBJECTIVES: To investigate whether a composite score can be developed to capture the total brain MRI burden of small vessel disease in CAA and to explore whether this score contributes independent and complementary information about CAA severity, defined as intracerebral hemorrhage during life or bleeding-related neuropathologic changes. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, cross-sectional study examined a single-center neuropathologic CAA cohort of eligible patients from the Massachusetts General Hospital from January 1, 1997, through December 31, 2012. Data analysis was performed from January 2, 2015, to January 9, 2016. Patients with pathologic evidence of CAA (ie, any presence of CAA from routinely collected brain biopsy specimen, biopsy specimen at hematoma evacuation, or autopsy) and available brain MRI sequences of adequate quality, including T2-weighted, T2* weighted gradient-recalled echo, and/or susceptibility-weighted imaging and fluid attenuated inversion recovery sequences, were considered for the study. MAIN OUTCOMES AND MEASURES: Brain MRIs were rated for lobar cerebral microbleeds, cortical superficial siderosis, centrum semiovale perivascular spaces, and white matter hyperintensities. All 4 MRI lesions were incorporated into a prespecified ordinal total small vessel disease score, ranging from 0 to 6 points. Associations with severity of CAA-associated vasculopathic changes (fibrinoid necrosis and concentric splitting of the wall), clinical presentation, number of intracerebral hemorrhages, and other imaging markers not included in the score were explored using logistic and ordinal regression. RESULTS: In total, 105 patients with pathologically defined CAA were included: 52 with autopsies, 22 with brain biopsy specimens, and 31 with pathologic samples from hematoma evacuations. The mean (range) age of the patients was 73 (71-74) years, and 55 (52.4%) were women. In multivariable ordinal regression analysis, severity of CAA associated vasculopathic changes (odds ratio, 2.40; 95% CI, 1.06-5.45; P = .04) and CAA presentation with symptomatic intracerebral hemorrhage (odds ratio, 2.23; 95% CI, 1.07-4.64; P = .03) were independently associated with the total MRI small vessel disease score. The score was associated with small, acute, diffusion weighted imaging lesions and posterior white matter hyperintensities in adjusted analyses. CONCLUSIONS AND RELEVANCE: This study provides evidence of concept validity of a total MRI small vessel disease score in CAA. After further validation, this approach can be potentially used in prospective clinical studies. PMID- 27366900 TI - Exclusive Bilateral Internal Thoracic Artery Grafts for Myocardial Revascularization Requiring Four Anastomoses or More: Outcomes from a Single Center Experience. AB - Introduction Multivessel coronary artery bypass graft (CABG) with bilateral internal thoracic arteries (BITA) has only been uncommon and technically demanding. We describe our experience with BITA only CABGs requiring >= 4 anastomoses. Material and Methods The department's database was queried for patients undergoing isolated CABG with >= 4 anastomoses. The surgical technique included systematically a right internal thoracic artery (ITA) of left ITA Y graft. The multivariate model included variables with a p < 0.3 at univariate analysis. Results Between January 2006 and December 2009, 251 consecutive patients (71 +/- 10 years) (on-pump: 130, off-pump: 121) had CABG with >= 4 anastomoses, representing 21% of total isolated CABGs for the same period; all patients received a totally arterial BITA only revascularization. Follow-up was 4.9 +/- 1.6 years. Overall and cardiac cumulative survivals were 78 and 92%, respectively, at 5 years. The occurrence of any major postoperative complication was associated with overall and cardiac mortality (odds ratio [OR]: 3.6, 95% confidence interval [CI]: 1.3-9.9 and OR: 5.4, 95% CI: 1.3-21.9, respectively). Major sternal wound complication requiring surgical revision was not associated with impaired glucose control (n = 9; diabetics: 6/82, 7.3%; nondiabetics: 3/169, 1.8%, p = 0.06). Preoperative kidney failure was associated with incomplete revascularization (OR: 6.2; 95% CI: 1.2-33.5), that was unfailingly due to ungraftable right coronary artery targets. Discussion BITA only revascularization was a valuable and safe procedure, with favorable results in terms of morbidity and mortality at a 5 years' follow-up. PMID- 27366901 TI - Reproducibility of quantitative indices of lung function and microstructure from 129 Xe chemical shift saturation recovery (CSSR) MR spectroscopy. AB - PURPOSE: To evaluate the reproducibility of indices of lung microstructure and function derived from 129 Xe chemical shift saturation recovery (CSSR) spectroscopy in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD), and to study the sensitivity of CSSR-derived parameters to pulse sequence design and lung inflation level. METHODS: Preliminary data were collected from five volunteers on three occasions, using two implementations of the CSSR sequence. Separately, three volunteers each underwent CSSR at three different lung inflation levels. After analysis of these preliminary data, five COPD patients were scanned on three separate days, and nine age-matched volunteers were scanned three times on one day, to assess reproducibility. RESULTS: CSSR-derived alveolar septal thickness (ST) and surface-area-to-volume (S/V) ratio values decreased with lung inflation level (P < 0.001; P = 0.057, respectively). Intra-subject standard deviations of ST were lower than the previously measured differences between volunteers and subjects with interstitial lung disease. The mean coefficient of variation (CV) values of ST were 3.9 +/- 1.9% and 6.0 +/- 4.5% in volunteers and COPD patients, respectively, similar to CV values for whole-lung carbon monoxide diffusing capacity. The mean CV of S/V in volunteers and patients was 14.1 +/- 8.0% and 18.0 +/- 19.3%, respectively. CONCLUSION: 129 Xe CSSR presents a reproducible method for estimation of alveolar septal thickness. Magn Reson Med 77:2107-2113, 2017. (c) 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID- 27366903 TI - The annexin A2 system and angiogenesis. AB - The formation of new blood vessels from pre-existing vasculature, the process known as angiogenesis, is highly regulated by pro- and anti-angiogenic signaling molecules including growth factors and proteases. As an endothelial cell-surface co-receptor for plasminogen and tissue plasminogen activator, the annexin A2 (ANXA2) complex accelerates plasmin generation and facilitates fibrinolysis. Plasmin can subsequently activate a downstream proteolytic cascade involving multiple matrix metalloproteinases. Thus, in addition to maintaining blood vessel patency, the ANXA2 complex can also promote angiogenesis via its pro-fibrinolytic activity. The generation of ANXA2-deficient mice allowed us to first observe the pro-angiogenic role of ANXA2 in vivo. Further investigations have provided additional details regarding the mechanism for ANXA2 regulation of retinal and corneal angiogenesis. Other studies have reported that ANXA2 supports angiogenesis in specific tumor-related settings. Here, we summarize results from in vivo studies that illustrate the pro-angiogenic role of ANXA2, and discuss the critical questions that may lead to an advanced understanding of the molecular mechanisms for ANXA2-mediated angiogenesis. Finally, highlights from studies on ANXA2-interacting agents offer potential therapeutic opportunities for the application of ANXA2-centered pharmaceuticals in angiogenesis-related disorders. PMID- 27366902 TI - Computer-assisted design, synthesis, binding and cytotoxicity assessments of new 1-(4-(aryl(methyl)amino)butyl)-heterocyclic sigma 1 ligands. AB - In this work we applied a blend of computational and synthetic techniques with the aim to design, synthesize, and characterize new sigma1 receptor (sigma1R) ligands. Starting from the structure of previously reported, high-affinity benzoxazolone-based sigma1 ligands, the three-dimensional homology model of the sigma1R was exploited for retrieving the molecular determinants to fulfill the optimal pharmacophore requirements. Accordingly, the benzoxazolone moiety was replaced by other heterocyclic scaffolds, the relevant conformational space in the sigma1R binding cavity was explored, and the effect on sigma1R binding affinity was ultimately assessed. Next, the compounds designed in silico were synthesized, and their affinity and selectivity toward sigma1 and sigma2 receptors were tested. Finally, a representative series of best sigma1R binders were assayed for cytotoxic activity on the SH-SY5Y human neuroblastoma cell line. Specifically, the new 4-phenyloxazolidin-2-one derivatives 2b (i.e., (R)-2b and (S)-2b) emerged as potential leads for further development as sigma1R agents, as they were found endowed with the highest sigma1R affinity (Kisigma1 values in the range 0.95-9.3 nM), and showed minimal cytotoxic levels exhibited in the selected, cell-based test, in line with a sigma1R agonist behavior. PMID- 27366904 TI - Emerging functions as host cell factors - an encyclopedia of annexin-pathogen interactions. AB - Emerging infectious diseases and drug-resistant infectious agents call for the development of innovative antimicrobial strategies. With pathogenicity now considered to arise from the complex and bi-directional interplay between a microbe and the host, host cell factor targeting has emerged as a promising approach that might overcome the limitations of classical antimicrobial drug development and could open up novel and efficient therapeutic strategies. Interaction with and modulation of host cell membranes is a recurrent theme in the host-microbe relationship. In this review, we provide an overview of what is currently known about the role of the Ca2+ dependent, membrane-binding annexin protein family in pathogen-host interactions, and discuss their emerging functions as host cell derived auxiliary proteins in microbe-host interactions and host cell targets. PMID- 27366905 TI - Novel Mechanisms of Compromised Lymphatic Endothelial Cell Homeostasis in Obesity: The Role of Leptin in Lymphatic Endothelial Cell Tube Formation and Proliferation. AB - Leptin is a hormone produced by adipose tissue that regulates various physiological processes. Recent studies have shown that the level of circulating leptin is elevated in obese patients and have suggested a relationship between obesity and postoperative lymphedema. However, the mechanisms by which postoperative lymphedema develops in obese patients and the mechanisms by which leptin regulates lymphatic endothelial cell homeostasis such as tube formation and cell proliferation remain unknown. Here we report that leptin regulates tube formation and cell proliferation in human dermal lymphatic endothelial cells (HDLECs) by activation of the signal transducer and activator of transcription 3 pathway, which is downstream signaling of the leptin receptor. Additionally, we found that upregulation of suppressor of cytokine signaling 3 underlies the mechanisms by which a high dose of leptin inhibits cell proliferation and tube formation. Leptin also enhanced expression of the proinflammatory cytokine IL-6 in HDLECs. Interestingly, IL-6 rescues the compromised cell proliferation and tube formation caused by treatment with a high dose of leptin in an autocrine or paracrine manner. Taken together, our findings reveal a novel mechanism by which compromised HDLECs maintain their homeostasis during inflammation mediated by leptin and IL-6. Thus, regulating the level of leptin or IL-6 may be a viable strategy to reduce the incidence of postoperative lymphedema. PMID- 27366907 TI - Reputation Effects in Social Networks Do Not Promote Cooperation: An Experimental Test of the Raub & Weesie Model. AB - Despite the popularity of the notion that social cohesion in the form of dense social networks promotes cooperation in Prisoner's Dilemmas through reputation, very little experimental evidence for this claim exists. We address this issue by testing hypotheses from one of the few rigorous game-theoretic models on this topic, the Raub & Weesie model, in two incentivized lab experiments. In the experiments, 156 subjects played repeated two-person PDs in groups of six. In the "atomized interactions" condition, subjects were only informed about the outcomes of their own interactions, while in the "embedded" condition, subjects were informed about the outcomes of all interactions in their group, allowing for reputation effects. The design of the experiments followed the specification of the RW model as closely as possible. For those aspects of the model that had to be modified to allow practical implementation in an experiment, we present additional analyses that show that these modifications do not affect the predictions. Contrary to expectations, we do not find that cooperation is higher in the embedded condition than in the atomized interaction. Instead, our results are consistent with an interpretation of the RW model that includes random noise, or with learning models of cooperation in networks. PMID- 27366906 TI - Hepatitis C Virus Core Protein Promotes miR-122 Destabilization by Inhibiting GLD 2. AB - The liver-specific microRNA miR-122, which has essential roles in liver development and metabolism, is a key proviral factor for hepatitis C virus (HCV). Despite its crucial role in the liver and HCV life cycle, little is known about the molecular mechanism of miR-122 expression regulation by HCV infection. Here, we show that the HCV core protein downregulates the abundance of miR-122 by promoting its destabilization via the inhibition of GLD-2, a non-canonical cytoplasmic poly(A) polymerase. The decrease in miR-122 expression resulted in the dysregulation of the known functions of miR-122, including its proviral activity for HCV. By high-throughput sequencing of small RNAs from human liver biopsies, we found that the 22-nucleotide (nt) prototype miR-122 is modified at its 3' end by 3'-terminal non-templated and templated nucleotide additions. Remarkably, the proportion of miR-122 isomers bearing a single nucleotide tail of any ribonucleotide decreased in liver specimens from patients with HCV. We found that these single-nucleotide-tailed miR-122 isomers display increased miRNA activity and stability over the 22-nt prototype miR-122 and that the 3'-terminal extension is catalyzed by the unique terminal nucleotidyl transferase activity of GLD-2, which is capable of adding any single ribonucleotide without preference of adenylate to the miR-122 3' end. The HCV core protein specifically inhibited GLD 2, and its interaction with GLD-2 in the cytoplasm was found to be responsible for miR-122 downregulation. Collectively, our results provide new insights into the regulatory role of the HCV core protein in controlling viral RNA abundance and miR-122 functions through miR-122 stability modulation. PMID- 27366908 TI - Temperature-Related Yield Constraints of Early-Rice in South China: A Cross Location Analysis. AB - Warm temperature during post-heading is generally hypothesized to be the critical factor limiting grain yield of early-rice in South China. However, there is no direct evidence to confirm this hypothesis in the field. This study was conducted to determine the temperature-related yield constraints of early-rice in South China. Field experiments were carried out in Huaiji (a location in South China) and Changsha (a location in the Yangtze River basin) in 2011-2013. In each year, two rice cultivars were grown in early-rice growing season in Huaiji and in single-rice growing season in Changsha. Huaiji had higher average daily maximum temperature during post-heading than Changsha. The higher temperature during post heading induced early plant senescence (slower crop growth rate and shorter grain filling duration), but grain weight did not reduce because it was compensated for by increased translocation of pre-heading biomass. The higher temperature during post-heading also did not cause a reduction in grain filling percentage. Huaiji had lower temperature during pre-heading than Changsha, which to some extent resulted in slower crop growth rate and consequently lower biomass production and smaller sink size in Huaiji than in Changsha. As a result, grain yield was about 30% lower in Huaiji than in Changsha. Our results indicate that grain yield of early-rice in South China is limited not by warm temperature during post-heading but partially by cool temperature during pre-heading, and suggest that enhancing sink size and meanwhile maintaining good translocation of pre-heading biomass may be an effective way to achieve high yield for early-rice in South China. PMID- 27366909 TI - Association between Dietary Patterns and Cardiovascular Risk Factors among Middle Aged and Elderly Adults in Taiwan: A Population-Based Study from 2003 to 2012. AB - BACKGROUND: Cardiovascular disease (CVD) is one of the leading causes of mortality and loss of disability-adjusted life years in developed countries. This study derived a dietary pattern using an a priori method and additionally derived dietary patterns using a posteriori methods, and assessed the relationship with CVD risk factors in Taiwanese middle-aged and elderly adults. METHODS: Cross sectional analyses of 62,965 subjects aged 40 years and above from the Mei Jau (MJ) database collected between 2003 and 2012 in Taiwan. Diet was assessed using a 22 item semi-quantitative food frequency questionnaire. Using this information, three dietary patterns were generated. The a priori diet was labeled the Taiwanese dietary pattern and was derived using hypothesized effect of 22 food groups, while two a posteriori dietary patterns, "vegi-fruits" and "meat processed", were derived using principal component analysis. The association between dietary patterns and a range of CVD risk factors (i.e. blood lipids, blood glucose and C-reactive protein) was evaluated using linear regression. RESULTS: The results showed that high intake (Q5, quintile 5) of Taiwanese diet was negatively associated with CVD risk factors at (p < 0.001, model 3), but not with triacylglycerol. In addition, high intake of vegi-fruit dietary pattern (Q5) was negatively associated with CVD risk factors (p < 0.001), but not with high density lipoprotein, while high consumption of meat-processed dietary pattern (Q5) was positively associated with CVD risk factors (p < 0.001), but negatively related with triacylglycerol in Q3 level and no association with C-reactive protein. CONCLUSION: A negative association was observed between Taiwanese or vegi-fruit dietary patterns and CVD risk factors, while a positive association was found between meat-processed dietary pattern and CVD risk factors. The findings suggested that a diet rich in vegetables and fruits has a beneficial effect in the management of CVD risk factors. PMID- 27366911 TI - Strong Solvent Effects on the Nonlinear Optical Properties of Z and E isomers from Azo-Enaminone Derivatives. AB - We calculated the nonlinear optical properties of 24 azo-enaminone derivatives, incorporating solvent effects on their geometric and elec-tronic structure, to assess the impact of the environment on these properties. Namely, we incorporated chloroform, tetrahydrofuran, acetone, ethanol, methanol, dimethyl sulfoxide on our calculations and compared our results incorporating solvent effects with our gas phase calculations. To account for the electron correlation effects on NLO properties, the calculations were performed at MP2/6-31G(p)//MP2/6-31G(d) level set. The Polarizable Continuum Model (PCM) was used to simulate the presence of the solvent. The exponents of p extra functions added to heavy atoms were obtained, imposing the maximization of the first hyperpolarizability. Two structural configurations (Z and E) of azo-enaminones were investigated to assess the isomeric effects of the electric properties. Our results show that both solvent polarity and relative strength of the donor groups have significant impact on the electric properties, but more strikingly on the first hyperpolarizability beta. PMID- 27366910 TI - A Novel, Unbiased Analysis Approach for Investigating Population Dynamics: A Case Study on Calanus finmarchicus and Its Decline in the North Sea. AB - Marine populations are controlled by a series of drivers, pertaining to both the physical environment and the biological environment (trophic predator-prey interactions). There is heated debate over drivers, especially when trying to understand the causes of major ecosystem events termed regime shifts. In this work, we have researched and developed a novel methodology based on Genetic Programming (GP) for distinguishing which drivers can influence species abundance. This methodology benefits of having no a priori assumptions either on the ecological parameters used or on the underlying mathematical relationships among them. We have validated this methodology applying it to the North Sea pelagic ecosystem. We use the target species Calanus finmarchicus, a key copepod in temperate and subarctic ecosystems, along with 86 biological, hydrographical and climatic time series, ranging from local water nutrients and fish predation, to large scale climate pressure patterns. The chosen study area is the central North Sea, from 1972 to 2011, during which period there was an ecological regime shift. The GP based analysis identified 3 likely drivers of C. finmarchicus abundance, which highlights the importance of considering both physical and trophic drivers: temperature, North Sea circulation (net flow into the North Atlantic), and predation (herring). No large scale climate patterns were selected, suggesting that when there is availability of both data types, local drivers are more important. The results produced by the GP based procedure are consistent with the literature published to date, and validate the use of GP for interpreting species dynamics. We propose that this methodology holds promises for the highly non-linear field of ecology. PMID- 27366912 TI - Cu(OAc)2-Mediated Cascade Annulation of Diarylalkyne Sulfonamides through Dual C N Bond Formation: Synthesis of 5,10-Dihydroindolo[3,2-b]indoles. AB - An unusual cascade reaction featuring annulation of diarylalkyne sulfonamides to form 5,10-dihydroindolo[3,2-b]indoles has been realized with Cu(OAc)2 as the sole oxidant. This unprecedented process encompasses two sequential C-N bond formations, allowing for an efficient synthesis of the biologically important indoloindole derivatives. PMID- 27366913 TI - Screening Oligosaccharide Libraries against Lectins Using the Proxy Protein Electrospray Ionization Mass Spectrometry Assay. AB - An electrospray ionization mass spectrometry (ESI-MS) assay for screening carbohydrate libraries against lectins is described. The assay is based on the proxy protein ESI-MS method, which combines direct ESI-MS protein-ligand binding measurements and competitive protein binding, to simultaneously detect and quantify protein-carbohydrate interactions. Specific interactions between components of the library and the target protein (PT) are identified from changes in the relative abundances (as measured by ESI-MS) of the carbohydrate complexes of a proxy protein (Pproxy), which binds to all components of the library with known affinity, upon addition of PT to the solution. The magnitude of the change in relative abundance of a given Pproxy-ligand complex provides a quantitative measure of the affinity of the corresponding PT-ligand interaction. A mathematical framework for the implementation of the method in the case of monovalent (single binding site) Pproxy and monovalent and multivalent (multiple equivalent and independent binding sites) PT is described. The application of the method to screen small libraries of oligosaccharides, on the basis of human histo blood group antigens and milk oligosaccharides, against an N-terminal fragment of the family 51 carbohydrate-binding module, a fucose-binding lectin from Ralstonia solanacearum, and human norovirus VA387 P particle (24-mer of the protruding domain of the capsid protein), serves to demonstrate the reliability and versatility of the assay. PMID- 27366914 TI - Editorial. PMID- 27366915 TI - Imidazolium-Based Porous Organic Polymers: Anion Exchange-Driven Capture and Luminescent Probe of Cr2O7(2.). AB - A series of imidazolium-based porous organic polymers (POP-Ims) was synthesized through Yamamoto reaction of 1,3-bis(4-bromophenyl)imidazolium bromide and tetrakis(4-bromophenyl)ethylene. Porosities and hydrophilicity of such polymers may be well tuned by varying the ratios of two monomers. POP-Im with the highest density of imidazolium moiety (POP-Im1) exhibits the best dispersity in water and the highest efficiency in removing Cr2O7(2-). The capture capacity of 171.99 mg g(-1) and the removal efficiency of 87.9% were achieved using an equivalent amount of POP-Im1 within 5 min. However, no Cr2O7(2-) capture was observed using nonionic analogue despite its large surface area and abundant pores, suggesting that anion exchange is the driving force for the removal of Cr2O7(2-). POP-Im1 also displays excellent enrichment ability and remarkable selectivity in capturing Cr2O7(2-). Cr(VI) in acid electroplating wastewater can be removed completely using excess POP-Im1. In addition, POP-Im1 can serve as a luminescent probe for Cr2O7(2-) due to the incorporation of luminescent tetraphenylethene moiety. PMID- 27366918 TI - To Appear in CHEMICAL REVIEWS, Vol. 99, No. 10. PMID- 27366916 TI - Theoretical Analysis on the Importance of Achiral Unidentate Ligands to Electronic Circular Dichroism of cis-Bis(ethylenediamine) Cobalt(III) Complexes. AB - Compared with the importance of didentate ligands to chiral chelates, little is known about the influence of unidentate ligands on the chiroptical properties of related chelates. To assess the importance of achiral unidentate ligands to electronic circular dichroism (ECD) spectra, calculations of the excitation energies and oscillator and rotational strengths for all the Lambda-enantiomers of bis(ethylenediamine) cobalt(III) complexes cis-[Co(en)2(X)2](n+) (X = Cl(-), CN(-), NH3, N3(-), NO2(-), H2O; n = 1, 3) were performed at the TDDFT/B3LYP/6 311++G(2d,p)//DFT/B3LYP/6-311++G(2d,p) level of theory, including solvent effects. The individual contributions of the chiral arrays, Delta/Lambda octahedral core, delta/lambda twists of the en ligands, and delta/lambda relative orientations of the unidentate ligands to the rotational strengths of related transitions were quantitatively determined and graphically presented. It was found that, for the chelates with nonaxially symmetric unidentate ligands (N3(-), NO2(-), H2O), the chiral orientation (delta/lambda) of the unidentate ligands not only dominates the ECD spectra of the Lambda-diastereoisomers but also dominates the relative energies in solution with the delta-orientation preferred. For those complexes with axially symmetric unidentate ligands (Cl(-), CN(-), NH3), the inherent dissymmetry within the metal ion-donor atom cluster was found to be unidentate ligand-dependent. The Boltzmann-weighted averaged ECD spectra of the complexes with Lambda-octahedral core are in excellent agreement with the observed ones, except that for the diazido complex, they are opposite in sign. This demonstrates that the absolute configuration of the complex cis-(-) [Co(en)2(N3)2](+) is Delta, not the Lambda-form assigned by McCaffery et al. in 1965. These findings not only reveal the importance of unidentate ligands to the ECD spectra of related chelates but also provide an insight for the influence of unidentate ligands on both the inherent dissymmetry and the distributional chirality. PMID- 27366919 TI - Conformations of Prolyl-Peptide Bonds in the Bradykinin 1-5 Fragment in Solution and in the Gas Phase. AB - The dynamic nature of intrinsically disordered peptides makes them a challenge to characterize by solution-phase techniques. In order to gain insight into the relation between the disordered state and the environment, we explore the conformational space of the N-terminal 1-5 fragment of bradykinin (BK[1-5](2+)) in the gas phase by combining drift tube ion mobility, cold-ion spectroscopy, and first-principles simulations. The ion-mobility distribution of BK[1-5](2+) consists of two well-separated peaks. We demonstrate that the conformations within the peak with larger cross-section are kinetically trapped, while the more compact peak contains low-energy structures. This is a result of cis-trans isomerization of the two prolyl-peptide bonds in BK[1-5](2+). Density-functional theory calculations reveal that the compact structures have two very different geometries with cis-trans and trans-cis backbone conformations. Using the experimental CCSs to guide the conformational search, we find that the kinetically trapped species have a trans-trans configuration. This is consistent with NMR measurements performed in a solution, which show that 82% of the molecules adopt a trans-trans configuration and behave as a random coil. PMID- 27366920 TI - Organoarsenical Biotransformations by Shewanella putrefaciens. AB - Microbes play a critical role in the global arsenic biogeocycle. Most studies have focused on redox cycling of inorganic arsenic in bacteria and archaea. The parallel cycles of organoarsenical biotransformations are less well characterized. Here we describe organoarsenical biotransformations in the environmental microbe Shewanella putrefaciens. Under aerobic growth conditions, S. putrefaciens reduced the herbicide MSMA (methylarsenate or MAs(V)) to methylarsenite (MAs(III)). Even though it does not contain an arsI gene, which encodes the ArsI C-As lyase, S. putrefaciens demethylated MAs(III) to As(III). It cleaved the C-As bond in aromatic arsenicals such as the trivalent forms of the antimicrobial agents roxarsone (Rox(III)), nitarsone (Nit(III)) and phenylarsenite (PhAs(III)), which have been used as growth promoters for poultry and swine. S. putrefaciens thiolated methylated arsenicals, converting MAs(V) into the more toxic metabolite monomethyl monothioarsenate (MMMTAs(V)), and transformed dimethylarsenate (DMAs(V)) into dimethylmonothioarsenate (DMMTAs(V)). It also reduced the nitro groups of Nit(V), forming p-aminophenyl arsenate (p arsanilic acid or p-AsA(V)), and Rox(III), forming 3-amino-4 hydroxybenzylarsonate (3A4HBzAs(V)). Elucidation of organoarsenical biotransformations by S. putrefaciens provides a holistic appreciation of how these environmental pollutants are degraded. PMID- 27366921 TI - Oral Chinese herbal medicine versus placebo for psoriasis vulgaris: A systematic review. AB - OBJECTIVES: Psoriasis is a chronic inflammatory skin disorder and the efficacy and safety of Chinese herbal medicine (CHM) treatments is unclear. This review evaluates oral CHM for psoriasis vulgaris clinical trial evidence. DESIGN: The Cochrane Library, PubMed, EMBASE, CINAHL, AMED, CBM, CNKI, CQVIP and Wanfang databases were searched from inception to June 2015. Randomised controlled trials (RCTs) of oral CHM compared to placebo data were included and analysed using Review Manager 5.2. RESULTS: Seven studies were included, no study utilised identical CHM intervention. Four studies data were subgrouped (decoction or capsule/pill) and pooled in meta-analysis to evaluate treatment effective rate for PASI60 or above (RR: 2.74 [0.92, 8.21] I2 = 65%). Another five studies were subgrouped and evaluated for PASI score change, (MD -7.00 [-10.74, -3.27] I2 = 98%). Only one study presented Dermatology Life Quality Index data, which favoured CHM (MD: -4.08 [-7.56, -0.60]). Two studies presented data on psoriasis related inflammatory cell-signalling protein tumour necrosis factor-a (TNF-a) (MD: -4.92 [-5.31, -4.53]). No serious adverse events were reported. CONCLUSION: While CHMs appear to be safe and may have benefit for psoriasis, variation between CHM interventions, outcome measures and the quality of included studies limit the conclusions of this review. Further rigorous RCTs utilising reliable, validated symptom and QoL outcome measures are recommended. PMID- 27366922 TI - Certolizumab pegol for treating axial spondyloarthritis. AB - INTRODUCTION: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease of the spine and sacroiliac (SI) joints. The spectrum of axSpA includes ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA). Evidence has supported the use of TNF alpha inhibitors (TNFi) in treating these diseases, with good efficacy and tolerable safety profiles. Certolizumab pegol (CZP) is an anti TNF alpha (TNFa) agent with data to support its use in both AS and nr-axSpA. AREAS COVERED: The pharmacologic properties of CZP were reviewed. Data regarding the use and efficacy of CZP in axSpA were reviewed. Quality of life outcomes and safety profiles of CZP in axSpA patients were discussed as well. EXPERT OPINION: While there are several biologics with evidence for improved outcomes in AS, there is less evidence for biologic medications that have good efficacy in nr axSpA. CZP has good evidence of improved outcomes in terms of clinical efficacy, patient reported outcomes and imaging outcomes in both conditions, with a tolerable safety profile. PMID- 27366923 TI - Pyramiding PvPGIP2 and TAXI-III But Not PvPGIP2 and PMEI Enhances Resistance Against Fusarium graminearum. AB - Plant protein inhibitors counteract the activity of cell wall-degrading enzymes (CWDEs) secreted by pathogens to breach the plant cell-wall barrier. Transgenic plants expressing a single protein inhibitor restrict pathogen infections. However, since pathogens secrete a number of CWDEs at the onset of infection, we combined more inhibitors in a single wheat genotype to reinforce further the cell wall barrier. We combined polygalacturonase (PG) inhibiting protein (PGIP) and pectin methyl esterase inhibitor (PMEI), both controlling the activity of PG, one of the first CWDEs secreted during infection. We also pyramided PGIP and TAXI III, a xylanase inhibitor that controls the activity of xylanases, key factors for the degradation of xylan, a main component of cereal cell wall. We demonstrated that the pyramiding of PGIP and PMEI did not contribute to any further improvement of disease resistance. However, the presence of both pectinase inhibitors ensured a broader spectrum of disease resistance. Conversely, the PGIP and TAXI-III combination contributed to further improvement of Fusarium head blight (FHB) resistance, probably because these inhibitors target the activity of different types of CWDEs, i.e., PGs and xylanases. Worth mentioning, the reduction of FHB symptoms is accompanied by a reduction of deoxynivalenol accumulation with a foreseen great benefit to human and animal health. PMID- 27366924 TI - Recyclable Strategy for the Production of High-Purity Galacto-oligosaccharides by Kluyveromyces lactis. AB - A recyclable strategy for the production of high-purity (>95%) galacto oligosaccharides (GOS) was developed using Kluyveromyces lactis in both the synthesis and purification steps. For the synthesis of GOS, ethanol-permeabilized cells (p-cells) of K. lactis were used because the enhanced permeability facilitated the mass transfer of the substrate and the release of oligosaccharide products. For the purification of GOS, non-permeabilized K. lactis cells (np cells) were preferred as a result of their intrinsic cell membrane barrier toward GOS, which led to the selective consumption of carbohydrate. In this way, undesired glucose, galactose, and lactose in the raw GOS solution can be completely removed. This strategy is recyclable not only because of the high stability and reusability of p-cells and np-cells but also because the ethanol, which is simultaneously generated during the purification, can be reused for the preparation of p-cells. The strategy proposed in this study is a promising candidate for the efficient production of high-purity GOS. PMID- 27366925 TI - Relationships among Sensory Responsiveness, Anxiety, and Ritual Behaviors in Children with and without Atypical Sensory Responsiveness. AB - AIM: To explore relationships between sensory responsiveness, anxiety, and ritual behaviors in boys with typical and atypical sensory responsiveness. METHOD: Forty eight boys, ages 5-9 participated in the study (28 boys with atypical sensory responsiveness and 20 controls). Atypical sensory responsiveness was defined as a score of <=154 on the Short Sensory Profile. Parents completed the Sensory Profile, the Screen for Child Anxiety Related Emotional Disorders, and the Childhood Routines Inventory. RESULTS: Children with atypical sensory responsiveness had significantly higher levels of anxiety and a higher frequency of ritual behaviors than controls. Atypical sensory responsiveness was significantly related to both anxiety and ritual behaviors, with anxiety mediating the relationship between sensory modulation and ritual behaviors. CONCLUSIONS: The findings elucidate the potential consequences of atypical sensory responsiveness and could support the notion that ritual behaviors develop as a coping mechanism in response to anxiety stemming from primary difficulty in modulating sensory input. PMID- 27366926 TI - "Not Homeless Yet. I'm Kind of Couch Surfing": Finding Identities for People at a Homeless Shelter. AB - The meanings of homelessness are fluid and socially constructed, providing resources and limitations for individuals to negotiate their identities and relationships in everyday life. In this study, we examine the strategies and corresponding resources utilized by people who are homeless to cope with the labeling of a homeless identity and to redefine their identities. We used constant comparative analysis to examine in-depth interviews with 16 participants (male = 11, female = 5) who access a local homeless shelter in the southwest United States for resources. We identified three strategies that homeless people adopt to cope with the labeling of homeless identity: (a) differentiating oneself from others who are homeless, (b) prioritizing certain aspects of life, and (c) embracing the status of homelessness. Although these strategies have been identified in previous literature, the authors extend this line of research by identifying the common resources people who are homeless utilize when adopting these strategies, which entail important implications for theory development and practical implications. PMID- 27366927 TI - Detection of suspected small bowel bleeding: challenges and controversies. AB - INTRODUCTION: Detection of small bowel (SB) bleeding remains a challenge to gastroenterologists, with a dearth of standardized recommendations regarding evaluation and management. Areas covered: A recursive literature search was performed using PubMed, Cochrane and Medline databases for original and review articles on SB and obscure gastrointestinal bleeding (OGIB). Based upon the available literature, this review outlines the main challenges and controversies, and provides a practical and cost-effective approach towards SB bleeding. Expert commentary: SB bleeding is suspected in patients with persistent or recurrent bleeding after negative bidirectional endoscopy, and unexplained iron deficiency anemia. Selection of test(s) should be individualized based upon patient presentation and suspicion for type of underlying lesion. Endoscopic or radiologic evaluation and treatment is the mainstay in the majority of patients, while pharmacologic agents may have a role in patients with refractory bleeding, and those unable to undergo evaluation. PMID- 27366928 TI - Risk of obesity in male shift workers: A chronophysiological approach. AB - AIMS: Why are some healthy male shift workers (SWers) overweight [body mass index (BMI) >25 and <30] if not obese (BMI >30)? Seven risk factors potentially causing overweight and obesity were evaluated, namely (1) age, (2) physical/sports activity, (3) length of exposure to shift work (SW), (4) speed of shift rotation, (5) tolerance to SW, (6) internal desynchronization of circadian rhythms and (8) night eating (nocturnal nibbling). "New" as well as "old" data, acquired from longitudinal and individual time series of 5-56 days recording span, were reanalyzed. The data were analyzed from a set of field studies of 67 SWers and 53 non-shift workers (non-SWers). To estimate the respective weight of these factors, a multiple regression analysis (MRA) was used among other statistical tools. A similar age-related increase in BMI was validated (with p < 0.001) in both SWers and non-SWers. However, in SWers, desynchronization of rhythms increases the effect of age on BMI. Length of exposure to SW, tolerance to SW and speed of rotation do not seem to play a role as risk factors. Major effects are likely to relate to a sedentary lifestyle (lack of regular physical or sport activities) (MRA with p < 0.01), as well as, presumably, to a nocturnal nibbling of carbohydrates, which mimics the night eating syndrome. PMID- 27366930 TI - Imprinting defects in osteosarcoma: DNA- and chromatin-modifying drugs hold promise for osteosarcoma therapy. PMID- 27366931 TI - Fine particulate speciation profile and emission factor of municipal solid waste incinerator established by dilution sampling method. AB - In this study, fine particulate matter (PM2.5) emitted from a municipal solid waste incinerator (MSWI) was collected using dilution sampling method. Chemical compositions of the collected PM2.5 samples, including carbon content, metal elements, and water-soluble ions, were analyzed. Traditional in-stack hot sampling was simultaneously conducted to compare the influences of dilution on PM2.5 emissions and the characteristics of the bonded chemical species. The results, established by a dilution sampling method, show that PM2.5 and total particulate matter (TPM) emission factors were 61.6 +/- 4.52 and 66.1 +/- 5.27 g ton-waste(-1), respectively. The average ratio of PM2.5/TPM is 0.93, indicating that more than 90% of PM emission from the MSWI was fine particulate. The major chemical species in PM2.5 included organic carbon (OC), Cl(-), NH4(+), elemental carbon (EC) and Si, which account for 69.7% of PM2.5 mass. OC was from the unburned carbon in the exhaust, which adsorbed onto the particulate during the cooling process. High Cl(-) emission is primarily attributable to wastes containing plastic bags made of polyvinyl chloride, salt in kitchen refuse and waste biomass, and so on. Minor species that account for 0.01-1% of PM2.5 mass included SO4(2-), K(+), Na, K, NO3(-), Al, Ca(2+), Zn, Ca, Cu, Fe, Pb, and Mg. The mean ratio of dilution method/in-stack hot method was 0.454. The contents of water-soluble ions (Cl(-), SO4(2-), NO3(-)) were significantly enriched in PM2.5 via gas-to-particle conversion in the dilution process. Results indicate that in stack hot sampling would underestimate levels of these species in PM2.5. IMPLICATIONS: PM2.5 samples from a municipal solid waste incinerator (MSWI) were collected simultaneously by a dilution sampling technique and a traditional in stack method. PM2.5 emission factors and chemical speciation profiles were established. Dilution sampling provides more reliable data than in-stack hot sampling. The results can be applied to estimate the PM2.5 emission inventories of MSWI, and the source profile can be used for contribution estimate of chemical mass balance modeling. PMID- 27366929 TI - Regions of variable DNA methylation in human placenta associated with newborn neurobehavior. AB - The placenta regulates the in utero environment and functionally impacts fetal development. Candidate gene studies identified variation in placental DNA methylation is associated with newborn neurologic and behavioral outcomes including movement quality, lethargic behavior, attention, and arousal. We sought to identify novel regions of variable DNA methylation associated with newborn attention, lethargy, quality of movement, and arousal by performing an epigenome wide association study in 335 infants from a US birth cohort. Methylation status was quantified using the Illumina HumanMethylation450 BeadChip array and associations to newborn outcomes assessed by the NICU Network Neurobehavioral Scales (NNNS) were identified while incorporating established bioinformatics algorithms to control for confounding by cell type composition. Methylation of CpGs within FHIT (cg15970800) and ANKRD11 (cg16710656) demonstrated genome-wide significance (P < 1.8 * 10(-7)) in specific associations with infant attention. CpGs whose differential methylation was associated with all 4 neurobehavioral outcomes were common to 50 genes involved in biological processes relating to cellular adhesion and nervous system development. Comprehensive methylation profiling identified relationships between methylation of FHIT and ANKRD11, which have been previously linked to neurodevelopment and behavioral outcomes in genetic association studies. Subtle changes in DNA methylation of these genes within the placenta may impact normal variation of a newborn's ability to alter and track visual and auditory stimuli. Gene ontology analysis suggested that those genes with variable methylation related to these outcomes are over represented in biological pathways involved in brain development and placental physiology, supportive of our hypothesis for a key role of the placenta in neurobehavioral outcomes. PMID- 27366932 TI - Dietary Patterns and Risk of Esophageal Cancer Mortality: The Japan Collaborative Cohort Study. AB - Several case-control studies have associated dietary patterns with esophageal cancer (EC) risk, but prospective studies are scarce. We investigated dietary pattern and EC mortality risk associations by smoking status. Participants were 26,562 40- to 79-yr-old Japanese men, who enrolled in the Japan Collaborative Cohort Study between 1988 and 1990. Hazard ratios (HRs) and 95% confidence intervals (CIs) for EC mortality in nonsmokers and smokers were estimated using Cox proportional models. During follow-up (1988-2009), 132 participants died of EC. Using a baseline food frequency questionnaire and factor analysis, vegetable, animal, and dairy product food patterns were identified. EC risk decreased significantly with a higher factor score for the dairy product pattern (Ptrend = 0.042) and was more pronounced in smokers [multivariable HR (4th vs. 1st quartiles) = 0.57, 95% CI: 0.30, 1.09; Ptrend = 0.021]. Neither vegetable nor animal food patterns were significant overall; however, EC risk increased with a higher factor score for the animal food pattern in nonsmokers [multivariable HR (4th vs. 1st quartiles) = 6.01, 95% CI: 1.17, 30.88; Ptrend = 0.021], although the small number of events was a limitation. Our findings suggest a dairy product pattern may reduce EC risk in Japanese men, especially smokers. PMID- 27366933 TI - Comparison between the TRS-398 code of practice and the TG-51 dosimetry protocol for flattening filter free beams. AB - Dosimetry protocols for external beam radiotherapy currently in use, such as the IAEA TRS-398 and AAPM TG-51, were written for conventional linear accelerators. In these accelerators, a flattening filter is used to produce a beam which is uniform at water depths where the ionization chamber is used to measure the absorbed dose. Recently, clinical linacs have been implemented without the flattening filter, and published theoretical analysis suggested that with these beams a dosimetric error of order 0.6% could be expected for IAEA TRS-398, because the TPR20,10 beam quality index does not accurately predict the stopping power ratio (water to air) for the softer flattening-filter-free (FFF) beam spectra. We measured doses on eleven FFF linacs at 6 MV and 10 MV using both dosimetry protocols and found average differences of 0.2% or less. The expected shift due to stopping powers was not observed. We present Monte Carlo k Q calculations which show a much smaller difference between FFF and flattened beams than originally predicted. These results are explained by the inclusion of the added backscatter plates and build-up filters used in modern clinical FFF linacs, compared to a Monte Carlo model of an FFF linac in which the flattening filter is removed and no additional build-up or backscatter plate is added. PMID- 27366934 TI - Material specificity of memory deficits in children with temporal tumors and seizures: A case series. AB - In adults, left temporal lobe pathology is typically associated with verbal memory deficits, whereas right temporal lobe pathology is thought to produce visual memory deficits in right-handed individuals. However, in children and adolescents with temporal lobe pathology, conclusions regarding material specificity of memory deficits remain unclear. The goal of the present case series is to examine the profile of verbal and visual memory impairment in children with temporal lobe tumors. Three patients with identified right temporal tumors and three patients with left temporal tumors are included. The Wide Range Assessment of Memory and Learning-Second Edition (WRAML-2) was administered as part of a larger neuropsychological battery. As anticipated, participants with right temporal lesions showed impaired visual memory relative to intact verbal memory. Interestingly, although the discrepancies between verbal and visual indices were less extreme, those with left temporal lesions showed a similar memory profile. These seemingly counterintuitive findings among left temporal tumor patients likely reflect less hemispheric specialization in children in comparison to adults and the fact that early developmental lesions in the left hemisphere may lead to functional reorganization of language-based skills. PMID- 27366935 TI - Designing molecular complexes using free-energy derivatives from liquid-state integral equation theory. AB - Complex formation between molecules in solution is the key process by which molecular interactions are translated into functional systems. These processes are governed by the binding or free energy of association which depends on both direct molecular interactions and the solvation contribution. A design goal frequently addressed in pharmaceutical sciences is the optimization of chemical properties of the complex partners in the sense of minimizing their binding free energy with respect to a change in chemical structure. Here, we demonstrate that liquid-state theory in the form of the solute-solute equation of the reference interaction site model provides all necessary information for such a task with high efficiency. In particular, computing derivatives of the potential of mean force (PMF), which defines the free-energy surface of complex formation, with respect to potential parameters can be viewed as a means to define a direction in chemical space toward better binders. We illustrate the methodology in the benchmark case of alkali ion binding to the crown ether 18-crown-6 in aqueous solution. In order to examine the validity of the underlying solute-solute theory, we first compare PMFs computed by different approaches, including explicit free-energy molecular dynamics simulations as a reference. Predictions of an optimally binding ion radius based on free-energy derivatives are then shown to yield consistent results for different ion parameter sets and to compare well with earlier, orders-of-magnitude more costly explicit simulation results. This proof-of-principle study, therefore, demonstrates the potential of liquid state theory for molecular design problems. PMID- 27366936 TI - Thermal Recycling of Brominated Flame Retardants with Fe2O3. AB - Plastics containing brominated flame retardants (BFRs) constitute the major fraction of nonmetallic content in e-waste. Co-pyrolysis of BFRs with hematite (Fe2O3) represents a viable option for the thermal recycling of BFRs. Consensus of experimental findings confirms the excellent bromine fixation ability of Fe2O3 and the subsequent formation of iron bromides. This contribution provides a comprehensive mechanistic account of the primary reactions between a cluster model of Fe2O3 and major bromine-bearing products from the decomposition of tetrabromobisphenol A (TBBA), the most commonly deployed BFR. We estimate the thermo-kinetic parameters for interactions of Fe2O3 with HBr, brominated alkanes and alkenes, bromobenzene, and bromophenol. Dissociative addition of HBr at a Fe O bond proceeds through a trivial barrier of 8.2 kcal/mol with fitted parameters in the Arrhenius equation of k(T) = 7.96 * 10(11) exp(-6400/RT) s(-1). The facile and irreversible nature for HBr addition to Fe2O3 accords with the experimentally reported 90% reduction in HBr emission when Fe2O3 interacts with TBBA pyrolysates. A detailed kinetic analysis indicates that, transformation of Fe2O3 into iron bromides and oxybromides occurs via successive addition of HBr to Fe(Br)-O(H) entities. Elimination of a water molecule proceeds through an intramolecular H transfer. A direct elimination one-step mechanism operates in the dehydrohalogenation of bromoethane into ethene over Fe2O3. Dissociative decomposition and direct elimination channels assume comparable reaction rates in formation of acetylene from vinyl bromide. Results from this study provide an atomic-based insight into a promising thermal recycling route of e-waste. PMID- 27366937 TI - Quantitative Index of the Relative Ease of Formation and sigma-Bonding Strength of N-Heterocyclic Carbenes. AB - An energy-based index of the ease of N-heterocyclic carbene (NHC) formation either by deprotonation of precursor salts to give neutral NHCs or deprotonation of heterocyclic mesomeric betaines to give anionic NHCs is described. This index (CREF; Carbene Relative Energy of Formation), which is easily calculated using DFT methods, also gives a quantitative measure of the relative sigma-donor strength of NHCs. CREF index values for a wide range of known and unknown NHC ring systems are reported and their significance discussed. PMID- 27366938 TI - beta-Alkyl Elimination: Fundamental Principles and Some Applications. AB - This review describes organometallic compounds and materials that are capable of mediating a rarely encountered but fundamentally important reaction: beta-alkyl elimination at the metal-Calpha-Cbeta-R moiety, in which an alkyl group attached to the Cbeta atom is transferred to the metal or to a coordinated substrate. The objectives of this review are to provide a cohesive fundamental understanding of beta-alkyl-elimination reactions and to highlight its applications in olefin polymerization, alkane hydrogenolysis, depolymerization of branched polymers, ring-opening polymerization of cycloalkanes, and other useful organic reactions. To provide a coherent understanding of the beta-alkyl elimination reaction, special attention is given to conditions and strategies used to facilitate beta alkyl-elimination/transfer events in metal-catalyzed olefin polymerization, which provide the well-studied examples. PMID- 27366939 TI - An estimate of the public health impact and cost-effectiveness of universal vaccination with a 9-valent HPV vaccine in Germany. AB - INTRODUCTION: Since 2007, the German Standing Vaccination Committee recommends HPV vaccination for girls aged 12-17 with a 2- (Cervarix(r)) or 4-valent (Gardasil(r)) vaccine. A 9-valent vaccine (Gardasil 9(r)) recently received a European market authorization in 2015. METHODS: A dynamic transmission model was calibrated to the German setting and used to estimate costs and QALYs associated with vaccination strategies. RESULTS: Compared to the current vaccination program, the 9-valent vaccine extended to boys shows further reductions of 24% in the incidence of cervical cancer, 30% and 14% in anal cancer for males and females, as well as over a million cases of genital warts avoided after 100 years. The new strategy is associated with an ICER of 22,987? per QALY gained, decreasing to 329? when considering the vaccine switch for girls-only. CONCLUSION: Universal vaccination with the 9-valent vaccine can yield significant health benefits when compared to the current program. PMID- 27366940 TI - Analysis of homo- and hetero-dimerization among the three 6-phosphogluconate dehydrogenase isoforms of Arabidopsis. AB - We recently described that all three 6-phosphogluconate dehydrogenase (6PGDH) isoforms of Arabidopsis (PGD) with similar length show dual localization: PGD1 and PGD3 in the cytosol and in plastids, and PGD2 in the cytosol and in peroxisomes. We set out to investigate heterodimer formation, however due to only weak homodimerization of all Arabidopsis PGD isoforms in yeast cells, we conducted further protein-protein interaction studies in planta to investigate homomer versus heteromer formation and their sub-cellular localization. Bimolecular fluorescence complementation (BiFC) analyses in co-transfected Arabidopsis protoplasts demonstrated that all PGD isoforms may form homo- and heterodimers. Notably, with free N-terminal ends, PGD1-PGD3 heterodimers were detected both in the cytosol and in the plastid stroma, but heterodimers with PGD2 only in the cytosol. This independently confirmed that PGD2 cannot enter plastids. On the other hand, with free C-terminal ends, PGD1-PGD2 and PGD3-PGD2 heterodimers were confined to the cytosol, indicating that only PGD2 homodimers are imported by peroxisomes. Together these findings suggest functional redundancy of PGD1 and PGD3 inside plastids, and relevance of PGD1-PGD2 or PGD3 PGD2 heterodimer formation in the cytosol: this could retain sufficient 6PGDH activity needed for NADPH provision, especially during stress defense and initiation of developmental responses. PMID- 27366941 TI - Discovery of Novel Thiophene-Based, Thumb Pocket 2 Allosteric Inhibitors of the Hepatitis C NS5B Polymerase with Improved Potency and Physicochemical Profiles. AB - The hepatitis C viral proteins NS3/4A protease, NS5B polymerase, and NS5A are clinically validated targets for direct-acting antiviral therapies. The NS5B polymerase may be inhibited directly through the action of nucleosides or nucleotide analogues or allosterically at a number of well-defined sites. Herein we describe the further development of a series of thiophene carboxylate allosteric inhibitors of NS5B polymerase that act at the thumb pocket 2 site. Lomibuvir (1) is an allosteric HCV NS5B inhibitor that has demonstrated excellent antiviral activity and potential clinical utility in combination with other direct acting antiviral agents. Efforts to further explore and develop this series led to compound 23, a compound with comparable potency and improved physicochemical properties. PMID- 27366942 TI - Analysis of iodine-131-induced early thyroid hormone variations in Graves' disease. AB - OBJECTIVE: This prospective study aimed to assess iodine-131 (I)-induced early thyroid hormone variations in Graves' disease (GD) and determine the associated factors. MATERIALS AND METHODS: One hundred and seventy-one GD patients treated with I were evaluated (47 men, 124 women). I was administered at 9.0+/-4.9 mCi on average. Serum free triiodothyronine and free thyroxin were measured within 24 h before treatment and 8 (3-14) days after treatment. Patients were divided into increase, no change, and decrease groups, respectively, on the basis of hormone variations after treatment. chi-Test, analysis of variance, and the Kruskal Wallis test were used to compare groups in terms of sex, age, course of disease, thyroid stimulating hormone receptor antibodies, antithyroid drug (ATD) pretreatment time, time of ATD discontinuation before I treatment, 24 h thyroid I uptake, thyroid weight, I activity, and I activity/thyroid weight (MUCi/g). The Spearman method was used for correlation analyses. RESULTS: Twenty-seven, 20, and 124 cases were assigned to increase, no change, and decrease groups, respectively. Significant differences were found among groups in the time of ATD discontinuation before I treatment [the median duration for methimazole was 11 (5 26), 16 (10-30), and 21 (1-30) days, P=0.000, the median duration for propylthiouracil was 12.5 (5-24), 22 (11-26), and 26 (21-30) days, P=0.000], thyroid weight (93.5+/-33.6, 90.3+/-48.8, and 74.1+/-26.0 g, P=0.003), and MUCi/g (84.8+/-11.8, 100.4+/-24.9, and 121.1+/-44.0 MUCi/g, P=0.000). Interestingly, MUCi/g was negatively and positively correlated to the possibility of hormone increase and decrease, respectively. No significant differences were found in the other parameters assessed. CONCLUSION: At the early stage of I treatment for GD, few patients showed increased thyroid hormone levels. Key factors may include time of ATD discontinuation before I treatment and MUCi/g. High MUCi/g might decrease thyroid hormone levels in early treatment, making it safe. PMID- 27366943 TI - A pan-cancer analysis of MYC-PVT1 reveals CNV-unmediated deregulation and poor prognosis in renal carcinoma. AB - The PVT1 lncRNA has recently been involved in tumorigenesis by affecting the protein stability of the MYC proto-oncogene. Both MYC and PVT1 reside in a well known cancer-risk locus and enhanced levels of their products have been reported in different human cancers. Nonetheless, the extension and relevance of the MYC PVT1 deregulation in tumorigenesis has not yet been systematically addressed.Here we performed a pan-cancer analysis of matched copy number, transcriptomic, methylation, proteomic and clinicopathological profiles for almost 7000 patients from 17 different cancers represented in the TCGA cohorts. Among all cancers types, kidney renal clear cell carcinoma (KIRC) showed the strongest upregulation of PVT1 and increased levels of both MYC and PVT1 correlated with the clinical outcome. PVT1 misregulation in KIRC is mostly associated to promoter hypomethylation rather than locus amplification. Furthermore, we found an association between MYC levels and PVT1 expression, which impacted on MYC-target genes.Collectively, our study discloses the role of PVT1 as a novel prognostic factor and as a molecular target for novel therapeutic interventions in renal carcinoma. PMID- 27366944 TI - Basal autophagy is pivotal for Hodgkin and Reed-Sternberg cells' survival and growth revealing a new strategy for Hodgkin lymphoma treatment. AB - As current classical Hodgkin lymphoma (cHL) treatment strategies have pronounced side-effects, specific inhibition of signaling pathways may offer novel strategies in cHL therapy. Basal autophagy, a regulated catabolic pathway to degrade cell's own components, is in cancer linked with both, tumor suppression or promotion. The finding that basal autophagy enhances tumor cell survival would thus lead to immediately testable strategies for novel therapies. Thus, we studied its contribution in cHL.We found constitutive activation of autophagy in cHL cell lines and primary tissue. The expression of key autophagy-relevant proteins (e.g. Beclin-1, ULK1) and LC3 processing was increased in cHL cells, even in lymphoma cases. Consistently, cHL cells exhibited elevated numbers of autophagic vacuoles and intact autophagic flux. Autophagy inhibition with chloroquine or inactivation of ATG5 induced apoptosis and reduced proliferation of cHL cells. Chloroquine-mediated inhibition of basal autophagy significantly impaired HL growth in-vivo in NOD SCID gammac-/- (NSG) mice. We found that basal autophagy plays a pivotal role in sustaining mitochondrial function.We conclude that cHL cells require basal autophagy for growth, survival and sustained metabolism making them sensitive to autophagy inhibition. This suggests basal autophagy as useful target for new strategies in cHL treatment. PMID- 27366945 TI - Transcriptomic reappraisal identifies MGLL overexpression as an unfavorable prognosticator in primary gastrointestinal stromal tumors. AB - The role of deregulated cellular metabolism, particularly lipid metabolism, in gastrointestinal stromal tumors (GISTs) remains unclear. Through data mining of published transcriptomes, we examined lipid metabolism-regulating drivers differentially upregulated in high-risk cases and identified monoglyceride lipase (MGLL) as the top-ranking candidate involved in GIST progression. MGLL expression status was examined in three GIST cell lines and two independent sets of primary localized GISTs. MGLL mRNA abundance and immunoexpression was determined in 70 cases through the QuantiGene assay and H-scoring on whole sections, respectively. H-scoring was extended to another cohort for evaluating MGLL immunoexpression on tissue microarrays, yielding 350 informative cases, with KIT/PDGFRA mutation genotypes noted in 213 of them. Both imatinib-sensitive (GIST882) and -resistant (GIST48 and GIST430) cell lines exhibited increased MGLL expression. MGLL mRNA levels significantly increased from adjacent normal tissue to the non-high-risk group (p = 0.030) and from the non-high-risk group to high-risk GISTs (p = 0.012), and were associated with immunoexpression levels (p < 0.001, r = 0.536). MGLL overexpression was associated with the nongastric location (p = 0.022) and increased size (p = 0.017), and was strongly related to mitosis and risk levels defined by NIH and NCCN criteria (all p <= 0.001). Univariately, MGLL overexpression was strongly predictive of poorer disease-free and overall survival (both p < 0.001), which remained prognostically independent for both endpoints, along with higher risk levels. Conclusively, MGLL is a lipid metabolic enzyme causatively implicated in GIST progression given its association with unfavorable clincopathological factors and independent negative prognostic effects. PMID- 27366946 TI - IGF2-derived miR-483 mediated oncofunction by suppressing DLC-1 and associated with colorectal cancer. AB - Emerging evidence indicates that IGF2 plays an important role in various human malignancies, including colorectal cancer (CRC). Hsa-miR-483 is located within intron 7 of the IGF2 locus. However, the mechanism by which increased IGF2 induces carcinogenesis remains largely elusive. DLC-1 has been identified as a candidate tumor suppressor. In this study, we aimed at investigating whether miR 483 transcription is IGF2-dependent, identifying the functional target of miR 483, and evaluating whether tissue and serum miR-483-3p or miR-483-5p levels are associated with CRC. Our results showed that sequences upstream miR-483 had undetectable promoter activity and levels of IGF2, miR-483-3p, and miR-483-5p were synchronously increased in CRC tissues. Positive correlations between IGF2 and miR-483-3p (r=0.4984, ***p<0.0001), and between IGF2 and miR-483-5p (r=0.6659, ***p<0.0001) expression were found. In addition, patients with CRC had a significantly higher serum miR-483-5p level (*p<0.05) compared to normal controls. DLC-1 expression was decreased in colorectal cancer tissues and diminished through transient transfection with miR-483-3p. Our results suggest that IGF2 may exert its oncofunction, at least partly, through its parasitic miR 483 which suppressed DLC-1 in CRC cells. Thus, miR-483 might serve as a new target for therapy and a potential biomarker for the detection of colorectal cancer. PMID- 27366947 TI - The anti-tumor efficacy of 3-(2-Nitrophenyl) propionic acid-paclitaxel (NPPA PTX): a novel paclitaxel bioreductive prodrug. AB - Hypoxia is an important microenvironmental pressure present in the majority of solid tumors and, so, tumor hypoxia might be considered an attractive target for tumor therapy. One strategy for targeting hypoxia is to develop bioreductive prodrugs. In the present research, we synthesized a bioreductive paclitaxel prodrug, 3-(2-Nitrophenyl) propionic acid-paclitaxel (NPPA-PTX). The stability of NPPA-PTX in PBS and rat plasma was investigated. The anti-tumor activity of NPPA PTX was also evaluated in vitro and in vivo. The results of our stability study indicated that NPPA-PTX was stable in PBS and rat plasma as well as in the blood circulation. The in vitro and in vivo anti-tumor activity of NPPA-PTX was confirmed in both KB cells and MDA-MB-231 cells. Our results also indicated that NPPA-PTX could completely convert to active PTX in tumor tissues and produced the anti-tumor activity in both KB and MDA-MB-231 tumor-bearing nude mice. We suggest that the dissociated PTX which converted from NPPA-PTX in tumor tissues played a key role in producing anti-tumor activity. Considering all our results, we suggest that NPPA-PTX is a novel bioreductive PTX prodrug which could undergo further evaluation. PMID- 27366948 TI - Combined genetic and epigenetic interferences with interferon signaling expose prostate cancer cells to viral infection. AB - Interferons (IFNs) induce anti-viral programs, regulate immune responses, and exert anti-proliferative effects. To escape anti-tumorigenic effects of IFNs, malignant cells attenuate JAK/STAT signaling and expression of IFN stimulated genes (ISGs). Such attenuation may enhance the susceptibility of tumor cells to oncolytic virotherapy. Here we studied genetic and epigenetic mechanisms of interference with JAK/STAT signaling and their contribution to susceptibility of prostate cancer cells to viral infection. Bioinformatics analysis of gene expression in cohorts of prostate cancer patients revealed genetic and epigenetic interference with the IFN program. To correlate lack of IFN signaling and susceptibility to viral infection and oncolysis; we employed LNCaP prostate cancer cells as cellular model, and the human metapneumovirus and the epizootic hemorrhagic disease virus as infectious agents. In LNCaP cells, JAK1 is silenced by bi-allelic inactivating mutations and epigenetic silencing, which also silences ISGs. Chemical inhibition of epigenetic silencing partially restored IFN sensitivity, induced low levels of expression of selected ISGs and attenuated, but failed to block, viral infection and oncolysis. Since viral infection was not blocked by epigenetic modifiers, and these compounds may independently-induce anti-tumor effects, we propose that epigenetic modifiers and virotherapy are compatible in treatment of prostate tumors defective in JAK1 expression and IFN signaling. PMID- 27366949 TI - Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis. AB - Proliferator-activated receptor gamma (PPARgamma) activation can result in transcription of proteins involved in oxidative stress defence and mitochondrial biogenesis which could rescue mitochondrial dysfunction in Parkinson's disease (PD).The PPARgamma agonist pioglitazone is protective in models of PD; however side effects have limited its clinical use. The cannabinoid Delta9 tetrahydrocannabinol (Delta9-THC) may have PPARgamma dependent anti-oxidant properties. Here we investigate the effects of Delta9-THC and pioglitazone on mitochondrial biogenesis and oxidative stress. Differentiated SH-SY5Y neuroblastoma cells were exposed to the PD relevant mitochondrial complex 1 inhibitor 1-methyl-4-phenylpyridinium iodide (MPP+). We found that only Delta9 THC was able to restore mitochondrial content in MPP+ treated SH-SY5Y cells in a PPARgamma dependent manner by increasing expression of the PPARgamma co-activator 1alpha (PGC-1alpha), the mitochondrial transcription factor (TFAM) as well as mitochondrial DNA content. Co-application of Delta9-THC with pioglitazone further increased the neuroprotection against MPP+ toxicity as compared to pioglitazone treatment alone. Furthermore, using lentiviral knock down of the PPARgamma receptor we showed that, unlike pioglitazone, Delta9-THC resulted in a PPARgamma dependent reduction of MPP+ induced oxidative stress. We therefore suggest that, in contrast to pioglitazone, Delta9-THC mediates neuroprotection via PPARgamma dependent restoration of mitochondrial content which may be beneficial for PD treatment. PMID- 27366950 TI - ERK1/2/MAPK pathway-dependent regulation of the telomeric factor TRF2. AB - Telomere stability is a hallmark of immortalized cells, including cancer cells. While the telomere length is maintained in most cases by the telomerase, the activity of a protein complex called Shelterin is required to protect telomeres against unsuitable activation of the DNA damage response pathway. Within this complex, telomeric repeat binding factor 2 (TRF2) plays an essential role by blocking the ataxia telangiectasia-mutated protein (ATM) signaling pathway at telomeres and preventing chromosome end fusion. We showed that TRF2 was phosphorylated in vitro and in vivo on serine 323 by extracellular signal regulated kinase (ERK1/2) in both normal and cancer cells. Moreover, TRF2 and activated ERK1/2 unexpectedly interacted in the cytoplasm of tumor cells and human tumor tissues. The expression of non-phosphorylatable forms of TRF2 in melanoma cells induced the DNA damage response, leading to growth arrest and tumor reversion. These findings revealed that the telomere stability is under direct control of one of the major pro-oncogenic signaling pathways (RAS/RAF/MEK/ERK) via TRF2 phosphorylation. PMID- 27366952 TI - [Surgical Treatment of Acetabulum Fractures with a New Acetabulum Butterfly Plate]. AB - Introduction: There have been significant increases in the number of acetabular fractures in elderly patients with primarily ventral pathology and medial protrusion of the femoral head. We have developed the "acetabulum wing plate", which is designed to facilitate repositioning, with its anatomically precontoured structure, and which offers full support of the quadrilateral surface, thus counteracting the force of the femoral head pushing inwards. Conventional plate osteosynthesis only provides insufficient support to the medial surface. After a successful series of biomechanical tests, we now report a clinical case series. Material and Methods: Between April 2012 and August 2013, a total of twelve patients underwent plate osteosynthesis using the precontoured plate described above. The patients (ten male, two female) were aged between 45 and 87 years, the average age being 62.5 years. We were able to perform all osteosynthesis with the modified Stoppa approach, in combination with the first window of the ilioinguinal approach (according to Letournel). In most patients, the plate was applied without complications, In some patients, it even supported repositioning. In six patients, the fractures were of the anterior collum and six fractures were fractures of both colla. The mean time span of follow-up was 13.1 months, the minimum being 4.5 and the maximum 23 months. Results: In most patients, the intra and postoperative computed tomographic scans showed anatomically correct placement of the plate, thus confirming the correct repositioning of the bone. Routine follow-ups are part of the hospital's postsurgical care system for acetabular fractures; these revealed no secondary dislocation or loosening of the plate. The radiological examination showed consolidation of the fractures after a mean period of twelve weeks. A full year after the initial procedure, no implant specific complications were observed. Revision surgery was necessary in one patient due to bleeding five days after surgery. In another patient, necrosis of the femoral head necessitated total hip replacement ten weeks after the first surgical intervention. In summary, the concept of the plate proved to be successful in its first case series. Summary: In spite of increasing surgical expertise and the refinements of standard approaches, there is a recognisable shift in acetabular fractures from mainly posterior fracture patterns to fractures of the anterior column. The new acetabulum wing plate takes these factors into account and is an implant designed to address the anterior aspects of the acetabulum. The outcome of the first application is promising and the acetabulum wing plate produces satisfactory results in our patients. PMID- 27366951 TI - Multifunctional near-infrared light-triggered biodegradable micelles for chemo- and photo-thermal combination therapy. AB - A combination of chemo- and photo-thermal therapy (PTT) has provided a promising efficient approach for cancer therapy. To achieve the superior synergistic chemotherapeutic effect with PTT, the development of a simple theranostic nanoplatform that can provide both cancer imaging and a spatial-temporal synchronism of both therapeutic approaches are highly desired. Our previous study has demonstrated that near-infrared (NIR) light-triggered biodegradable chitosan based amphiphilic block copolymer micelles (SNSC) containing light-sensitive 2 nitrobenzyl alcohol and NIR dye cypate on the hydrophobic block could be used for fast light-triggered drug release. In this study, we conjugated the SNSC micelles with tumor targeting ligand c(RGDyK) and also encapsulated antitumor drug Paclitaxel (PTX). The results show that c(RGDyK)-modified micelles could enhance the targeting and residence time in tumor site, as well as be capable performing high temperature response for PTT on cancer cells and two-photon photolysis for fast release of anticancer drugs under NIR irradiation. In vitro release profiles show a significant controlled release effort that the release concentration of PTX from micelles was significantly increased with the exposure of NIR light. In vitro and in vivo antitumor studies demonstrate that, compared with chemo or PTT treatment alone, the combined treatment with the local exposure of NIR light exhibited significantly enhanced anti-tumor efficiency. These findings indicate that this system exhibited great potential in tumor-targeting imaging and synchronous chemo- and photo-thermal therapy. PMID- 27366953 TI - [Midterm Results for Quality of Life After Surgical Treatment of Moore Type V Fractures of the Tibial Plateau]. AB - Background: Dislocation fractures of the tibial plateau often lead to functional restrictions and subjective complaints from the patients. Besides functional and radiological results, criteria to determine the quality of life are of increasing importance. Intermediate term restriction in quality of life was evaluated and correlated with objective radiological results in patients with Moore type V dislocation fracture of the tibial plateau. Patients and Methods: From 2003 to 2012, a multicentre retrospective cohort study in three hospitals was used to register 36 patients with 38 Moore type V dislocation fractures of the tibial plateau. The injury mechanism, the surgical treatment (one step or two step surgery, single or double plate fixation) the complication rate, the radiological result (Kellgren/Lawrence osteoarthritis score, loss of reduction, secondary deviation of the axis) after a mean follow-up of 37 months, and the quality of life (pain and function by NRS, IKDC form, EQ 5D score) after a mean follow-up of 68 months (range, 15-128 months), were analysed. Results: The mean age of the 27 men and the 9 women was 50.8 years. There were 30 cases of high impact injury. An external fixator was used for primary fracture stabilisation in 24 knees; definitive internal fixation was performed in a second step. Internal fixation using a single plate was used in 12 knees, and double plate fixation in 25 knees; one patient was treated definitively with an external fixator. Early complications (3 * infection, 2 * compartment syndrome, 4 * implant failure) were seen in 21.1 % of patients; all could be cured surgically. The function of the affected knee joint gave a mean NRS of 4.53; the IKDC score was 50.46, and the EQ 5D 7.47. Only two patients (5 %) were free of pain, 27 (75 %) reported mild to moderate pain, and 7 patients (20 %) reported severe pain. Four patients are retired or have applied for a pension. Altogether, the quality of life was calculated as being 44 % of the initial value before the injury. Four patients required an endoprosthetic replacement at an early stage, after an average of 6 months. Signs of osteoarthritis (Kellgren/Lawrence > I) were seen in 32 of the remaining 33 fractures; 19 of these exhibited distinct signs of osteoarthritis (Kellgren/Lawrence III, IV). Loss of reduction (>= 2 mm) was seen in 13 (34.2 %) and deviation of axis (> 10 degrees ) in 3 patients (7.8 %). There was no relation to the surgical strategy. However, there was a correlation between the subjective assessments of the quality of life and the radiological results. Conclusion: Moore type V dislocation fractures of the tibial plateau are severe knee injuries resulting in a distinct reduction in quality of life in the intermediate term. There is a correlation between the subjective assessments and the objective radiological results. Therefore, the congruency of the articular surface and the axis have to be reconstructed as precisely as possible when repairing fractures of the tibial plateau. PMID- 27366954 TI - Power seat function usage and wheelchair discomfort for power wheelchair users. AB - OBJECTIVES: To investigate correlations between power seat functions (PSFs) usage and wheelchair discomfort. DESIGN: Quasi-experimental design: Time series design. SETTING: In-home trial in participants' home/community. PARTICIPANTS: Thirteen power wheelchair users who independently used power wheelchairs equipped with PSFs as their primary means of mobility. MAIN OUTCOME MEASURES: PSF usage variables include the frequency of performing repositioning and using PSFs (tilt, recline, legrests and seat elevation), wheelchair occupancy, and driving distance. The Tool for Assessing Wheelchair disComfort (TAWC) were used to evaluate general discomfort and discomfort intensity. RESULTS: Spearman correlation coefficient showed that the frequency of using tilt, recline, and legrest is significantly correlated with discomfort intensity. Multiple regression analysis with backward stepwise indicated that these functions can explain 43.8% of the variance (R2 = .438, F(3,33) = 8.588, P < 0.01) in the discomfort intensity score. The best-first decision tree shows that the frequency of using the legrest function was the top node, followed by recline and tilt functions. The overall accuracy of prediction with ten-fold cross validation for discomfort intensity was 79.4%. CONCLUSIONS: For people who used power wheelchairs equipped with PSFs, correlation analysis and regression modeling provided evidence from the quantitative data that increasing the frequency of using PSFs may decrease wheelchair discomfort. Future studies should include interventions to encourage people to use their PSFs appropriately. PMID- 27366955 TI - Metal-Free [2 + 2 + 2] Cycloaddition of Ynamides with Nitriles to Construct 2,4 Diaminopyridines. AB - We present a metal-free [2 + 2 + 2] cycloaddition of ynamides with nitriles that enables highly efficient access to 2,4-diaminopyridines. This catalytic protocol is more environmentally friendly and allows for a concomitant construction of C-C and C-N bonds between ynamides and nitriles, exhibiting excellent chemoselectivity, regioselectivity, and wide functional groups tolerance. PMID- 27366956 TI - Reported History of Developmental Regression and Restricted, Repetitive Behaviors in Children with Autism Spectrum Disorders. AB - OBJECTIVE: Previous research on developmental regression in youth with autism spectrum disorders (ASD) has often been limited by the definition, assessment, and methodology used to evaluate and describe regression. This study sought to overcome these limitations by examining the prevalence, timing, and correlates of documented cases of developmental regression in a large, epidemiological sample of youth with ASD. METHOD: Utilizing a population-based surveillance methodology, this study includes 862 youth with ASD identified through abstraction and clinician record review. RESULTS: Approximately 21% of the sample had developmental regression documented in their medical or educational records with the mean age of regression being 24.2 +/- 14.3 months. Youth with ASD and a history of regression were more likely to have comorbid intellectual disability, a prior community diagnosis of ASD, and be eligible for educational services as a student with autism. Youth with a documented history of regression also had higher rates of restricted, repetitive behaviors, such as stereotyped speech, nonfunctional routines/rituals, and sensory interests. CONCLUSION: Results suggest that youth with a history of regression are not only more likely to have comorbid intellectual disability but are also are more likely to have been previously diagnosed with ASD in the community, suggesting that development regression may play an important role in identifying children who are at the risk for ASD and need evaluation. Higher rates of restricted, repetitive behaviors in youth with a documented history of regression may also provide important insights into the relationship between ASD and developmental regression. PMID- 27366957 TI - The Meaning of "Regression" in Children with Autism Spectrum Disorder: Why Does It Matter? PMID- 27366958 TI - Building Developmental-Behavioral Pediatrics in Low-Middle Income Countries Through International Collaboration. PMID- 27366959 TI - Adsorption of Amino Acids and Peptides on Metal and Oxide Surfaces in Water Environment: A Synthetic and Prospective Review. AB - Amino acids and peptides are often used as "model" segments of proteins for studying their behavior in various types of environments, and/or elaborating functional surfaces. Indeed, though the protein behavior is much more complex than that of their isolated segments, knowledge of the binding mode as well as of the chemical structure of peptides on metal or oxide surfaces is a significant step toward the control of materials in a biological environment. Such knowledge has considerably increased in the past few years, thanks to the combination of advanced characterization techniques and of modeling methods. Investigations of biomolecule-surface interactions in water/solvent environments are quite numerous, but only in a few cases is it possible to reach an understanding of the molecule-(water)-surface interaction with a level of detail comparable to that of the UHV studies. This contribution aims at reviewing the recent data describing the amino acid and peptide interaction with metal or oxide surfaces in the presence of water. PMID- 27366960 TI - Does the Stage of Keratoconus Affect Optical Coherence Tomography Measurements? AB - PURPOSE: To employ optical coherence tomography (OCT) to examine the relationship of changes in the retinal nerve fiber layer (RNFL) and macular thickness as well as ganglion cell (GC) parameters with the stage of keratoconus (KC), and to compare these changes with a control group. METHODS: A total of 84 eyes of 68 patients with KC and 29 eyes of 29 normal age-matched subjects underwent RNFL, macular thickness measurements, and ganglion cell analysis using Cirrus high definition (HD) OCT. Patients with KC were classified according to the Amsler Krumeich Classification. The measurements were analyzed in all quadrants for each KC stage and compared with control subjects. RESULTS: All RNFL, macular thickness, and ganglion cell parameters varied significantly among the groups (all p<0.001, analysis of variance). An increase in the stage of KC was correlated with decreased RNFL thickness, macular thickness, and ganglion cell parameters. CONCLUSIONS: RNFL, macular thicknesses, and ganglion cell parameters in all KC stages were lower than those in the control group. The RNFL, macular thickness, and ganglion cell parameters of the Grade 1 KC group were most similar to those of the control group. The severity of irregular astigmatism at the same stages of KC had a significant effect on OCT measurements. It may therefore be beneficial to know the amount of change/deviation in OCT measurements in keratoconus patients and to report which parameters exceed the standards so that OCT can be used to correlate the stage of keratoconus with the extent of the ocular disorder. PMID- 27366962 TI - Heavy Alcohol Use in the Couple Context: A Nationally Representative Longitudinal Study. AB - BACKGROUND: For young couples, a partner's heavy alcohol use may be a point of conflict and relationship distress, particularly when there are disparities in the severity of drinking across partners. OBJECTIVE: The aim was to examine the longitudinal impact of discrepancies in heavy alcohol use, particularly in couples with parenting responsibilities. METHODS: Data were obtained from 554 heterosexual couples (with at least one partner aged between 18 and 30 years of age) over two assessments from a well-established longitudinal study of Australian households. RESULTS: Multilevel analyses (examining time within partners within couples) indicated a high level of couple-level variation in individual reports of relationship satisfaction. Discrepancies in heavy alcohol use were negatively associated with relationship satisfaction over the assessment period and this was significantly moderated by parenthood. More specifically, heavy drinking discrepancies were associated with lower relationship satisfaction amongst parents more than nonparents. CONCLUSION: Among dissatisfied couples, managing discrepancies in alcohol use and helping heavy drinking partners may be an important intervention focus, particularly when providing professional support for young parents. PMID- 27366963 TI - Antibody drug conjugates: the future of chemotherapy? AB - PURPOSE OF REVIEW: The current review describes the rationale and current clinical development of antibody drug conjugates (ADCs), along with their perspectives for the future. RECENT FINDINGS: Trastuzumab emtansine was the first ADC approved by the U.S. Food and Drug Administration for the treatment of human epidermal growth factor receptor 2 positive metastatic breast cancer in the second-line setting, with a high efficacy and a favorable safety profile. ADC represents an exciting new class of cancer therapeutics that combines a targeted approach for delivering cytotoxic agents. About 30 new ADCs are currently under investigation in oncology. SUMMARY: ADCs are empowered antibodies designed to exploit the targeting ability of monoclonal antibodies (mAbs) by linking them to cytotoxic agents, giving them higher tumor selectivity, and potentially an increased therapeutic window, as compared with cytotoxic agents alone. The key components of ADCs include a mAb, a stable linker and a cytotoxic agent. In linking mAbs with cytotoxic agents, the aim is to optimize the properties of both components, bringing their complementary features together. Trastuzumab emtansine has been the first ADC to be marketed in human epidermal growth factor receptor 2 positive metastatic breast cancer. Current clinical development of ADCs includes a variety of targets, as well as combinations with other therapeutic agents, such as chemotherapy, radiotherapy, targeted therapies, and immune checkpoint inhibitors. PMID- 27366964 TI - Editorial. PMID- 27366961 TI - Methane-Oxidizing Enzymes: An Upstream Problem in Biological Gas-to-Liquids Conversion. AB - Biological conversion of natural gas to liquids (Bio-GTL) represents an immense economic opportunity. In nature, aerobic methanotrophic bacteria and anaerobic archaea are able to selectively oxidize methane using methane monooxygenase (MMO) and methyl coenzyme M reductase (MCR) enzymes. Although significant progress has been made toward genetically manipulating these organisms for biotechnological applications, the enzymes themselves are slow, complex, and not recombinantly tractable in traditional industrial hosts. With turnover numbers of 0.16-13 s( 1), these enzymes pose a considerable upstream problem in the biological production of fuels or chemicals from methane. Methane oxidation enzymes will need to be engineered to be faster to enable high volumetric productivities; however, efforts to do so and to engineer simpler enzymes have been minimally successful. Moreover, known methane-oxidizing enzymes have different expression levels, carbon and energy efficiencies, require auxiliary systems for biosynthesis and function, and vary considerably in terms of complexity and reductant requirements. The pros and cons of using each methane-oxidizing enzyme for Bio-GTL are considered in detail. The future for these enzymes is bright, but a renewed focus on studying them will be critical to the successful development of biological processes that utilize methane as a feedstock. PMID- 27366966 TI - The sleeping brain: Extenuating circumstances of the Marquis de La Fayette on October 6, 1789. PMID- 27366965 TI - Core-Shell-Shell NaYbF4:Tm@CaF2@NaDyF4 Nanocomposites for Upconversion/T2 Weighted MRI/Computed Tomography Lymphatic Imaging. AB - To circumvent the defects of different bioimaging techniques, the development of multifunctional probes for multimodality bioimaging is required. In the present study, a lanthanide-based core-shell-shell nanocomposite NaYbF4:Tm@CaF2@NaDyF4 composed of an ~9.5 nm NaYbF4:Tm nanocrystal as the core, ~2 nm CaF2 as the middle layer, and 1-2 nm NaDyF4 as the outermost shell was designed and synthesized. Following surface modification with the ligand, citrate acid, this nanocomposite was hydrophilic, emitted intense upconversion luminescence (UCL), and displayed a high X-ray computed tomography (CT) value of ~490 Hounsfield units (HU) and excellent r2 relaxivity of 41.1 mM(-1) s(-1). These results confirmed that the introduction of a middle CaF2 layer was necessary as a barrier to reduce cross-relaxation and the surface quenching effect, thus enhancing the upconversion emission of Tm(3+). This citrate-modified NaYbF4:Tm@CaF2@NaDyF4 nanocomposite was used as a multifunctional contrast agent for trimodal lymphatic bioimaging with T2-weighted magnetic resonance imaging (MRI), CT, and UCL imaging. The concept of fabricating a core-multishell nanostructure and the introduction of a Dy(3+)-based host as an outer layer is a useful strategy and can be used to develop a novel multifunctional nanoprobe for multimodality bioimaging. PMID- 27366967 TI - Modeling Tyrosinase Monooxygenase Activity. Spectroscopic and Magnetic Investigations of Products Due to Reactions between Copper(I) Complexes of Xylyl Based Dinucleating Ligands and Dioxygen: Aromatic Ring Hydroxylations and Irreversible Oxidation Products. PMID- 27366968 TI - Applied metabolomics in drug discovery. AB - INTRODUCTION: The metabolic profile is a direct signature of phenotype and biochemical activity following any perturbation. Metabolites are small molecules present in a biological system including natural products as well as drugs and their metabolism by-products depending on the biological system studied. Metabolomics can provide activity information about possible novel drugs and drug scaffolds, indicate interesting targets for drug development and suggest binding partners of compounds. Furthermore, metabolomics can be used for the discovery of novel natural products and in drug development. Metabolomics can enhance the discovery and testing of new drugs and provide insight into the on- and off target effects of drugs. AREAS COVERED: This review focuses primarily on the application of metabolomics in the discovery of active drugs from natural products and the analysis of chemical libraries and the computational analysis of metabolic networks. EXPERT OPINION: Metabolomics methodology, both experimental and analytical is fast developing. At the same time, databases of compounds are ever growing with the inclusion of more molecular and spectral information. An increasing number of systems are being represented by very detailed metabolic network models. Combining these experimental and computational tools with high throughput drug testing and drug discovery techniques can provide new promising compounds and leads. PMID- 27366969 TI - Crystal Structure of Amylomaltase from Corynebacterium glutamicum. AB - Amylomaltase is an essential enzyme in maltose utilization and maltodextrin metabolism, and it has been industrially used for the production of cyclodextrin and modification of starch. We determined the crystal structure of amylomaltase from Corynebacterium glutamicum (CgAM) at a resolution of 1.7 A. Although CgAM forms a dimer without NaCl, it exists as a monomer in physiological concentration of NaCl. CgAM is composed of N- and C-terminal domains, which can be further divided into two and four subdomains, respectively. It exhibits a unique structural feature at the functionally unknown N-domain and also shows two striking differences at the C-domain compared to other amylomaltases. These differences at extended edge of the substrate-binding site might affect substrate specificity for large cyclodextrin formation. The bis-tris methane and sulfate molecules bound at the substrate-binding site of our current structure mimic the binding of the hydroxyl groups of glucose bound at subsites -1 and -2, respectively. PMID- 27366970 TI - Effects of Extracellular Polymeric Substance Composition on Bacteria Disinfection by Monochloramine: Application of MALDI-TOF/TOF-MS and Multivariate Analysis. AB - In our previous study, we reported that the transport of monochloramine is affected by the extracellular polymeric substance (EPS) composition, which in turn affects the cell viability of both biofilm and detached clusters.11 However, although the transport and reaction of monochloramine in biofilm could be observed, the specific biomolecules reacting with the disinfectant and the mechanism of disinfection remains elusive. In this study, the impact of EPS composition on bacteria disinfection by monochloramine was qualitatively determined using both wild-type and isogenic mutant Pseudomonas strains with different EPS-secretion capacity and composition. To evaluate their EPS reactivity and contribution to susceptibility to monochloramine, we investigated the bacteria disinfection process using Fourier transform infrared spectroscopy (FTIR) and matrix-assisted laser desorption-ionization time-of-flight/time-of flight mass spectrometry (MALDI-TOF/TOF-MS). Canonical correlation analysis and partial least-squares regression modeling were employed to explore the changes that EPS underwent during the monochloramine disinfection process. The analyses results suggested significant reactions of the monochloramine with peptide fragments of proteins that are associated with carbohydrate utilization. Selected enzymes also showed different levels of inhibition by monochloramine when tested. PMID- 27366971 TI - Current process in hearing-aid fitting appointments: An analysis of audiologists' use of behaviour change techniques using the behaviour change technique taxonomy (v1). AB - OBJECTIVES: To observe and analyse the range and nature of behaviour change techniques (BCTs) employed by audiologists during hearing-aid fitting consultations to encourage and enable hearing-aid use. DESIGN: Non-participant observation and qualitative thematic analysis using the behaviour change technique taxonomy (version 1) (BCTTv1). STUDY SAMPLE: Ten consultations across five English NHS audiology departments. RESULTS: Audiologists engage in behaviours to ensure the hearing-aid is fitted to prescription and is comfortable to wear. They provide information, equipment, and training in how to use a hearing-aid including changing batteries, cleaning, and maintenance. There is scope for audiologists to use additional BCTs: collaborating with patients to develop a behavioural plan for hearing-aid use that includes goal-setting, action planning and problem-solving; involving significant others; providing information on the benefits of hearing-aid use or the consequences of non-use and giving advice about using prompts/cues for hearing-aid use. CONCLUSIONS: This observational study of audiologist behaviour in hearing-aid fitting consultations has identified opportunities to use additional behaviour change techniques that might encourage hearing-aid use. This information defines potential intervention targets for further research with the aim of improving hearing-aid use amongst adults with acquired hearing loss. PMID- 27366972 TI - Coronary CT angiography in clinical triage of patients at high risk of coronary artery disease. AB - OBJECTIVES: To test if cardiac computed tomography angiography (CCTA) can be used in the triage of patients at high risk of coronary artery disease. DESIGN: The diagnostic value of 64-detector CCTA was evaluated in 400 patients presenting with non-ST segment elevation myocardial infarction using invasive coronary angiography (ICA) as the reference method. The relation between the severity of disease by CCTA and a combined endpoint of death, re-hospitalization due to new myocardial infarction, or symptom-driven coronary revascularization was assessed. RESULTS: CCTA detects significant (>50%) coronary artery diameter stenosis with a sensitivity, specificity, and positive and negative predictive value of 99%, 81%, 96% and 95%, respectively. CCTA was used to triage patients into guideline defined treatment groups of "no or medical treatment", "referral to percutaneous coronary intervention" or to "coronary artery bypass graft surgery" and was compared to the index ICA. CCTA correctly triaged patients in 86% of cases. During a median follow-up of 50 months, the presence of an occluded artery by CCTA was associated with adverse outcome. CONCLUSION: CCTA has high diagnostic and prognostic value in patients with high likelihood of coronary artery disease and could, in theory, be used to triage high risk patients. As many obstacles remain, including logistical and safety issues, our study does not support the use of CCTA as an additional diagnostic test before ICA in an all-comer NSTEMI population. PMID- 27366973 TI - Completing a National Birth Cohort in the United States. PMID- 27366974 TI - The ion dependence of carbohydrate binding of CBM36: an MD and 3D-RISM study. AB - The molecular recognition process of the carbohydrate-binding module family 36 (CBM36) was examined theoretically. The mechanism of xylan binding by CBM36 and the role of Ca(2+) were investigated by the combined use of molecular dynamics simulations and the 3D reference interaction site model method. The CBM36 showed affinity for xylan after Ca(2+) binding, but not after Mg(2+) binding. Free energy component analysis of the xylan-binding process revealed that the major factor for xylan-binding affinity is the electrostatic interaction between the Ca(2+) and the hydroxyl oxygens of xylan. The van der Waals interaction between the hydrophobic side chain of CBM36 and the glucopyranose ring of xylan also contributes to the stabilization of the xylan-binding state. Dehydration on the formation of the complex has the opposite effect on these interactions. The affinity of CBM36 for xylan results from a balance of the interactions between the binding ion and solvents, hydrophilic residues around xylan, and the hydroxyl oxygens of xylan. When CBM binds Ca(2+), these interactions are well balanced; in contrast, when CBM binds Mg(2+), the dehydration penalty is excessively large. PMID- 27366975 TI - An unexpected rearrangement of pent-4-enofuranosides to cyclopentanones upon hydrogenolysis of the anomeric benzyl group. AB - During our synthesis toward the unique nucleoside antibiotic A201A, we were surprised to find that a benzyl arabino-pent-4-enofuranoside underwent a Ferrier II-like rearrangement readily to provide the corresponding cyclopentanone derivative in high yield and stereoselectivity upon hydrogenolysis of the anomeric benzyl group. PMID- 27366976 TI - Virus fitness differences observed between two naturally occurring isolates of Ebola virus Makona variant using a reverse genetics approach. AB - During the large outbreak of Ebola virus disease that occurred in Western Africa from late 2013 to early 2016, several hundred Ebola virus (EBOV) genomes have been sequenced and the virus genetic drift analyzed. In a previous report, we described an efficient reverse genetics system designed to generate recombinant EBOV based on a Makona variant isolate obtained in 2014. Using this system, we characterized the replication and fitness of 2 isolates of the Makona variant. These virus isolates are nearly identical at the genetic level, but have single amino acid differences in the VP30 and L proteins. The potential effects of these differences were tested using minigenomes and recombinant viruses. The results obtained with this approach are consistent with the role of VP30 and L as components of the EBOV RNA replication machinery. Moreover, the 2 isolates exhibited clear fitness differences in competitive growth assays. PMID- 27366977 TI - Landmark papers in cerebrovascular neurosurgery 2015. AB - The management of cerebrovascular disease has advanced considerably in 2015. Five randomized control trials have firmly established the role of endovascular thrombectomy for ischemic strokes due to large vessel occlusion. The randomized trial of intraarterial treatment for acute ischemic stroke (MR CLEAN) (Berkhemer et al. NEJM 2015;372:11-20) was the first of a series on the topic. There was a total of 5 randomized controlled trials published showing benefit in terms of functional outcomes at 90days for mechanical thrombectomy including the Endovascular Therapy for Ischemic stroke with perfusion-imaging selection (EXTEND IA) (Campbell et al. NEJM 2015;372:1009-18), the Randomized assessment of rapid endovascular treatment of ischemic stroke (ESCAPE) (Goyal et al. NEJM 2015;372:1019-30) trials, the stent-retriever thrombectomy after IV t-PA is t-PA alone in stroke (SWIFT-PRIME) (Saver et al. NEJM 2015;372:2285-95), and the thrombectomy within 8h after symptom onset in Ischemic stroke (REVASCAT) trial (Jovin et al. NEJM 2015; 372:2296-306). Six-year results from randomized controlled Barrow Ruptured Aneurysm Trial (BRAT) found no significant difference in functional outcomes in patients ruptured aneurysms treated surgically clippings versus endovascular treatment (Spetzler et al. JNS 2015;123:609-17. The 10-year results of the International Subarachnoid Aneurysm trial (ISAT) reported similar mortality rates and good functional outcomes between clipped and coiled patients (Molyneux et al. Lancet 2015;385:691-7). We also discuss the impact of genome wide sequencing studies in familial aneurysms, the largest publication on stent assisted coiling and flow diverter for aneurysms and noteworthy papers relevant to Moyamoya and cavernous malformations (Yang et al. Neurosurgery 2015;77:241-7). PMID- 27366978 TI - The Effect of Positional Support on Tolerance of Wakeful Prone in Infants. AB - : Supervised wakeful prone promotes motor milestones. Indications are that many infants do not receive adequate prone, with poor tolerance as a contributing factor. A common suggestion is the use of positional support. AIMS: This study has two main purposes: (1) To determine whether varied levels of positional support affect the duration of time spent in prone, and (2) to determine the effect of positional support with respect to infant size. METHODS: A convenience sample of 32 healthy infants ranging in size, aged 3.3 +/- 0.04 months, were placed in prone in three counterbalanced randomized levels of positional support: a flat blanket (Blanket condition), a rolled blanket (Roll condition), and a pillow (Boppy condition). RESULTS: There were significant differences in time spent in prone with the Boppy condition affording infants up to three more min in prone across three repeated trials. There were no significant interaction effects between condition and infant size measurements. CONCLUSIONS: These results provide evidence for increasing positional support, such as through use of a Mini Boppy(r), to facilitate tolerance for prone for infants of all sizes. PMID- 27366980 TI - Social Media Use by Transplant Recipients for Support and Healing. AB - Transplant recipients use a diverse support network that now includes transplant related social media support groups. The purpose of this study is to explore the use of social media sites by transplant recipients as a potential source of support and healing and the usefulness of Internet postings as a source of rich qualitative data. A qualitative descriptive design was used for the study. A total of 126 retrospective postings from 58 participants were analyzed as they existed on this open publically available Web site over a 20-month period from the selected discussion threads. Two major themes emerged from the data: sharing overwhelming gratitude and finding sanctuary. Sharing overwhelming gratitude was expressed in emotional postings about feelings and letters to donor families. Finding sanctuary described the recipients' perception of the online community as a safe and nonjudgmental environment to discuss sensitive issues and feelings. This study adds to what is known about the unique psychological and emotional needs of transplant recipients. Transplant-related support Web sites offer the opportunity to learn what matters most to transplant recipients and identify gaps in care related to calls for nursing. PMID- 27366979 TI - Racial/Ethnic Disparities in Genomic Sequencing. AB - IMPORTANCE: Although poorly understood, there is heterogeneity in the molecular biology of cancer across race and ethnicities. The representation of racial minorities in large genomic sequencing efforts is unclear, and could have an impact on health care disparities. OBJECTIVE: To determine the racial distribution among samples sequenced within The Cancer Genome Atlas (TCGA) and the deficit of samples needed to detect moderately common mutational frequencies in racial minorities. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective review of individual patient data from TCGA data portal accessed in July 2015. TCGA comprises samples from a wide array of institutions primarily across the United States. Samples from 10 of the 31 currently available tumor types were analyzed, comprising 5729 samples from the approximately 11 000 available. MAIN OUTCOMES AND MEASURES: Using the estimated median somatic mutational frequency, the samples needed beyond TCGA to detect a 10% and 5% mutational frequency over the background somatic mutation frequency were calculated for each tumor type by racial ethnicity. RESULTS: Of the 5729 samples, 77% (n = 4389) were white, 12% (n = 660) were black, 3% (n = 173) were Asian, 3% (n = 149) were Hispanic, and less than 0.5% combined were from patients of Native Hawaiian, Pacific Islander, Alaskan Native, or American Indian decent. This overrepresents white patients compared with the US population and underrepresents primarily Asian and Hispanic patients. With a somatic mutational frequency of 0.7 (prostate cancer) to 9.9 (lung squamous cell cancer), all tumor types from white patients contained enough samples to detect a 10% mutational frequency. This is in contrast to all other racial ethnicities, for which group-specific mutations with 10% frequency would be detectable only for black patients with breast cancer. Group-specific mutations with 5% frequency would be undetectable in any racial minority, but detectable in white patients for all cancer types except lung (adenocarcinoma and squamous cell carcinoma) and colon cancer. CONCLUSIONS AND RELEVANCE: It is probable, but poorly understood, that ethnic diversity is related to the pathogenesis of cancer, and may have an impact on the generalizability of findings from TCGA to racial minorities. Despite the important benefits that continue to be gained from genomic sequencing, dedicated efforts are needed to avoid widening the already pervasive gap in health care disparities. PMID- 27366981 TI - Structure prediction and functional analyses of a thermostable lipase obtained from Shewanella putrefaciens. AB - Previous experimental studies on thermostable lipase from Shewanella putrefaciens suggested the maximum activity at higher temperatures, but with little information on its conformational profile. In this study, the three-dimensional structure of lipase was predicted and a 60 ns molecular dynamics (MD) simulation was carried out at temperatures ranging from 300 to 400 K to better understand its thermostable nature at the molecular level. MD simulations were performed in order to predict the optimal activity of thermostable lipase. The results suggested strong conformational temperature dependence. The thermostable lipase maintained its bio-active conformation at 350 K during the 60 ns MD simulations. PMID- 27366982 TI - Removal of compounds used as plasticizers and herbicides from water by means of gamma irradiation. AB - Gamma radiation has been used to induce the degradation of compounds used as plasticizers and herbicides such as phthalic acid (PA), bisphenol A (BPA), diphenolic acid (DPA), 2,4-dichlorophenoxy-acetic acid (2,4-D), and 4-chloro-2 methylphenoxyacetic acid (MCPA) in aqueous solution, determining the dose constants, removal percentages, and radiation-chemical yields. The reaction rate constants of hydroxyl radical (HO), hydrated electron (eaq(-)) and hydrogen atom (H) with these pollutants were also obtained by means of competition kinetics, using 3-aminopyridine and atrazine as reference compounds. The results indicated that the elimination of these pollutants with gamma radiation mainly follows the oxidative pathway through reaction with HO radicals. The degradation by-products from the five pollutants were determined, detecting that the hydroxylation of the corresponding parent compounds was the main chemical process in the degradation of the pollutants. Moreover, a high decrease in the chemical oxygen demand has been observed for all pollutants. As expected, the degradation by-products generated by the irradiation of PA, BPA and DPA showed a lower toxicity than the parent compounds, however, in the case of 2,4-D and MCPA irradiation, interestingly, their by-products were more toxic than the corresponding original compounds. PMID- 27366983 TI - Heat waves and urban heat islands in Europe: A review of relevant drivers. AB - The climate change and the proceeding urbanization create future health challenges. Consequently, more people around the globe will be impaired by extreme weather events, such as heat waves. This study investigates the causes for the emergence of surface urban heat islands and its change during heat waves in 70 European cities. A newly created climate class indicator, a set of meaningful landscape metrics, and two population-related parameters were applied to describe the Surface Urban Heat Island Magnitude (SUHIM) - the mean temperature increase within the urban heat island compared to its surrounding, as well as the Heat Magnitude (HM) - the extra heat load added to the average summer SUHIM during heat waves. We evaluated the relevance of varying urban parameters within linear models. The exemplary European-wide heat wave in July 2006 was chosen and compared to the average summer conditions using MODIS land surface temperature with an improved spatial resolution of 250m. The results revealed that the initial size of the urban heat island had significant influence on SUHIM. For the explanation of HM the size of the heat island, the regional climate and the share of central urban green spaces showed to be critical. Interestingly, cities of cooler climates and cities with higher shares of urban green spaces were more affected by additional heat during heat waves. Accordingly, cooler northern European cities seem to be more vulnerable to heat waves, whereas southern European cities appear to be better adapted. Within the ascertained population and climate clusters more detailed explanations were found. Our findings improve the understanding of the urban heat island effect across European cities and its behavior under heat waves. Also, they provide some indications for urban planners on case-specific adaptation strategies to adverse urban heat caused by heat waves. PMID- 27366984 TI - Morpho-physiological response of Populus alba to erythromycin: A timeline of the health status of the plant. AB - Populus alba Villafranca clone was chosen for a proof of concept study to determine the potential uptake and accumulation of antibiotics by trees. Plants were grown hydroponically and irrigated with a recirculating Hoagland's nutrient solution (control) and Hoagland's nutrient solution fortified with erythromycin at 0.01, 0.1 and 1mgL(-1). After 3 and 28days of treatment, poplar plants were separated into roots, stem, and leaves. Plants showed good health all over the period of treatment, and no differences in poplar growth for all the concentrations of erythromycin tested were observed. Quantification of erythromycin was performed using liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS) in positive ion mode using multiple reaction ion monitoring. Erythromycin was detected in all organs analyzed. Roots showed an erythromycin concentration tenfold higher than leaves. The photochemical efficiency of photosystem II did not show a dose-dependant trend. From the quenching analysis of chlorophyll fluorescence, low nonphotochemical quenching (NPQ) and high photochemical quenching (qP) for the first week of erythromycin exposure was observed, depending on leaves position along the stem. Results suggest a short term adaptation of the photosynthetic apparatus of Populus alba in response to environmental realistic erythromycin concentrations. PMID- 27366985 TI - What is unconsciousness in a fly or a worm? A review of general anesthesia in different animal models. AB - All animals are rendered unresponsive by general anesthetics. In humans, this is observed as a succession of endpoints from memory loss to unconsciousness to immobility. Across animals, anesthesia endpoints such as loss of responsiveness or immobility appear to require significantly different drug concentrations. A closer examination in key model organisms such as the mouse, fly, or the worm, uncovers a trend: more complex behaviors, either requiring several sub-behaviors, or multiple neural circuits working together, are more sensitive to volatile general anesthetics. This trend is also evident when measuring neural correlates of general anesthesia. Here, we review this complexity hypothesis in humans and model organisms, and attempt to reconcile these findings with the more recent view that general anesthetics potentiate endogenous sleep pathways in most animals. Finally, we propose a presynaptic mechanism, and thus an explanation for how these drugs might compromise a succession of brain functions of increasing complexity. PMID- 27366986 TI - Epigenetic quality check - how good are your mesenchymal stromal cells? PMID- 27366987 TI - Nonrandomized Intervention Study of Naloxone Coprescription for Primary Care Patients Receiving Long-Term Opioid Therapy for Pain. AB - BACKGROUND: Unintentional overdose involving opioid analgesics is a leading cause of injury-related death in the United States. OBJECTIVE: To evaluate the feasibility and effect of implementing naloxone prescription to patients prescribed opioids for chronic pain. DESIGN: 2-year nonrandomized intervention study. SETTING: 6 safety-net primary care clinics in San Francisco, California. PARTICIPANTS: 1985 adults receiving long-term opioid therapy for pain. INTERVENTION: Providers and clinic staff were trained and supported in naloxone prescribing. MEASUREMENTS: Outcomes were proportion of patients prescribed naloxone, opioid-related emergency department (ED) visits, and prescribed opioid dose based on chart review. RESULTS: 38.2% of 1985 patients receiving long-term opioids were prescribed naloxone. Patients prescribed higher doses of opioids and with an opioid-related ED visit in the past 12 months were independently more likely to be prescribed naloxone. Patients who received a naloxone prescription had 47% fewer opioid-related ED visits per month in the 6 months after receipt of the prescription (incidence rate ratio [IRR], 0.53 [95% CI, 0.34 to 0.83]; P = 0.005) and 63% fewer visits after 1 year (IRR, 0.37 [CI, 0.22 to 0.64]; P < 0.001) compared with patients who did not receive naloxone. There was no net change over time in opioid dose among those who received naloxone and those who did not (IRR, 1.03 [CI, 0.91 to 1.27]; P = 0.61). LIMITATION: Results are observational and may not be generalizable beyond safety-net settings. CONCLUSION: Naloxone can be coprescribed to primary care patients prescribed opioids for pain. When advised to offer naloxone to all patients receiving opioids, providers may prioritize those with established risk factors. Providing naloxone in primary care settings may have ancillary benefits, such as reducing opioid-related adverse events. PRIMARY FUNDING SOURCE: National Institutes of Health. PMID- 27366988 TI - A Comparison of Opioid and Nonopioid Substance Users in Residential Treatment for Co-Occurring Substance Use and Mental Disorders. AB - The past decade has seen a marked increase in the illicit use of opioids, as well as a doubling of the percentage of individuals seeking treatment for opioid use disorders. However, little is known about the differences between opioid users and nonopioid users in residential treatment. Further, no studies have been published that compare opioid users and nonopioid users in treatment for co occurring substance use and mental disorders. To address this gap, this study examined differences between opioid and nonopioid substance users in residential treatment for co-occurring disorders. Data was drawn from 1,972 individuals treated between 2009 and 2011 at one of three private residential treatment centers that provide integrated treatment for co-occurring substance use and mental disorders. Data was collected at program intake, and 1- and 6-month postdischarge using the Addiction Severity Index and the University of Rhode Island Change Assessment. To examine within-group changes in substance use, addiction severity, and mental health across time, linear mixed-model analyses were conducted with facility, year, age, gender, and race included as covariates. The authors found more similarities than differences between the two groups on baseline characteristics, treatment motivation, length of stay, and outcomes on measures of substance use, addiction severity, and mental health. The results demonstrate that though opioid users entered treatment with higher levels of substance use-related impairment, they were just as successful in treatment outcomes as their non-opioid-using peers. PMID- 27366989 TI - Time- and Region-Specific Season of Birth Effects in Multiple Sclerosis in the United Kingdom. AB - IMPORTANCE: The reports of seasonal variation in the births of people who later develop multiple sclerosis (MS) have been challenged and attributed to the background pattern in the general population, resulting in a false association. OBJECTIVE: To study the seasonality of MS births after adjusting for temporal and regional confounding factors. DESIGN, SETTING, AND PARTICIPANTS: A study was conducted using case-control data from 8 MS-specialized centers from the United Kingdom, MS cases from a population-based study in the Lothian and Border regions of Scotland, and death records from the UK Registrar General. Participants included 21 138 patients with MS and control data from the UK Office of National Statistics and the UK government office regions. The seasonality of MS births was evaluated using the Walter and Elwood test, after adjusting for temporal and regional variations in the live births of the UK population. The study was conducted from January 16, 2014, to September 2, 2015. MAIN OUTCOMES AND MEASURES: Diagnosis of multiple sclerosis. RESULTS: Analysis of the general population indicated that seasonal differences are present across time and region in the United Kingdom, with both factors contributing to the monthly distribution of live births. We were able to demonstrate that, when adjusting for the temporal and regional variations in the live births of the UK population, there was a significant season of birth effect in patients with MS, with an increased risk of disease in the peak month (April) compared with the trough month (November) (odds ratio, 1.24; 95% CI, 1.10-1.41) and 15.68% fewer people who developed MS being born in November (observed to expected birth ratio, 0.840; 95% CI, 0.76-0.92). CONCLUSIONS AND RELEVANCE: Season of birth is a risk factor for MS in the United Kingdom and cannot be attributed to the background pattern in the general population. The reasons for the variations in birth rates in the general population are unclear, but not taking them into consideration could lead to false-positive associations. PMID- 27366990 TI - Initial Stop Voicing in Bilingual Children With Cochlear Implants and Their Typically Developing Peers With Normal Hearing. AB - PURPOSE: This study focuses on stop voicing differentiation in bilingual children with normal hearing (NH) and their bilingual peers with hearing loss who use cochlear implants (CIs). METHOD: Twenty-two bilingual children participated in our study (11 with NH, M age = 5;1 [years;months], and 11 with CIs, M hearing age = 5;1). The groups were matched on hearing age and a range of demographic variables. Single-word picture elicitation was used with word-initial singleton stop consonants. Repeated measures analyses of variance with three within-subject factors (language, stop voicing, and stop place of articulation) and one between subjects factor (NH vs. CI user) were conducted with voice onset time and percentage of prevoiced stops as dependent variables. RESULTS: Main effects were statistically significant for language, stop voicing, and stop place of articulation on both voice onset time and prevoicing. There were no significant main effects for NH versus CI groups. Both children with NH and with CIs differentiated stop voicing in their languages and by stop place of articulation. Stop voicing differentiation was commensurate across the groups of children with NH versus CIs. CONCLUSIONS: Stop voicing differentiation is accomplished in a similar fashion by bilingual children with NH and CIs, and both groups differentiate stop voicing in a language-specific fashion. PMID- 27366991 TI - Disclosing Industry Relationships-A Patient-Centered Approach. PMID- 27366993 TI - Unusual Retinal Vascular Proliferation in von Hippel-Lindau Disease. PMID- 27366992 TI - Vesicle-MaNiA: extracellular vesicles in liquid biopsy and cancer. AB - Normal and tumor cells shed vesicles to the environment. Within the large family of extracellular vesicles, exosomes and microvesicles have attracted much attention in the recent years. Their interest ranges from mediators of cancer progression, inflammation, immune regulation and metastatic niche regulation, to non-invasive biomarkers of disease. In this respect, the procedures to purify and analyze extracellular vesicles have quickly evolved and represent a source of variability for data integration in the field. In this review, we provide an updated view of the potential of exosomes and microvesicles as biomarkers and the available technologies for their isolation. PMID- 27366995 TI - Safety of Topical Corticosteroids in Pregnancy. AB - CLINICAL QUESTION: Are topical corticosteroids safe for use in pregnancy? BOTTOM LINE: The available evidence found no associations of maternal use of topical corticosteroids of any potency with mode of delivery, birth defects, preterm delivery, fetal death, and low Apgar score. However, maternal use of potent to very potent topical corticosteroids, especially when the cumulative dosage of topical corticosteroids throughout the pregnancy is very large, is associated with low birth weight. PMID- 27366994 TI - Responses in early visual areas to contour integration are context dependent. AB - It has been shown that early visual areas are involved in contour processing. However, it is not clear how local and global context interact to influence responses in those areas, nor has the interarea coordination that yields coherent structural percepts been fully studied, especially in human observers. In this study, we used functional magnetic resonance imaging (fMRI) to measure activity in early visual cortex while observers performed a contour detection task in which alignment of Gabor elements and background clutter were manipulated. Six regions of interest (two regions, containing either the cortex representing the target or the background clutter, in each of areas V1, V2, and V3) were predefined using separate target versus background functional localizer scans. The first analysis using a general linear model showed that in the presence of background clutter, responses in V1 and V2 target regions of interest were significantly stronger to aligned than unaligned contours, whereas when background clutter was absent, no significant difference was observed. The second analysis using interarea correlations showed that with background clutter, there was an increase in V1-V2 coordination within the target regions when perceiving aligned versus unaligned contours; without clutter, however, correlations between V1 and V2 were similar no matter whether aligned contours were present or not. Both the average response magnitude and the connectivity analysis suggest different mechanisms support contour processing with or without background distractors. Coordination between V1 and V2 may play a major role in coherent structure perception, especially with complex scene organization. PMID- 27366997 TI - Biography - S. W. Benson. PMID- 27366996 TI - Innate immunity against hepatitis C virus. AB - Hepatitis C virus (HCV) infection tends persistent and causes chronic liver diseases, including inflammation, cirrhosis and hepatocellular carcinoma. Innate immune responses triggered by HCV infection, particularly the production of interferons and pro-inflammatory cytokines, shape the early host antiviral defense, and orchestrate subsequent HCV-specific adaptive immunity. Host has evolved multifaceted means to sense HCV infection to induce innate immune responses, whereas HCV has also developed elaborate strategies to evade immune attack. Recent studies in the field have provided many new insights into the interplay of HCV and innate immunity. In this review, we summarized these recent advances, focusing on pathogen recognition by innate sensors, newly discovered anti-HCV innate effectors and new viral strategies to evade innate immunity. PMID- 27366998 TI - Transition-Metal-Free Fluoroarylation of Diazoacetamides: A Complementary Approach to 3-Fluorooxindoles. AB - An efficient transition-metal-free fluoroarylation reaction of N-aryl diazoacetamides with NFSI (N-fluorobenzenesulfonimide) is described. This reaction directly provides 3-fluorooxindole derivatives in yields of 67-93% with high selectivity via a carbene-free process under mild reaction conditions. PMID- 27367000 TI - Bimetallic Nanocrystals: Syntheses, Properties, and Applications. AB - Achieving mastery over the synthesis of metal nanocrystals has emerged as one of the foremost scientific endeavors in recent years. This intense interest stems from the fact that the composition, size, and shape of nanocrystals not only define their overall physicochemical properties but also determine their effectiveness in technologically important applications. Our aim is to present a comprehensive review of recent research activities on bimetallic nanocrystals. We begin with a brief introduction to the architectural diversity of bimetallic nanocrystals, followed by discussion of the various synthetic techniques necessary for controlling the elemental ratio and spatial arrangement. We have selected key examples from the literature that exemplify critical concepts and place a special emphasis on mechanistic understanding. We then discuss the composition-dependent properties of bimetallic nanocrystals in terms of catalysis, optics, and magnetism and conclude the Review by highlighting applications that have been enabled and/or enhanced by precisely controlling the synthesis of bimetallic nanocrystals. PMID- 27366999 TI - Natural Polyphenols in Cancer Chemoresistance. AB - Resistance to chemotherapy remains a major impediment to the management of most types of cancer. Both intrinsic and acquired drug resistance are mediated by several cellular and molecular mechanisms, including alternative growth-signaling pathways unaffected by specific therapies, alterations in the tumor microenvironment (e.g., hypoxia and angiogenesis), and active transport of drugs out of the cell. Epidemiological studies have validated an inverse correlation between the consumption of dietary polyphenols and the risk of cancer, which has been attributed to polyphenol antioxidant capacity and their potential to inhibit activation of procarcinogens, cancer cell proliferation, metastasis, and angiogenesis, and inhibition or downregulation of active drug efflux transporters. Moreover, polyphenols can induce apoptosis in cancer cells and modulate immune responses and inflammatory cascades. Augmentation of the efficacy of chemotherapy and prevention of multidrug resistance are other important effects of dietary polyphenols that deserve further research, especially after the discovery of tight "crosstalk" between aberrant growth signaling and metabolic dysfunction in cancer cells. In this review, we cover what is currently known about the role of natural polyphenolic compounds in overcoming cancer drug resistance mediated by diverse primary and secondary resistance mechanisms. PMID- 27367001 TI - Epidemiological characteristics and antimicrobial susceptibility among carbapenem resistant non-fermenting bacteria in Brazil. AB - INTRODUCTION: Non-fermenting Gram-negative bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii are widespread in the environment and are increasingly associated with nosocomial infections. Extensive and indiscriminate use of antibiotics in hospitals has contributed to an increased number of infections caused by these microorganisms, that are resistant to a wide variety of antimicrobials, including beta-lactams. This study aimed to isolate and identify carbapenem-resistant Acinetobacter spp. and P. aeruginosa from hospitalized patients, to determine their antimicrobial susceptibility patterns and to screen for blaOXA-23, blaOXA-24, blaOXA-51, blaOXA-58, and blaOXA-143 genes among the isolated bacteria. METHODOLOGY: Antimicrobial resistance patterns were performed using the disk-diffusion method. Genetic markers related to carbapenem resistance were screened by polymerase chain reaction. RESULTS: Carbapenem-resistant Acinetobacter spp. (n = 44) and P. aeruginosa (n = 28) samples were isolated from patients admitted to a tertiary hospital. Polymyxin B was the only effective drug for all isolates. Considering the oxacillinase gene screening, genetic markers were observed only in Acinetobacter isolates. The most frequent genotype observed was blaOXA-23+/blaOXA-51+ (45.5%), followed by blaOXA 51+/blaOXA-143+ (41%). The oxacillinase genes blaOXA-24 and blaOXA-58 were not detected. High mortality rates (> 70%) were observed. CONCLUSIONS: The data suggest the need for rational use of antimicrobials associated with early diagnosis of multidrug-resistant bacteria, especially considering non-fermenting Gram-negative rods, which are widespread in hospitals. The findings of blaoxa-51( ) strains suggest the occurrence and spread of non-A. baumannii species throughout our hospitals. Effective implementation of surveillance programs in hospitals is needed to reduce infectious and resistant intra- and inter-species bacteria. PMID- 27367002 TI - Device-associated infections in the pediatric intensive care unit at the American University of Beirut Medical Center. AB - INTRODUCTION: Device-associated healthcare-associated infections (DA-HAIs) are the principal threat to patient safety in intensive care units (ICUs). The primary objective of this study was to identify the most common DA-HAIs in the pediatric intensive care unit (PICU) at the American University of Beirut Medical Center (AUBMC). Length of stay (LOS) and mortality, antimicrobial resistance patterns, and suitability of empiric antibiotic choices for DA-HAIs according to the local resistance patterns were also studied. METHODOLOGY: This was a retrospective study that included all patients admitted to the PICU at AUBMC between January 2007 and December 2011. All patients admitted to the PICU having a placed central line, an endotracheal tube, and/or a Foley catheter were included. Data was extracted from the patients' medical records through chart review. A total of 22 patients were identified with 25 central line-associated bloodstream infections (CLABSI), 25 ventilator-associated pneumonia (VAP), and 9 catheter-associated urinary tract infections (CAUTIs). The causing organisms, their resistance patterns, and the appropriateness of empiric antimicrobial therapy were reported. RESULTS: Gram-negative pathogens were found in 53% of the DA-HAIs, Gram-positive ones in 27%, and fungal organisms in 20%. A total of 80% of K. pneumonia isolates were extended-spectrum beta-lactamases (ESBL) producers, and 30% of Pseudomonas isolates were multidrug resistant. No methicillin resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) were isolated. Based on culture results, the choice of empiric antimicrobial therapy was appropriate in 64% of the DA-HAIs. CONCLUSIONS: After the care bundle approach is adopted in our PICU, DA-HAIs are expected to decrease further. PMID- 27367003 TI - Zika virus infection, associated microcephaly, and low yellow fever vaccination coverage in Brazil: is there any causal link? AB - INTRODUCTION: Since the end of 2014, Zika virus (ZIKV) infection has been rapidly spreading in Brazil. METHODOLOGY: To analyze the possible association of yellow fever vaccine with a protective effect against ZIKV-related microcephaly, the following spatial analyses were performed, using Brazilian municipalities as units: i) yellow fever vaccination coverage in Brazilian municipalities in individuals aged 15-49; ii) reported cases of microcephaly by municipality; and iii) confirmed cases of microcephaly related to ZIKV, by municipality. SaTScan software was used to identify clusters of municipalities for high risk of microcephaly. RESULTS: There were seven significant high risk clusters of confirmed microcephaly cases, with four of them located in the Northeast where yellow fever vaccination rates were the lowest. The clusters harbored only 2.9% of the total population of Brazil, but 15.2% of confirmed cases of microcephaly. CONCLUSION: We hypothesize that pregnant women in regions with high yellow fever vaccination coverage may pose their offspring to lower risk for development of microcephaly. There is an urgent need for systematic studies to confirm the possible link between low yellow fever vaccination coverage, Zika virus infection and microcephaly. PMID- 27367004 TI - Vitamin D level is associated with mortality predictors in ventilator-associated pneumonia caused by Acinetobacter baumannii. AB - INTRODUCTION: Vitamin D plays a role in host defense and is known to be associated with mortality in patients in the intensive care unit (ICU). We aimed to evaluate the relationships between vitamin D levels and predictors of mortality in patients with ventilator-associated pneumonia (VAP) caused by extensively drug-resistant Acinetobacter baumanii (XDR A. baumanii). METHODOLOGY: A retrospective single-center study was conducted in an 18-bed adult ICU of a teaching hospital, including all patients with VAP due to XDR A. baumanii. Levels of 25(OH)D, procalcitonin (PCT), C-reactive protein (CRP), n-terminal pro-BNP (NT proBNP), as well as clinical scores (Sequential Organ Failure Assessment [SOFA], Acute Physiology And Chronic Health Evaluation [APACHE II], Clinical Pulmonary Infection Score [CPIS) were recorded. RESULTS: Forty-for patients were studied over six months. All patients had vitamin D deficiency. The 28-day mortality in patients with 25(OH)D levels <= 10 ng/mL was higher than in patients with 25(OH)D > 10ng/mL (p = 0.001). The fourth- and seventh-day SOFA scores (p= 0.04 and p= 0.001) and first- and fourth-day procalcitonin levels (p = 0.03 and p = 0.004) were higher in patients with 25(OH)D levels <= 10 ng/mL. The clinical scores (SOFA, CPIS, and CEPPIS) and biomarkers (NT-proBNP, PCT) were negatively correlated with 25(OH)D levels in all study groups. CONCLUSIONS: Severe vitamin D deficiency was associated with adverse outcome in VAP due to XDR A. baumanii. Vitamin D levels may be a prognostic predictor of VAP. It is also important to evaluate the effect of rapid vitamin D replacement on mortality. PMID- 27367005 TI - Distribution of ESBLs among Escherichia coli isolates from outpatients with recurrent UTIs and their antimicrobial resistance. AB - INTRODUCTION: Extended-spectrum beta-lactamase (ESBL)-producing strains of Enterobacteriaceae are considered to be emerging pathogens. They are a major problem in hospitalized as well as community-based patients. Major outbreaks involving ESBL strains have been reported from all over the world. Recurrent urinary tract infection (UTI) is one of the risk factors for infection with ESBL producing E. coli in hospitalized and non-hospitalized patients. METHODOLOGY: Ninety-one E. coli isolates from outpatients with recurrent UTIs were surveyed phenotypically and genotypically for ESBL production and tested for antimicrobial susceptibility. RESULTS: Of 91 E. coli isolates, 75.8% were resistant to each of cefotaxime and ceftazidime and 74.7% produced ESBLs. CTX-M-type was the most frequent ESBL (accounting for 70.3%), with CTX-M-1 being the only subtype possessed by these isolates. The prevalence of OXA- and SHV-type was 32.9% and 10.9%, respectively. None of the isolates produced TEM beta-lactamase. All OXA type ESBL were produced concomitantly with CTX-M1. Both ESBL producers and non producers had high resistance to ampicillin followed by trimethoprim sulphamethoxazole, third-generation cephalosporins, and tetracycline. No isolate showed resistance to imipenem and meropenem. In total, resistance rates of ESBL producers were higher than those of ESBL non-producers, as was multidrug resistance (52.7% versus 8.7%, respectively). CONCLUSIONS: Our study documented high distribution of ESBLs among E. coli isolates from outpatients with recurrent UTIs, with CTX-M as the predominant ESBL. In the current situation, it is important that antibiotic treatment is be started only after a proper sensitivity report is obtained from the laboratory. PMID- 27367006 TI - Detection of phenotypes, virulence genes and phylotypes of avian pathogenic and human diarrheagenic Escherichia coli in Egypt. AB - INTRODUCTION: The purpose from this study was to determine phenotypes, intestinal virulence-associated genes, and phylotypic profiling of human diarrheagenic E. coli (DEC) and avian pathogenic E. coli (APEC). METHODOLOGY: A total of 108 chicken visceral organs (liver, spleen, heart) from 36 diseased birds (three organs per each bird) and 78 human stool samples (50 diarrheic patients and 28 healthy persons) were randomly collected during the first half of 2015 in the district of Mansoura city, Egypt. Conventional culturing, serotyping, and molecular characterization of virulence genes and phylogroups were performed. RESULTS: Sixty-five (35%) biochemically identified E. coli isolates were detected from chicken visceral (29/108; 26.9%) and human stool samples (36/78; 46.2%). Serotypes O78, O2, and O1 were the most prevalent serotypes (62%) distinguished from APEC isolates, and only two similar serotypes (O119:H4 and O26:H11) were identified from both APEC and DEC isolates. By polymerase chain reaction (PCR), the respective percentages of 100 and 35 with eae and Shiga toxin genes were detected from APEC isolates while 50%, 27.8%, and 19.4% of human DEC isolates harbored eae, stx1, and stx2 genes, respectively. Phylogrouping revealed a significantly higher occurrence of pathogenic phylogroups (D and B2) in APEC (19/29; 65.5%) than in human DEC isolates (8/36; 22.2%). CONCLUSIONS: APEC isolates shared serotypes, virulence genes, and phylotypes with human DEC isolates, which is a subsequent potential public health concern. To the best of our knowledge, this is the first report in Egypt that determines virulence gene and phylogroup coexistence between APEC and DEC isolates. PMID- 27367007 TI - Physiological and molecular characteristics of carbapenem resistance in Klebsiella pneumoniae and Enterobacter aerogenes. AB - INTRODUCTION: Bacterial resistance is a growing concern in the nosocomial environment in which Klebsiella pneumoniae and Enterobacter aerogenes play an important role due to their opportunism and carbapenemase-production. This work aimed to evaluate physiological and molecular characteristics of carbapenem resistant K. pneumoniae and E. aerogenes isolated in a Brazilian tertiary hospital. METHODOLOGY: In total, 42 carbapenem-resistant bacteria isolated from clinical specimens were included (21 K. pneumoniae and 21 E. aerogenes). Drug sensitive K. pneumoniae (n = 27) were also included. Antimicrobial susceptibility and biocide tolerance patterns, hemolytic activity, tolerance to oxidative stress, and aggregative ability were assessed. Genetic markers related to carbapenem resistance, or ESBL-production were screened by PCR. RESULTS: Compared to drug-sensitive strains, carbapenem-resistant K. pneumoniae were more tolerant to biocides and to oxidative stress, and they displayed an increase in biofilm formation. The genetic markers blaKPC (95.2%) and blaTEM (90.5%) were the most frequent. Among the carbapenem-resistant E. aerogenes strains, blaKPC, and blaTEM were detected in all bacteria. Drug-sensitive E. aerogenes were not isolated in the same period. blaSHV, blaVIM, and blaCTX markers were also observed among carbapenem-resistant bacteria. CONCLUSIONS: Results suggest that carbapenemase producing enterobacteria might show peculiar characteristics regarding their physiology associated with their environmental persistency, virulence, and multidrug resistance. The observed phenomenon may have implications not only for antimicrobial chemotherapy, but also for the prognosis of infectious diseases and infection control. PMID- 27367008 TI - Role of efflux pump inhibitor in decreasing antibiotic cross-resistance of Pseudomonas aeruginosa in a burn hospital in Iran. AB - INTRODUCTION: Multidrug resistance in Pseudomonas aeruginosa may be due to efflux pump overexpression. This study phenotypically examined the role of efflux pump inhibitors in decreasing antibiotic cross-resistance between beta-lactams, fluoroquinolones, and aminoglycosides in P. aeruginosa isolates from burn patients in Iran. METHODOLOGY: A total of 91 phenotypically and genotypically confirmed P. aeruginosa samples were studied. Multidrug cross-resistance was determined using the disk diffusion method and minimum inhibitory concentration (MIC) test. The contribution of efflux pumps was determined by investigating MIC reduction assay to markers of beta-lactams, fluoroquinolones, and aminoglycosides in the absence and presence of an efflux pump inhibitor. All the isolates were also tested by polymerase chain reaction for the presence of mexA, mexC, and mexE efflux genes. RESULTS: Of the isolates, 81 (89%) and 83 (91.2%) were multidrug resistant according to the disk diffusion and MIC method, respectively. Cross resistance was observed in 67 (73.6%) and 68 (74.7%) of isolates according to the disk diffusion and MIC method, respectively. In the presence of the efflux pump inhibitor, twofold or higher MIC reduction to imipenem, cefepime, ciprofloxacin, and gentamicin was observed in 59, 65, 55, and 60 isolates, respectively. Except for two isolates that were negative for mexC, all isolates were positive for mexA, mexC, and mexE genes simultaneously. CONCLUSION: Efflux pumps could cause different levels of resistance based on their expression in clinical isolates. Early detection of different efflux pumps in P. aeruginosa could allow the use of other antibiotics and efflux pump inhibitors in combination with antibiotic therapy. PMID- 27367009 TI - Effectiveness of etravirine-based therapy for treatment-experienced HIV-infected patients. AB - INTRODUCTION: Treatment options are limited for HIV-1-infected individuals who have received extensive previous antiretroviral therapy. ETV has shown significant clinical benefits in treatment-experienced HIV-1+ patients with antiretroviral resistance. The aim of this study was to evaluate the effectiveness of ETV plus optimized background regimen in real-life conditions in a cohort of highly HIV-1 antiretroviral-experienced patients. METHODOLOGY: Retrospective cohort of treatment-experienced HIV-1-infected adults with virological failure who started therapy with an ETV-containing regimen. The effectiveness was evaluated using HIV-1 RNA viral load and changes in CD4+ cell count after 48 weeks of treatment. RESULTS: Forty-two patients >= 16 years of age were included; 74% were men, and the median age was 45 years (IQR 41-53). All participants had prior non-nucleoside reverse transcriptase inhibitor use (55% nevirapine, 83%, efavirenz, and 28% both). Baseline median HIV-1 RNA viral load was 15,598 copies/mL (IQR 2651-84,175) and CD4+ cell count was 276 cells/mL (IQR 155-436). After 48 weeks of treatment, 90.5% (95% CI 78-96) of patients had HIV-1 RNA viral load < 200 copies/mL and 76% (95% CI 61-86) had < 50 copies/mL. CD4+ cell counts increased from baseline to 48 weeks of treatment to a median of 407 cells/mL (IQR 242-579); p < 0.001. Virological outcome was associated with virological failure at baseline HIV-1 RNA viral load >= 100,000 copies/mL (OR 7.6; 95% CI 1.2-44.80; p = 0.025). CONCLUSIONS: Our study provides clinically important evidence of the effectiveness and safety of ETV in highly antiretroviral-experienced HIV-1-infected patients. PMID- 27367010 TI - Epidemiological characteristics and pathogens attributable to hand, foot, and mouth disease in Shanghai, 2008-2013. AB - INTRODUCTION: Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by enteroviruses. A passive surveillance system has been implemented in Shanghai Pudong since 2008 and etiology surveillance since 2009.We characterized the epidemiology and the etiology of HFMD in Pudong from 2008-2013. METHODOLOGY: Health care providers were required to report any clinically diagnosed HFMD to Pudong District Center for Disease Control and Prevention. For all severe cases and randomly selected mild HFMD cases, throat or rectal swabs or feces were collected for enterovirus detection by real time reverse transcription polymerase chain reaction. RESULTS: A total of 50,149 cases were reported, with average 8,508 per year (range: 3,577-13,202) and average incidence of 167.5/100,000 persons (range: 81.4-254.1/100,000 persons). HFMD was more likely to occur in children under five years of age (85.6%), while severe cases were more likely to happen in children under three years of age (63.9%). Every year in May or June, HFMD peaked in the region; two peaks were observed from 2011 to 2013.The most common etiologic agents are EV71 and CA16.Different types of enterovirus circulate in different years. EV71 was the predominant pathogen in severe cases. The proportions of EV71 in severe cases was higher than in mild cases at the children's medical center (p<0.001). CONCLUSIONS: HFMD remains an important public health issue in Shanghai. HFMD pathogen surveillance is required for more types of enteroviruses besides EV71 and CA16, which would give a better picture of the etiology of HFMD. PMID- 27367011 TI - Prevalence of serological markers and nucleic acid for blood-borne viral infections in blood donors in Al-Baha, Saudi Arabia. AB - INTRODUCTION: Data on blood-borne viral infections in some regions in Saudi Arabia remain scarce. This study investigates the prevalence of serological markers and nucleic acid for blood-borne viruses among blood donors in Al-Baha, Kingdom of Saudi Arabia. METHODOLOGY: In this cross-sectional study, 2,807 donors who donated blood between January 2009 and November 2011 were investigated for blood-borne viral serological markers including HBsAg, anti-HBc, anti-HBs, anti HCV, anti-HIV, and anti-HTLVI/III in addition to viral nucleic acid. RESULTS: All donors were males between 16 to 66 years of age (mean: 31.5 +/- 9.3 years). Viral nucleic acid and/or serological markers were detected in a total of 36 (1.3%) donors; of them, 26 (72.2%) had nucleic acid concomitant with serological markers, 6 (16.7%) had only viral nucleic acid, while 4 (11.1%) had only serological markers. Of all donors, 22 (0.8%) had HBsAg, 227 (8.0%) had anti-HBc, 157 (5.0%) had anti-HBs, 2,577 (91.8%) had no HBV markers, 2 (0.07%) had anti HIV, 1 (0.04%) had anti-HCV, and 1 (0.04%) had anti-HTLVI/II. The donors who were born during HBV vaccination era showed no HBsAg (0.0%; p = 0.052), lower rates of anti-HBc (1.5%; p < 0.001) and anti-HBs (0.7%; p < 0.001), while the majority had no HBV markers (98.5%; p < 0.001). CONCLUSIONS: Combined viral nucleic acid and serological testing of donated blood enhances blood safety. The absence of HBV markers among donors suggests susceptibility or declined anti-HBs levels. Thus, HBV revaccination or a vaccine boost among adolescents and adults might be indispensable. PMID- 27367012 TI - Inhibition of Ebola Virus by Anti-Ebola miRNAs in silico. AB - INTRODUCTION: MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate transcriptional and posttranscriptional gene regulation of the organisms. miRNA provides immune defense when the body is faced with challenges intracellular agents. miRNA molecules trigger gene silencing in eukaryotic cells. More than 3,000 different human miRNAs (hsa-miRs) have been identified thus far. During ontogenesis, viral or intracellular parasitic infections, miRNAs are differentially expressed to protect the host from intracellular invaders. In a viral infection context, miRNAs have been connected with the interplay between host and pathogen, and occupy a major role in pathogenesis. METHODOLOGY: An in silico approach was used to analyze the four major Ebola Virus genome sequences including the recently characterized Ebola virus responsible for West African epidemic that has killed over 10,000 people. All totaled, 2,543 mature human miRNA sequences were retrieved through an miR-database, and the identification of mature miRNAs were aligned with full length sequences of the four major Ebola viruses via computational tools. RESULTS: We identified 32 miRNAs that exhibited significant inhibitory capacity to block more than one EBV strains. miR-607 showed capacity to quell all four major EBVs. Ten putative miRNAs were found to have near perfect identity at seed sequences with numerous targets of Ebola virus that may completely degrade the viral transcripts. CONCLUSION: We hypothesize that a miRNA-based vaccine can quell Ebola virus infection. Future approaches will focus on validation of these miRNAs in quelling the Ebola virus to further elucidate their biological functions in primate and other animal models. PMID- 27367013 TI - Methylene blue inhibits lumefantrine-resistant Plasmodium berghei. AB - INTRODUCTION: Chemotherapy still is the most effective way to control malaria, a major public health problem in sub-Saharan Africa. The large-scale use of the combination therapy artemether-lumefantrine for malaria treatment in Africa predisposes lumefantrine to emergence of resistance. There is need to identify drugs that can be used as substitutes to lumefantrine for use in combination therapy. Methylene blue, a synthetic anti-methemoglobinemia drug, has been shown to contain antimalarial properties, making it a candidate for drug repurposing. The present study sought to determine antiplasmodial effects of methylene blue against lumefantrine- and pyrimethamine-resistant strains of P. berghei. METHODOLOGY: Activity of methylene blue was assessed using the classical four-day test on mice infected with lumefantrine-resistant and pyrimethamine-resistant P. berghei. A dose of 45 mg/kg/day was effective for testing ED90. Parasitemia and mice survival was determined. RESULTS: At 45 mg/kg/day, methylene blue sustained significant parasite inhibition, over 99%, for at least 6 days post-treatment against lumefantrine-resistant and pyrimethamine-resistant P. berghei (p = 0.0086 and p = 0.0191, respectively). No serious adverse effects were observed. CONCLUSIONS: Our results indicate that methylene blue at a concentration of 45 mg/kg/day confers over 99% inhibition against lumefantrine- and pyrimethamine resistant P. berghei for six days. This shows the potential use methylene blue in the development of antimalarials against lumefantrine- and pyrimethamine resistant parasites. PMID- 27367014 TI - Surveillance and characterization of Candida bloodstream infections in a Serbian tertiary care hospital. AB - INTRODUCTION: Candida spp. frequently cause hospital-acquired bloodstream infections (BSI) with a high mortality rate (up to 70%). We analyzed the frequency, infection characteristics, potential predisposing factors, susceptibility to antifungal drugs, biofilm production and other virulence characteristics of Candida spp. isolates obtained from a tertiary care hospital in Nis, Serbia, during a one year period. METHODS: Medical histories, characteristics of isolated strains and drug susceptibility, as well as the effect on the function of isolated macrophages and other virulence features were evaluated. The obtained results were subjected to student's t-test and multivariate statistical analyzes. RESULTS: Herein we report an annual incidence of 3.65 cases of C. albicans, C. lusitaniae and C. lipolytica infections per 105 population. Out of eight isolated strains, two (25%) were shown to be strong biofilm producers, one (12.5%) caused hemolysis on blood agar and in two (25%) cases macrophages were able to completely eliminate the yeast colonies. Chronic kidney disease, diabetes, malignant and other diseases were present in 37.5, 62.5, 50 and 75%, respectively, in the study group. All patients with Candida BSI received antifungal therapy (amphotericin B), however, hospital mortality was observed in 25% of patients. CONCLUSIONS: Evaluation of local Candida epidemiology, antifungal susceptibility and virulence factors, as well as personalized patient risk factors are important for the surveillance of Candida BSI, especially in intensive care unit patients and may contribute to the improved options and outcome for patients with Candida BSI. PMID- 27367015 TI - Five-year analysis of rickettsial fevers in children in South India: Clinical manifestations and complications. AB - INTRODUCTION: Rickettsial infections are re-emerging in the Indian subcontinent, especially among children. Understanding geographical and clinical epidemiology will facilitate early diagnosis and management. METHODOLOGY: Children aged <18yrs hospitalized with clinically-diagnosed rickettsial fever were reviewed retrospectively. Frequency distributions and odds ratios were calculated from tabulated data. RESULTS: Among 262 children hospitalized between January 2008 December 2012, median age was five years, and 61% were male children. Hospitalized cases increased steadily every year, with the highest burden (74%) occurring between September and January each year. Mean duration of fever was 11.5 days. Rash was present in 54.2% (142/262) of children, with 37.0% involving palms and soles. Prevalence of malnutrition was high (45% of children were underweight and 28% had stunting). Retinal vasculitis was seen in 13.7% (36/262), and the risk appeared higher in females. Severe complications were seen in 29% (purpura fulminans, 7.6%; meningitis and meningoencephalitis, 28%; septic shock, 1.9%; acute respiratory distress syndrome, 1.1%). Complications were more likely to occur in anemic children. Positive Weil-Felix test results (titers >=1:160) were seen in 70% of cases. Elevated OX-K titers suggestive of scrub typhus were seen in 80% (147/184). Patients were treated with chloramphenicol (32%) or doxycycline (68%). Overall mortality among hospitalised children was 1.9%. CONCLUSIONS: This five-year analysis from southern India shows a high burden and increasing trend of rickettsial infections among children. The occurrence of retinal vasculitis and a high rate of severe complications draw attention to the need for early diagnosis and management of these infections. PMID- 27367016 TI - Clonal persistence of Salmonella enterica serovars Montevideo, Tennessee, and Infantis in feed factories. AB - INTRODUCTION: Novel molecular techniques applied in biotechnology research have provided sound evidence on clonal persistence of distinct serovars of Salmonella in feed factory environments, over long periods of time (months, even years), which can be responsible for repeated in-house contamination of final products. In this study, we examined the possibility of clonal persistence of isolates of three Salmonella serovars that have been repeatedly identified in animal feed samples from three feed factories throughout a two-year period. METHODOLOGY: The isolates Salmonella enterica serovars Tennessee (n = 7), Montevideo (n = 8), and Infantis (n = 4) were tested for genetic diversity using pulsed-field gel electrophoresis (PFGE) and multicellular behavior patterns by applying the Congo red agar test. RESULTS: SpeI and XbaI macro-restriction profiles indicated that isolates S. Montevideo and S. Infantis were identical, whereas isolates of S. Tennessee demonstrated greater genetic diversity, although the genetic differences did not exceed 10%. All Salmonella serovars demonstrated the ability to produce predominant matrix compounds essential for biofilm formation, curli fimbriae and cellulose. CONCLUSIONS: The identification of identical clones of S. Montevideo and S. Infantis, as well as the minor genetic diversity of S. Tennessee, which have been repeatedly isolated from animal feed in three production plants throughout a two-year period, indirectly suggests the possibility of their persistence in feed factory environments. Their ability to express the key biofilm matrix components further supports this hypothesis. PMID- 27367017 TI - Toxoplasma gondii infection among pregnant women in Yemen: Factors associated with high seroprevalence. AB - INTRODUCTION: Although toxoplasmosis is an important public health problem, there is scarcity of data on the disease available from Yemen. A cross-sectional survey was conducted in health facilities to determine seroprevalence of Toxoplasma gondii and associated risk factors among pregnant women in Sana'a, the capital city of Yemen. METHODOLOGY: A total of 593 pregnant women were included and examined for anti-T. gondii antibodies (Ab) using enzyme-linked immunosorbent assay. Bio and socio-demographic data were collected by pre-tested structured questionnaires through face-to-face interviews. RESULTS: The overall seroprevalence of T. gondii was 45.4% (95% confidence interval: 41%-49%). The prevalence of anti-T. gondii IgG and IgM was 43.7 (95% CI: 40-%48%) and 9.1% (95% CI: 7%-12%), respectively. About 7.4 (95% CI: 6%-10%) of pregnant women were seropositive for both IgG and IgM Abs. Multivariate logistic regression analysis identified the following risk factors for toxplasmosis (IgG and/or IgM): age >= 25 years (adjusted OR: 2.02, 95% CI: 1.44-2.84, p < 0.001), rearing cats in the house (OR: 1.75, 95% CI: 1.20-2.55, p = 0.004), and contact with soil (OR: 1.90, 95% CI: 1.32-2.75, p = 0.001). CONCLUSIONS: The study reported high seroprevalence among pregnant women in Sana'a, Yemen, with a high proportion of pregnant women having a possibility of acute toxoplasmosis. This highlights the need for including routine screening for T. gondii in pregnant women in the country's antenatal clinics. In addition, health education on the mode of transmission of toxoplasmosis should be provided for pregnant women in Yemen. PMID- 27367018 TI - First molecular evidence of intrauterine and surgical-site infections caused by Streptococcus dysgalactiae subsp. equisimilis. AB - S. dysgalactiae subsp. equisimilis (SDSE) is infrequently associated with maternal infections during delivery in pregnant women. A rare case is presented of a woman with intrauterine infection and surgical-site infection due to SDSE after cesarean section, which had colonized her genital tract and, via the ascending pathway, reached her intact fetal membrane. All isolates were identified as Streptococcus Lancefield group G, and their emm genes that coded M protein belonged to stG6.1. The isolates tested negative for a series of streptococcal superantigen virulence genes but positive for nonsuperantigenic virulence genes. In particular, molecular typing using pulsed-field gel electrophoresis analysis disclosed that the three isolates from the different infection sites had identical profiles. Furthermore, multilocus sequence typing indicated that the three isolates belonged to a new sequence typing. Our results indicated that SDSE is potentially pathogenic for pregnant women and newborns if colonized. PMID- 27367019 TI - Application of protein profiling of virulent Haemophilus parasuis by MALDI-TOF mass spectrometry. PMID- 27367020 TI - An additional observation of Plasmodium vivax malaria infection in Duffy-negative individuals from Cameroon. PMID- 27367021 TI - A Common Cause of Cranial Nerve VI Palsy-Hidden in Plain Sight: A Teachable Moment. PMID- 27367022 TI - Team Physician Symposium. PMID- 27367023 TI - Extracellular translationally controlled tumor protein promotes colorectal cancer invasion and metastasis through Cdc42/JNK/ MMP9 signaling. AB - The translationally controlled tumor protein (TCTP) can be secreted independently of the endoplasmic reticulum/Golgi pathway and has extrinsic activities when it is characterized as the histamine releasing factor (HRF). Despite its important role in allergies and inflammation, little is known about how extracellular TCTP affects cancer progression. In this study, we found that TCTP was overexpressed in the interstitial tissue of colorectal cancer (CRC) and its expression correlated with poor survival, high pathological grades and metastatic TNM stage in CRC patients. TCTP expression was greater in metastatic liver tissue than in primary tumors and was increased in highly invasive CRC cells. We demonstrated that the expression of TCTP was regulated by HIF-1alpha and its release was increased in response to low serum and hypoxic stress. Recombinant human TCTP (rhTCTP) promoted the migration and invasiveness of CRC cells in vitro and contributed to distant liver metastasis in vivo. Furthermore, rhTCTP activated Cdc42, phosphorylated JNK (p-JNK), increasing the translocation of p-JNK from the cytoplasm to the nucleus, as well as the secretion of MMP9. In addition, the expression of TCTP positively correlated with that of Cdc42 and p-JNK in clinical CRC samples. The silencing of Cdc42, JNK and MMP9 significantly inhibited the Matrigel invasion of rhTCTP-enhanced CRC cells. Collectively, these results identify a new role for extracellular TCTP as a promoter of CRC progression and liver metastases via Cdc42/JNK/MMP9 activation. PMID- 27367024 TI - ASC contributes to metastasis of oral cavity squamous cell carcinoma. AB - ASC (Apoptosis-associated Speck-like protein containing a CARD) acts as a platform protein in the inflammasome cascade of some cancer types. However, its potential involvement in OSCC (oral cavity squamous cell carcinoma) has not yet been determined. Here, we investigated the potential role of ASC in OSCC. RT-qPCR analysis of 20 paired tumor and adjacent normal tissue samples revealed that the mRNA levels of ASC, along with IL-1beta, CASP1, and NLRP3 in ASC-associated NLRP3 inflammasome were significantly elevated in OSCC tissues. Immunohistochemical staining of these four proteins in 111 clinical specimens revealed that high level expression of ASC was significantly associated with tumor stage, node stage (p=0.001), overall stage (p<0.001), extracapsular spread (p<0.001), perineural invasion (p=0.004) and tumor depth (p<0.001). Kaplan-Meier survival analysis further revealed that high-level ASC expression was correlated with poorer overall survival (p=0.001), disease-specific survival (p<0.001) and disease-free survival (p<0.001). Studies using OSCC cell lines indicated that high-level ASC expression enhanced cell migration and invasion, and experiments using an orthotropic nude mouse model confirmed that ASC overexpression induced metastasis of OSCC cells. This is the first report to show that ASC contributes to OSCC metastasis, and that high-level ASC expression is a marker for poor prognosis in OSCC patients. PMID- 27367025 TI - Class A1 scavenger receptor modulates glioma progression by regulating M2-like tumor-associated macrophage polarization. AB - Macrophages enhance glioma development and progression by shaping the tumor microenvironment. Class A1 scavenger receptor (SR-A1), a pattern recognition receptor primarily expressed in macrophages, is up-regulated in many human solid tumors. We found that SR-A1 expression in 136 human gliomas was positively correlated with tumor grade (P<0.01), but not prognosis or tumor recurrence. SR A1-expressing macrophages originated primarily from circulating monocytes attracted to tumor tissue, and were almost twice as numerous as resident microglia in glioma tissues (P<0.001). The effects of SR-A1 on glioma proliferation and invasion were assessed in vivo using an SR-A1-deficient murine orthotopic glioma model. SR-A1 deletion promoted M2-like tumor-associated macrophage (TAM) polarization in mice by activating STAT3 and STAT6, which resulted in robust orthotopic glioma proliferation and angiogenesis. Finally, we found that HSP70 might be an endogenous ligand that activates SR-A1-dependent anti-tumorigenic pathways in gliomas, although its expression does not appear informative for diagnostic purposes. Our findings demonstrate a relationship between TAMs, SR-A1 expression and glioma growth and provide new insights into the pathogenic role of TAMs in glioma. PMID- 27367026 TI - Sirtuin 3 enhanced drug sensitivity of human hepatoma cells through glutathione S transferase pi 1/JNK signaling pathway. AB - SIRT3, a class III histone deacetylase, has been implicated in various cancers as a novel therapeutic target. In hepatocellular carcinoma (HCC), we previously reported that SIRT3 induced cell apoptosis by regulating GSK-3beta/Bax signaling pathway. Downregulation of SIRT3 in HCC cells facilitates tumor cell survival. In this study, we found that chemotherapeutic agents (doxorubicin, cisplatin and epirubicin) and sorafenib treatment downregulated SIRT3 mRNA and protein levels in three HCC cell lines. MTS assay found that SIRT3 overexpression sensitized liver cancer cells to chemotherapeutic agents and sorafenib in SMMC-7721, Huh-7 and PLC/PRF/5 cell lines. Moreover, SIRT3 overexpression promoted chemotherapeutic agents-induced or sorafenib-induced apoptosis as evidenced by flow cytometry, enhanced PARP cleavage and enhanced Caspase-9 cleavage in three HCC cells. In contrast, SIRT3 silencing increased drug resistance of HCC cells to chemotherapeutic agents. Mechanistic study found that SIRT3 downregulated the mRNA and protein levels of glutathione S-transferase pi 1 (GSTP1), which is a member of phase II detoxification enzymes families involved in metabolizing for chemotherapeutic agents. Moreover, SIRT3 decreased the amount of GSTP1 that was associated with JNK, which finally contributed the activation of JNK activity and activation of downstream target c-Jun and Bim. Importantly, GSTP1 overexpression or JNK inhibitor abolished SIRT3-induced apoptosis in HCC cells exposed to chemotherapeutic agents. Finally, there was a negative correlation between SIRT3 expression and GSTP1 expression in human HCC tissues. Together, our findings revealed SIRT3 could enhance the drug sensitivity of HCC cells to an array of chemotherapeutic agents. SIRT3 may serve as a potential target for improving the chemosensitivity of HCC patients. PMID- 27367027 TI - Inflammatory related gene IKKalpha, IKKbeta, IKKgamma cooperates to determine liver cancer stem cells progression by altering telomere via heterochromatin protein 1-HOTAIR axis. AB - Cancer stem cells are associated with tumor recurrence. IKK is a protein kinase that is composed of IKKalpha, IKKbeta, IKKgamma. Herein, we demonstrate that IKKalpha plus IKKbeta promoted and IKKgamma inhibited liver cancer stem cell growth in vitro and in vivo. Mechanistically, IKKalpha plus IKKbeta enhanced and IKKgamma inhibited the interplay among HP1alpha, HP1beta and HP1gamma that competes for the interaction among HP1alpha, SUZ12, HEZ2. Therefore, IKKalpha plus IKKbeta inhibited and IKKgamma enhanced the activity of H3K27 methyltransferase SUZ12 and EZH2, which methylates H3K27 immediately sites on HOTAIR promoter region. Therefore, IKKalpha plus IKKbeta increased and IKKgamma decreased the HOTAIR expression. Strikingly, IKKalpha plus IKKbeta decreases and IKKgamma increases the HP1alpha interplays with DNA methyltransferase DNMT3b, which increases or decreases TERRA promoter DNA methylation. Thus IKKalpha plus IKKbeta reduces and IKKgamma increases to recruit TRF1 and RNA polymerase II deposition and elongation on the TERRA promoter locus, which increases or decreases TERRA expression. Furthermore, IKKalpha plus IKKbeta decreases/increases and IKKgamma increases/decreases the interplay between TERT and TRRRA/between TERT and TREC. Ultimately, IKKalpha plus IKKbeta increases and IKKgamma decreases the telomerase activity. On the other hand, at the telomere locus, IKKalpha plus IKKbeta increases/drcreases and IKKgamma decreases/increases TRF2, POT1, pPOT1, Exo1, pExo1, SNM1B, pSNM1B/CST-AAF binding, which keep active telomere regulatory genes and poised for telomere length. Strikingly, HOTAIR is required for IKKalpha plus IKKbeta and IKKgamma to control telomerase activity and telomere length. These observations suggest that HOTAIR operates the action of IKKalpha, IKKbeta, IKKgamma in liver cancer stem cells. This study provides a novel basis to elucidate the oncogenic action of IKKalpha, IKKbeta, IKKgamma and prompts that IKKalpha, IKKbeta, IKKgamma cooperate to HOTAR to be used as a novel therapeutic targets for liver cancer. PMID- 27367028 TI - Evaluation of the risk of lymphomagenesis in xenografts by the PCR-based detection of EBV BamHI W region in patient cancer specimens. AB - Establishment of patient-derived tumor xenografts (PDXs) is hampered by lymphomagenesis mostly caused by the latently-infected Epstein-Barr virus (EBV) contained in patient cancer tissues. However, the character of patient tissues that result in lymphomagenesis after xenotransplantation is not elucidated. In this study, we analyzed the patient colorectal cancer (CRC) tissues and the PDXs established by their xenotransplantation. We found that 2 of 9 (22%) PDX tumors were EBV-associated human diffuse large B cell lymphoma which was formed by clonal proliferation of human B-cell lymphocytes, were strongly positive for EBER ISH, and were classified as type III latency. Expression of EBV genes and RNAs, such as EBNAs, LMP1, EBER and EBV-associated microRNAs in patient CRC tissues were unlikely to be associated with lymphomagenesis in PDXs. In contrast, the positive PCR-based amplification of BamHI W region, a major internal repeat in EBV genome, in the patient CRC tissues was correlated with lymphomagenesis in PDXs. These results suggest that the detection of the EBV BamHI W region in the patient surgical specimens will be an effective way to predict the risk of lymphomagenesis in PDXs before xenotransplantation. PMID- 27367029 TI - Inducible nitric oxide synthase enhances disease aggressiveness in pancreatic cancer. AB - Pancreatic cancer is one of the most lethal malignancies and is refractory to the available treatments. Pancreatic ductal adenocarcinoma (PDAC) expresses high level of inducible nitric oxide synthase (NOS2), which causes sustained production of nitric oxide (NO). We tested the hypothesis that an aberrantly increased NO-release enhances the development and progression of PDAC. Enhanced NOS2 expression in tumors significantly associated with poor survival in PDAC patients (N = 107) with validation in independent cohorts. We then genetically targeted NOS2 in an autochthonous mouse model of PDAC to examine the effect of NOS2-deficiency on disease progression and survival. Genetic ablation of NOS2 significantly prolonged survival and reduced tumor severity in LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre (KPC) mice. Primary tumor cells isolated from NOS2 deficient KPC (NKPC) mice showed decreased proliferation and invasiveness as compared to those from KPC mice. Furthermore, NKPC tumors showed reduced expression of pERK, a diminished inactivation of Forkhead box transcription factor O (FOXO3), a tumor suppressor, and a decrease in the expression of oncomir 21, when compared with tumors in KPC mice. Taken together, these findings showed that NOS2 is a predictor of prognosis in early stage, resected PDAC patients, and provide proof-of-principle that targeting NOS2 may have potential therapeutic value in this lethal malignancy. PMID- 27367030 TI - Acquired nintedanib resistance in FGFR1-driven small cell lung cancer: role of endothelin-A receptor-activated ABCB1 expression. AB - Genomically amplified fibroblast growth factor receptor 1 (FGFR1) is an oncogenic driver in defined lung cancer subgroups and predicts sensibility against FGFR1 inhibitors in this patient cohort. The FGFR inhibitor nintedanib has recently been approved for treatment of lung adenocarcinoma and is currently evaluated for small cell lung cancer (SCLC). However, tumor recurrence due to development of nintedanib resistance might occur. Hence, we aimed at characterizing the molecular mechanisms underlying acquired nintedanib resistance in FGFR1-driven lung cancer. Chronic nintedanib exposure of the FGFR1-driven SCLC cell line DMS114 (DMS114/NIN) but not of two NSCLC cell lines induced massive overexpression of the multidrug-resistance transporter ABCB1. Indeed, we proved nintedanib to be both substrate and modulator of ABCB1-mediated efflux. Importantly, the oncogenic FGFR1 signaling axis remained active in DMS114/NIN cells while bioinformatic analyses suggested hyperactivation of the endothelin-A receptor (ETAR) signaling axis. Indeed, ETAR inhibition resensitized DMS114/NIN cells against nintedanib by downregulation of ABCB1 expression. PKC and downstream NFkappaB were identified as major downstream players in ETAR-mediated ABCB1 hyperactivation. Summarizing, ABCB1 needs to be considered as a factor underlying nintedanib resistance. Combination approaches with ETAR antagonists or switching to non-ABCB1 substrate FGFR inhibitors represent innovative strategies to manage nintedanib resistance in lung cancer. PMID- 27367031 TI - Leukocyte mitochondrial DNA copy number, anthropometric indices, and weight change in US women. AB - OBJECTIVES: To examine the association between leukocyte mitochondrial DNA copy number (mtCN) and different anthropometric indices as well as weight changes; and to compare mtCN and telomere length with respect to their associations with BMI and age. DESIGN: Population based cohort study. SETTING: Nurses' Health Study, an ongoing prospective cohort study of 121,700 nurses enrolled in 1976; in 1989-1990 a subset of 32,826 women provided blood samples. PARTICIPANTS: 1,700 disease-free US women from case-control studies nested within the Nurses' Health Study with mtCN and telomere length measured who also have anthropometric measurements. MAIN OUTCOME MEASURE: Relative mtCN and telomere lengths in peripheral blood leukocytes measured by quantitative real time polymerase chain reaction and various anthropometric measurements data from initial questionnaire. RESULTS: Leukocyte mtCN was inversely associated with current weight (LS means Q1-Q4: 0.07, 0.04, 0.03, -0.17; P trend =0.002), waist size (LS means Q1-Q4: 0.06, 0.05, -0.04, -0.06; P trend = 0.04), BMI (LS means normal light, normal heavy, overweight, pre-obese, obese: 0.11, -0.01, -0.04, 0.04, -0.25; P trend<0.0001), and waist-hip ratio (WHR) (LS means Q1-Q4: 0.06, 0.08, -0.04, -0.06; P trend = 0.03). A one-unit decrease in mtCN z score was equivalent to approximately 3.5 pounds of weight gain for an adult of 5'10''. In addition, weight gain was bi directionally and inversely associated with mtCN. Moreover, mtCN was strongly positively correlated with telomere length (LS means Q1-Q4: -0.02, 0.09, 0.11, 0.33; P trend <0.0001). MtCN was inversely associated with BMI even after adjusting for telomere length (P trend =0.003), while telomere length was not associated with BMI. On the other hand, telomere length was inversely associated with age after adjusting for mtCN (P trend =0.04), while mtCN was not associated with age. CONCLUSIONS: Our results provide compelling evidence for a potential bi directional temporal relationship between mitochondrial-mediated oxidative stress defense mechanisms and weight change. PMID- 27367034 TI - Comment on: outcomes of bariatric surgery in HIV-positive individuals. PMID- 27367032 TI - Capsaicin triggers autophagic cell survival which drives epithelial mesenchymal transition and chemoresistance in bladder cancer cells in an Hedgehog-dependent manner. AB - Bladder cancer (BC) is a common urologic tumor characterized by high risk of recurrence and mortality. Capsaicin (CPS), used as an intravesical drug for overactive bladder, was demonstrated to induce cell death in different cancer cells including BC cells.Here we found that treatment of high-grade BC cells with high dose of CPS triggers autophagy. Infact, the CPS treatment alters the redox homeostasis by inducing production of radicals, mitochondrial depolarization, alterations of ADP/ATP ratio and activation of AMPK pathway stimulating the autophagic process in BC cells. The inhibition of autophagy, by using the specific inhibitor bafilomycin A or Beclin 1 knock-down, enhanced the CPS-induced cell death, demonstrating that CPS-induced autophagy acts as a pro-survival process in BC cells. By using PCR arrays and FACS analysis, we found that the CPS treated BC cells displayed typical mesenchymal features of the epithelial mesenchymal transition (EMT) as elongated shape and over-expression of vimentin, alpha5 and beta1 integrin subunits, integrin-like kinase and the anti-apoptotic Bcl-2 proteins. Moreover, we demonstrated that CPS treatment stimulates upregulation of Dhh/Ptch2/Zeb2 members of the Hedgehog signaling pathway, increases CD24, VEGFA and TIMP1 and decreases CD44 and ALCAM mRNA expression levels. By PTCH2 knock-down we found that the Hedgehog signaling pathway is involved in the CPS-induced autophagy and EMT phenotype.Finally, we also showed that the CPS-resistant EMT-positive BC cells displayed an increased drug resistance to the cytotoxic effects of mitomycin C, gemcitabine and doxorubicine drugs commonly used in BC therapy. PMID- 27367033 TI - Analogs of the ATP-Sensitive Potassium (KATP) Channel Opener Cromakalim with in Vivo Ocular Hypotensive Activity. AB - ATP-sensitive potassium (KATP) channel openers have emerged as potential therapeutics for the treatment of glaucoma, lowering intraocular pressure (IOP) in animal models and cultured human anterior segments. We have prepared water soluble phosphate and dipeptide derivatives of the KATP channel opener cromakalim and evaluated their IOP lowering capabilities in vivo. In general, the phosphate derivatives proved to be more chemically robust and efficacious at lowering IOP with once daily dosing in a normotensive mouse model. Two of these phosphate derivatives were further evaluated in a normotensive rabbit model, with a significant difference in activity observed. No toxic effects on cell structure or alterations in morphology of the aqueous humor outflow pathway were observed after treatment with the most efficacious compound, (3S,4R)-2, suggesting that it is a strong candidate for development as an ocular hypotensive agent. PMID- 27367035 TI - Hematological disorders: a commonly unrecognized cause of acute stroke. AB - INTRODUCTION: Hematological disorders account for about 1.3% of all causes of acute stroke. This systematized review presents updated information on the implications of this category of heterogeneous diseases as a cause of stroke. AREAS COVERED: The most relevant aspects of the relationship between stroke and hematological disorders are reported. A high index of suspicion is needed in young stroke patients, patients with recurrent stroke of undetermined cause, and in patients with prior history of venous thrombosis to identify a potential hematological disorder as the definitive etiology of stroke Expert commentary: Stroke can be the presenting manifestation of a specific hematological disease or may appear as a complication in the course of hematological disorders. It is important to make a correct diagnosis of the underlying hematological disorder in order to treat stroke patients promptly and appropriately as well as to establish the optimal secondary prevention strategy for recurrent vascular cerebral disease. PMID- 27367036 TI - Controlled Ring-Opening of Siloxydifluorocyclopropanes for Carbocyclization: Synthesis of Difluorocyclopentenones. AB - A highly controlled ring opening of siloxydifluorocyclopropanes, formed by nBuN4Br-catalyzed difluorocyclopropanation of methyl vinyl ketones bearing a beta alkylthio group by using TMSCF2Br as a unique difluorocarbene source, results in metal difluorohomoenolates with assistance of copper or silver followed by an intramolecular addition and elimination reaction leading to alpha-gem difluorocyclopentenones efficiently. PMID- 27367037 TI - LotuS: an efficient and user-friendly OTU processing pipeline. AB - BACKGROUND: 16S ribosomal DNA (rDNA) amplicon sequencing is frequently used to analyse the structure of bacterial communities from oceans to the human microbiota. However, computational power is still a major bottleneck in the analysis of continuously enlarging metagenomic data sets. Analysis is further complicated by the technical complexity of current bioinformatics tools. RESULTS: Here we present the less operational taxonomic units scripts (LotuS), a fast and user-friendly open-source tool to calculate denoised, chimera-checked, operational taxonomic units (OTUs). These are the basis to generate taxonomic abundance tables and phylogenetic trees from multiplexed, next-generation sequencing data (454, illumina MiSeq and HiSeq). LotuS is outstanding in its execution speed, as it can process 16S rDNA data up to two orders of magnitude faster than other existing pipelines. This is partly due to an included stand alone fast simultaneous demultiplexer and quality filter C++ program, simple demultiplexer (sdm), which comes packaged with LotuS. Additionally, we sequenced two MiSeq runs with the intent to validate future pipelines by sequencing 40 technical replicates; these are made available in this work. CONCLUSION: We show that LotuS analyses microbial 16S data with comparable or even better results than existing pipelines, requiring a fraction of the execution time and providing state-of-the-art denoising and phylogenetic reconstruction. LotuS is available through the following URL: http://psbweb05.psb.ugent.be/lotus . PMID- 27367038 TI - Estimating self-reported sex practices, drug use, depression, and intimate partner violence among MSM in China: a comparison of three recruitment methods. AB - Men who have sex with men (MSM) are the group at highest risk for HIV in China. Researchers have used various recruitment methods to reach this population hidden from the hetero-normative culture. To inform future recruitment strategies, we compared estimates of socio-demographic characteristics, HIV risk behaviors, depression, and intimate partner violence (IPV) across three samples of MSM and money boys in Shanghai, China. Data were collected from three community-based samples of MSM and money boys (n = 1352) recruited via respondent-driven sampling (RDS) (n = 404), community popular opinion leaders (CPOL) (n = 385), and Internet and venue-based sampling (VBS) (n = 546). Different recruitment methods generated samples with statistically significant differences among a number of socio demographic characteristics, sexual behaviors, drug use, depression scores, and exposure to IPV. Specifically, RDS participants had lower education (p = .002), income levels (p < .001), and were more likely to report condomless sex with a woman (p < .001). CPOL participants were younger (p < .001), more likely to report lifetime condomless anal sex (p = .009), more than 10 male partners in the past 30 days (p < .001), and were less likely to experience violence by a male intimate partner (p = .001). VBS participants had lowest depression score (p = .005) and were more likely to report lifetime drug use (p = .003). Our findings reinforce that each recruitment method may reach a sub-group of MSM with a specific risk profile, so multiple methods may be needed to obtain a representative sample of MSM. Interventions may use specific recruitment methods to target certain segments of the MSM population. PMID- 27367039 TI - Deep molecular responses for treatment-free remission in chronic myeloid leukemia. AB - Several clinical trials have demonstrated that some patients with chronic myeloid leukemia in chronic phase (CML-CP) who achieve sustained deep molecular responses on tyrosine kinase inhibitor (TKI) therapy can safely suspend therapy and attempt treatment-free remission (TFR). Many TFR studies to date have enrolled imatinib treated patients; however, the feasibility of TFR following nilotinib or dasatinib has also been demonstrated. In this review, we discuss available data from TFR trials and what these data reveal about the molecular biology of TFR. With an increasing number of ongoing TFR clinical trials, TFR may become an achievable goal for patients with CML-CP. PMID- 27367041 TI - Drawing the Line in Risk-Reducing Gynecologic Surgery in Women With a BRCA Mutation. PMID- 27367040 TI - Drug disposition before and after gastric bypass: fenofibrate and posaconazole. AB - AIMS: Roux-en-Y gastric bypass (RYGB) alters the anatomical structure of the gastrointestinal tract, which can result in alterations in drug disposition. The aim of the present study was to evaluate the oral disposition of two compounds belonging to the Biopharmaceutical Classification System Class II - fenofibrate (bile salt-dependent solubility) and posaconazole (gastric pH-dependent dissolution) - before and after RYGB in the same individuals. METHODS: A single dose pharmacokinetic study with two model compounds - namely, 67 mg fenofibrate (Lipanthyl(r)) and 400 mg posaconazole (Noxafil(r)) - was performed in 12 volunteers pre- and post-RYGB. After oral administration, blood samples were collected at different time points up to 48 h after administration. Plasma concentrations were determined by high-performance liquid chromatography in order to calculate the area under the concentration-time curve up to 48 h (AUC0-48 h ), the peak plasma concentration (Cmax) and the time to reach peak concentration (Tmax ). RESULTS: After administration of fenofibrate, no relevant differences in AUC0-48 h , Cmax and Tmax between the pre- and postoperative setting were observed. The geometric mean of the ratio of AUC0-48 h post/pre-RYGB for fenofibrate was 1.10 [95% confidence interval (CI) 0.87, 1.40; P = 0.40]. For posaconazole, an important decrease in AUC0-48 h and Cmax following RYGB was shown; the geometric mean of the AUC0-48 h post/pre-RYGB ratio was 0.68 (95% CI 0.48, 0.96; P = 0.03) and the geometric mean of the Cmax pre/post-RYGB ratio was 0.60 (95% CI 0.39, 0.94; P = 0.03). The decreased exposure of posaconazole could be explained by the increased gastric pH and accelerated gastric emptying of fluids post-RYGB. No difference for Tmax was observed. CONCLUSIONS: The disposition of fenofibrate was not altered after RYGB, whereas the oral disposition of posaconazole was significantly decreased following RYGB. PMID- 27367042 TI - Studies toward understanding the SAR around the sulfoximine moiety of the sap feeding insecticide sulfoxaflor. AB - BACKGROUND: The discovery of sulfoxaflor (IsoclastTM active) stemmed from a novel scaffold-based approach toward identifying bioactive molecules. It exhibits broad spectrum control of many sap-feeding insect pests, including aphids, whiteflies, hoppers and Lygus. Systematic modifications of the substituents flanking each side of the sulfoximine moiety were carried out to determine whether these changes would improve potency. RESULTS: Structure-activity relationship (SAR) studies showed that, with respect to the methylene linker, both mono- and disubstitution with alkyl groups of varying sizes as well as cyclic analogs exhibited excellent control of cotton aphids. However, against green peach aphids a decrease in activity was observed with substituents larger than ethyl as well as larger cycloalkyl groups. At the terminal tail there appeared to be a narrow steric tolerance as well, with linear groups or small rings more active against green peach aphids than bulkier groups. CONCLUSION: A novel series of compounds exploring the substituents flanking the sulfoximine moiety of sulfoxaflor were prepared and tested for bioactivity against cotton aphids and green peach aphids. SAR studies indicated that a decrease in green peach aphid potency was observed at the methylene linker as well as at the terminal tail with bulkier substituents. A quantitative structure-activity relationship analysis of the compounds revealed significant correlation of activity with two molecular descriptors, vol (volume of a molecule) and GCUT_SMR_3 (molar refractivity). This predictive model helps to explain the observed activity with the various substituents. (c) 2016 Society of Chemical Industry. PMID- 27367043 TI - Screening Criteria Improve Access to Palliative Care in the PICU. AB - OBJECTIVES: To test the ability of palliative care screening criteria to improve access to palliative care services in the PICU and examine the association between palliative care team involvement and ICU and hospital length of stay. DESIGN: Prospective interventional quality improvement study. SETTING: PICU at a quaternary academic medical center. PATIENTS: All patients admitted to the PICU who met criteria for palliative care referral over a 9-month period. INTERVENTION: Consensus palliative care consultation criteria were created by pediatric critical care medicine and palliative care providers, and palliative care referral was encouraged for all PICU patients meeting criteria. MEASUREMENTS AND MAIN RESULTS: Palliative care referral rates increased significantly after screening criteria implementation. We identified 100 patients who were eligible for palliative care services, and referrals were made for 70 patients (70%). Patients were divided into three groups based on palliative care status: patients new to the palliative care team, patients with an existing palliative care relationship, and patients who did not have a palliative care referral. By the end of study, patients who had an existing relationship with the palliative care team were more likely to still be alive and to have limitations of medical interventions in place, whereas patients who did not have a palliative care referral were more likely to be deceased and to have died in the PICU. After correcting for other factors, including severity of illness, patients who were new to the palliative care team experienced greater delay in palliative care referral and had significantly longer PICU and hospital length of stay than those who were already known to the palliative care team. CONCLUSIONS: Palliative care screening criteria are effective tools for improving access to palliative care services in the PICU; however, widespread adoption may produce a significant increase in palliative care demand. The association between an existing palliative care relationship and reduction in resource utilization deserves further investigation as does the perceived benefit of palliative care involvement in the patient, family, and staff experience. PMID- 27367044 TI - Children and Young Adults Who Received Tracheostomies or Were Initiated on Long Term Ventilation in PICUs. AB - OBJECTIVES: To characterize patients who received tracheostomies for airway compromise or were initiated on long-term ventilation for chronic respiratory failure in PICUs and to examine variation in the incidence of initiation, patient characteristics, and modalities across sites. DESIGN: Retrospective cross sectional analysis. SETTINGS: Seventy-three North American PICUs that participated in the Virtual Pediatric Systems, LLC. PATIENTS: PICU patients admitted between 2009 and 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 115,437 PICU patients, 1.8% received a tracheostomy or were initiated on long-term ventilation; 1,034 received a tracheostomy only, 717 were initiated on invasive ventilation, and 381 were initiated on noninvasive ventilation. Ninety percent had substantial chronic conditions and comorbidities, including more than 50% with moderate or worse cerebral disability upon discharge. Seven percent were initiated after a catastrophic injury/event. Across sites, there was variation in incidence of tracheotomy and initiation of long term ventilation, ranging from 0% to 4.6%. There also was variation in patient characteristics, time to tracheotomy, number of extubations prior to tracheostomy, and the use of invasive ventilation versus noninvasive ventilation. CONCLUSIONS: Although the PICU incidence of initiation of tracheostomies and long term ventilation was relatively uncommon, it suggests that thousands of children and young adults receive these interventions each year in North American PICUs. The majority of them have conditions and comorbidities that impose on-going care needs, beyond those required by artificial airways and long-term ventilation themselves. PMID- 27367045 TI - A School-Based Injury Prevention Program to Reduce Sport Injury Risk and Improve Healthy Outcomes in Youth: A Pilot Cluster-Randomized Controlled Trial. AB - OBJECTIVE: To examine a school-based high-intensity neuromuscular training (NMT) program in reducing sport injury risk and improving fitness in youth. PARTICIPANTS: Students (ages 11-15) (n = 725) in physical education (PE) classes were randomized by school to intervention or control groups. INTERVENTION: A 12 week high-intensity NMT program (including aerobic, strength, balance, and agility components) was designed to reduce sport injury risk and improve measures of fitness. The control program was a standard of practice warm-up (including running and stretching). RESULTS: A Poisson regression model using an intent-to treat analysis demonstrated a reduced risk of sport injury: incidence rate ratio (IRR)all injury = 0.30 (95% CI, 0.19-0.49), IRRlower extremity injury = 0.31 (95% CI, 0.19-0.51), IRRankle sprain injury = 0.27 (95% CI, 0.15-0.50), and IRRknee sprain injury = 0.36 (95% CI, 0.13-0.98). A change in waist circumference: -0.99 centimeters (95% CI, -1.84 to -0.14) and an increase in indirect measures of aerobic fitness: 1.28 mL.kg.min (95% CI, 0.66-1.90) in the intervention school compared with the control school also occurred. CONCLUSIONS: A NMT program in junior high school PE class was efficacious in reducing sport-related injury and improving measures of adiposity and fitness in the intervention group. PMID- 27367046 TI - High-throughput DNA methylation analysis in anorexia nervosa confirms TNXB hypermethylation. AB - OBJECTIVES: Patients with anorexia nervosa (AN) are ideally suited to identify differentially methylated genes in response to starvation. METHODS: We examined high-throughput DNA methylation derived from whole blood of 47 females with AN, 47 lean females without AN and 100 population-based females to compare AN with both controls. To account for different cell type compositions, we applied two reference-free methods (FastLMM-EWASher, RefFreeEWAS) and searched for consensus CpG sites identified by both methods. We used a validation sample of five monozygotic AN-discordant twin pairs. RESULTS: Fifty-one consensus sites were identified in AN vs. lean and 81 in AN vs. population-based comparisons. These sites have not been reported in AN methylation analyses, but for the latter comparison 54/81 sites showed directionally consistent differential methylation effects in the AN-discordant twins. For a single nucleotide polymorphism rs923768 in CSGALNACT1 a nearby site was nominally associated with AN. At the gene level, we confirmed hypermethylated sites at TNXB. We found support for a locus at NR1H3 in the AN vs. lean control comparison, but the methylation direction was opposite to the one previously reported. CONCLUSIONS: We confirm genes like TNXB previously described to comprise differentially methylated sites, and highlight further sites that might be specifically involved in AN starvation processes. PMID- 27367047 TI - Mainstreaming Naloxone Through Coprescription to Patients Receiving Long-Term Opioid Therapy for Chronic Pain. PMID- 27367048 TI - Phenotypic Characterization and Genetic Dissection of Growth Period Traits in Soybean (Glycine max) Using Association Mapping. AB - The growth period traits are important traits that affect soybean yield. The insights into the genetic basis of growth period traits can provide theoretical basis for cultivated area division, rational distribution, and molecular breeding for soybean varieties. In this study, genome-wide association analysis (GWAS) was exploited to detect the quantitative trait loci (QTL) for number of days to flowering (ETF), number of days from flowering to maturity (FTM), and number of days to maturity (ETM) using 4032 single nucleotide polymorphism (SNP) markers with 146 cultivars mainly from Northeast China. Results showed that abundant phenotypic variation was presented in the population, and variation explained by genotype, environment, and genotype by environment interaction were all significant for each trait. The whole accessions could be clearly clustered into two subpopulations based on their genetic relatedness, and accessions in the same group were almost from the same province. GWAS based on the unified mixed model identified 19 significant SNPs distributed on 11 soybean chromosomes, 12 of which can be consistently detected in both planting densities, and 5 of which were pleotropic QTL. Of 19 SNPs, 7 SNPs located in or close to the previously reported QTL or genes controlling growth period traits. The QTL identified with high resolution in this study will enrich our genomic understanding of growth period traits and could then be explored as genetic markers to be used in genomic applications in soybean breeding. PMID- 27367049 TI - Distribution of Cytomegalovirus Genotypes among Neonates Born to Infected Mothers in Islamabad, Pakistan. AB - BACKGROUND: Congenital cytomegalovirus (cCMV) infection contributes to considerable long-term sequelae in neonates and children all over the world. The association between viral genotypes and severity of clinical cytomegalovirus (CMV) infection is yet to be defined. The objective of this study was to find the impact of active CMV infection during pregnancy and the clinical significance of genotypes in neonates with congenital cytomegalovirus infections in Pakistan. METHODS: A total of 409 blood samples from pregnant women seeking health care services at the two antenatal hospitals of Islamabad during January to December 2012 were tested by ELISA and nested-PCR. Pregnant women with active infection (detected as IgM positive, PCR positive or positive on both assays) were followed until delivery, to detect the outcome of overt cCMV infection in neonates. Genetic characterization of CMV strains was performed by sequence analysis of envelope glycoproteins: gB, gN and gH to detect the contributing CMV genotypes. RESULTS: The seroprevalence of anti-CMV IgG and IgM was 97.5% (399 out of 409) and 12.7% (52 out of 409), respectively, while 20% (82/409) pregnant women were found positive for CMV DNA by PCR. Logistic regression analysis showed a significant association of active infection with parity [OR = 2.56, 95% CI = 1.82 2.62, p = 0.04], febrile illness [OR = 1.84, 95% CI = 1.76-3.65, p = 0.01] and jaundice [OR = 22.5, 95% CI = 4.53-85.02, p = 0.002]. We were able to isolate virus in 41 out of 70 neonates; 36.6% (15 out of 41) of them were symptomatic at birth while 63.4% (26 out of 41) were asymptomatic. The most prominent clinical feature observed in symptomatic neonates was hepatosplenomegaly (26.6%; 4 out of 15). All three genotypes gB, gN and gH were found with the highest frequency of gB1 genotype, found in 75% infants with hepatic damage. Phylogenetic analysis of Pakistani strains showed 96%-100% homology to their prototype strains. CONCLUSIONS: Active CMV infection during pregnancy is a major cause of congenital CMV infection with comparable distribution of all three genotypes: gB, gN and gH in symptomatic and asymptomatic neonates. Our findings emphasize to conduct a comprehensive large scale survey and introduction of country wide routine screening at maternity clinics for early diagnosis of CMV to reduce its associated devastating outcomes. PMID- 27367050 TI - Induction of Excess Centrosomes in Neural Progenitor Cells during the Development of Radiation-Induced Microcephaly. AB - The embryonic brain is one of the tissues most vulnerable to ionizing radiation. In this study, we showed that ionizing radiation induces apoptosis in the neural progenitors of the mouse cerebral cortex, and that the surviving progenitor cells subsequently develop a considerable amount of supernumerary centrosomes. When mouse embryos at Day 13.5 were exposed to gamma-rays, brains sizes were reduced markedly in a dose-dependent manner, and these size reductions persisted until birth. Immunostaining with caspase-3 antibodies showed that apoptosis occurred in 35% and 40% of neural progenitor cells at 4 h after exposure to 1 and 2 Gy, respectively, and this was accompanied by a disruption of the apical layer in which mitotic spindles were positioned in unirradiated mice. At 24 h after 1 Gy irradiation, the apoptotic cells were completely eliminated and proliferation was restored to a level similar to that of unirradiated cells, but numerous spindles were localized outside the apical layer. Similarly, abnormal cytokinesis, which included multipolar division and centrosome clustering, was observed in 19% and 24% of the surviving neural progenitor cells at 48 h after irradiation with 1 and 2 Gy, respectively. Because these cytokinesis aberrations derived from excess centrosomes result in growth delay and mitotic catastrophe-mediated cell elimination, our findings suggest that, in addition to apoptosis at an early stage of radiation exposure, radiation-induced centrosome overduplication could contribute to the depletion of neural progenitors and thereby lead to microcephaly. PMID- 27367052 TI - Special Section Guest Editorial: Optical Diagnostic and Biophotonic Methods from Bench to Bedside. PMID- 27367051 TI - A Wearable Goggle Navigation System for Dual-Mode Optical and Ultrasound Localization of Suspicious Lesions: Validation Studies Using Tissue-Simulating Phantoms and an Ex Vivo Human Breast Tissue Model. AB - Surgical resection remains the primary curative treatment for many early-stage cancers, including breast cancer. The development of intraoperative guidance systems for identifying all sites of disease and improving the likelihood of complete surgical resection is an area of active ongoing research, as this can lead to a decrease in the need of subsequent additional surgical procedures. We develop a wearable goggle navigation system for dual-mode optical and ultrasound imaging of suspicious lesions. The system consists of a light source module, a monochromatic CCD camera, an ultrasound system, a Google Glass, and a host computer. It is tested in tissue-simulating phantoms and an ex vivo human breast tissue model. Our experiments demonstrate that the surgical navigation system provides useful guidance for localization and core needle biopsy of simulated tumor within the tissue-simulating phantom, as well as a core needle biopsy and subsequent excision of Indocyanine Green (ICG)-fluorescing sentinel lymph nodes. Our experiments support the contention that this wearable goggle navigation system can be potentially very useful and fully integrated by the surgeon for optimizing many aspects of oncologic surgery. Further engineering optimization and additional in vivo clinical validation work is necessary before such a surgical navigation system can be fully realized in the everyday clinical setting. PMID- 27367053 TI - Short-Acting Gas Tamponade with Strict Face-Down Posturing for the Treatment of Idiopathic Macular Hole. AB - PURPOSE: A retrospective consecutive case series to evaluate the safety and efficacy of 25 gauge pars plana vitrectomy, ILM peeling, 20% SF6 gas tamponade and strict posturing for the treatment of idiopathic full-thickness macular holes. METHODS: We report the results of 106 consecutive eyes that underwent standard 25-gauge pars plana vitrectomy, brilliant peel-assisted internal limiting membrane peel, fluid:gas exchange with 20% SF6 and strict posturing for one week. All patients were followed up at one week, one month, three months, and nine months postoperatively. Biomicroscopy at day 1 and biomicroscopy and OCT at week 1, months 1, 3, and 9 were used to assess macular hole status postoperatively. Pre- and postoperative logMAR visual acuity was compared. RESULTS: The macular hole was closed in 102/106 eyes postoperatively (96.2%). Four eyes showed unclosed macular holes and underwent additional SF6 intravitreal injection and strict posturing for 10 days. All macular holes were eventually closed without the need of a second surgical procedure. Mean visual acuity improved from 0.63 logMAR preoperatively to 0.39 logMAR postoperatively. One case of retinal toxicity was reported due to accidental intravitreal injection of antibiotic. CONCLUSIONS: 25-gauge vitrectomy, ILM peel, and short-acting gas tamponade are highly effective for the treatment of macular holes. Additional intravitreal gas injection followed by strict posturing seems to be a simple and effective treatment for unclosed holes. PMID- 27367054 TI - Hepatitis B immunity in the pediatric liver transplant population. AB - PURPOSE OF REVIEW: Hepatitis B virus (HBV) infection contributes significantly to vaccine-preventable disease related deaths, and insufficient HBV immunity may have unique implications for the pediatric liver transplant population. This article reviews the significance of HBV infection and the vaccination and screening measures needed to achieve adequate HBV immunity in these children. RECENT FINDINGS: HBV non-immunity among transplant candidates is higher than expected, even after appropriate completion of the vaccine series. Annual measurement of quantifiable HBV surface antibody in this vulnerable group should guide administration of booster and/or re-vaccination, improving immunoprotection from this potentially deadly hepatotropic virus. The liver plays a vital role in immune regulation; it induces immune tolerance and competence and both clears antigens from the circulation and generates liver-primed memory cells through antigen presentation via hepatic scavenger cells. Lymphocyte populations are depleted in patients with liver disease. SUMMARY: Immunity provided during early childhood against HBV infection is important to both pediatric liver transplant candidates and aging recipients. Appropriate vaccination and achievement of adequate immunity pre-transplant and post-transplant is critical. The field of pediatric transplantation is ripe for functional cellular and humoral immunity studies that examine factors which predict poor immune response to childhood vaccines, particularly HBV. PMID- 27367055 TI - Potential Role of In Vivo Confocal Microscopy for Imaging Corneal Nerves in Transthyretin Familial Amyloid Polyneuropathy. AB - IMPORTANCE: Small fiber neuropathy (SFN) is an important feature of transthyretin familial amyloid polyneuropathy (TTR-FAP). A practical and objective method for the clinical evaluation of SFN is needed to improve the management of this disease. In vivo confocal microscopy (IVCM) of the corneal nerves, a rapid noninvasive technique, may be used as a surrogate marker of SFN. OBJECTIVE: To determine the correlation of SFN with IVCM in patients with TTR-FAP. DESIGN, SETTING, AND PARTICIPANTS: A prospective, single-center, cross-sectional controlled study was conducted at the French National Reference Center for TTR FAP from June 1, 2013, to June 30, 2014. Fifteen patients with TTR-FAP underwent a complete neurologic examination, including Neuropathy Impairment Score of the Lower Limbs, hand grip strength, and evaluation of vegetative dysfunction, as well as electrophysiologic studies (nerve conduction and electrochemical skin conductance) and intraepidermal nerve fiber density quantification. Patients and 15 controls (matched for age and sex) underwent ophthalmologic assessments, including corneal esthesiometry and IVCM. MAIN OUTCOMES AND MEASURES: Correlation of corneal nerve fiber length (CNFL) with the severity of SFN. RESULTS: Of the 15 patients enrolled in the study, 6 were women (40%); mean (SD) age was 54.4 [13.7] years. The CNFL was shorter in the patients than in controls (13.08 vs 17.57 mm/mm2; difference of 4.49 [95% CI, 0.72 to 8.27]; P = .02). The patients' CNFL correlated with the severity of both autonomic neuropathy assessed by the Compound Autonomic Dysfunction Test (rs = 0.66 [95% CI, 0.22 to 0.87]; P = .008) or electrochemical skin conductance (rs = 0.80 [95% CI, 0.50 to 0.93]; P < .001) and sensorimotor neuropathy assessed using the Neuropathy Impairment Score of the Lower Limbs (rs = -0.58 [95% CI, -0.84 to -0.11]; P = .02). Patients with altered sensory nerve action potentials and intraepidermal nerve fiber density had a shorter CNFL (P = .04 and P = .02, respectively). The CNFL could be measured in all patients compared with sensory nerve action potentials (11 patients [73%; 95% CI, 44% to 92%]; P < .001) and intraepidermal nerve fiber density (4 patients [27%; 95% CI, 8% to 55%]; P < .001). CONCLUSIONS AND RELEVANCE: In these 15 patients with TTR-FAP, IVCM measurement permitted rapid, noninvasive evaluation of small-fiber alterations in patients and could be used to assess SFN in this setting. The CNFL could be measured in all patients, thus avoiding the floor effect seen with other neuropathy measures. Longitudinal studies with more cases evaluated are needed to define the place of IVCM in monitoring patients with TTR FAP. PMID- 27367056 TI - Growth Retardation and Altered Isotope Composition As Delayed Effects of PCB Exposure in Daphnia magna. AB - Trophic magnification factor (TMF) analysis employs stable isotope signatures to derive biomagnification potential for environmental contaminants. This approach relies on species delta(15)N values aligning with their trophic position (TP). This, however, may not always be true, because toxic exposure can alter growth and isotope allocation patterns. Here, effects of PCB exposure (mixture of PCB18, PCB40, PCB128, and PCB209) on delta(15)N and delta(13)C as well as processes driving these effects were explored using the cladoceran Daphnia magna. A two part experiment assessed effects of toxic exposure during and after exposure; juvenile daphnids were exposed during 3 days (accumulation phase) and then allowed to depurate for 4 days (depuration phase). No effects on survival, growth, carbon and nitrogen content, and stable isotope composition were observed after the accumulation phase, whereas significant changes were detected in adults after the depuration phase. In particular, a significantly lower nitrogen content and a growth inhibition were observed, with a concomitant increase in delta(15)N (+0.1 0/00) and decrease in delta(13)C (-0.1 0/00). Although of low magnitude, these changes followed the predicted direction indicating that sublethal effects of contaminant exposure can lead to overestimation of TP and hence underestimated TMF. PMID- 27367057 TI - Chlorogenic acid inhibits cholestatic liver injury induced by alpha naphthylisothiocyanate: involvement of STAT3 and NFkappaB signalling regulation. AB - OBJECTIVES: Chlorogenic acid (CGA) is one of the most widely consumed polyphenols in diets and is recognized to be a natural hepatoprotective agent. Here, we evaluated the protective effect and the potential mechanism of CGA against alpha naphthylisothiocyanate (ANIT)-induced cholestasis and liver injury. METHODS: Twenty-five male 129/Sv mice were administered with CGA, and ANIT challenge was performed at 75 mg/kg on the 4th day. Blood was collected and subjected to biochemical analysis; the liver tissues were examined using histopathological analysis and signalling pathways. KEY FINDINGS: Chlorogenic acid almost totally attenuated the ANIT-induced liver damage and cholestasis, compared with the ANIT group. Dose of 50 mg/kg of CGA significantly prevented ANIT-induced changes in serum levels of alanine aminotransferase, alkaline phosphatases, total bile acid, direct bilirubin, indirect bilirubin (5.3-, 6.3-, 18.8-, 158-, 41.4-fold, P<0.001) and aspartate aminotransferase (4.6-fold, P<0.01). Expressions of the altered bile acid metabolism and transport-related genes were normalized by cotreatment with CGA. The expressions of interleukin 6, tumour necrosis factor alpha and suppressor of cytokine signalling 3 were found to be significantly decreased (1.2-fold, ns; 11.0-fold, P<0.01; 4.4-fold, P<0.05) in the CGA/ANIT group. Western blot revealed that CGA inhibited the activation and expression of signal transducer and activator of transcription 3 and NFkappaB. CONCLUSIONS: These data suggest that CGA inhibits both ANIT-induced intrahepatic cholestasis and the liver injury. This protective effect involves down-regulation of STAT3 and NFkappaB signalling. PMID- 27367058 TI - The signaling pathway of dopamine D2 receptor (D2R) activation using normal mode analysis (NMA) and the construction of pharmacophore models for D2R ligands. AB - G-protein-coupled receptors (GPCRs) are targets of more than 30% of marketed drugs. Investigation on the GPCRs may shed light on upcoming drug design studies. In the present study, we performed a combination of receptor- and ligand-based analysis targeting the dopamine D2 receptor (D2R). The signaling pathway of D2R activation and the construction of universal pharmacophore models for D2R ligands were also studied. The key amino acids, which contributed to the regular activation of the D2R, were in detail investigated by means of normal mode analysis (NMA). A derived cross-correlation matrix provided us an understanding of the degree of pair residue correlations. Although negative correlations were not observed in the case of the inactive D2R state, a high degree of correlation appeared between the residues in the active state. NMA results showed that the cytoplasmic side of the TM5 plays a significant role in promoting of residue residue correlations in the active state of D2R. Tracing motions of the amino acids Arg219, Arg220, Val223, Asn224, Lys226, and Ser228 in the position of the TM5 are found to be critical in signal transduction. Complementing the receptor based modeling, ligand-based modeling was also performed using known D2R ligands. The top-scored pharmacophore models were found as 5-sited (AADPR.671, AADRR.1398, AAPRR.3900, and ADHRR.2864) hypotheses from PHASE modeling from a pool consisting of more than 100 initial candidates. The constructed models using 38 D2R ligands (in the training set) were validated with 15 additional test set compounds. The resulting model correctly predicted the pIC50 values of an additional test set compounds as true unknowns. PMID- 27367059 TI - The Role of Surface Viscosity in the Escape Mechanism of the Stenus Beetle. AB - Beetles of the species Stenus comma live and hunt close to ponds and rivers, where they occasionally fall on the water surface. To escape this jeopardized state, the beetle developed a strategy relying on the excretion of a secretion containing the substances stenusine and norstenusine. They reduce surface tension and propel the bug to the saving river bank. These substances were synthesized and analyzed with respect to their equilibrium and dynamic adsorption properties at the air-water interface (pH 7, 23 +/- 1 degrees C). The surface dilatational rheological characteristics in a frequency range from 2 to 500 Hz at molar bulk concentrations of 20.6 mmol L(-1) were studied using the oscillating bubble technique. Both alkaloids formed surface viscoelastic adsorption layers. The frequency dependence of the surface dilatational modulus E could successfully be described by the extended Lucassen-van den Tempel model accounting for a nonzero intrinsic surface viscosity kappa. The findings confirmed a dual purpose of the spreading alkaloids in the escape mechanism of the Stenus beetle. Next to generating a surface pressure, a transition to surface viscoelastic behavior of the adsorbed layers was observed. PMID- 27367060 TI - High-power 2.04 MUm laser in an ultra-compact Ho-doped lead germanate fiber. AB - A highly Ho-doped single-mode lead germanate glass fiber is developed for compact ~2 MUm lasers. Over 600 mW of laser output operating at 2.04 MUm is demonstrated in a 2 cm-long active fiber. The slope efficiency reaches ~34.9% with respect to the launched 1.94 MUm laser pump power. To the best of our knowledge, this is the highest laser output power demonstrated within a few centimeters of a Ho-doped fiber. This result shows that the fiber is highly promising for high-power single frequency laser applications. PMID- 27367061 TI - Optics of a single ultrasharp groove in metal. AB - Optical properties of a single ultrasharp groove of subwavelength width cut in an otherwise flat metal surface are examined theoretically. We calculate optical extinction, scattering, and absorption cross-section spectra for a wide range of groove profiles, establishing several fundamental trends. As grooves are made sharper, amplitudes of oscillations in cross-section spectra and their period decrease, while the absorption level increases, leading eventually to efficient broadband (nonresonant) absorption. Oscillations in scattering spectra are generally more pronounced than those in corresponding absorption spectra. For ultrasharp grooves, oscillations in all spectra can be suppressed by increasing the groove depth. Finally, the level of absorption relative to that of scattering increases as the top groove width decreases, a trend that is analogous to that found when decreasing the size of metal nanoparticles. PMID- 27367062 TI - Optical Cherenkov radiation in overmoded microresonators. AB - We show that an optical analog of Cherenkov radiation (dispersive wave) is observable in a nonlinear microring resonator generating Kerr frequency comb and containing linearly interacting families of equidistant modes. The radiation results from disruptions in the frequency dependent group velocity dispersion of the pumped cavity modes and is emitted into different mode families of the resonator. This effect reveals itself as a dispersive shaped structure in the spectral envelope of the frequency comb. We found that the dips in the comb spectrum correspond to peaks of the emission of the power in the other mode families of the resonator. The spectrum of the combs that includes both mode families does not have any dips, but peaks and resembles the Cherenkov radiation spectra frequently observed in Kerr comb systems. This Letter shows that a correct description of the Kerr comb in presence of mode anti-crossings should take into account not only the pumped mode family with modified dispersion parameter, but also the modes of the interacting families. PMID- 27367063 TI - Optical magnetism and optical activity in nonchiral planar plasmonic metamaterials. AB - We investigate optical magnetism and optical activity in a simple planar metamolecule composed of double U-shaped metal split ring resonators (SRRs) twisted by 90 degrees with respect to one another. Compared to a single SRR, the resonant energy levels are split and strong magnetic response can be observed due to inductive and conductive coupling. More interestingly, the nonchiral structures exhibit strong optical gyrotropy (1100 degrees /lambda) under oblique incidence, benefiting from the strong electromagnetic coupling. A chiral molecule model is proposed to shed light on the physical origin of optical activity. These artificial chiral metamaterials could be utilized to control the polarization of light and promise applications in enantiomer sensing-based medicine, biology, and drug development. PMID- 27367064 TI - Excitation of Bloch-like surface waves in quasi-crystals and aperiodic dielectric multilayers. AB - The existence of Bloch surface waves in periodic dielectric multilayer structures with a surface defect is well known. Not yet recognized is that quasi-crystals and aperiodic dielectric multilayers can also support Bloch-like surface waves. In this work, we numerically show the excitation of Bloch-like surface waves in Fibonacci quasi-crystals and Thue-Morse aperiodic dielectric multilayers using the prism coupling method. We report improved surface electric field intensity and penetration depth of Bloch-like surface waves in the air side in such structures compared to their periodic counterparts. PMID- 27367065 TI - Two-dimensional chi2 solitons generated by the downconversion of Airy waves. AB - Conversion of truncated Airy waves (AWs) carried by the second-harmonic (SH) component into axisymmetric chi2 solitons is considered in a 2D system with quadratic nonlinearity. The spontaneous conversion is driven by the parametric instability of the SH wave. The input in the form of the AW vortex is also considered. As a result, one, two, or three stable solitons emerge in a well defined form, unlike the recently studied 1D setting, where the picture is obscured by radiation jets. Shares of the total power captured by the emerging solitons and conversion efficiency are found as functions of parameters of the AW input. PMID- 27367066 TI - Congestion estimation technique in the optical network unit registration process. AB - We present a congestion estimation technique (CET) to estimate the optical network unit (ONU) registration success ratio for the ONU registration process in passive optical networks. An optical line terminal (OLT) estimates the number of collided ONUs via the proposed scheme during the serial number state. The OLT can obtain congestion level among ONUs to be registered such that this information may be exploited to change the size of a quiet window to decrease the collision probability. We verified the efficiency of the proposed method through simulation and experimental results. PMID- 27367067 TI - 2D wave-front shaping in optical superlattices using nonlinear volume holography. AB - Nonlinear volume holography is employed to realize arbitrary wave-front shaping during nonlinear processes with properly designed 2D optical superlattices. The concept of a nonlinear polarization wave in nonlinear volume holography is investigated. The holographic imaging of irregular patterns was performed using 2D LiTaO3 crystals with fundamental wave propagating along the spontaneous polarization direction, and the results agree well with the theoretical predictions. This Letter not only extends the application area of optical superlattices, but also offers an efficient method for wave-front shaping technology. PMID- 27367068 TI - Control over photo-inscription and thermal annealing to obtain high-quality Bragg gratings in doped PMMA optical fibers. AB - Bragg gratings are photo-inscribed in trans-4-stilbenemethanol doped PMMA fibers using a 325 nm He-Cd laser and a phase mask. Two distinct behaviors are reported depending on the laser power density. In the high-density regime with 637 mW/mm2, the grating reflectivity is stable over time after the writing process, but the reflected spectrum is of limited quality, as the grating length is limited to the laser width (1.2 mm). The beam is then enlarged to 6 mm, decreasing the power density to 127 mW/mm2. In this case, the grating reflectivity strongly decays after the writing process. A fortunate property here results from the recovery of the initial reflectivity using a post-inscription thermal annealing. Both behaviors are attributed to the evolution between trans- and cis-isomers. PMID- 27367069 TI - Measurement of Pockels' coefficients and demonstration of the anisotropy of the elasto-optic effect in optical fibers under axial strain. AB - The elasto-optic effect in optical fibers under axial strain can be characterized by means of the whispering gallery mode (WGM) resonances of the fiber itself. This technique enables a direct measurement of the anisotropy, the determination of the individual Pockels' coefficients, and the study of the wavelength dependence. The method is based on a rigorous theoretical study of WGM resonances in cylindrical microresonators. The shift of the WGM resonances as a function of strain was measured for the TE and TM modes, showing a strong modal anisotropy. In particular, the shift rate for TE modes was 1.84 times the one for TM modes. From these measurements, experimental values for the Pockels' coefficients were obtained: p11=0.116 and p12=0.255 at 1531 nm, and p11=0.131 and p12=0.267 at 1064 nm. The dispersion of p44 with wavelength was shown to be 5% MUm-1. PMID- 27367070 TI - Engineered second-harmonic diffraction from highly transmissive metasurfaces composed of complementary split-ring resonators. AB - We theoretically and experimentally investigated the optical second-harmonic (SH) diffraction from metasurfaces based on gold complementary split-ring resonators (CSRRs). We have demonstrated that the generated SH currents are mostly parallel to the incident polarization and are asymmetric with respect to the base of a CSRR, thus allowing us to impose the phase change of pi on the SH radiation by reversing the CSRR's orientation. We verified this concept of geometry-induced nonlinear phase by designing and fabricating a nonlinear metasurface consisting of supercells of CSRRs with opposite orientations that can function as a SH beam splitter. The ability to control the phase of the local nonlinearity coupled with the high transmittance at both fundamental and SHG wavelengths makes the CSRRs good candidates for the construction of highly efficient three-dimensional nonlinear metamaterials and suitable for applications in nonlinear beam shaping. PMID- 27367071 TI - Generation of nearly 3D-unpolarized evanescent optical near fields using total internal reflection. AB - We analyze the time-domain partial polarization of optical fields composed of two evanescent waves created in total internal reflection by random electromagnetic beams with orthogonal planes of incidence. We show that such a two-beam configuration enables to generate nearly unpolarized, genuine three-component (3D) near fields. This result complements earlier studies on spectral polarization, which state that at least three symmetrically propagating beams are required to produce a 3D-unpolarized near field. The degree of polarization of the near field can be controlled by adjusting the polarization states and mutual correlation of the incident beams. PMID- 27367072 TI - Real-time shot-noise-limited differential photodetection for atomic quantum control. AB - We demonstrate high-efficiency, shot-noise-limited differential photodetection with real-time signal conditioning, suitable for feedback-based quantum control of atomic systems. The detector system has quantum efficiency of 0.92, is shot noise-limited from 7.4*105 to 3.7*108 photons per pulse, and provides real-time voltage-encoded output at up to 2.3 M pulses per second. PMID- 27367073 TI - High-resolution low-frequency fluctuation map of a multimode laser diode subject to filtered optical feedback via a fiber Bragg grating. AB - A highly detailed and extended map of low-frequency fluctuations is established for a high-power multi-mode 980 nm laser diode subject to filtered optical feedback from a fiber Bragg grating. The low-frequency fluctuations limits and substructures exhibit substantial differences with previous works. PMID- 27367074 TI - Probing dipole-dipole interaction in a rubidium gas via double-quantum 2D spectroscopy. AB - We have implemented double-quantum 2D spectroscopy on a rubidium vapor and shown that this technique provides sensitive and background-free detection of the dipole-dipole interaction. The 2D spectra include signals from both individual atoms and interatomic interactions, allowing quantitative studies of the interaction. A theoretical model based on the optical Bloch equations is used to reproduce the experimental spectrum and confirm the origin of double-quantum signals. PMID- 27367075 TI - Photoinduction of spontaneous surface relief gratings on Azo DR1 glass. AB - Surface relief gratings were spontaneously photoinduced from a collimated Nd:YAG laser beam at 532 nm on thin films of a disperse red 1 functionalized glass forming compound. Pattern formation was studied by measuring the diffraction intensity of a He-Ne laser probe beam at 633 nm and by atomic force microscopy (AFM). The dependence of pattern formation on both irradiation time and intensity was studied. The gratings could be erased both optically and thermally. The orientation of the gratings is influenced by the polarization of the writing beam, and it is accompanied by strong diffraction of the incident light into the sample plane, thereby providing a way to couple and trap the light into the substrate. Interestingly, photobleaching upon prolonged irradiation yields transparent gratings, and the process is partially reversible upon thermal erasure. PMID- 27367076 TI - Fourier transform-limited optical frequency-modulated continuous-wave interferometry over several tens of laser coherence lengths. AB - We report on a versatile optical frequency-modulated continuous-wave interferometry technique that exploits wideband phase locking for generating highly coherent linear laser frequency chirps. This technique is based on an ultra-short delay-unbalanced interferometer, which leads to a large bandwidth, short lock time, and robust operation even in the absence of any isolation from environmental perturbations. In combination with a digital delay-matched phase error compensation, this permits the achievement of a range window about 60 times larger than the intrinsic laser coherence length with a 1.25 mm Fourier transform limited spatial resolution. The demonstrated configuration can be easily applied to virtually any semiconductor laser. PMID- 27367077 TI - Single-fiber tweezers applied for dye lasing in a fluid droplet. AB - We report on the first demonstration of a single-fiber optical tweezer that is utilized to stabilize and control the liquid droplet for dye lasing. In order to trap a liquid droplet with a diameter of 15-30 MUm, an annular core micro structured optical fiber is adopted. By using wavelength division multiplexing technology, we couple a trapping light source (980 nm) and a pumping light source (532 nm) into the annular core of the fiber to realize the trapping, controlling, and pumping of the oil droplet. We show that the laser emission spectrum tunes along the same size as the oil droplet. The lasing threshold of the oil droplet with the diameter of 24 MUm is 0.7 MUJ. The presented fiber-based optical manipulation of liquid droplet micro-lasers can be easily combined with the micro fluidic chip technology and also may extend the application of optical fiber tweezers for micro-droplet lasing technology in the biological field. PMID- 27367078 TI - Broadband pump-probe spectroscopy at 20-MHz modulation frequency. AB - We introduce an innovative high-sensitivity broadband pump-probe spectroscopy system, based on Fourier-transform detection, operating at 20-MHz modulation frequency. A common-mode interferometer employing birefringent wedges creates two phase-locked delayed replicas of the broadband probe pulse, interfering at a single photodetector. A single-channel lock-in amplifier demodulates the interferogram, whose Fourier transform provides the differential transmission spectrum. Our approach combines broad spectral coverage with high sensitivity, due to high-frequency modulation and detection. We demonstrate its performances by measuring two-dimensional differential transmission maps of a carbon nanotubes sample, simultaneously acquiring the signal over the entire 950-1350 nm range with 2.7.10-6 rms noise over 1.5 s integration time. PMID- 27367079 TI - Diode-based microbolometer with performance enhanced by broadband metamaterial absorber. AB - This Letter reports a microbolometer integrated with a broadband metamaterial absorber (MMA) to enhance its performance, which contains series-connected silicon diodes as the temperature sensor. The broadband MMA is readily integrated into the device by introducing an array of different-sized square resonators on the silicon nitride structural layer, while the widened titanium interconnecting wires between individual diodes serve as the ground plane. In a comparative experiment, the broadband MMA was demonstrated to be superior to the ordinary silicon nitride absorber in a broad spectra range, especially in a long wavelength IR regime, which directly leads to an increase in IR responsivity by 60%. More importantly, this enhancement in responsivity was achieved with no sacrifice of the response time due to the negligible thermal mass of the introduced resonator array. PMID- 27367080 TI - Plasmonic Zener tunneling in binary graphene sheet arrays. AB - We investigate the plasmonic Zener tunneling (ZT) in arrays of weakly coupled graphene sheet waveguides. By alternatively arranging the graphene waveguides with two different chemical potentials, the single surface plasmon polariton (SPP) band splits into two minibands, and tunneling between them occurs at the edge of the Brillouin zone. With a linear gradient of the propagation constant introduced by appropriately tuning the chemical potential distribution over the graphene sheet, the SPPs exhibit a sequence of Bloch oscillations and ZT transitions in the arrays. The simulated tunneling rate coincides with the theoretical analysis based on the coupled-mode theory, which can be tuned by varying the chemical potential difference between adjacent graphene. PMID- 27367081 TI - Doppler-free spectroscopy on the Cs D1 line with a dual-frequency laser. AB - We report on Doppler-free laser spectroscopy in a Cs vapor cell using a dual frequency laser system tuned on the Cs D1 line. Using counter propagating beams with crossed linear polarizations, an original sign reversal of the usual saturated absorption dip and large increase in Doppler-free atomic absorption is observed. This phenomenon is explained by coherent population trapping (CPT) effects. The impact of laser intensity and light polarization on absorption profiles is reported in both single-frequency and dual-frequency regimes. In the latter, frequency stabilization of two diode lasers was performed, yielding a beat note fractional frequency stability at the level of 3*10-12 at 1 s averaging time. These performances are about an order of magnitude better than those obtained using a conventional single-frequency saturated absorption scheme. PMID- 27367082 TI - Light sheet luminescence imaging with Cherenkov excitation in thick scattering media. AB - Light scattering leads to a severe loss of axial and transverse resolution with depth into tissue, limiting accuracy and value of biomedical luminescence imaging techniques. High-resolution imaging beyond a few-millimeter depth is prohibited because diffusive transport dominates beyond a few scattering distances. In this study, light sheet imaging through scattering media is demonstrated using a radiotherapy linear accelerator to deliver well-defined thin scanned sheets of x rays. These sheets produce Cherenkov light within the medium, which in turn excites luminescence of an optical probe across the sheet plane. This luminescence can then be imaged by an intensified camera positioned perpendicular to the sheet plane. The precise knowledge of the light sheet position within the medium allowed for efficient attenuation correction of the signal with depth as well as spatial deconvolution of the excitation light. Together these methods allowed for the first time, to the best of our knowledge, high-resolution imaging of tissue-equivalent phantoms up to 3 cm thick, yielding the precise position and shape of luminescent lesions located deep in tissue without the need for nonlinear image reconstruction. PMID- 27367083 TI - Injection-locked semiconductor laser-based frequency comb for modulation applications in RF analog photonics. AB - A linearized intensity modulator for periodic and pulsed light is proposed and demonstrated. The free carrier plasma effect has been used to modulate the refractive index of the phase section of a three-section mode-locked laser. If injection locked, the modulation induces an arcsine phase response on the three section mode-locked laser. By introducing this mode-locked laser into a Mach Zehnder interferometer biased at quadrature, one can realize a true linear intensity modulation. This novel laser suppresses any unwanted amplitude modulation and increases the performance of the linearized intensity modulator. Experimental results have provided a record low static Ipi of 0.39 mA and a spur-free dynamic range of 75 dB.Hz2/3. PMID- 27367084 TI - Dual-frequency injection-locked continuous-wave near-infrared laser. AB - We report a dual-frequency injection-locked continuous-wave near-infrared laser. The entire system consists of a Ti:sapphire ring laser as a power oscillator, two independent diode lasers employed as seed lasers, and a master cavity providing a frequency reference. Stable dual-frequency injection-locked oscillation is achieved with a maximum output power of 2.8 W. We show its single longitudinal/transverse mode characteristics and practical power stability, as fundamental performance features of this laser system. We also demonstrate arbitrary selectivity of the two frequencies and flexible control of their relative powers by simply manipulating the seed lasers, as advanced features. PMID- 27367085 TI - Terahertz time-domain electro-optic measurements by femtosecond laser pulses with an edge-cut spectrum. AB - Balanced electro-optic detection techniques of terahertz wave radiation are proposed based on variations of the energy and ellipticity of laser pulses with an edge-cut spectrum. The techniques are compared with the standard electro-optic detection scheme utilizing laser pulses with Gaussian spectrum shape. Our calculations and measurements show that the studied schemes have a much better response to the terahertz wave radiation at high frequencies compared with the standard one. PMID- 27367086 TI - Ultralow crosstalk nanosecond-scale nested 2 * 2 Mach-Zehnder silicon photonic switch. AB - We present the design and characterization of a novel electro-optic silicon photonic 2*2 nested Mach-Zehnder switch monolithically integrated with a CMOS driver and interface logic. The photonic device uses a variable optical attenuator in order to balance the power inside the Mach-Zehnder interferometer leading to ultralow crosstalk performance. We measured a crosstalk as low as 34.5 dB, while achieving ~2 dB insertion loss and 4 ns transient response. PMID- 27367087 TI - High contrast, 86 fs, 35 mJ pulses from a diode-pumped, Yb:glass, double chirped-pulse amplification laser system. AB - We demonstrate the generation of 86 fs, 35 mJ, high-contrast laser pulses at 1030 nm with a repetition rate of 1 Hz from a diode-pumped double chirped-pulse amplification setup. The pulses exhibit a spectral bandwidth exceeding 27 nm full width at half-maximum. This could be achieved by using a laser architecture comprising two stages of chirped pulse amplification with a cross-polarized wave generation filter in between, by applying spectral shaping and by increasing the spectral hard-clip of the second stretcher. These are, to the best of our knowledge, the shortest pulses at the mJ level with ultra-high contrast generated with a diode-pumped front end at 1030 nm. PMID- 27367088 TI - Extreme events and crises observed in an all-solid-state laser with modulation of losses. AB - We report observations of extreme events (or dissipative optical rogue waves) in a laser with a modulated parameter (cavity losses). Experimental data supporting the hypothesis that these events are related with multi-stability and external crises is presented. It is also shown that the time separation between a pulse and an extreme event can be predicted more accurately than that between pulses of average intensity, in agreement with the theoretical description and opening the road to the prediction and control of extreme optical events. PMID- 27367089 TI - Broadband fiber-chip zero-order surface grating coupler with 0.4 dB efficiency. AB - Surface grating couplers enable efficient coupling of light between optical fibers and nanophotonic waveguides. However, in conventional grating couplers, the radiation angle is intrinsically wavelength dependent, thereby limiting their operation bandwidth. In this Letter, we present a zero-order surface grating coupler in silicon-on-insulator which overcomes this limitation by operating in the subwavelength regime. By engineering the effective refractive index of the grating region, both high coupling efficiency and broadband operation bandwidth are achieved. The grating is assisted by a silicon prism on top of the waveguide, which favors upward radiation and minimizes power losses to substrate. Using a linear apodization, our design achieves a coupling efficiency of 91% (-0.41 dB) and a 1-dB bandwidth of 126 nm. PMID- 27367090 TI - High peak and average power Ti:sapphire thin disk amplifier with extraction during pumping. AB - The combination of the extraction during pumping (EDP) amplification scheme and the thin disk (TD) technology has been successfully applied to the Ti:sapphire (Ti:sa) laser medium for the first time, to the best of our knowledge. In a proof of-principle experiment, we demonstrate high energy broadband amplification in a room temperature water cooled EDP-TD head of stretched femtosecond pulses at a 10 Hz repetition rate, instead of performing a cryogenically cooled traditional multi-pass scheme. Hence, the EDP-TD combination can overcome the limits associated with thermal effects and transverse amplified spontaneous emission, enabling Ti:sa laser systems to have a petawatt peak and hundreds of watts of average power. PMID- 27367091 TI - Broadband stimulated Raman microscopy with 0.1 ms pixel acquisition time. AB - Femtosecond stimulated Raman microscopy (FSRM) is a nonlinear technique for rapid broadband Raman imaging. It utilizes a few femtosecond probe pulse and a narrow bandwidth pump pulse. Using a fast (20 kHz) multi-channel detector, stimulated Raman spectra can be recorded with an acquisition time as short as 0.1 ms. In this Letter, spectra of neat benzonitrile at different acquisition speeds are presented to benchmark the FSRM setup. Furthermore, chemical maps of a multi phase polymer blend are recorded using the fastest acquisition rate possible with the current instrument. PMID- 27367092 TI - Hollow-core fiber Fabry-Perot photothermal gas sensor. AB - A highly sensitive, compact, and low-cost trace gas sensor based on photothermal effect in a hollow-core fiber Fabry-Perot interferometer (FPI) is described. The Fabry-Perot sensor is fabricated by splicing a piece of hollow-core photonic bandgap fiber (HC-PBF) to single-mode fiber pigtails at both ends. The absorption of a pump beam in the hollow core results in phase modulation of probe beam, which is detected by the FPI. Experiments with a 2 cm long HC-PBF with femtosecond laser drilled side-holes demonstrated a response time of less than 19 s and noise equivalent concentration (NEC) of 440 parts-per-billion (ppb) using a 1 s lock-in time constant, and the NEC goes down to 117 ppb (2.7*10-7 in absorbance) by using 77 s averaging time. PMID- 27367093 TI - Ultra-compact on-chip LED collimation optics by 3D femtosecond direct laser writing. AB - By using two-photon lithographic 3D printing, we demonstrate additive manufacturing of a dielectric concentrator directly on a LED chip. With a size of below 200 MUm in diameter and length, light output is increased by a factor of 6.2 in collimation direction, while the emission half-angle is reduced by 50%. We measure excellent form fidelity and irradiance patterns close to simulation. Additionally, a more complex shape design is presented, which exhibits a nonconventional triangular illumination pattern. The introduced method features exceptional design freedoms which can be used to tailor high-quality miniature illumination optics for specific lighting tasks, for example, endoscopy. PMID- 27367094 TI - Yb-fiber laser pumped high-power, broadly tunable, single-frequency red source based on a singly resonant optical parametric oscillator. AB - We present an efficient and tunable source generating multi-watt single-frequency red radiation by intra-cavity frequency doubling of the signal in a MgO-doped periodically poled LiNbO3 (MgO:PPLN)-based singly resonant optical parametric oscillator (SRO). By optimally designing the SRO cavity in a six mirror configuration, we generate ~276 nm tunable idler radiation in mid infrared with a maximum power of Pi=2.05 W at a pump power of Pp=14.0 W. The resonant signal is frequency doubled using a 10 mm long BiB3O6 (BiBO) crystal which resulted in tunability of a red beam from ~753 to 780 nm band with maximum power Pr~4.0 W recorded at lambdar~756 nm. The deployment of a six-mirror SRO ensures single-frequency generation of red across the entire tuning range by inducing additional losses to Raman modes of LiNbO3 and, thus, inhibiting their oscillation. Using a scanning Fabry-Perot interferometer (FPI), nominal linewidth of the red beam is measured to ~3 MHz which changes marginally over the entire tuning range. Long-term (over 1 h) peak-to-peak frequency fluctuation of the generated red beam is estimated to be about 3.3 GHz under free running conditions at Pp=14.0 W. The generated red beam is delivered in a TEM00 mode profile with M2<=1.32 at maximum power in a red beam. PMID- 27367095 TI - Differential interference contrast tomography. AB - We present a new approach to optical tomography of phase objects that is referred to as differential interference contrast tomography (DICT). The main feature of DICT is that the result of tomographic reconstruction is a 3D DIC image. This image is described by partial derivative of 3D refractive index distribution in one direction. The DICT setup consists of a lateral shearing phase-shifting interference microscope with low-coherent LED illumination. To create projections of the sample at various illumination angles, an angular scanning beam was used. 3D DIC tomograms of a white blood cell are presented. The comparison between the reconstructed DIC tomogram slices and the conventional DIC images of the same sample at the same depths are also represented. PMID- 27367096 TI - Broadband 2 * 2 adiabatic 3 dB coupler using silicon-on-insulator sub-wavelength grating waveguides. AB - We report on a compact, broadband, 2*2 adiabatic 3 dB coupler using sub wavelength gratings (SWGs) for silicon-on-insulator waveguides. In our device, two SWG waveguides that support two transverse electric modes and have tapered waveguide widths were used to achieve an adiabatic mode evolution of the two waveguide system for broadband 3 dB power splitting. We present results for a SWG adiabatic 3 dB coupler that has an overall coupler length of 50 MUm and achieves broadband power splitting over a 130 nm wavelength range with an imbalance of no greater than +/-0.3 dB and with low excess losses of less than 0.5 dB. PMID- 27367097 TI - Development of a hybrid Raman spectroscopy and optical coherence tomography technique for real-time in vivo tissue measurements. AB - We report on the development of a unique sideview handheld hybrid Raman spectroscopy (RS) and optical coherence tomography (OCT) technique for real-time in vivo tissue measurements. A sideview handheld RS-OCT optical probe is designed to coalign the optical paths of RS and OCT sampling arms, whereby a compact long pass dichroic mirror (LPDM) is utilized to transmit the OCT signal through a gradient index rod lens and a reflection mirror, whereas the LPDM deflects the tissue Raman signal by 90 degrees , leading to coaligned RS/OCT optical samplings on the tissue. Further study shows that the hybrid RS and OCT technique developed is capable of simultaneously acquiring both morphological and biochemical information about the oral tissue in vivo, facilitating real-time, in vivo tissue diagnoses and characterizations in the oral cavity. PMID- 27367098 TI - Dark-state lasers: mode management using exceptional points. AB - By exploiting the inherent characteristics of dark-state resonators, we experimentally realize a single-frequency integrated microring laser system. This semiconductor laser can remain single-mode, even at high pump power levels, while allowing tunability over a wide spectral range. Our results demonstrate the potential of exceptional points as a versatile tool for mode selection in micro cavity laser configurations. PMID- 27367099 TI - Gamma radiation effects on silicon photonic waveguides. AB - To support the use of integrated photonics in harsh environments, such as outer space, the hardness threshold to high-energy radiation must be established. Here, we investigate the effects of gamma (gamma) rays, with energy in the MeV-range, on silicon photonic waveguides. By irradiation of high-quality factor amorphous silicon core resonators, we measure the impact of gamma rays on the materials incorporated in our waveguide system, namely amorphous silicon, silicon dioxide, and polymer. While we show the robustness of amorphous silicon and silicon dioxide up to an absorbed dose of 15 Mrad, more than 100* higher than previous reports on crystalline silicon, polymer materials exhibit changes with doses as low as 1 Mrad. PMID- 27367100 TI - Wide-field broadband extreme ultraviolet transmission ptychography using a high harmonic source: publisher's note. AB - This note amends the list of funders in a recent Letter [Opt. Lett.41, 1317 (2016)OPLEDP0146-959210.1364/OL.41.001317]. PMID- 27367101 TI - Design and fabrication of elliptical-core few-mode fiber for MIMO-less data transmission. AB - We propose a design strategy of elliptical core few-mode fiber (e-FMF) that supports three spatial modes with enhanced mode spacing between LP11a and LP11b, to suppress intra-mode coupling during mode-division multiplexing (MDM) transmission. Our theoretical investigations show that there exist two optimization regimes for the e-FMF, as a comparison with traditional circular core FMF(c-FMF). At the regime of three-mode operation, there occurs a trade-off between mode spacing and bending-induced loss. Meanwhile, in terms of five-mode regime, a trade-off between mode spacing and high-order mode crosstalk happens. Finally, we fabricate 7.94 km e-FMF with the optimal parameters, based on the commercial fiber manufacture facility. The primary characterizations at 1550 nm show that three spatial modes of e-FMF can be transmitted with a loss less than 0.3 dB/km. Meanwhile, -22.44 dB crosstalk between LP11a and LP11b is observed, even when the 2 km e-FMF is under stress-induced strong perturbation. PMID- 27367102 TI - Resonant optical propulsion of a particle inside a hollow-core photonic crystal fiber. AB - Resonant propulsion of small nonresonant particles inside metal waveguides due to the formation of resonant states by the guided modes below their cutoffs has been predicted in the past. Here it is shown that stable resonant propulsion exists in hollow-core photonic crystal fibers, which are all-dielectric structures and are a major platform for various photonic applications. Specific features of the resonant propulsion are discussed together with the fiber design issues. The results may enable power-efficient transport of particles over long distances, particle sorting, and sensitive detection. PMID- 27367103 TI - Algebraic invariants for reflection Mueller polarimetry via uncompensated double pass illumination-collection optics. AB - We report on the identification of the two algebraic invariants inherent to Mueller matrix polarimetry measurements performed through double pass illumination-collection optics (e.g., an optical fiber or an objective) of unknown polarimetric response. The practical use of the invariants, potentially applicable to the characterization of nonreciprocal media, is illustrated on experimental examples. PMID- 27367104 TI - Coriolis effect and spin Hall effect of light in an inhomogeneous chiral medium. AB - We theoretically investigate the spin Hall effect of spinning light in an inhomogeneous chiral medium. The Hamiltonian equations of the photon are analytically obtained within eikonal approximation in the noninertial orthogonal frame. Besides the usual spin curvature coupling, the chiral parameter enters the Hamiltonian as a spin-torsion-like interaction. We reveal that both terms have parallel geometric origins as the Coriolis terms of Maxwell's equations in nontrivial frames. PMID- 27367105 TI - Femtosecond laser direct inscription of surface skimming waveguides in bulk glass. AB - We present a detailed study of waveguide inscription near the surface of bulk glass using a femtosecond laser. Three silicate glasses used extensively as hosts for photo-induced photonic devices were examined. Our results show that near surface waveguides generally present a low-index contrast, as the pulse energy damage threshold decreases sharply at close proximity to the surface. We devised a novel method to allow the formation of optical waveguides that exhibit a high index contrast up to the surface of any transparent material. As a proof of concept, the inscription of near-surface single-mode waveguides operating at a wavelength of 405 nm is demonstrated. PMID- 27367106 TI - Calibration-free imaging through a multicore fiber using speckle scanning microscopy. AB - The images produced by multicore endoscopes are pixelated, and their resolution is limited by the core-to-core spacing. Lenses can be used to improve the resolution, but this reduces the field of view proportionally. Lensless endoscopy through multicore fibers can be achieved by using wavefront shaping techniques. This requires a calibration step, and the conformation of the fiber must remain constant over time. Here we demonstrate that, without a calibration step and in the presence of core-to-core coupling, we can obtain fluorescence images with a resolution better than the core-to-core spacing. This is accomplished by taking advantage of the memory effect present in these kinds of fibers. PMID- 27367107 TI - Wavelength-switched phase interrogator for extrinsic Fabry-Perot interferometric sensors. AB - We report on phase interrogation of extrinsic Fabry-Perot interferometric (EFPI) sensors through a wavelength-switched unit with a polarization-maintaining fiber Bragg grating (PMFBG). The measurements at two wavelengths are first achieved in one total-optical path. The reflected peaks of the PMFBG with two natural wavelengths are in mutually perpendicular polarization detection, and they are switched through an electro-optic modulator at a high switching speed of 10 kHz. An ellipse fitting differential cross multiplication (EF-DCM) algorithm is proposed for interrogating the variation of the gap length of the EFPI sensors. The phase demodulation system has been demonstrated to recover a minimum phase of 0.42 MUrad/Hz at the test frequency of 100 Hz with a stable intensity fluctuation level of +/-0.8 dB. Three EFPI sensors with different cavity lengths are tested at the test frequency of 200 Hz, and the results indicate that the system can achieve the demodulation of EFPI sensors with different cavity lengths stably. PMID- 27367108 TI - Encoding information using Laguerre Gaussian modes over free space turbulence media. AB - We experimentally demonstrate an efficient information transmission technique using Laguerre Gaussian (LG) modes. This technique is based on multiplexing and demultiplexing multiple LG modes with different azimuthal and radial components. At the reception, the initially sent modes encoding the information are extracted with high fidelity using a complete decomposition allowing to identify a particular mode from a set of modes within a unique iteration. Importantly, we investigate the effects of the atmospheric turbulence on the proposed communication system. We believe that the proposed technique is promising for high-bit-rate spatial division multiplexing in optical fiber and free space communication systems. PMID- 27367109 TI - Low-loss photonic device in Ge-Sb-S chalcogenide glass. AB - Low-loss waveguides constitute an important building block for integrated photonic systems. In this work, we investigated low-loss photonic device fabrication in Ge23Sb7S70 chalcogenide glass using electron beam lithography followed by plasma dry etching. High-index contrast waveguides with a low propagation loss of 0.5 dB/cm and microdisk resonators with an intrinsic quality factor (Q-factor) of 1.2*106 were demonstrated. Both figures represent, to the best of our knowledge, the best low loss results reported thus far in submicrometer single-mode chalcogenide glass devices. PMID- 27367110 TI - Modulation of optical spatial coherence by surface plasmon polaritons. AB - The interference pattern observed in Young's double-slit experiment is intimately related to the statistical correlations of the waves emitted by the slits. As the waves in the slits become more correlated, the visibility of the interference pattern increases. Here, we experimentally modulate the statistical correlations between the optical fields emitted by a pair of slits in a metal film. The interaction between the slits is mediated by surface plasmon polaritons and can be tuned by the slit separation, which allows us to either increase or decrease the spatial coherence of the emerging fields relative to that of the incoming fields. PMID- 27367111 TI - Uniqueness in multispectral constant-wave epi-illumination imaging. AB - Multispectral tissue imaging based on optical cameras and continuous-wave tissue illumination is commonly used in medicine and biology. Surprisingly, there is a characteristic absence of a critical look at the quantities that can be uniquely characterized from optically diffuse matter by multispectral imaging. Here, we investigate the fundamental question of uniqueness in epi-illumination measurements from turbid media obtained at multiple wavelengths. By utilizing an analytical model, tissue-mimicking phantoms, and an in vivo imaging experiment we show that independent of the bands employed, spectral measurements cannot uniquely retrieve absorption and scattering coefficients. We also establish that it is, nevertheless, possible to uniquely quantify oxygen saturation and the Mie scattering power-a previously undocumented uniqueness condition. PMID- 27367112 TI - All-optical modulation in wavelength-sized epsilon-near-zero media. AB - We investigate the interaction of two pulses (pump and probe) scattered by a nonlinear epsilon-near-zero (ENZ) slab whose thickness is comparable with the ENZ wavelength. We show that when the probe has a narrow spectrum localized around the ENZ wavelength, its transmission is dramatically affected by the intensity of the pump. Conversely, if the probe is not in the ENZ regime, its propagation is not noticeably affected by the pump. Such all-optical modulation is due to the oversensitive character of the ENZ regime, and it is so efficient that it even occurs in a wavelength thick slab. PMID- 27367113 TI - Divided-pulse amplification to the joule level. AB - Divided-pulse amplification (DPA) has proven to be a valuable tool in scaling the peak power of diode-pumped ytterbium-doped amplifiers to beyond the single-pulse threshold for parasitic nonlinear effects. DPA enables the amplification of picosecond pulses in solid-state amplifiers with limited bandwidth beyond the single-pulse damage threshold. In this Letter, we demonstrate DPA of picosecond pulses in a flashlamp-pumped Nd:YAG amplifier for the first time, to the best of our knowledge, yielding a combined pulse energy of 167 mJ. PMID- 27367114 TI - Effect of loss on slow-light-enhanced second-harmonic generation in periodic nanostructures. AB - We theoretically analyze the dependence of second-harmonic generation efficiency on the group index in periodic optical waveguides with loss. We investigate different possible scenarios of using slow light to enhance the efficiency of this process and show that in some cases there exists a maximally achievable efficiency reached for finite values of the group index at the point of phase matching. Furthermore, we identify situations for which slow light, surprisingly, does not enhance the second-harmonic generation efficiency. Our results are corroborated by rigorous nonlinear simulations of second-harmonic generation in periodic nanobeam waveguides with loss. PMID- 27367115 TI - Catastrophe optics of sharp-edge diffraction. AB - A classical problem of diffraction theory, namely plane wave diffraction by sharp edge apertures, is here reformulated from the viewpoint of the fairly new subject of catastrophe optics. On using purely geometrical arguments, properly embedded into a wave optics context, uniform analytical estimates of the diffracted wavefield at points close to fold caustics are obtained, within paraxial approximation, in terms of the Airy function and its first derivative. Diffraction from parabolic apertures is proposed to test reliability and accuracy of our theoretical predictions. PMID- 27367116 TI - Synthesis of arbitrary pulse waveforms in QCL-seeded ns-pulse CO2 laser for optimization of an LPP EUV source. AB - One of the unique features of the quantum-cascade-laser-seeded, nanosecond-pulse CO2 laser, invented for the purpose of generation of extreme UV by laser-produced-plasma, is a robust synthesis of arbitrary pulse waveforms. In the present Letter we report on experimental results that are, to our best knowledge, the first demonstration of such functionality obtainable from nanosecond-pulse CO2 laser technology. An online pulse duration adjustment within 10-40 ns was demonstrated, and a few exemplary pulse waveforms were synthesized, such as "tophat," "tailspike," and "leadspike" shapes. Such output characteristics may be useful to optimize the performance of LPP EUV source. PMID- 27367117 TI - Excellent color rendering index and high quantum efficiency of rare-earth-free fluosilicate glass for single-phase white light phosphor. AB - A rare-earth-free Sn-doped fluosilicate (SF) glass for single-phase white light phosphor has been investigated, which has a high color rendering index (98.3) and a quantum efficiency (85%). Moreover, by combining with a 280 nm LED chip directly, the Commission Internationale de l'Eclairage (CIE) coordinate (x=0.32, y=0.33) and correlated color temperature (5620 K) are close to the standard white light illumination. SF glass is a promising candidate as an alternative single phase white light phosphor for use in general lighting devices. PMID- 27367118 TI - Non-Markovianity induced by a single-photon wave packet in a one-dimensional waveguide. AB - The concept of non-Markovianity (NM) in quantum dynamics is still an open debate. Understanding how to generate and measure NM in specific models may aid in this quest. In quantum optics, an engineered electromagnetic environment coupled to a single atom can induce NM. The most common scenario of structured electromagnetic environment is an optical cavity, composed by a pair of mirrors. Here, we show how to generate and measure NM on a two-level system coupled to a one-dimensional waveguide with no mirrors required. The origin of the non-Markovian behavior lies in the initial state of the field, prepared as a single-photon packet. NM is shown to depend on two experimentally controllable parameters, namely, the linewidth of the packet and its central frequency. We relate the presence of NM to quantum interference. We also show how the two output channels of the waveguide provide distinct signatures of NM, both experimentally accessible. PMID- 27367119 TI - Mode converters based on cascaded long-period waveguide gratings. AB - We propose a mode-conversion platform based on cascaded long-period waveguide gratings. We demonstrate two specific devices by cascading a surface-corrugated grating and a sidewall-corrugated grating. One device allows conversion among the LP01, LP11b, and LP11a modes in a cyclic manner. The maximum conversion efficiency of a typical experimental device fabricated with polymer materials is about 94% at 1540 nm. The other device allows conversion between the LP01 and LP21a modes. The maximum conversion efficiency of a typical experimental device is estimated to be higher than 90% at 1550 nm. The performance of both devices is polarization-insensitive. The proposed platform could be developed into various mode converters for mode division-multiplexing systems and other mode-sensitive applications. PMID- 27367120 TI - Frequency-comb-assisted broadband precision spectroscopy with cascaded diode lasers. AB - Frequency-comb-assisted diode laser spectroscopy, employing both the accuracy of an optical frequency comb and the broad wavelength tuning range of a tunable diode laser, has been widely used in many applications. In this Letter, we present a novel method using cascaded frequency agile diode lasers, which allows us to extend the measurement bandwidth to 37.4 THz (1355-1630 nm) at megahertz resolution with scanning speeds above 1 THz/s. It is demonstrated as a useful tool to characterize a broadband spectrum for molecular spectroscopy, and in particular it enables us to characterize the dispersion of integrated microresonators up to the 4th-order. PMID- 27367121 TI - 2 * 2 multiple-input multiple-output optical-wireless integration system based on optical independent-sideband modulation enabled by an in-phase/quadrature modulator. AB - We propose a novel and simple 2*2 multiple-input multiple-output (MIMO) optical wireless integration system, in which optical independent-sideband modulation enabled by an in-phase/quadrature (I/Q) modulator, instead of optical polarization multiplexing, is used to assist the simultaneous generation of two wireless millimeter-wave (mm-wave) signals. Software-based digital signal processing is used to generate the driving signal for the I/Q modulator, the output of which is two independent single-sideband optical vector signals located at two sides of a large central optical carrier. Based on our proposed 2*2 MIMO optical-wireless integration system, we experimentally demonstrate the simultaneous generation and 2*2 MIMO wireless delivery of two independent 40-GHz quadrature-phase-shift-keying (QPSK) wireless mm-wave signals. Each 40-GHz QPSK wireless mm-wave signal can carry up to 4-Gbaud transmitter data with a bit-error ratio less than the hard-decision forward-error-correction threshold of 3.8*10-3. PMID- 27367123 TI - Tunable surface plasmon wave plates. AB - The highest resonant transmission through an array of holes perforated in metallic screens occurs when the dielectric constant of the substrate, the superstrate, and the hole are the same. Changes in the refractive index of the homogenous environment also produce the largest shift in resonances per refractive index unit. In this Letter, we first propose and apply a technique in realization of a freestanding bi-periodic array of holes perforated in a silver film. We then show both numerically and experimentally that shifts in (1,0) and (0,1) modes in response to changes in the refractive index of the surrounding dielectric provide a mechanism for realization of a miniaturized tunable quarter wave plate that operates in an extraordinary optical transmission mode with a high throughput and a near unity state of circularly polarized light. PMID- 27367122 TI - Tunable dual-band asymmetric transmission for circularly polarized waves with graphene planar chiral metasurfaces. AB - The asymmetric transmission effect has attracted great interest due to its wide modern optical applications. In this Letter, we present the underlying theory, the design specifications, and the simulated demonstration of tunable dual-band asymmetric transmission for circularly polarized waves with a graphene planar chiral metasurface. The spectral position of the asymmetric peak is linearly dependent on the Fermi energy and can be controlled by changing the Fermi energy. The success of tunable dual-band asymmetric transmission can be attributed to the enantiomerically sensitive plasmonic excitations of the graphene metasurface. This work offers a further step in developing tunable asymmetric transmission of circularly polarized waves for applications in detectors and other polarization sensitive electromagnetic devices. PMID- 27367124 TI - Hetero-core III-V/Si microlaser. AB - We design and demonstrate optically pumped microlasers with a hetero-core cavity formed by III-V and silicon-on-insulator (SOI) materials. Hetero-core cavities with identical lateral dimension are fabricated. The cavity is formed by III-V layer with thickness of 210 nm on top of SOI layer with thickness of 300 nm via SiO2 interlayer wafer bonding. Continuous wave laser operation is achieved for a diameter down to 2 MUm with a corresponding mode volume of 0.07lambda3 and quality factor of 1.3*104. The architecture renders an alternative laser structure for heterogeneous laser-on-chip, with no dedicated vertical coupling mechanism needed between the two materials' layers. PMID- 27367125 TI - Community pharmacist knowledge, attitudes and confidence regarding naloxone for overdose reversal. AB - AIM: Given the potential to expand naloxone supply through community pharmacy, the aim of this study was to estimate Australian pharmacists': (1) level of support for overdose prevention, (2) barriers and facilitators for naloxone supply and (3) knowledge about naloxone administration. DESIGN: Online survey from nationally representative sample of community pharmacies. SETTING: Australia, September-November 2015. PARTICIPANTS: A total of 1317 community pharmacists were invited to participate with 595 responses (45.1%). MEASUREMENTS: We assessed attitudes towards harm reduction, support for overdose prevention, attitudes and knowledge about naloxone. We tested the association between attitudes towards harm reduction and different aspects of naloxone supply. FINDINGS: Pharmacists were willing to receive training about naloxone (n = 479, 80.5%) and provide naloxone with a prescription (n = 537, 90.3%). Fewer (n = 234, 40.8%) were willing to supply naloxone over-the-counter. Positive attitudes towards harm reduction were associated with greater willingness to supply naloxone with a prescription [odds ratio (OR) = 1.15, 95% confidence interval (CI) = 1.11-1.19] and over-the-counter (OR = 1.13, 95% CI = 1.09-1.17). Few pharmacists were confident they could identify appropriate patients (n = 203, 34.1%) and educate them on overdose and naloxone use (n = 190, 31.9%). Mean naloxone knowledge scores were 1.8 (standard deviation 1.7) out of 5. More than half the sample identified lack of time, training, knowledge and reimbursement as potential barriers for naloxone provision. CONCLUSION: Community pharmacists in Australia appear to be willing to supply naloxone. Low levels of knowledge about naloxone pharmacology and administration highlight the importance of training pharmacists about overdose prevention. PMID- 27367126 TI - Scleral-flap Everting Suture. PMID- 27367127 TI - The Flap Lift Suture. PMID- 27367128 TI - Evaluation of the Macular Choroidal Thickness Using Spectral Optical Coherence Tomography in Pseudoexfoliation Glaucoma. PMID- 27367129 TI - Excision of the Tenon Capsule in Pediatric Trabeculectomy: A Controlled Study. PMID- 27367130 TI - Evaluation of Corneal Biomechanical Properties in Patients With Thyroid Eye Disease Using An Ocular Response Analyzer. PMID- 27367131 TI - The Origin of the Term Glaucoma: Owls or Light-colored Eyes? PMID- 27367132 TI - A Comment on the "Progression of Normal-tension Glaucoma After Ventriculoperitoneal Shunt to Decrease Cerebrospinal Fluid Pressure". J Glaucoma. 2016;25: e50-e52. PMID- 27367133 TI - Fiberoptic Microcatheter-assisted 360-Degree Trabeculotomy Ab Externo After Unsuccessful Trabeculotome Trabeculotomy in Primary Congenital Glaucoma: A Case Report. AB - Fiberoptic microcatheter-assisted 360-degree trabeculotomy ab externo is a recent technique. Retrospective studies have proved the effectiveness as a first-angle surgery in eyes with primary congenital glaucoma. However, there are no reports in which it is performed after another unsuccessful surgical procedure. We present our case of a monolateral congenital glaucoma. We first performed an ab externo trabeculotomy with poor control of intraocular pressure (IOP). Then, a microcatheter-assisted 360-degree trabeculotomy was performed with IOP lowering. Microcatheter-assisted 360-degree trabeculotomy supplies successful IOP lowering after another angle surgery procedure. PMID- 27367134 TI - Detectability of Visual Field Defects in Glaucoma With High-resolution Perimetry. AB - PURPOSE: To extrapolate the optimal test point resolution for assessment of glaucomatous visual field (VF) defects including subtle functional defects, we performed high-resolution perimetry with the 0.5 degrees test point resolution. SUBJECTS AND METHODS: Subjects were 11 eyes of 11 normal volunteers and 16 eyes of 16 glaucomatous patients. Octopus 900 custom test was used to measure 61 points with the test point resolution of 0.5 degrees on the temporal meridian of 45 degrees within the eccentricity of 30 degrees. In the glaucoma cases, VF profiles were extracted in 17 patterns of the test point resolutions that ranged from 0.5 to 8.5 degrees and the mean defect (MD), square root of loss variance (sLV), and maximum sensitivity loss (Max loss) were calculated. The influence of the test point resolution on MD, sLV, and Max loss was examined. In addition, the test range from the fixation point to the eccentricity of 30 degrees was divided into 3 zones. Similarly, each zone was investigated if the test point resolution exerted influence on the MD, sLV, and Max loss. RESULTS: Our glaucoma cases did not show any significant differences in MD and sLV regardless of the resolution. Max loss showed significant difference at resolution >=1.0 degree. MD and sLV did not show significant differences by the change of resolution in each zone. Max loss showed significant differences at resolution >=1.5 degrees within the central 10 degrees. CONCLUSIONS: To detect subtle VF defects within the eccentricity of 10 degrees, high-resolution perimetry with the test point resolution of <1.5 degrees is necessary. PMID- 27367135 TI - Intraocular Pressure During Robotic-assisted Laparoscopic Procedures Utilizing Steep Trendelenburg Positioning. PMID- 27367136 TI - Corneal Haze as Prognostic Indicator of Intraocular Pressure in Primary Congenital Glaucoma. AB - PURPOSE: To perform a longitudinal analysis on the association of corneal haze with intraocular pressure (IOP) in eyes with primary congenital glaucoma (PCG) over 3 years. PATIENTS AND METHODS: Charts of all patients diagnosed with glaucoma of childhood from 2002 to 2012 at our institution were retrospectively reviewed. Inclusion criteria were age 18 years and below, plus elevated IOP or characteristic clinical signs. Exclusion criteria were eyes with secondary glaucoma or corneal haze not from PCG and patients with prior ocular surgery or incomplete follow-up. RESULTS: Of 79 eyes with childhood glaucoma during this period, 36 eyes had PCG [25 patients; 15 male (60.0%), 14 bilateral (56.0%)]. Eighteen eyes (13 patients) presented with corneal haze, whereas 18 eyes (12 patients) did not. Eyes with haze were diagnosed at a younger age than eyes without haze (0.79 vs. 5.2 y, P<0.02). During year 1, eyes with haze underwent significantly more IOP-lowering procedures and used significantly fewer IOP lowering medications. Multivariate analysis revealed that corneal haze increased IOP by 4.63 mm Hg when controlling for treatment over time (P<0.01). Eyes with haze had lower survival curves and a failure hazard of 1.3 times that of eyes without haze. These eyes had a lower proportion of qualified successes than eyes without haze at year 1 (P<0.05) but this was reversed at year 3 (P<0.02). CONCLUSIONS: Eyes with PCG-related corneal haze generally presented more severely than did those without haze, but postmanagement outcomes may be similar to those in eyes without haze. PMID- 27367137 TI - Modified Scleral Tunnel to Prevent Tube Exposure in Patients With Refractory Glaucoma. AB - PURPOSE: To present and evaluate modified scleral tunnel in prevention of tube exposure following Ahmed valve implantation in refractory glaucoma. METHODS: In the Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, a retrospective study was conducted in 36 eyes of 34 patients who were diagnosed with refractory glaucoma and underwent Ahmed glaucoma valve implantation. In the surgery, the modified scleral tunnel was done to prevent tube exposure. RESULTS: At the end of follow-up (mean 21.68+/-9.25 mo), there was no conjunctival tube exposure in all 36 eyes. The mean intraocular pressure was 18.3+/-6.79 mmHg, and 8 eyes needed 1 to 3 types of drugs to decrease intraocular pressure. CONCLUSIONS: The modified scleral tunnel technique in Ahmed glaucoma valve implantation is able to prevent conjunctival tube exposure in the patients with refractory glaucoma. PMID- 27367138 TI - Localized, gradient-reversed ultrafast z-spectroscopy in vivo at 7T. AB - PURPOSE: To collect ultrafast z-spectra in vivo in situations where voxel homogeneity cannot be assured. THEORY: Saturating in the presence of a gradient encodes the frequency offset spatially across a voxel. This encoding can be resolved by applying a similar gradient during readout. Acquiring additional scans with the gradient polarity reversed effectively mirrors the spatial locations of the frequency offsets so that the same physical location of a positive offset in the original scan will contribute a negative offset in the gradient-reversed scan. METHODS: Gradient-reversed ultrafast z-spectroscopy (GRUFZS) was implemented and tested in a modified, localized PRESS sequence at 7T. Lysine phantoms were scanned at various concentrations and compared with coventionally-acquired z-spectra. Scans were acquired in vivo in human brain from homogeneous and inhomogeneous voxels with the ultrafast direction cycled between read, phase, and slice. Results were compared to those from a similar conventional z-spectroscopy PRESS-based sequence. RESULTS: Asymmetry spectra from GRUFZS are more consistent and reliable than those without gradient reversal and are comparable to those from conventional z-spectroscopy. GRUFZS offers significant acceleration in data acquisition compared to traditional chemical exchange saturation transfer methods with high spectral resolution and showed higher relative SNR effficiency. CONCLUSION: GRUFZS offers a method of collecting ultrafast z-spectra in voxels with the inhomogeneity often found in vivo. Magn Reson Med 76:1039-1046, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27367139 TI - Understanding Innovation Engines: Automated Creativity and Improved Stochastic Optimization via Deep Learning. AB - The Achilles Heel of stochastic optimization algorithms is getting trapped on local optima. Novelty Search mitigates this problem by encouraging exploration in all interesting directions by replacing the performance objective with a reward for novel behaviors. This reward for novel behaviors has traditionally required a human-crafted, behavioral distance function. While Novelty Search is a major conceptual breakthrough and outperforms traditional stochastic optimization on certain problems, it is not clear how to apply it to challenging, high dimensional problems where specifying a useful behavioral distance function is difficult. For example, in the space of images, how do you encourage novelty to produce hawks and heroes instead of endless pixel static? Here we propose a new algorithm, the Innovation Engine, that builds on Novelty Search by replacing the human-crafted behavioral distance with a Deep Neural Network (DNN) that can recognize interesting differences between phenotypes. The key insight is that DNNs can recognize similarities and differences between phenotypes at an abstract level, wherein novelty means interesting novelty. For example, a DNN-based novelty search in the image space does not explore in the low-level pixel space, but instead creates a pressure to create new types of images (e.g., churches, mosques, obelisks, etc.). Here, we describe the long-term vision for the Innovation Engine algorithm, which involves many technical challenges that remain to be solved. We then implement a simplified version of the algorithm that enables us to explore some of the algorithm's key motivations. Our initial results, in the domain of images, suggest that Innovation Engines could ultimately automate the production of endless streams of interesting solutions in any domain: for example, producing intelligent software, robot controllers, optimized physical components, and art. PMID- 27367140 TI - Hospital Social Work and Spirituality: Views of Medical Social Workers. AB - This article is based on a study of 1,389 medical social workers in 108 hospitals across 12 countries, on their views on spirituality and spiritually sensitive interventions in hospital settings. Results of the logistic regression analyses and structural equation models showed that medical social workers from European countries, United States of America, Canada, and Australia, those had undergone spiritual training, and those who had higher self-reported spiritual experiences scale scores were more likely to have the view that spirituality in hospital settings is for facilitating integral healing and wellness of patients and were more likely to prefer spiritual packages of New Age movements as the form of spiritual program, understand spiritual assessment as assessing the patients' spiritual starting point, to then build on further interventions and were likely to attest the understanding of spiritual techniques as mindfulness techniques. Finally they were also likely to understand the spiritual goals of intervention in a holistic way, that is, as that of integral healing, growth of consciousness and promoting overall well-being of patients vis-a-vis only coping and coming to terms with health adversities. Results of the structural equation models also showed covariances between religion, spirituality training, and scores on the self-reported spiritual experiences scale, having thus a set of compounding effects on social workers' views on spiritual interventions in hospitals. The implications of the results for health care social work practice and curriculum are discussed. PMID- 27367141 TI - The Framing of Women and Health Disparities: A Critical Look at Race, Gender, and Class from the Perspectives of Grassroots Health Communicators. AB - As women's health has received significant political and media attention recently, I proposed an expanded structural theory of women's communication about health. Women's health communication and critical race and systemic racism research framed this study. I interviewed 15 communicators and community health workers from grass-roots organizations focused on women's health to learn of their challenges of communicating with women from communities experiencing health disparities. Findings suggest that communicators face difficulties in developing meaningful messaging for publics because of disjunctures between medical and community frames, issues in searching for health among women's many priorities, Whiteness discourses imposed on publics' experiences, and practices of correcting for power differentials. A structural theory of women's health communication, then, consists of tenets around geographic, research/funding, academic/industry, and social hierarchies. Six frames suggesting racial biases about women and health disparities are also defined. This study also includes practical solutions in education, publishing, and policy change for addressing structural challenges. PMID- 27367142 TI - Targeted therapies in thyroid cancer: an extensive review of the literature. AB - INTRODUCTION: Patients with progressive, metastatic, RAI-refractory differentiated thyroid cancer (DTC), as well as patients with advanced medullary (MTC) and anaplastic thyroid cancer represent a cohort for which therapeutic options are limited. The recent discoveries in the molecular mechanisms implicated in TC have provided insight of the pathogenesis and progression of disease. In that respect, targeted therapies have emerged as a promising alternative for the treatment of those patients. AREAS COVERED: Tyrosine Kinase Inhibitors (TKIs) have been studied extensively in TC: sorafenib and lenvatinib have been approved by the FDA for the treatment of metastatic, RAI-refractory DTC, while vandetanib and cabozantinib are FDA approved for use in advanced MTC. Moreover, several additional TKIs, multi-targeted or specific, are currently under investigation in TC. The current manuscript provides an extensive review of the literature regarding targeted therapies in TC including the rationale behind their use, the clinical trials and an expert opinion on their use. Literature in English appearing at PubMed was thoroughly reviewed, especially manuscripts of the last 5 years. Expert commentary: Patients with advanced, progressive, metastatic TC should be evaluated for enrollment in a clinical trial or should be placed on treatment with one of the FDA- and EMA- approved agents. PMID- 27367144 TI - Correlation of Peripapillary Choroidal Thickness and Retinal Nerve Fiber Layer Thickness in Normal Subjects and in Patients with Glaucoma. AB - PURPOSE: This study was designed to compare the normal and glaucomatous eyes regarding retinal nerve fiber layer (RNFL) thickness and peripapillary choroidal thickness (PCT), and to investigate the correlation of RNFL thickness and PCT. SUBJECTS AND METHODS: Subjects were selected as a convenience sample of those from a tertiary referral practice of glaucoma. Thirty-two glaucomatous eyes were accepted as group 1; 30 normal eyes were accepted as group 2. Groups were compared for RNFL thickness and PCT. Correlations of RNFL thickness and PCT were assessed for each peripapillary location. RESULTS: Mean inferior and superior RNFL thickness in group 1 were significantly lower than the control group; mean thicknesses of temporal and nasal quadrants were not different in the two groups. Mean PCT at 500 um distance in the inferior, at 1500 um distance in the superior, at 500, 1000, and 1500 um distance in the temporal, and at 1000 and 1500 um distance in nasal quadrants were found to be significantly thinner in the glaucoma group compared with the control group. Retinal nerve fiber thickness was strongly correlated with PCT at all points of inferior quadrants at 500 um distance in the superior. There was no correlation between RNFL thickness and PCT at any point in the control group. CONCLUSION: Peripapillary choroidal thickness was thinner in glaucomatous eyes compared with normal eyes. Correlation of PCT and RNFL thickness found in patients with glaucoma did not exist in normal subjects. PMID- 27367143 TI - The Impact of Cardiac Motion on Aortic Valve Flow Used in Computational Simulations of the Thoracic Aorta. AB - Advancements in image-based computational modeling are producing increasingly more realistic representations of vasculature and hemodynamics, but so far have not compensated for cardiac motion when imposing inflow boundary conditions. The effect of cardiac motion on aortic flow is important when assessing sequelae in this region including coarctation of the aorta (CoA) or regurgitant fraction. The objective of this investigation was to develop a method to assess and correct for the influence of cardiac motion on blood flow measurements through the aortic valve (AoV) and to determine its impact on patient-specific local hemodynamics quantified by computational fluid dynamics (CFD). A motion-compensated inflow waveform was imposed into the CFD model of a patient with repaired CoA that accounted for the distance traveled by the basal plane during the cardiac cycle. Time-averaged wall shear stress (TAWSS) and turbulent kinetic energy (TKE) values were compared with CFD results of the same patient using the original waveform. Cardiac motion resulted in underestimation of flow during systole and overestimation during diastole. Influences of inflow waveforms on TAWSS were greatest along the outer wall of the ascending aorta (AscAo) (~30 dyn/cm2). Differences in TAWSS were more pronounced than those from the model creation or mesh dependence aspects of CFD. TKE was slightly higher for the motion compensated waveform throughout the aortic arch. These results suggest that accounting for cardiac motion when quantifying blood flow through the AoV can lead to different conclusions for hemodynamic indices, which may be important if these results are ultimately used to predict patient outcomes. PMID- 27367145 TI - It All Starts with a Sandwich: Identification of Sialidases with Trans Glycosylation Activity. AB - Sialidases (3.2.1.18) may exhibit trans-sialidase activity to catalyze sialylation of lactose if the active site topology is congruent with that of the Trypanosoma cruzi trans-sialidase (EC 2.4.1.-). The present work was undertaken to test the hypothesis that a particular aromatic sandwich structure of two amino acids proximal to the active site of the T. cruzi trans-sialidase infers trans sialidase activity. On this basis, four enzymes with putative trans-sialidase activity were identified through an iterative alignment from 2909 native sialidases available in GenBank, which were cloned and expressed in Escherichia coli. Of these, one enzyme, SialH, derived from Haemophilus parasuis had an aromatic sandwich structure on the protein surface facing the end of the catalytic site (Phe168; Trp366), and was indeed found to exhibit trans-sialidase activity. SialH catalyzed production of the human milk oligosaccharide 3' sialyllactose as well as the novel trans-sialylation product 3-sialyllactose using casein glycomacropeptide as sialyl donor and lactose as acceptor. The findings corroborated that Tyr119 and Trp312 in the T. cruzi trans-sialidase are part of an aromatic sandwich structure that confers trans-sialylation activity for lactose sialylation. The in silico identification of trans-glycosidase activity by rational active site topology alignment thus proved to be a quick tool for selecting putative trans-sialidases amongst a large group of glycosyl hydrolases. The approach moreover provided data that help understand structure function relations of trans-sialidases. PMID- 27367146 TI - Correction: TAC102 Is a Novel Component of the Mitochondrial Genome Segregation Machinery in Trypanosomes. AB - [This corrects the article DOI: 10.1371/journal.ppat.1005586.]. PMID- 27367147 TI - Effects of insertion depth on spatial speech perception in noise for simulations of cochlear implants and single-sided deafness. AB - OBJECTIVE: This study evaluated the effects of insertion depth on spatial speech perception in noise for simulations of cochlear implants (CI) and single-sided deafness (SSD). DESIGN: Mandarin speech recognition thresholds were adaptively measured in five listening conditions and four spatial configurations. The original signal was delivered to the left ear. The right ear received either no input, one of three CI simulations in which the insertion depth was varied, or the original signal. Speech and noise were presented at either front, left, or right. STUDY SAMPLE: Ten Mandarin-speaking NH listeners with pure-tone thresholds less than 20 dB HL. RESULTS: Relative to no input in the right ear, the CI simulations provided significant improvements in head shadow benefit for all insertion depths, as well as better spatial release of masking (SRM) for the deepest simulated insertion. There were no significant improvements in summation or squelch for any of the CI simulations. CONCLUSIONS: The benefits of cochlear implantation were largely limited to head shadow, with some benefit for SRM. The greatest benefits were observed for the deepest simulated CI insertion, suggesting that reducing mismatch between acoustic and electric hearing may increase the benefit of cochlear implantation. PMID- 27367148 TI - Highly sensitive avidin-biotin ELISA for detection of nandrolone and testosterone in dietary supplements. AB - Avidin-biotin technology was used for the implementation of an enzyme-linked immunosorbent assay (AB-ELISA) as a sensitive method for the detection of anabolic androgenic steroids (AAS) present in dietary supplements. Using click chemistry, novel haptens (linker-optimized biotinylated nandrolone (NT) and testosterone (T) at positions C-3 and C-17, respectively) were designed and synthesized to be then applied as four different immobilized competitors in a proposed set of four indirect competitive AB-ELISAs. Four rabbit polyclonal antibodies of various specificities were prepared using four different immunogens synthesized from C-3 and C-17 carboxymethyloxime and hemisuccinate derivatives of NT and T, respectively. Assembled AB-ELISAs were characterized to establish method parameters such as a half-maximum inhibition concentration (0.18-12.99 ng/mL), limit of detection (0.004-0.032 ng/mL) and linear working range (the best with 0.02-1.38 ng/mL). The stability of the set simulating storage in different conditions was demonstrated. Cross reactivity (CR) was tested for 59 steroids including both endogenous and synthetic analogues in four assembled AB-systems. The focus was placed on the practical use of the method in detection of various AAS in 49 samples of counterfeit dietary supplements. The concordance between ultra high performance liquid chromatography-mass spectrometry (UHPLC-MS) and the CR corrected data from AB-ELISA indicated the potential of this method even to quantification of T propionate, NT phenyl propionate, and NT decanoate in such a complex matter. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27367149 TI - Mixing at the microscale: Power input in shaken microtiter plates. AB - Power input and local energy dissipation are crucial parameters for the engineering characterization of mixing and fluid dynamics at the microscale. Since hydrodynamic stress is solely dependent on the maximum power input, we adapted the clay/polymer method to obtain flock destruction kinetics in six-, 24 , and 96-well microtiter plates on orbital shakers. We also determined the specific power input using calorimetry and found that the power input is at the same order of magnitude for the six- and 96-well plates and the laboratory-scale stirred tank reactor, with 40 to 90 W/m3 (Re' = 180 to 440), 40 to 140 W/m3 (Re' = 320 to 640), and 30 to 50 W/m3 (Re = 4000 to 8500), respectively. All of these values are significantly below 450 to 2100 W/m3 determined for the pilot-scale reactor. The hydrodynamic stress differs significantly between the different formats of MTPs, as the 96-well plates showed very low shear stress on the shaker with a shaking amplitude of 3 mm. Thus, the transfer of mixing conditions from the microtiter plate to small-scale and pilot-scale reactors must be undertaken with care. Our findings, especially the power input determined by the calorimetric method, show that the hydrodynamic conditions in laboratory- and pilot-scale reactors cannot be reached. PMID- 27367150 TI - Effects of sodium pentaborate pentahydrate exposure on Chlorella vulgaris growth, chlorophyll content, and enzyme activities. AB - Sodium pentaborate pentahydrate (SPP) is a rare mineral. In this study, SPP was synthesized from boric acid and borax through low-temperature crystallization, and its effects on the growth of the alga, Chlorella vulgaris (C. vulgaris) were assessed. The newly synthesized SPP was characterized by chemical analysis, X-ray diffraction, Fourier-transform infrared spectroscopy, Raman spectroscopy, thermogravimetric analysis, and differential thermal analysis. The changes in C. vulgaris growth, chlorophyll content, and enzyme activities upon exposure to SPP for 168h were evaluated. Results showed that SPP treatment was detrimental to C. vulgaris growth during the first 24-120h of exposure. The harmful effects, however, diminished over time (168h), even at an effective medium concentration of 226.37mg BL(-1) (the concentration of boron applied per liter of culture medium). A similar trend was observed for chlorophyll content (chlorophyll a and b) and indicated that the photosynthesis of C. vulgaris was not affected and that high levels of SPP may even promote chlorophyll synthesis. Superoxide dismutase and catalase activities of C. vulgaris increased during 24-120h exposure to SPP, but these activities gradually decreased as culture time progressed. In other words, the initial detrimental effects of synthetic SPP on C. vulgaris were temporary and reversible. This research provides a scientific basis for applications of SPP in the environment. PMID- 27367151 TI - Effects of leisure-time and occupational physical activities on 20-year incidence of acute myocardial infarction: mediation and interaction. AB - OBJECTIVES: This study aimed to disentangle the interplay between occupational physical activity (OPA) and leisure-time physical activity (LTPA) in affecting cardiovascular health by examining: (i) interactions between OPA and LTPA and their combined effect on 20-year incidence of acute myocardial infarction (AMI) and (ii) the effect of OPA on AMI that is mediated through LTPA. METHODS: We analyzed data on 1891 men, aged 42-60 years at baseline, from the prospective Kuopio Ischemic Heart Disease Risk Factor Study. OPA was measured as relative aerobic strain (RAS), accounting for workers' cardiorespiratory fitness. Averaged 12-month LTPA and potential confounders were assessed by questionnaires. Analyses were stratified by the presence of ischemic heart disease (IHD) at baseline. RESULTS: We found potential multiplicative, but not additive, interactions between OPA and LTPA among men with IHD. The multivariable Cox model, adjusted for age, education, smoking, alcohol consumption, psychosocial job factors, and participation in an unrelated drug trial, showed that high OPA positively predicted AMI at low LTPA levels for both men with and without IHD: hazard ratio (HR) 1.27 [95% confidence interval (95% CI) 0.96-1.68] and HR 1.59 (95% CI 0.99 1.68), respectively. The combination of high OPA and low LTPA constituted the group associated with the highest risk for AMI, irrespective of IHD status. LTPA was not independently predictive of AMI and did not mediate the impact of OPA on AMI. CONCLUSIONS: LTPA interacted with OPA on the multiplicative scale only. LTPA did not mediate the effect of OPA on AMI. PMID- 27367152 TI - Dual-Responsive Carbon Dots for Tumor Extracellular Microenvironment Triggered Targeting and Enhanced Anticancer Drug Delivery. AB - In this work, pH/redox dual-responsive carbon dots (CDs-RGD-Pt(IV)-PEG) were fabricated for tumor extracellular microenvironment triggered targeting and enhanced anticancer drug delivery. The system consists of fluorescent carbon dots as imaging-guided drug nanocarriers, cisplatin(IV) as prodrug, and RGD peptide as active targeting ligand, which is covered by monomethoxypolyethylene glycol (mPEG) through tumor extracellular pH (6.5-6.8) responsive benzoic-imine bond. The drug nanocarriers could be tracked by multicolor fluorescence of carbon dots. After the hydrolysis of benzoic-imine bond at the tumor extracellular pH to expose the inner targeting RGD peptide, the drug nanocarriers showed effective uptake by cancer cells through RGD-integrin alphavbeta3 (ligand-receptor) interaction. Upon the internalization, the loaded cisplatin(IV) prodrug was reduced to cytotoxic cisplatin in reductive cytosol of cancer cells to exhibit therapeutic effects. Confocal imaging, flow cytometry, and cell viability assays using CDs-RGD-Pt(IV)-PEG were performed to reveal the enhanced uptake and better therapeutic efficiency to cancer cells with high integrin alphavbeta3 expression at tumor extracellular pH than that in physiological condition. The developed CDs RGD-Pt(IV)-PEG offers a new strategy to provide safe and effective therapeutic agents based on carbon dots for promising cancer therapy. PMID- 27367153 TI - Characterization and in vitro evaluation of nimotuzumab conjugated with cisplatin loaded liposomes. AB - In this paper, we report the conjugation of the humanized monoclonal antibody nimotuzumab with cisplatin-loaded liposomes and the in vitro evaluation of its affinity for tumor cells. The conjugation procedure was performed through derivatization of nimotuzumab with N-succinimidyl S-acetylthioacetate (SATA) followed by a covalent attachment with maleimide groups at the end of PEG-DSPE chains located at the membrane of pre-formed liposomes. Confocal microscopy was performed to evaluate the immunoliposome affinity for EGFR antigens from human epidermoid carcinoma (A-431) and normal lung (MRC-5) cell lines. Results showed that the procedures implemented in this work do not affect the capability of the nimotuzumab-immunoliposomes to recognize the tumor cells, which overexpress the EGFR antigens. PMID- 27367154 TI - Vorinostat in refractory soft tissue sarcomas - Results of a multi-centre phase II trial of the German Soft Tissue Sarcoma and Bone Tumour Working Group (AIO). AB - INTRODUCTION: New treatment options for patients with metastatic Soft Tissue Sarcoma are urgently needed. Preclinical studies suggested activity of vorinostat, a histone deacetylase inhibitor. METHODS: A multi-centre, open-label, non-randomised phase II trial to investigate the efficacy and safety of vorinostat in patients with locally advanced or metastatic Soft Tissue Sarcoma failing 1st-line anthracycline-based chemotherapy was initiated. Patients were treated with vorinostat 400 mg po qd for 28 d followed by a treatment-free period of 7 d, representing a treatment cycle of 5 weeks. Restaging was performed every three cycles or at clinical progression. RESULTS: Between 06/10 and 09/13, 40 Soft Tissue Sarcoma patients were treated with vorinostat at seven participating centres. Patients had received 1 (n=8, 20%), 2 (n=10, 25%) or >=3 (n=22, 55%) previous lines of chemotherapy. Best response after three cycles of treatment was stable disease (n=9, 23%). Median progression-free survival and overall survival were 3.2 and 12.3 months, respectively. Six patients showed long-lasting disease stabilisation for up to ten cycles. Statistical analyses failed to identify baseline predictive markers in this subgroup. Major toxicities (grade >=III) included haematological toxicity (n=6, 15%) gastrointestinal disorders (n=5, 13%), fatigue (n=4, 10%), musculoskeletal pain (n=4, 10%), and pneumonia (n=2, 5%). CONCLUSION: In a heavily pre-treated patient population, objective response to vorinostat was low. However, a small subgroup of patients had long-lasting disease stabilisation. Further studies aiming to identify predictive markers for treatment response as well as exploration of combination regimens are warranted. TRIAL REGISTRATION: NCT00918489 (ClinicalTrials.gov) EudraCT-number: 2008-008513 19. PMID- 27367155 TI - Effectiveness of rotavirus vaccine in preventing severe gastroenteritis in young children according to socioeconomic status. AB - In 2011, the monovalent rotavirus vaccine was introduced into a universal immunization program in Quebec (Canada). This retrospective cohort study assessed vaccine effectiveness (VE) in preventing acute gastroenteritis (AGE) and rotavirus gastroenteritis (RVGE) hospitalizations among children <3 y living in the Quebec Eastern Townships region according to socioeconomic status (SES). Data were gathered from a tertiary hospital database paired with a regional immunization registry. Three cohorts of children were followed: (1) vaccinated children born in post-universal vaccination period (2011-2013, n = 5,033), (2) unvaccinated children born in post-universal vaccination period (n = 1,239), and (3) unvaccinated children born in pre-universal vaccination period (2008-2010, n = 6,436). In each cohort, AGE and RVGE hospitalizations were identified during equivalent follow-up periods to calculate VE globally and according to neighborhood-level SES. Using multivariable logistic regression, adjusted odds ratios (OR) were computed to obtain VE (1-OR). Adjusted VE of 2 doses was 62% (95% confidence interval [CI]: 37%-77%) and 94% (95%CI: 52%-99%) in preventing AGE and RVGE hospitalization, respectively. Stratified analyses according to SES showed that children living in neighborhoods with higher rates of low-income families had significantly lower VE against AGE hospitalizations compared to neighborhoods with lower rates of low-income families (30% vs. 78%, p = 0.027). Our results suggest that the rotavirus vaccine is highly effective in preventing severe gastroenteritis in young children, particularly among the most well-off. SES seems to influence rotavirus VE, even in a high-income country like Canada. Further studies are needed to determine factors related to lower rotavirus VE among socioeconomically disadvantaged groups. PMID- 27367156 TI - Automated bedside dispensing machine may significantly reduce nurses' medication administration errors in inpatient settings. PMID- 27367157 TI - Biography: Edward William Schlag. PMID- 27367158 TI - Proton-Coupled Electron Transfer in the Reduction of Carbonyls by Samarium Diiodide-Water Complexes. AB - Reduction of carbonyls by SmI2 is significantly impacted by the presence of water, but the fundamental step(s) of initial transfer of a formal hydrogen atom from the SmI2-water reagent system to produce an intermediate radical is not fully understood. In this work, we provide evidence consistent with the reduction of carbonyls by SmI2-water proceeding through proton-coupled electron transfer (PCET). Combined rate and computational studies show that a model aldehyde and ketone are likely reduced through an asynchronous PCET, whereas reduction of a representative lactone occurs through a concerted PCET. In the latter case, concerted PCET is likely a consequence of significantly endergonic initial electron transfer. PMID- 27367159 TI - Effect of spironolactone on patients with resistant hypertension and obstructive sleep apnea. AB - OBJECTIVE: To examine whether spironolactone could reduce the severity of obstructive sleep apnea (OSA) and lower blood pressure in patients with resistant hypertension. METHODS: This was a blank-controlled, single-center study. Patients with resistant hypertension and moderate-to-severe OSA (apnea-hypopnea index >15 events/h) were enrolled and randomly assigned to the therapy or control group. Patients in the therapy group were administered spironolactone 20 mg once daily (up to 40 mg once daily for 4 weeks, if required) in addition to original antihypertensive medication. Follow-up was 12 weeks. RESULTS: Thirty patients were enrolled (n = 15 per group). After 12 weeks of follow-up, apnea-hypopnea index (21.8 +/- 15.7 vs. 1.8 +/- 12.8, p < 0.05), hypopnea index (9.8 +/- 11.1 vs. -2.7 +/- 16.8, p < 0.05), oxygen desaturation index (20.8 +/- 15.0 vs. 0.3 +/ 16.1, p < 0.05), clinical blood pressure, ambulatory blood pressure, and plasma aldosterone level (9.8 +/- 6.3 vs. 2.9 +/- 6.7, p < 0.05) were reduced significantly in the therapy group compared with the control group. No side effects were reported. CONCLUSIONS: Spironolactone reduced the severity of OSA and reduced blood pressure in resistant hypertension patients with moderate-to severe OSA. These findings may assist in the treatment of OSA in patients with resistant hypertension. PMID- 27367160 TI - Molecular Pathogenic Basis for GABRG2 Mutations Associated With a Spectrum of Epilepsy Syndromes, From Generalized Absence Epilepsy to Dravet Syndrome. AB - OBJECTIVE: In this review article, we focus on the molecular pathogenic basis for genetic generalized epilepsies associated with mutations in the inhibitory gamma aminobutyric acid (GABAA) receptor gamma2 subunit gene, GABRG2 (OMIM 137164), an established epilepsy gene. OBSERVATIONS: The gamma-aminobutyric acid (GABAA) receptor gamma2 subunit gene, GABRG2, is abundantly expressed in the mammalian brain, and its encoded gamma2 subunit is assembled into alphabetagamma2 receptors, which are the major GABAA receptor isoforms in the brain. The gamma2 subunits have a critical role in GABAA receptor trafficking and clustering at synapses. They reside inside the endoplasmic reticulum after synthesis, where they oligomerize with other binding partners, such as alpha and beta subunits, and further assemble into pentameric receptors. Only correctly assembled receptors can traffic beyond the endoplasmic reticulum and reach the cell surface and synapses, where they conduct chloride ion current when activated by GABA. Mutations in GABRG2 have been associated with simple febrile seizures and with genetic epilepsy syndromes, including childhood absence epilepsy, generalized epilepsy with febrile seizures plus, and Dravet syndrome or severe myoclonic epilepsy in infancy. The mutations include missense, nonsense, and frameshift mutations, as well as splice-site and deletion mutations. The mutations have been identified in both coding and noncoding sequences like splice sites. In the coding sequence, these mutations are found in multiple locations, including the extracellular N-terminus, transmembrane domains, and transmembrane 3 transmembrane 4 intracellular loop. All of these mutations reduced channel function but to different extents and by diverse mechanisms, including nonsense mediated messenger RNA decay, endoplasmic reticulum-associated protein degradation, dominant negative suppression of partnering subunits, mutant subunit aggregation causing cell stress and cell death, and gating defects. CONCLUSIONS AND RELEVANCE: We conclude that the epilepsy phenotypic heterogeneity associated with GABRG2 mutations may be related to the extent of the reduction of GABAA receptor channel function and the differential dominant negative suppression, as well to toxicity related to the metabolism of mutant subunit proteins resulting from each mutant gamma2 subunit, in addition to different genetic backgrounds. PMID- 27367162 TI - Fabry Disease Biomarkers: Analysis of Urinary Lyso-Gb3 and Seven Related Analogs Using Tandem Mass Spectrometry. AB - Fabry disease is an X-linked lysosomal storage disorder caused by the absence or reduction of the enzyme alpha-galactosidase A activity. Currently, globotriaosylsphingosine (lyso-Gb3 ) and globotriaosylceramide (Gb3 ) are used as biomarkers to diagnose and monitor Fabry patients. However, recent metabolomic studies have shown that several glycosphingolipids are also elevated in biological fluids of affected patients and may be related to disease manifestations. This unit describes a multiplex methodology targeting the analysis of urinary lyso-Gb3 and seven structurally related analogs. A solid phase extraction process is performed, then lyso-Gb3 and its analogs are analyzed simultaneously with an internal standard by ultra-performance liquid chromatography (UPLC) coupled to a tandem mass spectrometry (MS/MS) system. This methodology can be useful for the diagnosis of Fabry patients, including patients with cardiac variant mutations, but also to monitor the efficacy of therapeutic interventions, considering that lyso-Gb3 analogs are more elevated than lyso-Gb3 itself in urine. (c) 2016 by John Wiley & Sons, Inc. PMID- 27367161 TI - Engineering Large Animal Species to Model Human Diseases. AB - Animal models are an important resource for studying human diseases. Genetically engineered mice are the most commonly used species and have made significant contributions to our understanding of basic biology, disease mechanisms, and drug development. However, they often fail to recreate important aspects of human diseases and thus can have limited utility as translational research tools. Developing disease models in species more similar to humans may provide a better setting in which to study disease pathogenesis and test new treatments. This unit provides an overview of the history of genetically engineered large animals and the techniques that have made their development possible. Factors to consider when planning a large animal model, including choice of species, type of modification and methodology, characterization, production methods, and regulatory compliance, are also covered. (c) 2016 by John Wiley & Sons, Inc. PMID- 27367163 TI - Tandem Mass Spectrometry Quantitation of Lyso-Gb3 and Six Related Analogs in Plasma for Fabry Disease Patients. AB - Fabry disease is an X-linked lysosomal storage disorder, caused by a deficit in alpha-galactosidase A enzyme activity, leading to the storage of sphingolipids such as globotriaosylsphingosine (lyso-Gb3 ), globotriaosylceramide (Gb3 ), and galabiosylceramide (Ga2 ) in organs, tissues and biological fluids. A recent metabolomic study performed in plasma revealed lyso-Gb3 analogs as novel Fabry disease biomarkers. These molecules correspond to lyso-Gb3 with different chemical modifications on the sphingosine chain (-C2 H4 , -H2 , +O, +H2 O, +H2 O2, and +H2 O3 ). An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the multiplex analysis of lyso-Gb3 and its 6 analogs in plasma. The samples are prepared by solid phase extraction using mixed-mode strong cation exchange (MCX) cartridges. An in-house synthesized N-glycinated lyso-Gb3 derivative was used for the internal standard. The limits of detection (LODs) measured for lyso-Gb3 and its analogs ranged from 0.06 to 0.29 nM. (c) 2016 by John Wiley & Sons, Inc. PMID- 27367164 TI - Quality Control for the Illumina HumanExome BeadChip. AB - The Illumina HumanExome BeadChip and other exome-based genotyping arrays offer inexpensive genotyping of some 240,000 mostly nonsynonymous coding variants across the human genome. The HumanExome chip, with its highly non-uniform distribution of markers and emphasis on rare coding variants, presents some unique challenges for quality control (QC) and data cleaning. Here, we describe QC procedures for HumanExome data, with examples of challenges specific to exome arrays from our experience cleaning a data set of ~7,500 samples from the NEIGHBORHOOD Consortium. We focus on standard procedures for QC of genome-wide array data including genotype calling, sex verification, sample identity verification, relationship checking, and population structure that are complicated by the HumanExome panel's enrichment in rare, exonic variation. (c) 2016 by John Wiley & Sons, Inc. PMID- 27367165 TI - Integrative Analysis of Histone ChIP-seq and RNA-seq Data. AB - The R package epigenomix has been designed to detect differentially transcribed gene isoforms that, in addition, exhibit altered histone modifications at their respective genomic loci. The package provides methods to map histone ChIP-seq profiles to isoforms and estimate their transcript abundances from RNA-seq data. Based on the differences observed between case and control samples in the RNA-seq and ChIP-seq data, a correlation measure is calculated for each isoform. The distribution of this correlation measure is further investigated by a Bayesian mixture model to (i) reveal the relationship between the studied histone modification and transcriptional activity, and (ii) detect specific isoforms with differences in both transcription values and histone modifications. The method is designed for experiments with a few or no replicates, and is superior to separate analyses of both data types in that setting. This unit illustrates the integrative analysis of ChIP-seq and RNA-seq data with epigenomix. (c) 2016 by John Wiley & Sons, Inc. PMID- 27367166 TI - Efficient Generation of Hypothalamic Neurons from Human Pluripotent Stem Cells. AB - The hypothalamus comprises neuronal clusters that are essential for body weight regulation and other physiological functions. Insights into the complex cellular physiology of this region of the brain are critical to understanding the pathogenesis of obesity, but human hypothalamic cells are largely inaccessible for direct study. Here we describe a technique for generation of arcuate-like hypothalamic neurons from human pluripotent stem (hPS) cells. Early activation of SHH signaling and inhibition of BMP and TGFbeta signaling, followed by timed inhibition of NOTCH, can efficiently differentiate hPS cells into NKX2.1+ hypothalamic progenitors. Subsequent incubation with BDNF induces the differentiation and maturation of pro-opiomelanocortin and neuropeptide Y neurons, which are major cell types in the arcuate hypothalamus. These neurons have molecular and cellular characteristics consistent with arcuate neurons. (c) 2016 by John Wiley & Sons, Inc. PMID- 27367168 TI - Accelerated Biodegradation of Agriculture Film Based on Aromatic-Aliphatic Copolyester in Soil under Mesophilic Conditions. AB - A study was conducted on the biodegradation of aromatic-aliphatic copolyester based agricultural film in soil at 25 degrees C. The polymer is known to be biodegradable under composting conditions although rather recalcitrant under mesophilic conditions. The material investigated comprised of the copolyester filled with approximately 25% of starch containing biodegradable plasticizers, and its behavior was compared to the corresponding material without the filler. Mineralization followed by CO2 production merely reached the point of about 6% after 100 days of incubation in the pure copolyester film, whereas the value of around 53% was recorded for the filled copolyester film, which exceeded the readily biodegradable starch filler content in the material by more than 20% and could be accounted for biodegradation of the copolyester. It was suggested that the accelerated copolyester biodegradation in the starch-filled material was most likely explained by the increase in the active surface area of the material available for the microbial attack after biodegradation of the filler. The results were supported by changes in molecular weight distributions of the copolyester and observations made by several microscopic techniques. These findings encourage further development of biodegradable agricultural films based on this material. PMID- 27367167 TI - Sequence Variant Descriptions: HGVS Nomenclature and Mutalyzer. AB - Consistent and unambiguous description of sequence variants is essential to report and exchange information on the analysis of a genome, in particular in DNA diagnostics. The HGVS nomenclature-recommendations for the description of sequence variants as originally proposed by the Human Genome Variation Society has gradually been accepted as the international standard for variant description. In this unit, we describe the current recommendations (HGVS version 15.11) regarding how to describe variants at the DNA, RNA, and protein level. We explain the rationale and give example descriptions for all variant types: substitution, deletion, duplication, insertion, inversion, conversion, and complex, as well as special types occurring only on the RNA (splicing) or protein level (nonsense, frame shift, extension). Finally, we point users to available support tools and give examples for the use of the freely available Mutalyzer suite. An extensive version of the HGVS recommendations is available online at http://varnomen.hgvs.org/. (c) 2016 by John Wiley & Sons, Inc. PMID- 27367169 TI - Unexpected formation of pi-expanded isoquinoline from anthracene possessing four electron-donating groups via the Duff reaction. AB - New synthetic methods leading towards pi-expanded heterocycles are sought after mainly due to their promising opto-electronic properties. Subjecting 1,5,9,10 tetramethoxyanthracene to the modern Duff reaction conditions led to the formation of a compound possessing the 2-azabenzoanthrone (dibenzo[de,h]isoquinolin-7-on) skeleton instead of the expected dialdehyde. This non-typical course of reaction can be rationalized by the double electrophilic aromatic substitution at two neighboring electron-rich positions of anthracene followed by oxidation of the resulting intermediate to form a pyridine ring. Optical studies supported by the quantum chemistry calculations indicated the lack of excited-state intramolecular proton transfer (ESIPT); for energy reasons, only one tautomeric form, with a hydrogen atom bonded to one of the two nearby oxygen atoms, was populated in the electronic ground S0 and in the excited S1 states. Nonradiative depopulation of the S1 state proceeded via internal conversion stimulated by the presence of the low frequency vibrational modes. Our serendipitous discovery represents the most complex case of rearrangement of aromatic compounds under Duff reaction conditions and could help to design analogous processes. At the same time this is the simplest method for the synthesis of derivatives of 2-azabenzoanthrone. PMID- 27367170 TI - Assessment of Accuracy of Patient-Initiated Differential Diagnosis Generation by Google Reverse Image Searching. PMID- 27367171 TI - Isolated Right Ventricular Myocardial Infarction: A Sheep in Wolf's Clothing. PMID- 27367172 TI - Organic Bioelectronics: Bridging the Signaling Gap between Biology and Technology. AB - The electronics surrounding us in our daily lives rely almost exclusively on electrons as the dominant charge carrier. In stark contrast, biological systems rarely use electrons but rather use ions and molecules of varying size. Due to the unique combination of both electronic and ionic/molecular conductivity in conducting and semiconducting organic polymers and small molecules, these materials have emerged in recent decades as excellent tools for translating signals between these two realms and, therefore, providing a means to effectively interface biology with conventional electronics-thus, the field of organic bioelectronics. Today, organic bioelectronics defines a generic platform with unprecedented biological recording and regulation tools and is maturing toward applications ranging from life sciences to the clinic. In this Review, we introduce the field, from its early breakthroughs to its current results and future challenges. PMID- 27367173 TI - Preservation of cognitive and musical abilities of a musician following surgery for chronic drug-resistant temporal lobe epilepsy: a case report. AB - Mesial temporal lobe epilepsy (TLE) affects a range of cognitive functions and musical abilities. We report a 16-year-old boy diagnosed with drug-resistant right-medial TLE. He is a professional musician, trained in Carnatic classical music. Clinical, electrophysiological, magnetic resonance imaging (MRI) and positron emission tomography evaluation localized the seizure focus to the right medial temporal lobe. Patient underwent detailed neuropsychological evaluation and functional MRI (fMRI) for musical abilities prior to surgery. He underwent an awake craniotomy and tailored resection of lateral neocortex as well as amygdalohippocampectomy under guidance of cortical stimulation and clinical monitoring. The superior temporal gyrus where activation was revealed on task based fMRI was preserved. At 16-month follow-up, there was no seizure recurrence and his cognitive functions including musical abilities did not deteriorate with surgery. The task-based fMRI while listening to music revealed bilateral frontotemporal activation. There was evidence of increased left frontotemporal connectivity during the postsurgical period in the resting state fMRI. It is hypothesized that the intact neuropsychological and musical abilities might be as a result of intense musical training from an early age despite the illness leading to functional and neural adaptation of the brain might have contributed to his preserved cognitive functions and musical skills. Intense musical training at a young age perhaps not only honed a range of cognitive functions but also resulted in functionally more efficient cognitive networks despite the surgical resection. PMID- 27367174 TI - Ultraviolet Photochemistry of Co(III)L(H2O)SO3(+) [L = Me6[14]dieneN4,[14]andN4] Complexes. Quandaries about the Linkage Isomerization to O-Bonded Sulfite and the Photogeneration of Cobalt(I) in Sequential Biophotonic Photolysis. PMID- 27367175 TI - Effect of resin charged functional group, porosity, and chemical matrix on the long-term pharmaceutical removal mechanism by conventional ion exchange resins. AB - This study attempted to clarify the long-term pharmaceutical removal mechanism from sewage treatment plant effluent during the cyclical adsorption-regeneration operation of 5 commercial resin-based fixed-bed reactors with the simultaneous occurrence of electrostatic interactions and complex non-electrostatic interactions. It examined 12 pharmaceuticals belonging to 10 therapeutic classes with different predominant existing forms and hydrophobicities. Furthermore, the effect of the resin charged functional group (strong-base vs. strong-acid vs. non ionic), porosity (macroporous vs. gel), and chemical matrix (polystyrenic vs. polyacrylic) on the mechanism was investigated to optimize resin properties and achieve higher pharmaceutical removal. The results reported herein indicate the importance of non-electrostatic interactions between pharmaceuticals and the resin backbone during short-term cyclical operation (i.e., the 1st adsorption regeneration cycle). With the development of cyclical operation, however, non electrostatic interaction-induced pharmaceutical removal generally decreased and even disappeared when equilibrium was achieved between the influent and the resin. Despite pharmaceutical therapeutic class or hydrophilicity, anion (or cation) exchange resin preferentially removed those pharmaceuticals that were predominantly present as organic anions (or cations) by ion exchange process during long-term cyclical operation (i.e., >=6 adsorption-regeneration cycles). Besides pharmaceuticals predominantly present as undissociated molecules, some amphoteric pharmaceuticals containing large amounts of zwitterions were also difficult to remove by ion exchange resin. Additionally, neither resin porosity nor chemical matrix had any significant effect on the long-term pharmaceutical removal mechanism. PMID- 27367176 TI - Brominated flame retardants and organochlorine compounds in duplicate diet samples from a Portuguese academic community. AB - Concentrations of persistent organic pollutants (POPs), including polybrominated diphenyl ethers (PBDEs), hexabromocyclododecanes (HBCDDs), polychlorinated biphenyls (PCBs), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB), chlordane compounds (CHLs) and dichlorodiphenyltrichloroethane and its metabolites (DDTs), were measured in duplicate diet samples from 21 volunteers at a Portuguese academic community (University of Aveiro). Overall, the levels of the target compounds were low, with detection frequencies varying widely depending on the compounds and with brominated flame retardants (BFRs) registering the lowest detection frequencies. Among PCB congeners, nondioxin-like PCBs were predominant and detected in the majority of the samples. Organochlorine pesticides were also detected in the majority of the samples, with 100% detection for DDTs and HCHs. Estimated daily intakes (EDIs) were calculated using lower and upper bound estimations, and in both cases values were far below the currently established tolerable daily intakes for PCBs and OCs and the reference doses for PBDEs and HBCDDs. PMID- 27367177 TI - Caffeine impacts in the clam Ruditapes philippinarum: Alterations on energy reserves, metabolic activity and oxidative stress biomarkers. AB - Caffeine is known to be one of the most consumed psychoactive drugs. For this reason, caffeine is continuously released into the environment with potential impacts on inhabiting organisms. The current study evaluated the biochemical alterations induced in the clam species Ruditapes philippinarum after exposure for 28 days to caffeine (0.5, 3.0 and 18.0 MUg/L). The results obtained showed that, with the increasing caffeine concentrations, an increase in clams defense mechanisms (such as antioxidant and biotransformation enzymes activity) was induced which was accompanied by an increase in protein content. Nevertheless, although an increase on defense mechanisms was observed, clams were not able to prevent cells from lipid peroxidation that increased with the increase of caffeine concentration. Furthermore, with the increase of exposure concentrations, clams increased their metabolic activity (measured by electron transport activity), reducing their energy reserves (glycogen content), to fight against oxidative stress. Overall, the present study demonstrated that caffeine may impact bivalves, even at environmentally relevant concentrations, inducing oxidative stress in organisms. The present study is an important contribution to address knowledge gaps regarding the impacts of long-term exposures to pharmaceuticals since most of the studies assessed the effects after acute exposures, most of them up to 96 h. PMID- 27367178 TI - Investigation of spatial distributions and sources of persistent organic pollutants (POPs) in a heavily polluted industrial region using tree components. AB - Spatial distributions of persistent organic pollutants (POPs) were investigated in Iskenderun industrial region in Turkey. POP concentrations were measured in different tree components (i.e., pine needle, branch, bark, and stem) collected at several industrial and background sites (n = 27). Also, air, litter, and soil samples were analyzed to determine the relationship of atmospheric pollutants with tree components, litter, and soil. Spatial variation of measured concentrations and factor analysis showed that the iron-steel plants are the most important POP sources in Iskenderun area. Correlations of ambient air levels to those measured in soil, litter, and tree components were significant showing that POPs are exchanged between atmosphere and these compartments. Results have suggested that tree components, litter and soil could be used to determine the spatial distributions and sources of atmospheric POPs in a region. POP quantities (mg/ha) accumulated in different tree components, litter, and soil were also predicted. Generally, the highest quantities were accumulated by stem and needles. In terms of overall inventory, including trees, litter and soil, the highest accumulated quantities were found in soil followed by trees and litter, indicating that in addition to soil, vegetation is a notable reservoir accumulating POPs. Ambient air POP concentrations were also estimated using a bark/air partitioning model. The estimated/measured ratios were close to 1.0 for several compounds and the results showed that the atmospheric POP concentrations could be estimated from the bark measurements within factors of 0.23-3.07, 1.02 6.67, 0.63-7.44, 1.07-3.37 for polycyclic aromatic hydrocarbons, polychlorinated biphenyls, polychlorinated naphthalenes, and polybrominated diphenyl ethers, respectively. PMID- 27367179 TI - An integral equation and simulation study of hydrogen inclusions in a molecular crystal of short-capped nanotubes. AB - In this work we have assessed the ability of a recently proposed three dimensional integral equation approach to describe the explicit spatial distribution of molecular hydrogen confined in a crystal formed by short-capped nanotubes of C50 H10. To that aim we have resorted to extensive molecular simulation calculations whose results have been compared with our three dimensional integral equation approximation. We have first tested the ability of a single C50 H10 nanocage for the encapsulation of H2 by means of molecular dynamics simulations, in particular using targeted molecular dynamics to estimate the binding Gibbs energy of a host hydrogen molecule inside the nanocage. Then, we have investigated the adsorption isotherm of the nanocage crystal using grand canonical Monte Carlo simulations in order to evaluate the maximum load of molecular hydrogen. For a packing close to the maximum load explicit hydrogen density maps and density profiles have been determined using molecular dynamics simulations and the three-dimensional Ornstein-Zernike equation with a hypernetted chain closure. In these conditions of extremely tight confinement the theoretical approach has shown to be able to reproduce the three-dimensional structure of the adsorbed fluid with accuracy down to the finest details. PMID- 27367180 TI - What We Don't Talk About When We Talk About Preventing Type 2 Diabetes-Addressing Socioeconomic Disadvantage. PMID- 27367181 TI - Metal-Free Synthesis of Fully Substituted Pyridines via Ring Construction Based on the Domino Reactions of Enaminones and Aldehydes. AB - An unprecedented domino reaction involving primary enaminones/enaminoesters and aldehydes has been developed for the synthesis of fully substituted pyridines. The construction of the products has been accomplished via the cascade generation of two C-C and one C-N bond by simply using TfOH as a promoter. PMID- 27367182 TI - A conversation with Laurie Glimcher. PMID- 27367183 TI - Current concepts of severe asthma. AB - The term asthma encompasses a disease spectrum with mild to very severe disease phenotypes whose traditional common characteristic is reversible airflow limitation. Unlike milder disease, severe asthma is poorly controlled by the current standard of care. Ongoing studies using advanced molecular and immunological tools along with improved clinical classification show that severe asthma does not identify a specific patient phenotype, but rather includes patients with constant medical needs, whose pathobiologic and clinical characteristics vary widely. Accordingly, in recent clinical trials, therapies guided by specific patient characteristics have had better outcomes than previous therapies directed to any subject with a diagnosis of severe asthma. However, there are still significant gaps in our understanding of the full scope of this disease that hinder the development of effective treatments for all severe asthmatics. In this Review, we discuss our current state of knowledge regarding severe asthma, highlighting different molecular and immunological pathways that can be targeted for future therapeutic development. PMID- 27367185 TI - Evaluation of direct-to-consumer low-volume lab tests in healthy adults. PMID- 27367186 TI - Pancreatic cancer-associated retinoblastoma 1 dysfunction enables TGF-beta to promote proliferation. PMID- 27367184 TI - The host STING pathway at the interface of cancer and immunity. AB - A major subset of human cancers shows evidence for spontaneous adaptive immunity, which is reflected by the presence of infiltrating CD8+ T cells specific for tumor antigens within the tumor microenvironment. This observation has raised the question of which innate immune sensing pathway might detect the presence of cancer and lead to a natural adaptive antitumor immune response in the absence of exogenous infectious pathogens. Evidence for a critical functional role for type I IFNs led to interrogation of candidate innate immune sensing pathways that might be triggered by tumor presence and induce type I IFN production. Such analyses have revealed a major role for the stimulator of IFN genes pathway (STING pathway), which senses cytosolic tumor-derived DNA within the cytosol of tumor-infiltrating DCs. Activation of this pathway is correlated with IFN-beta production and induction of antitumor T cells. Based on the biology of this natural immune response, pharmacologic agonists of the STING pathway are being developed to augment and optimize STING activation as a cancer therapy. Intratumoral administration of STING agonists results in remarkable therapeutic activity in mouse models, and STING agonists are being carried forward into phase I clinical testing. PMID- 27367187 TI - Exploring Factors Influencing Smokers' Information Seeking for Smoking Cessation. AB - This study addressed the factors influencing smokers' information seeking pertaining to the health risks of smoking. In particular, this study aimed to extend the risk information seeking and processing model by taking into account the role of autonomous motivations used to stimulate smokers' information-seeking behavior. The results of a Web-based survey indicated that information insufficiency was positively associated with health information-seeking behavior and that negative affective responses were positively associated with information insufficiency and health information-seeking behavior. In addition, autonomous motivations were positively associated with information insufficiency and information-seeking behavior. The results indicated that risk perception was positively related to autonomous motivations and negative affective response. Finally, informational subjective norm was positively related to autonomous motivations and negative affective responses. The implications of this study for future research are discussed. PMID- 27367188 TI - Small endogenous molecules as moiety to improve targeting of CNS drugs. AB - INTRODUCTION: A major challenge in the development of novel neuro-therapeutic agents is to effectively overcome the blood-brain barrier (BBB), which acts as a 'working dynamic barrier'. The core problem in the treatment of neurodegenerative diseases is failed delivery of potential medicines due to their inadequate permeation rate. Areas covered: The present review gives a summary of endogenous moieties used in synthesizing prodrugs, derivatives and bioisosteric drugs appositely designed to structurally resemble physiological molecular entities able to be passively absorbed or carried by specific carrier proteins expressed at BBB level. In particular, this overview focuses on aminoacidic, glycosyl, purinergic, ureic and acidic fragments derivatives, most of which can take advantage from BBB carrier-mediated transporters, where passive diffusion is not permitted. Expert opinion: In the authors' perspective, further progress in this field could expedite successful translation of new chemical entities into clinical trials. Careful rationalization of the linkage between endogenous molecular structures and putative transporters binding sites could allow to useful work-flows and libraries for synthesizing new BBB-crossing therapeutic substances and/or multifunctional drugs for treatments of central disorders. PMID- 27367189 TI - Akt-dependent and Akt-independent pathways are involved in protein synthesis activation during reloading of disused soleus muscle. AB - INTRODUCTION: The purpose of our study was to assess the contribution of insulin growth factor-1-dependent and phosphatidic acid-dependent signaling pathways to activation of protein synthesis (PS) in rat soleus muscle during early recovery from unloading. METHODS: Wistar rats were divided into: Control, 14HS [14-day hindlimb suspension (HS)], 3R+placebo (3-day reloading + saline administration), 3R+Wort (3-day reloading + wortmannin administration), 3R+But (3-day reloading + 1-butanol administration). SUnSET and Western blot analyses were used in this study. RESULTS: Wortmannin and 1-butanol induced a decrease in protein kinase B (phospho-Akt) and the rate of PS (P < 0.05) versus Control. In 3R+placebo and 3R+Wort, phosphorylation of glycogen synthase kinase 3 beta (phospho-GSK-3beta) was increased versus Control (P < 0.05). Wortmannin administration during reloading did not alter phospho-p70S6K (70 kDa ribosomal protein S6 kinase) versus 3R+placebo. In 3R+But, there was a decline in phospho-GSK-3beta versus 3R+placebo and Control. In 3R+But, there was a decrease in phopho-p70S6K (P < 0.05) versus 3R+placebo. CONCLUSIONS: These results suggest that PS activation during 3-day reloading following 14HS involves both Akt-dependent and Akt independent pathways. Muscle Nerve 55: 393-399, 2017. PMID- 27367191 TI - [The impact of octacalcium phosphate on the dynamics of bone matrix formation in experimental bone defects]. AB - The aim of the study was to assess the interaction of of octacalcium phosphate (OCP) with bone matrix and cells and its impact on the process of bone generation. The survey was conducted on animal model: critical hipbone defect was created in 12 230-250 g Wister rats. The animals were then divided in two groups. In group 1 (6 animals) defect was left to heal under blood clot and in group 2 (6 animals) it was filled with OCP. Three animals with no defect served as a control group. It was showed significant (p<0.05) increase of the area of the newly formed bone tissue and its direct correlation with duration of observation. PMID- 27367190 TI - Pathway analysis of expression-related SNPs on genome-wide association study of basal cell carcinoma. AB - Genome-wide association studies (GWASs) have primarily focused on the association between individual genetic markers and risk of disease. We applied a novel approach that integrates skin expression-related single-nucleotide polymorphisms (eSNPs) and pathway analysis for GWAS of basal cell carcinoma (BCC) to identify potential novel biological pathways. We evaluated the associations between 70,932 skin eSNPs and risk of BCC among 2,323 cases and 7,275 controls of European ancestry, and then assigned them to the pathways defined by KEGG, GO, and BioCarta databases. Three KEGG pathways (colorectal cancer, actin cytoskeleton, and BCC), two GO pathways (cellular component disassembly in apoptosis, and nucleus organization), and four BioCarta pathways (Ras signaling, T cell receptor signaling, natural killer cell-mediated cytotoxicity, and links between Pyk2 and Map Kinases) showed significant association with BCC risk with p-value<0.05 and FDR<0.2. These pathways also ranked at top in sensitivity analyses. Two positive controls in KEGG, the hedgehog pathway and the BCC pathway, showed significant association with BCC risk in both main and sensitivity analyses. Our results indicate that SNPs that are undetectable by conventional GWASs are significantly associated with BCC when tested as pathways. Biological studies of these gene groups suggest their potential roles in the etiology of BCC. PMID- 27367192 TI - [Gender-related marker pathogens of periodontal disease in chronic periodontitis]. AB - By using qPCR system, women as well as men were found to have an equal periodontal pathogen colonization. However, the women are subjected to have a higher risk of chronic periodontitis onsets. Women with the chronic periodontitis usually expose an evident hypercolonization with a single pathogen. P. gingivalis is the most prevalent causative agent of the chronic periodontitis in women but not in men. In health as well as in the chronic periodontitis a complex of periodontal pathogens forms such as P. gingivalis, P. intermedia, T. forsythensis and T. denticola. T. forsythensis demonstrates the highest correlation with the chronic periodontitis onset in men. Our data allow us to prove T. forsythensis playing the key role in the forming of periodontal pathogen complex. PMID- 27367193 TI - [Analysis of the efficacy and safety of electric toothbrushes Oral-B with oscillating-rotating technology in "Healthy smile" program]. AB - The aim of study was to investigate the efficacy and safety of individual oral hygiene in adult patients by regular use of electric toothbrushes with the oscillating-rotating technology basing on data obtained during the implementation of "Healthy Smile" program. Questionnaires of 7022 dentists in Russia and Ukraine were used to assess personal experience of using Oral-B PC 5000 toothbrush. The dental status dynamics after regular use of Oral-B PC 500 tooth brush was evaluatedin 21 088 patients within 12 weeks. It was found out that the use of electric toothbrushes with the oscillating-rotating technology for individual oral hygiene provided a significant improvement of oral hygiene in 93.5+/-0.17%, reducing plaque in 92.5+/-0.18% of patients, improving gingival condition in 87.1+/-0.23% of participants of the Program. The effectiveness of the implemented algorithm of clinical testing and practical application of innovative, high-tech personal oral hygiene tools is proved. PMID- 27367194 TI - [The state of brachiocephalic artery endothelium in individuals with inflammatory periodontal disease and different cardiovascular risks]. AB - The study included 35 patients (19 men and 16 women, aged 35 to 65 years) with chronic generalized severe periodontitis and atherosclerosis of the brachiocephalic artery (BCA). The changes of the BCA tone were evaluated by ultrasonic duplex scanning before and after transient limb ischemia created by endothelium-dependent vasodilation at baseline and at different laps after the anti-inflammatory and surgical treatment. The size of atherosclerotic plaques before and after the treatment was measured. In the early stages of treatment there were no changes of the tone of the brachial artery. The long-term results after conservative treatment also showed no changes but 6 months after surgical treatment in all patients the study showed the improved of the brachial artery tone on average 3-4% and a slight tendency to decrease of the atherosclerotic plaque. PMID- 27367195 TI - [Sensitivity of microbial associations of periodontal lesions to antibacterial agents]. AB - The aim of the study was the development of approaches to improve the effectiveness of antibiotic therapy in dental practice on the basis of determining the sensitivity of pathogenic microorganisms to antibiotics of different groups. MATERIAL AND METHODS: The study included determination of the sensitivity of the microbial complexes from wound exudate of periodontal pocket and apical abscess to macrolides, quinolones, penicillins, lincosamides and 5 nitroimidazole. A survey of dentists and dental clinics patients to identify the cause and frequency of use of antibiotics and to identify possible adverse reactions was also conducted. RESULTS: Dentists prefer macrolide antibiotics, protected penicillins, and fluoroquinolone combined with 5-nitroimidazole. All patients have taken antibiotics themselves at least once a year. Microbial complexes in patients with acute and exacerbated apical periodontitis in 79% of cases are susceptible to amoxicillin/clavulanic acid, to azithromycin - 52%, lincomycin - 36%, 5-nitroimidazole - 68%, ciprofloxacin - 73.7%. In patients with apical abscess high rates of resistance of microbial complexes to all types of antibiotics was revealed (33% for lincomycin 76,1% for ciprofloxacin, 28,6% for 5 nitroimidazole). Patients with moderate to severe periodontitis in 90.5% are sensitive to amoxicillin/clavulanic acid and azithromycin, in 62.4% to lincomycin. Sensitivity to ciprofloxacin was detected in 85.7% of patients, in 14.3% - moderate resistance. PMID- 27367196 TI - [The use of Foley catheter in reconstructive procedures involving the middle third of the facial skeleton]. AB - The aim of this study was to improve the efficiency of surgical treatment of patients with fractures involving zygomatico-orbital complex and maxillary sinus through the use of Foley catheter. 352 patients with fractures of the middle third of the facial skeleton were treated at the Departments of Oral & Maxillofacial Surgery in Novokuznetsk Institute and I.M. Sechenov First MSMU. All patients underwent open reduction and osteosynthesis using extramedullary titanium mini-plates and NiTi mini-clamps. In the cases with large bone defects additional reconstructive techniques were used such as replantation of bone fragments and endoprosthesis with NiTi implants. For the purpose of drainage and retention Foley catheter was placed in the cavity of the maxillary sinus after the surgical procedure. We obtained good and satisfactory results in the majority of clinical cases. The use of Foley catheter was found to be very effective for the post-operative drainage and hemostasis of the maxillary sinus and in cases involving the use of fixation implant in the reconstructive surgeries in the middle third of the face. PMID- 27367197 TI - [Integrated approach to nasal defects reconstruction]. AB - The aim of the study was to define and solve main problems in nasal defects reconstruction procedures planning. Fifty-two patients with nasal defects treated in Central Research Institute of Dentistry and Maxillofacial Surgery in 2010-2015 were included in the study. In 28 cases the defects were reconstructed by means of paramedial forehead flap. The authors highlight typical procedure pitfalls mainly associated with the planning stage. The study results prove paramedical forehead flap to be the most useful tool for subtotal and total nasal defects reconstruction but meticulous procedure planning is a must for success. PMID- 27367198 TI - [The method of quantitative assessment of dentition aesthetic parameters]. AB - This article describes the formula for calculating the aesthetic index of treatment outcome. The formula was derived on the basis of the obtained regression equations showing the dependence of visual assessment of the value of aesthetic violations. The formula can be used for objective quantitative evaluation of the aesthetics of the teeth when smiling before and after dental treatment. PMID- 27367199 TI - [Treatment of distal occlusion in children]. AB - The aim of the study was to investigate the prevalence of distal occlusion in children of Karaganda region and improvement of orthodonontic appliances treatment methods. Complex dental examination of 1500 children of rural districts of the Karaganda region was carried out. Dental examination showed that 88% of children had dental and facial anomalies. Distal occlusion occured in 42% of children. There is a high prevalence of distal occlusion in pediatric population of Karaganda region rural districts. The use of original orthodontic appliance allowed reducing treatment time by SD=0.5 months and meet the aesthetic requirements of the patients. PMID- 27367200 TI - [Oral health status in children with intellectual disability living in organized groups]. AB - The aim of the study was to assess oral health status in in children with intellectual disability (ID) living in Moscow Orphanage No15. The study involved 91 children aged 12 (39 children) and 15 (52 children). Caries incidence and DMFT index, periodontal disease incidence, OHI-S and PMA index, malocclusions incidence were assessed at baseline examination. Caries incidence in 12 and 15 y.o. was moderate (53.85% and 56.0%, correspondingly), as well as DMFT (2.77+/ 0.52 i 2.94+/-0.53 correspondingly). In 2 children with rumination syndrome all teeth were affected by caries and these children received dental treatment under general anesthesia 7 times during last 60 months. Periodontal disease incidence in 12 and 15 y.o. was 89.74% i 86.58%, correspondingly with very high OHI-S indicating unsatisfactory oral hygiene. Malocclusions incidence was 95% and 98%, correspondingly. Thus the main oral problem in children with ID is periodontal disease and poor oral hygiene. Differentiated oral hygiene education approach according to children's physical and intellectual abilities should be considered. Children with rumination syndrome should be addressed by neurologist prior to dental treatment which needs more radical approach. PMID- 27367201 TI - [Technical features of intraligamental intraseptal anesthesia]. AB - Based on personal clinical experience the authors provide clinical guidelines for periodontal anesthesia. The by-step protocol for intraligamentary and intraseptal anesthesia is presented. The basic mistakes in technique and possible complications are described. Recommendations for a local anesthetic choice and dosage for different groups of teeth are given. PMID- 27367202 TI - Are Four Simple Questions Able to Predict Weight Loss in Outpatients With Metastatic Cancer? A Prospective Cohort Study Assessing the Simplified Nutritional Appetite Questionnaire. AB - BACKGROUND: Severe weight loss is directly responsible for up to one-fifth of all cancer deaths and has a major impact on quality of life. The simplified nutritional appetite questionnaire (SNAQ) was validated to predict weight loss within 6 mo in community-dwelling adults and nursing home residents. METHODS: We prospectively assessed the SNAQ in 133 palliative cancer outpatients. The SNAQ predictions were validated after 3 and 6 mo with the observed weight change. In addition, the treating oncologists gave their predictions concerning future weight loss according to their clinical judgment. RESULTS: A significant weight loss of 5% of the original body weight within 6 mo occurred in 20 (24%) of the 133 patients. The SNAQ predicted weight loss with a sensitivity of 0.38 and a specificity of 0.66 (P-value 0.81). The treating oncologists predicted weight loss with a sensitivity of 0.67 and a specificity of 0.7 (P-value 0.002). CONCLUSION: The SNAQ does not represent a useful tool to predict impending weight loss in palliative cancer outpatients. The predictions of the treating oncologists were more reliable than those from the SNAQ, but remain poor. Better methods to predict weight loss in this patient group are therefore required. PMID- 27367203 TI - A close insight to factor VIII inhibitor in the congenital hemophilia A. AB - INTRODUCTION: Hemophilia A (HA) has an X-linked pattern of inheritance and is the most common of the hemorrhagic disorders. HA is caused by a decreased or deficiency of the functional clotting factor VIII (FVIII) and effects 1 in 5000 10,000 male births. The common treatment for hemophilia is replacement therapy by plasma-derived or recombinant FVIII. Approximately 20-30% of people with a severe type of HA develop an inhibitor and this phenomenon is the main challenge in the management of these patients. Genetic factors and environmental determinants contribute to inhibitor development. Here, the roles of various genetic and environmental factors such as the type of FVIII concentrate used, the number of exposure days, and peak treatment time will be discussed in detail. It seems this information is helpful for hematologists. AREAS COVERED: A literature review was done in January 2016 on PubMed and Scopus using the following keywords:' h(a)emophilia A & factor VIII inhibitor', 'h(a)emophilia A & factor VIII alloantibody', 'h(a)emophilia A & inhibitor'. There was no time limitation; however, there was an English language limitation placed on the articles selected. Expert commentary: Influential genetic and environmental factors in developing inhibitors have been discussed. Most of the risk factors are related to previously untreated patients with hemophili. PMID- 27367204 TI - The Varus Osteoarthritic Knee Has No Coronal Contractures in 90 Degrees of Flexion. AB - Medial and lateral coronal soft tissue laxity in 90 degrees of flexion in the varus osteoarthritic (OA) knee at the time of total knee arthroplasty (TKA) is unknown, meaning, key information as to how the flexion gap should be addressed by surgery is not available. The purpose of this study was to define the coronal plane medial and lateral laxity in 90 degrees of flexion in the end-stage OA knee. Computer assisted surgery (CAS) displays and direct joint observations were used to manipulate the knee to its neutral position in 90 degrees of flexion prior to any surgical releases. Laxity was measured as medial and lateral displacement from the neutral axis of the knee and compared with literature values for healthy subjects. The 72 knees examined had a mean varus deformity, measured in maximum extension, of -7.9 +/- 3.1 degrees (-0.5 to -15 degrees). At 90 degrees of flexion, mean medial and lateral laxity as measured by displacement from the neutral axis of the knee was 3.8 +/- 1.4 degrees and 4.7 +/- 2 degrees respectively. This medial laxity was significantly greater -1.7 degrees (95% CI, 3.1 to -0.3 degrees) than that seen in healthy knees (p < 0.0001) whereas the measured lateral laxity displayed a nonsignificant difference compared with healthy knees. The mean difference in medial-lateral laxity was 1.5 +/- 1.1 degrees. A medial-lateral difference of <=2.5 degrees was present in 91.6% of knees. We found no evidence of contractures in the coronal plane tissue of the end-stage OA knee at the time of TKA. Absolute medial-lateral balance is not typical of the end-stage OA knee in 90 degrees of flexion with a small medial lateral difference typically present. Careful examination of the soft tissues in flexion at the commencement of TKA may help guide surgery to optimize the coronal plane soft tissue envelope. Our findings would suggest that large releases during either a gap-balanced or a measured-resection TKA would not typically be necessary, and that releases that increase laxity in flexion may increase often already lax medial tissue or increase laxity within lateral tissues that typically already have physiological tension. PMID- 27367205 TI - Infections after Anterior Cruciate Ligament Reconstruction: Which Antibiotic after Arthroscopic Debridement? AB - Arthroscopic debridement has proven to be the optimal surgical treatment for infections of the anterior cruciate ligament reconstruction (ACLR). Nevertheless, there are no reported data for the best antibiotic treatment option and its duration. The purpose of this article is to assess the usefulness of oral levofloxacin and rifampicin for the treatment of acute infections of an ACLR. This is a retrospective observational cohort study of patients operated on for ACLR over 4 years. A diagnosis of septic arthritis was based on patients' anamnesis and physical examination, laboratory parameters, and cultures of synovial fluid and/or joint tissue. Arthroscopic lavage was performed as soon as possible and tissue samples were taken. At a minimum 2-year follow-up, the infection was considered cured with a normal C-reactive protein (CRP) level and a correctly functioning and pain-free knee. Of the 810 patients, 15 (1.8%) were diagnosed as having an infection. Among the 13 staphylococcal cases (86.6%), 10 were susceptible to both quinolones and rifampicin (76.9% of the staphylococcal infections). There were two staphylococci that were rifampicin resistant. In the remaining one case, the coagulase-negative staphylococcus (CNS) was resistant to quinolones. One CNS infection was treated with linezolid and rifampicin and was the only case that needed graft removal due to treatment failure. Antibiotic treatment lasted an average of 6 weeks and oral treatment started at a mean of 5 days (range, 4-7). In the remaining 12 patients, CRP levels returned to normal at a mean of 3 weeks with good knee function and no local symptoms. Staphylococci (especially CNS) are responsible for almost 90% of acute ACLR infections in the current series. For the first time, the combination of levofloxacin and rifampicin is being proposed as a treatment in cases of an acute staphylococcal infection of an ACLR. An early switch to oral antibiotic treatment (as soon as the cultures are available) with both levofloxacin and rifampicin for a total (empiric and directed) period of 6 weeks should be considered as treatment of choice in acute staphylococcal infections of the ACLR with a retained graft. The level of evidence is IV (case series). PMID- 27367206 TI - Intraobserver and Interobserver Agreement of Magnetic Resonance Imaging for Reparability of Peripheral Meniscal Tears: What Criteria Really Matter? AB - The objective of the study was the determination of the intra- and interobserver agreement of three magnetic resonance imaging (MRI) criteria for reparability: a peripheral rim smaller than 4 mm, a tear longer than 10 mm, and homogenous aspect of meniscal tissue. In two rounds with an interval of at least 6 weeks, three orthopedic surgeons and three musculoskeletal radiologists studied the preoperative MRI scans of 63 patients with a longitudinal full-thickness medial or lateral meniscal tear. All patients had an arthroscopic meniscal repair. The blinded images were evaluated measuring the tear length and rim width and meniscal aspect was classified. Agreement was calculated using the linear weighted kappa coefficient (kappa) and the intraclass correlation coefficient (ICC). Examiner agreement strength was defined according to the guidelines of Landis and Koch. Intraobserver agreement was poor to good (kappa, 0.12-0.72) for the classification of the meniscal aspect and decreased in lateral meniscal tears. The interobserver agreement for meniscal aspect was mainly poor to fair (kappa, 0.09-0.53). The intraobserver reliability for measurement of the length of the meniscal tear was moderate to excellent (ICC, 0.51-0.80) for all observers in both rounds and moderate to good (ICC, 0.59-0.73) for measurement of the peripheral rim width. The interobserver agreement on tear length and rim width was moderate in both rounds (ICC, 0.58 and 0.50 in round 1; 0.50 and 0.50 in round 2, respectively). Tear length and rim width are the only two measurements with moderate to good agreement. However, these measurements do not predict reparability of longitudinal meniscal tears on MRI images. PMID- 27367208 TI - Editorial. PMID- 27367207 TI - Prognostic significance of signal transducer and activator of transcription 5 and 5b expression in Epstein-Barr virus-positive patients with chronic lymphocytic leukemia. AB - Signal transducer and activator of transcription (STAT) proteins have been intensively studied in hematologic malignancies, and the efficacy of agents against STATs in lymphomas is already under research. We investigated the expression of total STAT5 and STAT5b in peripheral blood samples of patients with chronic lymphocytic leukemia (CLL) in correlation with the presence of Epstein Barr Virus (EBV) and its major oncoprotein (latent membrane protein 1, LMP1). The EBV load was measured in the peripheral blood by real-time PCR for the BXLF1 gene and the levels of LMP1 by PCR and ELISA. Western blotting was performed for total STAT5 and STAT5b in protein extracts. STAT5b was only expressed in patients (not in healthy subjects) and STAT5 but particularly STAT5b expression was correlated with the presence of the virus (77.3% vs. 51.2%, P = 0.006 for STAT5b) and to the expression of LMP1 (58.3% vs. 21.6%, P = 0.011 for STAT5b). Moreover, the expression of STAT5b and the presence of EBV and LMP1 were strongly negatively correlated with the overall survival of the patients (log-rank test P = 0.011, 0.015, 0.006, respectively). Double positive (for EBV and STAT5b) patients had the lowest overall survival (log-rank test P = 0.013). This is the first report of a survival disadvantage of EBV+ patients with CLL, and the first time that STAT5b expression is correlated with survival. The correlation of STAT5 expression with the presence of the virus, along with our survival correlations defines a subgroup of patients with CLL that may benefit from anti-STAT agents. PMID- 27367209 TI - Effect of folic acid on oxidative stress and behavioral changes in the animal model of schizophrenia induced by ketamine. AB - Recent studies have shown benefits for the supplementation of folic acid in schizophrenic patients. The aim of this study was to evaluate the effects of folic acid addition on adult rats, over a period of 7 or 14 days. It also sets out to verify any potential protective action using an animal model of schizophrenia induced by ketamine, in behavioral and biochemical parameters. This study used two protocols (acute and chronic) for the administration of ketamine at a dose of 25 mg/kg (i.p.). The folic acid was given by oral route in doses of 5, 10 and 50 mg/kg, once daily, for 7 and/or 14 days in order to compare the protective effects of folic acid. Thirty minutes after the last administration of ketamine, the locomotor and social interaction activities were evaluated, and immediately the brain structure were removed for biochemical analysis. In this study, ketamine was administered in a single dose or in doses over the course of 7 days increasing the animal's locomotion. This study showed that the administration of folic acid over 7 days was unable to prevent hyper locomotion. In contrast, folic acid (10 and 50 mg/kg) administrated over a period of 14 days, was able to partially prevent the hyper locomotion. Our data indicates that both acute and chronic administrations of ketamine increased the time to first contact between the animals, while the increased latency for social contact was completely prevented by folic acid (5, 10 and 50 mg/kg). Chronic and acute administrations of ketamine also increased lipid peroxidation and protein carbonylation in brain. Folic acid (10 and 50 mg/kg) supplements showed protective effects on the oxidative damage found in the different brain structures evaluated. All together, the results indicate that nutritional supplementation with folic acid provides promising results in an animal model of schizophrenia induced by ketamine. PMID- 27367211 TI - FROM THE ADAA PRESIDENT. PMID- 27367210 TI - Testing different paradigms to optimize antidepressant deep brain stimulation in different rat models of depression. AB - Deep brain stimulation (DBS) of several targets induces beneficial responses in approximately 60% of patients suffering from treatment-resistant depression (TRD). The remaining 40% indicate that these stimulation sites do not bear therapeutic relevance for all TRD patients and consequently DBS-targets should be selected according to individual symptom profiles. We here used two animal models of depression known to have different genetic backgrounds and behavioral responses: the therapy-responsive Flinders sensitive line (FSL) and the therapy refractory congenitally learned helpless rats (cLH) to study symptom-specific DBS effects i) of different brain sites ii) at different stimulation parameters, and iii) at different expressions of the disease. Sham-stimulation/DBS was applied chronic-intermittently or chronic-continuously to either the ventromedial prefrontal cortex (vmPFC, rodent equivalent to subgenual cingulate), nucleus accumbens (Nacc) or subthalamic nucleus (STN), and effects were studied on different depression-associated behaviors, i.e. anhedonia, immobility/behavioral despair and learned helplessness. Biochemical substrates of behaviorally effective versus ineffective DBS were analyzed using in-vivo microdialysis and post-mortem high-performance liquid chromatography (HPLC). We found that i) vmPFC DBS outperforms Nacc-DBS, ii) STN-DBS increases depressive states, iii) chronic continuous DBS does not add benefits compared to chronic-intermittent DBS, iv) DBS-efficacy depends on the disease expression modeled and iv) antidepressant DBS is associated with an increase in serotonin turnover alongside site-specific reductions in serotonin contents. The reported limited effectiveness of vmPFC DBS suggests that future research may consider the specific disease expression, investigation of different DBS-targets and alternative parameter settings. PMID- 27367212 TI - A Simple and Powerful Risk-Adjustment Tool for 30-day Mortality Among Inpatients. AB - BACKGROUND: Risk adjustment for mortality is increasingly important in an era when hospitals and health care systems are being compared with respect to health outcomes and quality. A powerful predictive model has been developed to risk adjust for 30-day mortality among inpatients, but it is complex and not widely used. OBJECTIVE: To develop and validate a simpler model, with predictive power similar to more complex models. RESEARCH DESIGN: This was a retrospective split validation study. In a derivation cohort, a predictive model for 30-day mortality was developed using logistic regression with the Charlson comorbidity score, Laboratory-Based Acute Physiology Score, and age as the predictor variables. In the validation cohort, the performance and calibration of the model to predict 30 day mortality was examined. SUBJECTS: All admissions to the medical service of 2 urban university-based teaching hospitals located in Bronx, New York, between July 1, 2002, and April 30, 2008. MEASURES: All-cause mortality was taken from the social security death registry. Predictor variables were constructed from demographic characteristics, laboratory and billing data extracted from a clinical data repository. RESULTS: The study sample included 147 991 admissions and overall 30-day mortality was 5.4%. The model had excellent discrimination, with a c-statistics of 0.8585 in the derivation cohort and 0.8484 in the validation cohort. The model accurately predicts 30-day mortality in all risk deciles. CONCLUSIONS: This simple and powerful predictive model can be used by hospitals and health care systems as a risk-adjustment tool for quality and research purposes. PMID- 27367213 TI - Impact of the Hospital to Home Initiative on Readmissions in the VA Health Care System. AB - BACKGROUND: Hospital to Home (H2H) is a national quality improvement initiative sponsored by the Institute for Healthcare Improvement and the American College of Cardiology, with the goal of reducing readmission for patients hospitalized with heart disease. We sought to determine the impact of H2H within the Veterans Affairs (VA) health care system. METHODS: Using a controlled interrupted time series, we determined the association of VA hospital enrollment in H2H with the primary outcome of 30-day all-cause readmission following a heart failure hospitalization. VA heart failure providers were surveyed to determine quality improvement projects initiated in response to H2H. Secondary outcomes included initiation of recommended H2H projects, follow-up within 7 days, and total hospital days at 30 days and 1 year. RESULTS: Sixty-five of 104 VA hospitals (66%) enrolled in the national H2H initiative. Hospital characteristic associated with H2H enrollment included provision of tertiary care, academic affiliation, and greater use of home monitoring. There was no significant difference in mean 30-day readmission rates (20.0% +/- 5.0% for H2H vs 19.3% +/- 5.9% for non-H2H hospitals; P = .48) The mean fraction of patients with a cardiology visit within 7 days was slightly higher for H2H hospitals (3.0% +/- 2.4% for H2H vs 2.0% +/- 1.9% for non-H2H hospitals; P = .05). Patients discharged from H2H hospitals had fewer mean hospitals days during the following year (7.6% +/- 2.6% for H2H vs 9.2% +/- 3.0 for non-H2H; P = .01) early after launch of H2H, but the effect did not persist. CONCLUSIONS: VA hospitals enrolling in H2H had slightly more early follow-up in cardiology clinic but no difference in 30-day readmission rates compared with hospitals not enrolling in H2H. PMID- 27367214 TI - Layout Improvement Study to Reduce Staff Walking Distance in a Large Health Care Facility: How to Not Walk an Extra 4740 Miles. AB - Inefficient facility layouts have been found to be a challenge in health care, with excessive walking adding to the demands of staff and creating delays, which can impact the quality of care. Minimizing unnecessary transportation during care delivery improves efficiency, reduces delays, and frees up resources for use on value-added activities. This article presents a methodology and application of facility design to improve responsiveness and efficiency at a large hospital. The approach described provides the opportunity to improve existing layouts in facilities in which the floor plan is already defined, but there is some flexibility to relocate key areas. The existing physical constraints and work flows are studied and taken into consideration, and the volume of traffic flow throughout the facility guides the decision of where to relocate areas for maximum efficiency. Details on the steps followed and general recommendations to perform the necessary process and data analyses are provided. We achieved a 34.8% reduction in distance walked (4740 miles saved per year) and a 30% reduction in floors traveled in elevators (344 931 floors, which translate to 842 hours spent using elevators) by relocating 4 areas in which frequently used resources are housed. PMID- 27367215 TI - The Impact of Cross-Unit Coordination and Process Improvement Efforts in Anatomic Pathology: A Systems Perspective. AB - BACKGROUND: The impact of coordination and problem solving on health care quality has become increasingly prevalent within the literature. However, few studies have empirically investigated the impact of these factors across organizational boundaries. METHODS: This was an embedded, single-case study conducted within a large, academic Anatomic Pathology department. We surveyed 96 team members within 18 distinct processing or specialty units within the department and forward the Network Alignment Approach to measure coordination between units. In addition, we measure perceived safety culture and frequency of error in specimen documentation and preparation. RESULTS: Regression results suggest that downstream cross-unit coordination between units (clarity of customer requirements) significantly improves safety culture (P < .001). In addition, within-unit process improvement efforts improved safety culture (P < .001). These 2 factors alone accounted for 30% of the variation in the regression model, with safety culture as our dependent variable. CONCLUSION: Clarity of customer requirements and process improvement efforts significantly improve safety culture within the system. This approach to understanding and analyzing connections within complex systems provides insight into specific ways that leaders can begin to understand how each unit or department can improve as both a customer and a supplier within the larger system. PMID- 27367217 TI - What Factors Influence Employee Service Recovery Performance and What Are the Consequences in Health Care? AB - OBJECTIVES: We analyzed the extent to which the service recovery performance of frontline employees in private health care institutions is influenced by employee perceptions of manager attitudes toward service quality, workplace support, and manager fairness and organizational commitment. We also examined the relationship of service recovery performance to employee job satisfaction and turnover intentions. METHODS: Partial least square path modeling of data from 178 frontline employees in private health care institutions in North Cyprus was utilized. RESULTS: Although empowerment and role clarity were positively related to service recovery performance, perceived managerial attitudes toward hospital customer service, teamwork, and customer service-oriented training as indicators of workplace support were not related to frontline employees' service recovery performance. Organizational justice was related to affective commitment, which in turn was related to service recovery performance. Although service recovery performance was not related to employee turnover intentions, it was related to job satisfaction. CONCLUSION: Managerial implications of these study findings are presented in the light of the cognitive evaluation theory. Health services differ from other service organizations in the way that intrinsic and extrinsic rewards influence the service recovery efforts of frontline employees. To ensure high quality services, managers should focus on intrinsic rewards, empower and give more autonomy to staff. PMID- 27367216 TI - Testing the Quality Health Outcomes Model Applied to Infection Prevention in Hospitals. AB - OBJECTIVE: To test the Quality Health Outcomes Model to investigate the relationship between health care-associated infection (HAI) prevention interventions, organizational context, and HAI outcomes using structural equation modeling. METHODS: Variables for adherence to the central line bundle, organizational context, and central line-associated bloodstream infections (CLABSIs) were selected for this secondary data analysis from 614 US hospitals that participated in the Prevention of Nosocomial Infection and Cost effectiveness-Refined study. One half of the dataset was used for exploration of the concepts, the second half for confirmation of the measurement models and testing of the structural model. RESULTS: The final model resulted in a good fit to the data (chi (1215) = 1906.86, P < .00; comparative fit index = 0.94; root mean square of error of approximation = 0.04). A significant relationship was noted between adherence to the central line bundle interventions and organizational context (beta = 0.23, P < .01), whereas the relationship between context and CLABSIs was not significant (beta = -0.20, P = .78). CONCLUSIONS: This study supports a relationship between greater adherence to HAI interventions and higher levels of organizational context and highlights the complexity of measuring organizational context. Given the importance of preventing HAIs, ongoing research is needed to reveal the exact aspects of context that influence interventions and outcomes. PMID- 27367218 TI - Shared Medical Appointments: Impact on Clinical and Quality Outcomes in Veterans With Diabetes. AB - Managing diabetes poses substantial challenges to the over 29.1 million Americans afflicted, and is financially overwhelming to the US health care system. One potential strategy is utilizing a group approach to care delivery or shared medical appointment (SMA). The purpose of this 3-year retrospective VA study was to investigate differences in clinical and quality outcome measures in veterans with type 2 diabetes who used SMAs and those who received only usual care (UC) one-on-one with their doctor. This observational, 2-group cohort study used abstracted medical records from a large Midwestern Veterans Administration hospital. Clinical outcome metrics included hemoglobin A1c (hbA1c), systolic blood pressure, low-density lipoprotein cholesterol, and emergency department (ED) visits. Quality outcomes included Veterans' Administration (VA) Department of Defense clinical practice guidelines for the management of diabetes. A total of 988 total VA cases were examined retrospectively over 3 years: 371 cases had used SMAs and 617 were in the UC cohort, and had never attended a diabetes SMA. The study period used abstracted VA medical records from 2008 to 2010. There were no statistically significant differences in HbA1c, systolic blood pressure, and ED visits between groups; however, hbA1c for individuals who attended SMAs was 8.55 (standard deviation [SD] = 1.72) and UC was 7.49 (SD = 1.28) (P < .001). All clinical outcomes were worse at baseline for the SMA cohort. UC had mean ED visits/3 years (mean = 18.62, SD = 13.53, P < .001) versus SMA participants (mean = 27.97, SD = 14.00, P <. 001), revealing a propensity for high health care utilization. SMA providers had statistically significant differences over UC cases on quality measures, including ordering annual ophthalmology and podiatry examinations (P < .001) and prescribing aspirin and angiotension-converting enzyme inhibitors (ACE-I). SMAs may provide a venue for assessing and delivering quality care for patients with type 2 diabetes. More research is needed to ascertain effective strategies for diabetes disease management in high-risk patients. PMID- 27367219 TI - Effectiveness of Shared Medical Appointments Versus Traditional Clinic Visits for Adolescents With Type 1 Diabetes. AB - Shared medical appointments began in the United States in 1996 to advance quality of care and enhance patients' ability to self-manage. Group visits gather patients with the same diagnosis for individual examinations followed by group education sessions taught by the provider. This leads to the opportunity to learn from the experiences of others. The Cleveland Clinic Department of Pediatric Endocrinology offers a shared medical appointment group for pediatric patients with type 1 diabetes called the ESCALAIT clinic (Enrichment Services and Care for Adolescents Living with Autoimmune Insulin Dependent Type 1 Diabetes). The objective of this study was to compare the effectiveness of traditional clinic visits with shared medical appointments for adolescents with type 1 diabetes in terms of hemoglobin A1c (HbA1c) improvement. Eighty ESCALAIT patients, aged 11 to 19 years were compared with 516 clinic controls of the same age. Visits were approximately 3 months apart for both patient groups. Changes in HbA1c between groups were calculated from the first to fourth visits. There was a statistically significant difference between the ESCALAIT clinic patients and the control patients. Our results revealed that the group visit patients had less improvement in HbA1c values at the last visit approximately 1 year later, but we would argue that the difference is not clinically significant. However, there were many benefits to shared medical appointment visits including increased access to care as well as peer support. Shared medical appointments are therefore a valid alternative to traditional clinic visits in this patient population. PMID- 27367220 TI - Toward Eliminating All Harms. PMID- 27367221 TI - Factors Associated With Reintubation in Patients With Chronic Obstructive Pulmonary Disease. PMID- 27367222 TI - Response to a Letter to the Editor. PMID- 27367226 TI - Avoiding the Unintended Consequences of Screening for Social Determinants of Health. PMID- 27367228 TI - Eradicating the grey squirrel Sciurus carolinensis from urban areas: an innovative decision-making approach based on lessons learnt in Italy. AB - BACKGROUND: Eradication of invasive alien species supports the recovery of native biodiversity. A new European Union Regulation introduces obligations to eradicate the most harmful invasive species. However, eradications of charismatic mammals may encounter strong opposition. Considering the case study of the eastern grey squirrel (Sciurus carolinensis Gmelin, 1788) in central Italy, we developed a structured decision-making technique based on a Bayesian decision network model and explicitly considering the plurality of environmental values of invasive species management to reduce potential social conflicts. RESULTS: The model identified priority areas for management activities. These areas corresponded to the core of the grey squirrel range, but they also included peripheral zones, where rapid eradication is fundamental to prevent the spread of squirrels. However, when the model was expanded to integrate the attitude of citizens towards the project, the intervention strategy slightly changed. In some areas, the citizens' support was limited, and this resulted in a reduced overall utility of intervention. CONCLUSION: The suggested approach extends the scientific basis for management decisions, evaluated in terms of technical efficiency, feasibility and social impact. Here, the Bayesian decision network model analysed the potential technical and social consequences of management actions, and it responded to the need for transparency in the decision-making process, but it can easily be extended to consider further issues that are common in many mammal eradication programmes. Owing to its flexibility and comprehensiveness, it provides an innovative example of how to plan rapid eradication or control activities, as required by the new EU Regulation. (c) 2016 Society of Chemical Industry. PMID- 27367227 TI - Differential Regulation of Duplicate Light-Dependent Protochlorophyllide Oxidoreductases in the Diatom Phaeodactylum tricornutum. AB - BACKGROUND: Diatoms (Bacilliariophyceae) encode two light-dependent protochlorophyllide oxidoreductases (POR1 and POR2) that catalyze the penultimate step of chlorophyll biosynthesis in the light. Algae live in dynamic environments whose changing light levels induce photoacclimative metabolic shifts, including altered cellular chlorophyll levels. We hypothesized that the two POR proteins may be differentially adaptive under varying light conditions. Using the diatom Phaeodactylum tricornutum as a test system, differences in POR protein abundance and por gene expression were examined when this organism was grown on an alternating light:dark cycles at different irradiances; exposed to continuous light; and challenged by a significant decrease in light availability. RESULTS: For cultures maintained on a 12h light: 12h dark photoperiod at 200MUE m-2 s-1 (200L/D), both por genes were up-regulated during the light and down-regulated in the dark, though por1 transcript abundance rose and fell earlier than that of por2. Little concordance occurred between por1 mRNA and POR1 protein abundance. In contrast, por2 mRNA and POR2 protein abundances followed similar diurnal patterns. When 200L/D P. tricornutum cultures were transferred to continuous light (200L/L), the diurnal regulatory pattern of por1 mRNA abundance but not of por2 was disrupted, and POR1 but not POR2 protein abundance dropped steeply. Under 1200MUE m-2 s-1 (1200L/D), both por1 mRNA and POR1 protein abundance displayed diurnal oscillations. A compromised diel por2 mRNA response under 1200L/D did not impact the oscillation in POR2 abundance. When cells grown at 1200L/D were then shifted to 50MUE m-2 s-1 (50L/D), por1 and por2 mRNA levels decreased swiftly but briefly upon light reduction. Thereafter, POR1 but not POR2 protein levels rose significantly in response to this light stepdown. CONCLUSION: Given the sensitivity of diatom por1/POR1 to real-time light cues and adherence of por2/POR2 regulation to the diurnal cycle, we suggest that POR1 supports photoacclimation, whereas POR2 is the workhorse for daily chlorophyll synthesis. PMID- 27367229 TI - Head and Neck Non-Melanoma Skin Cancer Treated By Superficial X-Ray Therapy: An Analysis of 1021 Cases. AB - INTRODUCTION: To report a single-institutional experience with the use of Superficial X-Ray Therapy (SXRT) for head and neck non-melanoma skin cancer (N MSC) and to compare outcomes by prescribed fractionation schedules. MATERIALS AND METHODS: The medical records of 597 patients with 1021 lesions (720 BCC, 242 SCC, 59 SCC in situ) treated with kilovoltage radiation from 1979-2013 were retrospectively reviewed. The majority of patients were treated according to 1 of 3 institutional protocols based on the discretion of the radiation oncologist: 1) 22 x 2.5 Gy; 2) 20 x 2.5 Gy; 3) 30 x 2.0 Gy. "T" stage at first presentation was as follows: Tis (59); T1 (765); T2 (175); T3 (6), T4 (9); Tx, (7). All patients were clinical N0 and M0 at presentation. Chi-square test was used to evaluate any potential association between variables. The Kaplan-Meier method was used to analyze survival with the Log Rank test used for comparison. A Cox Regression analysis was performed for multivariate analysis. RESULTS: The median follow up was 44 months. No significant difference was observed among the 3 prescribed fractionation schemes (p = 0.78) in terms of RTOG toxicity. There were no failures among SCC in situ, 37 local failures (23 BCC, 14 SCC), 5 regional failures (all SCC) and 2 distant failures (both SCC). For BCC, the 5-year LC was 96% and the 10-year LC was 94%. For SCC the corresponding rates of local control were 92% and 87%, respectively (p = 0.03). The use of >2.0 Gy daily was significantly associated with improved LC on multivariate analysis (HR: 0.17; CI 95%: 0.05-0.59). CONCLUSION: SXRT for N-MSC of the head and neck is well tolerated, achieves excellent local control, and should continue to be recommended in the management of this disease. Fractionation schedules using >2.0 Gy daily appear to be associated with improved LC. PMID- 27367230 TI - How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections? AB - Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements. PMID- 27367231 TI - Can, Want and Try: Parents' Viewpoints Regarding the Participation of Their Child with an Acquired Brain Injury. AB - BACKGROUND: Acquired brain injury (ABI) is a leading cause of permanent disability, currently affecting 20,000 Australian children. Community participation is essential for childhood development and enjoyment, yet children with ABI can often experience barriers to participation. The factors which act as barriers and facilitators to community participation for children with an ABI are not well understood. AIM: To identify the viewpoints of parents of children with an ABI, regarding the barriers and facilitators most pertinent to community participation for their child. METHODS: Using Q-method, 41 parents of children with moderate/severe ABI sorted 37 statements regarding barriers and facilitators to community participation. Factor analysis identified three viewpoints. RESULTS: This study identified three distinct viewpoints, with the perceived ability to participate decreasing with a stepwise trend from parents who felt their child and family "can" participate in viewpoint one, to "want" in viewpoint two and "try" in viewpoint three. CONCLUSIONS: Findings indicated good participation outcomes for most children and families, however some families who were motivated to participate experienced significant barriers. The most significant facilitators included child motivation, supportive relationships from immediate family and friends, and supportive community attitudes. The lack of supportive relationships and attitudes was perceived as a fundamental barrier to community participation. SIGNIFICANCE: This research begins to address the paucity of information regarding those factors that impact upon the participation of children with an ABI in Australia. Findings have implications for therapists, service providers and community organisations. PMID- 27367232 TI - Systematic comparative content analysis of 17 psychosocial work environment questionnaires using a new taxonomy. AB - BACKGROUND: Many questionnaires have been developed to measure how psychosocial characteristics are perceived in a work environment. But the content validity of these questionnaires has rarely been questioned due to the absence of a reference taxonomy for characteristics of work environments. OBJECTIVES: To propose an exhaustive taxonomy of work environment characteristics involved in psychosocial risks and to apply this taxonomy to questionnaires on workplace psychosocial factors. METHODS: The taxonomy was developed by categorizing factors present in the main theoretical models of the field. Questionnaire items most frequently cited in scientific literature were retained for classification. RESULTS: The taxonomy was structured into four hierarchical levels and comprises 53 categories. The 17 questionnaires analyzed included 927 items: 59 from the "physical environment" category, 116 from the "social environment" category, 236 from the "work activity" category, 255 from the "activity management" category, and 174 from the "organizational context" category. CONCLUSIONS: There are major content differences among analyzed questionnaires. This study offers a means for selecting a scale on the basis of content. PMID- 27367233 TI - Effect of Intravenous Mannitol on Intraocular Pressure in Vitrectomized Silicone Oil-Filled Eyes. AB - PURPOSE: To evaluate the effect of intravenous mannitol (IVM) on intraocular pressure (IOP) in vitrectomized eyes. METHODS: Thirty-one patients with raised IOP after retinal surgery with silicone oil injection were included. Patients were administered IVM (20% solution, 1g/Kg, over 30 minutes) and IOP was noted at regular intervals. IOP reduction in vitrectomized eyes (Group 1) was compared with the normal eyes (Group 2). RESULT: Percentage IOP reduction was higher in Group 1 than in Group 2 at all time intervals, 24.5% vs. 19.2% at 15 minutes (p=0.34), 22.6% vs. 9.8% at 45 minutes (p=0.003), 19.1% vs. 9.9% at two hours (p=0.023), and 16.1% vs. 7.8% at four hours (p=0.04), respectively. In Group 1, 40% eyes had an IOP reduction of 2-6 mmHg while 30% eyes had IOP reduction >6 mmHg at four hours post-IVM. CONCLUSION: IVM is useful for short-term IOP reduction in vitrectomized eyes. IOP reduction is independent of baseline IOP, and sustained and higher as compared to normal eyes. PMID- 27367234 TI - NSAIDs and EGFR Inhibitors for Duodenal Polyp Prevention. PMID- 27367235 TI - Discovery of additional brain metastases on the day of stereotactic radiosurgery: risk factors and outcomes. AB - OBJECTIVE High-resolution double-dose gadolinium-enhanced Gamma Knife (GK) radiosurgery-planning MRI (GK MRI) on the day of GK treatment can detect additional brain metastases undiagnosed on the prior diagnostic MRI scan (dMRI), revealing increased intracranial disease burden on the day of radiosurgery, and potentially necessitating a reevaluation of appropriate management. The authors identified factors associated with detecting additional metastases on GK MRI and investigated the relationship between detection of additional metastases and postradiosurgery patient outcomes. METHODS The authors identified 326 patients who received GK radiosurgery at their institution from 2010 through 2013 and had a prior dMRI available for comparison of numbers of brain metastases. Factors predictive of additional brain metastases on GK MRI were investigated using logistic regression analysis. Overall survival was estimated by Kaplan-Meier method, and postradiosurgery distant intracranial failure was estimated by cumulative incidence measures. Multivariable Cox proportional hazards model and Fine-Gray regression modeling assessed potential risk factors of overall survival and distant intracranial failure, respectively. RESULTS The mean numbers of brain metastases (SD) on dMRI and GK MRI were 3.4 (4.2) and 5.8 (7.7), respectively, and additional brain metastases were found on GK MRI in 48.9% of patients. Frequencies of detecting additional metastases for patients with 1, 2, 3-4, and more than 4 brain metastases on dMRI were 29.5%, 47.9%, 55.9%, and 79.4%, respectively (p < 0.001). An index brain metastasis with a diameter greater than 1 cm on dMRI was inversely associated with detecting additional brain metastases, with an adjusted odds ratio of 0.57 (95% CI 0.4-0.9, p = 0.02). The median time between dMRI and GK MRI was 22 days (range 1-88 days), and time between scans was not associated with detecting additional metastases. Patients with additional brain metastases did not have larger total radiosurgery target volumes, and they rarely had an immediate change in management (abortion of radiosurgery or addition of whole-brain radiation therapy) due to detection of additional metastases. Patients with additional metastases had a higher incidence of distant intracranial failure than those without additional metastases (p = 0.004), with an adjusted subdistribution hazard ratio of 1.4 (95% CI 1.0-2.0, p = 0.04). Significantly worse overall survival was not detected for patients with additional brain metastases on GK MRI (log-rank p = 0.07), with the relative adjusted hazard ratio of 1.07, (95% CI 0.81-1.41, p = 0.65). CONCLUSIONS Detecting additional brain metastases on GK MRI is strongly associated with the number of brain metastases on dMRI and inversely associated with the size of the index brain metastasis. The discovery of additional brain metastases at time of GK radiosurgery is very unlikely to lead to aborting radiosurgery but is associated with a higher incidence of distant intracranial failure. However, there is not a significant difference in survival. ? CLASSIFICATION OF EVIDENCE Type of question: prognostic; study design: retrospective cohort trial; evidence: Class IV. PMID- 27367237 TI - Nonrandom spatial clustering of spontaneous anterior fossa cerebrospinal fluid fistulas and predilection for the posterior cribriform plate. AB - OBJECTIVE The anterior skull base is a common site for the spontaneous development of meningoceles, encephaloceles, and meningoencephaloceles that can lead to cerebrospinal fluid (CSF) fistula formation, particularly in association with idiopathic intracranial hypertension. In some circumstances the lesions are difficult to localize. Whether all sites in the anterior skull base are equally prone to fistula formation or whether they are distributed randomly throughout the anterior skull base is unknown, although the anterior cribriform plate has been proposed as the most frequent location. The purpose of this study was to identify sites of predilection in order to provide assistance for clinicians in finding occult leaks and increase the understanding of the etiology of this pathology. METHODS The authors performed a retrospective review of a prospectively acquired surgical database of all endonasal endoscopic surgeries performed at Weill Cornell Medical College by the senior authors. Spontaneous CSF fistulas of the anterior skull base were identified. The anatomical sites of the defects were located on radiographic images and normalized to a theoretical 4 * 2 grid representing the anterior midline skull base. Data from the left and right skull base were combined to increase statistical power. This grid was then used to analyze the distribution of defects. Frequency analysis was performed by means of a chi-square test, with a subsequent Monte Carlo simulation to further strengthen the statistical support of the conclusions. RESULTS Nineteen cases of spontaneous CSF fistulas were identified. Frequency analysis using chi-square indicated a nonrandom distribution of sites (p = 0.035). Monte Carlo simulation supported this conclusion (p = 0.034). Seventy-four percent of cases occurred in the cribriform plate (p = 0.086). Moreover, 37% of all defects occurred in the posterior third of the cribriform plate. CONCLUSIONS Anterior skull base spontaneous CSF leaks are distributed in a nonrandom fashion. The most likely site of origin of the spontaneous CSF leaks of the anterior midline skull base is the cribriform plate, particularly the posterior third of the plate, likely because of the lack of significant thick bony buttressing. Clinicians searching for occult spontaneous leaks of the anterior skull base should examine the cribriform plate, especially the posterior third with particularly close scrutiny. PMID- 27367236 TI - Carotid artery stenosis with a high-intensity signal plaque on time-of-flight magnetic resonance angiography and association with evidence of intraplaque hypoxia. AB - OBJECTIVE Hypoxia induces angiogenesis and plays a major role in the progression of carotid plaques. During carotid intervention, plaques with high-intensity signals on time-of-flight (TOF) magnetic resonance angiography (MRA) often cause ischemic stroke and embolic complications. However, the role of intraplaque hypoxia before carotid endarterectomy (CEA) and carotid artery stenting is not presently understood. In this study the authors aimed to investigate the relationship between intraplaque hypoxia and MRA findings. METHODS Nineteen consecutive patients with 20 carotid artery stenoses who underwent CEA at Saga University Hospital between August 2008 and December 2014 were enrolled in the study. The expressions of hypoxia-inducible transcription factor-1alpha (HIF 1alpha) and vascular endothelial growth factor (VEGF) were analyzed by immunohistochemical analysis. In addition, the relationship between the findings on TOF MRA and pathology for the carotid plaques was analyzed. RESULTS High intensity plaques on TOF MRA showed higher expression levels of HIF-1alpha (p = 0.015) and VEGF (p = 0.007) compared with isointensity plaques. The rate of intraplaque hemorrhage (IPH) on TOF MRA was also significantly higher in the high intensity plaques than in the isointensity plaques (p = 0.024). Finally, the mean number of neovessels was significantly higher in those without plaque hemorrhage than in those with plaque hemorrhage (p = 0.010). CONCLUSIONS Plaques with high intensity signals on TOF MRA were associated with IPH and evidence of intraplaque hypoxia. This fact may represent an opportunity to establish novel therapeutic agents targeting intraplaque hypoxia. PMID- 27367238 TI - Preoperative and postoperative predictors of long-term outcome after endovascular treatment of poor-grade aneurysmal subarachnoid hemorrhage. AB - OBJECTIVE An increasing number of patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) have received endovascular treatment. Endovascular treatment of poor-grade aSAH, however, is based on single-center retrospective studies, and predictors of long-term outcome have not been well defined. Using results from a multicenter prospective registry, the authors aimed to develop preoperative and postoperative prognostic models to predict poor outcome after endovascular treatment of poor-grade aSAH. METHODS A Multicenter Poor-grade Aneurysm Study (AMPAS) was a prospective and observational registry of consecutive patients with poor-grade aSAH. From October 2010 to March 2012, 366 patients were enrolled in the registry, and 136 patients receiving endovascular treatment were included in this study. Outcome was assessed by modified Rankin Scale (mRS) score at 12 months, and poor outcome was defined as an mRS score of 4, 5, or 6. Prognostic models were developed in multivariate logistic regression models. The area under receiver operating characteristic curves (AUC) was used to assess the model's discriminatory ability, and Hosmer-Lemeshow goodness-of-fit tests were used to assess the calibration. RESULTS At 12 months, 64 patients (47.0%) had a poor outcome: 9 (6.6%) had an mRS score of 4, 6 (4.4%) had an mRS score of 5, and 49 (36.0%) had died. Univariate analyses showed that older age (p = 0.001), female sex (p = 0.044), lower Glasgow Coma Scale score (p < 0.001), a World Federation of Neurosurgical Societies (WFNS) grade of V (p < 0.001), higher Fisher grade (p < 0.001), modified Fisher grade (p < 0.001), and wider neck aneurysm (p = 0.026) were associated with a poor outcome. There was a trend toward a worse outcome in patients with anterior communicating artery aneurysms (p = 0.080) and in those with incompletely occluded aneurysms (p = 0.063). After endovascular treatment, the presence of cerebral infarction (p = 0.039), symptomatic vasospasm (p = 0.039), and pneumonia (p = 0.006) were associated with a poor outcome. Multivariate analyses showed that the preoperative prognostic model including age, a WFNS grade of V, modified Fisher grade, and aneurysm neck size had excellent discrimination with an AUC of 0.86 (95% CI 0.80-0.92, p < 0.001), and a postoperative model that included these predictors as well as postoperative pneumonia had excellent discrimination (AUC = 0.87, 95% CI 0.81 0.93, p < 0.001). Both models had good calibration (p = 0.941 and p = 0.653, respectively). CONCLUSIONS Older age, WFNS Grade V, higher modified Fisher grade, wider neck aneurysm, and postoperative pneumonia were independent predictors of poor outcome after endovascular treatment of poor-grade aSAH. The preoperative model had almost the same discrimination as the postoperative model. Endovascular treatment should be carefully considered in patients with poor-grade aSAH with ruptured wide-neck aneurysms. ? CLASSIFICATION OF EVIDENCE Type of question: prognostic; study design: retrospective cohort trial; evidence: Class I. PMID- 27367239 TI - Letter to the Editor: The bispectral index is a dimensionless number. PMID- 27367240 TI - Resection and brain brachytherapy with permanent iodine-125 sources for brain metastasis. AB - OBJECTIVE Stereotactic radiosurgery (SRS) with or without whole-brain radiotherapy can be used to achieve local control (> 90%) for small brain metastases after resection. However, many brain metastases are unsuitable for SRS because of their size or previous treatment, and whole-brain radiotherapy is associated with significant neurocognitive morbidity. The purpose of this study was to investigate the efficacy and toxicity of surgery and iodine-125 (125I) brachytherapy for brain metastases. METHODS A total of 95 consecutive patients treated for 105 brain metastases at a single institution between September 1997 and July 2013 were identified for this analysis retrospectively. Each patient underwent MRI followed by craniotomy with resection of metastasis and placement of 125I sources as permanent implants. The patients were followed with serial surveillance MRIs. The relationships among local control, overall survival, and necrosis were estimated by using the Kaplan-Meier method and compared with results of log-rank tests and multivariate regression models. RESULTS The median age at surgery was 59 years (range 29.9-81.6 years), 53% of the lesions had been treated previously, and the median preoperative metastasis volume was 13.5 cm3 (range 0.21-76.2 cm3). Gross-total resection was achieved in 81% of the cases. The median number of 125I sources implanted per cavity was 28 (range 4-93), and the median activity was 0.73 mCi (range 0.34-1.3 mCi) per source. A total of 476 brain MRIs were analyzed (median MRIs per patient 3; range 0-22). Metastasis size was the strongest predictor of cavity volume and shrinkage (p < 0.0001). Multivariable regression modeling failed to predict the likelihood of local progression or necrosis according to metastasis volume, cavity volume, or the rate of cavity remodeling regardless of source activity or previous SRS. The median clinical follow-up time in living patients was 14.4 months (range 0.02 13.6 years), and crude local control was 90%. Median overall survival extended from 2.1 months in the shortest quartile to 62.3 months in the longest quartile (p < 0.0001). The overall risk of necrosis was 15% and increased significantly for lesions with a history of previous SRS (p < 0.05). CONCLUSIONS Therapeutic options for patients with large or recurrent brain metastases are limited. Data from this study suggest that resection with permanent 125I brachytherapy is an effective strategy for achieving local control of brain metastasis. Although metastasis volume significantly influences resection cavity size and remodeling, volumetric parameters do not seem to influence local control or necrosis. With careful patient selection, this treatment regimen is associated with minimal toxicity and can result in long-term survival for some patients. ? CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: retrospective case series; evidence: Class IV. PMID- 27367241 TI - Interrater and intrarater reliability of the Knosp scale for pituitary adenoma grading. AB - OBJECTIVE The goal of this study was to determine the interrater and intrarater reliability of the Knosp grading scale for predicting pituitary adenoma cavernous sinus (CS) involvement. METHODS Six independent raters (3 neurosurgery residents, 2 pituitary surgeons, and 1 neuroradiologist) participated in the study. Each rater scored 50 unique pituitary MRI scans (with contrast) of biopsy-proven pituitary adenoma. Reliabilities for the full scale were determined 3 ways: 1) using all 50 scans, 2) using scans with midrange scores versus end scores, and 3) using a dichotomized scale that reflects common clinical practice. The performance of resident raters was compared with that of faculty raters to assess the influence of training level on reliability. RESULTS Overall, the interrater reliability of the Knosp scale was "strong" (0.73, 95% CI 0.56-0.84). However, the percent agreement for all 6 reviewers was only 10% (26% for faculty members, 30% for residents). The reliability of the middle scores (i.e., average rated Knosp Grades 1 and 2) was "very weak" (0.18, 95% CI -0.27 to 0.56) and the percent agreement for all reviewers was only 5%. When the scale was dichotomized into tumors unlikely to have intraoperative CS involvement (Grades 0, 1, and 2) and those likely to have CS involvement (Grades 3 and 4), the reliability was "strong" (0.60, 95% CI 0.39-0.75) and the percent agreement for all raters improved to 60%. There was no significant difference in reliability between residents and faculty (residents 0.72, 95% CI 0.55-0.83 vs faculty 0.73, 95% CI 0.56-0.84). Intrarater reliability was moderate to strong and increased with the level of experience. CONCLUSIONS Although these findings suggest that the Knosp grading scale has acceptable interrater reliability overall, it raises important questions about the "very weak" reliability of the scale's middle grades. By dichotomizing the scale into clinically useful groups, the authors were able to address the poor reliability and percent agreement of the intermediate grades and to isolate the most important grades for use in surgical decision making (Grades 3 and 4). Authors of future pituitary surgery studies should consider reporting Knosp grades as dichotomized results rather than as the full scale to optimize the reliability of the scale. PMID- 27367242 TI - Effect of functional MRI-guided navigation on surgical outcomes: a prospective controlled trial in patients with arteriovenous malformations. AB - OBJECTIVE The impact of functional MRI (fMRI)-guided navigation on the surgical outcome of patients with arteriovenous malformations (AVMs) is undetermined. This large, randomized controlled trial (RCT) was designed to determine the safety and efficacy of fMRI-guided microsurgery of AVMs. This paper reports the preliminary results of the interim analysis. METHODS Between September 2012 and June 2015, eligible patients were randomized to the standard microsurgery group (control group) or the fMRI-guided surgery group (experimental group) in a 1:1 ratio. Patients in the control group underwent conventional digital subtraction angiography and MRI before surgery. The surgery was performed according to the standard procedure. However, patients in the experimental group underwent blood oxygen level-dependent (BOLD) fMRI and diffusion tensor imaging within 1 week before surgery. Moreover, preoperative eloquent brain tissue mapping and intraoperative fMRI navigation were performed in addition to the standard procedure. The preliminary end points were the total removal rate of AVMs and postoperative surgical complications. The primary end points were modified Rankin Scale (mRS) score (favorable: mRS Score 0-2; poor: mRS Score 3-6) and surgery related permanent functional deficits (S-PFD) at the last clinic visit (>= 6 months). Statistical analysis was performed using the statistical package from SPSS. RESULTS The interim analysis included 184 participants (93 in the experimental group and 91 in the control group). Patients were equally distributed between the 2 groups. Neither the preliminary nor the primary end points, including postoperative complications (p = 0.781), residual AVM (p = 1.000), last mRS score (p = 0.654), and S-PFD (p = 0.944) showed any significant difference between the control and experimental group. According to the results of the univariate analysis, eloquent adjacent brain tissue (OR 0.14; 95% CI 0.06 0.32; p < 0.001), large size of the nidus (OR 1.05; 95% CI 1.02-1.08; p = 0.002), or diffuse nidus (OR 3.05; 95% CI 1.42-6.58; p = 0.004) were all significantly associated with S-PFD. Additionally, a high Spetzler-Martin score (OR 3.54; 95% CI 2.08-6.02; p < 0.001), no previous hemorrhage (OR 2.35; 95% CI 1.00-5.54; p = 0.05), or a low preoperative mRS score (OR 0.42; 95% CI 0.17-1.00; p = 0.049) were also significantly associated with S-PFD. Multivariate analysis revealed that independent factors correlated with S-PFD were eloquent adjacent brain tissue (OR 0.17; 95% CI 0.04-0.70; p = 0.014) and low preoperative mRS score (OR 0.22; 95% CI 0.07-0.69; p = 0.009). CONCLUSIONS This preplanned interim analysis revealed no significant differences in the primary end points between the experimental and control group, prompting an early termination of this RCT. The preliminary data indicated that the additional intervention of fMRI navigation is not associated with a more favorable surgical outcome in patients with AVMs. The results indicated that eloquent adjacent brain tissue and a low preoperative mRS score are independent risk factors for S-PFD. Clinical trial registration no.: NCT01758211 ( clinicaltrials.gov ). PMID- 27367243 TI - Therapeutic effect of erythropoietin in patients with traumatic brain injury: a meta-analysis of randomized controlled trials. AB - OBJECTIVE Erythropoietin (EPO) exerts a neuroprotective effect in animal models of traumatic brain injury (TBI). However, its effectiveness in human patients with TBI is unclear. In this study, the authors conducted the first meta-analysis to assess the effectiveness and safety of EPO in patients with TBI. METHODS In December 2015, a systematic search was performed of PubMed, Web of Science, MEDLINE, Embase, the Cochrane Library databases, and Google Scholar. Only English language publications of randomized controlled trials (RCTs) using EPO in patients with TBI were selected for analysis. The assessed outcomes included mortality, favorable neurological outcome, hospital stay, and associated adverse effects. Continuous variables were presented as mean difference (MD) with a 95% confidence interval (CI). Dichotomous variables were presented as risk ratio (RR) or risk difference (RD) with a 95% CI. Statistical heterogeneity was examined using both I2 and chi-square tests. RESULTS Of the 346 studies identified in the search, 5 RCTs involving 915 patients met the inclusion criteria. The overall results demonstrated that EPO significantly reduced mortality (RR 0.69, 95% CI 0.49-0.96, p = 0.03) and shortened the hospitalization time (MD -7.59, 95% CI 9.71 to -5.46, p < 0.0001) for patients with TBI. Pooled results of favorable outcome (RR 1.00, 95% CI 0.88-1.15, p = 0.97) and deep vein thrombosis (DVT; RD 0.00, 95% CI -0.05 to 0.05, p = 1.00) did not show a significant difference. CONCLUSIONS The authors suggested that EPO is beneficial for patients with TBI in terms of reducing mortality and shortening hospitalization time without increasing the risk of DVT. However, its effect on improving favorable neurological outcomes did not reach statistical significance. Therefore, more well-designed RCTs are necessary to ascertain the optimum dosage and time window of EPO treatment for patients with TBI. PMID- 27367244 TI - Outcome after conservative management or surgical treatment for new-onset epilepsy in cerebral cavernous malformation. AB - OBJECTIVE The aim of this study was to determine seizure outcome, functional outcome, and the withdrawal of antiepileptic drugs (AEDs) after conservative or surgical treatment of patients with new-onset cavernoma-related epilepsy (CRE). METHODS The authors conducted a retrospective comparative observational study of 79 consecutive patients, each with a single sporadic cerebral cavernous malformation (CCM) and new-onset CRE. RESULTS Forty-one patients underwent initial surgery (IS), and 38 patients underwent initial conservative (IC) treatment. Of those in the latter group, 19 underwent delayed surgical (DS) treatment. At the last follow-up, 88%, 32%, and 79% of patients in the respective groups had been seizure free for at least 2 years (International League Against Epilepsy [ILAE] Class 1; IS vs IC, p < 0.0001) and 78%, 8%, and 58%, respectively, had been off AEDs (IS vs IC, p < 0.0001). The cumulative probability of staying seizure free (ILAE Class 1) during a 5-year period was 73% (mean seizure-free follow-up 49.8 +/- 2.7 months, 95% CI 44.4-55.1 months) for the IS group, 22% (mean 31.8 +/- 3.6 months, 95% CI 24.8-38.8 months) for the IC group, and 68% (mean 48.6 +/- 4.3 months, 95% CI 40.1-57.1 months) for the DS group (IS vs IC p < 0.001). Long-term operative morbidity was 3%, and long-term morbidity in the conservatively treated group was also 3%. CONCLUSIONS Patients with CCM and new-onset CRE who underwent IS treatment showed better results in seizure control and the discontinuation of AEDs than the conservatively treated patients. Operative morbidity was comparable to the morbidity from symptomatic CCM hemorrhage in the conservative group. Half of the patients who started with conservative treatment underwent subsequent surgical treatment; however, a longer duration of epilepsy prior to surgery did not worsen postoperative seizure outcome. PMID- 27367246 TI - Editorial. Classes of evidence in neurosurgery. PMID- 27367245 TI - ActiGait implantable drop foot stimulator in multiple sclerosis: a new indication. AB - OBJECTIVE Direct stimulation of the peroneal nerve by the ActiGait implantable drop foot stimulator is a potent therapy that was described previously for stroke related drop foot. The authors report here successful long-term application of the ActiGait implantable drop foot stimulator in patients with multiple sclerosis (MS). METHODS Six patients with MS and 2 years of persisting central leg paresis received an implantable ActiGait drop foot stimulator after successful surface test stimulation. Ten weeks and 1 year after surgery, their gait speed, endurance, and safety were evaluated. Patient satisfaction was assessed with a questionnaire. RESULTS In the 20-m gait test, stimulation with the ActiGait stimulator significantly reduced the time needed, on average, by approximately 23.6% 10 weeks after surgery, and the time improved further by 36.3% after 1 year. The median distance covered by patients with the stimulator after 6 minutes of walking increased significantly from 217 m to 321 m and remained stable for 1 year; the distance covered by patients after surface stimulation was 264 m. Patients with an implanted ActiGait stimulator noticed pronounced improvement in their mobility, social participation, and quality of life. CONCLUSIONS The ActiGait implantable drop foot stimulator improved gait speed, endurance, and quality of life in all patients over a period of 1 year. It may serve as a new therapeutic option for patients with MS-related drop foot. PMID- 27367247 TI - Increased expression of the histone H3 lysine 4 methyltransferase MLL4 and the histone H3 lysine 27 demethylase UTX prolonging the overall survival of patients with glioblastoma and a methylated MGMT promoter. AB - OBJECTIVE The purpose of the present study was to investigate the epigenetic and prognostic roles of an H3K4 methyltransferase (mixed lineage leukemia 4 [MLL4]) and H3K27 demethylase (ubiquitously transcribed tetratricopeptide repeat gene on X chromosome [UTX]) in progression-free survival (PFS) and overall survival (OS) of patients with glioblastoma (GBM) who were treated with radiotherapy, chemotherapy, or both after resection. In addition, the authors examined methylation at the promoter of the O-6-methylguanine-DNA methyltransferase ( MGMT) gene and other prognostic factors predicting length of PFS and OS in these patients. METHODS The medical records of 76 patients having a new diagnosis of histologically ascertained GBM in the period of January 2002 to December 2013 at the authors' institution were retrospectively reviewed. Immunohistochemical staining for MLL4 and UTX was performed on archived paraffin-embedded tissues obtained by biopsy or resection. The methylation status of the MGMT promoter in these tissues was determined by methylation-specific PCR analysis. RESULTS During the follow-up period (mean length 18.1 months, range 4.1-43.5 months), 68 (89.5%) of the patients died. The MGMT promoter was methylated in 49 patients (64.5%) and unmethylated in 27 (35.5%). The immunoreactivity pattern of UTX was identical to that of MLL4; increased expression of these 2 proteins was observed in samples from 34 patients (44.7%) and decreased expression in 42 patients (55.3%). The mean length of PFS was 9.2 months (95% CI 6.8-11.6 months). Extent of surgery, recursive partitioning analysis (RPA) class, and methylation status of the MGMT promoter were all associated with increased PFS in the multivariate analysis of factors predicting PFS. The mean length of OS was 18.6 months (95% CI 14.3-22.9 months). Patient age (p = 0.004), WHO performance status score (p = 0.019), extent of surgery (p = 0.007), RPA class (p = 0.036), methylation status of the MGMT promoter (p = 0.010), and increased expression of UTX-MLL4 (p = 0.001) were significantly associated with increased OS in multivariate analysis. Interestingly, in patients with an unmethylated MGMT promoter, immunoreactivity of UTX-MLL4 was not associated with changes in OS (p = 0.350). However, in the patients with a methylated MGMT promoter, increased UTX-MLL4 expression was strongly associated with increased OS (p < 0.001). CONCLUSIONS The results of this study suggest that increased expression of UTX-MLL4 positively influences the outcome of patients with GBM having a methylated MGMT promoter. Therefore, UTX-MLL4 immunoreactivity could be a useful predictor of the response to conventional treatment with radiotherapy or chemotherapy among GBM patients whose tumors have a methylated MGMT promoter. PMID- 27367248 TI - A prospective analysis of hypovitaminosis D and mortality in 400 patients in the neurocritical care setting. AB - OBJECTIVE Hypovitaminosis D is highly prevalent among the general population. Studies have shown an association between hypovitaminosis D and multiple negative outcomes in critical care patients, but there has been no prospective evaluation of vitamin D in the neurological critical care population. The authors examined the impact of vitamin D deficiency on in-hospital mortality and a variety of secondary outcomes. METHODS The authors prospectively collected 25-hydroxy vitamin D levels of all patients admitted to the neurocritical care unit (NCCU) of a quaternary-care center over a 3-month period. Demographic data, illness acuity, in-hospital mortality, infection, and length of hospitalization were collected. Univariate and multivariable logistic regression were used to examine the effects of vitamin D deficiency. RESULTS Four hundred fifteen patients met the inclusion criteria. In-hospital mortality was slightly worse (9.3% vs 4.5%; p = 0.059) among patients with deficient vitamin D (<= 20 ng/dl). There was also a higher rate of urinary tract infection in patients with vitamin D deficiency (12.4% vs 4.2%; p = 0.002). For patients admitted to the NCCU on an emergency basis (n = 285), higher Simplified Acute Physiology Score II (OR 13.8, 95% CI 1.7 110.8; p = 0.014), and vitamin D deficiency (OR 3.0, 95% CI 1.0-8.6; p = 0.042) were significantly associated with increased in-hospital mortality after adjusting for other factors. CONCLUSIONS In the subset of patients admitted to the NCCU on an emergency basis, vitamin D deficiency is significantly associated with higher in-hospital mortality. Larger studies are needed to confirm these findings and to investigate the role of vitamin D supplementation in these patients. PMID- 27367250 TI - Special Section Guest Editorial:Selected Topics in Biophotonics: Photoacoustic Tomography and Fiber-Based Lasers and Supercontinuum Sources. PMID- 27367249 TI - Infrared inhibition of embryonic hearts. AB - Infrared control is a new technique that uses pulsed infrared lasers to thermally alter electrical activity. Originally developed for nerves, we have applied this technology to embryonic hearts using a quail model, previously demonstrating infrared stimulation and, here, infrared inhibition. Infrared inhibition enables repeatable and reversible block, stopping cardiac contractions for several seconds. Normal beating resumes after the laser is turned off. The block can be spatially specific, affecting propagation on the ventricle or initiation on the atrium. Optical mapping showed that the block affects action potentials and not just calcium or contraction. Increased resting intracellular calcium was observed after a 30-s exposure to the inhibition laser, which likely resulted in reduced mechanical function. Further optimization of the laser illumination should reduce potential damage. Stopping cardiac contractions by disrupting electrical activity with infrared inhibition has the potential to be a powerful tool for studying the developing heart. PMID- 27367251 TI - Ceramic bracket debonding with Tm:fiber laser. AB - Lasers have the potential for reducing the required debonding force and can prevent the mechanical damage given to the enamel surface as a result of conventional debonding procedure. However, excessive thermal effects limit the use of lasers for debonding purposes. The aim of this study was to investigate the optimal parameters of 1940-nm Tm:fiber laser for debonding ceramic brackets. Pulling force and intrapulpal temperature measurements were done during laser irradiation simultaneously. A laser beam was delivered in two different modes: scanning the fiber tip on the bracket surface with a Z shape movement or direct application of the fiber tip at one point in the center of the bracket. Results showed that debonding force could be decreased significantly compared to the control samples, in which brackets were debonded by only mechanical force. Intrapulpal temperature was kept equal or under the 5.5 degrees C threshold value of probable thermal damage to pulp. Scanning was found to have no extra contribution to the process. It was concluded that using 1940-nm Tm:fiber laser would facilitate the debonding of ceramic brackets and can be proposed as a promising debonding tool with all the advantageous aspects of fiber lasers. PMID- 27367252 TI - Fabrication of various optical tissue phantoms by the spin-coating method. AB - Although numerous studies have been performed to fabricate various optical tissue phantom (OTP) models, the fabrication of OTPs that simulate skin layers is laborious and time-consuming owing to the intricate characteristics of skin tissue. This study presents various OTP models that optically and structurally simulate the epidermis-dermis skin layer. The spin-coating method was employed to reproduce a uniform thin layer that mimics the epidermis layer, and the fabrication parameters were optimized for epoxy and silicone reference materials. Various OTP models simulating blood vessels and hyperpigmentation lesions were fabricated using the two reference materials to determine their feasibility. The suitability of each of the two reference materials for OTP fabrication was qualitatively evaluated by comparing the quality of the OTP models. PMID- 27367253 TI - Super-resolution imaging of ciliary microdomains in isolated olfactory sensory neurons using a custom two-color stimulated emission depletion microscope. AB - We performed stimulated emission depletion (STED) imaging of isolated olfactory sensory neurons (OSNs) using a custom-built microscope. The STED microscope uses a single pulsed laser to excite two separate fluorophores, Atto 590 and Atto 647N. A gated timing circuit combined with temporal interleaving of the different color excitation/STED laser pulses filters the two channel detection and greatly minimizes crosstalk. We quantified the instrument resolution to be ~81 and ~44 nm, for the Atto 590 and Atto 647N channels. The spatial separation between the two channels was measured to be under 10 nm, well below the resolution limit. The custom-STED microscope is incorporated onto a commercial research microscope allowing brightfield, differential interference contrast, and epifluorescence imaging on the same field of view. We performed immunolabeling of OSNs in mice to image localization of ciliary membrane proteins involved in olfactory transduction. We imaged Ca2+-permeable cyclic nucleotide gated (CNG) channel (Atto 594) and adenylyl cyclase type III (ACIII) (Atto 647N) in distinct cilia. STED imaging resolved well-separated subdiffraction limited clusters for each protein. We quantified the size of each cluster to have a mean value of 88+/-48 nm and 124+/-43 nm, for CNG and ACIII, respectively. STED imaging showed separated clusters that were not resolvable in confocal images. PMID- 27367254 TI - Microwave-heating-coupled photoacoustic radar for tissue diagnostic imaging. AB - An investigation of microwave (MW) heating effects on biotissue for enhancing photoacoustic radar (PAR) signals was conducted. Localized tissue heating generated by MWs was used to improve PAR imaging depth and signal-to-noise ratio (SNR). Elevated temperatures were measured with thermocouples in ex vivo bovine muscle. The measured temperature rise on the heated spot surface by MWs was in agreement with theoretical predictions. The study showed localized MW heating can increase the photoacoustic imaging depth by 11%, and the SNR by 5% in ex vivo bovine muscle. PMID- 27367255 TI - Photoacoustic imaging with an acoustic lens detects prostate cancer cells labeled with PSMA-targeting near-infrared dye-conjugates. AB - There is an urgent need for sensitive and specific tools to accurately image early stage, organ-confined human prostate cancers to facilitate active surveillance and reduce unnecessary treatment. Recently, we developed an acoustic lens that enhances the sensitivity of photoacoustic imaging. Here, we report the use of this device in conjunction with two molecular imaging agents that specifically target the prostate-specific membrane antigen (PSMA) expressed on the tumor cell surface of most prostate cancers. We demonstrate successful imaging of phantoms containing cancer cells labeled with either of two different PSMA-targeting agents, the ribonucleic acid aptamer A10-3.2 and a urea-based peptidomimetic inhibitor, each linked to the near-infrared dye IRDye800CW. By specifically targeting cells with these agents linked to a dye chosen for optimal signal, we are able to discriminate prostate cancer cells that express PSMA. PMID- 27367256 TI - Mechanical Nasal Dilators for the Management of Nasal Obstruction. PMID- 27367257 TI - Progranulin protects against endotoxin-induced acute kidney injury by downregulating renal cell death and inflammatory responses in mice. AB - Progranulin (PGRN), a pluripotent secreted growth factor, is involved in various physiologic and disease processes. However, the role of PGRN in endotoxin-induced septic acute kidney injury (AKI) remains unknown. The objective of this study is to investigate the protective effects of PGRN on an endotoxin-induced AKI mouse model by using PGRN-deficient mice and recombinant PGRN (rPGRN) pretreatment. PGRN levels were increased in kidneys of wild-type (WT) mice at 6 and 24h after lipopolysaccharide (LPS) injection. Renal function detection, hematoxylin and eosin staining, immunohistochemical staining, ELISA and in situ terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick-end labeling were used to reveal tissue injury, inflammatory cell infiltration, production of inflammatory mediators and cell death in mouse kidneys after LPS injection. PGRN deficiency resulted in severe kidney injury and increased apoptotic death, inflammatory cell infiltration, production of pro-inflammatory mediators and the expression and nucleus-to-cytoplasmic translocation of HMGB1 in the kidney. In addition, rPGRN administration before LPS treatment ameliorated the endotoxin induced AKI in WT mice. PGRN may be a novel biologic agent with therapeutic potential for endotoxin-induced septic AKI possibly by inhibiting LPS-induced renal cell death and inflammatory responses in mice. PMID- 27367258 TI - The influence of non-ionisable excipients on precipitation parameters measured using the CheqSol method. AB - OBJECTIVES: The aim of this study was to determine the influence of non-ionisable excipients hydroxypropyl-beta-cyclodextrin (HPbetaCD) and poloxamers 407 and 188 on the supersaturation and precipitation kinetics of ibuprofen, gliclazide, propranolol and atenolol induced through solution pH shifts using the CheqSol method. METHODS: The drug's kinetic and intrinsic aqueous solubilities were measured in the presence of increasing excipient concentrations using the CheqSol method. Experimental data rate of change of pH with time was also examined to determine excipient-induced parachute effects and influence on precipitation rates. KEY FINDINGS: The measured kinetic and intrinsic solubilities provide a determination of the influence of each excipient on supersaturation index, and the area under the CheqSol curve can measure the parachute capability of excipients. The excipients influence on precipitation kinetics can be measured with novel parameters; for example, the precipitation pH or percentage ionised drug at the precipitation point, which provide further information on the excipient-induced changes in precipitation performance. CONCLUSION: This method can therefore be employed to measure the influence of non-ionisable excipients on the kinetic solubility behaviour of supersaturated solutions of ionisable drugs and to provide data, which discriminates between excipient systems during precipitation. PMID- 27367259 TI - Integrating MRI for the diagnosis of prostate cancer. AB - PURPOSE OF REVIEW: We review recent developments in prostate MRI for prostate cancer diagnosis. RECENT FINDINGS: Large series have strengthened the case for the use of MRI prior to subsequent biopsy to maximize the detection of clinically significant disease, and reduce the detection of clinically insignificant disease. This has effectively moved the discussion on from whether MRI is useful in prostate cancer detection to how best to use it, and at which time point. The Prostate Imaging- Reporting And Data System (PIRADS) group have published a second version of the PIRADS criteria for prostate MRI, covering acquisition, interpretation, and reporting both for clinical practice and data collection for research.There is debate about the commonly used and more prescriptive PIRADS system versus the less prescriptive systems based on overall clinical impression of clinically significant disease (e.g. Likert or simplified quantum scoring). Studies suggest that the Likert or simplified quantum scoring approach may outperform PIRADSv2. Published data are conflicting on whether software-assisted fusion of MRI lesions to ultrasound used at biopsy is more effective than visual registration by a trained operator. SUMMARY: The use of prostate MRI is increasing worldwide, and the debate now focuses on how best to use it to optimize the detection of clinically significant disease. PMID- 27367260 TI - The Vitamin E Radical Probed by Anion Photoelectron Imaging. AB - The biological antioxidant activity of vitamin E has been related to the stability of the tocopheroxyl radical. Using anion photoelectron imaging and electronic structure calculations, the four tocopheroxyl components of vitamin E have been studied in the gas phase and have yielded the adiabatic electron affinity of the alpha-, beta/gamma-, and delta-tocopheroxyl radicals. Using these values, the bond dissociation enthalpy of the O-H bond of tocopherol has been estimated and is consistent with previous studies and with the trends in biological activity. Differences in the photoelectron angular distributions have been interpreted to result from changes in the symmetry of the molecular orbitals from which the electron was detached. PMID- 27367261 TI - Falls and Wrist Fracture: Relationship to Women's Functional Status after Age 50. AB - Women experience a rapid rise in the incidence of wrist fracture after age 50. Accordingly, this study aimed to (1) determine the internal and environmental fall-related circumstances resulting in a wrist fracture, and (2) examine the relationship of functional status to these circumstances. Women aged 50 to 94 years reported on the nature of the injury (n = 99) and underwent testing for physical activity status, balance, strength, and mobility (n = 72). The majority of falls causing wrist fracture occurred outdoors, during winter months, as a result of a slip or trip while walking. Half of these falls resulted in other injuries including head, neck, and spine injuries. Faster walking speed, lower grip strength, and higher balance confidence were significantly associated with outdoor versus indoor falls and slips and trips versus other causes. This study provides insights into potential screening and preventive measures for fall related wrist fractures in women. PMID- 27367262 TI - A Crystalline Mesolamellar Gallium Phosphate with Zwitterionic-type Templates Exhibiting Green Afterglow Property. AB - We synthesized a unique layer structure of gallium phosphates containing zwitterionic-type templates under mild hydrothermal reactions. The zwitterionic type templates, formed of long-alkyl-chain diamine cations and biphenyldicarboxylate anions, resided upright between adjacent layers, propping the interlayer distance up to 2.2 nm. For the first time, the mesoscale interlayer templates were sufficiently well-ordered to afford elucidation to the atomic-level. The mesolamellar (HDADD)2(BPDC)0.5[Ga3(OH)2(HPO4)4] (1; DADD = 1,12 diaminododecane, BPDC = 4,4'-biphenyldicarboxylate) was composed of inorganic layers built up exclusively with a unique type of heptameric unit which featured an unprecedented trimeric cluster of [Ga3(OH)2O12]. Unexpectedly, compound 1 possessed an unusual green afterglow. To interpret the interesting photoluminescence (PL) property, three other low-dimensional structures related to 1 were prepared as well. The data from PL and electron paramagnetic resonance indicated that the afterglow was mainly attributed to lattice defects and the orientations of BPDC. PMID- 27367263 TI - Finding success in failure: using latent profile analysis to examine heterogeneity in psychosocial functioning among heavy drinkers following treatment. AB - AIMS: To estimate differences in post-treatment psychosocial functioning among treatment 'failures' (i.e. heavy drinkers, defined as 4+/5+ drinks for women/men) from two large multi-site clinical trials and to compare these levels of functioning to those of the purported treatment 'successes' (i.e. non-heavy drinkers). DESIGN: Separate latent profile analyses of data from two of the largest alcohol clinical trials conducted in the United States, COMBINE (Combined Pharmacotherapies and Behavioral Interventions) and Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity), comparing psychosocial outcomes across derived classes of heterogeneous treatment responders. SETTING: Eleven US academic sites in COMBINE, 27 US treatment sites local to nine research sites in Project MATCH. PARTICIPANTS: A total of 962 individuals in COMBINE (69% male, 77% white, mean age: 44 years) treated January 2001 to January 2004 and 1528 individuals in Project MATCH (75% male, 80% white, mean age: 40 years) treated April 1991 to September 1994. MEASUREMENTS: In COMBINE, we analyzed health, quality of life, mental health symptoms and alcohol consequences 12 months post baseline. In Project MATCH, we examined social functioning, mental health symptoms and alcohol consequences 15 months post-baseline. FINDINGS: Latent profile analysis of measures of functioning in both samples supported a three profile solution for the group of treatment 'failures', characterized by high-, average- and low-functioning individuals. The high-functioning treatment 'failures' generally performed better across measures of psychosocial functioning at follow-up than participants designated treatment 'successes' by virtue of being abstainers or light drinkers. CONCLUSIONS: Current United States Food and Drug Administration guidance to use heavy drinking as indicative of treatment 'failure' fails to take into account substantial psychosocial improvements made by individuals who continue occasionally to drink heavily post-treatment. PMID- 27367264 TI - Depressed myocardial energetic efficiency is associated with increased cardiovascular risk in hypertensive left ventricular hypertrophy. AB - BACKGROUND AND PURPOSE: Myocardial mechano-energetic efficiency (MEE) can be easily approximated by the ratio of stroke work [i.e. SBP times stroke volume (SV)] to a rough estimate of energy consumption, the 'double product' [SBP times heart rate (HR)], which can be simplified as SV/HR. We evaluated whether MEE is associated with adverse prognosis in relation to the presence of left ventricular hypertrophy (LVH). METHODS: Hypertensive participants of the Campania Salute Network (n = 12 353) without prevalent coronary or cerebrovascular disease and with ejection fraction more than 50% were cross-sectionally and longitudinally analyzed, over a median follow-up of 31 months. MEE was estimated by echocardiographic SV (z-derived)/(HR * 0.6). RESULTS: Due to the close relation with left ventricular mass (LVM) (P < 0.0001), MEE was normalized for LVM (MEEi) and divided into quartiles. The lowest quartile of MEEi (<0.29 ml/s per g) was considered 'low MEEi'. MEEi was greater in women than in men (P < 0.0001). Progressively lower MEEi was associated with older age, male sex, obesity, diabetes, LVH, concentric geometry, inappropriate LVM and diastolic dysfunction, more use of antihypertensive therapy, and higher BP (all P < 0.002). In Cox regression, after controlling for LVH, age, sex, and average follow-up SBP, low MEEi exhibited increased hazard of composite fatal and nonfatal cardiovascular end-points (P < 0.01), independently of antihypertensive therapy and associated cardiovascular risk factors. CONCLUSION: A simple estimate of low myocardial mechano-energetic efficiency is associated with altered metabolic profile, LVH, concentric left ventricular geometry, and diastolic dysfunction and predicts cardiovascular end-points, independently of age, sex, LVH antihypertensive therapy, and cardiovascular risk factors. PMID- 27367265 TI - Optimizing sleep to maximize performance: implications and recommendations for elite athletes. AB - Despite a growing body of literature demonstrating a positive relationship between sleep and optimal performance, athletes often have low sleep quality and quantity. Insufficient sleep among athletes may be due to scheduling constraints and the low priority of sleep relative to other training demands, as well as a lack of awareness of the role of sleep in optimizing athletic performance. Domains of athletic performance (e.g., speed and endurance), neurocognitive function (e.g., attention and memory), and physical health (e.g., illness and injury risk, and weight maintenance) have all been shown to be negatively affected by insufficient sleep or experimentally modeled sleep restriction. However, healthy adults are notoriously poor at self-assessing the magnitude of the impact of sleep loss, underscoring the need for increased awareness of the importance of sleep among both elite athletes and practitioners managing their care. Strategies to optimize sleep quality and quantity in athletes include approaches for expanding total sleep duration, improving sleep environment, and identifying potential sleep disorders. PMID- 27367266 TI - The Ideological and Political Dimensions of the Anti-Smoking and Anti-Drinking Video Advertisements in the Republic of Moldova. AB - Based on the critical approach in health communication, along with Habermas's theory of legitimation and Ellul's theory of propaganda, this qualitative study analyzes the political and ideological dimensions of the video advertisements used in the 2012 anti-smoking and 2014 anti-drinking campaigns in the Republic of Moldova. This analysis shows that these health videos support male domination and exclusion of the poor and legitimate the current political leadership with its declared pro-European orientation. This study uniquely contributes to the critical approach in health communication by focusing on the post-Soviet context in which statehood and national identity are unstable and societies are torn between the Russian and (post-)Soviet influences on one hand and European aspirations on the other. Drawing on critical scholarship in global health communication, this article calls for greater respect and recognition of Moldova's local culture and definition of health. PMID- 27367267 TI - Canakinumab for the treatment of active systemic juvenile idiopathic arthritis. AB - INTRODUCTION: Canakinumab, a fully human monoclonal antibody against interleukin 1beta, is a relatively new medication approved for treatment of systemic juvenile idiopathic arthritis (SJIA). Here, we review data supporting use of canakinumab for patients with active SJIA, as compared to other available biologic medications. AREAS COVERED: This article provides an overview of chemistry of canakinumab as well as the phase II and phase III trials that led to approval for treatment of active SJIA. To undertake this review, the authors performed literature search using Pubmed, with keywords 'canakinumab,' 'biologic,' 'anti-IL 1B,' and 'systemic juvenile idiopathic arthritis,' focusing on publications within the last 5 years. Expert commentary: Canakinumab has shown efficacy in treatment of SJIA with active systemic features including fever. There is no evidence to suggest increased risk of macrophage activation syndrome. Its use in the treatment of chronic arthritis without active systemic features has not been approved and warrants further study. PMID- 27367268 TI - Computational Assessment of the Relation Between Embolism Source and Embolus Distribution to the Circle of Willis for Improved Understanding of Stroke Etiology. AB - Stroke caused by an embolism accounts for about a third of all stroke cases. Understanding the source and cause of the embolism is critical for diagnosis and long-term treatment of such stroke cases. The complex nature of the transport of an embolus within large arteries is a primary hindrance to a clear understanding of embolic stroke etiology. Recent advances in medical image-based computational hemodynamics modeling have rendered increasing utility to such techniques as a probe into the complex flow and transport phenomena in large arteries. In this work, we present a novel, patient-specific, computational framework for understanding embolic stroke etiology, by combining image-based hemodynamics with discrete particle dynamics and a sampling-based analysis. The framework allows us to explore the important question of how embolism source manifests itself in embolus distribution across the various major cerebral arteries. Our investigations illustrate prominent numerical evidence regarding (i) the size/inertia-dependent trends in embolus distribution to the brain; (ii) the relative distribution of cardiogenic versus aortogenic emboli among the anterior, middle, and posterior cerebral arteries; (iii) the left versus right brain preference in cardio-emboli and aortic-emboli transport; and (iv) the source destination relationship for embolisms affecting the brain. PMID- 27367269 TI - Multiple Citation Indicators and Their Composite across Scientific Disciplines. AB - Many fields face an increasing prevalence of multi-authorship, and this poses challenges in assessing citation metrics. Here, we explore multiple citation indicators that address total impact (number of citations, Hirsch H index [H]), co-authorship adjustment (Schreiber Hm index [Hm]), and author order (total citations to papers as single; single or first; or single, first, or last author). We demonstrate the correlation patterns between these indicators across 84,116 scientists (those among the top 30,000 for impact in a single year [2013] in at least one of these indicators) and separately across 12 scientific fields. Correlation patterns vary across these 12 fields. In physics, total citations are highly negatively correlated with indicators of co-authorship adjustment and of author order, while in other sciences the negative correlation is seen only for total citation impact and citations to papers as single author. We propose a composite score that sums standardized values of these six log-transformed indicators. Of the 1,000 top-ranked scientists with the composite score, only 322 are in the top 1,000 based on total citations. Many Nobel laureates and other extremely influential scientists rank among the top-1,000 with the composite indicator, but would rank much lower based on total citations. Conversely, many of the top 1,000 authors on total citations have had no single/first/last authored cited paper. More Nobel laureates of 2011-2015 are among the top authors when authors are ranked by the composite score than by total citations, H index, or Hm index; 40/47 of these laureates are among the top 30,000 by at least one of the six indicators. We also explore the sensitivity of indicators to self citation and alphabetic ordering of authors in papers across different scientific fields. Multiple indicators and their composite may give a more comprehensive picture of impact, although no citation indicator, single or composite, can be expected to select all the best scientists. PMID- 27367270 TI - Treatment of Acute Purulent Dacryocystitis by Early Bicanalicular Silicone Intubation: Safety, Efficacy, and Outcomes. AB - PURPOSE: To evaluate the safety, efficacy, and outcomes of early bicanalicular silicone intubation in the treatment of acute purulent dacryocystitis. METHODS: This prospective interventional case series focused on acute purulent dacryocystitis from February 2010 to March 2014. Of the 21 cases, 16 cases were treated at the Fujian Provincial Hospital, and five cases were treated at the Lianjiang Hospital. Bicanalicular silicone intubation was inserted in the original lacrimal duct within 10 days after abscess decompression by pus aspiration method and systemic antibiotic application. Data collection included demographic profiles, perioperative and postoperative complications, and revision surgery. Resolution of signs and symptoms of acute purulent dacryocystitis, as well as successful anatomical patency assessed by irrigation, was evaluated. Follow-up times were more than 12 months, and ranged from 14 to 63 months. RESULTS: All patients showed remarkable improvement of pain and swelling within 48 hours. Resolution of the erythema and edema was observed within one week after bicanalicular silicone intubation combined with topical antibiotic lavage. No intraoperative and postoperative complications were observed. After initial bicanalicular silicone intubation, anatomical success was observed in 66.7% (14/21) of the patients. Of the remaining seven patients who presented with severe reflux in irrigation, two patients chose re-intubation and five patients underwent standard external dacryocystorhinostomy. All patients had anatomical success at last follow-up. CONCLUSION: Early bicanalicular silicone intubation appears to be a safe, effective, and simple procedure, which offers a reasonable option in the treatment of acute purulent dacryocystitis, especially for those developing and underdeveloped areas. PMID- 27367271 TI - Comparison of three different conjugation strategies in the construction of herceptin-bearing paclitaxel-loaded nanoparticles. AB - Research on quantitatively controlling the ligand density on the surface of nanocarriers is in the frontier and becomes a technical difficulty for targeted delivery system designing. In this study, we developed an improved pre conjugation (Imp) strategy, in which herceptin as a ligand was pre-conjugated with DSPE-PEG2000-Mal via chemical cross-linking, followed by conjugation onto the surface of pre-prepared paclitaxel-loaded PLGA/DODMA nanoparticles (PDNs) through hydrophobic interaction and electrostatic attraction for paclitaxel delivery. Compared with the post-conjugation (Pos) strategy, in which the ligand was conjugated onto the nanoparticle surface after the preparation of the nanoparticles, it realized a precise control targeting effect via adjustment of the herceptin density on the surface of the nanoparticles. Within the range of 0 20% of DSPE-PEG2000-herceptin in the blend, it showed a linear relation with the ligand density on the surface of the nanoparticles. The Imp strategy protected the bioactivity of the ligand during the preparation of nanoparticles. At the same time it avoided the waste of an excess amount of herceptin to drive the conjugation reaction in comparison with the post-conjugation (Pos) strategy. The nanoparticles from the Imp strategy showed much better cytotoxicity (p < 0.001), tumor targeting and cellular uptake efficiency (p < 0.001) than that of the other strategies in BT474 cells, in which BT474 cells were HER2 receptor over expression breast cancer cell lines. A significant reduction in cellular uptake of the nanoparticles from the Imp strategy was observed in the presence of sucrose and cytochalasin D, indicating that clathrin-mediated and caveolae dependent endocytosis was as a primary mechanism of cellular entry for these antibody-modified nanoparticles. PMID- 27367272 TI - MPT0B098, a Microtubule Inhibitor, Suppresses JAK2/STAT3 Signaling Pathway through Modulation of SOCS3 Stability in Oral Squamous Cell Carcinoma. AB - Microtubule inhibitors have been shown to inhibit Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signal transduction pathway in various cancer cells. However, little is known of the mechanism by which the microtubule inhibitors inhibit STAT3 activity. In the present study, we examined the effect of a novel small-molecule microtubule inhibitor, MPT0B098, on STAT3 signaling in oral squamous cell carcinoma (OSCC). Treatment of various OSCC cells with MPT0B098 induced growth inhibition, cell cycle arrest and apoptosis, as well as increased the protein level of SOCS3. The accumulation of SOCS3 protein enhanced its binding to JAK2 and TYK2 which facilitated the ubiquitination and degradation of JAK2 and TYK2, resulting in a loss of STAT3 activity. The inhibition of STAT3 activity led to sensitization of OSCC cells to MPT0B098 cytotoxicity, indicating that STAT3 is a key mediator of drug resistance in oral carcinogenesis. Moreover, the combination of MPT0B098 with the clinical drug cisplatin or 5-FU significantly augmented growth inhibition and apoptosis in OSCC cells. Taken together, our results provide a novel mechanism for the action of MPT0B098 in which the JAK2/STAT3 signaling pathway is suppressed through the modulation of SOCS3 protein level. The findings also provide a promising combinational therapy of MPT0B098 for OSCC. PMID- 27367273 TI - Functionalized Mesoporous Silica Nanoparticle with Antioxidants as a New Carrier That Generates Lower Oxidative Stress Impact on Cells. AB - Mesoporous silica nanoparticles (MSNs) were covalently coated with antioxidant molecules, namely, caffeic acid (MSN-CAF) or rutin (MSN-RUT), in order to diminish the impact of oxidative stress induced after transfection into cells, thus generating safer carriers used for either drug delivery or other applications. Two cellular models involved in the entry of NPs in the body were used for this purpose: the intestinal Caco-2 and the epidermal HaCaT cell lines. Rutin gave the best results in terms of antioxidant capacities preservation during coupling procedures, cellular toxicity alleviation, and decrease of ROS level after 24 h incubation of cells with grafted nanoparticles. These protective effects of rutin were found more pronounced in HaCaT than in Caco-2 cells, indicating some cellular specificity toward defense against oxidative stress. In order to gain more insight about the Nrf2 response, a stable transfected HaCaT cell line bearing repeats of the antioxidant response element (ARE) in front of a luciferase reporter gene was generated. In this cell line, both tBHQ and quercetin (Nrf2 agonists), but not rutin, were able to induce, in a dose dependent fashion, the luciferase response. Interestingly, at high concentration, MSN-RUT was able to induce a strong Nrf2 protective response in HaCaT cells, accompanied by a comparable induction of HO-1 mRNA. The level of these responses was again less important in Caco-2 cells. To conclude, in keratinocyte cell line, the coupling of rutin to silica nanoparticles was beneficial in term of ROS reduction, cellular viability, and protective effects mediated through the activation of the Nrf2 antioxidant pathway. PMID- 27367274 TI - Stable and Reusable Electrochemical Biosensor for Poly(ADP-ribose) Polymerase and Its Inhibitor Based on Enzyme-Initiated Auto-PARylation. AB - A stable and reusable electrochemical biosensor for the label-free detection of poly(ADP-ribose) polymerase (PARP) is designed in this work. C-kit-1, a thiol modified G-quadruplex oligonucleotide, is first self-assembled on a gold electrode surface. The G-quadruplex structure of c-kit-1 can specifically tether and activate PARP, resulting in the generation of negatively charged poly(ADP ribose) polymer (PAR). On the basis of electrostatic attraction, PAR facilitates the surface accumulation of positively charged electrochemical signal molecules. Through the characterization of electrochemical signal molecules, the label-free quantification of PARP is simply implemented. On the basis of the proposed method, selective quantification of PARP can be achieved over the linear range from 0.01 to 1 U with a calculated detection limit of 0.003U. Further studies also demonstrate the applicability of the proposed method to biosamples revealing the broad potential in practical applications. Furthermore, inhibitor of PARP has also been detected with this biosensor. Meanwhile, benefited from self-assembly on solid surface, this biosensor possesses two important features, i.e., reusability and stability, which are desirable in related biosensors. PMID- 27367275 TI - Methodological challenges when doing research that includes ethnic minorities: a scoping review. AB - BACKGROUND: There are challenging methodological issues in obtaining valid and reliable results on which to base occupational therapy interventions for ethnic minorities. The aim of this scoping review is to describe the methodological problems within occupational therapy research, when ethnic minorities are included. METHOD: A thorough literature search yielded 21 articles obtained from the scientific databases PubMed, Cinahl, Web of Science and PsychInfo. Analysis followed Arksey and O'Malley's framework for scoping reviews, applying content analysis. RESULTS: The results showed methodological issues concerning the entire research process from defining and recruiting samples, the conceptual understanding, lack of appropriate instruments, data collection using interpreters to analyzing data. CONCLUSION: In order to avoid excluding the ethnic minorities from adequate occupational therapy research and interventions, development of methods for the entire research process is needed. It is a costly and time-consuming process, but the results will be valid and reliable, and therefore more applicable in clinical practice. PMID- 27367277 TI - Ion Environments in Mn(2+)-Doped Polyelectrolyte Complexes: Dilute Magnetic Saloplastics. AB - Amorphous hydrated complexes of the polyelectrolytes poly(styrene sulfonate) (PSS) and poly(diallyldimethylammonium) were doped with the spin-5/2 ion Mn(2+). X-band electron paramagnetic resonance (EPR) measurements of the Mn(2+) spins within these stoichiometric polyelectrolyte complexes (PECs) revealed an octahedral coordination environment, similar to that observed in aqueous solutions of Mn(2+). This octahedral symmetry of the [Mn(H2O)6](2+) complexes, observed in fully hydrated PECs, is somewhat distorted because of the wide range of ion pairs possible with the sulfonate group on PSS. As the Mn(2+) concentration was increased, the linewidths broadened, indicating the dominance of dipolar broadening over exchange narrowing in determining the linewidths; that is, any exchange narrowing was masked by the large dipolar broadening. The calculated linewidths were used to estimate the strengths of the dipolar interactions, and hence the distances between the Mn(2+) spins, on the basis of a simple model of regularly spaced spins. The distances calculated by this method were roughly comparable to the geometric average distances calculated on the basis of the Mn(2+) concentrations and densities of the doped PEC samples. From a comparison of their EPR spectra, the ion environments in the doped, fully hydrated PECs were found to be similar to those in hydrated classical ion exchange resins. EPR spectra before and after drying of the PECs indicate the replacement of octahedrally coordinated water by oxide anions from the polyanion chain and the corresponding loss of the symmetric environment of Mn(2+) ions. PMID- 27367276 TI - Gambir, "Gambir Sarawak" and toad venom. PMID- 27367278 TI - Extended bandwidth real-ear measurement accuracy and repeatability to 10 kHz. AB - OBJECTIVE: Direct real-ear measurement to the 4-6 kHz range can be measured with suitable accuracy and repeatability. This study evaluates extended bandwidth measurement accuracy and repeatability using narrowband and wideband signal analysis. DESIGN: White noise was measured in female ear canals at four insertion depths using one-third and one-twenty-fourth octave band averaging. STUDY SAMPLE: Fourteen female adults with reported normal hearing and middle-ear function participated in the study. RESULTS: Test-retest differences were within +/-2 dB for typical frequency bandwidths at insertion depths administered in clinical practice, and for up to 8 kHz at the experimental 30 mm insertion depth. The 28 mm insertion depth was the best predictor of ear canal levels measured at the 30 mm insertion depth. There was no effect of signal analysis bandwidth on accuracy or repeatability. CONCLUSIONS: Clinically feasible 28 mm probe tube insertions reliably measured up to 8 kHz and predicted intensities up to 10 kHz measured at the 30 mm insertion depth more accurately than did shallower insertion depths. Signal analysis bandwidth may not be an important clinical issue at least for one third and one-twenty-fourth octave band analyses. PMID- 27367279 TI - The Effects of Turner Syndrome, 45,X on Obstetric and Neonatal Outcomes: A Retrospective Cohort Evaluation. AB - Objective This study aims to evaluate the perinatal and neonatal outcomes associated with prenatal diagnosis of 45,X, both with and without fetal cardiac anomalies. Study Design A retrospective cohort of singleton pregnancies in California, 2005 to 2008, using vital statistics and International Classification of Diseases, Ninth Revision data, identifying prenatally diagnosed 45,X. Outcomes included preterm delivery, preeclampsia, intrauterine fetal demise (IUFD), cesarean section, small for gestational age (SGA), neonatal death, and infant death. Bivariate and multivariate analyses were used to compare pregnancies and neonates with and without 45,X. Prenatally diagnosed cardiac anomalies were also considered. Results Of the 2,029,000 deliveries, 138 had prenatally diagnosed 45,X. Out of these 138 deliveries, 22 had a prenatally diagnosed cardiac anomaly. Compared with unaffected pregnancies, those with fetal 45,X had higher rates of preterm delivery (19.5 vs. 9.9%, p = 0.001), cesarean section (44.2 vs. 30.2%, p < 0.0001), and SGA (21.5 vs. 6.3%, p < 0.0001). The affected cohort had no IUFDs. Neonatal death was 14.5 times higher in the 45,X cohort (p < 0.0001). Of only infants with cardiac anomalies, neonatal death was significantly more likely in those with 45,X (p = 0.005). In adjusted analysis, risk of SGA (< 3rd percentile), neonatal death, and infant death remained increased for infants with 45,X while controlling for fetal cardiac anomalies. Conclusion Prenatally diagnosed 45,X was associated with increased risk of cesarean section, and adverse neonatal outcomes, including mortality. PMID- 27367280 TI - Birthweight Extremes and Neonatal and Childhood Outcomes after Preterm Premature Rupture of Membranes. AB - Objective To determine the association between birthweight extremes and risk of adverse neonatal and childhood outcomes following preterm premature rupture of membranes (PPROM). Study Design This is a secondary analysis of data from the Beneficial Effects of Antenatal Magnesium Sulfate Trial. Women with nonanomalous singletons and PPROM delivering >=24.0 weeks were included. Birthweight was classified as small for gestational age (SGA), appropriate for gestational age (AGA), or large for gestational age (LGA). Composite severe neonatal morbidity and childhood outcomes at age 2, were compared between these groups. Results One thousand five hundred and ninety-eight infants were included (58 SGA, 1,354 AGA, and 186 LGA). There was an inverse relationship between birthweight and rate of composite major neonatal morbidity (55.2% of SGA, 31.5% of AGA, 18.3% of LGA, p < 0.001). Former-SGA children were more likely to be diagnosed with major composite childhood morbidity at age 2 (25.9% of SGA, 8.3% of AGA, 5.9% of LGA, p < 0.001). In multivariate models, LGA infants had improved initial neonatal outcomes compared with AGA infants (adjusted odds ratio [aOR], 0.44; 95% confidence interval [CI], 0.28-0.71; p = 0.001). Conclusion Among infants delivered following PPROM, those who were LGA at delivery had improved composite adverse neonatal outcomes. SGA increases the risk of severe neonatal morbidity, early childhood death, and moderate/severe cerebral palsy at age 2. PMID- 27367281 TI - Birth Rates Among Hispanics and Non-Hispanics and their Representation in Contemporary Obstetric Clinical Trials. AB - Objective Our study aims were to establish whether subjects enrolled in current obstetric clinical trials proportionately reflects the contemporary representation of Hispanic ethnicities and their birth rates in the United States. Methods Using comprehensive source data over a defined interval (January 2011-September 2015) on birth rates by ethnicity from the Centers for Disease Control and Prevention (CDC), we evaluated the proportional rate by ethnicity, then analyzed the observed to expected relative ratio of enrolled subjects. Results Hispanic women comprise a significant contribution to births in the United States (23% of all births). Systematic analysis of 90 published obstetric clinical trials showed a correlation between inclusion of Hispanic gravidae and the corresponding state's birth rates (r = 0.501, p < 0.001). While the mean was strongly correlated, individual clinical trials may have relatively over-enrolled (n = 31, or 34%) or under-enrolled (n = 33, or 37%) relative to their regional population. In 48% of obstetric clinical trials the Hispanic proportion of the study population was not reported. Conclusion Hispanic gravidae represent a significant number of contemporary U.S. births, and are generally adequately represented as obstetric subjects in clinical trials. However, this is trial dependent, with significant trial-specific under- and over-enrollment of Hispanic subjects relative to the regional birth population. PMID- 27367282 TI - Meconium-Stained Amniotic Fluid and Neonatal Morbidity in Low-Risk Pregnancies at Term: The Effect of Gestational Age. AB - Objective To assess the association of gestational age at delivery with perinatal outcome in low-risk term deliveries complicated by meconium-stained amniotic fluid (MSAF). Methods We retrospectively analyzed all singleton deliveries that underwent a trial of labor in a single hospital (2007-2013). Exclusion criteria included pregnancy-related complications (e.g., hypertensive disorders, diabetes, oligohydramnios, and fetal anomalies). First, only deliveries with MSAF were analyzed. Perinatal outcome of deliveries at 370/7 to 386/7 weeks (early term) and 410/7 to 416/7 weeks (late term) were compared with those at 390/7 to 406/7 weeks of gestation (full term). Additionally, a gestational age based comparison was made between the risk for neonatal respiratory morbidity in deliveries with clear amniotic fluid and MSAF. Results During the study period, 28,248 deliveries were considered as low risk. Of them, 3,399 (12.0%) were diagnosed with MSAF and were divided to full term (n = 2,413), early term (n = 405), and late term (n = 581). In multivariate analysis, MSAF at early term was associated with neonatal jaundice, need for phototherapy, and neonatal sepsis. In a gestational age based stratification, when comparing between deliveries with clear amniotic fluid and those with MSAF, late term had the highest odds (4.2 vs. 0.5%; p < 0.001) for neonatal respiratory morbidity. Conclusion Gestational age was associated with specific complications in deliveries complicated by MSAF and otherwise low-risk deliveries. PMID- 27367283 TI - The Effect of Interpregnancy Interval on the Recurrence Rate of Spontaneous Preterm Birth: A Retrospective Cohort Study. AB - Objective We assessed, in women with a previous spontaneous preterm birth, the effect of interpregnancy interval on the subsequent preterm birth rate. Design Retrospective cohort study. Setting A nationwide longitudinal dataset of the the Netherlands Perinatal Registry. Population Women with three sequential singleton pregnancies between 1999 and 2009 and a spontaneous preterm birth <37 weeks in the first pregnancy. Methods We evaluated the impact of interpregnancy interval on the course of the next pregnancies. Antenatal death and/or congenital abnormalities were excluded. Conventional and conditional logistic regression analysis were applied. We adjusted for maternal age, ethnicity, socioeconomic status, artificial reproductive techniques, and year of birth. Main Outcome Measures Outcomes studied were preterm birth <37 weeks, <32 weeks, low birth weight <2500 g, and small for gestational age <10th percentile. Results Among 2,361 women with preterm birth in the first pregnancy, logistic regression analysis indicated a significant effect of a short interpregnancy interval (0-5 mo) on recurrent preterm birth <37 weeks (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.62-3.05), <32 weeks (OR, 2.90; 95% CI, 1.43-5.87), and low birth weight (OR, 2.69; 95% CI, 1.79-4.03). In addition, a long interval (>=60 mo) had a significant effect on preterm birth <37 weeks (OR, 2.19; 95% CI, 1.29-3.74). Conditional logistic regression analysis confirmed the effect of a short interval on the recurrence of preterm birth rate <37 weeks and low birth weight. Conclusion In women with a previous spontaneous preterm birth, a short interpregnancy interval has a strong impact on the risk of preterm birth before 37 weeks and low birth weight in the next pregnancy, irrespective of the type of analysis performed. PMID- 27367284 TI - Glycerin Suppositories Use in Very Low Birth Weight Infants. AB - Objective To study the characteristics of very low birth weight (VLBW) infants receiving glycerin suppositories (GS) and evaluate the association of GS use with outcomes. Study Design This is a retrospective study of VLBW infants admitted to a level III neonatal intensive care unit. Infants with birth weight between 500 and 1,499 g were evaluated. We evaluated the frequency of GS use and compared the characteristics and outcomes of the GS group with the no-GS group. Multivariate analyses controlling for gestational age and small for gestational age status were performed to study the effect of GS on outcomes. Results A total of 1,073 infants were included in the study. Out of those, 527 (49.1%) infants received GS. Incidence of necrotizing enterocolitis was not significantly different between the two groups, while days to reach full enteral feeds and length of hospital stay were significantly longer in the GS group. Conclusion Frequent use of GS warrants further prospective studies to evaluate its safety and efficacy in view of our study showing association with longer time to reach full enteral feeds. We speculate that GS use could be a marker for gastrointestinal dysmotility and hence the association with unfavorable clinical outcomes. PMID- 27367285 TI - Is There an Association Between Indication for Intrauterine Balloon Tamponade and Balloon Failure? AB - Objective Determine whether the indication for intrauterine balloon tamponade (IUBT) is associated with failure rates. Study Design Cohort study of women who underwent IUBT for postpartum hemorrhage (PPH) from 2007 to 2014. The indication was categorized as uterine atony or placental-site bleeding. Primary outcome was IUBT failure, defined as the need for uterine artery embolization or hysterectomy. Secondary outcomes were estimated blood loss (EBL) after balloon placement, transfusion of red blood cells (RBC), transfusion of fresh frozen plasma (FFP) and/or cryoprecipitate, and intensive care unit (ICU) admission. Results 306 women underwent IUBT: 241 (78.8%) for uterine atony and 65 (21.2%) for placental site bleeding. Overall, 67 (21.9%) women experienced IUBT failure. The frequency of failure was similar in those with uterine atony compared with those with placental-site bleeding (21.2 vs 24.6%, p = 0.55). This finding persisted after adjusting for potential confounders (aOR, 0.97; 95% CI, 0.48 1.99). Median EBL after balloon placement (190 [interquartile range, 93-375] vs 195 [interquartile range, 103-500] mL, p = 0.46), and frequencies of RBC transfusion (62.7 vs 66.2%, p = 0.60), FFP and/or cryoprecipitate transfusion (25.3 vs 33.8%, p = 0.17), and ICU admission (12.4 vs 16.9%, p = 0.35) were also similar. Conclusion IUBT was similarly effective for managing PPH from uterine atony or placental-site bleeding. PMID- 27367286 TI - Vascular endothelial growth factor polymorphism (-460 T/C) is related to hypertension-associated chronic kidney disease. AB - Our aim was to characterize the endothelial progenitor cells (EPCs) in normotensive controls and treated hypertensive individuals within the vascular endothelial growth factor (VEGF) -460 C/T polymorphism as well as to investigate whether this polymorphism predisposes to hypertension-related chronic kidney disease. The hypertensive patients bearing the TT genotype had the highest levels of immature EPC with the following phenotypes: CD34(+), CD34(+)CD45(dim), CD34(+)CD133(+)CD45(dim). The study showed the estimated glomerular filtration rate values significantly lower and creatinine and BUN parameters higher among the TT hypertensive patients. We presume that the highest mobilization of EPCs from bone marrow may signalize more severe renal hypertension-related complications in the VEGF -460 TT genotype. PMID- 27367287 TI - A Quantitative Method for Comparing the Brightness of Antibody-dye Reagents and Estimating Antibodies Bound per Cell. AB - We present a quantitative method for comparing the brightness of antibody-dye reagents and estimating antibodies bound per cell. The method is based on complementary binding of test and fill reagents to antibody capture microspheres. Several aliquots of antibody capture beads are stained with varying amounts of the test conjugate. The remaining binding sites on the beads are then filled with a second conjugate containing a different fluorophore. Finally, the fluorescence of the test conjugate compared to the fill conjugate is used to measure the relative brightness of the test conjugate. The fundamental assumption of the test fill method is that if it takes X molecules of one test antibody to lower the fill signal by Y units, it will take the same X molecules of any other test antibody to give the same effect. We apply a quadratic fit to evaluate the test fill signal relationship across different amounts of test reagent. If the fit is close to linear, we consider the test reagent to be suitable for quantitative evaluation of antibody binding. To calibrate the antibodies bound per bead, a PE conjugate with 1 PE molecule per antibody is used as a test reagent and the fluorescence scale is calibrated with Quantibrite PE beads. When the fluorescence per antibody molecule has been determined for a particular conjugate, that conjugate can be used for measurement of antibodies bound per cell. This provides comparisons of the brightness of different conjugates when conducted on an instrument whose statistical photoelectron (Spe) scales are known. (c) 2016 by John Wiley & Sons, Inc. PMID- 27367288 TI - High-Content Microscopy Analysis of Subcellular Structures: Assay Development and Application to Focal Adhesion Quantification. AB - High-content analysis (HCA) converts raw light microscopy images to quantitative data through the automated extraction, multiparametric analysis, and classification of the relevant information content. Combined with automated high throughput image acquisition, HCA applied to the screening of chemicals or RNAi reagents is termed high-content screening (HCS). Its power in quantifying cell phenotypes makes HCA applicable also to routine microscopy. However, developing effective HCA and bioinformatic analysis pipelines for acquisition of biologically meaningful data in HCS is challenging. Here, the step-by-step development of an HCA assay protocol and an HCS bioinformatics analysis pipeline are described. The protocol's power is demonstrated by application to focal adhesion (FA) detection, quantitative analysis of multiple FA features, and functional annotation of signaling pathways regulating FA size, using primary data of a published RNAi screen. The assay and the underlying strategy are aimed at researchers performing microscopy-based quantitative analysis of subcellular features, on a small scale or in large HCS experiments. (c) 2016 by John Wiley & Sons, Inc. PMID- 27367289 TI - Measurement and Characterization of Apoptosis by Flow Cytometry. AB - Apoptosis is an important mechanism in cell biology, playing a critical regulatory role in virtually every organ system. It has been particularly well characterized in the immune system, with roles ranging from immature immune cell development and selection to down-regulation of the mature immune response. Apoptosis is also the primary mechanism of action of anti-cancer drugs. Flow cytometry has been the method of choice for analyzing apoptosis in suspension cells for more than 25 years. Numerous assays have been devised to measure both the earliest and latest steps in the apoptotic process, from the earliest signal transduction events to the late morphological changes in cell shape and granularity, proteolysis, and chromatin condensation. These assays are particularly powerful when combined into multicolor assays determining several apoptotic characteristics simultaneously. The multiparametric nature of flow cytometry makes this technology particularly suited to measuring apoptosis. In this unit, we will describe the four main techniques for analyzing caspase activity in apoptotic cells, combined with annexin V and cell permeability analysis. These relatively simple multiparametric assays are powerful techniques for assessing cell death. (c) 2016 by John Wiley & Sons, Inc. PMID- 27367290 TI - Facile Construction of Random Gene Mutagenesis Library for Directed Evolution Without the Use of Restriction Enzyme in Escherichia coli. AB - A foolproof protocol was developed for the construction of mutant DNA library for directed protein evolution. First, a library of linear mutant gene was generated by error-prone PCR or molecular shuffling, and a linear vector backbone was prepared by high-fidelity PCR. Second, the amplified insert and vector fragments were assembled by overlap-extension PCR with a pair of 5'-phosphorylated primers. Third, full-length linear plasmids with phosphorylated 5'-ends were self-ligated with T4 ligase, yielding circular plasmids encoding mutant variants suitable for high-efficiency transformation. Self-made competent Escherichia coli BL21(DE3) showed a transformation efficiency of 2.4 * 10(5) cfu/ug of the self-ligated circular plasmid. Using this method, three mutants of mCherry fluorescent protein were found to alter their colors and fluorescent intensities under visible and UV lights, respectively. Also, one mutant of 6-phosphorogluconate dehydrogenase from a thermophilic bacterium Moorella thermoacetica was found to show the 3.5-fold improved catalytic efficiency (kcat /Km ) on NAD(+) as compared to the wild-type. This protocol is DNA-sequence independent, and does not require restriction enzymes, special E. coli host, or labor-intensive optimization. In addition, this protocol can be used for subcloning the relatively long DNA sequences into any position of plasmids. PMID- 27367291 TI - Effect of red mud addition on tetracycline and copper resistance genes and microbial community during the full scale swine manure composting. AB - Swine manure has been considered as the reservoir of antibiotic resistance genes (ARGs). Composting is one of the most suitable technologies for treating livestock manures, and red mud was proved to have a positive effect on nitrogen conservation during composting. This study investigated the abundance of eight tetracycline and three copper resistance genes, the bacterial community during the full scale swine manure composting with or without addition of red mud. The results showed that ARGs in swine manure could be effectively removed through composting (reduced by 2.4log copies/g TS), especially during the thermophilic phase (reduced by 1.5log copies/g TS), which the main contributor might be temperature. Additionally, evolution of bacterial community could also have a great influence on ARGs. Although addition of red mud could enhance nitrogen conservation, it obviously hindered removal of ARGs (reduced by 1.7log copies/g TS) and affected shaping of bacterial community during composting. PMID- 27367292 TI - Computational high-throughput screening of fluid permeability in heterogeneous fiber materials. AB - We explore computational high-throughput screening as a design strategy for heterogeneous, isotropic fiber materials. Fluid permeability, a key property in the design of soft porous materials, is systematically studied using a multi scale lattice Boltzmann framework. After characterizing microscopic permeability as a function of solid volume fraction in the microstructure, we perform high throughput computational screening of in excess of 35 000 macrostructures consisting of a continuous bulk interrupted by spherical/elliptical domains with either lower or higher microscopic permeability (hence with two distinct microscopic solid volume fractions and therefore two distinct microscopic permeabilities) to assess which parameters determine macroscopic permeability for a fixed average solid volume fraction. We conclude that the fractions of bulk and domains and the distribution of solid volume fraction between them are the primary determinants of macroscopic permeability, and that a substantial increase in permeability compared to the corresponding homogenous material is attainable. PMID- 27367294 TI - To Appear in CHEMICAL REVIEWS, Vol. 99, No. 5. PMID- 27367293 TI - Diagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline - Update 2016. AB - Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumour and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum, the European Association of Dermato Oncology and the European Organisation of Research and Treatment of Cancer was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. Diagnosis is made clinically using dermoscopy and staging is based upon the AJCC system. CMs are excised with 1-2 cm safety margins. Sentinel lymph node dissection is routinely offered as a staging procedure in patients with tumours >1 mm in thickness, although there is as yet no clear survival benefit for this approach. Interferon-alpha treatment may be offered to patients with stage II and III melanoma as an adjuvant therapy, as this treatment increases at least the disease-free survival and less clear the overall survival (OS) time. The treatment is however associated with significant toxicity. In distant metastasis, all options of surgical therapy have to be considered thoroughly. In the absence of surgical options, systemic treatment is indicated. For first-line treatment particularly in BRAF wild-type patients, immunotherapy with PD-1 antibodies alone or in combination with CTLA-4 antibodies should be considered. BRAF inhibitors like dabrafenib and vemurafenib in combination with the MEK inhibitors trametinib and cobimetinib for BRAF mutated patients should be offered as first or second line treatment. Therapeutic decisions in stage IV patients should be primarily made by an interdisciplinary oncology team ('Tumour Board'). PMID- 27367295 TI - Ledipasvir and sofosbuvir for HCV infection in patients coinfected with HBV. AB - BACKGROUND: Currently there are no all-oral treatment regimens for HCV in patients coinfected with HBV. In this pilot study, we evaluated whether ledipasvir and sofosbuvir therapy can suppress HCV infection in patients coinfected with HBV. METHODS: Patients with HBV and genotype-1 HCV received 90 mg ledipasvir and 400 mg sofosbuvir daily for 12 weeks. The efficacy end point was sustained virological response (HCV RNA <15 IU/ml) 12 weeks after the end of treatment. RESULTS: Of the eight patients enrolled, six (75%) were male, five (63%) were Polynesian, seven (88%) had the CC IL28B genotype and two (25%) had cirrhosis. All eight patients (100%; 95% CI 63%, 100%) reached the primary end point of HCV RNA <15 IU/ml 12 weeks after treatment. In seven of eight patients (88%), serum HBV DNA levels increased during treatment, but none of the increases were greater than 20,000 IU/ml, and none were associated with clinical HBV flares or required treatment. The most common adverse events were viral infection (63%), fatigue (25%) and upper respiratory tract infection (25%). No patients had serious adverse events and none discontinued treatment for any reason. CONCLUSIONS: In this small sample, 12 weeks of ledipasvir/sofosbuvir was a safe and effective treatment for genotype-1 HCV infection in patients coinfected with HBV. Larger studies with longer follow-up are warranted. PMID- 27367296 TI - Breast Cancer Genetic and Molecular Subtype Impacts Response to Omega-3 Fatty Acid Ethyl Esters. AB - Epidemiological studies have correlated frequent omega-3 (n-3) fatty acid consumption with a lower risk for breast cancer; however, recent prospective studies have been less conclusive. Efforts in the preventive setting have focused on the use of n-3 fatty acids, and the pharmaceutical ethyl esters (EE) of these natural compounds, for high-risk patient populations. Limited understanding of specific mechanisms by which these agents function has hampered identification of the cancer subtype(s) that would gain the greatest therapeutic benefit. In this study, we investigated the in vitro effects of n-3 EEs in four distinct breast cancer subtypes and explored how they affect not only breast cancer cell survival but also modulate the nuclear factor kappa-light-chain enhancer of activated B cells (NF-kappaB) and peroxisome proliferator-activated receptor gamma signaling pathways. Similar to the high variance in response observed in human studies, we found that the effectiveness of n-3 EEs depends on the molecular characteristics of the MCF-7, CAMA-1, MDA-MB-231, and SKBR3 breast cancer cell lines and is closely associated with the suppression of NF-kappaB. These data strongly suggest that the use of n-3 fatty acids and their pharmaceutical ether esters in the prevention and therapeutic setting should be guided by specific tumor characteristics. PMID- 27367297 TI - The safety of treatment options for pediatric Crohn's disease. AB - INTRODUCTION: A severe clinical phenotype along with concern for ensuring normal growth and development has a major impact on treatment choices for children newly diagnosed with Crohn's disease (CD). AREAS COVERED: We review the increasingly outdated concept of 'conventional' therapy of pediatric CD based on aminosalicylates, corticosteroids, and immunomodulators for patients at high risk of complicated disease. Key safety concerns with each treatment are reviewed. EXPERT OPINION: There are minimal data supporting the use of aminosalicylates in the treatment of pediatric CD. Corticosteroids are effective short-term for improving signs and symptoms of disease but are ineffective for maintenance therapy. Thiopurines decrease corticosteroid dependence but may not alter progression to complicated disease requiring surgery. Concerns for lymphoma as well as hemophagocytic lymphohistiocytosis with thiopurines are valid. Further data are required on the efficacy and safety of methotrexate as an alternative immunomodulator. Though generally well tolerated and efficacious in most patients, anti-TNF-alpha therapy can be associated with both mild as well as more serious complications. Current data do not support an increased risk for malignancy associated with anti-TNF therapy alone in children. Anti-adhesion therapy appears to have a favorable safety profile but the experience in children is extremely limited. PMID- 27367298 TI - ToxCast Chemical Landscape: Paving the Road to 21st Century Toxicology. AB - The U.S. Environmental Protection Agency's (EPA) ToxCast program is testing a large library of Agency-relevant chemicals using in vitro high-throughput screening (HTS) approaches to support the development of improved toxicity prediction models. Launched in 2007, Phase I of the program screened 310 chemicals, mostly pesticides, across hundreds of ToxCast assay end points. In Phase II, the ToxCast library was expanded to 1878 chemicals, culminating in the public release of screening data at the end of 2013. Subsequent expansion in Phase III has resulted in more than 3800 chemicals actively undergoing ToxCast screening, 96% of which are also being screened in the multi-Agency Tox21 project. The chemical library unpinning these efforts plays a central role in defining the scope and potential application of ToxCast HTS results. The history of the phased construction of EPA's ToxCast library is reviewed, followed by a survey of the library contents from several different vantage points. CAS Registry Numbers are used to assess ToxCast library coverage of important toxicity, regulatory, and exposure inventories. Structure-based representations of ToxCast chemicals are then used to compute physicochemical properties, substructural features, and structural alerts for toxicity and biotransformation. Cheminformatics approaches using these varied representations are applied to defining the boundaries of HTS testability, evaluating chemical diversity, and comparing the ToxCast library to potential target application inventories, such as used in EPA's Endocrine Disruption Screening Program (EDSP). Through several examples, the ToxCast chemical library is demonstrated to provide comprehensive coverage of the knowledge domains and target inventories of potential interest to EPA. Furthermore, the varied representations and approaches presented here define local chemistry domains potentially worthy of further investigation (e.g., not currently covered in the testing library or defined by toxicity "alerts") to strategically support data mining and predictive toxicology modeling moving forward. PMID- 27367299 TI - Can Cardiac Conduction System Disease Be Prevented? PMID- 27367300 TI - Does children's moral compass waver under social pressure? Using the conformity paradigm to test preschoolers' moral and social-conventional judgments. AB - The current study tested whether preschoolers' moral and social-conventional judgments change under social pressure using Asch's conformity paradigm. A sample of 132 preschoolers (Mage=3.83years, SD=0.85) rated the acceptability of moral and social-conventional events and also completed a visual judgment task (i.e., comparing line length) both independently and after having viewed two peers who consistently made immoral, unconventional, or visually inaccurate judgments. Results showed evidence of conformity on all three tasks, but conformity was stronger on the social-conventional task than on the moral and visual tasks. Older children were less susceptible to pressure for social conformity for the moral and visual tasks but not for the conventional task. PMID- 27367301 TI - The integration of visual context information in facial emotion recognition in 5- to 15-year-olds. AB - The current study investigated the role of congruent visual context information in the recognition of facial emotional expression in 190 participants from 5 to 15years of age. Children performed a matching task that presented pictures with different facial emotional expressions (anger, disgust, happiness, fear, and sadness) in two conditions: with and without a visual context. The results showed that emotions presented with visual context information were recognized more accurately than those presented in the absence of visual context. The context effect remained steady with age but varied according to the emotion presented and the gender of participants. The findings demonstrated for the first time that children from the age of 5years are able to integrate facial expression and visual context information, and this integration improves facial emotion recognition. PMID- 27367302 TI - Is Season of Birth Important for Multiple Sclerosis Risk? PMID- 27367303 TI - Early Detection of New Melanomas by Patients With Melanoma and Their Partners Using a Structured Skin Self-examination Skills Training Intervention: A Randomized Clinical Trial. AB - IMPORTANCE: More than 1 million patients with melanoma in the United States are at risk to develop a second primary melanoma. Early detection of melanoma improves survival. Patients with melanoma may be able to self-manage care with their skin-check partners ("partners") and alert the physician when a concerning lesion is identified, thus providing an important adjunct to yearly skin examinations by a physician. OBJECTIVE: To evaluate the effect of a structured skin self-examination (SSE) intervention for patients with melanoma and their partners ("dyads") on SSE performance and the detection of new melanomas by the dyad or the physician. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial with 24-month follow-up assessments. Patients with stage 0 to IIB melanoma and their skin-check partners participated from June 6, 2011, to April 24, 2015. INTERVENTIONS: Dyads of patients and their partners were randomly assigned to receive the skills training intervention or customary care (control group). MAIN OUTCOMES AND MEASURES: The main outcome was frequency of SSE performance. The secondary outcome was detection of a new or recurrent melanoma by the dyad or physician. The tertiary outcome was the number of unscheduled physician appointments for concerning lesions. RESULTS: The study cohort comprised 494 participants. The patient population was 51.2% (253 of 494) female and had a mean (SD) age of 55 (10) years. Patients in the intervention arms had significantly increased SSEs with their partners at 4, 12, and 24 months (P < .001 for all) compared with the control group (mean differences, 1.57 [95% CI, 1.29-1.85], 0.72 [95% CI, 0.39-1.06], and 0.94 [95% CI, 0.58-1.30], respectively). Patients in the intervention arms identified new melanomas more than those in the control group (chi21 = 28.77, P < .01 [n = 51 melanomas in situ] and chi21 = 6.43, P < .05 [n = 18 invasive melanomas]) and did not increase physician visits. CONCLUSIONS AND RELEVANCE: Patients with melanoma and their partners reliably performed SSE after participating in a structured skills training program lasting approximately 30 minutes, with reinforcement every 4 months by the study dermatologist. Accurate SSE by those at risk to develop melanoma may enhance early detection and relieve some of the burden on health services to provide continuing follow-up to a growing population of eligible patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01432860. PMID- 27367304 TI - Active Nanorheology with Plasmonics. AB - Nanoplasmonic systems are valued for their strong optical response and their small size. Most plasmonic sensors and systems to date have been rigid and passive. However, rendering these structures dynamic opens new possibilities for applications. Here we demonstrate that dynamic plasmonic nanoparticles can be used as mechanical sensors to selectively probe the rheological properties of a fluid in situ at the nanoscale and in microscopic volumes. We fabricate chiral magneto-plasmonic nanocolloids that can be actuated by an external magnetic field, which in turn allows for the direct and fast modulation of their distinct optical response. The method is robust and allows nanorheological measurements with a mechanical sensitivity of ~0.1 cP, even in strongly absorbing fluids with an optical density of up to OD ~ 3 (~0.1% light transmittance) and in the presence of scatterers (e.g., 50% v/v red blood cells). PMID- 27367305 TI - Correction to Novel Bispecific PSMA/GRPr Targeting Radioligands with Optimized Pharmacokinetics for Improved PET Imaging of Prostate Cancer. PMID- 27367306 TI - Mental disorders in adults with congenital heart disease: Unmet needs and impact on quality of life. AB - OBJECTIVE: In adult congenital heart disease (ACHD), mental health status and quality of life become important issues due to improved life expectancy. Current literature provides conflicting data regarding mental health status in ACHD. Furthermore, none of the studies so far compared prevalence rates with a matched control group. METHODS: The prevalence of mental disorders was assessed in 150 ACHD using a structured interview, and compared to 12-months estimates of the general German population. Quality of life (QoL) was measured with World Health Organization Quality of Life instrument. Furthermore, we related the diagnostic results of widely used screening instruments for depression (Beck Depression Inventory-2; BDI-2; Hospital Anxiety and Depression Scale; HADS) with clinical diagnoses, to receive optimal sensitivity and specificity values. RESULTS: The prevalence of psychiatric disorders was significantly higher in ACHD than in the general population (48.0%; CI: 44.7-60.0 vs. 35.7%; CI: 33.5-37.9). Mood (30.7%; CI: 24.0-38.0 vs. 10.7%;CI:9.4-12.0) and anxiety disorders (28.0%; CI:22.0-36.7 vs. 16.8%; CI: 15.0-18.6) were the leading causes of psychiatric illness. Sixteen of 150 ACHD patients (10.7%) received specific treatment for psychiatric disorders before entering the study. Overall quality of life was independently and negatively associated with a diagnosis of major depression (p<0.001), alcohol dependency (p=0.004), nicotine dependency (p=0.036), and NYHA class (p=0.007). Accuracy of the HADS-D and BDI-2 as screening instruments was moderate (AUC 0.60 0.81), depending on the cut-off score used. CONCLUSIONS: Psychiatric disorders, particularly mood and anxiety disorders are significantly more frequent in ACHD compared to the general population. However, these disorders are rarely diagnosed resulting in under treatment and loss of quality of life. Quality of life is independently associated with the existence of mood, anxiety and substance use disorders. When self-rating instruments (BDI-2, HADS) are used as screening instruments in ACHD care, lower cut-off values are recommended. PMID- 27367307 TI - Relative hypocortisolism is associated with obesity and the metabolic syndrome in recurrent affective disorders. AB - BACKGROUND: Cardiovascular disease (CVD) is one of the main causes of excess deaths in affective disorders. Affective disorders are associated with increased frequencies of CVD risk-factors such as obesity, dyslipidemia, and metabolic syndrome. Stress-induced chronic cortisol excess has been suggested to promote obesity and metabolic syndrome. Chronic stress with frequent or persisting hypothalamic-pituitary-adrenal-axis (HPA-axis) hyperactivity may, over time, lead to a state of low HPA-axis activity, also denoted hypocortisolism. A low-dose weight-adjusted dexamethasone-suppression-test (DST) is considered to be a sensitive measure of hypocortisolism. METHODS: 245 patients with recurrent depression or bipolar disorder and 258 controls participated in a low-dose DST and were also examined with regard to metabolic status. RESULTS: Patients with hypocortisolism (low post-DST cortisol) compared with patients without hypocortisolism (normal or high post-DST cortisol) exhibited increased odds ratios (OR) for obesity (OR=4.0), overweight (OR=4.0), large waist (OR=2.7), high LDL (OR=4.2), low HDL (OR=2.4), high LDL/HDL ratio (OR=3.3), high TC/HDL ratio (OR=3.4) and metabolic syndrome (OR=2.0). A similar pattern but less pronounced was also found in the control sample. LIMITATIONS: The cross sectional study design and absence of analyses addressing lifestyle factors. CONCLUSIONS: Our findings suggest that a substantial portion of the metabolic disorders and cardiovascular risk factors seen in recurrent affective disorders are found among individuals exhibiting hypocortisolism. This might indicate that long-term stress is a central contributor to metabolic abnormalities and CVD mortality in recurrent affective disorders. PMID- 27367308 TI - Positive beliefs about mental illness: Associations with sex, age, diagnosis, and clinical outcomes. AB - BACKGROUND: Beliefs about mental illness affect how individuals cope with their symptoms. Positive beliefs about mental illness (PBMI) refer to perceptions of positive attributes individuals may identify in their illness, such as beneficial consequences, enhanced creativity or cognition, or growth through adversity. METHODS: The present study developed and tested a brief measure of PBMI in 332 adults presenting for partial hospitalization with a variety of acute psychiatric conditions. RESULTS: Results indicated that older individuals and women had lower levels of PBMI than others, while individuals with bipolar disorder had higher levels of PBMI than others. PBMI significantly increased over the course of brief standard treatment. Baseline levels of PBMI, as well as changes in PBMI over the course of treatment, were associated with clinical outcomes including, but not limited to, depression and well-being. A diagnosis of bipolar disorder moderated the relationship between PBMI and only one clinical outcome, emotional lability. Increases in PBMI during treatment were associated with reduced emotional lability only in participants without bipolar disorder. LIMITATIONS: Our findings are limited by the naturalistic study design. In addition, the lack of ethnoracial diversity in our sample limits the generalization of results. CONCLUSIONS: Our results suggest that PBMI are a distinct set of beliefs that meaningfully relate to demographic characteristics, diagnostic characteristics, and clinical outcomes. Future research should examine the mechanisms through which PBMI and outcomes are related, as well as determine whether interventions designed to address PBMI (and perhaps tailored for different diagnostic groups) have clinical utility. PMID- 27367310 TI - Health Insurance for Emergency Hospitalization-Isn't the Point to Pay the Bill? PMID- 27367309 TI - Validation of a qualitative immunochromatographic test for the noninvasive assessment of stress in dogs. AB - Salivary cortisol is regarded as a reliable parameter for the noninvasive assessment of the welfare of animals, because it is strictly related to stress levels. Several methods are available for salivary cortisol measurement in mammals, however rapid diagnostic test for detecting salivary cortisol are confined to humans. The availability of such non invasive diagnostic tools operable in situ would facilitate monitoring of animal welfare. The Cortisol stressTM test provides a simple and rapid tool to discriminate cortisol levels in canine saliva above or below 4ng/ml, which has been suggested as the cut-off value for distinguishing unstressed dogs from those experiencing stress. The test is based on a competitive immunochromatographic assay (ICT) using gold nanoparticles as probes, in which the color intensity of the Test line is inversely correlated to the salivary cortisol level. The qualitative result is obtained by the visual observation of the color formed on the Test line compared to that of the Control line We evaluated the accuracy of the test by determining salivary cortisol in 85 samples of canine saliva belonging to dogs with very variable age, sex, breed, and life history, and comparing the qualitative results to those obtained by a reference ELISA kit. Agreeing results were obtained through the two methods, and the ICT showed high diagnostic sensitivity, specificity and efficiency (100%, 98.4%, and 98.8%, respectively). Furthermore, we evaluated the precision of the test by an experimental design approach, which combines errors due to within-day and between-day variation with the biological variability, and demonstrated that the test could be reliably applied for correctly classifying canine samples, according to their salivary cortisol level. Moreover, we studied the shelf-life of the device in three experimental conditions. We confirmed the stability of the ICT at 4 degrees C and 25 degrees C for at least six months and observed similar results for an accelerated stability study conducted for 7days at 37 degrees C, which suggest that the stability of ICT device could be estimated by the accelerated experiment alternatively to the real-time study. PMID- 27367311 TI - Role of Contrast in MR Imaging. AB - Magnetic resonance (MR) contrast agents have been widely used over the last 3 decades in routine clinical practice. Paul Lauterbur recognized the presence of these contrast agents, which act as paramagnetic catalysts that accelerate the T1 relaxation process. The first MR contrast agent to be approved for clinical use was in 1988, and since then, it is estimated that 200 million doses have been administered worldwide. These contrast agents have diverse clinical as well as research applications, involving almost all the body organs. This review will cover some existing as well as many new applications that have emerged over the last few decades. MR imaging now has the potential of being used to monitor enzymatic activity, gene expression, metal ion homeostasis, and cell death in vivo. In future, newer contrast agents will develop and become commercially available, expanding the current clinical applications of MR contrast media. PMID- 27367312 TI - Alternatives to GBCA: Are We There Yet? AB - Gadolinium has been widely used as the contrast agent of choice for magnetic resonance imaging (MRI). However, gadolinium administration is not always desired due to its inherent enhancement properties and potential side effects (nephrogenic systemic fibrosis). This article reviews gadolinium alternatives, iron-, and manganese- based agents, and their current clinical usage for contrast enhanced MRI examinations. PMID- 27367313 TI - MRI Contrast Agents: Evolution of Clinical Practice and Dose Optimization. AB - Accurate detection of lesions throughout the body is of paramount importance in contrast-enhanced magnetic resonance imaging (MRI). Optimal contrast agent performance is therefore of great importance and given the number of MRI contrast agent options today, this topic is of much ongoing study. The goal of this review article is to bring the read up to date on pertinent articles that relate to the evolution of radiological clinical practice and dose optimization pertaining to gadolinium contrast agents. PMID- 27367314 TI - Adverse Effects of Gadolinium-Based Contrast Agents: Changes in Practice Patterns. AB - Gadolinium-based contrast agents have been used for magnetic resonance imaging (MRI) examinations since the late 1980s with an excellent overall cumulative safety record. Initially favored for use in patients with renal impairment because of lack of significant nephrotoxic effect at clinical doses, in 2006, multiple reports convincingly linked the rare but serious disease nephrogenic systemic fibrosis to the administration of gadolinium-based contrast agents in patients with severe renal failure. This in turn led to new policies on administration of these agents, resulting in changes in practice patterns that have virtually resulted in the elimination of the disease after the year 2009. The purpose of this review is to summarize the factors that led to the emergence of nephrogenic systemic fibrosis, including the risk associated with different types of contrast agents based on their stability, and the changes in practice patterns and usage of gadolinium-based contrast agents in recent years that have been mainly driven by the discovery and association with nephrogenic systemic fibrosis. The article will conclude with a brief overview of new emerging safety concerns that could further impact the use of this class of contrast agents and impact practice patterns in the future. PMID- 27367315 TI - MRI Contrast Agents: Update on Clinical Trial Data and Impact on Current Practice. PMID- 27367317 TI - Identification and functional characterization of EseH, a new effector of the type III secretion system of Edwardsiella piscicida. AB - Edwardsiella piscicida, a bacterial pathogen in fish and humans, expresses a type III secretion system (T3SS) that is critical for pathogen virulence and disease development. However, little is known about the associated effectors and their functional importance. In this study, we identified the ETAE_1757 encoded protein, termed here E. piscicida secretion effector H (EseH) as a novel T3SS effector. We found that upon infection with E. piscicida, EseH is translocated into nucleus of host cells which required the T3SS. Homology modelling analysis suggests that EseH is an enzyme that belongs to the family of phosphothreothine lyases. Consistently, EseH inhibited phosphorylation of ERK1/2, p38alpha and JNK MAPK pathways in host cells, but had no effect on the NF-kB pathway. Furthermore, mutation of the critical amino acid residues predicted to confer phosphothreonine lyase activity abolished the ability of EseH to inhibit phosphorylation of ERK1/2, p38alpha and JNK MAPK pathways in host cells. In addition, we found an increase in transcript levels of TNF-alpha, IL-12, IL-10 and IFN-gamma in zebrafish infected with the eseH mutant when compared with the wild type bacterium. Importantly, the virulence of E. piscicida deficient in EseH was highly attenuated in the zebrafish infection model which correlated with decreased loads of the mutant bacterium in both liver and kidney. Complementation of the E. piscicida mutant strain with EseH restored virulence in zebrafish. These results identified EseH as a critical T3SS effector that contributes to virulence by targeting MAPK signalling during E. piscicida infection. PMID- 27367318 TI - Climate, environment and transmission of malaria. AB - Malaria, the most common parasitic disease in the world, is transmitted to the human host by mosquitoes of the genus Anopheles. The transmission of malaria requires the interaction between the host, the vector and the parasite.The four species of parasites responsible for human malaria are Plasmodium falciparum, Plasmodium ovale, Plasmodium malariae and Plasmodium vivax. Occasionally humans can be infected by several simian species, like Plasmodium knowlesi, recognised as a major cause of human malaria in South-East Asia since 2004. While P. falciparum is responsible for most malaria cases, about 8% of estimated cases globally are caused by P. vivax. The different Plasmodia are not uniformly distributed although there are areas of species overlap. The life cycle of all species of human malaria parasites is characterised by an exogenous sexual phase in which multiplication occurs in several species of Anopheles mosquitoes, and an endogenous asexual phase in the vertebrate host. The time span required for mature oocyst development in the salivary glands is quite variable (7-30 days), characteristic of each species and influenced by ambient temperature. The vector Anopheles includes 465 formally recognised species. Approximately 70 of these species have the capacity to transmit Plasmodium spp. to humans and 41 are considered as dominant vector capable of transmitting malaria. The intensity of transmission is dependent on the vectorial capacity and competence of local mosquitoes. An efficient system for malaria transmission needs strong interaction between humans, the ecosystem and infected vectors. Global warming induced by human activities has increased the risk of vector-borne diseases such as malaria. Recent decades have witnessed changes in the ecosystem and climate without precedent in human history although the emphasis in the role of temperature on the epidemiology of malaria has given way to predisposing conditions such as ecosystem changes, political instability and health policies that have reduced the funds for vector control, combined with the presence of migratory flows from endemic countries. PMID- 27367316 TI - Binge-Eating Disorder in Adults: A Systematic Review and Meta-analysis. AB - BACKGROUND: The best treatment options for binge-eating disorder are unclear. PURPOSE: To summarize evidence about the benefits and harms of psychological and pharmacologic therapies for adults with binge-eating disorder. DATA SOURCES: English-language publications in EMBASE, the Cochrane Library, Academic OneFile, CINAHL, and ClinicalTrials.gov through 18 November 2015, and in MEDLINE through 12 May 2016. STUDY SELECTION: 9 waitlist-controlled psychological trials and 25 placebo-controlled trials that evaluated pharmacologic (n = 19) or combination (n = 6) treatment. All were randomized trials with low or medium risk of bias. DATA EXTRACTION: 2 reviewers independently extracted trial data, assessed risk of bias, and graded strength of evidence. DATA SYNTHESIS: Therapist-led cognitive behavioral therapy, lisdexamfetamine, and second-generation antidepressants (SGAs) decreased binge-eating frequency and increased binge-eating abstinence (relative risk, 4.95 [95% CI, 3.06 to 8.00], 2.61 [CI, 2.04 to 3.33], and 1.67 [CI, 1.24 to 2.26], respectively). Lisdexamfetamine (mean difference [MD], -6.50 [CI, -8.82 to -4.18]) and SGAs (MD, -3.84 [CI, -6.55 to -1.13]) reduced binge eating-related obsessions and compulsions, and SGAs reduced symptoms of depression (MD, -1.97 [CI, -3.67 to -0.28]). Headache, gastrointestinal upset, sleep disturbance, and sympathetic nervous system arousal occurred more frequently with lisdexamfetamine than placebo (relative risk range, 1.63 to 4.28). Other forms of cognitive behavioral therapy and topiramate also increased abstinence and reduced binge-eating frequency and related psychopathology. Topiramate reduced weight and increased sympathetic nervous system arousal, and lisdexamfetamine reduced weight and appetite. LIMITATIONS: Most study participants were overweight or obese white women aged 20 to 40 years. Many treatments were examined only in single studies. Outcomes were measured inconsistently across trials and rarely assessed beyond end of treatment. CONCLUSION: Cognitive behavioral therapy, lisdexamfetamine, SGAs, and topiramate reduced binge eating and related psychopathology, and lisdexamfetamine and topiramate reduced weight in adults with binge-eating disorder. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. PMID- 27367319 TI - Listeria monocytogenes meningitis in the elderly: epidemiological, clinical and therapeutic findings. AB - Listeria monocytogenes is a Gram-positive bacillus and facultative intracellular bacterium whose transmission occurs mainly through the consumption of contaminated food, L. monocytogenes invades the host cells using various protein and can escape to the human T-cell immune system by cell-to-cell spreading. If the infection is not controlled at the stage in which the bacterium is in the liver, for instance, due to a severe immunodepression, a secondary bacteraemia can be developed and L. monocytogenes reaches the preferred sites transgressing the blood-brain barrier or the placental barrier. Individuals with T-cell dysfunction, such as pregnant women, the elderly, and those receiving immunosuppressive therapy are at the highest risk of contracting the disease. Average life expectancy throughout developed countries has rapidly increased during the latter half of the 20th century and geriatric infectious diseases have become an increasingly important issue. L. monocytogenes meningitis in young previously healthy adults has been reported only in anecdotal observations. Differently, L. monocytogenes is the third most common cause of bacterial meningitis in the elderly population, after Streptococcus pneumoniae and Neisseria meningitidis. Patients with L. monocytogenes meningitis presented with signs and symptoms that were similar to those of the general population with community-acquired bacterial meningitis, but reported a longer prodromal phase. According to literature data, the prevalence of the classic triad of fever, neck stiffness, and altered mental status is 43%, and almost all patients present with at least 2 of the 4 classic symptoms of headache, fever, neck stiffness, and altered mental status. On the basis of our published data, in patients aged over 50 years, diagnosing L. monocytogenes meningitis was more challenging than pneumococcal meningitis, as demonstrated by the lower percentage of cases receiving a correct diagnosis within 48 hours from the onset of symptoms. No significant difference was observed in respect to the presenting symptoms, but progression to respiratory failure was not as rapid as pneumococcal meningitis. PMID- 27367320 TI - Molecular sensitivity threshold of wet mount and an immunochromatographic assay evaluated by quantitative real-time PCR for diagnosis of Trichomonas vaginalis infection in a low-risk population of childbearing women. AB - Vaginal trichomoniasis is a sexually transmitted infection caused by Trichomonas vaginalis, a flagellated protozoan. Diagnosis of T. vaginalis infection is mainly performed by wet mount microscopy, with a sensitivity ranging from 38% to 82%, compared to culture, still considered the gold standard. Commercial immunochromatographic tests for monoclonal-antibody-based detection have been introduced as alternative methods for diagnosis of T. vaginalis infection and have been reported in some studies to be more sensitive than wet mount. Real-time PCR methods have been recently developed, with optimal sensitivity and specificity. The aim of this study was to evaluate whether there is a molecular sensitivity threshold for both wet mount and imunochromatographic assays. To this aim, a total of 1487 low-risk childbearing women (median age 32 years, interquartile range 27-37) were included in the study, and underwent vaginal swab for T. vaginalis detection by means of a quantitative real-time PCR assay, wet mount and an immunochromatographic test. Upon comparing the results, prevalence values observed were 1.3% for real-time PCR, 0.5% for microscopic examination, and 0.8% for the immunochromatographic test. Compared to real-time PCR, wet mount sensitivity was 40% (95% confidence interval 19.1% to 63.9%) and specificity was 100% (95% CI 99.7% to 100%). The sensitivity and specificity of the immunochromatographic assay were 57.9% (95% CI 33.5% to 79.8%) and 99.9% (95% CI 99.6% to 100%), respectively. Evaluation of the wet mount results and those of immunochromatographic assay detection in relation to the number of T. vaginalis DNA copies detected in vaginal samples showed that the lower identification threshold for both wet mount (chi-square 6.1; P = 0.016) and the immunochromatographic assay (chi-square 10.7; P = 0.002) was >=100 copies of T. vaginalis DNA/5 mcl of eluted DNA. PMID- 27367321 TI - An analysis of children with brucellosis associated with haemophagocytic lymphohistiocytosis. AB - This retrospective study included seven paediatric cases aged from 4 to 14 (10.2+/-3.4) years with pathologically proved haemophagocytic lymphohistiocytosis from a single institution during 2009 and 2013. Over this time period, 496 patients with brucellosis were diagnosed. None of the patients (3 boys and 4 girls) had a history of any haematologic disorder. All patients had an anamnesis for recently consumed unpasteurised homemade dairy products or had a contact history with sheep and/or cows. The diagnosis of brucellosis was confirmed by standard tube agglutination test in all patients; titres were 1: 1280 in seven patients. Blood culture was positive for Brucella melitensis in three patients (42%). Bone marrow cultures were positive for B. melitensis in four patients (57%). Fever was present in all patients (100%) with haemophagocytic lymphohistiocytosis. The other most common symptoms were malaise, myalgia, anorexia, sweating and weight loss. In addition, sweating was observed in five patients, and lymphadenopathy, petechiae, and weight loss were observed in one patient. Hepatomegaly, splenomegaly, and hepatosplenomegaly were found in four (57%), six (85%) and four (57%), patients, respectively. Haemophagocytosis was documented in bone marrow examinations of all children except in two cases. All patients recovered completely, and their peripheral blood counts returned to normal by 2 to 4 weeks after antibiotic treatment of brucellosis. PMID- 27367322 TI - Metabolic syndrome as an independent risk factor of hypoxaemia in influenza A (H1N1) 2009 pandemic. AB - A swine-origin influenza A (H1N1) emerged as a pandemic in 2009. We investigated the association between the overweight, metabolic syndrome and the severity of disease in the confirmed cases in Qazvin province, Iran. The study sample included all patients over 12 years old with confirmed influenza A (H1N1) in the province of Qazvin, Iran, in the 2009 pandemic, excluding pregnant women. To define overweight, sex and age-specific body mass index (BMI) cutoffs recommended by the International Obesity Task Force were used. Metabolic syndrome was defined by ATP III criteria. Multiple logistic regression analysis was performed to identify statistically independent predictors of hypoxaemia. Out of 55 confirmed cases, 28 (50.9%) were overweight and 24 (45.3%) were identified as having metabolic syndrome by ATP III criteria. Twenty four patients had hypoxaemia (arterial oxygen saturation below 90%) during the course of the disease. In multivariate logistic regression analysis, pulmonary co-morbidity (OR=9.54; 95% CI, 1.36 to 66.88; p= 0.023) and the metabolic syndrome (OR=18.66; 95% CI, 1.60 to 217.47; p= 0.019) were revealed to be independent risk factors for hypoxaemia in influenza A (H1N1) pdm09. The results of the present study reveal the role of the metabolic syndrome on the severity of influenza A (H1N1) pdm09 infection. PMID- 27367323 TI - Infections of cardiovascular implantable electronic devices: 14 years of experience in an Italian hospital. AB - The aim of the study was to describe the microbial aetiology of infections from cardiovascular implantable electronic devices (CIEDs) between 2001 and 2014 at The Centro Cuore Morgagni Hospital (Catania, Italy). In this 14-year retrospective study on pacemaker isolates 1,366 patients were evaluated and clinical data were collected. CIEDs were analyzed and isolates tested by routine microbiological techniques. The presence of bacterial biofilm was assessed by means of scanning electron microscopy. Of the patients, fifty-three had catheter related infections (3.9%), mainly resulting from Staphylococci (4 S. aureus, 32 S. epidermidis, 15 S. hominis, 3 S. haemolyticus, 1 S. warnerii, 1 S. schleiferi, 1 S. lentus and 1 S. capitis) that covered the cardiac catheter with biofilm. Overall, oxacillin-resistance was 55.1%, especially among S. epidermidis, while all isolates were susceptible to vancomycin, teicoplanin, tigecyclin, rifampin, trimethoprim/sulfamethoxazole, linezolid, moxifloxacin, tobramycin and gentamicin. Coagulase-negative staphylococci were the most frequently isolated and S. epidermidis was largely the main single agent. Only four Gram negatives caused polymicrobial infections with Staphylococci. Despite improvements in CIED design and implantation techniques, infection of cardiac devices remains a serious problem. PMID- 27367324 TI - Changing modalities of outpatient parenteral antimicrobial therapy use over time in Italy: a comparison of two time periods. AB - This study aimed to assess the extent and nature of recent changes in the management of outpatient parenteral antimicrobial therapy (OPAT) in Italy. We reviewed our previously reported data from 1999 to 2003 and compared them with data from patients who received OPAT from 2005 to 2010. Data for 1175 patients who received OPAT were analysed. Skin and soft tissue infections (SSTIs) were the most common infection treated with OPAT in both time periods, but an increase in patients with SSTIs receiving OPAT was observed. By contrast, a decline over time of OPAT use was found for patients affected by pneumonia. Furthermore, ceftriaxone use declined, whereas teicoplanin increased over time. In conclusion, OPAT use has significantly changed over time in Italy. PMID- 27367325 TI - Tick-related facial cellulitis caused by Francisella tularensis. AB - Tick-borne illnesses have diverse biological and clinical features that make recognition and appropriate treatment challenging. Arthropod-transmitted (ticks, fleas and deer flies) tularaemia remains a concern worldwide. Generally, two kinds of tularaemia manifestations, namely ulceroglandular and glandular infections, can arise from the bite of an infected arthropod vector. If the ulceroglandular or glandular form is not treated, suppuration can arise from the gland. In addition, cellulitis is rarely observed around the ulcers. In our case, with the knowledge of tick exposure to the scalp, tularaemia was not initially considered for facial cellulitis without regional lymphadenopathy and also due to apparent failure to respond to doxycycline and gentamicin therapy. Serological confirmation in the late stages of the disease suggests the importance of clinical suspicion in such rare conditions. PMID- 27367326 TI - HBsAg seroconversion after pegylated interferon alfa 2a rescue in a lamivudine resistant patient with HBeAg-negative chronic hepatitis B and favourable IL28-B genotype. AB - Hepatitis B virus (HBV) surface antigen (HBsAg) seroconversion to anti-HBs antibody is the best final objective for all available chronic hepatitis B (CHB) treatments. Unfortunately, this goal is rarely achieved with the currently applied therapeutic approaches. Here we describe the case of an anti-HBe-positive CHB patient who was successfully treated with a particular therapeutic schedule. The patient was initially treated with lamivudine (LAM) for nine years. Breakthrough was observed after eight years of LAM therapy. HBV-DNA was 3x10E4 IU/mL and LAM resistance mutations were present. Subcutaneous pegylated interferon (PEG-IFN) alfa 2a, 180 mcg/week, was added to LAM and after 4 weeks LAM was discontinued and PEG-IFN alone was continued up to week 52. HBV-DNA became undetectable at week 4 of therapy; serum HBsAg started to decline from week 4 and became undetectable at week 36, with the subsequent appearance of anti HBs antibodies. IL28-B was genotyped at the polymorphic site rs12979860 and the CC allele was detected. Rescue therapy with Peg-IFN may be an option for selected patients with resistance to nucleos(t)ide analogues. PMID- 27367327 TI - Diagnosis of Nocardia paucivorans central nervous system infection by DNA sequencing from paraffin-embedded tissue. AB - Infections by Nocardia spp. are generally regarded as opportunistic diseases in immunocompromised patients, but can also affect immunocompetent subjects. Such infections represent an important diagnostic challenge for clinicians and microbiologists, and diagnosis is frequently delayed or even conducted post mortem. A 54-year-old man was admitted to our hospital because of ventriculitis and relapsing brain abscess. Five months prior, this patient had undergone external ventricular drain and surgery for a cerebellar abscess. Histopathology demonstrated pyogenic inflammatory reaction, microbiologic investigations proved negative and empiric antimicrobial therapy was administered for a total of eight weeks. Six weeks later, the patient developed relapsing neurologic manifestations. On reviewing the patient's clinical history it emerged that the patient had suffered pneumonia two months prior to neurosurgery, treated with amoxicillin/clavulanate 3g a day and levofloxacin 500mg a day for three weeks. On the CNS relapsing manifestations, nocardiosis was suspected and DNA sequencing from the formalin-fixed paraffin-embedded cerebellar tissue collected during neurosurgery allowed diagnosis of Nocardia paucivorans infection. The patient received medical therapy for 11 months. At follow-up, eight months after treatment was discontinued, the patient was aymptomatic. Nocardia spp. infections need to be suspected not only in immunocompromised, but also in immunocompetent patients. Proper samples need to be collected for proper microbiologic investigations. Paraffin-embedded tissue genomic sequencing can be a useful tool for diagnosis of nocardiosis. PMID- 27367328 TI - Pulmonary infection caused by Talaromyces purpurogenus in a patient with multiple myeloma. AB - A 66-year-old female patient with multiple myeloma (MM) was admitted to the emergency service on 29.09.2014 with an inability to walk, and urinary and faecal incontinence. She had previously undergone autologous bone marrow transplantation (ABMT) twice. The patient was hospitalized at the Department of Haematology. Further investigations showed findings suggestive of a spinal mass at the T5-T6 T7 level, and a mass lesion in the iliac fossa. The mass lesion was resected and needle biopsy was performed during a colonoscopy. Examination of the specimens revealed plasmacytoma. The patient also had chronic obstructive pulmonary disease (COPD) and was suffering from respiratory distress. After consultation with an infectious diseases specialist the patient was placed on an intravenous antibiotherapy with piperacillin/tazobactam (4.5g x 3) on 17.10.2014. During piperacillin/tazobactam treatment, the patient suffered from drowsiness, her general condition deteriorated, and she had rales on auscultation of the lungs. The patient underwent thoracic computerized tomography (CT) which showed areas of focal consolidation in the lower lobes of the two lungs (more prominent on the left), and increased medullary density. The radiology report suggested that fungal infection could not be ruled out based on the CT images. The sputum sample was sent to the mycology laboratory and direct microscopic examination performed with Gram and Giemsa staining showed the presence of septate hyphae; therefore voriconazole was added to the treatment. Slow growing (at day 10), grey-greenish colonies and red pigment formation were observed in all culture media except cycloheximide-containing Sabouraud dextrose agar (SDA) medium. The isolate was initially considered to be Talaromyces marneffei. However, it was subsequently identified by DNA sequencing analysis as Talaromyces purpurogenus. The patient was discharged at her own wish, as she was willing to continue treatment in her hometown. Unfortunately, the patient died on December 8, 2014. In conclusion, apart from T. marneffei, less common strains such as T. purpurogenus should be considered when clinical samples obtained from patients with haematologic/oncologic disorders show fungal colonies that form red pigments on the culture media and when microscopic examination suggests a morphological appearance similar to Penicillium species. PMID- 27367329 TI - The Poet and the Disease. AB - Ugo Foscolo, was an Italian writer, revolutionary and poet whose works rank among the masterpieces of Italian literature. Talented and well educated in philosophy, classics and Italian literature, Foscolo gave literary expression to his ideological aspirations and to his numerous amorous experiences in odes, sonnets, plays, poems and an epistolary novel. Concurrent with his rich literary output, Foscolo's correspondence represents a unique perspective from which to monitor his literary and political views and investigate aspects of his everyday life. Among other interesting information, one can find elements of Foscolo medical history which is generally unknown. In the present article we investigate the longstanding lower urinary tract symptoms as reported by the poet in his correspondence to his family and friends. PMID- 27367330 TI - Pestilence, riots, lynchings and desecration of corpses. The sleep of reason produces monsters. AB - Vampirism has been a component of Central European and Balkan folklore since the Middle Ages and was often believed to be responsible for the transmission of serious infectious diseases such as plague and tuberculosis/consumption. Vampirism was believed to be spread within the same family or village and if the rite of the so-called second burial after death was not performed. The practice of "second burial" entailed exhumation of the body and the removal of the shroud from the mouth of the corpse, and a search for evidence if the corpse had chewed the cloth. If the shroud was chewed, a handful of earth or a brick was put into the body's mouth so that the vampire could no longer harm others. In some cases, the corpse was decapitated and an awl, made of ash, was thrust into its chest. Furthermore, the limbs were nailed down to prevent its movements. Remarkably, these beliefs were not restricted to the popular classes, but were also debated by theologians, political scientists at the height of the eighteenth century (Enlightenment). In the Habsburg Empire, this question attained such important political, social as well as health connotations as to force the Empress Maria Theresa to entrust an ad hoc study to her personal physician Gerard van Swieten with a view to determining what was true about the apparitions of vampires that occurred throughout central Europe and in the Balkans. The result of this investigation led to a ban on the "second burial" rites. Despite this prohibition, the practice of necrophilia on the bodies of suspected people continued, and both a cultured and popular literature on vampirism continued to flourish well into the nineteenth century. PMID- 27367331 TI - The outbreak of Zika virus in the Americas: actions and challenges in Peru. AB - Not available. PMID- 27367332 TI - Chikungunya: another urological disease? AB - Not available. PMID- 27367333 TI - Erratum: Circulating Apo 2L levels decreased in genotype II hepatitis C with pegylated interferon-2 alpha treatment. AB - Erratum Following publication of the original article (Le Infezioni in Medicina, 2014, vol:22 (4):pp:283-287) we became aware of the following errors in Table 1 and Figure 1 which we wish to correct. These corrections have no impact over the study results, their interpretation or conclusions. PMID- 27367334 TI - Methemoglobinemia from frozen-dried mudfish contaminated with sodium nitrite. PMID- 27367335 TI - Post-traumatic stress disorder symptoms and associated health and social vulnerabilities in older jail inmates. AB - OBJECTIVES: To examine post-traumatic stress disorder (PTSD) symptoms in older jail inmates, and to determine whether adverse social and health-related characteristics were associated with having PTSD symptoms. METHOD: We performed an exploratory cross-sectional study of 238 older (age >=55 years) jail inmates from a county jail. PTSD symptoms were determined using the Primary Care PTSD (PC PTSD) screen. Reporting three or more PTSD symptoms was defined as a positive screen. Descriptive statistics and multiple regression analyses were used to examine the prevalence of a positive PTSD screen and associations with social and health-related characteristics. RESULTS: The mean age was 59 years, 64% were Black, and 82% reported an annual income <=$15,000. Nearly 40% of older jail inmates had a positive PTSD screen and 10% reported a prior PTSD diagnosis by a physician. Older jail inmates with a positive PTSD screen were significantly more likely than those with a negative PTSD screen to report medication insecurity in the past year, impairment in two or more activities of daily living, traumatic brain injury, pain in the past week, and poor self-rated health. CONCLUSION: Over one in three of the older jail inmates in this study had a positive PTSD screen, though only one in five of those with a positive screen reported a prior PTSD diagnosis. Screening for PTSD in jails may help identify older inmates who would benefit from additional mental health treatment and reentry planning to improve health in this population. PMID- 27367337 TI - Reversible hippocampal lesions detected on magnetic resonance imaging in two cases of transient selective amnesia for simple machine operation. AB - We report two extremely rare cases involving the development of transient selective retrograde amnesia for simple machine operation lasting for several hours. A 61-year-old male taxi driver suddenly became unable to operate a taximeter, and a 66-year-old female janitor suddenly became unable to use a fax machine. They could precisely recount their episodes to others both during and after the attacks, and their memories during their attacks corresponded to the memory of the witness and the medical records of the doctor, respectively. Therefore, it appears that these individuals remained alert and did not develop anterograde amnesia during their attacks. On day 4, they underwent high resolution magnetic resonance imaging (MRI), and diffusion-weighted MRI with 2-mm section thickness revealed small high-intensity signal lesions in the left hippocampal cornu ammonis area 1 (CA1) region. However, these lesions disappeared during the chronic phase. This is the first report describing lesions detected by MRI in patients with transient selective amnesia without anterograde amnesia. Reversible damage to the hippocampal CA1 region may cause transient selective amnesia by impairing the retrieval of relevant memories. PMID- 27367336 TI - Novel C-Ring-Hydroxy-Substituted Controlled Deactivation Cannabinergic Analogues. AB - In pursuit of safer controlled-deactivation cannabinoids with high potency and short duration of action, we report the design, synthesis, and pharmacological evaluation of novel C9- and C11-hydroxy-substituted hexahydrocannabinol (HHC) and tetrahydrocannabinol (THC) analogues in which a seven atom long side chain, with or without 1'-substituents, carries a metabolically labile 2',3'-ester group. Importantly, in vivo studies validated our controlled deactivation approach in rodents and non-human primates. The lead molecule identified here, namely, butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a hexahydro-6H-benzo[c]chromen-3-yl]-2-methylpropanoate (AM7499), was found to exhibit remarkably high in vitro and in vivo potency with shorter duration of action than the currently existing classical cannabinoid agonists. PMID- 27367338 TI - Exploring the role of water in molecular recognition: predicting protein ligandability using a combinatorial search of surface hydration sites. AB - The interaction between any two biological molecules must compete with their interaction with water molecules. This makes water the most important molecule in medicine, as it controls the interactions of every therapeutic with its target. A small molecule binding to a protein is able to recognize a unique binding site on a protein by displacing bound water molecules from specific hydration sites. Quantifying the interactions of these water molecules allows us to estimate the potential of the protein to bind a small molecule. This is referred to as ligandability. In the study, we describe a method to predict ligandability by performing a search of all possible combinations of hydration sites on protein surfaces. We predict ligandability as the summed binding free energy for each of the constituent hydration sites, computed using inhomogeneous fluid solvation theory. We compared the predicted ligandability with the maximum observed binding affinity for 20 proteins in the human bromodomain family. Based on this comparison, it was determined that effective inhibitors have been developed for the majority of bromodomains, in the range from 10 to 100 nM. However, we predict that more potent inhibitors can be developed for the bromodomains BPTF and BRD7 with relative ease, but that further efforts to develop inhibitors for ATAD2 will be extremely challenging. We have also made predictions for the 14 bromodomains with no reported small molecule K d values by isothermal titration calorimetry. The calculations predict that PBRM1(1) will be a challenging target, while others such as TAF1L(2), PBRM1(4) and TAF1(2), should be highly ligandable. As an outcome of this work, we assembled a database of experimental maximal K d that can serve as a community resource assisting medicinal chemistry efforts focused on BRDs. Effective prediction of ligandability would be a very useful tool in the drug discovery process. PMID- 27367339 TI - [Septoplasty and tonsillectomy: acute stress response as a measure of effectiveness of local anesthetics]. AB - AIM: To compare the effectiveness of lidocaine and articaineused as local anesthetics in septoplasty and tonsillectomy based on the physiological stress response. PATIENTS AND METHODS: The study included 125 patients with nasal septum deviation (NSD) and chronic tonsillitis (CT). The patients presenting with NSD were divided into two groups. Those comprising group 1A (n=32) were treated with a 2% lidocaine solution for local infiltration analgesia (LIA), the patients of group 1B (n=30) were given 2%articaine as LIA. Group 2A contained 32 patients with CT treated with lidocaine, group 2B consisted of 31 patients given articaine. In all the patients, the overall heart rate variability (HRV) including its high, low, and very low components was measured. RESULTS: Evaluation of HRV revealed a certain degree of disadaptation in the patients of groups 1B and 2A. High dispersion of SDANN, SDNN index, andrMSSD in group 1Bas well as SDANN values in group 2A indicates the sympathetic/parasympathetic imbalance. The high-frequency component was augmented in group 2B which suggested the prevalence of parasympathetic tone, but its high dispersion was just aswell indicative of disadaptation. CONCLUSION: Local analgesia with articaine during septoplasty leads tosympathetic/parasympathetic imbalance during the early postoperative period. Lidocaine analgesia for tonsillectomy does not prevent disadaptation induced by surgical stress. PMID- 27367340 TI - [The specific features of the vestibular function in the patients presenting with sensorineural hearing loss of vascular genesis]. AB - The authors consider the specific features of the vestibular function in the patients with sensorineural hearing loss of vascular genesis. The study included 60 patients at the age from 28 to 75 years presenting with sensorineural impairment of hearing of vascular genesis. All of them were examined with the use of the extended otoneurological method. The data obtained were compared with the structural changes and hemodynamic characteristics of vertebral arteries (VA) and internal carotid arteries (ICA) and with the results of magnetic resonance imaging (MRI) of the brain. PMID- 27367341 TI - [The use of the Surgitron radiowave scalpel for the surgical treatment of external ear neoplasms]. AB - The objective of the present study was to elucidate etiology and clinical picture of the tumours of the external ear as well as to evaluate the effectiveness of their radiowave surgery. We sought to optimize the surgical strategy for the treatment of tumour-like masses, benign and malignant neoplasms of the external ear with the use of the Surgitron radiowave scalpel. PMID- 27367342 TI - [The application of the lyophilized xenodermoimplants for the plastic correction of the external auditory canal and nasal septum perforation]. AB - The objective of the present work was to improve the effectiveness of the treatment of atresia of the external auditory canal (EAC). Atresia of external acoustic meatus is a result of a mechanical or thermal injury but can also develop after a surgical intervention for the removal of foreign bodies, benign and malignant tumours. This condition is frequently associated with the narrowing and obliteration of EAC leading to the marked impairment of hearing despite preservation of the middle ear structures. Plastic correction of the external auditory canal for the purpose of its broadening does not always produce the desired result. To improve the efficiency of such intervention, we made use of the lyophilized xenodermoimplants based on porcine skin. Such preparation were applied in 19 patients; patency of the external auditory canal was restored in 16 cases. PMID- 27367343 TI - [Analysis of the results of a questionnaire survey among the patients presenting with nasal cavity and paranasal sinuses diseases concerning organization and quality of specialized medical assistance]. AB - The objective of the present study was to evaluate the influence of the medico social factors on the development of nasal cavity and paranasal sinuses diseases and satisfaction of the patients with the quality of the provided specialized medical assistance. The approaches to the treatment of such patient at the pre hospital and hospital levels are discussed. PMID- 27367344 TI - [Etiology and pathogenesis of glomus tumours (chemodectomas) of the base of the skull]. AB - The objective of the present work was to describe the poorly known history of the development of the nomenclature of glomus tumours (chemodectomas) of the base of the skull, elucidate etiology and pathogenesis of these neoplasms. The authors present a chronological table illustrating the progress of etiological and pathogenetic studies as well as the surgical treatment of the tumours. The results of analysis and discussion of the controversial issues of the nomenclature are reported. PMID- 27367345 TI - [Multiple primary metachronous cancer of the ear (a case report)]. PMID- 27367346 TI - [The unusual localization of an oesophageal foreign body]. PMID- 27367347 TI - [The use of thresholds of electrically evoked short-latent auditory potentials for the adjustment of the speech processors in the patients undergoing cochlear implantation]. AB - The objective of the present study was to determine the thresholds of electrically evoked short-latent auditory potentials by the mathematical method and to elucidate the relationship between these parameters and the subjective maximally comfortable levels in the patients undergoing cochlear implantation. The electrically evoked short-latent auditory potentials were recorded in two groups of patients with different stimulation frequency (17 and 43 Hz). The use of the mathematical method of linear regression of the amplitude (peak V) growth function for determining the thresholds of electrically evoked short-latent auditory potentials has a number of advantages over visual detection of the threshold level. To increase the reliability of the data obtained, low stimulation frequencies need to be used when recording electrically evoked short latent auditory potentials (17 Hz). The calculated thresholds of electrically evoked short-latent auditory potentials can be used to estimate the subjective maximally comfortable levels for the adjustment of the speech processors when it is impossible to register electrically induced stapedial reflexes and electrically induced total action potentials of the auditory nerve in the patients having cochlear implants. PMID- 27367348 TI - [Comparative analysis of the effectiveness of bypass surgery and laser myringotomy used to treat exudative otitis medium]. AB - The objective of the present study was the comparative analysis of the surgical method employed for the treatment of exudative otitis medium, such as bypass surgery and laser myringotomy. The study included 125 patients suffering from the said pathology. The following two methods were used in cases of poor efficiency of conservative therapy: laser myringotomy with the use of a LUMENISc CO2-laser operated at a wavelength of 10.6 mcm with the SurgiTouch scanner and bypass of the tympanic cavity. Each of these methods was applied to treat 38 patients. It was shown that discharge from the treated tympanic cavity stopped sooner after laser myringotomy than after surgical bypass. The recovery of hearing ability according to the results of tonal threshold audiometry also took less time after laser myringotomy than after surgical bypass. The same is true with respect to the restoration of the drainage function of the Eustachian tubes. The frequency of recurrent exudate formation (in percent) in the patients undergoing laser myringotomy was significantly lower than after surgical bypass. PMID- 27367349 TI - [The algorithm for rehabilitation of the patients presenting with laryngeal cancer following open functionally sparing operations]. AB - The objective of the present study was to increase the efficiency of the treatment of the patients presenting with laryngeal cancer by the enhancement of the functional reserve of the preserved portion of the larynx and the prevention of the narrowing of its lumen. Another objective was to develop an algorithm for the rehabilitation of the patients with laryngeal localization of the tumour following open functionally sparing operations that consists of the operative and postoperative stages. During the period from 2006 to 2014, a total of 71 patients underwent functionally sparing operations. 66 of them were operated for laryngeal cancer, 1 for thyroid cancer spreading over trachea and larynx, 3 for papillomatosis. Resection of the larynx in the vertical and horizontal planes was performed in 62 and 9 patients respectively. Vertical plane surgery included the following procedures: fronto-lateral resection of the larynx in 51 patients, extended fronto-lateral resection in 10, and combined resection in 1 patient. It is concluded that the systemic approach to the treatment of the patients with laryngeal cancer and the proposed algorithm for their rehabilitation made it possible to restore the laryngeal function in 68 of the 71 patients (95.8%). PMID- 27367350 TI - [The influence of accessory ostia on the development and the course of the inflammatory processes in the maxillary sinuses]. AB - The objective of the present study was to detect accessory ostia in the patients presenting with various diseases of the maxillary sinuses. We undertook the endoscopic examination of the middle meatuses in 250 patients. It was shown that accessory ostia can be especially frequently seen in the patients with chronic maxillary sinusitis and nasal septum deviation. PMID- 27367351 TI - [The current views of the treatment of diffuse external otitis]. AB - The objective of the present study was to evaluate the clinical effectiveness and safety of the local application of triderm for the treatment of diffuse external otitis. The study included 68 patients presenting with bacterial and fungal diffuse external otitis. The treatment in the form of local empiric therapy was continued till the results of microbiological treatment became apparent. The beneficial outcome achieved in 91.2% of the patients was clinically manifest as the regression of the inflammatory process in the external auditory meatus. No complications, such as ototoxic events, either local or systemic allergic reactions, were documented. The authors substantiate the possibility of the application of the medication under consideration for the treatment of diffuse external otitis based on the knowledge of the mechanism of the actin of its constituent components, viz. betamethasone, dipropionate, gentamicin sulfate, and clotrimazole, taking into account the occurrence of the most common causative agents of diffuse external otitis. It is concluded that triderm is a safe medication for the local application and, probably, for the initial empiric therapy of diffuse external otitis to be continued till the results of the microbiological treatment become apparent. PMID- 27367352 TI - [The non-damaging method for the insertion of a standard electrode for cochlear ossification]. AB - The objective of the present study was to develop the non-damaging method for the insertion of a standard electrode for cochlear ossification with a view to improving the results of hearing and speech rehabilitation of the patients presenting with grade IV sensorineural impairment of hearing. Twenty preparations of the cadaveric temporal bone were used to investigate topographic and anatomical relationships in the main structures of the middle and internal ears, viz. the second cochlear coil, vestibulum and its windows, processus cochleaformis, spiral lamina, and modiolus. The optimal method for the insertion of a standard electrode into the spiral canal of the cochlea after the removal of the ossified structures is proposed. The optimal site for constructing the second colostomy is determined that allows the spiral plate and modiolus to be maximally preserved. The proposed method was employed to treat 11 patients with grade IV sensorineural impairment of hearing and more than 5 mm ossification of the basal cochlear coil. With this method, it proved possible to insert the maximum number of electrodes into the cochlear spiral canal and thereby to obtain excellent results of hearing and speech rehabilitation in the patients with the ossified cochlea. PMID- 27367353 TI - [A coughing patients makes a visit to the otorhinolaryngologist's office: the practical aspects of diagnostics and treatment]. AB - This article summarizes the modern concepts of the most common causes and mechanism underlying the development of cough. The significance of pathogenetic cough-suppressant therapy is emphasized with special reference to the following aspects: the importance of reducing the thickness or bronchial secretions, its more efficient removal from the lumen of the respiratory passages, creation of the prerequisites for regression of the inflammatory process, lowering the intensity of cough, improvement of subjective feelings and the quality of life of a given patient. The advantages of the application of the compounded preparations containing synergic components responsible for the high therapeutic effectiveness of these medicines is demonstrated as exemplified by the ingredients of the ascoril expectorant. It is concluded that this medication should be recommended for the treatment of patients suffering from cough of the known nature. PMID- 27367354 TI - [Foreign bodies in the external auditory canal and tympanic cavity]. AB - The rare clinical case of a patient with chronic otitis media and foreign body in the middle ear - a micro earphone in the tympanic cavity - is described in this article. The diagnostics, possible complications, and surgical treatment are discussed. PMID- 27367355 TI - [The long-term presence of a foreign body in the oesophagus]. PMID- 27367356 TI - [The clinical manifestation of the neurovascular conflict of the vestibulocochlear nerve]. PMID- 27367357 TI - Complex Spine Pathology Simulator: An Innovative Tool for Advanced Spine Surgery Training. AB - Background Technical advancements in spine surgery have made possible the treatment of increasingly complex pathologies with less morbidity. Time constraints in surgeons' training have made it necessary to develop new training models for spine pathology. Objective To describe the application of a novel compound, Stratathane resin ST-504 derived polymer (SRSDP), that can be injected at different spinal target locations to mimic spinal epidural, subdural extra axial, and intra-axial pathologies for the use in advanced surgical training. Material and Methods Fresh-frozen thoracolumbar and cervical spine segments of human and sheep cadavers were used to study the model. SRSDP is initially liquid after mixing, allowing it to be injected into target areas where it expands and solidifies, mimicking the entire spectrum of spinal pathologies. Results Different polymer concentrations have been codified to vary adhesiveness, texture, spread capability, deformability, and radiologic visibility. Polymer injection was performed under fluoroscopic guidance through pathology-specific injection sites that avoided compromising the surgical approach for subsequent excision of the artificial lesion. Inflation of a balloon catheter of the desired size was used to displace stiff cadaveric neurovascular structures to mimic pathology-related mass effect. Conclusion The traditional cadaveric training models principally only allow surgeons to practice the surgical approach. The complex spine pathology simulator is a novel educational tool that in a user friendly, low-cost fashion allows trainees to practice advanced technical skills in the removal of complex spine pathology, potentially shortening some of the aspects of the learning curve of operative skills that may otherwise take many years to acquire. PMID- 27367358 TI - Early Experience with Combining Awake Craniotomy and Intraoperative Navigable Ultrasound for Resection of Eloquent Region Gliomas. AB - Introduction Optimal resection of tumors in eloquent locations requires a combination of intraoperative imaging and functional monitoring during surgery. Combining awake surgery with intraoperative magnetic resonanceis logistically challenging. Navigable ultrasound (US) is a useful alternative in such cases. Methods A total of 22 subjects with eloquent tumors were operated on (1 intended biopsy and 21 intended radical resections) using combined modality three dimensional (3D) US and awake craniotomy with intraoperative clinical monitoring. We describe the technical details for these cases specifically addressing the feasibility of combining the two modalities. Results US was used for resection control in 18 cases. There were technical limitations in three cases. Transient intraoperative worsening was encountered in eight, necessitating premature termination of the procedure. All patients tolerated the awake procedure well. Mean duration of the surgery was 3.2 hours. Radical resections were obtained in 14 of 18 where this was intended and in 12 of the 13 where there was no adverse intraoperative monitoring event prompting premature termination of the resection. Conclusions Combining awake surgery with 3DUS is feasible and beneficial. It does not entail any additional surgical workflow modification or patient discomfort. This combined modality intraoperative monitoring can be beneficial for eloquent region tumors. PMID- 27367359 TI - Direct Carotid Exposure for Neuroendovascular Approaches. AB - Objective The transfemoral approach is a common route for catheterization of the supra-aortic vessels in neuroendovascular therapy. However, in some cases, the patient's anatomy prevents transfemoral catheterization or distal access to the carotid s. In such cases, direct carotid exposure (DCE) for neuroendovascular approaches may be used to treat cerebrovascular diseases. Methods We present 11 cases in which we were unable to perform the distal approach and DCE was the preferred neuroendovascular treatment procedure. Results DCE was performed on 11 patients with cerebral aneurysm (n = 8), carotid cavernous fistula (CCF) (n = 1), malignant brain tumor (n = 1), and carotid angioplasty and stenting (n = 1). Ten patients were female; one was male. Ages ranged from 63 to 87 years (mean: 71.36 years). Coil embolization was performed on patients with cerebral aneurysm and CCF. The patient with a malignant brain tumor underwent polyvinyl alcohol particle embolization. The only complication was a carotid artery dissection that occurred in one patient during stenting. Conclusion DCE for neuroendovascular approaches can be used as an alternative for patients with tortuous vasculature access in the femoral route. In such patients, a combination of neuroendovascular treatment and surgery in a hybrid operating room with angiography is preferred. PMID- 27367360 TI - Needle electromyography of the frontalis muscle in patients with amyotrophic lateral sclerosis. AB - INTRODUCTION: We sought to determine which muscles to choose for better assessment of the craniobulbar region in establishing the diagnosis of amyotrophic lateral sclerosis (ALS). METHODS: We studied the frontalis muscle in 83 controls and compared it with the tongue, sternocleidomastoid (SCM), and trapezius muscles in 105 definite or probable ALS patients (54 bulbar, 51 nonbulbar). RESULTS: More patients achieved complete relaxation of the frontalis muscle than the tongue or SCM. Motor unit potentials were of longer duration and higher amplitude in ALS patients than in controls (P < 0.05). The frontalis had the same frequency of spontaneous potentials as the tongue, SCM, and trapezius muscles in bulbar ALS patients, but fewer than in the trapezius in nonbulbar patients. CONCLUSIONS: Examining the frontalis provides useful information in establishing the diagnosis of ALS by identifying clinically evident or subclinical abnormalities in the craniobulbar region. Muscle Nerve 54: 1093-1096, 2016. PMID- 27367361 TI - In vitro and in vivo hemocompatibility evaluation of a new dermatan sulfate modified PET patch for vascular repair surgery. AB - The development of new vascular devices requires to study the effects of materials on blood cells and on coagulation, both in vitro and in vivo. In this study, we have developed a new material by grafting dermatan sulfate (DS) from shark skin onto polyethylene terephthalate (PET). We have evaluated the haemocompatibility of PET-DS material in vitro by measuring thrombin generation, plasma recalcification time, hemolytic activity, and platelet adhesion and in vivo with a model of vascular patch in rat abdominal aorta. In vitro, our results have shown that PET-DS is a nonhemolytic material, able to inhibit thrombin generation and platelet adhesion. In vivo studies by Doppler echographic evaluation 20 days after implantation have shown that the PET-DS patch was integrated in the vessel wall and covered by a layer of cells. In conclusion, PET DS has good haemocompatibility properties and could be a promising tool for vascular surgery. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2001-2009, 2017. PMID- 27367362 TI - Effectiveness of endoscopic gastric cancer screening in a rural area of Linzhou, China: results from a case-control study. AB - In China, a large burden of gastric cancer has remained, and endoscopic screening was expected to reduce gastric cancer mortality. Therefore, a population-based case-control study was conducted to evaluate the screening effect. The gastric cancer screening program was initiated in Linzhou in the year 2005, and endoscopic examination with indicative biopsy, for residents aged 40-69 years, was used to detect early cancer and precancerous lesion. In this study, cases were defined as individuals who had died of gastric cancer, which were selected from Linzhou Cancer Registry database. Controls were residents (six per case), who had not died of gastric cancer, from the same area as the case, and matched by gender and age (+/-2 years). The exposure status, whether cases and controls ever attended the screening or not, was acquired by inspecting the well documented screening records. Conditional logistic regression model was used to estimate the odds ratios (OR) and their 95% confidence intervals (95% CI). A total of 313 cases and 1876 controls were included in our analysis. Compared with subjects who never participated in screening, the overall OR for individuals who ever participated in screening was 0.72(95% CI: 0.54-0.97). The OR for lag time 4 years or longer was 0.68(95% CI: 0.47-0.98) and the OR for those who were aged 50 59 years were 0.56 (0.37-0.85). The results suggest a 28% reduction in risk of gastric cancer mortality by endoscopic screening, which may have significant implications for gastric cancer screening in rural areas of China. PMID- 27367363 TI - DAPPLE 2: a Tool for the Homology-Based Prediction of Post-Translational Modification Sites. AB - The post-translational modification of proteins is critical for regulating their function. Although many post-translational modification sites have been experimentally determined, particularly in certain model organisms, experimental knowledge of these sites is severely lacking for many species. Thus, it is important to be able to predict sites of post-translational modification in such species. Previously, we described DAPPLE, a tool that facilitates the homology based prediction of one particular post-translational modification, phosphorylation, in an organism of interest using known phosphorylation sites from other organisms. Here, we describe DAPPLE 2, which expands and improves upon DAPPLE in three major ways. First, it predicts sites for many post-translational modifications (20 different types) using data from several sources (15 online databases). Second, it has the ability to make predictions approximately 2-7 times faster than DAPPLE depending on the database size and the organism of interest. Third, it simplifies and accelerates the process of selecting predicted sites of interest by categorizing them based on gene ontology terms, keywords, and signaling pathways. We show that DAPPLE 2 can successfully predict known human post-translational modification sites using, as input, known sites from species that are either closely (e.g., mouse) or distantly (e.g., yeast) related to humans. DAPPLE 2 can be accessed at http://saphire.usask.ca/saphire/dapple2 . PMID- 27367364 TI - Brain activation in response to bladder filling in healthy adults: An activation likelihood estimation meta-analysis of neuroimaging studies. AB - AIMS: Recent studies have used different neuroimaging techniques and identified various brain regions that are activated during bladder filling. However, there is a lack of consensus regarding which of these brain regions regulate the process of urine storage. The aim of this meta-analysis is to identify brain regions that are commonly activated during bladder filling in healthy adults across different studies. METHODS: PubMed was searched for neuroimaging studies investigating the effects of bladder filling on regional brain activation. Studies were excluded if they did not report brain activation differences from whole-brain group analysis by comparing the state of bladder filling with the state of bladder rest. The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. RESULTS: We identified 14 neuroimaging studies examining brain activation in response to experimental bladder filling in 181 healthy subjects, which reported 89 foci for ALE analysis. The meta-analysis revealed significant activation in multiple brain regions including thalamus (bilaterally), right insula, cerebellum, and brainstem (bilaterally). CONCLUSIONS: Several key brain regions involved in sensory processing are commonly activated during bladder filling in healthy adults across different studies. Neurourol. Urodynam. 36:960-965, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27367365 TI - Natural Framework for Device-Independent Quantification of Quantum Steerability, Measurement Incompatibility, and Self-Testing. AB - We introduce the concept of assemblage moment matrices, i.e., a collection of matrices of expectation values, each associated with a conditional quantum state obtained in a steering experiment. We demonstrate how it can be used for quantum states and measurements characterization in a device-independent manner, i.e., without invoking any assumption about the measurement or the preparation device. Specifically, we show how the method can be used to lower bound the steerability of an underlying quantum state directly from the observed correlation between measurement outcomes. Combining such device-independent quantifications with earlier results established by Piani and Watrous [Phys. Rev. Lett. 114, 060404 (2015)], our approach immediately provides a device-independent lower bound on the generalized robustness of entanglement, as well as the usefulness of the underlying quantum state for a type of subchannel discrimination problem. In addition, by proving a quantitative relationship between steering robustness and the recently introduced incompatibility robustness, our approach also allows for a device-independent quantification of the incompatibility between various measurements performed in a Bell-type experiment. Explicit examples where such bounds provide a kind of self-testing of the performed measurements are provided. PMID- 27367366 TI - Hubbard Model for Atomic Impurities Bound by the Vortex Lattice of a Rotating Bose-Einstein Condensate. AB - We investigate cold bosonic impurity atoms trapped in a vortex lattice formed by condensed bosons of another species. We describe the dynamics of the impurities by a bosonic Hubbard model containing occupation-dependent parameters to capture the effects of strong impurity-impurity interactions. These include both a repulsive direct interaction and an attractive effective interaction mediated by the Bose-Einstein condensate. The occupation dependence of these two competing interactions drastically affects the Hubbard model phase diagram, including causing the disappearance of some Mott lobes. PMID- 27367367 TI - Energy Exchange in Driven Open Quantum Systems at Strong Coupling. AB - The time-dependent energy transfer in a driven quantum system strongly coupled to a heat bath is studied within an influence functional approach. Exact formal expressions for the statistics of energy dissipation into the different channels are derived. The general method is applied to the driven dissipative two-state system. It is shown that the energy flows obey a balance relation, and that, for strong coupling, the interaction may constitute the major dissipative channel. Results in analytic form are presented for the particular value K=1/2 of strong Ohmic dissipation. The energy flows show interesting behaviors including driving induced coherences and quantum stochastic resonances. It is found that the general characteristics persists for K near 1/2. PMID- 27367368 TI - Towards a Theory of Metastability in Open Quantum Dynamics. AB - By generalizing concepts from classical stochastic dynamics, we establish the basis for a theory of metastability in Markovian open quantum systems. Partial relaxation into long-lived metastable states-distinct from the asymptotic stationary state-is a manifestation of a separation of time scales due to a splitting in the spectrum of the generator of the dynamics. We show here how to exploit this spectral structure to obtain a low dimensional approximation to the dynamics in terms of motion in a manifold of metastable states constructed from the low-lying eigenmatrices of the generator. We argue that the metastable manifold is in general composed of disjoint states, noiseless subsystems, and decoherence-free subspaces. PMID- 27367369 TI - Entanglement and Coherence in Quantum State Merging. AB - Understanding the resource consumption in distributed scenarios is one of the main goals of quantum information theory. A prominent example for such a scenario is the task of quantum state merging, where two parties aim to merge their tripartite quantum state parts. In standard quantum state merging, entanglement is considered to be an expensive resource, while local quantum operations can be performed at no additional cost. However, recent developments show that some local operations could be more expensive than others: it is reasonable to distinguish between local incoherent operations and local operations which can create coherence. This idea leads us to the task of incoherent quantum state merging, where one of the parties has free access to local incoherent operations only. In this case the resources of the process are quantified by pairs of entanglement and coherence. Here, we develop tools for studying this process and apply them to several relevant scenarios. While quantum state merging can lead to a gain of entanglement, our results imply that no merging procedure can gain entanglement and coherence at the same time. We also provide a general lower bound on the entanglement-coherence sum and show that the bound is tight for all pure states. Our results also lead to an incoherent version of Schumacher compression: in this case the compression rate is equal to the von Neumann entropy of the diagonal elements of the corresponding quantum state. PMID- 27367370 TI - Entropic Nonsignaling Correlations. AB - We introduce the concept of entropic nonsignaling correlations, i.e., entropies arising from probabilistic theories that are compatible with the fact that we cannot transmit information instantaneously. We characterize and show the relevance of these entropic correlations in a variety of different scenarios, ranging from typical Bell experiments to more refined descriptions such as bilocality and information causality. In particular, we apply the framework to derive the first entropic inequality testing genuine tripartite nonlocality in quantum systems of arbitrary dimension and also prove the first known monogamy relation for entropic Bell inequalities. Further, within the context of complex Bell networks, we show that entropic nonlocal correlations can be activated. PMID- 27367371 TI - Observation of Quantum Fingerprinting Beating the Classical Limit. AB - Quantum communication has historically been at the forefront of advancements, from fundamental tests of quantum physics to utilizing the quantum-mechanical properties of physical systems for practical applications. In the field of communication complexity, quantum communication allows the advantage of an exponential reduction in the transmitted information over classical communication to accomplish distributed computational tasks. However, to date, demonstrating this advantage in a practical setting continues to be a central challenge. Here, we report a proof-of-principle experimental demonstration of a quantum fingerprinting protocol that for the first time surpasses the ultimate classical limit to transmitted information. Ultralow noise superconducting single-photon detectors and a stable fiber-based Sagnac interferometer are used to implement a quantum fingerprinting system that is capable of transmitting less information than the classical proven lower bound over 20 km standard telecom fiber for input sizes of up to 2 Gbits. The results pave the way for experimentally exploring the advanced features of quantum communication and open a new window of opportunity for research in communication complexity and testing the foundations of physics. PMID- 27367372 TI - Stabilizing Entanglement via Symmetry-Selective Bath Engineering in Superconducting Qubits. AB - Bath engineering, which utilizes coupling to lossy modes in a quantum system to generate nontrivial steady states, is a tantalizing alternative to gate- and measurement-based quantum science. Here, we demonstrate dissipative stabilization of entanglement between two superconducting transmon qubits in a symmetry selective manner. We utilize the engineered symmetries of the dissipative environment to stabilize a target Bell state; we further demonstrate suppression of the Bell state of opposite symmetry due to parity selection rules. This implementation is resource efficient, achieves a steady-state fidelity F=0.70, and is scalable to multiple qubits. PMID- 27367373 TI - Self-Organized Bistability Associated with First-Order Phase Transitions. AB - Self-organized criticality elucidates the conditions under which physical and biological systems tune themselves to the edge of a second-order phase transition, with scale invariance. Motivated by the empirical observation of bimodal distributions of activity in neuroscience and other fields, we propose and analyze a theory for the self-organization to the point of phase coexistence in systems exhibiting a first-order phase transition. It explains the emergence of regular avalanches with attributes of scale invariance that coexist with huge anomalous ones, with realizations in many fields. PMID- 27367374 TI - Nonequilibrium Tuning of the Thermal Casimir Effect. AB - In net-neutral systems correlations between charge fluctuations generate strong attractive thermal Casimir forces and engineering these forces to optimize nanodevice performance is an important challenge. We show how the normal and lateral thermal Casimir forces between two plates containing Brownian charges can be modulated by decorrelating the system through the application of an electric field, which generates a nonequilibrium steady state with a constant current in one or both plates, reducing the ensuing fluctuation-generated normal force while at the same time generating a lateral drag force. This hypothesis is confirmed by detailed numerical simulations as well as an analytical approach based on stochastic density functional theory. PMID- 27367375 TI - Le Chatelier Principle for Out-of-Equilibrium and Boundary-Driven Systems: Application to Dynamical Phase Transitions. AB - A stability analysis is presented for boundary-driven and out-of-equilibrium systems in the framework of the hydrodynamic macroscopic fluctuation theory. A Hamiltonian description is proposed which allows us to thermodynamically interpret the additivity principle. A necessary and sufficient condition for the validity of the additivity principle is obtained as an extension of the Le Chatelier principle. These stability conditions result from a diagonal quadratic form obtained using the cumulant generating function. This approach allows us to provide a proof for the stability of the weakly asymmetric exclusion process and to reduce the search for stability to the solution of two coupled linear ordinary differential equations instead of nonlinear partial differential equations. Additional potential applications of these results are discussed in the realm of classical and quantum systems. PMID- 27367376 TI - Ultrasensitive Magnetometer using a Single Atom. AB - Precision sensing, and in particular high precision magnetometry, is a central goal of research into quantum technologies. For magnetometers, often trade-offs exist between sensitivity, spatial resolution, and frequency range. The precision, and thus the sensitivity of magnetometry, scales as 1/sqrt[T_{2}] with the phase coherence time T_{2} of the sensing system playing the role of a key determinant. Adapting a dynamical decoupling scheme that allows for extending T_{2} by orders of magnitude and merging it with a magnetic sensing protocol, we achieve a measurement sensitivity even for high frequency fields close to the standard quantum limit. Using a single atomic ion as a sensor, we experimentally attain a sensitivity of 4.6 pT/sqrt[Hz] for an alternating-current magnetic field near 14 MHz. Based on the principle demonstrated here, this unprecedented sensitivity combined with spatial resolution in the nanometer range and tunability from direct current to the gigahertz range could be used for magnetic imaging in as of yet inaccessible parameter regimes. PMID- 27367380 TI - Theory-Agnostic Constraints on Black-Hole Dipole Radiation with Multiband Gravitational-Wave Astrophysics. AB - The aLIGO detection of the black-hole binary GW150914 opens a new era for probing extreme gravity. Many gravity theories predict the emission of dipole gravitational radiation by binaries. This is excluded to high accuracy in binary pulsars, but entire classes of theories predict this effect predominantly (or only) in binaries involving black holes. Joint observations of GW150914-like systems by aLIGO and eLISA will improve bounds on dipole emission from black-hole binaries by 6 orders of magnitude relative to current constraints, provided that eLISA is not dramatically descoped. PMID- 27367381 TI - Time Dependence of the Electron and Positron Components of the Cosmic Radiation Measured by the PAMELA Experiment between July 2006 and December 2015. AB - Cosmic-ray electrons and positrons are a unique probe of the propagation of cosmic rays as well as of the nature and distribution of particle sources in our Galaxy. Recent measurements of these particles are challenging our basic understanding of the mechanisms of production, acceleration, and propagation of cosmic rays. Particularly striking are the differences between the low energy results collected by the space-borne PAMELA and AMS-02 experiments and older measurements pointing to sign-charge dependence of the solar modulation of cosmic ray spectra. The PAMELA experiment has been measuring the time variation of the positron and electron intensity at Earth from July 2006 to December 2015 covering the period for the minimum of solar cycle 23 (2006-2009) until the middle of the maximum of solar cycle 24, through the polarity reversal of the heliospheric magnetic field which took place between 2013 and 2014. The positron to electron ratio measured in this time period clearly shows a sign-charge dependence of the solar modulation introduced by particle drifts. These results provide the first clear and continuous observation of how drift effects on solar modulation have unfolded with time from solar minimum to solar maximum and their dependence on the particle rigidity and the cyclic polarity of the solar magnetic field. PMID- 27367377 TI - Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy. AB - We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8+/ 0.7(stat)+/-6.7(syst) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first principles calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory. PMID- 27367384 TI - Higgs Transverse-Momentum Resummation in Direct Space. AB - We propose a new approach to the resummation of the transverse-momentum distribution of a high-mass color-singlet system in hadronic collisions. The resummation is performed in momentum space and is free of kinematic singularities at small transverse momentum. We derive a formula accurate at the next-to-next-to leading-logarithmic level, and present the first matched predictions to next-to next-to-leading order for Higgs-boson production in gluon fusion at the LHC. This method can be adapted to all observables featuring kinematic cancellations in the infrared region. PMID- 27367387 TI - Resonant Rydberg Dressing of Alkaline-Earth Atoms via Electromagnetically Induced Transparency. AB - We develop an approach to generate finite-range atomic interactions via optical Rydberg-state excitation and study the underlying excitation dynamics in theory and experiment. In contrast to previous work, the proposed scheme is based on resonant optical driving and the establishment of a dark state under conditions of electromagnetically induced transparency (EIT). Analyzing the driven dissipative dynamics of the atomic gas, we show that the interplay between coherent light coupling, radiative decay, and strong Rydberg-Rydberg atom interactions leads to the emergence of sizable effective interactions while providing remarkably long coherence times. The latter are studied experimentally in a cold gas of strontium atoms for which the proposed scheme is most efficient. Our measured atom loss is in agreement with the theoretical prediction based on binary effective interactions between the driven atoms. PMID- 27367385 TI - Precision Measurement of the Radiative beta Decay of the Free Neutron. AB - The standard model predicts that, in addition to a proton, an electron, and an antineutrino, a continuous spectrum of photons is emitted in the beta decay of the free neutron. We report on the RDK II experiment which measured the photon spectrum using two different detector arrays. An annular array of bismuth germanium oxide scintillators detected photons from 14 to 782 keV. The spectral shape was consistent with theory, and we determined a branching ratio of 0.00335+/-0.00005[stat]+/-0.00015[syst]. A second detector array of large area avalanche photodiodes directly detected photons from 0.4 to 14 keV. For this array, the spectral shape was consistent with theory, and the branching ratio was determined to be 0.00582+/-0.00023[stat]+/-0.00062[syst]. We report the first precision test of the shape of the photon energy spectrum from neutron radiative decay and a substantially improved determination of the branching ratio over a broad range of photon energies. PMID- 27367388 TI - Direct Measurement of Photon Recoil from a Levitated Nanoparticle. AB - The momentum transfer between a photon and an object defines a fundamental limit for the precision with which the object can be measured. If the object oscillates at a frequency Omega_{0}, this measurement backaction adds quanta hOmega_{0} to the oscillator's energy at a rate Gamma_{recoil}, a process called photon recoil heating, and sets bounds to coherence times in cavity optomechanical systems. Here, we use an optically levitated nanoparticle in ultrahigh vacuum to directly measure Gamma_{recoil}. By means of a phase-sensitive feedback scheme, we cool the harmonic motion of the nanoparticle from ambient to microkelvin temperatures and measure its reheating rate under the influence of the radiation field. The recoil heating rate is measured for different particle sizes and for different excitation powers, without the need for cavity optics or cryogenic environments. The measurements are in quantitative agreement with theoretical predictions and provide valuable guidance for the realization of quantum ground-state cooling protocols and the measurement of ultrasmall forces. PMID- 27367386 TI - Experimental Neutron Capture Rate Constraint Far from Stability. AB - Nuclear reactions where an exotic nucleus captures a neutron are critical for a wide variety of applications, from energy production and national security, to astrophysical processes, and nucleosynthesis. Neutron capture rates are well constrained near stable isotopes where experimental data are available; however, moving far from the valley of stability, uncertainties grow by orders of magnitude. This is due to the complete lack of experimental constraints, as the direct measurement of a neutron-capture reaction on a short-lived nucleus is extremely challenging. Here, we report on the first experimental extraction of a neutron capture reaction rate on ^{69}Ni, a nucleus that is five neutrons away from the last stable isotope of Ni. The implications of this measurement on nucleosynthesis around mass 70 are discussed, and the impact of similar future measurements on the understanding of the origin of the heavy elements in the cosmos is presented. PMID- 27367389 TI - Experimental Measurement of the Second-Order Coherence of Supercontinuum. AB - We measure experimentally the second-order coherence properties of supercontinuum generated in a photonic crystal fiber. Our approach is based on measuring separately the quasicoherent and quasistationary contributions to the cross spectral density and mutual coherence functions using a combination of interferometric and nonlinear gating techniques. This allows us to introduce two dimensional coherence spectrograms which provide a direct characterization and convenient visualization of the spectrotemporal coherence properties. The measured second-order coherence functions are in very good agreement with numerical simulations based on the generalized nonlinear Schrodinger equation. Our results pave the way towards the full experimental characterization of supercontinuum coherence properties. More generally, they provide a generic approach for the complete experimental measurement of the coherence of broadband sources. PMID- 27367390 TI - Unidirectional Transition Waves in Bistable Lattices. AB - We present a model system for strongly nonlinear transition waves generated in a periodic lattice of bistable members connected by magnetic links. The asymmetry of the on-site energy wells created by the bistable members produces a mechanical diode that supports only unidirectional transition wave propagation with constant wave velocity. We theoretically justify the cause of the unidirectionality of the transition wave and confirm these predictions by experiments and simulations. We further identify how the wave velocity and profile are uniquely linked to the double-well energy landscape, which serves as a blueprint for transition wave control. PMID- 27367391 TI - Ensemble Space-Time Correlation of Plasma Turbulence in the Solar Wind. AB - Single point measurement turbulence cannot distinguish variations in space and time. We employ an ensemble of one- and two-point measurements in the solar wind to estimate the space-time correlation function in the comoving plasma frame. The method is illustrated using near Earth spacecraft observations, employing ACE, Geotail, IMP-8, and Wind data sets. New results include an evaluation of both correlation time and correlation length from a single method, and a new assessment of the accuracy of the familiar frozen-in flow approximation. This novel view of the space-time structure of turbulence may prove essential in exploratory space missions such as Solar Probe Plus and Solar Orbiter for which the frozen-in flow hypothesis may not be a useful approximation. PMID- 27367392 TI - Landau-Zener Bloch Oscillations with Perturbed Flat Bands. AB - Sinusoidal Bloch oscillations appear in band structures exposed to external fields. Landau-Zener (LZ) tunneling between different bands is usually a counteracting effect limiting Bloch oscillations. Here we consider a flat band network with two dispersive and one flat band, e.g., for ultracold atoms and optical waveguide networks. Using external synthetic gauge and gravitational fields we obtain a perturbed yet gapless band structure with almost flat parts. The resulting Bloch oscillations consist of two parts-a fast scan through the nonflat part of the dispersion structure, and an almost complete halt for substantial time when the atomic or photonic wave packet is trapped in the original flat band part of the unperturbed spectrum, made possible due to LZ tunneling. PMID- 27367393 TI - Statistical Nature of Atomic Disorder in Irradiated Crystals. AB - Atomic disorder in irradiated materials is investigated by means of x-ray diffraction, using cubic SiC single crystals as a model material. It is shown that, besides the determination of depth-resolved strain and damage profiles, x ray diffraction can be efficiently used to determine the probability density function (PDF) of the atomic displacements within the crystal. This task is achieved by analyzing the diffraction-order dependence of the damage profiles. We thereby demonstrate that atomic displacements undergo Levy flights, with a displacement PDF exhibiting heavy tails [with a tail index in the gamma=0.73-0.37 range, i.e., far from the commonly assumed Gaussian case (gamma=2)]. It is further demonstrated that these heavy tails are crucial to account for the amorphization kinetics in SiC. From the retrieved displacement PDFs we introduce a dimensionless parameter f_{D}^{XRD} to quantify the disordering. f_{D}^{XRD} is found to be consistent with both independent measurements using ion channeling and with molecular dynamics calculations. PMID- 27367395 TI - Absorbing State Phase Transition with Competing Quantum and Classical Fluctuations. AB - Stochastic processes with absorbing states feature examples of nonequilibrium universal phenomena. While the classical regime has been thoroughly investigated in the past, relatively little is known about the behavior of these nonequilibrium systems in the presence of quantum fluctuations. Here, we theoretically address such a scenario in an open quantum spin model which, in its classical limit, undergoes a directed percolation phase transition. By mapping the problem to a nonequilibrium field theory, we show that the introduction of quantum fluctuations stemming from coherent, rather than statistical, spin flips alters the nature of the transition such that it becomes first order. In the intermediate regime, where classical and quantum dynamics compete on equal terms, we highlight the presence of a bicritical point with universal features different from the directed percolation class in a low dimension. We finally propose how this physics could be explored within gases of interacting atoms excited to Rydberg states. PMID- 27367394 TI - Atomic-Scale Variations of the Mechanical Response of 2D Materials Detected by Noncontact Atomic Force Microscopy. AB - We show that noncontact atomic force microscopy (AFM) is sensitive to the local stiffness in the atomic-scale limit on weakly coupled 2D materials, as graphene on metals. Our large amplitude AFM topography and dissipation images under ultrahigh vacuum and low temperature resolve the atomic and moire patterns in graphene on Pt(111), despite its extremely low geometric corrugation. The imaging mechanisms are identified with a multiscale model based on density-functional theory calculations, where the energy cost of global and local deformations of graphene competes with short-range chemical and long-range van der Waals interactions. Atomic contrast is related with short-range tip-sample interactions, while the dissipation can be understood in terms of global deformations in the weakly coupled graphene layer. Remarkably, the observed moire modulation is linked with the subtle variations of the local interplanar graphene substrate interaction, opening a new route to explore the local mechanical properties of 2D materials at the atomic scale. PMID- 27367396 TI - Unscrambling Mixed Elements using High Angle Annular Dark Field Scanning Transmission Electron Microscopy. AB - The development of new nanocrystals with outstanding physicochemical properties requires a full three-dimensional (3D) characterization at the atomic scale. For homogeneous nanocrystals, counting the number of atoms in each atomic column from high angle annular dark field scanning transmission electron microscopy images has been shown to be a successful technique to get access to this 3D information. However, technologically important nanostructures often consist of more than one chemical element. In order to extend atom counting to heterogeneous materials, a new atomic lensing model is presented. This model takes dynamical electron diffraction into account and opens up new possibilities for unraveling the 3D composition at the atomic scale. Here, the method is applied to determine the 3D structure of Au@Ag core-shell nanorods, but it is applicable to a wide range of heterogeneous complex nanostructures. PMID- 27367397 TI - Intrinsic Charge Carrier Mobility in Single-Layer Black Phosphorus. AB - We present a theory for single- and two-phonon charge carrier scattering in anisotropic two-dimensional semiconductors applied to single-layer black phosphorus (BP). We show that in contrast to graphene, where two-phonon processes due to the scattering by flexural phonons dominate at any practically relevant temperatures and are independent of the carrier concentration n, two-phonon scattering in BP is less important and can be considered negligible at n?10^{13} cm^{-2}. At smaller n, however, phonons enter in the essentially anharmonic regime. Compared to the hole mobility, which does not exhibit strong anisotropy between the principal directions of BP (MU_{xx}/MU_{yy}~1.4 at n=10^{13} cm^{-2} and T=300 K), the electron mobility is found to be significantly more anisotropic (MU_{xx}/MU_{yy}~6.2). Absolute values of MU_{xx} do not exceed 250 (700) cm^{2} V^{-1} s^{-1} for holes (electrons), which can be considered as an upper limit for the mobility in BP at room temperature. PMID- 27367398 TI - Strong and Coherent Coupling between Localized and Propagating Phonon Polaritons. AB - Following the recent observation of localized phonon polaritons in user-defined silicon carbide nanoresonators, here we demonstrate strong and coherent coupling between those localized modes and propagating phonon polaritons bound to the surface of the nanoresonator's substrate. In order to obtain phase matching, the nanoresonators have been fabricated to serve the double function of hosting the localized modes, while also acting as a grating for the propagating ones. The coherent coupling between long lived, optically accessible localized modes, and low-loss propagative ones, opens the way to the design and realization of phonon polariton based coherent circuits. PMID- 27367399 TI - Bulk Fermi Surface of Charge-Neutral Excitations in SmB_{6} or Not: A Heat Transport Study. AB - Recently, there have been increasingly hot debates on whether a bulk Fermi surface of charge-neutral excitations exists in the topological Kondo insulator SmB_{6}. To unambiguously resolve this issue, we perform the low-temperature thermal conductivity measurements of a high-quality SmB_{6} single crystal down to 0.1 K and up to 14.5 T. Our experiments show that the residual linear term of thermal conductivity at the zero field is zero, within the experimental accuracy. Furthermore, the thermal conductivity is insensitive to the magnetic field up to 14.5 T. These results demonstrate the absence of fermionic charge-neutral excitations in bulk SmB_{6}, such as scalar Majorana fermions or spinons and, thus, exclude the existence of a bulk Fermi surface suggested by a recent quantum oscillation study of SmB_{6}. This puts a strong constraint on the explanation of the quantum oscillations observed in SmB_{6}. PMID- 27367400 TI - Charge-Insensitive Single-Atom Spin-Orbit Qubit in Silicon. AB - High fidelity entanglement of an on-chip array of spin qubits poses many challenges. Spin-orbit coupling (SOC) can ease some of these challenges by enabling long-ranged entanglement via electric dipole-dipole interactions, microwave photons, or phonons. However, SOC exposes conventional spin qubits to decoherence from electrical noise. Here, we propose an acceptor-based spin-orbit qubit in silicon offering long-range entanglement at a sweet spot where the qubit is protected from electrical noise. The qubit relies on quadrupolar SOC with the interface and gate potentials. As required for surface codes, 10^{5} electrically mediated single-qubit and 10^{4} dipole-dipole mediated two-qubit gates are possible in the predicted spin lifetime. Moreover, circuit quantum electrodynamics with single spins is feasible, including dispersive readout, cavity-mediated entanglement, and spin-photon entanglement. An industrially relevant silicon-based platform is employed. PMID- 27367401 TI - Orbital Selective Spin Excitations and their Impact on Superconductivity of LiFe_{1-x}Co_{x}As. AB - We use neutron scattering to study spin excitations in single crystals of LiFe_{0.88}Co_{0.12}As, which is located near the boundary of the superconducting phase of LiFe_{1-x}Co_{x}As and exhibits non-Fermi-liquid behavior indicative of a quantum critical point. By comparing spin excitations of LiFe_{0.88}Co_{0.12}As with a combined density functional theory and dynamical mean field theory calculation, we conclude that wave-vector correlated low energy spin excitations are mostly from the d_{xy} orbitals, while high-energy spin excitations arise from the d_{yz} and d_{xz} orbitals. Unlike most iron pnictides, the strong orbital selective spin excitations in the LiFeAs family cannot be described by an anisotropic Heisenberg Hamiltonian. While the evolution of low-energy spin excitations of LiFe_{1-x}Co_{x}As is consistent with the electron-hole Fermi surface nesting conditions for the d_{xy} orbital, the reduced superconductivity in LiFe_{0.88}Co_{0.12}As suggests that Fermi surface nesting conditions for the d_{yz} and d_{xz} orbitals are also important for superconductivity in iron pnictides. PMID- 27367402 TI - Dzyaloshinskii-Moriya Interaction as a Consequence of a Doppler Shift due to Spin Orbit-Induced Intrinsic Spin Current. AB - We present a physical picture for the emergence of the Dzyaloshinskii-Moriya (DM) interaction based on the idea of the Doppler shift by an intrinsic spin current induced by spin-orbit interaction under broken inversion symmetry. The picture is confirmed by a rigorous effective Hamiltonian theory, which reveals that the DM coefficient is given by the magnitude of the intrinsic spin current. Our approach is directly applicable to first principles calculations and clarifies the relation between the interaction and the electronic band structures. Quantitative agreement with experimental results is obtained for the skyrmion compounds Mn_{1 x}Fe_{x}Ge and Fe_{1-x}Co_{x}Ge. PMID- 27367403 TI - Quantum Walk in Degenerate Spin Environments. AB - We study the propagation of a hole in degenerate (paramagnetic) spin environments. This canonical problem has important connections to a number of physical systems, and is perfectly suited for experimental realization with ultracold atoms in an optical lattice. At the short-to-intermediate time scale that we can access using a stochastic-series-type numeric scheme, the propagation turns out to be distinctly nondiffusive with the probability distribution featuring minima in both space and time due to quantum interference, yet the motion is not ballistic, except at the beginning. We discuss possible scenarios for long-term evolution that could be explored with an unprecedented degree of detail in experiments with single-atom resolved imaging. PMID- 27367404 TI - Spin Ferroquadrupolar Order in the Nematic Phase of FeSe. AB - We provide evidence that spin ferroquadrupolar (FQ) order is the likely ground state in the nonmagnetic nematic phase of stoichiometric FeSe. By studying the variational mean-field phase diagram of a bilinear-biquadratic Heisenberg model up to the 2nd nearest neighbor, we find the FQ phase in close proximity to the columnar antiferromagnet commonly realized in iron-based superconductors; the stability of the FQ phase is further verified by the density matrix renormalization group. The dynamical spin structure factor in the FQ state is calculated with flavor-wave theory, which yields a qualitatively consistent result with inelastic neutron scattering experiments on FeSe at both low and high energies. We verify that FQ can coexist with C_{4} breaking environments in the mean-field calculation, and further discuss the possibility that quantum fluctuations in FQ act as a source of nematicity. PMID- 27367405 TI - Obtaining Highly Excited Eigenstates of Many-Body Localized Hamiltonians by the Density Matrix Renormalization Group Approach. AB - The eigenstates of many-body localized (MBL) Hamiltonians exhibit low entanglement. We adapt the highly successful density-matrix renormalization group method, which is usually used to find modestly entangled ground states of local Hamiltonians, to find individual highly excited eigenstates of MBL Hamiltonians. The adaptation builds on the distinctive spatial structure of such eigenstates. We benchmark our method against the well-studied random field Heisenberg model in one dimension. At moderate to large disorder, the method successfully obtains excited eigenstates with high accuracy, thereby enabling a study of MBL systems at much larger system sizes than those accessible to exact-diagonalization methods. PMID- 27367406 TI - Photostriction in Ferroelectrics from Density Functional Theory. AB - An ab initio procedure allowing the computation of the deformation of ferroelectric-based materials under light is presented. This numerical scheme consists in structurally relaxing the system under the constraint of a fixed n_{e} concentration of electrons photoexcited into a specific conduction band edge state from a chosen valence band state, via the use of a constrained density functional theory method. The resulting change in lattice constant along a selected crystallographic direction is then calculated for a reasonable estimate of n_{e}. This method is applied to bulk multiferroic BiFeO_{3} and predicts a photostriction effect of the same order of magnitude than the ones recently observed. A strong dependence of photostrictive response on both the reached conduction state and the crystallographic direction (along which this effect is determined) is also revealed. Furthermore, analysis of the results demonstrates that the photostriction mechanism mostly originates from the screening of the spontaneous polarization by the photoexcited electrons in combination with the inverse piezoelectric effect. PMID- 27367407 TI - Widely Tunable Single-Photon Source from a Carbon Nanotube in the Purcell Regime. AB - The narrow emission of a single carbon nanotube at low temperature is coupled to the optical mode of a fiber microcavity using the built-in spatial and spectral matching brought by this flexible geometry. A thorough cw and time-resolved investigation of the very same emitter both in free space and in cavity shows an efficient funneling of the emission into the cavity mode together with a strong emission enhancement corresponding to a Purcell factor of up to 5. At the same time, the emitted photons retain a strong sub-Poissonian statistics. By exploiting the cavity feeding effect on the phonon wings, we locked the emission of the nanotube at the cavity resonance frequency, which allowed us to tune the frequency over a 4 THz band while keeping an almost perfect antibunching. By choosing the nanotube diameter appropriately, this study paves the way to the development of carbon-based tunable single-photon sources in the telecom bands. PMID- 27367408 TI - Simulating the Radio-Frequency Dielectric Response of Relaxor Ferroelectrics: Combination of Coarse-Grained Hamiltonians and Kinetic Monte Carlo Simulations. AB - The radio-frequency dielectric response of the lead-free Ba(Zr_{0.5}Ti_{0.5})O_{3} relaxor ferroelectric is simulated using a coarse grained Hamiltonian. This concept, taken from real-space renormalization group theories, allows us to depict the collective behavior of correlated local modes gathered in blocks. Free-energy barriers for their thermally activated collective hopping are deduced from this ab initio-based approach, and used as input data for kinetic Monte Carlo simulations. The resulting numerical scheme allows us to simulate the dielectric response for external field frequencies ranging from kHz up to a few tens of MHz for the first time and to demonstrate, e.g., that local (electric or elastic) random fields lead to the dielectric relaxation in the radio-frequency range that has been observed in relaxors. PMID- 27367409 TI - Shape Transitions and Chiral Symmetry Breaking in the Energy Landscape of the Mitotic Chromosome. AB - We derive an unbiased information theoretic energy landscape for chromosomes at metaphase using a maximum entropy approach that accurately reproduces the details of the experimentally measured pairwise contact probabilities between genomic loci. Dynamical simulations using this landscape lead to cylindrical, helically twisted structures reflecting liquid crystalline order. These structures are similar to those arising from a generic ideal homogenized chromosome energy landscape. The helical twist can be either right or left handed so chiral symmetry is broken spontaneously. The ideal chromosome landscape when augmented by interactions like those leading to topologically associating domain formation in the interphase chromosome reproduces these behaviors. The phase diagram of this landscape shows that the helical fiber order and the cylindrical shape persist at temperatures above the onset of chiral symmetry breaking, which is limited by the topologically associating domain interaction strength. PMID- 27367410 TI - Broken Detailed Balance of Filament Dynamics in Active Networks. AB - Myosin motor proteins drive vigorous steady-state fluctuations in the actin cytoskeleton of cells. Endogenous embedded semiflexible filaments such as microtubules, or added filaments such as single-walled carbon nanotubes are used as novel tools to noninvasively track equilibrium and nonequilibrium fluctuations in such biopolymer networks. Here, we analytically calculate shape fluctuations of semiflexible probe filaments in a viscoelastic environment, driven out of equilibrium by motor activity. Transverse bending fluctuations of the probe filaments can be decomposed into dynamic normal modes. We find that these modes no longer evolve independently under nonequilibrium driving. This effective mode coupling results in nonzero circulatory currents in a conformational phase space, reflecting a violation of detailed balance. We present predictions for the characteristic frequencies associated with these currents and investigate how the temporal signatures of motor activity determine mode correlations, which we find to be consistent with recent experiments on microtubules embedded in cytoskeletal networks. PMID- 27367411 TI - Comment on "Line of Dirac Nodes in Hyperhoneycomb Lattices". PMID- 27367412 TI - Mullen, Uchoa, and Glatzhofer Reply. PMID- 27367413 TI - Publisher's Note: Spatial Search by Quantum Walk is Optimal for Almost All Graphs [Phys. Rev. Lett. 116, 100501 (2016)]. AB - This corrects the article DOI: 10.1103/PhysRevLett.116.100501. PMID- 27367414 TI - Erratum: Theory of Frequency-Filtered and Time-Resolved N-Photon Correlations [Phys. Rev. Lett. 109, 183601 (2012)]. AB - This corrects the article DOI: 10.1103/PhysRevLett.109.183601. PMID- 27367382 TI - Search for Violations of Lorentz Invariance and CPT Symmetry in B_{(s)}^{0} Mixing. AB - Violations of CPT symmetry and Lorentz invariance are searched for by studying interference effects in B^{0} mixing and in B_{s}^{0} mixing. Samples of B^{0} >J/psiK_{S}^{0} and B_{s}^{0}->J/psiK^{+}K^{-} decays are recorded by the LHCb detector in proton-proton collisions at center-of-mass energies of 7 and 8 TeV, corresponding to an integrated luminosity of 3 fb^{-1}. No periodic variations of the particle-antiparticle mass differences are found, consistent with Lorentz invariance and CPT symmetry. Results are expressed in terms of the standard model extension parameter Deltaa_{MU} with precisions of O(10^{-15}) and O(10^{-14}) GeV for the B^{0} and B_{s}^{0} systems, respectively. With no assumption on Lorentz (non)invariance, the CPT-violating parameter z in the B_{s}^{0} system is measured for the first time and found to be Re(z)=-0.022+/-0.033+/-0.005 and Im(z)=0.004+/-0.011+/-0.002, where the first uncertainties are statistical and the second systematic. PMID- 27367415 TI - Intraoperative monitoring of cerebral oximetry and depth of anaesthesia during neuroanesthesia procedures. AB - PURPOSE OF REVIEW: This review reports recent evidence on intraoperative monitoring of cerebral oximetry and depth of anaesthesia during neuroanaesthesia procedures. RECENT FINDINGS: The clinical benefits of intraoperative monitoring with cerebral oximetry [near infrared spectroscopy (NIRS) and brain tissue oxygenation monitoring (brptiO2)] and depth of anaesthesia with bispectral index (BIS) have recently been studied in surgical (carotid endarterectomy, cerebral arteriovenous malformations resection and brain tumour resections) and neuroradiological vascular procedures. BrptiO2/PaO2 ratio is much more reliable than absolute brptiO2 readings in detecting hypoxia in arteriovenous malformation resections. NIRS can help clinicians monitor those patients receiving endovascular treatment for acute ischaemic stroke and during carotid endarterectomy, but the value of applying cerebral oximetry in patients with cerebral vasospasm needs to be further evaluated. Awake craniotomy demonstrated that because of considerable pharmacokinetic/pharmacodynamic interindividual variation, BIS titration is recommended. Thus, the presence of a frontal brain tumour did not affect ipsilateral BIS values. SUMMARY: Recent studies provide interesting evidence of intraoperative monitoring of NIRS, brptiO2 and BIS. The brptiO2/PaO2 ratio is much more reliable than an absolute brptiO2 reading; NIRS helps clinicians to monitor patients who are undergoing endovascular treatment, and BIS guides the titration of anaesthesia during awake craniotomy; its values are not affected by the presence of a frontal brain tumour. PMID- 27367416 TI - Optic Nerve Parameters in Obese Children as Measured by Spectral Domain Optical Coherence Tomography. AB - PURPOSE: To investigate whether an association exists between obesity and optic nerve parameters. METHODS: This was a prospective comparative study including 125 eyes of 63 obese and 122 eyes of 62 healthy pediatric subjects. Optic nerve measurements were performed using the Cirrus spectral domain optical coherence tomograph (SD-OCT). RESULTS: The disc area, cup volume, mean and vertical C/D ratio, inferior and temporal RNFL thickness values were significantly higher in the control group than the obese group; however, age, sex, mean, superior and nasal RNFL thickness and rim area measurements were not statistically significantly different between the two groups. Age was significantly negatively correlated with temporal RNFL thickness in the obese group. Girls had significantly higher rim area, mean and superior RNFL thickness, and lower cup volume and vertical C/D ratio than boys in the obese group. CONCLUSION: These results could be helpful in the diagnosis and follow-up of obese children. PMID- 27367418 TI - Use of Androgen Deprivation Therapy With Radiotherapy for Intermediate- and High Risk Prostate Cancer Across the United States. PMID- 27367417 TI - Studying Dynamic Features in Myocardial Infarction Progression by Integrating miRNA-Transcription Factor Co-Regulatory Networks and Time-Series RNA Expression Data from Peripheral Blood Mononuclear Cells. AB - Myocardial infarction (MI) is a serious heart disease and a leading cause of mortality and morbidity worldwide. Although some molecules (genes, miRNAs and transcription factors (TFs)) associated with MI have been studied in a specific pathological context, their dynamic characteristics in gene expressions, biological functions and regulatory interactions in MI progression have not been fully elucidated to date. In the current study, we analyzed time-series RNA expression data from peripheral blood mononuclear cells. We observed that significantly differentially expressed genes were sharply up- or down-regulated in the acute phase of MI, and then changed slowly until the chronic phase. Biological functions involved at each stage of MI were identified. Additionally, dynamic miRNA-TF co-regulatory networks were constructed based on the significantly differentially expressed genes and miRNA-TF co-regulatory motifs, and the dynamic interplay of miRNAs, TFs and target genes were investigated. Finally, a new panel of candidate diagnostic biomarkers (STAT3 and ICAM1) was identified to have discriminatory capability for patients with or without MI, especially the patients with or without recurrent events. The results of the present study not only shed new light on the understanding underlying regulatory mechanisms involved in MI progression, but also contribute to the discovery of true diagnostic biomarkers for MI. PMID- 27367378 TI - Properties of the Binary Black Hole Merger GW150914. AB - On September 14, 2015, the Laser Interferometer Gravitational-Wave Observatory (LIGO) detected a gravitational-wave transient (GW150914); we characterize the properties of the source and its parameters. The data around the time of the event were analyzed coherently across the LIGO network using a suite of accurate waveform models that describe gravitational waves from a compact binary system in general relativity. GW150914 was produced by a nearly equal mass binary black hole of masses 36_{-4}^{+5}M_{?} and 29_{-4}^{+4}M_{?}; for each parameter we report the median value and the range of the 90% credible interval. The dimensionless spin magnitude of the more massive black hole is bound to be <0.7 (at 90% probability). The luminosity distance to the source is 410_{-180}^{+160} Mpc, corresponding to a redshift 0.09_{-0.04}^{+0.03} assuming standard cosmology. The source location is constrained to an annulus section of 610 deg^{2}, primarily in the southern hemisphere. The binary merges into a black hole of mass 62_{-4}^{+4}M_{?} and spin 0.67_{-0.07}^{+0.05}. This black hole is significantly more massive than any other inferred from electromagnetic observations in the stellar-mass regime. PMID- 27367419 TI - Fresh-Frozen Bone Allografts in Maxillary Alveolar Augmentation: Analysis of Complications, Adverse Outcomes, and Implant Survival. AB - BACKGROUND: Success of any bone augmentation procedure is dependent on several factors. Because complications occur in some cases, the aims of this study are to analyze adverse events associated with placement of fresh-frozen bone allografts (FFBAs) during alveolar ridge augmentation and to assess 1-year survival of dental implants placed in reconstructed sites. METHODS: Fifty-eight consecutive patients (15 males and 43 females, aged 38 to 76 years; mean age: 58 +/- 9.2 years) requiring maxillary bone reconstruction prior to implant placement were enrolled in this study. A total of 268 implants was subsequently placed in sites reconstructed with FFBAs. There were 22 posterior grafted sites, 19 anterior, and 17 full-arch sites. After a 4- to 6-month integration period, all patients received an implant-supported fixed prostheses. Complications occurring during treatment and the 12-month follow-up period were recorded and evaluated. RESULTS: Thirteen of 58 (22.41%) patients experienced some kind of complication in the receptor site. Infection occurred in six (10.34%) individuals, dehiscence in five (8.62%), and mucosal perforation in seven (12.07%). Adverse outcomes categorized as partial and total graft loss occurred in four (6.90%) and three (5.17%) patients, respectively. Implant failure rate was 16 (5.97%) of the 268 fixtures placed in 12 (20.70%) of 58 patients. CONCLUSIONS: Infection and suture dehiscence are significantly correlated with graft loss in a maxillary FFBA augmentation. Patients with full-arch grafting reconstructions lost significantly more implants. Early diagnosis and prompt management of adverse events seem to be of great importance in prevention of total graft loss. PMID- 27367420 TI - Risk Indicators for Periodontitis in US Adults: NHANES 2009 to 2012. AB - BACKGROUND: Through the use of optimal surveillance measures and standard case definitions, it is now possible to more accurately determine population-average risk profiles for severe (SP) and non-severe periodontitis (NSP) in adults (aged 30 years and older) in the United States. METHODS: Data from the 2009 to 2012 National Health and Nutrition Examination Survey were used, which, for the first time, used the "gold standard" full-mouth periodontitis surveillance protocol to classify severity of periodontitis following suggested Centers for Disease Control/American Academy of Periodontology case definitions. Probabilities of periodontitis by: 1) sociodemographics, 2) behavioral factors, and 3) comorbid conditions were assessed using prevalence ratios (PRs) estimated by predicted marginal probability from multivariable generalized logistic regression models. Analyses were further stratified by sex for each classification of periodontitis. RESULTS: Likelihood of total periodontitis (TP) increased with age for overall and NSP relative to non-periodontitis. Compared with non-Hispanic whites, TP was more likely in Hispanics (adjusted [a]PR = 1.38; 95% confidence interval 95% CI: 1.26 to 1.52) and non-Hispanic blacks (aPR = 1.35; 95% CI: 1.22 to 1.50), whereas SP was most likely in non-Hispanic blacks (aPR = 1.82; 95% CI: 1.44 to 2.31). There was at least a 50% greater likelihood of TP in current smokers compared with non-smokers. In males, likelihood of TP in adults aged 65 years and older was greater (aPR = 2.07; 95% CI: 1.76 to 2.43) than adults aged 30 to 44 years. This probability was even greater in women (aPR = 3.15; 95% CI: 2.63 to 3.77). Likelihood of TP was higher in current smokers relative to non-smokers regardless of sex and periodontitis classification. TP was more likely in men with uncontrolled diabetes mellitus (DM) compared with adults without DM. CONCLUSIONS: Assessment of risk profiles for periodontitis in adults in the United States based on gold standard periodontal measures show important differences by severity of disease and sex. Cigarette smoking, specifically current smoking, remains an important modifiable risk for all levels of periodontitis severity. Higher likelihood of TP in older adults and in males with uncontrolled DM is noteworthy. These findings could improve identification of target populations for effective public health interventions to improve periodontal health of adults in the United States. PMID- 27367383 TI - First Observation of D^{0}-D[over -]^{0} Oscillations in D^{0}->K^{+}pi^{ }pi^{+}pi^{-} Decays and Measurement of the Associated Coherence Parameters. AB - Charm meson oscillations are observed in a time-dependent analysis of the ratio of D^{0}->K^{+}pi^{-}pi^{+}pi^{-} to D^{0}->K^{-}pi^{+}pi^{-}pi^{+} decay rates, using data corresponding to an integrated luminosity of 3.0 fb^{-1} recorded by the LHCb experiment. The measurements presented are sensitive to the phase-space averaged ratio of doubly Cabibbo-suppressed to Cabibbo-favored amplitudes r_{D}^{K3pi} and the product of the coherence factor R_{D}^{K3pi} and a charm mixing parameter y_{K3pi}^{'}. The constraints measured are r_{D}^{K3pi}=(5.67+/ 0.12)*10^{-2}, which is the most precise determination to date, and R_{D}^{K3pi}y_{K3pi}^{'}=(0.3+/-1.8)*10^{-3}, which provides useful input for determinations of the CP-violating phase gamma in B^{+/-}->DK^{+/-}, D >K^{?}pi^{+/-}pi^{?}pi^{+/-} decays. The analysis also gives the most precise measurement of the D^{0}->K^{+}pi^{-}pi^{+}pi^{-} branching fraction, and the first observation of D^{0}-D[over -]^{0} oscillations in this decay mode, with a significance of 8.2 standard deviations. PMID- 27367423 TI - Changes in Periodontal Parameters and C-Reactive Protein After Pregnancy. AB - BACKGROUND: This study assesses hormonal, inflammatory, and periodontal changes in pregnant women and postpartum in the absence of periodontal treatment, and seeks to determine any correlations among these parameters. METHODS: A longitudinal, observational study of 117 pregnant women (aged 23 to 42 years) was undertaken in a private gynecologic center between weeks 32 and 35 of pregnancy and 6 to 8 weeks after delivery. Levels of progesterone and C-reactive protein (CRP) in plasma were determined, as well as periodontal indices, including: 1) plaque index (PI); 2) bleeding on probing (BOP); 3) probing depth (PD); and 4) clinical attachment level (CAL). RESULTS: Postpartum progesterone and CRP declined sharply from 90.85 +/- 42.51 ng/mL and 3.73 +/- 4.01 mg/L to 0.77 +/- 1.43 ng/mL and 1.43 +/- 1.67 mg/L, respectively. There was also a significant improvement in all periodontal indices (P <0.05) with the exception of PI. During pregnancy mean BOP was 21.03%, mean PD 2.62 mm, and mean CAL 1.20 mm. After delivery mean BOP was 13.25%, mean PD 2.39 mm, and mean CAL 1.14 mm. Percentage of 1- to 3-mm pockets increased (P <0.05), while 4- to 5-mm pockets and pockets >6 mm decreased significantly (P <0.001). Reduction in CRP correlated significantly with decrease in BOP (P <0.001). CONCLUSIONS: Postpartum, there was a dramatic reduction in progesterone and CRP, together with an improvement in BOP, PD, and CAL in the absence of periodontal treatment. Decrease in CRP was related to an improvement in periodontal bleeding. PMID- 27367422 TI - Effectiveness of Computer-Based Training on Toothbrush Skills of Patients Treated With Crowns: A Randomized Controlled Trial. AB - BACKGROUND: This study was conducted to assess plaque removal skills in patients with fixed dental prostheses (FDP), and effectiveness of computer-based training (CBT) of different brushing techniques (Fones versus Bass technique in their common modifications). METHODS: Ninety-three patients with FDP were randomly allocated to one of three training groups: 1) C (control group); 2) F (Fones technique group); and 3) B (Bass technique group). All patients received CBT of the basics of toothbrushing. Group C received no further instructions while groups F and B received additional CBT of the modified Fones or the modified Bass technique, respectively. Plaque levels were assessed immediately after patients had been asked to perform oral hygiene to the best of their abilities. RESULTS: Prior to training, persistent plaque deposits were found at 80% of marginal sites of natural teeth immediately after patients had performed oral hygiene. Considerably fewer plaque deposits were found on FDP (43%). No significant group differences were observed 6 and 12 weeks after training, either for natural teeth or for FDP (all P >0.05). CONCLUSIONS: Plaque removal skills are low in patients with FDP. Apparently, they do not profit from CBT of the techniques studied here. Studies observing their actual brushing behavior should be conducted to elucidate reasons for their deficits and to explore why CBT does not work in this group of patients. PMID- 27367421 TI - A Two-Domain Self-Report Measure of Periodontal Disease Has Good Accuracy for Periodontitis Screening in Dental School Outpatients. AB - BACKGROUND: The assessment of periodontitis and treatment needs is primarily based on clinical and radiographic examinations. Albeit effective in predicting treatment needs, these examinations are costly, time-consuming, and impractical for assessing population-level needs. The purpose of the present study is to evaluate a two-domain self-report questionnaire for rapid periodontitis screening. METHODS: Six hundred white adult individuals, dentate or partially dentate and seeking dental therapy at a university clinic, underwent oral examination utilizing the full-mouth Community Periodontal Index of Treatment Needs (CPITN). To assess predictive value of self-reported periodontal measures (SRPMs) for periodontitis screening, four questions were formulated. Two questions aimed to assess "dentist-diagnosed periodontal disease" and two inquired about "self-assessed periodontitis." Multiple logistic regression models were used to construct receiver-operating characteristic curves, and predictor selection was performed via a forward stepwise selection process. RESULTS: Five hundred thirty-five volunteers with a mean age of 50.1 years elected to respond to SRPMs via telephone interview. After oral examination, 17.8% of participants were assessed as having CPITN = 4, representing compromised periodontal status. Sensitivity and specificity for correctly classifying compromised periodontal status ranged from 5.3% to 72.6%, and 87.8% to 99.5% for individual SRPMs. Sensitivity and specificity were increased when combining a measure of self assessed periodontal disease and a measure of dentist-diagnosed disease as predictors. Addition of age and sex maximized sensitivity/specificity at 82.1%/82.2%. Diabetic status, smoking, and body mass index did not enhance the prediction. CONCLUSIONS: A two-domain self-report measure combining two self report items with age and sex has good sensitivity and specificity for periodontitis screening in a white, university-based population. The proposed self-report measure can be valuable for periodontitis screening in resource limited settings where gold standard clinical examination may not be pragmatic. Further validation studies are required to assess whether findings from this study are context-specific. PMID- 27367424 TI - Laser speckle contrast imaging is sensitive to advective flux. AB - Unlike laser Doppler flowmetry, there has yet to be presented a clear description of the physical variables that laser speckle contrast imaging (LSCI) is sensitive to. Herein, we present a theoretical basis for demonstrating that LSCI is sensitive to total flux and, in particular, the summation of diffusive flux and advective flux. We view LSCI from the perspective of mass transport and briefly derive the diffusion with drift equation in terms of an LSCI experiment. This equation reveals the relative sensitivity of LSCI to both diffusive flux and advective flux and, thereby, to both concentration and the ordered velocity of the scattering particles. We demonstrate this dependence through a short series of flow experiments that yield relationships between the calculated speckle contrast and the concentration of the scatterers (manifesting as changes in scattering coefficient), between speckle contrast and the velocity of the scattering fluid, and ultimately between speckle contrast and advective flux. Finally, we argue that the diffusion with drift equation can be used to support both Lorentzian and Gaussian correlation models that relate observed contrast to the movement of the scattering particles and that a weighted linear combination of these two models is likely the most appropriate model for relating speckle contrast to particle motion. PMID- 27367425 TI - Improving Fishing Pattern Detection from Satellite AIS Using Data Mining and Machine Learning. AB - A key challenge in contemporary ecology and conservation is the accurate tracking of the spatial distribution of various human impacts, such as fishing. While coastal fisheries in national waters are closely monitored in some countries, existing maps of fishing effort elsewhere are fraught with uncertainty, especially in remote areas and the High Seas. Better understanding of the behavior of the global fishing fleets is required in order to prioritize and enforce fisheries management and conservation measures worldwide. Satellite-based Automatic Information Systems (S-AIS) are now commonly installed on most ocean going vessels and have been proposed as a novel tool to explore the movements of fishing fleets in near real time. Here we present approaches to identify fishing activity from S-AIS data for three dominant fishing gear types: trawl, longline and purse seine. Using a large dataset containing worldwide fishing vessel tracks from 2011-2015, we developed three methods to detect and map fishing activities: for trawlers we produced a Hidden Markov Model (HMM) using vessel speed as observation variable. For longliners we have designed a Data Mining (DM) approach using an algorithm inspired from studies on animal movement. For purse seiners a multi-layered filtering strategy based on vessel speed and operation time was implemented. Validation against expert-labeled datasets showed average detection accuracies of 83% for trawler and longliner, and 97% for purse seiner. Our study represents the first comprehensive approach to detect and identify potential fishing behavior for three major gear types operating on a global scale. We hope that this work will enable new efforts to assess the spatial and temporal distribution of global fishing effort and make global fisheries activities transparent to ocean scientists, managers and the public. PMID- 27367427 TI - Clarifying Scar Revision Techniques and Their Proper Use. PMID- 27367426 TI - Identification of Shell Colour Pigments in Marine Snails Clanculus pharaonius and C. margaritarius (Trochoidea; Gastropoda). AB - Colour and pattern are key traits with important roles in camouflage, warning and attraction. Ideally, in order to begin to understand the evolution and ecology of colour in nature, it is important to identify and, where possible, fully characterise pigments using biochemical methods. The phylum Mollusca includes some of the most beautiful exemplars of biological pigmentation, with the vivid colours of sea shells particularly prized by collectors and scientists alike. Biochemical studies of molluscan shell colour were fairly common in the last century, but few of these studies have been confirmed using modern methods and very few shell pigments have been fully characterised. Here, we use modern chemical and multi-modal spectroscopic techniques to identify two porphyrin pigments and eumelanin in the shell of marine snails Clanculus pharaonius and C margaritarius. The same porphyrins were also identified in coloured foot tissue of both species. We use high performance liquid chromatography (HPLC) to show definitively that these porphyrins are uroporphyrin I and uroporphyrin III. Evidence from confocal microscopy analyses shows that the distribution of porphyrin pigments corresponds to the striking pink-red of C. pharaonius shells, as well as pink-red dots and lines on the early whorls of C. margaritarius and yellow-brown colour of later whorls. Additional HPLC results suggest that eumelanin is likely responsible for black spots. We refer to the two differently coloured porphyrin pigments as trochopuniceus (pink-red) and trochoxouthos (yellow-brown) in order to distinguish between them. Trochopuniceus and trochoxouthos were not found in the shell of a third species of the same superfamily, Calliostoma zizyphinum, despite its superficially similar colouration, suggesting that this species has different shell pigments. These findings have important implications for the study of colour and pattern in molluscs specifically, but in other taxa more generally, since this study shows that homology of visible colour cannot be assumed without identification of pigments. PMID- 27367379 TI - GW151226: Observation of Gravitational Waves from a 22-Solar-Mass Binary Black Hole Coalescence. AB - We report the observation of a gravitational-wave signal produced by the coalescence of two stellar-mass black holes. The signal, GW151226, was observed by the twin detectors of the Laser Interferometer Gravitational-Wave Observatory (LIGO) on December 26, 2015 at 03:38:53 UTC. The signal was initially identified within 70 s by an online matched-filter search targeting binary coalescences. Subsequent off-line analyses recovered GW151226 with a network signal-to-noise ratio of 13 and a significance greater than 5sigma. The signal persisted in the LIGO frequency band for approximately 1 s, increasing in frequency and amplitude over about 55 cycles from 35 to 450 Hz, and reached a peak gravitational strain of 3.4_{-0.9}^{+0.7}*10^{-22}. The inferred source-frame initial black hole masses are 14.2_{-3.7}^{+8.3}M_{?} and 7.5_{-2.3}^{+2.3}M_{?}, and the final black hole mass is 20.8_{-1.7}^{+6.1}M_{?}. We find that at least one of the component black holes has spin greater than 0.2. This source is located at a luminosity distance of 440_{-190}^{+180} Mpc corresponding to a redshift of 0.09_{-0.04}^{+0.03}. All uncertainties define a 90% credible interval. This second gravitational-wave observation provides improved constraints on stellar populations and on deviations from general relativity. PMID- 27367428 TI - Loneliness, Depression, and Inflammation: Evidence from the Multi-Ethnic Study of Atherosclerosis. AB - OBJECTIVE: Both objective and subjective aspects of social isolation have been associated with alterations in immune markers relevant to multiple chronic diseases among older adults. However, these associations may be confounded by health status, and it is unclear whether these social factors are associated with immune functioning among relatively healthy adults. The goal of this study was to examine the associations between perceived loneliness and circulating levels of inflammatory markers among a diverse sample of adults. METHODS: Data come from a subset of the Multi-Ethnic Study of Atherosclerosis (n = 441). Loneliness was measured by three items derived from the UCLA Loneliness Scale. The association between loneliness and C-reactive protein (CRP) and fibrinogen was assessed using multivariable linear regression analyses. Models were adjusted for demographic and health characteristics. RESULTS: Approximately 50% of participants reported that they hardly ever felt lonely and 17.2% felt highly lonely. Individuals who were unmarried/unpartnered or with higher depressive symptoms were more likely to report being highly lonely. There was no relationship between perceived loneliness and ln(CRP) (beta = -0.051, p = 0.239) adjusting for demographic and health characteristics. Loneliness was inversely associated with ln(fibrinogen) (beta = -0.091, p = 0.040), although the absolute magnitude of this relationship was small. CONCLUSION: These results indicate that loneliness is not positively associated with fibrinogen or CRP among relatively healthy middle-aged adults. PMID- 27367431 TI - 'Entrustable professional activities': the way to go for competency-based curriculum? PMID- 27367430 TI - Influence of particle shedding from silicone tubing on antibody stability. AB - OBJECTIVES: Peristaltic pumps are increasingly employed during fill & finish operations of a biopharmaceutical drug, due to sensitivity of many biological products to rotary piston pump-related stresses. Yet, possibly also unit operations using peristaltic pumps may shed particulates into the final product due to abrasion from the employed tubing. It was the aim of this study to elucidate the potential influence of particles shed from peristaltic pump tubing on the stability of a drug product. METHODS: Spiking solutions containing shed silicone particles were prepared via peristaltic pumping of placebo under recirculating conditions and subsequently characterized. Two formulated antibodies were spiked with two realistic, but worst-case levels of particles and a 6-month accelerated stability study with storage at 2-8, 25 and 40 degrees C were conducted. KEY FINDINGS: Regarding the formation of aggregates and fragments, both mAbs degraded at their typically expected rates and no additional impact of spiked particles was observed. No changes were discerned however in turbidity, subvisible and visible particle assessments. Flow imaging data for one of the mAb formulations with spiked particles suggested limited colloidal stability of shed particles as indicated by a similar increase in spiked placebo. CONCLUSIONS: Shed silicone particles from peristaltic pump tubing are assumed to not impair drug product stability. PMID- 27367429 TI - Antagonist activity of the antipsychotic drug lithium chloride and the antileukemic drug imatinib mesylate during glioblastoma treatment in vitro. AB - OBJECTIVES: Glioblastoma (GBM), the most common primary tumour of the central nervous system, is characterised by a high malignancy and poor prognosis. The aims of this study were to investigate whether the combination of imatinib mesylate (IM) and lithium chloride (LiCl) exhibited a synergistic effect in treatment and to determine whether midkine (MK) affected the fate of this treatment in vitro. METHODS: Monolayer and spheroid cultures of the T98G human GBM cell line were treated with an IM and LiCl combination for 72 h. The cell proliferation index, apoptotic index, cell cycle distribution, apoptotic and anti apoptotic protein levels, and cAMP level as well as the cellular morphology and ultrastructure were evaluated. RESULTS: All applications inhibited cell proliferation and induced apoptosis. The most substantial decreases in cell proliferation and the caspase-3, epidermal growth factor receptor (EGFR), platelet derived growth factor receptor-alpha (PDGFR-alpha), multidrug resistance protein-1 (MRP-1), aquaporin-4 (AQP-4) and cAMP levels were induced by the LiCl treatment, which exhibited more pronounced effects compared with the combination treatment. LiCl was less effective in decreasing the MK and B cell lymphoma-2 (Bcl-2) levels compared with the combination treatment. The most substantial decrease in the p170 levels was identified following the combination treatment, whereas IM induced the second greatest decrease. LiCl alone had no effect on the p170 levels. IM induced the most substantial decrease in the phospho-glycogen synthase kinase 3-beta (p-GSK-3beta)/glycogen synthase kinase 3-beta (GSK-3beta) ratio, and LiCl induced the second most substantial decrease. Both LiCl and the combination treatment induced G2 + M arrest, whereas IM induced G0 + G1 arrest after 72 h of exposure. An apoptotic appearance and autophagic vacuoles were commonly identified in the LiCl, combination and IM groups, respectively. CONCLUSIONS: The combination of IM and LiCl exhibited an antagonist effect, and MK had a role at this antagonism. PMID- 27367433 TI - Effect of Different Surfactants on the Interfacial Behavior of the n-Hexane-Water System in the Presence of Silica Nanoparticles. AB - This paper presents the effect of negatively charged silica nanoparticles (NPs) on the interfacial tension of the n-hexane-water system at variable concentrations of four different surfactants, viz., an anionic surfactant, sodium dodecyl sulfate (SDS), a cationic surfactant, cetyltrimethylammonium bromide (CTAB), and two nonionic surfactants, Tween 20 and Triton X-100 (TX-100). The presence of negatively charged silica nanoparticles is found to have a different effect depending on the type of surfactant. In the case of ionic surfactants, SDS and CTAB, silica NPs reduce the interfacial tension of the system. On the contrary, for nonionic surfactants, Tween 20 and TX-100, silica NPs increase the interfacial tension. The increasing/decreasing nature of the interfacial tension in the presence of NPs is well supported by the calculated surface excess concentrations. The diffusion kinetic control (DKC) and statistical rate theory (SRT) models are used to understand the behavior of dynamic interfacial tension of the surfactant-NP-oil-water system. The DKC model is found to describe the studied surfactant-NP-oil-water systems more aptly. PMID- 27367432 TI - Simulation-based medical education training improves short and long-term competency in, and knowledge of central venous catheter insertion: A before and after intervention study. AB - BACKGROUND: Multimodal educational interventions have been shown to improve short term competency in, and knowledge of central venous catheter (CVC) insertion. OBJECTIVE: To evaluate the effectiveness of simulation-based medical education training in improving short and long-term competency in, and knowledge of CVC insertion. DESIGN: Before and after intervention study. SETTING: University Geneva Hospital, Geneva, Switzerland, between May 2008 and January 2012. PARTICIPANTS: Residents in anaesthesiology aware of the Seldinger technique for vascular puncture. INTERVENTION: Participants attended a half-day course on CVC insertion. Learning objectives included work organization, aseptic technique and prevention of CVC complications. CVC insertion competency was tested pretraining, posttraining and then more than 2 years after training (sustainability phase). MAIN OUTCOME MEASURES: The primary study outcome was competency as measured by a global rating scale of technical skills, a hand hygiene compliance score and a checklist compliance score. Secondary outcome was knowledge as measured by a standardised pretraining and posttraining multiple-choice questionnaire. Statistical analyses were performed using paired Student's t test or Wilcoxon signed-rank test. RESULTS: Thirty-seven residents were included; 18 were tested in the sustainability phase (on average 34 months after training). The average global rating of skills was 23.4 points (+/-SD 4.08) before training, 32.2 (+/ 4.51) after training (P < 0.001 for comparison with pretraining scores) and 26.5 (+/-5.34) in the sustainability phase (P = 0.040 for comparison with pretraining scores). The average hand hygiene compliance score was 2.8 (+/-1.0) points before training, 5.0 (+/-1.04) after training (P < 0.001 for comparison with pretraining scores) and 3.7 (+/-1.75) in the sustainability phase (P = 0.038 for comparison with pretraining scores). The average checklist compliance was 14.9 points (+/ 2.3) before training, 19.9 (+/-1.06) after training (P < 0.001 for comparison with pretraining scores) and 17.4 (+/-1.41) (P = 0.002 for comparison with pretraining scores). The percentage of correct answers in the multiple-choice questionnaire increased from 76.0% (+/-7.9) before training to 87.7% (+/-4.4) after training (P < 0.001). CONCLUSION: Simulation-based medical education training was effective in improving short and long-term competency in, and knowledge of CVC insertion. PMID- 27367434 TI - Designing and examining e-waste recycling process: methodology and case studies. AB - Increasing concerns on resource depletion and environmental pollution have largely obliged electrical and electronic waste (e-waste) should be tackled in an environmentally sound manner. Recycling process development is regarded as the most effective and fundamental to solve the e-waste problem. Based on global achievements related to e-waste recycling in the past 15 years, we first propose a theory to design an e-waste recycling process, including measuring e-waste recyclability and selection of recycling process. And we summarize the indicators and tools in terms of resource dimension, environmental dimension, and economic dimension, to examine the e-waste recycling process. Using the sophisticated experience and adequate information of e-waste management, spent lithium-ion batteries and waste printed circuit boards are chosen as case studies to implement and verify the proposed method. All the potential theory and obtained results in this work can contribute to future e-waste management toward best available techniques and best environmental practices. PMID- 27367435 TI - Layered-to-Tunnel Structure Transformation and Oxygen Redox Chemistry in LiRhO2 upon Li Extraction and Insertion. AB - Layered Li(M,Li)O2 (where M is a transition metal) ordered rock-salt-type structures are used in advanced metal-ion batteries as one of the best hosts for the reversible intercalation of Li ions. Besides the conventional redox reaction involving oxidation/reduction of the M cation upon Li extraction/insertion, creating oxygen-located holes because of the partial oxygen oxidation increases capacity while maintaining the oxidized oxygen species in the lattice through high covalency of the M-O bonding. Typical degradation mechanism of the Li(M,Li)O2 electrodes involves partially irreversible M cation migration toward the Li positions, resulting in gradual capacity/voltage fade. Here, using LiRhO2 as a model system (isostructural and isoelectronic to LiCoO2), for the first time, we demonstrate an intimate coupling between the oxygen redox and M cation migration. A formation of the oxidized oxygen species upon electrochemical Li extraction coincides with transformation of the layered Li1-xRhO2 structure into the gamma-MnO2-type rutile-ramsdellite intergrowth LiyRh3O6 structure with rutile like [1 * 1] channels along with bigger ramsdellite-like [2 * 1] tunnels through massive and concerted Rh migration toward the empty positions in the Li layers. The oxidized oxygen dimers with the O-O distances as short as 2.26 A are stabilized in this structure via the local Rh-O configuration reminiscent to that in the MU-peroxo-MU-hydroxo Rh complexes. The LiyRh3O6 structure is remarkably stable upon electrochemical cycling illustrating that proper structural implementation of the oxidized oxygen species can open a pathway toward deliberate employment of the anion redox chemistry in high-capacity/high-voltage positive electrodes for metal-ion batteries. PMID- 27367437 TI - The History of Neuro-Ophthalmology in Chile. PMID- 27367438 TI - What does normal tendon structure look like? New insights into tissue characterization in the Achilles tendon. AB - Recently, ultrasound tissue characterization (UTC) was introduced as a reliable method for quantification of tendon structure. Despite increasing publications on the use of UTC, it is striking that there is a lack of normative data in active adolescents. Therefore, the aim of this study was to provide normative values of the Achilles tendon as quantified by UTC. Seventy physiotherapy students (26 male and 44 female students) with no history of Achilles tendon injuries were recruited. The Achilles tendons were scanned with UTC to characterize tendon structure. This study demonstrated that Achilles tendons of active, healthy adolescents contained 54.6% echo type I, 42.8% echo type II, 2.2% echo type III, and 0.3% echo type IV at midportion. The comparison between insertion and midportion of the tendon showed more echo type II at insertion (P < 0.001). Furthermore, female tendons contained significantly more echo type II, in both insertion and midportion compared with male tendons (P = 0.004 and P = 0.003, respectively). The results of this study, with respect to the MDC (minimum detectable change), highlight differences in the UTC echopattern in the normal population (sex and regional location), which are important considerations for future studies. PMID- 27367436 TI - Estimations and predictors of non-compliance in switchers to reduced nicotine content cigarettes. AB - BACKGROUND AND AIMS: Clinical trials on the impact and safety of reduced nicotine content cigarettes (RNCs) are ongoing, and an important methodological concern is participant compliance with smoking only RNCs. Our aims were to measure non compliance biochemically with urine cotinine (COT) and total nicotine equivalents (TNEs), compare with self-reported non-compliance and identify associated covariates. DESIGN: Secondary analysis of a double-blind, parallel, randomized clinical trial. SETTING: Research centers from the United States, enrolling participants from June 2013 to July 2014. PARTICIPANTS: Volunteer sample of 242 participants (55% Caucasian), average age of 41.2 years, smoking at least five cigarettes per day (CPD). INTERVENTION: Smoking very low nicotine cigarettes (VLNCs; 0.4 mg nicotine/g tobacco) for 6 weeks. MEASUREMENTS: The primary outcome was biochemically verified non-compliance, measured as thresholds of COT/CPD and TNE/CPD ratios, considering changes in nicotine content from conventional levels to VLNCs, and as an absolute threshold of week 6 TNEs. Self-reported non compliance was measured via daily phone calls. Key predictors included age, sex, race, menthol preference, nicotine metabolite ratio, time to first cigarette, dependence, CPD, TNEs, tar level and cigarette evaluation. FINDINGS: Estimates of non-compliance with smoking the VLNCs exclusively include: the biochemical ratios (both 78%), the week 6 TNE threshold (76%) and self-report (39%). Of the key covariates, age, dependence and cigarette evaluations of satisfaction were significant; for age, younger participants more likely to be non-compliant [P = 0.01; odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.96-0.99]. Dependence was associated significantly with self-reported non-compliance (P = 0.01; OR = 1.28, 95% CI = 1.06-1.55). Cigarette evaluations of satisfaction were associated significantly with non-compliance (P = 0.001; OR = 0.71, 95% CI = 0.61 0.82). CONCLUSIONS: Among smokers volunteering to smoke only very low nicotine cigarettes for 6 weeks, non-compliance was common and biochemical assessments detected more cases of non-compliance than self-report. Despite high levels of non-compliance, smokers reduced their intake of nicotine by an average of 60%. PMID- 27367439 TI - The Indirect Effect of Source Information on Psychological Reactance Against Antismoking Messages Through Perceived Bias. AB - This study investigates the indirect effect of source information on attitudes toward antismoking campaigns through perceived bias and psychological reactance by employing a survey experiment (N = 416). Findings demonstrate that an editorial advocating antismoking campaigns from ideologically congruent media is perceived as less biased than the same editorial from hostile media. The perceived bias is linked to perceived threat to freedom, which, in turn, is linked to psychological reactance against the editorial, resulting in less favorable attitudes toward antismoking campaigns. Smokers are more likely to show the linkages than nonsmokers. Implications of the findings are discussed. PMID- 27367440 TI - As Walking Movement Grows, Neighborhood Walkability Gains Attention. PMID- 27367441 TI - Assessment of Normal Eyeball Protrusion Using Computed Tomographic Imaging and Three-Dimensional Reconstruction in Korean Adults. AB - PURPOSE: The aim of the present study was to assess normal eyeball protrusion from the orbital rim using two- and three-dimensional images and demonstrate the better suitability of CT images for assessment of exophthalmos. METHODS: The facial computed tomographic (CT) images of Korean adults were acquired in sagittal and transverse views. The CT images were used in reconstructing three dimensional volume of faces using computer software. The protrusion distances from orbital rims and the diameters of eyeballs were measured in the two views of the CT image and three-dimensional volume of the face. Relative exophthalmometry was calculated by the difference in protrusion distance between the right and left sides. RESULTS: The eyeball protrusion was 4.9 and 12.5 mm in sagittal and transverse views, respectively. The protrusion distances were 2.9 mm in the three dimensional volume of face. There were no significant differences between right and left sides in the degree of protrusion, and the difference was within 2 mm in more than 90% of the subjects. CONCLUSIONS: The results of the present study will provide reliable criteria for precise diagnosis and postoperative monitoring using CT imaging of diseases such as thyroid-associated ophthalmopathy and orbital tumors. PMID- 27367442 TI - Peripheral ligands as electron storage reservoirs and their role in enhancement of photocatalytic hydrogen generation. AB - The contrasting early-time photodynamics of two related Ru/Pt photocatalysts with very different photocatalytic H2 generation capabilities are reported. Ultrafast equilibration (535 +/- 17 fs) creates an electron reservoir on the peripheral ligands of the ester substituted complex, allowing a dramatic increase in photocatalytic performance. This insight opens the way towards a novel design strategy for H2 generating molecular photocatalysts. PMID- 27367443 TI - Performance-Enhancing Asymmetric Separator for Lithium-Sulfur Batteries. AB - Asymmetric separators with polysulfide barrier properties consisting of porous polypropylene grafted with styrenesulfonate (PP-g-PLiSS) were characterized in lithium-sulfur cells to assess their practical applicability. Galvanostatic cycling at different C-rates with and without an electrolyte additive and cyclic voltammetry were used to probe the electrochemical performance of the cells with the PP-g-PLiSS separators and to compare it with the performance of the cells utilizing state-of-the-art separator, Celgard 2400. Overall, it was found that regardless of the applied cycling rate, the use of the grafted separators greatly enhances the Coulombic efficiency of the cell. An appropriate Li-exchange-site ( SO3(-)) concentration at and near the surface of the separator was found to be essential to effectively suppress the polysulfide shuttle without sacrificing the Li-ion mobility through the separator and to improve the practical specific charge of the cell. PMID- 27367444 TI - The promise of adaptive radiotherapy for pelvic tumors: "too high cost for too little result" or "a low cost for a significant result"? PMID- 27367445 TI - Cellular Interrogation: Exploiting Cell-to-Cell Variability to Discriminate Regulatory Mechanisms in Oscillatory Signalling. AB - The molecular complexity within a cell may be seen as an evolutionary response to the external complexity of the cell's environment. This suggests that the external environment may be harnessed to interrogate the cell's internal molecular architecture. Cells, however, are not only nonlinear and non stationary, but also exhibit heterogeneous responses within a clonal, isogenic population. In effect, each cell undertakes its own experiment. Here, we develop a method of cellular interrogation using programmable microfluidic devices which exploits the additional information present in cell-to-cell variation, without requiring model parameters to be fitted to data. We focussed on Ca2+ signalling in response to hormone stimulation, which exhibits oscillatory spiking in many cell types and chose eight models of Ca2+ signalling networks which exhibit similar behaviour in simulation. We developed a nonlinear frequency analysis for non-stationary responses, which could classify models into groups under parameter variation, but found that this question alone was unable to distinguish critical feedback loops. We further developed a nonlinear amplitude analysis and found that the combination of both questions ruled out six of the models as inconsistent with the experimentally-observed dynamics and heterogeneity. The two models that survived the double interrogation were mathematically different but schematically identical and yielded the same unexpected predictions that we confirmed experimentally. Further analysis showed that subtle mathematical details can markedly influence non-stationary responses under parameter variation, emphasising the difficulty of finding a "correct" model. By developing questions for the pathway being studied, and designing more versatile microfluidics, cellular interrogation holds promise as a systematic strategy that can complement direct intervention by genetics or pharmacology. PMID- 27367446 TI - Identification of five pyrrolidinyl substituted cathinones and the collision induced dissociation of electrospray-generated pyrrolidinyl substituted cathinones. AB - This article reports on the analytical properties of five pyrrolidinyl substituted cathinones: alpha-pyrrolidinononaphenone (alpha-PNP, 1), 4-chloro alpha-pyrrolidinopropiophenone (4-Cl-alpha-PPP, 2), 4-chloro-alpha pyrrolidinovalerophenone (4-Cl-alpha-PVP, 3), 5-dihydrobenzofuranpyrovalerone (5 DBFPV, 4), and 2-(pyrrolidin-1-yl)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)hexan-1 one (beta-THNPH, 5). These identifications were based on liquid chromatography quadrupole time-of-flight-mass spectrometry (LC-QTOF-MS), gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR). To our knowledge, no analytical data about alpha-PNP, 4-Cl-alpha-PPP, 4-Cl-alpha-PVP, and beta-THNPH have appeared until now, making this the first report on these compounds. Moreover, in order to study the collision-induced dissociation (CID) characteristic fragmentation routes of pyrrolidinyl substituted cathinones, a total number of 13 pyrrolidinyl substituted cathinones were selected and discussed. The major fragmentation pathways under CID mode are produced, leading to the formation of characteristic ions. Product ions of [M-C4 H9 N]+ and Cn H2n N+ indicate the presence of pyrrolidinyl substitution. Characteristic fragments are also produced via the cleavages of the CH-N(CH2 )4 bond and the CO-CHN bond. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27367447 TI - Development of Kinematic Graphs of Median Nerve during Active Finger Motion: Implications of Smartphone Use. AB - BACKGROUND: Certain hand activities cause deformation and displacement of the median nerve at the carpal tunnel due to the gliding motion of tendons surrounding it. As smartphone usage escalates, this raises the public's concern whether hand activities while using smartphones can lead to median nerve problems. OBJECTIVE: The aims of this study were to 1) develop kinematic graphs and 2) investigate the associated deformation and rotational information of median nerve in the carpal tunnel during hand activities. METHODS: Dominant wrists of 30 young adults were examined with ultrasonography by placing a transducer transversely on their wrist crease. Ultrasound video clips were recorded when the subject performing 1) thumb opposition with the wrist in neutral position, 2) thumb opposition with the wrist in ulnar deviation and 3) pinch grip with the wrist in neutral position. Six still images that were separated by 0.2-second intervals were then captured from the ultrasound video for the determination of 1) cross-sectional area (CSA), 2) flattening ratio (FR), 3) rotational displacement (RD) and 4) translational displacement (TD) of median nerve in the carpal tunnel, and these collected information of deformation, rotational and displacement of median nerve were compared between 1) two successive time points during a single hand activity and 2) different hand motions at the same time point. Finally, kinematic graphs were constructed to demonstrate the mobility of median nerve during different hand activities. RESULTS: Performing different hand activities during this study led to a gradual reduction in CSA of the median nerve, with thumb opposition together with the wrist in ulnar deviation causing the greatest extent of deformation of the median nerve. Thumb opposition with the wrist in ulnar deviation also led to the largest extent of TD when compared to the other two hand activities of this study. Kinematic graphs showed that the motion pathways of median nerve during different hand activities were complex. CONCLUSION: We observed that the median nerve in the carpal tunnel was rotated, deformed and displaced during the hand activities that people may be performed when using a smartphone, suggesting an increased risk of carpal tunnel syndrome (CTS). In addition, the kinematic graphs of median nerve developed in the present study provide new clues for further studies on the pathophysiology of CTS, and alerting smartphone users to establish proper postural habits when using handheld electronic devices. PMID- 27367448 TI - Successful use of Hemospray as a bridge to surgery in life-threatening bleeding from a gastrointestinal stromal tumor of the stomach. PMID- 27367449 TI - Submucosal tunneling endoscopic resection for multiple esophageal leiomyomas. PMID- 27367450 TI - Endoscopic treatment of recurrent sigmoid volvulus with colopexy assisted by T fasteners and colostomy. PMID- 27367451 TI - Acute pancreatitis after endoscopic biopsy of the minor duodenal papilla in an individual with pancreas divisum. PMID- 27367452 TI - Riser pattern is a predictor of kidney mortality among patients with chronic kidney disease. AB - BACKGROUND: Hypertension is a crucial risk factor for cardiovascular death and loss of residual kidney function. Absence of the nocturnal decline in blood pressure (BP) predicts cardiovascular events and poor prognosis. However, characteristics of hypertension in moderate-to-severe chronic kidney disease (CKD) have not been fully evaluated. We aimed to assess the circadian variation of BP and kidney survival in CKD patients. METHODS: Patients who were examined by 24-h ambulatory BP monitoring (ABPM) and estimated glomerular filtration rate (eGFR), <45 ml/min/1.73 m(2), were enrolled in the study. The impacts of BP circadian rhythm and brain natriuretic peptide (BNP) on kidney survival were evaluated. RESULTS: A total of 124 patients were enrolled. The average age was 64 +/- 14 years, 57% were male, and 43% had diabetes. Forty-five percent of patients had a non-dipper pattern, 35% had a riser pattern, 19% had a dipper pattern, and 1% had an extreme-dipper pattern. The prevalence of diabetes and plasma BNP levels was higher and eGFR was lower in the riser-pattern group than in the non riser-pattern group. Kidney survival rates were significantly worse in the riser pattern group than in the non-riser-pattern group (p < 0.05). Moreover, among riser and non-riser pattern groups divided by BNP levels, the riser group with higher BNP level showed the worst kidney survival (p < 0.05). CONCLUSION: The riser pattern is frequently associated with several conditions at higher risk for kidney survival. Patients with a rising pattern and higher BNP levels have a worse kidney prognosis. PMID- 27367454 TI - Enabling xylose utilization in Yarrowia lipolytica for lipid production. AB - The conversion of lignocellulosic sugars, in particular xylose, is important for sustainable fuels and chemicals production. While the oleaginous yeast Yarrowia lipolytica is a strong candidate for lipid production, it is currently unable to effectively utilize xylose. By introducing a heterologous oxidoreductase pathway and enabling starvation adaptation, we obtained a Y. lipolytica strain, E26 XUS, that can use xylose as a sole carbon source and produce over 15 g/L of lipid in bioreactor fermentations (29.3% of theoretical yield) with a maximal lipid productivity of 0.19 g/L/h. Genomic sequencing and genetic analysis pointed toward increases in genomic copy number of the pathway and resulting elevated expression levels as the causative mutations underlying this improved phenotype. More broadly, many regions of the genome were duplicated during starvation of Yarrowia. This strain can form the basis for further engineering to enhance xylose catabolic rates and conversion. Finally, this study also reveals the flexibility and dynamic nature of the Y. lipolytica genome, and the means at which starvation can be used to induce genomic duplications. PMID- 27367453 TI - Ibrutinib Dosing Strategies Based on Interaction Potential of CYP3A4 Perpetrators Using Physiologically Based Pharmacokinetic Modeling. AB - Based on ibrutinib pharmacokinetics and potential sensitivity towards CYP3A4 mediated drug-drug interactions (DDIs), a physiologically based pharmacokinetic approach was developed to mechanistically describe DDI with various CYP3A4 perpetrators in healthy men under fasting conditions. These models were verified using clinical data for ketoconazole (strong CYP3A4 inhibitor) and used to prospectively predict and confirm the inducing effect of rifampin (strong CYP3A4 inducer); DDIs with mild (fluvoxamine, azithromycin) and moderate inhibitors (diltiazem, voriconazole, clarithromycin, itraconazole, erythromycin), and moderate (efavirenz) and strong CYP3A4 inducers (carbamazepine), were also predicted. Ketoconazole increased ibrutinib area under the curve (AUC) by 24 fold, while rifampin decreased ibrutinib AUC by 10-fold; coadministration of ibrutinib with strong inhibitors or inducers should be avoided. The ibrutinib dose should be reduced to 140 mg (quarter of maximal prescribed dose) when coadministered with moderate CYP3A4 inhibitors so that exposures remain within observed ranges at therapeutic doses. Thus, dose recommendations for CYP3A4 perpetrator use during ibrutinib treatment were developed and approved for labeling. PMID- 27367455 TI - Ammonium Additives to Dissolve Lithium Sulfide through Hydrogen Binding for High Energy Lithium-Sulfur Batteries. AB - In rechargeable Li-S batteries, the uncontrollable passivation of electrodes by highly insulating Li2S limits sulfur utilization, increases polarization, and decreases cycling stability. Dissolving Li2S in organic electrolyte is a facile solution to maintain the active reaction interface between electrolyte and sulfur cathode, and thus address the above issues. Herein, ammonium salts are demonstrated as effective additives to promote the dissolution of Li2S to 1.25 M in DMSO solvent at room temperature. NMR measurements show that the strong hydrogen binding effect of N-H groups plays a critical role in dissolving Li2S by forming complex ligands with S2- anions coupled with the solvent's solvating surrounding. Ammonium additives in electrolyte can also significantly improve the oxidation kinetics of Li2S, and therefore enable the direct use of Li2S as cathode material in Li-S battery system in the future. This provides a new approach to manage the solubility of lithium sulfides through cation coordination with sulfide anion. PMID- 27367456 TI - Synthesis, spectral characterization, DNA interaction, anticancer and molecular docking studies on some transition metal complexes with bidentate ligand. AB - The ligand, N(2),N(3)-bis(3-nitrophenyl)quinoxaline-2.3-diamine was prepared by the condensation of quinoxaline-2.3(1,4H)-dione with 3-nitroaniline. It was treated with Co(II), Ni(II), Cu(II) and Zn(II) acetates to form the metal complexes. These were characterized by elemental analysis, molar conductance, magnetic moment, UV-Vis., IR, (1)H NMR, ESR and mass spectral data. Octahedral geometry has been assigned to Co(II), Ni(II) and Zn(II) complexes, whereas Cu(II) complex has distorted octahedral geometry. From the powder XRD data, crystallite size and unit cell parameters were calculated. The surface morphology of the synthesized compounds were determined using SEM analysis. The antimicrobial activity of the compounds against some bacterial species viz. Escherichiacoli, Klebsiella pneumoniae, Pseudomonas aeuruginosa and Staphylococcus aureus; also the fungal species, Aspergillus niger, and Candida albicans were done by disc diffusion method. DNA binding, cleavage and super oxide anion scavenging activities were also evaluated. The DNA binding activity of the compounds were identified using electronic absorption titrations and DNA cleavage was determined using gel electrophoresis. The anticancer activities of the compounds against HeLa cell line were determined using MTT assay. The highly potent compound among the five against HeLa cell line is subjected to molecular docking study against human papilloma virus receptor molecule and ATP binding site of telomerase. PMID- 27367458 TI - To Appear in CHEMICAL REVIEWS, Vol. 99, No. 6, or in a later issue. PMID- 27367457 TI - Family Assessment of Quality of Care in the Last Month of Life. PMID- 27367459 TI - A new biarticular actuator design facilitates control of leg function in BioBiped3. AB - Bioinspired legged locomotion comprises different aspects, such as (i) benefiting from reduced complexity control approaches as observed in humans/animals, (ii) combining embodiment with the controllers and (iii) reflecting neural control mechanisms. One of the most important lessons learned from nature is the significant role of compliance in simplifying control, enhancing energy efficiency and robustness against perturbations for legged locomotion. In this research, we investigate how body morphology in combination with actuator design may facilitate motor control of leg function. Inspired by the human leg muscular system, we show that biarticular muscles have a key role in balancing the upper body, joint coordination and swing leg control. Appropriate adjustment of biarticular spring rest length and stiffness can simplify the control and also reduce energy consumption. In order to test these findings, the BioBiped3 robot was developed as a new version of BioBiped series of biologically inspired, compliant musculoskeletal robots. In this robot, three-segmented legs actuated by mono- and biarticular series elastic actuators mimic the nine major human leg muscle groups. With the new biarticular actuators in BioBiped3, novel simplified control concepts for postural balance and for joint coordination in rebounding movements (drop jumps) were demonstrated and approved. PMID- 27367460 TI - Effect of Dietary-Resistant Starch on Inhibition of Colonic Preneoplasia and Wnt Signaling in Azoxymethane-Induced Rodent Models. AB - Dietary fiber has been reported to prevent preneoplastic colon lesions. The aim of this study was to determine the effect of resistant starches, novel dietary fibers, on the development of colonic preneoplasia and Wnt signaling in azoxymethane (AOM)-treated rats and mice fed resistant starches at 55% of the diet after AOM treatment. Another objective was to determine the effect of resistant starches on the development of preneoplasia in rats treated with antibiotics (Ab), administered between AOM treatment and resistant starch feeding. Diets containing resistant starches, high-amylose (HA7), high-amylose octenyl succinic anhydride (OS-HA7), or high-amylose-stearic acid (SA-HA7) were compared with control cornstarch (CS). The resistant starch content of the diets did not alter the yield of colonic lesions but animals treated with AOM and fed the diet with the highest resistant starch content, SA-HA7 developed the highest average aberrant crypt foci (ACF) per animal. Mice fed the OS-HA7 diet had decreased expression of some upstream Wnt genes in the colonic crypts. This study suggests that further research is needed to determine if resistant starch impacts colon carcinogenesis in rodents. PMID- 27367462 TI - Perspectives on Neuroscience and Behavior. PMID- 27367461 TI - A safety evaluation of omacetaxine mepesuccinate for the treatment of chronic myeloid leukemia. AB - INTRODUCTION: Therapy of chronic myeloid leukemia (CML) has been completely transformed by the development of tyrosine kinase inhibitors (TKIs). However, a subset of patients will fail TKI therapy due to resistance or intolerance. Omacetaxine mepesuccinate (OM), a protein translation inhibitor, is currently the only approved therapy that does not directly target the kinase domain. It has activity for CML patients irrespective of the phase or underlying kinase domain mutation status. AREAS COVERED: We searched the MEDLINE database for articles published in English on homoharringtonine or omacetaxine from 1970 to present. This article reviews the pharmacokinetics of OM and its clinical evolution for the treatment of CML pre- and post TKI development. Toxicity profile, drug administration and future directions are also discussed. EXPERT OPINION: OM represents a unique addition to the CML therapeutic armamentarium with its distinct mechanism of action and activity. The adverse event profile is manageable and with subcutaneous administration at the approved dose, cardiac toxicity is no longer a concern. The recent approval of home administration will facilitate access to this therapy and increase patient compliance. We conclude with specific scenarios where OM use should be considered in CP and AP-CML patients in the era of TKI therapy. PMID- 27367463 TI - The Team Approach to Advanced Cancer Care-Redefining the Gold Standard. PMID- 27367465 TI - Pubic Hair Grooming Prevalence and Motivation Among Women in the United States. AB - Importance: Pubic hair grooming is an increasingly prevalent trend. Several studies have sought to characterize its prevalence, associated demographics, and motivations. Objective: To characterize current pubic hair grooming practices in the United States. Design, Setting, and Participants: In this cross-sectional study, a nationally representative survey was conducted in January 2013 of noninstitutionalized adults aged 18 to 65 years residing in the United States via the GfK Group (formerly Knowledge Networks) panel members. Data analysis was performed from November to December 2015. Interventions: A questionnaire examining pubic hair grooming habits. Main Outcomes and Measures: Demographic characteristics and motivations associated with pubic hair grooming. Results: A total of 3372 women were surveyed. Fifty-six women did not answer the grooming question; consequently, 3316 women were included in the analysis. Of these women, 2778 (83.8%) reported pubic hair grooming and 538 (16.2%) reported never grooming. On multivariate regression, several factors associated with grooming were found. When compared with younger women (aged 18-24 years), women aged 45 through 55 years (odds ratio [OR], 0.05; 95% CI, 0.01-0.49; P = .01) and those older than 55 years (OR, 0.04; 95% CI, 0.00-0.34; P = .003) were significantly less likely to groom. Women with some college (OR, 3.36; 95% CI, 1.65-6.84; P = .001) or a bachelor's degree (OR, 2.39; 95% CI, 1.17-4.88; P = .02) were more likely to have groomed. Race was also significantly associated with grooming, with all groups reporting less grooming when compared with white women. No association was found between grooming and income, relationship status, or geographic location. Conclusions and Relevance: This study provides a nationally representative assessment of contemporary female pubic hair grooming habits. Demographic differences in grooming were found, which may reflect cultural variations in preference related to pubic hair. Health care professionals and those who provide grooming services can use this information to better counsel patients and understand grooming practices. PMID- 27367466 TI - Inactivation and Environmental Stability of Zika Virus. PMID- 27367467 TI - Assessment of Solvated Interaction Energy Function for Ranking Antibody-Antigen Binding Affinities. AB - Affinity modulation of antibodies and antibody fragments of therapeutic value is often required in order to improve their clinical efficacies. Virtual affinity maturation has the potential to quickly focus on the critical hotspot residues without the combinatorial explosion problem of conventional display and library approaches. However, this requires a binding affinity scoring function that is capable of ranking single-point mutations of a starting antibody. We focus here on assessing the solvated interaction energy (SIE) function that was originally developed for and is widely applied to scoring of protein-ligand binding affinities. To this end, we assembled a structure-function data set called Single Point Mutant Antibody Binding (SiPMAB) comprising several antibody-antigen systems suitable for this assessment, i.e., based on high-resolution crystal structures for the parent antibodies and coupled with high-quality binding affinity measurements for sets of single-point antibody mutants in each system. Using this data set, we tested the SIE function with several mutation protocols based on the popular methods SCWRL, Rosetta, and FoldX. We found that the SIE function coupled with a protocol limited to sampling only the mutated side chain can reasonably predict relative binding affinities with a Spearman rank-order correlation coefficient of about 0.6, outperforming more aggressive sampling protocols. Importantly, this performance is maintained for each of the seven system-specific component subsets as well as for other relevant subsets including non-alanine and charge-altering mutations. The transferability and enrichment in affinity-improving mutants can be further enhanced using consensus ranking over multiple methods, including the SIE, Talaris, and FOLDEF energy functions. The knowledge gained from this study can lead to successful prospective applications of virtual affinity maturation. PMID- 27367468 TI - Cardiac background sodium current: Elusive but important. PMID- 27367470 TI - Schrodinger's Cat and d-Cycloserine to Augment Exposure Therapy-Both Are Alive and Dead. PMID- 27367469 TI - Primary Gleason pattern upgrading in contemporary patients with D'Amico low-risk prostate cancer: implications for future biomarkers and imaging modalities. AB - OBJECTIVE: To retrospectively assess the rate of high-grade primary Gleason upgrading (HGPGU) to primary Gleason pattern 4 or 5 in a contemporary cohort of patients with D'Amico low-risk prostate cancer including those who fulfilled Prostate Cancer Research International Active Surveillance (PRIAS) criteria, and to develop a tool for HGPGU prediction. HGPGU is a contraindication in most active surveillance (AS) and focal therapy protocols. PATIENTS AND METHODS: In all, 10 616 patients with localised prostate cancer were treated at a high-volume European tertiary care centre from 2010 to 2015 with radical prostatectomy. Analyses were restricted to 1 819 patients with D'Amico low-risk prostate cancer (17.1%) with prostate-specific antigen (PSA) levels of <10.0 ng/mL, cT1c-cT2a and Gleason score <=6, and were repeated within 772 of the men (7.3%) who fulfilled the PRIAS criteria for AS (PSA level of <=10 ng/mL, T1c-T2, Gleason score <=6, PSA density (PSAD) of <0.2 ng/mL2 , <=2 positive cores). Uni- and multivariable logistic regression models were fitted, testing predictors of HGPGU. The final logistic regression model was based on the most informative variables. RESULTS: There was HGPGU in 88 (4.8%) patients with D'Amico low-risk prostate cancer and in 32 (4.1%) of the subgroup who were PRIAS eligible. Multivariable analysis predicting HGPGU for the patients with D'Amico low-risk yielded three independent predictors: age, PSAD, and clinical tumour stage (P = 0.008, P = 0.005 and P = 0.021, respectively). Within the same patients, the model using all vs the most informative variables resulted in area under the curves (AUCs) of 69.2% and 68.3%, respectively. Multivariable analysis of those who were PRIAS eligible, yielded age and number of positive cores as independent predictors of HGPGU (P = 0.002 and P = 0.049, respectively; AUC 64.9%). CONCLUSIONS: The low accuracy (invariably <70%) for HGPGU prediction in both patients with D'Amico low-risk prostate cancer and PRIAS eligibility indicates that these variables have poor predictive ability in contemporary patients. Despite HGPGU being a rare phenomenon, it may have life threatening implications and consequently alternatives such as biomarkers, genetic markers, or imaging modalities at re biopsy are needed. PMID- 27367471 TI - Late Persistent Positive EBV Viral Load and Risk of Solid Cancer in Kidney Transplant Patients. AB - BACKGROUND: Recent studies reported that posttransplant Epstein-Barr virus (EBV) replication is frequent and indicates overimmunosuppression. We hypothesized that long-term EBV replication may identify overimmunosuppressed patients at higher risk of cancer. METHODS: We analyzed a prospective cohort of renal transplant recipients having routine EBV PCR surveillance. All cancers (except EBV-related neoplasia) were recorded. RESULTS: Mean follow up was 94 + 23 months. Samples (8412) were available in 669 patients. Three hundred eighty-eight of the 669 patients (58%) had at least 1 positive viremia during follow-up.Epstein-Barr virus D+/R- patients (P = 0.046) as well as those having received antithymocyte globulin (P < 0.001) were more likely to develop persistent EBV viremia. Eighty six patients (12.9%) developed a cancer during follow-up. The cumulated incidence of cancer was higher in patients with persistent high EBV replication (22.4% vs 10.2%, P = 0.005). The effect of persistent EBV infection remained significant even after adjustment for all confounding factors (hazard ratio, 1.69; 95% confidence interval, 1.10-2.61; P = 0.018). Age, history of antithymocyte globulin use, smoking, and history of cancer were also associated with cancer occurrence. CONCLUSIONS: Persistent high EBV viral load is associated with the occurrence of solid cancer. In this setting, more intensive screening and/or minimization of immunosuppressive treatment are probably required. PMID- 27367472 TI - A Difficult Decision: Atypical JC Polyomavirus Encephalopathy in a Kidney Transplant Recipient. AB - BACKGROUND: A number of cerebral manifestations are associated with JC polyomavirus (JCPyV) which are diagnosed by detection of JCPyV in cerebrospinal fluid (CSF), often with the support of cerebral imaging. Here we present an unusual case of a kidney transplant patient presenting with progressive neurological deterioration attributed to JCPyV encephalopathy. METHODS: Quantitative polymerase chain reaction JCPyV was used prospectively and retrospectively to track the viral load within the patient blood, urine, CSF, and kidney sections. A JCPyV VP1 enzyme-linked immunosorbent assay was used to measure patient and donor antibody titers. Immunohistochemical staining was used to identify active JCPyV infection within the kidney allograft. RESULTS: JC polyomavirus was detected in the CSF at the time of presentation. JC polyomavirus was not detected in pretransplant serum, however viral loads increased with time, peaking during the height of the neurological symptoms (1.5E copies/mL). No parenchymal brain lesions were evident on imaging, but transient cerebral venous sinus thrombosis was present. Progressive decline in neurological function necessitated immunotherapy cessation and allograft removal, which led to decreasing serum viral loads and resolution of neurological symptoms. JC polyomavirus was detected within the graft's collecting duct cells using quantitative polymerase chain reaction and immunohistochemical staining. The patient was JCPyV naive pretransplant, but showed high antibody titers during the neurological symptoms, with the IgM decrease paralleling the viral load after graft removal. CONCLUSIONS: We report a case of atypical JCPyV encephalopathy associated with cerebral venous sinus thrombosis and disseminated primary JCPyV infection originating from the kidney allograft. Clinical improvement followed removal of the allograft and cessation of immunosuppression. PMID- 27367473 TI - Randomized Controlled Trial of a Computer-Based Education Program in the Home for Solid Organ Transplant Recipients: Impact on Medication Knowledge, Satisfaction, and Adherence. AB - BACKGROUND: De novo solid organ transplant recipients (SOTR) have a steep learning curve to acquire medication knowledge. Without adequate knowledge, SOTR are at risk of nonadherence and poor transplant outcomes. METHODS: In this nonblinded, randomized controlled trial, de novo SOTR received standard teaching with or without postdischarge computer-based education (CBE) at home. Primary outcomes were change in knowledge (quiz and recall) and satisfaction, assessed by questionnaires at baseline and 3 months. Adherence was evaluated via self-report and immunosuppressant levels. RESULTS: Two hundred forty-six patients were randomized and 209 completed the 3-month analysis. In the intervention arm, 73 (57.9%) used the CBE program. Change in knowledge quiz score did not differ between groups (4.9% vs 0.6%; P = 0.084), despite a significant increase within the intervention (72.4% vs 77.3%, P = 0.007) but not the control (76.0% vs 76.6%, P = 0.726) arms. Both groups had a significant improvement in recall (intervention, 56.7% vs 82.1%, P < 0.001; control, 51.3% vs 79.7%, P < 0.001), with similar changes in scores (25.4% vs 28.4%, P = 0.55). Change in satisfaction differed between groups (intervention, 1.2% vs control, -4.9%; P = 0.050). There was a significant decline in satisfaction within the control group (88.4% vs 83.5%, P = 0.035), whereas satisfaction was maintained with the intervention (85.6% vs 86.8%, P = 0.55). Adherence was similar in both groups. CONCLUSIONS: Knowledge improved over the study period in both groups, with no incremental benefit for the intervention. Patient satisfaction was maintained with the CBE program. More research is needed to identify barriers to uptake of CBE at home and to develop effective strategies for posttransplant education. PMID- 27367474 TI - Simple markers can distinguish Takotsubo cardiomyopathy from ST segment elevation myocardial infarction. AB - BACKGROUND: Takotsubo cardiomyopathy (TTC) is a clinical condition mimicking acute myocardial infarction. A specific biomarker for TTC screening is required, but until now, no single biomarker has been established for the early diagnosis of TTC and differentiation from ST-segment elevation myocardial infarction (STEMI). In our study we focused on the simple markers that are available in every hospital. METHODS: In 66 consecutive patients (pts) who were hospitalized with TTC and 66 pts with STEMI, cardiac biomarkers, such as NT-proBNP, TnI, CK and CKMB mass were determined during 12h from admission and compared with demographic, clinical and echocardiographic findings. RESULTS: The concentration of NTproBNP was greater in pts with TTC than STEMI (4702pg/ml vs 2138pg/ml). The concentration of TnI and CKMB mass was greater in the STEMI group than in the TTC group (TnI: 2.1ng/ml and CK MB mass: 9.5ng/ml in pts with TTC vs TnI: 19ng/ml and CK MB mass: 73.3ng/ml in pts with STEMI). The NTproBNP/TnI ratio and NTproBNP/CKMB mass ratio were, respectively, 2235.2 and 678.2 in pts with TTC and 81.6 and 27.5 in pts with STEMI (p<0.001). Moreover, the NTproBNP/EF ratio was also statistically significant (110.4 in TTC group and 39.4 in STEMI group). CONCLUSIONS: NTproBNP/TnI, NTproBNP/CKMB mass and NTproBNP/EF ratios can distinguish TTC from STEMI at an early stadium. The most accurate marker is the NTproBNP/TnI ratio. PMID- 27367475 TI - Complex band structures of transition metal dichalcogenide monolayers with spin orbit coupling effects. AB - Recently, the transition metal dichalcogenides have attracted renewed attention due to the potential use of their low-dimensional forms in both nano- and opto electronics. In such applications, the electronic and transport properties of monolayer transition metal dichalcogenides play a pivotal role. The present paper provides a new insight into these essential properties by studying the complex band structures of popular transition metal dichalcogenide monolayers (MX 2, where M = Mo, W; X = S, Se, Te) while including spin-orbit coupling effects. The conducted symmetry-based tight-binding calculations show that the analytical continuation from the real band structures to the complex momentum space leads to nonlinear generalized eigenvalue problems. Herein an efficient method for solving such a class of nonlinear problems is presented and yields a complete set of physically relevant eigenvalues. Solutions obtained by this method are characterized and classified into propagating and evanescent states, where the latter states manifest not only monotonic but also oscillatory decay character. It is observed that some of the oscillatory evanescent states create characteristic complex loops at the direct band gap of MX 2 monolayers, where electrons can directly tunnel between the band gap edges. To describe these tunneling currents, decay behavior of electronic states in the forbidden energy region is elucidated and their importance within the ballistic transport regime is briefly discussed. PMID- 27367476 TI - Terahertz Conductivity within Colloidal CsPbBr3 Perovskite Nanocrystals: Remarkably High Carrier Mobilities and Large Diffusion Lengths. AB - Colloidal CsPbBr3 perovskite nanocrystals (NCs) have emerged as an excellent light emitting material in last one year. Using time domain and time-resolved THz spectroscopy and density functional theory based calculations, we establish 3 fold free carrier recombination mechanism, namely, nonradiative Auger, bimolecular electron-hole recombination, and inefficient trap-assisted recombination in 11 nm sized colloidal CsPbBr3 NCs. Our results confirm a negligible influence of surface defects in trapping charge carriers, which in turn results into desirable intrinsic transport properties, from the perspective of device applications, such as remarkably high carrier mobility (~4500 cm(2) V( 1) s(-1)), large diffusion length (>9.2 MUm), and high luminescence quantum yield (80%). Despite being solution processed and possessing a large surface to volume ratio, this combination of high carrier mobility and diffusion length, along with nearly ideal photoluminescence quantum yield, is unique compared to any other colloidal quantum dot system. PMID- 27367477 TI - Double IGHV DNA gene rearrangements in CLL: influence of mixed-mutated and unmutated rearrangements on outcomes in CLL. PMID- 27367479 TI - Corrigendum. PMID- 27367480 TI - Evaluation of the prognostic value of electrocardiography parameters and heart rhythm in patients with pulmonary hypertension. AB - BACKGROUND: Several studies have analyzed arrhythmias in patients with pulmonary hypertension (PH) and increased P-wave duration was identified as a risk factor for development of atrial fibrillation (AF). METHODS: We retrospectively analyzed the incidence of arrhythmias in patients with an initial diagnosis of PH during long-term follow-up and assessed the prognostic value of electrocardiography (ECG) data. Data from 167 patients were analyzed (Dana Point Classification: Group 1: 59 patients, Group 2: 28 patients, Group 3: 39 patients, Group 4: 41 patients). Clinical, 6-min-ute walk distance test, echocardiography and right heart catheterization data were collected, and baseline/follow-up ECGs were analyzed. RESULTS: Baseline ECGs revealed sinus rhythm in 137 patients. Thirteen patients had newly onset AF during follow-up. In 30 patients, baseline ECG showed AF. Patients with baseline AF showed higher atrial diameters and higher right atrial pressure. Patients with P-wave du-ration > 0.11 s had shorter survival. Other ECG parameters (PQ-interval, QRS-width, QT-/ /QTc-interval) were not associated with survival. Mean survival times were 79.4 +/- 5.4 months (sinus rhythm), 64.4 +/- 12.9 months (baseline AF) and 58.8 +/- 8.9 months (newly onset AF during follow-up) (p = 0.565). CONCLUSIONS: Atrial fibrillation predict adverse prognosis in patients with PH and a longer P-wave (> 0.11 s) is associated with shorter survival time. PMID- 27367478 TI - 'Acute myeloid leukemia: a comprehensive review and 2016 update'. AB - Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with an incidence of over 20 000 cases per year in the United States alone. Large chromosomal translocations as well as mutations in the genes involved in hematopoietic proliferation and differentiation result in the accumulation of poorly differentiated myeloid cells. AML is a highly heterogeneous disease; although cases can be stratified into favorable, intermediate and adverse-risk groups based on their cytogenetic profile, prognosis within these categories varies widely. The identification of recurrent genetic mutations, such as FLT3 ITD, NMP1 and CEBPA, has helped refine individual prognosis and guide management. Despite advances in supportive care, the backbone of therapy remains a combination of cytarabine- and anthracycline-based regimens with allogeneic stem cell transplantation for eligible candidates. Elderly patients are often unable to tolerate such regimens, and carry a particularly poor prognosis. Here, we review the major recent advances in the treatment of AML. PMID- 27367481 TI - Decreased carotid and vertebral arterial blood-flow velocity in response to orthostatic unload in patients with severe aortic stenosis. AB - BACKGROUND: Responses of cerebral blood flow to the postural unloading maneuver in aortic stenosis (AS) have not been described so far. Our aim was to assess effects of orthostatic stress test on changes of carotid and vertebral artery blood flow and transaortic gradients. METHODS: From consecutive 101 AS patients we selected 50 patients with severe isolated AS. Maximal and mean transaortic pressure gradients, as well as peak systolic blood-flow velocity (PSV) and end diastolic velocity (EDV) in the common carotid artery, internal carotid artery and vertebral artery on both sides were measured by duplex ultrasound in the supine position and at 1-2 min after the assumption of the sitting position in patients with AS, and in stand-ing position in healthy controls. RESULTS: The orthostatic stress test induced significant decrease of carotid and vertebral arterial flow velocities in AS patients. Transaortic pressure gradients also dropped while the patients were sitting (p < 0.001). A history of syncope/presyncope was not associated with a significantly lower PSV and EDV in carotid and vertebral arteries in the upright position. In healthy controls, the velocities in carotid and vertebral arterial flow have been unchanged after maneuver reducing preload. CONCLUSIONS: In AS patients, decrease of carotid and vertebral arterial flow velocities and transaortic gradients in the sitting position were observed. Orthostatic test position does not ap-pear to be associated with a history of syncope/presyncope in patients with severe isolated AS, de-spite a simultaneous drop of transvalvular pressure gradient. PMID- 27367483 TI - Health Care for Lesbian, Gay, and Bisexual People Comes Out of the Closet. PMID- 27367482 TI - Impact of age on adjuvant chemotherapy after radical resection in patients with non-small cell lung cancer. AB - Adjuvant chemotherapy (ACT) after radical surgery is known to improve the survival of patients with non-small cell lung cancer (NSCLC). However, there are few studies reporting the impact of age on the efficacy of ACT in NSCLC patients. All patients who received postoperative ACT in the Cancer Hospital, the Chinese Academy of Medical Sciences, between 2001 and 2013 with complete records in the database of the hospital and met the inclusion criteria were enrolled in this study for analysis. The primary end point was disease-free survival (DFS) in terms of age. Survival analysis was performed using Kaplan-Meier estimates, log rank tests, and Cox's proportional hazards regression analysis. Propensity score matching (PSM) was used, survival analysis and subgroup analysis of the match data were carried out. Of 1095 patients with stage IB to stage IIIA NSCLC who underwent radical resection, 865 cases who met the inclusion criteria were analyzed. Of them, 156 (18.0%) patients were 65 years old or older, and the remaining 709 (82.0%) patients were younger than 65. The DFS between the younger group and the elderly group was not significantly different neither before PSM (100.714 weeks [95% CI: 84.421, 117.007] vs. 99.571 weeks [95% CI: 82.621, 116.522]; P = 0.555) nor after PSM (104.857 weeks [95% CI: 81.495, 128.220] vs. 97.429 weeks [95% CI: 81.743, 113.114]; P = 0.328) using the Kaplan-Meier method.The results suggest that the benefit on DFS was similar regardless of age of NSCLC patients. ACT should not be withheld from elderly patients. However, these conclusions are limited by the nature of this retrospective study, and therefore prospective trials are required for further verification. PMID- 27367484 TI - Severe Maternal Morbidity and Postpartum Depressive Symptomatology: A Prospective Double Cohort Comparison Study. AB - The adverse consequences to mothers of postpartum depression are well-documented, and risk factors are of interest. There is limited evidence on postpartum depression among women with severe maternal morbidity, defined as potentially life-threatening conditions during pregnancy, childbirth, or soon after termination of pregnancy. We compared postpartum depressive symptoms of postpartum women aged 18 and older who delivered in two tertiary referral hospitals in 2014 in Kelantan, Malaysia, and had (n = 145) or had not (n = 187) suffered severe maternal morbidity. A prospective double cohort study design was applied. Postpartum depressive symptoms were assessed at 1 and 6 months postpartum using the Malay version of the Edinburgh Postnatal Depression Scale. There was no significant difference in the mean Edinburgh Postnatal Depression Scale score changes (p = .803) between the two groups of women, after adjusting for age, social support, physical health, occupation, and education. Factors other than severe medical complications should be pursued as predictors of postpartum depressive symptomatology. (c) 2016 Wiley Periodicals, Inc. PMID- 27367485 TI - Coenzyme Q10 as a Peripheral Biomarker for Multiple System Atrophy. PMID- 27367486 TI - Somatic syndromes and chronic pain in women with overactive bladder. AB - AIMS: Mechanisms underlying pain perception and afferent hypersensitivity, such as central sensitization, may impact overactive bladder (OAB) symptoms. However, little is known about associations between OAB symptom severity, pain experience, and presence of comorbid chronic pain syndromes. This study examined relationships between OAB symptoms, somatic symptoms, and specific chronic pain conditions in which central sensitization is believed to play a primary role, in a community-based sample of adult women with OAB. METHODS: We recruited adult women with OAB to complete questionnaires assessing urinary symptoms, pain and somatic symptoms, and preexisting diagnoses of central sensitivity syndromes. We analyzed the effects of overall bodily pain intensity, general somatic symptoms, and diagnoses of central sensitivity syndromes on OAB symptom bother and health related quality of life. RESULTS: Of the 116 women in this study, over half (54%) stated their urge to urinate was associated with pain, pressure, or discomfort. Participants reported a wide range of OAB symptoms and health-related quality of life. There was a significant, positive correlation between OAB symptoms and somatic symptoms as well as overall pain intensity. Only 7% of women met diagnostic criteria for fibromyalgia; yet these women demonstrated significantly increased OAB symptom burden and decreased OAB quality of life compared to those without fibromyalgia. CONCLUSION: Women with more severe OAB symptoms reported increased general somatic symptom burden and increased overall body pain intensity, especially women with fibromyalgia. These findings suggest that attributes of pain and co-morbidity with chronic pain conditions may impact the experience of OAB symptoms for many women. Neurourol. Urodynam. 36:1113-1118, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27367487 TI - Changing HIV treatment eligibility under health system constraints in sub-Saharan Africa: investment needs, population health gains, and cost-effectiveness. AB - OBJECTIVE: We estimated the investment needs, population health gains, and cost effectiveness of different policy options for scaling-up prevention and treatment of HIV in the 10 countries that currently comprise 80% of all people living with HIV in sub-Saharan Africa (Ethiopia, Kenya, Malawi, Mozambique, Nigeria, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe). DESIGN: We adapted the established STDSIM model to capture the health system dynamics: demand-side and supply-side constraints in the delivery of antiretroviral treatment (ART). METHODS: We compared different scenarios of supply-side (i.e. health system capacity) and demand-side (i.e. health seeking behavior) constraints, and determined the impact of changing guidelines to ART eligibility at any CD4 cell count within these constraints. RESULTS: Continuing current scale-up would require US$178 billion by 2050. Changing guidelines to ART at any CD4 cell count is cost-effective under all constraints tested in the model, especially in demand side constrained health systems because earlier initiation prevents loss-to follow-up of patients not yet eligible. Changing guidelines under current demand side constraints would avert 1.8 million infections at US$208 per life-year saved. CONCLUSION: Treatment eligibility at any CD4 cell count would be cost effective, even under health system constraints. Excessive loss-to-follow-up and mortality in patients not eligible for treatment can be avoided by changing guidelines in demand-side constrained systems. The financial obligation for sustaining the AIDS response in sub-Saharan Africa over the next 35 years is substantial and requires strong, long-term commitment of policy-makers and donors to continue to allocate substantial parts of their budgets. PMID- 27367488 TI - The M184I/V and K65R nucleoside resistance mutations in HIV-1 prevent the emergence of resistance mutations against dolutegravir. AB - OBJECTIVE: Recommended treatments for newly diagnosed HIV-positive individuals now focus on the integrase strand transfer inhibitors, raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG). In treatment-naive individuals, cases of RAL-based and EVG-based virological failure, although rare, are associated with the occurrence of resistance mutations in integrase and/or reverse transcriptase coding sequences. In such cases, common resistance substitutions in reverse transcriptase that were associated with nucleos(t)ide reverse transcriptase inhibitors included M184I/V and K65R and these occurred together with various mutations in integrase. In some instances, these mutations in reverse transcriptase preceded the emergence of mutations in integrase. In contrast, no resistance substitutions in either integrase or reverse transcriptase have been observed to date in viruses isolated from treatment-naive individuals who experienced treatment failure with DTG-based regimens. DESIGN: The objective of this study was to determine the effects of the M184I/V and K65R substitutions in reverse transcriptase on the ability of HIV-1 to become resistant against RAL, EVG or DTG. METHODS: We performed tissue culture selection experiments using reverse transcriptase inhibitor-resistant viruses containing resistance substitutions at positions K65R, M184I or M184V in the presence of increasing concentrations of RAL, EVG or DTG and monitored changes in integrase sequences by genotyping. RESULTS: Selections using EVG and RAL led to the emergence of resistance mutations in integrase. In contrast, only the wild-type virus was able to acquire resistance mutations for DTG. CONCLUSION: Resistance mutations against nucleos(t)ide reverse transcriptase inhibitors antagonized the development of HIV-1 resistance against DTG but not RAL or EVG. PMID- 27367489 TI - Population health and individualized care in the global AIDS response: synergy or conflict? PMID- 27367490 TI - Folate and MMA predict cognitive impairment in elderly stroke survivors: A cross sectional study. AB - Elderly stroke survivors are at risk of malnutrition and long-term cognitive impairment. Vitamin B-related metabolites, folate and methylmalonic acid, have been implicated in cognitive function. We conducted a study exploring the relationship between blood folate, methylmalonic acid and post-stroke cognitive impairment. This is a cross sectional study of elderly Swedish patients (n=149) 20 months post-stroke, assessed using the Mini Mental State Examination, serum blood levels of methylmalonic acid and red blood cell levels of folate. Linear modeling indicated that low levels of blood folate and elevated methylmalonic acid significantly contributed to cognitive impairment in stroke survivors. Half of the stroke survivors were shown to have folate deficiency at 20 months after stroke. Folate deficiency is common long term after stroke and both low folate and elevated methylmalonic acid appear to be associated with long term cognitive impairment, in elderly Swedish stroke survivors. PMID- 27367491 TI - Motivational factors and negative affectivity as predictors of alcohol craving. AB - Craving is thought to play an important role in alcohol use disorders. The recent inclusion of "craving" as a formal diagnostic symptom calls for further investigation of this subjective phenomenon with multiple dimensions. Considering that alcohol-dependent patients compensate negative physical/emotional states with alcohol, the aim of this study is to investigate alcohol craving and its correlation with drinking measures and affective personality dimensions. A sample of 135 alcohol-dependent patients (104 males and 31 females) was collected from a clinical setting. Subjects self-rated their cravings (Penn Alcohol Craving Scale) and the stage of change. Several personality scales were also administered. Craving was related to drinking status, abstinence time, age, and taking steps. After controlling for these conditions, psychological characteristics related to low self-concept, neuroticism, cyclothymic affective temperament, depression, and hostility were found to be predictors of craving in sober alcohol-dependent patients. Our results support craving as a component of the phenomenology of alcohol dependence and highlight the presence of unpleasant feelings as predictors of craving in sober alcohol-dependent patients without co-occurring psychiatric conditions. The predisposition to experience negative emotions may induce a stronger craving response and increase the likelihood of a first drink and a subsequent loss of control. PMID- 27367492 TI - Traditional Chinese version of the Mayer Salovey Caruso Emotional Intelligence Test (MSCEIT-TC): Its validation and application to schizophrenic individuals. AB - Schizophrenia is an illness that impairs a person's social cognition. The Mayer Salovey Caruso Emotional Intelligence Test (MSCEIT) is the most well-known test used to measure emotional intelligence (EI), which is a major component of social cognition. Given the absence of EI ability-based scales adapted to Chinese speakers, we translated the MSCEIT into a Traditional Chinese version (MSCEIT-TC) and validated this scale for use in schizophrenia studies. The specific aims were to validate the MSCEIT-TC, to develop a norm for the MSCEIT-TC, and use this norm to explore the EI performance of schizophrenic individuals. We included in our study seven hundred twenty-eight healthy controls and seventy-six individuals with schizophrenia. The results suggest that the MSCEIT-TC is reliable and valid when assessing EI. The results showed good discrimination and validity when comparing the two study groups. Impairment was the greatest for two branches Understanding and Managing Emotions, which implies that the deficits of schizophrenia individuals involve ToM (theory of mind) tasks. Deficits involving the negative scale of schizophrenia was related to impaired performance when the MSCEIT-TC was used (in branch 2, 3, 4, and the area Strategic). Our findings suggest that the MSCEIT-TC can be used for emotional studies in healthy Chinese and in clinical setting for investigating schizophrenic individuals. PMID- 27367494 TI - Chyme reinfusion or enteroclysis in nutrition of patients with temporary double enterostomy or enterocutaneous fistula. AB - PURPOSE OF REVIEW: Patients with double temporary enterostomy or enterocutaneous fistula may suffer from intestinal failure. Parenteral nutrition is the gold standard treatment until surgical re-establishment of intestinal continuity, but serious complications may arise. Chyme reinfusion or enteroclysis are indicated. RECENT FINDINGS: Chyme reinfusion corrects the intestinal failure by restoring intestinal absorption, allowing parenteral nutrition weaning in 91% of patients. Chyme reinfusion contributes to improve nutritional status and reduce plasma liver test abnormalities. Chyme reinfusion is feasible at home without any serious complications in selected patients. Mechanisms underlying chyme reinfusion effectiveness on intestinal function, such as restoration of ileal brake, are suggested but most remain to be demonstrated. When the downstream small bowel is exposed, enteroclysis of enteral nutrition or hydration could be helpful to reduce parenteral nutrition needs, or in case of insufficient food intake during chyme reinfusion. SUMMARY: Chyme reinfusion or enteroclysis are less expensive, well tolerated, and easy-to-use nutrition support techniques, which may allow reducing parenteral nutrition-related healthcare costs. The latter remains to be demonstrated in the setting of a prospective randomized controlled trial. This review may contribute to improve the awareness of intensivists, digestive surgeons, and gastroenterologists involved in intestinal failure management to spread the use of chyme reinfusion or enteroclysis. PMID- 27367493 TI - Cinnamoyloxy-mammeisin Isolated from Geopropolis Attenuates Inflammatory Process by Inhibiting Cytokine Production: Involvement of MAPK, AP-1, and NF-kappaB. AB - Chemical compounds belonging to the class of coumarins have promising anti inflammatory potential. Cinnamoyloxy-mammeisin (CNM) is a 4-phenylcoumarin that can be isolated from Brazilian geopropolis. To our knowledge, its anti inflammatory activity has never been studied. Therefore, the present study investigated the anti-inflammatory activity of CNM and elucidated its mechanism of action on isolated macrophages. Pretreatment with CNM reduced neutrophil migration into the peritoneal and joint cavity of mice. Likewise, CNM reduced the in vitro and in vivo release of TNF-alpha and CXCL2/MIP-2. Regarding the possible molecular mechanism of action, CNM reduced the phosphorylation of proteins ERK 1/2, JNK, p38 MAPK, and AP-1 (subunit c-jun) in PG-stimulated macrophages. Pretreatment with CNM also reduced NF-kappaB activation in RAW 264.7 macrophages stably expressing the NF-kappaB-luciferase reporter gene. On the other hand, it did not alter IkappaBalpha degradation or nuclear translocation of p65. Thus, the results of this study demonstrate promising anti-inflammatory activity of CNM and provide an explanation of its mechanism of action in macrophages via inhibition of MAPK signaling, AP-1, and NF-kappaB. PMID- 27367495 TI - Ophthalmic Complications Associated with Direct Oral Anticoagulant Medications. AB - OBJECTIVE: To describe the clinical features and management of six patients with ocular complications associated with direct oral anticoagulants (DOACs). METHODS: The medical records of all adult patients known to be taking a DOAC and with an unusual bleeding event at a large tertiary referral center over a one-year period were reviewed. Patients with less than one-month follow-up were excluded. Data collection included relevant clinic notes, operative reports, surgical videos, and clinical images (fundus photography, optical coherence tomography, B-scan ultrasonography, and fluorescein angiography). RESULTS: Six eyes in six patients were identified with an unusual bleeding event associated with DOAC use. One patient was taking apixaban, two patients were taking dabigatran, and three patients were taking rivaroxaban. Two patients had large submacular hemorrhage (including one with vitreous hemorrhage breakthrough), three patients had vitreous hemorrhage, and one patient had recurrent hyphema. Presenting visual acuity ranged from 20/40 to light perception. Three individuals required therapeutic and/or diagnostic pars plana vitrectomy for vitreous hemorrhage. Final visual acuity ranged from 20/25 to count finger vision. The associated DOAC was permanently discontinued in two of the six cases. Follow-up was one to four months from onset of identified DOAC-related complication. CONCLUSIONS: DOAC use may be associated with ocular bleeding. Ophthalmologists should be aware of potential hemorrhagic complications and obtain consultation with primary providers regarding DOAC cessation guidelines. PMID- 27367496 TI - Uterine Cancer After Risk-Reducing Salpingo-oophorectomy Without Hysterectomy in Women With BRCA Mutations. AB - Importance: The link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial. Objective: To determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy. Design, Setting, and Participants: This multicenter prospective cohort study included 1083 women with a deleterious BRCA1 or BRCA2 mutation identified from January 1, 1995, to December 31, 2011, at 9 academic medical centers in the United States and the United Kingdom who underwent RRSO without a prior or concomitant hysterectomy. Of these, 627 participants were BRCA1+; 453, BRCA2+; and 3, both. Participants were prospectively followed up for a median 5.1 (interquartile range [IQR], 3.0-8.4) years after ascertainment, BRCA testing, or RRSO (whichever occurred last). Follow up data available through October 14, 2014, were included in the analyses. Censoring occurred at uterine cancer diagnosis, hysterectomy, last follow-up, or death. New cancers were categorized by histologic subtype, and available tumors were analyzed for loss of the wild-type BRCA gene and/or protein expression. Main Outcomes and Measures: Incidence of uterine corpus cancer in BRCA+ women who underwent RRSO without hysterectomy compared with rates expected from the Surveillance, Epidemiology, and End Results database. Results: Among the 1083 women women who underwent RRSO without hysterectomy at a median age 45.6 (IQR: 40.9 - 52.5), 8 incident uterine cancers were observed (4.3 expected; observed to expected [O:E] ratio, 1.9; 95% CI, 0.8-3.7; P = .09). No increased risk for endometrioid endometrial carcinoma or sarcoma was found after stratifying by subtype. Five serous and/or serous-like (serous/serous-like) endometrial carcinomas were observed (4 BRCA1+ and 1 BRCA2+) 7.2 to 12.9 years after RRSO (BRCA1: 0.18 expected [O:E ratio, 22.2; 95% CI, 6.1 56.9; P < .001]; BRCA2: 0.16 expected [O:E ratio, 6.4; 95% CI, 0.2-35.5; P = .15]). Tumor analyses confirmed loss of the wild-type BRCA1 gene and/or protein expression in all 3 available serous/serous-like BRCA1+ tumors. Conclusions and Relevance: Although the overall risk for uterine cancer after RRSO was not increased, the risk for serous/serous-like endometrial carcinoma was increased in BRCA1+ women. This risk should be considered when discussing the advantages and risks of hysterectomy at the time of RRSO in BRCA1+ women. PMID- 27367498 TI - Multimodal Imaging of Reticular Pseudodrusen in a Population-Based Setting: The Alienor Study. AB - PURPOSE: To document reticular pseudodrusen (RPD) using multimodal imaging in French elderly subjects. METHODS: A total of 494 subjects (970 eyes) aged 77 years or more, from the Alienor study, were examined in 2011 and 2012. Reticular pseudodrusen were defined as definite if they were present with at least two imaging methods among color retinal photographs, macular cube (20 degrees * 15 degrees ) of spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and infrared reflectance (IR). The Youden index was calculated as specificity + sensitivity - 1. RESULTS: The prevalence of definite RPD was 13.4% and was higher among women (15.6%) than men (10.2%). It increased with age and reached almost 50% in subjects over 85 years. Infrared reflectance was the most sensitive technique (100%) and color fundus photography the least sensitive (34.5% at left eyes and 48.1% at right eyes). The best Youden index was obtained with IR (0.96 at both eyes) followed by SD-OCT (0.87 at right eye and 0.78 at left eye). Reticular pseudodrusen were present in 4.6% of eyes without AMD, 13.0% with early AMD1, 62.6% with early AMD2, 34.6% with atrophic AMD, and 8.1% with neovascular AMD. Reticular pseudodrusen were significantly associated with central and pericentral intermediate soft drusen (odds ratio [OR]: 2.14; 95% confidence interval [CI] = 1.11-4.14 and OR: 1.49; 95% CI = 1.16-1.90, respectively) and central large soft drusen (OR: 1.67; 95% CI = 1.16-2.42). CONCLUSIONS: Using multimodal imaging, the prevalence of RPD appears higher than previously reported in studies based on retinal photography only. Reticular pseudodrusen frequently accompany other signs of AMD. Infrared reflectance and SD OCT appear to be particularly relevant methods to diagnose RPD. PMID- 27367497 TI - RINT1 functions as a multitasking protein at the crossroads between genomic stability, ER homeostasis, and autophagy. AB - RINT1 was first identified as an RAD50-interacting protein and its function was therefore linked to the maintenance of genomic stability. It was also shown that RINT1 was a key player in ER-Golgi trafficking as a member of an ER tethering complex interacting with STX18. However, due to early embryonic lethality of rint1-null mice, the in vivo functions of RINT1 remained for the most part elusive. We recently described the consequences of Rint1 inactivation in various neuronal cells of the central nervous system. We observed that lack of RINT1 in vivo triggers genomic instability and ER stress leading to depletion of the neural progenitor pool and neurodegeneration. Surprisingly, we also observed inhibition of autophagy in RINT1-deficient neurons, indicating an involvement of RINT1 in the regulation of neuronal autophagy. Here, we summarize our main RINT1 findings and discuss its putative roles in autophagy. PMID- 27367499 TI - Frequency, Phenotypic Characteristics and Progression of Atrophy Associated With a Diseased Bruch's Membrane in Pseudoxanthoma Elasticum. AB - PURPOSE: To characterize atrophy of the outer retina and the retinal pigment epithelium in patients with pseudoxanthoma elasticum (PXE). METHODS: In this retrospective cross-sectional study, the frequency and phenotypic characteristics of manifest atrophy were investigated in 276 eyes of 139 patients using color fundus photography, fundus autofluorescence (AF) imaging, and spectral domain optical coherence tomography. Progression rates of atrophy were quantified in eyes with longitudinal AF recordings. RESULTS: Atrophy was present in 90 eyes (32%; mean age, 60; range, 32-88 years). In 19 eyes (7%; mean age, 56; range, 37 77 years) atrophy occurred without any signs for an active or fibrotic choroidal neovascularization (CNV). The frequency of both, atrophy and CNV, increased with age. In those > 60 years of age, atrophy and/or CNV were almost universally present but varied considerably in severity. Eyes with emerging pure atrophy (n = 13, no signs of CNV) showed pattern dystrophy-like changes (100%), reticular pseudodrusen (82%), and reduced choroidal thickness. Advanced atrophy was multifocal, reached beyond the arcades, and was present nasal to the optic disc. The average expansion rate of atrophy was 3.3 +/- 1.3 and 1.6 +/- 1.1 mm2/year (mean +/- SD), in those without or with signs for CNV, respectively. CONCLUSIONS: Atrophy of the outer retina and the retinal pigment epithelium is a common finding in PXE patients characterized by early onset and fast progression with subsequent visual loss independent from CNV. This suggests that atrophy is the natural endpoint of Bruch's membrane disease. Phenotypic similarities with multifactorial geographic atrophy in age-related macular degeneration suggest common pathogenic pathways at the level of Bruch's membrane. PMID- 27367501 TI - Patients With Intravitreal Gas Bubbles at Risk of High Intraocular Pressure Without Exceeding Elevation of Surgery: Theoretical Analysis. AB - PURPOSE: The purpose of this study was to show the mechanism responsible for high peak IOP in patients with intravitreal gas bubbles resulting from a descent to low elevation and a return ascent, without exceeding the surgical elevation. METHODS: A computational model reconstructed four clinical cases, using published elevations, ascent rates, and initial bubble sizes. In each case, patients first underwent surgery (790 m), then went home (790 m, 790 m, 325 m, 240 m). When returning for follow-up visits, patients descended to a low elevation (20 m, 0 m, 25 m, -310 m), then ascended to surgical elevation (790 m). The computational model output bubble size, aqueous humor volume, and IOP during the patients' travels. A parametric study was conducted to investigate the role of each modeling parameter. RESULTS: All four simulated cases showed increased peak IOP (34-50 mm Hg). Intraocular pressure returned to a normal value (15 mm Hg) after prolonged exposure to the surgical elevation. Over the course of the entire path, the gas bubble volume changed approximately 5%, decreasing in size during descent and then increasing during ascent. CONCLUSIONS: In our simulations the change of bubble size outpaced the change of aqueous humor volume resulting in a 2-fold risk to patients. First, the bubble size reduction at the low elevation may increase the risk of ocular hypotony and postsurgical retinal detachment. Second, the combined increasing bubble size and accumulated aqueous humor puts patients at risk of high peak IOP after ascent even without exceeding the surgical elevation. The risks are primarily dependent on rates of elevation change and duration spent at the different elevations. PMID- 27367500 TI - Displacement of the Lamina Cribrosa in Response to Acute Intraocular Pressure Elevation in Normal Individuals of African and European Descent. AB - PURPOSE: To assess if the in vivo mechanical displacement of the anterior laminar cribrosa surface (ALCS) as a response of an acute elevation in intraocular pressure (IOP) differs in individuals of European (ED) and African descent (AD). METHODS: Spectral-domain optical coherence tomography (SDOCT) scans were obtained from 24 eyes of 12 individuals of AD and 18 eyes of 9 individuals of ED at their normal baseline IOP and after 60 seconds IOP elevation using ophthalmodynamometry. Change in depth (displacement) of the LC and to the prelaminar tissue (PLT) were computed in association with the change (delta) in IOP (Delta IOP), race, age, corneal thickness, corneal rigidity (ocular response analyzer [ORA]), and axial. RESULTS: In the ED group for small IOP elevations (Delta IOP < 12 mm Hg), the ALCS initially displaced posteriorly but for larger increase of IOP an anterior displacement of the lamina followed. Inversely, in the AD group the ALCS did not show a significant posterior displacement for small Delta IOP, while for larger IOP increases the ALCS significantly displaced posteriorly. Posterior displacement of the lamina cribrosa (LC) was also significantly correlated with longer axial length, higher corneal thickness, and ORA parameters. Prelaminar tissue posteriorly displaced for any magnitude of Delta IOP, in both groups. CONCLUSIONS: The African descent group demonstrated a greater acute posterior bowing of the LC after adjustment for age, axial length, Bruch's membrane opening (BMO) area, and ORA parameters. Greater PLT posterior displacement was also seen in the AD group with increasing IOP, which was tightly correlated with the displacement of the LC. PMID- 27367502 TI - Generation of Retinal Ganglion Cells With Functional Axons From Mouse Embryonic Stem Cells and Induced Pluripotent Stem Cells. AB - PURPOSE: We previously generated self-induced retinal ganglion cells (RGCs) with functional axons from human induced pluripotent stem cells (hiPSCs). We investigated whether self-induced RGCs from mouse embryonic stem cells (mESCs) and induced pluripotent stem cells (miPSCs) are realized by the similar induction protocol. METHODS: Retinal ganglion cells were induced using a protocol in which floating embryoid bodies (EBs) were differentiated into a retinal cell lineage in three-dimensional culture and subsequently attached to two-dimensional culture dishes with brain-derived neurotrophic factor (BDNF) supplementation. RESULTS: Retinal ganglion cells developed in an attached clump of cells originating from the optic vesicle, and most axons grew from RGC cell bodies at the margins of the clump. The differentiation of RGCs was confirmed by the expression of specific markers, including Brn3a and Math5. The axons contained neurofilament subtypes and tau, and manifested axonal transport and sodium-dependent action potentials. The RGCs derived from mESCs and miPSCs generally showed similar profiles, including RNA and protein expression levels and function. CONCLUSIONS: Retinal ganglion cells generated from mESCs and miPSCs, especially the latter, may contribute to research associated with RGCs and to in vitro analyses of genetically modified mice. PMID- 27367503 TI - Coordinated Regulation of Palladin and alpha-Smooth Muscle Actin by Transforming Growth Factor-beta in Human Corneal Fibroblasts. AB - PURPOSE: To investigate the role of palladin in the cornea, we examined expression of this actin assembly-related protein in normal, diseased, or injured corneal tissue as well as in cultured corneal fibroblasts. METHODS: Expression of palladin and alpha-smooth muscle actin (alpha-SMA) in the rat cornea with an incision wound, in the normal and diseased human cornea, and in cultured human corneal fibroblasts was examined by immunofluorescence or immunoblot analysis. RESULTS: The expression of both palladin and alpha-SMA was detected at the lesion site during wound healing in the rat cornea. Whereas neither palladin nor alpha SMA was detected in the normal human cornea, the colocalization of both proteins was detected in diseased human corneas with underlying conditions characterized by the presence of fibrosis. The expression of both palladin and alpha-SMA in cultured human corneal fibroblasts was increased by transforming growth factor beta (TGF-beta) in a manner sensitive to inhibition by blockers of Smad or mitogen-activated protein kinase (MAPK) signaling. Finally, RNA interference mediated depletion of palladin attenuated the TGF-beta-induced upregulation of alpha-SMA expression in human corneal fibroblasts as well as TGF-beta-induced collagen gel contraction mediated by these cells. CONCLUSIONS: Palladin is expressed in the rat and human cornea in association with scar formation. Expression of palladin in human corneal fibroblasts is increased by TGF-beta in a manner dependent on Smad and MAPK signaling and is required for the TGF-beta induced upregulation of alpha-SMA. PMID- 27367504 TI - Beneficial Effects of Berberine on Oxidized LDL-Induced Cytotoxicity to Human Retinal Muller Cells. AB - PURPOSE: Limited mechanistic understanding of diabetic retinopathy (DR) has hindered therapeutic advances. Berberine, an isoquinolone alkaloid, has shown favorable effects on glucose and lipid metabolism in animal and human studies, but effects on DR are unknown. We previously demonstrated intraretinal extravasation and modification of LDL in human diabetes, and toxicity of modified LDL to human retinal Muller cells. We now explore pathogenic effects of modified LDL on Muller cells, and the efficacy of berberine in mitigating this cytotoxicity. METHODS: Confluent human Muller cells were exposed to in vitro modified 'highly oxidized, glycated (HOG-) LDL versus native-LDL (N-LDL; 200 mg protein/L) for 6 or 24 hours, with/without pretreatment with berberine (5 MUM, 1 hour) and/or the adenosine monophosphate (AMP)-activated protein kinase (AMPK) inhibitor, Compound C (5 MUM, 1 hour). Using techniques including Western blots, reactive oxygen species (ROS) detection assay, and quantitative real-time PCR, the following outcomes were assessed: cell viability (CCK-8 assay), autophagy (LC3, Beclin-1, ATG-5), apoptosis (cleaved caspase 3, cleaved poly-ADP ribose polymerase), oxidative stress (ROS, nuclear factor erythroid 2-related factor 2, glutathione peroxidase 1, NADPH oxidase 4), angiogenesis (VEGF, pigment epithelium-derived factor), inflammation (inducible nitric oxide synthase, intercellular adhesion molecule 1, IL-6, IL-8, TNF-alpha), and glial cell activation (glial fibrillary acidic protein). RESULTS: Native-LDL had no effect on cultured human Muller cells, but HOG-LDL exhibited marked toxicity, significantly decreasing viability and inducing autophagy, apoptosis, oxidative stress, expression of angiogenic factors, inflammation, and glial cell activation. Berberine attenuated all the effects of HOG-LDL (all P < 0.05), and its effects were mitigated by AMPK inhibition (P < 0.05). CONCLUSIONS: Berberine inhibits modified LDL-induced Muller cell injury by activating the AMPK pathway, and merits further study as an agent for preventing and/or treating DR. PMID- 27367505 TI - Is Retinal Dopamine Involved in the Loss of Visual Function in Retinopathy of Prematurity? PMID- 27367507 TI - In Vivo Fluorescence Retinal Imaging Following AAV2-Mediated Gene Delivery in the Rat Retina. AB - PURPOSE: The purpose of this study was to evaluate longitudinal gene expression patterns by retinal imaging using a modified custom-built confocal laser-scanning microscope in experimental rats after intravitreal injection of recombinant adeno associated virus 2 (rAAV2-green fluorescent protein [GFP]). METHODS: Ten 9-week old Wistar rats were divided into two groups: experimental group (group 1) that received a rAAV2-GFP intravitreal injection and control group (group 2) that received a vehicle. After anesthesia using a Zoletil intraperitoneal injection, 8 MUL rAAV2-GFP in group 1 or vehicle in group 2 was injected intravitreally using a 33-G Hamilton syringe. In vivo fluorescence retinal images were acquired under anesthesia at 2, 4, 6, and 13 days after rAAV or vehicle delivery. RESULTS: Differences in GFP fluorescence were identified starting from day 2 after the intravitreal injection of rAAV2-GFP in group 1. Between days 4 and 6, the intensity and area of fluorescence in the retina began to increase and peaked at day 13. Based on the pattern of GFP expression, the axon of the nerve fiber layer ganglion cell was identified. In group 2, eyes treated with the vehicle showed a small amount of autofluorescence in a limited area for up to 2 weeks, with no increase in intensity during this period. CONCLUSIONS: In vivo retinal imaging confirmed gene expression within 2 weeks after the intravitreal injection of rAAV2-GFP. Gene transfer and expression in the rat retina occurs quickly in 2 days and appears to peak within 2 weeks of gene delivery. In vivo retinal imaging may be a useful noninvasive tool to continuously monitor gene expression in the retina over time. PMID- 27367506 TI - Epigenetic Modification Prevents Excessive Wound Healing and Scar Formation After Glaucoma Filtration Surgery. AB - PURPOSE: The purpose of this study was to determine the efficacy of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACi), in prevention of excessive wound healing and scar formation in a rabbit model of glaucoma filtration surgery (GFS). METHODS: A rabbit model of GFS was used. Rabbits that underwent GFS received balanced salt solution, or SAHA (50 MUM), or mitomycin C (0.02%). Clinical scores of IOP, bleb vascularity, and slit-lamp examination were performed. On postoperative day 14, rabbits were killed and the bleb tissues were collected for evaluation of tissue fibrosis with hematoxylin and eosin, Masson trichrome, alpha-smooth muscle actin (alphaSMA), and F-actin staining. Furthermore, SAHA-mediated acetylation of histones in corneal fibroblasts and conjunctiva were determined by Western blot analysis. RESULTS: Suberoylanilide hydroxamic acid treatment after GFS showed no signs of edema, corneal opacity, endophthalmitis, or cataract formation. Morphometric analysis of SAHA-treated eyes showed higher bleb length (P < 0.001), bleb area (P < 0.05), lower IOP (P < 0.01), and decreased vascularity compared to control. Furthermore, SAHA treatment showed significantly reduced levels of alphaSMA (P < 0.001), F actin (P < 0.01), and collagen deposition (P < 0.05) at the sclerotomy site. In addition, SAHA treatment increased the acetylation status of H3 and H4 histones in corneal fibroblasts and conjunctiva. CONCLUSIONS: This study demonstrates that HDAC inhibition is an attractive pharmacologic target to modulate GFS wound healing, and SAHA, an HDACi, can be a useful adjunct to improve the GFS outcome. PMID- 27367508 TI - Characterization of Fatty Acid Binding Protein 7 (FABP7) in the Murine Retina. AB - PURPOSE: To characterize the mouse retina lacking fatty acid binding protein (FABP7-/-). METHODS: Immunohistochemistry (IHC) was performed in 8-week-old mice to localize FABP7 in the retina. Retinal thickness was measured using image guided spectral-domain optical coherence topography images. Electroretinography was carried out to assess retinal function. Fundus photography and fundus fluorescein angiography were performed on FABP7-/- and littermate wild-type (WT) mice, and retinal vascular changes were calculated using Singapore I Vessel Assessment (SIVA) analysis. Blood glucose levels were measured in the 8-week-old WT and FABP7-/- mice. In addition, retina was processed for trypsin digestion and retinal flat mounts for isolectin staining. Transcript levels of FABP7, VEGF, GFAP, and Na+K+ATPase were quantified using real-time PCR, and protein expression was analyzed by IHC and Western blot. RESULTS: Fatty acid binding protein 7 is expressed in the inner nuclear layer, outer plexiform layer, and photoreceptor inner segments. No significant difference in retinal thickness and ERG responses was observed between FABP7-deficient and WT retinas. FABP7-/- mice have significantly decreased retinal venular caliber retinal arteriolar fractal dimension compared with WT littermates. FABP7-/- mice showed significant increased areas of fluorescein leakage in the retina. FABP7-/- mice exhibited elevated high blood glucose levels compared with WT mice. Trypsin digested FABP7 /- mice retina showed increased acellular strands and endothelial cell drop outs, and reduced microvasculature branching compared with WT retina. FABP7-/- mice retina also have increased GFAP and VEGF expression. CONCLUSIONS: Fatty acid binding protein 7 is expressed in the retina and might play an important role in maintaining retinal vasculature. PMID- 27367510 TI - Genetic Association at the 9p21 Glaucoma Locus Contributes to Sex Bias in Normal Tension Glaucoma. AB - PURPOSE: Many genome-wide association studies have identified common single nucleotide polymorphisms (SNPs) at the 9p21 glaucoma locus (CDKN2B/CDKN2B-AS1) to be significantly associated with primary open-angle glaucoma (POAG), with association being stronger in normal tension glaucoma (NTG) and advanced glaucoma. We aimed to determine whether any observed differences in genetic association at the 9p21 locus are influenced by sex. METHODS: Sex was assessed as a risk factor for POAG for 2241 glaucoma participants from the Australian and New Zealand Registry of Advanced Glaucoma, the Glaucoma Inheritance Study in Tasmania, and the Flinders Medical Centre. A total of 3176 controls were drawn from the Blue Mountains Eye Study and South Australia: 1523 advanced POAG and 718 nonadvanced POAG cases were genotyped along with 3176 controls. We selected 13 SNPs at the 9p21 locus, and association results were subanalyszd by sex for high tension glaucoma (HTG) and NTG. Odds ratios (ORs) between sexes were compared. RESULTS: A sex bias was present within advanced NTG cases (57.1% female versus 42.9% male, P = 0.0026). In all POAG cases, the strongest associated SNP at 9p21 was rs1063192 (OR, 1.43; P = 4 * 10-18). This association was stronger in females (OR, 1.5; P = 5 * 10-13) than in males (OR, 1.35; P = 7 * 10-7), with a statistically significant difference in female to male OR comparison (P = 1.0 * 10-2). An NTG to HTG subanalysis yielded statistically significant results only in females (OR, 1.63; P = 1.5 * 10-4) but not in males (OR, 1.15; P = 2.8 * 10 1), with a statistically significant difference in female to male OR comparison (P = 1.4 * 10-4). CONCLUSIONS: This study demonstrated that female sex is a risk factor for developing advanced NTG. The stronger genetic signals at the 9p21 locus among females may contribute at least in part to the observed sex bias for NTG. PMID- 27367511 TI - Mirror Symmetry of Peripheral Monochromatic Aberrations in Fellow Eyes of Isomyopes and Anisomyopes. AB - PURPOSE: To investigate mirror symmetry of peripheral ocular aberrations in fellow eyes of iso- and anisomyopes. METHODS: Peripheral aberration was measured over the central 42 degrees * 32 degrees visual field for a 5-mm pupil in both eyes of 19 isomyopic (spherical equivalent refraction M [right/left]: -2.5 +/- 2.1 diopters [D]/-2.7 +/- 2.3 D) and 10 anisomyopic (M: -4.0 +/- 1.8 D/-4.3 +/- 2.8 D) young adults. Isomyopes had less than 1.0 D fellow eye refraction difference and anisomyopes had between 1.0 D and 2.6 D fellow eye differences (mean difference: 1.3 +/- 0.6 D). Orthogonal regression of Zernike coefficients determined right-left eye correlations in isomyopes. For anisomyopes, higher and lower myopic eye coefficients were compared. RESULTS: For isomyopes, the percentages of visual field locations with significant coefficient correlations between fellow eyes varied from 100% for astigmatism ( ) to 18% for tetrafoil ( ). Positive correlations were found for , , , , , and , and negative correlations were found for , , , , and coefficients, indicating that the signs are different for corresponding locations of fellow eyes for the last five of these coefficients. Slopes of correlations were not different from +/- 1, except for , , and (+0.95, -0.97, and +0.52, respectively). In anisomyopes, significant but small fellow eye differences were found for only and coefficients, with significant interactions between anisometropia and field position for only two coefficients. CONCLUSIONS: Peripheral aberration coefficients across the visual field show mirror symmetry in isomyopes, and in a pooled data set the coefficients with negative correlations require sign changes for left eye data. Anisometropia contributes no more to peripheral aberration differences between fellow eyes than could be expected on the basis of refraction differences between people. PMID- 27367509 TI - Simultaneous Expression of ABCA4 and GPR143 Mutations: A Complex Phenotypic Manifestation. AB - PURPOSE: To describe the complex, overlapping phenotype expressed in a two generation family harboring pathogenic mutations in the ABCA4 and GPR143 genes. METHODS: Clinical evaluation of a two generation family included quantitative autofluorescence imaging (qAF, 488-nm excitation) using a modified confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for varying laser power detector sensitivity, spectral-domain optical coherence tomography, and full-field ERG testing. Complete sequencing of the ABCA4 and GPR143 genes was carried out in each individual. RESULTS: Affected individuals presented with bull's eye lesions and qAF levels above the 95% confidence interval for healthy eyes; full-field ERG revealed no generalized rod dysfunction but mild implicit time delays in cone responses. Complete sequencing of the ABCA4 gene revealed two disease-causing mutations, p.L541P and p.G1961E; and mutational phase was confirmed in each unaffected parent. Further examination in the affected patients revealed a peripheral "mud-splattered" pattern of hypopigmented RPE after which sequencing of GPR143 revealed a novel missense variant, p.Y157C. The GPR143 variant segregated from the father who did not exhibit any indications of retinal disease with the exception of an abnormal near infrared autofluorescence (NIR-AF) signal distribution in the macula. CONCLUSIONS: An individual carrying both ABCA4 and GPR143 disease-causing mutations can express a complex, overlapping phenotype associated with both Stargardt disease and X-linked ocular albinism (OA1). The absence of OA1-related disease changes (with the exception of NIR-AF changes associated with melanin distribution) in the father may be indicative of mild expressivity or variable gene penetrance. PMID- 27367513 TI - AAV-Mediated CRISPR/Cas Gene Editing of Retinal Cells In Vivo. AB - PURPOSE: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) has recently been adapted to enable efficient editing of the mammalian genome, opening novel avenues for therapeutic intervention of inherited diseases. In seeking to disrupt yellow fluorescent protein (YFP) in a Thy1-YFP transgenic mouse, we assessed the feasibility of utilizing the adeno-associated virus 2 (AAV2) to deliver CRISPR/Cas for gene modification of retinal cells in vivo. METHODS: Single guide RNA (sgRNA) plasmids were designed to target YFP, and after in vitro validation, selected guides were cloned into a dual AAV system. One AAV2 construct was used to deliver Streptococcus pyogenes Cas9 (SpCas9), and the other delivered sgRNA against YFP or LacZ (control) in the presence of mCherry. Five weeks after intravitreal injection, retinal function was determined using electroretinography, and CRISPR/Cas-mediated gene modifications were quantified in retinal flat mounts. RESULTS: Adeno-associated virus 2-mediated in vivo delivery of SpCas9 with sgRNA targeting YFP significantly reduced the number of YFP fluorescent cells of the inner retina of our transgenic mouse model. Overall, we found an 84.0% (95% confidence interval [CI]: 81.8-86.9) reduction of YFP-positive cells in YFP-sgRNA infected retinal cells compared to eyes treated with LacZ-sgRNA. Electroretinography profiling found no significant alteration in retinal function following AAV2-mediated delivery of CRISPR/Cas components compared to contralateral untreated eyes. CONCLUSIONS: Thy1-YFP transgenic mice were used as a rapid quantifiable means to assess the efficacy of CRISPR/Cas-based retinal gene modification in vivo. We demonstrate that genomic modification of cells in the adult retina can be readily achieved by viral-mediated delivery of CRISPR/Cas. PMID- 27367512 TI - Expression Profiling of Ascorbic Acid-Related Transporters in Human and Mouse Eyes. AB - PURPOSE: Ascorbic acid (AsA) is an important antioxidant in the eye. Ascorbic acid is usually transported by sodium-dependent AsA transporters (SVCTs), and dehydroascorbic acid (DHA) by glucose transporters (GLUTs). This study investigates these AsA-related transporters in human compared with mouse eyes. METHODS: Five pairs of human donor eyes and 15 pairs of mouse eyes were collected. Immunofluorescence and in situ hybridization were performed to detect SVCTs and GLUTs expression in the ciliary epithelium, retina, and lens epithelial cells (LECs). These tissues were isolated with laser microdissection followed by extraction of total RNA. Quantitative PCR (qPCR) was performed to examine the mRNA level of SVCTs and GLUTs in human and mouse ocular tissues. RESULTS: Immunofluorescence and in situ hybridization showed SVCT2 and GLUT1 expression in human ciliary epithelium with varied distributions. Sodium-dependent AsA transporter 2 is expressed only in the pigmented epithelium (PE), and GLUT1 is predominately expressed in the nonpigmented epithelium (NPE). However, SVCT2 was not identified in mouse ciliary epithelium, whereas GLUT1 expressed in both PE and NPE. Laser microdissection and qPCR revealed high levels of SVCT2 mRNA in human RPE cells and murine neural retina. Sodium-dependent AsA transporter 1 mRNA could be detected only in human and murine LECs. Glucose transporter 3 and GLUT4 mRNA could not be detected in either the human or mouse ciliary processes or in the lens epithelium. CONCLUSIONS: These fundamental findings indicate AsA transporter expression in eyes of humans is significantly different compared with mice. This may explain why human aqueous and vitreous humors contain higher AsA levels compared with other animals. PMID- 27367514 TI - Longitudinal Changes to Tight Junction Expression and Endothelial Cell Integrity in a Mouse Model of Sterile Corneal Inflammation. AB - PURPOSE: We previously reported that applying toll-like receptor (TLR) ligands to an injured cornea induces corneal edema at 24 hours, which subsides by 1 week. We tested the hypotheses that endothelial expression of the tight-junction protein, zonula occludens-1 (ZO-1), would be altered during experimental sterile corneal inflammation and that endothelial cell density (ECD) would remain unaffected. METHODS: Anesthetized C57BL/6J mice received central 1-mm corneal abrasions followed by topical application of saline or cytosine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN, TLR-9 agonist). At 24 hours, 1 week and 4 weeks post treatment, spectral-domain optical coherence tomography images were captured. Eyes were enucleated and processed for zonula occludens-1 (ZO-1) immunofluorescent staining. Corneal flatmounts were analyzed for endothelial ZO-1 expression, cell density, polymegethism, and polymorphism. Corneal stromal inflammatory cell infiltration was evaluated at 4 weeks by immunostaining for CD45. RESULTS: Central corneal thickness (CCT) was increased in CpG-ODN treated eyes at 24 hours, had normalized by 1 week, but was again thickened by 4 weeks. In eyes with CpG-ODN, endothelial cell ZO-1 expression was reduced at 24 hours but returned to normal levels by 1 week. Endothelial cell density was not altered at 24 hours or 1 week. By 4 weeks, only CpG-ODN eyes showed relatively reduced ECD, as well as large numbers of CD45+ cells in the stroma. Changes to ECD correlated with CCT (r = -0.53, P < 0.01). Compared with naive controls, more saline- and CpG-ODN-treated eyes exhibited polymegethism. CONCLUSIONS: This study provides novel insights into the interplay between endothelial cell integrity, corneal edema, and chronic stromal leukocyte activation during sterile corneal inflammation in mice. PMID- 27367515 TI - Longitudinal Changes to Tight Junction Expression and Endothelial Cell Integrity in a Mouse Model of Sterile Corneal Inflammation. PMID- 27367516 TI - Retinal Pigment Epithelium Responses to Selective Retina Therapy in Mouse Eyes. AB - PURPOSE: To investigate the characteristics of retinal pigment epithelium (RPE) and retinal damage induced by selective retina therapy (SRT) in mice, and to elucidate longitudinal changes in RPE cells. METHODS: C57BL/6J mice received SRT and continuous-wave laser photocoagulation (cwPC). The cell death pattern was evaluated using TUNEL assay, and proliferative potential of the RPE cells was evaluated using 5-ethynyl-2'-dexoyuridine (EdU) assay. To investigate the cell cell integrity of RPE cells, beta-catenin staining was performed. The number and hexagonality of RPE cells in the SRT-treated area were estimated using a Voronoi diagram with time periods of 3 hours to 14 days. Antibodies to microphthalmia associated transcription factor (MiTF) and orthodenticle homeobox 2 (Otx2) were used to confirm the specific characteristics of RPE cells in the SRT-treated area. RESULTS: The number of TUNEL-positive cells located in the neural retina was significantly lower in lesions treated with SRT compared to those treated with cwPC. EdU-positive RPE cells were first detected 3 to 12 hours after SRT, and increased until 3 to 7 days after SRT. beta-catenin staining showed that hexagonality was compromised and subsequently, RPE cells expanded in size within the targeted location. The number of RPE cells in SRT lesions decreased gradually until 12 hours after SRT and recovered by 14 days. Upregulated expression of MiTF and Otx2 was observed for 2 weeks in the SRT lesions. CONCLUSIONS: Selective retina therapy seems to induce selective RPE damage without collateral thermal injury in the neural retina. Furthermore, SRT-treated lesions recovered by proliferation of RPE cells that were present in the treated lesions and by expansion of adjacent RPE cells. PMID- 27367517 TI - Early Functional and Morphologic Abnormalities in the Diabetic Nyxnob Mouse Retina. AB - PURPOSE: The electroretinogram c-wave is generated by the summation of the positive polarity hyperpolarization of the apical RPE membrane and a negative polarity slow PIII response of Muller glia cells. Therefore, the c-wave reduction noted in prior studies of mouse models of diabetes could reflect a reduction in the RPE component or an increase in slow PIII. The present study used a genetic approach to distinguish between these two alternatives. METHODS: Nyxnob mice lack the ERG b-wave, revealing the early phase of slow PIII. To visualize changes in slow PIII due to diabetes, Nyxnob mice were given streptozotocin (STZ) injections to induce diabetes or received vehicle as a control. After 1, 2, and 4 weeks of sustained hyperglycemia (>250 mg/dL), standard strobe flash ERG and dc-ERG testing were conducted. Histological analysis of the retina was performed. RESULTS: A reduced c-wave was noted at the 1 week time point, and persisted at later time points. In comparison, slow PIII amplitudes were unaffected after 1 week of hyperglycemia, but were significantly reduced in STZ mice at the 2-week time point. The decrease in amplitude occurred before any identifiable decrease to the a-wave. At the later time point, the a-wave became involved, although the slow PIII reductions were more pronounced. Morphological abnormalities in the RPE, including increased thickness and altered melanosome distribution, were identified in diabetic animals. CONCLUSIONS: Because the c-wave and slow PIII were both reduced, these results demonstrated that diabetes-induced reductions to the c-wave cannot be attributed to an early increase in the Muller glia-derived potassium conductance. Furthermore, because the a-wave, slow PIII and c-wave reductions were not equivalent, and varied in their onset, the reductions cannot reflect the same mechanism, such as a change in membrane resistance. The presence of small changes to RPE architecture indicate that the c-wave reductions present in diabetic mice likely represents a primary change in the RPE induced by hyperglycemia. PMID- 27367518 TI - Upper Extremity Functional Evaluation by Fugl-Meyer Assessment Scoring Using Depth-Sensing Camera in Hemiplegic Stroke Patients. AB - Virtual home-based rehabilitation is an emerging area in stroke rehabilitation. Functional assessment tools are essential to monitor recovery and provide current function-based rehabilitation. We developed the Fugl-Meyer Assessment (FMA) tool using Kinect (Microsoft, USA) and validated it for hemiplegic stroke patients. Forty-one patients with hemiplegic stroke were enrolled. Thirteen of 33 items were selected for upper extremity motor FMA. One occupational therapist assessed the motor FMA while recording upper extremity motion with Kinect. FMA score was calculated using principal component analysis and artificial neural network learning from the saved motion data. The degree of jerky motion was also transformed to jerky scores. Prediction accuracy for each of the 13 items and correlations between real FMA scores and scores using Kinect were analyzed. Prediction accuracies ranged from 65% to 87% in each item and exceeded 70% for 9 items. Correlations were high for the summed score for the 13 items between real FMA scores and scores obtained using Kinect (Pearson's correlation coefficient = 0.873, P<0.0001) and those between total upper extremity scores (66 in full score) and scores using Kinect (26 in full score) (Pearson's correlation coefficient = 0.799, P<0.0001). Log transformed jerky scores were significantly higher in the hemiplegic side (1.81 +/- 0.76) compared to non-hemiplegic side (1.21 +/- 0.43) and showed significant negative correlations with Brunnstrom stage (3 to 6; Spearman correlation coefficient = -0.387, P = 0.046). FMA using Kinect is a valid way to assess upper extremity function and can provide additional results for movement quality in stroke patients. This may be useful in the setting of unsupervised home-based rehabilitation. PMID- 27367519 TI - Clarifying Scar Revision Techniques and Their Proper Use-Reply. PMID- 27367520 TI - Aberrant trafficking of a Leu89Pro connexin32 mutant associated with X-linked dominant Charcot-Marie-Tooth disease. AB - OBJECTIVE: To determine the functional abnormalities of the Leu89Pro mutation in connexin32 (CX32), which we have previously reported is present within an X linked dominant Charcot-Marie-Tooth disease family. In this family, male patients were moderately to severely affected. METHODS: We performed immunofluorescence to investigate whether the Leu89Pro CX32 protein was transported to the cell membrane in HeLa and Schwann cells. First, we constructed the eukaryotic express plasmids expressing CX32 (wild-type or Leu89Pro) and enhanced green fluorescent protein by the gene recombination technology. Then the recombinant plasmids were transiently transfected into communication-incompetent HeLa cells and human Schwann cells by the lipofectamine method. Later, we double-labeled cells for both CX32 and markers of the ER (calnexin) or the Golgi (58-kDa protein) at 24 h or 48 h. The images were collected using a Leica TCS SP5 II confocal microscope. RESULTS: The mutant CX32 protein was localized in the endoplasmic reticulum and failed to reach the cell membrane to form gap junctions. CONCLUSION: Our results indicated that the Leu89Pro substitution in the second transmembrane domain of CX32 disrupts the trafficking of the protein, inhibiting the assembly of CX32 gap junctions, which in turn may result in peripheral neuropathy. This functional abnormality may explain the moderate to severe phenotype seen in Leu89Pro patients, and as such represents a promising therapeutic target in the treatment of this subset of CMTX patients. PMID- 27367521 TI - Tuberculosis Therapy Modifies the Cytokine Profile, Maturation State, and Expression of Inhibitory Molecules on Mycobacterium tuberculosis-Specific CD4+ T Cells. AB - BACKGROUND: Little is known about the expression of inhibitory molecules cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed-death-1 (PD-1) on Mycobacterium tuberculosis (Mtb)-specific CD4 T-cells and how their expression is impacted by TB treatment. METHODS: Cryopreserved PBMCs from HIV-TB co-infected and TB mono-infected patients with untreated and treated tuberculosis (TB) disease were stimulated for six hours with PPD and stained. Using polychromatic flow cytometry, we characterized the differentiation state, cytokine profile, and inhibitory molecule expression on PPD-specific CD4 T-cells. RESULTS: In our HIV TB co-infected cohort, TB treatment increased the proportion of PPD-specific CD4 T-cells co-producing IFN-gamma+IL-2+TNF-alpha+ and IFN-gamma+IL-2+ (p = 0.0004 and p = 0.0002, respectively) while decreasing the proportion of PPD-specific CD4 T-cells co-producing IFN-gamma+MIP1-beta+TNF-alpha+ and IFN-gamma+MIP1-beta+. The proportion of PPD-specific CD4 T-cells expressing an effector memory phenotype decreased (63.6% vs 51.6%, p = 0.0015) while the proportion expressing a central memory phenotype increased (7.8% vs. 21.7%, p = 0.001) following TB treatment. TB treatment reduced the proportion of PPD-specific CD4 T-cells expressing CTLA-4 (72.4% vs. 44.3%, p = 0.0005) and PD-1 (34.5% vs. 29.2%, p = 0.03). Similar trends were noted in our TB mono-infected cohort. CONCLUSION: TB treatment alters the functional profile of Mtb-specific CD4 T-cells reflecting shifts towards a less differentiated maturational profile and decreases PD-1 and CTLA-4 expression. These could serve as markers of reduced mycobacterial burden. Further study is warranted. PMID- 27367522 TI - Components of One-carbon Metabolism Other than Folate and Colorectal Cancer Risk. AB - BACKGROUND: Despite extensive study, the role of folate in colorectal cancer remains unclear. Research has therefore begun to address the role of other elements of the folate-methionine metabolic cycles. This study investigated factors other than folate involved in one-carbon metabolism, i.e., choline, betaine, dimethylglycine, sarcosine, and methionine and relevant polymorphisms, in relation to the risk of colorectal cancer in a population with low intakes and circulating levels of folate. METHODS: This was a prospective case-control study of 613 case subjects and 1,190 matched control subjects nested within the population-based Northern Sweden Health and Disease Study. We estimated odds ratios (OR) by conditional logistic regression, and marginal risk differences with weighted maximum likelihood estimation using incidence data from the study cohort. RESULTS: Higher plasma concentrations of methionine and betaine were associated with modest colorectal cancer risk reductions (OR [95% confidence interval {CI}] for highest versus lowest tertile: 0.76 [0.57, 0.99] and 0.72 [0.55, 0.94], respectively). Estimated marginal risk differences corresponded to approximately 200 fewer colorectal cancer cases per 100,000 individuals on average. We observed no clear associations between choline, dimethylglycine, or sarcosine and colorectal cancer risk. The inverse association of methionine was modified by plasma folate concentrations (OR [95% CI] for highest/lowest versus lowest/lowest tertile of plasma methionine/folate concentrations 0.39 [0.24, 0.64], Pinteraction = 0.06). CONCLUSIONS: In this population-based, nested case control study with a long follow-up time from baseline to diagnosis (median: 8.2 years), higher plasma concentrations of methionine and betaine were associated with lower colorectal cancer risk.See Video Abstract at http://links.lww.com/EDE/B83. PMID- 27367523 TI - Relationships between Body Size and Parasitic Fitness and Offspring Performance of Sclerodermus pupariae Yang et Yao (Hymenoptera: Bethylidae). AB - The relationship between body size and fitness in parasitoid wasps has several effects on parasitic ability, reproductive behavior in female wasps, and progeny fitness. Female wasps with various body sizes were obtained by mass-rearing a gregarious ectoparasitoid, Sclerodermus pupariae, which is one of the excellent parasites to control the larvae and pupae of Buprestidae and Cerambycidae. We investigated the effects of body size of adult females introduced on Thyestilla gebleri (Coleoptera: Cerambycidae) larvae on their paralysis time, pre oviposition period, oviposition period and fecundity, and the related fitness of their offspring. Results showed that small female wasps needed more time to paralyze a host and had a higher mortality rate than large female wasps. More offspring were produced by large female wasps than by small female wasps, and the percentage and body size of female offspring was not affected by maternal body size. The duration of the egg stage was not affected by foundress size, nor was that of the pupal stage, but the duration of the larval stage and generation time of small female wasps was longer than that of large females. Our findings suggest that the parasitic fitness and offspring performance are affected by maternal size, and there is need to choose reasonable body size of female wasps, to optimally utilize mass rearing and to control target pests with the lowest mortality cost. PMID- 27367524 TI - Biography: John Meurig Thomas. PMID- 27367525 TI - Monitoring the aeration efficiency and carbon footprint of a medium-sized WWTP: experimental results on oxidation tank and aerobic digester. AB - The efficiency of aeration systems should be monitored to guarantee suitable biological processes. Among the available tools for evaluating the aeration efficiency, the off-gas method is one of the most useful. Increasing interest towards reducing greenhouse gas (GHG) emissions from biological processes has resulted in researchers using this method to quantify N2O and CO2 concentrations in the off-gas. Experimental measurements of direct GHG emissions from aerobic digesters (AeDs) are not available in literature yet. In this study, the floating hood technique was used for the first time to monitor AeDs. The floating hood technique was used to evaluate oxygen transfer rates in an activated sludge (AS) tank of a medium-sized municipal wastewater treatment plant located in Italy. Very low values of oxygen transfer efficiency were found, confirming that small to-medium-sized plants are often scarcely monitored and wrongly managed. Average CO2 and N2O emissions from the AS tank were 0.14 kgCO2/kgbCOD and 0.007 kgCO2,eq/kgbCOD, respectively. For an AeD, 3 * 10-10 kgCO2/kgbCOD direct CO2 emissions were measured, while CO2,eq emissions from N2O were 4 * 10-9 kgCO2,eq/kgbCOD. The results for the AS tank and the AeD were used to estimate the net carbon and energy footprint of the entire plant. PMID- 27367526 TI - Raman Spectral and Density Functional Theory Analyses of the CsB3O5 Melt Structure. AB - Melt structures are essential to understand a variety of crystal growth phenomena of alkali-metal triborates, but have not been fully explored. In this work, Raman spectroscopy, coupled with the density functional theory (DFT) method, has been used to solve the CsB3O5 (CBO) melt structure. When the CBO crystal melts, the extra-ring B4-O bonds (the B-O bonds of BO4 groups, O = bridging oxygen atom) that connect two B3O3O4 rings (the basic boron-oxygen unit in the CBO crystal structure) break. As a result, the three-dimensional boron-oxygen network collapses to unique polymer-like [B3O4O2]n chains. On the basis of the optimized [B3O4O2]n chain model, the CBO melt Raman spectrum was calculated by the DFT method for the first time and the calculated results confirm that the [B3O4O2]n chain is the primary species in the CBO melt. These results also demonstrate the capability of the combined Raman spectral and DFT method for analyzing borate melt structures. PMID- 27367527 TI - Acute kidney damage induced by low- and iso-osmolar contrast media in rats: Comparison study with physiologic MRI and histologic-gene examination. AB - PURPOSE: To investigate the physiopathological effects of low- and iso-osmolar contrast media (CM) on renal function with physiologic MRI and histologic-gene examination. MATERIALS AND METHODS: Forty-eight rats underwent time-course DWI and DCE-MRI at 3.0 Tesla (T) before and 5-15 min after exposure of CM or saline (Iop.370: 370 mgI/mL iopromide; Iod.320: 320 mgI/mL iodixanol; Iod.270: 270 mgI/mL iodixanol; 4 gI/kg body weight). Intrarenal viscosity was reflected by apparent diffusion coefficient (ADC). Renal physiologies were evaluated by DCE derived glomerular filtration rate (GFR), renal blood flow (RBF), and renal blood volume (RBV). Potential acute kidney injury (AKI) was determined by histology and the expression of kidney injury molecule 1 (Kim-1). RESULTS: Iop.370 mainly increased ADC in inner-medulla (?ADCIM : 12.3 +/- 11.1%; P < 0.001). Iod.320 and Iod.270 mainly decreased ADC in outer-medulla (?ADCIM ; Iod.320: 16.8 +/- 7.5%; Iod.270: 18.1 +/- 9.5%; P < 0.001) and inner-medulla (?ADCIM ; Iod.320: 28.4 +/- 9.3%; Iod.270: 30.3 +/- 6.3%; P < 0.001). GFR, RBF and RBV were significantly decreased by Iod.320 (?GFR: 45.5 +/- 24.1%; ?RBF: 44.6 +/- 19.0%; ?RBV: 35.2 +/- 10.1%; P < 0.001) and Iod.270 (33.2 +/- 19.0%; 38.1 +/- 15.6%; 30.1 +/- 10.1%; P < 0.001), while rarely changed by Iop.370 and saline. Formation of vacuoles and increase in Kim-1 expression was prominently detected in group of Iod.320, while rarely in Iod.270 and Iop.370. CONCLUSION: Iso-osmolar iodixanol, given at high dose, produced prominent AKI in nonhydrated rats. This renal dysfunction could be assessed noninvasively by physiologic MRI. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:291-302. PMID- 27367529 TI - Back pain and MRI changes in the thoraco-lumbar spine of young elite Mogul skiers. AB - Athletes have a higher prevalence of LBP and spinal abnormalities on Magnetic Resonance Imaging (MRI) compared to non-athletes. The objective of this study was to investigate the amount of spinal MRI abnormalities and the lifetime prevalence of low back pain (LBP) in 16 young elite Mogul skiers compared to 28 non-athletes in the corresponding age in a cross-sectional design. LBP was assessed by a questionnaire consisting of a part regarding previous or present back pain, the Oswestry disability index, and the EuroQol questionnaire. MRI examinations from Th5 to sacrum were conducted to evaluate spinal pathologies. The Mogul skiers had significantly more MRI abnormalities (like disc degeneration) in mean (7.25 vs 3.78, P < 0.023) compared to the controls. No significant difference was seen regarding the lifetime LBP prevalence between the groups (50% vs 42%, P = 0.555). No correlation could be found between disc degeneration and back pain in this study. Young elite Mogul skiers, compared to an age-matched control group of non athletes, have an increased risk of developing spinal abnormalities potentially due to the different high loads that they are subjected to in their sport. Future relationship between the MRI abnormalities and LBP cannot be verified by this study design. PMID- 27367528 TI - Serum Soluble (Pro)Renin Receptor Levels in Maintenance Hemodialysis Patients. AB - The (pro)renin receptor [(P)RR] is cleaved by furin to generate soluble (P)RR [s(P)RR], which reflects the status of the tissue renin-angiotensin system. Hemodialysis patients have advanced atherosclerosis. The aim of this study was to investigate the relationships between serum s(P)RR levels and background factors, including indices of atherosclerosis, in hemodialysis patients. Serum s(P)RR levels were measured in hemodialysis patients and clearance of s(P)RR through the membrane of the dialyzer was examined. Furthermore, relationships between serum s(P)RR levels and background factors were assessed. Serum s(P)RR levels were significantly higher in hemodialysis patients (30.4 +/- 6.1 ng/ml, n = 258) than those in subjects with normal renal function (21.4 +/- 6.2 ng/ml, n = 39, P < 0.0001). Clearance of s(P)RR and creatinine were 56.9 +/- 33.5 and 147.6 +/- 9.50 ml/min, respectively. Serum s(P)RR levels were significantly higher in those with ankle-brachial index (ABI) of < 0.9, an indicator of severe atherosclerosis, than those with ABI of >= 0.9 (32.2 +/- 5.9 and 30.1 +/- 6.2 ng/ml, respectively, P < 0.05). An association between low ABI and high serum s(P)RR levels was observed even after correction for age, history of smoking, HbA1c, and LDL-C. Serum s(P)RR levels were significantly higher in hemodialysis patients when compared with subjects with normal renal function, although s(P)RR is dialyzed to some extent, but to a lesser extent than creatinine. High serum s(P)RR levels may be associated with atherosclerosis independent of other risk factors, suggesting that serum s(P)RR could be used as a marker for atherosclerotic conditions in hemodialysis patients. PMID- 27367530 TI - Endovascular treatment for chronic pulmonary hypertension: a focus on angioplasty for chronic thromboembolic pulmonary hypertension. AB - INTRODUCTION: Percutaneous transluminal pulmonary angioplasty (PTPA) was introduced for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) in the late 20(th) century, and first attempts in collective patients were made in 2001 with beneficial effects but a moderate amount of complications. It was refined around 2010, and has been recently established as an effective and safe treatment. AREAS COVERED: The indication was originally inoperable CTEPH with peripheral lesions, but has now widened to symptomatic or hypoxic patients. The lesion is typically a meshwork-like structure of organized thrombi and is sometimes not seen as a stenosis angiographically, necessitating other means of investigation such as measurement of distal pressure. The technique to treat lesions is the same as for coronary angioplasty except in several ways. Expert commentary: The effects of PTPA are comparable to those of surgical endarterectomy, and the complications of reperfusion pulmonary edema and vascular injury are now controlled by several strategies and based on experience. PMID- 27367531 TI - HIV/AIDS Communication Inequalities and Associated Cognitive and Affective Outcomes: A Call for a Socioecological Approach to AIDS Communication in Sub Saharan Africa. AB - Three-and-a-half decades on, no cure or vaccine is yet on the horizon for HIV, making effective behavior change communication (BCC) the key preventive strategy. Despite considerable success, HIV/AIDS BCC efforts have long been criticized for their primary focus on the individual-level field of influence, drawing on the more reductionist view of causation at the individual level. In view of this, we conducted a series of studies that employed a household survey, field experiment, and textual content analysis, and explored the macro-social-level effects of HIV/AIDS-related media and messages on HIV/AIDS cognitive and affective outcomes in Ethiopia. Against a backdrop of epidemiological and socioecological differences, urban versus rural residence has emerged as an important community level factor that impacts HIV/AIDS-related media and message consumption processes and associated outcomes. The central thread crossing through the six studies included in this paper demonstrates that urban and rural people in high HIV prevalence contexts differ in their concern about and information needs on HIV/AIDS, HIV/AIDS-related media use, and HIV/AIDS-related cognitive and affective outcomes, as well as in their reaction to differently designed/framed HIV prevention messages. This paper proposes that HIV prevention media and message effects in high epidemic situations should be considered from a larger community-level perspective and calls for a socioecological approach to AIDS communication in the hard-hit sub-Saharan Africa. With a number of concrete recommendations to current and future HIV/AIDS BCC efforts in the region, the study joins an emerging body of health communication literature and theorizing that suggests the need to consider media and message effects from a macro-social perspective. PMID- 27367532 TI - Helical Axis Data Visualization and Analysis of the Knee Joint Articulation. AB - We present processing methods and visualization techniques for accurately characterizing and interpreting kinematical data of flexion-extension motion of the knee joint based on helical axes. We make use of the Lie group of rigid body motions and particularly its Lie algebra for a natural representation of motion sequences. This allows to analyze and compute the finite helical axis (FHA) and instantaneous helical axis (IHA) in a unified way without redundant degrees of freedom or singularities. A polynomial fitting based on Legendre polynomials within the Lie algebra is applied to provide a smooth description of a given discrete knee motion sequence which is essential for obtaining stable instantaneous helical axes for further analysis. Moreover, this allows for an efficient overall similarity comparison across several motion sequences in order to differentiate among several cases. Our approach combines a specifically designed patient-specific three-dimensional visualization basing on the processed helical axes information and incorporating computed tomography (CT) scans for an intuitive interpretation of the axes and their geometrical relation with respect to the knee joint anatomy. In addition, in the context of the study of diseases affecting the musculoskeletal articulation, we propose to integrate the above tools into a multiscale framework for exploring related data sets distributed across multiple spatial scales. We demonstrate the utility of our methods, exemplarily processing a collection of motion sequences acquired from experimental data involving several surgery techniques. Our approach enables an accurate analysis, visualization and comparison of knee joint articulation, contributing to the evaluation and diagnosis in medical applications. PMID- 27367533 TI - Refractive Regression and Changes in Central Corneal Thickness Three Years after Laser-Assisted Subepithelial Keratectomy for High Myopia in Eyes with Thin Corneas: A Retrospective Study. AB - This retrospective study aimed to explore refractive regression and central corneal thickness (CCT) following laser-assisted subepithelial keratectomy (LASEK) performed for the correction of high myopia in eyes with thin corneas. Forty patients (19 male, 21 female; mean age, 28.5 years) representing 76 treated eyes were included. The mean optical zone was 6.10 +/- 0.32 mm, and the mean ablation depth was 121.53 +/- 15.48 um. CCT was significantly greater three years after surgery than at three months after surgery (425.66 +/- 15.44 vs. 385.20 +/- 12.81, respectively; p<0.001). The mean change in CCT from three months to three years was 40.46 +/- 14.02 um. The SE at three years was greater than that at three months (p<0.001). Although there was refractive regression, these data suggest that LASEK may have utility in the correction of high myopia in eyes with thin corneas. PMID- 27367534 TI - Microstructures of negative and positive azeotropes. AB - Azeotropes famously impose fundamental restrictions on distillation processes, yet their special thermodynamic properties make them highly desirable for a diverse range of industrial and technological applications. Using neutron diffraction, we investigate the structures of two prototypical azeotropes, the negative acetone-chloroform and the positive benzene-methanol azeotrope. C-HO hydrogen bonding is the dominating interaction in the negative azeotrope but C ClO halogen bonding contributes as well. Hydrogen-bonded chains of methanol molecules, which are on average longer than in pure methanol, are the defining structural feature of the positive azeotrope illustrating the fundamentally different local mixing in the two kinds of azeotropes. The emerging trend for both azeotropes is that the more volatile components experience the more pronounced structural changes in their local environments as the azeotropes form. The mixing of the acetone-chloroform azeotrope is essentially random above 20 A, where the running Kirkwood-Buff integrals of our structural model converge closely to the ones expected from thermodynamic data. The benzene-methanol azeotrope on the other hand displays extended methanol-rich regions and consequently the running Kirkwood-Buff integrals oscillate up to at least 60 A. Our study provides the first experimental insights into the microstructures of azeotropes and a direct link with their thermodynamic properties. Ultimately, this will provide a route for creating tailored molecular environments in azeotropes to improve and fine-tune their performances. PMID- 27367535 TI - Mapping the Trimethoprim-Induced Secondary Metabolome of Burkholderia thailandensis. AB - While bacterial genomes typically contain numerous secondary metabolite biosynthetic gene clusters, only a small fraction of these are expressed at any given time. The remaining majority is inactive or silent, and methods that awaken them would greatly expand our repertoire of bioactive molecules. We recently devised a new approach for identifying inducers of silent gene clusters and proposed that the clinical antibiotic trimethoprim acted as a global activator of secondary metabolism in Burkholderia thailandensis. Herein, we report that trimethoprim triggers the production of over 100 compounds that are not observed under standard growth conditions, thus drastically modulating the secondary metabolic output of B. thailandensis. Using MS/MS networking and NMR, we assign structures to ~40 compounds, including a group of new molecules, which we call acybolins. With methods at hand for activation of silent gene clusters and rapid identification of small molecules, the hidden secondary metabolomes of bacteria can be interrogated. PMID- 27367536 TI - Hepatotoxicity associated with weight loss or sports dietary supplements, including OxyELITE ProTM - United States, 2013. AB - In September 2013, the Hawaii Department of Health (HDOH) was notified of seven adults who developed acute hepatitis after taking OxyELITE ProTM, a weight loss and sports dietary supplement. CDC assisted HDOH with their investigation, then conducted case-finding outside of Hawaii with FDA and the Department of Defense (DoD). We defined cases as acute hepatitis of unknown etiology that occurred from April 1, 2013, through December 5, 2013, following exposure to a weight loss or muscle-building dietary supplement, such as OxyELITE ProTM. We conducted case finding through multiple sources, including data from poison centers (National Poison Data System [NPDS]) and FDA MedWatch. We identified 40 case-patients in 23 states and two military bases with acute hepatitis of unknown etiology and exposure to a weight loss or muscle building dietary supplement. Of 35 case patients who reported their race, 15 (42.9%) reported white and 9 (25.7%) reported Asian. Commonly reported symptoms included jaundice, fatigue, and dark urine. Twenty-five (62.5%) case-patients reported taking OxyELITE ProTM. Of these 25 patients, 17 of 22 (77.3%) with available data were hospitalized and 1 received a liver transplant. NPDS and FDA MedWatch each captured seven (17.5%) case-patients. Improving the ability to search surveillance systems like NPDS and FDA MedWatch for individual and grouped dietary supplements, as well as coordinating case-finding with DoD, may benefit ongoing surveillance efforts and future outbreak responses involving adverse health effects from dietary supplements. This investigation highlights opportunities and challenges in using multiple sources to identify cases of suspected supplement associated adverse events. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. PMID- 27367537 TI - n-3 Fatty acids modulate the mRNA expression of the Nlrp3 inflammasome and Mtor in the liver of rats fed with high-fat or high-fat/fructose diets. AB - CONTEXT: There is evidence that n-3 polyunsaturated fatty acids (n-3-PUFAs) can inhibit mTORC1, which should potentiate autophagy and eliminate NLRP3 inflammasome activity. OBJECTIVE: Evaluate the effect of a high-fat or high fat/fructose diet with and without n-3-PUFAs on hepatic gene expression. MATERIALS AND METHODS: We examined the mRNA expression by RT-PCR of Mtor, Nlrp3, and other 22 genes associated with inflammation in rats livers after a 9-week diet. The dietary regimens were low-fat (control, CD), high-fat (HF), high fat/fructose (HF-Fr), and also each of these supplemented with n-3-PUFAs (CD-n-3 PUFAs, HF-n-3-PUFAs, and HF-Fr-n-3-PUFAs). These data were processed by GeneMania and STRING databases. RESULTS: Compared to the control, the HF group showed a significant increase (between p < 0.05 and p < 0.0001) in 20 of these genes (Il1b, Il18, Rxra, Nlrp3, Casp1, Il33, Tnf, Acaca, Mtor, Eif2s1, Eif2ak4, Nfkb1, Srebf1, Hif1a, Ppara, Ppard, Pparg, Mlxipl, Fasn y Scd1), and a decrease in Sirt1 (p < 0.05). With the HF-Fr diet, a significant increase (between p < 0.05 and p < 0.005) was also found in the expression of 16 evaluated genes (Srebf1, Mlxipl, Rxra, Abca1, Il33, Nfkb1, Hif1a, Pparg, Casp1, Il1b, Il-18, Tnf, Ppard, Acaca, Fasn, Scd1), along with a decrease in the transcription of Mtor and Elovl6 (p < 0.05). Contrarily, many of the genes whose expression increased with the HF and HF-Fr diets did not significantly increase with the HF-n-3-PUFAs or HF-Fr-n-3 PUFAs diet. DISCUSSION AND CONCLUSION: We found the interrelation of the genes for the mTORC1 complex, the NLRP3 inflammasome, and other metabolically important proteins, and that these genes respond to n-3-PUFAs. PMID- 27367539 TI - Expression of Concern. PMID- 27367538 TI - Pelvic Angiography for Trauma in Children: A Rare but Useful Adjunct. AB - Introduction Pelvic angiography with embolization can successfully control hemorrhage in adults with pelvic fractures. However, evidence to support similar application in children is sparse. We describe our experience using angiography for pediatric pelvic fractures to further highlight the safety and efficacy of this treatment approach. Methods A retrospective review at a pediatric tertiary care center was performed from 2004 to 2014. Inpatients treated for a pelvic fracture were considered. Results A total of 216 patients were analyzed. Four patients (1.9%) underwent pelvic angiography. Three of these patients had active contrast extravasation on angiography and underwent successful embolization. All patients who underwent angiography showed computed tomography (CT) or clinical evidence of ongoing hemorrhage. No surgical intervention was needed after angiography. No complications of angiography occurred. Three patients who were found to have active extravasation on CT did not require angiography and were stabilized in the intensive care unit; two patients went on to have delayed operative repair. Mortality was 2.3%. All deaths were secondary to concomitant traumatic brain injury. No mortality occurred in patients undergoing pelvic angiography or those with pelvic contrast extravasation on CT. Conclusions Pelvic angiography is a useful treatment option in pediatric patients with pelvic fractures and clinical evidence of ongoing blood loss without other explanation. Contrast extravasation on CT scan alone may not require further intervention. PMID- 27367541 TI - Collective Signal Processing in Cluster Chemotaxis: Roles of Adaptation, Amplification, and Co-attraction in Collective Guidance. AB - Single eukaryotic cells commonly sense and follow chemical gradients, performing chemotaxis. Recent experiments and theories, however, show that even when single cells do not chemotax, clusters of cells may, if their interactions are regulated by the chemoattractant. We study this general mechanism of "collective guidance" computationally with models that integrate stochastic dynamics for individual cells with biochemical reactions within the cells, and diffusion of chemical signals between the cells. We show that if clusters of cells use the well-known local excitation, global inhibition (LEGI) mechanism to sense chemoattractant gradients, the speed of the cell cluster becomes non-monotonic in the cluster's size-clusters either larger or smaller than an optimal size will have lower speed. We argue that the cell cluster speed is a crucial readout of how the cluster processes chemotactic signals; both amplification and adaptation will alter the behavior of cluster speed as a function of size. We also show that, contrary to the assumptions of earlier theories, collective guidance does not require persistent cell-cell contacts and strong short range adhesion. If cell cell adhesion is absent, and the cluster cohesion is instead provided by a co attraction mechanism, e.g. chemotaxis toward a secreted molecule, collective guidance may still function. However, new behaviors, such as cluster rotation, may also appear in this case. Co-attraction and adaptation allow for collective guidance that is robust to varying chemoattractant concentrations while not requiring strong cell-cell adhesion. PMID- 27367542 TI - Validity and Reliability of a Self-Reported Measure of Antihypertensive Medication Adherence in Uganda. AB - BACKGROUND: The Morisky Medication Adherence scale (MMAS-8) is a widely used self reported measure of adherence to antihypertensive medications that has not been validated in hypertensive patients in sub-Saharan Africa. METHODS: We carried out a cross-sectional study to examine psychometric properties of a translated MMAS-8 (MMAS-U) in a tertiary care hypertension clinic in Uganda. We administered the MMAS-U to consecutively selected hypertensive adults and used principal factor analysis and Cronbach's alpha to determine its validity and internal consistency respectively. Then we randomly selected one-sixth of participants for a 2-week test-retest telephone interview. Lastly, we used ordinal logistic regression modeling to explore factors associated with levels of medication adherence. RESULTS: Of the 329 participants, 228 (69%) were females, median age of 55 years [Interquartile range (IQR) (46-66)], and median duration of hypertension of 4 years [IQR (2-8)]. The adherence levels were low (MMAS-U score <= 5) in 85%, moderate (MMAS-U score 6-7) in 12% and high (MMAS-U score >=8) in 3%. The factor analysis of construct validity was good (overall Kaiser's measure of sampling adequacy for residuals of 0.72) and identified unidimensionality of MMAS-U. The internal consistency of MMAS-U was moderate (Cronbach alpha = 0.65), and test retest reliability was low (weighted kappa = 0.36; 95% CI -0.01, 0.73). Age of 40 years or greater was associated with low medication adherence (p = 0.02) whereas a family member buying medication for participants (p = 0.02) and purchasing medication from a private clinic (p = 0.02) were associated with high adherence. CONCLUSION: The Ugandan version of the MMAS-8 (MMAS-U) is a valid and reliable measure of adherence to antihypertensive medication among Ugandan outpatients receiving care at a public tertiary facility. Though the limited supply of medication affected adherence, this easy to use tool can be adapted to assess medication adherence among adults with hypertension in Uganda. PMID- 27367543 TI - Novel Disease-Drug Database Demonstrating Applicability for Pharmacogenomic-Based Prescribing. AB - Significant advances have been made in the clinical implementation of pharmacogenomics in recent years with tools for clinical decision support (CDS) being developed and integrated in the electronic health record (EHR). In this issue, the article by Hussain et al. describes the creation of a disease-drug association tool that enables providers to search by disease indications to receive a list of treatment options marked with pharmacogenomics annotations at the point of prescribing. PMID- 27367544 TI - The Ssr protein (T1E_1405) from Pseudomonas putida DOT-T1E enables oligonucleotide-based recombineering in platform strain P. putida EM42. AB - Some strains of the soil bacterium Pseudomonas putida have become in recent years platforms of choice for hosting biotransformations of industrial interest. Despite availability of many genetic tools for this microorganism, genomic editing of the cell factory P. putida EM42 (a derivative of reference strain KT2440) is still a time-consuming endeavor. In this work we have investigated the in vivo activity of the Ssr protein encoded by the open reading frame T1E_1405 from Pseudomonas putida DOT-T1E, a plausible functional homologue of the beta protein of the Red recombination system of lambda phage of Escherichia coli. A test based on the phenotypes of pyrF mutants of P. putida (the yeast's URA3 ortholog) was developed for quantifying the ability of Ssr to promote invasion of the genomic DNA replication fork by synthetic oligonucleotides. The efficiency of the process was measured by monitoring the inheritance of the changes entered into pyrF by oligonucleotides bearing mutated sequences. Ssr fostered short and long genomic deletions/insertions at considerable frequencies as well as single base swaps not affected by mismatch repair. These results not only demonstrate the feasibility of recombineering in P. putida, but they also enable a suite of multiplexed genomic manipulations in this biotechnologically important bacterium. PMID- 27367546 TI - Predominance of enterovirus B and echovirus 30 as cause of viral meningitis in a UK population. AB - BACKGROUND/OBJECTIVES: Enteroviruses are the most common cause of aseptic or lymphocytic meningitis, particularly in children. With reports of unusually severe neurological disease in some patients infected with enterovirus D68 in North America, and a recent increase in the number of paediatric enterovirus meningitis cases presenting in this UK Midlands population, a retrospective regional surveillance study was performed. STUDY DESIGN: Cerebrospinal fluid (CSF) samples received were tested using the polymerase chain reaction (PCR) for HSV-1/2, VZV, enteroviruses and parechoviruses. Enterovirus PCR positive CSF samples were sent for further serotyping. A phylogenetic tree was constructed of the echovirus 30 VP1 sequences, where sufficient sample remained for sequencing. RESULTS: The number of enterovirus positive CSFs from each year were: 21 (2008), 7 (2011), 53 (2012), 58 (2013) and 31 (2014). Overall, 163 of the 170 serotyped enteroviruses belonged to the species B (echovirus 5, 6, 7, 9, 11, 13, 16, 17, 18, 21, 25, 30; coxsackie B1, B2, B3, B4, B5, A9), with only 7 belonging to species A (coxsackie A2, A6, A16 and enterovirus 71). Echovirus 30 was the predominant serotype overall, identified in 43 (25.3%) of samples, with a significantly higher proportion in the adult age group (37.3%) compared to the infant age group (12.3%). Phylogenetic analysis showed that these UK Midlands echovirus 30 VP1 sequences clustered most closely with those from Europe and China. CONCLUSION: This study showed a continued predominance of echovirus 30 as a cause of viral meningitis, particularly in adults, though more surveillance is needed. PMID- 27367545 TI - New findings in HCV genotype distribution in selected West European, Russian and Israeli regions. AB - BACKGROUND: HCV affects 185 million people worldwide and leads to death and morbidities. HCV has a high genetic diversity and is classified into seven genotypes and 67 subtypes. Novel anti-HCV drugs (Direct-Acting-Antivirals) eligibility, resistance and cure rates depend on HCV geno/subtype (GT). OBJECTIVES: Analysis of epidemiological information and viral GT from patients undergoing viral genotyping in 2011-2015. STUDY DESIGN: Anonymized information from 52 centers was analyzed retrospectively. RESULTS: 37,839 samples were included in the study. We show that the GT distribution is similar throughout Western European countries, with some local differences. Here GTs 1 and 2 prevalences are lower and of GT4 higher than in all previous reports. Israel has a unique GT pattern and in South Russia the GT proportions are more similar to Asia. GTs 5 and 6 were detected in very low proportions. Three cases of the recombinant genotype P were reported in Munich (Germany). In addition, we observed that GT proportion was dependant on patients gender, age and transmission route: GTs 1b and 2 were significantly more common in female, older, nosocomially-infected patients, while GTs 1a, 3 and 4 were more frequent in male, younger patients infected by tattooing, drug consume, and/or sexual practices. In infections acquired by drug consume, GTs 1a (35.0%) and 3 (28.1%) prevailed. In infections related to sexual practices lower proportion of GT3 (14.0%) and higher of GT4 (20.2%) were detected. GT4 was mostly abundant in MSM (29.6%). HIV coinfection was significantly associated with higher proportions GTs 1a and 4 (42.5% and 19.3%, respectively). CONCLUSION: Genotype prevalence evolves and correlates to epidemiological factors. Continuous surveillance is necessary to better assess hepatitis C infection in Europe and to take appropriate actions. PMID- 27367548 TI - Single actuator wave-like robot (SAW): design, modeling, and experiments. AB - In this paper, we present a single actuator wave-like robot, a novel bioinspired robot which can move forward or backward by producing a continuously advancing wave. The robot has a unique minimalistic mechanical design and produces an advancing sine wave, with a large amplitude, using only a single motor but with no internal straight spine. Over horizontal surfaces, the robot does not slide relative to the surface and its direction of locomotion is determined by the direction of rotation of the motor. We developed a kinematic model of the robot that accounts for the two-dimensional mechanics of motion and yields the speed of the links relative to the motor. Based on the optimization of the kinematic model, and accounting for the mechanical constraints, we have designed and built multiple versions of the robot with different sizes and experimentally tested them (see movie). The experimental results were within a few percentages of the expectations. The larger version attained a top speed of 57 cm s(-1) over a horizontal surface and is capable of climbing vertically when placed between two walls. By optimizing the parameters, we succeeded in making the robot travel by 13% faster than its own wave speed. PMID- 27367547 TI - Quality of End-of-Life Care Provided to Patients With Different Serious Illnesses. AB - IMPORTANCE: Efforts to improve end-of-life care have focused primarily on patients with cancer. High-quality end-of-life care is also critical for patients with other illnesses. OBJECTIVE: To compare patterns of end-of-life care and family-rated quality of care for patients dying with different serious illnesses. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cross-sectional study was conducted in all 146 inpatient facilities within the Veteran Affairs health system among patients who died in inpatient facilities between October 1, 2009, and September 30, 2012, with clinical diagnoses categorized as end-stage renal disease (ESRD), cancer, cardiopulmonary failure (congestive heart failure or chronic obstructive pulmonary disease), dementia, frailty, or other conditions. Data analysis was conducted from April 1, 2014, to February 10, 2016. MAIN OUTCOMES AND MEASURES: Palliative care consultations, do-not-resuscitate orders, death in inpatient hospices, death in the intensive care unit, and family reported quality of end-of-life care. RESULTS: Among 57 753 decedents, approximately half of the patients with ESRD, cardiopulmonary failure, or frailty received palliative care consultations (adjusted proportions, 50.4%, 46.7%, and 43.7%, respectively) vs 73.5% of patients with cancer and 61.4% of patients with dementia (P < .001). Approximately one-third of patients with ESRD, cardiopulmonary failure, or frailty (adjusted proportions, 32.3%, 34.1%, and 35.2%, respectively) died in the intensive care unit, more than double the rates among patients with cancer and those with dementia (13.4% and 8.9%, respectively) (P < .001). Rates of excellent quality of end-of-life care reported by 34 005 decedents' families were similar for patients with cancer and those with dementia (adjusted proportions, 59.2% and 59.3%; P = .61), but lower for patients with ESRD, cardiopulmonary failure, or frailty (54.8%, 54.8%, and 53.7%, respectively; all P <= .02 vs patients with cancer). This quality advantage was mediated by palliative care consultation, setting of death, and a code status of do-not resuscitate; adjustment for these variables rendered the association between diagnosis and overall end-of-life care quality nonsignificant. CONCLUSIONS AND RELEVANCE: Family-reported quality of end-of-life care was significantly better for patients with cancer and those with dementia than for patients with ESRD, cardiopulmonary failure, or frailty, largely owing to higher rates of palliative care consultation and do-not-resuscitate orders and fewer deaths in the intensive care unit among patients with cancer and those with dementia. Increasing access to palliative care and goals of care discussions that address code status and preferred setting of death, particularly for patients with end-organ failure and frailty, may improve the overall quality of end-of-life care for Americans dying of these illnesses. PMID- 27367549 TI - To Appear in CHEMICAL REVIEWS, Vol. 99, No. 7. PMID- 27367550 TI - Patient and Physician Attitudes Toward Low-Value Diagnostic Tests. PMID- 27367551 TI - The safety of pharmacologic options for the treatment of persons with hemophilia. AB - INTRODUCTION: The mainstay of treatment of hemophilia A and B is the replacement of the congenitally deficient coagulation factor through the intravenous infusion of specific concentrates (factor VIII, FVIII, in hemophilia A; factor IX, FIX, in hemophilia B). Several commercial brands of FVIII or FIX products extracted from human plasma or engineered using recombinant DNA technology are available. AREAS COVERED: We analyze the safety aspects of plasma-derived and recombinant FVIII and FIX products licensed in Europe, focusing on their pathogen safety and inhibitor and thrombosis risks. The safety aspects of bypassing agents (i.e., activated prothrombin complex concentrates and recombinant activated factor VII) used for treatment of bleeding episodes in inhibitor patients will be also briefly discussed. EXPERT OPINION: The analysis of the published literature documents the high degree of safety from pathogen risk for both plasma-derived and recombinant products available for hemophilia treatment. The main threat to factor concentrate safety is represented by the development of neutralizing alloantibodies against the infused coagulation factor, which in hemophilia A seem to occur more frequently following the administration of recombinant than plasma derived FVIII products. Great expectations are placed on newer products, particularly on those based upon mechanisms of action other than FVIII replacement. PMID- 27367552 TI - Red Meat and Processed Meat Consumption and Nasopharyngeal Carcinoma Risk: A Dose response Meta-analysis of Observational Studies. AB - The purpose of this study is to clarify and quantify the potential dose-response association between the intake of total red and total processed meat and risk of nasopharyngeal carcinoma (NPC). Relevant studies were identified by searching PubMed, EMBASE, and Chinese databases (CNKI and Wanfang). The summary relative risk (RR) with 95% confidence interval (95%CI) was calculated. A total of 15 independent studies with 12,735 subjects were identified. Compared with the low rank intake, the summary RR of NPC was 1.35 (95%CI, 1.21-1.51) for total red meat and 1.46 (95%CI, 1.34-1.64) for total processed meat. For the moderate-rank intake, the summary RR of NPC was 1.54 (95%CI, 1.36-1.79) for total red meat and 1.59 (95%CI, 1.3-1.90) for total processed meat. The summary RR for high-rank intake was 1.71 (95%CI, 1.14-2.55) for total red meat and 2.11 (95%CI, 1.31-3.42) for total processed meat. The combined estimates showed obvious evidence of statistically significant association between total red and total processed meat consumption dose and risk of NPC (Ptrend< 0.01). In conclusion, our data suggest that a high intake of total red or total processed meat is associated with a significantly increased risk of NPC. PMID- 27367554 TI - Evaluation and lessons learned from an undergraduate service learning course providing youth-focused relationship education. AB - Adolescent romantic relationships are known to have a significant impact on individual well-being and development. However, few teens experience formal education about the knowledge and skills necessary for building healthy romantic relationships. In response, a statewide relationship education initiative was developed at a large university in a Southeastern state. Undergraduates who enrolled in a service learning course in Human Development and Family Studies partnered with this initiative and implemented a relationship education program targeting high school students. A service learning model is used in this initiative because it offers opportunities for students' professional development and experiential learning. The present article provides a formative and illustrative summative evaluation of the service learning program. Specifically, the primary aims of this paper are to 1) provide an overview of the service learning course components; 2) describe preparation of the service learning students and their implementation of the relationship education program; 3) discuss challenges and lessons learned; and 4) offer initial evidence of effectiveness by showing change in targeted outcomes for the high school student recipients of the relationship education program. PMID- 27367555 TI - Excellence in Medicine and the Case for Aspirational Ethics. PMID- 27367556 TI - bioassayR: Cross-Target Analysis of Small Molecule Bioactivity. AB - Despite a large and rapidly growing body of small molecule bioactivity screens available in the public domain, systematic leverage of the data to assess target druggability and compound selectivity has been confounded by a lack of suitable cross-target analysis software. We have developed bioassayR, a computational tool that enables simultaneous analysis of thousands of bioassay experiments performed over a diverse set of compounds and biological targets. Unique features include support for large-scale cross-target analyses of both public and custom bioassays, generation of high throughput screening fingerprints (HTSFPs), and an optional preloaded database that provides access to a substantial portion of publicly available bioactivity data. bioassayR is implemented as an open-source R/Bioconductor package available from https://bioconductor.org/packages/bioassayR/ . PMID- 27367557 TI - 5-(N, N-Hexamethylene) amiloride is a GABA-A rho1 receptor positive allosteric modulator. AB - Guanidine compounds act as ion channel modulators. In the case of Cys-loop receptors, the guanidine compound amiloride antagonized the heteromeric GABA-A, glycine, and nicotinic acetylcholine receptors. However, amiloride exhibits characteristics consistent with a positive allosteric modulator for the human GABA-A (hGABA-A) rho1 receptor. Site-directed mutagenesis revealed that the positive allosteric modulation was influenced by the GABA-A rho1 second transmembrane domain 15' position, a site implicated in ligand allosteric modulation of Cys-loop receptors. There are a variety of amiloride derivatives that provide opportunities to assess the significance of amiloride functional groups (e.g., the guanidine group, the pyrazine ring, etc.) in the modulation of the GABA-A rho1 receptor activity. We utilized 3 amiloride derivatives (benzamil, phenamil, and 5-(N, N-Hexamethylene) amiloride) to assess the contribution of these groups toward the potentiation of the GABA-A rho1 receptor. Benzamil and phenamil failed to potentiate on the wild type GABA-A rho1 GABA-mediated current while HMA demonstrated efficacy only at the highest concentration studied. The hGABA-A rho1 (I15'N) mutant receptor activity was potentiated by lower HMA concentrations compared to the wild type receptor. Our findings suggest that an exposed guanidine group on amiloride and amiloride derivatives is critical for modulating the GABA-A rho1 receptor. The present study provides a conceptual framework for predicting which amiloride derivatives will demonstrate positive allosteric modulation of the GABA-A rho1 receptor. PMID- 27367558 TI - Immune checkpoint blockade - a treatment for urological cancers? PMID- 27367559 TI - Association of Religious Involvement and Suicide. PMID- 27367560 TI - The Sonographic Appearance of Ectopic Pregnancy After Treatment With Methotrexate. PMID- 27367562 TI - Cofacial Organic Click Cage to Intercalate Polycyclic Aromatic Hydrocarbons. AB - The synthesis of a 3-fold symmetric cofacial organic cage (COC) through Cu(I) catalyzed azide-alkyne cycloaddition is reported. The COC can function as an efficient receptor for carcinogenic polycyclic aromatic hydrocarbons to intercalate them in its intrinsic cavity through donor-acceptor and pi...pi stacking interactions. The association constants (Ka) are in the range of 3.7 * 10(4) to 1.3 * 10(6) M(-1). X-ray diffraction analysis authenticated that the polycyclic aromatic hydrocarbons (PAHs) are intercalated in the interior of the COC. PMID- 27367561 TI - The hot body issue: Weight and caption tone in celebrity gossip magazines. AB - While representations of bodies and weight have been studied in regards to fashion and fitness magazines, little research exists that examines such representations in celebrity gossip magazines. Using data collected through content analysis of 262 photo-caption units published in June 2015 issues of American celebrity gossip magazines, this study examines representations of bodies within the genre and the relationship between the gender, race, and body size of pictured celebrities and the tone of accompanying captions. Results indicate that celebrity gossip magazines critique the bodies of both female and male subjects, but that women are more likely to be the subject of negative comments than men. Underweight women and overweight men are especially targeted for criticism. Latinos are praised more often than other racial groups. The implications of these representations are discussed. PMID- 27367563 TI - The differences between sex offenders who victimise older women and sex offenders who offend against children. AB - OBJECTIVES: Within the literature on sex offending, much attention is paid to the distinction between those sex offenders who offend against adults and those who offend against children. In contrast, there is a paucity of research into sex offenders who offend specifically against elderly or older victims. METHOD: A detailed interview and psychometric tests were conducted with a sample of 28 sex offenders who had been convicted of a sexually motivated offence against an older female. These data were compared to a sample of 23 child sex offenders. RESULTS: Results indicate that amongst other significant differences between these sub groups, men who offend against older women are generally younger, are more violent, and are more likely to use a weapon and cause injury and death compared to child sex offenders. The men who offended against children were more likely to think about and plan their offending, spend more time with the victim pre and post offence, admit sexual arousal during the offence, and admit to a sexual motivation for the offence. CONCLUSIONS: This study suggests that men who sexually offend against older women and men who sexually offend against children are distinct groups. Treatment and risk management strategies should take this into account. Further exploration of this sub-group of offenders is recommended to help inform treatment and risk management strategies for sex offenders who offend against older people. PMID- 27367564 TI - PTBP1 modulation of MCL1 expression regulates cellular apoptosis induced by antitubulin chemotherapeutics. AB - Myeloid cell leukemia sequence 1 (MCL1), an anti-apoptotic BCL2 family protein, is a key regulator of intrinsic apoptosis. Normal cells require strict control over MCL1 expression with aberrant MCL1 expression linked to the emergence of various diseases and chemoresistance. Previous studies have detailed how MCL1 expression is regulated by multiple mechanisms both transcriptionally and translationally. However, characterization of the post-transcriptional regulators of MCL1 mRNA is limited. Polypyrimidine tract binding protein 1 (PTBP1) is a known regulator of post-transcriptional gene expression that can control mRNA splicing, translation, stability and localization. Here we demonstrate that PTBP1 binds to MCL1 mRNA and that knockdown of PTBP1 upregulates MCL1 expression in cancer cells by stabilizing MCL1 mRNA and increasing MCL1 mRNA accumulation in cytoplasm. Further, we show that depletion of PTBP1 protects cancer cells from antitubulin agent-induced apoptosis in a MCL1-dependent manner. Taken together, our findings suggest that PTBP1 is a novel regulator of MCL1 mRNA by which it controls apoptotic response to antitubulin chemotherapeutics. PMID- 27367567 TI - Signalling changes to individuals who show resistance to change can reduce challenging behaviour. AB - BACKGROUND & OBJECTIVES: Several neurodevelopmental disorders are associated with resistance to change and challenging behaviours - including temper outbursts - that ensue following changes to routines, plans or expectations (here, collectively: expectations). Here, a change signalling intervention was tested for proof of concept and potential practical effectiveness. METHODS: Twelve individuals with Prader-Willi syndrome participated in researcher- and caregiver led pairing of a distinctive visual-verbal signal with subsequent changes to expectations. Specific expectations for a planned subset of five participants were systematically observed in minimally manipulated natural environments. Nine caregivers completed a temper outburst diary during a four week baseline period and a two week signalling evaluation period. RESULTS: Participants demonstrated consistently less temper outburst behaviour in the systematic observations when changes imposed to expectations were signalled, compared to when changes were not signalled. Four of the nine participants whose caregivers completed the behaviour diary demonstrated reliable reductions in temper outbursts between baseline and signalling evaluation. LIMITATIONS: An active control group for the present initial evaluation of the signalling strategy using evidence from caregiver behaviour diaries was outside the scope of the present pilot study. Thus, findings cannot support the clinical efficacy of the present signalling approach. CONCLUSIONS: Proof of concept evidence that reliable pairing of a distinctive cue with a subsequent change to expectation can reduce associated challenging behaviour is provided. Data provide additional support for the importance of specific practical steps in further evaluations of the change signalling approach. PMID- 27367565 TI - The apoptotic members CD95, BclxL, and Bcl-2 cooperate to promote cell migration by inducing Ca(2+) flux from the endoplasmic reticulum to mitochondria. AB - Metalloprotease-processed CD95L (cl-CD95L) is a soluble cytokine that implements a PI3K/Ca(2+) signaling pathway in triple-negative breast cancer (TNBC) cells. Accordingly, high levels of cl-CD95L in TNBC women correlate with poor prognosis, and administration of this ligand in an orthotopic xenograft mouse model accelerates the metastatic dissemination of TNBC cells. The molecular mechanism underlying CD95-mediated cell migration remains unknown. Here, we present genetic and pharmacologic evidence that the anti-apoptotic molecules BclxL and Bcl-2 and the pro-apoptotic factors BAD and BID cooperate to promote migration of TNBC cells stimulated with cl-CD95L. BclxL was distributed in both endoplasmic reticulum (ER) and mitochondrion membranes. The mitochondrion-localized isoform promoted cell migration by interacting with voltage-dependent anion channel 1 to orchestrate Ca(2+) transfer from the ER to mitochondria in a BH3-dependent manner. Mitochondrial Ca(2+) uniporter contributed to this flux, which favored ATP production and cell migration. In conclusion, this study reveals a novel molecular mechanism controlled by BclxL to promote cancer cell migration and supports the use of BH3 mimetics as therapeutic options not only to kill tumor cells but also to prevent metastatic dissemination in TNBCs. PMID- 27367566 TI - Cacidases: caspases can cleave after aspartate, glutamate and phosphoserine residues. AB - Caspases are a family of proteases found in all metazoans, including a dozen in humans, that drive the terminal stages of apoptosis as well as other cellular remodeling and inflammatory events. Caspases are named because they are cysteine class enzymes shown to cleave after aspartate residues. In the past decade, we and others have developed unbiased proteomic methods that collectively identified ~2000 native proteins cleaved during apoptosis after the signature aspartate residues. Here, we explore non-aspartate cleavage events and identify 100s of substrates cleaved after glutamate in both human and murine apoptotic samples. The extended consensus sequence patterns are virtually identical for the aspartate and glutamate cleavage sites suggesting they are cleaved by the same caspases. Detailed kinetic analyses of the dominant apoptotic executioner caspases-3 and -7 show that synthetic substrates containing DEVD? are cleaved only twofold faster than DEVE?, which is well within the 500-fold range of rates that natural proteins are cut. X-ray crystallography studies confirm that the two acidic substrates bind in virtually the same way to either caspases-3 or -7 with minimal adjustments to accommodate the larger glutamate. Lastly, during apoptosis we found 121 proteins cleaved after serine residues that have been previously annotated to be phosphorylation sites. We found that caspase-3, but not caspase 7, can cleave peptides containing DEVpS? at only threefold slower rate than DEVD?, but does not cleave the unphosphorylated serine peptide. There are only a handful of previously reported examples of proteins cleaved after glutamate and none after phosphorserine. Our studies reveal a much greater promiscuity for cleaving after acidic residues and the name 'cacidase' could aptly reflect this broader specificity. PMID- 27367568 TI - Parametric Response Mapping of Bronchiolitis Obliterans Syndrome Progression After Lung Transplantation. AB - Bronchiolitis obliterans syndrome (BOS) remains a major complication after lung transplantation. Air trapping and mosaic attenuation are typical radiological features of BOS; however, quantitative evaluation remains troublesome. We evaluated parametric response mapping (PRM, voxel-to-voxel comparison of inspiratory and expiratory computed tomography [CT] scans) in lung transplant recipients diagnosed with BOS (n = 20) and time-matched stable lung transplant recipients (n = 20). Serial PRM measurements were performed prediagnosis, at time of BOS diagnosis, and postdiagnosis (Tpre , T0 , and Tpost , respectively), or at a postoperatively matched time in stable patients. PRM results were correlated with pulmonary function and confirmed by microCT analysis of end-stage explanted lung tissue. Using PRM, we observed an increase in functional small airway disease (fSAD), from Tpre to T0 (p = 0.006) and a concurrent decrease in healthy parenchyma (p = 0.02) in the BOS group. This change in PRM continued to Tpost , which was significantly different compared to the stable patients (p = 0.0002). At BOS diagnosis, the increase in fSAD was strongly associated with a decrease in forced expiratory volume in 1 s (p = 0.011). Micro-CT confirmed the presence of airway obliteration in a sample of a BOS patient identified with 67% fSAD by PRM. We demonstrated the use of PRM as an adequate output to monitor BOS progression in lung transplant recipients. PMID- 27367569 TI - Therapeutic effects of 10-HzPulsed wave lasers in rat depression model: A comparison between near-infrared and red wavelengths. AB - BACKGROUND AND OBJECTIVE: The application of transcranial low-level light/laser therapy (tLLLT) in the range of red to near-infrared (NIR) spectrum for psychological disorders is a new area that is attracting growing interest in recent years. The photomodulation effects of NIR and red coherent lights on the activity of cytochrome c oxidase in neuronal cells of brain have been recently introduced. This study, therefore, sought to compare the therapeutic effects of 10-Hz pulsed wave NIR (810 nm) laser with red (630 nm) laser using the same delivered energy density and Citalopram in rat chronic mild stress (CMS) model of depression and anxiety. MATERIALS AND METHODS: CMS procedures (for 4 weeks) were used to induce stress. GaAlAs diode laser with red and NIR wavelengths on 10-Hz pulsed wave (50% duty cycle) were used to perform tLLLT treatment for three weeks. An energy density of about 1.2 J/cm-(2) per each session was delivered through a light spot with a diameter of 3-mm to the prefrontal cortex for both wavelengths. Citalopram (10 mg/kg, Intraperitoneal) was administered for twenty one consecutive days to the drug group. RESULTS: The findings of the present study showed an increase in swimming and decrease in immobility time, for both NIR laser and Citalopram groups compared to the stress group in forced swimming test. Anxiety-like behaviors showed insignificant decrease in all treatment groups in elevated plus maze test. The induction of stress significantly increased serum cortisol levels and treatments with both red laser and Citalopram decreased it. Hyperglycemia induced by CMS returned to normal levels in all treatment groups. The assessment of body weight also showed a significant increase in NIR laser group compared to the stress group by the end of the experiment. CONCLUSIONS: This study showed that non-invasive tLLLT using 10-Hz pulsed NIR laser light was as effective as Citalopram and more effective than red laser in the treatment of depressive-like behaviors and may help improve tLLLT as an alternative non-pharmacological treatments of psychological disorders such as depression. Lasers Surg. Med. 48:695-705, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27367570 TI - Prescription of Brand-Name Medications When Generic Alternatives Are Available Patently Unfair. PMID- 27367571 TI - Atypical epithelial hyperplasia of the breast: state of the art. AB - INTRODUCTION: Atypical epithelial hyperplasia (AEH) of the breast is considered benign histological lesions with breast cancer risk. This review focuses on clinical signification and management of AEH that remains controversial. AREAS COVERED: A review of published studies was performed using medline database. In this review, we fully describe the current evidence available. In particular, we describe 1) data from immunohistochemistry and molecular studies that suggest AEH is a precursor of breast cancer; 2) epidemiological studies demonstrate low rate of breast cancer in women with AEH; 3) surgical excision is necessary after diagnosis of AEH, such as lobular carcinoma in situ or atypical ductal hyperplasia, on core needle biopsy; 4) although current recommendations are evolving to fewer (if not no) excisions for flat epithelial with atypia and classic lobular neoplasia found on percutaneous biopsy (without radiologic indications for excision). Expert commentary: HEA management steel need prospective evidences, but recent retrospective data give some clue for less invasive management for some of HEA. PMID- 27367572 TI - Computed Tomography Perfusion and Diffusion-Weighted Imaging in Patients With Acute Stroke. PMID- 27367574 TI - Running related gluteus medius function in health and injury: A systematic review with meta-analysis. AB - Running is a popular sport and recreational physical activity worldwide. Musculoskeletal injuries in runners are common and may be attributed to the inability to control pelvic equilibrium in the coronal plane. This lack of pelvic control in the frontal plane can stem from dysfunction of the gluteus medius. The aim of this systematic review was therefore to: (i) compile evidence of the activity profile of gluteus medius when running; (ii) identify how gluteus medius activity (electromyography) varies with speed, cadence and gender when running; (iii) compare gluteus medius activity in injured runners to matched controls. Seven electronic databases were searched from their earliest date until March 2015. Thirteen studies met our eligibility criteria. The activity profile was mono-phasic with a peak during initial loading (four studies). Gluteus medius amplitude increases with running speed; this is most evident in females. The muscles' activity has been recorded in injured runners with Achilles tendinopathy (two studies) and patellofemoral pain syndrome (three studies). The strongest evidence indicates a moderate and significant reduction in gluteus medius duration of activity when running in people with patellofemoral pain syndrome. This dysfunction can potentially be mediated with running retraining strategies. PMID- 27367573 TI - Combined treatment with a beta3 -adrenergic receptor agonist and a muscarinic receptor antagonist inhibits detrusor overactivity induced by cold stress in spontaneously hypertensive rats. AB - AIMS: This study determined if combined treatment with the muscarinic receptor (MR) antagonist solifenacin and the beta3 -adrenergic receptor (AR) agonist mirabegron could inhibit detrusor overactivity induced by cold stress in spontaneously hypertensive rats (SHRs). METHODS: Thirty-two female 10-week-old SHRs were fed an 8% NaCl-supplemented diet for 4 weeks. Cystometric measurements of the unanesthetized, unrestricted rats were performed at room temperature (RT, 27 +/- 2 degrees C) for 20 min. The rats were then intravenously administered vehicle, 0.1 mg/kg solifenacin alone, 0.1 mg/kg mirabegron alone, or the combination of 0.1 mg/kg mirabegron and 0.1 mg/kg solifenacin (n = 8 each group). Five minutes later, the treated rats were exposed to low temperature (LT, 4 +/- 2 degrees C) for 40 min. Finally, the rats were returned to RT. After the cystometric investigations, the beta3 -ARs and M3 -MRs expressed within the urinary bladders were analyzed. RESULTS: Just after transfer from RT to LT, vehicle-, solifenacin-, and mirabegron-treated SHRs exhibited detrusor overactivity that significantly decreased voiding interval and bladder capacity. However, treatment with the combination of solifenacin and mirabegron partially inhibited the cold stress-induced detrusor overactivity patterns. The decreases of voiding interval and bladder capacity in the combination-treated rats were significantly inhibited compared to other groups. Within the urinary bladders, there were no differences between expression levels of M3 -MR and beta3 -AR mRNA. The tissue distribution of M3 -MRs was similar to that of the beta3 -ARs. CONCLUSIONS: This study suggested that the combination of solifenacin and mirabegron act synergistically to inhibit the cold stress-induced detrusor overactivity in SHRs. Neurourol. Urodynam. 36:1026-1033, 2017. (c) 2016 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc. PMID- 27367575 TI - Cyanide Suicide After Deep Web Shopping: A Case Report. AB - Cyanide is a product that is known for its use in industrial or laboratory processes, as well as for intentional intoxication. The toxicity of cyanide is well described in humans with rapid inhibition of cellular aerobic metabolism after ingestion or inhalation, leading to severe clinical effects that are frequently lethal. We report the case of a young white man found dead in a hotel room after self-poisoning with cyanide ordered in the deep Web. This case shows a probable complex suicide kit use including cyanide, as a lethal tool, and dextromethorphan, as a sedative and anxiolytic substance. This case is an original example of the emerging deep Web shopping in illegal drug procurement. PMID- 27367576 TI - A Hanged From the Past: Medical Consideration on the Judas Iscariot Fresco Chapelle Notre-Dame-des-Fontaines, La Brigue (15th Century). AB - The medieval chapel of Notre Dame-des-Fontaines (Our Lady of the Fountains), in the French Maritime Alps, is entirely covered by the fresco cycle of the Passion (15th century) that depicts the last days of Jesus from the Last Supper to the Resurrection. Under a small window, there is the brutal representation of the suicide of Judas Iscariot, hanging from a tree, with the abdomen quartered from which his soul, represented by a small man, is kidnapped by a devil. The author, Giovanni Canavesio, represented the traitor's death with very detailed anatomical structures, differently thus from other paintings of the same subject; it is therefore possible to assume that the artist had become familiar with the human anatomy. In particular, the realism of the hanged man's posture, neck bent in an unnatural way, allows us to hypothesize that it probably comes from direct observation of the executions of capital punishment, not infrequently imposed by the public authorities in low medieval Italy. PMID- 27367577 TI - Diagnosis of a Cerebral Arteriovenous Malformation Using Isolated Brain Computed Tomography Angiography: Case Report. AB - This report presents a case of a 40-year-old woman who was found dead in her house. The examination of the body revealed no external injuries. The whole body was scanned by multi-detector-row computed tomography (CT) before autopsy, revealing massive hemorrhage in the right frontal extending into the ventricular system. At autopsy, the brain parenchyma was removed. Then CT angiography was carried on the isolated brain. Computed tomography angiography suggested a mass of irregular, tortuous vessels in areas of hemorrhage in the right frontal lobe of the brain. Finally, histological examination confirmed the result of CT angiography due to an arteriovenous malformation. Hence, postmortem CT angiography played an important role in diagnosis of the cerebral arteriovenous malformation that was responsible for a massive hemorrhage in the skull. PMID- 27367578 TI - Retrieval of past and future positive and negative autobiographical experiences. AB - We studied retrieval-induced forgetting for past or future autobiographical experiences. In the study phase, participants were given cues to remember past autobiographical experiences or to think about experiences that may occur in the future. In both conditions, half of the experiences were positive and half negative. In the retrieval-practice phase, for past and future experiences, participants retrieved either half of the positive or negative experiences using cued recall, or capitals of the world (control groups). Retrieval practice produced recall facilitation and enhanced memory for the practised positive and negative past and future experiences. While retrieval practice on positive experiences did not impair the recall of other positive experiences, we found inhibition for negative past and future experiences when participants practised negative experiences. Furthermore, retrieval practice on positive future experiences inhibited negative future experiences. These positivity biases for autobiographical memory may have practical implications for treatment of emotional disorders. PMID- 27367579 TI - Actinomadurol, an Antibacterial Norditerpenoid from a Rare Actinomycete, Actinomadura sp. KC 191. AB - A new secondary metabolite, actinomadurol (1), was isolated along with the known compound JBIR-65 (2) from a rare actinomycete, Actinomadura strain KC 191. The structure of 1 was established as a rare member of the bacterial C-19 norditerpenoid class by NMR data and ECD calculations. The absolute configuration of 2, which was previously reported without stereochemical analysis, was determined by using the modified Mosher's method and ECD calculations. Actinomadurol (1) exhibited potent antibacterial activity against pathogenic strains, such as Staphylococcus aureus, Kocuria rhizophila, and Proteus hauseri (MIC = 0.39-0.78 MUg/mL), whereas JBIR-65 (2) showed no antibacterial activity. PMID- 27367580 TI - Impact of 24/7 In-Hospital Intensivist Coverage on Outcomes in Pediatric Intensive Care. A Multicenter Study. AB - RATIONALE: The around-the-clock presence of an in-house attending critical care physician (24/7 coverage) is purported to be associated with improved outcomes among high-risk children with critical illness. OBJECTIVES: To evaluate the association of 24/7 in-house coverage with outcomes in children with critical illness. METHODS: Patients younger than 18 years of age in the Virtual Pediatric Systems Database (2009-2014) were included. The main analysis was performed using generalized linear mixed effects multivariable regression models. In addition, multiple sensitivity analyses were performed to test the robustness of our findings. MEASUREMENTS AND MAIN RESULTS: A total of 455,607 patients from 125 hospitals were included (24/7 group: 266,319 patients; no 24/7 group: 189,288 patients). After adjusting for patient and center characteristics, the 24/7 group was associated with lower mortality in the intensive care unit (ICU) (24/7 vs. no 24/7; odds ratio [OR], 0.52; 95% confidence interval [CI], 0.33-0.80; P = 0.002), a lower incidence of cardiac arrest (OR, 0.73; 95% CI, 0.54-0.99; P = 0.04), lower mortality after cardiac arrest (OR, 0.56; 95% CI, 0.340-0.93; P = 0.02), a shorter ICU stay (mean difference, -0.51 d; 95% CI, -0.93 to -0.09), and shorter duration of mechanical ventilation (mean difference, -0.68 d; 95% CI, -1.23 to 0.14). CONCLUSIONS: In this large observational study, we demonstrated that pediatric critical care provided in the ICUs staffed with a 24/7 intensivist presence is associated with improved overall patient survival and survival after cardiac arrest compared with patients treated in ICUs staffed with discretionary attending coverage. However, results from a few sensitivity analyses leave some ambiguity in these results. PMID- 27367581 TI - Correlation of Ocular Pulse Amplitude, Choroidal Thickness, and Internal Carotid Artery Doppler Ultrasound Findings in Normal Eyes. AB - INTRODUCTION: The choroid receives about 65-85% of ocular blood flow, which comes from the ophthalmic artery (OA), the first branch of the internal carotid artery (ICA). In the foveal avascular zone, there is no retinal vascular supply; therefore, choroidal blood supply plays a significant role in this subfoveal region. The ocular pulse amplitude (OPA) provides useful information about intraocular blood flow and is an indirect indicator of choroidal perfusion. In this study, we aimed to assess the correlation between the OPA, subfoveal choroidal thickness (CT), and ICA Doppler ultrasound findings in healthy eyes. METHODS: In total, 48 eyes of 48 healthy volunteers were included in this study. All eyes underwent detailed ophthalmic evaluation, including slit-lamp biomicroscopy, fundus examination, axial length, OPA measurements, and optical coherence tomography (OCT) with enhanced depth imaging mode. Carotid Doppler ultrasound examination was performed by the radiologist. The correlation between the OPA, subfoveal CT, and ICA Doppler findings [peak systolic velocity (PSV) and end-diastolic velocity (EDV)] were evaluated, considering gender and age. RESULTS: The mean OPA was 3.06 +/- 1.34 mmHg. The mean subfoveal CT was 305.85 +/ 33.98 um. The mean PSV and EDV of ICA were 73.25 +/- 23.63 cm/s and 26.93 +/- 13.42 cm/s, respectively. A moderate positive correlation was found between OPA and subfoveal CT (p = 0.001; rho = 0.481). This relationship was present in both men and women. While a positive correlation was found between the OPA and subfoveal CT in subjects under the age of 50 years, there was no correlation in those over the age of 50 years. CONCLUSIONS: A fair correlation was found between the OPA and subfoveal CT in healthy subjects under the age of 50. PMID- 27367582 TI - The thyroid and breast cancer. AB - PURPOSE OF REVIEW: The female predominance of diseases of the thyroid and breast makes difficult the separation of an expected association with a causal linkage. This review will examine recent reports on associations between thyroid disease and breast cancer, comparing them with previous studies, with a view to elucidating what pointers are available to suggest either a common pathogenesis or novel thyroid-related therapeutic approach, which might arise from this association. RECENT FINDINGS: Reports on thyroid-breast cancer associations are reviewed under the following headings: breast cancer prevalence in different thyroid disorders and their effect on risk and outcome; the possible role of thyroid autoimmunity, thyroid enlargement, effect of radioactive iodine treatment, role of stable iodine, possible joint antigens sodium iodide transporter and thyroid peroxidase and thyroid-breast cancer coincidence. SUMMARY: Current studies on thyroid and breast cancer associations confirm earlier findings of the lack of definitive evidence of a causal relationship. The predominant relationship continues to be hypothyroidism or autoimmune thyroid disease perhaps contributing to increased breast cancer risk or outcomes. However, despite many studies and the findings of meta-analyses, elucidating the mechanisms underlying the association remains elusive. At present, there is little justification for utilizing thyroid insights as a possible therapeutic intervention in breast cancer. PMID- 27367584 TI - Mitochondria-Targeting Chromogenic and Fluorescence Turn-On Probe for the Selective Detection of Cysteine by Caged Oxazolidinoindocyanine. AB - We report a chromogenic and fluorescence turn-on probe based on crotonoyl ester functionalized oxazolidinoindole for the selective detection of cysteine in neutral buffer. The probe rapidly formed indocyanophenolate through the Michael addition and a subsequent cyclization reaction of cysteine, inducing both a dramatic bathochromic shift (>130 nm) and a large fluorescence turn-on response (F/F0 12) in the UV-vis and fluorescence spectra and affording a micromolar limit of detection (LOD = 5.0 MUM) of cysteine in HEPES buffer. When cysteine was added, the probe exhibited a dual optical change with strong green fluorescence and dramatic red color by the oxazolidinoindole-to-hydroxyethylindolium transformation. Further cellular application of the probe was successfully performed for the mitochondrial imaging of HeLa cells. PMID- 27367583 TI - Neoadjuvant Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer: A Systematic Review and Meta-analysis. AB - Importance: Estrogen receptor-positive (ER+) tumors of the breast are generally highly responsive to endocrine treatment. Although endocrine therapy is the mainstay of adjuvant treatment for ER+ breast cancer, the role of endocrine therapy in the neoadjuvant setting is unclear. Objective: To evaluate the effect of neoadjuvant endocrine therapy (NET) on the response rate and the rate of breast conservation surgery (BCS) for ER+ breast cancer. Data Sources: Based on PRISMA guidelines, a librarian-led search of PubMed and Ovid MEDLINE was performed to identify eligible trials published from inception to May 15, 2015. The search was performed in May 2015. Study Selection: Inclusion criteria were prospective, randomized, neoadjuvant clinical trials that reported response rates with at least 1 arm incorporating NET (n = 20). Two authors independently analyzed the studies for inclusion. Data Extraction and Synthesis: Pooled odds ratios (ORs), 95% CIs, and P values were estimated for end points using the fixed and random-effects statistical model. Results: The analysis included 20 studies with 3490 unique patients. Compared with combination chemotherapy, NET as monotherapy with aromatase inhibitors had a similar clinical response rate (OR, 1.08; 95% CI, 0.50-2.35; P = .85; n = 378), radiological response rate (OR, 1.38; 95% CI, 0.92-2.07; P = .12; n = 378), and BCS rate (OR, 0.65; 95% CI, 0.41-1.03; P = .07; n = 334) but with lower toxicity. Aromatase inhibitors were associated with a significantly higher clinical response rate (OR, 1.69; 95% CI, 1.36-2.10; P < .001; n = 1352), radiological response rate (OR, 1.49; 95% CI, 1.18-1.89; P < .001; n = 1418), and BCS rate (OR, 1.62; 95% CI, 1.24-2.12; P < .001; n = 918) compared with tamoxifen. Dual combination therapy with growth factor pathway inhibitors was associated with a higher radiological response rate (OR, 1.59; 95% CI, 1.04-2.43; P = .03; n = 355), but not clinical response rate (OR, 0.76; 95% CI, 0.54-1.07; P = .11; n = 537), compared with endocrine monotherapy. The incidence of pathologic complete response was low (<10%). Conclusions and Relevance: Neoadjuvant endocrine therapy, even as monotherapy, is associated with similar response rates as neoadjuvant combination chemotherapy but with significantly lower toxicity, suggesting that NET needs to be reconsidered as a potential option in the appropriate setting. Additional research is needed to develop rational NET combinations and predictive biomarkers to personalize the optimal neoadjuvant strategy for ER+ breast cancer. PMID- 27367585 TI - Enrichment of Macular Pigment Enhances Contrast Sensitivity in Subjects Free of Retinal Disease: Central Retinal Enrichment Supplementation Trials - Report 1. AB - PURPOSE: The high-performance visual function associated with central vision is mediated by the macula (the central retina), which accumulates three diet-derived pigments (the carotenoids lutein [L], zeaxanthin [Z], and meso-zeaxanthin [MZ]). Our study sought to investigate the impact on visual function, including contrast sensitivity (CS), of supplementation with these naturally occurring carotenoids, in individuals with low retinal concentrations. METHODS: Subjects consumed daily a formulation containing 10 mg L, 2 mg Z, and 10 mg MZ (active group; n = 53) or placebo (n = 52) for a period of 12 months. Study visits were at baseline, 3, 6, and 12 months. Contrast sensitivity at 6 cycles per degree (cpd) was the primary outcome measure (POM). Secondary outcome measures included CS at other spatial frequencies, best-corrected visual acuity (BCVA), glare disability, photostress recovery, and light scatter. Macular pigment optical density (MPOD) was measured using dual-wavelength autofluorescence, and serum carotenoid concentrations were analyzed using high performance liquid chromatography (HPLC). RESULTS: Compared to placebo, statistically significant improvements from baseline CS were detected at 6 (P = 0.002) and 1.2 (P = 0.004) cpd in the active group. Additionally, improvements in CS were commensurate with the observed increases in retinal concentrations of these carotenoids (r = 0.342, P = 0.002 at 6 cpd). CONCLUSIONS: These results indicate that dietary fortification with the macular carotenoids can have meaningful effects on visual function. PMID- 27367586 TI - Stem Cell-Derived Photoreceptor Transplants Differentially Integrate Into Mouse Models of Cone-Rod Dystrophy. AB - PURPOSE: Preclinical studies on photoreceptor transplantation provided evidence for restoration of visual function with pluripotent stem cells considered as a potential source for sufficient amounts of donor material. Adequate preclinical models representing retinal disease conditions of potential future patients are needed for translation research. Here we compared transplant integration in mouse models with mild (prominin1-deficient; Prom1-/-) or severe (cone photoreceptor function loss 1/rhodopsin-deficient double-mutant; Cpfl1/Rho-/-) cone-rod degeneration. METHODS: For photoreceptor transplant production, we combined the mouse embryonic stem cell retinal organoid system with rhodopsin-driven GFP cell labeling by recombinant adeno-associated virus (AAV). Organoid-derived photoreceptors were enriched by CD73-based magnetic-activated cell sorting (MACS) and transplanted subretinally into wild-type, Prom1-/- and Cpfl1/Rho-/- hosts. The survival, maturation, and synapse formation of donor cells was analyzed by immunohistochemistry. RESULTS: Retinal organoids yielded high photoreceptor numbers that were further MACS-enriched to 85% purity. Grafted photoreceptors survived in the subretinal space of all mouse models. Some cells integrated into wild-type as well as Prom1-/- mouse retinas and acquired a mature morphology, expressing rod and synaptic markers in close proximity to second-order neurons. In contrast, in the novel Cpfl1/Rho-/- model with complete photoreceptor degeneration, transplants remained confined to the subretinal space, expressed rod-specific but only reduced synaptic markers, and did not acquire mature morphology. CONCLUSIONS: Comparison of photoreceptor grafts in preclinical models with incomplete or complete photoreceptor loss, showed differential transplant success with effective and impaired integration, respectively. Thus, Cpfl1/Rho-/- mice represent a potential benchmark model resembling patients with severe retinal degeneration to optimize photoreceptor replacement therapies. PMID- 27367587 TI - Using Stem Cells to Rebuild the Outer Neural Retina. PMID- 27367589 TI - A Comparison of Over-the-Counter Mechanical Nasal Dilators: A Systematic Review. AB - IMPORTANCE: The internal nasal valve is the narrowest part of the nasal airway and a common site of inspiratory collapse and obstruction of nasal airflow. Over the-counter mechanical nasal dilators are an alternative to surgical intervention that attempts to improve airflow through the internal nasal valve. OBJECTIVE: To determine the efficacy of over-the-counter mechanical nasal dilators and classify these products by mechanism. EVIDENCE REVIEW: A database of 33 available over-the counter mechanical nasal dilators was generated via a PubMed search as well as an internet search via Amazon.com and Google, conducted from April 1, 2013, through December 31, 2015. Products determined to be unavailable or discontinued were excluded from the database. Of the devices examined in published literature, efficacy was based on objective measures, such as measured airflow, the cross sectional area of the nasal valve, and changes in resistance. Measures of reported sleep quality or patient perception were excluded. FINDINGS: An analysis of each product's mechanism revealed 4 broad classes: external nasal dilator strips, nasal stents, nasal clips, and septal stimulators. A review demonstrated 5 studies supporting the use of external nasal dilator strips, 4 studies supporting the use of nasal clips, 1 study supporting the use of nasal stents, and no studies supporting the use of septal stimulators. CONCLUSIONS AND RELEVANCE: Our findings suggest that external nasal dilator strips and nasal clips effectively relieve obstruction of the internal nasal valve and may be an alternative to surgical intervention in some patients. PMID- 27367590 TI - Intra- and extracranial atherosclerotic disease: casting a new light on emerging trends. AB - Intra- and extracranial atherosclerotic stenosis has been shown to be associated with an increased risk of secondary stroke mortality. Advances in invasive and non-invasive imaging modalities have improved analysis of hemodynamic changes and allowed better delineation of the integrity of intracranial collateralization and plague morphology in patients with artery stenosis. This review focuses on new imaging modalities and clinical applications of currently available techniques, and provides significant insight into future directions in comprehensive analysis of intra- and extracranial atherosclerotic stenosis. PMID- 27367588 TI - Hypoxic-Preconditioned Bone Marrow Stem Cell Medium Significantly Improves Outcome After Retinal Ischemia in Rats. AB - PURPOSE: We have previously demonstrated the protective effect of bone marrow stem cell (BMSC)-conditioned medium in retinal ischemic injury. We hypothesized here that hypoxic preconditioning of stem cells significantly enhances the neuroprotective effect of the conditioned medium and thereby augments the protective effect in ischemic retina. METHODS: Rats were subjected to retinal ischemia by increasing intraocular pressure to 130 to 135 mm Hg for 55 minutes. Hypoxic-preconditioned, hypoxic unconditioned, or normoxic medium was injected into the vitreous 24 hours after ischemia ended. Recovery was assessed 7 days after injections by comparing electroretinography measurements, histologic examination, and apoptosis (TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay). To compare proteins secreted into the medium in the groups and the effect of hypoxic exposure, we used rat cytokine arrays. RESULTS: Eyes injected with hypoxic BMSC-conditioned medium 24 hours after ischemia demonstrated significantly enhanced return of retinal function, decreased retinal ganglion cell layer loss, and attenuated apoptosis compared to those administered normoxic or hypoxic unconditioned medium. Hypoxic preconditioned medium had 21 significantly increased protein levels compared to normoxic medium. CONCLUSIONS: The medium from hypoxic-preconditioned BMSCs robustly restored retinal function and prevented cell loss after ischemia when injected 24 hours after ischemia. The protective effect was even more pronounced than in our previous studies of normoxic conditioned medium. Prosurvival signals triggered by the secretome may play a role in this neuroprotective effect. PMID- 27367591 TI - The seductive allure is a reductive allure: People prefer scientific explanations that contain logically irrelevant reductive information. AB - Previous work has found that people feel significantly more satisfied with explanations of psychological phenomena when those explanations contain neuroscience information-even when this information is entirely irrelevant to the logic of the explanations. This seductive allure effect was first demonstrated by Weisberg, Keil, Goodstein, Rawson, and Gray (2008), and has since been replicated several times (Fernandez-Duque, Evans, Christian, & Hodges, 2015; Minahan & Siedlecki, 2016; Rhodes, Rodriguez, & Shah, 2014; Weisberg, Taylor, & Hopkins, 2015). However, these studies only examined psychological phenomena. The current study thus investigated the generality of this effect and found that it occurs across several scientific disciplines whenever the explanations include reductive information: reference to smaller components or more fundamental processes. These data suggest that people have a general preference for reductive information, even when it is irrelevant to the logic of an explanation. PMID- 27367592 TI - Qualitative differences in memory for vista and environmental spaces are caused by opaque borders, not movement or successive presentation. AB - Two classes of space define our everyday experience within our surrounding environment: vista spaces, such as rooms or streets which can be perceived from one vantage point, and environmental spaces, for example, buildings and towns which are grasped from multiple views acquired during locomotion. However, theories of spatial representations often treat both spaces as equal. The present experiments show that this assumption cannot be upheld. Participants learned exactly the same layout of objects either within a single room or spread across multiple corridors. By utilizing a pointing and a placement task we tested the acquired configurational memory. In Experiment 1 retrieving memory of the object layout acquired in environmental space was affected by the distance of the traveled path and the order in which the objects were learned. In contrast, memory retrieval of objects learned in vista space was not bound to distance and relied on different ordering schemes (e.g., along the layout structure). Furthermore, spatial memory of both spaces differed with respect to the employed reference frame orientation. Environmental space memory was organized along the learning experience rather than layout intrinsic structure. In Experiment 2 participants memorized the object layout presented within the vista space room of Experiment 1 while the learning procedure emulated environmental space learning (movement, successive object presentation). Neither factor rendered similar results as found in environmental space learning. This shows that memory differences between vista and environmental space originated mainly from the spatial compartmentalization which was unique to environmental space learning. Our results suggest that transferring conclusions from findings obtained in vista space to environmental spaces and vice versa should be made with caution. PMID- 27367593 TI - Chunk formation in immediate memory and how it relates to data compression. AB - This paper attempts to evaluate the capacity of immediate memory to cope with new situations in relation to the compressibility of information likely to allow the formation of chunks. We constructed a task in which untrained participants had to immediately recall sequences of stimuli with possible associations between them. Compressibility of information was used to measure the chunkability of each sequence on a single trial. Compressibility refers to the recoding of information in a more compact representation. Although compressibility has almost exclusively been used to study long-term memory, our theory suggests that a compression process relying on redundancies within the structure of the list materials can occur very rapidly in immediate memory. The results indicated a span of about three items when the list had no structure, but increased linearly as structure was added. The amount of information retained in immediate memory was maximal for the most compressible sequences, particularly when information was ordered in a way that facilitated the compression process. We discuss the role of immediate memory in the rapid formation of chunks made up of new associations that did not already exist in long-term memory, and we conclude that immediate memory is the starting place for the reorganization of information. PMID- 27367594 TI - Pattern and Predictors of Medication Dosing Errors in Chronic Kidney Disease Patients in Pakistan: A Single Center Retrospective Analysis. AB - BACKGROUND: Chronic kidney disease (CKD) alters the pharmacokinetic and pharmacodynamic response of various drugs and increases the risk of toxicity. The data regarding the pattern and predictors of medication dosing errors is scare from the developing countries. Therefore, the present study was conducted to assess the pattern and predictors of medication dosing errors in CKD patients in a tertiary care setting in Pakistan. METHODS: A retrospective study design was employed and medical charts of all those CKD patients who had an eGFR <=60ml/min/1.73m2, hospitalization >=24 hours, and admitted in the nephrology unit during January 2013 to December 2014 were assessed. Descriptive statistics and the logistic regression analysis were done using IBM SPSS version 20. RESULTS: In total, 205 medical charts were assessed. The mean age of patients was 38.64 (+/-16.82) years. Overall, 1534 drugs were prescribed to CKD patients, of which, nearly 34.0% drugs required dose adjustment. Among those drugs, only 41.8% were properly adjusted, and the remaining 58.2% were unadjusted. The logistic regression analysis revealed that the medication dosing errors were significantly associated with the CKD stages, i.e. stage 4 (OR 0.054; 95% CI [0.017-0.177]; p <0.001) and stage 5 (OR 0.098; 95% CI [0.040-0.241]; p <0.001), the number of prescribed medicines >= 5 (OR 0.306; 95% CI [0.133-0.704]; p 0.005), and the presence of a comorbidity (OR 0.455; 95% CI [0.226-0.916]; p 0.027) such as the hypertension (OR 0.453; 95% CI [0.231-0.887]; p 0.021). CONCLUSIONS: It is concluded that more than half drugs prescribed to CKD patients requiring dose adjustment were unadjusted. The predictors of medication dosing errors were the severe-to-end stages of chronic kidney disease, the presence of a comorbidity such as hypertension, and a higher number of prescribed medicines. Therefore, attention should be paid to these risk factors. PMID- 27367595 TI - Benign prostatic hyperplasia: A clinical review. AB - Benign prostatic hyperplasia (BPH) is an increasingly common diagnosis seen in men over age 50 years. Primary care providers must be aware of patient presentation, diagnostic tests, appropriate lifestyle modifications, treatment options, and potential complications in order to properly manage and educate patients with BPH. If left untreated, BPH can significantly decrease a man's quality of life; however, many pharmacologic and surgical treatments are available to control the symptoms. PMID- 27367596 TI - Royce W. Murray. PMID- 27367597 TI - Presence of HHV-6A in Endometrial Epithelial Cells from Women with Primary Unexplained Infertility. AB - To elucidate the roles of human herpesvirus (HHV)-6 primary unexplained infertile women, a prospective randomized study was conducted on a cohort of primary unexplained infertile women and a cohort of control women, with at least one successful pregnancy. HHV-6 DNA was analyzed and the percentage and immune phenotype of resident endometrial Natural Killer (NK) cells, as the first line of defense towards viral infections, was evaluated in endometrial biopsies. Cytokine levels in uterine flushing samples were analyzed. HHV-6A DNA was found in 43% of endometrial biopsies from primary unexplained infertile women, but not in control women. On the contrary, HHV-6B DNA was absent in endometrial biopsies, but present in PBMCs of both cohorts. Endometrial NK cells presented a different distribution in infertile women with HHV6-A infection compared with infertile women without HHV6-A infection. Notably, we observed a lower percentage of endometrial specific CD56brightCD16- NK cells. We observed an enhanced HHV-6A specific endometrial NK cell response in HHV-6A positive infertile women, with a marked increase in the number of endometrial NK cells activating towards HHV-6A infected cells. The analysis of uterine flushing samples showed an increase in IL 10 levels and a decrease of IFN-gamma concentrations in infertile women with HHV6 A infection. Our study indicates, for the first time, that HHV-6A infection might be an important factor in female unexplained infertility development, with a possible role in modifying endometrial NK cells immune profile and ability to sustain a successful pregnancy. PMID- 27367598 TI - Cationic Two-Photon Lanthanide Bioprobes Able to Accumulate in Live Cells. AB - An original cationic water-soluble cyclen-based Eu(III) complex [EuL(1)](+) featuring a chromophore-functionalized antenna to increase the two-photon (2P) absorption properties was synthesized. The photophysical properties were thoroughly studied in various solvents and rationalized with the help of theoretical calculations. The complex exhibits an optimized 2P absorption cross section. Finally, 2P microscopy imaging experiments on living T24 human cancer cells highlighted the spontaneous internalization and the biological stability of this 2P bioprobe in vitro. Macrocyclic-based antennas open new perspectives for future optimization of the photophysical properties and allows envisaging the design of Eu, Tb, Yb, and Sm bioprobes. This result also opens the way for the design of functional two-photon Ln complexes able to monitor intracellular physicochemical parameters. PMID- 27367599 TI - Noninvasively detecting Isocitrate dehydrogenase 1 gene status in astrocytoma by dynamic susceptibility contrast MRI. AB - PURPOSE: To investigate the value of dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) in the noninvasive evaluation of isocitrate dehydrogenase (IDH) 1 gene status in astrocytoma. MATERIALS AND METHODS: The preoperative DSC MRI data of 91 lesions with pathologically confirmed astrocytoma were retrospectively analyzed. MR examination was performed on a 3T MRI scanner. The normalized maximum ratios of relative cerebral blood volume (rCBV ratio) of tumor parenchyma were measured. The enrolled astrocytoma patients were divided into six groups according to the World Health Organization (WHO) classification method and IDH1 gene status. The differences in the rCBV ratio of tumor parenchyma between the IDH1 gene mutant and wildtype groups of WHO grade II, III, and IV were compared and plotted receiver operating characteristic (ROC) curves were drawn. RESULTS: The IDH1 gene mutant and wildtype groups of WHO grade II, III, and IV astrocytoma showed differences in the rCBV ratio (P = 0.005, 0.045, and 0.005, respectively). In WHO grade II, III, and IV astrocytoma, the area under the ROC curve was respectively 0.83, 0.86, and 0.94. The cutoff value of the rCBV ratio was respectively 2.20, 3.14, and 5.63. CONCLUSION: The rCBV ratio value provided by DSC MRI provides a new potential imaging method for the noninvasive evaluation of the IDH1 status in astrocytoma. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:492-499. PMID- 27367600 TI - An Investigation Into the Relationship Between Long-term Posttraumatic Stress Disorder Symptoms and Coping in Australian Volunteer Firefighters. AB - This study examined the relationship between coping style and long-term posttraumatic stress symptoms in an Australian sample of volunteer firefighters 84 months following a bushfire disaster. A total of 277 firefighters completed 4 questionnaires to assess patterns of psychiatric morbidity. A 2-way repeated measures analysis of variance was conducted to investigate the effect of time and disorder on coping. Firefighters evidencing distress were more likely to use both problem- and emotion-focused methods of coping. Based on previous research, it was hypothesized that problem-focused coping strategies would be used after 84 months. The use of both problem- and emotion-focused coping may be due to the length of time following this disaster or unique characteristics of firefighters. These data suggest that present coping theories are not sufficient to account for the onset and pattern of psychiatric morbidity within a firefighter sample. The authors declare no conflicts of interest including financial, consultant, institutional, and other relationships that might lead to bias. PMID- 27367601 TI - Elite synchronized swimmers display decreased energy availability during intensified training. AB - Elite synchronized swimmers follow high-volume training regimen that result in elevated rates of exercise energy expenditure (ExEE). While adequate energy intake (EI) is important to optimize recovery, a number of sport-specific constraints may lead to chronically low energy availability (EA = EI-ExEE). This study aimed to quantify changes in EA, endocrine markers of energy conservation, and perceived fatigue in synchronized swimmers, during a week of baseline training followed by 4 weeks of intensified training (IT). EI, ExEE, and body composition were measured in nine swimmers at Baseline, midpoint (ITWK2 ), and end of IT (ITWK4 ). Waking saliva samples were obtained to measure [leptin]s , [ghrelin]s , and [cortisol]s . Fatigue ratings were provided daily. ExEE increased by 27% during IT. Swimmers increased EI from Baseline to ITWK2 , but decreased it significantly from ITWK2 to ITWK4 . EA, fat mass, and [leptin]s decreased from Baseline to ITWK4 , while [ghrelin]s increased significantly. Fatigue at ITWK4 was inversely correlated with Baseline EI and EA. The significant decrease in EA was accompanied by endocrine signs of energy conservation in elite swimmers. As perceived fatigue was associated with low EA, particular attention should be paid to these athletes' energy intake during phases of heavy training. PMID- 27367602 TI - Association between Serum Bilirubin and Acute Intraoperative Hyperglycemia Induced by Prolonged Intermittent Hepatic Inflow Occlusion in Living Liver Donors. AB - BACKGROUND: Intermittent hepatic inflow occlusion (IHIO) is associated with acute hyperglycemia during living donor hepatectomy when the ischemia is prolonged. Bilirubin is a potent antioxidant to play an important role for maintaining insulin sensitivity and preventing hyperglycemia. Thus, we aimed to test whether serum bilirubin level is associated with prolonged IHIO-induced intraoperative hyperglycemia. METHODS: Seventy-five living liver donors who underwent a prolonged IHIO with a >30 minute cumulative ischemia were included. The association between preoperative serum bilirubin concentrations and the risk of intraoperative hyperglycemia (blood glucose concentration >180 mg/dl) was analyzed using binary logistic regression with adjusting for potential confounders including age and steatosis. RESULTS: The number of donors who underwent 3, 4, 5, and 6 rounds of IHIO was 41, 22, 7, and 5, respectively. Twenty-nine (35%) donors developed intraoperative hyperglycemia. Total bilirubin concentration was inversely associated with hyperglycemia risk (odds ratio [OR] 0.033, 95% confidence interval [CI] 0.004-0.313, P = 0.003). There was an interaction between age and total bilirubin concentration: the effect of lower serum total bilirubin (<=0.7 mg/dl) on the development of hyperglycemia was greater in older donors (>40 years) than in younger donors (P = 0.0.028 versus P = 0.212). Both conjugated bilirubin (OR 0.001 95% CI 0.001-0.684) and unconjugated bilirubin (OR 0.011 95% CI 0.001-0.246) showed an independent association with hyperglycemia risk. CONCLUSIONS: Lower preoperative serum bilirubin was associated with greater risk of prolonged IHIO-induced hyperglycemia during living donor hepatectomy particularly in older donors. Thus, more meticulous glycemic management is recommended when prolonged IHIO is necessary for surgical purposes in old living donors with lower serum bilirubin levels. PMID- 27367603 TI - Doctors' Perceptions and Practices of Breaking Bad News: A Qualitative Study From Greece. AB - There is limited information about doctors' communication behaviors and their salient beliefs with regard to bad news disclosure in Greece. In this qualitative study we investigated the self-reported practices of doctors on breaking bad news, their perceptions about the factors affecting the delivery of such news, and their beliefs about the most appropriate disclosure manner. A focus group discussion and individual interviews were conducted. Twenty-five resident and specialist doctors from primary health care and hospital settings participated. We analyzed the collected data with content analysis techniques. Participants were found to acknowledge the importance of appropriate and effective delivery of bad news; however, none of them reported the implementation of empirically informed communication practices. They described communication patterns mainly formed by their work experience and often guided by the patient's family requests. Doctor, patient, and family characteristics and organizational features and resources were reported to affect the delivery of bad news. Participants perceived the most appropriate disclosure manner as an individualized approach to each patient's unique needs. They suggested an interdisciplinary, collaborative management of the delivery process and the establishment of formal supportive services. These findings may provide useful information for the development of tailored, empirically informed curriculum interventions and educational programs in order to address several barriers to communication. Sociocultural characteristics that influence the disclosure practice, as well as physicians' perceptions that are consistent with the optimal information delivery, should be taken into account. System-level strategies that focus on the development of patient-centered communication also need to be prioritized. PMID- 27367604 TI - Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice. AB - One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic system from space radiation. PMID- 27367605 TI - Bilateral Sequential Profound Visual Loss in Tuberous Sclerosis. AB - Tuberous sclerosis is a rare, autosomal dominant condition characterized by multiple systemic benign tumor growths. Ocular manifestations include the development of retinal and optic nerve head astrocytic hamartomas. Retinal astrocytic hamartomas are benign, uncommon lesions which rarely progress or cause deterioration in visual function. We present a case of profound visual loss in a 17-year-old male with tuberous sclerosis. He had multiple intracranial lesions which had been debulked, secondary hydrocephalus which was shunted, swollen optic nerves, and asymmetric astrocytic hamartomas of the optic nerve head and retina. He was subsequently registered with severe visual impairment. This case demonstrates complex interactions and mechanisms precipitating unexpected catastrophic bilateral loss of vision in a teenage boy in a condition which rarely impacts visual outcome. PMID- 27367607 TI - Pesticides in Brazilian freshwaters: a critical review. AB - The widespread use of pesticides in agriculture can lead to water contamination and cause adverse effects on non-target organisms. Brazil has been the world's top pesticide market consumer since 2008, with 381 approved pesticides for crop use. This study provides a comprehensive literature review on the occurrence of pesticide residues in Brazilian freshwaters. We searched for information in official agency records and peer-reviewed scientific literature. Risk quotients were calculated to assess the potential risk posed to aquatic life by the individual pesticides based on their levels of water contamination. Studies about the occurrence of pesticides in freshwaters in Brazil are scarce and concentrated in few sampling sites in 5 of the 27 states. Herbicides (21) accounted for the majority of the substances investigated, followed by fungicides (11), insecticides (10) and plant growth regulators (1). Insecticides are the class of major concern. Brazil would benefit from the implementation of a nationwide pesticide freshwater monitoring program to support preventive, remediation and enforcement actions. PMID- 27367606 TI - Prevalence and Predictors of Persistent Speech Sound Disorder at Eight Years Old: Findings From a Population Cohort Study. AB - PURPOSE: The purpose of this study was to determine prevalence and predictors of persistent speech sound disorder (SSD) in children aged 8 years after disregarding children presenting solely with common clinical distortions (i.e., residual errors). METHOD: Data from the Avon Longitudinal Study of Parents and Children (Boyd et al., 2012) were used. Children were classified as having persistent SSD on the basis of percentage of consonants correct measures from connected speech samples. Multivariable logistic regression analyses were performed to identify predictors. RESULTS: The estimated prevalence of persistent SSD was 3.6%. Children with persistent SSD were more likely to be boys and from families who were not homeowners. Early childhood predictors identified as important were weak sucking at 4 weeks, not often combining words at 24 months, limited use of word morphology at 38 months, and being unintelligible to strangers at age 38 months. School-age predictors identified as important were maternal report of difficulty pronouncing certain sounds and hearing impairment at age 7 years, tympanostomy tube insertion at any age up to 8 years, and a history of suspected coordination problems. The contribution of these findings to our understanding of risk factors for persistent SSD and the nature of the condition is considered. CONCLUSION: Variables identified as predictive of persistent SSD suggest that factors across motor, cognitive, and linguistic processes may place a child at risk. PMID- 27367608 TI - Juvenile Xanthogranuloma: Presenting as an Isolated Renal Involvement. AB - Juvenile xanthogranuloma (JXG) is a histiocytic disorder of childhood that mostly affects the skin although extracutaneous and visceral manifestations are well documented in English literature. The renal involvement is less commonly documented as a manifestation of xanthogranuloma and the reported cases occur in conjunction with cutaneous xanthogranuloma, especially in association with multiple skin lesions. We present a case of isolated renal JXG presenting as a renal mass with perinephric soft tissue and muscle involvement but without any cutaneous manifestation. This is the first case report of renal JXG without cutaneous involvement, to the best of our knowledge. PMID- 27367610 TI - Secret Forwarding of Events over Distributed Publish/Subscribe Overlay Network. AB - Publish/subscribe is a communication paradigm where loosely-coupled clients communicate in an asynchronous fashion. Publish/subscribe supports the flexible development of large-scale, event-driven and ubiquitous systems. Publish/subscribe is prevalent in a number of application domains such as social networking, distributed business processes and real-time mission-critical systems. Many publish/subscribe applications are sensitive to message loss and violation of privacy. To overcome such issues, we propose a novel method of using secret sharing and replication techniques. This is to reliably and confidentially deliver decryption keys along with encrypted publications even under the presence of several Byzantine brokers across publish/subscribe overlay networks. We also propose a framework for dynamically and strategically allocating broker replicas based on flexibly definable criteria for reliability and performance. Moreover, a thorough evaluation is done through a case study on social networks using the real trace of interactions among Facebook users. PMID- 27367611 TI - [Correction: Future Trends in Medical Rehabilitation in the Context of Multimorbidity - Part I: Definition of Terms, Issues and Challenges]. AB - W. SEGER, W. CIBIS, A. DEVENTER, S. GROTKAMP, N. LuBKE, P.-W. SCHoNLE, M. SCHUBERT. DIE ZUKUNFT DER MEDIZINISCH-REHABILITATIVEN VERSORGUNG IM KONTEXT DER MULTIMORBIDITaT - TEIL I: BEGRIFFSBESTIMMUNG, VERSORGUNGSFRAGEN UND HERAUSFORDERUNGEN KuNSTLERISCHE THERAPEUTEN IM GESUNDHEITSWESEN. GESUNDHEITSWESEN 2016;: Bei diesem Beitrag fehlte ein Autor und die zugehorige Institutsangabe. Nachfolgend die erganzten Autoren und Institute: AUTOREN:: W. Seger1, W. Cibis2, A. Deventer3, S. Grotkamp4, N. Lubke5, P.-W. Schonle6, M. Schmidt-Ohlemann7, M. Schubert2 INSTITUTE:: 1 MDK Niedersachsen, Hannover 2 Bundesarbeitsgemeinschaft fur Rehabilitation (BAR), Frankfurt 3 Praxis fur Physikalische und Rehabilitative Medizin, Hamburg 4 MDK Niedersachsen, SEG 1, Hannover 5 Kompetenz-Centrum Geriatrie (KCG), Hamburg 6 Maternus Kliniken, Bad Oeynhausen 7 Diakonie Bad Kreuznach, Rehabilitationsklinik, Bad Kreuznach. PMID- 27367609 TI - A High Temperature-Dependent Mitochondrial Lipase EXTRA GLUME1 Promotes Floral Phenotypic Robustness against Temperature Fluctuation in Rice (Oryza sativa L.). AB - The sessile plants have evolved diverse intrinsic mechanisms to control their proper development under variable environments. In contrast to plastic vegetative development, reproductive traits like floral identity often show phenotypic robustness against environmental variations. However, it remains obscure about the molecular basis of this phenotypic robustness. In this study, we found that eg1 (extra glume1) mutants of rice (Oryza savita L.) showed floral phenotypic variations in different growth locations resulting in a breakdown of floral identity robustness. Physiological and biochemical analyses showed that EG1 encodes a predominantly mitochondria-localized functional lipase and functions in a high temperature-dependent manner. Furthermore, we found that numerous environmentally responsive genes including many floral identity genes are transcriptionally repressed in eg1 mutants and OsMADS1, OsMADS6 and OsG1 genetically act downstream of EG1 to maintain floral robustness. Collectively, our results demonstrate that EG1 promotes floral robustness against temperature fluctuation by safeguarding the expression of floral identify genes through a high temperature-dependent mitochondrial lipid pathway and uncovers a novel mechanistic insight into floral developmental control. PMID- 27367612 TI - Understanding the Link Between Cannabinoids and Psychosis. AB - The changing legal landscape surrounding cannabis is likely a contributing factor to the increasing rates of cannabis use worldwide. Accordingly, consequences of cannabis use translate into sizeable public health implications. While the medicinal purposes of cannabis are often sensationalized, information regarding its harmful effects is largely confined to the scientific community. Therefore, educational campaigns informing the public about the links between cannabinoids and psychosis are urgently needed. PMID- 27367613 TI - Trends in Breastfeeding Initiation and Duration by Birth Weight Among US Children, 1999-2012. PMID- 27367614 TI - Impact of newer self-monitoring technology and brief phone-based intervention on weight loss: A randomized pilot study. AB - OBJECTIVE: Despite the proliferation of newer self-monitoring technology (e.g., activity monitors and smartphone apps), their impact on weight loss outside of structured in-person behavioral intervention is unknown. METHODS: A randomized, controlled pilot study was conducted to examine efficacy of self-monitoring technology, with and without phone-based intervention, on 6-month weight loss in adults with overweight and obesity. Eighty participants were randomized to receive standard self-monitoring tools (ST, n = 26), technology-based self monitoring tools (TECH, n = 27), or technology-based tools combined with phone based intervention (TECH + PHONE, n = 27). All participants attended one introductory weight loss session and completed assessments at baseline, 3 months, and 6 months. RESULTS: Weight loss from baseline to 6 months differed significantly between groups P = 0.042; there was a trend for TECH + PHONE (-6.4 +/- 1.2 kg) to lose more weight than ST (-1.3 +/- 1.2 kg); weight loss in TECH ( 4.1 +/- 1.4 kg) was between ST and TECH + PHONE. Fewer ST (15%) achieved >=5% weight losses compared with TECH and TECH + PHONE (44%), P = 0.039. Adherence to self-monitoring caloric intake was higher in TECH + PHONE than TECH or ST, Ps < 0.05. CONCLUSIONS: These results suggest use of newer self-monitoring technology plus brief phone-based intervention improves adherence and weight loss compared with traditional self-monitoring tools. Further research should determine cost effectiveness of adding phone-based intervention when providing self-monitoring technology. PMID- 27367615 TI - Towards antiviral therapies for treating dengue virus infections. AB - Dengue virus is an emerging human pathogen that poses a huge public health burden by infecting annually about 390 million individuals of which a quarter report with clinical manifestations. Although progress has been made in understanding dengue pathogenesis, a licensed vaccine or antiviral therapy against this virus is still lacking. Treatment of patients is confined to symptomatic alleviation and supportive care. The development of dengue therapeutics thus remains of utmost importance. This review focuses on the few molecules that were evaluated in dengue virus-infected patients: balapiravir, chloroquine, lovastatin, prednisolone and celgosivir. The lessons learned from these clinical trials can be very helpful for the design of future trials for the next generation of dengue virus inhibitors. PMID- 27367616 TI - Predicting hydration free energies of amphetamine-type stimulants with a customized molecular model. AB - Amphetamine-type stimulants (ATS) are a group of incitation and psychedelic drugs affecting the central nervous system. Physicochemical data for these compounds are essential for understanding the stimulating mechanism, for assessing their environmental impacts, and for developing new drug detection methods. However, experimental data are scarce due to tight regulation of such illicit drugs, yet conventional methods to estimate their properties are often unreliable. Here we introduce a tailor-made multiscale procedure for predicting the hydration free energies and the solvation structures of ATS molecules by a combination of first principles calculations and the classical density functional theory. We demonstrate that the multiscale procedure performs well for a training set with similar molecular characteristics and yields good agreement with a testing set not used in the training. The theoretical predictions serve as a benchmark for the missing experimental data and, importantly, provide microscopic insights into manipulating the hydrophobicity of ATS compounds by chemical modifications. PMID- 27367617 TI - Patient-Centered Outcomes Research-Opportunities for Novel, Innovative, and Transformative Partnerships With Patients and Their Families. PMID- 27367618 TI - Studies of the binding mode of TXNHCH2COOH with calf thymus DNA by spectroscopic methods. AB - In this study, a thioxanthone derivative named 2-(9-oxo-9H-thioxanthen-2ylamino) acetic acid (TX-NHCH2COOH) was used to investigate small molecule and DNA binding interactions. Absorption and fluorescence emission spectroscopy were used and melting studies were used to explain the binding mode of TXNHCH2COOH-DNA. Intrinsic binding constant Kb TXNHCH2COOH was found 6*10(5)M(-1)from UV-Vis absorption spectroscopy. Fluorescence emmision intensity increased by adding ct DNA to the TXNHCH2COOH and KI quenching experiments resulted with low Ksv value. Additionally, 3.7 degrees C increase for Tm was observed. The observed quenching of EB and ct-DNA complex and increase viscosity values of ct-DNA by addition of TXNHCH2COOH was determined. All those results indicate that TXNHCH2COOH can intercalate into DNA base pairs. Fluorescence microscopy helped to display imaging of the TXNHCH2COOH-DNA solution. PMID- 27367619 TI - Availability and Dissemination of Results From US Food and Drug Administration Mandated Postapproval Studies for Medical Devices. PMID- 27367620 TI - Current and investigational drugs for the treatment of diabetic retinopathy. AB - INTRODUCTION: Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are the two complications of diabetes that cause visual loss and blindness. Laser photo-coagulation in the past was used to prevent progression of disease to these advanced stages. Advances in pathophysiologic understanding of DME and PDR have ushered the development of effective targeted therapy that given intravitreally improves vision and prevents blindness. While effective, these therapies require frequent administration and are not universally effective. AREAS COVERED: This purpose of this paper is to review the current pathophysiologic understanding and treatments for DME and PDR as well as the novel treatments currently being developed. The treatments will be juxtaposed to the factor in the disease cascade being targeted. The potential role of these novel treatment in the clinical armamentarium are postulated. EXPERT OPINION: Mono-therapy, single category targeting is the current strategy being utilized clinically. However, diabetic retinopathy needs combination therapy. Therapies that will prove successful will address multiple factors involved in the pathogenesis of diabetic retinopathy. PMID- 27367624 TI - Renewal. PMID- 27367621 TI - Enhancing the Apoptotic Effect of a Low Dose of Paclitaxel on Tumor Cells in Mice by Arabinoxylan Rice Bran (MGN-3/Biobran). AB - In this study, we examine the ability of arabinoxylan rice bran (MGN-3/Biobran) to enhance the apoptotic effect of paclitaxel (Taxol) at low concentration [2 mg/kg body weight (BW)] in animals bearing Ehrlich ascites carcinoma (EAC) cells and elucidate its mechanisms of action. On Day 8 following tumor cells inoculation, mice bearing tumors were administered MGN-3 alone (40 mg/kg BW), paclitaxel alone, or MGN-3 plus paclitaxel. On Day 30 post-tumor inoculation, we observed significant suppression of tumor volume (TV) with paclitaxel alone (59%), MGN-3 alone (77%), and MGN-3 plus paclitaxel (88%). Inhibition of tumor growth post-treatment with both agents, as compared with either treatment alone, was associated with a decrease in cell proliferation, a marked increase in the sub-G0/G1 population, an increase in DNA damage and apoptosis of tumor cells, and a significant maximization of the apoptosis index (AI)/proliferation index (PrI) ratio. Histopathological and electron microscopy examination of the combined treatment group showed an increase in the degenerative regions of the solid tumor tissue and abundant apoptotic cells. These data suggest that MGN-3 supplementation enhances tumor cell demise in the presence of a low dose of chemotherapeutic agent via apoptotic mechanism. PMID- 27367625 TI - Corralling the Class II composite resin restoration. PMID- 27367626 TI - Pushing it to the limits. PMID- 27367627 TI - Dental surgical management of the patient with hemophilia. AB - The dental surgical management of a patient with a bleeding disorder can present a challenge to the dental provider. This article reviews the clinical presentation of hemophilia and describes the management of 2 patients with hemophilia who presented for dental extractions. Each patient's hematologist was consulted to determine clotting factor replacement therapy, antifibrinolytic therapy, and local measures to obtain hemostasis perioperatively. Careful coordination with the patient's hematologist in such cases is essential to ensure safe treatment. PMID- 27367628 TI - What every dentist should know about coffee. AB - Coffee is one of the most widely consumed beverages throughout the world. Its stimulating nature is responsible for much of its popularity, which paradoxically has resulted in its reputation for negative effects on consumer health. This review will address recent research on the systemic and dental health effects of coffee. Many of its supposed harmful effects have been disproved, while many protective and beneficial roles for coffee are emerging. PMID- 27367629 TI - Effect of occlusal calculus utilized as a potential "biological sealant" in special needs patients with gastric feeding tubes: a qualitative in vitro contrast to pit and fissure sealant restorations. AB - The aim of this case report and in vitro investigation was to evaluate the marginal microleakage of intact occlusal calculus of primary molars extracted from a special needs patient who received nutrition via a gastric feeding tube. An adolescent with a history of developmental disturbance presented for routine dental care in a hospital facility. Prophylaxis was performed, and 2 mandibular permanent molars were restored. Five primary molars were extracted due to mobility and delayed retention. Heavy deposits of intact calculus were present on the occlusal surfaces of the primary teeth. The extracted teeth were immersed in methylene blue dye solution, invested in acrylic resin, sectioned into blocks, and photographed at 20* and 40* magnification. Previously photographed calculus free molars with pit and fissure sealants were reviewed and served as contrasting "restorations." The occlusal calculus on the primary teeth extracted from the patient absorbed the dye, while the comparison teeth containing pit and fissure sealants exhibited varying degrees of marginal dye penetration (microleakage). No marginal microleakage was noted in the calculus specimens, indicating that this substrate may serve as a "natural" occlusal surface sealant and that its removal from occlusal surfaces during routine oral prophylaxis may be unnecessary. PMID- 27367630 TI - Maintenance of pulpal vitality in a tooth with deep caries: a case report. AB - Deep caries can induce severe inflammatory reactions. However, inflamed pulp can heal if the demineralization process is interrupted and inactivated sufficiently early. The aim of this case report is to describe the use of stepwise excavation to treat a mature permanent tooth that exhibited deep caries and apical periodontitis. A 12-year-old girl was experiencing lingering pain lasting for a few minutes in the mandibular left second molar when drinking cold water. Clinical and radiographic examinations suggested that a conservative therapeutic approach could be successful. The tooth was anesthetized and isolated, and the unsupported enamel was removed. The remaining affected dentin was left on the pulpal floor, which was protected by a thin layer of calcium hydroxide cement. The tooth was sealed with temporary cement. Three months later, pulpal sensitivity was reduced. The pulp was found to be healthy at a 9-month follow-up examination. The cavity was definitively restored with glass ionomer cement and composite resin applied with the sandwich technique. At the 4-year follow-up, the tooth remained functional, presenting standard color and satisfactory restoration. The periodontal tissues were healthy, and radiographic images indicated that the width of the periodontal ligament space was normal. This case demonstrates that clinical diagnosis should prevail over radiographic findings, even in cases where a radiographic widening of the periodontal ligament space suggests irreversible pulpal damage. PMID- 27367631 TI - Biocompatibility of a restorative resin-modified glass ionomer cement applied in very deep cavities prepared in human teeth. AB - This study evaluated whether a restorative resin-modified glass ionomer cement, Vitremer (VM), would be biocompatible with pulp tissue when used as a liner in very deep cavities prepared in young human permanent teeth. Two dental cements in current use as liner materials, Vitrebond (VB) and Dycal (DY), were compared to VM. Class V cavities were prepared in 36 sound premolars that were scheduled for extraction, and the cavity floor was lined with the restorative cement (VM) or a liner/base control cement (VB or DY). For VM specimens, the cavity floor was pretreated with a primer (polyacrylic acid plus 2-hydroxyethyl methacrylate). Teeth were extracted after 7 or 30 days and processed for microscopic evaluation. In the VM group, inward diffusion of dental material components through dentinal tubules, associated with disruption of the odontoblastic layer, moderate to intense inflammatory response, and resorption of inner dentin, was observed in 2 teeth at 7 days. These histologic features were observed in 1 tooth at 30 days. In the VB group, mild inflammatory reactions and tissue disorganization observed at 7 days were resolved at 30 days. No pulpal damage occurred in the DY specimens. Of the materials tested, only Vitremer was not considered biocompatible, because it caused persistent pulpal damage when applied in very deep cavities (remaining dentin thickness less than 0.3 mm). PMID- 27367632 TI - Conservative management of external root resorption after tooth reimplantation: a 3-year follow-up. AB - The aim of this case report is to describe the treatment of a 9-year-old patient who suffered external root resorption of the permanent maxillary left lateral incisor following reimplantation of the avulsed left central and lateral incisors. Sixteen days after reimplantation and splinting of the incisors in a hospital emergency department, the patient was brought to the pediatric department of a dental school for further treatment. Root canal access was created in the maxillary left lateral and central incisors, and calcium hydroxide paste was used as intracanal dressing. At the 5-month follow-up, a radiograph revealed extensive external root resorption, a communicating root canal, and a periodontal lesion affecting the left lateral incisor. Management of the root resorption included obturation of the apical third of the canal with gutta percha and the middle third with mineral trioxide aggregate (MTA). At the 3-year recall examination, the patient was asymptomatic, and no mobility or soft tissue alterations were observed clinically. There was no radiographic sign that resorption had progressed. Despite the success of treatment, observation is still required. The use of MTA may be considered an alternative treatment for external root resorption after tooth reimplantation. The technique may allow tooth preservation in children until skeletal growth and development are completed and implant treatment may be considered. PMID- 27367633 TI - Shear bond strength comparison of implant-retained overdenture attachment pickup materials. AB - This study evaluated the shear bond strength (SBS) of 4 different retentive materials for the chairside pickup of dental implant attachments. Shear force was applied to determine the SBS of each material to denture acrylic resin. The difference between SBSs of polymethyl methacrylate and UBAR (claimed to bond to metal) to metal housings was also evaluated. There were no statistically significant differences among the SBSs of Jet Denture Repair Acrylic, EZ PickUp, and UBAR, but Quick Up had an SBS that was significantly lower than that of the other 3 materials. In addition, UBAR had a higher SBS to metal housings than did processed polymethyl methacrylate. PMID- 27367634 TI - Do we need keratinized mucosa for a healthy peri-implant soft tissue? AB - The presence of keratinized mucosa plays a fundamental role in peri-implant soft tissue health. This study assessed the impact of the width of keratinized mucosa (WKM) on peri-implant soft tissue parameters. A cross-sectional study was conducted on 110 bone-level implants in 36 patients. A minimum of 6 months had passed since the loading of implants, and the patients had at least 1 implant in 1 quadrant at the molar or premolar site restored with a single crown or fixed partial denture. The health of peri-implant soft tissue was assessed with a modified bleeding index (MBI), modified plaque index (MPI), and modified gingival index (MGI). Probing depth (PD), gingival recession (GR), and WKM were also measured. History of smoking and oral hygiene methods were recorded. A significant inverse correlation existed between WKM and the parameters MBI, MPI, MGI, and GR (P < 0.05). Values of MBI, MPI, MGI, and GR were significantly lower in areas with WKM >= 2 mm and higher in areas with WKM < 2 mm (P < 0.05). The WKM was greatest in subjects using the vibratory toothbrushing technique and narrowest in those using the horizontal toothbrushing technique (P < 0.05). The mean WKM was significantly greater in smokers than in nonsmokers (P < 0.05). Results of this study indicate that an association exists between WKM and peri implant soft tissue health. A minimum of 2 mm of keratinized mucosa around implants is recommended. PMID- 27367635 TI - The effect of preheating and opacity on the sorption and solubility of a composite resin. AB - This study evaluated the influence of material opacity and preheating on the sorption and solubility of a composite resin material. A commercially available composite resin and an 8 * 2-mm circular metallic matrix were used to fabricate a total of 60 specimens in 6 shades, of which 3 had conventional opacity (CA2, CA3, and CA3.5) and 3 were opaque (OA2, OA3, and OA3.5). Specimens were prepared at a room temperature of 25 degrees C or preheated to 60 degrees C (n = 5 per shade at each temperature). The specimens were weighed 3 times: M1, dried for 24 hours at 37 degrees C; M2, stored for 7 days in 75% ethanol at 37 degrees C; and M3, dried for an additional 24 hours at 37 degrees C. The weights were used to calculate the sorption and solubility of the composite resin and were analyzed using 2-way analysis of variance and Tukey tests (alpha = 5%). Composite resin specimens heated at 60 degrees C yielded lower values of sorption and solubility than did specimens prepared at 25 degrees C (P < 0.05). The sorption and solubility of conventional and opaque composite shades were found to be similar (P > 0.05), except for shade CA2, which presented a greater mean solubility value than OA2 (P = 0.004). Therefore, preheating was beneficial, as it lowered both the sorption and solubility of the evaluated composite resin, but opacity had little effect on these properties. PMID- 27367636 TI - Risk-benefit assessment for antibiotic prophylaxis in asplenic dental patients. AB - A review of the published literature revealed that discourse on the topic of antibiotic prophylaxis guidelines for the asplenic dental patient is limited and that guidelines regarding this issue have not been updated for years. The review determined that the professional protocol for the treatment of asplenic dental patients has changed over the last 30 years, particularly with reference to adult patients. Furthermore, as dentists and physicians now understand that blood-borne bacteremias are produced from everyday occurrences such as chewing and toothbrushing, bacteremias secondary to dental procedures are no longer viewed as seriously as in the past; therefore, the guidelines for antibiotic prophylaxis have changed. Antibiotic prophylaxis is not routinely indicated prior to dental procedures for asplenic adult dental patients without risk factors. However, antibiotic prophylaxis should be considered for young children, immunocompromised patients with underlying causative disease, or any patient during the first 3 years after a splenectomy. PMID- 27367637 TI - Adopting caries risk assessment in all practice environments. AB - Caries management by risk assessment (CAMBRA) is an evidence-based model intended to provide dentists with a protocol for diagnosis, treatment, and prevention of caries by assessing and addressing a patient's overall oral health. The aim of this review was to examine the literature on CAMBRA to determine its efficacy. Clinical studies demonstrate that the CAMBRA approach is an effective concept that is both predictive of dental caries development and accurate in outlining appropriate treatment options and preventive strategies that can reduce the morbidity of this common disease process across all patient demographics. PMID- 27367638 TI - Management of progressive apical root resorption 13 years after dental trauma and primary endodontic treatment. AB - Many studies have focused on the search for a restorative material with good sealing properties and biocompatibility for treatment of teeth with open apices and necrotic pulps, which can result from periradicular disease and root resorption. Mineral trioxide aggregate (MTA) has exhibited promising clinical results in retrograde fillings and pulpotomies as well as for treatment of root perforations, root resorptions, incomplete root formations, and pulpal necrosis. This case report describes the management of a progressive apical root resorption in a previously traumatized tooth that had been endodontically treated. Five years of clinical and radiographic follow-up demonstrated the clinical efficacy of MTA in limiting the inflammatory resorptive process and promoting apexification and regeneration of periradicular tissue. PMID- 27367639 TI - Effect of surface treatments of porcelain on adhesion of Candida albicans. AB - Surface treatment of porcelain is required to minimize the adhesion of microorganisms to surfaces of the restoration. This study sought to assess the effects of 3 different porcelain surface treatments on adhesion of Candida albicans. This in vitro experimental study was conducted on 60 porcelain disks (10 * 3 mm) randomly divided into 4 groups of 15. The nonglazed group received no surface treatment; specimens in the other 3 groups were glazed in the furnace, overglazed with liquid glaze, or polished using a polishing kit. The specimens were washed, sterilized, and separately incubated with 350 uL of Candida albicans suspension for 24 hours. Specimens were then rinsed for 20 seconds and shaken in 1 mL of saline solution for 1 minute, and 20 uL of this suspension was cultured in a plate and incubated at 37 degrees C for 48 hours. Candida albicans colonies were counted to assess the number of microorganisms adhering to each disk. Data were analyzed with the Kruskal-Wallis test. Statistically significant differences were found among the 4 groups in terms of C albicans adherence (P = 0.001). The nonglazed porcelain had the highest and the overglazed porcelain had the lowest mean adherence value. No statistically significant difference was noted between glazed and polished specimens. Based on the obtained results, overglazing resulted in the least adhesion of C albicans, and polishing provided a surface as smooth as a glazed surface. PMID- 27367640 TI - Composite resin bond strength to caries-affected dentin contaminated with 3 different hemostatic agents. AB - Bonding of composite resins to sound and caries-affected dentin in cervical areas may necessitate the use of hemostatic agents to control sulcular fluid and hemorrhage. The aim of this in vitro study was to evaluate the bond strengths of a self-etching adhesive system to sound and caries-affected dentin after the use of 3 different hemostatic agents. Composite resin cylinders were bonded to 48 caries-affected and 48 sound dentin surfaces in 8 groups. Groups 1-4 utilized caries-affected dentin: group 1, uncontaminated control; 2, ViscoStat; 3, ViscoStat Clear; and 4, trichloroacetic acid (TCA). Groups 5-8 utilized sound dentin: group 5, uncontaminated control; 6, ViscoStat; 7, ViscoStat Clear; and 8, TCA. The hemostatic agents were applied for 2 minutes and rinsed. After 500 rounds of thermocycling, shear bond strength tests were carried out. Data were analyzed with 1- and 2-way analyses of variance, t test, and post hoc Tukey tests at a significance level of P < 0.05. Bond strength was significantly influenced by dentin type (F = 38.23; P = 0.0001) and hemostatic agent (F = 6.32; P = 0.001). Furthermore, groups 2 and 6 (ViscoStat) showed significantly lower bond strength values than the control groups (groups 1 and 5) in both affected and sound dentin (P = 0.043 and P = 0.009, respectively). Within the limitations of this study, the bond strength of composite resin to caries-affected dentin was significantly reduced compared to that with sound dentin. Among the studied hemostatic agents, ViscoStat resulted in a greater decrease in dentin bond strength. Contamination of both sound and caries-affected dentin with hemostatic agents decreased composite resin bond strength. Of the 3 hemostatic agents used, ViscoStat Clear appeared to have the least detrimental effect on bond strength. PMID- 27367641 TI - Effect of a dedicated oral care program on periodontal status of medically compromised patients at the Toronto Rehabilitation Institute Dental Clinic. AB - Medically compromised patients attending the dental clinic at the Toronto Rehabilitation Institute have considerable gingival inflammation and breath odor. The objective of this study was to evaluate the effect of toothbrushing on the periodontal status of these patients and to determine if there were any additional benefit in combining brushing with an application of an antibiotic rinse. During the first 7 days of the study, the teeth of 11 participants were brushed twice a day by a dental hygienist using a soft-bristle suction toothbrush without toothpaste. Soft interproximal brushes were used to clean interproximal surfaces from the facial aspect. During the second week, facial and interproximal cleaning were repeated in the same patients, but the toothbrush and interproximal brush were dipped in 10-mL of a solution consisting of water and 40 mg/mL of metronidazole with nystatin. Each patient underwent an oral examination and biofilm sampling at baseline, after brushing without toothpaste (week 1), and after brushing with antibiotic solution (week 2). After week 1, tissues improved substantially, and there was a notable change in the biofilm on the teeth. The addition of an antibiotic solution increased healing and resulted in a further decrease in oral biofilm. Medically compromised patients would benefit considerably from a treatment regimen of antibiotic solution to decrease oral infection followed by a daily oral care program of brushing and interdental cleaning to maintain healthy oral tissues. PMID- 27367643 TI - Rhodium-Catalyzed Interconversion of Quinolinyl Ketones with Boronic Acids via C C Bond Activation. AB - A rhodium-catalyzed cross-coupling of aryl and aliphatic quinolinyl ketones with boronic acids has been developed. Proceeding via quinoline-directed carbon-carbon sigma bond activation, the transformation demonstrates tolerance of a range of functional groups on both the ketone and aryl boronic acid substrates, providing good to excellent yields of the new ketones, particularly those containing electron-withdrawing substituents. Catalyst reactivity is dependent on quinolinyl ketone substrates, with alkyl ketones requiring Rh(PPh3)3Cl instead of the more reactive [Rh(C2H4)2Cl]2. With the use of K2CO3 as an additive, methyl boronic acid is also a competent substrate, giving rise to an unprecedented methylation technique. PMID- 27367642 TI - Dynamical characterization of inactivation path in voltage-gated Na(+) ion channel by non-equilibrium response spectroscopy. AB - Inactivation path of voltage gated sodium channel has been studied here under various voltage protocols as it is the main governing factor for the periodic occurrence and shape of the action potential. These voltage protocols actually serve as non-equilibrium response spectroscopic tools to study the ion channel in non-equilibrium environment. In contrast to a lot of effort in finding the crystal structure based molecular mechanism of closed-state(CSI) and open-state inactivation(OSI); here our approach is to understand the dynamical characterization of inactivation. The kinetic flux as well as energetic contribution of the closed and open- state inactivation path is compared here for voltage protocols, namely constant, pulsed and oscillating. The non-equilibrium thermodynamic quantities used in response to these voltage protocols serve as improved characterization tools for theoretical understanding which not only agrees with the previously known kinetic measurements but also predict the energetically optimum processes to sustain the auto-regulatory mechanism of action potential and the consequent inactivation steps needed. The time dependent voltage pattern governs the population of the conformational states which when couple with characteristic rate parameters, the CSI and OSI selectivity arise dynamically to control the inactivation path. Using constant, pulsed and continuous oscillating voltage protocols we have shown that during depolarization the OSI path is more favored path of inactivation however, in the hyper-polarized situation the CSI is favored. It is also shown that the re-factorisation of inactivated sodium channel to resting state occurs via CSI path. Here we have shown how the subtle energetic and entropic cost due to the change in the depolarization magnitude determines the optimum path of inactivation. It is shown that an efficient CSI and OSI dynamical profile in principle can characterize the open-state drug blocking phenomena. PMID- 27367644 TI - Characteristics of double care demanding patients in a mental health care setting and a nursing home setting: results from the SpeCIMeN study. AB - BACKGROUND: Older patients suffering from a combination of psychiatric disorders and physical illnesses and/or dementia are called Double Care Demanding patients (DCDs). Special wards for DCDs within Dutch nursing homes (NHs) and mental health care institutions (MHCIs) offer a unique opportunity to obtain insight into the characteristics and needs of this challenging population. METHODS: This observational cross-sectional study collected data from 163 DCDs admitted to either a NH or a MHCI providing specialized care for DCDs. Similarities and differences between both DCD groups are described. RESULTS: Neuropsychiatric symptoms were highly prevalent in all DCDs but significantly more in MHCI-DCDs. Cognitive disorders were far more present in NH-DCDs, while MHCI-DCDs often suffered from multiple psychiatric disorders. The severity of comorbidities and care dependency were equally high among all DCDs. NH-DCDs expressed more satisfaction in overall quality of life. CONCLUSIONS: The institutionalized elderly DCD population is very heterogeneous. Specific care arrangements are necessary because the severity of a patient's physical illness and the level of functional impairment seem to be equally important as the patient's behavioural, psychiatric and social problems. Further research should assess the adequacy of the setting assignment and the professional skills needed to provide adequate care for elderly DCDs. PMID- 27367645 TI - Prediction of pathological stage based on clinical stage, serum prostate-specific antigen, and biopsy Gleason score: Partin Tables in the contemporary era. AB - OBJECTIVE: To update the Partin Tables for prediction of pathological stage in the contemporary setting and examine trends in patients treated with radical prostatectomy (RP) over the past three decades. PATIENTS AND METHODS: From January 2010 to October 2015, 4459 men meeting inclusion criteria underwent RP and pelvic lymphadenectomy for histologically confirmed prostate cancer at the Johns Hopkins Hospital. Preoperative clinical stage, serum prostate-specific antigen (PSA) level, and biopsy Gleason score (i.e. prognostic Grade Group) were used in a polychotomous logistic regression model to predict the probability of pathological outcomes categorised as: organ-confined (OC), extraprostatic extension (EPE), seminal vesicle involvement (SV+), or lymph node involvement (LN+). Preoperative characteristics and pathological findings in men treated with RP since 1983 were collected and clinical-pathological trends were described. RESULTS: The median (range) age at surgery was 60 (34-77) years and the median (range) PSA level was 4.9 (0.1-125.0) ng/mL. The observed probabilities of pathological outcomes were: OC disease in 74%, EPE in 20%, SV+ in 4%, and LN+ in 2%. The probability of EPE increased substantially when biopsy Gleason score increased from 6 (Grade Group 1, GG1) to 3 + 4 (GG2), with smaller increases for higher grades. The probability of LN+ was substantially higher for biopsy Gleason score 9-10 (GG5) as compared to lower Gleason scores. Area under the receiver operating characteristic curves for binary logistic models predicting EPE, SV+, and LN+ vs OC were 0.724, 0.856, and 0.918, respectively. The proportion of men treated with biopsy Gleason score <=6 cancer (GG1) was 47%, representing a substantial decrease from 63% in the previous cohort and 77% in 2000-2005. The proportion of men with OC cancer has remained similar during that time, equalling 73-74% overall. The proportions of men with SV+ (4.1% from 3.4%) and LN+ (2.3% from 1.4%) increased relative to the preceding era for the first time since the Partin Tables were introduced in 1993. CONCLUSIONS: The Partin Tables remain a straightforward and accurate approach for projecting pathological outcomes based on readily available clinical data. Acknowledging these data are derived from a tertiary care referral centre, the proportion of men with OC disease has remained stable since 2000, despite a substantial decline in the proportion of men with biopsy Gleason score 6 (GG1). This is consistent with the notion that many men with Gleason score 6 (GG1) disease were over treated in previous eras. PMID- 27367647 TI - Corrigendum. PMID- 27367646 TI - Repeated nationwide point-prevalence surveys of antimicrobial use in Swedish hospitals: data for actions 2003-2010. AB - This study sought to analyse antimicrobial pressure, indications for treatment, and compliance with treatment recommendations and to identify possible problem areas where inappropriate use could be improved through interventions by the network of the local Swedish Strategic Programme Against Antibiotic Resistance (Strama) groups. Five point-prevalence surveys were performed in between 49 and 72 participating hospitals from 2003 to 2010. Treatments were recorded for 19 predefined diagnosis groups and whether they were for community-acquired infection, hospital-acquired infection, or prophylaxis. Approximately one-third of inpatients were treated with antimicrobials. Compliance with guidelines for treatment of community-acquired pneumonia with narrow-spectrum penicillin was 17.0% during baseline 2003-2004, and significantly improved to 24.2% in 2010. Corresponding figures for quinolone use in uncomplicated cystitis in women were 28.5% in 2003-2004, and significantly improved, decreasing to 15.3% in 2010. The length of surgical prophylaxis improved significantly when data for a single dose and 1 day were combined, from 56.3% in 2003-2004 to 66.6% in 2010. Improved compliance was possibly the effect of active local feedback, repeated surveys, and increasing awareness of antimicrobial resistance. Strama groups are important for successful local implementation of antimicrobial stewardship programs in Sweden. PMID- 27367648 TI - Pitfalls in the identification of Enterococcus species and the detection of vanA and vanB genes. AB - The aims were to assess the performance of Vitek 2 in identifying enterococcal species and the implementation of GeneXpert((r)) vanA/vanB PCR for the detection of vancomycin-resistant enterococci (VRE). Gram-positive cocci from clinical and environmental specimens (n = 431) suspicious of being enterococci by conventional methods were evaluated by Vitek 2. This system identified 296 Enterococcus faecium, 87 Enterococcus faecalis, 10 Enterococcus villorum, 9 Enterococcus gallinarum, 9 Enterococcus durans, 5 Enterococcus casseliflavus, 1 Enterococcus spp. and 14 isolates as Non-Enterococcus. All strains were submitted to pulsed field gel electrophoresis (PFGE) analysis showing 64 banding patterns. Representative strains from each banding pattern were further characterized to species level by 16S rDNA sequencing. The misidentification rate by Vitek 2 to species level among 429 molecularly identified enterococci was 6% (26 isolates). Additionally, 372 rectal swabs were obtained from critically ill patients. They were evaluated for the presence of VRE by ChromID VRE combined with in-house PCR vs GeneXpert((r)) . GeneXpert((r)) showed high (>92%) sensitivity, specificity, accuracy for vanA-positive Enterococcus detection, as well as, sensitivity and specificity for vanB-positive strains. Positive predictive value for detection of vanB-positive enterococci by GeneXpert((r)) vanA/vanB was low (30%). GeneXpert((r)) showed the same efficacy as ChromID VRE in detecting vanA-positive enterococci, but lower for vanB-gene detection. SIGNIFICANCE AND IMPACT OF THE STUDY: The study shows that even though the performance of Vitek 2 Advanced Expert System was good in identifying enterococci to species level, it is important to verify results by a molecular method when phenotypic findings are discordant with epidemiologic patterns. Furthermore, GeneXpert((r)) vanA/vanB PCR and ChromID VRE combined with in-house PCR were applied in rectal samples for the detection of VRE colonization among critically ill patients. GeneXpert((r)) showed an excellent performance in detecting vanA-positive enterococci, but false positive results for vanB-gene detection render its application problematic in departments with high incidence of vanB-positive enterococci. PMID- 27367649 TI - Extending Corticostriatal Systems. PMID- 27367651 TI - Relationship between peak spatial-averaged specific absorption rate and peak temperature elevation in human head in frequency range of 1-30 GHz. AB - This study investigates the relationship between the peak temperature elevation and the peak specific absorption rate (SAR) averaged over 10 g of tissue in human head models in the frequency range of 1-30 GHz. As a wave source, a half-wave dipole antenna resonant at the respective frequencies is located in the proximity of the pinna. The bioheat equation is used to evaluate the temperature elevation by employing the SAR, which is computed by electromagnetic analysis, as a heat source. The computed SAR is post-processed by calculating the peak spatial averaged SAR with six averaging algorithms that consider different descriptions provided in international guidelines and standards, e.g. the number of tissues allowed in the averaging volume, different averaging shapes, and the consideration of the pinna. The computational results show that the SAR averaging algorithms excluding the pinna are essential when correlating the peak temperature elevation in the head excluding the pinna. In the averaging scheme considering an arbitrary shape, for better correlation, multiple tissues should be included in the averaging volume rather than a single tissue. For frequencies higher than 3-4 GHz, the correlation for peak temperature elevation in the head excluding the pinna is modest for the different algorithms. The 95th percentile value of the heating factor as well as the mean and median values derived here would be helpful for estimating the possible temperature elevation in the head. PMID- 27367650 TI - Regulatory Implications of Structural Changes in Tyr201 of the Oxygen Sensor Protein FixL. AB - FixL is a heme-based oxygen-sensing histidine kinase that induces the expression of nitrogen fixation genes under hypoxic conditions. Oxygen dissociation from heme iron in the sensor domain of FixL initiates protein conformational changes that are transmitted to the histidine kinase domain, activating autophosphorylation activity. Conversely, oxygen binding inhibits FixL kinase activity. It is essential to elucidate the changes that occur in the protein structure upon this oxygen dissociation for understanding of the allosteric transduction mechanism. We measured ultraviolet resonance Raman spectra of FixL and its mutants for deoxy, oxy, and carbonmonoxy forms to examine the changes in protein structure upon oxygen dissociation. The observed spectral changes indicated that Tyr201 and its neighboring residues undergo structural changes upon oxygen dissociation. Kinase assays showed that substitution of Tyr201 significantly decreased the inhibition of kinase activity upon oxygen binding. These data mean that weakening of the hydrogen bond of Tyr201 that is induced by oxygen dissociation is essential for inhibition of kinase activity. We also observed spectral changes in Tyr residues in the kinase domain upon oxygen dissociation from FixL, which is the first observation of oxygen-dependent structural changes in the kinase domain of FixL. The observed structural changes support the allosteric transduction pathway of FixL which we proposed previously [ Yano, S., Ishikawa, H., Mizuno, M., Nakamura, H., Shiro, Y., and Mizutani, Y. ( 2013 ) J. Phys. Chem. B 117 , 15786 - 15791 ]. PMID- 27367652 TI - Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1). AB - Bladder cancer is one of the most frequent cancers among males, and its poor survival rate reflects problems with aggressiveness and chemo-resistance. Recent interest has focused on the use of chemopreventatives (nontoxic natural agents that may suppress cancer progression) to induce targeted apoptosis for cancer therapy. Capsaicin, which has anti-cancer properties, is one such agent. It is known to preferentially inhibit a tumor-associated NADH oxidase (tNOX) that is preferentially expressed in cancer/transformed cells. Here, we set out to elucidate the correlation between tNOX expression and the inhibitory effects of capsaicin in human bladder cancer cells. We showed that capsaicin downregulates tNOX expression and decreases bladder cancer cell growth by enhancing apoptosis. Moreover, capsaicin was found to reduce the expression levels of several proteins involved in cell cycle progression, in association with increases in the cell doubling time and enhanced cell cycle arrest. Capsaicin was also shown to inhibit the activation of ERK, thereby reducing the phosphorylation of paxillin and FAK, which leads to decreased cell migration. Finally, our results indicate that RNA interference-mediated tNOX depletion enhances spontaneous apoptosis, prolongs cell cycle progression, and reduces cell migration and the epithelial-mesenchymal transition. We also observed a downregulation of sirtuin 1 (SIRT1) in these tNOX knockdown cells, a deacetylase that is important in multiple cellular functions. Taken together, our results indicate that capsaicin inhibits the growth of bladder cancer cells by inhibiting tNOX and SIRT1 and thereby reducing proliferation, attenuating migration, and prolonging cell cycle progression. PMID- 27367653 TI - Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses. AB - In this review, we discuss the importance of capsaicin to the current understanding of neuronal modulation of pain and explore the mechanisms of capsaicin-induced pain. We will focus on the analgesic effects of capsaicin and its clinical applicability in treating pain. Furthermore, we will draw attention to the rationale for other clinical therapeutic uses and implications of capsaicin in diseases such as obesity, diabetes, cardiovascular conditions, cancer, airway diseases, itch, gastric, and urological disorders. PMID- 27367655 TI - Special Issue "Membrane Catalysis". AB - Membrane technology is recognized as a scientific sector of multidisciplinary interest.[...]. PMID- 27367654 TI - Relevance of the Pharmacokinetic and Pharmacodynamic Profiles of Puerariae lobatae Radix to Aggregation of Multi-Component Molecules in Aqueous Decoctions. AB - The complexity of traditional Chinese medicines (TCMs) is related to their multi component system. TCM aqueous decoction is a common clinical oral formulation. Between molecules in solution, there exist intermolecular strong interactions to form chemical bonds or weak non-bonding interactions such as hydrogen bonds and Van der Waals forces, which hold molecules together to form "molecular aggregates". Taking the TCM Puerariae lobatae Radix (Gegen) as an example, we explored four Gegen decoctions of different concentration of 0.019, 0.038, 0.075, and 0.30 g/mL, named G-1, G-2, G-3, and G-4. In order of molecular aggregate size (diameter) the four kinds of solution were ranked G-1 < G-2 < G-3 < G-4 by Flow Cell 200S IPAC image analysis. A rabbit vertebrobasilar artery insufficiency (VBI) model was set up and they were given Gegen decoction (GGD) at a clinical dosage of 0.82 g/kg (achieved by adjusting the gastric perfusion volume depending on the concentration). The HPLC fingerprint of rabbit plasma showed that the chemical component absorption into blood in order of peak area values was G-1 < G 2 > G-3 > G-4. Puerarin and daidzin are the major constituents of Gegen, and the pharmacokinetics of G-1 and G-2 puerarin conformed with the two compartment open model, while for G-3 and G-4, they conformed to a one compartment open model. For all four GGDs the pharmacokinetics of daidzin complied with a one compartment open model. FQ-PCR assays of rabbits' vertebrobasilar arterial tissue were performed to determine the pharmacodynamic profiles of the four GGDs. GGD markedly lowered the level of AT1R mRNA, while the AT2R mRNA level was increased significantly vs. the VBI model, and G-2 was the most effective. In theory the dosage was equal to the blood drug concentration and should be consistent; however, the formation of molecular aggregates affects drug absorption and metabolism, and therefore influences drugs' effects. Our data provided references for the rational use of Chinese medicines in the clinic, such as the best oral preparation and decoction concentration. PMID- 27367656 TI - Quality Evaluation of Scrophulariae Radix Processed by Different 'Sweating' Methods Based on Simultaneous Determination of Multiple Bioactive Constituents Combined with Grey Relational Analysis. AB - Scrophulariae Radix is one of the most popular traditional Chinese medicines (TCMs), which needs to be processed by 'sweating' methods. Primary processing of Scrophulariae Radix is an important link which closely relates to the quality of products in this TCM. To facilitate selection of the suitable 'sweating' processing method for Scrophulariae Radix, in this study the quality of Scrophulariae Radix processed by different 'sweating' methods was evaluated based on simultaneous determination of multiple bioactive constituents combined with grey relational analysis. The contents of iridoid glycosides, phenylpropanoid glycosides, and organic acids in Scrophulariae Radix processed by different 'sweating' methods were simultaneously determined using ultra high performance liquid chromatography coupled with triple quadrupole-linear ion trap mass spectrometry (UPLC-QTRAP-MS/MS). Furthermore, grey relational analysis (GRA) was performed to evaluate the 'sweating' processed samples according to the contents of twelve constituents. All of the results demonstrated that the quality of Scrophulariae Radix processed by oven drying at 35 degrees C and 'sweating' for three days was better. The developed method was useful for the overall assessment on quality of Scrophulariae Radix, and this study may provide the foundation and support for 'sweating' processing of Scrophulariae Radix in normalization and standardization. PMID- 27367657 TI - The Effects and Mechanisms of Periplaneta americana Extract Reversal of Multi Drug Resistance in BEL-7402/5-FU Cells. AB - The present study reports the reversing effects of extracts from P. americana on multidrug resistance of BEL-7402/5-FU cells, as well as a preliminary investigation on their mechanism of action. A methylthiazolyl tetrazolium (MTT) method was applied to determine the multidrug resistance of BEL-7402/5-FU, while an intracellular drug accumulation assay was used to evaluate the effects of a column chromatography extract (PACC) and defatted extract (PADF) from P. americana on reversing multi-drug resistance. BEL-7402/5-FU reflected high resistance to 5-FU; PACC and PADF could promote drug accumulation in BEL-7402/5 FU cells, among which PADF was more effective than PACC. Moreover, results from the immunocytochemical method showed that PACC and PADF could downregulate the expression of drug resistance-associated proteins (P-gp, MRP, LRP); PACC and PADF had no effects on the expression of multidrug resistance-associated enzymes (GST pi), but PACC could increase the expression of multidrug resistance-associated enzymes (PKC). Results of real-time fluorescence quantitative PCR revealed that PACC and PADF were able to markedly inhibit the expression of multidrug resistance-associated genes (MDR1, LRP and MRP1); PACC presented a significant impact on the gene expression of multidrug resistance-associated enzymes, which increased the gene expression of GST-pi and PKC. However, PADF had little impact on the expression of multidrug resistance-associated enzymes. These results demonstrated that PACC and PADF extracted from P. americana could effectively reverse MDR in BEL-7402/5-FU cells, whose mechanism was to inhibit the expression of P-gp, MRP, and LRP, and that PADF was more effective in the reversal of MDR than did PACC. In addition, some of extracts from P. americana altered (sometimes increasing) the expression of multidrug resistance-associated enzymes. PMID- 27367658 TI - Rational Design and Synthesis of New, High Efficiency, Multipotent Schiff Base 1,2,4-triazole Antioxidants Bearing Butylated Hydroxytoluene Moieties. AB - A new series of multipotent antioxidants (MPAOs), namely Schiff base-1,2,4 triazoles attached to the oxygen-derived free radical scavenging moiety butylated hydroxytoluene (BHT) were designed and subsequently synthesized. The structure activity relationship (SAR) of the designed antioxidants was established alongside the prediction of activity spectra for substances (PASS). The antioxidant activities of the synthesized compounds 4-10 were tested by the DPPH bioassay. The synthesized compounds 4-10 inhibited stable DPPH free radicals at a level that is 10(-4) M more than the well-known standard antioxidant BHT. Compounds 8-10 with para-substituents were less active than compounds 4 and 5 with trimethoxy substituents compared to those with a second BHT moiety (compounds 6 and 7). With an IC50 of 46.13 +/- 0.31 uM, compound 6 exhibited the most promising in vitro inhibition at 89%. Therefore, novel MPAOs containing active triazole rings, thioethers, Schiff bases, and BHT moieties are suggested as potential antioxidants for inhibiting oxidative stress processes and scavenging free radicals, hence, this combination of functions is anticipated to play a vital role in repairing cellular damage, preventing various human diseases and in medical therapeutic applications. PMID- 27367659 TI - Dyeing of Polyester with Disperse Dyes: Part 2. Synthesis and Dyeing Characteristics of Some Azo Disperse Dyes for Polyester Fabrics. AB - The goal of this study was to utilize carrier for accelerating the rate of dyeing not only to enhance dyeing of polyester fabrics dyed with disperse dyes 3a,b, but also to save energy. Both the color strength expressed as dye uptake and the fastness properties of the dyed fabrics were evaluated. PMID- 27367660 TI - In Silico Mining for Antimalarial Structure-Activity Knowledge and Discovery of Novel Antimalarial Curcuminoids. AB - Malaria is a parasitic tropical disease that kills around 600,000 patients every year. The emergence of resistant Plasmodium falciparum parasites to artemisinin based combination therapies (ACTs) represents a significant public health threat, indicating the urgent need for new effective compounds to reverse ACT resistance and cure the disease. For this, extensive curation and homogenization of experimental anti-Plasmodium screening data from both in-house and ChEMBL sources were conducted. As a result, a coherent strategy was established that allowed compiling coherent training sets that associate compound structures to the respective antimalarial activity measurements. Seventeen of these training sets led to the successful generation of classification models discriminating whether a compound has a significant probability to be active under the specific conditions of the antimalarial test associated with each set. These models were used in consensus prediction of the most likely active from a series of curcuminoids available in-house. Positive predictions together with a few predicted as inactive were then submitted to experimental in vitro antimalarial testing. A large majority from predicted compounds showed antimalarial activity, but not those predicted as inactive, thus experimentally validating the in silico screening approach. The herein proposed consensus machine learning approach showed its potential to reduce the cost and duration of antimalarial drug discovery. PMID- 27367661 TI - Ultrasonic Synthesis, Molecular Structure and Mechanistic Study of 1,3-Dipolar Cycloaddition Reaction of 1-Alkynylpyridinium-3-olate and Acetylene Derivatives. AB - Regioselectively, ethyl propiolate reacted with 1-(propergyl)-pyridinium-3-olate to give two regioisomers; ethyl 4-oxo-8-(prop-2-ynyl)-8-aza-bicyclo(3.2.1)octa 2,6-diene-6-carboxylate 4, ethyl 2-oxo-8-(prop-2-ynyl)-8-aza-bicyclo(3.2.1)octa 3,6-diene-6-carboxylate 5 as well as ethyl 2,6-dihydro-6-(prop-2-ynyl)furo(2,3 c)pyridine-3-carboxylate 6. The obtained compounds were identified by their spectral (IR, mass and NMR) data. Moreover, DFT quantum chemical calculations were used to study the mechanism of the cycloaddition reaction. The regioselectivity was explained using transition state calculations, where the calculations agreed with the formation of products 4 and 5 in almost the same ratio. The reaction was also extended for diphenylaceylene as dipolarophile to give only two products instead of three. PMID- 27367662 TI - Artonin E and Structural Analogs from Artocarpus Species Abrogates Estrogen Receptor Signaling in Breast Cancer. AB - The increasing rate of mortality ensued from breast cancer has encouraged research into safer and efficient therapy. The human Estrogen receptor alpha has been implicated in the majority of reported breast cancer cases. Molecular docking employing Glide, Schrodinger suite 2015, was used to study the binding affinities of small molecules from the Artocarpus species after their drug-like properties were ascertained. The structure of the ligand-binding domain of human Estrogen receptor alpha was retrieved from Protein Data Bank while the structures of compounds were collected from PubChem database. The binding interactions of the studied compounds were reported as well as their glide scores. The best glide scored ligand, was Artonin E with a score of -12.72 Kcal when compared to other studied phytomolecules and it evoked growth inhibition of an estrogen receptor positive breast cancer cells in submicromolar concentration (3.8-6.9 uM) in comparison to a reference standard Tamoxifen (18.9-24.1 uM) within the tested time point (24-72 h). The studied ligands, which had good interactions with the target receptor, were also drug-like when compared with 95% of orally available drugs with the exception of Artoelastin, whose predicted physicochemical properties rendered it less drug-like. The in silico physicochemical properties, docking interactions and growth inhibition of the best glide scorer are indications of the anti-breast cancer relevance of the studied molecules. PMID- 27367663 TI - Molecular Dynamics Simulations to Investigate the Binding Mode of the Natural Product Liphagal with Phosphoinositide 3-Kinase alpha. AB - Phosphatidylinositol 3-kinase alpha (PI3Kalpha) is an attractive target for anticancer drug design. Liphagal, isolated from the marine sponge Aka coralliphaga, possesses the special "liphagane" meroterpenoid carbon skeleton and has been demonstrated as a PI3Kalpha inhibitor. Molecular docking and molecular dynamics simulations were performed to explore the dynamic behaviors of PI3Kalpha binding with liphagal, and free energy calculations and energy decomposition analysis were carried out by use of molecular mechanics/Poisson-Boltzmann (generalized Born) surface area (MM/PB(GB)SA) methods. The results reveal that the heteroatom rich aromatic D-ring of liphagal extends towards the polar region of the binding site, and the D-ring 15-hydroxyl and 16-hydroxyl form three hydrogen bonds with Asp810 and Tyr836. The cyclohexyl A-ring projects up into the upper pocket of the lipophilic region, and the hydrophobic/van der Waals interactions with the residues Met772, Trp780, Ile800, Ile848, Val850, Met922, Phe930, Ile932 could be the key interactions for the affinity of liphagal to PI3Kalpha. Thus, a new strategy for the rational design of more potent analogs of liphagal against PI3Kalpha is provided. Our proposed PI3Kalpha/liphagal binding mode would be beneficial for the discovery of new active analogs of liphagal against PI3Kalpha. PMID- 27367664 TI - Alendronate-Loaded Modified Drug Delivery Lipid Particles Intended for Improved Oral and Topical Administration. AB - The present paper focuses on solid lipid particles (SLPs), described in the literature as the most effective lipid drug delivery systems that have been introduced in the last decades, as they actually combine the advantages of polymeric particles, hydrophilic/lipophilic emulsions and liposomes. In the current study, we present our most recent advances in the preparation of alendronate (AL)-loaded SLPs prepared by hot homogenization and ultrasonication using various ratios of a self-emulsifying lipidic mixture of Compritol 888, Gelucire 44/14, and Cremophor A 25. The prepared AL-loaded SLPs were investigated for their physicochemical, morphological and structural characteristics by dynamic light scattering, differential scanning calorimetry, thermogravimetric and powder X-ray diffraction analysis, infrared spectroscopy, optical and scanning electron microscopy. Entrapment efficacy and actual drug content were assessed by a validated HPLC method. In vitro dissolution tests performed in simulated gastro-intestinal fluids and phosphate buffer solution pH 7.4 revealed a prolonged release of AL of 70 h. Additionally, release kinetics analysis showed that both in simulated gastrointestinal fluids and in phosphate buffer solution, AL is released from SLPs based on equal ratios of lipid excipients following zero order kinetics, which characterizes prolonged-release drug systems. PMID- 27367665 TI - Study of the Activity and Possible Mechanism of Action of a Reversible Inhibitor of Recombinant Human KAT-2: A Promising Lead in Neurodegenerative and Cognitive Disorders. AB - Abnormal levels of kynurenic acid (KYNA) in the human brain are believed to be connected to several central nervous system (CNS) diseases, therefore compounds which affect the production of this crucial metabolite are of interest in CNS drug development. The majority of KYNA production is accounted for by kynurenine aminotransferase-2 (KAT-2) in the mammalian brain; hence this enzyme is one of the most interesting targets with which to modulate KYNA levels. Recently developed human KAT-2 inhibitors with high potencies are known to irreversibly bind to the enzyme cofactor, pyridoxal-5'-phosphate (PLP), which may lead to severe side effects due to the abundance of PLP-dependent enzymes. In this study, we report a reversible and competitive inhibitor of KAT-2. Its inhibitory activities were examined using HPLC and surface plasmon resonance (SPR) and compare favorably with other recently reported KAT-2 inhibitors. Our inhibitor, NS-1502, demonstrates suitable inhibitory activity, almost 10 times more potent than the known reversible KAT-2, (S)-ESBA. PMID- 27367666 TI - One Pot Selective Arylation of 2-Bromo-5-Chloro Thiophene; Molecular Structure Investigation via Density Functional Theory (DFT), X-ray Analysis, and Their Biological Activities. AB - Synthesis of 2,5-bisarylthiophenes was accomplished by sequential Suzuki cross coupling reaction of 2-bromo-5-chloro thiophenes. Density functional theory (DFT) studies were carried out at the B3LYP/6-31G(d, p) level of theory to compare the geometric parameters of 2,5-bisarylthiophenes with those from X-ray diffraction results. The synthesized compounds are screened for in vitro bacteria scavenging abilities. At the concentration of 50 and 100 MUg/mL, compounds 2b, 2c, 2d, 3c, and 3f with IC50-values of 51.4, 52.10, 58.0, 56.2, and 56.5 MUg/mL respectively, were found most potent against E. coli. Among all the synthesized compounds 2a, 2d, 3c, and 3e with the least values of IC50 77, 76.26, 79.13 MUg/mL respectively showed significant antioxidant activities. Almost all of the compounds showed good antibacterial activity against Escherichia coli, whereas 2-chloro-5-(4 methoxyphenyl) thiophene (2b) was found most active among all synthesized compound with an IC50 value of 51.4 MUg/mL. All of the synthesized compounds were screened for nitric oxide scavenging activity as well. Frontier molecular orbitals (FMOs) and molecular electrostatic potentials of the target compounds were also studied theoretically to account for their relative reactivity. PMID- 27367667 TI - Stable Isotope-Assisted Evaluation of Different Extraction Solvents for Untargeted Metabolomics of Plants. AB - The evaluation of extraction protocols for untargeted metabolomics approaches is still difficult. We have applied a novel stable isotope-assisted workflow for untargeted LC-HRMS-based plant metabolomics , which allows for the first time every detected feature to be considered for method evaluation. The efficiency and complementarity of commonly used extraction solvents, namely 1 + 3 (v/v) mixtures of water and selected organic solvents (methanol, acetonitrile or methanol/acetonitrile 1 + 1 (v/v)), with and without the addition of 0.1% (v/v) formic acid were compared. Four different wheat organs were sampled, extracted and analysed by LC-HRMS. Data evaluation was performed with the in-house developed MetExtract II software and R. With all tested solvents a total of 871 metabolites were extracted in ear, 785 in stem, 733 in leaf and 517 in root samples, respectively. Between 48% (stem) and 57% (ear) of the metabolites detected in a particular organ were found with all extraction mixtures, and 127 of 996 metabolites were consistently shared between all extraction agent/organ combinations. In aqueous methanol, acidification with formic acid led to pronounced pH dependency regarding the precision of metabolite abundance and the number of detectable metabolites, whereas extracts of acetonitrile-containing mixtures were less affected. Moreover, methanol and acetonitrile have been found to be complementary with respect to extraction efficiency. Interestingly, the beneficial properties of both solvents can be combined by the use of a water methanol-acetonitrile mixture for global metabolite extraction instead of aqueous methanol or aqueous acetonitrile alone. PMID- 27367668 TI - Mechanisms Underlying Activation of alpha1-Adrenergic Receptor-Induced Trafficking of AQP5 in Rat Parotid Acinar Cells under Isotonic or Hypotonic Conditions. AB - Defective cellular trafficking of aquaporin-5 (AQP5) to the apical plasma membrane (APM) in salivary glands is associated with the loss of salivary fluid secretion. To examine mechanisms of alpha1-adrenoceptor (AR)-induced trafficking of AQP5, immunoconfocal microscopy and Western blot analysis were used to analyze AQP5 localization in parotid tissues stimulated with phenylephrine under different osmolality. Phenylephrine-induced trafficking of AQP5 to the APM and lateral plasma membrane (LPM) was mediated via the alpha1A-AR subtype, but not the alpha1B- and alpha1D-AR subtypes. Phenylephrine-induced trafficking of AQP5 was inhibited by ODQ and KT5823, inhibitors of nitric oxide (NO)-stimulated guanylcyclase (GC) and protein kinase (PK) G, respectively, indicating the involvement of the NO/ soluble (c) GC/PKG signaling pathway. Under isotonic conditions, phenylephrine-induced trafficking was inhibited by La(3+), implying the participation of store-operated Ca(2+) channel. Under hypotonic conditions, phenylephrine-induced trafficking of AQP5 to the APM was higher than that under isotonic conditions. Under non-stimulated conditions, hypotonicity-induced trafficking of AQP5 to the APM was inhibited by ruthenium red and La(3+), suggesting the involvement of extracellular Ca(2+) entry. Thus, alpha1A-AR activation induced the trafficking of AQP5 to the APM and LPM via the Ca(2+)/ cyclic guanosine monophosphate (cGMP)/PKG signaling pathway, which is associated with store-operated Ca(2+) entry. PMID- 27367669 TI - A Homogeneous Polysaccharide from Fructus Schisandra chinensis (Turz.) Baill Induces Mitochondrial Apoptosis through the Hsp90/AKT Signalling Pathway in HepG2 Cells. AB - According to the potential anti-hepatoma therapeutic effect of Schisandra chinensis polysaccharides presented in previous studies, a bioactive constituent, homogeneous Schisandra chinensis polysaccharide-0-1 (SCP-0-1), molecular weight (MW) circa 69.980 kDa, was isolated and purified. We assessed the efficacy of SCP 0-1 against human hepatocellular liver carcinoma (HepG2) cells to investigate the effects of its antitumour activity and molecular mechanisms. Anticancer activity was evaluated using microscopy, 3-[4,5-dimethyl-2-thiazolyl]-2,5 diphenyltetrazolium bromide (MTT) assay, Hoechst 33258 staining, acridine orange (AO) staining, flow cytometry (FCM), and cell-cycle analysis. SCP-0-1 inhibited the HepG2 cells' growth via inducing apoptosis and second gap/mitosis (G2/M) arrest dose-dependently, with a half maximal inhibitory concentration (IC50) value of 479.63 ug/mL. Western blotting of key proteins revealed the apoptotic and autophagic potential of SCP-0-1. Besides, SCP-0-1 upregulated Bcl-2 Associated X Protein (Bax) and downregulated B-cell leukemia/lymphoma 2 (Bcl-2) in the HepG2 cells. The expression of caspase-3, -8, and -9; poly (ADP-ribose) polymerase (PARP); cytochrome c (Cyt C); tumor protein 53 (p53); survivin; sequestosome 1 (p62); microtubule-associated protein 1 light chain-3B (LC3B); mitogen-activated protein kinase p38 (p38); extracellular regulated protein kinases (ERK); c-Jun N-terminal kinase (JNK); protein kinase B (AKT); and heat shock protein 90 (Hsp90) were evaluated using Western blotting. Our findings demonstrate a novel mechanism through which SCP-0-1 exerts its antiproliferative activity and induces mitochondrial apoptosis rather than autophagy. The induction of mitochondrial apoptosis was attributed to the inhibition of the Hsp90/AKT signalling pathway in an extracellular signal-regulated kinase-independent manner. The results also provide initial evidence on a molecular basis that SCP-0 1 can be used as an anti-hepatocellular carcinoma therapeutic agent in the future. PMID- 27367670 TI - Computational Identification of the Paralogs and Orthologs of Human Cytochrome P450 Superfamily and the Implication in Drug Discovery. AB - The human cytochrome P450 (CYP) superfamily consisting of 57 functional genes is the most important group of Phase I drug metabolizing enzymes that oxidize a large number of xenobiotics and endogenous compounds, including therapeutic drugs and environmental toxicants. The CYP superfamily has been shown to expand itself through gene duplication, and some of them become pseudogenes due to gene mutations. Orthologs and paralogs are homologous genes resulting from speciation or duplication, respectively. To explore the evolutionary and functional relationships of human CYPs, we conducted this bioinformatic study to identify their corresponding paralogs, homologs, and orthologs. The functional implications and implications in drug discovery and evolutionary biology were then discussed. GeneCards and Ensembl were used to identify the paralogs of human CYPs. We have used a panel of online databases to identify the orthologs of human CYP genes: NCBI, Ensembl Compara, GeneCards, OMA ("Orthologous MAtrix") Browser, PATHER, TreeFam, EggNOG, and Roundup. The results show that each human CYP has various numbers of paralogs and orthologs using GeneCards and Ensembl. For example, the paralogs of CYP2A6 include CYP2A7, 2A13, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 2F1, 2J2, 2R1, 2S1, 2U1, and 2W1; CYP11A1 has 6 paralogs including CYP11B1, 11B2, 24A1, 27A1, 27B1, and 27C1; CYP51A1 has only three paralogs: CYP26A1, 26B1, and 26C1; while CYP20A1 has no paralog. The majority of human CYPs are well conserved from plants, amphibians, fishes, or mammals to humans due to their important functions in physiology and xenobiotic disposition. The data from different approaches are also cross-validated and validated when experimental data are available. These findings facilitate our understanding of the evolutionary relationships and functional implications of the human CYP superfamily in drug discovery. PMID- 27367671 TI - Fourier Transform Mass Spectrometry and Nuclear Magnetic Resonance Analysis for the Rapid and Accurate Characterization of Hexacosanoylceramide. AB - Ceramides are a central unit of all sphingolipids which have been identified as sites of biological recognition on cellular membranes mediating cell growth and differentiation. Several glycosphingolipids have been isolated, displaying immunomodulatory and anti-tumor activities. These molecules have generated considerable interest as potential vaccine adjuvants in humans. Accurate analyses of these and related sphingosine analogues are important for the characterization of structure, biological function, and metabolism. We report the complementary use of direct laser desorption ionization (DLDI), sheath flow electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) and high-field nuclear magnetic resonance (NMR) analysis for the rapid, accurate identification of hexacosanoylceramide and starting materials. DLDI does not require stringent sample preparation and yields representative ions. Sheath-flow ESI yields ions of the product and byproducts and was significantly better than monospray ESI due to improved compound solubility. Negative ion sheath flow ESI provided data of starting materials and products all in one acquisition as hexacosanoic acid does not ionize efficiently when ceramides are present. NMR provided characterization of these lipid molecules complementing the results obtained from MS analyses. NMR data was able to differentiate straight chain versus branched chain alkyl groups not easily obtained from mass spectrometry. PMID- 27367673 TI - The NAD-Dependent Deacetylase Sirtuin-1 Regulates the Expression of Osteogenic Transcriptional Activator Runt-Related Transcription Factor 2 (Runx2) and Production of Matrix Metalloproteinase (MMP)-13 in Chondrocytes in Osteoarthritis. AB - Aging is one of the major pathologic factors associated with osteoarthritis (OA). Recently, numerous reports have demonstrated the impact of sirtuin-1 (Sirt1), which is the NAD-dependent deacetylase, on human aging. It has been demonstrated that Sirt1 induces osteogenic and chondrogenic differentiation of mesenchymal stem cells. However, the role of Sirt1 in the OA chondrocytes still remains unknown. We postulated that Sirt1 regulates a hypertrophic chondrocyte lineage and degeneration of articular cartilage through the activation of osteogenic transcriptional activator Runx2 and matrix metalloproteinase (MMP)-13 in OA chondrocytes. To verify whether sirtuin-1 (Sirt1) regulates chondrocyte activity in OA, we studied expressions of Sirt1, Runx2 and production of MMP-13, and their associations in human OA chondrocytes. The expression of Sirt1 was ubiquitously observed in osteoarthritic chondrocytes; in contrast, Runx2 expressed in the osteophyte region in patients with OA and OA model mice. OA relating catabolic factor IL-1betaincreased the expression of Runx2 in OA chondrocytes. OA chondrocytes, which were pretreated with Sirt1 inhibitor, inhibited the IL-1beta induced expression of Runx2 compared to the control. Since the Runx2 is a promotor of MMP-13 expression, Sirt1 inactivation may inhibit the Runx2 expression and the resultant down-regulation of MMP-13 production in chondrocytes. Our findings suggest thatSirt1 may regulate the expression of Runx2, which is the osteogenic transcription factor, and the production of MMP-13 from chondrocytes in OA. Since Sirt1 activity is known to be affected by several stresses, including inflammation and oxidative stress, as well as aging, SIRT may be involved in the development of OA. PMID- 27367672 TI - Structure and Functional Diversity of GCN5-Related N-Acetyltransferases (GNAT). AB - General control non-repressible 5 (GCN5)-related N-acetyltransferases (GNAT) catalyze the transfer of an acyl moiety from acyl coenzyme A (acyl-CoA) to a diverse group of substrates and are widely distributed in all domains of life. This review of the currently available data acquired on GNAT enzymes by a combination of structural, mutagenesis and kinetic methods summarizes the key similarities and differences between several distinctly different families within the GNAT superfamily, with an emphasis on the mechanistic insights obtained from the analysis of the complexes with substrates or inhibitors. It discusses the structural basis for the common acetyltransferase mechanism, outlines the factors important for the substrate recognition, and describes the mechanism of action of inhibitors of these enzymes. It is anticipated that understanding of the structural basis behind the reaction and substrate specificity of the enzymes from this superfamily can be exploited in the development of novel therapeutics to treat human diseases and combat emerging multidrug-resistant microbial infections. PMID- 27367674 TI - CD133 Modulate HIF-1alpha Expression under Hypoxia in EMT Phenotype Pancreatic Cancer Stem-Like Cells. AB - Although CD133 is a known representative cancer stem cell marker, its function in tumor aggressiveness under hypoxia is not fully known. The aim of this study is to demonstrate that CD133 regulates hypoxia inducible factor (HIF)-1alpha expression with tumor migration. The CD133+ pancreatic cancer cell line, Capan1M9, was compared with the CD133(-) cell line, shCD133M9, under hypoxia. HIF 1alpha expression levels were compared by Western blot, HIF-1alpha nucleus translocation assay and real-time (RT)-PCR. The hypoxia responsive element (HRE) was observed by luciferase assay. The migration ability was analyzed by migration and wound healing assays. Epithelial mesenchymal transition (EMT) related genes were analyzed by real-time RT-PCR. HIF-1alpha was highly expressed in Capan1M9 compared to shCD133M9 under hypoxia because of the high activation of HRE. Furthermore, the migration ability of Capan1M9 was higher than that of shCD133M9 under hypoxia, suggesting higher expression of EMT related genes in Capan1M9 compared to shCD133M9. CONCLUSION: HIF-1alpha expression under hypoxia in CD133+ pancreatic cancer cells correlated with tumor cell migration through EMT gene expression. Understanding the function of CD133 in cancer aggressiveness provides a novel therapeutic approach to eradicate pancreatic cancer stem cells. PMID- 27367675 TI - Novel Hybrid Peptide Cecropin A (1-8)-LL37 (17-30) with Potential Antibacterial Activity. AB - Hybridizing different antimicrobial peptides (AMPs) is a particularly successful approach to obtain novel AMPs with increased antimicrobial activity but minimized cytotoxicity. The hybrid peptide cecropin A (1-8)-LL37 (17-30) (C-L) combining the hydrophobic N-terminal fragment of cecropin A (C) with the core antimicrobial fragment of LL37 (L) was designed and synthesized. C-L showed higher antibacterial activity against all indicator strains than C and L, and no hemolytic activity to sheep erythrocytes was observed. C-L kills bacterial cells and causes disruption of surface structure, as determined by scanning electron microscopy. Synergistic effects were observed in the combination of C-L with several antibiotics (chloramphenicol, thiamphenicol, or neomycin sulfate) against Escherichia coli and Staphylococcus aureus. PMID- 27367676 TI - Modulation of PPAR Expression and Activity in Response to Polyphenolic Compounds in High Fat Diets. AB - Peroxisome proliferator-activated receptors (PPAR) are transcription factors that modulate energy metabolism in liver, adipose tissue and muscle. High fat diets (HFD) can negatively impact PPAR expression or activity, favoring obesity, dyslipidemia, insulin resistance and other conditions. However, polyphenols (PP) found in vegetable foodstuffs are capable of positively modulating this pathway. We therefore focused this review on the possible effects that PP can have on PPAR when administered together with HFD. We found that PP from diverse sources, such as coffee, olives, rice, berries and others, are capable of inducing the expression of genes involved in a decrease of adipose mass, liver and serum lipids and lipid biosynthesis in animal and cell models of HFD. Since cells or gut bacteria can transform PP into different metabolites, it is possible that a synergistic or antagonistic effect ultimately occurs. PP molecules from vegetable sources are an interesting option to maintain or return to a state of energy homeostasis, possibly due to an adequate PPAR expression and activity. PMID- 27367677 TI - Subinhibitory Concentrations of Allicin Decrease Uropathogenic Escherichia coli (UPEC) Biofilm Formation, Adhesion Ability, and Swimming Motility. AB - Uropathogenic Escherichia coli (UPEC) biofilm formation enables the organism to avoid the host immune system, resist antibiotics, and provide a reservoir for persistent infection. Once the biofilm is established, eradication of the infection becomes difficult. Therefore, strategies against UPEC biofilm are urgently required. In this study, we investigated the effect of allicin, isolated from garlic essential oil, on UPEC CFT073 and J96 biofilm formation and dispersal, along with its effect on UPEC adhesion ability and swimming motility. Sub-inhibitory concentrations (sub-MICs) of allicin decreased UPEC biofilm formation and affected its architecture. Allicin was also capable of dispersing biofilm. Furthermore, allicin decreased the bacterial adhesion ability and swimming motility, which are important for biofilm formation. Real-time quantitative polymerase chain reaction (RT-qPCR) revealed that allicin decreased the expression of UPEC type 1 fimbriae adhesin gene fimH. Docking studies suggested that allicin was located within the binding pocket of heptyl alpha-d mannopyrannoside in FimH and formed hydrogen bonds with Phe1 and Asn135. In addition, allicin decreased the expression of the two-component regulatory systems (TCSs) cognate response regulator gene uvrY and increased the expression of the RNA binding global regulatory protein gene csrA of UPEC CFT073, which is associated with UPEC biofilm. The findings suggest that sub-MICs of allicin are capable of affecting UPEC biofilm formation and dispersal, and decreasing UPEC adhesion ability and swimming motility. PMID- 27367678 TI - Use of Different Proteases to Obtain Flaxseed Protein Hydrolysates with Antioxidant Activity. AB - The antioxidant activity of flaxseed protein hydrolysates obtained using five different enzymes was evaluated. Proteins were isolated from flaxseed cake and were separately treated with papain, trypsin, pancreatin, Alcalase and Flavourzyme. The degree of hydrolysis (DH) was determined as the percentage of cleaved peptide bonds using a spectrophotometric method with o-phthaldialdehyde. The distribution of the molecular weights (MW) of the hydrolysis products was profiled using Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Tricine-SDS-PAGE) and size exclusion-high performance liquid chromatography (SE HPLC) separations. The antioxidant activities of the protein isolate and hydrolysates were probed for their radical scavenging activity using 2,2'-azino bis-(3-ethylbenzothiazoline-6-sulfonate) radical cation (ABTS(*+)) and photochemiluminescence (PCL-ACL) assays, and for their ferric reducing antioxidant power (FRAP) and ability to bind Fe(2+). The hydrolysates were more effective as antioxidants than the protein isolate in all systems. The PCL-ACL values of the hydrolysates ranged from 7.2 to 35.7 MUmol Trolox/g. Both the FRAP and ABTS(*+) scavenging activity differed among the hydrolysates to a lower extent, with the ranges of 0.20-0.24 mmol Fe(2+)/g and 0.17-0.22 mmol Trolox/g, respectively. The highest chelating activity (71.5%) was noted for the pancreatin hydrolysate. In general, the hydrolysates obtained using Alcalase and pancreatin had the highest antioxidant activity, even though their DH (15.4% and 29.3%, respectively) and the MW profiles of the peptides varied substantially. The O2(* ) scavenging activity and the ability to chelate Fe(2+) of the Flavourzyme hydrolysate were lower than those of the Alcalase and pancreatin hydrolysates. Papain was the least effective in releasing the peptides with antioxidant activity. The study showed that the type of enzyme used for flaxseed protein hydrolysis determines the antioxidant activity of the hydrolysates. PMID- 27367679 TI - Fernblock (Polypodium leucotomos Extract): Molecular Mechanisms and Pleiotropic Effects in Light-Related Skin Conditions, Photoaging and Skin Cancers, a Review. AB - Healthier life styles include increased outdoors time practicing sports and walking. This means increased exposure to the sun, leading to higher risk of sunburn, photoaging and skin cancer. In addition to topical barrier products, oral supplementations of various botanicals endowed with antioxidant activity are emerging as novel method of photoprotection. Polypodium leucotomos extract (PL, commercial name Fernblock((r)), IFC Group, Spain) is a powerful antioxidant due to its high content of phenolic compounds. PL is administered orally, with proven safety, and it can also be used topically. Its mechanisms include inhibition of the generation and release of reactive oxygen species (ROS) by ultraviolet (UV) light. It also prevents UV- and ROS-induced DNA damage with inhibition of AP1 and NF-kappaB and protection of natural antioxidant enzyme systems. At the cellular level, PL decreases cellular apoptosis and necrosis mediated UV and inhibits abnormal extracellular matrix remodeling. PL reduces inflammation, prevents immunosuppression, activates tumor suppressor p53 and inhibits UV-induced cyclooxygenase-2 (COX-2) enzyme expression. In agreement with increased p53 activity, PL decreased UV radiation-induced cell proliferation. PL also prevents common deletions mitochondrial DNA damage induced by UVA, and MMP-1 expression induced Visible Light and Infrared Radiation. These cellular and molecular effects are reflected in inhibitions of carcinogenesis and photoaging. PMID- 27367680 TI - The Immunogenicity of Colorectal Cancer in Relation to Tumor Development and Treatment. AB - Although most cancer types have been viewed as immunologically silent until recently, it has become increasingly clear that the immune system plays key roles in the course of tumor development. Remarkable progress towards understanding cancer immunogenicity and tumor-immune system interactions has revealed important implications for the design of novel immune-based therapies. Natural immune responses, but also therapeutic interventions, can modulate the tumor phenotype due to selective outgrowth of resistant subtypes. This is the result of heterogeneity of tumors, with genetic instability as a driving force, and obviously changes the immunogenicity of tumors. In this review, we discuss the immunogenicity of colorectal cancer (CRC) in relation to tumor development and treatment. As most tumors, CRC activates the immune system in various ways, and is also capable of escaping recognition and elimination by the immune system. Tumor-immune system interactions underlie the balance between immune control and immune escape, and may differ in primary tumors, in the circulation, and in liver metastases of CRC. Since CRC immunogenicity varies between tumors and individuals, novel immune-based therapeutic strategies should not only anticipate the molecular profile, but also the immunological profile of a specific tumor. PMID- 27367681 TI - TSPO PIGA Ligands Promote Neurosteroidogenesis and Human Astrocyte Well-Being. AB - The steroidogenic 18 kDa translocator protein (TSPO) is an emerging, attractive therapeutic tool for several pathological conditions of the nervous system. Here, 13 high affinity TSPO ligands belonging to our previously described N,N-dialkyl-2 phenylindol-3-ylglyoxylamide (PIGA) class were evaluated for their potential ability to affect the cellular Oxidative Metabolism Activity/Proliferation index, which is used as a measure of astrocyte well-being. The most active PIGA ligands were also assessed for steroidogenic activity in terms of pregnenolone production, and the values were related to the metabolic index in rat and human models. The results showed a positive correlation between the increase in the Oxidative Metabolism Activity/Proliferation index and the pharmacologically induced stimulation of steroidogenesis. The specific involvement of steroid molecules in mediating the metabolic effects of the PIGA ligands was demonstrated using aminoglutethimide, a specific inhibitor of the first step of steroid biosynthesis. The most promising steroidogenic PIGA ligands were the 2-naphthyl derivatives that showed a long residence time to the target, in agreement with our previous data. In conclusion, TSPO ligand-induced neurosteroidogenesis was involved in astrocyte well-being. PMID- 27367683 TI - Effect of Antimicrobial Denture Base Resin on Multi-Species Biofilm Formation. AB - Our aims of the research were to study the antimicrobial effect of dimethylaminododecyl methacrylate (DMADDM) modified denture base resin on multi species biofilms and the biocompatibility of this modified dental material. Candida albicans (C. albicans), Streptococcus mutans (S. mutans), Streptococcus sanguinis (S. sanguinis), as well as Actinomyces naeslundii (A. naeslundii) were used for biofilm formation on denture base resin. Colony forming unit (CFU) counts, microbial viability staining, and 2,3-bis(2-methoxy-4-nitro-5 sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) array were used to evaluate the antimicrobial effect of DMADDM. C. albicans staining and Real-time PCR were used to analyze the morphology and expression of virulence genes of C. albicans in biofilm. Lactate dehydrogenase (LDH) array and Real-time PCR were conducted to examine the results after biofilm co-cultured with epithelial cell. Hematoxylin and eosin (HE) staining followed by histological evaluation were used to study the biocompatibility of this modified material. We found that DMADDM containing groups reduced both biomass and metabolic activity of the biofilm significantly. DMADDM can also inhibit the virulence of C. albicans by means of inhibiting the hyphal development and downregulation of two virulence related genes. DMADDM significantly reduced the cell damage caused by multi-species biofilm according to the LDH activity and reduced the expression of IL-18 gene of the cells simultaneously. The in vivo histological evaluation proved that the addition of DMADDM less than 6.6% in denture material did not increase the inflammatory response (p > 0.05). Therefore, we proposed that the novel denture base resin containing DMADDM may be considered as a new promising therapeutic system against problems caused by microbes on denture base such as denture stomatitis. PMID- 27367682 TI - Aquaporins and Brain Tumors. AB - Brain primary tumors are among the most diverse and complex human cancers, and they are normally classified on the basis of the cell-type and/or the grade of malignancy (the most malignant being glioblastoma multiforme (GBM), grade IV). Glioma cells are able to migrate throughout the brain and to stimulate angiogenesis, by inducing brain capillary endothelial cell proliferation. This in turn causes loss of tight junctions and fragility of the blood-brain barrier, which becomes leaky. As a consequence, the most serious clinical complication of glioblastoma is the vasogenic brain edema. Both glioma cell migration and edema have been correlated with modification of the expression/localization of different isoforms of aquaporins (AQPs), a family of water channels, some of which are also involved in the transport of other small molecules, such as glycerol and urea. In this review, we discuss relationships among expression/localization of AQPs and brain tumors/edema, also focusing on the possible role of these molecules as both diagnostic biomarkers of cancer progression, and therapeutic targets. Finally, we will discuss the possibility that AQPs, together with other cancer promoting factors, can be exchanged among brain cells via extracellular vesicles (EVs). PMID- 27367684 TI - A WDR Gene Is a Conserved Member of a Chitin Synthase Gene Cluster and Influences the Cell Wall in Aspergillus nidulans. AB - WD40 repeat (WDR) proteins are pleiotropic molecular hubs. We identify a WDR gene that is a conserved genomic neighbor of a chitin synthase gene in Ascomycetes. The WDR gene is unique to fungi and plants, and was called Fungal Plant WD (FPWD). FPWD is within a cell wall metabolism gene cluster in the Ascomycetes (Pezizomycotina) comprising chsD, a Chs activator and a GH17 glucanase. The FPWD, AN1556.2 locus was deleted in Aspergillus nidulans strain SAA.111 by gene replacement and only heterokaryon transformants were obtained. The re-annotation of Aspergilli genomes shows that AN1556.2 consists of two tightly linked separate genes, i.e., the WDR gene and a putative beta-flanking gene of unknown function. The WDR and the beta-flanking genes are conserved genomic neighbors localized within a recently identified metabolic cell wall gene cluster in genomes of Aspergilli. The heterokaryons displayed increased susceptibility to drugs affecting the cell wall, and their phenotypes, observed by optical, confocal, scanning electron and atomic force microscopy, suggest cell wall alterations. Quantitative real-time PCR shows altered expression of some cell wall-related genes. The possible implications on cell wall biosynthesis are discussed. PMID- 27367686 TI - Planar Laser-Based QEPAS Trace Gas Sensor. AB - A novel quartz enhanced photoacoustic spectroscopy (QEPAS) trace gas detection scheme is reported in this paper. A cylindrical lens was employed for near infrared laser focusing. The laser beam was shaped as a planar line laser between the gap of the quartz tuning fork (QTF) prongs. Compared with a spherical lens based QEPAS sensor, the cylindrical lens-based QEPAS sensor has the advantages of easier laser beam alignment and a reduction of stringent stability requirements. Therefore, the reported approach is useful in long-term and continuous sensor operation. PMID- 27367685 TI - A Three-Dimensional Shape-Based Force and Stiffness-Sensing Platform for Tendon Driven Catheters. AB - This paper presents an efficient shape-based three-axial force and stiffness estimator for active catheters commonly implemented in cardiac ablation. The force-sensing capability provides important feedback for catheterization procedures including real-time control and catheter steering in autonomous navigation systems. The proposed platform is based on the introduced accurate and computationally efficient Cosserat rod model for tendon-driven catheters. The proposed nonlinear Kalman filter formulation for contact force estimation along with the developed catheter model provides a real-time force observer robust to nonlinearities and noise covariance uncertainties. Furthermore, the proposed platform enables stiffness estimation in addition to tip contact force sensing in different operational circumstances. The approach incorporates pose measurements which can be achieved using currently developed pose-sensing systems or imaging techniques. The method makes the approach compatible with the range of forces applied in clinical applications. The simulation and experimental results verify the viability of the introduced force and stiffness-sensing technique. PMID- 27367688 TI - High-Precision Hysteresis Sensing of the Quartz Crystal Inductance-to-Frequency Converter. AB - A new method for the automated measurement of the hysteresis of the temperature compensated inductance-to-frequency converter with a single quartz crystal is proposed. The new idea behind this method is a converter with two programmable analog switches enabling the automated measurement of the converter hysteresis, as well as the temperature compensation of the quartz crystal and any other circuit element. Also used is the programmable timing control device that allows the selection of different oscillating frequencies. In the proposed programmable method two different inductances connected in series to the quartz crystal are switched in a short time sequence, compensating the crystal's natural temperature characteristics (in the temperature range between 0 and 50 degrees C). The procedure allows for the measurement of the converter hysteresis at various values of capacitance connected in parallel with the quartz crystal for the converter sensitivity setting at selected inductance. It, furthermore, enables the measurement of hysteresis at various values of inductance at selected parallel capacitance (sensitivity) connected to the quartz crystal. The article shows that the proposed hysteresis measurement of the converter, which converts the inductance in the range between 95 and 100 MUH to a frequency in the range between 1 and 200 kHz, has only 7 * 10(-13) frequency instability (during the temperature change between 0 and 50 degrees C) with a maximum 1 * 10(-11) hysteresis frequency difference. PMID- 27367687 TI - Microsoft Kinect Visual and Depth Sensors for Breathing and Heart Rate Analysis. AB - This paper is devoted to a new method of using Microsoft (MS) Kinect sensors for non-contact monitoring of breathing and heart rate estimation to detect possible medical and neurological disorders. Video sequences of facial features and thorax movements are recorded by MS Kinect image, depth and infrared sensors to enable their time analysis in selected regions of interest. The proposed methodology includes the use of computational methods and functional transforms for data selection, as well as their denoising, spectral analysis and visualization, in order to determine specific biomedical features. The results that were obtained verify the correspondence between the evaluation of the breathing frequency that was obtained from the image and infrared data of the mouth area and from the thorax movement that was recorded by the depth sensor. Spectral analysis of the time evolution of the mouth area video frames was also used for heart rate estimation. Results estimated from the image and infrared data of the mouth area were compared with those obtained by contact measurements by Garmin sensors (www.garmin.com). The study proves that simple image and depth sensors can be used to efficiently record biomedical multidimensional data with sufficient accuracy to detect selected biomedical features using specific methods of computational intelligence. The achieved accuracy for non-contact detection of breathing rate was 0.26% and the accuracy of heart rate estimation was 1.47% for the infrared sensor. The following results show how video frames with depth data can be used to differentiate different kinds of breathing. The proposed method enables us to obtain and analyse data for diagnostic purposes in the home environment or during physical activities, enabling efficient human-machine interaction. PMID- 27367689 TI - An Efficient Interactive Model for On-Demand Sensing-As-A-Servicesof Sensor Cloud. AB - This paper proposes an efficient interactive model for the sensor-cloud to enable the sensor-cloud to efficiently provide on-demand sensing services for multiple applications with different requirements at the same time. The interactive model is designed for both the cloud and sensor nodes to optimize the resource consumption of physical sensors, as well as the bandwidth consumption of sensing traffic. In the model, the sensor-cloud plays a key role in aggregating application requests to minimize the workloads required for constrained physical nodes while guaranteeing that the requirements of all applications are satisfied. Physical sensor nodes perform their sensing under the guidance of the sensor cloud. Based on the interactions with the sensor-cloud, physical sensor nodes adapt their scheduling accordingly to minimize their energy consumption. Comprehensive experimental results show that our proposed system achieves a significant improvement in terms of the energy consumption of physical sensors, the bandwidth consumption from the sink node to the sensor-cloud, the packet delivery latency, reliability and scalability, compared to current approaches. Based on the obtained results, we discuss the economical benefits and how the proposed system enables a win-win model in the sensor-cloud. PMID- 27367690 TI - Spectral Characterization of a Prototype SFA Camera for Joint Visible and NIR Acquisition. AB - Multispectral acquisition improves machine vision since it permits capturing more information on object surface properties than color imaging. The concept of spectral filter arrays has been developed recently and allows multispectral single shot acquisition with a compact camera design. Due to filter manufacturing difficulties, there was, up to recently, no system available for a large span of spectrum, i.e., visible and Near Infra-Red acquisition. This article presents the achievement of a prototype of camera that captures seven visible and one near infra-red bands on the same sensor chip. A calibration is proposed to characterize the sensor, and images are captured. Data are provided as supplementary material for further analysis and simulations. This opens a new range of applications in security, robotics, automotive and medical fields. PMID- 27367691 TI - Strategic Decision-Making Learning from Label Distributions: An Approach for Facial Age Estimation. AB - Nowadays, label distribution learning is among the state-of-the-art methodologies in facial age estimation. It takes the age of each facial image instance as a label distribution with a series of age labels rather than the single chronological age label that is commonly used. However, this methodology is deficient in its simple decision-making criterion: the final predicted age is only selected at the one with maximum description degree. In many cases, different age labels may have very similar description degrees. Consequently, blindly deciding the estimated age by virtue of the highest description degree would miss or neglect other valuable age labels that may contribute a lot to the final predicted age. In this paper, we propose a strategic decision-making label distribution learning algorithm (SDM-LDL) with a series of strategies specialized for different types of age label distribution. Experimental results from the most popular aging face database, FG-NET, show the superiority and validity of all the proposed strategic decision-making learning algorithms over the existing label distribution learning and other single-label learning algorithms for facial age estimation. The inner properties of SDM-LDL are further explored with more advantages. PMID- 27367692 TI - Silica-gel Particles Loaded with an Ionic Liquid for Separation of Zr(IV) Prior to Its Determination by ICP-OES. AB - A new ionic liquid loaded silica gel amine (SG-APTMS-N,N-EPANTf2) was developed, as an adsorptive material, for selective adsorption and determination of zirconium, Zr(IV), without the need for a chelating intermediate. Based on a selectivity study, the SG-APTMS-N,N-EPANTf2 phase showed a perfect selectivity towards Zr(IV) at pH 4 as compared to other metallic ions, including gold [Au(III)], copper [Cu(II)], cobalt [Co(II)], chromium [Cr(III)], lead [Pb(II)], selenium [Se(IV)] and mercury [Hg(II)] ions. The influence of pH, Zr(IV) concentration, contact time and interfering ions on SG-APTMS-N,N-EPANTf2 uptake for Zr(IV) was evaluated. The presence of incorporated donor atoms in newly synthesized SG-APTMS-N,N-EPANTf2 phase played a significant role in enhancing its uptake capacity of Zr(IV) by 78.64% in contrast to silica gel (activated). The equilibrium and kinetic information of Zr(IV) adsorption onto SG-APTMS-N,N EPANTf2 were best expressed by Langmuir and pseudo second-order kinetic models, respectively. General co-existing cations did not interfere with the extraction and detection of Zr(IV). Finally, the analytical efficiency of the newly developed method was also confirmed by implementing it for the determination of Zr(IV) in several water samples. PMID- 27367693 TI - Amperometric Non-Enzymatic Hydrogen Peroxide Sensor Based on Aligned Zinc Oxide Nanorods. AB - Zinc oxide (ZnO) nanorods (NRs) have been synthesized via the hydrothermal process. The NRs were grown over a conductive glass substrate. A non-enzymatic electrochemical sensor for hydrogen peroxide (H2O2), based on the prepared ZnO NRs, was examined through the use of current-voltage measurements. The measured currents, as a function of H2O2 concentrations ranging from 10 MUM to 700 MUM, revealed two distinct behaviours and good performance, with a lower detection limit (LOD) of 42 MUM for the low range of H2O2 concentrations (first region), and a LOD of 143.5 MUM for the higher range of H2O2 concentrations (second region). The prepared ZnO NRs show excellent electrocatalytic activity. This enables a measurable and stable output current. The results were correlated with the oxidation process of the H2O2 and revealed a good performance for the ZnO NR non-enzymatic H2O2 sensor. PMID- 27367694 TI - Development of a Calibration Strip for Immunochromatographic Assay Detection Systems. AB - With many benefits and applications, immunochromatographic (ICG) assay detection systems have been reported on a great deal. However, the existing research mainly focuses on increasing the dynamic detection range or application fields. Calibration of the detection system, which has a great influence on the detection accuracy, has not been addressed properly. In this context, this work develops a calibration strip for ICG assay photoelectric detection systems. An image of the test strip is captured by an image acquisition device, followed by performing a fuzzy c-means (FCM) clustering algorithm and maximin-distance algorithm for image segmentation. Additionally, experiments are conducted to find the best characteristic quantity. By analyzing the linear coefficient, an average value of hue (H) at 14 min is chosen as the characteristic quantity and the empirical formula between H and optical density (OD) value is established. Therefore, H, saturation (S), and value (V) are calculated by a number of selected OD values. Then, H, S, and V values are transferred to the RGB color space and a high resolution printer is used to print the strip images on cellulose nitrate membranes. Finally, verification of the printed calibration strips is conducted by analyzing the linear correlation between OD and the spectral reflectance, which shows a good linear correlation (R2 = 98.78%). PMID- 27367695 TI - A Proof-of-Concept for Semantically Interoperable Federation of IoT Experimentation Facilities. AB - The Internet-of-Things (IoT) is unanimously identified as one of the main pillars of future smart scenarios. The potential of IoT technologies and deployments has been already demonstrated in a number of different application areas, including transport, energy, safety and healthcare. However, despite the growing number of IoT deployments, the majority of IoT applications tend to be self-contained, thereby forming application silos. A lightweight data centric integration and combination of these silos presents several challenges that still need to be addressed. Indeed, the ability to combine and synthesize data streams and services from diverse IoT platforms and testbeds, holds the promise to increase the potentiality of smart applications in terms of size, scope and targeted business context. In this article, a proof-of-concept implementation that federates two different IoT experimentation facilities by means of semantic-based technologies will be described. The specification and design of the implemented system and information models will be described together with the practical details of the developments carried out and its integration with the existing IoT platforms supporting the aforementioned testbeds. Overall, the system described in this paper demonstrates that it is possible to open new horizons in the development of IoT applications and experiments at a global scale, that transcend the (silo) boundaries of individual deployments, based on the semantic interconnection and interoperability of diverse IoT platforms and testbeds. PMID- 27367696 TI - Robust Control for the Segway with Unknown Control Coefficient and Model Uncertainties. AB - The Segway, which is a popular vehicle nowadays, is an uncertain nonlinear system and has an unknown time-varying control coefficient. Thus, we should consider the unknown time-varying control coefficient and model uncertainties to design the controller. Motivated by this observation, we propose a robust control for the Segway with unknown control coefficient and model uncertainties. To deal with the time-varying unknown control coefficient, we employ the Nussbaum gain technique. We introduce an auxiliary variable to solve the underactuated problem. Due to the prescribed performance control technique, the proposed controller does not require the adaptive technique, neural network, and fuzzy logic to compensate the uncertainties. Therefore, it can be simple. From the Lyapunov stability theory, we prove that all signals in the closed-loop system are bounded. Finally, we provide the simulation results to demonstrate the effectiveness of the proposed control scheme. PMID- 27367697 TI - Photon-Counting Arrays for Time-Resolved Imaging. AB - The paper presents a camera comprising 512 * 128 pixels capable of single-photon detection and gating with a maximum frame rate of 156 kfps. The photon capture is performed through a gated single-photon avalanche diode that generates a digital pulse upon photon detection and through a digital one-bit counter. Gray levels are obtained through multiple counting and accumulation, while time-resolved imaging is achieved through a 4-ns gating window controlled with subnanosecond accuracy by a field-programmable gate array. The sensor, which is equipped with microlenses to enhance its effective fill factor, was electro-optically characterized in terms of sensitivity and uniformity. Several examples of capture of fast events are shown to demonstrate the suitability of the approach. PMID- 27367698 TI - Quantum Random Number Generation Using a Quanta Image Sensor. AB - A new quantum random number generation method is proposed. The method is based on the randomness of the photon emission process and the single photon counting capability of the Quanta Image Sensor (QIS). It has the potential to generate high-quality random numbers with remarkable data output rate. In this paper, the principle of photon statistics and theory of entropy are discussed. Sample data were collected with QIS jot device, and its randomness quality was analyzed. The randomness assessment method and results are discussed. PMID- 27367699 TI - A 75-ps Gated CMOS Image Sensor with Low Parasitic Light Sensitivity. AB - In this study, a 40 * 48 pixel global shutter complementary metal-oxide semiconductor (CMOS) image sensor with an adjustable shutter time as low as 75 ps was implemented using a 0.5-MUm mixed-signal CMOS process. The implementation consisted of a continuous contact ring around each p+/n-well photodiode in the pixel array in order to apply sufficient light shielding. The parasitic light sensitivity of the in-pixel storage node was measured to be 1/8.5 * 107 when illuminated by a 405-nm diode laser and 1/1.4 * 104 when illuminated by a 650-nm diode laser. The pixel pitch was 24 MUm, the size of the square p+/n-well photodiode in each pixel was 7 MUm per side, the measured random readout noise was 217 e(-) rms, and the measured dynamic range of the pixel of the designed chip was 5500:1. The type of gated CMOS image sensor (CIS) that is proposed here can be used in ultra-fast framing cameras to observe non-repeatable fast-evolving phenomena. PMID- 27367700 TI - Game Theory Meets Wireless Sensor Networks Security Requirements and Threats Mitigation: A Survey. AB - We present a study of using game theory for protecting wireless sensor networks (WSNs) from selfish behavior or malicious nodes. Due to scalability, low complexity and disseminated nature of WSNs, malicious attacks can be modeled effectively using game theory. In this study, we survey the different game theoretic defense strategies for WSNs. We present a taxonomy of the game theory approaches based on the nature of the attack, whether it is caused by an external attacker or it is the result of an internal node acting selfishly or maliciously. We also present a general trust model using game theory for decision making. We, finally, identify the significant role of evolutionary games for WSNs security against intelligent attacks; then, we list several prospect applications of game theory to enhance the data trustworthiness and node cooperation in different WSNs. PMID- 27367701 TI - An Enhanced Technique for Ultrasonic Flow Metering Featuring Very Low Jitter and Offset. AB - This paper proposes a new, improved method for water flow metering. It applies to a transit time ultrasonic flow meter device. In principle, the flow of a given liquid in a pipe is obtained by measuring the transit times of an ultrasonic wave in the upstream and downstream directions. The difference between these times is, in theory, linearly proportional to the liquid flow velocity. However, the fainter the flow is, the smaller the transit time difference (TTD) is. This difference can be as low as a few picoseconds, which gives rise to many technical difficulties in measuring such a small time difference with a given accuracy. The proposed method relies on measuring the TTD indirectly by computing the phase difference between the steady-state parts of the received signals in the upstream and downstream directions and by using a least-square-sine-fitting technique. This reduces the effect of the jitter noise and the offset, which limit measurement precision at very low flow velocity. The obtained measurement results illustrate the robustness of the proposed method, as we measure the TTD at no flow conditions, with a precision as low as 10 ps peak-to-peak and a TTD offset of zero, within a temperature range from room temperature to 80 degrees C. This allows us to reach a smaller minimum detectable flow when compared with previous techniques. The proposed method exhibits a better trade-off between measurement accuracy and system complexity. It can be completely integrated in an ASIC (application specific integrated circuit) or incorporated in a CPU- or micro controller-based system. PMID- 27367702 TI - Microcantilever Displacement Measurement Using a Mechanically Modulated Optical Feedback Interferometer. AB - Microcantilever motion detection is a useful tool for the characterization of the physical, chemical and biological properties of materials. In the past, different approaches have been proposed and tested to enhance the behavior, size and simplicity of microcantilever motion detectors. In this paper, a new approach to measure microcantilever motion with nanometric resolution is presented. The proposed approach is based on the concept of mechanically-modulated optical feedback interferometry, a technique that has shown displacement measurement capabilities well within the nanometric scale and that, due to its size, compactness and low cost, may be a suitable choice for measuring nanometric motions in cantilever-like sensors. It will be shown that the sensor, in its current state of development, is capable of following a cantilever sinusoidal trajectory at different sets of frequencies ranging up to 200 Hz and peak to peak amplitudes up to lambda / 2 with experimental resolutions in the lambda / 100 range. PMID- 27367703 TI - Quality-Related Monitoring and Grading of Granulated Products by Weibull Distribution Modeling of Visual Images with Semi-Supervised Learning. AB - The topic of online product quality inspection (OPQI) with smart visual sensors is attracting increasing interest in both the academic and industrial communities on account of the natural connection between the visual appearance of products with their underlying qualities. Visual images captured from granulated products (GPs), e.g., cereal products, fabric textiles, are comprised of a large number of independent particles or stochastically stacking locally homogeneous fragments, whose analysis and understanding remains challenging. A method of image statistical modeling-based OPQI for GP quality grading and monitoring by a Weibull distribution(WD) model with a semi-supervised learning classifier is presented. WD-model parameters (WD-MPs) of GP images' spatial structures, obtained with omnidirectional Gaussian derivative filtering (OGDF), which were demonstrated theoretically to obey a specific WD model of integral form, were extracted as the visual features. Then, a co-training-style semi-supervised classifier algorithm, named COSC-Boosting, was exploited for semi-supervised GP quality grading, by integrating two independent classifiers with complementary nature in the face of scarce labeled samples. Effectiveness of the proposed OPQI method was verified and compared in the field of automated rice quality grading with commonly-used methods and showed superior performance, which lays a foundation for the quality control of GP on assembly lines. PMID- 27367704 TI - Strategies to Overcome Heparins' Low Oral Bioavailability. AB - Even after a century, heparin is still the most effective anticoagulant available with few side effects. The poor oral absorption of heparins triggered the search for strategies to achieve oral bioavailability since this route has evident advantages over parenteral administration. Several approaches emerged, such as conjugation of heparins with bile acids and lipids, formulation with penetration enhancers, and encapsulation of heparins in micro and nanoparticles. Some of these strategies appear to have potential as good delivery systems to overcome heparin's low oral bioavailability. Nevertheless, none have reached the market yet. Overall, this review aims to provide insights regarding the oral bioavailability of heparin. PMID- 27367705 TI - Structural Features and Potent Antidepressant Effects of Total Sterols and beta sitosterol Extracted from Sargassum horneri. AB - The purified total sterols and beta-sitosterol extracted from Sargassum horneri were evaluated for their antidepressant-like activity using the forced swim test (FST) and tail suspension test (TST) in mice. Total sterols and beta-sitosterol significantly reduced the immobility time in the FST and TST. Total sterols were administered orally for 7 days at doses of 50, 100, and 200 mg/kg, and beta sitosterol was administered intraperitoneally at doses of 10, 20, and 30 mg/kg. beta-sitosterol had no effect on locomotor activity in the open field test. In addition, total sterols and beta-sitosterol significantly increased NE, 5-HT, and the metabolite 5-HIAA in the mouse brain, suggesting that the antidepressant-like activity may be mediated through these neurotransmitters. PMID- 27367706 TI - Falls from Height in the Construction Industry: A Critical Review of the Scientific Literature. AB - Globally, falls from height (FFH) are a substantial public health jeopardy and are among the important leading causes of serious and fatal injuries for construction workers. A comprehensive understanding of the causal factors in FFH incidents is urgently required; however, the literature appears to lack a scientific review of FFH. In this study, 297 articles that contribute to the topic of fall incidents were reviewed. Seventy-five (75) articles met the criteria for relevance and were aggregated in a database to support a critical review. A synthesis of macro-variables approach was adopted rather than a structured meta-analysis. Such a method of analysis provides the flexibility to combine previous studies' findings. The most common factors associated with FFH are risky activities, individual characteristics, site conditions, organizational characteristics, agents (scaffolds/ladders) and weather conditions. The outcomes contributed to identifying the most significant research area for safety enhancement by improving engineering facilities, behaviour investigations and FFH prevention methods. PMID- 27367708 TI - Spectral Estimation Model Construction of Heavy Metals in Mining Reclamation Areas. AB - The study reported here examined, as the research subject, surface soils in the Liuxin mining area of Xuzhou, and explored the heavy metal content and spectral data by establishing quantitative models with Multivariable Linear Regression (MLR), Generalized Regression Neural Network (GRNN) and Sequential Minimal Optimization for Support Vector Machine (SMO-SVM) methods. The study results are as follows: (1) the estimations of the spectral inversion models established based on MLR, GRNN and SMO-SVM are satisfactory, and the MLR model provides the worst estimation, with R2 of more than 0.46. This result suggests that the stress sensitive bands of heavy metal pollution contain enough effective spectral information; (2) the GRNN model can simulate the data from small samples more effectively than the MLR model, and the R2 between the contents of the five heavy metals estimated by the GRNN model and the measured values are approximately 0.7; (3) the stability and accuracy of the spectral estimation using the SMO-SVM model are obviously better than that of the GRNN and MLR models. Among all five types of heavy metals, the estimation for cadmium (Cd) is the best when using the SMO SVM model, and its R2 value reaches 0.8628; (4) using the optimal model to invert the Cd content in wheat that are planted on mine reclamation soil, the R2 and RMSE between the measured and the estimated values are 0.6683 and 0.0489, respectively. This result suggests that the method using the SMO-SVM model to estimate the contents of heavy metals in wheat samples is feasible. PMID- 27367707 TI - Short-Term Exposure to Air Pollution and Cardiac Arrhythmia: A Meta-Analysis and Systematic Review. AB - The objective was to assess the transient association between air pollution and cardiac arrhythmia. Five databases were searched for studies investigating the association between daily increases in air pollutants (PM2.5, PM10, carbon monoxide, nitrogen dioxide, sulfur dioxide and ozone) and arrhythmia hospitalization or arrhythmia mortality. Two reviewers independently selected studies, extracted data, and assessed risk of bias. Outcomes were analyzed via a random-effects model and reported as relative risk and 95% confidence interval. 25 studies satisfied our inclusion criteria and 23 contributed to the meta analysis. Arrhythmia hospitalization or mortality were associated with increases in PM2.5 (RR = 1.015 per 10 MUg/m3, 95% CI: 1.006-1.024), PM10 (RR = 1.009 per 10 MUg/m3, 95% CI: 1.004-1.014), carbon monoxide (RR = 1.041 per 1 ppm, 95% CI: 1.017-1.065), nitrogen dioxide (RR = 1.036 per 10 ppb, 95% CI: 1.020-1.053), and sulfur dioxide (RR = 1.021 per 10 ppb, 95% CI: 1.003-1.039), but not ozone (RR = 1.012 per 10 ppb, 95% CI: 0.997-1.027). Both particulate and gaseous components, with the exception of ozone, have a temporal association with arrhythmia hospitalization or mortality. Compared with Europe and North America, a stronger association was noted in Asia. PMID- 27367709 TI - Public Parks in Hong Kong: Characteristics of Physical Activity Areas and Their Users. AB - Public parks, salient locations for engaging populations in health promoting physical activity, are especially important in high-density cities. We used the System for Observing Physical Activity in Communities (SOPARC) to conduct the first-ever surveillance study of nine public parks in Hong Kong (288 observation sessions during 36 weekdays and 36 weekend days) and observed 28,585 visitors in 262 diverse areas/facilities. Parks were widely used throughout the day on weekdays and weekend days and across summer and autumn; visitor rates were among the highest seen in 24 SOPARC studies. In contrast to other studies where teens and children dominated park use, most visitors (71%) were adults and seniors. More males (61%) than females used the parks, and they dominated areas designed for sports. Over 60% of visitors were observed engaging in moderate-to-vigorous physical activity, a rate higher than other SOPARC studies. Facilities with user fees were less accessible than non-fee areas, but they provided relatively more supervised and organized activities. Assessing parks by age, gender, and physical activity can provide useful information relative to population health. This study not only provides information useful to local administrators for planning and programming park facilities relative to physical activity, but it also provides a baseline for comparison by other high-density cities. PMID- 27367710 TI - Monitoring of Waterborne Parasites in Two Drinking Water Treatment Plants: A Study in Sarawak, Malaysia. AB - The occurrence of waterborne parasites coupled with water parameters at various processing sites of two drinking water treatment plants (A and B) and seven distribution system (DS) sites in Sarawak, Malaysia were studied. Ten liters of water underwent immunomagnetic separation (IMS) technique to detect the presence of Giardia and Cryptosporidium (oo)cysts. The remaining supernatant was used to detect other parasites whilst 50 mL of water sample was each used in the detection of free-living amoebae and fecal coliforms. Sampled water was positive for Giardia (32.9%; 28/85), Cryptosporidium (18.8%; 16/85) followed by Spirometra ova-like (25.9%; 22/85), Blastocystis-like (25.9%; 22/85), nematode larvae-like (8.2%; 7/85) and Taenia ova-like (1.2%; 1/85). Meanwhile, 90.2% (55/61) samples were positive for Acanthamoeba and Naegleria via cultivation and of these, 11 isolates were confirmed as Acanthamoeba genotype T3 (5/7) and T4 (2/7) followed by Naegleria sp. (4/11), Naegleria italica (2/11), Naegleria australiensis (1/11), Naegleria angularis (1/11) and Vahlkampfia sp. (3/11). Cryptosporidium, Acanthamoeba and Naegleria were also detected in one of the seven tested DS sites. Only Giardia and Cryptosporidium showed significant correlations with fluoride and fecal coliforms. These results describe the occurrence of waterborne parasites that will assist key stakeholders in mitigating contamination at the specific sites. PMID- 27367711 TI - Lysyl Oxidase Gene G473A Polymorphism and Cigarette Smoking in Association with a High Risk of Lung and Colorectal Cancers in a North Chinese Population. AB - The relationship among the lysyl oxidase (LOX) G473A single nucleotide polymorphism (SNP), cigarette smoking and lung, colorectal, colon and rectum cancer susceptibility was studied in 200 cases of lung cancer, 335 cases of colorectal cancer including 130 cases of colon cancer and 205 cases of rectum cancer, and 335 healthy people in Tangshan, China. Peripheral blood DNA samples were collected, DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) performed, followed by multivariate logistic regression analysis. In comparison to LOX473GG genotype carriers, individuals with LOX473AA exhibited a higher susceptibility to lung, colon-rectum, colon, and rectum cancers with OR values amounting to 3.84-, 2.74-, 2.75-, and 2.74-fold of the control, respectively. In the LOX 473AA-positive population, females were more susceptible than males to carcinogenesis with OR values (female vs. male): 5.25 vs. 3.23, 2.29 vs. 1.51, 2.27 vs. 1.45, and 2.25 vs. 1.53, respectively, for lung, colon-rectum combined, colon, and rectum cancers. LOX G473A polymorphism apparently elevated human sensitivity to cigarette smoking carcinogens for eliciting cancers in the lung and colon only. Thus, LOX G473A polymorphism positively correlates with carcinogenesis and it may be used as an ideal intrinsic biomarker for prediction or diagnosis of carcinogenesis in humans. PMID- 27367712 TI - Household Air Pollution Exposure and Influence of Lifestyle on Respiratory Health and Lung Function in Belizean Adults and Children: A Field Study. AB - Household air pollution (HAP) contributes to the global burden of disease. Our primary purpose was to determine whether HAP exposure was associated with reduced lung function and respiratory and non-respiratory symptoms in Belizean adults and children. Our secondary purpose was to investigate whether lifestyle (physical activity (PA) and fruit and vegetable consumption (FV)) is associated with reported symptoms. Belizean adults (n = 67, 19 Male) and children (n = 23, 6 Male) from San Ignacio Belize and surrounding areas participated in this cross sectional study. Data collection took place at free walk-in clinics. Investigators performed initial screenings and administered questionnaires on (1) sources of HAP exposure; (2) reported respiratory and non-respiratory symptoms and (3) validated lifestyle questionnaires. Participants then performed pulmonary function tests (PFTs) and exhaled breath carbon monoxide (CO). There were no significant associations between HAP exposure and pulmonary function in adults. Increased exhaled CO was associated with a significantly lower forced expiratory volume in 1-s divided by forced vital capacity (FEV1/FVC) in children. Exposed adults experienced headaches, burning eyes, wheezing and phlegm production more frequently than unexposed adults. Adults who met PA guidelines were less likely to experience tightness and pressure in the chest compared to those not meeting guidelines. In conclusion, adults exposed to HAP experienced greater respiratory and non-respiratory symptoms, which may be attenuated by lifestyle modifications. PMID- 27367713 TI - What Attracts People to Visit Community Open Spaces? A Case Study of the Overseas Chinese Town Community in Shenzhen, China. AB - A well-designed open space that encourages outdoor activity and social communication is a community asset that could potentially contribute to the health of local residents and social harmony of the community. Numerous factors may influence the use of each single space and may result in a variety of visitors. Compared with previous studies that focused on accessibility, this study highlights the relationship between the utilization and characteristics of community open spaces in China. The Overseas Chinese Town community in Shenzhen is regarded as an example. The association between the number of visitors and space characteristics is examined with multivariate regression models. Results show that large areas with accessible lawns, well-maintained footpaths, seats, commercial facilities, and water landscapes are important characteristics that could increase the use of community open spaces. However, adding green vegetation, sculptures, and landscape accessories in open spaces has limited effects on increasing the outdoor activities of residents. Thus, to increase the use of community open spaces, landscape designers should focus more on creating user-oriented spaces with facilities that encourage active use than on improving ornamental vegetation and accessories. PMID- 27367714 TI - Environmental Light and Its Relationship with Electromagnetic Resonances of Biomolecular Interactions, as Predicted by the Resonant Recognition Model. AB - The meaning and influence of light to biomolecular interactions, and consequently to health, has been analyzed using the Resonant Recognition Model (RRM). The RRM proposes that biological processes/interactions are based on electromagnetic resonances between interacting biomolecules at specific electromagnetic frequencies within the infra-red, visible and ultra-violet frequency ranges, where each interaction can be identified by the certain frequency critical for resonant activation of specific biological activities of proteins and DNA. We found that: (1) the various biological interactions could be grouped according to their resonant frequency into super families of these functions, enabling simpler analyses of these interactions and consequently analyses of influence of electromagnetic frequencies to health; (2) the RRM spectrum of all analyzed biological functions/interactions is the same as the spectrum of the sun light on the Earth, which is in accordance with fact that life is sustained by the sun light; (3) the water is transparent to RRM frequencies, enabling proteins and DNA to interact without loss of energy; (4) the spectrum of some artificial sources of light, as opposed to the sun light, do not cover the whole RRM spectrum, causing concerns for disturbance to some biological functions and consequently we speculate that it can influence health. PMID- 27367715 TI - A Cross-Sectional Study of Heat Wave-Related Knowledge, Attitude, and Practice among the Public in the Licheng District of Jinan City, China. AB - Knowledge, attitude, and practice (KAP) are three key components for reducing the adverse health impacts of heat waves. However, research in eastern China regarding this is scarce. The present study aimed to evaluate the heat wave related KAP of a population in Licheng in northeast China. This cross-sectional study included 2241 participants. Data regarding demographic characteristics, KAP, and heat illnesses were collected using a structured questionnaire. Univariate analysis and unconditional logistic regression models were used to analyze the data. Most residents had high KAP scores, with a mean score of 12.23 (standard deviation = 2.23) on a 17-point scale. Urban women and participants aged 35-44 years had relatively high total scores, and those with high education levels had the highest total score. There was an increased risk of heat-related illness among those with knowledge scores of 3-5 on an 8-point scale with mean score of 5.40 (standard deviation = 1.45). Having a positive attitude toward sunstroke prevention and engaging in more preventive practices to avoid heat exposure had a protective interaction effect on reducing the prevalence of heat related illnesses. Although the KAP scores were relatively high, knowledge and practice were lacking to some extent. Therefore, governments should further develop risk-awareness strategies that increase awareness and knowledge regarding the adverse health impact of heat and help in planning response strategies to improve the ability of individuals to cope with heat waves. PMID- 27367716 TI - Development of Neutralization Assay Using an eGFP Chikungunya Virus. AB - Chikungunya virus (CHIKV), a member of the Alphavirus genus, is an important human emerging/re-emerging pathogen. Currently, there are no effective antiviral drugs or vaccines against CHIKV infection. Herein, we construct an infectious clone of CHIKV and an eGFP reporter CHIKV (eGFP-CHIKV) with an isolated strain (assigned to Asian lineage) from CHIKV-infected patients. The eGFP-CHIKV reporter virus allows for direct visualization of viral replication through the levels of eGFP expression. Using a known CHIKV inhibitor, ribavirin, we confirmed that the eGFP-CHIKV reporter virus could be used to identify inhibitors against CHIKV. Importantly, we developed a novel and reliable eGFP-CHIKV reporter virus-based neutralization assay that could be used for rapid screening neutralizing antibodies against CHIKV. PMID- 27367718 TI - The p22 RNA Silencing Suppressor of the Crinivirus Tomato chlorosis virus is Dispensable for Local Viral Replication but Important for Counteracting an Antiviral RDR6-Mediated Response during Systemic Infection. AB - Among the components of the RNA silencing pathway in plants, RNA-dependent RNA polymerases (RDRs) play fundamental roles in antiviral defence. Here, we demonstrate that the Nicotiana benthamiana RDR6 is involved in defence against the bipartite crinivirus (genus Crinivirus, family Closteroviridae) Tomato chlorosis virus (ToCV). Additionally, by producing a p22-deficient ToCV infectious mutant clone (ToCVDeltap22), we studied the role of this viral suppressor of RNA silencing in viral infection in both wild-type and RDR6 silenced N. benthamiana (NbRDR6i) plants. We demonstrate that p22 is dispensable for the replication of ToCV, where RDR6 appears not to have any effect. Furthermore, the finding that ToCV?p22 systemic accumulation was impaired in wild type N. benthamiana but not in NbRDR6i plants suggests a role for p22 in counteracting an RDR6-mediated antiviral response of the plant during systemic infection. PMID- 27367719 TI - Modeling the Effect of Replacing Sugar-Sweetened Beverage Consumption with Water on Energy Intake, HBI Score, and Obesity Prevalence. AB - Sugar-sweetened beverages (SSB) contribute to excessive weight gain through added energy intake. Replacing SSB with water is one strategy that has shown promise in helping lower excessive energy intake. Using nationally representative data from US adults (n = 19,718) from NHANES 2007-2012 we examine the impact of replacing SSB with water on Healthy Beverage Index (HBI) scores and obesity prevalence. Replacing an 8-ounce serving of SSB with water lowered the percent of energy from beverages from 17% to 11% (among those consuming 1 serving SSB/day). Reductions in the percent energy from beverages were observed across all SSB consumption groups (1-2 servings/day and >2 servings/day). Among adults there was a 9% to 21% improvement in HBI score when one serving of water replaced one serving of SSB. Using previously published randomized controlled trials (RCT) and meta-analyses of measured weight loss we also predicted a reduction in the prevalence of obesity (observed: 35.2%; predicted 33.5%-34.9%, p < 0.05) and increase in the prevalence of normal weight (observed: 29.7%; high weight loss: 31.3%, p < 0.05). Our findings provide further epidemiologic evidence that water in the place of SSB can be used as a strategy to limit energy intake and help individuals meet beverage intake recommendations. PMID- 27367720 TI - Thyroid Function among Breastfed Children with Chronically Excessive Iodine Intakes. AB - Iodine excess may impair thyroid function and trigger adverse health consequences for children. This study aims to describe iodine status among breastfed infants with high iodine exposure in the Saharawi refugee camps Algeria, and further assess thyroid function and iodine status among the children three years later. In 2010, a cross-sectional study among 111 breastfed children aged 0-6 months was performed (baseline study). In 2013, a second cross-sectional study (follow-up study) was conducted among 289 children; 213 newly selected and 76 children retrieved from baseline. Urinary iodine concentration (UIC) and breast milk iodine concentration (BMIC) were measured at baseline. UIC, thyroid hormones and serum thyroglobulin (Tg) were measured at follow-up. At baseline and follow-up, 88% and 72% had excessive iodine intakes (UIC >= 300 ug/L), respectively. At follow-up, 24% had a thyroid hormone disturbance and/or elevated serum Tg, including 9% with subclinical hypothyroidism (SCH), 4% with elevated fT3 and 14% with elevated Tg. Children with SCH had poorer linear growth and were more likely to be underweight than the children without SCH. Excessive iodine intakes and thyroid disturbances were common among children below four years of age in our study. Further, SCH seemed to be associated with poor growth and weight. PMID- 27367717 TI - Who Regulates Whom? An Overview of RNA Granules and Viral Infections. AB - After viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mRNA translation (protein synthesis) and the assembly of RNA granules. Two of these RNA granules have been well characterized in yeast and mammalian cells, stress granules (SGs), which are translationally silent sites of RNA triage and processing bodies (PBs), which are involved in mRNA degradation. This review discusses the role of these RNA granules in the evasion of anti-viral stress responses through virus-induced remodeling of cellular ribonucleoproteins (RNPs). PMID- 27367721 TI - Mangiferin and Cancer: Mechanisms of Action. AB - Mangiferin, a bioactive compound derived primarily from Anacardiaceae and Gentianaceae families and found in mangoes and honeybush tea, has been extensively studied for its therapeutic properties. Mangiferin has shown promising chemotherapeutic and chemopreventative potential. This review focuses on the effect of mangiferin on: (1) inflammation, with respect to NFkappaB, PPAR? and the immune system; (2) cell cycle, the MAPK pathway G2/M checkpoint; (3) proliferation and metastasis, and implications on beta-catenin, MMPs, EMT, angiogenesis and tumour volume; (4) apoptosis, with a focus on Bax/Bcl ratios, intrinsic/extrinsic apoptotic pathways and telomerase activity; (5) oxidative stress, through Nrf2/ARE signalling, ROS elimination and catalase activity; and (6) efficacy of chemotherapeutic agents, such as oxaliplatin, etoposide and doxorubicin. In addition, the need to enhance the bioavailability and delivery of mangiferin are briefly addressed, as well as the potential for toxicity. PMID- 27367722 TI - Supplementation of Reduced Gluten Barley Diet with Oral Prolyl Endopeptidase Effectively Abrogates Enteropathy-Associated Changes in Gluten-Sensitive Macaques. AB - Celiac disease (CD) is an autoimmune disorder that affects approximately three million people in the United States. Furthermore, non-celiac gluten sensitivity (NCGS) affects an estimated additional 6% of the population, e.g., 20 million in the U.S. The only effective treatment of CD and NCGS requires complete removal of gluten sources from the diet. While required adherence to a gluten-free diet (GFD) is extremely difficult to accomplish, efforts to develop additional supportive treatments are needed. To facilitate these efforts, we developed a gluten-sensitive (GS) rhesus macaque model to study the effects of novel therapies. Recently reported results from phase one of this project suggest that partial improvement-but not remission-of gluten-induced disease can be accomplished by 100-fold reduction of dietary gluten, i.e., 200 ppm-by replacement of conventional dietary sources of gluten with a mutant, reduced gluten (RG) barley (lys3a)-derived source. The main focus of this (phase two) study was to determine if the inflammatory effects of the residual gluten in lys3a mutant barley grain could be further reduced by oral supplementation with a prolylendopeptidase (PE). Results reveal that PE supplementation of RG barley diet induces more complete immunological, histopathological and clinical remission than RG barley diet alone. The combined effects of RG barley diet and PE supplementation resulted in a further decrease of inflammatory mediators IFN gamma and TNF secretion by peripheral lymphocytes, as well as decreased plasma anti-gliadin and anti-intestinal tissue transglutaminase (TG2) antibodies, diminished active caspase production in small intestinal mucosa, and eliminated clinical diarrhea-all comparable with a gluten-free diet induced remission. In summary, the beneficial results of a combined RG barley and PE administration in GS macaques may warrant the investigation of similar synergistic approaches. PMID- 27367723 TI - An Intervention with Mineral Water Decreases Cardiometabolic Risk Biomarkers. A Crossover, Randomised, Controlled Trial with Two Mineral Waters in Moderately Hypercholesterolaemic Adults. AB - Water intake is essential for health maintenance and disease prevention. The effects of an intervention with two mineral waters, sodium-bicarbonated mineral water (BW) or control mineral water low in mineral content (CW), on cardiometabolic risk biomarkers were studied. In a randomised-controlled crossover-trial, sixty-four moderately hypercholesterolaemic adults were randomly assigned to consume 1 L/day of either BW (sodium, 1 g/L; bicarbonate, 2 g/L) or CW with the main meals for eight weeks, separated by an eight-week washout period. Blood lipids, lipid oxidation, glucose, insulin, aldosterone, urine pH, urinary electrolytes, blood pressure, body weight, fluid intake, energy, and nutrients from total diet and beverages were determined. Total cholesterol, LDL cholesterol, and glucose decreased (p < 0.01), oxidised LDL tended to decrease (p = 0.073), and apolipoprotein B increased during the intervention, without water type effect. Energy and carbohydrates from beverages decreased since soft drinks and fruit juice consumptions decreased throughout the trial. BW increased urinary pH (p = 0.006) and reduced calcium/creatinine excretion (p = 0.011). Urinary potassium/creatinine decreased with both waters. Consumption of 1 L/day of mineral water with the main meals reduces cardiometabolic risk biomarkers, likely to be attributed to a replacement of soft drinks by water. In addition, BW does not affect blood pressure and exerts a moderate alkalizing effect in the body. PMID- 27367725 TI - Leucine-Enriched Essential Amino Acids Augment Mixed Protein Synthesis, But Not Collagen Protein Synthesis, in Rat Skeletal Muscle after Downhill Running. AB - Mixed and collagen protein synthesis is elevated for as many as 3 days following exercise. Immediately after exercise, enhanced amino acid availability increases synthesis of mixed muscle protein, but not muscle collagen protein. However, the potential for synergic effects of amino acid ingestion with exercise on both mixed and collagen protein synthesis remains unclear. We investigated muscle collagen protein synthesis in rats following post-exercise ingestion of leucine enriched essential amino acids. We determined fractional protein synthesis rates (FSR) at different time points following exercise. Mixed protein and collagen protein FSRs in skeletal muscle were determined by measuring protein-bound enrichments of hydroxyproline and proline, and by measuring the intracellular enrichment of proline, using injections of flooding d3-proline doses. A leucine enriched mixture of essential amino acids (or distilled water as a control) was administrated 30 min or 1 day post-exercise. The collagen protein synthesis in the vastus lateralis was elevated for 2 days after exercise. Although amino acid administration did not increase muscle collagen protein synthesis, it did lead to augmented mixed muscle protein synthesis 1 day following exercise. Thus, contrary to the regulation of mixed muscle protein synthesis, muscle collagen protein synthesis is not affected by amino acid availability after damage-inducing exercise. PMID- 27367724 TI - Beneficial Effect of Synbiotic Supplementation on Hepatic Steatosis and Anthropometric Parameters, But Not on Gut Permeability in a Population with Nonalcoholic Steatohepatitis. AB - Nonalcoholic fatty liver disease is the most prevalent chronic liver disease in Western countries; it can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocarcinoma. The importance of gut-liver-adipose tissue axis has become evident and treatments targeting gut microbiota may improve inflammatory and metabolic parameters in NASH patients. In a randomized, controlled clinical trial, involving 50 biopsy-proven NASH patients, we investigated the effects of synbiotic supplementation on metabolic parameters, hepatic steatosis, intestinal permeability, small intestinal bacterial overgrowth (SIBO) and lipopolysaccharide (LPS) serum levels. Patients were separated into two groups receiving Lactobacillus reuteri with guar gum and inulin for three months and healthy balanced nutritional counseling versus nutritional counseling alone. Before and after the intervention we assessed steatosis by magnetic resonance imaging, intestinal permeability by lactulose/mannitol urinary excretion and SIBO by glucose breath testing. NASH patients presented high gut permeability, but low prevalence of SIBO. After the intervention, only the synbiotic group presented a reduction in steatosis, lost weight, diminished BMI and waist circumference measurement. Synbiotic did not improve intestinal permeability or LPS levels. We concluded that synbiotic supplementation associated with nutritional counseling seems superior to nutritional counseling alone for NASH treatment as it attenuates steatosis and may help to achieve weight loss. PMID- 27367727 TI - Reply to O. Osibogun's Letter to the Editor Re: Hess S. et al.; Nutrients 2016, 8, 88. AB - In a recent literature review and meta-analysis, we summarized the evidence of reducing anemia in children and adults with fortified condiments and noodles [1].[...]. PMID- 27367726 TI - The Effects of Low-Carbohydrate Diets on Psychosocial Outcomes in Obesity/Overweight: A Systematic Review of Randomized, Controlled Studies. AB - BACKGROUND: Little is known about the relative psychosocial effects of carbohydrate reduction in comparison to other weight-loss diets in subjects receiving treatment for obesity/overweight. We, therefore, set out to conduct a systematic review of the psychosocial outcomes of such patients, treated by means of either a low-carbohydrate diet or an isocaloric diet of other macronutrient composition. METHODS: Literature searches, study selection, method development, and quality appraisal were performed independently by two authors, and data were synthesized using a narrative approach, in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. RESULTS: Eight randomized controlled studies met the inclusion criteria, and their subsequent analysis revealed that improvements in psychological and social outcomes do occur during short- and long-term weight loss programmes, but that low-carbohydrate diets have no greater effect on psychosocial outcomes when compared to diets of different macronutrient composition at either short- or long term follow-up (one-year). However, the lack of studies with longer duration follow-up, and the absence of data in the adolescent population limit the generalizability of our findings. CONCLUSION: The short- and long-term improvements in psychosocial outcomes seen in patients undergoing weight-loss treatment appear to be independent of the macronutrient composition of their diet. PMID- 27367728 TI - Liquid Chromatography with a Fluorimetric Detection Method for Analysis of Paralytic Shellfish Toxins and Tetrodotoxin Based on a Porous Graphitic Carbon Column. AB - Paralytic shellfish toxins (PST) traditionally have been analyzed by liquid chromatography with either pre- or post-column derivatization and always with a silica-based stationary phase. This technique resulted in different methods that need more than one run to analyze the toxins. Furthermore, tetrodotoxin (TTX) was recently found in bivalves of northward locations in Europe due to climate change, so it is important to analyze it along with PST because their signs of toxicity are similar in the bioassay. The methods described here detail a new approach to eliminate different runs, by using a new porous graphitic carbon stationary phase. Firstly we describe the separation of 13 PST that belong to different groups, taking into account the side-chains of substituents, in one single run of less than 30 min with good reproducibility. The method was assayed in four shellfish matrices: mussel (Mytillus galloprovincialis), clam (Pecten maximus), scallop (Ruditapes decussatus) and oyster (Ostrea edulis). The results for all of the parameters studied are provided, and the detection limits for the majority of toxins were improved with regard to previous liquid chromatography methods: the lowest values were those for decarbamoyl-gonyautoxin 2 (dcGTX2) and gonyautoxin 2 (GTX2) in mussel (0.0001 mg saxitoxin (STX).diHCl kg(-1) for each toxin), decarbamoyl-saxitoxin (dcSTX) in clam (0.0003 mg STX.diHCl kg(-1)), N sulfocarbamoyl-gonyautoxins 2 and 3 (C1 and C2) in scallop (0.0001 mg STX.diHCl kg(-1) for each toxin) and dcSTX (0.0003 mg STX.diHCl kg(-1) ) in oyster; gonyautoxin 2 (GTX2) showed the highest limit of detection in oyster (0.0366 mg STX.diHCl kg(-1)). Secondly, we propose a modification of the method for the simultaneous analysis of PST and TTX, with some minor changes in the solvent gradient, although the detection limit for TTX does not allow its use nowadays for regulatory purposes. PMID- 27367729 TI - Optimizing the Detection of Circulating Markers to Aid in Early Lung Cancer Detection. AB - Improving early detection of lung cancer is critical to improving lung cancer survival. Studies have shown that computerized tomography (CT) screening can reduce mortality from lung cancer, but this involves risks of radiation exposure and can identify non-cancer lung nodules that lead to unnecessary interventions for some. There is a critical need to develop alternative, less invasive methods to identify patients who have early-stage lung cancer. The detection of circulating tumor cells (CTCs) are a promising area of research, but current technology is limited by a low yield of CTCs. Alternate studies are investigating circulating nucleic acids and proteins as possible tumor markers. It is critical to develop innovative methods for early lung cancer detection that may include CTCs or other markers that are low-risk and low-cost, yet specific and sensitive, to facilitate improved survival by diagnosing the disease when it is surgically curable. PMID- 27367730 TI - Modulating Dickkopf-1: A Strategy to Monitor or Treat Cancer? AB - Dickkopf-1 (DKK1) is a secreted Wnt/beta-catenin pathway antagonist involved in embryogenesis. It was first described 25 years ago for its function in head induction and limb morphogenesis. Since then, this protein has been widely studied in the context of active Wnt/beta-catenin signalling during cellular differentiation and development. Dysregulation of DKK1 has been associated with bone pathologies and has now emerged as a potential biomarker of cancer progression and prognosis for several types of malignancies. Reducing the amount of circulating DKK1 may reveal a simple and efficient strategy to limit or reverse cancer growth. This review will provide an overview of the role of Dickkopf-1 in cancer and explore its potential use as a biomarker and therapeutic target. PMID- 27367731 TI - Advancing Clostridia to Clinical Trial: Past Lessons and Recent Progress. AB - Most solid cancers contain regions of necrotic tissue. The extent of necrosis is associated with poor survival, most likely because it reflects aggressive tumour outgrowth and inflammation. Intravenously injected spores of anaerobic bacteria from the genus Clostridium infiltrate and selectively germinate in these necrotic regions, providing cancer-specific colonisation. The specificity of this system was first demonstrated over 60 years ago and evidence of colonisation has been confirmed in multiple tumour models. The use of "armed" clostridia, such as in Clostridium Directed Enzyme Prodrug Therapy (CDEPT), may help to overcome some of the described deficiencies of using wild-type clostridia for treatment of cancer, such as tumour regrowth from a well-vascularised outer rim of viable cells. Successful preclinical evaluation of a transferable gene that metabolises both clinical stage positron emission tomography (PET) imaging agents (for whole body vector visualisation) as well as chemotherapy prodrugs (for conditional enhancement of efficacy) would be a valuable early step towards the prospect of "armed" clostridia entering clinical evaluation. The ability to target the immunosuppressive hypoxic tumour microenvironment using CDEPT may offer potential for synergy with recently developed immunotherapy strategies. Ultimately, clostridia may be most efficacious when combined with conventional therapies, such as radiotherapy, that sterilise viable aerobic tumour cells. PMID- 27367732 TI - Human Specific Regulation of the Telomerase Reverse Transcriptase Gene. AB - Telomerase, regulated primarily by the transcription of its catalytic subunit telomerase reverse transcriptase (TERT), is critical for controlling cell proliferation and tissue homeostasis by maintaining telomere length. Although there is a high conservation between human and mouse TERT genes, the regulation of their transcription is significantly different in these two species. Whereas mTERT expression is widely detected in adult mice, hTERT is expressed at extremely low levels in most adult human tissues and cells. As a result, mice do not exhibit telomere-mediated replicative aging, but telomere shortening is a critical factor of human aging and its stabilization is essential for cancer development in humans. The chromatin environment and epigenetic modifications of the hTERT locus, the binding of transcriptional factors to its promoter, and recruitment of nucleosome modifying complexes all play essential roles in restricting its transcription in different cell types. In this review, we will discuss recent progress in understanding the molecular mechanisms of TERT regulation in human and mouse tissues and cells, and during cancer development. PMID- 27367733 TI - Beneficial Insect Attraction to Milkweeds (Asclepias speciosa, Asclepias fascicularis) in Washington State, USA. AB - Native plant and beneficial insect associations are relatively unstudied yet are important in native habitat restoration programs for improving and sustaining conservation biological control of arthropod pests in agricultural crops. Milkweeds (Asclepias spp.) are currently the focus of restoration programs in the USA aimed at reversing a decline in populations of the milkweed-dependent monarch butterfly (Danaus plexippus); however, little is known of the benefits of these plants to other beneficial insects. Beneficial insects (predators, parasitoids, pollinators) attracted to two milkweed species (Asclepias speciosa, Asclepias fascicularis) in central Washington State, WA, USA were identified and counted on transparent sticky traps attached to blooms over five seasons. Combining all categories of beneficial insects, means of 128 and 126 insects per trap were recorded for A. speciosa and A. fascicularis, respectively. Predatory and parasitic flies dominated trap catches for A. speciosa while parasitic wasps were the most commonly trapped beneficial insects on A. fascicularis. Bees were trapped commonly on both species, especially A. speciosa with native bees trapped in significantly greater numbers than honey bees. Beneficial insect attraction to A. speciosa and A. fascicularis was substantial. Therefore, these plants are ideal candidates for habitat restoration, intended to enhance conservation biological control, and for pollinator conservation. In central Washington, milkweed restoration programs for enhancement of D. plexippus populations should also provide benefits for pest suppression and pollinator conservation. PMID- 27367734 TI - Viral Inhibition of the IFN-Induced JAK/STAT Signalling Pathway: Development of Live Attenuated Vaccines by Mutation of Viral-Encoded IFN-Antagonists. AB - The interferon (IFN) induced anti-viral response is amongst the earliest and most potent of the innate responses to fight viral infection. The induction of the Janus kinase/signal transducer and activation of transcription (JAK/STAT) signalling pathway by IFNs leads to the upregulation of hundreds of interferon stimulated genes (ISGs) for which, many have the ability to rapidly kill viruses within infected cells. During the long course of evolution, viruses have evolved an extraordinary range of strategies to counteract the host immune responses in particular by targeting the JAK/STAT signalling pathway. Understanding how the IFN system is inhibited has provided critical insights into viral virulence and pathogenesis. Moreover, identification of factors encoded by viruses that modulate the JAK/STAT pathway has opened up opportunities to create new anti viral drugs and rationally attenuated new generation vaccines, particularly for RNA viruses, by reverse genetics. PMID- 27367737 TI - A Review of Glass-Ionomer Cements for Clinical Dentistry. AB - This article is an updated review of the published literature on glass-ionomer cements and covers their structure, properties and clinical uses within dentistry, with an emphasis on findings from the last five years or so. Glass ionomers are shown to set by an acid-base reaction within 2-3 min and to form hard, reasonably strong materials with acceptable appearance. They release fluoride and are bioactive, so that they gradually develop a strong, durable interfacial ion-exchange layer at the interface with the tooth, which is responsible for their adhesion. Modified forms of glass-ionomers, namely resin modified glass-ionomers and glass carbomer, are also described and their properties and applications covered. Physical properties of the resin-modified glass-ionomers are shown to be good, and comparable with those of conventional glass-ionomers, but biocompatibility is somewhat compromised by the presence of the resin component, 2 hydroxyethyl methacrylate. Properties of glass carbomer appear to be slightly inferior to those of the best modern conventional glass ionomers, and there is not yet sufficient information to determine how their bioactivity compares, although they have been formulated to enhance this particular feature. PMID- 27367736 TI - Heart Failure: Diagnosis, Management and Utilization. AB - Despite the advancement in medicine, management of heart failure (HF), which usually presents as a disease syndrome, has been a challenge to healthcare providers. This is reflected by the relatively higher rate of readmissions along with increased mortality and morbidity associated with HF. In this review article, we first provide a general overview of types of HF pathogenesis and diagnostic features of HF including the crucial role of exercise in determining the severity of heart failure, the efficacy of therapeutic strategies and the morbidity/mortality of HF. We then discuss the quality control measures to prevent the growing readmission rates for HF. We also attempt to elucidate published and ongoing clinical trials for HF in an effort to evaluate the standard and novel therapeutic approaches, including stem cell and gene therapies, to reduce the morbidity and mortality. Finally, we discuss the appropriate utilization/documentation and medical coding based on the severity of the HF alone and with minor and major co-morbidities. We consider that this review provides an extensive overview of the HF in terms of disease pathophysiology, management and documentation for the general readers, as well as for the clinicians/physicians/hospitalists. PMID- 27367735 TI - Mechanisms of TGFbeta-Induced Epithelial-Mesenchymal Transition. AB - Transitory phenotypic changes such as the epithelial-mesenchymal transition (EMT) help embryonic cells to generate migratory descendants that populate new sites and establish the distinct tissues in the developing embryo. The mesenchymal descendants of diverse epithelia also participate in the wound healing response of adult tissues, and facilitate the progression of cancer. EMT can be induced by several extracellular cues in the microenvironment of a given epithelial tissue. One such cue, transforming growth factor beta (TGFbeta), prominently induces EMT via a group of specific transcription factors. The potency of TGFbeta is partly based on its ability to perform two parallel molecular functions, i.e. to induce the expression of growth factors, cytokines and chemokines, which sequentially and in a complementary manner help to establish and maintain the EMT, and to mediate signaling crosstalk with other developmental signaling pathways, thus promoting changes in cell differentiation. The molecules that are activated by TGFbeta signaling or act as cooperating partners of this pathway are impossible to exhaust within a single coherent and contemporary report. Here, we present selected examples to illustrate the key principles of the circuits that control EMT under the influence of TGFbeta. PMID- 27367738 TI - Amperometric Biosensor Based on Zirconium Oxide/Polyethylene Glycol/Tyrosinase Composite Film for the Detection of Phenolic Compounds. AB - A phenolic biosensor based on a zirconium oxide/polyethylene glycol/tyrosinase composite film for the detection of phenolic compounds has been explored. The formation of the composite film was expected via electrostatic interaction between hexacetyltrimethylammonium bromide (CTAB), polyethylene glycol (PEG), and zirconium oxide nanoparticles casted on screen printed carbon electrode (SPCE). Herein, the electrode was treated by casting hexacetyltrimethylammonium bromide on SPCE to promote a positively charged surface. Later, zirconium oxide was mixed with polyethylene glycol and the mixture was dropped cast onto the positively charged SPCE/CTAB. Tyrosinase was further immobilized onto the modified SPCE. Characterization of the prepared nanocomposite film and the modified SPCE surface was investigated by scanning electron microscopy (SEM), Electrochemical Impedance Spectroscopy (EIS), and Cyclic voltamogram (CV). The developed biosensor exhibits rapid response for less than 10 s. Two linear calibration curves towards phenol in the concentrations ranges of 0.075-10 uM and 10-55 uM with the detection limit of 0.034 uM were obtained. The biosensor shows high sensitivity and good storage stability for at least 30 days. PMID- 27367739 TI - Ribosomal Antibiotics: Contemporary Challenges. AB - Most ribosomal antibiotics obstruct distinct ribosomal functions. In selected cases, in addition to paralyzing vital ribosomal tasks, some ribosomal antibiotics are involved in cellular regulation. Owing to the global rapid increase in the appearance of multi-drug resistance in pathogenic bacterial strains, and to the extremely slow progress in developing new antibiotics worldwide, it seems that, in addition to the traditional attempts at improving current antibiotics and the intensive screening for additional natural compounds, this field should undergo substantial conceptual revision. Here, we highlight several contemporary issues, including challenging the common preference of broad range antibiotics; the marginal attention to alterations in the microbiome population resulting from antibiotics usage, and the insufficient awareness of ecological and environmental aspects of antibiotics usage. We also highlight recent advances in the identification of species-specific structural motifs that may be exploited for the design and the creation of novel, environmental friendly, degradable, antibiotic types, with a better distinction between pathogens and useful bacterial species in the microbiome. Thus, these studies are leading towards the design of "pathogen-specific antibiotics," in contrast to the current preference of broad range antibiotics, partially because it requires significant efforts in speeding up the discovery of the unique species motifs as well as the clinical pathogen identification. PMID- 27367741 TI - Inhibitors of programmed cell death 1 (PD-1): a patent review (2010-2015). PMID- 27367740 TI - Aberrant Glycosylation of Anchor-Optimized MUC1 Peptides Can Enhance Antigen Binding Affinity and Reverse Tolerance to Cytotoxic T Lymphocytes. AB - Cancer vaccines have often failed to live up to their promise, although recent results with checkpoint inhibitors are reviving hopes that they will soon fulfill their promise. Although mutation-specific vaccines are under development, there is still high interest in an off-the-shelf vaccine to a ubiquitous antigen, such as MUC1, which is aberrantly expressed on most solid and many hematological tumors, including more than 90% of breast carcinomas. Clinical trials for MUC1 have shown variable success, likely because of immunological tolerance to a self antigen and to poor immunogenicity of tandem repeat peptides. We hypothesized that MUC1 peptides could be optimized, relying on heteroclitic optimizations of potential anchor amino acids with and without tumor-specific glycosylation of the peptides. We have identified novel MUC1 class I peptides that bind to HLA-A*0201 molecules with significantly higher affinity and function than the native MUC1 peptides. These peptides elicited CTLs from normal donors, as well as breast cancer patients, which were highly effective in killing MUC1-expressing MCF-7 breast cancer cells. Each peptide elicited lytic responses in greater than 6/8 of normal individuals and 3/3 breast cancer patients. The CTLs generated against the glycosylated-anchor modified peptides cross reacted with the native MUC1 peptide, STAPPVHNV, suggesting these analog peptides may offer substantial improvement in the design of epitope-based vaccines. PMID- 27367742 TI - Public attitudes toward stuttering in Europe: Within-country and between-country comparisons. AB - INTRODUCTION: Epidemiological research methods have been shown to be useful in determining factors that might predict commonly reported negative public attitudes toward stuttering. Previous research has suggested that stuttering attitudes of respondents from North America and Europe (i.e., "The West"), though characterized by stereotypes and potential stigma, are more positive than those from several other regions of the world. This inference assumes that public attitudes within various regions characterized by "The West" are similar. PURPOSE: This study aimed to determine the extent to which public stuttering attitudes are similar or different both within regions of three different European countries and between or among five different European countries or similar geographic areas. It also aimed to compare these European attitudes to attitudes from 135 samples around the world using a standard measure. MATERIAL AND METHODS: Using convenience sampling, 1111 adult respondents from eight different investigations completed the Public Opinion Survey of Human Attributes Stuttering (POSHA-S) in the dominant language of each country or area. In Study I, the authors compared attitudes within three different regions of Bosnia & Herzegovina, Italy, and Norway. In Study II, the authors compared attitudes between combined samples from Bosnia & Herzegovina, Italy, and Norway (with additional respondents from Sweden), and two other samples, one from Germany and the other from Ireland and England. RESULTS: Attitudes of adults from the three samples within Bosnia & Herzegovina, Italy, and Norway were remarkably similar. By contrast, attitudes between the five different countries or area were quite dramatically different. Demographic variables on the POSHA-S did not predict the rank order of these between-country/area differences. Compared to the POSHA-S worldwide database, European attitudes ranged from less positive than average (i.e., Italians) to more positive than average (i.e., Norwegians and Swedes). CONCLUSION: Factors related to national identity appear to play a significant role in differences in public attitudes in Europe and should be explored in future research. PMID- 27367743 TI - Ocular hypotensive effect of fixed-combination brinzolamide/brimonidine adjunctive to a prostaglandin analog: a randomized clinical trial. AB - PurposeTo determine whether intraocular pressure (IOP) lowering with fixed combination brinzolamide/brimonidine (BBFC) adjunctive to a prostaglandin analog (PGA) was superior to that of vehicle+PGA in patients with open-angle glaucoma or ocular hypertension who were inadequately controlled with PGA monotherapyMethodsThis 6-week, multicenter, randomized, double-masked, parallel group trial was conducted at 30 clinical sites in the United States between October 2013 and May 2014. Eligible patients were adults with open-angle glaucoma or ocular hypertension and with mean IOP >=21 and <32 mm Hg, whereas receiving an open-label PGA (latanoprost, bimatoprost, or travoprost). Patients instilled a PGA once-daily in a run-in phase before randomization to masked BBFC or vehicle adjunctive treatment. Masked treatments were instilled 3 times daily for 6 weeks, and patients continued once-daily use of their PGA. The primary efficacy end point was the between-group difference in mean diurnal IOP (average of 0800, 1000, 1500, and 1700 hours time points) at week 6.ResultsAt week 6, mean diurnal IOP with BBFC+PGA was lower than with vehicle+PGA (17.1+/-0.4 mm Hg vs 20.5+/-0.4 mm Hg; between-group difference, -3.4+/-0.5 mm Hg; P<0.0001; 95% confidence interval, -4.5 to -2.4 mm Hg). BBFC+PGA reduced mean diurnal IOP by 5.7 mm Hg (25%) from the baseline IOP achieved with PGA monotherapy.ConclusionsTherapy with BBFC produced an additive IOP-lowering effect compared with a PGA alone or in conjunction with vehicle. BBFC may provide an effective treatment option for patients receiving PGA monotherapy who require additional IOP reduction. PMID- 27367744 TI - Risk factors for intraoperative floppy iris syndrome: a prospective study. AB - PurposeTo evaluate risk factors for intraoperative floppy iris syndrome (IFIS) in patients undergoing phacoemulsification.MethodsParticipants in the study were 1274 consecutive patients, who underwent routine phacoemulsification cataract surgery. The following data were recorded and evaluated as possible risk factors: ophthalmological conditions, axial length of the eye, sociodemographic features, clinical data (hypertension and diabetes mellitus), medications being taken at the time of surgery, and duration of their intake. Cases were characterized intraoperatively as IFIS and non-IFIS. Univariate and multivariate logistic regression analysis were performed.ResultsIFIS was observed in 63/1274 eyes (4.9%, 95% CI: 3.9-6.7%). Current use of tamsulosin, alfuzosin, terazosin, benzodiazepines, quetiapine, and finasteride, as well as hypertension, were all independently associated with IFIS. Significant associations were noted for male sex, rivastigmine, and short axial length, which did not reach significance at the multivariate analysis. Duration of alpha-blockers intake was not found to be associated with IFIS.ConclusionApart from the well-established associations with alpha-blockers, this prospective study points to benzodiazepines, quetiapine, finasteride, and hypertension as potential risk factors for IFIS. Short axial length and rivastigmine were significantly associated with IFIS only at the univariate analysis. PMID- 27367745 TI - Difluprednate versus prednisolone acetate for inflammation following cataract surgery in pediatric patients: a randomized safety and efficacy study. AB - PurposeTo evaluate safety and efficacy of difluprednate 0.05% ophthalmic emulsion for treatment of postoperative inflammation after cataract surgery in pediatric patients.MethodsThis was a phase 3B, multicentre, randomized, double-masked, active-controlled study of patients aged 0-3 years who underwent uncomplicated cataract surgery in one eye, with/without intraocular lens implantation. Patients were randomized to receive difluprednate 0.05% four times daily or prednisolone acetate 1% for 14 days post surgery, followed by tapering for 14 days. Safety included evaluation of adverse events. Primary efficacy was the proportion of patients with an anterior cell grade of 0 (no cells) at day 14; secondary efficacy was a global inflammation score.ResultsForty patients were randomized to each treatment group. Adverse drug reactions included corneal oedema (difluprednate 0.5%, n=1; prednisolone acetate 1%, n=0) and increased intraocular pressure or ocular hypertension (n=2/group). Mean intraocular pressure values during treatment were 2-3 mm Hg higher with difluprednate 0.05% compared with prednisolone acetate 1%; mean values were similar between groups by the first week after treatment cessation. At 2 weeks post surgery, the incidence of complete clearing of anterior chamber cells was similar between groups (difluprednate 0.05%, n=30 (78.9%); prednisolone acetate 1%, n=31 (77.5%). Compared with prednisolone acetate 1%, approximately twice as many difluprednate 0.05%-treated patients had a global inflammation assessment score indicating no inflammation on day 1 (n=12 (30.8%) vs n=7 (17.5%) and day 8 (n=18 (48.7%) vs n=10 (25.0%).ConclusionsDifluprednate 0.05% four times daily showed safety and efficacy profiles similar to prednisolone acetate 1% four times daily in children 0-3 years undergoing cataract surgery. PMID- 27367746 TI - Fibrin glue inhibits migration of ocular surface epithelial cells. AB - PurposeFibrin glue has been used successfully in numerous ophthalmic surgical procedures. Recently, fibrin glue has been used in limbal stem cell transplantation to reduce both operative time and to negate the need for sutures. The aim of this study was to determine the effects of fibrin glue on epithelial cell migration in vitro.MethodsCorneoscleral rims were split to retain the epithelial layer, Bowman's layer, and anterior stroma. Rims were cut into eight equal-sized pieces and were placed directly on culture plates or affixed with fibrin glue. Rims were maintained in culture for 25 days and epithelial cell growth was monitored. Cells were photographed to measure area or growth and immunofluorescence staining of explants for fibrin was performed.ResultsExplants that were glued demonstrated significantly delayed epithelial cell growth and migration as compared with explants without glue. By day 16, all fibrin glue had dissolved and coincided with onset of cell growth from glued explants. Cell growth commenced between days 3 and 4 for control explants without glue and around days 14-16 for explants with fibrin glue.ConclusionsFibrin glue delays epithelial cell migration by acting as a physical barrier and can potentially interfere with explant-derived limbal epithelial cell migration on to the corneal surface. We propose that glue should be used to attach the conjunctival frill of the limbal explant but care should be taken to ensure that the glue does not wrap around the explant if used to secure the explant as well. Strategic use of glue, to attach the recessed conjunctiva, can be advantageous in delaying conjunctival cell migration and reducing the need for sequential sector conjunctival epitheliectomy. PMID- 27367747 TI - Secondary intraocular lens implantation following infantile cataract surgery: intraoperative indications, postoperative outcomes. AB - PurposeThe purpose of this study was to determine the long-term complications and outcomes of secondary intraocular lens (IOL) implantation in patients with congenital cataracts.Patients and MethodsThe medical records of children operated for secondary IOL implantation surgery between 2000 and 2014 were retrospectively reviewed. Those who had undergone their initial congenital cataract surgery before 7 months of age were included and were analyzed for intra- and postoperative factors and postoperative refractive outcomes. We focused on three complications: visual axis opacification (VAO), glaucoma, and IOL exchange after at least 1 year of follow-up.ResultsA total of 49 eyes of 49 patients were analyzed for intraoperative indications. Of those, 37 eyes of 37 patients had at least 1 year of follow-up and were analyzed for postoperative outcomes. The mean age at secondary implantation was 55.2+/-21.6 months. At secondary implantation, 69.4% of eyes were implanted in the capsular bag, 28.6% in the sulcus, and 2.0% that were angle-supported. There was no significant correlation between the site of secondary IOL implantation and age at implantation (P=0.216). The mean follow up after implantation was 57.6+/-33.6 months. The rate of VAO was 5.4%, the rate of glaucoma occurring after secondary implantation was 16.2%, and the rate of IOL exchange was 2.7%. The median visual acuity at final follow-up was 20/40. For patients with unilateral cataracts it was 20/60 and for bilateral patients it was 20/30.ConclusionsThe secondary IOL implantation in children is a relatively safe procedure associated with low rates of postoperative complications. Visual outcomes are acceptable and are better for bilateral patients than for unilateral patients. PMID- 27367748 TI - Click Chemistry Immobilization of Antibodies on Polymer Coated Gold Nanoparticles. AB - The goal of this work is to develop an innovative approach for the coating of gold nanoparticles (AuNPs) with a synthetic functional copolymer. This stable coating with a thickness of few nanometers provides, at the same time, stabilization and functionalization of the particles. The polymeric coating consists of a backbone of polydimethylacrylamide (DMA) functionalized with an alkyne monomer that allows the binding of azido modified molecules by Cu(I) catalyzed azide/alkyne 1,3-dipolar cycloaddition (CuAAC, click chemistry). The thin polymer layer on the surface stabilizes the colloidal suspension whereas the alkyne functions pending from the backbone are available for the reaction with azido-modified proteins. The reactivity of the coating is demonstrated by immobilizing an azido modified anti-mouse IgG antibody on the particle surface. This approach for the covalent binding of antibody to a gold-NPs is applied to the development of gold labels in biosensing techniques. PMID- 27367749 TI - Effect of Generic Competition on Atorvastatin Prescribing and Patients' Out-of Pocket Spending. AB - IMPORTANCE: In November 2011, the cholesterol level-lowering medication atorvastatin calcium became available in the United States as a generic drug. However, only a single generic form (from a manufacturer that qualified for market exclusivity by challenging several of Pfizer's patents) and an authorized generic form (a brand-name drug sold as a generic) were available for the first 180 days. OBJECTIVE: To describe trends in the prescribing of generic atorvastatin after expiration of market exclusivity for the brand-name medication and the effect on patients' out-of-pocket spending. DESIGN, SETTING, AND PARTICIPANTS: A US population-based study used commercial claims data from the Optum Clinformatics research database (UnitedHealth Group) from December 1, 2010, to May 31, 2013. Participants were 1 968 709 adults with commercial insurance who had been prescribed 1 or more statins (13 285 223 statin prescriptions). An interrupted times series model was used to examine the effect of limited and full generic competition on brand-name and generic atorvastatin prescriptions. Data were analyzed from December 1, 2010, to May 31, 2013. EXPOSURES: Prescription of brand-name atorvastatin, generic atorvastatin, and authorized generic atorvastatin were distinguished using National Drug Codes. MAIN OUTCOMES AND MEASURES: Total number of prescriptions dispensed per month and out-of-pocket expenditures for a typical 30-day supply of 20-mg atorvastatin during the periods of brand-name availability only, limited generic competition (lasting 180 days after market exclusivity ended), and full generic competition. RESULTS: Of the 1 968 709 beneficiaries, 1 483 066 (58.8% male and 41.2% female; mean [SD] age, 55.6 [10.2] years) received a prescription for a single statin and were included in the analysis. The introduction of the first generic competitor was associated with a reduction in monthly brand-name atorvastatin fills by 20 896 prescriptions (level change, P = .001), an 18.1% change compared with the month preceding loss of exclusivity. Full generic competition reduced brand-name fills by 54 944 prescriptions (level change, P < .001), a 47.6% change relative to the month preceding loss of exclusivity. During the first 180 days of generic competition, no meaningful difference in monthly out-of-pocket spending was found between brand-name (median, $16.98; interquartile range [IQR], $8.76-$48.66) and generic (median, $19.98; IQR, $7.50-$54.90) atorvastatin. After full generic competition, estimated monthly out-of-pocket spending for generic atorvastatin (median $5.10; IQR, $3.36-$19.98) or authorized generic atorvastatin (median, $5.52; IQR, $3.48 $19.98) was substantially lower than that for brand-name atorvastatin (median, $30.00; IQR, $15.00-$91.38). CONCLUSIONS AND RELEVANCE: Among patients with commercial health insurance, delays in generic uptake and high levels of out-of pocket spending during the first 180 days after atorvastatin lost market exclusivity slowed changes in drug prescribing and decreases in patients' out-of pocket costs. PMID- 27367751 TI - Femtosecond Laser-Induced Upconversion Luminescence in Rare-Earth Ions by Nonresonant Multiphoton Absorption. AB - The upconversion luminescence of rare-earth ions has attracted considerable interest because of its important applications in photoelectric conversion, color display, laser device, multiplexed biolabeling, and security printing. Previous studies mainly explored the upconversion luminescence generation through excited state absorption, energy transfer upconversion, and photon avalanche under the continuous wave laser excitation. Here, we focus on the upconversion luminescence generation through a nonresonant multiphoton absorption by using the intense femtosecond pulsed laser excitation and study the upconversion luminescence intensity control by varying the femtosecond laser phase and polarization. We show that the upconversion luminescence of rare-earth ions under the intense femtosecond laser field excitation is easy to be obtained due to the nonresonant multiphoton absorption through the nonlinear interaction between light and matter, which is not available by the continuous wave laser excitation in previous works. We also show that the upconversion luminescence intensity can be effectively controlled by varying the femtosecond pulsed laser phase and polarization, which can open a new technological opportunity to generate and control the upconversion luminescence of rare-earth ions and also can be further extended to the relevant application areas. PMID- 27367750 TI - Failure of Calcineurin Inhibitor (Tacrolimus) Weaning Randomized Trial in Long Term Stable Kidney Transplant Recipients. AB - Long-term renal transplant outcome is limited by side effects of immunosuppressive drugs, particularly calcineurin inhibitor (CNI). We assumed that some patients selected for a "low immunological risk of rejection" could be eligible and benefit from a CNI weaning strategy. We designed a prospective, randomized, multicenter, double-blind placebo-controlled clinical study (Eudract: 2010-019574-33) to analyze the benefit-risk ratio of tacrolimus weaning on highly selected patients (>=4 years of transplantation, normal histology, stable graft function, no anti-HLA immunization). The primary endpoint was improvement of renal function. Fifty-two patients were scheduled in each treatment arm, placebo compared to the CNI maintenance arm. Only 10 patients were eligible and randomized. Five patients were assigned to the placebo arm and five were assigned to the tacrolimus maintenance arm. In the tacrolimus maintenance arm, all patients maintained stable graft function and no immunological events occurred. Contrastingly, in the placebo arm, all five patients had to reintroduce a full dose of tacrolimus since three of them presented an acute rejection episode (one humoral, one mixed, and one borderline) and two displayed anti-HLA antibodies without histological lesion (one donor-specific antibodies [DSA] and one non DSA). Clearly, tacrolimus withdrawal must be avoided even in long-term highly selective stable kidney recipients. PMID- 27367752 TI - Combinational effects of muscarinic receptor inhibition and beta3-adrenoceptor stimulation on neurogenic bladder dysfunction in rats with spinal cord injury. AB - AIMS: To investigate the effects of combined therapy with an anticholinergic agent and a beta3-adrenoceptor agonist on bladder dysfunction and proliferation related molecule expression in rats with spinal cord injury (SCI). METHODS: The spinal cord was transected at the level of T8-9 in female Sprague-Dawley rats, which were divided into four groups; A: Vehicle, B: 10 mg/kg/day of oxybutynin, C: 10 mg/kg/day of mirabegron, and D: combined administration of oxybutynin and mirabegron. Drugs were administered by oral gavage from 2 to 4 weeks after spinal cord transection. We evaluated urodynamic parameters and bladder tissue remodeling factors. RESULTS: Non-voiding contractions (NVCs) during the storage phase of cystometrograms tended to be decreased in all three treated groups with a significant reduction in group D versus A. Bladder compliance was improved, and intercontraction intervals, voided volume and bladder capacity were increased in group D. In all three treated groups (B-D), the expression of HIF1-alpha and TGF beta1 was decreased compared to group A. The expression of collagen-III and bFGF was decreased in groups B and D. The total bladder elastin level was increased in group D. CONCLUSIONS: The combination therapy of an anticholinergic agent and a beta3-adrenoceptor agonist elevated the bladder elastin level, reduced NVCs, and increased bladder compliance more effectively than the monotherapy in SCI rats. Thus, the combination therapy could be effective for the treatment of neurogenic bladder dysfunction including bladder remodeling. Neurourol. Urodynam. 36:1039 1045, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27367753 TI - Rapid de novo aneurysm formation after clipping of a ruptured middle cerebral artery aneurysm in an infant with an MYH11 mutation. AB - The authors report the case of a previously healthy 6-month-old girl who presented with right arm and leg stiffening consistent with seizure activity. An initial CT scan of the head demonstrated acute subarachnoid hemorrhage in the basal cisterns extending into the left sylvian fissure. Computed tomography angiography demonstrated a 7 * 6 * 5-mm saccular aneurysm of the inferior M2 division of the left middle cerebral artery. The patient underwent left craniotomy and microsurgical clip ligation with wrapping of the aneurysm neck because the vessel appeared circumferentially dysplastic in the region of the aneurysm. Postoperative angiography demonstrated a small remnant, sluggish distal flow, but no significant cerebral vasospasm. Fifty-five days after the initial aneurysm rupture, the patient presented again with an acute intraparenchymal hemorrhage of the left anterior temporal lobe. Angiogram revealed a circumferentially dysplastic superior division of the M2 branch, with a new 5 * 4 mm saccular aneurysm distinct from the first, with 2 smaller aneurysms distal to the new ruptured aneurysm. Endovascular parent vessel occlusion with Onyx was performed. Genetic testing revealed a mutation of the MYH11. To the authors' knowledge, this is the first report of rapid de novo aneurysm formation in an infant with an MYH11 mutation. The authors review the patient's clinical presentation and management and comprehensively review the literature on this topic. PMID- 27367754 TI - WITHDRAWN: Target-controlled infusion versus manually-controlled infusion of propofol for general anaesthesia or sedation in adults. PMID- 27367755 TI - Instrument for Predicting Early Stroke Recurrence: Ambiguity and Biases. PMID- 27367757 TI - The Bright Side: Winslow Homer. PMID- 27367765 TI - The Challenging Task of Improving the Recovery of ICU Survivors. PMID- 27367767 TI - Navigating the Dermatological Drug Cost Curve. PMID- 27367766 TI - Standardized Rehabilitation and Hospital Length of Stay Among Patients With Acute Respiratory Failure: A Randomized Clinical Trial. AB - IMPORTANCE: Physical rehabilitation in the intensive care unit (ICU) may improve the outcomes of patients with acute respiratory failure. OBJECTIVE: To compare standardized rehabilitation therapy (SRT) to usual ICU care in acute respiratory failure. DESIGN, SETTING, AND PARTICIPANTS: Single-center, randomized clinical trial at Wake Forest Baptist Medical Center, North Carolina. Adult patients (mean age, 58 years; women, 55%) admitted to the ICU with acute respiratory failure requiring mechanical ventilation were randomized to SRT (n=150) or usual care (n=150) from October 2009 through May 2014 with 6-month follow-up. INTERVENTIONS: Patients in the SRT group received daily therapy until hospital discharge, consisting of passive range of motion, physical therapy, and progressive resistance exercise. The usual care group received weekday physical therapy when ordered by the clinical team. For the SRT group, the median (interquartile range [IQR]) days of delivery of therapy were 8.0 (5.0-14.0) for passive range of motion, 5.0 (3.0-8.0) for physical therapy, and 3.0 (1.0-5.0) for progressive resistance exercise. The median days of delivery of physical therapy for the usual care group was 1.0 (IQR, 0.0-8.0). MAIN OUTCOMES AND MEASURES: Both groups underwent assessor-blinded testing at ICU and hospital discharge and at 2, 4, and 6 months. The primary outcome was hospital length of stay (LOS). Secondary outcomes were ventilator days, ICU days, Short Physical Performance Battery (SPPB) score, 36-item Short-Form Health Surveys (SF-36) for physical and mental health and physical function scale score, Functional Performance Inventory (FPI) score, Mini-Mental State Examination (MMSE) score, and handgrip and handheld dynamometer strength. RESULTS: Among 300 randomized patients, the median hospital LOS was 10 days (IQR, 6 to 17) for the SRT group and 10 days (IQR, 7 to 16) for the usual care group (median difference, 0 [95% CI, -1.5 to 3], P = .41). There was no difference in duration of ventilation or ICU care. There was no effect at 6 months for handgrip (difference, 2.0 kg [95% CI, -1.3 to 5.4], P = .23) and handheld dynamometer strength (difference, 0.4 lb [95% CI, -2.9 to 3.7], P = .82), SF-36 physical health score (difference, 3.4 [95% CI, -0.02 to 7.0], P = .05), SF-36 mental health score (difference, 2.4 [95% CI, -1.2 to 6.0], P = .19), or MMSE score (difference, 0.6 [95% CI, -0.2 to 1.4], P = .17). There were higher scores at 6 months in the SRT group for the SPPB score (difference, 1.1 [95% CI, 0.04 to 2.1, P = .04), SF-36 physical function scale score (difference, 12.2 [95% CI, 3.8 to 20.7], P = .001), and the FPI score (difference, 0.2 [95% CI, 0.04 to 0.4], P = .02). CONCLUSIONS AND RELEVANCE: Among patients hospitalized with acute respiratory failure, SRT compared with usual care did not decrease hospital LOS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00976833. PMID- 27367768 TI - Sharing of Data From Industry-Funded Registered Clinical Trials. PMID- 27367769 TI - Prenatal Vitamin D and Offspring Wheezing. PMID- 27367770 TI - Characteristics of Patients Dying With Cancer in Developed Countries. PMID- 27367771 TI - Prenatal Vitamin D and Offspring Wheezing. PMID- 27367772 TI - Prenatal Vitamin D and Offspring Wheezing--Reply. PMID- 27367773 TI - Characteristics of Patients Dying With Cancer in Developed Countries--Reply. PMID- 27367774 TI - Measuring and Improving Quality. PMID- 27367775 TI - Measuring and Improving Quality--Reply. PMID- 27367776 TI - Office Visits Prior to Screening Colonoscopy. PMID- 27367777 TI - Office Visits Prior to Screening Colonoscopy--Reply. PMID- 27367778 TI - Costs of Contraceptive Coverage Under the Affordable Care Act. PMID- 27367779 TI - The Centennial of the Stethoscope. PMID- 27367780 TI - HIV and ageing: improving quantity and quality of life. AB - PURPOSE OF REVIEW: Evidence-based strategies are needed to address the growing complexity of care of those ageing with HIV so that as life expectancy is extended, quality of life is also enhanced. RECENT FINDINGS: Modifiable contributing factors to the quantity and quality of life in adults ageing with HIV include: burden of harmful health behaviours, injury from HIV infection, HIV treatment toxicity and general burden of age-associated comorbidities. In turn, these factors contribute to geriatric syndromes including multimorbidity and polypharmacy, physiologic frailty, falls and fragility fractures and cognitive dysfunction, which further compromise the quality of life long before they lead to mortality. SUMMARY: Viral suppression of HIV with combination antiviral therapy has led to increasing longevity but has not enabled a complete return to health among ageing HIV-infected individuals (HIV+). As adults age with HIV, the role of HIV itself and associated inflammation, effects of exposure to antiretroviral agents, the high prevalence of modifiable risk factors for age associated conditions (e.g. smoking), and the effects of other viral coinfections are all influencing the health trajectory of persons ageing with HIV. We must move from the simplistic notion of HIV becoming a 'chronic controllable illness' to understanding the continually evolving 'treated' history of HIV infection with the burden of age-associated conditions and geriatric syndromes in the context of an altered and ageing immune system. PMID- 27367782 TI - Relationship between Age and Retinal Nerve Fiber Layer Thickness in Normal Children. AB - PURPOSE: To evaluate the effect of age and ocular factors on peripapillary retinal nerve fiber layer (RNFL) thickness in children. METHOD: A total of 198 normal subjects aged <19 years received a comprehensive ophthalmologic examination, including measurement of visual acuity, axial length, and cycloplegic refraction. Fast optical coherence tomography RNFL scans were obtained and average RNFL thickness was adjusted for ocular magnification. One eye of each subject was randomly selected as the study eye. The correlations between age and other ocular variables were examined. RESULTS: Mean subject age was 8.61 +/- 3.12 years. Average RNFL thickness and ocular magnification corrected average RNFL thickness were 107.71 +/- 11.83 and 103.03 +/- 12.53 MUm, respectively. There was no significant correlation between observed RNFL thickness and spherical equivalent of the refractive error (SE), axial length, or age (all P >0.05). Corrected RNFL thickness was positively correlated with age and axial length and negatively correlated with SE (P <0.01). Age was negatively correlated with the percent difference between observed and corrected RNFL thickness (P <0.001). Multivariate linear regression analysis showed that both axial length and age were correlated with corrected RNFL thickness in subjects <15 years old (P <0.05). CONCLUSION: The RNFL thickness is likely to be overestimated in children <15 years old. Additionally, an RNFL thickness increase was observed in children <15 years old. Thus, ocular magnification and RNFL thickness increase should be considered when assessing RNFL thickness in patients <15 years old. PMID- 27367783 TI - The role of functional variability in a whole body co-ordinated movement - Application to high bar giant circles. AB - When performing a giant circle on high bar a gymnast flexes at the hips in the lower part of the circle, increasing the kinetic energy, and extends in the upper part of the circle, decreasing the kinetic energy. In order to perform a sequence of giant circles at even tempo, any variation in angular velocity at the end of the flexion phase needs to be reduced by the end of the extension phase. The aim of this study was to determine the nature and contribution of such adjustments. A computer simulation model of a gymnast performing giant circles on high bar was used to investigate strategies of (a) fixed timing of the extension phase (feedforward control) and (b) stretched timing in order to extend at the same point of the giant circle (feedforward with additional feedback control). For three elite gymnasts fixed timing reduced the angular velocity variation on average by 36% whereas stretched timing reduced the variation by 63%. The mean reduction for the actual gymnast techniques was 61%. It was concluded that both feedforward and feedback control strategies are used by gymnasts for controlling such movements. PMID- 27367781 TI - Genetics and Genomics of Longitudinal Lung Function Patterns in Individuals with Asthma. AB - RATIONALE: Patterns of longitudinal lung function growth and decline in childhood asthma have been shown to be important in determining risk for future respiratory ailments including chronic airway obstruction and chronic obstructive pulmonary disease. OBJECTIVES: To determine the genetic underpinnings of lung function patterns in subjects with childhood asthma. METHODS: We performed a genome-wide association study of 581 non-Hispanic white individuals with asthma that were previously classified by patterns of lung function growth and decline (normal growth, normal growth with early decline, reduced growth, and reduced growth with early decline). The strongest association was also measured in two additional cohorts: a small asthma cohort and a large chronic obstructive pulmonary disease metaanalysis cohort. Interaction between the genomic region encompassing the most strongly associated single-nucleotide polymorphism and nearby genes was assessed by two chromosome conformation capture assays. MEASUREMENTS AND MAIN RESULTS: An intergenic single-nucleotide polymorphism (rs4445257) on chromosome 8 was strongly associated with the normal growth with early decline pattern compared with all other pattern groups (P = 6.7 * 10-9; odds ratio, 2.8; 95% confidence interval, 2.0-4.0); replication analysis suggested this variant had opposite effects in normal growth with early decline and reduced growth with early decline pattern groups. Chromosome conformation capture experiments indicated a chromatin interaction between rs4445257 and the promoter of the distal CSMD3 gene. CONCLUSIONS: Early decline in lung function after normal growth is associated with a genetic polymorphism that may also protect against early decline in reduced growth groups. Clinical trial registered with www.clinicaltrials.gov (NCT00000575). PMID- 27367784 TI - Comprehensive quantitative investigation of arm swing during walking at various speed and surface slope conditions. AB - Previous studies have shown that inclusion of arm swing in gait rehabilitation leads to more effective walking recovery in patients with walking impairments. However, little is known about the correct arm-swing trajectories to be used in gait rehabilitation given the fact that changes in walking conditions affect arm swing patterns. In this paper we present a comprehensive look at the effects of a variety of conditions on arm-swing patterns during walking. The results describe the effects of surface slope, walking speed, and physical characteristics on arm swing patterns in healthy individuals. We propose data-driven mathematical models to describe arm-swing trajectories. Thirty individuals (fifteen females and fifteen males) with a wide range of height (1.58-1.91m) and body mass (49-98kg), participated in our study. Based on their self-selected walking speed, each participant performed walking trials with four speeds on five surface slopes while their whole-body kinematics were recorded. Statistical analysis showed that walking speed, surface slope, and height were the major factors influencing arm swing during locomotion. The results demonstrate that data-driven models can successfully describe arm-swing trajectories for normal gait under varying walking conditions. The findings also provide insight into the behavior of the elbow during walking. PMID- 27367785 TI - Catalytic Hairpin Assembly Actuated DNA Nanotweezer for Logic Gate Building and Sensitive Enzyme-Free Biosensing of MicroRNAs. AB - A target-switched DNA nanotweezer is designed for AND logic gate operation and enzyme-free detection of microRNAs (miRNAs) by catalytic hairpin assembly (CHA) and proximity-dependent DNAzyme formation. The double crossover motif-based nanotweezer consists of an arched structure as the set strand for target inputs and two split G-rich DNAs at the termini of two arms for signal output. Upon a CHA, a small amount of binary target inputs can switch numerous open nanotweezers to a closed state, which leads to the formation of proximity-dependent DNAzyme in the presence of hemin to produce a highly sensitive biosensing system. The binary target inputs can be used for successful building of AND logic gate, which is validated by polyacrylamide gel electrophoresis, surface plasmon resonance and the biosensing signal. The developed biosensing system shows a linear response of the output chemiluminescence signal to input binary miRNAs with a detection limit of 30 fM. It can be used for miRNAs analysis in complex sample matrix. This system provides a simple and reusable platform for logic gate operation and enzyme-free, highly sensitive, and specific multianalysis of miRNAs. PMID- 27367786 TI - Semiquantitative dynamic contrast-enhanced MRI for accurate classification of complex adnexal masses. AB - PURPOSE: To identify the best dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) descriptive parameters in predicting malignancy of complex ovarian masses, and develop an optimal decision tree for accurate classification of benign and malignant complex ovarian masses. MATERIALS AND METHODS: Preoperative DCE-MR images of 55 sonographically indeterminate ovarian masses (27 benign and 28 malignant) were analyzed prospectively. Four descriptive parameters of the dynamic curve, namely, time-to-peak (TTP), wash-in-rate (WIR), relative signal intensity (SIrel ), and the initial area under the curve (IAUC60 ) were calculated on the normalized curves of specified regions-of-interest (ROIs). A two-tailed Student's t-test and two automated classifiers, linear discriminant analysis (LDA) and support vector machines (SVMs), were used to compare the performance of the mentioned parameters individually and in combination with each other. RESULTS: TTP (P = 6.15E-8) and WIR (P = 5.65E-5) parameters induced the highest sensitivity (89% for LDA, and 97% for SVM) and specificity (93% for LDA, and 100% for SVM), respectively. Regarding the high sensitivity of TTP and high specificity of WIR and through their combination, an accurate and simple decision tree classifier was designed using the line equation obtained by LDA classification model. The proposed classifier achieved an accuracy of 89% and area under the ROC curve of 93%. CONCLUSION: In this study an accurate decision tree classifier based on a combination of TTP and WIR parameters was proposed, which provides a clinically flexible framework to aid radiologists/clinicians to reach a conclusive preoperative diagnosis and patient-specific therapy plan for distinguishing malignant from benign complex ovarian masses. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:418-427. PMID- 27367787 TI - Treatment of the Immune-Related Adverse Effects of Immune Checkpoint Inhibitors: A Review. AB - Importance: The development of immune checkpoint inhibitors targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death-1 (PD-1) has significantly improved the treatment of a variety of cancers and led to US Food and Drug Administration approvals for patients with a variety of malignant neoplasms. Immune checkpoint inhibitors enhance antitumor immunity by blocking negative regulators of T-cell function that exist both on immune cells and on tumor cells. Although these agents can lead to remarkable responses, their use can also be associated with unique immune-related adverse effects (irAEs). Observations: In general, use of PD-1 inhibitors such as nivolumab and pembrolizumab has a lower incidence of irAEs compared with those that block CTLA 4 such as ipilimumab. The combination of nivolumab and ipilimumab has a higher rate of irAEs than either approach as monotherapy. Consensus guidelines regarding the treatment of the most common irAEs including rash, colitis, hepatitis, endocrinopathies, and pneumonitis have been established. The mainstay of irAE treatment consists of immunosuppression with corticosteroids or other immunosuppressant agents such as infliximab; most irAEs will resolve with appropriate management. Conclusions and Relevance: The clinical use of immune checkpoint inhibitors is expanding rapidly. Oncology practitioners will therefore be required to recognize and manage irAEs in a growing patient population. Early recognition and treatment are essential to prevent patient morbidity and mortality, and adherence to established algorithms is recommended. PMID- 27367788 TI - Outcomes of Children With and Without Hepatic Encephalopathy From the Pediatric Acute Liver Failure Study Group. AB - OBJECTIVES: Hepatic encephalopathy (HE) is challenging to identify in children with acute liver failure and was not a requirement for enrollment into the Pediatric Acute Liver Failure Study Group (PALFSG). The outcomes of PALFSG participants presenting with and without HE are presented. METHODS: PALFSG participants were classified based on daily assessment of HE during the first 7 days following study enrollment: group 1-never developed HE; group 2-no HE at enrollment with subsequent HE development; and group 3-HE at study enrollment. Clinical and biochemical parameters and outcomes of death, spontaneous recovery, or liver transplantation were compared between groups. RESULTS: Data from 769 PALFSG (54% boys; median age 4.2 years; range 0-17.9 years) participants were analyzed, with 277 in group 1 (36%), 83 in group 2 (11%), and 409 in group 3 (53%). Mortality occurred in 11% of all participants and was highest among group 3 participants who demonstrated persistent grade III-IV HE (55%) or showed progression of HE (26%). Eleven (4%) group 1 participants died within 21 days of enrollment. Spontaneous recovery was highest in group 1 (79%) and lowest in group 2 (25%; P < 0.001). CONCLUSIONS: Mortality 21 days after enrollment was highest in participants enrolled with severe HE (grades III or IV) or demonstrating HE progression. Four percent of participants without recorded clinical HE in the 7 days after enrollment, however, died within 21 days. Improved assessment of neurological injury and pediatric acute liver failure prognostication schema are needed. PMID- 27367790 TI - Diabolical Coughing-Prima Facie Protocols for Diagnosis and Treatment of Medically Jaded Patients. PMID- 27367789 TI - Sticky Steroids: In Search of an Approved Treatment for Eosinophilic Esophagitis. PMID- 27367791 TI - Partner Reports of HIV Viral Suppression Predict Sexual Behavior in Serodiscordant Male Couples. PMID- 27367792 TI - Ammonia Borane Dehydrogenation Promoted by a Pincer-Square-Planar Rhodium(I) Monohydride: A Stepwise Hydrogen Transfer from the Substrate to the Catalyst. AB - The pincer d(8)-monohydride complex RhH{xant(P(i)Pr2)2} (xant(P(i)Pr2)2 = 9,9 dimethyl-4,5-bis(diisopropylphosphino)xanthene) promotes the release of 1 equiv of hydrogen from H3BNH3 and H3BNHMe2 with TOF50% values of 3150 and 1725 h(-1), to afford [BH2NH2]n and [BH2NMe2]2 and the tandem ammonia borane dehydrogenation cyclohexene hydrogenation. DFT calculations on the ammonia borane dehydrogenation suggest that the process takes place by means of cis-kappa(2)-PP-species, through four stages including: (i) Shimoi-type coordination of ammonia borane, (ii) homolytic addition of the coordinated H-B bond to afford a five-coordinate dihydride-boryl-rhodium(III) intermediate, (iii) reductive intramolecular proton transfer from the NH3 group to one of the hydride ligands, and (iv) release of H2 from the resulting square-planar hydride dihydrogen rhodium(I) intermediate. PMID- 27367793 TI - Language, gesture, and handedness: Evidence for independent lateralized networks. AB - Language, gesture, and handedness are in most people represented in the left cerebral hemisphere. To explore the relations among these attributes, we collected fMRI images in a large sample of left- and right-handers while they performed language tasks and watched action sequences. Regions of interest included the frontal and parietal areas previously identified as comprising an action-observation network, and the frontal and temporal areas comprising the primary areas for language production and comprehension. All of the language areas and most of the action-observation areas showed an overall left-hemispheric bias, despite the participation of equal numbers of left- and right-handers. A factor analysis of the laterality indices derived from the different areas during the tasks indicated three independent networks, one associated with language, one associated with handedness, and one representing action observation independent of handedness. Areas 44 and 45, which together make up Broca's area, were part of the language and action-observation networks, but were not included in the part of the action observation network that was related to handedness, which in turn was strongly linked to areas in the parietal lobe. These results suggest an evolutionary scenario in which the primate mirror neuron system (MNS) became increasingly lateralized, and later fissioned onto subsystems with one mediating language and the other mediating the execution and observation of manual actions. The second network is further subdivided into one dependent on hand preference and one that is not, providing new insight into the tripartite system of language, handedness, and praxis. PMID- 27367794 TI - Prevention of perceptual-motor decline by branched-chain amino acids, arginine, citrulline after tennis match. AB - Perceptual-motor performance in prolonged tennis matches may be affected by central fatigue. The purpose of this study was to investigate the supplementation of branched-chain amino acids (BCAA), arginine, and citrulline on tennis-specific perceptual-motor performance after a simulated match. Nine male tennis players consumed 0.17 g/kg BCAA, 0.05 g/kg arginine, and 0.05 g/kg citrulline (AA trial), or placebo (PB trial) 1 h before the match. In the perceptual-motor performance test before and after the match, the subjects hit balls to the opposite direction of the examiner's movement. The AA trial showed significantly higher rate of correct direction than the PB trial after the match (AA trial: 93.63 +/- 1.28%, PB trial: 69.09 +/- 2.40%). The AA trial also demonstrated significantly higher post-match accuracy and consistency than the PB trial. The AA trial showed significantly lower heart rate and ratings of perceive exertion during the match, concurrently with a significantly lower plasma total tryptophan/BCAA ratio. Similar post-match plasma NH3 concentrations were found in both trials while the AA trial was significantly higher in NOx concentration. This study suggested that the supplementation could prevent the decline in perceptual-motor performance through alleviation of central fatigue by BCAA and prevention of excess hyperammonemia by arginine and citrulline. PMID- 27367795 TI - Effects of Suboptimally Presented Erotic Pictures on Moral Judgments: A Cross Cultural Comparison. AB - Previous research has identified a set of core factors that influence moral judgments. The present study addresses the interplay between moral judgments and four factors: (a) incidental affects, (b) sociocultural context, (c) type of dilemma, and (d) participant's sex. We asked participants in two different countries (Colombia and Spain) to judge the acceptability of actions in response to personal and impersonal moral dilemmas. Before each dilemma an affective prime (erotic, pleasant or neutral pictures) was presented suboptimally. Our results show that: a) relative to neutral priming, erotic primes increase the acceptance of harm for a greater good (i.e., more utilitarian judgments), b) relative to Colombians, Spanish participants rated causing harm as less acceptable, c) relative to impersonal dilemmas, personal dilemmas reduced the acceptance of harm, and d) relative to men, women were less likely to consider harm acceptable. Our results are congruent with findings showing that sex is a crucial factor in moral cognition, and they extend previous research by showing the interaction between culture and incidental factors in the making of moral judgments. PMID- 27367796 TI - X-Ray Nanoscopy of a Bulk Heterojunction. AB - Optimizing the morphology of bulk heterojunctions is known to significantly improve the photovoltaic performance of organic solar cells, but available quantitative imaging techniques are few and have severe limitations. We demonstrate X-ray ptychographic coherent diffractive imaging applied to all organic blends. Specifically, the phase-separated morphology in bulk heterojunction photoactive layers for organic solar cells, prepared from a 50:50 blend of poly(3-hexylthiophene) (P3HT) and phenyl-C61-butyric acid methyl ester (PCBM) and thermally treated for different annealing times is imaged to high resolution. Moreover, using a fast-scanning calorimetry chip setup, the nano morphological changes caused by repeated thermal annealing applied to the same sample could be monitored. X-ray ptychography resolves to better than 100 nm the phase-segregated domains of electron donor and electron acceptor materials over a large field of view within the active layers. The quantitative phase contrast images further allow us to estimate the local volume fraction of PCBM across the photovoltaically active layers. The volume fraction gradient for different regions provides insight on the PCBM diffusion across the depletion zone surrounding PCBM aggregates. Phase contrast X-ray microscopy is under rapid development, and the results presented here are promising for future studies of organic-organic blends, also under in situ conditions, e.g., for monitoring the structural stability during UV-Vis irradiation. PMID- 27367797 TI - Actor-Partner Interdependence Model Analysis of Sexual Communication and Relationship/Family Planning Factors Among Immigrant Latino Couples in the United States. AB - The Latino population in the United States is quickly growing, and its unintended pregnancy rate is increasing. To decrease unintended pregnancies, couples must mutually agree on family planning. Communication between partners is one key factor identified in successful family planning for couples. Therefore, the purpose of this study was to examine sexual communication and its associations with sexual relationship power, general communication, and views on family planning. The Actor-Partner Interdependence Model was used to analyze dyadic influences of the chosen variables. Forty immigrant Latino couples were recruited from prenatal care clinics. The study results were grouped according to the three types of power structures: exhibition of men's traditional machismo values, exhibition of women's increased power in their relationships, and exhibition of men's and women's own empowerment with sexual communication. There was a negative association between men's views on family planning and women's sexual communication (exhibition of machismo values); a negative association between women's sexual relationship power and their partners' sexual communication (exhibition of women's increased power); and positive associations between men's and women's general communication and sexual communication (exhibition of men's and women's own empowerment). Dyadic influences of sexual communication and associated variables need to be incorporated into interventions to facilitate family planning for couples. PMID- 27367798 TI - Essential Infantile Esotropia: Postoperative Sensory Outcomes of Strabismus Surgery. AB - BACKGROUND: The optimum age for Essential Infantile Esotropia surgery is a controversial subject. Sensory status was evaluated in patients who underwent surgery at different ages in a retrospective study. The setting of the study is the ophthalmology department of a teaching hospital. METHODS: Different clinical characters were analyzed pre- and postoperatively; nine different surgeries were performed. A total of 188 patients presented valid postoperative sensorial data, divided in two groups: surgery at <=2 years (n=69) or >2 years (n=119). Sensory status was dichotomized in binocular single vision (BSV) and exclusion. Univariate differences were assessed with the chi-square test (or Fisher exact test). To identify the independent role of factors associated with the sensory status, all variables showing in univariate analyses a significant association (p<0.05) with the outcome variable were entered into a multivariate logistic regression model. All statistical tests were two-sided. RESULTS: Multivariate analysis confirmed that children operated >2 years were 0.4 times less likely to obtain BSV compared with children operated at <=2 years (AOR. 0.38, 95% C.I. 0.17 0.89, p=0.025). Patients operated on by OO MR rec.+ OO LR res. + OO IO rec.-ap. (intervention type 6) were about 11 times more likely to have BSV than those by OO rec.MR + unilateral res. LR (operation type 2); AOR.: 10.67, 95% C.I.: 1.34 - 85.29, p=0.026). Twenty-nine patients (12.1%) operated at <=2 years of age underwent a reoperation, compared to 33 (8.6%) who underwent surgery after two years (p>0.05). CONCLUSIONS: Our findings suggest to perform EIE surgery between age 1 and 2 and, when indicated, to prefer a six-muscle approach in order to achieve a better sensory function. PMID- 27367799 TI - The Development of Morphological Awareness in Young Bilinguals: Effects of Age and L1 Background. AB - PURPOSE: Current understanding about the effect of first language (L1) background on morphological awareness (MA) development in those who are bilingual is largely limited to school-aged second-language learners. This study examined the development of MA in bilingual Mandarin-English (ManEngBi) and Spanish-English (SpaEngBi) children ages 4 to 7 years, whose L1 is predominated by compounding and derivation, respectively. METHOD: We targeted specific word formation rules that develop within different developmental time frames. Forty-two ManEngBi, 30 SpaEngBi, and 27 English monolingual children divided into 4- to 5-year-old and 6 to 7-year-old age groups produced English words using compounding, the derivational agentive -er suffix, and the derivational characteristic -y suffix for both real and novel word roots. RESULTS: The characteristic -y suffix consistently elicited the poorest performance. This finding held true regardless of language group, age, or novelty of prompts. Both older SpaEngBi and English monolingual children outperformed older ManEngBi children in the characteristic y suffix, whereas the three groups performed comparably on the other two rules at both age intervals. Error analysis further suggested influence of cross linguistic features. CONCLUSIONS: L1 influence on English MA development is sensitive to the developmental time frame of word formation rules. Future studies on the development of MA in bilingual children should adopt a more fine-grained approach and include a wider age range. PMID- 27367801 TI - Stem cells: to be born great, achieve greatness, or have greatness thrust upon them? AB - Induced pluripotent stem cells (iPSCs) have opened new doors in providing an ethical, patient-specific cell source towards tissue engineering. Developing these therapies involves the production of reprogrammed iPSCs, expanding them while maintaining pluripotency, then differentiating them into functional tissues. To bring these therapies to the clinic, efficient and GMP-compliant manufacturing methods are required. In this Research Highlight, we describe recent innovations to several aspects of the pluripotent cell therapy pipeline. PMID- 27367800 TI - The Current Recommended Vitamin D Intake Guideline for Diet and Supplements During Pregnancy Is Not Adequate to Achieve Vitamin D Sufficiency for Most Pregnant Women. AB - BACKGROUND: The aims of this study were to determine if pregnant women consumed the recommended vitamin D through diet alone or through diet and supplements, and if they achieved the current reference range vitamin D status when their reported dietary intake met the current recommendations. METHODS: Data and banked blood samples collected in second trimester from a subset of 537 women in the APrON (Alberta Pregnant Outcomes and Nutrition) study cohort were examined. Frozen collected plasma were assayed using LC-MS/MS (liquid chromatography-tandem mass spectrometry) to determine 25(OH)D2, 25(OH)D3, 3-epi-25(OH)D3 concentrations. Dietary data were obtained from questionnaires including a Supplement Intake Questionnaire and a 24-hour recall of the previous day's diet. RESULTS: Participants were 87% Caucasian; mean (SD) age of 31.3 (4.3); BMI 25.8 (4.7); 58% were primiparous; 90% had education beyond high school; 80% had a family income higher than CAN $70,000/year. 25(OH)D2, 25(OH)D3, and 3-epi-25(OH)D3) were identified in all of the 537 plasma samples;3-epi-25(OH)D3 contributed 5% of the total vitamin D. The median (IQR) total 25(OH)D (D2+D3) was 92.7 (30.4) nmol/L and 20% of women had 25(OH)D concentration < 75 nmol/L. The median (IQR) reported vitamin D intake from diet and supplements was 600 (472) IU/day. There was a significant relationship between maternal reported dietary vitamin D intake (diet and supplement) and 25(OH)D and 3-epi-25(OH)D3 concentrations in an adjusted linear regression model. CONCLUSIONS: We demonstrated the current RDA (600 IU/ day) may not be adequate to achieve vitamin D status >75 nmol/L in some pregnant women who are residing in higher latitudes (Calgary, 51 degrees N) in Alberta, Canada and the current vitamin D recommendations for Canadian pregnant women need to be re-evaluated. PMID- 27367802 TI - Controlling the Reversible Assembly of Liposomes through a Multistimuli Responsive Anchored DNA. AB - We present a novel approach to reversibly control the assembly of liposomes through an anchored multistimuli responsive DNA oligonucleotide decorated with an azobenzene moiety (AZO-ON1). We show that liposomes assembly can be simultaneously controlled by three external stimuli: light, Mg(2+), and temperature. (i) Light alters the interaction of AZO-ON1 with liposomes, which influences DNA coating and consequently liposomes assembly. (ii) Mg(2+) induces the assembly, hence variation in its concentration enables for reversibility. (iii) Double-stranded AZO-ON1 is more efficient than single-stranded AZO-ON1 in triggering the assembly of liposomes and temperature has been used for controllable assembly through DNA thermal denaturation. Our multiresponsive AZO ON1 represents a unique example in which multiple stimuli can be simultaneously applied to regulate the reversible assembly of liposomes. PMID- 27367804 TI - Severe Intrapartum Asphyxia from Subamniotic Hemorrhage. AB - Subamniotic hemorrhage results from rupture of chorionic vessels near the cord insertion. In the literature, it has never been a major cause for severe intrapartum complications. We report the first case of acute massive subamniotic hemorrhage intrapartum resulting in severe perinatal asphyxia. PMID- 27367803 TI - Small Incision Lenticule Extraction (SMILE) versus Femtosecond Laser-Assisted In Situ Keratomileusis (FS-LASIK) for Myopia: A Systematic Review and Meta-Analysis. AB - PURPOSE: The goal of this study was to compare small incision lenticule extraction (SMILE) with femtosecond laser-assisted in situ keratomileusis (FS LASIK) for treating myopia. METHODS: The CENTRAL, EMBASE, PubMed databases and a Chinese database (SinoMed) were searched in May of 2016. Twelve studies with 1,076 eyes, which included three randomized controlled trials (RCTs) and nine cohorts, met our inclusion criteria. The overall quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group framework. Data were extracted and analysed at three to six months postoperatively. Primary outcome measures included a loss of one or more lines of best spectacle corrected visual acuity (BSCVA), uncorrected visual acuity (UCVA) of 20/20 or better, mean logMAR UCVA, postoperative mean spherical equivalent (SE) and postoperative refraction within +/-1.0 D of the target refraction. Secondary outcome measures included ocular surface disease index (OSDI), tear breakup time (TBUT) and Schirmer's 1 test (S1T) as dry eye parameters, along with corneal sensitivity. RESULTS: The overall quality of evidence was considered to be low to very low. Pooled results revealed no significant differences between the two groups with regard to a loss of one or more lines in the BSCVA (OR 1.71; 95% CI: 0.81, 3.63; P = 0.16), UCVA of 20/20 or better (OR 0.71; 95% CI: 0.44, 1.15; P = 0.16), logMAR UCVA (MD 0.00; 95% CI: 0.03, 0.04; P = 0.87), postoperative refractive SE (MD -0.00; 95% CI: -0.05, 0.05; P = 0.97) or postoperative refraction within +/-1.0 D of the target refraction (OR 0.78; 95% CI: 0.22, 2.77; P = 0.70) within six months postoperatively. The pooled analysis also indicated that the FS-LASIK group suffered more severely from dry eye symptoms (OSDI; MD -6.68; 95% CI: -11.76, 2.00; P = 0.006) and lower corneal sensitivity (MD 12.40; 95% CI: 10.23, 14.56; P < 0.00001) at six months postoperatively. CONCLUSIONS: In conclusion, both FS LASIK and SMILE are safe, effective and predictable surgical options for treating myopia. However, dry eye symptoms and loss of corneal sensitivity may occur less frequently after SMILE than after FS-LASIK. PMID- 27367805 TI - Free-Flap Reconstruction: What Do Microsurgeons Prefer for Themselves? AB - Background The recent development of perforator flaps has changed the reconstructive strategy for common integumental defects and has refocused the attention of microsurgeons to donor site morbidity. We asked a representative panel of microsurgeons about the free flap they would use to cover a common integumental defect on their own body to investigate the best free-flap donor sites. Methods In total, 100 practitioners participated in the "FreeFlap4U" study, representing 77.3% of the French national plastic surgery teams practicing microsurgery. To assess changing attitudes, we also compared microsurgeons below 40 years of age (called junior microsurgeons, JMs) with those above 40 years of age (called senior microsurgeons, SMs). Results Perforator flaps were preferred for the first line (JMs) and second line (JMs and SMs) of treatment compared with other flaps. JMs emphasized lower donor site morbidity, whereas SMs favored reliability (p = 0.013) and considered perforator flaps as a second-line treatment. Radial forearm and transverse rectus abdominis flaps were largely dismissed due to high morbidity. Some microsurgeons were influenced by the potential secondary benefit of the integument sample at the donor site. Conclusions Microsurgeons interviewed clearly moved toward perforator flaps, such as the anterolateral thigh, thoracodorsal artery perforator, and superficial circumflex iliac artery types, to cover common integumental defects. In the coming years, we believe that this choice, emitted by the microsurgeons for themselves, will be applied extensively by these surgeons for their patients. PMID- 27367806 TI - Do Skin Perforator Flaps Accommodate Foot Growth in Children after Reconstruction? AB - Backgrounds Whether or not the flap accommodates growth is unpredictable and remains to be determined. We hypothesized that perforator flaps may accommodate growth after reconstruction in children and evaluated change of the flap after foot and ankle reconstruction. Methods A retrospective review of 28 children from 2003 to 2015 was performed with children under 14 years of age who had foot and ankle soft tissue defects. The following evaluations were made: (1) comparing flap to foot growth, (2) comparing flap/foot dimension using the photo anthropometric technique defined as proportionality index (PI), and (3) comparing PI ratio of flap to foot area at intervals (DeltaPI). All values were measured and statistically evaluated by Pearson's correlation analysis and paired t-test. Subsequent complications and functional results were also evaluated. Result Foot and flap after growth had positive correlation in Pearson's correlation analysis, showing the flap expands as the foot grows. The mean intraoperative and postoperative PI was 0.3 and 0.2475, respectively, with statistical significance (DeltaPI; p < 0.01). However, no patient had growth disturbance or functional impairment. There was no correlation between DeltaPI and motor power grade or between DeltaPI and range of motion (p > 0.01). Conclusion The skin perforator flap significantly expands during growth after reconstruction. Although the expansion of the flap to foot may not be a one-to-one ratio, it expands enough not to impair the growth or functional outcome of the foot. Skin perforator flap showed growth as children grow and can be considered as a reliable and feasible option in pediatric reconstructive surgery. PMID- 27367807 TI - The Effect of Inducible Nitric Oxide Synthase on Multiterritory Perforator Flap Survival in Rats. AB - Background Inducible nitric oxide synthase (iNOS) plays an important role in vasodilation, angiogenesis, and ischemia-reperfusion injury. We investigated the effects of iNOS on the survival and choke vessels of multiterritory perforator flaps in rats. Methods In this study, 84 rats were divided into two groups of 42 rats each and subjected to multiterritory perforator flap operations. Rats in group A received daily intraperitoneal doses of 100 mg per kg of aminoguanidine (AG) and rats in group B received daily intraperitoneal injections of the same volume of saline solution. On postoperative day 7, the surviving flap area was calculated as a percentage of the total flap dimensions using DP2-BSW software. The diameter and density of microvessels in the second choke zone of the flap were calculated from histology studies. The nitric oxide (NO) content was measured using NO concentration assay kits, and the levels of vascular endothelial growth factor (VEGF) and iNOS were assessed using western blotting. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured using test kits. Laser Doppler imaging was used to evaluate flap perfusion in the second choke zone for 7 days after surgery. Results The flap survival area, diameter and density of microvessels, iNOS and VEGF levels, NO content, blood perfusion, and MDA content were significantly higher in the control group compared with the AG group, whereas SOD activity was significantly lower in the control group. Conclusions iNOS has a beneficial effect on the survival of multiterritory perforator flaps. PMID- 27367808 TI - Ex Vivo Delay: A Novel Approach to Increase Prefabricated Flaps Survival Rate. AB - Background Limited flap survival area is the main disadvantage of prefabricated flaps. To deal with this problem, surgical delay is the common method to achieve a better prognosis. This method requires multiple surgeries with the known associated burdens. We have developed a new strategy, ex vivo delay, utilizing the pathophysiology of surgical delay while avoiding the need for multiple surgeries. Methods We created a rodent animal model utilizing a two-stage operation of a prefabricated abdominal flap. The rats were randomly divided into three groups (n = 6 per group): group A, the control group (no intervention), group B, delayed by the ex-vivo delay device, and group C, delayed using surgical delay technique. Data were collected according to macroscopic analysis, near infrared fluorescence imaging, and capillary densities. Results According to the macroscopic analysis, groups B and C had a significantly larger flap survival area compared with group A, but group B had a significantly smaller survival area than group C. The near-infrared fluorescence imaging showed the perfusion areas of group B and C to be larger than that of group A. Histologically, groups B and C had a significantly higher capillary density than group A. The vessel caliber in group C was larger than that of groups A and B. Conclusions The ex vivo delay strategy successfully increased flap survival area. This strategy worked by establishing ischemia and enhancing neovascularization. Further improvements in the surgical technique could produce outcomes similar to those seen with surgical delay. PMID- 27367809 TI - Steps Toward Creating A Therapeutic Community for Inpatients Suffering from Chronic Ulcers: Lessons from Allada Buruli Ulcer Treatment Hospital in Benin. AB - BACKGROUND: Reducing social distance between hospital staff and patients and establishing clear lines of communication is a major challenge when providing in patient care for people afflicted by Buruli ulcer (BU) and chronic ulcers. Research on hospitals as therapeutic communities is virtually non-existent in Africa and is currently being called for by medical anthropologists working in the field of health service and policy planning. This paper describes a pioneering attempt to establish a therapeutic community for patients suffering from BU and other chronic ulcers requiring long term hospital care in Benin. METHODS: A six-month pilot project was undertaken with the objectives of establishing a therapeutic community and evaluating its impact on practitioner and patient relations. The project was designed and implemented by a team of social scientists working in concert with the current and previous director of a hospital serving patients suffering from advanced stage BU and other chronic ulcers. Qualitative research initially investigated patients' understanding of their illness and its treatment, identified questions patients had about their hospitalization, and ascertained their level of social support. Newly designed question-answer health education sessions were developed. Following these hospital wide education sessions, open forums were held each week to provide an opportunity for patients and hospital staff to express concerns and render sources of discontent transparent. Patient group representatives then met with hospital staff to problem solve issues in a non-confrontational manner. Psychosocial support for individual patients was provided in a second intervention which took the form of drop-in counseling sessions with social scientists trained to serve as therapy facilitators and culture brokers. RESULTS: Interviews with patients revealed that most patients had very little information about the identity of their illness and the duration of their treatment. This knowledge gap surprised clinic staff members, who assumed someone had provided this information. Individual counseling and weekly education sessions corrected this information gap and reduced patient concerns about their treatment and the status of their healing process. This led to positive changes in staff-patient interactions. There was widespread consensus among both patients and staff that the quality of communication had increased significantly. Open forums providing an opportunity for patients and staff to air grievances were likewise popular and patient representative meetings resulted in productive problem solving supported by the hospital administration. Some systemic problems, however, remained persistent challenges. Patients with ulcers unrelated to BU questioned why BU patients were receiving preferential treatment, given special medicines, and charged less for their care. The idea of subsidized treatment for one disease and not another was hard to justify, especially given that BU is not contagious. CONCLUSION: This pilot project illustrates the basic principles necessary for transforming long term residential hospitals into therapeutic communities. Although the focus of this case study was patients suffering from chronic ulcers, the model presented is relevant for other types of patients with cultural adaptation. PMID- 27367810 TI - Vitamin D Status and Long-Term Mortality in Community-Acquired Pneumonia: Secondary Data Analysis from a Prospective Cohort. AB - BACKGROUND: Low vitamin D status has been associated with short-term (30-day) mortality in hospitalized adults with community-acquired pneumonia (CAP). Data on its prevalence in these patients are scarce, and impact on long-term prognosis is unknown. We examined the prevalence of vitamin D deficiency and inadequacy and their effect on long-term mortality in hospitalized adults with CAP. METHODS: Secondary follow-up analysis of data from a prospectively recruited (January 2008 January 2011) well-defined cohort of 241 hospital survivors of CAP (Norway, latitude 60 degrees N). Serum 25-hydroxyvitamin D levels, demographic, clinical, and laboratory data were measured within 48 hours of admission. The etiology of CAP was established in 63% of patients through extensive microbiological investigations. Mortality data were obtained from the national Cause of Death Registry. Explanatory strategy and Cox regression models were used to explore the association between vitamin D status and all-cause mortality. RESULTS: Median age was 66 years. Eighty-seven (36%) patients were vitamin D deficient (<30 nmol/L), 81 (34%) were inadequate (30-49 nmol/L), and 73 (30%) were sufficient (>=50 nmol/L). Seventy-two patients died over a median of 1839 days (range 1-2520 days), corresponding to cumulative 5-year survival rates of 66.2% (95% CI 56.2 76.2%), 77.0% (67.6-86.4%), and 77.8% (67.8-87.8%) for vitamin D deficient, inadequate, and sufficient patients, respectively. After adjusting for confounders (age, chronic obstructive pulmonary disease, immunocompromization and season), vitamin D deficiency, but not inadequacy, was significantly associated with higher mortality compared to patients with sufficiency (HR 1.91, 95% CI 1.06 3.45; P = .031). CONCLUSIONS: There is a high prevalence of vitamin D deficiency and inadequacy among hospitalized adults with CAP. The results of this study also suggest that vitamin D deficiency is associated with an increased risk of mortality way beyond the short-term in these patients. PMID- 27367811 TI - Performance of rotary kiln reactor for the elephant grass pyrolysis. AB - The influence of process conditions (rotary speed/temperature) on the performance of a rotary kiln reactor for non-catalytic pyrolysis of a perennial grass (elephant grass) was investigated. The product yields, the production of non condensable gases as well as the biochar properties were evaluated. The maximum H2 yield was close to that observed for catalytic pyrolysis processes, while the bio-oil yield was higher than reported for pyrolysis of other biomass in rotary kiln reactors. A H2/CO ratio suitable for Fischer-Tropsch synthesis (FTS) was obtained. The biochars presented an alkaline pH (above 10) and interesting contents of nutrients, as well as low electrical conductivity, indicating a high potential as soil amendment. PMID- 27367812 TI - Strategy study on enhancing lipid productivity of filamentous oleaginous microalgae Tribonema. AB - Filamentous microalgae Tribonema is promising for biodiesel production in terms of high lipid content, easy harvesting and good contamination tolerance. As high lipid productivity is a key basis, several methods including different culture medium, phosphorus, iron and CO2 inductions were tested to enhance lipid productivity in Tribonema minus. T. minus subjected to BG11-freshwater medium achieved a favorable lipid productivity of 216.18mgL(-1)d(-1), much higher than those in other culture medium (BG11-S, Kuhl, f/2, f, 2f, BBM, ASW and ES). Secondly, the optimal phosphorus, iron and CO2 concentrations for high lipid productivity of T. minus were obtained, respectively. Finally, the cells of T. minus grown in optimized BG11 medium containing 80mgL(-1) KH2PO4 and 6mgL(-1) FeC6H5O7.NH4OH with 2% CO2 achieved a lipid productivity of 384.67mgL(-1)d(-1), representing a 1.56-fold increase from the control. Therefore, the strategy to enhance lipid productivity of T. minus was successfully proposed. PMID- 27367813 TI - Butanol production from lignocellulose by simultaneous fermentation, saccharification, and pervaporation or vacuum evaporation. AB - Techno-economic study of acetone, butanol and ethanol (ABE) fermentation from lignocellulose was performed. Simultaneous saccharification, fermentation and vacuum evaporation (SFS-V) or pervaporation (SFS-P) were proposed. A kinetic model of metabolic pathways for ABE fermentation with the effect of phenolics and furans in the growth was proposed based on published laboratory results. The processes were optimized in Matlab(r). The end ABE purification was carried out by heat-integrated distillation. The objective function of the minimization was the total annualized cost (TAC). Fuel consumption of SFS-P using poly[1 (trimethylsilyl)-1-propyne] membrane was between 13.8 and 19.6% lower than SFS-V. Recovery of furans and phenolics for the hybrid reactors was difficult for its high boiling point. TAC of SFS-P was increased 1.9 times with supplementation of phenolics and furans to 3g/l each one for its high toxicity. Therefore, an additional detoxification method or an efficient pretreatment process will be necessary. PMID- 27367814 TI - Hydrothermal carbonization of sewage sludge: The effect of feed-water pH on fate and risk of heavy metals in hydrochars. AB - In this study, the effect of feed-water pH (pH=2-12) on fate and risk of heavy metals (HMs) in hydrochars (HCs) was investigated. Hydrothermal carbonization (HTC) of sewage sludge (SS) was carried out with different feed-water pH at 270 degrees C. The research results showed that changing feed-water pH had a positive effect on accumulating Pb, Ni, Cd and Zn in HCs. Chemical forms of Cu and Cr converted from an unstable state to stable in the alkaline environment while in the acidic condition was opposite. The effect of feed-water pH on the chemical forms of HMs was variable but not significant. Risk assessments of Igeo, Er(i), RAC and RI were applied to evaluate the accumulation levels of individual metal, the potential ecological risks, the bio-availabilities and the comprehensive toxicity and sensitivity of HMs, respectively. The lowest pollution level of HMs was obtained at 270 degrees C with pH=11. PMID- 27367815 TI - Microbial community and metabolism activity in a bioelectrochemical denitrification system under long-term presence of p-nitrophenol. AB - Bioelectrochemical denitrification system (BEDS) is a promising technology for nitrate removal from wastewaters. The hazards and effects concerning p nitrophenol (PNP) towards BEDS lack enough investigations and possess great research prospects. This study investigated how PNP affected the nitrate removal efficiency, microbial communities, functional denitrifying genes abundances, nitrate and nitrite reductase activities, diffusible signal factors (DSF) release, and extracellular polymeric substances (EPS) production in the BEDS. Results indicated that nitrate removal efficiency decreased with initial PNP concentration increased from 0 to 100mg/L. Phylum Firmicutes and class Clostridia were the main contributors for denitrification process in this BEDS. The abundances of the denitrifying genes nirS, nirK, napA, and narG all presented decreased trends with increasing PNP. In addition, the concentrations of nitrate reductase (NR), nitrite reductase (NIR), and EPS obviously decreased, while the concentration of DSF increased with increasing PNP, which demonstrated that higher PNP would inhibit the biofilm formation. PMID- 27367816 TI - Reevaluation of the global warming impacts of algae-derived biofuels to account for possible contributions of nitrous oxide. AB - The environmental impacts of algae biofuels have been evaluated by life-cycle assessment (LCA); however, these analyses have overlooked nitrous oxide (N2O), a potent greenhouse gas. A literature analysis was performed to estimate algal N2O emissions and assess the impacts of growth conditions on flux magnitudes. Nitrogen source and dissolved oxygen concentration were identified as possible key contributors; therefore, their individual and combined impacts were evaluated using bench-scale experiments. It was observed that maximum N2O emissions (77.5MUg/galgae/day) occur under anoxic conditions with nitrite. Conversely, minimum emissions (6.25MUg/galgae/day) occur under oxic conditions with nitrate. Aggregated N2O flux estimates were then incorporated into a LCA framework for algae biodiesel. Accounting for "low" N2O emissions mediated no significant increase (<1%) compared to existing GWP estimates; however, "high" N2O emissions mediate an increase of roughly 25%, potentially jeopardizing the anticipated economic and environmental performances of algae biofuels. PMID- 27367817 TI - Small molecule hydration energy and entropy from 3D-RISM. AB - Implicit solvent models offer an attractive way to estimate the effects of a solvent environment on the properties of small or large solutes without the complications of explicit simulations. One common test of accuracy is to compute the free energy of transfer from gas to liquid for a variety of small molecules, since many of these values have been measured. Studies of the temperature dependence of these values (i.e. solvation enthalpies and entropies) can provide additional insights into the performance of implicit solvent models. Here, we show how to compute temperature derivatives of hydration free energies for the 3D RISM integral equation approach. We have computed hydration free energies of 1123 small drug-like molecules (both neutral and charged). Temperature derivatives were also used to calculate hydration energies and entropies of 74 of these molecules (both neutral and charged) for which experimental data is available. While direct results have rather poor agreement with experiment, we have found that several previously proposed linear hydration free energy correction schemes give good agreement with experiment. These corrections also provide good agreement for hydration energies and entropies though simple extensions are required in some cases. PMID- 27367819 TI - To Appear in CHEMICAL REVIEWS, Vol. 99, No. 8, or in a later issue. PMID- 27367818 TI - Effect of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on Conduction System Disease. AB - IMPORTANCE: Cardiac conduction abnormalities are associated with an increased risk for morbidity and mortality, and understanding factors that accelerate or delay conduction system disease could help to identify preventive and therapeutic strategies. Antifibrotic and anti-inflammatory properties of angiotensin converting enzyme inhibitors and treatment for hyperlipidemia may reduce the risk for incident conduction system disease. OBJECTIVE: To identify the effect of pharmacologic therapy randomization and clinical risk factors on the incidence of conduction system disease. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) investigation acquired data from 623 North American centers. A total of 21 004 ambulatory individuals 55 years or older with hypertension and at least 1 other cardiac risk factor were included in the analysis. INTERVENTIONS: Participants were randomly assigned to receive amlodipine besylate, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin sodium vs usual care. MAIN OUTCOMES AND MEASURES: An electrocardiogram (ECG) was obtained at study enrollment and every 2 years of follow-up. The development of incident first-degree atrioventricular block, left anterior fascicular block, incomplete left bundle branch block (LBBB), LBBB, incomplete right bundle branch block (RBBB), RBBB, or intraventricular conduction delay was assessed by serial ECGs. RESULTS: The 21 004 participants (11 758 men [56.0%]; 9246 women [44.0%]; mean [SD] age, 66.5 [7.3] years) underwent a mean (SD) follow-up of 5.0 (1.2) years. Among the 1114 participants who developed any conduction defect, 389 developed LBBB, 570 developed RBBB, and 155 developed intraventricular conduction delay. Compared with chlorthalidone, randomization to lisinopril was associated with a significant 19% reduction in conduction abnormalities (hazard ratio [HR], 0.81; 95% CI, 0.69-0.95; P = .01). Treatment with amlodipine, however, was not associated with a significant difference in conduction outcome events (HR, 0.94; 95% CI, 0.81-1.09; P = .42). Similarly, pravastatin treatment was not associated with a reduced adjusted risk for incident disease compared with usual hyperlipidemia treatment (HR, 1.13; 95% CI, 0.95-1.35; P = .18). Increased age (HR, 1.47; 95% CI, 1.34-1.63; P < .001), male sex (HR, 0.59; 95% CI, 0.50-0.73; P < .001), white race (HR, 0.59; 95% CI, 0.50 0.70; P < .001), diabetes (HR, 1.23; 95% CI, 1.07-1.42; P = .003), and left ventricular hypertrophy (HR, 3.20; 95% CI, 2.61-3.94; P < .001) were also independently associated with increased risk for conduction system disease. CONCLUSIONS AND RELEVANCE: Incident conduction system disease is significantly reduced by lisinopril therapy and is independently associated with multiple clinical factors. Further studies are warranted to determine whether pharmacologic treatment affects conduction abnormality outcomes, including pacemaker implantation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000542. PMID- 27367820 TI - Iron-Catalyzed Diastereoselective Synthesis of Unnatural Chiral Amino Acid Derivatives. AB - An iron-catalyzed diastereoselective synthesis of unnatural chiral (S)-alpha amino acids with gamma-quaternary carbon centers has been developed. The protocol uses inexpensive iron salt as the catalyst, readily available 2-phthaloyl acrylamide and alkenes as the starting materials, and phenylsilane as the reductant, and the reactions were performed well in mixed solvent of 1,2 dichloroethane and ethylene glycol at room temperature. The method shows some advantages including simple and wide substrates, mild conditions, high diastereoselectivity, and easy workup procedures. PMID- 27367821 TI - A randomized trial comparing two interventions to increase physical activity among patients undergoing bariatric surgery. AB - OBJECTIVE: To test the effectiveness of two levels of physical activity interventions before and up to 61/2 months after bariatric surgery. METHODS: Before surgery, individuals completed submaximal exercise testing on a treadmill. After random assignment to standard care, pedometer use, or exercise counseling plus pedometer, participants wore an accelerometer for approximately 2 weeks and returned it to the bariatric center before surgery and 2, 4, and 6 months postoperatively. RESULTS: Individuals in exercise counseling plus pedometer had higher steps per day and bout minutes of exercise per week than standard care and pedometer use over the course of the study. There were no group differences related to exercise tolerance; however, all groups made significant improvement. There was no statistically significant change in sedentary or light activity nor was there a difference between groups. CONCLUSIONS: Exercise counseling using pedometers increases physical activity from the perioperative period to 61/2 months after surgery, but providing pedometers without professional feedback may not be more effective than standard bariatric surgery treatments. Rapid weight loss increases exercise tolerance and may mask the fitness improvements achieved through a modest physical activity intervention during the first 6 months after bariatric surgery. PMID- 27367822 TI - Association between physical function and the load pattern during stepping-up motion in community-dwelling elderly women. AB - OBJECTIVE: Stepping-up motion is challenging task for elderly people in daily life. The present study investigated the relationship between the load pattern during stepping-up motion at maximum speed and physical function in elderly women. METHODS: The subjects comprised 109 community-dwelling elderly women (age 72.5+/-5.3years). The load pattern (maximum load, rate of load production, and stepping-up time) during ascending a 30cm step at maximum speed was measured, using a step up platform that measures the load at the lower and upper level. Physical function, including hip and knee extensor strength and performance on the vertical jump test, one-legged stance test, timed "Up & Go" (TUG) test, and stepping test were measured. RESULTS: Pearson's correlation analysis showed that stepping-up time was correlated with the maximum load at the lower level (r= 0.51), but not with the maximum load at the upper level. A multiple regression analysis showed that hip extensor strength and performance on the vertical jump, TUG, and stepping tests were significant determinants of the load pattern during stepping-up motion in the elderly women. CONCLUSIONS: Our study revealed that rapid stepping-up ability was more closely related to the maximum load during push-off at the lower level rather than that during weight loading on the upper level, and that the load pattern during stepping-up motion in elderly women was associated with various physical functions such as the hip extensor strength, leg muscle power, dynamic balance function, and agility. PMID- 27367823 TI - DRD4, Income, and Children's Food Choices: Plasticity Allele or Different Opportunities? PMID- 27367824 TI - Cytokine-mediated blood brain barrier disruption as a conduit for cancer/chemotherapy-associated neurotoxicity and cognitive dysfunction. AB - Neurotoxicity is a common side effect of chemotherapy treatment, with unclear molecular mechanisms. Clinical studies suggest that the most frequent neurotoxic adverse events affect memory and learning, attention, concentration, processing speeds and executive function. Emerging preclinical research points toward direct cellular toxicity and induction of neuroinflammation as key drivers of neurotoxicity and subsequent cognitive impairment. Emerging data now show detectable levels of some chemotherapeutic agents within the CNS, indicating potential disruption of blood brain barrier integrity or transport mechanisms. Blood brain barrier disruption is a key aspect of many neurocognitive disorders, particularly those characterized by a proinflammatory state. Importantly, many proinflammatory mediators able to modulate the blood brain barrier are generated by tissues and organs that are targets for chemotherapy-associated toxicities. This review therefore aims to explore the hypothesis that peripherally derived inflammatory cytokines disrupt blood brain barrier permeability, thereby increasing direct access of chemotherapeutic agents into the CNS to facilitate neuroinflammation and central neurotoxicity. PMID- 27367825 TI - Programmatic experience of post-partum IUD use in Zambia: an observational study on continuation and satisfaction. AB - OBJECTIVES: The aim of the study was to assess continuation rates and satisfaction among post-partum intrauterine device (PPIUD) accepters. METHODS: This prospective observational study comprised 591 Zambian women who underwent PPIUD insertion at sites of the Society for Family Health, Lusaka, Zambia. The women were contacted 6-12 months after PPIUD insertion and asked to return to the clinic for interview and examination. If the IUD strings were not visible, an ultrasound was performed. Participants were asked about their satisfaction with the PPIUD. Main outcome measures were short-term PPIUD continuation and reported complications according to time of insertion. RESULTS: Of 591 women enrolled, 305 women attended the follow-up appointment for interview and examination, giving a power of 80% to estimate an expulsion rate of 10 +/- 5%. The IUD was inserted within 10 min of placental delivery (post-placental insertion) in 24.3% of participants (n = 74) and within 48 h (immediate post-partum insertion) in 71.1% of participants (n = 217). The total expulsion rate was 5.6%. Expulsion rates for post-placental and immediate post-partum insertions were 10.8% and 4.1%, respectively. No significant difference in expulsion rates was found (p = 0.10). Of those with an expulsion, 76.5% (n = 13) recognised that it had occurred. There were no reported complications, and 94.1% of women reported being satisfied or very satisfied with their PPIUD (n = 287). CONCLUSIONS: Overall, expulsion rates were lower than previously reported, particularly for immediate post-partum insertions. Attention to high fundal placement at insertion is a likely explanation for the low expulsion rates. Contrary to conventional wisdom, these low expulsion rates indicate that previous notions regarding insertion timing may not be accurate. Satisfaction levels were also favourable. PPIUD can be safe, acceptable and feasible in an African setting. PMID- 27367826 TI - High-Risk Patients in the Evolving Landscape of Carotid Revascularization. PMID- 27367827 TI - Seawater temperature effect on metal accumulation and toxicity in the subantarctic Macquarie Island isopod, Exosphaeroma gigas. AB - Very little is currently known of subantarctic nearshore invertebrates' sensitivity to environmental metals and the role of temperature in this relationship. This study investigated Cu and Zn toxicity in the common subantarctic intertidal isopod, Exosphaeroma gigas, and the influence of temperature on Cu toxicity and bioaccumulation kinetics. Adult E. gigas are insensitive to Cu and Zn at concentrations of 3200 and 7400MUg/L respectively in non-renewal tests at 5.5 degrees C (ambient subtidal temperature) over 14days. Under renewed exposures over the same temperature and time period the LC50 for copper was 2204MUg/L. A 10-fold increase in Cu body burden occurred relative to zinc, indicating E. gigas has different strategies for regulating the two metals. Copper toxicity and time to mortality both increased with elevated temperature. However, temperature did not significantly affect Cu uptake rate and efflux rate constants derived from biodynamic modelling at lower Cu concentrations. These results may be attributable to E. gigas being an intertidal species with physiological mechanisms adapted to fluctuating environmental conditions. Cu concentrations required to elicit a toxicity response indicates that E. gigas would not be directly threatened by current levels of Cu or Zn present in Macquarie Island intertidal habitats, with the associated elevated temperature fluctuations. This study provides evidence that the sensitivity of this subantarctic intertidal species to metal contaminants is not as high as expected, and which has significance for the derivation of relevant guidelines specific to this distinct subpolar region of the world. PMID- 27367828 TI - Interactions of waterborne and dietborne Pb in rainbow trout, Oncorhynchus mykiss: Bioaccumulation, physiological responses, and chronic toxicity. AB - In Pb-contaminated environments, simultaneous exposure to both waterborne and dietborne Pb is likely to occur. This study examined the potential interactive effects of these two pathways in juvenile rainbow trout that were exposed to Pb in the water alone, in the diet alone, and in combination for 7 weeks. The highest waterborne Pb concentration tested (110MUgL(-1)) was approximately equivalent to the 7-week LC20 (97MUgL(-1)) measured in a separate trial, while the lowest was a concentration often measured in contaminated environments (8.5MUgL(-1)). The live diet (10% daily ration on a wet mass basis) consisted of oligochaete worms (Lumbriculus variegatus) pre-exposed for 28days to the same waterborne Pb concentration, and the highest dietary dosing rate to the trout was 12.6MUg Pb g fish(-1)day(-1). With waterborne exposure, whole body Pb burden increased to a greater extent in the worms than in the fish. Nonetheless, in trout waterborne exposure still resulted in 20-60-fold greater Pb accumulation compared to dietborne Pb exposure. However, combined exposure to both waterborne and dietborne Pb reduced the whole body accumulation extensively at waterborne Pb>50MUgL(-1), with similar antagonistic interaction in liver and carcass (but not gill or gut) at a lower threshold of 20MUgL(-1). Growth effects in trout were minimal with marginal reductions in the dietborne and combined exposures seen only at 110MUgL(-1). Chronic Pb exposure reduced lipid and carbohydrates level in the worms by 50% and 80% respectively, while protein was unchanged, so growth effects in trout may have been of indirect origin. After 7 weeks, Ca(2+) homeostasis in the trout was unaffected, but there were impacts on Na(+). Blood Na(+) was reduced in waterborne and dietborne exposures, while gut Na(+)/K(+) ATPase activities were reduced in waterborne and combined exposures. This study is the first, to our knowledge to examine the interaction of waterborne and dietborne Pb exposure in fish. While physiological impacts of Pb were observed in both worms and fish, higher concentrations of dietborne Pb actually protected fish from waterborne Pb bioaccumulation and these effects. The impacts of metals on diet quality should not be neglected in future dietborne toxicity studies using live prey. PMID- 27367829 TI - Abnormal expression of TLRs may play a role in lower embryo quality of women with polycystic ovary syndrome. AB - Toll-like receptors (TLRs) localize in mammalian ovary, including granulosa cells, cumulus cells, and theca cells. Previous studies demonstrated that TLRs may be important for the cumulus-oocyte complex expansion and fertilization. There is no evidence to indicate that the deletion of TLRs will induce infertility; however, the abnormal expression of TLRs may decrease oocyte quality and fertility rate. In the present study, we investigated the effects of polycystic ovary syndrome (PCOS) on the expression of TLRs in cumulus cells by using western-blot and quantitative real-time PCR (qRT-PCR) analyses. We found that the expression of TLR4 and 9 in cumulus cells was influenced significantly by PCOS. We also observed that overweight/obesity changed the expression of TLR2 and 5 in cumulus cells of PCOS subjects. In addition, we found that the rate of available embryos of women with PCOS was slightly lower. These results indicate that the abnormal expression of TLRs in cumulus may be a reason for the lower embryo quality of women with PCOS. ABBREVIATIONS: ART: assisted reproductive technology BMI: body mass index COC: cumulus-cell-oocyte complex PCOS: polycystic ovary syndrome q RT-PCR: quantitative real-time PCR TLRs: Toll-like receptors. PMID- 27367830 TI - Trehalase plays a role in macrophage colonization and virulence of Burkholderia pseudomallei in insect and mammalian hosts. AB - Trehalose is a disaccharide formed from two glucose molecules. This sugar molecule can be isolated from a range of organisms including bacteria, fungi, plants and invertebrates. Trehalose has a variety of functions including a role as an energy storage molecule, a structural component of glycolipids and plays a role in the virulence of some microorganisms. There are many metabolic pathways that control the biosynthesis and degradation of trehalose in different organisms. The enzyme trehalase forms part of a pathway that converts trehalose into glucose. In this study we set out to investigate whether trehalase plays a role in both stress adaptation and virulence of Burkholderia pseudomallei. We show that a trehalase deletion mutant (treA) had increased tolerance to thermal stress and produced less biofilm than the wild type B. pseudomallei K96243 strain. We also show that the DeltatreA mutant has reduced ability to survive in macrophages and that it is attenuated in both Galleria mellonella (wax moth larvae) and a mouse infection model. This is the first report that trehalase is important for bacterial virulence. PMID- 27367831 TI - The correlations of socioeconomic status, disease activity, quality of life, and depression/anxiety in Chinese patients with rheumatoid arthritis. AB - This study aimed (i) to investigate the relationships among socioeconomic status, disease activity, quality of life, and the psychological status in Chinese rheumatoid arthritis (RA) patients; (ii) to explore the possible risk factors of anxiety and depression. A total of 160 RA patients underwent standardized laboratory examinations and completed several questionnaires. Independent samples t-tests, chi2 analyses, and logistic regression modeling were used to analyze the data. We found 30.6% RA patients were anxiety, and 27.5% had depression, which were significantly higher than the control group (7.8 and 11.7%, respectively). And there were significant correlations among education, pain, disease activity, medication adherence, functional capacity, quality of life, and anxiety/depression. Meanwhile, logistic regression analysis revealed that poor quality of life and low education level were significantly associated with anxiety/depression in RA patients. In conclusion, there were significant relationships among education, quality of life, and anxiety/depression in Chinese RA patients. PMID- 27367832 TI - Efficacy of Augmentation of Cognitive Behavior Therapy With Weight-Adjusted d Cycloserine vs Placebo in Pediatric Obsessive-Compulsive Disorder: A Randomized Clinical Trial. AB - IMPORTANCE: Cognitive behavior therapy (CBT) among youth with obsessive compulsive disorder (OCD) is effective, but many patients remain symptomatic after intervention. d-cycloserine, a partial agonist at the N-methyl-d-aspartate receptor in the amygdala, has been associated with enhanced CBT outcome for OCD among adults but requires evaluation among youth. OBJECTIVES: To examine the relative efficacy of weight-adjusted d-cycloserine (25 or 50 mg) vs placebo augmentation of CBT for youth with OCD and to assess if concomitant antidepressant medication moderated effects. DESIGN, SETTING, AND PARTICIPANTS: In a placebo-controlled randomized clinical trial, 142 youths (age range, 7-17 years) enrolled between June 1, 2011, and January 30, 2015, at 2 academic health science centers (University of South Florida and Massachusetts General Hospital) with a primary diagnosis of OCD were randomized in a double-blind fashion to d cycloserine plus CBT or placebo plus CBT. Intent-to-treat analysis was performed. INTERVENTIONS: Patients were randomly assigned in a 1:1 ratio to either 10 sessions of d-cycloserine plus CBT or placebo plus CBT. d-cycloserine (25 or 50 mg) or placebo was taken 1 hour before sessions 4 through 10. MAIN OUTCOMES AND MEASURES: Children's Yale-Brown Obsessive Compulsive Scale at randomization, biweekly, midtreatment, and posttreatment. Secondary outcomes included the Clinical Global Impressions-Severity or Clinical Global Impressions-Improvement, remission status, Children's Depression Rating Scale, Multidimensional Anxiety Scale for Children, and Children's Obsessive-Compulsive Impact Scale-Parent Version. RESULTS: The study cohort comprised 142 participants. Their mean (SD) age was 12.7 (2.9) years, and 53.5% (76 of 142) were female. A mixed-effects model using all available data indicated significant declines in the Children's Yale-Brown Obsessive Compulsive Scale total score and Clinical Global Impressions Severity. No significant interaction between treatment group and changes in the Children's Yale-Brown Obsessive Compulsive Scale and Clinical Global Impressions Severity indicated that the d-cycloserine plus CBT group and the placebo plus CBT group declined at similar rates per assessment point on the Children's Yale-Brown Obsessive Compulsive Scale total score (estimate, -2.31, 95% CI, -2.79 to -1.83 and estimate, -2.03, 95% CI, -2.47 to -1.58, respectively) and Clinical Global Impressions-Severity (estimate, -0.29, 95% CI, -0.35 to -0.22 and estimate, 0.23, 95% CI, -0.29 to -0.17, respectively). No group differences in secondary outcomes were present. Antidepressant medication use at baseline did not moderate changes for either group. CONCLUSIONS AND RELEVANCE: d-cycloserine augmentation of CBT did not confer additional benefit relative to placebo among youth with OCD. Other augmentation approaches should be examined to enhance outcome. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00864123. PMID- 27367833 TI - Dystrophin Hot-Spot Mutants Leading to Becker Muscular Dystrophy Insert More Deeply into Membrane Models than the Native Protein. AB - Dystrophin (DYS) is a membrane skeleton protein whose mutations lead to lethal Duchenne muscular dystrophy or to the milder Becker muscular dystrophy (BMD). One third of BMD "in-frame" exon deletions are located in the region that codes for spectrin-like repeats R16 to R21. We focused on four prevalent mutated proteins deleted in this area (called RDelta45-47, RDelta45-48, RDelta45-49, and RDelta45 51 according to the deleted exon numbers), analyzing protein/membrane interactions. Two of the mutants, RDelta45-48 and RDelta45-51, led to mild pathologies and displayed a similar triple coiled-coil structure as the full length DYS R16-21, whereas the two others, RDelta45-47 and RDelta45-49, induced more severe pathologies and showed "fractional" structures unrelated to the normal one. To explore lipid packing, small unilamellar liposomes (SUVs) and planar monolayers were used at various initial surface pressures. The dissociation constants determined by microscale thermophoresis (MST) were much higher for the full-length DYS R161-21 than for the mutants; thus the wild type protein has weaker SUV binding. Comparing surface pressures after protein adsorption and analysis of atomic force microscopy images of mixed protein/lipid monolayers revealed that the mutants insert more into the lipid monolayer than the wild type does. In fact, in both models every deletion mutant showed more interactions with membranes than the full-length protein did. This means that mutations in the R16-21 part of dystrophin disturb the protein's molecular behavior as it relates to membranes, regardless of whether the accompanying pathology is mild or severe. PMID- 27367834 TI - SAR reduction using a single SRR superstrate for a dual-band antenna. AB - A dual-band microstrip antenna operating at GSM 900 and GSM 1800 MHz is designed initially. Then a single split ring resonator (SRR) structure is used as a superstrate for this dual-band antenna. A circular current is induced in the SRR due to the perpendicular plane wave excitation, which in turn leads to an electric excitation coupled to the magnetic resonance. It also exhibits higher order excitations at 0.9 and 1.8 GHz which ultimately resulted in specific absorption rate (SAR) reduction of human head at both the designed frequencies of the antenna. The antenna and the SRR superstrate are printed on a 1.6 mm thick FR 4 substrate of dimension 59.6 * 49.6 mm2. Analysis of the SRR using the classic waveguide theory approach is discussed. Radiation pattern of the antenna in the presence of SRR superstrate and human head is also discussed. Prototype of the antenna along with the SRR superstrate is fabricated and measured for return loss and radiation pattern. Measurement results fairly agree with the simulated results. A human head phantom is utilized in the calculation of SAR. PMID- 27367835 TI - Special Care Dentistry and the Standard of Care. PMID- 27367836 TI - Obsequies for Editorial Debate in a Journal Academic. PMID- 27367837 TI - Lactate as a diagnostic marker in transient loss of consciousness. AB - PURPOSE: The diagnostic classification of disorders of consciousness is often challenging, particularly the distinction between epileptic and non-epileptic seizures. The aim of the study was to examine serum lactate as a diagnostic marker of transient loss of consciousness. METHOD: Serum lactate levels in blood samples drawn within 2h of the event were compared retrospectively between patients with generalized tonic-clonic seizures (n=195) and patients with other seizures (syncopes [n=52], psychogenic non-epileptic seizures [n=17], and complex focal seizures [n=37]), respectively. RESULTS: Serum lactate in patients with generalized tonic-clonic seizures was significantly (p<0.001, Mann-Whitney-U test) increased in comparison to other forms of seizure incidences. The area under the ROC-curve was 0.94 (95% CI 0.91-0.96). For a cut-off concentration of 2.45mmol/l, the sensitivity was 0.88 and the specificity 0.87. CONCLUSIONS: Serum lactate levels in the acute diagnosis were an excellent biomarker for the discrimination of generalized seizures from psychogenic non-epileptic and syncopal events, corroborating its importance for the standard work-up of acute disturbances of consciousness. PMID- 27367838 TI - Status epilepticus secondary to glioma. AB - PURPOSE: Epilepsy is common in glioma patients, but clinical data on the course of status epilepticus (SE) in this group are sparse. The aim of this study was to investigate the relationship of SE to tumor grading, seizure semiology, trigger factors, treatment response, recurrence and outcome of SE in patients with glioma. METHODS: Adult patients with SE and glioma WHO grade II-IV were identified from a prospective clinical study at two neurological departments. We identified 31 SE in 20 patients during a period of 7 years. RESULTS: SE was more frequent in patients with high-grade glioma. Half of the seizures were secondary generalized. Patients with a clinical and radiological stable glioma had SE as often as patients with untreated tumor or tumor in progression. The majority of patients had a well-controlled epilepsy prior to SE. SE responded well to first and second line treatment. Patients with SE and tumor progression were not more refractory to treatment than patients without progression. CONCLUSION: SE secondary to glioma responded well to treatment and should be treated aggressively regardless of the oncological prognosis. Seizures during tumor progression were not more treatment refractory than SE in patients with stable glioma disease. PMID- 27367839 TI - Changes of the optical characteristics of radiochromic films in the transition from EBT3 to EBT-XD films. AB - A new type of radiochromic film, the EBT-XD film, has been introduced with the aim to reduce the orientation effect and the lateral response artifact occurring in the use of radiochromic films together with flatbed scanners. The task of the present study is to quantify the changes of optical characteristics involved with the transition from the well-known EBT3 films to the new EBT-XD films, using the optical bench arrangement already applied by Schoenfeld et al (2014 Phys. Med. Biol. 59 3575-97). Largely reduced polarization effects and the almost complete loss of the anisotropy of the scattered light produced in a radiation-exposed film have been observed. The Rayleigh-Debye-Gans theory is used to understand these optical changes as arising from the reduced length-to-width ratio of the LiPCDA polymer crystals in the active layer of the EBT-XD film. The effect of these changes on the flatbed scanning artifacts will be shortly addressed, but treated in more detail in a further paper. PMID- 27367840 TI - Identification of an alveolar type I epithelial cell-specific DNA nuclear import sequence for gene delivery. AB - The ability to restrict gene delivery and expression to particular cell types is of paramount importance for many types of gene therapy, especially in the lung. The alveolar epithelial type I (ATI) cell, in particular, is an attractive cell type to target, as it comprises 95% of the internal surface area of the lung. We demonstrate, through microinjection of fluorescently labeled plasmids, that a DNA sequence within the rat T1alpha promoter was able to mediate ATI cell-specific plasmid DNA nuclear import due to the binding of ATI-enriched transcription factors. Promoter deletion analysis and site-directed mutagenesis of specific transcription-factor-binding sites within the +101 to -200 bp region of the T1alpha promoter identified HNF3 and TTF-1 as critical transcription factors for import. To test for nuclear import in vivo, plasmids expressing GFP from the CMV promoter were delivered into the lungs of mice by electroporation and evaluated immunohistochemically 48 h later. Plasmids carrying the 1.3 kbp T1alpha sequence resulted in GFP expression almost exclusively in ATI cells. This represents a new and highly efficient way to target a specific lung epithelial cell type both in vitro and in vivo based on the restriction of DNA nuclear import. PMID- 27367841 TI - Long-term, high-level hepatic secretion of acid alpha-glucosidase for Pompe disease achieved in non-human primates using helper-dependent adenovirus. AB - Pompe disease (glycogen storage disease type II (GSD-II)) is a myopathy caused by a genetic deficiency of acid alpha-glucosidase (GAA) leading to lysosomal glycogen accumulation causing muscle weakness, respiratory insufficiency and death. We previously demonstrated in GSD-II mice that a single injection of a helper-dependent adenovirus (HD-Ad) expressing GAA resulted in at least 300 days of liver secretion of GAA, correction of the glycogen storage in cardiac and skeletal muscles and improved muscle strength. Recent reports suggest that gene therapy modeling for lysososomal storage diseases in mice fails to predict outcomes in larger animal models. We therefore evaluated an HD-Ad expressing GAA in non-human primates. The baboons not only tolerated the procedure well, but the results also confirmed that a single dose of the HD-Ad allowed the livers of the treated animals to express and secrete large amounts of GAA for at least 6 months, at levels similar to those achieved in mice. Moreover, we detected liver derived GAA in the heart, diaphragm and skeletal muscles of the treated animals for the duration of the study at levels that corrected glycogen accumulation in mice. This work validates our proof-of-concept studies in mice, and justifies future efforts using Ad-based vectors in Pompe disease patients. PMID- 27367844 TI - Theoretical Study on the Reaction Mechanism of Ti with CH3CN in the Gas Phase. AB - To gain a deeper understanding of the reaction mechanisms of Ti with acetonitrile molecules, the triplet and singlet spin-state potential energy surfaces (PESs) has been investigated at B3LYP level of density functional theory (DFT). Crossing points between the different PESs and possible spin inversion processes are discussed by spin-orbit coupling (SOC) calculation. In addition, the bonding properties of the species along the reaction were analyzed by electron localization function (ELF), atoms in molecules (AIM) and natural bond orbital (NBO). The results showed that acetonitrile activation by Ti is a typical spin forbidden process; larger SOC (by 220.12 cm(-1)) and the possibility of crossing between triplet and singlet imply that intersystem crossing (ISC) would occur near the minimum energy crossing point (MECP) during the transfer of the hydrogen atom. PMID- 27367843 TI - Comparison of Health and Health Risk Factors Between Lesbian, Gay, and Bisexual Adults and Heterosexual Adults in the United States: Results From the National Health Interview Survey. AB - IMPORTANCE: Previous studies identified disparities in health and health risk factors among lesbian, gay, and bisexual (LGB) adults, but prior investigations have been confined to samples not representative of the US adult population or have been limited in size or geographic scope. For the first time in its long history, the 2013 and 2014 National Health Interview Survey included a question on sexual orientation, providing health information on sexual minorities from one of the nation's leading health surveys. OBJECTIVE: To compare health and health risk factors between LGB adults and heterosexual adults in the United States. DESIGN, SETTING, AND PARTICIPANTS: Data from the nationally representative 2013 and 2014 National Health Interview Survey were used to compare health outcomes among lesbian (n = 525), gay (n = 624), and bisexual (n = 515) adults who were 18 years or older and their heterosexual peers (n = 67 150) using logistic regression. MAIN OUTCOMES AND MEASURES: Self-rated health, functional status, chronic conditions, psychological distress, alcohol consumption, and cigarette use. RESULTS: The study cohort comprised 68 814 participants. Their mean (SD) age was 46.8 (11.8) years, and 51.8% (38 063 of 68 814) were female. After controlling for sociodemographic characteristics, gay men were more likely to report severe psychological distress (odds ratio [OR], 2.82; 95% CI, 1.55-5.14), heavy drinking (OR, 1.97; 95% CI, 1.08-3.58), and moderate smoking (OR, 1.98; 95% CI, 1.39-2.81) than heterosexual men; bisexual men were more likely to report severe psychological distress (OR, 4.70; 95% CI, 1.77-12.52), heavy drinking (OR, 3.15; 95% CI, 1.22-8.16), and heavy smoking (OR, 2.10; 95% CI, 1.08-4.10) than heterosexual men; lesbian women were more likely to report moderate psychological distress (OR, 1.34; 95% CI, 1.02-1.76), poor or fair health (OR, 1.91; 95% CI, 1.24-2.95), multiple chronic conditions (OR, 1.58; 95% CI, 1.12-2.22), heavy drinking (OR, 2.63; 95% CI, 1.54-4.50), and heavy smoking (OR, 2.29; 95% CI, 1.36 3.88) than heterosexual women; and bisexual women were more likely to report multiple chronic conditions (OR, 2.07; 95% CI, 1.34-3.20), severe psychological distress (OR, 3.69; 95% CI, 2.19-6.22), heavy drinking (OR, 2.07; 95% CI, 1.20 3.59), and moderate smoking (OR, 1.60; 95% CI, 1.05-2.44) than heterosexual women. CONCLUSIONS AND RELEVANCE: This study supports prior research finding substantial health disparities for LGB adults in the United States, potentially due to the stressors that LGB people experience as a result of interpersonal and structural discrimination. In screening for health issues, clinicians should be sensitive to the needs of sexual minority patients. PMID- 27367842 TI - Glucocorticoid receptor-PPARalpha axis in fetal mouse liver prepares neonates for milk lipid catabolism. AB - In mammals, hepatic lipid catabolism is essential for the newborns to efficiently use milk fat as an energy source. However, it is unclear how this critical trait is acquired and regulated. We demonstrate that under the control of PPARalpha, the genes required for lipid catabolism are transcribed before birth so that the neonatal liver has a prompt capacity to extract energy from milk upon suckling. The mechanism involves a fetal glucocorticoid receptor (GR)-PPARalpha axis in which GR directly regulates the transcriptional activation of PPARalpha by binding to its promoter. Certain PPARalpha target genes such as Fgf21 remain repressed in the fetal liver and become PPARalpha responsive after birth following an epigenetic switch triggered by beta-hydroxybutyrate-mediated inhibition of HDAC3. This study identifies an endocrine developmental axis in which fetal GR primes the activity of PPARalpha in anticipation of the sudden shifts in postnatal nutrient source and metabolic demands. PMID- 27367845 TI - Solution structure of the microtubule-targeting COS domain of MID1. AB - The human MID1 protein is required for the proper development during embryogenesis. Mutations of MID1 are associated with X-linked Opitz G syndrome, characterized by midline anomalies. MID1 associates with the microtubules and functions as an ubiquitin E3 ligase, targeting protein phosphatase 2A for ubiquitin-mediated regulation. The mechanism of microtubule association is not known. Recently, a 60-amino acid region termed the C-terminal subgroup One Signature (COS) box/domain was identified at the C-terminal end of the coiled coil (CC) domain that facilitates microtubule localization. Insertion of the MID1 COS domain at the C-terminal end of the CC domain of a nonmicrotubule-associated TRIM protein confers microtubule localization. Here, we report the solution structure of the COS domain of MID1. The domain adopts a helix-loop-helix structure in which the N- and C-terminal ends are in close proximity. Hydrophobic residues stabilizing the interaction of the two alpha-helices form a central hydrophobic core. The loop separating the alpha-helices is structured, with two of its hydrophobic residues making contact with the central core. On the outer surface, positively charged residues form a distinct basic patch near the termini that we postulate is important for microtubule binding. A model of the structure of the preceding coiled-coil and COS domains (CC-COS) show that the COS domain forms a helical bundle at the C-terminal end of the CC domain similar to the spectrin-like fold observed with some known microtubule-binding proteins. Interestingly, the CC-COS domains bind to microtubules, demonstrating for the first time that MID1 can directly associate with the microtubules. DATABASE: Structural data are available in PDB database under the accession number 5IM8. PMID- 27367847 TI - Erratum. PMID- 27367846 TI - Hypo-CpG methylation controls PTEN expression and cell apoptosis in irradiated lung. AB - PURPOSE: The current study was designed to address our hypothesis that oxidative stress secondary to the ionizing event upregulates phosphatase and tensin homolog (PTEN) mRNA and protein in the lungs of C57BL/6J mice through oxidative DNA damage resulting in CpG hypomethylation in the PTEN promoter. METHODS: Fibrosis prone C57BL/6J mice were exposed to 0 or 15 Gy of 320 kVp X-rays to the whole thorax. Lung tissue was serially harvested at time points between one day and six months postirradiation. Tissue levels of PTEN mRNA, total protein, and phosphorylated PTEN, as well as CpG methylation of the PTEN promoter, expression of DNA methyltransferases 1 (Dnmt1) and 3a (Dnmt3a), NADPH oxidase 4 (Nox4) protein expression, and DNA damage levels were measured. The induction of DNA damage and global methylation changes were also examined in hydrogen peroxide (H2O2)-treated human umbilical vein endothelial cells (HUVECs) and human bronchial epithelial cells in vitro. RESULTS: These experiments demonstrate that PTEN mRNA and protein, Nox4 protein, and DNA damage levels increase continuously from one day to six months following radiation exposure. Elevated PTEN transcription and translation are likely the result of the observed decrease in CpG methylation of the PTEN promoter region. This finding is not consistent with the observed increase in Dnmt1 and Dnmt3a protein expression, implicating an alternative mechanism as the driving force behind hypomethylation. In vitro results provide evidence that H2O2 can induce DNA damage and affect DNA methylation status. The Mn porphyrin-based superoxide dismutase (SOD) mimic MnTnHEx-2-PyP(5+ )exhibited partial rescue from radiation-induced hypomethylation. CONCLUSIONS: Taken together, these data suggest that reactive oxygen species (ROS)-induced DNA damage results in hypomethylation of the PTEN promoter, upregulation of PTEN mRNA and protein, and a subsequent increase in apoptosis in irradiated lung tissue. PMID- 27367848 TI - Super-resolution T1 estimation: Quantitative high resolution T1 mapping from a set of low resolution T1 -weighted images with different slice orientations. AB - PURPOSE: Quantitative T1 mapping is a magnetic resonance imaging technique that estimates the spin-lattice relaxation time of tissues. Even though T1 mapping has a broad range of potential applications, it is not routinely used in clinical practice as accurate and precise high resolution T1 mapping requires infeasibly long acquisition times. METHOD: To improve the trade-off between the acquisition time, signal-to-noise ratio and spatial resolution, we acquire a set of low resolution T1 -weighted images and directly estimate a high resolution T1 map by means of super-resolution reconstruction. RESULTS: Simulation and in vivo experiments show an increased spatial resolution of the T1 map, while preserving a high signal-to-noise ratio and short scan time. Moreover, the proposed method outperforms conventional estimation in terms of root-mean-square error. CONCLUSION: Super resolution T1 estimation enables resolution enhancement in T1 mapping with the use of standard (inversion recovery) T1 acquisition sequences. Magn Reson Med 77:1818-1830, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27367849 TI - An Atypical Case of Mounier-Kuhn Syndrome: Time to Change the Diagnostic Approach? AB - Mounier-Kuhn syndrome (MKS) is a rare disease of unknown etiology characterized by abnormal pathologic dilatation of tracheabronchial tree. The diagnosis of MKS is normally made on CT scan of chest on the basis of enlarged diameters of trachea and main stem bronchi. We are presenting histologically confirmed case of MKS, where the diameter of right main bronchus is below minimum diameter (mean+3 SD) required for the diagnosis. We suggest that the diagnosis of MKS should not be solely based on fixed criteria such as the diameter of airways, but on the basis of the overall clinical, pathologic, and radiologic profile. PMID- 27367850 TI - Spontaneous Regression of Endobronchial Carcinoid Tumor. AB - Spontaneous regression (SR) of cancer refers to partial or complete disappearance of a malignant tumor in the absence of treatment or in the presence of therapy, which is considered inadequate to exert a significant influence on the growth of neoplastic disease. SR is a very rare phenomenon in primary lung cancers. Follow up of these patients is generally either by imaging or bronchoscopy. We present a patient with SR of an endobronchial carcinoid, followed by serial bronchoscopies and biopsy over a 24-month period. PMID- 27367852 TI - Removal of Intrapleural Foreign Body by Medical Thoracoscopy: Report of Two Cases and a Systematic Review of the Literature. AB - Intrapleural foreign body is an uncommon condition, usually encountered in the setting of thoracic trauma, but can rarely complicate diagnostic procedures such as thoracentesis. The management involves urgent identification and removal of the foreign body. Although surgical extraction using thoracotomy or video assisted thoracoscopic surgery under general anesthesia constitutes the primary management strategy, intrapleural foreign body can also be removed using medical thoracoscopy. Herein, we report the successful removal of 2 intrapleural foreign bodies using a rigid thoracoscope under local anesthesia and conscious sedation. We also performed a systematic review of the literature describing the use of medical thoracoscopy in the retrieval of an intrapleural foreign body. PMID- 27367854 TI - Resveratrol-Mediated Repression and Reversion of Prostatic Myofibroblast Phenoconversion. AB - BACKGROUND: Resveratrol, a phytoalexin found in berries, peanuts, grapes, and red wine, inhibits oxidation, inflammation, and cell proliferation and collagen synthesis in multiple cell types and or animal models. It represses collagen deposition in the vasculature, heart, lung, kidney, liver, and esophagus in animal models and may have some utility as an anti-fibrotic. Recent studies have shown that increased collagen deposition and tissue stiffness in the peri urethral area of the prostate are associated with lower urinary tract dysfunction (LUTD) and urinary obstructive symptoms. The aim of this study was to determine whether Resveratrol might be useful to inhibit or revert TGFbeta- and/or CXCL12 mediated myofibroblast phenoconversion of prostate fibroblasts in vitro, and therefore whether the use of anti-fibrotic therapeutics might be efficacious for the treatment of LUTD. METHODS: Primary prostate and lung tissues were explanted and fibroblast monolayers expanded in vitro. Primary and N1 immortalized prostate stromal fibroblasts, as well as primary fibroblasts cultured from a normal lung and one affected by idiopathic pulmonary fibrosis (IPF) for comparison, were grown in serum-free defined media supplemented with vehicle, TGFbeta or CXCL12, pre- or post-treatment with Resveratrol, and were evaluated using immunofluorescence for alpha smooth muscle actin (alphaSMA) and collagen I (COL1) protein expression and assessed for cell proliferation, apoptosis, and COL1 and EGR1 transcript expression. RESULTS: This study showed that low concentrations of Resveratrol (<=50 MUM) had no effect on N1 or primary prostate fibroblast cell proliferation, apoptosis, or COL1 or EGR1 gene transcription but repressed and reversed myofibroblast phenoconversion. As expected, these same effects were observed for IPF lung fibroblasts though higher levels of Resveratrol (>=100uM) were required. Taken together, these data suggest that, like lung fibroblasts, prostate fibroblast to myofibroblast phenoconversion can be both repressed and reversed by Resveratrol treatment. Thus, anti-fibrotic therapeutics might be efficacious for the treatment of LUTD. PMID- 27367856 TI - Strategies for Health System Innovation After Gobeille v Liberty Mutual Insurance Company. PMID- 27367855 TI - Supplementation with Selenium and Coenzyme Q10 Reduces Cardiovascular Mortality in Elderly with Low Selenium Status. A Secondary Analysis of a Randomised Clinical Trial. AB - BACKGROUND: Selenium is needed by all living cells in order to ensure the optimal function of several enzyme systems. However, the selenium content in the soil in Europe is generally low. Previous reports indicate that a dietary supplement of selenium could reduce cardiovascular disease but mainly in populations in low selenium areas. The objective of this secondary analysis of a previous randomised double-blind placebo-controlled trial from our group was to determine whether the effects on cardiovascular mortality of supplementation with a fixed dose of selenium and coenzyme Q10 combined during a four-year intervention were dependent on the basal level of selenium. METHODS: In 668 healthy elderly individuals from a municipality in Sweden, serum selenium concentration was measured. Of these, 219 individuals received daily supplementation with selenium (200 MUg Se as selenized yeast) and coenzyme Q10 (200 mg) combined for four years. The remaining participants (n = 449) received either placebo (n = 222) or no treatment (n = 227). All cardiovascular mortality was registered. No participant was lost during a median follow-up of 5.2 years. Based on death certificates and autopsy results, all mortality was registered. FINDINGS: The mean serum selenium concentration among participants at baseline was low, 67.1 MUg/L. Based on the distribution of selenium concentration at baseline, the supplemented group was divided into three groups; <65 MUg/L, 65-85 MUg/L, and >85 MUg/L (45 and 90 percentiles) and the remaining participants were distributed accordingly. Among the non-treated participants, lower cardiovascular mortality was found in the high selenium group as compared with the low selenium group (13.0% vs. 24.1%; P = 0.04). In the group with the lowest selenium basal concentration, those receiving placebo or no supplementation had a mortality of 24.1%, while mortality was 12.1% in the group receiving the active substance, which was an absolute risk reduction of 12%. In the middle selenium concentration group a mortality of 14.0% in the non-treated group, and 6.0% in the actively treated group could be demonstrated; thus, there was an absolute risk reduction of 8.0%. In the group with a serum concentration of >85 MUg/L, a cardiovascular mortality of 17.5% in the non-treated group, and 13.0% in the actively treated group was observed. No significant risk reduction by supplementation could thus be found in this group. CONCLUSIONS: In this evaluation of healthy elderly Swedish municipality members, two important results could be reported. Firstly, a low mean serum selenium concentration, 67 MUg/L, was found among the participants, and the cardiovascular mortality was higher in the subgroup with the lower selenium concentrations <65 MUg/L in comparison with those having a selenium concentration >85 MUg/L. Secondly, supplementation was cardio-protective in those with a low selenium concentration, <=85 at inclusion. In those with serum selenium>85 MUg/L and no apparent deficiency, there was no effect of supplementation. This is a small study, but it presents interesting data, and more research on the impact of lower selenium intake than recommended is therefore warranted. TRIAL REGISTRATION: Clinicaltrials.gov NCT01443780. PMID- 27367857 TI - Sensitivity of Above-Ground Biomass Estimates to Height-Diameter Modelling in Mixed-Species West African Woodlands. AB - It has been suggested that above-ground biomass (AGB) inventories should include tree height (H), in addition to diameter (D). As H is a difficult variable to measure, H-D models are commonly used to predict H. We tested a number of approaches for H-D modelling, including additive terms which increased the complexity of the model, and observed how differences in tree-level predictions of H propagated to plot-level AGB estimations. We were especially interested in detecting whether the choice of method can lead to bias. The compared approaches listed in the order of increasing complexity were: (B0) AGB estimations from D only; (B1) involving also H obtained from a fixed-effects H-D model; (B2) involving also species; (B3) including also between-plot variability as random effects; and (B4) involving multilevel nested random effects for grouping plots in clusters. In light of the results, the modelling approach affected the AGB estimation significantly in some cases, although differences were negligible for some of the alternatives. The most important differences were found between including H or not in the AGB estimation. We observed that AGB predictions without H information were very sensitive to the environmental stress parameter (E), which can induce a critical bias. Regarding the H-D modelling, the most relevant effect was found when species was included as an additive term. We presented a two-step methodology, which succeeded in identifying the species for which the general H-D relation was relevant to modify. Based on the results, our final choice was the single-level mixed-effects model (B3), which accounts for the species but also for the plot random effects reflecting site-specific factors such as soil properties and degree of disturbance. PMID- 27367858 TI - Burkholderia pseudomallei Differentially Regulates Host Innate Immune Response Genes for Intracellular Survival in Lung Epithelial Cells. AB - BACKGROUND: Burkholderia pseudomallei, the causative agent of melioidosis poses a serious threat to humankind. B. pseudomallei secretes numerous virulence proteins that alter host cell functions to escape from intracellular immune sensors. However, the events underlying disease pathogenesis are poorly understood. METHODS: We determined the ability of B. pseudomallei to invade and survive intracellularly in A549 human lung epithelial cells, and also investigated the early transcriptional responses using an Illumina HumanHT-12 v4 microarray platform, after three hours of exposure to live B. pseudomallei (BCMS) and its secreted proteins (CCMS). RESULTS: We found that the ability of B. pseudomallei to invade and survive intracellularly correlated with increase of multiplicity of infection and duration of contact. Activation of host carbohydrate metabolism and apoptosis as well as suppression of amino acid metabolism and innate immune responses both by live bacteria and its secreted proteins were evident. These early events might be linked to initial activation of host genes directed towards bacterial dissemination from lungs to target organs (via proposed in vivo mechanisms) or to escape potential sensing by macrophages. CONCLUSION: Understanding the early responses of A549 cells toward B. pseudomallei infection provide preliminary insights into the likely pathogenesis mechanisms underlying melioidosis, and could contribute to development of novel intervention strategies to combat B. pseudomallei infections. PMID- 27367860 TI - Author Disambiguation in PubMed: Evidence on the Precision and Recall of Author ity among NIH-Funded Scientists. AB - We examined the usefulness (precision) and completeness (recall) of the Author ity author disambiguation for PubMed articles by associating articles with scientists funded by the National Institutes of Health (NIH). In doing so, we exploited established unique identifiers-Principal Investigator (PI) IDs-that the NIH assigns to funded scientists. Analyzing a set of 36,987 NIH scientists who received their first R01 grant between 1985 and 2009, we identified 355,921 articles appearing in PubMed that would allow us to evaluate the precision and recall of the Author-ity disambiguation. We found that Author-ity identified the NIH scientists with 99.51% precision across the articles. It had a corresponding recall of 99.64%. Precision and recall, moreover, appeared stable across common and uncommon last names, across ethnic backgrounds, and across levels of scientist productivity. PMID- 27367859 TI - Red-Shifted Aequorin Variants Incorporating Non-Canonical Amino Acids: Applications in In Vivo Imaging. AB - The increased importance of in vivo diagnostics has posed new demands for imaging technologies. In that regard, there is a need for imaging molecules capable of expanding the applications of current state-of-the-art imaging in vivo diagnostics. To that end, there is a desire for new reporter molecules capable of providing strong signals, are non-toxic, and can be tailored to diagnose or monitor the progression of a number of diseases. Aequorin is a non-toxic photoprotein that can be used as a sensitive marker for bioluminescence in vivo imaging. The sensitivity of aequorin is due to the fact that bioluminescence is a rare phenomenon in nature and, therefore, it does not suffer from autofluorescence, which contributes to background emission. Emission of bioluminescence in the blue-region of the spectrum by aequorin only occurs when calcium, and its luciferin coelenterazine, are bound to the protein and trigger a biochemical reaction that results in light generation. It is this reaction that endows aequorin with unique characteristics, making it ideally suited for a number of applications in bioanalysis and imaging. Herein we report the site specific incorporation of non-canonical or non-natural amino acids and several coelenterazine analogues, resulting in a catalog of 72 cysteine-free, aequorin variants which expand the potential applications of these photoproteins by providing several red-shifted mutants better suited to use in vivo. In vivo studies in mouse models using the transparent tissue of the eye confirmed the activity of the aequorin variants incorporating L-4-iodophehylalanine and L-4 methoxyphenylalanine after injection into the eye and topical addition of coelenterazine. The signal also remained localized within the eye. This is the first time that aequorin variants incorporating non-canonical amino acids have shown to be active in vivo and useful as reporters in bioluminescence imaging. PMID- 27367861 TI - Implicit emotion regulation in the context of viewing artworks: ERP evidence in response to pleasant and unpleasant pictures. AB - Presenting affective pictures as a work of art could change perceivers' judgment and strength in emotional reactions. Aesthetic theory states that perceivers of art emotionally distance themselves, allowing them to appreciate works of art depicting gruesome events. To examine whether implicit emotion regulation is induced by an art context, we assessed whether presenting pleasant and unpleasant IAPS pictures as either "works of art comprising paintings, digital renderings, and photographs of staged scenes" or "photographs depicting real events" modulated perceivers' Late Positive Potentials (LPP) and likability ratings. In line with previous research and aesthetic theory, participants evaluated the IAPS pictures as more likable when they were presented as works of art than when they were presented as photographs. Moreover, participants' late LPP amplitudes (600 900ms post picture onset) in response to the pictures were attenuated in the art context condition. These results provide evidence for an implicit emotion regulation induced by the art context. PMID- 27367862 TI - Combining EEG and eye movement recording in free viewing: Pitfalls and possibilities. AB - Co-registration of EEG and eye movement has promise for investigating perceptual processes in free viewing conditions, provided certain methodological challenges can be addressed. Most of these arise from the self-paced character of eye movements in free viewing conditions. Successive eye movements occur within short time intervals. Their evoked activity is likely to distort the EEG signal during fixation. Due to the non-uniform distribution of fixation durations, these distortions are systematic, survive across-trials averaging, and can become a source of confounding. We illustrate this problem with effects of sequential eye movements on the evoked potentials and time-frequency components of EEG and propose a solution based on matching of eye movement characteristics between experimental conditions. The proposal leads to a discussion of which eye movement characteristics are to be matched, depending on the EEG activity of interest. We also compare segmentation of EEG into saccade-related epochs relative to saccade and fixation onsets and discuss the problem of baseline selection and its solution. Further recommendations are given for implementing EEG-eye movement co registration in free viewing conditions. By resolving some of the methodological problems involved, we aim to facilitate the transition from the traditional stimulus-response paradigm to the study of visual perception in more naturalistic conditions. PMID- 27367863 TI - Assessment of histological differentiation in gastric cancers using whole-volume histogram analysis of apparent diffusion coefficient maps. AB - PURPOSE: To investigate the efficacy of histogram analysis of the entire tumor volume in apparent diffusion coefficient (ADC) maps for differentiating between histological grades in gastric cancer. MATERIALS AND METHODS: Seventy-eight patients with gastric cancer were enrolled in a retrospective 3.0T magnetic resonance imaging (MRI) study. ADC maps were obtained at two different b values (0 and 1000 sec/mm2 ) for each patient. Tumors were delineated on each slice of the ADC maps, and a histogram for the entire tumor volume was subsequently generated. A series of histogram parameters (eg, skew and kurtosis) were calculated and correlated with the histological grade of the surgical specimen. The diagnostic performance of each parameter for distinguishing poorly from moderately well-differentiated gastric cancers was assessed by using the area under the receiver operating characteristic curve (AUC). RESULTS: There were significant differences in the 5th , 10th , 25th , and 50th percentiles, skew, and kurtosis between poorly and well-differentiated gastric cancers (P < 0.05). There were correlations between the degrees of differentiation and histogram parameters, including the 10th percentile, skew, kurtosis, and max frequency; the correlation coefficients were 0.273, -0.361, -0.339, and -0.370, respectively. Among all the histogram parameters, the max frequency had the largest AUC value, which was 0.675. CONCLUSION: Histogram analysis of the ADC maps on the basis of the entire tumor volume can be useful in differentiating between histological grades for gastric cancer. LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;45:440-449. PMID- 27367864 TI - A Systematic Review of the Impact of Potentially Inappropriate Medication on Health Care Utilization and Costs Among Older Adults. AB - BACKGROUND: Potentially inappropriate medications (PIMs) are defined as those medicines having a greater potential risk than benefit for older adults. In this systematic literature review, we evaluate the current evidence on health care service use and health care costs associated with PIMs among older adults. METHODS: A literature search was conducted in August 2015 without publication date restrictions using the databases PubMed and Scopus. Selected articles included in the review of articles were: (1) observational cohort or case control, or intervention studies; (2) investigating PIM use among older adults aged 65 years or older with outcomes on health care utilization (eg, hospitalization) or health care costs; and (3) use of some published criteria for assessing PIMs. RESULTS: Of 825 abstracts screened, in total 51 articles proceeded to full-text review. Of those full-text articles, 39 articles were included in this review. Most of the articles found that PIMs had a statistically significant effect on health care service use, especially on hospitalization, among older adults. The findings of impact on length of stay or readmissions were inconclusive. Five studies found statistically significant higher medical or total health care costs for PIM users compared those who did not use any PIMs. CONCLUSIONS: PIMs can, in addition to health and quality of life problems, also lead to greater health care service use and, thus, higher health care costs. However, the heterogeneity of the study settings makes the interpretation of the results difficult. Further studies, especially on economic issues with country specific criteria, are needed. PMID- 27367865 TI - Impact of ACA Insurance Coverage Expansion on Perforated Appendix Rates Among Young Adults. AB - BACKGROUND: The 2010 Dependent Coverage Provision (DCP) of the Affordable Care Act allowed young adults to remain on their parents' health insurance plans until age 26 years. Although the provision improved coverage and survey-reported access to care, little is known regarding its impact on timely access for acute conditions. This study aims to assess changes in insurance coverage and perforation rates among young adults with acute appendicitis-an established metric for population-level health care access-after the DCP. METHODS: The National Inpatient Sample and difference-in-differences linear regression were used to assess prepolicy/postpolicy changes for policy-eligible young adults (aged 19-25 y) compared with a slightly older, policy-ineligible comparator group (aged 26-34 y). RESULTS: After adjustment for covariates, 19-25 year olds experienced a 3.6-percentage point decline in the uninsured rate after the DCP (baseline 22.5%), compared with 26-34 year olds (P<0.001). This coincided with a 1.4-percentage point relative decline in perforated appendix rate for 19-25 year olds (baseline 17.5%), compared with 26-34 year olds (P=0.023). All subgroups showed significant reductions in uninsured rates; however, statistically significant reductions in perforation rates were limited to racial/ethnic minorities, patients from lower-income communities, and patients presenting to urban teaching hospitals. CONCLUSIONS: Reductions in uninsured rates among young adults after the DCP were associated with significant reductions in perforated appendix rates relative to a comparator group, suggesting that insurance expansion could lead to fewer delays in seeking and accessing care for acute conditions. Greater relative declines in perforation rates among the most at-risk subpopulations hold important implications for the use of coverage expansion to mitigate existing disparities in access to care. PMID- 27367866 TI - The Impact of Using Mid-level Providers in Face-to-Face Primary Care on Health Care Utilization. AB - BACKGROUND: There has been concern that greater use of nurse practitioners (NP) and physician assistants (PA) in face-to-face primary care may increase utilization and spending. OBJECTIVE: To evaluate a natural experiment within Kaiser Permanente in Georgia in the use of NP/PA in primary care. STUDY DESIGN: From 2006 through early 2008 (the preperiod), each NP or PA was paired with a physician to manage a patient panel. In early 2008, NPs and PAs were removed from all face-to-face primary care. Using the 2006-2010 data, we applied a difference in-differences analytic approach at the clinic level due to patient triage between a NP/PA and a physician. Clinics were classified into 3 different groups based on the percentage of visits by NP/PA during the preperiod: high (over 20% in-person primary care visits attended by NP/PAs), medium (5%-20%), and low (<5%) NP/PA model clinics. MEASURES: Referrals to specialist physicians; emergency department visits and inpatient admissions; and advanced diagnostic imaging services. RESULTS: Compared with the low NP/PA model, the high NP/PA model and the medium NP/PA model were associated with 4.9% and 5.1% fewer specialist referrals, respectively (P<0.05 for both estimates); the high NP/PA model and the medium NP/PA model also showed fewer hospitalizations and emergency department visits and fewer advanced diagnostic imaging services, but none of these was statistically significant. CONCLUSIONS: We find no evidence to support concerns that under a physician's supervision, NPs and PAs increase utilization and spending. PMID- 27367867 TI - Low Use of Oral Anticoagulant Prescribing for Secondary Stroke Prevention: Results From the Ontario Stroke Registry. AB - BACKGROUND: Oral anticoagulation reduces the risk of stroke in atrial fibrillation but is often underused. OBJECTIVES: To identify factors associated with oral anticoagulant prescribing and adherence after stroke or transient ischemic attack (TIA). RESEARCH DESIGN: Retrospective cohort study using linked Ontario Stroke Registry and prescription claims data. SUBJECTS: Consecutive patients with atrial fibrillation and ischemic stroke/TIA admitted to 11 stroke centers in Ontario, Canada between 2003 and 2011. MEASURES: We used modified Poisson regression models to determine predictors of anticoagulant prescribing and multiple logistic regression to determine predictors of 1-year adherence. RESULTS: Of the 5781 patients in the study cohort, 4235 (73%) were prescribed oral anticoagulants at discharge. Older patients were less likely to receive anticoagulation [adjusted relative risk (aRR) for each additional year=0.997; 95% confidence interval (CI), 0.995-0.998], as were those with TIA compared with ischemic stroke (aRR=0.904; 95% CI, 0.865-0.945), prior gastrointestinal bleed (aRR=0.778; 95% CI, 0.693-0.873), dementia (aRR=0.912; 95% CI, 0.856-0.973), and those from a long-term care facility (aRR=0.810; 95% CI, 0.737-0.891). After limiting the sample to those without obvious contraindications to anticoagulation, age, dementia, and long-term care residence continued to be associated with lower prescription of oral anticoagulants. One-year adherence to therapy was similar across most patient groups. CONCLUSIONS: Age, dementia, and long-term care residence are predictors of lower oral anticoagulant use for secondary stroke prevention and represent key target areas for quality improvement initiatives. PMID- 27367868 TI - Comorbidity Correlates of Death Among New Veterans of Iraq and Afghanistan Deployment. AB - BACKGROUND: Veterans of the wars in Iraq and Afghanistan who receive care in the Veterans Health Administration (VA) have high disease burden. Distinct comorbidity patterns have been shown to be differentially associated with adverse outcomes, including death. This study determined correlates of 5-year mortality. MATERIALS AND METHODS: VA demographic, military, homelessness, and clinical measures informed this retrospective analysis. Previously constructed comorbidity classifications over 3 years of care were entered into a Cox proportional hazards model of death. RESULTS: There were 164,933 veterans in the cohort, including African Americans (16%), Hispanics (11%), and whites (65%). Most were in their 20s at baseline (60%); 12% were women; 4% had attempted suicide; 4% had been homeless. Having clustered disorders of pain, posttraumatic stress disorder, and traumatic brain injury was associated with death [hazard ratio (HR)=2.0]. Mental disorders including substance abuse were similarly associated (HR=2.1). Prior suicide attempt (HR=2.2) or drug overdose (HR=3.0) considerably increased risk of death over 5 years. CONCLUSIONS: As congressional actions such as Veterans Choice Act offer more avenues to seek care outside of VA, coordination of care, and suicide prevention outreach for recent veterans may require innovative approaches to preserve life. PMID- 27367869 TI - Microfluidic fuel cells for energy generation. AB - Sustainable energy generation is of recent interest due to a growing energy demand across the globe and increasing environmental issues caused by conventional non-renewable means of power generation. In the context of microsystems, portable electronics and lab-on-a-chip based (bio)chemical sensors would essentially require fully integrated, reliable means of power generation. Microfluidic-based fuel cells can offer unique advantages compared to conventional fuel cells such as high surface area-to-volume ratio, ease of integration, cost effectiveness and portability. Here, we summarize recent developments which utilize the potential of microfluidic devices for energy generation. PMID- 27367874 TI - High-Intensity Focused Ultrasound for Prostate Cancer: Novelty or Innovation? PMID- 27367870 TI - Rosmarinic acid protects against chronic ethanol-induced learning and memory deficits in rats. AB - OBJECTIVES: Ethanol consumption induces neurological disorders including cognitive dysfunction. Oxidative damage is considered a likely cause of cognitive deficits. We aimed to investigate the effects of rosmarinic acid (RA) in different doses for 30 days on chronic ethanol-induced cognitive dysfunction using the passive avoidance learning (PAL) and memory task in comparison with donepezil, a reference drug. We also evaluated the levels of superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation in hippocampus as possible mechanisms. METHODS: Memory impairment was induced by 15% w/v ethanol (2 g/kg, i.g.) administration for 30 days. RA (8, 16, and 32 mg/kg, i.g.) or donepezil (2 mg/kg, i.g.) was administered 30 minutes before ethanol. The acquisition trial was done 1 hour after the last administration of RA and donepezil. At the end, animals were weighed and hippocami were isolated for analyzing of oxidant/antioxidant markers. RESULTS: Ethanol caused cognition deficits in the PAL and memory task. While RA 16 and 32 mg/kg improved cognition in control rats, it prevented learning and memory deficits of alcoholic groups. RA 8 mg/kg did not influence cognitive function in both control and alcoholic rats. RA 32 mg/kg had comparable effects with donepezil in prevention of acquisition and retention memory impairment. The higher doses of RA not only prevented increased lipid peroxidation and nitrite content but also decreased SOD, CAT, GSH, and FRAP levels in alcoholic groups and exerted antioxidant effects in non-alcoholic rats. DISCUSSION: We showed that RA administration dose-dependently prevented cognitive impairment induced by chronic ethanol in PAL and memory and disturbed oxidant/antioxidant status as a possible mechanism. The antioxidant, anticholinesterase, and neuroprotective properties of RA may be involved in the observed effects. Therefore, RA represents a potential therapeutic option against chronic ethanol-induced amnesia which deserves consideration and further examination. PMID- 27367875 TI - A PIECE OF MY MIND. The Hunger Games. PMID- 27367879 TI - JAMA PATIENT PAGE. Generic Drugs. PMID- 27367876 TI - Effect of Escitalopram on All-Cause Mortality and Hospitalization in Patients With Heart Failure and Depression: The MOOD-HF Randomized Clinical Trial. AB - IMPORTANCE: Depression is frequent in patients with heart failure and is associated with adverse clinical outcomes. Long-term efficacy and safety of selective serotonin reuptake inhibitors in these patients are unknown. OBJECTIVE: To determine whether 24 months of treatment with escitalopram improves mortality, morbidity, and mood in patients with chronic systolic heart failure and depression. DESIGN, SETTING, AND PARTICIPANTS: The Effects of Selective Serotonin Re-Uptake Inhibition on Morbidity, Mortality, and Mood in Depressed Heart Failure Patients (MOOD-HF) study was a double-blind, placebo-controlled randomized clinical trial conducted at 16 tertiary medical centers in Germany. Between March 2009 and February 2014, patients at outpatient clinics with New York Heart Association class II-IV heart failure and reduced left ventricular ejection fraction (<45%) were screened for depression using the 9-item Patient Health Questionnaire. Patients with suspected depression were then invited to undergo a Structured Clinical Interview based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) to establish the diagnosis. INTERVENTIONS: Patients were randomized 1:1 to receive escitalopram (10-20 mg) or matching placebo in addition to optimal heart failure therapy. Study duration was 24 months. MAIN OUTCOMES AND MEASURES: The composite primary outcome was time to all cause death or hospitalization. Prespecified secondary outcomes included safety and depression severity at 12 weeks of treatment (including the titration period), which were determined using the 10-item Montgomery-Asberg Depression Rating Scale (total possible score, 0 to 60; higher scores indicate more severe depression). RESULTS: A total of 372 patients (mean age, 62 years; 24% female) were randomized and had taken at least 1 dose of study medication when the data and safety monitoring committee recommended the trial be stopped early. During a median participation time of 18.4 months (n = 185) for the escitalopram group and 18.7 months (n = 187) for the placebo group, the primary outcome of death or hospitalization occurred in 116 (63%) patients and 119 (64%) patients, respectively (hazard ratio, 0.99 [95% CI, 0.76 to 1.27]; P = .92). The mean Montgomery-Asberg Depression Rating Scale sum score changed from 20.2 at baseline to 11.2 at 12 weeks in the escitalopram group and from 21.4 to 12.5 in the placebo group (between-group difference, -0.9 [95% CI,-2.6 to 0.7]; P = .26). Safety parameters were comparable between groups. CONCLUSIONS AND RELEVANCE: In patients with chronic heart failure with reduced ejection fraction and depression, 18 months of treatment with escitalopram compared with placebo did not significantly reduce all-cause mortality or hospitalization, and there was no significant improvement in depression. These findings do not support the use of escitalopram in patients with chronic systolic heart failure and depression. TRIAL REGISTRATION: isrctn.com Identifier: ISRCTN33128015. PMID- 27367880 TI - IFN Deficiency in Asthma Attacks. Is Restoring Toll-like Receptor-7 Expression a New Treatment Approach in Severe Asthma? PMID- 27367881 TI - Association between Impaired Lung Function and Cardiovascular Disease. Cause, Effect, or Force of Circumstance? PMID- 27367877 TI - Effect of a Primary Care Management Intervention on Mental Health-Related Quality of Life Among Survivors of Sepsis: A Randomized Clinical Trial. AB - IMPORTANCE: Survivors of sepsis face long-term sequelae that diminish health related quality of life and result in increased care needs in the primary care setting, such as medication, physiotherapy, or mental health care. OBJECTIVE: To examine if a primary care-based intervention improves mental health-related quality of life. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted between February 2011 and December 2014, enrolling 291 patients 18 years or older who survived sepsis (including septic shock), recruited from 9 intensive care units (ICUs) across Germany. INTERVENTIONS: Participants were randomized to usual care (n = 143) or to a 12-month intervention (n = 148). Usual care was provided by their primary care physician (PCP) and included periodic contacts, referrals to specialists, and prescription of medication, other treatment, or both. The intervention additionally included PCP and patient training, case management provided by trained nurses, and clinical decision support for PCPs by consulting physicians. MAIN OUTCOMES AND MEASURES: The primary outcome was change in mental health-related quality of life between ICU discharge and 6 months after ICU discharge using the Mental Component Summary (MCS) of the 36-Item Short-Form Health Survey (SF-36 [range, 0-100; higher ratings indicate lower impairment; minimal clinically important difference, 5 score points]). RESULTS: The mean age of the 291 patients was 61.6 years (SD, 14.4); 66.2% (n = 192) were men, and 84.4% (n = 244) required mechanical ventilation during their ICU stay (median duration of ventilation, 12 days [range, 0-134]). At 6 and 12 months after ICU discharge, 75.3% (n = 219 [112 intervention, 107 control]) and 69.4% (n = 202 [107 intervention, 95 control]), respectively, completed follow-up. Overall mortality was 13.7% at 6 months (40 deaths [21 intervention, 19 control]) and 18.2% at 12 months (53 deaths [27 intervention, 26 control]). Among patients in the intervention group, 104 (70.3%) received the intervention at high levels of integrity. There was no significant difference in change of mean MCS scores (intervention group mean at baseline, 49.1; at 6 months, 52.9; change, 3.79 score points [95% CI, 1.05 to 6.54] vs control group mean at baseline, 49.3; at 6 months, 51.0; change, 1.64 score points [95% CI, -1.22 to 4.51]; mean treatment effect, 2.15 [95% CI, -1.79 to 6.09]; P = .28). CONCLUSIONS AND RELEVANCE: Among survivors of sepsis and septic shock, the use of a primary care-focused team-based intervention, compared with usual care, did not improve mental health-related quality of life 6 months after ICU discharge. Further research is needed to determine if modified approaches to primary care management may be more effective. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN61744782. PMID- 27367882 TI - Barriers to Understanding the Epidemiology of Noncommunicable Lung Disease in Sub Saharan Africa. PMID- 27367883 TI - Galectin-3: Distant Biomarker or Relevant Target? PMID- 27367884 TI - Does Breathing Amplify Fibrosis? PMID- 27367885 TI - Marker Games: Seeking Better Biomarkers? PMID- 27367886 TI - Update in Critical Care 2015. AB - This review documents important progress made in 2015 in the field of critical care. Significant advances in 2015 included further evidence for early implementation of low tidal volume ventilation as well as new insights into the role of open lung biopsy, diaphragmatic dysfunction, and a potential mechanism for ventilator-induced fibroproliferation. New therapies, including a novel low flow extracorporeal CO2 removal technique and mesenchymal stem cell-derived microparticles, have also been studied. Several studies examining the role of improved diagnosis and prevention of ventilator-associated pneumonia also showed relevant results. This review examines articles published in the American Journal of Respiratory and Critical Care Medicine and other major journals that have made significant advances in the field of critical care in 2015. PMID- 27367887 TI - A Critical Care Societies Collaborative Statement: Burnout Syndrome in Critical Care Health-care Professionals. A Call for Action. AB - Burnout syndrome (BOS) occurs in all types of health-care professionals and is especially common in individuals who care for critically ill patients. The development of BOS is related to an imbalance of personal characteristics of the employee and work-related issues or other organizational factors. BOS is associated with many deleterious consequences, including increased rates of job turnover, reduced patient satisfaction, and decreased quality of care. BOS also directly affects the mental health and physical well-being of the many critical care physicians, nurses, and other health-care professionals who practice worldwide. Until recently, BOS and other psychological disorders in critical care health-care professionals remained relatively unrecognized. To raise awareness of BOS, the Critical Care Societies Collaborative (CCSC) developed this call to action. The present article reviews the diagnostic criteria, prevalence, causative factors, and consequences of BOS. It also discusses potential interventions that may be used to prevent and treat BOS. Finally, we urge multiple stakeholders to help mitigate the development of BOS in critical care health-care professionals and diminish the harmful consequences of BOS, both for critical care health-care professionals and for patients. PMID- 27367888 TI - First Real-Time Visualization of a Spontaneous Pneumothorax Developing in a Preterm Lamb Using Electrical Impedance Tomography. PMID- 27367889 TI - Effect of Anti-IL-13 Treatment on Airway Dimensions in Severe Asthma. PMID- 27367890 TI - Transbronchial Needle Aspiration for Peripheral Lung Lesions: The Dark Horse Winner of the AQuIRE Registry, or Is It? PMID- 27367891 TI - Electromagnetic Guidance for the Diagnosis of Pulmonary Nodules: Don't Put the Nail in the Coffin. PMID- 27367892 TI - Reply: Quantifying the Benefits of Peripheral Transbronchial Needle Aspiration. PMID- 27367893 TI - Reply: Intratracheal Budesonide/Surfactant for Preventing Bronchopulmonary Dysplasia. PMID- 27367894 TI - Intratracheal Budesonide/Surfactant for Preventing Bronchopulmonary Dysplasia. PMID- 27367896 TI - Erratum. PMID- 27367895 TI - What is Burnout Syndrome (BOS)? PMID- 27367898 TI - Mothercraft: Birth work and the making of neoliberal mothers. AB - The literature on neoliberal health governance explores how macro-economic neoliberal policies as well as individual attitudes and behaviors reflect an increasingly individualized construction of health and citizens' responsibility over it. This study contributes to this literature and expands it in important ways. Drawing on qualitative interviews from 22 midwives and birth workers (doulas, childbirth educators, lactation consultants) practicing in the US, this study explores how midwives and birth workers act as "experts of conduct" who promote certain neoliberal values in their logics of care and interactions with clientele. The findings reveal that midwives and birth workers promote a form of maternal neoliberal health governance by: 1) making distinctions between their clientele that signal differences in health competence and resources, 2) encouraging autonomy and responsibility over birth experiences, and 3) promoting an empowerment discourse that hinges implicitly on an exclusionary consumer choice rhetoric. Midwives and birth workers are crucially implicated in shaping maternal subjectivities through pedagogical interactions I refer to as "mothercraft." This study illustrates how the promotion of certain health identities by experts further stratifies patient populations, exacerbating differences between women based on their socioeconomic status, racial-ethnic, and cultural positions. PMID- 27367897 TI - Education and alcohol use: A study of gene-environment interaction in young adulthood. AB - The consequences of heavy alcohol use remain a serious public health problem. Consistent evidence has demonstrated that both genetic and social influences contribute to alcohol use. Research on gene-environment interaction (GxE) has also demonstrated that these social and genetic influences do not act independently. Instead, certain environmental contexts may limit or exacerbate an underlying genetic predisposition. However, much of the work on GxE and alcohol use has focused on adolescence and less is known about the important environmental contexts in young adulthood. Using data from the young adult wave of the Finnish Twin Study, FinnTwin12 (N = 3402), we used biometric twin modeling to test whether education moderated genetic risk for alcohol use as assessed by drinking frequency and intoxication frequency. Education is important because it offers greater access to personal resources and helps determine one's position in the broader stratification system. Results from the twin models show that education did not moderate genetic variance components and that genetic risk was constant across levels of education. Instead, education moderated environmental variance so that under conditions of low education, environmental influences explained more of the variation in alcohol use outcomes. The implications and limitations of these results are discussed. PMID- 27367899 TI - High performance in healthcare priority setting and resource allocation: A literature- and case study-based framework in the Canadian context. AB - Priority setting and resource allocation, or PSRA, are key functions of executive teams in healthcare organizations. Yet decision-makers often base their choices on historical patterns of resource distribution or political pressures. Our aim was to provide leaders with guidance on how to improve PSRA practice, by creating organizational contexts which enable high performance. We carried out in-depth case studies of six Canadian healthcare organizations to obtain from healthcare leaders their understanding of the concept of high performance in PSRA and the factors which contribute to its achievement. Individual and group interviews were carried out (n = 62) with senior managers, middle managers and Board members. Site observations and document review were used to assist researchers in interpreting the interview data. Qualitative data were analyzed iteratively with the literature on empirical examples of PSRA practice, in order to develop a framework of high performance in PSRA. The framework consists of four domains - structures, processes, attitudes and behaviours, and outcomes - within which are 19 specific elements. The emergent themes derive from case studies in different kinds of health organizations (urban/rural, small/large) across Canada. The elements can serve as a checklist for 'high performance' in PSRA. This framework provides a means by which decision-makers in healthcare might assess their practice and identify key areas for improvement. The findings are likely generalizable, certainly within Canada but also across countries. This work constitutes, to our knowledge, the first attempt to present a full package of elements comprising high performance in health care PSRA. PMID- 27367900 TI - Compositional and Structural Versatility in an Unusual Family of anti-Perovskite Fluorides: [Cu(H2O)4]3[(MF6)(M'F6)]. AB - A series of six anti-perovskite fluorides of the type [Cu(H2O)4]3(M1-xM'xF6)2 (where M and M' = V, Cr, Mn, Fe as well as M = Fe and M' = V and Cr) was synthesized as high-quality single crystals via a mild hydrothermal route. These materials belong to a class of perovskite-based structures in which the anions and cations of the regular ABX3 perovskite structure have exchanged positions. Two complex anions, MF6(3-) and M'F6(3-), occupy the normal A and B cation positions, while three complex cations, [Cu(H2O)4](2+), occupy the normally anionic X positions. As in the ABX3 compositions, the A and B positions can be occupied by different complex anions, allowing for the preparation of a wide range of compositions. Magnetic property measurements were performed on all six phases, and complex magnetic behavior was observed at low temperatures in the Mn, Fe, and bimetallic Fe/V and Fe/Cr phases. PMID- 27367902 TI - Comparison of randomization-test procedures for single-case multiple-baseline designs. AB - In three simulation investigations, we examined the statistical properties of several different randomization-test procedures for analyzing the data from single-case multiple-baseline intervention studies. Two procedures (Wampold Worsham and Revusky) are associated with single fixed intervention start points and three are associated with randomly determined intervention start points. Of the latter three, one (Koehler-Levin) is an existing procedure that has been previously examined and the other two (modified Revusky and restricted Marascuilo Busk) are modifications and extensions of existing procedures. All five procedures were found to maintain their Type I error probabilities at acceptable levels. In most of the conditions investigated here, two of the random start point procedures (Koehler-Levin and restricted Marascuilo-Busk) were more powerful than the others with respect to detecting immediate abrupt intervention effects. For designs in which it is not possible to include the same series lengths for all cases, either the modified Revusky or restricted Marascuilo-Busk procedure is recommended. PMID- 27367901 TI - Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in oligodendroglial tumors. AB - Aberrant methylation has been associated with transcriptional inactivation of tumor-related genes in a wide spectrum of human neoplasms. The influence of DNA methylation in oligodendroglial tumors is not fully understood. Genomic DNA was isolated from 61 oligodendroglial tumors for analysis of methylation using methylation-specific multiplex ligation-dependent probe amplification assay (MS MLPA). We correlated methylation status with clinicopathological findings and outcome. The genes found to be most frequently methylated in oligodendroglial tumors were RASSF1A (80.3%), CASP8 (70.5%), and CDKN2A (52.5%). Kaplan-Meier survival curve analysis demonstrated longer duration of progression-free survival in patients with 19q loss, aged less than 38 years, and with a proliferative index of less than 5%. Methylation of the ESR1 promoter is significantly associated with shorter duration of overall survival and progression-free survival, and that methylation of IGSF4 and RASSF1A is significantly associated with shorter duration of progression-free survival. However, none of the methylation status of ESR1, IGSF4, and RASSF1A was of prognostic value for survival in a multivariate Cox model. A number of novel and interesting epigenetic alterations were identified in this study. The findings highlight the importance of methylation profiles in oligodendroglial tumors and their possible involvement in tumorigenesis. PMID- 27367903 TI - Seasonal Changes in Bird Species and Feeding Guilds along Elevational Gradients of the Central Himalayas, Nepal. AB - The Himalayas are a global hotspot for bird diversity with a large number of threatened species, but little is known about seasonal changes in bird communities along elevational gradients in this region. We studied the seasonality of bird diversity in six valleys of the Central Himalayas, Nepal. Using 318 plots with a 50 m radius, located from 2200 to 3800 m a.s.l., and repeated sampling during different seasons (mainly pre-monsoon, monsoon, and post monsoon), we analyzed 3642 occurrences of 178 species. Birds classified in the literature as resident were more species-rich than migratory birds (140 vs. 38 species). In all six valleys and within the studied elevation range, species richness of all birds showed a peak at mid-elevation levels of 2600 or 3000 m a.s.l. Similar patterns were found for the most species-rich feeding guilds of insectivores (96 species) and omnivores (24 species), whereas the species richness of herbivores (37 species including frugivores) increased towards higher elevations. Among these feeding guilds, only species richness of insectivores showed pronounced seasonal changes with higher species numbers during post monsoon season. Similarly, individual bird species showed distinct spatio temporal distribution patterns, with transitions from species dominated by elevational differences to those characterized by strong seasonal changes. In an era of climate change, the results demonstrate that individual bird species as well as feeding guilds might greatly differ in their responses to climate warming and changes in the seasonality of the precipitation regime, two aspects of climate change which should not be analyzed independently. PMID- 27367904 TI - Context-Aware Image Compression. AB - We describe a physics-based data compression method inspired by the photonic time stretch wherein information-rich portions of the data are dilated in a process that emulates the effect of group velocity dispersion on temporal signals. With this coding operation, the data can be downsampled at a lower rate than without it. In contrast to previous implementation of the warped stretch compression, here the decoding can be performed without the need of phase recovery. We present rate-distortion analysis and show improvement in PSNR compared to compression via uniform downsampling. PMID- 27367905 TI - Enteroviral Postencephalitic Parkinsonism With Evidence of Impaired Presynaptic Dopaminergic Function. PMID- 27367906 TI - Transverse relaxation and flip angle mapping: Evaluation of simultaneous and independent methods using multiple spin echoes. AB - PURPOSE: To evaluate transverse relaxation (T2) and flip angle maps derived from signal pathway modeling of multiple spin echoes using simultaneous or independent T2 and flip angle fitting. METHODS: We examined different approaches to indirect and stimulated echo compensated T2 relaxometry from multiple spin echoes to evaluate both T2 and flip angle accuracy in simulation, phantom, and human brain. Signal pathways were modeled with or without independent flip angle maps using either Bloch simulations, or Extended Phase Graph (EPG) with Fourier or Shinnar Le Roux approximation of slice profiles. RESULTS: Slice-selective decay curves differ substantially between models. Inaccurate flip angles are obtained with EPG methods, although T2 values are relatively accurate. Providing measured flip angles to EPG methods yields erroneous T2. Bloch methods improve both T2 and flip angle results. Simultaneous fitting can suffer from flip angle redundancy yielding multiple T2 solutions, particularly in low signal-to-noise ratio cases. CONCLUSION: EPG fitting provides reasonably accurate T2, but is limited by poor accuracy in resulting flip angles, and T2 errors increase when flip angles are provided. Bloch simultaneous fitting of T2 and flip angle provides excellent results, but can be limited by multiple solutions which can be overcome by including a flip angle map. Magn Reson Med 77:2057-2065, 2017. (c) 2016 International Society for MagneticResonance in Medicine. PMID- 27367907 TI - Fenretinide (4-HPR) Targets Caspase-9, ERK 1/2 and the Wnt3a/beta-Catenin Pathway in Medulloblastoma Cells and Medulloblastoma Cell Spheroids. AB - Medulloblastoma (MB), a neuroectodermal tumor arising in the cerebellum, represents the most frequent childhood brain malignancy. Current treatments for MB combine radiation and chemotherapy and are often associated with relevant side effects; novel therapeutic strategies are urgently needed. N-(4-Hydroxyphenyl) retinamide (4-HPR, fenretinide), a synthetic analogue of all-trans retinoic acid, has emerged as a promising and well-tolerated cancer chemopreventive and chemotherapeutic agent for various neoplasms, from breast cancer to neuroblastoma. Here we investigated the effects of 4-HPR on MB cell lines and identified the mechanism of action for a potential use in therapy of MB. Flow cytometry analysis was performed to evaluate 4-HPR induction of apoptosis and oxygen reactive species (ROS) production, as well as cell cycle effects. Functional analysis to determine 4-HPR ability to interfere with MB cell migration and invasion were performed. Western Blot analysis were used to investigate the crucial molecules involved in selected signaling pathways associated with apoptosis (caspase-9 and PARP-1), cell survival (ERK 1/2) and tumor progression (Wnt3a and beta-catenin). We show that 4-HPR induces caspase 9 dependent cell death in DAOY and ONS-76 cells, associated with increased ROS generation, suggesting that free radical intermediates might be directly involved. We observed 4-HPR induction of cell cycle arrest in G1/S phase, inactivated beta-catenin, and inhibition of MB cell migration and invasion. We also evaluated the ability of 4-HPR to target MB cancer-stem/cancer-initiating cells, using an MB spheroids model, followed by flow cytometry and quantitative real-time PCR. 4-HPR treatment reduced DAOY and ONS-76 spheroid formation, in term of number and size. Decreased expression of the surface markers CD133+ and ABCG2+ as well as Oct-4 and Sox-2 gene expression were observed on BTICs treated with 4-HPR further reducing BITIC invasive activities. Finally, we analyzed 4-HPR ability to inhibit MB tumor cell growth in vivo in nude mice. Taken together, our data suggest that 4-HPR targets both parental and MB tumor stem/initiating cell like populations. Since 4-HPR exerts low toxicity, it could represent a valid compound in the treatment of human MB. PMID- 27367908 TI - Occupational Physicians' Reasoning about Recommending Early Return to Work with Work Modifications. AB - Previous research indicates that work modifications can effectively enhance return to work (RTW) at an early stage of work disability. We aimed to examine how occupational physicians (OPs) reason about recommending early return to work (RTW) with work modifications. Pre-defined propositions regarding the use of work modifications in promoting early RTW were discussed in four focus groups with altogether 11 Finnish OPs. Discussions were audio recorded, and the transcribed data were analyzed using qualitative content analysis. Five different rationales for supporting early RTW were identified: to manage medical conditions, to enhance employee well-being, to help workplace stakeholders, to reduce costs to society, and to enhance OP's own professional fulfillment. However, OPs identified situations and conditions in which early RTW may not be suitable. In addition, there were differences between the OPs in the interpretation of the rationales, suggesting variation in clinical practice. In conclusion, encouraging early RTW with work modifications was perceived by OPs as a meaningful task and, to a large extent, beneficial for employees and several stakeholders. However, this practice was not accepted without consideration to the RTW situation and context. If early RTW and work modifications are to be promoted, OPs should be offered education that addresses their views regarding this practice. PMID- 27367909 TI - Molecular Detection of Methicillin-Resistant Staphylococcus aureus by Non-Protein Coding RNA-Mediated Monoplex Polymerase Chain Reaction. AB - Non-protein coding RNA (npcRNA) is a functional RNA molecule that is not translated into a protein. Bacterial npcRNAs are structurally diversified molecules, typically 50-200 nucleotides in length. They play a crucial physiological role in cellular networking, including stress responses, replication and bacterial virulence. In this study, by using an identified npcRNA gene (Sau-02) in Methicillin-resistant Staphylococcus aureus (MRSA), we identified the Gram-positive bacteria S. aureus. A Sau-02-mediated monoplex Polymerase Chain Reaction (PCR) assay was designed that displayed high sensitivity and specificity. Fourteen different bacteria and 18 S. aureus strains were tested, and the results showed that the Sau-02 gene is specific to S. aureus. The detection limit was tested against genomic DNA from MRSA and was found to be ~10 genome copies. Further, the detection was extended to whole-cell MRSA detection, and we reached the detection limit with two bacteria. The monoplex PCR assay demonstrated in this study is a novel detection method that can replicate other npcRNA-mediated detection assays. PMID- 27367910 TI - Therapeutic angiogenesis by vascular endothelial growth factor supplementation for treatment of renal disease. AB - PURPOSE OF REVIEW: Vascular endothelial growth factors (VEGFs) influence renal function through angiogenesis, with VEGF-A being the most potent inducer of vascular formation. In the normal glomerulus, tight homeostatic balance is maintained between the levels of VEGF-A isoforms produced by podocyte cells, and the VEGF receptors (VEGFRs) expressed by glomerular endothelial, mesangial, and podocyte cells. Renal disease occurs when this homeostatic balance is lost, manifesting in the abnormal autocrine and paracrine VEGF-A/VEGFR signaling, ultrastructural glomerular and tubular damage, and impaired filtration. RECENT FINDINGS: Preclinical disease models of ischemic renal injury, including acute ischemia/reperfusion, thrombotic microangiopathy, and chronic renovascular disease, treated with exogenous VEGF supplementation demonstrated therapeutic efficacy. These results suggest a therapeutic VEGF-A paracrine effect on endothelial cells in the context of acute or chronic obstructive ischemia. Conversely, renal dysfunction in diabetic nephropathy appears to occur through an upregulated VEGF autocrine effect on podocyte cells, which is exacerbated by hyperglycemia. Therefore, VEGF supplementation therapy may be contraindicated for treatment of diabetic nephropathy, but specific results will depend on dose and on the specific site of VEGF delivery. A drug delivery system that demonstrates cell specificity for glomerular or peritubular capillaries could be employed to restore balance to VEGF-A/VEGFR2 signaling, and by doing so, prevent the progression to end-stage renal disease. SUMMARY: The review discusses the preclinical data available for VEGF supplementation therapy in models of renal disease. PMID- 27367912 TI - Cannabinoid receptors in the kidney. AB - PURPOSE OF REVIEW: The endocannabinoid system modulates cell signaling targets that are essential for energy homeostasis. Endocannabinoids bind to G protein coupled receptors in the central nervous system and periphery, including the kidney. Modulation of cannabinoid receptor 1 (CB1) and CB2 activity in the kidney in diabetes and obesity has been identified as potential therapeutic target to reduce albuminuria and renal fibrosis. This review will highlight the results of recent studies that have identified a role for CB1 and CB2 in normal and pathological renal conditions. RECENT FINDINGS: CB1 and CB2 have been reported to play key roles in renal function and dysfunction. Recent studies have determined that antagonism of CB1 and agonism of CB2 in diabetic nephropathy and obesity associated kidney disease can reduce albuminuria, potentially by acting on both the glomeruli and tubules. Emerging studies have also identified a role for CB1 in renal diseases associated with fibrosis, with CB1 upregulated in multiple models of human nephropathies. SUMMARY: Emerging studies using isolated cells, rodent models, and human studies have identified a critical role for the endocannabinoid system in renal function and disease. Thus, therapeutics that modulate the activity of CB1 and CB2 in renal disease could become clinically relevant. PMID- 27367911 TI - Urea transport and clinical potential of urearetics. AB - PURPOSE OF REVIEW: Urea is transported by urea transporter proteins in kidney, erythrocytes, and other tissues. Mice in which different urea transporters have been knocked out have urine-concentrating defects, which has led to the development and testing of urea transporters Slc14A2 (UT-A) and Slc14A1 (UT-B) inhibitors as urearetics. This review summarizes the knowledge gained during the past year on urea transporter regulation and investigations into the clinical potential of urearetics. RECENT FINDINGS: UT-A1 undergoes several posttranslational modifications that increase its function by increasing UT-A1 accumulation in the apical plasma membrane. UT-A1 is phosphorylated by protein kinase A, exchange protein activated by cyclic AMP, protein kinase Calpha, and AMP-activated protein kinase, all at different serine residues. UT-A1 is also regulated by 14-3-3, which contributes to UT-A1 removal from the membrane. UT-A1 is glycosylated with various glycan moieties in animal models of diabetes mellitus. Transgenic expression of UT-A1 into UT-A1/UT-A3 knockout mice restores urine-concentrating ability. UT-B is present in descending vasa recta and urinary bladder, and is linked to bladder cancer. Inhibitors of UT-A and UT-B have been developed that result in diuresis with fewer abnormalities in serum electrolytes than conventional diuretics. SUMMARY: Urea transporters play critical roles in the urine-concentrating mechanism. Urea transport inhibitors are a promising new class of diuretic agent. PMID- 27367913 TI - Angiotensin converting enzyme 2 and diminazene: role in cardiovascular and blood pressure regulation. AB - PURPOSE OF REVIEW: Angiotensin converting enzyme 2 (ACE2) is an important regulator of the renin-angiotensin system through actions to degrade angiotensin II. Loss of ACE2 can contribute to the development and progression of cardiovascular disease, and experimental studies have highlighted a beneficial role for novel therapeutic approaches that activate or replenish tissue ACE2. This review focuses on experimental studies that have used the off-target effects of the antitrypanosomal agent, diminazene aceturate (DIZE) to activate ACE2. RECENT FINDINGS: In cardiovascular disease, activation of the classical renin angiotensin system and depletion of ACE2 leads to pathophysiological changes. One approach to activate ACE2 involves the drug DIZE, which has been shown to have beneficial effects in experimental models of hypertension, pulmonary hypertension, myocardial infarction, stroke, atherosclerosis, type 1 diabetes, and eye disease. The precise mechanism of action of DIZE to activate ACE2 remains under scrutiny. SUMMARY: Activation of ACE2 may represent an important therapeutic approach in cardiovascular disease. To date, most studies have focused on the off-target actions of DIZE, in experimental models of disease. More research is required to determine the exact mechanism of action of DIZE and evaluate its therapeutic potential in comparison with currently available clinical interventions. There are no clinical studies of DIZE, and its side effects, and toxicity make such studies unlikely. Hence, new methods of selectively activating or replenishing ACE2 will be needed in the future if this approach is to be used in a clinical context. PMID- 27367914 TI - Recent advances in understanding renal ammonia metabolism and transport. AB - PURPOSE OF REVIEW: The purpose of this review is to provide a succinct description of the recent findings that advance our understanding of the fundamental renal process of ammonia metabolism and transport in conditions relevant to the clinician. RECENT FINDINGS: Recent studies advance our understanding of renal ammonia metabolism. Mechanisms through which chronic kidney disease and altered dietary protein intake alter ammonia excretion have been identified. Lithium, although it can acutely cause distal renal tubular acidosis, was shown with long-term use to increase urinary ammonia excretion, and this appeared to be mediated, at least in part, by increased Rhcg expression. Gene deletion studies showed that the ammonia recycling enzyme, glutamine synthetase, has a critical role in normal-stimulated and acidosis-stimulated ammonia metabolism and that the proximal tubule basolateral bicarbonate transporter, NBCe1, is necessary for normal ammonia metabolism. Finally, our understanding of the molecular ammonia species, NH3 versus NH4, transported by Rh glycoproteins continues to be advanced. SUMMARY: Fundamental studies have been recently published that advance our understanding of the regulation of ammonia metabolism in clinically important circumstances, and our understanding of the mechanisms and regulation of proximal tubule ammonia generation, and the mechanisms through which Rh glycoproteins contribute to ammonia secretion. PMID- 27367915 TI - A case study of the introduction of the International Classification for Nursing Practice((r)) in Poland. AB - INTRODUCTION: The development of a nursing practice, improvements in nurses' autonomy, and increased professional and personal responsibility for the medical services provided all require professional documentation with records of health status assessments, decisions undertaken, actions and their outcomes for each patient. The International Classification for Nursing Practice is a tool that meets all of these needs, and although it requires continuous evaluation, it offers professional documentation and communication in the practitioner and researcher community. AIM: The aim of this paper is to present a theoretical critique of an issue related to policy and experience of the current situation in Polish nursing - especially of the efforts to standardize nursing practices through the introduction and development of the Classification in Poland. DISCUSSION: Despite extensive promotion and training by International Council of Nurses members worldwide, there are still many countries where the Classification has not been implemented as a standard tool in healthcare facilities. Recently, a number of initiatives were undertaken in cooperation with the local and state authorities to disseminate the Classification in healthcare facilities. CONCLUSIONS: Thanks to intense efforts by the Polish Nurses Association and the International Council of Nurses Accredited Center for ICNP((r)) Research & Development at the Medical University of Lodz, the Classification is known in Poland and has been tested at several centres. Nevertheless, an actual implementation that would allow for national and international interoperability requires strategic governmental decisions and close cooperation with information technology companies operating in the country. IMPLICATIONS FOR NURSING & HEALTH POLICY: Discussing the barriers to the implementation of the Classification can improve understanding of it and its use. At a policy level, decision makers need to understand that use Classification in eHealth services and tools it is necessary to achieve interoperability. PMID- 27367917 TI - Bilateral Thyroarytenoid Botulinum Toxin Type A Injection for the Treatment of Refractory Chronic Cough. AB - IMPORTANCE: Refractory chronic cough is a debilitating condition with limited therapeutic options. Laryngeal botulinum toxin type A (BtxA) has been anecdotally reported to benefit patients with chronic cough. We report on our experience with the use of BtxA for the treatment of patients with refractory chronic cough. OBJECTIVE: To describe the effects of electromyography (EMG)-guided thyroarytenoid (TA) BtxA injection for the treatment of refractory chronic cough. DESIGN, SETTING, AND PARTICIPANTS: For this single tertiary referral center retrospective case series, we included all patients with refractory chronic cough who received bilateral EMG-guided TA BtxA injections (n = 22) between July 1, 2013, and July 31, 2014, at the Mayo Clinic in Rochester, Minnesota. INTERVENTION: Bilateral TA BtxA injection. MAIN OUTCOMES AND MEASURES: The primary outcome is a self-reported improvement of 50% or more in cough severity and/or symptoms by a 2-month follow-up telephone call. Adverse events and patient reported quality measures were also assessed. RESULTS: A total of 22 patients (median [interquartile range] age 61 [57.5-85] years; 19 of 22 women) underwent 31 distinct laryngeal BtxA treatment sessions. The primary outcome of self reported improvement of 50% or more of cough severity and/or symptoms was achieved in 16 of 31 (52%) treatment sessions. Eleven patients (50%) reported greater than 50% improvement after the first BtxA injection. No major complications occurred. Postprocedural liquid dysphagia had a positive predictive value of 84% and negative predictive value of 100% for response to therapy. CONCLUSIONS AND RELEVANCE: In this case series, laryngeal BtxA injection was well tolerated in patients with refractory chronic cough with half of participants experiencing at least short-term improvement in their cough. The occurrence of liquid dysphagia after a BtxA injection appeared to be predictive of a beneficial response. The durability of response, patient selection criteria, and optimal BtxA dosage remains to be determined. PMID- 27367916 TI - Effects of acute static, ballistic, and PNF stretching exercise on the muscle and tendon tissue properties. AB - The purpose of this study was to investigate the influence of a single static, ballistic, or proprioceptive neuromuscular facilitation (PNF) stretching exercise on the various muscle-tendon parameters of the lower leg and to detect possible differences in the effects between the methods. Volunteers (n = 122) were randomly divided into static, ballistic, and PNF stretching groups and a control group. Before and after the 4 * 30 s stretching intervention, we determined the maximum dorsiflexion range of motion (RoM) with the corresponding fascicle length and pennation angle of the gastrocnemius medialis. Passive resistive torque (PRT) and maximum voluntary contraction (MVC) were measured with a dynamometer. Observation of muscle-tendon junction (MTJ) displacement with ultrasound allowed us to determine the length changes in the tendon and muscle, respectively, and hence to calculate stiffness. Although RoM increased (static: +4.3%, ballistic: +4.5%, PNF: +3.5%), PRT (static: -11.4%, ballistic: -11.5%, PNF: -13,7%), muscle stiffness (static: -13.1%, ballistic: -20.3%, PNF: -20.2%), and muscle-tendon stiffness (static: -11.3%, ballistic: -10.5%, PNF: -13.7%) decreased significantly in all the stretching groups. Only in the PNF stretching group, the pennation angle in the stretched position (-4.2%) and plantar flexor MVC (-4.6%) decreased significantly. Multivariate analysis showed no clinically relevant difference between the stretching groups. The increase in RoM and the decrease in PRT and muscle-tendon stiffness could be explained by more compliant muscle tissue following a single static, ballistic, or PNF stretching exercise. PMID- 27367918 TI - Static magnetic field enhances the viability and proliferation rate of adipose tissue-derived mesenchymal stem cells potentially through activation of the phosphoinositide 3-kinase/Akt (PI3K/Akt) pathway. AB - The aim of this work was to investigate the effects of 0.5T static magnetic field (sMF) on the viability and proliferation rate of human adipose-derived mesenchymal stromal stem cells (hASCs) via activation of the phosphoinositide 3 kinase/Akt (PI3K/Akt) signaling pathway. In a 7-d culture we examined cell growth kinetic and population doubling time (PDT). We also examined cell morphology and the cellular senescence markers level. Exposure to sMF enhanced the viability of these cells. However, the effect was blocked by treating the cells with LY294002, a P13K inhibitor. We compared this effect by Western Blot analysis of Akt protein expression. We also examined whether the cell response on sMF stimulation is dependent on integrin engagement and we measured integrin gene expression. Our results suggest that stimulation using sMF is a viable method to improve hASC viability. sMF is involved in mechanisms associated with controlling cell proliferative potential signaling events. PMID- 27367919 TI - Melatonin and neurotrophins NT-3, BDNF, NGF in patients with varying levels of depression severity. AB - BACKGROUND: Disrupted circadian rhythm of melatonin secretion in depression shows a relationship with the exacerbation of inflammatory processes. Proinflammatory mechanisms of depression are sustained by oxidative stress. This contributes to melatonin deficiency and to the malfunction of the defense mechanisms in the brain. Disrupted melatonin secretion in depression may have an influence on the concentrations of neurotrophic factors (NF), such as neurotrophin-3 (NT-3), brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Disturbance in neurotrophin release may affect synaptic plasticity and cause exacerbation of neurodegenerative processes in the central nervous system. The aim of this study was to assess the concentrations of melatonin and NF of the brain in patients with varying levels of depression severity. METHOD: 160 males and females were enrolled in the study, 120 of whom were diagnosed with various types of depression. The control group comprised 40 healthy individuals. At 3:00a.m. all patients had salivary melatonin concentrations determined utilizing a competitive enzyme immunoassay technique (ELISA). In addition, at 7:00a.m. all patients had serum neurotrophin (NT-3, BDNF, NGF) concentrations determined by means of ELISA. RESULTS: The highest melatonin secretion was observed at 3:00a.m. in severely depressed females. In the groups with mild and moderate depression, melatonin secretion at 3:00a.m. was comparable between males and females. In addition, a decrease in the concentrations of neurotrophins was revealed in patients at all levels of depression severity. CONCLUSION: Melatonin may be a significant marker of depression severity. Melatonin and NF in depressed patients show neuroprotective effects. PMID- 27367920 TI - Protective Effects of alpha-Boswellic Acids in a Pulmonary Arterial Hypertensive Rat Model. AB - The purpose of this study was to observe the protective effects of alpha boswellic acids on hypoxia-induced pulmonary vascular structural remodeling in pulmonary arterial smooth muscle cells in a hypertensive rat model. Pulmonary arterial smooth muscle cells were cultured and then randomly divided into four groups: normoxia, hypoxia (3 % O2; 24 h), hypoxia plus alpha-boswellic acids, and hypoxia plus DMSO (as a positive control), according to the different concentrations of alpha-boswellic acids (21.90 uM, 43.79 uM, and 87.58 uM). Apoptosis and proliferation of pulmonary arterial smooth muscle cells significantly decreased in the hypoxia plus alpha-boswellic acids group compared with the hypoxia and hypoxia plus DMSO groups (n = 8, p < 0.05). The mRNA and protein phosphorylation levels of c-Jun N-terminal kinase 1 and extracellular regulated protein kinase 1 were significantly elevated in hypoxic cells compared with normal cells. However, the mRNA and protein phosphorylation levels of c-Jun N-terminal kinase 1 and extracellular regulated protein kinase 1 markedly decreased in the hypoxia plus alpha-boswellic acids group compared with the hypoxia plus DMSO group (n = 8, p < 0.05; n = 13, p < 0.05, respectively). Our findings suggest that alpha-boswellic acids can inhibit inappropriate apoptosis and excessive proliferation of pulmonary arterial smooth muscle cells and pulmonary vascular remodeling by repressing the expression of c-Jun N-terminal kinase 1 and extracellular regulated protein kinase 1 under hypoxic conditions. PMID- 27367922 TI - Does Continuous Electronic ST-Segment Monitoring Enhance Prediction of Postoperative Troponin Elevation? PMID- 27367921 TI - Fluocinolone Acetonide Intravitreal Implant in the Visual Axis. PMID- 27367923 TI - Examining the "Halo Effect" of Surgical Care Within Health Systems. PMID- 27367924 TI - Mean Platelet Volume is Associated with Diabetic Macular Edema in Patients with Type-2 Diabetes Mellitus. AB - AIM: To evaluate the effect of the platelet indices on the stage of diabetic retinopathy (DR) and diabetic macular edema (DME). METHODS: In this retrospective study, the mean platelet valume (MPV), Plateletcrit (PCT), platelet (PLT), and platelet distribution width (PDW) of 199 diabetic patients and 76 healthy subjects were enrolled. The participants were divided into four groups. The first group was healthy control; the second group consisted of diabetic patients without DR; the third group was nonproliferative DR (NPDR); and the fourth group was proliferative DR (PDR). RESULTS: Significant differences were found only in MPV and PCT values between patients with diabetes and healthy participants (8.6+/ 0.96 fL vs 8.32+/-0.9 fL, P=0.011, 0.216+/- 0.58 vs 0.202+/-0.52, P=0.038). Comparing the groups, a statistically significant difference in MPV values was found between groups 4 and 1 (8.91+/-.7 fL vs 8.32+/-0.9 fL P=0.001) and between groups 4 and 3 (8.91+/-.7 fL vs 8.42+/-0.9 fL P=0.014). The MPV values of patients with DME were significantly higher than those of diabetic patients without DME (8.87+/-0.80 fL vs 8.45+/-0.97 fL). CONCLUSION: High MPV values may be an important risk factor for the development of PDR and DME in patients with diabetic retinopathy. PMID- 27367925 TI - Change Your Ways: Fostering Health Attitudes Toward Change Through Selective Exposure to Online Health Messages. AB - Health information is often sought online, despite varying credibility of online sources, and may shape health behaviors. This investigation builds on the Selective Exposure Self- and Affect-Management model to examine selective exposure to online health information from low- and high-credibility sources and subsequent effects on attitudes toward health behaviors. In a lab study, 419 participants accessed online search results about health topics. The display varied messages in a 4 * 2 * 2 all within-subjects design, with topic as a four step factor (organic food, coffee, fruit and vegetable consumption, physical exercise) and source credibility (low vs. high) and issue stance (promoting vs. opposing health behavior) as two-step factors. Displayed messages either promoted or opposed the related behavior. Results showed that perceiving greater standard behavior discrepancy (between recommended behavior standards and own behavior) fostered behavior-related attitudes through selective exposure to messages promoting that behavior. The effects from selective exposure to health messages on attitudes occurred regardless of associated source credibility. PMID- 27367926 TI - Influence of Speed and Rainfall on Large-Scale Wheat Lodging from 2007 to 2014 in China. AB - Strong wind and heavy rain remain the two most important causes of large acreage wheat (Triticum aestivum L.) lodging in China. For research the influence of wind speed and rainfall-separately as well as together-on the extent and degree of lodging, five levels of the severity of lodging were defined based on a combination of the lodging area and the degree of tilting. Detailed meteorological information was studied on 52 instances of large-scale lodging that occurred from 2007 to 2014. The results showed that strong wind's lodging accounted for 8% of the instances studied, continuous rainfall's lodging accounted for 19% and strong winds-heavy rainfall's accounted for 73%. The minimum instantaneous wind speed that could cause large-scale lodging was closely related to rainfall. Without rainfall, the wind speed that resulted in lodging ranging in severity from slight to severe (Level 2 to Level 5) was 14.9 m/s, 19.3 m/s, 21.5 m/s, and 26.5 m/s, respectively; when accompanied by rainfall, the wind speed that resulted in lodging of the same severity decreased linearly with the increase of rainfall. These results will be particularly useful in preventing and alleviating wheat lodging as well screening wheat varieties with good lodging resistance. PMID- 27367927 TI - Association Between Religious Service Attendance and Lower Suicide Rates Among US Women. AB - IMPORTANCE: Previous studies have linked suicide risk with religious participation, but the majority have used ecologic, cross-sectional, or case control data. OBJECTIVE: To examine the longitudinal association between religious service attendance and suicide and the joint associations of suicide with service attendance and religious affiliation. DESIGN, SETTING, AND PARTICIPANTS: We evaluated associations between religious service attendance and suicide from 1996 through June 2010 in a large, long-term prospective cohort, the Nurses' Health Study, in an analysis that included 89 708 women. Religious service attendance was self-reported in 1992 and 1996. Data analysis was conducted from 1996 through 2010. MAIN OUTCOMES AND MEASURES: Cox proportional hazards regression models were used to examine the association between religious service attendance and suicide, adjusting for demographic covariates, lifestyle factors, medical history, depressive symptoms, and social integration measures. We performed sensitivity analyses to examine the influence of unmeasured confounding. RESULTS: Among 89 708 women aged 30 to 55 years who participated in the Nurses' Health Study, attendance at religious services once per week or more was associated with an approximately 5-fold lower rate of suicide compared with never attending religious services (hazard ratio, 0.16; 95% CI, 0.06-0.46). Service attendance once or more per week vs less frequent attendance was associated with a hazard ratio of 0.05 (95% CI, 0.006-0.48) for Catholics but only 0.34 (95% CI, 0.10-1.10) for Protestants (P = .05 for heterogeneity). Results were robust in sensitivity analysis and to exclusions of persons who were previously depressed or had a history of cancer or cardiovascular disease. There was evidence that social integration, depressive symptoms, and alcohol consumption partially mediated the association among those occasionally attending services, but not for those attending frequently. CONCLUSIONS AND RELEVANCE: In this cohort of US women, frequent religious service attendance was associated with a significantly lower rate of suicide. PMID- 27367928 TI - Protein folding on biosensor tips: folding of maltodextrin glucosidase monitored by its interactions with GroEL. AB - Protein folding has been extensively studied for the past six decades by employing solution-based methods such as solubility, enzymatic activity, secondary structure analysis, and analytical methods like FRET, NMR, and HD exchange. However, for rapid analysis of the folding process, solution-based approaches are often plagued with aggregation side reactions resulting in poor yields. In this work, we demonstrate that a bio-layer interferometry (BLI) chaperonin detection system can identify superior refolding conditions for denatured proteins. The degree of immobilized protein folding as a function of time can be detected by monitoring the binding of the high-affinity nucleotide free form of the chaperonin GroEL. GroEL preferentially interacts with proteins that have hydrophobic surfaces exposed in their unfolded or partially folded form, so a decrease in GroEL binding can be correlated with burial of hydrophobic surfaces as folding progresses. The magnitude of GroEL binding to the protein immobilized on bio-layer interferometry biosensor inversely reflects the extent of protein folding and hydrophobic residue burial. We demonstrate conditions where accelerated folding can be observed for the aggregation-prone protein maltodextrin glucosidase (MalZ). Superior immobilized folding conditions identified on the bio-layer interferometry biosensor surface were reproduced on Ni-NTA sepharose bead surfaces and resulted in significant improvement in folding yields of released MalZ (measured by enzymatic activity) compared to bulk refolding conditions in solution. PMID- 27367929 TI - DRD4, Income, and Children's Food Choices: Plasticity Allele or Different Opportunities?-Reply. PMID- 27367930 TI - A phenomenologic investigation of pediatric residents' experiences being parented and giving parenting advice. AB - Factors surrounding pediatricians' parenting advice and training on parenting during residency have not been well studied. The primary purpose of this study was to examine pediatric residents' self-reported experiences giving parenting advice and explore the relationship between parenting advice given and types of parenting residents received as children. Thirteen OUHSC pediatric residents were individually interviewed to examine experiences being parented and giving parenting advice. Phenomenological methods were used to explicate themes and secondary analyses explored relationships of findings based upon Baumrind's parenting styles (authoritative, authoritarian, permissive). While childhood experiences were not specifically correlated to the parenting advice style of pediatric residents interviewed, virtually all reported relying upon childhood experiences to generate their advice. Those describing authoritative parents reported giving more authoritative advice while others reported more variable advice. Core interview themes related to residents' parenting advice included anxiety about not being a parent, varying advice based on families' needs, and emphasis of positive interactions and consistency. Themes related to how residents were parented included discipline being a learning process for their parents and recalling that their parents always had expectations, yet always loved them. Pediatric residents interviewed reported giving family centered parenting advice with elements of positive interactions and consistency, but interviews highlighted many areas of apprehension residents have around giving parenting advice. Our study suggests that pediatric residents may benefit from more general educational opportunities to develop the content of their parenting advice, including reflecting on any impact from their own upbringing. PMID- 27367931 TI - The association between passive and active tobacco smoke exposure and child weight status among Spanish children. AB - OBJECTIVE: To assess the impact of passive and active tobacco smoke exposure, both pre- and postnatally, on child body mass index (BMI) and overweight. METHODS: Pregnant women were enrolled into the Spanish INMA prospective birth cohort during 1997 to 2008. Tobacco smoke exposure was assessed by questionnaire and corroborated by pre- and postnatal cotinine measurements. Children were followed up until 4 years in newer subcohorts (N = 1866) and until 14 years in one older subcohort (N = 427). Child age- and sex-specific BMI Z-scores were calculated, and generalized estimating equations were used to model their relationship with repeated measures of tobacco smoke exposure. RESULTS: Associations between prenatal passive exposure to tobacco smoke (adjusted beta = 0.15, 95% CI: 0.05-0.25) and active maternal smoking (adjusted beta = 0.20, 95% CI: 0.08-0.33) and child zBMI up to 4 years were observed. Stronger associations were observed in the older subcohort between both prenatal and child passive smoke exposure and zBMI up to 14 years. CONCLUSIONS: Evidence for an effect of both passive and maternal active smoking on child postnatal growth has been provided. Although residual confounding cannot be completely ruled out, associations were robust to adjustment for a range of lifestyle factors. PMID- 27367932 TI - Out-of-Pocket Spending for Hospitalizations Among Nonelderly Adults. AB - IMPORTANCE: Patients' out-of-pocket spending for major health care expenses, such as inpatient care, may result in substantial financial distress. Limited contemporary data exist on out-of-pocket spending among nonelderly adults. OBJECTIVES: To evaluate out-of-pocket spending associated with hospitalizations and to assess how this spending varied over time and by patient characteristics, region, and type of insurance. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of medical claims for 7.3 million hospitalizations using 2009-2013 data from Aetna, UnitedHealthcare, and Humana insurance companies representing approximately 50 million members was performed. Out-of-pocket spending was evaluated by age, sex, type of insurance, region, and principal diagnosis or procedure for hospitalized adults aged 18 to 64 years who were enrolled in employer-sponsored and individual-market health insurance plans from January 1, 2009, to December 31, 2013. The study was conducted between July 1, 2015, and March 1, 2016. MAIN OUTCOMES AND MEASURES: Primary outcomes were total out-of pocket spending and spending attributed to deductibles, copayments, and coinsurance for all hospitalizations. Other outcomes included out-of-pocket spending associated with 7 commonly occurring inpatient diagnoses and procedures: acute myocardial infarction, live birth, pneumonia, appendicitis, coronary artery bypass graft, total knee arthroplasty, and spinal fusion. RESULTS: From 2009 to 2013, total cost sharing per inpatient hospitalization increased by 37%, from $738 in 2009 (95% CI, $736-$740) to $1013 in 2013 (95% CI, $1011-$1016), after adjusting for inflation and case-mix differences. This rise was driven primarily by increases in the amount applied to deductibles, which grew by 86% from $145 in 2009 (95% CI, $144-$146) to $270 in 2013 (95% CI, $269-$271), and by increases in coinsurance, which grew by 33% over the study period from $518 in 2009 (95% CI, $516-$520) to $688 in 2013 (95% CI, $686-$690). In 2013, total cost sharing was highest for enrollees in individual market plans ($1875 per hospitalization; 95% CI, $1867-$1883) and consumer-directed health plans ($1219; 95% CI, $1216-$1223). Cost sharing varied substantially across regions, diagnoses, and procedures. CONCLUSIONS AND RELEVANCE: Mean out-of-pocket spending among commercially insured adults exceeded $1000 per inpatient hospitalization in 2013. Wide variability in out-of-pocket spending merits greater attention from policymakers. PMID- 27367933 TI - The CD25-binding antibody Daclizumab High-Yield Process has a distinct glycosylation pattern and reduced antibody-dependent cell-mediated cytotoxicity in comparison to Zenapax(r). AB - The CD25-binding antibody daclizumab high-yield process (DAC HYP) is an interleukin (IL)-2 signal modulating antibody that shares primary amino acid sequence and CD25 binding affinity with Zenapax(r), a distinct form of daclizumab, which was approved for the prevention of acute organ rejection in patients receiving renal transplants as part of an immunosuppressive regimen that includes cyclosporine and corticosteroids. Comparison of the physicochemical properties of the two antibody forms revealed the glycosylation profile of DAC HYP differs from Zenapax in both glycan distribution and the types of oligosaccharides, most notably high-mannose, galactosylated and galactose-alpha 1,3-galactose (alpha-Gal) oligosaccharides, resulting in a DAC HYP antibody material that is structurally distinct from Zenapax. Although neither antibody elicited complement-dependent cytotoxicity in vitro, DAC HYP antibody had significantly reduced levels of antibody-dependent cell-mediated cytotoxicity (ADCC). The ADCC activity required natural killer (NK) cells, but not monocytes, suggesting the effects were mediated through binding to Fc-gamma RIII (CD16). Incubation of each antibody with peripheral blood mononuclear cells also caused the down-modulation of CD16 expression on NK cells and the CD16 down-modulation was greater for Zenapax in comparison to that observed for DAC HYP. The substantive glycosylation differences between the two antibody forms and corresponding greater Fc-mediated effector activities by Zenapax, including cell killing activity, manifest as a difference in the biological function and pharmacology between DAC HYP and Zenapax. PMID- 27367934 TI - Preparation of Surfactant-Resistant Polymersomes with Ultrathick Membranes through RAFT Dispersion Polymerization. AB - Surfactant-resistant polymersomes have substantial potential to be used as delivery vehicles in industrial applications. Herein, we report the preparation of poly(ethylene oxide)-block-polystyrene copolymers with ultrahigh hydrophobic block molecular weights through RAFT dispersion polymerization, which allows the polymerization-induced self-assembly into well-defined polymersomes with ultrathick membranes up to ~47 nm. These ultrathick membranes significantly enhance the resistance against surfactant solubilization of the vesicles, improving the vesicles' potential for use in industrial encapsulations. Vesicle encapsulated actives are well retained in the presence of up to 40 wt % of various anionic and nonionic surfactants, with less than 7% active leakage being observed after 30 days. PMID- 27367935 TI - Epigenetics and cardiovascular risk in childhood. AB - Cardiovascular disease (CVD) can arise at the early stages of development and growth. Genetic and environmental factors may interact resulting in epigenetic modifications with abnormal phenotypic expression of genetic information without any change in the nucleotide sequence of DNA. Maternal dietary imbalance, inadequate to meet the nutritional needs of the fetus can lead to intrauterine growth retardation, decreased gestational age, low birth weight, excessive post natal growth and metabolic alterations, with subsequent appearance of CVD risk factors. Fetal exposure to high cholesterol, diabetes and maternal obesity is associated with increased risk and progression of atherosclerosis. Maternal smoking during pregnancy and exposure to various environmental pollutants induce epigenetic alterations of gene expression relevant to the onset or progression of CVD. In children with hypercholesterolemia and/or obesity, oxidative stress activates platelets and monocytes, which release proinflammatory and proatherogenic substances, inducing endothelial dysfunction, decreased Doppler flow-mediated dilation and increased carotid intima-media thickness. Primary prevention of atherosclerosis should be implemented early. It is necessary to identify, through screening, high-risk apparently healthy children and take care of them enforcing healthy lifestyle (mainly consisting of Mediterranean diet and physical activity), prescribing nutraceuticals and eventual medications, if required by a high-risk profile. The key issue is the restoration of endothelial function in the reversible stage of atherosclerosis. Epigenetics may provide new markers for an early identification of children at risk and thereby develop innovative therapies and specific nutritional interventions in critical times. PMID- 27367936 TI - Agreement between activPAL3c accelerometers placed at different thigh positions. AB - ActivPAL3c triaxial accelerometers are increasingly used to assess physical activity and sedentary behaviours. However, little is known how attachment site (left vs. right or upper vs. lower thigh) affects activPAL3c accelerometer outcomes. Twenty-eight adults wore four activPAL3c accelerometers attached 2cm above and below the midpoint of the left and right thigh during five minutes of laboratory-based walking at a self-selected pace, treadmill walking at 0.89 and 1.56m/s, and treadmill running at 2.22m/s, and during approximately seven hours of free-living conditions. One-way ANOVA revealed no statistically significant differences in accelerometer output between ActivPAL3c accelerometers at these locations during both laboratory-based, and free-living conditions. Intraclass correlation coefficients showed a high level of agreement between activPAL3c accelerometers during laboratory and free living activities (ICC(2,1) 0.76-1.00). The attachment sites used in this study do not appear to significantly influence outcomes for step count, sitting or walking time, or number of postural transitions from triaxial activPAL3c accelerometers during laboratory-based walking or free-living conditions. Therefore if necessary, to enhance participant compliance during monitoring periods, these sites could be used interchangeably. Studies of longer duration incorporating additional laboratory and recreational activities are needed to confirm these findings. PMID- 27367937 TI - Required coefficient of friction during level walking is predictive of slipping. AB - The required coefficient of friction (RCOF) is frequently reported in the literature as an indicator of slip propensity. This study aimed to further develop slip prediction models based on RCOF by examining slips under moderately slippery conditions where the RCOF was approximately equal to the available coefficient of friction. Baseline RCOFs were found for normal walking trials and then an unexpected slip was introduced with a moderately slippery boot-floor contaminant combination for thirty-one subjects. Slip outcomes (i.e., whether a subject experienced a slip) were assessed based on the displacement of a marker placed on the heel. A logistic regression analysis was used to model the impact of RCOF on slipping. Results showed that subjects who walked with a greater RCOF were found to have a higher probability of slipping. The predicted probability of a slip across the RCOF ranged from 3% to 95% and an increase of 0.01 in RCOF was associated with a slipping odds ratio of 1.7. Thus, modest differences in RCOF can have a dramatic impact on slip propensity. This study shows that RCOF can be a sensitive and valid predictor of slipping in realistic frictional environments. PMID- 27367938 TI - Spontaneous cerebrospinal fluid leak from an anomalous thoracic nerve root: case report. AB - The authors report the case of a 28-year-old woman with a spontaneous cerebrospinal fluid leak from the sleeve of a redundant thoracic nerve root. She presented with postural headaches and orthostatic symptoms indicative of intracranial hypotension. CT myelography revealed that the lesion was located at the T-11 nerve root. After failure of conservative management, including blood patches and thrombin glue injections, the patient was successfully treated with surgical decompression and ligation of the duplicate nerve, resulting in full resolution of her orthostatic symptoms. PMID- 27367939 TI - Three-dimensional models: an emerging investigational revolution for craniovertebral junction surgery. AB - Complex craniovertebral junctional anomalies can be daunting to treat surgically, and preoperative information regarding the osseous abnormalities, course of the vertebral arteries, size of the pedicles, and location of the transverse foramina is invaluable to surgeons operating on these challenging cases. The authors present their experience with the emerging technology of 3D model acquisition for surgery in 11 cases of complex craniovertebral junction region anomalies. For each case, a 3D printed model was made from thin CT scans using a 64-slice CT scanner. The inclination of the joints, the presence of false articulations, the size of the pedicles, and the course of the vertebral arteries were studied preoperatively on the 3D models. The sizes of the plates and screws to be used and the angle of insertion of the screws were calculated based on the data from the models. The model was scaled to actual size and was kept beside the operating surgeon in its anatomical position during surgery. The potential uses of the models and their advantages over conventional radiological investigations are discussed. The authors conclude that 3D models can be an invaluable aid during surgery for complex craniovertebral junction anomalies. The information available from a real life-size model supersedes the information available from 3D CT reconstructions and can also be superior to virtual simulation. The models are both cost effective and easy to build and the authors suggest that they may form the basis of investigations in the near future for craniovertebral junction surgery. PMID- 27367940 TI - Low-energy extracorporeal shock wave therapy for promotion of vascular endothelial growth factor expression and angiogenesis and improvement of locomotor and sensory functions after spinal cord injury. AB - OBJECTIVE Extracorporeal shock wave therapy (ESWT) is widely used to treat various human diseases. Low-energy ESWT increases expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. The VEGF stimulates not only endothelial cells to promote angiogenesis but also neural cells to induce neuroprotective effects. A previous study by these authors demonstrated that low-energy ESWT promoted expression of VEGF in damaged neural tissue and improved locomotor function after spinal cord injury (SCI). However, the neuroprotective mechanisms in the injured spinal cord produced by low-energy ESWT are still unknown. In the present study, the authors investigated the cell specificity of VEGF expression in injured spinal cords and angiogenesis induced by low-energy ESWT. They also examined the neuroprotective effects of low-energy ESWT on cell death, axonal damage, and white matter sparing as well as the therapeutic effect for improvement of sensory function following SCI. METHODS Adult female Sprague-Dawley rats were divided into the SCI group (SCI only) and SCI-SW group (low-energy ESWT applied after SCI). Thoracic SCI was produced using a New York University Impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks after SCI. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan open-field locomotor score for 42 days after SCI. Mechanical and thermal allodynia in the hindpaw were evaluated for 42 days. Double staining for VEGF and various cell-type markers (NeuN, GFAP, and Olig2) was performed at Day 7; TUNEL staining was also performed at Day 7. Immunohistochemical staining for CD31, alpha-SMA, and 5-HT was performed on spinal cord sections taken 42 days after SCI. Luxol fast blue staining was performed at Day 42. RESULTS Low-energy ESWT significantly improved not only locomotion but also mechanical and thermal allodynia following SCI. In the double staining, expression of VEGF was observed in NeuN-, GFAP-, and Olig2-labeled cells. Low-energy ESWT significantly promoted CD31 and alpha-SMA expressions in the injured spinal cords. In addition, low-energy ESWT significantly reduced the TUNEL-positive cells in the injured spinal cords. Furthermore, the immunodensity of 5-HT-positive axons was significantly higher in the animals treated by low energy ESWT. The areas of spared white matter were obviously larger in the SCI-SW group than in the SCI group, as indicated by Luxol fast blue staining. CONCLUSIONS The results of this study suggested that low-energy ESWT promotes VEGF expression in various neural cells and enhances angiogenesis in damaged neural tissue after SCI. Furthermore, the neuroprotective effect of VEGF induced by low-energy ESWT can suppress cell death and axonal damage and consequently improve locomotor and sensory functions after SCI. Thus, low-energy ESWT can be a novel therapeutic strategy for treatment of SCI. PMID- 27367941 TI - Radiographic, biomechanical, and histological evaluation of rhBMP-2 in a 3-level intertransverse process spine fusion: an ovine study. AB - OBJECTIVE The objective of this study was to evaluate bone grafts consisting of rhBMP-2 on an absorbable collagen sponge with a ceramic composite bulking agent, rhBMP-2, directly on a ceramic-collagen sponge carrier or iliac crest bone graft (ICBG) in combination with local bone graft to effect fusion in a multisegmental instrumented ovine lumbar intertransverse process fusion model. METHODS Thirty six sheep had a single treatment at 3 spinal levels in both the right and left intertransverse process spaces. Group 1 sheep were treated with 7.5 cm3 of autograft consisting of ICBG plus local bone for each intertransverse process space. For Groups 2-4, 4 cm3 of local bone was placed within the intertransverse process space followed by 4.5-5 cm3 of the rhBMP-2 graft material. Group 2 animals received 1.5 mg/cm3 rhBMP-2 on an absorbable collagen sponge with a commercial bone void filler consisting of Type I lyophilized collagen with a biphasic hydroxyapatite/beta-tricalcium phosphate ceramic with local bone. Group 3 animals received 0.75 mg/m cm3 of rhBMP-2 on a collagen ceramic sponge carrier with local bone. Group 4 animals received 1.35 mg/cm3 of rhBMP-2 on the same collagen ceramic sponge carrier with local bone. Sheep were euthanized 6 months postoperatively. Manual palpation, biomechanical testing, CT, radiography, and undecalcified histology were performed to assess the presence of fusion associated with the treatments. RESULTS All animals in Groups 2-4 that received grafts containing rhBMP-2 achieved radiographic and CT fusion at all 3 levels. In Group 1 (bone autograft alone), only 19% of the levels demonstrated radiographic fusion, 14% resulted in possible radiographic fusion, and 67% of the levels demonstrated radiographic nonfusion. Biomechanical testing showed that Groups 2-4 demonstrated similar stiffness of the L2-5 segment in all 6 loading directions, with each of the 3 groups having significantly greater stiffness than the autograft-only group. In Group 1, only 2 of 18 levels were rated as achieving bilateral histological fusion, with an additional 3 levels showing a unilateral fusion. The majority of the treated levels (13/18) in Group 1 were scored as histological nonfusions. There were no histological nonfusions in Groups 2 through 4. All 18 levels in Group 2 were rated as bilateral histological fusions. A majority (34/36) of the levels in Group 3 were rated as bilateral histological fusions, with 2 levels showing a unilateral fusion. A majority (35/36) of the levels in Group 4 were rated as bilateral histological fusions, with 1 level showing a unilateral fusion. CONCLUSIONS In the ovine multilevel instrumented intertransverse process fusion model, rhBMP-2 was able to consistently achieve CT, radiographic, biomechanical, and histological fusion. Compared with ICBG, the gold standard for bone grafting, rhBMP-2 was statistically superior at achieving radiographic and histological fusion. PMID- 27367942 TI - Endoscopic treatments for rectal neuroendocrine tumors smaller than 16 mm: a meta analysis. AB - OBJECTIVE: Endoscopic mucosal resection (EMR), including conventional EMR (c-EMR) and modified EMR (m-EMR), was applied to remove small rectal neuroendocrine tumors (NETs). We aim to evaluate treatment outcomes of endoscopic submucosal dissection (ESD), m-EMR and c-EMR for rectal NETs <16 mm. METHODS: The PubMed, Cochrane Library and Elsevier Science Direct were searched to identify eligible articles. After quality assessment and data extraction, meta-analysis was performed. The main outcomes were complete resection rate, overall complication rate, procedure time and local recurrence rate. RESULTS: Compared with c-EMR, ESD could achieve higher complete resection rate (OR = 4.38, 95%CI: 2.43-7.91, p < 0.00001) without increasing overall complication rates (OR = 2.21, 95%CI: 0.56 8.70, p = 0.25). However, ESD was more time-consuming than c-EMR (MD = 6.72, 95%CI: 5.84-7.60, p < 0.00001). Compared with m-EMR, ESD did not differ from m EMR in complete resection and overall complication rates (OR = 0.80, 95%CI: 0.51 1.27, p = 0.34; OR = 1.91, 95%CI: 0.75-4.86, p = 0.18, respectively). However, ESD was more time-consuming than m-EMR (MD = 12.21, 95%CI: 7.78-16.64, p < 0.00001). Compared with c-EMR, m-EMR could achieve higher complete resection rate (OR = 4.23, 95%CI: 2.39-7.50, p < 0.00001) without increasing overall complication rate (OR = 1.07, 95%CI: 0.35-3.32, p = 0.90). Moreover, m-EMR was not time-consuming than c-EMR (MD = 2.01, 95%CI: -0.37-4.40, p= 0.10). The local recurrence rate was 0.84% (9/1067) during follow-up. CONCLUSIONS: Both ESD and m EMR have great advantages over c-EMR in complete resection rate without increasing safety concern while m-EMR shares similar outcomes with ESD for rectal NETs <16 mm. The results should be confirmed by well-designed, multicenter, randomized controlled trials with large samples and long-term follow-ups from more countries. PMID- 27367943 TI - Long-term mechanical behaviour of skeletal muscle tissue in semi-confined compression experiments. AB - In this study, porcine skeletal muscle tissue was tested until 112 hours post mortem using a semi-confined compression device that induces fascicles to enter one of the states of compression (mode I), tension (mode II), or constant length (mode III). Based on the authors' previous studies (Bol et al., 2014, 2015a), the anisotropic mechanical behaviour of the tissue was analysed, with a special focus on the testing time post mortem. The results suggest that the tissue exhibits significant anisotropic behaviour during the first hours of post mortem but that this anisotropy becomes insignificant at later time points. Interestingly, the compressibility of the tissue is more or less unaffected by the testing time. These results are discussed especially with respect to tissue microstructure. PMID- 27367944 TI - Uniaxial and biaxial tensile stress-stretch response of human linea alba. AB - There are few studies on the stress-stretch behaviour of human linea alba, yet understanding the mechanics of this tissue is important for developing better methods of abdominal wound closure. Published data focuses mainly on porcine linea alba and for human tissue there are conflicting results and no bi-axial data available. This variability is likely due to challenges with the physical dimensions of the tissue and differences in experimental methodology. This study focussed on the tensile mechanical characterisation of the human linea alba using uniaxial and equi-load biaxial testing performed using image-based strain measurement methods. Thirteen freshly frozen human cadaveric abdominal walls were obtained and used to prepare 7 samples in both the transverse and longitudinal directions for uniaxial testing, and 13 square samples for bi-axial testing. The results showed significant anisotropy and for the equi-load biaxial tests the deformation was heavily biased in the longitudinal direction. In comparison with similar tests on porcine tissue from a previous study, it was found that the response of porcine linea alba to uniaxial loading is similar to that of human linea alba, with no statistically significant differences observed. Under biaxial loading human and porcine linea showed no statistical significance in the difference between their means in the transverse direction. However, a significant difference was observed in the longitudinal direction, and further study of the respective tissue structures is needed to better understand this result. These results provide the first data on the biaxial tensile properties of human linea alba and can aid in an improved assessment of wound closure mechanics. PMID- 27367945 TI - Marian University and the Research Enterprise at Its College of Osteopathic Medicine. PMID- 27367948 TI - Association Between Method of Delivery and Exclusive Breastfeeding at Hospital Discharge. AB - CONTEXT: Studies have shown that exclusive breastfeeding at hospital discharge is associated with longer duration of breastfeeding. Method of delivery (MOD) is a barrier that may hinder breastfeeding practices. However, research examining the association between MOD and exclusive breastfeeding at hospital discharge is lacking. OBJECTIVE: To examine the association between MOD and exclusive breastfeeding at hospital discharge. METHODS: We used a cross-sectional study design to conduct a secondary data analysis of 1494 women who participated in the Infant Feeding Practices Study II between 2005 and 2007. Multiple logistic regression was conducted to estimate the OR and 95% CI for the association between MOD and exclusive breastfeeding at hospital discharge, after adjusting for potential confounding variables. RESULTS: The crude prevalence rates of vaginal delivery and cesarean delivery were 74.8% and 25.2%, respectively. The prevalence of exclusive breastfeeding at hospital discharge was 70.6% among respondents who gave birth by cesarean delivery compared with 79.9% of women who gave birth vaginally (P=.001). After adjusting for sociodemographic, behavioral, and anthropometric factors, the odds of exclusive breastfeeding at hospital discharge were lower among women who gave birth by cesarean delivery compared with women who gave birth vaginally (OR, 0.41; 95% CI, 0.24-0.71). CONCLUSION: Women who give birth by cesarean delivery may require additional attention, assistance, and encouragement during their hospital stay to improve rates of exclusive breastfeeding at discharge. Health care professionals should address the issue of MOD when promoting exclusive breastfeeding to maximize the potential for longer-term breastfeeding success. PMID- 27367949 TI - Targeted Pressure on Abductor Hallucis and Flexor Hallucis Brevis Muscles to Manage Moderate to Severe Primary Restless Legs Syndrome. AB - CONTEXT: Restless legs syndrome (RLS) treatments have included medications with many adverse effects and limited utility. A noninvasive device would potentially have extensive use where RLS medications may not be appropriate, such as in pregnant or breastfeeding women, people with mild RLS, people who operate machinery or drive occupationally, people with severely impaired renal function, or people who are taking medications contraindicated with RLS medications. OBJECTIVE: To assess the efficacy and safety of a device that produces targeted pressure on the abductor hallucis and the flexor hallucis brevis muscles to reduce the symptoms of moderate to severe RLS, and to compare the current findings with findings from studies of ropinirole use in patients with primary RLS. METHODS: This 8-week single-arm, open-label, clinical trial with a repeated measures design was conducted between April 2009 and August 2012 in 2 offices in Erie, Pennsylvania. Adults with moderate to severe primary RLS were recruited for the study. Mean (SD) follow-up was 15.6 (6) months. Patients wore RLS devices (1 on each foot) for set periods intermittently throughout the course of the study. The primary end point was mean change in the International Restless Legs Syndrome Study Group (IRLSSG) Rating Scale from baseline to day 56, and the secondary measure was the Clinical Global Impression scale. A meta-analysis was used to compare the RLS device findings with the findings of 3 historic studies of ropinirole vs placebo. The demographics, disease severity, inclusion and exclusion criteria, and assessment tools were similar among the 4 studies. RESULTS: Thirty patients (22 women, 8 men; mean age, 51.5 years [range, 30-75 years]) participated in the study. Change in mean (SD) IRLSSG score was significantly greater for the RLS device (17.22 [6.16]; P<.001) compared with the ropinirole vs placebo findings (12 [0.86] vs 8.9 [0.86], respectively; P<.05). Sleep loss significantly decreased from 119.5 (61.6) minutes to 22.1 (31.1) minutes per night (P<.001). Global Improvement Scale scores indicated significantly greater improvement with the RLS device compared with ropinirole (27 of 30 [90%] vs 293 of 464 [63%], respectively; P<.05). Mild, transient adverse effects of the device (eg, pain, paresthesia) were reported, but these effects were relieved by loosening the straps. The RLS device demonstrated none of the adverse effects associated with current dopamine agonist therapy, such as augmentation, tolerance, rebound, somnolence, and nausea. CONCLUSION: Producing targeted pressure on the abductor hallucis and flexor hallucis brevis muscles with an external RLS device reduced the symptoms of moderate to severe primary RLS without the adverse effects of medication therapy. (ClinicalTrials.gov number NCT02386423.) J Am Osteopath Assoc. PMID- 27367950 TI - Clinical Relevance and Mechanisms of Antagonism Between the BMP and Activin/TGF beta Signaling Pathways. AB - The transforming growth factor beta (TGF-beta) superfamily is a large group of signaling molecules that participate in embryogenesis, organogenesis, and tissue homeostasis. These molecules are present in all animal genomes. Dysfunction in the regulation or activity of this superfamily's components underlies numerous human diseases and developmental defects. There are 2 distinct arms downstream of the TGF-beta superfamily ligands-the bone morphogenetic protein (BMP) and activin/TGF-beta signaling pathways-and these 2 responses can oppose one another's effects, most notably in disease states. However, studies have commonly focused on a single arm of the TGF-beta superfamily, and the antagonism between these pathways is unknown in most physiologic and pathologic contexts. In this review, the authors summarize the clinically relevant scenarios in which the BMP and activin/TGF-beta pathways reportedly oppose one another and identify several molecular mechanisms proposed to mediate this interaction. Particular attention is paid to experimental findings that may be informative to human pathology to highlight potential therapeutic approaches for future investigation. PMID- 27367951 TI - Quantitative Description of Medical Student Interest in Neurology and Psychiatry. AB - CONTEXT: Given the well-documented shortage of physicians in primary care and several other specialties, quantitative understanding of residency application and matching data among osteopathic and allopathic medical students has implications for predicting trends in the physician workforce. OBJECTIVES: To estimate medical student interest in neurology and psychiatry based on numbers of applicants and matches to neurology and psychiatry osteopathic and allopathic residency programs. Also, to gauge students' previous academic experience with brain and cognitive sciences. METHODS: The number of available postgraduate year 1 positions, applicants, and matches from graduating years 2011 through 2015 were collected from the National Matching Services Inc and the American Association of Colleges of Osteopathic Medicine for osteopathic programs and the National Resident Matching Program and the Association of American Medical Colleges for allopathic programs. To determine and compare osteopathic and allopathic medical students' interest in neurology and psychiatry, the number of positions, applicants, and matches were analyzed considering the number of total osteopathic and allopathic graduates in the given year using 2-tailed chi2 analyses with Yates correction. In addition, osteopathic and allopathic medical schools' websites were reviewed to determine whether neurology and psychiatry rotations were required. Osteopathic medical students' reported undergraduate majors were also gathered. RESULTS: Compared with allopathic medical students, osteopathic medical students had significantly greater interest (as measured by applicants) in neurology (chi21=11.85, P<.001) and psychiatry (chi21=39.07, P<.001), and an equal proportion of osteopathic and allopathic medical students matched in neurology and psychiatry residency programs. Approximately 6% of osteopathic vs nearly 85% of allopathic medical schools had required neurology rotations. Nearly 10% of osteopathic applicants and matriculants had undergraduate coursework in brain and cognitive sciences. CONCLUSION: Osteopathic medical students demonstrated greater interest than allopathic medical students in neurology and psychiatry based on the proportion of residency program applicants but similar interests as measured by matches. Required rotations did not appear to influence students' interests. PMID- 27367952 TI - Assessment of Research Interests of First-Year Osteopathic Medical Students. AB - CONTEXT: According to a 2014 survey, 59% of students entering allopathic medical school reported previous research experience. However, limited data exist on the amount of research experience that students have before entering osteopathic medical school. A strong understanding of the research skills and level of interest of first-year osteopathic medical students is essential for developing research programs at osteopathic medical schools. Limited data exist on the amount of research experience that students have before starting osteopathic medical school. A strong understanding of the research skills and level of interest of first-year medical students is essential for developing research programs at osteopathic medical schools. OBJECTIVE: To determine the amount of previous research experience of first-year osteopathic medical students, their level of interest in participating in research during medical school, the factors influencing their interest in research, and their research fields of interest. METHODS: First-year osteopathic medical students (class of 2019) at the Western University of Health Sciences, College of Osteopathic Medicine of the Pacific in Pomona, California (WesternU/COMP), and Pacific-Northwest in Lebanon, Oregon (WesternU/COMP-Northwest), campuses were surveyed about their previous research experiences and whether they were interested in participating in research during medical school. Surveys were administered through an anonymous online portal. Responses were evaluated for evidence of interest in conducting research. RESULTS: Of the 346 osteopathic medical students invited to participate in the study, the response rate was 77% (N=266). A total of 167 from WesternU/COMP and 99 from the WesternU/COMP-Northwest responded. More than 215 students (81%) reported they had participated in research before entering medical school. In addition, 200 students (75%) either expressed a strong interest in participating in research during medical school or were currently conducting research. Among research areas, clinical research was the overwhelming favorite, with 218 students (82%) expressing interest. CONCLUSION: First-year osteopathic students may have comparable amounts of research experience as allopathic medical students. Although these findings are limited to 2 campuses of 1 osteopathic medical school, they suggest that first-year osteopathic medical students are highly motivated to participate in research while in medical school. PMID- 27367953 TI - Osteopathic Approach to the Diagnosis of Appendiceal Mucinous Cystadenocarcinoma Mimicking Primary Ovarian Malignant Neoplasm. AB - The fifth leading cause of cancer-related deaths among women in the United States is ovarian cancer. An estimated 21,980 new cases and 14,270 estimated deaths occurred nationwide in 2014. More than two-thirds of cases of ovarian cancer are diagnosed at stage III or IV when the peritoneal cavity or other organs are affected. Primary appendiceal malignant neoplasms may mimic advanced-stage ovarian cancer and can be misdiagnosed because of its presentation as a palpable adnexal mass. The authors describe a 42-year-old woman who was admitted to the department of obstetrics and gynecology to receive treatment for presumed advanced-stage ovarian cancer. She subsequently received a diagnosis of primary pseudomyxoma peritonei metastatic to the ovaries, mimicking a primary ovarian cancer by osteopathic structural examination findings, serum tumor markers, surgical exploration, and histopathologic confirmation. PMID- 27367954 TI - Mindfulness-Based Stress Reduction Improves Outcomes in Adults With Chronic Low Back Pain. PMID- 27367955 TI - Craniosacral Therapy Shown Beneficial in Management of Chronic Neck Pain. PMID- 27367956 TI - Educational Interventions May Help Prevent Low Back Pain but Are Not Effective in the Prevention and Treatment of Nonspecific Neck Pain. PMID- 27367957 TI - HVLA or Stretch May Not Be Necessary for Nonspecific Back or Neck Pain Relief. PMID- 27367958 TI - Osteopathic Manipulative Therapy Is Feasible and Safe After Abdominal Surgery. PMID- 27367959 TI - Manual Therapy Technique Shown Beneficial for Osteoarthritis of the Hip. PMID- 27367960 TI - Nodular Torus Palatinus. PMID- 27367961 TI - Management of Cesarean Deliveries and Cesarean Scars With Osteopathic Manipulative Treatment: A Brief Report. AB - Cesarean scars pose a unique set of risks for women who have had previous cesarean deliveries. Between 1996 and 2007, the rate of trial of labor after previous cesarean delivery increased, along with reported rates of uterine rupture and other complications. Consequently, trial of labor after previous cesarean delivery and resultant vaginal birth after cesarean delivery have decreased and cesarean delivery has increased. With nearly one-third of women having cesarean delivery, the rate of rare complications such as cesarean scar ectopic pregnancy has also increased. An integration of osteopathic manipulative treatment techniques into the management of cesarean deliveries and cesarean scars has yet to be defined. The author presents 4 cases of cesarean delivery in which osteopathic manipulative treatment was integrated with successful outcomes. PMID- 27367962 TI - The Importance of Titrating Antibodies for Immunocytochemical Methods. AB - When using immunocytochemistry, investigators may not know how to optimize staining or how to troubleshoot the method when staining fails. Lacking are guides for comparing techniques and applying information derived from one staining method to another. Newer methods amplify signal detection, but will not necessarily work at the same primary antibody concentrations used for less sensitive reactions. Recommendations of optimal titers are often not accurate and are not usually accompanied by information on the method used to test those antibodies or the specifics of the assay. When the staining does not work, the investigators do not know how to determine if the antiserum is bad, the tissue is bad, or the method is inappropriate for their staining. This unit describes detailed procedures for determining optimal staining and applying that information to three common immunofluorescence methods. Lastly, a formula is provided for converting among the different methods. (c) 2016 by John Wiley & Sons, Inc. PMID- 27367963 TI - Extraction, Identification, and Quantification of Histones from Small Quantities of Specific Brain Tissue. AB - Histone posttranslational modifications (PTMs), by their action on the chromatin state, play a central role in the regulation of gene expression. The discovery that some PTMs in the brain are dynamically regulated by experience and environmental factors makes them an important subject for the study of plasticity changes in learning and memory, addiction, and psychiatric disorders. Current histone isolation protocols, however, require large amounts of tissue, which limits their application for analyzing small tissue samples from a specific brain region. We describe here a step-by-step protocol for histone extraction and isolation from 1 mm(3) of tissue from brain punches, which allows reproducible and reliable results for histone PTM identification and quantification without losing anatomical precision. (c) 2016 by John Wiley & Sons, Inc. PMID- 27367964 TI - Daun02 Inactivation of Behaviorally Activated Fos-Expressing Neuronal Ensembles. AB - Learned associations about salient experiences (e.g., drug exposure, stress) and their associated environmental stimuli are mediated by a minority of sparsely distributed, behaviorally activated neurons coined 'neuronal ensembles.' For many years, it was not known whether these neuronal ensembles played causal roles in mediating learned behaviors. However, in the last several years the 'Daun02 inactivation technique' in Fos-lacZ transgenic rats has proved very useful in establishing causal links between neuronal ensembles that express the activity regulated protein Fos and learned behaviors. Fos-expressing neurons in these rats also express the bacterial protein beta-galactosidase (beta-gal) in strongly activated neurons. When the prodrug Daun02 is injected into the brains of these rats 90 min after a behavior (e.g., drug-seeking) or cue exposure, then Daun02 is converted into daunorubicin by beta-gal, which selectively inactivates Fos- and beta-gal-expressing neurons that were activated 90 min before the Daun02 injection. This unit presents protocols for breeding the Fos-lacZ rats and conducting appropriate Daun02 inactivation experiments. (c) 2016 by John Wiley & Sons, Inc. PMID- 27367965 TI - Feasibility of binary composition in development of nanoethosomal glycolic vesicles of triamcinolone acetonide using Box-behnken design: in vitro and ex vivo characterization. AB - Triamcinolone acetonide (TA) employed for the treatment of atopic dermatitis exhibits limited penetration into the epidermis. This investigation aimed to explore the role of binary solvents in topical drug delivery of TA by developing nanoethosomal glycolic lipid vesicles by infusion method. Screening of vesicles (TA1-TA17) formulated by Box Behnken design identified the optimized formulation (TA10) that was developed as carbomer gels. The gels were then evaluated for pharmaceutical properties and compared with control and reference ethosomal gel (RG). Higher in vitro permeation was found in gels containing TA10, prepared with or without using penetration enhancer (EGP 83.76 +/- 0.72% and EG 82.42 +/- 0.89%, respectively). CLSM studies depicted deeper uniform penetration of fluorescent tracer into the epidermis via EG as compared with RG and control gel. Enhanced penetration was due to combinational solvent effect exerted by ethanol and propylene glycol. Histological analysis confirmed the non-irritant potential of the gel. Thus, it can be concluded that nanoethosomal glycolic vesicles proved to be an effective non irritant carrier for improvised penetration of triamcinolone acetonide for potential topical therapeutics. PMID- 27367966 TI - An event-specific method for the detection and quantification of ML01, a genetically modified Saccharomyces cerevisiae wine strain, using quantitative PCR. AB - The availability of genetically modified (GM) yeasts for winemaking and, in particular, transgenic strains based on the integration of genetic constructs deriving from other organisms into the genome of Saccharomyces cerevisiae, has been a reality for several years. Despite this, their use is only authorized in a few countries and limited to two strains: ML01, able to convert malic acid into lactic acid during alcoholic fermentation, and ECMo01 suitable for reducing the risk of carbamate production. In this work we propose a quali-quantitative culture-independent method for the detection of GM yeast ML01 in commercial preparations of ADY (Active Dry Yeast) consisting of efficient extraction of DNA and qPCR (quantitative PCR) analysis based on event-specific assay targeting MLC (malolactic cassette), and a taxon-specific S. cerevisiae assay detecting the MRP2 gene. The ADY DNA extraction methodology has been shown to provide good purity DNA suitable for subsequent qPCR. The MLC and MRP2 qPCR assay showed characteristics of specificity, dynamic range, limit of quantification (LOQ) limit of detection (LOD), precision and trueness, which were fully compliant with international reference guidelines. The method has been shown to reliably detect 0.005% (mass/mass) of GM ML01 S. cerevisiae in commercial preparations of ADY. PMID- 27367967 TI - Controlled mixed fermentation at winery scale using Zygotorulaspora florentina and Saccharomyces cerevisiae. AB - Over the last few years the use of multi-starter inocula has become an attractive biotechnological practice in the search for wine with high flavour complexity or distinctive characters. This has been possible through exploiting the particular oenological features of some non-Saccharomyces yeast strains, and the effects that derive from their specific interactions with Saccharomyces. In the present study, we evaluated the selected strain Zygotorulaspora florentina (formerly Zygosaccharomyces florentinus) in mixed culture fermentations with Saccharomyces cerevisiae, from the laboratory scale to the winery scale. The scale-up fermentation and substrate composition (i.e., white or red musts) influenced the analytical composition of the mixed fermentation. At the laboratory scale, mixed fermentation with Z. florentina exhibited an enhancement of polysaccharides and 2 phenylethanol content and a reduction of volatile acidity. At the winery scale, different fermentation characteristics of Z. florentina were observed. Using Sangiovese red grape juice, sequential fermentation trials showed a significantly higher concentration of glycerol and esters while the sensorial analysis of the resulting wines showed higher floral notes and lower perception of astringency. To our knowledge, this is the first time that this yeasts association has been evaluated at the winery scale indicating the potential use of this mixed culture in red grape varieties. PMID- 27367968 TI - Quantification of Toxins in Soapberry (Sapindaceae) Arils: Hypoglycin A and Methylenecyclopropylglycine. AB - Methylenecyclopropylglycine (MCPG) and hypoglycin A (HGA) are naturally occurring amino acids found in some soapberry fruits. Fatalities have been reported worldwide as a result of HGA ingestion, and exposure to MCPG has been implicated recently in the Asian outbreaks of hypoglycemic encephalopathy. In response to an outbreak linked to soapberry ingestion, the authors developed the first method to simultaneously quantify MCPG and HGA in soapberry fruits from 1 to 10 000 ppm of both toxins in dried fruit aril. Further, this is the first report of HGA in litchi, longan, and mamoncillo arils. This method is presented to specifically address the laboratory needs of public-health investigators in the hypoglycemic encephalitis outbreaks linked to soapberry fruit ingestion. PMID- 27367969 TI - Association Between Socioeconomic Status and Mortality, Cardiovascular Disease, and Cancer in Patients With Type 2 Diabetes. AB - IMPORTANCE: The association between socioeconomic status and survival based on all-cause, cardiovascular (CV), diabetes-related, and cancer mortality in type 2 diabetes has not been examined in a setting of persons with equitable access to health care with adjustment for important confounders. OBJECTIVE: To determine whether income, educational level, marital status, and country of birth are independently associated with all-cause, CV, diabetes-related, and cancer mortality in persons with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: A study including all 217 364 individuals younger than 70 years with type 2 diabetes in the Sweden National Diabetes Register (January 1, 2003, to December 31, 2010) who were monitored through December 31, 2012, was conducted. A Cox proportional hazards regression model with up to 17 covariates was used for analysis. MAIN OUTCOMES AND MEASURES: All-cause, CV, diabetes-related, and cancer mortality. RESULTS: Of the 217 364 persons included in the study, mean (SD) age was 58.3 (9.3) years and 130 839 of the population (60.2%) was male. There were a total of 19 105 all-cause deaths with 11 423 (59.8%), 6984 (36.6%), and 6438 (33.7%) CV, diabetes-related, or cancer deaths, respectively. Compared with being single, hazard ratios (HRs) for married individuals, determined using fully adjusted models, for all-cause, CV, and diabetes-related mortality were 0.73 (95% CI, 0.70-0.77), 0.67 (95% CI, 0.63-0.71), and 0.62 (95% CI, 0.57-0.67), respectively. Marital status was not associated with overall cancer mortality, but married men had a 33% lower risk of prostate cancer mortality compared with single men, with an HR of 0.67 (95% CI, 0.50-0.90). Comparison of HRs for the lowest vs highest income quintiles for all-cause, CV, diabetes-related, and cancer mortality were 1.71 (95% CI, 1.60-1.83), 1.87 (95% CI, 1.72-2.05), 1.80 (95% CI, 1.61-2.01), and 1.28 (95% CI, 1.14-1.44), respectively. Compared with native Swedes, HRs for all-cause, CV, diabetes-related, and cancer mortality for non-Western immigrants were 0.55 (95% CI, 0.48-0.63), 0.46 (95% CI, 0.38-0.56), 0.38 (95% CI, 0.29-0.49), and 0.72 (95% CI, 0.58-0.88), respectively, and these HRs were virtually unaffected by covariate adjustment. Hazard ratios for those with a college/university degree compared with 9 years or less of education were 0.85 (95% CI, 0.80-0.90), 0.84 (95% CI, 0.78-0.91), and 0.84 (95% CI, 0.76-0.93) for all-cause, CV, and cancer mortality, respectively. CONCLUSIONS AND RELEVANCE: Independent of risk factors, access to health care, and use of health care, socioeconomic status is a powerful predictor of all-cause and CV mortality but was not as strong as a predictor of death from cancer. PMID- 27367970 TI - Reduced growth during early infancy in very low birth weight children with autism spectrum disorder. PMID- 27367971 TI - Parallax error in long-axial field-of-view PET scanners-a simulation study. AB - There is a growing interest in the design and construction of a PET scanner with a very long axial extent. One critical design challenge is the impact of the long axial extent on the scanner spatial resolution properties. In this work, we characterize the effect of parallax error in PET system designs having an axial field-of-view (FOV) of 198 cm (total-body PET scanner) using fully-3D Monte Carlo simulations. Two different scintillation materials were studied: LSO and LaBr3. The crystal size in both cases was 4 * 4 * 20 mm3. Several different depth-of interaction (DOI) encoding techniques were investigated to characterize the improvement in spatial resolution when using a DOI capable detector. To measure spatial resolution we simulated point sources in a warm background in the center of the imaging FOV, where the effects of axial parallax are largest, and at several positions radially offset from the center. Using a line-of-response based ordered-subset expectation maximization reconstruction algorithm we found that the axial resolution in an LSO scanner degrades from 4.8 mm to 5.7 mm (full width at half max) at the center of the imaging FOV when extending the axial acceptance angle (alpha) from +/-12 degrees (corresponding to an axial FOV of 18 cm) to the maximum of +/-67 degrees -a similar result was obtained with LaBr3, in which the axial resolution degraded from 5.3 mm to 6.1 mm. For comparison we also measured the degradation due to radial parallax error in the transverse imaging FOV; the transverse resolution, averaging radial and tangential directions, of an LSO scanner was degraded from 4.9 mm to 7.7 mm, for a measurement at the center of the scanner compared to a measurement with a radial offset of 23 cm. Simulations of a DOI detector design improved the spatial resolution in all dimensions. The axial resolution in the LSO-based scanner, with alpha = +/- 67 degrees , was improved from 5.7 mm to 5.0 mm by incorporating a two-layer DOI detector. These results characterize the maximum axial blurring for a fully open 2 m long PET scanner and demonstrate that large sensitivity gains are possible with a modest reduction in resolution when using current clinical detector technology with no DOI capability. PMID- 27367972 TI - Minimal Hearing Loss: From a Failure-Based Approach to Evidence-Based Practice. AB - PURPOSE: A representative sample of the literature on minimal hearing loss (MHL) was reviewed to provide evidence of challenges faced by children with MHL and to establish the need for evidence-based options for early intervention. METHOD: Research articles published from 1950 to 2013 were searched in the Medline database using the keywords minimal hearing loss, unilateral hearing loss, and mild hearing loss. References cited in retrieved articles were also reviewed. RESULTS: In total, 69 articles contained relevant information about pediatric outcomes and/or intervention for unilateral hearing loss, 50 for mild hearing loss, and 6 for high-frequency hearing loss. Six challenges associated with MHL emerged, and 6 interventions were indicated. Evidence indicates that although some individuals may appear to have no observable speech-language or academic difficulties, others experience considerable difficulties. It also indicates that even though children with MHL may appear to catch up in some areas, difficulties in select domains continue into adulthood. CONCLUSIONS: Evidence indicates significant risks associated with untreated MHL. Evidence also demonstrates the need for early intervention and identifies several appropriate intervention strategies; however, no single protocol is appropriate for all children. Therefore, families should be educated about the impact of MHL and about available interventions so that informed decisions can be made. PMID- 27367974 TI - Syrian Civil-War-Related Intraocular Foreign Body Injuries: A Four-Year Retrospective Analysis. AB - PURPOSE: To analyze the data of patients who underwent vitreoretinal surgery due to intraocular foreign body (IOFB) injuries that occurred in the Syrian civil war. METHODS: Seventy-eight eyes of 78 patients who underwent vitreoretinal surgery due to IOFB injuries that occurred during the Syrian civil war were analyzed. RESULTS: Forty-four eyes (56.4%) had traumatic cataract, 44 (56.4%) had retinal tears, 42 (53.8%) had vitreous hemorrhage, 18 (23%) had retinal detachment, 12 (15.3%) had endophthalmitis, and eight eyes had hyphema (10.2%). IOFBs consisted of metal in 62 eyes (79.4%), stone in eight eyes (10.2%), organic material in four eyes (5.1%), and glass in four eyes (5.1%). Approximately 86% of the eyes had initial VAs of 4/200 or worse. However, VAs improved in 64 eyes (82%) after the surgeries. CONCLUSIONS: Despite delays in treatment and the severity of injuries, 82% (64/78) of the eyes had an improvement in VA after the surgeries. PMID- 27367973 TI - Comparison of analytical techniques for the identification of bioactive compounds from natural products. AB - Covering: 2000 to 2016Natural product extracts are a rich source of bioactive compounds. As a result, the screening of natural products for the identification of novel biologically active metabolites has been an essential part of several drug discovery programs. It is estimated that more than 70% of all drugs approved from 1981 and 2006, were either derived from or structurally similar to nature based compounds indicating the necessity for the development of a rapid method for the identification of novel compounds from plant extracts. The screening of biological matrices for the identification of novel modulators is nevertheless still challenging. In this review we discuss current techniques in phytochemical analysis and the identification of biologically active components. PMID- 27367975 TI - Temporary Balloon Occlusion of the Abdominal Aorta in Treatment of Complex Acetabular Fracture. AB - BACKGROUND The aim of this study was to explore the efficacy of temporary balloon occlusion of the abdominal aorta assisting open reduction and internal fixation (ORIF) in the treatment of complex acetabular fracture. MATERIAL AND METHODS From August 2000 to October 2011, a total of 48 patients with complex acetabular fracture were enrolled in this study. Average operative time, intraoperative blood loss volume, blood transfusion volume, satisfactory reduction, and postoperative functional recovery rate were recorded and compared between the 2 groups. RESULTS A significant difference was observed between the 2 groups in operative time (P=0.003). For intraoperative blood loss and blood transfusion, ORIF combined with temporary balloon occlusion of abdominal aorta techniques appeared to be superior to normal ORIF (blood loss: P=0.007; and blood transfusion: P=0.019, respectively). However, no differences were observed in postoperative blood loss or transfusion (P>0.05). Patients in group A showed better hip function than those in group B (group A: a good-to-excellent rate of 77.8%; group B: a good-to-excellent rate of 78.3%; P>0.05). With regard to the incidence of postoperative complications, there were no significant differences between the 2 groups (group A: 9/18; group B: 11/23; P=0.890). CONCLUSIONS In the treatment of complex acetabular fracture, temporary balloon occlusion of the abdominal aorta is a reliable technique to assist ORIF surgery to staunch the flow of blood. PMID- 27367976 TI - Immature mediastinal teratoma with unusual histopathology: A case report of multi lineage, somatic-type malignant transformation and a review of the literature. AB - Germ cell tumors (GCTs) represent a well-recognized group of heterogeneous neoplasms with diverse clinical, histopathological, diagnostic, and prognostic characteristics. We present a rare case of a locally aggressive, chemotherapy resistant immature mediastinal teratoma with a peculiar histological finding of a multilineage somatic-type malignant degeneration. A 21-year-old male patient presented with a 3-week history of persistent, blood-tinged productive cough and shortness of breath. A contrast-enhanced computed tomography (CT) scan of the chest showed a heterogeneous mass occupying the right hemithorax and abutting on adjacent structures. CT-guided biopsy was consistent with immature teratoma. Combination chemotherapy with bleomycin, etoposide, and cisplatin was initiated, albeit without success; the mass showed interval progression in size, and surgical resection through clamshell incision was performed. Histological assessment of the resected mass confirmed the diagnosis of immature teratoma and revealed an extensive multilineage malignant differentiation into sarcomatous, carcinomatous, and melanomatous components. The patient underwent an uneventful recovery but presented 2 months later with extensive liver and bone melanomatous metastases. In this report, relevant findings from the literature are also highlighted. Despite being exceptionally rare, such tumors carry poor prognosis. Understanding the clinicopathological characteristics and biological behavior of such tumors may provide an insight into interventions tailored to improve the otherwise dismal disease outlook. PMID- 27367977 TI - Simple risk factors to predict urgent endoscopy in nonvariceal upper gastrointestinal bleeding pre-endoscopically. AB - The goal of this study is to evaluate how to predict high-risk nonvariceal upper gastrointestinal bleeding (NVUGIB) pre-endoscopically. A total of 569 NVUGIB patients between Match 2011 and January 2015 were retrospectively studied. The clinical characteristics and laboratory data were statistically analyzed. The severity of NVUGIB was based on high-risk NVUGIB (Forrest I-IIb), and low-risk NVUGIB (Forrest IIc and III). By logistic regression and receiver-operating characteristic curve, simple risk score systems were derived which predicted patients' risks of potentially needing endoscopic intervention to control bleeding. Risk score systems combined of patients' serum hemoglobin (Hb) <=75 g/L, red hematemesis, red stool, shock, and blood urine nitrogen >=8.5 mmol/L within 24 hours after admission were derived. As for each one of these clinical signs, the relatively high specificity was 97.9% for shock, 96.4% for red stool, 85.5% for red hematemesis, 76.7% for Hb <=75 g/L, and the sensitivity was 50.8% for red hematemesis, 47.5% for Hb <=75 g/L, 14.2% for red stool, and 10.9% for shock. When these 5 clinical signs were presented as a risk score system, the highest area of receiver-operating characteristic curve was 0.746, with sensitivity 0.675 and specificity 0.733, which discriminated well with high-risk NVUGIB. These simple risk factors identified patients with high-risk NVUGIB of needing treatment to manage their bleeding pre-endoscopically. Further validation in the clinic was required. PMID- 27367978 TI - Demographic and clinical characteristics related to cognitive decline in Alzheimer disease in China: A multicenter survey from 2011 to 2014. AB - Alzheimer disease (AD) is the most frequent cause of dementia. AD diagnosis, progression, and treatment have not been analyzed nationwide in China. The primary aim of this study was to analyze demographic and clinical characteristics related to cognitive decline in AD patients treated at outpatient clinics in China.We performed a retrospective study of 1993 AD patients at 10 cognitive centers across 8 cities in China from March 2011 to October 2014. Of these, 891 patients were followed for more than 1 year.The mean age at diagnosis was 72.0 +/ 10.0 years (range 38-96 years), and the mean age at onset of AD was 69.8 +/- 9.5 years. Most patients (65.1%) had moderate to severe symptoms at the time of diagnosis, and mean Mini-Mental State Examination at diagnosis was 15.7 +/- 7.7. AD patients showed significant cognitive decline at 12 months after diagnosis. Having more than 9 years of formal education was an independent risk factor related to rapid cognitive decline [odds ratio (OR) = 1.80; 95% confidence interval (95% CI): 1.11-2.91]. Early-onset AD patients experienced more rapid cognitive decline than late-onset patients (OR = 1.83; 95% CI: 1.09-3.06).Most AD patients in China had moderate to severe symptoms at the time of diagnosis and experienced significant cognitive decline within 1 year. Rapid cognitive decline in AD was related to having a higher educational level and younger age of onset. PMID- 27367979 TI - Susceptibility-weighted MRI of extrapyramidal brain structures in Parkinsonian disorders. AB - Susceptibility-weighted MRI (SWI) is sensitive to T2 effects and mineralization.We investigated differences in the extrapyramidal brain structures on SWI between Parkinson disease (PD) and postural instability gait disorder (PIGD) patients and correlated the SWI values with the degree of gait dysfunction.Forty patients diagnosed with PD and PIGD underwent 3 Tesla magnetic resonance imaging (MRI) brain study. An SWI sequence (TE/TR/FA 20/33/15) was used. Ten regions of interest were placed in the midbrain and basal ganglia by 2 independent raters blinded to subject data and quantitatively evaluated.The inter rater reliability between the raters was excellent (interclass correlation coefficient >0.8). The SWI intensity values in all regions were on average lower in PIGD than in PD patients, with the lowest results found in globus pallidus.Multivariate analysis showed a lower SWI hypointensity in the putamen and globus pallidus in PIGD compared with PD patients, with a similar trend for the other basal ganglia nuclei. Pearson correlation analysis showed a statistically significant positive correlation between SWI putaminal hypointensity and the Tinetti total score (r = 0.39, P = 0.01) in both PD and PIGD.SWI putaminal hypointensity may be a useful imaging marker in prospective evaluation for clinical progression for Parkinsonian disorders. PMID- 27367980 TI - Factors affecting patient outcome in primary cutaneous aspergillosis. AB - Primary cutaneous aspergillosis (PCA) is an uncommon infection of the skin. There is a paucity of organized literature regarding this entity in regard to patient characteristics, associated Aspergillus species, and treatment modalities on outcome (disease recurrence, disease dissemination, and mortality).We reviewed all published reports of PCA from 1967 to 2015. Cases were deemed eligible if they included the following: patient baseline characteristics (age, sex, underlying condition), evidence of proven or probable PCA, primary treatment strategy, and outcome.We identified 130 eligible cases reported from 1967 to 2015. The patients were predominantly male (63.8%) with a mean age of 30.4 +/- 22.1 years. Rates of PCA recurrence, dissemination, and mortality were 10.8%, 18.5%, and 31.5%, respectively. In half of the cases, there was an association with a foreign body. Seven different Aspergillus species were reported to cause PCA. Systemic antifungal therapy without surgery was the most common form of therapy (60% of cases). Disease dissemination was more common in patients with underlying systemic conditions and occurred on average 41.4 days after PCA diagnosis (range of 3-120 days). In a multivariate linear regression model of mortality including only patients with immunosuppressive conditions, dissemination and human immunodeficiency virus/acquired immune deficiency syndrome were statistically significantly associated with increased mortality.Nearly one-third of patients with PCA die with the disease. Dissemination and host status are critical in patient outcome. PMID- 27367981 TI - Successful surgical treatment of scoliosis secondary to Guillain-Barre syndrome: Case report. AB - Guillain-Barre syndrome (GBS) is an acute autoimmune inflammatory demyelinating polyneuropathy that mostly affects the peripheral nervous system. Little is reported about spinal deformity associated with GBS. This study aims to present a case of scoliosis occurring in the setting of GBS.Case report and literature review.The patient was a 14-year-old male with scoliosis. His spinal plain radiographs showed that the Cobb angle of thoracic scoliosis was 114 degrees . History review revealed that he developed profound lower extremity pain, weakness, and numbness after catching a cold 5 years ago. These symptoms progressed to unsteady gait and inability to stand up from squatting position. The diagnosis of GBS was confirmed based on these symptoms. He underwent a posterior correction at Thoracic 5-Lumbar 5 (T5-L12) levels using the (LEGACY, USA) spinal system. The Cobb angle was corrected from 114 degrees to 45 degrees (correction rate 60.5%). His follow-up was symptomatic, well balanced in the coronal planes, with solid fusion 12 months after the operation.Neuromuscular scoliosis could develop secondary to GBS. When evaluating patients with acute inflammatory polyneuropathy, clinical examination of the spine is essential to identify patients with rare neuromuscular scoliosis. PMID- 27367982 TI - Correlation between the different pH-metry scores in gastroesophageal reflux disease in children. AB - The 24-hour esophageal pH-metry is the most widely used method to diagnose the gastroesophageal reflux disease (GERD). The study compares the different scores obtained during the 24-hour esophageal pH-metry. A retrospective study over 5 years including 234 children (1 month and 18 years old) admitted in a pediatric gastroenterology regional center in Northeast Romania, with suspicion of GERD. They underwent 24- hour esophageal pH-metry, and the scores obtained (Boix-Ochoa, DeMeester, Johnson-DeMeester) were compared. Out of the 234 children, 172 (73.50%) had positive Boix-Ochoa score and 62 (26.50%) had normal Boix-Ochoa score (<11.99). Based on the DeMeester score, 149 children (63.68%) were positive and 85 (36.32%) were negative. The correlation of the Demeester score with the Boix-Ochoa score was very high (r = 0.978, P < < 0.01, 95% confidence interval). Considering the Johnson-DeMeester score, 120 cases (51.28%) had GERD and 114 (48.72%) did not. The correlation of the Johnson-DeMeester score with the Boix Ochoa score was still high (r = 0.94, P < < 0.01, 95% 95% confidence interval). As considered until now, the Boix-Ochoa score is the most accurate score to be used in pediatrics for the diagnosis of GERD. The use of the different scores Boix-Ochoa, DeMeester, Johnson-DeMeester-showed a high sensitivity and specificity of the pH-metry measurements applied to the study lot, but the last score has a higher risk of false-negative results. PMID- 27367983 TI - Loss of tubular creatinine secretion as the only sign of tubular proximal cell dysfunction in light chain proximal tubulopathy: A case report. AB - Light chain proximal tubulopathy (LCPT) is a rare disease, characterized by cytoplasmic inclusions of light chain (usually kappa) immunoglobulins. Clinical presentation is usually a Fanconi syndrome. The proximal tubular dysfunction can be incomplete, and exceptional cases of LCPT without any tubular dysfunction have even been described. Here, we report a case of LCPT in which the only sign of proximal tubulopathy is the absence of secretion of creatinine, as assessed by the simultaneous measurement of renal clearance of creatinine and CrEDTA. The loss of tubular creatinine secretion as a sign of tubular proximal cell dysfunction ought to be identified in patients with light chain proximal tubulopathy as it leads to a clinically relevant underestimation of GFR by the creatinine-derived equations. The prevalence and prognostic significance of this particular proximal tubular damage in LCPT remain to be determined. PMID- 27367984 TI - Giant-cell arteritis without cranial manifestations: Working diagnosis of a distinct disease pattern. AB - Diagnosis of giant-cell arteritis (GCA) is challenging in the absence of cardinal cranial symptoms/signs. We aimed to describe the clinical presentation, diagnostic process, and disease course of GCA patients without cranial symptoms, and to compare them to those of patients with typical cranial presentation. In this retrospective multicenter study, we enrolled patients with GCA who satisfied at least 3 of the 5 American College of Rheumatology criteria for GCA, or 2 criteria associated with contributory vascular biopsy other than temporal artery biopsy or with demonstration of large-vessel involvement; underwent iconographic evaluation of large arterial vessels (aortic CT scan or a positron emission tomography with F-fluorodeoxyglucose combined with computed tomography (FDG PET/CT) scan or cardiac echography combined with a large-vessel Doppler) at diagnosis. We divided the cohort into 2 groups, distinguishing between patients without cranial symptoms/signs (i.e., headaches, clinical temporal artery anomaly, jaw claudication, ophthalmologic symptoms) and those with cranial symptoms/signs. In the entire cohort of 143 patients, all of whom underwent vascular biopsy and vascular imaging, we detected 31 (22%) patients with no cranial symptoms/signs. In the latter, diagnosis was biopsy proven in an arterial sample in 23 cases (74% of patients, on a temporal site in 20 cases and on an extratemporal site in 3). One-third of these 31 patients displayed extracranial symptoms/signs whereas the remaining two-thirds presented only with constitutional symptoms and/or inflammatory laboratory test results. Compared to the 112 patients with cardinal cranial clinical symptoms/signs, patients without cranial manifestations displayed lower levels of inflammatory laboratory parameters (C-reactive level: 68 [9-250] mg/L vs 120 [3-120] mg/L; P < 0.01), highest rate of aorta and aortic branch involvement identified (19/31 (61%) vs 42/112 (38%); P = 0.02) and also a lower rate of disease relapse (12/31 (39%) vs 67/112 (60%); P = 0.04). Our results suggest that patients without cranial symptoms/signs are prone to lower inflammatory laboratory parameters, fewer relapses, and more large-vessel involvement than those displaying cardinal cranial manifestations. Further studies are therefore required in order to determine whether these 2 subgroups of patients have a different prognosis, and therefore warrant different therapeutic and monitoring regimens. PMID- 27367985 TI - 18F-fluorodeoxyglucose positron emission tomography and the risk of subsequent aortic complications in giant-cell arteritis: A multicenter cohort of 130 patients. AB - Previous studies reported a 2- to 17-fold higher risk of aortic complications (dilation or dissection) in patients with giant-cell arteritis (GCA). We aimed to determine whether or not GCA patients with large-vessel involvement demonstrated by positron emission tomography with F-fluorodeoxyglucose combined with computed tomography (FDG-PET/CT) have a higher risk of aortic complications. We conducted a retrospective multicenter study between 1995 and 2014. Patients were included if they fulfilled at least 3 American College of Rheumatology criteria for GCA, or 2 criteria associated with extratemporal biopsy-proven giant-cell vasculitis; they underwent at least 1 FDG-PET/CT scan at diagnosis or during follow-up; and the morphology of the aorta was assessed by medical imaging at diagnosis. Patients with an aortic complication at the time of diagnosis were excluded. Of the 130 patients included [85 women (65%), median age 70 (50-86)], GCA was biopsy proven in 77 (59%). FDG-PET/CT was performed at diagnosis in 63 (48%) patients and during the follow-up period in the 67 (52%) remaining patients. FDG-PET/CT was positive in 38/63 (60%) patients at diagnosis and in 31/67 (46%) patients when performed during follow-up (P = NS). One hundred four patients (80%) underwent at least 1 morphological assessment of the aorta during follow-up. Nine (9%) patients developed aortic complications (dilation in all and dissection in 1) at a median time of 33 (6-129) months after diagnosis. All of them displayed large-vessel inflammation on previous FDG-PET/CT. A positive FDG-PET/CT was significantly associated with a higher risk of aortic complications (P = 0.004).In our study, a positive FDG-PET/CT was associated with an increased risk of aortic complications at 5 years. PMID- 27367986 TI - Spontaneous spinal epidural hematoma management with minimally invasive surgery through tubular retractors: A case report and review of the literature. AB - To report a minimally invasive paraspinal approach in the treatment of a case of spontaneous spinal epidural hematoma (SSEH). We additionally aim to review the relevant literature to enhance our knowledge of this disease. SSEH is an uncommon but potentially catastrophic disease. Currently, most appropriate management is emergence decompression laminectomy and hematoma evacuation. An 81-year-old woman was admitted to the neurology department with a chief complaint of bilateral numbness and weakness of the lower limbs and difficulty walking for 4 days with progressive weakness developed over the following 3 days accompanied with pain in the lower limbs and lower back. No history of trauma was reported. Magnetic resonance imaging of the thoracolumbar spine demonstrated an epidural hematoma extending from T-12 to L-5 with thecal sac and cauda equina displacement anterior. The patient was treated in our department with a minimally invasive approach. This operation method had been approved by Chinese Independent Ethics Committee. Three months following the operation, the patient had regained the ability to walk with the aid of a cane and myodynamia tests revealed normal results for the left lower limb and a 4/5 grade for the right limb. Importantly, no complications were exhibited from the surgical operation. The minimally invasive paraspinal approach through tubular retractors is demonstrated here as an effective alternative method for the treatment of SSEH. PMID- 27367987 TI - Butorphanol suppresses fentanyl-induced cough during general anesthesia induction: A randomized, double-blinded, placebo-controlled clinical trial. AB - Fentanyl-induced cough (FIC) is unwanted in the patients requiring stable induction of general anesthesia. This study was designed to evaluate the suppressive effects of butorphanol pretreatment on the incidence and severity of FIC during the induction of general anesthesia. A total of 315 patients of American Society of Anesthesiologists physical status I and II, scheduled for elective surgery under general anesthesia were randomized into 3 equally sized groups (n = 0105). Two minutes before fentanyl bolus, group I received intravenously 5 mL normal saline, groups II and III received butorphanol 0.015 and 0.03 mg/kg (diluted with saline to 5 mL), respectively. Patients were then administrated with fentanyl 2.5 MUg/kg within 5 s. The incidence and severity of FIC was recorded for 2 minutes after fentanyl bolus. During experimental period, the mean arterial pressure, heart rate, and peripheral capillary oxygen saturation (SpO2) were recorded before the administration of butorphanol or normal saline (T0), 2 minutes (T1) after butorphanol injection, and 2 minutes (T2) after fentanyl injection. The incidence of FIC was 31.4% in group I, 11.4% in group II, and 3.8% in group III. Group III had a lowest incidence of FIC among 3 groups (P < 0.001, vs group I; P < 0.05, vs group II). The severe FIC was not observed in groups II and III, but was recoded from 6 patients in group I. At 2 minutes after fentanyl injection (T2), the mean arterial pressure was significantly higher in group I than that in groups II and III (P < 0.01, vs group II; P < 0.05, vs group III), but the values remained within safe limits. In conclusion, pretreatment with butorphanol could effectively and safely suppress FIC during anesthesia induction. PMID- 27367988 TI - Intraoperative portal vein insulin assay combined with occlusion of the pancreas for complex pancreatogenous hypoglycemia: Two cases report. AB - Intraoperative localization and confirmation of complete resection of the hypersecreting tissue are the 2 main challenges in the management of pancreatogenous hypoglycemia. Here, we report our experience with intraoperative portal vein insulin assay combined with occlusion of the pancreas in the management of pancreatogenous hypoglycemia. Clinical courses of 2 patients with biochemical evidence of a pancreatogenous hypoglycemia were studied. The preoperative diagnosis was multiple endocrine neoplasia 1 (MEN-1) and nesidioblastosis, respectively. Rapid intraoperative portal vein insulin assay combined with occlusion of the pancreas was used to localize and confirm complete excision of the hypersecreting tissue. Hypoglycemia was successfully treated in both the patients. In the MEN-1 patient, 2 small tumors in the head of pancreas were not resected, as they were deemed noninsulin secreting by intraoperative portal vein insulin assay, thus avoiding a total pancreatectomy. In the patient with nesidioblastosis, using intraoperative portal vein insulin assay combined with occlusion of the pancreas, an appropriate amount of pancreatic tissue was resected thereby avoiding recurrence and diabetes. This technique may be of particular value in patients with complex conditions such as MEN-1 and nesidioblastosis, to localize and achieve complete resection of hypersecreting pancreatic tissue. PMID- 27367989 TI - Time series analysis of influenza incidence in Chinese provinces from 2004 to 2011. AB - Influenza as a severe infectious disease has caused catastrophes throughout human history, and every pandemic of influenza has produced a great social burden. We compiled monthly data of influenza incidence from all provinces and autonomous regions in mainland China from January 2004 to December 2011, comprehensively evaluated and classified these data, and then randomly selected 4 provinces with higher incidence (Hebei, Gansu, Guizhou, and Hunan), 2 provinces with median incidence (Tianjin and Henan), 1 province with lower incidence (Shandong), using time series analysis to construct an ARIMA model, which is based on the monthly incidence from 2004 to 2011 as the training set. We exerted the X-12-ARIMA procedure for modeling due to the seasonality these data implied. Autocorrelation function (ACF), partial autocorrelation function (PACF), and automatic model selection were to determine the order of the model parameters. The optimal model was decided by a nonseasonal and seasonal moving average test. Finally, we applied this model to predict the monthly incidence of influenza in 2012 as the test set, and the simulated incidence was compared with the observed incidence to evaluate the model's validity by the criterion of both percentage variability in regression analyses (R) and root mean square error (RMSE). It is conceivable that SARIMA (0,1,1)(0,1,1)12 could simultaneously forecast the influenza incidence of the Hebei Province, Guizhou Province, Henan Province, and Shandong Province; SARIMA (1,0,0)(0,1,1)12 could forecast the influenza incidence in Gansu Province; SARIMA (3,1,1)(0,1,1)12 could forecast the influenza incidence in Tianjin City; and SARIMA (0,1,1)(0,0,1)12 could forecast the influenza incidence in Hunan Province. Time series analysis is a good tool for prediction of disease incidence. PMID- 27367990 TI - CLIF-SOFA score and SIRS are independent prognostic factors in patients with hepatic encephalopathy due to alcoholic liver cirrhosis. AB - Hepatic encephalopathy (HE) is a complication associated with worst prognosis in decompensated liver cirrhosis (LC) patients. Previous studies have identified prognostic factors for HE, and recent studies reported an association between systemic inflammatory response syndrome (SIRS) and liver disease. This study aimed to identify prognostic factors for 30-day mortality in alcoholic LC patients with HE who visited the emergency department (ED).This was a retrospective study of alcoholic LC patients with HE from January 1, 2010, to April 30, 2015. The baseline characteristics, complications of portal hypertension, laboratory values, Child-Pugh class, Model for End-stage Liver Disease (MELD) score, chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score, and SIRS criteria were assessed. The presence of 2 or more SIRS criteria was considered SIRS. The primary outcomes were 30-day mortality and prognostic factors for patients with HE visiting the ED.In total, 105 patients who met the inclusion criteria were analyzed. Overall, the 30-day mortality rate was 6.7% (7 patients).Significant variables were hepatorenal syndrome, international normalized ratio, white blood cell count, total bilirubin level, MELD score CLIF-SOFA score, and SIRS in univariate analysis. CLIF-SOFA score and SIRS were the significant factors in the multivariate analysis (hazard ratio 5.56, 15.98; 95% confidence interval 1.18-26.18, 1.58-161.37; P = 0.03, P = 0.02). The mortality rates differed according to the CLIF-SOFA score (P < 0.01).The CLIF-SOFA score and SIRS in alcoholic LC patients with HE visiting the ED are independent predictors of 30-day mortality. PMID- 27367991 TI - The role of soluble tumor necrosis factor like weak inducer of apoptosis and interleukin-17A in the etiopathogenesis of celiac disease: A cross-sectional study. AB - Our aim in this study was to determine soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) and interleukin-17A (IL-17A) levels in celiac disease, and their association with the gluten diet and autoantibodies. Eighty patients with celiac diagnosis and 80 healthy control individuals with similar age, gender and body mass index to the patient group were included in the study. Serum sTWEAK and IL-17A levels were measured by the serum enzyme-linked immunosorbent assay kit. The median IL-17A (117.5 pg/mL vs. 56.7 pg/mL; P = 0.001) level in celiac patients was higher than in the control group, while the median sTWEAK (543 pg/mL vs. 643 pg/mL; P = 0.016) level in patients was determined to be lower. In the patient group, patients who complied with the gluten diet had a lower level of median IL-17A (98.1 pg/mL vs. 197.5 pg/mL; P = 0.034) and a higher level of sTWEAK (606 pg/mL vs. 522.8 pg/mL; P = 0.031) than those who did not adhere. Furthermore, the IL-17A level was higher and the sTWEAK level was lower in celiac patients with positive antibody than those with negative antibody. A positive correlation was determined among anti-gliadin antibody IgA, anti-gliadin antibody IgG, anti-tissue transglutaminase IgG levels and the IL-17A level, and a negative correlation was determined with the sTWEAK level. In celiac disease, the sTWEAK and IL-17A levels differ between patients who cannot adapt to the gluten diet and who are autoantibody positive, and patients who adapt to the diet and are autoantibody negative. We believe that sTWEAK and IL-17A are associated with the inflammation in celiac pathogenesis. PMID- 27367992 TI - Hepatic resection or transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus. AB - The role of hepatic resection in hepatocellular carcinoma (HCC) with accompanying portal vein tumor thrombus (PVTT) remains controversial. This study aimed to evaluate the surgical outcomes of hepatic resection compared with those of transarterial chemoembolization (TACE) in HCC patients. A retrospective study was conducted using the medical records of 230 HCC patients with portal vein invasion who underwent hepatic resection (96 patients) or TACE (134 patients). The baseline characteristics, tumor characteristics, clinicopathological parameters, and overall survival rates were compared between the 2 groups. The baseline and tumor characteristics were comparable between the hepatic resection and TACE groups. The overall complication rate was 35.4% in the hepatic resection group, which was significantly lower than that in the TACE group (73.0%, P <0.001). However, the serious complication rate (grade >=3) in the hepatic resection group was 13.5%, which was significantly higher than that in the TACE group (P = 0.003). The cumulative overall survival rates at 1, 3, and 5 years in the hepatic resection group were 86.5%, 60.4%, and 33.3%, respectively. These rates were much higher than those in the TACE group (1-year: 77.6%; 3-year: 47.8%; and 5-year: 20.9%; P = 0.021). The long-term survival was notably better in the patients with types I and II PVTT than in the patients with types III and IV PVTT (P <0.05). The univariate and multivariate analyses indicated that types III and IV PVTT and TACE may have contributed to the poor overall survival following surgery. In HCC patients with PVTT and compensated liver function, hepatic resection is a safe and effective surgical protocol, particularly for patients with type I or II PVTT. PMID- 27367993 TI - Analysis of contemporary HIV/AIDS health care costs in Germany: Driving factors and distribution across antiretroviral therapy lines. AB - To analyze contemporary costs of HIV health care and the cost distribution across lines of combination antiretroviral therapy (cART). To identify variations in expenditures with patient characteristics and to identify main cost determinants. To compute cost ratios between patients with varying characteristics.Empirical data on costs are collected in Germany within a 2-year prospective observational noninterventional multicenter study. The database contains information for 1154 HIV-infected patients from 8 medical centers.Means and standard deviations of the total costs are estimated for each cost fraction and across cART lines and regimens. The costs are regressed against various patient characteristics using a generalized linear model. Relative costs are calculated using the resultant coefficients.The average annual total costs (SD) per patient are &OV0556;22,231.03 (8786.13) with a maximum of &OV0556;83,970. cART medication is the major cost fraction (83.8%) with a mean of &OV0556;18,688.62 (5289.48). The major cost-driving factors are cART regimen, CD4-T cell count, cART drug resistance, and concomitant diseases. Viral load, pathology tests, and demographics have no significant impact. Standard non-nucleoside reverse transcriptase inhibitor-based regimens induce 28% lower total costs compared with standard PI/r regimens. Resistance to 3 or more antiretroviral classes induces a significant increase in costs.HIV treatment in Germany continues to be expensive. Majority of costs are attributable to cART. Main cost determinants are CD4-T cells count, comorbidity, genotypic antiviral resistance, and therapy regimen. Combinations of characteristics associated with higher expenditures enhance the increasing effect on the costs and induce high cost cases. PMID- 27367994 TI - Clinicopathologic characteristics, treatment, and outcomes of tubulointerstitial nephritis and uveitis syndrome in adults: A national retrospective strobe compliant study. AB - Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, defined by the association of idiopathic acute TINU. The aim of our work was to determine the characteristics of adult TINU syndrome in France, and to assess factors (including treatment) influencing medium-term prognosis.We conducted a nationwide study including 20 French hospitals. Clinical, laboratory, and renal histopathologic data of 41 biopsy-proven TINU syndromes were retrospectively collected. The patients were diagnosed between January 1, 1999 and December 1, 2015.Twenty-five females and 16 males were included (F/M ratio: 1.6:1). The median age at disease onset was 46.8 years (range 16.8-77.4) with a median serum creatinine level at 207 MUmol/L (range 100-1687) and a median estimated glomerular filtration rate (eGFR) at 27 mL/min per 1.73 m (range 2-73). Twenty nine patients (71%) had a bilateral anterior uveitis and 24 (59%) had deterioration in general health at presentation. Moderate proteinuria was found in 32 patients (78%) (median proteinuria 0.52 g/24 h; range 0.10-2.10), aseptic leukocyturia in 25/36 patients (70%). The evaluation of renal biopsies revealed 41 patients (100%) with an acute tubulointerstitial nephritis, 19/39 patients (49%) with light to moderate fibrosis and 5 patients (12%) with an acute tubular necrosis. Thirty-six patients (88%) were treated with oral corticosteroids. After 1 year of follow-up, the median eGFR was 76 mL/min per 1.73 m (range 17-119) and 32% of the patients suffered from moderate to severe chronic kidney disease. Serum creatinine (P < 0.001, r = -0.54), serum bicarbonate and phosphate levels (respectively, P = 0.01, r = 0.53; and P = 0.04, r = 0.46), and age (P = 0.03, r = -0.37) at the 1st symptoms were associated with eGFR after 1 year. During the 1st year 40% of patients had uveitis relapses. The use of oral corticosteroids was not associated with a better kidney function but was associated with fewer uveitis relapses (P = 0.44 and 0.02, respectively).In our study, 32% of patients were suffering from moderate to severe chronic kidney disease after 1 year of follow-up, and 40% had uveitis relapses during this follow-up. This work also suggests that oral corticosteroids are effective for the treatment of TINU syndrome's uveitis. PMID- 27367995 TI - Does public reporting influence antibiotic and injection prescribing to all patients? A cluster-randomized matched-pair trial in china. AB - The inappropriate use and overuse of antibiotics and injections are serious threats to global population, and the public reporting of health care performance (PRHCP) has been an important instrument for improving the quality of care. However, existing evidence shows a mixed effect of PRHCP. This study is to explore the potential effectiveness of PRHCP that contributes to the convincing evidence of health policy and reform.This study was undertaken in Qian Jiang City, applying a matched-pair cluster-randomized trial. Twenty primary care institutions were treated as clusters and were matched into 10 pairs. Clusters in each pair were randomly assigned into a control or an intervention group. Physicians' prescribing information was publicly reported to patients and physicians monthly in the intervention group from October 2013. A total of 748,632 outpatient prescriptions were included for difference-in-difference (DID) regression model and subgroups (SGs) analysis.Overall, PRHCP intervention led to a slight reduction in the use of combined antibiotics (odds ratio [OR] = 0.870, P < 0.001) and slowed the average expenditure increase of patients (coefficient = 0.051, P < 0.001). SG analysis showed the effect of PRHCP varied among patients with different characteristics. PRHCP decreased the probability of prescriptions requiring antibiotics, combined antibiotics, and injections of patients aged 18 to 64 years old (OR < 1), and all results were statistically significant. By contrast, the results of elderly and minor patients with health insurance showed that PRHCP increased their probability of prescriptions requiring antibiotics and injections. PRHCP slowed the increase of average expenditure of most SGs.PRHCP intervention can influence the prescribing pattern of physicians. Patient factors such as age and health insurance influence the effect of PRHCP intervention, which imply that PRHCP should be designed for different patients. Patient education, aiming at radically changing attitudes toward antibiotics and injections, should be taken to promote the effectiveness of public reporting in China. PMID- 27367996 TI - Nontuberculous mycobacterial pulmonary disease mimicking lung cancer: Clinicoradiologic features and diagnostic implications. AB - To describe the features and clinical implications of computed tomography (CT), positron emission tomography (PET), and percutaneous needle aspiration biopsy (PCNB) in pulmonary nontuberculous mycobacterial (NTM) disease manifesting as a solitary nodule, mass, or mass-like consolidation mimicking malignancy.Among a cohort of 388 patients with NTM pulmonary disease, 14 patients with clinically and radiologically suspected lung cancer were included in our study. Two chest radiologists evaluated CT features, including lesion type (nodule, mass, or mass like consolidation), morphologic features (margin, degree of enhancement, calcification), and presence of accompanying findings suggestive of NTM pulmonary disease (bronchiectasis with clustered centrilobular nodules or upper-lobe cavitary lesions) by consensus. Diagnostic procedures for microbiologic diagnosis of NTM disease and clinical outcome were reviewed.Incidence of NTM pulmonary disease presenting as solitary nodule/mass (n = 8) or mass-like consolidation (n = 6) was 3.6% (14 of 388). Most lesions were detected incidentally during routine health check-up or evaluation of other disease (11 of 14, 79%). Lesions typically showed poor contrast-enhancement (9 of 12) and internal calcification (6 of 14). No lesions had CT features suggestive of NTM pulmonary disease. All 4 lesions for which PET/CT imaging was performed showed strong fluorodeoxyglucose uptake simulating malignant lesions (mean, 4.9; range, 3.6-7.8). PCNB revealed mycobacterial histology in 6 of 11 specimens and positive culture results were obtained for 7 of 7 specimens.NTM pulmonary disease may present as a solitary nodule, mass, or mass-like consolidation mimicking malignancy. CT features and PCNB are important to diagnose NTM disease mimicking lung cancer to avoid unnecessary surgery. PMID- 27367997 TI - Controlled continuous systemic heparinization increases success rate of artery only anastomosis replantation in single distal digit amputation: A retrospective cohort study. AB - Replantation is a prime indication for distal digital amputation, as it helps restore hand aesthetics and functions; however, venous anastomosis is often not feasible. Previous studies used systemic anticoagulation in distal digital artery only anastomosis replantation surgery to improve replantation success rate, however, which yielded limited level of clinical evidence. This study aimed to compare controlled continuous heparinization (CCH) and intermittent bolus heparinization (IBH) for surgical outcome and clinical variables after single distal digital artery only anastomosis replantation surgery.A single-institution, retrospective cohort study was performed. Out of 324 patients who underwent digital replantation surgery, we focused the study for the Zone I and II single distal digital amputation patients excluding confounding factors. Sixty-one patients were included in this study and underwent artery-only anastomosis replantation surgery with postoperative CCH (34 patients) or IBH (27 patients) protocols. The CCH group targeted activated partial thromboplastin time (aPTT) at 51 to 70 seconds, monitoring aPTT levels every eight hours and administering 100 mg of aspirin per day. The IBH group received 300 mg of aspirin per day and underwent IBH (12,500 U). Both groups received intravenous prostaglandin E1 drips (10 MUg). To verify the factors affecting the success rate of the heparin protocol, patient factors, clinical factors, and operative factors were extracted from the medical records. Statistical analysis with inverse probability of treatment weights propensity score methods compared treatment outcomes and clinical variables.The CCH group's replantation success rate was higher (91.17% vs 59.25%), and the transfusion rate was increased (P = 0.032). However, the significant decrease in hemoglobin levels (>15%) did not differ between the groups (P = 0.108). Multivariable logistic regression analysis with potent univariate variables (P < .10) revealed that CCH was a statistically significant variable in replantation success rate (P = 0.004). Neither the major bleeding complications nor the significant decrease in patients' platelet levels were observed in both groups.Our study suggests that CCH after artery-only anastomosis replantation surgery in Zone I and II distal digital replantation is a safe method to improve the replantation success rate and may provide a guideline for use of the anticoagulation method following artery-only anastomosis distal digital replantation surgery. PMID- 27367998 TI - Recovery 3 and 12 months after hysterectomy: epidemiology and predictors of chronic pain, physical functioning, and global surgical recovery. AB - Chronic postsurgical pain (CPSP) is 1 important aspect of surgical recovery. To improve perioperative care and postoperative recovery knowledge on predictors of impaired recovery is essential. The aim of this study is to assess predictors and epidemiological data of CPSP, physical functioning (SF-36PF, 0-100), and global surgical recovery (global surgical recovery index, 0-100%) 3 and 12 months after hysterectomy for benign indication.A prospective multicenter cohort study was performed. Sociodemographic, somatic, and psychosocial data were assessed in the week before surgery, postoperatively up to day 4, and at 3- and 12-month follow up. Generalized linear model (CPSP) and linear-mixed model analyses (SF-36PF and global surgical recovery index) were used. Baseline data of 468 patients were collected, 412 (88%) patients provided data for 3-month evaluation and 376 (80%) patients for 12-month evaluation.After 3 and 12 months, prevalence of CPSP (numeric rating scale >= 4, scale 0-10) was 10.2% and 9.0%, respectively, SF-36PF means (SD) were 83.5 (20.0) and 85.9 (20.2), global surgical recovery index 88.1% (15.6) and 93.3% (13.4). Neuropathic pain was reported by 20 (5.0%) patients at 3 months and 14 (3.9%) patients at 12 months. Preoperative pain, surgery-related worries, acute postsurgical pain on day 4, and surgery-related infection were significant predictors of CPSP. Baseline level, participating center, general psychological robustness, indication, acute postsurgical pain, and surgery related infection were significant predictors of SF-36PF. Predictors of global surgical recovery were baseline expectations, surgery-related worries, American Society of Anesthesiologists classification, type of anesthesia, acute postsurgical pain, and surgery-related infection.Several predictors were identified for CPSP, physical functioning, and global surgical recovery. Some of the identified factors are modifiable and optimization of patients' preoperative pain status and psychological condition as well as reduction of acute postsurgical pain and surgery-related infection may lead to improvement of outcome. PMID- 27367999 TI - Learning curve for single-incision laparoscopic resection of right-sided colon cancer by complete mesocolic excision. AB - Single-incision laparoscopic surgery is cosmetically beneficial, but technically challenging. In this study, the learning curve (LC) for single-incision laparoscopic right hemicolectomy (SILRC), incorporating complete mesocolic excision to resect right-sided colon cancer, was investigated through multidimensional techniques. Between December 2009 and May 2015, 64 patients each underwent SILRC of right-sided colon cancer at Severance Hospital, performed in all instances by the same surgeon. Moving average and cumulative sum control chart (CUSUM) were used for LC analyses retrospectively. Surgical failure was defined as conversion to conventional laparoscopic surgery, postsurgical morbidity within 30 days, harvested lymph node count <12, or local tumor recurrence. Both moving average and CUSUM graphics of operative time registered nadirs at the 24th patient, with slight ascent thereafter, reaching a plateau at the 40th patient. The CUSUM for surgical success peaked at the 23rd patient. Operative time for 23 patients in phase 1 (1-23) and for 41 patients in phase 2 (24-64) of the LC did not differ significantly. By comparison, significant differences in patients of phase 2 included larger tumor size, higher harvested lymph node counts, longer proximal resection margins, and more advanced disease. As indicated by multidimensional statistical analyses, the LC for SILRC of right sided colon cancer was 23 patients. In terms of operative time and surgical success, SILRC is feasible for surgeons experienced in LS, but may prove more challenging for novices, given the fundamental technical difficulties of this procedure. PMID- 27368000 TI - Efficacy of oral ketamine compared to midazolam for sedation of children undergoing laceration repair: A double-blind, randomized, controlled trial. AB - OBJECTIVE: To assess the efficacy of oral ketamine versus oral midazolam for sedation during laceration repair at a pediatric emergency department. METHODS: Children between 1 and 10 years requiring laceration repair were randomly assigned to 2 groups, treated either with oral midazolam (0.7 mg/kg) or with oral ketamine (5 mg/kg).Main outcomes measured were level of pain during local anesthesia, as assessed by the parent on a 10-cm visual analog scale (VAS) and the number of children who required intravenous sedation. Secondary outcomes included VAS by physician, pain assessment by child, maximal sedation depth assessed by the University of Michigan Sedation Scale, time until University of Michigan Sedation Scale 2 or more, general satisfaction of a parent and treating physician, length of procedure, total sedation time, and the incidence of any adverse events. RESULTS: Sixty-eight children were recruited of which 33 were girls. Average age was 5.08 +/- 2.14 years. Thirty-seven children were treated with ketamine and 31 with midazolam. Parent-assessed VAS in ketamine treated patients was 5.07 +/- 0.75 compared with 3.68 +/- 0.7 in midazolam treated patients [mean difference = 1.39 95% confidence interval (CI) -0.47 to 3.26]. Twelve (32%) of the children treated with ketamine required the addition of IV sedation compared to only 2 children (6%) of the children treated with midazolam [odds ratio (adjusted for age and gender) 6.1, 95% CI: 1.2 to 30.5]. The rest of the measured variables were similar between the groups, with no statistical significance. DISCUSSION: No difference in the level of pain was found between ketamine and midazolam treated patients. Compared with oral midazolam (0.7 mg/kg), oral ketamine (5 mg/kg) was associated with higher rates of sedation failure, and thus is not recommended as a single agent for oral sedation in children requiring laceration repair. PMID- 27368001 TI - Primary cellulitis and cutaneous abscess caused by Yersinia enterocolitica in an immunocompetent host: A case report and literature review. AB - Primary extraintestinal complications caused by Yersinia enterocolitica are extremely rare, especially in the form of skin and soft-tissue manifestations, and little is known about their clinical characteristics and treatments. We presented our case and reviewed past cases of primary skin and soft-tissue infections caused by Y enterocolitica. We report a case of primary cellulitis and cutaneous abscess caused by Y enterocolitica in an immunocompetent 70-year-old woman with keratodermia tylodes palmaris progressiva. She presented to an outpatient clinic with redness, swelling, and pain of the left ring finger and left upper arm without fever or gastrointestinal symptoms 3 days before admission. One day later, ulceration of the skin with exposed bone of the proximal interphalangeal joint of the left ring finger developed, and cefditoren pivoxil was described. However, she was admitted to our hospital due to deterioration of symptoms involving the left finger and upper arm. Cefazolin was initiated on admission, then changed to sulbactam/ampicillin and vancomycin with debridement of the left ring finger and drainage of the left upper arm abscess. Wound culture grew Y enterocolitica serotype O:8 and methicillin-sensitive Staphylococcus aureus. Blood cultures were negative and osteomyelitis was ruled out. Vancomycin was switched to ciprofloxacin, then skin and soft-tissue manifestations showed clear improvement within a few days. The patient received 14 days of ciprofloxacin and oral amoxicillin/clavulanate and has since shown no recurrence. We reviewed 12 cases of primary skin and soft-tissue infections caused by Y enterocolitica from the literature. In several past cases, portal entry involved failure of the skin barrier on distal body parts. Thereafter, infection might have spread to the regional lymph nodes from the ruptured skin. Y enterocolitica is typically resistant to aminopenicillins and narrow-spectrum cephalosporins. In most cases, these inefficient antibiotic agents were initially prescribed, but patient conditions rapidly improved after implementing appropriate therapy and drainage. In addition, primary skin and soft-tissue infections occurred even in patients lacking risk factors. Physicians should consider the rare differential diagnosis of Y enterocolitica infection when seeing patients with deteriorating skin lesions under standard treatment, even if the patient is immunocompetent. PMID- 27368002 TI - The content of mutant EGFR DNA correlates with response to EGFR-TKIs in lung adenocarcinoma patients with common EGFR mutations. AB - This study aimed to elucidate the association of the content of mutant epidermal growth factor receptor (EGFR) deoxyribonucleic acid (DNA) with the treatment response to EGFR-tyrosine kinase inhibitor (TKI) and survival in patients with lung cancer.This retrospective cohort study included 77 lung adenocarcinoma patients with common EGFR mutations from December 2012 to February 2015. The content of mutant EGFR DNA in lung cancer tissues was determined using an Amplification Refractory Mutation System. The association of the amount of mutant EGFR DNA with treatment response, the clinical variables, and the progression free survival (PFS) after EGFR-TKI therapy were evaluated.Using the amount of mutant EGR DNA above 4.77% as the cut-off value, the sensitivity to predict EGFR TKI responder is 82.0% and the specificity is 75.0% (area under the curve [AUC]: 0.734, P = 0.003). The high content of mutant EGFR DNA is an independent factor associated with the response to EGFR-TKIs (odds ratio: 13.07, 95% confidence interval [CI]: 3.23-52.11, P = 0.0003). A significantly longer PFS was observed in the group with the high content of mutant EGFR DNA (26.3 months, 95% CI: 12.2 26.3) compared with the low content of mutant EGFR DNA groups (12.3 months, 95% CI: 5.7-14.8, P = 0.0155). A better predictive value of the content of mutant EGFR DNA was noted in patients with exon 19 deletions (AUC: 0.892, P < 0.0001) than exon 21 L858R mutations (AUC: 0.675, P = 0.0856).Our results show that the content of mutant EGFR DNA is associated with the clinical response to EGFR-TKIs, especially in patients with exon 19 deletions mutation. PMID- 27368003 TI - Role of p53 isoforms and aggregations in cancer. AB - p53 is a master regulatory protein that is involved in diverse cellular metabolic processes such as apoptosis, DNA repair, and cell cycle arrest. The protective function of p53 (in its homotetrameric form) as a tumor suppressor is lost in more than 50% of human cancers.Despite considerable experimental evidence suggesting the presence of multiple p53 states, it has been difficult to correlate the status of p53 with cancer response to treatments and clinical outcomes, which suggest the importance of complex but essential p53 regulatory pathways.Recent studies have indicated that the expression pattern of p53 isoforms may play a crucial role in regulating normal and cancer cell fates in response to diverse stresses. The human TP53 gene encodes at least 12 p53 isoforms, which are produced in normal tissue through alternative initiation of translation, usage of alternative promoters, and alternative splicing. Furthermore, some researchers have suggested that the formation of mutant p53 aggregates may be associated with cancer pathogenesis due to loss-of function (LoF), dominant-negative (DN), and gain-of function (GoF) effects.As different isoforms or the aggregation state of p53 may influence tumorigenesis, this review aims to examine the correlation of p53 isoforms and aggregation with cancer. PMID- 27368004 TI - One-year adherence to oral antihyperglycemic medication and risk prediction of patient outcomes for adults with diabetes mellitus: An observational study. AB - Medication adherence is essential in preventing adverse intermediate outcomes, but little is known on hard outcomes. The aims of this study were to determine the 1-year adherence to oral antihyperglycemic drugs (OADs) and to predict the risk of subsequent health outcomes among (non)adherent patients with diabetes.Using a large Swiss healthcare claims database from 2011 to 2014, we identified all patients aged >=18 years with diabetes and treated with at least 1 OAD prescription. Adherence to OADs was measured as the proportion of days covered (PDC) over 1 year and subdivided into 2 categories: adherent (PDC >= 80%), nonadherent (PDC < 80%). We estimated the relative risk of hospitalization and mortality at follow-up using multivariate Cox proportional hazard models.Based on a sample of 26,713 patients, adherence to OADs was quite low: 42% of the patients achieved a PDC of >=80% during the 1-year observation period. A 7% reduction in the hospitalization risk and a 10% reduction in the risk of mortality could be observed in adherent patients compared to nonadherent patients (hazard ratio [HR], 0.93 [95% CI, 0.89-0.97]; HR, 0.90 [95% CI, 0.82-0.99]). Subgroup analysis showed that an intensified diabetes therapy had no significant influence on the risk of both outcomes in adherent patients.Poor medication adherence increases the risk of subsequent hospitalizations and premature mortality in patient with diabetes, regardless of disease severity and comorbidities. This emphasizes the need for an earlier identification of patients with poor medication adherence. The awareness of physicians and patients regarding the importance of adherence in diabetes treatment should be increased. PMID- 27368005 TI - Comparative effectiveness of incretin-based therapies and the risk of death and cardiovascular events in 38,233 metformin monotherapy users. AB - There is limited comparative effectiveness evidence to guide approaches to managing diabetes in individuals failing metformin monotherapy. Our aim was to compare the incidence of all-cause mortality and major adverse cardiovascular events (MACEs) among new metformin monotherapy users initiating a dipeptidyl peptidase-4 inhibitor (DPP4i), glucagon-like peptide-1 receptor agonist (GLP 1RA), sulfonylurea (SU), thiazolidinedione, or insulin.We conducted a cohort study using the UK-based Clinical Practice Research Datalink. Participants included a cohort of 38,233 new users of metformin monotherapy who initiated a 2nd antidiabetic agent between January 1, 2007 and December 31, 2012 with follow up until death, disenrollment, therapy discontinuation, or study end-date. A subcohort of 21,848 patients with linked hospital episode statistics (HES) and Office of National Statistics (ONS) data were studied to include MACE and cardiovascular-related death. The primary exposure contrasts, defined a priori, were initiation of a DPP4i versus an SU and initiation of a GLP-1RA versus an SU following metformin monotherapy. Cox proportional hazards models were used to assess the relative differences in time to mortality and MACE between exposure contrasts, adjusting for important baseline patient factors and comedications used during follow-up.The main study cohort consisted of 6213 (16%) patients who initiated a DPP4i, 25,916 initiated an SU (68%), 4437 (12%) initiated a TZD, 487 (1%) initiated a GLP-1RA, 804 (2%) initiated insulin, and 376 (1%) initiated a miscellaneous agent as their 2nd antidiabetic agent. Mean age was 62 years, 59% were male, and mean glycated hemoglobin was 8.8% (92.6 mmol/mol). Median follow up was 2.7 years (interquartile range 1.3-4.2). Mortality rates were 8.2 deaths/1000 person-years for DPP4i and 19.1 deaths/1000 person-years for SU initiators. Adjusted hazards ratio (aHR) for mortality in DPP4i versus SU initiators = 0.58, 95% CI 0.46 to 0.73, P < 0.001. MACE rates were 19.1/1000 person-years for DPP4i initiators, 15.9/1000 person-years for GLP1-RA initiators versus 33.1/1000 person-years for SU initiators (aHR: DPP4i vs SU initiators = 0.64, 95%CI 0.52-0.80; GLP1RA vs SU initiators = 0.73, 95% CI 0.34-1.55).In this cohort of metformin monotherapy users, 2nd-line DPP4i use was associated with a 42% relative reduction in all-cause mortality and 36% reduction in MACE versus SUs, the most common 2nd-line therapy in our study. GLP-1RAs were not associated with adverse events in this cohort. PMID- 27368006 TI - Pleural LDH as a prognostic marker in adenocarcinoma lung with malignant pleural effusion. AB - To study the performance of serum and pleural lactate dehydrogenase (LDH) level in predicting survival in patients with adenocarcinoma lung presenting with malignant pleural effusions (MPE) at initial diagnosis.Retrospective cohort study of the patient hospitalized for adenocarcinoma lung with MPE in year 2012.Univariate analyses showed lower pleural fluid LDH 667 (313-967) versus 971 (214-3800), P = 0.04, female gender 9 (100%) versus 27 (41.5%), P = 0.009, never smoking status 9 (100%) versus 36 (55.3%), P = 0.009, and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy 8 (89%) versus 26 (40%), P = 0.009 to correlate with survival of more than 1.7 year versus less than 1.7 year. In multivariate analysis, low pleural fluid LDH and female gender maintained significance. The pleural LDH level of <=1500 and >1500 U/L discriminated significantly (P = 0.009) between survival.High pleural LDH (>1500 IU/L) predicts shorter survival (less than a year) in patients with adenocarcinoma lung presenting with MPE at the time of initial diagnosis. This marker may be clinically applied for selecting therapeutic modality directed at prevention of reaccumulation of MPE. Patients with low pleural LDH may be considered suitable for measures that provide more sustained effect on prevention of reaccumulation such as chemical pleurodesis or tunneled pleural catheter. PMID- 27368007 TI - Early analysis of surrogate endpoints for metastatic melanoma in immune checkpoint inhibitor trials. AB - Recent major phase III trials led to the approval of immune checkpoint inhibitors (ipilimumab, pembrolizumab, and nivolumab) in metastatic malignant melanoma (MM). We aim to assess whether median progression-free survival, and 1 and 2-year overall survival (OS) rates are reliable surrogate endpoints for median OS through a meta-analysis of published trials involving immunotherapy. A systematic literature search in PubMed, EMBASE, Web of Science, and SCOPUS of published phase II to III trials with immunotherapy as the treatment for MM was conducted. Adjusted weighted linear regression was used to calculate Pearson correlations (R) between surrogates and median OS, and between treatment effects on surrogates and median OS. A total of 13 studies involving 3373 patients with MM were identified. The correlation of progression-free survival with OS was not significant (R = 0.45, P = .11). Conversely, the correlation between 1-year OS and median OS was very strong (R = 0.93, 95% confidence interval [CI] 0.84-0.96, P < .00001), as was the correlation between 2-year OS and OS (R = 0.79, 95% CI 0.51-0.91, P = .0001). The correlation between the treatment effects on 1-year OS and OS was also significant (R = -0.86, 95% CI -0.3 to 0.97, P = .01). Similar results were obtained for 2-year OS. According to the available study data, 1 year OS rate could be regarded as a potential surrogate for median OS in novel immunotherapy trials of metastatic MM. Waiting for ongoing studies (e.g., pembrolizumab), we suggest that this intermediate endpoint could be considered as a potential primary endpoint in future clinical trials. PMID- 27368008 TI - Increased incidence of rheumatoid arthritis in multiple sclerosis: A nationwide cohort study. AB - Past studies have shown inconsistent results on whether there is an association between multiple sclerosis (MS) and rheumatoid arthritis. To investigate the possible relationship between the 2 autoimmune diseases, we performed a nationwide cohort study utilizing the National Health Insurance Research Database and the Registry of Catastrophic Illness.A total of 1456 newly diagnosed patients with MS and 10,362 control patients were matched for age, sex, and initial diagnosis date. Patients with MS had a higher incidence of rheumatoid arthritis (age-adjusted standardized incidence ratio: 1.72; 95% confidence interval = 1.01 2.91). There was a positive correlation in being diagnosed with rheumatoid arthritis in patients previously diagnosed with MS when stratified by sex and age. The strength of this association remained statistically significant after adjusting for sex, age, and smoking history (hazard ratio: 1.78, 95% confidence interval = 1.24-2.56, P = 0.002).In conclusion, this study demonstrates that a diagnosis of MS increased the likelihood of a subsequent diagnosis of rheumatoid arthritis in patients, independent of sex, age, and smoking history. PMID- 27368009 TI - Retrospective cohort evaluation on risk of pneumonia in patients with pulmonary tuberculosis. AB - Pulmonary tuberculosis (PTb) and pneumonia are diseases that may exist concomitantly. Population study investigating the subsequent pneumonia development in PTb patients is limited. This study compares the risk of pneumonia between cohorts with and without PTb.We used the claims data of the Taiwan National Health Insurance to identify a cohort with PTb (N = 3417) newly diagnosed in 2000-2006 without pneumonia history, and a randomly selected comparison cohort (N = 6834) free of PTb and pneumonia, frequency matched by propensity score. Incidence rates and hazard ratios of pneumonia were calculated by sex, age, and comorbidity starting in the 7th month after the cohorts being established until the end of 2011.We found the incidence of pneumonia to be 1.9 fold higher in the PTb cohort than in the PTb free cohort (51.6 vs 27.0 per 1000 person-years). The PTb cohort had a Cox method estimated adjusted hazard ratio of 2.14 (95% confidence interval = 1.96-2.32). We also found that the risk was greater for men than for women, but lower for young adults aged 20-39 years. Comorbidity interacted with PTb by aggravating the pneumonia risk, particularly for those with asthma. For PTb patients comorbid with asthma, the pneumonia incidence was 2.5-fold higher than for PTb patients free of comorbidities (75.9 vs 29.3 per 1000 person-years).Our results display that PTb patients have an elevated risk of developing pneumonia. Adequate follow-up should be provided to the PTb patients, especially those with comorbidity. PMID- 27368010 TI - Therapeutic approach to IgG4-related disease: A systematic review. AB - To review the reported evidence on the therapeutic management of IgG4-related disease (IgG4-RD) in clinical practice.A systematic search of the literature was conducted. The primary outcome measured was the rate of efficacy of first-line therapeutic approaches. Secondary outcomes measured included the rate of disease relapse, the outcome of untreated patients, the rate of patients without drug therapy at the end of follow-up, the rate of side effects, and mortality. The MOOSE, AHRQ, STROBE, and GRACE recommendations/statements were followed.The results of the systematic search strategy yielded 62 studies that included a total of 3034 patients. Complete information about first-line therapeutic regimens was detailed in 1952 patients, including glucocorticoid-based regimens in 1437 (74%), drug-free regimens in 213 (11%), and other therapies in 38 (2%). No therapy (wait and see management) was reported in 264 (13%) patients. The efficacy of monotherapy with glucocorticoids was specified in 1220 patients, of whom 97% had a therapeutic response. Relapses, however, were reported in 464/1395 (33%) patients despite typically short follow-up periods. Therapeutic efficacy was reported in 219/231 (95%) of relapses treated with glucocorticoids, 56/69 (81%) of those treated with azathioprine, 16/22 (72%) of those treated with other immunosuppressive agents, and in the 9 cases treated with rituximab (100%). In 14 studies, the authors detailed the outcome of 159/246 patients with wait-and-see management; spontaneous improvement or resolution was reported in 68 (43%) cases. Wide heterogeneity was observed with respect to the first-line therapeutic approaches used for the different organ-specific disease subsets, including significant differences in the mean dose of glucocorticoids used.Nearly 70% of reported IgG4-RD patients are treated with oral glucocorticoids in monotherapy. However, the therapeutic management is heavily influenced by geographical, epidemiological, and clinical factors, especially with respect to the predominant organ affected. The frequency of glucocorticoid failure to induce sustained remissions both during and after treatment and the assessment of glucocorticoid toxicity in IgG4-RD require further study. PMID- 27368011 TI - CT findings in viral lower respiratory tract infections caused by parainfluenza virus, influenza virus and respiratory syncytial virus. AB - Viral lower respiratory tract infections (LRTIs) can present with a variety of computed tomography (CT) findings. However, identifying the contribution of a particular virus to CT findings is challenging due to concomitant infections and the limited data on the CT findings in viral LRTIs. We therefore investigate the CT findings in different pure viral LRTIs.All patients who underwent bronchoalveolar lavage (BAL) and were diagnosed with LRTIs caused by parainfluenza virus (PIV), influenza virus, or respiratory syncytial virus (RSV) between 1998 and 2014 were enrolled in a tertiary hospital in Seoul, South Korea. A pure viral LRTI was defined as a positive viral culture from BAL without any positive evidence from respiratory or blood cultures, or from polymerase chain reaction (PCR), or from serologic tests for bacteria, fungi, mycobacteria, or other viruses.CT images of 40 patients with viral LRTIs were analyzed: 14 with PIV, 14 with influenza virus, and 12 with RSV. Patch consolidation (>=1 cm or more than 1 segmental level) was found only in PIV (29%) (P = 0.03), by which CT findings caused by PIV could resemble those seen in bacterial LRTIs. Ground-glass opacities were seen in all cases of influenza virus and were more frequent than in PIV (71%) and RSV (67%) (P = 0.05). Bronchial wall thickening was more common in influenza virus (71%) and RSV (67%) LRTIs than PIV LRTIs (21%) (P = 0.02). With respect to anatomical distribution, PIV infections generally affected the lower lobes (69%), while influenza virus mostly caused diffuse changes throughout the lungs (57%), and RSV frequently formed localized patterns in the upper and mid lobes (44%).The CT findings in LRTIs of PIV, influenza virus, and RSV can be distinguished by certain characteristics. These differences could be useful for early differentiation of these viral LRTIs, and empirical use of appropriate antiviral agents. PMID- 27368012 TI - Double-low protocol for hepatic dynamic CT scan: Effect of low tube voltage and low-dose iodine contrast agent on image quality. AB - The radiation-induced carcinogenesis from computed tomography (CT) and iodine contrast agent induced nephropathy has attracted international attention. The reduction of the radiation dose and iodine intake in CT scan is always a direction for researchers to strive. The purpose of this study was to evaluate the feasibility of a "double-low" (i.e., low tube voltage and low-dose iodine contrast agent) scanning protocol for dynamic hepatic CT with the adaptive statistical iterative reconstruction (ASIR) in patients with a body mass index (BMI) of 18.5 to 27.9 kg/m.A total of 128 consecutive patients with a BMI between 18.5 and 27.9 kg/m were randomly assigned into 3 groups according to tube voltage, iodine contrast agent, and reconstruction algorithms. Group A (the "double-low" protocol): 100 kVp tube voltage with 40% ASIR, iodixanol at 270 mg I/mL, group B: 120 kVp tube voltage with filtered back projection (FBP), iodixanol at 270 mg I/ mL, and group C: 120 kVp tube voltage with FBP, ioversol at 350 mg I/ mL.The volume CT dose index (CTDIvol) and effective dose (ED) in group A were lower than those in group B and C (all P < 0.01). The iodine intake in group A was decreased by approximately 26.5% than group C, whereas no statistical difference was observed between group A and B (P > 0.05). There was no significant difference of the CT values between group A and C (P > 0.05), which both showed higher CT values than that in group B (P < 0.001). However, no statistic difference was observed in the contrast-to-noise ratio (CNR), the signal-to-noise ratio (SNR), and image-quality scores among the 3 groups (all P > 0.05). Near-perfect consistency of the evaluation for group A, B, and C (Kenall's W = 0.921, 0.874, and 0.949, respectively) was obtained by the 4 readers with respect to the overall image quality.These results suggested that the "double low" protocol with ASIR algorithm for multi-phase hepatic CT scan can dramatically decrease radiation dose and iodine intake with adequate image quality in patients with BMI of 18.5 to 27.9 kg/m. PMID- 27368013 TI - Severe hyponatremia caused by nab-paclitaxel-induced syndrome of inappropriate antidiuretic hormone secretion: A case report in a patient with metastatic pancreatic adenocarcinoma. AB - Incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing. Most patients have advanced disease at diagnosis and therapeutic options in this setting are limited. Gemcitabine plus nab-paclitaxel regimen was demonstrated to increase survival compared with gemcitabine monotherapy and is therefore indicated as first-line therapy in patients with metastatic PDAC and performance status Eastern Cooperative Oncology Group (ECOG) 0-2. The safety profile of gemcitabine and nab-paclitaxel combination includes neutropenia, fatigue, and neuropathy as most common adverse events of grade 3 or higher. No case of severe hyponatremia associated with the use of nab-paclitaxel for the treatment of PDAC has been reported to date.We report the case of a 72-year-old Caucasian man with a metastatic PDAC treated with gemcitabine and nab-paclitaxel regimen, who presented with a severe hyponatremia (grade 4) caused by a documented syndrome of inappropriate antidiuretic hormone secretion (SIADH). This SIADH was attributed to nab-paclitaxel after a rigorous imputability analysis, including a rechallenge procedure with dose reduction. After dose and schedule adjustment, nab-paclitaxel was pursued without recurrence of severe hyponatremia and with maintained efficacy.Hyponatremia is a rare but potentially severe complication of nab paclitaxel therapy that medical oncologists and gastroenterologists should be aware of. Nab-paclitaxel-induced hyponatremia is manageable upon dose and schedule adaptation, and should not contraindicate careful nab-paclitaxel reintroduction. This is of particular interest for a disease in which the therapeutic options are limited. PMID- 27368014 TI - Infective endocarditis in hypertrophic cardiomyopathy: A multicenter, prospective, cohort study. AB - Infective endocarditis (IE) complicating hypertrophic cardiomyopathy (HCM) is a poorly known entity. Although current guidelines do not recommend IE antibiotic prophylaxis (IEAP) in HCM, controversy remains.This study sought to describe the clinical course of a large series of IE HCM and to compare IE in HCM patients with IE patients with and without an indication for IEAP.Data from the GAMES IE registry involving 27 Spanish hospitals were analyzed. From January 2008 to December 2013, 2000 consecutive IE patients were prospectively included in the registry. Eleven IE HCM additional cases from before 2008 were also studied. Clinical, microbiological, and echocardiographic characteristics were analyzed in IE HCM patients (n = 34) and in IE HCM reported in literature (n = 84). Patients with nondevice IE (n = 1807) were classified into 3 groups: group 1, HCM with native-valve IE (n = 26); group 2, patients with IEAP indication (n = 696); group 3, patients with no IEAP indication (n = 1085). IE episode and 1-year follow-up data were gathered.One-year mortality in IE HCM was 42% in our study and 22% in the literature. IE was more frequent, although not exclusive, in obstructive HCM (59% and 74%, respectively). Group 1 exhibited more IE predisposing factors than groups 2 and 3 (62% vs 40% vs 50%, P < 0.01), and more previous dental procedures (23% vs 6% vs 8%, P < 0.01). Furthermore, Group 1 experienced a higher incidence of Streptococcus infections than Group 2 (39% vs 22%, P < 0.01) and similar to Group 3 (39% vs 30%, P = 0.34). Overall mortality was similar among groups (42% vs 36% vs 35%, P = 0.64).IE occurs in HCM patients with and without obstruction. Mortality of IE HCM is high but similar to patients with and without IEAP indication. Predisposing factors, previous dental procedures, and streptococcal infection are higher in IE HCM, suggesting that HCM patients could benefit from IEAP. PMID- 27368015 TI - Cerebral ischemic events in patients with pancreatic cancer: A retrospective cohort study of 17 patients and a literature review. AB - Stroke is a dramatic complication of pancreatic cancer with mechanisms related to oncological disease. A better description of the characteristics of cerebrovascular events would help better understand the pathogeny and protect vulnerable patients. We thus conducted a descriptive analysis of clinical, biological, and radiological features of patients from our centers and literature.We reviewed consecutive cases of patients who presented cerebrovascular events and pancreatic cancer in 4 stroke units in Lorrain (France) between January 1, 2009 and March 31, 2015, and all reported cases of literature. We identified 17 cases in our centers and 18 reported cases. Fifty seven per cent of patients were male. Median age was 63 +/- 14 years and ranged from 23 to 81 years. All cerebral events were ischemic. At the onset of stroke, pancreatic cancer had already been diagnosed in 59% of the patients in our centers for a mean time of 5.4 months. Five of them (29%) were being treated with gemcitabine and 2 (12%) with folfirinox. Adenocarcinoma at metastatic stage was reported in 82% of cases overall. Brain imaging revealed disseminated infarctions in 64%. High median levels of D-dimer (7600 +/- 5 * 10 MUg/L), C-reactive protein (63 +/- 43 mg/L), and elevated prothrombin time (19 +/- 6 seconds) were found. Thirty-six per cent of patients explored with echocardiography were diagnosed with nonbacterial thrombotic endocarditis. Ten of our patients received anticoagulant therapy as secondary stroke prevention without any documented recurrence. Nevertheless, outcome was poor with a median survival time of 28 +/- 14 days after stroke onset. Cerebral ischemic events occur at advanced stages of pancreatic cancer, most likely by a thromboembolic mechanism. Disseminated infarctions and high D-dimer, C-reactive protein levels, and a high prothrombin time are the most constant characteristics found in this context. All patients should be screened for nonbacterial thrombotic endocarditis as this etiology supports the use of anticoagulant therapy. PMID- 27368017 TI - Role of galectin-3 and plasma B type-natriuretic peptide in predicting prognosis in discharged chronic heart failure patients. AB - Galectin-3 demonstrated to be a robust independent marker of cardiovascular mid term (18-month) outcome in heart failure (HF) patients. The objective of this study was to analyze the value of a predischarged determination of plasma galectin-3 alone and with plasma brain natriuretic peptide (BNP) in predicting mid-term outcome in frequent-flyers (FF) HF (>=2 hospitalization for HF/year)/dead patients discharged after an acute decompensated HF (ADHF) episode.All FF chronic HF subjects discharged alive after an ADHF were enrolled. All patients underwent a determination of BNP and galectin-3, a 6-minute walk test, and an echocardiogram within 48 hours upon hospital discharge. Death by any cause, cardiac transplantation, and worsening HF requiring readmission to hospital were considered cardiovascular events.Eighty-three patients (67 males, age 73.2 +/- 8.6 years old) were analyzed (mean follow-up 11.6 +/- 5.2 months; range 4-22 months). During the follow-up 38 events (45.7%) were scheduled: (13 cardiac deaths, 35 rehospitalizations for ADHF). According to medical history, in 33 patients (39.8%) a definition of FF HF patients was performed (range 2-4 hospitalization/year). HF patients who suffered an event (FF or death) demonstrated more impaired ventricular function (P = 0.037), higher plasma BNP (P = 0.005), and Gal-3 at predischarge evaluation (P = 0.027). Choosing adequate cut off points (BNP >= 500 pg/mL and Gal-3 >= 17.6 ng/mL), the Kaplan-Meier curves depicted the powerful stratification using BNP + Gal-3 in predicting clinical course at mid-term follow-up (log rank 5.65; P = 0.017).Adding Gal-3 to BNP, a single predischarge strategy testing seemed to obtain a satisfactorily predictive value in alive HF patients discharged after an ADHF episode. PMID- 27368016 TI - Interleukin-10 -1082 G/A gene polymorphisms in Egyptian children with CAP: A case control study. AB - Community-acquired pneumonia (CAP) is one of the leading causes of death worldwide. Cytokines are involved in the pathogenesis of CAP. To date, only a few studies concerned the association of interleukin-10 (IL-10) gene polymorphisms with CAP.In this study, we aimed to investigate whether the -1082(G/A) polymorphism in the promoter region of the IL-10 gene is involved in susceptibility to and the outcome of CAP, and we also measured the serum level of IL-10 to assess its relation to such polymorphism.This was a case-control study included 100 patients with CAP, and matched with age, gender, and ethnicity of 100 healthy control children. IL-10 -1082(G/A) gene polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism, while the serum IL-10 levels were measured by ELISA method.Compared to the controls subjects, the frequencies of the IL-10 -1082 AA genotype and A allele were observed to be overrepresented in patients with CAP (51%; odds ratio [OR] = 2.8; 95% confidence interval [CI]: 1.5-5.3 for the AA genotype; P < 0.01) and (70%; OR: 1.95; 95% CI: 1.27-3.00 for the A allele; P < 0.01, respectively). We found that patients with the GG genotype had significantly higher serum IL-10 levels (46.7 +/- 9.5 pg/mL) compared to those with AG genotype (21.8 +/- 4.5 pg/mL) and AA genotype (11.5 +/- 3.3 pg/mL); P < 0.01, respectively. Our data revealed a significant positive association between the -1082 GG genotype and susceptibility to severe sepsis, acute respiratory failure, and hospital mortality (OR: 3.8; 95% CI: 1.3-11.2; P < 0.01).We demonstrate for the first time, to the best of our knowledge, that IL-10 -1082 (G/A) gene polymorphism may contribute to susceptibility to CAP in Egyptian children. Moreover, we observed that the presence of a G allele or GG genotype at the -1082 position of the promoter region of the IL-10 gene constitute risk factors for developing severe sepsis, acute respiratory failure, and hospital mortality among patients with CAP. PMID- 27368018 TI - Appendectomy correlates with increased risk of pyogenic liver abscess: A population-based cohort study in Taiwan. AB - Little is known on the association between appendectomy and pyogenic liver abscess. The objective of this study was to investigate the association between appendectomy and the risk of pyogenic liver abscess in Taiwan.This population based retrospective cohort study was conducted using the hospitalization dataset of the Taiwan National Health Insurance Program. There were 212,530 subjects age 20 to 84 years with newly diagnosed appendectomy as the appendectomy group since 1998 to 2010, and 850,099 randomly selected subjects without appendectomy as the nonappendectomy group. Both appendectomy and nonappendectomy groups were matched with sex, age, comorbidities, and index year of diagnosing appendectomy. The incidence of pyogenic liver abscess at the end of 2011 was estimated in both groups. The multivariable Cox proportional hazards regression model was applied to investigate the hazard ratio (HR) and 95% confidence interval (CI) for risk of pyogenic liver abscess associated with appendectomy and other comorbidities including alcoholism, biliary stone, chronic kidney disease, chronic liver diseases, and diabetes mellitus.The overall incidence of pyogenic liver abscess was 1.73-fold greater in the appendectomy group than that in the nonappendectomy group (3.85 vs 2.22 per 10,000 person-years, 95% CI 1.71, 1.76). The multivariable regression analysis disclosed that the adjusted HR of pyogenic liver abscess was 1.77 for the appendectomy group (95% CI 1.59, 1.97), when compared with the nonappendectomy group.Appendectomy is associated with increased hazard of pyogenic liver abscess. Further studies remain necessary to confirm our findings. PMID- 27368019 TI - Association between psychiatric disorders and osteoarthritis: a nationwide longitudinal population-based study. AB - Although the association between depressive disorders and osteoarthritis (OA) has been studied, the association of other psychiatric disorders with OA remains unclear. Here, we investigated whether psychiatric disorders are risk factors for OA.The data were obtained from the Longitudinal Health Insurance Database 2005 of Taiwan. We collected the ambulatory care claim records of patients who were diagnosed with psychiatric disorders according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes between January 1, 2004 and December 31, 2008. The prevalence and adjusted hazard ratios (HRs) of osteoarthritis among patients with psychiatric disorders and the control cohort were estimated.Of 74,393 patients with psychiatric disorders, 16,261 developed OA during the 7-year follow-up period. The crude HR for OA was 1.44 (95% confidence interval [CI], 1.39-1.49), which was higher than that of the control cohort. The adjusted HR for OA was 1.42 (95% CI, 1.39-1.42) among patients with psychiatric disorders during the 7-year follow-up period. Further analysis revealed that affective psychoses, neurotic illnesses or personality disorders, alcohol and drug dependence or abuse, and other mental disorders were risk factors for OA.This large-scale longitudinal population-based study revealed that affective psychoses, personality disorders, and alcohol and drug dependence or abuse are risk factors for OA. PMID- 27368020 TI - Relation between injury of the periaqueductal gray and central pain in patients with mild traumatic brain injury: Observational study. AB - The periaqueductal gray (PAG) plays a pivotal role in pain modulation. We attempted to examine the relation between injury of the PAG and central pain in patients with mild traumatic brain injury (TBI).Sixty-one patients with mild TBI with central pain and 31 healthy control subjects were recruited for this study. Visual analog scale (VAS) was used for evaluation of central pain. The region of interest was defined for the PAG and the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured.The FA value was significantly lower in the patient group than in the control group (P < 0.05). However, no significant difference in the ADC value was observed between the patient and control groups (P > 0.05). VAS score of the patient group showed significant moderate negative correlation with the FA (r = -0.38), while no significant correlation was observed between VAS score and the ADC value (P < 0.05).We demonstrated injury of the PAG in patients with central pain following mild TBI and the degree of injury of the PAG was closely related to the degree of central pain. PMID- 27368021 TI - Radiofrequency thermocoagulation for V2/V3 idiopathic trigeminal neuralgia: effect of treatment temperatures on long-term clinical outcomes: A Cohort Study. AB - Radiofrequency thermocoagulation (RFT) is widely used to treat trigeminal neuralgia (TN); however, the optimal temperature at which RFT is most efficacious remains under much debate. Thus, the aim of the present study was to determine the lowest temperature at which morbidity could be minimized and patient outcomes maximized.A multivariate analysis was used to study 1354 patients who underwent computed tomography (CT)-guided RFT for V2/V3 idiopathic trigeminal neuralgia (ITN) during from June 2006 to May 2015. RFT was carried out at 62, 65, and 68 degrees C, while keeping all other RF parameters the same. This was a prospective cohort study, in which we assessed intra- and postoperative complications, pain relief, and long-term health-related quality of life (HRQoL).The intraoperative and in-hospital complications of patients were mainly facial hematoma, mouth and external auditory meatus penetration, nausea, vomiting, dizziness, and headache, which were all treated symptomatically. In long-term follow-up, patients with pain relief (defined as no pain and no required drug intervention) at 62, 65, and 68 degrees C accounted for 94.2%, 98.3%, and 98.8% (at discharge); 83.8%, 90.1%, and 91.4% (at 1 year); 66.7%, 80.5%, and 88.2% (at 3 years); 59.0%, 64.3%, and 77.2% (at 5 years); 48.7%, 57.8%, and 72.3% (at 7 years); 40.6%, 53.7%, and 60.3% (at 9 years), respectively. The number of patients with facial numbness, masticatory atonia, or corneal hypoesthesia was increased with the elevation of temperature, but these complications were all mild. No blindness, deafness, intracranial hemorrhage, or death as a result of the surgical intervention occurred in any patients. SF-36 scores showed highest HRQoL in the group treated at 68 degrees C, followed by the 65 and 62 degrees C groups, respectively.Our results demonstrate that 68 degrees C is a good choice for RFT of V2/V3 ITN. The alternative option is 65 or 62 degrees C for RFT to minimize the occurrence of complications including facial numbness, yet which often yields a higher recurrence rate. PMID- 27368022 TI - Spontaneous remission of membranous glomerulonephritis with successful fetal outcome: A case report and literature review. AB - Membranous glomerulonephritis (MGN) represents an immunologically mediated disease characterized by deposition of immune complexes in the glomerular subepithelial space. Persistent proteinuria at diagnosis predicts poor prognosis. Pregnancy with MGN is a risk of fetal loss and may worsen maternal renal function.Here, we report a lady with MGN and proteinuria achieved spontaneous remission and successful fetal outcome naive to any medications. The 26-year old woman had 1-year history of persistent proteinuria (5.5-12.56 g/24 hours) and biopsy-proven MGN. Histopathological characteristics included glomerular basement membrane spikes, subepithelial monoclonal IgG immunofluorescence, and diffuse electron dense deposits. She was sticking to a regular morning exercise routine without any medications. After successful delivery of a full-term baby girl, the mother had improved proteinuria (0.56 g/24 hours) and albuminuria (351.96 g/24 hours contrasting 2281.6 g/24 hours before pregnancy). The baby had normal height and body weight at 4 months old.We identified more pregnancies with MGN in 5 case reports and 5 clinical series review articles (7-33 cases included). Spontaneous remission of maternal MGN with good fetal outcome rarely occurred in mothers on immunosuppressive therapy.Mothers naive to immunosuppressive therapy may achieve spontaneous remission of maternal membranous glomerulonephritis and successful fetal outcome. Theoretically, fetus might donate stem cells to heal mother's kidney. PMID- 27368023 TI - Devastating renal outcome caused by skin infection with methicillin-resistant Staphylococcus aureus: A case report. AB - Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging pathogen that infects the skin and soft tissue. However, there are few reports of renal complications from MRSA involving immunoglobulin (Ig)A-dominated rapidly progressive glomerulonephritis (GN). Favorable renal outcomes from IgA GN are achieved by administering timely therapy. In the present study, we describe the case of a healthy young woman suffering from a cutaneous MRSA infection that initially presented with gross hematuria. Six months after eradicating the infection, severe impairment of renal function was noted because of intractable nausea and vomiting. Renal pathology revealed advanced IgA nephropathy with fibrocellular crescent formation. An aggressive treatment plan using immunosuppressants was not adopted because of her irreversible renal pathology, and she was therefore administered maintenance hemodialysis.This instructive case stresses the importance of being aware of the signs of IgA nephropathy post-MRSA infection, such as cutaneous lesions that are mostly painless and accompanied by hematuria and mild proteinuria. If the kidney cannot be salvaged, it will undergo irreversible damage with devastating consequences. PMID- 27368024 TI - Increased risk of osteoporosis in patients with erectile dysfunction: A nationwide population-based cohort study. AB - In this study, we aimed to investigate the risk of osteoporosis in patients with erectile dysfunction (ED) by analyzing data from the Taiwan National Health Insurance Research Database (NHIRD). From the Taiwan NHIRD, we analyzed data on 4460 patients aged >=40 years diagnosed with ED between 1996 and 2010. In total, 17,480 age-matched patients without ED in a 1:4 ratio were randomly selected as the non-ED group. The relationship between ED and the risk of osteoporosis was estimated using Cox proportional hazard regression models. During the follow-up period, 264 patients with ED (5.92%) and 651 patients without ED (3.65%) developed osteoporosis. The overall incidence of osteoporosis was 3.04-fold higher in the ED group than in the non-ED group (9.74 vs 2.47 per 1000 person years) after controlling for covariates. Compared with patients without ED, patients with psychogenic and organic ED were 3.19- and 3.03-fold more likely to develop osteoporosis. Our results indicate that patients with a history of ED, particularly younger men, had a high risk of osteoporosis. Patients with ED should be examined for bone mineral density, and men with osteoporosis should be evaluated for ED. PMID- 27368025 TI - Social isolation and cancer management after the 2011 triple disaster in Fukushima, Japan: A case report of breast cancer with patient and provider delay. AB - Breast cancer patients may present with patient delay or experience provider delay-2 factors which can lead to a late-stage diagnosis and poor prognosis. Mass disasters drastically change social structures, and have the potential to contribute to these delays. However, there is little information available on patient and provider delay related to cancer after disasters. In March 2011, an earthquake, followed by a tsunami and nuclear accident struck Fukushima, Japan. In July 2014, a 59 year-old Japanese widow, living alone, presented to our hospital with a lump and pain in her right breast, which had originally appeared in April 2011 and continuously deteriorated for 3 years and 3 months. She was diagnosed with stage IIIB right breast cancer. Detailed history revealed that she was exposed to social isolation in the aftermath of the disasters due to evacuation of her friends and daughter. Although she regularly saw her general practitioner, she did not disclose her breast symptoms for 1 year and 5 months, at which time she was falsely diagnosed with intercostal neuralgia. She did not seek further medical attention for the breast symptoms for another 1 year and 10 months, despite multiple clinic visits for unrelated reasons. The present disasters, particularly the nuclear disaster, seem to have led to the social isolation of local residents, reducing their opportunities to discuss health concerns with others and seek subsequent medical attention.This case highlights that social isolation may contribute to patient and provider delay in breast cancer patients, as accentuated in this disaster setting. PMID- 27368026 TI - The clinical usefulness of a web-based messaging system between patients with Crohn disease and their physicians. AB - To avoid missing events associated with clinical activity, the authors previously developed a novel, web-based, self-reporting Crohn disease (CD) symptom diary. However, although this diary provided a means of self-checking based on responses to set questions based on Harvey-Bradshaw index scores, it was limited in terms of describing other specific symptoms. Thus, the authors added a space to the questionnaire, which allows patients to send clinicians questions or a description of unpredictable events. The aim of the present study was to assess the clinical usefulness of this messaging system by analyzing patients' messages.The messaging system between patients and their doctors was included in a webpage created for recording patients' symptom diaries (www.cdsd.or.kr). Using this system, patients can send messages easily at any time and doctors can read and respond to these messages immediately using a smart phone or computer. In the present study, the authors retrospectively reviewed 686 messages sent by 152 patients from July 2012 to July 2014 and patient medical records.Mean patient age was 29.0 +/- 11.6 years and the male-to-female ratio was 99:53. Most messages regarded symptoms (381 messages, 55.5%), which was followed by self-reports about general condition (195 messages, 28.4%) and questions about treatment (71 messages, 10.3%). With respect to symptoms, abdominal pain was most common (145 cases, 21.1%) followed by hematochezia (36 cases, 5.2%). Problems about medication were the most frequently associated with treatment (65, 91.5%). Patients above 40 years showed a greater tendency to focus on symptoms and treatment (P = 0.025). The doctor answer rate was 56.3% (n = 386), and based on these responses, an early visit was needed in 28 cases (7.3%).Using this web based messaging system, patients were able to obtain proper advice from their physicians without visiting clinics or searching the Internet, and in addition, 7.3% of messages prompted an early visit. Although longer follow-up is required, this study shows that the devised messaging system provides a clinically relevant communication tool for patients and physicians. PMID- 27368027 TI - A cohort study of relationship between serum calcium levels and cerebral microbleeds (CMBs) in ischemic stroke patients with AF and/or RHD. AB - Calcium is an essential element for life and has cerebroprotective property in stroke patients. Low serum calcium levels were found to be related to large hematoma volumes in intracerebral hemorrhagic patients and hemorrhagic transformation in ischemic stroke patients after thrombolysis. However, their impact on hemorrhage-prone small vessel disease represented by cerebral microbleeds (CMBs) is uncertain. We aim to investigate whether low serum calcium levels are associated with presence and location of CMBs.Ischemic stroke patients with atrial fibrillation (AF) and/or rheumatic heart disease admitted to our hospital were consecutively and prospectively enrolled. Demographic and clinical information were collected and analyzed according to the occurrence and location of CMBs, and levels of serum calcium. We used logistic regression analysis to estimate the multivariable adjusted relationship between serum calcium levels and the presence or location of CMBs.Among the 67 patients (28 males; mean age, 67.3 years) in the final analysis, 39 (58.2%) were found to have CMBs. After adjustment for age, sex, smoking habits, drinking habits, and renal impairment, the presence of CMBs and deep CMBs was, respectively, 4.96- and 4.83-fold higher in patients with lower serum calcium levels (<=2.15 mmol/L) than in patients with higher serum calcium levels.Lower serum calcium levels (<=2.15 mmol/L) are independently associated with the presence of CMBs and deep CMBs in ischemic stroke patients with AF and/or rheumatic heart disease, which should be verified and extended in large cohorts, with other types of stroke patients and the general population. PMID- 27368028 TI - Value of MR histogram analyses for prediction of microvascular invasion of hepatocellular carcinoma. AB - The objective is to explore the value of preoperative magnetic resonance (MR) histogram analyses in predicting microvascular invasion (MVI) of hepatocellular carcinoma (HCC).Fifty-one patients with histologically confirmed HCC who underwent diffusion-weighted and contrast-enhanced MR imaging were included. Histogram analyses were performed and mean, variance, skewness, kurtosis, 1th, 10th, 50th, 90th, and 99th percentiles were derived. Quantitative histogram parameters were compared between HCCs with and without MVI. Receiver operating characteristics (ROC) analyses were generated to compare the diagnostic performance of tumor size, histogram analyses of apparent diffusion coefficient (ADC) maps, and MR enhancement.The mean, 1th, 10th, and 50th percentiles of ADC maps, and the mean, variance. 1th, 10th, 50th, 90th, and 99th percentiles of the portal venous phase (PVP) images were significantly different between the groups with and without MVI (P <0.05), with area under the ROC curves (AUCs) of 0.66 to 0.74 for ADC and 0.76 to 0.88 for PVP. The largest AUC of PVP (1th percentile) showed significantly higher accuracy compared with that of arterial phase (AP) or tumor size (P <0.001).MR histogram analyses-in particular for 1th percentile for PVP images-held promise for prediction of MVI of HCC. PMID- 27368029 TI - Identification of an N staging system that predicts oncologic outcome in resected left-sided pancreatic cancer. AB - In this study, we investigated which N staging system was the most accurate at predicting survival in pancreatic cancer patients.Lymph node (LN) metastasis is known to be one of the important prognostic factors in resected pancreatic cancer. There are several LN evaluation systems to predict oncologic impact.From January 1992 to December 2014, 77 medical records of patients who underwent radical pancreatectomy for left-sided pancreatic cancer were reviewed retrospectively. Clinicopathologic variables including pN stage, total number of retrieved LNs (N-RLN), lymph node ratio (LNR), and absolute number of LN metastases (N-LNmet) were evaluated. Disease-free survival (DFS) and disease specific survival (DSS) were analyzed according to these 4 LN staging systems.In univariate analysis, pN stage (pN0 vs pN1: 17.5 months vs 7.9 months, P = 0.001), LNR (<0.08 vs >=0.08: 17.5 months vs 4.4 months, P < 0.001), and N-LNmet (#N = 0 vs #N = 1 vs #N>=2: 17.5 months vs 11.0 months vs 6.4 months, P = 0.002) had a significant effect on DFS, whereas the pN stage (pN0 vs pN1: 35.3 months vs 16.7 months, P = 0.001), LNR (<0.08 vs >=0.08: 37.1 months vs 15.0 months, P < 0.001), and N-LNmet (#N = 0 vs #N = 1 vs #N>=2: 35.3 months vs 18.4 months vs 16.4 months, P = 0.001) had a significant effect on DSS. In multivariate analysis, N LNmet (#N>=2) was identified as an independent prognostic factor of oncologic outcome (DFS and DSS: Exp (beta) = 2.83, P = 0.001, and Exp (beta) = 3.17, P = 0.001, respectively).Absolute number of lymph node metastases predicted oncologic outcome in resected left-sided pancreatic cancer patients. PMID- 27368030 TI - Dosimetric evaluation of incidental irradiation to the axilla during whole breast radiotherapy for patients with left-sided early breast cancer in the IMRT era. AB - The purpose of this study was to compare the dosimetric parameters for incidental irradiation to the axilla during whole breast radiotherapy (WBRT) with 3 dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT). Twenty left breast cancer patients treated with WBRT after breast conserving surgery (BCS) were enrolled in this study. Remnant breast tissue, 3 levels of the axilla, heart, and lung were delineated. We used 2 different radiotherapy methods: 3D-CRT with field-in-field technique and 7-field fixed-beam IMRT. The target coverage of IMRT was significantly better than that of 3D-CRT (Dmean: 49.72 +/- 0.64 Gy vs 50.24 +/- 0.66 Gy, P < 0.001; V45: 93.19 +/- 1.40% vs 98.59 +/- 0.30%, P < 0.001; V47.5: 86.43 +/- 2.72% vs 95.00 +/- 0.02%, P < 0.001, for 3D-CRT and IMRT, respectively). In the IMRT plan, a lower dose was delivered to a wider region of the heart and lung. Significantly lower axillary irradiation was shown throughout each level of axilla by IMRT compared to 3D-CRT (Dmean for level I: 42.58 +/- 5.31 Gy vs 14.49 +/- 6.91 Gy, P < 0.001; Dmean for level II: 26.25 +/- 10.43 Gy vs 3.41 +/- 3.11 Gy, P < 0.001; Dmean for level III: 6.26 +/- 4.69 Gy vs 1.16 +/- 0.51 Gy, P < 0.001; Dmean for total axilla: 33.9 +/- 6.89 Gy vs 9.96 +/- 5.21 Gy, P < 0.001, for 3D-CRT and IMRT, respectively). In conclusion, the incidental dose delivered to the axilla was significantly lower for IMRT compared to 3D-CRT. Therefore, IMRT, which only includes the breast parenchyma, should be cautiously used in patients with limited positive sentinel lymph nodes and who do not undergo complete axillary lymph node dissection. PMID- 27368031 TI - Atrial fibrillation per se was a major determinant of global left ventricular longitudinal systolic strain. AB - Atrial fibrillation (AF) may cause systolic abnormality via inadequate diastolic filling and tachycardia-induced cardiomyopathy. Global longitudinal strain (GLS) is a very sensitive method for detecting subtle left ventricular systolic dysfunction. Hence, this study aimed to evaluate whether AF patients had a more impaired GLS, AF was a major determinant of GLS, and determine the major correlates of GLS in AF patients.The study included 137 patients with persistent AF and left ventricular ejection fraction (LVEF) above 50% and 137 non-AF patients matched according to age, gender, and LVEF. Comprehensive echocardiography with GLS assessment was performed for all cases.Compared with non-AF patients, AF patients had a more impaired GLS, a larger left atrial volume index, higher transmitral E wave velocity (E), and early diastolic mitral velocity (Ea) (all P < 0.001) but comparable E/Ea. After adjustment for baseline and echocardiographic characteristics, the presence of AF remained significantly associated with impaired GLS (beta = 0.533, P < 0.001). In addition, multivariate analysis of AF patients indicated that faster heart rates and decreased E, Ea, and LVEF were associated with more impaired GLS.This study demonstrated that AF patients had a more impaired GLS than non-AF patients, although LVEF was comparable between the 2 groups. AF was a major determinant of GLS even after adjustment for relevant clinical and echocardiographic parameters. PMID- 27368032 TI - Intermittent nasal carriage with Staphylococcus aureus within a menstrual cycle: Results from a prospective cohort of healthy carriers. AB - Female sex hormones have been related to nasal Staphylococcus aureus carriage in healthy individuals; however, whether nasal staphylococcal carriage varies by menstrual cycle phase remains unknown.We sampled anterior nares of female healthcare workers twice per week for 6 consecutive menstrual cycles. We used mixed-effects Poisson regression models to determine whether intermittent carriage was associated with cycle phases in a given individual. We also performed recurrent event survival analysis to identify host factors linked to incident carriage status.Overall, we collected 754 nasal swabs over 89 consecutive person-cycles from 14 intermittent carriers. In 84 ovulation-defined menstrual cycles (715 swabs), the period prevalence of staphylococcal carriage was 58.7%, 63.1%, and 64.9% in the follicular, periovulatory, and luteal phases, respectively; these differences were not statistically significant after multivariable adjustment and correction for within-person correlation (adjusted relative risk [RR]-periovulatory 0.92, P: 0.30; luteal 1.00, P: 0.98).Using survival analysis, we identified several host factors that were associated with incident loss, gain of colonization, or both. For example, as compared to women aged 20 to 30 years, those aged 30 to 40 years were less likely to losing carriage (hazard ratio [HR]: 0.26, 95% confidence interval [CI]: 0.09, 0.80) but were as likely to regaining carriage (HR: 0.53, 95% CI: 0.21, 1.34). In comparison, being underweight (body mass index [BMI] <18.5) was significantly associated with a higher risk for regaining (HR: 1.95, 95% CI: 1.34, 1.51) and losing (HR: 1.57, 95% CI: 1.16, 2.12) colonization, indicating the alternating tendency for status changes. Personal hygiene behaviors, such as nostril cleansing habit and methods, differentially affected carriers' risk for losing or regaining staphylococcal colonization.Using an intensive sampling scheme, we found that nasal staphylococcal carriage could vary substantially over time in healthy carriers. Yet, such dynamic intraperson changes in carriage status did not depend on menstrual cycle phases but were associated with host age, BMI, and personal hygiene behavior. PMID- 27368033 TI - Recovery of consciousness and an injured ascending reticular activating system in a patient who survived cardiac arrest: A case report. AB - We report on a patient who survived cardiac arrest and showed recovery of consciousness and an injured ARAS at the early stage of hypoxic-ischemic brain injury (HI- BI) for 3 weeks, which was demonstrated by diffusion tensor tractography (DTT).A 52-year-old male patient who had suffered cardiac arrest caused by acute coronary syndrome was resuscitated immediately by a layman and paramedics for ~25 minutes. He was then transferred immediately to the emergency room of a local medical center. When starting rehabilitation at 2 weeks after onset, his consciousness was impaired, with a Glasgow Coma Scale (GCS) score of 8 and Coma Recovery Scale-Revised (GRS-R) score of 8. He underwent comprehensive rehabilitative therapy, including drugs for recovery of consciousness. He recovered well and rapidly so that his consciousness had recovered to full scores in terms of GCS:15 and GRS-R:23 at 5 weeks after onset.The left lower dorsal and right lower ventral ARAS had become thicker on 5-week DTT compared with 2-week DTT (Fig. 1B). Regarding the change of neural connectivity of the thalamic ILN, increased neural connectivity to the basal forebrain and prefrontal cortex was observed in both hemispheres on 5-week DTT compared with 2-week DTT.Recovery of an injured ARAS was demonstrated in a patient who survived cardiac arrest and his consciousness showed rapid and good recovery for 3 weeks at the early stage of HI BI. PMID- 27368034 TI - Short-term starvation with a near-fatal asthma attack induced ketoacidosis in a nondiabetic pregnant woman: A case report. AB - Life-threatening refractory metabolic acidosis due to starvation ketoacidosis is rarely reported, even among nondiabetic pregnant women, and may be overlooked. Furthermore, stressful situations may increase the acidosis severity.In the present case, a nondiabetic multiparous woman was admitted for a near-fatal asthma attack and vomiting during the third trimester of pregnancy. She was intubated and rapidly developed high anion gap metabolic acidosis. We diagnosed the patient with starvation ketoacidosis based on vomiting with concomitant periods of stress during pregnancy and the absence of other causes of high anion gap metabolic acidosis. She responded poorly to standard treatment, although the ketoacidosis and asthma promptly resolved after an emergency caesarean section. The patient and her baby were safely discharged.Short-term starvation, if it occurs during periods of stress and medication, can result in life-threatening ketoacidosis, even among nondiabetic women during the third trimester of pregnancy. Awareness of this condition may facilitate prompt recognition and proactive treatment for dietary and stress control, and emergent interventions may also improve outcomes. PMID- 27368035 TI - Diffuse alveolar damage in a patient with rheumatoid arthritis under prolonged leflunomide treatment: A Case Report and Literature Review. AB - Patients with rheumatoid arthritis (RA) often have pulmonary involvement, and interstitial lung disease (ILD) is the primary manifestation, in which diffuse alveolar damage (DAD) is a rare histopathologic pattern. Leflunomide (LEF) is a frequently prescribed disease-modifying antirheumatic drug for treating RA. LEF related ILD in the form of DAD has been reported in patients with RA, with the duration of LEF treatment before symptom onset ranging from 6 to 1204 days.We present a case of elderly woman with RA under prolonged LEF treatment for >9 years (3291 days), who had acute respiratory failure with the initial presentation of exertional dyspnea, fever, chills, and productive cough for 2 days. The histopathologic result of surgical lung biopsy was compatible with DAD. She was diagnosed as having LEF-related ILD, based on correlated clinical history, compatible histopathologic examination and excluding possible infection after extensive survey.Although the causative role of LEF cannot be confirmed, this case still hints that LEF-related DAD may occur even if LEF has been prescribed for a prolonged period. PMID- 27368036 TI - Reversibility of albuminuria and continuous positive airway pressure compliance in patients of obstructive sleep apnea syndrome. AB - A positive correlation between albuminuria and severity of obstructive sleep apnea syndrome (OSAS) has been demonstrated, as indexed by urine albumin-to creatinine ratios (UACRs). However, the effect of continuous positive airway pressure (CPAP) treatment on albuminuria in OSAS patients has not been established.Sixty subjects, with apnea-hypopnea indices >15 events per hour and no other diagnoses associated with albuminuria, underwent overnight polysomnography for sleep apnea and were examined for UACR at baseline and after 6 months of CPAP therapy. CPAP compliance rates were also recorded.Significant improvement in UACR was found in OSAS patients with good compliance to CPAP treatment after 6 months of therapy (baseline vs 6-month follow-up, 32.0 +/- 9.5 vs 19.2 +/- 6.5 mg/g, respectively, P = 0.007), whereas slight worsening in UACRs was noted in patients with poor compliance to CPAP treatment (baseline vs 6-month follow-up, respectively, 16.7 +/- 4.4 vs 19.1 +/- 6.3 mg/g, respectively, P = 0.39). Change in UACR was significant between poor compliance versus good compliance groups (2.4 +/- 2.7 vs -12.8 +/- 4.4 mg/g, respectively, t = 2.9, P = 0.005). A significant correlation between improvement in UACR and CPAP compliance rates was also noted (Spearman's correlation coefficient: -0.37, P = 0.007). Baseline UACR, good CPAP compliance, and body mass index were independent predictors of changes in UACR.Adequate CPAP treatment improves albuminuria in OSAS patients. In addition to monitoring CPAP adherence and subjective sleepiness, UACR may offer an objective physiological index of CPAP therapeutic effectiveness. PMID- 27368037 TI - Extra-axial isolated cerebral varix misdiagnosed as convexity meningioma: A case report and review of literatures. AB - Isolated cerebral varix is a rare cerebrovascular anomaly, which is easily misdiagnosed as other brain tumors.A 59-year-old female patient with noncontributory medical history presented with headache and insomnia for the last 2 months. Upon admission, her neurological examination was unremarkable. Magnetic resonance imaging revealed a well-demarcated extra medullary mass, 11 * 11 mm in size, within the subdural space at the right frontal lobe. The lesion was initially interpreted as a convexity meningioma. After conducting a craniotomy on the patient, an extra-axial varix was exposed and resected subsequently. The patient's headache was resolved soon after surgery and charged without neurologic sequelae.Extra-axial isolated cerebral varix is mimicking convexity meningioma on MR images and should be considered as a differential diagnosis. The focal erosion in the inner table of the skull could be an important character of extra-axial isolated cerebral varix. An extremely round shape and smooth contour of the lesion was another important character. Isolated cerebral varix is rare vascular lesion that is treated surgically in the case of rupture or compression of adjacent structures. The information obtained with noninvasive imaging techniques should include CTA to make a clinical decision. PMID- 27368038 TI - CYP2C19 loss-of-function alleles are not associated with clinical outcome of clopidogrel therapy in patients treated with newer-generation drug-eluting stents. AB - CYP2C19 loss-of-function (LOF) alleles adversely affect clinical outcome of clopidogrel therapy. Recent introduction of a newer-generation drug-eluting stent (DES) has significantly reduced the occurrence of stent thrombosis.The aim of this study was to evaluate the impact of CYP2C19 LOF alleles on clinical outcome in patients treated with the newer-generation DES.The effects of CYP2C19 genotypes were evaluated on clinical outcome of clopidogrel therapy in 2062 patients treated with percutaneous coronary intervention using either first generation DES (sirolimus- and paclitaxel-eluting stent, n = 1349) or newer generation DES (everolimus- and zotarolimus-eluting stent, n = 713). The primary clinical outcome was major cardiac and cerebrovascular event (MACCE) including cardiac death, nonfatal myocardial infarction, stroke, and stent thrombosis during 1 year of follow-up.CYP2C19 LOF alleles were significantly associated with a higher risk of MACCE in patients treated with first-generation DES (hazard ratio [HR] 2.599, 95% confidence interval [CI] 1.047-6.453; P = 0.034). In contrast, CYP2C19 LOF alleles were not associated with primary outcome in newer generation DES (HR 0.716, 95% CI 0.316-1.622; P = 0.522). In the further multivariate analysis, CYP2C19 LOF alleles were not associated with MACCE in patients receiving newer-generation DES (adjusted HR 0.540, 95% CI 0.226-1.291; P = 0.166), whereas they were demonstrated to be an independent risk factor for MACCE in those implanted with first-generation DES (adjusted HR 3.501, 95% CI 1.194-10.262; P = 0.022).In contradiction to their clinical impact in first generation DES era, CYP2C19 LOF alleles may not affect clinical outcome of clopidogrel therapy in patients treated with newer-generation DES. PMID- 27368039 TI - Association of a high normalized protein catabolic rate and low serum albumin level with carpal tunnel syndrome in hemodialysis patients. AB - Carpal tunnel syndrome (CTS) is the most common mononeuropathy in patients with end-stage renal disease (ESRD). The association between chronic inflammation and CTS in hemodialysis (HD) patients has rarely been investigated. HD patients with a high normalized protein catabolic rate (nPCR) and low serum albumin level likely have adequate nutrition and inflammation. In this study, we assume that a low serum albumin level and high nPCR is associated with CTS in HD patients. We recruited 866 maintenance hemodialysis (MHD) patients and divided them into 4 groups according to their nPCR and serum albumin levels: (1) nPCR <1.2 g/kg/d and serum albumin level <4 g/dL; (2) nPCR >=1.2 g/kg/d and serum albumin level <4 g/dL; (3) nPCR <1.2 g/kg/d and serum albumin level >=4 g/dL; and (4) nPCR >=1.2 g/kg/d and serum albumin level >=4 g/dL. After adjustment for related variables, HD duration and nPCR >=1.2 g/kg/d and serum albumin level <4 g/dL were positively correlated with CTS. By calculating the area under the receiver-operating characteristic curve, we calculated that the nPCR and HD duration cut-off points for obtaining the most favorable Youden index were 1.29 g/kg/d and 7.5 years, respectively. Advance multivariate logistic regression analysis revealed that in MHD patients, nPCR >=1.29 g/kg/d and serum albumin <4 g/dL, and also HD duration >7.5 years were associated with CTS. A high nPCR and low serum albumin level, which likely reflect adequate nutrition and inflammation, were associated with CTS in MHD patients. PMID- 27368040 TI - Predictive factors for hospitalization of nonurgent patients in the emergency department. AB - Nonurgent emergency department (ED) patients are a controversial issue in the era of ED overcrowding. However, a substantial number of post-ED hospitalizations were found, which prompted for investigation and strategy management. The objective of this study is to identify risk factors for predicting the subsequent hospitalization of nonurgent emergency patients. This was a retrospective study of a database of adult nontrauma ED visits in a medical center for a period of 12 months from January 2013 to December 2013. Patient triages as either Taiwan Triage and Acuity Scale (TTAS) level 4 or 5 were considered "nonurgent." Basic demographic data, primary and secondary diagnoses, clinical parameters including blood pressure, heart rate, body temperature, and chief complaint category in TTAS were analyzed to determine if correlation exists between potential predictors and hospitalization in nonurgent patients.A total of 16,499 nonurgent patients were included for study. The overall hospitalization rate was 12.47 % (2058/16,499). In the multiple logistic regression model, patients with characteristics of males (odds ratio, OR = 1.37), age more than 65 years old (OR = 1.56), arrival by ambulance (OR = 2.40), heart rate more than 100/min (OR = 1.47), fever (OR = 2.73), and presented with skin swelling/redness (OR = 4.64) were predictors for hospitalization. The area under receiver-operator calibration curve (AUROC) for the prediction model was 0.70. Nonurgent patients might still be admitted for further care especially in male, the elderly, with more secondary diagnoses, abnormal vital signs, and presented with dermatologic complaints. Using the TTAS acuity level to identify patients for diversion away from the ED is unsafe and will lead to inappropriate refusal of care for many patients requiring hospital treatment. PMID- 27368041 TI - A prospective study of freezing of gait with early Parkinson disease in Chinese patients. AB - This study investigated the risk factors for freezing of gait (FOG) in the early stage of Parkinson disease in China, using a sample of 248 patients who were followed for 3 years. Part III of the Unified Parkinson Disease Rating Scale and the modified Hoehn-Yahr grading scale were used to evaluate the severity of motor symptoms. Nonmotor symptoms were assessed using the Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale (HAMD), and Non-Motor Symptoms Scale (NMSS). The end-point was the presence of FOG at the end of follow-up; patients with FOG were classified as freezers. The risk factors for FOG were analyzed at the end of the first, second, and third years after baseline. There were 40 freezers (16.13%) 1 year later, 98 (39.52%) 2 years later, and 128 (51.61%) 3 years later. FOG 3 years later was associated with the following variables: depression (P = 0.003), older age, living in the countryside, lower education, akinetic-rigid style, lower limbs as site of onset, early use of levodopa, higher daily dose of levodopa, and not using amantadine or selegiline and dopamine receptor agonists (P < 0.001). Early use of amantadine, selegiline, and dopamine receptor agonists was negatively related to FOG (P < 0.001). Binary logistic regression found that FOG was associated with lower education (odds ratio [OR] = 0.012, P < 0.001), akinetic-rigid style (OR = 4.881, P = 0.024), not using dopamine receptor agonists (OR = 4.324, P = 0.035), cognitive disturbances (OR = 0.331, P = 0.007), and sleep disorders (OR = 2.418, P = 0.036). However, the cardiovascular domain of the NMSS (OR = 2.729, P = 0.001) was the only risk factor for FOG 1 year later. Two years later, FOG was associated with mixed style (OR = 0.189, P = 0.005), lower limbs as site of onset (OR = 4.772, P = 0.008), not using dopamine receptor agonists (OR = 0.031, P < 0.001), and the anxiety/somatic domain of the HAMD (OR = 0.596, P = 0.033). Scores at baseline, patients with Parkinson disease were more likely to experience FOG if: they were older, or from the countryside; had an akinetic-rigid style, anxiety, or higher NMSS scores; they used levodopa early or did not use amantadine or selegiline; their lower limbs were the site of onset; or they had more severe motor disability or higher HAMD scores at baseline. PMID- 27368042 TI - Tropheryma whipplei endocarditis in Spain: Case reports of 17 prospective cases. AB - Tropheryma whipplei endocarditis is an uncommon condition with very few series and <90 cases reported in the literature. The aim of the study was to analyze the epidemiological, clinical, and outcome characteristics of 17 cases of T. whipplei endocarditis recruited in our country from a multicentric cohort from 25 Spanish hospitals from the Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis infecciosa en Espana.From a total of 3165 cases included in the cohort, 14.2% were diagnosed of blood culture negative endocarditis (BCNE) and 3.5% of these had T. whipplei endocarditis. This condition was more frequent in men. The average age was 60.3 years. Previous cardiac condition was present in 35.3% of the cases. The main clinical manifestation was cardiac failure (76.5%) while fever was only present in the 35.3%. Ecocardiography showed vegetations in 64.7% of patients. Surgery was performed in all but 1 cases and it allowed the diagnosis when molecular assays were performed. A broad range rRNA 16S polymerase chain reaction was used for first instance in all laboratories and different specific targets for T. whipplei were employed for confirmation. A concomitant Whipple disease was diagnosed in 11.9% of patients. All patients received specific antimicrobial treatment for at least 1 year, with no relapse and complete recovery.T. whipplei endocarditis is an uncommon condition with an atypical presentation that must be considered in the diagnosis of BCNE. The prognosis is very good when an appropriate surgical management and antimicrobial specific treatment is given. PMID- 27368043 TI - Effect of RAAS blockers on adverse clinical outcomes in high CVD risk subjects with atrial fibrillation: A meta-analysis and systematic review of randomized controlled trials. AB - Recent studies have demonstrated that atrial fibrillation significantly increases the risk of adverse clinical outcomes in high cardiovascular disease risk subjects. Application of renin-angiotensin-aldosterone system blockers for prevention of recurrence of atrial fibrillation and adverse clinical outcomes in subjects with atrial fibrillation is a theoretically appealing concept. However, results of clinical trials evaluating the effect of renin-angiotensin-aldosterone blockers on adverse clinical outcomes in high cardiovascular disease risk subjects with atrial fibrillation remain inconclusive.A pooled study of 6 randomized controlled trials assessing the efficacy of renin-angiotensin aldosterone blockers on subjects with atrial fibrillation was performed.A total of 6 randomized controlled trials enrolled a total of 53,510 patients followed for 1 to 5 years. RAAS blockade therapy was associated with 14% reduction in the incidence of heart failure (OR: 0.86, [95%CI: 0.76- 0.97], P=0.018) and 17% reduction in the incidence of CVE (OR: 0.83, [95%CI: 0.70-0.99], P = 0.038). The corresponding decline in absolute risk against heart failure (ARR: 1.4%, [95%CI: 0.2-2.6%], P = 0.018) and CVE (ARR: 3.5%, [95%CI: 0.0-6.9%], P = 0.045) in the AF group was much higher than the non-AF group for heart failure (ARR: 0.4%, [95%CI: 0.0-0.7%], P = 0.057) and CVE (ARR: 1.6%, [95%CI: -0.1% to 3.3%], P = 0.071). No significant effect was noted on all-cause or cardiovascular mortality, stroke, or myocardial infarction.This study suggests that RAAS blockade offers protection against heart failure and cardiovascular events in high cardiovascular disease risk subjects with atrial fibrillation. PMID- 27368044 TI - Pathophysiological and diagnostic implications of cardiac biomarkers and antidiuretic hormone release in distinguishing immersion pulmonary edema from decompression sickness. AB - Immersion pulmonary edema (IPE) is a misdiagnosed environmental illness caused by water immersion, cold, and exertion. IPE occurs typically during SCUBA diving, snorkeling, and swimming. IPE is sometimes associated with myocardial injury and/or loss of consciousness in water, which may be fatal. IPE is thought to involve hemodynamic and cardiovascular disturbances, but its pathophysiology remains largely unclear, which makes IPE prevention difficult. This observational study aimed to document IPE pathogenesis and improve diagnostic reliability, including distinguishing in some conditions IPE from decompression sickness (DCS), another diving-related disorder.Thirty-one patients (19 IPE, 12 DCS) treated at the Hyperbaric Medicine Department (Ste-Anne hospital, Toulon, France; July 2013-June 2014) were recruited into the study. Ten healthy divers were recruited as controls. We tested: (i) copeptin, a surrogate marker for antidiuretic hormone and a stress marker; (ii) ischemia-modified albumin, an ischemia/hypoxia marker; (iii) brain-natriuretic peptide (BNP), a marker of heart failure, and (iv) ultrasensitive-cardiac troponin-I (cTnI), a marker of myocardial ischemia.We found that copeptin and cardiac biomarkers were higher in IPE versus DCS and controls: (i) copeptin: 68% of IPE patients had a high level versus 25% of DCS patients (P < 0.05) (mean +/- standard-deviation: IPE: 53 +/- 61 pmol/L; DCS: 15 +/- 17; controls: 6 +/- 3; IPE versus DCS or controls: P < 0.05); (ii) ischemia-modified albumin: 68% of IPE patients had a high level versus 16% of DCS patients (P < 0.05) (IPE: 123 +/- 25 arbitrary-units; DCS: 84 +/- 25; controls: 94 +/- 7; IPE versus DCS or controls: P < 0.05); (iii) BNP: 53% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 383 +/- 394 ng/L; DCS: 37 +/- 28; controls: 19 +/- 15; IPE versus DCS or controls: P < 0.01); (iv) cTnI: 63% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 0.66 +/- 1.50 MUg/L; DCS: 0.0061 +/- 0.0040; controls: 0.0090 +/- 0.01; IPE versus DCS or controls: P < 0.01). The combined "BNP-cTnI" levels provided most discrimination: all IPE patients, but none of the DCS patients, had elevated levels of either/both of these markers.We propose that antidiuretic hormone acts together with a myocardial ischemic process to promote IPE. Thus, monitoring of antidiuretic hormone and cardiac biomarkers can help to make a quick and reliable diagnosis of IPE. PMID- 27368045 TI - Acupuncture as a primary and independent treatment in the acute phases of sudden sensorineural hearing loss: Case Report. AB - Sudden sensorineural hearing loss (SSHL) is an otological emergency defined as a rapid hearing loss, seriously affects patient's social life. To data, no study has reported the treatment by acupuncture alone in the acute phase. In this report, Acupuncture and Moxibustion therapy of excitation-focus transfer is outlined.The patient was a 26-year-old young woman who had an SSHL coupled with ear fullness. The patient had no past medical history, but she had undergone variable emotions and had a history of excessive noise exposure. The patient refused to receive any medicine especially steroids and hyperbaric oxygen therapy. She just only received acupuncture treatment.Her symptoms and outcome measurements were improved every week and completely recovered after the last week.Even though the article presents a single case and is based on self-reports, there are very clear trends on how patients with SSHL responded to acupuncture treatments. PMID- 27368046 TI - Sentinel node navigation surgery for gastroduodenal neuroendocrine tumors: Two case reports. AB - The percentage of gastroduodenal neuroendocrine tumors (NETs) among all gastroenteropancreatic (GEP) NETs has gradually increased worldwide. Sentinel node navigation surgery (SNNS) has been developed as a personalized approach in the surgical strategy for early gastrointestinal tract cancers. We herein report 2 cases of gastroduodenal NETs treated with SNNS. Technetium-tin colloid including indocyanine green was endoscopically injected into the submucosa around a tumor the day before surgery. Basin dissection including the sentinel nodes (SNs), which were identified by Navigator GPS and near-infrared fluorescence imaging, was performed during laparoscopic surgery. SNs were intraoperatively examined using hematoxylin-eosin (HE) staining.SNs were detected in 2 patients. Lymph node metastasis was intraoperatively identified in 1 of the 2 patients. Consequently, 1 patient with metastatic SNs underwent laparoscopic gastrectomy with lymphadenectomy. Pathological findings identified submucosal NET measuring 6.0 mm * 5.0 mm.Our results suggest that SNNS is a promising surgical tool for detecting subclinical lymph node metastasis in patients with gastroduodenal NETs. PMID- 27368047 TI - Effectiveness of 23-valent pneumococcal polysaccharide vaccine on diabetic elderly. AB - Diabetes mellitus is associated with increased risk of pneumonia, and 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for prevention of pneumonia. However, the effectiveness of PPV23 remains unclear in the older diabetic patients who usually have compromised immune function.We used data extracted from the Taiwanese National Health Insurance Research Database (NHIRD) from 2000 to 2009 to conduct a population-based retrospective cohort study, comparing the incidence of pneumococcal diseases among PPV23-vaccinated and propensity-score matched PPV23-unvaccinated groups in diabetic elderly. The primary outcome was invasive pneumococcal diseases (IPDs), and the secondary outcomes were medical utilization.PPV23-vaccinated group had reduced risks of IPD (adjusted OR: 0.86, 95% CI: 0.78-0.94), respiratory failure (0.84, 0.77-0.93), and shorter length of hospitalization (-1.27 +/- 0.19 days, P value: 0.0012). In flu-vaccinated group, subjects who received PPV23 had reduced risks of IPD, hospitalization, and respiratory failure; had shorter lengths of hospitalization; and less medical costs, than those without receiving PPV23. In not flu-vaccinated group, PPV23 vaccination was associated with reduced risks of IPD and respiratory failure. Receiving both vaccines could bring better protection in IPD, hospitalization, visits of emergency department, and respiratory failure.PPV23 vaccination was effective in prevention of pneumococcal diseases and reduction of medical utilization in diabetic elderly aged 75 and more. Receiving both vaccines resulted in better outcomes than PPV vaccination alone. PMID- 27368048 TI - Risk of skin cancer in patients with diabetes mellitus: A nationwide retrospective cohort study in Taiwan. AB - Increasing evidence suggests that certain types of cancers are more common in people with diabetes mellitus (DM). This study aimed to investigate the risk of skin cancer in patients with DM in Taiwan. In this retrospective cohort study using data from the Taiwan Longitudinal Health Insurance Research Database, the risk of developing overall skin cancer, including nonmelanoma skin cancer (NMSC) and melanoma, was compared by Poisson regression analysis and Cox regression analysis between the DM and non-DM cohorts. The DM cohort with newly diagnosed DM (n = 41,898) and a non-DM cohort were one-to-one matched by age, sex, index date, and comorbidities (coronary artery disease, hyperlipidemia, hypertension, chronic kidney disease, chronic obstructive pulmonary disease, and obesity). Compared with non-DM cohort statistically, for the people with DM aged >=60 years, the incidence rates of overall skin cancer and NMSC were significantly higher (overall: DM/non-DM: number [n] = 99/76, incidence rate ratio [IRR] = 1.44, P = 0.02; NMSC: DM/non-DM: n = 94/66, IRR = 1.57, P = 0.005). By Cox regression analysis, the risk of developing overall skin cancer or NMSC was significantly higher after adjusting for sex, comorbidities, and overall diseases with immunosuppression status (overall: adjusted hazard ratio [AHR] = 1.46, P = 0.01; NMSC: AHR = 1.6, P = 0.003). Other significant risk factors were older males for skin cancer (overall: AHR = 1.68, P = 0.001; NMSC: AHR = 1.59, P = 0.004; melanoma: AHR = 3.25, P = 0.04), chronic obstructive pulmonary disease for NMSC (AHR = 1.44, P = 0.04), and coronary artery disease for melanoma (AHR = 4.22, P = 0.01). The risk of developing melanoma was lower in the DM cohort than in the non DM cohort, but without significance (AHR = 0.56, P = 0.28; DM/non-DM: n = 5/10). The incidence rate and risk of developing overall skin cancer, including NMSC, was significantly higher in older adults with DM. Other significant risk factors for older adults with DM were males for NMSC and melanoma, chronic obstructive pulmonary disease for NMSC, and coronary artery disease for melanoma. PMID- 27368050 TI - Relationship between retinal vascular occlusions and incident cerebrovascular diseases: A systematic review and meta-analysis. AB - Several studies investigating the role of retinal vascular occlusions, on cerebrovascular diseases (CVD) have been reported, but the results are still inconsistent. We therefore sought to evaluate the relationship between retinal vascular occlusions and CVD.We systematically searched the Cochrane Library, PubMed, and ScienceDirect databases through January 31, 2016 for studies evaluating the effect of retinal vascular occlusions on the risk of CVD. Data were abstracted using predefined criteria, and then pooled by RevMan 5.3 software.A total of 9 retrospective studies were included in this meta-analysis. When compared with individuals without retinal vascular occlusions, both individuals with retinal artery occlusion (RAO) (odds ratio [OR] = 2.01, 95% confidence interval [CI]: 1.21-3.34; P = 0.005) and individuals with retinal vein occlusion (RVO) (OR = 1.37, 95% CI: 1.24-1.50; P < 0.00001) had higher risks of developing CVD. Additionally, both individuals with central retinal artery occlusion (CRAO) (OR = 2.00, 95% CI: 1.12-3.56; P = 0.02) and branch retinal artery occlusion (BRAO) (OR = 1.60, 95% CI: 1.03-1.48; P = 0.04) were significantly associated with increased risk of CVD.Published literatures support both RVO and RAO are associated with increased risks of CVD. Further prospective studies are needed to confirm these findings. PMID- 27368049 TI - Is obesity a predisposing factor for free flap failure and complications? Comparison between breast and nonbreast reconstruction: Systematic review and meta-analysis. AB - Obesity is a risk factor for postoperative morbidity in breast reconstruction. Although existing studies about nonbreast reconstruction are limited, previous research has demonstrated that obesity is not an important factor in poor outcomes in nonbreast reconstruction. Our study evaluates the effects of obesity on postoperative morbidity in nonbreast reconstruction in comparison to breast reconstruction. A systematic literature review and meta-analysis was performed using Medline, EMBASE, and Cochrane databases. Obesity was extracted for predictor variables and partial, total loss of flap, and complication were extracted for outcome variables. Subgroup analyses were performed according to reconstruction site. The Newcastle-Ottawa scale (NOS) was used to assess the quality of the studies, and the Cochrane risk of bias tool was used. Publication bias was evaluated using funnel plots. The search strategy identified 944 publications. After screening, 19 articles were selected for review. Partial flap loss, total flap loss, and complications in breast reconstruction occurred significantly more often in obese patients in comparison to nonobese patients (OR = 2.479, P = 0.021 for partial loss, OR = 3.083, P = 0.002 for total loss, OR = 2.666, P = 0.001 for complications). In contrast, partial flap loss, total flap loss, and complications in nonbreast reconstruction were not significantly different in obese patients in comparison to nonobese patients (OR = 0.786, P = 0.629 for partial loss, OR = 0.960, P = 0.961 for total loss, and OR = 1.009, P = 0.536 for complications). In contrast to the relationship between obesity and poor outcomes in breast reconstruction, our study suggests the obesity is not a predisposing factor for poor outcomes in nonbreast reconstruction. Long-term studies are needed to confirm these findings. PMID- 27368051 TI - A predicted model for postoperative seizure outcomes after the surgical resection of supratentorial cavernous malformations. AB - To explore a predicted model for postoperative seizure outcomes after the surgical resection of supratentorial cavernous malformations.This study was a retrospective review of consecutive patients with cerebral supratentorial cavernous malformations presenting with seizures. All patients underwent surgical resection of CCMs. Univariate and multivariate analyses were performed to determine the predictive value of the preoperative seizure frequency, seizure type, seizure duration, lesion location, lesion size, and the presence of residual hemosiderin.A total of 43 patients met the inclusion criteria. After a mean follow-up period of 40.95 months, 34 patients who were free from postoperative seizures were classified into Engel class I, and the remaining 9 patients were classified into Engel classes II-IV. A univariate analysis showed that the seizure frequency (chi = 13.440, P = 0.004) and seizure duration (chi = 5.145, P = 0.023) prior to surgery were associated with a worse postoperative seizure prognosis. Other covariates including age at onset, gender, a history of the medications taken, smoking status, family history, lesion characteristics, and the role of hemosiderin were not related to seizure outcomes. Logistic regression results demonstrated that the preoperative seizure frequency was an effective predictor (P = 0.004). The receiver operating characteristic curve indicated that area under the curve for the preoperative seizure frequency test was 0.833 (95% confidence interval 0.709-0.957, P = 0.002).The preoperative seizure frequency was a prognostic factor for postoperative seizure outcomes after surgical resection of supratentorial cavernous malformations. To obtain a favorable prognosis for CCM patients with preoperative seizures, early intervention might be a better choice. PMID- 27368052 TI - Effect of probiotics on metabolic profiles in type 2 diabetes mellitus: A meta analysis of randomized, controlled trials. AB - Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease which is imposing heavy burden on global health and economy. Recent studies indicate gut microbiota play important role on the pathogenesis and metabolic disturbance of T2DM. As an effective mean of regulating gut microbiota, probiotics are live micro-organisms that are believed to provide a specific health benefit on the host. Whether probiotic supplementation could improve metabolic profiles by modifying gut microbiota in T2DM or not is still in controversy.The aim of the study is to assess the effect of probiotic supplementation on metabolic profiles in T2DM.We searched PubMed, EMBASE, and Cochrane Library up to 12 April 2016. Two review authors independently assessed study eligibility, extracted data, and evaluated risk of bias of included studies. Data were pooled by using the random effect model and expressed as standardized mean difference (SMD) with 95% confidence interval (CI). Heterogeneity was assessed and quantified (I).A total of 12 randomized controlled trials (RCTs) were included. Lipid profiles (n = 508) and fasting blood glucose (FBG) (n = 520) were reported in 9 trials; the homeostasis model of assessment for insulin resistance index (HOMA-IR) (n = 368) and glycosylated hemoglobin (HbA1c) (n = 380) were reported in 6 trials. Probiotics could alleviate FBG (SMD -0.61 mmol/L, 95% CI [-0.92, -0.30], P = 0.0001). Probiotics could increase high-density lipoprotein-cholesterol (HDL-C) (SMD 0.42 mmol/L, 95% CI [0.08, 0.76], P = 0.01). There were no significant differences in low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), HbA1c and HOMA-IR between the treatment group and the control group.Probiotics may improve glycemic control and lipid metabolism in T2DM. Application of probiotic agents might become a new method for glucose management in T2DM. PMID- 27368053 TI - Architecture of fully occupied GluA2 AMPA receptor-TARP complex elucidated by cryo-EM. AB - Fast excitatory neurotransmission in the mammalian central nervous system is largely carried out by AMPA-sensitive ionotropic glutamate receptors. Localized within the postsynaptic density of glutamatergic spines, AMPA receptors are composed of heterotetrameric receptor assemblies associated with auxiliary subunits, the most common of which are transmembrane AMPA receptor regulatory proteins (TARPs). The association of TARPs with AMPA receptors modulates receptor trafficking and the kinetics of receptor gating and pharmacology. Here we report the cryo-electron microscopy (cryo-EM) structure of the homomeric rat GluA2 AMPA receptor saturated with TARP gamma2 subunits, which shows how the TARPs are arranged with four-fold symmetry around the ion channel domain and make extensive interactions with the M1, M2 and M4 transmembrane helices. Poised like partially opened 'hands' underneath the two-fold symmetric ligand-binding domain (LBD) 'clamshells', one pair of TARPs is juxtaposed near the LBD dimer interface, whereas the other pair is near the LBD dimer-dimer interface. The extracellular 'domains' of TARP are positioned to not only modulate LBD clamshell closure, but also affect conformational rearrangements of the LBD layer associated with receptor activation and desensitization, while the TARP transmembrane domains buttress the ion channel pore. PMID- 27368054 TI - Human and Murine Hematopoietic Stem Cell Aging Is Associated with Functional Impairments and Intrinsic Megakaryocytic/Erythroid Bias. AB - Aging within the human hematopoietic system associates with various deficiencies and disease states, including anemia, myeloid neoplasms and reduced adaptive immune responses. Similar phenotypes are observed in mice and have been linked to alterations arising at the hematopoietic stem cell (HSC) level. Such an association is, however, less established in human hematopoiesis and prompted us here to detail characteristics of the most primitive human hematopoietic compartments throughout ontogeny. In addition, we also attempted to interrogate similarities between aging human and murine hematopoiesis. Coupled to the transition from human cord blood (CB) to young and aged bone marrow (BM), we observed a gradual increase in frequency of candidate HSCs. This was accompanied by functional impairments, including decreased lymphoid output and reduced proliferative potential. Downstream of human HSCs, we observed decreasing levels of common lymphoid progenitors (CLPs), and increasing frequencies of megakaryocyte/erythrocyte progenitors (MEPs) with age, which could be linked to changes in lineage-affiliated gene expression patterns in aged human HSCs. These findings were paralleled in mice. Therefore, our data support the notion that age related changes also in human hematopoiesis involve the HSC pool, with a prominent skewing towards the megakaryocytic/erythroid lineages, and suggests conserved mechanisms underlying aging of the blood cell system. PMID- 27368055 TI - Illness Beliefs in End Stage Renal Disease and Associations with Self-Care Modality Choice. AB - BACKGROUND: Interest in self-care haemodialysis (HD) has increased because it improves patients'clinical and quality-of-life outcomes. Patients who undertake self-management for haemodialysis may hold illness beliefs differently to those choosing institutional care at the time of making the modality choice or moulded by their illness and dialysis treatment experience. Illness perceptions amongst predialysis patients and in those undertaking fully-assisted and self-care haemodialysis are being investigated in a combined cross-sectional and longitudinal study. STUDY DESIGN: The study data are derived from the BASIC-HHD study, a multicentre observational study on factors influencing home haemodialysis uptake. 535 patients were enrolled into three groups: Predialysis CKD-5 group, prevalent 'in-centre' HD and self-care HD groups (93% at home). We explore illness perceptions in the cross-sectional analyses of the three study groups, using the revised Illness Perception Questionnaire (IPQ-R). Predialysis patients' illness beliefs were reassessed prospectively, typically between 4 and 12 months after dialysis commencement. RESULTS: Illness belief subscales are significantly different between in-centre and self-care HD groups. In a step-wise hierarchical regression analysis, after adjustment for age, education, marital status, diabetes, dialysis vintage, depression, anxiety scores, and IPQ-R subscales, personal control (p = 0.01) and illness coherence (p = 0.04) are significantly higher in the self-care HD group. In the predialysis group, no significant associations were found between illness representations and modality choices. In prospectively observed predialysis group, scores for personal control, treatment control, timeline cyclical and emotional representations reduced significantly after commencing dialysis and increased significantly for illness coherence. CONCLUSIONS: Illness beliefs differ between hospital and self care haemodialysis patients. Patient's affect and neurocognitive ability may have an important role in determining illness beliefs. The impact of modality upon illness representations may also be significant and remains to be explored. PMID- 27368056 TI - Modelling the Distribution of Forest-Dependent Species in Human-Dominated Landscapes: Patterns for the Pine Marten in Intensively Cultivated Lowlands. AB - In recent years, the "forest-specialist" pine marten Martes martes has been reported to also occur also in largely fragmented, lowland landscapes of north western Italy. The colonization of such an apparently unsuitable area provided the opportunity for investigating pine marten ecological requirements and predicting its potential south- and eastwards expansion. We collected available pine marten occurrence data in the flood plain of the River Po (N Italy) and relate them to 11 environmental variables by developing nine Species Distribution Models. To account for inter-model variability we used average ensemble predictions (EP). EP predicted a total of 482 suitable patches (8.31% of the total study area) for the pine marten. The main factors driving pine marten occurrence in the western River Po plain were the distance from watercourses and the distance from woods. EP suggested that the pine marten may further expand in the western lowland, whilst the negligible residual wood cover of large areas in the central and eastern plain makes the habitat unsuitable for the pine marten, except for some riparian corridors and the pine wood patches bordering the Adriatic coast. Based on our results, conservation strategies should seek to preserve remnant forest patches and enhance the functional connectivity provided by riparian corridors. PMID- 27368057 TI - Comparison of High-Intensity Interval Training and Moderate-to-Vigorous Continuous Training for Cardiometabolic Health and Exercise Enjoyment in Obese Young Women: A Randomized Controlled Trial. AB - OBJECTIVE: The aim of this study was to compare the effects of 5-week high intensity interval training (HIIT) and moderate-to-vigorous intensity continuous training (MVCT) on cardiometabolic health outcomes and enjoyment of exercise in obese young women. METHODS: A randomized controlled experiment was conducted that involved thirty-one obese females (age range of 18-30) randomly assigned to either HIIT or MVCT five-week training programs. Participants in HIIT condition performed 20 min of repeated 8 s cycling interspersed with 12 s rest intervals, and those in MVCT condition cycled continuously for 40 min at 60-80% of peak oxygen consumption ([Formula: see text]O2peak), both for four days in a week. Outcomes such as [Formula: see text]O2peak, body composition estimated by bioimpedance analysis, blood lipids, and serum sexual hormones were measured at pre-and post-training. The scores of Physical Activity Enjoyment Scale (PAES) were collected during the intervention. RESULTS: After training, [Formula: see text]O2peak increased significantly for both training programs (9.1% in HIIT and 10.3% in MVCT) (p = 0.010, eta2 = 0.41). Although MVCT group had a significant reduction in total body weight (TBW, -1.8%, p = 0.034), fat mass (FM, - 4.7%, p = 0.002) and percentage body fat (PBF, -2.9%, p = 0.016), there were no significant between-group differences in the change of the pre- and post-measures of these variables. The HIIT group had a higher score on PAES than the MVCT group during the intervention. For both conditions, exercise training led to a decline in resting testosterone and estradiol levels, but had no significant effect on blood lipids. CONCLUSION: Both HIIT and MVCT are effective in improving cardiorespiratory fitness and in reducing sexual hormones in obese young women; however, HIIT is a more enjoyable and time-efficient strategy. The mild-HIIT protocol seems to be useful for at least maintaining the body weight among sedentary individuals. PMID- 27368058 TI - Neutrophil-to-Lymphocyte Ratio Predicts PSA Response and Prognosis in Prostate Cancer: A Systematic Review and Meta-Analysis. AB - An unprecedented advance has been seen in castration-resistant prostate cancer (CRPC) treatments in the past few years. With a number of novel agents were approved, there is a pressing need to develop improved prognostic biomarkers to facilitate the personalised selection and sequencing of these novel agents. Emerging evidence indicates that the neutrophil-to-lymphocyte ratio (NLR) is associated with poorer survival in patients with prostate cancer (PCa). However, the importance of the NLR for the prediction of the PSA response (PSARS) and biochemical recurrence (BCR) has been largely neglected. Here, we conducted a systematic review and meta-analysis to evaluate the prognostic value of the NLR for the PSARS, BCR, and survival in PCa. A systematic database search was performed using Embase, PubMed, the Cochrane Library, and the China National Knowledge Infrastructure (CNKI). A meta-analysis was performed by pooling hazard ratios (HRs), odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). A total of 22 studies were included in the meta-analysis. Our results suggest that an elevated NLR predicts a lower PSARS rate (OR = 1.69, 95% CI: 1.40 1.98) and a higher possibility of BCR (HR = 1.12, 95% CI: 1.02-1.21). Additionally, we confirmed that an elevated NLR was a prognostic predictor of shorter overall survival (OS) in both metastatic castration-resistant PCa (mCRPC) (HR = 1.45, 95% CI: 1.32-1.59) and localized PCa (LPC) (HR = 1.12, 95% CI: 1.01 1.23) and that it predicted worse progression-free survival (PFS) in CRPC (HR = 1.42, 95% CI: 1.23-1.61) and poorer recurrence-free survival (RFS) (HR = 1.38, 95%CI: 1.01-1.75) in LPC. Our results suggest that an elevated NLR might be employed as a prognostic marker of biochemical changes and prognosis to facilitate risk stratification and decision making for individual treatment of PCa patients. The potential mechanisms underlying these associations and future research directions are also discussed. PMID- 27368059 TI - How Close is too Close? The Effect of a Non-Lethal Electric Shark Deterrent on White Shark Behaviour. AB - Sharks play a vital role in the health of marine ecosystems, but the potential threat that sharks pose to humans is a reminder of our vulnerability when entering the ocean. Personal shark deterrents are being marketed as the solution to mitigate the threat that sharks pose. However, the effectiveness claims of many personal deterrents are based on our knowledge of shark sensory biology rather than robust testing of the devices themselves, as most have not been subjected to independent scientific studies. Therefore, there is a clear need for thorough testing of commercially available shark deterrents to provide the public with recommendations of their effectiveness. Using a modified stereo-camera system, we quantified behavioural interactions between white sharks (Carcharodon carcharias) and a baited target in the presence of a commercially available, personal electric shark deterrent (Shark Shield Freedom7TM). The stereo-camera system enabled an accurate assessment of the behavioural responses of C. carcharias when encountering a non-lethal electric field many times stronger than what they would naturally experience. Upon their first observed encounter, all C. carcharias were repelled at a mean (+/- std. error) proximity of 131 (+/- 10.3) cm, which corresponded to a mean voltage gradient of 9.7 (+/- 0.9) V/m. With each subsequent encounter, their proximity decreased by an average of 11.6 cm, which corresponded to an increase in tolerance to the electric field by an average of 2.6 (+/- 0.5) V/m per encounter. Despite the increase in tolerance, sharks continued to be deterred from interacting for the duration of each trial when in the presence of an active Shark ShieldTM. Furthermore, the findings provide no support to the theory that electric deterrents attract sharks. The results of this study provide quantitative evidence of the effectiveness of a non-lethal electric shark deterrent, its influence on the behaviour of C. carcharias, and an accurate method for testing other shark deterrent technologies. PMID- 27368060 TI - Utility of the multi-component training distress scale to monitor swimmers during periods of training overload. AB - The purpose of the present study was to determine the efficacy of the multi component training distress scale (MTDS), in monitoring swimmers prior to national competition. Twenty-one national-level adolescent swimmers completed eight weeks of testing. Once a week participants completed an 8 * 50 m sprint test, vertical jump test, sit-and-reach test, the MTDS and the Recovery-Stress Questionnaire for Athletes (REST-Q). All testing was incorporated into the swimmers' normal training programme. The REST-Q accounted for the following variances in performance: flexibility (14.6%, p = 0.009), power output (17.7%, p = 0.003), swimming speed (15.5%, p = 0.006) and swimming endurance (17.5%, p = 0.002). In comparison, the MTDS accounted for the following variances in performance: flexibility (12.1%, p = 0.095), power output (16.4%, p = 0.023), swimming speed (20.5%, p = 0.003) and swimming speed endurance (23.8%, p = 0.001). The findings of the current study suggest that both the REST-Q Sport and the MTDS have the capacity to predict performance on a range of fitness components associated with swimming. PMID- 27368061 TI - Computed Tomography Perfusion and Diffusion-Weighted Imaging in Patients With Acute Stroke-Reply. PMID- 27368062 TI - Risk of progression to diabetes from prediabetes defined by HbA1c or fasting plasma glucose criteria in Koreans. AB - AIMS: To examine the abilities of HbA1c and fasting plasma glucose (FPG) criteria predicting 5-year progression rate to diabetes in Korean adults with prediabetes. METHODS: Participants included 17,971 Koreans (aged 20-79years) who underwent routine medical check-ups at a mean interval of 5.2years (3.1-6.7years). Prediabetes was defined as FPG 5.6-6.9mmol/l or HbA1c 5.7-6.4% (39-46mmol/mol). Incident diabetes was defined as FPG?7.0mmol/l, HbA1c?6.5% (48mmol/mol), or initiation of antidiabetic medications. RESULTS: At baseline, the prevalence of prediabetes was 30.6% (n=5495) by FPG and 20.4% (n=3664) by HbA1c criteria. The 5 year progression rate to diabetes was significantly higher in prediabetes identified by HbA1c than by FPG tests (14.7% vs. 10.4%, P<0.001). Of individuals diagnosed with prediabetes by only one test, those by HbA1c alone had a higher risk of progression to diabetes than those diagnosed by FPG alone (6.0% vs. 3.9%, P<0.001). Receiver operating characteristic curve analysis showed that area under the curve was greater for HbA1c (0.855, 95% CI 0.840-0.870) than for FPG (0.830, 0.813-0.846) (P=0.016). After adjustment for conventional risk factors, the odds ratio (OR) of developing diabetes was higher in participants with prediabetes identified by HbA1c (OR 9.91, 8.24-11.9) than by FPG (OR 7.29, 5.97-8.89) (P=0.026). CONCLUSIONS: Although fewer individuals with prediabetes were identified by HbA1c than by FPG criteria, the ability to predict progression to diabetes was stronger for HbA1c than for FPG in Koreans. PMID- 27368063 TI - The effects of hyperventilation on axonal excitability parameters in patients with diabetes mellitus and polyneuropathy. AB - AIMS: We aimed to explore axonal excitability parameters in patients with diabetes mellitus (DM) and polyneuropathy (PNP) as well as those without PNP. METHODS: We used the short TROND protocol by QTRAC to measure axonal excitability parameters (strength-duration time constant (SDTC), rheobase, etc.) in 12 healthy subjects and 14 DM patients with PNP and 10 DM patients without PNP. The short TROND protocol was performed before and after 20min of deep hyperventilation in healthy subjects and patients with DM. Also, venous blood pH and partial pressure of O2 and CO2 were recorded before hyperventilation (HPV) and after 20min of HPV. A "hyperventilation score" was evaluated before and after HPV. RESULTS: When the values of DM with PNP group and control group before HPV were compared, SDTC and latency were statistically significant. Comparing the values of the excitability parameters after HPV showed statistically significant changes in the SDTC, rheobase, and refractoriness at 2.5ms in controls and DM patients without PNP. HPV resulted in no changes in SDTC in DM patients with PNP. CONCLUSION: The results of this study suggest that patients with DM and healthy subjects have different responses to HPV, and pH changes have different effects on diabetic PNP compared with healthy controls and DM patients without PNP. PMID- 27368064 TI - Sarcopenia associated with renal function in the patients with type 2 diabetes. AB - AIMS: Studies have suggested that low muscle mass is associated with declining renal function in healthy populations, whether the association is relevant to patients with type 2 diabetes is not well understood. This study investigates the association between sarcopenia and estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratios (UACR) in the patients with type 2 diabetes. METHODS: Two recruited groups consisted of 793 persons without diabetes (males/females=550/243) and 762 persons with type 2 diabetes (males/females=501/261). RESULTS: The non-sarcopenia population demonstrated higher ASM/HT(2), GFR (P<0.001) and lower UACR (P<0.05) than the sarcopenia population. In studied men, the association between ASM/HT(2) and eGFR was statistically significant in the group without diabetes (OR=0.580, P=0.020), a trend which persisted in women (OR=0.491, P=0.014). The association between ASM/HT(2) and UACR persisted in studied women of two groups (OR=0.269, P=0.005; OR=0.405, P=0.008, respectively). The highest quartile of ASM/HT(2) in the non sarcopenia population exhibited a 3.753-fold risk of abnormal eGFR within the diabetes group (OR=3.753, P=0.020). The cutoff point of ASM/HT(2) to indicate abnormal renal function for population with non-sarcopenia was 6.32kg/m(2) in the group without diabetes and 6.31kg/m(2) in diabetes group. CONCLUSIONS: Sarcopenia is associated with declining renal function, which induces lower eGFR and higher UACR. In the non-sarcopenia population, ASM/HT(2) presents as renal function risk factor, which perhaps associated with higher muscle mass to induce a greater underestimation for creatinine and urinary albumin. PMID- 27368065 TI - Heparin-bridging therapy is associated with a high risk of post-polypectomy bleeding regardless of polyp size. AB - BACKGROUND AND AIM: Evidence regarding safety and efficacy of heparin-bridging therapy for colonoscopic polypectomy remains scarce. The aim of the present study was to evaluate the risk of post-polypectomy bleeding (PPB) in patients receiving heparin-bridging therapy. METHODS: We retrospectively reviewed the database of patients who underwent colonoscopic polypectomy with prophylactic clip closure between January 2007 and December 2014 at our institution. We evaluated patients receiving heparin-bridging therapy (HB group) compared with those who did not receive antithrombotic therapy (No-HB group). RESULTS: A total of 1421 polypectomies were carried out on 773 patients; 45 patients were in the HB group and 728 patients were in the No-HB group. The incidence of PPB per patient was significantly higher in the HB group (22.2% vs 1.9%, P < 0.0001), and multivariate analysis showed that heparin-bridging therapy was an independent risk factor for PPB (OR 9.80, 95% CI 4.23-22.3, P < 0.0001). In the HB group, the polyp size was not a risk factor for PPB (OR 0.67, 95% CI 0.19-2.26, P = 0.55); the incidence of PPB in lesions of <10 mm and >=10 mm in size was 14.6% and 10.2% respectively. In contrast, that was a significant risk factor in the No-HB group (OR 4.71, 95% CI 1.41-21.3, P = 0.011). Activated partial thromboplastin time and international normalized ratio were in or under the therapeutic range in the HB group when PPB occurred. CONCLUSIONS: Heparin-bridging therapy is associated with a high risk of PPB regardless of polyp size. PMID- 27368066 TI - EPR analysis of extra- and intracellular nitric oxide in liver biopsies. AB - PURPOSE: To develop an assay that can enable the quantification of intra- and extracellular nitric oxide (NO) levels in liver biopsies without application of potentially harmful exogenous NO traps. THEORY: Electron paramagnetic resonance (EPR) spectroscopy is currently the most appropriate method of measuring NO in biological samples due to the outstanding specificity resulting from the interaction of NO with exogenous NO traps. Because such traps are not allowed in clinical settings, we tested the reliability of endogenous NO traps for the determination of NO levels in blood and liver compartments. METHODS: Rats were injected with 0-8 mg/kg lipopolysaccharide (LPS) to gradually induce a systemic inflammatory response. Specific features of NO-hemoglobin and NO-Fe EPR signals were quantified using a specifically developed calibration procedure. RESULTS: Whereas both NO-hemoglobin (NO-HbLIVER BLOOD ) and NO-Fe (NO-FeLIVER ) complexes were detected in nonperfused liver tissue, only NO-Fe complexes were detected in perfused tissue and only NO-Hb complexes were detected in blood (NO-HbBLOOD ). The NO concentrations increased in the sequence NO-HbBLOOD < NO-FeLIVER < NO HbLIVER BLOOD (9.4, 18.5, 27.9 nmol/cm3 , respectively at 2.5 mg/kg LPS). The detection limit of the method was 0.61 nmol/cm3 for NO-Hb and 0.52 nmol/cm3 for NO-Fe. CONCLUSION: The assay reported here does not influence natural NO pathways and enables the quantification of NO distribution in two liver compartments using a single liver biopsy. Magn Reson Med 77:2372-2380, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27368067 TI - Results of NCCTG N0275 (Alliance) - a phase II trial evaluating resection followed by adjuvant radiation therapy for patients with desmoplastic melanoma. AB - To examine, in a prospective fashion, the utilization and efficacy of adjuvant radiation therapy (RT) in patients with resected desmoplastic melanoma (DM). Adult patients with resected, margin-negative, and nonmetastatic DM were eligible for this single-arm prospective phase II study. Patients were to receive postoperative RT, 30 Gy in five fractions, to the operative bed with 2- to 3-cm margins (depending on the tumor location). Nodal basin RT was not allowed. The primary study endpoint was the 2-year local recurrence rate (LRR). Secondary endpoints included the incidence of regional and distant metastatic disease, progression-free survival, overall survival (OS), and treatment-related toxicity. Twenty patients with a single de novo DM lesion meeting trial eligibility criteria were enrolled and treated. The 2-year LRR was 10%, with two patients demonstrating a LR within 2 years of completion of protocol therapy. No regional or distant failures occurred. OS at 2 and 5 years was 95 and 77%, respectively. There were no grade 3 or higher acute or late adverse events that were related to the protocol therapy. Adjuvant RT after wide local excision (WLE) for DM is efficacious and well tolerated. It should be considered for DM patients after margin-negative WLE. Additional study is needed to further refine low-risk patient populations that can potentially have adjuvant RT omitted as part of the treatment plan. PMID- 27368068 TI - Transmission of Neurodegenerative Disorders Through Blood Transfusion: A Cohort Study. AB - BACKGROUND: The aggregation of misfolded proteins in the brain occurs in several neurodegenerative disorders. Aberrant protein aggregation is inducible in rodents and primates by intracerebral inoculation. Possible transfusion transmission of neurodegenerative diseases has important public health implications. OBJECTIVE: To investigate possible transfusion transmission of neurodegenerative disorders. DESIGN: Retrospective cohort study. SETTING: Nationwide registers of transfusions in Sweden and Denmark. PARTICIPANTS: 1 465 845 patients who received transfusions between 1968 and 2012. MEASUREMENTS: Multivariable Cox regression models were used to estimate hazard ratios for dementia of any type, Alzheimer disease, and Parkinson disease in patients receiving blood transfusions from donors who were later diagnosed with any of these diseases versus patients who received blood from healthy donors. Whether excess occurrence of neurodegenerative disease occurred among recipients of blood from a subset of donors was also investigated. As a positive control, transmission of chronic hepatitis before and after implementation of hepatitis C virus screening was assessed. RESULTS: Among included patients, 2.9% received a transfusion from a donor diagnosed with one of the studied neurodegenerative diseases. No evidence of transmission of any of these diseases was found, regardless of approach. The hazard ratio for dementia in recipients of blood from donors with dementia versus recipients of blood from healthy donors was 1.04 (95% CI, 0.99 to 1.09). Corresponding estimates for Alzheimer disease and Parkinson disease were 0.99 (CI, 0.85 to 1.15) and 0.94 (CI, 0.78 to 1.14), respectively. Hepatitis transmission was detected before but not after implementation of hepatitis C virus screening. LIMITATION: Observational study design, underascertainment of the outcome, and possible insufficient statistical power. CONCLUSION: The data provide no evidence for the transmission of neurodegenerative diseases and suggest that if transmission does occur, it is rare. PRIMARY FUNDING SOURCE: Swedish Research Council, Swedish Heart-Lung Foundation, Swedish Society for Medical Research, and Danish Council for Independent Research. PMID- 27368069 TI - Instrument for Predicting Early Stroke Recurrence: Ambiguity and Biases-Reply. PMID- 27368070 TI - Effects of exogenously applied hydrogen peroxide on antioxidant and osmoprotectant profiles and the C3-CAM shift in the halophyte Mesembryanthemum crystallinum L. AB - Exogenously applied H2O2 (50, 100 and 200mM) to Mesembryanthemum crystallinum root medium induced a transition from C3 to Crassulacean Acid Metabolism (CAM), as evaluated by diurnal malate (Deltamal) fluctuations. A very high concentration of H2O2 (400mM) reduced Deltamal below the value measured in control plants. An increase of malate content during the night in 400mM H2O2-treated plants might suggest that malate decarboxylation is crucial for CAM functioning. We conclude that malate plays a dual role: i) a protective and signaling function before CAM expression, and ii) a storage form of CO2 in plants performing CAM. A slight stimulation of photosystem II (PSII) photochemistry and net photosynthesis observed during the C3-CAM shift indicated that neither photoinhibition nor reduction of the photosynthetic rate were prerequisites for CAM. Moreover, CAM induction corresponded to a decrease of catalase activity. In CAM-performing plants, alpha-tocopherol, polyamines (putrescine and spermidine) and proline showed daily alterations and the content of alpha-tocopherol and polyamines was lower at the end of the day. In contrast, the proline concentration correlated with the applied H2O2 concentration and was higher at the end of the day in treated plants. The dynamic changes of antioxidant and osmolyte levels suggest their active role in preventing oxidative damage, stress acclimation mechanisms and involvement in metabolic regulation and/or signal transduction cascades. PMID- 27368071 TI - Minimizing photodecomposition of flavin adenine dinucleotide fluorescence by the use of pulsed LEDs. AB - Dynamic alterations in flavin adenine dinucleotide (FAD) fluorescence permit insight into energy metabolism-dependent changes of intramitochondrial redox potential. Monitoring FAD fluorescence in living tissue is impeded by photobleaching, restricting the length of microfluorimetric recordings. In addition, photodecomposition of these essential electron carriers negatively interferes with energy metabolism and viability of the biological specimen. Taking advantage of pulsed LED illumination, here we determined the optimal excitation settings giving the largest fluorescence yield with the lowest photobleaching and interference with metabolism in hippocampal brain slices. The effects of FAD bleaching on energy metabolism and viability were studied by monitoring tissue pO2 , field potentials and changes in extracellular potassium concentration ([K+ ]o ). Photobleaching with continuous illumination consisted of an initial exponential decrease followed by a nearly linear decay. The exponential decay was significantly decelerated with pulsed illumination. Pulse length of 5 ms was sufficient to reach a fluorescence output comparable to continuous illumination, whereas further increasing duration increased photobleaching. Similarly, photobleaching increased with shortening of the interpulse interval. Photobleaching was partially reversible indicating the existence of a transient nonfluorescent flavin derivative. Pulsed illumination decreased FAD photodecomposition, improved slice viability and reproducibility of stimulus-induced FAD, field potential, [K+ ]o and pO2 changes as compared to continuous illumination. PMID- 27368072 TI - Leaf physico-chemical and physiological properties of maize (Zea mays L.) populations from different origins. AB - In this study we evaluated the leaf surface properties of maize populations native to different water availability environments. Leaf surface topography, wettability and gas exchange performance of five maize populations from the Sahara desert, dry (south) and humid (north-western) areas of Spain were analysed. Differences in wettability, stomatal and trichome densities, surface free energy and solubility parameter values were recorded between populations and leaf sides. Leaves from the humid Spanish population with special regard to the abaxial side, were less wettable and less susceptible to polar interactions. The higher wettability and hydrophilicity of Sahara populations with emphasis on the abaxial leaf surfaces, may favour dew deposition and foliar water absorption, hence improving water use efficiency under extremely dry conditions. Compared to the other Saharan populations, the dwarf one had a higher photosynthesis rate suggesting that dwarfism may be a strategy for improving plant tolerance to arid conditions. The results obtained for different maize populations suggest that leaf surfaces may vary in response to drought, but further studies will be required to examine the potential relationship between leaf surface properties and plant stress tolerance. PMID- 27368073 TI - Experimental taphonomy: post-mortem microstructural modifications in Sus scrofa domesticus bone. AB - Bone is a highly specialised form of hard and rigid connective tissue whose histological structure undergoes post-mortem modifications. In taphonomic research, histological examination of bone thin sections is used to investigate these post-mortem microstructural changes in skeletal tissues. In this study, diagenetic modifications in pig skeletal remains (Sus scrofa domesticus) which were exposed to different taphonomic conditions as part of a long-term, real-time experiment were examined under light microscope (i.e. plain and cross polarized light). This experiment demonstrated that macroscopic appearance and microscopic preservation of bone may significantly differ. Early microbial attack was identified as enlarged osteocyte lacunae that later coalesce to constitute larger foci. Additionally, microscopic preservation of different skeletal elements varied intra-individually, while within bone differential preservation (i.e. proximal versus distal ends) was also observed. However, no specific patterns of early histological attack (e.g. endosteal and periosteal destruction) and no clear relationship between histological preservation and proximity to the abdominal area were detected. Lastly, the presence and composition of protective textiles had a clear effect on bone preservation. This research project, therefore, provided important evidence for the better understanding of the diagenetic processes that occur within bones whilst buried or exposed on the ground surface. PMID- 27368075 TI - The Gold Standard for Current Cancer Treatment. PMID- 27368074 TI - Engaging Patients, Health Care Professionals, and Community Members to Improve Preoperative Decision Making for Older Adults Facing High-Risk Surgery. AB - Importance: Older patients are at greater risk for postoperative complications, yet they are less likely than younger patients to ask questions about surgery. Objective: To design an intervention to improve preoperative decision making and manage postoperative expectations. Design, Setting, and Participants: A Patient and Family Advisory Council (PFAC) was created to help identify preoperative decisional needs. The PFAC included 4 men and women who had previous experience with high-risk surgery as older patients or their family members; the PFAC met monthly at a local library from May 2014 to April 2015 to examine findings from a prior qualitative study and to integrate themes with PFAC members' experiences. Patient observations included 91 recorded conversations between patients and surgeons and 61 patient interviews before and after surgery. The PFAC members and other stakeholders evaluated 118 publicly available questions and selected 12 corresponding to identified needs to generate a question prompt list (QPL). Three focus groups, including 31 community members from diverse backgrounds, were conducted at community centers in Madison and Milwaukee, Wisconsin, to refine the QPL. A clinical pilot with 42 patients considering surgery was conducted in one outpatient surgical clinic in Madison. Main Outcomes and Measures: Generation of a QPL to address patients' preoperative informational and decisional needs. Results: Through exploration of qualitative data, the PFAC noted 3 critical problems. Patients and family members believed surgery had to be done, were surprised that postoperative recovery was difficult, and lacked knowledge about the perioperative use of advance directives. The PFAC identified a need for more information and decisional support during preoperative conversations that included clarification of treatment options, setting postoperative expectations, and advance care planning. The following 3 question prompt categories arose: "Should I have surgery?" "What should I expect if everything goes well?" and "What happens if things go wrong?" The final list included 11 questions within these domains, was understandable in English and Spanish, and was acceptable to patients in the clinic. Conclusions and Relevance: Through direct engagement of stakeholders, a QPL was created to address core decisional and informational needs of surgical patients. Future testing will evaluate whether this list can be used to improve patient engagement and reduce postoperative regret and conflict about postoperative treatments. PMID- 27368076 TI - Patterns of Care and Comparative Effectiveness of Intensified Adjuvant Therapy for Resected Oropharyngeal Squamous Cell Carcinoma in the Human Papillomavirus Era. AB - IMPORTANCE: There is a growing debate on the relative benefits of adjuvant chemoradiotherapy (CRT) and boost doses of postoperative radiotherapy (B-PORT) in oropharyngeal squamous cell carcinoma (OPSCC) treated with primary surgery, especially for patients with human papillomavirus (HPV)-driven disease. OBJECTIVE: To characterize the recent patterns of care in and overall survival (OS) outcomes following the use of adjuvant CRT and B-PORT after primary surgery for OPSCC. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of patients in the National Cancer Database with stage III to IVA-B OPSCC treated with surgery and adjuvant radiotherapy between 2010 and 2012 at Commission on Cancer accredited facilities. The data analysis was performed between June 15, 2015, and May 4, 2016. MAIN OUTCOMES AND MEASURES: The primary outcomes were prevalence of CRT and B-PORT, and OS. The primary predictors were HPV positivity and high-risk pathologic features (HRPFs) (extracapsular extension and positive surgical margins). RESULTS: Of the 1409 patients (1153 [82%] male; median age, 57 [interquartile range {IQR}, 51-63] years), 873 (62%) and 789 (56%) patients received CRT and B-PORT, respectively; most patients (n = 583 [79%]) with HRPFs received CRT, and many patients (n = 227 [40%]) without HRPFs received CRT. Multivariable predictors of CRT included adverse pathologic features (extracapsular extension [OR, 6.99; 95% CI, 5.22-9.35], positive surgical margins [OR, 2.07; 95% CI, 1.50-2.87], >=6 involved nodes [OR, 2.34; 95% CI, 1.39-3.92], or low-neck disease [OR, 1.52; 95% CI, 1.01-2.28]), and treatment at a nonacademic institution (OR, 1.59 [95% CI, 1.21-2.10] for comprehensive community cancer center vs academic program). Patients with HPV-positive disease (OR, 0.47; 95% CI, 0.33-0.68) were less likely to receive CRT; this decrease was limited to absent HRPF treated at academic institutions (n = 173, 44 [25%] received CRT). With a median follow-up of surviving patients of 27 (IQR, 21-33) months, the 2 year OS probability was 92% (95% CI, 90%-94%). Multivariable analysis including age, sex, pathologic T stage, 6 or more positive nodes, and educational status confirmed the prognostic impact of HPV positivity (hazard ratio [HR], 0.41; 95% CI, 0.21-0.80) and HRPFs (positive surgical margins [HR, 2.15; 95% CI, 1.27-3.66] and >=6 involved nodes [HR, 2.11; 95% CI, 1.13-3.93]), but neither CRT (HR, 1.27; 95% CI, 0.70-2.30) nor B-PORT (HR, 1.04; 95% CI, 0.63-1.73) was associated with improved OS. CONCLUSIONS AND RELEVANCE: Postoperative CRT and B-PORT following resection of OPSCC were dependent on factors beyond HRPFs, including HPV status and treatment at an academic institution. No benefit was seen with intensified adjuvant therapy, supporting enrollment of the HPV-positive population into deintensification trials. PMID- 27368077 TI - Confocal Microscopy of Corneal Nerves-a Limited but Still Useful Technique to Evaluate Peripheral Neuropathies. PMID- 27368078 TI - Controversies in Inherited Bleeding Disorders. PMID- 27368079 TI - Weak-field H3O+ ion cyclotron resonance alters water refractive index. AB - Heretofore only observed in living systems, we report that weak-field ion cyclotron resonance (ICR) also occurs in inanimate matter. Weak magnetic field (50 nT) hydronium ICR at the field combination (7.84 Hz, 7.5 uT) markedly changes water structure, as evidenced by finding an altered index of refraction exactly at this combined field. This observation utilizes a novel technique which measures the scattering of a He-Ne laser beam as the sample is exposed to a ramped magnetic field frequency. In addition to the hydronium resonance, we find evidence of ICR coupling to a more massive structure, possibly a tetrahedral combination of three waters and a single hydronium ion. To check our observations, we extended this technique to D2O, successfully predicting the specific ICR charge-to-mass ratio for D3O+ that alters the index of refraction. PMID- 27368081 TI - Ligand-induced dependence of charge transfer in nanotube-quantum dot heterostructures. AB - As a model system to probe ligand-dependent charge transfer in complex composite heterostructures, we fabricated double-walled carbon nanotube (DWNT)-CdSe quantum dot (QD) composites. Whereas the average diameter of the QDs probed was kept fixed at ~4.1 nm and the nanotubes analyzed were similarly oxidatively processed, by contrast, the ligands used to mediate the covalent attachment between the QDs and DWNTs were systematically varied to include p-phenylenediamine (PPD), 2 aminoethanethiol (AET), and 4-aminothiophenol (ATP). Herein, we have put forth a unique compilation of complementary data from experiment and theory, including results from transmission electron microscopy (TEM), near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, Raman spectroscopy, electrical transport measurements, and theoretical modeling studies, in order to fundamentally assess the nature of the charge transfer between CdSe QDs and DWNTs, as a function of the structure of various, intervening bridging ligand molecules. Specifically, we correlated evidence of charge transfer as manifested by changes and shifts associated with NEXAFS intensities, Raman peak positions, and threshold voltages both before and after CdSe QD deposition onto the underlying DWNT surface. Importantly, for the first time ever in these types of nanoscale composite systems, we have sought to use theoretical modeling to justify and account for our experimental results. Our overall data suggest that (i) QD coverage density on the DWNTs varies, based upon the different ligand pendant groups used and that (ii) the presence of a pi-conjugated carbon framework within the ligands themselves coupled with the electron affinity of their pendant groups collectively play important roles in the resulting charge transfer from QDs to the underlying CNTs. PMID- 27368082 TI - Unrelenting spread of the alien monk parakeet Myiopsitta monachus in Israel. Is it time to sound the alarm? AB - BACKGROUND: Monk parakeets, Myiopsitta monachus Boddaert, are native to South America but have established populations in North America, Europe, Africa and Asia. They are claimed to act as agricultural pests in their native range, and their communal stick nests may damage human infrastructure. Although several monk parakeet populations are present in the Mediterranean Basin and temperate Europe, little empirical data are available on their population size and growth, distribution and potential impact. We investigated the temporal and spatial dynamics of monk parakeets in Israel to assess their invasion success and potential impact on agriculture. RESULTS: Monk parakeet populations are growing exponentially at a higher rate than that reported elsewhere. The current Israeli population of monk parakeets comprises approximately 1500 individuals. The distribution of the species has increased and shifted from predominantly urban areas to agricultural landscapes. CONCLUSIONS: In Israel, monk parakeet populations are growing fast and have dispersed rapidly from cities to agricultural areas. At present, reports of agricultural damage are scarce. A complete assessment of possible management strategies is urgently needed before the population becomes too large and widespread to allow for cost-effective mitigation campaigns to be implemented. (c) 2016 Society of Chemical Industry. PMID- 27368083 TI - The Bellina-Missoni method and the Morrison technique: two variations of free hand no-adapter smartphone microscopic photography. PMID- 27368084 TI - Pollination by sexual deception-it takes chemistry to work. AB - Semiochemicals are of paramount importance in sexually deceptive plants. These plants sexually lure specific male insects as pollinators by chemical and physical mimicry of the female of the pollinator. The strategy has evolved repeatedly in orchids, with a wide diversity of insect groups exploited. Chemical communication systems confirmed by field bioassays include: alkenes and alkanes in bee pollinated Ophrys species, keto-acid and hydroxy-acids in scoliid wasp pollinated O. speculum, and cyclohexanediones and pyrazines in thynnine wasp pollinated Chiloglottis and Drakaea orchids, respectively. In Ophrys, stearoyl acyl carrier protein desaturase (SAD) enzymes have been confirmed to control species level variation in alkene double bond position. The production of cyclohexanediones in Chiloglottis unexpectedly depends on UVB light, a phenomenon unknown for other plant specialised metabolites. Potential biosynthetic pathways for other systems are explored, and alternative approaches to further accelerate chemical discovery in sexually deceptive plants are proposed. PMID- 27368085 TI - Trauma- and Stress-Induced Response in Veterans with Alcohol Dependence and Comorbid Post-Traumatic Stress Disorder. AB - BACKGROUND: Alcohol dependence (AD) and post-traumatic stress disorder (PTSD) commonly co-occur, and the co-occurrence is associated with worse prognosis than either disorder absent the other. Craving is an important construct related to relapse, but the relationship between PTSD symptoms, craving, and relapse is not well understood. Several studies have documented the relationship between stress and craving in individuals without comorbid PTSD, but the effect on those with comorbid PTSD is not well known. A small literature suggests that trauma imagery affects craving. This is the first study to explore the effects of trauma-induced and stress-induced scripts on alcohol craving, affect, cardiovascular, and cortisol responses in the laboratory. METHODS: Veterans (n = 25) diagnosed with AD and PTSD who were participating in a randomized clinical treatment trial took part in this laboratory study. Baseline assessment included PTSD symptoms and drinking quantity and frequency over 3 months before study initiation. In the laboratory, participants were exposed to neutral, stressful, and trauma scripts randomly assigned. Main outcomes included craving, anxiety, mood states, salivary cortisol, and cardiovascular responses. RESULTS: Both stress and trauma scripts produced greater increases in craving, negative affect, and cardiovascular reactivity, compared to neutral scripts. Trauma scripts produced significantly stronger craving for alcohol and greater cardiovascular reactivity than stress scripts. Also, trauma-induced but not stress-induced craving was positively correlated with baseline levels of drinking. There were no changes in cortisol levels from pre- to postexposure of any scripts. CONCLUSIONS: The results highlight that trauma cues are more salient in inducing alcohol craving than stress cues and higher reactivity is related to more baseline drinking. This finding is consistent with clinical observations that show an association between PTSD symptoms and alcohol relapse. It also underscores the importance of adequate treatment of PTSD as reactivity related to trauma cues and reminders may be an important factor in craving and relapse. PMID- 27368086 TI - Phase separation of cesium from lead borosilicate glass by heat treatment under a reducing atmosphere. AB - A phase-separation technique for removing sodium from glass using a heat treatment method under a reducing atmosphere was previously developed for sodium recovery from waste glass. In this study, this technique was applied to cesium containing lead borosilicate glass to concentrate the cesium in phase-separated sodium-rich materials for efficient cesium extraction. The theoretical phase separation temperature of the sodium-rich phase was simulated by thermodynamic equilibrium calculations and was predicted to occur below 700 degrees C for lead borosilicate glass. Experimentally, a simulated lead borosilicate glass was melted at 1000 degrees C and subsequently annealed below 700 degrees C under a CO containing reducing atmosphere. The phase separation of cesium was found to occur with sodium enrichment on the glass surface that was in contact with the gas phase, promoting cesium extraction from the treated glass using water. The cesium extraction efficiency was affected by the surface area of the treated glass that was in contact with water, and under the examined conditions, the cesium extraction efficiency was up to 66%. Phase separation using reductive heat treatment, combined with a water leaching technique, is suggested to be effective for extracting cesium incorporated in borosilicate glass waste. PMID- 27368087 TI - Understanding the fate of polycyclic aromatic hydrocarbons at a forest fire site using a conceptual model based on field monitoring. AB - Forest fires are a well-known source of polycyclic aromatic hydrocarbons (PAHs). After forest fires, residual ash above a soil layer can be highly contaminated with PAHs. However, little is known about the fate of these contaminants, particularly about their susceptibility to be transferred deeper into underlying soil or downstream during rainfall events. In this study, meteorological conditions, organic carbon (OC) content, and the 16 US-EPA priority PAHs in unburnt control soil, burnt soil, and ash were monitored for 16 months after a forest fire. Whereas the ash was significantly contaminated with PAHs, the levels of PAHs in the underlying burnt soil were similar to those of the control soil. In the ash bed, the levels of PAHs normalized by OC also decreased. Neither PAHs nor OC lost from the ash bed was substantially transferred to the underlying soil. Instead, significant amounts of PAHs in the ash bed were likely removed by surface runoff. Light PAHs were dominantly emitted from the forest fire, but they showed higher decreasing rates with total precipitation. These findings were explained by a conceptual model for the fate of PAHs, involving four distinct processes related to precipitation and two states of the ash bed. PMID- 27368088 TI - Concordance and reproducibility of a next generation mtGenome sequencing method for high-quality samples using the Illumina MiSeq. AB - Sanger-type sequencing (STS) of mitochondrial DNA (mtDNA), specifically the control region (CR), is routinely employed in forensics in human identification and missing persons scenarios. Yet next-generation sequencing (NGS) has the potential to overcome some of the major limitations of STS processing, permitting reasonable paths forward for full mitochondrial genome (mtGenome) sequencing, while also offering higher-throughput and higher sensitivity capabilities. To establish the accuracy and reproducibility of NGS for the development of mtDNA data, 90 DNA extracts that were previously used to generate forensic quality full mtGenomes using STS were sequenced using Nextera XT library preparation and the Illumina MiSeq. Using the same amplicon product, replicate library sets were generated and sequenced at different laboratories, and analysis was performed in replicate using the CLC Genomics Workbench. Both sequencing sets resulted in 99.998% of positions with greater than 10X coverage when 96 samples (including controls) were multiplexed. Overall, 99.9996% concordance was observed between the NGS data and the STS data for the full mtGenome. The only "discordant" calls involved low level point heteroplasmies, with the differences resulting from stochastic variation and/or the increased sensitivity of NGS. Higher sensitivity also allowed for the detection of a mixed sample previously not detected with STS. Additionally, variant calls were reproducible between sequencing sets and between software analysis versions with the variant frequency only differing by 0.23% and 0.01%, respectively. Further validation studies and specialized software functionality tailored to forensic practice should facilitate the incorporation of NGS processing into standard casework applications. The data herein comprise the largest, and likely most thoroughly examined, complete mtGenome STS-NGS concordance dataset available. PMID- 27368089 TI - Analytical method development for powder characterization: Visualization of the critical drug loading affecting the processability of a formulation for direct compression. AB - Characterization of particulate systems (powders) is one of the remaining scientific challenges. Evaluation of powder behaviour is often empirical and the decision-making processes are experience-based. There is a need for development of analytical instrumentation enabling more fundamental understanding of powder behaviour. Flowability and tabletability, two key factors in commercial scale manufacturing of tablets with direct compression (DC) approach, were analysed for formulations containing increasing amounts of several model active pharmaceutical ingredients (APIs). Flowability was investigated using a ring shear tester and tablets were prepared at four different compression pressures using a single punch tablet press. Thereby, a material sparing screening approach was developed to estimate the influence of APIs on behaviour of a given DC formulation. Additionally, this approach is useful for estimating the low threshold amount of API (wt%), at which the properties of an API start affecting the powder behaviour of a given formulation (API-excipient mixture). This threshold will be referred to as critical drug loading. The flowability of microcrystalline cellulose (reference grade pH 102) was used as a threshold for adequate flowability of model formulations. The threshold for tablet tensile strength was set to 2MPa. Simultaneous visual presentation of both- flowability and tabletability were used for a fast evaluation of manufacturability of a given formulation. The results confirmed that flowability is more sensitive to drug loading than tabletability, and that the critical drug loading for a DC formulation is strongly affected by particulate properties of API. For example, decreasing the particle size of paracetamol led to rapid decrease in flowability index, whereas the tabletability was not affected. PMID- 27368090 TI - Examination of the Pattern of Growth of Cerebral Tissue Volumes From Hospital Discharge to Early Childhood in Very Preterm Infants. AB - IMPORTANCE: Smaller cerebral volumes at hospital discharge in very preterm (VPT) infants are associated with poor neurobehavioral outcomes. Brain growth from the newborn period to middle childhood has not been explored because longitudinal data have been lacking. OBJECTIVES: To examine the pattern of growth of cerebral tissue volumes from hospital discharge to childhood in VPT infants and to determine perinatal risk factors for impaired brain growth and associations with neurobehavioral outcomes at 7 years. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of VPT infants (<30 weeks' gestation or <1250 g) born between April 11, 2001, and April 26, 2004, and followed up at 7 years' corrected age. The setting was The Royal Women's Hospital and The Royal Children's Hospital, Melbourne, Australia. Of 224 VPT infants and 46 full-term (FT) infants, usable magnetic resonance imaging data at either infancy or 7 years were collected for 214 VPT children (95.5%) and 46 FT children (100%), while 126 VPT children (56.3%) and 31 FT children (67.4%) had usable magnetic resonance imaging data at both time points. Follow-up was conducted from April 28, 2008, to August 9, 2011. Our final analysis was on March 3, 2016. EXPOSURE: Prematurity. MAIN OUTCOMES AND MEASURES: Absolute tissue growth, defined as change in absolute tissue volume, between infancy and 7 years was calculated for cortical gray matter volume (GMV), white matter volume (WMV), and subcortical GMV. IQ, language, and motor function were measured at 7 years. RESULTS: The study cohort comprised 260 participants. Their mean (SD) age was 7.5 (0.2) years, and 49.2% (128 of 260) were female. Early GMV deficits in VPT infants were magnified by 7 years, with less growth than FT controls. Growth differences were 31.4 (95% CI, 14.8-48.1) cm3 for cortical GMV and 1.7 (95% CI, 0.5-2.8) cm3 for subcortical GMV. Within the VPT group, greater growth was observed in boys for cortical GMV (31.9; 95% CI, 16.8-46.9 cm3), WMV (31.7; 95% CI, 19.7-43.7 cm3), and subcortical GMV (1.8; 95% CI, 0.8-2.8 cm3). After controlling for sex and maternal education, all tissue volumes in infancy correlated with IQ (r >= 0.35, P < .05) and language (r >= 0.29, P < .05). Seven-year volumes correlated with IQ (r = 0.28, P = .04 for cortical GMV), language (r = 0.29, P = .04 for cortical GMV), and motor functioning (r >= 0.29, P < .05 for all tissues). There was no evidence of any association between brain growth during childhood and outcomes in VPT infants. CONCLUSIONS AND RELEVANCE: Low brain volumes observed in VPT infants are exaggerated at 7 years. Low brain volume in infancy is associated with long-term functional outcomes, emphasizing the persisting influence of early brain development on subsequent growth and outcomes. PMID- 27368091 TI - A Dengue Vaccine. AB - Denvaxia is the first licensed vaccine for the prevention of dengue. It is a live vaccine developed using recombinant DNA technology. The vaccine is given as three doses over the course of a year and has the potential to prevent hundreds of thousands of hospitalizations each year. PMID- 27368092 TI - Forging Collaborative Relationships in Brazil: From AIDS to ZIKV. AB - The Zika virus (ZIKV) outbreak has stimulated collaborations between Brazilians, researchers from other South American countries, and scientists from around the world. The Brazilian response to the HIV/AIDS epidemic demonstrates capabilities that can be applied to the study of ZIKV and provides lessons for developing effective international infectious disease research collaborations. PMID- 27368093 TI - Roots, Not Parachutes: Research Collaborations Combat Outbreaks. AB - Recent infectious disease epidemics illustrate how health systems failures anywhere can create disease vulnerabilities everywhere. We must therefore prioritize investments in health care infrastructure in outbreak-prone regions of the world. We describe how "rooted" research collaborations can establish capacity for pathogen surveillance and facilitate rapid outbreak responses. PMID- 27368094 TI - Mitochondrial Networking in T Cell Memory. AB - T-lymphocytes show large changes in ATP demand and nutrient utilization, imposed by their different roles as T memory and T effector cells. Therefore, T cell remodeling represents a bioenergetic challenge to mitochondria. New work from Buck et al. links changes in mitochondrial shape to T cell fate choice. PMID- 27368095 TI - Evidence of G.O.D.'s Miracle: Unearthing a RAG Transposon. AB - Diversity of antibodies and T cell receptors is generated by gene rearrangement dependent on RAG1 and RAG2, enzymes predicted to have been derived from a transposable element (TE) that invaded an immunoglobulin superfamily gene early in the evolution of jawed vertebrates. Now, Huang et al. report the discovery of ProtoRAG in the lower chordate Amphioxus, the long-anticipated TE related to the RAG transposon. PMID- 27368096 TI - Sorting Out Presenilins in Alzheimer's Disease. AB - Mutations in the presenilins that cause familial Alzheimer's disease alter the activity of these proteases to increase generation of an aggregation-prone isoform of the amyloid beta-peptide (Abeta). How these mutations do so has been unclear. Sannerud et al. now show that regulation of subcellular localization plays a central role, advancing our understanding of the cell biology of Alzheimer's disease. PMID- 27368097 TI - Actuators Acting without Actin. AB - Plant actuators move organs, allowing the plant to respond to environmental cues or perform other mechanical tasks. In Cardamine hursuta the dispersal of seeds is accomplished by explosive opening of the fruit. The biomechanical mechanism relies on a complex interplay between turgor regulation and cell wall mechanical properties. PMID- 27368098 TI - Neuronal Computations Made Visible with Subcellular Resolution. AB - Sensory information is gradually processed within dedicated neural circuits to generate specific behaviors. In this issue, Yang et al. push technology boundaries to measure both voltage and calcium signals from subcellular compartments of genetically defined interconnected neurons and shed light on local neural computations critical for motion detection. PMID- 27368099 TI - EMT: 2016. AB - The significant parallels between cell plasticity during embryonic development and carcinoma progression have helped us understand the importance of the epithelial-mesenchymal transition (EMT) in human disease. Our expanding knowledge of EMT has led to a clarification of the EMT program as a set of multiple and dynamic transitional states between the epithelial and mesenchymal phenotypes, as opposed to a process involving a single binary decision. EMT and its intermediate states have recently been identified as crucial drivers of organ fibrosis and tumor progression, although there is some need for caution when interpreting its contribution to metastatic colonization. Here, we discuss the current state-of the-art and latest findings regarding the concept of cellular plasticity and heterogeneity in EMT. We raise some of the questions pending and identify the challenges faced in this fast-moving field. PMID- 27368100 TI - Multi-organ Site Metastatic Reactivation Mediated by Non-canonical Discoidin Domain Receptor 1 Signaling. AB - Genetic screening identifies the atypical tetraspanin TM4SF1 as a strong mediator of metastatic reactivation of breast cancer. Intriguingly, TM4SF1 couples the collagen receptor tyrosine kinase DDR1 to the cortical adaptor syntenin 2 and, hence, to PKCalpha. The latter kinase phosphorylates and activates JAK2, leading to the activation of STAT3. This non-canonical mechanism of signaling induces the expression of SOX2 and NANOG; sustains the manifestation of cancer stem cell traits; and drives metastatic reactivation in the lung, bone, and brain. Bioinformatic analyses and pathological studies corroborate the clinical relevance of these findings. We conclude that non-canonical DDR1 signaling enables breast cancer cells to exploit the ubiquitous interstitial matrix component collagen I to undergo metastatic reactivation in multiple target organs. PMID- 27368101 TI - Paracrine Induction of HIF by Glutamate in Breast Cancer: EglN1 Senses Cysteine. AB - The HIF transcription factor promotes adaptation to hypoxia and stimulates the growth of certain cancers, including triple-negative breast cancer (TNBC). The HIFalpha subunit is usually prolyl-hydroxylated by EglN family members under normoxic conditions, causing its rapid degradation. We confirmed that TNBC cells secrete glutamate, which we found is both necessary and sufficient for the paracrine induction of HIF1alpha in such cells under normoxic conditions. Glutamate inhibits the xCT glutamate-cystine antiporter, leading to intracellular cysteine depletion. EglN1, the main HIFalpha prolyl-hydroxylase, undergoes oxidative self-inactivation in the absence of cysteine both in biochemical assays and in cells, resulting in HIF1alpha accumulation. Therefore, EglN1 senses both oxygen and cysteine. PMID- 27368103 TI - Irreversible APC(Cdh1) Inactivation Underlies the Point of No Return for Cell Cycle Entry. AB - Proliferating cells must cross a point of no return before they replicate their DNA and divide. This commitment decision plays a fundamental role in cancer and degenerative diseases and has been proposed to be mediated by phosphorylation of retinoblastoma (Rb) protein. Here, we show that inactivation of the anaphase promoting complex/cyclosome (APC(Cdh1)) has the necessary characteristics to be the point of no return for cell-cycle entry. Our study shows that APC(Cdh1) inactivation is a rapid, bistable switch initiated shortly before the start of DNA replication by cyclin E/Cdk2 and made irreversible by Emi1. Exposure to stress between Rb phosphorylation and APC(Cdh1) inactivation, but not after APC(Cdh1) inactivation, reverted cells to a mitogen-sensitive quiescent state, from which they can later re-enter the cell cycle. Thus, APC(Cdh1) inactivation is the commitment point when cells lose the ability to return to quiescence and decide to progress through the cell cycle. PMID- 27368102 TI - An ER-Associated Pathway Defines Endosomal Architecture for Controlled Cargo Transport. AB - Through a network of progressively maturing vesicles, the endosomal system connects the cell's interior with extracellular space. Intriguingly, this network exhibits a bilateral architecture, comprised of a relatively immobile perinuclear vesicle "cloud" and a highly dynamic peripheral contingent. How this spatiotemporal organization is achieved and what function(s) it curates is unclear. Here, we reveal the endoplasmic reticulum (ER)-located ubiquitin ligase Ring finger protein 26 (RNF26) as the global architect of the entire endosomal system, including the trans-Golgi network (TGN). To specify perinuclear vesicle coordinates, catalytically competent RNF26 recruits and ubiquitinates the scaffold p62/sequestosome 1 (p62/SQSTM1), in turn attracting ubiquitin-binding domains (UBDs) of various vesicle adaptors. Consequently, RNF26 restrains fast transport of diverse vesicles through a common molecular mechanism operating at the ER membrane, until the deubiquitinating enzyme USP15 opposes RNF26 activity to allow vesicle release into the cell's periphery. By drawing the endosomal system's architecture, RNF26 orchestrates endosomal maturation and trafficking of cargoes, including signaling receptors, in space and time. PMID- 27368104 TI - Information Integration and Energy Expenditure in Gene Regulation. AB - The quantitative concepts used to reason about gene regulation largely derive from bacterial studies. We show that this bacterial paradigm cannot explain the sharp expression of a canonical developmental gene in response to a regulating transcription factor (TF). In the absence of energy expenditure, with regulatory DNA at thermodynamic equilibrium, information integration across multiple TF binding sites can generate the required sharpness, but with strong constraints on the resultant "higher-order cooperativities." Even with such integration, there is a "Hopfield barrier" to sharpness; for n TF binding sites, this barrier is represented by the Hill function with the Hill coefficient n. If, however, energy is expended to maintain regulatory DNA away from thermodynamic equilibrium, as in kinetic proofreading, this barrier can be breached and greater sharpness achieved. Our approach is grounded in fundamental physics, leads to testable experimental predictions, and suggests how a quantitative paradigm for eukaryotic gene regulation can be formulated. PMID- 27368105 TI - SnapShot: Brown and Beige Adipose Thermogenesis. AB - Brown and beige adipose tissues have been identified as potential therapeutic targets for combating diet-induced obesity and metabolic disease. Here, we present transcriptional and developmental regulation of brown and beige adipose tissue, as well as critical physiological and pharmaceutical activators of thermogenesis in both tissues. PMID- 27368107 TI - Is the clinical use of ice still relevant? PMID- 27368106 TI - Risk factors for level V lymph node metastases in solitary papillary thyroid carcinoma with clinically lateral lymph node metastases. AB - The extent of lateral neck dissection (LND) in surgical resection of papillary thyroid carcinoma (PTC) with clinically lateral LNM (LLNM) remains controversial. We aimed to explore the frequency of and risk factors for level V LNM in patients with solitary PTC and clinically LLNM. To analyze the frequency and risk factors for level V LNM, we retrospectively reviewed 220 solitary PTC patients who underwent total thyroidectomy, bilateral central neck dissection, and therapeutic LND. LLNM were present in 82.3% patients, and levels II-V LNM were present in 45.9%, 62.7%, 55.5%, and 12.3% patients, respectively. Ipsilateral level V LNM was significantly associated with tumor size >10 mm, extrathyroidal extension, ipsilateral central LNM ratio >=50%, and contralateral central LNM (CLNM), bilateral CLNM, and simultaneous levels II-IV LNM. Contralateral CLNM was an independent risk factor for level V LNM. In patients with solitary PTC and clinically LLNM, level V LNM was relatively uncommon. Therefore, routine level V lymphadenectomy may be unnecessary in these patients unless level V LNM is suspected on preoperative examination or associated risk factors, especially contralateral CLNM, are present. PMID- 27368108 TI - Aspiring to inspire - serotonin, the laryngeal chemoreflex and the sudden infant death syndrome. PMID- 27368109 TI - TPGS-modified liposomes for the delivery of ginsenoside compound K against non small cell lung cancer: formulation design and its evaluation in vitro and in vivo. AB - OBJECTIVE: This work aimed at preparing ginsenoside compound K (GCK)-loaded liposomes modified with TPGS (GCKT-liposomes) to enhance solubility and targeting capability of GCK, as well as inhibit the efflux of GCK from tumour cells. METHODS: GCKT-liposomes were prepared by the thin-film hydration method and characterized by particle size, polydispersity, zeta potential and drug encapsulation efficiency. A549 cells were used as antitumour cell model to access the cellular uptake of the GCK and perform its antitumour function. The enhancement of in vivo antitumour efficacy of GCKT-liposomes was evaluated by nude mice bearing tumour model. KEY FINDINGS: The results showed that GCKT liposomes achieved a comparatively high drug loading efficiency and reasonable particle size at the ratio of 7 : 3 (phospholipid: TPGS). The in vitro release demonstrated that the dissolution of GCK was remarkably improved by entrapping it into liposomes. In addition, GCKT-liposomes exhibited a great hypersensitizing effect on A549 cells, and the cellular uptake was enhanced. Compared with free GCK, the IC50 of GCKT-liposomes was significantly reduced (16.3 +/- 0.8 vs 24.9 +/- 1.0 MUg/ml). In vivo antitumour assay also indicated that GCKT-liposomes achieved higher antitumour efficacy (67.5 +/- 0.5 vs 40.8 +/- 0.7%). CONCLUSION: The novel GCKT-liposomes significantly improved the antitumour efficacy of GCK. PMID- 27368110 TI - Association Between Trauma Center Type and Mortality Among Injured Adolescent Patients. AB - IMPORTANCE: Although data obtained from regional trauma systems demonstrate improved outcomes for children treated at pediatric trauma centers (PTCs) compared with those treated at adult trauma centers (ATCs), differences in mortality have not been consistently observed for adolescents. Because trauma is the leading cause of death and acquired disability among adolescents, it is important to better define differences in outcomes among injured adolescents by using national data. OBJECTIVES: To use a national data set to compare mortality of injured adolescents treated at ATCs, PTCs, or mixed trauma centers (MTCs) that treat both pediatric and adult trauma patients and to determine the final discharge disposition of survivors at different center types. DESIGN, SETTING, AND PARTICIPANTS: Data from level I and II trauma centers participating in the 2010 National Trauma Data Bank (January 1 to December 31, 2010) were used to create multilevel models accounting for center-specific effects to evaluate the association of center characteristics (PTC, ATC, or MTC) on mortality among patients aged 15 to 19 years who were treated for a blunt or penetrating injury. The models controlled for sex; mechanism of injury (blunt vs penetrating); injuries sustained, based on the Abbreviated Injury Scale scores (post-dot values <3 or >=3 by body region); initial systolic blood pressure; and Glasgow Coma Scale scores. Missing data were managed using multiple imputation, accounting for multilevel data structure. Data analysis was conducted from January 15, 2013, to March 15, 2016. EXPOSURES: Type of trauma center. MAIN OUTCOMES AND MEASURES: Mortality at each center type. RESULTS: Among 29 613 injured adolescents (mean [SD] age, 17.3 [1.4] years; 72.7% male), most were treated at ATCs (20 402 [68.9%]), with the remainder at MTCs (7572 [25.6%]) or PTCs (1639 [5.5%]). Adolescents treated at PTCs were more likely to be injured by a blunt than penetrating injury mechanism (91.4%) compared with those treated at ATCs (80.4%) or MTCs (84.6%). Mortality was higher among adolescents treated at ATCs and MTCs than those treated at PTCs (3.2% and 3.5% vs 0.4%; P < .001). The adjusted odds of mortality were higher at ATCs (odds ratio, 4.19; 95% CI, 1.30-13.51) and MTCs (odds ratio, 6.68; 95% CI, 2.03-21.99) compared with PTCs but was not different between level I and II centers (odds ratio, 0.76; 95% CI, 0.59-0.99). CONCLUSION AND RELEVANCE: Mortality among injured adolescents was lower among those treated at PTCs, compared with those treated at ATCs and MTCs. Defining resource and patient features that account for these observed differences is needed to optimize adolescent outcomes after injury. PMID- 27368111 TI - Rapid determination of nine barbiturates in human whole blood by liquid chromatography-tandem mass spectrometry. AB - A rapid, simple and sensitive liquid chromatography-tandem mass spectrometry (LC MS/MS) method was developed for the qualitative and quantitative analysis of nine barbiturates (barbital, phenobarbital, pentobarbital, amobarbital, secobarbital, thiopental, butalbital, butabarbital, and hexobarbital) in human whole blood. Barbiturates were extracted from 100 MUL of human whole blood samples using a simple liquid-liquid extraction (LLE) procedure, and detected by LC-MS/MS. An UPLC C18 (2.1 mm * 100 mm, 1.7 um) column was used at 40 degrees C for the separation and acetonitrile/water system was used as the mobile phase with gradient elution. This method showed excellent accuracy (86-111%) and precision (relative standard deviation <15%). The limits of detection (LODs) were 0.2 ng/mL for barbital and secobarbital and 0.5 ng/mL for the other barbiturates. The linearity ranged from 2 ng/mL to 2000 ng/mL, with r2 > 0.99 over the range. This method achieved the separation and detection of pentobarbital and amobarbital at the same time in a convenient way. Moreover, it was both simple and sensitive for the determination of nine most commonly used barbiturate drugs, which was meaningful in the field of clinical and forensic toxicology. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27368112 TI - Midwest Nursing Research Society News. PMID- 27368113 TI - Hb Melusine and Hb Athens-Georgia: potentially underreported in the Belgian population? Four cases demonstrating the lack of detection using common CE-HPLC methods either for glycated hemoglobin (HbA1C) analysis or Hb variant screening. AB - OBJECTIVE AND IMPORTANCE: Suspected hemoglobin (Hb) variants, detected during HbA1C measurements should be further investigated, determining the extent of the interference with each method. CLINICAL PRESENTATION: This is the first report of Hb Melusine and Hb Athens-Georgia in Caucasian Belgian patients. Intervention & Technique: Since common CE-HPLC methods for HbA1C analysis or Hb variant screening are apparently unable to detect these Hb variants, their presence might be underestimated. HbA1C analysis using CZE, however, alerted for their presence. Moreover, in case of Hb Melusine, even Hb variant screening using CZE was unsuccessful in its detection. CONCLUSION: Fortunately, carriage of Hb Melusine or Hb Athens-Georgia variants has no clinical implications and, as shown in this report, no apparent difference in HbA1C should be expected. PMID- 27368114 TI - DNA Damage Repair and the Emerging Role of Poly(ADP-ribose) Polymerase Inhibition in Cancer Therapeutics. AB - PURPOSE: As a result of improved understanding of DNA repair mechanisms, poly(ADP ribose) polymerase inhibitors (PARPi) are increasingly recognized to play an important therapeutic role in the treatment of cancer. The aim of this article is to provide a review of PARPi function in DNA damage repair and synthetic lethality and to demonstrate how these mechanisms can be exploited to provide new PARPi-based therapies to patients with solid tumors. METHODS: Literature from a range of sources, including PubMed and MEDLINE, were searched to identify recent reports regarding DNA damage repair and PARPi. FINDINGS: DNA damage repair is central to cellular viability. The family of poly(ADP-ribose) polymerase proteins play multiple intracellular roles in DNA repair, but function primarily in the resolution of repair of single-strand DNA breaks. Insights through the discovery of germline BRCA1/2 mutations led to the understanding of synthetic lethality and the potential therapeutic role of PARPi in the treatment of cancer. Further understanding of DNA damage repair and the concept of BRCA-like tumors have catalyzed PARPi clinical investigation in multiple oncologic settings. IMPLICATIONS: PARPi hold great promise in the treatment of solid tumors, both as monotherapy and in combination with other cancer therapeutics. Multiple PARPi clinical trials are currently underway. Further understanding of aberrant DNA repair mechanisms in the germline and in the tumor genome will allow clinicians and researchers to apply PARPi most strategically in the era of personalized medicine. PMID- 27368115 TI - Concordant and Discordant EGFR Mutations in Patients With Multifocal Adenocarcinomas: Implications for EGFR-Targeted Therapy. AB - PURPOSE: Adenocarcinoma remains the most common subtype of lung cancer in the United States. Most patients present with tumors that are invasive and often metastatic, but in some patients, multiple precursor in situ or minimally invasive adenocarcinoma tumors develop that can be synchronous and metachronous. These precursor lesions harbor the same spectrum of genetic mutations found in purely invasive adenocarcinomas, such as EGFR, KRAS, and p53 mutations. It is less clear, however, whether separate lesions in patients who present with multifocal disease share common underlying genetic driver mutations. METHODS: Here we review the relevant literature on molecular driver alterations in adenocarcinoma precursor lesions. We then report 4 patients with multifocal EGFR mutant adenocarcinomas in whom we performed molecular testing on 2 separate lesions. FINDINGS: In 2 of these patients, the mutations are concordant, and in 2 patients, the mutations are discordant. A review of the literature demonstrates increasing evidence that lesions with discordant mutations may confer a more favorable prognosis because they are unlikely to represent metastases. IMPLICATIONS: Our findings suggest that the emergence of the dominant EGFR driver alteration is often independent between lesions in patients with multifocal adenocarcinomas, and thus the same targeted therapy may not be effective for all lesions. However, genetic testing of multiple lesions can help to distinguish separate primary tumors from metastatic disease. PMID- 27368117 TI - A Randomized Phase I Pharmacokinetic Study Comparing Biosimilar Candidate SB3 and Trastuzumab in Healthy Male Subjects. AB - PURPOSE: This first-in-human study with SB3 was designed to evaluate the pharmacokinetic (PK) equivalence between SB3 and trastuzumab sourced in the European Union (EU trastuzumab), between SB3 and trastuzumab sourced in the United States (US trastuzumab), and between EU and US trastuzumab (NCT02075073). METHODS: In this randomized, double-blind, parallel group, single-dose comparative PK study, 109 healthy male subjects were randomized to receive a single 6-mg/kg IV dose of SB3, EU -trastuzumab, or US trastuzumab. The PK parameters were calculated using noncompartmental methods. The PK equivalence in terms of AUC0--infinity), AUC0-last, and Cmax for the pairwise comparisons (SB3 vs EU trastuzumab, SB3 vs US trastuzumab, and EU trastuzumab vs US trastuzumab) were determined using the predefined equivalence margin of 0.8 to 1.25. FINDINGS: Baseline demographic characteristics for the randomized subjects were similar across the 3 groups. The 90% CIs for the geometric least square means of the AUC0 infinity, AUC0-last, and Cmax were completely contained within the margin of 0.8 to 1.25. The proportions of subjects who experienced adverse events related to the study drug were 36.1%, 44.4%, and 61.1% in the SB3, EU trastuzumab, and US trastuzumab groups, respectively. The most frequently reported adverse events related to the study drug was infusion-related reactions. No subjects had positive results for antidrug antibodies after a single dose of SB3, EU trastuzumab, or US trastuzumab. IMPLICATIONS: This study revealed PK equivalence between SB3 and EU trastuzumab, between SB3 and US trastuzumab, and between EU trastuzumab and US trastuzumab. SB3 is well tolerated without tolerability concerns after single-dose administration in healthy male subjects. PMID- 27368116 TI - A Prospective Evaluation of the Effects of Prevalent Depressive Symptoms on Disease Activity in Rheumatoid Arthritis Patients Treated With Biologic Response Modifiers. AB - PURPOSE: Depressive symptoms are common in rheumatoid arthritis (RA) and may affect disease activity and treatment outcomes. The objective of this study was to determine if prevalent depressive symptoms modify biologic treatment response through their effect on RA disease activity. METHODS: RA patients with depressive symptoms, initiating biologic treatment, were identified from a US RA registry sample. Patients with depression were compared with control subjects (ie, those patients with no reports of depressive symptoms at, or before, initiating therapy) in terms of clinical disease activity index (CDAI) remission and low disease activity (LDA), and the changes in the component measures that comprise this scale at 6 and 12 months of follow-up. Inverse probability weighting was used to account for differences in baseline disease severity, concomitant treatment characteristics, and other possible confounders. Logistic and linear regression models estimated differences in response rates and changes in component disease activity measures. FINDINGS: Depressive symptoms were associated with a decreased likelihood of CDAI remission at 6 months (odds ratio, 0.43 [95% CI, 0.19-0.96]) but not at 12 months (odds ratio, 0.83 [95% CI, 0.43 1.60]), and there was no effect on CDAI LDA. Adjusted core component measurement changes showed smaller decreases in global assessment ratings in patients with depressive symptoms; these associations were not statistically significant. IMPLICATIONS: Poorer treatment outcomes among RA patients with depressive symptoms may be a result of higher baseline disease severity. Adjusted estimates indicated symptoms of depression only affected remission at 6 months' follow-up through patient and physician global assessments. Thus, any impact of depressive symptoms during biologic treatment might not be due to a definitive impact on joint swelling and tenderness. PMID- 27368118 TI - Relationship Between Time Consumption and Quality of Responses to Drug-related Queries: A Study From Seven Drug Information Centers in Scandinavia. AB - PURPOSE: The aims of this study were to assess the quality of responses produced by drug information centers (DICs) in Scandinavia, and to study the association between time consumption processing queries and the quality of the responses. METHODS: We posed six identical drug-related queries to seven DICs in Scandinavia, and the time consumption required for processing them was estimated. Clinical pharmacologists (internal experts) and general practitioners (external experts) reviewed responses individually. We used mixed model linear regression analyses to study the associations between time consumption on one hand and the summarized quality scores and the overall impression of the responses on the other hand. FINDINGS: Both expert groups generally assessed the quality of the responses as "satisfactory" to "good." A few responses were criticized for being poorly synthesized and less relevant, of which none were quality-assured using co signatures. For external experts, an increase in time consumption was statistically significantly associated with a decrease in common quality score (change in score, -0.20 per hour of work; 95% CI, -0.33 to -0.06; P = 0.004), and overall impression (change in score, -0.05 per hour of work; 95% CI, -0.08 to 0.01; P = 0.005). No such associations were found for the internal experts' assessment. IMPLICATIONS: To our knowledge, this is the first study of the association between time consumption and quality of responses to drug-related queries in DICs. The quality of responses were in general good, but time consumption and quality were only weakly associated in this setting. PMID- 27368119 TI - The parathyroid hormone-related protein is secreted during the osteogenic differentiation of human dental follicle cells and inhibits the alkaline phosphatase activity and the expression of DLX3. AB - The dental follicle is involved in tooth eruption and it expresses a great amount of the parathyroid hormone-related protein (PTHrP). PTHrP as an extracellular protein is required for a multitude of different regulations of enchondral bone development and differentiation of bone precursor cells and of the development of craniofacial tissues. The dental follicle contains also precursor cells (DFCs) of the periodontium. Isolated DFCs differentiate into periodontal ligament cells, alveolar osteoblast and cementoblasts. However, the role of PTHrP during the human periodontal development remains elusive. Our study evaluated the influence of PTHrP on the osteogenic differentiation of DFCs under in vitro conditions for the first time. The PTHrP protein was highly secreted after 4days of the induction of the osteogenic differentiation of DFCs with dexamethasone (2160.5pg/ml+/-345.7SD. in osteogenic differentiation medium vs. 315.7pg/ml+/ 156.2SD. in standard cell culture medium; Student's t Test: p<0.05 (n=3)). We showed that the supplementation of the osteogenic differentiation medium with PTHrP inhibited the alkaline phosphatase activity and the expression of the transcription factor DLX3, but the depletion of PTHrP did not support the differentiation of DFCs. Previous studies have shown that Indian Hedgehog (IHH) induces PTHrP and that PTHrP, in turn, inhibits IHH via a negative feedback loop. We showed that SUFU (Suppressor Of Fused Homolog) was not regulated during the osteogenic differentiation in DFCs. So, neither the hedgehog signaling pathway induced PTHrP nor PTHrP suppressed the hedgehog signaling pathway during the osteogenic differentiation in DFCs. In conclusion, our results suggest that PTHrP regulates independently of the hedgehog signaling pathway the osteogenic differentiated in DFCs. PMID- 27368120 TI - A Micro-Polyethylene Glycol Precipitation Assay as a Relative Solubility Screening Tool for Monoclonal Antibody Design and Formulation Development. AB - Adequate protein solubility is an important prerequisite for development, manufacture, and administration of biotherapeutic drug candidates, especially for high-concentration protein formulations. A previously established method for determining the relative apparent solubility (thermodynamic activity) of proteins using polyethylene glycol (PEG) precipitation is adapted for screening and comparing monoclonal antibody (mAb) candidates where only limited quantities (<=1 mg) are available. This micro-PEG assay is used to evaluate various broadly neutralizing mAb candidates to HIV-1 viral spike (gp120 and gp41 glycoproteins). Using ~1 mg of VRC01-WT mAb per assay, the precision of the micro-PEG assay was established. A series of 7 different broadly neutralizing mAbs to the HIV-1 viral spike proteins were compared by curve shape (%PEG vs. protein concentration), %PEGmidpoint determinations, and extrapolated apparent solubility values. Numerous formulation conditions were then evaluated for their relative effects on the VRC01-WT mAb. The PEGmidpt and apparent solubility values of VRC01-WT mAb decreased as the solution pH increased and increased as NaCl and arginine were added. A final optimization of the micro-PEG assay established that amounts as low as 0.1-0.2 mg can be used. Thus, the micro-PEG assay has significant potential as a relative solubility screening tool during candidate selection and early formulation development. PMID- 27368121 TI - Controlled Expansion of Supercritical Solution: A Robust Method to Produce Pure Drug Nanoparticles With Narrow Size-Distribution. AB - We introduce a robust, stable, and reproducible method to produce nanoparticles based on expansion of supercritical solutions using carbon dioxide as a solvent. The method, controlled expansion of supercritical solution (CESS), uses controlled mass transfer, flow, pressure reduction, and particle collection in dry ice. CESS offers control over the crystallization process as the pressure in the system is reduced according to a specific profile. Particle formation takes place before the exit nozzle, and condensation is the main mechanism for postnucleation particle growth. A 2-step gradient pressure reduction is used to prevent Mach disk formation and particle growth by coagulation. Controlled particle growth keeps the production process stable. With CESS, we produced piroxicam nanoparticles, 60 mg/h, featuring narrow size distribution (176 +/- 53 nm). PMID- 27368122 TI - Support Tools in Formulation Development for Poorly Soluble Drugs. AB - The need for solubility enhancement through formulation is a well-known but still problematic issue because of the numbers of poorly water-soluble drugs in development. There are several possible routes that can be taken to increase the bioavailability of drugs intended for immediate-release oral formulation. The best formulation strategy for any given drug will depend on numerous factors, including required dose, shelf life, manufacturability, and the properties of the active pharmaceutical ingredient (API). Choosing an optimal formulation and manufacturing route for a new API is therefore not a straightforward process. Currently, there are several approaches that are used in the pharmaceutical industry to select the best formulation strategy. These differ in complexity and efficiency, but most try to predict which route will best suit the API based on selected molecular parameters such as molecular weight, lipophilicity (logP), and solubility. These methods range from using no tools, trial and error methods through a variety of complex tools from small in vitro or in vivo experiments or high throughput screening, guidance maps, and decision trees to the most complex methods based on computational modelling tools. This review aims to list available support tools and explain how they are used. PMID- 27368124 TI - Muscle strength differ between patients with diabetes and controls following heart surgery. AB - BACKGROUND: The aim of our study was to analyze muscle strength in patients with recent surgical treatment for ischemic and combined ischemic-valvular heart disease, based on existence of diabetes mellitus. Connections existing between muscle strength and patient characteristics or conventional diagnostic tests were analyzed as well. METHODS: Study prospectively included consecutive patients scheduled for cardiovascular rehabilitation 0-3months after heart surgery. Diagnostics covered drug utilization, anthropometrics, demographics, echocardiography, conventional laboratory, echocardiography, bioelectrical impedance analysis (BIA), and hand grip test (HGT). HGT was analyzed for dominant hand. RESULTS: Patients with diabetes had significantly weaker muscle strength on HGT than controls; 29.4+/-12.2kg vs. 38.2+/-14.7kg (p=0.029), respectively. ROC analysis for HGT and existence of diabetes mellitus were significant; <=40kg had sensitivity of 89.7% (95%CI: 72.6-97.8), specificity 43.7% (31.9-56.0); AUC 0.669 (0.568-0.760); p=0.002. HGT significantly correlated with hematocrit (Rho CC=0.247; p=0.013), whilst other laboratory or echocardiographic parameters were insignificant (all p>0.05). HGT also correlated with body weight (Rho CC=0.510; p<0.001); height (Rho CC=0.632; p<0.001); waist circumference (Rho CC=0.388; p<0.001); waist-to-hip ratio (Rho CC=0.274; p=0.006) and BIA (Rho CC=-0.412; p<0.001). CONCLUSIONS: In postoperative recovery of patients with diabetes, muscle strength assessed by HGT is decreased and in relation with nutritional status. Clinically resourceful connections of HGT were also found to hematocrit and utilization of loop diuretics. PMID- 27368123 TI - Adiponectin is associated with early diabetic kidney disease in adults with type 1 diabetes: A Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study. AB - OBJECTIVE: The associations between elevated adiponectin and end-stage renal disease are well recognized and thought to be at least partially explained by reduced renal clearance. Conversely, the relationship between adiponectin and early diabetic kidney disease (DKD) with preserved glomerular filtration rate (GFR), including rapid GFR decline and incident chronic kidney disease (CKD) is unclear. We hypothesized that elevated adiponectin would be associated with early DKD in adults with type 1 diabetes. METHODS: Adults with type 1 diabetes (n=646 at baseline, n=525 at 6years) had adiponectin and renal function by estimated GFR (eGFR) by CKD-EPI creatinine and albumin-excretion rate (AER) evaluated at baseline and 6years. Linear and logistic models evaluated the associations of baseline adiponectin with AER, macroalbuminuria (AER >=200MUg/min), eGFR, CKD (<60mL/min/1.73m2) and rapid GFR decline (>3mL/min/1.73m2/year). Models adjusted for age, sex, duration, HbA1c, SBP, LDL-C and current smoking. RESULTS: Compared to non-diabetics, adults with type 1 diabetes had significantly higher adiponectin, and the difference remained significant after adjusting for AER and/or eGFR (p<0.0001). Adiponectin at baseline was positively associated with rapid GFR decline (OR: 1.24, 95% CI 1.00-1.53), incident CKD (OR: 1.75, 1.14 2.70), and persistent macroalbuminuria and CKD (OR: 1.61, 1.10-2.36) over 6years in adjusted models. The associations also remained significant after further adjustments for CRP, estimated insulin sensitivity and ACEi/ARB therapy. CONCLUSIONS: Adults with type 1 diabetes have higher adiponectin than their non diabetic peers, and elevated adiponectin at baseline is independently associated with greater odds of developing early DKD over 6years. PMID- 27368125 TI - p62 modulates the intrinsic signaling of UVB-induced apoptosis. AB - BACKGROUND: UVB radiation is the main source of sunburn and skin cancers. Apoptosis eliminates photodamaged cells, and is thus important for preventing epidermal carcinogenesis. The cytoplasmic regulatory protein p62/A170/sequestosome 1 (p62) molecule is involved in a variety of cellular and signaling pathways. p62 is known to be and important in autophagy, but its role in UVB-induced apoptosis remains to be clarified. OBJECTIVE: To investigate the role of p62 against UVB-induced apoptotic changes, using mouse embryonic fibroblasts (MEFs) derived from p62 homozygous knockout (p62(-/-)) mice. METHODS: p62(-/-) and wild-type (p62(+/+)) mice and MEFs were subjected to UVB irradiation, and the resultant apoptosis was analyzed using flow cytometry, quantitative real-time PCR, and western blots. RESULTS: Apoptosis was decreased in the p62(-/-) MEFs compared to p62(+/+) MEFs in response to UVB treatment. Compared with p62(+/+) MEFs, p62(-/-) MEFs expressed significantly more Bcl-2 and less Bax, and showed increased Src and Stat3 phosphorylation. Our results show that p62 regulates apoptotic pathways by modifying critical signaling intermediates such as Src and Stat3. CONCLUSION: p62 reduces UVB-induced apoptosis by modulating intrinsic apoptotic signaling through Src phosphorylation. PMID- 27368126 TI - Racial and Ethnic Disparities in Unmet Need for Pediatric Therapy Services: The Role of Family-Centered Care. AB - OBJECTIVE: To examine whether individual elements of family-centered care (FCC) mediate racial/ethnic disparities in parent-reported unmet therapy need. METHODS: We conducted a secondary data analysis using the 2009-2010 National Survey of Children With Special Health Care Needs. A total of 6478 black, Hispanic, and white children ages 0 to 5 years had complete data on parent-reported unmet need and FCC. Five measured indicators of FCC included whether the child's health care provider spent enough time with the child (time), listened carefully to the child's parents (listening), was sensitive to family culture and values (sensitivity), delivered information specific to the child's health (information), and helped parents feel like partners (partnership). We performed staged multivariate logistic regression to test the association between race/ethnicity and parent-reported unmet therapy need, and to explore whether this association was mediated by elements of FCC using the Baron-Kenny mediation framework. RESULTS: Eighteen percent of children with special health care needs 0 to 5 years old with reported therapy need experienced unmet need. Black and Hispanic children were more likely than white children to have parent-reported unmet therapy need (adjusted odds ratio 1.59, 95% confidence interval 1.08-2.36). This disparity was no longer significant after adjustment for the FCC elements of time, sensitivity, or partnership. CONCLUSIONS: The provision of FCC is likely an important factor in meeting the therapy needs of children with developmental delay and in reducing racial/ethnic disparities in parent-reported unmet therapy need. Interventions aimed at fostering parent-provider relationships through improved cultural sensitivity and engagement of parents as partners are necessary to ensure equitable utilization of these services. PMID- 27368127 TI - New hardware and workflows for semi-automated correlative cryo-fluorescence and cryo-electron microscopy/tomography. AB - Correlative light and electron microscopy allows features of interest defined by fluorescence signals to be located in an electron micrograph of the same sample. Rare dynamic events or specific objects can be identified, targeted and imaged by electron microscopy or tomography. To combine it with structural studies using cryo-electron microscopy or tomography, fluorescence microscopy must be performed while maintaining the specimen vitrified at liquid-nitrogen temperatures and in a dry environment during imaging and transfer. Here we present instrumentation, software and an experimental workflow that improves the ease of use, throughput and performance of correlated cryo-fluorescence and cryo-electron microscopy. The new cryo-stage incorporates a specially modified high-numerical aperture objective lens and provides a stable and clean imaging environment. It is combined with a transfer shuttle for contamination-free loading of the specimen. Optimized microscope control software allows automated acquisition of the entire specimen area by cryo-fluorescence microscopy. The software also facilitates direct transfer of the fluorescence image and associated coordinates to the cryo electron microscope for subsequent fluorescence-guided automated imaging. Here we describe these technological developments and present a detailed workflow, which we applied for automated cryo-electron microscopy and tomography of various specimens. PMID- 27368128 TI - Membrane protein crystallization in micelles conjugated by nucleoside base pairing: A different concept. AB - The dearth of high quality, three dimensional crystals of membrane proteins, suitable for X-ray diffraction analysis, constitutes a serious barrier to progress in structural biology. To address this challenge, we have developed a new crystallization medium that relies on the conjugation of surfactant micelles via base-pairing of complementary hydrophobic nucleosides. Base-pairs formed at the interface between micelles bring them into proximity with each other; and when the conjugated micelles contain a membrane protein, crystal nucleation centers can be stabilized, thereby promoting crystal growth. Accordingly, two hydrophobic nucleoside derivatives - deoxyguanosine (G) and deoxycytidine (C), each covalently bonded to a 10 carbon chain were synthesized and added to an aqueous solution containing octyl beta-d-thioglucopyranoside micelles. These hydrophobic nucleosides induced the formation of oil-rich globules after 2days incubation at 19 degrees C or after a few hours in the presence of ammonium sulfate; however, phase separation was inhibited by 100mM GMP. The presence of the membrane protein bacteriorhodopsin in the conjugated - micellar dispersion resulted in the growth within the colorless globules of a variety of purple crystals, the color indicating a functional protein. On this basis, we suggest that conjugation of micelles via base-pair complementarity may provide significant assistance to the structural determination of integral membrane proteins. PMID- 27368129 TI - Probing the mechanical properties, conformational changes, and interactions of nucleic acids with magnetic tweezers. AB - Nucleic acids are central to the storage and transmission of genetic information. Mechanical properties, along with their sequence, both enable and fundamentally constrain the biological functions of DNA and RNA. For small deformations from the equilibrium conformations, nucleic acids are well described by an isotropic elastic rod model. However, external forces and torsional strains can induce conformational changes, giving rise to a complex force-torque phase diagram. This review focuses on magnetic tweezers as a powerful tool to precisely determine both the elastic parameters and conformational transitions of nucleic acids under external forces and torques at the single-molecule level. We review several variations of magnetic tweezers, in particular conventional magnetic tweezers, freely orbiting magnetic tweezers and magnetic torque tweezers, and discuss their characteristic capabilities. We then describe the elastic rod model for DNA and RNA and discuss conformational changes induced by mechanical stress. The focus lies on the responses to torque and twist, which are crucial in the mechanics and interactions of nucleic acids and can directly be measured using magnetic tweezers. We conclude by highlighting several recent studies of nucleic acid protein and nucleic acid-small-molecule interactions as further applications of magnetic tweezers and give an outlook of some exciting developments to come. PMID- 27368130 TI - Comprehensive Biomarkers for Personalized Treatment in Pulmonary Large Cell Neuroendocrine Carcinoma: A Comparative Analysis With Adenocarcinoma. AB - BACKGROUND: The prognosis for patients with large cell neuroendocrine carcinoma (LCNEC) of the lung is extremely poor, and optimal treatment strategies have not yet been established. To improve prognoses in patients with LCNEC, this study analyzed immunohistochemical expression and gene mutations of several known molecular targets in LCNECs and compared the expression levels of these targets with those in lung adenocarcinomas. METHODS: Twenty-six patients with primary LCNEC and 40 patients with adenocarcinoma were analyzed. Excision repair cross complementation group 1 (ERCC1), class III beta-tubulin, topoisomerase I, topoisomerase II, epidermal growth factor receptor (EGFR)-L858R, and somatostatin receptor expression were evaluated by immunohistochemistry, and EGFR mutations were evaluated using direct DNA sequencing and the Scorpion-amplified refractory mutation system. RESULTS: In patients with LCNEC and adenocarcinoma, positive rates of topoisomerase I, topoisomerase II, ERCC1, class III beta-tubulin, EGFR L858R, and somatostatin were 100.0% and 100.0%, 65.4% and 15.0% (p < 0.0001), 42.3% and 17.5% (p = 0.0462), 46.2% and 62.5%, 0.0% and 20.0% (p = 0.0182), and 50.0% and 5.0% (p < 0.0001), respectively. The frequencies of EGFR mutations were 0.0% and 37.5% in LCNEC and adenocarcinoma (p = 0.0002), respectively. Five-year overall survival rates were 64% in LCNEC and 91% in adenocarcinoma in stage I (p = 0.0132). Multivariate analysis showed that LCNEC histologic type was an independent prognostic factor in stage I. CONCLUSIONS: LCNEC showed overexpression of topoisomerase II, somatostatin, and ERCC1. These findings suggested that it was possible to have good response to treatment with etoposide and octreotide and that LCNEC may be resistant to platinum-based therapy compared with adenocarcinoma. EGFR mutations were not observed in LCNEC. These results may indicate a favorable response to adjuvant treatments that are not typically prescribed for non-small cell lung cancer. PMID- 27368131 TI - Modest amendment of sewage sludge biochar to reduce the accumulation of cadmium into rice(Oryza sativa L.): A field study. AB - Much research has considered the influence of biochars on the availability and phytoaccumulation of potentially toxic elements (PTEs) from soil. However, the vast majority of these studies use, what are arguably, unrealistic and unpractical amounts of biochar (10, 50 and even up to 100 t/ha). To offer a more realistic insight into the influence of biochar on PTE partitioning and phytoaccumulation, a field study, using modest rates of biochar application (1.5, 3.0 t/ha), was undertaken. Specifically, the research investigated the influence of sewage sludge biochar (SSBC) on the accumulation of Cd into rice (Oryza sativa L.) grown in Cd contaminated (0.82 +/- 0.07 mg/kg) paddy soil. Results indicated, Cd concentrations in rice grains to significantly (p < 0.05) decrease from 1.35 +/- 0.09 mg/kg in the control to 0.82 +/- 0.07 mg/kg and 0.80 +/- 0.21 mg/kg in the 1.5 t/ha and 3.0 t/ha treatments, respectively. Accordingly, the hazardous quotient (HQ) indices for Cd, associated with rice grain consumption, were also reduced by ~40%. SSBC amendment significantly (p < 0.05) increased grain yields from 1.90 +/- 0.08 g/plant in the control to 2.17 +/- 0.30 g/plant and 3.40 +/- 0.27 g/plant in the 1.5 t/ha and 3.0 t/ha treatments, respectively. Thus, the amendment of SSBC to contaminated paddy soils, even at low application rates, could be an effective approach to mitigate Cd accumulation into rice plants, to improve rice grain yields, and to thereby improve food security and protect public health. PMID- 27368133 TI - Good Eating Makes Good Reading. PMID- 27368134 TI - Bonne lecture, bonne alimentation. PMID- 27368132 TI - Knockdown delta-5-desaturase promotes the formation of a novel free radical byproduct from COX-catalyzed omega-6 peroxidation to induce apoptosis and sensitize pancreatic cancer cells to chemotherapy drugs. AB - Recent research has demonstrated that colon cancer cell proliferation can be suppressed in the cells that overexpress COX-2 via generating 8-hydroxyoctanoic acid (a free radical byproduct) during dihomo-gamma-linolenic acid (DGLA, an omega-6 fatty acid) peroxidation from knocking down cellular delta-5-desaturase (D5D, the key enzyme for converting DGLA to the downstream omega-6, arachidonic acid). Here, this novel research finding is extended to pancreatic cancer growth, as COX-2 is also commonly overexpressed in pancreatic cancer. The pancreatic cancer cell line, BxPC-3 (with high COX-2 expression and mutated p53), was used to assess not only the inhibitory effects of the enhanced formation of 8 hydroxyoctanoic acid from cellular COX-2-catalyzed DGLA peroxidation but also its potential synergistic and/or additive effect on current chemotherapy drugs. This work demonstrated that, by inducing DNA damage through inhibition of histone deacetylase, a threshold level of 8-hydroxyoctanoic acid achieved in DGLA-treated and D5D-knockdown BxPC-3 cells subsequently induce cancer cell apoptosis. Furthermore, it was shown that a combination of D5D knockdown along with DGLA treatment could also significantly sensitize BxPC-3 cells to various chemotherapy drugs, likely via a p53-independent pathway through downregulating of anti apoptotic proteins (e.g., Bcl-2) and activating pro-apoptotic proteins (e.g., caspase 3, -9). This study reinforces the supposition that using commonly overexpressed COX-2 for molecular targeting, a strategy conceptually distinct from the prevailing COX-2 inhibition strategy used in cancer treatment, is an important as well as viable alternative to inhibit cancer cell growth. Based on the COX-2 metabolic cascade, the outcomes presented here could guide the development of a novel omega-6-based dietary care strategy in combination with chemotherapy for pancreatic cancer. PMID- 27368135 TI - Canadian Consensus on Female Nutrition: Adolescence, Reproduction, Menopause, and Beyond. AB - OBJECTIVES: To provide health care professionals in Canada with the basic knowledge and tools to provide nutrition guidance to women through their lifecycle. OUTCOMES: Optimal nutrition through the female lifecycle was evaluated, with specific focus on adolescence, pre-conception, pregnancy, postpartum, menopause, and beyond. The guideline begins with an overview of guidance for all women, followed by chapters that examine the evidence and provide recommendations for the promotion of healthy nutrition and body weight at each life stage. Nutrients of special concern and other considerations unique to each life stage are discussed in each chapter. EVIDENCE: Published literature, governmental and health agency reports, clinical practice guidelines, grey literature, and textbook sources were used in supporting the recommendations made in this document. VALUES: The quality of evidence was rated using the criteria described in the report of the Canadian Task Force on Preventive Health Care. CHAPTER 2: GENERAL FEMALE NUTRITION: Summary Statements Recommendations CHAPTER 3: ADOLESCENCE NUTRITION: Summary Statements Recommendations CHAPTER 4: PRE CONCEPTUAL NUTRITION: Summary Statement Recommendations CHAPTER 5: NUTRITION IN PREGNANCY: Summary Statements Recommendations CHAPTER 6: POSTPARTUM NUTRITION AND LACTATION: Summary Statements Recommendations CHAPTER 7: NUTRITION DURING MENOPAUSE AND BEYOND: Summary Statement Recommendations. PMID- 27368136 TI - Consensus canadien sur la nutrition feminine : adolescence, reproduction, menopause et au-dela. AB - OBJECTIFS: Doter les professionnels de la sante du Canada de connaissances et d'outils de base, afin qu'ils puissent prodiguer des conseils nutritionnels aux femmes tout au long de leur cycle de vie. ReSULTATS: L'alimentation optimale a fait l'objet d'une evaluation tout au long du cycle de vie de la femme. Elle a porte en particulier sur l'adolescence, la preconception, la grossesse, la periode post-partum, la menopause et au-dela. Le present guide fournit d'abord des directives abregees a l'intention de toutes les femmes. Elles sont suivies de chapitres proposant un examen des donnees probantes, ainsi que des recommandations sur la promotion d'une alimentation saine et d'un poids sante a chaque etape de la vie. Par ailleurs, tous les chapitres presentent une analyse de nutriments d'interet particulier, ainsi que d'autres aspects uniques a chaque etape de la vie. DONNeES PROBANTES: Des documents publies, des rapports d'organismes gouvernementaux et de sante, des lignes directrices de pratique clinique, de la documentation parallele et des extraits de manuels ont servi a etayer les recommandations formulees dans le present document. VALEURS: L'evaluation de la qualite des donnees probantes repose sur les criteres decrits dans le rapport du Groupe d'etude canadien sur les soins de sante preventifs. CHAPITRE 2 : CONSEILS GeNeRAUX SUR L'ALIMENTATION FeMININE: Declarations Sommaires Recommandations CHAPITRE 3 : ALIMENTATION DE L'ADOLESCENTE: Declarations Sommaires Recommandations CHAPITRE 4 : ALIMENTATION PReCONCEPTIONNELLE: Declarations Sommaires Recommandations CHAPITRE 5 : ALIMENTATION PENDANT LA GROSSESSE: Declarations Sommaires Recommandations CHAPITRE 6 : ALIMENTATION ET LACTATION POST-PARTUM: Declarations Sommaires Recommandations CHAPITRE 7 : ALIMENTATION PENDANT LA MeNOPAUSE ET AU-DELa: Declarations Sommaires Recommandations. PMID- 27368137 TI - Plant acyl-CoA-binding proteins: An emerging family involved in plant development and stress responses. AB - Acyl-CoA-binding protein (ACBP) was first identified in mammals as a neuropeptide, and was demonstrated to belong to an important house-keeping protein family that extends across eukaryotes and some prokaryotes. In plants, the Arabidopsis ACBP family consists of six AtACBPs (AtACBP1 to AtACBP6), and has been investigated using gene knock-out mutants and overexpression lines. Herein, recent findings on the AtACBPs are examined to provide an insight on their functions in various plant developmental processes, such as embryo and seed development, seed dormancy and germination, seedling development and cuticle formation, as well as their roles under various environmental stresses. The significance of the AtACBPs in acyl-CoA/lipid metabolism, with focus on their interaction with long to very-long-chain (VLC) acyl-CoA esters and their potential role in the formation of lipid droplets in seeds and vegetative tissues are discussed. In addition, recent findings on the rice ACBP family are presented. The similarities and differences between ACBPs from Arabidopsis and rice, that represent eudicot and monocot model plants, respectively, are analyzed and the evolution of plant ACBPs by phylogenetic analysis reviewed. Finally, we propose potential uses of plant ACBPs in phytoremediation and in agriculture related to the improvement of environmental stress tolerance and seed oil production. PMID- 27368138 TI - [Hydatidosis bone wall chest: About three cases]. AB - INTRODUCTION: Bone hydatidosis of the chest wall is rarely reported in the literature. Costal and sternal location are uncommon. Through 3 observations and literature review, we report particular pathophysiological and diagnostic aspects of costal and sternal hydatidosis. We also discuss therapeutic and prognostic aspects of this disease. OUR CASES: we report the cases of 45, 41 and 17 years old male patients, 2 of them had previous surgery for thoracic wall mass in general surgery service. Clinical presentation was thoracic wall painful mass sticking to bone. One patient had isolated costal location, the 2 others had sternal location; in one of them, the disease is located in sterno-costo clavicular area. In all 3 cases, the disease was diagnosed by computed tomography (CT) scan, showing bone lysis or mediastinum enlargement. Patients undergo extended bone resection removing away all destructed parts of the bone. After surgery, albendazole has been prescribed to all patients. No recurrence was observed after 12 months follow-up. CONCLUSION: Chest wall bone hydatidosis is unusual even in endemic regions, with slow evolution and inconspicuous symptoms. Radiology plays a key role in the management of this disease. Extended surgical resection associated with medical treatment (albendazole) is a reliable treatment without recurrence. PMID- 27368139 TI - [Multiple pulmonary opacities revealing toxocariasis]. AB - INTRODUCTION: Toxocariasis is a parasitosis which complicates the accidental infestation of the humans by larvae of a roundworms belonging of the genus Toxocara. In adults, the discovery is often incidental during a hypereosinophilia check-up. Clinical signs are not specific and depend on affected organs. CASE REPORT: We report the case of a 53-year-old-woman who has consulted for a recent cough, after spontaneous resolution of abdominal pain. The laboratory examination isolated an hypereosinophilia and the liver sonography showed two hypoechogenic nodules. The CT-scan found bilateral lung nodules with ground glass halo. Broncho alveolar lavage identified an eosinophilic alveolitis. Positive serologic results for toxocariasis and western blot results allowed to conclude to the diagnosis of pulmonary and hepatic toxocariasis. CONCLUSION: Although rare, pulmonary toxocariasis should be suspect in any lung eosinophilia, especially if the patient has never traveled. PMID- 27368141 TI - Editorial Comment. PMID- 27368142 TI - Editorial Comment. PMID- 27368140 TI - Oxidized cholesteryl esters and inflammation. AB - The oxidation hypothesis of atherosclerosis proposes that oxidized LDL is a major causative factor in the development of atherosclerosis. Although this hypothesis has received strong mechanistic support and many animal studies demonstrated profound atheroprotective effects of antioxidants, which reduce LDL oxidation, the results of human clinical trials with antioxidants were mainly negative, except in selected groups of patients with clearly increased systemic oxidative stress. We propose that even if reducing lipoprotein oxidation in humans might be difficult to achieve, deeper understanding of mechanisms by which oxidized LDL promotes atherosclerosis and targeting these specific mechanisms will offer novel approaches to treatment of cardiovascular disease. In this review article, we focus on oxidized cholesteryl esters (OxCE), which are a major component of minimally and extensively oxidized LDL and of human atherosclerotic lesions. OxCE and OxCE-protein covalent adducts induce profound biological effects. Among these effects, OxCE activate macrophages via toll-like receptor-4 (TLR4) and spleen tyrosine kinase and induce macropinocytosis resulting in lipid accumulation, generation of reactive oxygen species and secretion of inflammatory cytokines. Specific inhibition of OxCE-induced TLR4 activation, as well as blocking other inflammatory effects of OxCE, may offer novel treatments of atherosclerosis and cardiovascular disease. This article is part of a Special Issue entitled: Lipid modification and lipid peroxidation products in innate immunity and inflammation edited by Christoph J. Binder. PMID- 27368143 TI - Near-Infrared Ag2S Quantum Dots-Based DNA Logic Gate Platform for miRNA Diagnostics. AB - Dysregulation of miRNA expression is correlated with the development and progression of many diseases. These miRNAs are regarded as promising biomarkers. However, it is challenging to measure these low abundant molecules without employing time-consuming radioactive labeling or complex amplification strategies. Here, we present a DNA logic gate platform for miRNA diagnostics with fluorescence outputs from near-infrared (NIR) Ag2S quantum dots (QDs). Carefully designed toehold exchange-mediated strand displacements with different miRNA inputs occur on a solid-state interface, which control QDs release from solid state interface to solution, responding to multiplex information on initial miRNAs. Excellent fluorescence emission properties of NIR Ag2S QDs certify the great prospect for amplification-free and sensitive miRNA assay. We demonstrate the potential of this platform by achieving femtomolar level miRNA analysis and the versatility of a series of logic circuits computation. PMID- 27368144 TI - Queries for the article entitled "Predictors for extensive nodal involvement in breast cancer patients with axillary lymph node metastases". PMID- 27368145 TI - Far-red light photoacclimation: Chromophorylation of FR induced alpha- and beta subunits of allophycocyanin from Chroococcidiopsis thermalis sp. PCC7203. AB - Cyanobacterial light-harvesting complexes, phycobilisomes, can undergo extensive remodeling under varying light conditions. Acclimation to far-red light involves not only generation of red-shifted chlorophylls in the photosystems, but also induction of additional copies of core biliproteins that have been related to red shifted components of the phycobilisome (Gan et al., Life 5, 4, 2015). We are studying the molecular basis for these acclimations in Chroococcidiopsis thermalis sp. PCC7203. Five far-red induced allophycocyanin subunits (ApcA2, ApcA3, ApcB2, ApcB3 and ApcF2) were expressed in Escherichia coli, together with S-type chromophore-protein lyases and in situ generated chromophore, phycocyanobilin. Only one subunit, ApcF2, shows an unusual red-shift (lambdaAmax~675nm, lambdaFmax~698nm): it binds the chromophore non-covalently, thereby preserving its full conjugation length. This mechanism operates also in two Cys-variants of the induced subunits of bulky APC. All other wild-type subunits bind phycocyanobilin covalently to the conventional Cys-81 under catalysis of the lyase, CpcS1. Although three of them also show binding to additional cysteines, all absorb and fluoresce similar to conventional APC subunits (lambdaAmax~610nm, lambdaFmax~640nm). Another origin of red-shifted complexes was identified, however, when different wild-type alpha- and beta subunits of the far-red induced bulky APC were combined in a combinatorial fashion. Strongly red-shifted complexes (lambdaFmax<=722nm) were formed when the alpha-subunit, PCB-ApcA2, and the beta-subunit, PCB-ApcB2, were generated together in E. coli. This extreme aggregation-induced red-shift of ~90nm of covalently bound chromophores is reminiscent, but much larger, than the ~30nm observed with conventional APC. PMID- 27368146 TI - Exploring the role of the patient-physician relationship on insulin adherence and clinical outcomes in type 2 diabetes: Insights from the MOSAIc study. AB - BACKGROUND: The 2-year prospective MOSAIc (Multinational Observational Study assessing Insulin use: understanding the challenges associated with progression of therapy) study is investigating whether patient-, physician-, and health system-related factors affect outcomes in patients with type 2 diabetes (T2D). This baseline subanalysis investigated how aspects of the patient-physician relationship are associated with diabetes-related distress, insulin adherence, and glycemic control. METHODS: Patients with T2D taking insulin for >=3 months were recruited at primary care and specialty practice sites in 18 countries. Physicians provided usual care. Clinical history and most recent HbA1c values were collected; patients were surveyed regarding their perception of physician interactions, diabetes-related distress level, and insulin adherence. RESULTS: The analysis population comprised 4341 patients. Four (of six) domains showed a significant relationship with total diabetes-related distress (P < 0.01). Poor insulin adherence was associated with greater diabetes-related distress (adjusted odds ratio [aOR] 1.14; 95% confidence interval [CI] 1.06-1.22), higher Discrimination (aOR 1.13; 95% CI 1.02-1.27) and Hurried Communication (aOR 1.35; 95% CI 1.20-1.53) scores, and a lower Explained Results score (aOR 0.86; 95% CI 0.77-0.97). Poor insulin adherence was associated with a 0.43% increase in HbA1c, whereas a 1-unit increase in total diabetes-related distress and Hurried Communication scores was associated with a 0.171% and 0.145% increase in HbA1c, respectively. CONCLUSIONS: Patients distressed about living with T2D, and dissatisfied with aspects of their interactions with physicians, exhibited poor insulin adherence. Perceived physician inattention and lack of engagement (and diabetes-related distress) directly affect insulin adherence and glycemic control. PMID- 27368147 TI - Aromatized testosterone attenuates contextual generalization of fear in male rats. AB - Generalization is a common symptom of many anxiety disorders, and females are 60% more likely to suffer from an anxiety disorder than males. We have previously demonstrated that female rats display significantly accelerated rates of contextual fear generalization compared to male rats; a process driven, in part, by activation of ERbeta. The current study was designed to determine the impact of estrogens on contextual fear generalization in male rats. For experiment 1, adult male rats were gonadectomized (GDX) and implanted with a capsule containing testosterone proprionate, estradiol, dihydrotestosterone proprionate (DHT), or an empty capsule. Treatment with testosterone or estradiol maintained memory precision when rats were tested in a different (neutral) context 1day after training. However, male rats treated with DHT or empty capsules displayed significant levels of fear generalization, exhibiting high levels of fear in the neutral context. In Experiment 2, we used acute injections of gonadal hormones at a time known to elicit fear generalization in female rats (e.g. 24h before testing). Injection treatment followed the same pattern of results seen in Experiment 1. Finally, animals given daily injections of the aromatase inhibitor, Fadrozole, displayed significant fear generalization. These data suggest that testosterone attenuates fear generalization likely through the aromatization testosterone into estradiol as animals treated with the non-aromatizable androgen, DHT, or animals treated with Fadrozole, displayed significant generalized fear. Overall, these results demonstrate a sex-dependent effect of estradiol on the generalization of contextual fear. PMID- 27368148 TI - Brain CRF-binding protein modulates aspects of maternal behavior under stressful conditions and supports a hypo-anxious state in lactating rats. AB - Reduced corticotropin-releasing factor (CRF) receptor activation in the postpartum period is essential for adequate maternal behavior. One of the factors contributing to this hypo-activity might be the CRF-binding protein (CRF-BP), which likely reduces the availability of free extracellular CRF/urocortin 1. Here, we investigated behavioral effects of acute CRF-BP inhibition using 5MUg of CRF(6-33) administered either centrally or locally within different parts of the bed nucleus of the stria terminalis (BNST) in lactating rats. Additionally, we assessed CRF-BP expression in the BNST comparing virgin and lactating rats. Central CRF-BP inhibition increased maternal aggression during maternal defense but did not affect maternal care or anxiety-related behavior. CRF-BP inhibition in the medial-posterior BNST had no effect on maternal care under non-stress conditions but impaired the reinstatement of maternal care following stressor exposure. Furthermore, maternal aggression, particularly threat behavior, and anxiety-related behavior were elevated by CRF-BP inhibition in the medial posterior BNST. In the anterior-dorsal BNST, CRF-BP inhibition increased only non maternal behaviors following stress. Finally, CRF-BP expression was higher in the anterior compared to the posterior BNST but was not different between virgin and lactating rats in either region. Our study demonstrates a key role of the CRF-BP, particularly within the BNST, in modulating CRF's impact on maternal behavior. The CRF-BP is important for the reinstatement of maternal care after stress, for modulating threat behavior during an aggressive encounter and for maintaining a hypo-anxious state during lactation. Thus, the CRF-BP likely contributes to the postpartum-associated down-regulation of the CRF system in a brain region dependent manner. PMID- 27368150 TI - Efficacy and safety of bupivacaine versus lidocaine in local anesthesia of the nasopharynx: A meta-analysis. AB - PURPOSE: To assess the efficacy and safety of bupivacaine compared with lidocaine in local anesthesia of nasopharynx through meta-analysis. METHODS: A number of medical literature data bases were searched electronically. Relevant journals and references of included studies were manually searched. Two reviewers independently performed data extraction and quality assessment. RESULTS: Four studies were included. Visual analog scale (VAS) scores, acceptable discomfort, and bleeding scores were analyzed for bupivacaine versus lidocaine. When considering the VAS scores, bupivacaine as a local anesthetic agent was better than lidocaine in controlling the pain of postoperative patients (p < 0.00001). From VAS scores of patients for transnasal fiberoptic nasopharyngolaryngoscopic examination that was performed to evaluate upper airway structures, lidocaine was found to be better at pain management in patients who underwent transnasal endoscopic examination (p < 0.00001). However, when analyzing the acceptable discomfort of patients who underwent upper gastrointestinal endoscopy, which serves as a valuable tool to evaluate upper gastrointestinal structures, the patients in the bupivacaine group demonstrated a higher acceptable discomfort than the patients in the lidocaine group (p = 0.008). With regard to the bleeding scores of the patients with nasal surgery, lidocaine was better at bleeding in postoperative patients compared with bupivacaine (p = 0.0007). These results indicated that bupivacaine showed better pain control of postoperative patients and acceptable discomfort in patients with upper gastrointestinal endoscopy. Lidocaine had a significantly increased ability the pain of patients with transnasal fiberoptic nasopharyngolaryngoscopic examination and bleeding in postoperative patients. No systemic adverse events were reported. CONCLUSION: Bupivacaine was found to have better promotion to pain control than did lidocaine for the patients after nasal surgery. Lidocaine had a significantly increased inhibition of bleeding in these postoperative patients; however, the efficacy between bupivacaine and lidocaine was unclear for the patients who had transnasal endoscopic examinations. PMID- 27368149 TI - Expression of the MYB transcription factor gene BplMYB46 affects abiotic stress tolerance and secondary cell wall deposition in Betula platyphylla. AB - Plant MYB transcription factors control diverse biological processes, such as differentiation, development and abiotic stress responses. In this study, we characterized BplMYB46, an MYB gene from Betula platyphylla (birch) that is involved in both abiotic stress tolerance and secondary wall biosynthesis. BplMYB46 can act as a transcriptional activator in yeast and tobacco. We generated transgenic birch plants with overexpressing or silencing of BplMYB46 and subjected them to gain- or loss-of-function analysis. The results suggest that BplMYB46 improves salt and osmotic tolerance by affecting the expression of genes including SOD, POD and P5CS to increase both reactive oxygen species scavenging and proline levels. In addition, BplMYB46 appears to be involved in controlling stomatal aperture to reduce water loss. Overexpression of BplMYB46 increases lignin deposition, secondary cell wall thickness and the expression of genes in secondary cell wall formation. Further analysis indicated that BplMYB46 binds to MYBCORE and AC-box motifs and may directly activate the expression of genes involved in abiotic stress responses and secondary cell wall biosynthesis whose promoters contain these motifs. The transgenic BplMYB46-overexpressing birch plants, which have improved salt and osmotic stress tolerance, higher lignin and cellulose content and lower hemicellulose content than the control, have potential applications in the forestry industry. PMID- 27368151 TI - 5-lipoxygenase activation is involved in the mechanisms of chronic hepatic injury in a rat model of chronic aluminum overload exposure. AB - We previously confirmed that rats overloaded with aluminum exhibited hepatic function damage and increased susceptibility to hepatic inflammation. However, the mechanism of liver toxicity by chronic aluminum overload is poorly understood. In this study, we investigated changes in the 5-lipoxygenase (5-LO) signaling pathway and its effect on liver injury in aluminum-overloaded rats. A rat hepatic injury model of chronic aluminum injury was established via the intragastric administration of aluminum gluconate (Al(3+) 200mg/kg per day, 5days a week for 20weeks). The 5-LO inhibitor, caffeic acid (10 and 30mg/kg), was intragastrically administered 1h after aluminum administration. Hematoxylin and eosin staining was used to visualize pathological changes in rat liver tissue. A series of biochemical indicators were measured with biochemistry assay or ELISAs. Immunochemistry and RT-PCR methods were used to detect 5-LO protein and mRNA expression in the liver, respectively. Caffeic acid administration protected livers against histopathological injury, decreased plasma ALT, AST, and ALP levels, decreased TNF-alpha, IL-6, IL-1beta and LTs levels, increased the reactive oxygen species content, and down-regulated the mRNA and protein expressions of 5-LO in aluminum overloaded rats. Our results indicate that 5 lipoxygenase activation is mechanistically involved in chronic hepatic injury in a rat model of chronic aluminum overload exposure and that the 5-LO signaling pathway, which associated with inflammation and oxidative stress, is a potential therapeutic target for chronic non-infection liver diseases. PMID- 27368152 TI - Involvement of the histamine H4 receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells. AB - Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100MUM) and doxorubicin (0.2uM) decreased the cell survival rate, but olanzapine (1-100uM) did not. Under granulocytic differentiation for 5days, clozapine, even at a concentration of 25MUM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H4 receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H4 receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H4 receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H4 receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation. PMID- 27368154 TI - Novel full logistic model for estimation of the estrogenic activity of chemical mixtures. AB - Estrogenic compounds as well as other biologically active substances are commonly present in the form of complex mixtures in the environment. There is still no satisfactory model that would be capable of predicting the toxic effects of mixtures containing partial receptor agonists and compounds with different parameters of their dose-response curves. Therefore, a novel Full Logistic Model (FLM) of prediction using all the parameters of dose-response curves has been suggested and compared with previously published approaches. We tested the receptor-binding activities of selected estrogens including full and partial agonists and their mixtures using yeast reporter gene assays and the human T47D cell line. Combination effects were modeled with FLM and predicted curves were compared with the data obtained experimentally. FLM yielded a good fit to the experimental data from both the receptor-binding assays and gave better predictions than the previously published approaches. FLM also provided satisfactory results regarding final partial agonistic dose-response curves with maximum influenced by the inhibitory effect of the partial agonist. FLM is not limited by any simplification like the toxic equivalency factor approach or generalized concentration addition and therefore it could be employed for mixtures containing chemicals with different parameters of their dose-response curves (maximum, minimum, inflex point or slope). PMID- 27368153 TI - Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats. AB - Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to insulin resistance. We hypothesized that acute ozone-induced stress response and metabolic impairment would persist during subchronic episodic exposure and induce peripheral insulin resistance. Male Wistar Kyoto rats were exposed to air or 0.25ppm or 1.00ppm ozone, 5h/day, 3 consecutive days/week (wk) for 13wks. Pulmonary, metabolic, insulin signaling and stress endpoints were determined immediately after 13wk or following a 1wk recovery period (13wk+1wk recovery). We show that episodic ozone exposure is associated with persistent pulmonary injury and inflammation, fasting hyperglycemia, glucose intolerance, as well as, elevated circulating adrenaline and cholesterol when measured at 13wk, however, these responses were largely reversible following a 1wk recovery. Moreover, the increases noted acutely after ozone exposure in non-esterified fatty acids and branched chain amino acid levels were not apparent following a subchronic exposure. Neither peripheral or tissue specific insulin resistance nor increased hepatic gluconeogenesis were present after subchronic ozone exposure. Instead, long-term ozone exposure lowered circulating insulin and severely impaired glucose-stimulated beta-cell insulin secretion. Thus, our findings in young-adult rats provide potential insights into epidemiological studies that show a positive association between ozone exposures and type 1 diabetes. Ozone-induced beta-cell dysfunction may secondarily contribute to other tissue-specific metabolic alterations following chronic exposure due to impaired regulation of glucose, lipid, and protein metabolism. PMID- 27368155 TI - Mycobacteriosis caused by Mycobacterium marinum in reared mullets: first evidence from Sardinia (Italy). AB - Mycobacterium marinum is a slow-growing non-tuberculous mycobacterium, and it is considered the most common aetiologic agent of mycobacteriosis in wild and cultured fish. The diagnosis is principally made by histology when positive Ziehl Neelsen stain granulomas are detected. The aim of this study was to investigate the occurrence of mycobacteriosis in extensively cultured Mugilidae of two lagoons (Cabras and San Teodoro) from Sardinia by the use of histology, microbiology, PCR and DNA sequencing. Nine of 106 mullets examined were affected by mycobacteriosis, and the spleen was the most affected organ. The histology detected higher rate (100%) of infection in spleen than the culture and PCR (75% and 62.5%, respectively). The sequencing of hsp65 gene identified M. marinum as the primary cause of mycobacteriosis in the mullets examined. Mullets affected by mycobacteriosis were mainly fished in the San Teodoro lagoon characterized by critical environmental conditions. Histology remains the most common method in detecting fish affected by mycobacteriosis, and PCR-based methods are essential for species identification. Our finding are worthy of attention because mycobacteriosis caused by M. marinum in reared mullets was evidenced for the first time in Sardinia, suggesting that this disease may be underestimated also in other cultured fish species. PMID- 27368156 TI - Propofol attenuates high glucose-induced superoxide anion accumulation in human umbilical vein endothelial cells. AB - Perioperative hyperglycemia is a common clinical metabolic disorder. Hyperglycemia could induce endothelial apoptosis, dysfunction, and inflammation, resulting in endothelial injury. Propofol is a widely used anesthetic drug in clinical settings. Our previous studies indicated that propofol attenuated high glucose-induced endothelial apoptosis, dysfunction, and inflammation via inhibiting reactive oxygen species (ROS) accumulation. However, the mechanisms by which propofol reduces high glucose-induced endothelial ROS accumulation are still obscure. In this study, we examined how propofol attenuates high glucose induced endothelial ROS accumulation. Compared with 5 mm glucose treatment, 15 mm glucose upregulated the expression of pin-1, phosphatase A2 (PP2A), p66shc and mitochondrial p66shc expression, increased p66shc -Ser36 phosphorylation, and O2. accumulation. More importantly, although propofol had no effect on 15 mm glucose induced p66shc -Ser36 phosphorylation and pin-1 expression, propofol could downregulated PP2A expression and p66shc expression in whole-cell and mitochondrion, resulting in the reduction of O2.- accumulation. Moreover, we demonstrated that the antioxidative effect of propofol was similar to that of calyculin A, an inhibitor of PP2A. In contrast, FTY720, an activator of PP2A, antagonized the effect of propofol. Our data indicated that the antioxidative effect of propofol was achieved by downregulating PP2A expression, resulting in the inhibition of p66shc -Ser36 dephosphorylation and mitochondrial p66shc expression. PMID- 27368157 TI - Metabolic syndrome in white European men presenting for primary couple's infertility: investigation of the clinical and reproductive burden. AB - Despite complex interactions between obesity, dyslipidemia, hyperinsulinaemia, and the reproductive axis, the impact of metabolic syndrome on human male reproductive function has not been analysed comprehensively. Complete demographic, clinical, and laboratory data from 1337 consecutive primary infertile men were analysed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (categorised 0 vs. 1 vs. 2 or higher). NCEP-ATPIII criteria were used to define metabolic syndrome. Semen analysis values were assessed based on the 2010 World Health Organisation (WHO) reference criteria. Descriptive statistics and logistic regression models tested the association between semen parameters and clinical characteristics and metabolic syndrome. Metabolic syndrome was found in 128 (9.6%) of 1337 men. Patients with metabolic syndrome were older (p < 0.001) and had a greater Charlson Comorbidity Index of 1 or higher (chi-square: 15.6; p < 0.001) compared with those without metabolic syndrome. Metabolic syndrome patients had lower levels of total testosterone (p < 0.001), sex hormone-binding globulin (p = 0.004), inhibin B (p = 0.03), and anti Mullerian hormone (p = 0.009), and they were hypogonadal at a higher rate (chi square: 32.0; p < 0.001) than patients without metabolic syndrome. Conversely, the two groups did not differ significantly in further hormonal levels, semen parameters, and rate of either obstructive or non-obstructive azoospermia. At multivariate logistic regression analysis, testicular volume (OR: 0.90; p = 0.002) achieved independent predictor status for WHO pathological semen concentration; conversely, age, Charlson Comorbidity Index scores, metabolic syndrome, and inhibin B values did not. No parameters predicted normal sperm morphology and total progressive motility. Metabolic syndrome accounts for roughly 9% of men presenting for primary couple's infertility. Although metabolic syndrome patients have a lower general male health status, semen analysis values seem independent of the presence of metabolic syndrome. PMID- 27368158 TI - Liver transplantation for biliary atresia: A nationwide investigation from 1996 to 2013 in mainland China. AB - We investigated the overall situation of LT for BA in mainland China and analyzed their survival outcomes based on data from CLTR. Between January 1996 and December 2013, 509 liver transplants for BA were performed in mainland China and were included in this study. Patients' median age was 9.6 months (range: 4.8 175.2 months). KP was previously performed in 194 cases (38.1%). Grafts from living donors were used in 380 cases (74.7%). Era I (1996.1-2010.12) and era II (2011.1-2013.12) comprised 151 cases (29.7%) and 358 cases (70.3%), respectively. Twenty-five centers had performed at least one liver transplant for children with BA. Centers from Shanghai (197 cases), Tianjin (143 cases) and Beijing (81 cases) involved 82.7% of the 509 cases. One- and five-yr graft survival rates were 84.7% and 72.6%, respectively. Split grafts, center volume <20, GRWR >=4.0%, and steroid-free immunosuppression regimen were independent risk factors for graft survival. In conclusion, the dramatic expansion of pediatric liver transplant programs in mainland China has enabled improved survival for those children affected by this devastating disease. However, screening of BA in neonates should be emphasized throughout the country to enhance early referrals for KP. PMID- 27368159 TI - The use of patch tests in the diagnosis of delayed hypersensitivity drug eruptions. AB - BACKGROUND: Adverse drug reactions (ADRs) are common. In the absence of a sufficiently sensitive and specific laboratory test, identification of the culprit drug remains a diagnostic challenge. Patch tests have recently been advocated as a means of detecting drug sensitivity. OBJECTIVE: To further elucidate the usefulness of patch tests in revealing the causative drugs of cutaneous ADRs (CADRs). MATERIALS AND METHODS: We conducted a non-blinded, prospective, controlled clinical trial. Twenty-five patients with a history of CADRs were patch tested, and 25 healthy subjects who had never experienced CADRs served as controls. RESULTS: A morbilliform eruption was the most frequent skin reaction. Patch tests were positive in eight of the 25 patients with CADR (32%). Specifically, five of the 13 patients with morbilliform drug eruption (38.4%) tested positive, as did one of the four patients with erythema multiforme/Stevens Johnson syndrome (25%), and one of the two patients with the drug reaction with eosinophilia and systemic symptoms syndrome. Antibiotics and anticonvulsants resulted in positive patch tests most often. Patch test sensitivity was 32%, specificity was 92%, and negative and positive predictive values were 57.5% and 80%, respectively. Significant correlation was found between the patch test result and the clinical probability of a CADR according to the imputability score of the drug. CONCLUSIONS: Patch testing for drugs causing ADRs shows high specificity rates even though the sensitivity is low. Such tests may therefore be useful in supporting the diagnosis of delayed-type CADRs, particularly when antibiotics or anticonvulsants are involved and the cutaneous reaction is a morbilliform rash. PMID- 27368160 TI - Impact of using artemisinin-based combination therapy (ACT) in the treatment of uncomplicated malaria from Plasmodium falciparum in a non-endemic zone. AB - BACKGROUND: Artemisinin-based combination therapy (ACT) has been adopted by the World Health Organization as a first-line treatment for uncomplicated Plasmodium falciparum malaria. In endemic regions, it has proven more effective in treating the disease, and even in reducing its transmission. Nonetheless, there is a scarcity of studies carried out in non-endemic areas on imported uncomplicated malaria. METHODS: This is a retrospective, observational study performed on patients diagnosed and admitted with uncomplicated P. falciparum malaria between 2004 and 2015. The objective was to compare the parasite clearance period and the average hospital length of stay for patients treated with ACT vs those receiving other treatment regimens. RESULTS: Eighty-five patients were included in the study. Fifty-one received ACT treatment (dihydroartemisinin-piperaquine) and thirty-four patients were treated with quinine sulfate+doxycycline or atovaquone/proguanil. The parasite clearance period was shorter in the group of patients treated with ACT compared to those receiving other treatment types: 24 h (IQR 24) vs 48 h (IQR 48), p < 0.01. The average hospital stay was also shorter in the ACT group with respect to the second group: 2.67 days (IQR 1.08) vs 3.96 days (IQR 2.87), p < 0.001. A mild case of hepatitis was registered in the group treated with ACT. CONCLUSIONS: ACT treatment of admitted hospital patients with imported uncomplicated malaria from P. falciparum reduced the days spent hospitalized as well as producing a more rapid parasite clearance compared to classic treatment. In spite of being treated with safe medications, one has to be alert to possible adverse effects such as hepatitis and delayed haemolytic anaemia. PMID- 27368161 TI - Adhesion kinetics of human primary monocytes, dendritic cells, and macrophages: Dynamic cell adhesion measurements with a label-free optical biosensor and their comparison with end-point assays. AB - Monocytes, dendritic cells (DCs), and macrophages (MFs) are closely related immune cells that differ in their main functions. These specific functions are, to a considerable degree, determined by the differences in the adhesion behavior of the cells. To study the inherently and essentially dynamic aspects of the adhesion of monocytes, DCs, and MFs, dynamic cell adhesion assays were performed with a high-throughput label-free optical biosensor [Epic BenchTop (BT)] on surfaces coated with either fibrinogen (Fgn) or the biomimetic copolymer PLL-g PEG-RGD. Cell adhesion profiles typically reached their maximum at ~60 min after cell seeding, which was followed by a monotonic signal decrease, indicating gradually weakening cell adhesion. According to the biosensor response, cell types could be ordered by increasing adherence as monocytes, MFs, and DCs. Notably, all three cell types induced a larger biosensor signal on Fgn than on PLL-g-PEG-RGD. To interpret this result, the molecular layers were characterized by further exploiting the potentials of the biosensor: by measuring the adsorption signal induced during the surface coating procedure, the authors could estimate the surface density of adsorbed molecules and, thus, the number of binding sites potentially presented for the adhesion receptors. Surfaces coated with PLL-g-PEG-RGD presented less RGD sites, but was less efficient in promoting cell spreading than those coated with Fgn; hence, other binding sites in Fgn played a more decisive role in determining cell adherence. To support the cell adhesion data obtained with the biosensor, cell adherence on Fgn-coated surfaces 30-60 min after cell seeding was measured with three complementary techniques, i.e., with (1) a fluorescence-based classical adherence assay, (2) a shear flow chamber applying hydrodynamic shear stress to wash cells away, and (3) an automated micropipette using vacuum-generated fluid flow to lift cells up. These techniques confirmed the results obtained with the high-temporal-resolution Epic BT, but could only provide end-point data. In contrast, complex, nonmonotonic cell adhesion kinetics measured by the high-throughput optical biosensor is expected to open a window on the hidden background of the immune cell extracellular matrix interactions. PMID- 27368162 TI - Seroprevalence of Toscana virus in dogs from Corsica, France. AB - BACKGROUND: Toscana virus (TOSV) is an arbovirus belonging to the Bunyaviridae, a family of negative-stranded, enveloped RNA viruses. The virus can be transmitted to humans through the bite of an infected female sand fly of the genus Phlebotomus. Infections are usually asymptomatic but the virus is known to cause aseptic meningitis and/or meningo-encephalitis in the Mediterranean countries. Dogs are good sentinels for detection of viral circulation and are more easily accessible than wild animals. FINDINGS: In 2013 and 2014, we collected sera from 231 adult dogs living in 26 counties in two departments in Corsica, a French island in the Mediterranean. The virus microneutralization-based seroprevalence assay revealed a seropositivity of 3.9 % dogs on the eastern coast of Corsica. CONCLUSIONS: Our study confirms the circulation of TOSV in Corsica. Accordingly, in geographical areas where dogs possess TOSV neutralizing antibodies, direct and indirect TOSV diagnosis should be implemented in patients presenting with febrile illnesses and central nervous system infections such as meningitis and encephalitis. PMID- 27368164 TI - Association of alkali metal cations with phosphatidylcholine liposomal membrane surface. AB - Interactions of alkali metal cations (Li+, Na+, K+, Cs+) with phosphatidylcholine (PC) liposomal membranes were investigated through experimental studies and theoretical considerations. Using a microelectrophoresis technique, charge densities of experimental membrane surfaces were measured as a function of the pH of electrolyte solutions. Equilibria between the PC liposomal membranes and monovalent ions were mathematically analyzed and described quantitatively through a previously proposed theoretical model. Association constants between functional groups of PC and the studied ions were determined and used to define theoretical curves of membrane surface charge density versus pH. Theoretical and experimental data were compared to verify the model. The PC membrane was found to have the highest affinity for lithium ions, among the ions tested. PMID- 27368163 TI - Determinants of FIV and HIV Vif sensitivity of feline APOBEC3 restriction factors. AB - BACKGROUND: Feline immunodeficiency virus (FIV) is a global pathogen of Felidae species and a model system for Human immunodeficiency virus (HIV)-induced AIDS. In felids such as the domestic cat (Felis catus), APOBEC3 (A3) genes encode for single-domain A3Z2s, A3Z3 and double-domain A3Z2Z3 anti-viral cytidine deaminases. The feline A3Z2Z3 is expressed following read-through transcription and alternative splicing, introducing a previously untranslated exon in frame, encoding a domain insertion called linker. Only A3Z3 and A3Z2Z3 inhibit Vif deficient FIV. Feline A3s also are restriction factors for HIV and Simian immunodeficiency viruses (SIV). Surprisingly, HIV-2/SIV Vifs can counteract feline A3Z2Z3. RESULTS: To identify residues in feline A3s that Vifs need for interaction and degradation, chimeric human-feline A3s were tested. Here we describe the molecular direct interaction of feline A3s with Vif proteins from cat FIV and present the first structural A3 model locating these interaction regions. In the Z3 domain we have identified residues involved in binding of FIV Vif, and their mutation blocked Vif-induced A3Z3 degradation. We further identified additional essential residues for FIV Vif interaction in the A3Z2 domain, allowing the generation of FIV Vif resistant A3Z2Z3. Mutated feline A3s also showed resistance to the Vif of a lion-specific FIV, indicating an evolutionary conserved Vif-A3 binding. Comparative modelling of feline A3Z2Z3 suggests that the residues interacting with FIV Vif have, unlike Vif-interacting residues in human A3s, a unique location at the domain interface of Z2 and Z3 and that the linker forms a homeobox-like domain protruding of the Z2Z3 core. HIV 2/SIV Vifs efficiently degrade feline A3Z2Z3 by possible targeting the linker stretch connecting both Z-domains. CONCLUSIONS: Here we identified in feline A3s residues important for binding of FIV Vif and a unique protein domain insertion (linker). To understand Vif evolution, a structural model of the feline A3 was developed. Our results show that HIV Vif binds human A3s differently than FIV Vif feline A3s. The linker insertion is suggested to form a homeo-box domain, which is unique to A3s of cats and related species, and not found in human and mouse A3s. Together, these findings indicate a specific and different A3 evolution in cats and human. PMID- 27368166 TI - Bacteriopheophytin triplet state in Rhodobacter sphaeroides reaction centers. AB - It is well established that photoexcitation of Rhodobacter sphaeroides reaction centers (RC) with reduced quinone acceptors results in the formation of a triplet state localized on the primary electron donor P with a significant yield. The energy of this long-lived and therefore potentially damaging excited state is then efficiently quenched by energy transfer to the RC spheroidenone carotenoid, with its subsequent decay to the ground state by intersystem crossing. In this contribution, we present a detailed transient absorption study of triplet states in a set of mutated RCs characterized by different efficiencies of triplet formation that correlate with lifetimes of the initial charge-separated state P(+)H A (-) . On a microsecond time scale, two types of triplet state were detected: in addition to the well-known spheroidenone triplet state with a lifetime of ~4 MUs, in some RCs we discovered a bacteriopheophytin triplet state with a lifetime of ~40 MUs. As expected, the yield of the carotenoid triplet increased approximately linearly with the lifetime of P(+)H A (-) , reaching the value of 42 % for one of the mutants. However, surprisingly, the yield of the bacteriopheophytin triplet was the highest in RCs with the shortest P(+)H A (-) lifetime and the smallest yield of carotenoid triplet. For these the estimated yield of bacteriopheophytin triplet was comparable with the yield of the carotenoid triplet, reaching a value of ~7 %. Possible mechanisms of formation of the bacteriopheophytin triplet state are discussed. PMID- 27368165 TI - Thylakoid membrane model of the Chl a fluorescence transient and P700 induction kinetics in plant leaves. AB - A new Thylakoid model is presented, which describes in detail the electron/proton transfer reactions between membrane protein complexes including photosystems II and I (PSII, PSI), cytochrome (Cyt) b 6 f, mobile plastoquinone PQ pool in the thylakoid membrane, plastocyanin in lumen and ferredoxin in stroma, reduction of NADP via FNR and cyclic electron transfer. The Thylakoid model parameters were fitted both to Chl fluorescence induction data (FI) and oxido-reductions of P700 (DeltaA 810) measured from 20 MUs up to 20 s in pea leaves. The two-wave kinetics of FI and DeltaA 810 (O(JI)PSM and OABCDE) were described quantitatively, provided that the values of membrane electrochemical potential components DeltaPsi(t), pHL(t)/pHS(t) are in physiologically relevant ranges. The time courses on the time scale from nanoseconds to tens of seconds of oxido-reduction changes of ET components as well as concentrations of proton/ions (K+, Cl-) were calculated. We assume a low constant FNR activity over this period. Charge movements across the thylakoid membrane by passive leakage and active ATPase transport and proton buffer reactions are simulated. The dynamics of charge fluxes during photosynthetic induction under low light (PFD 200 MUmol photons m-2 s-1) were analyzed. The initial wave of P700 oxidation within 20 ms during independent operation of PSI and PSII was followed after 50 ms by PSI donor-side reduction from reduced PQ pool via Cyt b 6 f site. The Cyt b 6 f reactions contribute to the stabilization of fluxes in the time range 1 s < t < 10 s. The detailed analysis of Chl a fluorescence at the PSM stage (t > 10 s) would need the investigation of FNR activation effect in order to explain the transitions between cyclic and linear electron transport. PMID- 27368168 TI - [Not Available]. PMID- 27368169 TI - [Not Available]. PMID- 27368170 TI - [Not Available]. PMID- 27368167 TI - Comparison of human and mouse E-selectin binding to Sialyl-Lewis(x). AB - BACKGROUND: During inflammation, leukocytes are captured by the selectin family of adhesion receptors lining blood vessels to facilitate exit from the bloodstream. E-selectin is upregulated on stimulated endothelial cells and binds to several ligands on the surface of leukocytes. Selectin:ligand interactions are mediated in part by the interaction between the lectin domain and Sialyl-Lewis x (sLe(x)), a tetrasaccharide common to selectin ligands. There is a high degree of homology between selectins of various species: about 72 and 60 % in the lectin and EGF domains, respectively. In this study, molecular dynamics, docking, and steered molecular dynamics simulations were used to compare the binding and dissociation mechanisms of sLe(x) with mouse and human E-selectin. First, a mouse E-selectin homology model was generated using the human E-selectin crystal structure as a template. RESULTS: Mouse E-selectin was found to have a greater interdomain angle, which has been previously shown to correlate with stronger binding among selectins. sLe(x) was docked onto human and mouse E-selectin, and the mouse complex was found to have a higher free energy of binding and a lower dissociation constant, suggesting stronger binding. The mouse complex had higher flexibility in a few key residues. Finally, steered molecular dynamics was used to dissociate the complexes at force loading rates of 2000-5000 pm/ps(2). The mouse complex took longer to dissociate at every force loading rate and the difference was statistically significant at 3000 pm/ps(2). When sLe(x)-coated microspheres were perfused through microtubes coated with human or mouse E selectin, the particles rolled more slowly on mouse E-selectin. CONCLUSIONS: Both molecular dynamics simulations and microsphere adhesion experiments show that mouse E-selectin protein binds more strongly to sialyl Lewis x ligand than human E-selectin. This difference was explained by a greater interdomain angle for mouse E-selectin, and greater flexibility in key residues. Future work could introduce similar amino acid substitutions into the human E-selectin sequence to further modulate adhesion behavior. PMID- 27368171 TI - [Not Available]. PMID- 27368172 TI - [Not Available]. PMID- 27368173 TI - [Not Available]. PMID- 27368175 TI - [Not Available]. PMID- 27368174 TI - [Not Available]. PMID- 27368176 TI - [Not Available]. PMID- 27368177 TI - [Not Available]. PMID- 27368178 TI - [Not Available]. PMID- 27368179 TI - [Not Available]. PMID- 27368180 TI - [Not Available]. PMID- 27368181 TI - [Not Available]. PMID- 27368182 TI - [Not Available]. PMID- 27368183 TI - Three-dimensional architectures of P2X2-/P2X3-immunoreactive afferent nerve terminals in the rat carotid body as revealed by confocal laser scanning microscopy. AB - We investigated the three-dimensional architectures of P2X2-/P2X3-immunoreactive nerve terminals in the rat carotid body using immunohistochemistry with confocal laser microscopy. Nerve endings immunoreactive for P2X2 and P2X3 were associated with clusters of type I cells, whereas some nerve endings were sparsely distributed in a few clusters. Most nerve endings surrounding type I cells were hederiform in shape and extended several flattened axon terminals, which were polygonal or pleomorphic in shape and contained P2X2-/P2X3-immunoreactive products. Three-dimensional reconstruction views revealed that some flattened nerve endings with P2X3 immunoreactivity formed arborized, sac- or goblet-like terminal structures and were attached to type I cells immunoreactive for tyrosine hydroxylase (TH). However, P2X3-immunoreactive axon terminals were sparsely distributed in type I cells immunoreactive for dopamine beta-hydroxylase. Multi immunolabeling for P2X2, S100, and TH revealed that P2X2-immunoreactive axon terminals were attached to TH-immunoreactive type I cells on the inside of type II cells with S100 immunoreactivity. These results revealed the detailed morphology of P2X2-/P2X3-immunoreactive nerve terminals and suggest that sensory nerve endings may integrate chemosensory signals from clustered type I cells with their variform nerve terminals. PMID- 27368186 TI - [Not Available]. PMID- 27368184 TI - Automated multiple trajectory planning algorithm for the placement of stereo electroencephalography (SEEG) electrodes in epilepsy treatment. AB - PURPOSE: About one-third of individuals with focal epilepsy continue to have seizures despite optimal medical management. These patients are potentially curable with neurosurgery if the epileptogenic zone (EZ) can be identified and resected. Stereo-electroencephalography (SEEG) to record epileptic activity with intracranial depth electrodes may be required to identify the EZ. Each SEEG electrode trajectory, the path between the entry on the skull and the cerebral target, must be planned carefully to avoid trauma to blood vessels and conflicts between electrodes. In current clinical practice trajectories are determined manually, typically taking 2-3 h per patient (15 min per electrode). Manual planning (MP) aims to achieve an implantation plan with good coverage of the putative EZ, an optimal spatial resolution, and 3D distribution of electrodes. Computer-assisted planning tools can reduce planning time by quantifying trajectory suitability. METHODS: We present an automated multiple trajectory planning (MTP) algorithm to compute implantation plans. MTP uses dynamic programming to determine a set of plans. From this set a depth-first search algorithm finds a suitable plan. We compared our MTP algorithm to (a) MP and (b) an automated single trajectory planning (STP) algorithm on 18 patient plans containing 165 electrodes. RESULTS: MTP changed all 165 trajectories compared to MP. Changes resulted in lower risk (122), increased grey matter sampling (99), shorter length (92), and surgically preferred entry angles (113). MTP changed 42 % (69/165) trajectories compared to STP. Every plan had between 1 to 8 (median 3.5) trajectories changed to resolve electrode conflicts, resulting in surgically preferred plans. CONCLUSION: MTP is computationally efficient, determining implantation plans containing 7-12 electrodes within 1 min, compared to 2-3 h for MP. PMID- 27368185 TI - Ensemble average propagator-based detection of microstructural alterations after stroke. AB - PURPOSE: New analytical reconstruction techniques of diffusion weighted signal have been proposed. A previous work evidenced the exploitability of some indices derived from the simple harmonic oscillator-based reconstruction and estimation (3D-SHORE) model as numerical biomarkers of neural plasticity after stroke. Here, the analysis is extended to two additional indices: return to the plane/origin (RTPP/RTOP) probabilities. Moreover, several motor networks were introduced and the results were analyzed at different time scales. METHODS: Ten patients underwent three diffusion spectrum imaging (DSI) scans [1 week (tp1), 1 month (tp2) and 6 months (tp3) after stroke]. Ten matched controls underwent two DSI scans 1 month apart. 3D-SHORE was used for reconstructing the signal and the microstructural indices were derived. Tract-based analysis was performed along motor cortical, subcortical and transcallosal networks in the contralesional area. RESULTS: The optimal intra-class correlation coefficient (ICC) was obtained in the subcortical loop for propagator anisotropy (ICC [Formula: see text] 0.96), followed by generalized fractional anisotropy (ICC [Formula: see text] 0.94). The new indices reached the highest stability in the transcallosal network and performed well in the cortical and subcortical networks with the exception of RTOP in the cortical loop (ICC [Formula: see text] 0.59). They allowed discriminating patients from controls at the majority of the timescales. Finally, the regression model using indices calculated along the subcortical loop at tp1 resulted in the best prediction of clinical outcome. CONCLUSIONS: The whole set of microstructural indices provide measurements featuring high precision. The new indices allow discriminating patients from controls in all networks, except for RTPP in the cortical loop. Moreover, the 3D-SHORE indices in subcortical connections constitute a good regression model for predicting the clinical outcome at 6 months, supporting their suitability as numerical biomarkers for neuronal plasticity after stroke. PMID- 27368188 TI - [Not Available]. PMID- 27368187 TI - [Not Available]. PMID- 27368189 TI - [Not Available]. PMID- 27368190 TI - [Not Available]. PMID- 27368191 TI - [Not Available]. PMID- 27368192 TI - [Not Available]. PMID- 27368193 TI - [Not Available]. PMID- 27368194 TI - [Not Available]. PMID- 27368195 TI - Engineers' Responsibilities for Global Electronic Waste: Exploring Engineering Student Writing Through a Care Ethics Lens. AB - This paper provides an empirically informed perspective on the notion of responsibility using an ethical framework that has received little attention in the engineering-related literature to date: ethics of care. In this work, we ground conceptual explorations of engineering responsibility in empirical findings from engineering student's writing on the human health and environmental impacts of "backyard" electronic waste recycling/disposal. Our findings, from a purposefully diverse sample of engineering students in an introductory electrical engineering course, indicate that most of these engineers of tomorrow associated engineers with responsibility for the electronic waste (e-waste) problem in some way. However, a number of responses suggested attempts to deflect responsibility away from engineers towards, for example, the government or the companies for whom engineers work. Still other students associated both engineers and non engineers with responsibility, demonstrating the distributed/collective nature of responsibility that will be required to achieve a solution to the global problem of excessive e-waste. Building upon one element of a framework for care ethics adopted from the wider literature, these empirical findings are used to facilitate a preliminary, conceptual exploration of care-ethical responsibility within the context of engineering and e-waste recycling/disposal. The objective of this exploration is to provide a first step toward understanding how care ethical responsibility applies to engineering. We also hope to seed dialogue within the engineering community about its ethical responsibilities on the issue. We conclude the paper with a discussion of its implications for engineering education and engineering ethics that suggests changes for educational policy and the practice of engineering. PMID- 27368197 TI - [Not Available]. PMID- 27368199 TI - [Not Available]. PMID- 27368198 TI - [Not Available]. PMID- 27368196 TI - Extra-renal locations of the a4 subunit of H(+)ATPase. AB - BACKGROUND: Vacuolar-type proton pumps help maintain acid-base homeostasis either within intracellular compartments or at specialised plasma membranes. In mammals they are made up of 13 subunits, which form two functional domains. A number of the subunits have variants that display tissue restricted expression patterns such that in specialised cell types they replace the generic subunits at some sub cellular locations. The tissue restricted a4 subunit has previously been reported at the plasma membrane in the kidney, inner ear, olfactory epithelium and male reproductive tract. RESULTS: In this study novel locations of the a4 subunit were investigated using an Atp6v0a4 knockout mouse line in which a LacZ reporter cassette replaced part of the gene. The presence of a4 in the olfactory epithelium was further investigated and the additional presence of C2 and d2 subunits identified. The a4 subunit was found in the uterus of pregnant animals and a4 was identified along with d2 and C2 in the embryonic visceral yolk sac. In the male reproductive tract a4 was seen in the novel locations of the prostatic alveoli and the ampullary glands as well as the previously reported epididymis and vas deferens. CONCLUSIONS: The identification of novel locations for the a4 subunit and other tissue-restricted subunits increases the range of unique subunit combinations making up the proton pump. These studies suggest additional roles of the proton pump, indicating a further range of homologue-specific functions for tissue-restricted subunits. PMID- 27368200 TI - [Not Available]. PMID- 27368201 TI - [Not Available]. PMID- 27368202 TI - [Not Available]. PMID- 27368203 TI - [Not Available]. PMID- 27368204 TI - [Not Available]. PMID- 27368205 TI - [Not Available]. PMID- 27368206 TI - [Not Available]. PMID- 27368207 TI - [Not Available]. PMID- 27368208 TI - [Not Available]. PMID- 27368210 TI - [Not Available]. PMID- 27368209 TI - [Not Available]. PMID- 27368211 TI - [Not Available]. PMID- 27368212 TI - [Not Available]. PMID- 27368214 TI - [Not Available]. PMID- 27368213 TI - [Not Available]. PMID- 27368215 TI - [Not Available]. PMID- 27368216 TI - [Not Available]. PMID- 27368217 TI - [Not Available]. PMID- 27368218 TI - [Not Available]. PMID- 27368219 TI - [Not Available]. PMID- 27368220 TI - [Not Available]. PMID- 27368221 TI - [Not Available]. PMID- 27368222 TI - [Not Available]. PMID- 27368223 TI - [Not Available]. PMID- 27368224 TI - [Not Available]. PMID- 27368225 TI - [Not Available]. PMID- 27368226 TI - [Not Available]. PMID- 27368227 TI - [Not Available]. PMID- 27368228 TI - [Not Available]. PMID- 27368229 TI - [Not Available]. PMID- 27368230 TI - [Not Available]. PMID- 27368231 TI - [Not Available]. PMID- 27368232 TI - Antibacterial Activity of Hibicuslide C on Multidrug-Resistant Pseudomonas aeruginosa Isolates. AB - Pseudomonas aeruginosa is a gram-negative bacterium that is frequently related to natural resistance to many drugs. In this work, the inhibition of growth against P. aeruginosa and multidrug-resistant P. aeruginosa (MDRPA) isolated from patients at Kyungpook National University was confirmed for hibicuslide C, essential oil components from Abutilon theophrasti. Hibicuslide C has antifungal activity with membrane disruption and apoptotic response against Candida albicans. However, its antibacterial activity was not reported yet. Cells treated with hibicuslide C was showed that its antipseudomonal activity is related to gDNA fragmentation and damage by TUNEL and gDNA electrophoresis. Furthermore, hibicuslide C worked synergistically with fluoroquinolones and rifampicin against MDRPA regardless of the ATP-associated mechanism. The antibiofilm activity possessed sole-resulting tissue culture plate method; besides that, the antibiofilm activity of other antibiotics was supported in particular MDRPA. The essential oil components like hibicuslide C may have antipseudomonal activity and, furthermore, increase in bacterial antibiotic susceptibility. PMID- 27368234 TI - Backbone resonance assignments for the SET domain of the human methyltransferase NSD2. AB - Aberrant NSD2 methyltransferase activity is implicated as the oncogenic driver in multiple myeloma, suggesting opportunities for novel therapeutic intervention. The methyltransferase activity of NSD2 resides in its catalytic SET domain, which is conserved among most lysine methyltransferases. Here we report the backbone [Formula: see text], N, C[Formula: see text], [Formula: see text] and side-chain [Formula: see text] assignments of a 25 kDa NSD2 SET domain construct, spanning residues 991-1203. A chemical shift analysis of C[Formula: see text], [Formula: see text] and [Formula: see text] resonances predicts a secondary structural pattern that is in agreement with homology models. PMID- 27368233 TI - Pre-deployment Year Mental Health Diagnoses and Treatment in Deployed Army Women. AB - We estimated the prevalence of select mental health diagnoses (MHDX) and mental health treatment (MHT), and identified characteristics associated with MHT during the pre-deployment year (365 days before deployment) in active duty Army women (N = 14,633) who returned from Iraq or Afghanistan deployments in FY2010. Pre deployment year prevalence estimates were: 26.2 % for any select MHDX and 18.1 % for any MHT. Army women who had physical injuries since FY2002 or any behavioral health treatment between FY2002 and the pre-deployment year had increased odds of pre-deployment year MHT. During the pre-deployment year, a substantial percentage of Army women had MHDX and at least one MHT encounter or stay. Future research should determine if pre-deployment MHDX among Army women reflect vulnerability to future MHDX, or if pre-deployment MHT results in protection from chronic symptoms. PMID- 27368236 TI - [Not Available]. PMID- 27368235 TI - People, planet and participation: the Kuching statement on healthy, just and sustainable urban development. AB - This statement was commissioned by the UNU International Institute for Global Health in the run up to Habitat III-the third United Nations conference on housing and sustainable urban development. The statement draws on insights from the World Urban Campaign thinkers campus held during 24-27 January 2016 in Kuching, a WHO-designated healthy city. PMID- 27368237 TI - [Not Available]. PMID- 27368238 TI - [Not Available]. PMID- 27368239 TI - [Not Available]. PMID- 27368240 TI - [Not Available]. PMID- 27368241 TI - [Not Available]. PMID- 27368242 TI - [Not Available]. PMID- 27368243 TI - [Not Available]. PMID- 27368244 TI - [Not Available]. PMID- 27368245 TI - [Not Available]. PMID- 27368246 TI - [Not Available]. PMID- 27368247 TI - [Not Available]. PMID- 27368248 TI - [Not Available]. PMID- 27368249 TI - [Not Available]. PMID- 27368250 TI - [Not Available]. PMID- 27368251 TI - [Not Available]. PMID- 27368253 TI - [Not Available]. PMID- 27368252 TI - [Not Available]. PMID- 27368254 TI - [Not Available]. PMID- 27368255 TI - [Not Available]. PMID- 27368256 TI - [Not Available]. PMID- 27368257 TI - Randomized trial of technology-assisted self-monitoring of blood glucose by low income seniors: improved glycemic control in type 2 diabetes mellitus. AB - Self-monitoring of blood glucose (SMBG) has been recommended for people with type 2 diabetes mellitus. This trial tested an automated self-management monitor (ASMM) that reminds patients to perform SMBG, provides feedback on results of SMBG, and action tips for improved self-management. This delayed-start trial randomized participants to using the ASMM immediately (IG), or following a delay of 6 months (DG). Glycated hemoglobin (HgbA1c) level and survey data was collected at home visits every 3 months. 44 diabetic men and women, mean age 70, completed the 12-month trial. Baseline HgbA1c was 8.1 % +/- 1.0, dropping to 7.3 +/- 1.0 by 9 months, with a 3-month lag in the DG (F = 3.56, p = 0.004). Decrease in HgbA1c was significantly correlated to increased frequency of SMBG, R = 0.588, p < 0.01. Providing older diabetics with objective immediate contingent feedback resulted in more frequent SMBG that correlated with better glycemic control. This type of technology may provide real-time feedback not only to patient users, but to the health care system, allowing better integration of provider recommendations with patient-centered action. PMID- 27368258 TI - [Not Available]. PMID- 27368259 TI - [Not Available]. PMID- 27368260 TI - [Not Available]. PMID- 27368261 TI - [Not Available]. PMID- 27368262 TI - [Not Available]. PMID- 27368263 TI - [Not Available]. PMID- 27368265 TI - [Not Available]. PMID- 27368264 TI - [Not Available]. PMID- 27368266 TI - [Not Available]. PMID- 27368267 TI - [Not Available]. PMID- 27368268 TI - [Not Available]. PMID- 27368269 TI - [Not Available]. PMID- 27368270 TI - [Not Available]. PMID- 27368271 TI - [Not Available]. PMID- 27368272 TI - [Not Available]. PMID- 27368273 TI - [Not Available]. PMID- 27368274 TI - [Not Available]. PMID- 27368275 TI - [Not Available]. PMID- 27368276 TI - [Not Available]. PMID- 27368277 TI - [Not Available]. PMID- 27368278 TI - Three-dimensional simulation of pancreatic surgery showing the size and location of the main pancreatic duct. AB - PURPOSE: We performed three-dimensional (3D) surgical simulation of pancreatic surgery, including the size and location of the main pancreatic duct on the resected pancreatic surface. METHODS: The subjects of this retrospective analysis were 162 patients who underwent pancreatic surgery. This cohort was sequentially divided into a "without-3D" group (n = 81) and a "with-3D" group (n = 81). We compared the pancreatic duct diameter and its location, using nine sections in a grid pattern, with the intraoperative findings. The perioperative outcomes were also compared between patients who underwent pancreaticoduodenectomy (PD) and those who underwent distal pancreatectomy (DP). RESULTS: There were no significant differences in the main pancreatic duct diameter between the 3D simulated values and the operative findings. The 3D-simulated main pancreatic duct location was consistent with its actual location in 80 % of patients (65/81). In comparing the PD and DP groups, the intraoperative blood loss was 1174 +/- 867 and 817 +/- 925 ml in the without-3D group, and 828 +/- 739 and 307 +/- 192 ml in the with-3D group, respectively (p = 0.024, 0.026). CONCLUSION: The 3D surgical simulation provided useful information to promote our understanding of the pancreatic anatomy, including details on the size and location of the main pancreatic duct. PMID- 27368281 TI - [Not Available]. PMID- 27368280 TI - [Not Available]. PMID- 27368282 TI - [Not Available]. PMID- 27368279 TI - Effects of dexmedetomidine and propofol on patient-ventilator interaction in difficult-to-wean, mechanically ventilated patients: a prospective, open-label, randomised, multicentre study. AB - BACKGROUND: Dexmedetomidine can be used for sedation of mechanically ventilated patients and has minor respiratory effects. The aim of this study was to compare the incidence of patient-ventilator dyssynchronies during sedation with dexmedetomidine or propofol. METHODS: We conducted a multicentre, prospective, open-label, randomised clinical trial, comparing dexmedetomidine with standard propofol sedation at three intensive care units of university hospitals in Italy. Twenty difficult-to-wean patients for whom the first weaning trial had failed and who were on pressure support ventilation were randomised to receive sedation with either dexmedetomidine or propofol at a similar level of sedation (Richmond Agitation-Sedation Scale [RASS] score +1 to -2). The asynchrony index (AI) was calculated using tracings of airflow, airway pressure and electrical activity of the diaphragm sampled at 0, 0.5, 1, 2, 6, 12, 18 and 24 h. RESULTS: The mean AI was lower with dexmedetomidine than with propofol from 2 h onwards, although the two groups significantly differed only at 12 h (2.68 % vs 9.10 %, p < 0.05). No further difference was observed at 18 and 24 h. CONCLUSIONS: When sedation with propofol and dexmedetomidine was compared at similar RASS scores of patients in whom first weaning trial had failed, the AI was lower with dexmedetomidine than with propofol, and this difference was statistically significant at 12 h. These results suggest that sedation with dexmedetomidine may offer some advantages in terms of patient-ventilator synchrony. PMID- 27368283 TI - [Not Available]. PMID- 27368284 TI - [Not Available]. PMID- 27368285 TI - [Not Available]. PMID- 27368286 TI - [Not Available]. PMID- 27368287 TI - [Not Available]. PMID- 27368288 TI - [Not Available]. PMID- 27368289 TI - [Not Available]. PMID- 27368290 TI - [Not Available]. PMID- 27368291 TI - [Not Available]. PMID- 27368292 TI - [Not Available]. PMID- 27368293 TI - [Not Available]. PMID- 27368294 TI - [Not Available]. PMID- 27368296 TI - [Not Available]. PMID- 27368297 TI - [Not Available]. PMID- 27368298 TI - [Not Available]. PMID- 27368299 TI - [Not Available]. PMID- 27368300 TI - [Not Available]. PMID- 27368301 TI - [Not Available]. PMID- 27368295 TI - Epigenetic changes in T-cell and monocyte signatures and production of neurotoxic cytokines in ALS patients. AB - We have investigated transcriptional and epigenetic differences in peripheral blood mononuclear cells (PBMCs) of monozygotic female twins discordant in the diagnosis of amyotrophic lateral sclerosis (ALS). Exploring DNA methylation differences by reduced representation bisulfite sequencing (RRBS), we determined that, over time, the ALS twin developed higher abundances of the CD14 macrophages and lower abundances of T cells compared to the non-ALS twin. Higher macrophage signature in the ALS twin was also shown by RNA sequencing (RNA-seq). Moreover, the twins differed in the methylome at loci near several genes, including EGFR and TNFRSF11A, and in the pathways related to the tretinoin and H3K27me3 markers. We also tested cytokine production by PBMCs. The ALS twin's PBMCs spontaneously produced IL-6 and TNF-alpha, whereas PBMCs of the healthy twin produced these cytokines only when stimulated by superoxide dismutase (SOD)-1. These results and flow cytometric detection of CD45 and CD127 suggest the presence of memory T cells in both twins, but effector T cells only in the ALS twin. The ALS twin's PBMC supernatants, but not the healthy twin's, were toxic to rat cortical neurons, and this toxicity was strongly inhibited by an IL-6 receptor antibody (tocilizumab) and less well by TNF-alpha and IL-1beta antibodies. The putative neurotoxicity of IL-6 and TNF-alpha is in agreement with a high expression of these cytokines on infiltrating macrophages in the ALS spinal cord. We hypothesize that higher macrophage abundance and increased neurotoxic cytokines have a fundamental role in the phenotype and treatment of certain individuals with ALS.-Lam, L., Chin, L., Halder, R. C., Sagong, B., Famenini, S., Sayre, J., Montoya, D., Rubbi L., Pellegrini, M., Fiala, M. Epigenetic changes in T-cell and monocyte signatures and production of neurotoxic cytokines in ALS patients. PMID- 27368302 TI - [Not Available]. PMID- 27368303 TI - [Not Available]. PMID- 27368304 TI - [Not Available]. PMID- 27368305 TI - [Not Available]. PMID- 27368306 TI - [Not Available]. PMID- 27368307 TI - [Not Available]. PMID- 27368308 TI - [Not Available]. PMID- 27368309 TI - [Not Available]. PMID- 27368310 TI - CD27 natural killer cell subsets play different roles during the pre-onset stage of experimental autoimmune encephalomyelitis. AB - NK cells participate in the development of human multiple sclerosis (MS) and mouse experimental autoimmune encephalomyelitis (EAE), but the roles of different NK cell subsets in disease onset remain poorly understood. In this study, murine NK cells were divided into CD27(high) and CD27(low/-) subsets. The CD27(high) subset was decreased and the CD27(low/-) subset was increased in lymphoid organs during the pre-onset stage of EAE. Compared with the counterpart in naive mice, the CD27(high) subset showed lower expression of Ly49D, Ly49H and NKG2D, and less production of IFN-gamma, whereas the CD27(low/-) subset showed similar expression of the above mentioned surface receptors but higher cytotoxic activity in EAE mice. Compared with the CD27(high) subset, the CD27(low/-) subset exhibited increased promotion of DC maturation and no significant inhibition of T cells proliferation and Th17 cells differentiation in vitro Additionally, adoptive transfer of the CD27(low/-) subset, but not the CD27(high) subset, exacerbated the severity of EAE. Collectively, our data suggest the CD27 NK cell subsets play different roles in controlling EAE onset, which provide a new understanding for the regulation of NK cell subsets in early autoimmune disease. PMID- 27368312 TI - [Not Available]. PMID- 27368311 TI - Developing a Framework for Evaluating Ethical Outcomes of Good Participatory Practices in TB Clinical Drug Trials. AB - Good Participatory Practice Guidelines for TB Drug Trials (GPP-TB) were issued in 2012, based on similar guidelines for HIV prevention and reflecting growing acceptance of the importance of community engagement and participatory strategies in clinical research. Though the need for such strategies is clear, evaluation of the benefits and burdens are needed. Working with a diverse group of global TB stakeholders including advocates, scientists, and ethicists, we used a Theory of Change approach to develop an evaluation framework for GPP-TB that includes a clearly defined ethical goal, a set of powerful strategies derived from GPP-TB practices for achieving the goal, and outcomes connecting strategies to goal. The framework is a first step in systematically evaluating participatory research in clinical trials. PMID- 27368314 TI - [Not Available]. PMID- 27368313 TI - [Not Available]. PMID- 27368315 TI - [Not Available]. PMID- 27368316 TI - [Not Available]. PMID- 27368318 TI - [Not Available]. PMID- 27368317 TI - [Not Available]. PMID- 27368319 TI - [Not Available]. PMID- 27368321 TI - [Not Available]. PMID- 27368320 TI - [Not Available]. PMID- 27368322 TI - [Not Available]. PMID- 27368323 TI - [Not Available]. PMID- 27368324 TI - [Not Available]. PMID- 27368325 TI - [Not Available]. PMID- 27368326 TI - [Not Available]. PMID- 27368327 TI - [Not Available]. PMID- 27368328 TI - [Not Available]. PMID- 27368329 TI - [Not Available]. PMID- 27368330 TI - [Not Available]. PMID- 27368331 TI - [Not Available]. PMID- 27368332 TI - [Not Available]. PMID- 27368333 TI - [Not Available]. PMID- 27368334 TI - [Not Available]. PMID- 27368335 TI - A new risk factor for head and neck squamous cell carcinoma: human papillomavirus. PMID- 27368336 TI - Incidence and risk factors of synchronous colorectal cancer in patients with esophageal cancer: an analysis of 480 consecutive colonoscopies before surgery. AB - BACKGROUND: The precise incidence rates of multiple primary colorectal cancers in esophageal cancer patients are unknown. METHODS: In total, 480 consecutive patients with esophageal cancers surgically resected in the Kumamoto University Hospital received preoperative total colonoscopy for the assessment of colorectal disease between April 2005 and February 2016. We retrospectively investigated the occurrence of synchronous colorectal cancer with esophageal cancer. In addition, we examined the risk factors for the incidence of multiple primary colorectal cancers. RESULTS: Of the 480 patients, 14 (2.9 %) had synchronous colorectal cancers, 13 had well-differentiated tubular adenocarcinomas, and 1 had papillary adenocarcinoma. Other 14 patients had metachronous colorectal cancer. The current incidence rates of synchronous and total (both synchronous and metachronous) colorectal cancers outnumbered those in normal healthy population and those in esophageal cancer patients which previously reported by The Japan Esophageal Society. The age >=70 years (hazard ratio 4.82, 95 % confidence interval 1.473 15.78; p = 0.009) and Brinkman index >=800 (hazard ratio 3.47, 95 % confidence interval 1.056-11.37; p = 0.040) were the independent risk factors for the incidence of synchronous colorectal cancer. They were also the independent risk factors for the incidence of total colorectal cancer. CONCLUSIONS: The results of the present study suggested that pretreatment screening with total colonoscopy is meaningful for patients with esophageal cancer, because the frequency of synchronous colorectal cancer was not negligible. Particularly, in patients >70 years and with history of heavy smoking, pretreatment colonoscopy might be necessary. PMID- 27368337 TI - Donor interleukin 6 gene polymorphisms predict the recurrence of hepatocellular carcinoma after liver transplantation. AB - BACKGROUND: Application of the Milan criteria is an effective strategy to select patients with hepatocellular carcinoma (HCC) for liver transplantation, but HCC recurrence is still a major concern. The aim of this study was to determine whether interleukin 6 (IL6) polymorphisms and clinical variables are potential predictors for HCC recurrence and prognosis after transplantation. METHODS: A total of 110 consecutive patients with HCC undergoing liver transplantation were enrolled in the study. Six tag single nucleotide polymorphisms in IL6 were genotyped in both the donors and recipients. Demographic characteristics, HCC features, and IL6 polymorphisms were assessed against HCC recurrence. RESULTS: Pretransplant hepatitis B virus DNA (P = 0.014), pretransplant serum alpha fetoprotein (P = 0.035), number of nodules (P = 0.011), diameter of main nodule (P = 0.001), macrovascular invasion (P = 0.001), microvascular invasion (P = 0.001), HCC exceeding the Milan criteria (P < 0.001), and donor rs2069852 AA genotype (P = 0.010) were associated with HCC recurrence. Recurrence-free survival rate and overall survival rate were significantly lower (P = 0.011 and P = 0.026, respectively) in patients whose donor had the rs2069852 AA genotype than in those whose donor had the AG and GG genotypes. Independent risk factors for recurrence-free survival and overall survival were microvascular invasion (P = 0.003; P = 0.002), HCC exceeding the Milan criteria (P < 0.001; P = 0.001), and donor rs2069852 AA genotype (P = 0.002; P = 0.010). CONCLUSIONS: Our data suggest that donor IL6 rs2069852 polymorphisms may be a potential genetic marker for HCC recurrence after liver transplantation in the Han Chinese population. PMID- 27368339 TI - The Never-Ending Public Health Issue of Adulterants in Abused Drugs. PMID- 27368338 TI - Identity by descent fine mapping of familial adult myoclonus epilepsy (FAME) to 2p11.2-2q11.2. AB - Familial adult myoclonus epilepsy (FAME) is a rare autosomal dominant disorder characterized by adult onset, involuntary muscle jerks, cortical myoclonus and occasional seizures. FAME is genetically heterogeneous with more than 70 families reported worldwide and five potential disease loci. The efforts to identify potential causal variants have been unsuccessful in all but three families. To date, linkage analysis has been the main approach to find and narrow FAME critical regions. We propose an alternative method, pedigree free identity-by descent (IBD) mapping, that infers regions of the genome between individuals that have been inherited from a common ancestor. IBD mapping provides an alternative to linkage analysis in the presence of allelic and locus heterogeneity by detecting clusters of individuals who share a common allele. Succeeding IBD mapping, gene prioritization based on gene co-expression analysis can be used to identify the most promising candidate genes. We performed an IBD analysis using high-density single nucleotide polymorphism (SNP) array data followed by gene prioritization on a FAME cohort of ten European families and one Australian/New Zealander family; eight of which had known disease loci. By identifying IBD regions common to multiple families, we were able to narrow the FAME2 locus to a 9.78 megabase interval within 2p11.2-q11.2. We provide additional evidence of a founder effect in four Italian families and allelic heterogeneity with at least four distinct founders responsible for FAME at the FAME2 locus. In addition, we suggest candidate disease genes using gene prioritization based on gene co expression analysis. PMID- 27368342 TI - Utilization of Photochemically Induced Fluorescence Detection for HPLC Determination of Genotoxic Impurities in the Vortioxetine Manufacturing Process. AB - An analytical reversed-phase high-performance liquid chromatography (HPLC) method for the detection and quantitative determination of two genotoxic impurities at ppm level present in the vortioxetine manufacturing process is described. Applying the concept of threshold of toxicological concern, a limit of 75 ppm each for both genotoxic impurities was calculated based on the maximum daily dose of active pharmaceutical ingredients. The novel reversed-phase HPLC method with photochemically induced fluorescence detection was developed on XSELECT Charged Surface Hybrid Phenyl-Hexyl column using the mobile phase consisted a mixture of 10 mM ammonium formate pH 3.0 and acetonitrile. The elution was performed using an isocratic composition of 48:52 (v/v) at a flow rate of 1.0 mL/min. The photochemically induced fluorescence detection is based on the use of UV irradiation at 254 nm through measuring the fluorescence intensity at 300 nm and an excitation wavelength of 272 nm to produce fluorescent derivatives of both genotoxic impurities. The online photochemical conversion and detection is easily accomplished for two expected genotoxic impurities and provides a sufficiently low limit detection and quantification for the target analysis. PMID- 27368340 TI - A protein map of the yeast activated spliceosome as obtained by electron microscopy. AB - We have elucidated the spatial arrangement of proteins and snRNP subunits within the purified spliceosomal B(act) complex from Saccharomyces cerevisiae, using negative-stain immunoelectron microscopy. The B(act) spliceosome exhibits a mushroom-like shape with a main body connected to a foot and a steep and a shallow slope. The U5 core components, including proteins Snu114 and Prp8, are located in the main body and foot, while Brr2 is on the shallow slope. U2 snRNP components and the RNA helicase Prp2 were predominantly located in the upper regions of both slopes. While several proteins of the "nineteen complex" are located on the steep slope, Prp19, Cef1, and the U6 snRNA-binding protein Cwc2 are on the main body. Our results also indicate that the catalytic core RNP of the spliceosome resides in its main body. We thus assign distinct domains of the B(act) complex to its snRNP and protein components, and we provide first structural insights into the remodeling events at the spliceosome during its transformation from the B to the B(act) complex. PMID- 27368343 TI - Validated UPLC and TLC-Densitometry Stability Indicating Methods for the Determination of Rafoxanide in the Presence of Its Degradation Products. AB - Two sensitive and accurate stability-indicating chromatographic methods were developed and validated for the determination of rafoxanide (RFX). Degradation products were identified by mass spectrometry and IR spectroscopy. The first is ultra-performance liquid chromatography method where separation was performed using acetonitrile:0.005 M potassium dihydrogen orthophosphate (pH 3.5) in a ratio of 80:20 by volume as a mobile phase using a Hypersil GOLDTM C8 column 1.9 mm (50 * 2.1 mm), UV detection was adjusted at 220 nm and the flow rate was 0.6 mL min-1 The other is a thin-layer chromatography-densitometry method where separation was achieved using a mobile phase composed of chloroform:ethyl acetate:toluene:ammonia (5:4:3:0.1 by volume) on silica gel 60 F254 plates, and densitometric detection was done at 280 nm. Validation was achieved as per the ICH guidelines. The proposed methods proved to be accurate, robust, specific and suitable for application as stability-indicating methods for routine analysis of RFX in quality control laboratories. PMID- 27368341 TI - A general method for rapid and cost-efficient large-scale production of 5' capped RNA. AB - The eukaryotic mRNA 5' cap structure is indispensible for pre-mRNA processing, mRNA export, translation initiation, and mRNA stability. Despite this importance, structural and biophysical studies that involve capped RNA are challenging and rare due to the lack of a general method to prepare mRNA in sufficient quantities. Here, we show that the vaccinia capping enzyme can be used to produce capped RNA in the amounts that are required for large-scale structural studies. We have therefore designed an efficient expression and purification protocol for the vaccinia capping enzyme. Using this approach, the reaction scale can be increased in a cost-efficient manner, where the yields of the capped RNA solely depend on the amount of available uncapped RNA target. Using a large number of RNA substrates, we show that the efficiency of the capping reaction is largely independent of the sequence, length, and secondary structure of the RNA, which makes our approach generally applicable. We demonstrate that the capped RNA can be directly used for quantitative biophysical studies, including fluorescence anisotropy and high-resolution NMR spectroscopy. In combination with (13)C-methyl labeled S-adenosyl methionine, the methyl groups in the RNA can be labeled for methyl TROSY NMR spectroscopy. Finally, we show that our approach can produce both cap-0 and cap-1 RNA in high amounts. In summary, we here introduce a general and straightforward method that opens new means for structural and functional studies of proteins and enzymes in complex with capped RNA. PMID- 27368344 TI - Understanding Past Population Dynamics: Bayesian Coalescent-Based Modeling with Covariates. AB - Effective population size characterizes the genetic variability in a population and is a parameter of paramount importance in population genetics and evolutionary biology. Kingman's coalescent process enables inference of past population dynamics directly from molecular sequence data, and researchers have developed a number of flexible coalescent-based models for Bayesian nonparametric estimation of the effective population size as a function of time. Major goals of demographic reconstruction include identifying driving factors of effective population size, and understanding the association between the effective population size and such factors. Building upon Bayesian nonparametric coalescent based approaches, we introduce a flexible framework that incorporates time varying covariates that exploit Gaussian Markov random fields to achieve temporal smoothing of effective population size trajectories. To approximate the posterior distribution, we adapt efficient Markov chain Monte Carlo algorithms designed for highly structured Gaussian models. Incorporating covariates into the demographic inference framework enables the modeling of associations between the effective population size and covariates while accounting for uncertainty in population histories. Furthermore, it can lead to more precise estimates of population dynamics. We apply our model to four examples. We reconstruct the demographic history of raccoon rabies in North America and find a significant association with the spatiotemporal spread of the outbreak. Next, we examine the effective population size trajectory of the DENV-4 virus in Puerto Rico along with viral isolate count data and find similar cyclic patterns. We compare the population history of the HIV-1 CRF02_AG clade in Cameroon with HIV incidence and prevalence data and find that the effective population size is more reflective of incidence rate. Finally, we explore the hypothesis that the population dynamics of musk ox during the Late Quaternary period were related to climate change. [Coalescent; effective population size; Gaussian Markov random fields; phylodynamics; phylogenetics; population genetics. PMID- 27368346 TI - Mislocated FUS is sufficient for gain-of-toxic-function amyotrophic lateral sclerosis phenotypes in mice. AB - Mutations in RNA-binding proteins, including fused in sarcoma (FUS) and TAR DNA binding protein 43 (TDP-43, encoded by TARDBP), are associated with sporadic and familial amyotrophic lateral sclerosis. A major question is whether neuronal loss is caused by toxic gain-of-function cytoplasmic aggregates or loss of nuclear RNA binding protein function. We generated a transgenic mouse overexpressing exogenous FUS without a nuclear localization signal (DeltaNLS-FUS), which developed progressive spastic motor deficits and neuronal loss in the motor cortex. The DeltaNLS-FUS protein was restricted to the cytoplasm and formed ubiquitin/p62-positive aggregates. Endogenous FUS expression, nuclear localization, and splicing activity were not altered, indicating that mislocated FUS is sufficient for proteinopathy. Crossing DeltaNLS-FUS with wild-type human TDP-43 transgenic mice exacerbated pathological and behavioural phenotypes, suggesting that both proteins are involved in a common cascade. RNA-sequence analysis revealed specific transcriptome alterations, including genes regulating dynein-associated molecules and endoplasmic reticulum stress. DeltaNLS-FUS mice are promising tools for understanding amyotrophic lateral sclerosis pathogenesis and testing new therapeutic approaches. PMID- 27368347 TI - Blocking of CD1d Decreases Trypanosoma cruzi-Induced Activation of CD4-CD8- T Cells and Modulates the Inflammatory Response in Patients With Chagas Heart Disease. AB - The control of inflammatory responses to prevent the deadly cardiac pathology in human Chagas disease is a desirable and currently unattained goal. Double negative (DN) T cells are important sources of inflammatory and antiinflammatory cytokines in patients with Chagas heart disease and those with the indeterminate clinical form of Chagas disease, respectively. Given the importance of DN T cells in immunoregulatory processes and their potential as targets for controlling inflammation-induced pathology, we studied the involvement of CD1 molecules in the activation and functional profile of Trypanosoma cruzi-specific DN T cells. We observed that parasite stimulation significantly increased the expression of CD1a, CD1b, CD1c, and CD1d by CD14(+) cells from patients with Chagas disease. Importantly, among the analyzed molecules, only CD1d expression showed an association with the activation of DN T cells, as well as with worse ventricular function in patients with Chagas disease. Blocking of CD1d-mediated antigen presentation led to a clear reduction of DN T-cell activation and a decrease in the expression of interferon gamma (IFN-gamma) by DN T cells. Thus, our results showed that antigen presentation via CD1d is associated with activation of DN T cells in Chagas disease and that CD1d blocking leads to downregulation of IFN gamma by DN T cells from patients with Chagas heart disease, which may be a potential target for preventing progression of inflammation-mediated dilated cardiomyopathy. PMID- 27368345 TI - Anticipation-related brain connectivity in bipolar and unipolar depression: a graph theory approach. AB - Bipolar disorder is often misdiagnosed as major depressive disorder, which leads to inadequate treatment. Depressed individuals versus healthy control subjects, show increased expectation of negative outcomes. Due to increased impulsivity and risk for mania, however, depressed individuals with bipolar disorder may differ from those with major depressive disorder in neural mechanisms underlying anticipation processes. Graph theory methods for neuroimaging data analysis allow the identification of connectivity between multiple brain regions without prior model specification, and may help to identify neurobiological markers differentiating these disorders, thereby facilitating development of better therapeutic interventions. This study aimed to compare brain connectivity among regions involved in win/loss anticipation in depressed individuals with bipolar disorder (BDD) versus depressed individuals with major depressive disorder (MDD) versus healthy control subjects using graph theory methods. The study was conducted at the University of Pittsburgh Medical Center and included 31 BDD, 39 MDD, and 36 healthy control subjects. Participants were scanned while performing a number guessing reward task that included the periods of win and loss anticipation. We first identified the anticipatory network across all 106 participants by contrasting brain activation during all anticipation periods (win anticipation + loss anticipation) versus baseline, and win anticipation versus loss anticipation. Brain connectivity within the identified network was determined using the Independent Multiple sample Greedy Equivalence Search (IMaGES) and Linear non-Gaussian Orientation, Fixed Structure (LOFS) algorithms. Density of connections (the number of connections in the network), path length, and the global connectivity direction ('top-down' versus 'bottom-up') were compared across groups (BDD/MDD/healthy control subjects) and conditions (win/loss anticipation). These analyses showed that loss anticipation was characterized by denser top-down fronto-striatal and fronto-parietal connectivity in healthy control subjects, by bottom-up striatal-frontal connectivity in MDD, and by sparse connectivity lacking fronto-striatal connections in BDD. Win anticipation was characterized by dense connectivity of medial frontal with striatal and lateral frontal cortical regions in BDD, by sparser bottom-up striatum-medial frontal cortex connectivity in MDD, and by sparse connectivity in healthy control subjects. In summary, this is the first study to demonstrate that BDD and MDD with comparable levels of current depression differed from each other and healthy control subjects in density of connections, connectivity path length, and connectivity direction as a function of win or loss anticipation. These findings suggest that different neurobiological mechanisms may underlie aberrant anticipation processes in BDD and MDD, and that distinct therapeutic strategies may be required for these individuals to improve coping strategies during expectation of positive and negative outcomes. PMID- 27368348 TI - Thioredoxins and Methionine Sulfoxide Reductases in the Pathophysiology of Pneumococcal Meningitis. AB - BACKGROUND: Pneumococcal proteins involved in the resistance against oxidative stress are present in all strains and therefore are potential antigens that could be suitable for new therapies and/or vaccines. Their role in the pathogenesis of pneumococcal meningitis has not been addressed. METHODS: We investigated the individual contributions of extracellular thioredoxin lipoproteins (Etrx1 and Etrx2) and the intracellular and extracellular methionine sulfoxide reductases (SpMsrAB1 and SpMsrAB2, respectively) in the progression and outcome of pneumococcal meningitis, using Kaplan-Meier survival curves, bacteriological and histological studies, and measurements of proinflammatory mediators. RESULTS: The absence of Etrx1, Etrx2, or SpMsrAB1 moderately attenuated virulence as compared to the wild-type strain but did not significantly affect bacterial growth in the brain and bloodstream. Loss of function of SpMsrAB2 alone, both Etrx proteins, or both SpMsrAB proteins resulted in a less severe course of infection, with low numbers of animals dying of infection, a lower risk of associated meningeal inflammation, and reduced bacterial densities in the cerebellum, blood, and spleen. CONCLUSIONS: Our data support the importance of the extracellular redox repair system in virulence and its potential as a target for the design of new antimicrobials and vaccine formulations against Streptococcus pneumoniae. PMID- 27368349 TI - Parenting stress as an indirect pathway to mental health concerns among mothers of children with autism spectrum disorder. AB - The link between autism spectrum disorder symptoms and maternal stress has been well established, yet many mothers remain resilient to more severe psychopathology. For the current online study, 111 mothers of a child with autism spectrum disorder completed questionnaires about their child's symptoms, their own stress related to parenting, and any psychopathology symptoms they were experiencing. Autism spectrum disorder symptom severity was positively related to both parenting stress and maternal psychopathology symptoms. Furthermore, parenting stress mediated the relation between autism spectrum disorder symptom severity and maternal psychopathology symptoms. These results provide evidence for a pathway through which psychopathology may develop among mothers of children with autism spectrum disorder and a potential point of intervention for clinicians serving this population. PMID- 27368350 TI - Examining the reinforcing value of stimuli within social and non-social contexts in children with and without high-functioning autism. AB - One of the key diagnostic criteria for autism spectrum disorder includes impairments in social interactions. This study compared the extent to which boys with high-functioning autism and typically developing boys "value" engaging in activities with a parent or alone. Two different assessments that can empirically determine the relative reinforcing value of social and non-social stimuli were employed: paired-choice preference assessments and progressive-ratio schedules. There were no significant differences between boys with high-functioning autism and typically developing boys on either measure. Moreover, there was a strong correspondence in performance across these two measures for participants in each group. These results suggest that the relative reinforcing value of engaging in activities with a primary caregiver is not diminished for children with autism spectrum disorder. PMID- 27368351 TI - Metabolic Syndrome as a Risk Factor for Alzheimer's Disease: Is Abeta a Crucial Factor in Both Pathologies? AB - SIGNIFICANCE: Recently, chronic degenerative diseases have become one of the main health problems worldwide. That is the case of Alzheimer's disease (AD) and metabolic syndrome (MetS), whose expression can be influenced by different risk factors. Recent Advances: In recent decades, it has been widely described that MetS increases the risk of cognitive impairment and dementia. MetS pathogenesis involves several vascular risk factors such as diabetes, dyslipidemia, hypertension, and insulin resistance (I/R). CRITICAL ISSUES: Reported evidence shows that vascular risk factors are associated with AD, particularly in the development of protein aggregation, inflammation, oxidative stress, neuronal dysfunction, and disturbances in signaling pathways, with insulin receptor signaling being a common alteration between MetS and AD. FUTURE DIRECTIONS: Insulin signaling has been involved in tau phosphorylation and amyloid beta (Abeta) metabolism. However, it has also been demonstrated that Abeta oligomers can bind to insulin receptors, triggering their internalization, decreasing neuron responsiveness to insulin, and promoting insulin I/R. Thus, it could be argued that Abeta could be a convergent factor in the development of both pathologies. Antioxid. Redox Signal. 26, 542-560. PMID- 27368353 TI - Prognostic Impact of Stone-Scoring Systems After Percutaneous Nephrolithotomy for Staghorn Calculi: A Single Center's Experience Over 10 Years. AB - INTRODUCTION: To investigate the prognostic factors associated with stone-free rate (SFR) and complications after percutaneous nephrolithotomy (PCNL) for the treatment of staghorn stone and to compare the predictive value and accuracy of three stone-scoring systems for the treatment success of staghorn stone. PATIENTS AND METHODS: We retrospectively reviewed all patients undergoing PCNL at our center from June 2003 to June 2014. On the basis of noncontrast computed tomography (NCCT) scan images, we calculated Guy's score, S.T.O.N.E. nephrolithometry, and Clinical Research Office of the Endourological Society (CROES) nomogram to assess the association with stone-free status and complications. For statistical evaluation, univariate and multivariate logistic regression analyses were used. RESULTS: During the study period, 886 cases had medical records available. Cases who underwent PCNL for the treatment of staghorn calculi accounted for 34.4% (305/886 cases). Preoperative NCCT was performed in 217 cases. The 217 procedures (205 patients, 12 simultaneous bilateral PCNLs) had a mean stone size of 1358.3 +/- 760.7 mm(2), with 111 (51.2%) partial staghorn and 106 (48.8%) complete staghorn stones. The initial and overall SFRs of PCNL were 53.9% and 70.1%, respectively. The overall complication rate was 32.7% (71/217 cases). On a multivariate logistic regression analysis, independent predictors for SFR were number of involved calices, S.T.O.N.E. nephrolithometry, and pre-existent urinary tract infection (UTI) (odds ratios [ORs] = 1.311, 1.933, and 2.340, respectively). Stone burden was an independent risk factor for the development of complications on multivariate analysis (OR = 2.846 and p = 0.001). CONCLUSION: The results of this study show that multiple involved calices, high grades of S.T.O.N.E. nephrolithometry, and pre-existent UTIs were associated with lower SFR after PCNL for staghorn calculi. Stone burden was an independent risk factor for the development of complications. PMID- 27368354 TI - Adolescent Mice Demonstrate a Distinct Pattern of Injury after Repetitive Mild Traumatic Brain Injury. AB - Recently, there has been increasing interest in outcomes after repetitive mild traumatic brain injury (rmTBI) (e.g., sports concussions). Although most of the scientific attention has focused on elite athlete populations, the sequelae of rmTBI in children and young adults have not been well studied. Prior TBI studies have suggested that developmental differences in response to injury, including differences in excitotoxicity and inflammation, could result in differences in functional and histopathological outcomes after injury. The purpose of this study is to compare outcomes in adolescent (5-week-old) versus adult (4-month-old) mice in a clinically relevant model of rmTBI. We hypothesized that functional and histopathological outcomes after rmTBI would differ in developing adolescent brains compared with mature adult brains. Male adolescent and adult (C57Bl/6) mice were subjected to a weight drop model of rmTBI (n = 10-16/group). Loss of consciousness (LOC) after each injury was measured. Functional outcomes were assessed including tests of balance (rotorod), spatial memory (Morris water maze), and impulsivity (elevated plus maze). After behavioral testing, brains were assessed for histopathological outcomes including microglial immunolabeling and N-methyl-d-aspartate (NMDA) receptor subunit expression. Injured adolescent mice had longer LOC than injured adult mice compared with their respective sham controls. Compared with sham mice, adolescent and adult mice subjected to rmTBI had impaired balance, increased impulsivity, and worse spatial memory that persisted up to 3 months after injury, and the effect of injury was worse in adolescent than in adult mice in terms of spatial memory. Three months after injury, adolescent and adult mice demonstrated increased ionized calcium binding adaptor 1 (IbA1) immunolabeling compared with sham controls. Compared with sham controls, NMDA receptor subtype 2B (NR2B) expression in the hippocampus was reduced by ~20% in both adolescent and adult injured mice. The data suggest that injured adolescent mice may show a distinct pattern of functional deficits after injury that warrants further mechanistic studies. PMID- 27368355 TI - FtsZ Protofilament Curvature Is the Opposite of Tubulin Rings. AB - FtsZ protofilaments (pfs) form the bacterial cytokinetic Z ring. Previous work suggested that a conformational change from straight to curved pfs generated the constriction force. In the simplest model, the C-terminal membrane tether is on the outside of the curved pf, facing the membrane. Tubulin, a homologue of FtsZ, also forms pfs with a curved conformation. However, it is well-established that tubulin rings have the C terminus on the inside of the ring. Could FtsZ and tubulin rings have the opposite curvature? In this study, we explored the FtsZ curvature direction by fusing large protein tags to the FtsZ termini. Thin section electron microscopy showed that the C-terminal tag was on the outside, consistent with the bending pf model. This has interesting implications for the evolution of tubulin. Tubulin likely began with the curvature of FtsZ, but evolution managed to reverse direction to produce outward-curving rings, which are useful for pulling chromosomes. PMID- 27368356 TI - Female Service Members and Symptom Reporting after Combat and Non-Combat-Related Mild Traumatic Brain Injury. AB - Females are often excluded from military-related mild traumatic brain injury (mTBI) research because of its relatively low prevalence in this population. The purpose of this study was to focus on outcome from mTBI in female service members, compared with males. Participants were 172 United States military service members selected from a larger sample that had sustained an mTBI, and were evaluated within 24 months of injury (Age: mean = 28.9, SD = 8.1) at one of six military medical centers. Eighty-six women were matched to 86 men on nine key variables: TBI severity, mechanism of injury, bodily injury severity, days post injury, age, number of deployments, theater where wounded, branch of service, and rank. Participants completed the Neurobehavioral Symptom Inventory (NSI) and the Posttraumatic Stress Disorder Checklist (PCL-C). There were no meaningful gender differences across all demographic and injury-related variables (p > 0.05). There were significant group differences and medium effect sizes for the NSI total score and all four NSI cluster scores. Symptoms most affected related to nausea, sensitivity to light, change in taste/smell, change in appetite, fatigue, and poor sleep. There were significant group differences and small-medium effect sizes for the PCL-C total score and two of the three PCL-C cluster scores. Symptoms most affected related to poor concentration, trouble remembering a stressful event, and disturbing memories/thoughts/images. Females consistently experienced more symptoms than males. As females become more active in combat related deployments, it is critical that future studies place more emphasis on this important military population. PMID- 27368357 TI - Induction of Direct or Priming Resistance against Botrytis cinerea in Strawberries by beta-Aminobutyric Acid and Their Effects on Sucrose Metabolism. AB - The specific forms of disease resistance induced by beta-aminobutyric acid (BABA) and their impacts on sucrose metabolism of postharvest strawberries were determined in the present research. Treatment with 10-500 mmol L(-1) BABA inhibited the Botrytis cinerea infection, possibly directly by suppressing the fungus growth and indirectly by triggering disease resistance. Moreover, BABA induced resistance against B. cinerea infection in strawberries was associated with either one of two mechanisms, depending upon the concentration used: BABA at concentrations higher than 100 mmol L(-1) directly induced the defense response, including a H2O2 burst, modulation of the expression of PR genes, including FaPR1, FaChi3, Fabetaglu, and FaPAL, and increased activities of chitinase, beta 1,3-glucanase, and PAL, whereas BABA at 10 mmol L(-1) activated a priming response because the BABA-treated fruits exhibited an increased capacity to express molecular defense only when the fruits were inoculated with B. cinerea. Activation of the priming defense appeared almost as effective against B. cinerea as inducing direct defense. However, the primed strawberries maintained higher activities of SS synthesis and SPS and SPP enzymes) and lower level of SS cleavage during the incubation; these activities contributed to higher sucrose, fructose, and glucose contents, sweetness index, and sensory scores compared to fruits exhibiting the direct defense. Thus, it is plausible that the priming defense, which can be activated by BABA at relatively low concentrations, represents an optimal strategy for combining the advantages of enhanced disease protection and soluble sugar accumulation. PMID- 27368358 TI - Beyond the Genetic Diagnosis: Providing Parents What They Want to Know. AB - Clinicians need to provide accurate, up-to-date, and balanced information to parents following a prenatal or postnatal diagnosis of Down syndrome and other genetic conditions. Families want information about the genomic outcomes and medical issues, but they also want information about life outcomes and social supports. Because the anticipated outcomes of a condition can change significantly based on available social support, health care, and services, it is important for clinicians to stay up-to-date about new developments and credible, medically reviewed information about Down syndrome and other genetic conditions to access resources for clinical care. PMID- 27368359 TI - Pediatric Coagulation Disorders. PMID- 27368360 TI - Pubertal Development. PMID- 27368361 TI - Case 1: Absent Pubertal Development in a 17.5-year-old Girl. PMID- 27368362 TI - Case 2: Prolonged Hypoglycemia in an Adolescent without Diabetes. PMID- 27368363 TI - Case 3: Penile Swelling in a 5-year-old Boy. PMID- 27368364 TI - New Alternative Tobacco Products - A Threat to Adolescent Health. PMID- 27368365 TI - Visual Diagnosis: 19-year-old Boy with Syncope and Bradycardia. PMID- 27368367 TI - Author's Response. PMID- 27368366 TI - Misconceptions in the Treatment of Dehydration in Children. PMID- 27368368 TI - Frontiers in lipid research: mechanisms, diet, and novel lipids. PMID- 27368369 TI - CardioPulse Articles. PMID- 27368370 TI - Spatial measurement errors in the field of spatial epidemiology. AB - BACKGROUND: Spatial epidemiology has been aided by advances in geographic information systems, remote sensing, global positioning systems and the development of new statistical methodologies specifically designed for such data. Given the growing popularity of these studies, we sought to review and analyze the types of spatial measurement errors commonly encountered during spatial epidemiological analysis of spatial data. METHODS: Google Scholar, Medline, and Scopus databases were searched using a broad set of terms for papers indexed by a term indicating location (space or geography or location or position) and measurement error (measurement error or measurement inaccuracy or misclassification or uncertainty): we reviewed all papers appearing before December 20, 2014. These papers and their citations were reviewed to identify the relevance to our review. RESULTS: We were able to define and classify spatial measurement errors into four groups: (1) pure spatial location measurement errors, including both non-instrumental errors (multiple addresses, geocoding errors, outcome aggregations, and covariate aggregation) and instrumental errors; (2) location-based outcome measurement error (purely outcome measurement errors and missing outcome measurements); (3) location-based covariate measurement errors (address proxies); and (4) Covariate-Outcome spatial misaligned measurement errors. We propose how these four classes of errors can be unified within an integrated theoretical model and possible solutions were discussed. CONCLUSION: Spatial measurement errors are ubiquitous threat to the validity of spatial epidemiological studies. We propose a systematic framework for understanding the various mechanisms which generate spatial measurement errors and present practical examples of such errors. PMID- 27368372 TI - Genome co-amplification upregulates a mitotic gene network activity that predicts outcome and response to mitotic protein inhibitors in breast cancer. AB - BACKGROUND: High mitotic activity is associated with the genesis and progression of many cancers. Small molecule inhibitors of mitotic apparatus proteins are now being developed and evaluated clinically as anticancer agents. With clinical trials of several of these experimental compounds underway, it is important to understand the molecular mechanisms that determine high mitotic activity, identify tumor subtypes that carry molecular aberrations that confer high mitotic activity, and to develop molecular markers that distinguish which tumors will be most responsive to mitotic apparatus inhibitors. METHODS: We identified a coordinately regulated mitotic apparatus network by analyzing gene expression profiles for 53 malignant and non-malignant human breast cancer cell lines and two separate primary breast tumor datasets. We defined the mitotic network activity index (MNAI) as the sum of the transcriptional levels of the 54 coordinately regulated mitotic apparatus genes. The effect of those genes on cell growth was evaluated by small interfering RNA (siRNA). RESULTS: High MNAI was enriched in basal-like breast tumors and was associated with reduced survival duration and preferential sensitivity to inhibitors of the mitotic apparatus proteins, polo-like kinase, centromere associated protein E and aurora kinase designated GSK462364, GSK923295 and GSK1070916, respectively. Co-amplification of regions of chromosomes 8q24, 10p15-p12, 12p13, and 17q24-q25 was associated with the transcriptional upregulation of this network of 54 mitotic apparatus genes, and we identify transcription factors that localize to these regions and putatively regulate mitotic activity. Knockdown of the mitotic network by siRNA identified 22 genes that might be considered as additional therapeutic targets for this clinically relevant patient subgroup. CONCLUSIONS: We define a molecular signature which may guide therapeutic approaches for tumors with high mitotic network activity. PMID- 27368371 TI - Rift Valley fever virus NSs protein functions and the similarity to other bunyavirus NSs proteins. AB - Rift Valley fever is a mosquito-borne zoonotic disease that affects both ruminants and humans. The nonstructural (NS) protein, which is a major virulence factor for Rift Valley fever virus (RVFV), is encoded on the S-segment. Through the cullin 1-Skp1-Fbox E3 ligase complex, the NSs protein promotes the degradation of at least two host proteins, the TFIIH p62 and the PKR proteins. NSs protein bridges the Fbox protein with subsequent substrates, and facilitates the transfer of ubiquitin. The SAP30-YY1 complex also bridges the NSs protein with chromatin DNA, affecting cohesion and segregation of chromatin DNA as well as the activation of interferon-beta promoter. The presence of NSs filaments in the nucleus induces DNA damage responses and causes cell-cycle arrest, p53 activation, and apoptosis. Despite the fact that NSs proteins have poor amino acid similarity among bunyaviruses, the strategy utilized to hijack host cells are similar. This review will provide and summarize an update of recent findings pertaining to the biological functions of the NSs protein of RVFV as well as the differences from those of other bunyaviruses. PMID- 27368375 TI - Is premeiotic genome elimination an exclusive mechanism for hemiclonal reproduction in hybrid males of the genus Pelophylax? AB - BACKGROUND: The ability to eliminate a parental genome from a eukaryotic germ cell is a phenomenon observed mostly in hybrid organisms displaying an alternative propagation to sexual reproduction. For most taxa, the underlying cellular pathways and timing of the elimination process is only poorly understood. In the water frog hybrid Pelophylax esculentus (parental taxa are P. ridibundus and P. lessonae) the only described mechanism assumes that one parental genome is excluded from the germline during metamorphosis and prior to meiosis, while only second genome enters meiosis after endoreduplication. Our study of hybrids from a P. ridibundus-P. esculentus-male populations known for its production of more types of gametes shows that hybridogenetic mechanism of genome elimination is not uniform. RESULTS: Using comparative genomic hybridization (CGH) on mitotic and meiotic cell stages, we identified at least two pathways of meiotic mechanisms. One type of Pelophylax esculentus males provides supporting evidence of a premeiotic elimination of one parental genome. In several other males we record the presence of both parental genomes in the late phases of meiotic prophase I (diplotene) and metaphase I. CONCLUSION: Some P. esculentus males have no genome elimination from the germ line prior to meiosis. Considering previous cytological and experimental evidence for a formation of both ridibundus and lessonae sperm within a single P. esculentus individual, we propose a hypothesis that genome elimination from the germline can either be postponed to the meiotic stages or absent altogether in these hybrids. PMID- 27368377 TI - Overzicht Van Het Hematologisch Kwaliteitskontrole 1973. AB - It appears from this Q.C. survey that automatic cel counting generally gives good results for erythrocytes, but somewhat less good results for white blood cells. Thrombocytic numeration however, gives unreliable and uncomparable results in a Q.C. survey, regardless of the method used, because of the extreme sensitivity of the platelets to a number of external factors, such as temperature, transportation, etc. As far as morphological examination is concerned it appears that many observers pay too little attention to morphological abnormalities of the erythrocytes. The results with blood group serology point to some difficulties with Rh-factor determination. PMID- 27368373 TI - Next-generation sequencing diagnostics of bacteremia in septic patients. AB - BACKGROUND: Bloodstream infections remain one of the major challenges in intensive care units, leading to sepsis or even septic shock in many cases. Due to the lack of timely diagnostic approaches with sufficient sensitivity, mortality rates of sepsis are still unacceptably high. However a prompt diagnosis of the causative microorganism is critical to significantly improve outcome of bloodstream infections. Although various targeted molecular tests for blood samples are available, time-consuming blood culture-based approaches still represent the standard of care for the identification of bacteria. METHODS: Here we describe the establishment of a complete diagnostic workflow for the identification of infectious microorganisms from seven septic patients based on unbiased sequence analyses of free circulating DNA from plasma by next-generation sequencing. RESULTS: We found significant levels of DNA fragments derived from pathogenic bacteria in samples from septic patients. Quantitative evaluation of normalized read counts and introduction of a sepsis indicating quantifier (SIQ) score allowed for an unambiguous identification of Gram-positive as well as Gram negative bacteria that exactly matched with blood cultures from corresponding patient samples. In addition, we also identified species from samples where blood cultures were negative. Reads of non-human origin also comprised fragments derived from antimicrobial resistance genes, showing that, in principle, prediction of specific types of resistance might be possible. CONCLUSIONS: The complete workflow from sample preparation to species identification report could be accomplished in roughly 30 h, thus making this approach a promising diagnostic platform for critically ill patients suffering from bloodstream infections. PMID- 27368376 TI - An evolutionary perspective on the necroptotic pathway. AB - Throughout the animal kingdom, innate immune receptors protect the organism from microbial intruders by activating pathways that mediate inflammation and pathogen clearance. Necroptosis contributes to the innate immune response by killing pathogen-infected cells and by alerting the immune system through the release of danger signals. Components of the necroptotic signaling axis - TIR-domain containing adapter-inducing interferon-beta (TRIF), Z-DNA sensor DAI, receptor interacting kinase (RIPK)1, RIPK3 and mixed-lineage kinase domain-like protein (MLKL) - are therefore expected to be found in all animals. However, a phylogenetic analysis reveals that the necroptotic axis, except for RIPK1, is poorly conserved in the animal kingdom, suggesting that alternative mechanisms regulate necroptosis in these species or that necroptosis would apparently be absent. These findings question the universal role of necroptosis during innate immunity in the animal kingdom. PMID- 27368374 TI - Investigation of allosteric coupling in human beta2-adrenergic receptor in the presence of intracellular loop 3. AB - BACKGROUND: This study investigates the allosteric coupling that exists between the intra- and extracellular parts of human beta2-adrenergic receptor (beta2-AR), in the presence of the intracellular loop 3 (ICL3), which is missing in all crystallographic experiments and most of the simulation studies reported so far. Our recent 1 MUs long MD run has revealed a transition to the so-called very inactive state of the receptor, in which ICL3 packed under the G protein's binding cavity and completely blocked its accessibility to G protein. Simultaneously, an outward tilt of transmembrane helix 5 (TM5) caused an expansion of the extracellular ligand-binding site. In the current study, we performed independent runs with a total duration of 4 MUs to further investigate the very inactive state with packed ICL3 and the allosteric coupling event (three unrestrained runs and five runs with bond restraints at the ligand-binding site). RESULTS: In all three independent unrestrained runs (each 500 ns long), ICL3 preserved its initially packed/closed conformation within the studied time frame, suggesting an inhibition of the receptor's activity. Specific bond restraints were later imposed between some key residues at the ligand-binding site, which have been experimentally determined to interact with the ligand. Restraining the binding site region to an open state facilitated ICL3 closure, whereas a relatively constrained/closed binding site hindered ICL3 packing. However, the reverse operation, i.e. opening of the packed ICL3, could not be realized by restraining the binding site region to a closed state. Thus, any attempt failed to free the ICL3 from its locked state due to the presence of persistent hydrogen bonds. CONCLUSIONS: Overall, our simulations indicated that starting with very inactive states, the receptor stayed almost irreversibly inhibited, which in turn decreased the overall mobility of the receptor. Bond restraints which represented the geometric restrictions caused by ligands of various sizes when bound at the ligand-binding site, induced the expected conformational changes in TM5, TM6 and consequently, ICL3. Still, once ICL3 was packed, the allosteric coupling became ineffective due to strong hydrogen bonds connecting ICL3 to the core of the receptor. PMID- 27368378 TI - The Position Of National Surveys In Proficiency Testing Of Clinical Chemistry Laboratories. AB - Results of the Belgian proficiency surveys (1971-1973) for clinical chemistry labs are reported. The specific position of this external type of quality control is analyzed. Special attention is given to the detection of systematic factors that could interfere with the introduction of a uniform medical record. A new procedure is described for displaying results grouped according to methods. The difference between the main methods in actual use is of the systematic type rather than a difference in precision. The Youden approach to collaborative tests has been elaborated and generalized by the introduction of correla-tion as an expression of the incidence of systematic factors. The shape of the contour encompassing 95% of the Youden couples, defines a target area often very different from the circular surface expected with uncorrelated results. The participating laboratories, as a group, appeared to work from the beginning according to the current state of the art. Improvement is only possible if basic changes in methods or in calibration are introduced. This suggests a broadening of the activities of the Belgian Society for Quality Control. PMID- 27368379 TI - L'Alimentation Parenterale. AB - One of the essential requisites of the treatment of catabolism inducing diseases is the maintenance of an adequate nutritional status. When this cannot be achieved by the usual means (normal or forcible feeding), it is necessary to have recourse to parenteral nutrition. An adequate supply of nitrogen, ions, water and calories can either totally replace or complete the feeding and restore a satisfactory nutritional equilibrium, even in cases of cachectic diseases. The nutritional program must comply with the following criteria: 1. The caloric needs of the patient, which can be considerable, have to be met: an average of 2,500 to 4,000 calories per day including 12 to 20 gm nitrogen. 2. At least 10% of this amount must be given as carbohydrates. 3. The nitrogen is supplied by protein hydrolysate or synthetic amino-acid perfusions. The optimal proportions between all the amino-acids (essentials and non essentials) must be accurately kept to. In order to achieve the best protein anabolism, 150 to 300 calories should be given per gm of nitrogen perfused. This may be achieved by associating carbohydrates with the protein perfusions and by simultaneous perfusion of a lipid emulsion or of a concentrated glucose preparation. 4. Two to three gm lipids per kilo per day should be administered. Some lipid emulsions are well tolerated (soya oil emulsified by egg yolk phosphatides) and make a considerable caloric contribution possible. 5. The needs of water and ions have to be adapted to each individual case. Vitamins are an essential part of prolonged parenteral nutrition. Parenteral nutrition is frequently indicated. It is practically inocuous. However, care is needed when administering lipid emulsions to hepatic patients. It is to be noted that the high caloric lipid emulsions or protein containing solutions at present available in Belgium are not those generally indicated. The introduction into our country of soya oil emulsions as well as new protein solutions better balanced in the relative proportions of the different amino-acids as well as in their nitrogen-caloric ratio will be a notable step forward in what has been hitherto a neglected aspect of the treatment: the maintenance of the patient in optimal nutritional status. PMID- 27368380 TI - Selected Summaries. PMID- 27368382 TI - [Not Available]. PMID- 27368383 TI - [Not Available]. PMID- 27368384 TI - [Not Available]. PMID- 27368385 TI - [Not Available]. PMID- 27368386 TI - [Not Available]. PMID- 27368387 TI - [Not Available]. PMID- 27368388 TI - [Not Available]. PMID- 27368390 TI - [Not Available]. PMID- 27368389 TI - [Not Available]. PMID- 27368391 TI - [Not Available]. PMID- 27368392 TI - [Not Available]. PMID- 27368393 TI - [Not Available]. PMID- 27368394 TI - [Not Available]. PMID- 27368395 TI - [Not Available]. PMID- 27368396 TI - [Not Available]. PMID- 27368397 TI - [Not Available]. PMID- 27368398 TI - [Not Available]. PMID- 27368399 TI - [Not Available]. PMID- 27368400 TI - [Not Available]. PMID- 27368401 TI - [Not Available]. PMID- 27368403 TI - [Not Available]. PMID- 27368402 TI - [Not Available]. PMID- 27368404 TI - [Not Available]. PMID- 27368405 TI - [Not Available]. PMID- 27368406 TI - [Not Available]. PMID- 27368407 TI - [Not Available]. PMID- 27368408 TI - [Not Available]. PMID- 27368409 TI - Extractable and Non-Extractable Phenolics and Antioxidant Capacity of Mandarin Waste Dried at Different Temperatures. AB - The mandarin industry is generating more waste due to the increasing demand for juice. In this study, extractable and non-extractable phenolics as well as 2,2 diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6 sulphonic acid) (ABTS), ferric reducing ability of plasma (FRAP), and oxygen radical absorbance capacity (ORAC) antioxidant activities in Satsuma mandarin waste dried at different temperatures were determined. The amounts of non extractable total phenols, total flavonoids, and condensed tannins measured in mandarin waste dried at 120 degrees C were 39.4, 44.3, and 45.6 %, respectively, which were higher than those of fresh-mandarin waste. Dried mandarin waste is rich in extractable and non-extractable hesperidin (259.86 and 182.52 mg/g, respectively) and eriocitrin (85.12 and 197.24 mg/g, respectively), as well as non-extractable gallic acid (36.08 MUg/g). The antioxidant capacities of extractable and non-extractable phenolics, from the highest to the lowest, were ABTS > ORAC > DPPH > FRAP and ORAC > ABTS > DPPH > FRAP, respectively. The information reported here may encourage mandarin industry operators to re evaluate their by-products, extending the application of mandarin fruits and reducing waste. PMID- 27368410 TI - Effect of Germination and Fermentation Process on the Antioxidant Compounds of Quinoa Seeds. AB - Quinoa (Chenopodium quinoa) seed has gained a great interest in the last years, mainly due to its nutritional properties and its content of antioxidant substances with health-promoting properties in humans. In this work, the effect of germination time and fermentation on the levels of antioxidant compounds (ascorbic acid, tocopherol isomers and phenolic compounds) and antioxidant activity of quinoa seeds was evaluated. Fermentation was carried out naturally by the microorganisms present in the seeds or by inoculation with two Saccharomyces cerevisiae strains (used for baking and brewing). Ascorbic acid and total tocopherols were significantly increased (p <= 0.05) after 72 h of germination process in comparison with raw quinoa seeds, whilst fermentation caused a decrease in both types of compounds. Phenolic compounds and antioxidant capacity were improved using both bioprocesses, being this effect more noticeable for germination process (101 % of increase after three days of germination). Germination and fermentation proved to be desirable procedures for producing enriched ingredients with health-promoting antioxidant compounds in a natural way. PMID- 27368411 TI - Invariant natural killer T cells: front line fighters in the war against pathogenic microbes. AB - Invariant natural killer T (iNKT) cells constitute a unique subset of innate-like T cells that have been shown to have crucial roles in a variety of immune responses. iNKT cells are characterized by their expression of both NK cell markers and an invariant T cell receptor (TCR) alpha chain, which recognizes glycolipids presented by the MHC class I-like molecule CD1d. Despite having a limited antigen repertoire, the iNKT cell response can be very complex, and participate in both protective and harmful immune responses. The protective role of these cells against a variety of pathogens has been particularly well documented. Through the use of these pathogen models, our knowledge of the breadth of the iNKT cell response has been expanded. Specific iNKT cell antigens have been isolated from several different bacteria, from which iNKT cells are critical for protection in mouse models. These responses can be generated by direct, CD1d-mediated activation, or indirect, cytokine-mediated activation, or a combination of the two. This can lead to secretion of a variety of different Th1, Th2, or Th17 cytokines, which differentially impact the downstream immune response against these pathogens. This critical role is emphasized by the conservation of these cells between mice and humans, warranting further investigation into how iNKT cells participate in protective immune responses, with the ultimate goal of harnessing their potential for treatment. PMID- 27368412 TI - Evolution of innate-like T cells and their selection by MHC class I-like molecules. AB - Until recently, major histocompatibility complex (MHC) class I-like-restricted innate-like alphabetaT (iT) cells expressing an invariant or semi-invariant T cell receptor (TCR) repertoire were thought to be a recent evolutionary acquisition restricted to mammals. However, molecular and functional studies in Xenopus laevis have demonstrated that iT cells, defined as MHC class I-like restricted innate-like alphabetaT cells with a semi-invariant TCR, are evolutionarily conserved and prominent from early development in amphibians. As these iT cells lack the specificity conferred by conventional alphabeta TCRs, it is generally considered that they are specialized to recognize conserved antigens equivalent to pathogen-associated molecular patterns. Thus, one advantage offered by the MHC class I-like iT cell-based recognition system is that it can be adapted to a common pathogen and function on the basis of a relatively small number of T cells. Although iT cells have only been functionally described in mammals and amphibians, the identification of non-classical MHC/MHC class I-like genes in other groups of endothermic and ectothermic vertebrates suggests that iT cells have a broader phylogenetic distribution than previously envisioned. In this review, we discuss the possible role of iT cells during the emergence of the jawed vertebrate adaptive immune system. PMID- 27368415 TI - Icariin, a major constituent from Epimedium brevicornum, attenuates ibotenic acid induced excitotoxicity in rat hippocampus. AB - Excitotoxicity is one of the most extensively studied causes of neuronal death and plays an important role in Alzheimer's disease (AD). Icariin is a flavonoid component of a traditional Chinese medicine reported to possess a broad spectrum of pharmacological effects. The present study was designed to investigate the effects of icariin against learning and memory impairment induced by excitotoxicity. Here, we demonstrated that rats receiving intracerebroventricular injection of excitatory neurotoxin ibotenic acid exhibited impaired learning and memory. Oral administration of icariin at doses of 20 and 40mg/kg rescued behavioral performance and protected against neurotoxicity in rat hippocampus by suppressing ibotenic acid induced pro-apoptosis. Furthermore, Western blott of hippocampal specimens revealed that icariin up-regulated the expression of calbindin-D28k protein following ibotenic acid administration. Additionally, icariin inhibited mitogen-activated protein kinase (MAPK) family phosphorylation and nuclear factor kappa B (NF-kappaB) signaling, implicating the MAPK signaling and NF-kappaB signaling pathways were involved in the mechanism underlying icariin-mediated neuroprotection against ibotenic acid-induced excitotoxicity. These data suggested that icariin could be a potential agent for treatment of excitotoxicity-related diseases, including AD. PMID- 27368413 TI - The role of MHC class Ib-restricted T cells during infection. AB - Even though major histocompatibility complex (MHC) class Ia and many Ib molecules have similarities in structure, MHC class Ib molecules tend to have more specialized functions, which include the presentation of non-peptidic antigens to non-classical T cells. Likewise, non-classical T cells also have unique characteristics, including an innate-like phenotype in naive animals and rapid effector functions. In this review, we discuss the role of MAIT and NKT cells during infection but also the contribution of less studied MHC class Ib restricted T cells such as Qa-1-, Qa-2-, and M3-restricted T cells. We focus on describing the types of antigens presented to non-classical T cells, their response and cytokine profile following infection, as well as the overall impact of these T cells to the immune system. PMID- 27368416 TI - Attentional updating and monitoring and affective shifting are impacted independently by aging in macaque monkeys. AB - One hallmark of the normal cognitive aging process involves alterations in executive function. Executive function can be divided into at least three separable components, including set shifting, attentional updating and monitoring, and inhibition of prepotent responses. The ability to study the neural basis of cognitive aging has been enriched by the use of animal models such as the macaque monkey. In aged macaques, changes in attentional updating and monitoring systems are poorly understood compared to changes in shifting and inhibition. A partial explanation for this is the fact that the tasks designed to study executive function in aged monkeys, to date, primarily have probed shifting and inhibition processes. Here we examine how aging impacts attentional updating and monitoring processes in monkeys using an interference task designed after a paradigm used to examine multi-tasking in older humans. Young and aged macaque monkeys were tested on this interference task as well as on an object reversal learning task to study these processes in the same animals. Relative to the young monkeys, aged animals were impaired on both tasks. Proactive and retroactive interference did not differ between age groups on an array of 40 object pairs presented each day in the object reversal learning task. The levels of performance on the interference task were not correlated with levels of performance in the object reversal task. These results suggest that attentional updating and monitoring and affective shifting are separable functions in the macaque, and that normal aging affects these mental operations independently. PMID- 27368414 TI - The CD1 family: serving lipid antigens to T cells since the Mesozoic era. AB - Class I-like CD1 molecules are in a family of antigen-presenting molecules that bind lipids and lipopeptides, rather than peptides for immune surveillance by T cells. Since CD1 lacks the high degree of polymorphism found in their major histocompatibility complex (MHC) class I molecules, different species express different numbers of CD1 isotypes, likely to be able to present structurally diverse classes of lipid antigens. In this review, we will present a historical overview of the structures of the different human CD1 isotypes and also discuss species-specific adaptations of the lipid-binding groove. We will discuss how single amino acid changes alter the shape and volume of the CD1 binding groove, how these minor changes can give rise to different numbers of binding pockets, and how these pockets affect the lipid repertoire that can be presented by any given CD1 protein. We will compare the structures of various lipid antigens and finally, we will discuss recognition of CD1-presented lipid antigens by antigen receptors on T cells (TCRs). PMID- 27368419 TI - Stabilization of C-RAF:KSR1 complex by DiRas3 reduces availability of C-RAF for dimerization with B-RAF. AB - RAF family kinases are central components of the Ras-RAF-MEK-ERK cascade. Dimerization is a key mechanism of RAF activation in response to physiological, pathological and pharmacological signals. It is mediated by a dimer interface region in the RAF kinase domain that is also conserved in KSR, a scaffolding protein that binds RAF, MEK and ERK. The regulation of RAF dimerization is incompletely understood. Especially little is known about the molecular mechanism involved in the selection of the dimerization partner. Previously, we reported that Ras-dependent binding of the tumour suppressor DiRas3 to C-RAF inhibits the C-RAF:B-RAF heterodimerization. Here we show that DiRas3 binds to KSR1 independently of its interaction with activated Ras and RAF. Our data also suggest that depending on the local stoichiometry between DiRas3 and oncogenic Ras, DiRas3 can either enhance homodimerization of KSR1 or recruit KSR1 to the Ras:C-RAF complex and thereby reduce the availability of C-RAF for binding to B RAF. This mechanism, which is shared between A-RAF and C-RAF, may be involved in the regulation of Ras12V-induced cell transformation by DiRas3. PMID- 27368418 TI - A comparison of progestins within three classes: Differential effects on learning and memory in the aging surgically menopausal rat. AB - INTRODUCTION: For decades, progestins have been included in hormone therapies (HT) prescribed to women to offset the risk of unopposed estrogen-induced endometrial hyperplasia. However, the potential effects on cognition of subcategories of clinically used progestins have been largely unexplored. METHODS: In two studies, the present investigation evaluated the cognitive effects of norethindrone acetate (NETA), levonorgestrel (LEVO), and medroxyprogesterone acetate (MPA) on the water radial-arm maze (WRAM) and Morris water maze (MM) in middle-aged ovariectomized rats. RESULTS: In Study 1, six weeks of a high-dose NETA treatment impaired learning and delayed retention on the WRAM, and impaired reference memory on the MM. Low-dose NETA treatment impaired delayed retention on the WRAM. In Study 2, high-dose NETA treatment was reduced to four-weeks and compared to MPA and LEVO. As previously shown, MPA impaired working memory performance during the lattermost portion of testing, at the highest working memory load, impaired delayed retention on the WRAM, and impaired reference memory on the MM. NETA also impaired performance on these WRAM and MM measures. Interestingly, LEVO did not impair performance, but instead enhanced learning on the WRAM. CONCLUSIONS: The current study corroborates previous evidence that the most commonly prescribed FDA-approved progestin for HT, MPA, impairs learning and memory in the ovariectomized middle-aged rat. When progestins from two different additional subcategories were investigated, NETA impaired learning and memory similarly to MPA, but LEVO enhanced learning. Future research is warranted to determine LEVO's potential as an ideal progestin for optimal health in women, including for cognition. PMID- 27368417 TI - A novel mouse model of the aged brain: Over-expression of the L-type voltage gated calcium channel CaV1.3. AB - The aged population is growing rapidly, which has sparked tremendous interest in elucidating mechanisms of aging in both the body and the brain. Animal models have become an indispensable tool in biomedical science, but because of the cost and extended timeframe associated with aging animals to appropriate time points, studies that rely on using aged animals are often not feasible. Somewhat surprisingly, there are relatively few animal models that have been specifically engineered to mimic physiological changes known to occur during "normal" aging. Developing transgenic animal models that faithfully mimic key aspects of aging would likely be of great utility in studying both age-related deficits in the absence of overt pathology as well as an adjunct for transgenic models of diseases where aging is a primary risk factor. In particular, there are several alterations in the aged brain that are amenable to being modeled genetically. We have focused on one key aspect that has been repeatedly demonstrated in aged animals - an increase in the L-type voltage-gated calcium channel CaV1.3. Here we present a novel transgenic mouse line in which expression of CaV1.3 is increased by approximately 50% in the forebrain of young mice. These mice do not display any overt physical or non-cognitive deficits, exhibiting normal exploratory behavior, motor function, and affective-like responses, suggesting that these mice can be successfully deployed to assess the impact of an "aged brain" in a variety of conditions. PMID- 27368420 TI - [Acute pericarditis and stent infection]. PMID- 27368421 TI - Increased HIV-1 sensitivity to neutralizing antibodies by mutations in the Env V3 coding region for resistance to CXCR4 antagonists. AB - HIV-1 passage in cell culture in the presence of chemokine receptor antagonists can result in selection of viruses with env mutations that confer resistance to these inhibitors. In the present study, we examined the effect of HIV-1env mutations that confer resistance to CXCR4 antagonists on envelope (Env) sensitivity to neutralizing antibodies (NAbs). Serial passage of CXCR4-tropic HIV 1 NL4-3 in PM1/CCR5 cells under CXCR4 antagonists KRH-3955, AMD3100 and AMD070 yielded two KRH-3955-resistant, one AMD3100-resistant and one AMD070-resistant viruses. These viruses had multiple env mutations including the Env gp120 V3 region. The majority of viruses having these CXCR4 antagonist-resistant Envs showed higher sensitivity to NAbs 447-52D, b12 and 2F5 targeting the V3 region, the gp120 CD4-binding site and the gp41 membrane proximal region, respectively, compared to NL4-3 WT virus. Recombinant NL4-3 viruses with the V3-coding region replaced with those derived from the CXCR4 antagonist-resistant viruses showed increased sensitivity to NAbs b12, 2F5 and 447-52D. Molecular dynamics simulations of Env gp120 outer domains predicted that the V3 mutations increased levels of fluctuations at the tip and stem of the V3 loop. These results indicate that mutations in the V3-coding region that result in loss of viral sensitivity to CXCR4 antagonists increase viral sensitivity to NAbs, providing insights into our understanding of the interplay of viral Env accessibility to chemokine receptors and sensitivity to NAbs. PMID- 27368422 TI - Impact of Surface Chemistry on Copper Deposition in Mesoporous Silicon. AB - An easy, efficient, and safe process is developed to metallize mesoporous silicon (PSi) with Cu from the decomposition of a solution of mesitylcopper (CuMes) in an imidazolium-based ionic liquid (IL), [C1C4Im][NTf2]. The impregnation of a solution of CuMes in IL affords the deposition of metallic islands not only on the surface but also deep within the pores of a mesoporous Si layer with small pores below 10 nm. Therefore, this process is well suited to efficiently and completely metallize PSi layers. An in-depth mechanistic study shows that metal deposition is due to the reduction of CuMes by surface silane groups rather than by Si oxidation as observed in aqueous or water-containing media. This could open a new route to the chemical metallization of PSi by less-noble metals difficult to attain by a conventional displacement reaction. PMID- 27368423 TI - Erectile dysfunction patients are more satisfied with penile prosthesis implantation compared with tadalafil and intracavernosal injection treatments. AB - There are various treatment modalities for erectile dysfunction with different success and satisfaction rates. We aim to compare patient satisfaction with tadalafil, intracavernosal injection, and penile prosthesis implantation in patients with erectile dysfunction. The records of 3448 men with erectile dysfunction were evaluated retrospectively. A total of 356 men with organic erectile dysfunction were enrolled into this study. Of these patients, 132 (37%) received tadalafil 20 mg twice a week for 12 weeks, 106 (30%) patients received tadalafil 5 mg once-daily for 12 weeks, 96 (27%) patients used intracavernosal injection therapy (Bi-mix; papaverine and phentolamine). Moreover, 22 patients underwent penile prosthesis implantation. Patient and partner satisfaction were assessed with International Index of Erectile Function (IIEF) and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire. Patients' mean age was 52.4 +/- 25.76 (32-71). The etiology of erectile dysfunction was chronic systemic diseases in 133 (44%) and radical prostatectomy in 121 patients (40%). The mean IIEF-5 scores improvement after the treatment was higher in penile prosthesis implantation group (12.4 +/- 1.3) compared with tadalafil 5 mg (6.7 +/- 1.5) (p < 0.01), tadalafil 20 mg (6.2 +/- 1.5) (p < 0.01), and intracavernosal injection group (8.4 +/- 3.2) (p < 0.05). The EDITS score was significantly higher in penile prosthesis implantation group (78.2 +/- 11.3) compared with intracavernosal injection (60.3 +/- 6.3), tadalafil 5 mg (72.5 +/- 4.5), and tadalafil 20 mg 70.7 +/- 3.4 groups (p < 0.05). Partners' EDITS scores were 70.1 +/- 10 in penile prosthesis implantation group, 50.2 +/- 1.5 in intracavernosal injection group, 62.9 +/- 7.8 in tadalafil 5 mg, and 61.3 +/- 5.3 in tadalafil 20 mg group (p < 0.05). Erectile dysfunction patients who underwent penile prosthesis implantation seem to be more satisfied compared with tadalafil treatment and intracavernosal injection. Future clinical trials are warranted to confirm our results. PMID- 27368424 TI - Twenty-four-hour work shifts, increased job demands, and elevated blood pressure in professional firefighters. AB - PURPOSE: To investigate whether working conditions (number of 24-h shifts, number of calls, sedentary work, job strain, effort-reward imbalance, and physical demands) are associated with elevated blood pressure and hypertension among professional firefighters. METHODS: A total of 330 (321 males and 9 females) firefighters were chosen for this study among the Southern California firefighters who participated in a work and obesity project. Working conditions were measured with a firefighter-specific occupational health questionnaire. Blood pressure was clinically assessed, and hypertension was defined according to the contemporary standard classification. RESULTS: About 11 % of the firefighters had hypertension. Fifty percent of the hypertensive firefighters (mostly mild hypertensive) had uncontrolled high blood pressure. Hypertension was more prevalent in male, older, and high-rank firefighters and firefighter who reported low numbers of daily calls. In male firefighters who were normotensive or hypertensive without taking anti-hypertensive medication, additional 24-h shifts in the past month increased the risk of elevated diastolic blood pressure (DBP) than those who reported a standard work schedule (eight to eleven 24-h shifts). Particularly, firefighters who reported sixteen 24-h shifts had 5.0 mmHg higher DBP (p < 0.01). Body mass index attenuated the association between number of shifts and blood pressure to some extent. Firefighters who reported "increased job demands over the past years" had 3.0 mmHg (p = 0.06) higher systolic blood pressure. Other working conditions were not associated with elevated blood pressure and hypertension. CONCLUSIONS: Many additional 24-h shifts and increased job demands were risk factors for elevated blood pressure in male firefighters. Optimal collective and individual workload and improved hypertension management are warranted for enhancing the cardiovascular health of firefighters. PMID- 27368425 TI - Does age matter in predicting musculoskeletal disorder risk? An analysis of workplace predictors over 4 years. AB - BACKGROUND: Musculoskeletal disorders (MSDs) are a major workplace issue. With increasing pressure to extend working lives, predictors of MSD risk across all age groups require accurate identification to inform risk reduction strategies. METHODS: In 2005 and 2009, a survey was conducted in a Finnish food processing company (N = 734). Data on workplace physical and psychosocial hazards, work ability, job satisfaction and lifestyle-related variables were collected, and MSD risk was measured through assessment of work-related strain in four body areas. Predictors of MSD risk across three age groups (20-35, 36-49, 50+) were assessed with linear regression analysis. RESULTS: Physical hazards and MSD risk were related differently for each age group. The relationship between psychosocial hazards and MSD risk was less clear. For younger workers, physical hazards were not associated with MSD risk. In contrast, for those aged 36-49, repetitive movements (B = 1.76, p < 0.001) and awkward postures (B = 1.30, p = 0.02) were associated with increased MSD risk. For older workers, environmental hazards were positively associated with MSD risk (B = 0.37, p = 0.04). Predictors of MSD risk changed differently for each age group during 4 years of follow-up. For younger workers, change in environment and repetitive movements, for middle age team support and for older workers change in awkward posture were significant predictors of MSD risk. CONCLUSIONS: These results support the need for workplace specific hazard surveillance data. This will ensure that all contributing factors to MSD risk can be accurately identified and controlled independent of age. PMID- 27368426 TI - Developmental and Environmental Effects on Sesquiterpene Lactones in Cultivated Arnica montana L. AB - The amount of sesquiterpene lactones and the lactone profile of Arnica montana L. in flowering and seed formation stages in vitro and in vivo propagated from seeds of German, Ukrainian, and Austrian origin and grown in two experimental fields were studied. It was found that in vitro propagated 2-year plants in full flowering stage accumulated higher amount of lactones in comparison to in vivo propagated 3-year plants and to the seed formation stage, respectively. Helenalins predominated in in vivo propagated 2-year or in vitro propagated 3 year plants. 2-Methylbutyrate (2MeBu) was the principal ester in the samples with prevalence of helenalins, while isobutyrate (iBu) was the major one in the samples with predominance of 11,13-dihydrohelenalins. The results revealed that the environmental conditions on Vitosha Mt. are more suitable for cultivation of A. montana giving higher content of lactones. PMID- 27368427 TI - Obsessive-compulsive disorder: The usefulness of a pharmacological practice guideline. PMID- 27368429 TI - The heart of the matter is brain: Monitoring cerebrovascular autoregulation after cardiac arrest. PMID- 27368428 TI - Admission of out-of-hospital cardiac arrest victims to a high volume cardiac arrest center is linked to improved outcome. AB - AIM: Cardiac arrest centers have been associated with improved outcome for patients after cardiac arrest. Aim of this study was to investigate the effect on outcome depending on admission to high-, medium- or low volume centers. METHODS: Analysis from a prospective, multicenter registry for out of hospital cardiac arrest patients treated by the emergency medical service of Vienna, Austria. The frequency of cardiac arrest patients admitted per center/year (low <50; medium 50 100; high >100) was correlated to favorable outcome (30-day survival with cerebral performance category of 1 or 2). RESULTS: Out of 2238 patients (years 2013-2015) with emergency medical service resuscitation, 861 (32% female, age 64 (51;73) years) were admitted to 7 different centers. Favorable outcome was achieved in 267 patients (31%). Survivors were younger (58 vs. 66 years; p<0.001), showed shockable initial heart rhythm more frequently (72 vs. 35%; p<0.001), had shorter CPR durations (22 vs. 29min; p<0.001) and were more likely to be treated in a high frequency center (OR 1.6; CI: 1.2-2.1; p=0.001). In multivariate analysis, age below 65 years (OR 15; CI: 3.3-271.4; p=0.001), shockable initial heart rhythm (OR 10.1; CI: 2.4-42.6; p=0.002), immediate bystander or emergency medical service CPR (OR 11.2; CI: 1.4-93.3; p=0.025) and admission to a center with a frequency of >100 OHCA patients/year (OR 5.2; CI: 1.2-21.7; p=0.025) was associated with favorable outcome. CONCLUSIONS: High frequency of post-cardiac arrest treatment in a specialized center seems to be an independent predictor for favorable outcome in an unselected population of patients after out of hospital cardiac arrest. PMID- 27368430 TI - Heart rate response to therapeutic hypothermia in infants with hypoxic-ischaemic encephalopathy. AB - AIM OF THE STUDY: Neonatal encephalopathy (NE) of hypoxic-ischaemic origin may cause death or life-long disability which is reduced by therapeutic hypothermia (TH). Our objective was to assess HR response in infants undergoing TH after perinatal asphyxia. METHODS: We performed a retrospective case series, from a single-centre tertiary care NICU. We included ninety-two infants with NE of likely hypoxic-ischaemic origin, moderate or severe, treated with TH (n=60) or normothermia (n=32) who had 18 month outcome data and at least 12 HR recordings the first 24h after birth (1998-2010) Bristol, UK. Poor outcome was defined as death or severe disability. Data are reported as medians and 95% confidence intervals (CI). RESULTS: TH to 33.5 degrees C decreased HR by 30bpm to 92bpm (95% CI: 88, 96) 12h after birth in infants with NE and good outcome as compared to infants treated at normothermia 118bpm (95% CI: 110, 130). Despite constant low rectal temperature, HR increased gradually during cooling from 36 to 72h to 97bpm (89, 106) approaching the normothermia group, 117bpm (96, 133). During TH, infants with poor outcome had higher HR at 12h after birth (112bpm, 95% CI: 92, 115) as compared to infants with good outcome (p=0.004). Inotropic support increased HR by 17bpm in infants with good outcome and by 22bpm in infants with poor outcome. CONCLUSIONS: In NE, TH decreases HR the first day of life. HR remained lower during TH, but increased during the last day of TH. Infants with poor outcome have higher HR. PMID- 27368431 TI - 2016 World Congress on In Vitro Biology, June 11-15, San Diego, California : Late Submission Abstracts. PMID- 27368433 TI - Nerve-independent and ectopically additional induction of taste buds in organ culture of fetal tongues. AB - An improved organ culture system allowed to observe morphogenesis of mouse lingual papillae and taste buds relatively for longer period, in which fetal tongues were analyzed for 6 d. Taste cells were defined as eosinophobic epithelial cells expressing CK8 and Sox2 within lingual epithelium. Addition of glycogen synthase kinase 3 beta inhibitor CHIR99021 induced many taste cells and buds in non-gustatory and gustatory stratified lingual epithelium. The present study clearly demonstrated induction of taste cells and buds ectopically and without innervation. PMID- 27368432 TI - Therapeutic potential of compound K as an IKK inhibitor with implications for osteoarthritis prevention: an in silico and in vitro study. AB - Ginsenosides have been used traditionally as an oriental medicine. However, the anti-osteoarthritic effect of ginsenoside compound K (hereafter referred to as CK) has not been reported. Therefore, in this study, the protective effects of CK were evaluated in silico and in vitro using H2O2-stimulated MC3T3-E1 cells by measuring the levels of proinflammatory cytokines responsible for articular cartilage degradation. In silico results demonstrated that, among the selected ginsenosides, CK is a non-toxic drug-like molecule with strong binding affinity for selected cytokine-activated kinase such as IkBalpha kinase (IKK). The molecular binding energy of CK with the active sites of IKK suggests anti osteoarthritic functions. Cultured H2O2-stimulated MC3T3-E1 cells that were exposed to CK showed dramatically increased expression of osteoblast differentiation markers such as alkaline phosphatase (ALP) activity, type I collagen (Col-I) content, and mineralization. During aging, H2O2 also leads to the production of reactive oxygen species (ROS) and nitric oxide (NO), which play important roles in the development of osteoarthritis (OA). Therefore, the effect of CK on ROS and NO generation was also examined. Our results showed that CK dose dependently inhibited H2O2-induced ROS and NO production in MC3T3-E1 cells. Moreover, qRT-PCR data showed that CK increased expression of osteogenic markers such as ALP and Col-I but decreased expression of inflammatory-related genes including IKK and interleukin 1beta (IL-1beta) in a dose-dependent manner in H2O2 stimulated MC3T3-E1 cells. The findings of this study suggest the use of CK as a novel protective and therapeutic agent in AO. PMID- 27368434 TI - FCN2 c.772G>T polymorphism is associated with chronic adenoiditis and/or tonsillitis, but not -4 A>G and -602 G>A. AB - OBJECTIVE: Ficolins are complement activating peptides that play a role in the initial host defense against infectious pathogens. In the present study, we investigated the relationship between single nucleotide polymorphisms (SNPs) in the ficolin 2 gene (FCN2) and chronic adenotonsillitis in pediatric cases. STUDY DESIGN: Case-control study. METHODS: A total of 101 pediatric patients diagnosed with chronic adenotonsillitis and 100 healthy children were enrolled in the study. Genotypes of FCN2 promoter SNPs - 602 G>A and -4 A>G, and the exonic SNP c.772G>T were determined by light SNP assay after realtime PCR analysis using genomic DNA samples obtained from peripheral blood samples of all participants. RESULTS: Of the 101 chronic tonsillitis patients, 38 were girls and 63 were boys; the mean age was 5.2 +/- 2.3 years. The c.772G>T SNP frequency was significantly higher in chronic adenotonsillitis cases compared to the control group (p = 0.00); however, no significant difference was determined at positions -602 G>A or -4 A>G (p > 0.05). CONCLUSIONS: The FCN2 c.772G>T genotype appears to be associated with predisposition to chronic adenotonsillitis in the pediatric age group. This nucleotide change is likely to influence the level of gene expression and contribute to the development of disease. PMID- 27368435 TI - Clinical characteristics of pediatric external auditory canal cholesteatoma. AB - BACKGROUND & OBJECTIVE: External auditory canal cholesteatoma (EACC) is caused by an invasion of squamous tissue into a localized area of periosteitis in the bony canal wall. The clinical characteristics of pediatric EACC are still unknown because of its rare occurrence. To date, only a single paper has reported that pediatric EACC has a less aggressive growth pattern compared to adult EACC. Further studies are required to understand the clinical behavior of EACC, i.e., its aggressiveness. The purpose of this study was to evaluate the clinical characteristics of pediatric EACC. MATERIALS AND METHODS: The clinical records of all patients diagnosed with EACC in our department from January 1, 2012 to February 29, 2016 were retrospectively reviewed, focusing on the extension of bone erosion, symptoms, and clinical findings. RESULTS: Seven patients had primary pediatric EACC (age range, 5-17 years). All patients showed unilateral EACC. Otalgia and intermittent otorrhea were common symptoms. Bacterial cultures were performed for four patients with otorrhea, which was controlled by diluted vinegar irrigation with a topical antibiotic solution. The most common bone destruction sites were the inferior and posterior walls. All patients required surgical treatment. Four patients (patient nos. 1, 3, 4, and 5) were treated via a postauricular transcanal approach. Three patients (patient nos. 2, 6, and 7) required mastoidectomy. CONCLUSION: Pediatric EACC is not less aggressive than adult EACC. Therefore, early diagnosis and adequate treatment are necessary. Further studies are required to elucidate the clinical features of pediatric spontaneous EACC. PMID- 27368436 TI - Vibratory onset and offset times in children: A laryngeal imaging study. AB - OBJECTIVES: The aim of the study was to evaluate the differences in vibratory onset and offset times across age (adult males, adult females, and children) and waveform types (total glottal area waveform, left glottal area waveform, and right glottal area waveform) using high-speed videoendoscopy. METHODS: In this prospective study, vibratory onset and offset times were evaluated in a total of 86 participants. Forty-three children (23 girls, 18 boys) between 5 and 11 years and 43 gender matched vocally normal young adults (23 females and 18 males) in the age range (21-45 years) were recruited. Vibratory onset and offset times were calculated in milliseconds from the total, left, and right Glottal Area Waveform (GAW). A two-factor analysis of variance was used to compare the means among the subject groups (children, adult male, and adult female) and waveform type (total GAW, left GAW, right GAW) for onset and offset variables. Post hoc analyses were performed using the Fishers Least Significant Different test with Bonferroni correction for multiple comparisons. RESULTS: Children exhibited significantly shorter vibratory onset and offset times compared to adult males and females. Differences in vibratory onset and offset times were not statistically significant between adult males and females. Across all waveform types (i.e. total GAW, left GAW, and right GAW), no statistical significance was observed among the subject groups. CONCLUSION: This is the first study reporting vibratory onset and offset times in the pediatric population. The study findings lay the foundation for the development of a large age- and gender-based database of the pediatric population to aid the study of the effects of maturation of vocal fold vibration in adulthood. The findings from this study may also provide the basis for evaluating the impact of numerous lesions on tissue pliability, and thereby has potential utility for the clinical differentiation of various lesions. PMID- 27368437 TI - Treatment outcomes of supraglottoplasty for pediatric obstructive sleep apnea: A meta-analysis. AB - OBJECTIVE: To comprehensively review changes in sleep parameters and the success rate of supraglottoplasty for treating obstructive sleep apnea (OSA) in children. In particular, to elucidate treatment modalities and factors affecting treatment outcomes in children with both laryngomalacia and OSA. METHODS: The study protocol was registered on PROSPERO (CRD42015027053). Two authors independently searched databases including PubMed, MEDLINE, EMBASE, and the Cochrane Review database. The keywords were "supraglottoplasty," "laryngomalacia," "OSA," "polysomnography," "child," and "humans." Supraglottoplasty served as the primary treatment for OSA or secondary treatment for persistent disease after previous surgeries. Subgroup analyses were conducted for children receiving supraglottoplasty as the primary or secondary treatment for OSA, and for children with and without comorbidities. RESULTS: Eleven studies with 121 patients were analyzed (mean age: 3.7 years; 64% boys; mean sample size: 11 patients). After surgery, the mean differences between the pre- and postoperative measurements were a significant reduction of 8.9 events/h in the apnea-hypopnea index (AHI) and an increase of 3.7% in minimum oxygen saturation (MinSaO2; P < 0.05). The overall success rate was 28% according to a postoperative AHI <1 and 72% according to an AHI <5. Children receiving supraglottoplasty as the primary treatment had significantly younger ages (0.6 vs 6.4 years P < 0.001) than those receiving supraglottoplasty as the secondary treatment, but the outcomes were similar (33% vs 19% for a postoperative AHI < 1, P = 0.27; 77% vs 61% for a postoperative AHI < 5, P = 0.233). Moreover, children with comorbidities, compared with those without, had a similar success rate according to a postoperative AHI <1 (25% vs 21%, P = 0.805) and postoperative AHI <5 (62% vs 84%, P = 0.166). CONCLUSIONS: Supraglottoplasty is an effective surgery for AHI reduction and MinSaO2 increase in children with OSA and laryngomalacia. However, complete resolution of OSA is not achieved in most cases, and factors affecting treatment outcomes in these children require future studies. PMID- 27368438 TI - A novel biallelic splice site mutation of TECTA causes moderate to severe hearing impairment in an Algerian family. AB - Congenital deafness is certainly one of the most common monogenic diseases in humans, but it is also one of the most genetically heterogeneous, which makes molecular diagnosis challenging in most cases. Whole-exome sequencing in two out of three Algerian siblings affected by recessively-inherited, moderate to severe sensorineural deafness allowed us to identify a novel splice donor site mutation (c.5272+1G > A) in the gene encoding alpha-tectorin, a major component of the cochlear tectorial membrane. The mutation was present at the homozygous state in the three affected siblings, and at the heterozygous state in their unaffected, consanguineous parents. To our knowledge, this is the first reported TECTA mutation leading to the DFNB21 form of hearing impairment among Maghrebian individuals suffering from congenital hearing impairment, which further illustrates the diversity of the genes involved in congenital deafness in the Maghreb. PMID- 27368439 TI - The effect of the leukotriene antagonist pranlukast on pediatric acute otitis media. AB - OBJECTIVE: Conventional treatment for acute otitis media mainly targets bacteria with antibiotics, neglecting to control for mediators of inflammation. Mediators of inflammation, such as leukotrienes, have been identified in patients with acute otitis media (AOM) or subsequent secretory otitis media (SOM). They can cause functional eustachian tube dysfunction or increase mucous in the middle ear, causing persistent SOM following AOM. The objective of the present study was to evaluate whether or not administration of pranlukast, a widely used leukotriene C4, D4, and E4 antagonist, together with antibiotics could inhibit the progression to SOM. METHODS: Children with AOM, who were from two to 12 years old, were randomly divided into two groups as follows: a control group in which 50 patients received antibiotic-based conventional treatment according to guidelines for treating AOM proposed by the Japan Otological Society (version 2006); and a pranlukast group, in which 52 patients were administered pranlukast for up to 28 days as well as given conventional treatment. Cases were regarded as persistent SOM when a tympanogram was type B or C2 four weeks after treatment was initiated. RESULTS: Two patients in the pranlukast group and 3 patients in the control group were excluded because they relapsed AOM within 28 days after initial treatment. Therefore, the analysis included 50 and 47 subjects in the pranlukast and control groups, respectively. The percentage of patients diagnosed with persistent SOM (22.0%) was significantly smaller in the pranlukast group compared with the control group (44.7%) (p = 0.018, chi-squared test). CONCLUSION: The results indicate that combined treatment of AOM with antibiotics and a leukotriene antagonist to control inflammation is useful for preventing progression to persistent SOM. PMID- 27368440 TI - Shared decision-making in pediatric otolaryngology: Parent, physician and observational perspectives. AB - OBJECTIVE: To describe physician and parent behavior during pediatric otolaryngology surgical consultations, and to assess whether perceptions of shared decision-making and observed behavior are related. METHODS: Parents of 126 children less than 6-years of age who underwent consultation for adeontonsillectomy or tympanostomy tube insertion were prospectively enrolled. Parents completed the Shared Decision-Making Questionnaire-Patient version (SDM-Q 9), while surgeons completed the Shared Decision-Making Questionnaire-Physician version (SDM-Q-Doc) after the consultation. Visits were video-recorded and analyzed using the Roter Interaction Analysis System to quantify physician and parent involvement during the consultation. RESULTS: Perceptions of shared decision-making between parents (SDM-Q-9) and physicians (SDM-Q-Doc) were significantly positively correlated (p = 0.03). However, there was no correlation between parents' perceptions of shared decision-making and observations of physician and parent behavior/involvement (proportion of physician socioemotional talk, task-focused talk, or proportion of parent talk). Surgeons' perceptions of shared decision-making were correlated with physician task-focused talk and proportion of parent talk. CONCLUSIONS: Parents and physicians had similar perceptions of the degree of shared decision-making to be taking place during pediatric otolaryngology consultations. However, there was variability in the degree to which parents participated, and parent perceptions of shared decision making were not correlated with actual observed involvement. PMID- 27368441 TI - Pediatric sialoblastoma: Evaluation and management. AB - OBJECTIVES: Sialoblastoma is a rare congenital salivary gland tumor of epithelial origin. The objectives of this study are to review the literature regarding clinical presentation of sialoblastoma, evaluate the effectiveness of various treatment methods, and present guidelines for evaluation and management in the pediatric population. DATA SOURCES: Case presentation and literature review. REVIEW METHODS: A comprehensive search was conducted to identify cases of pediatric sialoblastoma in the English-language literature. The presentation, evaluation, and management of reported cases were analyzed. We also report an invasive and recurrent case in a pediatric patient to highlight the aggressive nature of these lesions. RESULTS: Sixty-two cases of pediatric sialoblastoma were reviewed. The age at initial presentation ranged from before birth to 15 years. The parotid gland was the most common location (n = 47). Surgical excision was the primary treatment in all patients. Nine patients developed metastatic disease of the lung, lymph nodes, or bone. Almost a third of patients had recurrence and over two thirds of patients were tumor-free for at least 1 year following their last treatment intervention. CONCLUSION: Prompt and complete surgical excision should be recommended to prevent local and systemic recurrence of pediatric sialoblastoma. Chemotherapy has also shown promise in several cases, and clinical genomics may shed light on more therapy options. Patients should be closely followed for at least 12 months following diagnosis, or longer depending on the histopathological staging of the tumor. PMID- 27368442 TI - Pediatric adenotonsillectomy and postoperative hemorrhage: Demographic and geographic variation in the US. AB - OBJECTIVE: To examine demographic and regional variations in pediatric tonsillectomy, with or without adenoidectomy, and post-tonsillectomy hemorrhage on a national level. METHODS: The MarketScan((r)) database was analyzed for claims made between 2008-2012 for the 30 days following tonsillectomy/adenotonsillectomy in privately insured children 1-17 years of age. RESULTS: We analyzed 305,860 patients with 98.6% of these tonsillectomies occurring in an ambulatory setting. Children between 3-6 years old comprised our largest group of tonsillectomies (45.1%). More tonsillectomies were done in the South (42.1%) than any other region in our sample. Patients between 11 and17 years old had the highest percentage of bleeding (4.8%). Patients between 1 and 3 years old had the lowest values. Of the 8,518 children who presented with post operative hemorrhage, 71.7% had only one hemorrhagic event, 28.3% had at least a second one, 6.0% had at least 3 events, and 1.3% had at least 4 events. Post operative dehydration had a similar pattern. The South had the lowest percentage of post-tonsillectomy bleeds (2.5%) and overall ER visits (7.1%), both of which were most common in the Midwest. Gender had no significant association with incidence of tonsillectomy procedures or post-op complications. CONCLUSION: There are geographic and demographic variations in adenotonsillectomy and in post operative complications for children nationally. PMID- 27368443 TI - Cerumen: A fundamental but neglected problem by pediatricians. AB - OBJECTIVES: Under physiological conditions, cerumen (Ce) is regularly extruded from the ear canal by a self-cleaning mechanism. Failure of this mechanism leads to excessive accumulation or impaction of Ce. Limited data are available concerning the prevalence of cerumen in healthy and sick infants and children. We assessed the prevalence of Ce in a large population of infants and children and compared the Ce removal attitudes of paediatricians (PEDs) and otorhinolaryngologists (ENTs). METHODS: Children seen in November 2014 for acute respiratory infections, including suspected acute otitis media, or well-being visits, were enrolled. The following data were recorded: presence, laterality, and amount of Ce; presenting complaints and final diagnosis; attempt to remove Ce during the visit; and type of physician. RESULTS: Among 819 children aged 1 month to 12 years, Ce was present in 594 (72.5%), of whom 478 (80.5%) had bilateral Ce, and 261 (43.9%) had Ce in a relevant amount (cerumen obstructing at least 50% of the ear canal). Presence of Ce was more common in younger and in African or Asian children. PEDs were less likely to remove cerumen than ENTs (28.8% vs 91.0%, p < 0.001) irrespective of age, gender, race and reason for visit. Ce was removed by PEDs in less than one-third of sick children with a final diagnosis of acute otitis media (AOM) (31.6%) compared with almost all the children by ENTs (95.6%, p < 0.001). CONCLUSION: Ce is highly prevalent in healthy and sick children but is quite neglected by PEDs. Educational programs to reinforce the importance of Ce removal and to improve the techniques for removal in case of suspected AOM should be implemented and rigorously evaluated in order to avoid incorrect diagnosis and erroneous treatments. PMID- 27368444 TI - Pediatric adenoid surgery in Sweden 2004-2013: Incidence, indications and concomitant surgical procedures. AB - OBJECTIVES: To describe the incidence and indications of adenoid surgery and concomitantly performed ENT surgical procedures in a nationwide cohort covering several years of practice. METHODS: A retrospective study based on data from the National patient registry in Sweden. All children born from 1st of January 2004 to December 31st, 2013 who underwent adenoidectomy for the first time in Sweden during 2004-2013 were included in the study. Patient characteristics (age and gender), indications for surgery and performed ENT surgery were evaluated. RESULTS: 40,829 children underwent adenoid surgery during the studied period. Of these, 24,537 (60%) were boys. Mean and median age at surgery in the studied population was 4 years and 3.5 years respectively for both boys and girls. The most frequently performed surgical procedure was adenotonsillar surgery 43% (n = 17,434) followed by solitary adenoid surgery 26% (n = 10,749). The most frequent registered indication was hypertrophy 60% (n = 24,422) followed by hypertrophy and otitis media 21% (n = 8425). The highest age related incidence for all types of adenoid surgery taken together was 2-4 years of age for both genders. Boys had higher incidence rates than girls for all ages and all types of surgery except at eight years of age. CONCLUSIONS: The main findings were that adenoidectomy most commonly was performed together with surgery of the tonsils on the indication hypertrophy, that adenoid- and adenoid related ENT surgery were most commonly performed between 2 and 5 years of age and that the incidence in surgical rates was higher for boys than girls. There seem to be large unwarranted variations between countries regarding incidence rates and we believe that there is a need for further studies in order to establish recommendations for best practice regarding adenoid and related ENT surgeries. PMID- 27368445 TI - Pediatric lymphedema caused by diffuse cervical lymphadenopathy: A case report and review of the literature. AB - Pediatric head and neck lymphedema is rare and there have not been any reported cases in children. Here we discuss severe, diffuse head and neck lymphedema in a child caused by compression of the internal jugular veins by lymphadenopathy from Kawasaki's disease. With steroid and intravenous immunoglobulin treatment, the lymphadenopathy improved and facial edema slowly resolved. In review of the literature, complications of head and neck lymphedema including airway obstruction and blindness are discussed. This case highlights the importance of the pediatric otolaryngologist considering lymphedema as a cause for facial swelling and monitoring for complications of lymphedema. PMID- 27368446 TI - Treatment outcome after neonatal cleft lip repair in 5-year-old children with unilateral cleft lip and palate. AB - INTRODUCTION: The aim of this study was to assess speech outcomes and dental arch relationship of 5-year-old Czech patients with unilateral cleft lip and palate (UCLP) who have undergone neonatal cleft lip repair and one-stage palatal closure. METHODS AND MATERIALS: Twenty-three patients with UCLP, born between 2009 and 2010, were included in the study. Three universal speech parameters (hypernasality, articulation and speech intelligibility) have been devised for speech recordings evaluation. Outcomes of dental arch relationship were evaluated by applying the GOSLON Yardstick and subsequently compared with the GOSLON outcome of other cleft centers. RESULTS: Moderate hypernasality was present in most cases, the mean value for articulation and speech intelligibility was 2.07 and 1.93, respectively. The Kappa values for inter-examiner agreement for all the three speech outcomes ranged from 0.786 to 0.808. Sixty-three percent of patients were scored GOSLON 1 and 2, 26% GOSLON 3, and 10% GOSLON 4. GOSLON mean score was 2.35. Interrater agreement was very good, represented by kappa value of 0.867. CONCLUSION: The treatment protocol, involving neonatal cleft lip repair and one stage palatal repair performed up to the first year of UCLP patient's life, has shown good speech outcomes and produced very good treatment results in regard to maxillary growth, comparable with other cleft centers. PMID- 27368447 TI - A chilling reminder: Pediatric facial trauma from recreational winter activities. AB - BACKGROUND: Winter activities offer children and adolescents an outdoor recreational opportunity during the coldest months. Our objectives were to estimate the national incidence of facial injury associated with recreational winter activities. Furthermore, we analyze demographic trends and clinical characteristics of patients presenting to emergency departments (EDs). METHODS: The National Electronic Injury Surveillance System (NEISS), a population-based resource, was evaluated for ED visits from 2010 to 2014 for children injured from "active" winter -undertakings (snowboarding, skiing, ice skating) and sledding/tubing. Entry narratives were evaluated for demographics, diagnoses, and other clinical factors. RESULTS: 841 entries amounting to an estimated 27,618 patients were evaluated. The most common injuries were lacerations (69.4%), contusions/abrasions (19.5%), and fractures (5.5%), with the most common fracture sites being the nose (60.9%), orbit (15.2%), and mandible (10.9%). Median age was 9 years (IQR 5-12), and 65.8% were male. A greater proportion of adolescents sustained fractures than younger children (8.1% vs. 4.0%). The majority of fractures were to the nose. CONCLUSION: With nearly 30,000 ED visits over five years, participation in winter sports can be perilous. Adolescents harbor a greater risk of sustaining serious injuries than younger children, and patients injured sledding/tubing had a greater fracture risk compared to those participating in more "active" winter activities. As upper/mid-face fractures occurred in only 1.4%, these findings reinforce a very limited role for CT. These findings suggest a need for greater use of facial protection and closer supervision of older children participating in these activities. PMID- 27368448 TI - Emergent airway management in the labor and delivery suite. AB - INTRODUCTION: Congenital airway obstruction is of varied etiology and uncommonly encountered. Prenatal care and imaging have enhanced detection of these abnormalities and allow for multi-disciplinary care planning for airway management at delivery. Despite the availability and advances in prenatal imaging, unanticipated airway obstruction may not be identified until the time of delivery. METHODS: Case series. RESULTS: Four airway emergencies were encountered in the labor and delivery suite over an eight-month period. Clinical history is correlated with autopsy findings. Congenital upper airway and laryngotracheal anomalies are reviewed. Recommendations to improve timely and efficient airway management in the labor and delivery suite are discussed and a protocol for a multi-disciplinary neonatal emergency airway response team is offered for consideration. CONCLUSIONS: The development and implementation of a multi disciplinary emergency newborn airway protocol is both realistic and feasible. While it did not improve survivability in our small group, it did reduce response time. It, or a protocol like it, is recommended for institutions caring for high risk pregnancies and with Neonatal Intensive Care Units with high acuity patients. PMID- 27368450 TI - Avoiding surgical pitfalls during resection of a "hybrid" first and second branchial cleft cyst - A case report. PMID- 27368449 TI - Supraglottoplasty outcomes in children with Down syndrome. AB - OBJECTIVE: Children with Down syndrome have a higher incidence of upper airway obstruction and laryngomalacia. We sought to determine outcomes of supraglottoplasty in this patient population. METHODS: A retrospective chart review was performed from January 2000 through January 2014. Children (n = 18) at our institution with the diagnosis of Down syndrome who underwent supraglottoplasty were included. We reviewed patient characteristics, preoperative findings, and surgical outcomes (stridor, feeding problems, respiratory distress, weight, sleep apnea, and tracheostomy or feeding tube dependence). RESULTS: The average age at surgery was 7.7 months. Operative indications included feeding difficulties (n = 9), noisy breathing or respiratory distress (or both) (n = 16), and sleep-related symptoms (n = 7). Most patients (89%) were extubated successfully on postoperative day 1. There were 2 major complications (CPAP requirement and aspiration pneumonia) and no perioperative deaths. Fifty percent had improved weight (mean = 18 percentile points). Feedback was available from 88% of parents with 100% reporting improvement in respiratory symptoms and 93% reporting improved feeding. Eight patients (44%) subsequently required either adenoidectomy or adenotonsillectomy. Two patients later underwent tracheostomy, 2 subsequently needed a gastrostomy tube and 2 required revision supraglottoplasty. CONCLUSIONS: The majority of children with Down syndrome and laryngomalacia benefit from supraglottoplasty, with outcomes of improved breathing, feeding, and sleeping. However, approximately half may require additional airway procedures. This procedure is well tolerated and associated with a low risk of complications especially given their high rate of comorbidities. PMID- 27368451 TI - Pediatric thyroid nodules: A single center experience. AB - OBJECTIVES: 1. Analyze our center's experience with thyroid nodules. 2. Evaluate the efficacy of fine needle biopsy. 3. Compare our experience with the 2015 ATA guidelines. METHODS: IRB approved retrospective chart review from July 1993-July 2014 at a tertiary pediatric institution. Patients under age 21 with documented thyroid nodules who underwent fine needle aspiration, and/or thyroidectomy were included. RESULTS: 126 patients were identified. 84.1% (n = 106) were female. Age range was 12 months-20 years. The average age was 13.3 +/- 4.1 years. The nodules ranged from 0.5 cm to 6 cm 53.9% (n = 68) had a fine needle biopsy done. 42.6% (n = 29) fine needle biopsies were benign, 26.5% (n = 18) were non-diagnostic, 13.2% (n = 9) were classified as "atypia", 0.09% (n = 6) were consistent with thyroiditis, and 0.09% (n = 6) were suspicious for papillary carcinoma. 78.6% (n = 99) underwent surgery. 7 patients with "benign" needle biopsies underwent surgery: all had follicular adenoma. 7 patients with "atypia" needle biopsies underwent surgery: one patient had papillary thyroid cancer. 8 patients with non diagnostic needle biopsies underwent surgery: one patient had papillary thyroid cancer. All the patients with needle biopsy suspicious for papillary carcinoma had papillary carcinoma on final pathology. 99 patients underwent surgery: 14.1% (n = 14) had papillary carcinoma and 2% (n = 2) had medullary carcinoma. CONCLUSION: Our review of pediatric thyroid nodules at our institution supports data previously reported. 84% of identified patients were female, supporting previous data that nodules are more prevalent in the female population. Of the 126 patients identified, 12.7% had thyroid carcinoma, supporting the 7-25% range described in previous literature. Our institution showed a high positive predictive value of FNA for papillary thyroid carcinoma. PMID- 27368452 TI - Pediatric nasal orbital cellulitis in Shenzhen (South China): Etiology, management, and outcomes. AB - OBJECTIVES: The study aimed to investigate the clinical characteristics, diagnosis, and treatment of orbital cellulitis in children in Shenzhen, China, and to improve the experience of antibiotic therapy for the treatment of orbital cellulites. METHODS: This retrospective study reviewed data from 20 children admitted to Shenzhen Children's Hospital between January 2009 and December 2013, with a diagnosis of nasal orbital cellulitis, severe enough to warrant hospitalization. Thirteen subjects (65%) were male and 7 (35%) were female. The median age was 3.5 years (2 months-7.2 years). The relationship between serum C reactive protein (CRP), white blood cell count, and length of hospitalization were analyzed. The patients were categorized into 2 groups according to treatment: Those treated with a combination of cefoperazone plus sulbactam sodium vs. those treated with other antibiotic treatment regimens. RESULTS: Levels of serum CRP (29.8 +/- 22.0 mg/L) at the time of admission were positively correlated with length of hospitalization (6.3 +/- 4.1 days, r = 0.46, P < 0.05). The length of time necessary for CRP levels to return to normal range after admission (3.4 +/- 1.8 days) was also significantly correlated length of hospitalization ((6.3 +/- 4.1)days) (r = 0.81, P < 0.01). The hospital days whose CRP can be decreased to normal within 3 days (4.3 +/- 1.7 days) after antibiotic treatment were significantly shorter than the others (9.1 +/- 5 days) (t = 2.61, P < 0.05). The length of hospitalization (4.3 +/- 1.9 days) for patients (n = 12) receiving combined cefoperazone and sulbactam sodium antibiotic treatment was significantly shorter than the length of stay (9.3 +/- 4.7 days) for those patients (n = 8) treated with other antibiotic regimens (t = 2.83, P < 0.05). Bacterial pathogens were identified in 4 patients (20%), including 3 cases of Staphylococcus aureus and 1 case of Streptococcus anginosus. Acquired methicillin resistant Staphylococcus aureus (MRSA) were found in the three pus cultures. CONCLUSION: Early efficient antibiotic treatment over the first three days may shorten the course of nasal orbital cellulitis and potentially prevent the formation of orbital abscesses. Clinical factors that were significantly related to patient recovery included improved clinical signs and normalization of blood CRP levels. Our results also indicate that combined cefoperazone and sulbactam sodium is effective and should be recommended for the treatment of pediatric orbital cellulitis. PMID- 27368453 TI - Update on local allergic rhinitis. AB - We here provide an update on the literature regarding local allergic rhinitis (LAR). In reviewing LAR, we have included an updated definition, classifications, mechanisms, comorbidities, and recommendations for diagnosis and treatment for LAR, as well as the defined research areas for future evidence-based studies. LAR is a localised nasal allergic response in the absence of systemic atopy characterised by local production of specific IgE (sIgE) antibodies, a TH2 pattern of mucosal cell infiltration during natural exposure to aeroallergens, and a positive nasal allergen provocation test response, with the release of inflammatory mediators. The localised allergic response of LAR is an important topic for the study of allergies. This review provides an update on the current knowledge of LAR. PMID- 27368454 TI - Incremental change in cross sectional area in small endotracheal tubes: A call for more size options. AB - OBJECTIVE: To elucidate the relatively large incremental percent change (IPC) in cross sectional area (CSA) in currently available small endotracheal tubes (ETTs), and to make recommendation for lesser incremental change in CSA in these smaller ETTs, in order to minimize iatrogenic airway injury. METHODS: The CSAs of a commercially available line of ETTs were calculated, and the IPC of the CSA between consecutive size ETTs was calculated and graphed. The average IPC in CSA with large ETTs was applied to calculate identical IPC in the CSA for a theoretical, smaller ETT series, and the dimensions of a new theoretical series of proposed small ETTs were defined. RESULTS: The IPC of CSA in the larger (5.0 8.0 mm inner diameter (ID)) ETTs was 17.07%, and the IPC of CSA in the smaller ETTs (2.0-4.0 mm ID) is remarkably larger (38.08%). Applying the relatively smaller IPC of CSA from larger ETTs to a theoretical sequence of small ETTs, starting with the 2.5 mm ID ETT, suggests that intermediate sizes of small ETTs (ID 2.745 mm, 3.254 mm, and 3.859 mm) should exist. CONCLUSION: We recommend manufacturers produce additional small ETT size options at the intuitive intermediate sizes of 2.75 mm, 3.25 mm, and 3.75 mm ID in order to improve airway management for infants and small children. PMID- 27368455 TI - An unusual sharp magnetic foreign body in the oesophagus and its removal: A case report. AB - Ingestion of foreign bodies is a common pediatric problem. The majority of ingested foreign bodies pass spontaneously. Oesophageal foreign bodies should be urgently removed because of their potential to cause complications. Ingested batteries that lodge in the oesophagus, sharp or pointed foreign bodies in the oesophageal or gastric tract, and ingestion of multiple magnets all require urgent endoscopic removal. A 4-year-old boy ingested a sharp magnetic foreign body, which was removed via rigid oesophagoscopy without complication. To the best of our knowledge, this is the only sharp magnetic foreign body ingested by a young child ever reported in the English-language literature. We describe the presentation and therapeutic procedure adopted in this case. PMID- 27368456 TI - Congenital midnasal stenosis - A novel technique for management. AB - Neonates are obligate nasal breathers and nasal obstruction in a neonate is an emergency. Here we report two cases of congenital mid-nasal stenosis, discuss its presentation and diagnosis with description of a novel method of management. PMID- 27368457 TI - Prevalence of 2.2 per mille of significant hearing loss at school age suggests rescreening after NHS. AB - OBJECTIVES: The study aims to determine the prevalence of different degrees of significant hearing loss in a complete sample of Austrian school-age children born between 1997 and 2001 living in the federal state of Carinthia and to evaluate the role of Newborn Hearing Screening (NHS) in the identification of later hearing loss. METHODS: In Carinthia, all school-age children with significant hearing loss (mean pure tone average in the better ear above 40 dB) are registered by the Department of Education. From five complete birth cohorts from 1997 to 2001 (n = 28.171) all the children with sensorineural hearing loss (n = 61, mean age 10.5, age range 7.5-13.6 years) were assessed for their hearing threshold and level of cognitive functioning. Socio-demographic data, including information about NHS and amplification with hearing devices, were collected from parents and teachers using structured interviews. RESULTS: 2.2 children per thousand (49.2% male) were found to be affected by significant bilateral hearing loss at school age, with 36.1% of them having a moderate hearing loss, 34.4% severe, and 29.5% profound. Fourteen children (23.0%) used cochlear implants. Their mean nonverbal IQ was 93.4 (SD 23.1), including 13.1% of children with intellectual disabilities (IQ < 70). Of those who had undergone NHS (85.2%), 50.0% had passed the screening according to parents' reports. CONCLUSIONS: A rate of significant hearing loss in school-age children was observed which was twice the rate found in newborns. Ongoing awareness of late-onset hearing loss to improve identification and hearing screening at school entry are recommended. PMID- 27368458 TI - Helicobacter pylori detection and clinical symptomatology of gastroesophageal reflux disease in pediatric patients with otitis media with effusion. AB - OBJECTIVES: The study aimed to demonstrate Helicobacter pylori presence in otitis media with effusion (OME) and its association with symptomatology of gastroesophageal reflux disease (GERD). METHODS: In a cohort study, 69 effusions were collected during tympanostomy tube insertion for H. pylori detection using PCR and ELISA. Validated questionnaires were performed according to age for clinical diagnosis of GERD; chi-square *2 statistical analysis was made. RESULTS: Eight of the 69 ear effusions (5.7%) were positive for H. pylori detection using ELISA. Two patients (2.9%) had positive results for H. pylori detection using ELISA and PCR. These eight patients had positive results too in GERD questionnaires. None of the patients with negative/suspect questionnaires had positive results for H. pylori. We found statistical association between the results of ELISA, PCR and questionnaires (*2, p = 0.001). CONCLUSIONS: The H. pylori presence in effusions varies widely, in our population the frequency was lower than other reports. We found strong association between H. pylori in effusions and positive GERD questionnaires. The bacterium role in OME chronicity is not clear, but this study supports the GERD participation in OME pathogenesis. PMID- 27368459 TI - Prevalence of hearing loss in children with 22q11.2 deletion syndrome. AB - OBJECTIVE: The purpose of this study was to determine the prevalence and characterize the types of hearing loss in pediatric patients with 22q11.2 deletion syndrome (22q11DS). METHODS: Fifty-eight patients were identified via retrospective chart review performed of patients with 22q11DS between 1996 and 2014. Patient demographics, pertinent family history, associated comorbidities, and degree and type of hearing loss were gathered for each patient. A literature review of the National Library of Medicine's database with a focus on hearing loss and 22q11DS was performed. RESULTS: 22 patients (38%) were found to have hearing impairment: 68% with conductive hearing loss, 14% with sensorineural hearing loss, and 18% with mixed hearing loss. Patients with hearing loss regardless of type had a higher prevalence of developmental delay (55%), cleft palate (23%), articulation disorders (77%), and a greater need for tympanostomy tubes (73%) compared to patients with normal hearing. Temporal bone computed tomography scans of 5 patients revealed a variety of abnormalities in the middle and/or inner ears. CONCLUSION: Hearing impairment occurs in up to 38% of 22q11DS patients of both conductive and sensorineural types, with the conductive type being the most common. These patients have a greater need for tympanostomy tubes and a higher prevalence of developmental delay and speech articulation disorders. Early hearing screening and treatment is warranted in this population. PMID- 27368460 TI - Management of paediatric periorbital cellulitis: Our experience of 243 children managed according to a standardised protocol 2012-2015. AB - INTRODUCTION: Paediatric periorbital cellulitis is a common condition. Accurate assessment can be challenging and appropriate use of CT imaging is essential. We audited admissions to our unit over a four year period, with reference to CT scanning and adherence to our protocol. METHODS: Retrospective audit of paediatric patients admitted with periorbital cellulitis, 2012-2015. RESULTS: Total of 243 patients included, mean age 4.7 years with slight male predominance, the median length of admission was 2 days. 48/243 (20%) underwent CT during admission, 25 (52%) of these underwent surgical drainage. As per protocol, CT brain performed with all orbital scans; no positive intracranial findings on any initial scan. Three children developed intracranial complications subsequently; all treated with antibiotics. Our re-admission rate within 30 days was 2.5%. CONCLUSIONS: Our audit demonstrates benefit of standardising practice and the low CT rate, with high percentage taken to theatre and no missed abscesses, supports the protocol. There may be an argument to avoid CT brain routinely in all initial imaging sequences in those children without neurological signs or symptoms. PMID- 27368461 TI - Evaluation of cochlear functions in children with Familial Mediterranean Fever. AB - OBJECTIVES: To evaluate cochlear functions in patients with Familial Mediterranean Fever in relation to the disease severity score and treatment duration. METHODS: 50 patients (4-18 years) who had been followed-up with the diagnosis of FMF and regularly receiving appropriate colchicine treatment and 39 healthy controls were included in the study. All the patients and controls were evaluated by audiologic evaluation, including high-frequency pure-tone audiometry and distortion product otoacoustic emission tests (DPOAE). The disease severity was determined by scoring system developed by Pras et al. RESULTS: Fifty patients (52% female, 48% male; mean age12.2 +/- 4.1 years) and 39 controls (58.9% female, 41.1% male, mean age 11.1 +/- 3.4 years) were enrolled the study. The pure tone average of FMF patients was significantly higher than that of the control group at 500, 4000, and 8000 Hz frequencies. The patients' DPOAE signal values at 6 kHz, 8 kHz frequencies and SNR values at 8 kHz were significantly higher than control group. The patients' audiometry and DPOAE results were compared with the disease severity scores. Pure tone average was significantly higher in severe and moderate patient groups compared to the mild patient group at 2000 Hz frequency. DPOAE signal values showed statistically significant differences between the patient severity scores at 1.4 and 2.8 kHz frequencies. The mean colchicine treatment duration was found to be 5.1 +/- 3.7 years. There were significant differences at 250 and 500 Hz frequencies when patients' audiometry results were compared with the treatment periods. CONCLUSIONS: FMF affects cochlear functions particularly at high frequencies. PMID- 27368462 TI - Neutrophil to lymphocyte ratio in Bell's palsy. PMID- 27368463 TI - Indications of pediatric tracheostomy over the last 30 years: Has anything changed? AB - IMPORTANCE: Recent reports have shown that the indications for pediatric tracheostomy have evolved over time. OBJECTIVE: To review the indications for pediatric tracheostomy over the last 30 years. DESIGN: Retrospective chart review. SETTING: Tertiary referral children's hospital. PARTICIPANTS: Patients who underwent tracheostomy. INTERVENTION: Surgical tracheostomy placement. MAIN OUTCOMES AND MEASURES: Medical records for patients who underwent surgical tracheostomy over the 30-year study period (1984-2014) were reviewed. Patient characteristics including age, gender, birth-weight, gestational age and death were collected and compared with the primary indication for tracheostomy using bivariable analysis. RESULTS: Five hundred and one patients met inclusion criteria. The most common primary indications for tracheostomy were cardiopulmonary disease (34%) and neurological impairment (32%), followed by airway obstruction (19%), craniofacial (11%), and traumatic injury (4%). Over the last five years (2010-14) cardiopulmonary disease became the most common indication for tracheostomy. CONCLUSIONS: and RELEVANCE: The indications for pediatric tracheostomy have evolved over the past 30 years. Infectious causes of airway obstruction and tracheostomy have almost disappeared. Tracheostomy is now most commonly performed in very premature patients with cardiopulmonary or neurological impairment who require prolonged ventilator support. PMID- 27368464 TI - Balance disorders in childhood: Main etiologies according to age. Usefulness of the video head impulse test. AB - Balance disorders are common in adult patients but less usual in the pediatric population. When this symptomatology appears in children it is a cause for concern, both for parents and health-care professionals. OBJECTIVES: To explain the balance disorders in children describing a case series and to discuss the main etiologies found according to age. STUDY DESIGN: A retrospective, observational, descriptive, and cross-sectional study was conducted. POPULATION: Patients aged 1-18 years who consulted because of balance disorders at the otolaryngology department of a pediatric tertiary-care hospital between March 2012 and July 2015. RESULTS: Two hundred and six patients were included in the study. Median age was 10 years. The most common diagnoses were vestibular migraine in 21.8% of the children, ataxia in 9.22%, benign paroxysmal vertigo of childhood in 7.77%, and post-traumatic vertigo in 6.31%.Overall, 61 videonystagmographies- of which 46 were normal - and 55 video head impulse tests which were normal in 45 and showed abnormalities in the vestibulo-ocular reflex gain in 10 - were performed. CONCLUSIONS: In a child with balance disorders, the medical history and neurotological examination are essential. Vestibular migraine is the most commonly found disorder in every age group, and most of the patients have a family history of migraine. Ancillary studies, especially the video head impulse test, provide important data to confirm the diagnosis. PMID- 27368465 TI - Danish guidelines on management of otitis media in preschool children. AB - INTRODUCTION: Otitis media is one of the most common diseases in small children. This underlines the importance of optimizing diagnostics and treatment of the condition. Recent literature points toward a stricter approach to diagnosing acute otitis media (AOM). Moreover, ventilating tube treatment for recurrent AOM (RAOM) and chronic otitis media with effusion (COME) has become the most frequently performed surgical procedure in pre-school children. Therefore, the Danish Health and Medicines Authority and the Danish Society of Otorhinolaryngology, Head and Neck Surgery deemed it necessary to update the Danish guidelines regarding the diagnostic criteria for acute otitis media and surgical treatment of RAOM and COME. METHODS: The GRADE system (The Grading of Recommendations Assessment, Development and Evaluation) was used in order to comply with current standards of evidence assessment in formulation of recommendations. An extensive literature search was conducted between July and December 2014. The quality of the existing literature was assessed using AGREE II (Appraisal of Guidelines for Research & Evaluation), AMSTAR (assessing the Methodological Quality of Systematic Reviews), QUADAS-2 (Quality of Diagnostic Accuracy Studies), Cochrane Risk of Bias Tool for randomized trials and ACROBAT NRSI (A Cochrane Risk of Bias Assessment Tool for Non-Randomized Studies). The working group consisted of otolaryngologists, general practitioners, pediatricians, microbiologists and epidemiologists. CONCLUSION: Recommendations for AOM diagnosis, surgical management for RAOM and COME, including the role of adenoidectomy and treatment of ventilating tube otorrhea, are proposed in the guideline. PMID- 27368466 TI - Wideband reflectance in Down syndrome. AB - OBJECTIVE: Children with Down syndrome (DS) have a high incidence of middle ear disorders and congenital abnormalities of the external, middle and inner ear. Energy reflectance (ER), a wideband acoustic immittance (WAI) measurement parameter, can measure the sound energy reflected or absorbed in the ear canal over a wider range of frequencies more efficiently and faster than conventional single-tone 226 Hz tympanometry. The aim of the present study was to compare the WAI measurements of children with DS with those of typically developing, normal hearing children according to their tympanometric findings. METHODS: Four groups of children with Down syndrome (age range: 2 years and 4 months to 16 years and 3 months; mean age: 8.5 yr) with normal tympanograms (19 ears), flat tympanograms (13 ears), mild negative pressure tympanograms (6 ears between -100 and -199 daPa at the admittance peak) and severe negative pressure tympanograms (4 ears at -200 daPa or lower at the admittance peak) were assessed. All findings were compared with data obtained from 21 ears of a healthy control group (age range: 3 years and 1 month to 13 years and 11 months; mean age: 7.9 yr). The subjects underwent tympanometry with a 226-Hz probe tone frequency and ER measurements along the 200 6,000 Hz range with a chirp stimulus using the Middle-Ear Power Analyzer (MEPA3 - HearID) by Mimosa Acoustics (Champaign, IL), software, version 3.3 [38]. RESULTS: Statistically significant differences were observed in the ER curves for some comparisons between the studied groups. There was also a negative correlation between the static acoustic admittance at the tympanic membrane level and ER measured with a chirp stimulus at 500 and 1,000 Hz. The discriminant analysis technique, which used a chirp stimulus at 1,000 and 1,600 Hz to classify the participants' data based on ER values, achieved a correct classification rate of 59.52% for participants with DS. CONCLUSION: While groups with abnormal middle ear status, as indicated by tympanometry, showed higher ER values compared to the DS tymp A group and the control group, similar reflectance curves were observed between control group and the DS tymp A group. WAI shows promise as a clinical diagnostic tool in investigating the impact of middle ear disorders in DS group. However, further research is required to investigate this issue in narrower age range group and a larger sample size. PMID- 27368467 TI - Video head-impulse test (vHIT) in dizzy children with normal caloric responses. AB - OBJECTIVE: The caloric test and the video head-impulse test are diagnostic tools to examine dizzy patients through assessing the function of the semicircular canals. There are major differences between the two tests as regards stimulus characteristics, methodology, and function examined. The aim of this study is to evaluate the results of vHIT in children and adolescents with normal caloric test. MATERIALS AND METHODS: This work was performed on 63 patients, but 14 were excluded because of technical problems in the caloric test. So, this is a prospective work in 49 patients (27 females and 22 males) with different types of vestibular disease seen because of vertigo in which both procedures were performed the same day. The caloric test was performed with air at two different temperatures in which both ears were irrigated alternately. Then, the video head impulse test was carried out. Main outcome measures were the gain of vestibulo ocular reflex, gain asymmetry, and refixation saccades in the vHIT. RESULTS: in all studied cases, caloric test was normal. The mean age of patients was 16 years. By vHIT, in 8 patients (16%) no abnormality was detected, while abnormal findings were found in 41 patients. Single canal affection was seen in 29 patients whereas 12 patients had combined canal affection. The right side was affected in 27 and left side in 22 patients. In single canal affection, isolated horizontal canals were affected in 4, anterior canals in 5 and posterior canals in 20 patients. While in combined canal affection, the affection is seen in the same ear. Moreover the most common pattern seen is affection of left anterior and left posterior canals. CONCLUSION: The caloric and vHIT is very important tests in diagnosis of dizzy patients. The information from both methods is redundant in some cases but complementary in most. vHIT is a "child friendly," relatively easy to-use, and simple tool to evaluate each of the 6 semicircular canals. PMID- 27368468 TI - Protective effect of a purified polyphenolic extract from Ecklonia cava against noise-induced hearing loss: Prevention of temporary threshold shift. AB - OBJECTIVE: Noise is one of the most common causes of hearing loss. Approximately 16% of American teenagers (12-19 years) have hearing loss caused by loud noise. The implication of noise-induced hearing loss (NIHL) in teenagers has received increasing attention. Although temporary threshold shift (TTS), a type of NIHL, is a transient hearing loss, it can accelerate age-related hearing loss. Reactive oxygen species are a primary cause of TTS. As the polyphenols from Ecklonia cava are known to have potent antioxidant effects, we investigated the protective effects of a purified polyphenolic extract of Ecklonia cava (PPEE) against TTS in mice. METHODS: The radical-scavenging activity of PPEE was evaluated using the 1,1-diphenyl-2-picrylhydrazyl assay. The PPEE + Noise and Saline + Noise groups were administered intraperitoneal PPEE (100 mg/kg) and saline, respectively, for 5 days before exposure to noise at 100 dB SPL for 60 min. Hearing ability was assessed following noise exposure using auditory brainstem responses and distortion product otoacoustic emissions. RESULTS: PPEE exhibited significant radical scavenging activity. The ABR threshold shifts 1 day after exposure to noise at 16 kHz and 1, 7, and 14 days after exposure to noise at 32 kHz, were significantly less in the PPEE + Noise than in the Saline + Noise group. One day after noise exposure, mice in the PPEE + Noise group showed a significant degree of protection in relation to their DPOAE level at f2, 17, and 28 kHz. CONCLUSIONS: These findings suggest that PPEE may be a potential preventive agent against TTS. In addition, as a food ingredient approved by the United States Food and Drug Administration, PPEE may be administered to those who are exposed to noise inevitably with little likelihood of adverse effects, thereby contributing to the prevention of TTS. PMID- 27368469 TI - Long-term outcomes of a transmastoid lateral semicircular canal approach to congenital CSF otorrhea in children associated with recurrent meningitis and severe inner ear malformation. AB - OBJECTIVE: To investigate the long-term effectiveness of transmastoid lateral semicircular canal approach (TMLSCCA) to repair cerebrospinal fluid (CSF) leakage in children associated with recurrent meningitis and severe congenital inner malformation. METHOD: A retrospective study was conducted in a university hospital, academic medical center. Fifteen children with recurrent meningitis, secondary to severe congenital inner ear malformation, were included in the study. All of them had CSF associated otorrhea and treated using TLSCCA to repair CSF otorrhea by packing the vestibule with muscle and fascia. Observation of the status of postoperative CSF leakage, recurrence of meningitis and complication were conducted. RESULTS: None of the cases had recurrent meningitis and CSF leakage after their TLSCCA procedure in the follow-up period of 1-8.5 years. One case presented with transient facial nerve paralysis and completely recovered 3 months later. CONCLUSION: TLSCCA for CSF otorrhea in children with recurrent meningitis secondary to congenital inner ear malformation is an alternative approach that offers some advantages. PMID- 27368470 TI - Obstructive sleep apnea in obese children and adolescents, treatment methods and outcome of treatment - A systematic review. AB - OBJECTIVES: To systematically review and discuss the outcome of treating obstructive sleep apnea (OSA) in obese children and adolescents. METHODS: In February 2016 Pub Med was searched using a predetermined string to retrieve all relevant articles. The search identified 518 publications. In total 16 articles were included for review using the selected inclusion and exclusion criteria. The PRISMA guidelines was used. RESULTS: OSA was significantly more likely to persist in obese children after adenotonsillectomy. The prevalence of persistent OSA ranged from 33 to 76% in obese children and from 15 to 37% in non-obese children depending on the definition of OSA, the degree of obesity and the age of the study population. The few studies that investigated the effect of weight loss found that OSA improved significantly after intervention and that the prevalence of persistent OSA varied between 10 and 38%. Positive airway pressure was effective for treating OSA, but the mean nightly use was <4 h in two out of three available studies. CONCLUSION: Obese children benefit less from adenotonsillectomy than normal-weight children. Weight loss improve OSA significantly, but more research is needed to clarify the role of weight loss as treatment for OSA. Positive airway pressure is effective for treating OSA; however, adherence is a challenge. PMID- 27368471 TI - Identifying predictive factors for long-term complications following button battery impactions: A case series and literature review. AB - OBJECTIVES: To complement a case series review of button battery impactions managed at our single military tertiary care center with a thorough literature review of laboratory research and clinical cases to develop a protocol to optimize patient care. Specifically, to identify predictive factors of long-term complications which can be used by the pediatric otolaryngologist to guide patient management after button battery impactions. METHODS: A retrospective review of the Department of Defense's electronic medical record systems was conducted to identify patients with button battery ingestions and then characterize their treatment course. A thorough literature review complemented the lessons learned to identify potentially predictive clinical measures for long term complications. RESULTS: Eight patients were identified as being treated for button battery impaction in the aerodigestive tract with two sustaining long-term complications. The median age of the patients treated was 33 months old and the median estimated time of impaction in the aerodigestive tract prior to removal was 10.5 h. Time of impaction, anatomic direction of the battery's negative pole, and identifying specific battery parameters were identified as factors that may be employed to predict sequelae. CONCLUSION: Based on case reviews, advancements in battery manufacturing, and laboratory research, there are distinct clinical factors that should be assessed at the time of initial therapy to guide follow-up management to minimize potential catastrophic sequelae of button battery ingestion. PMID- 27368472 TI - Improvement in hearing loss over time in Cornelia de Lange syndrome. AB - OBJECTIVES: Patients with Cornelia de Lange Syndrome (CdLS) are reported to have conductive (CHL) and sensorineural hearing loss (SNHL), but there is little information pertaining to the progression of hearing loss over time. The goal of this study was to examine the prevalence of CHL and SNHL in adults and children with CdLS and look for changes in SNHL over time. METHODS: Retrospective chart review of patients with CdLS presenting to a CdLS clinic was conducted. Also, a written survey of clinical concerns was collected from additional patients/families seen in the clinic and through the Cornelia de Lange Foundation. RESULTS: Seventy-eight patients (50% female) were included in the chart review. Mean age was 16.8 +/- 11.4 years (range-0.6-50 years) and mean age at diagnosis of hearing loss was 4.6 +/- 10.6 years (n = 26). Five patients (6.4%) had severe to profound SNHL that improved with time, including 2 who had complete normalization of audiogram results. Thirty-five families/patients completed the clinical survey, and 45.5% of the families reported a noticeable improvement of hearing over time. CONCLUSIONS: Conductive hearing loss and SNHL are common in CdLS. More than 50% of the patients seen in an adult CdLS clinic reported improvement in hearing loss over time, and a subset of patients had an improvement in SNHL. In light of these findings, we recommend longitudinal evaluations of hearing loss in these patients with both auditory brainstem response and otoacoustic emissions testing if SNHL is identified. PMID- 27368473 TI - Helicobacter pylori seroprevalence in children with sleep-disordered breathing. AB - OBJECTIVE: Chronic Helicobacter pylori (HP) infection is considered to be a factor involved in obstructive sleep apnea syndrome (OSAS). This cross-sectional study examined the seroprevalence of HP in children with sleep-disordered breathing (SDB) in respect to OSAS severity and in reference to other common pediatric medical conditions. METHODS: Overnight polysomnography with pH-metry (PSG) was performed at a Sleep Laboratory (in the years 2008-2011). OSAS severity was determined based on Obstructive Apnea Index (OAI). Subjects were classified into primary snoring group (OAI < 1/hours), mild - moderate OSAS (OAI: 1-5/hour), and severe OSAS (OAI: >=5/hour). HP IgG was tested by an enzyme-linked immunosorbent assay in the SDB (n = 115) and reference (n = 387) groups [reference group consisted of 4 subgroups based on ICD-10 diagnoses encompassing conditions affecting the skin, respiratory system, food hypersensitivity, and gastrointestinal tract]. Analyses were performed by nonparametric statistical tests. RESULTS: HP seropositivity was 10.4% (12/115) in the SDB group and 11.6% (45/387) in the reference group. HP positive and negative subjects did not differ in PSG, acid gastro-esophageal reflux index nor in age, sex, nutritional status (BMI-z score), and hematological indices in the SDB group. Seropositivity was found in 16.7% of the primary snoring group, 10.2% of mild-moderate OSAS, and in 11.1% of severe OSAS (chi(2) p = 0.832). CONCLUSIONS: Children with SDB are not more predisposed to a chronic HP infection than children with other common chronic pediatric conditions. HP seropositivity does not influence OSAS severity but possible infection should none-the-less be considered on a case-by-case basis. PMID- 27368474 TI - Coblation-assisted management of pediatric airway stenosis. AB - OBJECTIVES: The treatment of pediatric airway stenosis represents a major challenge for the otolaryngologist. The aim of this study is to evaluate the use of bipolar radiofrequency plasma ablation (Coblation) in the treatment of pediatric airway stenosis. STUDY DESIGN: Retrospective case series. Tertiary care pediatric academic medical center. METHODS: The medical records of 6 pediatric patients at Cohen Children's Medical Center from July 2009 to December 2015 were reviewed. All cases involved the use of radiofrequency plasma ablation to address airway stenosis. Patient presentation, surgical intervention(s), post-operative course and complications were analyzed. RESULTS: All 6 cases involved pediatric airway stenosis, including glottic stenosis (2), bilateral vocal fold immobility (2), and intratracheal lesions (2). Coblation was used to perform a range of different procedures, including removal of scar/granulation tissue, partial arytenoidectomy, and posterior cordectomy. All patients experienced good results without major complications, perioperative, or post-operative sequellae. CONCLUSION: The results of this study suggest that radiofrequency plasma ablation may be an effective endoscopic tool for the treatment of pediatric airway stenosis. Further study and more patients are required as this technique becomes increasingly applied. PMID- 27368475 TI - Level of emotion comprehension in children with mid to long term cochlear implant use: How basic and more complex emotion recognition relates to language and age at implantation. AB - OBJECTIVES: The current study was designed with three main aims: To document the level of emotional comprehension skills, from basic to more complex ones, reached by a wide sample of cochlear implant (CI) deaf children with at least 36 months of device use; To investigate subjective and audiological factors that can affect their emotional development; To identify, if present, a "critical age", in which early intervention might positively affect adequate emotional competence development. DESIGN: This is an observational cohort study. Children with congenital severe/profound deafness were selected based on: aged by 4-11 years, minimum of 36 months of CI use, Italian as the primary language in the family; normal cognitive level and absence of associated disorders or socio-economic difficulties. Audiological characteristics and language development were assessed throughout standardized tests, to measure speech perception in quiet, lexical comprehension and production. The development of emotions' understanding was assessed using the Test of Emotion Comprehension (TEC) of Pons and Harris, a hierarchical developmental model, where emotion comprehension is organized in 3 Stages (external, mental and reflective). Statistical analysis was accomplished via the Spearman Rank Correlation Coefficient, to study the relationship between the personal and audiological characteristics; a multivariate linear regression analysis was carried out to find which variables were better associated with the standardized TEC values; a chi-squared test with Yate's continuity correction and Mann-Whitney U test were used to account for differences between continuous variables and proportions. RESULTS: 72 children (40 females, 32 males) with a mean age of 8.1 years were included. At TEC score, 57 children showed normal range performances (79.17% of recipients) and 15 fell below average (20.83% of recipients). The 16.63% of older subjects (range of age 8-12 years) didn't master the Stage 3 (reflective), which is normally acquired by 8 years of age and failed 2 or all the 3 items of this component. Subjects implanted within 18 months of age had better emotion comprehension skills. TEC results were also positively correlated with an early diagnosis, a longer implant use, better auditory skills and higher scores on lexical and morphosintactic tests. On the contrary, it was negatively correlated with the presence of siblings and the order of birth. The gender, the side and the severity of deafness, type of implant and strategy were not correlated. CONCLUSIONS: Early implanted children have more chance to develop adequate emotion comprehension, especially when the complex aspects are included, due to the very strong link between listening and language skills and emotional development. Furthermore, longer CI auditory experience along with early intervention allows an adequate communication development which positively influences the acquisition of such competencies. PMID- 27368477 TI - Biophysics in cancer: The relevance of drug-membrane interaction studies. AB - Lipidomics has been proving that membrane lipids play a crucial role in several cell functions and are involved in several pathologies, including cancer. In fact, beyond a scaffold where proteins and other components are embedded, the cell membrane can also act as a barrier or a target for anticancer drugs. From this point of view, the development of new chemotherapeutic agents should also take into account the role of the membrane in their activity. This Review aims to highlight the importance of anticancer drug-membrane interactions as a powerful strategy to improve cancer therapy. Biophysical techniques emerge, therefore, as essential tools to unveil such interactions. PMID- 27368479 TI - [Not Available]. PMID- 27368476 TI - Differences in expression of the cancer stem cell marker aldehyde dehydrogenase 1 among estrogen receptor-positive/human epidermal growth factor receptor type 2 negative breast cancer cases with early, late, and no recurrence. AB - BACKGROUND: The significance of the expression of aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, for predicting the recurrence of estrogen receptor (ER)-positive/human epidermal growth factor receptor type 2 (HER2) negative breast cancer is still poorly understood. The value of ALDH1 in predicting the time of recurrence remains unknown. METHODS: In total, 184 patients with early distant recurrence, 134 patients with late distant recurrence, and 321 control patients without recurrence for more than 10 years after starting initial treatment for ER-positive/HER2-negative breast cancer, registered in 9 institutions, were analyzed. We assessed relationships between ALDH1 and other clinicopathological features, and ALDH1 expression was compared among the three groups. The relationship between ALDH1 expression and overall survival after recurrence was also evaluated in each group. RESULTS: The rates of ALDH1 expression positivity (more than 1 %) in the early, late, and no recurrence groups were 18.4 %, 13.4 %, and 8.4 %, respectively. ALDH1 expression correlated significantly with lymph node metastases (p = 0.048) and the Ki-67 labeling index (p < 0.001) in the early recurrence group. Multivariate analysis revealed ALDH1 expression to be significantly higher in the early recurrence group than in the no recurrence group (adjusted OR 2.140, 95 % CI 1.144-4.003, p = 0.016). Moreover, there was a significant difference in ALDH1 expression between the early and no recurrence groups receiving adjuvant endocrine therapy and chemotherapy (adjusted OR 4.625, 95 % CI 1.881-12.474, p < 0.001). However, there was no difference in ALDH1 expression between the late and no recurrence groups in univariate analysis (OR 1.507, 95 % CI 0.738-2.998, p = 0.253). In multivariate analysis, ALDH1 was not a factor independently predicting overall survival after the detection of recurrence (adjusted OR 1.451, 95 % CI 0.985 2.085, p = 0.059). CONCLUSIONS: Among patients with ER-positive/HER2-negative breast cancer, ALDH1 expression was more common in those with early recurrence, and this expression was found to be associated with a more aggressive breast cancer phenotype than that in the patients without recurrence. Further study is needed to clarify the prognostic significance of the heterogeneity of cancer stem cells and to confirm their role in resistance to chemotherapy. PMID- 27368478 TI - [Not Available]. PMID- 27368480 TI - [Not Available]. PMID- 27368482 TI - [Not Available]. PMID- 27368481 TI - [Not Available]. PMID- 27368483 TI - [Not Available]. PMID- 27368484 TI - [Not Available]. PMID- 27368485 TI - [Not Available]. PMID- 27368486 TI - [Not Available]. PMID- 27368487 TI - [Not Available]. PMID- 27368488 TI - [Not Available]. PMID- 27368489 TI - [Not Available]. PMID- 27368490 TI - [Not Available]. PMID- 27368492 TI - [Not Available]. PMID- 27368491 TI - [Not Available]. PMID- 27368493 TI - [Not Available]. PMID- 27368495 TI - [Not Available]. PMID- 27368494 TI - [Not Available]. PMID- 27368496 TI - [Not Available]. PMID- 27368497 TI - [Not Available]. PMID- 27368499 TI - [Not Available]. PMID- 27368498 TI - [Not Available]. PMID- 27368500 TI - [Not Available]. PMID- 27368501 TI - Prognostic factors after hospitalization for COPD exacerbation. AB - INTRODUCTION: Hospitalizations for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are increasing in France. AECOPD are associated with impaired health status and increased health care costs. METHODS: Using data from the French national health insurance information system, we studied mortality, readmissions and lung function testing after discharge among adults hospitalized for AECOPD in 2013. RESULTS: The cumulative probabilities of death and readmission for EACOPD were 21% and 31% respectively. The survival was better among women, even after taking into account the other risk factors (age, previous hospitalization for AECOPD, comorbidities, exacerbation severity). In multivariate analysis, the risk of readmission was increased among men and people living in socially disadvantaged areas. A lung function testing was performed in 34% within 3 months after discharge. Female gender, advanced age, comorbidities and living in a disadvantaged area were associated with a lower frequency of lung function testing. CONCLUSIONS: Women had a better prognosis than men after AECOPD hospitalization. The frequency of lung function testing after discharge remained low, particularly among women and people living in disadvantaged areas. PMID- 27368502 TI - Coil Embolization for Ruptured Basilar Tip Aneurysm After Mechanical Thrombectomy for Acute Basilar Artery Occlusion. AB - BACKGROUND: There is no published report of ruptured cerebral aneurysm accompanied by target vessel occlusion. We present a case of ruptured basilar tip aneurysm with concomitant basilar artery (BA) occlusion. CASE DESCRIPTION: A 53 year-old man presented to our emergency room with the acute onset of disturbance. Plain head computed tomography showed diffuse subarachnoid hemorrhage. Computed tomography angiography and digital subtraction angiography showed a BA tip aneurysm with BA trunk occlusion. Endovascular treatment with mechanical thrombectomy using a stent retriever and coil embolization was performed. Clinical and radiologic results were good. The patient was discharged 30 days after onset (modified Rankin Scale score = 1). CONCLUSIONS: We were able to recanalize the BA trunk and perform coil embolization of the ruptured BA tip aneurysm. Our case is the first published report of a ruptured aneurysm with target large-vessel occlusion. Awareness of the issues raised in this case is required to determine the best treatment strategy, and preoperative consideration allows neurointerventionalists to avoid unpleasant surprises in the angiography suite. PMID- 27368503 TI - Predictors for Surgical Outcome of Laminoplasty for Cervical Spondylotic Myelopathy. AB - BACKGROUND: There were no precise researches showing which parameters with regard to degree of cervical stenosis and sagittal cervical alignment are the most crucial for surgical outcomes after laminoplasty for cervical spondylotic myelopathy (CSM). The objectives of this study were to investigate to what extent the preoperative parameters may have a direct influence on postoperative neurologic recovery, and to determine the crucial determinants of prognosis. METHODS: A retrospective review of 83 patients with CSM after laminoplasty was conducted. Magnetic resonance imaging parameters evaluation included presence/absence of signal change on T1 and T2 and anatomic measurements, including cervical canal compromise and cervical alignment. Data analysis involved logistic regressions and Spearman rank correlation coefficients. Receiver operator characteristic (ROC) curves were computed to evaluate the contribution of the original model. RESULTS: Univariate logistic regression showed that age (odds ratio = 0.822; 95% confidence interval, 0.729-0.927; P = 0.001), baseline Japanese Orthopedic Association (JOA) score (odds ratio = 1.700; 95% confidence interval, 1.158-2.496; P = 0.007), cervical curvature index (Ishihara) score (CCI) (odds ratio = 1.123; 95% confidence interval, 1.030-1.225; P = 0.008), maximum canal compromise (MCC) (odds ratio = 0.940; 95% confidence interval, 0.885-0.998; P = 0.041), and signal intensity (odds ratio = 0.139; 95% confidence interval, 0.033-0.580; P = 0.007) were independent prognostic indicators after laminoplasty. A ROC curve was computed based on the probability of the five predictors, with an area under the curve of 0.929 +/- 0.028. CONCLUSIONS: Age and baseline JOA scores were crucial clinical predictors of outcome after laminoplasty for patients with CSM. Regarding the predictive value, CCI, MCC, and patterns of signal intensity changes on T1-/T2-weighted images were crucial determinants of prognosis of neurologic outcome. PMID- 27368504 TI - A Subgaleal Hematoma That Turned Out to Be a B-Cell Lymphoma. AB - BACKGROUND: Subgaleal masses are relatively common in the clinical praxis, and after a trauma to the head, a subgaleal hematoma is usually suspected. However, other differential diagnoses, such as malignant tumors, should be kept in mind despite a history of a previous trauma. CASE DESCRIPTION AND CONCLUSIONS: We report a case of a subgaleal mass that was clinically and radiologically diagnosed as a subgaleal hematoma in a patient on antiplatelet therapy. The patient had a history of trauma to her head, but pathologic examination after surgery unexpectedly showed a malignant B-cell lymphoma. A review of the literature is also presented. PMID- 27368505 TI - Surgical Accuracy of 3-Tesla Versus 7-Tesla Magnetic Resonance Imaging in Deep Brain Stimulation for Parkinson Disease. AB - BACKGROUND: In deep brain stimulation (DBS), accurate placement of the lead is critical. Target definition is highly dependent on visual recognition on magnetic resonance imaging (MRI). We prospectively investigated whether the 7-T MRI enabled better visualization of targets and led to better placement of leads compared with the 1.5-T and the 3-T MRI. METHODS: Three patients with PD (mean, 55 years) were scanned on 1.5-, 3-, and 7-T MRI before surgery. Tissue contrast and signal-to-noise ratio were measured. Target coordinates were noted on MRI and during surgery. Differences were analyzed with post-hoc analysis of variance. RESULTS: The 7-T MRI demonstrated a significant improvement in tissue visualization (P < 0.005) and signal-to-noise ratio (P < 0.005). However, no difference in the target coordinates was found between the 7-T and the 3-T MRI. CONCLUSIONS: Although the 7-T MRI enables a significant better visualization of the DBS target in patients with PD, we found no clinical benefit for the placement of the DBS leads. PMID- 27368506 TI - Post-Traumatic Bifrontoparietal Extradural Hematoma with Superior Sagittal Sinus Detachment: A Case Report and Review of the Literature. AB - OBJECTIVE: To present, to our knowledge, the first case of a single bilateral extradural hematoma due to superior sagittal sinus detachment that was treated conservatively with an excellent outcome. METHODS: Bilateral extradural hematomas are a rare condition, accounting for only 2%-5% of all extradural hematomas. They can be either 2 distinct hematomas on either side or 1 single bilateral hematoma mostly due to sagittal sinus injury, with the latter being the most rare owing to the firm attachment of the sinus to its subperiosteal loggia. These hematomas usually require immediate surgical evacuation, as patients present with decreased level of consciousness, and have good postoperative outcomes. We present a bilateral extradural hematoma due to superior sagittal sinus injury, which was treated conservatively. RESULTS: The patient had an excellent recovery, with no residual neurological deficits and a Glasgow outcome scale of 5 on discharge. CONCLUSION: Bilateral extradural hematomas due to superior sagittal sinus injury almost always require surgical intervention. We present a patient who was treated conservatively with an excellent outcome and we also perform a review of the current literature. PMID- 27368507 TI - Epidural Venous Angioma Presenting with Spinal Cord Compression in a 42-Year-Old Woman with Previous History of Ovarian Malignancy. AB - BACKGROUND: Venous angioma is an extremely rare vascular malformation of the epidural space. To the best of our knowledge, only 5 cases have been documented to date and none has been reported in the setting of a previous malignancy. CASE DESCRIPTION: We report the case of a 42-year-old woman with a previous history of ovarian cancer, treated by surgery plus chemotherapy; who presented with signs of spinal cord compression for 3 weeks. Magnetic resonance imaging showed an intensely enhancing epidural mass at the T2-T6 level causing major spinal cord compression, for which urgent surgery was indicated. During surgery, the tumor was extremely hemorrhagic and the hemostasis was hazardous. Blood loss was estimated at 1.5 L, causing hemodynamic instability and requiring intensive resuscitation with fluids and blood transfusions. Gross total resection was achieved and the pathologic examination confirmed the diagnosis of venous angioma. The patient recovered quickly postoperatively and was able to walk independently within 2 weeks of starting intensive rehabilitation. She was symptom free with no clinical or radiologic evidence of recurrence at 1 year follow-up. CONCLUSIONS: Venous angioma should be included in the differential diagnosis of spinal epidural masses even in case of previous malignancy. Subtle imaging features should alert clinicians to this rare yet potentially life threatening condition. Surgery remains the cornerstone of the treatment and can result in remarkable recovery. PMID- 27368508 TI - The Outcome of Hypofractionated Stereotactic Radiosurgery for Large Vestibular Schwannomas. AB - OBJECTIVES: Stereotactic radiosurgery (SRS) for large vestibular schwannomas (VS) remains controversial. We studied the tumor local control and toxicity rates after hypofractionated SRS for VS > 3 cm. METHODS: A total of 587 patients with VS treated with SRS between 1998 and 2014 were reviewed retrospectively, and 30 Koos grade IV VSs were identified. There were 6 patients with neurofibromatosis 2 (NF2), 8 with cystic tumors, 22 with solid tumors, 19 who underwent primary CyberKnife (CK), and 11 with >3 cm after previous resection. Patients were treated by a median of 3 fractions at 18 Gy. RESULTS: After a median 97 months, the 3- and 10-year Kaplan-Meier estimates of local control were 85% and 80%, respectively, with 20% requiring salvage treatment. For patients who had previous tumor resection rather than primary CK, the estimates were 46% and 5%, respectively, with progression, and 3-year control rates of 71% and 94% (P = 0.008). Tumor control was also lower among NF2 versus non-NF2 patients (40% vs. 95%; P = 0.0014). Among patients with good clinical baselines before CK, 88% were functionally independent (modified Rankin Scale score, 0-2), 88% had good facial function (House-Brackmann grade I-II), and 38% had serviceable hearing (Gardner Robertson grade I-II) at last follow-up. Hearing worsening was more likely among patients treated with primary CK (33% vs. 90%; P = 0.04). CONCLUSIONS: Overall, 80% of large VSs were adequately controlled by CK with 97 months of median follow up. Patients with previous surgery and NF2 also appeared to have higher rates of tumor progression, and less favorable functional outcomes. PMID- 27368509 TI - Management Outcome of Brainstem Arteriovenous Malformations: The Role of Radiosurgery. AB - INTRODUCTION: Management decisions for brainstem arteriovenous malformations (AVMs) are complicated by balancing the risks of treatment and natural progression to hemorrhage. The present study seeks to compare radiosurgery and conservative management outcomes in brainstem AVMs. METHODS: We performed a retrospective review of patients with brainstem AVM seen at our institution from 1990 to 2013. Patients missing baseline information or those lost to follow-up were excluded. Clinical and angiographic characteristics and subsequent hemorrhagic risk were evaluated according to brainstem AVM location and treatment modality. RESULTS: We identified 30 patients with brainstem AVM with complete data. Mean age was 41.6 +/- 20.3 years, and 53.3% (n = 16) were male. Sixteen (53.3%) presented with hemorrhage. Twelve patients (40.0%) were conservatively managed, and 18 were treated. Sixteen (88.9%) of the treated patients underwent radiosurgery, 1 (5.6%) underwent surgery, and 1 (5.6%) underwent embolization only. Average follow-up period was 4.7 +/- 5.7 years, and 5 patients (16.7%) experienced recurrent hemorrhage, 3 of whom were in the radiosurgery group and 2 in the conservative group, giving an annual recurrent hemorrhage risk of 3.7% and 4.8%, respectively. Lesion obliteration was achieved in 8 patients (26.7%). Baseline clinical and angiographic factors were similar between the radiosurgery and conservative group. Obliteration was achieved in 43.8% of those treated with radiosurgery (P = 0.008). Despite similar baseline modified Rankin Scale scores, more patients had improvement of modified Rankin Scale score at last follow-up in the radiosurgery group (P = 0.004). Recurrent hemorrhage during follow-up was similar between the 2 groups (P = 0.887). CONCLUSIONS: Our results suggest that when patients with brainstem AVM are selected cautiously, radiosurgery may achieve obliteration and symptom relief without increasing subsequent hemorrhage risk. PMID- 27368510 TI - An Upper and Middle Cervical Spine Posterior Arch Defect Leading to Myelopathy and a Thoracic Spine Posterior Arch Defect. AB - BACKGROUND: Abnormalities of the posterior arches of the upper and middle cervical spine that can cause myelopathy are rare, and no reports of such defects at the thoracic spinal level have been published. CASE DESCRIPTION: A 29-year-old male patient reported right arm weakness and pain for 1 year. Magnetic resonance imaging of the cervical spine showed spinal canal stenosis at the C3-4 and C4-5 levels, as well as a posterior arch defect at the C2, 3, and 4 levels that was compressing the spinal cord. Three-dimensional cervical computed tomography (CT) showed that the spinous process and a piece of lamina were fused at each of the posterior C2, 3, and 4 levels, producing a free-floating bony structure. Spina bifida occulta was observed at C1. Osseous formation had failed between the lateral mass and spinous process at the C2 and C3 levels bilaterally, and the C4 level unilaterally. Three-dimensional thoracolumbar CT showed blocked vertebrae and spinous process fusion at T11 and T12. Osseous formation had failed between the lamina and spinous process at the T11 level unilaterally, and the T12 level bilaterally. The free-floating bony structure was successfully removed surgically. CONCLUSIONS: A posterior arch defect of the upper and middle cervical spine leading to myelopathy combined with the same defect at the thoracic spine is a rare disease. If this congenital defect is detected at any spinal level, whole-spine CT can be helpful for accurately diagnosing the congenital anomaly. PMID- 27368512 TI - If It Ain't Broke, Don't Fix It. PMID- 27368513 TI - Evolution of Cervical Spine Deformity Surgery and Ongoing Challenges. PMID- 27368511 TI - Is There An Optimal Time for Performing Cranioplasties? Results from a Prospective Multinational Study. AB - BACKGROUND: The optimal timing of cranioplasty remains uncertain. OBJECTIVE: We hypothesized that the risk of infections after primary cranioplasty in adult patients who underwent craniectomies for non-infection-related indications are no different when performed early or delayed. We tested this hypothesis in a prospective, multicenter, cohort study. METHODS: Data were collected prospectively from 5 neurosurgical centers in the United Kingdom, Malaysia, Singapore, and Bangladesh. Only patients older than 16 years from the time of the non-infection-related craniectomy were included. The recruitment period was over 17 months, and postoperative follow-up was at least 6 months. Patient baseline characteristics, rate of infections, and incidence of hydrocephalus were collected. RESULTS: Seventy patients were included in this study. There were 25 patients in the early cranioplasty cohort (cranioplasty performed before 12 weeks) and 45 patients in the late cranioplasty cohort (cranioplasty performed after 12 weeks). The follow-up period ranged between 16 and 34 months (mean, 23 months). Baseline characteristics were largely similar but differed only in prophylactic antibiotics received (P = 0.28), and primary surgeon performing cranioplasty (P = 0.15). There were no infections in the early cranioplasty cohort, whereas 3 infections were recorded in the late cohort. This did not reach statistical significance (P = 0.55). CONCLUSIONS: Early cranioplasty in non infection-related craniectomy is relatively safe. There does not appear to be an added advantage to delaying cranioplasties more than 12 weeks after the initial craniectomy in terms of infection reduction. There was no significant difference in infection rates or risk of hydrocephalus between the early and late cohorts. PMID- 27368520 TI - Homelessness. AB - An online learning resource aimed at community health professionals who work with homeless people has been launched by the Queen's Nursing Institute. The learning package contains six modules on. PMID- 27368521 TI - Out for consultation. PMID- 27368523 TI - Early years. AB - Healthcare professionals in Scotland who are involved in early years work now have an additional resource in the shape of NHS Scotland's Maternal and Early Years website, aimed at practitioners at all levels. The site includes evidence updates, news and events, and can be accessed at www.maternal-and-early years.org.uk. PMID- 27368522 TI - Sickness absence. AB - Staff sickness levels in the NHS vary dramatically across the country, but the Audit Commission says that by understanding and tackling the factors causing some of this variation the NHS can increase staff productivity, improve morale and save L290 million. It has produced a briefing that examines the local variation and cost of sickness absence to primary care trusts, NHS trusts and foundation trusts, and outlines where organisations can find more help and advice in cutting sickness absence rates. PMID- 27368524 TI - Commissioning. AB - A portal for clinicians, managers and other professionals involved in commissioning is available on NHS Networks. The Commissioning Zone brings together news, blogs, policy and guidance, reports and analysis, data, tools and resources, to promote sharing of useful information. Go to. PMID- 27368525 TI - Hospital food. AB - First Aid for Hospital Food, a report from the Soil Association, suggests some hospitals are falling short of acceptable standards in terms of the food they serve to patients. The report provides examples where hospitals have shown it is possible to source fresh, local and organic food with no cost increase and suggests ways in which other hospitals can achieve this. Go to http://tiny.cc/ce377. PMID- 27368526 TI - Patient safety. AB - The National Patient Safety Agency has published online its 'How to' guide on venous thromboembolism risk assessment for all patients admitted to hospital. The guide builds on existing resources and can be used to support implementation of the National Institute for Health and Clinical Excellence (NICE) Quality Standards Programme, Commissioning for Quality and Innovation requirements and NICE Guideline 92. PMID- 27368527 TI - The fine structure of the rectal pads of Zorotypus caudelli Karny (Zoraptera, Insecta). AB - The rectal pads of a species of the controversial polyneopteran order Zoraptera were examined using histological sections and TEM micrographs. Six pads are present along the thin rectal epithelium. Each pad consists of a few large principal cells surrounded by flattened junctional cells, which extend also beneath the principal cells. The cells are lined by a thin apical cuticle. No basal cells and no cavity have been observed beneath the pad. Principal cells have a regular layer of apical microvilli and are joined by intercellular septate junctions, which are interrupted by short dilatations of the intercellular space. At these levels the two adjacent plasma membranes are joined by short zonulae adhaerentes. In the cytoplasm, a rich system of strict associations between lateral plasma membranes and mitochondria forms scalariform junctions. Rectal pads share ultrastructural features with similar excretory organs of several neopteran groups, in particular with Blattodea (roaches and termites) and Thysanoptera, and are involved in fluid reabsorption and ion regulation. PMID- 27368528 TI - Systemic and regional pulmonary function after segmentectomy. AB - OBJECTIVE: Segmentectomy includes numerous kinds of procedures that may result in decreased postoperative pulmonary function. This causes controversy regarding the functional advantage of segmentectomy over lobectomy. To clarify the difference between the procedures, systemic and regional pulmonary functions of the resected segments must be examined. METHODS: Pulmonary function tests and lung perfusion single-photon emission computed tomography (SPECT) were prospectively conducted before and after segmentectomy in 117 patients who were divided into groups based on resection of <2 segments (n = 83), >=2 segments (n = 20), and left upper division (LUD) (n = 14). Left upper lobectomy (n = 13) was used as a control for the LUD group. Forced expiratory volume in 1 second (FEV1) of segment and lobe were measured from a fusion image of SPECT and computed tomography. RESULTS: Percentage of postoperative/preoperative pulmonary function was the highest in the <2 segments group (97% +/- 10%), which was followed by the >=2 segments group (90% +/- 9%), LUD group (84% +/- 7%), and left upper lobectomy group (83% +/- 7%), and the differences between the segmentectomy groups were significant (P < .001-.03), although there was no difference between the LUD and lobectomy groups. Whereas actual FEV1 of preserved lobes were significantly lower than the predicted value in all segmentectomy groups (P < .001), the percentage of actual/predicted value in the LUD group (43% +/- 19%) was significantly lower than those in the <2 (72% +/- 23%) and >=2 segments (68% +/- 30%) groups (P < .001 and P = .02, respectively). CONCLUSIONS: Segmentectomy decreased the pulmonary function with increasing number of resected segments. LUD segmentectomy decreased both systemic and lobar function significantly due to not only large resection, but also marked depression of the preserved lobe, resulting in similar decrease as lobectomy. PMID- 27368529 TI - [Not Available]. PMID- 27368530 TI - [HIV infection : Test and treatment]. AB - In Europe depending on the country 15-80 % of all individuals infected with human immunodeficiency virus (HIV) are either not aware of the diagnosis or are diagnosed later. An early HIV diagnosis could, however, considerably improve the prognosis of individuals infected with HIV and decrease the risk of new infections; therefore, in the presence of indicator diseases, such as sexually transmitted diseases, oral thrush, herpes zoster and lymphoma, the performance of a HIV test is of utmost importance. A newly diagnosed HIV infection represents an indication for starting antiretroviral combination therapy independent of the clinical stage or CD4 cell count. A decline of the viral burden to below the limit of detection and subsequent continuous suppression of viral replication can prevent transition from HIV to acquired immune deficiency syndrome (AIDS) and if started early enough a normal life expectancy can be achieved. Challenges which remain in HIV therapy are the lifelong daily intake of medication and the complex long-term adverse effects. PMID- 27368531 TI - [Neurocognitive disorders in old age : Role of pharmacotherapy in prevention and treatment]. AB - Neurocognitive disorders (e.g. dementia, mild cognitive impairment and delirium) belong to the most frequently occurring problems in older patients. For most types of dementia as well as for mild cognitive impairment no causal pharmacotherapy is currently available. This also applies to delirium, which should be primarily treated through the identification and elimination of predisposing factors while cautiously using symptomatic therapy with psychotropic drugs. Despite intensive ongoing research efforts the search for disease modifying drugs for the treatment of Alzheimer's dementia has not been successful. In the prevention and treatment of neurocognitive disorders, rational and evidence-based pharmacological interventions can nonetheless play an important role. Besides the limited benefits of symptomatic treatment with currently available anti-dementia drugs, this includes the strict management of medical risk factors as well as the avoidance of drugs with delirogenic and dementing side effects. PMID- 27368532 TI - Effect of Choline on the Composition and Degradation Enzyme of Extracellular Matrix of Mice Chondrocytes Exposed to Fluoride. AB - Choline has been shown to mediate damage of the chondrocyte matrix and degradation enzymes of mice exposed to fluoride (F). To test the action of choline, pregnant mice were treated with differing amounts of F and choline. Newborn mice were weaned at 21 days after birth and treated with the same doses of F and choline as they mothers for 12 weeks. Using hematoxylin-eosin (HE) staining, real-time PCR (RT-PCR), and western blotting, changes in the structure of the cartilage, the expression of mRNA and protein related to proteoglycans (PG), and degradation enzymes were detected. The RT-PCR results show that the expression of the Aggrecan (Acan), transforming growth factor beta (TGF-beta1), and Aggrecanases-1 gene were abnormal in the high fluoride (HiF) group, and treatments with choline reversed this phenomenon. The western blotting results show that the protein expression of Aggrecanases-1 was significantly increased in the HiF group (p < 0.01). These findings suggest that F can change the morphology of cartilage tissue, the gene expression of the Acan, TGF-beta1, Aggrecanases-1, and the protein expression of the Acan, and that choline can attenuate the effect of F. This may provide the basis for the treatment and prevention of fluorosis. PMID- 27368533 TI - Genetic characterization and transcription analyses of the European sea bass (Dicentrarchus labrax) isg15 gene. AB - Fish interferons are cytokines involved in its resistance to viral infections by inducing the transcription of several interferon-induced genes, such as isg15. The aim of the present study was the genetic characterization of the European sea bass isg15 gene, describing the regulatory motifs found in its sequence. In addition, an in vivo analysis of transcription in response to betanodavirus (RGNNV genotype) and poly I:C has been performed. The analysis of the resulting sequences showed that sea bass isg15 gene is composed of two exons and a single 276-bp intron located at the 5'-UTR region. The full length cDNA is 1143-bp, including a 102-bp 5'-UTR region, a 474-bp ORF, and a 291-bp 3'-UTR region. Several mRNA-regulatory elements, including three unusual ATTTA instability motifs in the intron, and four ATTTA motifs along with a cytoplasmic polyadenylation element in the 3'-UTR region, have been found in this sequence. The in vivo analyses revealed a similar kinetics and level of transcription in fish brain and head kidney after poly I:C inoculation; however, the induction caused by RGNNV started earlier in brain, where the upregulation of isg15 gene transcription was high. The present study contributes to further characterize the European sea bass IFN I response against RGNNV infections. PMID- 27368534 TI - Prostaglandin E2 promotes M2 polarization of macrophages via a cAMP/CREB signaling pathway and deactivates granulocytes in teleost fish. AB - The profile of prostaglandin (PG) production is determined by the differential expression of the enzymes involved in their production and degradation. Although the production of PGE2 by fish leukocytes has been relatively well studied in several fish species, knowledge of how its production is regulated, its biological activities and the signaling pathways activated by this PG is scant or even contradictory. In this work we show that in the teleost fish gilthead seabream (Sparus aurata L.) macrophages regulate PGE2 release mainly by inducing the expression of the genes encoding the enzymes responsible for its synthesis, while acidophilic granulocytes (AGs) not only induce these genes quickly after activation but also inhibit the expression of the genes encoding the enzymes responsible for PGE2 degradation at later time points. In addition, treatment of macrophages with PGE2 promoted their M2 polarization, which is characterized by high expression levels of interleukin-10, mannose-receptor c-type 1 and arginase 2 genes. In sharp contrast, PGE2 promoted the deactivation of AGs, since it decreased the production of reactive oxygen species and the expression of genes encoding pro-inflammatory cytokines. These differences are the result of the alternative signaling pathways used by PGE2 in macrophages and AGs, a cAMP/CREB signaling pathway operating in macrophages, but not in AGs, downstream of PGE2. Our data identify for the first time a role for professional phagocyte-derived PGE2 in the resolution of inflammation in fish and highlight key differences in the PGE2 signaling pathway in macrophages and granulocytes. PMID- 27368535 TI - Molecular and functional characterization of Toll-like receptor (Tlr)1 and Tlr2 in common carp (Cyprinus carpio). AB - Toll-like receptors (TLRs) are fundamental components of innate immunity that play significant roles in the defence against pathogen invasion. In this study, we present the molecular characterization of the full-length coding sequence of tlr1, tlr2a and tlr2b from common carp (Cyprinus carpio). Each is encoded within a single exon and contains a conserved number of leucine-rich repeats, a transmembrane region and an intracellular TIR domain for signalling. Indeed, sequence, phylogenetic and synteny analysis of carp tlr1, tlr2a and tlr2b support that these genes are orthologues of mammalian TLR1 and TLR2. The tlr genes are expressed in various immune organs and cell types. Furthermore, the carp sequences exhibited a good three-dimensional fit with the heterodimer structure of human TLR1-TLR2, including the potential to bind to the ligand Pam3CSK4. This supports the possible formation of carp Tlr1-Tlr2 heterodimers. However, we were unable to demonstrate Tlr1/Tlr2-mediated ligand binding in transfected cell lines through NF-kappaB activation, despite showing the expression and co-localization of Tlr1 and Tlr2. We discuss possible limitations when studying ligand-specific activation of NF-kappaB after expression of Tlr1 and/or Tlr2 in human but also fish cell lines and we propose alternative future strategies for studying ligand binding properties of fish Tlrs. PMID- 27368536 TI - Molecular and immune response characterizations of a novel AIF and cytochrome c in Litopenaeus vannamei defending against WSSV infection. AB - Apoptosis inducing factor (AIF) and cytochrome c (CYC) are two mitochondrial apoptogenic factors. In the present study, the cDNA sequences of AIF (LvAIF) and CYC (LvCYC) were cloned from Pacific white shrimp, Litopenaeus vannamei. The LvAIF was 1664 bp, including a 5'-terminal untranslated region (UTR) of 154 bp, an open reading frame (ORF) of 1323 bp encoding a polypeptide of 440 amino acids (aa) and a 3' UTR of 187 bp. The LvCYC was 582 bp, including a 50 bp 5' UTR, a 315 bp ORF encoding for 104 aa, and a 217 bp 3' UTR. The deduced protein of LvAIF contained a conserved Pyr_redox and AIF_C domain at the N-terminal and the predicted LvCYC included a conservative cytochrome_C domain, respectively. Phylogenetic analysis revealed that LvAIF belonged to AIF1 subfamily and showed a close relationship with AIF1 from vertebrates and LvCYC showed the closest relationship with its counterparts from shrimp Marsupenaeus japonicus. Tissue expression profiles showed that both LvAIF and LvCYC existed in most tissues, with the most predominant expression of LvAIF in intestine, then followed muscle and the weakest expression in gill. The highest expression of LvCYC was detected in muscle, and the weakest expression was in hemocytes. Additionally, after white spot syndrome virus (WSSV) infection, the significant up-regulation of LvAIF, LvCYC and caspase 3 transcripts and the increase of pro-caspase 3 and active caspase 3 protein were detected at most time points (P < 0.05). However, all of the three genes down-regulated in hemocytes in the early stage after WSSV infection. WSSV proliferation and shrimp mortality showed a time-dependent manner and the production of ROS in hemocytes were significantly increased at 6 and 24 h after infection. Our results showed that the apoptotic genes AIF, CYC and caspase 3 might play crucial roles in hepatopancreas, however, the production of ROS in hemocytes might be important in shrimp defense against WSSV infection. PMID- 27368537 TI - De novo annotation of the immune-enriched transcriptome provides insights into immune system genes of Chinese sturgeon (Acipenser sinensis). AB - Chinese sturgeon (Acipenser sinensis), one of the oldest extant actinopterygian fishes with very high evolutionary, economical and conservation interest, is considered to be one of the critically endangered aquatic animals in China. Up to date, the immune system of this species remains largely undetermined with little sequence information publicly available. Herein, the first comprehensive transcriptome of immune tissues for Chinese sturgeon was characterized using Illumina deep sequencing. Over 67 million high-quality reads were generated and de novo assembled into the final set of 91,739 unique sequences. The annotation pipeline revealed that 25,871 unigenes were successfully annotated in the public databases, of which only 2002 had significant match to the existing sequences for the genus Acipenser. Overall 22,827 unigenes were categorized into 52 GO terms, 12,742 were classified into 26 KOG categories, and 4968 were assigned to 339 KEGG pathways. A more detailed annotation search showed the presence of a notable representation of immune-related genes, which suggests that this non-teleost actinopterygian fish harbors the same intermediates as in the well known immune pathways from mammals and teleosts, such as pattern recognition receptor (PRR) signaling pathway, JAK-STAT signaling pathway, complement and coagulation pathway, T-cell receptor (TCR) and B-cell receptor (BCR) signaling pathways. Additional genetic marker discovery led to the retrieval of 20,056 simple sequence repeats (SSRs) and 327,140 single nucleotide polymorphisms (SNPs). This immune-enriched transcriptome of Chinese sturgeon represents a rich resource that adds to the currently nascent field of chondrostean fish immunogenetics and furthers the conservation and management of this valuable fish. PMID- 27368538 TI - Synthetic hepcidin from fish: Uptake and protection against Vibrio anguillarum in sea bass (Dicentrarchus labrax). AB - The generation of a variety of new therapeutic agents to control and reduce the effects of pathogen in aquaculture is urgently needed. The antimicrobial peptides (AMPs) are one of the major components of the innate defenses and typically have broad-spectrum antimicrobial activity. However, absorption and distributions of exogenous AMPs for therapeutics application on farmed fish species need to be studied. Previous studies in our laboratory have shown the properties of hepcidin as an effective antimicrobial peptide produced in fish in response to LPS and iron. Therefore, we decided to investigate the antimicrobial activity of four synthetic variants of hepcidin against Vibrio anguillarum in vitro, and using the more effective peptide we demonstrated the pathogen's ability to protect against the infection in European Sea bass. Additionally the uptake of this peptide after ip injection was demonstrated, reaching its distribution organs such as intestine, head kidney, spleen and liver. The synthetic peptide did not show cytotoxic effects and significantly reduced the accumulated mortalities percentage (23.5%) compared to the European Sea bass control (72.5%) at day 21. In conclusion, synthetic hepcidin shows antimicrobial activity against V. anguillarum and the in vivo experiments suggest that synthetic hepcidin was distributed trough the different organs in the fish. Thus, synthetic hepcidin antimicrobial peptide could have high potential for therapeutic application in farmed fish species. PMID- 27368539 TI - Identification and expression analysis of TLR2 in mucosal tissues of turbot (Scophthalmus maximus L.) following bacterial challenge. AB - The pathogen recognition receptors (PRRs), which can recognize the conserved pathogen-associated molecular patterns (PAMPs) of the bacteria, play key roles in the mucosal surfaces for pathogen recognition and activation of immune signaling pathways. However, our understanding of the PRRs and their activities in mucosal surfaces in the critical early time points during pathogen infection is still limited. Towards to this end, here, we sought to identify the Toll-like receptor 2 (TLR2) in turbot as well as its expression profiles in mucosal barriers following bacterial infection in the early time points. The full-length TLR2 transcript consists of open reading frame (ORF) of 2451 bp encoding the putative peptide of 816 amino acids. The phylogenetic analysis revealed the turbot TLR2 showed the closest relationship to Paralichthys olivaceus. The TLR2 mRNA expression could be detected in all examined tissues, with the most abundant expression level in liver, and the lowest expression level in skin. In addition, TLR2 showed different expression patterns following Vibrio anguillarum and Streptococcus iniae infection, but was up-regulated following both challenge, especially post S. iniae challenge. Characterization of TLR2 will probably contribute to understanding of a number of infectious diseases and broaden the knowledge of interactions between host and pathogen, which will eventually help in the development of novel intervention strategies for farming turbot. PMID- 27368541 TI - Spirulina elicits the activation of innate immunity and increases resistance against Vibrio alginolyticus in shrimp. AB - The effect of Spirulina dried powder (SDP) on the immune response of white shrimp Litopenaeus vannamei was studied in vitro and in vivo. Incubating shrimp haemocytes in 0.5 mg ml(-1) SDP caused the degranulation of haemocytes and a reduction in the percentage of large cells within 30 min. Shrimp haemocytes incubated in 1 mg ml(-1) SDP significantly increased their phenoloxidase (PO) activity, serine proteinase activity, and respiratory burst activity (RB, release of superoxide anion). A recombinant protein of lipopolysaccharide and beta-1,3 glucan binding protein (LGBP) of the white shrimp was produced, named rLvLGBP, and examined for its binding with SDP. An ELISA binding assay showed that rLvLGBP binds to SDP with a dissociation constant of 0.0507 MUM. In another experiment, shrimp fed diets containing SDP at 0 (control), 30, and 60 g kg(-1) after four weeks were examined for LGBP transcript level and lysozyme activity, as well as phagocytic activity, clearance efficiency, and resistance to Vibrio alginolyticus. These parameters were significantly higher in shrimp receiving diets containing SDP at 60 g kg(-1) or 30 g kg(-1) than in controls. In conclusion, shrimp haemocytes receiving SDP provoked the activation of innate immunity as evidenced by the recognition and binding of LGBP, degranulation of haemocytes, reduction in the percentage of large cells, increases in PO activity, serine proteinase activity, superoxide anion levels, and up-regulated LGBP transcript levels. Shrimp receiving diets containing SDP had increased lysozyme activity and resistance against V. alginolyticus infection. This study showed the mechanism underlying the immunostimulatory action of Spirulina and its immune response in shrimp. PMID- 27368540 TI - Hematological and Immunological plasma assays for grass carp (Ctenopharyngodon idella) infected with Aeromonas hydrophila as an immune model in carp aquaculture. AB - Aeromonas hydrophila is the causative agent of bacterial septicemia, a common disease observed in grass carp, Ctenopharyngodon idella. In our study, C. idella specimens were infected with A. hydrophila, and parameters of Hematological and Immunological plasma parameters were monitored. At blood cell level, levels of red blood cells (RBCs), hematocrit (HCT), and mean corpuscular volume (MCV) showed no differences between the treatment and control groups, but levels of white blood cells (WBCs) increased. The monocyte and neutrophil varied significant according to stimulation by A. hydrophila at 1 DPI, the thrombocyte and lymphocyte at 14 and 21 DPI. At serum level, total protein, lysozyme, and IgM increased at the early infection phase and then decreased at other time points; however, peroxidase levels were significantly lower in the treatment group than that in the control group during the early infection phase. ACH50 was significantly higher in the treatment group than that in the control group during the late infection phase. On the basis of the results, we suggest that innate and adaptive immune mechanisms of C. idella are able to neutralize the virulence factors secreted by A. hydrophila. Our findings would help in understanding the mechanisms underlying resistance to infection by A. hydrophila. PMID- 27368542 TI - Apolipoprotein A-I in Labeo rohita: Cloning and functional characterisation reveal its broad spectrum antimicrobial property, and indicate significant role during ectoparasitic infection. AB - Apolipoprotein A-I (ApoA-I) is the most abundant and multifunctional high-density lipoprotein (HDL) having a major role in lipid transport and potent antimicrobial activity against a wide range of microbes. In this study, a complete CDS of 771 bp of Labeo rohita (rohu) ApoA-I (LrApoA-I) encoding a protein of 256 amino acids was amplified, cloned and sequenced. Tissue specific transcription analysis of LrApoA-I revealed its expression in a wide range of tissues, with a very high level of expression in liver and spleen. Ontogenic study of LrApoA-I expression showed presence of transcripts in milt and 3 h post-fertilization onwards in the larvae. The expression kinetics of LrApoA-I was studied upon infection with three different types of pathogens to elucidate its functional significance. Its expression was found to be up-regulated in the anterior kidney of L. rohita post infection with Aeromonas hydrophila. Similarly following poly I:C (poly inosinic:cytidylic) stimulation, the transcript levels increased in both the anterior kidney and liver tissues. Significant up-regulation of LrApoA-I expression was observed in skin, mucous, liver and anterior kidney of the fish challenged with the ectoparasite Argulus siamensis. Immunomodulatory effect of recombinant LrApoA-I (rApoA-I) produced in Escherichia coli was demonstrated against A. hydrophila challenge in vivo. L. rohita administered with rApoA-I at a dose of 100 MUg exhibited significantly higher protection (~55%) upon challenge with A. hydrophila 12 h post-administration of the protein, in comparison to that observed in control group, along with higher level of expression of immune related genes. The heightened expression of ApoA-I observed post-infection reflected its involvement in immune responses against a wide range of infections including bacterial, viral as well as parasitic pathogens. Our results also suggest the possibility of using rApoA-I as an immunostimulant, particularly rendering protection against A. hydrophila. PMID- 27368543 TI - Identification of differentially expressed genes in the spleens of polyriboinosinic polyribocytidylic acid (poly I:C)-stimulated yellow catfish Pelteobagrus fulvidraco. AB - The yellow catfish, Pelteobagrus fulvidraco (Siluriformes: Bagridae) is an economically important fish in China. However, genomic research and resources on this species are largely unavailable and still in infancy. In the present study, we constructed a cDNA library following poly I:C injection to screen for immune response genes in the spleens of P. fulvidraco using suppression subtractive hybridization (SSH). A total of 420 putative expressed sequence tag (EST) clones were identified at 24 h post-injection, which contain 103 genes consisting of 25 immune response genes, 12 cytoskeleton genes, 7 cell cycle and apoptosis genes, 7 respiration and energy metabolism genes, 7 transport genes, 26 metabolism genes, 10 stress response genes, 9 translational regulation genes, and 71 unknown genes. Real-time quantitative reverse transcription-PCR (qRT-PCR) results revealed that a set of randomly selected immune response genes were identified to be up regulated after 24 h of poly I:C stimulation compared to controls. Our study provides an annotation of immune genes in detail and insight into fish immunity. PMID- 27368546 TI - [Not Available]. PMID- 27368545 TI - [Not Available]. PMID- 27368547 TI - [Not Available]. PMID- 27368544 TI - Requirements and comparative analysis of reverse genetics for bluetongue virus (BTV) and African horse sickness virus (AHSV). AB - BACKGROUND: Bluetongue virus (BTV) and African horse sickness virus (AHSV) are distinct arthropod borne virus species in the genus Orbivirus (Reoviridae family), causing the notifiable diseases Bluetongue and African horse sickness of ruminants and equids, respectively. Reverse genetics systems for these orbiviruses with their ten-segmented genome of double stranded RNA have been developed. Initially, two subsequent transfections of in vitro synthesized capped run-off RNA transcripts resulted in the recovery of BTV. Reverse genetics has been improved by transfection of expression plasmids followed by transfection of ten RNA transcripts. Recovery of AHSV was further improved by use of expression plasmids containing optimized open reading frames. RESULTS: Plasmids containing full length cDNA of the 10 genome segments for T7 promoter-driven production of full length run-off RNA transcripts and expression plasmids with optimized open reading frames (ORFs) were used. BTV and AHSV were rescued using reverse genetics. The requirement of each expression plasmid and capping of RNA transcripts for reverse genetics were studied and compared for BTV and AHSV. BTV was recovered by transfection of VP1 and NS2 expression plasmids followed by transfection of a set of ten capped RNAs. VP3 expression plasmid was also required if uncapped RNAs were transfected. Recovery of AHSV required transfection of VP1, VP3 and NS2 expression plasmids followed by transfection of capped RNA transcripts. Plasmid-driven expression of VP4, 6 and 7 was also needed when uncapped RNA transcripts were used. Irrespective of capping of RNA transcripts, NS1 expression plasmid was not needed for recovery, although NS1 protein is essential for virus propagation. Improvement of reverse genetics for AHSV was clearly demonstrated by rescue of several mutants and reassortants that were not rescued with previous methods. CONCLUSIONS: A limited number of expression plasmids is required for rescue of BTV or AHSV using reverse genetics, making the system much more versatile and generally applicable. Optimization of reverse genetics enlarge the possibilities to rescue virus mutants and reassortants, and will greatly benefit the control of these important diseases of livestock and companion animals. PMID- 27368548 TI - [Not Available]. PMID- 27368549 TI - [Not Available]. PMID- 27368550 TI - [Not Available]. PMID- 27368551 TI - [Not Available]. PMID- 27368553 TI - [Not Available]. PMID- 27368552 TI - [Not Available]. PMID- 27368554 TI - [Not Available]. PMID- 27368556 TI - [Not Available]. PMID- 27368555 TI - [Not Available]. PMID- 27368557 TI - [Not Available]. PMID- 27368558 TI - [Not Available]. PMID- 27368559 TI - [Not Available]. PMID- 27368560 TI - [Not Available]. PMID- 27368562 TI - [Not Available]. PMID- 27368561 TI - [Not Available]. PMID- 27368563 TI - [Not Available]. PMID- 27368564 TI - [Not Available]. PMID- 27368565 TI - [Not Available]. PMID- 27368566 TI - [Not Available]. PMID- 27368568 TI - [Not Available]. PMID- 27368567 TI - [Not Available]. PMID- 27368569 TI - [Not Available]. PMID- 27368570 TI - [Not Available]. PMID- 27368571 TI - [Not Available]. PMID- 27368572 TI - [Not Available]. PMID- 27368573 TI - [Not Available]. PMID- 27368574 TI - [Not Available]. PMID- 27368575 TI - [Not Available]. PMID- 27368576 TI - [Not Available]. PMID- 27368577 TI - [Not Available]. PMID- 27368579 TI - [Not Available]. PMID- 27368578 TI - Current Topics in Canine and Feline Obesity. AB - The domestication and urbanization of dogs and cats has dramatically altered their environment and behavior. Human and pet obesity is a global concern, particularly in developed countries. An increased incidence of chronic disease is associated with obesity secondary to low-grade systemic inflammation. This article reviews current research into the genetic, dietary, and physiologic factors associated with obesity, along with use of "omics" technology to better understand and characterize this disease. PMID- 27368580 TI - [Not Available]. PMID- 27368581 TI - [Not Available]. PMID- 27368582 TI - [Not Available]. PMID- 27368583 TI - [Not Available]. PMID- 27368584 TI - [Not Available]. PMID- 27368585 TI - High affinity anti-BSEP antibodies after liver transplantation for PFIC-2 - Successful treatment with immunoadsorption and B-cell depletion. AB - PFIC due to BSEP mutations (PFIC type 2) often necessitates OLT. It has recently been recognized that some PFIC-2 patients develop phenotypic disease recurrence post-OLT due to the appearance of anti-BSEP antibodies. Here, we describe a boy who became cholestatic four yr after OLT during modification of immunosuppression. Canalicular antibody deposits were detected in biopsies of the transplant and antibodies specifically reacting with BSEP were identified at high titers in his serum. These antibodies bound extracellular epitopes of BSEP and inhibited BS transport and were assumed to cause disease recurrence. Consequently, anti-BSEP antibody depletion was pursued by IA and B-cell depletion by anti-CD20 antibodies (rituximab) along with a switch of immunosuppression. This treatment resulted in prolonged relief of symptoms. Depletion of pathogenic anti-BSEP antibodies causing AIBD after OLT in PFIC-2 patients should be considered as a central therapeutic goal. PMID- 27368586 TI - [Not Available]. PMID- 27368587 TI - [Not Available]. PMID- 27368588 TI - [Not Available]. PMID- 27368589 TI - [Not Available]. PMID- 27368590 TI - [Not Available]. PMID- 27368592 TI - [Not Available]. PMID- 27368591 TI - [Not Available]. PMID- 27368593 TI - [Not Available]. PMID- 27368594 TI - [Not Available]. PMID- 27368595 TI - [Not Available]. PMID- 27368596 TI - [Not Available]. PMID- 27368597 TI - [Not Available]. PMID- 27368598 TI - [Not Available]. PMID- 27368599 TI - [Not Available]. PMID- 27368600 TI - [Not Available]. PMID- 27368602 TI - [Not Available]. PMID- 27368601 TI - [Not Available]. PMID- 27368603 TI - [Not Available]. PMID- 27368604 TI - [Not Available]. PMID- 27368605 TI - [Not Available]. PMID- 27368606 TI - [Not Available]. PMID- 27368607 TI - [Not Available]. PMID- 27368610 TI - Host cell remodelling in malaria parasites: a new pool of potential drug targets. AB - When in their human hosts, malaria parasites spend most of their time housed within vacuoles inside erythrocytes and hepatocytes. The parasites extensively modify their host cells to obtain nutrients, prevent host cell breakdown and avoid the immune system. To perform these modifications, malaria parasites export hundreds of effector proteins into their host cells and this process is best understood in the most lethal species to infect humans, Plasmodium falciparum. The effector proteins are synthesized within the parasite and following a proteolytic cleavage event in the endoplasmic reticulum and sorting of mature proteins into the correct vesicular trafficking pathway, they are transported to the parasite surface and released into the vacuole. The effector proteins are then unfolded before extrusion across the vacuole membrane by a unique translocon complex called Plasmodium translocon of exported proteins. After gaining access to the erythrocyte cytoplasm many effector proteins continue their journey to the erythrocyte surface by utilising various membranous structures established by the parasite. This complex trafficking pathway and a large number of the effector proteins are unique to Plasmodium parasites. This pathway could, therefore, be developed as new drug targets given that protein export and the functional role of these proteins are essential for parasite survival. This review explores known and potential drug targetable steps in the protein export pathway and strategies for discovering novel drug targets. PMID- 27368609 TI - Follow your nose: leaf odour as an important foraging cue for mammalian herbivores. AB - Studies of odour-driven foraging by mammals focus on attractant cues emitted by flowers, fruits, and fungi. Yet, the leaves of many plant species worldwide produce odour, which could act as a cue for foraging mammalian herbivores. Leaf odour may thus improve foraging efficiency for such herbivores in many ecosystems by reducing search time, particularly but not only, for plants that are visually obscured. We tested the use of leaf odour by a free-ranging mammalian browser, the swamp wallaby (Wallabia bicolor) to find and browse palatable tree seedlings (Eucalyptus pilularis). Wallabies visited patches non-randomly with respect to the presence of seedlings. In the absence of visual plant cues, they used leaf odour (cut seedlings in vials) to find patches earlier, and visited and investigated them more often than control patches (empty vials), supporting the hypothesis that wallabies used seedling odour to enhance search efficiency. In contrast, the grey kangaroo (Macropus giganteus), a grazer, showed no response to seedling odour. When the availability of seedling visual and olfactory cues was manipulated, wallabies browsed seedlings equally quickly in all treatments: upright (normal cues), pinned to the ground (reduced visual cues), and upright plus pinned seedlings (double olfactory cues). Odour cues play a critical role in food-finding by swamp wallabies, and these animals are finely tuned to detecting these cues with their threshold for detection reached by odours from only a single plant. The global significance of leaf odour in foraging by mammalian herbivores consuming conifers, eucalypts, and other odour-rich species requires greater attention. PMID- 27368608 TI - Proteomic profiling of cellular steatosis with concomitant oxidative stress in vitro. AB - BACKGROUND: Nutrient excess underpins the development of nonalcoholic fatty liver disease (NAFLD). The ensuing metabolic derangement is characterised by increased cellular respiration, oxidative stress and mitochondrial impairment. We have previously recapitulated these events in an in vitro cellular steatosis model. Here, we examined the distinct patterns of protein expression involved using a proteomics approach. METHODS: Human hepatoblastoma C3A cells were treated with a combination of energy substrates; lactate (L), pyruvate (P), octanoate (O) and ammonia (N). Proteins extracts were trypsinized and analyzed on a capillary HPLC OrbitrapXL mass spectrometer. Proteins were quantified using a label-free intensity based approach. Functional enrichment analysis was performed using ToppCluster via Gene Ontology (GO) database. RESULTS: Of the 1327 proteins identified, 104 were differentially expressed between LPON and untreated cells (defined as: >=2 peptides; fold change >=1.5; p-value <0.05). Seventy of these were upregulated with LPON. Functional enrichment analysis revealed enhanced protein biosynthesis accompanied by downregulation of histones H2A type 1-A, H1.2, H1.5 and H1.0I in LPON cells. Lipid binding annotations were also enriched as well as proteins involved in cholesterol synthesis, uptake and efflux. Increased expression of aldo-keto reductase family 1, member C1 and C3 suggests enhanced sterol metabolism and increased ROS-mediated lipid peroxidation. CONCLUSIONS: The surge of energy substrates diverts free fatty acid metabolism towards pathways that can mitigate lipotoxicity. The histones depletion may represent an adaptation to increased protein synthesis. However, this can also expose DNA to oxidative stress thus should be explored further in the context of NAFLD progression. PMID- 27368612 TI - [Not Available]. PMID- 27368611 TI - Cryptic Eimeria genotypes are common across the southern but not northern hemisphere. AB - The phylum Apicomplexa includes parasites of medical, zoonotic and veterinary significance. Understanding the global distribution and genetic diversity of these protozoa is of fundamental importance for efficient, robust and long lasting methods of control. Eimeria spp. cause intestinal coccidiosis in all major livestock animals and are the most important parasites of domestic chickens in terms of both economic impact and animal welfare. Despite having significant negative impacts on the efficiency of food production, many fundamental questions relating to the global distribution and genetic variation of Eimeria spp. remain largely unanswered. Here, we provide the broadest map yet of Eimeria occurrence for domestic chickens, confirming that all the known species (Eimeria acervulina, Eimeria brunetti, Eimeria maxima, Eimeria mitis, Eimeria necatrix, Eimeria praecox, Eimeria tenella) are present in all six continents where chickens are found (including 21 countries). Analysis of 248 internal transcribed spacer sequences derived from 17 countries provided evidence of possible allopatric diversity for species such as E. tenella (FST values ?0.34) but not E. acervulina and E. mitis, and highlighted a trend towards widespread genetic variance. We found that three genetic variants described previously only in Australia and southern Africa (operational taxonomic units x, y and z) have a wide distribution across the southern, but not the northern hemisphere. While the drivers for such a polarised distribution of these operational taxonomic unit genotypes remains unclear, the occurrence of genetically variant Eimeria may pose a risk to food security and animal welfare in Europe and North America should these parasites spread to the northern hemisphere. PMID- 27368613 TI - [Not Available]. PMID- 27368614 TI - [Not Available]. PMID- 27368615 TI - [Not Available]. PMID- 27368616 TI - [Not Available]. PMID- 27368617 TI - Pragmatics and the aims of language evolution. AB - Pragmatics has historically played a relatively peripheral role in language evolution research. This is a profound mistake. Here I describe how a pragmatic perspective can inform language evolution in the most fundamental way: by making clear what the natural objects of study are, and hence what the aims of the field should be. PMID- 27368618 TI - Precursors to language: Social cognition and pragmatic inference in primates. AB - Despite their differences, human language and the vocal communication of nonhuman primates share many features. Both constitute forms of coordinated activity, rely on many shared neural mechanisms, and involve discrete, combinatorial cognition that includes rich pragmatic inference. These common features suggest that during evolution the ancestors of all modern primates faced similar social problems and responded with similar systems of communication and cognition. When language later evolved from this common foundation, many of its distinctive features were already present. PMID- 27368619 TI - Primate vocal production and the riddle of language evolution. AB - Trying to uncover the roots of human speech and language has been the premier motivation to study the signalling behaviour of nonhuman primates for several decades. Focussing on the question of whether we find evidence for linguistic reference in the production of nonhuman primate vocalizations, I will first discuss how the criteria used to diagnose referential signalling have changed over time, and will then turn to the paradigmatic case of semantic communication in animals, the alarm calls of vervet monkeys, Chlorocebus pygerythrus. A recent in-depth analysis of the original material revealed that, while the alarm calls could be well distinguished, calls of similar structure were also used in within- and between-group aggression. This finding is difficult to reconcile with the idea that calls denote objects in the environment. Furthermore, nonhuman primates show only minimal signs of vocal production learning, one key prerequisite for conventionalized and symbolic communication. In addition, the structure of calls in different populations or closely related species is highly conserved. In conclusion, any continuity between nonhuman primate and human communication appears to be found at the level of the processing of signals. Why and how the ancestors of our own species one day began to talk to each other continues to be an enigma. Future research should focus on changes in the neural structure supporting volitional control over vocalizations, the gene networks associated with vocal production, and the developmental processes involved in the integration of production and perception of vocalizations. PMID- 27368620 TI - How can we detect when language emerged? AB - Views differ radically as to how deep the roots of language lie in human phylogeny, largely because prior to the development of writing systems, this striking human attribute has to be inferred from indirect proxies preserved in the material record. Here I argue that the most appropriate such archaeological proxies encode the modern human symbolic cognitive system from which language emerges. Throughout the 2.5 million years or more for which an archaeological record has existed, change has been both sporadic and rare-until symbolic objects and behaviors begin to appear, well within the tenure of our highly apomorphic species Homo sapiens. I propose that the biology underwriting our unusual cognitive and linguistic systems was acquired in the major developmental reorganization that gave rise to our anatomically distinctive species around 200,000 years ago in Africa. However, the material record indicates that this new potential lay fallow for around 100,000 years, following which it was released by what was necessarily a behavioral stimulus. By far the best candidate for that stimulus is the spontaneous invention of language, which is plausibly underwritten by a relatively simple mental algorithm, and could readily have spurred symbolic cognitive processes in a feedback process. None of this means that earlier hominid vocal communication systems were not complex, or that extinct hominid species were not highly intelligent. But it does emphasize the qualitative distinctiveness of both modern symbolic cognition and language. PMID- 27368621 TI - Where have all the (ape) gestures gone? AB - Comparative analysis of the gestural communication of our nearest animal relatives, the great apes, implies that humans should have the biological potential to produce and understand 60-70 gestures, by virtue of shared common descent. These gestures are used intentionally in apes to convey separate requests, rather than as referential items in syntactically structured signals. At present, no such legacy of shared gesture has been described in humans. We suggest that the fate of "ape gestures" in modern human communication is relevant to the debate regarding the evolution of language through a possible intermediate stage of gestural protolanguage. PMID- 27368622 TI - Preface to the Special Issue on the Biology and Evolution of Language. PMID- 27368623 TI - What bats have to say about speech and language. AB - Understanding the biological foundations of language is vital to gaining insight into how the capacity for language may have evolved in humans. Animal models can be exploited to learn about the biological underpinnings of shared human traits, and although no other animals display speech or language, a range of behaviors found throughout the animal kingdom are relevant to speech and spoken language. To date, such investigations have been dominated by studies of our closest primate relatives searching for shared traits, or more distantly related species that are sophisticated vocal communicators, like songbirds. Herein I make the case for turning our attention to the Chiropterans, to shed new light on the biological encoding and evolution of human language-relevant traits. Bats employ complex vocalizations to facilitate navigation as well as social interactions, and are exquisitely tuned to acoustic information. Furthermore, bats display behaviors such as vocal learning and vocal turn-taking that are directly pertinent for human spoken language. Emerging technologies are now allowing the study of bat vocal communication, from the behavioral to the neurobiological and molecular level. Although it is clear that no single animal model can reflect the complexity of human language, by comparing such findings across diverse species we can identify the shared biological mechanisms likely to have influenced the evolution of human language. PMID- 27368624 TI - Marr's levels and the minimalist program. AB - A simple change to a cognitive system at Marr's computational level may entail complex changes at the other levels of description of the system. The implementational level complexity of a change, rather than its computational level complexity, may be more closely related to the plausibility of a discrete evolutionary event causing that change. Thus the formal complexity of a change at the computational level may not be a good guide to the plausibility of an evolutionary event introducing that change. For example, while the Minimalist Program's Merge is a simple formal operation (Berwick & Chomsky, 2016), the computational mechanisms required to implement the language it generates (e.g., to parse the language) may be considerably more complex. This has implications for the theory of grammar: theories of grammar which involve several kinds of syntactic operations may be no less evolutionarily plausible than a theory of grammar that involves only one. A deeper understanding of human language at the algorithmic and implementational levels could strengthen Minimalist Program's account of the evolution of language. PMID- 27368625 TI - The origins of language in teaching. AB - I introduce seven criteria for determining the validity of competing theories for the original function of language. I go on to present a novel explanation that meets all the criteria: language originally evolved to teach kin. I suggest that the use of symbols subsequently generated evolutionary feedback at two levels, in the form of self-modified selection pressures that favored structures in the mind that functioned to manipulate and use symbols with efficiency, and cultural selection on languages for learnability. PMID- 27368626 TI - Darwinian perspectives on the evolution of human languages. AB - Human languages evolve by a process of descent with modification in which parent languages give rise to daughter languages over time and in a manner that mimics the evolution of biological species. Descent with modification is just one of many parallels between biological and linguistic evolution that, taken together, offer up a Darwinian perspective on how languages evolve. Combined with statistical methods borrowed from evolutionary biology, this Darwinian perspective has brought new opportunities to the study of the evolution of human languages. These include the statistical inference of phylogenetic trees of languages, the study of how linguistic traits evolve over thousands of years of language change, the reconstruction of ancestral or proto-languages, and using language change to date historical events. PMID- 27368627 TI - Eliciting explanations: Constraints on when self-explanation aids learning. AB - Generating explanations for oneself in an attempt to make sense of new information (i.e., self-explanation) is often a powerful learning technique. Despite its general effectiveness, in a growing number of studies, prompting for self-explanation improved some aspects of learning, but reduced learning of other aspects. Drawing on this recent research, as well as on research comparing self explanation under different conditions, we propose four constraints on the effectiveness of self-explanation. First, self-explanation promotes attention to particular types of information, so it is better suited to promote particular learning outcomes in particular types of domains, such as transfer in domains guided by general principles or heuristics. Second, self-explaining a variety of types of information can improve learning, but explaining one's own solution methods or choices may reduce learning under certain conditions. Third, explanation prompts focus effort on particular aspects of the to-be-learned material, potentially drawing effort away from other important information. Explanation prompts must be carefully designed to align with target learning outcomes. Fourth, prompted self-explanation often promotes learning better than unguided studying, but alternative instructional techniques may be more effective under some conditions. Attention to these constraints should optimize the effectiveness of self-explanation as an instructional technique in future research and practice. PMID- 27368628 TI - The language-ready head: Evolutionary considerations. AB - This article offers a succinct overview of the hypothesis that the evolution of cognition could benefit from a close examination of brain changes reflected in the shape of the neurocranium. I provide both neurological and genetic evidence in support of this hypothesis, and conclude that the study of language evolution need not be regarded as a mystery. PMID- 27368629 TI - Using music to study the evolution of cognitive mechanisms relevant to language. AB - This article argues that music can be used in cross-species research to study the evolution of cognitive mechanisms relevant to spoken language. This is because music and language share certain cognitive processing mechanisms and because music offers specific advantages for cross-species research. Music has relatively simple building blocks (tones without semantic properties), yet these building blocks are combined into rich hierarchical structures that engage complex cognitive processing. I illustrate this point with regard to the processing of musical harmonic structure. Because the processing of musical harmonic structure has been shown to interact with linguistic syntactic processing in humans, it is of interest to know if other species can acquire implicit knowledge of harmonic structure through extended exposure to music during development (vs. through explicit training). I suggest that domestic dogs would be a good species to study in addressing this question. PMID- 27368630 TI - Laughter as an approach to vocal evolution: The bipedal theory. AB - Laughter is a simple, stereotyped, innate, human play vocalization that is ideal for the study of vocal evolution. The basic approach of describing the act of laughter and when we do it has revealed a variety of phenomena of social, linguistic, and neurological significance. Findings include the acoustic structure of laughter, the minimal voluntary control of laughter, the punctuation effect (which describes the placement of laughter in conversation and indicates the dominance of speech over laughter), and the role of laughter in human matching and mating. Especially notable is the use of laughter to discover why humans can speak and other apes cannot. Quadrupeds, including our primate ancestors, have a 1:1 relation between breathing and stride because their thorax must absorb forelimb impacts during running. The direct link between breathing and locomotion limits vocalizations to short, simple utterances, such as the characteristic panting chimpanzee laugh (one sound per inward or outward breath). The evolution of bipedal locomotion freed the respiration system of its support function during running, permitting greater breath control and the selection for human-type laughter (a parsed exhalation), and subsequently the virtuosic, sustained, expiratory vocalization of speech. This is the basis of the bipedal theory of speech evolution. PMID- 27368631 TI - Evolution of the neural language network. AB - The evolution of language correlates with distinct changes in the primate brain. The present article compares language-related brain regions and their white matter connectivity in the developing and mature human brain with the respective structures in the nonhuman primate brain. We will see that the functional specificity of the posterior portion of Broca's area (Brodmann area [BA 44]) and its dorsal fiber connection to the temporal cortex, shown to support the processing of structural hierarchy in humans, makes a crucial neural difference between the species. This neural circuit may thus be fundamental for the human syntactic capacity as the core of language. PMID- 27368632 TI - Assessing the uniqueness of language: Animal grammatical abilities take center stage. AB - Questions related to the uniqueness of language can only be addressed properly by referring to sound knowledge of the relevant cognitive abilities of nonhuman animals. A key question concerns the nature and extent of animal rule-learning abilities. I discuss two approaches used to assess these abilities. One is comparing the structures of animal vocalizations to linguistic ones, and another is addressing the grammatical rule- and pattern-learning abilities of animals through experiments using artificial grammars. Neither of these approaches has so far provided unambiguous evidence of advanced animal abilities. However, when we consider how animal vocalizations are analyzed, the types of stimuli and tasks that are used in artificial grammar learning experiments, the limited number of species examined, and the groups to which these belong, I argue that the currently available evidence is insufficient to arrive at firm conclusions concerning the limitations of animal grammatical abilities. As a consequence, the gap between human linguistic rule-learning abilities and those of nonhuman animals may be smaller and less clear than is currently assumed. This means that it is still an open question whether a difference in the rule-learning and rule abstraction abilities between animals and humans played the key role in the evolution of language. PMID- 27368633 TI - Linear grammar as a possible stepping-stone in the evolution of language. AB - We suggest that one way to approach the evolution of language is through reverse engineering: asking what components of the language faculty could have been useful in the absence of the full complement of components. We explore the possibilities offered by linear grammar, a form of language that lacks syntax and morphology altogether, and that structures its utterances through a direct mapping between semantics and phonology. A language with a linear grammar would have no syntactic categories or syntactic phrases, and therefore no syntactic recursion. It would also have no functional categories such as tense, agreement, and case inflection, and no derivational morphology. Such a language would still be capable of conveying certain semantic relations through word order-for instance by stipulating that agents should precede patients. However, many other semantic relations would have to be based on pragmatics and discourse context. We find evidence of linear grammar in a wide range of linguistic phenomena: pidgins, stages of late second language acquisition, home signs, village sign languages, language comprehension (even in fully syntactic languages), aphasia, and specific language impairment. We also find a full-blown language, Riau Indonesian, whose grammar is arguably close to a pure linear grammar. In addition, when subjects are asked to convey information through nonlinguistic gesture, their gestures make use of semantically based principles of linear ordering. Finally, some pockets of English grammar, notably compounds, can be characterized in terms of linear grammar. We conclude that linear grammar is a plausible evolutionary precursor of modern fully syntactic grammar, one that is still active in the human mind. PMID- 27368634 TI - Backward-walking biological motion orients attention to moving away instead of moving toward. AB - Walking direction is an important attribute of biological motion because it carries key information, such as the specific intention of the walker. Although it is known that spatial attention is guided by walking direction, it remains unclear whether this attentional shift is reflexive (i.e., constantly shifts to the walking direction) or not. A richer interpretation of this effect is that attention is guided to seek the information that is necessary to understand the motion. To investigate this issue, we examined how backward-walking biological motion orients attention because the intention of walking backward is usually to avoid something that walking forward would encounter. The results showed that attention was oriented to the walking-away direction of biological motion instead of the walking-toward direction (Experiment 1), and this effect was not due to the gaze direction of biological motion (Experiment 2). Our findings suggest that the attentional shift triggered by walking direction is not reflexive, thus providing support for the rich interpretation of these attentional effects. PMID- 27368635 TI - Toward the Language-Ready Brain: Biological Evolution and Primate Comparisons. AB - The approach to language evolution suggested here focuses on three questions: How did the human brain evolve so that humans can develop, use, and acquire languages? How can the evolutionary quest be informed by studying brain, behavior, and social interaction in monkeys, apes, and humans? How can computational modeling advance these studies? I hypothesize that the brain is language ready in that the earliest humans had protolanguages but not languages (i.e., communication systems endowed with rich and open-ended lexicons and grammars supporting a compositional semantics), and that it took cultural evolution to yield societies (a cultural constructed niche) in which language ready brains could become language-using brains. The mirror system hypothesis is a well-developed example of this approach, but I offer it here not as a closed theory but as an evolving framework for the development and analysis of conflicting subhypotheses in the hope of their eventual integration. I also stress that computational modeling helps us understand the evolving role of mirror neurons, not in and of themselves, but only in their interaction with systems "beyond the mirror." Because a theory of evolution needs a clear characterization of what it is that evolved, I also outline ideas for research in neurolinguistics to complement studies of the evolution of the language-ready brain. A clear challenge is to go beyond models of speech comprehension to include sign language and models of production, and to link language to visuomotor interaction with the physical and social world. PMID- 27368636 TI - Key cognitive preconditions for the evolution of language. AB - Languages are socially constructed systems of expression, generated interactively in social networks, which can be assimilated by the individual brain as it develops. Languages co-evolved with culture, reflecting the changing complexity of human culture as it acquired the properties of a distributed cognitive system. Two key preconditions set the stage for the evolution of such cultures: a very general ability to rehearse and refine skills (evident early in hominin evolution in toolmaking), and the emergence of material culture as an external (to the brain) memory record that could retain and accumulate knowledge across generations. The ability to practice and rehearse skill provided immediate survival-related benefits in that it expanded the physical powers of early hominins, but the same adaptation also provided the imaginative substrate for a system of "mimetic" expression, such as found in ritual and pantomime, and in proto-words, which performed an expressive function somewhat like the home signs of deaf non-signers. The hominid brain continued to adapt to the increasing importance and complexity of culture as human interactions with material culture became more complex; above all, this entailed a gradual expansion in the integrative systems of the brain, especially those involved in the metacognitive supervision of self-performances. This supported a style of embodied mimetic imagination that improved the coordination of shared activities such as fire tending, but also in rituals and reciprocal mimetic games. The time-depth of this mimetic adaptation, and its role in both the construction and acquisition of languages, explains the importance of mimetic expression in the media, religion, and politics. Spoken language evolved out of voco-mimesis, and emerged long after the more basic abilities needed to refine skill and share intentions, probably coinciding with the common ancestor of sapient humans. Self-monitoring and self supervised practice were necessary preconditions for lexical invention, and as these abilities evolved further, communicative skills extended to more abstract and complex aspects of the communication environments-that is, the "cognitive ecologies"-being generated by human groups. The hominin brain adapted continuously to the need to assimilate language and its many cognitive byproducts by expanding many of its higher integrative systems, a process that seems to have accelerated and peaked in the past half million years. PMID- 27368638 TI - The language capacity: architecture and evolution. AB - There is substantial evidence that the human language capacity (LC) is a species specific biological property, essentially unique to humans, invariant among human groups, and dissociated from other cognitive systems. Each language, an instantiation of LC, consists of a generative procedure that yields a discrete infinity of hierarchically structured expressions with semantic interpretations, hence a kind of "language of thought" (LOT), along with an operation of externalization (EXT) to some sensory-motor system, typically sound. There is mounting evidence that generation of LOT observes language-independent principles of computational efficiency and is based on the simplest computational operations, and that EXT is an ancillary process not entering into the core semantic properties of LOT and is the primary locus of the apparent complexity, diversity, and mutability of language. These conclusions are not surprising, since the internal system is acquired virtually without evidence in fundamental respects, and EXT relates it to sensory-motor systems that are unrelated to it. Even such properties as the linear order of words appear to be reflexes of the sensory motor system, not available to generation of LOT. The limited evidence from the evolutionary record lends support to these conclusions, suggesting that LC emerged with Homo sapiens or not long after, and has not evolved since human groups dispersed. PMID- 27368637 TI - A cortical circuit for voluntary laryngeal control: Implications for the evolution language. AB - The development of voluntary laryngeal control has been argued to be a key innovation in the evolution of language. Part of the evidence for this hypothesis comes from neuroscience. For example, comparative research has shown that humans have direct cortical innervation of motor neurons controlling the larynx, whereas nonhuman primates do not. Research on cortical motor control circuits has shown that the frontal lobe cortical motor system does not work alone; it is dependent on sensory feedback control circuits. Thus, the human brain must have evolved not only the required efferent motor pathway but also the cortical circuit for controlling those efferent signals. To fill this gap, I propose a link between the evolution of laryngeal control and neuroscience research on the human dorsal auditory-motor speech stream. Specifically, I argue that the dorsal stream Spt (Sylvian parietal-temporal) circuit evolved in step with the direct cortico laryngeal control pathway and together represented a key advance in the evolution of speech. I suggest that a cortical laryngeal control circuit may play an important role in language by providing a prosodic frame for speech planning. PMID- 27368639 TI - Animal language studies: What happened? AB - The extent to which nonhuman animals can learn actual human language is a controversial question, but many nonhuman species have acquired elements of a two way communication system that is, and was, sophisticated enough to enable its use in evaluating cognitive capacities. This article is a personal view of the history of these animal language studies. PMID- 27368640 TI - Being low prepares for being neglected: Verticality affects expectancy of social participation. AB - Previous research suggests that the established link of vertical position and self-assignment of social power affects the processing of social exclusion. We hypothesized that verticality-induced self-assignment of social power moderates the evaluation of exclusion via a change in subjective expectancy of social participation. Following this idea, a superior position-associated with higher power-was supposed to increase the sensitivity for a transition to social exclusion. The transition was simulated in a virtual ball tossing game (cyberball): an inclusionary block was followed by partial exclusion of the participant. The participants' vertical position relative to the co-players was varied in three experimental groups (superior vs. even vs. inferior). From inclusion to partial exclusion, we observed an increase of an event-related brain potential related to the violation of subjective expectancy (P3), and participants reported a corresponding increase in threat to social needs and negative mood. For participants at inferior position exclusionary effects on both, P3 and need threat, were less pronounced as compared to participants at even or superior position. These results indicate that verticality impacts basic cognitive processes of subjective expectancy formation. An inferior position already provides a bias for the loss of social power, and the transition to social exclusion is less unexpected. PMID- 27368641 TI - What the hands can tell us about language emergence. AB - Why, in all cultures in which hearing is possible, has language become the province of speech and the oral modality? I address this question by widening the lens with which we look at language to include the manual modality. I suggest that human communication is most effective when it makes use of two types of formats--a discrete and segmented code, produced simultaneously along with an analog and mimetic code. The segmented code is supported by both the oral and the manual modalities. However, the mimetic code is more easily handled by the manual modality. We might then expect mimetic encoding to be done preferentially in the manual modality (gesture), leaving segmented encoding to the oral modality (speech). This argument rests on two assumptions: (1) The manual modality is as good at segmented encoding as the oral modality; sign languages, established and idiosyncratic, provide evidence for this assumption. (2) Mimetic encoding is important to human communication and best handled by the manual modality; co speech gesture provides evidence for this assumption. By including the manual modality in two contexts--when it takes on the primary function of communication (sign language), and when it takes on a complementary communicative function (gesture)--in our analysis of language, we gain new perspectives on the origins and continuing development of language. PMID- 27368644 TI - [Not Available]. PMID- 27368645 TI - [Not Available]. PMID- 27368643 TI - The Culture of Academic Medicine: Faculty Behaviors Impacting the Learning Environment. AB - OBJECTIVE: The culture of academic medical institutions impacts trainee education, among many other faculty and patient outcomes. Disrespectful behavior by faculty is one of the most challenging and common problems that, left unattended, disrupts healthy work and learning environments. Conversely, a respectful environment facilitates learning, creates a sense of safety, and rewards professionalism. The authors developed surveys and an intervention in an effort to better understand and improve climate concerns among health sciences faculty at the University of California, San Diego (UCSD), a research-intense, public, academic medical center. METHODS: An online "climate survey" of all UC San Diego health sciences faculty was conducted in 2011-2012. A strategic campaign to address the behavioral issues identified in the initial survey was subsequently launched. In 2015, the climate was re-evaluated in order to assess the effectiveness of the intervention. RESULTS: A total of 478 faculty members (223 women, 235 men, 35 % of faculty) completed the baseline survey, reporting relatively low levels of observed sexual harassment (7 %). However, faculty reported concerning rates of other disruptive behaviors: derogatory comments (29 %), anger outbursts (25 %), and hostile communication (25 %). Women and mid-level faculty were more likely to report these behavioral concerns than men and junior or senior colleagues. Three years after an institutional strategy was initiated, 729 faculty members (50 % of the faculty) completed a follow-up survey. The 2015 survey results indicate significant improvement in numerous climate factors, including overall respectful behaviors, as well as behaviors related to gender. CONCLUSIONS: In order to enhance a culture of respect in the learning environment, institutions can effectively engage academic leaders and faculty at all levels to address disruptive behavior and enhance positive climate factors. PMID- 27368642 TI - CRISPR-Cas9-mediated efficient directed mutagenesis and RAD51-dependent and RAD51 independent gene targeting in the moss Physcomitrella patens. AB - The ability to address the CRISPR-Cas9 nuclease complex to any target DNA using customizable single-guide RNAs has now permitted genome engineering in many species. Here, we report its first successful use in a nonvascular plant, the moss Physcomitrella patens. Single-guide RNAs (sgRNAs) were designed to target an endogenous reporter gene, PpAPT, whose inactivation confers resistance to 2 fluoroadenine. Transformation of moss protoplasts with these sgRNAs and the Cas9 coding sequence from Streptococcus pyogenes triggered mutagenesis at the PpAPT target in about 2% of the regenerated plants. Mainly, deletions were observed, most of them resulting from alternative end-joining (alt-EJ)-driven repair. We further demonstrate that, in the presence of a donor DNA sharing sequence homology with the PpAPT gene, most transgene integration events occur by homology driven repair (HDR) at the target locus but also that Cas9-induced double-strand breaks are repaired with almost equal frequencies by mutagenic illegitimate recombination. Finally, we establish that a significant fraction of HDR-mediated gene targeting events (30%) is still possible in the absence of PpRAD51 protein, indicating that CRISPR-induced HDR is only partially mediated by the classical homologous recombination pathway. PMID- 27368646 TI - [Not Available]. PMID- 27368647 TI - [Not Available]. PMID- 27368648 TI - [Not Available]. PMID- 27368649 TI - [Not Available]. PMID- 27368651 TI - [Not Available]. PMID- 27368650 TI - [Not Available]. PMID- 27368652 TI - [Not Available]. PMID- 27368654 TI - [Not Available]. PMID- 27368653 TI - [Not Available]. PMID- 27368655 TI - [Not Available]. PMID- 27368657 TI - [Not Available]. PMID- 27368656 TI - [Not Available]. PMID- 27368658 TI - [Not Available]. PMID- 27368659 TI - [Not Available]. PMID- 27368661 TI - [Not Available]. PMID- 27368660 TI - [Not Available]. PMID- 27368662 TI - [Not Available]. PMID- 27368664 TI - [Not Available]. PMID- 27368663 TI - [Not Available]. PMID- 27368665 TI - [Not Available]. PMID- 27368666 TI - [Not Available]. PMID- 27368667 TI - [Not Available]. PMID- 27368668 TI - [Not Available]. PMID- 27368669 TI - [Not Available]. PMID- 27368670 TI - [Not Available]. PMID- 27368671 TI - Successful treatment of refractory giant cell arteritis with etanercept. PMID- 27368674 TI - [Not Available]. PMID- 27368673 TI - [Not Available]. PMID- 27368672 TI - A phase 1 study of the safety, tolerability, pharmacodynamics, and pharmacokinetics of tenapanor in healthy Japanese volunteers. AB - BACKGROUND: Tenapanor (RDX5791, AZD1722), a small molecule with minimal systemic availability, is an inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3). Tenapanor acts locally in the gut to reduce absorption of sodium and phosphate. It is being developed for the treatment of patients with hyperphosphatemia in CKD requiring dialysis and patients with constipation-predominant irritable bowel syndrome. We report the safety, pharmacodynamics, and pharmacokinetics of tenapanor in Japanese volunteers. METHODS: In this phase 1, double-blind study (NCT02176252), healthy Japanese adults (aged 20-45 years) received single-dose tenapanor 180 mg (n = 6), repeated-dose tenapanor 15, 30, 60, or 90 mg twice daily (n = 12 each) for 7 days, or placebo (n = 14). All participants received a standardized diet. RESULTS: Single and repeated doses of tenapanor resulted in higher mean stool sodium content vs. placebo (single dose, 41.9 mmol/day; repeated dose, range of means 21.3-32.2 mmol/day; placebo, 4.1 mmol/day) accompanied by lower urinary sodium content (single dose, 110 mmol/day; repeated dose, 101-112 mmol/day; placebo, 143 mmol/day). Additionally, stool phosphorus content was increased (single dose, 31.0 mmol/day; repeated dose, 17.6-24.8 mmol/day; placebo, 16.8 mmol/day) and urinary phosphorus content decreased (single dose, 18.7 mmol/day; repeated dose, 15.3-19.4 mmol/day; placebo, 25.5 mmol/day). Tenapanor had minimal systemic exposure, provided a softer stool consistency, and was well tolerated. CONCLUSIONS: Tenapanor treatment reduced absorption of intestinal sodium and phosphate from the gut in Japanese adults. Tenapanor had minimal systemic exposure and was well tolerated. Further research into the clinical benefits of tenapanor is warranted. PMID- 27368675 TI - [Not Available]. PMID- 27368676 TI - [Not Available]. PMID- 27368677 TI - [Not Available]. PMID- 27368678 TI - [Not Available]. PMID- 27368679 TI - [Not Available]. PMID- 27368680 TI - [Not Available]. PMID- 27368681 TI - [Not Available]. PMID- 27368682 TI - [Not Available]. PMID- 27368683 TI - [Not Available]. PMID- 27368684 TI - [Not Available]. PMID- 27368685 TI - [Not Available]. PMID- 27368686 TI - [Not Available]. PMID- 27368687 TI - [Not Available]. PMID- 27368688 TI - [Not Available]. PMID- 27368689 TI - [Not Available]. PMID- 27368690 TI - [Not Available]. PMID- 27368691 TI - [Not Available]. PMID- 27368692 TI - [Not Available]. PMID- 27368693 TI - [Not Available]. PMID- 27368694 TI - [Not Available]. PMID- 27368696 TI - Mass Spectrometry-Based Diagnosis of Hemoglobinopathies: A Potential Tool for the Screening of Genetic Disorder. AB - Hemoglobinopathies are caused by point mutation in globin gene that results in structural variant of hemoglobin. While 7 % of world populations are carrier of hemoglobinopathies, the prevalence of the disease varies between 3 to 17 % across different population groups in India. In a diagnostic laboratory, alkaline gel electrophoresis and cation exchange-based HPLC (CE-HPLC) are most widely used techniques for characterization of hemoglobin variants. In the above methods, the differential surface charge of hemoglobin molecule in variants is exploited for their characterization. Sometime, co-migration of variants in gel electrophoresis and co-elution or elution with unknown retention time in automated CE-HPLC might lead to ambiguity in the analysis of hemoglobinopathies. Under such circumstances, it is necessary to use other analytical methods that provide unambiguous results. Mass spectrometry-based proteomics approach and DNA sequence analysis are examples of such alternative methods. In the present study, liquid chromatography coupled to mass spectrometry has been used for three commonly observed variants in India, e.g., HbE, HbQ India and HbD Punjab that appeared with inappropriate results in the conventional analysis. A customized hemoglobin variant database has been used in the mass spectrometry-based analysis of those three variants. Mass spectrometry-based proteomics approach was used to analyze above variant sample accurately. PMID- 27368695 TI - Exercise echocardiography for the assessment of pulmonary hypertension in systemic sclerosis: a systematic review. AB - BACKGROUND: Pulmonary arterial hypertension (PAH) complicates the course of systemic sclerosis (SSc) and is associated with poor prognosis. The elevation of systolic pulmonary arterial pressure (sPAP) during exercise in patients with SSc with normal resting haemodynamics may anticipate the development of PAH. Exercise echocardiography (ExEcho) has been proposed as a useful technique to identify exercise-induced increases in sPAP, but it is unclear how to clinically interpret these findings. In this systematic review, we summarize the available evidence on the role of exercise echocardiography to estimate exercise-induced elevations in pulmonary and left heart filling pressures in patients with systemic sclerosis. METHODS: We conducted a systematic review of the literature using MEDLINE, Cochrane Library and Web of Knowledge, using the vocabulary terms: ('systemic sclerosis' OR 'scleroderma') AND ('exercise echocardiography') AND ('pulmonary hypertension'). Studies including patients with SSc without a prior diagnosis of PAH, and subjected to exercise echocardiography were included. All searches were limited to English and were augmented by review of bibliographic references from the included studies. The quality of evidence was assessed by the Effective Public Health Practice Project system. RESULTS: We identified 15 studies enrolling 1242 patients, who were mostly middle-aged and female. Several exercise methods were used (cycloergometer, treadmill and Master's two step), with different protocols and positions (supine, semi-supine, upright); definition of a positive test also varied widely. Resting estimated sPAP levels varied from 18 to 35 mm Hg, all in the normal range. The weighted means for estimated sPAP were 22.2 +/- 2.9 mmHg at rest and 43.0 +/- 4.3 mmHg on exercise; more than half of the studies reported mean exercise sPAP >=40 mmHg. The assessment of left ventricular diastolic function on peak exercise was reported in a minority of studies; however, when assessed, surrogate variables of left ventricular (LV) diastolic dysfunction were associated with higher sPAP on exercise. CONCLUSIONS: We found very high heterogeneity in the methods, the protocols and the estimated sPAP response to exercise. LV diastolic dysfunction was common and was associated with greater elevation of sPAP on exercise. PMID- 27368697 TI - Glutathione S-Transferase Pi-Ile 105 Val Polymorphism and Susceptibility to T2DM in Population from Turabah Region of Saudi Arabia. AB - Type 2 diabetes mellitus is characterized by chronic hyperglycemia and associated with oxidative stress resulting from accumulation of free radicals in body's tissues, which especially affects beta cells in pancreas and is an important factor in the development of diabetes and its complications. Glutathione S transferases (GSTs) are a family of antioxidant enzymes that play important roles in decreasing ROS species and act as a kind of antioxidant defense. In a case control study, we investigated the role of GSTP1 Ile105Val polymorphism in predisposition to T2DM in patients from Tarabah province, Saudi Arabia. The polymorphism was screened by PCR-RFLP in 90 T2DM patients and 87 healthy controls. The genotypes and alleles frequencies in cases and controls were assessed using Cochran-Armitage trend test and odds ratios (ORs), and 95 % confidence intervals (CIs) in different genetic models of inheritance were calculated. Our data indicate that G allele (Val) is associated with an increased risk for T2DM in this population in any combination (OR 4.101, 95 % CI 1.986 8.469, P = 0.00008). This indicates that individuals who are carriers for the mutant allele, either in homozygous (GG) or heterozygous (AG) state, are at fourfold higher risk for development of T2DM than other subjects in this population. PMID- 27368698 TI - Comparative genomics reveals multiple pathways to mutualism for tick-borne pathogens. AB - BACKGROUND: Multiple important human and livestock pathogens employ ticks as their primary host vectors. It is not currently known whether this means of infecting a host arose once or many times during evolution. RESULTS: In order to address this question, we conducted a comparative genomics analysis on a set of bacterial pathogens from seven genera - Borrelia, Rickettsia, Anaplasma, Ehrlichia, Francisella, Coxiella, and Bartonella, including species from three different host vectors - ticks, lice, and fleas. The final set of 102 genomes used in the study encoded a total of 120,046 protein sequences. We found that no genes or metabolic pathways were present in all tick-borne bacteria. However, we found some genes and pathways were present in subsets of tick-transmitted organisms while absent from bacteria transmitted by lice or fleas. CONCLUSION: Our analysis suggests that the ability of pathogens to be transmitted by ticks arose multiple times over the course of evolution. To our knowledge, this is the most comprehensive study of tick transmissibility to date. PMID- 27368699 TI - The impact of a standardized order set for the management of non-hip fragility fractures in a Fracture Liaison Service. AB - : We analysed the impact of a standardized order set empowering staff nurses to independently manage a Fracture Liaison Service over a 9-month period. Nurses identified between 30 and 70 % of non-hip fragility fractures to the unit in charge of management over time. The latter managed 58 % of referred patients. INTRODUCTION: The main goal of this study was to evaluate the impact of a standardized order set empowering nurses to independently manage a fracture liaison service (FLS). METHODS: Since November 2014, an order set allowed nurses of a Montreal hospital, Quebec, Canada to entirely manage an FLS on their own. Nurses followed an 6-h training program on-site. Emergency department (ED) and orthopaedic outpatient clinic (OC) nurses identified non-hip fragility fractures. Medical day treatment unit (MDTU) nurses were in charge of the management (investigation and treatment initiation). The list of patients, 50 years and older, with a fracture were retrieved for the period of November 2014 to July 2015. Performance was assessed with the rate of identification over time and the rate of management of non-hip fragility fractures. RESULTS: Over the 9-month period, 346 patients of >=50 years old were seen for a fracture, of which 190 met fragility criteria (excluding hip fractures). A sinusoid pattern of rates of identification between 30-70 % was observed over time. An average proportion of 58.1 % of fracture patients were managed by MDTU nurses. CONCLUSIONS: A standardized order set legally allowing nurses to manage an FLS led to identification rates varying from 30-70 % and a management rate close to 60 % for referred patients over a 9-month period, which largely exceeds that of standard care. Identification was mostly compromised by difficulty integrating the order set into routine practice. Enforcement of the hospital policy on fragility fractures could help yield efficiency of identification of osteoporosis-related fractures by the staff. PMID- 27368700 TI - Antibacterial constituents of Fructus Chebulae Immaturus and their mechanisms of action. AB - BACKGROUND: To extract, purify, and identify the effective constituents of aqueous extract of Fructus Chebulae Immaturus, and analyze the bactericidal effects of total tannins. METHODS: Preparative thin layer chromatography and semi preparative high performance liquid chromatography were used to isolate and purify the total tannin fraction. (1)H- and (13)C- NMR spectroscopy were used to elucidate compound structures. The antibacterial activities of total tannins and ethyl gallate on Klebsiella pneumoniae (KP) and Staphylococcus aureus (SA) were determined through minimum inhibitory concentration and minimum bactericidal concentration assays. Their antibacterial mechanisms of action were explored by transmission electron microscopy and scanning electron microscopy. RESULTS: Five compounds were isolated: ellagic acid, ethyl gallate, arjugenin, beta-sitosterol, and tri-n-butyl chebulate. Tri-n-butyl chebulate is a newly-reported compound. Total tannins and ethyl gallate both had favorable bactericidal effects against KP and SA. CONCLUSION: In vivo and in vitro pharmacodynamic experiment demonstrated that the effective components of Fructus Chebulae Immaturus possessed significant antibacterial effects, and were nontoxic and safe. TRIAL REGISTRATION: No results of a health care intervention on human participants. PMID- 27368702 TI - [Not Available]. PMID- 27368703 TI - [Not Available]. PMID- 27368701 TI - Late morphological changes after radiosurgery of brain arteriovenous malformations: an MRI study. AB - BACKGROUND: Radiosurgery by Gamma Knife (GK) is an effective treatment for brain arteriovenous malformations (AVM). The aim of the present study was to evaluate late, radiation-induced changes detectable by MRI after AVM radiosurgery in patients treated minimally 10 years prior, with AVM obliteration proven by angiography. METHODS: Thirty-five patients with 37 AVMs were included. AVMs were irradiated 16.6 +/- 3.5 years prior with AVM obliteration proven 13 +/- 4 years prior. All patients underwent recent MRI examinations, including application of gadolinium-based contrast. RESULTS: In one case, post-irradiative cystic formation with mass effect and signs of hemorrhage requiring surgery was found. Post-gadolinium enhancement at the site of obliterated nidi was apparent in 28 of 37 cases (76 %). In all cases except one, the mean volume of enhancement at the time of review was clearly lower than the volume of the originally irradiated AVM (88 +/- 20 %; median 92 %); in one case the extent was 142 % greater than the irradiated AVM. When we compared enhancing and non-enhancing nidi, we found that enhancing nidi were significantly larger than non-enhancing nidi at the time of radiosurgery (4.39 +/- 3.35 cc vs. 0.89 +/- 0.79 cc, p = 0.004). Enhancement was not influenced by total radiation dose, patient age at the time of irradiation, duration since radiosurgery, or the number of irradiations. Wallerian degeneration was found in nine of 37 cases (24 %); in six cases the optical tracts were affected and visual field defects were proven. In five of nine cases (55.6 %) with Wallerian degeneration previous hemorrhage was present. Dual vascular pathology was found in eight of 35 patients (23 %). CONCLUSIONS: GK radiosurgery for AVM is a safe treatment method although delayed complications may occur. Post-gadolinium enhancement of obliterated nidi may indicate an active post-irradiative process. PMID- 27368704 TI - [Not Available]. PMID- 27368705 TI - [Not Available]. PMID- 27368706 TI - [Not Available]. PMID- 27368707 TI - [Not Available]. PMID- 27368708 TI - [Not Available]. PMID- 27368710 TI - Echocardiographic effects of dexmedetomidine-ketamine in chinchillas ( Chinchilla lanigera). AB - Alpha2-agonist anesthetic combinations are often used in rodent anesthesia but no information about their effects on cardiac function in chinchillas exists. The purpose of this study was to utilize echocardiography to evaluate the cardiovascular effects of dexmedetomidine-ketamine anesthesia in chinchillas. Echocardiographic examinations were performed in eight adult chinchillas under manual restraint and following dexmedetomidine (0.015 mg/kg) and ketamine (4 mg/kg) administration. Dexmedetomidine-ketamine anesthesia resulted in a significantly decreased heart rate, fractional shortening, cardiac output, and flow velocity across the aortic and pulmonic valves, and significantly increased left ventricular internal diameter in systole. The observed changes in echocardiographic parameters are similar to those previously reported in chinchillas anesthetized with isoflurane. PMID- 27368709 TI - The gut microbiome of the sea urchin, Lytechinus variegatus, from its natural habitat demonstrates selective attributes of microbial taxa and predictive metabolic profiles. AB - In this paper, we describe the microbial composition and their predictive metabolic profile in the sea urchin Lytechinus variegatus gut ecosystem along with samples from its habitat by using NextGen amplicon sequencing and downstream bioinformatics analyses. The microbial communities of the gut tissue revealed a near-exclusive abundance of Campylobacteraceae, whereas the pharynx tissue consisted of Tenericutes, followed by Gamma-, Alpha- and Epsilonproteobacteria at approximately equal capacities. The gut digesta and egested fecal pellets exhibited a microbial profile comprised of Gammaproteobacteria, mainly Vibrio, and Bacteroidetes. Both the seagrass and surrounding sea water revealed Alpha- and Betaproteobacteria. Bray-Curtis distances of microbial communities indicated a clustering profile with low intrasample variation. Predictive metagenomics performed on the microbial communities revealed that the gut tissue had high relative abundances of metabolisms assigned to the KEGG-Level-2 designation of energy metabolisms compared to the gut digesta, which had higher carbohydrate, amino acid and lipid metabolisms. Overall, the results of this study elaborate the spatial distribution of microbial communities in the gut ecosystem of L. variegatus, and specifically a selective attribute for Campylobacteraceae in the gut tissue. Also, the predictive functional significance of bacterial communities in uniquely compartmentalized gut ecosystems of L. variegatus has been described. PMID- 27368711 TI - Rapid conditional targeted ablation model for hemolytic anemia in the rat. AB - Effective methods for cell ablation are important tools for examining the anatomical, functional, and behavioral consequences of selective loss of specific cell types in animal models. We have developed an ablation system based on creating genetically modified animals that express human CD59 (hCD59), a membrane receptor, and administering intermedilysin (ILY), a toxin produced by Streptococcus intermedius, which binds specifically to hCD59 to induce cell lysis. As proof-of-concept in the rat, we generated an anemia model, SD-Tg(CD59 HBA1)Bryd, which expresses hCD59 on erythrocytes. Hemolysis is a common complication of inherited or acquired blood disorders, which can result in cardiovascular compromise and death. A rat model that can replicate hemolysis through specific ablation of erythrocytes would allow further study of disease and novel treatments. In vitro, complete lysis of erythrocytes expressing hCD59 was observed at and above 250 pM ILY, while no lysis was observed in wild-type erythrocytes at any ILY concentration (8-1,000 pM). In vivo, ILY intravenous injection (100 ng/g body wt) dramatically reduced the hematocrit within 10 min, with a mean hematocrit reduction of 43% compared with 1.4% in the saline control group. Rats injected with ILY at 500 ng/g intraperitoneally developed gross signs of anemia. Histopathology confirmed anemia and revealed hepatic necrosis, with microthrombi present. These studies validate the hCD59-ILY cell ablation technology in the rat and provide the scientific community with a new rapid conditional targeted ablation model for hemolytic anemia and hemolysis-associated sequelae. PMID- 27368712 TI - Young voices in mental health care: Exploring children's and adolescents' service experiences and preferences. AB - The development of 'youth-friendly' services has become a priority across a wide range of health-care contexts. However, relatively few studies have specifically examined users' experiences of, and preferences for, child and adolescent mental health care. The current study investigated young service users' views of outpatient and community mental health clinics in Sweden, based on two data sources. First, focus group interviews were conducted with seven children and adolescents (aged 10-18 years) to explore both positive and negative experiences of mental health care. Second, written suggestions about specific service improvements were obtained from 106 children and adolescents. Qualitative content analysis revealed three overarching themes: 'Accessibility', 'Being heard and seen' and 'Usefulness of sessions'. Young people's recommendations for improving practice included more convenient appointment times, offered in welcoming settings; opportunities to communicate more openly with clinical staff, enabling sensitive discussion of mental health and wider personal issues; and more structured treatments that offer greater credibility and relevance to young people's mental health and developmental needs. Young people also discussed being compelled by parents and school professionals to engage in treatment. Attending to young people's preferences must be a priority in order to overcome ambivalence about session attendance, and enhance treatment participation and outcomes. PMID- 27368713 TI - Scorpion envenoming caused by Tityus cf. silvestris evolving with severe muscle spasms in the Brazilian Amazon. AB - Scorpion stings are a public health problem in the Brazilian Amazon. However, detailed clinical characterization with the proper animal identification is scarce. Here we report a confirmed case of envenoming by Tityus cf. silvestris in the Brazilian Amazon. The case evolved with generalized muscle spasms and was treated with antivenom and supportive therapy, requiring intensive care unit admission. The patient evolved favourably and was discharged after 9 days of hospitalization. PMID- 27368714 TI - Febrile ulceronecrotic Mucha-Habermann disease in an 8-year-old boy responding to methotrexate. AB - BACKGROUND: Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare fulminant variant of pityriasis lichenoides et varioliformis acuta (PLEVA) characterized by a rapidly progressive course with predominant ulceronecrotic lesions associated with fever and systemic manifestations. First described by Degos in 1966, it carries a high morbidity and is potentially fatal. The exact pathogenesis is not clear, but it is proposed to be the result of hypersensitivity reaction to an infection. METHODS: Here we report the case of an 8-year-old boy with FUMHD in the eastern province of Saudi Arabia. RESULTS: The patient presented with pyrexia, fatigue, arthralgia, and worsening of his already existing skin lesions of PLEVA. There was an extensive painful erythematous maculopapular rash, some lesions ulcerated and necrotic, involving the face, trunk, limbs, and flexures. A diagnosis of FUMHD was made based on clinical and histological features. The skin lesions responded extremely well to oral methotrexate, with almost complete healing after 4 weeks. CONCLUSIONS: We describe a rare variant of PLEVA, namely FUMHD, in an 8-year-old boy who showed a remarkably favorable response to methotrexate, as manifested by near total clearance of the skin lesions without scarring or hyperpigmentation. PMID- 27368715 TI - Induction of delayed wound healing by irradiation with optional mechanical compression in swine. AB - A chronic wound or non-healing wound is one that fails to heal for at least 30 days after injury. This study was designed to create delayed wound healing induced by irradiation and mechanical compression using silicone block. Two female pigs received a single fraction of 20 Gy with 6-MeV electrons to a 22 * 60 cm field on the dorsal body skin 7 weeks before experimentation. A 30 * 30 mm sized wounds were created with preservation of muscle fascia on the dorsum. In groups of six, wounds were designated to be control (C) or test areas of irradiation only (T0), irradiation with silicone blocks for 1 week (T1), irradiation with silicone blocks for 2 weeks (T2), and irradiation with silicone blocks for 3 weeks (T3). Wound contraction, bacterial culture, and histological analysis were performed at 1-week intervals for 4 weeks. Control wounds displayed complete re-epithelialization at Weeks 4; however, all experimental groups (T0, T1, T2, and T3 groups) showed necrosis and delayed healing at Week 4. The number of bacterial strains in control wounds differed significantly from values recorded for all experimental groups from Weeks 1-3 (p < 0.05). However, in comparing the various test wounds (T0, T1, T2, and T3 groups), the numbers of strains did not differ significantly from Weeks 1-4. In the histological analysis, the control wound showed a peak influx of acute and chronic inflammatory cell and diminished inflammation thereafter. However, all experimental groups showed no peak in inflammatory score and prolonged chronic inflammation. In conclusion, radiation exposure alone, which triggers intense inflammation and extensive recruitment of inflammatory cells, proved sufficient to prevent re-epithelialization of skin at 30 days. Insertion of silicone blocks had limited effects on promoting delayed wound healing. Consequently, we now recommend using irradiation alone to simulate delayed wound healing in an experimental setting. PMID- 27368718 TI - [Not Available]. PMID- 27368719 TI - [Not Available]. PMID- 27368717 TI - First depressed, then discriminated against? AB - Each year a substantial share of the European population suffers from major depression. This mental illness may affect individuals' later life outcomes indirectly by the stigma it inflicts. The present study assesses hiring discrimination based on disclosed depression. To this end, between May 2015 and July 2015, we sent out 288 trios of job applications from fictitious candidates to real vacancies in Belgium. Within each trio, one candidate claimed to have become unemployed only recently, whereas the other two candidates revealed former depression or no reason at all for their unemployment during a full year. Disclosing a year of inactivity due to former depression decreases the probability of getting a job interview invitation by about 34% when compared with candidates who just became unemployed, but the stigma effect of a year of depression is not significantly higher than the stigma effect of a year of unexplained unemployment. In addition, we found that these stigmas of depression and unemployment were driven by our male trios of fictitious candidates. As a consequence, our results are in favour of further research on gender heterogeneity in the stigma of depression and other health impairments. PMID- 27368720 TI - [Not Available]. PMID- 27368721 TI - [Not Available]. PMID- 27368722 TI - [Not Available]. PMID- 27368716 TI - Stress-related skin disorders. AB - Emerging research has suggested that the skin is not only a target of organismal distress but also an active participant of the stress response through production of local "HPA axis" components, peripheral nerve endings, and resident skin cells, including keratinocytes, mast cells, and immune/immune accessory cells. There are also bidirectional communication pathways between the brain and the skin, which play significant roles in integrating these interactions. In this review, we summarize the intricate relations between stress and several skin conditions. We have tried to identify the underlying mechanisms that link stress to the common dermatoses according to the latest scientific findings. PMID- 27368723 TI - [Not Available]. PMID- 27368724 TI - [Not Available]. PMID- 27368725 TI - [Not Available]. PMID- 27368726 TI - [Not Available]. PMID- 27368727 TI - [Not Available]. PMID- 27368728 TI - [Not Available]. PMID- 27368729 TI - [Not Available]. PMID- 27368730 TI - [Not Available]. PMID- 27368732 TI - [Not Available]. PMID- 27368731 TI - [Not Available]. PMID- 27368733 TI - [Not Available]. PMID- 27368734 TI - [Not Available]. PMID- 27368735 TI - [Not Available]. PMID- 27368736 TI - [Not Available]. PMID- 27368737 TI - [Not Available]. PMID- 27368738 TI - Biological devulcanization of ground natural rubber by Gordonia desulfuricans DSM 44462(T) strain. AB - Due to the rapid increase of waste vulcanized rubber products, the development of low-cost, efficient, and selective devulcanization processes is needed. In this paper, the devulcanization ability of Gordonia desulfuricans DSM 44462(T) was evaluated by a design of experiments. The aim of the experimental design was to investigate the importance of parameters influencing the bacterial growth, such as the glucose concentration (C), dibenzothiophene concentration (DBT), and initial biomass (optical density, OD) in biodevulcanization process. The complex viscosity (eta*) was chosen as experimental response for the experimental design. A multiple linear regression was used to model the relationship between the response and the process variables. In addition, the crosslink density and gel fraction were measured. Furthermore, the automated ribosomal intergenic spacer analysis (ARISA) as a microbiological method was performed to assess the persistence of the inoculated strain during the experiments. Reduced regression models were obtained considering only the significant variables and interactions. The glucose concentration C and OD variables and C-DBT and DBT-OD interactions resulted to the relevant parameters for the process. The fingerprinting showed the persistence of G. desulfuricans DSM 44462(T), despite the presence of other bacterial population after the VGNR sterilization. These results highlight the importance to support the physics analysis with microbiological analyses to evaluate the bacterial persistence during the treatment. PMID- 27368739 TI - X-ray structures of the Pseudomonas cichorii D-tagatose 3-epimerase mutant form C66S recognizing deoxy sugars as substrates. AB - Pseudomonas cichorii D-tagatose 3-epimerase (PcDTE), which has a broad substrate specificity, efficiently catalyzes the epimerization of not only D-tagatose to D sorbose but also D-fructose to D-psicose (D-allulose) and also recognizes the deoxy sugars as substrates. In an attempt to elucidate the substrate recognition and catalytic reaction mechanisms of PcDTE for deoxy sugars, the X-ray structures of the PcDTE mutant form with the replacement of Cys66 by Ser (PcDTE_C66S) in complexes with deoxy sugars were determined. These X-ray structures showed that substrate recognition by the enzyme at the 1-, 2-, and 3-positions is responsible for enzymatic activity and that substrate-enzyme interactions at the 4-, 5-, and 6-positions are not essential for the catalytic reaction of the enzyme leading to the broad substrate specificity of PcDTE. They also showed that the epimerization site of 1-deoxy 3-keto D-galactitol is shifted from C3 to C4 and that 1-deoxy sugars may bind to the catalytic site in the inhibitor-binding mode. The hydrophobic groove that acts as an accessible surface for substrate binding is formed through the dimerization of PcDTE. In PcDTE_C66S/deoxy sugar complex structures, bound ligand molecules in both the linear and ring forms were detected in the hydrophobic groove, while bound ligand molecules in the catalytic site were in the linear form. This result suggests that the sugar-ring opening of a substrate may occur in the hydrophobic groove and also that the narrow channel of the passageway to the catalytic site allows a substrate in the linear form to pass through. PMID- 27368740 TI - The diversity and distribution of anammox bacteria in the marine aquaculture zones. AB - The accumulation of toxic inorganic nitrogen is one of the major water quality problems in intensive aquaculture systems, thus the N removal in aquaculture systems is an important issue for the sustainable development of aquaculture. To understand one of the major microbial N removal processes, anaerobic ammonium oxidation (anammox), phylogenetic diversity, and distribution of anammox bacteria in sediments of four different marine aquaculture zones in Hong Kong (HK) were investigated. The 16S rRNA genes analysis indicated that sequences detected from Cheung Sha Wan (CSW) and Sok Kwu Wan (SKW) were closely related to several clusters within the Scalindua genus of anammox bacteria, including a new habitat specific group, while only several sequences related to Scalindua and Kuenenia were detected in Sham Wan (SW) and Yim Tin Tsai East (YTTE). Most of the sequences obtained in SW and YTTE with the same PCR primers showed a low similarity to the known anammox bacteria, forming several novel groups within the Planctomycetes. However, results from the hydrazine oxidoreductase (HZO) encoding gene showed that only sequences from SW were related to the genus of Kuenenia, and sequences from other three sites were closely related to the genus of Scalindua. The community analysis showed that CSW and SKW share similar anammox bacterial community structures while SW and YTTE contain a unique anammox bacterial community. Furthermore, correlations reflect that organic matter is positively correlated with Kuenenia-like anammox bacteria, while the redox potential is significantly correlated with Scalindua-like anammox bacteria in marine aquaculture zones. Our results extend the knowledge of anammox bacteria in marine aquaculture systems and highlight the importance of environmental factors in shaping the community structures of anammox bacteria. PMID- 27368741 TI - Paradoxical performance of tryptophan synthase gene trp1 (+) in transformations of the basidiomycete Coprinopsis cinerea. AB - Several transformation strains of Coprinopsis cinerea carry the defective tryptophan synthase allele trp1-1,1-6 which can be complemented by introduction of the trp1 (+) wild-type gene. Regularly in C. cinerea, single-trp1 (+)-vector transformations yield about half the numbers of clones than cotransformations with a non-trp1 (+)-plasmid done in parallel. The effect is also observed with the orthologous Schizophyllum commune trpB (+) gene shown here to function as a selection marker in C. cinerea. Parts of single-trp1 (+) - or single-trpB (+) vector transformants are apparently lost. This paradoxical phenomenon relates to de-regulation of aromatic amino acid biosynthesis pathways. Adding tryptophan precursors to protoplast regeneration agar or feeding with other aromatic amino acids increases loss of single-trp1 (+)-vector transformants and also sets off loss of clones in cotransformation with a non-trp1 (+)-plasmid. Feedback control by tryptophan and cross-pathway control by tyrosine and phenylalanine are both active in the process. We deduce from the observations that more cotransformants than single-vector transformants are obtained by in average less disturbance of the tryptophan biosynthesis pathway. DNA in C. cinerea transformation usually integrates into the genome at multiple ectopic places. Integration events for a single vector per nucleus should statistically be 2-fold higher in single-vector transformations than in cotransformations in which the two different molecules compete for the same potential integration sites. Integration of more trp1 (+) copies into the genome might more likely lead to sudden tryptophan overproduction with subsequent rigid shut-down of the pathway. Blocking ectopic DNA integration in a Deltaku70 mutant abolished the effect of doubling clone numbers in cotransformations due to preferred single trp1 (+) integration by homologous recombination at its native genomic site. PMID- 27368742 TI - Toxoplasmosis presenting with a subtle maculopapular eruption in a child post hematopoietic stem cell transplantation. PMID- 27368743 TI - Imaging diagnoses and outcome in patients presenting for primary angioplasty but no obstructive coronary artery disease. AB - OBJECTIVE: A proportion of patients with suspected ST-elevation myocardial infarction (STEMI) presenting for primary percutaneous coronary intervention (PPCI) do not have obstructive coronary disease and other conditions may be responsible for their symptoms and ECG changes. In this study, we set out to determine the prevalence and aetiology of alternative diagnoses in a large PPCI cohort as determined with multimodality imaging and their outcome. METHODS: From 2009 to 2012, 5238 patients with suspected STEMI were referred for consideration of PPCI. Patients who underwent angiography but had no culprit artery for revascularisation and no previous history of coronary artery disease were included in the study. Troponin values, imaging findings and all-cause mortality were obtained from hospital and national databases. RESULTS: A total of 575 (13.0%) patients with a mean age of 58+/-15 years (69% men) fulfilled the inclusion criteria. A specific diagnosis based on imaging was made in 237 patients (41.2%) including cardiomyopathies (n=104, 18%), myopericarditis (n=48, 8.4%), myocardial infarction/other coronary abnormality (n=27, 4.9%) and severe valve disease (n=23, 4%). Pulmonary embolism and type A aortic dissection were identified in seven (1.2%) and four (0.7%) cases respectively. A total of 40 (7.0%) patients died over a mean follow-up of 42.6 months. CONCLUSIONS: A variety of cardiac and non-cardiac conditions are prevalent in patients presenting with suspected STEMI but culprit-free angiogram, some of which may have adverse outcomes. Further imaging of such patients could thus be useful to help in appropriate management and follow-up. PMID- 27368744 TI - Comparison of three whole genome amplification methods for detection of genomic aberrations in single cells. AB - OBJECTIVE: Detection of genomic copy number abnormalities in a single cell using array comparative genomic hybridization (CGH) offers a promising non-invasive alternative for prenatal diagnosis. Our objective was to compare three commercially available whole-genome amplification (WGA) kits for their capacity to produce high quality DNA from single cells that is suitable for both molecular genotyping and array CGH. METHODS: We examined kit performance on unfixed, fixed and fixed/permeabilized lymphoblastoid cells. Molecular genotyping methods were used to evaluate the fidelity of amplified DNA for genomic profiling, while array CGH was used to assess copy number from single cells harboring trisomy 21, a DiGeorge syndrome deletion, a CMT1A duplication or a MECP2 duplication. RESULTS: Molecular genotyping was achieved from single cells but performance varied between WGA kits. Furthermore, we consistently detected a dosage difference in sex chromosomes for gender mismatched hybridizations and for chromosome 21 in trisomy 21 cells. The 2.5 Mb DiGeorge syndrome deletion was also detected using all three WGA platforms, whereas the 1.3 Mb CMT1A and the 0.6 Mb MECP2 duplications were not consistently detected. CONCLUSION: These data suggest that single cell molecular genotyping and copy number analysis can be accomplished when WGA conditions are optimized. (c) 2016 John Wiley & Sons, Ltd. PMID- 27368745 TI - Development of novel recombinant biomimetic chimeric MPG-based peptide as nanocarriers for gene delivery: Imitation of a real cargo. AB - In last decades great efforts have been devoted to the study of development of recombinant peptide based vectors that consist of biological motifs with potential applications in gene therapy. Recombinant Biomimetic Chimeric Vectors (rBCVs) are biopolymeric nanocarriers that are designed to mimic viral features to overcome the cellular obstacles in gene transferring pathway into cell nucleus. In this research, we designed and genetically engineered three novel rBCVs with similar sequences that differed in motifs arrangement and motif abundance: MPG-2H1, 2TMPG-2H1 and 2RMPG-2H1. The MPG as a famous amphipathic cell penetrating peptide is the main segment of these constructs which was studied for the first time in association with truncated histone H1 DNA condensing motif. Through the performance of several physicochemical and biological assays, the rBCVs were remarkably examined regarding transfection efficiency. The main objective of this study is focused on the importance of motif design in transfection efficiency of rBCVs on one hand, and the assessment of correlation between structural features and functionality of motifs on the other hand. The results revealed that all three kinds of rBCVs/pDNA nanoparticles with average sizes of 200nm could overwhelm the cellular obstacles associated with gene transfer, and lead to efficient gene delivery. Furthermore, no significant toxicity was perceived and efficient endosome disruptive activity was obtained. It is noteworthy to say among three mentioned constructs 2RMPG-2H1 showed the highest transfection efficiency. Overall the peptide based vectors hold great promise as a nontoxic and effective gene carrier in vitro and in vivo, besides the rational design possibility as the most vital advantages over the other non viral gene delivery vectors. PMID- 27368746 TI - Spheronization mechanism of pharmaceutical material crystals processed by extremely high shearing force using a mechanical powder processor. AB - We aimed to elucidate the mechanism of the spheronization of pharmaceutical material crystals through extremely high shearing force using a mechanical powder processor, which produces spherical crystals without a solvent. The spheronization of theophylline, acetaminophen, clarithromycin, ascorbic acid and lactose was investigated, and the relationship between the spheronization mechanism and material characteristics was also examined. Theophylline and ascorbic acid crystals were partially destroyed during mechanical processing, yielding large particles and dust, and the large fragments were then layered with powder to produce spheres with a core-shell structure. Acetaminophen crystals were completely fragmented under stress, yielding fine particles to which powder then agglomerated to produce spheres with a mosaic structure. Clarithromycin and lactose crystals were not spheronized. Our results showed that the fracture strength of intact material may be closely related to the size of intermediate fragments, determining spheronization mechanism. Furthermore, the results for powder cohesiveness suggest that the materials with moderate-to-high cohesiveness (theophylline, acetaminophen and ascorbic acid) are finally spheronized regardless of the degree of the strength, whereas those with low cohesiveness (clarithromycin and lactose) are not spheronized due to poor granulation. Hence, the cohesiveness of a material has a significant effect on the success of mechanical spheronization processes. PMID- 27368747 TI - Influence of variation in molar ratio on co-amorphous drug-amino acid systems. AB - Molecular interactions were investigated within four different co-amorphous drug amino acid systems, namely indomethacin-tryptophan (Ind-Trp), furosemide tryptophan (Fur-Trp), indomethacin-arginine (Ind-Arg) and furosemide-arginine (Fur-Arg). The co-amorphous systems were prepared by ball milling for 90min at different molar ratios and analyzed by XRPD and DSC. Interactions within the co amorphous samples were evaluated based on the deviation between the actual glass transition temperature (Tg) and the theoretical Tg calculated by the Gordon Taylor equation. The strongest interactions were observed in the 50mol% drug (1:1M ratio) mixtures, with the exception of co-amorphous Ind-Arg where the interactions within the 40mol% drug samples appear equally strong. A particularly large deviation between the theoretical and actual Tgs was observed within co amorphous Ind-Arg and Fur-Arg systems. Further analysis of these co-amorphous systems by (13)C solid-state NMR (ssNMR) and FTIR confirmed that Ind and Fur formed a co-amorphous salt together with Arg. A modified approach of using the Gordon-Taylor equation was applied, using the equimolar co-amorphous mixture as one component, to describe the evolution of the Tgs with varying molar ratio between the drug and the amino acid. The actual Tgs for co-amorphous Ind-Trp, Fur Trp and Fur-Arg were correctly described by this equation, confirming the assumption that the excess component was amorphous forming a homogeneous single component within the co-amorphous mixture without additional interactions. The modified equation described the Tgs of the co-amorphous Ind-Arg with excess Arg less well indicating possible further interactions; however, the FTIR and ssNMR data did not support the presence of additional intermolecular drug-amino acid interactions. PMID- 27368748 TI - Acitretin and aloe-emodin loaded chitin nanogel for the treatment of psoriasis. AB - The present study focuses on the development of an effective topical nanogel formulation of two anti-psoriatic drugs; Acitretin (Act) and Aloe-emodin (AE) using natural polymer chitin. Simple regeneration chemistry was used to prepare Chitin Nanogel Systems (CNGs). The developed control chitin (CNGs) nanogels, acitretin loaded chitin nanogels (ActCNGs) and aloe-emodin loaded chitin nanogels (AECNGs) were characterized by DLS, SEM, FTIR, XRD and TG-DTA. The systems were found to be spherical in shape with a size range of 98+/-10, 138+/-8 and 238+/ 6nm having zeta potential values of +28+/-3, +27+/-3 and +25+/-6mV for CNGs, ActCNGs and AECNGs respectively. The in vitro haemolysis assay revealed that all the nanogel systems are blood compatible. The systems exhibited higher swelling and release at acidic pH. The ex vivo skin permeation studies using porcine skin confirmed the higher deposition of the systems at epidermal and dermal layers, which was confirmed further by fluorescent imaging. The in vivo anti-psoriatic activity study using Perry's mouse tail model and skin safety studies confirmed the potential benefit of the system for topical delivery of acitretin and aloe emodin in psoriasis. PMID- 27368749 TI - Tracking immune-related cell responses to drug delivery microparticles in 3D dense collagen matrix. AB - Beyond the therapeutic purpose, the impact of drug delivery microparticles on the local tissue and inflammatory responses remains to be further elucidated specifically for reactions mediated by the host immune cells. Such immediate and prolonged reactions may adversely influence the release efficacy and intended therapeutic pathway. The lack of suitable in vitro platforms limits our ability to gain insight into the nature of immune responses at a single cell level. In order to establish an in vitro 3D system mimicking the connective host tissue counterpart, we utilized reproducible, compressed, rat-tail collagen polymerized matrices. THP1 cells (human acute monocytic leukaemia cells) differentiated into macrophage-like cells were chosen as cell model and their functionality was retained in the dense rat-tail collagen matrix. Placebo microparticles were later combined in the immune cell seeded system during collagen polymerization and secreted pro-inflammatory factors: TNFalpha and IL-8 were used as immune response readout (ELISA). Our data showed an elevated TNFalpha and IL-8 secretion by macrophage THP1 cells indicating that Placebo microparticles trigger certain immune cell responses under 3D in vivo like conditions. Furthermore, we have shown that the system is sensitive to measure the differences in THP1 macrophage pro-inflammatory responses to Active Pharmaceutical Ingredient (API) microparticles with different API release kinetics. We have successfully developed a tissue-like, advanced, in vitro system enabling selective "readouts" of specific responses of immune-related cells. Such system may provide the basis of an advanced toolbox enabling systemic evaluation and prediction of in vivo microparticle reactions on human immune-related cells. PMID- 27368750 TI - Potential confounding factors in measurement of specific cell-free seminal mRNAs and microRNAs derived from human reproductive organs. AB - Cell-free seminal RNA (cfs-RNA) is mixed transcripts derived from male reproductive organs, and is potential biomarker for the research and diagnosis of male reproductive-related diseases. However, some clinical factors, including age, asymptomatic Ureaplasma urealyticum (UU) infection, scrotal heat stress, abstinence period, and the storage condition of semen samples, may interfere with sperm parameters and the measurement of seminal biomarkers. Accordingly, this study was designed to evaluate the effect of above clinical factors on the measurement of cfs-RNA, aiming to lay a foundation for its research use and potential clinical application. Semen samples were collected according to the selected clinical factors. Cell-free seminal plasma was obtained by centrifugation and total RNA was extracted with TRIzol LS. Selective male reproductive organ-specific cfs-mRNAs and cfs-miRNAs were quantified by quantitative real-time PCR. The concentration and total amount of cfs-mRNAs and cfs-miRNAs in one ejaculate were calculated and compared. ACTB, DDX4 (testis specific), WFDC9 (epididymis-specific), and miR-514a-3p (testis-specific) significantly increased after scrotal heat stress. SEMG1 (seminal vesicle specific) showed declining tendency with the prolonged abstinence period. Age, asymptomatic UU infection, and the storage condition showed no significant impact on the measurement of cfs-RNA. These results indicate that scrotal heat stress significantly interfere with the selected cfs-RNA derived from the testis and epididymis, and abstinence period may affect the yield of cfs-mRNA from seminal vesicle, while other clinical factors has no significant impact on the measurement. Thus, heat exposure and abstinence period should be considered for the cfs-RNA measurement in its research or clinical application. PMID- 27368751 TI - Strenuous physical exercise accelerates the lipid peroxide clearing transport by HDL. AB - PURPOSE: Physical exercise has cardioprotective functions, which have been partly linked to high-density lipoprotein (HDL), and its functions. We studied the effects of endogenous oxidative stress, induced by acute exhaustive physical exercise, on concentration of oxidized HDL lipids. METHODS: Twenty-four male national top-level endurance runners, 12 middle-distance runners and 12 marathon runners performed a maximal run on a treadmill until exhaustion. We analyzed concentrations of oxidized HDL (oxHDLlipids) and LDL lipids (oxLDLlipids), serum antioxidant potential (TRAP), paraoxonase activity and malondialdehyde. Venous blood samples were taken before, immediately, 15 and 90 min after exercise. RESULTS: Immediately after the treadmill run the concentration of oxHDLlipids was increased by 24 % (p < 0.01). Simultaneously, the ratio of oxHDLlipids to oxLDLlipids increased by 55 % and the oxLDLlipids levels decreased by 19 % (p < 0.001), while serum malondialdehyde and TRAP increased by 54 % (p < 0.001) and 29 % (p < 0.01), respectively. After the 90 min recovery the concentration of oxHDLlipids was decreased towards the pre-exercise level, but that of oxLDLlipids remained decreased below pre-exercise values (p < 0.001). The change in oxLDLlipids after the run correlated positively with VO2max (r = 0.67, p < 0.001) and negatively with the change in paraoxonase activity (r = -0.47, p < 0.05). CONCLUSIONS: We conclude that acute exhaustive physical exercise increased the concentration of oxHDLlipids and decreased that of oxLDLlipids and the ratio of oxLDLlipids to oxHDLlipids, which suggests that during physical exercise HDL has an active role in the removal of lipid peroxides. PMID- 27368753 TI - Recent advances in research on magnesium alloys and magnesium-calcium phosphate composites as biodegradable implant materials. AB - Magnesium alloys are modern biocompatible materials suitable for orthopaedic implants due to their biodegradability in biological environment. Many studies indicate that there is a high demand to design magnesium alloys with controllable in vivo corrosion rates and required mechanical properties. A solution to this challenge can be sought in the development of metal matrix composites based on magnesium alloys with addition of relevant alloying elements and bioceramic particles. In this study, the corrosion mechanisms along with corrosion protection methods in magnesium alloys are discussed. The recently developed magnesium alloys for biomedical applications are reviewed. Special attention is given to the newest research results in metal matrix composites composed of magnesium alloy matrix and calcium phosphates, especially hydroxyapatite or tricalcium phosphate, as the second phase with emphasis on the biodegradation behavior, microstructure and mechanical properties in view of potential application of these materials in bone implants. PMID- 27368752 TI - Synthesis and characterization of poly(lactic acid-co-glycolic acid) complex microspheres as drug carriers. AB - Poly(lactic-co-glycolic) acid (PLGA) is synthesized via melt polycondensation directly from lactic acid and glycolic acid with a feed molar ratio of 75/25. Bovine serum albumin, which is used as model protein, is entrapped into the poly(lactic-co-glycolic acid) microspheres with particle size of 260.9 +/- 20.0 nm by the double emulsification method. Then it is the first report of producing more carboxyl groups by poly(lactic-co-glycolic acid) surface hydrolysis. The purpose is developing poly(lactic-co-glycolic acid) microspheres surface, which is modified with chitosan by chemical reaction between carboxyl groups and amine groups. The particle size and the positive zeta potential of the poly(lactic-co glycolic acid)/chitosan microspheres are 388.2 +/- 35.6 nm and 10.4 +/- 2.9 mV, respectively. The drug loading ratio and encapsulation efficacy of poly(lactic-co glycolic acid)/chitosan microspheres are 36.3% and 57.5%, which are higher than PLGA microspheres. Furthermore, the drug burst release of poly(lactic-co-glycolic acid)/chitosan microspheres at 10 h is decreased to 21.72% while the corresponding value of the poly(lactic-co-glycolic acid) microsphere is 64.56%. These results reveal that surface hydrolysis modification of poly(lactic-co glycolic acid) is an efficient method to improve the negative potential and chemical reaction properties of the polymer. And furthermore, this study shows that chitosan-modified poly(lactic-co-glycolic acid) microspheres is a promising system for the controlled release of pharmaceutical proteins. PMID- 27368754 TI - Divisome and segrosome components of Deinococcus radiodurans interact through cell division regulatory proteins. AB - The Deinococcus radiodurans genome encodes many of the known components of divisome as well as four sets of genome partitioning proteins, ParA and ParB on its multipartite genome. Interdependent regulation of cell division and genome segregation is not understood. In vivo interactions of D. radiodurans' sdivisome, segrosome and other cell division regulatory proteins expressed on multicopy plasmids were studied in Escherichia coli using a bacterial two-hybrid system and confirmed by co-immunoprecipitation with the proteins made in E. coli. Many of these showed interactions both with the self and with other proteins. For example, DrFtsA, DrFtsZ, DrMinD, DrMinC, DrDivIVA and all four ParB proteins individually formed at least homodimers, while DrFtsA interacted with DrFtsZ, DrFtsW, DrFtsE, DrFtsK and DrMinD. DrMinD also showed interaction with DrFtsW, DrFtsE and DrMinC. Interestingly, septum site determining protein, DrDivIVA showed interactions with secondary genome ParAs as well as ParB1, ParB3 and ParB4 while DrMinC interacted with ParB1 and ParB3. PprA, a pleiotropic protein recently implicated in cell division regulation, neither interacted with divisome proteins nor ParBs but interacted at different levels with all four ParAs. These results suggest the formation of independent multiprotein complexes of 'DrFts' proteins, segrosome proteins and cell division regulatory proteins, and these complexes could interact with each other through DrMinC and DrDivIVA, and PprA in D. radiodurans. PMID- 27368755 TI - A Comparison of Fourth-Year Health Sciences Students' Knowledge of Gross Lower and Upper Limb Anatomy: A Cross-Sectional Study. AB - OBJECTIVE: The aim of the study was to assess and compare the knowledge of fourth year medicine, physiotherapy (PT), nursing, and podiatry students in carpal and tarsal bone anatomy. METHODS: A cross-sectional study was carried out. Based on a nonprobability convenience sampling, 177 fourth-year students (117 women and 60 men, mean age of 23.16 +/- 3.82 years) from the podiatry (n = 39), nursing (n = 26), PT (n = 73), and medicine (n = 39) schools at a large Spanish university were included. Measurements were taken of their gross anatomy knowledge by means of the carpal and the tarsal bone tests. Students were asked to identify all carpal and tarsal bones in an illustration of the bony skeleton of both regions and were given a maximum of 5 minutes per test. RESULTS: Of a total of 15 bones to be labeled, the PT (11.07 +/- 3.30) and podiatry (9.36 +/- 2.93) students had the highest rate of correct answers compared with the medicine (6.13 +/- 3.27) and nursing (4.04 +/- 3.72) undergraduates. When assessing academic degrees and test scores, significant differences were observed between PT and podiatry participants vs those from the medicine and nursing schools (P < .001). CONCLUSION: Fourth-year students from the PT and podiatry programs correctly identified a higher number of carpal and tarsal bones than students from the nursing and medicine schools. PMID- 27368756 TI - Neck Flexor and Extensor Muscle Endurance in Subclinical Neck Pain: Intrarater Reliability, Standard Error of Measurement, Minimal Detectable Change, and Comparison With Asymptomatic Participants in a University Student Population. AB - OBJECTIVE: The aims of this study were to assess intrarater reliability and to calculate the standard error of measurement (SEM) and minimal detectable change (MDC) for deep neck flexor and neck extensor muscle endurance tests, and compare the results between individuals with and without subclinical neck pain. METHODS: Participants were students of the University of Aveiro reporting subclinical neck pain and asymptomatic participants matched for sex and age to the neck pain group. Data on endurance capacity of the deep neck flexors and neck extensors were collected by a blinded assessor using the deep neck flexor endurance test and the extensor endurance test, respectively. Intraclass correlation coefficients (ICCs), SEM, and MDC were calculated for measurements taken within a session by the same assessor. Differences between groups for endurance capacity were investigated using a Mann-Whitney U test. RESULTS: The deep neck flexor endurance test (ICC = 0.71; SEM = 6.91 seconds; MDC = 19.15 seconds) and neck extensor endurance test (ICC = 0.73; SEM = 9.84 minutes; MDC = 2.34 minutes) are reliable. No significant differences were found between participants with and without neck pain for both tests of muscle endurance (P > .05). CONCLUSION: The endurance capacity of the deep neck flexors and neck extensors can be reliably measured in participants with subclinical neck pain. However, the wide SEM and MDC might limit the sensitivity of these tests. PMID- 27368758 TI - Trends For Smaller Medical Journals. PMID- 27368757 TI - Subjective Mental Workload and Its Correlation With Musculoskeletal Disorders in Bank Staff. AB - OBJECTIVE: The purpose of this study was to evaluate the rate of subjective mental workload (SMWL) and its correlation with musculoskeletal disorders among bank staff members in Kurdistan Province located in western Iran. METHODS: This cross-sectional study was conducted among 200 bank staff members in Kurdistan Province, Iran. The mental workload was assessed using the National Aeronautics and Space Administration-Task Load Index (NASA-TLX) computerized version. NASA TLX is a multidimensional rating procedure that derives an overall workload score based on a weighted average of ratings on 6 subscales. These subscales include Mental Demands, Physical Demands, Temporal Demands, Performance, Effort, Effectiveness, and Frustration. The musculoskeletal disorders (MSDs) were documented with the Nordic Musculoskeletal Questionnaire and generic body diagram. RESULTS: Of the staff members, 78.5% experienced pain at least once during the past year in 1 of their 9 musculoskeletal body regions. The highest frequencies of pain were in the neck and lower back. The NASA-TLX estimated the Effort and Performance scales with mean +/- SD of 72.8 +/- 25.2 and 36 +/- 22.6, respectively, as the maximal and minimal scores among the 6 subscales of SMWL. The statistical analysis of the data revealed that there was a significant correlation between the overall mental workload score and also among the 6 subscales of SMWL separately with MSDs (P < .05). CONCLUSION: SMWL appears to be a risk factor in the incidence of MSDs, so that the odds of MSDs increased by 11% with each additional 1-point increase in SMWL score. PMID- 27368759 TI - Iatrogenic Atrail Septal Defect After Mitral Valve Replacement. AB - The occurrence of an atrial septal defect after insertion of a prosthetic mitral valve is reported. The left atrium was approached through the interatrial septum. The concomitant development of a left ventricular apical aneurysm and of left ventricular dysfunction probably contributed to dehiscence of the septum. PMID- 27368760 TI - Cause D'Erreur Dans La Lecture Des Antibiogrammes : Presence, Non Declaree, D'Un Antiseptique Sur Les Disques. AB - There is a need for legal control of sensitivity discs. False results are obtained by the use of discs containing an antibiotic and an unlabelled antimicrobial drug. Results of sensitivity tests (performed by the disc agar diffusion method) using Levocyclin8 discs furnished by the manufacturers were highly improbable. It appeared that these discs also contained thimerosal with which they were not labelled. Excellent In vitro results were exclusively due to the mercuric compound. This experience clearly illustrates the need for control ensuring that sensitivity discs comply with the manufacturer's description. PMID- 27368761 TI - Selected Summaries. PMID- 27368763 TI - Editorial. PMID- 27368764 TI - The Enhanced Light Absorptance and Device Application of Nanostructured Black Silicon Fabricated by Metal-assisted Chemical Etching. AB - We use metal-assisted chemical etching (MCE) method to fabricate nanostructured black silicon on the surface of C-Si. The Si-PIN photoelectronic detector based on this type of black silicon shows excellent device performance with a responsivity of 0.57 A/W at 1060 nm. Silicon nanocone arrays can be created using MCE treatment. These modified surfaces show higher light absorptance in the near infrared range (800 to 2500 nm) compared to that of C-Si with polished surfaces, and the variations in the absorption spectra of the nanostructured black silicon with different etching processes are obtained. The maximum light absorptance increases significantly up to 95 % in the wavelength range of 400 to 2500 nm. Our recent novel results clearly indicate that nanostructured black silicon made by MCE has potential application in near-infrared photoelectronic detectors. PMID- 27368765 TI - Corrigendum to "Salivary pellicles equalise surfaces' charges and modulate the virulence of Candida albicans biofilm" [Arch. Oral Biol. 66 (2016) 129-140]. PMID- 27368766 TI - Kinks and bell-type solitons in microtubules. AB - In the present paper, we study the nonlinear dynamics of microtubules relying on the known u-model. As a mathematical procedure, we use the simplest equation method. We recover some solutions obtained earlier using less general methods. These are kink solitons. In addition, we show that the solution of the crucial differential equation, describing nonlinear dynamics of microtubules, can be a bell-type soliton. The discovery of this new solution is supported by numerical analysis. PMID- 27368767 TI - Predicting the future trend of popularity by network diffusion. AB - Conventional approaches to predict the future popularity of products are mainly based on extrapolation of their current popularity, which overlooks the hidden microscopic information under the macroscopic trend. Here, we study diffusion processes on consumer-product and citation networks to exploit the hidden microscopic information and connect consumers to their potential purchase, publications to their potential citers to obtain a prediction for future item popularity. By using the data obtained from the largest online retailers including Netflix and Amazon as well as the American Physical Society citation networks, we found that our method outperforms the accurate short-term extrapolation and identifies the potentially popular items long before they become prominent. PMID- 27368768 TI - Synchronization using environmental coupling in mercury beating heart oscillators. AB - We report synchronization of Mercury Beating Heart (MBH) oscillators using the environmental coupling mechanism. This mechanism involves interaction of the oscillators with a common medium/environment such that the oscillators do not interact among themselves. In the present work, we chose a modified MBH system as the common environment. In the absence of coupling, this modified system does not exhibit self sustained oscillations. It was observed that, as a result of the coupling of the MBH oscillators with this common environment, the electrical and the mechanical activities of both the oscillators synchronized simultaneously. Experimental results indicate the emergence of both lag and the complete synchronization in the MBH oscillators. Simulations of the phase oscillators were carried out in order to better understand the experimental observations. PMID- 27368769 TI - Spike-like solitary waves in incompressible boundary layers driven by a travelling wave. AB - Nonlinear waves produced in an incompressible boundary layer driven by a travelling wave are investigated, with damping considered as well. As one of the typical nonlinear waves, the spike-like wave is governed by the driven-damped Benjamin-Ono equation. The wave field enters a completely irregular state beyond a critical time, increasing the amplitude of the driving wave continuously. On the other hand, the number of spikes of solitary waves increases through multiplication of the wave pattern. The wave energy grows in a sequence of sharp steps, and hysteresis loops are found in the system. The wave energy jumps to different levels with multiplication of the wave, which is described by winding number bifurcation of phase trajectories. Also, the phenomenon of multiplication and hysteresis steps is found when varying the speed of driving wave as well. Moreover, the nature of the change of wave pattern and its energy is the stability loss of the wave caused by saddle-node bifurcation. PMID- 27368770 TI - Phase response curves for models of earthquake fault dynamics. AB - We systematically study effects of external perturbations on models describing earthquake fault dynamics. The latter are based on the framework of the Burridge Knopoff spring-block system, including the cases of a simple mono-block fault, as well as the paradigmatic complex faults made up of two identical or distinct blocks. The blocks exhibit relaxation oscillations, which are representative for the stick-slip behavior typical for earthquake dynamics. Our analysis is carried out by determining the phase response curves of first and second order. For a mono-block fault, we consider the impact of a single and two successive pulse perturbations, further demonstrating how the profile of phase response curves depends on the fault parameters. For a homogeneous two-block fault, our focus is on the scenario where each of the blocks is influenced by a single pulse, whereas for heterogeneous faults, we analyze how the response of the system depends on whether the stimulus is applied to the block having a shorter or a longer oscillation period. PMID- 27368771 TI - Controlling chaos-assisted directed transport via quantum resonance. AB - We report on the first demonstration of chaos-assisted directed transport of a quantum particle held in an amplitude-modulated and tilted optical lattice, through a resonance-induced double-mean displacement relating to the true classically chaotic orbits. The transport velocity is controlled by the driving amplitude and the sign of tilt, and also depends on the phase of the initial state. The chaos-assisted transport feature can be verified experimentally by using a source of single atoms to detect the double-mean displacement one by one, and can be extended to different scientific fields. PMID- 27368772 TI - Self-synchronization in an ensemble of nonlinear oscillators. AB - The paper describes the results of study of a system of coupled nonlinear, Duffing-type oscillators, from the viewpoint of their self-synchronization, i.e., generation of a coherent field (order parameter) via instability of an incoherent (random-phase) initial state. We consider both the cases of dissipative coupling (e.g., via the joint radiation) and reactive coupling in a Hamiltonian system. PMID- 27368773 TI - Recovery rate affects the effective epidemic threshold with synchronous updating. AB - Accurate identification of effective epidemic threshold is essential for understanding epidemic dynamics on complex networks. In this paper, we systematically study how the recovery rate affects the susceptible-infected removed spreading dynamics on complex networks, where synchronous and asynchronous updating processes are taken into account. We derive the theoretical effective epidemic threshold and final outbreak size based on the edge-based compartmental theory. To validate the proposed theoretical predictions, extensive numerical experiments are implemented by using asynchronous and synchronous updating methods. When asynchronous updating method is used in simulations, recovery rate does not affect the final state of spreading dynamics. But with synchronous updating, we find that the effective epidemic threshold decreases with recovery rate, and final outbreak size increases with recovery rate. A good agreement between the theoretical predictions and the numerical results are observed on both synthetic and real-world networks. Our results extend the existing theoretical studies and help us to understand the phase transition with arbitrary recovery rate. PMID- 27368774 TI - A novel coefficient for detecting and quantifying asymmetry of California electricity market based on asymmetric detrended cross-correlation analysis. AB - In order to detect and quantify asymmetry of two time series, a novel cross correlation coefficient is proposed based on recent asymmetric detrended cross correlation analysis (A-DXA), which we called A-DXA coefficient. The A-DXA coefficient, as an important extension of DXA coefficient rhoDXA, contains two directional asymmetric cross-correlated indexes, describing upwards and downwards asymmetric cross-correlations, respectively. By using the information of directional covariance function of two time series and directional variance function of each series itself instead of power-law between the covariance function and time scale, the proposed A-DXA coefficient can well detect asymmetry between the two series no matter whether the cross-correlation is significant or not. By means of the proposed A-DXA coefficient conducted over the asymmetry for California electricity market, we found that the asymmetry between the prices and loads is not significant for daily average data in 1999 yr market (before electricity crisis) but extremely significant for those in 2000 yr market (during the crisis). To further uncover the difference of asymmetry between the years 1999 and 2000, a modified H statistic (MH) and DeltaMH statistic are proposed. One of the present contributions is that the high MH values calculated for hourly data exist in majority months in 2000 market. Another important conclusion is that the cross-correlation with downwards dominates over the whole 1999 yr in contrast to the cross-correlation with upwards dominates over the 2000 yr. PMID- 27368775 TI - Prediction uncertainty and optimal experimental design for learning dynamical systems. AB - Dynamical systems are frequently used to model biological systems. When these models are fit to data, it is necessary to ascertain the uncertainty in the model fit. Here, we present prediction deviation, a metric of uncertainty that determines the extent to which observed data have constrained the model's predictions. This is accomplished by solving an optimization problem that searches for a pair of models that each provides a good fit for the observed data, yet has maximally different predictions. We develop a method for estimating a priori the impact that additional experiments would have on the prediction deviation, allowing the experimenter to design a set of experiments that would most reduce uncertainty. We use prediction deviation to assess uncertainty in a model of interferon-alpha inhibition of viral infection, and to select a sequence of experiments that reduces this uncertainty. Finally, we prove a theoretical result which shows that prediction deviation provides bounds on the trajectories of the underlying true model. These results show that prediction deviation is a meaningful metric of uncertainty that can be used for optimal experimental design. PMID- 27368776 TI - Driving-induced multistability in coupled chaotic oscillators: Symmetries and riddled basins. AB - We study the multistability that results when a chaotic response system that has an invariant symmetry is driven by another chaotic oscillator. We observe that there is a transition from a desynchronized state to a situation of multistability. In the case considered, there are three coexisting attractors, two of which are synchronized and one is desynchronized. For large coupling, the asynchronous attractor disappears, leaving the system bistable. We study the basins of attraction of the system in the regime of multistability. The three attractor basins are interwoven in a complex manner, with extensive riddling within a sizeable region of (but not the entire) phase space. A quantitative characterization of the riddling behavior is made via the so-called uncertainty exponent, as well as by evaluating the scaling behavior of tongue-like structures emanating from the synchronization manifold. PMID- 27368777 TI - Noise induced escape from a nonhyperbolic chaotic attractor of a periodically driven nonlinear oscillator. AB - Noise induced escape from the domain of attraction of a nonhyperbolic chaotic attractor in a periodically excited nonlinear oscillator is investigated. The general mechanism of the escape in the weak noise limit is studied in the continuous case, and the fluctuational path is obtained by statistical analysis. Selecting the primary homoclinic tangency as the initial condition, the action plot is presented by parametrizing the set of escape trajectories and the global minimum gives rise to the optimal path. Results of both methods show good agreements. The entire process of escape is discussed in detail step by step using the fluctuational force. A structure of hierarchical heteroclinic crossings of stable and unstable manifolds of saddle cycles is found, and the escape is observed to take place through successive jumps through this deterministic hierarchical structure. PMID- 27368778 TI - Electrostatic and aerodynamic forced vibrations of a thin flexible electrode: Quasi-periodic vs. chaotic oscillations. AB - In this paper, transverse vibrations of an electrostatically actuated thin flexible cantilever perturbed by low-speed air flow are studied using both experiments and numerical modeling. In the experiments, the dynamic characteristics of the cantilever are studied by supplying a DC voltage with an AC component for electrostatic forcing and a constant uniform air flow around the cantilever system for aerodynamic forcing. A range of control parameters leading to stable vibrations are established using a dimensionless operating parameter that is the ratio of the induced and the free stream velocities. Numerical results are validated with experimental data. Assuming the amplitude of vibrations are small, then a non-linear dynamic Euler-Bernoulli beam equation with viscous damping and gravitational effects is used to model the equation of motion. Aerodynamic forcing is modelled as a temporally sinusoidal and uniform force acting perpendicular to the beam length. The forcing amplitude is found to be proportional to the square of the air flow velocity. Numerical results strongly agree with the experiments predicting accurate vibration amplitude, displacement frequency, and quasi-periodic displacement of the cantilever tip. PMID- 27368779 TI - The influence of society's mesoscopic structure on the rate of epidemic spreading. AB - In this study, we investigate the role of the mesoscopic structural properties of a scale-free social network on the contagion spreading. We focus on both the exponent of power-law community size distribution function (beta) and the mixing parameter (MU). Findings show that increasing beta reduces the rate of epidemic spreading. On the other hand, increasing MU increases the rate of epidemic spreading. Two innovating parameters, Temperature and cos theta, are introduced here to analyze these effects. PMID- 27368780 TI - Architecture of chaotic attractors for flows in the absence of any singular point. AB - Some chaotic attractors produced by three-dimensional dynamical systems without any singular point have now been identified, but explaining how they are structured in the state space remains an open question. We here want to explain in the particular case of the Wei system-such a structure, using one-dimensional sets obtained by vanishing two of the three derivatives of the flow. The neighborhoods of these sets are made of points which are characterized by the eigenvalues of a 2 * 2 matrix describing the stability of flow in a subspace transverse to it. We will show that the attractor is spiralling and twisted in the neighborhood of one-dimensional sets where points are characterized by a pair of complex conjugated eigenvalues. We then show that such one-dimensional sets are also useful in explaining the structure of attractors produced by systems with singular points, by considering the case of the Lorenz system. PMID- 27368781 TI - Localized spin excitations in an antiferromagnetic spin system with D-M interaction. AB - The existence of localized spin excitations and spin deviations along the site in a one-dimensional antiferromagnet with Dzyaloshinski-Moriya (D-M) interaction has been studied using quasiclassical approximation. By introducing the Holstein Primakoff bosonic representation of spin operators, the coherent state ansatz, and the time dependent variational principle, a discrete set of coupled nonlinear partial differential equations governing the dynamics is derived. Employing the multiple-scale method, one, two and three solitary wave solutions are constructed and depicted graphically. PMID- 27368782 TI - Multivariate weighted recurrence network inference for uncovering oil-water transitional flow behavior in a vertical pipe. AB - Exploring the dynamical behaviors of high water cut and low velocity oil-water flows remains a contemporary and challenging problem of significant importance. This challenge stimulates us to design a high-speed cycle motivation conductance sensor to capture spatial local flow information. We systematically carry out experiments and acquire the multi-channel measurements from different oil-water flow patterns. Then we develop a novel multivariate weighted recurrence network for uncovering the flow behaviors from multi-channel measurements. In particular, we exploit graph energy and weighted clustering coefficient in combination with multivariate time-frequency analysis to characterize the derived complex networks. The results indicate that the network measures are very sensitive to the flow transitions and allow uncovering local dynamical behaviors associated with water cut and flow velocity. These properties render our method particularly useful for quantitatively characterizing dynamical behaviors governing the transition and evolution of different oil-water flow patterns. PMID- 27368783 TI - Synchronization properties of coupled chaotic neurons: The role of random shared input. AB - Spike-time correlations of neighbouring neurons depend on their intrinsic firing properties as well as on the inputs they share. Studies have shown that periodically firing neurons, when subjected to random shared input, exhibit asynchronicity. Here, we study the effect of random shared input on the synchronization of weakly coupled chaotic neurons. The cases of so-called electrical and chemical coupling are both considered, and we observe a wide range of synchronization behaviour. When subjected to identical shared random input, there is a decrease in the threshold coupling strength needed for chaotic neurons to synchronize in-phase. The system also supports lag-synchronous states, and for these, we find that shared input can cause desynchronization. We carry out a master stability function analysis for a network of such neurons and show agreement with the numerical simulations. The contrasting role of shared random input for complete and lag synchronized neurons is useful in understanding spike time correlations observed in many areas of the brain. PMID- 27368784 TI - Renormalizable two-parameter piecewise isometries. AB - We exhibit two distinct renormalization scenarios for two-parameter piecewise isometries, based on 2pi/5 rotations of a rhombus and parameter-dependent translations. Both scenarios rely on the recently established renormalizability of a one-parameter triangle map, which takes place if and only if the parameter belongs to the algebraic number field K=Q(5) associated with the rotation matrix. With two parameters, features emerge which have no counterpart in the single parameter model. In the first scenario, we show that renormalizability is no longer rigid: whereas one of the two parameters is restricted to K, the second parameter can vary continuously over a real interval without destroying self similarity. The mechanism involves neighbouring atoms which recombine after traversing distinct return paths. We show that this phenomenon also occurs in the simpler context of Rauzy-Veech renormalization of interval exchange transformations, here regarded as parametric piecewise isometries on a real interval. We explore this analogy in some detail. In the second scenario, which involves two-parameter deformations of a three-parameter rhombus map, we exhibit a weak form of rigidity. The phase space splits into several (non-convex) invariant components, on each of which the renormalization still has a free parameter. However, the foliations of the different components are transversal in parameter space; as a result, simultaneous self-similarity of the component maps requires that both of the original parameters belong to the field K. PMID- 27368785 TI - Topic segmentation via community detection in complex networks. AB - Many real systems have been modeled in terms of network concepts, and written texts are a particular example of information networks. In recent years, the use of network methods to analyze language has allowed the discovery of several interesting effects, including the proposition of novel models to explain the emergence of fundamental universal patterns. While syntactical networks, one of the most prevalent networked models of written texts, display both scale-free and small-world properties, such a representation fails in capturing other textual features, such as the organization in topics or subjects. We propose a novel network representation whose main purpose is to capture the semantical relationships of words in a simple way. To do so, we link all words co-occurring in the same semantic context, which is defined in a threefold way. We show that the proposed representations favor the emergence of communities of semantically related words, and this feature may be used to identify relevant topics. The proposed methodology to detect topics was applied to segment selected Wikipedia articles. We found that, in general, our methods outperform traditional bag-of words representations, which suggests that a high-level textual representation may be useful to study the semantical features of texts. PMID- 27368786 TI - Reconstruction of neuronal input through modeling single-neuron dynamics and computations. AB - Mathematical models provide a mathematical description of neuron activity, which can better understand and quantify neural computations and corresponding biophysical mechanisms evoked by stimulus. In this paper, based on the output spike train evoked by the acupuncture mechanical stimulus, we present two different levels of models to describe the input-output system to achieve the reconstruction of neuronal input. The reconstruction process is divided into two steps: First, considering the neuronal spiking event as a Gamma stochastic process. The scale parameter and the shape parameter of Gamma process are, respectively, defined as two spiking characteristics, which are estimated by a state-space method. Then, leaky integrate-and-fire (LIF) model is used to mimic the response system and the estimated spiking characteristics are transformed into two temporal input parameters of LIF model, through two conversion formulas. We test this reconstruction method by three different groups of simulation data. All three groups of estimates reconstruct input parameters with fairly high accuracy. We then use this reconstruction method to estimate the non-measurable acupuncture input parameters. Results show that under three different frequencies of acupuncture stimulus conditions, estimated input parameters have an obvious difference. The higher the frequency of the acupuncture stimulus is, the higher the accuracy of reconstruction is. PMID- 27368787 TI - Pseudorandom number generation using chaotic true orbits of the Bernoulli map. AB - We devise a pseudorandom number generator that exactly computes chaotic true orbits of the Bernoulli map on quadratic algebraic integers. Moreover, we describe a way to select the initial points (seeds) for generating multiple pseudorandom binary sequences. This selection method distributes the initial points almost uniformly (equidistantly) in the unit interval, and latter parts of the generated sequences are guaranteed not to coincide. We also demonstrate through statistical testing that the generated sequences possess good randomness properties. PMID- 27368788 TI - Dynamics of higher-order rational solitons for the nonlocal nonlinear Schrodinger equation with the self-induced parity-time-symmetric potential. AB - The integrable nonlocal nonlinear Schrodinger equation with the self-induced parity-time-symmetric potential [M. J. Ablowitz and Z. H. Musslimani, Phys. Rev. Lett. 110, 064105 (2013)] is investigated, which is an integrable extension of the standard nonlinear Schrodinger equation. Its novel higher-order rational solitons are found using the nonlocal version of the generalized perturbation (1,N-1)-fold Darboux transformation. These rational solitons illustrate abundant wave structures for the distinct choices of parameters (e.g., the strong and weak interactions of bright and dark rational solitons). Moreover, we also explore the dynamical behaviors of these higher-order rational solitons with some small noises on the basis of numerical simulations. PMID- 27368789 TI - Bifurcations of families of 1D-tori in 4D symplectic maps. AB - The regular structures of a generic 4d symplectic map with a mixed phase space are organized by one-parameter families of elliptic 1d-tori. Such families show prominent bends, gaps, and new branches. We explain these features in terms of bifurcations of the families when crossing a resonance. For these bifurcations, no external parameter has to be varied. Instead, the longitudinal frequency, which varies along the family, plays the role of the bifurcation parameter. As an example, we study two coupled standard maps by visualizing the elliptic and hyperbolic 1d-tori in a 3d phase-space slice, local 2d projections, and frequency space. The observed bifurcations are consistent with the analytical predictions previously obtained for quasi-periodically forced oscillators. Moreover, the new families emerging from such a bifurcation form the skeleton of the corresponding resonance channel. PMID- 27368790 TI - Introduction to Focus Issue: Complex Dynamics in Networks, Multilayered Structures and Systems. AB - In the last years, network scientists have directed their interest to the multi layer character of real-world systems, and explicitly considered the structural and dynamical organization of graphs made of diverse layers between its constituents. Most complex systems include multiple subsystems and layers of connectivity and, in many cases, the interdependent components of systems interact through many different channels. Such a new perspective is indeed found to be the adequate representation for a wealth of features exhibited by networked systems in the real world. The contributions presented in this Focus Issue cover, from different points of view, the many achievements and still open questions in the field of multi-layer networks, such as: new frameworks and structures to represent and analyze heterogeneous complex systems, different aspects related to synchronization and centrality of complex networks, interplay between layers, and applications to logistic, biological, social, and technological fields. PMID- 27368791 TI - A biplex approach to PageRank centrality: From classic to multiplex networks. AB - In this paper, we present a new view of the PageRank algorithm inspired by multiplex networks. This new approach allows to introduce a new centrality measure for classic complex networks and a new proposal to extend the usual PageRank algorithm to multiplex networks. We give some analytical relations between these new approaches and the classic PageRank centrality measure, and we illustrate the new parameters presented by computing them on real underground networks. PMID- 27368792 TI - Synchronization unveils the organization of ecological networks with positive and negative interactions. AB - Network science has helped to understand the organization principles of the interactions among the constituents of large complex systems. However, recently, the high resolution of the data sets collected has allowed to capture the different types of interactions coexisting within the same system. A particularly important example is that of systems with positive and negative interactions, a usual feature appearing in social, neural, and ecological systems. The interplay of links of opposite sign presents natural difficulties for generalizing typical concepts and tools applied to unsigned networks and, moreover, poses some questions intrinsic to the signed nature of the network, such as how are negative interactions balanced by positive ones so to allow the coexistence and survival of competitors/foes within the same system? Here, we show that synchronization phenomenon is an ideal benchmark for uncovering such balance and, as a byproduct, to assess which nodes play a critical role in the overall organization of the system. We illustrate our findings with the analysis of synthetic and real ecological networks in which facilitation and competitive interactions coexist. PMID- 27368793 TI - Deep graphs-A general framework to represent and analyze heterogeneous complex systems across scales. AB - Network theory has proven to be a powerful tool in describing and analyzing systems by modelling the relations between their constituent objects. Particularly in recent years, a great progress has been made by augmenting "traditional" network theory in order to account for the multiplex nature of many networks, multiple types of connections between objects, the time-evolution of networks, networks of networks and other intricacies. However, existing network representations still lack crucial features in order to serve as a general data analysis tool. These include, most importantly, an explicit association of information with possibly heterogeneous types of objects and relations, and a conclusive representation of the properties of groups of nodes as well as the interactions between such groups on different scales. In this paper, we introduce a collection of definitions resulting in a framework that, on the one hand, entails and unifies existing network representations (e.g., network of networks and multilayer networks), and on the other hand, generalizes and extends them by incorporating the above features. To implement these features, we first specify the nodes and edges of a finite graph as sets of properties (which are permitted to be arbitrary mathematical objects). Second, the mathematical concept of partition lattices is transferred to the network theory in order to demonstrate how partitioning the node and edge set of a graph into supernodes and superedges allows us to aggregate, compute, and allocate information on and between arbitrary groups of nodes. The derived partition lattice of a graph, which we denote by deep graph, constitutes a concise, yet comprehensive representation that enables the expression and analysis of heterogeneous properties, relations, and interactions on all scales of a complex system in a self-contained manner. Furthermore, to be able to utilize existing network-based methods and models, we derive different representations of multilayer networks from our framework and demonstrate the advantages of our representation. On the basis of the formal framework described here, we provide a rich, fully scalable (and self explanatory) software package that integrates into the PyData ecosystem and offers interfaces to popular network packages, making it a powerful, general purpose data analysis toolkit. We exemplify an application of deep graphs using a real world dataset, comprising 16 years of satellite-derived global precipitation measurements. We deduce a deep graph representation of these measurements in order to track and investigate local formations of spatio-temporal clusters of extreme precipitation events. PMID- 27368794 TI - Inter-layer synchronization in multiplex networks of identical layers. AB - Inter-layer synchronization is a distinctive process of multiplex networks whereby each node in a given layer evolves synchronously with all its replicas in other layers, irrespective of whether or not it is synchronized with the other units of the same layer. We analytically derive the necessary conditions for the existence and stability of such a state, and verify numerically the analytical predictions in several cases where such a state emerges. We further inspect its robustness against a progressive de-multiplexing of the network, and provide experimental evidence by means of multiplexes of nonlinear electronic circuits affected by intrinsic noise and parameter mismatch. PMID- 27368795 TI - Agricultural activity shapes the communication and migration patterns in Senegal. AB - The communication and migration patterns of a country are shaped by its socioeconomic processes. The economy of Senegal is predominantly rural, as agriculture employs over 70% of the labor force. In this paper, we use mobile phone records to explore the impact of agricultural activity on the communication and mobility patterns of the inhabitants of Senegal. We find two peaks of phone calls activity emerging during the growing season. Moreover, during the harvest period, we detect an increase in the migration flows throughout the country. However, religious holidays also shape the mobility patterns of the Senegalese people. Hence, in the light of our results, agricultural activity and religious holidays are the primary drivers of mobility inside the country. PMID- 27368796 TI - Extracting information from multiplex networks. AB - Multiplex networks are generalized network structures that are able to describe networks in which the same set of nodes are connected by links that have different connotations. Multiplex networks are ubiquitous since they describe social, financial, engineering, and biological networks as well. Extending our ability to analyze complex networks to multiplex network structures increases greatly the level of information that is possible to extract from big data. For these reasons, characterizing the centrality of nodes in multiplex networks and finding new ways to solve challenging inference problems defined on multiplex networks are fundamental questions of network science. In this paper, we discuss the relevance of the Multiplex PageRank algorithm for measuring the centrality of nodes in multilayer networks and we characterize the utility of the recently introduced indicator function Theta(S) for describing their mesoscale organization and community structure. As working examples for studying these measures, we consider three multiplex network datasets coming for social science. PMID- 27368797 TI - Intervality and coherence in complex networks. AB - Food webs-networks of predators and prey-have long been known to exhibit "intervality": species can generally be ordered along a single axis in such a way that the prey of any given predator tend to lie on unbroken compact intervals. Although the meaning of this axis-usually identified with a "niche" dimension-has remained a mystery, it is assumed to lie at the basis of the highly non-trivial structure of food webs. With this in mind, most trophic network modelling has for decades been based on assigning species a niche value by hand. However, we argue here that intervality should not be considered the cause but rather a consequence of food-web structure. First, analysing a set of 46 empirical food webs, we find that they also exhibit predator intervality: the predators of any given species are as likely to be contiguous as the prey are, but in a different ordering. Furthermore, this property is not exclusive of trophic networks: several networks of genes, neurons, metabolites, cellular machines, airports, and words are found to be approximately as interval as food webs. We go on to show that a simple model of food-web assembly which does not make use of a niche axis can nevertheless generate significant intervality. Therefore, the niche dimension (in the sense used for food-web modelling) could in fact be the consequence of other, more fundamental structural traits. We conclude that a new approach to food-web modelling is required for a deeper understanding of ecosystem assembly, structure, and function, and propose that certain topological features thought to be specific of food webs are in fact common to many complex networks. PMID- 27368798 TI - Line graphs for a multiplex network. AB - It is well known that line graphs offer a good summary of the graphs properties, which make them easier to analyze and highlight the desired properties. We extend the concept of line graph to multiplex networks in order to analyze multi-plexed and multi-layered networked systems. As these structures are very rich, different approaches to this notion are required to capture a variety of situations. Some relationships between these approaches are established. Finally, by means of some simulations, the potential utility of this concept is illustrated. PMID- 27368799 TI - From neurons to epidemics: How trophic coherence affects spreading processes. AB - Trophic coherence, a measure of the extent to which the nodes of a directed network are organised in levels, has recently been shown to be closely related to many structural and dynamical aspects of complex systems, including graph eigenspectra, the prevalence or absence of feedback cycles, and linear stability. Furthermore, non-trivial trophic structures have been observed in networks of neurons, species, genes, metabolites, cellular signalling, concatenated words, P2P users, and world trade. Here, we consider two simple yet apparently quite different dynamical models-one a susceptible-infected-susceptible epidemic model adapted to include complex contagion and the other an Amari-Hopfield neural network-and show that in both cases the related spreading processes are modulated in similar ways by the trophic coherence of the underlying networks. To do this, we propose a network assembly model which can generate structures with tunable trophic coherence, limiting in either perfectly stratified networks or random graphs. We find that trophic coherence can exert a qualitative change in spreading behaviour, determining whether a pulse of activity will percolate through the entire network or remain confined to a subset of nodes, and whether such activity will quickly die out or endure indefinitely. These results could be important for our understanding of phenomena such as epidemics, rumours, shocks to ecosystems, neuronal avalanches, and many other spreading processes. PMID- 27368800 TI - Cooperative spreading processes in multiplex networks. AB - This study is concerned with the dynamic behaviors of epidemic spreading in multiplex networks. A model composed of two interacting complex networks is proposed to describe cooperative spreading processes, wherein the virus spreading in one layer can penetrate into the other to promote the spreading process. The global epidemic threshold of the model is smaller than the epidemic thresholds of the corresponding isolated networks. Thus, global epidemic onset arises in the interacting networks even though an epidemic onset does not arise in each isolated network. Simulations verify the analysis results and indicate that cooperative spreading processes in multiplex networks enhance the final infection fraction. PMID- 27368801 TI - Optimal distributions for multiplex logistic networks. AB - This paper presents some mathematical models for distribution of goods in logistic networks based on spectral analysis of complex networks. Given a steady distribution of a finished product, some numerical algorithms are presented for computing the weights in a multiplex logistic network that reach the equilibrium dynamics with high convergence rate. As an application, the logistic networks of Germany and Spain are analyzed in terms of their convergence rates. PMID- 27368802 TI - Terminal regions of beta-catenin are critical for regulating its adhesion and transcription functions. AB - beta-Catenin, the central molecule of canonical Wnt signaling pathway, has multiple binding partners and performs many roles in the cell. Apart from being a transcriptional activator, beta-catenin acts as a crucial effector component of cadherin/catenin complex to physically interact with actin cytoskeleton along with alpha-catenin and E-cadherin for regulating cell-cell adhesion. Here, we have generated a library of beta-catenin point and deletion mutants to delineate regions within beta-catenin that are important for alpha-catenin-beta-catenin interaction, nuclear localization, and transcriptional activity of beta-catenin. We observed a unique mechanism for nuclear localization of beta-catenin and its mutants and show that N-terminal exon-3 region and C-terminal domain of beta catenin are critical for this activity of beta-catenin. Furthermore, we show HepG2 cells have high beta-catenin mediated transcriptional activity due to the presence of an interstitial deletion at the N-terminal region of beta-catenin. Due to this deletion mutant (hereupon called TM), GSK3beta and HDAC inhibitors failed to show any impact whereas curcumin significantly inhibited beta-catenin mediated transcriptional activity reiterating that TM is primarily responsible for the high transcriptional activity of HepG2 cells. Moreover, we show the recombinant TM does not physically interact with alpha-catenin, localizes predominantly in the nucleus, and has nearly two-fold higher transcriptional activity than the wildtype beta-catenin. PMID- 27368803 TI - GiniClust: detecting rare cell types from single-cell gene expression data with Gini index. AB - High-throughput single-cell technologies have great potential to discover new cell types; however, it remains challenging to detect rare cell types that are distinct from a large population. We present a novel computational method, called GiniClust, to overcome this challenge. Validation against a benchmark dataset indicates that GiniClust achieves high sensitivity and specificity. Application of GiniClust to public single-cell RNA-seq datasets uncovers previously unrecognized rare cell types, including Zscan4-expressing cells within mouse embryonic stem cells and hemoglobin-expressing cells in the mouse cortex and hippocampus. GiniClust also correctly detects a small number of normal cells that are mixed in a cancer cell population. PMID- 27368804 TI - NFAT5-mediated CACNA1C expression is critical for cardiac electrophysiological development and maturation. AB - Entry of calcium into cardiomyocyte via L-type calcium channel (LTCC) is fundamental to cardiac contraction. CACNA1C, a type of LTCC and a hallmark of a matured ventricular myocyte, is developmentally regulated. Here, we identified 138 potential transcription factors by a comparative genomic study on 5-kb promoter regions of CACNA1C gene across eight vertebrate species, and showed that six factors were developmentally regulated with the expression of Cacna1c in mouse P19cl6 in vitro cardiomyocyte differentiation model. We further demonstrated that the nuclear factor of activated T cells 5 (Nfat5) bound to a consensus sequence TGGAAGCGTTC and activated the transcription of Cacna1c. The siRNA-mediated knockdown of Nfat5 suppressed the expression of Cacna1c and decreased L-type calcium current in mouse neonatal cardiomyocytes. Furthermore, morpholino-mediated knockdown of nfat5 in zebrafish prohibited the expression of cacna1c and resulted in a non-contractile ventricle, while over-expression of either cacna1c or nfat5 rescued this impaired phenotype. Thus, NFAT5-mediated expression of CACNA1C is evolutionarily conserved and critical for cardiac electrophysiological development and maturation of cardiomyocyte. KEY MESSAGE: Nfat5 binds to a consensus sequence TGGAAGCGTTC in the promoter of Cacna1c. Nfat5 activates the transcription of Cacna1c. Nfat5 knockdown suppresses Cacna1c expression, decreases L-type calcium current, and results in non-beating ventricle. NFAT5-mediated expression of CACNA1C is evolutionarily conserved. NFAT5-mediated CACNA1C expression is critical for cardiac electrophysiological development and maturation. PMID- 27368805 TI - Inactivated pepsin inhibits neutrophil activation by Fcgamma-receptor-dependent and independent stimuli. AB - Pepsin is widely used to produce F(ab')2 fragments of immunoglobulin G (IgG). In many cases, at least part of the pepsin will remain present in the F(ab')2 preparation, albeit in (irreversibly) inactivated form. Here we report on a potent immunomodulatory effect of irreversibly inactivated pepsin on activated human neutrophils. Degranulation, induced by coated IgG or via cytochalasin B/N formyl-Met-Leu-Phe, was measured by quantifying elastase release, and was found to be inhibited in a dose-dependent manner by inactivated pepsin. Since a number of intravenous immunoglobulin (IVIg) products are also treated by limited digestion with pepsin, we investigated if pepsin would be present in quantities large enough to inhibit neutrophil activation. The amounts of pepsin detected in three different pepsin-treated IVIg products were found to be too low to induce an effect, at least in an in vitro setting. PMID- 27368806 TI - Slamf6 negatively regulates autoimmunity. AB - The nine SLAM family (Slamf) receptors are positive or negative regulators of adaptive and innate immune responses, and of several autoimmune diseases. Here we report that the transfer of Slamf6-/- B6 CD4+ T cells into co-isogenic bm12 mice causes SLE-like autoimmunity with elevated levels of autoantibodies. In addition, significantly higher percentages of Tfh cells and IFN-gamma-producing CD4+ cells, as well as GC B cells were observed. Interestingly, the expression of the Slamf6 H1 isoform in Slamf6-/- CD4+ T cells did not induce this lupus-like phenotype. By contrast, Slamf1-/- or Slamf5-/- CD4+ T cells caused the same pathology as WT CD4+ T cells. As the transfer of Slamf [1+6]-/- or Slamf [1+5+6]-/- CD4+ T cells induced WT levels of autoantibodies, the presence of Slamf1 was requisite for the induction of increased levels of autoantibodies by Slamf6-/- CD4+ T cells. We conclude that Slamf6 functions as an inhibitory receptor that controls autoimmune responses. PMID- 27368810 TI - [Not Available]. PMID- 27368809 TI - [Not Available]. PMID- 27368808 TI - Review of Mouse Models of Graves' Disease and Orbitopathy-Novel Treatment by Induction of Tolerance. AB - Various approaches have been used to model human Graves' disease in mice, including transfected fibroblasts, and plasmid or adenoviral immunisations with the extracellular A subunit of the human thyrotropin receptor (TSHR). Some of these models were only observed for a short time period or were self-limiting. A long-term model for human Graves' disease was established in mice using continuing immunisations (4-weekly injections) with recombinant adenovirus expressing TSHR. Generation of TSHR binding cAMP-stimulatory antibodies, thyroid enlargement and alterations, elevated serum thyroxin levels, tachycardia and cardiac hypertrophy were maintained for at least 9 months in all Ad-TSHR immunised mice. Here, we show that these mice suffer from orbitopathy, which was detected by serial orbital sectioning and histomorphometry. Attempts to treat established Graves' disease in preclinical mouse model studies have included small molecule allosteric antagonists and specific antagonist antibodies which were isolated from hypothyroid patients. In addition, novel peptides have been conceived which mimic the cylindrical loops of the TSHR leucine-rich repeat domain, in order to re-establish tolerance toward the antigen. Here, we show preliminary results that one set of these peptides improves or even cures all signs and symptoms of Graves' disease in mice after six consecutive monthly injections. First beneficial effects were observed 3-4 months after starting these therapies. In immunologically naive mice, administration of the peptides did not induce any immune response. PMID- 27368811 TI - [Not Available]. PMID- 27368812 TI - [Not Available]. PMID- 27368807 TI - Next-Generation Autoantibody Testing by Combination of Screening and Confirmation the CytoBead(r) Technology. AB - Occurrence of autoantibodies (autoAbs) is a hallmark of autoimmune diseases, and the analysis thereof is an essential part in the diagnosis of organ-specific autoimmune and systemic autoimmune rheumatic diseases (SARD), especially connective tissue diseases (CTDs). Due to the appearance of autoAb profiles in SARD patients and the complexity of the corresponding serological diagnosis, different diagnostic strategies have been suggested for appropriate autoAb testing. Thus, evolving assay techniques and the continuous discovery of novel autoantigens have greatly influenced the development of these strategies. Antinuclear antibody (ANA) analysis by indirect immunofluorescence (IIF) on tissue and later cellular substrates was one of the first tests introduced into clinical routine and is still an indispensable tool for CTD serology. Thus, screening for ANA by IIF is recommended to be followed by confirmatory testing of positive findings employing different assay techniques. Given the continuous growth in the demand for autoAb testing, IIF has been challenged as the standard method for ANA and other autoAb analyses due to lacking automation, standardization, modern data management, and human bias in IIF pattern interpretation. To address these limitations of autoAb testing, the CytoBead(r) technique has been introduced recently which enables automated interpretation of cell-based IIF and quantitative autoAb multiplexing by addressable microbead immunoassays in one reaction environment. Thus, autoAb screening and confirmatory testing can be combined for the first time. The present review discusses the history of autoAb assay techniques in this context and gives an overview and outlook of the recent progress in emerging technologies. PMID- 27368813 TI - [Not Available]. PMID- 27368814 TI - [Not Available]. PMID- 27368815 TI - [Not Available]. PMID- 27368816 TI - [Not Available]. PMID- 27368818 TI - [Not Available]. PMID- 27368817 TI - [Not Available]. PMID- 27368819 TI - [Not Available]. PMID- 27368820 TI - [Not Available]. PMID- 27368821 TI - [Not Available]. PMID- 27368822 TI - [Not Available]. PMID- 27368823 TI - [Not Available]. PMID- 27368824 TI - [Not Available]. PMID- 27368825 TI - [Not Available]. PMID- 27368826 TI - [Not Available]. PMID- 27368827 TI - [Not Available]. PMID- 27368828 TI - [Not Available]. PMID- 27368829 TI - [Not Available]. PMID- 27368831 TI - [Not Available]. PMID- 27368830 TI - Implementation of a patient decision aid for men with localized prostate cancer: evaluation of patient outcomes and practice variation. AB - BACKGROUND: Men with localized prostate cancer often have unrealistic expectations. Practitioners are poor judges of men's preferences, contributing to preference misdiagnosis and unwarranted practice variation. Patient decision aids (PtDAs) can support men with decisions about localized prostate cancer. This is a comparative case study of two strategies for implementing PtDAs in clinical pathways for men with localized prostate cancer, evaluating (a) PtDA use; (b) impact on men, practitioners, and health system outcomes; and (c) factors influencing sustained use. METHODS/DESIGN: Guided by the Knowledge to Action Framework, this comparative case study will be conducted using administrative data, interviews, and surveys. Cases will be bound by geographic location (one hospital in Ontario; province of Saskatchewan) and time. Eligible participants will be all men newly diagnosed with localized prostate cancer, with outcomes assessed using administrative data and interviews. Nurses, urologists, radiation oncologists, and managers will be surveyed and a smaller sample interviewed. Cases will be established for each setting with findings compared across cases. Changes in the proportions of men given the PtDA over 2 years will be determined from administrative data. Factors associated with receiving the PtDA will be explored using multivariable logistic regression analysis. To assess the impact of the PtDA, outcomes will be described using mean and standard deviation (men's decisional conflict) and frequency and proportions (practitioners consulted, uptake of treatment). To estimate the effect of the PtDA on these outcomes, adjusted mean differences and odds ratios will be calculated using exploratory multivariable general linear regression and binary or multinomial logistic regression. Factors influencing sustained PtDA use will be assessed using descriptive analysis of survey findings and thematic analysis of interview transcripts. DISCUSSION: Determining how to embed PtDAs effectively within clinical pathways for men with localized prostate cancer is essential. PtDAs have the potential to strengthen men's active role in making prostate cancer decisions, enhance uptake of shared decision-making by practitioners, and reduce practice variation. Our team of researchers and knowledge users will use findings to improve current PtDA use and consider scaling-up implementation. PMID- 27368833 TI - [Not Available]. PMID- 27368832 TI - [Not Available]. PMID- 27368834 TI - [Not Available]. PMID- 27368836 TI - [Not Available]. PMID- 27368835 TI - [Not Available]. PMID- 27368837 TI - [Not Available]. PMID- 27368838 TI - [Not Available]. PMID- 27368839 TI - [Not Available]. PMID- 27368841 TI - [Not Available]. PMID- 27368840 TI - [Not Available]. PMID- 27368842 TI - [Not Available]. PMID- 27368843 TI - [Not Available]. PMID- 27368844 TI - [Not Available]. PMID- 27368845 TI - [Not Available]. PMID- 27368847 TI - [Not Available]. PMID- 27368846 TI - [Not Available]. PMID- 27368848 TI - [Not Available]. PMID- 27368849 TI - [Not Available]. PMID- 27368850 TI - [Not Available]. PMID- 27368852 TI - [Not Available]. PMID- 27368851 TI - [Not Available]. PMID- 27368853 TI - [Not Available]. PMID- 27368854 TI - [Not Available]. PMID- 27368856 TI - [Not Available]. PMID- 27368855 TI - [Not Available]. PMID- 27368857 TI - [Not Available]. PMID- 27368858 TI - [Not Available]. PMID- 27368859 TI - [Not Available]. PMID- 27368860 TI - [Not Available]. PMID- 27368861 TI - [Not Available]. PMID- 27368862 TI - [Not Available]. PMID- 27368863 TI - [Not Available]. PMID- 27368864 TI - [Not Available]. PMID- 27368865 TI - [Not Available]. PMID- 27368866 TI - [Not Available]. PMID- 27368867 TI - [Not Available]. PMID- 27368868 TI - [Not Available]. PMID- 27368869 TI - [Not Available]. PMID- 27368870 TI - [Not Available]. PMID- 27368871 TI - [Not Available]. PMID- 27368872 TI - [Not Available]. PMID- 27368873 TI - [Not Available]. PMID- 27368875 TI - [Not Available]. PMID- 27368874 TI - [Not Available]. PMID- 27368876 TI - [Not Available]. PMID- 27368877 TI - Slug Is Associated With Tumor Metastasis and Angiogenesis in Ovarian Cancer. AB - Ovarian cancer is the most lethal gynecologic malignancy among women and usually initiated by the malignant transformation of epithelial cells. The progression of ovarian cancer involves a cascade of events, including tumor cell epithelial mesenchymal transition (EMT), invasion, migration, and angiogenesis. Slug plays vital roles in the development of motile and invasive manner of cancer cells via EMT progression. The present work is devoted to investigate the effect of slug on the invasion and angiogenesis in ovarian cancer. The findings reveal that tumors with high expression of slug (44 of 60) represent higher tumor grade, lymph node metastasis, and worse prognosis than those with low expression (16 of 60; P < .05). We also identified a significant correlation between the slug and the microvessel density (MVD). Results of transwell migration assay showed that decreased slug induced by short hairpin RNA contributed to the repressed invasion and migration of SKOV3 cells. Additionally, the migration and tube formation capacity of human umbilical vein endothelial cells were markedly decreased in SKOV3-sh-conditioned medium compared to SKOV3 and SKOV3-NC. Furthermore, xenograft mouse models (SKOV3/SKOV3-sh cells injection into BALB/c nude mice) were developed to validate the effects of slug. The data confirmed that inhibited expression of slug extensively decreased the growth of tumor and MVD in vivo. Moreover, knockdown of slug can significantly reduce tumor angiogenesis of SKOV3 cells via ccn1/vascular endothelial growth factor. Thus, our present study demonstrates that slug is closely associated with tumor metastasis and angiogenesis in ovarian cancer. PMID- 27368879 TI - Obstetrics and Gynecology Residency and Fertility Needs. AB - Infertility is a common reproductive disease, with a prevalence of 9% to 18% of the general population. To date, no studies have attempted to examine the prevalence and experience of infertility among resident physicians in the United States. In female obstetrics and gynecology (Ob/Gyn) residents of age where infertility becomes more prevalent, ability to seek fertility may be influenced by rigorous professional demands and low remuneration. We seek to understand the prevalence of infertility, as well as experience and utilization of infertility services among Ob/Gyn residents. Cross-sectional descriptive survey was distributed among US Accreditation Council for Graduate Medical Education accredited Ob/Gyn programs. Demographics, intentions to conceive during residency, fertility problems, fertility treatment, affordability of care, and perceptions of support were surveyed. A total of 241 responses were received in an equal distribution between junior (n = 120) and senior (n = 121) residents. The majority of respondents were female (91%), 25 to 35 years old (94%), and married (54%). Eighty-five percent (195 of 230) did not actively pursue fertility during residency. Twenty-nine percent (68 of 235) considered fertility preservation, but only 2% sought consultation. Twenty-nine percent of those interested in fertility (22 of 75) experienced infertility of some degree. Sixty three percent felt low or no support from the program. Thirty-five percent reported stigma associated with their infertility. In conclusion, infertility is a prevalent reproductive health impairment among Ob/Gyn residents. The majority of residents defer childbearing during residency despite advancing reproductive age. A majority felt little or no support from training programs in addressing their fertility care. Further studies are indicated to understand the barriers and impact among resident trainees. PMID- 27368880 TI - Follow-up in non-muscle-invasive bladder cancer-International Bladder Cancer Network recommendations. AB - OBJECTIVE: Non-muscle-invasive bladder cancer (NMIBC) comprises a wide spectrum of tumors with different behaviors and prognoses. It follows that the surveillance for these tumors should be adapted according to the risks of recurrence and progression and should be dynamic in design. METHODS AND MATERIALS: Medline search was conducted from 1980 to 2016 using a combination of MeSH and keyword terms. The highest available evidence was reviewed to define different risk groups in NMIBC. The performance of different follow-up tools such as urine cytology, cystoscopy, and upper tract imaging in detecting bladder carcinoma was assessed. Different commercially available urinary markers were investigated to determine whether such markers would contribute to the surveillance of patients with NMIBC. A follow-up scheme based on the early evidence is proposed. RESULTS: A risk-based approach is paramount. Cystoscopy and cytology are recommended to be done at 3 months following transurethral resection of bladder tumor. For low-risk tumors, annual cystoscopy alone is sufficient; no upper tract evaluations or cytology is needed except at diagnosis. High-risk tumors should be followed up with a more intense schedule: cystoscopy every 3 months for 2 years, 6 months for 2 years, and then annually, with cytology at frequent intervals, and imaging for upper tract evaluation at 1 year and then every 2 years. Intermediate-risk tumors should be subclassified as per the International Bladder Cancer Group recommendations and when associated with 3 or more of the following findings (multiple tumors, size>=3cm, early recurrence<1 year, frequent recurrences>1 per year) then a surveillance strategy similar to that of high risk should be followed. Several urine markers were more sensitive than cytology in the detection of NMIBC; however, these tests are still costly, require specialized laboratories, and do not replace cystoscopy. Until better and cheaper markers are available, their routine use has not been integrated in the follow-up recommendation of current guidelines. CONCLUSIONS: Surveillance of NMIBC should follow a risk-adapted approach, with a combination of cystoscopy, cytology, and upper tract imaging. The aim of this approach is to minimize the therapeutic burden of a disease with high recurrence rates without missing progressing tumors. When designing a diagnostic pathway, first-line diagnostic imaging tests should have high sensitivity to ensure disease positives are included in the test population for further investigation. Second-line investigations should be highly specific, to ensure false-positives are minimized. PMID- 27368881 TI - Palbociclib in Combination With Fulvestrant in Women With Hormone Receptor Positive/HER2-Negative Advanced Metastatic Breast Cancer: Detailed Safety Analysis From a Multicenter, Randomized, Placebo-Controlled, Phase III Study (PALOMA-3). AB - BACKGROUND: Palbociclib enhances endocrine therapy and improves clinical outcomes in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer (MBC). Because this is a new target, it is clinically important to understand palbociclib's safety profile to effectively manage toxicity and optimize clinical benefit. MATERIALS AND METHODS: Patients with endocrine-resistant, HR-positive/HER2-negative MBC (n = 521) were randomly assigned 2:1 to receive fulvestrant (500 mg intramuscular injection) with or without goserelin with oral palbociclib (125 mg daily; 3 weeks on/1 week off) or placebo. Safety assessments at baseline and day 1 of each cycle included blood counts on day 15 for the first 2 cycles. Hematologic toxicity was assessed by using laboratory data. RESULTS: A total of 517 patients were treated (palbociclib, n = 345; placebo, n = 172); median follow-up was 8.9 months. With palbociclib, neutropenia was the most common grade 3 (55%) and 4 (10%) adverse event; median times to onset and duration of grade >=3 episodes were 16 and 7 days, respectively. Asian ethnicity and below-median neutrophil counts at baseline were significantly associated with an increased chance of developing grade 3-4 neutropenia with palbociclib. Dose modifications for grade 3-4 neutropenia had no adverse effect on progression-free survival. In the palbociclib arm, febrile neutropenia occurred in 3 (<1%) patients. The percentage of grade 1-2 infections was higher than in the placebo arm. Grade 1 stomatitis occurred in 8% of patients. CONCLUSION: Palbociclib plus fulvestrant treatment was well-tolerated, and the primary toxicity of asymptomatic neutropenia was effectively managed by dose modification without apparent loss of efficacy. This study appears at ClinicalTrials.gov, NCT01942135. IMPLICATIONS FOR PRACTICE: Treatment with palbociclib in combination with fulvestrant was generally safe and well-tolerated in patients with hormone receptor (HR)-positive metastatic breast cancer. Consistent with the drug's proposed mechanism of action, palbociclib related neutropenia differs in its clinical time course, patterns, and consequences from those seen with chemotherapy. Neutropenia can be effectively managed by a dose reduction, interruption, or cycle delay without compromising efficacy. A significant efficacy gain and a favorable safety profile support the consideration of incorporating palbociclib into the routine management of HR positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. PMID- 27368878 TI - Research Priorities for Endometriosis. AB - The 3rd International Consensus Workshop on Research Priorities in Endometriosis was held in Sao Paulo on May 4, 2014, following the 12th World Congress on Endometriosis. The workshop was attended by 60 participants from 19 countries and was divided into 5 main sessions covering pathogenesis/pathophysiology, symptoms, diagnosis/classification/prognosis, disease/symptom management, and research policy. This research priorities consensus statement builds on earlier efforts to develop research directions for endometriosis. Of the 56 research recommendations from the 2011 meeting in Montpellier, a total of 41 remained unchanged, 13 were updated, and 2 were deemed to be completed. Fifty-three new research recommendations were made at the 2014 meeting in Sao Paulo, which in addition to the 13 updated recommendations resulted in a total of 66 new recommendations for research. The research recommendations published herein, as well as those from the 2 previous papers from international consensus workshops, are an attempt to promote high-quality research in endometriosis by identifying and agreeing on key issues that require investigation. New areas included in the 2014 recommendations include infertility, patient stratification, and research in emerging nations, in addition to an increased focus on translational research. A revised and updated set of research priorities that builds on this document will be developed at the 13th World Congress on Endometriosis to be held on May 17-20, 2017, in Vancouver, British Columbia, Canada. PMID- 27368884 TI - [Not Available]. PMID- 27368882 TI - Physical Functioning in Older Patients With Breast Cancer: A Prospective Cohort Study in the TEAM Trial. AB - BACKGROUND: Previous retrospective studies have shown that physical functioning in older cancer survivors is affected after treatment, yet prospective data are lacking. The aim of this study was to assess change in physical functioning in different age groups of patients with hormone receptor-positive breast cancer who were enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) phase III trial. METHODS: Two physical parameters were assessed. Physical functioning was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire 1 year (T1) and 2 years (T2) after diagnosis. Physical activity was measured in metabolic equivalent of task (MET) hours/week at T1 and T2. Physical activity before diagnosis (T0) was assessed retrospectively at the T1 questionnaire. Patients were divided into three age groups: <60, 60-69, and >=70 years. Decline in physical functioning was assessed using linear regression analysis. Differences in mean values of physical activity levels were calculated using repeated-measures one-way analysis of variance. RESULTS: A total of 431 patients were included for analysis. In all age groups, physical activity levels at T1 and T2 were significantly lower than prediagnostic physical activity levels (T0) (p < .001 for all age groups). Age >=70 years was independently associated with decline in physical functioning between T1 and T2 (beta = -4.62, 95% confidence interval -8.73 to -0.51, p = .028). CONCLUSION: Patients aged 70 years or older treated with breast surgery and adjuvant hormonal therapy did not improve between years 1 and 2 after diagnosis to the same extent as did younger patients. IMPLICATIONS FOR PRACTICE: Although older patients constitute a large share of the breast cancer population, little is known about the effect and consequences of treatment of breast cancer in this specific age group. This study revealed that, unlike younger patients, older patients do not regain their physical abilities after surgical and adjuvant treatment for breast cancer. In older adults, the effect of treatment on physical functioning and independency could be more relevant than survival outcomes. Clinicians and older patients should be aware of the impact of treatment on physical functioning and prevent older patients from experiencing physical decline, which could lead to institutionalization and loss of independence. There is a need for age-specific guidelines that take into account the heterogeneity of the older population and for evidence-based treatment that focuses not only on cancer-specific outcomes but also on the consequences of treatment for physical and cognitive functioning and quality of life. PMID- 27368885 TI - [Not Available]. PMID- 27368886 TI - [Not Available]. PMID- 27368883 TI - An Introduction to a Head and Neck Cancer-Specific Frailty Index and Its Clinical Implications in Elderly Patients: A Prospective Observational Study Focusing on Respiratory and Swallowing Functions. AB - INTRODUCTION: Frailty refers to a decreased physiologic reserve in geriatric patients and its importance in terms of treatment planning and outcome prediction has been emphasized in oncologic practices for older patients with cancer. We investigated the clinical implications of a head and neck cancer (HNC)-specific frailty index suggested by prospective clinical and functional evaluations of HNC patients. MATERIALS AND METHODS: We analyzed data on 165 elderly patients with HNC who were prospectively enrolled in our hospital from 2010 to 2013. Pretreatment functional evaluations were performed according to all comprehensive geriatric assessment (CGA) domains. We additionally evaluated the patients' respiratory and swallowing functions using pulmonary function tests, voice handicap index (VHI), MD Anderson Dysphagia Inventory (MDADI), and other associated tests. Factors affecting the 2-year morbidity and mortality were also analyzed. RESULTS: Respiratory and swallowing problems were major causes of 2 year morbidity. Pretreatment performance status, VHI >=8, MDADI <70, dental problems, and chemotherapy were significantly associated with early morbidity and mortality (all p < .05). CGA-assessed frailty was found in 72 patients (43.6%) and was significantly associated with 2-year mortality (p = .027) but not with morbidity (p = .716). The high-risk group according to our new HNC-specific frailty index that included functional evaluations of respiration and swallowing showed significantly higher 2-year morbidity (p = .043) and mortality (p < .001). CONCLUSION: Pretreatment functional disabilities related to respiration and swallowing were significantly associated with early morbidity and mortality. The suggested index would be more useful for assessing frailty in elderly HNC patients. IMPLICATIONS FOR PRACTICE: This study is the first report in terms of suggesting a new frailty index focusing on respiratory and swallowing functions in elderly patients with head and neck cancer. This study shows that functional disabilities associated with respiration and swallowing significantly affected early morbidity and mortality in these elderly patients. The head and neck cancer specific frailty index described in this report, which includes functional evaluations of respiration and swallowing, significantly predicted both early morbidity and mortality. PMID- 27368887 TI - [Not Available]. PMID- 27368888 TI - [Not Available]. PMID- 27368889 TI - [Not Available]. PMID- 27368890 TI - [Not Available]. PMID- 27368891 TI - [Not Available]. PMID- 27368892 TI - [Not Available]. PMID- 27368893 TI - [Not Available]. PMID- 27368895 TI - [Not Available]. PMID- 27368894 TI - [Not Available]. PMID- 27368896 TI - [Not Available]. PMID- 27368897 TI - [Not Available]. PMID- 27368899 TI - [Not Available]. PMID- 27368898 TI - [Not Available]. PMID- 27368900 TI - [Not Available]. PMID- 27368902 TI - [Not Available]. PMID- 27368901 TI - [Not Available]. PMID- 27368903 TI - [Not Available]. PMID- 27368904 TI - [Not Available]. PMID- 27368905 TI - [Not Available]. PMID- 27368906 TI - [Not Available]. PMID- 27368908 TI - [Not Available]. PMID- 27368907 TI - [Not Available]. PMID- 27368909 TI - [Not Available]. PMID- 27368910 TI - [Not Available]. PMID- 27368911 TI - [Not Available]. PMID- 27368912 TI - [Not Available]. PMID- 27368913 TI - A Novel Mutation in IKBKG/NEMO Leads to Ectodermal Dysplasia with Severe Immunodeficiency (EDA-ID). PMID- 27368914 TI - The relationship between the violet pigment PP-V production and intracellular ammonium level in Penicillium purpurogenum. AB - Penicillium purpurogenum is the fungus that produces an azaphilone pigment. However, details about the pigment biosynthesis pathway are unknown. The violet pigment PP-V is the one of the main pigments biosynthesized by this fungus. This pigment contains an amino group in a pyran ring as its core structure. We focused on this pigment and examined the relationship between intracellular ammonium concentration and pigment production using glutamine as a nitrogen source. The intracellular ammonium level decreased about 1.5-fold in conditions favoring PP-V production. Moreover, P. purpurogenum was transferred to medium in which it commonly produces the related pigment PP-O after cultivating it in the presence or absence of glutamine to investigate whether this fungus biosynthesizes PP-V using surplus ammonium in cells. Only mycelia cultured in medium containing 10 mM glutamine produced the violet pigment, and simultaneously intracellular ammonium levels decreased under this condition. From comparisons of the amount of PP-V that was secreted with quantity of surplus intracellular ammonium, it is suggested that P. purpurogenum maintains ammonium homeostasis by excreting waste ammonium as PP-V. PMID- 27368915 TI - Comparison of dosimetric parameters and acute toxicity of intensity-modulated and three-dimensional radiotherapy in patients with cervix carcinoma: A randomized prospective study. AB - PURPOSE: The use of intensity-modulated radiotherapy (IMRT) to treat cervix carcinoma has increased, however prospective randomized trials are still lacking. AIM: To compare the dosimetric parameters and associated acute toxicity in patients with cervix carcinoma treated with three-dimensional (3D) conformal radiotherapy and IMRT. PATIENTS AND METHODS: Forty patients were randomized in two arms each consisting of 20 patients. Patients in both arms received concurrent chemoradiation (cisplatin 40mg/m(2) weekly; 50Gy/25 fractions). Patients were treated with 3D conformal radiotherapy in one arm and with IMRT in another arm. After external beam radiotherapy, all patients received brachytherapy (21Gy/3 fractions at weekly interval). For dosimetric comparison, both kinds of the plans were done for all the patients. All patients were assessed throughout and until 90 days after completion of treatment for acute gastrointestinal, genitourinary and hematologic toxicities. RESULTS: Both plans achieved adequate planning target volume coverage, while mean conformity index was found significantly better in IMRT plans (P-value=0.001). D35 (dose to 35% volume) and D50 for bladder was reduced by 14.62 and 32.57% and for rectum by 23.82 and 43.68% in IMRT. For IMRT, V45 (volume receiving 45Gy) of bowel were found significantly lesser (P-value=0.0001), non-tumour integral dose was found significantly higher (P-value=0.0240) and V20 of bone marrow was found significantly reduced (P-value=0.019) in comparison to that in 3D conformal radiotherapy. Significant reduction of grade 2 or more (20 vs 45%; P-value=0.058) and grade>=3 (5 vs 15%, P-value=0.004) acute genitourinary toxicity and grade 2 or more (20 vs 45%, P-value=0.003) and grade 3 or more (5 vs. 20%, P-value=0.004) acute gastrointestinal toxicity while no significant difference for grade 2 and 3 or more haematological toxicity was noted in patients treated with IMRT compared to 3D conformal radiotherapy. CONCLUSION: IMRT provide a good alternative for treatment of cervix carcinoma with lower acute gastrointestinal and acute genitourinary toxicity with similar target coverage compared to 3D conformal radiotherapy. PMID- 27368916 TI - Improved extracellular expression and high-cell-density fed-batch fermentation of chitosanase from Aspergillus Fumigatus in Escherichia coli. AB - Chitosanase (CSN) from Aspergillus fumigatus has good thermal stability, wide pH range duration, and effective hydrolysis for chitosan. Inhere, CSN was successfully expressed in Escherichia coli followed by extracellular secretion under the guidance of an N-terminal signal peptide PelB, which effectively prompted its secretion out of E. coli cells. To facilitate its later purification, N-terminal or C-terminal 6xHis epitope tag was added to the PelB CSN protein complex. Our results indicated that PelB-CSN without 6xHis-tag (PelB CSN) or with N-terminal 6xHis-tag (PelB-CSN-N) can both be effectively secreted into the medium, while CSN with 6xHis-tag anchored at C-terminus was expressed as inclusion bodies. Process optimization strategies were further developed to improve the secretion efficiency of recombinant PelB-CSN-N in E. coli. Under the induction of 10 g/L lactose in shake-flask culture, the extracellular activity of CSN reached 6015 U/mL at 25 degrees C in TB medium containing 1 % glycine. Moreover, a fed-batch fermentation strategy for high-cell-density cultivation was applied in a 5-L fermenter, increasing the extracellular CSN activity to 14,000 U/mL in 2-day fermentation with the optimal addition of lactose and glycine. PMID- 27368917 TI - Response to letter from Chudleigh et al.: Systematic reviews of hand hygiene in patient care post 2010. PMID- 27368919 TI - Response to Comment on 'epic3: revised recommendation for intravenous catheter and catheter site care'. PMID- 27368918 TI - Comment on 'epic3: revised recommendation for intravenous catheter and catheter site care'. PMID- 27368920 TI - Interpreting the Joint Working Party Guidelines for cleaning up after carbapenemase-producing organisms: the devil's in the dilution. PMID- 27368921 TI - Lipid Nanocarrier: an Efficient Approach Towards Ocular Delivery of Hydrophilic Drug (Valacyclovir). AB - This research focuses on the fabrication and evaluation of solid lipid nanoparticles (SLNs) for improved ocular delivery of valacyclovir (VAC). Stearic acid and tristearin were selected as the lipid carrier while Poloxamer 188 and sodium taurocholate were used as surfactant and co-surfactant, respectively. The physiochemical properties of the optimized batch (SLN-6) fulfil the prerequisites needed for an ideal ocular formulation like submicron size (202.5 +/- 2.56 nm), narrow PDI (0.252 +/- 0.06), high zeta potential (-34.4 +/- 3.04 mV) and good entrapment efficiency (58.82 +/- 2.45%). The in vitro release study of SLN-6 exhibited a sustained release profile (>60% in 12 h). The ex vivo studies performed on excised cornea exhibited enhanced drug permeation of SLNs (22.17 +/- 1.41 MUg/cm2 h) in comparison to the drug solution (3.78 +/- 1.34 MUg/cm2 h). Apart, the corneal hydration studies, histopathology and Hen's Egg Test Chorio Allantoic Membrane (HETCAM) assay, confirmed the non-irritancy of SLNs. The in vivo study confirmed improved ocular bioavailability of VAC from SLN-6 (AUC0-12: 856.47 +/- 7.86 MUg h/mL) in contrast to the drug solution (AUC0-12: 470.75 +/- 8.91 MUg h/mL). Hence, the overall studies suggested the potential of SLNs in efficient ocular delivery of a hydrophilic molecule like VAC. PMID- 27368922 TI - Quercetin-Loaded Solid Lipid Nanoparticle Dispersion with Improved Physicochemical Properties and Cellular Uptake. AB - The objective of this study was to formulate and characterize properties of solid lipid nanoparticle (SLN) dispersion containing quercetin. SLN was prepared by ultrasonication method using tripalmitin and lecithin as lipid core and then the surface was coated with chitosan. Entrapment efficiency was greater than 99%, and mean particle size of SLN was 110.7 +/- 1.97 nm with significant increase in the coated SLN (c-SLN). Zeta potential was proportionally increased and reached plateau at 5% of chitosan coating with respect to tripalmitin. Differential scanning calorimetry showed disappearance of endothermic peak of quercetin in SLNs, indicating conversion of crystalline state to amorphous state. FTIR study of SLNs showed no change in the spectrum of quercetin, which indicates that the lipid and chitosan were not incompatible with quercetin. When coating amount was greater than 2.5% of tripalmitin, particle size and zeta potential were very stable even at 40 degrees C up to 90 days. All SLN dispersions showed significantly faster release profile compared to pure quercetin powder. At pH 7.0, the release rate was increased in proportion to the coating amount. Interestingly, at pH 3.0, chitosan coating of 5.0% or greater decreased the rate. Cellular uptake of quercetin was performed using Caco-2 cells and showed that all SLN dispersions were significantly better than quercetin dispersed in distilled water. However, cellular uptake of quercetin from c-SLN was significantly lower than that from uncoated SLN. PMID- 27368923 TI - Insulin, insulin receptors, and cancer. AB - Insulin is a major regulator of cell metabolism but, in addition, is also a growth factor. Insulin effects in target cells are mediated by the insulin receptor (IR), a transmembrane protein with enzymatic (tyrosine kinase) activity. The insulin receptor, however, is represented by a heterogeneous family of proteins, including two different IR isoforms and also hybrid receptors resulting from the IR hemireceptor combination with a hemireceptor of the cognate IGF-1 receptor. These different receptors may bind insulin and its analogs with different affinity and produce different biologic effects. Since many years, it is known that many cancer cells require insulin for optimal in vitro growth. Recent data indicate that: (1) insulin stimulates growth mainly via its own receptor and not the IGF-1 receptor; (2) in many cancer cells, the IR is overexpressed and the A isoform, which has a predominant mitogenic effect, is more represented than the B isoform. These characteristics provide a selective growth advantage to malignant cells when exposed to insulin. For this reason, all conditions of hyperinsulinemia, both endogenous (prediabetes, metabolic syndrome, obesity, type 2 diabetes before pancreas exhaustion and polycystic ovary syndrome) and exogenous (type 1 diabetes) will increase the risk of cancer. Cancer-related mortality is also increased in patients exposed to hyperinsulinemia but other factors, related to the different diseases, may also contribute. The complexity of the diseases associated with hyperinsulinemia and their therapies does not allow a precise evaluation of the cancer-promoting effect of hyperinsulinemia, but its detrimental effect on cancer incidence and mortality is well documented. PMID- 27368924 TI - Arterio-portal shunts in the cirrhotic liver: perfusion computed tomography for distinction of arterialized pseudolesions from hepatocellular carcinoma. AB - OBJECTIVES: To determine perfusion computed tomography (P-CT) findings for distinction of arterial pseudolesions (APL) from hepatocellular carcinoma (HCC) in the cirrhotic liver. METHODS: 32 APL and 21 HCC in 20 cirrhotic patients (15 men; 65 +/- 10 years), who underwent P-CT for evaluation of HCC pre- (N = 9) or post- (N = 11) transarterial chemoembolization, were retrospectively included using CT follow-up as the standard of reference. All 53 lesions were qualitatively (visual) and quantitatively (perfusion parameters) analysed according to their shape (wedge, irregular, nodular), location (not-/adjunct to a fistula), arterial liver perfusion (ALP), portal venous liver perfusion (PLP), hepatic perfusion index (HPI). Accuracy for diagnosis of HCC was determined using receiver operating characteristics. RESULTS: 18/32 (56 %) APL were wedge shaped, 10/32 (31 %) irregular and 4/32 (12 %) nodular, while 11/21 (52 %) HCC were nodular or 10/21 (48 %) irregular, but never wedge shaped. Significant difference between APL and HCC was seen for lesion shape in pretreated lesions (P < 0.001), and for PLP and HPI in both pre- and post-treated lesions (all, P < 0.001). Diagnostic accuracy for HCC was best for combined assessment of lesion configuration and PLP showing an area under the curve of 0.901. CONCLUSION: Combined assessment of lesion configuration and portal venous perfusion derived from P-CT allows best to discriminate APL from HCC with high diagnostic accuracy. KEY POINTS: * Arterio-portal shunting is common in the cirrhotic liver, especially after local treatment. * Arterial pseudolesions (APL) due to shunting might mimic hepatocellular carcinoma (HCC). * Perfusion-CT allows for qualitative and quantitative assessment of liver lesions. * Lesion configuration fails to discriminate APL from HCC in locally treated patients. * Integration of quantitative perfusion analysis improves accuracy for diagnosis of HCC. PMID- 27368926 TI - Dissimilatory nitrate reduction to ammonium conserves nitrogen in anthropogenically affected subtropical mangrove sediments in Southeast China. AB - In this study, basic sediment properties, nutrient flux, and nitrogen cycle (including denitrification, anaerobic ammonium oxidation [anammox], nitrification, and dissimilatory nitrate reduction to ammonium [DNRA]) were investigated at two sampling sites with different tree ages in the mangrove region of the Jiulong River Estuary, China. The results show that sediments at mangrove flat area have relatively strong capability to reduce NO3(-), in which the DNRA rate is relatively high (204.53+/-48.32MUmolNm(-2)h(-1)), which is approximately 75.7-85.9% of the total NO3(-) reduction, while the denitrification and anammox rates are relatively low - only approximately 5.6-9.5% and 8.5-14.8% of the total NO3(-) reduction, respectively. Thus, in the nitrogen-enriched subtropical mangrove system, DNRA is the main pathway to reduce NO3(-), and most of the input nitrogen is conserved as NH4(+) in the system, which assures high productivity of the mangrove system. PMID- 27368925 TI - Hypertensive heart disease versus hypertrophic cardiomyopathy: multi-parametric cardiovascular magnetic resonance discriminators when end-diastolic wall thickness >= 15 mm. AB - OBJECTIVES: European guidelines state left ventricular (LV) end-diastolic wall thickness (EDWT) >=15mm suggests hypertrophic cardiomyopathy (HCM), but distinguishing from hypertensive heart disease (HHD) is challenging. We identify cardiovascular magnetic resonance (CMR) predictors of HHD over HCM when EDWT >=15mm. METHODS: 2481 consecutive clinical CMRs between 2014 and 2015 were reviewed. 464 segments from 29 HCM subjects with EDWT >=15mm but without other cardiac abnormality, hypertension or renal impairment were analyzed. 432 segments from 27 HHD subjects with EDWT >=15mm but without concomitant cardiac pathology were analyzed. Magnitude and location of maximal EDWT, presence of late gadolinium enhancement (LGE), LV asymmetry (>1.5-fold opposing segment) and systolic anterior motion of the mitral valve (SAM) were measured. Multivariate logistic regression was performed. Significance was defined as p<0.05. RESULTS: HHD and HCM cohorts were age-/gender-matched. HHD had significantly increased indexed LV mass (110+/-27g/m2 vs. 91+/-31g/m2, p=0.016) but no difference in site or magnitude of maximal EDWT. Mid-wall LGE was significantly more prevalent in HCM. Elevated indexed LVM, mid-wall LGE and absence of SAM were significant multivariate predictors of HHD, but LV asymmetry was not. CONCLUSIONS: Increased indexed LV mass, absence of mid-wall LGE and absence of SAM are better CMR discriminators of HHD from HCM than EDWT >=15mm. KEY POINTS: * Hypertrophic cardiomyopathy (HCM) is often diagnosed with end-diastolic wall thickness >=15mm. * Hypertensive heart disease (HHD) can be difficult to distinguish from HCM. * Retrospective case-control study showed that location and magnitude of EDWT are poor discriminators. * Increased left ventricular mass and midwall fibrosis are independent predictors of HHD. * Cardiovascular magnetic resonance parameters facilitate a better discrimination between HHD and HCM. PMID- 27368927 TI - Virtual increase or latent loss? A reassessment of mangrove populations and their conservation in Guangdong, southern China. AB - Contrary to the global trend, the area of mangrove in Guangdong Province, southern China, has been increasing over the last two decades. Currently, three exotic mangrove species have been introduced for large-scale afforestation since 1985. A reassessment of the overall status of the mangrove species, habitat change, population of introduced species, was conducted through a comprehensive literature review as well as field investigations covering 96 sites. The success of conservation efforts is also evaluated. Upstream and high intertidal habitats are more vulnerable than downstream and lower intertidal ones, with habitat alteration being the biggest threats. Five mangrove species have narrow distributional extents with small populations, which could incur regional extinction. With the introduced species having naturalized at 42 sites, their role in mangrove management needs to be reconsidered. These findings collectively suggest a need to manage latent species loss and habitat degradation beyond the apparent increase in mangrove area and protection. PMID- 27368928 TI - Assessing the bio-mitigation effect of integrated multi-trophic aquaculture on marine environment by a numerical approach. AB - With increasing concern over the aquatic environment in marine culture, the integrated multi-trophic aquaculture (IMTA) has received extensive attention in recent years. A three-dimensional numerical ocean model is developed to explore the negative impacts of aquaculture wastes and assess the bio-mitigation effect of IMTA systems on marine environments. Numerical results showed that the concentration of surface phytoplankton could be controlled by planting seaweed (a maximum reduction of 30%), and the percentage change in the improvement of bottom dissolved oxygen concentration increased to 35% at maximum due to the ingestion of organic wastes by sea cucumbers. Numerical simulations indicate that seaweeds need to be harvested in a timely manner for maximal absorption of nutrients, and the initial stocking density of sea cucumbers >3.9 individuals m(-2) is preferred to further eliminate the organic wastes sinking down to the sea bottom. PMID- 27368929 TI - Primary adrenal leiomyosarcoma with lymph node metastasis: a case report. AB - BACKGROUND: Leiomyosarcomas typically originate in smooth muscle cell. Leiomyosarcoma potentially arising from the adrenal gland is an extremely rare mesenchymal tumors associated with delayed diagnosis and poor prognosis. CASE PRESENTATION: A 34-year-old man visited our department complaining of right hypochondriac pain. Computed tomography demonstrated a solid mass measuring 5.2 cm in diameter above the right kidney, corresponding to the right adrenal gland, and a lymph node mass, which appeared to have invaded the IVC wall. Right adrenalectomy and lymphadenectomy were performed. A microscopic examination revealed primary adrenal leiomyosarcoma with lymph node metastasis. No adjuvant therapy was performed, and the patient remains recurrence-free at 10 months postoperatively. CONCLUSIONS: We experienced a very rare case of primary adrenal leiomyosarcoma. Aggressive surgical resection including vascular reconstruction may be associated with improved survival. PMID- 27368932 TI - [Not Available]. PMID- 27368930 TI - Targeted stimulation of retinoic acid receptor-gamma mitigates the formation of heterotopic ossification in an established blast-related traumatic injury model. AB - Heterotopic ossification (HO) involves formation of endochondral bone at non skeletal sites, is prevalent in severely wounded service members, and causes significant complications and delayed rehabilitation. As common prophylactic treatments such as anti-inflammatory drugs and irradiation cannot be used after multi-system combat trauma, there is an urgent need for new remedies. Previously, we showed that the retinoic acid receptor gamma agonist Palovarotene inhibited subcutaneous and intramuscular HO in mice, but those models do not mimic complex combat injury. Thus, we tested Palovarotene in our validated rat trauma-induced HO model that involves blast-related limb injury, femoral fracture, quadriceps crush injury, amputation and infection with methicillin-resistant Staphylococcus aureus from combat wound infections. Palovarotene was given orally for 14days at 1mg/kg/day starting on post-operative day (POD) 1 or POD-5, and HO amount, wound dehiscence and related processes were monitored for up to 84days post injury. Compared to vehicle-control animals, Palovarotene significantly decreased HO by 50 to 60% regardless of when the treatment started and if infection was present. Histological analyses showed that Palovarotene reduced ectopic chondrogenesis, osteogenesis and angiogenesis forming at the injury site over time, while fibrotic tissue was often present in place of ectopic bone. Custom gene array data verified that while expression of key chondrogenic and osteogenic genes was decreased within soft tissues of residual limb in Palovarotene-treated rats, expression of cartilage catabolic genes was increased, including matrix metalloproteinase-9. Importantly, Palovarotene seemed to exert moderate inhibitory effects on wound healing, raising potential safety concerns related to dosing and timing. Our data show for the first time that Palovarotene significantly inhibits HO triggered by blast injury and associated complications, strongly indicating that it may prevent HO in patients at high risk such as those sustaining combat injuries and other forms of blast trauma. PMID- 27368933 TI - [Not Available]. PMID- 27368934 TI - [Not Available]. PMID- 27368931 TI - Use of a Pediatric Cardiovascular Nursing Consortium for Development and Evaluation of Quality Measures: The C4-MNP Experience. AB - The evidence linking nursing care and patient outcomes has been globally demonstrated. Thus, it is time for translation and application of this evidence to robust measurement that uniquely demonstrates the value of nursing care and the characteristics of the nursing workforce that contribute to optimal patient outcomes. OBJECTIVE: The aim of this study was to identify and develop standardized measures representative of pediatric nursing care of the cardiovascular patient for benchmarking within freestanding children's hospitals. METHODS: Using a consensus-based approach, the Consortium of Congenital Cardiac Care- Measurement of Nursing Practice (C4-MNP) members developed quality measures within working groups and then individually critiqued all drafted measures. Final draft measures were then independently reviewed and critiqued by an external nursing quality measurement committee. The final quality measures were also made available to a national parent support group for feedback. OUTCOMES: The development process used by C4-MNP resulted in 10 measures eligible for testing across freestanding children's hospitals. Employing a collaborative consensus based method plus implementing the criteria of the National Quality Forum and external vetting period provided a strong framework for the development and evaluation of standardized measures. NEXT STEPS: The Consortium will continue with implementation and testing of each measure in 9 of our 28 collaborating centers. This activity will support initial development of benchmarks and evaluation of the association of the measures with patient outcomes. PMID- 27368936 TI - [Not Available]. PMID- 27368935 TI - [Not Available]. PMID- 27368937 TI - [Not Available]. PMID- 27368938 TI - [Not Available]. PMID- 27368939 TI - [Not Available]. PMID- 27368940 TI - [Not Available]. PMID- 27368941 TI - [Not Available]. PMID- 27368942 TI - [Not Available]. PMID- 27368943 TI - [Not Available]. PMID- 27368944 TI - [Not Available]. PMID- 27368945 TI - [Not Available]. PMID- 27368947 TI - [Not Available]. PMID- 27368946 TI - [Not Available]. PMID- 27368948 TI - [Not Available]. PMID- 27368950 TI - [Not Available]. PMID- 27368949 TI - [Not Available]. PMID- 27368951 TI - [Not Available]. PMID- 27368952 TI - [Not Available]. PMID- 27368954 TI - [Not Available]. PMID- 27368953 TI - [Not Available]. PMID- 27368956 TI - [Not Available]. PMID- 27368955 TI - Fundus autofluorescence as a marker of disease severity in Vogt-Koyanagi-Harada disease. PMID- 27368957 TI - [Not Available]. PMID- 27368958 TI - [Not Available]. PMID- 27368959 TI - [Not Available]. PMID- 27368960 TI - [Not Available]. PMID- 27368961 TI - [Not Available]. PMID- 27368962 TI - The onset risk of carcinoma in patients continuing tacrolimus topical treatment for oral lichen planus: a case report. AB - Oral lichen planus is a chronic inflammatory mucocutaneous disease. Topical use of steroids and other immuno-modulating therapies have been tried for this intractable condition. Nowadays, tacrolimus ointment is used more commonly as a choice for treatment. However, a number of discussions have taken place after tacrolimus was reported to be carcinogenic. This report describes a patient who applied tacrolimus ointment to the lower lip after being diagnosed with oral lichen planus in 2008, and whose lesion developed squamous cell carcinoma in 2010. Since the relationship between tacrolimus and cancer development has been reported in only a few cases, including this case report, the clinician must be careful selecting tacrolimus as a second-line treatment for oral lichen planus. PMID- 27368968 TI - Adults at risk. AB - An online Safeguarding Adults at Risk information hub has been set up in Northern Ireland by the Department of Health, Social Services and Public Safety, as a resource for practitioners, managers, researchers, educators and policy makers. PMID- 27368969 TI - Older people initiative. AB - Interlinks is a Europe-wide project to create a resource aimed at improving long term care for older people. The project has developed. PMID- 27368963 TI - Inhibitory effect of alpha-mangostin on Candida biofilms. AB - The objective of this study was to determine the inhibitory effect of alpha mangostin on Candida biofilms. Candida species including Candida albicans, Candida krusei, Candida tropicalis, and Candida glabrata were tested. Candida biofilms were formed in flat-bottomed 96-well microtiter plates. The metabolic activity of cells within biofilms was quantified using the XTT assay. The results demonstrated that alpha-mangostin showed a significant anti-biofilm effect on both developing biofilms and preformed biofilms of Candida species. It may be concluded that alpha-mangostin could be an anti-biofilm agent against Candida species. Further in vivo investigations are needed to uncover the therapeutic values of this medicinal plant. PMID- 27368970 TI - Safe care advice. AB - An NHS website dedicated to helping organisations achieve the aims of an initiative to deliver 'harm-free care' by December 2012 contains a wealth of information, tools and resources. Harm-free care is defined as the absence of pressure ulcers, falls, urinary tract infections and venous thromboembolism. PMID- 27368971 TI - Industrial disputes guidance. AB - In response to requests from employers, NHS Employers has developed guidance for managing industrial disputes in the NHS. PMID- 27368973 TI - Out for consultation. AB - More than one million patient safety incidents are reported to the National Patient Safety Agency's national reporting and learning system every year. PMID- 27368974 TI - Erratum to: JAK3-STAT pathway blocking benefits in experimental lupus nephritis. PMID- 27368977 TI - [Not Available]. PMID- 27368975 TI - Expanding the molecular diversity and phenotypic spectrum of glycerol 3-phosphate dehydrogenase 1 deficiency. AB - Transient infantile hypertriglyceridemia (HTGT1; OMIM #614480) is a rare autosomal recessive disorder, which manifests in early infancy with transient hypertriglyceridemia, hepatomegaly, elevated liver enzymes, persistent fatty liver and hepatic fibrosis. This rare clinical entity is caused by inactivating mutations in the GPD1 gene, which encodes the cytosolic isoform of glycerol-3 phosphate dehydrogenase. Here we report on four patients from three unrelated families of diverse ethnic origins, who presented with hepatomegaly, liver steatosis, hypertriglyceridemia, with or without fasting ketotic hypoglycemia. Whole exome sequencing revealed the affected individuals to harbor deleterious biallelic mutations in the GPD1 gene, including the previously undescribed c.806G > A (p.Arg269Gln) and c.640T > C (p.Cys214Arg) mutations. The clinical features in three of our patients showed several differences compared to the original reports. One subject presented with recurrent episodes of fasting hypoglycemia along with hepatomegaly, hypetriglyceridemia, and elevated liver enzymes; the second showed a severe liver disease, with intrahepatic cholestasis associated with kidney involvement; finally, the third presented persistent hypertriglyceridemia at the age of 30 years. These findings expand the current knowledge of this rare disorder, both with regard to the phenotype and molecular basis. The enlarged phenotypic spectrum of glycerol-3-phosphate dehydrogenase 1 deficiency can mimic other inborn errors of metabolism with liver involvement and should alert clinicians to recognize this entity by considering GPD1 mutations in appropriate clinical settings. PMID- 27368976 TI - Membrane progesterone receptors in reproduction and cancer. AB - Progesterone is a sexual steroid hormone that has a critical role in reproductive processes in males and females of several species, including humans. Furthermore, progesterone has been associated with pathological diseases such as breast, gynecological and brain cancer, regulating cell proliferation, apoptosis, and metastasis. In the past, progesterone actions were thought to be only mediated by its intracellular receptor (PR). However, recent evidence has demonstrated that membrane progesterone receptors (mPRs) mediate most of the non-classical progesterone actions. The role of the different mPRs subtypes in progesterone effects in reproduction and cancer is an emerging and exciting research area. Here we review studies to date regarding mPRs role in reproduction and cancer and discuss their functions and clinical relevance, suggesting mPRs as putative pharmacological targets and disease markers in cancer and diseases associated with reproduction. PMID- 27368978 TI - [Not Available]. PMID- 27368979 TI - [Not Available]. PMID- 27368980 TI - [Not Available]. PMID- 27368981 TI - [Not Available]. PMID- 27368982 TI - [Not Available]. PMID- 27368984 TI - [Not Available]. PMID- 27368983 TI - [Not Available]. PMID- 27368985 TI - [Not Available]. PMID- 27368986 TI - [Not Available]. PMID- 27368987 TI - Boronic acid disk diffusion for the phenotypic detection of polymerase chain reaction-confirmed, carbapenem-resistant, gram-negative bacilli isolates. AB - BACKGROUND: The Middle East is regarded as a secondary reservoir for OXA-48 and New Delhi metallo-beta-lactamase (NDM) carbapenemases. One of the main challenges in clinical microbiology diagnostics is the detection of carbapenemases. For this reason simple screening methods have been sought to detect carbapenemase producers to determine appropriate therapeutic measures and implement infection control interventions. The present study aimed to evaluate the efficacy of the modified Hodge test (MHT) and a boronic acid-based combined disk test using carbapenems as substrates for the phenotypic determination of OXA-48 and NDM type carbapenemases in 45 epidemiologically unrelated carbapenem-resistant clinical isolates of Klebsiella pneumoniae (13 isolates), Acinetobacter baumanii (20 isolates), and Pseudomonas aeruginosa (12 isolates). RESULTS: Boronic acid disk test using meropenem as substrate and 600 ug of 3- aminophenylboronic acid (APB) was the most sensitive method (83.33 %) for detection of OXA-48, while the most specific method was MHT (100 %). As regards NDM carbapenemase, boronic acid disk tests using imipenem and 600 ug of APB per disk, and meropenem with 300 or 600 ug of APB were the most sensitive methods (87.50 %), while the most specific method was the MHT (100 %). CONCLUSIONS: The results of the present study indicate that phenotypic screening with the MHT and the boronic acid disk test may be used to detect OXA-48 and NDM carbapenemases in Gram-negative bacilli clinical isolates, and that these tests can be easily applied in tertiary care settings with minimal infrastructure. PMID- 27368988 TI - Maternity care and Human Rights: what do women think? AB - BACKGROUND: A human rights approach to maternal health is considered as a useful framework in international efforts to reduce maternal mortality. Although fundamental human rights principles are incorporated into legal and medical frameworks, human rights have to be translated into measurable actions and outcomes. So far, their substantive applications remain unclear. The aim of this study is to explore women's perspectives and experiences of maternal health services through a human rights perspective in Magu District, Tanzania. METHODS: This study is a qualitative exploration of perspectives and experiences of women regarding maternity services in government health facilities. The point of departure is a Human Rights perspective. A total of 36 semi-structured interviews were held with 17 women, between the age of 31 and 63, supplemented with one focus group discussion of a selection of the interviewed women, in three rural villages and the town centre in Magu District. Data analysis was performed using a coding scheme based on four human rights principles: dignity, autonomy, equality and safety. RESULTS: Women's experiences of maternal health services reflect several sub-standard care factors relating to violations of multiple human rights principles. Women were aware that substandard care was present and described a range of ways how the services could be delivered that would venerate human rights principles. Prominent themes included: 'being treated well and equal', 'being respected' and 'being given the appropriate information and medical treatment'. CONCLUSION: Women in this rural Tanzanian setting are aware that their experiences of maternity care reflect violations of their basic rights and are able to voice what basic human rights principles mean to them as well as their desired applications in maternal health service provision. PMID- 27368989 TI - Analysis of pulmonary non-tuberculous mycobacterial infections after lung transplantation. AB - PURPOSE: Non-tuberculous mycobacteria (NTM) are important pathogens in lung transplant recipients. This study describes the spectrum of NTM respiratory tract infections and examines the association of NTM infections with lung transplant complications. METHODS: Data from 208 recipients transplanted from November 1990 to November 2005 were analyzed. Follow-up data were available to November 2010. Lung infection was defined by bronchoalveolar lavage, sputum, or blood cultures in the appropriate clinical setting. All identified NTM respiratory tract infections were tabulated. The cohort of patients with NTM lung infections (NTM+) were compared to the cohort without infection (NTM-). Univariate and multivariate analysis was performed to determine characteristics associated with NTM infection. Survival analyses for overall survival and development of bronchiolitis obliterans syndrome (BOS) were also performed. RESULTS: In total, 52 isolates of NTM lung infection were identified in 30 patients. The isolates included Mycobacterium abscessus (46%), Mycobacterium avium complex (MAC) (36%), Mycobacterium gordonae (9%), Mycobacterium chelonae (7%), and Mycobacterium fortuitum (2%), with multiple NTM isolates seen on 3 different occasions. The overall incidence was 14%, whereas cumulative incidences at 1, 3, and 5 years after lung transplantation were 11%, 15%, and 20%, respectively. Comparisons between the NTM+ and NTM- cohorts revealed that NTM+ patients were more likely to be African-American and have cytomegalovirus mismatch. Although no difference was seen in survival, the NTM+ cohort was more likely to develop BOS (80% vs. 58%, P = 0.02). NTM+ infection, however, was not independently associated with development of BOS by multivariate analysis. CONCLUSION: With nearly 20 years of follow-up, 14% of lung recipients develop NTM respiratory tract infections, with M. abscessus and MAC more commonly identified. M. gordonae was considered responsible for nearly 10% of NTM infections. Although survival of patients with NTM infections is similar, a striking difference in BOS rates is present in the NTM+ and NTM- groups. PMID- 27368990 TI - Antiretroviral drug resistance mutations in naive and experienced patients in Shiraz, Iran, 2014. AB - Resistance to antiretroviral agents is a significant concern in the clinical management of HIV-infected individuals, particularly in areas of the world where treatment options are limited. In this study, we aimed to identify HIV drug resistance-associated mutations in 40 drug-naive patients and 62 patients under antiretroviral therapy (ART) referred to the Shiraz HIV/AIDS Research Center - the first such data available for the south of Iran. HIV reverse transcriptase and protease genes were amplified and sequenced to determine subtypes and antiretroviral- resistance-associated mutations (RAMs). Subtype CRF35-AD recombinant was the most prevalent in all patients (98 of 102, 96 %), followed by subtype A1, and subtype B (one each, 2 %). Among the 40 ART-naive patients, two mutations associated with nucleoside reverse transcriptase inhibitor (NRTI) resistance (two with Y115F and T215I) and three associated with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance (two with G190S and Y181C, four with V179T) were found. Among ART-experienced patients, four mutations associated with resistance to NRTI, four with NNRTI, and five with protease inhibitors (PI) were found. Twenty patients with high levels of resistance were already on second-line therapy. We document for the first time in this region of Iran high levels of ART resistance to multiple drugs. Our findings call for more vigilant systematic ART resistance surveillance, increased resistance testing, careful management of patients with existing regimens, and strong advocacy for expansion of available drugs in Iran. PMID- 27368991 TI - Complete genome sequence of tobacco mosqueado virus. AB - We describe the genomic characteristics of a new potyvirus isolated from tobacco plants showing mottling ("mosqueado" in Portuguese) in southern Brazil. The complete genomic sequence consists of 9896 nucleotides, without the poly(A) tail, and shares the highest pairwise nucleotide sequence identities of 68.5 % with pepper yellow mosaic virus and 68.2 % with Brugmansia mosaic virus isolate D437. These identity values are below the level of 76.0 % used as a criterion for species demarcation in the genus Potyvirus based on the complete genome sequence. The viral genomic organization and sequence comparison thus suggest that this virus, tentatively named "tobacco mosqueado virus" (TMosqV), represents a new potyvirus species. PMID- 27368993 TI - Complete genome sequences of a putative new alphapartitivirus detected in Rosa spp. AB - A putative new alphapartitivirus was detected by next-generation sequencing (NGS) in Rosa spp. and identified as rose partitivirus isolate Phyllis Bide (RoPV-PB). The virus is bipartite with a dsRNA1 fragment (1937 bp) encoding a putative RdRp and a dsRNA2 fragment (1811 bp) encoding the putative CP subunit of the virus. dsRNA1 of RoPV-BP is closely related to Vicia faba partitivirus 1, with identities of 67 % and 72 % for the nucleotide (nt) and deduced amino acid (aa) sequences, respectively. In NGS analysis of RoPV-BP, coverage was uneven across both dsRNA fragments, with GC/AT content appearing to be a major determinant of depth of coverage. PMID- 27368992 TI - Impact of oseltamivir use on the reduction of complications in patients with influenza: a prospective study. AB - To evaluate the factors associated with oseltamivir prescription and to study the effectiveness of oseltamivir in reducing influenza-related complications. A prospective cohort study using the SOS Doctors (a network of physicians who perform house-call visits in Attica, Greece). Patients with confirmed or clinically suspected influenza were followed up to 14 days during the 2011-2012 influenza period. 410 patients with confirmed or suspected influenza were included. Healthy adults were mainly enrolled, with a median age of 44 years. Influenza diagnosis was mainly based on clinical criteria (65.8 % of patients). Oseltamivir was prescribed for 45.4 % of them. In a multivariate analysis, prescription of oseltamivir was associated with the attending physician (p < 0.001), positive influenza test (p < 0.001) and diabetes (p = 0.027). Data on complications were available for 351 patients, and 50 (15.8 %) of them reported at least one. Seven patients required hospitalization. Types of complications (pneumonia, bronchitis, etc.) were not significantly different between patients receiving and those not receiving oseltamivir. In the multivariate analysis, higher oseltamivir prescription rate was associated with fewer complications (p < 0.001). Bearing in mind the limitations of a non-randomized study, in a real-life setting, oseltamivir prescription and the rate of complications in patients with influenza were associated with the attending physician, underlying diseases and diagnostic tests. Overall, when the frequency of oseltamivir prescription increased, the influenza-related complications decreased. PMID- 27368994 TI - Genome sequence of a novel mitovirus identified in the phytopathogenic fungus Alternaria arborescens. AB - The phytopathogenic fungus Alternaria spp. contains a variety of double-stranded RNA (dsRNA) elements of different sizes. Detailed analysis of next-generation sequencing data obtained using dsRNA purified from Alternaria arborescens, from which we had previously found Alternaria arborescens victorivirus 1, revealed the presence of another mycoviral-like dsRNA of approximately 2.5 kbp in length. When using the fungal mitochondrial genetic code, this dsRNA has a single open reading frame that potentially encodes an RNA-dependent RNA polymerase (RdRp) with significant to sequence similarity to those of viruses of the genus Mitovirus. Moreover, both the 5'- and 3'-untranslated regions have the potential to fold into stable stem-loop structures, which is characteristic of mitoviruses. Pairwise comparisons and phylogenetic analysis of the deduced amino acid sequences of RdRp indicated that the virus we identified in A. arborescens is a distinct member of the genus Mitovirus in the family Narnaviridae, designated as "Alternaria arborescens mitovirus 1" (AaMV1). PMID- 27368995 TI - [Not Available]. PMID- 27368996 TI - [Not Available]. PMID- 27368997 TI - [Not Available]. PMID- 27368998 TI - [Not Available]. PMID- 27368999 TI - [Not Available]. PMID- 27369000 TI - [Not Available]. PMID- 27369001 TI - [Not Available]. PMID- 27369003 TI - [Not Available]. PMID- 27369002 TI - [Not Available]. PMID- 27369005 TI - [Not Available]. PMID- 27369004 TI - The comparison of the melanin content and UV exposure affecting aging process: seven countries in Asia. AB - BACKGROUND: The skin brightness is determined according to the amount and type of melanin. People with darker skin have a greater amount of melanin that makes their skin less susceptible to UV damages. They live in lower latitude and receive a greater amount of the intensity of the UV radiation. AIM: We wanted to know how the latitude and skin brightness affect skin aging. METHODS: Three thousand volunteers from seven countries (Korea, China, India, Thailand, Vietnam, Indonesia, and Malaysia), aged 20-59 years, participated in this study. We measured skin brightness, Ra (wrinkles parameter), and R2 (elasticity parameter) under controlled environmental conditions. The skin brightness of the face was measured using the Janus(r) which is a facial analysis system. Cutometer(r) the elasticity was measured by on the cheeks, and PRIMOS lite(r) was used to evaluate wrinkles on crow's feet. RESULTS: Latitude and skin brightness showed a positive correlation (0.346). Also, the correlations of Ra and R2 with skin brightness were significantly negative (-0.181) and positive (0.105), respectively. Results of comparison of Ra and R2 with age among the countries showed no significant difference among the 20s, but there was a significant difference among the 50s between countries with high latitude and low latitude. CONCLUSION: The long-term exposure of UV radiation, the natural environmental factor, seems to have more decisive effect on the skin aging process than the photoprotective effect of melanin of epidermal skin. This study helps to understand differences of the skin properties among countries in Asia. PMID- 27369007 TI - [Not Available]. PMID- 27369006 TI - [Not Available]. PMID- 27369008 TI - [Not Available]. PMID- 27369009 TI - [Not Available]. PMID- 27369010 TI - [Not Available]. PMID- 27369011 TI - [Not Available]. PMID- 27369012 TI - [Not Available]. PMID- 27369013 TI - [Not Available]. PMID- 27369014 TI - [Not Available]. PMID- 27369015 TI - [Not Available]. PMID- 27369016 TI - [Not Available]. PMID- 27369017 TI - [Not Available]. PMID- 27369018 TI - [Not Available]. PMID- 27369019 TI - [Not Available]. PMID- 27369020 TI - [Not Available]. PMID- 27369021 TI - [Not Available]. PMID- 27369022 TI - [Not Available]. PMID- 27369023 TI - [Not Available]. PMID- 27369024 TI - Getting Used To It. PMID- 27369026 TI - Engaging Critically Ill Patients in Symptom Management: Thinking Outside the Box! AB - Caring for critically ill patients receiving mechanical ventilation in the intensive care unit (ICU) is an immense challenge for clinicians. Interventions to maintain physiological stability and life itself can cause a number of adverse effects that have a marked impact on patients beyond the period of critical illness or injury. These ICU-acquired conditions include but are not limited to weakness, depression, and post-intensive care syndrome, all of which markedly affect patients' quality of life after they leave the unit. How best to manage the many symptoms experienced by patients undergoing mechanical ventilation without contributing to adverse ICU-acquired sequelae remains a daunting charge for clinicians and requires innovative "out of the box" approaches to address these complex issues. Systematic, cutting-edge research is needed to challenge the "usual" way of managing ICU patients in order to provide the best available evidence for practice integration that minimizes adverse, ICU-acquired sequelae and improves outcomes for the most vulnerable patients. This article highlights a program of research focused on interventions for managing symptoms in critically ill patients receiving mechanical ventilatory support, including the appropriate empowerment of symptom self-management by patients undergoing mechanical ventilation. Development and testing of innovative, nontraditional interventions specifically tailored for ICU patients receiving mechanical ventilatory support are presented. Music listening is highlighted as a nonpharmacological, adjunctive intervention to reduce anxiety associated with mechanical ventilation. Patient controlled sedation is discussed as an alternative method to meet patients' highly individual needs for sedative therapy to promote comfort. PMID- 27369027 TI - Novel Approaches to Symptom Management. PMID- 27369028 TI - Family Presence During Resuscitation: Impact of Online Learning on Nurses' Perception and Self-confidence. AB - BACKGROUND: Family presence during resuscitation (FPDR) is supported by patients and their family members. Nurses, however, including critical care nurses who frequently implement resuscitative care, have mixed views. OBJECTIVES: To determine the impact of online learning on critical care nurses' perception of and self-confidence with FPDR. METHODS: A 2-group, random assignment, pretest and posttest quasi-experimental study was conducted with critical care nurses recruited nationally. An online learning module on FPDR was developed and administered to the intervention group. Perceptions and self-confidence for FPDR were measured by using the Family Presence Risk- Benefit Scale (FPR-BS) and the Family Presence Self-confidence Scale (FPS-CS). Two-factor, mixed-model factorial analysis of variance was used to compare mean scores. RESULTS: A total of 74 critical care nurses participated in the study. Mean FPR-BS and FPS-CS scores were significantly greater in the intervention group than in the control group. For the intervention group, mean scores on the FPR-BS increased from 3.63 to 4.07 (P < .001) and on the FPS-CS increased from 4.24 to 4.57 (P < .001), signifying improved perception and self-confidence. Scores did not change significantly in the control group: mean FPR-BS score increased from 3.82 to 3.88 (P = .23) and the mean FPS-CS score of 4.40 did not change (P > .99). CONCLUSIONS: Online learning is a feasible and effective method for educating large numbers of critical care nurses about FPDR. Online learning can improve perceptions and self confidence related to FPDR, which may promote more widespread adoption of FPDR into practice. PMID- 27369029 TI - A Secure, Social Media-Based "Case of the Month" Module in a Neurocritical Care Unit. AB - BACKGROUND: Systems to meet the on-demand learning needs of nurses in intensive care units are not well studied beyond the traditional classroom models. OBJECTIVE: To study the feasibility and effect of implementing an online discussion forum for nurses in a busy neuroscience intensive care unit. METHODS: A baseline survey was done to highlight the areas of educational need in the unit. Freeform-a password-protected, online discussion forum supported by the university-was used for the pilot project. Freeform has functions similar to Facebook, with "likes," "follow," discussion/comment spaces, and the capacity for uploading images and files. A page called "All things NeuroCritical Care" was created. All nurses working in the intensive care unit were automatically enrolled. Clinical vignettes relevant to neurocritical care were posted once a month with 1 to 2 lead questions. All participation was voluntary, and topics were chosen on the basis of the needs survey. At the end of each case, a recent review article on the topic was posted for secure download. RESULTS: Eight sentinel diagnoses have been presented as clinical vignettes, and 34 of 76 members formally follow the page. The mean number of discussion strings per case is 8.3 posts. The number of unique visitors to the page during active case discussions exceeds 100. CONCLUSION: A secure, online, problem-based learning discussion format is a feasible point-of-care learning opportunity that can help overcome some of the traditional barriers to ongoing nursing education needs in a busy intensive care unit. PMID- 27369030 TI - Clinical Outcomes of Inadequate Calorie Delivery and Protein Deficit in Surgical Intensive Care Patients. AB - BACKGROUND: Adequate nutritional therapy in critically ill patients is integral to optimal outcome. OBJECTIVE: To evaluate the association between cumulative macronutrient deficit and overall morbidity in surgical intensive care unit patients. METHODS: Adult patients receiving enteral nutrition for more than 72 hours were included if they had no previous admission to the surgical intensive care unit, had received no enteral feedings before admission, had no intestinal obstruction or ileus, and survived 72 hours or more after admission. Data on demographics, outcomes, and nutritional intake during the unit stay were collected for up to 14 days until oral intake began, discharge, or death. Outcome variables included lengths of stay in the hospital and intensive care unit, days with no mechanical ventilation, complications, and mortality. RESULTS: Of 94 participants, 71% were men, mean age was 63 years, and mean score on the Acute Physiology and Chronic Health Evaluation II was 14. Patients with high cumulative calorie deficit (>= 6000 cal) and high protein deficit (>= 300 g) had significantly fewer days with no mechanical ventilation (P < .001), longer unit stays (P < .001), longer hospital stays (P = .007), more total complications (P = .007), and more infectious complications (P = .009) than other participants. These associations remained significant in multivariable models after adjustments for age, sex, reason for admission, and propensity score of deficit. In-hospital and 30-day mortality did not differ. CONCLUSIONS: Cumulative macronutrient deficits have important clinical outcomes in surgical intensive care patients. PMID- 27369031 TI - Association of Injury Factors, Not Body Mass Index, With Hospital Resource Usage in Trauma Patients. AB - BACKGROUND: Allocating resources appropriately requires knowing whether obese patients use more resources during a hospital stay than nonobese patients. OBJECTIVES: To determine if trauma patients with different body mass indexes differed in use of resources measured as a multifaceted outcome variable. METHODS: A trauma registry was used for a retrospective study of adult patients admitted to a midwestern level I trauma center. Patients were stratified into 3 groups: nonobese (normal weight, overweight), obese, and morbidly obese. Three canonical correlation analyses were used to determine the relationship between patient/injury characteristics and hospital resource usage. RESULTS: In a sample of 9771 patients, 71.2% were non-obese, 23.8% obese, and 5.0% morbidly obese. For patient/injury characteristics, Injury Severity Score and physiological complications were significant variables for all 3 groups. Scores on the Glasgow Coma Scale were significant for nonobese patients only. For resource usage, intensive care unit length of stay and procedures were significant variables for all 3 groups. CONCLUSIONS: Associations between body mass index and outcomes have been noted when assessed as independent variables. However, when resource usage was assessed as a multifaceted outcome variable, injury factors (higher Injury Severity Score, lower scores on the Glasgow Coma Scale, more physiological complications) were associated with resource usage (increased length of stay in the intensive care unit and increased number of procedures). These findings provide clinicians a new perspective for evaluating the complex relationship between patient/injury characteristics and hospital resource usage. PMID- 27369032 TI - Improving Providers' Role Definitions to Decrease Overcrowding and Improve In Hospital Cardiac Arrest Response. AB - BACKGROUND: How nontechnical factors such as inadequate role definition and overcrowding affect outcomes of in-hospital cardiac arrest (IHCA) is unknown. Using a bundled intervention, we sought to improve providers' role definitions and decrease overcrowding during IHCA events. OBJECTIVES: To determine if a bundled intervention consisting of a nurse/physician leadership dyad, visual cues for provider roles, and a "role check" would lead to reductions in crowding and improve perceptions of communication and team leadership. METHODS: Baseline data on the number and type of IHCA providers were collected. Providers were asked to complete a postevent survey rating communication and leadership. A bundled intervention was then introduced. Data were then obtained for the subsequent IHCA events. RESULTS: Twenty ICHA events were captured before and 34 after the intervention. The number of physicians present at pulse checks 2 (median [interquartile range]: 6 [5-8] before vs 5 [3-6] after, P = .02) and 3 (7 [5-9] vs 4 [4-5], P = .004) decreased significantly after the intervention. The overall number of providers at the third pulse check (18 [14-22] before vs 14 [12-16] after, P = .04) also decreased after the intervention. On a 10-point Likert scale, ratings of communication (8 [7-8]) and physician leadership (8 [7-9]) did not differ significantly from before to after the intervention. Both the physician leads (90%) and patients' primary nurses (97%) were able to identify clear nurse leaders. CONCLUSION: A bundled intervention targeted at improving IHCA response led to a decrease in overcrowding at ICHA events without substantial changes in the perceptions of communication or physician leadership. PMID- 27369033 TI - Usability Testing of an Electronic Patient-Reported Outcome System for Survivors of Critical Illness. AB - BACKGROUND: Web-based electronic patient-reported outcomes (ePRO) measures are increasingly used to facilitate patient-centered health assessments. However, it is unknown if ePRO completion is feasible for recently ill intensive care unit (ICU) survivors and their families. OBJECTIVE: To develop and evaluate the usability of a novel ePRO system (ePRO to Support People and Enhance Recovery [ePROSPER]) among ICU survivors and their families within an ongoing clinical trial. METHODS: Paper-based PROs were iteratively adapted to electronic forms (ePROs). Then, the usability of ePROSPER was assessed among 60 patients, their family members, and PRO and programming experts via questionnaires (eg, Systems Usability Scale), "think aloud" open-ended feedback, task completion times, and error rates. RESULTS: Input from patients and their families was used to incorporate user-experience modifications into ePROSPER. This feedback also led to inclusion of automated reminders for questionnaire completion and real-time alerts for staff triggered by high symptom levels. Median usability scores increased over testing cycles from 40 to 73 to 95, nearing the maximum score and showing excellent usability. All users completed ePROSPER within 20 minutes; 87% preferred it to a written version. ePROSPER was then implemented in a clinical trial without data errors. CONCLUSIONS: Automated ePRO systems can be successfully integrated in a post-ICU clinical trial setting. The value of integrating such systems in direct clinical care should be assessed in future studies. PMID- 27369034 TI - Living with Dying in the Pediatric Intensive Care Unit: A Nursing Perspective. AB - BACKGROUND: Despite reported challenges encountered by nurses who provide palliative care to children, few researchers have examined this phenomenon from the perspective of nurses who care for children with life-threatening illnesses in pediatric intensive care units. OBJECTIVES: To describe and interpret the essence of the experiences of nurses in pediatric intensive care units who provide palliative care to children with life-threatening illnesses and the children's families. METHODS: A hermeneutic phenomenological study was conducted with 12 pediatric intensive care unit nurses in the northeastern United States. Face-to-face interviews and field notes were used to illuminate the experiences. RESULTS: Five major themes were detected: journey to death; a lifelong burden; and challenges delivering care, maintaining self, and crossing boundaries. These themes were illuminated by 12 subthemes: the emotional impact of the dying child, the emotional impact of the child's death, concurrent grieving, creating a peaceful ending, parental burden of care, maintaining hope for the family, pain, unclear communication by physicians, need to hear the voice of the child, remaining respectful of parental wishes, collegial camaraderie and support, and personal support. CONCLUSION: Providing palliative care to children with life threatening illnesses was complex for the nurses. Findings revealed sometimes challenging intricacies involved in caring for dying children and the children's families. However, the nurses voiced professional satisfaction in providing palliative care and in support from colleagues. Although the nurses reported collegial camaraderie, future research is needed to identify additional supportive resources that may help staff process and cope with death and dying. PMID- 27369035 TI - Credentialing and Privileging of Acute Care Nurse Practitioners to Do Invasive Procedures: A Statewide Survey. AB - BACKGROUND: Acute care nurse practitioners have been successfully integrated into inpatient settings. They perform invasive procedures in the intensive care unit and other acute care settings. Although their general scope of practice is regulated at the state level, local and regional scope of practice is governed by hospitals. OBJECTIVE: To determine if credentialing and privileging of these nurses for invasive procedures varies depending on the institution. METHODS: Personnel in medical staff offices of 329 hospitals were surveyed by telephone with 6 questions. Data collected included acute care nurse practitioner and hospital demographics, frequency and type of procedures performed, proctoring and credentialing process, and the presence of residents and fellows at the institution. RESULTS: The response rate was 74.8% (246 hospitals). Among these, 48% (118) employed acute care nurse practitioners, of which 43.2% performed invasive procedures. Three hospitals were excluded from the final analysis. Of the hospitals that credentialed and granted privileges to the nurse practitioners for invasive procedures, 60.4% were teaching hospitals. A supervising physician was the proctor in 94% of the nonteaching hospitals and 100% of the teaching hospitals. The most common number of cases proctored was 4 to 7. CONCLUSION: The majority of hospitals employ acute care nurse practitioners. The most common method of privileging for invasive procedures is proctoring by a supervising physician. However, the amount of proctoring required before privileges and independent practice are granted varies by procedure and institution. PMID- 27369036 TI - Evidence-Based Review and Discussion Points. PMID- 27369037 TI - Long-Term Acute Care: Where Does It Fit in the Health Care Continuum? PMID- 27369038 TI - An Official Critical Care Societies Collaborative Statement: Burnout Syndrome in Critical Care Health Care Professionals: A Call for Action. AB - Burnout syndrome (BOS) occurs in all types of health care professionals and is especially common in individuals who care for critically ill patients. The development of BOS is related to an imbalance of personal characteristics of the employee and work-related issues or other organizational factors. BOS is associated with many deleterious consequences, including increased rates of job turnover, reduced patient satisfaction, and decreased quality of care. BOS also directly affects the mental health and physical well-being of the many critical care physicians, nurses, and other health care professionals who practice worldwide. Until recently, BOS and other psychological disorders in critical care health care professionals remained relatively unrecognized. To raise awareness of BOS, the Critical Care Societies Collaborative (CCSC) developed this call to action. The present article reviews the diagnostic criteria, prevalence, causative factors, and consequences of BOS. It also discusses potential interventions that may be used to prevent and treat BOS. Finally, we urge multiple stakeholders to help mitigate the development of BOS in critical care health care professionals and diminish the harmful consequences of BOS, both for critical care health care professionals and for patients. PMID- 27369039 TI - Differential Diagnoses for Suspected ACS. PMID- 27369040 TI - A Fatal Case of Eczema Herpeticum With Septic Shock Due to Methicillin-Resistant Staphylococcus aureus. AB - A 62-year-old woman treated with several courses of corticosteroids for an undifferentiated rash came to the emergency department with progressively worsening cutaneous signs and symptoms and generalized weakness. She had scabies, and despite treatment continued to decompensate. Repeat skin biopsies revealed disseminated herpes simplex virus infection, and results of blood cultures were consistent with infection by methicillin-resistant Staphylococcus aureus. Despite antiviral and antimicrobial therapy, sepsis and multiorgan failure developed, and the patient died. This case illustrates the complications of the rare entity eczema herpeticum, which occurs most often in immunocompromised patients and is associated with a high mortality. Maintaining a high index of suspicion for this disease in decompensating patients with an unidentified rash is essential to avoid catastrophic outcomes. PMID- 27369042 TI - Multidisciplinary Review of Code Events in a Heart Center. AB - OBJECTIVE: To identify a cause for clinical deterioration, examine resuscitation efforts, and identify and correct system issues (thus improving outcomes) via a multidisciplinary code-review process soon after cardiopulmonary arrest. METHODS: Retrospective analysis of code events in a tertiary pediatric heart center from September 2010 to December 2013 and review of surgical-cardiac data from January 2010 to December 2013. RESULTS: A multidisciplinary team reviewed 47 code events, 16 of which (34%) were deemed potentially preventable. At least 2 issues were identified during 66% (31/47) of cardiopulmonary arrests reviewed. Key issues identified were related to communication (62%), environment/culture/policy (47%), patient care (including resuscitation, 41%), and equipment (38%). About 60% of reviewed arrests resulted in educational initiatives (eg, mock code, in-service education) and 47% resulted in a new policy or modification of existing policy. Less common were changes in equipment (32%) or modification of staffing needs (11%). Changes most frequently occurred in the unit specific to the event (68%) but some changes occurred throughout the Heart Center (32%) or across the hospital system (13%). Survival to discharge after cardiopulmonary arrest has improved over time (P = .03) to 81% for cardiac surgical patients in our center. CONCLUSION: A multidisciplinary code-review committee can identify deficiencies and lead to educational initiatives and improvements in care. When coupled with a hospital-wide "code blue" review process, these changes may benefit the institution as a whole. PMID- 27369041 TI - Delirium in Survivors of Cardiac Arrest Treated With Mild Therapeutic Hypothermia. AB - BACKGROUND: Mild therapeutic hypothermia is recommended for comatose patients resuscitated from cardiac arrest. However, the prevalence of delirium and its associated risk factors have not been assessed in survivors of cardiac arrest treated with therapeutic hypothermia. OBJECTIVE: To determine the prevalence of and risk factors for delirium among survivors of cardiac arrest who were treated with therapeutic hypothermia. METHODS: A retrospective observational study of patients treated with therapeutic hypothermia after cardiac arrest from 2007 through 2014. Baseline demographic data and daily delirium assessments throughout the intensive care unit stay were obtained. The association between duration of delirium and various risk factors was assessed. RESULTS: Of 251 patients, 107 (43%) awoke from coma. Among the 107 survivors, all had at least 1 day of delirium during their intensive care unit stay. Median number of days of delirium was 4.0 (interquartile range, 2.0-7.5). Multivariable analysis revealed that age (odds ratio, 1.72; 95% CI, 1.0-2.95; P = .05), time from cardiopulmonary resuscitation to return of spontaneous circulation (odds ratio 1.52; 95% CI, 1.11 2.07; P = .01), and total dose of prewarming propofol (odds ratio, 0.02; 95% CI, 0.00-0.48; P = .02) were associated with duration of delirium. CONCLUSIONS: All survivors of cardiac arrest treated with mild therapeutic hypothermia had at least 1 day of delirium. Age and time from initiation of cardiopulmonary resuscitation to return of spontaneous circulation were associated with prolonged delirium, whereas exposure to propofol was protective against delirium. These findings are limited to this unique cohort and may not be generalizable to different populations. PMID- 27369043 TI - An optimized multiplex flow cytometry protocol for the analysis of intracellular signaling in peripheral blood mononuclear cells. AB - Phosphoflow cytometry is increasingly being used as a tool for the discovery of biomarkers used in the treatment and monitoring of disease and therapy. The ability to measure numerous phospho-protein targets simultaneously at a single cell level accurately and rapidly provides significant advantages over other methods. We here discuss important considerations required to successfully implement these methods. Three different blood collection tubes (lithium-heparin tubes, CPT with sodium citrate and CPT with sodium heparin) were evaluated, with PBMC isolated through lithium-heparin tubes/lymphoprep displaying reduced basal and increased stimulation induced phosphorylation compared to the other two methods. Further, we provide a protocol outlining an 8 color assay developed for the study of intracellular signaling in peripheral blood mononuclear cells. The assay allows for the quantitative measurement of the phospho-proteins ERK1/2, NF kappaB p65, Stat1 (Y701), Stat1 (S727), Stat3 (Y705), Stat3 (S727), Stat4 (Y693), p38 and Stat5 (Y694), as well as the identification of T cells, B cells, natural killer cells and monocytes. The assay additionally incorporates fluorescent cell barcoding, reducing assay costs and increasing throughput while increasing data robustness. Inter-assay precision was assessed over a month long period for all experimental variables (phospho-protein measured, cell type and stimulant). Coefficient of variations (CVs) calculated from process triplicates of normalized median fluorescence intensity (MFI) of the phospho-proteins displayed median CVs under 10% when grouped according to cell type, stimulation agent and phospho protein measured, while the CV for each triplicate did not exceed 20%. PMID- 27369044 TI - Randomized Controlled Theory-Based, E-Mail-Mediated Walking Intervention. AB - The purpose of this study was to evaluate the ability of two concurrent randomized controlled interventions based on social cognitive theory to increase walking. A second purpose was to compare the efficacy of the intervention between two distinct groups: dog owners and non-dog owners. Adult dog owners ( n = 40) and non-dog owners ( n = 65) were randomized into control or intervention groups. Intervention groups received bi-weekly emails for first 4 weeks and then weekly email for the next 8 weeks targeting self-efficacy, social support, goal setting, and benefits/barriers to walking. Dog owner messages focused on dog walking while non-dog owners received general walking messages. Control groups received a 1 time email reviewing current physical activity guidelines. At 6 months, both intervention groups reported greater increases in walking and maintained these increases at 12 months. The greatest increases were seen in the dog owner intervention group. In conclusion, dog owners accumulated more walking, which may be attributed to the dog-owner relationship. PMID- 27369047 TI - Enhancing PD-1 Blockade in Solid Tumors. AB - A phase I study indicates that the combination of utomilumab, an investigational antibody that binds CD137, plus pembrolizumab is safe and well tolerated, yielding sustained responses in patients with various solid cancers. PMID- 27369051 TI - Comparison of image quality and patient discomfort in prostate MRI: pelvic phased array coil vs. endorectal coil. AB - PURPOSE: To compare image quality (IQ) and patient discomfort during prostate MRI using a pelvic phased array (PPA) coil and an endorectal (ER) coil. MATERIALS AND METHODS: Ninety-eight patients (median age, 65.7; range 42.1-78.1) underwent prostate MRI on a 3T scanner including T2w and DWI acquired with PPA and an ER coil within the same exam. Acquisition time was kept similar for both acquisitions. Two radiologists evaluated aspects of IQ on a 5-point Likert scale and classified image artifacts. All patients completed a questionnaire on discomfort/pain regarding the ER coil using a visual analogue scale from 1 to 10. RESULTS: There was no significant difference in overall IQ for T2w images for both readers (reader 1, 3.27 +/- 0.91 and 3.07 +/- 0.84, p = 0.057; reader 2, 3.70 +/- 0.75 and 3.77 +/- 0.81, p = 0.555) for PPA and ER coils, respectively. Overall IQ for DWI acquired with PPA and ER coils was rated similar by reader 1 (3.03 +/- 1.10 and 3.08 +/- 0.80, respectively, (p = 0.67)), while reader 2 preferred ER coil images (3.27 +/- 0.81 and 3.66 +/- 0.85 (p < 0.05)). Susceptibility artifacts were more frequent in ER than in PPA coil images (109 vs. 75). Discomfort and pain experienced during insertion of the ER coil was low altogether (VAS score, 3.5 +/- 2.1 for "discomfort" and 2.4 +/- 2.4 for "pain"). CONCLUSION: T2-weighted images may be acquired with comparable IQ using a PPA coil as compared to an ER coil, while DWI images showed better IQ using the ER coil for one of two readers. The insertion of the ER coil caused low to moderate discomfort and pain in patients. PMID- 27369050 TI - Protection against vascular leak in neprilysin transgenic mice with complex overexpression pattern. AB - Neprilysin (NEP) is a cell surface metallopeptidase found in many tissues. Based mostly on pharmacological manipulations, NEP has been thought to protect blood vessels from plasma extravasation. We have suggested that NEP may protect against pulmonary vascular injury. However, these prior studies did not utilize mice which overexpress NEP. The aims of the present investigation were to develop and characterize doubly transgenic (DT) mice that overexpress NEP universally and conditionally, and to investigate the protective effect that overexpressed NEP may have against plasma extravasation in the vasculature. The duodenum, which is often used to assess vascular permeability, and in which the NEP protein was overexpressed in our DT mice two-fold, was selected as our experimental preparation. We found that substance P-induced plasma extravasation was decreased substantially (3.5-fold) in the duodenums of our doxycycline-treated DT mice, giving independent evidence of NEP's protective effects against plasma extravasation. Transgenic lung NEP protein was not stably expressed in the DT mice, so we were not able to test the effect of NEP overexpression in the lung. Although initially overexpressed nearly nine-fold at that site, pulmonary NEP protein overexpression eventually dissipated. Surprisingly, at a time when there was no lung transgenic NEP protein overexpression, lung NEP mRNA expression was still increased 23-fold, indicating that the expression defect probably is not transcriptional. These studies help to characterize our complex transgenic model of NEP overexpression and further demonstrate NEP's protective effects against plasma extravasation. PMID- 27369052 TI - [Not Available]. PMID- 27369053 TI - [Not Available]. PMID- 27369054 TI - [Not Available]. PMID- 27369056 TI - [Not Available]. PMID- 27369055 TI - [Not Available]. PMID- 27369057 TI - [Not Available]. PMID- 27369058 TI - [Not Available]. PMID- 27369059 TI - [Not Available]. PMID- 27369060 TI - [Not Available]. PMID- 27369062 TI - [Not Available]. PMID- 27369061 TI - [Not Available]. PMID- 27369063 TI - [Not Available]. PMID- 27369064 TI - [Not Available]. PMID- 27369065 TI - [Not Available]. PMID- 27369066 TI - Amygdala functional connectivity as a longitudinal biomarker of symptom changes in generalized anxiety. AB - Generalized anxiety disorder (GAD) is characterized by excessive worry, autonomic dysregulation and functional amygdala dysconnectivity, yet these illness markers have rarely been considered together, nor their interrelationship tested longitudinally. We hypothesized that an individual's capacity for emotion regulation predicts longer-term changes in amygdala functional connectivity, supporting the modification of GAD core symptoms. Sixteen patients with GAD (14 women) and individually matched controls were studied at two time points separated by 1 year. Resting-state fMRI data and concurrent measurement of vagally mediated heart rate variability were obtained before and after the induction of perseverative cognition. A greater rise in levels of worry following the induction predicted a stronger reduction in connectivity between right amygdala and ventromedial prefrontal cortex, and enhanced coupling between left amygdala and ventral tegmental area at follow-up. Similarly, amplified physiological responses to the induction predicted increased connectivity between right amygdala and thalamus. Longitudinal shifts in a distinct set of functional connectivity scores were associated with concomitant changes in GAD symptomatology over the course of the year. Results highlight the prognostic value of indices of emotional dysregulation and emphasize the integral role of the amygdala as a critical hub in functional neural circuitry underlying the progression of GAD symptomatology. PMID- 27369067 TI - Temporal voice areas exist in autism spectrum disorder but are dysfunctional for voice identity recognition. AB - The ability to recognise the identity of others is a key requirement for successful communication. Brain regions that respond selectively to voices exist in humans from early infancy on. Currently, it is unclear whether dysfunction of these voice-sensitive regions can explain voice identity recognition impairments. Here, we used two independent functional magnetic resonance imaging studies to investigate voice processing in a population that has been reported to have no voice-sensitive regions: autism spectrum disorder (ASD). Our results refute the earlier report that individuals with ASD have no responses in voice-sensitive regions: Passive listening to vocal, compared to non-vocal, sounds elicited typical responses in voice-sensitive regions in the high-functioning ASD group and controls. In contrast, the ASD group had a dysfunction in voice-sensitive regions during voice identity but not speech recognition in the right posterior superior temporal sulcus/gyrus (STS/STG)-a region implicated in processing complex spectrotemporal voice features and unfamiliar voices. The right anterior STS/STG correlated with voice identity recognition performance in controls but not in the ASD group. The findings suggest that right STS/STG dysfunction is critical for explaining voice recognition impairments in high-functioning ASD and show that ASD is not characterised by a general lack of voice-sensitive responses. PMID- 27369068 TI - Network integrity of the parental brain in infancy supports the development of children's social competencies. AB - The cross-generational transmission of mammalian sociality, initiated by the parent's postpartum brain plasticity and species-typical behavior that buttress offspring's socialization, has not been studied in humans. In this longitudinal study, we measured brain response of 45 primary-caregiving parents to their infant's stimuli, observed parent-infant interactions, and assayed parental oxytocin (OT). Intra- and inter-network connectivity were computed in three main networks of the human parental brain: core limbic, embodied simulation and mentalizing. During preschool, two key child social competencies were observed: emotion regulation and socialization. Parent's network integrity in infancy predicted preschoolers' social outcomes, with subcortical and cortical network integrity foreshadowing simple evolutionary-based regulatory tactics vs complex self-regulatory strategies and advanced socialization. Parent-infant synchrony mediated the links between connectivity of the parent's embodied simulation network and preschoolers' ability to use cognitive/executive emotion regulation strategies, highlighting the inherently dyadic nature of this network and its long-term effects on tuning young to social life. Parent's inter-network core limbic-embodied simulation connectivity predicted children's OT as moderated by parental OT. Findings challenge solipsistic neuroscience perspectives by demonstrating how the parent-offspring interface enables the brain of one human to profoundly impact long-term adaptation of another. PMID- 27369070 TI - Long-term follow-up and management of small and medium-sized CD4+ T cell lymphoma and CD8+ lymphoid proliferations of acral sites: a multicenter experience. AB - BACKGROUND: Primary cutaneous CD4+ small-medium pleomorphic T cell lymphoma (SMPTCL) is a low-grade cutaneous T cell lymphoma. Its clinical and histopathologic features are comparable with those of CD8+ lymphoid proliferations (LPs) of the ear and acral sites. OBJECTIVES: We performed a retrospective analysis of patients with CD4+ SMPTCL or CD8+ LP to elucidate the clinical course, prognosis, and outcomes. METHODS: Demographic, clinical, and treatment data were reviewed. Histopathologic data based on architectural, cytomorphologic, and immunohistochemical features were assessed. Immunohistochemical staining for T and B cell markers was evaluated. RESULTS: A total of 25 patients including 22 with CD4+ SMPTCL and three with CD8+ LP were identified. All patients presented with a single lesion, predominantly on the head, neck, or upper trunk (84%). No patients showed extracutaneous disease at any evaluation. The most common histopathologic changes showed a dense nodular infiltrate of small cells with hyperchromatic nuclei without significant follicular or adnexal involvement. Patients were treated with excision (48%), local radiation (28%), or topical or intralesional steroids (24%). All patients achieved complete resolution of disease. Five patients demonstrated cutaneous relapse at new sites. CONCLUSIONS: The CD4+ SMPTCL/CD8+ LP subgroup usually presents with solitary lesions and demonstrates an indolent clinical course. Typical presentation, classic histopathology, widespread expression of follicular T helper cell markers, and loss of a T cell antigen are diagnostic features of CD4+ SMPTCL, whereas monomorphous CD8+ infiltrate without follicular T helper cell markers is consistent with CD8+ LP. Local skin-directed therapy is appropriate in these patients. PMID- 27369069 TI - The neural basis of improved cognitive performance by threat of shock. AB - Anxiety can have both detrimental and facilitatory cognitive effects. This study investigates the neural substrates of a replicated facilitatory effect of anxiety on sustained attention and response inhibition. This effect consisted of improved performance on the Sustained Attention to Response Task (a Go-NoGo task consisting of 91% Go and 9% NoGo trials) in threat (unpredictable electrical shock) vs safe (no shock) conditions. This study uses the same experimental design with fMRI and relies on an event-related analysis of BOLD signal changes. Findings reveal that threat-related cognitive facilitation (improved NoGo accuracy) is associated with greater activation of a right-lateralized frontoparietal group of regions previously implicated in sustained attention and response inhibition. Moreover, these same regions show decreased activation in the Go trials preceding NoGo errors. During NoGo trials, striatal activity is also greater in the threat vs safe condition, consistent with the notion of enhanced inhibitory processing under threat. These findings identify potential mechanisms by which threat of unpredictable shock can facilitate distinct cognitive functions. A greater understanding of the complex interaction of the anxious state and cognitive processes may have critical clinical implications. PMID- 27369071 TI - Functional characterization of Helicobacter pylori 26695 sedoheptulose 7 phosphate isomerase encoded by hp0857 and its association with lipopolysaccharide biosynthesis and adhesion. AB - Helicobacter pylori is a notorious human pathogen and the appearance of antibiotic resistance of this bacterium has posed a serious threat to human health. Lipopolysaccharide (LPS) is a key virulence factor and plays important roles in pathogenesis of H. pylori infection. Sedoheptulose 7-phosphate isomerase (GmhA), as an enzyme participating in the first step of heptose biosynthesis, is indispensable for the formation of inner core oligosaccharide of LPS. In this study, we cloned one putative gmhA ortholog, hp0857, from H. pylori 26695 and overexpressed it in Eschericha coli. Based on the results of molecular weight determination, the recombinant HP0857 is likely a homodimer. Analysis of enzymatic kinetic properties of this protein confirmed that hp0857 is indeed encoded a phosphoheptose isomerase which can utilize sedoheptulose 7-phosphate as the substrate in the ADP-L-glycero-D-manno-heptose (ADP- L,D-Hep) biosynthesis pathway. We also generated an HP0857 knockout mutant and explored its phenotypic changes. This mutant exhibited a decreased growth rate and displayed a "deep rough" type of LPS structure. In addition, it also had a slight decrease in its motility and was more susceptible to hydrophobic antibiotic novobiocin and detergents Triton X-100 and SDS. Furthermore, the adhesive capacity of the HP0857 knockout mutant to AGS cells was reduced significantly, and most of the infected cells didn't show a classic hummingbird phenotype. However, complementation of the HP0857 knockout mutation restored most of these phenotypic changes. In conclusion, we demonstrated that HP0857 protein is essential for inner core biosynthesis of H. pylori LPS and is a potential target for developing new antimicrobial agents against H. pylori infection. PMID- 27369072 TI - LXR agonist rescued the deficit in the proliferation of the cerebellar granule cells induced by dexamethasone. AB - Dexamethasone (DEX) exposure during early postnatal life produces permanent neuromotor and intellectual deficits and stunts cerebellar growth. The liver X receptor (LXR) plays important roles in CNS development. However, the effects of LXR on the DEX-mediated impairment of cerebellar development remain undetermined. Thus, mice were pretreated with LXR agonist TO901317 (TO) and were later exposed to DEX to evaluate its protective effects on DEX-mediated deficit during cerebellar development. The results showed that an acute exposure of DEX on postnatal day 7 resulted in a significant impairment in cerebellar development and decreased the proliferation of granule neuron precursors in the external granule layer of cerebellum. This effect was attenuated by pretreatment with TO. We further found that the decrease in the proliferation caused by DEX occurred via up-regulation of glucocorticoid receptor and p27kip1, which could be partially prevented by LXR agonist pretreatment. Overall, our results suggest that LXR agonist pretreatment could protect against DEX-induced deficits in cerebellar development in postnatal mice and may thus be perspective recruited to counteract such GC side effects. PMID- 27369073 TI - Ca(2+)/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) interacts with neurofilament L and inhibits its filament association. AB - Ca(2+)/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) is a Ser/Thr phosphatase that belongs to the PPM family. Growing evidence suggests that PPM phosphatases including CaMKP act as a complex with other proteins to regulate cellular functions. In this study, using the two-dimensional far-western blotting technique with digoxigenin-labeled CaMKP as a probe, in conjunction with peptide mass fingerprinting analysis, we identified neurofilament L (NFL) as a CaMKP binding protein in a Triton-insoluble fraction of rat brain. We confirmed binding of fluorescein-labeled CaMKP (F-CaMKP) to NFL in solution by fluorescence polarization. The analysis showed that the dissociation constant of F-CaMKP for NFL is 73 +/- 17 nM (n = 3). Co-immunoprecipitation assay using a cytosolic fraction of NGF-differentiated PC12 cells showed that endogenous CaMKP and NFL form a complex in cells. Furthermore, the effect of CaMKP on self-assembly of NFL was examined. Electron microscopy revealed that CaMKP markedly prevented NFL from forming large filamentous aggregates, suggesting that CaMKP-binding to NFL inhibits its filament association. These findings may provide new insights into a novel mechanism for regulating network formation of neurofilaments during neuronal differentiation. PMID- 27369074 TI - Structural and functional insight into the N-terminal domain of the clathrin adaptor Ent5 from Saccharomyces cerevisiae. AB - Clathrin-coated vesicles (CCVs) play critical roles in multiple cellular processes, including nutrient uptake, endosome/lysosome biogenesis, pathogen invasion, regulation of signalling receptors, etc. Saccharomyces cerevisiae Ent5 (ScEnt5) is one of the two major adaptors supporting the CCV-mediated TGN/endosome traffic in yeast cells. However, the classification and phosphoinositide binding characteristic of ScEnt5 remain elusive. Here we report the crystal structures of the ScEnt5 N-terminal domain, and find that ScEnt5 contains an insertion alpha' helix that does not exist in other ENTH or ANTH domains. Furthermore, we investigate the classification of ScEnt5-N(31-191) by evolutionary history analyses and structure comparisons, and find that the ScEnt5 N-terminal domain shows different phosphoinositide binding property from rEpsin1 and rCALM. Above results facilitate the understanding of the ScEnt5-mediated vesicle coat formation process. PMID- 27369075 TI - Involvement of the MEK/ERK pathway in EGF-induced E-cadherin down-regulation. AB - E-cadherin is a major component of the epithelial adherens junction. However, the regulatory mechanism of E-cadherin expression is still poorly understood. In this study, we found that EGF decreased E-cadherin expression at both mRNA and protein levels in colorectal carcinoma LoVo cells. Since E-cadherin down-regulation is a well-known hallmark of the EMT (Epithelial-Mesenchymal Transition), we investigated whether EGF induced E-cadherin down-regulation during the EMT. EGF was unable to affect the expression of mesenchymal markers (such as N-cadherin, vimentin or fibronectin) or EMT-regulating transcription factors (such as SNAIL, SLUG, ZEB1, ZEB2 or TWIST), suggesting that EGF induced E-cadherin down regulation via an EMT-independent mechanism. On the other hand, the MEK inhibitor U0126 was found to suppress EGF-induced E-cadherin down-regulation at the transcriptional level, suggesting that the MEK/ERK pathway is involved in EGF induced E-cadherin down-regulation. Moreover, we also found that EGF disrupted cell-cell contact, stimulated cells to form an elongated shape with filamentous protrusions, and induced cell migration in LoVo cells. These effects were suppressed by U0126. Therefore, EGF is suggested to induce E-cadherin down regulation at the transcriptional level through the MEK/ERK pathway, which might result in, at least in part, the induction of cellular morphological changes and cell migration in LoVo cells. PMID- 27369076 TI - Involvement of the T-box transcription factor Brachyury in early-stage embryonic mouse salivary gland. AB - The mouse submandibular gland (SMG) is important organ for embryonic development, and branching morphogenesis is regulated by many molecules containing transcription factors. Real-time reverse transcriptase polymerase chain reaction revealed that the expression of Brachyury increased in the SMG and peaked between E12.5-E13.5, concomitant with the early stage of branching morphogenesis. The expression of Brachyury in SMG rudiments between E12.5-E13.5 was confirmed by western blotting. In addition, fibronectin and Btbd7 (regulated by fibronectin), which are both essential for cleft formation, were expressed strongly during the same period. The Sox2 and Wnt3a, which regulate cell growth, were also expressed strongly during E12.5-E13.5. On the other hand, cleft formation and branching morphogenesis was suppressed by knockdown of Brachyury gene, suggesting that Brachyury plays a central role in regulating cell growth and cleft formation in early-stage embryonic mouse salivary gland development. PMID- 27369077 TI - The role of receptor topology in the vitamin D3 uptake and Ca(2+) response systems. AB - The steroid hormone, vitamin D3, regulates gene transcription via at least two receptors and initiates putative rapid response systems at the plasma membrane. The vitamin D receptor (VDR) binds vitamin D3 and a second receptor, importin-4, imports the VDR-vitamin D3 complex into the nucleus via nuclear pores. Here we present evidence that the Homo sapiens VDR homodimer contains two transmembrane (TM) helices ((327)E - D(342)), two TM "half-helix" ((264)K N(276)), one or more large channels, and 16 cholesterol binding (CRAC/CARC) domains. The importin-4 monomer exhibits 3 pore-lining regions ((226)E - L(251); (768)V - G(783); (876)S A(891)) and 16 CRAC/CARC domains. The MEMSAT algorithm indicates that VDR and importin-4 may not be restricted to cytoplasm and nucleus. VDR homodimer TM helix topology predicts insertion into the plasma membrane, with two 84 residue C terminal regions being extracellular. Similarly, MEMSAT predicts importin-4 insertion into the plasma membrane with 226 residue extracellular N-terminal regions and 96 residue C-terminal extracellular loops; with the pore-lining regions contributing gated Ca(2+) channels. The PoreWalker algorithm indicates that, of the 427 residues in each VDR monomer, 91 line the largest channel, including two vitamin D3 binding sites and residues from both the TM helix and "half-helix". Cholesterol-binding domains also extend into the channel within the ligand binding region. Programmed changes in bound cholesterol may regulate both membrane Ca(2+) response systems and vitamin D3 uptake as well as receptor internalization by the endomembrane system culminating in uptake of the vitamin D3-VDR-importin-4 complex into the nucleus. PMID- 27369078 TI - Conversion of neural plate explants to pre-placodal ectoderm-like tissue in vitro. AB - Neural crest and cranial sensory placodes arise from ectodermal epithelium lying between the neural plate and non-neural ectoderm (neural border). BMP signaling is important for both an induction of the neural border and a subsequent induction of the neural crest within the neural border. In contrast, FGF signaling is important for the neural border induction and the following induction of the pre-placodal ectoderm (PPE), which later gives rise to the cranial sensory placodes. While previous studies have demonstrated that the neural plate explants could be converted to the neural crest cells by adding BMP4 in a culture medium, there is no report showing a similar conversion of the neural plate to the PPE. We therefore examined the effect of FGF2 along with BMP4 on the rostral neural plate explants and found that the explants became the simple squamous epithelia, which were characterized by the desmosomes/tonofilaments in membranes of adjacent cells. Such epithelia expressed sets of neural border markers and the PPE genes, suggesting that the neural plate explants were converted to a PPE-like tissue. This method will be useful for further studying mechanisms of PPE induction and subsequent specifications of the cranial placodes. PMID- 27369079 TI - Structural Features and Functional Dependency on beta-Clamp Define Distinct Subfamilies of Bacterial Mismatch Repair Endonuclease MutL. AB - In early reactions of DNA mismatch repair, MutS recognizes mismatched bases and activates MutL endonuclease to incise the error-containing strand of the duplex. DNA sliding clamp is responsible for directing the MutL-dependent nicking to the newly synthesized/error-containing strand. In Bacillus subtilis MutL, the beta clamp-interacting motif (beta motif) of the C-terminal domain (CTD) is essential for both in vitro direct interaction with beta-clamp and in vivo repair activity. A large cluster of negatively charged residues on the B. subtilis MutL CTD prevents nonspecific DNA binding until beta clamp interaction neutralizes the negative charge. We found that there are some bacterial phyla whose MutL endonucleases lack the beta motif. For example, the region corresponding to the beta motif is completely missing in Aquifex aeolicus MutL, and critical amino acid residues in the beta motif are not conserved in Thermus thermophilus MutL. We then revealed the 1.35 A-resolution crystal structure of A. aeolicus MutL CTD, which lacks the beta motif but retains the metal-binding site for the endonuclease activity. Importantly, there was no negatively charged cluster on its surface. It was confirmed that CTDs of beta motif-lacking MutLs, A. aeolicus MutL and T. thermophilus MutL, efficiently incise DNA even in the absence of beta clamp and that beta-clamp shows no detectable enhancing effect on their activity. In contrast, CTD of Streptococcus mutans, a beta motif-containing MutL, required beta-clamp for the digestion of DNA. We propose that MutL endonucleases are divided into three subfamilies on the basis of their structural features and dependence on beta-clamp. PMID- 27369080 TI - Site-specific Disruption of the Oct4/Sox2 Protein Interaction Reveals Coordinated Mesendodermal Differentiation and the Epithelial-Mesenchymal Transition. AB - Although the Oct4/Sox2 complex is crucial for maintaining the pluripotency of stem cells, the molecular basis underlying its regulation during lineage-specific differentiation remains unknown. Here, we revealed that the highly conserved Oct4/Lys-156 is important for maintaining the stability of the Oct4 protein and the intermolecular salt bridge between Oct4/Lys-151 and Sox2/Asp-107 that contributes to the Oct4/Sox2 interaction. Post-translational modifications at Lys 156 and K156N, a somatic mutation detected in bladder cancer patients, both impaired the Lys-151-Asp-107 salt bridge and the Oct4/Sox2 interaction. When produced as a recombinant protein or overexpressed in pluripotent stem cells, Oct4/K156N, with reduced binding to Sox2, significantly down-regulated the stemness genes that are cooperatively controlled by the Oct4/Sox2 complex and specifically up-regulated the mesendodermal genes and the SNAIL family genes that promote the epithelial-mesenchymal transition. Thus, we conclude that Oct4/Lys 156-modulated Oct4/Sox2 interaction coordinately controls the epithelial mesenchymal transition and mesendoderm specification induced by specific differentiation signals. PMID- 27369081 TI - Evidence That G-quadruplex DNA Accumulates in the Cytoplasm and Participates in Stress Granule Assembly in Response to Oxidative Stress. AB - Cells engage numerous signaling pathways in response to oxidative stress that together repair macromolecular damage or direct the cell toward apoptosis. As a result of DNA damage, mitochondrial DNA or nuclear DNA has been shown to enter the cytoplasm where it binds to "DNA sensors," which in turn initiate signaling cascades. Here we report data that support a novel signaling pathway in response to oxidative stress mediated by specific guanine-rich sequences that can fold into G-quadruplex DNA (G4DNA). In response to oxidative stress, we demonstrate that sequences capable of forming G4DNA appear at increasing levels in the cytoplasm and participate in assembly of stress granules. Identified proteins that bind to endogenous G4DNA in the cytoplasm are known to modulate mRNA translation and participate in stress granule formation. Consistent with these findings, stress granule formation is known to regulate mRNA translation during oxidative stress. We propose a signaling pathway whereby cells can rapidly respond to DNA damage caused by oxidative stress. Guanine-rich sequences that are excised from damaged genomic DNA are proposed to enter the cytoplasm where they can regulate translation through stress granule formation. This newly proposed role for G4DNA provides an additional molecular explanation for why such sequences are prevalent in the human genome. PMID- 27369083 TI - Inhibition of HDAC6 Protein Enhances Bortezomib-induced Apoptosis in Head and Neck Squamous Cell Carcinoma (HNSCC) by Reducing Autophagy. AB - Chemoresistance is a major barrier to effective chemotherapy of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Recently, autophagy, a highly conservative intracellular recycling system, has shown to be associated with chemoresistance in cancer cells. However, little is known about how autophagy plays a role in the development of chemoresistance in HNSCC and how autophagy is initiated when HNSCC cells undergo cytotoxic stress. Here, we report that autophagy was activated when HNSCC cells are treated with the proteasome inhibitor bortezomib, proposed as an alternative chemotherapeutic agent for both primary and cisplatin-resistant HNSCC cells. Ablation of histone deacetylase 6 (HDAC6) expression and its activity in HNSCC cells significantly inhibited autophagy induction by altering the phosphorylation status of mammalian target of rapamycin and enhanced the bortezomib cytotoxicity. Similarly, a combination regimen of bortezomib and the histone deacetylase inhibitor trichostatin A abolished HDAC6 activity and decreased autophagy induction while significantly enhancing bortezomib-induced apoptosis in HNSCC cells. These data uncover a novel molecular mechanism indicating that HDAC6 may serve as a critical causal link between autophagy, apoptosis, and the cell survival response in HNSCC. A combination regimen resulting in regression of autophagy improves chemotherapeutic efficacy, thereby providing a new strategy to overcome chemoresistance and to improve the treatment and survival of HNSCC patients. PMID- 27369082 TI - Biphasic Regulation of Yes-associated Protein (YAP) Cellular Localization, Phosphorylation, and Activity by G Protein-coupled Receptor Agonists in Intestinal Epithelial Cells: A NOVEL ROLE FOR PROTEIN KINASE D (PKD). AB - We examined the regulation of Yes-associated protein (YAP) localization, phosphorylation, and transcriptional activity in intestinal epithelial cells. Our results show that stimulation of intestinal epithelial IEC-18 cells with the G protein-coupled receptor (GPCR) agonist angiotensin II, a potent mitogen for these cells, induced rapid translocation of YAP from the nucleus to the cytoplasm (within 15 min) and a concomitant increase in YAP phosphorylation at Ser(127) and Ser(397) Angiotensin II elicited YAP phosphorylation and cytoplasmic accumulation in a dose-dependent manner (ED50 = 0.3 nm). Similar YAP responses were provoked by stimulation with vasopressin or serum. Treatment of the cells with the protein kinase D (PKD) family inhibitors CRT0066101 and kb NB 142-70 prevented the increase in YAP phosphorylation on Ser(127) and Ser(397) via Lats2, YAP cytoplasmic accumulation, and increase in the mRNA levels of YAP/TEAD-regulated genes (Ctgf and Areg). Furthermore, siRNA-mediated knockdown of PKD1, PKD2, and PKD3 markedly attenuated YAP nuclear-cytoplasmic shuttling, phosphorylation at Ser(127), and induction of Ctgf and Areg expression in response to GPCR activation. These results identify a novel role for the PKD family in the control of biphasic localization, phosphorylation, and transcriptional activity of YAP in intestinal epithelial cells. In turn, YAP and TAZ are necessary for the stimulation of the proliferative response of intestinal epithelial cells to GPCR agonists that act via PKD. The discovery of interaction between YAP and PKD pathways identifies a novel cross-talk in signal transduction and demonstrates, for the first time, that the PKDs feed into the YAP pathway. PMID- 27369084 TI - Changing Cycle Lengths in State-Transition Models: Challenges and Solutions. AB - The choice of a cycle length in state-transition models should be determined by the frequency of clinical events and interventions. Sometimes there is need to decrease the cycle length of an existing state-transition model to reduce error in outcomes resulting from discretization of the underlying continuous-time phenomena or to increase the cycle length to gain computational efficiency. Cycle length conversion is also frequently required if a new state-transition model is built using observational data that have a different measurement interval than the model's cycle length. We show that a commonly used method of converting transition probabilities to different cycle lengths is incorrect and can provide imprecise estimates of model outcomes. We present an accurate approach that is based on finding the root of a transition probability matrix using eigendecomposition. We present underlying mathematical challenges of converting cycle length in state-transition models and provide numerical approximation methods when the eigendecomposition method fails. Several examples and analytical proofs show that our approach is more general and leads to more accurate estimates of model outcomes than the commonly used approach. MATLAB codes and a user-friendly online toolkit are made available for the implementation of the proposed methods. PMID- 27369085 TI - Acquisition of the yeast Kluyveromyces marxianus from unpasteurised milk by a kefir grain enhances kefir quality. AB - Kefir is a fermented milk beverage consumed for nutritional and health tonic benefits in many parts of the world. It is produced by the fermentation of milk with a consortium of bacteria and yeast embedded within a polysaccharide matrix. This consortium is not well defined and can vary substantially between kefir grains. There are little data on the microbial stability of kefir grains, nor on interactions between microbes in the grain and in the milk. To study this, a grain was split, with one half of each stored at -20 degrees C and the other half passaged repeatedly in whole unpasteurised milk. Grains passaged in the unpasteurised milk recovered vigour and acquired the yeast Kluyveromyces marxainus from the milk which was confirmed to be the same strain by molecular typing. Furthermore, these passaged grains produced kefir that was distinguished chemically and organoleptically from the stored grains. Some changes in ultrastructure were also observed by scanning electron microscopy. The study showed that kefir grains can acquire yeast from their environment and the final product can be influenced by these newly acquired yeasts. Kluyveromyces marxianus is considered to be responsible for some of the most important characteristics of kefir so the finding that this yeast is part of the less stable microbiota is significant. PMID- 27369086 TI - Identification of active aerobic methanotrophs in plateau wetlands using DNA stable isotope probing. AB - Sedge-dominated wetlands on the Qinghai-Tibetan Plateau are methane emission centers. Methanotrophs at these sites play a role in reducing methane emissions, but relatively little is known about the composition of active methanotrophs in these wetlands. Here, we used DNA stable isotope probing to identify the key active aerobic methanotrophs in three sedge-dominated wetlands on the plateau. We found that Methylocystis species were active in two peatlands, Hongyuan and Dangxiong. Methylobacter species were found to be active only in Dangxiong peat. Hongyuan peat had the highest methane oxidation rate, and cross-feeding of carbon from methanotrophs to methylotrophic Hyphomicrobium species was observed. Owing to a low methane oxidation rate during the incubation, the labeling of methanotrophs in Maduo wetland samples was not detected. Our results indicate that there are large differences in the activity of methanotrophs in the wetlands of this region. PMID- 27369088 TI - Management of post-haemorrhagic hydrocephalus in premature infants. AB - Post-haemorrhagic hydrocephalus (PHH) is the most common neurological complication of preterm birth and can result in severe and life-long psychomotor and cognitive sequelae. Cerebrospinal fluid diversion is often required but the optimum time for intervention is unclear. Numerous neurosurgical procedures exist to temporise PHH but it is not clear which is the optimum method. Approximately 15% of preterm infants who suffer intraventricular haemorrhage (IVH) will require permanent cerebrospinal fluid diversion with a ventriculoperitoneal shunt. It is likely that earlier intervention may result in reduced neurological disability and ventriculoperitoneal shunt dependency. In this review we discuss the current methods of PHH management. PMID- 27369087 TI - Rathke's cleft cyst: A case report of recurrence and spontaneous involution. AB - Rathke's cleft cysts (RCC) are sellar lesions that typically remain asymptomatic throughout life. Symptomatic patients present with headache, visual disturbance and/or pituitary dysfunction and are treated with resection. We present a 61-year old woman diagnosed with RCC which was resected twice then recurred before undergoing spontaneous resolution. RCC are often managed without surgical intervention. Some of these lesions may spontaneously resolve without surgical intervention while others may become symptomatic. In patients with asymptomatic recurrent RCC conservative management is recommended. Spontaneous involution may occur following initial resection and recurrence of RCC. PMID- 27369089 TI - (210)Po in drinking water, its potential health effects, and inadequacy of the gross alpha activity MCL. AB - Polonium-210 ((210)Po) is a naturally-occurring, carcinogenic member of the (238)U decay series and the granddaughter of (210)Pb. It has a half life of 138.4days and is rarely found in drinking water at levels exceeding 5mBq/L because it strongly binds to aquifer sediment. When the current US Maximum Contaminant Level (MCL) covering (210)Po was promulgated in December 2000, very little was known about its occurrence and the processes responsible for mobilizing it. More is now known about the processes that mobilize (210)Po from sediments and a review of recent occurrence data show that it may not be as rare in the US as the US Environmental Protection Agency (USEPA) thought in 2000. Worldwide, only about 2200 analyses for (210)Po in drinking water were identified, with activities exceeding 500mBq/L being found only in Finland, India, Sweden, and the US. The median of 400 (210)Po analyses from the US is 4.75mBq/L and >10% of the samples exceed 500mBq/L. Current compliance-monitoring regulations in the US essentially guarantee that (210)Po contamination will not be detected except in very contaminated wells. Major problems with the US Gross Alpha Activity MCL include the volatility of (210)Po and extended holding times and sample-compositing methods that can allow the majority of (210)Po in a sample bottle to decay before analysis. In light of new information, the radionuclide rule should be changed and direct measurements of (210)Po should be made in all public-water supply wells to rule out its presence. Much of the important biological and toxicological research on (210)Po is more than four decades old and new laboratory research using modern tools is needed. Biological and epidemiological investigations of known contaminated areas are needed to assess the effect (210)Po exposure is having on animals and humans consuming the water. PMID- 27369090 TI - Wetland loss due to land use change in the Lower Parana River Delta, Argentina. AB - Wetland loss is a global concern because wetlands are highly diverse ecosystems that provide important goods and services, thus threatening both biodiversity and human well-being. The Parana River Delta is one of the largest and most important wetland ecosystems of South America, undergoing expanding cattle and forestry activities with widespread water control practices. To understand the patterns and drivers of land cover change in the Lower Parana River Delta, we quantified land cover changes and modeled associated factors. We developed land cover maps using Landsat images from 1999 and 2013 and identified main land cover changes. We quantified the influence of different socioeconomic (distance to roads, population centers and human activity centers), land management (area within polders, cattle density and years since last fire), biophysical variables (landscape unit, elevation, soil productivity, distance to rivers) and variables related to extreme system dynamics (flooding and fires) on freshwater marsh conversion with Boosted Regression Trees. We found that one third of the freshwater marshes of the Lower Delta (163,000ha) were replaced by pastures (70%) and forestry (18%) in only 14years. Ranching practices (represented by cattle density, area within polders and distance to roads) were the most important factors responsible for freshwater marsh conversion to pasture. These rapid and widespread losses of freshwater marshes have potentially large negative consequences for biodiversity and ecosystem services. A strategy for sustainable wetland management will benefit from careful analysis of dominant land uses and related management practices, to develop an urgently needed land use policy for the Lower Delta. PMID- 27369091 TI - Murine precision-cut lung slices exhibit acute responses following exposure to gasoline direct injection engine emissions. AB - Gasoline direct injection (GDI) engines are increasingly prevalent in the global vehicle fleet. Particulate matter emissions from GDI engines are elevated compared to conventional gasoline engines. The pulmonary effects of these higher particulate emissions are unclear. This study investigated the pulmonary responses induced by GDI engine exhaust using an ex vivo model. The physiochemical properties of GDI engine exhaust were assessed. Precision cut lung slices were prepared using Balb/c mice to evaluate the pulmonary response induced by one-hour exposure to engine-out exhaust from a laboratory GDI engine operated at conditions equivalent to vehicle highway cruise conditions. Lung slices were exposed at an air-liquid interface using an electrostatic aerosol in vitro exposure system. Particulate and gaseous exhaust was fractionated to contrast mRNA production related to polycyclic aromatic hydrocarbon (PAH) metabolism and oxidative stress. Exposure to GDI engine exhaust upregulated genes involved in PAH metabolism, including Cyp1a1 (2.71, SE=0.22), and Cyp1b1 (3.24, SE=0.12) compared to HEPA filtered air (p<0.05). GDI engine exhaust further increased Cyp1b1 expression compared to filtered GDI engine exhaust (i.e., gas fraction only), suggesting this response was associated with the particulate fraction. Exhaust particulate was dominated by high molecular weight PAHs. Hmox1, an oxidative stress marker, exhibited increased expression after exposure to GDI (1.63, SE=0.03) and filtered GDI (1.55, SE=0.04) engine exhaust compared to HEPA filtered air (p<0.05), likely attributable to a combination of the gas and particulate fractions. Exposure to GDI engine exhaust contributes to upregulation of genes related to the metabolism of PAHs and oxidative stress. PMID- 27369092 TI - Past and Present Post-Fire Environments. PMID- 27369093 TI - Identification of sources of tar balls deposited along the Southwest Caspian Coast, Iran using fingerprinting techniques. AB - In 2012, a significant number of tar balls occurred along the Southwest coasts of the Caspian Sea (Iran). Several oil fields of Turkmenistan, Azerbaijan and Iran might be sources of oil spills and lead to the formation of these tar balls. For source identification, 6 tar ball samples were collected from the Southwest beaches of the Caspian Sea and subjected to fingerprint analysis based on the distribution of the source-specific biomarkers of pentacyclic tri-terpanes and steranes. Comparing the diagenic ratios revealed that the tar balls were chemically similar and originated from the same source. Results of double ratio plots (e.g., C29/C30 versus ?C31-C35/C30 and C28 alphabetabeta/(C27 alphabetabeta+C29 alphabetabeta) versus C29 alphabetabeta/(C27 alphabetabeta+C28 alphabetabeta)) in the tar balls and oils from Iran, Turkmenistan and Azerbaijan indicated that the tar balls might be the result of spills from Turkmenistan oil. Moreover, principle component analysis (PCA) using biomarker ratios on the tar balls and 20 crude oil samples from different wells of Azerbaijan, Iran and Turkmenistan oils showed that the tar balls collected at the Southwest beaches are highly similar to the Turkmenistan oil but one of the Azerbaijan oils (from Bahar field oils) was found to be also slightly close to the tar balls. The weathering characterizations based on the presence of UCM (unresolved complex mixture) and low/high molecular weight ratios (L/H) of alkanes and PAHs indicated the tar ball samples have been significantly influenced by natural weathering processes such as evaporation, photo-degradation and biodegradation. This is the first study of its kind in Iran to use fingerprinting for source identification of tar balls. PMID- 27369094 TI - Parental Understanding of Hospital Course and Discharge Plan. AB - OBJECTIVES: Hospital discharge marks an important transition in care from the inpatient team to the family and primary care provider. Parents must know the hospital course and discharge plan to care for their child at home and provide background for future providers. Our study aimed to determine parental knowledge of key aspects of their child's hospital course and discharge plan and to identify markers of increased risk for incomplete or incorrect knowledge among participants. METHODS: We conducted a descriptive prospective cohort study of parents within 24 hours of hospital discharge. The primary outcome was concordance of parent responses to verbal interview questions about their child's hospital treatment, laboratory testing, imaging, procedures and discharge plan with the medical record. RESULTS: Of 174 participants, 15% felt less than "completely prepared" to explain the hospital course to their primary care provider or to provide care after discharge. There was >83% overall concordance with interview responses and the medical record, with concordance higher for hospital course events than discharge plan. There were few significant differences in understanding between trainee-based teams and the attending physician-run unit. No patient or family characteristics were consistently associated with poor understanding of hospital course or discharge plan. CONCLUSIONS: Although parents were generally knowledgeable about hospital course and discharge plan, areas for improved communication were identified. Individualized counseling about hospital course and discharge plan should be initiated for all parents early during hospitalization. Methods that assess and bolster caregiver comprehension and minimize dependence on written instructions may help with transition to outpatient care. PMID- 27369095 TI - The imitation game: Effects of social cues on 'imitation' are domain-general in nature. AB - Imitation has been hailed as 'social glue', facilitating rapport with others. Previous studies suggest that social cues modulate imitation but the mechanism of such modulation remains underspecified. Here we examine the locus, specificity, and neural basis of the social control of imitation. Social cues (group membership and eye gaze) were manipulated during an imitation task in which imitative and spatial compatibility could be measured independently. Participants were faster to perform compatible compared to incompatible movements in both spatial and imitative domains. However, only spatial compatibility was modulated by social cues: an interaction between group membership and eye gaze revealed more spatial compatibility for ingroup members with direct gaze and outgroup members with averted gaze. The fMRI data were consistent with this finding. Regions associated with the control of imitative responding (temporoparietal junction, inferior frontal gyrus) were more active during imitatively incompatible compared to imitatively compatible trials. However, this activity was not modulated by social cues. On the contrary, an interaction between group, gaze and spatial compatibility was found in the dorsolateral prefrontal cortex in a pattern consistent with reaction times. This region may be exerting control over the motor system to modulate response inhibition. PMID- 27369096 TI - Depth magnitude from stereopsis: Assessment techniques and the role of experience. AB - Investigations of the relationship between binocular disparity and suprathreshold depth magnitude percepts have used a variety of tasks, stimuli, and methods. Collectively, the results confirm that depth percepts increase with increasing disparity, but there are large differences in how well the estimates correspond to geometric predictions. To evaluate the source of these differences, we assessed depth magnitude percepts for simple stereoscopic stimuli, using both intra- and cross-modal estimation methods, and a large range of test disparities for both experienced and inexperienced observers. Our results confirm that there is a proportional relationship between perceived depth and binocular disparity; this relationship is not impacted by the measurement method. However, observers with minimal prior experience showed strong systematic biases in depth estimation, which resulted in large overestimates at small disparities and substantial underestimates at large disparities. By comparison, experienced observers' depth judgements were much closer to geometric predictions. In subsequent studies we show that unpracticed observers' depth estimates are improved by removing conflicting depth cues, and the observed biases are eliminated when they view physical targets. We conclude that differences in the depth magnitude estimates as a function of disparity in the existing literature are likely due to observers' experience with stereoscopic display systems in which binocular disparity is manipulated while other depth cues are held constant. PMID- 27369097 TI - The structure of inter-individual differences in visual ability: Evidence from the general population and synaesthesia. AB - This study considers how inter-individual differences in visual ability are structured. Visual ability could be a single entity (along the lines of general intelligence, or 'g'), or could be structured according to major anatomical or physiological pathways (dorsal v. ventral streams; magno- v. parvo-cellular systems); or may be a finer-grained mosaic of abilities. To test this, we employed seven visual psychophysical tests (generating 16 measures) on a large (100+) sample of neurotypical participants. A Varimax-rotated PCA (Principal Component Analysis) revealed a two-factor solution that broadly corresponds to a high and low spatial frequency division (consistent with a magno/parvo distinction). Over and above this, two measures (temporal order judgments; gain in contrast sensitivity) correlated with most others, and loaded on both factors, suggesting that they tap broad visual processing demands. These analyses open up further possibilities for exploring the genetic and neuroscientific foundations of differences in visual ability. The tests were also run on a group of individuals with different types of visually-based synaesthesia, given that previous research have suggested they possess a distinct profile of visual abilities. Synaesthesia was linked to enhanced processing of colour and shape/curvature information (amongst others), that may relate to differences in V4 in this group. In conclusion, individual differences in vision are both striking and meaningful, despite our difficulty to imagine seeing the world any differently. PMID- 27369099 TI - [Single-family rooms for neonatal intensive care units impacts on preterm newborns, families, and health-care staff. A systematic literature review]. AB - The quality of the environment is an essential point in the care of preterm newborns. The design of neonatal intensive care units (NICUs) (open-bay, single patient room, single-family room) directly affects both the preterm newborns and their caregivers (parents, healthcare staff). The aim of this systematic review was to evaluate the impact of single-family rooms on the preterm newborn, its parents, and the staff. Single-family rooms improve outcome for the preterm newborn, with increasing parental involvement and better control of the environment (fewer inappropriate stimulations such as high levels of noise and illumination). This kind of NICU design also improves parental and staff satisfaction. PMID- 27369098 TI - The relation between spatial perspective taking and inhibitory control in 6-year old children. AB - Developmental research on spatial perspective taking has shown that young children are able to solve perspective-taking problems under favorable circumstances, but they have difficulties succeeding in classic tasks involving a conflict between one's own perspective and that of another observer. To date, little is known about the reasons for young children's difficulties in dealing with incongruent perspectives. Based on the assumption that one's own perspective has to be ignored to imagine someone else's perspective, it was investigated whether perspective taking is related to inhibitory control in 6-year-olds (N = 140). An adapted version of the 'Fruit Stroop task', appropriate for preschool children, was used to assess inhibitory control. Perspective taking was assessed using the 'Perspective-Taking Test for Children'. Other spatial and nonspatial abilities were assessed to investigate the specificity of the relation. Results showed a significant correlation between perspective taking and inhibitory control, even when controlled for age, verbal-IQ, and socio-economic status. However, no significant correlations between inhibition and other spatial abilities were found, indicating a specific relation between inhibition and perspective taking. A linear regression analysis showed that, even after accounting for effects of control variables as well as other mental transformation abilities, inhibition accounted for a significant part of the variance in perspective-taking performance. The present findings provide valuable information on what contributes to individual differences in perspective taking, which is an important aspect of everyday cognition and bears relevance for reasoning in technical domains. PMID- 27369100 TI - [An unusual cause of seizure in a 9-year-old child]. PMID- 27369101 TI - [Evaluation of the measurement of capillary glucose concentration versus plasma glucose in the newborn]. AB - BACKGROUND: The reliability of blood glucose monitoring in neonatology is not always confirmed. The aim of this study was to evaluate the reliability of blood glucose measurements made with three different devices in newborns. PATIENTS AND METHODS: The study was prospective, conducted in a medical and neonatal intensive care department over a period of 4 months. Capillary glucose level was measured with three different glucometers and compared with venous glucose level determined using the hexokinase method. An ANOVA and Scheffe test were used for the correlation analysis. RESULTS: Three hundred and nine infants were included, with a mean age of 55h and a mean term of 39 weeks of gestation. Mean blood glucose in the laboratory was 0.62+/-0.15g/L, 0.71+/-0.17g/L for Accu-Chek((r)) Active, 0.80+/-0.17g/L for Accu-Chek((r)) Performa, and 0.83+/-0.12g/L for Bionime. An ANOVA showed statistically significant differences between the measurements made by glucometers compared to the reference blood glucose levels, and the Scheffe method showed that glucometers overestimated the real plasma glucose levels. CONCLUSION: None of the devices used in this study was satisfactory. However, an estimation of blood glucose taking into consideration this numerical overestimation would allow early detection of hypoglycemia. PMID- 27369102 TI - [Gordon syndrome: The importance of measuring blood pressure in children]. AB - Gordon's syndrome, or type II pseudo-hypoaldosteronism, is a rare cause of arterial hypertension in children. However, it is important to diagnose this syndrome because of the spectacular efficacy of thiazide diuretics. The typical clinical picture of Gordon syndrome includes, apart from arterial hypertension and dyskaliemia, hyperchloremia metabolic acidosis, hypercalciuria, a low rate of renin, and most frequently, a normal or high rate of aldosterone. Dental abnormalities and growth retardation can also be associated. In most cases, it is inherited in an autosomal dominant pattern. We report on a 7-year-old girl who was discovered with arterial hypertension during a consultation for chronic diarrhea. The association of growth retardation, hyperkaliemia, and metabolic acidosis oriented the diagnosis. Starting a thiazide diuretic helped control the arterial hypertension and the kaliemia in a spectacular manner. The genetic analysis proved the existence of a splice mutation on exon 9 of the CUL3 gene coding for cullin 3. This mutation is de novo. PMID- 27369103 TI - [Use of levosimendan in children]. AB - Levosimendan is a calcium-sensitizing drug with positive inotropic properties. As an inodilator, this molecule also has a vasodilation effect. While its efficacy has been demonstrated in the adult in the context of cardiac surgery, its pediatric use is still not widespread. Many studies have shown its safety of use in children, including in the newborn. Across the world, a growing number of teams use levosimendan to treat both acute and chronic heart failure. Through a review of the literature, we describe its pharmacodynamic effects, its current applications, and its perspectives of use in children. PMID- 27369104 TI - [Fat overload syndrome]. AB - We report the case of a 21-month-old child suffering from pulmonary fibrosis, who presented with acute respiratory distress and liver damage, due to an accidental overdose of intravenous lipid emulsion. This poisoning is a rare entity, whose potential severity and almost exclusive iatrogenic effect deserve to be remembered. PMID- 27369105 TI - Prospective evaluation of a cutaneous stimulation technique to induce on-demand urination in non-toilet-trained infants. AB - CONTEXT: When a urinary tract infection is suspected, it is recommended to capture a midstream sample of urine for analysis, but this strategy is difficult to apply before successful toilet training. A cutaneous stimulation technique has been reported to be effective in provoking micturition in newborns. OBJECTIVE: To evaluate the feasibility and the efficacy of this technique in a population of non-toilet-trained infants. DESIGN AND METHODS: Fifty infants were enrolled in this prospective non-controlled study in three pediatric emergency departments. The bladder was stimulated through suprapubic and paravertebral cutaneous stimulation as previously reported in newborns. The evaluation criterion was the proportion of patients from whom urine had been collected within the first 5min of the procedure. RESULTS: Forty-eight patients (21 boys) were evaluated. The procedure was successful in 27% of the cases overall, but reached 46% for children aged less than 3 months. Elevated weight was associated with failure of the procedure. CONCLUSION: Despite promising results in newborns, the cutaneous stimulation technique to provoke micturition appears to encounter limitations in older children. Nevertheless, the technique is an attractive alternative to urethral catheterization or suprapubic aspiration for infants younger than 3 months. PMID- 27369106 TI - [Purulent corneal melting: An unexpected complication of acute otitis media]. PMID- 27369107 TI - [A rare cause of epilepsy: Lipoma of the sylvian fissure]. PMID- 27369108 TI - The Use of Nucleosome Substrates Improves Binding of SAM Analogs to SETD8. AB - SETD8 is the methyltransferase responsible for monomethylation of lysine at position 20 of the N-terminus of histone H4 (H4K20). This activity has been implicated in both DNA damage and cell cycle progression. Existing biochemical assays have utilized truncated enzymes containing the SET domain of SETD8 and peptide substrates. In this report, we present the development of a mechanistically balanced biochemical assay using full-length SETD8 and a recombinant nucleosome substrate. This improves the binding of SAM, SAH, and sinefungin by up to 10,000-fold. A small collection of inhibitors structurally related to SAM were screened and 40 compounds were identified that only inhibit SETD8 when a nucleosome substrate is used. PMID- 27369110 TI - Practical Epidemiology. PMID- 27369109 TI - L'Echinococcose Pulmonaire Et Hepatique. AB - Report of two cases of echinococcosis of lung and liver and review of the literature. PMID- 27369111 TI - Differential Response to Anti-VEGF Regimens in Age-Related Macular Degeneration Patients with Early Persistent Retinal Fluid. AB - PURPOSE: To compare the effect of intravitreal aflibercept or ranibizumab drug type and frequency on visual acuity outcomes in eyes with neovascular age-related macular degeneration (NVAMD) and early persistent retinal fluid after 3 initial monthly injections. DESIGN: A post hoc analysis of eyes enrolled in VIEW 1 and VIEW 2, 2 similarly designed, randomized, phase 3 trials. PARTICIPANTS: A total of 1815 eyes with NVAMD from VIEW 1 and VIEW 2. METHODS: Analyses included patients with known fluid status at baseline and weeks 4, 8, and 12 in 3 treatment groups: ranibizumab 0.5 mg every 4 weeks (Rq4) (n = 595), intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4) (n = 613), and IAI 2 mg every 8 weeks (2q8) after 3 monthly injections (n = 607). MAIN OUTCOME MEASURES: Mean best-corrected visual acuity (BCVA) change from baseline over weeks 16 to 52 and the proportion of eyes that gained >=15 letters or lost >=5 letters were evaluated in eyes with and without persistent fluid (cystic intraretinal or subretinal fluid at all 4 initial visits). Visual outcomes also were assessed in eyes with persistent fluid by fluid type (intraretinal and subretinal fluid). RESULTS: The proportions of eyes with persistent fluid were 29.4%, 18.8%, and 20.3% in the Rq4, 2q4, and 2q8 groups, respectively. In these eyes, mean BCVA gain from baseline to week 52 was greater with 2q4 compared with Rq4 (P < 0.01) and 2q8 (P < 0.05), whereas it was similar with Rq4 and 2q8 (P = 0.294). At week 52, similar proportions of eyes gained >=15 letters (31.5%-35.2%), whereas fewer eyes lost >=5 letters with 2q4 compared with Rq4 and 2q8 (6.5% vs. 16.6% and 16.2%). The pattern of visual outcomes was similar regardless of fluid type. In eyes without persistent fluid, BCVA changes were similar across treatment groups. CONCLUSIONS: In patients with early persistent fluid, 2q4 may provide additional clinical benefit over 2q8 or Rq4. PMID- 27369112 TI - Cofilin is correlated with sperm quality and influences sperm fertilizing capacity in humans. AB - Spermatozoa should undergo a series of biochemical modifications in female reproduction tract, which is collectively called sperm capacitation. The capacitated spermatozoa can bind to the egg zona pellucida, resulting in the occurrence of acrosome reaction which enabled spermatozoa penetrate into the egg. The formation of actin plays an important role in these processes. Actin polymerized during sperm capacitation, but the polymers dispersed before acrosome reaction. In this study, we take our focus on actin-binding protein, cofilin. Our results showed that the % and intensity of sperm expressing cofilin in normal sperm were significantly higher than in abnormal sperm, and the sperm expressing cofilin was correlated with sperm quality. Furthermore, treatment with anti cofilin antibody increased the percentage of sperm capacitation and inhibited progesterone- or A23187- induced acrosome reaction in a dose-dependent manner. The presence of 100 ng/mL anti-cofilin antibodies markedly blocked the sperm penetration of zona-free hamster eggs. Besides, immunofluorescence results revealed that cofilin was colocalized with F-actin in the midpiece of spermatozoa; however, phospho-cofilin was expressed in the tail rather than in the midpiece of spermatozoa, which was not colocalized with F-actin in spermatozoa. Moreover, western blot revealed that phospho-cofilin increased in sperm capacitation, and the total cofilin and cofilin in insoluble fraction increased in acrosome reaction; immunofluorescence results showed that the amount of cofilin in acrosome increased in sperm capacitation. In conclusion, our study revealed that cofilin expression in human sperm is correlated with sperm quality and the alterations of cofilin and phospho-cofilin in fertilization affects sperm capacitation, acrosome reaction, and spermatozoa-oocyte fusion. PMID- 27369113 TI - Corrigendum to: "Burkholderia novacaledonica sp. nov. and B. ultramafica sp. nov. isolated from roots of Costularia spp. pioneer plants of ultramafic soils in New Caledonia" [Syst. Appl. Microbiol. 39 (2016) 151-159]. PMID- 27369114 TI - Double sellar floor sign: a clue of pituitary tumor. PMID- 27369115 TI - Additive effects of low concentrations of estradiol-17beta and progesterone on nitric oxide production by human vascular endothelial cells through shared signaling pathways. AB - Potential cardiovascular benefits of low-dose formulations of estrogens and progesterone (P4) for treating climacteric symptoms in postmenopausal women remain unclear because information is lacking on their combined vascular effects. Protective effects of low concentrations (5nM) of P4 and estradiol-17beta (E2), alone and in combination (P4+E2), were investigated in a nongenomic model of vascular protection which measured acute increases in nitric oxide (NO) production by cultured human umbilical vein endothelial cells (HUVECs). Treatment with 5nM P4+E2 for twenty minutes significantly increased NO production and endothelial NO synthase (eNOS) phosphorylation, whereas 5nM treatments with either steroid alone were ineffective. The 5nM P4+E2 treatment also increased phosphorylation of ERK and Akt, mimicking the effects of higher concentrations of P4 and E2 alone. Pre-treatment with inhibitors of PI3K (wortmannin), Akt (ML-9), and MAP kinase (AZD6244 and U0126) completely blocked the NO response to 5nM P4+E2. Combined 5nM treatments with specific estrogen and progesterone receptor agonists showed an involvement of membrane progesterone receptor alpha (mPRalpha, also known as PAQR7), G protein-coupled estrogen receptor 1 (GPER), and estrogen receptor alpha (ERalpha), but not ERbeta, in P4+E2 stimulation of NO production. P4+E2 also exerted genomic actions, increasing mPRalpha, GPER, cyclooxygenase-1, and prostacyclin-synthase mRNA levels. Taken together, the results show that a low concentration of P4+E2 rapidly increases NO production in HUVECs through mPRalpha, ERalpha, and GPER and involves common signaling pathways, PI3K/Akt and MAP kinase. These in vitro findings suggest that low doses of E2 and P4 may also have some beneficial cardiovascular effects in vivo when administered as hormone replacement therapy (HRT) for post-menopausal women. PMID- 27369117 TI - Cardioplegia: solutions or strategies? PMID- 27369118 TI - Surgical results for pulmonary atresia with intact ventricular septum: a single centre 15-year experience and medium-term follow-up. AB - OBJECTIVES: The optimal surgical strategies for pulmonary atresia with intact ventricular septum (PAIVS) are still not well established. This study reviewed our 15-year experience in the management of PAIVS. METHODS: Between July 1999 and June 2014, 170 patients were treated for PAIVS in our heart centre. Based on the morphology of the right ventricle (RV), age and surgical approaches, the patients were divided into two groups: the one-stage surgery group (n = 33) and the staged surgery group (n = 137), in which patients received definitive repair, including biventricular repair, 1.5 ventricular repair and univentricular palliation without or with initial intervention. The median follow-up time was 6.6 years (range: 1-15 years); survival rates, risk factors for death and clinical status after operation were assessed. RESULTS: In the one-stage surgery group, there were three deaths post operation; the estimated 1-, 5- and 15-year survival rates were 97.0, 93.7 and 88.5%, respectively. In the staged surgery group, 23 patients died, including 15 in the waiting period after initial intervention. The estimated 1-, 5- and 15-year survival rates of the staged group were 89.8, 88.2 and 69.1%, without significant difference when compared with the one-stage surgery group (P > 0.05). Independent predictors of mortality were severe RV hypoplasia (P < 0.05) and lower tricuspid valve Z-scores (P < 0.01). At the latest follow-up, most of the patients in both groups had a good clinical status after definitive repair. The re-operation rate was 16.0% (4/25) in the one-stage surgery group compared with 15.4% (6/39) in the staged surgery group. CONCLUSIONS: Both one-stage repair and the staged surgical procedure had acceptable surgical outcomes in this retrospective study. Initial intervention is suitable for neonates or younger patients to promote the growth of the RV, and one-stage definitive repair is a beneficial choice for older patients with PAIVS, in whom the growth potential of the RV is limited. PMID- 27369119 TI - Determining the value of pulmonary metastasectomy. PMID- 27369120 TI - Analysis of pulmonary metastasis as an indication for operation: an evidence based approach. PMID- 27369121 TI - A view of the Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) trial from the coalface. PMID- 27369122 TI - How to Restore Fairness After Doping Infringement? AB - This article addresses the question how to restore the biggest possible amount of fairness after a discovery of doping infringement. I will analyse eight actions that could be taken: (1) disqualification and re-ranking, (2) change in official result, (3) medal stripping and medal re-awarding, (4) ban, (5) rematch, (6) legal action, (7) apology and (8) forgiveness. I conclude that the best way to restore the biggest possible amount of fairness seems to be a selected combination of actions. I also propose that re-ranking and medal re-awarding should be accompanied by a ceremony in which the new winners are celebrated because they typically did not have the possibility of enjoying their success in front of the original audience. PMID- 27369123 TI - Outcome measures based on classification performance fail to predict the intelligibility of binary-masked speech. AB - To date, the most commonly used outcome measure for assessing ideal binary mask estimation algorithms is based on the difference between the hit rate and the false alarm rate (H-FA). Recently, the error distribution has been shown to substantially affect intelligibility. However, H-FA treats each mask unit independently and does not take into account how errors are distributed. Alternatively, algorithms can be evaluated with the short-time objective intelligibility (STOI) metric using the reconstructed speech. This study investigates the ability of H-FA and STOI to predict intelligibility for binary masked speech using masks with different error distributions. The results demonstrate the inability of H-FA to predict the behavioral intelligibility and also illustrate the limitations of STOI. Since every estimation algorithm will make errors that are distributed in different ways, performance evaluations should not be made solely on the basis of these metrics. PMID- 27369125 TI - Erratum: Relative sound localisation abilities in human listeners [J. Acoust. Soc. Am. 138, 674-686 (2015)]. PMID- 27369126 TI - Scattering of guided waves at delaminations in composite plates. AB - Carbon fiber laminate composites are increasingly employed for aerospace structures as they offer advantages, such as a good strength to weight ratio. However, impact during the operation and servicing of the aircraft can lead to barely visible and difficult to detect damage. Depending on the severity of the impact, fiber and matrix breakage or delaminations can occur, reducing the load carrying capacity of the structure. Efficient nondestructive testing and structural health monitoring of composite panels can be achieved using guided ultrasonic waves propagating along the structure. The scattering of the A0 Lamb wave mode at delaminations was investigated using a full three-dimensional (3D) finite element (FE) analysis. The influence of the delamination geometry (size and depth) was systematically evaluated. In addition to the depth dependency, a significant influence of the delamination width due to sideways reflection of the guided waves within the delamination area was found. Mixed-mode defects were simulated using a combined model of delamination with localized material degradation. The guided wave scattering at cross-ply composite plates with impact damage was measured experimentally using a non-contact laser interferometer. Good agreement between experiments and FE predictions using the mixed-mode model for an approximation of the impact damage was found. PMID- 27369127 TI - Time reversal for localization of sources of infrasound signals in a windy stratified atmosphere. AB - Time reversal is used for localizing sources of recorded infrasound signals propagating in a windy, stratified atmosphere. Due to the convective effect of the background flow, the back-azimuths of the recorded signals can be substantially different from the source back-azimuth, posing a significant difficulty in source localization. The back-propagated signals are characterized by negative group velocities from which the source back-azimuth and source-to receiver (STR) distance can be estimated using the apparent back-azimuths and trace velocities of the signals. The method is applied to several distinct infrasound arrivals recorded by two arrays in the Netherlands. The infrasound signals were generated by the Buncefield oil depot explosion in the U.K. in December 2005. Analyses show that the method can be used to substantially enhance estimates of the source back-azimuth and the STR distance. In one of the arrays, for instance, the deviations between the measured back-azimuths of the signals and the known source back-azimuth are quite large (-1 degrees to -7 degrees ), whereas the deviations between the predicted and known source back-azimuths are small with an absolute mean value of <1 degrees . Furthermore, the predicted STR distance is off only by <5% of the known STR distance. PMID- 27369128 TI - A study of ribbing effect on the vibration response and transmission of an L shaped plate. AB - This paper presents an analytical solution for the vibration response of a ribbed L-shaped plate using a modal expansion solution approach. The analytical model is then employed to study the ribbing effect on vibration reduction and transmission between the two plate components of the L-shaped plate. It is found that for the system considered in the study, a rib inserted between the excitation force and the source plate can lead to a large vibration reduction for both source and receiving plates except at a frequency band near the fundamental resonant frequency of the rib where the rib's flexural stiffness is negligible. A reduced vibration transmission to the receiving plate can also be achieved by placing a rib near the plate/plate junction, attributed to the increased moment impedance at the coupling after the rib insertion. Increasing the rib's flexural stiffness under this condition can further reduce vibration transmission in the low frequency bands while increasing the rib's mass can lead to a reduced vibration transmission in the higher frequency bands. The insights obtained from this study are relevant to vibration control of structures such as transformer tanks and machine covers. PMID- 27369129 TI - How the demographic makeup of our community influences speech perception. AB - Speech perception is known to be influenced by listeners' expectations of the speaker. This paper tests whether the demographic makeup of individuals' communities can influence their perception of foreign sounds by influencing their expectations of the language. Using online experiments with participants from all across the U.S. and matched census data on the proportion of Spanish and other foreign language speakers in participants' communities, this paper shows that the demographic makeup of individuals' communities influences their expectations of foreign languages to have an alveolar trill versus a tap (Experiment 1), as well as their consequent perception of these sounds (Experiment 2). Thus, the paper shows that while individuals' expectations of foreign language to have a trill occasionally lead them to misperceive a tap in a foreign language as a trill, a higher proportion of non-trill language speakers in one's community decreases this likelihood. These results show that individuals' environment can influence their perception by shaping their linguistic expectations. PMID- 27369130 TI - Comparing the effects of age on amplitude modulation and frequency modulation detection. AB - Frequency modulation (FM) and amplitude modulation (AM) detection thresholds were measured at 40 dB sensation level for young (22-28 yrs) and older (44-66 yrs) listeners with normal audiograms for a carrier frequency of 500 Hz and modulation rates of 2 and 20 Hz. The number of modulation cycles, N, varied between 2 and 9. For FM detection, uninformative AM at the same rate as the FM was superimposed to disrupt excitation-pattern cues. For both groups, AM and FM detection thresholds were lower for the 2-Hz than for the 20-Hz rate, and AM and FM detection thresholds decreased with increasing N. Thresholds were higher for older than for younger listeners, especially for FM detection at 2 Hz, possibly reflecting the effect of age on the use of temporal-fine-structure cues for 2-Hz FM detection. The effect of increasing N was similar across groups for both AM and FM. However, at 20 Hz, older listeners showed a greater effect of increasing N than younger listeners for both AM and FM. The results suggest that ageing reduces sensitivity to both excitation-pattern and temporal-fine-structure cues for modulation detection, but more so for the latter, while sparing temporal integration of these cues at low modulation rates. PMID- 27369131 TI - Auditory sensitivity in aquatic animals. AB - A critical concern with respect to marine animal acoustics is the issue of hearing "sensitivity," as it is widely used as a criterion for the onset of noise induced effects. Important aspects of research on sensitivity to sound by marine animals include: uncertainties regarding how well these species detect and respond to different sounds; the masking effects of man-made sounds on the detection of biologically important sounds; the question how internal state, motivation, context, and previous experience affect their behavioral responses; and the long-term and cumulative effects of sound exposure. If we are to better understand the sensitivity of marine animals to sound we must concentrate research on these questions. In order to assess population level and ecological community impacts new approaches can possibly be adopted from other disciplines and applied to marine fauna. PMID- 27369133 TI - Optimal design of a hysteretic vibration absorber using fixed-points theory. AB - Hinfinity optimum parameters of a dynamic vibration absorber (DVA) using a hysteretic or structural damping element have been derived analytically for suppressing vibration of a single degree-of-freedom (SDOF) system excited by harmonic forces or due to ground motions. Although the frequency response function of the traditional DVA (TDVA) with viscous damping may be converted to that of the hysteretic DVA (HDVA) using the equivalent viscous damping coefficient, it is found that the two frequency response functions are not equivalent after the optimization process. Therefore, the optimum parameters of the HDVA are derived using the fixed-points theory rather than converted directly from the TDVA model. The analytical results show that the optimized hysteretic vibration absorber can provide a similar vibration reduction effect as the optimized traditional dynamic vibration absorber at the resonance of a SDOF primary vibrating system. Advantages as well as the limitations of the fixed points theory for the Hinfinity optimization of the hysteretic dynamic vibration absorbers using the fixed-points theory are discussed. PMID- 27369132 TI - The influence of native-language tones on lexical access in the second language. AB - When listening to speech in a second language, bilinguals' perception of acoustic phonetic properties is often influenced by the features that are important in the native language of the bilingual. Furthermore, changes in the perception of segmental contrasts due to L1 experience can influence L2 lexical access during comprehension. The present study investigates whether the effect of L1 experience on L2 processing seen at the segmental level extends to suprasegmental processing. In an eye-tracking task, Mandarin-English bilinguals heard an auditorily presented English word and selected which of two visually presented Chinese characters represented the correct Mandarin translation. The pitch contour of the spoken word was manipulated to either match or mismatch the lexical tone of the Mandarin translation. Results revealed that bilinguals were significantly faster to correctly identify the target and made earlier eye movements to targets when the suprasegmental information of the word spoken in English matched that of its Mandarin translation. The findings provide compelling evidence for bilinguals' sensitivity to suprasegmental tone information, even when listening to a non-tonal language. These results have important implications for the effect of L1 experience on L2 lexical access and language interaction in bilinguals, and are consistent with a highly interactive account of language processing. PMID- 27369134 TI - Effect of acoustic fine structure cues on the recognition of auditory-only and audiovisual speech. AB - This study addressed the hypothesis that an improvement in speech recognition due to combined envelope and fine structure cues is greater in the audiovisual than the auditory modality. Normal hearing listeners were presented with envelope vocoded speech in combination with low-pass filtered speech. The benefit of adding acoustic low-frequency fine structure to acoustic envelope cues was significantly greater for audiovisual than for auditory-only speech. It is suggested that this is due to complementary information of the different acoustic and visual cues. The results have potential implications for the assessment of bimodal cochlear implant fittings or electroacoustic stimulation. PMID- 27369135 TI - Erratum: A parametric analysis of waves propagating in a porous solid saturated by a three-phase fluid [J. Acoust. Soc. Am. 138(5), 3033-3042 (2015)]. PMID- 27369136 TI - Adaptive whitening of ambient ocean noise with narrowband signal preservation. AB - Passive underwater listening devices are often deployed to listen for narrowband signals of interest in time-varying background ocean noise. Such tonals are generated mechanically by ships, submarines, and machines, or acoustically by aquatic wildlife. Quantization of the sensor data for storage or low bit-rate transmission adds white noise which can overwhelm weak narrowband signals if the background noise is sufficiently colored. Whitening the background noise prior to quantization can reduce the detrimental effects, but the whitening process must preserve any tonals in the signal for maximum effectiveness. Existing adaptive whitening techniques make no effort to avoid suppressing tonals in the whitening process, while existing spectral separation methods fail to whiten background noise. The proposed methods perform adaptive whitening of background ambient noise while preserving narrowband tones at their original signal-to-noise ratios. The proposed methods are shown to outperform combinations of existing partial solutions both subjectively and by evaluating the objective criteria introduced. The stability and convergence properties of the proposed algorithms match or surpass those of existing well-known adaptive algorithms. PMID- 27369137 TI - Analysis and modeling of infrasound from a four-stage rocket launch. AB - Infrasound from a four-stage sounding rocket was recorded by several arrays within 100 km of the launch pad. Propagation modeling methods have been applied to the known trajectory to predict infrasonic signals at the ground in order to identify what information might be obtained from such observations. There is good agreement between modeled and observed back azimuths, and predicted arrival times for motor ignition signals match those observed. The signal due to the high altitude stage ignition is found to be low amplitude, despite predictions of weak attenuation. This lack of signal is possibly due to inefficient aeroacoustic coupling in the rarefied upper atmosphere. PMID- 27369138 TI - Unphysical consequences of negative absorbed power in linear passive scattering: Implications for radiation force and torque. AB - Contrary to some claims, the absorbed power associated with linear scattering of sound by passive objects in ideal fluids must be non-negative. Such unphysical claims suggest analytical or computational error, or use of an unphysical constitutive relation for material properties. The close connection with the evaluation of acoustic radiation force on targets according to Westervelt's formulation [J. Acoust. Soc. Am. 29, 26-29 (1957)], recently generalized to certain acoustic beams, is briefly reviewed along with the theory of acoustic radiation torque on axisymmetric targets with power absorption. Applications to viscous dissipation and to issues pertaining to active targets are also examined. PMID- 27369139 TI - A two-dimensional analysis of the sensitivity of a pulse first break to wave speed contrast on a scale below the resolution length of ray tomography. AB - Mapping the speed of mechanical waves traveling inside a medium is a topic of great interest across many fields from geoscience to medical diagnostics. Much work has been done to characterize the fidelity with which the geometrical features of the medium can be reconstructed and multiple resolution criteria have been proposed depending on the wave-matter interaction model used to decode the wave speed map from scattering measurements. However, these criteria do not define the accuracy with which the wave speed values can be reconstructed. Using two-dimensional simulations, it is shown that the first-arrival traveltime predicted by ray theory can be an accurate representation of the arrival of a pulse first break even in the presence of diffraction and other phenomena that are not accounted for by ray theory. As a result, ray-based tomographic inversions can yield accurate wave speed estimations also when the size of a sound speed anomaly is smaller than the resolution length of the inversion method provided that traveltimes are estimated from the signal first break. This increased sensitivity however renders the inversion more susceptible to noise since the amplitude of the signal around the first break is typically low especially when three-dimensional anomalies are considered. PMID- 27369140 TI - Near-field/far-field array manifold of an acoustic vector-sensor near a reflecting boundary. AB - The acoustic vector-sensor (a.k.a. the vector hydrophone) is a practical and versatile sound-measurement device, with applications in-room, open-air, or underwater. It consists of three identical uni-axial velocity-sensors in orthogonal orientations, plus a pressure-sensor-all in spatial collocation. Its far-field array manifold [Nehorai and Paldi (1994). IEEE Trans. Signal Process. 42, 2481-2491; Hawkes and Nehorai (2000). IEEE Trans. Signal Process. 48, 2981 2993] has been introduced into the technical field of signal processing about 2 decades ago, and many direction-finding algorithms have since been developed for this acoustic vector-sensor. The above array manifold is subsequently generalized for outside the far field in Wu, Wong, and Lau [(2010). IEEE Trans. Signal Process. 58, 3946-3951], but only if no reflection-boundary is to lie near the acoustic vector-sensor. As for the near-boundary array manifold for the general case of an emitter in the geometric near field, the far field, or anywhere in between-this paper derives and presents that array manifold in terms of signal processing mathematics. Also derived here is the corresponding Cramer-Rao bound for azimuth-elevation-distance localization of an incident emitter, with the reflected wave shown to play a critical role on account of its constructive or destructive summation with the line-of-sight wave. The implications on source localization are explored, especially with respect to measurement model mismatch in maximum-likelihood direction finding and with regard to the spatial resolution between coexisting emitters. PMID- 27369141 TI - Effectiveness of nonporous windscreens for infrasonic measurements. AB - This paper deals with nonporous windscreens used for reducing noise in infrasonic measurements. A model of sound transmission using a modal approach is derived. The system is a square plate coupled with a cavity. The model agrees with finite element simulations and measurements performed on two windscreens: a cubic windscreen using a material recommended by Shams, Zuckerwar, and Sealey [J. Acoust. Soc. Am. 118, 1335-1340 (2005)] and an optimized flat windscreen made out of aluminum. Only the latter was found to couple acoustical waves below 10 Hz without any attenuation. Moreover, wind noise reduction measurements show that nonporous windscreens perform similarly as a pipe array by averaging the pressure fluctuations. These results question the assumptions of Shams et al. and Zuckerwar [J. Acoust. Soc. Am. 127, 3327-3334 (2010)] about compact nonporous windscreens design and effectiveness. PMID- 27369142 TI - The mechanisms of subharmonic tone generation in a synthetic larynx model. AB - The sound spectra obtained in a synthetic larynx exhibited subharmonic tones that are characteristic for diplophonia. Although the generation of subharmonics is commonly associated with asymmetrically oscillating vocal folds, the synthetic elastic vocal folds showed symmetrical oscillations. The amplitudes of the subharmonics decreased with an increasing lateral diameter of the supraglottal channel, which indicates a strong dependence of the supraglottal boundary conditions. Investigations of the supraglottal flow field revealed small cycle-to cycle variations of the static pressure in the region of the pulsatile glottal jet as the origin of the first subharmonic tone. It is located at half the fundamental frequency of the vocal fold oscillation. A principle component analysis of the supraglottal flow field with the fully developed glottal jet revealed a large recirculation area in the second spatial eigenvector which deflected the glottal jet slightly in a perpendicular direction of the jet axis. The rotation direction of the recirculation area changed with different oscillation cycles between clockwise and counterclockwise. As both directions were uniformly distributed across all acquired oscillation cycles, a cycle-wise change can be assumed. It is concluded that acoustic subharmonics are generated by small fluctuations of the glottal jet location favored by small lateral diameters of the supraglottal channel. PMID- 27369144 TI - The acoustic power of a vibrating clamped circular plate revisited in the wide low frequency range using expansion into the radial polynomials. AB - This study deals with the classical problem of sound radiation of an excited clamped circular plate embedded into a flat rigid baffle. The system of the two coupled differential equations is solved, one for the excited and damped vibrations of the plate and the other one-the Helmholtz equation. An approach using the expansion into radial polynomials leads to results for the modal impedance coefficients useful for a comprehensive numerical analysis of sound radiation. The results obtained are accurate and efficient in a wide low frequency range and can easily be adopted for a simply supported circular plate. The fluid loading is included providing accurate results in resonance. PMID- 27369145 TI - Specific features of a stopped pipe blown by a turbulent jet: Aeroacoustics of the panpipes. AB - Flute-like instruments with a stopped pipe were widely used in ancient cultures and continue to be used in many musical expressions throughout the globe. They offer great flexibility in the input control parameters, allowing for large excursions in the flux and in the geometrical configuration for the lips of the instrumentalist. For instance, the transverse offset of the jet axis relative to the labium can be shifted beyond the operational limits found in open-open pipes, and the total jet flux can be increased up to values that produce highly turbulent jets while remaining on the first oscillating regime. Some of the fundamental aspects of the acoustics and hydrodynamics of this kind of instrument are studied, like the instability of the jet wave and the static aerodynamic balance in the resonator. A replica of an Andean siku has been created to observe, through the Schlieren flow visualization, the behavior of both excitation and resonator of the instrument. PMID- 27369143 TI - Wideband acoustic activation and detection of droplet vaporization events using a capacitive micromachined ultrasonic transducer. AB - An ongoing challenge exists in understanding and optimizing the acoustic droplet vaporization (ADV) process to enhance contrast agent effectiveness for biomedical applications. Acoustic signatures from vaporization events can be identified and differentiated from microbubble or tissue signals based on their frequency content. The present study exploited the wide bandwidth of a 128-element capacitive micromachined ultrasonic transducer (CMUT) array for activation (8 MHz) and real-time imaging (1 MHz) of ADV events from droplets circulating in a tube. Compared to a commercial piezoelectric probe, the CMUT array provides a substantial increase of the contrast-to-noise ratio. PMID- 27369146 TI - Individual differences in processing pitch contour and rise time in adults: A behavioral and electrophysiological study of Cantonese tone merging. AB - One way to understand the relationship between speech perception and production is to examine cases where the two dissociate. This study investigates the hypothesis that perceptual acuity reflected in event-related potentials (ERPs) to rise time of sound amplitude envelope and pitch contour [reflected in the mismatch negativity (MMN)] may associate with individual differences in production among speakers with otherwise comparable perceptual abilities. To test this hypothesis, advantage was taken of an on-going sound change-tone merging in Cantonese, and compared the ERPs between two groups of typically developed native speakers who could discriminate the high rising and low rising tones with equivalent accuracy but differed in the distinctiveness of their production of these tones. Using a passive oddball paradigm, early positive-going EEG components to rise time and MMN to pitch contour were elicited during perception of the two tones. Significant group differences were found in neural responses to rise time rather than pitch contour. More importantly, individual differences in efficiency of tone discrimination in response latency and magnitude of neural responses to rise time were correlated with acoustic measures of F0 offset and rise time differences in productions of the two rising tones. PMID- 27369147 TI - Introduction to the special issue on acoustic metamaterials. PMID- 27369148 TI - Membrane- and plate-type acoustic metamaterials. AB - Over the past decade there has been a great amount of research effort devoted to the topic of acoustic metamaterials (AMMs). The recent development of AMMs has enlightened the way of manipulating sound waves. Several potential applications such as low-frequency noise reduction, cloaking, angular filtering, subwavelength imaging, and energy tunneling have been proposed and implemented by the so-called membrane- or plate-type AMMs. This paper aims to offer a thorough overview on the recent development of membrane- or plate-type AMMs. The underlying mechanism of these types of AMMs for tuning the effective density will be examined first. Four different groups of membrane- or plate-type AMMs (membranes with masses attached, plates with masses attached, membranes or plates without masses attached, and active AMMs) will be reviewed. The opportunities, limitations, and challenges of membrane- or plate-type AMMs will be also discussed. PMID- 27369149 TI - Evaluation of the resolution of a metamaterial acoustic leaky wave antenna. AB - Acoustic antennas have long been utilized to directionally steer acoustic waves in both air and water. Typically, these antennas are comprised of arrays of active acoustic elements, which are electronically phased to steer the acoustic profile in the desired direction. A new technology, known as an acoustic leaky wave antenna (LWA), has recently been shown to achieve directional steering of acoustic waves using a single active transducer coupled to a transmission line passive aperture. The LWA steers acoustic energy by preferential coupling to an input frequency and can be designed to steer from backfire to endfire, including broadside. This paper provides an analysis of resolution as a function of both input frequency and antenna length. Additionally, the resolution is compared to that achieved using an array of active acoustic elements. PMID- 27369150 TI - Exploiting the leaky-wave properties of transmission-line metamaterials for single-microphone direction finding. AB - A transmission-line acoustic metamaterial is an engineered, periodic arrangement of relatively small unit-cells, the acoustic properties of which can be manipulated to achieve anomalous physical behaviours. These exotic properties open the door to practical applications, such as an acoustic leaky-wave antenna, through the implementation of radiating channels along the metamaterial. In the transmitting mode, such a leaky-wave antenna is capable of steering sound waves in frequency-dependent directions. Used in reverse, the antenna presents a well defined direction-frequency behaviour. In this paper, an acoustic leaky-wave structure is presented in the receiving mode. It is shown that it behaves as a sound source direction-finding device using only one sensor. After a general introduction of the acoustic leaky-wave antenna concept, its radiation pattern and radiation efficiency are expressed in closed form. Then, numerical simulations and experimental assessments of the proposed transmission-line based structure, implementing only one sensor at one termination, are presented. It is shown that such a structure is capable of finding the direction of an incoming sound wave, from backward to forward, based on received sound power spectra. This introduces the concept of sound source localization without resorting to beam steering techniques based on multiple sensors. PMID- 27369151 TI - Validation of low frequency noise attenuation using locally resonant patches. AB - Since conventional silencers in acoustic ducts have problems of size limitations at low frequencies and being prone to high backpressure, locally resonant aluminum patches are introduced in acoustic duct walls aiming at creating frequency stop bands in the low frequency region (below 1 KHz). With these flush mounted patches, promising noise reductions, with no such drawbacks, can be obtained, building on local resonance phenomenon implemented in acoustic metamaterials techniques. The objective of the current paper is to experimentally validate the performance of an array of flexible side-wall-mounted patches inside ducts. The experimental results are compared with Analytical Green's function method as well as Numerical Finite Element Method and a close agreement was found. The results show that the presence of the patches singly or periodically can play a prominent role in designing any acoustic bandgap materials. The effect of the arrays of patches on the effective dynamic density and bulk modulus has also been investigated. PMID- 27369152 TI - Sound attenuation in ducts using locally resonant periodic aluminum patches. AB - In recent years, the control of low frequency noise has received a lot of attention for several applications. Traditional passive noise control techniques using Helmholtz resonators have size limitations in the low frequency range because of the long wavelength. Promising noise reductions, with flush mounted aluminum patches with no size problems can be obtained using local resonance phenomenon implemented in acoustic metamaterial techniques. The objective of this work is to introduce locally resonant thin aluminum patches flush mounted to a duct walls aiming at creating frequency stop bands in a specific frequency range. Green's function is used within the framework of interface response theory to predict the amount of attenuation of the local resonant patches. The two-port theory and finite elements are also used to predict the acoustic performance of these patches. No flow measurements were conducted and show good agreement with the models. The effect of varying the damping and the masses of the patches are used to expand the stop bandwidth and the effect of both Bragg scattering and the locally resonant mechanisms was demonstrated using mathematical models. The effect of the arrays of patches on the effective dynamic density and bulk modulus has also been investigated. PMID- 27369153 TI - Control of elastic wave propagation in one-dimensional piezomagnetic phononic crystals. AB - Two ways of controlling the acoustic waves propagation by external inductance or capacitance in a one-dimensional (1-D) piezomagnetic phononic crystal are investigated. The structure is made of identical bars, constituted of a piezomagnetic material, surrounded by a coil and connected to an external impedance. A model of propagation of longitudinal elastic waves through the periodic structure is developed and the dispersion equation is obtained. Reflection and transmission coefficients are derived from a 2 * 2 transfer matrix formalism that also allows for the calculation of elastic effective parameters (density, Young modulus, speed of sound, impedance). The effect of shunting impedances is numerically investigated. The results reveal that a connected external inductance tunes the Bragg band gaps of the 1-D phononic crystal. When the elements are connected via a capacitance, a hybridization gap, due to the resonance of the LC circuit made of the piezomagnetic element and the capacitance, coexists with the Bragg band gap. The value of the external capacitance modifies the boundaries of both gaps. Calculation of the effective characteristics of the phononic crystal leads to an analysis of the physical mechanisms involved in the wave propagation. When periodically connected to external capacitances, a homogeneous piezomagnetic stack behaves as a dispersive tunable metamaterial. PMID- 27369154 TI - Tunable phononic crystals based on piezoelectric composites with 1-3 connectivity. AB - Phononic crystals made of piezoelectric composites with 1-3 connectivity are studied theoretically and experimentally. It is shown that they present Bragg band gaps that depend on the periodic electrical boundary conditions. These structures have improved properties compared to phononic crystals composed of bulk piezoelectric elements, especially the existence of larger band gaps and the fact that they do not require severe constraints on their aspect ratios. Experimental results present an overall agreement with the theoretical predictions and clearly show that the pass bands and stop bands of the device under study are easily tunable by only changing the electrical boundary conditions applied on each piezocomposite layer. PMID- 27369155 TI - A single-phase elastic hyperbolic metamaterial with anisotropic mass density. AB - Wave propagation can be manipulated at a deep subwavelength scale through the locally resonant metamaterial that possesses unusual effective material properties. Hyperlens due to metamaterial's anomalous anisotropy can lead to superior-resolution imaging. In this paper, a single-phase elastic metamaterial with strongly anisotropic effective mass density has been designed. The proposed metamaterial utilizes the independently adjustable locally resonant motions of the subwavelength-scale microstructures along the two principal directions. High anisotropy in the effective mass densities obtained by the numerical-based effective medium theory can be found and even have opposite signs. For practical applications, shunted piezoelectric elements are introduced into the microstructure to tailor the effective mass density in a broad frequency range. Finally, to validate the design, an elastic hyperlens made of the single-phase hyperbolic metamaterial is proposed with subwavelength longitudinal wave imaging illustrated numerically. The proposed single-phase hyperbolic metamaterial has many promising applications for high resolution damage imaging in nondestructive evaluation and structural health monitoring. PMID- 27369156 TI - Two-dimensional locally resonant elastic metamaterials with chiral comb-like interlayers: Bandgap and simultaneously double negative properties. AB - In this paper, bandgap and dynamic effective properties of two-dimensional elastic metamaterials with a chiral comb-like interlayer are studied by using the finite element method. The effects of the geometrical parameters of the chiral comb-like interlayer on the band edges are investigated and discussed. Combined with the analysis of the vibration modes at the band edges, equivalent spring mass/pendulum models are developed to investigate the mechanisms of the bandgap generation. The analytically predicted results of the band edges, including the frequency where the double negative properties appear, and the numerical ones are generally in good agreement. The research findings in this paper have relevant engineering applications of the elastic metamaterials in the low frequency range. PMID- 27369157 TI - Flexural wave cloaking via embedded cylinders with systematically varying thicknesses. AB - Simulations of flexural wave cloaking from multiple scattering events that are achieved by embedded cylinders in a thin plate are performed. Minimization of refraction is performed using small surrounding cylinders with varying thickness in radial and angular directions, respectively. The thickness variations render the effective wave speed lower in the radial direction and higher in the angular direction compared to the speed in the surrounding media, which results in the cloaking effect. In order to verify the feasibility of this approach, 15 layers of cylinders are placed around the blocked area. The multiple-scattering method is used to predict wave propagations and to take the interactions between cylinders into account. The effects of the thickness variation on the cloaking performance are analyzed. The results demonstrate that minimal scattering is achieved when the area of interest is surrounded by the thickness-varying cylinders. PMID- 27369158 TI - Anisotropic acoustic metafluid for underwater operation. AB - The paper presents a method to design and characterize mechanically robust solid acoustic metamaterials suitable for operation in dense fluids such as water. These structures, also called metafluids, behave acoustically as inertial fluids characterized by anisotropic mass densities and isotropic bulk modulus. The method is illustrated through the design and experimental characterization of a metafluid consisting of perforated steel plates held together by rubber coated magnetic spacers. The spacers are very effective at reducing the effective shear modulus of the structure, and therefore effective at minimizing the ensuing coupling between the shear and pressure waves inside the solid effective medium. Inertial anisotropy together with fluid-like acoustic behavior are key properties that bring transformation acoustics in dense fluids closer to reality. PMID- 27369159 TI - Analytical analysis of slow and fast pressure waves in a two-dimensional cellular solid with fluid-filled cells. AB - Wave propagation in cellular and porous media is widely studied due to its abundance in nature and industrial applications. Biot's theory for open-cell media predicts the existence of two simultaneous pressure waves, distinguished by its velocity. A fast wave travels through the solid matrix, whereas a much slower wave is carried by fluid channels. In closed-cell materials, the slow wave disappears due to a lack of a continuous fluid path. However, recent finite element (FE) simulations done by the authors of this paper also predict the presence of slow pressure waves in saturated closed-cell materials. The nature of the slow wave is not clear. In this paper, an equivalent unit cell of a medium with square cells is proposed to permit an analytical description of the dynamics of such a material. A simplified FE model suggests that the fluid-structure interaction can be fully captured using a wavenumber-dependent spring support of the vibrating cell walls. Using this approach, the pressure wave behavior can be calculated with high accuracy, but with less numerical effort. Finally, Rayleigh's energy method is used to investigate the coexistence of two waves with different velocities. PMID- 27369160 TI - Random acoustic metamaterial with a subwavelength dipolar resonance. AB - The effective velocity and attenuation of longitudinal waves through random dispersions of rigid, tungsten-carbide beads in an elastic matrix made of epoxy resin in the range of beads volume fraction 2%-10% are determined experimentally. The multiple scattering model proposed by Luppe, Conoir, and Norris [J. Acoust. Soc. Am. 131(2), 1113-1120 (2012)], which fully takes into account the elastic nature of the matrix and the associated mode conversions, accurately describes the measurements. Theoretical calculations show that the rigid particles display a local, dipolar resonance which shares several features with Minnaert resonance of bubbly liquids and with the dipolar resonance of core-shell particles. Moreover, for the samples under study, the main cause of smoothing of the dipolar resonance of the scatterers and the associated variations of the effective mass density of the dispersions is elastic relaxation, i.e., the finite time required for the shear stresses associated to the translational motion of the scatterers to propagate through the matrix. It is shown that its influence is governed solely by the value of the particle to matrix mass density contrast. PMID- 27369161 TI - Acoustic Poisson-like effect in periodic structures. AB - Redirection of acoustic energy by 90 degrees is shown to be possible in an otherwise acoustically transparent sonic crystal. An unresponsive "deaf" antisymmetric mode is excited by matching Bragg scattering with a quadrupole scatterer resonance. The dynamic effect causes normal unidirectional wave motion to strongly couple to perpendicular motion, analogous to the quasi-static Poisson effect in solids. The Poisson-like effect is demonstrated using the first flexural resonance in cylindrical shells of elastic solids. Simulations for a finite array of acrylic shells that are impedance and index matched to water show dramatic acoustic energy redirection in an otherwise acoustically transparent medium. PMID- 27369162 TI - A high transmission broadband gradient index lens using elastic shell acoustic metamaterial elements. AB - The use of cylindrical elastic shells as elements in acoustic metamaterial devices is demonstrated through simulations and underwater measurements of a cylindrical-to-plane wave lens. Transformation acoustics of a circular region to a square dictate that the effective density in the lens remain constant and equal to that of water. Piecewise approximation to the desired effective compressibility is achieved using a square array with elements based on the elastic shell metamaterial concept developed by Titovich and Norris [J. Acoust. Soc. Am. 136(4), 1601-1609 (2014)]. The sizes of the elements are chosen based on availability of shells, minimizing fabrication difficulties. The tested device is neutrally buoyant comprising 48 elements of nine different types of commercial shells made from aluminum, brass, copper, and polymers. Simulations indicate a broadband range in which the device acts as a cylindrical to plane wave lens. The experimental findings confirm the broadband quadropolar response from approximately 20 to 40 kHz, with positive gain of the radiation pattern in the four plane wave directions. PMID- 27369163 TI - Numerical investigation of amplitude-dependent dynamic response in acoustic metamaterials with nonlinear oscillators. AB - The amplitude-dependent dynamic response in acoustic metamaterials having nonlinear local oscillator microstructures is studied using numerical simulations on representative discrete mass-spring models. Both cubically nonlinear hardening and softening local oscillator cases are considered. Single frequency, bi frequency, and wave packet excitations at low and high amplitude levels were used to interrogate the models. The propagation and attenuation characteristics of harmonic waves in a tunable frequency range is found to correspond to the amplitude and nonlinearity-dependent shifts in the local resonance bandgap for such nonlinear acoustic metamaterials. A predominant shift in the propagated wave spectrum towards lower frequencies is observed. Moreover, the feasibility of amplitude and frequency-dependent selective filtering of composite signals consisting of individual frequency components which fall within propagating or attenuating regimes is demonstrated. Further enrichment of these wave manipulation mechanisms in acoustic metamaterials using different combinations of nonlinear microstructures presents device implications for acoustic filters and waveguides. PMID- 27369164 TI - A nonlinear acoustic metamaterial: Realization of a backwards-traveling second harmonic sound wave. AB - An ordinary waveguide with periodic vibration plates and side holes can realize an acoustic metamaterial that simultaneously possesses a negative bulk modulus and a negative mass density. The study is further extended to a nonlinear case and it is predicted that a backwards-traveling second-harmonic sound wave can be obtained through the nonlinear propagation of a sound wave in such a metamaterial. PMID- 27369165 TI - Focusing, refraction, and asymmetric transmission of elastic waves in solid metamaterials with aligned parallel gaps. AB - Gradient index (GRIN), refractive, and asymmetric transmission devices for elastic waves are designed using a solid with aligned parallel gaps. The gaps are assumed to be thin so that they can be considered as parallel cracks separating elastic plate waveguides. The plates do not interact with one another directly, only at their ends where they connect to the exterior solid. To formulate the transmission and reflection coefficients for SV- and P-waves, an analytical model is established using thin plate theory that couples the waveguide modes with the waves in the exterior body. The GRIN lens is designed by varying the thickness of the plates to achieve different flexural wave speeds. The refractive effect of SV waves is achieved by designing the slope of the edge of the plate array, and keeping the ratio between plate length and flexural wavelength fixed. The asymmetric transmission of P-waves is achieved by sending an incident P-wave at a critical angle, at which total conversion to SV-wave occurs. An array of parallel gaps perpendicular to the propagation direction of the reflected waves stop the SV-wave but let P-waves travel through. Examples of focusing, steering, and asymmetric transmission devices are discussed. PMID- 27369166 TI - Use of complex frequency plane to design broadband and sub-wavelength absorbers. AB - The reflection of sound of frequency below 1 kHz, by a rigid-backed structure that contains sub-wavelength resonators is studied in this work. In particular, only single mode reflected waves are considered, an approximation which is accurate in this low frequency regime. A method of analysis of absorption that uses the structure of the reflection coefficient in the complex frequency plane is proposed. In the absence of losses, the reflection coefficient supports pairs of poles and zeros that are complex conjugate and which have imaginary parts linked to the energy leakage by radiation. When losses are introduced and balanced to the leakage, the critical coupling condition is satisfied and total absorption is obtained. Examples of a slot resonator and of multiple Helmholtz resonators are analyzed to obtain both narrow and broadband total absorption. PMID- 27369167 TI - Scattering reduction of an acoustically hard cylinder covered with layered pentamode metamaterials. AB - Transformational acoustics offers the theoretical possibility of cloaking obstacles within fluids, provided metamaterials having continuously varying bulk moduli and densities can be found or constructed. Realistically, materials with the proper, continuously varying anisotropies do not presently exist. However, discretely layered cloaks having constant material parameters within each layer may be a viable alternative in practice. The present work considers a range of cloaks, from those comprised of fluid layers that are isotropic in bulk moduli with anisotropic density (inertial cloaks) to those having anisotropic bulk moduli and isotropic density (pentamode cloaks). In this paper an analytical solution is obtained for the case of plane wave scattering from a submerged rigid cylinder covered with a multilayered cylindrical cloak composed of discrete anisotropic fluid layers. An investigation of the parameter space defining such cloaks is undertaken with the goal of minimizing the far-field scattered pressure, using layer constituent anisotropic properties (density and bulk modulus) constrained to lie within reasonable ranges relative to those of water. PMID- 27369168 TI - Generalized metamaterials: Definitions and taxonomy. AB - This article reviews the development of metamaterials (MM), starting from Newton's discovery of the wave equation, and ends with a discussion of the need for a technical taxonomy (classification) of these materials, along with a better defined definition of metamaterials. It is intended to be a technical definition of metamaterials, based on a historical perspective. The evolution of MMs began with the discovery of the wave equation, traceable back to Newton's calculation of the speed of sound. The theory of sound evolved to include quasi-statics (Helmholtz) and the circuit equations of Kirchhoff's circuit laws, leading to the ultimate development of Maxwell's equations and the equation for the speed of light. Be it light, or sound, the speed of the wave-front travel defines the wavelength, and thus the quasi-static (QS) approximation. But there is much more at stake than QSs. Taxonomy requires a proper statement of the laws of physics, which includes at least the six basic network postulates: (P1) causality (non causal/acausal), (P2) linearity (non-linear), (P3) real (complex) time response, (P4) passive (active), (P5) time-invariant (time varying), and (P6) reciprocal (non-reciprocal). These six postulates are extended to include MMs. PMID- 27369169 TI - Unidirectional acoustic probe based on the particle velocity gradient. AB - This paper presents the foundations of a unidirectional acoustic probe based on the particle velocity gradient. Highly directional characteristics play a key role in reducing the influence of undesired acoustic sources. These characteristics can be achieved by using multiple acoustic sensors in a spatial gradient arrangement. Two particle velocity sensors possessing the figure eight directivity pattern were used in a first-order gradient configuration to yield a unidirectional probe that can reject most excitations originating from both sides and the rear. The effects of key parameters are thoroughly discussed, and the proposed theory is validated in practice. PMID- 27369170 TI - Measured depth-dependence of waveguide invariant in shallow water with a summer profile. AB - Acoustic-intensity striation patterns were measured in the time-frequency domain using an L-shaped array and two simultaneously towed broadband (350-650 Hz) sources at depths above and below the thermocline under summer profile conditions. Distributions of the waveguide invariant parameter beta, extracted from the acoustic striation patterns, peak at different values when receivers are above or below the thermocline for a source that is below the thermocline. However, the distributions show similar characteristics when the source is above the thermocline. Experimental results are verified by a numerical analysis of phase slowness, group slowness, and relative amplitudes of acoustic modes. PMID- 27369171 TI - Subcortical neural representation to Mandarin pitch contours in American and Chinese newborns. AB - Voice pitch carries important information for speech understanding. This study examines the neural representation of voice pitch at the subcortical level, as reflected by the scalp-recorded frequency-following responses from ten American and ten Chinese newborns. By utilizing a set of four distinctive Mandarin pitch contours that mimic the English vowel /yi/, the results indicate that the rising and dipping pitch contours produce significantly better tracking accuracy and larger response amplitudes than the falling pitch contour. This finding suggests a hierarchy of potential stimuli when testing neonates who are born in a tonal or non-tonal linguistic environment. PMID- 27369172 TI - Passive localization in the deep ocean based on cross-correlation function matching. AB - Passive localization of a sound source in the deep ocean is investigated in this study. The source can be localized by taking advantage of a cross-correlation function matching technique. When a two-sensor vertical array is used in the deep ocean, two types of side lobe curves appear in the ambiguity surface of the localization. The side lobe curves are analytically expressed and they are then used as indicators of the localization result instead of the scanning point with the maximum power. Simulation and experiment demonstrate the performance of the proposed passive localization method. PMID- 27369173 TI - Sound transmission in a duct with a side-branch tube array mounted periodically. AB - This paper presents a theoretical study of sound propagation in a duct with a tube array flush-mounted periodically. The underlying wave interaction is analyzed by the transfer matrix method, and validated by the numerical simulation. With identical tubes, a particular situation is observed that the periodic distance and the tube length are "matched," leading to a strong coupling effect by Bragg reflection and tube resonance, resulting in a wide stopband in low frequency. Even when the tubes in the array are not identical, the Bragg reflection can still work to broaden the stopband which was originally contributed by tube resonances. PMID- 27369174 TI - Modeling listener perception of speaker similarity in dysarthria. AB - The current investigation contributes to a perceptual similarity-based approach to dysarthria characterization by utilizing an innovative statistical approach, multinomial logistic regression with sparsity constraints, to identify acoustic features underlying each listener's impressions of speaker similarity. The data driven approach also permitted an examination of the effect of clinical experience on listeners' impressions of similarity. Listeners, irrespective of level of clinical experience, were found to rely on similar acoustic features during the perceptual sorting task, known as free classification. Overall, the results support the continued advancement of a similarity-based approach to characterizing the communication disorders associated with dysarthria. PMID- 27369175 TI - English-speaking preschoolers can use phrasal prosody for syntactic parsing. AB - This study tested American preschoolers' ability to use phrasal prosody to constrain their syntactic analysis of locally ambiguous sentences containing noun/verb homophones (e.g., [The baby flies] [hide in the shadows] vs [The baby] [flies his kite], brackets indicate prosodic boundaries). The words following the homophone were masked, such that prosodic cues were the only disambiguating information. In an oral completion task, 4- to 5-year-olds successfully exploited the sentence's prosodic structure to assign the appropriate syntactic category to the target word, mirroring previous results in French (but challenging previous English-language results) and providing cross-linguistic evidence for the role of phrasal prosody in children's syntactic analysis. PMID- 27369176 TI - Underwater sound of rigid-hulled inflatable boats. AB - Underwater sound of rigid-hulled inflatable boats was recorded 142 times in total, over 3 sites: 2 in southern British Columbia, Canada, and 1 off Western Australia. Underwater sound peaked between 70 and 400 Hz, exhibiting strong tones in this frequency range related to engine and propeller rotation. Sound propagation models were applied to compute monopole source levels, with the source assumed 1 m below the sea surface. Broadband source levels (10-48 000 Hz) increased from 134 to 171 dB re 1 MUPa @ 1 m with speed from 3 to 16 m/s (10-56 km/h). Source power spectral density percentile levels and 1/3 octave band levels are given for use in predictive modeling of underwater sound of these boats as part of environmental impact assessments. PMID- 27369177 TI - A model of ultrasound-enhanced diffusion in a biofilm. AB - A stochastic model is presented for nanoparticle transport in a biofilm to explain how the combination of acoustic oscillations and intermittent retention due to interaction with the pore walls of the biofilm leads to diffusion enhancement. An expression for the effective diffusion coefficient was derived that varies with the square of the oscillation velocity amplitude. This expression was validated by comparison of an analytical diffusion solution to the stochastic model prediction. The stochastic model was applied to an example problem associated with liposome penetration into a hydrogel, and it was found to yield solutions in which liposome concentration varied exponentially with distance into the biofilm. PMID- 27369178 TI - Is markerless acquisition technique adequate for speech production? AB - In this study, the precision of markerless acquisition techniques have been assessed when used to acquire articulatory data for speech production studies. Two different markerless systems have been evaluated and compared to a marker based one. The main finding is that both markerless systems provide a reasonable result during normal speech and the quality is uneven during fast articulated speech. The quality of the data is dependent on the temporal resolution of the markerless system. PMID- 27369179 TI - Integration of partial information for spoken and written sentence recognition by older listeners. AB - Older adults have difficulty understanding speech in challenging listening environments. Combining multisensory signals may facilitate speech recognition. This study measured recognition of interrupted spoken and written sentences by older adults for different preserved stimulus proportions. Unimodal performance was first examined when only interrupted text or speech stimuli were presented. Multimodal performance with concurrently presented text and speech stimuli was tested with delayed and simultaneous participant responses. Older listeners performed better in unimodal speech-only compared to text-only conditions across all proportions preserved. Performance was also better in delayed multimodal conditions. Comparison to a younger sample suggests age-related amodal processing declines. PMID- 27369180 TI - Mistuning detection performance of ferrets in a go/no-go task. AB - The harmonic structure of sounds is an important grouping cue in auditory scene analysis. The ability of ferrets to detect mistuned harmonics was measured using a go/no-go task paradigm. Psychometric functions plotting sensitivity as a function of degree of mistuning were used to evaluate behavioral performance using signal detection theory. The mean (+/- standard error of the mean) threshold for mistuning detection was 0.8 +/- 0.1 Hz, with sensitivity indices and reaction times depending on the degree of mistuning. These data provide a basis for investigation of the neural basis for the perception of complex sounds in ferrets, an increasingly used animal model in auditory research. PMID- 27369181 TI - Uncovering the acoustic vowel space of a previously undescribed language: The vowels of Nambo. AB - This study presents the first acoustic description of the vowel space of a Papuan language-Nambo, spoken in southern Papua New Guinea-based on duration and first and second formant measurements from 19 adult male and female speakers across three age groups (young, middle-aged, senior). Phonemically, Nambo has six full vowels /i, e, ae, alpha, o, u/ and a reduced vowel tentatively labeled /e/. Unlike the full vowels, the quality of /e/ showed great variation: seniors' and young females' realizations tended to be more open and retracted than those by young males, while middle-aged speakers' productions fell between these two variants. PMID- 27369182 TI - Type I error rates of multi-arm multi-stage clinical trials: strong control and impact of intermediate outcomes. AB - BACKGROUND: The multi-arm multi-stage (MAMS) design described by Royston et al. [Stat Med. 2003;22(14):2239-56 and Trials. 2011;12:81] can accelerate treatment evaluation by comparing multiple treatments with a control in a single trial and stopping recruitment to arms not showing sufficient promise during the course of the study. To increase efficiency further, interim assessments can be based on an intermediate outcome (I) that is observed earlier than the definitive outcome (D) of the study. Two measures of type I error rate are often of interest in a MAMS trial. Pairwise type I error rate (PWER) is the probability of recommending an ineffective treatment at the end of the study regardless of other experimental arms in the trial. Familywise type I error rate (FWER) is the probability of recommending at least one ineffective treatment and is often of greater interest in a study with more than one experimental arm. METHODS: We demonstrate how to calculate the PWER and FWER when the I and D outcomes in a MAMS design differ. We explore how each measure varies with respect to the underlying treatment effect on I and show how to control the type I error rate under any scenario. We conclude by applying the methods to estimate the maximum type I error rate of an ongoing MAMS study and show how the design might have looked had it controlled the FWER under any scenario. RESULTS: The PWER and FWER converge to their maximum values as the effectiveness of the experimental arms on I increases. We show that both measures can be controlled under any scenario by setting the pairwise significance level in the final stage of the study to the target level. In an example, controlling the FWER is shown to increase considerably the size of the trial although it remains substantially more efficient than evaluating each new treatment in separate trials. CONCLUSIONS: The proposed methods allow the PWER and FWER to be controlled in various MAMS designs, potentially increasing the uptake of the MAMS design in practice. The methods are also applicable in cases where the I and D outcomes are identical. PMID- 27369183 TI - [Operative treatment of anterior cruciate ligament ruptures with autologous hamstring tendons in children and adolescents]. PMID- 27369184 TI - [Elderly trauma patients with proximal femur fractures : Statistical evaluation of regular process data from a trauma center for the elderly]. AB - BACKGROUND/AIMS: Proximal femoral fractures are one of the most frequently occurring injuries among elderly people. High rates of inpatient treatment indicate the importance of optimized clinical care. OBJECTIVES: Based on selected outcome parameters in elderly trauma patients with proximal femoral fractures, the current situation of medical care in a trauma center for geriatric patients is presented. METHODS: For a descriptive evaluation of outcome parameters, 250 patients aged 70 years and older have been included. A clinical register of a trauma center for the elderly served as the database. RESULTS: The average length of stay was approximately 25 days. Sixty-seven percent of the patients underwent surgical treatment within 24 h of admission to the hospital. More than half of the patients were taking anticoagulant drugs. Around 18 % of patients presented with one or more complications. Mortality rate was 5.2 %. Thirty-two percent of those patients who had been living at home before admission had been discharged to a nursing home. DISCUSSION AND CONCLUSIONS: Analyzing the data of a trauma registry enables critical reflection upon the clinical outcome of interdisciplinary treatment procedures. The low rate of mortality may be a result of the geriatric co-treatment, starting right from admission. It remains unclear whether the influence of preoperative interdisciplinary treatment outweighs the effect of a timely surgical procedure. PMID- 27369185 TI - Synaptic functions of the IQSEC family of ADP-ribosylation factor guanine nucleotide exchange factors. AB - Postsynaptic scaffolding proteins interact with numerous synaptic proteins to ensure the organization and specialization of functional excitatory and inhibitory synapses. IQSECs (IQ motif and SEC7 domain-containing proteins) are a class of ADP ribosylation factor-guanine nucleotide exchange factors (ARF-GEFs), whose functions are beginning to be understood as both scaffolding and signaling proteins. Specifically, IQSEC1 binds to PSD-95, and IQSEC2 functions as a regulator of AMPA receptor trafficking at excitatory synapses, whereas IQSEC3 interacts with gephyrin to promote inhibitory synapse development. Here, I review the currently known findings on IQSECs and discuss the possible relations between dysfunctions of IQSECs and the pathophysiology of brain disorders. PMID- 27369186 TI - The Association Between Clinical Characteristics of Migraine and Brain GABA Levels: An Exploratory Study. AB - Migraine is prevalent and disabling yet is poorly understood. One way to better understand migraine is to examine its clinical characteristics and potential biomarkers such as gamma-aminobutyric acid (GABA). The primary objective of this study was to explore whether relevant disease characteristics of migraine are associated with brain GABA levels. Twenty adults fulfilling the established diagnostic criteria for migraine and 20 age- and gender-matched controls completed this cross-sectional study. Pain, central sensitization, negative emotional state, and perceived disability were measured using Short-form McGill Pain Questionnaire-2, Central Sensitization Inventory, Depression Anxiety Stress Scales-21, and Headache Impact Test-6, respectively. Secondary analysis of brain GABA levels of the same cohort measured using proton magnetic resonance spectroscopy was conducted. The migraine group had significantly higher scores than the control group on pain, central sensitization, and disability. Correlation analyses showed fair positive association between GABA levels and pain and central sensitization scores. No association was found between GABA levels and emotional state and disability. These findings are preliminary evidence supporting the use of questionnaires and GABA levels in characterizing migraine better and broadening the diagnostic process. These findings also strengthen the rationale for the role of GABA in migraine pathophysiology and corroborate the potential of GABA as a migraine biomarker. PERSPECTIVE: Higher pain and central sensitization scores were associated with increased brain GABA levels in individuals with migraine. These findings offer preliminary evidence for the usefulness of measuring pain and central sensitization in migraine and provide some support for the possible role of GABA in migraine pathophysiology and its potential as a diagnostic marker. PMID- 27369187 TI - Hypercalcemic crisis associated with anastrozole use in a patient with breast cancer and primary hyperparathyroidism. PMID- 27369189 TI - [Not Available]. PMID- 27369188 TI - The landscape of bilateral adrenal incidentalomas associated with subclinical hypercortisolism. PMID- 27369191 TI - [Not Available]. PMID- 27369190 TI - [Not Available]. PMID- 27369192 TI - [Not Available]. PMID- 27369194 TI - [Not Available]. PMID- 27369193 TI - [Not Available]. PMID- 27369195 TI - [Not Available]. PMID- 27369196 TI - [Not Available]. PMID- 27369197 TI - [Not Available]. PMID- 27369198 TI - [Not Available]. PMID- 27369199 TI - [Not Available]. PMID- 27369200 TI - [Not Available]. PMID- 27369201 TI - [Not Available]. PMID- 27369202 TI - [Not Available]. PMID- 27369203 TI - [Not Available]. PMID- 27369204 TI - [Not Available]. PMID- 27369206 TI - [Not Available]. PMID- 27369205 TI - [Not Available]. PMID- 27369207 TI - [Not Available]. PMID- 27369208 TI - [Not Available]. PMID- 27369209 TI - [Not Available]. PMID- 27369210 TI - [Not Available]. PMID- 27369212 TI - [Not Available]. PMID- 27369211 TI - [Not Available]. PMID- 27369213 TI - [Not Available]. PMID- 27369214 TI - [Not Available]. PMID- 27369215 TI - [Not Available]. PMID- 27369216 TI - [Not Available]. PMID- 27369217 TI - [Not Available]. PMID- 27369218 TI - [Not Available]. PMID- 27369219 TI - [Not Available]. PMID- 27369220 TI - Estimating the risk of type-2 diabetes using obese-years in a contemporary population of the Framingham Study. AB - BACKGROUND: We have recently demonstrated that an obese-years construct is a better predictor of the risk of diabetes than the severity of body weight alone. However, these risk estimates were derived from a population cohort study initiated in 1948 that might not apply to the current population. OBJECTIVE: To validate an obese-years construct in estimating the risk of type-2 diabetes in a more contemporary cohort study. DESIGN: A total of 5,132 participants of the Framingham Offspring Study, initiated in 1972, were followed up for 45 years. Body mass index (BMI) above 29 kg/m(2) was multiplied by the number of years lived with obesity at that BMI to define the number of obese-years. Time dependent Cox regression was used to explore the association. RESULTS: The risk of type-2 diabetes increased significantly with increase in obese-years. Adjusted hazard ratios increased by 6% (95% CI: 5-7%) per additional 10 points of obese years. This ratio was observed to be similar in both men and women, but was 4% higher in current smokers than in never/ex-smokers. The Akaike Information Criterion confirmed that the Cox regression model with the obese-years construct was a stronger predictor of the risk of diabetes than a model including either BMI or the duration of obesity alone. CONCLUSIONS: In a contemporary cohort population, it was confirmed that the obese-years construct is strongly associated with an increased risk of type-2 diabetes. This suggests that both severity and the duration of obesity should be considered in future estimations of the burden of disease associated with obesity. PMID- 27369221 TI - Delays in antiretroviral therapy initiation among HIV-positive individuals: results of the positive living with HIV study. AB - BACKGROUND: Lack of early initiation of antiretroviral therapy (ART) remains a major health concern due to increased risk of premature mortality and further HIV transmission. This study explored CD4+ cell count monitoring in relation to delays in ART initiation among HIV-positive individuals in the Kathmandu Valley, Nepal, where ART coverage was only 23.7% in 2011. DESIGN: We recruited a total of 87 ART-naive, HIV-positive individuals aged 18 to 60 years through the networks of five non-government organizations working with HIV-positive individuals. We collected data on the history of ART initiation, CD4+ cell count monitoring, socio-demographic variables, perceived family support (measured with 10-item Nepali Family Support and Difficulty Scale), depression, and HIV symptom burden. Correlates of ART eligibility were examined using multivariable logistic regression analysis. RESULTS: A total of 72 of the 87 ART-naive participants (82.8%) had monitored their CD4+ cell count in the past 6 months. Of these, 36 (50%) participants were eligible for ART initiation with CD4+ cell count <350 cells/mm(3). A total of 12 participants had CD4+ cell count <200 cells/mm(3). Lower level of perceived family support was associated with 6.05-fold higher odds (95% confidence interval =1.95 to 18.73) of being ART eligible with a CD4+ cell count <350 cells/mm(3). CONCLUSIONS: High rate of delays in ART initiation and the strong association of low perceived family support with ART eligibility in our study participants suggest that HIV service providers should consider the role and impact of family support in influencing individual decisions to initiate ART among eligible HIV-positive individuals. PMID- 27369222 TI - [Not Available]. PMID- 27369223 TI - [Not Available]. PMID- 27369224 TI - [Not Available]. PMID- 27369225 TI - [Not Available]. PMID- 27369227 TI - [Not Available]. PMID- 27369226 TI - [Not Available]. PMID- 27369228 TI - [Not Available]. PMID- 27369229 TI - [Not Available]. PMID- 27369230 TI - [Not Available]. PMID- 27369231 TI - [Not Available]. PMID- 27369232 TI - [Not Available]. PMID- 27369233 TI - [Not Available]. PMID- 27369234 TI - [Not Available]. PMID- 27369235 TI - [Not Available]. PMID- 27369237 TI - [Not Available]. PMID- 27369236 TI - [Not Available]. PMID- 27369238 TI - [Not Available]. PMID- 27369239 TI - [Not Available]. PMID- 27369240 TI - [Not Available]. PMID- 27369242 TI - Implicit Theories and Offender Representativeness in Judgments About Sexual Crime. AB - Implicit theories structure the way people understand and respond to various human actions. Typically, people believe attributes are either fixed (entitists) or malleable (incrementalists). The present study aimed to examine (a) whether attitudes toward sexual offenders differ depending upon one's implicit theory about human nature and sexual offenders, and (b) whether implicit theories are associated with judgments made about different types of child abusers. A sample of 252 community participants was recruited. Their attitudes, implicit theories, and political orientation were assessed via self-report. One of three vignettes describing an incidence of child sexual abuse was then presented. The cases were identical except the perpetrator was either an adult male, an adult female, or a male juvenile. Participants then made judgments about the offender's deserved sentence and moral character. Entitists (across both domains) held more negative attitudes than incrementalists, although the magnitude of the difference was greatest when examining implicit theories about sexual offenders. Compared with those with an incremental theory of sexual offenders, entity theorists judged sexual offending to be more (a) indicative of the perpetrator's moral character and (b) deserving of punishment. However, scores were greater toward the adult male relative to the adult female and juvenile. The findings suggest that implicit theories about sexual offenders are domain specific. They also indicate that judgments made by those with an entity theory (about sexual offenders) are affected by whether a case is representative of a stereotypical sexual offender. Implications of the findings are discussed, along with limitations and future research. PMID- 27369243 TI - [Not Available]. PMID- 27369244 TI - [Not Available]. PMID- 27369245 TI - [Not Available]. PMID- 27369241 TI - Clinical parameters for predicting radiation-induced liver disease after intrahepatic reirradiation for hepatocellular carcinoma. AB - BACKGROUND: Few data are available on the tolerance of reirradiation in patients with hepatocellular carcinoma (HCC). This study determined the clinical parameters contributing to the development of radiation-induced liver disease (RILD). METHODS: We included 36 patients with HCC who received 2 courses of radiotherapy (RT) to the liver. Using alpha/beta = 15 for tumor and alpha/beta =8 for normal liver tissue for biologically equivalent doses in 2 Gy fractions, mean cumulative to the hepatic tumor and normal liver were 87.7 Gy15 and 31.1 Gy8, respectively. Hepatic toxicities were classified according to the Common Terminology Criteria for Adverse Events, Version 4.0. Clinical data, including liver function test results, radiological study findings, and RT parameters before and after both courses of RT were retrieved for analysis. Using multivariate analysis, logistic regression was used to identify the predictors of RILD, and Cox regression was performed to explore the prognostic factors for overall survival (OS). RESULTS: Thirteen patients (36 %) developed RILD after reirradiation. Nine of them died because of progressive liver failure without evidence of tumor progression and were categorized to have lethal RILD. A pretreatment Child-Turcotte-Pugh (CTP) score >=6 was the only predictor of RILD [odds ratio (OR): 15.83, p = 0.001] and lethal RILD [OR: 72.56, p = 0.005]. In addition, a CTP score >=6 and the presence of portal vein tumor thrombosis before reirradiation were 2 prognostic factors for OS. CONCLUSION: Despite a limited sample size, residual liver function using a preirradiation CTP score >=6 is a clinical parameter associated with an increased risk of RILD in patients requiring hepatic reirradiation. PMID- 27369246 TI - [Not Available]. PMID- 27369247 TI - [Not Available]. PMID- 27369248 TI - [Not Available]. PMID- 27369249 TI - [Not Available]. PMID- 27369250 TI - [Not Available]. PMID- 27369252 TI - [Not Available]. PMID- 27369251 TI - [Not Available]. PMID- 27369253 TI - [Not Available]. PMID- 27369254 TI - [Not Available]. PMID- 27369255 TI - [Not Available]. PMID- 27369256 TI - [Not Available]. PMID- 27369257 TI - [Not Available]. PMID- 27369258 TI - [Not Available]. PMID- 27369259 TI - [Not Available]. PMID- 27369260 TI - [Not Available]. PMID- 27369262 TI - [Not Available]. PMID- 27369261 TI - [Not Available]. PMID- 27369263 TI - [Not Available]. PMID- 27369264 TI - [Not Available]. PMID- 27369265 TI - [Not Available]. PMID- 27369266 TI - [Not Available]. PMID- 27369267 TI - [Not Available]. PMID- 27369268 TI - [Not Available]. PMID- 27369269 TI - [Not Available]. PMID- 27369270 TI - [Not Available]. PMID- 27369271 TI - [Not Available]. PMID- 27369272 TI - [Not Available]. PMID- 27369273 TI - [Not Available]. PMID- 27369274 TI - [Not Available]. PMID- 27369275 TI - [Not Available]. PMID- 27369276 TI - [Not Available]. PMID- 27369277 TI - [Not Available]. PMID- 27369278 TI - [Not Available]. PMID- 27369280 TI - Optimizing Aerosol Dispensers for Mating Disruption of Codling Moth, Cydia pomonella L. AB - Experiments were conducted in commercial apple orchards to determine if improved efficiencies in pheromone delivery may be realized by using aerosol pheromone dispensers for codling moth (CM), Cydia pomonella L., mating disruption. Specifically, we tested how reducing: pheromone concentration, period of dispenser operation, and frequency of pheromone emission from aerosol dispensers affected orientational disruption of male CM to pheromone-baited monitoring traps. Isomate(r) CM MIST formulated with 50 % less codlemone (3.5 mg/ emission) provided orientation disruption equal to the standard commercial formulation (7 mg / emission). Decreased periods of dispenser operation (3 and 6 h) and frequency of pheromone emission (30 and 60 min) provided a level of orientational disruption similar to the current standard protocol of releasing pheromone over a 12 h period on a 15 min cycle, respectively. These three modifications provide a means of substantially reducing the amount of pheromone necessary for CM disruption. The savings accompanying pheromone conservation could lead to increased adoption of CM mating disruption and, moreover, provide an opportunity for achieving higher levels of disruption by increasing dispenser densities. PMID- 27369281 TI - Volatile Organic Compounds of Decaying Piglet Cadavers Perceived by Nicrophorus vespilloides. AB - In the necrophagous burying beetle Nicrophorus vespilloides (Coleoptera: Silphidae), cadaver preference appears to depend on cadaver size and on the maturity of the beetle. We previously showed that newly emerged females with immature ovaries prefer later stages of decomposition of large cadavers. Our present aim is the determination of specific chemical compounds involved in the discrimination of cadaveric odor bouquets and the recognition of specific stages of decomposition. We used headspace samples of maggot-infested piglet cadavers at various decomposition stages and performed gas chromatography coupled with electroantennography (GC-EAD) to record 45 EAD-active compounds. Using GC coupled with mass spectrometry, we identified 13 of the EAD-active compounds. The headspace of the fresh decomposition stage was characterized mainly by high relative amounts of trimethylpyrazine. High relative amounts of dimethyl trisulfide were characteristic of bloated, post-bloating, and advanced decay stages. The advanced decay and dry remains stages were dominated by high relative amounts of phenol. Statistically, this compound had the highest impact on discrimination between the fresh decomposition stage, which is important for mature burying beetles for reproduction, and the advanced decay stage, which is nutritionally more attractive for newly emerged beetles. Phenol might, therefore, function as a key substance for newly emerged female burying beetles, so that they can locate suitable cadavers for feeding to maturation. PMID- 27369282 TI - Mating Disruption of a Carpenter Moth, Cossus insularis (Lepidoptera: Cossidae) in Apple Orchards with Synthetic Sex Pheromone, and Registration of the Pheromone as an Agrochemical. AB - Mating disruption of the carpenter moth, Cossus insularis (Staudinger) (Lepidoptera: Cossidae), with a synthetic version of its sex pheromone, a mixture of (E)-3-tetradecenyl acetate and (Z)-3-tetradecenyl acetate, was tested for three successive years in apple (Malus domestica Borkh.) orchards. Pheromone trap catches, percentage mating of tethered females and females enclosed with males in a mating cage, and tree damage were measured in both the pheromone-treated and untreated control orchards. The attraction of male moths to pheromone traps at heights of 1.5, 3, and 5 m was strongly disrupted when the pheromone dispensers were placed at 1.5 m height. Mating of tethered females placed at 1 m was completely inhibited, and the mating of tethered females at a height of 3 m was significantly reduced by the treatment in comparison to matings in an untreated control orchard. Similarly, mating of pairs of moths enclosed in mating cages was significantly reduced by the synthetic pheromone treatment in comparison to controls. The percentage of damaged trees in the pheromone-treated orchard also decreased significantly over the course of the experiment. These results suggest that mating disruption with the synthetic sex pheromone appears promising for reducing damage caused by C. insularis in apple orchards in Japan, and a commercial mating disruption product has been developed and registered. PMID- 27369284 TI - Clinical evaluation of complete solo surgery with the "ViKY(r)" robotic laparoscope manipulator. AB - BACKGROUND: Advancement in both surgical technique and medical equipment has enabled solo surgery. ViKY(r) Endoscope Positioning System (ViKY(r)) is a robotic system that remotely controls an endoscope and provides direct vision control to the surgeon. Here, we report our experience with ViKY(r)-assisted solo surgery. METHODS: We retrospectively examined 25 cases of solo surgery TAPP with ViKY(r). ViKY(r) was setup by the surgeon alone, and the setup duration was determined as the time at which the side rail was positioned and that when the endoscope was installed. For assessing the control unit, the number of false movements was counted. We compared the operative results between ViKY(r)-assisted solo surgery TAPP and the conventional method with an assistant. RESULTS: The average time to set up ViKY(r) was 7.9 min. The average number of commands for ViKY(r) during surgery was 98.3, and the average number of errors and no response of control unit was 7.9. The mean duration of surgery was 136 min for the ViKY(r) group, including the setup time, and 117 min for the conventional method. No case required an assistant during the operation. There was also no difference between the two groups with regard to postoperative complications and the rate of recurrence. CONCLUSIONS: ViKY(r) proved reliable in recognizing orders with very few failures, and the operations were performed safely and were comparable to the conventional operations with assistants. Solo surgery with ViKY(r) was beneficial in this clinical evaluation. PMID- 27369283 TI - Effects and efficacy of laparoscopic fundoplication in children with GERD: a prospective, multicenter study. AB - INTRODUCTION: Laparoscopic antireflux surgery (LARS) in children primarily aims to decrease reflux events and reduce reflux symptoms in children with therapy resistant gastroesophageal reflux disease (GERD). The aim was to objectively assess the effect and efficacy of LARS in pediatric GERD patients and to identify parameters associated with failure of LARS. METHODS: Twenty-five children with GERD [12 males, median age 6 (2-18) years] were included prospectively. Reflux specific questionnaires, stationary manometry, 24-h multichannel intraluminal impedance pH monitoring (MII-pH monitoring) and a 13C-labeled Na-octanoate breath test were used for clinical assessment before and 3 months after LARS. RESULTS: After LARS, three of 25 patients had persisting/recurrent reflux symptoms (one also had persistent pathological acid exposure on MII-pH monitoring). New-onset dysphagia was present in three patients after LARS. Total acid exposure time (AET) (8.5-0.8 %; p < 0.0001) and total number of reflux episodes (p < 0.001) significantly decreased and lower esophageal sphincter (LES) resting pressure significantly increased (10-24 mmHg, p < 0.0001) after LARS. LES relaxation, peristaltic contractions and gastric emptying time did not change. The total number of reflux episodes on MII-pH monitoring before LARS was a significant predictor for the effect of the procedure on reflux reduction (p < 0.0001). CONCLUSIONS: In children with therapy-resistant GERD, LARS significantly reduces reflux symptoms, total acid exposure time (AET) and number of acidic as well as weakly acidic reflux episodes. LES resting pressure increases after LARS, but esophageal function and gastric emptying are not affected. LARS showed better reflux reduction in children with a higher number of reflux episodes on preoperative MII-pH monitoring. PMID- 27369286 TI - Evaluation of a fully absorbable poly-4-hydroxybutyrate/absorbable barrier composite mesh in a porcine model of ventral hernia repair. AB - BACKGROUND: The objective of this study was to evaluate the mechanical and histological properties of a fully absorbable poly-4-hydroxybutyrate/absorbable barrier composite mesh (PhasixTM ST) compared to partially absorbable (VentralightTM ST), fully absorbable (PhasixTM), and biologically derived (StratticeTM) meshes in a porcine model of ventral hernia repair. METHODS: Bilateral abdominal surgical defects were created in twenty-four Yucatan pigs, repaired with intraperitoneal (PhasixTM ST, VentralightTM ST) or retromuscular (PhasixTM, StratticeTM) mesh, and evaluated at 12 and 24 weeks (n = 6 mesh/group/time point). RESULTS: Prior to implantation, StratticeTM demonstrated significantly higher (p < 0.001) strength (636.6 +/- 192.1 N) compared to VentralightTM ST (324.3 +/- 37.1 N), PhasixTM ST (206.9 +/- 11.3 N), and PhasixTM (200.6 +/- 25.2 N). At 12 and 24 weeks, mesh/repair strength was significantly greater than NAW (p < 0.01 in all cases), and no significant changes in strength were observed for any meshes between 12 and 24 weeks (p > 0.05). PhasixTM mesh/repair strength was significantly greater than StratticeTM (p < 0.001) at 12 and 24 weeks, and VentralightTM ST mesh/repair strength was significantly greater than PhasixTM ST mesh (p < 0.05) at 24 weeks. At 12 and 24 weeks, PhasixTM ST and VentralightTM ST were associated with mild inflammation and minimal-mild fibrosis/neovascularization, with no significant differences between groups. At both time points, PhasixTM was associated with minimal-mild inflammation/fibrosis and mild neovascularization. StratticeTM was associated with minimal inflammation/fibrosis, with minimal neovascularization at 12 weeks, which increased to mild by 24 weeks. StratticeTM exhibited significantly less neovascularization than PhasixTM at 12 weeks and significantly greater inflammation at 24 weeks due to remodeling. CONCLUSIONS: PhasixTM ST demonstrated mechanical and histological properties comparable to partially absorbable (VentralightTM ST) and fully resorbable (PhasixTM) meshes at 12 and 24 weeks in this model. Data also suggest that fully absorbable meshes with longer-term resorption profiles may provide improved mechanical and histological properties compared to biologically derived scaffolds. PMID- 27369285 TI - Long-term incidence of contralateral primary hernia repair following unilateral inguinal hernia repair in a cohort of 32,834 patients. AB - BACKGROUND: Asymptomatic contralateral inguinal hernias are often present during initial inguinal hernia repair. Data on long-term results and progression to symptomaticity are sparse. The purpose of this study was to assess long-term rates and risk factors for contralateral inguinal hernia repair following unilateral inguinal hernia repair. METHODS: Using New York Statewide Planning and Research Collaborative administrative data, 32,384 adults who underwent initial inguinal hernia repair during 2002-2003 in New York State and achieved 10-year follow-up were identified. ICD-9 and CPT codes were used to identify patients. Patients were followed for 10 years subsequent to their operation to assess for contralateral repair. Those who did not achieve 10-year follow-up were excluded. Risk factors were compared using descriptive univariate statistics. Significant variables were then analyzed via multivariate regression models. RESULTS: For adult patients having primary unilateral hernia repair, 3364 patients (6.73 %) had contralateral repair during the follow-up period. After excluding "loss of follow-up" patients, the contralateral repair rate was 10.8 %. Contralateral hernia repairs first occurred at a mean of 3.9 +/- 3.5 years and a median of 2.5 years after the initial surgery. Risk factors included age >45 years (OR 1.7 [1.4 2.0], p < 0.001), male gender (OR 2.2 [1.9-2.6], p < 0.0001), and white race (OR 1.6 [1.1-2.4], p < 0.001). Factors associated with decreased likelihood for repair included: congestive heart failure (OR 0.6 [0.4-0.9], p = 0.01), diabetes (OR 0.7 [0.5-0.8], p = 0.02), neurological disorders (OR 0.6 [0.4-0.9], p = 0.02), obesity (OR 0.3 [0.1-0.8], p = 0.01), and alcohol abuse (OR 0.2 [0.03 0.8], p = 0.03). CONCLUSION: The 10-year probability of necessitating a contralateral inguinal hernia repair is significant. Elderly white males were more likely to undergo repair. Those less likely to undergo repair had significant comorbid conditions, possibly due to their poor suitability for intervention. These data highlight a key benefit of the laparoscopic approach over open repairs. Based on these data, an argument for laparoscopy with routine contralateral inspection in higher-risk patients can be made. PMID- 27369287 TI - Treatment outcomes and recurrence following standard cold forceps polypectomy for diminutive polyps. AB - BACKGROUND: The recurrence rate after standard cold forceps polypectomy (CFP) of diminutive polyps of <=5 mm has not been fully determined. The aim of this study was to analyze the long-term follow-up results and recurrence rate after CFP of diminutive polyps. METHODS: We retrospectively reviewed the medical records of 884 (738 men; age 53 years) asymptomatic subjects who underwent surveillance colonoscopy after CFP of 1-2 diminutive adenomatous polyps. Cumulative recurrence at the CFP site and risk factors for recurrence were analyzed. RESULTS: Overall recurrence over 59.7 months was 17 % after CFP of 1111 diminutive polyps. The rate of definite recurrence was 4 %, and probable recurrence was 13 %. Recurrence as advanced adenoma was 0.5 % (5/1111). The cumulative probabilities of recurrence at 3, 5, and 7 years after CFP were 10.0, 16.0, and 21.1 %, respectively. Multivariate analysis revealed that polyp 4-5 mm in size and right colonic polyp were risk factors for recurrence (hazard ratio [HR] 1.37; 95 % confidence interval [CI] 1.01-1.86 and HR 1.49; 95 % CI 1.08-2.04, respectively). The recurrence rate for 10 endoscopists who performed at least 50 CFPs ranged from 11.0 to 25.2 %; the probability of recurrence in those in the top half in terms of recurrence rate was 1.6-fold higher than that of those in the bottom half (95 % CI 1.17-2.19). CONCLUSIONS: Although recurrence may develop after standard CFP of diminutive polyps, recurrence as advanced adenoma is rare. Large polyp size, right colon polyp, and endoscopist are risk factors for recurrence after standard CFP. PMID- 27369288 TI - Endoscopic-assisted selective neck dissection via small lateral neck incision for early-stage (T1-2N0M0) head and neck squamous cell carcinoma: 3-year follow-up results. AB - BACKGROUND: Primary tumors of early-stage (T1-2N0M0) head and neck squamous cell carcinoma (HNSCC) can be treated by transoral minimally invasive surgery, but the cervical lymph node lacks corresponding minimally invasive treatment. Therefore, our study was to evaluate the safety and effectiveness of endoscopic-assisted selective neck dissection (EASND) via small lateral neck incision in treatment of early-stage HNSCC. METHODS: From May 2008 to April 2012, 29 patients with early stage HNSCC were enrolled in this retrospective study. EASND via small lateral neck incision was followed by primary tumors treated by transoral endoscopy or CO2 laser microsurgery in all patients. The clinical data and follow-up results were analyzed retrospectively. RESULTS: Twenty-nine patients (male 22, female 7) were successfully treated by EASND and no case conversed to open surgery. EASND included eight cases of level I-III and 21 cases of level II-IV. The operative time was 68.4 +/- 10.3 min, and the operative bleeding was 40.8 +/- 12.4 ml. The number of lymph nodes was 19.1 +/- 4.1. There were 19 cases of T1, 10 cases of T2, 22 cases of N0, 7 cases of N1, no cases with positive margin or extracapsular spread in lymph node. Temporary sensory changes in the postauricular area occurred in two cases, both recovered within 3 months after the surgery, postoperative seromas occurred in one case. No patient showed postoperative bleeding, chylous fistula, incision infection, facial nerve injury, and accessory nerve injury. All patients were satisfied with the postoperative cosmetic results. The 3-year OS was 96.5 %, while DFS, LRFS, and DMFS were 100 %. CONCLUSION: EASND via small lateral neck incision is a feasible and safe technique with achieved short-term oncologic outcomes in early-stage (T1-2N0M0) HNSCC patients. But the long-term results of EASND on oncologic safety and functional outcomes are required to confirm by larger, randomised studies. PMID- 27369289 TI - Lodging Resistance of Japonica Rice (Oryza Sativa L.): Morphological and Anatomical Traits due to top-Dressing Nitrogen Application Rates. AB - BACKGROUND: Lodging in rice production often limits grain yield and quality by breaking or bending stems. Excessive nitrogen (N) fertilizer rates are the cause of poor lodging resistance in rice, but little is known about the effect of top dressing N application rates on the mechanical strength of japonica rice plants, especially how the anatomical structure in culms is affected by N. In this study, field experiments on two japonica rice varieties with three top-dressing N application rates, 0 kg N ha(-1) (LN), 135 kg N ha(-1) (MN), and 270 kg N ha(-1) (HN) as urea, were conducted. Wuyunjing23, a lodging-resistant japonica rice cultivar and W3668, a lodging-susceptible japonica rice cultivar were used. The lodging index, breaking strength, morphological and anatomical traits in culms were measured in this study. RESULTS: The visual lodging rate in japonica rice differed remarkably between genotypes and top-dressing N treatments. The higher lodging index of rice plants was primarily attributed to the weak breaking strength of the lower internodes. The longer elongated basal internodes were responsible for higher plant height and a higher lodging index. Correlation analysis showed that breaking strength was significantly and positively correlated with the thickness of the mechanical tissue but was significantly and negatively correlated with the inner diameter of the major axis (b2). With increasing top-dressing N rates, the sclerenchyma cells of the mechanical tissues and the vascular bundles of the Wuyunjing23 cultivar varied little. The plant height, inner diameter of the minor axis (a2) and b2 increased significantly, but the area of the large vascular bundle (ALVB) and the area of the small vascular bundle (ASVB) decreased significantly and resulted in lower stem strength and a higher lodging index under higher top-dressing N conditions. The culm diameter of the W3668 cultivar increased slightly with no significant difference, and the sclerenchyma cells in the mechanical tissues and vascular bundles showed deficient lignifications under high top-dressing N conditions. Moreover, the ALVB and the ASVB decreased significantly, while the area of air chambers (AAC) increased rapidly. CONCLUSIONS: An improvement in the lodging resistance of japonica rice plants could be achieved by reducing the length of the lower internodes, decreasing the inner culm diameter and developing a thicker mechanical tissue. Top-dressing N application increased the plant height and inner culm diameter and decreased the ALVB and the ASVB of the Wuyunjing23 cultivar and caused deficient lignified sclerenchyma cells, lowered the ALVB and the ASVB, and increased the AAC of the W3668 cultivar resulting in weaker stem strength and a higher lodging index. PMID- 27369290 TI - New tools in cytometry. AB - Cytometry aims to analyze cells, of any type, using dedicated instruments. The quantitative aspect makes flow cytometry (FCM) a good complementary tool for morphology. Most of the identification tools are based on immunostaining of cell structure details and more and more tools are available in terms of specificities and labels. FCM is under exponential development thanks to technical, immunological and data analysis progresses. Actual generations are now routinely using 6 to 10 simultaneous immuno-labeling on 20 to 100,000 cells, at high speed and short sample preparation and can easily detect rare events at frequency below 10-4 cells. Data interpretation is complex and requires expertise. Mathematical tools are available to support analysis and classification of cells based. Cells from tissues can also be analyzed by FCM after mechanical and or enzymatic separation, but in situ cells can also be analyzed with the help of cytometry. Very new instruments bring spectral analysis, image in flow and mass spectrometry. Medical applications are very broad, notably in hemopathies, immunology, solid tumors, but also microbiology, toxicology, drug discovery, food and environmental industry. But, the limit of FCM is its dependence on operator from sample preparation, instrument settings up to data analysis and a strong effort is now under progress for standardization and constitution of international data bank for references and education. PMID- 27369291 TI - Treatment Strategy for Persistent Sciatic Artery and Novel Classification Reflecting Anatomic Status. AB - BACKGROUND: Persistent sciatic artery (PSA) is a relatively rare congenital variant of the lower limb vasculature and can have highly variable clinical presentations. The purpose of this study was to analyze the relationship between PSA anatomy and clinical presentation, and to suggest an optimal management strategy. METHODS: Between 2001 and 2014, 24 PSAs in 19 patients were diagnosed by computed tomography and referred to the vascular surgery department. Patient demographics, types of PSA and femoral artery, aneurysmal changes, symptoms, and treatment methods were assessed. Additionally, all English literature from 1964 to 2014 was reviewed and compared using the PubMed database (224 PSAs in 171 patients). RESULTS: PSA was diagnosed in 10 men (52.6%) and nine women (47.4%). PSAs were bilateral in five patients (26.3%) and symptomatic in 12 patients, while in seven patients PSA was found incidentally. According to the Pillet Gauffre classification, Type 2a was the most common variant (n = 15/24, 62.5%), with unclassifiable types in two limbs. Compared with cases in the literature, the PSA occlusion rate in this study was higher (n = 10/24, 41.7% vs. n = 54/224, 27.5%), but aneurysm incidence was higher in the literature cases (n = 5/24, 20.8% vs. n = 112/224; 50.7%). In this study, 16 limbs (66.6%) were treated conservatively, and six limbs were treated by open surgery, including four bypasses, one amputation, and one thrombo-embolectomy. Endovascular coil embolization was performed in one limb, and a hybrid procedure with stent graft was performed in one limb with PSA aneurysm. Based on the present series and the literature review, a new classification system and treatment option is proposed according to the anatomic status and the presence of aneurysm. According to the new classification, class III was the most common in both the present study (18/24; 75%) and the literature review, and the presence of aneurysm was the most important determinant of surgical treatment. CONCLUSIONS: The new classification system is simple and provides guidance for management. Limb anatomy of the femoral artery system and the presence of PSA aneurysm should be considered when selecting the optimal treatment. The risk of embolism from the presence of aneurysm is an important factor for treatment, and bypass surgery is mostly required in classes III and IV. PMID- 27369292 TI - COPART Risk Score, Endothelial Dysfunction, and Arterial Hypertension are Independent Risk Factors for Mortality in Claudicants. AB - OBJECTIVE: The COPART risk score consists of six variables to assess the prognosis of PAOD patients. The flow mediated dilation (FMD) quantifies endothelial function. The aim of this study was to evaluate the mortality prediction of these two variables in a long-term observation of claudicants. METHODS: 184 consecutive claudicants were included in a prospective observational study over a median observation period of 7.9 (IQR 7.2-8.7) years. The endothelial function was assessed on the day of study inclusion using brachial FMD. RESULTS: Three groups were assigned according to the COPART risk score: low risk (LR), n = 72 (39%); medium risk (MR), n = 59 (32%); and high risk (HR), n = 53 (29%). Overall survival rates differed among COPART risk score groups (p < .001, 5 year survival: LR group 83% [95% CI 74-92%]; MR group 73% [95% CI 62 84%]; HR group 57% [95% CI 43-70%]). Survivors had a significantly better median FMD than non-survivors (4.1% [IQR 1.2-6.4] vs. 1.3% [IQR 0.0-4.2]; p < .001). Also the FMD differed significantly among the three COPART risk groups (LR 4.0% [IQR 1.2-6.3], MR 2.3% [IQR 0.0-6.3], HR 1.7% [IQR 0.0-3.6]; p = .033). Finally, independent predictors for disease specific survival were COPART risk score (p = .033; MR group [HR 1.6], 95% CI 0.7-3.6; HR group [HR 2.7], 95% CI 1.2-5.8), FMD (p = .004; FMD <=2.5 vs. >2.5, HR 2.6, 95% CI 1.4-4.9), and arterial hypertension (p = .039; HR 3.5, 95% CI 1.1-11.3). CONCLUSIONS: COPART risk score, FMD, and arterial hypertension are independent long-term mortality predictors in this group of claudicants. The best mortality assessment is provided by including all three predictors. PMID- 27369293 TI - Risk of Recurrent Stroke in Patients with Symptomatic Mild (20-49% NASCET) Carotid Artery Stenosis. AB - OBJECTIVE: The objective of this study was to evaluate the risk of recurrent ischaemic stroke in patients with ultrasound assessed symptomatic mild carotid artery stenosis (20-49% NASCET) treated solely with modern medical treatment. METHOD: This was a retrospective, observational register cohort study. Three groups of patients were recruited from a database of all carotid Doppler ultrasound examinations performed in the Gothenburg region between 2004 and 2009. Patients with symptomatic mild carotid artery stenosis (n = 162) were compared with patients with asymptomatic carotid artery stenosis (n = 301) of equal degree and a group of patients with surgically (CEA) treated symptomatic moderate or severe carotid artery stenosis (n = 220). Kaplan-Meier estimates and Cox proportional hazard models were used to compare the primary outcome (ipsilateral ischaemic stroke) between groups. RESULTS: After a 3 year follow up, the cumulative incidence of recurrent ipsilateral stroke in patients with symptomatic mild carotid artery stenosis was 7.4%. Patients with symptomatic mild carotid artery stenosis had a substantially increased risk of recurrent ipsilateral stroke compared with asymptomatic patients with equal degree of stenosis (HR 5.5. 95% CI 1.8-17.1; p = .003) as also compared with patients with CEA treated symptomatic moderate or severe stenosis (HR 7.8. 95% CI 1.62-37.8; p = .011). CONCLUSIONS: The present study on patients with symptomatic mild carotid artery stenosis, as determined by Doppler ultrasound, shows that there is still a substantial risk of recurrent stroke in this group. PMID- 27369294 TI - Computerized tomography attenuation values can be used to differentiate hydronephrosis from pyonephrosis. AB - PURPOSE: To determine the diagnostic value of computerized tomography (CT) in differentiating pyonephrosis from hydronephrosis on the basis of attenuation values (Hounsfield unit-HU). METHODS: Data of the patients with grades 1-3 hydronephrosis on abdominopelvic CT, who underwent nephrostomy tube placement for decompression of the collecting system, were retrospectively analyzed. Patient demographics and CT findings were recorded along with the first access urine culture results. Three physicians calculated the surface areas and the attenuation values of the dilated collecting systems using the system software. Mean HU of pyonephrosis and hydronephrosis cases was compared. RESULTS: A total of 105 patients with the mean age of 47.7 +/- 15.5 (range 20-80) were included. The interclass correlation coefficient of three physicians was 0.981 for HU measurement and 0.999 for calculation of collecting system surface area. Of the patients, 47 (44.8 %) had pyonephrosis. Mean surface areas of the collecting system were similar in patients with pyonephrosis and hydronephrosis (1481.13 +/- 1562.94 vs. 1612.94 +/- 2261.4 mm2, p = 0.735). Urine cultures were positive in all patients with pyonephrosis, whereas 12.7 % of hydronephrosis cases had bacterial in first access urine culture. The HU of the patients with pyonephrosis was significantly higher that that of patients with hydronephrosis (13.51 +/- 13.29 vs. 4.67 +/- 5.37, p = 0.0001). Having a HU of 9.21 or over diagnosed pyonephrosis accurately with 65.96 % sensitivity and 87.93 % specificity. CONCLUSION: Measuring attenuation values of the collecting system may be useful to differentiate pyonephrosis from hydronephrosis. Diagnosing pyonephrosis accurately may avoid septic complications. PMID- 27369295 TI - The Role of Ion Channels to Regulate Airway Ciliary Beat Frequency During Allergic Inflammation. AB - Overproduction of mucus is a hallmark of asthma. The aim of this study was to identify potentially effective therapies for removing excess mucus. The role of voltage-gated (Kir 6.1, KCa 1.1) and store-operated ion channels (SOC, CRAC) in respiratory cilia, relating to the tracheal ciliary beat frequency (CBF), was compared under the physiological and allergic airway conditions. Ex vivo experiments were designed to test the local effects of Kir 6.1, KCa 1.1 and CRAC ion channel modulators in a concentration-dependent manner on the CBF. Cilia, obtained with the brushing method, were monitored by a high-speed video camera and analyzed with ciliary analysis software. In natural conditions, a Kir 6.1 opener accelerated CBF, while CRAC blocker slowed it in a concentration-dependent manner. In allergic inflammation, the effect of Kir 6.1 opener was insignificant, with a tendency to decrease CBF. A cilio-inhibitory effect of a CRAC blocker, while gently reduced by allergic inflammation, remained significant. A KCa 1.1 opener turned out to significantly enhance the CBF under the allergic OVA sensitized conditions. We conclude that optimally attuned concentration of KCa 1.1 openers or special types of bimodal SOC channel blockers, potentially given by inhalation, might benefit asthma. PMID- 27369296 TI - A Social Media mHealth Solution to Address the Needs of Dengue Prevention and Management in Sri Lanka. AB - BACKGROUND: Sri Lanka has witnessed a series of dengue epidemics over the past five years, with the western province, home to the political capital of Colombo, bearing more than half of the dengue burden. Existing dengue monitoring prevention programs are exhausted as public health inspectors (PHIs) cope with increasing workloads and paper-based modes of surveillance and education, characterizing a reactive system unable to cope with the enormity of the problem. On the other hand, the unprecedented proliferation and affordability of mobile phones since 2009 and a supportive political climate have thus far remained unexploited for the use of mobile-based interventions for dengue management. OBJECTIVE: To conduct a needs assessment of PHIs in Colombo with respect to their dengue-related tasks and develop a new mobile-based system to address these needs while strengthening existing systems. METHODS: One-on-one in-depth interviews were conducted with 29 PHIs to a) gain a nuanced, in-depth understanding of the current state of surveillance practices, b) understand the logistical, technological and social challenges they confront, and c) identify opportunities for mobile-based interventions. Quantitative analysis included simple descriptive statistics while qualitative analysis comprised textual analysis of 209 pages of transcripts (or nearly 600 minutes of conversations) using grounded theory approaches. RESULTS: Current paper-based data collection practices for dengue surveillance involved a circuitous, time consuming process that could take between 7-10 days to officially report and record a single case. PHIs confronted challenges in terms of unreliable, standalone GIS devices, delays in registering mosquito breeding sites and lack of engagement from communities while delivering dengue education. These findings, in concert with a high motivation to use mobile based systems, informed the development of Mo-Buzz, a mobile-based system that integrates three components - digitized surveillance, dynamic disease mapping and digitized dengue education - on a common platform. The system was developed through an iterative, evolutionary, collaborative process, consistent with the Spiral model of software development and is currently being used by all 55 PHIs in the CMC system. CONCLUSIONS: Given the entrenched nature of existing paper based systems in PHIs' work habits, we expect a gradual adoption curve for Mo Buzz in the future. Equally, we expect variable adoption of the system with respect to its specific components, and specific PHI sub-groups (younger versus older). The Mo-Buzz intervention is a response to multiple calls by the global mHealth community for collaborations in the area of mobile interventions for global health. Our experience revealed that the benefits of this paradigm lies in alleviating country-specific public health challenges through a commonly shared understanding of cultural mores, and sharing of knowledge and technologies. We call upon future researchers to further dissect the applicability of the Spiral Model of software development to mHealth interventions and contribute to the mHealth evidence debate from theoretical and applied perspectives. PMID- 27369297 TI - Determining False Positive Rates of Leukocyte Esterase Reagent Strip When Used as a Detection Tool for Joint Infection. AB - BACKGROUND: Use of leukocyte esterase (LE) testing of synovial fluid as an adjunct to the infection workup in total joint arthroplasty patients has been advocated. The purpose of this study was to determine the false positive rate of this test. METHODS: Two hundred patients with the diagnosis of degenerative osteoarthritis undergoing a total knee arthroplasty were identified for this study. The knee joint was aspirated under sterile conditions before performing the total knee arthroplasty. The fluid was analyzed with an LE reagent strip. RESULTS: There were 27 bloody and 17 dry aspirations. One hundred forty-nine patients produced an aspiration that allowed for LE testing. There was 1 positive LE result. The specificity of the LE test was found to be 99.3%. CONCLUSION: These data suggest the LE strip as a part of the workup for infection in a native knee should yield few false positive results. PMID- 27369298 TI - Are We Subluxating Knees in Total Knee Arthroplasty? A Cadaveric Investigation. AB - BACKGROUND: In comparison to coronal, sagittal, and rotational alignment, translational alignment parameters have been widely neglected in total knee arthroplasty (TKA) so far. As there is a certain variable range of possible component placement in mediolateral, ventrodorsal, and proximodistal direction, we hypothesized that relative positions between the femoral and tibial bones are changed after TKA, resulting in a subluxation of knees. METHODS: In 10 knees of Thiel-embalmed whole body cadavers, the relative position between the femur and the tibia during passive flexion was measured before and after TKA by means of a navigational device. RESULTS: After TKA, in extension, femoral bones in average shifted 5.3 mm (standard deviation [SD] = 4.0, P = .002) laterally and 2.4 mm (SD = 3.1, P = .038) proximally in extension which, however, decreased throughout flexion. Furthermore, the ventrodorsal femoral position was altered, resulting in a slight relative dorsal shift (2.6 mm, SD = 4.5, P = .099) in extension, which continuously changed into a ventral shift (2.6 mm, SD = 4.3, P = .087) during flexion. CONCLUSION: The present investigation reveals changed translational parameters between the tibia and the femur after TKA. The resulting subluxation of the knee may be responsible for changed kinematic patterns. These changes in tibofemoral position should be considered in future biomechanical studies. Main reasons for this effect might be a noncentral placement of tibial and femoral implants in relation to the proximal tibial and distal femoral anatomy, obscured intraoperative articular geometry, symmetric implants, and operative techniques. Smaller steps between different component sizes, asymmetric tibial implant design, or individual (anatomic) implants could help to minimize subluxation in TKA. PMID- 27369299 TI - Polyethylene Wear Associated With 26- and 32-mm Heads in Total Hip Arthroplasty: A Multicenter, Prospective Study. AB - BACKGROUND: Although there were many clinical studies of highly cross-linked polyethylene (XLPE) wear among different femoral head diameters, few referred to thickness of XLPE in case larger femoral heads were used because smaller sockets were frequently used for Asian population. METHODS: This prospective study included 240 hips that underwent primary total hip arthroplasty using XLPE combined with 26-mm (group S) or 32-mm (group L) cobalt-chromium head with maximum follow-up of 10 years. We measured 3-dimensional (3-D) linear penetration rate of XLPE among same implant design groups except head diameter and estimated the validity of thinner XLPE. RESULTS: Our study demonstrated comparable 3-D linear penetration rates, which were 0.06 +/- 0.07 mm/y for group S and 0.03 +/- 0.02 mm/y for group L at 10 years after surgery and penetration rates seemed to be almost constant with no significant difference after 3 years. Minimum liner thickness (5.3 mm for 48-mm socket in combination with 32-mm femoral head) and the second thinnest XLPE (6.3 mm in case of socket from 50 mm to 54 mm combined with 32-mm femoral head) was distributed in 25% and 72% with group L, respectively, and there were no significant differences in penetration rates between 5.3-mm- and 6.3-mm-thickness groups. CONCLUSION: Our study suggested that whether to select 26- or 32-mm diameters of femoral head does not affect XLPE wear in combination with this type of articulation. PMID- 27369300 TI - Direct Anterior Approach for Total Hip Arthroplasty in the Lateral Decubitus Position: Our Experiences and Early Results. AB - BACKGROUND: The direct anterior approach (DAA) for total hip arthroplasty (THA) is typically performed in the supine position using a specially designed operating room table, which makes this approach more accessible to orthopedic surgeons. We attempted to perform this procedure in the lateral decubitus position on an ordinary operation table to avoid dependence on a special operating room table. There is an obvious absence of literature regarding this subject. METHODS: A total of 248 patients (295 hips) were recruited for primary THAs from July 1, 2014 to December 31, 2014. In total, 126 hips (42.7%) underwent THAs using the DAA in the lateral decubitus position. The technical feasibility and early results were evaluated. RESULTS: The orientation of the acetabular component was 16.5 degrees +/- 4.9 degrees anteversion and 43.3 degrees +/- 3.5 degrees abduction. Intraoperative proximal femoral fracture occurred in one hip. The superficial wound complications occurred in 2 hips and the hematoma in one hip while in hospital. The lateral femoral cutaneous nerve injury was noted in 43 hips. The early dislocation occurred in 2 hips. Heterotopic ossification was Brooker class I in 5 hips and class II in 1 hip. No aseptic loosening, postoperative periprosthetic fracture, and deep infection occurred in our series. CONCLUSION: The DAA for THA in the lateral decubitus position may be a valuable alternative if the DAA in the supine position is difficult to implement owing to absence of a special operating room table. This technique also seems to provide satisfactory clinical and radiographic outcomes with an acceptable complication in our early follow-up. PMID- 27369301 TI - Obesity and Venous Thromboembolism in Total Knee Arthroplasty Patients in an Asian Population. AB - BACKGROUND: Venous thromboembolism (VTE) is a known complication of total knee arthroplasty (TKA). In addition, obesity has been implicated as a risk factor and justification for chemoprophylaxis for VTE. We wanted to review the prevalence of VTE among our patients and evaluate the incidence rates of VTE among nonobese and obese patients. METHODS: We reviewed 894 patients who underwent elective unilateral total knee arthroplasty by a single surgeon from March 2003 to November 2014 in our center. Any patients with clinically significant symptoms or signs of VTE such as deep venous thrombosis (DVT) or pulmonary embolism (PE) were diagnosed radiologically. The patient demographics analyzed included age, gender, body mass index, the number of comorbid diseases, and a history of hyperlipidemia. RESULTS: We found the incidence of VTE of 0.67% in our patients (6 patients of 894). Four of the 6 patients (66.7%) who developed DVT and PE belonged to nonobese group. The frequency of VTE in nonobese patients was 0.65% and 0.73% in the obese patients. There were no significant differences in age, number of comorbidities, and a history of hyperlipidemia between those who developed DVT and PE and those who did not. CONCLUSION: With the low prevalence of VTE among our study population, including patients with obesity, advanced age, multiple comorbidities, or hyperlipidemia, the practice of routine chemoprophylaxis should be reviewed. PMID- 27369302 TI - Accuracy of Balancing at Total Knee Surgery Using an Instrumented Tibial Trial. AB - BACKGROUND: Balancing is an important part of a total knee procedure, and in recent years, more emphasis has been given to quantifying the process. METHODS: During 101 total knee surgeries, initial bone cuts were made using navigation. Lateral and medial contact forces were determined throughout flexion using an instrumented tibial trial. Balancing was defined as a ratio of the medial and total force, the target being 0.5 (equal lateral and medial forces). Based on the initial values, surgical corrections were selected to achieve balancing. The most common corrections were soft tissue releases (63 incidences), including MCL, posterolateral corner, posteromedial corner, and changing tibial insert thicknesses (34 incidences). RESULTS: After final balancing, the mean ratio was 0.52 +/- 0.14, between 0.35 and 0.65 being achieved in 80% of cases. In 84% of cases, only 0-2 corrections were required. The average total force on the condyles was 215 +/- 86 N. CONCLUSION: Our study provides data to surgeons on the results to expect when balancing a knee, which can enhance both accuracy and consistency of the procedure. PMID- 27369303 TI - Variable Reporting by Authors Presenting Arthroplasty Research at Multiple Annual Conferences. AB - BACKGROUND: Prior studies have demonstrated discrepancies in financial conflict of interest (COI) disclosure among authors presenting research at multiple spine and sports medicine conferences. The purpose of this study was to quantify the variability of self-reported financial disclosures of individual authors presenting at multiple arthroplasty conferences during the same year. METHODS: The author disclosure information published for the 2012 annual meetings of the American Academy of Orthopaedic Surgeons (AAOS), American Association of Hip and Knee Surgeons, the Hip Society, and the Knee Society were compiled. We tabulated the author disclosures, the number of companies/entities represented, and the types of disclosures reported. The disclosures made by authors presenting at more than one meeting were then compared for discrepancies. RESULTS: Of the 209 authors who presented at both the AAOS and American Association of Hip and Knee Surgeons meetings, 79 (37.79%) demonstrated discrepancies in their disclosures with 7 (8.8%) reporting no disclosures to the AAOS. Of the 84 authors who presented at both the AAOS and Hip Society meetings, 1 (1.19%) had discrepancies in their disclosures. Of the 52 authors who presented at both the AAOS and Knee Society meetings, 2 (3.84%) had discrepancies in their disclosures. CONCLUSION: There is variability in reported financial COIs by authors presenting at multiple arthroplasty conferences within the same year. Further work is warranted to improve transparency of COI disclosures among arthroplasty surgeons presenting research at national meetings. PMID- 27369304 TI - Accuracy of Computed Tomography-Based Navigation-Assisted Total Knee Arthroplasty: Outlier Analysis. AB - BACKGROUND: Achieving neutral limb alignment during total knee arthroplasty (TKA) has been identified as a potential factor in long-term prosthesis survival. This study aimed to analyze the accuracy of component orientation and postoperative alignment of the leg after computed tomography (CT)-based navigation-assisted TKA, compare these parameters with those of a conventional technique, and analyze differences in the data of outliers. METHODS: We retrospectively compared the alignment of 130 TKAs performed with a CT-based navigation system with that of 67 arthroplasties done with a conventional system. The knee joints were evaluated using radiographs. RESULTS: Mean hip-knee-ankle (HKA) angle, frontal femoral component angle, and frontal tibial component angle were 180.7 degrees , 88.8 degrees , and 90.6 degrees , respectively, for the navigation-assisted arthroplasties and 181.1 degrees , 88.7 degrees , and 90.2 degrees , respectively, for the conventional arthroplasties. All preoperative leg axes of 10 outliers in the navigation group were >193 degrees , whereas the data of 17 outliers in the conventional group were scattered. CONCLUSION: This study demonstrates significant improvements in component positioning with the CT-based navigation system. Furthermore, when analyzing cases with preoperative HKA angles <=192 degrees , no outliers were found in the navigation group, indicating high alignment accuracy. However, in cases with preoperative HKA angles >=193 degrees , outliers were found in both groups, and no significant difference between the groups was observed (P = .08). Detailed analysis of the outlier cases in the navigation group revealed that the femoral component was placed in the varus position. These findings indicate that the varus knee is an important factor influencing accurate positioning of the femoral component and the postoperative leg axis. PMID- 27369310 TI - Free prescribing app. AB - NHS health and social care professionals with smartphones (Android and iOS) can download a free National Institute for Health and Clinical Excellence and British National Formulary app to gain access to the latest up-to-date prescribing information. PMID- 27369311 TI - Hydration campaign. AB - Inadequate hydration affects about one in five people admitted to hospital as an emergency; many are older people. PMID- 27369312 TI - Rabies training module. AB - An online training module for healthcare staff who may have contact with people exposed to rabies has been developed by the Health Protection Agency (HPA). The module provides the knowledge and tools necessary to carry out structured risk assessments of potential rabies exposures, and how to request post-exposure prophylaxis (PEP) from local stockholders. PMID- 27369313 TI - Report on medicines safety. AB - A report that recommends improvements to the transfer of information about medicines when patients move between care settings has been published by the Royal Pharmaceutical Society (RPS). PMID- 27369315 TI - Out for consultation. AB - Objectives to make the NHS a more 'patient-centred, independent, transparent and outcomes focused' service are set out in a draft mandate from the NHS Commissioning Board. PMID- 27369314 TI - Effective leadership. AB - The importance of effective leadership to patient safety is discussed in one of a series of 'thought papers' commissioned by the Health Foundation to stimulate discussion and reflection. PMID- 27369316 TI - Associations of reading posture, gaze angle and reading distance with myopia and myopic progression. AB - PURPOSE: To study the associations of habitual reading posture, gaze angle in reading and reading distance with myopia and changes in myopia among myopic children. METHODS: A total of 240 myopic schoolchildren (mean age 10.9 years), with no previous spectacles, were recruited during 1983-1984 to a randomized 3 year clinical trial of bifocal treatment of myopia. Three annual examinations with subjective cycloplegic refraction were conducted for 237-238 subjects. A further examination was conducted at the mean age of 23.2 years for 178 subjects. Habitual reading posture was elicited by questionnaire at study outset. Reading distance was measured with a Clement Clark accommodometer and gaze angle with an angle scale at baseline and all three annual follow-ups. Height was measured by a school nurse. The connections between the variables were studied with the standard statistical methods. RESULTS: Higher myopia was connected with shorter reading distance among girls at follow-ups 2 and 3, but not at the other examinations. The correlation of spherical equivalent with height was non significant at each follow-up. Myopic progression across the whole follow-up was highest among those who read sitting down at baseline (-3.58 +/- 1.75 D) and lowest among those who read face up lying down (-2.35 +/- 1.53 D) (p = 0.021). Reading with eyes at a more downward angle was slightly connected with greater myopic progression (r = -0.166, p = 0.028). CONCLUSIONS: Reading in a sitting posture at myopia onset predicted the greatest myopic progression to adulthood and reading face up on one's back the lowest. Reading with eyes on turned more downwards was slightly connected with greater myopic progression. PMID- 27369318 TI - Editorial Commentary: Probe-to-Bone Test for Detecting Diabetic Foot Osteomyelitis: Rapid, Safe, and Accurate-but for Which Patients? PMID- 27369317 TI - Matrix- and plasma-derived peptides promote tissue-specific injury responses and wound healing in diabetic swine. AB - BACKGROUND: Non-healing wounds are a major global health concern and account for the majority of non-traumatic limb amputations worldwide. However, compared to standard care practices, few advanced therapeutics effectively resolve these injuries stemming from cardiovascular disease, aging, and diabetes-related vasculopathies. While matrix turnover is disrupted in these injuries, debriding enzymes may promote healing by releasing matrix fragments that induce cell migration, proliferation, and morphogenesis, and plasma products may also stimulate these processes. Thus, we created matrix- and plasma-derived peptides, Comb1 and UN3, which induce cellular injury responses in vitro, and accelerate healing in rodent models of non-healing wounds. However, the effects of these peptides in non-healing wounds in diabetes are not known. Here, we interrogated whether these peptides stimulate healing in a diabetic porcine model highly reminiscent of human healing impairments in type 1 and type 2-diabetes. METHODS: After 3-6 weeks of streptozotocin-induced diabetes, full-thickness wounds were surgically created on the backs of adult female Yorkshire swine under general anesthesia. Comb1 and UN3 peptides or sterile saline (negative control) were administered to wounds daily for 3-7 days. Following sacrifice, wound tissues were harvested, and quantitative histological and immunohistochemical analyses were performed for wound closure, angiogenesis and granulation tissue deposition, along with quantitative molecular analyses of factors critical for angiogenesis, epithelialization, and dermal matrix remodeling. RESULTS: Comb1 and UN3 significantly increase re-epithelialization and angiogenesis in diabetic porcine wounds, compared to saline-treated controls. Additionally, fluorescein-conjugated Comb1 labels keratinocytes, fibroblasts, and vascular endothelial cells in porcine wounds, and Far western blotting reveals these cell populations express multiple fluorescein-Comb1-interacting proteins in vitro. Further, peptide treatment increases mRNA expression of several pro-angiogenic, epithelializing, and matrix-remodeling factors, importantly including balanced inductions in matrix metalloproteinase-2, -9, and tissue inhibitor of metalloproteinases-1, lending further insight into their mechanisms. CONCLUSIONS: Comb1 and UN3 stimulate wound resolution in diabetic Yorkshire swine through upregulation of multiple reparative growth factors and cytokines, especially matrix metalloproteinases and inhibitors that may aid in reversing the proteolytic imbalance characteristic of chronically inflamed non-healing wounds. Together, these peptides should have great therapeutic potential for all patients in need of healing, regardless of injury etiology. PMID- 27369319 TI - Gender Differences in Statin Prescription Rate Among Patients Living With HIV and Hepatitis C Virus. PMID- 27369320 TI - Influenza Vaccine Effectiveness Against Antigenically Drifted Influenza Higher Than Expected in Hospitalized Adults: 2014-2015. AB - BACKGROUND: The 2014-2015 influenza season was severe, with circulating influenza A (H3N2) viruses that were antigenically drifted from the vaccine virus. Reported vaccine effectiveness (VE) estimates from ambulatory care settings were markedly decreased. METHODS: Adults, hospitalized at 2 hospitals in southeast Michigan for acute respiratory illnesses, defined by admission diagnoses, of <=10 days duration were prospectively enrolled. Throat and nasal swab specimens were collected, combined, and tested for influenza by real-time reverse transcription polymerase chain reaction. VE was estimated by comparing the vaccination status of those testing positive for influenza with those testing negative in logistic regression models adjusted for age, sex, hospital, calendar time, time from illness onset to specimen collection, frailty score, and Charlson comorbidity index (CCI). RESULTS: Among 624 patients included in the analysis, 421 (68%) were vaccinated, 337 (54%) were female, 220 (35%) were age >=65 years, and 92% had CCI > 0, indicating >=1 comorbid conditions. Ninety-eight (16%) patients tested positive for influenza A (H3N2); among 60 (61%) A (H3N2) viruses tested by pyrosequencing, 53 (88%) belonged to the drifted 3C.2a genetic group. Adjusted VE was 43% (95% confidence interval [CI], 4-67) against influenza A (H3N2); 40% (95% CI, -13 to 68) for those <65 years, and 48% (95% CI, -33 to 80) for those >=65 years. Sensitivity analyses largely supported these estimates. CONCLUSIONS: VE estimates appeared higher than reports from similar studies in ambulatory care settings, suggesting that the 2014-2015 vaccine may have been more effective in preventing severe illness requiring hospitalization. PMID- 27369322 TI - Treatment of Hepatitis C Virus in HIV-Coinfected Individuals in Real-world Clinical Settings: Results From 2 Large HIV Care Clinics. PMID- 27369321 TI - Diagnostic Accuracy of Probe to Bone to Detect Osteomyelitis in the Diabetic Foot: A Systematic Review. AB - The probe-to-bone (PTB) test is a commonly used clinical test for osteomyelitis (OM), but its utility has been questioned in clinical settings where the prevalence of OM is low. This article aims to systematically review the accuracy of the PTB test to diagnose diabetic foot OM. We searched Ovid Medline and Scopus databases for studies using the keywords "probe to bone," "osteomyelitis," and "diabetic foot" from 1946 to May 2015. We summarized characteristics of the included studies and pooled the accuracy numbers using a bivariate random-effects model. Seven studies met our inclusion criteria. Pooled sensitivity and specificity for the PTB test was 0.87 (95% confidence interval [CI], .75-.93) and 0.83 (95% CI, .65-.93), respectively. We conclude that the PTB test can accurately rule in diabetic foot OM in the high-risk patients and rule out OM in low-risk patients. PMID- 27369323 TI - Effects of norepinephrine on spontaneous firing activity of cerebellar Purkinje cells in vivo in mice. AB - Norepinephrine (NE), from the locus coeruleus (LC), has been supported to affect GABAergic system and parallel fiber (PF)-Purkinje cell (PC) synaptic transmission via adrenoceptor in cerebellum cortex. However, the effects of NE on the spontaneous spike activity of cerebellar PCs in living mouse have not yet been fully understood. We here examined the effects of NE on the spontaneous activity of PC in urethane-anesthetized mice by electrophysiological and pharmacological methods. Cerebellar surface application of NE (2.5-25MUM) reduced the PC simple spike (SS) firing rate in a dose-dependent manner. The half-inhibitory concentration (IC50) was 5.97MUM. In contrast, NE significantly increased the spontaneous firing rate of molecular layer interneuron (MLI). Application of GABAA receptor antagonist, gabazine (SR95531, 20MUM) not only blocked the NE induced inhibition of PC SS firing but also revealed NE-induced excitation of cerebellar PC. Blocking AMPA receptors activity enhanced NE-induced inhibition of PC spontaneous activity. Moreover, the effects of NE on PC spontaneous activity were abolished by simultaneously blocking GABAA and AMPA receptors activity. These results indicated that NE bidirectional modulated the spontaneous activity of PCs via enhancing both inhibitory inputs from MLIs and excitatory inputs of parallel fibers, but NE-induced enhance of inhibitory inputs overwhelmed the excitatory inputs under in vivo conditions. PMID- 27369324 TI - Abuse potential and dopaminergic effect of alkyl nitrites. AB - The abuse of alkyl nitrites is common among adolescents and young adults worldwide. However, the information regarding the effects of alkyl nitrites on the central nervous system and the associated psychological abuse potential is scarce. The abuse potential of 3 representative alkyl nitrites - isobutyl nitrite, isoamyl nitrite, and butyl nitrite - was evaluated in mice using conditioned place preference tests with an unbiased method. The dopamine levels released by synaptosomes extracted from the striatal region were measured using high performance liquid chromatography. Mice treated with the test substances (50mg/kg, i.p.) exhibited a significantly increased drug-paired place preference. Moreover, greater levels of dopamine were released by striatal region synaptosomes in response to isobutyl nitrite treatment in mice. Thus, our findings suggest that alkyl nitrites could lead to psychological dependence and dopaminergic effects. Furthermore, these results provide scientific evidence to support the regulation of alkyl nitrites as psychoactive substances in the future. PMID- 27369325 TI - Working memory capacity differentially influences responses to tDCS and HD-tDCS in a retro-cue task. AB - There is growing interest in non-invasive brain stimulation techniques. A drawback is that the relationship between stimulation and cognitive outcomes for various tasks are unknown. Transcranial direct current stimulation (tDCS) provides diffuse current spread, whereas high-definition tDCS (HD-tDCS) provides more targeted current. The direction of behavioral effects after tDCS can be difficult to predict in cognitive realms such as attention and working memory (WM). Previously, we showed that in low and high WM capacity groups tDCS modulates performance in nearly equal and opposite directions on a change detection task, with improvement for the high capacity participants alone. Here, we used the retro-cue paradigm to test attentional shifting among items in WM to investigate whether WM capacity (WMC) predicted different behavioral consequences during anodal tDCS or HD-tDCS to posterior parietal cortex (PPC). In two experiments, with 24 participants each, we used different stimulus categories (colored circles, letters) and stimulation sites (right, left PPC). The results showed a significant (Experiment 1) or trending (Experiment 2) WMC x stimulation interaction. Compared to tDCS, after HD-tDCS the retro-cueing benefit was significantly greater for the low WMC group but numerically worse for the high WMC group. These data highlight the importance of considering group differences when using non-invasive neurostimulation techniques. PMID- 27369326 TI - Pain relief induces dopamine release in the rat nucleus accumbens during the early but not late phase of neuropathic pain. AB - Comorbidity of chronic pain and depression has long been recognized in the clinic, and preclinical studies have reported depression-like behaviors in animal models of chronic pain. These findings suggest a common neuronal basis for chronic pain and depression. The neuronal pathway from the ventral tegmental area to the nucleus accumbens (NAc) is critical in the mesolimbic dopamine (DA) reward circuit, and dysfunction of this pathway has been implicated in depression. Although time-dependent development of depression-related behaviors has been reported in chronic pain animals, time-dependent functional changes in this pathway remain to be examined. To address this issue, we examined the effects of two types of rewards, pain relief by intrathecal injection of pregabalin (100MUg in 10MUL phosphate buffered saline) and 30% sucrose solution intake, on intra-NAc DA release in rats subjected to spinal nerve ligation (SNL). Specifically, the effects were investigated during the early (17-20days after ligation) and late (31-34days after ligation) phases of neuropathic pain. Pain relief increased the intra-NAc DA levels in the SNL rats during the early but not late phase of neuropathic pain. Intake of the sucrose solution increased the intra-NAc DA levels both in the SNL and sham animals during the early phase of neuropathic pain, while it induced DA release in the sham but not SNL animals during the late phase. These results suggest that dysfunction of the mesolimbic DA reward circuit develops in a time-dependent manner. Mesolimbic DA reward circuit dysfunction might be a common neuronal mechanism underlying chronic pain and depression, and a potential target for novel analgesic and antidepressant medications. PMID- 27369327 TI - Alterations of miRNAs reveal a dysregulated molecular regulatory network in Parkinson's disease striatum. AB - Molecular adaptations in the striatum mediated by dopamine (DA) denervation and/or levodopa (L-dopa) treatments have been implicated in the motor deficits found in Parkinson's disease (PD). Alterations in inflammatory response mechanisms and glutamatergic neurotransmission are reported to play important roles in mediating these changes. However, the mechanisms mediating the molecular adaptations in the striatum are not well understood. Small non-coding microRNAs (miRNAs) influence numerous biological processes including the development and maintenance of striatal neurons by regulating gene expression post transcriptionally. To investigate miRNA function in human PD striatum, we examined the global expression of miRNAs in postmortem putamen (putamen along with caudate forms the striatum) tissues obtained from PD patients and neurologically normal controls using Nanostring miRNA assays. We found that 6 miRNAs were significantly (p<=0.05) upregulated and 7 miRNAs were downregulated in PD putamen when compared with control. The differential expression (DE) of the 4 highest scoring miRNAs was further confirmed by reverse transcription polymerase chain reaction. Ingenuity pathway analysis demonstrated that these miRNAs are enriched in the processes of inflammatory responses. We found that the expression of DE miRNAs in PD putamen negatively correlates with the expression of gene transcripts implicated in inflammatory response with p53 and NF-kB as central signaling molecules. Taken together, our results suggest that in PD striatum, the DE miRNAs are associated with the oxidative stress pathway. This mechanism may contribute to the molecular adaptations and related motor complications found in PD. PMID- 27369329 TI - [Not Available]. PMID- 27369328 TI - [Not Available]. PMID- 27369330 TI - [Not Available]. PMID- 27369331 TI - [Not Available]. PMID- 27369332 TI - [Not Available]. PMID- 27369333 TI - [Not Available]. PMID- 27369335 TI - [Not Available]. PMID- 27369334 TI - [Not Available]. PMID- 27369336 TI - [Not Available]. PMID- 27369337 TI - [Not Available]. PMID- 27369339 TI - [Not Available]. PMID- 27369338 TI - [Not Available]. PMID- 27369340 TI - [Not Available]. PMID- 27369341 TI - [Not Available]. PMID- 27369343 TI - [Not Available]. PMID- 27369342 TI - [Not Available]. PMID- 27369344 TI - [Not Available]. PMID- 27369345 TI - [Not Available]. PMID- 27369346 TI - [Not Available]. PMID- 27369347 TI - [Not Available]. PMID- 27369348 TI - [Not Available]. PMID- 27369349 TI - [Not Available]. PMID- 27369350 TI - [Not Available]. PMID- 27369351 TI - [Not Available]. PMID- 27369352 TI - [Not Available]. PMID- 27369353 TI - [Not Available]. PMID- 27369354 TI - [Not Available]. PMID- 27369355 TI - A case of progressive breathlessness post partum. PMID- 27369356 TI - Infant weight trajectories and early childhood wheezing: the NINFEA birth cohort study. AB - BACKGROUND: Rapid postnatal weight gain has been associated with wheezing and asthma in children, but it remains unclear whether it acts independently of overweight. We aimed to disentangle the roles of infant's size and weight gain velocity in the development of wheezing in early childhood using a novel method that allows for mutual adjustment for different aspects of growth. METHODS: Data were obtained from the NINFEA questionnaires where weight measurements from birth up to 18 months of age were assessed in 4492 term singletons. Wheezing was defined as at least one episode of wheezing/whistling in the chest occurring between 6 and 18 months of age. The SuperImposition by Translation And Rotation model was used to estimate individual weight trajectories defined by three child specific parameters: size, velocity and tempo, that is age at peak weight velocity. These parameters were standardised and related to wheezing using logistic regression with effects expressed as an increase of one SD. RESULTS: A median of five weight measurements per child were obtained. Infant size (OR=1.28; 95% CI 1.12 to 1.46) and weight gain velocity (OR=1.30; 95% CI 1.15 to 1.48) were independently positively associated with wheezing. We found no evidence of an effect of tempo on infant wheezing. The estimates were changed only minimally after adjustment for potential confounders. CONCLUSIONS: Faster growth and larger size in the first 18 months of life are both independently associated with an increased risk of wheezing. These findings suggest that early growth patterns play a role in shaping the occurrence of wheezing. PMID- 27369357 TI - Local networks of community and healthcare organisations: a mixed methods study. AB - BACKGROUND: Local collaboration of community organisations and healthcare organisations is seen as relevant for the efficiency and efficacy of health and social care because of their potential role in providing social involvement which may reduce the need for the utilisation of formal services. Care organisations connect to each other in different ways, thus comprising an organisational network. This study aimed to describe and explore organisational networks with respect to their activities for people with diabetes mellitus type 2 and potential mechanisms of effective collaboration. Collaboration could include, for example, referring to each other and organising activities together. Potential mechanisms are navigation, negotiation and contagion. METHODS: A mixed methods study was conducted in an urban and a rural area in the Netherlands. The participating organisations were mentioned by a sample of diabetes patients in these regions and by organisations' representatives in a snowballing procedure. Next a quantitative survey and a semi-structured interview were conducted, including 35 representatives of these local organisations. The social network analysis methods was used to map and characterise the organisational networks based on results from the survey. A thematic analysis of interviews was undertaken to identify how three mechanisms (navigation, negotiation and contagion) were used in the collaboration. RESULTS: Both interviews and network structures showed evidence of navigation-related mechanisms. Organisations referred patients with diabetes to services within their organisation or to relevant services provided by other organisations. Hardly any negotiation or contagion-related mechanisms were identified. If negotiation between organisations was found, it seemed externally enforced. The density, centrality, and reciprocity in the networks seemed low to facilitate contagion of practices. Some organisations reported actions that could have impacted on contagion. Representatives emphasized the need of network collaboration with local or regional community and healthcare organisations. CONCLUSION: The study suggests that navigation to resources is a relevant theme in organisational networks, which could be targeted by interventions. More research is needed to explore the relevance of other network-related mechanisms. PMID- 27369358 TI - Autonomic nervous system involvement in the giant axonal neuropathy (GAN) KO mouse: implications for human disease. AB - PURPOSE: Giant axonal neuropathy (GAN) is an inherited severe sensorimotor neuropathy. The aim of this research was to investigate the neuropathologic features and clinical autonomic nervous system (ANS) phenotype in two GAN knockout (KO) mouse models. Little is known about ANS involvement in GAN in humans, but autonomic signs and symptoms are commonly reported in early childhood. METHODS: Routine histology and immunohistochemistry was performed on GAN KO mouse specimens taken at various ages. Enteric dysfunction was assessed by quantifying the frequency, weight, and water content of defecation in GAN KO mice. RESULTS: Histological examination of the enteric, parasympathetic and sympathetic ANS of GAN KO mice revealed pronounced and widespread neuronal perikaryal intermediate filament inclusions. These neuronal inclusions served as an easily identifiable, early marker of GAN in young GAN KO mice. Functional studies identified an age-dependent alteration in fecal weight and defecation frequency in GAN KO mice. CONCLUSIONS: For the first time in the GAN KO mouse model, we described the early, pronounced and widespread neuropathologic features involving the ANS. In addition, we provided evidence for a clinical autonomic phenotype in GAN KO mice, reflected in abnormal gastrointestinal function. These findings in GAN KO mice suggest that consideration should be given to ANS involvement in human GAN, especially when considering treatments and patient care. PMID- 27369359 TI - Effects of TP53 and PIK3CA mutations in early breast cancer: a matter of co mutation and tumor-infiltrating lymphocytes. AB - The purpose of this study is to investigate whether the outcome of breast cancer (BC) patients treated with adjuvant chemotherapy is affected by co-mutated TP53 and PIK3CA according to stromal tumor-infiltrating lymphocytes (TILs). Paraffin tumors of all clinical subtypes from 1661 patients with operable breast cancer who were treated within 4 adjuvant trials with anthracycline-taxanes chemotherapy were informative for TP53 and PIK3CA mutation status (semiconductor sequencing genotyping) and for stromal TILs density. Disease-free survival (DFS) was examined. TP53 mutations were associated with higher (p < 0.001) and PIK3CA with lower (p = 0.004) TILs in an ER /PgR-specific manner (p < 0.001). Mutations did not affect the favorable DFS of patients with lymphocyte-predominant (LP) BC. Within non-LPBC, PIK3CA-only mutations conferred best, while TP53-PIK3CA co mutations (6 % of all tumors) conferred worst DFS (HR 0.59; 95 % CI 0.44-0.79; p = 0.001 for PIK3CA-only). TP53-only mutations were unfavorable in patients with lower TILs, while patients with lower TILs performed worse if their tumors carried TP53-only mutations (interaction p = 0.046). Multivariate analysis revealed favorable PIK3CA-only mutations in non-LPBC (HR 0.64; 95 % CI 0.47-0.88; p = 0.007), and unfavorable TP53 mutations in ER/PgRpos/HER2neg (HR 1.55; 95 % CI 1.07-2.24; p = 0.021). Mutations did not interact with TILs in non-LP triple negative and HER2-positive patients. TP53 and PIK3CA mutations appear to have diverse effects on the outcome of early BC patients, according to whether these genes are co-mutated or not, and for TP53 according to TILs density and ER/PgR status. These findings need to be considered when evaluating the effect of these two most frequently mutated genes in the context of large clinical trials. PMID- 27369360 TI - Retraction: Sirtuin-3 deacetylation of cyclophilin D induces dissociation of hexokinase II from the mitochondria. PMID- 27369361 TI - Retraction: Ethanol sensitizes mitochondria to the permeability transition by inhibiting deacetylation of cyclophilin-D mediated by sirtuin-3. PMID- 27369362 TI - Retraction: GRIM-19-mediated translocation of STAT3 to mitochondria is necessary for TNF-induced necroptosis. PMID- 27369363 TI - Retraction: Sirtuin-3 modulates Bak- and Bax-dependent apoptosis. PMID- 27369364 TI - Retraction: Mitoneet mediates TNFalpha-induced necroptosis promoted by exposure to fructose and ethanol. PMID- 27369365 TI - Depigmentation during vitiligo activity spares epithelial grafted areas. AB - BACKGROUND: Vitiligo is a depigmenting disease characterized by episodes of stability and activity without a fixed sequence, and active phases demonstrate immune attacks toward vulnerable melanocytes. Epithelial grafts were introduced to treat recalcitrant vitiligo patches aiming to provide new generations of melanocytes. AIMS: The aim of study was to evaluate the possible permanency of succeeded epithelial grafts during a coming activity episode. METHODS: This study included 20 nonsegmental vitiligo cases. They were epithelial grafted, success was maintained with the use of UV sessions for a year, and further follow-up was allowed until new phases of activity developed. RESULTS: The grafted areas, in all cases, were spared during the activity episodes in spite of the development of new depigmented lesions in other parts of skin neighboring the grafted areas or in remote sites. CONCLUSION: The permanency of epithelial grafts in spite of disease reactivity is a good sign and magnifies the value of surgical approaches in management of vitiligo. New genetically different melanocytes should have been provided and were able to resist the new immune attacks in spite of the yielding of other skin melanocytes. PMID- 27369366 TI - [Not Available]. PMID- 27369367 TI - [Not Available]. PMID- 27369368 TI - [Not Available]. PMID- 27369369 TI - [Not Available]. PMID- 27369370 TI - [Not Available]. PMID- 27369371 TI - [Not Available]. PMID- 27369372 TI - [Not Available]. PMID- 27369373 TI - A simplified approach to estimating the distribution of occasionally-consumed dietary components, applied to alcohol intake. AB - BACKGROUND: Within-person variation in dietary records can lead to biased estimates of the distribution of food intake. Quantile estimation is especially relevant in the case of skewed distributions and in the estimation of under- or over-consumption. The analysis of the intake distributions of occasionally consumed foods presents further challenges due to the high frequency of zero records. Two-part mixed-effects models account for excess-zeros, daily variation and correlation arising from repeated individual dietary records. In practice, the application of the two-part model with random effects involves Monte Carlo (MC) simulations. However, these can be time-consuming and the precision of MC estimates depends on the size of the simulated data which can hinder reproducibility of results. METHODS: We propose a new approach based on numerical integration as an alternative to MC simulations to estimate the distribution of occasionally-consumed foods in sub-populations. The proposed approach and MC methods are compared by analysing the alcohol intake distribution in a sub population of individuals at risk of developing metabolic syndrome. RESULTS: The rate of convergence of the results of MC simulations to the results of our proposed method is model-specific, depends on the number of draws from the target distribution, and is relatively slower at the tails of the distribution. Our data analyses also show that model misspecification can lead to incorrect model parameter estimates. For example, under the wrong model assumption of zero correlation between the components, one of the predictors turned out as non significant at 5 % significance level (p-value 0.062) but it was estimated as significant in the correctly specified model (p-value 0.016). CONCLUSIONS: The proposed approach for the analysis of the intake distributions of occasionally consumed foods provides a quicker and more precise alternative to MC simulation methods, particularly in the estimation of under- or over-consumption. The method is readily available to non-technical users in contrast to MC methods whereby the simulation error may be substantial and difficult to evaluate. PMID- 27369374 TI - "It's for us -newcomers, LGBTQ persons, and HIV-positive persons. You feel free to be": a qualitative study exploring social support group participation among African and Caribbean lesbian, gay, bisexual and transgender newcomers and refugees in Toronto, Canada. AB - BACKGROUND: Stigma and discrimination harm the wellbeing of lesbian, gay, bisexual and transgender (LGBT) people and contribute to migration from contexts of sexual persecution and criminalization. Yet LGBT newcomers and refugees often face marginalization and struggles meeting the social determinants of health (SDOH) following immigration to countries such as Canada. Social isolation is a key social determinant of health that may play a significant role in shaping health disparities among LGBT newcomers and refugees. Social support may moderate the effect of stressors on mental health, reduce social isolation, and build social networks. Scant research, however, has examined social support groups targeting LGBT newcomers and refugees. The purpose of this qualitative study was to explore experiences of social support group participation among LGBT African and Caribbean newcomers and refugees in an urban Canadian city. METHODS: We conducted 3 focus groups with a venue-based sample of LGBT African and Caribbean newcomers and refugees (n = 29) who attended social support groups at an ethno specific AIDS Service Organization. Focus groups followed a semi-structured interview guide and were analyzed using narrative thematic techniques. RESULTS: Participant narratives highlighted immigration stressors, social isolation, mental health issues, and challenges meeting the SDOH. Findings reveal multi level benefits of social support group participation at intrapersonal (self acceptance, improved mental health), interpersonal (reduced isolation, friendships), community (reciprocity, reduced stigma and discrimination), and structural (housing, employment, immigration, health care) levels. CONCLUSIONS: Findings suggest that social support groups tailored for LGBT African and Caribbean newcomers and refugees can address social isolation, community resilience, and enhance resource access. Health care providers can provide support groups, culturally and LGBT competent health services, and resource access to promote LGBT newcomers and refugees' health and wellbeing. PMID- 27369376 TI - High-resolution mass spectrometry in toxicology: current status and future perspectives. AB - This paper reviews high-resolution mass spectrometry (HRMS) approaches using time of-flight or Orbitrap techniques for research and application in various toxicology fields, particularly in clinical toxicology and forensic toxicology published since 2013 and referenced in PubMed. In the introduction, an overview on applications of HRMS in various toxicology fields is given with reference to current review articles. Papers concerning HRMS in metabolism, screening, and quantification of pharmaceuticals, drugs of abuse, and toxins in human body samples are critically reviewed. Finally, a discussion on advantages as well as limitations and future perspectives of these methods is included. PMID- 27369375 TI - Activation of the Nrf2 signaling pathway in usnic acid-induced toxicity in HepG2 cells. AB - Many usnic acid-containing dietary supplements have been marketed as weight loss agents, although severe hepatotoxicity and acute liver failure have been associated with their overuse. Our previous mechanistic studies revealed that autophagy, disturbance of calcium homeostasis, and ER stress are involved in usnic acid-induced toxicity. In this study, we investigated the role of oxidative stress and the Nrf2 signaling pathway in usnic acid-induced toxicity in HepG2 cells. We found that a 24-h treatment with usnic acid caused DNA damage and S phase cell cycle arrest in a concentration-dependent manner. Usnic acid also triggered oxidative stress as demonstrated by increased reactive oxygen species generation and glutathione depletion. Short-term treatment (6 h) with usnic acid significantly increased the protein level for Nrf2 (nuclear factor erythroid 2 related factor 2), promoted Nrf2 translocation to the nucleus, up-regulated antioxidant response element (ARE)-luciferase reporter activity, and induced the expression of Nrf2-regulated targets, including glutathione reductase, glutathione S-transferase, and NAD(P)H quinone oxidoreductase-1 (NQO1). Furthermore, knockdown of Nrf2 with shRNA potentiated usnic acid-induced DNA damage and cytotoxicity. Taken together, our results show that usnic acid causes cell cycle dysregulation, DNA damage, and oxidative stress and that the Nrf2 signaling pathway is activated in usnic acid-induced cytotoxicity. PMID- 27369377 TI - A basic domain in the histone H2B N-terminal tail is important for nucleosome assembly by FACT. AB - Nucleosome assembly in vivo requires assembly factors, such as histone chaperones, to bind to histones and mediate their deposition onto DNA. In yeast, the essential histone chaperone FACT (FAcilitates Chromatin Transcription) functions in nucleosome assembly and H2A-H2B deposition during transcription elongation and DNA replication. Recent studies have identified candidate histone residues that mediate FACT binding to histones, but it is not known which histone residues are important for FACT to deposit histones onto DNA during nucleosome assembly. In this study, we report that the histone H2B repression (HBR) domain within the H2B N-terminal tail is important for histone deposition by FACT. Deletion of the HBR domain causes significant defects in histone occupancy in the yeast genome, particularly at HBR-repressed genes, and a pronounced increase in H2A-H2B dimers that remain bound to FACT in vivo Moreover, the HBR domain is required for purified FACT to efficiently assemble recombinant nucleosomes in vitro We propose that the interaction between the highly basic HBR domain and DNA plays an important role in stabilizing the nascent nucleosome during the process of histone H2A-H2B deposition by FACT. PMID- 27369378 TI - Structure and mechanism of a molecular rheostat, an RNA thermometer that modulates immune evasion by Neisseria meningitidis. AB - Neisseria meningitidis causes bacterial meningitis and septicemia. It evades the host complement system by upregulating expression of immune evasion factors in response to changes in temperature. RNA thermometers within mRNAs control expression of bacterial immune evasion factors, including CssA, in the 5' untranslated region of the operon for capsule biosynthesis. We dissect the molecular mechanisms of thermoregulation and report the structure of the CssA thermometer. We show that the RNA thermometer acts as a rheostat, whose stability is optimized to respond in a small temperature range around 37 degrees C as occur within the upper airways during infection. Small increases in temperature gradually open up the structure to allow progressively increased access to the ribosome binding site. Even small changes in stability induced by mutations of imperfect base pairs, as in naturally occurring polymorphisms, shift the thermometer response outside of the desired temperature range, suggesting that its activity could be modulated by pharmacological intervention. PMID- 27369379 TI - Combination probes with intercalating anchors and proximal fluorophores for DNA and RNA detection. AB - A new class of modified oligonucleotides (combination probes) has been designed and synthesised for use in genetic analysis and RNA detection. Their chemical structure combines an intercalating anchor with a reporter fluorophore on the same thymine nucleobase. The intercalator (thiazole orange or benzothiazole orange) provides an anchor, which upon hybridisation of the probe to its target becomes fluorescent and simultaneously stabilizes the duplex. The anchor is able to communicate via FRET to a proximal reporter dye (e.g. ROX, HEX, ATTO647N, FAM) whose fluorescence signal can be monitored on a range of analytical devices. Direct excitation of the reporter dye provides an alternative signalling mechanism. In both signalling modes, fluorescence in the unhybridised probe is switched off by collisional quenching between adjacent intercalator and reporter dyes. Single nucleotide polymorphisms in DNA and RNA targets are identified by differences in the duplex melting temperature, and the use of short hybridization probes, made possible by the stabilisation provided by the intercalator, enhances mismatch discrimination. Unlike other fluorogenic probe systems, placing the fluorophore and quencher on the same nucleobase facilitates the design of short probes containing multiple modifications. The ability to detect both DNA and RNA sequences suggests applications in cellular imaging and diagnostics. PMID- 27369381 TI - Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site. AB - Integrase strand transfer inhibitors (INSTIs) are highly effective against HIV infections. Co-crystal structures of the prototype foamy virus intasome have shown that all three FDA-approved drugs, raltegravir (RAL), elvitegravir and dolutegravir (DTG), act as interfacial inhibitors during the strand transfer (ST) integration step. However, these structures give only a partial sense for the limited inhibition of the 3'-processing reaction by INSTIs and how INSTIs can be modified to overcome drug resistance, notably against the G140S-Q148H double mutation. Based on biochemical experiments with modified oligonucleotides, we demonstrate that both the viral DNA +1 and -1 bases, which flank the 3' processing site, play a critical role for 3'-processing efficiency and inhibition by RAL and DTG. In addition, the G140S-Q148H (SH) mutant integrase, which has a reduced 3'-processing activity, becomes more active and more resistant to inhibition of 3'-processing by RAL and DTG in the absence of the -1 and +1 bases. Molecular modeling of HIV-1 integrase, together with biochemical data, indicate that the conserved residue Q146 in the flexible loop of HIV-1 integrase is critical for productive viral DNA binding through specific contacts with the virus DNA ends in the 3'-processing and ST reactions. The potency of integrase inhibitors against 3'-processing and their ability to overcome resistance is discussed. PMID- 27369380 TI - Cracking the control of RNA polymerase II elongation by 7SK snRNP and P-TEFb. AB - Release of RNA polymerase II (Pol II) from promoter-proximal pausing has emerged as a critical step regulating gene expression in multicellular organisms. The transition of Pol II into productive elongation requires the kinase activity of positive transcription elongation factor b (P-TEFb), which is itself under a stringent control by the inhibitory 7SK small nuclear ribonucleoprotein (7SK snRNP) complex. Here, we provide an overview on stimulating Pol II pause release by P-TEFb and on sequestering P-TEFb into 7SK snRNP. Furthermore, we highlight mechanisms that govern anchoring of 7SK snRNP to chromatin as well as means that release P-TEFb from the inhibitory complex, and propose a unifying model of P TEFb activation on chromatin. Collectively, these studies shine a spotlight on the central role of RNA binding proteins (RBPs) in directing the inhibition and activation of P-TEFb, providing a compelling paradigm for controlling Pol II transcription with a non-coding RNA. PMID- 27369382 TI - Sir2 regulates stability of repetitive domains differentially in the human fungal pathogen Candida albicans. AB - DNA repeats, found at the ribosomal DNA locus, telomeres and subtelomeric regions, are unstable sites of eukaryotic genomes. A fine balance between genetic variability and genomic stability tunes plasticity of these chromosomal regions. This tuning mechanism is particularly important for organisms such as microbial pathogens that utilise genome plasticity as a strategy for adaptation. For the first time, we analyse mechanisms promoting genome stability at the rDNA locus and subtelomeric regions in the most common human fungal pathogen: Candida albicans In this organism, the histone deacetylase Sir2, the master regulator of heterochromatin, has acquired novel functions in regulating genome stability. Contrary to any other systems analysed, C. albicans Sir2 is largely dispensable for repressing recombination at the rDNA locus. We demonstrate that recombination at subtelomeric regions is controlled by a novel DNA element, the TLO Recombination Element, TRE, and by Sir2. While the TRE element promotes high levels of recombination, Sir2 represses this recombination rate. Finally, we demonstrate that, in C. albicans, mechanisms regulating genome stability are plastic as different environmental stress conditions lead to general genome instability and mask the Sir2-mediated recombination control at subtelomeres. Our data highlight how mechanisms regulating genome stability are rewired in C. albicans. PMID- 27369383 TI - Global intron retention mediated gene regulation during CD4+ T cell activation. AB - T cell activation is a well-established model for studying cellular responses to exogenous stimulation. Using strand-specific RNA-seq, we observed that intron retention is prevalent in polyadenylated transcripts in resting CD4(+) T cells and is significantly reduced upon T cell activation. Several lines of evidence suggest that intron-retained transcripts are less stable than fully spliced transcripts. Strikingly, the decrease in intron retention (IR) levels correlate with the increase in steady-state mRNA levels. Further, the majority of the genes upregulated in activated T cells are accompanied by a significant reduction in IR. Of these 1583 genes, 185 genes are predominantly regulated at the IR level, and highly enriched in the proteasome pathway, which is essential for proper T cell proliferation and cytokine release. These observations were corroborated in both human and mouse CD4(+) T cells. Our study revealed a novel post transcriptional regulatory mechanism that may potentially contribute to coordinated and/or quick cellular responses to extracellular stimuli such as an acute infection. PMID- 27369385 TI - Enhanced insecticidal activity of Chilo iridescent virus expressing an insect specific neurotoxin. AB - Previously we have generated a recombinant Chilo iridescent virus (CIV) by inserting the green fluorescent protein gene (gfp) into the CIV 157L open reading frame (ORF) locus and showed that this recombinant (rCIV-Delta157L-gfp) was fully infectious both in cell culture as well as in insect larvae. This study opened up a new avenue for increasing the speed of kill of CIV and other iridoviruses by inserting virulence or toxin genes into the viral genome. In the current study we constructed a recombinant CIV (rCIV-Delta157L/gfp-AaIT) where the 157L ORF was replaced with both the AaIT neurotoxin gene from the scorpion Androctonus australis and the gfp gene, each under control of the viral major capsid protein (mcp) gene promoter. Recombinant virus was purified by successive rounds of plaque purification using Spodoptera frugiperda (Sf-9) cells. One-step growth curves for the recombinant viruses, rCIV-Delta157L/gfp-AaIT and rCIV-Delta157L gfp, and wild-type CIVs in Sf-9 cells showed similar profiles. AaIT toxin expression in infected third instar Galleria mellonella larvae was confirmed by western blot analysis using an antibody against the AaIT protein. rCIV Delta157L/gfp-AaIT infection at a concentration that kills 100% of the larvae caused paralysis in infected third instar G. mellonella larvae from two days after injection, whereas infection with non-AaIT containing viruses showed mortality starting much later (>10days). Bioassays on these larvae demonstrated that the speed of kill of CIV carrying AaIT was strikingly enhanced as compared to wild-type CIV. These results suggest that insertion of a toxin gene into CIV provides further opportunities to control a wide range of pest insects, such as weevils, using an iridovirus. PMID- 27369384 TI - The zinc fingers of YY1 bind single-stranded RNA with low sequence specificity. AB - Classical zinc fingers (ZFs) are traditionally considered to act as sequence specific DNA-binding domains. More recently, classical ZFs have been recognised as potential RNA-binding modules, raising the intriguing possibility that classical-ZF transcription factors are involved in post-transcriptional gene regulation via direct RNA binding. To date, however, only one classical ZF-RNA complex, that involving TFIIIA, has been structurally characterised. Yin Yang-1 (YY1) is a multi-functional transcription factor involved in many regulatory processes, and binds DNA via four classical ZFs. Recent evidence suggests that YY1 also interacts with RNA, but the molecular nature of the interaction remains unknown. In the present work, we directly assess the ability of YY1 to bind RNA using in vitro assays. Systematic Evolution of Ligands by EXponential enrichment (SELEX) was used to identify preferred RNA sequences bound by the YY1 ZFs from a randomised library over multiple rounds of selection. However, a strong motif was not consistently recovered, suggesting that the RNA sequence selectivity of these domains is modest. YY1 ZF residues involved in binding to single-stranded RNA were identified by NMR spectroscopy and found to be largely distinct from the set of residues involved in DNA binding, suggesting that interactions between YY1 and ssRNA constitute a separate mode of nucleic acid binding. Our data are consistent with recent reports that YY1 can bind to RNA in a low-specificity, yet physiologically relevant manner. PMID- 27369402 TI - [Not Available]. PMID- 27369403 TI - [Not Available]. PMID- 27369386 TI - First detection of Apis mellifera filamentous virus in Apis cerana cerana in China. AB - Although many honey bee RNA viruses have been correlated with colony declines, little is known regarding the potential role of DNA viruses. Here, we examined seemingly healthy and crawling bee samples from China using PCR to identify whether Apis mellifera filamentous virus (AmFV) was present in A. cerana cerana. The highest AmFV infection percentage among Chinese provinces occurred in crawling bees from Gansu province (85.48%), and the lowest was in bees from Beijing (31.58%). A phylogenetic analysis showed that the Chinese isolate of AmFV exhibited a high genetic similarity with isolates from Belgium, Switzerland and USA. This is the first report of AmFV infections in Chinese A. cerana cerana populations. PMID- 27369404 TI - [Not Available]. PMID- 27369405 TI - [Not Available]. PMID- 27369406 TI - [Not Available]. PMID- 27369407 TI - [Not Available]. PMID- 27369408 TI - [Not Available]. PMID- 27369409 TI - [Not Available]. PMID- 27369410 TI - [Not Available]. PMID- 27369411 TI - [Not Available]. PMID- 27369412 TI - [Not Available]. PMID- 27369413 TI - [Not Available]. PMID- 27369414 TI - [Not Available]. PMID- 27369416 TI - [Not Available]. PMID- 27369415 TI - [Not Available]. PMID- 27369417 TI - [Not Available]. PMID- 27369418 TI - [Not Available]. PMID- 27369420 TI - [Not Available]. PMID- 27369419 TI - [Not Available]. PMID- 27369421 TI - [Not Available]. PMID- 27369422 TI - [Not Available]. PMID- 27369423 TI - [Not Available]. PMID- 27369424 TI - [Not Available]. PMID- 27369425 TI - [Not Available]. PMID- 27369426 TI - [Not Available]. PMID- 27369428 TI - Genetic characterization of highly pathogenic avian influenza H5N1 viruses isolated from naturally infected pigeons in Egypt. AB - Avian influenza viruses impose serious public health burdens with significant mortality and morbidity not only in poultry but also in humans. While poultry susceptibility to avian influenza virus infection is well characterized, pigeons have been thought to have low susceptibility to these viruses. However, recent studies reported natural pigeon infections with highly pathogenic avian influenza H5N1 viruses. In Egypt, which is one of the H5N1 endemic areas for birds, pigeons are raised in towers built on farms in backyards and on house roofs, providing a potential risk for virus transmission from pigeons to humans. In this study, we performed genetic analysis of two H5N1 virus strains that were isolated from naturally infected pigeons in Egypt. Genetic and phylogenetic analyses showed that these viruses originated from Egyptian H5N1 viruses that were circulating in chickens or ducks. Several unique mutations, not reported before in any Egyptian isolates, were detected in the internal genes (i.e., polymerase residues PB1-V3D, PB1-K363R, PA-A369V, and PA-V602I; nucleoprotein residue NP-R38K; and nonstructural protein residues NS1-D120N and NS2-F55C). Our findings suggested that pigeons are naturally infected with H5N1 virus and can be a potential reservoir for transmission to humans, and showed the importance of genetic analysis of H5N1 internal genes. PMID- 27369429 TI - Detection of novel ferret coronaviruses and evidence of recombination among ferret coronaviruses. AB - In an epidemiological study of ferret coronaviruses (FRCoVs), novel FRCoV strains (Saitama-1 and Aichi-1) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequence analysis of partial RNA-dependent RNA polymerase (RdRp) genes. Phylogenetic analysis indicated that these strains belonged to different clusters from other FRCoV strains. Next, the nucleotide sequence of the 3'-terminal region of Saitama-1 (8271 bases) strain was determined and compared with those of the other FRCoVs, indicating that the Saitama-1 strain differed from the previously reported MSU-1 and MSU-2 strains in the regions encoding spike (S) protein, nucleocapsid, and open reading frame 7b. Furthermore, the results of SimPlot analysis indicated that FRCoV (MSU-2 strain) emerged via a recombination event of S protein between the MSU-1 and Saitama-1 strains. This mechanism is similar to that responsible for the emergence of type II feline coronavirus. This information will be useful for understanding the pathogenesis of FRCoV in ferrets. PMID- 27369430 TI - Taste of Clindamycin and Acetaminophen. AB - This study evaluated the taste palatability of liquid clindamycin and acetaminophen products on the market. Subjects rated the palatability of 3 clindamycin suspensions, 1 amoxicillin suspension (tasted twice), an acetaminophen elixir, and an acetaminophen suspension in a randomized blinded fashion on a 0 to 5 scale. Forty-six adults aged 20 to 82 years volunteered for this study. Means (and 95% confidence intervals) were as follows: amoxicillin first taste 3.6 (3.3-3.9), amoxicillin-second taste 3.5 (3.2-3.7). Clindamycin Rising, Perrigo, Greenstone; 2.0 (1.6-2.5), 3.0 (2.7-3.3), and 2.2 (1.8-2.6), respectively. Acetaminophen elixir 0.6 (0.4-0.8) and acetaminophen suspension 3.4 (3.1-3.6). One clindamycin tasted significantly better than the others. Additionally, although 2 acetaminophen formulations are currently available over the-counter, the suspension is more palatable and less costly. Medicaid drug programs that perpetuate the use of elixir should change their coverage to save money and provide patients access to better tasting acetaminophen. PMID- 27369432 TI - [Not Available]. PMID- 27369433 TI - [Not Available]. PMID- 27369431 TI - Expression of CCL21 in Ewing sarcoma shows an inverse correlation with metastases and is a candidate target for immunotherapy. AB - Ewing sarcoma is an aggressive neoplasm predominantly occurring in adolescents and has a poor prognosis when metastasized. For patients with metastatic disease in particular, immunotherapy has been proposed as possible beneficial additive therapy. CCL21 activation-based immunotherapy was successful in preclinical studies in other tumor types; therefore, we investigated CCL21 expression in Ewing sarcoma as potential target for immunotherapy. The CCL21 RNA expression was determined in 21 Ewing sarcoma cell lines and 18 primary therapy-naive Ewing sarcoma samples. In the tumor samples, this was correlated with the number and CD4(+)/CD8(+) ratio of infiltrating T cells and clinical parameters. Higher RNA expression levels of CCL21 significantly correlated with a lower CD4(+)/CD8(+) T cell ratio (P = 0.009), good chemotherapeutic response (P = 0.01) and improved outcome (P < 0.001). In patients with metastases, CCL21 expression was significantly lower than in patients without (P < 0.0005). CCL21 expression was significantly higher in Ewing sarcoma tissue samples compared to cell lines (P < 0.01), implying the involvement of a stromal factor. Protein expression analysis of CCL21 and its receptor CCR7 in 24 therapy-naive tumors showed that there was no expression in all bar one Ewing sarcoma cells. In conclusion, CCL21 is expressed in clinical Ewing sarcoma samples by nontumor-infiltrating immune cells. The observed positive correlation with survival implies that CCL21 might be a potential prognostic marker for Ewing sarcoma and marks the potential of CCL21 immunotherapy for use in Ewing sarcoma. PMID- 27369434 TI - [Not Available]. PMID- 27369435 TI - [Not Available]. PMID- 27369436 TI - [Not Available]. PMID- 27369437 TI - [Not Available]. PMID- 27369438 TI - [Not Available]. PMID- 27369439 TI - [Not Available]. PMID- 27369440 TI - [Not Available]. PMID- 27369441 TI - [Not Available]. PMID- 27369442 TI - [Not Available]. PMID- 27369443 TI - [Not Available]. PMID- 27369444 TI - [Not Available]. PMID- 27369445 TI - [Not Available]. PMID- 27369446 TI - [Not Available]. PMID- 27369447 TI - Liver and cholestatic parameters as prognostic biomarkers of in-hospital MACE in patients with STEMI. AB - BACKGROUND: Liver and cholestatic parameters are increased in ST-segment elevation myocardial infarction (STEMI). The aim of the present study was to evaluate the prognostic value of these parameters to predict in-hospital major adverse cardiac events (MACE) in patients after STEMI. MATERIALS AND METHODS: Blood samples of patients with STEMI, who underwent percutaneous coronary intervention (PCI) and stent implantation, were retrospectively analysed and correlated with in-hospital events. RESULTS: The study population consisted of 847 consecutive patients (62.4 +/- 13.43 years; 73.8% male). The total in hospital MACE rate was 9.8%, driven by death of any cause (8.4%). The Mann Whitney U-test revealed that liver and cholestatic parameters (alanine transaminase P < 0.0001, aspartate transaminase P < 0.0001, alkaline phosphatase (AP) P < 0.0001, gamma-glutamyl transferase P = 0.0006 and total bilirubin P = 0.0023) were significantly higher in the MACE group. Further logistic regression analyses confirmed the correlation between MACE and all five laboratory markers, even after adjustment for age and heart enzymes. Logistic regression model revealed AP to be the best predictor for worth outcome (OR 1.0188; 95% CI 1.0118 1.0258; P < 0.0001). CONCLUSION: Liver and cholestatic parameters are elevated in patients after STEMI. Increased AP is associated with in-hospital event rates. PMID- 27369448 TI - Human neural progenitor cells decrease photoreceptor degeneration, normalize opsin distribution and support synapse structure in cultured porcine retina. AB - Retinal neurodegenerative disorders like retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy and retinal detachment decrease retinal functionality leading to visual impairment. The pathological events are characterized by photoreceptor degeneration, synaptic disassembly, remodeling of postsynaptic neurons and activation of glial cells. Despite intense research, no effective treatment has been found for these disorders. The current study explores the potential of human neural progenitor cell (hNPC) derived factors to slow the degenerative processes in adult porcine retinal explants. Retinas were cultured for 3 days with or without hNPCs as a feeder layer and investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), immunohistochemical, western blot and quantitative real time-polymerase chain reaction (qRT-PCR) techniques. TUNEL showed that hNPCs had the capacity to limit photoreceptor cell death. Among cone photoreceptors, hNPC coculture resulted in better maintenance of cone outer segments and reduced opsin mislocalization. Additionally, maintained synaptic structural integrity and preservation of second order calbindin positive horizontal cells was also observed. However, Muller cell gliosis only seemed to be alleviated in terms of reduced Muller cell density. Our observations indicate that at 3 days of coculture, hNPC derived factors had the capacity to protect photoreceptors, maintain synaptic integrity and support horizontal cell survival. Human neural progenitor cell applied treatment modalities may be an effective strategy to help maintain retinal functionality in neurodegenerative pathologies. Whether hNPCs can independently hinder Muller cell gliosis by utilizing higher concentrations or by combination with other pharmacological agents still needs to be determined. PMID- 27369449 TI - Pulsed ultrasound expands the extracellular and perivascular spaces of the brain. AB - Diffusion within the extracellular and perivascular spaces of the brain plays an important role in biological processes, therapeutic delivery, and clearance mechanisms within the central nervous system. Recently, ultrasound has been used to enhance the dispersion of locally administered molecules and particles within the brain, but ultrasound-mediated effects on the brain parenchyma remain poorly understood. We combined an electron microscopy-based ultrastructural analysis with high-resolution tracking of non-adhesive nanoparticles in order to probe changes in the extracellular and perivascular spaces of the brain following a non destructive pulsed ultrasound regimen known to alter diffusivity in other tissues. Freshly obtained rat brain neocortical slices underwent sham treatment or pulsed, low intensity ultrasound for 5min at 1MHz. Transmission electron microscopy revealed intact cells and blood vessels and evidence of enlarged spaces, particularly adjacent to blood vessels, in ultrasound-treated brain slices. Additionally, ultrasound significantly increased the diffusion rate of 100nm, 200nm, and 500nm nanoparticles that were injected into the brain slices, while 2000nm particles were unaffected. In ultrasound-treated slices, 91.6% of the 100nm particles, 20.7% of the 200nm particles, 13.8% of the 500nm particles, and 0% of the 2000nm particles exhibited diffusive motion. Thus, pulsed ultrasound can have meaningful structural effects on the brain extracellular and perivascular spaces without evidence of tissue disruption. PMID- 27369450 TI - Probing amyloid beta-induced cell death using a fluorescence-peptide conjugate in Alzheimer's disease mouse model. AB - With the increasing worldwide incidence of Alzheimer's disease (AD), there is a critical need for the discovery of more effective diagnostic methods. However, development of diagnostic tools in AD has been hindered by obstacles such as the absence of exact biomarkers. Apoptosis caused by amyloid-beta (Abeta) plays an important role in AD pathology; therefore, provides an attractive biological target for the diagnosis of AD. The present study aimed to evaluate the potential of small peptide, named ApoPep-1 (Apoptosis-targeting peptide-1) as a new apoptosis imaging agent in AD. The fluorescein-conjugated ApoPep-1, but not the control peptide, targeted apoptotic cells in the brain of amyloid precursor protein (APP)/presenilin 1 (PS1) mice. We also observed fluorescence signals during in vivo imaging of apoptotic cells using ApoPep-1, and fluorescence levels increased in an age-dependent manner in APP/PS1 mice. Ex vivo imaging of isolated brains in APP/PS1 mice further confirmed the targeting of ApoPep-1 to apoptotic cells. The fluorescein-labeled ApoPep-1 co-localized with brain cells such as neurons, astrocytes, and microglia, all of which undergo apoptosis in the APP/PS1 mice brain. These findings demonstrate that ApoPep-1 can target apoptotic brain cells, and be used for experimental investigations relevant to apoptosis in AD. PMID- 27369452 TI - SAPHO: Treatment options including bisphosphonates. AB - INTRODUCTION: Both the diagnosis and treatment of the syndrome of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) remain difficult. We describe a case series of 21 patients with SAPHO and their response to several pharmacological treatments. METHODS: Clinical and biochemical data, along with medical imaging, were collected from the medical records of 21 patients, diagnosed as SAPHO during follow-up between 2005 and 2013. Symptoms and inflammatory markers were recorded twice, once at first patient presentation, and once at the end of follow-up. Synovitis, acne, pustulosis, hyperostosis, and osteitis were labeled as defining features. All treatment options were categorized according to their respective responses (full remission, partial remission, and no disease control). RESULTS: There was a female predominance and a median age of 32 years (range: 12-54 years). Median follow-up duration was 45 months (range: 0-188 months). Total prevalence of defining features in this cohort increased for each defining feature during follow-up, except for acne. All patients reached full or partial remission at the end of follow-up. A total of 14 patients were treated with bisphosphonates. Of which 8 of them went into full or partial remission. DISCUSSION AND CONCLUSION: In our case series, none of the patients had the full presentation of SAPHO at the first consultation. Some presented with symptoms suggestive for psoriatic arthritis. This explains why diagnosis of SAPHO can be challenging. Full remission was induced in the majority of individuals. Bisphosphonates seem to be a noteworthy treatment option. We suggest a prospective placebo-controlled clinical trial with bisphosphonates to confirm this observation. PMID- 27369451 TI - Discovery of a novel small molecule agonist scaffold for the APJ receptor. AB - The apelinergic system includes a series of endogenous peptides apelin, ELABELA/TODDLER and their 7-transmembrane G-protein coupled apelin receptor (APJ, AGTRL-1, APLNR). The APJ receptor is an attractive therapeutic target because of its involvement in cardiovascular diseases and potentially other disorders including liver fibrosis, obesity, diabetes, and neuroprotection. To date, pharmacological characterization of the APJ receptor has been limited due to the lack of small molecule functional agonists or antagonists. Through focused screening we identified a drug-like small molecule agonist hit 1 with a functional EC50 value of 21.5+/-5MUM and binding affinity (Ki) of 5.2+/-0.5MUM. Initial structure-activity studies afforded compound 22 having a 27-fold enhancement in potency and the first sub-micromolar full agonist with an EC50 value of 800+/-0.1nM and Ki of 1.3+/-0.3MUM. Preliminary SAR, synthetic methodology, and in vitro pharmacological characterization indicate this scaffold will serve as a favorable starting point for further refinement of APJ potency and selectivity. PMID- 27369453 TI - Recurrent hybridization and recent origin obscure phylogenetic relationships within the 'white-headed' gull (Larus sp.) complex. AB - Species complexes that have undergone recent radiations are often characterized by extensive allele sharing due to recent ancestry and (or) introgressive hybridization. This can result in discordant evolutionary histories of genes and heterogeneous genomes, making delineating species limits difficult. Here we examine the phylogenetic relationships among a complex group of birds, the white headed gulls (Aves: Laridae), which offer a unique window into the speciation process due to their recent evolutionary history and propensity to hybridize. Relationships were examined among 17 species (61 populations) using a multilocus approach, including mitochondrial and nuclear intron DNA sequences and microsatellite genotype information. Analyses of microsatellite and intron data resulted in some species-based groupings, although most species were not represented by a single cluster. Considerable allele and haplotype sharing among white-headed gull species was observed; no locus contained a species-specific clade. Despite this, our multilocus approach provided better resolution among some species than previous studies. Interestingly, most clades appear to correspond to geographic locality: our BEAST analysis recovered strong support for a northern European/Icelandic clade, a southern European/Russian clade, and a western North American/canus clade, with weak evidence for a high latitude clade spanning North America and northwestern Europe. This geographical structuring is concordant with behavioral observations of pervasive hybridization in areas of secondary contact. The extent of allele and haplotype sharing indicates that ecological and sexual selection are likely not strong enough to complete reproductive isolation within several species in the white-headed gull complex. This suggests that just a few genes are driving the speciation process. PMID- 27369454 TI - Rapid and recent diversification of curassows, guans, and chachalacas (Galliformes: Cracidae) out of Mesoamerica: Phylogeny inferred from mitochondrial, intron, and ultraconserved element sequences. AB - The Cracidae (curassows, guans, and chachalacas) include some of the most spectacular and endangered Neotropical bird species. They lack a comprehensive phylogenetic hypothesis, hence their geographic origin and the history of their diversification remain unclear. We present a species-level phylogeny of Cracidae inferred from a matrix of 430 ultraconserved elements (UCEs; at least one species sampled per genus) and eight more variable loci (introns and mtDNA; all available species). We use this phylogeny along with probabilistic biogeographic modeling to test whether Gondwanan vicariance, ancient dispersal to South America, ancient dispersal from South America, or massive global cooling isolated cracids in the Neotropics. Contrary to previous estimates that extant cracids diversified in the Cretaceous, our fossil-calibrated divergence time estimates instead support that crown Cracidae originated in the late Miocene. Species-rich genera Crax, Penelope, and Ortalis began diversifying as recently as 3Mya. Biogeographic reconstructions indicate that modern cracids originated in Mesoamerica and were isolated from a widespread Laurasian ancestor, consistent with the massive global cooling hypothesis. Current South American diversity is the result of multiple colonization events following uplift of the Panamanian Isthmus, coupled with rapid diversification and evolution of secondary sympatry. Of the four major cracid lineages (curassows, chachalacas, typical guans, horned guan), the only lineage that has failed to colonize and diversify South America is the unique horned guan (Oreophasis derbianus), which is sister to curassows and chachalacas rather than typical guans. PMID- 27369455 TI - Phylogenomic analyses of large-scale nuclear genes provide new insights into the evolutionary relationships within the rosids. AB - The Rosids is one of the largest groups of flowering plants, with 140 families and ~70,000 species. Previous phylogenetic studies of the rosids have primarily utilized organelle genes that likely differ in evolutionary histories from nuclear genes. To better understand the evolutionary history of rosids, it is necessary to investigate their phylogenetic relationships using nuclear genes. Here, we employed large-scale phylogenomic datasets composed of nuclear genes, including 891 clusters of putative orthologous genes. Combined with comprehensive taxon sampling covering 63 species representing 14 out of the 17 orders, we reconstructed the rosids phylogeny with coalescence and concatenation methods, yielding similar tree topologies from all datasets. However, these topologies did not agree on the placement of Zygophyllales. Through comprehensive analyses, we found that missing data and gene tree heterogeneity were potential factors that may mislead concatenation methods, in particular, large amounts of missing data under high gene tree heterogeneity. Our results provided new insights into the deep phylogenetic relationships of the rosids, and demonstrated that coalescence methods may effectively resolve the phylogenetic relationships of the rosids with missing data under high gene tree heterogeneity. PMID- 27369456 TI - A subset of fat-predominant angiomyolipomas label for MDM2: a potential diagnostic pitfall. AB - Angiomyolipomas (AMLs) are typically benign mesenchymal tumors with variable histologic composition. Fat-predominant AMLs can mimic well-differentiated liposarcomas (WDLSs) both radiographically and histologically because of the abundance of fat with admixed atypical cells resembling lipoblasts. However, the treatment and prognosis of AMLs and WDLSs are vastly different. Immunohistochemistry for murine double minute 2 (MDM2) has been used to support a diagnosis of WDLS; however, MDM2 labeling has not been specifically evaluated in fat-predominant AMLs. Here, we evaluated MDM2 immunohistochemistry in 36 AMLs (including 14 conventional AMLs, 13 fat-predominant AMLs, 6 fat-rich AMLs, 3 epithelioid AMLs) and 10 WDLSs. In addition, we labeled cases for HMB45, calponin, or actin, which are immunostains traditionally used to label AML. We performed fluorescence in situ hybridization (FISH) for MDM2 amplification on selected cases. By immunohistochemistry, 14% (5/36) of AMLs were MDM2+, including 23% (3/13) of fat-predominant AMLs. All MDM2+ AMLs evaluated by FISH (n=4) were negative for MDM2 amplification. By immunohistochemistry, 90% of WDLSs were MDM2+, and both MDM2+ WDLSs evaluated by FISH (n=2) were MDM2 amplified. All 36 AMLs labeled with HMB45 and calponin or actin. No WDLS labeled with HMB45; however, 80% of WDLSs labeled with calponin or actin. Although uncommon, MDM2 labeling is seen in a subset of fat-predominant AMLs and is a potential diagnostic pitfall in the evaluation of fatty tumors of the retroperitoneum. HMB45 is more sensitive and specific for AML than calponin or actin, and an immunopanel containing both HMB45 and MDM2 may be warranted to distinguish between fat-predominant AML and WDLS in histologically ambiguous cases. PMID- 27369457 TI - Biohydroxylation of 7-oxo-DHEA, a natural metabolite of DHEA, resulting in formation of new metabolites of potential pharmaceutical interest. AB - Metabolism of steroids in healthy and unhealthy human organs is the subject of extensive clinical and biomedical studies. For this kind of investigations, it is essential that the reference samples of new derivatives of natural, physiologically active steroids (especially those difficult to achieve in the chemical synthesis) become available. This study demonstrated for the first time transformation of 7-oxo-DHEA-a natural metabolite of DHEA, using Syncephalastrum racemosum cells. The single-pulse fermentation of substrate produced two new hydroxy metabolites: 1beta,3beta-dihydroxy-androst-5-en-7,17-dione and 3beta,12beta-dihydroxy-androst-5-en-7,17-dione, along with the earlier reported 3beta,9alpha-dihydroxy-androst-5-en-7,17-dione and 3beta,17beta-dihydroxy-androst 5-en-7-one. Simultaneously, the same metabolites, together with small quantities of 7alpha- and 7beta-hydroxy-DHEA, as well as the products of their reduction at the C-17 were obtained after transformation of DHEA under pulse-feeding of the substrate. The observed reactions suggested that this micro-organism contains enzymes exhibiting similar activity to those present in human cells. Thus, the resulting compounds can be considered as potential components of the eukaryotic, including human, metabolome. PMID- 27369458 TI - The Three-item ALERT-B Questionnaire Provides a Validated Screening Tool to Detect Chronic Gastrointestinal Symptoms after Pelvic Radiotherapy in Cancer Survivors. AB - AIMS: Although pelvic radiotherapy is an effective treatment for various malignancies, around half of patients develop significant gastrointestinal problems. These symptoms often remain undetected, despite the existence of effective treatments. This study developed and refined a simple screening tool to detect common gastrointestinal symptoms in outpatient clinics. These symptoms have a significant effect on quality of life. This tool will increase detection rates and so enable access to specialist gastroenterologists, which will in turn lead to improved symptom control and quality of life after treatment. MATERIALS AND METHODS: A literature review and expert consensus meeting identified four items for the ALERT-B (Assessment of Late Effects of RadioTherapy - Bowel) screening tool. ALERT-B was face tested for its usability and acceptability using cognitive interviews with 12 patients experiencing late gastrointestinal symptoms after pelvic radiotherapy. Thematic analysis and probe category were used to analyse interview transcripts. Interview data were presented to a group of experts to agree on the final content and format of the tool. ALERT-B was assessed for reliability and tested for validity against the Gastrointestinal Symptom Rating Scale in a clinical study (EAGLE). RESULTS: Overall, the tool was found to be acceptable in terms of wording, response format and completion time. Participant-reported experiences, including lifestyle modifications and the psychological effect of the symptoms, led to further modifications of the tool. The refined tool includes three questions covering rectal bleeding, incontinence, nocturnal bowel movements and impact on quality of life, including mood, relationships and socialising. ALERT-B was successfully validated against the Gastrointestinal Symptom Rating Scale in the EAGLE study with the tool shown broadly to be internally consistent (Cronbach's alpha = 0.61 and all item subscale correlation [Spearman] coefficients are > 0.6). CONCLUSION: The ALERT-B screening tool can be used in clinical practice to improve post-treatment supportive care by triggering the clinical assessment of patients suitable for referral to a gastroenterologist. PMID- 27369459 TI - Outcomes Following a Moderately Hypofractionated Adjuvant Radiation (START B Type) Schedule for Breast Cancer in an Unscreened Non-Caucasian Population. AB - AIMS: Breast cancer is the most common cancer in women. Western data have confirmed hypofractionated radiation therapy to be safe and effective in the adjuvant radiation therapy of breast cancers. We report the disease-related outcomes in a non-Caucasian, unscreened population treated with hypofractionated radiation. MATERIALS AND METHODS: Unselected case notes of patients presenting to a tertiary cancer centre between June 2011 and December 2013 were reviewed from the electronic hospital case records. Patients with a diagnosis of non-metastatic invasive non-sarcomatous breast cancer were identified. Demographic information, oestrogen receptor (ER), progesterone receptor (PR), HER2 status, pathological tumour, nodal stage at diagnosis and outcomes of treatment, including systemic therapies, surgery and hypofractionated radiation, were documented. Local recurrence rates, disease-free survival (DFS) and overall survival were calculated. RESULTS: Overall 925 patents were identified, median age 53.0 years (interquartile range 45-61), 330 of whom had neoadjuvant chemotherapy. The median follow-up time was 22.6 months and 23.5 months for overall and neoadjuvant chemotherapy groups, respectively. ER, PR and HER2 status was available in 788 patients, 77.2% of whom were ER/PR positive, 14.7% had triple negative disease, while 9.5% were HER2 rich. Overall, 34.2% (113 patients) underwent breast conservation surgery; 744 (80.4%) patients were treated with systemic chemotherapy and 878 (94.9%) patients received adjuvant radiation therapy, of whom 407 (44.0%) received supraclavicular-fossa radiotherapy. Overall survival, DFS and locoregional recurrence-free survival (LRRFS) for the overall group were 93%, 86.9% and 97.1%, respectively. LRRFS in the breast conservation surgery versus mastectomy groups were 99% versus 95.5% (P=0.003), with more node-positive patients in the mastectomy group. Stage N0/1 had better LRRFS compared with N2/2 (99.1% versus 95.7%); 94.3% versus 82.3%; P=0.005, 0.000. Grade 3 (53.8%) tumours had worse overall survival compared with grade 1 or grade 2 disease (89.6% versus 100% and 96.4%; P<0.001) although the LRRFS was not significantly different between the groups (98.9% versus 97.8%; P=0.37). There was no difference in LRRFS based on molecular subtypes. CONCLUSION: Local recurrence rates following hypofractionated radiation in our population were comparable with those reported by the START trialists and were found to be safe in the medium term for patients irrespective of breast conservation surgery/mastectomy or radiotherapy to the supraclavicular field. Molecular group frequencies were comparable with Western populations but did not affect LRRFS. PMID- 27369460 TI - Colonization and demographic expansion of freshwater fauna across the Hawaiian archipelago. AB - It is widely accepted that insular terrestrial biodiversity progresses with island age because colonization and diversification proceed over time. Here, we assessed whether this principle extends to oceanic island streams. We examined rangewide mtDNA sequence variation in four stream-dwelling species across the Hawaiian archipelago to characterize the relationship between colonization and demographic expansion, and to determine whether either factor reflects island age. We found that colonization and demographic expansion are not related and that neither corresponds to island age. The snail Neritina granosa exhibited the oldest colonization time (~2.713 mya) and time since demographic expansion (~282 kya), likely reflecting a preference for lotic habitats most prevalent on young islands. Conversely, gobioid fishes (Awaous stamineus, Eleotris sandwicensis and Sicyopterus stimpsoni) colonized the archipelago only ~0.411-0.935 mya, suggesting ecological opportunities for colonization in this group were temporally constrained. These findings indicate that stream communities form across colonization windows, underscoring the importance of ecological opportunities in shaping island freshwater diversity. PMID- 27369461 TI - DNA Diagnosis of Cystic Fibrosis by Direct Detection of the Af508 Mutation. AB - Cystic fibrosis (CF) is one of the most frequent recessive disorders among Caucasians. DNA analysis is perfonned by linkage analysis with DNA markers tightly linked to the CF gene. Cloning and sequencing of the cystic fibrosis gene, however, revealed ti.lat the major disease mutation is a phenylalanine deletion at amino acid position 508 of the mature protein (dF508). These recent discoveries open great perspectives for the diagnosis of cystic fibrosis and for the detection of carriers in the nonnal population. In the present study we have used the polymerase chain reaction to detect the dF508 mutation. This mutation was present on 80.3% of the CF chromosomes in the Belgian population. Twenty three of 740 nonnal individuals (3, I %) were heterozygous carriers. Therefore, the frequencyofheterozygous carriers in the Belgian population is estimated to be about 3, 9 % or I in every 26 individuals. PMID- 27369462 TI - Clinical Problem Solving Series. PMID- 27369464 TI - Additive sex-specific influence of common non-synonymous DISC1 variants on amygdala, basal ganglia, and white cortical surface area in healthy young adults. AB - The disrupted-in-schizophrenia-1 (DISC1) gene is known for its role in the development of mental disorders. It is also involved in neurodevelopment, cognition, and memory. To investigate the association between DISC1 variants and brain morphology, we analyzed the influence of the three common non-synonymous polymorphisms in DISC1 on specific brain structures in healthy young adults. The volumes of brain regions were determined in 145 subjects by magnetic resonance imaging and automated analysis using FreeSurfer. Genotyping was performed by high resolution melting of amplified products. In an additive genetic model, rs6675281 (Leu607Phe), rs3738401 (Arg264Gln), and rs821616 (Ser704Cys) significantly explained the volume variance of the amygdala (p = 0.007) and the pallidum (p = 0.004). A higher cumulative portion of minor alleles was associated with larger volumes of the amygdala (p = 0.005), the pallidum (p = 0.001), the caudate (p = 0.024), and the putamen (p = 0.007). Sex-stratified analysis revealed a strong genetic effect of rs6675281 on putamen and pallidum in females but not in males and an opposite influence of rs3738401 on the white cortical surface in females compared to males. The strongest single association was found for rs821616 and the amygdala volume in male subjects (p < 0.001). No effect was detected for the nucleus accumbens. We report-to our knowledge-for the first time a significant and sex-specific influence of common DISC1 variants on volumes of the basal ganglia, the amygdala and on the cortical surface area. Our results demonstrate that the additive model of all three polymorphisms outperforms their single analysis. PMID- 27369465 TI - Inducing theta oscillations in the entorhinal hippocampal network in vitro. AB - The hippocampal theta rhythm emerges as rhythmic and synchronized activities among the hippocampus and hippocampus-associated brain regions during active exploration, providing a potential means for inter-regional communication. However, after decades of research, the origins of the theta rhythm remain elusive, at least partly due to the difficulty in recording from all three essential regions for theta generation, namely the hippocampus itself, the septum, and the entorhinal cortex. For this reason, we established an in vitro theta model in a septo-entorhinal-hippocampal brain slice tri-culture system by pairing septal cholinergic inputs with hippocampal local activities. Our study shows that the local entorhinal cortical circuit may play an active and critical role in hippocampal theta rhythm generation. Our study also reveals a potential mechanism for theta rhythms to emerge as the functional results of dynamic interactions among the septum, hippocampus, and the entorhinal cortex, in the absence of clear pace makers. PMID- 27369466 TI - Experimental and theoretical studies of copper complexes with isomeric dipeptides as novel candidates against breast cancer. AB - In the search for new cytotoxic drugs, two copper complexes with isomeric dipeptides (Ala-Phe and Phe-Ala) were developed in order to determine the influence of their different structures in the modulation of the chemical, biochemical and biological properties. Spectroscopic, voltammetric and equilibrium studies were performed providing information about the chemical properties. The superoxide dismutase (SOD) activity was studied and showed differences of IC50 for both Cu-Ala-Phe (IC50=4.5) and Cu-Phe-Ala (IC50=45). The computational results permitted to explain this behavior proposing that it is feasible that the O2- anion is attracted straight to the positive zone in Cu-Ala Phe whereas for Cu-Phe-Ala this phenomenon would happen to a smaller extent. Confirming our previous studies, both complexes interacted with DNA. Molecular docking studies showed that the position of the phenyl ring modulates the complex DNA affinity and in Cu-Ala-Phe the docked conformation allows the copper ion to face the DNA basis, giving rise to a more stable complex-DNA adduct than for Cu Phe-Ala. In spite of the fact that Atomic Force Microscopy showed plasmid compactation and aggregation for both complexes, the image showed softer changes in the case of Cu-Ala-Phe in comparison with those produced by Cu-Phe-Ala. In order to evaluate the effect of Cu-Ala-Phe and Cu-Phe-Ala complexes against tumor cells, we have employed three aggressive metastatic breast adenocarcinoma cellular models, derived from human (MDA-MB-231 and MCF-7) and mouse (4T1) spontaneous tumors. These experiments showed that both Cu-dipeptide complexes have a similar cytotoxic effect against breast cancer cells, and lower toxicity against BJ non-tumor cells in comparison to Cisplatin. PMID- 27369467 TI - Evaluation of DNA methylation at imprinted DMRs in the spermatozoa of oligozoospermic men in association with MTHFR C677T genotype. AB - Altered DNA methylation has been previously identified in the spermatozoa of infertile men; however, the origins of these errors are poorly understood. DNA methylation is an epigenetic modification which is thought to play a fundamental role in male germline development. DNA methylation reactions rely on the cellular availability of methyl donors, which are primarily products of folate metabolism, where a key enzyme is methylenetetrahydrofolate reductase (MTHFR). The MTHFR C677T single nucleotide polymorphism (SNP) reduces enzyme activity and may potentially alter DNA methylation processes during germline development. The objective of this study was to determine whether altered DNA methylation in spermatozoa is associated with the MTHFR C677T SNP. DNA methylation was evaluated at the H19, IG-GTL2, and MEST imprinted differentially methylated regions in the spermatozoa of 53 men - 44 oligozoospermic men and nine fertile men with normal sperm parameters via bisulfite sequencing of sperm clones. The 44 infertile men were stratified by severity of oligozoospermia - three normal (>15 million spermatozoa/mL), eight moderate (5-15 million spermatozoa/mL), 23 severe (1-5 million spermatozoa/mL), and 10 very severe (<1 million spermatozoa/mL). MTHFR C677T SNP genotyping was conducted in a subset of 44 peripheral blood samples via restriction fragment length polymorphism. A total of three men - severe oligozoospermic and CT genotype - were found to be altered, which is defined as having >=50% of their clones altered, where an altered clone was in turn defined as >=50% of CpGs with incorrect DNA methylation patterns. The incidence of three altered men within the CT subgroup, however, was not significantly higher than the incidence in the CC subgroup. Taken together, altered DNA methylation in spermatozoa was not significantly associated with the MTHFR C677T SNP; however, there was a trend for higher incidence of alterations among severe oligozoospermic infertile men with CT genotypes. PMID- 27369468 TI - Ability of paramedics to perform endotracheal intubation during continuous chest compressions: a randomized cadaver study comparing Pentax AWS and Macintosh laryngoscopes. AB - OBJECTIVE: The aim of the trial was to compare the time parameters for intubation with the use of the Macintosh (MAC) laryngoscope and Pentax AWS-S100 videolaryngoscope (AWS; Pentax Corporation, Tokyo, Japan) with and without chest compression (CC) by paramedics during simulated cardiopulmonary resuscitation in a cadaver model. METHODS: This was a randomized crossover cadaver trial. Thirty five paramedics with no experience in videolaryngoscopy participated in the study. They performed intubation in two emergency scenarios: scenario A, normal airway without CC; scenario B, normal airway with continuous CC. RESULTS: The median time to first ventilation with the use of the AWS and the MAC was similar in scenario A: 25 (IQR, 22-27) seconds vs. 24 (IQR, 22.5-26) seconds (P=.072). A statistically significant difference in TTFV between AWS and MAC was noticed in scenario B (P=.011). In scenario A, the first endotracheal intubation (ETI) attempt success rate was achieved in 97.1% with AWS compared with 94.3% with MAC (P=.43). In scenario B, the success rate after the first ETI attempt with the use of the different intubation methods varied and amounted to 88.6% vs. 77.1% for AWS and MAC, respectively (P=.002). CONCLUSIONS: The Pentax AWS offered a superior glottic view as compared with the MAC laryngoscope, which was associated with a higher intubation rate and a shorter intubation time during an uninterrupted CC scenario. However, in the scenario without CC, the results for AWS and MAC were comparable. PMID- 27369470 TI - Incentivizing Patient Choices: The Ethics of Inclusive Shared Savings. AB - Is it ethical to pay patients for selecting cheaper medical treatments? The healthcare system in the United States is notoriously profligate, at least in part because when insurers foot the bill, patients have little incentive to avoid wasteful treatments. One familiar means for dealing with this problem is for insurers to offer reduced co-pays to patients who select cheaper treatments. Would it be ethical to take this one step further, beyond the zero bound, sharing the savings of cheaper treatments by positively paying the patients who select them? Schmidt & Emanuel recently proposed this policy of 'Inclusive Shared Savings' (ISS). This article examines various ethical objections to the idea. PMID- 27369469 TI - Ingestion of the epoxide hydrolase inhibitor AUDA modulates immune responses of the mosquito, Culex quinquefasciatus during blood feeding. AB - Epoxide hydrolases (EHs) are enzymes that play roles in metabolizing xenobiotic epoxides from the environment, and in regulating lipid signaling molecules, such as juvenile hormones in insects and epoxy fatty acids in mammals. In this study we fed mosquitoes with an epoxide hydrolase inhibitor AUDA during artificial blood feeding, and we found the inhibitor increased the concentration of epoxy fatty acids in the midgut of female mosquitoes. We also observed ingestion of AUDA triggered early expression of defensin A, cecropin A and cecropin B2 at 6 h after blood feeding. The expression of cecropin B1 and gambicin were not changed more than two fold compared to controls. The changes in gene expression were transient possibly because more than 99% of the inhibitor was metabolized or excreted at 42 h after being ingested. The ingestion of AUDA also affected the growth of bacteria colonizing in the midgut, but did not affect mosquito longevity, fecundity and fertility in our laboratory conditions. When spiked into the blood, EpOMEs and DiHOMEs were as effective as the inhibitor AUDA in reducing the bacterial load in the midgut, while EETs rescued the effects of AUDA. Our data suggest that epoxy fatty acids from host blood are immune response regulators metabolized by epoxide hydrolases in the midgut of female mosquitoes, inhibition of which causes transient changes in immune responses, and affects growth of microbes in the midgut. PMID- 27369471 TI - The Relationship of Intellectual Functioning and Cognitive Performance to Brain Structure in Schizophrenia. AB - Background: Schizophrenia (SZ) is often characterized by cognitive and intellectual impairment. However, there is much heterogeneity across individuals, suggesting different trajectories of the illness. Recent findings have shown brain volume differences across subgroups of individuals with psychosis (SZ and bipolar disorder), such that those with intellectual and cognitive impairments presented evidence of early cerebral disruption, while those with cognitive but not intellectual impairments showed evidence of progressive brain abnormalities. Our aim was to investigate the relations of cognition and intellectual functioning with brain structure abnormalities in a sample of SZ compared to unaffected individuals. Methods: 92 individuals with SZ and 94 healthy controls part of the Northwestern University Schizophrenia Data and Software Tool (NUSDAST) underwent neuropsychological assessment and structural magnetic resonance imaging (MRI). Individuals with SZ were divided into subgroups according their estimated premorbid crystallized intellectual (ePMC-IQ) and cognitive performance. Brain volumes differences were investigated across groups. Results: SZ with ePMC-IQ and cognitive impairments had reduced total brain volume (TBV), intracranial volume (ICV), TBV corrected for ICV, and cortical gray matter volume, as well as reduced cortical thickness, and insula volumes. SZ with cognitive impairment but intact ePMC-IQ showed only reduced cortical gray matter volume and cortical thickness. Conclusions: These data provide additional evidence for heterogeneity in SZ. Impairments in cognition associated with reduced ePMC-IQ were related to evidence of broad brain structural alterations, including suggestion of early cerebral disruption. In contrast, impaired cognitive functioning in the context of more intact intellectual functioning was associated with cortical alterations that may reflect neurodegeneration. PMID- 27369473 TI - Why do we need a social psychiatry? AB - Human beings are social animals, and familial or social relationships can cause a variety of difficulties as well as providing support in our social functioning. The traditional way of looking at mental illness has focused on abnormal thoughts, actions and behaviours in response to internal causes (such as biological factors) as well as external ones such as social determinants and social stressors. We contend that psychiatry is social. Mental illness and interventions in psychiatry should be considered in the framework of social context where patients live and factors they face on a daily basis. PMID- 27369474 TI - Global mental health in high-income countries. AB - Over the past decade there have been significant efforts to scale-up mental health services in resource-poor countries. A number of cost-effective innovations have emerged as a result. At the same time, there is increasing concern in resource-rich countries about efficacy, efficiency and acceptability of mental health services. We consider two specific innovations used widely in low- and middle-income countries, task-sharing and a development model of mental healthcare, that we believe have the potential to address some of the current challenges facing mental health services in high-income countries. PMID- 27369472 TI - Neuroanatomical Predictors of Functional Outcome in Individuals at Ultra-High Risk for Psychosis. AB - Most individuals at ultra-high risk (UHR) for psychosis do not transition to frank illness. Nevertheless, many have poor clinical outcomes and impaired psychosocial functioning. This study used voxel-based morphometry to investigate if baseline grey and white matter brain densities at identification as UHR were associated with functional outcome at medium- to long-term follow-up. Participants were help-seeking UHR individuals (n = 109, 54M:55F) who underwent magnetic resonance imaging at baseline; functional outcome was assessed an average of 9.2 years later. Primary analysis showed that lower baseline grey matter density, but not white matter density, in bilateral frontal and limbic areas, and left cerebellar declive were associated with poorer functional outcome (Social and Occupational Functioning Assessment Scale [SOFAS]). These findings were independent of transition to psychosis or persistence of the at-risk mental state. Similar regions were significantly associated with lower self-reported levels of social functioning and increased negative symptoms at follow-up. Exploratory analyses showed that lower baseline grey matter densities in middle and inferior frontal gyri were significantly associated with decline in Global Assessment of Functioning (GAF) score over follow-up. There was no association between baseline grey matter density and IQ or positive symptoms at follow-up. The current findings provide novel evidence that those with the poorest functional outcomes have the lowest grey matter densities at identification as UHR, regardless of transition status or persistence of the at-risk mental state. Replication and validation of these findings may allow for early identification of poor functional outcome and targeted interventions. PMID- 27369475 TI - Negative results in phase III trials of complex interventions: cause for concern or just good science? AB - Not all interventions that show promise in exploratory trials will be supported in phase III studies. But the high failure rate in recent trials of complex mental health interventions is a concern. Proper consideration of trial processes and greater use of adaptive trial designs could ensure better use of available resources. PMID- 27369480 TI - Dr Peter Mark Roget (1779-1869) - psychiatry in history. PMID- 27369477 TI - Service user, patient, survivor or client ... has the time come to return to 'patient'? AB - Recently, the Council of the UK Royal College of Psychiatrists agreed to use the term 'patient' as the preferred collective noun when referring to people accessing mental health services in its official documentation. Choices regarding terminology have the power to influence those who use such terms and here, David Christmas and Angela Sweeney debate the issue of whether such a decision is appropriate or whether we need to be more careful about the terms we use. PMID- 27369481 TI - ECT, cognitive function and neuropsychological testing. PMID- 27369482 TI - Authors' reply. PMID- 27369483 TI - Defining clinically significant change. PMID- 27369484 TI - Authors' reply. PMID- 27369489 TI - Communication: Proton NMR dipolar-correlation effect as a method for investigating segmental diffusion in polymer melts. AB - A simple and fast method for the investigation of segmental diffusion in high molar mass polymer melts is presented. The method is based on a special function, called proton dipolar-correlation build-up function, which is constructed from Hahn Echo signals measured at times t and t/2. The initial rise of this function contains additive contributions from both inter- and intramolecular magnetic dipole-dipole interactions. The intermolecular contribution depends on the relative mean squared displacements (MSDs) of polymer segments from different macromolecules, while the intramolecular part reflects segmental reorientations. Separation of both contributions via isotope dilution provides access to segmental displacements in polymer melts at millisecond range, which is hardly accessible by other methods. The feasibility of the method is illustrated by investigating protonated and deuterated polybutadiene melts with molecular mass 196 000 g/mol at different temperatures. The observed exponent of the power law of the segmental MSD is close to 0.32 +/- 0.03 at times when the root MSD is in between 45 A and 75 A, and the intermolecular proton dipole-dipole contribution to the total proton Hahn Echo NMR signal is larger than 50% and increases with time. PMID- 27369488 TI - Rationale and design of the Baptist Employee Healthy Heart Study: a randomized trial assessing the efficacy of the addition of an interactive, personalized, web based, lifestyle intervention tool to an existing health information web platform in a high-risk employee population. AB - BACKGROUND: Metabolic syndrome (MetS) and diabetes confer a high risk for developing subsequent cardiovascular disease (CVD). Persons with MetS constitute 24-34 % of the employee population at Baptist Health South Florida (BHSF), a self insured healthcare organization. The Baptist Employee Healthy Heart Study (BEHHS) aims to assess the addition of a personalized, interactive, web-based, nutrition management and lifestyle-management program to the existing health-expertise web platform available to BHSF employees in reducing and/or stabilizing CVD and lifestyle risk factors and markers of subclinical CVD. METHODS/DESIGN: Subjects with MetS or Type II Diabetes will be recruited from an employee population at BHSF and randomized to either an intervention or a control arm. The intervention arm will be given access to a web-based personalized diet-modification and weight modification program. The control arm will be reminded to use the standard informational health website available and accessible to all BHSF employees. Subjects will undergo coronary calcium testing, carotid intima-media thickness scans, peripheral arterial tonometry, and advanced lipid panel testing at visit 1, in addition to lifestyle and medical history questionnaires. All tests will be repeated at visits 2 and 4 with the exception of the coronary calcium test, which will only be performed at baseline and visit 4. Visit 3 will capture vitals, anthropometrics, and responses to the questionnaires only. CONCLUSION: Results of this study will provide information on the effectiveness of personalized, web based, lifestyle-management tools in reducing healthcare costs, promoting healthy choices, and reducing cardiovascular risk in an employee population. It will also provide information about the natural history of carotid atherosclerosis and endothelial dysfunction in asymptomatic but high-risk populations. TRIAL REGISTRATION: ClinicalTrials.gov registry, NCT01912209 . Registered on 3 July 2013. PMID- 27369490 TI - Communication: Visualization and spectroscopy of defects induced by dehydrogenation in individual silicon nanocrystals. AB - We present results of a scanning tunneling spectroscopy (STS) study of the impact of dehydrogenation on the electronic structures of hydrogen-passivated silicon nanocrystals (SiNCs) supported on the Au(111) surface. Gradual dehydrogenation is achieved by injecting high-energy electrons into individual SiNCs, which results, initially, in reduction of the electronic bandgap, and eventually produces midgap electronic states. We use theoretical calculations to show that the STS spectra of midgap states are consistent with the presence of silicon dangling bonds, which are found in different charge states. Our calculations also suggest that the observed initial reduction of the electronic bandgap is attributable to the SiNC surface reconstruction induced by conversion of surface dihydrides to monohydrides due to hydrogen desorption. Our results thus provide the first visualization of the SiNC electronic structure evolution induced by dehydrogenation and provide direct evidence for the existence of diverse dangling bond states on the SiNC surfaces. PMID- 27369491 TI - Dissipative particle dynamics of diffusion-NMR requires high Schmidt-numbers. AB - We present an efficient mesoscale model to simulate the diffusion measurement with nuclear magnetic resonance (NMR). On the level of mesoscopic thermal motion of fluid particles, we couple the Bloch equations with dissipative particle dynamics (DPD). Thereby we establish a physically consistent scaling relation between the diffusion constant measured for DPD-particles and the diffusion constant of a real fluid. The latter is based on a splitting into a centre-of mass contribution represented by DPD, and an internal contribution which is not resolved in the DPD-level of description. As a consequence, simulating the centre of-mass contribution with DPD requires high Schmidt numbers. After a verification for fundamental pulse sequences, we apply the NMR-DPD method to NMR diffusion measurements of anisotropic fluids, and of fluids restricted by walls of microfluidic channels. For the latter, the free diffusion and the localisation regime are considered. PMID- 27369492 TI - Tensor representation techniques for full configuration interaction: A Fock space approach using the canonical product format. AB - In this proof-of-principle study, we apply tensor decomposition techniques to the Full Configuration Interaction (FCI) wavefunction in order to approximate the wavefunction parameters efficiently and to reduce the overall computational effort. For this purpose, the wavefunction ansatz is formulated in an occupation number vector representation that ensures antisymmetry. If the canonical product format tensor decomposition is then applied, the Hamiltonian and the wavefunction can be cast into a multilinear product form. As a consequence, the number of wavefunction parameters does not scale to the power of the number of particles (or orbitals) but depends on the rank of the approximation and linearly on the number of particles. The degree of approximation can be controlled by a single threshold for the rank reduction procedure required in the algorithm. We demonstrate that using this approximation, the FCI Hamiltonian matrix can be stored with N(5) scaling. The error of the approximation that is introduced is below Millihartree for a threshold of epsilon = 10(-4) and no convergence problems are observed solving the FCI equations iteratively in the new format. While promising conceptually, all effort of the algorithm is shifted to the required rank reduction procedure after the contraction of the Hamiltonian with the coefficient tensor. At the current state, this crucial step is the bottleneck of our approach and even for an optimistic estimate, the algorithm scales beyond N(10) and future work has to be directed towards reduction-free algorithms. PMID- 27369493 TI - On the existence of the optimal order for wavefunction extrapolation in Born Oppenheimer molecular dynamics. AB - Wavefunction extrapolation greatly reduces the number of self-consistent field (SCF) iterations and thus the overall computational cost of Born-Oppenheimer molecular dynamics (BOMD) that is based on the Kohn-Sham density functional theory. Going against the intuition that the higher order of extrapolation possesses a better accuracy, we demonstrate, from both theoretical and numerical perspectives, that the extrapolation accuracy firstly increases and then decreases with respect to the order, and an optimal extrapolation order in terms of minimal number of SCF iterations always exists. We also prove that the optimal order tends to be larger when using larger MD time steps or more strict SCF convergence criteria. By example BOMD simulations of a solid copper system, we show that the optimal extrapolation order covers a broad range when varying the MD time step or the SCF convergence criterion. Therefore, we suggest the necessity for BOMD simulation packages to open the user interface and to provide more choices on the extrapolation order. Another factor that may influence the extrapolation accuracy is the alignment scheme that eliminates the discontinuity in the wavefunctions with respect to the atomic or cell variables. We prove the equivalence between the two existing schemes, thus the implementation of either of them does not lead to essential difference in the extrapolation accuracy. PMID- 27369494 TI - The electron localization as the information content of the conditional pair density. AB - In the present work, the information gained by an electron for "knowing" about the position of another electron with the same spin is calculated using the Kullback-Leibler divergence (DKL) between the same-spin conditional pair probability density and the marginal probability. DKL is proposed as an electron localization measurement, based on the observation that regions of the space with high information gain can be associated with strong correlated localized electrons. Taking into consideration the scaling of DKL with the number of sigma spin electrons of a system (N(sigma)), the quantity chi = (N(sigma) - 1) DKLfcut is introduced as a general descriptor that allows the quantification of the electron localization in the space. fcut is defined such that it goes smoothly to zero for negligible densities. chi is computed for a selection of atomic and molecular systems in order to test its capability to determine the region in space where electrons are localized. As a general conclusion, chi is able to explain the electron structure of molecules on the basis of chemical grounds with a high degree of success and to produce a clear differentiation of the localization of electrons that can be traced to the fluctuation in the average number of electrons in these regions. PMID- 27369495 TI - Non-Condon equilibrium Fermi's golden rule electronic transition rate constants via the linearized semiclassical method. AB - In this paper, we test the accuracy of the linearized semiclassical (LSC) expression for the equilibrium Fermi's golden rule rate constant for electronic transitions in the presence of non-Condon effects. We do so by performing a comparison with the exact quantum-mechanical result for a model where the donor and acceptor potential energy surfaces are parabolic and identical except for shifts in the equilibrium energy and geometry, and the coupling between them is linear in the nuclear coordinates. Since non-Condon effects may or may not give rise to conical intersections, both possibilities are examined by considering: (1) A modified Garg-Onuchic-Ambegaokar model for charge transfer in the condensed phase, where the donor-acceptor coupling is linear in the primary mode coordinate, and for which non-Condon effects do not give rise to a conical intersection; (2) the linear vibronic coupling model for electronic transitions in gas phase molecules, where non-Condon effects give rise to conical intersections. We also present a comprehensive comparison between the linearized semiclassical expression and a progression of more approximate expressions. The comparison is performed over a wide range of frictions and temperatures for model (1) and over a wide range of temperatures for model (2). The linearized semiclassical method is found to reproduce the exact quantum-mechanical result remarkably well for both models over the entire range of parameters under consideration. In contrast, more approximate expressions are observed to deviate considerably from the exact result in some regions of parameter space. PMID- 27369496 TI - Simulation of optical response functions in molecular junctions. AB - We discuss theoretical approaches to nonlinear optical spectroscopy of molecular junctions. Optical response functions are derived in a form convenient for the implementation of Green function techniques, and their expressions in terms of pseudoparticle nonequilibrium Green functions are proposed. The formulation allows to account for both intramolecular interactions and hybridization of molecular states with those of contacts. Within a generic model and utilizing two dimensional optical spectroscopy as an example, the methodology is compared with exact simulations and is shown to work where the traditional Liouville space approach fails. PMID- 27369497 TI - Exits in order: How crowding affects particle lifetimes. AB - Diffusive processes are often represented using stochastic random walk frameworks. The amount of time taken for an individual in a random walk to intersect with an absorbing boundary is a fundamental property that is often referred to as the particle lifetime, or the first passage time. The mean lifetime of particles in a random walk model of diffusion is related to the amount of time required for the diffusive process to reach a steady state. Mathematical analysis describing the mean lifetime of particles in a standard model of diffusion without crowding is well known. However, the lifetime of agents in a random walk with crowding has received much less attention. Since many applications of diffusion in biology and biophysics include crowding effects, here we study a discrete model of diffusion that incorporates crowding. Using simulations, we show that crowding has a dramatic effect on agent lifetimes, and we derive an approximate expression for the mean agent lifetime that includes crowding effects. Our expression matches simulation results very well, and highlights the importance of crowding effects that are sometimes overlooked. PMID- 27369498 TI - Quantum dynamics of incoherently driven V-type systems: Analytic solutions beyond the secular approximation. AB - Closed-form analytic solutions to non-secular Bloch-Redfield master equations for quantum dynamics of a V-type system driven by weak coupling to a thermal bath, relevant to light harvesting processes, are obtained and discussed. We focus on noise-induced Fano coherences among the excited states induced by incoherent driving of the V-system initially in the ground state. For suddenly turned-on incoherent driving, the time evolution of the coherences is determined by the damping parameter zeta=12(gamma1+gamma2)/Deltap, where gammai are the radiative decay rates of the excited levels i = 1, 2, and Deltap=Delta(2)+(1 p(2))gamma1gamma2 depends on the excited-state level splitting Delta > 0 and the angle between the transition dipole moments in the energy basis. The coherences oscillate as a function of time in the underdamped limit (zeta ? 1), approach a long-lived quasi-steady state in the overdamped limit (zeta ? 1), and display an intermediate behavior at critical damping (zeta = 1). The sudden incoherent turn on is shown to generate a mixture of excited eigenstates |e1> and |e2> and their in-phase coherent superposition |phi+>=1r1+r2(r1|e1>+r2|e2>), which is remarkably long-lived in the overdamped limit (where r1 and r2 are the incoherent pumping rates). Formation of this coherent superposition enhances the decay rate from the excited states to the ground state. In the strongly asymmetric V-system where the coupling strengths between the ground state and the excited states differ significantly, additional asymptotic quasistationary coherences are identified, which arise due to slow equilibration of one of the excited states. Finally, we demonstrate that noise-induced Fano coherences are maximized with respect to populations when r1 = r2 and the transition dipole moments are fully aligned. PMID- 27369499 TI - Accelerating ring-polymer molecular dynamics with parallel-replica dynamics. AB - Nuclear quantum effects are important for systems containing light elements, and the effects are more prominent in the low temperature regime where the dynamics also becomes sluggish. We show that parallel replica (ParRep) dynamics, an accelerated molecular dynamics approach for infrequent-event systems, can be effectively combined with ring-polymer molecular dynamics, a semiclassical trajectory approach that gives a good approximation to zero-point and tunneling effects in activated escape processes. The resulting RP-ParRep method is a powerful tool for reaching long time scales in complex infrequent-event systems where quantum dynamics are important. Two illustrative examples, symmetric Eckart barrier crossing and interstitial helium diffusion in Fe and Fe-Cr alloy, are presented to demonstrate the accuracy and long-time scale capability of this approach. PMID- 27369500 TI - Hubbard physics in the PAW GW approximation. AB - It is demonstrated that the signatures of the Hubbard Model in the strongly interacting regime can be simulated by modifying the screening in the limit of zero wavevector in Projector-Augmented Wave GW calculations for systems without significant nesting. This modification, when applied to the Mott insulator CuO, results in the opening of the Mott gap by the splitting of states at the Fermi level into upper and lower Hubbard bands, and exhibits a giant transfer of spectral weight upon electron doping. The method is also employed to clearly illustrate that the M1 and M2 forms of vanadium dioxide are fundamentally different types of insulator. Standard GW calculations are sufficient to open a gap in M1 VO2, which arise from the Peierls pairing filling the valence band, creating homopolar bonds. The valence band wavefunctions are stabilized with respect to the conduction band, reducing polarizability and pushing the conduction band eigenvalues to higher energy. The M2 structure, however, opens a gap from strong on-site interactions; it is a Mott insulator. PMID- 27369501 TI - A minimalistic approach to static and dynamic electron correlations: Amending generalized valence bond method with extended random phase approximation correlation correction. AB - A perfect-pairing generalized valence bond (GVB) approximation is known to be one of the simplest approximations, which allows one to capture the essence of static correlation in molecular systems. In spite of its attractive feature of being relatively computationally efficient, this approximation misses a large portion of dynamic correlation and does not offer sufficient accuracy to be generally useful for studying electronic structure of molecules. We propose to correct the GVB model and alleviate some of its deficiencies by amending it with the correlation energy correction derived from the recently formulated extended random phase approximation (ERPA). On the examples of systems of diverse electronic structures, we show that the resulting ERPA-GVB method greatly improves upon the GVB model. ERPA-GVB recovers most of the electron correlation and it yields energy barrier heights of excellent accuracy. Thanks to a balanced treatment of static and dynamic correlation, ERPA-GVB stays reliable when one moves from systems dominated by dynamic electron correlation to those for which the static correlation comes into play. PMID- 27369502 TI - Interpolation of property-values between electron numbers is inconsistent with ensemble averaging. AB - In this work we explore the physical foundations of models that study the variation of the ground state energy with respect to the number of electrons (E vs. N models), in terms of general grand-canonical (GC) ensemble formulations. In particular, we focus on E vs. N models that interpolate the energy between states with integer number of electrons. We show that if the interpolation of the energy corresponds to a GC ensemble, it is not differentiable. Conversely, if the interpolation is smooth, then it cannot be formulated as any GC ensemble. This proves that interpolation of electronic properties between integer electron numbers is inconsistent with any form of ensemble averaging. This emphasizes the role of derivative discontinuities and the critical role of a subsystem's surroundings in determining its properties. PMID- 27369503 TI - Quantum Monte Carlo with variable spins. AB - We investigate the inclusion of variable spins in electronic structure quantum Monte Carlo, with a focus on diffusion Monte Carlo with Hamiltonians that include spin-orbit interactions. Following our previous introduction of fixed-phase spin orbit diffusion Monte Carlo, we thoroughly discuss the details of the method and elaborate upon its technicalities. We present a proof for an upper-bound property for complex nonlocal operators, which allows for the implementation of T-moves to ensure the variational property. We discuss the time step biases associated with our particular choice of spin representation. Applications of the method are also presented for atomic and molecular systems. We calculate the binding energies and geometry of the PbH and Sn2 molecules, as well as the electron affinities of the 6p row elements in close agreement with experiments. PMID- 27369504 TI - On the widths of Stokes lines in Raman scattering from molecules adsorbed at metal surfaces and in molecular conduction junctions. AB - Within a generic model we analyze the Stokes linewidth in surface enhanced Raman scattering (SERS) from molecules embedded as bridges in molecular junctions. We identify four main contributions to the off-resonant Stokes signal and show that under zero voltage bias (a situation pertaining also to standard SERS experiments) and at low bias junctions only one of these contributions is pronounced. The linewidth of this component is determined by the molecular vibrational relaxation rate, which is dominated by interactions with the essentially bosonic thermal environment when the relevant molecular electronic energy is far from the metal(s) Fermi energy(ies). It increases when the molecular electronic level is close to the metal Fermi level so that an additional vibrational relaxation channel due to electron-hole (eh) exciton in the molecule opens. Other contributions to the Raman signal, of considerably broader linewidths, can become important at larger junction bias. PMID- 27369505 TI - Assessing the utility of phase-space-localized basis functions: Exploiting direct product structure and a new basis function selection procedure. AB - In this paper we show that it is possible to use an iterative eigensolver in conjunction with Halverson and Poirier's symmetrized Gaussian (SG) basis [T. Halverson and B. Poirier, J. Chem. Phys. 137, 224101 (2012)] to compute accurate vibrational energy levels of molecules with as many as five atoms. This is done, without storing and manipulating large matrices, by solving a regular eigenvalue problem that makes it possible to exploit direct-product structure. These ideas are combined with a new procedure for selecting which basis functions to use. The SG basis we work with is orders of magnitude smaller than the basis made by using a classical energy criterion. We find significant convergence errors in previous calculations with SG bases. For sum-of-product Hamiltonians, SG bases large enough to compute accurate levels are orders of magnitude larger than even simple pruned bases composed of products of harmonic oscillator functions. PMID- 27369506 TI - Rate constants of chemical reactions from semiclassical transition state theory in full and one dimension. AB - Semiclassical Transition State Theory (SCTST), a method for calculating rate constants of chemical reactions, offers gains in computational efficiency relative to more accurate quantum scattering methods. In full-dimensional (FD) SCTST, reaction probabilities are calculated from third and fourth potential derivatives along all vibrational degrees of freedom. However, the computational cost of FD SCTST scales unfavorably with system size, which prohibits its application to larger systems. In this study, the accuracy and efficiency of 1-D SCTST, in which only third and fourth derivatives along the reaction mode are used, are investigated in comparison to those of FD SCTST. Potential derivatives are obtained from numerical ab initio Hessian matrix calculations at the MP2/cc pVTZ level of theory, and Richardson extrapolation is applied to improve the accuracy of these derivatives. Reaction barriers are calculated at the CCSD(T)/cc pVTZ level. Results from FD SCTST agree with results from previous theoretical and experimental studies when Richardson extrapolation is applied. Results from our implementation of 1-D SCTST, which uses only 4 single-point MP2/cc-pVTZ energy calculations in addition to those for conventional TST, agree with FD results to within a factor of 5 at 250 K. This degree of agreement and the efficiency of the 1-D method suggest its potential as a means of approximating rate constants for systems too large for existing quantum scattering methods. PMID- 27369507 TI - Singlet-paired coupled cluster theory for open shells. AB - Restricted single-reference coupled cluster theory truncated to single and double excitations accurately describes weakly correlated systems, but often breaks down in the presence of static or strong correlation. Good coupled cluster energies in the presence of degeneracies can be obtained by using a symmetry-broken reference, such as unrestricted Hartree-Fock, but at the cost of good quantum numbers. A large body of work has shown that modifying the coupled cluster ansatz allows for the treatment of strong correlation within a single-reference, symmetry-adapted framework. The recently introduced singlet-paired coupled cluster doubles (CCD0) method is one such model, which recovers correct behavior for strong correlation without requiring symmetry breaking in the reference. Here, we extend singlet-paired coupled cluster for application to open shells via restricted open-shell singlet-paired coupled cluster singles and doubles (ROCCSD0). The ROCCSD0 approach retains the benefits of standard coupled cluster theory and recovers correct behavior for strongly correlated, open-shell systems using a spin-preserving ROHF reference. PMID- 27369508 TI - Double resonant absorption measurement of acetylene symmetric vibrational states probed with cavity ring down spectroscopy. AB - A novel mid-infrared/near-infrared double resonant absorption setup for studying infrared-inactive vibrational states is presented. A strong vibrational transition in the mid-infrared region is excited using an idler beam from a singly resonant continuous-wave optical parametric oscillator, to populate an intermediate vibrational state. High output power of the optical parametric oscillator and the strength of the mid-infrared transition result in efficient population transfer to the intermediate state, which allows measuring secondary transitions from this state with a high signal-to-noise ratio. A secondary, near infrared transition from the intermediate state is probed using cavity ring-down spectroscopy, which provides high sensitivity in this wavelength region. Due to the narrow linewidths of the excitation sources, the rovibrational lines of the secondary transition are measured with sub-Doppler resolution. The setup is used to access a previously unreported symmetric vibrational state of acetylene, nu1+nu2+nu3+nu4 (1)+nu5 (-1) in the normal mode notation. Single-photon transitions to this state from the vibrational ground state are forbidden. Ten lines of the newly measured state are observed and fitted with the linear least squares method to extract the band parameters. The vibrational term value was measured to be at 9775.0018(45) cm(-1), the rotational parameter B was 1.162 222(37) cm(-1), and the quartic centrifugal distortion parameter D was 3.998(62) * 10(-6) cm(-1), where the numbers in the parenthesis are one-standard errors in the least significant digits. PMID- 27369509 TI - A new set of potential energy surfaces for HCO: Influence of Renner-Teller coupling on the bound and resonance vibrational states. AB - It is commonly understood that the Renner-Teller effect can strongly influence the spectroscopy of molecules through coupling of electronic states. Here we investigate the vibrational bound states and low-lying resonances of the formyl radical treating the Renner-Teller coupled X(2)A(') and A(2)A(") states using the MultiConfiguration Time Dependent Hartree (MCTDH) method. The calculations were performed using the improved relaxation method for the bound states and a recently published extension to compute resonances. A new set of accurate global potential energy surfaces were computed at the explicitly correlated multireference configuration interaction (MRCI-F12) level and yielded remarkably close agreement with experiment in this application and thus enable future studies including photodissociation and collisional dynamics. The results show the necessity of including the large contribution from a Davidson correction in the electronic structure calculations in order to appreciate the relatively small effect of the Renner-Teller coupling on the states considered here. PMID- 27369510 TI - Microhydration of LiOH: Insight from electronic decays of core-ionized states. AB - We compute and compare the autoionization spectra of a core-ionized LiOH molecule both in its isolated and microhydrated states. Stepwise microhydration of LiOH leads to gradual elongation of the Li-OH bond length and finally to molecular dissociation. The accompanying changes in the local environment of the OH(-) and Li(+) counterions are reflected in the computed O 1s and Li 1s spectra. The role of solvent water molecules and the counterion in the spectral shape formation is assessed. Electronic decays of the microhydrated LiOH are found to be mostly intermolecular since the majority of the populated final states have at least one outer-valence vacancy outside the initially core-ionized ion, mainly on a neighboring water molecule. The charge delocalization occurs through the intermolecular Coulombic and electron transfer mediated decays. Both mechanisms are highly efficient that is partly attributed to hybridization of molecular orbitals. The computed spectral shapes are sensitive to the counterion separation as well as to the number and arrangement of solvent molecules. These sensitivities can be used for studying the local hydration structure of solvated ions in aqueous solutions. PMID- 27369511 TI - Star-like superalkali cations featuring planar pentacoordinate carbon. AB - Superalkali cations, known to possess low vertical electron affinities (VEAs), high vertical detachment energies, and large highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) energy gaps, are intriguing chemical species. Thermodynamically, such species need to be the global minima in order to serve as the promising targets for experimental realization. In this work, we propose the strategies of polyhalogenation and polyalkalination for designing the superalkali cations. By applying these strategies, the local minimum planar pentacoordinate carbon (ppC) cluster CBe5 can be modified to form a series of star-like superalkali ppC or quasi-ppC CBe5X5 (+) (X = F, Cl, Br, Li, Na, K) cations containing a CBe5 moiety. Polyhalogenation and polyalkalination on the CBe5 unit may help eliminate the high reactivity of bare CBe5 molecule by covering the reactive Be atoms with noble halogen anions and alkali cations. Computational exploration of the potential energy surfaces reveals that the star like ppC or quasi-ppC CBe5X5 (+) (X = F, Cl, Br, Li, Na, K) clusters are the true global minima of the systems. The predicted VEAs for CBe5X5 (+) range from 3.01 to 3.71 eV for X = F, Cl, Br and 2.12-2.51 eV for X = Li, Na, K, being below the lower bound of the atomic ionization potential of 3.89 eV in the periodic table. Large HOMO-LUMO energy gaps are also revealed for the species: 10.76-11.07 eV for X = F, Cl, Br and 4.99-6.91 eV for X = Li, Na, K. These designer clusters represent the first series of superalkali cations with a ppC center. Bonding analyses show five Be-X-Be three-center two-electron (3c-2e) sigma bonds for the peripheral bonding, whereas the central C atom is associated with one 6c-2e pi bond and three 6c-2e sigma bonds, rendering (pi and sigma) double aromaticity. Born-Oppenheimer molecular dynamics simulations indicate that the CBe5 motif is robust in the clusters. As planar hypercoordination carbon species are often thermodynamically unstable and highly reactive, the superalkali cation characters of these ppC species should be highlighted, which may be suitable for experimental realization. PMID- 27369512 TI - Detection and characterization of singly deuterated silylene, SiHD, via optical spectroscopy. AB - Singly deuterated silylene has been detected and characterized in the gas-phase using high-resolution, two-dimensional, optical spectroscopy. Rotationally resolved lines in the 00 (0)X(1)A(')->A(1)A(") band are assigned to both c-type perpendicular transition and additional parallel, axis-switching induced bands. The extracted rotational constants were combined with those for SiH2 and SiD2 to determine an improved equilibrium bond length, rSiH, and bond angle, theta, of 1.5137 +/- 0.0003 A and 92.04 degrees +/- 0.05 degrees , and 1.4853 +/- 0.0005 A and 122.48 degrees +/- 0.08 degrees for the X(1)A(')0,0,0 and A(1)A(")(0,0,0) state respectively. The dispersed fluorescence consists of a long progression in the A(1)A(")(0,0,0)->X(1)A(')(0,nu2,0) emission which was analyzed to produce vibrational parameters. A strong quantum level dependence of the rotationally resolved radiative decay curves is analyzed. PMID- 27369513 TI - Gas phase structures and charge localization in small aluminum oxide anions: Infrared photodissociation spectroscopy and electronic structure calculations. AB - We use cryogenic ion trap vibrational spectroscopy in combination with quantum chemical calculations to study the structure of mono- and dialuminum oxide anions. The infrared photodissociation spectra of D2-tagged AlO1-4 (-) and Al2O3 6 (-) are measured in the region from 400 to 1200 cm(-1). Structures are assigned based on a comparison to simulated harmonic and anharmonic IR spectra derived from electronic structure calculations. The monoaluminum anions contain an even number of electrons and exhibit an electronic closed-shell ground state. The Al2O3-6 (-) anions are oxygen-centered radicals. As a result of a delicate balance between localization and delocalization of the unpaired electron, only the BHLYP functional is able to qualitatively describe the observed IR spectra of all species with the exception of AlO3 (-). Terminal Al-O stretching modes are found between 1140 and 960 cm(-1). Superoxo and peroxo stretching modes are found at higher (1120-1010 cm(-1)) and lower energies (850-570 cm(-1)), respectively. Four modes in-between 910 and 530 cm(-1) represent the IR fingerprint of the common structural motif of dialuminum oxide anions, an asymmetric four-member Al (O)2-Al ring. PMID- 27369515 TI - Non-resonant dynamic stark control of vibrational motion with optimized laser pulses. AB - The term dynamic Stark control (DSC) has been used to describe methods of quantum control related to the dynamic Stark effect, i.e., a time-dependent distortion of energy levels. Here, we employ analytical models that present clear and concise interpretations of the principles behind DSC. Within a linearly forced harmonic oscillator model of vibrational excitation, we show how the vibrational amplitude is related to the pulse envelope, and independent of the carrier frequency of the laser pulse, in the DSC regime. Furthermore, we shed light on the DSC regarding the construction of optimal pulse envelopes - from a time-domain as well as a frequency-domain perspective. Finally, in a numerical study beyond the linearly forced harmonic oscillator model, we show that a pulse envelope can be constructed such that a vibrational excitation into a specific excited vibrational eigenstate is accomplished. The pulse envelope is constructed such that high intensities are avoided in order to eliminate the process of ionization. PMID- 27369514 TI - Auxiliary-field quantum Monte Carlo calculations of the molybdenum dimer. AB - Chemical accuracy is difficult to achieve for systems with transition metal atoms. Third row transition metal atoms are particularly challenging due to strong electron-electron correlation in localized d-orbitals. The Cr2 molecule is an outstanding example, which we previously treated with highly accurate auxiliary-field quantum Monte Carlo (AFQMC) calculations [W. Purwanto et al., J. Chem. Phys. 142, 064302 (2015)]. Somewhat surprisingly, computational description of the isoelectronic Mo2 dimer has also, to date, been scattered and less than satisfactory. We present high-level theoretical benchmarks of the Mo2 singlet ground state (X(1)Sigmag (+)) and first triplet excited state (a(3)Sigmau (+)), using the phaseless AFQMC calculations. Extrapolation to the complete basis set limit is performed. Excellent agreement with experimental spectroscopic constants is obtained. We also present a comparison of the correlation effects in Cr2 and Mo2. PMID- 27369516 TI - Interruption of electronically excited Xe dimer formation by the photoassociation of Xe(6s[3/2]2)-Xe(5p(6) (1)S0) thermal collision pairs. AB - The diatomic collisional intermediate responsible for the formation of an electronically excited molecule by teratomic recombination has been observed in both the spectral and temporal domains by laser spectroscopy. We report experiments demonstrating thermal Xe(6s[3/2]2)-Xe(5p(6) (1)S0) atomic collision pairs to be the immediate precursor to the formation of Xe2 (*)(a(3)Sigmau (+),A(1)Sigmau (+)) by the three body process: Xe(*)(6s) + 2Xe ? Xe2 (*) + Xe, where the asterisk denotes an excited electronic state. Photoassociating Xe(6s) Xe atomic pairs by free ? free transitions of the collision complex interrupts the production of the electronically excited Xe dimer, thereby suppressing Xe2 spontaneous emission in the vacuum ultraviolet (VUV, lambda ~ 172 nm, A(1)Sigmau (+)->X(1)Sigmag (+)). Intercepting Xe(6s)-Xe pairs before the complex is stabilized by the arrival of the third atom in the teratomic collision process selectively depletes the pair population in a specific Franck-Condon region determined by the probe laser wavelength (lambda). Measurements of the variation of VUV emission suppression with lambda provide a spectral signature of the [Xe(6s[3/2]2) - Xe((1)S0)](*) complex and map the probe laser wavelength onto the thermal energy (epsilon") of the incoming collision pairs. PMID- 27369517 TI - Electronic transitions of C5H(+) and C5H: neon matrix and CASPT2 studies. AB - Two electronic transitions at 512.3 and 250 nm of linear-C5H(+) are detected following mass-selective deposition of m/z = 61 cations into a 6 K neon matrix and assigned to the 1 (1)Pi<-X (1)Sigma(+) and 1 (1)Sigma(+)<-X (1)Sigma(+) systems. Five absorption systems of l-C5H with origin bands at 528,7, 482.6, 429.0, 368.5, and 326.8 nm are observed after neutralization of the cations in the matrix and identified as transitions from the X (2)Pi to 1 (2)Delta, 1 (2)Sigma (-), 1 (2)Sigma(+), 2 (2)Pi, and 3 (2)Pi electronic states. The assignment to specific structures is based on calculated excitation energies, vibrational frequencies in the electronic states, along with simulated Franck Condon profiles. PMID- 27369519 TI - Imaging a multidimensional multichannel potential energy surface: Photodetachment of H(-)(NH3) and NH4 (.). AB - Probes of the Born-Oppenheimer potential energy surfaces governing polyatomic molecules often rely on spectroscopy for the bound regions or collision experiments in the continuum. A combined spectroscopic and half-collision approach to image nuclear dynamics in a multidimensional and multichannel system is reported here. The Rydberg radical NH4 and the double Rydberg anion NH4 (-) represent a polyatomic system for benchmarking electronic structure and nine dimensional quantum dynamics calculations. Photodetachment of the H(-)(NH3) ion dipole complex and the NH4 (-) DRA probes different regions on the neutral NH4 PES. Photoelectron energy and angular distributions at photon energies of 1.17, 1.60, and 2.33 eV compare well with quantum dynamics. Photoelectron-photofragment coincidence experiments indicate dissociation of the nascent NH4 Rydberg radical occurs to H + NH3 with a peak kinetic energy of 0.13 eV, showing the ground state of NH4 to be unstable, decaying by tunneling-induced dissociation on a time scale beyond the present scope of multidimensional quantum dynamics. PMID- 27369518 TI - NEXAFS spectroscopy and site-specific fragmentation of N-methylformamide, N,N dimethylformamide, and N,N-dimethylacetamide. AB - Near-edge X-ray absorption fine-structure (NEXAFS) spectra measured at the C, N, and O K-edges for three molecules containing the amide moiety, N-methylformamide (HCONHCH3), N,N-dimethylformamide (HCON(CH3)2), and N,N-dimethylacetamide (CH3CON(CH3)2) are presented. These molecules have similar structures and differ by the number of methyl groups located at the molecular ends. The fragmentation of these molecules after resonant excitation at different K-edge resonances is also investigated, using a 3D-ion imaging time-of-flight spectrometer. A comparison between the molecules with respect to the relative contributions of the fragments created upon excitation at distinct resonances reveals site specific fragmentation. Further information about the character of the core excitation and dissociation process is obtained from the angular distributions of the ion fragments. PMID- 27369520 TI - Evidence for concerted ring opening and C-Br bond breaking in UV-excited bromocyclopropane. AB - Photodissociation of gaseous bromocyclopropane via its A-band continuum has been studied at excitation wavelengths ranging from 230 nm to 267 nm. Velocity-map images of ground-state bromine atoms (Br), spin-orbit excited bromine atoms (Br(*)), and C3H5 hydrocarbon radicals reveal the kinetic energies of these various photofragments. Both Br and Br(*) atoms are predominantly generated via repulsive excited electronic states in a prompt photodissociation process in which the hydrocarbon co-fragment is a cyclopropyl radical. However, the images obtained at the mass of the hydrocarbon radical fragment identify a channel with total kinetic energy greater than that deduced from the Br and Br(*) images, and with a kinetic energy distribution that exceeds the energetic limit for Br + cyclopropyl radical products. The velocity-map images of these C3H5 fragments have lower angular anisotropies than measured for Br and Br(*), indicating molecular restructuring during dissociation. The high kinetic energy C3H5 signals are assigned to allyl radicals generated by a minor photochemical pathway which involves concerted C-Br bond dissociation and cyclopropyl ring-opening following single ultraviolet (UV)-photon absorption. Slow photofragments also contribute to the velocity map images obtained at the C3H5 radical mass, but the corresponding slow Br atoms are not observed. These features in the images are attributed to C3H5 (+) from the photodissociation of the C3H5Br(+) molecular cation following two-photon ionization of the parent compound. This assignment is confirmed by 118 nm vacuum ultraviolet ionization studies that prepare the molecular cation in its ground electronic state prior to UV photodissociation. PMID- 27369521 TI - Application of classical thermodynamics to the conductivity in non-polar media. AB - Electrical conductivity in non-polar media is a subject which recently regained interest. If most of experiments and theoretical developments were done more than 50 years ago, new experiments and theories have been recently published. As the electrical conductivity describes, at low field, the equilibrium state of a system, it is natural to apply theories based on equilibrium thermodynamics. In this article, well-established classical thermodynamics and solvations models are applied to recently published data. This enables to get a new insight in intriguing phenomena, such as the linear dependence of the conductivity on the concentration of ionic surfactant and the evaluation of conductivity for the mixture of two miscible fluids, such as alcohol and alcane, which have very different conductivities. PMID- 27369522 TI - Transport properties and Stokes-Einstein relation in Al-rich liquid alloys. AB - We use ab initio molecular dynamics simulations to study the transport properties and the validity of the Stokes-Einstein relation in Al-rich liquid alloys with Ni, Cu, and Zn as alloying elements. First, we show that the composition and temperature dependence of their transport properties present different behaviors, which can be related to their local structural ordering. Then, we evidence that the competition between the local icosahedral ordering and the local chemical ordering may cause the breakdown of the Stokes-Einstein relation even in the liquid phase. We demonstrate that this breakdown can be captured by entropy scaling relationships developed by Rosenfeld and using the two-body excess entropy. Our findings provide a unique framework to study the relation between structure, thermodynamics, and dynamics in metallic melts and pave the way towards the explanation of various complex transport properties in metallic melts. PMID- 27369523 TI - Glass transition and stable glass formation of tetrachloromethane. AB - Physical vapor deposition (PVD) has been used to prepare organic glasses with very high kinetic stability and it has been suggested that molecular anisotropy is a prerequisite for stable glass formation. Here we use PVD to prepare glasses of tetrachloromethane, a simple organic molecule with a nearly isotropic molecular structure. In situ AC nanocalorimetry was used to characterize the vapor-deposited glasses. Glasses of high kinetic stability were produced by deposition near 0.8 Tg. The isothermal transformation of the vapor-deposited glasses into the supercooled liquid state gave further evidence that tetrachloromethane forms glasses with high kinetic stability, with the transformation time exceeding the structural relaxation time of the supercooled liquid by a factor of 10(3). The glass transition temperature of liquid-cooled tetrachloromethane is determined as Tg ~ 78 K, which is different from previously reported values. The frequency dependence of the glass transition was also determined and the fragility was estimated as m ~ 118. The successful formation of PVD glasses of tetrachloromethane which have high kinetic stability argues that molecular asymmetry is not a prerequisite for stable glass formation. PMID- 27369524 TI - Analyzing aging under oscillatory strain field through the soft glassy rheology model. AB - In this work, we solve the Soft Glassy Rheology (SGR) model under application of oscillatory deformation field with varying magnitudes of strain as well as frequency for different noise temperatures. In the glassy domain, the SGR model undergoes time evolution of elastic modulus. Increase in strain magnitude beyond the linear regime is observed to enhance the rate of aging as manifested by a faster evolution of elastic modulus with increase in strain amplitude due to overaging. However at higher strain magnitudes, the rejuvenation effect starts dominating over the aging, thereby reducing the rate at which elastic modulus evolves. We also plot the aging phase diagram describing an occurrence of the linear, the overaging, and the rejuvenation regimes as a function of strain and frequency for different noise temperatures. The aging phase diagram suggests that while the linear regime remains unaffected by the changes in frequency and noise temperature, the width of the overaging regime increases with increase in frequency and noise temperature. We also study the time evolution of the shapes of relaxation time spectra as a function of strain amplitude, which renders further insight into the overaging and the rejuvenation behavior. While the phenomenon of overaging is observed to be an inherent character of the SGR model, experimentally not all the materials demonstrate overaging. Such a discrepancy suggests that the energy well depths before and after a yielding event may not be completely uncorrelated as assumed in the SGR formalism. PMID- 27369525 TI - Comparative study of the Gruneisen parameter for 28 pure fluids. AB - The Gruneisen parameter gammaG is widely used for studying thermal properties of solids at high pressure and also has received increasing interest in different applications of non-ideal fluid dynamics. Because there is a lack of systematic studies of the Gruneisen parameter in the entire fluid region, this study aims to fill this gap. Gruneisen parameter data from molecular modelling and simulation are reported for 28 pure fluids and are compared with results calculated from fundamental equations of state that are based on extensive experimental data sets. We show that the Gruneisen parameter follows a general density-temperature trend and characterize the fluid systems by specifying a span of minimum and maximum values of gammaG. Exceptions to this trend can be found for water. PMID- 27369526 TI - The melting of stable glasses is governed by nucleation-and-growth dynamics. AB - We discuss the microscopic mechanisms by which low-temperature amorphous states, such as ultrastable glasses, transform into equilibrium fluids, after a sudden temperature increase. Experiments suggest that this process is similar to the melting of crystals, thus differing from the behaviour found in ordinary glasses. We rationalize these observations using the physical idea that the transformation process takes place close to a "hidden" equilibrium first-order phase transition, which is observed in systems of coupled replicas. We illustrate our views using simulation results for a simple two-dimensional plaquette spin model, which is known to exhibit a range of glassy behaviour. Our results suggest that nucleation and-growth dynamics, as found near ordinary first-order transitions, is also the correct theoretical framework to analyse the melting of ultrastable glasses. Our approach provides a unified understanding of multiple experimental observations, such as propagating melting fronts, large kinetic stability ratios, and "giant" dynamic length scales. We also provide a comprehensive discussion of available theoretical pictures proposed in the context of ultrastable glass melting. PMID- 27369527 TI - Phase diagram of ammonium perchlorate: Raman spectroscopic constrains at high pressures and temperatures. AB - We present the pressure-temperature (PT) induced physical and chemical transformations in ammonium perchlorates (APs) up to 50 GPa and 450 degrees C, using diamond anvil cells and confocal micro-Raman spectroscopy, which provide new constraints for the phase diagram of AP. The results show spectral evidences for three new polymorphs (III, IV, and VI) of AP, in addition to two previously known phases (I and II), at various PT conditions with varying degrees of hydrogen bonding and lack of strong spectral evidence for previously known high temperature cubic phase (phase V). Upon further heating, AP chemically decomposes to N2, N2O, and H2O. The present phase diagram is, therefore, in sharp contrast to the previous one, underscoring a rich polymorphism, a large stability field for solids, and a replacement of the melt with a decomposition line. PMID- 27369528 TI - Condensation on nanorods by molecular dynamics. AB - Many recent experimental studies have been conducted on constructing nanorods and nanowires to use in a wide range of applications. In this study, molecular dynamics is used to directly examine the condensation rate of nanorods and the results are compared with other basic configurations such as cubes or spheres. According to previous studies conducted by Suh and Yasuoka [J. Phys. Chem. B 115, 10631 (2011); 116, 14637 (2012)], a simple change in the configuration of the seed produces a shape effect, where the curvature of the solid seed surface directly affects the growth generating an orderly difference depending on the curvature. Nanoscale cuboids or nanorods were studied to find an aspect ratio effect when condensation occurs on the surface. Various aspect ratios were examined for different nanorod sizes over a wide range of supersaturation ratios. The results show that the growth rate of the nanorod is independent of the supersaturation ratio, which was also observed for the sphere and cube. The growth rate for the rod fell between those of the cube and the sphere, and this is due to an increase in the surface area of the nanorod compared to the cube and curvature effect in comparison with the sphere. A clear size dependence of the seed was observed, which is also similar to the cube and sphere. Furthermore, no aspect ratio influence was seen for the growth rate. This does not mean that the actual amount of condensation is the same for longer seeds, but rather from the definition of the growth rate, the amount of accumulation per unit area is the same for all seed lengths. PMID- 27369529 TI - Adsorbed states of chlorophenol on Cu(110) and controlled switching of single molecule junctions. AB - A molecular junction of substituted benzene (chlorophenol) is fabricated and controlled by using a scanning tunneling microscope (STM). Prior to the junction formation, the bonding geometry of the molecule on the surface is characterized by STM and electron energy loss spectroscopy (EELS). EELS shows that the OH group of chlorophenol is dissociated on Cu(110) and that the molecule is bonded nearly flat to the surface via an O atom, with the Cl group intact. We demonstrate controlled contact of an STM tip to the "available" Cl group and lift-up of the molecule while it is anchored to the surface via an O atom. The asymmetric bonding motifs of the molecule to the electrodes allow for reversible control of the junction. PMID- 27369530 TI - Random sequential adsorption on imprecise lattice. AB - We report a surprising result, established by numerical simulations and analytical arguments for a one-dimensional lattice model of random sequential adsorption, that even an arbitrarily small imprecision in the lattice-site localization changes the convergence to jamming from fast, exponential, to slow, power-law, with, for some parameter values, a discontinuous jump in the jamming coverage value. This finding has implications for irreversible deposition on patterned substrates with pre-made landing sites for particle attachment. We also consider a general problem of the particle (depositing object) size not an exact multiple of the lattice spacing, and the lattice sites themselves imprecise, broadened into allowed-deposition intervals. Regions of exponential vs. power-law convergence to jamming are identified, and certain conclusions regarding the jamming coverage are argued for analytically and confirmed numerically. PMID- 27369531 TI - A DFT investigation of the adsorption of iodine compounds and water in H-, Na-, Ag-, and Cu- mordenite. AB - The potential use of some cation-exchanged mordenite (H(+), Na(+), Cu(+), and Ag(+)) as a selective adsorbent for volatile iodine species (ICH3 and I2), which can be released during a nuclear accident together with a steam carrier gas, is investigated using density functional theory. It is found that in the case of Cu MOR and Ag-MOR, the absolute values of interaction energies of ICH3 and I2 are higher than that of water which indicates that these forms of zeolite could be suitable for selective adsorption of iodine species. In contrast, the H-MOR and Na-MOR are found to be unsuitable for this purpose. A systematic investigation of all adsorption sites allowed us to analyze the structural effects affecting the adsorption behavior. For the Ag-MOR and Cu-MOR zeolites, the iodine compounds are adsorbed preferentially in the large channel of mordenite (main channel) while water prefers the small channel or the side pocket where it forms stronger hydrogen bonds. The factors governing the interaction energies between the cationic sites and the different molecules are analyzed and the important role of van der Waals interactions in these systems is highlighted. PMID- 27369532 TI - Coverage-dependent adsorption and desorption of oxygen on Pd(100). AB - We have studied the adsorption and desorption of O2 on Pd(100) by supersonic molecular beam techniques and thermal desorption spectroscopy. Adsorption measurements on the bare surface confirm that O2 initially dissociates for all kinetic energies between 56 and 380 meV and surface temperatures between 100 and 600 K via a direct mechanism. At and below 150 K, continued adsorption leads to a combined O/O2 overlayer. Dissociation of molecularly bound O2 during a subsequent temperature ramp leads to unexpected high atomic oxygen coverages, which are also obtained at high incident energy and high surface temperature. At intermediate temperatures and energies, these high final coverages are not obtained. Our results show that kinetic energy of the gas phase reactant and reaction energy dissipated during O2 dissociation on the cold surface both enable activated nucleation of high-coverage surface structures. We suggest that excitation of local substrate phonons may play a crucial role in oxygen dissociation at any coverage. PMID- 27369533 TI - Post-Hartree-Fock studies of the He/Mg(0001) interaction: Anti-corrugation, screening, and pairwise additivity. AB - The adsorption of noble gases on metallic surfaces represents a paradigmatic case of van-der-Waals (vdW) interaction due to the role of screening effects on the corrugation of the interaction potential [J. L. F. Da Silva et al., Phys. Rev. Lett. 90, 066104 (2003)]. The extremely small adsorption energy of He atoms on the Mg(0001) surface (below 3 meV) and the delocalized nature and mobility of the surface electrons make the He/Mg(0001) system particularly challenging, even for state-of-the-art vdW-corrected density functional-based (vdW-DFT) approaches [M. P. de Lara-Castells et al., J. Chem. Phys. 143, 194701 (2015)]. In this work, we meet this challenge by applying two different procedures. First, the dispersion corrected second-order Moller-Plesset perturbation theory (MP2C) approach is adopted, using bare metal clusters of increasing size. Second, the method of increments [H. Stoll, J. Chem. Phys. 97, 8449 (1992)] is applied at coupled cluster singles and doubles and perturbative triples level, using embedded cluster models of the metal surface. Both approaches provide clear evidences of the anti-corrugation of the interaction potential: the He atom prefers on-top sites, instead of the expected hollow sites. This is interpreted as a signature of the screening of the He atom by the metal for the on-top configuration. The strong screening in the metal is clearly reflected in the relative contribution of successively deeper surface layers to the main dispersion contribution. Aimed to assist future dynamical simulations, a pairwise potential model for the He/surface interaction as a sum of effective He-Mg pair potentials is also presented, as an improvement of the approximation using isolated He-Mg pairs. PMID- 27369535 TI - AFM investigation of effect of absorbed water layer structure on growth mechanism of octadecyltrichlorosilane self-assembled monolayer on oxidized silicon. AB - The growth mechanism of an octadecyltrichlorosilane (OTS) self-assembled monolayer on a silicon oxide surface at various relative humidities has been investigated. Atomic force microscopy images show that excess water may actually hinder the nucleation and growth of OTS islands. A moderate amount of water is favorable for the nucleation and growth of OTS islands in the initial stage; however, the completion of the monolayer is very slow in the final stage. The growth of OTS islands on a low-water-content surface maintains a relatively constant speed and requires the least amount of time. The mobility of water molecules is thought to play an important role in the OTS monolayers, and a low mobility water layer provides a steady condition for OTS monolayer growth. PMID- 27369534 TI - Modeling surface motion effects in N2 dissociation on W(110): Ab initio molecular dynamics calculations and generalized Langevin oscillator model. AB - Accurately modeling surface temperature and surface motion effects is necessary to study molecule-surface reactions in which the energy dissipation to surface phonons can largely affect the observables of interest. We present here a critical comparison of two methods that allow to model such effects, namely, the ab initio molecular dynamics (AIMD) method and the generalized Langevin oscillator (GLO) model, using the dissociation of N2 on W(110) as a benchmark. AIMD is highly accurate as the surface atoms are explicitly part of the dynamics, but this advantage comes with a large computational cost. The GLO model is much more computationally convenient, but accounts for lattice motion effects in a very approximate way. Results show that, despite its simplicity, the GLO model is able to capture the physics of the system to a large extent, returning dissociation probabilities which are in better agreement with AIMD than static surface results. Furthermore, the GLO model and the AIMD method predict very similar energy transfer to the lattice degrees of freedom in the non-reactive events, and similar dissociation dynamics. PMID- 27369536 TI - Striped gold nanoparticles: New insights from molecular dynamics simulations. AB - Recent simulations have improved our knowledge of the molecular-level structure and hydration properties of mixed self-assembled monolayers (SAMs) with equal and unequal alkyl thiols at three different arrangements, namely, random, patchy, and Janus. In our previous work [V. Vasumathi et al., J. Phys. Chem. C 119, 3199-3209 (2015)], we showed that the bending of longer thiols over shorter ones clearly depends on the thiols' arrangements and chemical nature of their terminal groups. In addition, such a thiol bending revealed to have a strong impact on the structural and hydration properties of SAMs coated on gold nanoparticles (AuNPs). In this paper, we extend our previous atomistic simulation study to investigate the bending of longer thiols by increasing the stripe thickness of mixed SAMs of equal and unequal lengths coated on AuNPs. We study also the effect of stripe thickness on the structural morphology and hydration of the coated SAMs. Our results show that the structural and hydration properties of SAMs are affected by the stripe thickness for mixtures of alkyl thiols with unequal chain length but not for equal length. Hence, the stability of the stripe configuration depends on the alkyl's chain length, the length difference between the thiol mixtures, and solvent properties. PMID- 27369537 TI - Phase reference in phase-sensitive sum-frequency vibrational spectroscopy. AB - Phase-sensitive sum-frequency vibrational spectroscopy (PS-SFVS) has been established as a powerful technique for surface characterization, but for it to generate a reliable spectrum, accurate phase measurement with a well-defined phase reference is most important. Incorrect phase measurement can lead to significant distortion of a spectrum, as recently seen in the case for the air/water interface. In this work, we show theoretically and experimentally that a transparent, highly nonlinear crystal, such as quartz and barium borate, can be a good phase reference if the surface is clean and unstrained and the crystal is properly oriented to yield a strong SF output. In such cases, the reflected SF signal is dominated by the bulk electric dipole contribution and its phase is either +90 degrees or -90 degrees . On the other hand, materials with inversion symmetry, such as water, fused quartz, and CaF2 are not good phase references due to the quadrupole contribution and phase dispersion at the interface. Using a proper phase reference in PS-SFVS, we have found the most reliable OH stretching spectrum for the air/water interface. The positive band at low frequencies in the imaginary component of the spectrum, which has garnered much interest and been interpreted by many to be due to strongly hydrogen-bonded water species, is no longer present. A weak positive feature however still exists. Its magnitude approximately equals to that of air/D2O away from resonances, suggesting that this positive feature is unrelated to surface resonance of water. PMID- 27369538 TI - Effective interactions between nanoparticles: Creating temperature-independent solvation environments for self-assembly. AB - The extent to which solvent-mediated effective interactions between nanoparticles can be predicted based on structure and associated thermodynamic estimators for bulk solvents and for solvation of single and pairs of nanoparticles is studied here. As a test of the approach, we analyse the strategy for creating temperature independent solvent environments using a series of homologous chain fluids as solvents, as suggested by an experimental paper [M. I. Bodnarchuk et al., J. Am. Chem. Soc. 132, 11967 (2010)]. Our conclusions are based on molecular dynamics simulations of Au140(SC10H21)62 nanoparticles in n-alkane solvents, specifically hexane, octane, decane and dodecane, using the TraPPE-UA potential to model the alkanes and alkylthiols. The 140-atom gold core of the nanocrystal is held rigid in a truncated octahedral geometry and the gold-thiolate interaction is modeled using a Morse potential. The experimental observation was that the structural and rheological properties of n-alkane solvents are constant over a temperature range determined by equivalent solvent vapour pressures. We show that this is a consequence of the fact that long chain alkane liquids behave to a good approximation as simple liquids formed by packing of monomeric methyl/methylene units. Over the corresponding temperature range (233-361 K), the solvation environment is approximately constant at the single and pair nanoparticle levels under good solvent conditions. However, quantitative variations of the order of 10%-20% do exist in various quantities, such as molar volume of solute at infinite dilution, entropy of solvation, and onset distance for soft repulsions. In the opposite limit of a poor solvent, represented by vacuum in this study, the effective interactions between nanoparticles are no longer temperature independent with attractive interactions increasing by up to 50% on decreasing the temperature from 361 K to 290 K, accompanied by an increase in emergent anisotropy due to correlation of mass dipoles on the two nanoparticles. One expects therefore that during self-assembly using solvent evaporation, temperature can be used as a structure-directing factor as long as good solvent conditions are maintained. It also suggests that disordered configurations may emerge as solvent quality decreases due to increasing role of short-range attractions and ligand fluctuation-driven anisotropy. The possibilities of using structural estimators of various thermodynamic quantities to analyse the interplay of ligand fluctuations and solvent quality in self-assembly as well as to design solvation environments are discussed. PMID- 27369539 TI - Thermal gravitational separation of ternary mixture n dodecane/isobutylbenzene/tetralin components in a porous medium. AB - Our present work focuses on the coupling between thermal diffusion and convection in order to improve the thermal gravitational separation of mixture components. The separation phenomenon was studied in a porous medium contained in vertical columns. We performed analytical and numerical simulations to corroborate the experimental measurements of the thermal diffusion coefficients of ternary mixture n-dodecane, isobutylbenzene, and tetralin obtained in microgravity in the international space station. Our approach corroborates the existing data published in the literature. The authors show that it is possible to quantify and to optimize the species separation for ternary mixtures. The authors checked, for ternary mixtures, the validity of the "forgotten effect hypothesis" established for binary mixtures by Furry, Jones, and Onsager. Two complete and different analytical resolution methods were used in order to describe the separation in terms of Lewis numbers, the separation ratios, the cross-diffusion coefficients, and the Rayleigh number. The analytical model is based on the parallel flow approximation. In order to validate this model, a numerical simulation was performed using the finite element method. From our new approach to vertical separation columns, new relations for mass fraction gradients and the optimal Rayleigh number for each component of the ternary mixture were obtained. PMID- 27369540 TI - Diagram of states and morphologies of flexible-semiflexible copolymer chains: A Monte Carlo simulation. AB - A single copolymer chain consisting of multiple flexible (F) and semiflexible (S) blocks has been studied using a continuum bead-spring model by Stochastic Approximation Monte Carlo simulations, which determine the density of states of the model. The only difference between F and S blocks is the intramolecular bending potential, all non-bonded interactions are equal. The state diagrams for this class of models display multiple nematic phases in the collapsed state, characterized through a demixing of the blocks of different stiffness and orientational ordering of the stiff blocks. We observe dumbbell-like morphologies, lamellar phases, and for the larger block lengths also Saturn-like structures with a core of flexible segments and the stiff segments forming a ring around the core. PMID- 27369541 TI - Bond breaking in epoxy systems: A combined QM/MM approach. AB - A novel method to combine quantum mechanics (QM) and molecular mechanics has been developed to accurately and efficiently account for covalent bond breaking in polymer systems under high strain without the use of predetermined break locations. Use of this method will provide a better fundamental understanding of the mechano-chemical origins of fracture in thermosets. Since classical force fields cannot accurately account for bond breaking, and QM is too demanding to simulate large systems, a hybrid approach is required. In the method presented here, strain is applied to the system using a classical force field, and all bond lengths are monitored. When a bond is stretched past a threshold value, a zone surrounding the bond is used in a QM energy minimization to determine which, if any, bonds break. The QM results are then used to reconstitute the system to continue the classical simulation at progressively larger strain until another QM calculation is triggered. In this way, a QM calculation is only computed when and where needed, allowing for efficient simulations. A robust QM method for energy minimization has been determined, as well as appropriate values for the QM zone size and the threshold bond length. Compute times do not differ dramatically from classical molecular mechanical simulations. PMID- 27369542 TI - Effect of functionality on unentangled star polymers at equilibrium and under shear flow. AB - The properties of unentangled star polymers with arm length Nf = 20 beads and functionality f (3 <= f <= 60) are investigated at equilibrium and under shear flow by coarse-grained molecular dynamics simulations. At equilibrium, the star polymer shows a crossover from a linear, freely penetrable, extremely soft object to a spherical, slightly hard object with an impenetrable center with increasing f. The results confirm that the arm relaxation is essentially independent of f and stars of large f form a liquid-like structure. In shear flow, the polymer deformation and alignment are calculated as well as the shear-induced rotational dynamics as function of shear rate. These properties are found to exhibit qualitative changes at an f-independent shear rate, gammap, which is a consequence of competition between chain relaxation and imposed flow. Shear thinning is characterized by shear viscosity and normal stress differences. With increasing f, the critical shear rate for the onset of shear thinning decreases from gammap for f = 3 to a smaller value. Our results also show that shear thinning of stars of large f arise from the collapse of liquid-like structures at low shear rates (gamma?gammap), where chains have no deformation; at high shear rates (gamma?gammap), shear thinning is mainly attributed to the chain stretching and orientation as linear polymers. PMID- 27369543 TI - Long-range energy transport in photosystem II. AB - We simulate the long-range inter-complex electronic energy transfer in photosystem II-from the antenna complex, via a core complex, to the reaction center-using a non-Markovian (ZOFE) quantum master equation description that allows the electronic coherence involved in the energy transfer to be explicitly included at all length scales. This allows us to identify all locations where coherence is manifested and to further identify the pathways of the energy transfer in the full network of coupled chromophores using a description based on excitation probability currents. We investigate how the energy transfer depends on the initial excitation-localized, coherent initial excitation versus delocalized, incoherent initial excitation-and find that the overall energy transfer is remarkably robust with respect to such strong variations of the initial condition. To explore the importance of vibrationally enhanced transfer and to address the question of optimization in the system parameters, we systematically vary the strength of the coupling between the electronic and the vibrational degrees of freedom. We find that the natural parameters lie in a (broad) region that enables optimal transfer efficiency and that the overall long range energy transfer on a ns time scale appears to be very robust with respect to variations in the vibronic coupling of up to an order of magnitude. Nevertheless, vibrationally enhanced transfer appears to be crucial to obtain a high transfer efficiency, with the latter falling sharply for couplings outside the optimal range. Comparison of our full quantum simulations to results obtained with a "classical" rate equation based on a modified-Redfield/generalized-Forster description previously used to simulate energy transfer dynamics in the entire photosystem II complex shows good agreement for the overall time scales of excitation energy transport. PMID- 27369544 TI - On the properties of a bundle of flexible actin filaments in an optical trap. AB - We establish the statistical mechanics framework for a bundle of Nf living and uncrosslinked actin filaments in a supercritical solution of free monomers pressing against a mobile wall. The filaments are anchored normally to a fixed planar surface at one of their ends and, because of their limited flexibility, they grow almost parallel to each other. Their growing ends hit a moving obstacle, depicted as a second planar wall, parallel to the previous one and subjected to a harmonic compressive force. The force constant is denoted as the trap strength while the distance between the two walls as the trap length to make contact with the experimental optical trap apparatus. For an ideal solution of reactive filaments and free monomers at fixed free monomer chemical potential MU1, we obtain the general expression for the grand potential from which we derive averages and distributions of relevant physical quantities, namely, the obstacle position, the bundle polymerization force, and the number of filaments in direct contact with the wall. The grafted living filaments are modeled as discrete Wormlike chains, with F-actin persistence length lp, subject to discrete contour length variations +/-d (the monomer size) to model single monomer (de)polymerization steps. Rigid filaments (lp = infinity), either isolated or in bundles, all provide average values of the stalling force in agreement with Hill's predictions Fs (H)=NfkBTln(rho1/rho1c)/d, independent of the average trap length. Here rho1 is the density of free monomers in the solution and rho1c its critical value at which the filament does not grow nor shrink in the absence of external forces. Flexible filaments (lp < infinity) instead, for values of the trap strength suitable to prevent their lateral escape, provide an average bundle force and an average trap length slightly larger than the corresponding rigid cases (few percents). Still the stalling force remains nearly independent on the average trap length, but results from the product of two strongly L-dependent contributions: the fraction of touching filaments ?(O.T.) (2) and the single filament buckling force ?(O.T.) (-2). PMID- 27369545 TI - Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study. AB - The time-resolved parallel artificial membrane permeability assay with fluorescence detection and comprehensive computer simulations are used to study the passive permeation of three aromatic dipeptides-N-acetyl-phenylalanineamide (NAFA), N-acetyltyrosineamide (NAYA), and N-acetyl-tryptophanamide (NATA) through a 1,2-dioleoyl-sn-glycero-3-phospocholine (DOPC) lipid bilayer. Measured permeation times and permeability coefficients show fastest translocation for NAFA, slowest for NAYA, and intermediate for NATA under physiological temperature and pH. Computationally, we perform umbrella sampling simulations to model the structure, dynamics, and interactions of the peptides as a function of z, the distance from lipid bilayer. The calculated profiles of the potential of mean force show two strong effects-preferential binding of each of the three peptides to the lipid interface and large free energy barriers in the membrane center. We use several approaches to calculate the position-dependent translational diffusion coefficients D(z), including one based on numerical solution the Smoluchowski equation. Surprisingly, computed D(z) values change very little with reaction coordinate and are also quite similar for the three peptides studied. In contrast, calculated values of sidechain rotational correlation times taurot(z) show extremely large changes with peptide membrane insertion-values become 100 times larger in the headgroup region and 10 times larger at interface and in membrane center, relative to solution. The peptides' conformational freedom becomes systematically more restricted as they enter the membrane, sampling alpha and beta and C7eq basins in solution, alpha and C7eq at the interface, and C7eq only in the center. Residual waters of solvation remain around the peptides even in the membrane center. Overall, our study provides an improved microscopic understanding of passive peptide permeation through membranes, especially on the sensitivity of rotational diffusion to position relative to the bilayer. PMID- 27369546 TI - Fate of Hancock valve in tricuspid position 36 years after implantation. AB - Mid- to long-term durability of bioprosthesis in tricuspid position is acceptable. However, little is known about more extended long-term structural valve changes of Hancock valve. In present report, we describe Hancock valve images 36 years after implantation. PMID- 27369548 TI - [Erratum to: Ischemic stroke after intracranial occlusion of a major intracranial artery : Interventional radiological treatment versus i. v. thrombolysis therapy alone]. PMID- 27369547 TI - Multiscale Analysis of Neurite Orientation and Spatial Organization in Neuronal Images. AB - The spatial organization of neurites, the thin processes (i.e., dendrites and axons) that stem from a neuron's soma, conveys structural information required for proper brain function. The alignment, direction and overall geometry of neurites in the brain are subject to continuous remodeling in response to healthy and noxious stimuli. In the developing brain, during neurogenesis or in neuroregeneration, these structural changes are indicators of the ability of neurons to establish axon-to-dendrite connections that can ultimately develop into functional synapses. Enabling a proper quantification of this structural remodeling would facilitate the identification of new phenotypic criteria to classify developmental stages and further our understanding of brain function. However, adequate algorithms to accurately and reliably quantify neurite orientation and alignment are still lacking. To fill this gap, we introduce a novel algorithm that relies on multiscale directional filters designed to measure local neurites orientation over multiple scales. This innovative approach allows us to discriminate the physical orientation of neurites from finer scale phenomena associated with local irregularities and noise. Building on this multiscale framework, we also introduce a notion of alignment score that we apply to quantify the degree of spatial organization of neurites in tissue and cultured neurons. Numerical codes were implemented in Python and released open source and freely available to the scientific community. PMID- 27369549 TI - [Imaging signs in chest diagnostics]. AB - Signs in chest imaging are defined as typical findings which can be easily recognized on x-ray photographs or computed tomography (CT) scans of the chest. They are caused by different typical pathophysiological processes. Due to the association of a certain pathophysiological cause with a given sign, knowledge and use of these signs can allow the possible differential diagnoses to be narrowed down. If other imaging findings and clinical data are additionally taken into account, the diagnosis can be made with a high degree of confidence in many cases. PMID- 27369552 TI - [Not Available]. PMID- 27369550 TI - High-throughput fluorescence screening assay for the identification and comparison of antimicrobial peptides' activity on various yeast species. AB - New antifungal compounds that circumvent the resistance of the pathogen by directly damaging yeast cell surface structures are promising agents for the treatment of fungal infections, due to their different mechanism of action from current clinically used antifungal drugs. We present here a rapid and cost effective fluorescence method suitable for identifying new potent drugs that directly target yeast cell surface structures, causing cell permeabilization and thus bypassing the multidrug resistance mechanisms of pathogens. The fluorescence assay enabled us to detect with high sensitivity damage to the Candida plasma membrane (its hyperpolarization and permeabilization) as a result of short-term exposure to the antifungal compounds. Results can be obtained in 1-2h with minimal effort and consumption of the tested compounds, also 96 samples can be analysed simultaneously. We used this method to study antimicrobial peptides isolated from the venom of bees and their synthetic analogs, compare the potency of the peptides and determine their minimal effective concentrations. The antimicrobial peptides were able to kill yeast cells at low concentrations within a 15-min treatment, the LL-III peptide exhibited a broad spectrum of antifungal activity on various Saccharomyces, pathogenic Candida and osmotolerant yeast species. PMID- 27369551 TI - Delta9-Tetrahydrocannabinolic acid synthase: The application of a plant secondary metabolite enzyme in biocatalytic chemical synthesis. AB - Delta(9)-Tetrahydrocannabinolic acid synthase (THCAS) from the secondary metabolism of Cannabis sativa L. catalyzes the oxidative formation of an intramolecular CC bond in cannabigerolic acid (CBGA) to synthesize Delta(9) tetrahydrocannabinolic acid (THCA), which is the direct precursor of Delta(9) tetrahydrocannabinol (Delta(9)-THC). Aiming on a biotechnological production of cannabinoids, we investigated the potential of the heterologously produced plant oxidase in a cell-free system on preparative scale. THCAS was characterized in an aqueous/organic two-liquid phase setup in order to solubilize the hydrophobic substrate and to allow in situ product removal. Compared to the single phase aqueous setup the specific activity decreased by a factor of approximately 2 pointing to a substrate limitation of CBGA in the two-liquid phase system. However, the specific activity remained stable for at least 3h illustrating the benefit of the two-liquid phase setup. In a repeated-batch setup, THCAS showed only a minor loss of specific activity in the third batch pointing to a high intrinsic stability and high solvent tolerance of the enzyme. Maximal space-time yields of 0.121gL(-1)h(-1) were reached proving the two-liquid phase concept suitable for biotechnological production of cannabinoids. PMID- 27369554 TI - [Not Available]. PMID- 27369553 TI - [Not Available]. PMID- 27369555 TI - [Not Available]. PMID- 27369556 TI - [Not Available]. PMID- 27369557 TI - [Not Available]. PMID- 27369558 TI - [Not Available]. PMID- 27369559 TI - [Not Available]. PMID- 27369560 TI - [Not Available]. PMID- 27369561 TI - [Not Available]. PMID- 27369562 TI - [Not Available]. PMID- 27369563 TI - [Not Available]. PMID- 27369564 TI - [Not Available]. PMID- 27369565 TI - [Not Available]. PMID- 27369566 TI - An innovative privacy preserving technique for incremental datasets on cloud computing. AB - Cloud computing (CC) is a magnificent service-based delivery with gigantic computer processing power and data storage across connected communications channels. It imparted overwhelming technological impetus in the internet (web) mediated IT industry, where users can easily share private data for further analysis and mining. Furthermore, user affable CC services enable to deploy sundry applications economically. Meanwhile, simple data sharing impelled various phishing attacks and malware assisted security threats. Some privacy sensitive applications like health services on cloud that are built with several economic and operational benefits necessitate enhanced security. Thus, absolute cyberspace security and mitigation against phishing blitz became mandatory to protect overall data privacy. Typically, diverse applications datasets are anonymized with better privacy to owners without providing all secrecy requirements to the newly added records. Some proposed techniques emphasized this issue by re anonymizing the datasets from the scratch. The utmost privacy protection over incremental datasets on CC is far from being achieved. Certainly, the distribution of huge datasets volume across multiple storage nodes limits the privacy preservation. In this view, we propose a new anonymization technique to attain better privacy protection with high data utility over distributed and incremental datasets on CC. The proficiency of data privacy preservation and improved confidentiality requirements is demonstrated through performance evaluation. PMID- 27369567 TI - OntoADR a semantic resource describing adverse drug reactions to support searching, coding, and information retrieval. AB - INTRODUCTION: Efficient searching and coding in databases that use terminological resources requires that they support efficient data retrieval. The Medical Dictionary for Regulatory Activities (MedDRA) is a reference terminology for several countries and organizations to code adverse drug reactions (ADRs) for pharmacovigilance. Ontologies that are available in the medical domain provide several advantages such as reasoning to improve data retrieval. The field of pharmacovigilance does not yet benefit from a fully operational ontology to formally represent the MedDRA terms. Our objective was to build a semantic resource based on formal description logic to improve MedDRA term retrieval and aid the generation of on-demand custom groupings by appropriately and efficiently selecting terms: OntoADR. METHODS: The method consists of the following steps: (1) mapping between MedDRA terms and SNOMED-CT, (2) generation of semantic definitions using semi-automatic methods, (3) storage of the resource and (4) manual curation by pharmacovigilance experts. RESULTS: We built a semantic resource for ADRs enabling a new type of semantics-based term search. OntoADR adds new search capabilities relative to previous approaches, overcoming the usual limitations of computation using lightweight description logic, such as the intractability of unions or negation queries, bringing it closer to user needs. Our automated approach for defining MedDRA terms enabled the association of at least one defining relationship with 67% of preferred terms. The curation work performed on our sample showed an error level of 14% for this automated approach. We tested OntoADR in practice, which allowed us to build custom groupings for several medical topics of interest. DISCUSSION: The methods we describe in this article could be adapted and extended to other terminologies which do not benefit from a formal semantic representation, thus enabling better data retrieval performance. Our custom groupings of MedDRA terms were used while performing signal detection, which suggests that the graphical user interface we are currently implementing to process OntoADR could be usefully integrated into specialized pharmacovigilance software that rely on MedDRA. PMID- 27369568 TI - Evaluation of different methods for the experimental infection of the land snail Helix aspersa with Aelurostrongylus abstrusus lungworm. AB - The laboratory maintenance of parasitic life cycles is crucial to support research in many fields of parasitology. The land snail Helix aspersa (syn. Cornu aspersum), an intermediate host of feline lungworms Aelurostrongylus abstrusus and Troglostrongylus brevior, is adopted to produce infective stages of those nematodes in laboratory condition. The aim of this study was to compare the most common methods of experimental infection of H. aspersa with first stage larvae (L1) of A. abstrusus (i.e., contact of the snail foot with the L1) with the injection of these larvae in the foot of the snail, instrumental to reduce the infection time and to maximize the output of third-stage larvae (L3). Three groups (i.e., A, B, C) of 15 H. aspersa snails were infected with L1 of A. abstrusus (n=250 for each snail), whereas a fourth group (group D) was not infected (control). Snails were individually placed for 48h on a microfilm containing L1 (group A), on a potato slice previously irrigated with a suspension of L1 (group B), or they were inoculated by injection of L1 in the posterior ventral portion of the foot (group C). Eighteen days after the infection all snails were analyzed and tissues were digested to recover L3. No difference in mortality rate was recorded among snail groups and the mean number of retrieved L3 was significantly larger in group C (71.5+/-52.9) compared to group B (38.2+/ 44.9; p=0.0161) and group A (19+/-23.3; p<0.0001). The injection of A. abstrusus L1 in the foot of H. aspersa proved to be a fast, easy to apply and effective method, resulting in the largest number of infective larvae retrieved. PMID- 27369569 TI - Efficacy of a potential DNA vaccine encoding Cryptosporidium baileyi rhomboid protein against homologous challenge in chickens. AB - The parasite Cryptosporidium baileyi can infect the larynx, trachea, bursa and cloaca of poultry, causing high mortality during severe infection and leading to substantial economic losses of the poultry industry. The rhomboid protein is very important in Cryptosporidium infection. In this study, a nucleic acid based vaccine candidate pEGFP-CbROM was constructed. After orally challenging with C. baileyi oocysts, the corresponding immune responses induced were analyzed and the immunoprotective effect evaluated in chickens. Obtained results revealed that this nucleic acid based vaccine could induce antibody responses and peripheral blood T lymphocytes proliferation significantly (P<0.05), while the peripheral blood B lymphocyte proliferation increased significantly (P<0.05) only at a high dose of 100MUg of pEGFP-CbROM, compared with the PBS control group. After C. baileyi infection, the duration of oocysts shedding was shortened by 2days in the 100MUg pEGFP-CbROM group, and the rate of reduction could reach to around 71.3%. While no significant difference in body weight gain was observed among the immunized groups (P>0.05), the differences between the immunized and the non immunized groups were found to be significant (P<0.05). Our data provides a useful basis for further work in cryptosporidiosis prevention and treatment. PMID- 27369570 TI - Laboratory and field evaluation of entomopathogenic fungi for the control of amitraz-resistant and susceptible strains of Rhipicephalus decoloratus. AB - Rhipicephalus decoloratus causes serious economic losses in cattle industry every year in East Africa. Biological control using entomopathogenic fungi is seen as a promising alternative to chemical acaricides being used for their control. The pathogenicity of Metarhizium anisopliae and of Beauveria bassiana isolates was tested in the laboratory against amitraz-resistant and amitraz-susceptible strains of R. decoloratus. Unfed larvae were sprayed with conidial suspensions of 1*10(9) conidia ml(-1). Fungal isolates were pathogenic to R. decoloratus larvae, causing mortality of between 10.0 and 100% and between 12.1 and 100% of amitraz susceptible and amitraz-resistant strains, respectively. The LT50 values of selected fungal isolates varied between 2.6-4.2days in amitraz-susceptible strain and between 2.8-3.9days in amitraz-resistant strain. The LC50 values varied between 0.4+/-0.1 and 200.0+/-60*10(3) conidia ml(-1) and between 0.1+/-0.1 and 200.0+/-31.0*10(3) conidia ml(-1) in amitraz-susceptible and amitraz-resistant strains, respectively. Metarhizium anisopliae isolate ICIPE 7 outperformed the other isolates and was selected for compatibility study with amitraz and field trial. ICIPE 7 was compatible with amitraz. In the field, four treatments including control, ICIPE 7 alone, amitraz alone and ICIPE 7/amitraz were applied on cattle. All the treatments significantly reduced the number of ticks on all the sampling dates: day 7 (F3,8=3.917; P=0.0284), day 14 (F3,8=9.090; P=0.0275), day 21 (F3,8=37.971; P=0.0001) and day 28 (F3,8=8.170; P=0.0016) compared to the control. Results of the present study indicate that ICIPE 7 can be used for the management of amitraz-resistant strain of R. decoloratus. PMID- 27369572 TI - Potential association of reduced cholinesterase activity with Trypanosoma evansi pathogenesis in buffaloes. AB - The present study aimed to investigate the association of cholinesterase activity with trypanosomosis in buffaloes. Thirty-three clinical cases of trypanosomosis in water buffaloes, found positive for trypomastigotes of T. evansi on blood smear examination, were divided into two groups based on clinical manifestations. Twenty diseased buffaloes revealing only common clinical signs were allocated to Group I, while the remaining 13 buffaloes showing common clinical manifestations along with neurological disturbances were allocated to Group II. Twelve clinically healthy buffaloes, free from any haemoprotozoa infection, were kept as healthy control (Group III). Blood samples were collected from buffaloes of all three groups to determine serum cholinesterase activity. Compared to buffaloes of healthy control group, cholinesterase activity in T. evansi-infected buffaloes of Group I and II was significantly (P<0.001) lower. However, no significant difference was observed in cholinesterase activity between the T. evansi-infected buffaloes exhibiting neurological disorders and no neurological disorders. Summing up, reduced cholinesterase activity seems to be associated with the pathogenesis of natural T. evansi infection and its clinical manifestations in buffaloes possibly by evading immune response. Further studies are warranted on association of cholinesterase activity in T. evansi-infected buffaloes with neurological disorders. PMID- 27369571 TI - Breeding for resistance to gastrointestinal nematodes - the potential in low input/output small ruminant production systems. AB - The control of gastrointestinal nematodes (GIN) is mainly based on the use of drugs, grazing management, use of copper oxide wire particles and bioactive forages. Resistance to anthelmintic drugs in small ruminants is documented worldwide. Host genetic resistance to parasites, has been increasingly used as a complementary control strategy, along with the conventional intervention methods mentioned above. Genetic diversity in resistance to GIN has been well studied in experimental and commercial flocks in temperate climates and more developed economies. However, there are very few report outputs from the more extensive low input/output smallholder systems in developing and emerging countries. Furthermore, results on quantitative trait loci (QTL) associated with nematode resistance from various studies have not always been consistent, mainly due to the different nematodes studied, different host breeds, ages, climates, natural infections versus artificial challenges, infection level at sampling periods, among others. The increasing use of genetic markers (Single Nucleotide Polymorphisms, SNPs) in GWAS or the use of whole genome sequence data and a plethora of analytic methods offer the potential to identify loci or regions associated nematode resistance. Genomic selection as a genome-wide level method overcomes the need to identify candidate genes. Benefits in genomic selection are now being realised in dairy cattle and sheep under commercial settings in the more advanced countries. However, despite the commercial benefits of using these tools, there are practical problems associated with incorporating the use of marker-assisted selection or genomic selection in low-input/output smallholder farming systems breeding schemes. Unlike anthelmintic resistance, there is no empirical evidence suggesting that nematodes will evolve rapidly in response to resistant hosts. The strategy of nematode control has evolved to a more practical manipulation of host-parasite equilibrium in grazing systems by implementation of various strategies, in which improvement of genetic resistance of small ruminant should be included. Therefore, selection for resistant hosts can be considered as one of the sustainable control strategy, although it will be most effective when used to complement other control strategies such as grazing management and improving efficiency of anthelmintics currently. PMID- 27369573 TI - Why pigs are free-roaming: Communities' perceptions, knowledge and practices regarding pig management and taeniosis/cysticercosis in a Taenia solium endemic rural area in Eastern Zambia. AB - Taenia solium cysticercosis is a neglected parasitic zoonosis in many developing countries including Zambia. Studies in Africa have shown that the underuse of sanitary facilities and the widespread occurrence of free-roaming pigs are the major risk factors for porcine cysticercosis. Socio-cultural determinants related to free range pig management and their implications for control of T. solium remain unclear. The study objective was to assess the communities' perceptions, reported practices and knowledge regarding management of pigs and taeniosis/cysticercosis (including neurocysticercosis) in an endemic rural area in Eastern Zambia, and to identify possible barriers to pig related control measures such as pig confinement. A total of 21 focus group discussions on pig husbandry practices were organized separately with men, women and children, in seven villages from Petauke district. The findings reveal that the perception of pigs and their role in society (financial, agricultural and traditional), the distribution of the management tasks among the family members owning pigs (feeding, building kraal, seeking care) and environmental aspects (feed supply, presence of bush, wood use priorities, rainy season) prevailing in the study area affect pig confinement. People have a fragmented knowledge of the pork tapeworm and its transmission. Even if negative aspects/health risks of free-range pigs keeping are perceived, people are ready to take the risk for socio-economic reasons. Finally, gender plays an important role because women, and also children, seem to have a higher perception of the risks but lack power in terms of economic decision-making compared to men. Currently pig confinement is not seen as an acceptable method to control porcine cysticercosis by many farmers in Eastern Zambia, vaccination and treatment seemed to be more appropriate. Embedded in a One Health approach, disease control programs should therefore ensure a complementary appropriate set of control strategies by engaging new sectors such as agronomy, spatial ecology and finally consider the socio-cultural context, which is likely to enhance the development of control methods that could be accepted by the communities. PMID- 27369574 TI - Combatting African Animal Trypanosomiasis (AAT) in livestock: The potential role of trypanotolerance. AB - African Animal Trypanosomiasis (AAT) is endemic in at least 37 of the 54 countries in Africa. It is estimated to cause direct and indirect losses to the livestock production industry in excess of US$ 4.5 billion per annum. A century of intervention has yielded limited success, owing largely to the extraordinary complexity of the host-parasite interaction. Trypanotolerance, which refers to the inherent ability of some African livestock breeds, notably Djallonke sheep, N'Dama cattle and West African Dwarf goats, to withstand a trypanosomiasis challenge and still remain productive without any form of therapy, is an economically sustainable option for combatting this disease. Yet trypanotolerance has not been adequately exploited in the fight against AAT. In this review, we describe new insights into the genetic basis of trypanotolerance and discuss the potential of exploring this phenomenon as an integral part of the solution for AAT, particularly, in the context of African animal production systems. PMID- 27369576 TI - Explaining variability in first grazing season heifer growth combining individually measured parasitological and clinical indicators with exposure to gastrointestinal nematode infection based on grazing management practice. AB - The objective of our study was to explain the variability of average daily weight gain (ADWG) due to gastrointestinal nematode (GIN) infection for 291 non treated first grazing season (FGS) heifers, from 12 independent groups in the western part of France, by combining parasitological and clinical indicators at individual level and grazing management indicators at group level. Parasitological indicators were faecal egg count (FEC), anti Ostertagia ostertagi antibody level (Ostertagia ODR), and pepsinogen level. Clinical indicators were diarrhea score (DISCO) and breech soiling score (BSS). At group level, grazing management practice (GMP), based on three variables (supplementation, month of turnout, grazing season duration), was clustered into three categories reflecting low, medium or high exposure (EXP) to GIN. Depending on the groups, turnout was from mid-March to early July and housing was from mid-October to late November, with a FGS duration ranging from 4 to 8.4 months. At turnout, the mean age of heifers was 8 months (range: 6-16 months) and they weighed between 175 and 268kg. In each GMP category, FEC significantly decreased between the mid-season and the housing, while Ostertagia ODR and pepsinogen level increased gradually throughout the grazing season. In contrast, clinical indicators did not show any seasonal variation. In a multivariate linear model, 22% of the ADWG variability was significantly explained by two individual indicators (Ostertagia ODR: 12.6%, DISCO: 4.8%) and by the group indicator (GMP category: 4.8%). ADWG losses due to GIN exposure (Ostertagia ODR) were estimated up to 39kg per heifer for the overall grazing season. For groups within the low EXP category the difference between animals with low (<697g/day) or high (>697g/day) ADWG was explained by the clinical indicator DISCO. In contrast, for groups within the medium and high EXP categories this difference was explained by a parasitological indicator (Ostertagia ODR). This study highlighted the value of combining both grazing management (group level) and parasitological (individual level) indicators to assess the impact of GIN on ADWG of FGS heifers. As a result, this combination might allow a better discrimination of animals or groups that may be in need of treatment in a targeting selective treatment approach. PMID- 27369575 TI - Pooling sheep faecal samples for the assessment of anthelmintic drug efficacy using McMaster and Mini-FLOTAC in gastrointestinal strongyle and Nematodirus infection. AB - In small ruminants, faecal egg counts (FECs) and reduction in FECs (FECR) are the most common methods for the assessment of intensity of gastrointestinal (GI) nematodes infections and anthelmintic drug efficacy, respectively. The main limitation of these methods is the time and cost to conduct FECs on a representative number of individual animals. A cost-saving alternative would be to examine pooled faecal samples, however little is known regarding whether pooling can give representative results. In the present study, we compared the FECR results obtained by both an individual and a pooled examination strategy across different pool sizes and analytical sensitivity of the FEC techniques. A survey was conducted on 5 sheep farms in Scotland, where anthelmintic resistance is known to be widespread. Lambs were treated with fenbendazole (4 groups), levamisole (3 groups), ivermectin (3 groups) or moxidectin (1 group). For each group, individual faecal samples were collected from 20 animals, at baseline (D0) and 14 days after (D14) anthelmintic administration. Faecal samples were analyzed as pools of 3-5, 6-10, and 14-20 individual samples. Both individual and pooled samples were screened for GI strongyle and Nematodirus eggs using two FEC techniques with three different levels of analytical sensitivity, including Mini FLOTAC (analytical sensitivity of 10 eggs per gram of faeces (EPG)) and McMaster (analytical sensitivity of 15 or 50 EPG).For both Mini-FLOTAC and McMaster (analytical sensitivity of 15 EPG), there was a perfect agreement in classifying the efficacy of the anthelmintic as 'normal', 'doubtful' or 'reduced' regardless of pool size. When using the McMaster method (analytical sensitivity of 50 EPG) anthelmintic efficacy was often falsely classified as 'normal' or assessment was not possible due to zero FECs at D0, and this became more pronounced when the pool size increased. In conclusion, pooling ovine faecal samples holds promise as a cost-saving and efficient strategy for assessing GI nematode FECR. However, for the assessment FECR one will need to consider the baseline FEC, pool size and analytical sensitivity of the method. PMID- 27369577 TI - Evaluation of tea tree oil for controlling Rhipicephalus microplus in dairy cows. AB - Our research aimed to test the effects of Melaleuca alternifolia oil (pure and in nanocapsules) in the control of Rhipicephalus microplus in dairy cattle. For this purpose, the in vivo studies used 15 cows distributed in three different groups with the same number of animals. Five cows remained untreated (Group A), representing the control group; other five cows were sprayed with TTO (at 5%) in its pure form (Group B); and five cows were sprayed with nanocapsules of TTO (at 0.75%) (Group C). On days 1 and 4 post-treatments (PT), all cows had their ticks counted. On day 1 PT, two ticks from each cow were collected to evaluate the effect of the treatment on ticks reproduction (in vitro assays). The pure form of TTO caused a significant reduction (P<0.05) in the number of ticks from the Group B compared to the Group A on day 4 PT. However, there was no significant difference in the number of ticks on cows from Groups A and C after treatment (P>0.05). Treatment with TTO in nanocapsules (Group C) interfered with R. microplus reproduction, leading to lower oviposition by female ticks and hatchability (34.5% of efficacy). On the other hand, TTO oil (Group B) did not interfere on ticks reproduction, i.e. showed higher hatchability than the control group. Therefore, it is possible to conclude that pure TTO has an acaricidal effect in dairy cows, in addition to an effect on ticks reproduction when used its nanocapsulated form. PMID- 27369578 TI - Risk factors and molecular typing of Toxoplasma gondii isolated from ostriches (Struthio camelus) from a Brazilian slaughterhouse. AB - Toxoplasma gondii has a worldwide distribution with different genotypes reported in animals and humans. The parasite is of great importance to food production and public health, highlighted by the high diversity of hosts, i.e. ostriches. This study aimed to determine the prevalence of T. gondii infection in ostriches from a Brazilian slaughterhouse, the genotype, and the associated risk factors. T. gondii antibodies were detected in 38/344 (11.05%) serum samples using the modified agglutination test using formalin-fixed tachyzoites (MAT-HS); the parasite was isolated from 14/38 (36.84%) ostrich brain samples using the mouse bioassay; and the DNA was detected from 25/38 (65.79%), using PCR. In farms, the water tank was considered the main risk factor (OR=141.87; p-value<0.05), and oocysts were detected in 30% (6/20) in soil of paddocks before animals were slaughtered (1st sampling), and 40% (8/20) one-year after (2nd sampling) using microscopy and PCR. Non-ostrich fecal samples on the ground resulted negative. Bioassay isolation was confirmed by PCR. All PCR positive samples were sequenced and resulted in 100% homology to Toxoplasma gondii repetitive DNA sequence (GenBank access number EF648168-1). These samples were also typed through RFLP PCR using 11 markers: SAG1, SAG2 (5'-3'SAG2 and alt.SAG2), SAG3, BTUB, GRA6, L358, c22-8, c29-6, PK1, Apico and CS3. Two isolates had a complete genotype, typed from the ostrich tissue. In ostrich samples, the parasite load ranged from 19,043 (TgOsBr1, avirulent) to 54,829 parasitesmL(-1) (TgOsBr2, virulent) using qPCR, whereas soil samples ranged from 11 to 2,275 parasitesmL(-1). Both typed isolates resulted on atypical clones, one previously reported to cause congenital toxoplasmosis in Brazilian patients (TgOsBr1, ToxoDB #206). Thus, these findings support the occurrence of T. gondii in slaughtered ostriches from Brazil, ostriches as sentinel for environmental contamination with T. gondii, the genotypic variability in Brazilian isolates, and the first isolation and genotyping of T. gondii from Brazilian slaughtered ostriches. PMID- 27369579 TI - Heat treatment of serum samples from stray dogs naturally exposed to Dirofilaria immitis and Dirofilaria repens in Romania. AB - Pre-heating of serum samples has been shown to reverse false negative antigen tests for Dirofilaria immitis infection in dogs. Here the authors report the results of serum sampling in a population of dogs naturally exposed to D. immitis and Dirofilaria repens infection by testing in ELISA before and after heat treatment. Of 194 dogs sampled from four cities in Romania, D. immitis circulating antigens were found in 16 (8.2%) non heated samples and in 52 (26.8%) heated samples. Of the 108 dogs examined by Knott test, 24 dogs (22.2%) were positive for circulating mf. Subsequent PCR identification showed six dogs had D. immitis mf only, 12 dogs, had only D. repens mf, and 5 were positive for both. Fifty% of dogs with circulating D. immitis mf had positive antigen tests before and after heating, while the other 50% reverted to positive only after heat treatment. Sixty% of dogs with mixed D. immitis/D. repens infection were antigen positive before and after heating, while the other 40% converted to positive after heating. Antigen testing for D. immitis in the 12 dogs with only D. repens mf gave conflicting results. Only two dogs (16%) were antigen negative both before and after heat treatment. Six dogs (50%) became antigen positive after heating and four dogs (30%) were antigen positive both before and after heat treatment. Results would suggest that: false negative result for antigen testing can be reverted by heating of the serum sample; dogs infected with D. repens may have also an occult infection with D. immitis; heat treatment of serum from D. repens-infected dogs can reveal an occult infection with D. immitis. PMID- 27369580 TI - First genotyping of Cryptosporidium spp. in pre-weaned calves, broiler chickens and children in Syria by PCR-RFLP analysis. AB - In this study, PCR-RFLP was used for the first time in Syria for genotyping Cryptosporidium species of man, calves and chickens. The total of 391 fecal samples included 213 from children with diarrhea (<5years), 67 from pre-weaned calves with diarrhea and 111 from broiler chicken farms. All samples were collected and examined with acid fast stain to detect the positive samples. Subsequently a nested-PCR test was performed on 35 positive samples (17 from calves, 11 from chicken, and 7 from children) targeting SSU rRNA gene, and was followed by RFLP analysis using three restriction enzymes SspI, VspI and MboII. Results showed that C. parvum was the only identified species in children and calves, on the other hand C. baileyi was identified in broilers in addition to another species with unknown RFLP profile in comparison to those which have been described in chicken. Further studies using more genes are needed to sequence and detect subtypes of this parasite. PMID- 27369581 TI - Free-living protozoa in the gastrointestinal tract and feces of pigs: Exploration of an unknown world and towards a protocol for the recovery of free-living protozoa. AB - Associations with free-living protozoa (FLP) have been implicated in the persistence of foodborne pathogenic bacteria in food-related environments. To date however no information is available on the presence of FLP in the gastrointestinal tract (GIT) of pigs, which represents an important reservoir for zoonotic foodborne bacteria and hence a potential location for associations with FLP. This is at least partly due to the lack of adequate protocols to recover FLP from intestinal content and feces. In the present study different protocols to recover FLP from the porcine GIT and feces were tested. The most effective protocols were then applied to explore the presence of live FLP in the pig GIT and feces. A filtration based protocol was identified as the most suitable method to recover viable FLP from the porcine GIT and feces. Cultivable FLP were recovered from different parts of the GIT, suggesting at least a transient presence of FLP in this habitat. Free-living amoebae species (Acanthamoeba spp., Hyperamoeba sp., Vannella sp., Vermamoeba vermiformis, hartmannellids and vahlkampfiids) but also ciliates (Colpoda sp. and Tetrahymena/Glaucoma lookalike) and flagellates (cercomonads, bodonids and glissomonads) were recovered and cultured from pig intestinal content. Acanthamoeba hatchetti and Filamoeba sinensis were isolated for the first time from pig intestinal content. Despite high gastric acidity, non-cyst forming amoeba species were also detected which suggests survival of their trophozoites in the animal GIT. PMID- 27369582 TI - Repellent effects of Melaleuca alternifolia (tea tree) oil against cattle tick larvae (Rhipicephalus australis) when formulated as emulsions and in beta cyclodextrin inclusion complexes. AB - Rhipicephalus australis (formerly Boophilus microplus) is a one host tick responsible for major economic loss in tropical and subtropical cattle production enterprises. Control is largely dependent on the application of acaricides but resistance has developed to most currently registered chemical groups. Repellent compounds that prevent initial attachment of tick larvae offer a potential alternative to control with chemical toxicants. The repellent effects of Melaleuca alternifolia oil (TTO) emulsions and two beta-cyclodextrin complex formulations, a slow release form (SR) and a modified faster release form (FR), were examined in a series of laboratory studies. Emulsions containing 4% and 5% TTO applied to cattle hair in laboratory studies completely repelled ascending tick larvae for 24h whereas 2% and 3% formulations provided 80% protection. At 48h, 5% TTO provided 78% repellency but lower concentrations repelled less than 60% of larvae. In a study conducted over 15 days, 3% TTO emulsion applied to cattle hair provided close to 100% repellency for 2 days, but then protection fell to 23% by day 15. The FR formulation gave significantly greater repellency than the emulsion and the SR formulation from day 3 until the end of the study (P<0.05), providing almost complete repellency at day 3 (99.5%), then decreasing over the period of the study to 49% repellency at day 15. Proof of concept is established for the use of appropriately designed controlled-release formulations to extend the period of repellency provided by TTO against R. australis larvae. PMID- 27369583 TI - Impeding movement of the poultry red mite, Dermanyssus gallinae. AB - The poultry red mite, Dermanyssus gallinae, is an economically important hematophagous parasite of commercial egg laying hens, also affecting domesticated birds and companion animals. Conventional control of D. gallinae through acaricidal spraying is often ineffective, creating an urgent need to identify alternative management strategies for commercial and domestic infestations. Whilst integrated pest management is being considered for D. gallinae, the potential of impeding mite 'migration' routes, to either prevent initial infestation or manage established populations, has not been researched. Here we demonstrate that barriers of insecticidal glue, double sided sticky tape and thyme oil can contain D. gallinae within a specified area of a petri dish (78-88% of total mite population) and this level of containment was significantly greater than for negative controls (p values <0.05). Further studies in poultry houses are recommended to investigate the efficacy of these barriers in real world application and identity potential for barriers as a strategy for mite control. PMID- 27369584 TI - Value of the oral swab for the molecular diagnosis of dogs in different stages of infection with Leishmania infantum. AB - This study was based on the need to employ a sensitive and specific method with samples that could be easily collected for diagnosing dogs infected with Leishmania infantum. To this end, we used real time-PCR (qPCR) to assess the value of the oral swab (OS) in detecting infected sick dogs (SD; n=62), including, for the first time, the analysis of apparently healthy infected dogs (AD; n=30), both from endemic areas for visceral leishmaniasis (VL). For comparison, we also evaluated the performance of the conjunctival swab (CS), blood (BL), lymph node (LN) and serology. We detected the presence of Leishmania DNA in the oral cavity in 62 out of the 92 dogs studied. The OS positivity (67.4%) was equivalent to the CS (68.5%) (p>0.05), higher than BL (52.2%) (p<=0.05), and lower than LN (84.8%) (p<=0.05). OS and CS performed well in SD dogs (82.3% and 83.9%, respectively) but not in AD dogs (36.7% for both samples). BL showed the lowest positivity (52.2%) and provided equivalent results between AD (60.0%) and SD (48.4%) dogs (p>0.05). LN yielded the highest positivity (84.8%), and it was also higher in the SD population (93.5%) compared to the AD population (66.7%) (p<=0.05). Parasite load was high in LN, moderate in OS and CS, and low in BL, showing the relationship between the levels of parasitism and the positivity rates found in these samples. Serology was positive in 82.2% of the SD group and in 70% of the AD dogs (p>0.05). Among the 20 seronegative dogs, seven (35%) were positive in either OS or CS, and 12 (60%) were positive when both noninvasive samples were jointly considered. The OS/CS combination resulted in a significant increase of positivity (p<=0.05) for the AD dogs (from 36.7% to 63.4%), as well as OS/serology (80%) and OS/CS/serology (83.4%). For the SD population, positivity reached up to 95.2% with the same combinations, showing that combination of samples and/or tests is required for the identification of dogs infected with L. infantum and that the OS and CS combination based on qPCR notably improves the detection of both AD and SD dogs. In conclusion, OS proved to be a suitable sample for the molecular diagnosis of infected dogs with clinical signs of VL, but not for dogs with inapparent infection. For these, we recommend the combination of OS results with CS and/or serology in order to reach relevant positivity for L. infantum. Finally, another advantage of using OS or both noninvasive samples is the increased likelihood of diagnosing seronegative dogs. PMID- 27369585 TI - Performance of AlereTM immunochromathographic test for the diagnosis of canine visceral leishmaniasis. AB - The diagnosis and control of canine visceral leishmaniasis (CVL) has fundamental importance in the control of human visceral leishmaniasis. In this context, the immunochromathographic test (ICT) has emerged as a valuable diagnostic tool. Currently, in Brazil, the algorithm for the diagnosis of CVL uses Dual Path Platform (DPP) ICT as a screening test and ELISA as a confirmatory test. However, the DPP((r)) ICT has been facing a problem of insufficient production to meet the national demand. Here, the AlereTM canine visceral leishmaniasis ICT was tested with serum samples from 159 dogs, including symptomatic, asymptomatic and healthy dogs, characterized by DPP((r)) ICT and ELISA (panel A), or ELISA and Indirect Immunofluorescence Assay (IFA) (panel B), and parasitological examination as gold standard. In this study, the AlereTM ICT obtained 0.974 sensitivity for panel A and 0.854 sensitivity for panel B. The specificity was 1.0 for both panels. Thus, the AlereTM ICT has potential to be used for the serological diagnosis of CVL. PMID- 27369586 TI - Efficacy of oral afoxolaner plus milbemycin oxime chewables against induced gastrointestinal nematode infections in dogs. AB - The efficacy of oral afoxolaner plus milbemycin oxime combination chewables against induced gastrointestinal nematode infections in dogs was evaluated in six separate studies. Two studies were performed to evaluate the efficacy of the product against Toxocara canis, two studies evaluated the efficacy against Toxascaris leonina, one study evaluated the efficacy against Ancylostoma braziliense, and one study evaluated the efficacy against Ancylostoma caninum. In the A. caninum study, the efficacy of milbemycin oxime alone and afoxolaner alone was also evaluated. Dogs in all studies were inoculated with infective eggs or larvae and confirmed to have patent infections based on a fecal examination prior to allocation to study group and treatment. Each study utilized a randomized block design with blocks based on pre-treatment body weight. All dogs were assigned to blocks based on body weight, and then each dog within a block was randomly assigned to treatment group. There were two groups of 10 dogs each in the T. canis, T. leonina, and A. braziliense studies: 1) an untreated (control) group and 2) a group treated with afoxolaner plus milbemycin oxime chewables (NexGard Spectra((r)), Merial). This group was treated at a dose as close as possible to the minimum effective dose of afoxolaner and milbemycin oxime (2.5mg+0.5mg per kg body weight, respectively) once on Day 0 using whole chews. There were four groups of 10 dogs each in the A. caninum study: 1) untreated (control), 2) NexGard Spectra((r)) as described above, 3) milbemycin oxime alone (dose of at least 0.5mg per kg of body weight) and 4) afoxalaner alone (dose of at least 2.5mg per kg body weight). For parasite recovery and counts, dogs were euthanized humanely and necropsied seven days after treatment. The efficacy of the afoxolaner plus milbemycin oxime combination was >=98% against T. canis, >=95.8% against T. leonina, and 90.2% against A. braziliense. Efficacy of the combination against A. caninum was 99.7%, while the efficacy of milbemycin oxime alone was 99.6% and the efficacy of afoxolaner alone was 2.1%. Dogs treated with afoxolaner plus milbemycin oxime chewables had significantly (p<=0.0002) fewer nematodes than the untreated controls in all studies. There were no adverse events or other health problems that were related to treatment with Nexgard Spectra((r)) in these studies. The results of these controlled studies demonstrate the high efficacy of the afoxolaner plus milbemycin oxime chewables against a broad range of canine intestinal nematode infections. PMID- 27369587 TI - PCR amplification of a multi-copy mitochondrial gene (cox3) improves detection of Cytauxzoon felis infection as compared to a ribosomal gene (18S). AB - Cytauxzoon felis is a tick-transmitted protozoan parasite that infects felids. Clinical disease caused by acute C. felis infection rapidly progresses in domestic cats, leading to high morbidity and mortality. Accurately diagnosing cytauxzoonosis as soon as possible during acute infection would allow for earlier initiation of antiprotozoal therapy which could lead to higher survival rates. Molecular detection of parasite rRNA genes (18S) by PCR has previously been shown to be a sensitive method of diagnosing C. felis infections. Based on evidence from related apicomplexan species, we hypothesized that C. felis mitochondrial genes would exist at higher copy numbers than 18S and would be a more sensitive diagnostic target. In this study we have designed a PCR assay targeting the C. felis mitochondrial gene cytochrome c oxidase subunit III (cox3). Herein we demonstrate that (1) the cox3 PCR can detect as low as 1 copy of DNA target and can detect C. felis in samples with known mitochondrial sequence heterogeneity, (2) cox3 copy number is increased relative to 18S in blood and tissue samples from acutely infected cats, and (3) the cox3 PCR is more sensitive than 18S PCR for detection of C. felis during early infections. PMID- 27369588 TI - Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations. AB - Orofacial clefts (OFCs) are congenital dysmorphologies of the human face and oral cavity, with a global incidence of 1 per 700 live births. These anomalies exhibit a multifactorial pattern of inheritance, with genetic and environmental factors both playing crucial roles. Many loci have been implicated in the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations of Asian and European ancestries, through genome-wide association studies and candidate gene studies. However, few populations of African descent have been studied to date. Here, the authors show evidence of an association of some loci with NSCL/P and nonsyndromic cleft palate only (NSCPO) in cohorts from Africa (Ghana, Ethiopia, and Nigeria). The authors genotyped 48 single-nucleotide polymorphisms that were selected from previous genome-wide association studies and candidate gene studies. These markers were successfully genotyped on 701 NSCL/P and 163 NSCPO cases, 1,070 unaffected relatives, and 1,078 unrelated controls. The authors also directly sequenced 7 genes in 184 nonsyndromic OFC (NSOFC) cases and 96 controls from Ghana. Population-specific associations were observed in the case-control analyses of the subpopulations, with West African subpopulations (Ghana and Nigeria) showing a similar pattern of associations. In meta-analyses of the case-control cohort, PAX7 (rs742071, P = 5.10 * 10(-3)), 8q24 (rs987525, P = 1.22 * 10(-3)), and VAX1 (rs7078160, P = 0.04) were nominally associated with NSCL/P, and MSX1 (rs115200552, P = 0.01), TULP4 (rs651333, P = 0.04), CRISPLD2 (rs4783099, P = 0.02), and NOG1 (rs17760296, P = 0.04) were nominally associated with NSCPO. Moreover, 7 loci exhibited evidence of threshold overtransmission in NSOFC cases through the transmission disequilibrium test and through analyses of the family-based association for disease traits. Through DNA sequencing, the authors also identified 2 novel, rare, potentially pathogenic variants (p.Asn323Asp and p.Lys426IlefsTer6) in ARHGAP29 In conclusion, the authors have shown evidence for the association of many loci with NSCL/P and NSCPO. To the best of this knowledge, this study is the first to demonstrate any of these association signals in any African population. PMID- 27369589 TI - Full Spectrum of Postnatal Tooth Phenotypes in a Novel Irf6 Cleft Lip Model. AB - Clefting of the lip, with or without palatal involvement (CLP), is associated with a higher incidence of developmental tooth abnormalities, including hypodontia and supernumerary teeth, aberrant crown and root morphologies, and enamel defects, although the underlying mechanistic link is poorly understood. As most CLP genes are expressed throughout the oral epithelium, the authors hypothesized that the expression of CLP genes may persist in the dental epithelium and thus, in addition to their earlier role in labiopalatine development, may play an important functional role in subsequent tooth patterning and amelogenesis. To address this, the authors generated a unique conditional knockout model involving the major CLP gene, Irf6, that overcomes the previously reported perinatal lethality to enable assessment of any posteruption dental phenotypes. A dental epithelium-specific Irf6 conditional knockout (Irf6-cKO) mouse was generated via a Pitx2-Cre driver line. Dental development was analyzed by microcomputed tomography, scanning electron microscopy, histology, immunohistochemistry, and quantitative polymerase chain reaction. Irf6-cKO mice displayed variable hypodontia, occasional supernumerary incisors and molars, as well as crown and root patterning anomalies, including peg-shaped first molars and taurodontic and C-shaped mandibular second molars. Enamel density was reduced in preeruption Irf6-cKO mice, and some shearing of enamel rods was noted in posteruption incisors. There was also rapid attrition of Irf6-cKO molars following eruption. Histologically, Irf6-cKO ameloblasts exhibited disturbances in adhesion and polarity, and delayed enamel formation was confirmed immunohistochemically. Altered structure of Hertwig's epithelial root sheath was also observed. These data support a role for IRF6 in tooth number, crown and root morphology and amelogenesis that is likely due to a functional role of Irf6 in organization and polarity of epithelial cell types. This data reinforce the notion that various isolated tooth defects could be considered part of the CLP spectrum in relatives of an affected individual. PMID- 27369591 TI - [Not Available]. PMID- 27369592 TI - [Not Available]. PMID- 27369590 TI - Changing housework, changing health? A longitudinal analysis of how changes in housework are associated with functional somatic symptoms. AB - AIM: The aim of this study was to analyse how changes in housework over the course of adulthood are related to somatic health in Swedish men and women. METHODS: Data were drawn from 2 waves of the Northern Swedish Cohort Study, response rate 94.3%, N=1,001. A subsample of cohabiting individuals was selected (n=328 women, 300 men). Outcome variable was functional somatic symptoms (FSS) at age 42. Associations were assessed in multivariate general linear models with adjustment for confounders and somatic health at age 30. RESULTS: Housework is primarily performed by women, and women's responsibility for and performance of housework increased from ages 30 to 42. These changes were associated with elevated levels of FSS at age 42 in women. Men reported considerably lower responsibility for and performed less housework compared with women, the load of housework for men does not change substantially from ages 30 to 42 and no associations with FSS were identified. CONCLUSIONS: The gendered division of housework means that women are particularly exposed to a heavy workload. Women's responsibility for and performance of housework increase between ages 30 and 42 and this threatens to be embodied in the form FSS. We conclude that housework should be considered an important source of stress in addition to that from waged work and that a deeper understanding of the links between housework and health requires a gender theoretical analysis. PMID- 27369593 TI - [Not Available]. PMID- 27369594 TI - [Not Available]. PMID- 27369595 TI - [Not Available]. PMID- 27369597 TI - [Not Available]. PMID- 27369596 TI - [Not Available]. PMID- 27369598 TI - [Not Available]. PMID- 27369600 TI - [Not Available]. PMID- 27369599 TI - [Not Available]. PMID- 27369601 TI - [Not Available]. PMID- 27369602 TI - [Not Available]. PMID- 27369604 TI - [Not Available]. PMID- 27369603 TI - [Not Available]. PMID- 27369605 TI - [Not Available]. PMID- 27369607 TI - [Not Available]. PMID- 27369606 TI - [Not Available]. PMID- 27369608 TI - [Not Available]. PMID- 27369609 TI - [Not Available]. PMID- 27369610 TI - [Not Available]. PMID- 27369611 TI - [Not Available]. PMID- 27369612 TI - [Not Available]. PMID- 27369613 TI - [Not Available]. PMID- 27369615 TI - [Not Available]. PMID- 27369614 TI - [Not Available]. PMID- 27369617 TI - [Not Available]. PMID- 27369616 TI - [Not Available]. PMID- 27369618 TI - [Not Available]. PMID- 27369619 TI - [Not Available]. PMID- 27369620 TI - [Not Available]. PMID- 27369622 TI - [Not Available]. PMID- 27369621 TI - [Not Available]. PMID- 27369623 TI - [Not Available]. PMID- 27369624 TI - [Not Available]. PMID- 27369625 TI - [Not Available]. PMID- 27369626 TI - [Not Available]. PMID- 27369627 TI - [Not Available]. PMID- 27369628 TI - [Not Available]. PMID- 27369629 TI - [Not Available]. PMID- 27369630 TI - [Not Available]. PMID- 27369631 TI - [Not Available]. PMID- 27369632 TI - [Not Available]. PMID- 27369634 TI - [Not Available]. PMID- 27369633 TI - [Not Available]. PMID- 27369635 TI - Mandibular Jaw Bone Regeneration Using Human Dental Cell-Seeded Tyrosine-Derived Polycarbonate Scaffolds. AB - Here we present a new model for alveolar jaw bone regeneration, which uses human dental pulp cells (hDPCs) combined with tyrosine-derived polycarbonate polymer scaffolds [E1001(1k)] containing beta-tricalcium phosphate (beta-TCP) [E1001(1k)/beta-TCP]. E1001(1k)/beta-TCP scaffolds (5 mm diameter * 1 mm thickness) were fabricated to fit a 5 mm rat mandibular ramus critical bone defect. Five experimental groups were examined in this study: (1) E1001(1k)/beta TCP scaffolds seeded with a high density of hDPCs, 5.0 * 10(5) hDPCs/scaffold (CH); (2) E1001(1k)/beta-TCP scaffolds seeded with a lower density of hDPCs, 2.5 * 10(5) hDPCs/scaffold (CL); (3) acellular E1001(1k)/beta-TCP scaffolds (SA); (4) acellular E1001(1k)/beta-TCP scaffolds supplemented with 4 MUg recombinant human bone morphogenetic protein-2 (BMP); and (5) empty defects (EDs). Replicate hDPC seeded and acellular E1001(1k)/beta-TCP scaffolds were cultured in vitro in osteogenic media for 1 week before implantation for 3 and 6 weeks. Live microcomputed tomography (MUCT) imaging at 3 and 6 weeks postimplantation revealed robust bone regeneration in the BMP implant group. CH and CL groups exhibited similar uniformly distributed mineralized tissue coverage throughout the defects, but less than the BMP implants. In contrast, SA-treated defects exhibited sparse areas of mineralized tissue regeneration. The ED group exhibited slightly reduced defect size. Histological analyses revealed no indication of an immune response. In addition, robust expression of dentin and bone differentiation marker expression was observed in hDPC-seeded scaffolds, whereas, in contrast, BMP and SA implants exhibited only bone and not dentin differentiation marker expression. hDPCs were detected in 3-week but not in 6 week hDPC-seeded scaffold groups, indicating their survival for at least 3 weeks. Together, these results show that hDPC-seeded E1001(1k)/beta-TCP scaffolds support the rapid regeneration of osteo-dentin-like mineralized jaw tissue, suggesting a promising new therapy for alveolar jaw bone repair and regeneration. PMID- 27369637 TI - [Not Available]. PMID- 27369638 TI - [Not Available]. PMID- 27369636 TI - Biomechanical effects of morphological variations of the cortical wall at the bone-cement interface. AB - BACKGROUND: The integrity of bone-cement interface is very important for the stabilization and long-term sustain of cemented prosthesis. Variations in the bone-cement interface morphology may affect the mechanical response of the shape closed interlock. METHODS: Self-developed new reamer was used to process fresh pig reamed femoral canal, creating cortical grooves in the canal wall of experimental group. The biomechanical effects of varying the morphology with grooves of the bone-cement interface were investigated using finite element analysis (FEA) and validated using companion experimental data. Micro-CT scans were used to document interlock morphology. RESULTS: The contact area of the bone cement interface was greater (P < 0.05) for the experimental group (5470 +/- 265 mm(2)) when compared to the specimens of control group (5289 +/- 299 mm(2)). The mechanical responses to tensile loading and anti-torsion showed that the specimens with grooves were stronger (P < 0.05) at the bone-cement interface than the specimens without grooves. There were positively significant correlation between the contact area and the tensile force (r (2) = 0.85) and the maximal torsion (r (2) = 0.77) at the bone-cement interface. The volume of cement of the experimental group (7688 +/- 278 mm(3)) was greater (P < 0.05) than of the control group (5764 +/- 186 mm(3)). There were positively significant correlations between the volume of cement and the tensile force (r (2) = 0.90) and the maximal torsion (r (2) = 0.97) at the bone-cement interface. The FEA results compared favorably to the tensile and torsion relationships determined experimentally. More cracks occurred in the cement than in the bone. CONCLUSIONS: Converting the standard reaming process from a smooth bore cortical tube to the one with grooves permits the cement to interlock with the reamed bony wall. This would increase the strength of the bone-cement interface. PMID- 27369639 TI - [Not Available]. PMID- 27369640 TI - [Not Available]. PMID- 27369641 TI - [Not Available]. PMID- 27369642 TI - [Not Available]. PMID- 27369643 TI - Immunogenicity of tocilizumab in patients with rheumatoid arthritis. AB - OBJECTIVE: The immunogenicity of tocilizumab (TCZ) has been poorly studied. We assessed the immunogenicity of TCZ and serum TCZ trough levels in rheumatoid arthritis (RA) patients and the preexisting TCZ-specific CD4+ T cell repertoire in healthy controls. METHODS: Anti-drug antibodies (ADAs) to TCZ and serum TCZ trough levels in RA patients were assessed at different times by ELISA. Frequencies of naive anti-TCZ CD4+ precursors were studied in healthy controls. RESULTS: In total, 91 samples from 40 RA patients were analyzed: 21 patients within the first 6 months after treatment initiation and 19 during follow-up after a mean TCZ treatment duration of 21+/-13 months. None of the 91 samples showed persistent ADAs to TCZ. Only 3 RA patients showed transient and low titers of anti-TCZ ADAs. Serum TCZ trough levels were associated with neither patient characteristics (gender, body mass index) nor disease activity and were identical for patients with and without co-treatment with methotrexate. Three of 9 healthy donors showed preexisting TZC-specific CD4+ T cells at a low level. CONCLUSION: Serum TCZ trough levels were not affected by patient characteristics. The occurrence of ADAs to TCZ was a rare event. Because healthy donors show the same frequency of naive TCZ-specific and infliximab-specific CD4+ T cell precursors, the low prevalence of ADAs to TCZ might result from interleukin-6 blockade. PMID- 27369644 TI - Collection and management of selected comorbidities and their risk factors in chronic inflammatory rheumatic diseases in daily practice in France. AB - INTRODUCTION: In chronic inflammatory rheumatic diseases (CIRDs), comorbidities such as cardiovascular disease and infections are sub-optimally managed. EULAR recently developed points to consider to collect and report comorbidities. The objective of this present study was to develop a pragmatic guide to collect, report and propose management recommendations for comorbidities, from a rheumatologist perspective. METHODS: The collection and reporting of comorbidities and risk factors was adapted from the EULAR points to consider. To develop management recommendations, the process comprised (1) systematic literature reviews by 3 fellows and (2) a 2-day consensus process involving 110 experts (rheumatologists and health professionals). Votes of agreement (Likert 1 5 where 5 indicates full agreement) were obtained. RESULTS: The six selected comorbidities were ischemic cardiovascular diseases, malignancies, infections, diverticulitis, osteoporosis and depression. The literature review retrieved 97 articles or websites, mostly developed for the general population. The consensus process led to reporting presence of comorbidities, current treatment, risk factors (e.g. hypertension), screening (e.g. mammography) and prevention (e.g. vaccination). Management recommendations include physical examination (e.g. blood pressure or lymph node examination), prescribing screening procedures, and interpreting results to refer in a timely manner to appropriate other health professionals. Agreement was high (mean+/-standard deviation, 4.37+/-0.33). CONCLUSIONS: Using an evidence-based approach followed by expert consensus, this initiative furthers the dissemination in France of the EULAR points to consider, and clearly defines what part of the management of comorbidities is potentially within the remit of rheumatologists. This initiative should facilitate systematic management of patients with CIRDs. PMID- 27369645 TI - Serum levels of Dkk-1, sclerostin and VEGF in patients with ankylosing spondylitis and their association with smoking, and clinical, inflammatory and radiographic parameters. AB - OBJECTIVE: To evaluate serum Dickkopf-1 (Dkk-1), sclerostin and vascular endothelial growth factor (VEGF) levels in patients with ankylosing spondylitis (AS) compared to healthy controls as well as their association with smoking, and clinical, inflammatory and radiographic parameters. METHODS: Serum samples for total Dkk-1, sclerostin and VEGF were obtained from 57 tumour necrosis factor (TNF) inhibitor naive patients with AS and 34 sex-, age- and body mass index (BMI)-matched controls. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), modified Stroke AS Spine Score (mSASSS) and smoking status were assessed for each patient. RESULTS: There was no significant difference in serum bone metabolism markers between AS patients and controls. Dkk-1 levels were significantly (P<0.05) higher in AS patients with elevated ESR and CRP and no syndesmophytes, and were significantly (P<0.001) correlated with sclerostin levels (r=0.592). VEGF levels were significantly (P<0.05) higher in AS patients with current and ever smoking, elevated ESR and CRP, and high BASDAI and BASFI, and were significantly (P<0.05) correlated with ESR (r=0.284), CRP (r=0.285), BASDAI (r=0.349) and BASFI (r=0.275). In multivariate regression analyses, high Dkk-1 levels were significantly (P<=0.001) associated with elevated ESR and CRP, no syndesmophytes and high sclerostin levels, and high VEGF levels significantly (P<0.05) with ever smoking, and elevated ESR and CRP. CONCLUSION: In AS, serum Dkk-1 concentrations appear to be related not only to syndesmophyte formation but also to systemic inflammation. Furthermore, high VEGF levels may be associated with smoking exposure. PMID- 27369646 TI - First case of osteopathia striata with cranial sclerosis in an adult male with Klinefelter syndrome. AB - Osteopathia striata with cranial sclerosis is a rare X-linked disorder. It is often lethal in male patients, and is considered X-linked dominant since affected females exhibit clinical signs, although milder than males. We describe here an adult male patient, with clinical and radiological signs similar to those described in female patients. Diagnosis was confirmed by the identification of an AMER1 mutation. The presence of long bones striation and the clinical phenotype of the patient also led to the diagnosis of non-mosaic Klinefelter syndrome, probably explaining the non-lethal and even rather minor phenotype compared to the rare affected males already described. PMID- 27369647 TI - Ultrasound can be useful to predict an evolution towards rheumatoid arthritis in patients with inflammatory polyarthralgia without anticitrullinated antibodies. AB - INTRODUCTION: Ultrasound (US) subclinical synovitis in prerheumatoid arthritis (RA) patients has been demonstrated in anticitrullinated antibodies (ACPA) positive patients to be predictive for future development of RA. The aim of the study was to assess the value of the US as a predictive factor for the future development of RA in patients with polyarthralgia without ACPA. METHOD: Eighty consecutive ACPA-patients with polyarthralgia without clinical synovitis or ACPA before the US examination were included. To detect significant US synovitis, we applied the criteria of a US score (SONAR) validated among RA patients and controls. The diagnosis of RA was based on the ACR/EULAR criteria. RESULTS: Significant US synovitis were present at baseline in 20 (25%) of the patients. The mean (SD) follow-up time was 18 (7) months in both groups. Seven (9%) patients developed a clear RA and 2 another inflammatory arthritis. US synovitis at baseline was significantly associated with evolution to RA: 5/20 (25%) versus 2/60 (3%) (P<0.05). The free time to RA was significantly shorter when US synovitis were present (P<0.01). Moreover, after multivariate analysis, US appeared to be the only independent predictor of an evolution to RA (OR: 7.4). Results remained similar after including all patients developing another inflammatory arthritis. CONCLUSIONS: Our study suggests that US can be used as a predictor for the evolution to RA or other inflammatory arthritis in patients presenting polyarthralgia without ACPA. PMID- 27369648 TI - Tooth-brushing: An impact on rheumatoid arthritis. PMID- 27369650 TI - Efficacy of denosumab combined with bDMARDs on radiographic progression in rheumatoid arthritis. PMID- 27369649 TI - Association of TRAF1-C5 with risk of uveitis in juvenile idiopathic arthritis. AB - OBJECTIVES: Numerous single nucleotide polymorphisms (SNPs) have been associated with JIA, but few of these studies were replicated. We conducted a candidate-gene approach study to assess if some SNPs could be related to clinical subtypes or other clinical features of the juvenile idiopathic arthritis (JIA) such as the risk of uveitis, ANA positivity and the age at onset. METHODS: SNPs in six genes were analysed: PTPN22, STAT4, TRAF1-C5, TGFbeta, TNFAIP3, and C12orf30. We retrospectively included 104 JIA patients, fulfilling the ILAR classification criteria. Association between SNPs and JIA clinical subtypes, the presence of ANA, risk of uveitis and age at onset was evaluated using a Chi2 test or a Fischer test. RESULTS: No associations between different clinical subtypes as well as presence of ANA and the 6 SNPs were found. However, the AA genotype of TRAF1-C5 appeared associated in a subgroup of patients with uveitis in oligoarticular and polyarticular forms [OR 3.77 (95% CI: 1.1067, 12.8527); P=0.066]. Furthermore, AA TRAF1-C5 was significantly more frequent in antinuclear antibodies (ANA) positive patients presenting uveitis, compared to patients without uveitis and without ANA (P<0.05). CONCLUSION: TRAF1-C5 genotype could identify JIA patients with a risk to develop uveitis especially in oligo and polyarticular forms and among ANA-positive children. Given the moderate size of our cohort, this association has to be confirmed in other studies. PMID- 27369651 TI - Omalizumab in the treatment of antihistamine-resistant chronic urticaria in adults. PMID- 27369652 TI - Paracetamol-induced fixed drug eruption in a patient with recurrent fever and rash. PMID- 27369653 TI - [Not Available]. PMID- 27369655 TI - [Not Available]. PMID- 27369654 TI - [Not Available]. PMID- 27369656 TI - [Not Available]. PMID- 27369657 TI - [Not Available]. PMID- 27369659 TI - [Not Available]. PMID- 27369658 TI - [Not Available]. PMID- 27369660 TI - [Not Available]. PMID- 27369662 TI - [Not Available]. PMID- 27369661 TI - [Not Available]. PMID- 27369663 TI - [Not Available]. PMID- 27369664 TI - [Not Available]. PMID- 27369665 TI - [Not Available]. PMID- 27369666 TI - [Not Available]. PMID- 27369667 TI - [Not Available]. PMID- 27369669 TI - [Not Available]. PMID- 27369668 TI - [Not Available]. PMID- 27369670 TI - [Not Available]. PMID- 27369672 TI - [Not Available]. PMID- 27369671 TI - [Not Available]. PMID- 27369673 TI - [Not Available]. PMID- 27369674 TI - [Not Available]. PMID- 27369675 TI - [Not Available]. PMID- 27369676 TI - [Not Available]. PMID- 27369678 TI - [Not Available]. PMID- 27369677 TI - [Not Available]. PMID- 27369679 TI - [Discrepancy Between Subjective Memory Complaints and Objective Memory Deficits in Elderly Patients with Depression Compared to Mild Cognitive Impairment]. AB - OBJECTIVE: Since depression in the elderly usually presents with memory complaints and may impair memory functions, differential diagnosis of cognitive impairment is quite difficult. This study aimed to investigate the discrepancy between subjective memory complaints (SMC) and objective memory deficits in elderly patients with major depressive disorder (MDD) and mild cognitive impairment (MCI). METHOD: The study sample consisted of 30 elderly patients with a diagnosis of MCI (according to Petersen- Mayo criteria) and 29 with a diagnosis of DSM-IV-TR MDD who were admitted to the outpatient geriatric psychiatry clinic. The control group (HC) consisted of 30 healthy elderly volunteers. Turkish versions of the Mini Mental State Examination (MMSE), Clock Drawing Test (CDT), ADAS-Cog, Subjective Memory Complaints Questionnaire (SMCQ) and Geriatric Depression Scale (GDS) were administered to all participants. RESULTS: The SMCQ scores of both MDD and MCI patients were higher than HC. However, there was no difference between HC and MDD groups in terms of the MMSE, the CDT and the ADAS Cog scores. CONCLUSION: In elderly patients, subjective memory complaints do not seem to differentiate between depression and cognitive impairment. However, the discrepancy between SMC and cognitive performances suggest depression rather than a cognitive impairment. Further longitudinal studies should investigate the role of SMC in future cognitive impairment for elderly patients with depression. PMID- 27369680 TI - [The Relationship of Verbal Working Memory and Theory of Mind in First Degree Relatives of Patients With Schizophrenia and Bipolar Disorder]. AB - OBJECTIVE: We aimed to compare Theory of Mind (ToM) functions and investigate the relationship between ToM functions and verbal working memory (VWM) in first degree relatives of bipolar disorder and schizophrenia patients. METHOD: The sample consisted of first degree relatives of patients with bipolar disorder (n=22), schizophrenia (n=28), and age, gender, education and total IQ matched healthy volunteers (n=27) without a family history of schizophrenia or bipolar disorder. We administered Auditory Consonants Test (ACT) to evaluate VWM, first and second order false belief tests (ToM-1, ToM-2), Faux Pas Test (FPT), Hinting Test (HT) to evaluate different domains of ToM functions. RESULTS: Both relative groups performed significantly lower in all components of ToM and VWM tests compared to the control group. When VWM scores were employed as covariate in the analyses, the FPT difference between the groups remained significant, HT difference regressed to a marginal level, and the difference between ToM-1 and ToM-2 disappeared. CONCLUSION: To our knowledge, this is the first study indicating the presence of ToM impairment among first degree relatives of bipolar disorder patients similar to relatives of schizophrenia patients. VWM performance seems to affect first and second order ToM functions in relatives of patients with schizophrenia and bipolar disorder. On the other hand, FPT and HT domains seem to be independent of VWM performances in these groups. FPT and HT impairments may be familial vulnerability markers that are independent from neurocognitive impairment. PMID- 27369681 TI - [The Relationship Between Anger Expression, Body Image and Eating Attitudes in Social Anxiety Disorder]. AB - OBJECTIVE: The aim of the present study was to investigate both the prevalence of social anxiety disorder (SAD) and itsassociation of trait anger and anger expression, eating attitudes and body perceptions in university students having the said disorder. METHOD: One thousand students from Cumhuriyet University were included in the study. During the initial stage, Liebowitz Social Anxiety Scale (LSAS) and socio-demographic data form were administered to the students. Those obtaining 30 points or more in LSAS were called for a psychiatric interview. The students diagnosed with social anxiety disorder (n=87) and the control group (n=87) were administered Eating Attitude Test (EAT), Multidimensional Body-Self Relations Questionnaire (MBSRQ) and The State Trait Anger Scale (STAXI). RESULTS: The point prevalence of social anxiety disorder was found to be 9.4% in those attending the study. Trait anger, anger-in and anger-out scores were statistically significantly higher; anger control and multidimensional body-self relations scale points were statistically lower at the SAB group when compared to the control group. The MBSRQ scores correlated negatively, while the EAT scores correlated positively, with anger-in scores in students with SAD. CONCLUSION: SAD is a common disorder in university students. Our study, showed that repressed anger could adversely affect body image and eating behaviors in SAD. In students having social anxiety disorder, approaches aiming at appropriate anger expression and positive body perception may yield positive results to treatment in students with SAD. PMID- 27369682 TI - [Does Emotional Context Affect Subliminal and Supraliminal Priming?]. AB - OBJECTIVE: Emotions are complex psychophysiological changes experienced during the interactions of internal and external processes. The stimuli that have emotional value have processing efficiency both in encoding and retrieval processes with respect to the neutral stimuli. Processing advantage is present also for implicit memory. Priming effect does not require conscious recollection and leads to changes in responding due to previous exposure to the stimulus. In this study, it was aimed to investigate the effect of presentation type and different emotional contexts on the priming. METHOD: Sixty-volunteered-university students were (Female: n=40, X age=19.03+/-1.23; Male: n=20, X age=19.70+/-1.92) randomly assigned to the experimental conditions. Presentation type (Subliminal and Supraliminal) was between subject and Emotional Context (pleasant, neutral, and unpleasant pictures) was within subject independent variables. Dependent variables were Word Stem Completion score and completion latencies. RESULTS: Unpleasant emotional context had more capacity to create priming effect than the other emotional contexts. Both Subliminal and Supraliminal conditions favored the priming. Controversially to the transfer appropriate processing approach, the priming effect that was produced by supraliminal condition significantly higher than the priming created by the subliminal condition. CONCLUSION: Unpleasant picture context produced more priming due to reason that evolutionarily important, i.e. thread-related, stimuli have processing priority and they capture the attention, utilize other cognitive resources easily. Even in priming, that is a phenomenon based heavily on data driven processes, concept driven processes are also effectual as indicated by levels-of-processing approach. PMID- 27369683 TI - [Analyzing the Wechsler Intelligence Scale for Children-Revised (WISC-R) in Children With Attention Deficit and Hyperactivity Disorder: Predictive Value of Subtests, Kaufman, and Bannatyne Categories]. AB - OBJECTIVE: The aim of this study is to evaluate the predictive value of intelligence quotients scores (IQs), subtests of Wechsler Intelligence Scale for Children-Revised (WISC-R) and Kaufman's and Bannatyne's categories scores which are the sums of subtests of WISC-R in attention deficit hyperactivity disorder (ADHD). Another aim is to examine the difference of some neurocognitive skills between the children with ADHD and their unaffected peers by WISC-R subtests. METHOD: WISC-R's subtest and IQ scores, and scores of Kaufman's and Bannatyne's categories of the children who were diagnosed with only ADHD were compared with the same scores of the children who were in healthy control group (N= 111) and were in ADHD with co morbidity group (N= 82). RESULTS: It was found that the subtest scores (vocabulary, comprehension, digit span, picture completion and block design) of the children with only ADHD and ADHD with comorbidity were significantly lower than healthy group. It was observed that subtests of comprehension (Wald= 5.47, df= 1, p=0.05), digit span (Wald= 16.79, df= 1, p=0.001) and picture completion (Wald= 5.25, df= 1, p=0.05) predicted significantly ADHD. In addition, the categories of freedom from distractibility (Wald= 8.22, df= 1, p=0.01) and spatial abilities (Wald= 12.22, df= 1, p<0.0001) were predictive for ADHD in this study. CONCLUSION: Problem solving abilities in social processes, auditory short-term memories, visual-spatial abilities and visual configuration abilities of the children with ADHD was observed to be lower than their healthy peers. It was thought that in WISC-R's profile analysis, the categories of freedom from distractibility and spatial abilities can be distinctive in ADHD diagnose. PMID- 27369684 TI - [Validity and Reliability Studies of Modified Mini Mental State Examination (MMSE E) For Turkish Illiterate Patients With Diagnosis of Alzheimer Disease]. AB - OBJECTIVE: To investigate the validity and reliability of modified Mini Mental State Examination (MMSE-E) for illiterate patients in a Turkish population with Alzheimer's disease (AD). METHOD: A total of 107 illiterate patients with Alzheimer's Disease (women: 65, men: 42) and 68 illiterate healthy volunteer subjects (women: 36, men: 32) were included in the study. MMSE-I and Geriatrics Depression Scale were performed on all subjects, Alzheimer patients were also administered Basic Activities of Daily Living (B- ADL). Clinical Dementia Rating (CDR) was used to determine the severity of disease, while a receiver operating characteristic (ROC) analysis was performed to analyze the cut-off scores of MMSE I, and the positive/negative predictive values that were calculated for the optimal cut-off scores. Internal consistency was measured using Cronbach's coefficient ?. Additionally, correlations between total MMSE-I score and the CDR, B-ADL, and GDS scores were examined. RESULTS: The MMSE-I scores significantly and inversely correlated with CDR (-0.82, p=0.000) and B-ADL scores (-0.051, p=0.000). The optimal cut-off points of MMSE-I were 23/24, which yielded a sensitivity of 99.0% - %100.0, a specificity of 98.5% - 97.0%, and an AUC of 1.0/1.0, respectively. Reliability of the MMSE-I was high alpha = 0.70). CONCLUSION: The total MMSE-I score was able to differentiate the AD group from the control group. PMID- 27369685 TI - [The Effect of Tele-Nursing Practices to the Schizophrenia Patient Care: A Systematic Review]. AB - OBJECTIVE: This study is a systematic review that was conducted in an attempt to evaluate the tele-nursing interventions being used in the schizophrenia patient care and the efficiency of these interventions. METHOD: The study was conducted by checking the Pubmed, Cinahl, Science Direct, Wiley Interscience, Ulakbim Medicine Database and the Turkish Medline database. The English keywords were translated with "nursing by telephone" that is the only term involved in the MeSH (Medical Subject Headings) index for English keywords and TST (Turkish Scientific Terms) for Turkish keywords. A total of six articles that met the inclusion criteria were involved in the evaluation. RESULTS: According to the study findings that were evaluated within the scope of the systematic review, it was observed that the tele-nursing interventions were limited with Telephone Intervention Problem Solving-TIPS. It was determined that the TIPS intervention extended the time spent by schizophrenia patients in society and decreased the duration of days being spent at the hospital after every rehospitalization and the number of applications for rehospitalization. It was also observed to increase the adherence to the psychiatric medication and social functioning, decrease the level of psychiatric symptoms after the discharge. Besides, the face to-face interviews being conducted before the TIPS intervention were observed to develop the verbal communication skills of patients. CONCLUSION: According to this systematic review, the quantitative limitation of relevant studies is limited with the phone applications of tele-nursing interventions; however, it has positive results. PMID- 27369686 TI - [Augmentation of Clozapine With Paliperidone in Schizophrenia Patients With Partial Response to Treatment: A Case Series]. AB - Clozapine is the only antipsychotic which has definitely shown to be effective in refractory schizophrenia. Clozapine treatment is usually preferred in schizophrenia patients with a partial response to treatment and augmentation strategies are tried when clozapine also fails to provide full treatment response. In treatment resistant schizophrenia patients addition of a second antipsychotic is a frequently preferred augmentation method. With previous augmentation strategies consistent positive results could not be obtained. Paliperidone is a risperidone metabolite and it has proven effectiveness in schizophrenia treatment. Although most effects of paliperidone on central nervous system are similar with risperidone, there are some differences. In this case series treatments of 5 schizophrenia patients who still had symptoms despite clozapine treatment were augmented with paliperidone during 6 months of follow up. This augmentation was tolerated well by the patients, and caused improvements in both positive and negative symptoms. Particularly, improvement in negative symptoms after addition of paliperidone was remarkable in our patients. Evaluation of paliperidone's effects on negative symptoms in schizophrenia patients with partial response to clozapine treatment using randomized, placebo controlled studies may provide an important treatment choice. PMID- 27369687 TI - [Synthetic Cannabinoid Receptor Agonist-Associated Psychotic Disorder: A Case Report]. AB - Synthetic cannabinoid receptor agonists (SCRA) has become one of the most abused substances, recently. JWH-018 street name known as Bonzai is one of the most abused substances in Turkish Republic of Northern Cyprus. The most common symptoms in cases reported with synthetic cannabis use are agitation, angry, paranoia and reference delusions, disorientation, seizure and nausea. Although the effects are very similar to cannabis, stimulant effects are more likely in SCRA use. In preparations containing SCRA do not contain cannabinidol agent which is reported to reduce the psychotic effects of the cannabis. This may explain the relationship between SCRA and psychotic disorders. We aimed to discuss a brief psychotic disorder associated with SCRA use and treatment which is less reported in the literature in this case report. PMID- 27369688 TI - [Duloxetine-Induced Hypertension: A Case Report]. AB - Duloxetine, a serotonin-norepinephrine reuptake inhibitor, is used for diabetic neuropathic pain and fibromyalgia as well as major depressive disorder. Serotonin norepinephrine reuptake inhibitors may lead to increased blood pressure via their noradrenergic effects in addition to their cardiovascular side effects. In this paper, we report a case with increased blood pressure after the initiation of duloxetine that recovered by discontinuation of the medication. PMID- 27369689 TI - [Editorial]. PMID- 27369690 TI - Patient Recall, Interpretation, and Perspective of an Inconclusive Long QT Syndrome Genetic Test Result. AB - Patients' perceptions of inconclusive results have been previously investigated in cancer genetics. The differences in how patients recall and interpret an uninformative test result compared to a known pathogenic result can affect medical decisions post disclosure. However, there is little to no data available on patients' interpretation and perception of uninformative genetic results in inherited heart disease. We report the results of a qualitative analysis of 16 telephone interviews with participants who received a negative or a variant of unknown significance (VUS) result from Long QT syndrome (LQTS) genetic testing. Our results suggest that the type of result (negative versus VUS) does not affect recall, regardless of the reason for testing. When receiving a negative result, a majority of participants appropriately perceived no change in their diagnosis, while the perception of risk for family members varied. The majority of participants felt they maintained an awareness of their condition after the result disclosure, and that clinical follow-up was similar to that planned prior to the genetic test result. Further work is needed to determine if there are any differences between obtaining a VUS result versus a negative result in this population. PMID- 27369691 TI - Erratum to: Bilateral vestibular hypofunction and Lyme disease: a causal link? PMID- 27369692 TI - Minimal EEG montage with high yield for the detection of status epilepticus in the setting of postanoxic brain damage. AB - For the diagnosis of electrographic seizures or status epilepticus, we reduced the number of EEG-electrodes to make urgent EEG monitoring more feasible. Unlike the current existing research, with mixed results, we studied a specific population with postanoxic brain damage, expecting a higher yield of detection of ictal EEG patterns. In a population treated with therapeutic hypothermia post cardiac arrest, the initial EEGs were reformatted in a longitudinal, a hairline and an 8-lead montage, and independently reviewed by two investigators. The EEGs were categorized into three categories: one without ictal EEG activity, one with interictal activity and one with probable electrographic seizure(s). Generalized ictal EEG activity was the most frequently observed EEG pattern. The average sensitivity for the detection of probable electrographic seizure(s) was 100 % for the 8-lead montage and 92 % in the hairline montage. In comparison to the routine longitudinal montage, the 8-lead montage proved to be reliable for the detection of electrographic seizure activity in a postanoxic population even with limited training in EEG interpretation. The hairline montage did not suffice with regard to the differential diagnosis of triphasic waves associated with metabolic encephalopathy and generalized nonconvulsive status epilepticus, but nonetheless detected the vast majority of probable electrographic seizure(s). Our results support the use of EEG monitoring with fewer electrodes for the detection of ictal EEG activity in the postanoxic population. PMID- 27369693 TI - [Are the most recent basal insulins really the most innovative?]. PMID- 27369694 TI - Iohexol plasma clearance in children: validation of multiple formulas and two point sampling times. AB - BACKGROUND: In children, estimated glomerular filtration rate (eGFR) methods are hampered by inaccuracy, hence there is an obvious need for safe, simplified, and accurate measured GFR (mGFR) methods. The aim of this study was to evaluate different formulas and determine the optimal sampling points for calculating mGFR based on iohexol clearance measurements on blood samples drawn at two time points (GFR2p). METHODS: The GFR of 96 children with different stages of chronic kidney disease (CKD) (median age 9.2 years, range 3 months to 17.5 years) was determined using the iohexol plasma clearance, with blood sampling at seven time points within 5 h (GFR7p) as the reference method. Median GFR7p was 65.9 (range 6.3-153) mL/min/1.73 m2. The performance of seven different formulas with early and late normalization to body surface area (BSA) was validated against the reference. RESULTS: The highest percentage (95.8 %) of GFR2p within 10 % of the reference was calculated using the formula of Jodal and Brochner-Mortensen (JBM) from 2009, with sampling at 2 and 5 h. Normalization to BSA before correction of the distribution phase improved the performance of the original Brochner-Mortensen method from 1972; P10 of 92.7 % compared to P10 of 82.3 % with late normalization, and a similar result was obtained with other formulas. CONCLUSIONS: GFR2p performed well across a wide spectrum of GFR levels with the JBM formula. Several other formulas tested performed well provided that early BSA normalization was performed. Blood sampling at 2 and 5 h is recommended for an optimal GFR2p assessment. PMID- 27369695 TI - The role of apelin in the healing of water-immersion and restraint stress-induced gastric damage. AB - The objective of this study was to explore the role of apelin in the healing of gastric lesions induced by stress. Male Wistar rats were exposed to water immersion and restraint stress (WIRS) for 6 h with or without the apelin receptor antagonist F13A. The rats were killed on the 1st, 3rd, 5th or 10th day after the end of stress induction. Apelin and hypoxia-inducible factor-1alpha expression was increased on the 1st day after the end of stress exposure and was decreased daily thereafter. However, F13A retarded the healing of gastric lesions by preventing the improvement of mucosal blood flow, prostaglandin E2 production and vascular endothelial growth factor expression in rats exposed to WIRS. Additionally, F13A increased the gastric 4-hydroxynonenol + malondialdehyde content on the 1st and 3rd days after the end of stress induction but did not affect the change in gastric mucosal nitric oxide levels. In conclusion, apelin may be a regulatory protein involved in the healing mechanism of stress-induced gastric damage. PMID- 27369696 TI - Sustained Use of Patient Portal Features and Improvements in Diabetes Physiological Measures. AB - BACKGROUND: Personal health records (PHRs) have the potential to improve patient self-management for chronic conditions such as diabetes. However, evidence is mixed as to whether there is an association between PHR use and improved health outcomes. OBJECTIVE: The aim of this study was to evaluate the association between sustained use of specific patient portal features (Web-based prescription refill and secure messaging-SM) and physiological measures important for the management of type 2 diabetes. METHODS: Using a retrospective cohort design, including Veterans with diabetes registered for the My Health e Vet patient portal who had not yet used the Web-based refill or SM features and who had at least one physiological measure (HbA1c, low-density lipoprotein (LDL) cholesterol, blood pressure) in 2009-2010 (baseline) that was above guideline recommendations (N=111,686), we assessed portal use between 2010 and 2014. We calculated the odds of achieving control of each measure by 2013 to 2014 (follow up) by years of using each portal feature, adjusting for demographic and clinical characteristics associated with portal use. RESULTS: By 2013 to 2014, 34.13% (38,113/111,686) of the cohort was using Web-based refills, and 15.75% (17,592/111,686) of the cohort was using SM. Users were slightly younger (P<.001), less likely to be eligible for free care based on economic means (P<.001), and more likely to be women (P<.001). In models adjusting for both features, patients with uncontrolled HbA1c at baseline who used SM were significantly more likely than nonusers to achieve glycemic control by follow-up if they used SM for 2 years (odds ratio-OR=1.24, CI: 1.14-1.34) or 3 or more years (OR=1.28, CI: 1.12-1.45). However, there was no significant association between Web-based refill use and glycemic control. Those with uncontrolled blood pressure at baseline who used Web-based refills were significantly more likely than nonusers to achieve control at follow-up with 2 (OR=1.07, CI: 1.01-1.13) or 3 (OR=1.08, CI: 1.02-1.14) more years of Web-based refill use. Both features were significantly associated with improvements in LDL cholesterol levels at follow up. CONCLUSIONS: Although rates of use of the refill function were higher within the population, sustained SM use had a greater impact on HbA1c. Evaluations of patient portals should consider that individual components may have differential effects on health improvements. PMID- 27369698 TI - A new look for an evolving profession. AB - Welcome to your new-look Nursing Management. As you turn each page, you will see the publication has been redesigned to create a fresher, more modern and reader friendly feel, based on what our reader research told us you wanted. PMID- 27369697 TI - Accentuation of optical coherence tomography angiography projection artefacts on hyper-reflective retinal layers. PMID- 27369700 TI - Knowledge gap in domestic abuse care. AB - More than one quarter of nursing staff say they lack confidence in supporting people who face domestic abuse, an RCNi survey reveals. PMID- 27369701 TI - Patients' confidence in nursing increases. AB - Perceptions of nursing care have improved, according to the Care Quality Commission's 2015 adult inpatient survey. PMID- 27369702 TI - Delays persist in discharge process. AB - Soaring numbers of blocked beds continue to disrupt patient care in England - despite figures suggesting the NHS might be starting to recover from a difficult start to the year. PMID- 27369699 TI - Directors of nursing key to success of equality strategies. AB - Senior nurses must help drive the organisational change needed to improve the experience of black and minority ethnic staff in the NHS, says a diversity expert. PMID- 27369705 TI - Mission impossible? AB - Has more ever been asked of nurses? Within the space of 24 hours in May, two documents called on them to lead change and take on extra responsibilities in front line care. PMID- 27369706 TI - Leading Change, Adding Value. AB - Essential facts Leading Change, Adding Value is NHS England's new nursing and midwifery framework. It builds on Compassion in Practice (CiP), which set out the 6Cs. While CiP established the values of nursing and midwifery, the new framework explains how staff can help transform the health and care sectors to meet the aims of NHS England's Five Year Forward View. PMID- 27369708 TI - Diabetes network. AB - Diabetes UK has launched a network of information and support for commissioning and improvement in diabetes care. The network is free to join and offers monthly updates on good practice from around the UK, a forum for sharing ideas and learning, and access to Diabetes UK resources. PMID- 27369707 TI - Carers' wellbeing. AB - NHS England, in partnership with other agencies, has developed a toolkit to address changes to the way health and social care organisations must work together to identify, assess and support carers as well as their families. The toolkit covers new duties required of NHS organisations, brought about by the Care Act 2014, and the Children and Families Act 2014, and includes many examples of best practice. The resource helps promote the development of an integrated approach to supporting carers of all ages, between adult social care services, NHS commissioners and providers and the third sector. PMID- 27369709 TI - Estimating risk. AB - A free mobile phone app has been launched providing nurses and other hospital clinicians with a simple way to identify high-risk surgical patients. The app is a phone version of the Surgical Outcome Risk Tool (SORT), originally developed for online use with computers by researchers from the National Confidential Enquiry into Patient Outcome and Death and the University College London Hospital Surgical Outcomes Research Centre. SORT uses information about patients' health and planned surgical procedures to estimate the risk of death within 30 days of an operation. The percentages are only estimates, taking into account the general risks of the procedures and some information about patients, and should not be confused with patient-specific estimates in individual cases. PMID- 27369710 TI - Promoting innovation. AB - The Foundation of Nursing Studies' Patients First programme, which supports nurse led innovation in practice, is open for applications. The initiative offers help with professional and personal development, including direct support in the workplace; learning and development workshops; help with report writing, publishing and dissemination; and a bursary of up to L5,000. PMID- 27369711 TI - Assessing health apps. AB - A survey commissioned by the National Institute for Health and Care Excellence aims to explore the way nurses and midwives engage with mobile technologies, such as smartphones, tablets and health apps. It is seeking opinions on how these apps should be evaluated, and about online patient feedback. Results will inform NICE's plan to develop a central process for evaluating and endorsing health apps, which will enable patients, healthcare professionals and hospitals to identify the most useful. Nurses or midwives practising in the UK, and involved with direct patient care are welcome to take part in the survey. PMID- 27369713 TI - End of life care. AB - The Care Quality Commission has published a report examining people's experiences of end of life care in England. It highlights examples of good practice but shows that the quality of care for some people is still not good enough. The document states that people receive better care when commissioners and services take an equality-led approach and respond to individuals' needs. It makes recommendations for commissioners, has a good practice case studies document and detailed findings on the ten categories of people studied. PMID- 27369712 TI - Focus on chief executives. AB - According to the King's Fund, there is widespread perception of a 'crisis of leadership' in the NHS, partly illustrated by the difficulties in recruiting and retaining chief executives. The Chief Executive's Tale, a report published by the King's Fund and NHS Partners, draws on the experiences of 12 departed, or departing, chief executives, to highlight the realities of leadership in today's health service. The interviews illustrate positive aspects of the role, as well as challenges that need to be addressed to retain experienced leaders and recruit the next generation. PMID- 27369716 TI - The nursing associate role: have we been here before? AB - What should the nursing workforce of the future look like? It is a question all nurse leaders should ask themselves. PMID- 27369717 TI - Action on antibiotics. AB - It is now acknowledged widely at international level that antimicrobial resistance requires urgent action - and not just in the healthcare sector and pharmaceutical industry, but within farming and among the wider public. PMID- 27369720 TI - Treat students as potential employees. AB - In today's complex, chaotic, and rapidly changing healthcare environment, a newly registered nurse will face many obstacles on the journey into a professional role. PMID- 27369722 TI - Needed: a new model for primary care. AB - Ten years ago a team of nurses took the initiative to run a GP practice in London. What began as a social enterprise project became one of the first nurse led GP practices in the country. A decade on, it is still the only one. Why? PMID- 27369724 TI - Reducing waste in the NHS: an overview of the literature and challenges for the nursing profession. AB - Waste in the NHS is estimated to account for 20% of health expenditure. This article examines the literature on reducing waste, analyses some approaches to waste reduction, and identifies the role that nurses and other health professionals can play in developing a sustainable NHS. For the purposes of the article, and to inform nursing practice, the definition of, and discussion about, waste is broader than that outlined by the Department for Environment, Food and Rural Affairs (Defra) controlled waste regulations, and the Royal College of Nursing classification. It includes clinical waste, waste arising out of clinical practice, service delivery and care, infrastructure, and carbon emissions. PMID- 27369725 TI - Improving the quality of the NHS workforce through values and competency-based selection. AB - Robust selection processes are essential to ensure the best and most appropriate candidates for nursing, midwifery and allied health professional (NMAHP) positions are appointed, and subsequently enhance patient care. This article reports on a study that explored interviewers' and interviewees' experiences of using values and competency-based interview (VCBI) methods for NMAHPs. Results suggest that this resource could have a positive effect on the quality of the NMAHP workforce, and therefore on patient care. This method of selection could be used in other practice areas in health care, and refinement of the resource should focus on supporting interview panels to develop their VCBI skills and experience. PMID- 27369726 TI - Evaluation of the safety and efficacy of same-day discharge following outpatient surgery in a US hospital. AB - In the US, safe and effective same-day discharge of patients, following uncomplicated, ambulatory surgery, also referred to as outpatient surgery, significantly reduces the nursing hours spent caring for patients who do not require hospital admission. Data from the last three decades show that same-day discharge for patients who undergo approved outpatient surgical procedures carries no higher risk of complications than for those who stay for 24-hour observation. This article describes a service development project which evaluated patients' perceived preparedness for same-day discharge. Results suggest that a standardised approach to managing potential complicating factors, such as pain and patients' expectations, can increase the number of successful same-day discharges. The terms outpatient and ambulatory are used interchangeably in the article, and refer to surgical procedures for which inpatient admission is not considered necessary by patients' insurance providers. PMID- 27369727 TI - Staffing issues keep me awake at night. AB - What makes a good nurse leader? A good nurse leader should be credible, visible, approachable and accessible to staff. PMID- 27369728 TI - Depression in transition to becoming a new father. AB - Over the past three decades, there has been a growing awareness about the burden of ill-health experienced by men. PMID- 27369730 TI - Online. AB - Support time recovery workers. This group of staff has not been supported adequately since the last of them was put into post in 2007. PMID- 27369729 TI - Nursing supervision. AB - Supervision is an important resource in mental health nursing, and a clear understanding of the process and practice is essential to improve supervision quality. PMID- 27369732 TI - Addressing violence against older women. AB - Domestic abuse is widespread and indiscriminate, causing health-related concerns and mental health issues in older women. Research suggests their needs are not met by existing services. This article examines physical and mental health issues faced by older women as a result of abusive relationships, and the barriers that exist to seeking help. Healthcare professionals can facilitate therapeutic engagement of older women living with domestic abuse. Refuges and related interventions are limited, but developing a stepped approach, tailored to older women's needs, could help. PMID- 27369733 TI - [Use of botulinum toxin in strabismus]. AB - Botulinum toxin can be a useful tool for treating acute sixth nerve palsy and excessive eye deviations due to unstable Graves' disease, when surgery is not yet possible. The diagnostic injection for estimation of possible postoperative double vision also makes sense. In convergence spasms, periocular botulinum toxin injections can be a therapeutic option. Botulinum toxin is not a first line option in infantile esotropia without binocularity or in adult horizontal strabismus. Side effects include ptosis and vertical deviations. PMID- 27369734 TI - [Intraoperative real-time OCT in macular surgery]. AB - BACKGROUND: Spectral domain optical coherence tomography (SD-OCT) has become a standard diagnostic tool in the surgical management of vitreomacular interface disorders. The high-resolution cross-sectional information obtained from SD-OCT is a perfect complement to vitreoretinal surgery. It provides detailed intraoperative anatomical views that are not possible with a microscope. OBJECTIVE: To investigate the value of intraoperative real-time OCT with respect to improvement of surgical techniques in the management of vitreomacular disorders. METHODS: A review of the current literature was conducted and an analysis of own systematically evaluated data was included to provide a comprehensive overview of potential applications for the clinical use of intraoperative real-time OCT in macular surgery. RESULTS: Intraoperative real time OCT can provide detailed visualization of epiretinal membranes and help to identify whether complete membrane removal has been achieved following surgery. In addition, it can provide qualitative and quantitative information that has previously not been available and assist in surgical decision-making. Intraoperative real-time OCT allows membrane peeling to be performed in selected cases without using retinal dyes, whereas it is not ideal for accurately guiding the surgeon while performing maneuvers. CONCLUSION: Intraoperative real-time OCT provides high-resolution visualization of the effects of surgical maneuvers on the microarchitecture of the retina and surrounding tissues and will fill a gap in the understanding of the pathophysiology and prognostic factors of vitreomacular disorders; however, with currently available systems, accurate intraoperative real-time guidance of surgical maneuvers is hindered by several limiting factors. PMID- 27369737 TI - Effects of a Training Intervention for Enhancing Recovery after Ivor-Lewis Esophagus Surgery: A Randomized Controlled Trial. AB - BACKGROUND AND AIMS: There is a risk of decreased physical function, quality of life and persistent pain after open surgery for esophageal cancer. There are currently no studies that evaluate the effect of any postoperative intervention, including physical exercises, after this type of surgery. The aim of the study was therefore to evaluate the effect of a training intervention after Ivor-Lewis resection of the esophagus. MATERIAL AND METHODS: Patients scheduled for esophagus resection according to Ivor-Lewis were randomized to an intervention group or a control group. The training intervention started at discharge and lasted three months. Before discharge, patients were given three leaflets with exercises to increase range of motion in the affected area and exercises aiming to restore lung function and physical function. All exercises were described in detail and the patients carried out the ones in the first program under supervision. Before surgery and three months after discharge, the patients estimated their level of physical function, level of physical activity, and quality of life. They also underwent spirometry, measurements of range of motion in the rib cage, spine, and shoulders, and three functional tests. Comparisons of differences within and between the groups were made. RESULTS: A total of 43 of 64 randomized patients participated in the follow-up. Postoperatively, the patients in the intervention group had a significantly higher degree of physical function and less deteriorated range of motion in right shoulder flexion and thoracic left lateral flexion. There were no significant differences between the groups in lung function, pain, or quality of life. CONCLUSION: The results of the three-month intervention indicate that specific training can positively affect physical function and range of motion to preoperative values. The intervention was well tolerated, and no side effects were registered. PMID- 27369736 TI - First comprehensive structural and biophysical analysis of MAPK13 inhibitors targeting DFG-in and DFG-out binding modes. AB - BACKGROUND: P38 MAP kinases are centrally involved in mediating extracellular signaling in various diseases. While much attention has previously been focused on the ubiquitously expressed family member MAPK14 (p38alpha), recent studies indicate that family members such as MAPK13 (p38delta) display a more selective cellular and tissue expression and might therefore represent a specific kinase to target in certain diseases. METHODS: To facilitate the design of potent and specific inhibitors, we present here the structural, biophysical, and functional characterization of two new MAPK13-inhibitor complexes, as well as the first comprehensive structural, biophysical, and functional analysis of MAPK13 complexes with four different inhibitor compounds of greatly varying potency. RESULTS: These inhibitors display IC50 values either in the nanomolar range or micromolar range (>800-fold range). The nanomolar inhibitors exhibit much longer ligand-enzyme complex half-lives compared to the micromolar inhibitors as measured by biolayer interferometry. Crystal structures of the MAPK13 inhibitor complexes reveal that the nanomolar inhibitors engage MAPK13 in the DFG-out binding mode, while the micromolar inhibitors are in the DFG-in mode. Detailed structural and computational docking analyses suggest that this difference in binding mode engagement is driven by conformational restraints imposed by the chemical structure of the inhibitors, and may be fortified by an additional hydrogen bond to MAPK13 in the nanomolar inhibitors. CONCLUSIONS: These studies provide a structural basis for understanding the differences in potency exhibited by these inhibitors. GENERAL SIGNIFICANCE: They also provide the groundwork for future studies to improve specificity, potency, pharmacodynamics, and pharmacokinetic properties. PMID- 27369738 TI - A Prospective Analysis on Functional Outcomes Following Extended Latissimus Dorsi Flap Breast Reconstruction. AB - BACKGROUND: To prospectively assess the functional effect of using the extended latissimus dorsi flap in immediate breast reconstructions. MATERIALS AND METHODS: A total of 15 consecutive patients undergoing breast reconstruction with extended latissimus dorsi flap participated. Shoulder range of motion, muscle strength, lateral flexion of the torso, and position of scapula were measured pre operatively and 1, 6, and 12 months post-operatively, in addition to donor-site post-operative complications. RESULTS: At 12 months post-operatively, patients had achieved full range of shoulder movement, when compared to pre-operative values. Lateral flexion of the torso was, however, significantly reduced bilaterally at 1 and 6 months post-operatively (p = 0.001, p = 0.01) and to the not operated side at 12 months (p = 0.01). Muscle strength in flexion-extension internal rotation was significantly (p = 0.01) reduced on the operated side 12 months post-operatively. All but one patient had numbness around the donor-site scar 12 months post-operatively, 33% had slight adhesions but all were pain free. CONCLUSION: Although invariably, patients having extended latissimus dorsi flap may expect to achieve full range of shoulder movement, they should be informed of possible functional consequences and the time and effort it takes to recover. Further research is needed to investigate the potential long-term functional implications that extended latissimus dorsi flap may have as a result of changes in the lateral flexion of the torso and scapula position. PMID- 27369735 TI - Polyphenol compounds and PKC signaling. AB - BACKGROUND: Naturally occurring polyphenols found in food sources provide huge health benefits. Several polyphenolic compounds are implicated in the prevention of disease states, such as cancer. One of the mechanisms by which polyphenols exert their biological actions is by interfering in the protein kinase C (PKC) signaling pathways. PKC belongs to a superfamily of serine-threonine kinase and are primarily involved in phosphorylation of target proteins controlling activation and inhibition of many cellular processes directly or indirectly. SCOPE OF REVIEW: Despite the availability of substantial literature data on polyphenols' regulation of PKC, no comprehensive review article is currently available on this subject. This article reviews PKC-polyphenol interactions and its relevance to various disease states. In particular, salient features of polyphenols, PKC, interactions of naturally occurring polyphenols with PKC, and future perspective of research on this subject are discussed. MAJOR CONCLUSIONS: Some polyphenols exert their antioxidant properties by regulating the transcription of the antioxidant enzyme genes through PKC signaling. Regulation of PKC by polyphenols is isoform dependent. The activation or inhibition of PKC by polyphenols has been found to be dependent on the presence of membrane, Ca(2+) ion, cofactors, cell and tissue types etc. Two polyphenols, curcumin and resveratrol are in clinical trials for the treatment of colon cancer. GENERAL SIGNIFICANCE: The fact that 74% of the cancer drugs are derived from natural sources, naturally occurring polyphenols or its simple analogs with improved bioavailability may have the potential to be cancer drugs in the future. PMID- 27369739 TI - Extralevator with vs nonextralevator abdominoperineal excision for rectal cancer: the RELAPe randomized controlled trial. AB - AIM: A randomized controlled trial was conducted to test the null hypothesis that there is no difference in circumferential resection margin (CRM) between extralevator abdominoperineal excision (ELAPE) and non-ELAPE for rectal cancer. METHOD: This was a multicentre, randomized controlled trial registered as NCT01702116. Patients with rectal cancer involving the external anal sphincter were randomized to ELAPE or non-ELAPE following neoadjuvant chemoradiation. Randomization was performed according to Consolidated Standards of Reporting Trials (CONSORT) guidelines. The primary end-point was CRM (in mm), defined as the shortest distance between the tumour and the cut edge of the specimen. Pathologists and centralized pathology were blinded to the patients' study arm. Interrater reliability (IRR) was assessed using Kendall's coefficient. Intra operative perforation (IOP) was any rectal defect determined at pathology. Complications were classified using the Clavien-Dindo classification. Participating surgeons were retrained and credentialed. A sample size calculation showed that 34 subjects would provide sufficient power to reject the null hypothesis. RESULTS: Thirty-four patients underwent the allocated intervention. Seventeen patients treated with ELAPE were comparable with 17 patients treated with non-ELAPE regarding age, gender, body mass index (BMI), American Society of Anesthesiology (ASA) class and pre-existing comorbidities. CRM depth (7.14 +/- 5.76 mm vs 2.98 +/- 3.28 mm, P = 0.016) and involvement rates (5.8% vs 41.0%, P = 0.04) were significantly increased in patients treated with ELAPE. The IRR for CRM was 0.78. There were no significant differences in IOP (5.8% vs 11.7%, P = 0.77) and complication rates (29% vs 29%, P = 0.97). CONCLUSIONS: ELAPE was associated with statistically improved CRM with no difference in IOP and complication rates compared with non-ELAPE for rectal cancer involving the external anal sphincter. PMID- 27369740 TI - Accuracy of elastography point quantification and steatosis influence on assessing liver fibrosis in patients with chronic hepatitis C. AB - BACKGROUND & AIMS: Elastography point quantification is a novel non-invasive method for the assessment of liver fibrosis by measuring liver stiffness. The aim of this study was to evaluate the accuracy of elastography point quantification for the diagnosis of liver fibrosis and to assess impact of steatosis on liver stiffness measurement, in a cohort of patients with chronic hepatitis C. METHODS: In this single-centre cross-sectional study, 211 consecutive patients with chronic hepatitis C, scheduled for liver biopsy, were examined with the elastography point quantification technology. On the same day, all patients underwent clinical examination, laboratory tests and abdominal ultrasound. RESULTS: The best cut-offs of liver stiffness measurement were 6.16 kPa for the diagnosis of significant fibrosis (>=S3) and 6.79 kPa for advanced fibrosis (>=S4). Areas under the receiver operating characteristic curve were 0.831 (CI: 0.773-0.880) for significant fibrosis, and 0.954 (CI: 0.916-0.978) for advanced fibrosis. Among patients within the same fibrosis stages (S0-S2 and S3-S6; S0-S3 and S4-S6), mean liver stiffness measurement values were similar in patients with steatosis (>=10% at liver biopsy or detected by ultrasound) compared to those without. Discordance between elastography point quantification and histology were affected by the presence of BMI>30 kg/m2 (P=.047, CI: 0.136-0.988 and P=.020, CI: 0.083-0.812 respectively). CONCLUSIONS: In patients with chronic hepatitis C, elastography point quantification is an accurate non-invasive method for the diagnosis of significant and advanced fibrosis. The presence of obesity is a risk factor for misclassification of significant and advanced liver fibrosis. PMID- 27369742 TI - [Not Available]. PMID- 27369744 TI - [Not Available]. PMID- 27369741 TI - Calnexin, an ER stress-induced protein, is a prognostic marker and potential therapeutic target in colorectal cancer. AB - BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer mortality in the Western world and commonly treated with genotoxic chemotherapy. Stress in the endoplasmic reticulum (ER) was implicated to contribute to chemotherapeutic resistance. Hence, ER stress related protein may be of prognostic or therapeutic significance. METHODS: The expression levels of ER stress proteins calnexin, calreticulin, GRP78 and GRP94 were determined in n = 23 Stage II and III colon cancer fresh frozen tumour and matched normal tissue samples. Data were validated in a cohort of n = 11 rectal cancer patients treated with radiochemotherapy in the neoadjuvant setting. The calnexin gene was silenced using siRNA in HCT116 cells. RESULTS: There were no increased levels of ER stress proteins in tumour compared to matched normal tissue samples in Stage II or III CRC. However, increased calnexin protein levels were predictive of poor clinical outcome in the patient cohort. Data were validated in the rectal cancer cohort treated in the neoadjuvant setting. Calnexin gene-silencing significantly reduced cell survival and increased cancer cell susceptibility to 5FU chemotherapy. CONCLUSION: Increased tumour protein levels of calnexin may be of prognostic significance in CRC, and calnexin may represent a potential target for future therapies. PMID- 27369743 TI - [Not Available]. PMID- 27369745 TI - [Not Available]. PMID- 27369746 TI - [Not Available]. PMID- 27369747 TI - [Not Available]. PMID- 27369748 TI - [Not Available]. PMID- 27369749 TI - [Not Available]. PMID- 27369751 TI - [Not Available]. PMID- 27369750 TI - [Not Available]. PMID- 27369752 TI - [Not Available]. PMID- 27369754 TI - [Not Available]. PMID- 27369753 TI - [Not Available]. PMID- 27369755 TI - [Not Available]. PMID- 27369756 TI - [Not Available]. PMID- 27369757 TI - [Not Available]. PMID- 27369758 TI - [Not Available]. PMID- 27369759 TI - [Not Available]. PMID- 27369760 TI - [Not Available]. PMID- 27369761 TI - [Not Available]. PMID- 27369762 TI - [Not Available]. PMID- 27369763 TI - [Not Available]. PMID- 27369764 TI - Novel microsatellite markers for Distylium lepidotum (Hamamelidaceae) endemic to the Ogasawara Islands. AB - BACKGROUND: Distylium lepidotum is a small tree endemic to the Ogasawara Islands located in the northwestern Pacific Ocean. This species is a sole food for an endemic locust, Boninoxya anijimensis. Here, we developed microsatellite markers to investigate genetic diversity and genetic structure and to avoid a genetic disturbance after transplantation to restore the Ogasawara Islands ecosystem. RESULTS: Microsatellite markers with perfect dinucleotide repeats were developed using the next-generation sequencing Illumina MiSeq Desktop Sequencer. Thirty-two primer pairs were characterized in two D. lepidotum populations on Chichijima and Hahajima Islands of the Ogasawara Islands. The number of alleles for the markers ranged from three to 23 per locus in the two populations. Expected heterozygosity per locus in each population ranged from 0.156 to 0.940 and 0.368 to 0.845, respectively. CONCLUSIONS: These microsatellite markers will be useful for future population genetics studies of D. lepidotum and provide a basis for conservation management of the Ogasawara Islands. PMID- 27369765 TI - Evolving the L-lysine high-producing strain of Escherichia coli using a newly developed high-throughput screening method. AB - This study provided a new method which applied a selected L-lysine-inducible promoter for evolving lysine industrial strains of E. coli. According to the intracellular levels of the enhanced green fluorescent protein (EGFP) whose expression was controlled by the promoter, 186 strains were preliminarily selected using fluorescence-activated cell sorting from a 10-million-mutant library generated from a L-lysine high-producing E. coli strain. By subsequent multiple parameter evaluation of the 186 selected strains according to the concentration and the yield of lysine, the productivity per unit of cell in 96 deep-well blocks, two mutants MU-1 and MU-2 were obtained. They produced 136.51 +/- 1.55 and 133.2 9 +/- 1.42 g/L of lysine, respectively, in 5-L jars. Compared with the lysine concentration and the yield of the original strain, those of strain MU-1 improved by 21.00 and 9.05 %, respectively, and those of strain MU-2 improved by 18.14 and 10.41 %, respectively. The mutant selection and evaluation system newly established in our study should be useful for continuous improvement of the current E. coli strains in the lysine industry. PMID- 27369766 TI - Abnormal 8-Hz flicker electroretinograms in carriers of X-linked retinoschisis. AB - PURPOSE: To evaluate rod-isolated, cone-isolated, and combined rod and cone flicker electroretinograms (ERGs) as a possible means to identify electrophysiological abnormalities in carriers of X-linked retinoschisis (XLRS). METHODS: Full-field ERGs were recorded from six carriers of XLRS (aged 34-66 years) and eight normally sighted subjects (aged 27-59 years) under rod-isolated (ERGR), cone-isolated (ERGC), and combined rod and cone (ERGR+C) conditions. ERGs were obtained using a four-primary LED-based ganzfeld photostimulator and standard recording techniques. The four primaries were modulated sinusoidally in phase to achieve combined rod and cone activation (ERGR+C) or in different phases to achieve ERGR and ERGC by means of triple silent substitution. After 30 min of dark adaptation, 8- and 15-Hz ERGR, ERGC, and ERGR+C responses were obtained at a mean luminance level of 24 scot. cd/m(2). Standard ISCEV ERGs were also obtained from each subject. RESULTS: The ISCEV and 15-Hz flicker ERGs were generally within the normal range for the carriers. The 8-Hz ERGR, ERGC, and ERGR+C amplitudes were also generally normal. In contrast, the carriers had ERGR, ERGC, and ERGR+C timing abnormalities, with phase advances beyond the range of normal for the ERGR (four carriers), ERGC (four carriers), and ERGR+C (three carriers). Only one carrier had normal 8-Hz responses under all conditions. CONCLUSIONS: The 8-Hz ERG timing abnormalities in five of six carriers indicate that retinal function is not necessarily normal in carriers of XLRS. The 8-Hz flicker ERG may be useful for studying retinal function in these individuals. PMID- 27369767 TI - Cigarette smoking and the risk of head and neck cancer in the Japanese population: a systematic review and meta-analysis. AB - OBJECTIVE: Although cigarette smoking is a well-established risk factor for head and neck cancer, the impact of smoking on head and neck cancer might vary among geographic areas. To date, however, no systematic review of cigarette smoking and head and neck cancer in the Japanese population has yet appeared. METHODS: We conducted a systematic review of previous epidemiological studies for cigarette smoking and head and neck cancer among Japanese. Evaluation of associations was based on the strength of evidence ('convincing', 'probable', 'possible' or 'insufficient') and the magnitude of association ('strong', 'moderate', 'weak' or 'no association'), together with biological plausibility as previously evaluated by the International Agency for Research on Cancer. A meta-analysis was conducted to obtain summary estimates for the overall magnitude of association. RESULTS: We identified five cohort studies and 12 case-control studies. Four of five cohort studies and 11 of 12 case-control studies showed a strong positive association between cigarette smoking and head and neck cancer. Nine of 12 studies indicated a dose-response relationship between cigarette smoking and the risk of head and neck cancer. Meta-analysis of 12 studies indicated that the summary relative risk for ever smokers relative to never smokers was 2.43 (95% confidence interval: 2.09-2.83). Summary relative risks for current and former smokers relative to never smokers were 2.68 (2.08-3.44) and 1.49 (1.05-2.11), respectively. CONCLUSIONS: Cigarette smoking is a convincing risk factor for head and neck cancer in the Japanese population. PMID- 27369768 TI - Architecture of the caveolar coat complex. AB - Caveolae are specialized membrane domains that are crucial for the correct function of endothelial cells, adipocytes and muscle cells. Caveolins and cavins are both required for caveolae formation, and assemble into a large (80S) caveolar coat complex (80S-CCC). The architecture of the 80S-CCC, however, has not been analyzed. Here, we study the 80S-CCC isolated from mammalian cells using negative stain electron microscopy and 3D cryo-electron tomography. We show that the 80S-CCC is a hollow sphere with a diameter of 50-80 nm, and so has the same size and shape as individual caveolar bulbs. This provides strong evidence that the distinctive membrane shape of caveolae is generated by the shape of the 80S CCC itself. The particle appears to be made up of two layers, an inner coat composed of polygonal units of caveolins that form a polyhedral cage, and an outer filamentous coat composed of cavins. The data suggest that the peripheral cavin coat is aligned along the edges of the inner polyhedral cage, thereby providing a mechanism for the generation of a morphologically stable caveolar coat. PMID- 27369770 TI - [Not Available]. PMID- 27369769 TI - [Not Available]. PMID- 27369771 TI - [Not Available]. PMID- 27369772 TI - [Not Available]. PMID- 27369773 TI - [Not Available]. PMID- 27369774 TI - [Not Available]. PMID- 27369775 TI - [Not Available]. PMID- 27369776 TI - [Not Available]. PMID- 27369777 TI - Effect of ethanol at clinically relevant concentrations on atrial inward rectifier potassium current sensitive to acetylcholine. AB - Alcohol intoxication tends to induce arrhythmias, most often the atrial fibrillation. To elucidate arrhythmogenic mechanisms related to alcohol consumption, the effect of ethanol on main components of the ionic membrane current is investigated step by step. Considering limited knowledge, we aimed to examine the effect of clinically relevant concentrations of ethanol (0.8-80 mM) on acetylcholine-sensitive inward rectifier potassium current I K(Ach). Experiments were performed by the whole-cell patch clamp technique at 23 +/- 1 degrees C on isolated rat and guinea-pig atrial myocytes, and on expressed human Kir3.1/3.4 channels. Ethanol induced changes of I K(Ach) in the whole range of concentrations applied; the effect was not voltage dependent. The constitutively active component of I K(Ach) was significantly increased by ethanol with the maximum effect (an increase by ~100 %) between 8 and 20 mM. The changes were comparable in rat and guinea-pig atrial myocytes and also in expressed human Kir3.1/3.4 channels (i.e., structural correlate of I K(Ach)). In the case of the acetylcholine-induced component of I K(Ach), a dual ethanol effect was apparent with a striking heterogeneity of changes in individual cells. The effect correlated with the current magnitude in control: the current was increased by eth-anol in the cells showing small current in control and vice versa. The average effect peaked at 20 mM ethanol (an increase of the current by ~20 %). Observed changes of action potential duration agreed well with the voltage clamp data. Ethanol significantly affected both components of I K(Ach) even in concentrations corresponding to light alcohol consumption. PMID- 27369779 TI - In vitro effects of platelet-rich gel supernatants on histology and chondrocyte apoptosis scores, hyaluronan release and gene expression of equine cartilage explants challenged with lipopolysaccharide. AB - BACKGROUND: Platelet-rich plasma (PRP) preparations are a common treatment in equine osteoarthritis (OA). However, there are controversies regarding the ideal concentration of platelets and leukocytes in these biological substances necessary to induce an adequate anti-inflammatory and anabolic response in articular cartilage. The aims were to study the influence of leukocyte- and platelet-rich gel (L-PRG) and pure platelet-rich gel (P-PRG) supernatants on the histological changes of cartilage, the degree of chondrocyte apoptosis, the production of hyaluronan (HA) and the gene expression of nuclear factor kappa beta (NFkbeta), matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), collagen type I alpha 1 (COL1A1), collagen type II alpha 1 (COL2A1) and cartilage oligomeric matrix protein (COMP) in normal cartilage explants (CEs) challenged with lipopolysaccharide (LPS). RESULTS: Overall, 25 % L-PRG supernatant (followed in order of importance by, 50 % P-PRG, 25 % P-PRG and 50 % L-PRG) represented the substance with the most important anti-inflammatory and anabolic effect. 25 % P PRG supernatant presented important anabolic effects, but it induced a more severe chondrocyte apoptosis than the other evaluated substances. CONCLUSIONS: 25 % L-PRG supernatant presented the best therapeutic profile. Our results demonstrate that the biological variability of PRP preparations makes their application rather challenging. Additional in vivo research is necessary to know the effect of PRP preparations at different concentrations. PMID- 27369778 TI - Therapeutic Elimination of the Type 1 Interferon Receptor for Treating Psoriatic Skin Inflammation. AB - Phototherapy with UV light is a standard treatment for psoriasis, yet the mechanisms underlying the therapeutic effects are not well understood. Studies in human and mouse keratinocytes and in the skin tissues from human patients and mice showed that UV treatment triggers ubiquitination and downregulation of the type I IFN receptor chain IFNAR1, leading to suppression of IFN signaling and an ensuing decrease in the expression of inflammatory cytokines and chemokines. The severity of imiquimod-induced psoriasiform inflammation was greatly exacerbated in skin of mice deficient in IFNAR1 ubiquitination (Ifnar1(SA)). Furthermore, these mice did not benefit from UV phototherapy. Pharmacologic induction of IFNAR1 ubiquitination and degradation by an antiprotozoal agent halofuginone also relieved psoriasiform inflammation in wild-type but not in Ifnar1(SA) mice. These data identify downregulation of IFNAR1 by UV as a major mechanism of the UV therapeutic effects against the psoriatic inflammation and provide a proof of principle for future development of agents capable of inducing IFNAR1 ubiquitination and downregulation for the treatment of psoriasis. PMID- 27369782 TI - [Not Available]. PMID- 27369781 TI - [Not Available]. PMID- 27369783 TI - [Not Available]. PMID- 27369780 TI - Structure/function correlations over binuclear non-heme iron active sites. AB - Binuclear non-heme iron enzymes activate O2 to perform diverse chemistries. Three different structural mechanisms of O2 binding to a coupled binuclear iron site have been identified utilizing variable-temperature, variable-field magnetic circular dichroism spectroscopy (VTVH MCD). For the MU-OH-bridged Fe(II)2 site in hemerythrin, O2 binds terminally to a five-coordinate Fe(II) center as hydroperoxide with the proton deriving from the MU-OH bridge and the second electron transferring through the resulting MU-oxo superexchange pathway from the second coordinatively saturated Fe(II) center in a proton-coupled electron transfer process. For carboxylate-only-bridged Fe(II)2 sites, O2 binding as a bridged peroxide requires both Fe(II) centers to be coordinatively unsaturated and has good frontier orbital overlap with the two orthogonal O2 pi* orbitals to form peroxo-bridged Fe(III)2 intermediates. Alternatively, carboxylate-only bridged Fe(II)2 sites with only a single open coordination position on an Fe(II) enable the one-electron formation of Fe(III)-O2 (-) or Fe(III)-NO(-) species. Finally, for the peroxo-bridged Fe(III)2 intermediates, further activation is necessary for their reactivities in one-electron reduction and electrophilic aromatic substitution, and a strategy consistent with existing spectral data is discussed. PMID- 27369785 TI - [Not Available]. PMID- 27369786 TI - [Not Available]. PMID- 27369784 TI - [Not Available]. PMID- 27369787 TI - [Not Available]. PMID- 27369788 TI - [Not Available]. PMID- 27369789 TI - [Not Available]. PMID- 27369790 TI - [Not Available]. PMID- 27369792 TI - [Not Available]. PMID- 27369791 TI - [Not Available]. PMID- 27369793 TI - [Not Available]. PMID- 27369795 TI - [Not Available]. PMID- 27369794 TI - [Not Available]. PMID- 27369796 TI - [Not Available]. PMID- 27369797 TI - [Not Available]. PMID- 27369799 TI - [Not Available]. PMID- 27369798 TI - [Not Available]. PMID- 27369800 TI - [Not Available]. PMID- 27369801 TI - [Not Available]. PMID- 27369802 TI - [Not Available]. PMID- 27369804 TI - Novel 3-Dimensional Image Fusion Software for Live Guidance of Percutaneous Pulmonary Valve Implantation. PMID- 27369803 TI - Relationship of Annular Sizing Using Multidetector Computed Tomographic Imaging and Clinical Outcomes After Self-Expanding CoreValve Transcatheter Aortic Valve Replacement. AB - BACKGROUND: Multidetector computed tomography is useful for determining the appropriate transcatheter heart valve (THV) size in patients with severe aortic stenosis who are suboptimal surgical candidates. The relationship between adherence to the recommended CoreValve sizing algorithm and clinical outcomes is not known. METHODS AND RESULTS: We evaluated 1023 patients with severe aortic stenosis deemed high or extreme risk for surgery treated with the CoreValve THV. All patients underwent preprocedural multidetector computed tomography, and the scans were reviewed at a central analysis center using standardized software. Compliance to a recommended sizing algorithm was used to identify patients with below-range, in-range, and above-range THV sizing. A device annular sizing ratio (DAR) was also calculated based on the native annulus perimeter and perimeter of the selected THV. Clinical end points included the presence of paravalvular aortic regurgitation evaluated by an independent echocardiographic laboratory. Adherence to the sizing algorithm was highest with a 31-mm THV (92.6%) and lowest with the 23-mm THV (38.5%). Below-range sizing was associated with a higher rate of moderate or severe paravalvular aortic regurgitation (15.3%) than in-range (6.5%) or above-range (10.0%; P<0.001) sizing. Higher DARs were associated with lower rates of moderate or severe paravalvular aortic regurgitation: DAR <=10%, 17.6%; DAR 10% to 15%, 9.9%; DAR 15% to 20%, 6.3%; and DAR >20%, 4.9%; P<0.001. There was no increase in clinical events associated with higher DARs. CONCLUSIONS: Adherence to a sizing algorithm guided by multidetector computed tomography resulted in lower rates of paravalvular aortic regurgitation after self-expanding transcatheter valve replacement without an increase in complications. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01240902. PMID- 27369805 TI - What's in a Name? Roles of RFamide-Related Peptides Beyond Gonadotrophin Inhibition. AB - RFamide-related peptides (RFRPs) have been heavily implicated in the control of reproductive function subsequent to their discovery more than 16 years ago. However, recent studies using genetic and pharmacological tools have challenged their importance in regulating the hypothalamic-pituitary-gonadal axis. It is generally accepted that RFRPs act as part of a wider RFamide system, which involves two receptors, called the neuropeptide FF receptors (NPFFR1 and R2), and includes the closely-related neuropeptide NPFF. NPFF has been studied ever since the 1980s and many of the functions of NPFF are also shared by RFRPs. The current review questions whether these functions of NPFF are indeed specific to just NPFF alone and presents evidence from both neuroendocrine and pharmacological perspectives. Furthermore, recently emerging new functions of RFRPs are discussed with the overall goal of clarifying the functions of RFRPs beyond the hypothalamic-pituitary-gonadal axis. PMID- 27369806 TI - Utilization of metabonomics to identify serum biomarkers in murine H22 hepatocarcinoma and deduce antitumor mechanism of Rhizoma Paridis saponins. AB - Murine H22 hepatocarcinoma model is so popular to be used for the preclinical anticancer candidate's evaluation. However, the metabolic biomarkers of this model were not identified. Meanwhile, Rhizoma Paridis saponins (RPS) as natural products have been found to show strong antitumor activity, while its anti-cancer mechanism is not clear. To search for potential metabolite biomarkers of this model, serum metabonomics approach was applied to detect the variation of metabolite biomarkers and the related metabolism genes and signaling pathway were used to deduce the antitumor mechanisms of RPS. As a result, ten serum metabolites were identified in twenty-four mice including healthy mice, non treated cancer mice, RPS-treated cancer mice and RPS-treated healthy mice. RPS significantly decreased tumor weight correlates to down-regulating lactate, acetate, N-acetyl amino acid and glutamine signals (p < 0.05), which were marked metabolites screened according to the very important person (VIP), loading plot and receiver operating characteristic curve (ROC) tests. For the analysis of metabolic enzyme related genes, RPS reversed the aerobic glycolysis through activating tumor suppressor p53 and PTEN, and suppressed FASN to inhibit lipogenesis. What's more, RPS repressed Myc and GLS expression and decreased glutamine level. The regulating PI3K/Akt/mTOR and HIF-1alpha/Myc/Ras networks also participated in these metabolic changes. Taken together, RPS suppressed ATP product made the tumor growth slow, which indicated a good anti-cancer effect and new angle for understanding the mechanism of RPS. In conclusion, this study demonstrated that the utility of (1)H NMR metabolic profiles taken together with tumor weight and viscera index was a promising screening tool for evaluating the antitumor effect of candidates. In addition, RPS was a potent anticancer agent through inhibiting cancer cellular metabolism to suppress proliferation in hepatoma H22 tumor murine, which promoted the application of RPS in the future. PMID- 27369807 TI - Evaluations of thyme extract effects in human normal bronchial and tracheal epithelial cell lines and in human lung cancer cell line. AB - Thyme (Thymus vulgaris) is used traditionally to prepare herbal remedies possessing expectorant, mucolytic, antitussive and antispasmodic properties. The aim of the present study was to investigate the effects of a standardized hydroalcoholic extract of thyme on primary human airway (bronchial/tracheal) epithelial cell lines in a model of lung inflammation induced by LPS. In addition, the effects of thyme extract on human lung cancer cell line (H460) were analysed. Thyme extract showed significant anti-inflammatory properties by reducing the NF-kappaB p65 and NF-kappaB p52 transcription factors protein levels followed by the decrease of pro-inflammatory cytokines (IL-1 beta and IL-8), and Muc5ac secretion in human normal bronchial and tracheal epithelial cells. Moreover, the extract showed cytotoxic effects on H460 cancer cells, modulated the release of IL-1 beta, IL-8 and down-regulated NF-kappaB p65 and NF-kappaB p52 proteins. Taken together, these results substantiated the traditional uses of thyme in the treatment of respiratory diseases. Thyme extract might be an effective treatment of chronic diseases based on inflammatory processes when hypersecretion of mucus overwhelms the ciliary clearance and obstructs airways, causing morbidity and mortality. Moreover thyme extract, evaluated in H460 lung cancer cell line, demonstrated to induce cell cytotoxicity in addition to reduce inflammatory cell signals. PMID- 27369808 TI - Lipidomics study of plasma phospholipid metabolism in early type 2 diabetes rats with ancient prescription Huang-Qi-San intervention by UPLC/Q-TOF-MS and correlation coefficient. AB - Potential impact of lipid research has been increasingly realized both in disease treatment and prevention. An effective metabolomics approach based on ultra performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) along with multivariate statistic analysis has been applied for investigating the dynamic change of plasma phospholipids compositions in early type 2 diabetic rats after the treatment of an ancient prescription of Chinese Medicine Huang-Qi-San. The exported UPLC/Q-TOF-MS data of plasma samples were subjected to SIMCA-P and processed by bioMark, mixOmics, Rcomdr packages with R software. A clear score plots of plasma sample groups, including normal control group (NC), model group (MC), positive medicine control group (Flu) and Huang-Qi San group (HQS), were achieved by principal-components analysis (PCA), partial least-squares discriminant analysis (PLS-DA) and orthogonal partial least-squares discriminant analysis (OPLS-DA). Biomarkers were screened out using student T test, principal component regression (PCR), partial least-squares regression (PLS) and important variable method (variable influence on projection, VIP). Structures of metabolites were identified and metabolic pathways were deduced by correlation coefficient. The relationship between compounds was explained by the correlation coefficient diagram, and the metabolic differences between similar compounds were illustrated. Based on KEGG database, the biological significances of identified biomarkers were described. The correlation coefficient was firstly applied to identify the structure and deduce the metabolic pathways of phospholipids metabolites, and the study provided a new methodological cue for further understanding the molecular mechanisms of metabolites in the process of regulating Huang-Qi-San for treating early type 2 diabetes. PMID- 27369810 TI - Effects of perinatal undernutrition on the circumvallate papilla of developing Wistar rats. AB - During the gestation and the lactating periods the gustatory papillae contain taste buds that respond to different flavors and aversive stimuli. The current study analyzed the effects of pre-and neonatal undernutrition on the circumvallate papillae of rats at 12, 20, and 30days of age. Early undernourishment occurred from gestational days G6 to G19 when dams received low percentages of food followed by a balanced diet from G20-21. After birth pups were underfed by rotating two lactating dams every 12h; in one of them, the nipples were tied. The pups were weaned at 25days of age, and then given an ad libitum diet. Under anesthesia the tongues were removed and stained with the hematoxylin-eosin (H-E) procedure. The results indicated that young underfed rats had significantly body weight reductions. The tongue measurements in underfed rats showed reduced total area and length of the anterior portion, but there were negligible effects on the posterior portion. The circumvallate papillae in underfed rats was significantly reduced in major length, major diameter, and total and upper areas, but unaffected in the lateral wall trench region. The taste bud areas and minor diameter were unaffected by undernutrition, but there were significant reductions in the total number of visible taste buds and the major diameter, delayed opening of taste bud pores, and an increased number of closed pores were also observed. These alterations by undernutrition reflect the vulnerability of structures in the gustatory oral cavity and suggest a possible interference with the receptors activation, and transduction and perhaps with the taste encoding of signals to generate the gustatory sensory and hedonic responses. PMID- 27369809 TI - Alcohol-Focused Behavioral Couple Therapy. AB - Alcohol Behavioral Couple Therapy (ABCT) has emerged over the last 30 years as a highly efficacious treatment for those with alcohol use disorders. This review highlights the historical and conceptual underpinnings of ABCT, as well as the specific treatment elements and structure. Proposed active ingredients, moderators, and mediators of treatment outcome are discussed. Efficacy is evaluated for reductions in identified patient drinking, improved relationship functioning, and reductions in intimate partner violence. Adaptations of ABCT for substances other than alcohol are described. Other adaptations, including brief interventions, interventions addressing PTSD and TBI along with alcohol use, and interventions deliverable via technology platforms are described. Additional cost benefit and cost-effectiveness findings supporting the economic value of ABCT are noted. Future directions for research in this area include possible adaptations for female identified patients, nontraditional couples, LGBT partners and dyads involving nonintimate partner relationships. The development of more flexible models and enhanced dissemination strategies may improve clinical uptake and utility as well as increasing the feasibility of this treatment for integrated healthcare settings. PMID- 27369811 TI - Points to consider for a validation study of iPS cell-derived cardiomyocytes using a multi-electrode array system. AB - Human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) provide a novel assay system to assess cardiac safety in drug development to overcome a problem of species difference in non-clinical testing during drug development. Using the multi-electrode array (MEA) platform, electrophysiological activities of iPS-CMs can be recorded easily to assess QT prolongation and proarrhythmic potential of drug candidates. Here we have established a standardized protocol to evaluate the possibility of iPS-CMs, and shared the protocol with an international consortium. To obtain reproducible and reliable experimental data from these cells, we determined the optimal experimental conditions, such as cell density, MEA coating, culture conditions, high-pass filter frequency, definition of early afterdepolarization or triggered activity, and calibration compounds. Based on the protocol, our validation study using 60 compounds is in progress. Thus, MEA-based experiments using iPS-CMs would be a standard testing method to evaluate QT prolongation and proarrhythmic potentials. PMID- 27369812 TI - Magnetic resonance imaging and computed tomography for diagnosing semicircular canal dehiscence. AB - OBJECTIVES: We investigated the semicircular canal (SC) dehiscence using temporal computed tomography (CT) and magnetic resonance (MR) imaging. METHODS: We retrospectively reviewed 114 (228 ears) consecutive MR images and CT scans of the temporal bones for dehiscence of the SCs. In the 1.5 Tesla (T) MR imaging, T1 and T2-weighted images were obtained. Dehiscence of the SCs was defined by absence of high attenuation bone coverage on the CT scans, and absence of low-signal bone margins on the MR images. RESULTS: Superior SC dehiscence was detected in 4 (1.8%) ears using CT scans and 5 (2.2%) ears using MR imaging. Posterior SC dehiscence was detected in 4 (1.8%) ears using CT scans and 4 (1.8%) ears using MR imaging. In the non-dehiscent cases, there was hypointense bone coverage between the canal and the cerebrospinal fluid (CSF). However, in the cases of semicircular canal dehiscence, hypointense bone tissue did not appear between the canal and the CSF in the MR imaging. CONCLUSION: If there is clinical doubt about the presence of SC dehiscence, we recommend that MR imaging be conducted first. When dehiscence is not seen in the MR, a CT examination should be performed. MR imaging is preferred primarily, because it does not contain ionizing radiation. PMID- 27369813 TI - Empiric systemic antibiotics for hospitalized patients with severe odontogenic infections. AB - INTRODUCTION: Odontogenic infections may lead to severe head and neck infections with potentially great health risk. Age, location of purulent affected sites and beta-lactam allergy are some mentionable factors regarding patients' in-hospital stay and course of disease. Are there new challenges regarding bacteria' antibiotic resistance for empiric treatment and what influences do they have on patients' clinical course? METHODS: We analyzed in a 4-year retrospective study the medical records of 294 in-hospital patients with severe odontogenic infections. On a routine base bacteria were identified and susceptibility testing was performed. Length of stay in-hospital was evaluated regarding patients' age, beta-lactam allergy profile, affected sites and bacteria susceptibility to empiric antibiotics. RESULTS: Length of stay in-hospital was detected to be associated with affected space and penicillin allergy as well (p < 0.05). Isolates presented large amounts of aerobic gram-positive bacteria (64.2%), followed by facultative anaerobic bacteria (gram+/15.8%, gram-/12.7%). Tested ampicillin in combination with sulbactam (or without) and cephalosporins displayed high susceptibility rates, revealing distinguished results regarding clindamycin (p < 0.05). Co-trimoxazol and moxifloxacin showed high overall susceptibility rates (MOX: 94.7%, COTRIM: 92.6%). DISCUSSION: This study demonstrates ampicillin/sulbactam in addition to surgical intervention is a good standard in treatment of severe odontogenic neck infections. Cephalosporins seem to be a considerable option as well. If beta-lactam allergy is diagnosed co trimoxazol and moxifloxacin represent relevant alternatives. CONCLUSION: Age, allergic profile and bacteria' resistance patterns for empiric antibiotics have an influence on patients in-hospital stay. Ampicillin/sulbactam proves itself to be good for empiric antibiosis in severe odontogenic infections. Furthermore cephalosporins could be considered as another option in treatment. However moxifloxacin and co-trimoxazol deserves further investigation as empiric antibiosis in odontogenic infections if beta-lactam allergy is diagnosed. PMID- 27369814 TI - The influence of climate on age at menarche: Augmented with the influence of ancestry. AB - Samples representative of South Korea, Indonesia, and Peninsular Malaysia were analyzed and the influence of climate on age at menarche was investigated. The sample size was 24,651 for Korea (birth years 1941-1992), for Indonesia 8331 (birth years 1944-1988) plus 20,519 (birth years 1978-1997), and 2842 for Peninsular Malaysia (birth years 1927-1968). Respondents recalled their age at menarche. The mean age at menarche was calculated for each birth year by country, and for Malaysia, additionally by ancestry. It has been found that mean ages at menarche for the early birth years were much younger in Indonesia than in Korea despite similar levels of socioeconomic conditions (proxied by GDP per capita). For example, for the birth year 1944, the mean age at menarche was 14.45 years for Indonesia and 16.19 years for Korea-a difference of 1.74 years. It was necessary to double the Korean GDP per capita to make the Korean mean age at menarche the same as the Indonesian one. Chinese and Malay women in Peninsular Malaysia were further analyzed, and the results provided indirect evidence that the difference between Korea and Indonesia was not due to ancestry differences. Results in multivariate settings provided consistent results. It has been concluded that climate exerts a significant influence on age at menarche because the relatively easy availability of food in the tropics increases energy intake while the absence of cold weather decreases energy expenditure on maintenance and activity. PMID- 27369816 TI - Renal Branch Artery Stenosis: A Diagnostic Challenge? A Case Report With Review of the Literature. AB - Renovascular hypertension is a common cause of pediatric hypertension. In the fraction of cases that are unrelated to syndromes such as neurofibromatosis, patients with a solitary stenosis on a branch of the renal artery are common and can be diagnostically challenging. Imaging techniques that perform well in the diagnosis of main renal artery stenosis may fall short when it comes to branch artery stenosis. We report 2 cases that illustrate these difficulties and show that a branch artery stenosis may be overlooked even by the gold standard method, renal angiography. PMID- 27369817 TI - Urologic Considerations in the Separation of Thoracoomphalopagus Conjoined Twins. AB - Conjoined twins are seen in approximately 1/500,000 live births, and therefore surgical management of urologic anomalies in conjoined twins has not been extensively reported. Various degrees of sharing of the urinary tracts and genitalia can be seen in different types of conjoined twins. Detailed preoperative imaging, including magnetic resonance imaging, computed tomography, and voiding cystourethrogram, is essential to define the anatomy and planning of a successful separation. We describe the urologic presentation, evaluation, and treatment of thoracoomphalopagus conjoined twins. PMID- 27369815 TI - Nucleotide homeostasis and purinergic nociceptive signaling in rat meninges in migraine-like conditions. AB - Extracellular ATP is suspected to contribute to migraine pain but regulatory mechanisms controlling pro-nociceptive purinergic mechanisms in the meninges remain unknown. We studied the peculiarities of metabolic and signaling pathways of ATP and its downstream metabolites in rat meninges and in cultured trigeminal cells exposed to the migraine mediator calcitonin gene-related peptide (CGRP). Under resting conditions, meningeal ATP and ADP remained at low nanomolar levels, whereas extracellular AMP and adenosine concentrations were one-two orders higher. CGRP increased ATP and ADP levels in meninges and trigeminal cultures and reduced adenosine concentration in trigeminal cells. Degradation rates for exogenous nucleotides remained similar in control and CGRP-treated meninges, indicating that CGRP triggers nucleotide release without affecting nucleotide inactivating pathways. Lead nitrate-based enzyme histochemistry of whole mount meninges revealed the presence of high ATPase, ADPase, and AMPase activities, primarily localized in the medial meningeal artery. ATP and ADP induced large intracellular Ca(2+) transients both in neurons and in glial cells whereas AMP and adenosine were ineffective. In trigeminal glia, ATP partially operated via P2X7 receptors. ATP, but not other nucleotides, activated nociceptive spikes in meningeal trigeminal nerve fibers providing a rationale for high degradation rate of pro-nociceptive ATP. Pro-nociceptive effect of ATP in meningeal nerves was reproduced by alpha,beta-meATP operating via P2X3 receptors. Collectively, extracellular ATP, which level is controlled by CGRP, can persistently activate trigeminal nerves in meninges which considered as the origin site of migraine headache. These data are consistent with the purinergic hypothesis of migraine pain and suggest new targets against trigeminal pain. PMID- 27369819 TI - Reply by the Authors. PMID- 27369818 TI - Surgical Management of Hair-coil Penile Injury: Anatomical Insights and Grading System. AB - OBJECTIVE: To report our experience in the surgical management of a group of patients with varying degrees of hair-coil penile injury, while applying a more detailed grading scale for the severity of injury. PATIENTS AND METHODS: The study included 16 boys with hair-coil penile injury who were managed during the period 2010 through 2016. In the acute state, the constricting hair coil was removed under general anesthesia. The repair was planned 6 months later after the acute injury. In 1 case presenting with severe form (near total glanular amputation), the glans was resutured to the penile shaft immediately after removal of the hair coil; the urethroplasty was performed six months later. RESULTS: The patients' age ranged from 2 to 17 years (mean 4.8 years). The urethroplasty was always covered by a protective layer, which was derived from the ventral dartos fascia in all but 1 case. In the latter, we used a tunica vaginalis flap for covering the urethroplasty. A successful outcome (regarding both urethral reconstruction and cosmesis) was achieved in all cases. CONCLUSION: Hair-coil penile injury is an uncommon condition with insidious course. Unawareness of such condition can lead to progression to serious complications. Delayed and staged surgical repair is associated with successful outcome. PMID- 27369820 TI - [Not Available]. PMID- 27369821 TI - [Not Available]. PMID- 27369822 TI - [Not Available]. PMID- 27369823 TI - [Not Available]. PMID- 27369824 TI - [Not Available]. PMID- 27369826 TI - [Not Available]. PMID- 27369825 TI - [Not Available]. PMID- 27369828 TI - [Not Available]. PMID- 27369827 TI - [Not Available]. PMID- 27369829 TI - [Not Available]. PMID- 27369830 TI - [Not Available]. PMID- 27369832 TI - [Not Available]. PMID- 27369831 TI - [Not Available]. PMID- 27369833 TI - [Not Available]. PMID- 27369834 TI - [Not Available]. PMID- 27369836 TI - [Not Available]. PMID- 27369835 TI - [Not Available]. PMID- 27369837 TI - [Not Available]. PMID- 27369838 TI - [Not Available]. PMID- 27369839 TI - [Not Available]. PMID- 27369840 TI - Preservation of nostril morphology in nasal base reduction. AB - BACKGROUND: Asian patients often desire reduction of the base and alar lobules of the Asian mesorrhine nose. Sill excision is commonly used, but may result in an angular or notched nostril rim. METHODS: We developed an internal method of alar base reduction involving triangle flaps for sill resection. This method avoids alar rim notching and teardrop deformity. Cinching sutures and double-layer closure avoid tension on the wound. We categorized the results in 50 patients (4 men, 46 women) who underwent surgery between November 2012 and August 2015 and who could be followed up for more than 3 months. The mean age of the subjects was 26.3 years and the mean follow-up period was 8.9 months. RESULTS: Forty patients underwent base reduction with the internal method, while ten with alar flare were treated with additional external resection. The mean reduction of the nostril sill width was 4.8 mm for both methods. In the subjects receiving flare resection, the mean reduction of the lateral alar width was 4.4 mm. There was no notching at the suture site. Complications included a short scar running obliquely under the sill in 13 patients and a trap door deformity in one patient. CONCLUSIONS: Nasal base reduction is widely performed, but subject to outcomes with abnormal nostril contour. We used triangle flaps to narrow the sill, and cinching sutures to prevent tension on the wound. Our methods prevent nostril notching and/or teardrop deformity. Scarring can occur, but can be reduced using cinching sutures for wound relaxation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 27369841 TI - A New Technique for Correction of Tethered and Depressed Scars: Layered Dermal Support. AB - BACKGROUND: Many methods have been used for correcting tethered and depressed scars, but most of these methods have had unsatisfying results and ended up with recurrence. The aim of this study is to present a new surgical technique that overcomes these problems. MATERIALS AND METHODS: Twenty-two depressed scars were corrected using the layered dermal support technique. With this technique, the depressed part of the scar is deepithelialized and used in a layered fashion to support the skin flaps. RESULTS: All of the patients were evaluated 1 year postoperatively. There was no recurrence of tethering or depression. CONCLUSION: The layered dermal support technique is a relatively quick procedure that uses only basic plastic surgery principles. It offers a good solution for the correction of tethered and depressed scars without recurrence. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 27369842 TI - Habitat preference and flowering-time variation contribute to reproductive isolation between diploid and autotetraploid Anacamptis pyramidalis. AB - Tetraploid lineages are typically reproductively isolated from their diploid ancestors by post-zygotic isolation via triploid sterility. Nevertheless, polyploids often also exhibit ecological divergence that could contribute to reproductive isolation from diploid ancestors. In this study, we disentangled the contribution of different forms of reproductive isolation between sympatric diploid and autotetraploid individuals of the food-deceptive orchid Anacamptis pyramidalis by quantifying the strength of seven reproductive barriers: three prepollination, one post-pollination prezygotic and three post-zygotic. The overall reproductive isolation between the two cytotypes was found very high, with a preponderant contribution of two prepollination barriers, that is phenological and microhabitat differences. Although the contribution of post zygotic isolation (triploid sterility) is confirmed in our study, these results highlight that prepollination isolation, not necessarily involving pollinator preference, can represent a strong component of reproductive isolation between different cytotypes. Thus, in the context of polyploidy as quantum speciation, that generates reproductive isolation via triploid sterility, ecological divergence can strengthen the reproductive isolation between cytotypes, reducing the waste of gametes in low fitness interploidy crosses and thus favouring the initial establishment of the polyploid lineage. Under this light, speciation by polyploidy involves ecological processes and should not be strictly considered as a nonecological form of speciation. PMID- 27369843 TI - Impact of exercise-based cardiac rehabilitation on long-term clinical outcomes in patients with left main coronary artery stenosis. AB - BACKGROUND: Cardiac rehabilitation may reduce cardiovascular mortality and morbidity rates in patients with coronary artery disease. The specific relationship between cardiac rehabilitation participation and left main coronary artery stenosis is unknown. DESIGN: Prospective registry analysis. METHODS: Data from a registry of 3120 patients with left main coronary artery stenosis, collected between 1995 and 2010, were analyzed. A total of 596 patients (19.6%) had participated in a cardiac rehabilitation program. RESULTS: The crude seven year mortality, cardiovascular mortality, target-vessel revascularization and myocardial infarction rates were significantly lower in the cardiac rehabilitation than in the non-rehabilitation group, and the incidence of stroke tended to be lower in the cardiac rehabilitation group. Multivariate analysis showed that cardiac rehabilitation was associated with significantly lower risks of mortality (hazard ratio (HR), 0.70; 95% confidence interval (CI), 0.49-1.00; p = 0.05) and cardiovascular mortality (HR, 0.69; 95% CI, 0.48-0.97; p = 0.03). However, the adjusted HR of myocardial infarction, target-vessel revascularization and stroke did not differ significantly. Propensity score matched analysis of 507 pairs showed that cardiac rehabilitation was associated with significant decreases in mortality (HR, 0.62; 95% CI, 0.43-0.89; p = 0.009) and cardiovascular mortality (HR, 0.54; 95% CI, 0.36-0.80; p = 0.002) but had no beneficial effects on myocardial infarction, target-vessel revascularization or stroke. CONCLUSIONS: Exercise-based cardiac rehabilitation participation was associated with significant decreases in mortality. Our findings show that cardiac rehabilitation programs should be implemented in standard management for patients with left main coronary artery stenosis. PMID- 27369844 TI - The Emerging Neuroscience of Third-Party Punishment. AB - Although it is far too early to say that cognitive neuroscience will have any direct impact on how we sentence criminals, patterns are nevertheless emerging that suggest a neural framework for punishment that could one day have important legal and social consequences. PMID- 27369845 TI - Peak systolic velocity thresholds of cavernosal penile arteries in patients with and without risk factors for arterial erectile deficiency. AB - To simultaneously assess the peak systolic velocity (PSV) and the end-diastolic velocity (EDV) at dynamic duplex examination of the cavernosal penile arteries, and penile rigidity in subjects with satisfactory erectile function with and without risk factors for arterial erectile deficiency (ED). This multicenter prospective study examined two populations having satisfactory sexual function with dynamic duplex examination of the cavernosal arteries; one population had risk factors for arterial ED (65 patients, Group 1) and the other (60 patients, Group 2) had no risk factors. Penile rigidity was assessed using the Schramek grading system score (SGSS). The PSV, the EDV, and the SGSS values of Group 1 and of Group 2 were measured and compared using analysis of variance. The EDV and PSV data presented in this abstract are the arithmetical means of the data of the left and right cavernosal arteries. The Group 1 patients showed a mean +/- standard deviation PSV of 26.4 +/- 13.2 cm/sec and the Group 2 patients showed a PSV of 44.7 +/- 9.6 cm/sec (p = 0.002). The EDV of Group 1 was -15.6 +/- 16.1 cm/sec and the EDV of Group 2 was -14.9 +/- 13.7 cm/sec (p = 0.329). The SGSS in Group 1 was 3.2 +/- 0.3 and the SGSS in Group 2 was 4.8 +/- 0.2 (p = 0.008). Intra- and inter-operator variability were not statistically significant. The PSVs and the SGSSs of patients with risk factors for ED and satisfactory erectile function were subnormal and significantly lower than the PSVs and the SGSSs of patients without risk factors. It has been hypothesized that compensatory mechanisms, probably of psychological origin, might allow satisfactory erectile response, even in the presence of a subnormal PSV. PMID- 27369846 TI - Pericardial fat volume is related to atherosclerotic plaque burden rather than to lesion severity. AB - Aims: We sought to explore the relationship between pericardial fat volume (PFV) and both coronary atherosclerosis (CA) extent and severity using coronary artery calcium score (CAC), computed tomography coronary angiography (CTCA), and invasive coronary angiography in patients at high to intermediate likelihood of coronary artery disease (CAD). Methods and Results: Patients clinically referred to invasive angiography who underwent CTCA and CAC within 1 month before the procedure comprised the study population. PFV, CAC, atherosclerotic burden indexes [segment involvement score (SIS); segment stenosis score; three-vessel plaque; and any left main plaque], and the invasive angiography-derived CAD index were evaluated independently. A total of 75 patients were included in the study. PFV did not differ between patients with or without obstructive (stenosis >70%) CAD defined by invasive angiography (86.4 +/- 31.7 vs. 77.1 +/- 42.8 cm3, P = 0.34), although patients with obstructive CAD had significantly higher CAC scores [636.0 (IQR 229.5-1101.0) vs. 206.0 (IQR 0.0-675), P < 0.0001] than patients without obstructive CAD. Patients with extensive CA (SIS > 5) had significantly larger PFV (89.9 +/- 33.9 vs. 58.7 +/- 33.2 cm3, P = 0.003) than patients with non-extensive CA. Significant correlations were found between PFV and CAC (r = 0.49, P < 0.0001), and SIS (r = 0.46, P < 0.0001), whereas very weak correlations were observed between PFV and the CAD index (r = 0.27, P = 0.02), and between PFV and the body mass index (r = 0.33, P = 0.004). Conclusion: The main finding of the present study was the identification of PFV as more closely related to atherosclerotic plaque burden rather than to lesion severity in patients referred to invasive coronary angiography. PMID- 27369847 TI - Primary mitral valve sarcoma: multimodality imaging and therapy. PMID- 27369848 TI - Aortic dissection mimicking a massive pulmonary embolism. PMID- 27369849 TI - Percutaneous valve-in-homograft for management of a failed homograft. PMID- 27369850 TI - Congenital aorta to right main pulmonary artery arteriovenous malformation. PMID- 27369851 TI - Stability of left ventricular longitudinal and circumferential deformation over time and standard loading conditions. AB - Aims: Load dependence is an important source of variation in left ventricular (LV) deformation. This impacts on the precision of information obtained from serial measurements. However, it is clinically important to distinguish actual myocardial dysfunction from changes associated with altered loading conditions. We sought to investigate the association of changes of loading parameters with changes in LV longitudinal (GLS) and circumferential (GCS) strains. Methods and results: Baseline and a 12-month follow-up 2D echocardiograms were performed in 191 Stage A heart failure patients with uncomplicated hypertension. These patients underwent simultaneous measurement of conventional and central blood pressures (BPs) and haemodynamic measurements by applanation tonometry. Significant, but weak correlations (r = 0.15-0.28) of LV strain parameters and their changes over the follow-up period were shown for the majority of LV afterload-associated variables, including central and brachial systolic, diastolic, and mean BPs; 24-h systolic and diastolic BPs; peak reservoir and excess pressures; central augmented pressure (CAP) and pulse pressure; augmentation index; and arterial elastance index (EaI). Central mean BP, EaI, and changes in CAP and EaI over follow-up were independent contributors to LV deformation in multivariable analysis. No improvement in the Bland-Altman 95% limits of agreement and correlation coefficients was seen with LV afterload correction of GLS and GCS using central BP indices. Conclusions: LV longitudinal and circumferential strains in a population without apparent heart disease is relatively insusceptible to changes in LV afterload within physiological range, which, therefore, seem unlikely to be a significant confounder in repeated GLS or GCS observations. PMID- 27369852 TI - Immunologic outcome in elderly kidney transplant recipients: is it time for HLA DR matching? AB - BACKGROUND: The Eurotransplant Senior Program (ESP) neglects HLA matching for elderly (>=65 years) kidney transplant recipients (KTR). Few data regarding the influence of DR matching on clinical and immunologic outcome in elderly KTR exist. METHODS: This retrospective long-term observational study included 244 elderly out of n = 972 adult KTR between 2004 and 2014. Data analysis included patient and graft survival, biopsy-proven rejections [T-cell-mediated rejections (TCMR) and antibody-mediated rejections] and development of de novo donor specific HLA antibodies (DSA). Outcome data were assessed over a maximum period of 10 years. RESULTS: Due to the nature of the ESP, elderly KTR showed significantly more HLA mismatches, shorter time on dialysis and shorter cold ischaemia time. Elderly KTR had significantly worse graft and patient survival, and after 7 years, the rate of de novo DSA (33 versus 25%, P = 0.034) and TCMR (39 versus 27%, P < 0.001) was significantly higher compared with younger KTR. Multivariate analysis identified donor age, delayed graft function and HLA-DR mismatches as independent risk factors for TCMR. Within the group of elderly KTR, HLA-DR mismatches were associated with a significantly higher incidence of TCMR and development of de novo DSA. Occurrence of TCMR and de novo DSA in elderly KTR resulted in significantly worse graft survival. CONCLUSIONS: In elderly KTR, HLA DR mismatches are independent risk factors for TCMR and the development of all classes of de novo DSA, both of which significantly impair graft survival. Introduction of HLA-DR matching in elderly KTR might significantly improve immunologic and overall outcome. PMID- 27369853 TI - Potential role of effector memory T cells in chronic T cell-mediated kidney graft rejection. AB - BACKGROUND: Chronic T cell-mediated rejection (TCMR) in kidney graft is characterized by reduction of the vessel lumen with marked intimal thickening, fibrous hyperplasia of the small renal arteries and leukocyte infiltrates. The aim of this study was to find specific gene expression profiles in chronic TCMR kidney biopsies. METHODS: RNA extracted from archival formalin-fixed, paraffin embedded renal biopsies was used for gene expression profiling. Our study included 14 patients with chronic TCMR and 10 with acute TCMR. Fifty-two cadaveric donors were used as controls. The results were validated in an independent set of kidney biopsies. RESULTS: We identified 616 and 243 differentially expressed genes with a fold change >=1.5 and a false discovery rate <0.05 in chronic and acute TCMR, respectively. Pathway analysis revealed upregulation of OX40 signalling. This pathway is involved in the generation of CD8+ effector memory T cells and the upregulation of killer cell lectin-like receptor G1 (KLRG-1), B lymphocyte-induced maturation protein 1 (BLIMP-1) and CD25, which characterize CD8+ effector memory T cells. However, the enhanced OX40 signalling pathway was specific to chronic TCMR; a significant increase of KLRG 1+/CD8+ and BLIMP-1+/CD8+ was only detected in these specimens. CONCLUSIONS: These results suggest the involvement of memory-committed CD8+ effector T cells in chronic TCMR. The generation of effector memory T cells is mediated by the OX40 gene pathway, and could be considered a future target for the specific treatment of chronic TCMR. PMID- 27369855 TI - Consensus-Based Recommendations for an Emergency Medicine Pain Management Curriculum. AB - BACKGROUND: Increased prescribing of opioid pain medications has paralleled the subsequent rise of prescription medication-related overdoses and deaths. We sought to define key aspects of a pain management curriculum for emergency medicine (EM) residents that achieve the balance between adequate pain control, limiting side effects, and not contributing to the current public health opioid crisis. METHODS: We convened a symposium to discuss pain management education in EM and define the needs and objectives of an EM-specific pain management curriculum. Multiple pertinent topics were identified a priori and presented before consensus work. Subgroups then sought to define perceived gaps and needs, to set a future direction for development of a focused curriculum, and to prioritize the research needed to evaluate and measure the impact of a new curriculum. RESULTS: The group determined that an EM pain management curriculum should include education on both opioid and nonopioid analgesics as well as nonpharmacologic pain strategies. A broad survey is needed to better define current knowledge gaps and needs. To optimize the impact of any curriculum, a modular, multimodal, and primarily case-based approach linked to achieving milestones is best. Subsequent research should focus on the impact of curricular reform on learner knowledge and patient outcomes, not just prescribing changes. CONCLUSIONS: This consensus group offers a path forward to enhance the evidence, knowledge, and practice transformation needed to improve emergency analgesia. PMID- 27369854 TI - Analysis of an echovirus 18 outbreak in Thuringia, Germany: insights into the molecular epidemiology and evolution of several enterovirus species B members. AB - In October and November 2010, six children and one woman were presented with symptoms of aseptic meningitis in Jena, Thuringia, Germany. Enterovirus RNA was detected in the cerebrospinal fluid of all patients by RT-PCR, and preliminary molecular typing revealed echovirus 18 (E-18) as causative agent. Virus isolates were obtained from stool samples of three patients and several contact persons. Again, most isolates were typed as E-18. In addition, coxsackievirus B5 (CV-B5) and echovirus 25 (E-25) were found to co-circulate. As only few complete E-18 sequences are available in GenBank, the entire genomes of these isolates were determined using direct RNA-sequencing technology. We did not find evidence for recombination between E-18, E-25 or CV-B5 during the outbreak. Viral protein 1 gene sequences and the cognate 3D polymerase gene sequences of each isolate and GenBank sequences were analysed in order to define type-specific recombination groups (recogroups). PMID- 27369856 TI - Primary Bacterial Gluteal Pyomyositis: A Rare Disease in Temperate Climates Presenting as Suspected Septic Arthritis of the Hip. AB - BACKGROUND: In nations with temperate climates, primary polymyositis is a rare, life-threatening bacterial infection that can mimic various clinical diseases depending on the area involved, leading to delayed diagnosis and management. CASE REPORT: We describe a young postpartum woman who presented to the emergency department with hip pain that was initially suspected to be caused by septic arthritis. However, hip arthrocentesis was negative, and a magnetic resonance imaging scan revealed extensive pyomyositis of the gluteal muscles. She underwent surgical debridement and was given parenteral antibiotics with good clinical recovery. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We emphasize that cases of pyomyositis in temperate countries are often diagnosed late and therefore delay life- and potentially limb-saving treatment. For patients who present with hip and thigh pain and clinical features of sepsis, pyomyositis should be considered in the differential diagnosis and an early magnetic resonance imaging scan should be performed to confirm the diagnosis and reduce the high morbidity and mortality associated with this emerging disease. PMID- 27369857 TI - Lidocaine Toxicity During Attempted Epistaxis Cautery. AB - BACKGROUND: Epistaxis is a common problem that occurs in up to 60% of the general population, and is a common emergency department (ED) complaint. The use of lidocaine for analgesia is common when cauterization is required for bleeds that are refractory to manual compression. Although the use of lidocaine is generally thought of as a benign intervention, it is not completely without risk. CASE REPORT: We present the case of a 19-year-old man who presented to the ED with persistent anterior epistaxis. He developed severe lidocaine toxicity resulting from topical anesthesia applied prior to intranasal cautery for the epistaxis. This toxicity, which manifested as seizures, bradycardia, hypotension, nausea, and emesis, was rapidly recognized and appropriately treated, with a good clinical outcome for the patient. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We present this case to increase awareness among emergency physicians of the potential complications of the intranasal use of topical lidocaine, something that is generally considered a benign intervention. We also discuss the pathophysiology and management of lidocaine toxicity. PMID- 27369858 TI - Comparative Performance of Glidescope Videolaryngoscope with Direct Laryngoscope for Emergency Intubation. PMID- 27369859 TI - Refractory Ventricular Fibrillation Successfully Cardioverted With Dual Sequential Defibrillation. AB - BACKGROUND: Current guidelines for the treatment of adult patients in cardiac arrest are supplied by the American Heart Association through basic life support and advanced cardiovascular life support (ACLS) provider courses. When treatments defined by the ACLS guidelines are unsuccessful in terminating a lethal dysrhythmia, the use of alternative strategies may prove useful. In this case, two defibrillators were used to deliver a greater than normal energy waveform over an extended time interval to return a patient to a normal sinus rhythm. CASE REPORT: A 56-year-old woman presented to the emergency department with complaints of chest pain, nausea, and vomiting. The patient's initial work-up, including an electrocardiogram and cardiac troponin, did not show evidence of acute ischemia, and she was admitted to the observation unit for further evaluation. While in the emergency department, the patient developed ventricular fibrillation, and ACLS was initiated. After four unsuccessful defibrillation attempts, a second defibrillator was placed on the patient, and the two were activated almost simultaneously. The patient had immediate return of spontaneous circulation, underwent cardiac catheterization, and was discharged home 1 week later. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case shows that dual sequential defibrillation may be a successful method for terminating refractory ventricular fibrillation. Further investigation on cardiac resuscitation should be conducted to standardize the dual sequential defibrillation delivery procedure. Until such guidelines are established, physicians should take this treatment into consideration when standard ACLS measures have failed to successfully terminate refractory ventricular fibrillation. PMID- 27369860 TI - Takotsubo Cardiomyopathy After Acute Pulmonary Embolus. PMID- 27369861 TI - Point of Care Ultrasound Diagnosis of Empyema. AB - BACKGROUND: Emergency ultrasonography is an efficient and cost effective tool for patients who are in respiratory distress. Chest radiographs can yield limited information for these patients. Computed tomography scans have long been the criterion standard for advanced imaging in patients with respiratory complaints, but point of care ultrasound (POCUS) can be performed at bedside, does not expose the patient to radiation, and at times may provide more information than a computed tomography scan. CASE REPORT: A 60-year-old man with a medical history of hypertension presented to the emergency department complaining of a productive cough associated with fever, weakness, and progressively worsening dyspnea on exertion over the previous 1 to 2 weeks. The physical examination was remarkable for rhonchi in the right upper lobe and diminished breath sounds throughout the right lung. POCUS was performed, and the results revealed severe atelectasis and hepatization of the right lung parenchyma with visualized air bronchograms. Complex hypoechoic material with a posterior spine sign was noted, which increased concern for complex consolidation and effusion. The diagnosis of pneumonia with empyema was made. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: POCUS has become a much more commonly used imaging modality within many emergency departments. Ultrasound is more sensitive than chest radiographs for identifying pathologies such as pneumothorax and simple effusions. This case shows how well POCUS can diagnose empyema even in the setting of diagnostic uncertainty of computed tomographic imaging. PMID- 27369862 TI - Toll-like receptor 1 variation increases the risk of transplant-related mortality in hematologic malignancies. AB - Toll-like receptor 1 (TLR1) genetic variant (rs5743551, -7202A>G) has been reported to be associated with susceptibility to various infectious diseases. We retrospectively examined the impact of TLR1 variation on transplant outcomes in a cohort of 320 patients who underwent unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies. A multivariate analysis showed that the G/G genotype in the recipients and the donors was associated with a significantly lower 3-year transplant-related mortality (TRM). The recipient G/G genotype also resulted in a better 3-year progression-free survival. This study suggests that the recipient and donor TLR1 G/G genotypes are comparably associated with a reduced risk of death that was not related to relapse. Thus, TLR1 genotyping may be useful for selecting the donor, managing patients in a risk-adapted manner, and creating therapeutic strategies to prevent complications after hematopoietic stem cell transplantation. PMID- 27369863 TI - Part II: Functional delivery of a neurotherapeutic gene to neural stem cells using minicircle DNA and nanoparticles: Translational advantages for regenerative neurology. AB - Both neurotrophin-based therapy and neural stem cell (NSC)-based strategies have progressed to clinical trials for treatment of neurological diseases and injuries. Brain-derived neurotrophic factor (BDNF) in particular can confer neuroprotective and neuro-regenerative effects in preclinical studies, complementing the cell replacement benefits of NSCs. Therefore, combining both approaches by genetically-engineering NSCs to express BDNF is an attractive approach to achieve combinatorial therapy for complex neural injuries. Current genetic engineering approaches almost exclusively employ viral vectors for gene delivery to NSCs though safety and scalability pose major concerns for clinical translation and applicability. Magnetofection, a non-viral gene transfer approach deploying magnetic nanoparticles and DNA with magnetic fields offers a safe alternative but significant improvements are required to enhance its clinical application for delivery of large sized therapeutic plasmids. Here, we demonstrate for the first time the feasibility of using minicircles with magnetofection technology to safely engineer NSCs to overexpress BDNF. Primary mouse NSCs overexpressing BDNF generated increased daughter neuronal cell numbers post-differentiation, with accelerated maturation over a four-week period. Based on our findings we highlight the clinical potential of minicircle/magnetofection technology for therapeutic delivery of key neurotrophic agents. PMID- 27369865 TI - Development of antibody-siRNA conjugate targeted to cardiac and skeletal muscles. AB - Despite considerable efforts to develop efficient carriers, the major target organ of short-interfering RNAs (siRNAs) remains limited to the liver. Expanding the application outside the liver is required to increase the value of siRNAs. Here we report on a novel platform targeted to muscular organs by conjugation of siRNAs with anti-CD71 Fab' fragment. This conjugate showed durable gene-silencing in the heart and skeletal muscle for one month after intravenous administration in normal mice. In particular, 1MUg siRNA conjugate showed significant gene silencing in the gastrocnemius when injected intramuscularly. In a mouse model of peripheral artery disease, the treatment with myostatin-targeting siRNA conjugate by intramuscular injection resulted in significant silencing of myostatin and hypertrophy of the gastrocnemius, which was translated into the recovery of running performance. These data demonstrate the utility of antibody conjugation for siRNA delivery and the therapeutic potential for muscular diseases. PMID- 27369864 TI - Anti-PEG antibodies in the clinic: Current issues and beyond PEGylation. AB - The technique of attaching the polymer polyethylene glycol (PEG), or PEGylation, has brought more than ten protein drugs into market. The surface conjugation of PEG on proteins prolongs their blood circulation time and reduces immunogenicity by increasing their hydrodynamic size and masking surface epitopes. Despite this success, an emerging body of literature highlights the presence of antibodies produced by the immune system that specifically recognize and bind to PEG (anti PEG Abs), including both pre-existing and treatment-induced Abs. More importantly, the existence of anti-PEG Abs has been correlated with loss of therapeutic efficacy and increase in adverse effects in several clinical reports examining different PEGylated therapeutics. To better understand the nature of anti-PEG immunity, we summarize a number of clinical reports and some critical animal studies regarding pre-existing and treatment-induced anti-PEG Abs. Various anti-PEG detection methods used in different studies were provided. Several protein modification technologies beyond PEGylation were also highlighted. PMID- 27369866 TI - What are the roles and valued attributes of a Trial Steering Committee? Ethnographic study of eight clinical trials facing challenges. AB - BACKGROUND: Clinical trials oversight by a Trial Steering Committee (TSC) is mandated by Good Clinical Practice. This study used qualitative methods to explore the role and valued attributes of the TSC to inform planned updates of Medical Research Council guidance and TSC terms of reference. METHODS: An ethnographic study was conducted during 2013-2014. TSC and Trial Management Group meetings from eight trials were observed and audio-recorded, and semi-structured interviews conducted with purposively sampled key informants: independent and non independent TSC members, trial sponsor representatives, funder representatives and chief investigators. The selected trials were currently recruiting and dealing with challenging scenarios. Data were analysed thematically and findings triangulated and integrated to give a multi-perspective account of the role and valued attributes of a TSC. RESULTS: Eight TSC meetings and six Trial Management Group meetings were observed. Sixty-five interviews were conducted with 51 informants. The two main roles played by the TSC were quality assurance and patient advocacy. Quality assurance involved being a 'critical friend' or a provider of 'tough love'. Factors influencing the ability of the TSC to fulfil this role included the TSC Chair, other independent TSC members and the model of the TSC and its fit with the trial subject. The role of the TSC as an advocate for patient well-being was perceived as paramount. Two attributes of TSC members emerged as critical: experience (of running a trial, trial oversight or in a clinical/methodological area) and independence. While independence was valued for giving impartiality, the lack of consensus about its definition and strict requirements of some funders made it difficult to operationalise. CONCLUSIONS: We found tensions and ambiguities in the roles expected of TSCs and the attributes valued of TSC members. In particular, the requirements of independence and experience could conflict, impacting the TSCs' quality assurance role. Concerns were raised regarding whose interests are served by funders' criteria of independence; in particular, funders' selection of TSC members was thought to potentially inhibit TSCs' ability to fulfil their patient advocacy role. These findings should be incorporated in revising guidance and terms of reference for TSCs. PMID- 27369868 TI - The outcome of treatment of chronic osteomyelitis according to an integrated approach. AB - Previous classification systems of chronic osteomyelitis have failed to provide objective and pragmatic guidelines for selection of the appropriate treatment strategy. In this study, we assessed the short-term treatment outcome in adult patients with long-bone chronic osteomyelitis prospectively where a modified host classification system was integrated with treatment strategy selection through a novel management algorithm. Twenty-six of the 28 enrolled patients were available for follow-up at a minimum of 12 months. The median patient age of was 36.5 years (range 18-72 years). Fourteen patients (54 %) were managed palliatively, and 11 patients (42 %) were managed through the implementation of a curative treatment strategy. One patient required alternative treatment in the form of an amputation. The overall success rate was 96.2 % (95 % CI 80.4-99.9 %) at a minimum of 12-months follow-up. Remission was achieved in all [11/11] patients treated curatively (one-sided 95 % CI 73.5-100.0 %). Palliative treatment was successful in 92.9 % [13/14] of cases (95 % CI 66.1-99.9 %). In patients with lower limb involvement, there was a statistically significant improvement of 28.3 (95 % CI 21.0-35.7; SD 17.0) in the AAOS Lower Limb Outcomes Instrument score (p value < 0.001). The integrated approach proposed in this study appears a useful guideline to the management of chronic osteomyelitis of long bones in adult patients in the developing world. Further investigation is required to validate the approach, and additional development of the algorithm may be required in order to render it useful in other clinical environments. PMID- 27369867 TI - Activating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T-cell-derived lymphomas. AB - Angioimmunoblastic T-cell lymphoma (AITL) and other lymphomas derived from follicular T-helper cells (TFH) represent a large proportion of peripheral T-cell lymphomas (PTCLs) with poorly understood pathogenesis and unfavorable treatment results. We investigated a series of 85 patients with AITL (n = 72) or other TFH derived PTCL (n = 13) by targeted deep sequencing of a gene panel enriched in T cell receptor (TCR) signaling elements. RHOA mutations were identified in 51 of 85 cases (60%) consisting of the highly recurrent dominant negative G17V variant in most cases and a novel K18N in 3 cases, the latter showing activating properties in in vitro assays. Moreover, half of the patients carried virtually mutually exclusive mutations in other TCR-related genes, most frequently in PLCG1 (14.1%), CD28 (9.4%, exclusively in AITL), PI3K elements (7%), CTNNB1 (6%), and GTF2I (6%). Using in vitro assays in transfected cells, we demonstrated that 9 of 10 PLCG1 and 3 of 3 CARD11 variants induced MALT1 protease activity and increased transcription from NFAT or NF-kappaB response element reporters, respectively. Collectively, the vast majority of variants in TCR-related genes could be classified as gain-of-function. Accordingly, the samples with mutations in TCR related genes other than RHOA had transcriptomic profiles enriched in signatures reflecting higher T-cell activation. Although no correlation with presenting clinical features nor significant impact on survival was observed, the presence of TCR-related mutations correlated with early disease progression. Thus, targeting of TCR-related events may hold promise for the treatment of TFH-derived lymphomas. PMID- 27369869 TI - Explosive synchronization coexists with classical synchronization in the Kuramoto model. AB - Explosive synchronization has recently been reported in a system of adaptively coupled Kuramoto oscillators, without any conditions on the frequency or degree of the nodes. Here, we find that, in fact, the explosive phase coexists with the standard phase of the Kuramoto oscillators. We determine this by extending the mean-field theory of adaptively coupled oscillators with full coupling to the case with partial coupling of a fraction f. This analysis shows that a metastable region exists for all finite values of f > 0, and therefore explosive synchronization is expected for any perturbation of adaptively coupling added to the standard Kuramoto model. We verify this theory with GPU-accelerated simulations on very large networks (N ~ 10(6)) and find that, in fact, an explosive transition with hysteresis is observed for all finite couplings. By demonstrating that explosive transitions coexist with standard transitions in the limit of f -> 0, we show that this behavior is far more likely to occur naturally than was previously believed. PMID- 27369870 TI - Quantifying Instrumental Artifacts in Folding Kinetics Measured by Single Molecule Force Spectroscopy. AB - Force spectroscopy is commonly used to measure the kinetics of processes occurring in single biological molecules. These measurements involve attaching the molecule of interest to micron-sized or larger force probes via compliant linkers. Recent theoretical work has described how the properties of the probes and linkers can alter the observed kinetics from the intrinsic behavior of the molecule in isolation. We applied this theory to estimate the errors in measurements of folding made using optical tweezers. Errors in the folding rates arising from instrument artifacts were only ~20% for constant-force measurements of DNA hairpins with typical choices of linker length and probe size. Measurements of transition paths using a constant trap position at high trap stiffness were also found to be in the low-artifact limit. These results indicate that typical optical trap measurements of kinetics reflect the dynamics of the molecule fairly well, and suggest practical limitations on experimental design to ensure reliable kinetic measurements. PMID- 27369872 TI - Decompressive Hemicraniectomy in the Age of Personalized Medicine. PMID- 27369871 TI - Maternal overweight and obesity and risk of pre-eclampsia in women with type 1 diabetes or type 2 diabetes. AB - AIMS/HYPOTHESIS: Women with type 1 or type 2 diabetes are at increased risk of pre-eclampsia. Overweight and obesity are associated with an increased risk of pre-eclampsia in women without diabetes. The aim of the study was to investigate the impact of maternal overweight and obesity on the risk of pre-eclampsia in women with type 1 diabetes or type 2 diabetes. METHODS: In a population-based cohort study including singleton births in Sweden, we estimated the risk of pre eclampsia among women with type 1 diabetes (n = 7062) and type 2 diabetes (n = 886), and investigated whether maternal overweight (BMI 25-29.9 kg/m(2)) and obesity (BMI >=30.0 kg/m(2)) modified the risk. Logistic regression analyses were used to estimate crude and adjusted ORs with 95% CIs, using women without diabetes as the reference group (n = 1,509,525). RESULTS: Compared with women without diabetes, the adjusted ORs for pre-eclampsia in women with type 1 and type 2 diabetes were 5.74 (95% CI 5.31, 6.20) and 2.11 (95% CI 1.65, 2.70), respectively. The corresponding risks of pre-eclampsia combined with preterm birth were even higher. Risks of pre-eclampsia increased with maternal overweight (BMI 25-29.9 kg/m(2)) and obesity (BMI >=30.0 kg/m(2)), foremost in women without diabetes, to a lesser extent in women with type 1 diabetes but not in women with type 2 diabetes. CONCLUSIONS/INTERPRETATION: Maternal overweight and obesity increased risks of pre-eclampsia in women with type 1 diabetes but not in women with type 2 diabetes. Even so, considering associations between maternal BMI and overall maternal and offspring risk, all women (with and without diabetes) should aim for a normal weight before pregnancy. PMID- 27369873 TI - A novel algorithm to predict the QT interval during intrinsic atrioventricular conduction from an electrocardiogram obtained during ventricular pacing. AB - BACKGROUND: QT interval prolongation is a major arrhythmia risk factor. Standard QT interval limits are defined for preserved intrinsic atrioventricular and interventricular conduction. However, ventricular pacing (VP) prolongs the QRS duration, induces electrical remodeling, and therefore obscures the intrinsic QT interval. No consensus exists on QT interval monitoring during VP. OBJECTIVE: The aim of this study was to develop an algorithm to predict the QT interval during intrinsic conduction (IC) from the VP electrocardiogram. METHODS: We measured electrocardiographic intervals QRS, QT, QTpeak, JTpeak, and TpeakTend in 38 participants with cardiac devices and preserved atrioventricular and interventricular conduction. We performed paired measurements in AAI (IC) and DDD (VP) pacing modes at equal heart rates at baseline and after 1 week of VP. We fit linear mixed models to predict IC QT intervals from VP intervals and compared their fit with other proposed methods of IC QT interval estimation. RESULTS: After 1 week of VP, the IC QT interval prolonged while the VP QT interval shortened from their respective baseline values. VP QT interval shortening was due to TpeakTend interval shortening. JTpeak and QTpeak intervals prolonged in both pacing modes at 1 week. A formula using VP QTpeak interval and heart rate closely predicted the IC QT interval (r = 0.94), outperforming other methods, including subtraction of "excess" QRS duration from the actual QT interval (r = 0.64) and subtraction of fixed values from heart rate-corrected QT interval (r = 0.58 and r = 0.69). Validation in 2000 bootstrapped data sets confirmed the model's performance (r = 0.93) compared to others (r = 0.43-0.58). CONCLUSION: In patients with VP, a formula using the QTpeak interval accurately predicts the intrinsic QT interval. PMID- 27369874 TI - [Not Available]. PMID- 27369875 TI - [Not Available]. PMID- 27369876 TI - [Not Available]. PMID- 27369878 TI - [Not Available]. PMID- 27369877 TI - [Not Available]. PMID- 27369879 TI - [Not Available]. PMID- 27369880 TI - [Not Available]. PMID- 27369881 TI - [Not Available]. PMID- 27369882 TI - [Not Available]. PMID- 27369883 TI - [Not Available]. PMID- 27369884 TI - [Not Available]. PMID- 27369885 TI - [Not Available]. PMID- 27369886 TI - [Not Available]. PMID- 27369887 TI - [Not Available]. PMID- 27369888 TI - [Not Available]. PMID- 27369889 TI - [Not Available]. PMID- 27369891 TI - [Not Available]. PMID- 27369890 TI - [Not Available]. PMID- 27369892 TI - [Not Available]. PMID- 27369893 TI - [Not Available]. PMID- 27369894 TI - [Not Available]. PMID- 27369895 TI - [Not Available]. PMID- 27369896 TI - A Novel Protocol for Directed Differentiation of C9orf72-Associated Human Induced Pluripotent Stem Cells Into Contractile Skeletal Myotubes. AB - : : Induced pluripotent stem cells (iPSCs) offer an unlimited resource of cells to be used for the study of underlying molecular biology of disease, therapeutic drug screening, and transplant-based regenerative medicine. However, methods for the directed differentiation of skeletal muscle for these purposes remain scarce and incomplete. Here, we present a novel, small molecule-based protocol for the generation of multinucleated skeletal myotubes using eight independent iPSC lines. Through combinatorial inhibition of phosphoinositide 3-kinase (PI3K) and glycogen synthase kinase 3beta (GSK3beta) with addition of bone morphogenic protein 4 (BMP4) and fibroblast growth factor 2 (FGF2), we report up to 64% conversion of iPSCs into the myogenic program by day 36 as indicated by MYOG+ cell populations. These cells began to exhibit spontaneous contractions as early as 34 days in vitro in the presence of a serum-free medium formulation. We used this protocol to obtain iPSC-derived muscle cells from frontotemporal dementia (FTD) patients harboring C9orf72 hexanucleotide repeat expansions (rGGGGCC), sporadic FTD, and unaffected controls. iPSCs derived from rGGGGCC carriers contained RNA foci but did not vary in differentiation efficiency when compared to unaffected controls nor display mislocalized TDP-43 after as many as 120 days in vitro. This study presents a rapid, efficient, and transgene-free method for generating multinucleated skeletal myotubes from iPSCs and a resource for further modeling the role of skeletal muscle in amyotrophic lateral sclerosis and other motor neuron diseases. SIGNIFICANCE: Protocols to produce skeletal myotubes for disease modeling or therapy are scarce and incomplete. The present study efficiently generates functional skeletal myotubes from human induced pluripotent stem cells using a small molecule-based approach. Using this strategy, terminal myogenic induction of up to 64% in 36 days and spontaneously contractile myotubes within 34 days were achieved. Myotubes derived from patients carrying the C9orf72 repeat expansion show no change in differentiation efficiency and normal TDP-43 localization after as many as 120 days in vitro when compared to unaffected controls. This study provides an efficient, novel protocol for the generation of skeletal myotubes from human induced pluripotent stem cells that may serve as a valuable tool in drug discovery and modeling of musculoskeletal and neuromuscular diseases. PMID- 27369897 TI - Impact of Feeding Strategies on the Scalable Expansion of Human Pluripotent Stem Cells in Single-Use Stirred Tank Bioreactors. AB - : : The routine application of human pluripotent stem cells (hPSCs) and their derivatives in biomedicine and drug discovery will require the constant supply of high-quality cells by defined processes. Culturing hPSCs as cell-only aggregates in (three-dimensional [3D]) suspension has the potential to overcome numerous limitations of conventional surface-adherent (two-dimensional [2D]) cultivation. Utilizing single-use instrumented stirred-tank bioreactors, we showed that perfusion resulted in a more homogeneous culture environment and enabled superior cell densities of 2.85 * 106 cells per milliliter and 47% higher cell yields compared with conventional repeated batch cultures. Flow cytometry, quantitative reverse-transcriptase polymerase chain reaction, and global gene expression analysis revealed a high similarity across 3D suspension and 2D precultures, underscoring that matrix-free hPSC culture efficiently supports maintenance of pluripotency. Interestingly, physiological data and gene expression assessment indicated distinct changes of the cells' energy metabolism, suggesting a culture induced switch from glycolysis to oxidative phosphorylation in the absence of hPSC differentiation. Our data highlight the plasticity of hPSCs' energy metabolism and provide clear physiological and molecular targets for process monitoring and further development. This study paves the way toward more efficient GMP-compliant cell production and underscores the enormous process development potential of hPSCs in suspension culture. SIGNIFICANCE: Human pluripotent stem cells (hPSCs) are a unique source for the, in principle, unlimited production of functional human cell types in vitro, which are of high value for therapeutic and industrial applications. This study applied single-use, clinically compliant bioreactor technology to develop advanced, matrix-free, and more efficient culture conditions for the mass production of hPSCs in scalable suspension culture. Using extensive analytical tools to compare established conditions with this novel culture strategy, unexpected physiological features of hPSCs were discovered. These data allow a more rational process development, providing significant progress in the field of translational stem cell research and medicine. PMID- 27369900 TI - [Not Available]. PMID- 27369901 TI - [Not Available]. PMID- 27369898 TI - Type IV pili promote early biofilm formation by Clostridium difficile. AB - Increasing morbidity and mortality from Clostridium difficile infection (CDI) present an enormous challenge to healthcare systems. Clostridium difficile express type IV pili (T4P), but their function remains unclear. Many chronic and recurrent bacterial infections result from biofilms, surface-associated bacterial communities embedded in an extracellular matrix. CDI may be biofilm mediated; T4P are important for biofilm formation in a number of organisms. We evaluate the role of T4P in C. difficile biofilm formation using RNA sequencing, mutagenesis and complementation of the gene encoding the major pilin pilA1, and microscopy. RNA sequencing demonstrates that, in comparison to other growth phenotypes, C. difficile growing in a biofilm has a distinct RNA expression profile, with significant differences in T4P gene expression. Microscopy of T4P-expressing and T4P-deficient strains suggests that T4P play an important role in early biofilm formation. A non-piliated pilA1 mutant forms an initial biofilm of significantly reduced mass and thickness in comparison to the wild type. Complementation of the pilA1 mutant strain leads to formation of a biofilm which resembles the wild-type biofilm. These findings suggest that T4P play an important role in early biofilm formation. Novel strategies for confronting biofilm infections are emerging; our data suggest that similar strategies should be investigated in CDI. PMID- 27369903 TI - [Not Available]. PMID- 27369902 TI - [Not Available]. PMID- 27369899 TI - Intracellular disassembly and activity of pertussis toxin require interaction with ATP. AB - The active subunit (S1) of pertussis toxin (PT), a major virulence factor of Bordetella pertussis, ADP-ribosylates Gi proteins in the mammalian cell cytosol to inhibit GPCR signaling. The intracellular pathway of PT includes endocytosis and retrograde transport to the trans-Golgi network (TGN) and endoplasmic reticulum (ER). Subsequent translocation of S1 to the cytosol is presumably preceded by dissociation from the holotoxin. In vitro, such dissociation is stimulated by interaction of PT with ATP. To investigate the role of this interaction in cellular events, we engineered a form of PT (PTDM) with changes to two amino acids involved in the interaction with ATP. PTDM was reduced in (1) binding to ATP, (2) dissociability by interaction with ATP, (3) in vitro enzymatic activity and (4) cellular ADP-ribosylation activity. In cells treated with PTDM carrying target sequences for organelle-specific modifications, normal transport to the TGN and ER occurred, but N-glycosylation patterns of the S1 and S4 subunits were consistent with an inability of PTDM to dissociate in the ER. These results indicate a requirement for interaction with ATP for PT dissociation in the ER and cellular activity. They also indicate that the retrograde transport route is the cellular intoxication pathway for PT. PMID- 27369905 TI - [Not Available]. PMID- 27369904 TI - [Not Available]. PMID- 27369906 TI - [Not Available]. PMID- 27369907 TI - [Not Available]. PMID- 27369908 TI - [Not Available]. PMID- 27369909 TI - [Not Available]. PMID- 27369911 TI - [Not Available]. PMID- 27369910 TI - [Not Available]. PMID- 27369913 TI - [Not Available]. PMID- 27369912 TI - [Not Available]. PMID- 27369914 TI - [Not Available]. PMID- 27369915 TI - [Not Available]. PMID- 27369917 TI - [Not Available]. PMID- 27369916 TI - [Not Available]. PMID- 27369918 TI - [Not Available]. PMID- 27369919 TI - [Not Available]. PMID- 27369920 TI - [Not Available]. PMID- 27369921 TI - [Not Available]. PMID- 27369922 TI - [Not Available]. PMID- 27369924 TI - [Not Available]. PMID- 27369923 TI - [Not Available]. PMID- 27369925 TI - [Not Available]. PMID- 27369926 TI - [Not Available]. PMID- 27369927 TI - [Not Available]. PMID- 27369929 TI - [Not Available]. PMID- 27369928 TI - [Not Available]. PMID- 27369930 TI - [Not Available]. PMID- 27369933 TI - [Not Available]. PMID- 27369932 TI - Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury. AB - Reductions in renal microvasculature density and increased lymphocyte activity may play critical roles in the progression of chronic kidney disease (CKD) following acute kidney injury (AKI) induced by ischemia/reperfusion injury (IRI). Vitamin D deficiency is associated with tubulointerstitial damage and fibrosis progression following IRI-AKI We evaluated the effect of vitamin D deficiency in sustained IRI-AKI, hypothesizing that such deficiency contributes to the early reduction in renal capillary density or alters the lymphocyte response to IRI Wistar rats were fed vitamin D-free or standard diets for 35 days. On day 28, rats were randomized into four groups: control, vitamin D deficient (VDD), bilateral IRI, and VDD+IRI Indices of renal injury and recovery were evaluated for up to 7 days following the surgical procedures. VDD rats showed reduced capillary density (by cablin staining), even in the absence of renal I/R. In comparison with VDD and IRI rats, VDD+IRI rats manifested a significant exacerbation of capillary rarefaction as well as higher urinary volume, kidney weight/body weight ratio, tissue injury scores, fibroblast-specific protein-1, and alpha-smooth muscle actin. VDD+IRI rats also had higher numbers of infiltrating activated CD4(+) and CD8(+) cells staining for interferon gamma and interleukin-17, with a significant elevation in the Th17/T-regulatory cell ratio. These data suggest that vitamin D deficiency impairs renal repair responses to I/R injury, exacerbates changes in renal capillary density, as well as promoting fibrosis and inflammation, which may contribute to the transition from AKI to CKD. PMID- 27369935 TI - [Not Available]. PMID- 27369934 TI - [Not Available]. PMID- 27369936 TI - [Not Available]. PMID- 27369937 TI - [Not Available]. PMID- 27369938 TI - [Not Available]. PMID- 27369939 TI - [Not Available]. PMID- 27369940 TI - [Not Available]. PMID- 27369941 TI - [Not Available]. PMID- 27369942 TI - [Not Available]. PMID- 27369944 TI - [Not Available]. PMID- 27369943 TI - [Not Available]. PMID- 27369945 TI - [Not Available]. PMID- 27369946 TI - [Not Available]. PMID- 27369947 TI - [Not Available]. PMID- 27369948 TI - [Not Available]. PMID- 27369949 TI - [Not Available]. PMID- 27369950 TI - [Not Available]. PMID- 27369951 TI - Fifty top-cited fracture articles from China: a systematic review and bibliometric analysis. AB - BACKGROUND: With more than 50,000 orthopaedic surgeons, China is having an increasing impact on fracture surgery research. However, the most influential Chinese articles on fracture surgery have not been determined. This study aimed to characterise the most-cited articles on fracture surgery by Chinese authors to provide insight into the fracture research in China. METHODS: The Web of Science was used to search for citations of fracture surgery articles that originated in China. The 50 most-cited articles were identified. The title, number of citations, year of publication, journal, article type, level of evidence, city, institution, and authors were recorded and evaluated. RESULTS: The 50 top-cited papers were published between 1984 and 2012. The most prolific decade began in the year 2000. These articles received 28 to 209 citations (mean 52), were written in English, and published in 12 journals. Injury was the most popular journal, with the largest number of articles (11) on the top 50 list. The region with the largest number of published articles was Hong Kong (20), followed by Kaohsiung (8), Shanghai (8), and Taipei (7). Most were clinical studies (39), while the remaining studies were basic science articles (11). The hip was the most common topic in the clinical studies. The most popular level of evidence was IV. CONCLUSIONS: This list of the top 50 publications identifies the most influential Chinese fracture surgery articles for the global community. This study presents insight into the historical contributions of Chinese researchers and the fracture surgery trends in China. PMID- 27369952 TI - [Not Available]. PMID- 27369953 TI - [Not Available]. PMID- 27369954 TI - [Not Available]. PMID- 27369955 TI - [Not Available]. PMID- 27369956 TI - [Not Available]. PMID- 27369957 TI - [Not Available]. PMID- 27369958 TI - [Not Available]. PMID- 27369959 TI - Preoperative hemostatic assessment: a new and simple bleeding questionnaire. AB - PURPOSE: Current recommendations for the assessment of the risk of perioperative bleeding limit coagulation testing to patients with a personal and/or family history of bleeding. As no simple preoperative screening questionnaire is currently available, we assessed the performance of a novel screening questionnaire for its ability to detect bleeding disorders. METHODS: A dichotomized, seven-point questionnaire named HEMSTOP (Hematoma, hEmorrhage, Menorrhagia, Surgery, Tooth extraction, Obstetrics, Parents) was applied to three groups of subjects: patients referred to hemostasis specialists for bleeding symptoms for whom any kind of perioperative hemostatic precautions were subsequently recommended (n = 38); patients referred to hemostasis specialists for whom precautions were not required (n = 75); healthy volunteers (n = 70). We calculated the sensitivity and specificity of HEMSTOP scores and compared them with the discriminative performances of standard blood coagulation assays (prothrombin time, activated partial thromboplastin time). RESULTS: Patients requiring perioperative hemostatic precautions had greater median [interquartile range] HEMSTOP scores (2 [2-3]) than patients not requiring precautions (1 [1-2]) and healthy controls (0 [0-0]); P < 0.001. A HEMSTOP score >= 2 had a specificity of 98.6% [95% confidence interval (CI), 92.3 to 100] and a sensitivity of 89.5% (95% CI, 75.2 to 97.1). The 26.3% (95% CI, 13.4 to 43.1) sensitivity of the standard coagulation times was much lower. CONCLUSION: The HEMSTOP score discriminates patients at an elevated risk for bleeding with recommended perioperative precautions from those without such recommendations as well as from healthy participants. Further evaluation of the HEMSTOP score is required for a better evaluation of its definitive usefulness to predict the risk of perioperative bleeding. PMID- 27369960 TI - [Not Available]. PMID- 27369961 TI - [Not Available]. PMID- 27369962 TI - [Not Available]. PMID- 27369963 TI - [Not Available]. PMID- 27369964 TI - Laparoscopic-assisted pull-through operation for Hirschsprung's disease: a systematic review and meta-analysis. AB - PURPOSE: In the last two decades, laparoscopic-assisted pull-through (LAPT) has gained much popularity in the treatment of Hirschsprung's disease. The aim of this meta-analysis was to determine the long-term outcome of patients treated laparoscopically. METHODS: A systematic literature-based search for relevant cohorts was performed using the terms "Hirschsprung's disease and Laparoscopy", "Laparoscopic-assisted pull-through outcome", "Laparoscopic-assisted Soave pull through" "Laparoscopic-assisted Swenson pull-through" and Laparoscopic-assisted Duhamel pull-through. The relevant cohorts of laparoscopic operated HD were systematically searched for outcome regarding continence, constipation, secondary surgery related to the laparoscopic approach and enterocolitis. Pooled incidence rates and odds ratios (ORs) with 95 % confidence intervals (CI) were calculated using standardized statistical methodology. RESULTS: Sixteen studies met defined inclusion criteria, reporting a total of 820 patients. All studies were retrospective case series, with variability in outcome assessment quality and length of follow-up. The median cohort size consisted of 28 patients (range 15 218). In the long-term follow-up, 97 patients (11.14 %) experienced constipation (OR 0.06, 95 % CI 0.05-0.08, p < 0.00001), 53 (6.46 %) incontinence/soiling (OR 0.01 95 % CI 0.01-0.01, p < 0.00001), 75 (9.14 %) recurrent enterocolitis (OR 0.02 95 % CI 0.01-0.02, p < 0.00001) and 69 (8.4 %) developed complications requiring secondary surgery (OR 0.01 95 % CI 0.01-0.02, p < 0.00001). Overall events in long-term follow-up occurred in 225 (27.5 %) patients (OR 0.24 95 % CI 0.20-0.30, p < 0.00001). CONCLUSIONS: This meta-analysis shows that nearly one third of the patients continue to have long-term bowel problems, such as constipation, soiling and recurrent enterocolitis following LAPT. Many patients treated by LAPT require secondary surgery. Large randomized studies with long term follow-up are necessary to determine the difference in outcome between LAPT and completely transanal pull-through operation. PMID- 27369965 TI - Effectiveness of calretinin and role of age in the diagnosis of Hirschsprung disease. AB - OBJECTIVE: Gold standard in Hirschsprung disease (HD) diagnosis is rectal suction biopsy (RSB) with hematoxylin and eosin and acetylcholinesterase (ACE) stainings. Sensitivity is 83-93 % and specificity is between 95 and 99 %. The rate of non conclusive results (NC) due to inadequate samples or variability in the interpretation is about 11-37.8 %. Interpretation is still difficult in neonates. Calretinin (C) is a calcium-binding protein, expressed in the nervous system. It has been introduced as a marker to improve the diagnosis accuracy in HD. We compare sensitivity, specificity between ACE and ACE + C and investigate whether the introduction of C could reduce the rate of inconclusive results. We also tried to define the most adequate age to obtain accurate results from RSB. METHODS: Data from patients undergoing rectal suction biopsies from 2005 to 2014 was analyzed. Until 2010 we used ACE; since 2011 we used ACE + C. The ROC curve analysis of the NC results regarding the age, showed an optimal cut-off point at 1.5 months (m). It divides the sample into two groups which we compared. RESULTS: We analyzed 91 patients. Results of the RSB: 40 HD (44 %), 34 no Hirschsprung (37.4 %) and 17 NC (18.7 %). Sensitivity = 97.5 %, specificity = 97.1 %, not including the NC (1 false positive, 1 false negative). Results depending on the staining: ACE (n = 58) (%) ACE + C (n = 33) (%) p Sensitivity 96 100 1 Specificity 94.7 100 1 NC 24.1 9.1 0.077 Results depending on the age: <1.5 m (n = 27) (%) >1.5 m (n = 64) (%) p Sensitivity 92.3 100 0.325 Specificity 100 96.8 1 NC 40.7 9.4 0.001 CONCLUSION: Calretinin decreases the rate of inconclusive results, but not significantly. The percentage of inconclusive results decreases in patients olders than 1.5 m. Further studies are necessary to determine if this technique is useful to improve RSB results in infants younger than 1.5 months. PMID- 27369967 TI - [Not Available]. PMID- 27369966 TI - The role of coping strategies on health-related quality of life in adults with anorectal malformations. AB - PURPOSE: Coping strategies have been acknowledged as crucial for the well-being and for health-related quality of life (HRQoL). The main aim of the present study is to determine whether different types of coping strategies predict HRQoL in patients born with ARM, above and beyond the variance explained by fecal and urinary continence. METHODS: 71 adult patients from the Italian Parents' and Patients' Organization for Anorectal Malformations (AIMAR) participated in the study. Participants completed measures of fecal and urinary continence of the Hirschsprung Disease/Anorectal Malformation Quality of Life (HAQL) (Hanneman et al. in Dis Col Rect 44:1650-1660, 2001), the Short Form Health Survey (SF-36) (Apolone and Mosconi in J Clin Epidemiol 51:1025-1036, 1998), and the Brief Coping Orientation to Problems Experienced (COPE) Inventory (Carver in Int J Behav Med 4:92-100, 1997), which measures different coping strategies: maladaptive, problem-focused and emotion-focused. RESULTS: Hierarchical regression analyses showed that fecal continence (beta = 0.53, p < 0.01) and urinary continence significantly predict (beta = 0.23, p < 0.05) Physical HRQoL. Fecal continence (beta = 0.36, p < 0.01) and maladaptive coping strategies significantly predict (beta = -0.27, p < 0.05) Mental HRQoL. CONCLUSION: Besides considering the importance of fecal and urinary continence for Physical HRQoL, these findings indicate that maladaptive coping strategies are associated with worse Mental HRQoL. Interventions aimed at enhancing the patients' HRQoL should target coping strategies by reducing denial, behavioral disengagement, substance abuse, and self-blame. PMID- 27369968 TI - [Not Available]. PMID- 27369969 TI - [Not Available]. PMID- 27369970 TI - [Not Available]. PMID- 27369972 TI - [Not Available]. PMID- 27369971 TI - [Not Available]. PMID- 27369974 TI - Comparison of selected approaches for urban roughness determination based on voronoi cells. AB - Wind speed is reduced above urban areas due to their high aerodynamic roughness. This not only holds for above the urban canopy. The local vertical wind profile is modified. Aerodynamic roughness (both roughness length and displacement height) therefore is relevant for many fields within human biometeorology, e.g. for the identification of ventilation paths, the concentration and dispersion of air pollutants at street level or to simulate wind speed and direction in urban environments and everything depending on them. Roughness, thus, also shows strong influence on human thermal comfort. Currently, roughness parameters are mostly estimated using classifications. However, such classifications only provide limited assessment of roughness in urban areas. In order to calculate spatially resolved roughness on the micro-scale, three different approaches were implemented in the SkyHelios model. For all of them, the urban area is divided into reference areas for each of the obstacles using a voronoi diagram. The three approaches are based on building and [+one of them also on] vegetation (trees and forests) data. They were compared for the city of Stuttgart, Germany. Results show that the approach after Bottema and Mestayer (J Wind Eng Ind Aerodyn 74 76:163-173 1998) on the spatial basis of a voronoi diagram provides the most plausible results. PMID- 27369975 TI - Impact of Calcification on Clinical Outcomes After Endovascular Therapy for Superficial Femoral Artery Disease: Assessment Using the Peripheral Artery Calcification Scoring System. AB - PURPOSE: To investigate whether the severity of lesion calcification assessed by the novel peripheral artery calcification scoring system (PACSS) was associated with clinical outcomes after endovascular therapy (EVT) for superficial femoral artery (SFA) lesions. METHODS: A retrospective analysis was conducted of 394 consecutive patients (mean age 72+/-8 years; 290 men) with intermittent claudication [223 (57%) with diabetes, 81 (21%) on hemodialysis] who underwent successful EVT for de novo SFA lesions [length 152.1+/-95.7 mm; 199 (50%) TransAtlantic Inter-Society Consensus II class C/D] between January 2010 and December 2013. The patients were retrospectively categorized using the PACSS classification (grades 0-4: no visible calcification of the target lesion, unilateral wall calcification <5 cm, unilateral calcification >=5 cm, bilateral wall calcification <5 cm, and bilateral calcification >=5 cm, respectively). The main outcome was primary patency, while the secondary outcome measures were mortality and major adverse limb events [MALE: any intervention (repeat EVT or surgical revision) or major (above ankle) amputation]. Cox proportional hazards analysis was used to explore whether the PACSS classification was an independent predictor of clinical outcomes. Results are presented as the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: The distribution of PACSS grades was 0 in 54%, grade 1 in 16%, grade 2 in 12%, grade 3 in 9%, and grade 4 in 9%. The 2 year primary patency rates in these grades, respectively, were 70.0%, 66.6%, 72.1%, 55.6%, and 36.3% (p<0.001). After multivariate analysis, PACSS grade 4 (HR 2.74, 95% CI 1.56 to 4.83, p<0.001), diabetes (HR 1.52, 95% CI 1.06 to 2.20, p=0.022), lesion length (HR 1.04, 95% CI 1.01 to 1.07, p=0.006), and vessel diameter (HR 0.80, 85% CI 0.65 to 0.98, p=0.038) were associated with loss of primary patency. PACSS grade 4 was also associated with MALE and mortality (p=0.048 and 0.011, respectively). Bare metal stent use (HR 0.47, 95% CI 0.30 to 0.73, p<0.001) was positively associated with primary patency. CONCLUSION: PACSS grade 4 calcification was independently associated with clinical outcomes after EVT for de novo SFA lesions. PMID- 27369976 TI - Influence of Repeat Intervention on the Risk of Major Amputation After Infrapopliteal Angioplasty for Critical Limb Ischemia. AB - PURPOSE: To assess the influence of repeat intervention on the risk of major amputation after infrapopliteal angioplasty for patients with critical limb ischemia (CLI). METHODS: A multicenter database of Japanese CLI patients was interrogated to identify patients who underwent balloon angioplasty for isolated infrapopliteal lesions from April 2004 to December 2012. In that time frame, 1298 limbs of 1065 patients (mean age 72+/-10 years; 739 men) were eligible for this analysis. The prevalence of tissue loss was 76%, with 33% accompanied by infection. The association between repeat intervention and future risk for major amputation was evaluated using a mixed effects logistic regression model. A stratification analysis was also performed with baseline variables. A supplementary analysis compared baseline characteristics between the cases with and without repeat intervention. Hazard ratios (HR) and their 95% confidence intervals (CI) are reported. RESULTS: Median follow-up was 1.2 years (interquartile range 0.4-2.5), during which time 143 (11.0%) limbs had major amputations and 499 (38.4%) underwent repeat intervention. The mixed effects modeling revealed that repeat intervention was significantly associated with future risk for major amputation (unadjusted HR 3.01, 95% CI 2.05 to 4.41, p=0.001). From the stratification analysis, repeat intervention significantly increased future risk of major amputation in cases with regular dialysis (HR 3.35, 95% CI 2.14 to 5.26, p<0.001), whereas it did not in those without dialysis. The supplemental analysis showed that patients with repeat intervention within 1 year had a higher prevalence of nonambulatory status, regular dialysis, tissue loss, and infection at baseline compared to those without repeat intervention for 1 year. CONCLUSION: In the patients with CLI due to infrapopliteal lesions, the need for repeat intervention increased the risk of future major amputation. However, this correlation was not applicable to nondialysis patients. PMID- 27369979 TI - [Not Available]. PMID- 27369978 TI - [Not Available]. PMID- 27369980 TI - [Not Available]. PMID- 27369981 TI - [Not Available]. PMID- 27369977 TI - Detection of tumor-associated cells in cryopreserved peripheral blood mononuclear cell samples for retrospective analysis. AB - BACKGROUND: Cryopreserved peripheral blood mononuclear cells (PBMCs) are commonly collected in biobanks. However, little data exist regarding the preservation of tumor-associated cells in cryopreserved collections. The objective of this study was to determine the feasibility of using the CellSieveTM microfiltration assay for the isolation of circulating tumor cells (CTCs) and circulating cancer associated macrophage-like cells (CAMLs) from cryopreserved PBMC samples. METHODS: Blood samples spiked with breast (MCF-7), prostate (PC-3), and renal (786-O) cancer cell lines were used to establish analytical accuracy, efficiency, and reproducibility after cryopreservation. The spiked samples were processed through Ficoll separation, and cryopreservation was followed by thawing and microfiltration. RESULTS: MCF-7 cells were successfully retrieved with recovery efficiencies of 90.5 % without cryopreservation and 87.8 and 89.0 %, respectively, on day 7 and day 66 following cryopreservation. The corresponding recovery efficiencies of PC-3 cells were 83.3 % without cryopreservation and 85.3 and 84.7 %, respectively, after cryopreservation. Recovery efficiencies of 786-O cells were 92.7 % without cryopreservation, and 82.7 and 81.3 %, respectively, after cryopreservation. The recovered cells retained the morphologic characteristics and immunohistochemical markers that had been observed before freezing. The protocols were further validated by quantitation of CAMLs in blood samples from two patients with renal cell carcinoma (RCC). The recovery rates of CTCs and CAMLs from cryopreserved samples were not statistically significant different (P > 0.05) from matched fresh samples. CONCLUSIONS: To our knowledge, this is the first report that CAMLs could be cryopreserved and analyzed after thawing with microfiltration technology. The application of microfiltration technology to cryopreserved samples will enable much greater retrospective study of cancer patients in relation to long-term outcomes. PMID- 27369982 TI - [Not Available]. PMID- 27369985 TI - [Not Available]. PMID- 27369983 TI - [Not Available]. PMID- 27369984 TI - [Not Available]. PMID- 27369986 TI - [Not Available]. PMID- 27369987 TI - [Not Available]. PMID- 27369988 TI - [Not Available]. PMID- 27369989 TI - [Not Available]. PMID- 27369991 TI - [Not Available]. PMID- 27369990 TI - [Not Available]. PMID- 27369992 TI - [Not Available]. PMID- 27369993 TI - [Not Available]. PMID- 27369994 TI - [Not Available]. PMID- 27369995 TI - [Not Available]. PMID- 27369996 TI - [Not Available]. PMID- 27369998 TI - [Not Available]. PMID- 27369997 TI - [Not Available]. PMID- 27369999 TI - [Not Available]. PMID- 27370000 TI - [Not Available]. PMID- 27370002 TI - [Not Available]. PMID- 27370001 TI - [Not Available]. PMID- 27370003 TI - [Not Available]. PMID- 27370004 TI - [Not Available]. PMID- 27370005 TI - [Not Available]. PMID- 27370006 TI - [Not Available]. PMID- 27370007 TI - [Not Available]. PMID- 27370008 TI - [Not Available]. PMID- 27370009 TI - Volume-based Interval Training Program for Elite Tennis Players. AB - BACKGROUND: A sport-specific conditioning program can help tennis players train for competition or return to play from injury. This study determined the actual tennis serve volume in elite play and used these data to construct an interval training program based on stroke volume. HYPOTHESIS: There will be no differences in serve volume between male and female tennis players at the professional and junior levels. STUDY DESIGN: Retrospective cohort study. LEVEL OF EVIDENCE: Level 3. METHODS: Game day statistic scorecards were provided to the research team from the 2013 and 2014 United States Open and the 2014 Metropolia Orange Bowl International Tennis Championships. Serve volume data for both male and female players were extracted from the scorecards. Data included serves per match and per set. These data were used to construct a sport-specific tennis program to meet the demands of the serve. RESULTS: Professional male players serve 63 more serves per match than junior male players because of the greater number of sets played ( P < 0.01). Professional female players serve 10 more serves per match than junior female players playing the same number of sets ( P = 0.01). All male players hit 2 more total serves per set than all female players ( P < 0.01). Regardless of sex, professional players serve 4 more serves per set than junior players ( P < 0.01). The typical number of serves per set was 40 in elite-level tennis players, resulting in a 3:1 ratio of first to second serves. CONCLUSION: These data establish the "unit dose" of serves per match and/or per set for each group. CLINICAL RELEVANCE: Coaches and health care providers may use these data in estimating loads per tournament/season and to prepare tennis athletes for individual competition and/or as they return to play after an injury. PMID- 27370010 TI - A rare coronary anomaly consisting of a single right coronary ostium in an adult undergoing surgical coronary revascularization: a case report and review of the literature. AB - BACKGROUND: Coronary arteries originating from the right coronary ostium in the ascending aorta represent a very rare anatomic presentation. Also, the presence of a single coronary ostium is an extremely rare finding. CASE PRESENTATION: We present the case of a 74-year-old Albanian man from Kosovo. He had unstable angina due to critical triple vessel disease and a single coronary artery originating from a single ostium in the right sinus of Valsalva with an anomalous course of his left anterior descending artery anteriorly to the right ventricular outflow tract as a "T-vessel" from which originated the proximal and distal left anterior descending artery, the circumflex artery originating from the mid portion of the right coronary artery which had a normal course. He underwent successful coronary revascularization consisting of three vein grafts to the right coronary artery, first diagonal and obtuse marginal artery, and left internal mammary artery anastomosed to left anterior descending artery. CONCLUSIONS: We describe a proposed IID1 pattern. After a careful revision of the literature, only six cases have been reported with a similar anomalous coronary origin. Only two out of six patients underwent surgical coronary revascularization. In our case the aberrant vessel arising from his right coronary artery coursed anteriorly to the right ventricle and continued as a left anterior descending artery at its mid portion which then continued distally as the distal left anterior descending artery and proximally as a proximal left anterior descending artery, having the shape of a "T vessel". The "T-vessel" configuration has never been reported in the literature. The reported case with its specific presentation adds further information on this rare form of anomalous origin of the coronary arteries, representing a first report of a configuration that we name the "T-vessel" of the left anterior descending artery. Diagnosis of the coronary anatomy is very important for the invasive cardiologist and cardiac surgeon in cases with a single coronary ostium, such as our case, so that they can proceed with the invasive or surgical treatment when critical coronary artery disease is present. PMID- 27370011 TI - Laparoscopic diverticulectomy: A systemised technique. AB - OBJECTIVES: To present an original technique for laparoscopic vesical diverticulectomy without the need for dissecting the diverticular wall, thereby making the procedure safe and significantly simpler. MATERIAL AND METHODS: Four patients were operated on between September 2014 and April 2016. The diagnosis was made by ultrasonography in all cases, and the study included blood and urine analyses with urine cultures, urine cytology, contrast-enhanced CT scans, prostate symptom questionnaire (International Prostate Symptom Score), flowmetry and cystoscopy. One case required transurethral prostate resection in a first time. RESULTS: The mean age of the patients was 64 years (range: 56-71). The mean diverticulum size was 4cm (range: 3-6). The location was retrotrigonal in all cases, on the left side in 2 cases, right retromeatic in 1 case and near the midline in 1 case. The mean surgical time was 146min (range, 120-180), shortening for each new case. There were no significant bleeding, complications or conversion to open surgery in any of the cases. The postoperative period had no incidences. The hospital stay was 3 days in 3 cases and 48h in the other case (mean, 3.5 days). The catheter was withdrawn in the outpatient clinic at 14 days. CONCLUSIONS: The initial experience with the technique described above shows it to be safe and reproducible, with results similar to other current laparoscopic techniques. Avoiding the dissection of the diverticular wall significantly reduces the technical difficulty of the procedure. PMID- 27370012 TI - Outcome of primary vitrectomy in phakic patients aged younger than 50 years with rhegmatogenous retinal detachments. AB - PURPOSE: To evaluate the visual outcome, primary anatomic success, and cataract progression of phakic eyes of patients aged younger than 50 years treated for rhegmatogenous retinal detachment (RRD) with primary pars plana vitrectomy (PPV). METHODS: This was a retrospective, observational, cross-sectional study. The data from 53 RRD patients undergoing PPV were analyzed. The time course changes in best-corrected visual acuity (BCVA) and cataract formation were examined. RESULTS: The 53 patients had a mean age of 37.8 years. Forty-eight eyes (90.6 %) achieved anatomic success after the primary surgery. The BCVA improved significantly after surgery (mean +/- SD -0.091 +/- 0.146) when compared with the baseline (mean +/- SD 0.214 +/- 0.597; P = 0.0001). No patient aged younger than 40 years (mean 32.5 years; range 17-39) developed significant lens opacity or received cataract surgery within the first 3 years. Of the patients aged older than 40 years (mean 43.8 years; range 40-49), 22 % developed significant lens opacity and received cataract surgery within the first 3 years. A significant difference was found in cataract progression between the two groups within the first 3 years (P = 0.0217), but not over the entire follow-up period (P = 0.1679). CONCLUSIONS: We found that lens-sparing PPV for RRD in patients aged younger than 50 years had a reasonable success rate, although cataract progression was evident during the follow-up period in patients aged older than 40 years. PMID- 27370014 TI - Erratum to: Feasibility and usefulness of ultrasonography in idiopathic intracranial hypertension or secondary intracranial hypertension. PMID- 27370013 TI - Comparison of treatment effect estimates of non-vitamin K antagonist oral anticoagulants versus warfarin between observational studies using propensity score methods and randomized controlled trials. AB - Emerging observational studies using propensity score (PS) methods assessed real world comparative effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in patients with non-valvular atrial fibrillation (AF). We aimed to compare treatment effect estimates of NOACs between PS studies and randomized controlled trials (RCTs). Electronic databases and conference proceedings were searched systematically. Primary outcomes included stroke or systemic embolism (SE) and major bleeding. A random-effects meta-analysis was performed to synthesize the data by pooling the PS- and RCT-derived hazard ratios (HRs) separately. The ratio of HRs (RHR) from the ratio of PS-derived HRs relative to RCT-derived HRs was used to determine whether there was a difference between estimates from PS studies and RCTs. There were 10 PS studies and 5 RCTs included for analysis. No significant difference of treatment effect estimates between the PS studies and RCTs was observed: RHR 1.11, 95 % CI 0.98-1.23 for stroke or SE; RHR 1.07, 95 % CI 0.87-1.34 for major bleeding. A significant association between NOACs and risk of stroke or SE was observed: HR 0.88, 95 % CI 0.83-0.94 for the PS studies; HR 0.79, 95 % CI 0.72-0.87 for the RCTs. However, no relationship between NOACs and risk of major bleeding was found: HR 0.91, 95 % CI 0.79-1.05 for the PS studies; HR 0.85, 95 % CI 0.73-1.00 for the RCTs. In this study, treatment effect estimates of NOACs versus warfarin in patients with non valvular AF from PS studies are found to be in agreement with those from RCTs. PMID- 27370015 TI - Gr-1intCD11b+ myeloid-derived suppressor cells accumulate in corneal allograft and improve corneal allograft survival. AB - We identified the characteristics of myeloid-derived suppressor cells (MDSCs) and investigated their mechanism of induction and their functional role in allograft rejection using a murine corneal allograft model. In mice, MDSCs coexpress CD11b and myeloid differentiation antigen Gr-1. Gr-1+CD11b+ cells infiltrated allografted corneas between 4 d and 4 wk after surgery; however, the frequencies of Gr-1+CD11b+ cells were not different between accepted and rejected allografts or in peripheral blood or BM. Of interest, Gr-1intCD11b+ cells, but not Gr 1hiCD11b+ cells, infiltrated the accepted graft early after surgery and expressed high levels of immunosuppressive cytokines, including IL-10, TGF-beta, and TNF related apoptosis-inducing ligand. This population remained until 4 wk after surgery. In vitro, only high dose (>100 ng/ml) of IFN-gamma plus GM-CSF could induce immunosuppressive cytokine expression in Gr-1intCD11b+ cells. Furthermore, adoptive transfer of Gr-1intCD11b+ cells reduced T cell infiltration, which improved graft survival. In conclusion, high-dose IFN-gamma in allograft areas is essential for development of Gr-1intCD11b+ MDSCs in corneal allografts, and subtle environmental changes in the early period of the allograft can result in a large difference in graft survival. PMID- 27370016 TI - Daily Pain, Physical Activity, and Home Fluid Intake in Pediatric Sickle Cell Disease. AB - Objectives: This study examined the temporal relationship between physical activity, fluid intake, and daily pain in children with sickle cell disease (SCD) with frequent pain. Methods: A total of 30 African American children ( M age = 13.9; 53% female; 76.3% type SS) who reported pain more than or equal to once every 2 weeks and their parents completed measures of pain and anxiety/depressive symptoms. Children then completed a daily pain diary and wore a physical activity Actiwatch for 14 days at home. Results: Contrary to physiological theory-based hypotheses, lower physical activity was associated with greater pain during the same day and the next day. Less pain was associated with greater physical activity the next day. There was no relationship between self-reported home fluid intake and daily pain ( p 's < .05). Conclusions: Results lend support for a complex bidirectional relationship between physical activity and daily pain in pediatric SCD, and identify physical activity as a target for future research. PMID- 27370017 TI - Different effects of isolation-rearing and neonatal MK-801 treatment on attentional modulations of prepulse inhibition of startle in rats. AB - RATIONAL: Prepulse inhibition (PPI) is suppression of the startle reflex by a weaker sensory stimulus (prepulse) preceding the startling stimulus. In people with schizophrenia, impairment of attentional modulation of PPI, but not impairment of baseline PPI, is correlated with symptom severity. In rats, both fear conditioning of prepulse and perceptually spatial separation between the conditioned prepulse and a noise masker enhance PPI (the paradigms of attentional modulation of PPI). OBJECTIVES: As a neurodevelopmental model of schizophrenia, isolation rearing impairs both baseline PPI and attentional modulations of PPI in rats. This study examined in Sprague-Dawley male rats whether neonatally blocking N-methyl-D-aspartate (NMDA) receptors specifically affects attentional modulations of PPI during adulthood. RESULTS: Both socially reared rats with neonatal exposure to the NMDA receptor antagonist MK-801 and isolation-reared rats exhibited augmented startle responses, but only isolation rearing impaired baseline PPI. Fear conditioning of the prepulse enhanced PPI in socially reared rats, but MK-801-treated rats lost the prepulse feature specificity. Perceptually spatial separation between the conditioned prepulse and a noise masker further enhanced PPI only in normally reared rats. Clozapine administration during adulthood generally weakened startle, enhanced baseline PPI in neonatally interrupted rats, and restored the fear conditioning-induced PPI enhancement in isolation-reared rats with a loss of the prepulse feature specificity. Clozapine administration also abolished both the perceptual separation-induced PPI enhancement in normally reared rats and the fear conditioning-induced PPI enhancement in MK-801-treated rats. CONCLUSIONS: Isolation rearing impairs both baseline PPI and attentional modulations of PPI, but neonatally disrupting NMDA receptor-mediated transmissions specifically impair attentional modulations of PPI. Clozapine has limited alleviating effects. PMID- 27370018 TI - Nicotinic acetylcholine receptor availability in cigarette smokers: effect of heavy caffeine or marijuana use. AB - RATIONALE: Upregulation of alpha4beta2* nicotinic acetylcholine receptors (nAChRs) is one of the most well-established effects of chronic cigarette smoking on the brain. Prior research by our group gave a preliminary indication that cigarette smokers with concomitant use of caffeine or marijuana have altered nAChR availability. OBJECTIVE: We sought to determine if smokers with heavy caffeine or marijuana use have different levels of alpha4beta2* nAChRs than smokers without these drug usages. METHODS: One hundred and one positron emission tomography (PET) scans, using the radiotracer 2-FA (a ligand for beta2* containing nAChRs), were obtained from four groups of males: non-smokers without heavy caffeine or marijuana use, smokers without heavy caffeine or marijuana use, smokers with heavy caffeine use (mean four coffee cups per day), and smokers with heavy marijuana use (mean 22 days of use per month). Total distribution volume (Vt/fp) was determined for the brainstem, prefrontal cortex, and thalamus, as a measure of nAChR availability. RESULTS: A significant between-group effect was found, resulting from the heavy caffeine and marijuana groups having the highest Vt/fp values (especially for the brainstem and prefrontal cortex), followed by smokers without such use, followed by non-smokers. Direct between-group comparisons revealed significant differences for Vt/fp values between the smoker groups with and without heavy caffeine or marijuana use. CONCLUSIONS: Smokers with heavy caffeine or marijuana use have higher alpha4beta2* nAChR availability than smokers without these drug usages. These findings are likely due to increased nicotine exposure but could also be due to an interaction on a cellular/molecular level. PMID- 27370021 TI - [Not Available]. PMID- 27370019 TI - Contingent and non-contingent recreational-like exposure to ethanol alters BDNF expression and signaling in the cortico-accumbal network differently. AB - RATIONALE: Although brain-derived neurotrophic factor (BDNF) is part of a homeostatic pathway involved in the development of alcohol dependence, it is not clear whether this is also true after recreational ethanol consumption. OBJECTIVES: We examined BDNF expression and signaling in the cortico-striatal network immediately and 24 h after either a single intravenous (i.v.) ethanol operant self-administration session or the last of 14 sessions. METHODS: To compare contingent and non-contingent ethanol exposure, we incorporated the "yoked control-operant paradigm" in which rats actively taking ethanol (S-Et) were paired with two yoked controls receiving passive infusions of ethanol (Y-Et) or saline. RESULTS: A single ethanol exposure transiently reduced BDNF mRNA levels in the medial prefrontal cortex (mPFC) of Y-Et. Immediately after the last of 14 sessions, mRNA and mature BDNF protein levels (mBDNF) were reduced in the mPFC in both S-Et and Y-Et while mBDNF expression was raised in the nucleus accumbens (NAc), suggesting enhanced anterograde transport from the mPFC. Conversely, 24 h later mBDNF expression and signaling were raised in the mPFC and NAc of S-Et rats but reduced in the NAc of Y-Et rats, with concomitant reduction of downstream signaling pathways. CONCLUSIONS: Our findings indicate that recreational-like i.v. doses of ethanol promote early changes in neurotrophin expression, depending on the length and modality of administration, the brain region investigated, and the presence of the drug. A rapid intervention targeting the BDNF system might be useful to prevent escalation to alcohol abuse. PMID- 27370020 TI - The effects of sex, estrous cycle, and social contact on cocaine and heroin self administration in rats. AB - RATIONALE: Preclinical studies indicate that gonadal hormones are important determinants of drug self-administration. To date, little is known about the influence of sex and estrous cycle on drug self-administration in ecologically relevant social contexts. OBJECTIVE: The objective of this study was to examine the role of sex and estrous cycle in a rat model during cocaine and heroin self administration with male-female and female-female social dyads. METHODS: Male and female virgin rats were trained to self-administer cocaine and heroin in operant conditioning chambers that permitted two rats to self-administer concurrently, but prevented physical contact. Experiment 1 examined cocaine self-administration on a progressive ratio schedule in male-female dyads. Experiments 2 and 3 examined heroin self-administration on a fixed ratio schedule in male-female dyads at constant and varying doses, respectively. Experiment 4 examined heroin self-administration in female-female dyads on a fixed ratio schedule. RESULTS: Cocaine-maintained breakpoints increased by ~17 % in females during estrus, but remained consistent in males. Heroin self-administration decreased by ~70 % during proestrus in females whether they were isolated, housed with males, or housed with females. Heroin self-administration was lower in males than females under some conditions and was not consistently associated with the responding of females. CONCLUSIONS: Cocaine and heroin self-administration is influenced by the estrous cycle in females when in the presence of a male partner. As a novel finding, these data illustrate that heroin self-administration is reduced in females during proestrus regardless of the social context tested. Finally, these data suggest that drug self-administration in males is only minimally influenced by the hormonal status of a female partner. PMID- 27370022 TI - [Not Available]. PMID- 27370023 TI - [Not Available]. PMID- 27370024 TI - [Not Available]. PMID- 27370025 TI - [Not Available]. PMID- 27370028 TI - [Not Available]. PMID- 27370026 TI - Validation of an automated assay for the measurement of cupric reducing antioxidant capacity in serum of dogs. AB - BACKGROUND: The objective of the present study was to optimize and validate an automated method to assess the total antioxidant capacity (TAC) in serum of dogs using the cupric reducing antioxidant capacity (CUPRAC) methodology (TACc) with bathocuproinedisulfonic acid disodium salt as chelating agent, evaluating also possible variations due to the use of two different automated analyzers. The method is based on the reduction of Cu(2+) into Cu(1+) by the action of the non enzymatic antioxidants that are present in the sample. RESULTS: Imprecision was low in both apparatus utilized, and the results were linear across serial Trolox and canine serum samples dilutions. Lipids did not interfere with the assay; however, hemolysis increased the TACc concentrations. When TACc concentrations were determined in ten healthy (control) dogs and in twelve dogs with inflammatory bowel disease (IBD), dogs with IBD had lower TACc concentrations when compared with the healthy dogs. CONCLUSIONS: The method validated in this paper is precise, simple, and fast and can be easily adapted to automated analyzers. PMID- 27370027 TI - In vitro performance and fracture resistance of CAD/CAM-fabricated implant supported molar crowns. AB - OBJECTIVES: The aim of this study is to investigate the performance and fracture resistance of different CAD/CAM ceramic and composite materials as implant- or tooth-supported single crowns with respect to the clinical procedure (screwed/bonded restoration). MATERIALS AND METHODS: One hundred twenty crowns were fabricated on implants or human molar teeth simulating (a) chairside procedure ([CHAIR] implant crown bonded to abutment), (b) labside procedure ([LAB] abutment and implant crown bonded in laboratory, screwed chairside), and (c) reference ([TOOTH] crowns luted on human teeth). Four materials were investigated: ZLS (zirconia-reinforced lithium silicate ceramic; Celtra Duo, Degudent: polished (P)/crystallized (C)), RB (resin-based composite; Cerasmart, GC), and RIC (resin-infiltrated ceramic; Enamic, Vita-Zahnfabrik). LiS (lithiumdisilicate; Emax CAD, Ivoclar-Vivadent) served as reference. Combined thermal cycling and mechanical loading (TCML) was performed simulating a 5-year clinical situation. Fracture force was determined. Data were statistically analyzed (Kolmogorov-Smirnov test, one-way ANOVA; post hoc Bonferroni, alpha = 0.05). RESULTS: One crown of ZLS_C[LAB] (1,200,000 cycles) and RB[CHAIR] (890 cycles) failed during TCML. Fracture values varied between 977.7 N(RB) and 3070.4 N(LiS)[CHAIR], 1130.6 N(RB) and 2998.1 N(LiS)[LAB], and 1802.4 N(ZLS) and 2664.3 N(LiS)[TOOTH]. Significantly (p < 0.003) different forces were found between the materials in all three groups. ZLS_C, RIC, and RB showed significantly (p < 0.014) different values for the individual groups. CONCLUSIONS: Partly ceramic and resin-based materials performed differently on implant or tooth abutments. The insertion of a screw channel reduced the stability for individual crown materials. Insertion of the screw channel should be performed carefully. CLINICAL RELEVANCE: All restorations were in a range where clinical application seems not restricted, but insertion of a screw channel might reduce stability of individual materials. PMID- 27370029 TI - [Not Available]. PMID- 27370030 TI - [Not Available]. PMID- 27370031 TI - [Not Available]. PMID- 27370033 TI - [Not Available]. PMID- 27370032 TI - [Not Available]. PMID- 27370034 TI - [Not Available]. PMID- 27370035 TI - [Not Available]. PMID- 27370036 TI - [Not Available]. PMID- 27370037 TI - [Not Available]. PMID- 27370038 TI - [Not Available]. PMID- 27370039 TI - [Not Available]. PMID- 27370040 TI - [Not Available]. PMID- 27370041 TI - [Not Available]. PMID- 27370043 TI - [Not Available]. PMID- 27370042 TI - [Not Available]. PMID- 27370044 TI - [Not Available]. PMID- 27370045 TI - [Not Available]. PMID- 27370047 TI - [Not Available]. PMID- 27370048 TI - [Not Available]. PMID- 27370046 TI - [Not Available]. PMID- 27370049 TI - [Not Available]. PMID- 27370050 TI - [Not Available]. PMID- 27370051 TI - [Not Available]. PMID- 27370052 TI - [Not Available]. PMID- 27370053 TI - [Not Available]. PMID- 27370054 TI - [Not Available]. PMID- 27370056 TI - [Not Available]. PMID- 27370055 TI - [Not Available]. PMID- 27370057 TI - [Not Available]. PMID- 27370058 TI - [MU-Opioid Receptor Gene (OPRM1) Polymorphisms A118G and C17T in Alcohol Dependence: A Turkish Sample]. AB - OBJECTIVES: Previous investigations on opioid system genetics have identified polymorphisms of the OPRM1 gene expressing MU-opioid receptors to be significantly associated with some features of alcohol dependence (AD). In the present study, we evaluated the relationship between single nucleotide polymorphisms (SNP) in the OPRM1 gene, A118G (rs1799971, Asn40Asp) and C17T (rs1799972, Arg6Val), and AD diagnosis, level of alcohol consumption, and AD severity in a Turkish sample. METHODS: 121 AD patients and 117 healthy male subjects were included in the study. OPRM1 A118G (N40D) and C17T (A6V) polymorphisms were evaluated using PCR - RFLP (polymerase chain reaction - restriction fragment length polymorphism) method. We evaluated the association between the presence of SNPs and AD diagnosis, family history of AD, AD severity evaluated via the Michigan Alcoholism Screening Test (MAST), the daily average and maximum quantity of alcohol consumed. RESULTS: There was no significant difference in OPRM1 A118G genotype frequencies between the AD and control groups. T allele frequency for the OPRM1 C17T SNP was very low (0.006) in the sample population. OPRM1 A118G SNP G118 allele carriers showed significantly higher levels of AD severity as indicated by the MAST. CONCLUSION: The OPRM1 G118 allele was significantly associated with more severe AD in the Turkish population. Similar to other European populations, the frequency of the OPRM1 T17 allele was very low. PMID- 27370059 TI - [Effect of Topiramate on Drug Associated Weight Gain of Patients with Schizophrenia and Bipolar I Disorders: A Dose Ranging Randomized Trial]. AB - INTRODUCTION: The aim of this study was to explore the probable prophylactic effects and evaluate different doses of topiramate on body weight in patients treated with olanzapine. MATERIALS AND METHODS: This was a 12 week, double-blind, placebo-controlled clinical trial (Iranian Clinical Trial Registration Code: 201402085280N15) to assess the preventative effects and estimate the optimal dosage of topiramate in drug-induced weight gain. Sixty eight patients aged 18 to 60 that were hospitalized and treated with olanzapine between 2009-2011due to the onset of an acute episode of schizophrenia or a manic episode of bipolar I disorder were selected in Mashhad, the second largest city in the northeast of Iran. Patients were randomly assigned to 4 groups, including 1- placebo; 2- 50 mg/day; 3- 100 mg/day; and 4- 200 mg/day topiramate. Two psychiatrists assigned participants to an intervention group and followed up the treatment process. Raters weighed patients at baseline and also at weeks 1, 2, 4, 6, 8, and 12, respectively. Waist and wrist circumferences were measured at baseline and weeks 4, 8, and 12. Body weight, BMI, wrist, and waist circumference changes were outcome measures of the study. Collected data were analyzed by ANOVA, post hoc Tukey test, Kruskal-Wallis, Mann-Whitney U, and Cohen's d with SPSS version 14. A p-value of less than 0.05 was considered significant. RESULTS: All outcome measures were significantly less than the placebo group compared to the topiramate groups at the end of the fourth week and continued to twelfth week. Nevertheless, there was no statistically significant difference in the measures of any of the topiramate groups with each other at any interval. CONCLUSION: All doses of 50, 100, and 200mg were shown effective in preventing olanzapine-related obesity in schizophrenic and/or bipolar patients. PMID- 27370060 TI - [The Relationship between Violence and Clinical Features, Insight and Cognitive Functions in Patients with Schizophrenia]. AB - OBJECTIVE: We aimed to investigate the predictive factors of violent behavior in schizophrenia and the relationship between violent behavior and insight and cognitive functions in this study. METHOD: 68 patients diagnosed with schizophrenia were separated into two groups; with a history of violent behavior (n = 30) and without (n = 38). Both group swere administered the Positiveand Negative Syndrome Scale (PANSS), Buss-Perry Aggression Questionnaire, Schedule for Assessing the Three Components of Insight, California Verbal Learning Test (CVLT), Trail Making Test, Wisconsin Card Sorting Test, and Stroop Test. RESULTS: Male gender, the number of hospitalizations, incompliance with the treatment, alcohol and substance abuse, the number of suicide attempts, the mean score of PANSS positive symptoms, PANSS general symptoms and PANSS total were significantly higher in patients with schizophrenia with a history of violent behavior, compared to non-violent group. Long delayed response subsection of CVLT mean score was lower in patients with violent behavior. Incompliance with the treatment (OR:5.927, p=0.041), alcohol and substance abuse (OR:21.089, p=0.000), and PANSS total score (OR:1.053, p=0.011)were identified as predictive factors of violent behavior in patients with schizophrenia. CONCLUSION: Lack of insight and executive function impairment are the core symptoms of schizophrenia and not seems to be associated with violent behavior in patients with schizophrenia. Impairment of memory may be associated with violent behavior in patients with schizophrenia. Incompliance with treatment, alcohol and substance abuse, and the severity of positive symptoms are important factors in predicting violence behavior in patients with schizophrenia. PMID- 27370061 TI - [Examination of the Metacognitive Model of Depression in a Turkish University Student Sample]. AB - AIM: The aim of the present study is to test the metacognitive model of depression in a Turkish sample using structural equation modeling. METHOD: A total of 305 university students participated in this study. The data concerning the levels of rumination, positive beliefs about rumination (positive beliefs), negative beliefs about uncontrollability and harm of rumination (negative beliefs 1), negative beliefs about interpersonal and social consequences of rumination (negative beliefs-2), lack of cognitive confidence, and depression was collected using a web-survey method. RESULTS: The results indicated a number of necessary modifications that are needed in order to obtain a good fitting model for the data. The implementation of these theoretically consistent modifications resulted in a good fitting modified model. Accordingly, positive beliefs predicted depressive symptoms by means of rumination, negative beliefs-1, and negative beliefs-2. Negative beliefs-1 and negative beliefs-2 partially mediated the relationship between rumination and depression as well. In addition, the whole process with regard to the elucidation of depressive symptomatology significantly explained the change in the level of cognitive confidence. CONCLUSION: Overall, the findings obtained from the present study support the validity of the basic components of the metacognitive model of depression in a Turkish sample. PMID- 27370062 TI - [The Effectiveness of Cognitive Behavioral Therapy, Medication, or Combined Treatment For Child Hood Anxiety Disorders]. AB - OBJECTIVE: The aims of this study were to evaluate the effectiveness of the Fear Hunter cognitive behavioral therapy program, which was developed for the treatment of childhood anxiety disorders, and to compare its effectiveness with standard medication treatment. METHOD: A total of 46 participants (aged 8 to 12) that applied to the Ege University, Faculty of Medicine, Child and Adolescent Psychiatry clinic and had a diagnosis of anxiety disorder were recruited for the study. The participants were randomly assigned to cognitive behavioral therapy (CBT), standard drug treatment (ST), or combined treatment (CBT+ ST) groups according to the order of application. Subjects were evaluated using pretest, posttest and 3 months follow-up measurements. The participants were assessed by the researcher using The Screen for Child Anxiety Related Emotional Disorders (SCARED), The Children's Negative Cognitive Errors Questionnaire (CNCEQ), Health Related Quality of Life in Children (Kid-KINDL), and Children's Depression Inventory (CDI). RESULTS: The results of repeated measures ANOVA showed that, although general anxiety scores of all treatment conditions significantly decreased at posttest and follow up, a combination of two therapies (CBT+ST) had a significantly superior response rate. Moreover, all treatment conditions including CBT (CBT+ST and CBT) were superior to ST in terms of negative cognitive errors, quality of life, and depression. CONCLUSION: It is thought that The Fear Hunter Therapy Program is an effective treatment technique because; it provides significant improvement in the primary and secondary symptoms (e.g. quality of life, depression, negative automatic thoughts) of childhood anxiety disorders. PMID- 27370063 TI - [The Assessment of the Auditory Hallucinations and Delusions: The Reliability and the Validity of Turkish Version of the Psychotic Symptom Rating Scales (PSYRATS)]. AB - OBJECTIVE: The aim of this study is to examine the reliability and validity of Turkish version of PSYRATS Auditory Hallucinations Scales (AHS) and Delusion Scales (DS). METHOD: 85 schizophrenic outpatients or inpatients aged between 18 and 65 years were the subjects of this study. The patients diagnosed by using the DSM-IV-TR and who have psychosis with alcohol or drug dependence, organic, mental and physical deficit were not included to the study. PSYRATS scales were translated and corrected by the authors. PSYRATS were applied for two times per week to 57 patients to determine test-retest reliability. 85 patients were applied PANSS and 71 of them were applied SAPS to determine the concurrent validity. RESULTS: Cronbach Alpha coefficient was calculated as .79 for AHS and .80 for DS. For the AHS each item correlated between .59 and .98; for the DS each correlated between .66 and .93. For the test-retest reliability, item correlation coefficient of AHS is determined between .68 and .89, DS is .61 and .76 (p<0.01). Supporting the concurrent validity, a significant correlation was found between PANSS and SAPS (p<0.01). Three factor groups for AHS and also DH were revealed and examined more than 90 % of the variance. The results were supported by the original study findings. CONCLUSION: PSYRATS Auditory Hallucination and Delusion Scales were found to be reliable and valid measures to assess the dimensions of psychotic symptoms in Turkish schizophrenia patients. PMID- 27370064 TI - [Digital Game Addiction Among Adolescents and Younger Adults: A Current Overview]. AB - The games that adolescents and young people used to play in the play grounds and on the streets have been replaced in recent years with cyber games played in front of the computer on the internet or in game arcades. This changing culture has particularly brought up the concept of "digital game addiction", a condition that stems from the steadily growing passion for digital games and their excessived and uncontrolled usage among adolescents and young people. Game addiction in the psychiatry literature has been described as an impulse control disorder characterized by the symptoms such as "the inability to control the time spent on game-playing", "a loss of interest in other activities", "continuing to play despite the adverse effects" and "feeling psychologically deprived when not being able to play"."Although digital game addiction has not been accepted by psychiatric authorities as a psychiatric disorder yet, the increasing psychiatry referrals due to the problems accompanying this disorder, the efforts of families to seek support and solutions, the evidence that similarities with other types of addiction have been revealed by researchers, as well as the current prevalence rates are all factors that suggest the existence of important of the examination of issue. Despite the discussions about the digital game addiction, the literature on the subject is increasing. This article offers an overview of digital game-playing behavior in the light of current literature, seeking to share its findings with health care professionals. PMID- 27370065 TI - [Hoarding Behaviour in Three Different Types of Dementia Cases]. AB - INTRODUCTION: Hoarding behaviour, which is generally defined as collecting and keeping unnecessary, cheap objects or things that can not be used, is more common in elderly than young people. The prevelance of hoarding behaviour in dementia was reported as 22%. In this paper, three different types of dementia cases are presented in order to emphasize the clinical awareness for hoarding disorder, which is common in the elderly, especially those with dementia. CASES: The first case is a patient with a diagnosis of frontotemporal dementia who was collecting old things before the appearance of bahavioural changes like verbal and physical agitation. The second one is a patient who was admitted with complaints of forgetting, diagnosed as having Alzheimer's Disease and presented with paper hoarding behavior in his clinical follow-up. The last patient was presented with visual hallucinations, forgetting, collecting old things and depressive symptoms. He received a diagnosis of Lewy body dementia. DISCUSSION: It is prominent that all three different dementia cases hoarding behavior at early stages of dementia. It should be kept in mind that hoarding behavior which begins at late life might be a sign of dementia or it might appear in the dementia process. PMID- 27370066 TI - [Evaluation of a Neuropsychiatric Disorder: From PANDAS to PANS and CANS]. AB - PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) syndrome is a disorder seen before adolescence that possesses an abrupt onset of obsessive-compulsive disorder symptoms and/or tics. Swedo and colleagues defined this disorder in 1998 as a syndrome related to Group A streptoccoccus (GAS) infection with neurological issues, such as motor hyperactivation and choreiform movements. The progress of the disorder may be described as wax-and-waning, apart from abrupt onset, and this relapse and remission course is associated with exacerbating infections, according to the creators of PANDAS syndrome. Ruling out of Rheumatoid Fever and Sydenham's Chorea was a necessity for making a proper diagnosis. Since the recognition of this syndrome, clinicians encountered many children who could not fulfill all 5 criteria, which must be met for PANDAS diagnosis. In addition, due to literature showing failure and lack of strong evidence of a major role of GAS, the newly defined categories PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) and CANS (Childhood Acute Neuropsychiatric Syndrome) were created to encompass those of "almost met" non-PANDAS cases. PANS and CANS include concurrent significant psychiatric symptoms with abrupt onset of OCD symptoms and/or tics but do not require identification of any infection agent, immune dysfunction, or enviromental precipitants. In this paper, we aimed to discuss PANS/ CANS, alterations of PANDAS, and diagnoses in which "almost met" PANDAS patients should be classified on the basis of a case who developed an abrupt onset of anxiety, obsessions, and vocal tics. PMID- 27370067 TI - [Editorial]. PMID- 27370068 TI - Iodine Status and Prevalence of Thyroid Disorders After Introduction of Mandatory Universal Salt Iodization for 16 Years in China: A Cross-Sectional Study in 10 Cities. AB - BACKGROUND: The goal of eliminating iodine deficiency worldwide was successfully achieved in China after the implementation of a mandatory universal salt iodization program for the last 16 years. Thus, China has been assessed as a country with more than adequate iodine levels. This survey aimed to investigate the current iodine status in China and the effects of an increased iodine intake on the spectrum and prevalence of thyroid disorders. METHODS: A total of 15,008 adult subjects from 10 cities in eastern and central China were investigated. Serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), and urine iodine concentration (UIC) were measured, and an ultrasonography of the thyroid was performed in all subjects. Free thyroxine (fT4) and free triiodothyronine (fT3) levels were only measured if the serum TSH was outside the normal range. RESULTS: The median UIC values were 197 MUg/L in school-age children (SAC) and 205 MUg/L in a cohort population. Six cities were classified as regions with adequate iodine intake (AII), and four cities as regions with more than adequate iodine intake (MTAII), according to median SAC UIC. The prevalence of clinical hypothyroidism, subclinical hypothyroidism, and positive thyroid antibodies was significantly higher in MTAII cities than it was in AII cities. Moreover, the prevalence of clinical hyperthyroidism (1.1% vs. 0.8%, p = 0.033) and Graves' disease (0.8% vs. 0.5%, p = 0.019) also significantly increased in MTAII cities. Compared with a five-year prospective study conducted in 1999, the prevalence of goiter significantly decreased (2.9% vs. 5.02%, p = 0.001), but there was a significant increase in thyroid nodules (12.8% vs. 2.78%, p = 0.001). The prevalence of subclinical hypothyroidism (16.7% vs. 3.22%), positive TPOAb (11.5% vs. 9.81%), and positive TgAb (12.6% vs. 9.09%) significantly increased, while no changes were seen in clinical hyperthyroidism, subclinical hyperthyroidism, or Graves' disease. CONCLUSION: The goal of eliminating iodine deficiency has been successfully achieved in China. However, the prevalence and spectrum of thyroid disorders has increased, reflecting possible adverse effects of increased iodine intake. PMID- 27370071 TI - Introduction to Volume 8, Issue 3 of topiCS. PMID- 27370069 TI - Right Ventricular Myocardial Stiffness in Experimental Pulmonary Arterial Hypertension: Relative Contribution of Fibrosis and Myofibril Stiffness. AB - BACKGROUND: The purpose of this study was to determine the relative contribution of fibrosis-mediated and myofibril-mediated stiffness in rats with mild and severe right ventricular (RV) dysfunction. METHODS AND RESULTS: By performing pulmonary artery banding of different diameters for 7 weeks, mild RV dysfunction (O=0.6 mm) and severe RV dysfunction (O=0.5 mm) were induced in rats. The relative contribution of fibrosis- and myofibril-mediated RV stiffness was determined in RV trabecular strips. Total myocardial stiffness was increased in trabeculae from both mild and severe RV dysfunction in comparison to controls. In severe RV dysfunction, increased RV myocardial stiffness was explained by both increased fibrosis-mediated stiffness and increased myofibril-mediated stiffness, whereas in mild RV dysfunction, only myofibril-mediated stiffness was increased in comparison to control. Histological analyses revealed that RV fibrosis gradually increased with severity of RV dysfunction, whereas the ratio of collagen I/III expression was only elevated in severe RV dysfunction. Stiffness measurements in single membrane-permeabilized RV cardiomyocytes demonstrated a gradual increase in RV myofibril stiffness, which was partially restored by protein kinase A in both mild and severe RV dysfunction. Increased expression of compliant titin isoforms was observed only in mild RV dysfunction, whereas titin phosphorylation was reduced in both mild and severe RV dysfunction. CONCLUSIONS: RV myocardial stiffness is increased in rats with mild and severe RV dysfunction. In mild RV dysfunction, stiffness is mainly determined by increased myofibril stiffness. In severe RV dysfunction, both myofibril- and fibrosis-mediated stiffness contribute to increased RV myocardial stiffness. PMID- 27370070 TI - Evaluation of an Expert System for the Generation of Speech and Language Therapy Plans. AB - BACKGROUND: Speech and language pathologists (SLPs) deal with a wide spectrum of disorders, arising from many different conditions, that affect voice, speech, language, and swallowing capabilities in different ways. Therefore, the outcomes of Speech and Language Therapy (SLT) are highly dependent on the accurate, consistent, and complete design of personalized therapy plans. However, SLPs often have very limited time to work with their patients and to browse the large (and growing) catalogue of activities and specific exercises that can be put into therapy plans. As a consequence, many plans are suboptimal and fail to address the specific needs of each patient. OBJECTIVE: We aimed to evaluate an expert system that automatically generates plans for speech and language therapy, containing semiannual activities in the five areas of hearing, oral structure and function, linguistic formulation, expressive language and articulation, and receptive language. The goal was to assess whether the expert system speeds up the SLPs' work and leads to more accurate, consistent, and complete therapy plans for their patients. METHODS: We examined the evaluation results of the SPELTA expert system in supporting the decision making of 4 SLPs treating children in three special education institutions in Ecuador. The expert system was first trained with data from 117 cases, including medical data; diagnosis for voice, speech, language and swallowing capabilities; and therapy plans created manually by the SLPs. It was then used to automatically generate new therapy plans for 13 new patients. The SLPs were finally asked to evaluate the accuracy, consistency, and completeness of those plans. A four-fold cross-validation experiment was also run on the original corpus of 117 cases in order to assess the significance of the results. RESULTS: The evaluation showed that 87% of the outputs provided by the SPELTA expert system were considered valid therapy plans for the different areas. The SLPs rated the overall accuracy, consistency, and completeness of the proposed activities with 4.65, 4.6, and 4.6 points (to a maximum of 5), respectively. The ratings for the subplans generated for the areas of hearing, oral structure and function, and linguistic formulation were nearly perfect, whereas the subplans for expressive language and articulation and for receptive language failed to deal properly with some of the subject cases. Overall, the SLPs indicated that over 90% of the subplans generated automatically were "better than" or "as good as" what the SLPs would have created manually if given the average time they can devote to the task. The cross-validation experiment yielded very similar results. CONCLUSIONS: The results show that the SPELTA expert system provides valuable input for SLPs to design proper therapy plans for their patients, in a shorter time and considering a larger set of activities than proceeding manually. The algorithms worked well even in the presence of a sparse corpus, and the evidence suggests that the system will become more reliable as it is trained with more subjects. PMID- 27370072 TI - A Recursive Partitioning Method for the Prediction of Preference Rankings Based Upon Kemeny Distances. AB - Preference rankings usually depend on the characteristics of both the individuals judging a set of objects and the objects being judged. This topic has been handled in the literature with log-linear representations of the generalized Bradley-Terry model and, recently, with distance-based tree models for rankings. A limitation of these approaches is that they only work with full rankings or with a pre-specified pattern governing the presence of ties, and/or they are based on quite strict distributional assumptions. To overcome these limitations, we propose a new prediction tree method for ranking data that is totally distribution-free. It combines Kemeny's axiomatic approach to define a unique distance between rankings with the CART approach to find a stable prediction tree. Furthermore, our method is not limited by any particular design of the pattern of ties. The method is evaluated in an extensive full-factorial Monte Carlo study with a new simulation design. PMID- 27370074 TI - [Not Available]. PMID- 27370075 TI - [Not Available]. PMID- 27370073 TI - The Speaking Voice in the General Population: Normative Data and Associations to Sociodemographic and Lifestyle Factors. AB - OBJECTIVES: Normative data concerning the speaking voice in the general population were gathered with the aim to establish standard values for clinical diagnostics. Associations between the speaking voice and sociodemographic factors were examined. STUDY DESIGN: This is a prospective cross-sectional population based study. METHODS: Speaking voice profiles were measured for 2472 (1154 male and 1318 female) participants between the ages of 40 and 79 years, using four speaking voice intensity levels: softest speaking voice (I), conversational voice (II), classroom voice (III), and shouting voice (IV). Smoking status and socioeconomic status were assessed. Data were analyzed using multivariate regression. RESULTS: The mean voice frequencies were 111.8 Hz for male and 161.3 Hz for female participants (I), 111.9 Hz for male and 168.5 Hz for female participants (II), 130.2 Hz for male and 198.0 Hz for female participants (III), and 175.5 Hz for male and 246.2 Hz for female participants (IV). Frequencies increased significantly with age for male but not for female participants. Sound pressure levels rose significantly with age at intensity levels I-III for both sexes, but decreased at intensity level IV. Frequencies and sound pressure levels were similar between nonsmokers and former smokers. Current smokers showed significantly lower frequencies as opposed to non- and former smokers. Speaking voice range and dynamics increased with higher socioeconomic status. CONCLUSIONS: The data are suitable as age-adjusted normative values for clinical measurement of the speaking voice. The mean fundamental speaking voice frequency of female participants was six to seven semitones lower than previously described. PMID- 27370076 TI - [Not Available]. PMID- 27370077 TI - [Not Available]. PMID- 27370078 TI - [Not Available]. PMID- 27370080 TI - [Not Available]. PMID- 27370079 TI - [Not Available]. PMID- 27370081 TI - [Not Available]. PMID- 27370083 TI - [Not Available]. PMID- 27370082 TI - [Not Available]. PMID- 27370084 TI - [Not Available]. PMID- 27370086 TI - [Not Available]. PMID- 27370085 TI - [Not Available]. PMID- 27370087 TI - [Not Available]. PMID- 27370088 TI - [Not Available]. PMID- 27370089 TI - [Not Available]. PMID- 27370090 TI - [Not Available]. PMID- 27370091 TI - [Not Available]. PMID- 27370093 TI - [Not Available]. PMID- 27370092 TI - [Not Available]. PMID- 27370094 TI - [Not Available]. PMID- 27370095 TI - [Not Available]. PMID- 27370096 TI - Importance of Managing for Personal Benefits, Hedonic and Utilitarian Motivations, and Place Attachment at an Urban Natural Setting. AB - Research on antecedents of place attachment suggests that the special bonds people form with nature are influenced by a number of variables. This study examines associations between the perceived importance of managing for personal benefits, motivations, and place attachment among outdoor recreationists at an urban natural setting. Motivation was conceptualized as two-dimensional (Hedonic and Utilitarian) borrowed from the retail and consumer marketing field and previously unused in a natural resource recreation context. Hedonic and utilitarian motivations represent the experiential and functional dimensions of motivation, respectively. Relationships between the noted variables were examined through structural equation modeling. Data from an onsite survey of 219 users indicated that it was important the resource be managed to provide greater freedom from urban living as well as improved mental well-being. Furthermore, respondents exhibited moderate levels of hedonic and utilitarian motivations as well as attachment to the resource. The structural equation analysis resulted in a good fitting model with several significant relationships emerging. Among these, the perceived importance of managing for personal benefits positively influenced hedonic and utilitarian motivations. In addition, hedonic motivations positively influenced place attachment development, whereas utilitarian motivations did not. Implications of these findings are discussed. PMID- 27370097 TI - Hypouricemic effect of allopurinol are improved by Pallidifloside D based on the uric acid metabolism enzymes PRPS, HGPRT and PRPPAT. AB - Allopurinol is a commonly used medication to treat hyperuricemia and its complications. Pallidifloside D, a saponin glycoside constituent from the total saponins of Smilax riparia, had been proved to enhanced hypouricemic effect of allopurinol based on uric acid metabolism enzyme XOD. In this study, we evaluated whether Pallidifloside D (5mg/kg) enhanced hypouricemic effect of allopurinol (5mg/kg) related to others uric acid metabolism enzymes such as PRPS, HGPRT and PRPPAT. We found that, compared with allopurinol alone, the combination of allopurinol and Pallidifloside D significantly up-regulated HGPRT mRNA expression and down-regulated the mRNA expression of PRPS and PRPPAT in PC12 cells (all P<0.01). These results strongly suggest that hypouricemic effect of allopurinol are improved by Pallidifloside D via numerous mechanisms and our data may have a potential value in clinical practice in the treatment of gout and other hyperuricemic conditions. PMID- 27370098 TI - Quantitatively metabolic profiles of salvianolic acids in rats after gastric administration of Salvia miltiorrhiza extract. AB - Salvianolic acids, the well-known active components in Salvia miltiorrhiza, have been shown to possess markedly pharmacological activities. However, due to the complex in vivo course after administration, the pharmacologically active forms are still poorly understood. In present study, we evaluated the stability of eight major salvianolic acids from Danshen extract under different chemical and physiological conditions. We also quantitatively explained the absorption, metabolism and excretion of these salvianolic acids in rats after gastric administration, which was carried out by simultaneously determining the amounts of salvianolic acids and their metabolites in the rat gastrointestinal contents, gastrointestinal mucosa, plasma, bile and urine. We found that: 1) protocatechuic aldehyde (PAL) was much stable whether in acidic environment (pH4.0) or in alkaline environment (pH8.0), while other salvianolic acids were stable in acidic environment and instable in alkaline environment; 2) PAL, salvianoli acid A (SAA) and salvianolic acid B (SAB) were instable whether in rat stomach or in small intestine, while other salvianolic acids were stable in rat stomach and instable in small intestine; 3) after gastric-administration, except PAL and Danshensu (DSS), other phenolic acids would be metabolized into DSS and caffeic acid (CA) in the rat gastrointestinal tract before absorption, and only free and glucuronidated PAL, CA and DSS were detected in rat plasma, bile and urine. In conclusion, it was the free and glucuronidated PAL, CA and DSS rather than the prototypes of other salvianolic acids that were present in plasma with considerable concentrations after gastric-administration. PMID- 27370099 TI - Asperosaponin VI promotes progesterone receptor expression in decidual cells via the notch signaling pathway. AB - Recurrent spontaneous abortion (RSA) is a common clinical condition, but its reasons remain unknown in 37-79% of the affected women. The steroid hormone progesterone (P4) is an integral mediator of early pregnancy events, exerting its effects via the progesterone receptor (PR). Dipsaci Radix (DR) has long been used for treating gynecological diseases in Chinese medicine, while its molecular mechanisms and active ingredients are still unclear. We report here the progesterone-like effects of the alcohol extraction and Asperosaponin VI from DR in primary decidual cells and HeLa cell line. We first determined the safe concentration of Asperosaponin VI in the cells with MTT assay and then found by using dual luciferase reporter and Western blotting that Asperosaponin VI significantly increased PR expression. Moreover, we explored the mechanisms of action of the DR extracts and Asperosaponin VI, and the results showed that they could activate Notch signaling, suggesting that they may function by promoting decidualization. PMID- 27370100 TI - Baicalein modulates stress-resistance and life span in C. elegans via SKN-1 but not DAF-16. AB - The flavonoid baicalein has been demonstrated to be an activator of the transcription factor Nrf2 in mammalian cell lines. We show that it further modulates the Nrf2 homolog SKN-1 in Caenorhabditis elegans and by this pathway mediates beneficial effects in the nematode: baicalein enhances the resistance of C. elegans against lethal thermal and sodium arsenite stress and dose-dependently prolongs the life span of the nematode. Using RNA interference against SKN-1 we were able to show that the induction of longevity and the enhanced stress resistance were dependent on this transcription factor. DAF-16 (homolog to mammalian FOXO) is another pivotal aging-related transcription factor in the nematode. We demonstrate that DAF-16 does not participate in the beneficial effects of baicalein: since baicalein causes no increase in the nuclear translocation of DAF-16 (DAF-16::GFP expressing strain, incubation time: 1h) and it still induces longevity even in a DAF-16 loss-of-function strain, we conclude, that baicalein increases stress-resistance and life span in C. elegans via SKN-1 but not DAF-16. PMID- 27370101 TI - Butenolide derivatives from the plant endophytic fungus Aspergillus terreus. AB - Three new butenolides containing 5-hydroxyfuran-2(5H)-one core, asperteretal A (1), asperteretal B (2), and asperteretal C (3), together with seven known butenolides (4-10), were obtained from an endophytic fungus Aspergillus terreus PR-P-2 isolated from the plant Camellia sinensis var. assamica. The structures of compounds 1-3 were elucidated on the basis of detailed spectroscopic analysis including UV, IR, HRESIMS, 1D and 2D NMR, and ECD spectra. Compounds 1, 3, 5 and 6-8 showed potent inhibitory effects on NO production in RAW 264.7 lipopolysaccharide-induced macrophages, and compounds 5 and 8 also exhibited moderate cytotoxicity against HL-60 cell line. PMID- 27370102 TI - Does the method of botulinum neurotoxin injection for limb spasticity affect outcomes? A systematic review. AB - OBJECTIVE: To systematically review randomized controlled trials of botulinum neurotoxin for limb spasticity to determine whether different injection techniques affect spasticity outcomes. METHODS: MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials electronic databases were searched for English language human randomized controlled trials from 1990 to 13 May 2016. Studies were assessed in duplicate for data extraction and risk of bias using the Physiotherapy Evidence Database scale and graded according to Sackett's levels of evidence. RESULTS: Nine of 347 studies screened met selection criteria. Four categories of botulinum neurotoxin injection techniques were identified: (1) injection localization technique; (2) injection site selection; (3) injectate volume; (4) injection volume and site selection. There is level 1 evidence that: ultrasound, electromyography, and electrostimulation are superior to manual needle placement; endplate injections improve outcomes vs. multisite quadrant injections; motor point injections are equivalent to multisite injections; high volume injections are similar to low volume injections; and high volume injections distant from the endplate are more efficacious than low volumes closer to the endplate. CONCLUSION: Level 1 evidence exists for differences in treatment outcomes using specific botulinum neurotoxin injection techniques. Findings are based on single studies that require independent replication and further study. PMID- 27370103 TI - Recent advances in the management of atypical meningiomas. AB - Based on the 2007 WHO classification, the proportion of atypical meningiomas has steeply increased. Complete resection is usually considered curative, however, the recurrence rate remains high. The treatment of more aggressive meningiomas remains problematic. We performed a literature review via the PubMed database with specific attention to radiological, pathological, genetic and molecular aspects particular to WHO grade II meningiomas and current therapeutic strategies. We also reviewed the role of surgery and summarized the results of the principal studies dealing with adjuvant strategies based on the most recent evidence. Adjuvant radiotherapy, administered as stereotactic radiosurgery or conventional external beam irradiation, should be strongly considered in selected cases. Limited data exist regarding the role of hormonal treatment or chemotherapy as adjunct therapy. A target therapy modulating the altered molecular balance may be the key to revolutionize the prognosis of these patients. PMID- 27370104 TI - Erratum to: Kidney Injury and Alterations of Inflammatory Cytokine Expressions in Mice Following Long-Term Exposure to Cerium Chloride. PMID- 27370105 TI - Corrigendum. PMID- 27370107 TI - Wisdom and tenacity: Our inseparable companions on this long and hard road. PMID- 27370106 TI - Complexity and multi-factoriality of Trypanosoma cruzi sylvatic cycle in coatis, Nasua nasua (Procyonidae), and triatomine bugs in the Brazilian Pantanal. AB - BACKGROUND: Trypanosoma cruzi is dispersed in nature through many transmission mechanisms among a high diversity of vectors and mammalian species, representing particular behaviors and habitats. Thus, each locality has a unique set of conditions underlying the maintenance of this parasite in the wild. The aim of the present study was to evaluate the life-cycle of T. cruzi in free-ranging coatis from the central region of the Brazilian Pantanal using a multi-factorial approach. METHODS: Three methodological blocks were used in the present study: (i) We evaluated T. cruzi infection using serological (ELISA) and parasitological (hemoculture) tests in free-ranging coatis captured from October 2010 to March 2012. In addition, we characterized T. cruzi isolates as DTUs (Discrete Typing Units); (ii) We evaluated Trypanosoma infection in species of Triatoma and Rhodnius inhabiting coati arboreal nests from May to September 2012 using parasitological and molecular assays; and (iii) We analyzed a set of longitudinal data (from 2005 to 2012) concerning the effects of T. cruzi infection on this coati population. Herein, we investigated whether seasonality, host sex, and host age influence T. cruzi prevalence and patterns of infection. RESULTS: The 2010 2012 period presented high seroprevalence on coatis (72.0 % ELISA) and a high percentage of individuals with infectivity competence (20.5 % positive hemoculture). All isolates presented TcI band patterns, occurring in single (n = 3) and mixed infections (1 TcI/T. rangeli; 4 with undefined characterization). Both male and female individuals presented the same transmission potential, expressed as positive hemoculture, which was only detected in the summer. However, overall, the data (2005-2012) highlighted the importance of females for T. cruzi maintenance in the winter. Moreover, twenty-three (67.6 %) bugs from five coati nests (71.4 %) were infected with flagellated forms. Seventeen samples were characterized as T. cruzi (TcI and TcIII genotypes). CONCLUSION: In the Pantanal region, T. cruzi is transmitted in a complex, multifactorial, dynamic and non-linear transmission web. The coati nests might be inserted in this web, acting as important transmission foci at the arboreal stratum to different mammal species with arboreal or scansorial behavior. PMID- 27370108 TI - You are not alone! PMID- 27370109 TI - Microsecond Rearrangements of Hydrophobic Clusters in an Initially Collapsed Globule Prime Structure Formation during the Folding of a Small Protein. AB - Determining how polypeptide chain collapse initiates structure formation during protein folding is a long standing goal. It has been challenging to characterize experimentally the dynamics of the polypeptide chain, which lead to the formation of a compact kinetic molten globule (MG) in about a millisecond. In this study, the sub-millisecond events that occur early during the folding of monellin from the guanidine hydrochloride-unfolded state have been characterized using multiple fluorescence and fluorescence resonance energy transfer probes. The kinetic MG is shown to form in a noncooperative manner from the unfolded (U) state as a result of at least three different processes happening during the first millisecond of folding. Initial chain compaction completes within the first 37MUs, and further compaction occurs only after structure formation commences at a few milliseconds of folding. The transient nonnative and native-like hydrophobic clusters with side chains of certain residues buried form during the initial chain collapse and the nonnative clusters quickly disassemble. Subsequently, partial chain desolvation occurs, leading to the formation of a kinetic MG. The initial chain compaction and subsequent chain rearrangement appear to be barrierless processes. The two structural rearrangements within the collapsed globule appear to prime the protein for the actual folding transition. PMID- 27370110 TI - In vitro determination of the solubility limit of cholesterol in phospholipid bilayers. AB - Cholesterol has limited solubility in phospholipid bilayers. The solubility limit is strongly dependent on the nature of the lipid with which the cholesterol is mixed while properties of the crystals formed can be modified by phospholipid cholesterol interactions. In this review we summarize the various methods that have been developed to prepare hydrated mixtures of cholesterol and phospholipid. We point out some of the factors that determine the form adopted when cholesterol crystallizes in such mixtures, i.e. two- or three-dimensional, monohydrate or anhydrous. These differences can greatly affect the ability to experimentally detect the presence of these crystals in a membrane. Several methods for detecting cholesterol crystals are discussed and compared including DSC, X-ray and GIXRD diffraction methods, NMR and EPR spectroscopy. The importance of the history of the sample in determining the amount and nature of the cholesterol crystals formed is emphasized. PMID- 27370111 TI - Introduction to the Special Issue on "Properties and Functions of Cholesterol". PMID- 27370112 TI - Within the next five years, adaptive hypofractionation will become the most common form of radiotherapy. PMID- 27370113 TI - An efficient computational approach to model statistical correlations in photon counting x-ray detectors. AB - PURPOSE: To introduce and evaluate an increment matrix approach (IMA) describing the signal statistics of energy-selective photon counting detectors including spatial-spectral correlations between energy bins of neighboring detector pixels. The importance of the occurring correlations for image-based material decomposition is studied. METHODS: An IMA describing the counter increase patterns in a photon counting detector is proposed. This IMA has the potential to decrease the number of required random numbers compared to Monte Carlo simulations by pursuing an approach based on convolutions. To validate and demonstrate the IMA, an approximate semirealistic detector model is provided, simulating a photon counting detector in a simplified manner, e.g., by neglecting count rate-dependent effects. In this way, the spatial-spectral correlations on the detector level are obtained and fed into the IMA. The importance of these correlations in reconstructed energy bin images and the corresponding detector performance in image-based material decomposition is evaluated using a statistically optimal decomposition algorithm. RESULTS: The results of IMA together with the semirealistic detector model were compared to other models and measurements using the spectral response and the energy bin sensitivity, finding a good agreement. Correlations between the different reconstructed energy bin images could be observed, and turned out to be of weak nature. These correlations were found to be not relevant in image-based material decomposition. An even simpler simulation procedure based on the energy bin sensitivity was tested instead and yielded similar results for the image-based material decomposition task, as long as the fact that one incident photon can increase multiple counters across neighboring detector pixels is taken into account. CONCLUSIONS: The IMA is computationally efficient as it required about 10(2) random numbers per ray incident on a detector pixel instead of an estimated 10(8) random numbers per ray as Monte Carlo approaches would need. The spatial-spectral correlations as described by IMA are not important for the studied image-based material decomposition task. Respecting the absolute photon counts and thus the multiple counter increases by a single x-ray photon, the same material decomposition performance could be obtained with a simpler detector description using the energy bin sensitivity. PMID- 27370114 TI - Consequences of air around an ionization chamber: Are existing solid phantoms suitable for reference dosimetry on an MR-linac? AB - PURPOSE: A protocol for reference dosimetry for the MR-linac is under development. The 1.5 T magnetic field changes the mean path length of electrons in an air-filled ionization chamber but has little effect on the electron trajectories in a surrounding phantom. It is therefore necessary to correct the response of an ionization chamber for the influence of the magnetic field. Solid phantoms are used for dosimetry measurements on the MR-linac, but air is present between the chamber wall and phantom insert. This study aimed to determine if this air influences the ion chamber measurements on the MR-linac. The absolute response of the chamber and reproducibility of dosimetry measurements were assessed on an MR-linac in solid and water phantoms. The sensitivity of the chamber response to the distribution of air around the chamber was also investigated. METHODS: Measurements were performed on an MR-linac and replicated on a conventional linac for five chambers. The response of three waterproof chambers was measured with air and with water between the chamber and the insert to measure the influence of the air volume on absolute chamber response. The distribution of air around the chamber was varied indirectly by rotating each chamber about the longitudinal chamber axis in a solid phantom and a water phantom (waterproof chambers only) and measuring the angular dependence of the chamber response, and varied directly by displacing the chamber in the phantom insert using a paper shim positioned at different orientations between the chamber casing and the insert. RESULTS: The responses of the three waterproof chambers measured on the MR-linac were 0.7%-1.2% higher with water than air in the chamber insert. The responses of the chambers on the conventional linac changed by less than 0.3% when air in the insert was replaced with water. The angular dependence of the chambers ranged from 0.6% to 1.9% in the solid phantom on the MR-linac but was less than 0.5% in water on the MR-linac and less than 0.3% in the solid phantom on the conventional linac. Inserting a shim around the chamber induced changes of the chamber response in a magnetic field of up to 2.2%, but the change in chamber response on the conventional linac was less than 0.3%. CONCLUSIONS: The interaction between the magnetic field and secondary electrons in the air around the chamber reduces the charge collected from 0.7% to 1.2%. The large angular dependence of ion chambers measured in the plastic phantom in a magnetic field appears to arise from a change of air distribution as the chamber is moved within the insert, rather than an intrinsic isotropy of the chamber sensitivity to radiation. It is recommended that reference dosimetry measurements on the MR-linac can be performed only in water, rather than in existing plastic phantoms. PMID- 27370115 TI - Online 3D EPID-based dose verification: Proof of concept. AB - PURPOSE: Delivery errors during radiotherapy may lead to medical harm and reduced life expectancy for patients. Such serious incidents can be avoided by performing dose verification online, i.e., while the patient is being irradiated, creating the possibility of halting the linac in case of a large overdosage or underdosage. The offline EPID-based 3D in vivo dosimetry system clinically employed at our institute is in principle suited for online treatment verification, provided the system is able to complete 3D dose reconstruction and verification within 420 ms, the present acquisition time of a single EPID frame. It is the aim of this study to show that our EPID-based dosimetry system can be made fast enough to achieve online 3D in vivo dose verification. METHODS: The current dose verification system was sped up in two ways. First, a new software package was developed to perform all computations that are not dependent on portal image acquisition separately, thus removing the need for doing these calculations in real time. Second, the 3D dose reconstruction algorithm was sped up via a new, multithreaded implementation. Dose verification was implemented by comparing planned with reconstructed 3D dose distributions delivered to two regions in a patient: the target volume and the nontarget volume receiving at least 10 cGy. In both volumes, the mean dose is compared, while in the nontarget volume, the near-maximum dose (D2) is compared as well. The real-time dosimetry system was tested by irradiating an anthropomorphic phantom with three VMAT plans: a 6 MV head-and-neck treatment plan, a 10 MV rectum treatment plan, and a 10 MV prostate treatment plan. In all plans, two types of serious delivery errors were introduced. The functionality of automatically halting the linac was also implemented and tested. RESULTS: The precomputation time per treatment was ~180 s/treatment arc, depending on gantry angle resolution. The complete processing of a single portal frame, including dose verification, took 266 +/- 11 ms on a dual octocore Intel Xeon E5-2630 CPU running at 2.40 GHz. The introduced delivery errors were detected after 5-10 s irradiation time. CONCLUSIONS: A prototype online 3D dose verification tool using portal imaging has been developed and successfully tested for two different kinds of gross delivery errors. Thus, online 3D dose verification has been technologically achieved. PMID- 27370116 TI - Quantitative analysis of treatment process time and throughput capacity for spot scanning proton therapy. AB - PURPOSE: To determine the patient throughput and the overall efficiency of the spot scanning system by analyzing treatment time, equipment availability, and maximum daily capacity for the current spot scanning port at Proton Therapy Center Houston and to assess the daily throughput capacity for a hypothetical spot scanning proton therapy center. METHODS: At their proton therapy center, the authors have been recording in an electronic medical record system all treatment data, including disease site, number of fields, number of fractions, delivered dose, energy, range, number of spots, and number of layers for every treatment field. The authors analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the patient census, patient distribution as a function of the number of fields and total target volume, and equipment clinical availability. The duration of each treatment session from patient walk-in to patient walk-out of the spot scanning treatment room was measured for 64 patients with head and neck, central nervous system, thoracic, and genitourinary cancers. The authors retrieved data for total target volume and the numbers of layers and spots for all fields from treatment plans for a total of 271 patients (including the above 64 patients). A sensitivity analysis of daily throughput capacity was performed by varying seven parameters in a throughput capacity model. RESULTS: The mean monthly equipment clinical availability for the spot scanning port in April 2012-March 2015 was 98.5%. Approximately 1500 patients had received spot scanning proton therapy as of March 2015. The major disease sites treated in September 2012-August 2014 were the genitourinary system (34%), head and neck (30%), central nervous system (21%), and thorax (14%), with other sites accounting for the remaining 1%. Spot scanning beam delivery time increased with total target volume and accounted for approximately 30%-40% of total treatment time for the total target volumes exceeding 200 cm(3), which was the case for more than 80% of the patients in this study. When total treatment time was modeled as a function of the number of fields and total target volume, the model overestimated total treatment time by 12% on average, with a standard deviation of 32%. A sensitivity analysis of throughput capacity for a hypothetical four-room spot scanning proton therapy center identified several priority items for improvements in throughput capacity, including operation time, beam delivery time, and patient immobilization and setup time. CONCLUSIONS: The spot scanning port at our proton therapy center has operated at a high performance level and has been used to treat a large number of complex cases. Further improvements in efficiency may be feasible in the areas of facility operation, beam delivery, patient immobilization and setup, and optimization of treatment scheduling. PMID- 27370117 TI - Two schemes for quantitative photoacoustic tomography based on Monte Carlo simulation. AB - PURPOSE: The aim of this study was to develop novel methods for photoacoustically determining the optical absorption coefficient of biological tissues using Monte Carlo (MC) simulation. METHODS: In this study, the authors propose two quantitative photoacoustic tomography (PAT) methods for mapping the optical absorption coefficient. The reconstruction methods combine conventional PAT with MC simulation in a novel way to determine the optical absorption coefficient of biological tissues or organs. Specifically, the authors' two schemes were theoretically and experimentally examined using simulations, tissue-mimicking phantoms, ex vivo, and in vivo tests. In particular, the authors explored these methods using several objects with different absorption contrasts embedded in turbid media and by using high-absorption media when the diffusion approximation was not effective at describing the photon transport. RESULTS: The simulations and experimental tests showed that the reconstructions were quantitatively accurate in terms of the locations, sizes, and optical properties of the targets. The positions of the recovered targets were accessed by the property profiles, where the authors discovered that the off center error was less than 0.1 mm for the circular target. Meanwhile, the sizes and quantitative optical properties of the targets were quantified by estimating the full width half maximum of the optical absorption property. Interestingly, for the reconstructed sizes, the authors discovered that the errors ranged from 0 for relatively small-size targets to 26% for relatively large-size targets whereas for the recovered optical properties, the errors ranged from 0% to 12.5% for different cases. CONCLUSIONS: The authors found that their methods can quantitatively reconstruct absorbing objects of different sizes and optical contrasts even when the diffusion approximation is unable to accurately describe the photon propagation in biological tissues. In particular, their methods are able to resolve the intrinsic difficulties that occur when quantitative PAT is conducted by combining conventional PAT with the diffusion approximation or with radiation transport modeling. PMID- 27370118 TI - Single-energy computed tomography-based pulmonary perfusion imaging: Proof-of principle in a canine model. AB - PURPOSE: Radiotherapy (RT) that selectively avoids irradiating highly functional lung regions may reduce pulmonary toxicity, which is substantial in lung cancer RT. Single-energy computed tomography (CT) pulmonary perfusion imaging has several advantages (e.g., higher resolution) over other modalities and has great potential for widespread clinical implementation, particularly in RT. The purpose of this study was to establish proof-of-principle for single-energy CT perfusion imaging. METHODS: Single-energy CT perfusion imaging is based on the following: (1) acquisition of end-inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast agents, (2) deformable image registration (DIR) for spatial mapping of those two CT image data sets, and (3) subtraction of the precontrast image data set from the postcontrast image data set, yielding a map of regional Hounsfield unit (HU) enhancement, a surrogate for regional perfusion. In a protocol approved by the institutional animal care and use committee, the authors acquired CT scans in the prone position for a total of 14 anesthetized canines (seven canines with normal lungs and seven canines with diseased lungs). The elastix algorithm was used for DIR. The accuracy of DIR was evaluated based on the target registration error (TRE) of 50 anatomic pulmonary landmarks per subject for 10 randomly selected subjects as well as on singularities (i.e., regions where the displacement vector field is not bijective). Prior to perfusion computation, HUs of the precontrast end inspiratory image were corrected for variation in the lung inflation level between the precontrast and postcontrast end-inspiratory CT scans, using a model built from two additional precontrast CT scans at end-expiration and midinspiration. The authors also assessed spatial heterogeneity and gravitationally directed gradients of regional perfusion for normal lung subjects and diseased lung subjects using a two-sample two-tailed t-test. RESULTS: The mean TRE (and standard deviation) was 0.6 +/- 0.7 mm (smaller than the voxel dimension) for DIR between pre contrast and postcontrast end-inspiratory CT image data sets. No singularities were observed in the displacement vector fields. The mean HU enhancement (and standard deviation) was 37.3 +/- 10.5 HU for normal lung subjects and 30.7 +/- 13.5 HU for diseased lung subjects. Spatial heterogeneity of regional perfusion was found to be higher for diseased lung subjects than for normal lung subjects, i.e., a mean coefficient of variation of 2.06 vs 1.59 (p = 0.07). The average gravitationally directed gradient was strong and significant (R(2) = 0.99, p < 0.01) for normal lung dogs, whereas it was moderate and nonsignificant (R(2) = 0.61, p = 0.12) for diseased lung dogs. CONCLUSIONS: This canine study demonstrated the accuracy of DIR with subvoxel TREs on average, higher spatial heterogeneity of regional perfusion for diseased lung subjects than for normal lung subjects, and a strong gravitationally directed gradient for normal lung subjects, providing proof-of-principle for single-energy CT pulmonary perfusion imaging. Further studies such as comparison with other perfusion imaging modalities will be necessary to validate the physiological significance. PMID- 27370119 TI - Aging effect on microcirculation: A multiscale entropy approach on laser speckle contrast images. AB - PURPOSE: It has long been known that age plays a crucial role in the deterioration of microvessels. The assessment of such deteriorations can be achieved by monitoring microvascular blood flow. Laser speckle contrast imaging (LSCI) is a powerful optical imaging tool that provides two-dimensional information on microvascular blood flow. The technique has recently been commercialized, and hence, few works discuss the postacquisition processing of laser speckle contrast images recorded in vivo. By applying entropy-based complexity measures to LSCI time series, we present herein the first attempt to study the effect of aging on microcirculation by measuring the complexity of microvascular signals over multiple time scales. METHODS: Forearm skin microvascular blood flow was studied with LSCI in 18 healthy subjects. The subjects were subdivided into two age groups: younger (20-30 years old, n = 9) and older (50-68 years old, n = 9). To estimate age-dependent changes in microvascular blood flow, we applied three entropy-based complexity algorithms to LSCI time series. RESULTS: The application of entropy-based complexity algorithms to LSCI time series can differentiate younger from older groups: the data fluctuations in the younger group have a significantly higher complexity than those obtained from the older group. CONCLUSIONS: The effect of aging on microcirculation can be estimated by using entropy-based complexity algorithms to LSCI time series. PMID- 27370120 TI - Technical Note: Gray tracking in medical color displays-A report of Task Group 196. AB - PURPOSE: The authors discuss measurement methods and instrumentation useful for the characterization of the gray tracking performance of medical color monitors for diagnostic applications. The authors define gray tracking as the variability in the chromaticity of the gray levels in a color monitor. METHODS: The authors present data regarding the capability of color measurement instruments with respect to their abilities to measure a target white point corresponding to the CIE Standard Illuminant D65 at different luminance values within the grayscale palette of a medical display. The authors then discuss evidence of significant differences in performance among color measurement instruments currently available for medical physicists to perform calibrations and image quality checks for the consistent representation of color in medical displays. In addition, the authors introduce two metrics for quantifying grayscale chromaticity consistency of gray tracking. RESULTS: The authors' findings show that there is an order of magnitude difference in the accuracy of field and reference instruments. The gray tracking metrics quantify how close the grayscale chromaticity is to the chromaticity of the full white point (equal amounts of red, green, and blue at maximum level) or to consecutive levels (equal values for red, green, and blue), with a lower value representing an improved grayscale tracking performance. An illustrative example of how to calculate and report the gray tracking performance according to the Task Group definitions is provided. CONCLUSIONS: The authors' proposed methodology for characterizing the grayscale degradation in chromaticity for color monitors that can be used to establish standards and procedures aiding in the quality control testing of color displays and color measurement instrumentation. PMID- 27370121 TI - Clinical evaluation of a medical high dynamic range display. AB - PURPOSE: Recent new medical displays do have higher contrast and higher luminance but do not have a High Dynamic Range (HDR). HDR implies a minimum luminance value close to zero. A medical HDR display prototype based on two Liquid Crystal layers has been developed. The goal of this study is to evaluate the potential clinical benefit of such display in comparison with a low dynamic range (LDR) display. METHODS: The study evaluated the clinical performance of the displays in a search and detection task. Eight radiologists read chest x-ray images some of which contained simulated lung nodules. The study used a JAFROC (Jacknife Free Receiver Operating Characteristic) approach for analyzing FROC data. The calculated figure of merit (FoM) is the probability that a lesion is rated higher than all rated nonlesions on all images. Time per case and accuracy for locating the center of the nodules were also compared. The nodules were simulated using Samei's model. 214 CR and DR images [half were "healthy images" (chest nodule-free) and half "diseased images"] were used resulting in a total number of nodules equal to 199 with 25 images with 1 nodule, 51 images with 2 nodules, and 24 images with 3 nodules. A dedicated software interface was designed for visualizing the images for each session. For the JAFROC1 statistical analysis, the study is done per nodule category: all nodules, difficult nodules, and very difficult nodules. RESULTS: For all nodules, the averaged FoMHDR is slightly higher than FoMLDR with 0.09% of difference. For the difficult nodules, the averaged FoMHDR is slightly higher than FoMLDR with 1.38% of difference. The averaged FoMHDR is slightly higher than FoMLDR with 0.71% of difference. For the true positive fraction (TPF), both displays (the HDR and the LDR ones) have similar TPF for all nodules, but looking at difficult and very difficult nodules, there are more TP for the HDR display. The true positive fraction has been also computed in function of the local average luminance around the nodules. For the lowest luminance range, there is more than 30% in favor of the HDR display. For the highest luminance range, there is less than 6% in favor of the LDR display. CONCLUSIONS: This study shows the potential benefit of using a HDR display in radiology. PMID- 27370122 TI - Characterization of air temperature in modern ion chambers due to phantom geometry and ambient temperature changes. AB - PURPOSE: Temperature and pressure corrections are necessary to account for the varying mass of air in the sensitive volume of a vented ionization chamber (IC) when performing absolute dose measurements. Locations commonly used to measure the presumed IC air temperature may not accurately represent the chamber cavity air temperature, and phantoms undergoing temperature changes further compound the problem. Prior studies have characterized thermal equilibrium in separate phantoms for Farmer chambers alone. However, the purpose of this study was to characterize the cavity air temperature dependence on changes in the ambient temperature and phantom geometry configuration for a wider and more modern variety of chambers to determine if previously published wait times apply to these chambers as well. METHODS: Thermal conduction properties were experimentally investigated by modifying a PTW 0.3 cm(3) Semiflex IC with a thermocouple replacing the central electrode. Air cavity temperature versus time was recorded in three phantom geometries characteristic of common absolute dose measurements. The phantoms were (15 +/- 1) degrees C before measurement with an IC at the treatment vault temperature of (21 +/- 1) degrees C. Simulations were conducted to provide a theoretical basis for the measurements and to simulate temperature response of a PTW PinPoint(r) and Farmer chamber. The simulation methods were first validated by comparison with measured Semiflex chamber thermal response curves before extension to the other chambers. RESULTS: Two thermal equilibria curves were recorded on different time scales. IC temperature initially dropped to the colder phantom temperature but subsequently increased as the phantom itself equilibrated with the warmer room temperature. In a large phantom of dimensions (25.5 * 25.5 * 23.4) cm(3), 3 min was required before the IC temperature reached within 0.5 degrees C of its equilibrium within the phantom. Similarly, wait times of 2 min were needed for 7.5 and 2 cm slab phantoms. CONCLUSIONS: Recording of temperature in the phantom was deemed far more accurate than measurement in ambient air due to the air cavity thermally equilibrating with phantom temperature instead of the vented ambient air. Wait times of 3 and 2 min are needed for a cube and 7.5 cm slab phantom, respectively, to achieve 0.2% dosimetric accuracy (temperature accuracy of 0.5 degrees C). Chamber volume alone did not determine wait times, as a 0.3 cm(3) IC required a longer wait time than a Farmer chamber, suggesting wall thickness as an important variable as well. PMID- 27370123 TI - A GPU-accelerated Monte Carlo dose calculation platform and its application toward validating an MRI-guided radiation therapy beam model. AB - PURPOSE: The clinical commissioning of IMRT subject to a magnetic field is challenging. The purpose of this work is to develop a GPU-accelerated Monte Carlo dose calculation platform based on penelope and then use the platform to validate a vendor-provided MRIdian head model toward quality assurance of clinical IMRT treatment plans subject to a 0.35 T magnetic field. METHODS: penelope was first translated from fortran to c++ and the result was confirmed to produce equivalent results to the original code. The c++ code was then adapted to cuda in a workflow optimized for GPU architecture. The original code was expanded to include voxelized transport with Woodcock tracking, faster electron/positron propagation in a magnetic field, and several features that make gpenelope highly user friendly. Moreover, the vendor-provided MRIdian head model was incorporated into the code in an effort to apply gpenelope as both an accurate and rapid dose validation system. A set of experimental measurements were performed on the MRIdian system to examine the accuracy of both the head model and gpenelope. Ultimately, gpenelope was applied toward independent validation of patient doses calculated by MRIdian's kmc. RESULTS: An acceleration factor of 152 was achieved in comparison to the original single-thread fortran implementation with the original accuracy being preserved. For 16 treatment plans including stomach (4), lung (2), liver (3), adrenal gland (2), pancreas (2), spleen(1), mediastinum (1), and breast (1), the MRIdian dose calculation engine agrees with gpenelope with a mean gamma passing rate of 99.1% +/- 0.6% (2%/2 mm). CONCLUSIONS: A Monte Carlo simulation platform was developed based on a GPU- accelerated version of penelope. This platform was used to validate that both the vendor-provided head model and fast Monte Carlo engine used by the MRIdian system are accurate in modeling radiation transport in a patient using 2%/2 mm gamma criteria. Future applications of this platform will include dose validation and accumulation, IMRT optimization, and dosimetry system modeling for next generation MR-IGRT systems. PMID- 27370124 TI - Impact of SPECT corrections on 3D-dosimetry for liver transarterial radioembolization using the patient relative calibration methodology. AB - PURPOSE: Many centers aim to plan liver transarterial radioembolization (TARE) with dosimetry, even without CT-based attenuation correction (AC), or with unoptimized scatter correction (SC) methods. This work investigates the impact of presence vs absence of such corrections, and limited spatial resolution, on 3D dosimetry for TARE. METHODS: Three voxelized phantoms were derived from CT images of real patients with different body sizes. Simulations of (99m)Tc-SPECT projections were performed with the SIMIND code, assuming three activity distributions in the liver: uniform, inside a "liver's segment," or distributing multiple uptaking nodules ("nonuniform liver"), with a tumoral liver/healthy parenchyma ratio of 5:1. Projection data were reconstructed by a commercial workstation, with OSEM protocol not specifically optimized for dosimetry (spatial resolution of 12.6 mm), with/without SC (optimized, or with parameters predefined by the manufacturer; dual energy window), and with/without AC. Activity in voxels was calculated by a relative calibration, assuming identical microspheres and (99m)Tc-SPECT counts spatial distribution. 3D dose distributions were calculated by convolution with (90)Y voxel S-values, assuming permanent trapping of microspheres. Cumulative dose-volume histograms in lesions and healthy parenchyma from different reconstructions were compared with those obtained from the reference biodistribution (the "gold standard," GS), assessing differences for D95%, D70%, and D50% (i.e., minimum value of the absorbed dose to a percentage of the irradiated volume). gamma tool analysis with tolerance of 3%/13 mm was used to evaluate the agreement between GS and simulated cases. The influence of deep breathing was studied, blurring the reference biodistributions with a 3D anisotropic gaussian kernel, and performing the simulations once again. RESULTS: Differences of the dosimetric indicators were noticeable in some cases, always negative for lesions and distributed around zero for parenchyma. Application of AC and SC reduced systematically the differences for lesions by 5%-14% for a liver segment, and by 7%-12% for a nonuniform liver. For parenchyma, the data trend was less clear, but the overall range of variability passed from -10%/40% for a liver segment, and -10%/20% for a nonuniform liver, to -13%/6% in both cases. Applying AC, SC with preset parameters gave similar results to optimized SC, as confirmed by gamma tool analysis. Moreover, gamma analysis confirmed that solely AC and SC are not sufficient to obtain accurate 3D dose distribution. With breathing, the accuracy worsened severely for all dosimetric indicators, above all for lesions: with AC and optimized SC, -38%/-13% in liver's segment, -61%/ 40% in the nonuniform liver. For parenchyma, D50% resulted always less sensitive to breathing and sub-optimal correction methods (difference overall range: 7%/13%). CONCLUSIONS: Reconstruction protocol optimization, AC, SC, PVE and respiratory motion corrections should be implemented to obtain the best possible dosimetric accuracy. On the other side, thanks to the relative calibration, D50% inaccuracy for the healthy parenchyma from absence of AC was less than expected, while the optimization of SC was scarcely influent. The relative calibration therefore allows to perform TARE planning, basing on D50% for the healthy parenchyma, even without AC or with suboptimal corrections, rather than rely on nondosimetric methods. PMID- 27370125 TI - Coded excitation ultrasonic needle tracking: An in vivo study. AB - PURPOSE: Accurate and efficient guidance of medical devices to procedural targets lies at the heart of interventional procedures. Ultrasound imaging is commonly used for device guidance, but determining the location of the device tip can be challenging. Various methods have been proposed to track medical devices during ultrasound-guided procedures, but widespread clinical adoption has remained elusive. With ultrasonic tracking, the location of a medical device is determined by ultrasonic communication between the ultrasound imaging probe and a transducer integrated into the medical device. The signal-to-noise ratio (SNR) of the transducer data is an important determinant of the depth in tissue at which tracking can be performed. In this paper, the authors present a new generation of ultrasonic tracking in which coded excitation is used to improve the SNR without spatial averaging. METHODS: A fiber optic hydrophone was integrated into the cannula of a 20 gauge insertion needle. This transducer received transmissions from the ultrasound imaging probe, and the data were processed to obtain a tracking image of the needle tip. Excitation using Barker or Golay codes was performed to improve the SNR, and conventional bipolar excitation was performed for comparison. The performance of the coded excitation ultrasonic tracking system was evaluated in an in vivo ovine model with insertions to the brachial plexus and the uterine cavity. RESULTS: Coded excitation significantly increased the SNRs of the tracking images, as compared with bipolar excitation. During an insertion to the brachial plexus, the SNR was increased by factors of 3.5 for Barker coding and 7.1 for Golay coding. During insertions into the uterine cavity, these factors ranged from 2.9 to 4.2 for Barker coding and 5.4 to 8.5 for Golay coding. The maximum SNR was 670, which was obtained with Golay coding during needle withdrawal from the brachial plexus. Range sidelobe artifacts were observed in tracking images obtained with Barker coded excitation, and they were visually absent with Golay coded excitation. The spatial tracking accuracy was unaffected by coded excitation. CONCLUSIONS: Coded excitation is a viable method for improving the SNR in ultrasonic tracking without compromising spatial accuracy. This method provided SNR increases that are consistent with theoretical expectations, even in the presence of physiological motion. With the ultrasonic tracking system in this study, the SNR increases will have direct clinical implications in a broad range of interventional procedures by improving visibility of medical devices at large depths. PMID- 27370126 TI - Segmentation of malignant lesions in 3D breast ultrasound using a depth-dependent model. AB - PURPOSE: Automated 3D breast ultrasound (ABUS) has been proposed as a complementary screening modality to mammography for early detection of breast cancers. To facilitate the interpretation of ABUS images, automated diagnosis and detection techniques are being developed, in which malignant lesion segmentation plays an important role. However, automated segmentation of cancer in ABUS is challenging since lesion edges might not be well defined. In this study, the authors aim at developing an automated segmentation method for malignant lesions in ABUS that is robust to ill-defined cancer edges and posterior shadowing. METHODS: A segmentation method using depth-guided dynamic programming based on spiral scanning is proposed. The method automatically adjusts aggressiveness of the segmentation according to the position of the voxels relative to the lesion center. Segmentation is more aggressive in the upper part of the lesion (close to the transducer) than at the bottom (far away from the transducer), where posterior shadowing is usually visible. The authors used Dice similarity coefficient (Dice) for evaluation. The proposed method is compared to existing state of the art approaches such as graph cut, level set, and smart opening and an existing dynamic programming method without depth dependence. RESULTS: In a dataset of 78 cancers, our proposed segmentation method achieved a mean Dice of 0.73 +/- 0.14. The method outperforms an existing dynamic programming method (0.70 +/- 0.16) on this task (p = 0.03) and it is also significantly (p < 0.001) better than graph cut (0.66 +/- 0.18), level set based approach (0.63 +/- 0.20) and smart opening (0.65 +/- 0.12). CONCLUSIONS: The proposed depth-guided dynamic programming method achieves accurate breast malignant lesion segmentation results in automated breast ultrasound. PMID- 27370127 TI - Accuracy of a dose-area product compared to an absorbed dose to water at a point in a 2 cm diameter field. AB - PURPOSE: Graphite calorimeters with a core diameter larger than the beam can be used to establish dosimetric references in small fields. The dose-area product (DAP) measured can theoretically be linked to an absorbed dose at a point by the determination of a profile correction. This study aims at comparing the DAP-based protocol to the usual absorbed dose at a point protocol in a 2 cm diameter field for which both references exist. METHODS: Two calorimeters were used, respectively, with a sensitive volume of 0.6 cm (for the absorbed dose at a point measurement) and 3 cm diameter (for the DAP measurement). Profile correction was calculated from a 2D dose mapping using three detectors: a PinPoint chamber, a synthetic diamond, and EBT3 films. A specific protocol to read EBT3 films was implemented and the dose-rate and energy dependences were studied to assure a precise measurement, especially in the penumbra and out-of-field regions. RESULTS: EBT3 films were found independent on dose rates over the range studied but showed a strong under-response (18%) at low energies. Depending on the dosimeter used for calculating the profile correction, a deviation of 0.8% (PinPoint chamber), 0.9% (diamond), or 1.9% (EBT3 films) was observed between the calibration coefficient derived from DAP measurements and the one directly established in terms of absorbed dose to water at a point. CONCLUSIONS: The DAP method can currently be linked to the classical dosimetric reference system based in an absorbed dose at a point only with a confidence interval of 95% (k = 2). None of the detectors studied can be used to determine an absorbed dose to water at a point from a DAP measurement with an uncertainty smaller than 1.2%. PMID- 27370128 TI - Technical Note: Improving the VMERGE treatment planning algorithm for rotational radiotherapy. AB - PURPOSE: The authors revisit the VMERGE treatment planning algorithm by Craft et al. ["Multicriteria VMAT optimization," Med. Phys. 39, 686-696 (2012)] for arc therapy planning and propose two changes to the method that are aimed at improving the achieved trade-off between treatment time and plan quality at little additional planning time cost, while retaining other desirable properties of the original algorithm. METHODS: The original VMERGE algorithm first computes an "ideal," high quality but also highly time consuming treatment plan that irradiates the patient from all possible angles in a fine angular grid with a highly modulated beam and then makes this plan deliverable within practical treatment time by an iterative fluence map merging and sequencing algorithm. We propose two changes to this method. First, we regularize the ideal plan obtained in the first step by adding an explicit constraint on treatment time. Second, we propose a different merging criterion that comprises of identifying and merging adjacent maps whose merging results in the least degradation of radiation dose. RESULTS: The effect of both suggested modifications is evaluated individually and jointly on clinical prostate and paraspinal cases. Details of the two cases are reported. CONCLUSIONS: In the authors' computational study they found that both proposed modifications, especially the regularization, yield noticeably improved treatment plans for the same treatment times than what can be obtained using the original VMERGE method. The resulting plans match the quality of 20-beam step-and shoot IMRT plans with a delivery time of approximately 2 min. PMID- 27370129 TI - Technical Note: Image filtering to make computer-aided detection robust to image reconstruction kernel choice in lung cancer CT screening. AB - PURPOSE: In lung cancer computed tomography (CT) screening, the performance of a computer-aided detection (CAD) system depends on the selection of the image reconstruction kernel. To reduce this dependence on reconstruction kernels, the authors propose a novel application of an image filtering method previously proposed by their group. METHODS: The proposed filtering process uses the ratio of modulation transfer functions (MTFs) of two reconstruction kernels as a filtering function in the spatial-frequency domain. This method is referred to as MTFratio filtering. Test image data were obtained from CT screening scans of 67 subjects who each had one nodule. Images were reconstructed using two kernels: fSTD (for standard lung imaging) and fSHARP (for sharp edge-enhancement lung imaging). The MTFratio filtering was implemented using the MTFs measured for those kernels and was applied to the reconstructed fSHARP images to obtain images that were similar to the fSTD images. A mean filter and a median filter were applied (separately) for comparison. All reconstructed and filtered images were processed using their prototype CAD system. RESULTS: The MTFratio filtered images showed excellent agreement with the fSTD images. The standard deviation for the difference between these images was very small, ~6.0 Hounsfield units (HU). However, the mean and median filtered images showed larger differences of ~48.1 and ~57.9 HU from the fSTD images, respectively. The free-response receiver operating characteristic (FROC) curve for the fSHARP images indicated poorer performance compared with the FROC curve for the fSTD images. The FROC curve for the MTFratio filtered images was equivalent to the curve for the fSTD images. However, this similarity was not achieved by using the mean filter or median filter. CONCLUSIONS: The accuracy of MTFratio image filtering was verified and the method was demonstrated to be effective for reducing the kernel dependence of CAD performance. PMID- 27370130 TI - Technical Note: An investigation of polarity effects for wide-angle free-air chambers. AB - PURPOSE: Wide-angle free-air chambers (WAFACs) are used as primary standard measurement devices for establishing the air-kerma strength of low-energy, low dose rate brachytherapy seeds. The National Research Council of Canada (NRC) is commissioning a primary standard wide-angle free-air chamber (NRC WAFAC) to serve the calibration needs of Canadian clients. The University of Wisconsin has developed a similar variable-aperture free-air chamber (UW VAFAC) to be used as a research tool. As part of the NRC commissioning, measurements were carried out for both polarities of the applied bias voltage and the resulting effects were observed to be very large. Similar effects were identified with the UW VAFAC. The authors describe the measurements carried out to determine the underlying causes of the polarity effect and the approach used to eliminate it. METHODS: The NRC WAFAC is based on the WAFAC design developed at the National Institute of Standards and Technology in the USA. Charge measurements for (125)I and (241)Am sources were carried out for both negative and positive polarities on the NRC WAFAC and UW VAFAC. Two aperture sizes were also investigated with the UW VAFAC. In addition, measurements on the NRC WAFAC were carried out with a small bias between the collecting electrode and the shield foil at the downstream end of the chamber. To mitigate all of the polarity effects, the downstream surface of the collecting electrode was covered with a thin layer of graphite on both the NRC and UW chambers. RESULTS: Both chamber designs showed a difference of more than 30 % between the charge collected with positive and negative bias voltages for the smallest electrode separation. It was shown for the NRC WAFAC that charge could be collected in the small gap downstream of the collecting volume by applying a voltage between the shield foil and the collecting electrode, even though an insulating foil (Mylar or polyimide film) separated the conducting surface from the small gap region. The unwanted additional current was shown to be proportional to the size of the aperture for the UW VAFAC. The extra ionization produced in the small gap region was eliminated for both chambers by covering the insulating side of the collecting electrode with a grounded conducting layer. CONCLUSIONS: The small gap region downstream of the collecting electrode in the NRC WAFAC and UW VAFAC can serve as an unwanted source of ion current. It is concluded that a residual electric field in the small gap region may lead to ion transport and to charge being trapped on the surface of the foil. The foil then acts as a capacitor with an equal charge, but of opposite sign, being attracted to the conducting surface. Covering the back of the collecting electrode surface with a grounded conducting layer eliminated the polarity effect. PMID- 27370131 TI - Correlation of FMISO simulations with pimonidazole-stained tumor xenografts: A question of O2 consumption? AB - PURPOSE: To compare a dedicated simulation model for hypoxia PET against tumor microsections stained for different parameters of the tumor microenvironment. The model can readily be adapted to a variety of conditions, such as different human head and neck squamous cell carcinoma (HNSCC) xenograft tumors. METHODS: Nine different HNSCC tumor models were transplanted subcutaneously into nude mice. Tumors were excised and immunoflourescently labeled with pimonidazole, Hoechst 33342, and CD31, providing information on hypoxia, perfusion, and vessel distribution, respectively. Hoechst and CD31 images were used to generate maps of perfused blood vessels on which tissue oxygenation and the accumulation of the hypoxia tracer FMISO were mathematically simulated. The model includes a Michaelis-Menten relation to describe the oxygen consumption inside tissue. The maximum oxygen consumption rate M0 was chosen as the parameter for a tumor specific optimization as it strongly influences tracer distribution. M0 was optimized on each tumor slice to reach optimum correlations between FMISO concentration 4 h postinjection and pimonidazole staining intensity. RESULTS: After optimization, high pixel-based correlations up to R(2) = 0.85 were found for individual tissue sections. Experimental pimonidazole images and FMISO simulations showed good visual agreement, confirming the validity of the approach. Median correlations per tumor model varied significantly (p < 0.05), with R(2) ranging from 0.20 to 0.54. The optimum maximum oxygen consumption rate M0 differed significantly (p < 0.05) between tumor models, ranging from 2.4 to 5.2 mm Hg/s. CONCLUSIONS: It is feasible to simulate FMISO distributions that match the pimonidazole retention patterns observed in vivo. Good agreement was obtained for multiple tumor models by optimizing the oxygen consumption rate, M0, whose optimum value differed significantly between tumor models. PMID- 27370132 TI - Experimental and Monte Carlo studies of fluence corrections for graphite calorimetry in low- and high-energy clinical proton beams. AB - PURPOSE: The aim of this study was to determine fluence corrections necessary to convert absorbed dose to graphite, measured by graphite calorimetry, to absorbed dose to water. Fluence corrections were obtained from experiments and Monte Carlo simulations in low- and high-energy proton beams. METHODS: Fluence corrections were calculated to account for the difference in fluence between water and graphite at equivalent depths. Measurements were performed with narrow proton beams. Plane-parallel-plate ionization chambers with a large collecting area compared to the beam diameter were used to intercept the whole beam. High- and low-energy proton beams were provided by a scanning and double scattering delivery system, respectively. A mathematical formalism was established to relate fluence corrections derived from Monte Carlo simulations, using the fluka code [A. Ferrari et al., "fluka: A multi-particle transport code," in CERN 2005-10, INFN/TC 05/11, SLAC-R-773 (2005) and T. T. Bohlen et al., "The fluka Code: Developments and challenges for high energy and medical applications," Nucl. Data Sheets 120, 211-214 (2014)], to partial fluence corrections measured experimentally. RESULTS: A good agreement was found between the partial fluence corrections derived by Monte Carlo simulations and those determined experimentally. For a high-energy beam of 180 MeV, the fluence corrections from Monte Carlo simulations were found to increase from 0.99 to 1.04 with depth. In the case of a low-energy beam of 60 MeV, the magnitude of fluence corrections was approximately 0.99 at all depths when calculated in the sensitive area of the chamber used in the experiments. Fluence correction calculations were also performed for a larger area and found to increase from 0.99 at the surface to 1.01 at greater depths. CONCLUSIONS: Fluence corrections obtained experimentally are partial fluence corrections because they account for differences in the primary and part of the secondary particle fluence. A correction factor, F(d), has been established to relate fluence corrections defined theoretically to partial fluence corrections derived experimentally. The findings presented here are also relevant to water and tissue-equivalent-plastic materials given their carbon content. PMID- 27370133 TI - Sensitivity of the diagnostic radiological index of protection to procedural factors in fluoroscopy. AB - PURPOSE: To evaluate the sensitivity of the diagnostic radiological index of protection (DRIP), used to quantify the protective value of radioprotective garments, to procedural factors in fluoroscopy in an effort to determine an appropriate set of scatter-mimicking primary beams to be used in measuring the DRIP. METHODS: Monte Carlo simulations were performed to determine the shape of the scattered x-ray spectra incident on the operator in different clinical fluoroscopy scenarios, including interventional radiology and interventional cardiology (IC). Two clinical simulations studied the sensitivity of the scattered spectrum to gantry angle and patient size, while technical factors were varied according to measured automatic dose rate control (ADRC) data. Factorial simulations studied the sensitivity of the scattered spectrum to gantry angle, field of view, patient size, and beam quality for constant technical factors. Average energy (Eavg) was the figure of merit used to condense fluence in each energy bin to a single numerical index. RESULTS: Beam quality had the strongest influence on the scattered spectrum in fluoroscopy. Many procedural factors affect the scattered spectrum indirectly through their effect on primary beam quality through ADRC, e.g., gantry angle and patient size. Lateral C-arm rotation, common in IC, increased the energy of the scattered spectrum, regardless of the direction of rotation. The effect of patient size on scattered radiation depended on ADRC characteristics, patient size, and procedure type. CONCLUSIONS: The scattered spectrum striking the operator in fluoroscopy is most strongly influenced by primary beam quality, particularly kV. Use cases for protective garments should be classified by typical procedural primary beam qualities, which are governed by the ADRC according to the impacts of patient size, anatomical location, and gantry angle. PMID- 27370134 TI - Recombination in liquid-filled ionization chambers beyond the Boag limit. AB - PURPOSE: The high mass density and low mobilities of charge carriers can cause important recombination in liquid-filled ionization chambers (LICs). Saturation correction methods have been proposed for LICs. Correction methods for pulsed irradiation are based on Boag equation. However, Boag equation assumes that the charge ionized by one pulse is fully collected before the arrival of the next pulse. This condition does not hold in many clinical beams where the pulse repetition period may be shorter than the charge collection time, causing overlapping between charge carriers ionized by different pulses, and Boag equation is not applicable there. In this work, the authors present an experimental and numerical characterization of collection efficiencies in LICs beyond the Boag limit, with overlapping between charge carriers ionized by different pulses. METHODS: The authors have studied recombination in a LIC array for different dose-per-pulse, pulse repetition frequency, and polarization voltage values. Measurements were performed in a Truebeam Linac using FF and FFF modalities. Dose-per-pulse and pulse repetition frequency have been obtained by monitoring the target current with an oscilloscope. Experimental collection efficiencies have been obtained by using a combination of the two-dose-rate method and ratios to the readout of a reference chamber (CC13, IBA). The authors have also used numerical simulation to complement the experimental data. RESULTS: The authors have found that overlap significantly increases recombination in LICs, as expected. However, the functional dependence of collection efficiencies on the dose-per-pulse does not change (a linear dependence has been observed in the near-saturation region for different degrees of overlapping, the same dependence observed in the nonoverlapping scenario). On the other hand, the dependence of collection efficiencies on the polarization voltage changes in the overlapping scenario and does not follow that of Boag equation, the reason being that changing the polarization voltage also affects the charge collection time, thus changing the amount of overlapping. CONCLUSIONS: These results have important consequences for saturation correction methods for LICs. On one hand, the two-dose-rate method, which relies on the functional dependence of the collection efficiencies on dose-per-pulse, can also be used in the overlapping situation, provided that the two measurements needed to feed the method are performed at the same pulse repetition frequency (monitor unit rate). This result opens the door to computing collection efficiencies in LICs in many clinical setups where charge overlap in the LIC exists. On the other hand, correction methods based on the voltage-dependence of Boag equation like the three-voltage method or the modified two-voltage method will not work in the overlapping scenario due to the different functional dependence of collection efficiencies on the polarization voltage. PMID- 27370135 TI - Dual ring multilayer ionization chamber and theory-based correction technique for scanning proton therapy. AB - PURPOSE: To develop a multilayer ionization chamber (MLIC) and a correction technique that suppresses differences between the MLIC and water phantom measurements in order to achieve fast and accurate depth dose measurements in pencil beam scanning proton therapy. METHODS: The authors distinguish between a calibration procedure and an additional correction: 1-the calibration for variations in the air gap thickness and the electrometer gains is addressed without involving measurements in water; 2-the correction is addressed to suppress the difference between depth dose profiles in water and in the MLIC materials due to the nuclear interaction cross sections by a semiempirical model tuned by using measurements in water. In the correction technique, raw MLIC data are obtained for each energy layer and integrated after multiplying them by the correction factor because the correction factor depends on incident energy. The MLIC described here has been designed especially for pencil beam scanning proton therapy. This MLIC is called a dual ring multilayer ionization chamber (DRMLIC). The shape of the electrodes allows the DRMLIC to measure both the percentage depth dose (PDD) and integrated depth dose (IDD) because ionization electrons are collected from inner and outer air gaps independently. RESULTS: IDDs for which the beam energies were 71.6, 120.6, 159, 180.6, and 221.4 MeV were measured and compared with water phantom results. Furthermore, the measured PDDs along the central axis of the proton field with a nominal field size of 10 * 10 cm(2) were compared. The spread out Bragg peak was 20 cm for fields with a range of 30.6 and 3 cm for fields with a range of 6.9 cm. The IDDs measured with the DRMLIC using the correction technique were consistent with those that of the water phantom; except for the beam energy of 71.6 MeV, all of the points satisfied the 1% dose/1 mm distance to agreement criterion of the gamma index. The 71.6 MeV depth dose profile showed slight differences in the shallow region, but 94.5% of the points satisfied the 1%/1 mm criterion. The 90% ranges, defined at the 90% dose position in distal fall off, were in good agreement with those in the water phantom, and the range differences from the water phantom were less than +/-0.3 mm. The PDDs measured with the DRMLIC were also consistent with those that of the water phantom; 97% of the points passed the 1%/1 mm criterion. CONCLUSIONS: It was demonstrated that the new correction technique suppresses the difference between the depth dose profiles obtained with the MLIC and those obtained from a water phantom, and a DRMLIC enabling fast measurements of both IDD and PDD was developed. The IDDs and PDDs measured with the DRMLIC and using the correction technique were in good agreement with those that of the water phantom, and it was concluded that the correction technique and DRMLIC are useful for depth dose profile measurements in pencil beam scanning proton therapy. PMID- 27370136 TI - Investigation of practical initial attenuation image estimates in TOF-MLAA reconstruction for PET/MR. AB - PURPOSE: Time-of-flight joint attenuation and activity positron emission tomography reconstruction requires additional calibration (scale factors) or constraints during or post-reconstruction to produce a quantitative MU-map. In this work, the impact of various initializations of the joint reconstruction was investigated, and the initial average mu-value (IAM) method was introduced such that the forward-projection of the initial MU-map is already very close to that of the reference MU-map, thus reducing/minimizing the offset (scale factor) during the early iterations of the joint reconstruction. Consequently, the accuracy and efficiency of unconstrained joint reconstruction such as time-of flight maximum likelihood estimation of attenuation and activity (TOF-MLAA) can be improved by the proposed IAM method. METHODS: 2D simulations of brain and chest were used to evaluate TOF-MLAA with various initial estimates which include the object filled with water uniformly (conventional initial estimate), bone uniformly, the average MU-value uniformly (IAM magnitude initialization method), and the perfect spatial MU-distribution but with a wrong magnitude (initialization in terms of distribution). 3D gate simulation was also performed for the chest phantom under a typical clinical scanning condition, and the simulated data were reconstructed with a fully corrected list-mode TOF-MLAA algorithm with various initial estimates. The accuracy of the average MU-values within the brain, chest, and abdomen regions obtained from the MR derived MU-maps was also evaluated using computed tomography MU-maps as the gold-standard. RESULTS: The estimated MU-map with the initialization in terms of magnitude (i.e., average MU-value) was observed to reach the reference more quickly and naturally as compared to all other cases. Both 2D and 3D gate simulations produced similar results, and it was observed that the proposed IAM approach can produce quantitative MU-map/emission when the corrections for physical effects such as scatter and randoms were included. The average MU-value obtained from MR derived MU-map was accurate within 5% with corrections for bone, fat, and uniform lungs. CONCLUSIONS: The proposed IAM-TOF-MLAA can produce quantitative MU-map without any calibration provided that there are sufficient counts in the measured data. For low count data, noise reduction and additional regularization/rescaling techniques need to be applied and investigated. The average MU-value within the object is prior information which can be extracted from MR and patient database, and it is feasible to obtain accurate average MU-value using MR derived MU-map with corrections as demonstrated in this work. PMID- 27370137 TI - Bone-marrow densitometry: Assessment of marrow space of human vertebrae by single energy high resolution-quantitative computed tomography. AB - PURPOSE: Accurate noninvasive assessment of vertebral bone marrow fat fraction is important for diagnostic assessment of a variety of disorders and therapies known to affect marrow composition. Moreover, it provides a means to correct fat induced bias of single energy quantitative computed tomography (QCT) based bone mineral density (BMD) measurements. The authors developed new segmentation and calibration methods to obtain quantitative surrogate measures of marrow-fat density in the axial skeleton. METHODS: The authors developed and tested two high resolution-QCT (HR-QCT) based methods which permit segmentation of bone voids in between trabeculae hypothesizing that they are representative of bone marrow space. The methods permit calculation of marrow content in units of mineral equivalent marrow density (MeMD). The first method is based on global thresholding and peeling (GTP) to define a volume of interest away from the transition between trabecular bone and marrow. The second method, morphological filtering (MF), uses spherical elements of different radii (0.1-1.2 mm) and automatically places them in between trabeculae to identify regions with large trabecular interspace, the bone-void space. To determine their performance, data were compared ex vivo to high-resolution peripheral CT (HR-pQCT) images as the gold-standard. The performance of the methods was tested on a set of excised human vertebrae with intact bone marrow tissue representative of an elderly population with low BMD. RESULTS: 86% (GTP) and 87% (MF) of the voxels identified as true marrow space on HR-pQCT images were correctly identified on HR-QCT images and thus these volumes of interest can be considered to be representative of true marrow space. Within this volume, MeMD was estimated with residual errors of 4.8 mg/cm(3) corresponding to accuracy errors in fat fraction on the order of 5% both for GTP and MF methods. CONCLUSIONS: The GTP and MF methods on HR-QCT images permit noninvasive localization and densitometric assessment of marrow fat with residual accuracy errors sufficient to study disorders and therapies known to affect bone marrow composition. Additionally, the methods can be used to correct BMD for fat induced bias. Application and testing in vivo and in longitudinal studies are warranted to determine the clinical performance and value of these methods. PMID- 27370138 TI - Endoluminal ultrasound applicators for MR-guided thermal ablation of pancreatic tumors: Preliminary design and evaluation in a porcine pancreas model. AB - PURPOSE: Endoluminal ultrasound may serve as a minimally invasive option for delivering thermal ablation to pancreatic tumors adjacent to the stomach or duodenum. The objective of this study was to explore the basic feasibility of this treatment strategy through the design, characterization, and evaluation of proof-of-concept endoluminal ultrasound applicators capable of placement in the gastrointestinal (GI) lumen for volumetric pancreas ablation under MR guidance. METHODS: Two variants of the endoluminal applicator, each containing a distinct array of two independently powered transducers (10 * 10 mm 3.2 MHz planar; or 8 * 10 * 20 mm radius of curvature 3.3 MHz curvilinear geometries) at the distal end of a meter long flexible catheter assembly, were designed and fabricated. Transducers and circulatory water flow for acoustic coupling and luminal cooling were contained by a low-profile polyester balloon covering the transducer assembly fixture. Each applicator incorporated miniature spiral MR coils and mechanical features (guiding tips and hinges) to facilitate tracking and insertion through the GI tract under MRI guidance. Acoustic characterization of each device was performed using radiation force balance and hydrophone measurements. Device delivery into the upper GI tract, adjacent to the pancreas, and heating characteristics for treatment of pancreatic tissue were evaluated in MR-guided ex vivo and in vivo porcine experiments. MR guidance was utilized for anatomical target identification, tracking/positioning of the applicator, and MR temperature imaging (MRTI) for PRF-based multislice thermometry, implemented in the real-time RTHawk software environment. RESULTS: Force balance and hydrophone measurements indicated efficiencies of 48.8% and 47.8% and -3 dB intensity beam widths of 3.2 and 1.2 mm for the planar and curvilinear transducers, respectively. Ex vivo studies on whole-porcine carcasses revealed capabilities of producing ablative temperature rise (DeltaT > 15 degrees C) contours in pancreatic tissue 4-40 mm long and 4-28 mm wide for the planar transducer applicator (1-13 min sonication duration, ~4 W/cm(2) applied acoustic intensity). Curvilinear transducers produced more selective heating, with a narrower DeltaT > 15 degrees C contour length and width of up to 1-24 mm and 2-7 mm, respectively (1-7 min sonication duration, ~4 W/cm(2) applied acoustic intensity). Active tracking of the miniature spiral coils was achieved using a Hadamard encoding tracking sequence, enabling real-time determination of each coil's coordinates and automated prescription of imaging planes for thermometry. In vivo MRTI-guided heating trials in three pigs demonstrated capability of ~20 degrees C temperature elevation in pancreatic tissue at 2 cm depths from the applicator, with 5-7 W/cm(2) applied intensity and 6-16 min sonication duration. Dimensions of thermal lesions in the pancreas ranged from 12 to 28 mm, 3 to 10 mm, and 5 to 10 mm in length, width, and depth, respectively, as verified through histological analysis of tissue sections. Multiple-baseline reconstruction and respiratory gated acquisition were demonstrated to be effective strategies in suppressing motion artifacts for clear evolution of temperature profiles during MRTI in the in vivo studies. CONCLUSIONS: This study demonstrates the technical feasibility of generating volumetric ablation in pancreatic tissue using endoluminal ultrasound applicators positioned in the stomach lumen. MR guidance facilitates target identification, device tracking/positioning, and treatment monitoring through real-time multislice PRF-based thermometry. PMID- 27370139 TI - Ion recombination correction in carbon ion beams. AB - PURPOSE: In this work, ion recombination is studied as a function of energy and depth in carbon ion beams. METHODS: Measurements were performed in three different passively scattered carbon ion beams with energies of 62 MeV/n, 135 MeV/n, and 290 MeV/n using various types of plane-parallel ionization chambers. Experimental results were compared with two analytical models for initial recombination. One model is generally used for photon beams and the other model, developed by Jaffe, takes into account the ionization density along the ion track. An investigation was carried out to ascertain the effect on the ion recombination correction with varying ionization chamber orientation with respect to the direction of the ion tracks. The variation of the ion recombination correction factors as a function of depth was studied for a Markus ionization chamber in the 62 MeV/n nonmodulated carbon ion beam. This variation can be related to the depth distribution of linear energy transfer. RESULTS: Results show that the theory for photon beams is not applicable to carbon ion beams. On the other hand, by optimizing the value of the ionization density and the initial mean-square radius, good agreement is found between Jaffe's theory and the experimental results. As predicted by Jaffe's theory, the results confirm that ion recombination corrections strongly decrease with an increasing angle between the ion tracks and the electric field lines. For the Markus ionization chamber, the variation of the ion recombination correction factor with depth was modeled adequately by a sigmoid function, which is approximately constant in the plateau and strongly increasing in the Bragg peak region to values of up to 1.06. Except in the distal edge region, all experimental results are accurately described by Jaffe's theory. CONCLUSIONS: Experimental results confirm that ion recombination in the investigated carbon ion beams is dominated by initial recombination. Ion recombination corrections are found to be significant and cannot be neglected for reference dosimetry and for the determination of depth dose curves in carbon ion beams. PMID- 27370141 TI - A comprehensive formulation for volumetric modulated arc therapy planning. AB - PURPOSE: Volumetric modulated arc therapy (VMAT) is a widely employed radiation therapy technique, showing comparable dosimetry to static beam intensity modulated radiation therapy (IMRT) with reduced monitor units and treatment time. However, the current VMAT optimization has various greedy heuristics employed for an empirical solution, which jeopardizes plan consistency and quality. The authors introduce a novel direct aperture optimization method for VMAT to overcome these limitations. METHODS: The comprehensive VMAT (comVMAT) planning was formulated as an optimization problem with an L2-norm fidelity term to penalize the difference between the optimized dose and the prescribed dose, as well as an anisotropic total variation term to promote piecewise continuity in the fluence maps, preparing it for direct aperture optimization. A level set function was used to describe the aperture shapes and the difference between aperture shapes at adjacent angles was penalized to control MLC motion range. A proximal-class optimization solver was adopted to solve the large scale optimization problem, and an alternating optimization strategy was implemented to solve the fluence intensity and aperture shapes simultaneously. Single arc comVMAT plans, utilizing 180 beams with 2 degrees angular resolution, were generated for a glioblastoma multiforme case, a lung (LNG) case, and two head and neck cases-one with three PTVs (H&N3PTV) and one with foue PTVs (H&N4PTV)-to test the efficacy. The plans were optimized using an alternating optimization strategy. The plans were compared against the clinical VMAT (clnVMAT) plans utilizing two overlapping coplanar arcs for treatment. RESULTS: The optimization of the comVMAT plans had converged within 600 iterations of the block minimization algorithm. comVMAT plans were able to consistently reduce the dose to all organs-at-risk (OARs) as compared to the clnVMAT plans. On average, comVMAT plans reduced the max and mean OAR dose by 6.59% and 7.45%, respectively, of the prescription dose. Reductions in max dose and mean dose were as high as 14.5 Gy in the LNG case and 15.3 Gy in the H&N3PTV case. PTV coverages measured by D95, D98, and D99 were within 0.25% of the prescription dose. By comprehensively optimizing all beams, the comVMAT optimizer gained the freedom to allow some selected beams to deliver higher intensities, yielding a dose distribution that resembles a static beam IMRT plan with beam orientation optimization. CONCLUSIONS: The novel nongreedy VMAT approach simultaneously optimizes all beams in an arc and then directly generates deliverable apertures. The single arc VMAT approach thus fully utilizes the digital Linac's capability in dose rate and gantry rotation speed modulation. In practice, the new single VMAT algorithm generates plans superior to existing VMAT algorithms utilizing two arcs. PMID- 27370142 TI - Three-dimensional quadratic modeling and quantitative evaluation of the diaphragm on a volumetric CT scan in patients with chronic obstructive pulmonary disease. AB - PURPOSE: In patients with chronic obstructive pulmonary disease (COPD), diaphragm function may deteriorate due to reduced muscle fiber length. Quantitative analysis of the morphology of the diaphragm is therefore important. In the authors current study, they propose a diaphragm segmentation method for COPD patients that uses volumetric chest computed tomography (CT) data, and they provide a quantitative analysis of the diaphragmatic dimensions. METHODS: Volumetric CT data were obtained from 30 COPD patients and 10 normal control patients using a 16-row multidetector CT scanner (Siemens Sensation 16) with 0.75 mm collimation. Diaphragm segmentation using 3D ray projections on the lower surface of the lungs was performed to identify the draft diaphragmatic lung surface, which was modeled using quadratic 3D surface fitting and robust regression in order to minimize the effects of segmentation error and parameterize diaphragm morphology. This result was visually evaluated by an expert thoracic radiologist. To take into consideration the shape features of the diaphragm, several quantification parameters-including the shape index on the apex (SIA) (which was computed using gradient set to 0), principal curvatures on the apex on the fitted diaphragm surface (CA), the height between the apex and the base plane (H), the diaphragm lengths along the x-, y-, and z-axes (XL, YL, ZL), quadratic-fitted diaphragm lengths on the z-axis (FZL), average curvature (C), and surface area (SA)-were measured using in-house software and compared with the pulmonary function test (PFT) results. RESULTS: The overall accuracy of the combined segmentation method was 97.22% +/- 4.44% while the visual accuracy of the models for the segmented diaphragms was 95.28% +/- 2.52% (mean +/- SD). The quantitative parameters, including SIA, CA, H, XL, YL, ZL, FZL, C, and SA were 0.85 +/- 0.05 (mm(-1)), 0.01 +/- 0.00 (mm(-1)), 17.93 +/- 10.78 (mm), 129.80 +/- 11.66 (mm), 163.19 +/- 13.45 (mm), 71.27 +/- 17.52 (mm), 61.59 +/- 16.98 (mm), 0.01 +/- 0.00 (mm(-1)), and 34 380.75 +/- 6680.06 (mm(2)), respectively. Several parameters were correlated with the PFT parameters. CONCLUSIONS: The authors propose an automatic method for quantitatively evaluating the morphological parameters of the diaphragm on volumetric chest CT in COPD patients. By measuring not only the conventional length and surface area but also the shape features of the diaphragm using quadratic 3D surface modeling, the proposed method is especially useful for quantifying diaphragm characteristics. Their method may be useful for assessing morphological diaphragmatic changes in COPD patients. PMID- 27370140 TI - The report of Task Group 100 of the AAPM: Application of risk analysis methods to radiation therapy quality management. AB - The increasing complexity of modern radiation therapy planning and delivery challenges traditional prescriptive quality management (QM) methods, such as many of those included in guidelines published by organizations such as the AAPM, ASTRO, ACR, ESTRO, and IAEA. These prescriptive guidelines have traditionally focused on monitoring all aspects of the functional performance of radiotherapy (RT) equipment by comparing parameters against tolerances set at strict but achievable values. Many errors that occur in radiation oncology are not due to failures in devices and software; rather they are failures in workflow and process. A systematic understanding of the likelihood and clinical impact of possible failures throughout a course of radiotherapy is needed to direct limit QM resources efficiently to produce maximum safety and quality of patient care. Task Group 100 of the AAPM has taken a broad view of these issues and has developed a framework for designing QM activities, based on estimates of the probability of identified failures and their clinical outcome through the RT planning and delivery process. The Task Group has chosen a specific radiotherapy process required for "intensity modulated radiation therapy (IMRT)" as a case study. The goal of this work is to apply modern risk-based analysis techniques to this complex RT process in order to demonstrate to the RT community that such techniques may help identify more effective and efficient ways to enhance the safety and quality of our treatment processes. The task group generated by consensus an example quality management program strategy for the IMRT process performed at the institution of one of the authors. This report describes the methodology and nomenclature developed, presents the process maps, FMEAs, fault trees, and QM programs developed, and makes suggestions on how this information could be used in the clinic. The development and implementation of risk assessment techniques will make radiation therapy safer and more efficient. PMID- 27370143 TI - Characterization of a synthetic single crystal diamond detector for dosimetry in spatially fractionated synchrotron x-ray fields. AB - PURPOSE: Modern radiotherapy modalities often use small or nonstandard fields to ensure highly localized and precise dose delivery, challenging conventional clinical dosimetry protocols. The emergence of preclinical spatially fractionated synchrotron radiotherapies with high dose-rate, sub-millimetric parallel kilovoltage x-ray beams, has pushed clinical dosimetry to its limit. A commercially available synthetic single crystal diamond detector designed for small field dosimetry has been characterized to assess its potential as a dosimeter for synchrotron microbeam and minibeam radiotherapy. METHODS: Experiments were carried out using a synthetic diamond detector on the imaging and medical beamline (IMBL) at the Australian Synchrotron. The energy dependence of the detector was characterized by cross-referencing with a calibrated ionization chamber in monoenergetic beams in the energy range 30-120 keV. The dose-rate dependence was measured in the range 1-700 Gy/s. Dosimetric quantities were measured in filtered white beams, with a weighted mean energy of 95 keV, in broadbeam and spatially fractionated geometries, and compared to reference dosimeters. RESULTS: The detector exhibits an energy dependence; however, beam quality correction factors (kQ) have been measured for energies in the range 30 120 keV. The kQ factor for the weighted mean energy of the IMBL radiotherapy spectrum, 95 keV, is 1.05 +/- 0.09. The detector response is independent of dose rate in the range 1-700 Gy/s. The percentage depth dose curves measured by the diamond detector were compared to ionization chambers and agreed to within 2%. Profile measurements of microbeam and minibeam arrays were performed. The beams are well resolved and the full width at halfmaximum agrees with the nominal width of the beams. The peak to valley dose ratio (PVDR) calculated from the profiles at various depths in water agrees within experimental error with PVDR calculations from Gafchromic film data. CONCLUSIONS: The synthetic diamond detector is now well characterized and will be used to develop an experimental dosimetry protocol for spatially fractionated synchrotron radiotherapy. PMID- 27370144 TI - SIS epidemiological model for adaptive RT: Forecasting the parotid glands shrinkage during tomotherapy treatment. AB - PURPOSE: A susceptible-infected-susceptible (SIS) epidemic model was applied to radiation therapy (RT) treatments to predict morphological variations in head and neck (H&N) anatomy. METHODS: 360 daily MVCT images of 12 H&N patients treated by tomotherapy were analyzed in this retrospective study. Deformable image registration (DIR) algorithms, mesh grids, and structure recontouring, implemented in the RayStation treatment planning system (TPS), were applied to assess the daily organ warping. The parotid's warping was evaluated using the epidemiological approach considering each vertex as a single subject and its deformed vector field (DVF) as an infection. Dedicated IronPython scripts were developed to export daily coordinates and displacements of the region of interest (ROI) from the TPS. matlab tools were implemented to simulate the SIS modeling. Finally, the fully trained model was applied to a new patient. RESULTS: A QUASAR phantom was used to validate the model. The patients' validation was obtained setting 0.4 cm of vertex displacement as threshold and splitting susceptible (S) and infectious (I) cases. The correlation between the epidemiological model and the parotids' trend for further optimization of alpha and beta was carried out by Euclidean and dynamic time warping (DTW) distances. The best fit with experimental conditions across all patients (Euclidean distance of 4.09 +/- 1.12 and DTW distance of 2.39 +/- 0.66) was obtained setting the contact rate at 7.55 +/- 0.69 and the recovery rate at 2.45 +/- 0.26; birth rate was disregarded in this constant population. CONCLUSIONS: Combining an epidemiological model with adaptive RT (ART), the authors' novel approach could support image-guided radiation therapy (IGRT) to validate daily setup and to forecast anatomical variations. The SIS-ART model developed could support clinical decisions in order to optimize timing of replanning achieving personalized treatments. PMID- 27370145 TI - Evaluation of a tissue-mimicking thermochromic phantom for radiofrequency ablation. AB - PURPOSE: This work describes the characterization and evaluation of a tissue mimicking thermochromic phantom (TMTCP) for direct visualization and quantitative determination of temperatures during radiofrequency ablation (RFA). METHODS: TMTCP material was prepared using polyacrylamide gel and thermochromic ink that permanently changes color from white to magenta when heated. Color vs temperature calibration was generated in matlab by extracting RGB color values from digital photographs of phantom standards heated in a water bath at 25-75 degrees C. RGB and temperature values were plotted prior to curve fitting in mathematica using logistic functions of form f(t) = a + b/(1 + e((c(t-d)))), where a, b, c, and d are coefficients and t denotes temperature. To quantify temperatures based on TMTCP color, phantom samples were heated to temperatures blinded to the investigators, and two methods were evaluated: (1) visual comparison of sample color to the calibration series and (2) in silico analysis using the inverse of the logistic functions to convert sample photograph RGB values to absolute temperatures. For evaluation of TMTCP performance with RFA, temperatures in phantom samples and in a bovine liver were measured radially from an RF electrode during heating using fiber-optic temperature probes. Heating and cooling rates as well as the area under the temperature vs time curves were compared. Finally, temperature isotherms were generated computationally based on color change in bisected phantoms following RFA and compared to temperature probe measurements. RESULTS: TMTCP heating resulted in incremental, permanent color changes between 40 and 64 degrees C. Visual and computational temperature estimation methods were accurate to within 1.4 and 1.9 degrees C between 48 and 67 degrees C, respectively. Temperature estimates were most accurate between 52 and 62 degrees C, resulting in differences from actual temperatures of 0.6 and 1.6 degrees C for visual and computational methods, respectively. Temperature measurements during RFA using fiber-optic probes matched closely with maximum temperatures predicted by color changes in the TMTCP. Heating rate and cooling rate, as well as the area under the temperature vs time curve were similar for TMTCP and ex vivo liver. CONCLUSIONS: The TMTCP formulated for use with RFA can be used to provide quantitative temperature information in mild hyperthermic (40-45 degrees C), subablative (45-50 degrees C), and ablative (>50 degrees C) temperature ranges. Accurate visual or computational estimates of absolute temperatures and ablation zone geometry can be made with high spatial resolution based on TMTCP color. As such, the TMTCP can be used to assess RFA heating characteristics in a controlled, predictable environment. PMID- 27370146 TI - Effect of pulse sequence parameter selection on signal strength in positive contrast MRI markers for MRI-based prostate postimplant assessment. AB - PURPOSE: For postimplant dosimetric assessment, computed tomography (CT) is commonly used to identify prostate brachytherapy seeds, at the expense of accurate anatomical contouring. Magnetic resonance imaging (MRI) is superior to CT for anatomical delineation, but identification of the negative-contrast seeds is challenging. Positive-contrast MRI markers were proposed to replace spacers to assist seed localization on MRI images. Visualization of these markers under varying scan parameters was investigated. METHODS: To simulate a clinical scenario, a prostate phantom was implanted with 66 markers and 86 seeds, and imaged on a 3.0T MRI scanner using a 3D fast radiofrequency-spoiled gradient recalled echo acquisition with various combinations of scan parameters. Scan parameters, including flip angle, number of excitations, bandwidth, field-of view, slice thickness, and encoding steps were systematically varied to study their effects on signal, noise, scan time, image resolution, and artifacts. RESULTS: The effects of pulse sequence parameter selection on the marker signal strength and image noise were characterized. The authors also examined the tradeoff between signal-to-noise ratio, scan time, and image artifacts, such as the wraparound artifact, susceptibility artifact, chemical shift artifact, and partial volume averaging artifact. Given reasonable scan time and managable artifacts, the authors recommended scan parameter combinations that can provide robust visualization of the MRI markers. CONCLUSIONS: The recommended MRI pulse sequence protocol allows for consistent visualization of the markers to assist seed localization, potentially enabling MRI-only prostate postimplant dosimetry. PMID- 27370147 TI - A mathematical framework for virtual IMRT QA using machine learning. AB - PURPOSE: It is common practice to perform patient-specific pretreatment verifications to the clinical delivery of IMRT. This process can be time consuming and not altogether instructive due to the myriad sources that may produce a failing result. The purpose of this study was to develop an algorithm capable of predicting IMRT QA passing rates a priori. METHODS: From all treatment, 498 IMRT plans sites were planned in eclipse version 11 and delivered using a dynamic sliding window technique on Clinac iX or TrueBeam Linacs. 3%/3 mm local dose/distance-to-agreement (DTA) was recorded using a commercial 2D diode array. Each plan was characterized by 78 metrics that describe different aspects of their complexity that could lead to disagreements between the calculated and measured dose. A Poisson regression with Lasso regularization was trained to learn the relation between the plan characteristics and each passing rate. RESULTS: Passing rates 3%/3 mm local dose/DTA can be predicted with an error smaller than 3% for all plans analyzed. The most important metrics to describe the passing rates were determined to be the MU factor (MU per Gy), small aperture score, irregularity factor, and fraction of the plan delivered at the corners of a 40 * 40 cm field. The higher the value of these metrics, the worse the passing rates. CONCLUSIONS: The Virtual QA process predicts IMRT passing rates with a high likelihood, allows the detection of failures due to setup errors, and it is sensitive enough to detect small differences between matched Linacs. PMID- 27370148 TI - 4D-CT scans reveal reduced magnitude of respiratory liver motion achieved by different abdominal compression plate positions in patients with intrahepatic tumors undergoing helical tomotherapy. AB - PURPOSE: While abdominal compression (AC) can be used to reduce respiratory liver motion in patients receiving helical tomotherapy for hepatocellular carcinoma, the nature and extent of this effect is not well described. The purpose of this study was to evaluate the changes in magnitude of three-dimensional liver motion with abdominal compression using four-dimensional (4D) computed tomography (CT) images of several plate positions. METHODS: From January 2012 to October 2015, 72 patients with intrahepatic carcinoma and divided into four groups underwent 4D-CT scans to assess respiratory liver motion. Of the 72 patients, 19 underwent abdominal compression of the cephalic area between the subxiphoid and umbilicus (group A), 16 underwent abdominal compression of the caudal region between the subxiphoid area and the umbilicus (group B), 11 patients underwent abdominal compression of the caudal umbilicus (group C), and 26 patients remained free breathing (group D). 4D-CT images were sorted into ten-image series, according to the respiratory phase from the end inspiration to the end expiration, and then transferred to treatment planning software. All liver contours were drawn by a single physician and confirmed by a second physician. Liver relative coordinates were automatically generated to calculate the liver respiratory motion in different axial directions to compile the 10 ten contours into a single composite image. Differences in respiratory liver motion were assessed with a one-way analysis of variance test of significance. RESULTS: The average respiratory liver motion in the Y axial direction was 4.53 +/- 1.16, 7.56 +/- 1.30, 9.95 +/- 2.32, and 9.53 +/- 2.62 mm in groups A, B, C, and D, respectively, with a significant change among the four groups (p < 0.001). Abdominal compression was most effective in group A (compression plate on the subxiphoid area), with liver displacement being 2.53 +/- 0.93, 4.53 +/- 1.16, and 2.14 +/- 0.92 mm on the X-, Y-, and Z-axes, respectively. There was no significant difference in respiratory liver motion between group C (displacement: 3.23 +/- 1.47, 9.95 +/- 2.32, and 2.92 +/- 1.10 mm on the X-, Y-, and Z-axes, respectively) and group D (displacement: 3.35 +/- 1.55, 9.53 +/- 2.62, and 3.35 +/- 1.73 mm on the X-, Y-, and Z-axes, respectively). Abdominal compression was least effective in group C (compression on caudal umbilicus), with liver motion in this group similar to that of free-breathing patients (group D). CONCLUSIONS: 4D-CT scans revealed significant liver motion control via abdominal compression of the subxiphoid area; however, this control of liver motion was not observed with compression of the caudal umbilicus. The authors, therefore, recommend compression of the subxiphoid area in patients undergoing external radiotherapy for intrahepatic carcinoma. PMID- 27370149 TI - Prospective treatment plan-specific action limits for real-time intrafractional monitoring in surface image guided radiosurgery. AB - PURPOSE: In surface image guided radiosurgery, action limits are created to determine at what point intrafractional motion exhibited by the patient is large enough to warrant intervention. Action limit values remain constant across patients despite the fact that patient motion affects the target coverage of brain metastases differently depending on the planning technique and other treatment plan-specific factors. The purpose of this work was twofold. The first purpose was to characterize the sensitivity of single-met per iso and multimet per iso treatment plans to uncorrected patient motion. The second purpose was to describe a method to prospectively determine treatment plan-specific action limits considering this sensitivity. METHODS: In their surface image guided radiosurgery technique, patient positioning is achieved with a thermoplastic mask that does not cover the patient's face. The patient's exposed face is imaged by a stereoscopic photogrammetry system. It is then compared to a reference surface and monitored throughout treatment. Seventy-two brain metastases (representing 29 patients) were used for this study. Twenty-five mets were treated individually ("single-met per iso plans"), and 47 were treated in a plan simultaneously with at least one other met ("multimet per iso plans"). For each met, the proportion of the gross tumor volume that remained within the 100% prescription isodose line was estimated under the influence of combinations of translations and rotations (0.0-3.0 mm and 0.0 degrees -3.0 degrees , respectively). The target volume and the prescription dose-volume were considered concentric spheres that each encompassed a volume determined from the treatment plan. Plan-specific contour plots and DVHs were created to illustrate the sensitivity of a specific lesion to uncorrected patient motion. RESULTS: Both single-met per iso and multimet per iso plans exhibited compromised target coverage under translations and rotations, though multimet per iso plans were considerably more sensitive to these transformations (2.3% and 39.8%, respectively). Plan-specific contour plots and DVHs were used to illustrate how size, distance from isocenter, and planning technique affect a particular met's sensitivity to motion. CONCLUSIONS: Stereotactic radiosurgery treatment plans that treat multiple brain metastases using a common isocenter are particularly susceptible to compromised target coverage as a result of uncorrected patient motion. The use of such a planning technique along with other treatment plan-specific factors should influence patient motion management. A graphical representation of the effect of translations and rotations on any particular plan can be generated to inform clinicians of the appropriate action limit when monitoring intrafractional motion. PMID- 27370150 TI - A mouse radiation-induced liver disease model for stereotactic body radiation therapy validated in patients with hepatocellular carcinoma. AB - PURPOSE: Lower radiation tolerance of the whole liver hinders dose escalations of stereotactic body radiation therapy (SBRT) in hepatocellular carcinoma (HCC) treatment. This study was conducted to define the exact doses that result in radiation-induced liver disease (RILD) as well as to determine dose constraints for the critical organs at risk (OARs) in mice; these parameters are still undefined in HCC SBRT. METHODS: This study consisted of two phases. In the primary phase, mice treated with helical tomotherapy-based SBRT were stratified according to escalating radiation doses to the livers. The pathological differences, signs [such as mouse performance status (MPS)], and serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/albumin levels were observed. Radiation-induced disease severities of the OARs were scored using systematic evaluation standards. In the validation phase in humans, 13 patients with HCC who had undergone radiotherapy before hepatectomy were enrolled to validate RILD pathological changes in a mouse study. RESULTS: The evaluation criteria of the mouse liver radiotherapy-related signs were as follows: MPS >= 2.0 +/- 0.52, AST/ALT >= 589.2 +/- 118.5/137.4 +/- 15.3 U/L, serum albumin <= 16.8 +/- 2.29 g/L. The preliminary dose constraints of the OARs were also obtained, such as those for the liver (average dose <= 26.36 +/- 1.71 Gy) and gastrointestinal tract (maximum dose <= 22.63 Gy). Mouse RILD models were able to be developed when the livers were irradiated with average doses of >=31.76 +/- 1.94 Gy (single fraction). RILD pathological changes in mice have also been validated in HCC patients. CONCLUSIONS: Mouse RILD models could be developed with SBRT based on the dose constraints for the OARs and evaluation criteria of mouse liver radiotherapy-related signs, and the authors' results favor the study of further approaches to treat HCC with SBRT. PMID- 27370151 TI - Mediastinal lymph node detection and station mapping on chest CT using spatial priors and random forest. AB - PURPOSE: To develop an automated system for mediastinal lymph node detection and station mapping for chest CT. METHODS: The contextual organs, trachea, lungs, and spine are first automatically identified to locate the region of interest (ROI) (mediastinum). The authors employ shape features derived from Hessian analysis, local object scale, and circular transformation that are computed per voxel in the ROI. Eight more anatomical structures are simultaneously segmented by multiatlas label fusion. Spatial priors are defined as the relative multidimensional distance vectors corresponding to each structure. Intensity, shape, and spatial prior features are integrated and parsed by a random forest classifier for lymph node detection. The detected candidates are then segmented by the following curve evolution process. Texture features are computed on the segmented lymph nodes and a support vector machine committee is used for final classification. For lymph node station labeling, based on the segmentation results of the above anatomical structures, the textual definitions of mediastinal lymph node map according to the International Association for the Study of Lung Cancer are converted into patient-specific color-coded CT image, where the lymph node station can be automatically assigned for each detected node. RESULTS: The chest CT volumes from 70 patients with 316 enlarged mediastinal lymph nodes are used for validation. For lymph node detection, their system achieves 88% sensitivity at eight false positives per patient. For lymph node station labeling, 84.5% of lymph nodes are correctly assigned to their stations. CONCLUSIONS: Multiple-channel shape, intensity, and spatial prior features aggregated by a random forest classifier improve mediastinal lymph node detection on chest CT. Using the location information of segmented anatomic structures from the multiatlas formulation enables accurate identification of lymph node stations. PMID- 27370152 TI - 2D radially compensating excitation pulse in combination with an internal transceiver antenna for 3D MRI of the rectum at 7 T. AB - PURPOSE: The high precession frequency in ultrahigh field MRI coincides with reduced RF penetration, increased RF power deposition and consequently can lead to reduced scan efficiency. However, the shorter wavelength enables the use of efficient antennas rather than loop coils. In fact, ultrathin monopole antennas have been demonstrated at 7 T, which fit in natural cavities like the rectum in the human body. As the RF field generated by the antenna provides an extremely nonuniform B1 field, the use of conventional RF pulses will lead to severe image distortions and highly nonuniform contrast. However, using the two predominant dimensions (orthogonal to the antenna), 2D RF pulses can be designed that counteract the nonuniform B1 into uniform flip angles. In this study the authors investigate the use of an ultrathin antenna not only for reception, but also for transmission in 7 T MRI of the rectum. METHODS: The 2D radially compensating excitation (2D RACE) pulse was designed in matlab. SAR calculations between the 2D RACE pulse and an adiabatic RF pulse (BIR-4) have been obtained, to visualize the gain in decreasing the SAR when using the 2D RACE pulse instead of an adiabatic RF pulse. The authors used the 7 T whole body MR system in combination with an internally placed monopole antenna used for transceiving and obtained 3D gradient echo images with a conventional sinc pulse and with the 2D RACE pulse. For extra clarity, they also reconstructed an image where the receive field of the antenna was removed. RESULTS: Comparing the results of the SAR simulations of the 2D RACE pulse with a BIR-4 pulse shows that for low flip angles (theta < 41 degrees ) the SAR can be decreased with a factor of 4.8 or even more, when using the 2D RACE pulse. Relative to a conventional sinc excitation, the 2D RACE pulse achieves more uniform flip angle distributions than a BIR-4 pulse with a smaller SAR increase (16 * versus 64 *). CONCLUSIONS: The authors have shown that the 2D RACE pulse provides more homogeneous flip angles for gradient echo sequences when compared to a conventional sinc pulse albeit at increased SAR. However, when compared to adiabatic RF pulses, as shown by simulations, the SAR of the 2D RACE pulse can be an order of magnitude less. Phantom and in vivo human rectum images are obtained to demonstrate that the 2D RACE pulse can provide a uniform excitation while transmitting with a single ultrathin endorectal antenna at 7 T. The combination of thin rectal antennas with efficient uniform transmit can open up new possibilities in high resolution imaging of rectal cancer. PMID- 27370154 TI - Robert J. Shalek, Ph.D., J.D. PMID- 27370153 TI - Heterodyne frequency-domain multispectral diffuse optical tomography of breast cancer in the parallel-plane transmission geometry. AB - PURPOSE: The authors introduce a state-of-the-art all-optical clinical diffuse optical tomography (DOT) imaging instrument which collects spatially dense, multispectral, frequency-domain breast data in the parallel-plate geometry. METHODS: The instrument utilizes a CCD-based heterodyne detection scheme that permits massively parallel detection of diffuse photon density wave amplitude and phase for a large number of source-detector pairs (10(6)). The stand-alone clinical DOT instrument thus offers high spatial resolution with reduced crosstalk between absorption and scattering. Other novel features include a fringe profilometry system for breast boundary segmentation, real-time data normalization, and a patient bed design which permits both axial and sagittal breast measurements. RESULTS: The authors validated the instrument using tissue simulating phantoms with two different chromophore-containing targets and one scattering target. The authors also demonstrated the instrument in a case study breast cancer patient; the reconstructed 3D image of endogenous chromophores and scattering gave tumor localization in agreement with MRI. CONCLUSIONS: Imaging with a novel parallel-plate DOT breast imager that employs highly parallel, high resolution CCD detection in the frequency-domain was demonstrated. PMID- 27370155 TI - Upper limits of the photon fluence rate on CT detectors: Case study on a commercial scanner. AB - PURPOSE: The highest photon fluence rate that a computed tomography (CT) detector must be able to measure is an important parameter. The authors calculate the maximum transmitted fluence rate in a commercial CT scanner as a function of patient size for standard head, chest, and abdomen protocols. METHODS: The authors scanned an anthropomorphic phantom (Kyoto Kagaku PBU-60) with the reference CT protocols provided by AAPM on a GE LightSpeed VCT scanner and noted the tube current applied with the tube current modulation (TCM) system. By rescaling this tube current using published measurements on the tube current modulation of a GE scanner [N. Keat, "CT scanner automatic exposure control systems," MHRA Evaluation Report 05016, ImPACT, London, UK, 2005], the authors could estimate the tube current that these protocols would have resulted in for other patient sizes. An ECG gated chest protocol was also simulated. Using measured dose rate profiles along the bowtie filters, the authors simulated imaging of anonymized patient images with a range of sizes on a GE VCT scanner and calculated the maximum transmitted fluence rate. In addition, the 99th and the 95th percentiles of the transmitted fluence rate distribution behind the patient are calculated and the effect of omitting projection lines passing just below the skin line is investigated. RESULTS: The highest transmitted fluence rates on the detector for the AAPM reference protocols with centered patients are found for head images and for intermediate-sized chest images, both with a maximum of 3.4 ? 10(8) mm(-2) s(-1), at 949 mm distance from the source. Miscentering the head by 50 mm downward increases the maximum transmitted fluence rate to 5.7 ? 10(8) mm(-2) s(-1). The ECG gated chest protocol gives fluence rates up to 2.3 ? 10(8) - 3.6 ? 10(8) mm(-2) s(-1) depending on miscentering. CONCLUSIONS: The fluence rate on a CT detector reaches 3 ? 10(8) - 6 ? 10(8) mm( 2) s(-1) in standard imaging protocols, with the highest rates occurring for ECG gated chest and miscentered head scans. These results will be useful to developers of CT detectors, in particular photon counting detectors. PMID- 27370156 TI - Interfractional variation in bladder volume and its impact on cervical cancer radiotherapy: Clinical significance of portable bladder scanner. AB - PURPOSE: A constant bladder volume (BV) is essential to direct the radiotherapy (RT) of pelvic tumors with precision. The purpose of this study was to investigate changes in BV and their impact on cervical cancer RT and to assess the clinical significance of a portable bladder scanner (BS) in achieving a constant BV. METHODS: A standard bladder phantom (133 ml) and measurements of actual urine volume were both used as benchmarks to evaluate the accuracy of the BS. Comparisons of BS with computed tomography (CT), cone-beam CT (CBCT), and an ultrasound diagnostic device (iU22) were made. Twenty-two consecutive patients with cervical cancer treated with external beam radical RT were divided into an experimental group (13 patients) and a control group (9 patients). In the experimental group, the BV was measured multiple times by BS pre-RT until it was consistent with that found by planning CT. Then a CBCT was performed. The BV was measured again immediately post-RT, after which the patient's urine was collected and recorded. In the control group, CBCT only was performed pre-RT. Interfractional changes in BV and their impact on cervical cancer RT were investigated in both groups. The time of bladder filling was also recorded and analyzed. RESULTS: In measuring the volume of the standard bladder phantom, the BS deviated by 1.4% in accuracy. The difference between the measurements of the BS and the iU22 had no statistical significance (linear correlation coefficient 0.96, P < 0.05). The BV measured by the BS was strongly correlated with the actual urine volume (R = 0.95, P < 0.05), planning CT (R = 0.95, P < 0.05), or CBCT (R = 0.91, P < 0.05). Compared with the BV at the time of CT, its value changed by -36.1% [1 SD (standard deviation) 42.3%; range, -79.1%-29.4%] in the control group, and 5.2% (1 SD 21.5%; range, -13.3%-22.1%) in the experimental group during treatment. The change in BV affected the target position in the superior-inferior (SI) direction but had little or no effect in the anterior posterior and right-left directions. Based on the collected data, the target displacement in the SI direction was reduced from 2.0 to 0.4 mm, while the CTV-to PTV (CTV: clinical target volume; PTV: planning target volume) margin in the SI direction was reduced from 11.1 to 6.4 mm. The BV increased by 3.7 +/- 1.0 ml/min (range, 1.7-4.7 ml/min), which depended on the amount of water ingested by the patient (R = 0.96, P < 0.05). No correlation was found between the rate of urinary inflow and the patient's body mass. The authors were able to reduce the workload of measuring by using individual patient information including the patient's age, the water-drinking amount, time at which water-drinking began, and patient's diet. CONCLUSIONS: Changes in the BV have an influence on the RT of cervical cancer. A consistent and reproducible BV is acquired by using a portable BS, whereby the target displacement and CTV-to-PTV margin can be both reduced in the SI direction. PMID- 27370157 TI - Four-dimensional dose reconstruction through in vivo phase matching of cine images of electronic portal imaging device. AB - PURPOSE: A method is proposed to reconstruct a four-dimensional (4D) dose distribution using phase matching of measured cine images to precalculated images of electronic portal imaging device (EPID). METHODS: (1) A phantom, designed to simulate a tumor in lung (a polystyrene block with a 3 cm diameter embedded in cork), was placed on a sinusoidally moving platform with an amplitude of 1 cm and a period of 4 s. Ten-phase 4D computed tomography (CT) images of the phantom were acquired. A planning target volume (PTV) was created by adding a margin of 1 cm around the internal target volume of the tumor. (2) Three beams were designed, which included a static beam, a theoretical dynamic beam, and a planning optimized dynamic beam (PODB). While the theoretical beam was made by manually programming a simplistic sliding leaf motion, the planning-optimized beam was obtained from treatment planning. From the three beams, three-dimensional (3D) doses on the phantom were calculated; 4D dose was calculated by means of the ten phase images (integrated over phases afterward); serving as "reference" images, phase-specific EPID dose images under the lung phantom were also calculated for each of the ten phases. (3) Cine EPID images were acquired while the beams were irradiated to the moving phantom. (4) Each cine image was phase-matched to a phase-specific CT image at which common irradiation occurred by intercomparing the cine image with the reference images. (5) Each cine image was used to reconstruct dose in the phase-matched CT image, and the reconstructed doses were summed over all phases. (6) The summation was compared with forwardly calculated 4D and 3D dose distributions. Accounting for realistic situations, intratreatment breathing irregularity was simulated by assuming an amplitude of 0.5 cm for the phantom during a portion of breathing trace in which the phase matching could not be performed. Intertreatment breathing irregularity between the time of treatment and the time of planning CT was considered by utilizing the same reduced amplitude when the phantom was irradiated. To examine the phase matching in a humanoid environment, the matching was also performed in a digital phantom (4D XCAT phantom). RESULTS: For the static, the theoretical, and the planning optimized dynamic beams, the 4D reconstructed doses showed agreement with the forwardly calculated 4D doses within the gamma pass rates of 92.7%, 100%, and 98.1%, respectively, at the isocenter plane given by 3%/3 mm criteria. Excellent agreement in dose volume histogram of PTV and lung-PTV was also found between the two 4D doses, while substantial differences were found between the 3D and the 4D doses. The significant breathing irregularities modeled in this study were found not to be noticeably affecting the reconstructed dose. The phase matching was performed equally well in a digital phantom. CONCLUSIONS: The method of retrospective phase determination of a moving object under irradiation provided successful 4D dose reconstruction. This method will provide accurate quality assurance and facilitate adaptive therapy when distinguishable objects such as well-defined tumors, diaphragm, and organs with markers (pancreas and liver) are covered by treatment beam apertures. PMID- 27370158 TI - Technical Note: A new phantom design for routine testing of Doppler ultrasound. AB - PURPOSE: The objective of this project is to demonstrate the principle and operation for a simple, inexpensive, and highly portable Doppler ultrasound quality assurance (QA) phantom intended for routine QA testing. A prototype phantom has been designed, fabricated, and evaluated. The phantom described here is powered by gravity alone, requires no external equipment for operation, and produces a stable fluid velocity useful for quality assurance. Many commercially available Doppler ultrasound testing systems can suffer from issues such as a lengthy setup, prohibitive cost, nonportable size, or difficulty in use. This new phantom design aims to address some of these problems and create a phantom appropriate for assessing Doppler ultrasound stability. METHODS: The phantom was fabricated using a 3D printer. The basic design of the phantom is to provide gravity-powered flow of a Doppler fluid between two reservoirs. The printed components were connected with latex tubing and then seated in a tissue mimicking gel. Spectral Doppler waveforms were sampled to evaluate variations in the data, and the phantom was evaluated using high frame rate video to find an alternate measure of mean fluid velocity flowing in the phantom. RESULTS: The current system design maintains stable flow from one reservoir to the other for approximately 7 s. Color Doppler imaging of the phantom was found to be qualitatively consistent with laminar flow. Using pulsed spectral Doppler, the average fluid velocity from a sample volume approximately centered in the synthetic vessel was measured to be 56 cm/s with a standard deviation of 3.2 cm/s across 118 measurements. An independent measure of the average fluid velocity was measured to be 51.9 cm/s with a standard deviation of 0.7 cm/s over 4 measurements. CONCLUSIONS: The developed phantom provides stable fluid flow useful for frequent clinical Doppler ultrasound testing and attempts to address several obstacles facing Doppler phantom testing. Such an ultrasound phantom can make routine testing more approachable for institutions that wish to initiate a Doppler QA program or complement a previously existing QA program. PMID- 27370159 TI - A new form of the calibration curve in radiochromic dosimetry. Properties and results. AB - PURPOSE: This work describes a new form of the calibration curve for radiochromic dosimetry that depends on one fit parameter. Some results are reported to show that the new curve performs as well as those previously used and, more importantly, significantly reduces the dependence on the lot of films, the film orientation on the scanner, and the time after exposure. METHODS: The form of the response curve makes use of the net optical densities ratio against the dose and has been studied by means of the Beer-Lambert law and a simple modeling of the film. The new calibration curve has been applied to EBT3 films exposed at 6 and 15 MV energy beams of linear accelerators and read-out in transmission mode by means of a flatbed color scanner. Its performance has been compared to that of two established forms of the calibration curve, which use the optical density and the net optical density against the dose. Four series of measurements with four lots of EBT3 films were used to evaluate the precision, accuracy, and dependence on the time after exposure, orientation on the scanner and lot of films. RESULTS: The new calibration curve is roughly subject to the same dose uncertainty, about 2% (1 standard deviation), and has the same accuracy, about 1.5% (dose values between 50 and 450 cGy), as the other calibration curves when films of the same lot are used. Moreover, the new calibration curve, albeit obtained from only one lot of film, shows a good agreement with experimental data from all other lots of EBT3 films used, with an accuracy of about 2% and a relative dose precision of 2.4% (1 standard deviation). The agreement also holds for changes of the film orientation and of the time after exposure. CONCLUSIONS: The dose accuracy of this new form of the calibration curve is always equal to or better than those obtained from the two types of curves previously used. The use of the net optical densities ratio considerably reduces the dependence on the lot of films, the landscape/portrait orientation, and the time after exposure. This form of the calibration curve could become even more useful with new optical digital devices using monochromatic light. PMID- 27370160 TI - Charged particle transport in magnetic fields in EGSnrc. AB - PURPOSE: To accurately and efficiently implement charged particle transport in a magnetic field in EGSnrc and validate the code for the use in phantom and ion chamber simulations. METHODS: The effect of the magnetic field on the particle motion and position is determined using one- and three-point numerical integrations of the Lorentz force on the charged particle and is added to the condensed history calculation performed by the EGSnrc PRESTA-II algorithm. The code is tested with a Fano test adapted for the presence of magnetic fields. The code is compatible with all EGSnrc based applications, including egs++. Ion chamber calculations are compared to experimental measurements and the effect of the code on the efficiency and timing is determined. RESULTS: Agreement with the Fano test's theoretical value is obtained at the 0.1% level for large step-sizes and in magnetic fields as strong as 5 T. The NE2571 dose calculations achieve agreement with the experiment within 0.5% up to 1 T beyond which deviations up to 1.2% are observed. Uniform air gaps of 0.5 and 1 mm and a misalignment of the incoming photon beam with the magnetic field are found to produce variations in the normalized dose on the order of 1%. These findings necessitate a clear definition of all experimental conditions to allow for accurate Monte Carlo simulations. It is found that ion chamber simulation times are increased by only 38%, and a 10 * 10 * 6 cm(3) water phantom with (3 mm)(3) voxels experiences a 48% increase in simulation time as compared to the default EGSnrc with no magnetic field. CONCLUSIONS: The incorporation of the effect of the magnetic fields in EGSnrc provides the capability to calculate high accuracy ion chamber and phantom doses for the use in MRI-radiation systems. Further, the effect of apparently insignificant experimental details is found to be accentuated by the presence of the magnetic field. PMID- 27370161 TI - Comment on "Medical use of all high activity sources should be eliminated for security concerns" [Med. Phys. 42, 6773-6775 (2015)]. PMID- 27370162 TI - Response to "Comment on 'Medical use of all high activity sources should be eliminated for security concerns' " [Med. Phys. 42, 6773-6775 (2015)]. PMID- 27370163 TI - Comment on "Medical physicist assistants are a bad idea" [Med. Phys. 43, 1-3 (2016)]. PMID- 27370164 TI - Response to "Comment on 'Medical physicist assistants are a bad idea' " [Med. Phys. 43, 1-3 (2016)]. PMID- 27370166 TI - Association between state school nutrition laws and subsequent child obesity. AB - Many states have enacted laws to improve school nutrition. We tested whether stronger state nutrition laws are associated with subsequently decreased obesity. We conducted a retrospective national multi-year panel data study (analyzed 2014 2016 at the Children's Hospital of Philadelphia). The predictors were 2010 laws regarding 9 nutrition categories from the Classification of Laws Associated with School Students, which grades the strength of state laws (none, weak, or strong). The outcome was weight status (healthy weight, overweight, or obese) in elementary, middle, and high school from the 2011/2012 National Survey of Children's Health. We tested the association between the strength of laws and weight using multinomial logistic regression. To further evaluate our main results, we conducted state-level longitudinal analyses testing the association between competitive food and beverage laws on the change in obesity from 2003 2011. In main analyses of 40,177 children ages 10-17years, we found strong state laws restricting the sale of competitive food and beverages in elementary school (OR: 0.68; 95% CI: 0.48, 0.96) and strong advertising laws across all grades (OR: 0.63; 95% CI: 0.46, 0.86) were associated with reduced odds of obesity. In longitudinal analyses, states with strong competitive food and beverage laws from 2003-2010 had small but significant decreases in obesity, compared to states with no laws. Although further research is needed to determine the causal effect of these laws, this study suggests that strong state laws limiting the sale and advertising of unhealthy foods and beverages in schools are associated with decreased obesity rates. PMID- 27370165 TI - Associations between physical activity and the neighbourhood social environment: baseline results from the HABITAT multilevel study. AB - Limitations have arisen when measuring associations between the neighbourhood social environment and physical activity, including same-source bias, and the reliability of aggregated neighbourhood-level social environment measures. This study examines cross-sectional associations between the neighbourhood social environment (perceptions of incivilities, crime, and social cohesion) and self reported physical activity, while accounting for same-source bias and reliability of neighbourhood-level exposure measures, using data from a large population based clustered sample. This investigation included 11,035 residents aged 40 65years from 200 neighbourhoods in Brisbane, Australia, in 2007. Respondents self reported their physical activity and perceptions of the social environment (neighbourhood incivilities, crime and safety, and social cohesion). Models were adjusted for individual-level education, occupation, and household income, and neighbourhood disadvantage. Exposure measures were generated via split clusters and an empirical Bayes estimation procedure. Data were analysed in 2016 using multilevel multinomial logistic regression. Residents of neighbourhoods with the highest incivilities and crime, and lowest social cohesion were reference categories. Individuals were more likely to be in the higher physical activity categories if they were in neighbourhoods with the lowest incivilities and the lowest crime. No associations were found between social cohesion and physical activity. This study provides a basis from which to gain a clearer understanding of the relationship between the neighbourhood social environment and individual physical activity. Further work is required to explore the pathways between perceptions of the neighbourhood social environment and physical activity. PMID- 27370167 TI - Risk of second primary cancer after a first potentially-human papillomavirus related cancer: A population-based study. AB - Human papillomaviruses (HPV) are involved in the development of anogenital and head and neck cancers. The purpose of this study was to assess the risk of developing a second primary cancer (SPC) after a first potentially-HPV-related cancer, and to analyze the sites where SPCs most frequently occurred in these patients. All patients with a first cancer diagnosed between 1989 and 2004, as recorded by 10 French cancer registries, were followed up until December 31, 2007. Only invasive potentially-HPV-related cancers (namely, cervical, vagina, vulva, anal canal, penile, oropharynx, tongue and tonsil) were included. Standardized Incidence Ratios (SIRs) were calculated to assess the risk of SPC. A multivariate Poisson regression model was used to model SIRs separately by gender, adjusted for the characteristics of the first cancer. 10,127 patients presented a first potentially-HPV-related cancer. The overall SIR was 2.48 (95% CI, 2.34-2.63). The SIR was 3.59 (95% CI, 3.33-3.86) and 1.61 (95% CI, 1.46-1.78) in men and women respectively. The relative risk of potentially-HPV-related SPC was high among these patients (SIR=13.74; 95% CI, 8.80-20.45 and 6.78; 95% CI, 4.61-9.63 for men and women, respectively). Women diagnosed in the most recent period (2000-2004) showed a 40% increase of their relative risk of SPC as compared with women diagnosed between 1989 and 1994 (ratio of SIRs=1.40; 95% CI, 1.06-1.85). HPV cancer survivors face an increased risk of SPC, especially second cancer. Clinicians may consider this increased risk of developing HPV-related SPC during follow-up to improve subsequent cancer prevention in these patients. PMID- 27370169 TI - The 90 90 90 strategy to end the HIV Pandemic by 2030: Can the supply chain handle it? AB - INTRODUCTION: UNAIDS "90-90-90" strategy calls for 90% of HIV-infected individuals to be diagnosed by 2020, 90% of whom will be on anti-retroviral therapy (ART) and 90% of whom will achieve sustained virologic suppression. Reaching these targets by 2020 will reduce the HIV epidemic to a low-level endemic disease by 2030. However, moving the global response towards this universal test and treat model will pose huge challenges to public health systems in resource-limited settings, including global and local supply chain systems. These challenges are especially acute in Africa, which accounts for over 70% of the persons affected by HIV. DISCUSSION: From a supply chain perspective, each of the "90's" has possible complications and roadblocks towards realizing the promise envisioned by 90-90-90. For instance, ensuring that 90% of HIV-infected persons know their status will require a large increase in access to HIV tests compared with what is currently available. To ensure that there are enough anti retrovirals available to treat the nearly 25 million people that will require them by 2020 represents a near doubling of the ARV supplied to treat the 13 million currently on treatment. Similarly, to monitor those on treatment means an unprecedented scale-up of viral load testing throughout Africa. CONCLUSIONS: Larger issues include whether the capacity exists at the local level to handle these commodities when they arrive in the most severely affected countries, including considerations of the human resources and costs needed to make this strategy effective. We believe that such "real world" analysis of proposed strategies and policies is essential to ensure their most effective implementation. PMID- 27370170 TI - Peri-implant femoral fractures: The risk is more than three times higher within PFN compared with DHS. AB - INTRODUCTION: Information is lacking regarding incidence rates, treatment regimens, and outcomes concerning peri-implant femoral fractures (PIF). Therefore, we performed a retrospective study to provide scientific data concerning incidence and outcome of PIF following osteosynthesis of proximal femoral fractures (PFF). MATERIAL AND METHODS: We retrospectively included all patients who received osteosynthesis for PFF between 2006 and 2015 and in whom PIF was confirmed postoperatively. All available patients with PIF were contacted minimum one year post-surgery. RESULTS: A total of 1314 osteosynthesis procedures were performed, of which 705 were proximal femoral nails (PFNs), 597 were dynamic hip screws (DHSs), and 12 were screws appliances only. During the same period, 18 PIFs (1.4%) were reported. However, PIF was 3.7 times higher within PFN when compared to DHS (15/705:2.1% versus 3/597:0.5%; odds ratio: 3.7). The following analysis also included 8 patients with PIF who were referred from other hospitals, resulting in a total of 26 patients. Mean patient age was 84.8 years (range, 57-95), with a predominance in female (23*) and in the left femur (19*). PIF occurred after an average of 23.6 months (range, 1-81) post-surgery. The fractures, most of which were spiral-shaped, were most commonly treated with locking plate osteosynthesis. The surgical revision rate was 7.7%, and the one year mortality was 23.1%. At an average of 43.0 months (range, 12-100) post surgery, it was possible to contact 18/26 patients (69.2%), and their mean Parker Mobility Score was 5.2 points (range 2-9). CONCLUSIONS: Peri-implant femoral fracture is a rare incident within the old age traumatology of PFF. However, based on our small number of cases, it occurred within PFN much more frequently compared with DHS. Locking plate osteosynthesis has been shown to be effective and reliable. Surgical revision and mortality rates do not appear to be increased when compared to those with the initial treatment of proximal femoral fractures. PMID- 27370171 TI - Is there any place for the variable angle proximal femoral plate? A case matched cohort study against the Dynamic Hip Screw system. AB - INTRODUCTION: The Variable angle Martin Plate (MP) is designed to offer patient specific adaption for the treatment of intertrochanteric hip fractures. Its proposed benefits include optimization of lag screw placement, plate shaft congruence and reduced risk of failure. Often its use has been criticized as representing a poor reduction of the fracture. The purpose of this study was to assess for a poorer quality of reduction, and compare functional outcomes and mortality, using a MP to that of a fixed angle Dynamic Hip Screw (DHS) in a matched cohort of patients. METHODS: A retrospective review of a prospective fracture database system was undertaken between 1st January 2004 to 31st December 2013. MP patients were matched to a cohort of DHS patients. Outcomes measure were a quality of procedure score(QPS), 1-year mortality rates, reoperation rates, and Barthel Index functional outcome. Minimum follow up was 12 months. RESULTS: A total of 77 Martin Plate patients were identified and case matched. The mean pre- and post-op Neck Shaft Angle (NSA) in the MPs was significantly different (132.97+/-7.78 Vs 126+/-8.62; p<0.0001). Conversely, the mean pre op DHS NSA and the mean post op NSA was not (p=0.397). Mean Tip-Apex Distance (TAD) was significantly different between groups; MP mean 26.51+/-9.09mm vs DHS 23.50+/ 8.14mm (p=0.023). The QPS consisted of 4 variables. A significant inverse relationship between QPS and the incidence of construct related complications exists. TAD>25mm, and a change in AP NSA of >5 degrees conveyed the greatest risk of complications. No difference occurred in complications, nor 12-month mortality. CONCLUSIONS: No statistical difference was found in the quality of reduction between MP and DHS in this group of matched patients. QPS demonstrated a significant inverse correlation with implant-related complications. No significant difference was noted in the incidence of complications, Barthel Index functional scores, or 12-month mortality between implants. A rationale exists regarding the use of MPs, particularly in patients with varus NSA. However, planning and adequate reduction are essential regardless of implant choice. PMID- 27370172 TI - Multisystemic Therapy((r)) : Clinical Overview, Outcomes, and Implementation Research. AB - Multisystemic therapy (MST) is an evidence-based treatment originally developed for youth with serious antisocial behavior who are at high risk for out-of-home placement and their families; and subsequently adapted to address other challenging clinical problems experience by youths and their families. The social ecological theoretical framework of MST is presented as well as its home-based model of treatment delivery, defining clinical intervention strategies, and ongoing quality assurance/quality improvement system. With more than 100 peer reviewed outcome and implementation journal articles published as of January 2016, the majority by independent investigators, MST is one of the most extensively evaluated family based treatments. Outcome research has yielded almost uniformly favorable results for youths and families, and implementation research has demonstrated the importance of treatment and program fidelity in achieving such outcomes. PMID- 27370173 TI - Endoscopic mucosal resection and endoscopic submucosal dissection for colorectal lesions: A systematic review. AB - AIM: To assess the efficacy and safety of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for the treatment of colorectal lesions. METHODS: A literature search was conducted from January 2000 to May 2015. The main outcomes were: recurrence after "en bloc" and "piecemeal" resection; procedure related adverse events; the EMR endoscopic success rate and the completely eradicated resection rate (R0) after ESD. RESULTS: A total of 66 studies were included in the analysis. The total number of lesions was 17950 (EMR: 11.873; ESD: 6077). Recurrence rate was higher in the EMR than ESD group (765/7303l vs. 50/3910 OR 8.19, 95% CI 6.2-10.9 p<0.0001). EMR-en bloc resection was achieved in 6793/10803 lesions (62.8%) while ESD-en bloc resection was obtained in 5500/6077 lesions (90.5%) (OR 0.18, p<0.0001, 95% CI 0.16-0.2). Perforation occurred more frequently in ESD than in EMR group (p<0.0001, OR 0.19, 95% CI 0.15-0.24). CONCLUSIONS: Endoscopic resection of large colorectal lesions is safe and effective. Compared with EMR, ESD results in higher "en bloc" resection rate and lower local recurrence rate, however ESD has high procedure related complication rates. PMID- 27370174 TI - Chronic lymphocytic leukaemia. AB - Chronic lymphocytic leukaemia (CLL) is the most common leukaemia among the adults in the Western World. CLL (and the corresponding nodal entity small lymphocytic lymphoma, SLL) is classified as a lymphoproliferative disorder characterised by the relentless accumulation of mature B-lymphocytes showing a peculiar immunophenotype in the peripheral blood, bone marrow, lymph nodes and spleen. CLL clinical course is very heterogeneous: the majority of patients follow an indolent clinical course with no or delayed treatment need and with a prolonged survival, while others experience aggressive disease requiring early treatment followed by frequent relapses. In the last decade, the improved understanding of CLL pathogenesis shed light on premalignant conditions (i.e., monoclonal B-cell lymphocytosis, MBL), defined new prognostic and predictive markers, improving patient stratification, but also broadened the therapeutic armamentarium with novel agents, targeting fundamental signaling pathways. PMID- 27370175 TI - Re: Magnetic Resonance Imaging-Ultrasound Fusion Targeted Prostate Biopsy in a Consecutive Cohort of Men with No Previous Biopsy: Reduction of Over Detection Through Improved Risk Stratification. PMID- 27370176 TI - Re: Update on Lasers in Urology. Current Assessment on Holmium:yttrium-aluminum garnet (Ho:YAG) Laser Lithotripter Settings and Laser Fibers. PMID- 27370177 TI - Bladder Cancer Incidence and Mortality: A Global Overview and Recent Trends. AB - CONTEXT: Bladder cancer has become a common cancer globally, with an estimated 430 000 new cases diagnosed in 2012. OBJECTIVE: We examine the most recent global bladder cancer incidence and mortality patterns and trends, the current understanding of the aetiology of the disease, and specific issues that may influence the registration and reporting of bladder cancer. EVIDENCE ACQUISITION: Global bladder cancer incidence and mortality statistics are based on data from the International Agency for Research on Cancer and the World Health Organisation (Cancer Incidence in Five Continents, GLOBOCAN, and the World Health Organisation Mortality). EVIDENCE SYNTHESIS: Bladder cancer ranks as the ninth most frequently diagnosed cancer worldwide, with the highest incidence rates observed in men in Southern and Western Europe, North America, as well in certain countries in Northern Africa or Western Asia. Incidence rates are consistently lower in women than men, although sex differences varied greatly between countries. Diverging incidence trends were also observed by sex in many countries, with stabilising or declining rates in men but some increasing trends seen for women. Bladder cancer ranks 13th in terms of deaths ranks, with mortality rates decreasing particularly in the most developed countries; the exceptions are countries undergoing rapid economic transition, including in Central and South America, some central, southern, and eastern European countries, and the Baltic countries. CONCLUSIONS: The observed patterns and trends of bladder cancer incidence worldwide appear to reflect the prevalence of tobacco smoking, although infection with Schistosoma haematobium and other risk factors are major causes in selected populations. Differences in coding and registration practices need to be considered when comparing bladder cancer statistics geographically or over time. PATIENT SUMMARY: The main risk factor for bladder cancer is tobacco smoking. The observed patterns and trends of bladder cancer incidence worldwide appear to reflect the prevalence of tobacco smoking. PMID- 27370178 TI - Challenges and perspectives in quantitative NMR. AB - This perspective article summarizes, from the author's point of view at the beginning of 2016, the major challenges and perspectives in the field of quantitative NMR. The key concepts in quantitative NMR are first summarized; then, the most recent evolutions in terms of resolution and sensitivity are discussed, as well as some potential future research directions in this field. A particular focus is made on methodologies capable of boosting the resolution and sensitivity of quantitative NMR, which could open application perspectives in fields where the sample complexity and the analyte concentrations are particularly challenging. These include multi-dimensional quantitative NMR and hyperpolarization techniques such as para-hydrogen-induced polarization or dynamic nuclear polarization. Because quantitative NMR cannot be dissociated from the key concepts of analytical chemistry, i.e. trueness and precision, the methodological developments are systematically described together with their level of analytical performance. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27370179 TI - A case based reflection on communicating end of life information in non-English speaking patients. AB - Mr X was a 56year old Chinese man (non-English speaking), who presented to the emergency department with a range of non-specific symptoms. On full workup, he was diagnosed with an advanced cancer of the pancreas. It was an aggressive, highly treatment resistant cancer, with an alarmingly poor prognosis. Before the diagnosis had been made, the family had informed our team that we were not to discuss medical issues with Mr X directly, and that upon arriving on a diagnosis we were to come to them first and they would subsequently inform him. They reported that Mr X was in support of this arrangement. Eventually we told the family about Mr X's diagnosis, and they asserted their collective will to keep this information from him, reaffirming that all medical discussion go through them. However, the doctor in charge explained the diagnosis to Mr X using an interpreter while his family were away from his bed. In this discussion, I consider this case from the perspective of respecting patients' and families' preferences around medical treatment and care. PMID- 27370180 TI - Screening for asymptomatic bacteriuria before total joint arthroplasty. PMID- 27370181 TI - Helicobacter pylori Peptidyl Prolyl Isomerase Expression Is Associated with the Severity of Gastritis. AB - PURPOSE: Helicobacter pylori secretory peptidyl prolyl isomerase, HP0175, is progressively identified as a pro-inflammatory and pro-carcinogenic protein, which serves to link H. pylori infection to its more severe clinical outcomes. Here, we have analyzed host HP0175-specific antibody responses in relation to the severity of gastritis. METHODS: The HP0175 gene fragment was PCR-amplified, cloned, expressed and purified by Ni-NTA affinity chromatography. Serum antigen specific antibody responses of non-ulcer dyspeptic patients (N = 176) against recombinant HP0175 were detected by western blotting. The infection status of these subjects was determined by rapid urease test, culture, histology, and serology. The grade of inflammation and stage of atrophy were scored blindly according to the OLGA staging system. RESULTS: The recombinant HP0175 (rHP0175) was expressed as a ~35 kDa protein and its identity was confirmed by western blotting using anti-6X His tag antibody and pooled H. pylori-positive sera. Serum IgG antibodies against rHP0175 segregated our patients into two similar-sized groups of sero-positives (90/176, 51.1 %) and sero-negatives (86/176, 48.9 %). The former presented with higher grades of gastric inflammation (OR = 4.4, 95 % CI = 1.9-9.9, P = 0.001) and stages of gastric atrophy (OR = 18.3, 95 %CI = 1.4 246.6, P = 0.028). CONCLUSION: Our findings lend further support to the pro inflammatory nature of H. pylori peptidyl prolyl isomerase (HP0175) and recommends this antigen as a non-invasive serum biomarker of the severity of H. pylori-associated gastritis. PMID- 27370183 TI - Distribution of common stickleback parasites on North Uist, Scotland, in relation to ecology and host traits. AB - Analysing spatial differences among macroparasite communities is an important tool in the study of host-parasite interactions. Identifying patterns can shed light on the underlying causes of heterogeneity of parasite distribution and help to better understand ecological constraints and the relative importance of host and parasite adaptations. In the present study, we aimed to find correlational evidence that the macroparasite distribution patterns on the Scottish island of North Uist, which had been described by de Roij and MacColl (2012), are indicative of local processes rather than an unspecific influence of habitat characteristics. We therefore reinvestigated parasite abundances and tested for associations with habitat characteristics and host traits. Distribution patterns of the most common parasites were largely consistent with the observations of de Roij and MacColl (2012). In accordance with the published results, we found that the most obvious abiotic habitat characteristic varying among the lakes on the island, pH, did not statistically explain parasite abundances (except for eye fluke species inside the lens). Instead, we found that genetic differentiation between host populations, measured as pairwise FST values based on available microsatellite data, was significantly correlated with dissimilarity in parasite community composition. Our results indicate that individual lake characteristics rather than physicochemical variables shape parasite distribution on this island, making it an ideal place to study host-parasite interactions. Furthermore, additionally to geographic distance measures taken from maps, we suggest taking into account connectivity among freshwater habitats, indirectly measured via fish population structure, to analyse spatial distribution patterns. PMID- 27370185 TI - [Not Available]. PMID- 27370184 TI - Novel Intracorporeal Esophagojejunostomy Using Linear Staplers During Laparoscopic Total Gastrectomy: pi-Shaped Esophagojejunostomy, 3-in-1 Technique. PMID- 27370186 TI - [Not Available]. PMID- 27370188 TI - [Not Available]. PMID- 27370187 TI - [Not Available]. PMID- 27370189 TI - [Not Available]. PMID- 27370190 TI - [Not Available]. PMID- 27370192 TI - [Not Available]. PMID- 27370191 TI - [Not Available]. PMID- 27370193 TI - [Not Available]. PMID- 27370194 TI - [Not Available]. PMID- 27370195 TI - [Not Available]. PMID- 27370196 TI - [Not Available]. PMID- 27370197 TI - [Not Available]. PMID- 27370198 TI - [Not Available]. PMID- 27370199 TI - [Not Available]. PMID- 27370200 TI - [Not Available]. PMID- 27370201 TI - [Not Available]. PMID- 27370202 TI - [Not Available]. PMID- 27370203 TI - Contrast enhancement of carotid adventitial vasa vasorum as a biomarker of radiation-induced atherosclerosis. AB - PURPOSE: Abnormal proliferation of adventitial vasa vasorum (vv) occurs early at sites of atherosclerosis and is thought to be an early biomarker of vascular damage. Contrast-enhanced ultrasound (CEUS) can detect this process. Its usefulness in irradiated arteries as a measure of accelerated atherosclerosis is unknown. This study investigates contrast intensity in carotid adventitia as an early marker of radiation-induced damage in head and neck cancer (HNC) patients. MATERIALS/METHODS: Patients with HNC treated with a wedged-pair and matched neck technique or hemi-neck radiotherapy (RT) (unirradiated side as control) at least 2years previously were included. Patients had been prescribed a dose of at least 50Gy to the neck. CEUS was performed on both carotid arteries and a region of interest was selected in the adventitia of the far wall of both left and right distal common carotid arteries. Novel quantification software was used to compare the average intensity per pixel between irradiated and unirradiated arteries. RESULTS: 48 patients (34 males) with median age of 59.2years (interquartile range (IQR) 49.2-64.2) were included. The mean maximum point dose to the irradiated artery was 61.2Gy (IQR 52.6-61.8) and 1.1Gy (IQR 1.0-1.8Gy) to the unirradiated side. The median interval from RT was 59.4months (IQR 41-88.7). There was a significant difference in the mean (SD) contrast intensity per pixel on the irradiated side (1.1 (0.4)) versus 0.96 (0.34) on the unirradiated side (p=0.01). After attenuation correction, the difference in mean contrast intensity per pixel was still significant (1.4 (0.58) versus 1.2 (0.47) (p=0.02). Previous surgery or chemotherapy had no effect on the difference in contrast intensity between the 2 sides of the neck. Mean intensity per pixel did not correlate to traditional risk prediction models (carotid intima-medial thickness, QSTROKE score). CONCLUSIONS: Proliferation of vv is demonstrated by increased contrast intensity in irradiated carotid arteries. This may be a useful, independent biomarker of radiation induced carotid atherosclerosis when used as a tool to quantify neovascularization. PMID- 27370204 TI - Independent external validation of predictive models for urinary dysfunction following external beam radiotherapy of the prostate: Issues in model development and reporting. AB - BACKGROUND AND PURPOSE: Most predictive models are not sufficiently validated for prospective use. We performed independent external validation of published predictive models for urinary dysfunctions following radiotherapy of the prostate. MATERIALS/METHODS: Multivariable models developed to predict atomised and generalised urinary symptoms, both acute and late, were considered for validation using a dataset representing 754 participants from the TROG 03.04 RADAR trial. Endpoints and features were harmonised to match the predictive models. The overall performance, calibration and discrimination were assessed. RESULTS: 14 models from four publications were validated. The discrimination of the predictive models in an independent external validation cohort, measured using the area under the receiver operating characteristic (ROC) curve, ranged from 0.473 to 0.695, generally lower than in internal validation. 4 models had ROC >0.6. Shrinkage was required for all predictive models' coefficients ranging from -0.309 (prediction probability was inverse to observed proportion) to 0.823. Predictive models which include baseline symptoms as a feature produced the highest discrimination. Two models produced a predicted probability of 0 and 1 for all patients. CONCLUSIONS: Predictive models vary in performance and transferability illustrating the need for improvements in model development and reporting. Several models showed reasonable potential but efforts should be increased to improve performance. Baseline symptoms should always be considered as potential features for predictive models. PMID- 27370205 TI - Modelling second malignancy risks from low dose rate and high dose rate brachytherapy as monotherapy for localised prostate cancer. AB - BACKGROUND AND PURPOSE: To estimate the risks of radiation-induced rectal and bladder cancers following low dose rate (LDR) and high dose rate (HDR) brachytherapy as monotherapy for localised prostate cancer and compare to external beam radiotherapy techniques. MATERIALS AND METHODS: LDR and HDR brachytherapy monotherapy plans were generated for three prostate CT datasets. Second cancer risks were assessed using Schneider's concept of organ equivalent dose. LDR risks were assessed according to a mechanistic model and a bell-shaped model. HDR risks were assessed according to a bell-shaped model. Relative risks and excess absolute risks were estimated and compared to external beam techniques. RESULTS: Excess absolute risks of second rectal or bladder cancer were low for both LDR (irrespective of the model used for calculation) and HDR techniques. Average excess absolute risks of rectal cancer for LDR brachytherapy according to the mechanistic model were 0.71 per 10,000 person-years (PY) and 0.84 per 10,000 PY respectively, and according to the bell-shaped model, were 0.47 and 0.78 per 10,000 PY respectively. For HDR, the average excess absolute risks for second rectal and bladder cancers were 0.74 and 1.62 per 10,000 PY respectively. The absolute differences between techniques were very low and clinically irrelevant. Compared to external beam prostate radiotherapy techniques, LDR and HDR brachytherapy resulted in the lowest risks of second rectal and bladder cancer. CONCLUSIONS: This study shows both LDR and HDR brachytherapy monotherapy result in low estimated risks of radiation-induced rectal and bladder cancer. LDR resulted in lower bladder cancer risks than HDR, and lower or similar risks of rectal cancer. In absolute terms these differences between techniques were very small. Compared to external beam techniques, second rectal and bladder cancer risks were lowest for brachytherapy. PMID- 27370206 TI - Idiopathic intracranial hypertension eliminated by counterclockwise maxillomandibular advancement: a case report. AB - INTRODUCTION: Obstructive sleep apnea (OSA) is a secondary cause of intracranial hypertension (IH). Decreased jugular venous drainage has been seen in patients with idiopathic IH. CLINICAL PRESENTATION: A complex case of a 48-year-old female whose idiopathic IH was put into remission after counterclockwise maxillomandibular advancement (CC-MMA), despite persistence of her OSA. CONCLUSION: This case highlights the relationship between OSA and IH and points to the significant morbidity that can result from mild OSA and from what are considered borderline intracranial pressures. This indicates the need for a high index of suspicion for actual underlying pathology that can be surgically corrected when patients manifest symptoms of a somatic syndrome. This is the first report in the medical literature of clinical elimination of IH by CC-MMA. The authors propose that this positive outcome was effected via mandibular advancement producing a decrease in jugular venous resistance, allowing improved absorption of cerebrospinal fluid. PMID- 27370207 TI - DADM: The first 2 years of the Alzheimer Association's open access journal to support the research and development of novel biomarkers and diagnostic approaches. PMID- 27370208 TI - Recruitment of TBK1 to cytosol-invading Salmonella induces WIPI2-dependent antibacterial autophagy. AB - Mammalian cells deploy autophagy to defend their cytosol against bacterial invaders. Anti-bacterial autophagy relies on the core autophagy machinery, cargo receptors, and "eat-me" signals such as galectin-8 and ubiquitin that label bacteria as autophagy cargo. Anti-bacterial autophagy also requires the kinase TBK1, whose role in autophagy has remained enigmatic. Here we show that recruitment of WIPI2, itself essential for anti-bacterial autophagy, is dependent on the localization of catalytically active TBK1 to the vicinity of cytosolic bacteria. Experimental manipulation of TBK1 recruitment revealed that engagement of TBK1 with any of a variety of Salmonella-associated "eat-me" signals, including host-derived glycans and K48- and K63-linked ubiquitin chains, suffices to restrict bacterial proliferation. Promiscuity in recruiting TBK1 via independent signals may buffer TBK1 functionality from potential bacterial antagonism and thus be of evolutionary advantage to the host. PMID- 27370209 TI - Probing gamma-secretase-substrate interactions at the single amino acid residue level. PMID- 27370210 TI - Rapid rule out of acute myocardial infarction: novel biomarker-based strategies. PMID- 27370212 TI - Roles of vacuolar H+-ATPase in the oxidative stress response of Candida glabrata. AB - Vacuolar H(+)-ATPase (V-ATPase) is responsible for the acidification of eukaryotic intracellular compartments and plays an important role in oxidative stress response (OSR), but its molecular bases are largely unknown. Here, we investigated how V-ATPase is involved in the OSR by using a strain lacking VPH2, which encodes an assembly factor of V-ATPase, in the pathogenic fungus Candida glabrata The loss of Vph2 resulted in increased H2O2 sensitivity and intracellular reactive oxygen species (ROS) level independently of mitochondrial functions. The Deltavph2 mutant also displayed growth defects under alkaline conditions accompanied by the accumulation of intracellular ROS and these phenotypes were recovered in the presence of the ROS scavenger N-acetyl-l cysteine. Both expression and activity levels of mitochondrial manganese superoxide dismutase (Sod2) and catalase (Cta1) were decreased in the Deltavph2 mutant. Phenotypic analyses of strains lacking and overexpressing these genes revealed that Sod2 and Cta1 play a predominant role in endogenous and exogenous OSR, respectively. Furthermore, supplementation of copper and iron restored the expression of SOD2 specifically in the Deltavph2 mutant, suggesting that the homeostasis of intracellular cupper and iron levels maintained by V-ATPase was important for the Sod2-mediated OSR. This report demonstrates novel roles of V ATPase in the OSR in C. glabrata. PMID- 27370213 TI - [Not Available]. PMID- 27370211 TI - Faecal haemoglobin concentration is related to detection of advanced colorectal neoplasia in the next screening round. AB - Objective To examine associations between faecal haemoglobin concentrations below the cut-off used in colorectal cancer screening and outcomes in the next screening round. Methods In the Scottish Bowel Screening Programme, faecal haemoglobin concentrations and diagnostic outcomes were investigated for participants with a negative result (faecal haemoglobin concentrations < 80.0 ug Hb/g faeces), followed by a positive result within two years. Results Of 37,780 participants with negative results, at the next screening round, 556 (1.5%) screened positive and 30,293 (80.2%) negative. Initial median faecal haemoglobin concentrations (2.1 ug Hb/g faeces, IQR: 0.0-13.2) were higher in those with subsequent positive results than those with subsequent negative results (0.0 ug Hb/g faeces, IQR: 0.0-1.4; p < 0.0001). Using faecal haemoglobin concentrations 0.0-19.9 ug Hb/g faeces as reference, logistic regression analysis showed high adjusted odds ratios for advanced neoplasia (advanced neoplasia: colorectal cancer or higher risk adenoma) detection at the next round of 14.3 (95% CI: 8.9 23.1) in those with initial faecal haemoglobin concentrations 20.0-39.9 ug Hb/g faeces, and 38.0 (95% CI: 20.2-71.2) with 60.0-79.9 ug Hb/g faeces. Conclusions A higher proportion of participants with faecal haemoglobin concentrations of >= 20 ug Hb/g faeces had advanced neoplasia detected at the next round than participants with lower faecal haemoglobin concentrations. Although most relevant when using high faecal haemoglobin concentrations cut-offs, studies of faecal haemoglobin concentrations and outcomes over screening rounds may provide strategies to direct available colonoscopy towards those at highest risk. PMID- 27370214 TI - [Not Available]. PMID- 27370215 TI - [Not Available]. PMID- 27370216 TI - [Not Available]. PMID- 27370217 TI - [Not Available]. PMID- 27370218 TI - [Not Available]. PMID- 27370219 TI - [Not Available]. PMID- 27370220 TI - [Not Available]. PMID- 27370221 TI - [Not Available]. PMID- 27370222 TI - [Not Available]. PMID- 27370223 TI - [Not Available]. PMID- 27370224 TI - [Not Available]. PMID- 27370226 TI - TDP-43 regulates endogenous retrovirus-K viral protein accumulation. AB - The concomitant expression of neuronal TAR DNA binding protein 43 (TDP-43) and human endogenous retrovirus-K (ERVK) is a hallmark of ALS. Since the involvement of TDP-43 in retrovirus replication remains controversial, we sought to evaluate whether TDP-43 exerts an effect on ERVK expression. In this study, TDP-43 bound the ERVK promoter in the context of inflammation or proteasome inhibition, with no effect on ERVK transcription. However, over-expression of ALS-associated aggregating forms of TDP-43, but not wild-type TDP-43, significantly enhanced ERVK viral protein accumulation. Human astrocytes and neurons further demonstrated cell-type specific differences in their ability to express and clear ERVK proteins during inflammation and proteasome inhibition. Astrocytes, but not neurons, were able to clear excess ERVK proteins through stress granule formation and autophagy. In vitro findings were validated in autopsy motor cortex tissue from patients with ALS and neuro-normal controls. We further confirmed marked enhancement of ERVK in cortical neurons of patients with ALS. Despite evidence of enhanced stress granule and autophagic response in ALS cortical neurons, these cells failed to clear excess ERVK protein accumulation. This highlights how multiple cellular pathways, in conjunction with disease-associated mutations, can converge to modulate the expression and clearance of viral gene products from genomic elements such as ERVK. In ALS, ERVK protein aggregation is a novel aspect of TDP-43 misregulation contributing towards the pathology of this neurodegenerative disease. PMID- 27370225 TI - FGFR3 gene mutation plus GRB10 gene duplication in a patient with achondroplasia plus growth delay with prenatal onset. AB - BACKGROUND: Achondroplasia is a well-defined and common bone dysplasia. Genotype- and phenotype-level correlations have been found between the clinical symptoms of achondroplasia and achondroplasia-specific FGFR3 mutations. RESULT: A 2-year-old boy with clinical features consistent with achondroplasia and Silver-Russell syndrome-like symptoms was found to carry a mutation in the fibroblast growth factor receptor-3 (FGFR3) gene at c.1138G > A (p.Gly380Arg) and a de novo 574 kb duplication at chromosome 7p12.1 that involved the entire growth-factor receptor bound protein 10 (GRB10) gene. Using quantitative real-time PCR analysis, GRB10 was over-expressed, and, using enzyme-linked immunosorbent assays for IGF1 and IGF-binding protein-3 (IGFBP3), we found that IGF1 and IGFBP3 were low-expressed in this patient. CONCLUSIONS: We demonstrate that a combination of uncommon, rare and exceptional molecular defects related to the molecular bases of particular birth defects can be analyzed and diagnosed to potentially explain the observed variability in the combination of molecular defects. PMID- 27370227 TI - Co-transplantation of MRF-overexpressing oligodendrocyte precursor cells and Schwann cells promotes recovery in rat after spinal cord injury. AB - Oligodendrocyte (OL) replacement is a promising treatment strategy for spinal cord injury (SCI). However, the poor survival of transplanted OLs or their precursors and inhibition of axonal regeneration are two major challenges with this approach. Our previous study showed that Schwann cells (SCs) promoted survival, proliferation, and migration of transplanted OL progenitor cells (OPCs) and neurological recovery. Remyelination is an important basis for functional recovery following spinal cord injury. It has been reported that myelin gene regulatory factor (MRF), a transcriptional regulator which specifically is expressed in postmitotic OLs within the CNS, is essential for OL maturation and CNS myelination. In the present study, we investigated whether co-transplantation of MRF-overexpressing OPCs (MRF-OPCs) and SCs could improve functional recovery in a rat model of contusional SCI. MRF overexpression had no effect on OPC survival or migration, but stimulated the differentiation of OPCs both in vitro and in vivo. Co-transplantation of MRF-OPCs and SCs increased myelination and tissue repair after SCI, leading to the recovery of neurological function. These results indicate that co-transplantation of MRF-OPCs and SCs may be an effective treatment strategy for SCI. PMID- 27370228 TI - Zinc transporter 3 (ZnT3) gene deletion reduces spinal cord white matter damage and motor deficits in a murine MOG-induced multiple sclerosis model. AB - The present study aimed to evaluate the role of zinc transporter 3 (ZnT3) on multiple sclerosis (MS) pathogenesis. Experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis, was induced by immunization with myelin oligodendrocyte glycoprotein (MOG35-55) in female mice. Three weeks after the initial immunization, demyelination, immune cell infiltration and blood brain barrier (BBB) disruption in the spinal cord were analyzed. Clinical signs of EAE first appeared on day 11 and reached a peak level on day 19 after the initial immunization. ZnT3 gene deletion profoundly reduced the daily clinical score of EAE. The ZnT3 gene deletion-mediated inhibition of the clinical course of EAE was accompanied by suppression of inflammation and demyelination in the spinal cord. The motor deficit accompanying neuropathological changes associated with EAE were mild in ZnT3 gene deletion mice. This reduction in motor deficit was accompanied by coincident reductions in demyelination and infiltration of encephalitogenic immune cells including CD4+ T cells, CD8+ T cells, CD20+ B cells and F4/80+ microglia in the spinal cord. These results demonstrate that ZnT3 gene deletion inhibits the clinical features and neuropathological changes associated with EAE. ZnT3 gene deletion also remarkably inhibited formation of EAE-associated aberrant synaptic zinc patches, matrix metalloproteinases-9 (MMP-9) activation and BBB disruption. Therefore, amelioration of EAE-induced clinical and neuropathological changes by ZnT3 gene deletion suggests that vesicular zinc may be involved in several steps of MS pathogenesis. PMID- 27370229 TI - Rationale and study protocol for the 'eCoFit' randomized controlled trial: Integrating smartphone technology, social support and the outdoor physical environment to improve health-related fitness among adults at risk of, or diagnosed with, Type 2 Diabetes. AB - INTRODUCTION: The prevalence and risk of Type 2 Diabetes (T2D) has dramatically increased over the past decade. Physical activity (PA) has significant benefits for the treatment and prevention of T2D. The aim of this study is to develop, implement and evaluate a community-based PA intervention to improve aerobic and muscular fitness among adults at risk of, or diagnosed with T2D. RESEARCH DESIGN AND METHODS: The eCoFit pilot intervention will be evaluated using a randomized controlled trial (RCT) design. The 20-week (Phases 1 and 2) multi-component intervention was guided by Social Cognitive Theory, Health Action Process Approach Model, and Cognitive Behavior Therapy strategies. Phase 1 (Weeks 1-10) includes: i) 5 group face-to-face sessions consisting of outdoor training and cognitive mentoring; and ii) the use of the eCoFit smartphone application with a description of where and how to use the outdoor environment to be more physically active. Phase 2 (Weeks 11-20) includes the use of the eCoFit smartphone application only. Assessments are to be conducted at baseline, 10-weeks (primary end-point) and 20-weeks (secondary end-point) post-baseline. Primary outcomes are cardio-respiratory fitness and muscular fitness (lower body). Secondary outcomes include physical, behavioral, mental health and quality of life, and social cognitive outcomes. DISCUSSION: eCoFit is an innovative, multi-component intervention, which integrates smartphone technology, social support and the outdoor physical environment to promote aerobic and resistance training PA among adults at risk of, or diagnosed with T2D. The findings will be used to guide future interventions and to develop and implement effective community-based prevention programs. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry No: ACTRN12615000990527. PMID- 27370231 TI - Randomized controlled trial of a 12-month computerized mindfulness-based intervention for obese patients with binge eating disorder: The MindOb study protocol. AB - BACKGROUND: Mindfulness-based interventions for healthy behaviors such as exercise and dietary modifications have aroused growing interest. This study aims to test the effectiveness of a mindfulness-based intervention for the reduction of impulsive eating and the improvement of motivation to exercise among obese individuals. METHODS: One-hundred and twenty obese outpatients, aged 18 to 65years, diagnosed with a binge eating disorder, will be randomly assigned to one of the three following groups: mindfulness practice, sham meditation, or treatment as usual control. The tested intervention consists of a 1-year computerized mindfulness-based program. Mindfulness sessions are audio recordings that the patients are asked to listen to, 10min every day. Self-reported questionnaires measuring impulsive eating, motivation to exercise, physical activity level, mood, and mindfulness skills are filled in at baseline, 1, 6, and 12months. Physical activity, calories consumption, and biomarkers are measured with more objective measurement tools at baseline, 6months and 12months. CONCLUSION: Mindfulness, as both a de-automation element and as a moderator of motivation to exercise, can lead to the reduction of impulsive eating and also to an increase in levels of physical activity. These effects could cause weight loss in obese patients suffering from binge eating disorder. TRIAL REGISTRATION: clinicaltrials.gov: NCT02571387. PMID- 27370232 TI - [Not Available]. PMID- 27370230 TI - Can atorvastatin with metformin change the natural history of prostate cancer as characterized by molecular, metabolomic, imaging and pathological variables? A randomized controlled trial protocol. AB - BACKGROUND: Atorvastatin and metformin are known energy restricting mimetic agents that act synergistically to produce molecular and metabolic changes in advanced prostate cancer (PCa). This trial seeks to determine whether these drugs favourably alter selected parameters in men with clinically-localized, aggressive PCa. METHODS/DESIGN: This prospective phase II randomized, controlled window trial is recruiting men with clinically significant PCa, confirmed by biopsy following multiparametric MRI and intending to undergo radical prostatectomy. Ethical approval was granted by the Royal Brisbane and Women's Hospital Human and The University of Queensland Medical Research Ethics Committees. Participants are being randomized into four groups: metformin with placebo; atorvastatin with placebo; metformin with atorvastatin; or placebo alone. Capsules are consumed for 8weeks, a duration selected as the most appropriate period in which histological and biochemical changes may be observed while allowing prompt treatment with curative intent of clinically significant PCa. At recruitment and prior to RP, participants provide blood, urine and seminal fluid. A subset of participants will undergo 7Tesla magnetic resonance spectroscopy to compare metabolites in vivo with those in seminal fluid and biopsied tissue. The primary end point is biochemical evolution, defined using biomarkers (serum prostate specific antigen; PCA3 and citrate in seminal fluid and prostatic tissue). Standard pathological assessment will be undertaken. DISCUSSION: This study is designed to assess the potential synergistic action of metformin and atorvastatin on PCa tumour biology. The results may determine simple methods of tumour modulation to reduce disease progression. PMID- 27370233 TI - [Not Available]. PMID- 27370234 TI - [Not Available]. PMID- 27370235 TI - [Not Available]. PMID- 27370236 TI - [Not Available]. PMID- 27370237 TI - [Not Available]. PMID- 27370238 TI - [Not Available]. PMID- 27370239 TI - [Not Available]. PMID- 27370240 TI - [Not Available]. PMID- 27370241 TI - [Not Available]. PMID- 27370242 TI - [Not Available]. PMID- 27370243 TI - [Not Available]. PMID- 27370244 TI - [Not Available]. PMID- 27370245 TI - [Not Available]. PMID- 27370246 TI - [Not Available]. PMID- 27370247 TI - [Not Available]. PMID- 27370249 TI - [Not Available]. PMID- 27370250 TI - [Not Available]. PMID- 27370252 TI - [Not Available]. PMID- 27370251 TI - [Not Available]. PMID- 27370253 TI - [Not Available]. PMID- 27370254 TI - [Not Available]. PMID- 27370248 TI - Peptide-drug conjugates as effective prodrug strategies for targeted delivery. AB - Peptide-drug conjugates (PDCs) represent an important class of therapeutic agents that combine one or more drug molecules with a short peptide through a biodegradable linker. This prodrug strategy uniquely and specifically exploits the biological activities and self-assembling potential of small-molecule peptides to improve the treatment efficacy of medicinal compounds. We review here the recent progress in the design and synthesis of peptide-drug conjugates in the context of targeted drug delivery and cancer chemotherapy. We analyze carefully the key design features in choosing the peptide sequence and linker chemistry for the drug of interest, as well as the strategies to optimize the conjugate design. We highlight the recent progress in the design and synthesis of self-assembling peptide-drug amphiphiles to construct supramolecular nanomedicine and nanofiber hydrogels for both systemic and topical delivery of active pharmaceutical ingredients. PMID- 27370256 TI - [Not Available]. PMID- 27370257 TI - [Not Available]. PMID- 27370255 TI - Melatonin Protects SH-SY5Y Neuronal Cells Against Methamphetamine-Induced Endoplasmic Reticulum Stress and Apoptotic Cell Death. AB - Methamphetamine (METH), a psychostimulant with highly neurotoxic effects, has been known to induce neuronal apoptosis in part through an endoplasmic reticulum (ER) stress pathway. Melatonin is an endogenous antioxidant compound that exerts protective effects against several neurodegenerative conditions, including METH induced neurotoxicity, via various mechanisms. However, the role of melatonin in ER stress is still relatively unclear. In the present study, we investigated ER stress and neuronal apoptosis following METH treatment and the role of melatonin in METH-mediated ER stress-induced cell death in the SH-SY5Y neuroblastoma cell line. We found that METH caused the overexpression of ER stress-related genes, including C/EBP homologous protein and spliced X-box binding protein 1, in dose- and time-dependent manners. Moreover, METH time-dependently activated caspase-12 and -3, leading to cellular apoptosis. Furthermore, we demonstrated that pretreatment with melatonin attenuated the overexpression of ER stress-related genes and the cleavages of caspase-12 and -3 caused by METH exposure. Flow cytometry revealed that METH-mediated neuronal apoptosis was also prevented by melatonin. These findings suggest the protective effects of melatonin against ER stress and apoptosis caused by METH and other harmful agents. PMID- 27370258 TI - [Not Available]. PMID- 27370260 TI - [Not Available]. PMID- 27370259 TI - [Not Available]. PMID- 27370261 TI - [Not Available]. PMID- 27370262 TI - [Not Available]. PMID- 27370263 TI - [Not Available]. PMID- 27370265 TI - [Not Available]. PMID- 27370264 TI - [Not Available]. PMID- 27370266 TI - Erratum to: Association of Bisphenol A Exposure with Breastfeeding and Perceived Insufficient Milk Supply in Mexican Women. PMID- 27370267 TI - [Technique-based game for daycare visitors with and without dementia : Effects, heuristics and correlates]. AB - BACKGROUND: Playing of old people with or without dementia have not yet been substantially investigated. OBJECTIVE: This study deals with the acceptance and impact of a tablet-based memory game, which was played on a weekly or semiweekly basis by visitors in two daycare units. MATERIAL AND METHODS: Within the framework of focus groups the technical system was adapted for elderly users. The video-assisted data at the level of the game and the dynamics were investigated with respect to interaction and communication. RESULTS: The analysis of psychological observation forms and game protocols, which were conducted over a period of 3 months, indicated different effects of the game on psychosocial and cognitive activation. The individual memory cards in particular served as an intensification of communication and a stimulation of episodic memory. Finally, with video analysis during the whole game setting three theoretical relationship patterns of the spheres playing and speech could be depicted. CONCLUSION: Coherence, separation and incoherence of playing and speech are different forms of interaction in which individual and collaborative competences of people with and without dementia can be visualized. Furthermore, the study provides evidence for the cultural theory of playing by Huizinga. PMID- 27370268 TI - Diagnosis and management of asthma - Statement on the 2015 GINA Guidelines. AB - This statement was written by a group of pulmonologists and pediatric pulmonologists belonging to the corresponding professional associations OGP (Austrian Society for Pulmonology) and OGKJ (Austrian Society for pediatric and adolescent medicine) to provide a concise overview of the latest updates in the 2015 GINA Guidelines and to include aspects that are specific to Austria. PMID- 27370269 TI - Uterine rupture after balloon inflation of the intrauterine Foley catheter during laparoscopic chromopertubation. AB - Laparoscopic chromopertubation is considered "gold standard" for checking the tubal patency. Foley catheter is frequently used for blue dye during chromopertubation. Complications associated with the intra-uterine use of Foley catheter are infrequent. The mean normal capacity of the uterine cavity is about 9 ml, and an inflation of up to 30 ml (e. g. during thermal balloon ablation procedures) is considered safe. We report a uterine rupture in a 36-year-old woman undergoing laparoscopic chromopertubation due to primary infertility. Thirteen years ago, the patient had three consecutive laparotomies because of appendicitis, peritonitis and retroperitoneal abscess. For the present laparoscopy, the Foley catheter (Nelaton, charier 10, balloon 5 ml) was used. The first blocking of the balloon with 3.5 ml saline was insufficient; however after inflating with 5 ml, a rupture of the uterine fundus occurred. The balloon remained intact and both tubes appeared patent. The myometrium was sutured and the postoperative course was uneventful. We presume that-in the present case-the expansive capacity of the uterine wall may have been reduced after the series of severe pelvic inflammations. Nevertheless, if using a Foley catheter for the chromopertubation, the optimal pressure for its intrauterine fixation needs still to be determined. PMID- 27370272 TI - [Not Available]. PMID- 27370273 TI - [Not Available]. PMID- 27370270 TI - miR-122-mediated translational repression of PEG10 and its suppression in human hepatocellular carcinoma. AB - BACKGROUND: Hepatocellular carcinoma (HCC), a primary liver malignancy, is the most common cancer in males and fourth common cancer in females in Taiwan. HCC patients usually have a poor prognosis due to late diagnosis. It has been classified as a complex disease because of the heterogeneous phenotypic and genetic traits of the patients and a wide range of risk factors. Micro (mi)RNAs regulate oncogenes and tumor suppressor genes that are known to be dysregulated in HCC. Several studies have found an association between downregulation of miR 122, a liver-specific miRNA, and upregulation of paternally expressed gene 10 (PEG10) in HCC; however, the correlation between low miR-122 and high PEG10 levels still remains to be defined and require more investigations to evaluate their performance as an effective prognostic biomarker for HCC. METHODS: An in silico approach was used to isolate PEG10, a potential miR-122 target implicated in HCC development. miR-122S binding sites in the PEG10 promoter were evaluated with a reporter assay. The regulation of PEG10 by miR-122S overexpression was examined by quantitative RT-PCR, western blotting, and immunohistochemistry in miR-122 knockout mice and liver tissue from HCC patients. The relationship between PEG10 expression and clinicopathologic features of HCC patients was also evaluated. RESULTS: miR-122 downregulated the expression of PEG10 protein through binding to 3'-untranslated region (UTR) of the PEG10 transcript. In miR-122 knockout mice and HCC patients, the deficiency of miR-122 was associated with HCC progression. The expression of PEG10 was increased in 57.3 % of HCC as compared to paired non-cancerous tissue samples. However, significant upregulation was detected in 56.5 % of patients and was correlated with Okuda stage (P = 0.05) and histological grade (P = 0.001). CONCLUSIONS: miR-122 suppresses PEG10 expression via direct binding to the 3'-UTR of the PEG10 transcript. Therefore, while PEG10 could not be an ideal diagnostic biomarker for HCC but its upregulation in HCC tissue still has predictive value for HCC prognosis. PMID- 27370271 TI - Normalizing acronyms and abbreviations to aid patient understanding of clinical texts: ShARe/CLEF eHealth Challenge 2013, Task 2. AB - BACKGROUND: The ShARe/CLEF eHealth challenge lab aims to stimulate development of natural language processing and information retrieval technologies to aid patients in understanding their clinical reports. In clinical text, acronyms and abbreviations, also referenced as short forms, can be difficult for patients to understand. For one of three shared tasks in 2013 (Task 2), we generated a reference standard of clinical short forms normalized to the Unified Medical Language System. This reference standard can be used to improve patient understanding by linking to web sources with lay descriptions of annotated short forms or by substituting short forms with a more simplified, lay term. METHODS: In this study, we evaluate 1) accuracy of participating systems' normalizing short forms compared to a majority sense baseline approach, 2) performance of participants' systems for short forms with variable majority sense distributions, and 3) report the accuracy of participating systems' normalizing shared normalized concepts between the test set and the Consumer Health Vocabulary, a vocabulary of lay medical terms. RESULTS: The best systems submitted by the five participating teams performed with accuracies ranging from 43 to 72 %. A majority sense baseline approach achieved the second best performance. The performance of participating systems for normalizing short forms with two or more senses with low ambiguity (majority sense greater than 80 %) ranged from 52 to 78 % accuracy, with two or more senses with moderate ambiguity (majority sense between 50 and 80 %) ranged from 23 to 57 % accuracy, and with two or more senses with high ambiguity (majority sense less than 50 %) ranged from 2 to 45 % accuracy. With respect to the ShARe test set, 69 % of short form annotations contained common concept unique identifiers with the Consumer Health Vocabulary. For these 2594 possible annotations, the performance of participating systems ranged from 50 to 75 % accuracy. CONCLUSION: Short form normalization continues to be a challenging problem. Short form normalization systems perform with moderate to reasonable accuracies. The Consumer Health Vocabulary could enrich its knowledge base with missed concept unique identifiers from the ShARe test set to further support patient understanding of unfamiliar medical terms. PMID- 27370274 TI - [Not Available]. PMID- 27370275 TI - [Not Available]. PMID- 27370276 TI - [Not Available]. PMID- 27370277 TI - [Not Available]. PMID- 27370278 TI - [Not Available]. PMID- 27370279 TI - [Not Available]. PMID- 27370280 TI - [Not Available]. PMID- 27370281 TI - [Not Available]. PMID- 27370282 TI - [Not Available]. PMID- 27370284 TI - [Not Available]. PMID- 27370283 TI - [Not Available]. PMID- 27370285 TI - [Not Available]. PMID- 27370287 TI - [Not Available]. PMID- 27370286 TI - [Not Available]. PMID- 27370288 TI - [Not Available]. PMID- 27370289 TI - [Not Available]. PMID- 27370291 TI - [Not Available]. PMID- 27370292 TI - [Not Available]. PMID- 27370290 TI - [Not Available]. PMID- 27370293 TI - [Not Available]. PMID- 27370295 TI - [Not Available]. PMID- 27370294 TI - [Not Available]. PMID- 27370296 TI - [Not Available]. PMID- 27370298 TI - [Not Available]. PMID- 27370297 TI - [Not Available]. PMID- 27370299 TI - [Not Available]. PMID- 27370300 TI - [Not Available]. PMID- 27370302 TI - [Not Available]. PMID- 27370301 TI - [Not Available]. PMID- 27370303 TI - [Not Available]. PMID- 27370304 TI - [Not Available]. PMID- 27370305 TI - [Not Available]. PMID- 27370308 TI - Evaluating the Surgeons' Perception of Difficulties of Two Techniques to Perform STARR for Obstructed Defecation Syndrome: A Multicenter Randomized Trial. AB - BACKGROUND: After initial enthusiasm in the use of a dedicated curved stapler (CCS-30 Contour Transtar) to perform stapled transanal rectal resection (STARR) for obstructed defecation syndrome (ODS), difficulties have emerged in this surgical technique. OBJECTIVE: First, to compare surgeons' perception of difficulties of STARR performed with only Transtar versus STARR performed with the combined use of linear staplers and Transtar to cure ODS associated with large internal prolapse and rectocele; second, to compare the postoperative incidence of the urge to defecate between the 2 STARR procedures. DESIGN AND SETTING: An Italian multicenter randomized trial involving 25 centers of colorectal surgery. PATIENTS: Patients with obstructed defecation syndrome and rectocele or rectal intussusception, treated between January and December 2012. INTERVENTIONS: Participants were randomly assigned to undergo STARR with a curved alone stapler (CAS group) or with the combined use of linear and curved staplers (LCS group). MAIN OUTCOME MEASURES: Primary end-points were the evaluation of surgeons' perception of difficulties score and the incidence of the "urge to defecate" at 3-month follow up. Secondary end-points included duration of hospital stay, rates of early and late complications, incidence of "urge to defecate" at 6 and 12 months, success of the procedures at 12 months of follow up. RESULTS: Of 771 patients evaluated, 270 patients (35%) satisfied the criteria. Follow-up data were available for 254 patients: 128 patients (114 women) in the CAS group (mean age, 52.1; range, 39-70 years) and 126 (116 women) in LCS group (mean age, 50.7 years; range, 41-75 years). The mean surgeons' perception score, was 15.36 (SD, 3.93) in the CAS group and 12.26 (SD, 4.22) in the LCS group (P < .0001; 2-sample t test). At 3-month follow-up, urge to defecate was observed in 18 (14.6%) CAS group patients and in 13 (10.7%) LCS group patients (P = .34; Fisher's exact test). These values drastically decrease at 6 months until no urge to defecate in all patients at 12 months was observed. At 12-month follow-up, a successful outcome was achieved in 100 (78.1%) CAS group patients and in 105 (83.3%) LCS group patients (P = .34; Fisher's exact test). No significant differences between groups were observed in the hospital stay and rates of early or late complications occurring after STARR. CONCLUSIONS: STARR with Transtar associated with prior decomposition of prolapse, using linear staplers, seems to be less difficult than that without decomposition. Both procedures appear to be safe and effective in the treatment of obstructed defecation syndrome resulting in similar success rates and complications. PMID- 27370309 TI - Evaluation of pollution of Ganga River water using fish as bioindicator. AB - Ganga River, life line of millions of people got heavily polluted due to uncontrolled anthropogenic activities. To monitor the effect of pollution of the river on its aquatic life, a field study was conducted by analyzing the different biomarker enzymes and biochemical parameters in the various tissues (muscles, liver, gills, kidney, brain, and skin) of the Indian major carp Labeo rohita collected from the River Ganga from different study sites of Varanasi district. Activities of antioxidant enzymes, e.g., superoxide dismutase, catalase, and level of lipid peroxidation were found to be higher in the fish collected from the river showing pollutant-induced oxidative stress in the fish. Disturbed health status of the river fish was also manifested by increased activities of aspartate amino transferase, alanine amino transferase, and alkaline phosphatase. Concentration of nutritionally important biomolecules (proteins, lipids, and moisture) and energy value were also found to be significantly lower in the tissues of the River fish indicating its decreased nutritional value due to oxidative stress caused by different pollutants. PMID- 27370311 TI - Effect of the timing of admission upon patient prognosis in the Intensive Care Unit: (On-hours versus off-hours) and diurnal variation. PMID- 27370310 TI - Prognostic significance of p53 expression in patients with esophageal cancer: a meta-analysis. AB - BACKGROUND: The prognostic value of p53 protein expression in esophageal cancer has been evaluated, but the results remain inconclusive and no consensus has yet been achieved. This meta-analysis was conducted to quantitatively assess the prognostic significance of p53 expression in esophageal cancer. METHODS: Publications that assessed the clinical or prognostic significance of p53 expression in esophageal cancer and were published before July 1, 2015 were identified by searching the PubMed and EMBASE databases. A meta-analysis was performed to clarify the association between p53 expression and the clinical outcomes. RESULTS: A total of 36 publications met the criteria and included 4577 cases. Analysis of these data showed that p53 expression in esophageal cancer was significantly associated with poorer 5-year survival (RR = 1.30, 95 % CI: 1.11 1.51, P = 0.0008). Subgroup analyses according to histological type, continent of the patients, and cut-off value revealed the similar results. The results also indicated that p53 expression was highly associated with advanced TNM stages (I/II vs. III/IV, OR = 0.74, 95 % CI: 0.55-0.99, P = 0.04), lymph node metastasis (OR = 0.77, 95 % CI: 0.66-0.90, P = 0.001), and distant metastasis (OR = 0.46, 95 % CI: 0.26-0.80, P = 0.006). However, p53 expression in the included studies was not significantly associated with tumor size (<= 5 cm vs. > 5 cm, OR = 1.13, 95 % CI: 0.92-1.40, P = 0.24), tumor location (upper + middle vs. lower, OR = 0.91, 95 % CI: 0.70-1.17, P = 0.45), grade of differentiation (well + moderate vs. poor, OR = 1.10, 95 % CI: 0.90-1.34, P = 0.35), and the depth of invasion (T1/T2 vs. T3/T4, OR = 0.86, 95 % CI: 0.71-1.03, P = 0.09). CONCLUSIONS: This meta-analysis showed that p53 expression may be a useful biomarker for predicting poorer prognosis in patients with esophageal cancer. PMID- 27370312 TI - Conflicts of interest in the new consensus based definition of sepsis and septic shock (sepsis-3). PMID- 27370313 TI - Species interactions and plant polyploidy. AB - Polyploidy is a common mode of speciation that can have far-reaching consequences for plant ecology and evolution. Because polyploidy can induce an array of phenotypic changes, there can be cascading effects on interactions with other species. These interactions, in turn, can have reciprocal effects on polyploid plants, potentially impacting their establishment and persistence. Although there is a wealth of information on the genetic and phenotypic effects of polyploidy, the study of species interactions in polyploid plants remains a comparatively young field. Here we reviewed the available evidence for how polyploidy may impact many types of species interactions that range from mutualism to antagonism. Specifically, we focused on three main questions: (1) Does polyploidy directly cause the formation of novel interactions not experienced by diploids, or does it create an opportunity for natural selection to then form novel interactions? (2) Does polyploidy cause consistent, predictable changes in species interactions vs. the evolution of idiosyncratic differences? (3) Does polyploidy lead to greater evolvability in species interactions? From the scarce evidence available, we found that novel interactions are rare but that polyploidy can induce changes in pollinator, herbivore, and pathogen interactions. Although further tests are needed, it is likely that selection following whole-genome duplication is important in all types of species interaction and that there are circumstances in which polyploidy can enhance the evolvability of interactions with other species. PMID- 27370314 TI - Critical factors in the establishment of allopolyploids. AB - PREMISE OF THE STUDY: The growth and spread of new polyploid populations have been explained in terms of fitness advantages over their diploid progenitors. However, a fitness advantage is not sufficient to insure the establishment of a polyploid; it must also overcome the obstacles of demographic stochasticity and minority disadvantage. Several studies have addressed the population dynamics of autopolyploids, but the present study is the first to consider allopolyploids, which are affected by more factors than autopolyploids. METHODS: We constructed a population dynamic model of four types of plants (two parent species, hybrids, allopolyploids) that also included an explicit breeding system. KEY RESULTS: The numbers of plants of each type were the most important factors determining whether the new allopolyploid would become established. More polyploid plants greatly increased the likelihood of polyploid persistence. More plants of the parent species and more hybrids resulted in more polyploids being produced. The model parameters with the most effect on polyploid establishment were potential population size (K), individual plant fecundity, and niche separation (alpha). The most important breeding system parameters were selfing rates, which mitigated minority disadvantage imposed by pollen limitation. CONCLUSIONS: The importance of population sizes, and the parameters that controlled them, in overcoming demographic stochasticity parallels the well-recognized role of propagule pressure in determining the success of invasive species. We modeled the establishment of a new allopolyploid; analogous considerations would affect the establishment of a new autopolyploid. The critical role of population sizes in polyploid establishment should be more widely recognized. PMID- 27370315 TI - How to be a seXY plant model: A holistic view of sex-chromosome research. PMID- 27370317 TI - [Not Available]. PMID- 27370318 TI - [Not Available]. PMID- 27370316 TI - Role of EEG background activity, seizure burden and MRI in predicting neurodevelopmental outcome in full-term infants with hypoxic-ischaemic encephalopathy in the era of therapeutic hypothermia. AB - OBJECTIVE: To investigate the role of EEG background activity, electrographic seizure burden, and MRI in predicting neurodevelopmental outcome in infants with hypoxic-ischaemic encephalopathy (HIE) in the era of therapeutic hypothermia. METHODS: Twenty-six full-term infants with HIE (September 2011-September 2012), who had video-EEG monitoring during the first 72 h, an MRI performed within the first two weeks and neurodevelopmental assessment at two years were evaluated. EEG background activity at age 24, 36 and 48 h, seizure burden, and severity of brain injury on MRI, were compared and related to neurodevelopmental outcome. RESULTS: EEG background activity was significantly associated with neurodevelopmental outcome at 36 h (p = 0.009) and 48 h after birth (p = 0.029) and with severity of brain injury on MRI at 36 h (p = 0.002) and 48 h (p = 0.018). All infants with a high seizure burden and moderate-severe injury on MRI had an abnormal outcome. The positive predictive value (PPV) of EEG for abnormal outcome was 100% at 36 h and 48 h and the negative predictive value (NPV) was 75% at 36 h and 69% at 48 h. The PPV of MRI was 100% and the NPV 85%. The PPV of seizure burden was 78% and the NPV 71%. CONCLUSION: Severely abnormal EEG background activity at 36 h and 48 h after birth was associated with severe injury on MRI and abnormal neurodevelopmental outcome. High seizure burden was only associated with abnormal outcome in combination with moderate-severe injury on MRI. PMID- 27370319 TI - [Not Available]. PMID- 27370320 TI - [Not Available]. PMID- 27370321 TI - [Not Available]. PMID- 27370322 TI - [Not Available]. PMID- 27370323 TI - [Not Available]. PMID- 27370324 TI - [Not Available]. PMID- 27370325 TI - [Not Available]. PMID- 27370326 TI - Mucopolysaccharidosis VI in cats - clarification regarding genetic testing. AB - The release of new DNA-based diagnostic tools has increased tremendously in companion animals. Over 70 different DNA variants are now known for the cat, including DNA variants in disease-associated genes and genes causing aesthetically interesting traits. The impact genetic tests have on animal breeding and health management is significant because of the ability to control the breeding of domestic cats, especially breed cats. If used properly, genetic testing can prevent the production of diseased animals, causing the reduction of the frequency of the causal variant in the population, and, potentially, the eventual eradication of the disease. However, testing of some identified DNA variants may be unwarranted and cause undo strife within the cat breeding community and unnecessary reduction of gene pools and availability of breeding animals. Testing for mucopolysaccharidosis Type VI (MPS VI) in cats, specifically the genetic testing of the L476P (c.1427T>C) and the D520N (c.1558G>A) variants in arylsulfatase B (ARSB), has come under scrutiny. No health problems are associated with the D520N (c.1558G>A) variant, however, breeders that obtain positive results for this variant are speculating as to possible correlation with health concerns. Birman cats already have a markedly reduced gene pool and have a high frequency of the MPS VI D520N variant. Further reduction of the gene pool by eliminating cats that are heterozygous or homozygous for only the MPS VI D520N variant could lead to more inbreeding depression effects on the breed population. Herein is debated the genetic testing of the MPS VI D520N variant in cats. Surveys from different laboratories suggest the L476P (c.1427T>C) disease associated variant should be monitored in the cat breed populations, particularly breeds with Siamese derivations and outcrosses. However, the D520N has no evidence of association with disease in cats and testing is not recommended in the absence of L476P genotyping. Selection against the D520N is not warranted in cat populations. More rigorous guidelines may be required to support the genetic testing of DNA variants in all animal species. PMID- 27370329 TI - [Not Available]. PMID- 27370328 TI - [Not Available]. PMID- 27370327 TI - Exploring the Use of Information and Communication Technology by People With Mood Disorder: A Systematic Review and Metasynthesis. AB - BACKGROUND: There is a growing body of evidence relating to how information and communication technology (ICT) can be used to support people with physical health conditions. Less is known regarding mental health, and in particular, mood disorder. OBJECTIVE: To conduct a metasynthesis of all qualitative studies exploring the use of ICTs by people with mood disorder. METHODS: Searches were run in eight electronic databases using a systematic search strategy. Qualitative and mixed-method studies published in English between 2007 and 2014 were included. Thematic synthesis was used to interpret and synthesis the results of the included studies. RESULTS: Thirty-four studies were included in the synthesis. The methodological design of the studies was qualitative or mixed methods. A global assessment of study quality identified 22 studies as strong and 12 weak with most having a typology of findings either at topical or thematic survey levels of data transformation. A typology of ICT use by people with mood disorder was created as a result of synthesis. CONCLUSIONS: The systematic review and metasynthesis clearly identified a gap in the research literature as no studies were identified, which specifically researched how people with mood disorder use mobile ICT. Further qualitative research is recommended to understand the meaning this type of technology holds for people. Such research might provide valuable information on how people use mobile technology in their lives in general and also, more specifically, how they are being used to help with their mood disorders. PMID- 27370330 TI - [Not Available]. PMID- 27370332 TI - [Not Available]. PMID- 27370333 TI - [Not Available]. PMID- 27370331 TI - [Not Available]. PMID- 27370334 TI - [Not Available]. PMID- 27370336 TI - [Not Available]. PMID- 27370335 TI - [Not Available]. PMID- 27370337 TI - [Not Available]. PMID- 27370339 TI - [Not Available]. PMID- 27370338 TI - [Not Available]. PMID- 27370340 TI - [Not Available]. PMID- 27370341 TI - [Not Available]. PMID- 27370342 TI - [Not Available]. PMID- 27370343 TI - New Horizons in the Development of Novel Needle-Free Immunization Strategies to Increase Vaccination Efficacy. AB - The young twenty-first century has already brought several medical advances, such as a functional artificial human liver created from stem cells, improved antiviral (e.g., against HIV) and cancer (e.g., against breast cancer) therapies, interventions controlling cardiovascular diseases, and development of new and optimized vaccines (e.g., HPV vaccine). However, despite this substantial progress and the achievements of the last century, humans still suffer considerably from diseases, especially from infectious diseases. Thus, almost one fourth of all deaths worldwide are caused directly or indirectly by infectious agents. Although vaccination has led to the control of many diseases, including smallpox, diphtheria, and tetanus, emerging diseases are still not completely contained. Furthermore, pathogens such as Bordetella pertussis undergo alterations making adaptation of the respective vaccine necessary. Moreover, insufficient implementation of vaccination campaigns leads to re-emergence of diseases which were believed to be already under control (e.g., poliomyelitis). Therefore, novel vaccination strategies need to be developed in order to meet the current challenges including lack of compliance, safety issues, and logistic constraints. In this context, mucosal and transdermal approaches constitute promising noninvasive vaccination strategies able to match these demands. PMID- 27370344 TI - Epidemiology of Staphylococcus aureus Nasal Carriage Patterns in the Community. AB - Staphylococcus aureus (S. aureus) is a Gram-positive opportunistic pathogen that colonizes frequently and asymptomatically the anterior nares of humans and animals. It can cause different kinds of infections and is considered to be an important nosocomial pathogen. Nasal carriage of S. aureus can be permanent or intermittent and may build the reservoir for autogenous infections and cross transmission to other individuals. Most of the studies on the epidemiology of S. aureus performed in the past were focused on the emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) in healthcare settings. There are, however, a number of more recent epidemiological studies have aimed at analysing carriage patterns over time in the community settings providing new insights on risk factors for colonization and important data for the development of strategies to prevent infections. This chapter aims to give a review of current epidemiological studies on S. aureus carriage patterns in the general community and put them into perspective with recent, yet unpublished, investigations on the S. aureus epidemiology in the general population in northern Germany. PMID- 27370345 TI - Chlamydia trachomatis as the Cause of Infectious Infertility: Acute, Repetitive or Persistent Long-Term Infection? AB - Chlamydia trachomatis is the most frequently detected agent of sexually transmitted infections worldwide. Infection of the lower female genital tract (FGT) can cause cervicitis and if ascending to the upper FGT may result in serious sequelae such as pelvic inflammatory disease (PID), salpingitis and tubal factor infertility (TFI). The factors leading to this complication are still not completely understood. We elaborate four different models for host-pathogen interactions in C. trachomatis infections that may promote disease development: (1) acute infection, (2) repeated infections, (3) chronic/persistent infections and (4) non-inflammatory colonization. Whereas experimental data exist for all of these models in vitro, ex vivo and in vivo, we were interested in seeing what clinical evidence we have supporting one or the other model. We particularly focused on data that favour the one or the other model for TFI development in C. trachomatis infection and speculate on future studies that could integrate in vitro findings for a better characterization of the situation in vivo. PMID- 27370347 TI - Correction to: "The Affinity of D2-Like Dopamine Receptor Antagonists Determines the Time to Maximal Effect on Cocaine Self-Administration.". PMID- 27370348 TI - Re: Norman AB, Tabet MR, Norman MK, and Tsibulsky VL (2014) Maintained Cocaine Self-Administration Is Determined by Quantal Responses: Implications for the Measurement of Antagonist Potency. J Pharmacol Exp Ther 348:311-315; doi:10.1124/jpet.113.210690. PMID- 27370349 TI - [Not Available]. PMID- 27370350 TI - [Not Available]. PMID- 27370351 TI - [Not Available]. PMID- 27370346 TI - Immunopathogenesis of Chlamydial Infections. AB - Chlamydial infections lead to a number of clinically relevant diseases and induce significant morbidity in human populations. It is generally understood that certain components of the host immune response to infection also mediate such disease pathologies. A clear understanding of pathogenic mechanisms will enable us to devise better preventive and/or intervention strategies to mitigate the morbidity caused by these infections. Over the years, numerous studies have been conducted to explore the immunopathogenic mechanisms of Chlamydia-induced diseases of the eye, reproductive tract, respiratory tract, and cardiovascular systems. In this article, we provide an overview of the diseases caused by Chlamydia, animal models used to study disease pathology, and a historical context to the efforts to understand chlamydial pathogenesis. Furthermore, we discuss recent findings regarding pathogenesis, with an emphasis on the role of the adaptive immune response in the development of chlamydial disease sequelae. Finally, we summarize the key insights obtained from studies of chlamydial pathogenesis and avenues that remain to be explored in order to inform the next steps of vaccine development against chlamydial infections. PMID- 27370352 TI - [Not Available]. PMID- 27370353 TI - [Not Available]. PMID- 27370354 TI - [Not Available]. PMID- 27370355 TI - [Not Available]. PMID- 27370356 TI - [Not Available]. PMID- 27370358 TI - Fertility preservation in female oncology patients: the influence of the type of cancer on ovarian stimulation response. AB - STUDY QUESTION: Does the type of cancer influence on the ovarian response to stimulation for fertility preservation (FP) in female oncology patients? SUMMARY ANSWER: Patients with gynaecological cancer have less number of retrieved mature oocytes compared with haematological and breast cancer patients. WHAT IS KNOWN ALREADY: Concerns about the impact of cancer therapy on future fertility have been raised and FP has become an important component in cancer management. Previous studies analysing FP results in cancer patients have shown conflicting findings. STUDY DESIGN, SIZE, DURATION: This was a retrospective analytical study performed in the Centre for Reproductive Medicine, at St Bartholomew's Hospital, between January 2000 and December 2014. The aim of this study was to analyse the response to ovarian stimulation in cancer patients before undergoing cancer treatment and to determine whether any difference can be attributed to underlying cancer diagnosis. We also report the pregnancy outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 531 female patients recently diagnosed with cancer were referred for counselling on FP. A total of 306 patients underwent ovarian stimulation for oocyte or embryo cryopreservation. We compared the baseline characteristics and ovarian response in five main subgroups: breast cancer, haematological cancer, gynaecological cancer, gastrointestinal cancer and others. The primary outcome was the total number of mature oocytes retrieved and pregnancy outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: The main cancer diagnosis was breast cancer with 145 patients (47.4%); 79 patients (25.8%) had haematological malignancies; 42 (13.7%) had gynaecological malignancies; 20 (6.5%) had gastrointestinal cancer and 20 (6.5%) had other types of cancer. Patients with breast cancer were older (P < 0.001). Patients with haematological malignancies had higher number of mature oocytes retrieved (P = 0.003). The number of mature oocytes retrieved was lower in patients with gynaecological malignancy compared with haematological and breast cancer patients (P = 0.005 and P = 0.045, respectively). The fertilization rate and the number of cycles cancelled were comparable between all the groups. Thirty-two embryo transfer cycles have been done in 22 patients who have returned to attempt pregnancy. Pregnancy rate per transfer cycle was 43.75%, and cumulative pregnancy rate per patient was 54.5%. Live birth rate per patient was 22.72%. LIMITATIONS, REASONS FOR CAUTION: Apart from the retrospective nature of the study, patients were included over the period of 15 years, and over that time technology has changed and protocols have evolved. The results obtained from subcategory analyses should be interpreted with caution, as in each subgroup there are different types of malignancies with different number of patients in different age groups. Different ovarian stimulation protocols were applied. Only a few patients have come back to attempt pregnancy after being cured from their disease. We do not have follow-up data on these patients; as a result, we are not able to report the survival rate and the reason for non-return for embryo transfer. In addition, we cannot report information on spontaneous conceptions and births. Slow freezing used for embryo cryopreservation, high miscarriage rate and low live birth rate per transfer are other limitations of this study. WIDER IMPLICATIONS OF THE FINDINGS: The current study is the largest series analysing each group of cancer separately and showing pregnancy outcomes in oncology patients undergoing FP. These results provide valuable information about the success of this technique in oncology patients. STUDY FUNDING/COMPETING INTEREST(S): The authors have not received any funding to support this study. There are no conflicts of interest to declare. PMID- 27370357 TI - Effects of yoga in adults with type 2 diabetes mellitus: A meta-analysis. AB - AIMS/INTRODUCTION: A meta-analysis was carried out to evaluate the efficacy of yoga in adults with type 2 diabetes mellitus. MATERIALS AND METHODS: The PubMed, EMBASE and Cochrane databases were searched to obtain eligible randomized controlled trials. The primary outcome was fasting blood glucose, and the secondary outcomes included glycosylated hemoglobin A1c, total cholesterol, high density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride and postprandial blood glucose. Weighted mean differences and 95% confidence intervals (CIs) were calculated. The I2 statistic represented heterogeneity. RESULTS: A total of 12 randomized controlled trials with a total of 864 patients met the inclusion criteria. The pooled weighted mean differences were -23.72 mg/dL (95% CI -37.78 to -9.65; P = 0.001; I2 = 82%) for fasting blood glucose and -0.47% (95% CI -0.87 to -0.07; P = 0.02; I2 = 82%) for hemoglobin A1c. The weighted mean differences were -17.38 mg/dL (95% CI -27.88 to -6.89; P = 0.001; I2 = 0%) for postprandial blood glucose, -18.50 mg/dL (95% CI -29.88 to 7.11; P = 0.001; I2 = 75%) for total cholesterol, 4.30 mg/dL (95% CI 3.25 to 5.36; P < 0.00001; I2 = 10%) for high-density lipoprotein cholesterol, -12.95 mg/dL (95% CI -18.84 to -7.06; P < 0.0001; I2 = 37%) for low-density lipoprotein cholesterol and -12.57 mg/dL (95% CI -29.91 to 4.76; P = 0.16; I2 = 48%) for triglycerides. CONCLUSIONS: The available evidence suggests that yoga benefits adult patients with type 2 diabetes mellitus. However, considering the limited methodology and the potential heterogeneity, further studies are necessary to support our findings and investigate the long-term effects of yoga in type 2 diabetes mellitus patients. PMID- 27370359 TI - RCT to evaluate the influence of adjuvant medical treatment of peritoneal endometriosis on the outcome of IVF. AB - STUDY QUESTION: Does a 3-month adjuvant hormonal treatment of mild peritoneal endometriosis after laparoscopic surgery influence the outcome of IVF stimulation in terms of number of mature oocytes obtained per cycle? SUMMARY ANSWER: Complementary medical treatment of mild peritoneal endometriosis does not influence the number of oocytes per treatment cycle. WHAT IS KNOWN ALREADY: Endometriosis is a disease known to be related to infertility. However, the influence of superficial endometriosis-and its treatment-is still a matter of debate. STUDY DESIGN, SIZE, DURATION: A prospective controlled, randomized, open label trial was performed between February 2012 and March 2014 and embryological and clinical outcomes were measured. Patients with laparoscopically diagnosed peritoneal endometriosis (n= 120) were treated by laser surgery after which they were sequentially randomized by computer-generated allocation to one of the two groups. The primary outcome of the trial was the number of Metaphase II (MII) oocytes. Sample size was chosen to detect a difference of two MII oocytes with a power of 80%. The control group (Group B) received the classical long protocol IVF stimulation, whereas the research group (Group A) had an additional pituitary suppression, of 3 months using a long-acting GnRH agonist, prior to IVF. PARTICIPANTS/ MATERIALS, SETTING, METHODS: A total of 120 patients were included in the study, 61 of them in the study group and 59 patients in the control group. One patient of the control group was lost to follow up leading to 58 evaluable patients. MAIN RESULTS AND THE ROLE OF CHANCE: There was no difference in terms of the number of MII oocytes obtained per cycle: 8.2 in both groups (difference in MII between A and B: 0.07 [-1.89; 2.04] 95% confidence interval (CI)). Pregnancy rate did not differ, being 39.3% for Group A (24 out of 61 patients) versus 39.7% for Group B (23 out of 58 patients) (95% CI around difference in pregnancy rate between A and B: -0.31% [-17.96%; 17.86%]). However, a significantly (P = 0.025) lower dose of FSH (2561 IU for Group A and 2303 IU for Group B, 95% CI around difference in FSH between B and A: -258.6 IU [-483.4 IU; 33.8 IU]) and a significantly (P = 0.004) shorter stimulation period (Group A 12.3 days and Group B 11.3 days, 95% CI around difference in stimulation period between B and A: -1.03 days [-1.73 days; -0.33 days]) were needed to reach adequate follicle maturation in the control group. LIMITATIONS, REASON FOR CAUTION: The validity of this study is limited to mild peritoneal endometriosis, and does not apply to ovarian endometriosis, which is also commonly seen in infertility patients. WIDER IMPLICATIONS OF THE FINDINGS: There is no indication for complementary medical treatment of peritoneal endometriosis in terms of IVF outcome. On the contrary, stimulation takes longer and requires a higher amount of medication. STUDY FUNDING/COMPETING INTERESTS: There was no external funding for this clinical trial in the IVF Center, AZ Jan Palfijn, Ghent. There are no competing interests to declare. TRIAL REGISTRATION NUMBER: EudraCT nr: 2012 000784-25. TRIAL REGISTRATION DATE: First registration on 29 February 2012 and re entered on 23 August 2012, NCT01682642 (due to a change of staff). DATE OF FIRST PATIENT'S ENROLLMENT: 8 March 2012. PMID- 27370360 TI - Multimodal communication, mismatched messages and the effects of turbidity on the antipredator behavior of the Barton Springs salamander, Eurycea sosorum. AB - Prey may use multiple sensory channels to detect predators, whose cues may differ in altered sensory environments, such as turbid conditions. Depending on the environment, prey may use cues in an additive/complementary manner or in a compensatory manner. First, to determine whether the purely aquatic Barton Springs salamander, Eurycea sosorum, show an antipredator response to visual cues, we examined their activity when exposed to either visual cues of a predatory fish (Lepomis cyanellus) or a non-predatory fish (Etheostoma lepidum). Salamanders decreased activity in response to predator visual cues only. Then, we examined the antipredator response of these salamanders to all matched and mismatched combinations of chemical and visual cues of the same predatory and non predatory fish in clear and low turbidity conditions. Salamanders decreased activity in response to predator chemical cues matched with predator visual cues or mismatched with non-predator visual cues. Salamanders also increased latency to first move to predator chemical cues mismatched with non-predator visual cues. Salamanders decreased activity and increased latency to first move more in clear as opposed to turbid conditions in all treatment combinations. Our results indicate that salamanders under all conditions and treatments preferentially rely on chemical cues to determine antipredator behavior, although visual cues are potentially utilized in conjunction for latency to first move. Our results also have potential conservation implications, as decreased antipredator behavior was seen in turbid conditions. These results reveal complexity of antipredator behavior in response to multiple cues under different environmental conditions, which is especially important when considering endangered species. PMID- 27370361 TI - Swimming-based pica in rats. AB - We have recently demonstrated that voluntary or forced running in activity wheels yields pica behavior (kaolin clay intake) in rats (Nakajima, 2016; Nakajima and Katayama, 2014). The present study provides experimental evidence that a single 40-min session of swimming in water also generates pica in rats, while showering rats with water does not produce such behavior. Because kaolin intake has been regarded as a measure of nausea in rats, this finding suggests that swimming activity, as well as voluntary or forced running, induces nausea in rats. PMID- 27370362 TI - Veterinary Ophthalmology - Feline Special Issue. PMID- 27370363 TI - Comparison between Pentacam-HR and optical coherence tomographycentral corneal thickness measurements in healthy feline eyes. AB - OBJECTIVES: To measure the central corneal thickness (CCT) in healthy feline eyes with Scheimpflug imaging (Pentacam, Pentacam((r)) -HR) and to compare these values with those obtained with spectral-domain optical coherence tomography (OCT, Optovue((r)) iVue). ANIMALS STUDIED: Thirty one sedated Domestic Short haired cats. PROCEDURES: Two repeated CCT measurements were obtained from both eyes using Pentacam measured at the pupil center and corneal apex (CCTpupil and CCTapex ) and using SD-OCT (CCTOCT ). Agreement between the imaging modalities for CCT and intradevice repeatability was evaluated with Bland-Altman analysis. Mixed modeling was used to test for a difference between methods. RESULTS: The calculated mean +/- SD CCT was CCTOCT = 584.93 +/- 39.05 MUm, CCTpupil = 608.25 +/- 47.26 MUm, and CCTapex = 606.41 +/- 44.18 MUm. There was a statistically significant difference between CCTOCT vs. CCTpupil (P < 0.0007) and CCTOCT vs. CCTapex (P < 0.0003) (n = 59 eyes). The 95% limits of agreement (LoA) for CCTOCT vs. CCTpupil was (-89.57 MUm, 40.04 MUm) and for CCTOCT vs. CCTapex was (-79.62 MUm, 33.79 MUm) (n = 59 eyes). 95% LoA between repeated CCT measurements by SD OCT was (-10.23 MUm, 9.32 MUm) and by Pentacam was (-22.66 MUm, 18.30 MUm) at pupil and (-15.81 MUm, 16.17 MUm) at corneal apex (n = 11 eyes). CONCLUSIONS: SD OCT and Pentacam provide excellent CCT measurement repeatability. Pentacamapex is our recommended clinical setting for use of the Pentacam. The level of agreement between SD-OCT and Pentacam for CCT is good. PMID- 27370364 TI - Dacryops of the Third Eyelid in a cat. AB - A 9-month-old female Domestic Short-haired cat was presented with a mass of three month duration at the base of the third eyelid of the right eye (OD). Fine-needle aspiration was carried out at another clinic, revealing clear fluid. The mass soon reformed, and the cat was referred. Ophthalmic examination revealed a pale pink, smooth, oval mass under the conjunctiva on the anterior aspect of the third eyelid. Surgical removal of the mass was performed. Histopathology revealed a large dilated cyst together with a number of small cysts lined by simple cuboidal, and low squamous epithelium with some secretory cells. Dacryops of the third eyelid lacrimal gland was diagnosed. The eye healed uneventfully after surgery, and no recurrence was seen during one year of follow-up. PMID- 27370365 TI - p16 expression independent of human papillomavirus is associated with lower stage and longer disease-free survival in oral cavity squamous cell carcinoma. AB - There is limited information regarding the incidence of p16 expression, its association with human papillomavirus (HPV) and prognosis in oral cavity squamous cell carcinoma (OSCC). The role of p16 in OSCC is evaluated in 215 cases using tissue microarrays (TMAs). p16 immunohistochemistry and HPV in situ hybridisation were performed on TMAs following histopathology review of 215 patients with OSCC in the Sydney Head and Neck Cancer Institute database. Thirty-seven (17.2%) cases showed p16 expression without association with HPV. p16 expression significantly decreased with increasing pT category (p=0.002). p16 expression was associated with longer disease-specific survival on univariable analysis (p=0.044) but not on multivariable analysis adjusting for depth of invasion. Amongst patients receiving adjuvant radiotherapy, patients with p16 expression had significantly longer disease-free and overall survival. p16 expression was seen in early stage OSCCs and was associated with better survival following surgery and radiotherapy. While not an independent predictor of survival, p16 may mediate its effects by contributing to reduced proliferative capacity, leading to smaller tumour size and lower invasive potential. PMID- 27370367 TI - [Not Available]. PMID- 27370368 TI - [Not Available]. PMID- 27370366 TI - [Not Available]. PMID- 27370369 TI - [Not Available]. PMID- 27370370 TI - [Not Available]. PMID- 27370371 TI - [Not Available]. PMID- 27370373 TI - [Not Available]. PMID- 27370372 TI - [Not Available]. PMID- 27370374 TI - [Not Available]. PMID- 27370375 TI - [Not Available]. PMID- 27370376 TI - [Not Available]. PMID- 27370377 TI - [Not Available]. PMID- 27370378 TI - [Not Available]. PMID- 27370379 TI - [Not Available]. PMID- 27370380 TI - [Not Available]. PMID- 27370381 TI - [Not Available]. PMID- 27370382 TI - [Not Available]. PMID- 27370383 TI - [Not Available]. PMID- 27370384 TI - [Not Available]. PMID- 27370385 TI - [Not Available]. PMID- 27370386 TI - [Not Available]. PMID- 27370387 TI - [Not Available]. PMID- 27370388 TI - [Not Available]. PMID- 27370389 TI - [Not Available]. PMID- 27370390 TI - [Not Available]. PMID- 27370391 TI - What is healthy aging? PMID- 27370392 TI - Aging in cats: Common physical and functional changes. AB - PRACTICAL RELEVANCE: Aged pets comprise a significant proportion of the small animal veterinarian's patient population; in the USA, for example, it was estimated that over 20% of pet cats were 11 years of age or older in 2011. Certain changes associated with aging are neither positive nor negative, but others are less desirable, associated with illness, changes in mobility or the development of unwanted behaviors. These changes can greatly affect the health and wellbeing of the cat and have a tremendous impact on the owner. CLINICAL CHALLENGES: Regular veterinary examinations are essential for evaluating the health of older patients and for providing owners with guidance regarding optimal care. With the exception of overt disease, however, it is difficult to definitively determine if a cat is displaying changes that are appropriate for age or if they reflect an abnormal process or condition. GOALS: This is the first of two review articles in a Special Issue devoted to feline healthy aging. The goals of the project culminating in these publications included developing a working definition for healthy aging in feline patients and identifying clinical methods that can be used to accurately classify healthy aged cats. This first review provides a thorough, systems-based overview of common health-related changes observed in cats as they age. EVIDENCE BASE: There is a paucity of research in feline aging. The authors have drawn on expert opinion and available data in both the cat and other species. PMID- 27370393 TI - Evaluating aging in cats: How to determine what is healthy and what is disease. AB - PRACTICAL RELEVANCE: Many of the changes that occur with aging are not considered pathologic and do not negatively affect overall wellness or quality of life. Ruling out disease is essential, however, when attempting to determine whether an aged cat can be considered 'healthy'. A clear understanding of the normal and abnormal changes that are associated with aging in cats can help practitioners make decisions regarding medical management, feeding interventions and additional testing procedures for their aged patients. CLINICAL CHALLENGES: It can be difficult to determine if a cat is displaying changes that are appropriate for age. For example, healthy aged cats may have hematologic or serum biochemistry changes that differ from those of the general feline population. Assessment of behavioral health and cognitive changes, as well as auditory, olfactory and visual changes, can also be challenging in the aged patient. GOALS: This is the second of two review articles in a Special Issue devoted to feline healthy aging. The goals of the project culminating in these publications included developing a working definition for healthy aging in feline patients and identifying clinical methods that can be used to accurately classify healthy aged cats. This second review proposes criteria for assessing 'healthy aged cats'. EVIDENCE BASE: There is a paucity of research in feline aging. The authors draw on expert opinion and available data in both the cat and other species. PMID- 27370394 TI - News & Views. PMID- 27370395 TI - Prognostic relevance of epilepsy at presentation in lower-grade gliomas. PMID- 27370396 TI - Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. AB - BACKGROUND: Optimal treatment and precise classification for anaplastic glioma are needed. METHODS: The objective for long-term follow-up of NOA-04 is to optimize the treatment sequence for patients with anaplastic gliomas. Patients were randomized 2:1:1 to receive the standard radiotherapy (RT) (arm A), procarbazine, lomustine and vincristine (PCV) (arm B1), or temozolomide (TMZ) (arm B2). RESULTS: Primary endpoint was time-to-treatment-failure (TTF), defined as progression after 2 lines of therapy or any time before if no further therapy was administered. Exploratory analyses examined associations of molecular marker status with TTF, progression-free survival (PFS), and overall survival (OS). At 9.5 (95% CI: 8.6-10.2) years, no difference between arms (A vs B1/B2) was observed: median TTF (4.6 [3.4-5.1] y vs 4.4 [3.3-5.3) y), PFS (2.5 [1.3-3.5] y vs 2.7 [1.9-3.2] y), and OS (8 [5.5-10.3] y vs 6.5 [5.4-8.3] y). Oligodendroglial versus astrocytic histology-but more so the subgroups according to CpG island methylator phenotype (CIMP) and 1p/19q co-deletion status-revealed a strong prognostic value of CIMPpos with (CIMPcodel) versus without 1p/19 co-deletion (CIMPnon-codel) versus CIMPneg. but no differential efficacy of RT versus chemotherapy for any of the endpoints. PFS was better for PCV- than for TMZ treated patients with CIMPcodel tumors (HR B1 vs B2 0.39 [0.17-0.92], P = .031). In CIMPneg. tumors, hypermethylation of the O6-methyl-guanyl-DNA methyltransferase promoter (MGMT) provided a risk reduction for PFS with chemotherapy. CONCLUSIONS: There is no differential activity of primary chemotherapy versus RT in any subgroup of anaplastic glioma. Molecular diagnosis is superior to histology. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00717210. PMID- 27370397 TI - Inhibition of DNA damage repair by the CDK4/6 inhibitor palbociclib delays irradiated intracranial atypical teratoid rhabdoid tumor and glioblastoma xenograft regrowth. AB - BACKGROUND: Radiation therapy is the most commonly used postsurgical treatment for primary malignant brain tumors. Consequently, investigating the efficacy of chemotherapeutics combined with radiation for treating malignant brain tumors is of high clinical relevance. In this study, we examined the cyclin-dependent kinase 4/6 inhibitor palbociclib, when used in combination with radiation for treating human atypical teratoid rhabdoid tumor (ATRT) as well as glioblastoma (GBM). METHODS: Evaluation of treatment antitumor activity in vitro was based upon results from cell proliferation assays, clonogenicity assays, flow cytometry, and immunocytochemistry for DNA double-strand break repair. Interpretation of treatment antitumor activity in vivo was based upon bioluminescence imaging, animal subject survival analysis, and staining of tumor sections for markers of proliferation and apoptosis. RESULTS: For each of the retinoblastoma protein (RB)-proficient tumor models examined (2 ATRTs and 2 GBMs), one or more of the combination therapy regimens significantly (P < .05) outperformed both monotherapies with respect to animal subject survival benefit. Among the combination therapy regimens, concurrent palbociclib and radiation treatment and palbociclib treatment following radiation consistently outperformed the sequence in which radiation followed palbociclib treatment. In vitro investigation revealed that the concurrent use of palbociclib with radiation, as well as palbociclib following radiation, inhibited DNA double-strand break repair and promoted increased tumor cell apoptosis. CONCLUSIONS: Our results support further investigation and possible clinical translation of palbociclib as an adjuvant to radiation therapy for patients with malignant brain tumors that retain RB expression. PMID- 27370398 TI - CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone. AB - BACKGROUND: Patients with glioblastoma (GBM) have an overall median survival of 15 months despite multimodal therapy. These catastrophic survival rates are to be correlated to systematic relapses that might arise from remaining glioblastoma stem cells (GSCs) left behind after surgery. In this line, it has recently been demonstrated that GSCs are able to escape the tumor mass and preferentially colonize the adult subventricular zone (SVZ). At a distance from the initial tumor site, these GSCs might therefore represent a high-quality model of clinical resilience to therapy and cancer relapses as they specifically retain tumor initiating abilities. METHOD: While relying on recent findings that have validated the existence of GSCs in the human SVZ, we questioned the role of the SVZ niche as a potential GSC reservoir involved in therapeutic failure. RESULTS: Our results demonstrate that (i) GSCs located in the SVZ are specifically resistant to radiation in vivo, (ii) these cells display enhanced mesenchymal roots that are known to be associated with cancer radioresistance, (iii) these mesenchymal traits are specifically upregulated by CXCL12 (stromal cell-derived factor-1) both in vitro and in the SVZ environment, (iv) the amount of SVZ released CXCL12 mediates GBM resistance to radiation in vitro, and (v) interferes with the CXCL12/CXCR4 signalling system, allowing weakening of the tumor mesenchymal roots and radiosensitizing SVZ-nested GBM cells. CONCLUSION: Together, these data provide evidence on how the adult SVZ environment, through the release of CXCL12, supports GBM therapeutic failure and potential tumor relapse. PMID- 27370399 TI - Anticancer drug candidate CBL0137, which inhibits histone chaperone FACT, is efficacious in preclinical orthotopic models of temozolomide-responsive and resistant glioblastoma. AB - Background: The survival rate for patients with glioblastoma (GBM) remains dismal. New therapies targeting molecular pathways dysregulated in GBM are needed. One such clinical-stage drug candidate, CBL0137, is a curaxin, small molecules which simultaneously downregulate nuclear factor-kappaB (NF-KB) and activate p53 by inactivating the chromatin remodeling complex, Facilitates Chromatin Transcription (FACT). Methods: We used publicly available databases to establish levels of FACT subunit expression in GBM. In vitro, we evaluated the toxicity and effect of CBL0137 on FACT, p53, and NF-KB on U87MG and A1207 human GBM cells. In vivo, we implanted the cells orthotopically in nude mice and administered CBL0137 in various dosing regimens to assess brain and tumor accumulation of CBL0137, its effect on tumor cell proliferation and apoptosis, and on survival of mice with and without temozolomide (TMZ). Results: FACT subunit expression was elevated in GBM compared with normal brain. CBL0137 induced loss of chromatin-unbound FACT, activated p53, inhibited NF-KB-dependent transcription, and was toxic to GBM cells. The drug penetrated the blood-brain barrier and accumulated in orthotopic tumors significantly more than normal brain tissue. It increased apoptosis and suppressed proliferation in both U87MG and A1207 tumors. Intravenous administration of CBL0137 significantly increased survival in models of early- through late-stage TMZ-responsive and -resistant GBM, with a trend toward significantly increasing the effect of TMZ in TMZ responsive U87MG tumors. Conclusion: CBL0137 targets GBM according to its proposed mechanism of action, crosses the blood-brain barrier, and is efficacious in both TMZ-responsive and -resistant orthotopic models, making it an attractive new therapy for GBM. PMID- 27370401 TI - Non-AIDS Kaposi sarcoma in the external ear. PMID- 27370402 TI - Fluphenazine (oral) versus atypical antipsychotics for schizophrenia. AB - BACKGROUND: Fluphenazine is a typical antipsychotic drug from the phenothiazine group of antipsychotics. It has been commonly used in the treatment of schizophrenia, however, with the advent of atypical antipsychotic medications, use has declined over the years. OBJECTIVES: To measure the outcomes (both beneficial and harmful) of the clinical effectiveness, safety and cost effectiveness of oral fluphenazine versus atypical antipsychotics for schizophrenia. SEARCH METHODS: We searched the Cochrane Central Register of Studies (25 April 2013). For the economic search, we searched the Cochrane Schizophrenia Group Health Economic Database (CSzGHED) on 31 January 2014 SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing fluphenazine (oral) with any other oral atypical antipsychotics. DATA COLLECTION AND ANALYSIS: Review authors worked independently to inspect citations and assess the quality of the studies and to extract data. For homogeneous dichotomous data we calculated the risk ratio (RR) and 95% confidence interval (CI), and calculated the mean differences (MDs) for continuous data. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rate the quality of the evidence. MAIN RESULTS: Four studies randomising a total of 202 people with schizophrenia are included. Oral fluphenazine was compared with oral amisulpride, risperidone, quetiapine and olanzapine.Comparing oral fluphenazine with amisulpride, there was no difference between groups for mental state using the Brief Psychiatric Rating Scale (BPRS) (1 RCT, n = 57, MD 5.10 95% CI -2.35 to 12.55, very low-quality evidence), nor was there any difference in numbers leaving the study early for any reason (2 RCTs, n = 98, RR 1.19 95% CI 0.63 to 2.28, very low-quality evidence). More people required concomitant anticholinergic medication in the fluphenazine group compared to amisulpride (1 RCT, n = 36, RR 7.82 95% CI 1.07 to 57.26, very low quality evidence). No data were reported for important outcomes including relapse, changes in life skills, quality of life or cost-effectiveness.Comparing oral fluphenazine with risperidone, data showed no difference between groups for 'clinically important response' (1 RCT, n = 26, RR 0.67 95% CI 0.13 to 3.35, very low-quality evidence) nor leaving the study early due to inefficacy (1 RCT, n = 25, RR 1.08 95% CI 0.08 to 15.46, very low-quality evidence). No data were reported data for relapse; change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Once again there was no difference when oral fluphenazine was compared with quetiapine for clinically important response (1 RCT, n = 25, RR 0.62 95% CI 0.12 to 3.07, very low-quality evidence), nor leaving the study early for any reason (1 RCT, n = 25, RR 0.46 95% CI 0.05 to 4.46, very low-quality evidence). No data were reported for relapse; clinically important change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Compared to olanzapine, fluphenazine showed no superiority for clinically important response (1 RCT, n = 60, RR 1.33 95% CI 0.86 to 2.07, very low-quality evidence), in incidence of akathisia (1 RCT, n = 60, RR 3.00 95% CI 0.90 to 10.01, very low-quality evidence) or in people leaving the study early (1 RCT, n = 60, RR 3.00 95% CI 0.33 to 27.23, very low-quality evidence). No data were reported for relapse; change in life skills; quality of life; or cost effectiveness. AUTHORS' CONCLUSIONS: Measures of clinical response and mental state do not highlight differences between fluphenazine and amisulpride, risperidone, quetiapine or olanzapine. Largely measures of adverse effects are also unconvincing for substantive differences between fluphenazine and the newer drugs. All included trials carry a substantial risk of bias regarding reporting of adverse effects and this bias would have favoured the newer drugs. The four small short included studies do not provide much clear information about the relative merits or disadvantages of oral fluphenazine compared with newer atypical antipsychotics. PMID- 27370400 TI - Immune checkpoint blockade as a potential therapeutic target: surveying CNS malignancies. AB - BACKGROUND: Expression of programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) across glioma grades is undocumented, and their interactions with commonly expressed genetic and epigenetic alterations are undefined but nonetheless highly relevant to combinatorial treatments. METHODS: Patients with CNS malignancies were profiled by Caris Life Sciences from 2009 to 2016. Immunohistochemistry findings for PD-1 on tumor-infiltrating lymphocytes (TIL) and PD-L1 on tumor cells were available for 347 cases. Next-generation sequencing, pyrosequencing, immunohistochemistry, fragment analysis, and fluorescence in situ hybridization were used to determine isocitrate dehydrogenase 1 (IDH1), phosphatase and tensin homolog (PTEN), and tumor protein 53 mutational status, O(6)-DNA methylguanine-methyltransferase promoter methylation (MGMT-Me) status, PTEN expression, plus epidermal growth factor receptor variant III and 1p/19q codeletion status. RESULTS: PD-1+ TIL expression and grade IV gliomas were significantly positively correlated (odds ratio [OR]: 6.363; 95% CI: 1.263, 96.236)-especially in gliosarcomas compared with glioblastoma multiforme (P = .014). PD-L1 expression was significantly correlated with tumor grade with all PD-L1+ cases (n = 21) being associated with grade IV gliomas. PD-1+ TIL expression and PD-L1 expression were significantly correlated (OR: 5.209; 95% CI: 1.555, 20.144). Mutations of PTEN, tumor protein 53, BRAF, IDH1, and epidermal growth factor receptor or MGMT-Me did not associate with increased intratumoral expression of either PD-1+ TIL or PD-L1 in glioblastoma multiforme even before false discovery rate correction for multiple comparison. CONCLUSIONS: Targeting immune checkpoints in combination with other therapeutics based on positive biomarker selection will require screening of large patient cohorts. PMID- 27370403 TI - Dynamic IgG antibody response to immunodominant antigens of M. tuberculosis for active TB diagnosis in high endemic settings. AB - BACKGROUND: Even though various techniques have been developed for rapid diagnosis of tuberculosis (TB), still there is an immense need for a simple, cost effective, highly sensitive and specific test. Hence, one of the possibilities is identification of Mycobacterium tuberculosis specific antibodies in infected serum by using specific antigens. METHODS: We tested 10 recombinant M. tuberculosis antigens to evaluate IgG levels among Healthy control subjects (HCS), Healthy household contacts (HHC) and pulmonary TB patients (PTB) by ELISA. RESULTS: The median IgG levels specific to all the antigens are higher in PTB than HHC and HCS. Amongst single antigens, 38-kDa antigen has showed maximum sensitivity of 50% than any other antigens at 95.5% specificity. Among the two antigen combination, 38-kDa+Rv1860 has showed maximum sensitivity of 66.6% with specificity of 92.2%. The same antigen combination (38-kDa and Rv1860) predominantly identifies smear negative and culture positive TB patients with 68% sensitivity and 92.2% specificity. Most of the antigens have exhibited higher antibody titre in cavitary TB than non cavitary. With regard to latent TB infection (LTBI) identification, Rv1860 has exhibited maximum sensitivity of 53.3% with 95% specificity. CONCLUSIONS: IgG response to combination of recombinant mycobacterial antigens (38-kDa, Rv1860, Rv2204c and Rv0753c) presents good specificity with acceptable level of sensitivity for TB diagnosis. PMID- 27370404 TI - Activity and Safety of Sunitinib in Patients with Advanced Radioiodine Refractory Thyroid Carcinoma: A Retrospective Analysis of 57 Patients. AB - BACKGROUND: The aim of this study was to evaluate the effectiveness of sunitinib in patients with progressive radioiodine refractory (RAIR) thyroid cancer (TC). MATERIALS AND METHODS: A multicentric retrospective analysis was performed of patients treated in six TUmeurs THYroidiennes REFractaires participating centers. All patients with progressive RAIR TC who were treated with sunitinib outside a clinical trial between August 2007 and March 2015 were retrospectively and consecutively included. The primary endpoint was the overall response rate (ORR) and disease control rate >=6 months based on RECIST criteria. Secondary endpoints included evaluation of overall survival (OS) and progression-free survival (PFS) from the first dose of sunitinib. Primary and secondary endpoints were also evaluated according to treatment setting: first or second line of tyrosine kinase inhibitor (TKI). RESULTS: Fifty-seven patients (29 men; 50.8%), mean age 62.2 years (range 43-80 years) with progressive RAIR TC were included. Sunitinib was the first-line TKI treatment for 32 (56.1%) patients and the second-line TKI treatment for 25 (43.9%) patients. For all patients, according to RECIST criteria, ORR was 35.1% (20 patients) and disease control rate >=6 months was 68.4% (39 patients). No complete response was observed. Six (10.5%) patients showed disease progression. When sunitinib was used as first-line TKI therapy, ORR was 46.9% (15/32 patients), and disease control rate >=6 months was 75% (24/32 patients). When sunitinib was used as second-line TKI therapy, ORR was 20% (5/25 patients), and disease control rate >=6 months was 60% (15/25 patients). The median OS and PFS were 21.0 (range 15-29) and 10.2 months (range 6-13), respectively, for all patients. With sunitinib as first-line TKI-therapy, median OS and PFS was 30.0 (range 19.0-53.0) and 15 (range 7.0-21.0) months, respectively. As second-line therapy, median OS and PFS were 13 (range 8.0-20.0) and 6 (range 5.0-11.0) months, respectively. Eleven (19.3%) patients experienced grade 3 toxicity, and four patients (7.0%) experienced grade 4 toxicity. CONCLUSION: The efficacy of sunitinib as first- and second-line TKI therapy in a large cohort of patients treated for progressive RAIR TC is herein reported. Further prospective studies are needed to evaluate the effectiveness of sunitinib in RAIR TC. PMID- 27370406 TI - First evidence of established populations of the taiga tick Ixodes persulcatus (Acari: Ixodidae) in Sweden. AB - BACKGROUND: The tick species Ixodes ricinus and I. persulcatus are of exceptional medical importance in the western and eastern parts, respectively, of the Palaearctic region. In Russia and Finland the range of I. persulcatus has recently increased. In Finland the first records of I. persulcatus are from 2004. The apparent expansion of its range in Finland prompted us to investigate if I. persulcatus also occurs in Sweden. METHODS: Dog owners and hunters in the coastal areas of northern Sweden provided information about localities where ticks could be present. In May-August 2015 we used the cloth-dragging method in 36 localities potentially harbouring ticks in the Bothnian Bay area, province Norrbotten (NB) of northern Sweden. Further to the south in the provinces Vasterbotten (VB) and Uppland (UP) eight localities were similarly investigated. RESULTS: Ixodes persulcatus was detected in 9 of 36 field localities in the Bothnian Bay area. Nymphs, adult males and adult females (n = 46 ticks) of I. persulcatus were present mainly in Alnus incana - Sorbus aucuparia - Picea abies - Pinus sylvestris vegetation communities on islands in the Bothnian Bay. Some of these I. persulcatus populations seem to be the most northerly populations so far recorded of this species. Dog owners asserted that their dogs became tick infested on these islands for the first time 7-8 years ago. Moose (Alces alces), hares (Lepus timidus), domestic dogs (Canis lupus familiaris) and ground-feeding birds are the most likely carriers dispersing I. persulcatus in this area. All ticks (n = 124) from the more southern provinces of VB and UP were identified as I. ricinus. CONCLUSIONS: The geographical range of the taiga tick has recently expanded into northern Sweden. Increased information about prophylactic, anti tick measures should be directed to people living in or visiting the coastal areas and islands of the Baltic Bay. PMID- 27370405 TI - Administration of anticonvulsive rescue medication in children-discrepancies between parents' self-reports and limited practical performance. AB - Quality of parents' performance in administering anticonvulsive rescue medication to their children suffering from seizures is unknown. After obtaining ethical approval, we used a questionnaire to ask parents of children with seizures, who had been prescribed rescue medications, about their experience in administering those. To assess the frequency of actually committed drug-handling errors, we let them administer rescue medications to dummy dolls. An expert panel rated the clinical risk of handling errors from "1" (lowest) to "6" (highest). Eighty-one parents completed the study. In the questionnaire, 85 % (100 %) of parents that already conducted rectal (buccal) administration reported that they had never experienced problems. The number of rectal administrations with at least one handling error (97 %, 58/60) was higher than in buccal administration (58 %; 14/24; p < 0.001). According to logistic regressions, previous use of rescue medication was not a predictor of the number of committed errors per process (n. s.). All errors were rated with a high clinical risk (class 4-6). CONCLUSION: By observing parents' administration of rescue medication to dummy dolls, we found a high frequency of clinically relevant drug-handling errors. Most parents, however, self-reported to have never experienced problems while administering rescue medications to their children. WHAT IS KNOWN: * For seizures with duration of more than 5 min, the administration of anticonvulsive rescue medication is recommended. * Outside the hospital, the administration of rescue medication to children is performed most frequently by their parents. What is New: * Most of the parents reported that they had never experienced problems in handling anticonvulsive rescue medication. * But in the observed drug-handling performances, identified errors committed by parents were alarmingly frequent and pose a high clinical risk according to an expert panel. PMID- 27370407 TI - Frailty and sarcopenia as the basis for the phenotypic manifestation of chronic diseases in older adults. AB - Frailty is a functional status that precedes disability and is characterized by decreased functional reserve and increased vulnerability. In addition to disability, the frailty phenotype predicts falls, institutionalization, hospitalization and mortality. Frailty is the consequence of the interaction between the aging process and some chronic diseases and conditions that compromise functional systems and finally produce sarcopenia. Many of the clinical manifestations of frailty are explained by sarcopenia which is closely related to poor physical performance. Reduced regenerative capacity, malperfusion, oxidative stress, mitochondrial dysfunction and inflammation compose the sarcopenic skeletal muscle alterations associated to the frailty phenotype. Inflammation appears as a common determinant for chronic diseases, sarcopenia and frailty. The strategies to prevent the frailty phenotype include an adequate amount of physical activity and exercise as well as pharmacological interventions such as myostatin inhibitors and specific androgen receptor modulators. Cell response to stress pathways such as Nrf2, sirtuins and klotho could be considered as future therapeutic interventions for the management of frailty phenotype and aging-related chronic diseases. PMID- 27370408 TI - Abnormalities in biomarkers of mineral and bone metabolism in kidney donors. AB - Previous studies have suggested that kidney donors may have abnormalities of mineral and bone metabolism typically seen in chronic kidney disease. This may have important implications for the skeletal health of living kidney donors and for our understanding of the pathogenesis of long-term mineral and bone disorders in chronic kidney disease. In this prospective study, 182 of 203 kidney donors and 173 of 201 paired normal controls had markers of mineral and bone metabolism measured before and at 6 and 36 months after donation (ALTOLD Study). Donors had significantly higher serum concentrations of intact parathyroid hormone (24.6% and 19.5%) and fibroblast growth factor-23 (9.5% and 8.4%) at 6 and 36 months, respectively, as compared to healthy controls, and significantly reduced tubular phosphate reabsorption (-7.0% and -5.0%) and serum phosphate concentrations ( 6.4% and -2.3%). Serum 1,25-dihydroxyvitamin D3 concentrations were significantly lower (-17.1% and -12.6%), while 25-hydroxyvitamin D (21.4% and 19.4%) concentrations were significantly higher in donors compared to controls. Moreover, significantly higher concentrations of the bone resorption markers, carboxyterminal cross-linking telopeptide of bone collagen (30.1% and 13.8%) and aminoterminal cross-linking telopeptide of bone collagen (14.2% and 13.0%), and the bone formation markers, osteocalcin (26.3% and 2.7%) and procollagen type I N terminal propeptide (24.3% and 8.9%), were observed in donors. Thus, kidney donation alters serum markers of bone metabolism that could reflect impaired bone health. Additional long-term studies that include assessment of skeletal architecture and integrity are warranted in kidney donors. PMID- 27370409 TI - Fibroblast growth factor 23 and markers of mineral metabolism in individuals with preserved renal function. AB - Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphate homeostasis. Circulating FGF23 is elevated in chronic kidney disease (CKD) and independently associated with poor renal and cardiovascular outcomes and mortality. Because the study of FGF23 in individuals with normal renal function has received little attention, we examined in a large, population-based study of 1128 participants the associations of FGF23 with markers of mineral metabolism and renal function. The median estimated glomerular filtration rate (eGFR) of the cohort was 105 ml/min per 1.73 m(2), and the median plasma FGF23 was 78.5 RU/ml. FGF23 increased and plasma 1,25-dihydroxyvitamin D3 decreased significantly below an eGFR threshold of 102 and 99 ml/min per 1.73 m(2), respectively. In contrast, plasma parathyroid hormone increased continuously with decreasing eGFR and was first significantly elevated at an eGFR of 126 ml/min per 1.73 m(2). On multivariable analysis adjusting for sex, age, body mass index, and GFR, FGF23 was negatively associated with 1,25-dihydroxyvitamin D3, and urinary absolute and fractional calcium excretion but not with serum calcium or parathyroid hormone. We found a positive association of FGF23 with plasma phosphate, but no association with urinary absolute or fractional phosphate excretion and, unexpectedly, a positive association with tubular maximum phosphate reabsorption/GFR. Thus, in the absence of CKD, parathyroid hormone increases earlier than FGF23 when the eGFR decreases. The increase in FGF23 occurs at a higher eGFR threshold than previously reported and is closely associated with a decrease in 1,25-dihydroxyvitamin D3. We speculate that the main demonstrable effect of FGF23 in the setting of preserved renal function is suppression of 1,25-dihydroxyvitamin D3 rather than stimulation of renal phosphate excretion. PMID- 27370410 TI - The complement factor 5a receptor 1 has a pathogenic role in chronic inflammation and renal fibrosis in a murine model of chronic pyelonephritis. AB - Complement factor 5a (C5a) interaction with its receptor (C5aR1) contributes to the pathogenesis of inflammatory diseases, including acute kidney injury. However, its role in chronic inflammation, particularly in pathogen-associated disorders, is largely unknown. Here we tested whether the development of chronic inflammation and renal fibrosis is dependent on C5aR1 in a murine model of chronic pyelonephritis. C5aR1-deficient (C5aR1-/-) mice showed a significant reduction in bacterial load, tubule injury and tubulointerstitial fibrosis in the kidneys following infection, compared with C5aR1-sufficient mice. This was associated with reduced renal leukocyte infiltration specifically for the population of Ly6Chi proinflammatory monocytes/macrophages and reduced intrarenal gene expression of key proinflammatory and profibrogenic factors in C5aR1-/- mice following infection. Antagonizing C5aR1 decreased renal bacterial load, tissue inflammation and tubulointerstitial fibrosis. Ex vivo and in vitro studies showed that under infection conditions, C5a/C5aR1 interaction upregulated the production of proinflammatory and profibrogenic factors by renal tubular epithelial cells and monocytes/macrophages, whereas the phagocytic function of monocytes/macrophages was down-regulated. Thus, C5aR1-dependent bacterial colonization of the tubular epithelium, C5a/C5aR1-mediated upregulation of local inflammatory responses to uropathogenic E. coli and impairment of phagocytic function of phagocytes contribute to persistent bacterial colonization of the kidney, chronic renal inflammation and subsequent tubulointerstitial fibrosis. PMID- 27370411 TI - Fine needle aspiration cytology of a nodal low-grade serous neoplasm: a case report of low-grade serous carcinoma arising from a serous borderline tumour with cyto-histological correlation. PMID- 27370413 TI - Editor's Highlight: Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS): A Web-Based Tool for Addressing the Challenges of Cross-Species Extrapolation of Chemical Toxicity. AB - Conservation of a molecular target across species can be used as a line-of evidence to predict the likelihood of chemical susceptibility. The web-based Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS; https://seqapass.epa.gov/seqapass/) application was developed to simplify, streamline, and quantitatively assess protein sequence/structural similarity across taxonomic groups as a means to predict relative intrinsic susceptibility. The intent of the tool is to allow for evaluation of any potential protein target while remaining amenable to variable degrees of protein characterization, in the context of available information about the chemical/protein interaction and the molecular target itself. To accommodate this flexibility in the analysis, 3 levels of evaluation were developed. The first level of the SeqAPASS analysis compares primary amino acid sequences to a query sequence, calculating a metric for sequence similarity (including detection of orthologs); the second level evaluates sequence similarity within selected functional domains (eg, ligand binding domain); and the third level of analysis compares individual amino acid residue positions of importance for protein conformation and/or interaction with the chemical upon binding. Each level of the SeqAPASS analysis provides additional evidence to apply toward rapid, screening-level assessments of probable cross species susceptibility. Such analyses can support prioritization of chemicals for further evaluation, selection of appropriate species for testing, extrapolation of empirical toxicity data, and/or assessment of the cross species relevance of adverse outcome pathways. Three case studies are described herein to demonstrate application of the SeqAPASS tool: the first 2 focused on predictions of pollinator susceptibility to molt-accelerating compounds and neonicotinoid insecticides, and the third on evaluation of cross-species susceptibility to strobilurin fungicides. These analyses illustrate challenges in species extrapolation and demonstrate the broad utility of SeqAPASS for risk based decision making and research. PMID- 27370414 TI - From the Cover: Zinc Deficiency Worsens and Supplementation Prevents High-Fat Diet Induced Vascular Inflammation, Oxidative Stress, and Pathological Remodeling. AB - Obesity has become a common public health problem in the world and raises the risk of various cardiovascular diseases. Zinc is essential for multiple organs in terms of normal structure and function. The present study investigated the effects of high fat diet (HFD) induced obesity on the aorta in mice, and evaluated whether it can be affected by zinc deficiency or supplementation. Four week-old male C57BL/6J mice were fed HFD with varied amounts of zinc (deficiency, adequate and supplementation) for 3 and 6 months. Results showed that HFD feeding induced a time-dependent aortic remodeling, demonstrated by increased vessel wall thickness, tunica cell proliferation and fibrotic responses, and inflammatory response, reflected by increased expression of inflammatory cytokines (tumor necrosis factor-alpha and vascular cell adhesion molecule 1). HFD feeding also caused aortic oxidative damage, reflected by 3-nitrotyrosine and 4-hydroxy-2 nonenal accumulation, and down-regulated nuclear factor (erythroid-derived 2) like 2 (Nrf2) expression and function, shown by down-regulation of its downstream antioxidants, catalase, NAD(P)H dehydrogenase (quinone 1), and metallothionein expression. The vascular effects of obesity-induced by HFD was exacerbated by zinc deficiency but significantly improved by zinc supplementation. In addition, down-regulation of Nrf2 function and associated antioxidants expression were also worsened by zinc deficiency but improved by zinc supplementation. These results suggest that HFD induces aortic remodeling, which can be exacerbated by zinc deficiency and improved by zinc supplementation. PMID- 27370412 TI - Editor's Highlight: Transplacental and Lactational Transfer of Firemaster(r) 550 Components in Dosed Wistar Rats. AB - Firemaster(r) 550 (FM 550) is a commercial mixture of organophosphate and brominated flame retardants currently in use as a replacement for pentaBDE. Its organophosphate components include triphenyl phosphate (TPHP) and a suite of isopropylated triarylphosphate isomers (ITPs); its brominated components include 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis (2-ethylhexyl)-2,3,4,5 tetrabromophthalate (BEH-TEBP). Taken together, these chemicals have been shown to be endocrine disrupting and potentially toxic, and human exposure to them is widespread. In this study, maternal transfer of FM 550 components, and in some cases their metabolites, was investigated in dosed Wistar rats. Gestational and lactational transfer were examined separately, with dams orally exposed to 300 or 1000 ug of FM 550 for 10 consecutive days during gestation (gestational day [GD] 9-18) or lactation (postnatal day [PND] 3-12). Levels of parent compounds were measured in fetus and whole pup tissue homogenates, and in dam and pup serum, and several metabolites were measured in dam and pup urine. EH-TBB body burdens resulting from lactational transfer were approximately 200- to 300-fold higher than those resulting from placental transfer, whereas low levels of BEH-TEBP were transferred during both lactation and gestation. TPHP and ITPs were rapidly metabolized by the dams and were not detected in whole tissue homogenates. However, diphenyl phosphate (DPHP) and mono-isopropylphenyl phenyl phosphate (ip PPP) were detected in urine from the dosed animals. This study is the first to confirm ip-PPP as a urinary metabolite of ITPs and establish a pharmacokinetic profile of FM 550 in a mammalian model. KEY WORDS: Firemaster 550 ;: lactational transfer ;: gestational transfer; metabolites; rodent. PMID- 27370418 TI - Invited Article: A precise instrument to determine the Planck constant, and the future kilogram. AB - A precise instrument, called a watt balance, compares mechanical power measured in terms of the meter, the second, and the kilogram to electrical power measured in terms of the volt and the ohm. A direct link between mechanical action and the Planck constant is established by the practical realization of the electrical units derived from the Josephson and the quantum Hall effects. We describe in this paper the fourth-generation watt balance at the National Institute of Standards and Technology (NIST), and report our initial determination of the Planck constant obtained from data taken in late 2015 and the beginning of 2016. A comprehensive analysis of the data and the associated uncertainties led to the SI value of the Planck constant, h = 6.626 069 83(22) * 10(-34) J s. The relative standard uncertainty associated with this result is 34 * 10(-9). PMID- 27370419 TI - Contributed Review: Experimental characterization of inverse piezoelectric strain in GaN HEMTs via micro-Raman spectroscopy. AB - Micro-Raman thermography is one of the most popular techniques for measuring local temperature rise in gallium nitride (GaN) high electron mobility transistors with high spatial and temporal resolution. However, accurate temperature measurements based on changes in the Stokes peak positions of the GaN epitaxial layers require properly accounting for the stress and/or strain induced by the inverse piezoelectric effect. It is common practice to use the pinched OFF state as the unpowered reference for temperature measurements because the vertical electric field in the GaN buffer that induces inverse piezoelectric stress/strain is relatively independent of the gate bias. Although this approach has yielded temperature measurements that agree with those derived from the Stokes/anti-Stokes ratio and thermal models, there has been significant difficulty in quantifying the mechanical state of the GaN buffer in the pinched OFF state from changes in the Raman spectra. In this paper, we review the experimental technique of micro-Raman thermography and derive expressions for the detailed dependence of the Raman peak positions on strain, stress, and electric field components in wurtzite GaN. We also use a combination of semiconductor device modeling and electro-mechanical modeling to predict the stress and strain induced by the inverse piezoelectric effect. Based on the insights gained from our electro-mechanical model and the best values of material properties in the literature, we analyze changes in the E2 high and A1 (LO) Raman peaks and demonstrate that there are major quantitative discrepancies between measured and modeled values of inverse piezoelectric stress and strain. We examine many of the hypotheses offered in the literature for these discrepancies but conclude that none of them satisfactorily resolves these discrepancies. Further research is needed to determine whether the electric field components could be affecting the phonon frequencies apart from the inverse piezoelectric effect in wurtzite GaN, which has been predicted theoretically in zinc blende gallium arsenide (GaAs). PMID- 27370416 TI - Editor's Highlight: Subvisible Aggregates of Immunogenic Proteins Promote a Th1 Type Response. AB - Protein aggregation is associated with enhanced immunogenicity of biotherapeutics. As a result, regulatory guidelines recommend screening for aggregation during bioprocessing. However, the mechanisms underlying the enhanced immunogenicity of aggregates are poorly understood. In the investigations described herein, the immunogenicity in mice of a humanized single chain variable antibody fragment (scFv) purified after expression in Escherichia coli has been examined. Reproducible scFv aggregates were obtained within the subvisible particle size range (mean diameter 2 um) using thermal and mechanical stresses. Intraperitoneal immunization of BALB/c strain mice with 1 mg/ml of aggregated or monomeric scFv induced similar IgG and IgG1 antibody responses. In contrast, aggregate preparations stimulated significantly higher levels of anti-scFv IgG2a antibody than did the monomer. In comparative studies, aggregates of ovalbumin (OVA) within the subvisible particle size range were prepared by stir stress, and their immunogenicity compared with that of monomeric OVA in mice. Aggregated and monomeric OVA induced similar anti-OVA IgG and IgG1 antibody responses, whereas IgG2a antibody levels were significantly higher in aggregate-immunized mice. Furthermore, cytokine profiles in supernatants taken from splenocyte-dendritic cell co-cultures were consistent with aggregated preparations inducing a T helper (Th) 1-type response. Aggregated proteins within the subvisible range were therefore shown to induce a preferential Th1 type response, whereas monomeric proteins elicited a selective Th2 response. These data indicate that protein aggregation can impact on both the vigor and quality of immune responses. PMID- 27370420 TI - A three-layer magnetic shielding for the MAIUS-1 mission on a sounding rocket. AB - Bose-Einstein-Condensates (BECs) can be used as a very sensitive tool for experiments on fundamental questions in physics like testing the equivalence principle using matter wave interferometry. Since the sensitivity of these experiments in ground-based environments is limited by the available free fall time, the QUANTUS project started to perform BEC interferometry experiments in micro-gravity. After successful campaigns in the drop tower, the next step is a space-borne experiment. The MAIUS-mission will be an atom-optical experiment that will show the feasibility of experiments with ultra-cold quantum gases in microgravity in a sounding rocket. The experiment will create a BEC of 10(5) (87)Rb-atoms in less than 5 s and will demonstrate application of basic atom interferometer techniques over a flight time of 6 min. The hardware is specifically designed to match the requirements of a sounding rocket mission. Special attention is thereby spent on the appropriate magnetic shielding from varying magnetic fields during the rocket flight, since the experiment procedures are very sensitive to external magnetic fields. A three-layer magnetic shielding provides a high shielding effectiveness factor of at least 1000 for an undisturbed operation of the experiment. The design of this magnetic shielding, the magnetic properties, simulations, and tests of its suitability for a sounding rocket flight are presented in this article. PMID- 27370415 TI - Association Between Variants in Arsenic (+3 Oxidation State) Methyltranserase (AS3MT) and Urinary Metabolites of Inorganic Arsenic: Role of Exposure Level. AB - Variants in AS3MT, the gene encoding arsenic (+3 oxidation state) methyltranserase, have been shown to influence patterns of inorganic arsenic (iAs) metabolism. Several studies have suggested that capacity to metabolize iAs may vary depending on levels of iAs exposure. However, it is not known whether the influence of variants in AS3MT on iAs metabolism also vary by level of exposure. We investigated, in a population of Mexican adults exposed to drinking water As, whether associations between 7 candidate variants in AS3MT and urinary iAs metabolites were consistent with prior studies, and whether these associations varied depending on the level of exposure. Overall, associations between urinary iAs metabolites and AS3MT variants were consistent with the literature. Referent genotypes, defined as the genotype previously associated with a higher percentage of urinary dimethylated As (DMAs%), were associated with significant increases in the DMAs% and ratio of DMAs to monomethylated As (MAs), and significant reductions in MAs% and iAs%. For 3 variants, associations between genotypes and iAs metabolism were significantly stronger among subjects exposed to water As >50 versus <=50 ppb (water As X genotype interaction P < .05). In contrast, for 1 variant (rs17881215), associations were significantly stronger at exposures <=50 ppb. Results suggest that iAs exposure may influence the extent to which several AS3MT variants affect iAs metabolism. The variants most strongly associated with iAs metabolism-and perhaps with susceptibility to iAs-associated disease-may vary in settings with exposure level. PMID- 27370421 TI - A scanning drift tube apparatus for spatiotemporal mapping of electron swarms. AB - A "scanning" drift tube apparatus, capable of mapping of the spatiotemporal evolution of electron swarms, developing between two plane electrodes under the effect of a homogeneous electric field, is presented. The electron swarms are initiated by photoelectron pulses and the temporal distributions of the electron flux are recorded while the electrode gap length (at a fixed electric field strength) is varied. Operation of the system is tested and verified with argon gas; the measured data are used for the evaluation of the electron bulk drift velocity. The experimental results for the space-time maps of the electron swarms - presented here for the first time - also allow clear observation of deviations from hydrodynamic transport. The swarm maps are also reproduced by particle simulations. PMID- 27370423 TI - Optomechanical design and construction of a vacuum-compatible optical parametric oscillator for generation of squeezed light. AB - With the recent detection of gravitational waves, non-classical light sources are likely to become an essential element of future detectors engaged in gravitational wave astronomy and cosmology. Operating a squeezed light source under high vacuum has the advantages of reducing optical losses and phase noise compared to techniques where the squeezed light is introduced from outside the vacuum. This will ultimately provide enhanced sensitivity for modern interferometric gravitational wave detectors that will soon become limited by quantum noise across much of the detection bandwidth. Here we describe the optomechanical design choices and construction techniques of a near monolithic glass optical parametric oscillator that has been operated under a vacuum of 10( 6) mbar. The optical parametric oscillator described here has been shown to produce 8.6 dB of quadrature squeezed light in the audio frequency band down to 10 Hz. This performance has been maintained for periods of around an hour and the system has been under vacuum continuously for several months without a degradation of this performance. PMID- 27370422 TI - Measuring the diffraction properties of an imaging quartz(211) crystal. AB - A dual goniometer X-ray system was used to measure the reflectivity curve for a spherically bent quartz(211) crystal. An analysis of the dual goniometer instrument response function for the rocking curve width measurement was developed and tested against the actual measurements. The rocking curve was measured at 4510.8 eV using the Ti Kalpha1 characteristic spectral line. The crystal is the dispersion element for a high resolution spectrometer used for plasma studies. It was expected to have a very narrow rocking curve width. The analysis showed that we could measure the upper bound for the rocking curve width of the Qz(211) crystal. The upper bound was 58 MUrad giving a lower bound for the instrument resolving power E/DeltaE = 34 000. Greatly improved insight into the dual goniometer operation and its limitations was achieved. PMID- 27370424 TI - Fast phase stabilization of a low frequency beat note for atom interferometry. AB - Atom interferometry experiments rely on the ability to obtain a stable signal that corresponds to an atomic phase. For interferometers that use laser beams to manipulate the atoms, noise in the lasers can lead to errors in the atomic measurement. In particular, it is often necessary to actively stabilize the optical phase between two frequency components of the beams. Typically this is achieved using a time-domain measurement of a beat note between the two frequencies. This becomes challenging when the frequency difference is small and the phase measurement must be made quickly. The method presented here instead uses a spatial interference detection to rapidly measure the optical phase for arbitrary frequency differences. A feedback system operating at a bandwidth of about 10 MHz could then correct the phase in about 3 MUs. This time is short enough that the phase correction could be applied at the start of a laser pulse without appreciably degrading the fidelity of the atom interferometer operation. The phase stabilization system was demonstrated in a simple atom interferometer measurement of the (87)Rb recoil frequency. PMID- 27370425 TI - High intensity vacuum ultraviolet and extreme ultraviolet production by noncollinear mixing in laser vaporized media. AB - A method is described for generating intense pulsed vacuum ultraviolet (VUV) and extreme ultraviolet (XUV) laser radiation by resonance enhanced four-wave mixing of commercial pulsed nanosecond lasers in laser vaporized mercury under windowless conditions. By employing noncollinear mixing of the input beams, the need of dispersive elements such as gratings for separating the VUV/XUV from the residual UV and visible beams is eliminated. A number of schemes are described, facilitating access to the 9.9-14.6 eV range. A simple and convenient scheme for generating wavelengths of 125 nm, 112 nm, and 104 nm (10 eV, 11 eV, and 12 eV) using two dye lasers without the need for dye changes is described. PMID- 27370426 TI - Dichroic atomic vapor laser lock with multi-gigahertz stabilization range. AB - A dichroic atomic vapor laser lock (DAVLL) system exploiting buffer-gas-filled millimeter-scale vapor cells is presented. This system offers similar stability as achievable with conventional DAVLL system using bulk vapor cells, but has several important advantages. In addition to its compactness, it may provide continuous stabilization in a multi-gigahertz range around the optical transition. This range may be controlled either by changing the temperature of the vapor or by application of a buffer gas under an appropriate pressure. In particular, we experimentally demonstrate the ability of the system to lock the laser frequency between two hyperfine components of the (85)Rb ground state or as far as 16 GHz away from the closest optical transition. PMID- 27370427 TI - Hybrid PSO-ASVR-based method for data fitting in the calibration of infrared radiometer. AB - The present paper describes a hybrid particle swarm optimization-adaptive support vector regression (PSO-ASVR)-based method for data fitting in the calibration of infrared radiometer. The proposed hybrid PSO-ASVR-based method is based on PSO in combination with Adaptive Processing and Support Vector Regression (SVR). The optimization technique involves setting parameters in the ASVR fitting procedure, which significantly improves the fitting accuracy. However, its use in the calibration of infrared radiometer has not yet been widely explored. Bearing this in mind, the PSO-ASVR-based method, which is based on the statistical learning theory, is successfully used here to get the relationship between the radiation of a standard source and the response of an infrared radiometer. Main advantages of this method are the flexible adjustment mechanism in data processing and the optimization mechanism in a kernel parameter setting of SVR. Numerical examples and applications to the calibration of infrared radiometer are performed to verify the performance of PSO-ASVR-based method compared to conventional data fitting methods. PMID- 27370428 TI - Active stabilization of a diode laser injection lock. AB - We report on a device to electronically stabilize the optical injection lock of a semiconductor diode laser. Our technique uses as discriminator the peak height of the laser's transmission signal on a scanning Fabry-Perot cavity and feeds back to the diode current, thereby maintaining maximum optical power in the injected mode. A two-component feedback algorithm provides constant optimization of the injection lock, keeping it robust to slow thermal drifts and allowing fast recovery from sudden failures such as temporary occlusion of the injection beam. We demonstrate the successful performance of our stabilization method in a diode laser setup at 399 nm used for laser cooling of Yb atoms. The device eases the requirements on passive stabilization and can benefit any diode laser injection lock application, particularly those where several such locks are employed. PMID- 27370429 TI - Time resolved 3D momentum imaging of ultrafast dynamics by coherent VUV-XUV radiation. AB - We present a new experimental setup for measuring ultrafast nuclear and electron dynamics of molecules after photo-excitation and ionization. We combine a high flux femtosecond vacuum ultraviolet (VUV) and extreme ultraviolet (XUV) source with an internally cold molecular beam and a 3D momentum imaging particle spectrometer to measure electrons and ions in coincidence. We describe a variety of tools developed to perform pump-probe studies in the VUV-XUV spectrum and to modify and characterize the photon beam. First benchmark experiments are presented to demonstrate the capabilities of the system. PMID- 27370430 TI - Mid-infrared concentration-modulated noise-immune cavity-enhanced optical heterodyne molecular spectroscopy of a continuous supersonic expansion discharge source. AB - Concentration-modulated noise-immune cavity-enhanced optical heterodyne molecular spectroscopy (NICE-OHMS) is implemented for the first time on a continuous gas flow pinhole supersonic expansion discharge source for the study of cooled molecular ions. The instrument utilizes a continuous-wave optical parametric oscillator easily tunable from 2.5 to 3.9 MUm and demonstrates a noise equivalent absorption of ~1 * 10(-9) cm(-1). The effectiveness of concentration-modulated NICE-OHMS is tested through the acquisition of transitions in the nu1 fundamental band of HN2 (+) centered near 3234 cm(-1), with a signal-to-noise of ~40 obtained for the strongest transitions. The technique is used to characterize the cooling abilities of the supersonic expansion discharge source itself, and a Boltzmann analysis determines a rotational temperature of ~29 K for low rotational states of HN2 (+). Further improvements are discussed that will enable concentration modulated NICE-OHMS to reach its full potential for the detection of molecular ions formed in supersonic expansion discharges. PMID- 27370431 TI - An enhanced Cramer-Rao bound weighted method for attitude accuracy improvement of a star tracker. AB - This study presents a non-average weighted method for the QUEST (QUaternion ESTimator) algorithm, using the inverse value of root sum square of Cramer-Rao bound and focal length drift errors of the tracking star as weight, to enhance the pointing accuracy of a star tracker. In this technique, the stars that are brighter, or at low angular rate, or located towards the center of star field will be given a higher weight in the attitude determination process, and thus, the accuracy is readily improved. Simulations and ground test results demonstrate that, compared to the average weighted method, it can reduce the attitude uncertainty by 10%-20%, which is confirmed particularly for the sky zones with non-uniform distribution of stars. Moreover, by using the iteratively weighted center of gravity algorithm as the newly centroiding method for the QUEST algorithm, the current attitude uncertainty can be further reduced to 44% with a negligible additional computing load. PMID- 27370432 TI - New ultrarapid-scanning interferometer for FT-IR spectroscopy with microsecond time-resolution. AB - A novel Fourier-transform infrared (FT-IR) rapid-scan spectrometer has been developed (patent pending EP14194520.4) which yields 1000 times higher time resolution as compared to conventional rapid-scanning spectrometers. The central element to achieve faster scanning rates is based on a sonotrode whose front face represents the movable mirror of the interferometer. A prototype spectrometer with a time resolution of 13 MUs was realized, capable of fully automated long term measurements with a flow cell for liquid samples, here a photosynthetic membrane protein in solution. The performance of this novel spectrometer is demonstrated by recording the photoreaction of bacteriorhodopsin initiated by a short laser pulse that is synchronized to the data recording. The resulting data are critically compared to those obtained by step-scan spectroscopy and demonstrate the relevance of performing experiments on proteins in solution. The spectrometer allows for future investigations of fast, non-repetitive processes, whose investigation is challenging to step-scan FT-IR spectroscopy. PMID- 27370433 TI - Double nanosecond pulses generation in ytterbium fiber laser. AB - Double pulse generation mode for nanosecond ytterbium fiber laser was developed. Two sequential 60-200 ns laser pulses with variable delay between them were generated by acousto-optic modulator opening with continuous diode pumping. A custom radio frequency generator was developed to produce two sequential "opening" radio pulses with a delay of 0.2-1 MUs. It was demonstrated that double pulse generation did not decrease the average laser power while providing the control over the laser pulse power profile. Surprisingly, a greater peak power in the double pulse mode was observed for the second laser pulse. Laser crater studies and plasma emission measurements revealed an improved efficiency of laser ablation in the double pulse mode. PMID- 27370435 TI - Characterization and optimization of illumination vector for contouring surface form and feature using DSPI. AB - Surface defect or damage is one of the critical factors leading to the failure of engineering materials and structures. The methodologies for the measurement of surface shape and feature or defect have been extensively explored and developed over the past few decades, including both contact and non-contact methods. Speckle pattern interferometry, as a non-contact optical method, has been demonstrated to effectively contour the surface shape through adjusting the illumination vector. However, few studies have been made to investigate the effect of the initial position of the illumination source as well as the source translation direction. In this paper, we report to carry out a study of measuring the surface form and feature using digital speckle pattern interferometry system via a slight translation of illumination source. Through theoretically analyzing the sensitivity factor along with the experimental validation, it is shown that the contouring fringe is more sensitive to the surface height with an off-axis illumination than the paraxial illumination. It is also found that translating the source along axial and lateral direction can be both used for the surface shape re-construction. PMID- 27370434 TI - The cryogenic storage ring CSR. AB - An electrostatic cryogenic storage ring, CSR, for beams of anions and cations with up to 300 keV kinetic energy per unit charge has been designed, constructed, and put into operation. With a circumference of 35 m, the ion-beam vacuum chambers and all beam optics are in a cryostat and cooled by a closed-cycle liquid helium system. At temperatures as low as (5.5 +/- 1) K inside the ring, storage time constants of several minutes up to almost an hour were observed for atomic and molecular, anion and cation beams at an energy of 60 keV. The ion-beam intensity, energy-dependent closed-orbit shifts (dispersion), and the focusing properties of the machine were studied by a system of capacitive pickups. The Schottky-noise spectrum of the stored ions revealed a broadening of the momentum distribution on a time scale of 1000 s. Photodetachment of stored anions was used in the beam lifetime measurements. The detachment rate by anion collisions with residual-gas molecules was found to be extremely low. A residual-gas density below 140 cm(-3) is derived, equivalent to a room-temperature pressure below 10( 14) mbar. Fast atomic, molecular, and cluster ion beams stored for long periods of time in a cryogenic environment will allow experiments on collision- and radiation-induced fragmentation processes of ions in known internal quantum states with merged and crossed photon and particle beams. PMID- 27370436 TI - A rapid excitation-emission matrix fluorometer utilizing supercontinuum white light and acousto-optic tunable filters. AB - Scanning speed and coupling efficiency of excitation light to optic fibres are two major technical challenges that limit the potential of fluorescence excitation-emission matrix (EEM) spectrometer for on-line applications and in vivo studies. In this paper, a novel EEM system, utilizing a supercontinuum white light source and acousto-optic tunable filters (AOTFs), was introduced and evaluated. The supercontinuum white light, generated by pumping a nonlinear photonic crystal fiber with an 800 nm femtosecond laser, was efficiently coupled into a bifurcated optic fiber bundle. High speed EEM spectral scanning was achieved using AOTFs both for selecting excitation wavelength and scanning emission spectra. Using calibration lamps (neon and mercury argon), wavelength deviations were determined to vary from 0.18 nm to -0.70 nm within the spectral range of 500-850 nm. Spectral bandwidth for filtered excitation light broadened by twofold compared to that measured with monochromatic light between 650 nm and 750 nm. The EEM spectra for methanol solutions of laser dyes were successfully acquired with this rapid fluorometer using an integration time of 5 s. PMID- 27370437 TI - Development of speckle-free channel-cut crystal optics using plasma chemical vaporization machining for coherent x-ray applications. AB - We have developed a method of fabricating speckle-free channel-cut crystal optics with plasma chemical vaporization machining, an etching method using atmospheric pressure plasma, for coherent X-ray applications. We investigated the etching characteristics to silicon crystals and achieved a small surface roughness of less than 1 nm rms at a removal depth of >10 MUm, which satisfies the requirements for eliminating subsurface damage while suppressing diffuse scattering from rough surfaces. We applied this method for fabricating channel cut Si(220) crystals for a hard X-ray split-and-delay optical system and confirmed that the crystals provided speckle-free reflection profiles under coherent X-ray illumination. PMID- 27370438 TI - Improved mid infrared detector for high spectral or spatial resolution and synchrotron radiation use. AB - When using bright, small effective size sources, such as synchrotron radiation light beam, for broadband spectroscopy at spectral or spatial high resolution for mid-IR FTIR measurements, a marked detectivity improvement can be achieved by setting up a device matching the detector optical etendue to that of the source. Further improvement can be achieved by reducing the background unmodulated flux and other intrinsic noise sources using a lower temperature cryogen, such as liquid helium. By the combined use of cooled apertures, cold reimaging optics, filters and adapted detector polarization, and preamplification electronics, the sensitivity of a HgCdTe photoconductive IR detector can be improved by a significant factor with respect to standard commercial devices (more than one order of magnitude on average over 6-20 MUm region) and the usable spectral range extended to longer wavelengths. The performances of such an optimized detector developed on the AILES Beamline at SOLEIL are presented here. PMID- 27370439 TI - Simulation of He(+) induced afterpulses in PMTs. AB - We report on a Monte Carlo simulation study of afterpulses due to trace gases in EMI 9235QA photomultipliers that are widely used in many luminescence detection systems operating in single photon counting mode. The numerical simulation takes into account the nonuniform electric field distribution and processes including elastic scattering: e + He -> e + He, excitation: e + He -> e + He(*), ionization: e + He -> 2e + He(+), elastic scattering: He(+) + He -> He(+) + He, charge transfer: He(+) + He -> Hef + He(+) (Hef indicates a fast neutral) and elastic scattering: Hef + He -> Hef + He(f). The simulated and the measured time of flight distributions agree well. In addition, the above simulated processes demonstrate mechanisms of the observed series of pulses brought about by a single helium atom ionization. PMID- 27370440 TI - 1 Hz linewidth Ti:sapphire laser as local oscillator for (40)Ca(+) optical clocks. AB - A Ti:sapphire laser at 729 nm is frequency stabilized to an ultra-stable ultra low thermal expansion coefficient (ULE) cavity by means of Pound-Drever-Hall method. An acousto-optic modulator is used as the fast frequency feedback component. 1 Hz linewidth and 2 * 10(-15) frequency stability at 1-100 s are characterized by optical beating with a separated Fabry-Perot cavity stabilized diode laser. Compared to the universal method that the error signal feedback to inject current of a diode laser, this scheme is demonstrated to be simple and also effective for linewidth narrowing. The temperature of zero coefficient of the thermal expansion of the ULE cavity is measured with the help of a femto second frequency comb. And the performance of the laser is well defined by locking it to the unperturbed clock transition line-center of 4 S1/2-3 D5/2 clock transition of a single laser cooled (40)Ca(+) ion. A Fourier-transform limited resonance of 6 Hz (Deltav/v = 1.5 * 10(-14)) is observed. This laser is also used as the local oscillator for the comparison experiment of two (40)Ca(+) ion optical clocks and improves the stability of comparison for an order of magnitude better than the previous results. PMID- 27370441 TI - Investigation on emission characteristics of metal-ceramic cathode applied to industrial X-ray diode. AB - The industrial x-ray diode with high impedance configuration is usually adopted to generate repetitive x-ray, but its performance would be worsened due to lower electric field on the cathode of diode when a voltage of several hundreds of kV is applied. To improve its performance, a novel metal-ceramic cathode is proposed in this paper. Key factors (width, relative permittivity of ceramic, and so on) affecting electric field distribution on triple points are analyzed by electrostatic field calculation program, so as to optimize the design of this novel cathode. Experiments are done to study the characteristics including emission current of cathode, diode voltage duration, diode mean dynamic impedance, and diode impedance drop velocity within diode power duration. The results show that metal-ceramic cathode could improve diode performance by enhancing emission current and stabling impedance; the impedance drop velocity of diode with spoke-shaped metal-ceramic cathode was reduced to -5 Omega ns(-1) within diode power duration, comparing to -15 Omega ns(-1) with metal foil cathode. PMID- 27370442 TI - Deposition of dielectric films on silicon using a fore-vacuum plasma electron source. AB - We describe an experiment on the use of a fore-vacuum-pressure, plasma-cathode, electron beam source with current up to 100 mA and beam energy up to 15 keV for deposition of Mg and Al oxide films on Si substrates in an oxygen atmosphere at a pressure of 10 Pa. The metals (Al and Mg) were evaporated and ionized using the electron beam with the formation of a gas-metal beam-plasma. The plasma was deposited on the surface of Si substrates. The elemental composition of the deposited films was analyzed. PMID- 27370443 TI - A simple approximation for the current-voltage characteristics of high-power, relativistic diodes. AB - A simple approximation for the current-voltage characteristics of a relativistic electron diode is presented. The approximation is accurate from non-relativistic through relativistic electron energies. Although it is empirically developed, it has many of the fundamental properties of the exact diode solutions. The approximation is simple enough to be remembered and worked on almost any pocket calculator, so it has proven to be quite useful on the laboratory floor. PMID- 27370444 TI - Conceptual moderator studies for the Spallation Neutron Source short-pulse second target station. AB - Candidate moderator configurations for a short-pulse second target station (STS) at the Oak Ridge National Laboratory Spallation Neutron Source (SNS) have been identified using a global optimizer framework built around the MCNPX particle transport code. Neutron brightness metrics were selected as the figure-of-merit. We assumed that STS would use one out of six proton pulses produced by an SNS accelerator upgraded to operate at 1.3 GeV proton energy, 2.8 MW power and 60 Hz repetition rate. The simulations indicate that the peak brightness can be increased by a factor of 5 and 2.5 on a per proton pulse basis compared to the SNS first target station for both coupled and decoupled para-hydrogen moderators, respectively. Additional increases by factors of 3 and 2 were demonstrated for coupled and decoupled moderators, respectively, by reducing the area of neutron emission from 100 * 100 mm(2) to 20 * 20 mm(2). This increase in brightness has the potential to translate to an increase of beam intensity at the instruments' sample positions even though the total neutron emission of the smaller moderator is less than that of the larger. This is especially true for instruments with small samples (beam dimensions). The increased fluxes in the STS moderators come at accelerated poison and de-coupler burnout and higher radiation-induced material damage rates per unit power, which overall translate into lower moderator lifetimes. A first effort was undertaken to group decoupled moderators into a cluster collectively positioning them at the peak neutron production zone in the target and having a three-port neutron emission scheme that complements that of a cylindrical coupled moderator. PMID- 27370445 TI - Alternative uses of a megavolt tandem accelerator for few-keV studies with ion source SIMS monitoring. AB - We increase the versatility of a tandem electrostatic accelerator by implementing simple modifications to the standard operation procedure. While keeping its ability to deliver MeV ion beams, we show that the experimental setup can (i) provide good quality ion beams in the few-keV energy range and (ii) be used to study ion-beam surface modification with simultaneous secondary ion mass spectrometry. This latter task is accomplished without using any chamber connected to the accelerator exit. We perform mass spectrometry of the few-keV anions produced in the ion source by measuring their neutral counterparts at the accelerator exit with energies up to 1.7 MeV. With an additional modification, a high-current few-keV regime is obtained, using the ion source as an irradiation chamber and the accelerator itself only as a mass spectrometer. As an example of application, we prepare a sample for the study of ion-beam assisted dewetting of a thin Au film on a Si substrate. PMID- 27370446 TI - Applicability of micro-channel plate followed by phosphor screen to charged particles. AB - This paper experimentally investigates the applicability of a micro-channel plate (MCP) followed by a phosphor screen to charged particles along with a calibration method for estimating the acceptable limit of input particle flux and appropriate operation parameters of a particular MCP. For the first time, plasmas consisting of only lithium ions are injected into the MCP. Despite large ion numbers (Ni) on the order of ?10(7), no deterioration in the effective gain (alphaG) of the MCP owing to an excess amount of the extracted charge occurs in a certain range of the amplifier voltage (DeltaUM) applied to the MCP. The measured alphaG nearly agrees with the expected value. However, once DeltaUM exceeds a limit value, alphaG eventually begins to saturate. This is also verified in experiments using pure electron plasmas. An appropriate range of DeltaUM is presented to avoid saturation and, finally, derive Ni directly from the secondary electron current outputted from the MCP only after the indispensable calibration. PMID- 27370447 TI - Simple synchronization technique of a mode-locked laser for Laser-Compton scattering gamma-ray source. AB - We propose a simple and effective synchronization technique between a reference electrical oscillator and a mode-locked laser for a narrowband picosecond Laser Compton scattering gamma-ray source by using a commercial-based 1-chip frequency synthesizer, which is widely used in radio communication. The mode-locked laser has been successfully synchronized in time with a jitter of 180 fs RMS for 10 Hz 100 kHz bandwidth. A good stability of 640 MUHz at 80 MHz repetition rate for 10 h operation has also been confirmed. We discuss in detail the design and performance of this technique (in terms of timing jitter, stability, and validity). PMID- 27370448 TI - Lineshape spectroscopy with a very high resolution, very high signal-to-noise crystal spectrometer. AB - We have developed a high-resolution x-ray spectrometer for measuring the shapes of spectral lines produced from laser-irradiated targets on the Orion laser facility. The instrument utilizes a spherically bent crystal geometry to spatially focus and spectrally analyze photons from foil or microdot targets. The high photon collection efficiency resulting from its imaging properties allows the instrument to be mounted outside the Orion chamber, where it is far less sensitive to particles, hard x-rays, or electromagnetic pulses than instruments housed close to the target chamber center in ten-inch manipulators. Moreover, Bragg angles above 50 degrees are possible, which provide greatly improved spectral resolution compared to radially viewing, near grazing-incidence crystal spectrometers. These properties make the new instrument an ideal lineshape diagnostic for determining plasma temperature and density. We describe its calibration on the Livermore electron beam ion trap facility and present spectral data of the K-shell emission from highly charged sulfur produced by long-pulse as well as short-pulse beams on the Orion laser in the United Kingdom. PMID- 27370449 TI - High energy X-ray pinhole imaging at the Z facility. AB - A new high photon energy (hnu > 15 keV) time-integrated pinhole camera (TIPC) has been developed as a diagnostic instrument at the Z facility. This camera employs five pinholes in a linear array for recording five images at once onto an image plate detector. Each pinhole may be independently filtered to yield five different spectral responses. The pinhole array is fabricated from a 1-cm thick tungsten block and is available with either straight pinholes or conical pinholes. Each pinhole within the array block is 250 MUm in diameter. The five pinholes are splayed with respect to each other such that they point to the same location in space, and hence present the same view of the radiation source at the Z facility. The fielding distance from the radiation source is 66 cm and the nominal image magnification is 0.374. Initial experimental results from TIPC are shown to illustrate the performance of the camera. PMID- 27370451 TI - 2-D soft x-ray arrays in the EAST. AB - A high spatial and temporal resolution soft x-ray (SXR) imaging diagnostic has been installed in EAST for the study of magnetohydrodynamics activities and core high-Z impurity transport. Up to 122 lines of sight view the poloidal plasma from three directions (two up-down symmetrical horizontal arrays and one vertical array), which renders the diagnostic able to provide detailed tomographic reconstructions under various conditions. Fourier-Bessel method based on flux coordinates was employed for 2-D SXR tomographic reconstruction. Examples of several events measured by SXR diagnostic in EAST are shown, namely the crash patterns of sawtooth, periodical burst of edge localized modes, and the transport of high-Z intrinsic impurities. PMID- 27370450 TI - Development of the radial neutron camera system for the HL-2A tokamak. AB - A new radial neutron camera system has been developed and operated recently in the HL-2A tokamak to measure the spatial and time resolved 2.5 MeV D-D fusion neutron, enhancing the understanding of the energetic-ion physics. The camera mainly consists of a multichannel collimator, liquid-scintillation detectors, shielding systems, and a data acquisition system. Measurements of the D-D fusion neutrons using the camera have been successfully performed during the 2015 HL-2A experiment campaign. The measurements show that the distribution of the fusion neutrons in the HL-2A plasma has a peaked profile, suggesting that the neutral beam injection beam ions in the plasma have a peaked distribution. It also suggests that the neutrons are primarily produced from beam-target reactions in the plasma core region. The measurement results from the neutron camera are well consistent with the results of both a standard (235)U fission chamber and NUBEAM neutron calculations. In this paper, the new radial neutron camera system on HL 2A and the first experimental results are described. PMID- 27370452 TI - Pulse generator with intermediate inductive storage as a lightning simulator. AB - Compact transportable generators are required for simulating a lightning current pulse for electrical apparatus testing. A bi-exponential current pulse has to be formed by such a generator (with a current rise time of about two orders of magnitude faster than the damping time). The objective of this study was to develop and investigate a compact pulse generator with intermediate inductive storage and a fuse opening switch as a simulator of lightning discharge. A Marx generator (six stages) with a capacitance of 1 MUF and an output voltage of 240 kV was employed as primary storage. In each of the stages, two IK-50/3 (50 kV, 3 MUF) capacitors are connected in parallel. The generator inductance is 2 MUH. A test bed for the investigations was assembled with this generator. The generator operates without SF6 and without oil in atmospheric air, which is very important in practice. Straight copper wires with adjustable lengths and diameters were used for the electro-explosive opening switch. Tests were made with active inductive loads (up to 0.1 Omega and up to 6.3 MUH). The current rise time is lower than 1200 ns, and the damping time can be varied from 35 to 125 MUs, following the definition of standard lightning current pulse in the IEC standard. Moreover, 1D MHD calculations of the fuse explosion were carried out self consistently with the electric circuit equations, in order to calculate more accurately the load pulse parameters. The calculations agree fairly well with the tests. On the basis of the obtained results, the design of a transportable generator was developed for a lightning simulator with current of 50 kA and a pulse shape corresponding to the IEEE standard. PMID- 27370453 TI - A cryogen-free low temperature scanning tunneling microscope capable of inelastic electron tunneling spectroscopy. AB - The design and performance of a cryogen-free low temperature scanning tunneling microscope (STM) housed in ultrahigh vacuum (UHV) are reported. The cryogen-free design was done by directly integrating a Gifford-McMahon cycle cryocooler to a Besocke-type STM, and the vibration isolation was achieved by using a two-stage rubber bellow between the cryocooler and a UHV-STM interface with helium exchange gas cooling. A base temperature of 15 K at the STM was achieved, with a possibility to further decrease by using a cryocooler with higher cooling power and adding additional low temperature stage under the exchange gas interface. Atomically sharp STM images and high resolution dI/dV spectra on various samples were demonstrated. Furthermore, we reported the inelastic tunneling spectroscopy on a single carbon monoxide molecule adsorbed on Ag(110) surface with a cryogen free STM for the first time. Being totally cryogen-free, the system not only saves the running cost significantly but also enables uninterrupted data acquisitions and variable temperature measurements with much ease. In addition, the system is capable of coupling light to the STM junction by a pair of lens inside the UHV chamber. We expect that these enhanced capabilities could further broaden our views to the atomic-scale world. PMID- 27370454 TI - Scanning thermal microscopy based on a quartz tuning fork and a micro thermocouple in active mode (2omega method). AB - A novel probe for scanning thermal microscope using a micro-thermocouple probe placed on a Quartz Tuning Fork (QTF) is presented. Instead of using an external deflection with a cantilever beam for contact detection, an original combination of piezoelectric resonator and thermal probe is employed. Due to a non-contact photothermal excitation principle, the high quality factor of the QTF allows the probe-to-surface contact detection. Topographic and thermal scanning images obtained on a specific sample points out the interest of our system as an alternative to cantilevered resistive probe systems which are the most spread. PMID- 27370455 TI - Fabrication of all diamond scanning probes for nanoscale magnetometry. AB - The electronic spin of the nitrogen vacancy (NV) center in diamond forms an atomically sized, highly sensitive sensor for magnetic fields. To harness the full potential of individual NV centers for sensing with high sensitivity and nanoscale spatial resolution, NV centers have to be incorporated into scanning probe structures enabling controlled scanning in close proximity to the sample surface. Here, we present an optimized procedure to fabricate single-crystal, all diamond scanning probes starting from commercially available diamond and show a highly efficient and robust approach for integrating these devices in a generic atomic force microscope. Our scanning probes consisting of a scanning nanopillar (200 nm diameter, 1-2 MUm length) on a thin (<1 MUm) cantilever structure enable efficient light extraction from diamond in combination with a high magnetic field sensitivity (etaAC~50+/-20nT/Hz). As a first application of our scanning probes, we image the magnetic stray field of a single Ni nanorod. We show that this stray field can be approximated by a single dipole and estimate the NV-to-sample distance to a few tens of nanometer, which sets the achievable resolution of our scanning probes. PMID- 27370456 TI - Three-dimensional atomic force microscopy mapping at the solid-liquid interface with fast and flexible data acquisition. AB - We present the implementation of a three-dimensional mapping routine for probing solid-liquid interfaces using frequency modulation atomic force microscopy. Our implementation enables fast and flexible data acquisition of up to 20 channels simultaneously. The acquired data can be directly synchronized with commercial atomic force microscope controllers, making our routine easily extendable for related techniques that require additional data channels, e.g., Kelvin probe force microscopy. Moreover, the closest approach of the tip to the sample is limited by a user-defined threshold, providing the possibility to prevent potential damage to the tip. The performance of our setup is demonstrated by visualizing the hydration structure above the calcite (10.4) surface in water. PMID- 27370457 TI - Modularized architecture of address generation units suitable for real-time processing MR data on an FPGA. AB - In this paper, we describe a modular approach to the design of an Address Generation Unit (AGU). The approach consists of development of a generic Address Generation Core (AGC) as a basic building block and the construction of an AGU from the AGCs. We illustrate this concept with AGUs capable of handling 2D- and 3D-structured data, and as well as their setup for executing 2D and 3D FFT algorithms on a Field Programmable Gate Array (FPGA). The AGUs developed using our proposed method are simple and easily expandable. Furthermore, they can potentially support irregularly structured data which are often generated from the wide variety of pulse sequences in magnetic resonance imaging. Our experimental results show that these AGUs are capable of generating addresses with a user-predefined pattern automatically at the speed of one address per clock cycle and operate at clock rates up to 80 MHz. They can operate concurrently with other processes and thus do not introduce additional operation latencies. Although we focus on applying the developed AGUs to executing 2D and 3D FFT, we expect that the modular design method should have much wider applications. PMID- 27370458 TI - Low-temperature-compatible tunneling-current-assisted scanning microwave microscope utilizing a rigid coaxial resonator. AB - We present a design for a tunneling-current-assisted scanning near-field microwave microscope. For stable operation at cryogenic temperatures, making a small and rigid microwave probe is important. Our coaxial resonator probe has a length of approximately 30 mm and can fit inside the 2-in. bore of a superconducting magnet. The probe design includes an insulating joint, which separates DC and microwave signals without degrading the quality factor. By applying the SMM to the imaging of an electrically inhomogeneous superconductor, we obtain the spatial distribution of the microwave response with a spatial resolution of approximately 200 nm. Furthermore, we present an analysis of our SMM probe based on a simple lumped-element circuit model along with the near field microwave measurements of silicon wafers having different conductivities. PMID- 27370460 TI - Long-working-distance microscopic imaging in a turbid medium by use of an ultrafast optical Kerr gate. AB - We demonstrate a long-working-distance microscopic imaging of hidden objects in a turbid medium by use of an ultrafast optical Kerr gate (OKG). The results show that the working distance and the spatial resolution of the long-working-distance microscopic imaging system have been increased simultaneously compared with those of the conventional 4f OKG imaging systems. A compound lens consisting of a long focus achromatic doublet and a microscope objective is used to increase the long working distance and ensure the sufficient spatial resolution. The microscopic OKG imaging system with a working distance of 245 mm and a maximal spatial resolution of approximately 7 MUm has been performed. PMID- 27370459 TI - Development of an X-ray fluorescence holographic measurement system for protein crystals. AB - Experimental procedure and setup for obtaining X-ray fluorescence hologram of crystalline metalloprotein samples are described. Human hemoglobin, an alpha2beta2 tetrameric metalloprotein containing the Fe(II) heme active-site in each chain, was chosen for this study because of its wealth of crystallographic data. A cold gas flow system was introduced to reduce X-ray radiation damage of protein crystals that are usually fragile and susceptible to damage. A chi-stage was installed to rotate the sample while avoiding intersection between the X-ray beam and the sample loop or holder, which is needed for supporting fragile protein crystals. Huge hemoglobin crystals (with a maximum size of 8 * 6 * 3 mm(3)) were prepared and used to keep the footprint of the incident X-ray beam smaller than the sample size during the entire course of the measurement with the incident angle of 0 degrees -70 degrees . Under these experimental and data acquisition conditions, we achieved the first observation of the X-ray fluorescence hologram pattern from the protein crystals with minimal radiation damage, opening up a new and potential method for investigating the stereochemistry of the metal active-sites in biomacromolecules. PMID- 27370461 TI - Low-noise humidity controller for imaging water mediated processes in atomic force microscopy. AB - We demonstrate the construction of a novel low-noise continuous flow humidity controller and its integration with a commercial variable-temperature atomic force microscope fluid cell, allowing precise control of humidity and temperature at the sample during nanoscale measurements. Based on wet and dry gas mixing, the design allows a high mechanical stability to be achieved by means of an ultrasonic atomiser for the generation of water-saturated gas, improving upon previous bubbler-based architectures. Water content in the flow is measured both at the inflow and outflow of the fluid cell, enabling the monitoring of water condensation and icing, and allowing controlled variation of the sample temperature independently of the humidity. To benchmark the performance of the controller, the results of detailed noise studies and time-based imaging of the formation of ice layers on highly oriented pyrolytic graphite are shown. PMID- 27370462 TI - Extracting flat-field images from scene-based image sequences using phase correlation. AB - Flat-field image processing is an essential step in producing high-quality and radiometrically calibrated images. Flat-fielding corrects for variations in the gain of focal plane array electronics and unequal illumination from the system optics. Typically, a flat-field image is captured by imaging a radiometrically uniform surface. The flat-field image is normalized and removed from the images. There are circumstances, such as with remote sensing, where a flat-field image cannot be acquired in this manner. For these cases, we developed a phase correlation method that allows the extraction of an effective flat-field image from a sequence of scene-based displaced images. The method uses sub-pixel phase correlation image registration to align the sequence to estimate the static scene. The scene is removed from sequence producing a sequence of misaligned flat field images. An average flat-field image is derived from the realigned flat field sequence. PMID- 27370463 TI - Quartz tuning fork based microwave impedance microscopy. AB - Microwave impedance microscopy (MIM), a near-field microwave scanning probe technique, has become a powerful tool to characterize local electrical responses in solid state samples. We present the design of a new type of MIM sensor based on quartz tuning fork and electrochemically etched thin metal wires. Due to a higher aspect ratio tip and integration with tuning fork, such design achieves comparable MIM performance and enables easy self-sensing topography feedback in situations where the conventional optical feedback mechanism is not available, thus is complementary to microfabricated shielded stripline-type probes. The new design also enables stable differential mode MIM detection and multiple-frequency MIM measurements with a single sensor. PMID- 27370464 TI - Alternating current calorimeter for specific heat capacity measurements at temperatures below 10 K and pressures up to 10 GPa. AB - A developed alternating current calorimeter for measuring the absolute value of specific heat C of a very small sample under a pressure up to 10 GPa and low temperature below 10 K is described. A Bridgman anvil cell made of tungsten carbide with a top diameter of 3 mm is used. A hollow at the top prevents expansion of the sample space over the anvil top. Two chip resistors, which act as a thermometer and a heater, are mounted on the outer part of a copper beryllium gasket with a frying pan-like shape. Thus, the thermometer is not pressurized. In order to isolate the gasket from the anvil thermally, diamond powder with a grain size of 0.25 MUm is placed on the anvil top. Two jumps of C at the superconducting transitions of Pb (3.3 mg) and In (5.0 mg) are observed under various pressures up to 9 GPa, as clearly as those at the ambient pressure. PMID- 27370465 TI - Measurement of the B1g and B2g components of the elastoresistivity tensor for tetragonal materials via transverse resistivity configurations. AB - The elastoresistivity tensor mij,kl relates changes in resistivity to strains experienced by a material. As a fourth-rank tensor, it contains considerably more information about the material than the simpler (second-rank) resistivity tensor; in particular, for a tetragonal material, the B1g and B2g components of the elastoresistivity tensor (mxx,xx - mxx,yy and 2mxy,xy, respectively) can be related to its nematic susceptibility. Previous experimental probes of this quantity have focused exclusively on differential longitudinal elastoresistance measurements, which determine the induced resistivity anisotropy arising from anisotropic in-plane strain based on the difference of two longitudinal resistivity measurements. Here we describe a complementary technique based on transverse elastoresistance measurements. This new approach is advantageous because it directly determines the strain-induced resistivity anisotropy from a single transverse measurement. To demonstrate the efficacy of this new experimental protocol, we present transverse elastoresistance measurements of the 2mxy,xy elastoresistivity coefficient of BaFe2As2, a representative iron-pnictide that has previously been characterized via differential longitudinal elastoresistance measurements. PMID- 27370466 TI - Design and construction of a point-contact spectroscopy rig with lateral scanning capability. AB - The design and realization of a cryogenic rig for point-contact spectroscopy measurements in the needle-anvil configuration is presented. Thanks to the use of two piezoelectric nano-positioners, the tip can move along the vertical (z) and horizontal (x) direction and thus the rig is suitable to probe different regions of a sample in situ. Moreover, it can also form double point-contacts on different facets of a single crystal for achieving, e.g., an interferometer configuration for phase-sensitive measurements. For the later purpose, the sample holder can also host a Helmholtz coil for applying a small transverse magnetic field to the junction. A semi-rigid coaxial cable can be easily added for studying the behavior of Josephson junctions under microwave irradiation. The rig can be detached from the probe and thus used with different cryostats. The performance of this new probe has been tested in a Quantum Design PPMS system by conducting point-contact Andreev reflection measurements on Nb thin films over large areas as a function of temperature and magnetic field. PMID- 27370467 TI - Self-vibration cancellation of a novel bi-directional magnetized NdFeB/magnetostrictive/piezoelectric laminate. AB - A novel magnetoelectric (ME) laminated composite structure is proposed in this work, aiming to provide a good self-vibration cancellation performance under the magnetic field detection environment. The proposed structure consists of two Terfenol-D magnetostrictive alloy plates which are revised and length-magnetized by two NdFeB magnets bonded on the top surface of a thickness-polarized Pb(Zr, Ti)O3 (PZT) ceramic plate with separate electrodes. Experiments have shown that great vibration suppression up to 44 dB under harmonic disturbance was observed. The ME coefficient of the proposed structure also reaches up to ~29 mV/Oe at non resonance frequency and 758 mV/Oe at resonance frequency of 79 kHz which is ~2 times larger than the traditional L-T Terfenol-D/PZT bilayer configuration of the same scale. Such performance improvement is achieved based on the bi-directional magnetic field bias (HBias) of two NdFeB magnets in magnetostrictive layer, internal in-series electrical wire connection in piezoelectric layer. The proposed design has great potential to be used for industrial applications associated with heavy environmental vibration noise. PMID- 27370468 TI - A liquid jet setup for x-ray scattering experiments on complex liquids at free electron laser sources. AB - In this paper we describe a setup for x-ray scattering experiments on complex fluids using a liquid jet. The setup supports Small and Wide Angle X-ray Scattering (SAXS/WAXS) geometries. The jet is formed by a gas-dynamic virtual nozzle (GDVN) allowing for diameters ranging between 1 MUm and 20 MUm at a jet length of several hundred MUm. To control jet properties such as jet length, diameter, or flow rate, the instrument is equipped with several diagnostic tools. Three microscopes are installed to quantify jet dimensions and stability in situ. The setup has been used at several beamlines performing both SAXS and WAXS experiments. As a typical example we show an experiment on a colloidal dispersion in a liquid jet at the X-ray Correlation Spectroscopy instrument at the Linac Coherent Light Source free-electron laser. PMID- 27370469 TI - Optimization of current waveform tailoring for magnetically driven isentropic compression experiments. AB - The Thor pulsed power generator is being developed at Sandia National Laboratories. The design consists of up to 288 decoupled and transit time isolated capacitor-switch units, called "bricks," that can be individually triggered to achieve a high degree of pulse tailoring for magnetically driven isentropic compression experiments (ICE) [D. B. Reisman et al., Phys. Rev. Spec. Top.-Accel. Beams 18, 090401 (2015)]. The connecting transmission lines are impedance matched to the bricks, allowing the capacitor energy to be efficiently delivered to an ICE strip-line load with peak pressures of over 100 GPa. Thor will drive experiments to explore equation of state, material strength, and phase transition properties of a wide variety of materials. We present an optimization process for producing tailored current pulses, a requirement for many material studies, on the Thor generator. This technique, which is unique to the novel "current-adder" architecture used by Thor, entirely avoids the iterative use of complex circuit models to converge to the desired electrical pulse. We begin with magnetohydrodynamic simulations for a given material to determine its time dependent pressure and thus the desired strip-line load current and voltage. Because the bricks are connected to a central power flow section through transit time isolated coaxial cables of constant impedance, the brick forward-going pulses are independent of each other. We observe that the desired equivalent forward-going current driving the pulse must be equal to the sum of the individual brick forward-going currents. We find a set of optimal brick delay times by requiring that the L2 norm of the difference between the brick-sum current and the desired forward-going current be a minimum. We describe the optimization procedure for the Thor design and show results for various materials of interest. PMID- 27370470 TI - Wavelength-independent constant period spin-echo modulated small angle neutron scattering. AB - Spin-Echo Modulated Small Angle Neutron Scattering (SEMSANS) in Time-of-Flight (ToF) mode has been shown to be a promising technique for measuring (very) small angle neutron scattering (SANS) signals and performing quantitative Dark-Field Imaging (DFI), i.e., SANS with 2D spatial resolution. However, the wavelength dependence of the modulation period in the ToF spin-echo mode has so far limited the useful modulation periods to those resolvable with the limited spatial resolution of the detectors available. Here we present our results of an approach to keep the period of the induced modulation constant for the wavelengths utilised in ToF. This is achieved by ramping the magnetic fields in the coils responsible for creating the spatially modulated beam in synchronisation with the neutron pulse, thus keeping the modulation period constant for all wavelengths. Such a setup enables the decoupling of the spatial detector resolution from the resolution of the modulation period by the use of slits or gratings in analogy to the approach in grating-based neutron DFI. PMID- 27370471 TI - Elastic airtight container for the compaction of air-sensitive materials. AB - We report on the design and fabrication of a simple and versatile elastic canister for the compaction and hot-pressing of air-sensitive materials. This device consists of a heated double-ended floating die assembly, enclosed in a compressible stainless steel bellows that allows the action of an external hydraulic press in a uniaxial motion. The enclosure is fitted with vacuum, gas, and electrical feedthroughs to allow for atmosphere control, heating, and in situ process monitoring. The overall chamber is compact enough to be portable and transferrable into and out of a standard laboratory glovebox, thus eliminating the problem of exposing samples to ambient atmosphere during loading and unloading. Our design has been tested up to 600 degrees C and 7500 kg-force applied load, conditions within which transparent ceramics of anhydrous halides can be produced. PMID- 27370472 TI - Ultra-high vacuum compatible induction-heated rod casting furnace. AB - We report the design of a radio-frequency induction-heated rod casting furnace that permits the preparation of polycrystalline ingots of intermetallic compounds under ultra-high vacuum compatible conditions. The central part of the system is a bespoke water-cooled Hukin crucible supporting a casting mold. Depending on the choice of the mold, typical rods have a diameter between 6 mm and 10 mm and a length up to 90 mm, suitable for single-crystal growth by means of float-zoning. The setup is all-metal sealed and may be baked out. We find that the resulting ultra-high vacuum represents an important precondition for processing compounds with high vapor pressures under a high-purity argon atmosphere up to 3 bars. Using the rod casting furnace, we succeeded to prepare large high-quality single crystals of two half-Heusler compounds, namely, the itinerant antiferromagnet CuMnSb and the half-metallic ferromagnet NiMnSb. PMID- 27370473 TI - Development of a reaction cell for in-situ/operando studies of surface of a catalyst under a reaction condition and during catalysis. AB - Tracking surface chemistry of a catalyst during catalysis is significant for fundamental understanding of catalytic performance of the catalyst since it allows for establishing an intrinsic correlation between surface chemistry of a catalyst at its working status and its corresponding catalytic performance. Ambient pressure X-ray photoelectron spectroscopy can be used for in-situ studies of surfaces of different materials or devices in a gas. To simulate the gaseous environment of a catalyst in a fixed-bed a flowing gaseous environment of reactants around the catalyst is necessary. Here, we report the development of a new flowing reaction cell for simulating in-situ study of a catalyst surface under a reaction condition in gas of one reactant or during catalysis in a mixture of reactants of a catalytic reaction. The homemade reaction cell is installed in a high vacuum (HV) or ultrahigh vacuum (UHV) environment of a chamber. The flowing gas in the reaction cell is separated from the HV or UHV environment through well sealings at three interfaces between the reaction cell and X-ray window, sample door and aperture of front cone of an energy analyzer. Catalyst in the cell is heated through infrared laser beam introduced through a fiber optics interfaced with the reaction cell through a homemade feedthrough. The highly localized heating on the sample holder and Au-passivated internal surface of the reaction cell effectively minimizes any unwanted reactions potentially catalyzed by the reaction cell. The incorporated laser heating allows a fast heating and a high thermal stability of the sample at a high temperature. With this cell, a catalyst at 800 degrees C in a flowing gas can be tracked readily. PMID- 27370474 TI - Production of high density molecular beams with wide velocity scanning. AB - We describe modifications of a pulsed rotating supersonic beam source that improve performance, particularly increasing the beam density and sharpening the pulse profiles. As well as providing the familiar virtues of a supersonic molecular beam (high intensity, narrowed velocity distribution, and drastic cooling of rotation and vibration), the rotating source enables scanning the translational velocity over a wide range. Thereby, beams of any atom or molecule available as a gas can be slowed or speeded. Using Xe beams in the slowing mode, we have obtained lab speeds down to about 40 +/- 5 m/s with density near 10(11) cm(-3) and in the speeding mode lab speeds up to about 660 m/s and density near 10(14) cm(-3). We discuss some congenial applications. Providing low lab speeds can markedly enhance experiments using electric or magnetic fields to deflect, steer, or further slow polar or paramagnetic molecules. The capability to scan molecular speeds facilitates merging velocities with a codirectional partner beam, enabling study of collisions at very low relative kinetic energies, without requiring either beam to be slow. PMID- 27370475 TI - Implementation and application of a novel 2D magnetic twisting cytometry based on multi-pole electromagnet. AB - We implemented a novel 2D magnetic twisting cytometry (MTC) based on a previously reported multi-pole high permeability electromagnet, in which both the strength and direction of the twisting field can be controlled. Thanks to the high performance twisting electromagnet and the heterodyning technology, the measurement frequency has been extended to the 1 kHz range. In order to obtain high remanence of the ferromagnetic beads, a separate electromagnet with feedback control was adopted for the high magnetic field polarization. Our setup constitutes the first instrument which can be operated both in MTC mode and in magnetic tweezers (MT) mode. In this work, the mechanical properties of HL-1 cardiomyocytes were characterized in MTC mode. Both anisotropy and log-normal distribution of cell stiffness were observed, which agree with our previous results measured in MT mode. The response from these living cells at different frequencies can be fitted very well by the soft glassy rheology model. PMID- 27370476 TI - Accurate measurement of Seebeck coefficient. AB - In this work, it was investigated how to measure Seebeck coefficient accurately. The offset voltages, between the specimen and measurement wires, might influence the results measured significantly and should be eliminated during measuring process. They do not depend on temperature difference but on temperature and include two parts: the intrinsic component related to the materials and the random one related to the contact. The inversion method could eliminate the offset voltages more accurately than the traditional differential methods, and thus measure Seebeck coefficient more accurately. The accuracy of Seebeck coefficient measurement could be further improved by performing a proper temperature difference, optimizing temperature control, and using an electromagnetic screen. The most accurate results were obtained with a standard deviation of 0.06 MUV/K, measured under temperature difference of 1 K, temperature variation of 0.002 K, and with an iron electromagnetic screen. PMID- 27370477 TI - Simulation and experimental study of DC electric field distribution characteristics of rat hippocampal slices in vitro. AB - Direct current (DC) electric field is a noninvasive neuromodulation tool that can inhibit or facilitate excitability of neurons. Despite its efficacy, the dielectric constant of artificial cerebrospinal fluid and the position and direction of brain slices and other factors can affect the field intensity and distribution acting on the surface of rat hippocampus slices, thus causing errors. In this study, we describe a new analytical method optimized for DC electric fields acting on brain slices, and the design of an external DC electric field stimulator to allow scientific evaluation of brain slices. We investigated parameters regarding the uniformity of electric field distribution and identified the maximal parameters using the finite element method. Then, we selected and simplified slice images using magnetic resonance imaging data and calculated the electric field intensity of the original and simplified models. The electric field simulator induced action potential and excitatory postsynaptic current with intensities of 1, 5, and 10 V/m. This study describes the development of a new electric field stimulator and successfully demonstrates its practicability for scientific evaluation of tissue slices. PMID- 27370478 TI - Noise reduction of a Libbrecht-Hall style current driver. AB - The Libbrecht-Hall circuit is a well-known, low-noise current driver for narrow linewidth diode lasers. An important feature of the circuit is a current limit to protect the laser diode. As the current approaches the maximum limit, however, the noise in the laser current increases dramatically. This paper documents this behavior and explores simple circuit modifications to alleviate this issue. PMID- 27370479 TI - A repetitive long-pulse power generator based on pulse forming network and linear transformer driver. AB - A compact module for long-pulse power generator, based on Blumlein pulse forming network (PFN), was designed. Two Blumlein PFNs with L-type configuration and 20 Omega characteristic impedance were connected symmetrically to the primary coil of the linear transformer driver (LTD) and driven by an identical high voltage spark switch to ensure two Blumlein PFNs synchronizing operation. The output pulse of the module connected with 10 Omega water load is about 135 kV in amplitude and 200 ns in duration with a rise time of ~50 ns and a flat top of ~100 ns. On this basis, a repetitive long-pulse power generator based on PFN-LTD has been developed, which was composed of four modules. The following technical parameters of the generator were achieved on planar diode: output voltage amplitude of ~560 kV, output current amplitude of ~10 kA at a repetition rate of 25 Hz. The generator operates stable and outputs more than 10(4) pulses. Meanwhile, the continuous operating time of the generator is up to 60 s. PMID- 27370481 TI - Understanding and eliminating artifact signals from diffusely scattered pump beam in measurements of rough samples by time-domain thermoreflectance (TDTR). AB - Time-domain thermoreflectance (TDTR) is a pump-probe technique frequently applied to measure the thermal transport properties of bulk materials, nanostructures, and interfaces. One of the limitations of TDTR is that it can only be employed to samples with a fairly smooth surface. For rough samples, artifact signals are collected when the pump beam in TDTR measurements is diffusely scattered by the rough surface into the photodetector, rendering the TDTR measurements invalid. In this paper, we systemically studied the factors affecting the artifact signals due to the pump beam leaked into the photodetector and thus established the origin of the artifact signals. We find that signals from the leaked pump beam are modulated by the probe beam due to the phase rotation induced in the photodetector by the illumination of the probe beam. As a result of the modulation, artifact signals due to the leaked pump beam are registered in TDTR measurements as the out-of-phase signals. We then developed a simple approach to eliminate the artifact signals due to the leaked pump beam. We verify our leak pump correction approach by measuring the thermal conductivity of a rough InN sample, when the signals from the leaked pump beam are significant. We also discuss the advantages of our new method over the two-tint approach and its limitations. Our new approach enables measurements of the thermal conductivity of rough samples using TDTR. PMID- 27370480 TI - Current-limiting and ultrafast system for the characterization of resistive random access memories. AB - A new system for the ultrafast characterization of resistive switching phenomenon is developed to acquire the current during the Set and Reset process in a microsecond time scale. A new electronic circuit has been developed as a part of the main setup system, which is capable of (i) applying a hardware current limit ranging from nanoampers up to miliampers and (ii) converting the Set and Reset exponential gate current range into an equivalent linear voltage. The complete system setup allows measuring with a microsecond resolution. Some examples demonstrate that, with the developed setup, an in-depth analysis of resistive switching phenomenon and random telegraph noise can be made. PMID- 27370482 TI - Design and calibration of a novel transient radiative heat flux meter for a spacecraft thermal test. AB - Radiative heat flux measurement is significantly important for a spacecraft thermal test. To satisfy the requirements of both high accuracy and fast response, a novel transient radiative heat flux meter was developed. Its thermal receiver consists of a central thermal receiver and two thermal guarded annular plates, which ensure the temperature distribution of the central thermal receiver to be uniform enough for reasonably applying lumped heat capacity method in a transient radiative heat flux measurement. This novel transient radiative heat flux meter design can also take accurate measurements regardless of spacecraft surface temperature and incident radiation spectrum. The measurement principle was elaborated and the coefficients were calibrated. Experimental results from testing a blackbody furnace and an Xenon lamp show that this novel transient radiative heat flux meter can be used to measure transient radiative heat flux up to 1400 W/m(2) with high accuracy and the response time of less than 10 s. PMID- 27370483 TI - Capacitive displacement sensor for detecting planar submicrometer motion. AB - This paper describes the design of a very simple displacement sensor that measures the change in the position of an object by sensing the change in capacitance due to the movement of this object in the sensor fringing electric field. Two sensor geometries with small footprints were considered and several sensor variations were built and tested. At distances of approximately 0.5 MUm and 30 MUm, test results demonstrated that the sensors' resolution was in the order of tens of nanometers. PMID- 27370484 TI - Modeling and experiment of the suspended seismometer concept for attenuating the contribution of tilt motion in horizontal measurements. AB - Tilt-horizontal coupling in inertial sensors limits the performance of active isolation systems such as those used in gravitational wave detectors. Inertial rotation sensors can be used to subtract the tilt component from the signal produced by horizontal inertial sensors, but such techniques are often limited by the sensor noise of the tilt measurement. A different approach is to mechanically filter the tilt transmitted to the horizontal inertial sensor, as discussed in this article. This technique does not require an auxiliary rotation sensor and can produce a lower noise measurement. The concept investigated uses a mechanical suspension to isolate the inertial sensor from input tilt. Modeling and simulations show that such a configuration can be used to adequately attenuate the tilt transmitted to the instrument, while maintaining translation sensitivity in the frequency band of interest. The analysis is supported by experimental results showing that this approach is a viable solution to overcome the tilt problem in the field of active inertial isolation. PMID- 27370485 TI - Development of a suspension type sliding planar motion table using magnetic fluid lubrication. AB - A sliding planar motion table system that can be used for the lens driving actuator of a laser cutting machine was developed. The system uses magnetic fluid as the lubricant to avoid the leakage of lubricating oil under the table and reduce environmental pollution. The motion table is suspended from the guide surface by an attractive force generated by electromagnets to reduce the contact and frictional forces between the table and the guide surface. The table is capable of movement in one rotational and two translational directions over the guide surface using six electromagnets and three non-contact displacement sensors. Experimental results showed that the magnetic suspension of the table reduced the friction by 82.1% compared to the friction that would otherwise be generated by the dead weight of the table. Circular motion within a diameter of 2 mm was achieved with resolutions of 5 MUm and 20 MUrad in the translational and rotational directions, respectively. A bandwidth of higher than 100 Hz was also achieved in the three movement directions. PMID- 27370486 TI - Fault detection, isolation, and diagnosis of self-validating multifunctional sensors. AB - A novel fault detection, isolation, and diagnosis (FDID) strategy for self validating multifunctional sensors is presented in this paper. The sparse non negative matrix factorization-based method can effectively detect faults by using the squared prediction error (SPE) statistic, and the variables contribution plots based on SPE statistic can help to locate and isolate the faulty sensitive units. The complete ensemble empirical mode decomposition is employed to decompose the fault signals to a series of intrinsic mode functions (IMFs) and a residual. The sample entropy (SampEn)-weighted energy values of each IMFs and the residual are estimated to represent the characteristics of the fault signals. Multi-class support vector machine is introduced to identify the fault mode with the purpose of diagnosing status of the faulty sensitive units. The performance of the proposed strategy is compared with other fault detection strategies such as principal component analysis, independent component analysis, and fault diagnosis strategies such as empirical mode decomposition coupled with support vector machine. The proposed strategy is fully evaluated in a real self validating multifunctional sensors experimental system, and the experimental results demonstrate that the proposed strategy provides an excellent solution to the FDID research topic of self-validating multifunctional sensors. PMID- 27370487 TI - Theoretical and experimental study of the dynamic response of absorber-based, micro-scale, oscillatory probes for contact sensing applications. AB - This paper presents two models for predicting the frequency response of micro scale oscillatory probes. These probes are manufactured by attaching a thin fiber to the free end of one tine of a quartz tuning fork oscillator. In these studies, the attached fibers were either 75 MUm diameter tungsten or 7 MUm diameter carbon with lengths ranging from around 1 to 15 mm. The oscillators used in these studies were commercial 32.7 kHz quartz tuning forks. The first theoretical model considers lateral vibration of two beams serially connected and provides a characteristic equation from which the roots (eigenvalues) are extracted to determine the natural frequencies of the probe. A second, lumped model approximation is used to derive an approximate frequency response function for prediction of tine displacements as a function of a modal force excitation corresponding to the first mode of the tine in the absence of a fiber. These models are used to evaluate the effect of changes in both length and diameter of the attached fibers. Theoretical values of the natural frequencies of different modes show an asymptotic relationship with the length and a linear relationship with the diameter of the attached fiber. Similar results are observed from experiment, one with a tungsten probe having an initial fiber length of 14.11 mm incrementally etched down to 0.83 mm, and another tungsten probe of length 8.16 mm incrementally etched in diameter, in both cases using chronocoulometry to determine incremental volumetric material removal. The lumped model is used to provide a frequency response again reveals poles and zeros that are consistent with experimental measurements. Finite element analysis shows mode shapes similar to experimental microscope observations of the resonating carbon probes. This model provides a means of interpreting measured responses in terms of the relative motion of the tine and attached fibers. Of particular relevance is that, when a "zero" is observed in the response of the tine, one mode of the fiber is matched to the tine frequency and is acting as an absorber. This represents an optimal condition for contact sensing and for transferring energy to the fiber for fluid mixing, touch sensing, and surface modification applications. PMID- 27370488 TI - Magnetic field analysis of novel spherical actuators with three-dimensional pole arrays. AB - Spherical actuator is an electric device that can achieve multiple degree-of freedom rotary motions in a single joint. Permanent magnet array is a key factor that influences the output performance of electromagnetic spherical actuators. In this paper, a novel three-dimensional (3D) pole array is proposed to improve the system flux density and thus the output performance. Analysis of magnetic field distribution is extremely important for spherical actuators with 3D magnet arrays. Thus, the investigation of magnetic field is conducted in analytical, numerical, and experimental ways. The general solution of magnetic scalar potential in 3D space is formulated analytically based on Laplace's equations and spherical harmonics, and then specific solutions of the magnetic scalar potential and magnetic flux density are obtained by using boundary conditions. Numerical computation is utilized to validate the analytical model and to facilitate the observation of the magnetic field variation. A research prototype and a testing platform of magnetic field have been developed for experimental study. The testing platform can move the probe to any position around the spherical actuator and measure the flux density automatically. Experiments are conducted to obtain the flux distribution. Both numerical and experimental results validate the analytical model well. PMID- 27370489 TI - A flexible touch-pressure sensor array with wireless transmission system for robotic skin. AB - Human skin contains multiple receptors and is able to sense various stimuli such as temperature, touch, pressure, and deformation, with high sensitivity and resolution. The development of skin-like sensors capable of sensing these stimuli is of great importance for various applications such as robots, touch detection, temperature monitoring, and strain gauges. Great efforts have been made to develop high performance touch sensor and pressure sensor. Compared with general sensor, the touch-pressure sensor which is reported in this paper not only can measure large pressure but also has a high resolution in the small range so that it can feel slight touch. The sensor has a vertical structure. The upper layer is made of silicone rubber as the capacitive layer and the lower layer employs multiwall carbon nanotubes and carbon black filled silicone rubber as the resistive layer. The electrodes are made by conductive silver adhesives. In addition, the electrodes are connected to the pads on the top surface of the flexible printed circuit board by enamelled wires which made it easier to fabricate sensor array. The resolution of the touch-pressure sensor in the range of 0-10 N and 10-100 N are 0.1 N and 1 N, respectively. The experimental data of the sensor are sent by ZigBee wireless technology which reduces the complexity of the wiring and provides a convenient way to apply and maintain the sensor array. PMID- 27370490 TI - A miniature shoe-mounted orientation determination system for accurate indoor heading and trajectory tracking. AB - Tracking the position of pedestrian is urgently demanded when the most commonly used GPS (Global Position System) is unavailable. Benefited from the small size, low-power consumption, and relatively high reliability, micro-electro-mechanical system sensors are well suited for GPS-denied indoor pedestrian heading estimation. In this paper, a real-time miniature orientation determination system (MODS) was developed for indoor heading and trajectory tracking based on a novel dual-linear Kalman filter. The proposed filter precludes the impact of geomagnetic distortions on pitch and roll that the heading is subjected to. A robust calibration approach was designed to improve the accuracy of sensors measurements based on a unified sensor model. Online tests were performed on the MODS with an improved turntable. The results demonstrate that the average RMSE (root-mean-square error) of heading estimation is less than 1 degrees . Indoor heading experiments were carried out with the MODS mounted on the shoe of pedestrian. Besides, we integrated the existing MODS into an indoor pedestrian dead reckoning application as an example of its utility in realistic actions. A human attitude-based walking model was developed to calculate the walking distance. Test results indicate that mean percentage error of indoor trajectory tracking achieves 2% of the total walking distance. This paper provides a feasible alternative for accurate indoor heading and trajectory tracking. PMID- 27370491 TI - VESPA: The vibrational spectrometer for the European Spallation Source. AB - VESPA, Vibrational Excitation Spectrometer with Pyrolytic-graphite Analysers, aims to probe molecular excitations via inelastic neutron scattering. It is a thermal high resolution inverted geometry time-of-flight instrument designed to maximise the use of the long pulse of the European Spallation Source. The wavelength frame multiplication technique was applied to provide simultaneously a broad dynamic range (about 0-500 meV) while a system of optical blind choppers allows to trade flux for energy resolution. Thanks to its high flux, VESPA will allow the investigation of dynamical and in situ experiments in physical chemistry. Here we describe the design parameters and the corresponding McStas simulations. PMID- 27370492 TI - Optimized setup for two-dimensional convection experiments in thin liquid films. AB - We present a novel experimental setup to investigate two-dimensional thermal convection in a freestanding thin liquid film. Such films can be produced in a controlled way on the scale of 5-1000 nm. Our primary goal is to investigate convection patterns and the statistics of reversals in Rayleigh-Benard convection with varying aspect ratio. Additionally, questions regarding the physics of liquid films under controlled conditions can be investigated, like surface forces, or stability under varying thermodynamical parameters. The film is suspended in a frame which can be adjusted in height and width to span an aspect ratio range of Gamma = 0.16-10. The top and bottom frame elements can be set to specific temperature within T = 15 degrees C to 55 degrees C. A thickness to area ratio of approximately 10(8) enables only two-dimensional fluid motion in the time scales relevant for turbulent motion. The chemical composition of the film is well-defined and optimized for film stability and reproducibility and in combination with carefully controlled ambient parameters allows the comparison to existing experimental and numerical data. PMID- 27370493 TI - Towards the development of a hybrid-integrated chip interferometer for online surface profile measurements. AB - Non-destructive testing and online measurement of surface features are pressing demands in manufacturing. Thus optical techniques are gaining importance for characterization of complex engineering surfaces. Harnessing integrated optics for miniaturization of interferometry systems onto a silicon wafer and incorporating a compact optical probe would enable the development of a handheld sensor for embedded metrology applications. In this work, we present the progress in the development of a hybrid photonics based metrology sensor device for online surface profile measurements. The measurement principle along with test and measurement results of individual components has been presented. For non-contact measurement, a spectrally encoded lateral scanning probe based on the laser scanning microscopy has been developed to provide fast measurement with lateral resolution limited to the diffraction limit. The probe demonstrates a lateral resolution of ~3.6 MUm while high axial resolution (sub-nanometre) is inherently achieved by interferometry. Further the performance of the hybrid tuneable laser and the scanning probe was evaluated by measuring a standard step height sample of 100 nm. PMID- 27370494 TI - A gas circulation and purification system for gas-cell-based low-energy RI-beam production. AB - A gas circulation and purification system was developed at the RIKEN Radioactive Isotope Beam Factory that can be used for gas-cell-based low-energy RI-beam production. A high-flow-rate gas cell filled with one atmosphere of buffer gas (argon or helium) is used for the deceleration and thermalization of high-energy RI-beams. The exhausted buffer gas is efficiently collected using a compact dry pump and returned to the gas cell with a recovery efficiency of >97%. The buffer gas is efficiently purified using two gas purifiers as well as collision cleaning, which eliminates impurities in the gas. An impurity level of one part per billion is achieved with this method. PMID- 27370495 TI - New portable instrument for the measurement of thermal conductivity in gas process conditions. AB - The development of high temperature gas sensors for the monitoring and determination of thermophysical properties of complex process mixtures at high temperatures faces several problems, related with the materials compatibility, active sensing parts sensitivity, and lifetime. Ceramic/thin metal films based sensors, previously developed for the determination of thermal conductivity of molten materials up to 1200 degrees C, were redesigned, constructed, and applied for thermal conductivity measuring sensors. Platinum resistance thermometers were also developed using the same technology, to be used in the temperature measurement, which were also constructed and tested. A new data acquisition system for the thermal conductivity sensors, based on a linearization of the transient hot-strip model, including a portable electronic bridge for the measurement of the thermal conductivity in gas process conditions was also developed. The equipment is capable of measuring the thermal conductivity of gaseous phases with an accuracy of 2%-5% up to 840 degrees C (95% confidence level). The development of sensors up to 1200 degrees C, present at the core of the combustion chambers, will be done in a near future. PMID- 27370496 TI - An apparatus to estimate the hydrodynamic coefficients of autonomous underwater vehicles using water tunnel testing. AB - Hydrodynamic coefficients or hydrodynamic derivatives of autonomous underwater vehicles (AUVs) play an important role in their development and maneuverability. The most popular way of estimating their coefficients is to implement captive model tests such as straight line tests and planar motion mechanism (PMM) tests in the towing tanks. This paper aims to develop an apparatus based on planar experiments of water tunnel in order to estimate hydrodynamic derivatives due to AUVs' acceleration and velocity. The capability of implementing straight line tests and PMM ones using mechanical oscillators located in the downstream flow of the model is considered in the design procedure of the system. The hydrodynamic derivatives that resulted from the acceleration and velocity of the AUV model were estimated using the apparatus that we developed. Static and dynamics test results were compared for the similar derivatives. The findings showed that the system provided the basis for conducting static tests, i.e., straight-line and dynamic tests that included pure pitch and pure heave. By conducting such tests in a water tunnel, we were able to eliminate errors related to the time limitation of the tests and the effects of surface waves in the towing tank on AUVs with applications in the deep sea. PMID- 27370497 TI - An instrument to measure mechanical up-conversion phenomena in metals in the elastic regime. AB - Crystalline materials, such as metals, are known to exhibit deviation from a simple linear relation between strain and stress when the latter exceeds the yield stress. In addition, it has been shown that metals respond to varying external stress in a discontinuous way in this regime, exhibiting discrete releases of energy. This crackling noise has been extensively studied both experimentally and theoretically when the metals are operating in the plastic regime. In our study, we focus on the behavior of metals in the elastic regime, where the stresses are well below the yield stress. We describe an instrument that aims to characterize non-linear mechanical noise in metals when stressed in the elastic regime. In macroscopic systems, this phenomenon is expected to manifest as a non-stationary noise modulated by external disturbances applied to the material, a form of mechanical up-conversion of noise. The main motivation for this work is for the case of maraging steel components (cantilevers and wires) in the suspension systems of terrestrial gravitational wave detectors. Such instruments are planned to reach very ambitious displacement sensitivities, and therefore mechanical noise in the cantilevers could prove to be a limiting factor for the detectors' final sensitivities, mainly due to non-linear up conversion of low frequency residual seismic motion to the frequencies of interest for the gravitational wave observations. We describe here the experimental setup, with a target sensitivity of 10(-15) m/Hz in the frequency range of 10-1000 Hz, a simple phenomenological model of the non-linear mechanical noise, and the analysis method that is inspired by this model. PMID- 27370498 TI - Characterization for Cassie-Wenzel wetting transition based on the force response in the process of squeezing liquid drops by two parallel superhydrophobic surfaces. AB - Application of superhydrophobic surfaces is partly limited by the escaping of the entrapped air beneath the liquid sitting on the superhydrophobic surfaces, i.e., the so-called Cassie-Wenzel wetting transition. Here, to characterize this wetting transition, a linear force response relation with certain abnormal systematic deflection showing the wetting transition information is constructed for the process of squeezing the test liquid drop by two parallel structured (superhydrophobic) surfaces. The linear force response relation is validated by replotting the experimental data from the former work. And then the wetting transition information is investigated on a numerically generated force response curve with certain errors by taking into account the liquid pressure variation during the wetting transition. Results show that the wetting transition can cause an obvious bulge on the linear force response curve. We believe that this method has a potential application in characterizing the robustness of superhydrophobic surfaces. PMID- 27370499 TI - Development of a compact, fiber-coupled, six degree-of-freedom measurement system for precision linear stage metrology. AB - A compact, fiber-coupled, six degree-of-freedom measurement system which enables fast, accurate calibration, and error mapping of precision linear stages is presented. The novel design has the advantages of simplicity, compactness, and relatively low cost. This proposed sensor can simultaneously measure displacement, two straightness errors, and changes in pitch, yaw, and roll using a single optical beam traveling between the measurement system and a small target. The optical configuration of the system and the working principle for all degrees-of-freedom are presented along with the influence and compensation of crosstalk motions in roll and straightness measurements. Several comparison experiments are conducted to investigate the feasibility and performance of the proposed system in each degree-of-freedom independently. Comparison experiments to a commercial interferometer demonstrate error standard deviations of 0.33 MUm in straightness, 0.14 MUrad in pitch, 0.44 MUradin yaw, and 45.8 MUrad in roll. PMID- 27370500 TI - Investigations of the contact bounce behaviors and relative dynamic welding phenomena for electromechanical relay. AB - Dynamic welding, being the principal mechanism of sticking failure, correlates closely with the contact bounce of electromechanical relay. The typical waveforms of dynamic contact force and contact voltage at making and breaking process are obtained with the use of a new designed test rig. The variations in bounce time, bounce numbers, last bounce duration, and relevant welding force are investigated in the electrical endurance test. It is determined that the welding strength and the welding probability are increased with the reduced stationary force. The degradation physical mechanism is present to better understand the relationship between dynamic welding and operation characteristics of electromechanical relay. PMID- 27370502 TI - Note: Single-shot time-domain spectroscopy and spatial profiling of terahertz pulses from intense laser systems. AB - Single-shot terahertz time-domain spectroscopy is presented with directly encoded spatial resolution. A single reflective echelon and multiple semi-cylindrical lenses are used to obtain both the temporal waveform and the spatial distribution of the terahertz field. This system can be used to rapidly characterize terahertz pulses generated by high power pulsed laser systems, which themselves suffer from large pulse energy and spectrum fluctuations. PMID- 27370501 TI - Towards a wearable near infrared spectroscopic probe for monitoring concentrations of multiple chromophores in biological tissue in vivo. AB - The first wearable multi-wavelength technology for functional near-infrared spectroscopy has been developed, based on a custom-built 8-wavelength light emitting diode (LED) source. A lightweight fibreless probe is designed to monitor changes in the concentrations of multiple absorbers (chromophores) in biological tissue, the most dominant of which at near-infrared wavelengths are oxyhemoglobin and deoxyhemoglobin. The use of multiple wavelengths enables signals due to the less dominant chromophores to be more easily distinguished from those due to hemoglobin and thus provides more complete and accurate information about tissue oxygenation, hemodynamics, and metabolism. The spectroscopic probe employs four photodiode detectors coupled to a four-channel charge-to-digital converter which includes a charge integration amplifier and an analogue-to-digital converter (ADC). Use of two parallel charge integrators per detector enables one to accumulate charge while the other is being read out by the ADC, thus facilitating continuous operation without dead time. The detector system has a dynamic range of about 80 dB. The customized source consists of eight LED dies attached to a 2 mm * 2 mm substrate and encapsulated in UV-cured epoxy resin. Switching between dies is performed every 20 ms, synchronized to the detector integration period to within 100 ns. The spectroscopic probe has been designed to be fully compatible with simultaneous electroencephalography measurements. Results are presented from measurements on a phantom and a functional brain activation study on an adult volunteer, and the performance of the spectroscopic probe is shown to be very similar to that of a benchtop broadband spectroscopy system. The multi-wavelength capabilities and portability of this spectroscopic probe will create significant opportunities for in vivo studies in a range of clinical and life science applications. PMID- 27370503 TI - Note: A calibration method to determine the lumped-circuit parameters of a magnetic probe. AB - This paper describes a novel method to determine the lumped-circuit parameters of a magnetic inductive probe for calibration by using Helmholtz coils with high frequency power supply (frequency range: 10 kHz-400 kHz). The whole calibration circuit system can be separated into two parts: "generator" circuit and "receiver" circuit. By implementing the Fourier transform, two analytical lumped circuit models, with respect to these separated circuits, are constructed to obtain the transfer function between each other. Herein, the precise lumped circuit parameters (including the resistance, inductance, and capacitance) of the magnetic probe can be determined by fitting the experimental data to the transfer function. Regarding the fitting results, the finite impedance of magnetic probe can be used to analyze the transmission of a high-frequency signal between magnetic probes, cables, and acquisition system. PMID- 27370504 TI - Note: An iterative algorithm to improve colloidal particle locating. AB - Confocal microscopy of colloids combined with digital image processing has become a powerful tool in soft matter physics and materials science. Together, these techniques enable locating and tracking of more than half a million individual colloidal particles at once. However, despite improvements in locating algorithms that improve position accuracy, it remains challenging to locate all particles in a densely packed, three dimensional colloid without erroneously identifying the same particle more than once. We present a simple iterative algorithm that mitigates both the "missed particle" and "double counting" problems while simultaneously reducing sensitivity to the specific choice of input parameters. It is also useful for analyzing images with spatially varying brightness in which a single set of input parameters is not appropriate for all particles. The algorithm is easy to implement and compatible with existing particle locating software. PMID- 27370505 TI - Note: Easy-to-maintain electron cyclotron resonance (ECR) plasma sputtering apparatus featuring hybrid waveguide and coaxial cables for microwave delivery. AB - The branched-waveguide electron cyclotron resonance plasma sputtering apparatus places quartz windows for transmitting microwaves into the plasma source not in the line of sight of the target. However, the quartz windows must be replaced after some time of operation. For maintenance, the loop waveguide branching from the T-junction must be dismounted and re-assembled accurately, which is a time consuming job. We investigated substituting the waveguide branches with two sets of coaxial cables and waveguide/coaxial cable converters to simplify assembly as far as connection and disconnection go. The resulting hybrid system worked well for the purposes of plasma generation and film deposition. PMID- 27370506 TI - Note: Contamination-free loading of lithium metal into a nozzle source. AB - This note describes a system for transferring a load of high purity lithium metal into a molecular or cluster beam source. A hot loading vessel is thoroughly baked out while empty and overpressured with argon. A clean Li rod is then dropped in through a long narrow tube. The thoroughly degassed interior of the vessel and the rapid melting of the inserted rod facilitate contamination-free transfer of the highly reactive liquid metal into the source oven. PMID- 27370507 TI - Note: A component-level frequency tunable isolator for vibration-sensitive chips using SMA beams. AB - This note presents a component-level frequency tunable isolator for vibration sensitive chips. The isolator employed 8 U-shaped shape memory alloy (SMA) beams to support an isolation island (used for mounting chips). Due to the temperature induced Young's modulus variation of SMA, the system stiffness of the isolator can be controlled through heating the SMA beams. In such a way, the natural frequency of the isolator can be tuned. A prototype was fabricated to evaluate the concept. The test results show that the natural frequency of the isolator can be tuned in the range of 64 Hz-97 Hz by applying different heating strategies. Moreover, resonant vibration can be suppressed significantly (the transmissibility decreases about 65% near the resonant frequency) using a real time tuning method. PMID- 27370508 TI - Note: Experimental observation of nano-channel pattern in light sheet laser interference nanolithography system. AB - We experimentally observed nano-channel-like pattern in a light-sheet based interference nanolithography system. The optical system created nano-channel-like patterned illumination. Coherent counter-propagating light sheets are made to interfere at and near geometrical focus along the propagation z-axis. This results in the formation of nano-channel-like pattern (of size ~ 300 nm and inter channel periodicity of ~337.5 nm) inside the sample due to constructive and destructive interference. In addition, the technique has the ability to generate large area patterning using larger light-sheets. Exciting applications are in the broad field of nanotechnology (nano-electronics and nano-fluidics). PMID- 27370509 TI - Note: A simple sample transfer alignment for ultra-high vacuum systems. AB - The alignment of ultra-high-vacuum sample transfer systems can be problematic when there is no direct line of sight to assist the user. We present the design of a simple and cheap system which greatly simplifies the alignment of sample transfer devices. Our method is based on the adaptation of a commercial digital camera which provides live views from within the vacuum chamber. The images of the camera are further processed using an image recognition and processing code which determines any misalignments and reports them to the user. Installation has proven to be extremely useful in order to align the sample with respect to the transfer mechanism. Furthermore, the alignment software can be easily adapted for other systems. PMID- 27370510 TI - Note: Rheological properties of structured fluids: Improvements on the slotted plate apparatus. AB - This note is to report on improvements to the slotted-plate device that allows for the determination of viscosity and yield stress in structured systems such as suspensions and electro-rheological fluids. The improvements address the determination of very low yield stress values that occur, for example, with biological fluids, as well as viscosity measurements at extremely low shear rates. PMID- 27370512 TI - Erratum: "Ultrafast time measurements by time-correlated single photon counting coupled with superconducting single photon detector" [Rev. Sci. Instrum. 87, 053117 (2016)]. PMID- 27370513 TI - Periodontal bone height of exclusive narghile smokers compared with exclusive cigarette smokers. AB - OBJECTIVE: To compare the periodontal bone height (PBH) of exclusive narghile smokers (ENS) with that of exclusive cigarette smokers (ECS). METHODS: Tunisian males aged 20-35 years who have been ENS for more than five narghile-years or ECS for more than five pack-years were recruited to participate in this comparative cross-sectional study. Information about oral health habits and tobacco consumption were gathered using a predetermined questionnaire. Plaque levels were recorded in four sites using the plaque index of Loe and Silness. The PBH was measured mesially and distally from digital panoramic radiographs of each tooth and expressed as a percentage of the root length. A PBH level <= 0.70 was applied as a cutoff reference value signifying bone loss. Student t-test and Chi(2) test were used to compare quantitative and qualitative data of both groups. RESULTS: There were no significant differences between the ENS (n=60) and ECS (n=60) groups regarding age and the consumed quantities of tobacco (28 +/- 4 vs. 27 +/- 5 years, 7 +/- 3 narghile-years vs. 8 +/- 3 pack-years, respectively). Compared with the ECS group, the ENS group had a significantly higher plaque index (mean +/- SD values were 1.54 +/- 0.70 vs. 1.84 +/- 0.73, respectively). However, the two groups had similar means of PBH (0.85 +/- 0.03 vs. 0.86 +/- 0.04) and tooth brushing frequencies (1.1 +/- 0.8 vs. 0.9 +/- 0.6 a day, respectively) and had similar bone loss frequencies (15% vs. 12%, respectively). CONCLUSIONS: Both ENS and ECS exhibited the same PBH reduction, which means that both types of tobacco smoking are associated with periodontal bone loss. PMID- 27370514 TI - The Impact of Couple Therapy on Service Utilization among Military Veterans: The Moderating Roles of Pretreatment Service Utilization and Premature Termination. AB - Couple therapy reduces relational and individual distress and may affect utilization of other health services, particularly among higher service utilizers. Although average decreases in service utilization are predicted among recipients of couple therapy, low utilizers of services may appropriately increase use. The relationship between couple therapy and service utilization was examined among a sample of 179 U.S. military veterans who received treatment in Veterans Affairs (VA) specialty couple therapy clinics. Consistent with hypotheses, overall mental and physical health visits decreased from the 12 months preceding couple therapy to the 12 months following treatment. Moderator analyses showed that decreases were greatest among individuals who were rated by their therapist as having completed a full course of couple therapy, suggesting that change was attributable to intervention. Pretreatment service utilization also moderated observed change-higher utilizers' use of services decreased substantially, whereas lower utilizers' slightly increased. Cost analyses revealed that the estimated per person mean cost in our sample decreased by $930.33 in the year following compared to the year prior to couple therapy, as per 2008 VA cost data. As service utilization data were only available for one partner and only for 1 year posttherapy, the true magnitude of this effect may be underestimated. Our findings are relevant to policy makers as they demonstrate that couple therapy reduces average service utilization and associated costs and addresses calls for analyses of cost effectiveness of systemic interventions. PMID- 27370515 TI - In this issue August 2016. PMID- 27370516 TI - Alternative therapies and postoperative vomiting. PMID- 27370517 TI - Perioperative management in children with chronic pain. AB - Children with chronic pain often undergo surgery and effective perioperative management of their pain can be challenging. Identification of the pediatric chronic pain patient preoperatively and development of a perioperative pain plan may help ensure a safer and more comfortable perioperative course. Successful management usually requires multiple different classes of analgesics, regional anesthesia, and adjunctive nonpharmacological therapies. Neuropathic and oncological pain can be especially difficult to treat and usually requires an individualized approach. PMID- 27370518 TI - The usefulness of systematic reviews of animal studies: shooting the messenger. PMID- 27370519 TI - Reply to Hooijmans, Carlijn; Wever, Kimberley; Ritskes-Hoitinga, Merel; Scheffer, Gert Jan, regarding their comment 'The usefulness of systematic reviews of animal studies; shooting the messenger'. PMID- 27370520 TI - Reply to Snow et al. regarding their comment 'A call to solve the puzzle together by building an evidence base for perioperative management of children with Autism Spectrum Disorder (ASD). PMID- 27370521 TI - Reply to Ekeoduru, Rhashedah; Matuszczak, Maria; Lin, Michael, regarding their comment 'Correspondence' regarding 'The presumed central nervous system effects of rocuronium in a neonate and its reversal with sugammadex' by Langley, McFadzean & McCormack. PMID- 27370522 TI - Preemptive analgesia for acute postoperative pain management in children. PMID- 27370523 TI - Pontocerebellar hypoplasia, malignant hyperthermia, and inappropriate use of secondary references. PMID- 27370524 TI - Comment on 'Utility of screening questionnaire, obesity, neck circumference, and sleep polysomnography to predict sleep-disordered breathing in children and adolescents. PMID- 27370525 TI - Looking Beyond Structure: Membrane Phospholipids of Skeletal Muscle Mitochondria. AB - Skeletal muscle mitochondria are highly dynamic and are capable of tremendous expansion to meet cellular energetic demands. Such proliferation in mitochondrial mass requires a synchronized supply of enzymes and structural phospholipids. While transcriptional regulation of mitochondrial enzymes has been extensively studied, there is limited information on how mitochondrial membrane lipids are generated in skeletal muscle. Herein we describe how each class of phospholipids that constitute mitochondrial membranes are synthesized and/or imported, and summarize genetic evidence indicating that membrane phospholipid composition represents a significant modulator of skeletal muscle mitochondrial respiratory function. We also discuss how skeletal muscle mitochondrial phospholipids may mediate the effect of diet and exercise on oxidative metabolism. PMID- 27370526 TI - Impact of a computer-assisted Screening, Brief Intervention and Referral to Treatment on reducing alcohol consumption among patients with hazardous drinking disorder in hospital emergency departments. The randomized BREVALCO trial. AB - OBJECTIVE: To assess the impact of a computer-assisted Screening, Brief Intervention, and Referral to Treatment (SBIRT) on daily consumption of alcohol by patients with hazardous drinking disorder detected after systematic screening during their admission to an emergency department (ED). DESIGN: Two-arm, parallel group, multicentre, randomized controlled trial with a centralised computer generated randomization procedure. SETTING: Four EDs in university hospitals located in the Paris area in France. PARTICIPANTS: Patients admitted in the ED for any reason, with hazardous drinking disorder detected after systematic screening (i.e., Alcohol Use Disorder Identification Test score >=5 for women and 8 for men OR self-reported alcohol consumption by week >=7 drinks for women and 14 for men). INTERVENTIONS: The experimental intervention was computer-assisted SBIRT and the comparator was a placebo-controlled intervention (i.e., a computer assisted education program on nutrition). Interventions were administered in the ED and followed by phone reinforcements at 1 and 3 months. MAIN OUTCOME MEASURE: The primary outcome was the mean number of alcohol drinks per day in the previous week, at 12 months. Results From May 2005 to February 2011, 286 patients were randomized to the computer-assisted SBIRT and 286 to the comparator intervention. The two groups did not differ in the primary outcome, with an adjusted mean difference of 0.12 (95% confidence interval, -0.88 to 1.11). CONCLUSIONS: There was no additional benefit of the computer-assisted alcohol SBIRT as compared with the computer-assisted education program on nutrition among patients with hazardous drinking disorder detected by systematic screening during their admission to an ED. PMID- 27370528 TI - Hepta-, hexa-, penta-, tetra-, and trisaccharide resin glycosides from three species of Ipomoea and their antiproliferative activity on two glioma cell lines. AB - Six new partially acylated resin glycosides were isolated from convolvulin of Ipomoea purga, Ipomoea stans, and Ipomoea murucoides (Convolvulaceae). The structures of compounds 1-6 were elucidated by a combination of NMR spectroscopy and mass spectrometry. The structure of jalapinoside B (1) consists of a hexasaccharide core bonded to an 11-hydroxytetradecanoic (convolvulinic) acid forming a macrolactone acylated by a 2-methylbutanoyl, a 3-hydroxy-2 methylbutanoyl, and a quamoclinic acid B units. Purginoic acid A (2) contains a hexasaccharide core bonded to a convolvulinic acid acylated by a 3-hydroxy-2 methylbutanoyl unit. Stansin A (4) is an ester-type heterodimer, and consists of two stansoic acid A (3) units, acylated by 2-methylbutanoic and 3-hydroxy-2 methylbutanoic acids. The site of lactonization was located at C-3 of Rhamnose, and the position for the ester linkage of the monomeric unit B on the macrolactone unit A was established as C-4 of the terminal rhamnose. Compounds 5 and 6 are glycosidic acids. Murucinic acid II (5) is composed of a pentasaccharide core bonded to an 11-hydroxyhexadecanoic (jalapinolic) acid, acylated by an acetyl unit. Stansinic acid I (6) is a tetrasaccharide core bonded to a jalapinolic acid, acylated by 2-methylbutanoyl and 3-hydroxy-2 methylbutanoyl units. Preliminary testing showed the cytotoxicity of compounds 1 6 toward OVCAR and UISO-SQC-1 cancer cell lines. In addition, compound 1 showed an antiproliferative activity on glioma C6 and RG2 tumor cell lines. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27370527 TI - Determinants of willingness to enroll in opioid agonist treatment among opioid dependent people who inject drugs in Ukraine. AB - BACKGROUND: Coverage with opioid agonist treatments (OAT) that include methadone and buprenorphine is low (N=8400, 2.7%) for the 310,000 people who inject drugs (PWID) in Ukraine. In the context of widespread negative attitudes toward OAT in the region, patient-level interventions targeting the barriers and willingness to initiate OAT are urgently needed. METHODS: A sample of 1179 PWID with opioid use disorder not currently on OAT from five regions in Ukraine was assessed using multivariable logistic regression for independent factors related to willingness to initiate OAT, stratified by their past OAT experience. RESULTS: Overall, 421 (36%) PWID were willing to initiate OAT. Significant adjusted odds ratios (aOR) for covariates associated with the willingness to initiate OAT common for both groups included: higher injection frequency (previously on OAT: aOR=2.7; never on OAT: aOR=1.8), social and family support (previously on OAT: aOR=2.0; never on OAT: aOR=2.0), and positive attitude towards OAT (previously on OAT: aOR=1.3; never on OAT: aOR=1.4). Among participants previously on OAT, significant correlates also included: HIV-negative status (aOR=2.6) and depression (aOR=2.7). Among participants never on OAT, however, living in Kyiv (aOR=4.8) or Lviv (aOR=2.7), previous imprisonment (aOR=1.5), registration at a Narcology service (aOR=1.5) and recent overdose (aOR=2.6) were significantly correlated with willingness to initiate OAT. CONCLUSIONS: These findings emphasize the need for developing interventions aimed to eliminate existing negative preconceptions regarding OAT among PWID with opioid use disorder in Ukraine, which should be tailored to meet the needs of specific characteristics of PWID in geographically distinct setting based upon injection frequency, prior incarceration, and psychiatric and HIV status. PMID- 27370529 TI - Rosai-Dorfman disease: Familiar yet enigmatic. PMID- 27370530 TI - Fear of Hypoglycemia in Children and Adolescents and Their Parents with Type 1 Diabetes. AB - Hypoglycemia is a frequent occurrence in children and adolescents with type 1 diabetes. A variety of efforts have been made to standardize the definition of hypoglycemia and to define one of its most significant psychosocial consequences fear of hypoglycemia (FOH). In addition to documenting the experience of FOH in children and adolescents type 1 diabetes and their parents, studies have investigated the relations between FOH and glycemic control and diabetes technology use. This review provides a summary of the recent FOH literature as it applies to pediatric type 1 diabetes. PMID- 27370531 TI - Muscle atrophy and fatty infiltration in rotator cuff tears: Can surgery stop muscular degenerative changes? AB - BACKGROUND: Rotator cuff tears are closely related with muscle atrophy and fatty infiltration and both affect healing after surgical treatment. The aim of this study was to compare surgical versus conservative management of medium-to-large reparable rotator cuff tears. METHODS: Forty-one patients with clinical and radiological (MRI) diagnosis of medium-to-large rotator cuff tears were retrospectively identified and divided into two groups: Group A, arthroscopic repair; Group B, conservative treatment. At follow-up (T1) all patients underwent a new clinical (VAS, SST, Constant and Relative Constant Scale) and radiological evaluation (MRI). RESULTS: When comparing the two groups at T1 (mean follow-up: Group A, 50 months; Group B, 61 months), we registered better results in Group A in the SST (p < 0.05), the VAS score (p < 0.01), the Constant and the Relative Constant Scale (p < 0.05). Radiological evaluation did not show a significant increase of fatty infiltration (p = 0.16) in Group A (no progression in 15 out of 17 patients -82.3%-, and an increase in 2 out of 17 patients -11.7%-), while in Group B a significant increase was detected (p < 0.01) in all patients; in regard to muscle atrophy, no cases of progression were detected in Group A (4 out of 17 patients -23.5%- showed an increased post-operative supraspinatus trophysm), while a significant worsening (p < 0.05) was found in Group B. In Group B a significant worsening of tendon retraction (p < 0.01) and of tear size (p = 0.01) was also detected. CONCLUSIONS: Surgical treatment of complete rotator cuff tears seems to decrease the irreversible changes that involve muscle belly. PMID- 27370532 TI - Acute social stress before the planning phase improves memory performance in a complex real life-related prospective memory task. AB - Successful execution of intentions, but also the failure to recall are common phenomena in everyday life. The planning, retention, and realization of intentions are often framed as the scientific concept of prospective memory. The current study aimed to examine the influence of acute stress on key dimensions of complex "real life" prospective memory. To this end, we applied a prospective memory task that involved the planning, retention, and performance of intentions during a fictional holiday week. Forty healthy males participated in the study. Half of the subjects were stressed with the Socially Evaluated Cold Pressor Test (SECPT) before the planning of intentions, and the other half of the participants underwent a control procedure at the same time. Salivary cortisol was used to measure the effectiveness of the SECPT stress induction. Stressed participants did not differ from controls in planning accuracy. However, when we compared stressed participants with controls during prospective memory retrieval, we found statistically significant differences in PM across the performance phase. Participants treated with the SECPT procedure before the planning phase showed improved prospective memory retrieval over time, while performance of controls declined. Particularly, there was a significant difference between the stress and control group for the last two days of the holiday week. Interestingly, control participants showed significantly better performance for early than later learned items, which could be an indicator of a primacy effect. This differential effect of stress on performance was also found in time- and event-dependent prospective memory. Our results demonstrate for the first time, that acute stress induced before the planning phase may improve prospective memory over the time course of the performance phase in time- and event-dependent prospective memory. Our data thus indicate that prospective memory can be enhanced by acute stress. PMID- 27370533 TI - Contribution of environmental media to cryptosporidiosis and giardiasis prevalence in Tehran: a focus on surface waters. AB - The occurrences of Cryptosporidium and Giardia in surface sources of drinking water in Tehran were monitored, using US EPA method 1623.1. The prevalence ratios (PR) of positive samples among other media (animal's stools, vegetables, and human's stools) were also estimated from literature data. The density of Giardia and Cryptosporidium in water samples were 0.129 +/- 0.069 cysts/L and 0.005 +/- 0.002 oocysts/L, respectively. Estimated PR in vegetables, animal stools, surface waters, and human stools were 6.65, 20.42, 21.05, and 4.28 % for Cryptosporidium and 6.46, 17.13, 73.68, and 15.65 % for Giardia, respectively. These reveal the importance of surface waters' and animal stools' roles in the prevalence of cryptosporidiosis and giardiasis in Tehran's population. Giardia's prevalence in untreated surface waters in Tehran was found 3.5 times as much as Cryptosporidium while this found 2.3 times on a global scale. Moreover, the prevalence of giardiasis to cryptosporidiosis infections in Tehran's human population was 3.65. These values could be a clue to attribute the infections to the occurrence of parasites in surface waters. Significant (p < 0.05) associations were observed between rainfalls and presence of Giardia (r = 0.62) and Cryptosporidium (r = 0.60) in surface waters. In autumn, rainfalls can increase the parasites occurrences in surface waters. Significant (p < 0.05) difference on the density of parasites was found between some seasons using Kruskal-Wallis and multiple comparison tests. A significant correlation (r = 0.86) between Giardia and Cryptosporidium densities also confirms the common sources of pollution in surface waters. Findings suggest that untreated surface waters in Tehran may be a potential route of human exposure to protozoan parasites. PMID- 27370534 TI - Assessments of levels, potential ecological risk, and human health risk of heavy metals in the soils from a typical county in Shanxi Province, China. AB - A total of 128 surface soil samples were collected, and eight heavy metals, including As, Cd, Cr, Cu, Pb, Ni, Zn, and Hg, were analyzed for their concentrations, potential ecological risks, and human health risks. The mean concentrations of these eight metals were lower than the soil environmental quality standards in China, while they were slightly higher than the background values in Shanxi Province. The enrichment factor, coefficient variation, and potential ecological risk index were used to assess the pollution and eco-risk level of heavy metals, among which, Cd and Hg showed higher pollution levels and potential risks than the others in the studied area. Moreover, multivariate geostatistical analysis suggested that Hg originated mainly from point sources such as industrial emissions, while agricultural activity is the predominant factor for Cd. The human health risk assessment indicated that non-carcinogenic values were below the threshold values. The total carcinogenic risks due to As, Cr, and Ni were within the acceptable range for adults, while for children, they were higher than the threshold value (1.0E-04), indicating that children are facing higher threat to heavy metals in soils. These results provide basic information on heavy metal pollution control and human health risk assessment management in the study regions. PMID- 27370535 TI - Phthalate esters in water and surface sediments of the Pearl River Estuary: distribution, ecological, and human health risks. AB - The Pearl River Estuary (PRE) is vulnerable due to the increasingly serious environmental pollution, such as phthalate esters (PAEs) contaminants, from the Pearl River Delta (PRD). The concentrations of six US Environmental Protection Agency (USEPA) priority PAEs in water and surface sediments collected from the PRD's six main estuaries in spring, summer, and winter 2013 were measured by GC MS. Total PAEs (?6PAEs) concentrations were from 0.5 to 28.1 MUg/L and from 0.88 to 13.6 MUg/g (dry weight (DW)) in water and surface sediments, respectively. The highest concentration was detected in summer. Higher concentrations of PAEs were found in Yamen (YM) and Humen (HM) areas than the other areas. Bis(2 ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) were the dominant PAEs in the investigated areas, contributing between 61 and 95 % of the PAEs in water and from 85 to 98 % in surface sediments. Based on risk quotients (RQs), DEHP posed greater ecological risks to the studied aquatic environments than other measured compounds. Little human health risk from the target PAEs was identified. PMID- 27370536 TI - Oxidation of methane in biotrickling filters inoculated with methanotrophic bacteria. AB - The oxidation of methane (CH4) using biofilters has been proposed as an alternative to mitigate anthropogenic greenhouse gas emissions with a low concentration of CH4 that cannot be used as a source of energy. However, conventional biofilters utilize organic packing materials that have a short lifespan, clogging problems, and are commonly inoculated with non-specific microorganisms leading to unpredictable CH4 elimination capacities (EC) and removal efficiencies (RE). The main objective of this work was to characterize the oxidation of CH4 in two biotrickling filters (BTFs) packed with polyethylene rings and inoculated with two methanotrophic bacteria, Methylomicrobium album and Methylocystis sp., in order to determine EC and CO2 production (pCO2) when using a specific inoculum. The repeatability of the results in both BTFs was determined when they operated at the same inlet load of CH4. A dynamic mathematical model that describes the CH4 abatement in the BTFs was developed and validated using mass transfer and kinetic parameters estimated independently. The results showed that EC and pCO2 of the BTFs are not identical but very similar for all the conditions tested. The use of specific inoculum has shown a faster startup and higher EC per unit area (0.019 gCH4 m-2 h-1) in comparison to most of the previous studies at the same CH4 load rate (23.2 gCH4 m-3 h-1). Global mass balance showed that the maximum reduction of CO2 equivalents was 98.5 gCO2eq m-3 h-1. The developed model satisfactorily described CH4 abatement in BTFs for a wide range of conditions. PMID- 27370537 TI - Optimizing COD removal from greywater by photoelectro-persulfate process using Box-Behnken design: assessment of effluent quality and electrical energy consumption. AB - Greywater (GW) is a potential source for water reuse in various applications. However, GW treatment is still a vital issue in water reuse in cases of environmental standards and risk to public health. This study investigates optimization and modeling of a hybrid process for COD removal from GW. Persulfate (PS) was simultaneously activated by electrogenerated ferrous ion (EC) and UV to generate sulfate radical. Photoelectro-persulfate (PEPS) was optimized by Box Behnken design and the effects of four variables (pH, PS dosage, current density, and electrolysis time) were evaluated on COD removal. The results and several coefficients showed that the obtained model was acceptable for predicting the COD removal. Moreover, under optimum conditions (pH = 6.9, PS = 8.8 mM, current density = 2.0 mA/cm(2), and 49.3 min electrolysis time), BOD5, turbidity, TSS, phosphate, and UV254 were effectively removed and COD and BOD5 values reached to discharge standards. Different configurations of the processes were assessed for COD removal. The order of COD removal efficiency followed: PS < Fe(II) < UV/PS <= Fe(II)/PS < Fe(II)/PS/UV < electrocoagulation <= electrocoagulation/UV < electro PS < PEPS. The monitoring PS concentration during 60 min reaction time in the aforesaid processes indicated that PEPS could remarkably activate PS. The solution pH was also monitored and related results revealed that the presence of PS during the 10 min first time decreased pH value while production of hydroxide ion at cathode increased pH significantly. Finally, the contribution of electrochemical process in the electrical energy consumption was far less than that of photolysis process in hybrid PEPS process. PMID- 27370538 TI - An analytical model for contaminant transport in landfill composite liners considering coupled effect of consolidation, diffusion, and degradation. AB - One-dimensional mathematical model is developed to investigate the behavior of contaminant transport in landfill composite liner system considering coupled effect of consolidation, diffusion, and degradation. The first- and second-type bottom boundary conditions are used to derive the steady-state and quasi-steady state analytical solutions. The concentration profiles obtained by the proposed analytical solution are in good agreement with those obtained by the laboratory tests. The bottom concentration and flux of the soil liners can be greatly reduced when the degradation effect and porosity changing are considered. For the case under steady-state, the bottom flux and concentration for the case with t 1/2 =10 years can be 2.8 and 5.5 times lower than those of the case with t 1/2 =100 years, respectively. The bottom concentration and flux of the soil liners can be greatly reduced when the coefficient of volume compressibility decreases. For quasi-steady-state and with t 1/2 = 10 years, the bottom flux and concentration for the case with m v = 0.02/MPa can be 17.4 and 21 times lower than the case with m v = 0.5/MPa. This may be due to the fact that the true fluid velocity induced by consolidation is greater for the case with high coefficient of volume compressibility. The bottom flux for the case with single compacted clay liner (CCL) can be 1.5 times larger than that for the case with GMB/CCL considering diffusion and consolidation for DCM. The proposed analytical model can be used for verification of more complicated numerical models and assessment of the coupled effect of diffusion, consolidation, and degradation on contaminant transport in landfill liner systems. PMID- 27370539 TI - Altered Expression of Specific Transcription Factors of Th17 (RORgammat, RORalpha) and Treg Lymphocytes (FOXP3) by Peripheral Blood Mononuclear Cells from Patients with Multiple Sclerosis. AB - The imbalance in Th17/Treg cell-related responses plays an important role in the pathogenesis of multiple sclerosis (MS). The development of Th17- and Treg cells is regulated by specific transcription factors-RORgammat and RORalpha-and FOXP3, respectively. The aim was to determine the expression of RORgammat, RORalpha, and FOXP3 in peripheral blood mononuclear cells (PBMCs) from MS patients following in vitro stimulation. The PBMCs from 22 MS patients and 20 healthy subjects were cultured in the presence of 10 MUg/ml MOG, 10 MUg/ml PHA, or without stimulation. The PBMCs were incubated at 37 degrees C for 24 h, and then the messenger RNA (mRNA) expression of RORgammat, RORalpha, and FOXP3 was determined by real-time PCR. The expression of RORgammat and RORalpha was increased in non-stimulated, MOG-stimulated, and PHA-stimulated PBMCs from MS patients in comparison with same cultures from the healthy group (P < 0.01, P < 0.01, and P < 0.02 for RORgammat; P < 0.001, P < 0.001, and P < 0.05, for RORalpha, respectively). The FOXP3 expression in non-stimulated PBMCs from MS patients was significantly lower than that in equal culture from healthy subjects (P < 0.05). There were no significant differences between healthy subjects and MS patients regarding the expression of FOXP3 mRNA by MOG-stimulated and PHA-stimulated PBMCs. These results showed an imbalance in Th17/Treg cells at transcription factor levels with a deviation toward Th17 cell in MS. The correction of Th17/Treg balance at transcription levels should be considered to design novel therapeutic strategies for MS treatment. PMID- 27370540 TI - WTAP Expression Predicts Poor Prognosis in Malignant Glioma Patients. AB - Wilms' tumor 1-associating protein (WTAP) interacts with the Wilms' tumor 1 gene. Although originally classified as a tumor suppressor, WTAP was later found to be over-expressed in glioblastoma which is regarded as a grade IV astrocytoma. However, the expression in other glioma grades and the relationship between WTAP expression and the prognosis of glioma patients are still unknown. In this study, we investigated WTAP expression in 169 different types of glioma cases using western blot analysis and immunohistochemistry assay. Further, we evaluated the association of WTAP expression with clinicopathological characteristics using chi square test and Spearman's correlation test. We used univariate and multivariate Cox regression analyses to evaluate the independency of diferent WTAP expression. Then, the survival curves were calculated using the Kaplan-Meier method. Results showed that WTAP was over-expressed in glioma tissues, and the expression was closely correlated with glioma grade. Moreover, high WTAP expression was correlated with poor postoperative survival in glioma patients. WTAP may serve as a novel prognostic marker. PMID- 27370541 TI - Soluble BAFF Level Is Not Correlated to Mycobacterium avium Subspecies Paratuberculosis Antibodies and Increases After Interferon-beta Therapy in Multiple Sclerosis Patients. AB - B cells are being recognized as one of the major players in the pathogenesis of multiple sclerosis (MS). The B cell activating factor (BAFF) system plays an essential role in B cell homeostasis and function in the periphery. Mycobacterium avium subspecies paratuberculosis (MAP) has been previously associated to MS in Sardinia. Antibodies against a MAP surface protein, MAP_2694, have been found significantly associated to MS patients, and this response was modified by interferon-beta therapy. Increased BAFF levels following IFN-beta therapy have been also described in MS patients. In this study, we evaluated whether soluble BAFF levels are comparable in men and women affected by MS and performed a correlation of the reported BAFF increase in MS patients under IFN-beta therapy with changes of humoral response against MAP_2694. For these reasons, we investigated 44 MS patients before and after IFN-beta therapy. A significant difference of BAFF levels was found between men and women with MS; moreover, we confirmed that IFN-beta therapy strongly induces BAFF serum levels, but this was not related to the modification of immunological response against MAP_2694. In conclusion, our study highlights that IFN-beta therapy induces the potent B cell survival factor BAFF without alterations of the humoral immune response against MAP. PMID- 27370542 TI - Intrathecal morphine verse femoral nerve block for pain control in total knee arthroplasty: A meta-analysis from randomized control trials. AB - OBJECTIVE: Total knee arthroplasty (TKA) is usually associated with postoperative pain. The objective of this systematic review and meta-analysis was to evaluate the effectiveness and safety of femoral nerve block compared with intrathecal morphine for pain management after TKA. METHODS: Potentially relevant literature was identified from electronic databases including Medline, PubMed, Embase, ScienceDirect and the Cochrane Library. Gray academic studies were also identified from the reference of included literature. There was no language restriction. Pooling of data was carried out using Stata 11.0. RESULTS: Four randomized controlled trials (RCTs) involving 185 patients met the inclusion criteria. The meta-analysis indicated that there were no significant differences in terms of Visual Analog Scale (VAS) score at 6 h (standard mean difference (SMD) = -0.09, 95% CI: -1.62 to 1.43, P = 0.903), 12 h (weighted mean difference (WMD) = 1.84, 95% CI: -8.01 to 11.69, P = 0.714) or 24 h (WMD = 1.56, 95% CI: 14.31 to 17.42, P = 0.8474). No significant difference were found regarding morphine consumption at 6 h (WMD = -0.84, 95% CI: -2.52 to 0.85, P = 0.332), 12 h (WMD = 0.031, 95% CI: -3.304 to 0.3366, P = 0.985), 24 h (WMD = 0.21, 95% CI: 7.32 to 7.75, P = 0.956) or incidence of postoperative vomit and nausea (risk difference (RD) = -0.01, 95% CI: -0.15 to 0.12, P = 0.847). There was a significant difference between the groups in terms of the risk of itching postoperatively (RD = 0.41, 95% CI: 0.29 to 0.54, P < 0.001). CONCLUSIONS: Femoral nerve block provides equal postoperative pain control compared with intrathecal morphine following total knee arthroplasty, although there were fewer side effects in the FNB groups. In contrast, FNB was performed with an additional procedure and required a special apparatus. Both methods are effective at pain control following TKA. PMID- 27370543 TI - Patient focused registries can improve health, care, and science. PMID- 27370544 TI - The effects of maternal alcohol use disorders on childhood relationships and mental health. AB - PURPOSE: Despite millions of children living in the turmoil of their parents' active alcoholism or the aftermath of past abuse, research to date has not (1) provided a comprehensive examination of the effects of maternal alcohol use disorders (AUDs) on children's social ties outside of their relationships with parents, or (2) considered whether the number and quality of childhood social ties alter the effects of maternal AUDs on children's mental health. METHOD: Using data from the National Longitudinal Surveys of Youth 1979 Children and Young Adults, analysis examined the influence of maternal AUDs on the number and quality of children's ties with siblings, extended family and family friends, peers, and neighborhood members. The analysis also considered how children's social ties influenced the association between maternal AUDs and children's internalizing and externalizing problems. RESULTS: Children of alcoholic mothers had similarly sized networks but more distant relationships with siblings and friends, negative interactions with classmates, and isolating neighborhoods. Controlling for these aspects of children's social ties substantially reduced mental health disparities between children of alcoholic mothers and other children. CONCLUSIONS: Findings support the view that maternal alcohol use disorders have the potential to damage children's mental health while also setting into motion long-term relationship problems. Future research should examine the networks of children who experience parental AUDs to further clarify the social processes that link parental AUDs to children's mental health. PMID- 27370545 TI - [Not Available]. PMID- 27370546 TI - [Not Available]. PMID- 27370547 TI - [Not Available]. PMID- 27370548 TI - [Not Available]. PMID- 27370550 TI - [Not Available]. PMID- 27370549 TI - [Not Available]. PMID- 27370551 TI - [Not Available]. PMID- 27370552 TI - [Not Available]. PMID- 27370553 TI - [Not Available]. PMID- 27370554 TI - [Not Available]. PMID- 27370555 TI - [Not Available]. PMID- 27370556 TI - [Not Available]. PMID- 27370557 TI - [Not Available]. PMID- 27370558 TI - [Not Available]. PMID- 27370559 TI - [Not Available]. PMID- 27370560 TI - [Not Available]. PMID- 27370561 TI - [Not Available]. PMID- 27370562 TI - [Not Available]. PMID- 27370563 TI - [Not Available]. PMID- 27370564 TI - [Not Available]. PMID- 27370565 TI - [Not Available]. PMID- 27370566 TI - [Not Available]. PMID- 27370568 TI - [Not Available]. PMID- 27370567 TI - [Not Available]. PMID- 27370569 TI - MethPed: an R package for the identification of pediatric brain tumor subtypes. AB - BACKGROUND: DNA methylation profiling of pediatric brain tumors offers a new way of diagnosing and subgrouping these tumors which improves current clinical diagnostics based on histopathology. We have therefore developed the MethPed classifier, which is a multiclass random forest algorithm, based on DNA methylation profiles from many subgroups of pediatric brain tumors. RESULTS: We developed an R package that implements the MethPed classifier, making it easily available and accessible. The package can be used for estimating the probability that an unknown sample belongs to each of nine pediatric brain tumor diagnoses/subgroups. CONCLUSIONS: The MethPed R package efficiently classifies pediatric brain tumors using the developed MethPed classifier. MethPed is available via Bioconductor: http://bioconductor.org/packages/MethPed/. PMID- 27370571 TI - Emergence and spread of G3P[8] rotaviruses possessing an equine-like VP7 and a DS 1-like genetic backbone in the Basque Country (North of Spain), 2015. AB - In March 2015, an atypical G3P[8] rotavirus with an equine-like VP7 gene was detected in Gipuzkoa (Basque Country, Spain) and spread contributing significantly to the seasonal epidemic. The strain was identified in fecal samples collected from 68 patients, mainly children from rural and urban settings with acute gastroenteritis, representing 14.9% of the 455 rotavirus strains genotyped between July 2014 and June 2015. Seven patients (10.3%) were hospitalized. Full genome analysis of six of these strains revealed a DS-1-like genotype constellation, G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2, and showed that most genome segments shared the highest nucleotide sequence identity with strains isolated in Japan, Thailand, Australia and the Philippines. The strains of Gipuzkoa were similar to novel G3P[8] reassortant rotaviruses with an equine-like VP7 gene and a DS-1-like genetic backbone that emerged in the Asia-Pacific Region in 2013. The study highlights the circulation of these atypical rotaviruses outside the Asia-Pacific Region of origin, and their emergence in a European Region. Due to their unusual genotype constellation, these strains pose a challenge for the rotavirus strain surveillance, since G-/P-typing, the most commonly used classification system, cannot identify this type of intergenogroup reassortants. PMID- 27370574 TI - [Not Available]. PMID- 27370572 TI - Giardiasis in NSW: Identification of Giardia duodenalis assemblages contributing to human and cattle cases, and an epidemiological assessment of sporadic human giardiasis. AB - Two genetic assemblages (A and B) of the protozoan parasite species, Giardia duodenalis, infect humans, domestic animals and wildlife. In New South Wales, Australia, over 2000 sporadic human giardiasis cases are reported annually, but parasite sources and links between sporadic cases are unknown. This study describes G. duodenalis assemblages contributing to human and cattle cases in NSW, and examines demographic, spatial, and temporal distributions of NSW human infections and G. duodenalis assemblages. Genotyping by PCR-restriction fragment length polymorphism of the glutamate dehydrogenase (gdh) gene identified G. duodenalis assemblage B as the most common (86%) cause of infection among human cases (n=165). Approximately 37% of cattle DNA samples were PCR positive (18S rRNA, gdh), and G. duodenalis assemblages E (69%) or B (31%) were identified from these samples. Human assemblage A was more common among older age groups, and seasonality in the geographic dispersal of human assemblage A was observed. The results of this study indicate G. duodenalis assemblage B is highly prevalent among humans in NSW, and the potential for cross-species transmission exists between humans and cattle in this region. Spatio-temporal and demographic distributions of human assemblage A and B are highlighted, and risk factors associated with these dispersal patterns warrants further research. PMID- 27370575 TI - [Not Available]. PMID- 27370573 TI - Cultural Validation and Reliability of the Turkish Version of the Geriatric Pain Measure in the Elderly. AB - BACKGROUND: Many pain problems and untreated pain are known to adversely affect the quality of life of the elderly. The aim of this study was to evaluate the psychometric properties of the Turkish version of the Geriatric Pain Measure (GPM) in the elderly. METHODS: This research was carried out on 244 elderly who were recruited from a university hospital. Content validity, criterion validity, and factorial construct validity were used to test the validity stages; internal consistency and item analysis were used to determine the reliability of the Turkish GPM. RESULTS: For content validity, the Kendall goodness-of-fit correlation test was performed (Kendall's W = 0.275, P = 0.07). The criterion validity of the GPM was determined by item analysis based on the differences between averages of upper-lower group item scores that were significant (t = 38.597, P < 0.005). According to the factor analysis results of the scale, factor loadings were significant, with standardized loadings ranging from 0.40 to 0.87. Cronbach's alpha was found to be reliable for the total scale (0.85), and subscale alpha coefficients ranged from 0.67 to 0.93. The item analysis of the scale showed that all of the correlations between the items of the scale were significant. CONCLUSIONS: The Turkish version of the GPM was found to be a reliable and valid tool to measure the quality and severity of pain in the elderly. PMID- 27370570 TI - Bioactive natural products for chemoprevention and treatment of castration resistant prostate cancer. AB - Prostate cancer (PCa), a hormonally-driven cancer, ranks first in incidence and second in cancer related mortality in men in most Western industrialized countries. Androgen and androgen receptor (AR) are the dominant modulators of PCa growth. Over the last two decades multiple advancements in screening, treatment, surveillance and palliative care of PCa have significantly increased quality of life and survival following diagnosis. However, over 20% of patients initially diagnosed with PCa still develop an aggressive and treatment-refractory disease. Prevention or treatment for hormone-refractory PCa using bioactive compounds from marine sponges, mushrooms, and edible plants either as single agents or as adjuvants to existing therapy, has not been clinically successful. Major advancements have been made in the identification, testing and modification of the existing molecular structures of natural products. Additionally, conjugation of these compounds to novel matrices has enhanced their bio-availability; a big step towards bringing natural products to clinical trials. Natural products derived from edible plants (nutraceuticals), and common folk-medicines might offer advantages over synthetic compounds due to their broader range of targets, as compared to mostly single target synthetic anticancer compounds; e.g. kinase inhibitors. The use of synthetic inhibitors or antibodies that target a single aberrant molecule in cancer cells might be in part responsible for emergence of treatment refractory cancers. Nutraceuticals that target AR signaling (epigallocatechin gallate [EGCG], curcumin, and 5alpha-reductase inhibitors), AR synthesis (ericifolin, capsaicin and others) or AR degradation (betulinic acid, di-indolyl diamine, sulphoraphane, silibinin and others) are prime candidates for use as adjuvant or mono-therapies. Nutraceuticals target multiple pathophysiological mechanisms involved during cancer development and progression and thus have potential to simultaneously inhibit both prostate cancer growth and metastatic progression (e.g., inhibition of angiogenesis, epithelial-mesenchymal transition (EMT) and proliferation). Given their multi-targeting properties along with relatively lower systemic toxicity, these compounds offer significant therapeutic advantages for prevention and treatment of PCa. This review emphasizes the potential application of some of the well-researched natural compounds that target AR for prevention and therapy of PCa. PMID- 27370576 TI - [Not Available]. PMID- 27370577 TI - [Not Available]. PMID- 27370578 TI - [Not Available]. PMID- 27370580 TI - [Not Available]. PMID- 27370579 TI - [Not Available]. PMID- 27370581 TI - [Not Available]. PMID- 27370583 TI - [Not Available]. PMID- 27370582 TI - [Not Available]. PMID- 27370584 TI - [Not Available]. PMID- 27370586 TI - [Not Available]. PMID- 27370585 TI - [Not Available]. PMID- 27370587 TI - [Not Available]. PMID- 27370588 TI - [Not Available]. PMID- 27370589 TI - [Not Available]. PMID- 27370590 TI - [Not Available]. PMID- 27370591 TI - [Not Available]. PMID- 27370592 TI - [Not Available]. PMID- 27370593 TI - [Not Available]. PMID- 27370594 TI - [Not Available]. PMID- 27370595 TI - [Not Available]. PMID- 27370596 TI - [Not Available]. PMID- 27370597 TI - [Not Available]. PMID- 27370598 TI - [Not Available]. PMID- 27370599 TI - [Not Available]. PMID- 27370600 TI - [Not Available]. PMID- 27370601 TI - The Right to Health in Old Age: Israeli Professionals' and Older Persons' Perspectives. AB - OBJECTIVES: To develop a better understanding of the right to health in old age through the personal knowledge and experience of older persons and professionals in Israel. METHODS: A qualitative research method was adopted based on focus groups. Information was collected through four focus groups with 33 participants. RESULTS: Three main themes emerged: The first focused on the older persons' self positioning vis-a-vis the health-care system. The second illustrated the verbal means chosen by the participants to situate the health-care system itself. The third elaborated on the institutional and cultural processes involved in upholding health rights in old age. DISCUSSION: Future discussions regarding conceptualization of the right to health in old age should relate to its human aspects, that is, communication and interaction, and the older person's knowledge, participation, and involvement in shaping the medical services that they receive. PMID- 27370602 TI - Electroencephalography-Derived Sensory and Motor Network Topology in Multiple Sclerosis Fatigue. AB - People with multiple sclerosis (MS) frequently complain of excessive fatigue, which is the most disabling symptom for half of them. While the few drugs used to treat MS fatigue are of limited utility, we recently observed the efficacy of a personalized neuromodulation treatment. Here, we aim at strengthening knowledge of the brain network changes that occur when MS fatigue increases, using graph theory. We collected electroencephalographic (EEG; 23 or 64 channels) data in resting state with eyes open in 27 relapsing-remitting (RR) patients with mild MS (EDSS <=2), suffering a wide range of fatigue as scored by the modified Fatigue Impact Scale (mFIS) (2-69, within a total range 0-84). To estimate graph theory small-world index (SW), we calculated the lagged linear coherence between EEG cortical eLORETA sources, in the standard frequency bands delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), beta2 (20-30 Hz), and gamma (30-45 Hz). We calculated the SW of these undirected and weighted networks separately in the four left and right frontal (motor) and parieto occipito-temporal (sensory) brain networks. A correlative analysis demonstrated increased fatigue symptoms along with the SW specifically in the Sensory network of the left dominant hemisphere in the beta1 band (Pearson's r = 0.404, P = .020). Our study indicates a specific involvement of the dominant-hemisphere sensory network in MS fatigue. It suggests that compensatory neuromodulation interventions could enhance efficacy in relieving this debilitating symptom by targeting this area. PMID- 27370604 TI - Combination of Imatinib Mesylate and AKT Inhibitor Provides Synergistic Effects in Preclinical Study of Gastrointestinal Stromal Tumor. AB - PURPOSE: Gastrointestinal stromal tumors (GIST) generally harbor activating mutations in the receptor tyrosine kinase KIT or in the related platelet-derived growth factor receptor alpha (PDGFRA). GIST treated with imatinib mesylate or second-line therapies that target mutant forms of these receptors generally escape disease control and progress over time. Inhibiting additional molecular targets may provide more substantial disease control. Recent studies have implicated the PI3K/AKT pathway in the survival of imatinib mesylate-resistant GIST cell lines and tumors. EXPERIMENTAL DESIGN: Here, we performed in vitro and in vivo studies evaluating the novel combination of imatinib mesylate with the AKT inhibitor MK-2206 in GIST. Whole-transcriptome sequencing (WTS) of xenografts was performed to explore the molecular aspects of tumor response to this novel combination and to potentially identify additional therapeutic targets in GIST. RESULTS: This drug combination demonstrated significant synergistic effects in a panel of imatinib mesylate-sensitive and -resistant GIST cell lines. Furthermore, combination therapy provided significantly greater efficacy, as measured by tumor response and animal survival, in imatinib mesylate-sensitive GIST xenografts as compared with treatment with imatinib mesylate or MK-2206 alone. WTS implicated two neural genes, brain expressed X-linked 1 and neuronal pentraxin I, whose expression was significantly upregulated in combination-treated tumors compared with tumors treated with the two monotherapies. CONCLUSIONS: These studies provide strong preclinical justification for combining imatinib mesylate with an AKT inhibitor as a front-line therapy in GIST. In addition, the WTS implicated the BCL-2/BAX/BAD apoptotic pathway as a potential mechanism for this enhanced combination effect. Clin Cancer Res; 23(1); 171-80. (c)2016 AACR. PMID- 27370603 TI - TRNT1 deficiency: clinical, biochemical and molecular genetic features. AB - BACKGROUND: TRNT1 (CCA-adding transfer RNA nucleotidyl transferase) enzyme deficiency is a new metabolic disease caused by defective post-transcriptional modification of mitochondrial and cytosolic transfer RNAs (tRNAs). RESULTS: We investigated four patients from two families with infantile-onset cyclical, aseptic febrile episodes with vomiting and diarrhoea, global electrolyte imbalance during these episodes, sideroblastic anaemia, B lymphocyte immunodeficiency, retinitis pigmentosa, hepatosplenomegaly, exocrine pancreatic insufficiency and renal tubulopathy. Other clinical features found in children include sensorineural deafness, cerebellar atrophy, brittle hair, partial villous atrophy and nephrocalcinosis. Whole exome sequencing and bioinformatic filtering were utilised to identify recessive compound heterozygous TRNT1 mutations (missense mutation c.668T>C, p.Ile223Thr and a novel splice mutation c.342+5G>T) segregating with disease in the first family. The second family was found to have a homozygous TRNT1 mutation (c.569G>T), p.Arg190Ile, (previously published). We found normal mitochondrial translation products using passage matched controls and functional perturbation of 3' CCA addition to mitochondrial tRNAs (tRNA(Cys), tRNA(LeuUUR) and tRNA(His)) in fibroblasts from two patients, demonstrating a pathomechanism affecting the CCA addition to mt-tRNAs. Acute management of these patients included transfusion for anaemia, fluid and electrolyte replacement and immunoglobulin therapy. We also describe three-year follow-up findings after treatment by bone marrow transplantation in one patient, with resolution of fever and reversal of the abnormal metabolic profile. CONCLUSIONS: Our report highlights that TRNT1 mutations cause a spectrum of disease ranging from a childhood-onset complex disease with manifestations in most organs to an adult onset isolated retinitis pigmentosa presentation. Systematic review of all TRNT1 cases and mutations reported to date revealed a distinctive phenotypic spectrum and metabolic and other investigative findings, which will facilitate rapid clinical recognition of future cases. PMID- 27370606 TI - New Strategies in Esophageal Carcinoma: Translational Insights from Signaling Pathways and Immune Checkpoints. AB - Esophageal cancer remains a highly lethal malignancy in which relatively modest therapeutic advances have been made over the past several decades. Cytotoxic therapy remains the mainstay of treatment for both advanced esophageal adenocarcinoma and squamous cell carcinoma (SCC), with incremental benefit conferred by antibodies targeting HER2 and VEGFR in selected patients. However, intrinsic or acquired resistance in this disease almost invariably occurs and remains a major challenge. Moreover, although large-scale exome and whole-genome sequencing efforts have identified a variety of somatic mutations and copy number variations, particularly amplifications, in esophageal cancer, the ability to translate these findings successfully into actionable therapeutic approaches has been elusive. More recently, immunotherapeutic strategies, most notably immune checkpoint inhibitors, have demonstrated benefit to a subset of patients with both esophageal adenocarcinoma and SCC and represent an area of active clinical investigation. In this article, we discuss some of the insights derived from past trials of esophageal cancer, highlight ongoing research efforts in this arena, and emphasize the need to refine our approach to treating patients based on distinct anatomic, histologic, and molecular features. Clin Cancer Res; 22(17); 4283-90. (c)2016 AACR. PMID- 27370608 TI - [Not Available]. PMID- 27370605 TI - Identification of Existing Drugs That Effectively Target NTRK1 and ROS1 Rearrangements in Lung Cancer. AB - PURPOSE: Efforts to discover drugs that overcome resistance to targeted therapies in patients with rare oncogenic alterations, such as NTRK1 and ROS1 rearrangements, are complicated by the cost and protracted timeline of drug discovery. EXPERIMENTAL DESIGN: In an effort to identify inhibitors of NTRK1 and ROS1, which are aberrantly activated in some patients with non-small cell lung cancer (NSCLC), we created and screened a library of existing targeted drugs against Ba/F3 cells transformed with these oncogenes. RESULTS: This screen identified the FDA-approved drug cabozantinib as a potent inhibitor of CD74-ROS1 transformed Ba/F3, including the crizotinib-resistant mutants G2032R and L2026M (IC50 = 9, 26, and 11 nmol/L, respectively). Cabozantinib inhibited CD74-ROS1 transformed Ba/F3 cells more potently than brigatinib (wild-type/G2032R/L2026M IC50 = 30/170/200 nmol/L, respectively), entrectinib (IC50 = 6/2,200/3,500 nmol/L), and PF-06463922 (IC50 = 1/270/2 nmol/L). Cabozantinib inhibited ROS1 autophosphorylation and downstream ERK activation in transformed Ba/F3 cells and in patient-derived tumor cell lines. The IGF-1R inhibitor BMS-536924 potently inhibited CD74-NTRK1-transformed compared with parental Ba/F3 cells (IC50 = 19 nmol/L vs. > 470 nmol/L). A patient with metastatic ROS1-rearranged NSCLC with progression on crizotinib was treated with cabozantinib and experienced a partial response. CONCLUSIONS: While acquired resistance to targeted therapies is challenging, this study highlights that existing agents may be repurposed to overcome drug resistance and identifies cabozantinib as a promising treatment of ROS1-rearranged NSCLC after progression on crizotinib. Clin Cancer Res; 23(1); 204-13. (c)2016 AACR. PMID- 27370607 TI - HGF/Met Signaling in Head and Neck Cancer: Impact on the Tumor Microenvironment. AB - Studies to date have revealed several major molecular alterations that contribute to head and neck squamous cell carcinoma (HNSCC) initiation, progression, metastatic spread, and therapeutic failure. The EGFR is the only FDA-approved therapeutic target, yet responses to cetuximab have been limited. Activation and cross-talk of cellular receptors and consequent activation of different signaling pathways contribute to limited activity of blockade of a single pathway. The hepatocyte growth factor (HGF) receptor, Met, has been implicated in HNSCC tumorigenesis and EGFR inhibitor resistance. HGF, the sole ligand of Met, is overexpressed in the tumor microenvironment. The role of HGF/Met signaling in proliferation, metastasis, and angiogenesis has been investigated in HNSCC, leading to clinical trials with various Met inhibitors and HGF antibodies. However, the role of the HGF/Met signaling axis in mediating the tumor microenvironment has been relatively understudied in HNSCC. In this review, we discuss the functional roles of Met and HGF in HNSCC with a focus on the tumor microenvironment and the immune system. Clin Cancer Res; 22(16); 4005-13. (c)2016 AACR. PMID- 27370610 TI - [Not Available]. PMID- 27370609 TI - [Not Available]. PMID- 27370611 TI - [Not Available]. PMID- 27370612 TI - [Not Available]. PMID- 27370613 TI - [Not Available]. PMID- 27370614 TI - [Not Available]. PMID- 27370615 TI - [Not Available]. PMID- 27370617 TI - [Not Available]. PMID- 27370616 TI - [Not Available]. PMID- 27370618 TI - [Not Available]. PMID- 27370619 TI - [Not Available]. PMID- 27370621 TI - [Not Available]. PMID- 27370620 TI - [Not Available]. PMID- 27370622 TI - [Not Available]. PMID- 27370623 TI - [Not Available]. PMID- 27370624 TI - [Not Available]. PMID- 27370626 TI - [Not Available]. PMID- 27370625 TI - [Not Available]. PMID- 27370627 TI - [Not Available]. PMID- 27370628 TI - [Not Available]. PMID- 27370629 TI - [Not Available]. PMID- 27370630 TI - [Not Available]. PMID- 27370631 TI - [Not Available]. PMID- 27370632 TI - [Not Available]. PMID- 27370633 TI - [Not Available]. PMID- 27370634 TI - [Not Available]. PMID- 27370635 TI - [Not Available]. PMID- 27370637 TI - [Not Available]. PMID- 27370639 TI - [Not Available]. PMID- 27370636 TI - Different Types of Urinary Steroid Profiling Obtained by High-Performance Liquid Chromatography and Gas Chromatography-Mass Spectrometry in Patients with Adrenocortical Carcinoma. AB - Urinary steroid profiling (USP) was studied using high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) methods in 108 patients with adrenocortical adenoma (ACA) and in 31 patients with adrenocortical carcinoma (ACC). Thirteen ACC and Cushing's syndrome (ACC-CS) patients had two types of USP as well as 18 ACC patients without hypercortisolism. These four types differed by androgen and glucocorticoid secretion of the adrenal cortex. Fifteen main ACC features were observed by GC MS. Urinary excretion of dehydroepiandrosterone (DHEA) was increased in 67.7 % of ACC patients and tetrahydro-11-deoxycortisol (THS) in 74.2 %. By combination of the following parameters: THS >900 MUg/24 h and/or DHEA >1500 MUg/24 h with ratios of 3alpha,16,20-pregnentriol/3beta,16,20-pregnentriol (3alpha,16,20dP3/3beta,16,20dP3) less than 6.0 and 3alpha,17,20dP3/3beta,17,20dP3 less than 9.0 and the detection of "non-classical" 5-en-pregnens, not found in ACA and healthy persons, 100 % sensitivity and specificity of ACC and ACA differential diagnosis were achieved. Features of 21-hydroxylase and 11beta hydroxylase deficiency were observed by GC-MS in 32.2 and 61.3 % of the ACC patients, respectively. Additional features for ACC-CS diagnostic were increased urinary excretion of 6beta-hydroxycortisol, 18-hydroxycorticosterone, the sum (UFF + UFE) obtained by HPLC, tetrahydrocorticosterone, and the sum (THF + THE + allo-THF) obtained by GC-MS. PMID- 27370638 TI - [Not Available]. PMID- 27370640 TI - [Not Available]. PMID- 27370641 TI - [Not Available]. PMID- 27370642 TI - [Not Available]. PMID- 27370643 TI - Evaluation of cognitive subdomains, 25-hydroxyvitamin D, and 1,25 dihydroxyvitamin D in the European Male Ageing Study. AB - PURPOSE: Although lower levels of vitamin D have been related to poor cognitive functioning and dementia in older adults, evidence from longitudinal investigations is inconsistent. The objective of this study was to determine whether 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels are associated with specified measures of cognitive decline in ageing men. METHODS: The European Male Ageing Study (EMAS) followed 3369 men aged 40-79 over 4.4 years. 25(OH)D levels at baseline were measured by radioimmunoassay, and 1,25(OH)2D levels were obtained with liquid chromatography-tandem mass spectrometry. Visuoconstructional abilities, visual memory, and processing speed at baseline and follow-up were assessed using the Rey-Osterrieth Complex Figure Test (ROCF), Camden Topographical Recognition Memory (CTRM), and the Digit Symbol Substitution Test (DSST). RESULTS: Following attritions, a total of 2430 men with a mean (SD) age of 59.0 (10.6) were included in the analyses. At baseline, the mean 25(OH)D concentration was 64.6 (31.5) nmol/l, and mean 1,25(OH)2D level was 59.6 (16.6) pmol/l. In age-adjusted linear regression models, high 25(OH)D concentrations were associated with a smaller decline in the DSST (beta = 0.007, p = 0.020). Men with low 25(OH)D levels (<50 nmol/l) showed a greater decline in the CTRM compared to men with higher (>=75 nmol/l) levels (beta = -0.41, p = 0.035). However, these associations disappeared after adjusting for confounders such as depressive symptoms, BMI, and comorbidities. There was no indication of a relationship between 1,25(OH)2D and decline in cognitive subdomains. CONCLUSION: We found no evidence for an independent association between 25(OH)D or 1,25(OH)2D levels and visuoconstructional abilities, visual memory, or processing speed over on average 4.4 years in this sample of middle-aged and elderly European men. PMID- 27370645 TI - Decreased expression of microRNA-21 is associated with increased cytokine production in peripheral blood mononuclear cells (PBMCs) of obese type 2 diabetic and non-diabetic subjects. AB - The aim of this study was to investigate the role of miR-21 in inflammatory responses in peripheral blood mononuclear cells (PBMCs) of type 2 diabetic (T2D) and healthy subjects. 20 healthy and 20 T2D subjects were enrolled in the study. miR-21 expression in PBMCs of the subjects was measured using real-time PCR. IL-6 and TNF-alpha levels in culture supernatants were quantified using ELISA. miR-21 expression was not significantly different between the diabetic and nondiabetic groups. A downregulation of miR-21 expression was observed in PBMCs of obese subjects in both diabetic and nondiabetic groups. In addition, miR-21 expression was negatively correlated with weight, waist circumference, body mass index, and triglyceride in both the diabetic and nondiabetic groups. Our results also demonstrated that the PBMCs of obese subjects significantly secreted a higher level of IL-6 and TNF-alpha in comparison with the PBMCs of nonobese subjects. Furthermore, a significant inverse correlation between miR-21 expression and TNF alpha and IL-6 production from the PBMCs was observed. These data suggest that miR-21 expression is decreased in PBMCs of obese subjects and reduced expression appears to be associated with increased secreted cytokine level in media of PBMCs of obese subjects. PMID- 27370644 TI - Sex differences in the regulation of spatially distinct cardiac mitochondrial subpopulations. AB - Spatially distinct mitochondrial subpopulation may mediate myocardial pathology through permeability transition pore opening (MPTP). The goal of this study was to assess sex differences on the two spatially distinct mitochondrial subpopulations: subsarcolemmal mitochondria (SSM) and intermyofibrillar mitochondria (IFM) based on morphology, membrane potential, mitochondrial function, oxidative phosphorylation, and MPTP. Aged matched Wistar rats were used to study SSM and IFM. Mitochondrial size was larger in SSM than in IFM in both genders. However, SSM internal complexity, yield, and membrane potential were higher in male than in female. The maximal rate of mitochondrial respiration, states 3 and 4, using glutamate + malate as substrate, were higher in IFM and SSM in the male group compared to female. The respiratory control ratio (RCR state3/state 4), was not different in both SSM and IFM with glutamate + malate. The ADP:O ratio was found higher in IFM and SSM from female compared to males. When pyruvate was used, state 3 was found unchanged in both IFM and SSM, state 4 was also greater in male IFM compared to female. The RCR increased in the SSM while IFM remained the same. State 4 was higher in male SSM while in the IFM remained the same. The IFM presented a higher Ca(2+) retention capacity compared with SSM, however, there was a greater sensitivity to Ca(2+)-induced MPTP in SSM and IFM in the male group compared to female. In conclusion, our data show that spatially distinct mitochondrial subpopulations have sex-based differences in oxidative phosphorylation, morphology, and calcium retention capacity. PMID- 27370646 TI - Knocking down of p53 triggers apoptosis and autophagy, concomitantly with inhibition of migration on SSC-4 oral squamous carcinoma cells. AB - Oral squamous cell carcinoma (OSCC) is a malignancy with elevated prevalence and somber prognosis due to the fact that most of the patients are diagnosed at an advanced stage. p53 has a crucial role in proliferation and apoptosis during the occurrence and development of numerous malignant tumors. The impact of mutated p53 on the development and progression of OSCC is unclear and might have therapeutic implications. Using an in vitro RNA interference experiment, we have evaluated the impact of p53 knockdown on cell viability, apoptosis, migration, and gene expression for key genes involved in apoptosis and angiogenesis. We observed that inhibiting the expression of p53 decreased the proliferation ability and induced apoptosis/autophagy in SSC-4 cells. Moreover, we observed that this has decreased migration and has blocked the expression of VEGF. In conclusion, our research provides a proof that a direct connection between p53 knockdown and OSCC cell death can be established, therefore opening new potential directions in OSCC molecular therapeutics and management. PMID- 27370647 TI - [Midwives, vaccines and health literacy: an underexplored relationship?]. PMID- 27370648 TI - Quality of care provided to prostate cancer (PC) patients for prevention and treatment of osteoporosis induced by androgen deprivation therapy (ADT). AB - OBJECTIVES: This study aims to evaluate the quality of care (QOC) and use of validated risk algorithms provided in a specialized osteoporosis clinic to men with prostate cancer on androgen deprivation therapy (ADT) who are at risk of bone loss and fragility fractures. PATIENTS AND METHODS: Charts for 100 consecutive men (mean age 73.0 years) on ADT referred to a tertiary osteoporosis clinic in Toronto, Canada between 2010 and 2014 were reviewed. The following QOC issues were examined: (a) bone health services provided, i.e., screening, preventing, and treating osteoporosis; and (b) use of national guidelines and fracture risk assessment tools for targeting appropriate therapy. RESULTS: The median (IQR) duration of ADT was 21.4 (26.9) months at the baseline visit. Nineteen patients had their first bone mineral density test before starting ADT and 34 during the first year of use. At initial consultation, 83 and 30 patients were taking inadequate amounts of calcium and vitamin D, respectively. A validated fracture risk assessment tool was used in all patients; 42 had a moderate 10-year fracture risk and 12 were high risk. Sixteen (72.7 %) of sedentary patients were advised to increase physical activity. Sixty-four (77.1 %) and 28 (93.3 %) of patients not taking appropriate amounts of calcium and vitamin D, respectively, were recommended to adjust their intake to guideline levels. All patients at high fracture risk were recommended a bisphosphonate. CONCLUSIONS: The majority of referred patients had moderate to high fracture risk. The osteoporosis clinic recommended guideline-based bone health care for the vast majority of men on ADT. PMID- 27370649 TI - Is targeted fortification of human breast milk an optimal nutrition strategy for preterm infants? An interventional study. AB - BACKGROUND: Fortifying human milk contributes to the prevention of postnatal growth failure in preterm infants. Because of the natural variability of human milk, targeted fortification of human milk has been advocated. However, data regarding the efficacy and safety of prolonged targeted fortification are scarce. We aimed to assess the safety of targeted fortification of human milk in preterm infants compared with standard fortification, as well as the effects on infant growth. METHODS: We conducted an interventional study during hospital stay in healthy very low birth weight preterm infants who were exclusively fed human milk. Pools of human milk collected for 24 h were analysed using mid-infrared transmission spectroscopy. Targeted fortification of human milk was performed by adding macronutrients to native human milk to obtain optimal ratios of fat (4.4 g), carbohydrates (8.8 g), and protein (3 g) per 100 ml. The intervention period lasted 4-7 weeks. Weekly weight and daily growth rates were compared with those of a standardized fortification group of very low birth weight preterm infants who received standard fortified human milk (n = 10). The osmolality as well as the metabolic and gastrointestinal tolerance were monitored. Intergroup differences were evaluated using the Mann-Whitney U-test. RESULTS: A total of 10 preterm infants (birth weight 1223 +/- 195 g; gestational age 29.1 +/- 1.03 weeks) were enrolled and 118 samples of pooled milk were analysed. On average, 1.4 +/- 0.1 g of protein, 2.3 +/- 0.5 g of carbohydrate, and 0.3 +/- 0.1 g of fat per 100 ml were added to the milk. Osmolality values after target fortification were within recommended limits (376 +/- 66 mOsml/kg). Weekly weight gain (205.5 g; 95 % CI 177-233 vs 155 g; 95 % CI 132-178; p = 0.025) and daily growth rates (15.7 g/kg/day; 95 % CI 14.5-16.9 vs 12.3 g/kg/day; 95 % CI 10.7-13.9; p = 0.005) were higher in infants receiving target fortification than in infants receiving standardized fortification. The infants receiving targeted fortified milk consumed similar volumes as infants in the standardized fortification group (148 +/- 4.5 vs 146 +/- 4 ml/kg/day). No signs of either gastrointestinal or metabolic intolerance were observed. CONCLUSIONS: Target fortification appears to promote growth in very low birth weight preterm infants without any detrimental effects. Trial registration NCT02716337. PMID- 27370651 TI - Subtalar Distraction Arthrodesis with Fresh Frozen Femoral Neck Allograft: A Retrospective Case Series. AB - Subtalar joint distraction arthrodesis has been well reported with use of structural iliac crest or local autologous bone graft for malunited calcaneal fractures. Early reports for structural allograft did not yield good, consistent results, leading to a subsequent lack of recommendation in previous literature. Newer studies have had promising results utilizing femoral allograft as an alternative to autogenous bone graft. We performed a retrospective chart review on 10 patients (12 feet) undergoing subtalar joint distraction arthrodesis with femoral neck allograft for malunited calcaneal fractures. The primary aim of this study was to report on successful union rates and, in addition, outline any consistent complications. Twelve of the 12 procedures (100%) yielded successful fusion with a mean final follow-up of 7.7 months (range = 2.2-35.1 months). The mean increase in talocalcaneal height was 4 mm (range = 2-6 mm). The overall complication rate was 16.6%, including one superficial wound complication that healed uneventfully and one hardware removal. In conclusion, the current study reports a 100% successful fusion rate with interpositional structural femoral neck allograft in treatment for malunited calcaneal fractures. LEVELS OF EVIDENCE: Therapeutic, Level IV: Case series. PMID- 27370650 TI - The antioxidative defense system is involved in the premature senescence in transgenic tobacco (Nicotiana tabacum NC89). AB - BACKGROUND: alpha-Farnesene is a volatile sesquiterpene synthesized by the plant mevalonate (MVA) pathway through the action of alpha-farnesene synthase. The alpha-farnesene synthase 1 (MdAFS1) gene was isolated from apple peel (var. white winter pearmain), and transformed into tobacco (Nicotiana tabacum NC89). The transgenic plants had faster stem elongation during vegetative growth and earlier flowering than wild type (WT). Our studies focused on the transgenic tobacco phenotype. RESULTS: The levels of chlorophyll and soluble protein decreased and a lower seed biomass and reduced net photosynthetic rate (Pn) in transgenic plants. Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) and superoxide radicals (O 2 (.-) ) had higher levels in transgenics compared to controls. Transgenic plants also had enhanced sensitivity to oxidative stress. The transcriptome of 8-week-old plants was studied to detect molecular changes. Differentially expressed unigene analysis showed that ubiquitin-mediated proteolysis, cell growth, and death unigenes were upregulated. Unigenes related to photosynthesis, antioxidant activity, and nitrogen metabolism were downregulated. Combined with the expression analysis of senescence marker genes, these results indicate that senescence started in the leaves of the transgenic plants at the vegetative growth stage. CONCLUSIONS: The antioxidative defense system was compromised and the accumulation of reactive oxygen species (ROS) played an important role in the premature aging of transgenic plants. PMID- 27370652 TI - Idiopathic Toe Walking: Family Predisposition and Gender Distribution. AB - Current literature is inconsistent concerning the causes and the frequency of idiopathic toe walking (ITW). Available studies vary widely in their results. The aim of this study is to supply gender-related data particularly regarding the genetic influence on toe walking. Methods The ITW patterns of 836 children were recorded and analyzed during a period of 4 years. Questionnaires and clinical measurements were evaluated along with clinical tests, assessing the occurrence and severity of toe walking. Information about the incidence of toe-walkers in the family was recorded. Results Of the 836 toe-walkers, 64% were boys and 42% had a positive family history (PF-TW). About 60% of the PF-TW children had fathers with a positive toe-walking pattern. PF-TW children were on average half a year younger than children with a negative family predisposition (NF-TW). Conclusions This study shows that a genetic component might be factor in toe walking. PF-TW children were more severely affected in all performed clinical tests than NF-TW children. LEVELS OF EVIDENCE: Prognostic, Level IV. PMID- 27370654 TI - Staging for Remnant Gastric Cancer: The Metastatic Lymph Node Ratio vs. the UICC 7th Edition System. AB - BACKGROUND: Unlike primary gastric cancer, a remnant gastric cancer (RGC) staging system has not been established. The retrieved lymph node counts (RLN) in RGC is generally lower than that in primary gastric cancer, so it is unclear whether positive lymph node count reflects the RGC patient's survival. Therefore, the lymph node ratio (LR) may be more useful for RGC staging than the 7th edition UICC classification. METHODS: Patients (n = 191) who underwent gastrectomy with curative intent for RGC participated in this study. LR was classified as LR = 0, 0 < LR <= 0.1, 0.1 < LR <= 0.4, and 0.4 < LR. Modified TNM staging (mTNM-LR) was established by combining the pT (7th UICC) with LR. The predictive accuracy of LR and mTNM-LR was compared with that of the pN (7th UICC) and TNM (7th UICC), respectively. RESULTS: The mean RLN was 14.4 and that of 128 patients (67 %) was <=15. Fifty-one patients (27 %) had metastatic lymph nodes. Multivariable analyses revealed that pT (7th UICC) (p < 0.001) and pN (7th UICC) (p = 0.001), but not LR, were independent risk factors for overall survival. The overall c index (95 % confidence interval) of each staging system was as follows: pN (7th UICC): 0.700 (0.627-0.771); LR: 0.701 (0.627-0.775), TNM (7th UICC): 0.808 (0.761 0.870); mTNM-LR: 0.807 (0.737-0.871). There were no significant differences in the predictive accuracy between pN (7th UICC) and LR, and TNM (7th UICC) and mTNM LR. CONCLUSIONS: LR was not superior to pN (7th UICC). Thus, the 7th edition UICC classification is a practical and reliable staging system for RGC. PMID- 27370653 TI - Systematic Review of Resection Rates and Clinical Outcomes After FOLFIRINOX-Based Treatment in Patients with Locally Advanced Pancreatic Cancer. AB - BACKGROUND: FOLFIRINOX prolongs survival in patients with metastatic pancreatic cancer and may also benefit patients with locally advanced pancreatic cancer (LAPC). Furthermore, it may downstage a proportion of LAPC into (borderline) resectable disease, however data are lacking. This review assessed outcomes after FOLFIRINOX-based therapy in LAPC. METHODS: The PubMed, EMBASE and Cochrane library databases were systematically searched for studies published to 31 August 2015. Primary outcome was the (R0) resection rate. RESULTS: Fourteen studies involving 365 patients with LAPC were included; three studies administered a modified FOLFIRINOX regimen. Of all patients, 57 % (n = 208) received radiotherapy. The pooled resection rate was 28 % (n = 103, 77 % R0), with a perioperative mortality of 3 % (n = 2), and median overall survival ranged from 8.9 to 25.0 months. Survival data after resection were scarce, with only one study reporting a median overall survival of 24.9 months in 28 patients. A complete pathologic response was found in 6 of 85 (7 %) resected specimens. Dose reductions were described in up to 65 % of patients, grade 3-4 toxicity occurred in 23 % (n = 51) of patients, and 2 % (n = 5) had to discontinue treatment. Data of patients treated solely with FOLFIRINOX, without additional radiotherapy, were available from 292 patients: resection rate was 12 % (n = 29, 70 % R0), with 15.7 months median overall survival and 19 % (n = 34) grade 3-4 toxicity. CONCLUSIONS: Outcomes after FOLFIRINOX-based therapy in patients with LAPC seem very promising but further prospective studies are needed, especially with regard to survival after resection. PMID- 27370656 TI - [Not Available]. PMID- 27370655 TI - [Not Available]. PMID- 27370657 TI - [Not Available]. PMID- 27370659 TI - [Not Available]. PMID- 27370658 TI - [Not Available]. PMID- 27370660 TI - [Not Available]. PMID- 27370661 TI - [Not Available]. PMID- 27370662 TI - [Not Available]. PMID- 27370663 TI - [Not Available]. PMID- 27370664 TI - [Not Available]. PMID- 27370665 TI - [Not Available]. PMID- 27370666 TI - [Not Available]. PMID- 27370668 TI - [Not Available]. PMID- 27370667 TI - [Not Available]. PMID- 27370669 TI - [Not Available]. PMID- 27370670 TI - [Not Available]. PMID- 27370672 TI - [Not Available]. PMID- 27370671 TI - [Not Available]. PMID- 27370673 TI - [Not Available]. PMID- 27370674 TI - [Not Available]. PMID- 27370676 TI - [Not Available]. PMID- 27370675 TI - [Not Available]. PMID- 27370677 TI - [Not Available]. PMID- 27370678 TI - [Not Available]. PMID- 27370679 TI - [Not Available]. PMID- 27370680 TI - [Not Available]. PMID- 27370681 TI - Parental Meta-Emotion Philosophy and Emotion Coaching in Families of Children and Adolescents with an Anxiety Disorder. AB - Using a multi-method approach, this study examined differences in parental meta emotional philosophy (including, parental emotional awareness and emotion coaching) for families with anxiety disordered (AD; n = 74) and non-AD (n = 35) children (aged 7 to 15). Further, it was investigated whether children's emotion regulation (ER) varied across the AD and non-AD groups. Parent(s) were interviewed about their awareness of emotions and emotion coaching; completed a battery of questionnaires that included a measure assessing children's emotion regulation; and engaged in a parent-child discussion task. Results indicated that compared to parents of non-AD youth, parents of AD youth were less aware of their own emotions and their children's emotions, and these results varied by emotion type. Parents of AD youth engaged in significantly less emotion coaching than parents of non-AD youth. AD youth were identified as having significantly greater difficulty regulating their emotions when compared to non-AD youth. Implications for the role of parental meta-emotional philosophy and AD youth's emotion regulation are discussed. PMID- 27370682 TI - Post-procedural pseudoaneurysms: Single-center experience. AB - Objectives Pseudoaneurysms are a well-recognized complication of percutaneous angiographic procedures. Ultrasound-guided thrombin injection is currently the preferred treatment modality. This study was undertaken to evaluate our experience with the management of post-procedure pseudoaneurysms. Methods A retrospective study was undertaken of all patients who developed a post-procedure pseudoaneurysm between March 2004 and January 2013. Data were obtained from our prospectively maintained non-invasive vascular laboratory data base. Results Overall, 167 patients (80 men) with post-procedure pseudoaneurysms were identified. The mean age was 66 years. Post-procedure pseudoaneurysms developed following diagnostic coronary angiography (38%), coronary angioplasty (37%), peripheral vascular interventions (14.7%), or other access procedures (7.6%). Mean post-procedure pseudoaneurysm diameter was 2.8 +/- 1.8 cm. One hundred forty two post-procedure pseudoaneurysms were injected with thrombin under ultrasound guidance. Primary success rate was 93.5%. There were 12 (8.5%) procedural failures of which seven (58%) responded to reinjection, three (25%) required operative management, one was treated with ultrasound-guided compression, and one (8.3%) was simply observed. On multivariate analysis, failures were associated with increased aneurysm diameter ( p = 0.006; odds ratio 2.23, 95% CI 1.25 to 3.96), end-stage renal disease ( p = 0.013; odds ratio 1.15, 95% CI 1.09 to 1.78) and superficial femoral artery aneurysm origin ( p = 0.031; odds ratio 0.20, 95% CI 0.04 to 0.86). There were two episodes of thrombus formation in the femoral artery; one resolved with anticoagulation alone, and the other required thrombectomy. Conclusions Percutaneous ultrasound-guided thrombin injection is an effective and safe method for managing post-procedure pseudoaneurysms. Failure rates are low and associated with large aneurysm size, superficial femoral artery origin and end-stage renal disease. PMID- 27370683 TI - Debate: adjuvant whole brain radiotherapy or not? More data is the wiser choice. AB - Every year 170,000 patients are diagnosed with brain metastases (BMs) in the United States. Traditionally, adjuvant whole brain radiotherapy (AWBRT) has been offered following local therapy with neurosurgery (NSx) and/or stereotactic radiosurgery (SRS) to BMs. The aim is to increase intracranial control, thereby decreasing symptoms from intracranial progression and a neurological death. There is a rapidly evolving change in the radiation treatment of BMs happening around the world. AWBRT is now being passed over in favour of repeat scanning at regular intervals and more local therapies as more BMs appear radiologically, BMs that may never become symptomatic. This change has happened after the American Society for Radiation Oncology (ASTRO) in Item 5 of its "Choosing Wisely 2014" list recommended: "Don't routinely add adjuvant whole brain radiation therapy to SRS for limited brain metastases". The guidelines are supposed to be based on the highest evidence to hand at the time. This article debates that the randomised controlled trials (RCTs) published prior to this recommendation consistently showed AWBRT significantly increases intracranial control, and avoids a neurological death, what it is meant to do. It also points out that, despite the enormity of the problem, only 774 patients in total had been randomised over more than three decades. These trials were heterogeneous in many respects. This data can, at best, be regarded as preliminary. In particular, there are no single histology AWBRT trials yet completed. A phase two trial investigating hippocampal avoiding AWBRT (HAWBRT) showed significantly less NCF decline compared to historical controls. We now need more randomised data to confirm the benefit of adjuvant HAWBRT. However, the ASTRO Guideline has particularly impacted accrual to trials investigating this, especially the international ANZMTG 01.07 WBRTMel trial. This is an RCT investigating AWBRT following local treatment in patients with one to three BMs from melanoma. WBRTMel has accrued 196 of a required 220 to date but accrual has slowed. HAWBRT may now never be tested in a randomised setting. Encouraging more data in AWBRT is the wiser choice. PMID- 27370684 TI - HLA-A, -B, -C, -DRB1 and -DQB1 alleles and haplotypes in 951 Southeast Asia Malays from Peninsular Malaysia. AB - A total of 951 Southeast Asia Malays from Peninsular Malaysia were genotyped for HLA-A, -B, -C -DRB1, and -DQB1 loci using polymerase chain reaction sequence specific oligonucleotide probe hybridization methods. In this report, there were significant deviation from Hardy-Weinberg proportions for the HLA-A (p<0.0001), B (p<0.0001), -DRB1 (p<0.0001) and -DQB1 (p<0.01) loci. Minor deviations from HWEP were detected for HLA-C (p=0.01). This genotype data was available in Allele Frequencies Network Database (AFND) Gonzalez-Galarza et al. (2015). PMID- 27370685 TI - Association of genetic variants in the 3'UTR of HLA-G with Recurrent Pregnancy Loss. AB - Human Leukocyte Antigen (HLA)-G is involved in reprogramming immune responses at fetal-maternal interface during pregnancy. We evaluated the genetic diversity of the 3' Un-Translated Region (UTR) of HLA-G, previously associated with HLA-G mRNA post-transcriptional regulation, in women with unexplained Recurrent Pregnancy Loss (RPL), with 2 pregnancy losses (RPL-2, n=28), or 3 or more pregnancy losses (RPL-3, n=24), and in 30 women with a history of successful pregnancy. Results showed in RPL-2, but not in RPL-3, women compared to controls: i) higher frequency of the 14bp Ins allele, in single and in double copy; ii) significantly lower frequency of DelG/X genotype, iii) reduced frequency of the UTR-2, and UTR 3 haplotypes; iv) higher frequencies of the UTR-5, UTR-7, and UTR-8 haplotypes. This pilot study supports the relevance of performing 3'UTR HLA-G genetic screening, not limited to a specific polymorphism, but considering the extended haplotypes, as a possible predictor of pregnancy outcome. PMID- 27370686 TI - Self-paired monoclonal antibody lateral flow immunoassay strip for rapid detection of Acidovorax avenae subsp. citrulli. AB - We screened a highly specific monoclonal antibody (McAb), named 6D, against Acidovorax avenae subsp. citrulli (Aac). Single McAb 6D was used as both nanogold labeled antibody and test antibody to develop a single self-paired colloidal gold immunochromatographic test strip (Sa-GICS). The detection limit achieved using the Sa-GICS approach was 10(5) CFU/mL, with a result that can be observed by the naked eye within 10 min. Moreover, Sa-GICS can detect eight strains of Aac and display no cross-reactions with other pathogenic plant microorganisms. Artificial contamination experiments demonstrated that Sa-GICS would not be affected by impurities in the leaves or stems of the plants and were consistent with the PCR results. This is the first report on the development of a colloidal gold immunoassay strip with self-paired single McAb for the rapid detection of Aac. Graphical Abstract Schematic representation of the test strip. PMID- 27370687 TI - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the human biomonitoring of non-occupational exposure to the fragrance 2-(4-tert butylbenzyl)propionaldehyde (lysmeral). AB - 2-(4-tert-Butylbenzyl)propionaldehyde also known as lysmeral, lilial, or lily aldehyde (CAS No. 80-54-6) is a synthetic odorant mainly used as a fragrance in a variety of consumer products like cleaning agents, fine fragrances, cosmetics, and air fresheners. Due to its broad application in various fields, lysmeral was selected for the development of a biomonitoring method for the quantitative exposure assessment within the frame of the cooperation project of the Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (BMUB) and the German Chemical Industry Association (VCI). A method based on ultra-high pressure liquid chromatography combined with tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of potential biomarkers of lysmeral in human urine samples. Sample cleanup was performed by liquid-liquid extraction (LLE). Quantification was achieved by standard addition using stable isotope-labeled, authentic reference standards. The method is characterized by its robustness, reliability, and excellent sensitivity as proven during method validation according to approved standard guidelines. The following five lysmeral metabolites were identified as potential biomarkers of exposure for lysmeral in human urine samples: lysmerol, lysmerylic acid, hydroxylated lysmerylic acid, tert-butylbenzoic acid (TBBA), and tert-butylhippuric acid (TBHA). The determination of lysmerol required derivatization with 3 nitrophthalic acid anhydride and showed the lowest limit of detection (LOD) and limit of quantification (LOQ) in urine (0.035 and 0.10 MUg/L, respectively). LOD and LOQ for the other metabolites were in the range of 0.12-0.15 and 0.36-0.45 MUg/L, respectively. Accuracy for all analytes was in the range of 90-110 %. Intra- and inter-day precision was in the range of 5-10 %, except for TBHA, for which the coefficient of variation was unacceptably high (>20 %) and therefore excluded from the method. The method was applied to urine samples of 40 adult volunteers. The four remaining lysmeral metabolites were detectable in most of the 40 urine samples in the following order according to quantity excreted: TBBA >> lysmerol ~ lysmerylic acid > hydroxy-lysmerylic acid. In conclusion, we successfully developed a biomonitoring method for the assessment of the exposure to lysmeral in the general population. The method is characterized by its precision, robustness, and accuracy. The metabolites lysmerol, lysmerylic acid, hydroxylated lysmerylic acid, and TBBA turned out to be suitable biomarkers of exposure to lysmeral, either alone or in combination with one or more of the other metabolites. Sensitivity was found to be sufficient for assessing the background exposure to this chemical in the general population. PMID- 27370689 TI - IR-MALDI ion mobility spectrometry. AB - The novel combination of infrared matrix-assisted laser dispersion and ionization (IR-MALDI) with ion mobility (IM) spectrometry makes it possible to investigate biomolecules in their natural environment, liquid water. As an alternative to an ESI source, the IR-MALDI source was implemented in an in-house-developed ion mobility (IM) spectrometer. The release of ions directly from an aqueous solution is based on a phase explosion, induced by the absorption of an IR laser pulse (lambda = 2.94 MUm, 6 ns pulse width), which disperses the liquid as nano- and micro-droplets. The prerequisites for the application of IR-MALDI-IM spectrometry as an analytical method are narrow analyte ion signal peaks for a high spectrometer resolution. This can only be achieved by improving the desolvation of ions. One way to full desolvation is to give the cluster ions sufficient time to desolvate. Two methods for achieving this are studied: the implementation of an additional drift tube, as in ESI-IM-spectrometry, and the delayed extraction of the ions. As a result of this optimization procedure, limits of detection between 5 nM and 2.5 MUM as well as linear dynamic ranges of 2-3 orders of magnitude were obtained for a number of substances. The ability of this method to analyze simple mixtures is illustrated by the separation of two different surfactant mixtures. PMID- 27370688 TI - Evaluation of coverage, retention patterns, and selectivity of seven liquid chromatographic methods for metabolomics. AB - Liquid chromatography-mass spectrometry-based metabolomics studies require highly selective and efficient chromatographic techniques. Typically employed reversed phase (RP) methods fail to target polar metabolites, but the introduction of hydrophilic interaction liquid chromatography (HILIC) is slow due to perceived issues of reproducibility and ruggedness and a limited understanding of the complex retention mechanisms. In this study, we present a comparison of the chromatographic performance of a traditional RP-C18 column with zwitterionic, amide-, alkyl diol-, and aminoalkyl-based HILIC and mixed-mode columns. Our metabolite library represents one of the largest analyte sets available and consists of 764 authentic metabolite standards, including amino acids, nucleotides, sugars, and other metabolites, representing all major biological pathways and commonly observed exogenous metabolites (drugs). The coverage, retention patterns, and selectivity of the individual methods are highly diverse even between conceptually related HILIC methods. Furthermore, we show that HILIC sorbents having highly orthogonal selectivity and specificity enhance the coverage of major metabolite groups in (semi-) targeted applications compared to RP. Finally, we discuss issues encountered in the analysis of biological samples based on the results obtained with human plasma extracts. Our results demonstrate that fast and highly reproducible separations on zwitterionic columns are feasible, but knowledge of analyte properties is essential to avoid chromatographic bias and exclusion of key analytes in metabolomics studies. Graphical Abstract The chromatographic parameters of 764 authentic metabolite standards provide the basis for a comparison of coverage, selectivity and orthogonality of 7 reversed-phase (RP), mixed-mode (MM) and hydrophilic interaction liquid chromatography (HILIC) methods. PMID- 27370690 TI - [Not Available]. PMID- 27370691 TI - [Not Available]. PMID- 27370692 TI - [Not Available]. PMID- 27370693 TI - [Not Available]. PMID- 27370694 TI - [Not Available]. PMID- 27370695 TI - [Not Available]. PMID- 27370696 TI - Identification of a Delta12 fatty acid desaturase from oil palm (Elaeis guineensis Jacq.) involved in the biosynthesis of linoleic acid by heterologous expression in Saccharomyces cerevisiae. AB - Oil palm (Elaeis guineensis Jacq.) is one of the highest oil-yield crops in the world. A Delta12-desaturases associated with the primary steps of long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis were successfully cloned from oil palm and their functions identified. The open reading frames (ORFs) of egFAD2 (GenBank accession: KT023602) consisted of 1176bp and code for 391 amino acids. Their deduced polypeptides showed 75-93% identity to microsomal Delta12 desaturases from other higher plants, and each contained the three histidine clusters typical of the catalytic domains of such enzymes. RT-PCR experiment indicated that the egFAD2 gene exhibited the highest accumulation in the mesocarp of fruits at 120-140 DAP (i.e. the fourth period of fruit development) and, despite having different expression levels, the other four stages were at significantly lower levels compared with the fourth stage. Plasmid pYES2-egFAD2 was transformed into Saccharomyces cerevisiae strain INVSc1 using lithium acetate method for expression under the induction of galactose. Yeast cells transformed with plasmid constructs containing egFAD12 produced an appreciable amount of linoleic acids (18:2(Delta9,)(12)), not normally present in wild-type yeast cells, indicating that the genes encoded functional Delta12-desaturase enzymes. PMID- 27370697 TI - Comparison of plasma and tissue samples in epidermal growth factor receptor mutation by ARMS in advanced non-small cell lung cancer. AB - OBJECTIVE: The aim of this study was to assess the effectiveness and accuracy of blood-based circulating-free tumor DNA on testing epidermal growth factor receptor (EGFR) gene mutations. METHODS: In total, 219 non-small cell lung cancer patients in stages III-IV were enrolled into this study. All patients had tissue samples and matched plasma DNA samples. EGFR gene mutations were detected by the Amplification Refractory Mutation System (ARMS). We compared the mutations in tumor tissue samples with matched plasma samples and determined the correlation between EGFR mutation status and clinical pathologic characteristics. RESULT: The overall concordance rate of EGFR mutation status between the 219 matched plasma and tissue samples was 82% (179/219). The sensitivity and specificity for the ARMS EGFR mutation test in the plasma compared with tumor tissue were 60% (54/90) and 97% (125/129), respectively. The positive predictive value was 93% (54/58) and the negative predictive value was 78% (125/161). The median overall survival was longer for those with EGFR mutations than for those without EGFR mutations both in tissue samples (23.98 vs. 12.16months; P<0.001) and in plasma (19.96 vs. 13.63months; P=0.009). For the 68 patients treated with EGFR- tyrosine kinase inhibitors (TKIs), the median progression-free survival (PFS) was significantly prolonged in the EGFR mutant group compared to the non-mutation group in tumor tissue samples (12.26months vs. 2.40months, P<0.001). In plasma samples, the PFS of the mutant group was longer than that of the non-mutant group. However, there was no significant difference between the two groups (10.88months vs. 9.89months, P=0.411). CONCLUSIONS: The detection of EGFR mutations in plasma using ARMS is relatively sensitive and highly specific. However, EGFR mutation status tested by ARMS in plasma cannot replace a tumor tissue biopsy. Positive EGFR mutation results detected in plasma are fairly reliable, but negative results are hampered by a high rate of false negatives. PMID- 27370699 TI - Completeness of primary intracranial tumour recording in the Scottish Cancer Registry 2011-2012. PMID- 27370698 TI - Properties of a monopivot centrifugal blood pump manufactured by 3D printing. AB - An impeller the same geometry as the impeller of a commercial monopivot cardiopulmonary bypass pump was manufactured using 3D printing. The 3D-printed impeller was integrated into the pump casing of the commercially available pump to form a 3D-printed pump model. The surface roughness of the impeller, the hydraulic performance, the axial displacement of the rotating impeller, and the hemolytic properties of the 3D-printed model were measured and compared with those of the commercially available model. Although the surface roughness of the 3D-printed model was significantly larger than that of the commercially available model, the hydraulic performance of the two models almost coincided. The hemolysis level of the 3D-printed model roughly coincided with that of the commercially available model under low-pressure head conditions, but increased greatly under high-pressure head conditions, as a result of the narrow gap between the rotating impeller and the pump casing. The gap became narrow under high-pressure head conditions, because the axial thrust applied to the impeller increased with increasing impeller rotational speed. Moreover, the axial displacement of the rotating impeller was twice that of the commercially available model, confirming that the elastic deformation of the 3D-printed impeller was larger than that of the commercially available impeller. These results suggest that trial models manufactured by 3D printing can reproduce the hydraulic performance of the commercial product. However, both the surface roughness and the deformation of the trial models must be considered to precisely evaluate the hemolytic properties of the model. PMID- 27370701 TI - Nutrition education for early childhood managers, teachers and nursery cooks: a prerequisite for effective obesity prevention. PMID- 27370700 TI - Increasing the frequency of physical activity very brief advice by nurses to cancer patients. A mixed methods feasibility study of a training intervention. AB - OBJECTIVES: To examine the impact, acceptability, practicability and implementation of a training intervention, designed using the Behaviour Change Wheel, on the delivery of very brief advice on physical activity, by nurses to cancer patients. STUDY DESIGN: A mixed methods feasibility study. METHOD: A purposeful sample of nurses (n = 62) were recruited across two delivery arms, face-to-face (n = 55) and online (n = 7). Frequency of delivery of physical activity advice was collected at baseline with follow-up at 12 weeks. The 'capability, opportunity and motivation' of nurses to deliver very brief advice was measured via questionnaire. Semi-structured phone interviews (n = 14) were completed and analyzed thematically. A cost consequence analysis was undertaken. RESULTS: The intervention improved the 'capability, opportunity and motivation' of nurses resulting in a change in knowledge, attitudes and beliefs towards physical activity. The intervention was both acceptable and practical. Face-to face was the preferred mode of delivery, however there was also value in the online option. The cost of delivery per participant was L33.87 for face-to-face delivery, and L103.83 for online delivery inflated due to low recruitment numbers. A significant improvement was seen in delivery of very brief advice at 12 weeks (Z = -4.39, P <= 0.01). CONCLUSION: The intervention is acceptable, practical and improves delivery of very brief advice on physical activity by nurses to cancer patients in the short-term. Both face-to-face and online delivery should be considered. PMID- 27370703 TI - [Not Available]. PMID- 27370702 TI - [Not Available]. PMID- 27370704 TI - [Not Available]. PMID- 27370706 TI - [Not Available]. PMID- 27370705 TI - [Not Available]. PMID- 27370707 TI - [Not Available]. PMID- 27370708 TI - [Not Available]. PMID- 27370709 TI - Heteroprotein complex coacervation: A generic process. AB - Proteins exhibit a rich diversity of functional, physico-chemical and biodegradable properties which makes them appealing for various applications in the food and non-food sectors. Such properties are attributed to their ability to interact and assemble into a diversity of supramolecular structures. The present review addresses the updated research progress in the recent field of complex coacervation made from mixtures of oppositely charged proteins (i.e. heteroprotein systems). First, we describe briefly the main proteins used for heteroprotein coacervation. Then, through some selected examples, we illustrate the particularity and specificity of each heteroprotein system and the requirements that drive optimal assembly into coacervates. Finally, possible and promising applications of heteroprotein coacervates are mentioned. PMID- 27370710 TI - Elevated plasma dihydroorotate in Miller syndrome: Biochemical, diagnostic and clinical implications, and treatment with uridine. AB - BACKGROUND: Miller syndrome (post-axial acrofacial dysostosis) arises from gene mutations for the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH). Nonetheless, despite demonstrated loss of enzyme activity dihydroorotate (DHO) has not been shown to accumulate, but paradoxically urine orotate has been reported to be raised, confusing the metabolic diagnosis. METHODS: We analysed plasma and urine from a 4-year-old male Miller syndrome patient. DHODH mutations were determined by PCR and Sanger sequencing. Analysis of DHO and orotic acid (OA) in urine, plasma and blood-spot cards was performed using liquid chromatography-tandem mass spectrometry. In vitro stability of DHO in distilled water and control urine was assessed for up to 60h. The patient received a 3 month trial of oral uridine for behavioural problems. RESULTS: The patient had early liver complications that are atypical of Miller syndrome. DHODH genotyping demonstrated compound-heterozygosity for frameshift and missense mutations. DHO was grossly raised in urine and plasma, and was detectable in dried spots of blood and plasma. OA was raised in urine but undetectable in plasma. DHO did not spontaneously degrade to OA. Uridine therapy did not appear to resolve behavioural problems during treatment, but it lowered plasma DHO. CONCLUSION: This case with grossly raised plasma DHO represents the first biochemical confirmation of functional DHODH deficiency. DHO was also easily detectable in dried plasma and blood spots. We concluded that DHO oxidation to OA must occur enzymatically during renal secretion. This case resolved the biochemical conundrum in previous reports of Miller syndrome patients, and opened the possibility of rapid biochemical screening. PMID- 27370711 TI - Baby Steps - An Online Program Promoting the Well-Being of New Mothers and Fathers: A Study Protocol. AB - BACKGROUND: Parental well-being can be seriously impacted during the challenging perinatal period. Most research and support services focus on perinatal psychopathology, leaving a need for programs that recognize and enhance the strengths and well-being of parents. Furthermore, fathers have received minimal attention and support relative to mothers, despite experiencing perinatal distress. New parents have limited time and energy to invest in program attendance, and web-based programs provide an ideal platform for delivering perinatal well-being programs. Such programs are globally accessible, available at any time, and can be accessed anywhere with an Internet connection. OBJECTIVE: This paper describes the protocol of a randomized controlled trial investigating the effects on first-time parents' perinatal well-being, comparing two versions of the online program Baby Steps. METHODS: The clinical trial will randomize 240 primiparous mother-father couples to either (1) Babycare, an online information only program providing tips on selected childcare issues, or (2) Well-being, an online interactive program including all content from the Babycare program, plus parental well-being-focused content with tools for goal-setting and problem solving. Both programs will be supported by short message service (SMS) texts at two, four, seven, and ten weeks to encourage continued use of the program. Primary outcomes will be measures of perinatal distress and quality of life. Secondary outcomes will be couple relationship satisfaction, parent self efficacy, and social support. Cost-effectiveness will also be measured for each Baby Steps program. RESULTS: Participant recruitment commenced March, 2015 and continued until October, 2015. Follow-up data collection has commenced and will be completed May, 2016 with results expected in July, 2016. CONCLUSIONS: Perinatal distress has substantial impacts on parents and their infants, with potential to affect later childhood adjustment, relationships, and development. This study aims to test the impact of a highly accessible online program to support parental coping, and maximize the well-being of both parents. By including fathers in the program, Baby Steps has the potential to engage and support this often neglected group who can make a substantial contribution to familial well-being. CLINICALTRIAL: Australian & New Zealand Clinical Trials Registry: ANZCTR12614001256662; https://www.anzctr.org.au/ Trial/Registration/TrialReview.aspx?id=367277 (Archived by WebCite at http://www.webcitation.org/6ibUsjFIL). PMID- 27370712 TI - The polymorphic hMSH5 C85T allele augments radiotherapy-induced spermatogenic impairment. AB - The hMSH5 C85T polymorphism (encoding hMSH5 P29S) is associated with male infertility and radiation-induced apoptotic response. To date, however, the potential association of hMSH5 C85T polymorphism with DNA damage accumulation in spermatozoa of cancer patients treated with radiotherapy is largely unknown. We investigated hMSH5 C85T allele and genotype frequencies, routine semen analysis and sperm DNA Fragmentation Index (DFI) in 113 testicular germ cell tumor (TGCT) patients before and after radiotherapy. The hMSH5 C85T allele is not associated with the occurrence of TGCT. However, in comparison with the CC genotype, TGCT patients with the CT + TT genotypes showed significantly altered sperm counts, sperm morphology and DFI after radiotherapy. Finally, the results of the DSB repair assay demonstrated that hMSH5 P29S could enhance radiotherapy-induced DNA damage by unleashing error-prone non-homologous end joining. Together, our studies indicate that the hMSH5 C85T variation could have an impact on the severity of radiotherapy-provoked long-term side effects through compromising the repair of radiation-induced DNA lesions. PMID- 27370715 TI - [Not Available]. PMID- 27370714 TI - [Not Available]. PMID- 27370716 TI - [Not Available]. PMID- 27370717 TI - [Not Available]. PMID- 27370718 TI - [Not Available]. PMID- 27370719 TI - [Not Available]. PMID- 27370713 TI - Mouse models of Hirschsprung disease and other developmental disorders of the enteric nervous system: Old and new players. AB - Hirschsprung disease (HSCR, intestinal aganglionosis) is a multigenic disorder with variable penetrance and severity that has a general population incidence of 1/5000 live births. Studies using animal models have contributed to our understanding of the developmental origins of HSCR and the genetic complexity of this disease. This review summarizes recent progress in understanding control of enteric nervous system (ENS) development through analyses in mouse models. An overview of signaling pathways that have long been known to control the migration, proliferation and differentiation of enteric neural progenitors into and along the developing gut is provided as a framework for the latest information on factors that influence enteric ganglia formation and maintenance. Newly identified genes and additional factors beyond discrete genes that contribute to ENS pathology including regulatory sequences, miRNAs and environmental factors are also introduced. Finally, because HSCR has become a paradigm for complex oligogenic diseases with non-Mendelian inheritance, the importance of gene interactions, modifier genes, and initial studies on genetic background effects are outlined. PMID- 27370720 TI - [Not Available]. PMID- 27370721 TI - [Not Available]. PMID- 27370722 TI - [Not Available]. PMID- 27370723 TI - [Not Available]. PMID- 27370725 TI - [Not Available]. PMID- 27370724 TI - [Not Available]. PMID- 27370726 TI - [Not Available]. PMID- 27370727 TI - [Not Available]. PMID- 27370729 TI - [Not Available]. PMID- 27370728 TI - [Not Available]. PMID- 27370730 TI - [Not Available]. PMID- 27370731 TI - [Not Available]. PMID- 27370732 TI - [Not Available]. PMID- 27370733 TI - [Not Available]. PMID- 27370734 TI - [Not Available]. PMID- 27370735 TI - [Not Available]. PMID- 27370737 TI - [Not Available]. PMID- 27370736 TI - [Not Available]. PMID- 27370738 TI - [Not Available]. PMID- 27370739 TI - [Not Available]. PMID- 27370740 TI - [Not Available]. PMID- 27370741 TI - [Not Available]. PMID- 27370742 TI - [Not Available]. PMID- 27370743 TI - [Not Available]. PMID- 27370744 TI - Quality-of-Life Impairments Persist Six Months After Treatment of Graves' Hyperthyroidism and Toxic Nodular Goiter: A Prospective Cohort Study. AB - BACKGROUND: The treatment of hyperthyroidism is aimed at improving health-related quality of life (HRQoL) and reducing morbidity and mortality. However, few studies have used validated questionnaires to assess HRQoL prospectively in such patients. The purpose of this study was to assess the impact of hyperthyroidism and its treatment on HRQoL using validated disease-specific and generic questionnaires. METHODS: This prospective cohort study enrolled 88 patients with Graves' hyperthyroidism and 68 with toxic nodular goiter from endocrine outpatient clinics at two Danish university hospitals. The patients were treated with antithyroid drugs, radioactive iodine, or surgery. Disease-specific and generic HRQoL were assessed using the thyroid-related patient-reported outcome (ThyPRO) and the Medical Outcomes Study 36-item Short Form (SF-36), respectively, evaluated at baseline and six-month follow-up. The scores were compared with those from two general population samples who completed ThyPRO (n = 739) and SF 36 (n = 6638). RESULTS: Baseline scores for patients with Graves' hyperthyroidism and toxic nodular goiter were significantly worse than those for the general population scores on all comparable ThyPRO scales and all SF-36 scales and component summaries. ThyPRO scores improved significantly with treatment on all scales in Graves' hyperthyroidism and four scales in toxic nodular goiter, while SF-36 scores improved on five scales and both component summaries in Graves' hyperthyroidism and only one scale in toxic nodular goiter. In Graves' hyperthyroidism, large treatment effects were observed on three ThyPRO scales (Hyperthyroid Symptoms, Tiredness, Overall HRQoL) and moderate effects on three scales (Anxiety, Emotional Susceptibility, Impaired Daily Life), while moderate effects were seen in two ThyPRO scales in toxic nodular goiter (Anxiety, Overall HRQoL). However, significant disease-specific and generic HRQoL deficits persisted on multiple domains across both patient groups. CONCLUSIONS: Graves' hyperthyroidism and toxic nodular goiter cause severe disease-specific and generic HRQoL impairments, and HRQoL deficits persist in both patient groups six months after treatment. These data have the potential to improve communication between physicians and patients by offering realistic estimates of expected HRQoL impairments and treatment effects. Future studies should identify risk factors for persistent HRQoL deficits, compare HRQoL effects of the various therapies, and thereby aid in determining the optimal treatment strategies. PMID- 27370745 TI - Potassium fulvate as co-interpenetrating agent during graft polymerization of acrylic acid from cellulose. AB - Grafting polymerization of acrylic acid onto cellulose in presence of potassium fulvate (KF) as a co-interpenetrating agent results enhanced water sorption compared to materials prepared similarly in its absence. The insertion of potassium fulvate (KF) did not affect the grafting process and is thought to proceed in parallel to the graft polymerization via intensive polycondensation reactions of its function groups (-COOH and OH) with COOH of the monomer and OH groups of cellulose. The combination of graft copolymerization and polycondensation reactions is assumed to produce interpenetrating network structure. Fourier transform infrared (FTIR) confirmed successful incorporation within the network structure which is an evidence for formation of interpenetrating network. The obtained structures showed homogeneous uniform surface as revealed by scanning electron microscopy (SEM). The obtained superabsorbent possessed high water absorbency 422 and 48.8g/g in distilled water and saline (0.9wt.% NaCl solution), respectively, and enhanced water retention even at elevated temperatures as revealed by thermogravimetric analysis (TGA). This could be explained by the high content of hydrophilic groups. The new superabsorbents proved to be efficient devices for controlled release of fertilizers which expands their use in agricultural applications. PMID- 27370746 TI - Extraction, antioxidant and antibacterial activities of Broussonetia papyrifera fruits polysaccharides. AB - Polysaccharides were extracted from Broussonetia papyrifera ((L.) L'Herit. ex Vent.) fruits (BPP), and response surface methodology was used to maximize extraction yield. The optimum extraction conditions were: ratio of water to solid, 30mL/g; extraction duration, 50min; extraction power, 180W; and extraction temperature, 60 degrees C. Under these conditions, the yield of BPP was 8.61%. Then, BPP was purified, and three purified fractions (designated BPP-1, BPP-2 and BPP-3) were obtained for further physicochemical properties, antioxidant activity and antibacterial activity analysis. These fractions were mainly composed of glucose, mannose and arabinose residue, meanwhile, BPP-3 had a significantly higher rhamnose and uronic acid content than BPP-1 and BPP-2. And BPP-3 showed the best hydroxyl radial scavenging activity, ferric reducing activity power (FRAP), antihemolytic activity and antibacterial activity. PMID- 27370747 TI - Antitumor and immunomodulation activities of polysaccharide from Phellinus baumii. AB - A homogeneous polysaccharide (PPB) was purified from fruiting bodies of Phellinus baumii. And in vitro antitumor and immunomodulation activities were investigated on HeLa, SGC-7901 and RAW264.7 cell lines. PPB inhibited the proliferation of HeLa and SGC-7901 cells significantly, and flow cytometric studies revealed that PPB could mediate the cell cycle in the G0/G1 and S phases. Furthermore, PPB could promote the growth and phagocytosis of RAW264.7 cells, activate the secretion of cytokines such as TNF-alpha and IL-6, which indicated that PPB had low toxicity. The results make PPB as a candidate adjuvant in cancer therapy. PMID- 27370748 TI - Cytotoxic effect of fucoidan extracted from Sargassum cinereum on colon cancer cell line HCT-15. AB - The present study was aimed to investigate the antioxidant and cytotoxicity activity against HCT-15 of fucoidan from Sargassum cinereum. Purification of fucoidan was done by DEAE cellulose and dialysis. Physicochemical characterization of fucoidan was analysed by calorimetric assay, FT-IR, HPLC and NMR. The extracted fucoidan contains 65.753% of fucose and 3.7+/-1.54% of sulphate respectively. HPLC results showed that the fucoidan contains the monosaccharide composition such as fucose, galactose, mannose and xylose. Antioxidant effect of fucoidan in Sargassum Cinereum was determined by DPPH. The maximum DPPH activity was found at the concentration of 100MUg, where as the crude extract showed the scavenging activity was 63.58+/-0.56%. Cytotoxicity effect was done by MTT assay. Fucoidan extract caused about 50% of cell death after 24h of incubation with 75+/-0.9037MUg/ml against HCT-15. PMID- 27370749 TI - Interaction of barley beta-d-glucan with wheat starch: Effect on the pasting and rheological properties. AB - In this study, the effects of barley beta-d-glucan (BBG) on the pasting and rheological properties of wheat starch (WS) were studied. Rapid visco-analyzer (RVA) results showed that addition of BBG induced a significantly increase of pasting viscosities (p<0.05). Steady shear rheological measurements showed that BBG increased the consistency index (K, Pasn) and decreased the flow behavior index (n). Higher modulus (G', G") and tan delta values were observed in dynamic viscoelasticity measurements, suggesting that the pastes were less solid-like in the presence of BBG. The median diameter of the pasted starch particles exhibited much larger than the control. The swelling power, the solubility and the amount of leached amylose increased with the increase of the BBG concentration. All the results demonstrated that BBG promoted the pasting process of WS granules, supporting that the interaction between WS and BBG could occur in the systems, which could also be confirmed by the scanning electron microscope observation. PMID- 27370751 TI - [Not Available]. PMID- 27370752 TI - [Not Available]. PMID- 27370753 TI - [Not Available]. PMID- 27370754 TI - [Not Available]. PMID- 27370750 TI - Impact and Effectiveness of Dual Aspiration Technique in Stent-Assisted Mechanical Thrombectomy: Recent Improvements in Acute Stroke Management. AB - BACKGROUND AND PURPOSE: To evaluate feasibility and impact of dual aspiration technique (DAT) within stent-assisted mechanical thrombectomy on procedural parameters and clinical outcome. MATERIALS AND METHODS: Within 16 months, 76 consecutive patients (mean age 70.7 year; range 33-89) underwent stent-assisted mechanical thrombectomy. Of 52 enrolled patients (68.4 %) with occlusion of the anterior circulation, 22 patients (42.3 %) underwent DAT; 30 patients (57.7 %) were treated in conventional monoaspiration technique (MAT). Epidemiological data, clinical and imaging characteristics (mRS, NIHSS, ASPECTS) as well as procedural details were analyzed (TICI, number of retrieval, procedure time). Clinical outcome was determined with mRS at discharge and after 90 days. RESULTS: In the context of DAT additional carotid artery stenting was required in 45.5 % (10/22) in underlying tandem lesion (vs. 0/30 MAT). No differences were found in NIHSS at admission (MAT: 20.5, range 15-29; DAT: 18.6; range 11-25), mRS at admission (MAT: 4.6 vs. DAT: 4.57) or ASPECT score (MAT: 8.3, +/-1.5; DAT: 8.4, +/-1.5; P > 0.05). TICI >= 2b/3 was conducted in 90 % (MAT) and 100 % (DAT), respectively. The procedure time was longer in the MAT group (65 min, +/-25.9, range 18-126) compared to the DAT group (49.7 min, +/-15, range 32-101; P = 0.016). The clinical outcome increased from admission to discharge and in follow up after 90 days (mRS >= 2: MAT: 53.3 %, DAT: 54.5 %; P > 0.05). CONCLUSIONS: The dual aspiration technique with an additional intermediate guide catheter placed closed to the stent retriever leads to decreased procedure time in the anterior circulation. Even in cases with higher thrombus load and treated in DAT, clinical outcome improved. PMID- 27370755 TI - [Not Available]. PMID- 27370756 TI - [Not Available]. PMID- 27370757 TI - [Not Available]. PMID- 27370758 TI - [Not Available]. PMID- 27370760 TI - [Not Available]. PMID- 27370759 TI - [Not Available]. PMID- 27370761 TI - [Not Available]. PMID- 27370762 TI - [Not Available]. PMID- 27370764 TI - [Not Available]. PMID- 27370763 TI - [Not Available]. PMID- 27370765 TI - [Not Available]. PMID- 27370766 TI - [Not Available]. PMID- 27370767 TI - [Not Available]. PMID- 27370768 TI - [Not Available]. PMID- 27370769 TI - [Not Available]. PMID- 27370770 TI - [Not Available]. PMID- 27370771 TI - [Not Available]. PMID- 27370772 TI - [Not Available]. PMID- 27370774 TI - [Not Available]. PMID- 27370773 TI - [Not Available]. PMID- 27370775 TI - [Not Available]. PMID- 27370776 TI - Diabetes mellitus and carotid artery plaques exhibiting high-intensity signals on MR angiography are related to increased platelet reactivity after carotid artery stenting. AB - BACKGROUND: Increased platelet reactivity after carotid artery stenting (CAS) may cause thromboembolic complications. OBJECTIVE: This study aimed to investigate the incidence of increased platelet reactivity after CAS and to determine the factors related to it. METHODS: Patients who underwent CAS were recruited prospectively. They received pre-procedural antiplatelet therapy comprising some combination of aspirin (100 mg/day), clopidogrel (75 mg/day), and/or cilostazol (200 mg/day) for a minimum of 7 days. ADP- and collagen-induced platelet aggregation were measured before and 4 days after CAS. Changes in platelet reactivity were reported as changes in the categorized platelet reactivity grade based on the effective dose 50%. Clinical characteristics of patients with and without increased platelet reactivity were compared. RESULTS: Among 38 consecutive patients who underwent CAS, 18 (47%) exhibited increased platelet reactivity. Diabetes mellitus (OR 15.0; 95% CI 2.1 to 106.5; p=0.007) and carotid artery plaques exhibiting high-intensity signals (HIS) on time-of-flight MR angiography (TOF-MRA) (OR 25.2; 95% CI 2.0 to 316.2; p=0.013) were independently associated with increased platelet reactivity in a multivariate analysis. CONCLUSIONS: Increased platelet reactivity occurred in nearly half of the studied patients subjected to CAS and was independently associated with diabetes mellitus and carotid artery plaques exhibiting HIS on TOF-MRA. PMID- 27370778 TI - Author Reply. PMID- 27370779 TI - Editorial Comment. PMID- 27370777 TI - Genetic basis for hyper production of hyaluronic acid in natural and engineered microorganisms. AB - Hyaluronic acid, or HA, is a rigid and linear biopolymer belonging to the class of the glycosaminoglycans, and composed of repeating units of the monosaccharides glucuronic acid and N-acetylglucosamine. HA has multiple important functions in the human body, due to its properties such as bio-compatibility, lubricity and hydrophilicity, it is widely applied in the biomedical, food, health and cosmetic fields. The growing interest in this molecule has motivated the discovery of new ways of obtaining it. Traditionally, HA has been extracted from rooster comb-like animal tissues. However, due to legislation laws HA is now being produced by bacterial fermentation using Streptococcus zooepidemicus, a natural producer of HA, despite it being a pathogenic microorganism. With the expansion of new genetic engineering technologies, the use of organisms that are non-natural producers of HA has also made it possible to obtain such a polymer. Most of the published reviews have focused on HA formulation and its effects on different body tissues, whereas very few of them describe the microbial basis of HA production. Therefore, for the first time this review has compiled the molecular and genetic bases for natural HA production in microorganisms together with the main strategies employed for heterologous production of HA. PMID- 27370780 TI - Sarcoptes scabiei infestation does not alter the stability of ectoparasite communities. AB - BACKGROUND: The host represents a heterogeneous ecosystem where multiple parasite species co-occur and interact with each other for space and resources. Although these interactions may rule the features of an infracommunity and may shape the infracommunity response to external perturbations, the resilience of ectoparasite communities to new infestations remains poorly explored. METHODS: We analysed the composition of the ectoparasite communities found on 214 individual Iberian ibexes (Capra pyrenaica) inhabiting the Sierra Nevada Natural Space, southern Spain. Using classification and regression trees, we explored how the presence of Sarcoptes scabiei (a highly contagious mite), the off-host environment and the host sex govern the prevalence and abundance of lice and ticks. Null model analysis was applied to assess the impact of S. scabiei on the structure of the ectoparasite communities. RESULTS: Our results suggest that S. scabiei infestation acts in tandem with off-host environment and host sex to define the prevalence and abundance of lice and ticks. We also provided evidence for differences in species co-occurrence only at the early stages of S. scabiei infestation. Regarding species diversity, we recorded that ectoparasite communities in scabietic ibexes reached a high richness faster than those in healthy individuals. CONCLUSIONS: Even though we show that ectoparasite burden is correlated with S. scabiei infestation, off-host environment and host sex, the species response to S. scabiei infestation and climate seem to be highly variable and influenced by ectoparasite life-history traits. Ectoparasite communities also appear resilient to perturbations which is in agreement with what was previously reported for endoparasites. Future refinement of sample collection and the incorporation of ecological and epidemiological-related variables may allow us to establish causal effects and deepen the knowledge about the mechanisms and consequences of ectoparasite interactions. PMID- 27370782 TI - Optimal graft stiffness and pre-strain restore normal joint motion and cartilage responses in ACL reconstructed knee. AB - Anterior cruciate ligament (ACL) rupture leads to abnormal loading of the knee joint and increases the risk of osteoarthritis. It is unclear how different ACL reconstruction techniques affect knee joint motion and mechanics. As the in vivo measurement of knee joint loading is not possible, we used finite element analysis to assess the outcome of ACL reconstruction techniques. Effects of different ACL reconstruction techniques on knee joint mechanics were studied using six models during gait; with 1) healthy ACL, 2) ACL rupture, 3) single bundle ACL reconstruction, 4) double bundle ACL reconstruction, 5) weakened (softer) single bundle reconstruction and 6) single bundle reconstruction with less pre-strain. Early in the gait, the ACL rupture caused substantially increased tibial translation in the anterior direction as well as a smaller but increased lateral translation and internal tibial rotation. ACL rupture substantially reduced average stresses and strains, while local peak stresses and strains could be either increased or decreased. Single bundle and double bundle reconstructions restored joint motion close to normal levels. However, cartilage strains and stresses were elevated during the entire gait cycle. Models with modulated graft stiffness and pre-strain restored the joint motion and cartilage stresses and strains close to the normal, healthy levels. Results suggest that rather than the choice of reconstruction technique, stiffness and pre-strain of the ACL reconstruction affect the motion and mechanics of the operated knee. We suggest that an optimal choice of graft properties might help restore normal knee joint function and cartilage responses, thus, minimizing the risk of osteoarthritis. PMID- 27370781 TI - Classical risk factors, but not HPV status, predict survival after chemoradiotherapy in advanced head and neck cancer patients. AB - PURPOSE: Despite the advent of concomitant chemoradiotherapy (CCRT), the prognosis of advanced head and neck squamous cell carcinoma (HNSCC) patients remains particularly poor. Classically, HNSCC, especially oropharyngeal carcinomas, associated with human papillomavirus (HPV) exhibits better treatment outcomes than HNSCCs in non-infected patients, eliciting a call for the de escalation of current therapies. To improve the management of HNSCC patients, we aimed to determine the impact of active HPV infection on patient response, recurrence and survival after CCRT in a population of heavy tobacco and alcohol consumers. METHODS: Paraffin-embedded samples from 218 advanced HNSCC patients, mostly smokers and/or drinkers treated by CCRT, were tested for the presence of HPV DNA by surrogate type-specific E6/E7 qPCR and p16 immunohistochemistry. Associations between the response to CCRT and patient outcomes according to HPV status and clinical data were evaluated by Kaplan-Meier analysis and both univariate and multivariate Cox regression. RESULTS: Type-specific E6/E7 PCR demonstrated HPV positivity in 20 % of HNSCC. Regarding HPV status, we did not find any significant relation with response to therapy in terms of progression free survival or overall survival. However, we observed a significantly worse prognosis for consumers of alcohol and tobacco compared to nondrinkers (p = 0.003) and non-smokers (p = 0.03). Survival analyses also revealed that the outcome is compromised in stage IV patients (p = 0.007) and, in particular, for oral cavity, hypopharynx and oropharynx carcinoma patients (p = 0.001). CONCLUSION: The risk of death from HNSCC significantly increases when patients are exposed to tobacco and alcohol during their therapy, regardless of HPV status. PMID- 27370783 TI - Using wave intensity analysis to determine local reflection coefficient in flexible tubes. AB - It has been shown that reflected waves affect the shape and magnitude of the arterial pressure waveform, and that reflected waves have physiological and clinical prognostic values. In general the reflection coefficient is defined as the ratio of the energy of the reflected to the incident wave. Since pressure has the units of energy per unit volume, arterial reflection coefficient are traditionally defined as the ratio of reflected to the incident pressure. We demonstrate that this approach maybe prone to inaccuracies when applied locally. One of the main objectives of this work is to examine the possibility of using wave intensity, which has units of energy flux per unit area, to determine the reflection coefficient. We used an in vitro experimental setting with a single inlet tube joined to a second tube with different properties to form a single reflection site. The second tube was long enough to ensure that reflections from its outlet did not obscure the interactions of the initial wave. We generated an approximately half sinusoidal wave at the inlet of the tube and took measurements of pressure and flow along the tube. We calculated the reflection coefficient using wave intensity (RdI and RdI0.5) and wave energy (RI and RI0.5) as well as the measured pressure (RdP) and compared these results with the reflection coefficient calculated theoretically based on the mechanical properties of the tubes. The experimental results show that the reflection coefficients determined by all the techniques we studied increased or decreased with distance from the reflection site, depending on the type of reflection. In our experiments, RdP, RdI0.5 and RI0.5 are the most reliable parameters to measure the mean reflection coefficient, whilst RdI and RI provide the best measure of the local reflection coefficient, closest to the reflection site. Additional work with bifurcations, tapered tubes and in vivo experiments are needed to further understand, validate the method and assess its potential clinical use. PMID- 27370784 TI - A high current pulsed power generator CQ-3-MMAF with co-axial cable transmitting energy for material dynamics experiments. AB - A high current pulsed power generator CQ-3-MMAF (Multi-Modules Assembly Facility, MMAF) was developed for material dynamics experiments under ramp wave and shock loadings at the Institute of Fluid Physics (IFP), which can deliver 3 MA peak current to a strip-line load. The rise time of the current is 470 ns (10%-90%). Different from the previous CQ-4 at IFP, the CQ-3-MMAF energy is transmitted by hundreds of co-axial high voltage cables with a low impedance of 18.6 mOmega and low loss, and then hundreds of cables are reduced and converted to tens of cables into a vacuum chamber by a cable connector, and connected with a pair of parallel metallic plates insulated by Kapton films. It is composed of 32 capacitor and switch modules in parallel. The electrical parameters in short circuit are with a capacitance of 19.2 MUF, an inductance of 11.7 nH, a resistance of 4.3 mOmega, and working charging voltage of 60 kV-90 kV. It can be run safely and stable when charged from 60 kV to 90 kV. The vacuum of loading chamber can be up to 10(-2) Pa, and the current waveforms can be shaped by discharging in time sequences of four groups of capacitor and switch modules. CQ-3-MMAF is an adaptive machine with lower maintenance because of its modularization design. The COMSOL Multi physics(r) code is used to optimize the structure of some key components and calculate their structural inductance for designs, such as gas switches and cable connectors. Some ramp wave loading experiments were conducted to check and examine the performances of CQ-3-MMAF. Two copper flyer plates were accelerated to about 3.5 km/s in one shot when the working voltage was charged to 70 kV. The velocity histories agree very well. The dynamic experiments of some polymer bonded explosives and phase transition of tin under ramp wave loadings were also conducted. The experimental data show that CQ-3-MMAF can be used to do material dynamics experiments in high rate and low cost shots. Based on this design concept, the peak current of new generators can be increased to 5-6 MA and about 100 GPa ramp stress can be produced on the metallic samples for high pressure physics, and a conceptual design of CQ-5-MMAF was given. PMID- 27370785 TI - Predicting 3D lip movement using facial sEMG: a first step towards estimating functional and aesthetic outcome of oral cancer surgery. AB - In oral cancer, loss of function due to surgery can be unacceptable, designating the tumour as functionally inoperable. Other curative treatments can then be considered. Currently, predictions of these functional consequences are subjective and unreliable. We want to create patient-specific models to improve and objectify these predictions. A first step was taken by controlling a 3D lip model with volunteer-specific sEMG activities. We focus on the lips first, because they are essential for speech, oral food transport, and facial mimicry. Besides, they are more accessible to measurements than intraoral organs. 3D lip movement and corresponding sEMG activities are measured in five healthy volunteers, who performed 19 instructions repeatedly, to create a quantitative lip model by establishing the relationship between sEMG activities of eight facial muscles bilaterally on the input side and the corresponding 3D lip displacements on the output side. The relationship between 3D lip movement and sEMG activities was accommodated in a state-space model. A good relationship between sEMG activities and 3D lip movement was established with an average root mean square error of 2.43 mm for the first-order system and 2.46 mm for the second-order system. This information can be incorporated into biomechanical models to further personalise functional outcome assessment after treatment. PMID- 27370786 TI - Post-stimulation block of frog sciatic nerve by high-frequency (kHz) biphasic stimulation. AB - This study determined if high-frequency biphasic stimulation can induce nerve conduction block that persists after the stimulation is terminated, i.e., post stimulation block. The frog sciatic nerve-muscle preparation was used in the study. Muscle contraction force induced by low-frequency (0.5 Hz) nerve stimulation was recorded to indicate the occurrence and recovery of nerve block induced by the high-frequency (5 or 10 kHz) biphasic stimulation. Nerve block was observed during high-frequency stimulation and after termination of the stimulation. The recovery from post-stimulation block occurred in two distinct phases. During the first phase, the complete block induced during high-frequency stimulation was maintained. The average maximal duration for the first phase was 107 +/- 50 s. During the second phase, the block gradually or abruptly reversed. The duration of both first and second phases was dependent on stimulation intensity and duration but not frequency. Stimulation of higher intensity (1.4-2 times block threshold) and longer duration (5 min) produced the longest period (249 +/- 58 s) for a complete recovery. Post-stimulation block can be induced by high-frequency biphasic stimulation, which is important for future investigations of the blocking mechanisms and for optimizing the stimulation parameters or protocols in clinical applications. PMID- 27370787 TI - Magneto-acoustic imaging by continuous-wave excitation. AB - The electrical characteristics of tissue yield valuable information for early diagnosis of pathological changes. Magneto-acoustic imaging is a functional approach for imaging of electrical conductivity. This study proposes a continuous wave magneto-acoustic imaging method. A kHz-range continuous signal with an amplitude range of several volts is used to excite the magneto-acoustic signal and improve the signal-to-noise ratio. The magneto-acoustic signal amplitude and phase are measured to locate the acoustic source via lock-in technology. An optimisation algorithm incorporating nonlinear equations is used to reconstruct the magneto-acoustic source distribution based on the measured amplitude and phase at various frequencies. Validation simulations and experiments were performed in pork samples. The experimental and simulation results agreed well. While the excitation current was reduced to 10 mA, the acoustic signal magnitude increased up to 10-7 Pa. Experimental reconstruction of the pork tissue showed that the image resolution reached mm levels when the excitation signal was in the kHz range. The signal-to-noise ratio of the detected magneto-acoustic signal was improved by more than 25 dB at 5 kHz when compared to classical 1 MHz pulse excitation. The results reported here will aid further research into magneto acoustic generation mechanisms and internal tissue conductivity imaging. PMID- 27370788 TI - Device-based Therapy for Hypertension. AB - Hypertension continues to be a major contributor to global morbidity and mortality, fuelled by an abundance of patients with uncontrolled blood pressure despite the multitude of pharmacological options available. This may occur as a consequence of true resistant hypertension, through an inability to tolerate current pharmacological therapies, or non-adherence to antihypertensive medication. In recent years, there has been a rapid expansion of device-based therapies proposed as novel non-pharmacological approaches to treating resistant hypertension. In this review, we discuss seven novel devices-renal nerve denervation, baroreflex activation therapy, carotid body ablation, central iliac arteriovenous anastomosis, deep brain stimulation, median nerve stimulation, and vagal nerve stimulation. We highlight how the devices differ, the varying degrees of evidence available to date and upcoming trials. This review also considers the possible factors that may enable appropriate device selection for different hypertension phenotypes. PMID- 27370789 TI - Systematic Review and Meta-Analyses of Perinatal Death and Maternal Exposure to Tobacco Smoke During Pregnancy. AB - We conducted a systematic review and 3-part meta-analysis to characterize the relationship between smoking and perinatal death, defined as the combination of stillbirth and neonatal death. The PubMed database was searched (1956-August 31, 2011) with keywords, and manual reference searches of included articles and Surgeon Generals' reports were conducted. The full texts of 1,713 articles were reviewed, and 142 articles that examined the associations between active or passive smoking and perinatal death were included in the meta-analyses. Data were abstracted by 2 reviewers. Any active maternal smoking was associated with increased risks of stillbirth (summary relative risk (sRR) = 1.46, 95% confidence interval (CI): 1.38, 1.54 (n = 57 studies)), neonatal death (sRR = 1.22, 95% CI: 1.14, 1.30 (n = 28)), and perinatal death (sRR = 1.33, 95% CI: 1.25, 1.41 (n = 46)). The risks of stillbirth, neonatal death, and perinatal death increased with the amount smoked by the mother. Biases in study publication, design, and analysis were present but did not significantly affect the results. These findings strengthen the evidence that women should not smoke while pregnant, and all women of reproductive age should be warned that smoking increases the risks of stillbirth, neonatal death, and perinatal death. PMID- 27370790 TI - Fetal Growth and the Risk of Spontaneous Preterm Birth in a Prospective Cohort Study of Nulliparous Women. AB - Previous studies have suggested an association between fetal growth restriction and the risk of spontaneous preterm birth (sPTB). However, addressing this association is methodologically challenging. We conducted a prospective cohort study of nulliparous women with a singleton pregnancy in Cambridge, United Kingdom (2008-2012). Ultrasonic fetal biometry was performed at 20 weeks of gestation as per routine clinical care. Participants also had blinded research ultrasonography performed at approximately 28 weeks. Biometric measurements were expressed as gestational-age-adjusted z scores. Fetal growth velocity was quantified by change in z score between 20 weeks and 28 weeks. Risk of sPTB, defined as delivery at >=28 weeks and <37 weeks associated with labor in the absence of induction, was analyzed using cause-specific Cox regression. Of 3,892 women, 98 (2.5%) had sPTB. When compared with the other decile groups, the lowest decile of growth velocity of the fetal femur between 20 and 28 weeks was associated with increased risk of sPTB (hazard ratio = 2.37, 95% confidence interval: 1.43, 3.93; P < 0.001). Adjustment for maternal characteristics had no material effect (hazard ratio = 2.50, 95% confidence interval: 1.50, 4.14; P < 0.001). There were no significant associations between other fetal measurements and risk of sPTB. To conclude, slow growth velocity of the fetal femur is associated with an increased risk of sPTB. PMID- 27370792 TI - Occupational Noise Frequencies and the Incidence of Hypertension in a Retrospective Cohort Study. AB - Occupational noise exposure is associated with cardiovascular disease, but little is known about the contributions of noise frequency components. This retrospective study investigated the relationship between exposure to different noise frequencies and the incidence of hypertension. A cohort of 1,002 volunteers from 4 machinery and equipment manufacturing companies in Taichung, Taiwan, was followed from 1973 to 2012. Personal noise measurements and environmental octave band analyses were performed to divide subjects into different exposure groups. Cox regression models were used to estimate the relative risk of hypertension. Participants exposed to >=80 A-weighted decibels (dBA) over 8 years had a higher relative risk of hypertension (relative risk = 1.38, 95% confidence interval: 1.02, 1.85) compared with those exposed to <75 dBA. Significant exposure-response patterns were observed between incident hypertension and stratum of noise exposure at frequencies of 250 Hz, 1 kHz, 2 kHz, 4 kHz, and 8 kHz. The strongest effect was found at 4 kHz; a 20-dBA increase in noise exposure at 4 kHz was associated with a 34% higher risk of hypertension (relative risk = 1.34, 95% confidence interval: 1.01, 1.77). Occupational noise exposure may be associated with an increased risk of hypertension, and the 4 kHz component of occupational noise exposure may have the strongest relationship with hypertension. PMID- 27370791 TI - Anthropometry and the Risk of Lung Cancer in EPIC. AB - The associations of body mass index (BMI) and other anthropometric measurements with lung cancer were examined in 348,108 participants in the European Investigation Into Cancer and Nutrition (EPIC) between 1992 and 2010. The study population included 2,400 case patients with incident lung cancer, and the average length of follow-up was 11 years. Hazard ratios were calculated using Cox proportional hazard models in which we modeled smoking variables with cubic splines. Overall, there was a significant inverse association between BMI (weight (kg)/height (m)(2)) and the risk of lung cancer after adjustment for smoking and other confounders (for BMI of 30.0-34.9 versus 18.5-25.0, hazard ratio = 0.72, 95% confidence interval: 0.62, 0.84). The strength of the association declined with increasing follow-up time. Conversely, after adjustment for BMI, waist circumference and waist-to-height ratio were significantly positively associated with lung cancer risk (for the highest category of waist circumference vs. the lowest, hazard ratio = 1.25, 95% confidence interval: 1.05, 1.50). Given the decline of the inverse association between BMI and lung cancer over time, the association is likely at least partly due to weight loss resulting from preclinical lung cancer that was present at baseline. Residual confounding by smoking could also have influenced our findings. PMID- 27370793 TI - Evaluation of antimicrobial activity and probiotic properties of wild-strain Pichia kudriavzevii isolated from frozen idli batter. AB - The present research was undertaken to study the probiotic characteristics of Pichia kudriavzevii isolated from frozen idli batter. Polymerase chain reaction amplification with 18S rRNA primers confirmed Pichia kudriavzevii, a xylose utilizing probiotic strain. It was resistant to physiological concentrations of bile salts, pepsin and pancreatic enzyme. It also showed efficient auto aggregation as well as co-aggregation ability with four commercial probiotic yeasts and exhibited good hydrophobicity in xylene and toluene. The strain inhibited the growth of 13 enteropathogens and showed a commensal relationship with four commercial probiotic yeast and bacteria. Moreover, it was resistant to 30 antibiotics with different modes of action. The yeast exhibited thermotolerance up to 95 degrees C for 2 h. The cell-free supernatants were also found to be heat stable, indicating the presence of thermostable secondary metabolites. Hence it could be exploited as starter culture, co-culture or probiotic in the preparation of fermented products or incorporated in heatable foods as well. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27370794 TI - Heteroreceptor Complexes Formed by Dopamine D1, Histamine H3, and N-Methyl-D Aspartate Glutamate Receptors as Targets to Prevent Neuronal Death in Alzheimer's Disease. AB - Alzheimer's disease (AD) is a neurodegenerative disorder causing progressive memory loss and cognitive dysfunction. Anti-AD strategies targeting cell receptors consider them as isolated units. However, many cell surface receptors cooperate and physically contact each other forming complexes having different biochemical properties than individual receptors. We here report the discovery of dopamine D1, histamine H3, and N-methyl-D-aspartate (NMDA) glutamate receptor heteromers in heterologous systems and in rodent brain cortex. Heteromers were detected by co-immunoprecipitation and in situ proximity ligation assays (PLA) in the rat cortex where H3 receptor agonists, via negative cross-talk, and H3 receptor antagonists, via cross-antagonism, decreased D1 receptor agonist signaling determined by ERK1/2 or Akt phosphorylation, and counteracted D1 receptor-mediated excitotoxic cell death. Both D1 and H3 receptor antagonists also counteracted NMDA toxicity suggesting a complex interaction between NMDA receptors and D1-H3 receptor heteromer function. Likely due to heteromerization, H3 receptors act as allosteric regulator for D1 and NMDA receptors. By bioluminescence resonance energy transfer (BRET), we demonstrated that D1 or H3 receptors form heteromers with NR1A/NR2B NMDA receptor subunits. D1-H3-NMDA receptor complexes were confirmed by BRET combined with fluorescence complementation. The endogenous expression of complexes in mouse cortex was determined by PLA and similar expression was observed in wild-type and APP/PS1 mice. Consistent with allosteric receptor-receptor interactions within the complex, H3 receptor antagonists reduced NMDA or D1 receptor-mediated excitotoxic cell death in cortical organotypic cultures. Moreover, H3 receptor antagonists reverted the toxicity induced by beta1-42-amyloid peptide. Thus, histamine H3 receptors in D1-H3-NMDA heteroreceptor complexes arise as promising targets to prevent neurodegeneration. PMID- 27370795 TI - The Expression of Toll-like Receptors in Normal Human and Murine Gastrointestinal Organs and the Effect of Microbiome and Cancer. AB - Toll-like receptors (TLRs) are innate immune receptors expressed in all parts of the alimentary tract. However, analyses comparing expression in different segments and data on germ-free animals are lacking. Alimentary tract cancers show increased TLR expression. According to the field effect concept, carcinogenetic factors induce subtle cancer predisposing alterations in the whole organ. We studied TLR1 to TLR9 expression in all segments of the alimentary tract from cancer patients' tumor-adjacent normal mucosa, healthy organ donors, and conventional and germ-free mice by using immunohistochemistry and quantitative PCR. All TLRs were expressed in all segments of the alimentary tract. Expression was most intensive in the small intestine in humans and conventional mice, but germ-free mice showed less expression in the small intestine. TLR expression levels were similar in cancer patients and organ donors. We provide systematic baseline data on the TLR expression in the alimentary tract. Normal epithelium adjacent to tumor seems to have similar TLR expression compared with healthy tissues suggesting absence of any field effect in TLR expression. Accordingly, specimens from cancer patients' normal tumor-adjacent tissue can be used as control tissues in immunohistochemical TLR studies in gastrointestinal cancer. PMID- 27370796 TI - Toxoplasma gondii Infection Promotes Epithelial Barrier Dysfunction of Caco-2 Cells. AB - After oral infection, Toxoplasma gondii invades intestinal cells, induces breakdown of intestinal physiology and barrier functions, and causes intestinal pathology in some animal species. Although parasites' invasion into host cells is a known phenomenon, the effects of T. gondii infection in the intestinal barrier are still not well established. To evaluate morphological and physiological modifications on the colorectal adenocarcinoma-derived Caco-2 cell line during T. gondii infection, microvilli, tight junction integrity, and transepithelial electrical resistance (TEER) were investigated under infection. It was observed that the dextran uptake (endocytosis) and distribution were smaller in infected than in noninfected Caco-2 cells. The infection leads to the partial loss of microvilli at the cell surface. Claudin-1, zonula occludens-1 (ZO-1), and occludin expressions were colocalized by immunofluorescence and presented discontinuous net patterns in infected cells. Immunoblotting analysis at 24 hr postinfection revealed decreasing expression of occludin and ZO-1 proteins, whereas claudin-1 presented similar expression level compared with noninfected cells. T. gondii decreased TEER in Caco-2 cells 24 hr after infection. Our results suggest that T. gondii infection may lead to the loss of integrity of intestinal mucosa, resulting in impaired barrier function. PMID- 27370797 TI - Tissue Inhibitor of Metalloproteinase-1 Is Confined to Tumor-Associated Myofibroblasts and Is Increased With Progression in Gastric Adenocarcinoma. AB - The tissue inhibitor of metalloproteinase-1 (TIMP-1) inhibits the extracellular matrix-degrading activity of several matrix metalloproteinases, thereby regulating cancer cell invasion and metastasis. Studies describing the expression pattern and cellular localization of TIMP-1 in gastric cancer are, however, highly discordant. We addressed these inconsistencies by performing immunohistochemistry and in situ hybridization analyses in a set of 49 gastric cancer lesions to reexamine the TIMP-1 localization. In addition, we correlated these findings to clinicopathological parameters. We show that strong expression of TIMP-1 protein and mRNA was observed in a subpopulation of stromal fibroblast like cells at the periphery of the cancer lesions. In a few cases, a small fraction of cancer cells showed weak expression of TIMP-1 protein and mRNA. The stromal TIMP-1-expressing cells were mainly tumor-associated myofibroblasts. In the normal-appearing mucosa, scattered TIMP-1 protein was only found in chromogranin A positive cells. TIMP-1-positive myofibroblasts at the invasive front of the tumors were more frequently seen in intestinal than in diffuse histological subtype cases (p=0.009). A significant trend to a higher number of cases showing TIMP-1 staining in myofibroblasts with increasing tumor, node, metastasis (TNM) stage was also revealed (p=0.041). In conclusion, tumor associated myofibroblasts are the main source of increased TIMP-1 expression in gastric cancer. PMID- 27370799 TI - High-resolution X-ray absorption spectroscopy as a probe of crystal-field and covalency effects in actinide compounds. AB - Applying the high-energy resolution fluorescence-detection (HERFD) mode of X-ray absorption spectroscopy (XAS), we were able to probe, for the first time to our knowledge, the crystalline electric field (CEF) splittings of the [Formula: see text] shell directly in the HERFD-XAS spectra of actinides. Using ThO2 as an example, data measured at the Th 3d edge were interpreted within the framework of the Anderson impurity model. Because the charge-transfer satellites were also resolved in the HERFD-XAS spectra, the analysis of these satellites revealed that ThO2 is not an ionic compound as previously believed. The Th [Formula: see text] occupancy in the ground state was estimated to be twice that of the Th [Formula: see text] states. We demonstrate that HERFD-XAS allows for characterization of the CEF interaction and degree of covalency in the ground state of actinide compounds as it is extensively done for 3d transition metal systems. PMID- 27370798 TI - Phosphotyrosine-mediated LAT assembly on membranes drives kinetic bifurcation in recruitment dynamics of the Ras activator SOS. AB - The assembly of cell surface receptors with downstream signaling molecules is a commonly occurring theme in multiple signaling systems. However, little is known about how these assemblies modulate reaction kinetics and the ultimate propagation of signals. Here, we reconstitute phosphotyrosine-mediated assembly of extended linker for the activation of T cells (LAT):growth factor receptor bound protein 2 (Grb2):Son of Sevenless (SOS) networks, derived from the T-cell receptor signaling system, on supported membranes. Single-molecule dwell time distributions reveal two, well-differentiated kinetic species for both Grb2 and SOS on the LAT assemblies. The majority fraction of membrane-recruited Grb2 and SOS both exhibit fast kinetics and single exponential dwell time distributions, with average dwell times of hundreds of milliseconds. The minor fraction exhibits much slower kinetics, extending the dwell times to tens of seconds. Considering this result in the context of the multistep process by which the Ras GEF (guanine nucleotide exchange factor) activity of SOS is activated indicates that kinetic stabilization from the LAT assembly may be important. This kinetic proofreading effect would additionally serve as a stochastic noise filter by reducing the relative probability of spontaneous SOS activation in the absence of receptor triggering. The generality of receptor-mediated assembly suggests that such effects may play a role in multiple receptor proximal signaling processes. PMID- 27370800 TI - Gene targeting of the transcription factor Mohawk in rats causes heterotopic ossification of Achilles tendon via failed tenogenesis. AB - Cell-based or pharmacological approaches for promoting tendon repair are currently not available because the molecular mechanisms of tendon development and healing are not well understood. Although analysis of knockout mice provides many critical insights, small animals such as mice have some limitations. In particular, precise physiological examination for mechanical load and the ability to obtain a sufficient number of primary tendon cells for molecular biology studies are challenging using mice. Here, we generated Mohawk (Mkx)(-/-) rats by using CRISPR/Cas9, which showed not only systemic hypoplasia of tendons similar to Mkx(-/-) mice, but also earlier heterotopic ossification of the Achilles tendon compared with Mkx(-/-) mice. Analysis of tendon-derived cells (TDCs) revealed that Mkx deficiency accelerated chondrogenic and osteogenic differentiation, whereas Mkx overexpression suppressed chondrogenic, osteogenic, and adipogenic differentiation. Furthermore, mechanical stretch stimulation of Mkx(-/-) TDCs led to chondrogenic differentiation, whereas the same stimulation in Mkx(+/+) TDCs led to formation of tenocytes. ChIP-seq of Mkx overexpressing TDCs revealed significant peaks in tenogenic-related genes, such as collagen type (Col)1a1 and Col3a1, and chondrogenic differentiation-related genes, such as SRY box (Sox)5, Sox6, and Sox9 Our results demonstrate that Mkx has a dual role, including accelerating tendon differentiation and preventing chondrogenic/osteogenic differentiation. This molecular network of Mkx provides a basis for tendon physiology and tissue engineering. PMID- 27370801 TI - Sympatric speciation of spiny mice, Acomys, unfolded transcriptomically at Evolution Canyon, Israel. AB - Spiny mice, Acomys cahirinus, colonized Israel 30,000 y ago from dry tropical Africa and inhabited rocky habitats across Israel. Earlier, we had shown by mtDNA that A. cahirinus incipiently sympatrically speciates at Evolution Canyon I (EC I) in Mount Carmel, Israel because of microclimatic interslope divergence. The EC I microsite consists of a dry and hot savannoid "African" slope (AS) and an abutting humid and cool-forested "European" slope (ES). Here, we substantiate incipient SS in A. cahirinus at EC I based on the entire transcriptome, showing that multiple slope-specific adaptive complexes across the transcriptome result in two divergent clusters. Tajima's D distribution of the abutting Acomys interslope populations shows that the ES population is under stronger positive selection, whereas the AS population is under balancing selection, harboring higher genetic polymorphisms. Considerable sites of the two populations were differentiated with a coefficient of FST = 0.25-0.75. Remarkably, 24 and 37 putatively adaptively selected genes were detected in the AS and ES populations, respectively. The AS genes involved DNA repair, growth arrest, neural cell differentiation, and heat-shock proteins adapting to the local AS stresses of high solar radiation, drought, and high temperature. In contrast, the ES genes involved high ATP associated with energetics stress. The sharp ecological interslope divergence led to strong slope-specific selection overruling the interslope gene flow. Earlier tests suggested slope-specific mate choice. Habitat interslope-adaptive selection across the transcriptome and mate choice substantiate sympatric speciation (SS), suggesting its prevalence at EC I and commonality in nature. PMID- 27370802 TI - Parents of children having heart surgery at Bristol hospital "were let down". PMID- 27370803 TI - [Not Available]. PMID- 27370804 TI - [Not Available]. PMID- 27370806 TI - [Not Available]. PMID- 27370805 TI - [Not Available]. PMID- 27370807 TI - [Not Available]. PMID- 27370809 TI - [Not Available]. PMID- 27370808 TI - [Not Available]. PMID- 27370810 TI - [Not Available]. PMID- 27370811 TI - [Not Available]. PMID- 27370812 TI - [Not Available]. PMID- 27370813 TI - [Not Available]. PMID- 27370814 TI - [Not Available]. PMID- 27370815 TI - [Not Available]. PMID- 27370816 TI - No Reduction in Hemoglobin Level in Severe Plasmodium falciparum Malaria Treated with Artesunate in Central Sudan. AB - BACKGROUND: There are few publications on anemia following artesunate treatment. OBJECTIVE: To investigate the hemoglobin in patients with severe Plasmodium falciparum malaria treated with artesunate or quinine. METHODS: Patients with P. falciparum (in Singa, Sudan) were treated by intravenous artesunate or quinine. Hemoglobin was measured initially, at day 14 and day 28. RESULTS: The mean (SD) of the age was 10.3 (10.9) years. The two groups (61 in each arm) were matched in their basic characteristics. Hypotension, convulsions, severe anemia were the main presentations. There was no significant difference in the mean (SD) hemoglobin level at the initial day, day 14 and at day 28 [11.2 (1.8), 11.3 (1.6), 11.5 (1.8), p = 0.170], respectively, in both groups. The hemoglobin did not change significantly from the baseline in any of the group separately. CONCLUSION: There was no difference in hemoglobin concentration in patients with severe malaria after treatment with either artesunate or quinine. PMID- 27370817 TI - Use of Camphor and Essential Oil Balms for Infants in Cambodia. AB - Balms and oils containing terpenic compounds, such as camphor, menthol and eucalyptus, are potentially toxic, and numerous reports of adverse events stemming from their use in infants and young children have been published. During qualitative research on newborn practices in rural Cambodia, these products were found to be commonly applied to the skin of newborns and infants and available in most households. Parents and caregivers of infants in Cambodia and other settings where use of camphor- and menthol-containing products are common should be educated on the risks of these to prevent child morbidity and potential mortality. PMID- 27370818 TI - Bladder pain induced by prolonged peripheral alpha 1A adrenoceptor stimulation involves the enhancement of transient receptor potential vanilloid 1 activity and an increase of urothelial adenosine triphosphate release. AB - AIM: Pathophysiological mechanisms of chronic visceral pain (CVP) are unknown. This study explores the association between the sympathetic system and bladder nociceptors activity by testing the effect of a prolonged adrenergic stimulation on transient receptor potential vanilloid 1 (TRPV1) activity and on urothelial adenosine triphosphate (ATP) release. METHODS: Female Wistar rats received saline, phenylephrine (PHE), PHE + silodosin, PHE + naftopidil or PHE + prazosin. TRPV1 knockout and wild-type mice received saline or PHE. Visceral pain behaviour tests were performed before and after treatment. Cystometry was performed, during saline and capsaicin infusion. Fos immunoreactivity was assessed in L6 spinal cord segment. Human urothelial ATP release induced by mechanical and thermal stimulation was evaluated. RESULTS: Subcutaneous, but not intrathecal, PHE administration induced pain, which was reversed by silodosin, a selective alpha 1A adrenoceptor antagonist, but not by naftopidil, a relatively selective antagonist for alpha 1D adrenoceptor. Silodosin also reversed PHE-induced bladder hyperactivity and L6 spinal cord Fos expression. Thus, in subsequent experiments, only silodosin was used. Wild-type, but not TRPV1 knockout, mice exhibited phenylephrine-induced pain. Capsaicin induced a greater increase in voiding contractions in PHE-treated rats than in control animals, and silodosin reversed this effect. When treated with PHE, ATP release from human urothelial cells was enhanced either by mechanical stimulation or by lowering the thermal threshold of urothelial TRPV1, which becomes abnormally responsive at body temperature. CONCLUSION: This study suggests that the activation of peripheral alpha 1A adrenoceptors induces CVP, probably through its interaction with TRPV1 and ATP release. PMID- 27370819 TI - Effects of Copper Exposure on Photosynthesis and Growth of the Seagrass Cymodocea nodosa: An Experimental Assessment. AB - Seagrasses form some of the most important coastal habitats. They may be negatively affected by trace metal contamination in certain coastal areas. In this study we experimentally assessed selected morphological and physiological traits of the seagrass Cymodocea nodosa, with increasing concentrations of copper (Cu) under controlled laboratory conditions. Short term (21 days) sub-lethal effects such as decreased maximum quantum yield, increased leaf necrosis and decreased shoot growth and shoot recruitment were clearly observed at the highest Cu exposure (5 mg L(-1)), while the effects were weaker at the intermediate concentration (2.5 mg L(-1)) and almost absent at the lowest concentration (1 mg L(-1)), indicating that this species is highly tolerant to copper exposure, at least in the short term. This fact could help to explain its distribution in relatively polluted coastal waters. PMID- 27370820 TI - Impact of Irrigation Using Water Containing CuO and ZnO Nanoparticles on Spinach oleracea Grown in Soil Media. AB - Wastewater reuse is an important adaptation option for mitigating water stress in rapidly growing urban centers. Reuse potential of nanoparticles (NPs) contaminated wastewater for irrigation of Spinacia oleracea grown in soil media were assessed in this study. Irrigation of plant were done with water containing CuO and ZnO NPs as single compound and in binary mixture (10, 100, 1000 mg/L) till 11 weeks. At 1000 mg/L, reduction in root length: 16 %, 12 % and 18 %, shoot length: 22 %, 16 % and 27 %, total weight 37 %, 27 % and 45 %, chlorophyll: 18 %, 7 % and 29 % and carotenoids: 46 %, 33 % and 54 % were found for CuO NPs, ZnO NPs and binary mixture of NPs respectively. Uptake values were found to be 5.65 +/- 0.8 Zn(2+) and 3.48 +/- 0.75 Cu(2+) mg/g for the case of ZnO and CuO NPs respectively (at 1000 mg/L). For mixture of NPs, uptake of 3.18 +/- 1.05 mg/g of Cu(2+) and 3.18 +/- 1.05 mg/g of Zn(2+) ions were found. The results shows that water containing low concentration of NPs (10 mg/L) can be used for irrigating spinach grown in soil media as no significant toxic effect on growth and uptake of metal ion were found as compared to control. The results of this study evaluated the suitability of reusing water contaminated with NPs in agriculture. Further studies are however required to understand the toxic mode of action of mixture of NPs on growth and uptake mechanisms. PMID- 27370821 TI - Levels of Mercury in Feathers of Clapper Rails (Rallus crepitans) over 45 Years in Coastal Salt Marshes of New Hanover County, North Carolina. AB - We sampled clapper rail (Rallus crepitans) feathers from museum specimens collected between 1965 and 2010 to investigate changes in mercury (Hg) availability in coastal marshes of New Hanover County, North Carolina. Stable isotope analysis (delta(13)C and delta(15)N) was conducted to control for dietary shifts that may have influenced Hg exposure. Hg concentrations ranged from 0.96 to 9.22 MUg/g (ppm), but showed no significant trend over time; diet (delta(15)N) or foraging habitat (delta(13)C) also provided little to no explanatory power to the variation in Hg concentrations among clapper rails. Our findings suggest the bioavailability of Hg to clapper rails in coastal North Carolina salt marshes has remained consistent over time, despite the global trend of increasing mercury in many other bird species, providing an excellent baseline for any future assessment of Hg availability to salt marsh birds in coastal North Carolina. PMID- 27370823 TI - [Not Available]. PMID- 27370824 TI - [Not Available]. PMID- 27370822 TI - Disrupted-in-schizophrenia 1 (DISC1) and Syntaphilin collaborate to modulate axonal mitochondrial anchoring. AB - In neuronal axons, the ratio of motile-to-stationary mitochondria is tightly regulated by neuronal activation, thereby meeting the need for local calcium buffering and maintaining the ATP supply. However, the molecular players and detailed regulatory mechanisms behind neuronal mitochondrial movement are not completely understood. Here, we found that neuronal activation-induced mitochondrial anchoring is regulated by Disrupted-in-schizophrenia 1 (DISC1), which is accomplished by functional association with Syntaphilin (SNPH). DISC1 deficiency resulted in reduced axonal mitochondrial movement, which was partially reversed by concomitant SNPH depletion. In addition, a SNPH deletion mutant lacking the sequence for interaction with DISC1 exhibited an enhanced mitochondrial anchoring effect than wild-type SNPH. Moreover, upon neuronal activation, mitochondrial movement was preserved by DISC1 overexpression, not showing immobilized response of mitochondria. Taken together, we propose that DISC1 in association with SNPH is a component of a modulatory complex that determines mitochondrial anchoring in response to neuronal activation. PMID- 27370826 TI - [Not Available]. PMID- 27370825 TI - [Not Available]. PMID- 27370828 TI - [Not Available]. PMID- 27370827 TI - [Not Available]. PMID- 27370829 TI - [Not Available]. PMID- 27370831 TI - [Not Available]. PMID- 27370830 TI - [Not Available]. PMID- 27370832 TI - [Not Available]. PMID- 27370833 TI - [Not Available]. PMID- 27370835 TI - [Not Available]. PMID- 27370834 TI - [Not Available]. PMID- 27370836 TI - [Not Available]. PMID- 27370837 TI - [Not Available]. PMID- 27370838 TI - [Not Available]. PMID- 27370839 TI - [Not Available]. PMID- 27370840 TI - [Not Available]. PMID- 27370842 TI - [Not Available]. PMID- 27370841 TI - [Not Available]. PMID- 27370843 TI - [Not Available]. PMID- 27370844 TI - [Not Available]. PMID- 27370845 TI - [Not Available]. PMID- 27370846 TI - [Not Available]. PMID- 27370847 TI - [Not Available]. PMID- 27370848 TI - [Not Available]. PMID- 27370849 TI - [Not Available]. PMID- 27370851 TI - [Not Available]. PMID- 27370850 TI - [Not Available]. PMID- 27370852 TI - [Not Available]. PMID- 27370853 TI - [Not Available]. PMID- 27370854 TI - [Not Available]. PMID- 27370855 TI - [Not Available]. PMID- 27370857 TI - [Not Available]. PMID- 27370856 TI - [Not Available]. PMID- 27370858 TI - [Not Available]. PMID- 27370859 TI - [Not Available]. PMID- 27370860 TI - [Not Available]. PMID- 27370861 TI - [Not Available]. PMID- 27370863 TI - [Not Available]. PMID- 27370862 TI - [Not Available]. PMID- 27370864 TI - [Not Available]. PMID- 27370865 TI - [Not Available]. PMID- 27370866 TI - [Not Available]. PMID- 27370867 TI - [Not Available]. PMID- 27370868 TI - [Not Available]. PMID- 27370869 TI - [Not Available]. PMID- 27370870 TI - [Not Available]. PMID- 27370872 TI - [Not Available]. PMID- 27370871 TI - [Not Available]. PMID- 27370873 TI - [Not Available]. PMID- 27370874 TI - [Not Available]. PMID- 27370875 TI - [Not Available]. PMID- 27370876 TI - [Not Available]. PMID- 27370877 TI - Widespread Pain and Low Widespread Pain Index Scores among Fibromyalgia-positive Cases Assessed with the 2010/2011 Fibromyalgia Criteria. AB - OBJECTIVE: Widespread pain is no longer required for fibromyalgia (FM) diagnosis according to the American College of Rheumatology (ACR) 2010 preliminary diagnostic criteria and its 2011 modification, but its absence may be of concern. We investigated whether the widespread pain definition was satisfactory and the consequences of having a small number of painful regions or of not satisfying the widespread pain criterion. METHODS: We studied 5011 patients who satisfied the 2011 criteria. FM was identified using the Widespread Pain Index (WPI) and the Symptom Severity Scale (SSS): WPI >= 7 and SSS >= 5 or WPI 3-6 and SSS >= 9. Widespread pain was 4 quadrants plus axial pain, according to the 1990 ACR FM criteria. RESULTS: There were 4700 patients (93.8%) who satisfied the ACR 1990 widespread pain criterion. Using a new strict definition for 5 pain regions based on the WPI sites, a modified widespread pain criterion requiring 4 of 5 regions identified 98.8% of criteria-positive patients. Patients without widespread pain or those in the low WPI/high SSS group had milder FM and no evidence of increased psychological or physical distress. CONCLUSION: In usual clinical and epidemiological studies, the 2011 and 2010 criteria work well, but are not as effective in patients with asymmetrical or regional pain who do not satisfy a widespread pain criterion. A >= 4-pain region widespread pain definition will eliminate regional pain false-positives and will identify 98.8% of current 2011 cases. Future revisions of the 2010/2011 criteria should consider incorporating the >= 4-region requirement to avoid misclassification. PMID- 27370878 TI - An Open-label, Phase II Study of the Safety and Tolerability of Pirfenidone in Patients with Scleroderma-associated Interstitial Lung Disease: the LOTUSS Trial. AB - OBJECTIVE: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) shares a number of clinical features and pathogenic mechanisms with idiopathic pulmonary fibrosis (IPF). This study was designed to evaluate the tolerability of the IPF treatment pirfenidone in SSc-ILD. The known gastrointestinal, skin, and liver adverse events (AE) of pirfenidone are of importance given the involvement of these organs in SSc. METHODS: All patients received pirfenidone and were randomized 1:1 to either a 2- or 4-week titration starting at 801 mg/day and finishing at a maintenance dose of 2403 mg/day. Patients received pirfenidone for 16 weeks in total. Assessments included treatment-emergent AE (TEAE) and exploratory disease outcomes. RESULTS: Sixty-three patients were randomized; 96.8% experienced a TEAE and more patients reported TEAE during the titration versus the maintenance period. The most commonly reported TEAE were consistent with those observed for pirfenidone in IPF (nausea, headache, fatigue) and were similar regardless of titration schedule. More patients discontinued treatment because of TEAE in the 2- versus 4-week titration group (5 vs 1, respectively); all discontinuation events occurred > 3 weeks after reaching the full dose of pirfenidone. Mycophenolate mofetil (MMF), taken by 63.5% of patients in addition to pirfenidone, did not appear to affect tolerability. Exploratory disease outcomes remained largely unchanged. CONCLUSION: Pirfenidone showed an acceptable tolerability profile in SSc-ILD, although a longer titration may be associated with better tolerability. Tolerability was not affected by concomitant MMF. The present findings support further investigation of pirfenidone in future clinical trials in patients with SSc-ILD. TRIAL REGISTRATION: ClinicalTrials.gov; www.clinicaltrials.gov NCT01933334. PMID- 27370880 TI - Risk of Serious Infection for Patients with Systemic Lupus Erythematosus Starting Glucocorticoids with or without Antimalarials. AB - OBJECTIVE: To compare serious infection risk for systemic lupus erythematosus (SLE) patients starting glucocorticoids (GC), antimalarials (AM), or their combination. METHODS: We conducted a new-user, historical cohort study, Kaiser Permanente Northern California, 1997-2013. Cox proportional hazards analysis was used to calculate adjusted HR and 95% CI. RESULTS: The study included 3030 patients with SLE followed an average of 4 years. Compared with patients starting AM without GC (9 infections/1461 patient-yrs), the HR for the risk of infection was 3.9 (95% CI 1.7-9.2) for those starting GC <= 15 mg/day without AM (14 infections/252 patient-yrs), while it was 0.0 (0 infections/128 patient-yrs) for those starting the combination. We split the 14 patients with a serious infection and with GC < 15 mg/day into 2 groups: < 7.5 and >= 7.5-15 mg/day. The HR for < 7.5 mg/day was 4.6 (95% CI 1.8-11.4) and for >= 7.5-15 mg/day, 3.1 (95% CI 1.0 9.7). For patients starting GC > 15 mg/day (reflecting more severe SLE), the risk of infection was nearly the same for the combination of GC and AM (9 infections/135 patient-yrs) and GC alone (41 infections/460 patient-yrs), but the combination users had evidence of more severe disease. Patients with SLE had a 6- to 7-fold greater risk of serious infection than the general population. CONCLUSION: Our findings suggest that the benefits of AM treatment for SLE may extend to preventing serious infections. Although the study included > 3000 patients, the statistical power to examine GC dosages < 15 mg/day was poor. PMID- 27370879 TI - Involvement of Mucosal-associated Invariant T cells in Ankylosing Spondylitis. AB - OBJECTIVE: Ankylosing spondylitis (AS) is characterized by chronic inflammation of the axial and peripheral joints and ligamentous attachments. Gut immunity is thought to be involved in AS, because a prominent coexistence of gut and joint inflammation has been observed in patients with AS. Mucosal-associated invariant T (MAIT) cells are preferentially located in the gut lamina propria and produce inflammatory cytokines such as interleukin 17 (IL-17) and tumor necrosis factor alpha (TNF-alpha), which are therapeutic targets for AS. This study aimed to investigate the involvement of MAIT cells in AS. METHODS: The frequency of MAIT cells and their cytokine production were determined in patients with AS and healthy controls (HC). The expression of a MAIT cell activation marker (CD69) was analyzed in patients with AS by using flow cytometry. RESULTS: The frequency of MAIT cells in the peripheral blood was lower in patients with AS compared with HC. The levels of IL-17 produced by MAIT cells after activation were higher in patients with AS than in the HC. CD69 expression on MAIT cells correlated with the Ankylosing Spondylitis Disease Activity Score in patients with AS. CONCLUSION: These results suggest the involvement of MAIT cells in the pathogenesis of AS. PMID- 27370881 TI - ACR/EULAR Definitions of Remission Are Associated with Lower Residual Inflammatory Activity Compared with DAS28 Remission on Hand MRI in Rheumatoid Arthritis. AB - OBJECTIVE: To determine the level of residual inflammation [synovitis, bone marrow edema (BME), tenosynovitis, and total inflammation] quantified by hand magnetic resonance imaging (h-MRI) in patients with rheumatoid arthritis (RA) in remission according to 3 different definitions of clinical remission, and to compare these remission definitions. METHODS: A cross-sectional study. To assess the level of residual MRI inflammation in remission, cutoff levels associated to remission and median scores of MRI residual inflammatory lesions were calculated. Data from an MRI register of patients with RA who have various levels of disease activity were used. These were used for the analyses: synovitis, BME according to the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system, tenosynovitis, total inflammation, and disease activity composite measures recorded at the time of MRI. Receiver-operating characteristic analysis was used to identify the best cutoffs associated with remission for each inflammatory lesion on h-MRI. Median values of each inflammatory lesion for each definition of remission were also calculated. RESULTS: A total of 388 h-MRI sets of patients with RA with different levels of disease activity, 130 in remission, were included. Cutoff values associated with remission according to the Simplified Disease Activity Index (SDAI) <= 3.3 and the Boolean American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) definitions for BME and tenosynovitis (1 and 3, respectively) were lower than BME and tenosynovitis (2 and 5, respectively) for the Disease Activity Score on 28 joints (DAS28) <= 2.6. Median scores for synovitis, BME, and total inflammation were also lower for the SDAI and Boolean ACR/EULAR remission criteria compared with DAS28. CONCLUSION: Patients with RA in remission according to the SDAI and Boolean ACR/EULAR definitions showed lower levels of MRI-detected residual inflammation compared with DAS28. PMID- 27370882 TI - Overestimation of femoral tunnel length during anterior cruciate ligament reconstruction using the retrograde outside-in drilling technique. AB - PURPOSE: When the femoral tunnel socket is reamed in an oblique direction from the wall of inter-condylar notch in anterior cruciate ligament (ACL) reconstruction, the tunnel length can be shorter at the periphery than at the centre. Because surgeons can manipulate the direction of tunnel in the outside-in femoral tunnel drilling technique, this length mismatch would vary depending on the direction of the tunnel. The purpose of this study was to investigate this length mismatch when reamed in various directions. METHODS: In total of thirteen points were defined as femoral drilling entry points on concentric lines with 0, 1, 2, and 3 cm radius from the lateral epicondyle of a three-dimensional bone model from 40 subjects. Femoral tunnel drilling was simulated on the models by connecting the centre of the ACL footprint with each defined point on the lateral femoral surface. The mismatch length was measured between the centre and the shortest peripheral side of the tunnel socket. RESULTS: When the distance between the drilling entry point on the lateral femoral surface and the lateral epicondyle was increased to anterior proximal direction, there was a significant increase in the mismatch length. The mismatch length became more than 2 mm when the entry point was located more than 2 cm away from the lateral epicondyle. CONCLUSIONS: When the drilling entry point is set far away from the lateral epicondyle, a significant increase was observed in tunnel length mismatch between the centre of the tunnel and its shortest peripheral side. Because the tunnel length is measured with a guide pin introduced at the centre of the tunnel before reaming in retrograde outside-in technique, this length mismatch could cause an overestimation of the tunnel length. Surgeons should recognise this mismatch when preparing the length of graft and socket to optimise the graft insertion length into the socket. PMID- 27370883 TI - Knee salvage in revision arthroplasty after massive bone loss of the femur condyles (>=Engh III) with a single-modular-hinged knee revision implant. AB - PURPOSE: Massive bone loss of the femur condyles in revision arthroplasty often requires modular-hinged revision implants to restore a stable joint situation. In the present series, the outcome after knee revision surgery using a single modular-hinged revision implant in patients with severe bone defects (>Engh III) is investigated. METHODS: Sixty patients with severe bone defects (>=Engh III) after failed primary and revision knee arthroplasty were included. Medium follow up was 47 (range 10-84) months after knee revision surgery. Medium patient age was 70 (range 33-87) years at the time of surgery. An average of 2.3 prior knee operations per patient was performed. 70 % of the patients required the knee revision implant after two-stage revision because of a deep implant infection. RESULTS: Estimated 5 year extremity survival was 95 and 65 % implant survival. Reasons for implant revision in decreasing order were reinfection (30 %), aseptic loosening (13 %), and periprosthetic fracture (9.8 %). The average active range of motion in the knee joint was 88 degrees (range 40 degrees -115 degrees ) for flexion. An extension deficit of a mean of -6 degrees was (range -50-5 degrees hyper-extension) observed. Patient age influenced the functional results significantly in terms of reduced walking distances and decreased modified WOMAC score. CONCLUSION: In consideration of this complex study, population acceptable functional results can be achieved using a modular knee revision endoprosthesis. In younger patients (<60 years), satisfying results in terms of walking ability and overall satisfactory can be expected. The outcome in older multimorbid patients is worse. Yet, operation in these patients can be feasible to restore enough mobility for daily household activities. PMID- 27370884 TI - [Not Available]. PMID- 27370885 TI - [Not Available]. PMID- 27370886 TI - [Not Available]. PMID- 27370887 TI - [Not Available]. PMID- 27370888 TI - [Not Available]. PMID- 27370890 TI - [Not Available]. PMID- 27370889 TI - [Not Available]. PMID- 27370891 TI - [Not Available]. PMID- 27370892 TI - Analgesic effect of a single dose of betamethasone after ambulatory knee arthroscopy: a randomized controlled trial. AB - PURPOSE: Glucocorticoids are reported to improve postoperative analgesia. The purpose of the study was to investigate whether a preoperative, single dose of betamethasone could reduce pain after ambulatory arthroscopic knee surgery. METHODS: This was a randomized, double-blind, placebo-controlled trial including patients scheduled for knee arthroscopy. The intervention was an intravenous injection of betamethasone 8 mg or placebo. The primary outcome was pain day 1 evaluated by a verbal descriptor scale (VDS). RESULTS: In total, 74 patients (betamethasone = 34; placebo = 40) were randomized. One patient in each group was excluded from analysis. During activity day 1 following surgery, the proportion with no or minor pain was significantly (p = 0.030) higher in the betamethasone group (22 of 33; 67 %) compared with the placebo group (17 of 39; 44 %). At rest, the corresponding figures were 26 of 33 (79 %) for betamethasone and 24 of 39 (62 %) for placebo (p = 0.062). After 3 months of follow-up, no patient receiving betamethasone experienced adverse events while six receiving placebo did (postoperative nausea and vomiting in five and delayed wound healing in one). CONCLUSIONS: An analgesic benefit was seen day 1 following surgery. This indicates that betamethasone has a place in ambulatory arthroscopic knee surgery. TRIAL REGISTRATION: https://www.clinicaltrialsregister.eu/ (identifier 2009 014717-27). PMID- 27370893 TI - Roles of endotracheal tubes and slip joints in respiratory pressure loss: a laboratory study. AB - PURPOSE: The endotracheal tube (ETT) constitutes a significant component of total airway resistance. However, a discrepancy between measured and theoretical values has been reported in airway resistance through ETTs. The causes of the discrepancy were estimated by physical and rheological simulations. METHODS: The pressure losses through total lengths of ETTs and slip joints under a volumetric flow rate of 30 L/min were measured, and the pressure losses through the tubular parts of ETTs with internal diameters (IDs) of 6.0-, 6.5-, 7.0-, 7.5-, and 8.0 mm were measured. The Reynolds number of each setting was calculated, and the pressure losses through the total length of the ETT, the tubular part, and the slip joint of each size of tube were estimated. RESULTS: The Reynolds numbers were >5000 in all sizes of ETTs. Measured pressure losses were larger in small sized ETTs than in large sized ETTs-520.9 Pascals (Pa) in 6.0-mm ID and 136.4 Pa in 8.0-mm ID tubes. The measured pressure losses through the tubular part were comparable to the predicted values. The measured pressure losses through the slip joints were larger than the predicted values, and they accounted for approximately 25-40% of total pressure losses of the ETTs. CONCLUSION: Especially in small sized tubes, the pressure loss through the slip joint accounts for a large percentage of the total pressure loss through the ETT. The pressure loss through the slip joint may play a role in the discrepancy between measured and theoretical pressure losses through ETTs. PMID- 27370895 TI - Microsatellite instability is associated with reduced disease specific survival in stage III colon cancer. AB - BACKGROUND: Up to 15% of colorectal cancers exhibit microsatellite instability (MSI), where errors in replication go unchecked due to defects in the mismatch repair system. This study aimed to determine survival in a large single-centre series of 1250 consecutive colorectal cancers subjected to universal MSI testing. METHODS: Clinical and pathological features of patients with colorectal cancer identified on prospectively maintained colorectal and pathology databases at St. Vincent's University Hospital from 2004 to May 2012 were examined. Mismatch repair (MMR) status was determined by immunohistochemistry. Kaplan-Meier curves, the log-rank test and Cox regression were used to associate survival with clinical and pathological characteristics. RESULTS: Of the 1250 colorectal cancers in the study period, 11% exhibited MSI (n = 138). Patients with MSI tumours had significantly lower rates of lymph node and distant metastases (MSI N+ rate: 24.8% compared with MSS N+ rate: 46.2%, p < 0.001). For Stage I and II disease MSI was associated with improved disease free survival (DSS) compared with MSS colon cancer. However, patients with Stage III MSI colon cancers had a worse DSS than those with MSS tumours. Stage III MSI tumours exhibited higher rates of lymphovascular invasion and perineural invasion than Stage I/II MSI tumours. CONCLUSION: MSI is associated with a reduced risk of nodal and distant metastases, with an improved DSS in Stage I/II colon cancer. However, when MSI tumours progress to Stage III these patients had worse outcomes and pathological features. New strategies for this cohort of patients may be required to improve outcomes. PMID- 27370896 TI - Relapse of both small cell lung cancer and Lambert-Eaton myasthenic syndrome after a 13-year disease-free survival period. AB - Lambert-Eaton myasthenic syndrome (LEMS) is a paraneoplastic syndrome and only 3% of small cell lung carcinoma (SCLC) patients have LEMS. Moreover, the recurrence of SCLC after a disease-free survival (DFS) of more than 10 years is rare. We report a patient who had a recurrence of both SCLC and LEMS after a 13-year DFS period. A 69-year-old man was diagnosed with LEMS and SCLC (cT0N2M0, stage IIIA) 13 years ago. Chemoradiotherapy was performed and a complete response was achieved. With anticancer treatment, the LEMS symptoms was alleviated. At the age of 82 years, gait disturbance appeared followed by left supraclavicular lymphadenopathy and further examination revealed the recurrence of SCLC. Careful screening for the recurrence of SCLC might be needed when the patient has recurrent or secondary paraneoplastic neurological syndrome even after a long DFS period. PMID- 27370894 TI - Combined effects of age and polymorphisms in Notch3 in the pathogenesis of cerebral infarction disease. AB - Cerebral infarction disease is a severe hypoxic ischemic tissue necrosis in the brain, often leading to long-term functional disability and residual impairments. The Notch signaling pathway plays key roles in proliferation and survival of the stem/progenitor cells of the central and peripheral nervous systems. Notch3 is an important member of the pathway, but the relationships between the genetic abnormalities and cerebral infarction disease still remain unclear. The aim of this work was to evaluate variations in Notch3 gene for their possible associations with the cerebral infarction disease. We sequenced the Notch3 gene for 260 patients with cerebral infarction disease, 300 normal controls with old ages and 300 normal controls with younger ages, and identified the variations. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 19.0). The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE. Six variations, including rs1044116, rs1044009, rs1044006, rs10408676, rs1043996 and rs16980398 within or near the Notch3 gene, were found. The genetic heterozygosity of rs1044116, rs1044009, rs1044006, and rs1043996 was very high, whereas that of rs10408676 and rs16980398 was very low. Statistical analyses showed that rs1044009 and rs1044006 were associated with the risk of cerebral infarction disease in the Chinese Han agedness population. The SNPs rs1044009 and rs1044006 in the Notch3 gene were associated with the risk of cerebral infarction diseases in the Chinese Han agedness population. PMID- 27370897 TI - [Tolerance of bevacizumab therapy in systemic sclerosis-associated pulmonary arterial hypertension: A case report]. AB - INTRODUCTION: No data is available regarding the safety of bevacizumab, an anti vascular endothelial growth factor-A (VEGF-A) antibody, in patients with pulmonary arterial hypertension (PAH), a condition in which VEGF seems to play a significant and probably protective role. CASE REPORT: We report a patient with a history of systemic sclerosis-associated PAH, stable under bosentan therapy. She was diagnosed with metastatic cervical epidermoid carcinoma and treated by two successive cytotoxic chemotherapy regimens. As these treatments failed to control disease progression, she was started on anti-angiogenic therapy: 3 infusions of bevacizumab 15 mg/kg were administered. Over the course of this treatment, no change in the clinical status or echocardiography parameters was noted. CONCLUSION: This observation suggests that, under careful clinical and echocardiographic follow-up, bevacizumab therapy can be well tolerated in case of stable and moderate PAH. Decision of treatment should be taken cautiously, as the possibility of PAH worsening is not excluded. PMID- 27370898 TI - [Cancer immunotherapy: Rational and recent breakthroughs]. AB - Cancer immunotherapy has occupied a marginal therapeutic option in cancer despite strong arguments documenting the role of the immune system in controlling the proliferation of cancers. The recent success of immunotherapy results from a change in the past paradigm. From now on, the goal is not only to activate the immune system against tumor, but also to take account of the immunosuppressive tumor microenvironment Among these mechanisms, negative costimulatory molecules (CTLA-4, PD-1, etc.) expressed by T cells in the tumor could explain their lack of effectiveness in inhibiting tumor growth. Blocking these molecules allowed the reactivation of anti-tumor T cells. Clinically, the administration of anti-CTLA-4 antibody (ipilimumab: Yervoy(r)) was granted marketing authorization for patients with metastatic melanoma. The anti-PD-1 antibodies (nivolumab: Opdivo(r), pembrolizumab: Keytruda(r)) have demonstrated clinical efficacy when compared to the standard therapy in metastatic melanomas, advanced lung cancers and metastatic renal cell carcinoma. In phase I and II clinical trials, other tumors (Hodgkin's disease, head and neck cancers, bladder cancer, gastric cancer, etc.) appear to be responsive to these immunomodulators. These treatments were associated with the occurrence of side effects dominated by autoimmunity predictable by unlocking the breaks exerted by immune system to maintain tolerance against self-antigen. The optimization of therapeutic combination based on these molecules and the search for biomarkers associated with these treatments constitute a challenge for the future for this new therapeutic class of drugs for oncology. PMID- 27370899 TI - A genome-wide association analysis of chromosomal aberrations and Hirschsprung disease. AB - Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of intramural ganglion cells along variable lengths of the gastrointestinal tract. Although the RET proto-oncogene is considered to be the main risk factor for HSCR, only about 30% of the HSCR cases can be explained by variations in previously known genes including RET. Recently, copy number variation (CNV) and loss of heterozygosity (LOH) have emerged as new ways to understand human genomic variation. The goal of this present study is to identify new HSCR genetic factors related to CNV in Korean patients. In the genome-wide genotyping, using Illumina's HumanOmni1-Quad BeadChip (1,140,419 markers), of 123 HSCR patients and 432 unaffected subjects (total n = 555), a total of 8,188 CNVs (1 kb ~ 1 mb) were identified by CNVpartition. As a result, 16 CNV regions and 13 LOH regions were identified as associated with HSCR (minimum P = 0.0005). Two top CNV regions (deletions at chr6:32675155-32680480 and chr22:20733495-21607293) were successfully validated by additional real-time quantitative polymerase chain reaction analysis. In addition, 2 CNV regions (6p21.32 and 22q11.21) and 2 LOH regions (3p22.2 and 14q23.3) were discovered to be unique to the HSCR patients group. Regarding the large-scale chromosomal aberrations (>1 mb), 11 large aberrations in the HSCR patients group were identified, which suggests that they may be a risk factor for HSCR. Although further replication in a larger cohort is needed, our findings may contribute to the understanding of the etiology of HSCR. PMID- 27370900 TI - Retinal image registration under the assumption of a spherical eye. AB - We propose a method for registering a pair of retinal images. The proposed approach employs point correspondences and assumes that the human eye has a spherical shape. The image registration problem is formulated as a 3D pose estimation problem, solved by estimating the rigid transformation that relates the views from which the two images were acquired. Given this estimate, each image can be warped upon the other so that pixels with the same coordinates image the same retinal point. Extensive experimental evaluation shows improved accuracy over state of the art methods, as well as robustness to noise and spurious keypoint matches. Experiments also indicate the method's applicability to the comparative analysis of images from different examinations that may exhibit changes and its applicability to diagnostic support. PMID- 27370901 TI - Biomarkers of kidney function and prediction of death from cardiovascular and other causes in the elderly: A 9-year follow-up study. AB - BACKGROUND: Cystatin C is claimed to be superior to creatinine-based estimates of glomerular filtration rate (eGFRcr). The purpose of the study is to analyze whether cystatin C, creatinine, and/or estimated glomerular filtration rates (eGFR) predicted cardiovascular and/or non-cardiovascular deaths among Finnish elderly. METHODS: Hazard ratios (HR) of cystatin C, creatinine and eGFRs for cardiovascular and non-cardiovascular deaths. RESULTS: During a 9-year follow-up, 275 died, 192 deaths were a result of cardiovascular disease. In age-adjusted analyses, cystatin C predicted the risk of non-cardiovascular and cardiovascular death in men (HR for 0.1-unit increase 1.12 [95% CI, 1.04-1.19] for non-CVD deaths and 1.18 [1.09-1.28] for CVD deaths) and women (1.14 [1.07-1.21] and 1.14 [1.06-1.22], respectively). CKD-EPIcr-cyc predicted the risk of CVD deaths in men (HR for 5-unit decrease 1.17 [1.09-1.25]) and women (1.09 [1.02-1.17]) and non CVD deaths in women (1.07 [1.01-1.14]). Also, MDRD (HR for 5-unit decrease 1.16 [1.05-1.27]) and CKD-EPI (HR for 5-unit decrease 1.15 [1.05-1.25]) predicted CVD deaths among men. After additional adjustments, predictive value of cystatin C remained significant. Also, the predictive value of CKD-EPIcr-cys remained significant in non-CVD deaths among women. CONCLUSION: Cystatin C was clearly the best predictor for cardiovascular and non-cardiovascular deaths among Finnish elderly. Serum cystatin C is more accurate for clinical decision making than creatinine-based eGFR equations or the combined CKD-EPIcr-cys equation in persons older than 64years. PMID- 27370902 TI - Reclassification of Clostridium difficile as Clostridioides difficile (Hall and O'Toole 1935) Prevot 1938. AB - The recent proposal by Lawson and Rainey (2015) to restrict the genus Clostridium to Clostridium butyricum and related species has ramifications for the members of the genera that fall outside this clade that should not be considered as Clostridium sensu stricto. One such organism of profound medical importance is Clostridioides difficile that is a major cause of hospital-acquired diarrhea and mortality in individuals. Based on 16S rRNA gene sequence analysis, the closest relative of Clostridium difficile is Clostridium mangenotii with a 94.7% similarity value and both are located within the family Peptostreptococcaceae that is phylogenetically far removed from C. butyricum and other members of Clostridium sensu stricto. Clostridium difficile is Clostridium mangenotii each produce abundant H2 gas when grown in PYG broth and also produce a range of straight and branched chain saturated and unsaturated fatty acids with C16:0 as a major product. The cell wall peptidoglycan contains meso-DAP as the diagnostic diamino acid. Based on phenotypic, chemotaxonomic and phylogenetic analyses, novel genus Clostridioides gen. nov. is proposed for Clostridium difficile as Clostridioides difficile gen. nov. comb. nov. and that Clostridium mangenotii be transferred to this genus as Clostridioides mangenotii comb. nov. The type species of Clostridioides is Clostridioides difficile. PMID- 27370903 TI - Climate change impacts and adaptive strategies: lessons from the grapevine. AB - The cultivation of grapevines for winemaking, known as viticulture, is widely cited as a climate-sensitive agricultural system that has been used as an indicator of both historic and contemporary climate change. Numerous studies have questioned the viability of major viticulture regions under future climate projections. We review the methods used to study the impacts of climate change on viticulture in the light of what is known about the effects of climate and weather on the yields and quality of vineyard harvests. Many potential impacts of climate change on viticulture, particularly those associated with a change in climate variability or seasonal weather patterns, are rarely captured. Key biophysical characteristics of viticulture are often unaccounted for, including the variability of grapevine phenology and the exploitation of microclimatic niches that permit successful cultivation under suboptimal macroclimatic conditions. We consider how these same biophysical characteristics permit a variety of strategies by which viticulture can adapt to changing climatic conditions. The ability to realize these strategies, however, is affected by uneven exposure to risks across the winemaking sector, and the evolving capacity for decision-making within and across organizational boundaries. The role grape provenance plays in shaping perceptions of wine value and quality illustrates how conflicts of interest influence decisions about adaptive strategies within the industry. We conclude by considering what lessons can be taken from viticulture for studies of climate change impacts and the capacity for adaptation in other agricultural and natural systems. PMID- 27370904 TI - Design and properties of 3D scaffolds for bone tissue engineering. AB - In this study, the Voronoi tessellation method has been used to design novel bone like three dimension (3D) porous scaffolds. The Voronoi method has been processed with computer design software to obtain 3D virtual isotropic porous interconnected models, exactly matching the main histomorphometric indices of trabecular bone (trabecular thickness, trabecular separation, trabecular number, bone volume to total volume ratio, bone surface to bone volume ratio, etc.). These bone like models have been further computed for mechanical (elastic modulus) and fluid mass transport (permeability) properties. The results show that the final properties of the scaffolds can be controlled during their microstructure and histomorphometric initial design stage. It is also shown that final properties can be tuned during the design stage to exactly match those of trabecular natural bone. Moreover, identical total porosity models can be designed with quite different specific bone surface area and thus, this specific microstructural feature can be used to favour cell adhesion, migration and, ultimately, new bone apposition (i.e. osteoconduction). Once the virtual models are fully characterized and optimized, these can be easily 3D printed by additive manufacturing and/or stereolitography technologies. STATEMENT OF SIGNIFICANCE: The significance of this article goes far beyond the specific objectives on which it is focussed. In fact, it shows, in a guided way, the entire novel process that can be followed to design graded porous implants, whatever its external shape and geometry, but internally tuned to the exact histomorphometric indices needed to match natural human tissues microstructures and, consequently, their mechanical and fluid properties, among others. The significance is even more relevant nowadays thanks to the available new computing and design software that is easily linked to the 3D printing new technologies. It is this transversality, at the frontier of different disciplines, the main characteristic that gives this article a high scientific impact and interest to a broaden audience. PMID- 27370905 TI - Functionalized cell nucleus-penetrating peptide combined with doxorubicin for synergistic treatment of glioma. AB - Clinical application of cell-penetrating peptides (CPPs) in cancer therapy is greatly restricted due to lack of tissue selectivity and tumor-targeting ability. CB5005, a rationally designed CPP that targets and inhibits intracellular NF kappaB activation, is constituted by a unique membrane-permeable sequence (CB5005M) cascading to a NF-kappaB nuclear localization sequence (CB5005N). In vitro cellular evaluation confirmed that CB5005 was effectively taken up by brain capillary endothelial cell bEnd.3 and glioma cells U87. The intracellular localization analysis further demonstrated that CB5005 could not only penetrate into the cells but also enter into their nuclei. More interestingly, CB5005 permeated deeply into the tumor spheroids of U87 cell. In vivo imaging illustrated that the fluorescence-labeled CB5005 distributed itself into the brain and accumulated at the tumor site after intravenous injection. Given the important role of over expressed NF-kappaB in tumor growth and development, we further investigated CB5005 for its potential in treatment of glioma. When combined administration in vitro with doxorubicin (DOX), CB5005 exhibited a synergistic effect in killing U87 cells. In a nude mice xenograft model, CB5005 inhibited the growth of tumor when applied alone, and displayed a synergistic anti-tumor effect with DOX. In conclusion, CB5005 functioned simultaneously as a cell penetrating peptide and a tumor growth inhibitor, therefore can work as a potential synergist for chemotherapy of human tumor. STATEMENT OF SIGNIFICANCE: Clinical application of cell-penetrating peptides in cancer therapy is restricted due to lack of tissue selectivity and tumor-targeting ability. In this manuscript, we reported a rationally designed peptide, named CB5005, which had an attractive capability of translocation into the cell nucleus and blocking nuclear translocation of endogenous NF-kappaB protein. CB5005 had unique affinity with brain and glioma, and could rapidly accumulate in these tissues after intravenous injection. Furthermore, CB5005 showed a synergistic effect on inhibiting gliomas when administrated with doxorubicin. This is the first literature report on this multi-functionalized peptide, which can work as a potential synergist for chemotherapy of tumor. This work should be of general interest to scientists in the fields of biomaterials, biology, pharmacy, and oncology. PMID- 27370906 TI - A newly identified mechanism involved in regulation of human mesenchymal stem cells by fibrous substrate stiffness. AB - Stiffness of biomaterial substrates plays a critical role in regulation of cell behavior. Although the effect of substrate stiffness on cell behavior has been extensively studied, molecular mechanisms of regulation rather than those involving cytoskeletal activities still remain elusive. In this study, we fabricated aligned ultrafine fibers and treated the fiber with different annealing temperatures to produce fibrous substrates with different stiffness. Human mesenchymal stem cells (hMSCs) were then cultured on these fibrous substrates. Our results showed that annealing treatment did not change the diameter of electrospun fibers but increased their polymer crystallinity and mechanical properties. The mRNA expression of RUNX2 was upregulated while the mRNA expression of scleraxis was downregulated in response to an increase in substrate stiffness, suggesting that increased stiffness favorably drives hMSCs into the osteogenic lineage. With subsequent induction of osteogenic differentiation, osteogenesis of hMSCs on stiffer substrates was increased compared to that of the cells on control substrates. Cells on stiffer substrates increasingly activated AKT and YAP and upregulated transcript expression of YAP target genes compared to those on control substrates, and inhibition of AKT led to decreased expression of YAP and RUNX2. Furthermore, macrophage migration inhibitory factor (MIF) was increasingly produced by the cell on stiffer substrates, and knocking down MIF by siRNA resulted in decreased AKT phosphorylation. Taken together, we hereby demonstrate that simply using the annealing approach can manipulate stiffness of an aligned fibrous substrate without altering the material chemistry, and substrate stiffness dictates hMSC differentiation through the MIF-mediated AKT/YAP/RUNX2 pathway. STATEMENT OF SIGNIFICANCE: Stiffness of biomaterial substrates plays a critical role in regulation of cell behavior. Although the effect of substrate stiffness on cell behavior has been extensively studied, molecular mechanisms of regulation rather than those involving cytoskeletal activities still remain elusive. In this manuscript, we report our new findings that simply using the annealing approach can manipulate stiffness of an aligned fibrous substrate without altering the material chemistry, and substrate stiffness dictates human mesenchymal stem cell (hMSC) differentiation through the macrophage migration inhibitory factor mediated AKT/YAP/RUNX2 pathway. The findings are novel and interesting because we have identified a new mechanism rather than those involving cytoskeleton activity, by which substrate stiffness regulates hMSC behavior. PMID- 27370907 TI - Bioactive glass-based materials with hierarchical porosity for medical applications: Review of recent advances. AB - Bioactive glasses have been traditionally used in the clinical practice to fill and restore osseous defects due to their unique ability to bond to host bone and stimulate new bone growth. In the last decade, a new set of bioactive glasses characterized by a highly ordered mesoporous texture has been developed and studied as a smart platform for the controlled release of biomolecules, in situ therapy and regenerative applications. This review points out the great potential carried by hierarchical bioactive glass scaffolds that exhibit pore scales from the meso- to the macro-range, and their impact in the broad field of tissue engineering, including the emerging applications in contact with soft tissues and diagnostics. Recent advances in the preparation methods of these multiscale constructs (e.g. mono- or multi-phase scaffolds, fibrous meshes, coated systems, porous nanospheres, and composites) are examined, along with their strengths and weaknesses. A bright future is expected for hierarchical systems based on biocompatible mesoporous materials as they can provide a unique set of functionalities, including enhanced bioactivity, local release of ions and drugs to elicit specific therapeutic effects (improved osteogenesis and angiogenesis, antibacterial properties), and implant/drug tracking, which were unthinkable when research on bioactive glasses began. STATEMENT OF SIGNIFICANCE: The advent of mesoporous bioactive glasses led to the birth of a new class of multifunctional biomaterials that have been proposed as smart platforms for local drug release and bone regeneration. Furthermore, mesoporous materials have been recently employed in the development of hierarchical macro-mesoporous scaffolds, composites and implantable systems. This reviews summarizes the latest applications of these multiscale biomaterials in tissue engineering, including the emerging applications in contact with soft tissues and diagnostics. The preparation methods, current uses and potential of these constructs and systems are examined and critically discussed to provide a useful, up-to-date contribution to the scientists working in the field. PMID- 27370909 TI - [Not Available]. PMID- 27370908 TI - Scrambler Therapy((r)) MC-5A for Complex Regional Pain Syndrome: Case Reports. AB - BACKGROUND: Complex regional pain syndrome (CRPS) is a disorder that is often challenging to treat and can be associated with a prolonged course of severe pain. Therapy of CRPS remains controversial; the pain often can be very difficult to control, and treatment includes medications, physical therapy, regional anesthesia, and neuromodulation. AIM: We evaluated Scrambler Therapy((r)) (ST) in terms of efficacy, safety, and durability of treatment effect in patients suffering from CRPS. MATERIALS AND METHODS: We report the response to ST in four patients with CRPS referred to the Pain Center of Bambino Gesu Children's Hospital. The patients previously did not respond to conventional and nonconventional medical treatments. RESULTS: The treatment with ST was found effective in all four of our patients; they obtained pain relief for long periods and an improvement in their quality of life. We observed a progressive improvement with complete disappearance of neuropathic pain. Patients also reported a muscle strength increase that allowed them to resume normal daily activities. DISCUSSION AND CONCLUSION: We conclude that ST may offer a therapeutic opportunity for patients with neuropathic pain resulting from CRPS, without side effects and with minimal discomfort during treatment. The observed pain relief indicates that ST could be an effective option for such patients. PMID- 27370910 TI - Acid-base interactions in amorphous solid dispersions of lumefantrine prepared by spray-drying and hot-melt extrusion using X-ray photoelectron spectroscopy. AB - This study investigates drug-excipient interactions in amorphous solid dispersions (ASDs) of the model basic compound lumefantrine (LMN), with five acidic polymers. X-ray photoelectron spectroscopy (XPS) was used to measure the extent of the protonation of the tertiary amine in LMN by the five acidic polymers. The extent/efficiency of protonation of the ASDs was assessed a function of polymer type, manufacturing process (hot-melt extrusion vs. spray drying), and drug loading (DL). The most strongly acidic polymer, polystyrene sulfonic acid (PSSA) was found to be the most efficient polymer in protonating LMN, independently of manufacturing method and DL. The rank order for the protonation extent of LMN by each polymer is roughtly the same for both manufacturing processes. However, protonation efficiency of polymers of similar acidic strength ranged from ~0% to 75% (HPMCAS and Eudragit L100-55, respectively), suggesting an important role of molecular/mixing effects. For some polymers, including Eudragit L100 55 and HPMCP, spray-drying resulted in higher protonation efficiency compared to hot-melt extrusion. This result is attributable to a more favorable encounter between acid and base groups, when exposed to each other in solution phase. Increasing DL led to decreased protonation efficiency in most cases, particularly for polyacrylic acid, despite having the highest content of acidic groups per unit mass. These results indicate that the combined effects of acid strength and mixing phenomena regulate the efficiency of acid-base interactions in the ASDs. PMID- 27370911 TI - Bactericidal effect of graphene oxide/Cu/Ag nanoderivatives against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus. AB - A systematic analysis of antibacterial activity of individual nanoderivatives, e.g. GO nanosheets, Ag and Cu nanoparticles (NPs), as well as combinations of Cu Ag NPs, and GO-Cu-Ag nanocomposites against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae and Methicillin resistant Staphylococcus aureus (MRSA) was performed. Chemical properties of the GO, Cu and Ag NPs were determined employing X-ray photoelectron spectroscopy and X-Ray-excited Auger electron spectroscopy. Morphology of corresponding nanoderivatives was studied employing transmission electron microscopy and scanning electron microscopy. It was shown that combination of Cu and Ag NPs, as well as GO-Cu-Ag nanocomposite material possess enhanced antibacterial activity through a possible synergy between multiple toxicity mechanisms. MRSA showed highest resistance in all cases. PMID- 27370912 TI - The effect of liver esterases and temperature on remifentanil degradation in vitro. AB - Remifentanil is a potent opioid metabolized by serum and tissue esterases; it is routinely administered to patients with liver failure as anaesthetic and analgo sedative without variation in doses, even if prolonged clinical effects and respiratory depression have been observed in these patients. The aim of this study was to determine remifentanil enzymatic degradation kinetics bearing in mind the effect of liver esterases in order to trace a more accurate pharmacokinetic profile of the drug. Solution samples were taken over time and analysed to measure remifentanil concentration by HPLC. We reproduced the physiological settings, varying temperature and pH in vitro and evaluated the kinetics of degradation of remifentanil in the presence of Rhizopus Oryzae esterases, equine liver esterases and porcine liver esterases. Remifentanil kinetics of degradation was accelerated by porcine liver esterases. Remifentanil in vitro half-life decreases with increasing temperatures in the presence of porcine liver esterases. A drug model simulation considering the effect of temperature in the presence of liver esterases was developed. Remifentanil in vitro half-life decreases with increasing temperatures when porcine liver esterases are present. In this paper we propose a model for describing remifentanil degradation kinetics at various temperatures. PMID- 27370913 TI - Single-Dose Oritavancin Treatment of Acute Bacterial Skin and Skin Structure Infections: SOLO Trial Efficacy by Eron Severity and Management Setting. AB - INTRODUCTION: Introduction of new antibiotics enabling single-dose administration, such as oritavancin may significantly impact site of care decisions for patients with acute bacterial skin and skin structure infections (ABSSSI). This analysis compared the efficacy of single-dose oritavancin with multiple-dose vancomycin in patients categorized according to disease severity via modified Eron classification and management setting. METHODS: SOLO I and II were phase 3 studies evaluating single-dose oritavancin versus 7-10 days of vancomycin for treatment of ABSSSI. Patient characteristics were collected at baseline and retrospectively analyzed. Study protocols were amended, allowing outpatient management at the discretion of investigators. In this post hoc analysis, patients were categorized according to a modified Eron severity classification and management setting (outpatient vs. inpatient) and the efficacy compared. RESULTS: Overall, 1910 patients in the SOLO trials were categorized into Class I (520, 26.5%), II (790, 40.3%), and III (600, 30.6%). Of the 767 patients (40%) in the SOLO trials who were managed entirely in the outpatient setting 40.3% were categorized as Class II and 30.6% were Class III. Clinical efficacy was similar between oritavancin and vancomycin treatment groups, regardless of severity classification and across inpatient and outpatient settings. Class III patients had lower response rates (oritavancin 73.3%, vancomycin 76.6%) at early clinical evaluation when compared to patients in Class I (82.6%) or II (86.1%); however, clinical cure rates at the post-therapy evaluation were similar for Class III patients (oritavancin 79.8%, vancomycin 79.9%) when compared to Class I and II patients (79.1-85.7%). CONCLUSION: Single dose oritavancin therapy results in efficacy comparable to multiple-dose vancomycin in patients categorized according to modified Eron disease severity classification regardless of whether management occurred in the inpatient or outpatient setting. FUNDING: The Medicines Company, Parsippany, NJ, USA. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT01252719 (SOLO I) and NCT01252732 (SOLO II). PMID- 27370915 TI - Medicine and democracy: The importance of institutional quality in the relationship between health expenditure and health outcomes in the MENA region. AB - Evidence suggests that the effect of health expenditure on health outcomes is highly context-specific and may be driven by other factors. We construct a panel dataset of 18 countries from the Middle East and North Africa region for the period 1995-2012. Panel data models are used to estimate the macro-level determinants of health outcomes. The core finding of the paper is that increasing health expenditure leads to health outcomes improvements only to the extent that the quality of institutions within a country is sufficiently high. The sensitivity of the results is assessed using various measures of health outcomes as well as institutional variables. Overall, it appears that increasing health care expenditure in the MENA region is a necessary but not sufficient condition for health outcomes improvements. PMID- 27370916 TI - Health sector employment growth calls for improvements in labor productivity. AB - While rising costs of healthcare have put increased fiscal pressure on public finance, job growth in the health sector has had a stabilizing force on overall employment levels - not least in times of economic crises. In 2014 EU-15 countries employed 21 million people in the health and social care sector. Between 2000 and 2014 the share of employed persons in this sector rose from 9.5% to 12.5% of the total labor force in EU-15 countries. Over time labor input growth has shifted towards residential care activities and social work while labor in human health activities including hospitals and ambulatory care still comprises the major share. About half of the human health labor force works in hospital. Variation of health and social care employment is large even in countries with generally comparable institutional structures. While standard measures of productivity in health and social care are not yet comparable across countries, we argue that labor productivity of a growing health work force needs more attention. The long-term stability of the health system will require care delivery models that better utilize a growing health work force in concert with smart investments in digital infrastructure to support this transition. In light of this, more research is needed to explain variations in health and social care labor endowments, to identify effective policy measures of labor productivity enhancement including enhanced efforts to develop comparable productivity indicators in these areas. PMID- 27370914 TI - Epidemiology and Risk Factors for Community-Associated Clostridium difficile Infection: A Narrative Review. AB - Clostridium difficile infection (CDI) was once considered a primarily nosocomial concern. Emerging evidence from the last 20 years has highlighted a drastic shift in the known epidemiology of CDI, with disease outside of hospitals apparently occurring more frequently and causing severe disease in populations that were thought to be at low risk. This narrative review summarises potential pathways for infection outside of the hospital environment and highlights likely routes of transmission. Further, evidence is presented on potential risk factors for development of disease. Understanding the epidemiology of CDI outside of hospitals is essential to the ability to prevent and control disease in vulnerable populations. PMID- 27370917 TI - Oncological Patient Anxiety in Imaging Studies: the PET/CT Example. AB - The purpose of this study was to investigate the subjective perception of anxiety pre- and post-procedure, and explore the relationship between demographic, clinical variables and cancer patients' anxiety during a positron emission tomography/computed tomography (PET/CT) scan. Two hundred and thirty-two oncological out patients, with clinical indication for performing an 18F-2-fluoro 2-deoxy-D-glucose (18F-FDG) PET/CT scan and attending a nuclear medicine (NM) department, participated in the study. Patients' anxiety and subjective experience of PET/CT were examined using two self-report questionnaires. The pre procedure questionnaire focused on demographic information, level of knowledge regarding the scan and subjective perception of anxiety before the procedure. The post-procedure questionnaire included the subjective perception anxiety after the procedure, information adequacy and satisfaction with the NM department. The self reported data indicate that patients were anxious during PET/CT. Furthermore, our data revealed a significant difference between the anxiety pre-procedure and post procedure (z = -3909, p < 0.05), in which the anxiety pre-procedure has significantly higher values. No significant correlation was found between anxiety and age of the patients, education levels, adequacy of information or satisfaction with the NM Department. Perception of anxiety post-procedure differs between gender (U = 5641, p = 0.033). In conclusion, PET/CT generated anxiety levels in oncological patients, especially before the procedure. Although patients seemed to be satisfied with information delivered by staff and with the NM Department, attention has to be focused on effective interventions strategies that help patients to reduce anxiety. PMID- 27370919 TI - [Not Available]. PMID- 27370920 TI - [Not Available]. PMID- 27370918 TI - A review of percutaneous transhepatic biliary drainage at a tertiary referral centre. AB - AIM: To review percutaneous biliary drainage (PBD) procedures performed in Beaumont Hospital, Dublin, Ireland, over a 6-year period, to determine the 30-day morbidity and mortality. MATERIALS AND METHODS: A total of 119 patients undergoing 193 PBD procedures were identified over a 6 year period. Of the patients, 6.7% (eight patients) had stone disease, 63% (75 patients) had a malignancy, and the remainder were diagnosed with other conditions. Standard techniques of PBD and biliary stent insertion were applied, with 73 patients (61%) having same-day procedures and all undergoing gelfoam embolisation of percutaneous tracts. All patients received intravenous prophylactic antibiotics and intravenous hydration prior to PBD. RESULTS: The technical success rate was 97%, with a mean drop of 105 mmol/l between pre- and post-procedure bilirubin. Thirty-day mortality was 10.9% (13 deaths), with major and minor morbidities of 5% (six patients) and 7.6% (nine patients), respectively. Major complications included sepsis in two patients, major haemorrhage in two patients, and renal failure in two patients. Minor complications included infection in seven patients, bile leak causing self-limiting pain in one patient, and minor haemorrhage in one patient. CONCLUSION: The study confirms that PBD and stent insertion is a safe and effective technique in Beaumont Hospital, associated with an overall acceptable morbidity and mortality comparable with other studies. PMID- 27370921 TI - [Not Available]. PMID- 27370922 TI - [Not Available]. PMID- 27370923 TI - [Not Available]. PMID- 27370924 TI - [Not Available]. PMID- 27370925 TI - [Not Available]. PMID- 27370926 TI - [Not Available]. PMID- 27370927 TI - [Not Available]. PMID- 27370928 TI - [Not Available]. PMID- 27370929 TI - [Not Available]. PMID- 27370930 TI - [Not Available]. PMID- 27370932 TI - [Not Available]. PMID- 27370931 TI - [Not Available]. PMID- 27370933 TI - [Not Available]. PMID- 27370934 TI - [Not Available]. PMID- 27370935 TI - [Not Available]. PMID- 27370936 TI - Expression of 14-3-3 transcript isoforms in response to ethanol exposure and their regulation by miRNAs. AB - The 14-3-3 proteins are a family of highly conserved molecular chaperones involved in the regulation of a number of key cellular functions including metabolism, stress response, protein trafficking, cell-cycle control, signal transduction, transcription, apoptosis and neurotransmission. 14-3-3 proteins have also been implicated in the pathophysiology of neurodegenerative disorders including Alzheimer disease and Parkinson disease. Recent studies have also shown that 14-3-3s are differentially expressed in the frontal cortex of human alcoholics suggesting a potential role in the pathophysiology of alcohol use disorders. Here we measured the expression of 14-3-3 transcripts in HEK293T cells in response to chronic ethanol treatment. Five of the seven transcripts (14-3 3beta, 14-3-3gamma, 14-3-3zeta, 14-3-3epsilon and 14-3-3theta) were significantly down-regulated following chronic exposure to ethanol for a five day period with these changes persisting even after withdrawal from ethanol treatment. One transcript, 14-3-3sigma, was significantly up-regulated following chronic ethanol exposure and 14-3-3eta showed no differences in expression in the same treatment model. The pattern of expression changes is similar to those seen in the frontal cortex of human alcoholics. To investigate the role of miRNAs in mediating the expression changes we measured the expression of the 14-3-3 transcripts following transfection with miR-203, miR-144 and miR-7 mimics. Although these miRNAs had predicted target sites in the 3'untranslated region of each 14-3-3 isoform, only miR-203 resulted in a down-regulation of 14-3-3theta transcript. In addition, the expression of 14-3-3gamma was upregulated following transfection with miR-7 and miR-144 mimics. MiRNA regulation of these isoforms following alcohol exposure may lead to alterations in neurotransmission, the balance between cell survival and cell death, as well as changing the rewarding effects of alcohol. PMID- 27370937 TI - An electrophysiological study on the effects of BDNF and FGF2 on voltage dependent Ca(2+) currents in developing human striatal primordium. AB - Over the past decades, studies in both Huntington's disease animal models and pilot clinical trials have demonstrated that replacement of degenerated striatum and repair of circuitries by grafting fetal striatal primordium is feasible, safe and may counteract disease progression. However, a better comprehension of striatal ontogenesis is required to assess the fetal graft regenerative potential. During neuronal development, neurotrophins exert pleiotropic actions in regulating cell fate and synaptic plasticity. In this regard, brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 2 (FGF2) are crucially implicated in the control of fate choice of striatal progenitor cells. In this study, we intended to refine the functional features of human striatal precursor (HSP) cells isolated from ganglionic eminence of 9-12week old human fetuses, by studying with electrophysiological methods the effect of BDNF and FGF2 on the membrane biophysical properties and the voltage-dependent Ca(2+) currents. These features are particularly relevant to evaluate neuronal cell functioning and can be considered reliable markers of the developmental phenotype of human striatal primordium. Our results have demonstrated that BDNF and FGF2 induced membrane hyperpolarization, increased the membrane capacitance and reduced the resting total and specific conductance values, suggesting a more efficient control of resting ionic fluxes. Moreover, the treatment with both neurotrophins enhanced N type Ca(2+) current amplitude and reduced L- and T-type ones. Overall, our data indicate that BDNF and FGF2 may help HSP cells to attain a more functionally mature phenotype. PMID- 27370938 TI - Neurochemical correlation between major depressive disorder and neurodegenerative diseases. AB - Major depressive disorder (MDD) is one of the most prevalent and life-threatening forms of mental illnesses affecting elderly people and has been associated with poor cognitive function. Recent evidence suggests a strong relationship between MDD and neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), as well as natural processes of aging. Changes in the neuroplasticity, morphology, and neurotransmission in the brain are seem to be associated to both, MDD and neurodegenerative diseases. In addition, there is evidence that psychological stress and MDD are associated with molecular and cellular signs of accelerated aging. This review will highlight the relationship between MDD, the aging process, and neurodegenerative diseases, emphasizing the neurochemical processes involved. PMID- 27370939 TI - Electroacupuncture analgesia with different frequencies is mediated via different opioid pathways in acute visceral hyperalgesia rats. AB - AIMS: To investigate the efficacy of electroacupuncture (EA) alleviation of acute visceral hyperalgesia, the frequency dependence of this efficacy, and the difference in endogenous opioid pathways as underlying mechanism explaining the frequency dependence. MAIN METHODS: A visceral hyperalgesia model was established by colorectal instillation of 2% acetic acid (AA) in adult rats. EA treatment at 2Hz, 100Hz, 2/100Hz and sham EA were performed at two bilateral acupoints, ST-36 and ST-37, in the hind-limbs. Naloxone (NLX, 2mg/kg) was administered intraperitoneally 5min before the application of EA. The visceral sensation was quantified by scores of abdominal withdrawal reflex (AWR) and values of rectus abdominis electromyograms (EMGs) in response to colorectal distension (CRD). KEY FINDINGS: Acute visceral hyperalgesia was produced by instillation of AA. The hyperalgesia reached the peak at 2h, and maintained steadily for >6h. EA treatment at 2Hz, 100Hz and 2/100Hz attenuated the acute hyperalgesia, and the attenuation lasted for 2.5h, 2h and 3h, respectively. Sham EA produced no such effect. The analgesic potencies of EA treatment at 2Hz, 100Hz and 2/100Hz were completely blocked, almost not affected, and partially blocked by NLX. In the latter two frequencies, the analgesic durations were shortened to 1.5h and 2h, respectively. SIGNIFICANCE: EA can alleviate acute visceral hyperalgesia. Effective EA analgesia at different frequencies are potentially mediated via different endogenous opioid pathways. PMID- 27370940 TI - The role of the Wnt canonical signaling in neurodegenerative diseases. AB - The Wnt/beta-catenin or Wnt canonical pathway controls multiple biological processes throughout development and adult life. Growing evidences have suggested that deregulation of the Wnt canonical pathway could be involved in the pathogenesis of neurodegenerative diseases. The Wnt canonical signaling is a pathway tightly regulated, which activation results in the inhibition of the Glycogen Synthase Kinase 3beta (GSK-3beta) function and in increased beta-catenin activity, that migrates into the nucleus, activating the transcription of the Wnt target genes. Conversely, when the Wnt canonical pathway is turned off, increased levels of GSK-3beta promote beta-catenin degradation. Hence, GSK-3beta could be considered as a key regulator of the Wnt canonical pathway. Of note, GSK-3beta has also been involved in the modulation of inflammation and apoptosis, determining the delicate balance between immune tolerance/inflammation and neuronal survival/neurodegeneration. In this review, we have summarized the current acknowledgements about the role of the Wnt canonical pathway in the pathogenesis of some neurodegenerative diseases including Alzheimer's disease, cerebral ischemia, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis, with particular regard to the main in vitro and in vivo studies in this field, by reviewing 85 research articles about. PMID- 27370942 TI - An approach for the development of emergency response levels for halogenated hydrocarbons. AB - Emergency exposure guidance levels have been developed for many halogenated hydrocarbons. These can be employed in the event of accidental releases or terrorist actions. However, for a chemical release involving a substance without existing guidance levels, there is a need to be able to develop one rapidly. Two data sources are available, the Acute Exposure Guideline Levels (AEGL) and Emergency Response Guideline Levels (ERPG). The subset of halogenated hydrocarbons and related substances included in these data sources represent 30 chemicals and 41 risk assessments. The ratios for serious toxicity/annoyance level and for potential lethality/serious toxicity were calculated. On reviewing the results, the geometric means provided the best basis for extrapolation. When the geometric means of the ratios of ERPG-3/ERPG-2 and AEGL-3/AEGL-2 were calculated their combined mean was 4.40. The geometric standard deviation for the combined data set was 2.00 suggesting the data were homogeneous. Likewise, calculation of the geometric means for ERPG-2/1 and AEGL-2/1 the combined ratio was 3.93. The geometric standard deviation for the combined set was 1.46, again suggesting homogeneity of the data. The review described in this paper confirmed that the time default "n" values of 3 and 1 (ten Berge et al., 1986) are appropriate for extrapolation to shorter and longer exposure times, respectively. PMID- 27370941 TI - Reduced anaesthetic requirements and postoperative analgesics in patients undergoing laparoscopic cholecystectomy: premedication with intravenous paracetamol versus ketorolac, a double blind and randomised clinical trial. AB - OBJECTIVE: To compare the effects of premedication with intravenous paracetamol versus ketorolac, in decreasing intraoperative anaesthetic and postoperative opioid analgesics requirements in patients undergoing laparoscopic cholecystectomy. METHOD: An experimental, prospective, comparative, double blind, and randomised clinical trial was conducted to determine intraoperative opioid requirements, and pain and analgesic requirements in the postoperative period in 100 healthy patients undergoing laparoscopic cholecystectomy. They were randomised into 2 groups: Group 1: pre-medicated with paracetamol 1g, and Group 2: with ketorolac 30mg (both administered intravenously 30minutes prior to surgery). RESULTS: There were no statistically significant differences between groups as regards intraoperative remifentanil use (Group 1: 0.0739+/ 0.016MUg/kg/min, Group 2: 0.0741+/-0.018MUg/kg/min). The number of patients in Group 2 that had values of VAS>4 points (22.4%) was lower than in Group 1 (28.6%), but with no statistically significant difference. Of the patients who needed postoperative opioid rescue, most required a single rescue and application of analgesics during hospitalisation, that prevailed between 3 and 12hours, without any significant differences between groups. No adverse effects were observed in the study sample. CONCLUSION: Paracetamol 1g IV given preoperatively decreased anaesthetic requirements and the need for postoperative analgesics similar to the preoperative administration of ketorolac 30mg IV. PMID- 27370943 TI - The Relationship Between Television Sports Exposure and Rape Myth Acceptance: The Mediating Role of Sexism and Sexual Objectification of Women. AB - Rape affects a large proportion of women in the United States but is one of the most underreported crimes. It is believed that rape myth acceptance contributes to low reporting rates. We tested whether television sports exposure was indirectly related to higher acceptance of rape myth beliefs. An online survey involving 465 undergraduate students showed that viewing TV sports was positively related to hostile sexism, benevolent sexism, and sexual objectification of women. Through these variables, TV sports was indirectly and positively associated with rape myth acceptance. These results suggest that sports programming contributes to the perpetuation of rape myths in society. PMID- 27370944 TI - Variability, frequency composition, and temporal regularity of submaximal isometric elbow flexion force in subacute stroke. AB - We compared variability, frequency composition, and temporal regularity of submaximal isometric elbow flexion force at 10, 20, 35, and 50 % of peak torque between 34 stroke subjects (5-48 days post-onset, both arms) and 24 age-matched controls (dominant arm), and related the findings in the paretic arm to motor impairment. Force variability was quantified by the coefficient of variation (CV), frequency composition by the median frequency and relative power in 0-3-, 4 6-, and 8-12-Hz bands, and regularity by the sample entropy (SampEn). The paretic elbow flexors showed significantly increased CV and relative power in 0-3-Hz band, decreased power in 4-6- and 8-12-Hz bands, and decreased SampEn compared to both the non-paretic and control elbow flexors (P <= 0.0002), with no differences between the latter two (P >= 0.012). With increasing contraction intensity, the relative power in different frequency bands was insufficiently modulated and SampEn excessively decreased in the paretic elbow flexors. Also, CV in the paretic elbow flexors was non-linearly related to the relative power in different frequency bands and SampEn across contraction intensities (rectangular hyperbolic fit, 0.21 <= R 2 <= 0.55, P <= 0.006), whereas no force parameter correlated with arm motor impairment. These results largely extend our previous findings in the paretic knee extensors to the elbow flexors in subacute stroke, except that here force variability was increased only in the paretic elbow flexors and modulation of force regularity with increasing contraction intensity showed the opposite, decreasing pattern, which was considerably exaggerated in the paretic muscles. PMID- 27370945 TI - Low back and neck and shoulder pain in members and non-members of adolescents' sports clubs: the Finnish Health Promoting Sports Club (FHPSC) study. AB - BACKGROUND: The objective of this study was to investigate the prevalence of self reported low back pain (LBP) and neck and shoulder pain (NSP), and the related factors in members and non-members of adolescents' sports clubs. METHODS: This cross-sectional study was based on surveys of 14-16-year-olds as a part of the Finnish Health Promoting Sports Club (FHPSC) Study. The surveys on self-reported health behaviours, injuries, and musculoskeletal health were conducted among sports club members (n = 962) and non-members (n = 675). Binary logistic regression analysis was applied to study the associations between dependent variables of LBP and NSP, and the independent factors. RESULTS: The prevalence of LBP during the preceding 3 months was 35.0 % in girls and 24.5 % in boys (p < 0.05 for sex difference). The prevalence of NSP was 55.9 % in girls and 27.3 % in boys (p < 0.001 for sex difference). Being a sports club member increased the odds for LBP in boys (odds ratio [OR] 2.35, 95 % CI 1.48-3.72). On the other hand, sports club participation was associated with lower odds of frequent NSP in girls (OR 0.52, 95 % CI 0.33-0.82). No associations were found between other leisure-time physical activity and LBP or NSP. Higher screen time (computer games, TV/DVD, phone, Internet) during leisure-time increased the odds of NSP in boys and LBP in boys and girls. CONCLUSIONS: In this study, self-reported LBP and NSP were already relatively common among adolescents. Girls have a higher risk for reporting LBP and NSP. Measures that are more effective in the prevention of LBP in male sports club members are needed. Excessive screen time is weakly associated with LBP and NSP, which should be taken into account in health promotion among adolescents. PMID- 27370947 TI - [Not Available]. PMID- 27370948 TI - [Not Available]. PMID- 27370946 TI - Flow diverter effect of LVIS stent on cerebral aneurysm hemodynamics: a comparison with Enterprise stents and the Pipeline device. AB - BACKGROUND: The aim of this study was to quantify the effect of the new Low profile Visualized Intraluminal Support (LVIS(r)D) device and the difference of fluid diverting effect compared with the Pipeline device and the Enterprise stent using computational fluid dynamics (CFD). METHODS: In this research, we simulated three aneurysms constructed from 3D digital subtraction angiography (DSA). The Enterprise, LVIS and the Pipeline device were virtually conformed to fit into the vessel lumen and placed across the aneurysm orifice. Computational fluid dynamics analysis was performed to compare the hemodynamic differences such as WSS, Velocity and Pressure among these stents. RESULTS: Control referred to the unstented model, the percentage of hemodynamic changes were all compared to Control. A single LVIS stent caused more wall shear stress reduction than double Enterprise stents (39.96 vs. 30.51 %) and velocity (23.13 vs. 18.64 %). Significant reduction in wall shear stress (63.88 %) and velocity (46.05 %) was observed in the double-LVIS stents. A single Pipeline showed less reduction in WSS (51.08 %) and velocity (37.87 %) compared with double-LVIS stent. The double Pipeline stents resulted in the most reduction in WSS (72.37 %) and velocity (54.26 %). Moreover, the pressure increased with minuscule extent after stenting, compared with the unstented model. CONCLUSIONS: This is the first study analyzing flow modifications associated with LVIS stents. We found that the LVIS stent has certain hemodynamic effects on cerebral aneurysms: a single LVIS stent caused more flow reductions than the double-Enterprise stent but less than a Pipeline device. Nevertheless, the double-LVIS stent resulted in a better flow diverting effect than a Pipeline device. PMID- 27370949 TI - [Not Available]. PMID- 27370952 TI - [Not Available]. PMID- 27370951 TI - [Not Available]. PMID- 27370950 TI - It's immoral, but I'd do it! Psychopathy traits affect decision-making in sacrificial dilemmas and in everyday moral situations. AB - This research investigated whether emotional hyporeactivity affects moral judgements and choices of action in sacrificial moral dilemmas and in everyday moral conflict situations in which harm to other's welfare is differentially involved. Twenty-six participants with high trait psychopathy (HP) and 25 with low trait psychopathy (LP) were selected based on the primary psychopathy scale of the Levenson Self-Report Psychopathy Scale. HP participants were more likely to sacrifice one person to save others in sacrificial dilemmas and to pursue a personal advantage in everyday moral situations entailing harm to another's good. While deciding in these situations, HP participants experienced lower unpleasantness as compared to LP participants. Conversely, no group differences emerged in choice of action and unpleasantness ratings for everyday moral situations that did not entail harm to others. Importantly, moral judgements did not differ in the two groups. These results suggest that high psychopathy trait affects choices of action in sacrificial dilemmas because of reduced emotional reactivity to harmful acts. The dissociation between choice of action and moral judgement suggests that the former is more closely related to emotional experience. Also, emotion seems to play a critical role in discriminating harmful from harmless acts and in driving decisions accordingly. PMID- 27370953 TI - [Not Available]. PMID- 27370954 TI - [Not Available]. PMID- 27370955 TI - [Not Available]. PMID- 27370956 TI - [Not Available]. PMID- 27370957 TI - [Not Available]. PMID- 27370958 TI - [Not Available]. PMID- 27370959 TI - [Not Available]. PMID- 27370961 TI - Mechanism of vasorelaxation induced by eupatorin in the rats aortic ring. AB - Previous studies demonstrated that eupatorin content in Orthosiphon stamineus fractions correlated with their vasorelaxation activity. Even with previous studies, there is still very little information on the vasorelaxation effect of eupatorin, and not many scientific studies had been carried out. Therefore, the present study was designed to investigate the vasorelaxation activity and mechanism of action of eupatorin. The vasorelaxation activity and the underlying mechanisms of eupatorin was evaluated on thoracic aortic rings isolated from Sprague Dawley rats. Eupatorin caused the relaxation of aortic rings pre contracted with phenylephrine with and without endothelium (pD2=6.66+/-0.13, EMAX=99.72+/-6.39%; pD2=6.10+/-0.22, EMAX=65.78+/-8.01%), and also the relaxation of endothelium-intact aortic rings pre-contracted with potassium chloride (pD2=6.20+/-0.30, EMAX=71.89+/-12.25%). In the presence of Nomega-nitro-l arginine methyl ester (pD2<4.60, EMAX=24.91+/-6.39%), methylene blue (pD2=6.05+/ 0.38, EMAX=66.79+/-9.69%), ODQ (pD25.84+/-0.32, EMAX=60.47+/-9.6%), indomethacin (pD2=6.27+/-0.21, EMAX=76.03+/-9.45%), tetraethylammonium (pD2=6.09+/-0.35, EMAX=69.35+/-11.31%), 4-aminopyridine (pD2=6.34+/-0.12, EMAX=76+/-6.1%), barium chloride (pD2=6.47+/-0.14, EMAX=79.61+/-10.02%), atropine (pD2=6.36+/-0.29, EMAX=86.47+/-12.95%) and propranolol (pD2=6.49+/-0.26, EMAX=83.2+/-12.01%), relaxation stimulated by eupatorin was significantly reduced. Eupatorin was also found to be active in reducing Ca(2+) release from sarcoplasmic reticulum and in blocking calcium channels. The present study demonstrates the vasorelaxation effect of eupatorin involving NO/sGC/cGMP and indomethacin pathways, calcium and potassium channels, and muscarinic and beta-adrenergic receptors. PMID- 27370960 TI - Steroid receptor coactivator-3 is a pivotal target of gambogic acid in B-cell Non Hodgkin lymphoma and an inducer of histone H3 deacetylation. AB - Gambogic acid (GA), the active ingredient from gamboges, has been verified as a potent anti-tumor agent in many cancer cells. Nevertheless, its function in lymphoma, especially in B-cell Non-Hodgkin lymphoma (NHL), remains unclear. Amplification and/or overexpression of steroid receptor coactivator-3 (SRC-3) have been detected in multiple tumors and have confirmed its critical roles in carcinogenesis, progression, metastasis and therapy resistance in these cancers. However, no clinical data have revealed the overexpression of SRC-3 and its role in B-cell NHL. In this study, we demonstrated the anti-tumor effects of GA, which included cell growth inhibition, G1/S phase cell cycle arrest and apoptosis in B cell NHL. We also verified that SRC-3 was overexpressed in B-cell NHL in both cell lines and lymph node samples from patients. The overexpressed SRC-3 was a central drug target of GA, and its down-regulation subsequently modulated down stream gene expression, ultimately contributing to apoptosis. Silencing SRC-3 decreased the expression of Bcl-2, Bcl-6 and cyclin D3, but not of NF-kappaB and IkappaB-alpha. GA treatment did not inhibit the activation of AKT signaling pathway, but induced the deacetylation of histone H3 at lysine 9 and lysine 27. Down-regulated SRC-3 was observed to interact with more HDAC1 to mediate the deacetylation of H3. As the component of E3 ligase, Cullin3 was up-regulated and mediated the degradation of SRC-3. Our results demonstrate that GA is a potent anti-tumor agent that can be used for therapy against B-cell NHL, especially against those with an abundance of SRC-3. PMID- 27370962 TI - Molecular mechanisms of cryptorchidism development: update of the database, disease comorbidity, and initiative for standardization of reporting in scientific literature. AB - Cryptorchidism is a frequent urogenital abnormality that may be present at birth (congenital form) or develop later in life (acquired form). It represents 2-4% full-term male births. It has a potential effect on health; defects in testes descent usually cause impaired spermatogenesis resulting in reduced fertility and increased rates of testicular neoplasia, and testicular torsion. In our previous study, we developed a cryptorchidism gene database which consists of 217 genomic variations associated with development of cryptorchidism in seven mammalian species. The number of studies and study approaches in this field are increasing; therefore, update of the database was needed. The search of multi-omics data was performed and the updated database includes 280 genomic variations associated with cryptorchidism in seven species. The catalog has been complemented with additional data including: number of participants (patients/controls), race/ethnicity, clinical data (age period at diagnosis), congenital/acquired cryptorchidism, unilateral (left/right)/bilateral cryptorchidism, disease comorbidity, and disease ontology. Collected data revealed that cryptorchidism has been reported to be co-present with 150 comorbid conditions, including several syndromes, reproductive, cardiovascular, ophthalmologic, dermatologic, mental, and bone disorders, deafness, and cancer. However, updating the database is time-consuming because of the heterogeneity of results and methodology in scientific literature. The field lacks a standardized format for reporting associations between genotype and phenotype which would enable faster development of the database, data integration, sharing, and facilitate biomarker development. Therefore, in this study, we updated a database of cryptorchidism genes and suggested a first step toward standardization of the format for reporting results of original as well as review studies which we suggest implementing into the scientific literature that reports genotype-cryptorchidism associations. PMID- 27370964 TI - Granulomatosis with polyangiitis mimicking infective endocarditis in an adolescent male. AB - Granulomatosis with polyangiitis (GPA) is a rare but serious small vessel vasculitis with heterogeneous clinical presentation ranging from mainly localised disease with a chronic course, to a florid, acute small vessel vasculitic form characterised by severe pulmonary haemorrhage and/or rapidly progressive vasculitis or other severe systemic vasculitic manifestations. Cardiac involvement is, however, uncommon in the paediatric population. We report a case of a 16-year-old male who presented with peripheral gangrene and vegetation with unusual location on the supporting apparatus of the tricuspid valve, initially considered to have infective endocarditis but ultimately diagnosed with GPA. We provide an overview of the limited literature relating to cardiac involvement in GPA, and the diagnostic challenge relating to infective endocarditis in this context, especially focusing on the interpretation of the antineutrophil cytoplasmic antibody (ANCA) and the characteristic clinical features to identify in order to promptly recognise GPA, since timely diagnosis and treatment are essential for this potentially life-threatening condition. PMID- 27370965 TI - [Not Available]. PMID- 27370966 TI - [Not Available]. PMID- 27370963 TI - Proinflammatory proteins in female and male patients with primary antiphospholipid syndrome: preliminary data. AB - The latest classification criteria for the diagnosis of the antiphospholipid syndrome (APS, an autoimmune disease characterized by thromboses, miscarriages and presence of antiphospholipid antibodies (Abs)) emphasized that thrombotic manifestations of APS should be without any signs of an inflammatory process. However, atherosclerosis (a chronic inflammatory response to the accumulation of lipoproteins in the walls of arteries) and APS are characterized by some similar features. We evaluated whether proinflammatory proteins were associated with the features of the primary APS (PAPS). PAPS patients without obstetric complications and with impaired lipid profile were included in the study. Antiphospholipid antibodies, TNF-alpha, and apo(a) were determined by ELISA. Complement components and hsCRP were measured by immunonephelometry. Decreased C3c was observed in female patients with increased titers of IgG anti-beta2gpI (chi(2) = 3.939, P = 0.047) and in male patients with increased IgM anticardiolipin Abs (chi(2) = 4.286, P = 0.038). Pulmonary emboli were associated with interleukin (IL)-6 in male (chi(2) = 6.519, P = 0.011) and in female (chi(2) = 10.405, P = 0.001) patients. Cerebrovascular insults were associated with LDL-cholesterol (P = 0.05, 95 % CI: 1.003 - 12.739) in female and with apo(a) (P = 0.016, 95 % CI: 0.000 0.003) in male patients. Older female patients had increased LDL-cholesterol levels and frequency of myocardial infarctions. Proinflammatory proteins were associated with features of primary APS. No real gender differences in regard to proinflammatory protein levels were observed. Premenopausal state of female PAPS patients confers lower cardiovascular risk. PMID- 27370967 TI - [Not Available]. PMID- 27370969 TI - [Not Available]. PMID- 27370968 TI - [Not Available]. PMID- 27370970 TI - [Not Available]. PMID- 27370971 TI - [Not Available]. PMID- 27370972 TI - [Not Available]. PMID- 27370973 TI - An oral chitosan DNA vaccine against nodavirus improves transcription of cell mediated cytotoxicity and interferon genes in the European sea bass juveniles gut and survival upon infection. AB - Vaccines for fish need to be improved for the aquaculture sector, with DNA vaccines and the oral administration route providing the most promising improvements. In this study, we have created an oral chitosan-encapsulated DNA vaccine (CP-pNNV) for the nodavirus (NNV) in order to protect the very susceptible European sea bass (Dicentrarchus labrax). Our data show that the oral CP-pNNV vaccine failed to induce serum circulating or neutralizing specific antibodies (immunoglobulin M) or to up-regulate their gene expression in the posterior gut. However, the vaccine up-regulated the expression of genes related to the cell-mediated cytotoxicity (CMC; tcrb and cd8a) and the interferon pathway (IFN; ifn, mx and ifng). In addition, 3 months after vaccination, challenged fish showed a retarded onset of fish death and lower cumulative mortality with a relative survival of 45%. Thus, we created a chitosan-encapsulated DNA vaccine against NNV that is partly protective to European sea bass juveniles and up regulates the transcription of genes related to CMC and IFN. However, further studies are needed to improve the anti-NNV vaccine and to understand its mechanisms. PMID- 27370974 TI - Identification and functional analysis of the toll-like receptor 20.2 gene in grass carp, Ctenopharyngodon idella. AB - We characterized and identified the cDNA sequence of Toll-like receptor 20.2 in Ctenopharyngodon idella (gctlr20.2); it consisted of 3197 bp, with an open reading frame of 2835 bp that encoded a 944 amino acid polypeptide. Relatively, high expression levels of gctlr20.2 were observed in the spleen, head kidney, liver and brain tissues, with lower expression levels in the trunk kidney, intestine and heart tissues. In vivo and in vitro, after being challenged with Aeromonas hydrophila or grass carp reovirus (GCRV), gctlr20.2 expression was induced in C. idella kidney cells stimulated with lipopolysaccharide, flagellin or polyinosinic-polycytidylic acid. Overexpression of gctlr20.2 increased the expression of il1beta, il8 and tnf-alpha, but not ifn, and also increased the activity of the nf-kappaB signal pathway. Silencing, via siRNA-tlr20.2, inhibited gctlr20.2 transcription by 65.7% and down-regulated the expression of inflammatory cytokine genes, but not tnf-alpha. This study increases understanding of the immune system in C. idella. PMID- 27370976 TI - M-Health for Improving Screening Accuracy of Acute Malnutrition in a Community Based Management of Acute Malnutrition Program in Mumbai Informal Settlements. AB - BACKGROUND: Acute malnutrition is linked to child mortality and morbidity. Community-Based Management of Acute Malnutrition (CMAM) programs can be instrumental in large-scale detection and treatment of undernutrition. The World Health Organization (WHO) 2006 weight-for-height/length tables are diagnostic tools available to screen for acute malnutrition. Frontline workers (FWs) in a CMAM program in Dharavi, Mumbai, were using CommCare, a mobile application, for monitoring and case management of children in combination with the paper-based WHO simplified tables. A strategy was undertaken to digitize the WHO tables into the CommCare application. OBJECTIVE: To measure differences in diagnostic accuracy in community-based screening for acute malnutrition, by FWs, using a mobile-based solution. METHODS: Twenty-seven FWs initially used the paper-based tables and then switched to an updated mobile application that included a nutritional grade calculator. Human error rates specifically associated with grade classification were calculated by comparison of the grade assigned by the FW to the grade each child should have received based on the same WHO tables. Cohen kappa coefficient, sensitivity and specificity rates were also calculated and compared for paper-based grade assignments and calculator grade assignments. RESULTS: Comparing FWs (N = 14) who completed at least 40 screenings without and 40 with the calculator, the error rates were 5.5% and 0.7%, respectively (p < .0001). Interrater reliability (kappa) increased to an almost perfect level (>.90), from .79 to .97, after switching to the mobile calculator. Sensitivity and specificity also improved significantly. CONCLUSION: The mobile calculator significantly reduces an important component of human error in using the WHO tables to assess acute malnutrition at the community level. PMID- 27370975 TI - Indoleamine 2,3-dioxygenase: First evidence of expression in rainbow trout (Oncorhynchus mykiss). AB - The role of enzymes as active antimicrobial agents of the innate immunity in teleost fish is proposed in diverse works. Secretion of Indoleamine 2,3 dioxygenase (IDO) has been described in higher vertebrates; it degrades l tryptophan in extracellular environments associated mainly with mucosal organs. The effect of IDO on decreasing amino acid concentration may inhibit the growth of potential pathogens. In fish the study of this molecule is still. Here we report the identification of an Onchorhyncus mykiss IDO homologue (OmIDO). IDO was cloned, sequenced, and the primary structure shows conservation of key functional sites. The constitutive expression is altered when the fish is challenged with LPS as a pathogen-associated molecular pattern (PAMPs). Up regulation of IDO was shown preferentially in the fish's mucosal cells. In order to obtain evidence of a possible regulation mechanism, an in vitro cell model was used for to show that OmIDO is induced by rIFN. These study has identified a Indoleamine 2,3-dyoxigenase in O. mykiss will contribute to expands our knowledge of the function this protein in fish immune response. These findings allow to propose the use of OmIDO as a molecular indicator of strength of the animal's immune response and wellbeing. PMID- 27370977 TI - Dietary B Vitamins and Serum C-Reactive Protein in Persons With Human Immunodeficiency Virus Infection: The Positive Living With HIV (POLH) Study. AB - BACKGROUND: B vitamins may have beneficial roles in reducing inflammation; however, research on the role of B vitamins in inflammation among HIV-infected persons is lacking. OBJECTIVE: This study assessed the association between B vitamins and serum C-reactive protein (CRP) concentrations in HIV-infected persons. METHODS: A cross-sectional survey was conducted among 314 HIV-infected persons (180 men and 134 women) aged 18 to 60 years residing in the Kathmandu, Nepal. High-sensitive and regular serum CRP concentrations were measured by the latex agglutination nephelometry and latex agglutination turbidimetric method, respectively. Dietary intake was assessed using 2 nonconsecutive 24-hour dietary recalls. The relationships between B vitamins and serum CRP concentrations were assessed using multiple regression analysis. RESULTS: The multivariate-adjusted geometric mean of serum CRP concentrations was significantly decreased with an increasing B vitamins intake across quartiles of niacin (P for trend = .007), pyridoxine (P for trend = .042), and cobalamin (P for trend = .037) in men. In men, the mean serum CRP concentrations in the highest quartiles of niacin, pyridoxine, and cobalamin were 63%, 38%, and 58%, respectively, lower than that in the lowest quartile. In women, the mean serum CRP concentrations in the highest quartiles of riboflavin (P for trend = .084) and pyridoxine (P for trend = .093) were 37% and 47%, respectively, lower than that in the lowest quartile. CONCLUSION: High intake of niacin, pyridoxine, or cobalamin was independently associated with decreased serum CRP concentrations among HIV-infected men. Further prospective studies are warranted to confirm the role of B vitamins in inflammation among HIV-infected persons. PMID- 27370978 TI - [Not Available]. PMID- 27370979 TI - [Not Available]. PMID- 27370981 TI - [Not Available]. PMID- 27370980 TI - [Not Available]. PMID- 27370982 TI - [Not Available]. PMID- 27370983 TI - [Not Available]. PMID- 27370984 TI - [Not Available]. PMID- 27370985 TI - [Not Available]. PMID- 27370986 TI - [Not Available]. PMID- 27370987 TI - [Not Available]. PMID- 27370988 TI - [Not Available]. PMID- 27370990 TI - [Not Available]. PMID- 27370991 TI - Pattern of chronic myeloid leukemia in the imatinib era in a Sub-Saharan African setting. AB - Chronic myeloid leukemia (CML) is an orphan disease in Africa because of the inaccessibility to specific treatment and the high cost of diagnosis and monitoring patients. The aim of this study was to report CML treatment response in a developing country in the tyrosine kinase inhibitor era. We conducted a longitudinal study of our cohort of CML patients. Socio-demographic, diagnosis, therapeutic, and treatment response parameters were studied. Sokal score, disease phase at diagnosis, delay from diagnosis to treatment, and treatment response were analyzed for their impact on survival. Fifty-five patients with a diagnosis of CML and who received treatment with imatinib for a minimum of 3 months were included in this study. Median follow-up was 170 patient-years. The sex ratio (M/F) was 1.62 and median age at diagnosis was 42 years. At diagnosis, 85.5 % of the patients were in chronic phase (CP), 12.7 % in accelerated phase (AP), and 1.8 % in blast crisis (BC). Sokal risk score distribution was as follows: low risk 29.8 %, intermediate risk 38.3 %, and high risk 31.9 %. Median time from first symptoms to first medical visit was 6.2 months and median time from first medical visit to cytogenetic and or molecular confirmation was 12.4 months. Mean delay time from first medical visit to imatinib initiation was 12.5 months (95 % CI 6.3-18.7). The complete hematologic response (CHR) at 3 months, the major cytogenetic response (MCR) at 12 months, and the major molecular response (MMR) at 24 months were respectively 82.4, 75, and 25 %. The 2-year overall survival rate was 81 %. Advanced phase at the diagnosis, discontinuation of imatinib therapy over 15 % of the time, lack of CHR at 3 months, lack of MCR at 12 months, and progression of the disease during imatinib therapy were associated with a risk of death (p <= 0.05). Our data confirm the improved prognosis of CML treated with imatinib in the setting of a developing country. However, response rates are lower than in developed countries, and additional efforts should be made to facilitate early diagnosis and improve access to TKI, treatment compliance, and regular molecular monitoring of patients. PMID- 27370992 TI - Long-term outcome following splenectomy for chronic and persistent immune thrombocytopenia (ITP) in adults and children : Splenectomy in ITP. AB - The purpose of this research is to study the outcomes of splenectomy for chronic and persistent immune thrombocytopenia (ITP). This study is a retrospective analysis of 254 patients with chronic or persistent ITP who underwent splenectomy at CMC, Vellore, India between 1995 and 2009. Responses were assessed based on standard criteria. One hundred and sixty seven adults and 87 children with a median age of 29 years (range 2-64) with persistent (n = 103) or chronic ITP (n = 151) was studied. Response was seen in 229 (90.2 %) including CR in 74.4 % at a median time of 1 day (range 1-54). Infections following splenectomy were reported in 16 %. Deaths related to post splenectomy sepsis occurred in 1.57 % and major bleeding in 0.78 %. At median follow-up of 54.3 months (range 1-290), 178 (70.1 %) remain in remission. The 5-year and 10-year overall survival (OS) is 97.4 +/- 1.2 % and 94.9 +/- 2.1 %, respectively, while the 5-year and 10-year event-free survival (EFS) is 76.5 + 2.9 % and 71.0 + 3.9 %, respectively. Splenectomy is associated with long-term remission rates of >70 % in chronic or persistent ITP. PMID- 27370993 TI - Central nervous system relapse in patients with diffuse large B cell lymphoma: analysis of the risk factors and proposal of a new prognostic model. AB - Central nervous system (CNS) relapse in patients with diffuse large B cell lymphoma (DLBCL) is an uncommon event, and the outcome of patients with CNS relapse is poor. However, no reliable prediction models for CNS relapse have been developed. We retrospectively analyzed consecutive de novo DLBCL patients referred to our department between September 2004 and August 2015 and treated with R-CHOP or R-CHOP-like regimens. Of 413 patients analyzed in this study, a total of 27 patients (6.5 %) eventually developed CNS relapse. The 5-year probability of CNS relapse was 8.4 %. The median time from diagnosis of DLBCL to CNS relapse was 15 months, and the median survival after CNS relapse was 7 months. In univariate analysis, the risk factors significantly associated with CNS relapse were Ann Arbor stage 3 or 4, albumin level <3.2 mg/L, number of extranodal sites >1, and involvement of retroperitoneal lymph node. We developed a new prognostic model consisting of these four factors. The 5-year probability of CNS relapse was significantly higher in patients with at least three of these four factors than in those with two or fewer factors (26.4 vs. 3.0 %, P < 0.001). Using this model, we evaluated the incidence and the risk factors of CNS relapse in DLBCL patients. The new risk model consisting of the four factors demonstrated good risk stratification for CNS relapse, and could help to identify high-risk patients for whom CNS prophylaxis is warranted. PMID- 27370994 TI - Biaxial flexural strength of new Bis-GMA/TEGDMA based composites with different fillers for dental applications. AB - OBJECTIVE: The aim of this study was to evaluate whether the mechanical properties of the modern dental composites can be improved by using tetrapodal ZnO particles as fillers in a Bis-GMA/TEGDMA matrix. Another aim was to test whether the mechanical properties of the composite are influenced by functionalization of the ZnO particles with lauric acid to achieve antibacterial activity. METHODS: Different filler materials and particle shapes (spherical zirconia, spherical zinc oxide, tetrapodal zinc oxide) were used to produce Bis GMA/TEGDMA based composites with a filler content of 40wt.-% and 60wt.-%, respectively. In addition, functionalization with lauric acid was investigated. For the biaxial flexural strength testing 104 test disks (N=8) with a diameter of 15mm and a thickness of 1.5mm were produced. RESULTS: Functionalization with lauric acid resulted in a decrease in biaxial flexural strength for all filler materials. The biaxial flexural strength decreased when using a higher filler content with spherical particles but increased when using tetrapodal zinc oxide particles. SIGNIFICANCE: A higher durability of the composites using tetrapodal zinc oxide particles. An antibacterial functionalization with lauric acid cannot be recommended as the mechanical stability of the composite will be reduced. PMID- 27370996 TI - [Not Available]. PMID- 27370997 TI - [Not Available]. PMID- 27370995 TI - Polymerization stress of experimental composites containing random short glass fibers. AB - OBJECTIVE: To test the null hypotheses that (1) the replacement of particles by short fibers does not affect polymerization stress (PS), flexural modulus (FM) or volumetric shrinkage (VS) of experimental composites and (2) PS is not affected by specimen thickness. METHODS: Three experimental composites were prepared, each containing similar mass fractions of BisGMA and TEGDMA and 60 vol% of fillers, being 0%, 3% or 6% constituted by 1.6-mm long glass fibers and the remaining by 1MUm glass particles. PS (n=5) was tested in a high compliance system, using two specimen heights (1.5mm and 4.0mm). VS and maximum shrinkage rate were obtained in a mercury dilatometer (n=3). FM was tested in three-point bending (n=10). As an additional control, a commercial composite (Filtek Z250, 3M ESPE) was tested. Data were recorded 10min after the onset of photoactivation and analyzed by ANOVA/Tukey test (FM only) and Kruskal-Wallis (alpha: 5%). RESULTS: At both specimen heights, the composite with 3% of fibers presented significantly higher PS than the controls (which showed similar PS values). Replacing 6% of particles by fibers did not increase PS significantly. FM was reduced in the presence of fibers, and 6% of fibers led to a decrease in VS. Shrinkage rate was not affected by the fibers. SIGNIFICANCE: Replacing 3vol% of particles by fibers resulted in significantly higher PS, which was associated to a decrease in FM compared to the control. PS was not affected by specimen height for any of the tested materials. PMID- 27370998 TI - [Not Available]. PMID- 27370999 TI - [Not Available]. PMID- 27371001 TI - [Not Available]. PMID- 27371000 TI - [Not Available]. PMID- 27371002 TI - [Not Available]. PMID- 27371003 TI - [Not Available]. PMID- 27371004 TI - [Not Available]. PMID- 27371005 TI - [Not Available]. PMID- 27371006 TI - [Not Available]. PMID- 27371007 TI - [Not Available]. PMID- 27371008 TI - [Not Available]. PMID- 27371009 TI - [Not Available]. PMID- 27371011 TI - [Not Available]. PMID- 27371010 TI - [Not Available]. PMID- 27371012 TI - [Not Available]. PMID- 27371013 TI - [Not Available]. PMID- 27371015 TI - [Not Available]. PMID- 27371014 TI - [Not Available]. PMID- 27371016 TI - Comparison of gas chromatography-combustion-mass spectrometry and gas chromatography-flame ionization detector for the determination of fatty acid methyl esters in biodiesel without specific standards. AB - GC-FID has been effectively used as a universal quantification technique for volatile organic compounds for a long time. In most cases, the use of the ECN allows for quantification by GC-FID without external calibration using only the response of a single internal standard. In this paper we compare the performance characteristics of GC-FID with those of post-column (13)C Isotope Dilution GC Combustion-MS for the absolute quantification of organic compounds without the need for individual standards. For this comparison we have selected the quantification of FAMEs in biodiesel. The selection of the right internal standard was critical for GC-FID even when ECN were considered. On the other hand, the nature of the internal standard was not relevant when GC-Combustion-MS was employed. The proposed method was validated with the analysis of the certified reference material SRM 2772 and comparative data was obtained on real biodiesel samples. The analysis of the SRM 2772 biodiesel provided recoveries in the range 100.6-103.5% and 96.4-103.6% for GC-combustion-MS and GC-FID, respectively. The detection limit for GC-combustion-MS was found to be 4.2ng compound/g of injected sample. In conclusion, the quantitative performance of GC Combustion-MS compared satisfactorily with that of GC-FID constituting a viable alternative for the quantification of organic compounds without the need for individual standards. PMID- 27371017 TI - Microchip electrophoresis with background electrolyte containing polyacrylic acid and high content organic solvent in cyclic olefin copolymer microchips for easily adsorbed dyes. AB - Plastic microchips can significantly reduce the fabrication cost but the adsorption of some analytes limits their application. In this work, background electrolyte containing ionic polymer and high content of organic solvent was adopted to eliminate the analyte adsorption and achieve highly efficient separation in microchip electrophoresis. Two dyes, rhodamine 6G (Rh6G) and rhodamine B (RhB) were used as the model analytes. By using methanol as the organic solvent and polyacrylic acid (PAA) as a multifunctional additive, successful separation of the two dyes within 75MUm id. microchannels was realized. The role of PAA is multiple, including viscosity regulator, selectivity modifier and active additive for counteracting analyte adsorption on the microchannel surface. The number of theoretical plate of 7.0*10(5)/m was attained within an effective separation distance of 2cm using background electrolyte consisting 80% methanol, 0.36% PAA and 30mmol/L phosphate at pH 5.0. Under optimized conditions, relative standard deviations of Rh6G and RhB detection (n=5) were no more than 1.5% for migration time and 2.0% for peak area, respectively. The limit of detection (S/N=3) was 0.1nmol/L for Rh6G. The proposed technique was applied in the determination of both Rh6G and RhB in chilli powder and lipstick samples with satisfactory recoveries of 81.3-103.7%. PMID- 27371018 TI - Ultrasonic-microwave method in preparation of polypyrrole-coated magnetic particles for vitamin D extraction in milk. AB - In this study, a nanocomposite of polypyrrole-coated magnetite nanoparticles (Fe3O4@PPy) was prepared by ultrasonic-microwave technique, and employed as magnetic solid-phase extraction (MSPE) sorbent for extraction of vitamin D from milk samples. The term of the synthesis by ultrasonic-microwave technique was dramatically shortened within 4h compared to 20h by conventional stirring-heating method. The resultant composites incorporating the pi-pi bonding (between PPy coating and the analytes) and magnetic separation can be applied for vitamin D analysis in complicated samples. Without saponification or protein precipitation, vitamin D2 and vitamin D3 could be captured directly from milk samples by Fe3O4@PPy, and separated by magnetic field with only 0.5mL desorption solvent. The total preparation time was completed within 15min. A method for the determination of vitamin D in milk samples by the Fe3O4@PPy extraction coupled with high performance liquid chromatography (HPLC) was developed. The LODs of vitamin D2 and vitamin D3, based on signal-to-noise ratio (S/N) of 3, were 0.02ng/mL and 0.05ng/mL respectively. The recoveries of vitamin D2 and vitamin D3 from milk samples were in the range of 71.9-90.3%, with relative standard deviations ranging between 3.6%-9.9%. The results indicated that the Fe3O4@PPy can be favorably used for the extraction of the vitamin D in milk samples. PMID- 27371019 TI - Two-step cleanup procedure for the identification of carotenoid esters by liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry. AB - Carotenoids are naturally found in both free form and esterified with fatty acids in most fruits; however, up to now the great majority of studies only evaluated their composition after saponification. This fact is easily explained by the difficult to analyze carotenoid esters. Preliminary studies showed that cleanup procedures in the extract are necessary for further analysis by LC-MS/MS since triacylglycerols (TAGs) impair the MS detection. Considering these facts, we developed a new cleanup procedure to remove TAGs and other lipids from carotenoid fruit extracts. This procedure is based on physical removal of solid lipids at low temperature followed by open column chromatography on MgO and diatomaceous earth. Before cleanup, four carotenoid diesters and two free xanthophylls were identified in murici (Byrsonyma crassifolia), corresponding to about 65% of the total chromatogram area. After carrying out the two-step cleanup procedure, 35 carotenoids were identified, being 14 monoesters, six free carotenoids and 15 carotenoid diesters. We can conclude that this two-step procedure was successfully applied to murici, an Amazonian fruit, which contains high amounts of lipids. PMID- 27371020 TI - Graphene oxide based sol-gel stainless steel fiber for the headspace solid-phase microextraction of organophosphate ester flame retardants in water samples. AB - In this paper, graphene oxide was coated onto a stainless steel wire through sol gel technique and it was used as a solid phase microextraction (SPME) fiber. The prepared fiber was characterized by scanning electron microscopy (SEM), which displayed that the fiber had crinkled surface and porous structure The application of the fiber was evaluated through the headspace SPME of nine organophosphate ester flame retardants (OPFRs) with different characteristics in water samples followed by gas chromatography and nitrogen-phosphorous detector (GC/NPD). The major factors influencing the extraction efficiency, including the extraction and desorption conditions, were studied and optimized. Under the optimum conditions, the proposed method was evaluated, and applied to the analysis of organophosphate ester flame retardants in real environmental water samples. The results demonstrated the HS-SPME method based on GO sol-gel fiber had good linearity (R>0.9928), and limits of detection (1.4-135.6ngL(-1)), high repeatability (RSD<9.8%) and good recovery (76.4-112.4%). The GO based sol-gel fiber displayed bigger extraction capability than the commercial PDMS fiber and the pure sol-gel fiber for both polar and apolar organophosphate esters, especially for the OPFRs containing benzene rings. PMID- 27371021 TI - Highly efficient solid-phase derivatization of sugar phosphates with titanium immobilized hydrophilic polydopamine-coated silica. AB - Sugar phosphates are a type of key metabolic intermediates of glycolysis, gluconeogenesis and pentose phosphate pathway, which can regulate tumor energetic metabolism. Due to their low endogenous concentrations, poor chromatographic retention properties as well as ionization suppression from complex matrix interference, the determination of sugar phosphates in biological samples is very difficult. In this study, titanium-immobilized hydrophilic polydopamine-coated silica microspheres (SiO2@PD-Ti(4+)) were synthesized for highly efficient solid phase derivatization of sugar phosphates. Sugar phosphates were selectively captured onto the surface of the SiO2@PD-Ti(4+) microspheres by chelating with phosphate groups, and then reacted with 3-amino-9-ethylcarbazole via reductive amination based on solid-phase derivatization, which could not only increase the retention and resolution of sugar phosphates on reversed-phase liquid chromatography (RPLC), but also improve the mass spectrometry (MS) sensitivity of sugar phosphates. The adsorption capacity of SiO2@PD-Ti(4+) microspheres towards glucose-6-phosphate is 0.76mg/g, which is much larger than that of commercial TiO2. Compared with the traditional liquid-phase derivatization, the solid-phase derivatization based on the SiO2@PD-Ti(4+) microspheres displayed several superiorities including shorter derivatization time (within 10min), higher product purity and much lower limit of detection (up to 38pmol/L). In addition, good linearity (R(2)>=0.99), excellent recovery (80.6-118%) and high precision (RSDs with 2.8-7.8%) were obtained when the developed method was used for quantitative analysis of sugar phosphates. Finally, the SiO2@PD-Ti(4+) microspheres combined with RPLC-MS were successfully applied to the determination of sugar phosphates from hepatocarcinoma cell lines and could even detect the trace sugar phosphates in thousands of cells. PMID- 27371022 TI - A facile and fully automated on-fiber derivatization protocol for direct analysis of short-chain aliphatic amines using a matrix compatible solid-phase microextraction coating. AB - Solid-phase microextraction (SPME) analysis of short-chain aliphatic amines (C3 C6) in aqueous solutions was investigated using pentafluorobenzaldehyde (PFBAY) as on-fiber derivatization reagent. A standard gas generating vial agent was used for on-fiber loading of the derivatization agent so as to avoid the need for its regeneration at each derivatization cycle. Several parameters such as loading time, reaction temperature, and reaction/extraction time were optimized for headspace and direct sampling in aqueous solutions. Three different coating chemistries were tested and their performances compared in order to achieve the best compromise between sensitivity and analysis throughput. The newly developed PDMS/DVB/PDMS coating showed superior performance in terms of extraction efficiency while the capability to prevent on-fiber degradation of the derivatizing products. The optimized method was used for quantitation of short chain aliphatic amines in aqueous samples and provided detection limits in the low ppb range for all the amines tested with accuracy values between 79 and 120%. The method was applied towards the analysis of environmental water samples and the accuracy of the results was evaluated by different calibration approaches. PMID- 27371023 TI - Enantioseparation of the constituents involved in the phenylalanine-tyrosine metabolic pathway by capillary electrophoresis tandem mass spectrometry. AB - Catecholamines dopamine, norepinephrine, and epinephrine are well-known neurotransmitters playing different roles in the nervous and endocrine system. These compounds are biologically synthesized in the phenylalanine-tyrosine pathway which consists on the successive conversion of l-phenylalanine into l tyrosine, l-3,4-dihydroxyphenylalanine (L-DOPA), dopamine, norepinephrine, and epinephrine. This work describes the development of an enantioselective CE-ESI MS2 methodology enabling, for the first time, the simultaneous enantioseparation of all the constituents involved in the Phe-Tyr metabolic pathway, since all these compounds except dopamine are chiral. The developed method was based on the use of a dual CDs system formed by 180mM of methyl-beta-CD and 40mM of 2 hydroxypropyl-beta-CD dissolved in 2M formic acid (pH 1.2) and presented the advantage of avoiding the use of any time-consuming labelling procedure. LODs ranged from 40 to 150nM and the unequivocal identification of the compounds investigated was achieved through their MS2 spectra. The applicability of this methodology to the analysis of biological samples (rat plasma) was also demonstrated. PMID- 27371024 TI - Coupling of multi-walled carbon nanotubes/polydimethylsiloxane coated stir bar sorptive extraction with pulse glow discharge-ion mobility spectrometry for analysis of triazine herbicides in water and soil samples. AB - An analytical method based on stir bar sorptive extraction (SBSE) coupled with pulse glow discharge-ion mobility spectrometry (PGD-IMS) was developed for analysis of three triazine pesticide residues in water and soil samples. An injection port with sealing device and stir bars hold device were designed and constructed to directly position the SBSE fiber including the extracted samples into the heating device, making desorption and detection of analytes proceeded simultaneously. The extraction conditions such as SBSE solid phase material, extraction time, extraction temperature, pH value and salt concentration were optimized. Mixture of MWCNTs-COOH and PDMS were shown to be effective in enriching the triazines. The LODs and LOQs of three triazines were found to be 0.006-0.015MUgkg(-1) and 0.02-0.05MUgkg(-1), and the linear range was 0.05 10MUgL(-1) with determination coefficients from 0.9987 to 0.9993. The SBSE-PGD IMS method was environmentally friendly without organic solvent consumption in the entire experimental procedures, and it was demonstrated to be a commendable rapid analysis technique for analysis of triazine pesticide residues in environmental samples on site. The proposed method was applied for the analysis of real ground water, surface water and soil samples. PMID- 27371025 TI - Effects of two kinds of imidazolium-based ionic liquids on the characteristics of steroid-transformation Arthrobacter simplex. AB - BACKGROUND: Ionic liquids (ILs) are a promising alternative for organic solvents because these liquids exhibit unique properties and enhanced steroid 1 dehydrogenation biotransformation caused by Arthrobacter simplex CPCC 140451 (ASP). However, the effect of ILs on the whole cell itself remains poorly understood and must be further investigated. RESULTS: A comparative investigation was performed to determine the effect of imidazolium-based ILs, namely, hydrophobic [PrMIm]PF6, and hydrophilic [PrMIm]BF4, on the steroid conversion, activity, permeability, and material basis of ASP cells. Both ILs weakened permeability barriers, enhanced steroid transformation, whereas reduced the activity of cells. The influence of [PrMIm]PF6 on the steroid conversion, permeability and activity of cells is more serious than that of [PrMIm]BF4 Transmission electron microscopy micrographs directly showed wrinkles, gross creases, and several small pores in ILs-treated cells surface. The total lipid content of [PrMIm]BF4-treated cells reduced by 8.3 %, while that of [PrMIm]PF6 treated cells reduced twice more, among which the content of long-chain fatty acids was decreased, whereas the content of unsaturated fatty acids was increased. The protein profile of LC-MS/MS revealed that the reduced proteins of cells treated with the two ILs were mainly located in the cytoplasm and plasma membrane, 19.27 % of reduced proteins were located on the cell membrane for [PrMIm]PF6-pretreated cells, whereas only 12.8 % for [PrMIm]BF4-pretreated cells. It suggests that most reduced proteins functioned in energy production and conversion, material transport and metabolism, signal recognition and transmission, transcription, and translation and posttranslational modification. In particular, the identified differential proteins functioned in the pentose phosphate pathway, synthesis of purines and pyrimidines, and oxidative phosphorylation and fatty acid pathway. CONCLUSION: Treatment with ILs improved permeability at the molecular level and exerted significant positive effects on steroid conversion. This study provides a material basis and elucidates the mechanisms underlying cellular changes that enhanced conversion rate. PMID- 27371027 TI - Authors' Response. PMID- 27371026 TI - Sarcoptes scabiei: genomics to proteomics to biology. AB - BACKGROUND: The common scabies mite, Sarcoptes scabiei is a cosmopolitan parasite of humans and other mammals. An annotated genome of Sarcoptes scabiei var. canis has been deposited in the National Center for Biotechnology Information (NCBI) and VectorBase and a proteomic analysis of proteins in extracts of mite bodies and eggs from this strain has been reported. Here we mined the data to identify predicted proteins that are known to be involved in specific biological processes in other animals. RESULTS: We identified predicted proteins that are associated with immunomodulation of the host defense system, and biological processes of the mite including oxygen procurement and aerobic respiration, oxidative metabolism, sensory reception and locating a host, neuronal transmission, stressors (heat shock proteins), molting, movement, nutrient procurement and digestion, and excretion and water balance. We used these data to speculate that certain biological processes may occur in scabies mites. CONCLUSION: This analysis helps understand the biology of Sarcoptes scabiei var. canis and adds to the data already available in NCBI and VectorBase. PMID- 27371028 TI - Identification of species and genetic variation in Taenia isolates from human and swine of North India. AB - Taenia solium is the major cause of taeniasis and cysticercosis/neurocysticercosis (NCC) in the developing countries including India, but the existence of other Taenia species and genetic variation have not been studied in India. So, we studied the existence of different Taenia species, and sequence variation in Taenia isolates from human (proglottids and cysticerci) and swine (cysticerci) in North India. Amplification of cytochrome c oxidase subunit 1 gene (cox1) was done by polymerase chain reaction (PCR) followed by sequencing and phylogenetic analysis. We identified two species of Taenia i.e. T. solium and Taenia asiatica in our isolates. T. solium isolates showed similarity with Asian genotype and nucleotide variations from 0.25 to 1.01 %, whereas T. asiatica displayed nucleotide variations ranged from 0.25 to 0.5 %. These findings displayed the minimal genetic variations in North Indian isolates of T. solium and T. asiatica. PMID- 27371029 TI - Changes in nociceptin/orphanin FQ levels in rat brain regions after acute and chronic cannabinoid treatment in conjunction with the development of antinociceptive tolerance. AB - It has been indicated that acute and chronic morphine administrations enhance nociceptin/orphanin FQ (N/OFQ) levels in the brain, which might play role in the development of tolerance to the antinociceptive effect of morphine. Accordingly, N/OFQ receptor (NOP) antagonists have been shown to prevent the development of antinociceptive tolerance to morphine. Our aim is to observe whether cannabinoids, similarly to opioids, enhance N/OFQ levels in pain-related brain regions and whether antagonism of NOP receptors attenuates the development of tolerance to the antinociceptive effect of cannabinoids. Hot plate and Tail flick tests are used to assess the antinociceptive response in Sprague-Dawley rats. N/OFQ levels are measured in cortex, amygdala, hypothalamus, periaqueductal gray, nucleus raphe magnus and locus coeruleus of rat brains using Western blotting and immunohistochemistry. Within 9 days, animals became completely tolerant to the antinociceptive effect of the cannabinoid agonist WIN 55,212-2 (2, 4, 6 mg/kg, i.p.). Chronic administration of JTC-801, a NOP receptor antagonist, at a dose that exerted no effect on its own (1 mg/kg, i.p.), attenuated development of tolerance to the antinociceptive effect of WIN 55,212-2 (4 mg/kg, i.p.). Western blotting and immunohistochemistry results showed that N/OFQ levels significantly increased in amygdala, periaqueductal gray, nucleus raphe magnus and locus coeruleus of rat brains when WIN 55,212-2 was combined with JTC-801. We hypothesize that, similar to opioids, chronic cannabinoid + NOP antagonist administration may enhance N/OFQ levels and NOP receptor antagonism prevents development of tolerance to cannabinoid antinociception. PMID- 27371032 TI - National Survey of Convention Centers' Lactation Facilities. AB - BACKGROUND: There is little published about lactation accommodations in public spaces. OBJECTIVE: The objective of this study was to determine what lactation facilities, if any, convention centers in the United States are providing to accommodate breastfeeding moms. METHODS: A list of national convention centers was collected from meetings-conventions.com and recorded in an Excel spreadsheet, with the name of the center, total meeting square feet, number of meeting rooms, address, and telephone number. Each convention center was contacted by phone and administered the survey. Questions were asked as to what type of lactation accommodations were available, if any. RESULTS: A response rate of 78.7% (326 of 414 convention centers) was achieved. A mere 5.5% reported permanently designated lactation rooms, whereas 32% made temporary accommodations. While the phone survey was conducted, a wide variety of qualitative responses were provided by participants, demonstrating an overall lack of awareness of this as a public health issue. CONCLUSION: Return to work and breastfeeding in public are commonly reported barriers to breastfeeding. This survey clearly demonstrates a lack of accommodations in very public areas that are visited by women on a regular basis. Policy changes are necessary so all women can be supported in reaching their personal breastfeeding goals. PMID- 27371030 TI - Dysregulations of Synaptic Vesicle Trafficking in Schizophrenia. AB - Schizophrenia is a serious psychiatric illness which is experienced by about 1 % of individuals worldwide and has a debilitating impact on perception, cognition, and social function. Over the years, several models/hypotheses have been developed which link schizophrenia to dysregulations of the dopamine, glutamate, and serotonin receptor pathways. An important segment of these pathways that have been extensively studied for the pathophysiology of schizophrenia is the presynaptic neurotransmitter release mechanism. This set of molecular events is an evolutionarily well-conserved process that involves vesicle recruitment, docking, membrane fusion, and recycling, leading to efficient neurotransmitter delivery at the synapse. Accumulated evidence indicate dysregulation of this mechanism impacting postsynaptic signal transduction via different neurotransmitters in key brain regions implicated in schizophrenia. In recent years, after ground-breaking work that elucidated the operations of this mechanism, research efforts have focused on the alterations in the messenger RNA (mRNA) and protein expression of presynaptic neurotransmitter release molecules in schizophrenia and other neuropsychiatric conditions. In this review article, we present recent evidence from schizophrenia human postmortem studies that key proteins involved in the presynaptic release mechanism are dysregulated in the disorder. We also discuss the potential impact of dysfunctional presynaptic neurotransmitter release on the various neurotransmitter systems implicated in schizophrenia. PMID- 27371035 TI - [Not Available]. PMID- 27371033 TI - Single best answer question-writing tips for clinicians. AB - Assessment is essential for progression in medical careers. Thus, an important aspect of developing as a clinical teacher is the ability to produce high-quality assessments for junior colleagues. The single best answer (SBA) question format is becoming ubiquitous in the assessment of the application of knowledge in clinical medicine; writing this style of examination question can be a challenge. This concise guide highlights key SBA question-writing tips, aiming to help aspiring clinical teachers set high-quality knowledge assessments. PMID- 27371034 TI - Doctors getting biggest payments from drug companies don't declare them on new website. PMID- 27371036 TI - [Not Available]. PMID- 27371031 TI - Long-term survival in advanced non-squamous NSCLC patients treated with first line bevacizumab-based therapy. AB - BACKGROUND/AIM: First-line bevacizumab-based therapies have been shown to improve clinical outcomes in patients with non-squamous non-small-cell lung cancer (NSCLC). We aimed to descriptively analyse patients with non-squamous NSCLC who received a long-term period of maintenance bevacizumab. PATIENTS AND METHODS: This retrospective study included 104 patients who had already reached a progression-free survival (PFS) of at least 9 months. RESULTS: Median overall survival and PFS were 30.7 and 15.1 months, respectively. The overall response rate was 83 %. Weight loss <=5 %, ECOG PS = 0, or low number of metastatic sites seem to be predictive factors of good evolution. The incidence of bevacizumab related adverse events appeared to be similar as the previous studies. CONCLUSION: Our findings show that there is a long-term survivor group whom the administration of bevacizumab resulted in a relevant prolongation of response without new safety signals. Due to the population heterogeneity, it was not possible to identify the standardised predictive factors. PMID- 27371038 TI - [Not Available]. PMID- 27371037 TI - [Not Available]. PMID- 27371039 TI - [Not Available]. PMID- 27371041 TI - [Not Available]. PMID- 27371040 TI - [Not Available]. PMID- 27371042 TI - [Not Available]. PMID- 27371043 TI - [Not Available]. PMID- 27371045 TI - [Not Available]. PMID- 27371044 TI - [Not Available]. PMID- 27371046 TI - [Not Available]. PMID- 27371047 TI - [Not Available]. PMID- 27371048 TI - [Not Available]. PMID- 27371049 TI - [Not Available]. PMID- 27371050 TI - [Not Available]. PMID- 27371052 TI - [Not Available]. PMID- 27371051 TI - [Not Available]. PMID- 27371053 TI - [Not Available]. PMID- 27371055 TI - [Not Available]. PMID- 27371054 TI - [Not Available]. PMID- 27371056 TI - [Not Available]. PMID- 27371057 TI - [Not Available]. PMID- 27371059 TI - [Not Available]. PMID- 27371058 TI - [Not Available]. PMID- 27371060 TI - [Not Available]. PMID- 27371062 TI - [Not Available]. PMID- 27371061 TI - [Not Available]. PMID- 27371063 TI - [Not Available]. PMID- 27371064 TI - [Not Available]. PMID- 27371066 TI - [Not Available]. PMID- 27371065 TI - [Not Available]. PMID- 27371067 TI - [Not Available]. PMID- 27371068 TI - [Not Available]. PMID- 27371069 TI - [Not Available]. PMID- 27371071 TI - [Not Available]. PMID- 27371070 TI - [Not Available]. PMID- 27371072 TI - [Not Available]. PMID- 27371073 TI - [Not Available]. PMID- 27371075 TI - [Not Available]. PMID- 27371074 TI - [Not Available]. PMID- 27371076 TI - [Not Available]. PMID- 27371077 TI - [Not Available]. PMID- 27371078 TI - [Not Available]. PMID- 27371079 TI - [Not Available]. PMID- 27371080 TI - [Not Available]. PMID- 27371081 TI - [Not Available]. PMID- 27371082 TI - [Not Available]. PMID- 27371083 TI - [Not Available]. PMID- 27371084 TI - [Not Available]. PMID- 27371085 TI - [Not Available]. PMID- 27371086 TI - [Not Available]. PMID- 27371087 TI - [Not Available]. PMID- 27371088 TI - [Not Available]. PMID- 27371090 TI - [Not Available]. PMID- 27371089 TI - [Not Available]. PMID- 27371091 TI - [Not Available]. PMID- 27371092 TI - [Not Available]. PMID- 27371093 TI - [Not Available]. PMID- 27371095 TI - Concerns when serum retinol concentration is the primary biological indicator of vitamin A status in intervention studies. PMID- 27371094 TI - Enhanced therapeutic effect of an antiangiogenesis peptide on lung cancer in vivo combined with salmonella VNP20009 carrying a Sox2 shRNA construct. AB - BACKGROUND: HM-3 is a polypeptide inhibiting angiogenesis. Recent reports suggest that the antitumor effect of angiogenesis inhibitors administered alone might be limited. Cancer stem cells can survive the lack of oxygen and nutrients. To achieve better anti-tumor effect, HM-3 was administered in combination with the attenuated Salmonella typhimurium VNP20009 transformed with a shRNA construct against sex determining region Y-box 2 (Sox2). METHODS: Cell invasion assay and soft agar colony formation assay were used to assess the migration and growth capability of A549 cells once Sox2 was knocked down with the shRNA construct. The shRNA construct targeting Sox2 was transformed into VNP20009. After the mouse xenograft model of A549 was established, HM-3 was co-administered with VNP20009 carrying the shRNA construct. The growth of tumor was checked to compare the effectiveness of different therapies. Western blotting assay and immunohistochemistry staining of the tumor tissue were used to measure the levels of proteins associated with the apoptosis pathway. RESULTS: Sox2 was necessary for the migration and growth of A549 cells. The expression of Sox2 was down regulated in the tumor tissue of the combined treatment group of HM-3 with VNP20009 carrying the Sox2 shRNA construct. Together with the accumulation of salmonella in tumor and the inhibition of angiogenesis by HM-3, more tumor cells went through cell apoptosis with increased expression of Bax, cleaved Caspase 3 and decreased expression of Bcl2. CONCLUSIONS: The results suggest the combination of antiangiogenesis agent HM-3 with gene therapy targeting Sox2 delivered by salmonella as a promising strategy for the treatment of lung cancer. PMID- 27371096 TI - Reply to SA Tanumihardjo et al. PMID- 27371097 TI - Erratum for Hildebrand et al. Association between birth weight and objectively measured sedentary time is mediated by central adiposity: data in 10,793 youth from the International Children's Accelerometry Database. Am J Clin Nutr 2015;101:983-90. PMID- 27371099 TI - Muscarinic cholinergic receptors (MR3) in saliva of patients with oral lichen planus. AB - Oral lichen planus (OLP) is a relatively common, chronic, and inflammatory mucocutaneous disease. Xerostomia is also a common complaint of most OLP patients. Considering the significant role of M3 muscarinic receptors (M3R) in secretion of saliva, this study sought to compare the level of this receptor in saliva between OLP patients and healthy controls. Forty OLP patients and 40 healthy controls filled out two questionnaires regarding xerostomia to assess its degree of severity. Unstimulated and stimulated salivary samples were obtained of both groups and the stimulated and unstimulated salivary flow rates were calculated. Salivary level of M3 muscarinic receptors was measured using the ELISA kit. Data were analyzed and compared using unpaired student's t test. P < 0.05 was considered significant. Stimulated and unstimulated salivary flow rates and M3 muscarinic receptors levels were significantly lower but degree of xerostomia was significantly higher in OLP patients compared to healthy controls. Salivary M3 muscarinic receptor seems to be low in the patients with OLP and these patients suffer from xerostomia and reduced salivary flow rate. PMID- 27371100 TI - A qPCR assay that specifically quantifies Tricholoma matsutake biomass in natural soil. AB - Tricholoma matsutake is an ectomycorrhizal basidiomycete that produces prized, yet uncultivable, "matsutake" mushrooms along densely developed mycelia, called "shiro," in the rhizosphere of coniferous forests. Pinus densiflora is a major host of this fungus in Japan. Measuring T. matsutake biomass in soil allows us to determine the kinetics of fungal growth before and after fruiting, which is useful for analyzing the conditions of the shiro and its surrounding mycorrhizosphere, predicting fruiting timing, and managing forests to obtain better crop yields. Here, we document a novel method to quantify T. matsutake mycelia in soil by quantifying a single-copy DNA element that is uniquely conserved within T. matsutake but is absent from other fungal species, including close relatives and a wide range of ectomycorrhizal associates of P. densiflora. The targeted DNA region was amplified quantitatively in cultured mycelia that were mixed with other fungal species and soil, as well as in an in vitro co culture system with P. densiflora seedlings. Using this method, we quantified T. matsutake mycelia not only from shiro in natural environments but also from the surrounding soil in which T. matsutake mycelia could not be observed by visual examination or distinguished by other means. It was demonstrated that the core of the shiro and its underlying area in the B horizon are predominantly composed of fungal mycelia. The fungal mass in the A or A0 horizon was much lower, although many white mycelia were observed at the A horizon. Additionally, the rhizospheric fungal biomass peaked during the fruiting season. PMID- 27371101 TI - Correlations of non-alcoholic fatty liver disease and serum uric acid with subclinical atherosclerosis in obese Chinese adults. AB - BACKGROUND: Existing evidence about the associations of non-alcoholic fatty liver disease (NAFLD) and serum uric acid (SUA) with subclinical atherosclerosis is controversial. The aim of the present study was to examine the associations of NAFLD and SUA with subclinical atherosclerosis. METHODS: In the present cross sectional study, 1354 obese adults underwent hepatic ultrasonography and arteriosclerosis detection. Indices of subclinical atherosclerosis were brachial ankle pulse wave velocity (ba-PWV) and the ankle-brachial index (ABI). Linear regression using multivariable fractional polynomial (MFP) modeling was used to examine independent associations of NAFLD and SUA with a-PWV and ABI. RESULTS: Compared with controls, mean (+/- SD) ba-PWV was significantly higher in subjects with NAFLD (1534 +/- 292 vs 1433 +/- 259 cm/s; P < 0.001) and hyperuricemia (HUA; 1519 +/- 275 vs 1476 +/- 287 cm/s; P = 0.007). After adjustment for sociodemographic and lifestyle factors, NAFLD and SUA were both positively related to ba-PWV (beta = 0.120 and 0.064, respectively; P < 0.05 for both). With further adjustment for insulin resistance and components of metabolic syndrome (MetS), the positive correlations were no longer significant (beta = 0.017 and 0.006; P > 0.05 for both). In addition, NAFLD, but not SUA, was negatively correlated with ABI (beta = -0.073; P = 0.015). Using MFP modeling, the best fractional polynomial (FP) transformation model showed that non-linear transformations were appropriate for two variables in their relationship with ba PWV, namely age and fasting insulin as first-degree FP transformations (age3 and 1/insulin0.5 , respectively). CONCLUSIONS: Neither NAFLD nor SUA was related to ba-PWV with increases in insulin resistance and MetS, but NAFLD was independently and negatively correlated with ABI. PMID- 27371102 TI - Costs of introducing pneumococcal, rotavirus and a second dose of measles vaccine into the Zambian immunisation programme: Are expansions sustainable? AB - BACKGROUND: Introduction of new vaccines in low- and lower middle-income countries has accelerated since Gavi, the Vaccine Alliance was established in 2000. This study sought to (i) estimate the costs of introducing pneumococcal conjugate vaccine, rotavirus vaccine and a second dose of measles vaccine in Zambia; and (ii) assess affordability of the new vaccines in relation to Gavi's co-financing and eligibility policies. METHODS: Data on 'one-time' costs of cold storage expansions, training and social mobilisation were collected from the government and development partners. A detailed economic cost study of routine immunisation based on a representative sample of 51 health facilities provided information on labour and vaccine transport costs. Gavi co-financing payments and immunisation programme costs were projected until 2022 when Zambia is expected to transition from Gavi support. The ability of Zambia to self-finance both new and traditional vaccines was assessed by comparing these with projected government health expenditures. RESULTS: 'One-time' costs of introducing the three vaccines amounted to US$ 0.28 per capita. The new vaccines increased annual immunisation programme costs by 38%, resulting in economic cost per fully immunised child of US$ 102. Co-financing payments on average increased by 10% during 2008-2017, but must increase 49% annually between 2017 and 2022. In 2014, the government spent approximately 6% of its health expenditures on immunisation. Assuming no real budget increases, immunisation would account for around 10% in 2022. Vaccines represented 1% of government, non-personnel expenditures for health in 2014, and would be 6% in 2022, assuming no real budget increases. CONCLUSION: While the introduction of new vaccines is justified by expected positive health impacts, long-term affordability will be challenging in light of the current economic climate in Zambia. The government needs to both allocate more resources to the health sector and seek efficiency gains within service provision. PMID- 27371103 TI - Efficacy of various Marek's disease vaccines protocols for prevention of Marek's disease virus-induced immunosuppression. AB - Marek's disease virus (MDV) induces tumors and severe immunosuppression in chickens. MDV-induced immunosuppression (MDV-IS) is very complex and difficult to study. In particular, the late MDV-IS (late-MDV-IS) is of great concern since it can occur in the absence of lymphoid organ atrophy or gross tumors. We have recently developed a model to reproduce late-MDV-IS under laboratory conditions. This model measures MDV-IS indirectly by assessing the effect of MDV infection on the efficacy of infectious laryngotracheitis (ILT) vaccination; hence the name late-MDV-IS ILT model. In this study, we have used the late-MDV-IS ILT model to evaluate if MD vaccination can protect against late-MDV-IS. One experiment was conducted to determine whether serotype 1 MD vaccines (CVI988 and Md5DeltaMEQ) could induce late-MDV-IS by themselves. Three additional experiments were conducted to evaluate efficacy of different MD vaccines (HVT, HVT+SB-1, CVI988, and Md5DeltaMEQ) and different vaccine protocols (day-old vaccination, in ovo vaccination, and double vaccination) against late-MDV-IS. Our results show that none of the currently used vaccine protocols (HVT, HVT+SB-1, or CVI988 administered at day of age, in ovo, or in double vaccination protocols) protected against late-MDV-IS induced by vv+MDV strains 648A and 686. Experimental vaccine Md5DeltaMEQ administered subcutaneously at one day of age was the only vaccine protocol that significantly reduced late-MDV-IS induced by vv+MDV strain 686. This study demonstrates that currently used vaccine protocols confer high levels of protection against MDV-induced tumors (protection index=100), but do not protect against late-MDV-IS; thus, commercial poultry flocks could suffer late MDV-IS even in complete absence of tumors. Our results suggest that MDV-IS might not be related to the development of tumors and novel control methods are needed. Further evaluation of the experimental vaccine Md5DeltaMEQ might shed light on protective mechanisms against late-MDV-IS. PMID- 27371104 TI - Low DNA Sequence Diversity of the Intergenic Spacer 1 Region in the Human Skin Commensal Fungi Malassezia sympodialis and M. dermatis Isolated from Patients with Malassezia-Associated Skin Diseases and Healthy Subjects. AB - As DNA sequences of the intergenic spacer (IGS) region in the rRNA gene show remarkable intraspecies diversity compared with the small subunit, large subunit, and internal transcribed spacer region, the IGS region has been used as an epidemiological tool in studies on Malassezia globosa and M. restricta, which are responsible for the exacerbation of atopic dermatitis (AD) and seborrheic dermatitis (SD). However, the IGS regions of M. sympodialis and M. dermatis obtained from the skin of patients with AD and SD, as well as healthy subjects, lacked sequence diversity. Of the 105 M. sympodialis strains and the 40 M. dermatis strains, the sequences of 103 (98.1 %) and 39 (97.5 %), respectively, were identical. Thus, given the lack of intraspecies diversity in the IGS regions of M. sympodialis and M. dermatis, studies of the diversity of these species should be performed using appropriate genes and not the IGS. PMID- 27371105 TI - The Adaptome: Advancing the Science of Intervention Adaptation. AB - In the past few decades, prevention scientists have developed and tested a range of interventions with demonstrated benefits on child and adolescent cognitive, affective, and behavioral health. These evidence-based interventions offer promise of population-level benefit if accompanied by findings of implementation science to facilitate adoption, widespread implementation, and sustainment. Though there have been notable examples of successful efforts to scale up interventions, more work is needed to optimize benefit. Although the traditional pathway from intervention development and testing to implementation has served the research community well-allowing for a systematic advance of evidence-based interventions that appear ready for implementation-progress has been limited by maintaining the hypothesis that evidence generation must be complete prior to implementation. This sets up the challenging dichotomy between fidelity and adaptation and limits the science of adaptation to findings from randomized trials of adapted interventions. The field can do better. This paper argues for the development of strategies to advance the science of adaptation in the context of implementation that would more comprehensively describe the needed fit between interventions and their settings, and embrace opportunities for ongoing learning about optimal intervention delivery over time. Efforts to build the resulting adaptome (pronounced "adapt-ohm") will include the construction of a common data platform to house systematically captured information about variations in delivery of evidence-based interventions across multiple populations and contexts, and provide feedback to intervention developers, as well as the implementation research and practice communities. Finally, the article identifies next steps to jumpstart adaptome data platform development. PMID- 27371106 TI - Effectiveness of Goal-Setting Telephone Follow-Up on Health Behaviors of Patients with Ischemic Stroke: A Randomized Controlled Trial. AB - BACKGROUND: Adopting healthy behaviors is critical for secondary stroke prevention, but many patients fail to follow national guidelines regarding diet, exercise, and abstinence from risk factors. Compliance often decreases with time after hospital discharge, yet few studies have examined programs promoting long term adherence to health behaviors. Goal setting and telephone follow-up have been proven to be effective in other areas of medicine, so this study evaluated the effectiveness of a guideline-based, goal-setting telephone follow-up program for patients with ischemic stroke. METHODS: This was a multicenter, assessor blinded, parallel-group, randomized controlled trial. Ninety-one stroke patients were randomized to either a control group or an intervention group. Intervention consisted of predischarge education and 3 goal-setting follow-up sessions conducted by phone. Data were collected at baseline and during the third and sixth months after hospital discharge. RESULTS: Six months after discharge, patients in the intervention group exhibited significantly higher medication adherence than patients in the control group. There were no statistically significant differences in physical activity, nutrition, low-salt diet adherence, blood pressure monitoring, smoking abstinence, unhealthy use of alcohol, and modified Rankin Scale (mRS) scores between the 2 groups. CONCLUSIONS: Goal setting telephone follow-up intervention for ischemic stroke patients is feasible and leads to improved medication adherence. However, the lack of group differences in other health behavior subcategories and in themRS score indicates a need for more effective intervention strategies to help patients reach guideline-recommended targets. PMID- 27371108 TI - MicroRNA-506 is up-regulated in the development of pancreatic ductal adenocarcinoma and is associated with attenuated disease progression. AB - BACKGROUND: MicroRNA-506 (miR-506) has been reported to function in several tumors as a tumor suppressor gene or oncogene. However, the expression and role of miR-506 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, we aimed to evaluate the phenotype of miR-506 in PDAC. METHODS: Using miRNA in situ hybridization, we examined the expression of miR-506 in 113 PDACs and 87 paired normal pancreatic tissues. We evaluated miR-506 expression in PDAC cells, normal pancreatic ducts, and acinus/islands, and we analyzed the associations between miR-506 expression and the clinicopathologic characteristics of PDAC patients. RESULTS: miR-506 expression was higher in PDAC than in matched normal pancreatic ductal cells (P < 0.001). On the other hand, the combined group of well and moderately differentiated PDACs showed higher levels of miR-506 than the poorly differentiated ones (P = 0.023). Moreover, miR-506 expression was negatively associated with pathologic T category (P = 0.004) and lymph node metastasis (P = 0.033), suggesting that miR-506 might inhibit the progression of PDAC. CONCLUSIONS: Our results suggest that miR-506 either plays a role as an oncogene in the tumorigenesis and a tumor suppressor in the progression or serves as a house-keeping, tumor-suppressing miRNA, whose expression can be activated by oncogenic signals in early development to hinder the progression of PDAC. PMID- 27371109 TI - Hydroxychalcone inhibitors of Streptococcus mutans glucosyl transferases and biofilms as potential anticaries agents. AB - Streptococcus mutans has been implicated as the major etiological agent in the initiation and the development of dental caries due to its robust capacity to form tenacious biofilms. Ideal therapeutics for this disease will aim to selectively inhibit the biofilm formation process while preserving the natural bacterial flora of the mouth. Several studies have demonstrated the efficacies of flavonols on S. mutans biofilms and have suggested the mechanism of action through their effect on S. mutans glucosyltransferases (Gtfs). These enzymes metabolize sucrose into water insoluble and soluble glucans, which are an integral measure of the dental caries pathogenesis. Numerous studies have shown that flavonols and polyphenols can inhibit Gtf and biofilm formation at millimolar concentrations. We have screened a group of 14 hydroxychalcones, synthetic precursors of flavonols, in an S. mutans biofilm assay. Several of these compounds emerged to be biofilm inhibitors at low micro-molar concentrations. Chalcones that contained a 3-OH group on ring A exhibited selectivity for biofilm inhibition. Moreover, we synthesized 6 additional analogs of the lead compound and evaluated their potential activity and selectivity against S. mutans biofilms. The most active compound identified from these studies had an IC50 value of 44MUM against biofilm and MIC50 value of 468MUM against growth displaying >10-fold selectivity inhibition towards biofilm. The lead compound displayed a dose dependent inhibition of S. mutans Gtfs. The lead compound also did not affect the growth of two commensal species (Streptococcus sanguinis and Streptococcus gordonii) at least up to 200MUM, indicating that it can selectively inhibit cariogenic biofilms, while leaving commensal and/or beneficial microbes intact. Thus non-toxic compounds have the potential utility in public oral health regimes. PMID- 27371107 TI - Immunomodulators in SLE: Clinical evidence and immunologic actions. AB - Systemic lupus erythematosus (SLE) is a potentially fatal autoimmune disease. Current treatment strategies rely heavily on corticosteroids, which are in turn responsible for a significant burden of morbidity, and immunosuppressives which are limited by suboptimal efficacy, increased infections and malignancies. There are significant deficiencies in our immunosuppressive armamentarium, making immunomodulatory therapies crucial, offering the opportunity to prevent disease flare and the subsequent accrual of damage. Currently available immunomodulators include prasterone (synthetic dehydroeipandrosterone), vitamin D, hydroxychloroquine and belimumab. These therapies, acting via numerous cellular and cytokine pathways, have been shown to modify the aberrant immune responses associated with SLE without overt immunosuppression. Vitamin D is important in SLE and supplementation appears to have a positive impact on disease activity particularly proteinuria. Belimumab has specific immunomodulatory properties and is an effective therapy in those with specific serological and clinical characteristics predictive of response. Hydroxychloroquine is a crucial background medication in SLE with actions in many molecular pathways. It has disease specific effects in reducing flare, treating cutaneous disease and inflammatory arthralgias in addition to other effects such as reduced thrombosis, increased longevity, improved lipids, better glycemic control and blood pressure. Dehydroeipandrosterone is also an immunomodulator in SLE which can have positive effects on disease activity and has bone protective properties. This review outlines the immunologic actions of these drugs and the clinical evidence supporting their use. PMID- 27371110 TI - Design, synthesis and anticancer activity of novel hybrid compounds between benzofuran and N-aryl piperazine. AB - A series of novel hybrid compounds between benzofuran and N-aryl piperazine have been designed and prepared. These derivatives were evaluated for their in vitro anti-tumor activity against a panel of human tumor cell lines by MTT assay. The results demonstrated that amide derivatives were more bioactive than sulfonamide compounds in general, and that chloro or trifluoromethyl substituent was vital for modulating cytotoxic activity. In particular, compound 13 was found to be the most potent compound against 4 strains human tumor cell lines, and exhibited cytotoxic activity selectively against Hela (0.03MUM). PMID- 27371111 TI - Circadian control of prothoracicotropic hormone release in an adult insect and the induction of its rhythmicity by light cues. AB - The insect neuropeptide prothoracicotropic hormone (PTTH) is a critical regulator of larval development. We recently demonstrated that PTTH is also present in adult Rhodnius prolixus and is released by adult brains in vitro with a clear daily rhythm during egg development. Here, we employ a well-established in vitro bioassay, to show that the daily rhythm of PTTH release by brains in vitro is under circadian control since it persists in aperiodic conditions with a free running period of around 24h that is temperature compensated. Prolonged exposure (3weeks) of insects to continuous constant light (LL) completely eliminated PTTH release. Subsequent transfer of such insects from LL to constant darkness (DD) rapidly induced rhythmic PTTH release, indicating that the circadian rhythm of PTTH release is induced by photic cues. Western analysis identified PTTH in the adult hemolymph, suggesting that PTTH acts as a functional neurohormone in the adult insect. Dot blot analysis revealed that PTTH levels in the hemolymph also cycled with a daily rhythm that persisted in DD and was synchronous with the rhythm of PTTH release by brains in vitro. We conclude that the previously documented photosensitive clock in the brain regulates rhythmic PTTH release and thus generates the rhythm seen in the hemolymph. These results emphasize the importance of rhythmic PTTH release in the adult insect and support a role for PTTH in adult physiology and possibly within the adult circadian system. PMID- 27371112 TI - Are mussels able to distinguish underwater sounds? Assessment of the reactions of Mytilus galloprovincialis after exposure to lab-generated acoustic signals. AB - This study examined the effects of lab-generated acoustic signals on the behaviour and biochemistry of Mediterranean mussels (Mytilus galloprovincialis). The experiment was carried out in a tank equipped with a video-recording system using six groups of five mussels exposed to five acoustic treatments (each treatment was replicated three times) for 30min. The acoustic signals, with a maximum sound pressure level of 150dB rms re 1MUPa, differed in frequency range as follows: low (0.1-5kHz), mid-low (5-10kHz), mid (10-20kHz), mid-high (20 40kHz) and high (40-60kHz). The exposure to sweeps did not produce any significant changes in the mussels' behaviour. Conversely, the specimens exposed to the low frequency band treatment showed significantly higher values of the following biochemical stress parameters measured in their plasma and tissues: glucose, total proteins, total haemocyte number (THC), heat shock protein 70 (Hsp70) expression, and Acetylcholinesterase (AChE) activity. The responses observed in the mussels exposed to low frequency sweeps enable us to suppose a biological and ecological role for this sound, which contains the main frequencies produced by both shipping traffic and the acoustic emissions of fish. PMID- 27371113 TI - Defining the allometric relationship between size and individual fatty acid turnover in barramundi Lates calcarifer. AB - An experiment was conducted with barramundi (Asian seabass; Lates calcarifer) to examine the allometric scaling effect of individual fatty acids. Six treatment size classes of fish were deprived of food for 21days (Treatment A, 10.5+/-0.13g; Treatment B, 19.2+/-0.11g; Treatment C, 28.3+/-0.05g; Treatment D, 122.4+/-0.10g; Treatment E, 217.6+/-0.36g; Treatment F, 443.7+/-1.48g; mean+/-SD) with each treatment comprising of fifteen fish, in triplicate. The assessment of somatic losses of whole-body energy and lipid were consistent with previous studies, validating the methodology to be extended to individual fatty acids. Live-weight (LW) exponent values were determined to be 0.817+/-0.010 for energy and 0.895+/ 0.007 for lipid. There were significant differences among the fatty acids ranging from 0.687+/-0.005 for 20:5n-3 (eicosapentaenoic acid) and 0.954+/-0.008 for 18:1n-9 (oleic acid). The LW exponent values were applied to existing fatty acid intake and deposition data of barramundi fed with either 100% fish oil or 100% poultry oil. From this the maintenance requirement for each fatty acid was determined. The metabolic demands for maintenance and growth were then iteratively determined for fish over a range of size classes. Application of these exponent values to varying levels of fatty acid intake demonstrated that the biggest driver in the utilisation of fatty acids in this species is deposition demand and despite their reputed importance, the long-chain polyunsaturated fatty acids had nominal to no maintenance requirement. PMID- 27371114 TI - Higher rates of aneuploidy in blastocysts and higher risk of no embryo transfer in recurrent pregnancy loss patients with diminished ovarian reserve undergoing in vitro fertilization. AB - OBJECTIVE: To study the prediction of aneuploidy rate in blastocysts from patients with recurrent pregnancy loss (RPL) on the basis of ovarian reserve testing. DESIGN: Prospective cohort analysis. SETTING: Private, university affiliated fertility clinic. PATIENT(S): A total of 239 patients with RPL, defined as two or more clinical miscarriages, were screened for inclusion. One hundred two (102) cycles in patients with unexplained RPL resulted in at least one euploid embryo transferred. Outcomes were compared by ovarian reserve test results, with diminished ovarian reserve (DOR) defined as a cycle day 3 FSH >10 IU/mL and/or antimullerian hormone <1 ng/mL. INTERVENTION(S): In vitro fertilization with blastocyst biopsy and aneuploidy screening of all 23 chromosome pairs. MAIN OUTCOME MEASURE(S): Rate of aneuploidy in blastocysts and incidence of IVF cycles with no transfer owing to no euploid blasts. RESULT(S): Patients with DOR had a higher percentage of aneuploid blastocysts (57% vs 49%) and a higher incidence of no euploid embryos to transfer (25% vs 13%). The higher rate of aneuploidy in blastocysts was most significant in patients aged <38 years (67% vs 53%). Implantation rates after transfer of euploid blastocysts were similar (61% compared with 59%), and miscarriage rates were low (14% and 10%). CONCLUSION(S): Unexplained RPL patients with DOR have a higher percentage of aneuploid blastocysts and risk of no euploid embryo to transfer compared with unexplained RPL patients with normal ovarian reserve testing. The difference is most significant in patients aged <38 years. Patients with RPL and DOR with euploid embryo transferred had similar outcomes compared with patients with RPL and normal ovarian reserve testing. PMID- 27371115 TI - Survival studies of a temperate and lytic bacteriophage in bovine faeces and slurry. AB - AIMS: Cattle are the main reservoir of verocytotoxigenic Escherichia coli (VTEC), food-borne pathogens that express verocytotoxins (vtx) encoded by temperate bacteriophage. Bovine faeces and unturned manure heaps can support the survival of VTEC and may propagate and transmit VTEC. This study investigated the survival of a vtx2 bacteriophage, phi24B ::Kan, in bovine faeces and slurry. The survival of an anti-Escherichia coli O157:H7 lytic bacteriophage, e11/2, was examined in the same matrices, as a possible bio-control option for VTEC. METHODS AND RESULTS: Samples were inoculated with phi24B ::Kan and/or e11/2 bacteriophage at a concentration of 7-8 log10 PFU g(-1) (faeces) or ml(-1) (slurry), stored at 4 and 14 degrees C and examined every 2 days for 36 days. The ability of phi24B ::Kan to transduce E. coli cells was examined. Moreover, E. coli concentrations in the faeces and slurry were monitored throughout the experiment as were the pH and aw (faeces only). Both bacteriophages survived well in faeces and slurry. In addition, phi24B ::Kan was able to form lysogens. CONCLUSIONS: phi24B ::Kan and e11/2 phage can survive and remain infective in bovine faeces and slurry for at least 30 days under representative Irish temperatures. SIGNIFICANCE AND IMPACT OF THE STUDY: Bovine faeces and slurry may act as a reservoir for vtx bacteriophages. The survival of the anti-O157 phage suggests it may be a suitable bio-control option in these matrices. PMID- 27371116 TI - Preclinical assessment of a new recombinant ADAMTS-13 drug product (BAX930) for the treatment of thrombotic thrombocytopenic purpura. AB - Essentials ADAMTS-13-deficiency is a cause of thrombotic thrombocytopenic purpura (TTP). Preclinical safety of recombinant human ADAMTS-13 (BAX930) was shown in animal models. Preclinical efficacy of BAX930 was shown in a mouse model of TTP. BAX930 showed advantageous efficacy over fresh frozen plasma, the current standard of care. Click to hear Dr Cataland and Prof. Lammle present a seminar on Thrombotic Thrombocytopenic Purpura (TTP): new Insights in Pathogenesis and Treatment Modalities. SUMMARY: Background Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder characterized by microthrombosis in small blood vessels of the body, resulting in a low platelet count. Baxalta has developed a new recombinant ADAMTS-13 (rADAMTS-13) product (BAX930) for on-demand and prophylactic treatment of patients with hereditary TTP (hTTP). Objectives To evaluate the pharmacokinetics, efficacy and safety of BAX930 in different species, by use of an extensive preclinical program. Methods The prophylactic and therapeutic efficacies of BAX930 were tested in a previously established TTP mouse model. Pharmacokinetics were evaluated after single intravenous bolus injection in mice and rats, and after repeated dosing in cynomolgus monkeys. Toxicity was assessed in rats and monkeys, safety pharmacology in monkeys, and local tolerance in rabbits. Results BAX930 was shown to be efficacious, as demonstrated by a stabilized platelet count in ADAMTS-13 knockout mice that were thrombocytopenic when treated. Prophylactic efficacy was dose-dependent and comparable with that achieved by treatment with fresh frozen plasma, the mainstay of hTTP treatment. Therapeutic efficacy was treatment interval-dependent. Safety pharmacology evaluation did not show any deleterious effects of BAX930 on cardiovascular and respiratory functions in monkeys. The compound's pharmacokinetics were similar and dose-proportional in mice, rats, and monkeys. BAX930 was well tolerated in rats, monkeys, and rabbits, even at the highest doses tested. Conclusions These results demonstrate that BAX930 has a favorable preclinical profile, and support the clinical development of rADAMTS-13 for the treatment of hTTP. PMID- 27371117 TI - Transcription Termination: Variations on Common Themes. AB - Transcription initiates pervasively in all organisms, which challenges the notion that the information to be expressed is selected mainly based on mechanisms defining where and when transcription is started. Together with post transcriptional events, termination of transcription is essential for sorting out the functional RNAs from a plethora of transcriptional products that seemingly have no use in the cell. But terminating transcription is not that easy, given the high robustness of the elongation process. We review here many of the strategies that prokaryotic and eukaryotic cells have adopted to dismantle the elongation complex in a timely and efficient manner. We highlight similarities and diversity, underlying the existence of common principles in a diverse set of functionally convergent solutions. PMID- 27371118 TI - Disturbance of mitochondrial functions provoked by the major long-chain 3 hydroxylated fatty acids accumulating in MTP and LCHAD deficiencies in skeletal muscle. AB - The pathogenesis of the muscular symptoms and recurrent rhabdomyolysis that are commonly manifested in patients with mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiencies is still unknown. In this study we investigated the effects of the major long-chain monocarboxylic 3-hydroxylated fatty acids (LCHFA) accumulating in these disorders, namely 3-hydroxytetradecanoic (3HTA) and 3-hydroxypalmitic (3HPA) acids, on important mitochondrial functions in rat skeletal muscle mitochondria. 3HTA and 3HPA markedly increased resting (state 4) and decreased ADP-stimulated (state 3) and CCCP-stimulated (uncoupled) respiration. 3HPA provoked similar effects in permeabilized skeletal muscle fibers, validating the results obtained in purified mitochondria. Furthermore, 3HTA and 3HPA markedly diminished mitochondrial membrane potential, NAD(P)H content and Ca(2+) retention capacity in Ca(2+)-loaded mitochondria. Mitochondrial permeability transition (mPT) induction probably underlie these effects since they were totally prevented by cyclosporin A and ADP. In contrast, the dicarboxylic analogue of 3HTA did not alter the tested parameters. Our data strongly indicate that 3HTA and 3HPA behave as metabolic inhibitors, uncouplers of oxidative phosphorylation and mPT inducers in skeletal muscle. It is proposed that these pathomechanisms disrupting mitochondrial homeostasis may be involved in the muscle alterations characteristic of MTP and LCHAD deficiencies. PMID- 27371119 TI - [Mitochondrial Neuro-Gastro-Intestinal Encephalopathy (MNGIE): When and how to suspect it in front of an atypical anorexia nervosa?] AB - INTRODUCTION: The Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE) disease is an extremely underrated syndrome beginning around the age of eighteen years. Because of its severity, this diagnosis should be considered when a patient presents an atypical anorexia nervosa. MNGIE disease is inherited in an autosomal recessive manner and related to mutations of the TYMP gene (ch22q13.32 qter), encoding the thymidine phosphorylase. The MNGIE is often misdiagnosed and is associated with a time to diagnostic of about 12 years after first symptoms. Thus this critical review aims to help clinicians better identify symptoms and paraclinical markers of the MNGIE as a differential diagnosis of atypical anorexia nervosa. METHODS: A literature search was performed using PubMed and Google Scholar databases. RESULTS: The clinical diagnosis of the MNGIE disease should be based on the association of severe loss of weight and some additional symptoms: (1) severe gastrointestinal dysmotility (nausea, vomiting, intestinal pseudo-obstruction), (2) ptosis or external ophtalmoplegia and (3) peripheral sensorimotor neuropathy. When MNGIE disease is clinically suspected, paraclinical testing can help to validate the MNGIE diagnostic: (1) Arterial blood test reveals lactic acidemia (e.g. an increased serum concentration of lactate without pH modifications), and (2) Brain MRI indicates leukoencephalopathy, usually asymptomatic. Direct evidence of MNGIE disease is based on specific testing of: (1) the thymidine phopshorylase enzyme activity in leukocytes is less than 10% of the control, (2) the increase of plasmatic thymidine (>3MUmol/L) and the increase of plamatic deoxyuridine (>5MUmol/L), (3) the evidence of mutations of the TYMP gene by molecular genetic testing. CONCLUSION: The MNGIE disease is a severe trouble with multisystemic complications. The thymidine phopshorylase enzyme activity in leukocytes should be measured as soon as possible when a patient presents atypical anorexia nervosa. PMID- 27371120 TI - [Psychotherapic interventions for bipolar disorder in children and adolescents]. AB - OBJECTIVE: To review the options for psychosocial interventions in pediatric bipolar disorders. METHODS: A comprehensive literature review of randomized clinical trials and open-label studies was conducted. RESULTS: Randomized controlled trials show that psychosocial interventions involving families (i.e. family-focused treatment) or individual and family therapy (i.e. multi- or individual-family psychoeducational psychotherapy, child- and family-focused cognitive-behavioral therapy, dialectical behavior therapy) may be effective through added benefit to pharmacotherapy. All these interventions share numerous common therapeutic elements such as psychoeducation and skills training. Individual interventions (i.e. interpersonal and social rhythm therapy and cognitive-behavioral therapy) are to date less well documented. However that may be, outcome studies remain few, and numerous methodological limitations (small sample sizes, designs not very rigorous) restrict the interpretability and generalisability of their results. In addition, most studies were conducted in specialty centers with highly trained therapists, and the feasibility and acceptability of these interventions in practice settings remain to be shown. CONCLUSION: Despite recent developments in identifying effective psychosocial interventions, numerous critical gaps remain, and more longitudinal studies are needed to clarify how these interventions work. PMID- 27371122 TI - [Not Available]. PMID- 27371121 TI - Single molecule studies of helicases with magnetic tweezers. AB - Helicases are a broad family of enzymes that perform crucial functions in DNA replication and in the maintenance of DNA and RNA integrity. A detailed mechanical study of helicases on DNA and RNA is possible using single molecule manipulation methods. Among those, magnetic tweezers (or traps) present a convenient, moderate throughput assay (tens of enzymes can be monitored simultaneously) that allow for high resolution (single base-pair) studies of these enzymes in various conditions and on various substrates (double and single stranded DNA and RNA). Here we discuss various implementation of the basic assay relevant for these studies. PMID- 27371123 TI - [Not Available]. PMID- 27371124 TI - [Not Available]. PMID- 27371125 TI - [Not Available]. PMID- 27371126 TI - [Not Available]. PMID- 27371127 TI - [Not Available]. PMID- 27371128 TI - [Not Available]. PMID- 27371129 TI - [Not Available]. PMID- 27371130 TI - [Not Available]. PMID- 27371131 TI - Seizures and psychiatric manifestations heralding Biermer's disease. PMID- 27371133 TI - Posterior reversible encephalopathy syndrome revealing acute intermittent porphyria. PMID- 27371132 TI - Posterior reversible encephalopathy syndrome (PRES) and hypomagnesemia: A frequent association? AB - Posterior reversible encephalopathy syndrome (PRES) is a serious neurological condition encountered in various medical fields. Pathophysiological factor(s) common to PRES cases of apparently unrelated etiologies are yet to be found. Based on the hypothesis that hypomagnesemia might participate in the cascade leading to PRES, our study sought to verify whether hypomagnesemia is frequently associated with PRES regardless of etiology. From a retrospective study of a cohort of 57 patients presenting with PRES of different etiologies, presented here are the findings of 19 patients with available serum magnesium levels (SMLs) during PRES. In the acute phase of PRES, hypomagnesemia was present in all 19 patients in spite of differences in etiology (including immunosuppressive drugs, hypertensive encephalopathy, eclampsia, systemic lupus erythematosus, iatrogenic etiology and unknown). SMLs were within normal ranges prior to PRES and below normal ranges during the first 48h of PRES, with a significant decrease in SMLs during the acute phase. In this retrospective study, constant hypomagnesemia was observed during the acute phase of PRES regardless of its etiology. These results now require larger studies to assess the particular importance of acute hypomagnesemia in PRES and especially the possible need to treat PRES with magnesium sulfate. PMID- 27371134 TI - Immunologic Targets in Atopic Dermatitis and Emerging Therapies: An Update. AB - Atopic dermatitis is one of the most common chronic inflammatory skin diseases. It usually begins in childhood, has a considerable impact on patients' quality of life, and incurs substantial healthcare costs. The standard-of-care treatments for patients with moderate to severe disease are very limited and have variable and typically insufficient efficacy and many side effects, some of which are quite serious. However, over the last decade, considerable advances in our understanding of the pathogenesis of atopic dermatitis have paved the way for a number of new treatments. Most notable are the drugs that target the Th2 polarized immune system, which is thought to play a key role in many of the signs and symptoms characteristic of this disease. In this article, we briefly review the pathophysiology of atopic dermatitis, while noting that each patient's disease phenotype is likely due to a unique interplay of several disease-specific dysregulated pathways. Lastly, we cover emerging therapies for atopic dermatitis, focusing on those that target specific components of the immune system, which are altered in atopic dermatitis. The hope is that these new biologics or small molecule antagonists, which have high specificity for their target molecules, will decrease the undesirable side effects caused by off-target effects commonly observed with current immunosuppressive agents that are characterized by broad biological actions. PMID- 27371135 TI - Toward isolating the role of dopamine in the acquisition of incentive salience attribution. AB - Stimulus-reward learning has been heavily linked to the reward-prediction error learning hypothesis and dopaminergic function. However, some evidence suggests dopaminergic function may not strictly underlie reward-prediction error learning, but may be specific to incentive salience attribution. Utilizing a Pavlovian conditioned approach procedure consisting of two stimuli that were equally reward predictive (both undergoing reward-prediction error learning) but functionally distinct in regard to incentive salience (levers that elicited sign-tracking and tones that elicited goal-tracking), we tested the differential role of D1 and D2 dopamine receptors and nucleus accumbens dopamine in the acquisition of sign- and goal-tracking behavior and their associated conditioned reinforcing value within individuals. Overall, the results revealed that both D1 and D2 inhibition disrupted performance of sign- and goal-tracking. However, D1 inhibition specifically prevented the acquisition of sign-tracking to a lever, instead promoting goal-tracking and decreasing its conditioned reinforcing value, while neither D1 nor D2 signaling was required for goal-tracking in response to a tone. Likewise, nucleus accumbens dopaminergic lesions disrupted acquisition of sign tracking to a lever, while leaving goal-tracking in response to a tone unaffected. Collectively, these results are the first evidence of an intraindividual dissociation of dopaminergic function in incentive salience attribution from reward-prediction error learning, indicating that incentive salience, reward-prediction error, and their associated dopaminergic signaling exist within individuals and are stimulus-specific. Thus, individual differences in incentive salience attribution may be reflective of a differential balance in dopaminergic function that may bias toward the attribution of incentive salience, relative to reward-prediction error learning only. PMID- 27371136 TI - Changes in Substance Use Symptoms Across Adolescence in Youth Perinatally Infected with HIV. AB - The paper utilizes data collected at three time points in a longitudinal study of perinatally HIV-infected (PHIV+) and a comparison group of perinatally exposed but HIV-uninfected (PHEU) youths in the United States (N = 325). Using growth curve modeling, the paper examines changes in substance use symptoms among PHIV+ and PHEU youths as they transition through adolescence, and assesses the individual and contextual factors associated with the rate of change in substance use symptoms. Findings indicate that substance use symptoms increased over time among PHIV+ youths, but not among PHEU youths. The rate of change in these symptoms was positively associated with an increasing number of negative life events. Study findings underscore the need for early, targeted interventions for PHIV+ youths, and interventions to reduce adversities and their deleterious effects in vulnerable populations. PMID- 27371137 TI - Lake drying and livelihood dynamics in Lake Chad: Unravelling the mechanisms, contexts and responses. AB - This article examines lake drying and livelihood dynamics in the context of multiple stressors through a case study of the "Small Lake Chad" in the Republic of Chad. Livelihoods research in regions experiencing persistent lake water fluctuations has largely focused on the well-being and security of lakeshore dwellers. Little is known about the mechanisms through which lake drying shapes livelihood drawbacks and opportunities, and whether locally evolved responses are enhancing livelihoods. Here we address these gaps using empirical, mixed-methods field research couched within the framework of livelihoods and human well-being contexts. The analysis demonstrates that limited opportunities outside agriculture, the influx of mixed ethnic migrants and the increasing spate of violence all enhance livelihood challenges. Livelihood opportunities centre on the renewal effects of seasonal flood pulses on lake waters and the learning opportunities triggered by past droughts. Although drying has spurred new adaptive behaviours predicated on seasonality, traditional predictive factors and the availability of assets, responses have remained largely reactive. The article points to where lake drying fits amongst changes in the wider socio-economic landscape in which people live, and suggests that awareness of the particularities of the mechanisms that connect lake drying to livelihoods can offer insights into the ways local people might be assisted by governments and development actors. PMID- 27371139 TI - A Developmental Perspective of Global and Local Visual Perception in Autism Spectrum Disorder. AB - Individuals with autism spectrum disorder (ASD) demonstrate superior performances on visuo-spatial tasks emphasizing local information processing; however, findings from studies involving hierarchical stimuli are inconsistent. Wide age ranges and group means complicate their interpretability. Children and adolescents with and without ASD completed a Navon task wherein they identified global and local stimuli composed of either consistent or inconsistent letters. Trajectories of reaction time in global and local conditions were similar within and between groups when consistent and inconsistent stimuli were considered together, but the effect of local-to-global interference was significantly higher in participants with than without ASD. Age was not a significant predictor of local-to-global interference, suggesting that this effect emerges in childhood and persists throughout adolescence in ASD. PMID- 27371138 TI - Sociomoral Reasoning, Empathy, and Meeting Developmental Tasks During the Transition to Adulthood in Autism Spectrum Disorder. AB - This mixed methods study investigated sociomoral reasoning, empathy, and challenging and supportive factors during the transition to adulthood in emerging adults (18-27-years-old) with autism spectrum disorder (ASD) to better understand how these variables facilitated positive developmental outcomes. Same-aged ASD (n = 22) and typically developing (TD) (n = 22) groups completed quantitative and qualitative measures assessing these constructs. Compared to the TD group, the ASD group had significantly lower sociomoral reasoning and perspective-taking, significantly higher personal distress, but similar empathic concern. Inductive content analysis showed those with ASD and better developmental outcomes more often discussed the value of informal social support and utilized perspective taking during challenging sociomoral situations. PMID- 27371140 TI - [Not Available]. PMID- 27371142 TI - [Not Available]. PMID- 27371141 TI - [Not Available]. PMID- 27371144 TI - [Not Available]. PMID- 27371143 TI - [Not Available]. PMID- 27371145 TI - [Not Available]. PMID- 27371146 TI - [Not Available]. PMID- 27371148 TI - [Not Available]. PMID- 27371147 TI - [Not Available]. PMID- 27371149 TI - [Not Available]. PMID- 27371151 TI - [Not Available]. PMID- 27371150 TI - [Not Available]. PMID- 27371152 TI - [Not Available]. PMID- 27371153 TI - [Not Available]. PMID- 27371154 TI - [Not Available]. PMID- 27371155 TI - [Not Available]. PMID- 27371156 TI - [Not Available]. PMID- 27371157 TI - Task-related fMRI responses to a nicotinic acetylcholine receptor partial agonist in schizophrenia: A randomized trial. AB - INTRODUCTION: AQW051, an alpha7-nicotinic acetylcholine receptor partial agonist, enhanced cognitive function in rodent models of learning and memory. This study evaluated brain activation during performance of a working memory task (WMT) and an episodic memory task (EMT), and the effect of AQW051 on task-related brain activation and performance in subjects with schizophrenia. METHODS: This was a double-blind, randomized, placebo-controlled, multicenter, 2-period cross-over trial (NCT00825539) in participants with chronic, stable schizophrenia. Participants, stratified according to smoking status, were randomized (1:1:1:1:1:1) to 1 of 6 sequence groups that determined the study drug dose (AQW051 7.5mg, 50mg or 100mg) and order of administration versus placebo. The primary outcome was brain activation in a priori target regions of interest (ROIs) during performance of the WMT and EMT, measured using functional magnetic resonance imaging. The effect of AQW051 on task-related (EMT and WMT) brain activation and performance was also assessed, as were safety and tolerability. RESULTS: Overall, 60 of 68 enrolled participants completed the study (AQW051 then placebo: 7.5mg n=9; 50mg n=11; 100mg n=10. Placebo then AQW051: 7.5mg n=10; 50mg n=11; 100mg n=9). Significant task-related brain activation (5% significance level) was observed with placebo. During the WMT, a medium effect size was observed in the inferior prefrontal cortex with AQW051 100mg versus placebo (0.431; p=0.105). During the EMT encoding phase, a large effect size was observed in the anterior hippocampus (0.795; p=0.007) and a medium effect size in the posterior hippocampus (0.476; p=0.079) with AQW051 7.5mg. No other medium/large effect sizes were observed with any dose on either task. Effects on brain activation were generally not associated with changes in cognitive performance. AQW051 was well tolerated with an acceptable safety profile. CONCLUSIONS: Overall, no consistent effects of AQW051 on brain regions involved in the performance of a WMT or EMT were observed; however, this study presents a model for evaluating potential response to pharmacological interventions for cognitive impairment in schizophrenia. PMID- 27371158 TI - Role of antigen presenting cell invariant chain in the development of hepatic steatosis in mouse model. AB - The role of Invariant chain (CD74 or Ii) in antigen presentation via Antigen Presenting Cells (APC), macrophage recruitment as well as survival, T cell activation and B cell differentiation has been well recognized. However, the aspect of CD74 which is involved in the development of hepatic steatosis and the pathways through which it acts remain to be studied. In this study, we investigated the role of CD74 in the inflammatory pathway and its contribution to development of hepatic steatosis. For this, wild type C57BL/6J and CD74 deficient mice (Ii(-/-) mice) were fed with high fat high fructose (HFHF) diet for 12 weeks. Chronic consumption of this feed did not develop hepatic steatosis, glucose intolerance or change in the level of immune cells in Ii(-/-) mice. Moreover, there was relatively delayed expression of genes involved in development of non alcoholic fatty liver disease (NAFLD) in HFHF fed Ii(-/-) mice as compared to that of C57BL/6J phenotype. Taken together, the data suggest that HFHF diet fed Ii(-/-) mice fail to develop hepatic steatosis, suggesting that Ii mediated pathways play a vital role in the initiation and propagation of liver inflammation. PMID- 27371159 TI - Bystander Effect Induced by Electroporation is Possibly Mediated by Microvesicles and Dependent on Pulse Amplitude, Repetition Frequency and Cell Type. AB - Bystander effect, a known phenomenon in radiation biology, where irradiated cells release signals which cause damage to nearby, unirradiated cells, has not been explored in electroporated cells yet. Therefore, our aim was to determine whether bystander effect is present in electroporated melanoma cells in vitro, by determining viability of non-electroporated cells exposed to medium from electroporated cells and by the release of microvesicles as potential indicators of the bystander effect. Here, we demonstrated that electroporation of cells induces bystander effect: Cells exposed to electric pulses mediated their damage to the non-electroporated cells, thus decreasing cell viability. We have shown that shedding microvesicles may be one of the ways used by the cells to mediate the death signals to the neighboring cells. The murine melanoma B16F1 cell line was found to be more electrosensitive and thus more prone to bystander effect than the canine melanoma CMeC-1 cell line. In B16F1 cell line, bystander effect was present above the level of electropermeabilization of the cells, with the threshold at 800 V/cm. Furthermore, with increasing electric field intensities and the number of pulses, the bystander effect also increased. In conclusion, electroporation can induce bystander effect which may be mediated by microvesicles, and depends on pulse amplitude, repetition frequency and cell type. PMID- 27371160 TI - UCP3 Regulates Single-Channel Activity of the Cardiac mCa1. AB - Mitochondrial Ca(2+) uptake (mCa(2+) uptake) is thought to be mediated by the mitochondrial Ca(2+) uniporter (MCU). UCP2 and UCP3 belong to a superfamily of mitochondrial ion transporters. Both proteins are expressed in the inner mitochondrial membrane of the heart. Recently, UCP2 was reported to modulate the function of the cardiac MCU related channel mCa1. However, the possible role of UCP3 in modulating cardiac mCa(2+) uptake via the MCU remains inconclusive. To understand the role of UCP3, we analyzed cardiac mCa1 single-channel activity in mitoplast-attached single-channel recordings from isolated murine cardiac mitoplasts, from adult wild-type controls (WT), and from UCP3 knockout mice (UCP3(-/-)). Single-channel registrations in UCP3(-/-) confirmed a murine voltage gated Ca(2+) channel, i.e., mCa1, which was inhibited by Ru360. Compared to WT, mCa1 in UCP3(-/-) revealed similar single-channel characteristics. However, in UCP3(-/-) the channel exhibited decreased single-channel activity, which was insensitive to adenosine triphosphate (ATP) inhibition. Our results suggest that beyond UCP2, UCP3 also exhibits regulatory effects on cardiac mCa1/MCU function. Furthermore, we speculate that UCP3 might modulate previously described inhibitory effects of ATP on mCa1/MCU activity as well. PMID- 27371161 TI - The effects of acute stress on core executive functions: A meta-analysis and comparison with cortisol. AB - Core executive functions such as working memory, inhibition, and cognitive flexibility are integral to daily life. A growing body of research has suggested that acute stress may impair core executive functions. However, there are a number of inconsistencies in the literature, leading to uncertainty about how or even if acute stress influences core executive functions. We addressed this by conducting a meta-analysis of acute stress effects on working memory, inhibition, and cognitive flexibility. We found that stress impaired working memory and cognitive flexibility, whereas it had nuanced effects on inhibition. Many of these effects were moderated by other variables, such as sex. In addition, we compared effects of acute stress on core executive functions to effects of cortisol administration and found some striking differences. Our findings indicate that stress works through mechanisms aside from or in addition to cortisol to produce a state characterized by more reactive processing of salient stimuli but greater control over actions. We conclude by highlighting some important future directions for stress and executive function research. PMID- 27371164 TI - Increased MicroRNA-1266 levels as a biomarker for disease activity in psoriasis vulgaris. AB - BACKGROUND: Increasing evidence has shown that serum microRNA (miR) levels are useful biomarkers for the diagnosis, prognosis, and therapeutic value in various diseases. Psoriasis is characterized by a specific miR expression profile, with a characteristic miR signature, distinct from that of healthy skin. OBJECTIVES: To understand the role of miR-1266 in the pathogenesis of psoriasis and to explore if it has the potential as a blood biomarker. We assessed serum miR-1266 levels in patients with psoriasis before and after treatment and compared it with controls. In addition, we evaluated the relationship between miR-1266 and clinical severity in psoriasis before and after treatment. METHODS: miR-1266 was measured using real-time polymerase chain reaction in 35 patients with chronic plaque psoriasis and 35 healthy controls before and after treatment. Moreover, the correlation between miR-1266 levels and psoriasis area and severity index score was determined. RESULTS: Serum miR-1266 levels were considerably higher in patients with psoriasis than in healthy control subjects. Furthermore, miR-1266 levels showed a strong positive correlation with psoriasis area and severity index score before and after treatment, having a marked decline with therapy. CONCLUSION: miR-1266 may have an important role in the pathogenesis of psoriasis vulgaris. This may presumably have possible future implications on the treatment of this chronic disease. PMID- 27371165 TI - [Not Available]. PMID- 27371162 TI - Large-scale production of foot-and-mouth disease virus (serotype Asia1) VLP vaccine in Escherichia coli and protection potency evaluation in cattle. AB - BACKGROUND: Foot-and-mouth disease (FMD) is an acute, highly contagious disease that infects cloven-hoofed animals. Vaccination is an effective means of preventing and controlling FMD. Compared to conventional inactivated FMDV vaccines, the format of FMDV virus-like particles (VLPs) as a non-replicating particulate vaccine candidate is a promising alternative. RESULTS: In this study, we have developed a co-expression system in E. coli, which drove the expression of FMDV capsid proteins (VP0, VP1, and VP3) in tandem by a single plasmid. The co expressed FMDV capsid proteins (VP0, VP1, and VP3) were produced in large scale by fermentation at 10 L scale and the chromatographic purified capsid proteins were auto-assembled as VLPs in vitro. Cattle vaccinated with a single dose of the subunit vaccine, comprising in vitro assembled FMDV VLP and adjuvant, developed FMDV-specific antibody response (ELISA antibodies and neutralizing antibodies) with the persistent period of 6 months. Moreover, cattle vaccinated with the subunit vaccine showed the high protection potency with the 50 % bovine protective dose (PD50) reaching 11.75 PD50 per dose. CONCLUSIONS: Our data strongly suggest that in vitro assembled recombinant FMDV VLPs produced from E. coli could function as a potent FMDV vaccine candidate against FMDV Asia1 infection. Furthermore, the robust protein expression and purification approaches described here could lead to the development of industrial level large-scale production of E. coli-based VLPs against FMDV infections with different serotypes. PMID- 27371163 TI - Endovascular Management of Infected Iliofemoral Pseudoaneurysms: A Case Series. AB - The treatment of infected iliofemoral pseudoaneurysms is challenging and controversial. We present our experience regarding the efficacy and outcome of endovascular treatment of infected iliofemoral arterial pseudoaneurysms with covered stents. Our experience with 5 cases showed that stent grafting combined with antibiotic therapy and provisional drainage may be a safe and effective option in patients with cancer, patients with history of multiple hip revisions, and drug-addicted users. In our small case series, the reinfection rate was null and no covered stent thrombosis occurred. These results are fairly encouraging, but further studies with longer follow-up in a larger number of patients are needed to confirm the efficacy and durability of the technique. PMID- 27371167 TI - [Not Available]. PMID- 27371166 TI - [Not Available]. PMID- 27371168 TI - [Not Available]. PMID- 27371169 TI - [Not Available]. PMID- 27371170 TI - [Not Available]. PMID- 27371172 TI - [Not Available]. PMID- 27371171 TI - [Not Available]. PMID- 27371174 TI - [Experience of a second victims support unit (USVIC)]. PMID- 27371173 TI - Characterization of the binding pattern of human aquaporin-4 autoantibodies in patients with neuromyelitis optica spectrum disorders. AB - BACKGROUND: The discovery of a highly specific antibody against the aquaporin-4 (AQP4) water channel (AQP4-IgG) unified the spectrum of neuromyelitis optica spectrum disorders (NMOSD), which are considered to be antibody-mediated autoimmune diseases. The AQP4 water channel is located on astrocytic end-feet processes and consists of six transmembrane helical domains forming three extracellular loops A, C, and E in which defined amino acids were already proven to be critical for AQP4-IgG binding. However, the clinical relevance of these findings is unclear. Therefore, we have characterized the epitope specificity of AQP4-IgG-positive NMOSD patients. METHODS: We established a cell-based flow cytometry assay for the quantitative detection of AQP4-IgG-positive serum samples. Human embryonic kidney (HEK) cells were transiently transfected with an EmGFP-tagged AQP4-M23, AQP4-M1, or six AQP4-M23 extracellular loop mutants including two mutations in loop A (serial AA substitution, insertion of a myc tag), two in loop C (N153Q, insertion of a myc-tag), and two in loop E (H230G, insertion of a myc-tag). Fourty-seven baseline and 49 follow-up serum samples and six paired cerebrospinal fluid (CSF) baseline samples of 47 AQP4-IgG-positive Austrian NMOSD patients were then tested for their binding capability to AQP4-M1 and AQP4-M23 isoforms and these six extracellular loop mutants. RESULTS: Overall, we could identify two broad patterns of antibody recognition based on differential sensitivity to mutations in extracellular loop A. Pattern A was characterized by reduced binding to the two mutations in loop A, whereas pattern B had only partial or no reduced binding to these mutations. These two patterns were not associated with significant differences in demographic and clinical parameters or serum titers in this retrospective study. Interestingly, we found a change of AQP4-IgG epitope recognition pattern in seven of 20 NMOSD patients with available follow-up samples. Moreover, we found different binding patterns in five of six paired CSF versus serum samples, with a predominance of pattern A in CSF. CONCLUSIONS: Our study demonstrates that AQP4-IgG in sera of NMOSD patients show distinct patterns of antibody recognition. The clinical and diagnostic relevance of these findings have to be addressed in prospective studies. PMID- 27371175 TI - [Not Available]. PMID- 27371176 TI - [Not Available]. PMID- 27371177 TI - [Not Available]. PMID- 27371178 TI - [Not Available]. PMID- 27371179 TI - [Not Available]. PMID- 27371180 TI - [Not Available]. PMID- 27371181 TI - [Not Available]. PMID- 27371182 TI - [Not Available]. PMID- 27371183 TI - [Not Available]. PMID- 27371184 TI - Guidelines for Accurate and Transparent Health Estimates Reporting: the GATHER statement. AB - Measurements of health indicators are rarely available for every population and period of interest, and available data may not be comparable. The Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) define best reporting practices for studies that calculate health estimates for multiple populations (in time or space) using multiple information sources. Health estimates that fall within the scope of GATHER include all quantitative population-level estimates (including global, regional, national, or subnational estimates) of health indicators, including indicators of health status, incidence and prevalence of diseases, injuries, and disability and functioning; and indicators of health determinants, including health behaviours and health exposures. GATHER comprises a checklist of 18 items that are essential for best reporting practice. A more detailed explanation and elaboration document, describing the interpretation and rationale of each reporting item along with examples of good reporting, is available on the GATHER website. PMID- 27371186 TI - Total-body CT for initial diagnosis of severe trauma. PMID- 27371185 TI - Immediate total-body CT scanning versus conventional imaging and selective CT scanning in patients with severe trauma (REACT-2): a randomised controlled trial. AB - BACKGROUND: Published work suggests a survival benefit for patients with trauma who undergo total-body CT scanning during the initial trauma assessment; however, level 1 evidence is absent. We aimed to assess the effect of total-body CT scanning compared with the standard work-up on in-hospital mortality in patients with trauma. METHODS: We undertook an international, multicentre, randomised controlled trial at four hospitals in the Netherlands and one in Switzerland. Patients aged 18 years or older with trauma with compromised vital parameters, clinical suspicion of life-threatening injuries, or severe injury were randomly assigned (1:1) by ALEA randomisation to immediate total-body CT scanning or to a standard work-up with conventional imaging supplemented with selective CT scanning. Neither doctors nor patients were masked to treatment allocation. The primary endpoint was in-hospital mortality, analysed in the intention-to-treat population and in subgroups of patients with polytrauma and those with traumatic brain injury. The chi(2) test was used to assess differences in mortality. This trial is registered with ClinicalTrials.gov, number NCT01523626. FINDINGS: Between April 22, 2011, and Jan 1, 2014, 5475 patients were assessed for eligibility, 1403 of whom were randomly assigned: 702 to immediate total-body CT scanning and 701 to the standard work-up. 541 patients in the immediate total body CT scanning group and 542 in the standard work-up group were included in the primary analysis. In-hospital mortality did not differ between groups (total-body CT 86 [16%] of 541 vs standard work-up 85 [16%] of 542; p=0.92). In-hospital mortality also did not differ between groups in subgroup analyses in patients with polytrauma (total-body CT 81 [22%] of 362 vs standard work-up 82 [25%] of 331; p=0.46) and traumatic brain injury (68 [38%] of 178 vs 66 [44%] of 151; p=0.31). Three serious adverse events were reported in patients in the total-body CT group (1%), one in the standard work-up group (<1%), and one in a patient who was excluded after random allocation. All five patients died. INTERPRETATION: Diagnosing patients with an immediate total-body CT scan does not reduce in hospital mortality compared with the standard radiological work-up. Because of the increased radiation dose, future research should focus on the selection of patients who will benefit from immediate total-body CT. FUNDING: ZonMw, the Netherlands Organisation for Health Research and Development. PMID- 27371189 TI - [Not Available]. PMID- 27371187 TI - The rehabilitation of attention in patients with mild cognitive impairment and brain subcortical vascular changes using the Attention Process Training-II. The RehAtt Study: rationale, design and methodology. AB - Cerebral small vessel disease (SVD) may cause attentional and executive cognitive deficits. No drug is currently available to improve cognitive performance or to prevent dementia in SVD patients, and cognitive rehabilitation could be a promising approach. We aimed to investigate: (1) the effectiveness of the Attention Process Training-II program in the rehabilitation of patients with mild cognitive impairment (MCI) and SVD; (2) the impact of the induced cognitive improvement on functionality and quality of life; (3) the effect of training on brain activity at rest and the possibility of a training-induced plasticity effect. The RehAtt study is designed as a 3-year prospective, single-blinded, randomized clinical trial. Inclusion criteria were: (1) MCI defined according to Winblad et al. criteria; (2) evidence of impairment across attention neuropsychological tests; (3) evidence on MRI of moderate/severe white matter hyperintensities. All enrolled patients are evaluated at baseline, and after 6 and 12 months, according to an extensive clinical, functional, MRI and neuropsychological protocol. The baseline RehAtt cohort includes 44 patients (66 % males, mean +/- SD age and years of education 75.3 +/- 6.8 and 8.3 +/- 4.3, respectively). After baseline assessment, patients have been randomly assigned to 'attention training' or 'standard care'. Treatments and follow-up visits at 6 months are completed, while follow-up visits at 12 months are ongoing. This study is the first attempt to reduce attention deficits in patients affected by MCI with SVD. The results of this pilot experience will represent an essential background for designing larger multicenter, prospective, double-blinded, randomized and controlled clinical trials. TRIAL REGISTRATION: NCT02033850 (ClinicalTrials.gov Identifier). PMID- 27371190 TI - [Not Available]. PMID- 27371188 TI - Evaluation of carotid intima-media thickness in children with migraine: a marker of subclinical atherosclerosis. AB - Migraine is a commonly seen neurovascular disorder during childhood. Inflammation induced by the activation of cytokines and neuropeptides is implied in its pathophysiology. There is an association between inflammation and atherosclerosis in patients with migraine. In addition, there is a strong correlation between early atherosclerotic wall lesions and carotid intima-media thickness (CIMT). The study population consisted of 57 migraine patients aged 5-17 years, as well as 47 healthy children who served as the control group. Those migraine patients who were not receiving any medications at the interictal period were compared to healthy controls in terms of their measured lipid levels, thyroid function, vitamin B12 levels, serum iron levels, iron binding capacity, complete blood count, C-reactive protein (CRP) levels, and carotid intima-media thickness (CIMT) scores, which may comprise risk factors for atherosclerosis. When children in the migraine and control groups were compared in terms of those risk factors that are known to be related to vascular changes, no significant differences were found. However, a significant difference was detected in CIMT values (P < 0.05). Atherosclerosis commences in childhood, and there is a long period of time before the onset of ischemic symptoms occurs. In children with migraine, an evaluation of CIMT can be used as a non-invasive imaging modality to detect atherosclerosis, which develops in the context of chronic inflammation. In this way, measures to reduce morbidity and mortality, which may result from cardiovascular diseases, can be implemented. PMID- 27371192 TI - [Not Available]. PMID- 27371191 TI - [Not Available]. PMID- 27371193 TI - [Not Available]. PMID- 27371195 TI - [Not Available]. PMID- 27371194 TI - [Not Available]. PMID- 27371196 TI - [Not Available]. PMID- 27371197 TI - [Not Available]. PMID- 27371198 TI - [Not Available]. PMID- 27371199 TI - [Not Available]. PMID- 27371201 TI - [Not Available]. PMID- 27371200 TI - [Not Available]. PMID- 27371202 TI - [Not Available]. PMID- 27371203 TI - [Not Available]. PMID- 27371205 TI - [Not Available]. PMID- 27371204 TI - [Not Available]. PMID- 27371207 TI - [Not Available]. PMID- 27371206 TI - [Not Available]. PMID- 27371208 TI - [Not Available]. PMID- 27371209 TI - [Not Available]. PMID- 27371210 TI - [Not Available]. PMID- 27371211 TI - [Not Available]. PMID- 27371212 TI - [Not Available]. PMID- 27371213 TI - [Not Available]. PMID- 27371214 TI - [Not Available]. PMID- 27371215 TI - [Not Available]. PMID- 27371216 TI - [Not Available]. PMID- 27371217 TI - [Not Available]. PMID- 27371218 TI - [Not Available]. PMID- 27371219 TI - [Not Available]. PMID- 27371220 TI - [Not Available]. PMID- 27371221 TI - [Not Available]. PMID- 27371222 TI - Fipronil-induced genotoxicity and DNA damage in vivo: Protective effect of vitamin E. AB - Fipronil, an insecticide of the phenylpyrazole class has been classified as a carcinogen by United States Environmental Protection Agency, yet very limited information is available about its genotoxic effects. Adult male and female animals were gavaged with various doses of fipronil (2.5, 12.5, and 25 mg/kg body weight (bw)) to evaluate micronucleus test (mice), chromosome aberration (CA), and comet assay (rats), respectively. Cyclophosphamide (40 mg/kg bw; intraperitoneal) was used as positive control. Another group of animals were pretreated with vitamin E orally (400 mg/kg bw) for 5 days prior to administration of fipronil (12.5 mg/kg). Fipronil exposure in both male and female mice caused significant increase in the frequency of micronuclei (MN) in polychromatic erythrocytes. Similarly, structural CAs in bone marrow cells and DNA damage in the lymphocytes was found to be significantly higher in the male and female rats exposed to fipronil as compared to their respective controls. The average degree of protection (male and female animals combined together) shown by pretreatment of vitamin E against fipronil-induced genotoxicity was 63.28%: CAs; 47.91%: MN formation; and 74.70%: DNA damage. Findings of this study demonstrate genotoxic nature of fipronil regardless of gender effect and documents protective role of vitamin E. PMID- 27371223 TI - Corrigendum: Divergence of a conserved elongation factor and transcription regulation in budding and fission yeast. PMID- 27371225 TI - [Not Available]. PMID- 27371226 TI - [Not Available]. PMID- 27371224 TI - New insights into renal toxicity of the B-RAF inhibitor, vemurafenib, in patients with metastatic melanoma. AB - PURPOSE: Vemurafenib (VMF) is a B-RAF inhibitor used in the treatment of B-RAF V600-mutant metastatic melanomas. Reports of acute kidney injury (AKI) in patients treated with VMF are scarce. METHODS: To investigate the incidence and severity of AKI, we conducted a retrospective, observational, monocentric study in the Lyon Sud Hospital University, France, which included 74 patients with metastatic B-RAF-mutated melanomas treated with VMF, between June 2011 and August 2014. According to the Kidney Disease Improving Global Outcomes Guidelines, AKI is defined as an increase in serum creatinine concentration exceeding the baseline concentration by 1.5 fold. Serum creatinine was thus determined before treatment, on a monthly basis during treatment, and 3 months after treatment discontinuation. Patients were divided into two main groups: AKI-positive (AKI+) and AKI-negative (AKI-) and further subdivided into three groups according to AKI severity (stage 1, 2 or 3). To visualize the tissue damage caused by VMF, kidney biopsies were performed for two stage 1 AKI+ patients. RESULTS: Of the 74 patients, 30 (40.5 %) were AKI-, and of the 44 AKI+ patients (59.5 %), 29 (66 %) were diagnosed within the first three months of treatment. There were significantly more men in the AKI+ group: n = 33 (75 %) versus n = 12 (40 %) women, p = 0.004 with an odds ratio for developing AKI of 4.6 (95 % CI 1.48 14.23). Most AKI + cases were considered as stage 1 (n = 40; 91 %) and the remaining four (9 %) as stage 2 AKI. Kidney biopsies revealed interstitial fibrosis and acute focal tubular damage. However, renal failure was reversible in 80 % of patients within 3 months of VMF discontinuation. CONCLUSIONS: We observed frequent, reversible, moderately severe AKI with some histological evidence of tubular and interstitial damage in VMF-treated patients, suggesting that renal function should be carefully monitored in male patients, especially during the first 3 months. PMID- 27371228 TI - [Not Available]. PMID- 27371227 TI - [Not Available]. PMID- 27371229 TI - [Not Available]. PMID- 27371231 TI - [Not Available]. PMID- 27371230 TI - [Not Available]. PMID- 27371232 TI - [Not Available]. PMID- 27371233 TI - [Not Available]. PMID- 27371234 TI - [Not Available]. PMID- 27371235 TI - [Not Available]. PMID- 27371236 TI - [Not Available]. PMID- 27371237 TI - [Not Available]. PMID- 27371238 TI - [Not Available]. PMID- 27371239 TI - [Not Available]. PMID- 27371240 TI - [Not Available]. PMID- 27371241 TI - [Not Available]. PMID- 27371242 TI - [Not Available]. PMID- 27371243 TI - [Not Available]. PMID- 27371244 TI - [Not Available]. PMID- 27371245 TI - [Not Available]. PMID- 27371246 TI - [Not Available]. PMID- 27371247 TI - [Not Available]. PMID- 27371248 TI - [Not Available]. PMID- 27371249 TI - [Not Available]. PMID- 27371250 TI - [Not Available]. PMID- 27371251 TI - [Not Available]. PMID- 27371253 TI - [Not Available]. PMID- 27371252 TI - [Not Available]. PMID- 27371254 TI - [Not Available]. PMID- 27371256 TI - [Not Available]. PMID- 27371255 TI - [Not Available]. PMID- 27371257 TI - [Not Available]. PMID- 27371258 TI - [Not Available]. PMID- 27371259 TI - Integrated community case management and community-based health planning and services: a cross sectional study on the effectiveness of the national implementation for the treatment of malaria, diarrhoea and pneumonia. AB - BACKGROUND: Ghana has developed two main community-based strategies that aim to increase access to quality treatment for malaria, diarrhoea and pneumonia: the Home-based Care (HBC) and the Community-based Health Planning and Services (CHPS). The objective was to assess the effectiveness of HBC and CHPS on utilization, appropriate treatment given and users' satisfaction for the treatment of malaria, diarrhoea and pneumonia. METHODS: A household survey was conducted 2 and 8 years after implementation of HBC in the Volta and Northern Regions of Ghana, respectively. The study population was carers of children under five who had fever, diarrhoea and/or cough in the last 2 weeks prior to the interview. HBC and CHPS utilization were assessed based on treatment-seeking behaviour when the child was sick. Appropriate treatment was based on adherence to national guidelines and satisfaction was based on the perceptions of the carers after the treatment-seeking visit. RESULTS: HBC utilization was 17.3 and 1.0 % in the Volta and Northern Regions respectively, while CHPS utilization in the same regions was 11.8 and 31.3 %, with large variation among districts. Regarding appropriate treatment of uncomplicated malaria, 36.7 % (n = 17) and 19.4 % (n = 1) of malaria cases were treated with ACT under the HBC in the Volta and Northern Regions respectively, and 14.7 % (n = 7) and 7.4 % (n = 26) under the CHPS in the Volta and Northern Regions. Regarding diarrhoea, 7.6 % (n = 4) of the children diagnosed with diarrhoea received oral rehydration salts (ORS) or were referred under the HBC in the Volta Region and 22.1 % (n = 6) and 5.6 % (n = 8) under the CHPS in the Volta and Northern Regions. Regarding suspected pneumonia, CHPS in the Northern Region gave the most appropriate treatment with 33.0 % (n = 4) of suspected cases receiving amoxicillin. Users of CHPS in the Volta Region were the most satisfied (97.7 % were satisfied or very satisfied) when compared with those of the HBC and of the Northern Region. CONCLUSIONS: HBC showed greater utilization by children under-five years of age in the Volta Region while CHPS was more utilized in the Northern Region. Utilization of HBC contributed to prompt treatment of fever in the Volta Region. Appropriate treatment for the three diseases was low in the HBC and CHPS, in both regions. Users were generally satisfied with the CHPS and HBC services. PMID- 27371260 TI - Modeling Glucose Metabolism in the Kidney. AB - The mammalian kidney consumes a large amount of energy to support the reabsorptive work it needs to excrete metabolic wastes and to maintain homeostasis. Part of that energy is supplied via the metabolism of glucose. To gain insights into the transport and metabolic processes in the kidney, we have developed a detailed model of the renal medulla of the rat kidney. The model represents water and solute flows, transmural fluxes, and biochemical reactions in the luminal fluid of the nephrons and vessels. In particular, the model simulates the metabolism of oxygen and glucose. Using that model, we have identified parameters concerning glucose transport and basal metabolism that yield predicted blood glucose concentrations that are consistent with experimental measurements. The model predicts substantial axial gradients in blood glucose levels along various medullary structures. Furthermore, the model predicts that in the inner medulla, owing to the relatively limited blood flow and low tissue oxygen tension, anaerobic metabolism of glucose dominates. PMID- 27371262 TI - ERRATUM. PMID- 27371263 TI - ERRATUM. PMID- 27371261 TI - Plasma fatty acids, oxylipins, and risk of myocardial infarction: the Singapore Chinese Health Study. AB - We aimed to examine the prospective association between plasma FAs, oxylipins, and risk of acute myocardial infarction (AMI) in a Singapore Chinese population. A nested case-control study with 744 incident AMI cases and 744 matched controls aged 47-83 years was conducted within the Singapore Chinese Health Study. Nineteen plasma FAs and 12 oxylipins were quantified using MS. These were grouped into 12 FA clusters and 5 oxylipin clusters using hierarchical clustering, and their associations with AMI risk were assessed. Long-chain n-3 FAs [odds ratio (OR) = 0.67 per SD increase, 95% confidence interval (CI): 0.53-0.84, P < 0.001] and stearic acid (OR = 0.65, 95% CI: 0.44-0.97, P = 0.03) were inversely associated with AMI risk, whereas arachidonic acid (AA) was positively associated with AMI risk (OR = 1.25, 95% CI: 1.03-1.52, P = 0.02) in the multivariable model with adjustment for other FAs. Further adjustment for oxylipins did not substantially change these associations. An inverse association was observed between AA-derived oxylipin, thromboxane (TX)B2, and AMI risk (OR = 0.81, 95% CI: 0.71-0.93, P = 0.003). Circulating long-chain n-3 FAs and stearic acid were associated with a lower and AA was associated with a higher AMI risk in this Chinese population. The association between the oxylipin TXB2 and AMI requires further research. PMID- 27371264 TI - Evaluation of Vaccines Injection Order on Pain Score of Intramuscular Injection of Diphtheria, Whole Cell Pertussis and Tetanus Vaccine. AB - OBJECTIVE: To determine, whether or not intramuscular injection of diphtheria, pertussis and tetanus (DwPT) vaccine should be given first and subcutaneous injection of measles, mumps and rubella (MMR) thereafter or vice versa and can this cause less pain of DwPT vaccine injection. METHODS: In a randomized parallel group clinical trial, seventy 18-mo-old healthy children who were referred for routine vaccination to Akbari Health Care Center, Yazd, Iran from September 2014 through March 2015 were randomly allocated to two groups to receive DwPT and then MMR vaccines or MMR first, and then DwPT. Primary outcomes included pain score during DwPT injection, pain score during MMR injection, overall pain score of vaccination and obtaining a pain score of less than three during DwPT injection. Pain scores were assessed based on Modified Behavioral Pain Scale. Secondary outcome was crying duration during DwPT injection. RESULTS: Thirty seven girls and 33 boys were evaluated in two groups. Pain scores of DwPT and MMR injections, the frequency of pain score obtained to be less than three during DwPT injection and the crying duration were not different in both groups. But, overall pain score of vaccination was lower when subcutaneous injection of MMR vaccine was given before intramuscular injection of DwPT vaccine. (14.23 +/- 1.35 vs. 15.61 +/- 2.65; P = 0.04). CONCLUSIONS: Overall pain score of vaccination in multiple vaccine injection at the same visit might be reduced if subcutaneous vaccine is injected before intramuscular one. PMID- 27371266 TI - [Not Available]. PMID- 27371267 TI - [Not Available]. PMID- 27371265 TI - Role of ERCP in Patients With Idiopathic Recurrent Acute Pancreatitis. AB - OPINION STATEMENT: Recurrent acute pancreatitis (RAP) is defined based on the occurrence of two or more episodes of acute pancreatitis. RAP is differentiated from chronic pancreatitis based on the presence of a normal morphological appearance of the pancreas between episodes. RAP can be due to a variety of etiologies including common bile duct stones or sludge, sphincter of Oddi dysfunction (SOD), pancreas divisum (PD), anomalous pancreaticobiliary junction, genetic mutations, and alcohol related. In approximately 30 % of patients, the etiology of RAP is unclear and the term "idiopathic" is used. Endoscopic retrograde cholangiopancreatography (ERCP) can be utilized in both the diagnosis and the initial management of RAP, but it has known limitations and risks. Since gallbladder sludge and SOD account for most cases with RAP, cholecystectomy and, eventually, endoscopic biliary and/or pancreatic sphincterotomy are performed as a part of management. In patients with PD-associated RAP, data from uncontrolled and primarily retrospective studies point toward a benefit from minor papillary endoscopic intervention. However, given the lack of quality data from prospective randomized controlled trials (RCTs), endoscopic management in such patients remains an individualized decision, and RCTs are needed to ascertain its true long-term benefit. Future studies to investigate the role of endoscopic therapy in preventing progression to chronic pancreatitis are needed. PMID- 27371268 TI - [Not Available]. PMID- 27371269 TI - [Not Available]. PMID- 27371270 TI - [Not Available]. PMID- 27371272 TI - [Not Available]. PMID- 27371271 TI - [Not Available]. PMID- 27371273 TI - [Not Available]. PMID- 27371274 TI - [Not Available]. PMID- 27371275 TI - [Not Available]. PMID- 27371276 TI - [Not Available]. PMID- 27371277 TI - [Not Available]. PMID- 27371278 TI - [Not Available]. PMID- 27371279 TI - [Not Available]. PMID- 27371280 TI - [Not Available]. PMID- 27371281 TI - [Not Available]. PMID- 27371283 TI - [Not Available]. PMID- 27371282 TI - [Not Available]. PMID- 27371284 TI - [Not Available]. PMID- 27371285 TI - [Not Available]. PMID- 27371286 TI - [Not Available]. PMID- 27371287 TI - [Not Available]. PMID- 27371288 TI - [Not Available]. PMID- 27371289 TI - [Not Available]. PMID- 27371290 TI - Does meniscus removal affect ACL-deficient knee laxity? An in vivo study. AB - PURPOSE: The purpose of the present study was to determine, in vivo, the effect of different types of meniscectomy on an ACL-deficient knee. METHODS: Using a computer-assisted navigation system, 56 consecutive patients (45 men and 11 women) were subjected to a biomechanical testing with Lachman test (AP30), drawer test (AP90), internal/external rotation test, varus/valgus rotation test and pivot-shift test. The patients were divided into three groups according to the status of the medial meniscus. Group BH, 8 patients with bucket-handle tear of medial meniscus underwent a subtotal meniscectomy; Group PHB, 19 patients with posterior horn body of medial meniscus tear underwent a partial meniscectomy; and Group CG with isolated ACL rupture, as a control group, with 29 patients. RESULTS: A significant difference in anterior tibial translation was seen at 30 grades and in 90 grades between BH and PHB groups compared to the CG. In response to pivot-shift test, no significant differences in terms of AREA and POSTERIOR ACC were found among the three groups (n.s). Concerning the anterior displacement of the pivot shift a statistically significant differences among the three tested groups was found. CONCLUSION: The present study shows that meniscal defects significantly affect the kinematics of an ACL-deficient knee in terms of anterior tibial translation under static and dynamic testing. PMID- 27371291 TI - Anatomic single-bundle anterior cruciate ligament reconstruction improves walking economy: hamstrings tendon versus patellar tendon grafts. AB - PURPOSE: Anterior cruciate ligament (ACL) injury is associated with a pathologic gait pattern and increased energy cost during locomotion. ACL reconstruction could improve the gait pattern. Hamstrings tendon (HAM) and bone-patellar tendon bone (BPTB) grafts are usually used for reconstruction. The aim of this study was to compare the efficacy of anatomic ACL reconstruction with HAM and BPTB grafts on improving and normalizing the energy cost and physiologic reserves during flat, uphill, and downhill walking. METHODS: Twenty male subjects with unilateral ACL injuries were randomly assigned to ACL reconstruction with a HAM (n = 10) or BPTB (n = 10) graft. Ten matched controls were also enrolled. All participants performed three 8-min walking tasks at 0, +10, and -10 % gradients before and 9 months after surgery. Energy cost (oxygen consumption, VO2), heart rate (HR), and ventilation (VE) were measured. Lysholm/IKDC scores were recorded. RESULTS: Pre operatively, VO2, HR, and VE were higher in the HAM and BPTB groups than in controls during walking at 0, +10, and -10 % gradients (p < 0.001-0.01). Post operatively, both HAM and BPTB groups showed reduced VO2, HR, and VE during the three walking tasks (p < 0.001-0.01). Although the post-operative VO2 in both surgical groups reached 90-95 % of the normative (control) value during walking, it remained elevated against the value observed in controls (p < 0.001-0.01). The HAM and BPTB groups showed no differences in post-surgical VO2 or HR during walking at all three gradients. CONCLUSION: Anatomic ACL reconstruction with either HAM or BPTB graft resulted in similar short-term improvements in energy cost and nearly normalized locomotion economy and cardiorespiratory reserves during flat, uphill, and downhill walking. The improved locomotion economy is an additional benefit of anatomic ACL reconstruction, irrespective of the type of graft used, that the orthopaedic surgeons should consider. LEVEL OF EVIDENCE: II. PMID- 27371292 TI - Early weight bearing versus delayed weight bearing in medial opening wedge high tibial osteotomy: a randomized controlled trial. AB - PURPOSE: The need for a period of non-weight bearing after medial opening wedge high tibial osteotomy remains controversial. It is hypothesized that immediate weight bearing after medial opening wedge high tibial osteotomy would have no difference in functional scores at one year compared to delayed weight bearing. METHODS: Fifty patients, median age 54 years (range 40-65), with medial compartment osteoarthritis, underwent a medial opening wedge high tibial osteotomy utilizing a locking plate without bone grafting. Patients were randomized into an Immediate or a Delayed (2 months) weight bearing group. All patients were assessed at one-year follow-up and the two groups compared. The primary outcome measure was the IKS score. Secondary outcome measures included the IKDC score, the VAS pain score and rate of complications. RESULTS: The functional scores significantly improved in both groups. The IKS score increased from 142 +/- 31 to 171 +/- 26 in the Immediate group (p < 0.001) and from 148 +/- 22 to 178 +/- 23 in the Delayed group (p < 0.001). The IKDC score increased from 49 +/- 17 pre-operatively to 68 +/- 14 one-year post-operatively in the Immediate group (p < 0.0001) and from 44 +/- 16 to 69 +/- 19 in the Delayed group (p < 0.001). The average VAS for pain 2 months after surgery was 3 +/- 3 in the Immediate group and 3 +/- 2 in the Delayed (n.s.). There was no significant difference between the two groups in any of the outcome measures. The mean mechanical femorotibial angle changed from 6 degrees of varus (0 degrees -15 degrees of varus, SD = 3 degrees ) to 4 degrees of valgus (5 degrees -11 degrees of valgus, SD = 3 degrees ) in the Immediate group and from 5 degrees of varus (0 degrees -10 degrees of varus, SD = 3 degrees ) to 3 degrees of valgus (2 degrees of varus to 8 degrees of valgus, SD = 3 degrees ) in the Delayed group. No difference was seen between groups, and no loss of correction was observed in any patient. Two cases of non-union occurred, one in each group. One infection and one deep vein thrombosis occurred in the Immediate group. CONCLUSION: Immediate weight bearing after medial opening wedge high tibial osteotomy had no effect on functional scores at 1 year follow-up and did not significantly increase the complication rate. Immediate weight bearing after medial opening wedge high tibial osteotomy appears to be safe and can allow some patients a quicker return to activities of daily living and a decreased convalescence period. LEVEL OF EVIDENCE: II. PMID- 27371293 TI - RN-BS Students' Reports of Their Self-Care and Health-Promotion Practices in a Holistic Nursing Course. AB - PURPOSE: This study explored RN-BS students' self-care and health-promotion (SCHP) practices in a semester-long holistic nursing course with emphasis on the utility of self-reflection through journal writing. DESIGN: A qualitative single case study blended in practical action research. METHOD: Fifteen RN-BS students enrolled in the holistic nursing course completed (a) three reflective journal entries (beginning, midterm, and conclusion); (b) two IHWA-short form surveys (beginning and conclusion); and (c) one demographic form (beginning) of the course. FINDINGS: Three reflective journals indicated that students' understanding of their SCHP practices progressed from novice, to advanced, and finally to competent from the beginning, middle, and at the conclusion of the course. Four findings emerged in relation to reports of their SCHP practices: (a) new awareness of self, (b) application of SCHP practices knowledge, (c) role modeling, and (d) dedication to SCHP practices beyond the semester. Four findings emerged in relation to participation in the reflective journaling about reports of their SCHP practices: (a) self-discovery, (b) retrospective self-evaluation, (c) useful intervention for SCHP, and (d) beneficial learning tool in academic environment. CONCLUSIONS: Reflective journaling enhanced students' SCHP practices and was recognized as useful instructional strategy to improve learning in the classroom. PMID- 27371294 TI - [Not Available]. PMID- 27371295 TI - [Not Available]. PMID- 27371297 TI - [Not Available]. PMID- 27371296 TI - [Not Available]. PMID- 27371298 TI - [Not Available]. PMID- 27371299 TI - [Not Available]. PMID- 27371300 TI - [Not Available]. PMID- 27371301 TI - [Not Available]. PMID- 27371302 TI - [Not Available]. PMID- 27371303 TI - [Not Available]. PMID- 27371304 TI - [Not Available]. PMID- 27371305 TI - [Not Available]. PMID- 27371306 TI - [Not Available]. PMID- 27371307 TI - [Not Available]. PMID- 27371308 TI - [Not Available]. PMID- 27371309 TI - [Not Available]. PMID- 27371311 TI - [Not Available]. PMID- 27371310 TI - [Not Available]. PMID- 27371312 TI - [Not Available]. PMID- 27371313 TI - [Not Available]. PMID- 27371314 TI - [Not Available]. PMID- 27371315 TI - [Not Available]. PMID- 27371316 TI - [Not Available]. PMID- 27371318 TI - [Not Available]. PMID- 27371317 TI - [Not Available]. PMID- 27371319 TI - [Not Available]. PMID- 27371321 TI - Canada's new assisted dying law faces legal challenge. PMID- 27371320 TI - Cdk2 catalytic activity is essential for meiotic cell division in vivo. AB - Cyclin-dependent kinases (Cdks) control the eukaryotic cell cycle by phosphorylating serine and threonine residues in key regulatory proteins, but some Cdk family members may exert kinase-independent functions that cannot easily be assessed using gene knockout approaches. While Cdk2-deficient mice display near-normal mitotic cell proliferation due to the compensatory activities of Cdk1 and Cdk4, they are unable to undergo meiotic generation of gametes and are consequently sterile. To investigate whether Cdk2 regulates meiosis via protein phosphorylation or by alternative kinase-independent mechanisms, we generated two different knockin mouse strains in which Cdk2 point mutations ablated enzyme activity without altering protein expression levels. Mice homozygous for the mutations Cdk2(D145N/D145N) or Cdk2(T160A/T160A) expressed only 'kinase-dead' variants of Cdk2 under the control of the endogenous promoter, and despite exhibiting normal expression of cell cycle regulatory proteins and complexes, both mutations rendered mice sterile. Mouse cells that expressed only 'kinase dead' variants of Cdk2 displayed normal mitotic cell cycle progression and proliferation both in vitro and in vivo, indicating that loss of Cdk2 kinase activity exerted little effect on this mode of cell division. In contrast, the reproductive organs of Cdk2 mutant mice exhibited abnormal morphology and impaired function associated with defective meiotic cell division and inability to produce gametes. Cdk2 mutant animals were therefore comparable to gene knockout mice, which completely lack the Cdk2 protein. Together, our data indicate that the essential meiotic functions of Cdk2 depend on its kinase activity, without which the generation of haploid cells is disrupted, resulting in sterility of otherwise healthy animals. PMID- 27371322 TI - [Not Available]. PMID- 27371323 TI - [Not Available]. PMID- 27371325 TI - [Not Available]. PMID- 27371324 TI - [Not Available]. PMID- 27371326 TI - [Not Available]. PMID- 27371327 TI - [Not Available]. PMID- 27371329 TI - [Not Available]. PMID- 27371328 TI - [Not Available]. PMID- 27371331 TI - On the origin of ear clicks during deglutition or pressure equalization. AB - To explore the origin of clicking sounds in the ear during deglutition or other pharyngeal movements, which are interpreted differently in the literature. Experimental study at a tertiary referral centre. Acoustic phenomena during a forced opening test of the Eustachian tube (ET) were studied in a temporal bone model. Additionally, in vivo experiments were carried out in healthy volunteers for ruling out movements of the ossicular chain or the drumhead as potential causes of clicks. Thus, acoustic recordings were performed parallel to stapedius or tensor reflex measurements or pneumatic video endoscopies of the tympanic membrane. Obviously the acoustic signals (clicks) appear when the tube opens, which could be visualized and acoustically recorded during forced opening tests in temporal bone experiments. Middle ear muscle contractions with movements of the tympanic membrane did not cause any click events. Together with the results of a previous paper (9) we interpret the clicks as disruptions of fluid or mucus films covering the mucosa during the ET opening. The final goal of our studies is to use such clicks as indicators of ET openings in a new tube function test, which has to be elaborated. PMID- 27371330 TI - Predicting postoperative fever and bacterial colonization on packing material following endoscopic endonasal surgery. AB - Postoperative fever following endoscopic endonasal surgery is a rare occurrence of concern to surgeons. To elucidate preoperative and operative predictors of postoperative fever, we analyzed the characteristics of patients and their perioperative background in association with postoperative fever. A retrospective review of 371 patients who had undergone endoscopic endonasal surgery was conducted. Predictors, including intake of antibiotics, steroids, history of asthma, preoperative nasal bacterial culture, duration of operation, duration of packing and intraoperative intravenous antibiotics on the occurrence of postoperative fever, and bacterial colonization on the packing material, were analyzed retrospectively. Fever (>=38 degrees C) occurred in 63 (17 %) patients. Most incidences of fever occurred on postoperative day one. In majority of these cases, the fever subsided after removal of the packing material without further antibiotic administration. However, one patient who experienced persistent fever after the removal of packing material developed meningitis. History of asthma, prolonged operation time (>=108 min), and intravenous cefazolin administration instead of cefmetazole were associated with postoperative fever. Odds ratios (ORs) for each were 2.3, 4.6, and 2.0, respectively. Positive preoperative bacterial colonization was associated with postoperative bacterial colonization on the packing material (OR 2.3). Postoperative fever subsided in most patients after removal of the packing material. When this postoperative fever persists, its underlying cause should be examined. PMID- 27371332 TI - Reliability and comparison of gain values with occurrence of saccades in the EyeSeeCam video head impulse test (vHIT). AB - : The vHIT (video head impulse test) investigates the vestibular function in two ways: a VOR (vestibulo-ocular reflex) gain value and a head impulse diagram. From the diagram covert and overt saccades can be detected. Evaluation of the vestibular function based on vHIT depends on both parameters. There is a lack of knowledge regarding the reliability of the two parameters. The objective was to investigate the reliability of vHIT by comparing gain values between examiners on the same subjects, and to see how differences affected the occurrence of saccades. SUBJECTS: 25 subjects who had undergone cochlear implant (CI) surgery. Subjects were tested using the vHIT by two of four different examiners. Two judges interpreted the occurrence of saccades in the diagram. MAIN OUTCOME MEASURES: VOR gain values and the occurrence of saccades in the diagram. Differences in gain values between examiners varied from 0.2 to 0.58 with an average of 0.14 (95 % CI 0.12-0.16) on the right ear and 0.17 (95 % CI 0.15-0.19) on the left ear. Occurrences of saccades in the same patient were reproduced in 93 % of the cases by all examiners. Kappa's coefficient on the occurrence of saccades was 0.83. Interclass correlation coefficient (ICC) of the gain values between examiners ranged from 0.62 to 0.70. Differences in gain values amongst examiners did not seem to affect the occurrence of saccades in the same patient. The occurrence of saccades, therefore, seems to be more reliable than the gain value in the evaluation of the vestibular function. Interpretation of vHIT results should, therefore, first depend on the occurrence of saccades and second on the gain value. PMID- 27371334 TI - [Not Available]. PMID- 27371335 TI - [Not Available]. PMID- 27371333 TI - Minimally invasive resection of extradural dumbbell tumors of thoracic spine: surgical techniques and literature review. AB - PURPOSE: Dumbbell-shaped thoracic tumors represent a distinct type of tumor and involve in both the spinal canal and the posterior thoracic cavity. Successful treatment for the tumors depends on gross total resection (GTR) via an open laminectomy and facetectomy or transthoracic transpleural approach. In this case series, we report our experiments with minimally invasive method for the removal of extradural dumbbell thoracic tumor and present related literature review. METHODS: We retrospectively reviewed two patients with dumbbell-shaped thoracic tumors who underwent minimally invasive resection and unilateral transforaminal thoracic intervertebral fusion (TTIF) through unilateral paraspinal muscle approachwith a spotlight expandable tubular retractor. Clinical data, tumor characteristics, and outcomes were analyzed. RESULTS: Two patients underwent successful minimally invasive treatment of their spinal neoplasms. There were no procedure-related complications. The efficacy in terms of neurological recovery, pain improvement and operative variables (length of incision, operative duration, blood loss, and hospital stay) was better when compared with prior published studies. Postoperative CT image demonstrated complete resection of dumbbell tumor in the patients. The solid fusion was obtained after 3 months follow-up and there was no failure of internal fixation. CONCLUSION: If the medial border of intracanal component of extradural dumbbell tumor is near the midline of canal and the pedicles of adjacent vertebrae to tumor are intact, minimally invasive resection of tumor through unilateral paraspinal muscle approach combined with unilateral TTIF is good choice. PMID- 27371336 TI - Fatty acid composition of spermatozoa is associated with BMI and with semen quality. AB - High body mass index (BMI) is negatively associated with semen quality. In addition, the composition of fatty acids of spermatozoa has been shown to be important for their function. The aim of the study was to examine the association between BMI and the composition of spermatozoa fatty acids in men spanning a broad BMI range. We also analysed the relation between fatty acid composition of spermatozoa and semen characteristics, and the relationship between serum fatty acids and spermatozoa fatty acids. One hundred forty-four men with unknown fertility status were recruited from the general population, from couples with identified female infertility and from morbid obesity centres. Standard semen analysis (WHO) and sperm DNA integrity (DFI) analysis were performed. Fatty acid compositions were assessed by gas chromatography. When adjusted for possible confounders, BMI was negatively associated with levels of sperm docosahexaenoic acid (DHA) (p < 0.001) and palmitic acid (p < 0.001). The amount of sperm DHA correlated positively with total sperm count (r = 0.482), sperm concentration (r = 0.469), sperm vitality (r = 0.354), progressive sperm motility (r = 0.431) and normal sperm morphology (r = 0.265). A negative association was seen between DHA levels and DNA fragmentation index (r = -0.247). Levels of spermatozoa palmitic acid correlated positively with total sperm count (r = 0.227), while levels of linoleic acid correlated negatively (r = -0.254). When adjusted for possible confounders, only the levels of arachidonic acid showed positive correlation between spermatozoa and serum phospholipids (r = 0.262). Changes in the fatty acid composition of spermatozoa could be one of the mechanisms underlying the negative association between BMI and semen quality. The relationship between fatty acids of spermatozoa and serum phospholipids was minor, which indicates that BMI affects fatty acid composition of spermatozoa through regulation of fatty acid metabolism in the testis. The role of dietary intake of fatty acids on the spermatozoa fatty acid composition remains to be elucidated. PMID- 27371337 TI - RETRACTED ARTICLE: Complex Effect of RNA Spliceosome Inhibition on Amyloid Precursor Protein Expression. PMID- 27371338 TI - Protective effects of PF-4708671 against N-methyl-d-aspartic acid-induced retinal damage in rats. AB - We previously demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), protects against N-methyl-d-aspartic acid (NMDA)-induced retinal damage in rats. Rapamycin inhibits mTOR activity, thereby preventing the phosphorylation of ribosomal protein S6, which is a downstream target of S6 kinase. Therefore, we aimed to determine whether PF-4708671, an inhibitor of S6 kinase, protects against NMDA-induced retinal injury. Intravitreal injection of NMDA (200 nmol/eye) caused cell loss in the ganglion cell layer and neuroinflammatory responses, such as an increase in the number of CD45-positive leukocytes and Iba1-positive microglia. Surprisingly, simultaneous injection of PF-4708671 (50 nmol/eye) with NMDA significantly attenuated these responses without affecting phosphorylated S6 levels. These results suggest that PF-4708671 and rapamycin likely protect against NMDA-induced retinal damage via distinct pathways. The neuroprotective effect of PF-4708671 is unlikely to be associated with inhibition of the S6 kinase, even though PF-4708671 is reported to be a S6 kinase inhibitor. PMID- 27371339 TI - Changing prevalence and treatment outcomes of patients with p16 human papillomavirus related oropharyngeal squamous cell carcinoma in New Zealand. AB - There has, to our knowledge, been no previous report of changes in the prevalence and outcomes of treatment of HPV-positive (+) oropharyngeal squamous cell carcinoma (SCC) in New Zealand. We identified all affected patients in the greater Wellington region between 1 January 1994 and 30 November 2014 from the New Zealand Cancer Registry. Their personal details, characteristics of their tumours, treatment, complications, and outcomes were collected retrospectively from their casenotes and the New Zealand Death Registry, followed by p16 immunohistochemical staining. Of the 161 patients included, 131 (81%) were men. p16 immunohistochemical staining was done routinely in 13 patients during investigations, and retrospectively for 135 patients. The proportion of p16+ oropharyngeal SCC increased from 24% during 1994-1999, to 76% during 2009-2014 (p<0.001). Oropharyngeal SCC among Europeans was more likely to be p16+ than in non-Europeans (67% compared with 44%, p=0.036). Patients with p16+ disease were younger (mean (SD) 56 (10) compared with 66 (9) years, p<0.01) with fewer coexisting conditions (mean (SD) Charlson Comorbidity Index: 2.45 (0.82) compared with 2.92 (1.16), p=0.01), and less likely to have smoked (57/81(70%) compared with 38/42 (91%) p=0.035), or misused alcohol (12/81 (15%) compared with 14/42 (31%), p=0.042), or both. They were also more likely to have poorly differentiated tumours (30/52 (58%) compared with 9/34 (26%), p=0.019) with nodal metastases (74/85 (87%) compared with 17/30 (57%), p=0.001). Overall 5-year all cause survival was more favourable for patients with p16+ disease (65/86 (76%) compared with 15/49 (31%), p=0.000). Interestingly, all-cause age at death was younger in p16+ patients (62 (11.1) compared with 71 (11.2) years, p=0.001). The prevalence of p16+ oropharyngeal SCC had tripled in this population between 1994 and 2014, and affected patients have distinct characteristics and outcomes of treatment. PMID- 27371340 TI - Intraosseous generation of heat during guided surgical drilling: an ex vivo study of the effect of the temperature of the irrigating fluid. AB - We measured the rise in the intraosseous temperature caused by freehand drilling or drilling through a surgical guide, by comparing different temperatures of irrigation fluid (10 degrees C, 15 degrees C, and 20 degrees C), for every step of the drilling sequence (diameters 2.0, 2.5, 3.0, and 3.5mm) and using a constant drilling speed of 1200rpm. The axial load was controlled at 2.0kg. Bovine ribs were used as test models. In the guided group we used 3-dimensional printed surgical guides and temperature was measured with a thermocouple. The significance of differences was assessed with the Kruskal-Wallis analysis of variance. Guided drilling with 10 degrees C irrigation yielded a significantly lower increment in temperature than the 20 degrees C-guided group. When compared with the 20 degrees C freehand group, the reduction in temperature in the 10 degrees C guided group was significantly more pronounced at all diameters except 3.5mm. Finally, when the 10 degrees C-guided group was compared with the 15 degrees C groups, the temperature rise was significantly less at 2.5 and 3.0mm than with the guided technique, and at 3.0mm compared with the freehand technique. We suggest that the use of 10 degrees C pre-cooled irrigation fluid is superior to warmer fluid for keeping temperature down, and this reduces the difference between guided and freehand drilling. PMID- 27371341 TI - Comparison of insulin lispro mix 25 with insulin lispro mix 50 as insulin starter in Chinese patients with type 2 diabetes mellitus (CLASSIFY study): Subgroup analysis of a Phase 4 open-label randomized trial. AB - BACKGROUND: Premixed insulins are recommended starter insulins in Chinese patients after oral antihyperglycemic medication (OAM) failure. In the present study, we compared the efficacy and safety of insulin lispro mix 25 (LM25) twice daily (b.i.d.) and insulin lispro mix 50 (LM50) b.i.d. as a starter insulin regimen in Chinese patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with OAMs. METHODS: The primary efficacy outcome in the present open-label parallel randomized clinical trial was change in HbA1c from baseline to 26 weeks. Patients were randomized in a ratio of 1: 1 to LM25 (n = 80) or LM50 (n = 76). A mixed-effects model with repeated measures was used to analyze continuous variables. The Cochran-Mantel-Haenszel test with stratification factor was used to analyze categorical variables. RESULTS: At the end of the study, LM50 was more efficacious than LM25 in reducing mean HbA1c levels (least-squares [LS] mean difference 0.48; 95 % confidence interval [CI] 0.22, 0.74; P < 0.001). More subjects in the LM50 than LM25 group achieved HbA1c targets of <7.0 % (72.4 % vs 45.0 %; P = 0.001) or <=6.5 % (52.6 % vs 20.0 %; P < 0.001). Furthermore, LM50 was more effective than LM25 at reducing HbA1c in patients with baseline HbA1c, blood glucose excursion, and postprandial glucose greater than or equal to median levels (P <= 0.001). The rate and incidence of hypoglycemic episodes and increase in weight at the end of the study were similar between treatment groups. CONCLUSIONS: In Chinese patients with T2DM, LM50 was more efficacious than LM25 as a starter insulin. PMID- 27371342 TI - Association of COL1A1 polymorphism with subchondral bone degeneration of the temporomandibular joint. AB - The G/T polymorphism of the COL1A1 gene exhibits a clinically significant influence on bone remodelling, leading to a predisposition to degenerative diseases. The enhancement of bone turnover and further loss of bone mass are thought to be the primary pathological changes in the early degenerative course of temporomandibular joint osteoarthritis (TMJ OA), with the appearance of low density lesions. Thus, it was hypothesized that this polymorphism may also affect this type of bone lesion in TMJ OA. A total of 130 TMJ OA patients with low density lesions (cortical bone erosion, condylar head resorption, cyst-like lesion) and 186 healthy individuals were recruited. DNA samples were extracted from buccal mucosa swabs; genotyping was performed by high-resolution melting assay. The distribution of genotypes in these groups was compared using a multivariate logistic regression model. No significant differences in the distributions of TT and TG genotypes were observed between the groups (P>0.05). Significance was detected for GG homozygous carriers (P=0.043); this genotype might be a risk factor for this type of low-density lesion (odds ratio 1.643, 95% confidence interval 1.016-2.658). This study indicates that the GG genotype might be a risk factor for low-density lesions in the TMJ. PMID- 27371343 TI - Neonatal outcomes according to different therapies for gestational diabetes mellitus. AB - OBJECTIVES: To compare different neonatal outcomes according to the different types of treatments used in the management of gestational diabetes mellitus. METHODS: This was a retrospective cohort study. The study population comprised pregnant women with gestational diabetes treated at a public maternity hospital from July 2010 to August 2014. The study included women aged at least 18 years, with a singleton pregnancy, who met the criteria for gestational diabetes mellitus. Blood glucose levels, fetal abdominal circumference, body mass index and gestational age were considered for treatment decision-making. The evaluated neonatal outcomes were: type of delivery, prematurity, weight in relation to gestational age, Apgar at 1 and 5min, and need for intensive care unit admission. RESULTS: The sample consisted of 705 pregnant women. The neonatal outcomes were analyzed based on the treatment received. Women treated with metformin were less likely to have children who were small for gestational age (95% CI: 0.09-0.66) and more likely to have a newborn adequate for gestational age (95% CI: 1.12 3.94). Those women treated with insulin had a lower chance of having a preterm child (95% CI: 0.02-0.78). The combined treatment with insulin and metformin resulted in higher chance for a neonate to be born large for gestational age (95% CI: 1.14-11.15) and lower chance to be born preterm (95% CI: 0.01-0.71). The type of treatment did not affect the mode of delivery, Apgar score, and intensive care unit admission. CONCLUSIONS: The pediatrician in the delivery room can expect different outcomes for diabetic mothers based on the treatment received. PMID- 27371344 TI - Mitochondrial neuropathy affects peripheral and cranial nerves and is primary or secondary or both. PMID- 27371345 TI - Tacrolimus-associated hemolytic uremic syndrome in a pediatric heart transplant recipient. AB - HUS is a well-known entity primarily associated with bacterial infection and is characterized by a classic triad of anemia, thrombocytopenia, and kidney injury. Its atypical form has been associated with calcineurin inhibitors and has been extensively discussed in renal transplantation. We present a case of tacrolimus associated HUS in a pediatric heart transplant recipient, which we believe to be previously unreported in the literature. PMID- 27371346 TI - Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry for the identification of Neisseria gonorrhoeae. AB - Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) was compared with the API NH biochemical method for the identification of Neisseria gonorrhoeae in routine clinical samples. A retrospective review of laboratory records for 1090 isolates for which both biochemical and MALDI-TOF MS identifications were available was performed. Cases of discrepant results were examined in detail for evidence supportive of a particular organism identification. Of 1090 isolates, 1082 were identified as N. gonorrhoeae by API NH. MALDI-TOF MS successfully identified 984 (91%) of these after one analysis, rising to 1081 (99.9%) after two analyses, with a positive predictive value of 99.3%. For those isolates requiring a repeat analysis, failure to generate an identifiable proteomic signature was the reason in 76% of cases, with alternative initial identifications accounting for the remaining 24%. MALDI-TOF MS identified eight isolates as N. gonorrhoeae that were not identified as such by API NH-examination of these discrepant results suggested that the MALDI-TOF MS identification may be the more reliable. MALDI-TOF MS is at least as accurate and reliable a method of identifying N. gonorrhoeae as API NH. We propose that MALDI-TOF MS could potentially be used as a single method for N. gonorrhoeae identification in routine cases by laboratories with access to this technology. PMID- 27371347 TI - Biotypes analysis of Corynebacterium glutamicum growing in dicarboxylic acids demonstrates the existence of industrially-relevant intra-species variations. AB - Production enhancement of industrial microbial products or strains has been traditionally tackled by mutagenesis with chemical methods, irradiation or genetic manipulation. However, the final yield increase must go hand in hand with the resistance increasing against the usual inherent toxicity of the final products. Few studies have been carried out on resistance improvement and even fewer on the initial selection of naturally-generated biotypes, which could decrease the artificial mutagenesis. This fact is vital in the case of GRAS microorganisms as Corynebacterium glutamicum involved in food, feed and cosmetics production.The characteristic wide diversity and plasticity in terms of their genetic material of Actinobacteria eases the biotypes generation. Thus, differences in morphology, glutamate and lysine production and growth in media supplemented with dicarboxylic acids were analysed in four biotypes of C. glutamicum ATCC 13032. A 2D-DIGE analysis of these biotypes growing with itaconic acid allowed us to define their differences. Thus, an optimized central metabolism and better protection against the generated stress conditions present the CgL biotype as a suitable platform for production of itaconic acid, which is used as a building block (e.g.: acrylic plastic). This analysis highlights the preliminary biotypes screening as a way to reach optimal industrial productions. PMID- 27371348 TI - Proteomic investigation of the prefrontal cortex in the rat clomipramine model of depression. AB - : Neonatal rodents chronically treated with the tricyclic antidepressant clomipramine show depression-like behavior, which persists throughout adulthood. Therefore, this animal model is suitable to investigate the pathomechanism of depression, which is still largely unknown at the molecular level beyond monoaminergic dysfunctions. Here, we describe protein level changes in the prefrontal cortex of neonatally clomipramine-treated adult rats correlating with behavioral abnormalities. Clomipramine was administered to rat pups twice daily between postnatal days 8-21, while controls received saline injections. Behavioral tests were performed on 3months old rats. The proteomic study was conducted using two-dimensional differential gel electrophoresis. We have identified 32 proteins by mass spectrometry analysis of the significantly altered protein spots. The changed proteins are related to several biological functions, such as inflammation, transcription, cell metabolism and cytoskeleton organization. Among the altered proteins, the level of macrophage migration inhibitory factor showed the largest alteration, which was confirmed with Western blot. Macrophage migration inhibitory factor showed widespread distribution and was predominantly expressed in astrocytes in the forebrain of rats which were described using immunohistochemistry. We conclude that neonatal clomipramine exposure induces sustained modification in the proteome, which may form the molecular basis of the observed depression-like behavior in adult rats. BIOLOGICAL SIGNIFICANCE: It is known that some of the psychiatric disorders, such as autism, depression or schizophrenia may be at least in part, developmental disorders. We hypothesized that clomipramine treatment in early stage of brain development, which is known to induce depression-like behavior in adult rats, results in pathological distortion in neuronal and glial network development, which can be reflected by the cellular proteome in adulthood. Thus, we performed an unbiased proteomics experiment in adult rats, which were neonatally administered with clomipramine to reveal protein level changes three months after treatment. Many of the identified changed proteins are previously associated with depressive symptoms, e.g., the macrophage migration inhibitory factor (MIF), the level of which showed the largest alteration among the identified proteins. Based on our data, we suggest that neonatal clomipramine treatment is a reliable model to study the developmental effect of psychoactive drugs applied in the sensitive early phase of brain development. Furthermore, our findings support the idea that the alteration of early development of the brain induced by antidepressant treatment could result in sustained pathological changes in the cellular phenotype in the prefrontal cortex leading to depression-like behavioral symptoms. PMID- 27371349 TI - A Cyclin D2-derived peptide acts on specific cell cycle phases by activating ERK1/2 to cause the death of breast cancer cells. AB - : Protein degradation by the proteasome generates functional intracellular peptides. Pep5, a peptide derived from Cyclin D2, induces cell death in tumor cell lines and reduces the volume of rat C6 glioblastoma tumors in vivo. Here, we chose the human MDA-MB-231 breast cancer cells to evaluate the mechanism of cell death induced by pep5 in different phases of the cell cycle. Fluorescently labeled pep5, monitored by real time confocal microscopy, entered the MDA-MB-231 cells 3min after application and localized to the nucleus and cytoplasm. Pep5 induced cell death was increased when the MDA-MB-231 cell population was arrested at the G1/S transition or in S phase compared to asynchronous cells. Pep5 induced permanent extracellular signal-regulated kinase (ERK1/2) phosphorylation in MDA MB-231 cells synchronized in G1/S or S phase. Affinity chromatography followed by mass spectrometry identified CLIC1 and Plectin as the only two proteins that interacted with pep5 in both asynchronous and synchronized MDA-MB-231 cells. These interactions could explain the long-lasting ERK1/2 phosphorylation and the cytoskeleton perturbations in the MDA-MB-231 cells, in which the stress fibers' integrity is affected by pep5 treatments. These data suggest that pep5 has potential therapeutic properties for treating specific types of cancers, such as breast cancer cells. BIOLOGICAL SIGNIFICANCE: Pep5, a natural intracellular peptide formed by the degradation of Cyclin D2 through the ubiquitin-proteasome system, induces cell death when reintroduced into MDA-MB-231 breast cancer cells, which express low levels of Cyclin D2, specifically in G1/S arrested cells or in cells that are passing through S phase. Under these conditions, pep5 is able to interact with different intracellular proteins, primarily cytoskeleton and proteasome components, which can lead to cellular apoptosis. Together, our data suggest that pep5 is an intracellular peptide with therapeutic potential for treating specific types of tumors with low expression of Cyclin D2 by inhibiting cell proliferation. PMID- 27371350 TI - iTRAQ-based quantitative proteomic analysis reveals the role of the tonoplast in fruit senescence. AB - The vacuole is by far the largest multifunctional organelle in fruits and plays a functional role in fruit development and fruit quality. Despite its significance, little information exists pertaining to the role of the vacuolar membrane (tonoplast) in the process of fruit senescence. In the present study, an iTRAQ based quantitative proteomic approach was used to characterize the dynamic alterations in the tonoplast proteome during fruit senescence. Tonoplasts were purified from apple fruit at various stages of senescence using an iodixanol step gradient protocol. A total of 345 tonoplast-related proteins were identified with diverse functions such as transporters and proton pumps, signal transduction, membrane fusion or vesicle trafficking, cellular metabolic process, defense response, protein folding and degradation, and cytoskeleton. Changes in protein abundance during storage were characterized for the identified proteins. A total of 22 proteins displayed differential levels of abundance during storage. The senescence-related tonoplast proteins mostly function in the transportation of metabolites, signal transduction, membrane trafficking, and stress response. RT qPCR analysis was used to quantify the level of expression of nine genes encoding some of the differentially abundant proteins. The results of this study provide new information regarding the function of the tonoplast during fruit senescence. BIOLOGICAL SIGNIFICANCE: Studies on the postharvest physiology and biochemistry of apple fruit have been conducted for several decades. Little proteomic information is available, however, pertaining to the role of the vacuole in fruit ripening and senescence. In the present study, an iTRAQ-based quantitative proteomic analysis was conducted on tonoplasts isolated from apple fruit in order to gain a global view of alterations in the tonoplast proteome during fruit senescence. The information obtained in the present study not only provides basic information about the tonoplast proteome in apple fruit but also characterized the quantitative changes that occur in the abundance of tonoplast proteins during the course of fruit senescence. This study provides a deeper insight into the cellular functions of the vacuole during fruit senescence that can serve as a basis for the development of future biotechnological strategies for the improvement of fruit quality. PMID- 27371351 TI - Poor compliance and lack of improvement in birth certificate reporting of assisted reproductive technology pregnancies in the United States. PMID- 27371353 TI - Cell-free DNA screening in clinical practice: abnormal autosomal aneuploidy and microdeletion results. AB - BACKGROUND: Since its commercial release in 2011 cell-free DNA screening has been rapidly adopted as a routine prenatal genetic test. However, little is known about its performance in actual clinical practice. OBJECTIVE: We sought to investigate factors associated with the accuracy of abnormal autosomal cell-free DNA results. STUDY DESIGN: We conducted a retrospective cohort study of 121 patients with abnormal cell-free DNA results from a referral maternal-fetal medicine practice from March 2013 through July 2015. Patients were included if cell-free DNA results for trisomy 21, trisomy 18, trisomy 13, or microdeletions (if reported by the laboratory) were positive or nonreportable. The primary outcome was confirmed aneuploidy or microarray abnormality on either prenatal or postnatal karyotype or microarray. Secondary outcomes were identifiable associations with in vitro fertilization, twins, ultrasound findings, testing platform, and testing laboratory. Kruskal-Wallis or Fisher exact tests were used as appropriate. RESULTS: A total of 121 patients had abnormal cell-free DNA results for trisomy 21, trisomy 18, trisomy 13, and/or microdeletions. In all, 105 patients had abnormal cell-free DNA results for trisomy 21, trisomy 18, and trisomy 13. Of these, 92 (87.6%) were positive and 13 (12.4%) were nonreportable. The results of the 92 positive cell-free DNA were for trisomy 21 (48, 52.2%), trisomy 18 (22, 23.9%), trisomy 13 (17, 18.5%), triploidy (2, 2.2%), and positive for >1 parameter (3, 3.3%). Overall, the positive predictive value of cell-free DNA was 73.5% (61/83; 95% confidence interval, 63-82%) for all trisomies (by chromosome: trisomy 21, 83.0% [39/47; 95% confidence interval, 69-92%], trisomy 18, 65.0% [13/20; 95% confidence interval, 41-84%], and trisomy 13, 43.8% [7/16; 95% confidence interval, 21-70%]). Abnormal cell-free DNA results were associated with positive serum screening (by group: trisomy 21 [17/48, 70.8%]; trisomy 18 [7/22, 77.8%]; trisomy 13 [3/17, 37.5%]; nonreportable [2/13, 16.7%]; P = .004), and abnormal first-trimester ultrasound (trisomy 21 [25/45, 55.6%]; trisomy 18 [13/20, 65%]; trisomy 13 [6/14, 42.9%]; nonreportable [1/13, 7.7%]; P = .003). There was no association between false-positive rates and testing platform, but there was a difference between the 4 laboratories (P = .018). In all, 26 patients had positive (n = 9) or nonreportable (n = 17) microdeletion results. Seven of 9 screens positive for microdeletions underwent confirmatory testing; all were false positives. CONCLUSION: The positive predictive value of 73.5% for cell-free DNA screening for autosomal aneuploidy is lower than reported. The positive predictive value for microdeletion testing was 0%. Diagnostic testing is needed to confirm abnormal cell-free DNA results for aneuploidy and microdeletions. PMID- 27371352 TI - Maternal dietary intake during pregnancy and offspring body composition: The Healthy Start Study. AB - BACKGROUND: Consistent evidence of an influence of maternal dietary intake during pregnancy on infant body size and composition in human populations is lacking, despite robust evidence in animal models. OBJECTIVE: We sought to evaluate the influence of maternal macronutrient intake and balance during pregnancy on neonatal body size and composition, including fat mass and fat-free mass. STUDY DESIGN: The analysis was conducted among 1040 mother-offspring pairs enrolled in the prospective prebirth observational cohort: the Healthy Start Study. Diet during pregnancy was collected using repeated 24-hour dietary recalls (up to 8). Direct measures of body composition were obtained using air displacement plethysmography. The National Cancer Institute measurement error model was used to estimate usual dietary intake during pregnancy. Multivariable partition (nonisocaloric) and nutrient density (isocaloric) linear regression models were used to test the associations between maternal dietary intake and neonatal body composition. RESULTS: The median macronutrient composition during pregnancy was 32.2% from fat, 15.0% from protein, and 47.8% from carbohydrates. In the partition multivariate regression model, individual macronutrient intake values were not associated with birthweight or fat-free mass, but were associated with fat mass. Respectively, 418 kJ increases in total fat, saturated fat, unsaturated fat, and total carbohydrates were associated with 4.2-g (P = .03), 11.1-g (P = .003), 5.9-g (P = .04), and 2.9-g (P = .02) increases in neonatal fat mass, independent of prepregnancy body mass index. In the nutrient density multivariate regression model, macronutrient balance was not associated with fat mass, fat free mass, or birthweight after adjustment for prepregnancy body mass index. CONCLUSION: Neonatal adiposity, but not birthweight, is independently associated with increased maternal intake of total fat, saturated fat, unsaturated fat, and total carbohydrates, but not protein, suggesting that most forms of increased caloric intake contribute to fetal fat accretion. PMID- 27371354 TI - Medical management of ectopic pregnancy with single-dose and 2-dose methotrexate protocols: human chorionic gonadotropin trends and patient outcomes. AB - BACKGROUND: Ectopic pregnancy, although rare, is an important cause of female morbidity and mortality and early, effective treatment is critical. Systemic methotrexate has become widely accepted as a safe and effective alternative to surgery in the stable patient. As the number and timing of methotrexate doses differ in the 3 main medical treatment regimens, one might expect trends in serum human chorionic gonadotropin and time to resolution to vary depending on protocol. Furthermore, human chorionic gonadotropin trends and time to resolution may predict ultimate treatment success. OBJECTIVE: This study hypothesized that the 2-dose methotrexate protocol would be associated with a faster initial decline in serum human chorionic gonadotropin levels and a shorter time to resolution compared to the single-dose protocol. STUDY DESIGN: A prospective multicenter cohort study included clinical data from women who received medical management for ectopic pregnancy. Rates of human chorionic gonadotropin change and successful pregnancy resolution were assessed. Propensity score modeling addressed confounding by indication, the potential for differential assignment of patients with better prognosis to the single-dose methotrexate protocol. RESULTS: In all, 162 ectopic pregnancies were in the final analysis; 114 (70%) were treated with the single-dose methotrexate and 48 (30%) with the 2-dose protocol. Site, race, ethnicity, and reported pain level were associated with differential protocol allocation (P < .001, P = .011, P < .001, and P = .035, respectively). Women had similar initial human chorionic gonadotropin levels in either protocol but the mean rate of decline of human chorionic gonadotropin from day 0 (day of administration of first dose of methotrexate) to day 7 was significantly more rapid in women who received the single-dose protocol compared to those treated with the 2-dose protocol (mean change -31.3% vs -10.4%, P = .037, adjusted for propensity score and site). The 2 protocols had no significant differences in success rate or time to resolution. CONCLUSION: In a racially and geographically diverse group of women, the single- and double-dose methotrexate protocols had comparable outcomes. The more rapid human chorionic gonadotropin initial decline in the single-dose group suggested these patients were probably at lower risk for ectopic rupture than those getting the 2-dose protocol. A prospective randomized controlled design is needed to remove confounding by indication. PMID- 27371356 TI - ? PMID- 27371355 TI - Statin use and uterine fibroid risk in hyperlipidemia patients: a nested case control study. AB - BACKGROUND: Statins are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors primarily used for treatment of hyperlipidemia. Recently, they have been shown to inhibit proliferation of uterine fibroid cells and inhibit tumor growth in fibroid animal models. OBJECTIVE: We sought to examine the association between statin use and the risk of uterine fibroids and fibroid-related symptoms in a nationally representative sample of commercially insured women diagnosed with hyperlipidemia. STUDY DESIGN: We performed a nested case-control study of >190,000 women enrolled in one of the nation's largest commercial health insurance programs. From a cohort of women aged 18-65 years diagnosed with hyperlipidemia from January 2004 through March 2011, we identified 47,713 cases (women diagnosed with uterine fibroids) and 143,139 controls (women without uterine fibroids) matched at a 1:3 ratio on event/index date (month and year) and age (+/-1 year). We used conditional and unconditional logistic regression to calculate odds ratios and 95% confidence intervals for the risk of uterine fibroids and fibroid-related symptoms associated with prior use of statins. RESULTS: Exposure to statins within 2 years before the event/index date was associated with a decreased risk of uterine fibroids (odds ratio, 0.85; 95% confidence interval, 0.83-0.87). In a separate subanalysis restricted to cases, statin users had a lower likelihood of having menorrhagia (odds ratio, 0.88; 95% confidence interval, 0.84-0.91), anemia (odds ratio, 0.84; 95% confidence interval, 0.79-0.88), or pelvic pain (odds ratio, 0.85; 95% confidence interval, 0.81-0.91) and of undergoing myomectomy (odds ratio, 0.76; 95% confidence interval, 0.66-0.87) compared to nonusers. CONCLUSION: The use of statins was associated with a lower risk of uterine fibroids and fibroid-related symptoms. Further studies, including randomized controlled trials, may be warranted. PMID- 27371357 TI - [Hematidrosis and hemolacrea associated with conversion disorder. About a pediatric case]. PMID- 27371358 TI - [Perianal pemphigus vegetans]. PMID- 27371359 TI - Characterization of the sensor domain of QseE histidine kinase from Escherichia coli. AB - In enterohemorrhagic Escherichia coli (EHEC), the QseEF two-component system causes attaching and effacing (AE) lesion on epithelial cells. QseE histidine kinase senses the host hormone epinephrine, sulfate, and phosphate; it also regulates QseF response regulator, which activates LEE gene that encodes AE lesion. In order to understand the recognition of ligand molecules and signal transfer mechanism in pathogenic bacteria, structural studies of the sensor domain of QseE of Escherichia coli should be conducted. In this study, we describe the overexpression, purification, and structural and biophysical properties of the sensor domain of QseE. The fusion protein had a 6*His tag at its N-terminus; this protein was overexpressed as inclusion bodies in E. coli BL21 (DE3). The protein was denatured in 7M guanidine hydrochloride and refolded by dialysis. The purification of the refolded protein was carried out using Ni NTA affinity column and size-exclusion chromatography. Thereafter, the characteristics of the refolded protein were determined from NMR, CD, and MALS spectroscopies. In a pH range of 7.4-5.0, the folded protein existed in a monomeric form with a predominantly helical structure. (1)H-(15)N HSQC NMR spectra shows that approximately 93% backbone amide peaks are detected at pH 5.0, suggesting that the number of backbone signals is sufficient for NMR studies. These data might provide an opportunity for structural and functional studies of the sensor domain of QseE. PMID- 27371361 TI - Complement research in the 18th-21st centuries: Progress comes with new technology. AB - The complement system has been studied for about 120 years. Progress in defining this large and complex system has been dependent on the research technologies available, but since the introduction of protein chromatography, electrophoresis, and antibody-based assay methods in the 1950s and 60s, and sequencing of proteins and DNA in the 70s and 80s, there has been very rapid accumulation of data. With more recent improvements in 3D structure determination (nmr and X-ray crystallography), the structures of most of the complement proteins have now been solved. Complement research since 1990 has been greatly stimulated by the discoveries of the multiple proteins in the lectin pathway, the strong association of Factor H, C3, Factor B allelic variants with adult macular degeneration and atypical haemolytic uremic syndrome, and the introduction of the anti-C5 monoclonal antibody as a therapy for paroxysmal nocturnal hemoglobinuria and atypical haemolytic uremic syndrome. Potential new roles for complement in tissue development and the search for novel therapeutics suggest a very active future for complement research. PMID- 27371360 TI - Trends in the Diagnosis and Outcomes of Traumatic Carotid and Vertebral Artery Dissections among Medicare Beneficiaries. AB - BACKGROUND: Early identification of carotid and vertebral artery dissections has been advocated to reduce stroke among trauma patients. We sought to characterize trends in the diagnosis of traumatic carotid and vertebral artery dissections and association changes in stroke rate among Medicare beneficiaries. METHODS: Using Medicare claims, we created a cohort of 5,961 beneficiaries admitted with a new traumatic carotid or vertebral artery dissection from 2001 to 2012. We calculated rates of stroke during hospitalization and 90 days of discharge. We calculated rates of carotid imaging using computed tomography-angiography, carotid duplex, and plain angiography index hospitalization. To study concurrent secular trends, we created a secondary cohort of patients admitted after any traumatic injury from 2001 to 2012 and determined rates of stroke and carotid imaging within this cohort. RESULTS: From 2001 to 2012, incidence of traumatic carotid dissection increased 72% among Medicare beneficiaries (1.1-1.76 per 100,000 patients; rate ratio [RR], 1.72; 95% CI, 1.6-1.9, P < 0.001). Among patients diagnosed with traumatic carotid or vertebral artery dissections, the combined in-hospital and 90-day stroke rate did not change significantly (4.9% in 2001; 5.2% in 2012; RR, 1.06; 95% CI, 0.93-1.20; P = 0.094). Likewise, there was little change in mortality (10.3%; RR, 1.01; 95% CI, 0.95-1.06; P = 0.88). Among all trauma patients, the use of computed tomography angiography has increased 16-fold (2-35 per 100,000 patients; RR, 16.7; 95% CI, 13-19; P < 0.0001). CONCLUSIONS: Despite increased diagnosis of carotid or vertebral artery dissection, there has been little change in stroke risk among trauma patients. Efforts to more effectively target imaging and treatment for these patients are necessary. PMID- 27371362 TI - Vaginal Cytology Results in Follow-up of Endometrial Carcinoma After Hysterectomy. AB - OBJECTIVES: Our study examined accumulated data on vaginal cytology follow-up results of women treated for endometrial carcinoma (EmCa) by hysterectomy in a large academic women's hospital practice. METHODS: This study analyzed cases of EmCa treated by hysterectomy from January 2006 to December 2008 with documented follow-up vaginal cytology and/or vaginal biopsy results available prior to September 2013. RESULTS: Of 607 patients with EmCa who had documented hysterectomy findings, 420 had either follow-up vaginal biopsy or cytology results during a mean follow-up period of 42.5 months, and 414 (98.6%) had at least one vaginal cytology follow-up result. Of 414 patients followed with vaginal cytology results, 48 (11.6%) had biopsy results while 366 (88.4%) had only vaginal cytology results. Recurrent EmCa in the vagina was documented by biopsy in 11 patients, eight within 2 years of hysterectomy. Cytology findings of neoplastic glandular cells triggered diagnostic vaginal biopsies in two of 11 cases. CONCLUSIONS: Vaginal recurrences of EmCa were diagnosed in 11 (2.6%) of 420 patients with documented vaginal follow-up testing. Abnormal vaginal cytology findings directly led to vaginal biopsy diagnoses of EmCa in two of the 11 patients. Vaginal cytology is no longer a recommended routine surveillance option for detection of vaginal cuff recurrence of EmCa. PMID- 27371363 TI - Thymomas With Extensive Clear Cell Component: A Clinicopathologic and Immunohistochemical Study of Nine Cases. AB - OBJECTIVES: Nine cases of thymomas with an extensive clear cell component are presented. METHODS: The patients were six men and three women aged between 45 and 62 years (mean, 52 years). Presenting symptoms included shortness of breath, chest pain, and cough. Diagnostic imaging revealed anterior mediastinal masses in all patients, and all underwent thymectomy. RESULTS: Grossly, the tumors varied from 3 to 9 cm in the greatest dimension. Four cases were invasive and five encapsulated. Histologically, the tumors were characterized by an epithelial cell component with extensive clear cell change, admixed with lymphocytes in varying proportions. Immunohistochemically, the tumors demonstrated the typical immunophenotype of thymomas characterized by positive staining of the epithelial cells for pancytokeratin and cytokeratin 5/6, absent expression of CD5 and c-kit, and reactivity of the lymphocytes for terminal deoxynucleotidyl transferase. Clinical follow-up available for six patients showed that all were alive and well 12 to 24 months after surgical resection. CONCLUSIONS: The cases herein presented highlight an unusual feature in thymoma that has more commonly been ascribed to thymic carcinoma. They also emphasize the importance of correct diagnosis to determine the appropriate treatment strategy and to accurately predict prognosis. PMID- 27371364 TI - [The current aspects of the use of ecstasy/MDMA in France]. AB - Methylenedioxymethamphetamine (MDMA), the active compound of ecstasy, has been used for several years, especially by young adults to benefit of psychostimulant properties. By raising the level of neuromodulators in the synapsis, MDMA can cause psychiatric and physical injuries. After reduced supplies in 2009 (number of ecstasy seizures equal to 10 percent of those recorded in 2002), judicial authorities now observed an increased availability (a half more part of seizures in 2012 than 2010). From its "Spontaneous Notifications" data base and "deaths in connection with the abuse of medicine and substances (DRAMES)", "observation of illegal drugs and misuse of psychotropic medications" (OPPIDUM), and "observation of drug dependencies in ambulatory medicine" (OPEMA) national inquiries, the French Addictovigilance network (CEIP-A) highlighted the increasing consumption of MDMA. The way of use appeared quite unchanged: users were mainly young men between 25 and 30 years; they favored an occasional use but mainly combined other products such as alcohol, cannabis and other stimulants. Severity of the clinical cases, based on hospital care and forensic data, could be consistent with the higher amounts of MDMA measured in pills. PMID- 27371366 TI - [Not Available]. PMID- 27371365 TI - In Parkinson's disease STN stimulation enhances responsiveness of movement initiation speed to high reward value. AB - OBJECTIVE: The subthalamic nucleus (STN) is part of the motor, associative, and limbic cortico-striatal circuits through which it can influence a range of behaviours, with preclinical and clinical evidence suggesting that the STN is involved in motivational modulation of behaviour. In the present study, we investigated if in Parkinson's disease (PD) motivational modulation of movement speed is altered by deep brain stimulation (DBS) of the STN (STN-DBS). METHODS: We studied the effect of monetary incentive on speed of movement initiation and execution in a computer-based simple reaction time task in 10 operated patients with Parkinson's disease using a STN DBS ON/OFF design and also in 11 healthy participants. RESULTS: Prospect of reward improved speed of movement initiation in PD patients both with STN-DBS ON and OFF. However, only with STN-DBS ON, the patients showed greater speeding of initiation time with higher reward magnitude, suggesting enhanced responsivity to higher reward value. Also, on the rewarded trials, PD patients ON stimulation made more anticipation errors than on unrewarded trials, reflecting a propensity to impulsive responses triggered by prospect of reward by subthalamic stimulation. The motivational modulation of movement speed was preserved and enhanced in PD with STN-DBS. CONCLUSION: Motivational modulation of movement speed in PD is maintained with STN-DBS, with STN stimulation having a further energizing effect on movement initiation in response to greater incentive value. Our results suggest that STN plays a role in integrating motivational influences into motor action, which may explain some previous reports of STN-DBS induced impulsivity with increased motivational salience of stimuli. PMID- 27371367 TI - An assessment of dietary exposure to glyphosate using refined deterministic and probabilistic methods. AB - Glyphosate is a herbicide used to control broad-leaved weeds. Some uses of glyphosate in crop production can lead to residues of the active substance and related metabolites in food. This paper uses data on residue levels, processing information and consumption patterns, to assess theoretical lifetime dietary exposure to glyphosate. Initial estimates were made assuming exposure to the highest permitted residue levels in foods. These intakes were then refined using median residue levels from trials, processing information, and monitoring data to achieve a more realistic estimate of exposure. Estimates were made using deterministic and probabilistic methods. Exposures were compared to the acceptable daily intake (ADI)-the amount of a substance that can be consumed daily without an appreciable health risk. Refined deterministic intakes for all consumers were at or below 2.1% of the ADI. Variations were due to cultural differences in consumption patterns and the level of aggregation of the dietary information in calculation models, which allows refinements for processing. Probabilistic exposure estimates ranged from 0.03% to 0.90% of the ADI, depending on whether optimistic or pessimistic assumptions were made in the calculations. Additional refinements would be possible if further data on processing and from residues monitoring programmes were available. PMID- 27371368 TI - Irreversible down-regulation of miR-375 in the livers of Fischer 344 rats after chronic furan exposure. AB - Furan, a rodent liver carcinogen, is a chemical contaminant found in a broad range of cooked foods. Despite a lack of conclusive evidence regarding furan genotoxicity, several reports indicate that furan induces a broad range of non genotoxic alterations, including aberrant expression microRNAs (miRNAs). In order to clarify the role of miRNA alterations with respect to furan carcinogenicity, we investigated the expression of several cancer-related miRNAs in the livers of Fischer 344 rats treated continuously with furan. The results demonstrate that furan induced marked changes in miRNA expression, characterized by over expression of hepatic miRNAs, miR-34a, miR-93, miR-200a, miR-200b, and miR-224, and down-regulation of miR-375. Interestingly, a majority of furan-induced miRNA changes diminished after the cessation of the furan treatment. In contrast, the expression of miR-375 steadily decreased in a time-dependent manner following furan treatment. The reduced expression of miR-375 was accompanied by cytosine DNA hypermethylation and increased lysine methylation of histone H3K9 and H3K27 at the MiR-375 gene. The significance of miR-375 inhibition with respect to the pathogenesis of furan-induced liver toxicity and carcinogenicity may be attributed to its role in the up-regulation of Yes-associated protein 1 (YAP1), which is one of the principal events in the liver carcinogenesis. The results of the present study support the hypothesis of the non-genotoxic mode of action of furan and emphasize the importance of epigenetic alterations in the mechanism of furan hepatotoxicity. PMID- 27371369 TI - Difference-in-Differences Method in Comparative Effectiveness Research: Utility with Unbalanced Groups. AB - BACKGROUND: Comparative effectiveness research (CER) often includes observational studies utilizing administrative data. Multiple conditioning methods can be used for CER to adjust for group differences, including difference-in-differences (DiD) estimation. OBJECTIVE: This study presents DiD and demonstrates how to apply this conditioning method to estimate treatment outcomes in the CER setting by utilizing the MarketScan(r) Databases for multiple sclerosis (MS) patients receiving different therapies. METHODS: The sample included 6762 patients, with 363 in the Test Cohort [glatiramer acetate (GA) switched to fingolimod (FTY)] and 6399 in the Control Cohort (GA only, no switch) from a US administrative claims database. A trend analysis was conducted to rule out concerns regarding regression to the mean and to compare relapse rates among treatment cohorts. DiD analysis was used to enable comparisons among the Test and Control Cohorts. Logistic regression was used to estimate the probability of relapse after switching from GA to FTY, and to compare group differences in the pre- and post index periods. RESULTS: Crude DiD analysis showed that in the pre-index period more patients in the Test Cohort experienced an MS relapse and had a higher mean number of relapses than in the Control Cohort. During the pre-index period, numeric and relative data for MS relapses in patients in the Test Cohort were significantly higher than in the Control Cohort, while no significant between group differences emerged during the post-index period. Generalized linear modeling with DiD regression estimation showed that the mean number of MS relapses decreased significantly in the post-index period among patients in the Test Cohort compared with patients in the Control Cohort. CONCLUSION: In this study, an MS population was utilized to demonstrate how DiD can be applied to estimate treatment effects in a heterogeneous population, where the Test and Control Cohorts varied greatly. The results show that DiD offers a robust method for comparing diverse cohorts when other risk-adjustment methods may not be adequate. PMID- 27371370 TI - Gut Microbiota Developments With Emphasis on Inflammatory Bowel Disease: Report From the Gut Microbiota for Health World Summit 2016. PMID- 27371371 TI - Elastic Characteristics of the Normal Achilles Tendon Assessed by Virtual Touch Imaging Quantification Shear Wave Elastography. AB - OBJECTIVES: To assess the elastic properties of the normal Achilles tendon in different age groups by Virtual Touch imaging quantification (VTIQ; Siemens Medical Solutions, Malvern, PA) shear wave elastography. METHODS: A total of 326 healthy volunteers older than 18 years were divided into different groups by sex and age. The thickness, shear wave velocity (SWV) in sagittal and axial sections, and anisotropic coefficient of the Achilles tendon in a state of relaxation were obtained by conventional sonography and Virtual Touch imaging quantification elastography. These parameters were compared in different age and sex groups, and their correlations with age were evaluated. RESULTS: The thickness of the Achilles tendon in men and women increased gradually with age, and it was larger in men than in women in each age group (P < .05). The SWV of the tendon in the sagittal section decreased slightly with age, but the sagittal and axial SWVs and anisotropic coefficient had no significant differences among different age groups (P > .05), and they also had no significant differences between men and women within any group (P > .05). The SWVs in the sagittal and axial sections and anisotropic coefficient had no correlation with age. Intraclass correlation coefficients for sagittal and axial SWVs obtained by 2 independent observers were 0.923 and 0.870, respectively. CONCLUSIONS: The thickness of the Achilles tendon increased gradually with age. We confirmed that tendinous elastographic anisotropy and the stiffness of the tendon had no significant correlation with age. PMID- 27371372 TI - Peripherally Inserted Central Catheter-Related Upper Extremity Venous Thrombosis in Oncology Patients: A Prospective Study Based on Doppler Sonography. AB - OBJECTIVES: Peripherally inserted central catheters (PICCs) are associated with an increased risk of venous thrombosis. This study had 2 objectives: to estimate the incidence of upper extremity venous thrombosis associated with PICCs in oncology patients and to evaluate the role of Doppler sonography in antithrombotic prophylaxis. METHODS: We conducted a prospective study with each patient being followed for 6 weeks. From April 2014 to October 2014, we analyzed a series of 245 consecutive oncology patients undergoing chemotherapy via PICCs, for an overall number of 246 PICC placements. We assessed the role of Doppler sonography for initiation of antithrombotic prophylaxis. The study group encompassed 2 cohorts of patients: those who received regular weekly Doppler screening for thrombosis prophylaxis and those who did not. RESULTS: Of 246 insertions, we observed 90 episodes of upper extremity venous thrombosis (36.59%); 62 of them were asymptomatic in the Doppler group, and 28 were symptomatic in the no-Doppler group. Patients in the Doppler group had a significantly lower rate of thrombosis (0%) than those in the no-Doppler group (23.53%; P < .01). CONCLUSIONS: Our prospective study suggests that the rate of PICC-related upper extremity venous thrombosis in oncology patients is high, and the occurrence of symptomatic thrombosis could be lowered with regular weekly Doppler screening after PICC insertions. PMID- 27371373 TI - Transient Elastography for Spleen Stiffness Measurement in Patients With Cirrhosis: Role in Degree of Thrombocytopenia. AB - OBJECTIVES: The purpose of our study was to evaluate the relationship between spleen stiffness measured by transient elastography and the degree of thrombocytopenia in patients with liver cirrhosis. METHODS: A total of 67 patients with liver cirrhosis were prospectively enrolled in the study. All patients underwent single-day hematologic and biochemical tests, sonography, and transient elastography of the liver and spleen. Thrombocytopenia was categorized as mild (platelet count, 75,000-150,000/MUL), moderate (50,000-75,000/MUL), and severe (<50,000/MUL). RESULTS: The degree of thrombocytopenia was significantly correlated with spleen stiffness (P = .001) and spleen size (P = .002) but not with liver stiffness (P = .086). In patients without splenomegaly, spleen stiffness values were significantly higher in patients with thrombocytopenia than in those without thrombocytopenia (P = .035). In patients with splenomegaly, spleen stiffness values were significantly higher in patients with moderate to severe thrombocytopenia than in those with a normal platelet count or mild thrombocytopenia (P = .007). Compared to liver stiffness, spleen stiffness showed a better and statistically significant correlation with platelet count and spleen size in patients with cirrhosis. CONCLUSIONS: The degree of thrombocytopenia was directly correlated with spleen stiffness, irrespective of the presence of splenomegaly. The clinical phenomenon of unexpected thrombocytopenia may be explained by a subtle or irreversible change in spleen stiffness. PMID- 27371374 TI - High-Frequency Color Doppler Sonography of Bullous Pemphigoid: Correlation With Histologic Findings. AB - Bullous pemphigoid is the most frequent autoimmune-mediated blistering skin disease, belonging to the group of subepidermal bullae. We performed high frequency color Doppler sonography in 3 cases of bullous pemphigoid, in bullous and adjacent non-bullous skin, which showed homogeneous sonographic findings. Subepidermal cystic structures with dermal hypoechogenicity were observed in bullous skin. In nonbullous skin, the dermis showed hypoechogenicity compared to normal skin. Color Doppler signals were increased in both areas. These findings correlate histologically with subepidermal bullae and dermal inflammatory infiltrates. PMID- 27371375 TI - Intrarenal Reflux: Diagnosis at Contrast-Enhanced Voiding Urosonography. AB - Vesicoureteral reflux (VUR) is a childhood condition that is usually diagnosed by fluoroscopic voiding cystourethrography (VCUG). Intrarenal reflux (IRR) of infected urine is believed to play an important role in the pathogenesis of reflux-associated pyelonephritis and subsequent parenchymal scarring and is traditionally depicted by fluoroscopic VCUG. This case series describes the phenomenon of IRR occurring in association with VUR in 4 children as depicted by contrast-enhanced voiding urosonography. The ability of contrast-enhanced voiding urosonography to show IRR when it occurs in conjunction with VUR compares favorably to that of fluoroscopic VCUG. PMID- 27371376 TI - Subcutaneous Angioleiomyoma: Clinical and Sonographic Features With Histopathologic Correlation. AB - OBJECTIVES: To investigate clinical and sonographic features of subcutaneous angioleiomyoma with histopathologic correlation. METHODS: Clinical features of 141 cases and sonographic appearances of 33 cases of histopathologically proven subcutaneous angioleiomyoma were retrospectively reviewed. Clinical information included patient age, sex, tumor location, and symptoms. Sonographic features included tumor size, location, contour, margin, component, echogenicity, calcifications, and vascularity. Sonograms were analyzed with histopathologic correlation by a single radiologist and a single pathologist. RESULTS: Clinical features of the 141 cases of angioleiomyoma included the following: 78.0% of the cases (110 of 141) were on the lower leg or ankle; 55.3% of the patients (78 of 141) had pain at the tumor location; the female-to-male ratio was 1.61:1.00, and most cases occurred in patients in the third through sixth decades. Sonographic features of the 33 cases of angioleiomyoma included the following: 85.0% of the cases (28 of 33) were smaller than 20 mm; 94.0% to 97.0% were solid, oval, parallel to the skin, well defined, and homogeneously hypoechoic and without calcifications; 75.8% (25 of 33) were superficially located, close to or in contact with the dermis; and 39.4% (13 of 33) showed low or moderate internal vascularity. CONCLUSIONS: Typical clinical and sonographic features of angioleiomyoma may include a female patient with a painful lower leg or ankle subcutaneous mass, a superficial location, especially in contact with the dermis, a small size (<20 mm), an oval shape, a parallel orientation to the skin, well defined margins, complete solid components, homogeneous hypoechogenicity, low or moderate vascular density, and absence of calcifications. PMID- 27371377 TI - Erratum to: Pontibacter locisalis Sy30T sp. nov. isolated from soil collected from an abandoned saltern. PMID- 27371378 TI - Altererythrobacter aurantiacus sp. nov., isolated from deep-sea sediment. AB - A Gram-negative, aerobic, coccoid bacterium, strain O30(T), was isolated from a deep-sea sediment sample collected from the west Pacific. 16S rRNA gene sequence analysis revealed that this strain is affiliated with the family Erythrobacteraceae in the class Alphaproteobacteria, and is closely related to the members of the genera Erythromicrobium (96.6 %), Porphyrobacter (95.5-96.3 %), Altererythrobacter (94.1-96.2 %) and Erythrobacter (94.2-96.2 %). Phylogenetic analysis including all described species of the family Erythrobacteraceae revealed that the isolate forms a clade in the cluster of the genus Altererythrobacter. Strain O30(T) was found to grow at 4-40 degrees C, pH 6.0-10.0 and in the presence of 0.5-7.0 % (w/v) NaCl. Chemotaxonomic analysis revealed ubiquinones Q-8, Q-9 and Q-10 as the predominant respiratory quinones, summed feature 8 (C18:1 omega7c and/or C18:1 omega6c), C17:1 omega6c and C16:0 as major fatty acids, and diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and sphingoglycolipid as the major polar lipids. The DNA G + C content was determined to be 56.9 mol %. On the basis of phenotypic and genotypic data presented in this study, strain O30(T) represents a novel species within the genus Altererythrobacter, for which the name Altererythrobacter aurantiacus sp. nov. is proposed; the type strain is O30(T) (= CGMCC 1.12762(T) = JCM 19853(T) = LMG 28110(T) = MCCC 1A09962(T)). PMID- 27371379 TI - Assessment of technical and nontechnical skills in surgical residents. AB - BACKGROUND: Surgical competence encompasses both technical and nontechnical skills. This study seeks to evaluate the validity evidence for a comprehensive surgical skills examination and to examine the relationship between technical and nontechnical skills. METHODS: Six examination stations assessing both technical and nontechnical skills, conducted yearly for surgical trainees (n = 120) between 2010 and 2014 are included. RESULTS: The assessment tools demonstrated acceptable internal consistency. Interstation reliability for technical skills was low (alpha = .39). Interstation reliability for the nontechnical skills was lower (alpha range -.05 to .31). Nontechnical skills domains were strongly correlated, ranging from r = .65, P < .001 to .86, P < .001. The associations between nontechnical and technical skills were inconsistent, ranging from poor (r = -.06; P = .54) to moderate (r = .45; P < .001). CONCLUSIONS: Multiple samplings of integrated technical and nontechnical skills are necessary to assess overall surgical competency. PMID- 27371380 TI - Extreme Postnatal Scaling in Bat Feeding Performance: A View of Ecomorphology from Ontogenetic and Macroevolutionary Perspectives. AB - Ecomorphology studies focus on understanding how anatomical and behavioral diversity result in differences in performance, ecology, and fitness. In mammals, the determinate growth of the skeleton entails that bite performance should change throughout ontogeny until the feeding apparatus attains its adult size and morphology. Then, interspecific differences in adult phenotypes are expected to drive food resource partitioning and patterns of lineage diversification. However, Formal tests of these predictions are lacking for the majority of mammal groups, and thus our understanding of mammalian ecomorphology remains incomplete. By focusing on a fundamental measure of feeding performance, bite force, and capitalizing on the extraordinary morphological and dietary diversity of bats, we discuss how the intersection of ontogenetic and macroevolutionary changes in feeding performance may impact ecological diversity in these mammals. We integrate data on cranial morphology and bite force gathered through longitudinal studies of captive animals and comparative studies of free-ranging individuals. We demonstrate that ontogenetic trajectories and evolutionary changes in bite force are highly dependent on changes in body and head size, and that bats exhibit dramatic, allometric increases in bite force during ontogeny. Interspecific variation in bite force is highly dependent on differences in cranial morphology and function, highlighting selection for ecological specialization. While more research is needed to determine how ontogenetic changes in size and bite force specifically impact food resource use and fitness in bats, interspecific diversity in cranial morphology and bite performance seem to closely match functional differences in diet. Altogether, these results suggest direct ecomorphological relationships at ontogenetic and macroevolutionary scales in bats. PMID- 27371381 TI - New Perspectives on the Ontogeny and Evolution of Avian Locomotion. AB - Close correspondence between form and function is a central tenet of natural selection. One of the most striking, textbook cases for form-function congruence is the evolution of flight and the body plan of birds: compared with other tetrapods, extant adult birds have highly modified integuments and skeletons, and it has traditionally been assumed that many of these modifications are adaptations or exaptations for flight. However, developing birds that lack many of the morphological signatures of flight capacity nevertheless use their developing wings for a variety of flapping behaviors, such as wing-assisted incline running and even brief flight. Immature birds thereby demonstrate that rudimentary "flight" apparatuses are more functional than traditional assumptions about form-function relationships would predict. Here, I review the ontogeny of avian locomotion, highlighting how the developmental acquisition of flight in extant birds can improve our understanding of form-function relationships in the avian body plan, and provide insight into the evolutionary origin of flight among extinct non-avian theropod dinosaurs. PMID- 27371382 TI - Ecology and Evolution of Phenotypic Plasticity in the Penis and Cirri of Barnacles. AB - Most barnacles are sessile, simultaneous hermaphrodites that reproduce by copulation. This is achieved through the extension of a muscular penis, famous for being the proportionally largest in the animal kingdom. The penis is a long cylindrical or conical organ, composed of a series of folded rings, allowing it to stretch to great lengths. The penises are covered with chemosensory setae allowing them to seek out receptive neighbors. For many species, the condition of the penis changes seasonally. In the most extreme circumstances, it degenerates and is shed during the first post-mating molt and is re-grown for the next mating season. Barnacle penises have been shown to exhibit phenotypic plasticity in response to many different challenges. When exposed to heavy waves, diameter is increased by thickening both the cuticle and muscles. When mates are far, length increases by adding ringed annulations. Experiments have shown that these plastic traits are modular, capable of changing independently from each other and that they improve mating ability. Alternate strategies to increase reproductive ability by barnacles include the production of dwarf and complemental males, sperm casting and sperm leakage, and aerial copulation. All of these mating strategies may have important implications for the study of reproductive biology, life history, and sex allocation theory. PMID- 27371383 TI - The Use of Filter-feeders to Manage Disease in a Changing World. AB - Rapid environmental change is linked to increases in aquatic disease heightening the need to develop strategies to manage disease. Filter-feeding species are effective biofilters and can naturally mitigate disease risk to humans and wildlife. We review the role of filter-feeders, with an emphasis on bivalves, in altering disease outcomes via augmentation and reduction. Filtration can reduce transmission by removing pathogens from the water column via degradation and release of pathogens in pseudofeces. In other cases, filtration can increase pathogen transmission and disease risk. The effect of filtration on pathogen transmission depends on the selectivity of the filter-feeder, the degree of infectivity by the pathogen, the mechanism(s) of pathogen transmission and the ability of the pathogen to resist degradation. For example, some bacteria and viruses can resist degradation and accumulate within a filter-feeder leading to disease transmission to humans and other wildlife upon ingestion. Since bivalves can concentrate microorganisms, they are also useful as sentinels for the presence of pathogenic microorganisms. While somewhat less studied, other invertebrates, including ascidians and sponges may also provide ecosystem services by altering pathogen transmission. In all scenarios, climate change may affect the potential for filter-feeders to mitigate disease risk. We conclude that an assessment including empirical data and modeling of system-wide impacts should be conducted before selection of filter-feeders to mitigate disease. Such studies should consider physiology of the host and microbe and risk factors for negative impacts including augmentation of other pathogens. PMID- 27371384 TI - Personality and Social Networks: A Generative Model Approach. AB - Social network analysis has produced important insights regarding the causes and consequences of animal social structure. Social structure has been shown to impact longevity, reproductive success, transmission of pathogens and information, and also play important role in the evolution of cooperation. Studies of the determinants of social structure have identified environmental, genetic, and structural factors in a variety of species. At the same time, most studies in the field have been descriptive in approach, statistically identifying patterns in social networks constructed from observed interactions. We argue that there is a need for predictive theory to complement descriptive studies, moving the field from pattern to process. As an example, we provide a simple model of the effect of personality on social network structure and social role differentiation. Our model suggests that variation in behavioral types can result in variation in individual social network traits, and that some patterns found in animal networks in the wild, such as assortativity with respect to personality, may be outcomes of social inheritance and individual variation in it. Our approach and results exemplify the potential of generative models to connect individual-level processes to emergent patterns and advance our understanding of social complexity in nature. PMID- 27371385 TI - MULTIFUNCin: A Multifunctional Protein Cue Induces Habitat Selection by, and Predation on, Barnacles. AB - Foundation species provide critical resources to ecological community members and are major determinants of biodiversity. The barnacle Balanus glandula is one such species and dominates space among the higher reaches on wave-swept shores. Here, we show that B. glandula produces a 199.6-kDa glycoprotein (named "MULTIFUNCin"), and following secretion, a 390-kDa homodimer in its native state. MULTIFUNCin expression is localized in the epidermis, cuticle, and new shell material. Consequently, this molecule can specify upon contact the immediate presence of a live barnacle. Shared, conserved domains place MULTIFUNCin in the alpha2 macroglobulin (A2M) subgroup of the thioester-containing protein family. Although previously undescribed, MULTIFUNCin shares 78% nucleotide sequence homology with a settlement-inducing pheromone (SIP) of the barnacle, Amphibalanus amphitrite Based on this and further evidence, we propose that the two proteins are orthologues and evolved ancestrally in structural and immunological roles. More recently, they became exploited as chemical cues for con- and heterospecific organisms, alike. MULTIFUNCin and SIP both induce habitat selection (settlement) by conspecific barnacle larvae. In addition, MULTIFUNCin acts as a potent feeding stimulant to major barnacle predators (sea stars and several whelk species). Promoting immigration via settlement on the one hand, and death via predation on the other, MULTIFUNCin simultaneously mediates opposing demographic processes toward structuring both predator and prey populations. As a multifunctional protein cue, MULTIFUNCin provides valuable sensory information, conveys different messages to different species, and drives complex biotic interactions. PMID- 27371386 TI - Ontogeny of Feeding Mechanics in Smoothhound Sharks: Morphology and Cartilage Stiffness. AB - The diet of dusky smoothhound sharks, Mustelus canis, shifts over ontogeny from soft foods to a diet dominated by crabs. This may be accompanied by changes in the skeletal system that facilitates the capture and processing of large and bulky prey. The hyoid arch, for example, braces the jaws against the cranium, and generates suction for prey capture and intraoral transport. In this study, ontogenetic changes in the hyoid arch were investigated by quantifying size, mineralization, and stiffness to determine whether increasingly stiffer cartilages are associated with the dietary switch. Total length and length of the hyomandibula and ceratohyal cartilages over ontogeny were the proxy for body size. Cross-sectional area, percent mineralization, and second moment of area were quantified in 28 individuals spanning most of the natural size range. Mechanical compression tests were conducted to compare flexural stiffness to size. Our results show that the morphological characters tested for the hyomandibular and ceratohyal cartilages scales isometrically with length. While stiffness of the hyomandibular and ceratohyal cartilages scales isometrically with length when assessed on morphological characters alone (second moment of area), this relationship becomes allometric when mechanical properties are included (flexural stiffness). Thus, while the hyoid arch elements grow isometrically, the mechanical properties dictate a scaling relationship that dwarfs morphological characteristics. The various combinations of morphologies and ontogenetic trajectories of chondrichthyan species illustrate the tremendous flexibility that they possess in the functional organization of the feeding apparatus. PMID- 27371388 TI - Urban-Rural Differences in Eye, Bill, and Skull Allometry in House Finches (Haemorhous mexicanus). AB - Allometry, the proportional scaling of log trait size with log body size, evolves to optimize allocation to growth of separate structures and is a major constraint on the functional limits of animal traits. While there are many studies demonstrating the rigidity of allometry across traits and taxa, comparatively less work has been done on allometric variation across environments within species. Rapidly changing environments, such as cities, may be prime systems for studying the flexibility of allometry because they uniquely alter many environmental parameters (e.g., habitat, light, noise). We studied size variation, allometry, and allometric dispersion of craniofacial traits in both sexes of urban and rural house finches (Haemorhous mexicanus) because many traits in the head are ecologically critical to the survival and acclimation of birds to their environment (e.g., brain: response to cognitive challenges; bill: foraging modes). We found that urban finches had shorter eye axial lengths and skull widths, but longer (but not wider or deeper) bills, than rural finches. Also, allometric slopes of eye, skull, and bill traits differed based on sex and environment. In the rural environment, females had a far steeper allometric slope for eye axial length than males, but such slopes were similar between males and females in the city. Skull allometry was similar for males and females in both environments, but urban birds had a shallower slope for skull length (but not width) than rural birds. Other traits only differed by sex (males had a steeper slope for bill width), and one trait did not differ based on either sex or environment (bill depth). The dispersion of points around the allometric line did not differ by sex or environment for any craniofacial variable. Due to the significant but low genetic divergence between urban and rural finch populations, allometric differences are probably largely driven by plastic forces. We suggest that differences in diet and cognitive demand of urban environments may drive these allometric patterns. Overall, these results indicate that allometry may shift due to rapid environmental change and differentially so between the sexes. PMID- 27371387 TI - The Metronome of Symbiosis: Interactions Between Microbes and the Host Circadian Clock. AB - The entrainment of circadian rhythms, physiological cycles with a period of about 24 h, is regulated by a variety of mechanisms, including nonvisual photoreception. While circadian rhythms have been shown to be integral to many processes in multicellular organisms, including immune regulation, the effect of circadian rhythms on symbiosis, or host-microbe interactions, has only recently begun to be studied. This review summarizes recent work in the interactions of both pathogenic and mutualistic associations with host and symbiont circadian rhythms, focusing specifically on three mutualistic systems in which this phenomenon has been best studied. One important theme taken from these studies is the fact that mutualisms are profoundly affected by the circadian rhythms of the host, but that the microbial symbionts in these associations can, in turn, manipulate host rhythms. The interplay between circadian rhythms and symbiosis is a promising new field with effects that should be kept in mind when designing future studies across biology. PMID- 27371389 TI - Small Packages, Big Returns: Uncovering the Venom Diversity of Small Invertebrate Conoidean Snails. AB - Venomous organisms used in research were historically chosen based on size and availability. This opportunity-driven strategy created a species bias in which snakes, scorpions, and spiders became the primary subjects of venom research. Increasing technological advancements have enabled interdisciplinary studies using genomics, transcriptomics, and proteomics to expand venom investigation to animals that produce small amounts of venom or lack traditional venom producing organs. One group of non-traditional venomous organisms that have benefitted from the rise of -omic technologies is the Conoideans. The Conoidean superfamily of venomous marine snails includes, the Terebridae, Turridae (s.l), and Conidae. Conoidea venom is used for both predation and defense, and therefore under strong selection pressures. The need for conoidean venom peptides to be potent and specific to their molecular targets has made them important tools for investigating cellular physiology and bioactive compounds that are beneficial to improving human health. A convincing case for the potential of Conoidean venom is made with the first commercially available conoidean venom peptide drug Ziconotide (Prialt(r)), an analgesic derived from Conus magus venom that is used to treat chronic pain in HIV and cancer patients. Investigation of conoidean venom using -omics technology provides significant insights into predator-driven diversification in biodiversity and identifies novel compounds for manipulating cellular communication, especially as it pertains to disease and disorders. PMID- 27371390 TI - Pre and Post-copulatory Selection Favor Similar Genital Phenotypes in the Male Broad Horned Beetle. AB - Sexual selection can operate before and after copulation and the same or different trait(s) can be targeted during these episodes of selection. The direction and form of sexual selection imposed on characters prior to mating has been relatively well described, but the same is not true after copulation. In general, when male-male competition and female choice favor the same traits then there is the expectation of reinforcing selection on male sexual traits that improve competitiveness before and after copulation. However, when male-male competition overrides pre-copulatory choice then the opposite could be true. With respect to studies of selection on genitalia there is good evidence that male genital morphology influences mating and fertilization success. However, whether genital morphology affects reproductive success in more than one context (i.e., mating versus fertilization success) is largely unknown. Here we use multivariate analysis to estimate linear and nonlinear selection on male body size and genital morphology in the flour beetle Gnatocerus cornutus, simulated in a non competitive (i.e., monogamous) setting. This analysis estimates the form of selection on multiple traits and typically, linear (directional) selection is easiest to detect, while nonlinear selection is more complex and can be stabilizing, disruptive, or correlational. We find that mating generates stabilizing selection on male body size and genitalia, and fertilization causes a blend of directional and stabilizing selection. Differences in the form of selection across these bouts of selection result from a significant alteration of nonlinear selection on body size and a marginally significant difference in nonlinear selection on a component of genital shape. This suggests that both bouts of selection favor similar genital phenotypes, whereas the strong stabilizing selection imposed on male body size during mate acquisition is weak during fertilization. PMID- 27371391 TI - All Features Great and Small-the Potential Roles of the Baculum and Penile Spines in Mammals. AB - Mammalian penises are morphologically diverse, including a highly variable and taxonomically informative baculum (os penis), and variable penile spines, both of which are possessed by many-but not all-species. To understand the evolution of genital morphologies, as well as the potential role of both the baculum, and penile spines that directly interact with female reproductive tract, we undertook a comparative study of male penile spines and their relationship with the baculum across all mammalian orders. Specifically, we investigated several factors that may explain the presence or absence of penile spines in mammals, including mating system, risk of sperm competition, female reproductive physiology, presence and width of the baculum, and phylogenetic history. We observed that the presence of both the baculum and penile spines is correlated with residual testes size, suggesting a potential role in sexual selection for these traits. We found no association between the presence of spines and mating system, or with the presence/width of the baculum, although relative testes mass was marginally associated with baculum width. We found no relationship between baculum presence or width and mating system. We also noted that spines presence or absence have an order-level distribution, and clear phylogenetic patterns of distribution across mammals. It is likely that spine morphology and distribution, not just presence, play an important role in genital evolution in mammals, but these features are poorly described in most groups. Quantitative data collection in most mammalian taxa would be useful to further elucidate the evolution of the complex genital morphology of this group. PMID- 27371392 TI - How to Make a Bird Skull: Major Transitions in the Evolution of the Avian Cranium, Paedomorphosis, and the Beak as a Surrogate Hand. AB - The avian skull is distinctive in its construction and in its function. Much of bird anatomical variety is expressed in the beak; but the beak itself, largely formed of the premaxillary bone, is set upon a shortened face and a bulbous, enlarged braincase. Here, we use original anatomical observations and reconstructions to describe the overall form of the avian skull in a larger context and to provide a general account of the evolutionary transformation from the early dinosaur skull-the skull of an archosaurian macropredator-to that of modern birds. Facial shortening, the enlargement of the braincase around an enlarged brain (with consequential reduction of circumorbital elements and the adductor chamber), and general thinning and looser articulation of bones are trends. Many of these owe to juvenilization or paedomorphosis, something that is abundantly evident from comparison of a juvenile early theropod (Coelophysis) to early avialans like Archaeopteryx Near the avian crown, the premaxilla becomes dramatically enlarged and integrated into the characteristic mobile kinetic system of birds. We posit that this addition of a large element onto the skull may be biomechanically feasible only because of the paedomorphic shortening of the face; and kinesis of the beak only because of the paedomorphic thinning of the bones and loosening of articulations, as played out in reverse during the maturation of Coelophysis Finally, the beak itself becomes elaborated as the hands are integrated into the wing. There are structural, kinematic, and neurological similarities between avian pecking and primate grasping. The ability to precision-select high-quality food against a complex but depauperate background may have permitted crown birds to survive the end-Cretaceous cataclysm by feeding on insects, seeds, and other detritus after the collapse of higher trophic levels in the food web. PMID- 27371393 TI - Re-evaluating the Role of Intrinsically Photosensitive Retinal Ganglion Cells: New Roles in Image-Forming Functions. AB - Recently, researchers identified a novel ganglion cell photoreceptor in vertebrates, called intrinsically photosensitive retinal ganglion cells (ipRGCs). These ipRGCs are photosensitive due to expression of a photopigment, melanopsin. Although ipRGCs were initially thought to be a uniform population of cells involved solely in subconscious, non-image forming behaviors, recent research points to a role for ipRGCs in pattern vision. Here we highlight the emerging evidence for this influence of ipRGCs on pattern vision and discuss important future directions for understanding this newly appreciated contribution of melanopsin signaling to visual processing. PMID- 27371394 TI - Lecithin and PLGA-based self-assembled nanocomposite, Lecithmer: preparation, characterization, and pharmacokinetic/pharmacodynamic evaluation. AB - The present study investigates the drug delivery potential of polymer lipid hybrid nanocomposites (Lecithmer(r)) composed of poly(D,L-lactide-co-glycolide (PLGA) and soya lecithin. Core-shell structure of Lecithmer was evident from cryo TEM images. Daunorubicin (DNR) and lornoxicam (LNX)-incorporated Lecithmer nanocomposites were evaluated for anticancer and anti-inflammatory activity. DNR- and LNX-loaded Lecithmer had mean particle size of ~335 and ~282.7 nm, respectively. Lecithmer formulated with different cationic lipids resulted in lower particle size (~120 nm) and positive zeta potential. Entrapment efficiency of DNR and LNX was 93.16 and 88.59 %, respectively. In vitro release of DNR from Lecithmer was slower compared to PLGA nanoparticles. DNR release from Lecithmer was significantly higher at pH 5.5 (80.96 %) as compared to pH 7.4 (55.95 %), providing advantage for selective tumor therapy. Similarly, sustained release of LNX (30 % in 10 h) was observed at pH 7.4. DNR in Lecithmer showed superior cytotoxicity on human erythroleukemic K562 cells. Pharmacokinetic study in Wistar rats with i.v. administered DNR-loaded Lecithmer showed higher volume of distribution, lower elimination rate constant, and longer half-life (81.68 L, 0.3535 h(-1), 1.96 h) as compared to DNR solution (57.46 L, 0.4237 h(-1), 1.635 h). Pharmacodynamic evaluation of orally administered LNX-loaded Lecithmer showed superior anti-inflammatory activity with maximum inhibition of 81.2 % vis-a-vis 53.57 % in case of LNX suspension. In light of these results, Lecithmer can be envisaged as a promising nanosystem for parenteral as well as oral drug delivery. PMID- 27371395 TI - Ex vivo investigation of ocular tissue distribution following intravitreal administration of connexin43 mimetic peptide using the microdialysis technique and LC-MS/MS. AB - This study aimed to develop and evaluate an ex vivo eye model for intravitreal drug sampling and tissue distribution of connexin43 mimetic peptide (Cx43MP) following intravitreal injection using the microdialysis technique and LC-MS/MS. An LC-MS/MS method was developed, validated, and applied for quantification of Cx43MP in ocular tissues. Microdialysis probes were calibrated for in vitro recovery studies. Bovine eyes were fixed in a customized eye holder and after intravitreal injection of Cx43MP, microdialysis probes were implanted in the vitreous body. Vitreous samples were collected at particular time intervals over 24 h. Moreover, 24 and 48 h after intravitreal injection ocular tissues were collected, processed, and analyzed for Cx43MP concentrations using LC-MS/MS. The LC-MS/MS method showed good linearity (r 2 = 0.9991). The mean percent recovery for lower (LQC), medium (MQC), and higher quality control (HQC) (0.244, 3.906, and 125 MUg/mL) was found to be 83.83, 84.92, and 94.52, respectively, with accuracy ranges between 96 and 99 % and limits of detection (LOD) and quantification (LOQ) of 0.122 and 0.412 MUg/mL. The in vitro recovery of the probes was found to be over 80 %. As per microdialysis sample analysis, the Cx43MP concentration was found to increase slowly in the vitreous body up to 16 h and thereafter declined. After 48 h, the Cx43MP concentration was higher in vitreous, cornea, and retina compared to lens, iris, and aqueous humor. This ex vivo model may therefore be a useful tool to investigate intravitreal kinetics and ocular disposition of therapeutic molecules after intravitreal injection. PMID- 27371397 TI - [Not Available]. PMID- 27371396 TI - [Not Available]. PMID- 27371398 TI - [Not Available]. PMID- 27371400 TI - [Not Available]. PMID- 27371399 TI - [Not Available]. PMID- 27371401 TI - [Not Available]. PMID- 27371402 TI - [Not Available]. PMID- 27371404 TI - [Not Available]. PMID- 27371403 TI - [Not Available]. PMID- 27371405 TI - [Not Available]. PMID- 27371406 TI - [Not Available]. PMID- 27371407 TI - [Not Available]. PMID- 27371408 TI - [Not Available]. PMID- 27371409 TI - [Not Available]. PMID- 27371410 TI - A clinically relevant dose of cyclophosphamide chemotherapy impairs memory performance on the delayed spatial alternation task that is sustained over time as mice age. AB - BACKGROUND: Cyclophosphamide chemotherapy is a mainstay of adjuvant breast cancer treatment. Unfortunately, this drug is associated with cognitive impairments in cancer patients that may accelerate cognitive aging. Memory is particularly affected in many patients. In order to better understand the precise cognitive impairments caused by this chemotherapy agent, we investigated a clinically relevant dose and administration paradigm on delayed spatial memory abilities in C57BL/6 mice. We utilized a delayed alternation paradigm similar to a delayed match to sample paradigm reported to be sensitive in human neurotoxicology research. METHODS: A dose of 200mg/kg cyclophosphamide was administered intravenously (at weekly intervals) for 4 weeks to C57BL/6 mice starting at 6 1/2 months of age. Memory was tested in mice using a reward-based delayed spatial alternation paradigm with delay values of 1.5, 3, 6.1, 12.4 and 25s presented randomly over 80 sessions (16 reinforcers per session), and testing began at the initiation of chemotherapy through 3 months. RESULTS: At the longest delay, i.e., that requiring the greatest memory, mice treated with chemotherapy exhibited a significant decline over time in percent correct which leveled off compared to controls that continued to improve slightly. CONCLUSIONS: Our clinically relevant model shows cyclophosphamide chemotherapy causes a slight decline in delayed spatial memories at the longest delay that is sustained over time as mice age. PMID- 27371411 TI - Atrial mapping during pulmonary vein pacing: a novel maneuver to detect and close residual conduction gaps in an ablation line. AB - BACKGROUND: Location of residual conduction gaps on ablation lines around pulmonary veins (PV) is challenging, and several maneuvers have been described. Atrial mapping during PV pacing-the "pace and map" maneuver-could localize gaps. METHODS AND RESULTS: We prospectively studied 209 patients undergoing PV isolation at a single institution over a 25-month period. In 24 (11.4 %) patients, 26 PV remained connected after an ablation line and an initial conventional gap closure protocol. The atrial side of the ablation line was mapped with the ablation catheter during PV pacing, and the earliest site was considered a gap site. Ablation at these gap sites resulted in bidirectional PV conduction block in 22 PV (85 %) in 21 patients (88 %), after 2.2 +/- 1.6 radiofrequency applications and 8.2 +/- 4.8 min. Early PV reconnection (>=20 min) occurred in 0 PV (0 %). During a mean follow-up of 12 +/- 6 months, eight patients (33 %) had arrhythmia recurrences. CONCLUSIONS: The "pace and map" maneuver is a relatively simple and efficacious means to identify gaps in ablation lines around PV, focusing on the atrial rather than the PV side of the line. It could be considered among the ways to eliminate residual conduction gaps. PMID- 27371412 TI - Normal Sinus Rhythm-Sinus Bradycardia is Common in Young Children Post extracardiac Fontan. AB - We hypothesized that normal sinus rhythm-sinus bradycardia is common in young children following extracardiac Fontan. After excluding patients with sinus pauses, junctional rhythm, tachy-brady syndrome, frequent ectopics, or ectopic atrial rhythm, we found an ambulatory 24-h Holter monitor average heart rate of 78 +/- 12 beats per minute (bpm) in 33 post-extracardiac Fontan children with a median age of 6 years (5-10). A 24-h average heart rate of 78 +/- 12 bpm is statistically significantly lower than a 24-h average heart rate value of 90 +/- 10 bpm derived from a similarly aged control population (p < 0.01). We conclude that after excluding those with significant arrhythmias, normal sinus rhythm sinus bradycardia is common in children post-extracardiac Fontan. PMID- 27371413 TI - Predictors of Change in Functional Health Status in Adults with Repaired Tetralogy of Fallot. AB - Left ventricular (LV) ejection fraction (EF) and right ventricular (RV) ejection fraction by cardiovascular magnetic resonance (CMR) are associated with functional health status in patients with repaired tetralogy of Fallot (TOF) in cross-sectional studies, but few longitudinal data are available. This study aimed to determine predictors of subsequent decrease in functional health status in midterm follow-up. Patients with repaired TOF who had previously completed CMR and assessment with the Short Form 36 version 2 (SF-36) were recruited for repeat CMR, SF-36, and exercise test, if they had not had interval pulmonary valve replacement (PVR). Patients from the same cohort who had undergone PVR were recruited for repeat SF-36. A total of 19 patients (median 33.5 years old, interquartile range [IQR] 26-42 years, 53 % male) had not undergone PVR and were enrolled at a median of 5.0 years (IQR 4.8-5.3) since prior CMR and SF-36. LVEF and RVEF did not change from baseline, while RV end-diastolic volume increased (138 +/- 34 vs. 126 +/- 31 ml/m(2), p = 0.02). In the overall cohort, SF-36 scores remained stable. However, higher baseline RV end-systolic volume and pulmonary regurgitant fraction correlated with subsequent decreases in SF-36 scores. In 9 patients post-PVR (median 35.9 years old, IQR 24-43), physical functioning increased compared to those without PVR (change in z-score +0.59 +/- 0.59 vs. -0.26 +/- 0.72, p = 0.005). In adults with repaired TOF who do not undergo PVR, LVEF, RVEF, and functional health status remain stable in midterm follow-up. However, baseline RV end-systolic volume correlates with subsequent change in functional health status, underscoring its importance in prognostication and timing of intervention in this population. PMID- 27371414 TI - [Not Available]. PMID- 27371416 TI - [Not Available]. PMID- 27371415 TI - [Not Available]. PMID- 27371417 TI - [Not Available]. PMID- 27371418 TI - [Not Available]. PMID- 27371419 TI - [Not Available]. PMID- 27371420 TI - [Not Available]. PMID- 27371421 TI - [Not Available]. PMID- 27371422 TI - [Not Available]. PMID- 27371423 TI - [Not Available]. PMID- 27371424 TI - [Not Available]. PMID- 27371425 TI - [Not Available]. PMID- 27371426 TI - [Not Available]. PMID- 27371427 TI - [Not Available]. PMID- 27371429 TI - [LDL-cholesterol targets arrive at the American guidelines]. PMID- 27371428 TI - Effects of repetitive photodynamic therapy using indocyanine green for acne vulgaris. AB - BACKGROUND: Indocyanine green (ICG) is a photosensitizer recently introduced for the treatment of acne. OBJECTIVE: To evaluate the efficacy and safety of photodynamic therapy (PDT) using ICG in subjects with acne vulgaris and to evaluate whether there was a difference in the efficacy of ICG-PDT between different numbers of treatment. MATERIALS AND METHODS: Subjects with acne on the face were included. ICG lotion (0.1%) was applied for 30 minutes, and a long pulse diode laser was used. Three or five treatments per subject were performed over 2 weeks. Acne lesion counts and Leeds revised acne grades were evaluated at baseline and 2 weeks after the last treatment. RESULTS: In total, 47 subjects completed the study. After both three and five ICG-PDT sessions, a significant reduction in acne lesions and significant improvement in Leeds revised acne grades were found in all treated subjects compared to baseline. In the subjects receiving five ICG-PDT sessions, the reduction of papules/pustules was greater than in the subjects receiving three ICG-PDT sessions (P < 0.01, respectively). However, there was no significant change in the count of nodules/cysts, although it is a negative trend (P = 0.066). Adverse effects were minimal. CONCLUSION: ICG PDT using long-pulsed diode laser can be a safe and effective tool for acne vulgaris. Moreover, repetitive treatments of five can cause further improvement of inflammatory acne lesions. PMID- 27371430 TI - [A retrospective, observational and multicentre study on patients with hyperactive bladder on treatment with mirabegron and oxybutinine under usual clinical practice conditions]. AB - OBJECTIVE: To evaluate therapeutic persistence, healthcare resources, medical costs and adverse events of oxybutynin and mirabegron treatments in patients with overactive bladder in routine medical practice. PATIENTS AND METHODS: An observational, retrospective, multicentre study was carried out using the records of patients attended to in 3 different geographic locations (Barcelona, Girona, Asturias). An analysis was made on the 2 study groups (oxybutynin and mirabegron). Follow-up time was one year. Persistence was defined as the time (months), without discontinuation of the initial treatment, or without change of treatment at least 60 days after the initial prescription. Primary endpoints: comorbidity, healthcare resources used, and adverse events. The data was analysed using the SPSSWIN Program, with a significance of P<.05. RESULTS: Of the total of1,277 patients included in the study, 42.9% were on oxybutynin and 57.1% mirabegron. The mean age was 69.3 years and 53.2% were female. Demographic characteristics and morbidity were similar between the drugs and had a similar persistence (35.0% oxybutynin vs. 32.2% mirabegron, P=.294), although their costs were lower (1,151.2 vs. ?1,809.6, P<.001). The biggest differences were observed in the price of medication (279.2 vs. ?692.3, P<.001; a variation of: -?413.1); and adverse events (9.7 vs. 4.9%, P<.001). CONCLUSIONS: Patients treated with oxybutynin vs. mirabegron for overactive bladder had similar persistence with the treatment, lower healthcare costs, but with higher oxybutynin vs. mirabegron adverse reaction rates. PMID- 27371431 TI - [Not Available]. PMID- 27371432 TI - [Not Available]. PMID- 27371433 TI - [Not Available]. PMID- 27371434 TI - [Not Available]. PMID- 27371435 TI - [Not Available]. PMID- 27371436 TI - [Not Available]. PMID- 27371437 TI - [Not Available]. PMID- 27371438 TI - [Not Available]. PMID- 27371439 TI - [Not Available]. PMID- 27371440 TI - [Not Available]. PMID- 27371442 TI - [Not Available]. PMID- 27371441 TI - [Not Available]. PMID- 27371443 TI - [Not Available]. PMID- 27371444 TI - [Not Available]. PMID- 27371445 TI - [Not Available]. PMID- 27371446 TI - [Not Available]. PMID- 27371447 TI - Research participants' skills development as HIV prevention peer educators in their communities. AB - This article describes the influence of a peer education programme on skills development among 22 women participating in HIV prevention trials. Interviews were used to collect data on peer educator experiences and their opinions of the trainings. The training enhanced their agency and confidence to engage their family and community on health promotion, including HIV prevention research procedures, thus improving their self-esteem and communication skills. Training and partnering with clinical trial participants as peer educators is an effective and sustainable community-based approach for HIV prevention. PMID- 27371448 TI - Laser biostimulation of wound healing: bioimpedance measurements support histology. AB - Laser biostimulation in medicine has become widespread supporting the idea of therapeutic effects of photobiomodulation in biological tissues. The aim of this study was to investigate the biostimulation effect of laser irradiation on healing of cutaneous skin wounds, in vivo, by means of bioimpedance measurements and histological examinations. Cutaneous skin wounds on rats were subjected to 635 nm diode laser irradiations at two energy densities of 1 and 3 J/cm2 separately. Changes in the electrical properties of the wound sites were examined with multi-frequency electrical impedance measurements performed on the 3rd, 7th, 10th, and 14th days following the wounding. Tissue samples were both morphologically and histologically examined to determine the relationship between electrical properties and structure of tissues during healing. Laser irradiations of both energy densities stimulated the wound healing process. In particular, laser irradiation of lower energy density had more evidence especially for the first days of healing process. On the 7th day of healing, 3 J/cm2 laser irradiated tissues had significantly smaller wound areas compared to non irradiated wounds (p < 0.05). The electrical impedance results supported the idea of laser biostimulation on healing of cutaneous skin wounds. Thus, bioimpedance measurements may be considered as a non-invasive supplementary method for following the healing process of laser-irradiated tissues. PMID- 27371451 TI - [Not Available]. PMID- 27371449 TI - What is the best moment to apply phototherapy when associated to a strength training program? A randomized, double-blinded, placebo-controlled trial : Phototherapy in association to strength training. AB - The effects of phototherapy (or photobiomodulation therapy) with low-level laser therapy (LLLT) and/or light-emitting diodes (LEDs) on human performance improvement have been widely studied. Few studies have examined its effect on muscular training and no studies have explored the necessary moment of phototherapy irradiations (i.e., before and/or after training sessions). The aim of this study was to determine the optimal moment to apply phototherapy irradiation when used in association with strength training. Forty-eight male volunteers (age between 18 to 35 years old) completed all procedures in this study. Volunteers performed the strength training protocol where either a phototherapy and/or placebo before and/or after each training session was performed using cluster probes with four laser diodes of 905 nm, four LEDs of 875 nm, and four LEDs of 640 nm-manufactured by Multi Radiance MedicalTM. The training protocol duration was 12 weeks with assessments of peak torque reached in maximum voluntary contraction test (MVC), load in 1-repetition maximum test (1 RM) and thigh circumference (perimetry) at larger cross-sectional area (CSA) at baseline, 4 weeks, 8 weeks, and 12 weeks. Volunteers from group treated with phototherapy before and placebo after training sessions showed significant (p < 0.05) changes in MVC and 1-RM tests for both exercises (leg extension and leg press) when compared to other groups. With an apparent lack of side effects and safety due to no thermal damage to the tissue, we conclude that the application of phototherapy yields enhanced strength gains when it is applied before exercise. The application may have additional beneficial value in post-injury rehabilitation where strength improvements are needed. PMID- 27371450 TI - A novel method of facial rejuvenation using a 2940-nm erbium:YAG laser with spatially modulated ablation: a pilot study. AB - The objective of this study was to determine the efficacy and safety of a novel method of facial rejuvenation using a 2940-nm erbium:YAG laser with Spatially Modulated AblationTM. A pilot study was performed in 16 women with moderate to severe signs of facial aging relative to chronological age, who underwent two treatment sessions with an Er:YAG laser coupled to the RecoSMATM technology (Linline, Minsk, Belarus). The whole face was treated in all patients. Clinical efficacy, tolerance, adverse effects, complications, and histological changes due to the treatment were evaluated. Clinical photographs and biopsies were taken before treatment and 3 months after the second treatment session. All patients completed the study and presented no significant complications. Histological changes in the epidermis and dermis as a result of treatment were found. Fine lines, wrinkles, and overall facial aging improved significantly (p < 0.0001). The mean reduction of fine lines and wrinkles was 59 % (r = 40-75 %). The mean improvement of overall facial aging was 74 % (r = 55-90 %). After showing the patients the comparative photographs before and after treatment, 75 % of women stated that they were satisfied or very satisfied and would recommend the treatment. Preliminary results show an excellent safety/efficacy profile for this novel technology, which, based on observed results, can be considered to have advantages over other methods of facial rejuvenation with lasers. PMID- 27371453 TI - [Not Available]. PMID- 27371452 TI - [Not Available]. PMID- 27371454 TI - [Not Available]. PMID- 27371455 TI - [Not Available]. PMID- 27371456 TI - [Not Available]. PMID- 27371457 TI - [Not Available]. PMID- 27371458 TI - [Not Available]. PMID- 27371459 TI - [Not Available]. PMID- 27371460 TI - [Not Available]. PMID- 27371462 TI - [Not Available]. PMID- 27371461 TI - [Not Available]. PMID- 27371463 TI - [Not Available]. PMID- 27371464 TI - [Not Available]. PMID- 27371466 TI - [Not Available]. PMID- 27371465 TI - [Not Available]. PMID- 27371467 TI - [Not Available]. PMID- 27371468 TI - [Not Available]. PMID- 27371469 TI - [Not Available]. PMID- 27371470 TI - [Not Available]. PMID- 27371471 TI - [Not Available]. PMID- 27371472 TI - [Not Available]. PMID- 27371473 TI - [Not Available]. PMID- 27371474 TI - [Not Available]. PMID- 27371475 TI - [Not Available]. PMID- 27371476 TI - [Not Available]. PMID- 27371477 TI - [Not Available]. PMID- 27371478 TI - [Not Available]. PMID- 27371479 TI - [Not Available]. PMID- 27371480 TI - [Not Available]. PMID- 27371481 TI - [Not Available]. PMID- 27371482 TI - Age-Related Increases in Verbal Knowledge Are Not Associated With Word Finding Problems in the Cam-CAN Cohort: What You Know Won't Hurt You. AB - OBJECTIVE: We tested the claim that age-related increases in knowledge interfere with word retrieval, leading to word finding failures. We did this by relating a measure of crystallized intelligence to tip-of-the-tongue (TOT) states and picture naming accuracy. METHOD: Participants were from a large (N = 708), cross sectional (aged 18-88 years), population-based sample from the Cambridge Centre for Ageing and Neuroscience cohort (Cam-CAN; www.cam-can.com). They completed (a) the Spot-the-Word Test (STW), a measure of crystallized intelligence in which participants circled the real word in word/nonword pairs, (b) a TOT-inducing task, and (c) a picture naming task. RESULTS: Age and STW independently predicted TOTs, with higher TOTs for older adults and for participants with lower STW scores. Tests of a moderator model examining interactions between STW and age indicated that STW was a significant negative predictor of TOTs in younger adults, but with increasing age, the effect size gradually approached zero. Results using picture naming accuracy replicated these findings. DISCUSSION: These results do not support the hypothesis that lifelong knowledge acquisition leads to interference that causes an age-related increase in TOTs. Instead, crystallized intelligence supports successful word retrieval, although this relationship weakens across adulthood. PMID- 27371483 TI - Margaret McCartney: Optional disclosure of payments is pointless. PMID- 27371484 TI - Epilepsy and nonadherence: Did you take your medicine? PMID- 27371486 TI - A new biomarker classification system for AD, independent of cognition: Agnosticism is a start. PMID- 27371485 TI - The ARIC-PET amyloid imaging study: Brain amyloid differences by age, race, sex, and APOE. AB - OBJECTIVE: To evaluate differences in amyloid deposition in a community-based cohort without dementia by age, sex, race, education, and APOE epsilon4 allele status. METHODS: Recruited from the longitudinal Atherosclerosis Risk in Communities study, 329 participants without dementia, ages 67-88 years, were imaged using florbetapir PET at 3 US community sites (Washington County, Maryland; Forsyth County, North Carolina; and Jackson, Mississippi). Standardized uptake value ratios (SUVRs) were calculated; global cortical SUVR >1.2 was evaluated as the primary outcome. Age, race, sex, education level, and number of APOE epsilon4 alleles were evaluated in multivariable models including vascular risk factors, brain white matter hyperintensity and total intracranial volume, and cognitive status. RESULTS: A total of 141 of the participants (43%) were black. In multivariable models, odds of elevated SUVR was increased in participants with increasing age (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.01-2.65 per 10 years of age) and black race (OR 2.08, 95% CI 1.23-3.51) but did not differ by educational level. Each epsilon4 allele was associated with increased odds of elevated SUVR (OR 2.65, 95% CI 1.61-4.39). CONCLUSIONS: In this community-based cohort without dementia, florbetapir uptake is associated with older age and APOE genotype. Black race was associated with higher SUVR, after adjusting for demographics, vascular risk factors, cognitive status, white matter hyperintensity volume, and APOE genotype, with effect sizes nearing those seen for APOE epsilon4. Replication of these findings is needed in other cohorts, and reasons for and consequences of these observed differences by race warrant further study. PMID- 27371487 TI - Social disinhibition is a heritable subphenotype of tics in Tourette syndrome. AB - OBJECTIVE: To identify heritable symptom-based subtypes of Tourette syndrome (TS). METHODS: Forty-nine motor and phonic tics were examined in 3,494 individuals (1,191 TS probands and 2,303 first-degree relatives). Item-level exploratory factor and latent class analyses (LCA) were used to identify tic based subtypes. Heritabilities of the subtypes were estimated, and associations with clinical characteristics were examined. RESULTS: A 6-factor exploratory factor analysis model provided the best fit, which paralleled the somatotopic representation of the basal ganglia, distinguished simple from complex tics, and separated out socially disinhibited and compulsive tics. The 5-class LCA model best distinguished among the following groups: unaffected, simple tics, intermediate tics without social disinhibition, intermediate with social disinhibition, and high rates of all tic types. Across models, a phenotype characterized by high rates of social disinhibition emerged. This phenotype was associated with increased odds of comorbid psychiatric disorders, in particular, obsessive-compulsive disorder and attention-deficit/hyperactivity disorder, earlier age at TS onset, and increased tic severity. The heritability estimate for this phenotype based on the LCA was 0.53 (SE 0.08, p 1.7 * 10(-18)). CONCLUSIONS: Expanding on previous modeling approaches, a series of TS-related phenotypes, including one characterized by high rates of social disinhibition, were identified. These phenotypes were highly heritable and may reflect underlying biological networks more accurately than traditional diagnoses, thus potentially aiding future genetic, imaging, and treatment studies. PMID- 27371489 TI - Lifetime direct costs of stroke for indigenous patients adjusted for comorbidities. AB - OBJECTIVE: To estimate the lifetime health costs of stroke by comorbidity and indigenous status in Australia's Northern Territory (NT), where a large indigenous population resides. METHODS: Incidence-based cohort study using linked hospital, primary care, and Pharmaceutical Benefits Scheme data to estimate lifetime direct costs for hemorrhagic stroke (HS), ischemic stroke (IS) and undetermined stroke (UND). Inverse probability-weighted survival analysis was adapted to adjust for loss to follow-up. Log-linear modeling was used to analyze the net stroke costs and marginal comorbidity costs by indigenous status. RESULTS: Between 1992 and 2013, there were 3,733 patients admitted with stroke in the NT (74% were incident strokes, 38% indigenous, 56% male, 56% IS). In 2012/2013 Australian dollars, the estimated lifetime cost for an incident stroke in NT was $302,538 AUD ($207,218 USD) per patient. The net lifetime cost per non indigenous female HS patient aged <45 years without comorbidity (reference category) was $72,773 AUD ($49,844 USD); IS cost 54% and UND 9% more than HS (p < 0.01). Stroke cost was greater for indigenous patients (? 44%) and patients with renal disease (? 71%), coronary heart disease (? 44%), hypertension (? 30%), and diabetes (? 28%) in comparison with the reference category (all p < 0.01). Chronic obstructive pulmonary disease, atrial fibrillation, depression, and cancer were negatively associated with lifetime stroke costs. CONCLUSIONS: The costs of stroke for indigenous people and patients with different comorbidities are substantial and an integrated prevention strategy is needed. PMID- 27371488 TI - The clinical spectrum of Caspr2 antibody-associated disease. AB - OBJECTIVE: To report a large cohort of patients with antibodies against contactin associated protein-like 2 (Caspr2) and provide the clinical spectrum of this disorder. METHODS: Serum and CSF samples were assessed at 2 neuroimmunology centers in Barcelona and Rotterdam. Patients were included if Caspr2 antibodies were confirmed with 2 independent techniques, including brain immunohistochemistry and cell-based assay. Clinical information was obtained by the authors or provided by treating physicians after patients' informed consent. RESULTS: Median age at symptom onset was 66 years. Of 38 patients, 34 were male. Median time to nadir of disease was 4 months (in 30% >1 year). The most frequent syndromes included limbic encephalitis (42%) and Morvan syndrome (29%). Seventy seven percent of the patients had >=3 of the following symptoms: encephalopathy (cognitive deficits/seizures), cerebellar dysfunction, peripheral nervous system hyperexcitability, dysautonomia, insomnia, neuropathic pain, or weight loss. A tumor, mostly thymoma, occurred in 19% of the patients. Immunoglobulin G4 subclass antibodies were present in all patients; 63% also had immunoglobulin G1 antibodies. Treatment response occurred in 93% of the patients and 25% had clinical relapses. CONCLUSIONS: Caspr2 antibodies associate with a treatable disorder that predominantly affects elderly men. The resulting syndrome may vary among patients but it usually includes a set of well-established symptoms. Recognition of this spectrum of symptoms and consideration of the protracted clinical course are important for early diagnosis of this disorder. Prompt immunotherapy and tumor therapy (if needed) often result in improvement. PMID- 27371490 TI - Nonadherence to antiepileptic drugs in Germany: A retrospective, population-based study. AB - OBJECTIVE: To assess the effect of patient and drug characteristics on medication adherence in people with epilepsy (PWE) in a large cohort representative of the German population. METHODS: Information was obtained from the Disease Analyzer database that collects anonymous demographic and medical data from practice computer systems throughout Germany. From 2010 to 2013, adult PWE were retrospectively analyzed regarding demographic characteristics, comorbidities, and treatment with antiepileptic drugs (AED). Adherence was measured using the medication possession ratio (MPR). Individuals with an MPR <80% were classified as nonadherent. Multivariate regression models were applied to assess the association of different factors with adherence by calculating adjusted odds ratios (OR) with 95% confidence intervals. RESULTS: A total of 31,317 PWE were included. The mean MPR was 81.1% (SD 25.7%) with 64.7% of patients showing good adherence (MPR >80%). Patient-related factors associated with good adherence to AED treatment were West German residence (OR 1.23, p < 0.0001) and learning disability (OR 1.80, p < 0.0001). Adherence was higher in patients treated with new than old (OR 1.52, p < 0.0001) and branded than generic AED (OR 1.44, p < 0.0001). Among the most common AED, levetiracetam achieved best adherence (OR 2.85, p < 0.0001), valproate lowest. Two or more daily dosages reduced adherence (TID vs QD: OR 0.84, p = 0.005; BID vs QD: OR 0.86, p = 0.011). CONCLUSIONS: One third of PWE treated with AED in Germany showed poor adherence, which was related to demographic characteristics and drug properties. Administration of new, well tolerated drugs in simple dosage regimens improved AED compliance. PMID- 27371491 TI - Global disparities in stroke and why we should care. PMID- 27371492 TI - A race effect on amyloid deposition? PMID- 27371493 TI - Relation of genomic variants for Alzheimer disease dementia to common neuropathologies. AB - OBJECTIVE: To investigate the associations of previously reported Alzheimer disease (AD) dementia genomic variants with common neuropathologies. METHODS: This is a postmortem study including 1,017 autopsied participants from 2 clinicopathologic cohorts. Analyses focused on 22 genomic variants associated with AD dementia in large-scale case-control genome-wide association study (GWAS) meta-analyses. The neuropathologic traits of interest were a pathologic diagnosis of AD according to NIA-Reagan criteria, macroscopic and microscopic infarcts, Lewy bodies (LB), and hippocampal sclerosis. For each variant, multiple logistic regression was used to investigate its association with neuropathologic traits, adjusting for age, sex, and subpopulation structure. We also conducted power analyses to estimate the sample sizes required to detect genome-wide significance (p < 5 * 10(-8)) for pathologic AD for all variants. RESULTS: APOE epsilon4 allele was associated with greater odds of pathologic AD (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.67-5.46, p = 1.9 * 10(-13)), while epsilon2 allele was associated with lower odds of pathologic AD (OR 0.42, 95% CI 0.30-0.61, p = 3.1 * 10(-6)). Four additional genomic variants including rs6656401 (CR1), rs1476679 (ZCWPW1), rs35349669 (INPP5D), and rs17125944 (FERMT2) had p values less than 0.05. Remarkably, half of the previously reported AD dementia variants are not likely to be detected for association with pathologic AD with a sample size in excess of the largest GWAS meta-analyses of AD dementia. CONCLUSIONS: Many recently discovered genomic variants for AD dementia are not associated with the pathology of AD. Some genomic variants for AD dementia appear to be associated with other common neuropathologies. PMID- 27371495 TI - Comment: Dissecting the genetic architecture of Tourette syndrome into subphenotypes. PMID- 27371494 TI - A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. AB - Biomarkers have become an essential component of Alzheimer disease (AD) research and because of the pervasiveness of AD pathology in the elderly, the same biomarkers are used in cognitive aging research. A number of current issues suggest that an unbiased descriptive classification scheme for these biomarkers would be useful. We propose the "A/T/N" system in which 7 major AD biomarkers are divided into 3 binary categories based on the nature of the pathophysiology that each measures. "A" refers to the value of a beta-amyloid biomarker (amyloid PET or CSF Abeta42); "T," the value of a tau biomarker (CSF phospho tau, or tau PET); and "N," biomarkers of neurodegeneration or neuronal injury ([(18)F] fluorodeoxyglucose-PET, structural MRI, or CSF total tau). Each biomarker category is rated as positive or negative. An individual score might appear as A+/T+/N-, or A+/T-/N-, etc. The A/T/N system includes the new modality tau PET. It is agnostic to the temporal ordering of mechanisms underlying AD pathogenesis. It includes all individuals in any population regardless of the mix of biomarker findings and therefore is suited to population studies of cognitive aging. It does not specify disease labels and thus is not a diagnostic classification system. It is a descriptive system for categorizing multidomain biomarker findings at the individual person level in a format that is easy to understand and use. Given the present lack of consensus among AD specialists on terminology across the clinically normal to dementia spectrum, a biomarker classification scheme will have broadest acceptance if it is independent from any one clinically defined diagnostic scheme. PMID- 27371496 TI - Risperidone long-acting injectable in the treatment of treatment-resistant schizophrenia with dopamine supersensitivity psychosis: Results of a 2-year prospective study, including an additional 1-year follow-up. AB - Dopamine supersensitivity psychosis (DSP) resulting from antipsychotic treatment is related to treatment-resistant schizophrenia (TRS), and its treatment has not been established to date. Maintaining thoroughly stable occupancy of the dopamine D2 receptor by risperidone long-acting injectable (RLAI) is one strategy for treatment. In this study, RLAI was given as an adjunctive medication to oral antipsychotic(s), which were switched partially and gradually to RLAI in 108 treatment-resistant patients for an additional 1-year follow-up in a 2-year study, and to compare the effects in 72 patients with a DSP history (DSP group) and 36 patients without this history (NonDSP group). Although both groups showed significant improvements in the total Brief Psychotic Rating Scale (BPRS) score during the follow-up period, greater improvement was observed for the DSP group than the NonDSP group. High doses (> 850 mg chlorpromazine-dose combined of oral antipsychotics and RLAI) did not significantly change in both groups throughout the study period; however, extrapyramidal symptoms, including tardive dyskinesia, were significantly improved only in the patients with DSP. This study strongly suggested that the RLAI treatment, even with only partial switching, provides relief from refractory symptoms, particularly for patients with a history of DSP. CLINICAL TRIAL REGISTRATION: http://www.umin.ac.jp/:UMIN000008487. PMID- 27371497 TI - Mephedrone and 3,4-methylenedioxy-methamphetamine: Comparative psychobiological effects as reported by recreational polydrug users. AB - AIMS: The purpose of this study was to compare the effects of mephedrone and 3,4 methylenedioxy-methamphetamine (MDMA), as reported by young recreational polydrug users. METHODS: 152 MDMA users and 81 mephedrone users were recruited through snowballing on social network sites. They completed a standard online questionnaire for either mephedrone or MDMA. The questions covered the average amount taken per session, the longest duration of usage in the last 12-months, subjective effects while on-drug, and recovery effects in the days afterwards. RESULTS: Mephedrone users reported a significantly longer maximum session of use than MDMA users. Mephedrone users also reported a significantly greater average amount used per session. The majority of on-drug subjective ratings did not differ between drugs, with similar increases in entactogenic effects. Although mephedrone users did report significantly more frequent issues with sleeping, anger and anxiety. In relation to recovery, mephedrone users reported more frequent craving, nasal irritation, paranoia, and relationship difficulties. Mephedrone users also rated general recovery effects as more severe over the seven-day period following use, taking more days to feel normal. CONCLUSIONS: The acute effects of MDMA and mephedrone were broadly similar. However, the recovery period for mephedrone was more enduring, possibly due to the longer duration of acute session usage. PMID- 27371499 TI - A special issue on the DNA damage response and genomic instability. PMID- 27371500 TI - Frequency and predictors of bleeding events after 2nd generation drug-eluting stent implantation differ depending on time after implantation. AB - BACKGROUND: Antiplatelet therapy is required after drug-eluting stent (DES) implantation, but bleeding events occur unexpectedly. We aimed to assess whether bleeding event predictors after 2nd generation DES (2nd DES) implantation differed by time after implantation. METHODS: We studied 1912 consecutive patients who underwent successful 2nd DES implantation (70+/-10 years, 72% male). Bleeding events were recorded as early (<=1 year) and late (>1 year). Major bleeding events were defined as a composite of type 5, 3, and 2 bleeding in the Bleeding Academic Research Consortium criteria. Predictors were assessed using a Cox proportional hazard model. RESULTS: Bleeding event rates were 3.3%, 5.1%, and 6.7% at 1, 2, and 3 years, respectively, with the highest 1-year rate in year 1 (p<0.001). Cause and severity of bleeding events were similar between early and late bleeding events. Prior history of gastrointestinal bleeding, non-steroidal anti-inflammatory drug use, and triple antithrombotic therapy [adjusted risk ratio (RR): 3.68, 3.21, 4.57, respectively; p<0.01] were independent predictors of early bleeding events. Age >80 years and severe renal dysfunction (adjusted RR: 2.27, 2.02, respectively; p<0.01) were independent predictors of late bleeding events. Survival rate was significantly lower in patients with bleeding events compared with patients without bleeding events (82.4% vs 90.1%; p<0.001). CONCLUSION: Frequency and predictors of bleeding events after 2nd DES implantation differ by time after implantation. Treatment strategies corresponding to individual patients are required. PMID- 27371501 TI - Physiological responses to dyadic interactions are influenced by neurotypical adults' levels of autistic and empathy traits. AB - Autistic traits are distributed on a continuum that ranges from non-clinical to clinical condition. Atypical responses to social situations represent a core feature of the Autism Spectrum Disorders phenotype. Here, we hypothesize that atypical physiological responses to social stimuli may predict non-clinical autistic and empathy traits levels. We measured physiological responses (heart rate, facial temperature) of 40 adults (20F) while showing them 24 movies representing dyadic interactions. Autistic traits were assessed through Autism Quotient questionnaire (AQ), while empathy traits were measured using the Empathy Quotient questionnaire (EQ). Opposite correlations between AQ and EQ scores and physiological responses were found. Analysis of physiological responses revealed that individuals with better social abilities, low AQ and high EQ, show opposite activation patterns compared to people with high AQ and low EQ. Findings show that physiological responses could be biomarkers for people's autistic traits and social abilities. PMID- 27371498 TI - Antipsychotic-induced sensitization and tolerance: Behavioral characteristics, developmental impacts, and neurobiological mechanisms. AB - Antipsychotic sensitization and tolerance refer to the increased and decreased drug effects due to past drug use, respectively. Both effects reflect the long term impacts of antipsychotic treatment on the brain and result from the brain's adaptive response to the foreign property of the drug. In this review, clinical evidence of the behavioral aspect of antipsychotic sensitization and tolerance is selectively reviewed, followed by an overview of preclinical literature that examines these behavioral characteristics and the related pharmacological and nonpharmacological factors. Next, recent work on the developmental impacts of adolescent antipsychotic sensitization and tolerance is presented and recent research that delineates the neurobiological mechanisms of antipsychotic sensitization and tolerance is summarized. A theoretical framework based on "drug learning and memory" principles is proposed to account for the phenomena of antipsychotic sensitization and tolerance. It is maintained that antipsychotic sensitization and tolerance follow basic principles of learning or acquisition ("induction") and memory ("expression"). The induction and expression of both effects reflect the consequences of associative and nonassociative processing and are strongly influenced by various pharmacological, environmental, and behavioral factors. Drug-induced neuroplasticity, such as functional changes of striatal dopamine D2 and prefrontal serotonin (5-HT)2A receptors and their mediated signaling pathways, in principle, is responsible for antipsychotic sensitization and tolerance. Understanding the behavioral characteristics and neurobiological underpinnings of antipsychotic sensitization and tolerance has greatly enhanced our understanding of mechanisms of antipsychotic action, and may have important implications for future drug discovery and clinical practice. PMID- 27371502 TI - Effects of predator odour on antipredator responses of Nile tilapia. AB - Several fish species exhibit antipredator responses when exposed to chemicals which indicate risk of predation. One such substance is the scent of a predator (a kairomone) that may induce defensive responses in a potential prey. In the present study, we show that chemical cues (odour) from predator fish induce antipredator and stress responses in Nile tilapia. When exposed to predator odour, Nile tilapia decreased activity and increased ventilation rate (VR), but no increase in plasma levels of cortisol and glucose was found. Although the hypothalamic-pituitary-interrenal axis (HPI axis) was not activated, an increase in ventilation is a fast response which can provide the fish enough oxygen for a 'fight or flight' event when facing a predator. Thus, this respiratory response suggests an anticipated adjustment in order to prepare the body for a defensive response, such as escaping, irrespective of HPI axis activation. PMID- 27371504 TI - Young and early. PMID- 27371503 TI - 7, 8, 3'-Trihydroxyflavone Promotes Neurite Outgrowth and Protects Against Bupivacaine-Induced Neurotoxicity in Mouse Dorsal Root Ganglion Neurons. AB - BACKGROUND 7, 8, 3'-trihydroxyflavone (THF) is a novel pro-neuronal small molecule that acts as a TrkB agonist. In this study, we examined the effect of THF on promoting neuronal growth and protecting anesthetics-induced neurotoxicity in dorsal root ganglion (DRG) neurons in vitro. MATERIAL AND METHODS Neonatal mouse DRG neurons were cultured in vitro and treated with various concentrations of THF. The effect of THF on neuronal growth was investigated by neurite outgrowth assay and Western blot. In addition, the protective effects of THF on bupivacaine-induced neurotoxicity were investigated by apoptosis TUNEL assay, neurite outgrowth assay, and Western blot, respectively. RESULTS THF promoted neurite outgrowth of DRG neurons in dose-dependent manner, with an EC50 concentration of 67.4 nM. Western blot analysis showed THF activated TrkB signaling pathway by inducing TrkB phosphorylation. THF also rescued bupivacaine induced neurotoxicity by reducing apoptosis and protecting neurite retraction in DRG neurons. Furthermore, the protection of THF in bupivacaine-injured neurotoxicity was directly associated with TrkB phosphorylation in a concentration-dependent manner in DRG neurons. CONCLUSIONS THF has pro-neuronal effect on DRG neurons by promoting neurite growth and protecting against bupivacaine-induced neurotoxicity, likely through TrkB activation. PMID- 27371505 TI - Research and drug development activities in rare diseases: differences between Japan and Europe regarding influence of prevalence. AB - Orphan drug legislation has contributed enormously to promote drug development for rare diseases but further effective and sustainable approaches are required. This study focused on the difference of rare disease prevalence between Japan and Europe, classified the rare diseases comprehensively using cluster analysis and analyzed the influence of prevalence on research activity and drug development. Although overall strong correlative progress of research was found and absolute numbers of values were greater in Europe than in Japan, the regional higher prevalent diseases demonstrated more progress of research and development relatively in the region by examining clusters. Our findings suggest potential optimal drug development in consideration of regional differences. Moreover, an in-depth analysis of diseases that showed exceptional research achievements compared with prevalence speculated important determinants of progress. PMID- 27371506 TI - Cell spheroids: the new frontiers in in vitro models for cancer drug validation. AB - During the past decades, evaluation of anticancer drugs utilizing 2D cell cultures has been in common usage. In contrast to 2D cell cultures however, which lack many characteristics of the complex in vivo situation, 3D cell or tissue culture systems, such as cellular spheroids, better mimic the crucial tumor tissue properties and the microenvironment, and are thus more appropriate for the evaluation of pharmaceutical candidates. Taking the characteristics of the tumor microenvironment into consideration, crucial aspects and recent advances related to cell spheroids in the validation of anticancer drugs are discussed here. PMID- 27371507 TI - Enrichment and in vitro features of the putative gonocytes from cryopreserved testicular tissue of neonatal bulls. AB - Enrichment and propagation of gonocytes or spermatogonial stem cells (SSCs) from cryopreserved testicular tissue is essential to apply SSCs-related techniques in large domestic animals. We previously reported the cryopreservation of adult bovine testicular tissue. Here, we conducted the enrichment and culture of putative gonocytes from cryopreserved testicular tissues of post-natal 1-day-old bulls. The testicular structure was well maintained after freezing and thawing. Higher mRNA levels of gonocyte/SSCs markers (PLZF, GFRalpha1, and UCHL-1) than those of pluripotency genes (Oct4, Sox2, and Nanog) were detected in the frozen thawed sex cords. GFRalpha1 was specifically detected in the membrane and cytoplasm of gonocytes by immunostaining. Differential plating provided 40-50% enrichment of putative gonocytes. They were single, paired-, aligned-cells, or grape cluster-like colonies in minimum essential medium (MEM) containing 2.5% FBS + 2 mM glutamine + 100 IU/mL penicillin-streptomycin + 40 MUg/mL gentamycin + 15 mM HEPES + 10 mM beta-mercaptoethanol + 0.1 mM non-essential amino acids + 1 mM sodium pyruvate. On day 3, gonocyte progeny increased and the contaminated somatic cells spread and concurrently divided slowly. On day 5, gonocyte progeny proliferated continuously and typical intercellular bridges formed by incomplete cytokinesis in paired-cells or aligned-cysts were observed. Immunochemically, they were still GFRalpha1 and PLZF positive. These cells expressed significantly higher gonocyte/SSCs marker mRNAs than pluripotency gene mRNAs, concomitant with a higher level of differentiated spermatogonia marker c-kit. With time, gonocyte progeny colonies appeared in varied sizes and expanded dramatically on day 7. After cultured for 9-10 days, however, large colonies collapsed and dispersed as some single cells and small syncytial cysts. Together, MEM containing 10% dimethyl sulfoxide + 2.5% newborn calf serum provides efficient cryoprotection for the testicular tissue from 1-day-old neonatal bulls. Putative gonocytes enriched from these nascent tissues present robust proliferation capacity, conserved gonocyte/SSCs markers, and SSCs-like in vitro features. PMID- 27371508 TI - The Last 2000 Days: Thou shouldst not have been old till thou hadst been wise. Shakespeare (King Lear). AB - This essay is an exploration of an extended period of the last 2000 days of anticipated mortality from the perspective of an aging gerontologist. The last 2000 days come at the end of what has come to be referred to as the Third Age (Silva, L. R. (2008). [From old age to third age: The historical course of the identities linked to the process of ageing]. Historia, ciencias, saude Manguinhos, 15: , 155-168. doi:10.1590/S0104-59702008000100009). Life in the last 2000 days is a period in which the appreciation of finitude comes into new prominence, affecting a variety of elements that command attention-from individuals and from scholars. The significance of the last 2000 days is explored from two perspectives: First, the meaning, if any, of a more than half century career spent in gerontology on the personal experience of being old- how I think about my own old age, and second, an exploration of a variety of considerations that other older persons might be prompted to consider. The last 2000 days will be experienced in relatively good stages of "ability," activity, and potential engagement. This rumination explores the personal meaning of this penultimate life stage, pre-dying. It suggests some systematic consideration of what recognition of these days may mean-perception of time, identity and role, status, risks and vulnerabilities, dealing with disability, winding up/winding down/giving up, legacies, and, of course, death and dying. These issues are personal. There is no set value scale that suggests "successful aging" or "failed aging." PMID- 27371510 TI - Advanced Heart Failure: Prevalence, Natural History, and Prognosis. AB - Heart failure is a complex clinical syndrome. The natural history of this syndrome is progressive. Advanced heart failure is present when a patient has signs and symptoms of heart failure that are refractory to therapy. Patients with the most advanced disease and worst prognosis can be identified using iterative, integrated clinical assessment of symptom burden, effort intolerance, and cardiac dysfunction. Recognizing the transition to advanced heart failure is necessary for referral to an advanced heart disease program. Advanced heart disease specialists can tailor medical therapies, perform risk stratification, and evaluate candidacy for mechanical support, transplantation, or end-of-life palliative treatment options. PMID- 27371509 TI - Outbreak of hirame rhabdovirus infection in cultured spotted sea bass Lateolabrax maculatus on the western coast of Korea. AB - In this study, we determined the cause of a disease outbreak in spotted sea bass, Lateolabrax maculatus reared in culture cages on the western coast of Korea in 2013. The major signs in the diseased fish exhibited were haemorrhaging on the membranes of the abdomen, gastrointestinal organs and opercular gills, as well as an enlarged spleen. No external morphological signs of infection were visible, except for a darkening in colour. No parasites or pathological bacteria were isolated from the diseased fish; however, epithelioma papulosum cyprini (EPC) cells inoculated with tissue homogenates from the diseased fish showed cytopathic effects (CPEs). Virus particles in the EPC cells were bullet-shaped, 185-225 nm long and 70-80 nm wide, characteristic of Rhabdoviridae. Polymerase chain reaction analyses of homogenized tissues from the diseased fish and supernatants of cell cultures with CPEs indicated specific, 553-bp-long fragments corresponding to the matrix protein gene of the hirame rhabdovirus (HIRRV). Phylogenetically, the HIRRV phosphoprotein gene of spotted sea bass was more closely related to phosphoproteins from Chinese and Polish HIRRV strains than from other Korean strains. To our knowledge, this is the first report of HIRRV infection in cultured spotted sea bass. PMID- 27371511 TI - Cardiorenal Interactions. AB - Recently, there has been increased appreciation of the identification and management of comorbidities in heart failure patients, and for therapies targeting conventional heart failure signs and symptoms. Renal dysfunction is common in patients with heart failure and is associated with high morbidity and mortality. Early identification of renal damage through novel biomarkers and the use of new pharmacological strategies aimed at preserving renal function may represent an important objective in the treatment. This article reviews the epidemiology and pathophysiology of cardiorenal syndrome in heart failure, and highlights novel biomarkers and improved therapies targeting renal dysfunction. PMID- 27371512 TI - Cardiohepatic Interactions: Implications for Management in Advanced Heart Failure. AB - Liver disease is a common sequela of heart failure and can range from mild reversible liver injury to hepatic fibrosis and, in its most severe form, cardiac cirrhosis. Hepatic fibrosis and cirrhosis due to chronic heart failure have important implications for prognosis, medication management, mechanical circulatory support, and heart transplantation. This article reviews the current understanding of liver disease in heart failure and provides a framework for approaching liver disease in the advanced heart failure population. PMID- 27371513 TI - Frailty in Advanced Heart Failure. AB - Frailty is defined as a biological syndrome reflecting impaired physiologic reserve and heightened vulnerability to stressors. The evolving profile of heart failure (HF), increased survival of aging patients with complex comorbidities in parallel with the growing population undergoing mechanical circulatory support as lifetime therapy, means that advanced HF specialists are becoming aware of the burden of frailty and its downstream consequences on postintervention outcomes in these patients. The limited data available to date suggest that frailty is highly prevalent in patients with advanced HF and appears to provide prognostic information not captured by traditional risk assessment. PMID- 27371514 TI - Tailoring Therapies in Advanced Heart Failure. AB - Heart failure effects millions of people throughout the world and is a growing epidemic with a significant impact on the economics and systems of care delivery. The goal of therapy in advanced heart failure is to improve quality of life and prolong survival. Standard medical therapies may require tailoring as advanced therapies are considered in the context of patient and caregiver goals. The aim of this review is to summarize concepts for tailored medical therapy and monitoring in advanced heart failure and discuss the importance of tailoring systems of care and shared decision making in advanced heart failure. PMID- 27371515 TI - Temporary Percutaneous Mechanical Circulatory Support in Advanced Heart Failure. AB - Cardiogenic shock is severe, refractory heart failure caused by significant myocardial dysfunction in the setting of adequate preload that is accompanied by systemic hypoperfusion. Progressive end-organ dysfunction is a hallmark of persistent cardiogenic shock and necessitates intervention to overcome altered hemodynamics and restore end-organ perfusion. Temporary percutaneous mechanical circulatory support is an established modality in the treatment of cardiogenic shock and is increasingly used in patients with cardiogenic shock as a bridge to recovery or further definitive therapy. This article reviews the current devices, their effects on left ventricular hemodynamics, and the evidence supporting their continued use. PMID- 27371516 TI - Role of Durable Mechanical Circulatory Support for the Management of Advanced Heart Failure. AB - In the past decade, there has been a dramatic evolution in the field of mechanical circulatory support. Device-related complications continue to burden the field and will be a major obstacle for achieving therapeutic noninferiority compared with cardiac transplant. Selected patients with end-stage systolic heart failure enjoy an average survival of 80% at 1 year post-ventricular assist device implant, vastly better than survival rates of 25% to 50% on chronic inotrope support. Early patient referral to an advanced heart failure specialist before the onset of significant end-organ dysfunction and malnutrition is critical for achieving good operative outcomes. PMID- 27371517 TI - Changing Role of Heart Transplantation. AB - Heart transplantation has become standard of care for end-stage heart failure. Challenges include the limited supply of donor organs and the increased complexity of heart transplant candidates who are at higher risk for poor outcomes. Recent advances may address these challenges, including proposed changes in heart transplant allocation policy, a better understanding of the definition and management of primary graft dysfunction, and advances in the management of sensitized heart transplant candidates. Developments in these areas may result in more equitable distribution and expansion of the donor pool and improved quality of life and survival for heart transplant recipients. PMID- 27371518 TI - Cardiac Resynchronization Therapy and Implantable Cardioverter Defibrillator Therapy in Advanced Heart Failure. AB - Patients with advanced heart failure are at high risk for progression of their disease and sudden cardiac death. The role of device therapy in this patient population continues to evolve and is directed toward improving cardiac pump function and/or reducing sudden arrhythmic death. PMID- 27371519 TI - Home Inotropes and Other Palliative Care. AB - Heart failure is a leading case of morbidity and mortality worldwide, and patients with advanced heart failure have limited options without any available cure. These options mainly include cardiac transplantation or mechanical circulatory support device implantation. Chronic home inotropes are an option in these patients for a variety of indications. This report discusses the use of chronic home inotropes in palliated heart failure patients and reviews the role of palliative care management in end-stage heart failure. PMID- 27371520 TI - Recovery Versus Remission: Clinical Insights. AB - Adverse myocardial remodeling can be reversed by medical, surgical, and device therapies leading to reduced heart failure (HF) morbidity and mortality and significant improvements in the structure and function of the failing heart. The growing population of HF patients who experience a degree of myocardial improvement should be better studied in terms of long-term outcomes and underlying biology to more clearly define the difference between recovery and remission. These investigations should also be focused in determining whether in chronic HF patients complete myocardial recovery is achievable at a meaningful rate and help us better understand, predict, and manipulate cardiac recovery. PMID- 27371522 TI - Advanced Therapies for Advanced Heart Failure: Time to Raise Awareness. PMID- 27371521 TI - Novel Biological Therapies Targeting Heart Failure: Myocardial Rejuvenation. AB - Recovery of ventricular function occurs in a subset of patients with advanced heart failure treated with medical and/or mechanical therapy. Finding strategies that induce ventricular recovery through induction of repair, regeneration, or "rejuvenation" is a long-sought goal of research programs. Cell-based strategies, use of recombinant growth and survival factors, and gene delivery are under investigation. In this brief article we highlight a few of the biological approaches in development to treat heart failure. PMID- 27371523 TI - Drugs for treating alcohol dependence in England cost nearly L4m in 2014. PMID- 27371525 TI - Younger Dual-Eligibles Who Use Federally Qualified Health Centers Have More Preventable Emergency Department Visits, but Some Have Fewer Hospitalizations. AB - OBJECTIVE: To determine whether younger dual-eligibles receiving care at federally qualified health centers (FQHCs) have lower rates of ambulatory care sensitive (ACS) hospitalization and emergency department (ED) visits. DATA SOURCES: We used the 100% Medicare Part A and Part B institutional claims from 2007 to 2010 for dual-eligibles younger than 65 years, enrolled in traditional fee-for-service Medicare, who received care at an FQHC or lived in a primary care service area with an FQHC. METHODS: Our cross-sectional analysis used negative binomial regressions to model ACS hospitalizations and ED visits as a function of prior year FQHC use. The model adjusted for beneficiary age, gender, race, and chronic diseases, as well as county fixed effects, time trends, and race-FQHC use interactions. RESULTS: FQHC use is associated with a decrease in ACS hospitalization rates for whites (2.8 per 1000 persons), but an increase among blacks (2.5 per 1000 persons). FQHC use is also associated with an increase in ACS ED visits, from 27 to 33 more visits per 1000 persons per year, depending on patient race. CONCLUSIONS: ACS hospital use is higher for FQHC users than nonusers, but white FQHC users have fewer ACS hospitalizations. More research is needed to understand how this relationship varies within and between centers. PMID- 27371530 TI - The Relationship Between Religiosity and Deviance Among Adolescents in a Religiously Pluralistic Society. AB - Most empirical studies of religion and deviance have employed samples from Western countries, especially the United States, where one predominant religion Judeo-Christianity-is an embedded fixture of the mainstream culture. By comparison, research conducted in East Asia, where religious pluralism is the norm rather than the exception, is extremely scarce. Moreover, a large proportion of the population in East Asia professes themselves to be atheists. Given the drastically different religious climates between East and West, it thus remains an important empirical question whether the research findings on religiosity and deviance garnered from Western samples can be generalizable to East Asia. Given this background, the current study assesses the linkage between religiosity and deviance using a sample of adolescents in South Korea, where secular social controls emanating from Confucianism are potent. The results of the study show that religiosity's deviance-constraining effects are considerably weaker in South Korea. In addition, many of the Western findings do not apply to the South Korean context. PMID- 27371531 TI - Recidivism Patterns Among Two Types of Juvenile Homicide Offenders: A 30-Year Follow-Up Study. AB - Although juvenile homicide has been a matter of concern in the United States since the 1980s, prior research has not addressed long-term recidivism patterns for convicted juvenile murderers. Furthermore, a prominent juvenile homicide typology had not previously been tested with U.S. offenders. The present study examined whether juvenile offenders who killed or attempted to kill during the commission of a crime differed from those who killed due to some type of conflict on pre-incarceration, incarceration, and post-incarceration variables. These offenders were sentenced to adult prison in the early 1980s. Follow-up data spanned 30 years. The results indicated that approximately 88% of released offenders have been rearrested. Analyses of pre-incarceration variables revealed that crime-oriented offenders were significantly more likely to commit the homicide offense using accomplices than conflict-oriented offenders, and the latter were significantly more likely to use a firearm during the homicide incident. The circumstances of the homicide, however, were not significantly related to any other pre-incarceration variables, release from prison, number of post-release arrests, and number of post-release violent offenses. The implications of the findings, their comparability to previous follow-up research on this typology, and avenues for future research are discussed. PMID- 27371532 TI - Integrating acupuncture into primary health care: the experience of an educational model implemented within the Brazilian Unified Health System in Florianopolis. AB - OBJECTIVE: Primary health care (PHC) is the main entry point and the first level of contact for individuals, families and communities within the Brazilian public health system. Considering that few studies have investigated the use of acupuncture in PHC, this article presents our experience in the city of Florianopolis when integrating acupuncture into PHC using an educational programme developed to teach acupuncture to primary care physicians (PCPs). METHODS: The course programme was designed using the WHO standards for acupuncture training and discussed at three consensus meetings. Between 2011 and 2014 three iterations of an introductory acupuncture course for PCPs were offered. During this period 53 physicians finished the programme. RESULTS: The number of acupuncture sessions in PHC rose from 1349 in 2011 to 6488 in 2015. It was observed in 2015 that 81% of the course participants working in PHC were regularly using acupuncture in their daily practice, with a mean number of sessions of 11.35 sessions per month. Moreover, collaborative work, which started during the course between the PCPs and the acupuncture specialists in secondary and tertiary public health care, helped to increase the quality of acupuncture referrals and facilitate clinical case discussions. CONCLUSIONS: Our experience in the city of Florianopolis shows that teaching acupuncture to PCPs is a sustainable model that can help introduce acupuncture into PHC. Furthermore it can expand access to acupuncture treatment for the population and increase the communication between PCPs and acupuncture specialists. PMID- 27371533 TI - Ultrasonography in acupuncture: potential uses for education and research. PMID- 27371535 TI - Nearly half of people with infertility do not seek medical help, survey shows. PMID- 27371536 TI - The Veterinary Forensic Necropsy: A Review of Procedures and Protocols. AB - Investigation of animal-related crime, and therefore submission of forensic cases to veterinary pathology facilities, is increasing, yet many veterinary pathologists are unfamiliar and often uncomfortable with involvement in the forensic necropsy. This article discusses various aspects of the forensic necropsy without specific attention to any particular species group or crime. General advice is given on procedures, documentation, and recording of the examination, and the article indicates how these features may differ from those used in investigation of natural disease. It also discusses evidence management, including recordkeeping, identification of evidence, labeling of photographs, and use of standard operating procedures and protocols. Various written and visual methods for documentation of the forensic necropsy are covered, and adjunctive topics such as sample collection, assessment, and description of wounds and taphonomy are included. Cause, mechanism, and manner of death are defined, and guidance to the use of these terms is given. The aim of this article is to offer guidance on procedural aspects of the forensic necropsy that will help those developing their forensic services, contribute to standardization of the provision of forensic veterinary pathology, and build the confidence of the "uncomfortable" forensic veterinary pathologist. PMID- 27371534 TI - Hemidesmosome integrity protects the colon against colitis and colorectal cancer. AB - OBJECTIVE: Epidemiological and clinical data indicate that patients suffering from IBD with long-standing colitis display a higher risk to develop colorectal high-grade dysplasia. Whereas carcinoma invasion and metastasis rely on basement membrane (BM) disruption, experimental evidence is lacking regarding the potential contribution of epithelial cell/BM anchorage on inflammation onset and subsequent neoplastic transformation of inflammatory lesions. Herein, we analyse the role of the alpha6beta4 integrin receptor found in hemidesmosomes that attach intestinal epithelial cells (IECs) to the laminin-containing BM. DESIGN: We developed new mouse models inducing IEC-specific ablation of alpha6 integrin either during development (alpha6DeltaIEC) or in adults (alpha6DeltaIEC-TAM). RESULTS: Strikingly, all alpha6DeltaIEC mutant mice spontaneously developed long standing colitis, which degenerated overtime into infiltrating adenocarcinoma. The sequence of events leading to disease onset entails hemidesmosome disruption, BM detachment, IL-18 overproduction by IECs, hyperplasia and enhanced intestinal permeability. Likewise, IEC-specific ablation of alpha6 integrin induced in adult mice (alpha6DeltaIEC-TAM) resulted in fully penetrant colitis and tumour progression. Whereas broad-spectrum antibiotic treatment lowered tissue pathology and IL-1beta secretion from infiltrating myeloid cells, it failed to reduce Th1 and Th17 response. Interestingly, while the initial intestinal inflammation occurred independently of the adaptive immune system, tumourigenesis required B and T lymphocyte activation. CONCLUSIONS: We provide for the first time evidence that loss of IECs/BM interactions triggered by hemidesmosome disruption initiates the development of inflammatory lesions that progress into high-grade dysplasia and carcinoma. Colorectal neoplasia in our mouse models resemble that seen in patients with IBD, making them highly attractive for discovering more efficient therapies. PMID- 27371537 TI - Pathogenesis of Renal Lesions in Chickens After Experimental Infection With 9a5b Newcastle Disease Virus Mutant Isolate. AB - In this study, we investigated the pathogenesis of Newcastle disease virus (NDV) in the chicken kidney. Twenty-six 32-day-old specific pathogen-free chickens were intranasally inoculated with the 9a5b NDV mutant isolate. Kidney tissue samples, collected at 6 and 12 hours postinoculation (hpi) and 1, 2, 3, 5, and 10 days postinoculation (dpi), were analyzed by histopathology, immunohistochemistry (IHC), reverse transcription polymerase chain reaction (RT-PCR), and virus titration. Histopathologically, tubulointerstitial nephritis was detected in the renal cortex and predominantly in the medulla. Nephrotropism of 9a5b NDV was confirmed by IHC, RT-PCR, and virus isolation. Massive degenerative changes and infiltration of CD3-immunopositive cells accompanied replication of the 9a5b NDV isolate in chicken kidneys. In conclusion, pathological changes that were caused by NDV in chicken kidneys were similar to those caused by avian influenza virus, infectious bronchitis virus, and avian nephritis virus, and this highlights the importance of including NDV in the differential diagnosis of kidney disease in chickens. PMID- 27371539 TI - Perianesthetic Mortality in Domestic Animals: A Retrospective Study of Postmortem Lesions and Review of Autopsy Procedures. AB - Autopsy of animals that die in the perianesthetic period allows identification of anesthetic and surgical complications as well as preexisting disease conditions that may have contributed to mortality. In most studies to date investigating perianesthetic mortality in animals, inclusion of autopsy data is very limited. This retrospective study evaluated autopsy findings in 221 cases of perianesthetic death submitted to a veterinary diagnostic laboratory from primary care and referral hospitals. Canine (n = 105; 48%) and feline (n = 90; 41%) cases predominated in the study, involving elective (71%) and emergency (19%) procedures. The clinical history provided to the pathologist was considered incomplete in 42 of 221 cases (19%), but this history was considered essential for evaluating the circumstances of perianesthetic death. Disease had been recognized clinically in 69 of 221 animals (31%). Death occurred in the premedication or sedation (n = 19; 9%), induction (n = 22; 11%), or maintenance (n = 73; 35%) phases or in the 24 hours postanesthesia (n = 93 animals; 45%). Lesions indicative of significant natural disease were present in 130 of 221 animals (59%), mainly involving the heart, upper respiratory tract, or lungs. Surgical or anesthesia-associated complications were identified in 10 of 221 cases (5%). No lesions were evident in 80 of 221 animals (36%), the majority of which were young, healthy, and undergoing elective surgical procedures. Lesions resulting from cardiopulmonary resuscitation were identified in 75 of 221 animals (34%). Investigation of perianesthetic death cases should be done with knowledge of prior clinical findings and antemortem surgical and medical procedures; the autopsy should particularly focus on the cardiovascular and respiratory system, including techniques to identify pneumothorax and venous air embolism. PMID- 27371540 TI - Feline Epitheliotropic Mastocytic Conjunctivitis in 15 Cats. AB - Mast cell infiltration occurs in malignant, inflammatory (eg, allergic, infectious), and idiopathic disease processes in humans and animals. Here, we describe the clinical and histological features of a unique proliferative conjunctivitis occurring in 15 cats. Ocular specimens were examined histologically, and polymerase chain reaction (PCR) for feline herpesvirus 1 (FHV 1) was performed on ocular tissues obtained from 10 cats. Cats had a median age of 8 years (range: 7 months-17.5 years). The known median duration of ocular lesions prior to biopsy was 4 months (range: 1 week-3 years). Ocular disease was unilateral in 12 cats, and 9 cats had coexisting corneal disease. Clinically and histologically, proliferative or nodular conjunctival lesions were noted in 13 cats. The nictitating membrane was affected in 10 cats. Histologically, lesions were characterized by mixed inflammatory infiltrates with an abundance of Giemsa positive and toluidine blue-positive intraepithelial and subepithelial mast cells, marked edema, and papillary epithelial hyperplasia. Feline herpesvirus 1 was demonstrated by PCR in 1 of 10 cats tested. Follow-up information was available for 14 cats: 8 had no recurrence during a median follow-up period of 17.5 months (range: 4.5-30 months), 2 underwent orbital exenteration, 3 had recurrence that was medically managed, and 1 cat had diffuse conjunctivitis at the time of biopsy and recurrence was deemed irrelevant. Various ocular medications were administered before and after surgical biopsy. This condition was designated as feline epitheliotropic mastocytic conjunctivitis, with intraepithelial mast cells being an essential feature and papillary epithelial proliferation being characteristic but not diagnostic alone. The condition appears to be uncommon and benign. Although the cause is unknown, an allergic component is possible. PMID- 27371541 TI - Senecavirus A. AB - Senecavirus A (SVA) is the only member of the genus Senecavirus within the family Picornaviridae. This virus was discovered as a serendipitous finding in 2002 (and named Seneca Valley virus 001 [SVV-001]) while cultivating viral vectors in cell culture and has been proposed for use as an oncolytic virus to treat different types of human neoplasia. SVA was found in lesions in pigs affected by porcine idiopathic vesicular disease in Canada and the USA in 2008 and 2012, respectively. In 2014 and 2015, SVA infection was associated with outbreaks of vesicular disease in sows as well as neonatal pig mortality in Brazil and the USA. Phylogenetic analysis of the SVA VP1 indicates the existence of 3 clades of the virus. Clade I contains the historical strain SVV-001, clade II contains USA SVA strains identified between 1988 and 1997, and clade III contains global SVA strains from Brazil, Canada, China, and the USA identified between 2001 and 2015. The aim of this review is to draw the attention of veterinarians and researchers to a recently described infectious clinical-pathologic condition caused by a previously known agent (SVA). Apart from the intrinsic interest in a novel virus infecting pigs and causing economic losses, the major current concern is the similarity of the clinical picture to that of other swine diseases, because one of them-foot and mouth disease-is a World Organization for Animal Health-listed disease. Because the potential association of SVA with disease is rather new, there are still many questions to be resolved. PMID- 27371542 TI - A Perspective on Veterinary Forensic Pathology and Medicine in the United Kingdom. AB - Internationally, forensic medicine and pathology are increasingly recognized as an important aspect of work done by veterinary clinicians and veterinary pathologists. In this article, a forensic veterinary clinician, a forensic veterinary pathologist in private practice, and a forensic veterinary pathologist at a veterinary school discuss the interactions among veterinary clinicians, veterinary pathologists, and law enforcement agencies and how future interactions can be improved. The focus is on the United Kingdom, but many of the principles, challenges, and suggestions are applicable to other jurisdictions. Clinicians and pathologists require forensic training to enable them to apply their veterinary knowledge to suspected cases of animal abuse and to subsequently present their findings and conclusions to a court of law in a concise, professional, and unbiased manner, and some opportunities for such advanced training in the United Kingdom are indicated. It is important that forensic veterinary clinicians and pathologists interact in an unbiased and collegial manner to answer the questions posed by courts of law. Opportunities for improved training, communication, and interaction among forensic veterinarians, forensic scientists, and law enforcement are discussed. PMID- 27371543 TI - [Anesthesiological approach for patients with spinal cord injuries]. AB - Spinal cord injuries (SCI) are serious medical conditions, which are associated with severe and potentially fatal risks and complications depending on the location and extent of injury. Traffic accidents, falls and recreational activities are the leading causes for traumatic SCI (TSCI) worldwide whereas non traumatic spinal cord injuries (NTSCI) are mostly due to tumors and congenital diseases. As chronification of the injuries progresses other organ systems are affected including anatomical changes, the respiratory and cardiovascular systems and endocrinological pathways. All these effects have to be considered in the anesthesiological management of patients with SCI. Autonomic dysreflexia (AD) is the most dangerous and life-threatening complication in patients with chronic SCI above T6 that results from an overstimulation of sympathetic reflex circuits in the upper thoracic spine and can be fatal. This article summarizes the specific pathophysiology of SCI and how AD can be avoided as well as also providing anesthetists with strategies for perioperative and intensive care management of patients with SCI. PMID- 27371544 TI - Clinical Experience With Pharmacological Venous Thromboembolism Prophylaxis in the Underweight and Critically Ill. AB - BACKGROUND: The optimal regimen for pharmacological prophylaxis of venous thromboembolism (VTE) in underweight, critically ill patients is unknown. OBJECTIVE: To describe prescribing patterns for VTE prophylaxis in underweight (<=50 kg or body mass index <=18.5 kg/m(2)), critically ill patients and identify the prevalence of VTE and bleeding. METHODS: This was a retrospective cohort study that included patients who received standard- or reduced-dose VTE prophylaxis for >=48 hours. RESULTS: A total of 295 individuals were included in the study. The majority of underweight patients in this study (79.7%) received unfractionated heparin, 5000 units 3 times daily. No statistically significant difference in the prevalence of clinically relevant VTEs between the reduced- and standard-dose groups was observed (4.4% vs 5.6%, P = 1.00), but a higher proportion of bleeding events was identified within the standard-dose group (6.7% vs 11.2%, P = 0.4). CONCLUSIONS: Empirical dose reductions of VTE prophylaxis are infrequently used in underweight, critically ill patients. Further studies need to be conducted that assess the safety and efficacy of reduced-dose VTE prophylactic regimens in this population to determine if acceptable efficacy can be achieved, with lower risks of bleeding. PMID- 27371545 TI - Lincomycin-Induced Acute Generalized Exanthematous Pustulosis Confirmed by Delayed Reading of Intradermal Testing. PMID- 27371546 TI - [Robot-assisted gastrectomy for cancer. German version]. AB - BACKGROUND: Laparoscopic gastrectomy for cancer is commonly considered a challenging procedure. The technical drawbacks of laparoscopy have been addressed by robotic technology, which can facilitate demanding reconstructions and fine dissection. These features confer potential advantages in the execution of lymphadenectomy. OBJECTIVES: Here, we illustrate our technique of robotic gastrectomy and discuss advantages and drawbacks by reviewing the current literature. MATERIALS AND METHODS: We describe our technique for robot-assisted distal and total gastrectomy for cancer and assess the current literature dealing with short-term outcomes, immediate oncologic measures, and long-term oncologic outcomes of robot-assisted gastrectomy, in comparison with conventional laparoscopic and open surgery. RESULTS: The robotic procedure seems to be as safe and effective as conventional gastrectomy for gastric cancer, with a longer operative time and decreased blood loss in comparison with laparoscopic gastrectomy. CONCLUSION: The technical advantages offered by robotics could help to standardize minimally invasive D2 lymphadenectomy and enable surgeons to perform this procedure routinely. Despite the scarcity of long-termdata on survival, immediate oncological measures (lymph node yield and margin status) are encouraging. Further studies investigating the long-term oncological outcomes are required. PMID- 27371547 TI - Validation of Quantitative Measures of Rotatory Knee Laxity. AB - BACKGROUND: Prior attempts to quantify the pivot-shift examination have been too invasive or impractical for clinical use. A noninvasive method for quantifying rotatory knee laxity is needed. HYPOTHESIS: Greater quantitative measurements of rotatory knee laxity (both of the involved knee as well as compared with the contralateral healthy knee) are associated with an increasing clinical pivot shift grade. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A total of 103 patients undergoing anatomic single-bundle anterior cruciate ligament (ACL) reconstruction at 4 international centers underwent a standardized pivot-shift test preoperatively on both knees while anesthetized. Clinical grading of the pivot shift was performed according to the International Knee Documentation Committee (IKDC) knee ligament rating system. Two different quantitative technologies were used to measure rotatory knee laxity: an inertial sensor and an image analysis were independently used to measure tibial acceleration and lateral compartment translation, respectively, during the pivot shift test. Patients were dichotomized to "high-grade" (abnormal and severely abnormal) or "low-grade" (normal and nearly normal) rotatory knee laxity groups based on the clinical pivot-shift test result of the involved side. Tibial acceleration and lateral compartment translation of the involved knee and the side-to-side difference between the involved and contralateral knees were separately compared between the high- and low-grade rotatory knee laxity groups utilizing t tests; significance was set at P < .05. RESULTS: Forty-three patients were in the low-grade rotatory knee laxity group, and 60 patients were in the high-grade rotatory knee laxity group. Patients in the high-grade knee laxity group had significantly higher lateral compartment translation as measured with the image analysis (involved knee: 3.8 +/- 2.3 mm; side-to-side difference: 2.5 +/- 2.4 mm) compared with patients in the low-grade group (involved knee: 2.0 +/- 1.4 mm; side-to-side difference: 1.4 +/- 1.5 mm) (both P < .01). As measured with the inertial sensor, tibial acceleration for patients in the high-grade group was significantly higher (involved knee: 7.2 +/- 5.3 m/s(2); side-to-side difference: 4.2 +/- 5.4 m/s(2)) compared with patients in the low-grade group (involved knee: 4.2 +/- 1.6 m/s(2); side-to-side difference: 1.2 +/- 1.2 m/s(2)) (both P < .01). CONCLUSION: The inertial sensor and image analysis techniques were able to detect differences between low- and high-grade pivot-shift test results. A quantitative assessment of the pivot-shift test could augment the diagnosis of an ACL injury and improve the ability to detect changes in rotatory knee laxity over time. PMID- 27371548 TI - Frequency and Outcomes of a Symptom-Free Waiting Period After Sport-Related Concussion. AB - BACKGROUND: Guidelines and practices for the management of sport-related concussion (SRC) have evolved swiftly over the past 2 decades. Despite common recommendations for a symptom-free waiting period (SFWP) before returning to sport, past reports have suggested poor utilization rates for this intervention. PURPOSE: To obtain current estimates of the utilization and characterization of SFWPs with high school and collegiate athletes. STUDY DESIGN: Descriptive epidemiology study. METHODS: Data were extracted from a larger prospective study that followed athletes with SRC across 13 institutions in southeastern Wisconsin from 2012 to 2014. Participants included 143 contact and collision sport athletes who were followed serially through their recoveries after SRCs. RESULTS: In the current study sample, 99.3% of athletes used an SFWP. The mean self-reported symptom duration was 6.35 days (median, 5 days), with 72.7% reporting symptom recovery within 1 week of injury, 93.7% within 2 weeks, and 99.3% within 30 days. Rate of same-season repeat concussion was low (3.8%) and was similar to or lower than the overall rate of concussion (4.3%). Five same-season repeat concussions occurred at a range of 8 to 42 days after initial injuries. CONCLUSION: In comparison with prior published data collected from 1999 to 2004, utilization and duration of SFWPs were higher in the current study samples (99.3% vs 60.3% of athletes reported an SFWP; mean duration, 6.1 vs 3.2 days), and athletes were withheld from sports for more days than previously reported (12.3 vs 7.4 days). Rate of same-season repeat concussion was equivalent to that of prior published data. The findings support improved adherence to clinical management guidelines through increased utilization of SFWPs after SRC. PMID- 27371549 TI - Does addressing gender inequalities and empowering women and girls improve health and development programme outcomes? AB - This article presents evidence supporting the hypothesis that promoting gender equality and women's and girls' empowerment (GEWE) leads to better health and development outcomes. We reviewed the literature across six sectors-family planning (FP); maternal, newborn and child health (MNCH); nutrition; agriculture; water, sanitation and hygiene; and financial services for the poor-and found 76 studies from low and middle-income countries that met our inclusion criteria. Across these studies, we identified common GEWE variables that emerged repeatedly as significant predictors of sector outcomes. We grouped these variables into 10 thematic categories, which we termed 'gender-related levers'. These levers were then classified by the strength of evidence into Wedges, Foundations and Facilitators. Wedges are gender-related levers that had strong associations with improved outcomes across multiple sectors. They include: 'control over income/assets/resources', 'decision-making power' and 'education'. Elements of these levers overlap, but combined, they encapsulate agency. Increasing female agency promotes equality and broadly improves health and development for women, their families and their communities. The second classification, Foundations, displayed strong, positive associations across FP, MNCH and nutrition. Foundations have a more proximal relationship with sector outcomes and include: 'equitable interpersonal relationships', 'mobility' and 'personal safety'. Finally, the third group of levers, Facilitators, was associated with improved outcomes in two to three sectors and include: 'access to information', 'community groups', 'paid labour' and 'rights'. These levers make it easier for women and girls to achieve their goals and are more traditional elements of development programmes. Overall, gender-related levers were associated with improvements in a variety of health and development outcomes. Furthermore, these associations were cross-sectoral, suggesting that to fully realize the benefits of promoting GEWE, the development community must collaborate in co-ordinated and integrated ways across multiple sectors. More research is needed to identify the mechanisms by which gendered interventions work and under what circumstances. PMID- 27371550 TI - A scoping review of cost benefit analysis in reproductive, maternal, newborn and child health: What we know and what are the gaps? AB - Growing evidence suggests that early life investments in health are associated with improved human capital and economic outcomes. Various recent global studies have simulated the expected economic returns from alternative packages of interventions in reproductive, maternal, newborn and child health (RMNCH). However, very little is known about the comparability of estimates of the economic returns of RMNCH interventions across studies in low and middle income countries. Our study aims to fill this gap. We performed a comprehensive scoping review of the recent literature (2000-2013) on the economic returns (i.e. benefit cost ratios) of RMNCH-related interventions, conducted in low and middle income countries. A total of 36 studies were identified. They were read in full and information was abstracted on both the estimates of benefit-cost ratios, the methodological approach and assumptions used. The estimated economic returns fluctuated considerably across settings as the associated costs of disease patterns, social behaviours and health systems varied. Yet, greater sources of variation stemmed from differences in methodology. The observed methodological inconsistencies limit the accuracy and comparability of the estimated returns across various contexts. The reviewed studies suggest that the benefit-cost ratios are favourable in the majority of cases, providing further support to a growing body of economic literature that suggests investments early in life, such as those interventions related to RMNCH, are good investments. Beyond advocacy purposes, for the reviewed literature to be used by policymakers to inform their decisions on investments, a consistent methodological approach should be adopted. PMID- 27371551 TI - Simple Tools to Facilitate Project Management of a Nursing Research Project. AB - Highly organized project management facilitates rigorous study implementation. Research involves gathering large amounts of information that can be overwhelming when organizational strategies are not used. We describe a variety of project management and organizational tools used in different studies that may be particularly useful for novice researchers. The studies were a multisite study of caregivers of stroke survivors, an Internet-based diary study of women with migraines, and a pilot study testing a sleep intervention in mothers of low-birth weight infants. Project management tools were used to facilitate enrollment, data collection, and access to results. The tools included protocol and eligibility checklists, event calendars, screening and enrollment logs, instrument scoring tables, and data summary sheets. These tools created efficiency, promoted a positive image, minimized errors, and provided researchers with a sense of control. For the studies described, there were no protocol violations, there were minimal missing data, and the integrity of data collection was maintained. PMID- 27371552 TI - Population attributable risk estimates for factors associated with non-use of postnatal care services among women in Nigeria. AB - OBJECTIVES: To determine population attributable risks (PARs) estimates for factors associated with non-use of postnatal care (PNC) in Nigeria. DESIGN, SETTING AND PARTICIPANTS: The most recent Nigeria Demographic and Health Survey (NDHS, 2013) was examined. The study consisted of 20 467 mothers aged 15-49 years. Non-use of PNC services was examined against a set of demographic, health knowledge and social structure factors, using multilevel regression analysis. PARs estimates were obtained for each factor associated with non-use of PNC in the final multivariate logistic regression model. MAIN OUTCOME: PNC services. RESULTS: Non-use of PNC services was attributed to 68% (95% CI 56% to 76%) of mothers who delivered at home, 61% (95% CI 55% to 75%) of those who delivered with the help of non-health professionals and 37% (95% CI 31% to 45%) of those who lacked knowledge of delivery complications in the study population. Multiple variable analyses revealed that non-use of PNC services among mothers was significantly associated with rural residence, household poverty, no or low levels of mothers' formal education, small perceived size of neonate, poor knowledge of delivery-related complications, and limited or no access to the mass media. CONCLUSIONS: PAR estimates for factors associated with non-use of PNC in Nigeria highlight the need for community-based interventions regarding maternal education and services that focus on mothers who delivered their babies at home. Our study also recommends financial support from the Nigerian government for mothers from low socioeconomic settings, so as to minimise the inequitable access to pregnancy and delivery healthcare services with trained healthcare personnel. PMID- 27371553 TI - Validation of administrative hospital data for identifying incident pancreatic and periampullary cancer cases: a population-based study using linked cancer registry and administrative hospital data in New South Wales, Australia. AB - OBJECTIVES: Informing cancer service delivery with timely and accurate data is essential to cancer control activities and health system monitoring. This study aimed to assess the validity of ascertaining incident cases and resection use for pancreatic and periampullary cancers from linked administrative hospital data, compared with data from a cancer registry (the 'gold standard'). DESIGN, SETTING AND PARTICIPANTS: Analysis of linked statutory population-based cancer registry data and administrative hospital data for adults (aged >=18 years) with a pancreatic or periampullary cancer case diagnosed during 2005-2009 or a hospital admission for these cancers between 2005 and 2013 in New South Wales, Australia. METHODS: The sensitivity and positive predictive value (PPV) of pancreatic and periampullary cancer case ascertainment from hospital admission data were calculated for the 2005-2009 period through comparison with registry data. We examined the effect of the look-back period to distinguish incident cancer cases from prevalent cancer cases from hospital admission data using 2009 and 2013 as index years. RESULTS: Sensitivity of case ascertainment from the hospital data was 87.5% (4322/4939), with higher sensitivity when the cancer was resected (97.9%, 715/730) and for pancreatic cancers (88.6%, 3733/4211). Sensitivity was lower in regional (83.3%) and remote (85.7%) areas, particularly in areas with interstate outflow of patients for treatment, and for cases notified to the registry by death certificate only (9.6%). The PPV for the identification of incident cases was 82.0% (4322/5272). A 2-year look-back period distinguished the majority (98%) of incident cases from prevalent cases in linked hospital data. CONCLUSIONS: Pancreatic and periampullary cancer cases and resection use can be ascertained from linked hospital admission data with sufficient validity for informing aspects of health service delivery and system-level monitoring. Limited tumour clinical information and variation in case ascertainment across population subgroups are limitations of hospital-derived cancer incidence data when compared with population cancer registries. PMID- 27371554 TI - Association of inpatient hospital experience with patient safety indicators: a cross-sectional, Canadian study. AB - OBJECTIVES: There remains concern regarding the use of survey data to assess aspects of healthcare quality. The relationship between patient experience and adverse events as documented by patient safety indicators (PSIs) is a timely research topic. The objectives were to document the association of PSIs and patient experience scores, and to determine risk-adjusted odds of high experience scores versus PSI presence. SETTING AND PARTICIPANTS: From April 2011 to March 2014, 25 098 patients completed a telephone survey following discharge from 93 inpatient hospitals in Alberta, Canada. RESEARCH DESIGN: A modified version of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) instrument was used. Surveys were linked to inpatient records and PSI presence was documented using a validated algorithm. MEASURES: Three questions about overall hospital, physician and nurse ratings were scored on an 11-point Likert scale from 0 (worst) to 10 (best). Experience was classified as high (9 or 10) versus low (0-8). Demographic/clinical differences between respondents with/without a PSI were assessed. Logistic regression examined the relationship between factors including PSI and experience ratings. RESULTS: Overall, physician and nurse care was rated high by 61.9%, 73.7% and 66.2% of respondents. 1085 patients (4.3%) had a documented PSI. Most frequent PSIs were haemorrhagic events (n=502; 2.0% of sample), events relating to obstetrics (n=373; 1.5%) and surgical related events (n=248; 1.0%). Risk-adjusted models showed patients with PSIs had decreased odds of having high overall (OR=0.86; 95% CI 0.75 to 0.97), physician (OR=0.76; 95% CI 0.66 to 0.87) and nurse (OR=0.83; 95% CI 0.73 to 0.94) ratings. CONCLUSIONS: There is clear evidence that inpatient experience ratings are associated with PSIs, one element of quality of care. Future research, examining individual PSIs and patient experience questions, is warranted, as this may inform targeted quality improvement initiatives. PMID- 27371555 TI - Impact of approaches in improving male partner involvement in the prevention of mother-to-child transmission (PMTCT) of HIV on the uptake of PMTCT services in sub-Saharan Africa: a protocol of a systematic review and meta-analysis. AB - INTRODUCTION: Several studies have reported approaches used in improving the delivery of prevention of mother-to-child transmission (PMTCT) of HIV services through the involvement of male partners, but evidence from a systematic review is limited. We aim at determining the impact of male partner involvement on PMTCT in sub-Saharan Africa. METHODS AND ANALYSIS: This will be a systematic review of published literature. Interventional and observational studies on male involvement in PMTCT carried out in sub-Saharan Africa will be included irrespective of the year and language of publication. OVID Medline, Embase, PschINFO, and Cochrane database of controlled trials will be searched. After manual searching of articles, authors shall be contacted for further information. 2 authors (NFT and CJ) will independently screen potential articles for eligibility using defined inclusion and exclusion criteria. Critical Appraisal Skills Programme (CASP) tools, Jadad scale and the STROBE checklist will be used for critical appraisal, and the 2 authors will independently assess the quality of articles. Authors will independently extract data from studies using a pre established data collection form, and any discrepancies will be sorted by a third author (TRK). Outcomes will be analysed using STATA V.12.0. The random effect model will be used to produce forest plots. The heterogeneity chi(2) statistics and I(2) will be used to assess for heterogeneity. Publication bias will be assessed using funnel plots. This protocol is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines. ETHICS AND DISSEMINATION: No ethical approval since included studies will be published studies that had already obtained ethical approvals. The findings will guide HIV programmes on the best approaches towards involving male partners in PMTCT with a view to improving PMTCT services in sub-Saharan Africa. PROSPERO REGISTRATION NUMBER: 42016032673. PMID- 27371557 TI - Awards, Scholarships, and Grants Awarded at the SICB Meeting in January 2016. PMID- 27371558 TI - Awards, Scholarships, and Grants Awarded at the SICB Meeting in January 2016. PMID- 27371559 TI - Announcement of New Members. PMID- 27371556 TI - Seroepidemiology of Toxoplasma gondii in pregnant women in Aguascalientes City, Mexico: a cross-sectional study. AB - OBJECTIVES: We determined the seroprevalence and correlates of Toxoplasma gondii infection in pregnant women in Aguascalientes City, Mexico. DESIGN: A cross sectional survey. SETTING: Pregnant women were enrolled in the central Mexican city of Aguascalientes. PARTICIPANTS: We studied 338 pregnant women who attended prenatal care in 3 public health centres. PRIMARY AND SECONDARY OUTCOME MEASURES: Women were examined for IgG/IgM antibodies to T. gondii by using commercially available enzyme immunoassays, and an avidity test. Multiple analyses were used to determine the association of T. gondii seropositivity with the characteristics of the pregnant women. RESULTS: Of the 338 pregnant women studied, 21 (6.2%) had IgG antibodies to T. gondii, and 1 (4.8%) of them was also positive for IgM antibodies to T. gondii. Avidity of IgG antibodies to T. gondii was high in the IgM-positive sample. Logistic regression analysis of sociodemographic, behavioural and housing variables showed that T. gondii seropositivity was associated with white ethnicity (OR=149.4; 95% CI 10.8 to 2054.1; p<0.01), not washing hands before eating (OR=6.41; 95% CI 1.73 to 23.6; p=0.005) and use of latrine (OR=37.6; 95% CI 4.63 to 306.31; p=0.001). CONCLUSIONS: Results demonstrate that pregnant women in Aguascalientes City have a low seroprevalence of T. gondii infection. However, this low prevalence indicates that most pregnant women are at risk for a primary infection. Factors associated with T. gondii exposure found in this study, including food hygiene, may be useful to determine preventive measures against T. gondii infection and its sequelae. PMID- 27371560 TI - Impacts of Climate Variability and Change on (Marine) Animals: Physiological Underpinnings and Evolutionary Consequences. AB - Understanding thermal ranges and limits of organisms becomes important in light of climate change and observed effects on ecosystems as reported by the IPCC (2014). Evolutionary adaptation to temperature is presently unable to keep animals and other organisms in place; if they can these rather follow the moving isotherms. These effects of climate change on aquatic and terrestrial ecosystems have brought into focus the mechanisms by which temperature and its oscillations shape the biogeography and survival of species. For animals, the integrative concept of oxygen and capacity limited thermal tolerance (OCLTT) has successfully characterized the sublethal limits to performance and the consequences of such limits for ecosystems. Recent models illustrate how routine energy demand defines the realized niche. Steady state temperature-dependent performance profiles thus trace the thermal window and indicate a key role for aerobic metabolism, and the resulting budget of available energy (power), in defining performance under routine conditions, from growth to exercise and reproduction. Differences in the performance and productivity of marine species across latitudes relate to changes in mitochondrial density, capacity, and other features of cellular design. Comparative studies indicate how and why such mechanisms underpinning OCLTT may have developed on evolutionary timescales in different climatic zones and contributed to shaping the functional characteristics and species richness of the respective fauna. A cause-and-effect understanding emerges from considering the relationships between fluctuations in body temperature, cellular design, and performance. Such principles may also have been involved in shaping the functional characteristics of survivors in mass extinction events during earth's history; furthermore, they may provide access to understanding the evolution of endothermy in mammals and birds. Accordingly, an understanding is emerging how climate changes and variability throughout earth's history have influenced animal evolution and co-defined their success or failure from a bio-energetic point of view. Deepening such understanding may further reduce uncertainty about projected impacts of anthropogenic climate variability and change on the distribution, productivity and last not least, survival of aquatic and terrestrial species. PMID- 27371561 TI - The Vulnerability of Tropical Ectotherms to Warming Is Modulated by the Microclimatic Heterogeneity. AB - Most tropical ectotherms live near their physiological limits for temperature. Substantial ecological effects of global change are predicted in the tropics despite the low amplitude of temperature change. These predictions assume that tropical ectotherms experience air temperature as measured by weather stations or predicted by global circulation models. The body temperature of ectotherms, however, can deviate from ambient air when the organism samples the mosaic of microclimates at fine scales. The thermal heterogeneity of tropical landscapes has been quantified only rarely in comparison to temperate habitats, limiting our ability to infer the vulnerability to warming of tropical ectotherms. Here, we used thermal imaging to quantify the heterogeneity in surface temperatures across spatial scales, from the micro- up to landscape scale, at the top of an Inselberg in French Guiana. We measured the thermal heterogeneity at the scale of Clusia nemorosa leaves, by categorizing leaves in full sun versus leaves in the shade to quantify the microclimatic variance available to phytophagous insects. Then, we measured the thermal heterogeneity at the scales of the single shrub and the landscape, for several sites differing in their orientation toward the sun to quantify the microclimatic heterogeneity available for larger ectotherms. All measurements were made three times per day over four consecutive days. There was a high level of thermal heterogeneity at all spatial scales. The thermal variance varied between scales, increasing from the within-leaf surface to the landscape scale. It also shifted across the day in different ways depending on the spatial scale. Then, using a set of published data, we compared the critical temperature (CTmax) of neo-tropical ectotherms and temperature distributions. The portion of space above the CTmax varied substantially depending on spatial scale and taxa. Insects were particularly at risk at the surface of leaves exposed to solar radiation but not on shaded leaves. By contrast, ants tolerated elevated surface temperatures and can survive almost anywhere in the habitat. We suggest that the fine scale mosaic of microclimates in the tropics modulates the vulnerability of ectotherms to warming. By moving just a few meters, or even a few centimeters, small tropical ectotherms can radically change their microclimatic temperature and escape overheating. PMID- 27371562 TI - Follicle-stimulating Hormone (FSH) Phosphorylation of Protein Kinase B (AKT) Remains Controversial. PMID- 27371563 TI - Structural and biochemical insight into the mechanism of Rv2837c from Mycobacterium tuberculosis as a c-di-NMP phosphodiesterase. PMID- 27371564 TI - Fractalkine attenuates excito-neurotoxicity via microglial clearance of damaged neurons and antioxidant enzyme heme oxygenase-1 expression. PMID- 27371565 TI - Glypican-1 stimulates Skp2 autoinduction loop and G1/S transition in endothelial cells. PMID- 27371566 TI - Galphaq-mediated activation of GRK2 by mechanical stretch in cardiac myocytes. THE ROLE OF PROTEIN KINASE C. PMID- 27371567 TI - Peroxisome proliferator-activated receptor beta/delta induces myogenesis by modulating myostatin activity. PMID- 27371568 TI - Myostatin induces insulin resistance via Casitas B-lineage lymphoma b (Cblb) mediated degradation of insulin receptor substrate 1 (IRS1) in response to high calorie diet intake. PMID- 27371569 TI - Pericentric heterochromatin generated by HP1 protein interaction-defective histone methyltransferase Suv39h1. PMID- 27371570 TI - Multidrug resistance-associated protein-1 (MRP-1)-dependent glutathione disulfide (GSSG) efflux as a critical survival factor for oxidant-enriched tumorigenic endothelial cells. PMID- 27371571 TI - The Journal of Biological Chemistry: 2016 Onward. PMID- 27371574 TI - Election 2016: Voting on Variants. AB - Genome sequencing studies increasingly identify variants of unknown significance in provocative genes. Kim and colleagues present a system with which to functionally annotate such variants in a high-throughput, biologically relevant series of assays. Cancer Discov; 6(7); 694-6. (c)2016 AACRSee related article by Kim et al., p. 714. PMID- 27371575 TI - CDK4/6 Inhibitors: Promising Opportunities beyond Breast Cancer. AB - Patnaik and colleagues report on the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of abemaciclib for the treatment of advanced solid cancers, demonstrating antitumor activity in advanced breast cancers as well as glioblastoma, melanoma, non-small cell lung cancer, colorectal cancer, and ovarian cancer. The development of abemaciclib and other CDK4/6 inhibitors should now be fully optimized through the use of novel predictive biomarkers of response and rational combinations. Cancer Discov; 6(7); 697-9. (c)2016 AACRSee related article by Patnaik et al., p. 740. PMID- 27371576 TI - An Achilles' Heel for MLL-Rearranged Leukemias: Writers and Readers of H3 Lysine 36 Dimethylation. AB - Histone H3 lysine 36 dimethylation (H3K36me2), a modification associated with transcriptional activation, is required for mixed-lineage leukemia-dependent transcription and leukemic transformation. In this issue of Cancer Discovery, Zhu and colleagues map the network of readers, writers, and erasers of H3K36me2 and uncover the ASH1L histone methyltransferase as a novel target for therapeutic intervention. Cancer Discov; 6(7); 700-2. (c)2016 AACR.See related article by Zhu and colleagues, p. 770. PMID- 27371577 TI - Help Your Editors to Keep Smiling and a Tenth Birthday Celebration. PMID- 27371578 TI - Linkages Within the Reproductive and Maternal Health Continuum of Care in Bangladesh. AB - The continuum of care (CoC) is a fundamental approach to reproductive, maternal, newborn, and child health policy and programs, but linkages along the CoC are inadequately understood. This article assesses linkages in reproductive and maternal health (RMH) services in Bangladesh using the 2011 Bangladesh Demographic and Health Survey (n = 7170). Antenatal care (ANC) was positively associated with skilled birth attendance (SBA) among both pre-pregnancy contraceptive users and nonusers. Among women who used pre-pregnancy contraceptives but did not receive skilled ANC, there was a 26% decreased odds of SBA. Pre-pregnancy contraceptive use increased the odds of postpartum contraceptive use, but neither ANC nor SBA was associated with postpartum contraceptive use. There are clear linkages within maternal health services and within reproductive health services, but linkages across life stages were variable. Removing barriers to accessing health services early and addressing barriers in the transitions within RMH care will facilitate sustained engagement along the CoC. PMID- 27371579 TI - The Accessory Genome of Shiga Toxin-Producing Escherichia coli Defines a Persistent Colonization Type in Cattle. AB - Shiga toxin-producing Escherichia coli (STEC) strains can colonize cattle for several months and may, thus, serve as gene reservoirs for the genesis of highly virulent zoonotic enterohemorrhagic E. coli (EHEC). Attempts to reduce the human risk for acquiring EHEC infections should include strategies to control such STEC strains persisting in cattle. We therefore aimed to identify genetic patterns associated with the STEC colonization type in the bovine host. We included 88 persistent colonizing STEC (STEC(per)) (shedding for >=4 months) and 74 sporadically colonizing STEC (STEC(spo)) (shedding for <=2 months) isolates from cattle and 16 bovine STEC isolates with unknown colonization types. Genoserotypes and multilocus sequence types (MLSTs) were determined, and the isolates were probed with a DNA microarray for virulence-associated genes (VAGs). All STEC(per) isolates belonged to only four genoserotypes (O26:H11, O156:H25, O165:H25, O182:H25), which formed three genetic clusters (ST21/396/1705, ST300/688, ST119). In contrast, STEC(spo) isolates were scattered among 28 genoserotypes and 30 MLSTs, with O157:H7 (ST11) and O6:H49 (ST1079) being the most prevalent. The microarray analysis identified 139 unique gene patterns that clustered with the genoserotypes and MLSTs of the strains. While the STEC(per) isolates possessed heterogeneous phylogenetic backgrounds, the accessory genome clustered these isolates together, separating them from the STEC(spo) isolates. Given the vast genetic heterogeneity of bovine STEC strains, defining the genetic patterns distinguishing STEC(per) from STEC(spo) isolates will facilitate the targeted design of new intervention strategies to counteract these zoonotic pathogens at the farm level. IMPORTANCE: Ruminants, especially cattle, are sources of food borne infections by Shiga toxin-producing Escherichia coli (STEC) in humans. Some STEC strains persist in cattle for longer periods of time, while others are detected only sporadically. Persisting strains can serve as gene reservoirs that supply E. coli with virulence factors, thereby generating new outbreak strains. Attempts to reduce the human risk for acquiring STEC infections should therefore include strategies to control such persisting STEC strains. By analyzing representative genes of their core and accessory genomes, we show that bovine STEC with a persistent colonization type emerged independently from sporadically colonizing isolates and evolved in parallel evolutionary branches. However, persistent colonizing strains share similar sets of accessory genes. Defining the genetic patterns that distinguish persistent from sporadically colonizing STEC isolates will facilitate the targeted design of new intervention strategies to counteract these zoonotic pathogens at the farm level. PMID- 27371580 TI - (p)ppGpp-Dependent Persisters Increase the Fitness of Escherichia coli Bacteria Deficient in Isoaspartyl Protein Repair. AB - The l-isoaspartyl protein carboxyl methyltransferase (PCM) repairs protein damage resulting from spontaneous conversion of aspartyl or asparaginyl residues to isoaspartate and increases long-term stationary-phase survival of Escherichia coli under stress. In the course of studies intended to examine PCM function in metabolically inactive cells, we identified pcm as a gene whose mutation influences the formation of ofloxacin-tolerant persisters. Specifically, a Deltapcm mutant produced persisters for an extended period in stationary phase, and a DeltaglpD mutation drastically increased persisters in a Deltapcm background, reaching 23% of viable cells. The high-persister double mutant showed much higher competitive fitness than the pcm mutant in competition with wild type during long-term stationary phase, suggesting a link between persistence and the mitigation of unrepaired protein damage. We hypothesized that reduced metabolism in the high-persister strain might retard protein damage but observed no gross differences in metabolism relative to wild-type or single-mutant strains. However, methylglyoxal, which accumulates in glpD mutants, also increased fitness, suggesting a possible mechanism. High-level persister formation in the Deltapcm DeltaglpD mutant was dependent on guanosine pentaphosphate [(p)ppGpp] and polyphosphate. In contrast, persister formation in the Deltapcm mutant was (p)ppGpp independent and thus may occur by a distinct pathway. We also observed an increase in conformationally unstable proteins in the high-persister strain and discuss this as a possible trigger for persistence as a response to unrepaired protein damage. IMPORTANCE: Protein damage is an important factor in the survival and function of cells and organisms. One specific form of protein damage, the formation of the abnormal amino acid isoaspartate, can be repaired by a nearly universally conserved enzyme, PCM. PCM-directed repair is associated with stress survival and longevity in bacteria, insects, worms, plants, mice, and humans, but much remains to be learned about the specific effects of protein damage and repair. This paper identifies an unexpected connection between isoaspartyl protein damage and persisters, subpopulations in bacterial cultures showing increased tolerance to antibiotics. In the absence of PCM, the persister population in Escherichia coli bacteria increased, especially if the metabolic gene glpD was also mutated. High levels of persisters in pcm glpD double mutants correlated with increased fitness of the bacteria in a competition assay, and the fitness was dependent on the signal molecule (p)ppGpp; this may represent an alternative pathway for responding to protein damage. PMID- 27371581 TI - Effects of Specimen Collection Methodologies and Storage Conditions on the Short Term Stability of Oral Microbiome Taxonomy. AB - Community profiling of the oral microbiome requires the recovery of quality sequences in order to accurately describe microbial community structure and composition. Our objective was to assess the effects of specimen collection method, storage medium, and storage conditions on the relative abundance of taxa in saliva and plaque identified using 16S rRNA genes. We also assessed short-term changes in taxon composition and relative abundance and compared the salivary and dental plaque communities in children and adults. Over a 2-week period, four successive saliva and dental plaque specimens were collected from four adults with no dental decay (108 samples), and two successive specimens were collected from six children with four or more erupted teeth (48 samples). There were minimal differences in community composition at the phylum and operational taxonomic unit levels between dental plaque collection using a scaler and collection using a CytoSoft brush. Plaque samples stored in OMNIgene medium showed higher within-sample Shannon diversity, were compositionally different, and were more similar to each other than plaque stored in liquid dental transport medium. Saliva samples stored in OMNIgene recovered similar communities for at least a week following storage at room temperature. However, the microbial communities recovered from plaque and saliva stored in OMNIgene were significantly different in composition from their counterparts stored in liquid dental transport medium. Dental plaque communities collected from the same tooth type over four successive visits from the same adult did not significantly differ in structure or composition. IMPORTANCE: Large-scale epidemiologic studies require collection over time and space, often with multiple teams collecting, storing, and processing data. Therefore, it is essential to understand how sensitive study results are to modest changes in collection and storage protocols that may occur with variation in personnel, resources available at a study site, and shipping requirements. The research presented in this paper measures the effects of multiple storage parameters and collection methodologies on the measured ecology of the oral microbiome from healthy adults and children. These results will potentially enable investigators to conduct oral microbiome studies at maximal efficiency by guiding informed administrative decisions pertaining to the necessary field or clinical work. PMID- 27371582 TI - Multilocus Sequence Analysis of Close Relatives Vibrio anguillarum and Vibrio ordalii. AB - The genetic heterogeneity of the close relatives Vibrio anguillarum and Vibrio ordalii, both serious pathogens of fish causing extensive losses in aquaculture, was studied. Eight housekeeping genes, i.e., atpA, ftsZ, gapA, gyrB, mreB, rpoA, topA, and pyrH, were partially sequenced in 116 isolates from diverse fish species and geographical areas. The eight genes appear to be under purifying selection, and the genetic diversity in the total data set was estimated to be 0.767 +/- 0.026. Our multilocus sequence analysis (MLSA) scheme identified several widespread clonal complexes and resolved the isolates, for the most part, according to serotype. Serotype O2b isolates from diseased cod in Norway, Ireland, and Scotland were found to be extremely homogeneous. Horizontal gene transfer appears to be fairly common within and between clonal complexes. Taken together, MLSA and in silico DNA-DNA hybridization (DDH) calculations suggest that some isolates previously characterized as V ordalii, i.e., 12B09, FF93, FS144, and FS238, are in fact V. anguillarum isolates. The precise taxonomic situation for two isolates from Atlantic cod that display several traits consistent with V. ordalii, i.e., NVI 5286 and NVI 5918, and a single environmental strain that was previously considered to represent V. ordalii, i.e., FF167, is less clear. IMPORTANCE: It is still being debated whether V. anguillarum and V ordalii represent separate bacterial species. Our study addresses this issue and elucidates the degree of genetic variability within this group of closely related bacteria, based on a substantial number of isolates. Our results clearly illustrate the existence of different populations among putative V ordalii isolates. On the basis of additional full-length genomic analysis, we conclude that most environmental isolates previously identified as V ordalii lie firmly within the species V. anguillarum While bona fide fish-pathogenic V ordalii isolates display a very close genetic relationship with V. anguillarum, they combine a clearly divergent evolutionary pattern with clear phenotypic differences. The study also highlights the need for further characterization of fish-pathogenic isolates from the northern Atlantic region that share phenotypic characteristics with V. ordalii but are genetically closer to V. anguillarum The retention of taxonomic distinctions between the phenotypically different groups of bacteria is of practical advantage to microbial ecologists and veterinarians. PMID- 27371583 TI - Evidence of Naturalized Stress-Tolerant Strains of Escherichia coli in Municipal Wastewater Treatment Plants. AB - Escherichia coli has been proposed to have two habitats-the intestines of mammals/birds and the nonhost environment. Our goal was to assess whether certain strains of E. coli have evolved toward adaptation and survival in wastewater. Raw sewage samples from different treatment plants were subjected to chlorine stress, and ~59% of the surviving E. coli strains were found to contain a genetic insertion element (IS30) located within the uspC-flhDC intergenic region. The positional location of the IS30 element was not observed across a library of 845 E. coli isolates collected from various animal hosts or within GenBank or whole genome reference databases for human and animal E. coli isolates (n = 1,177). Phylogenetics clustered the IS30 element-containing wastewater E. coli isolates into a distinct clade, and biomarker analysis revealed that these wastewater isolates contained a single nucleotide polymorphism (SNP) biomarker pattern that was specific for wastewater. These isolates belonged to phylogroup A, possessed generalized stress response (RpoS) activity, and carried the locus of heat resistance, features likely relevant to nonhost environmental survival. Isolates were screened for 28 virulence genes but carried only the fimH marker. Our data suggest that wastewater contains a naturalized resident population of E. coli We developed an endpoint PCR targeting the IS30 element within the uspC-flhDC intergenic region, and all raw sewage samples (n = 21) were positive for this marker. Conversely, the prevalence of this marker in E. coli-positive surface and groundwater samples was low (<=5%). This simple PCR assay may represent a convenient microbial source-tracking tool for identification of water samples affected by municipal wastewater. IMPORTANCE: The results of this study demonstrate that some strains of E. coli appear to have evolved to become naturalized populations in the wastewater environment and possess a number of stress-related genetic elements likely important for survival in this nonhost environment. The presence of non-host-adapted strains in wastewater challenges our understanding of using E. coli as a microbial indicator of wastewater treatment performance, suggesting that the E. coli strains present in human and animal feces may be very different from those found in treated wastewater. PMID- 27371584 TI - Grapevine (Vitis vinifera) Crown Galls Host Distinct Microbiota. AB - Crown gall disease of grapevine is caused by virulent Agrobacterium strains and establishes a suitable habitat for agrobacteria and, potentially, other bacteria. The microbial community associated with grapevine plants has not been investigated with respect to this disease, which frequently results in monetary losses. This study compares the endophytic microbiota of organs from grapevine plants with or without crown gall disease and the surrounding vineyard soil over the growing seasons of 1 year. Amplicon-based community profiling revealed that the dominating factor causing differences between the grapevine microbiota is the sample site, not the crown gall disease. The soil showed the highest microbial diversity, which decreased with the distance from the soil over the root and the graft union of the trunk to the cane. Only the graft union microbiota was significantly affected by crown gall disease. The bacterial community of graft unions without a crown gall hosted transient microbiota, with the three most abundant bacterial species changing from season to season. In contrast, graft unions with a crown gall had a higher species richness, which in every season was dominated by the same three bacteria (Pseudomonas sp., Enterobacteriaceae sp., and Agrobacterium vitis). For in vitro-cultivated grapevine plantlets, A. vitis infection alone was sufficient to cause crown gall disease. Our data show that microbiota in crown galls is more stable over time than microbiota in healthy graft unions and that the microbial community is not essential for crown gall disease outbreak. IMPORTANCE: The characterization of bacterial populations in animal and human diseases using high-throughput deep-sequencing technologies, such as 16S amplicon sequencing, will ideally result in the identification of disease-specific microbiota. We analyzed the microbiota of the crown gall disease of grapevine, which is caused by infection with the bacterial pathogen Agrobacterium vitis. All other Agrobacterium species were found to be avirulent, even though they lived together with A. vitis in the same crown gall tumor. As has been reported for human cancer, the crown gall tumor also hosted opportunistic bacteria that are adapted to the tumor microenvironment. Characterization of the microbiota in various diseases using amplicon sequencing may help in early diagnosis, to serve as a preventative measure of disease in the future. PMID- 27371585 TI - A Rapid Method for Quantifying Viable Mycobacterium avium subsp. paratuberculosis in Cellular Infection Assays. AB - Determining the viability of bacteria is a key outcome of in vitro cellular infection assays. Currently, this is done by culture, which is problematic for fastidious slow-growing bacteria such as Mycobacterium avium subsp. paratuberculosis, where it can take up to 4 months to confirm growth. This study aimed to identify an assay that can rapidly quantify the number of viable M. avium subsp. paratuberculosis cells in a cellular sample. Three commercially available bacterial viability assays along with a modified liquid culture method coupled with high-throughput quantitative PCR growth detection were assessed. Criteria for assessment included the ability of each assay to differentiate live and dead M. avium subsp. paratuberculosis organisms and their accuracy at low bacterial concentrations. Using the culture-based method, M. avium subsp. paratuberculosis growth was reliably detected and quantified within 2 weeks. There was a strong linear association between the 2-week growth rate and the initial inoculum concentration. The number of viable M. avium subsp. paratuberculosis cells in an unknown sample was quantified based on the growth rate, by using growth standards. In contrast, none of the commercially available viability assays were suitable for use with samples from in vitro cellular infection assays. IMPORTANCE: Rapid quantification of the viability of Mycobacterium avium subsp. paratuberculosis in samples from in vitro cellular infection assays is important, as it allows these assays to be carried out on a large scale. In vitro cellular infection assays can function as a preliminary screening tool, for vaccine development or antimicrobial screening, and also to extend findings derived from experimental animal trials. Currently, by using culture, it takes up to 4 months to obtain quantifiable results regarding M. avium subsp. paratuberculosis viability after an in vitro infection assay; however, with the quantitative PCR and liquid culture method developed, reliable results can be obtained at 2 weeks. This method will be important for vaccine and antimicrobial screening work, as it will allow a greater number of candidates to be screened in the same amount of time, which will increase the likelihood that a favorable candidate will be found to be subjected to further testing. PMID- 27371586 TI - A Diverse Soil Microbiome Degrades More Crude Oil than Specialized Bacterial Assemblages Obtained in Culture. AB - Soil microbiome modification may alter system function, which may enhance processes like bioremediation. In this study, we filled microcosms with gamma irradiated soil that was reinoculated with the initial soil or cultivated bacterial subsets obtained on regular media (REG-M) or media containing crude oil (CO-M). We allowed 8 weeks for microbiome stabilization, added crude oil and monoammonium phosphate, incubated the microcosms for another 6 weeks, and then measured the biodegradation of crude oil components, bacterial taxonomy, and functional gene composition. We hypothesized that the biodegradation of targeted crude oil components would be enhanced by limiting the microbial taxa competing for resources and by specifically selecting bacteria involved in crude oil biodegradation (i.e., CO-M). Postincubation, large differences in taxonomy and functional gene composition between the three microbiome types remained, indicating that purposeful soil microbiome structuring is feasible. Although phylum-level bacterial taxonomy was constrained, operational taxonomic unit composition varied between microbiome types. Contrary to our hypothesis, the biodegradation of C10 to C50 hydrocarbons was highest when the original microbiome was reinoculated, despite a higher relative abundance of alkane hydroxylase genes in the CO-M microbiomes and of carbon-processing genes in the REG-M microbiomes. Despite increases in the relative abundances of genes potentially linked to hydrocarbon processing in cultivated subsets of the microbiome, reinoculation of the initial microbiome led to maximum biodegradation. IMPORTANCE: In this study, we show that it is possible to sustainably modify microbial assemblages in soil. This has implications for biotechnology, as modification of gut microbial assemblages has led to improved treatments for diseases like Clostridium difficile infection. Although the soil environment determined which major phylogenetic groups of bacteria would dominate the assemblage, we saw differences at lower levels of taxonomy and in functional gene composition (e.g., genes related to hydrocarbon degradation). Further studies are needed to determine the success of such an approach in nonsterile environments. Although the biodegradation of certain crude oil fractions was still the highest when we inoculated with the diverse initial microbiome, the possibility of discovering and establishing microbiomes that are more efficient in crude oil degradation is not precluded. PMID- 27371587 TI - A Small Number of Phylogenetically Distinct Clonal Complexes Dominate a Coastal Vibrio cholerae Population. AB - Vibrio cholerae is a ubiquitous aquatic microbe in temperate and tropical coastal areas. It is a diverse species, with many isolates that are harmless to humans, while others are highly pathogenic. Most notable among them are strains belonging to the pandemic O1/O139 serogroup lineage, which contains the causative agents of cholera. The environmental selective regimes that led to this diversity are key to understanding how pathogens evolve in environmental reservoirs. A local population of V. cholerae and its close relative Vibrio metoecus from a coastal pond and lagoon system was extensively sampled during two consecutive months across four size fractions (480 isolates). In stark contrast to previous studies, the observed population was highly clonal, with 60% of V. cholerae isolates falling into one of five clonal complexes, which varied in abundance in the short temporal scale sampled. V. cholerae clonal complexes had significantly different distributions across size fractions and the two environments sampled, the pond and the lagoon. Sequencing the genomes of 20 isolates representing these five V. cholerae clonal complexes revealed different evolutionary trajectories, with considerable variations in gene content with potential ecological significance. Showing genotypic differentiation and differential spatial distribution, the dominant clonal complexes are likely ecologically divergent. Temporal variation in the relative abundance of these complexes suggests that transient blooms of specific clones could dominate local diversity. IMPORTANCE: Vibrio cholerae is commonly found in coastal areas worldwide, with only a single group of this bacterium capable of causing severe cholera outbreaks. However, the potential to evolve the ability to cause disease exists in many strains of this species in its aquatic reservoir. Understanding how pathogenic bacteria evolve requires the study of their natural environments. By extensive sampling in a geographically restricted location in the United States, we found that most cells of a V. cholerae population belong to only a small number of strains. Analysis of their genome composition and spatial distribution indicates differential environmental adaptations between these strains. Other strains exist in smaller numbers, and the population was found to be temporally varied. This suggests frequent bloom and collapse cycles on a time scale of weeks. These population dynamics make it possible that more virulent strains could stochastically rise to large numbers, allowing for infection to occur. PMID- 27371589 TI - Corrigendum: Growth and the Environment of Schizosaccharomyces pombe. PMID- 27371588 TI - Antimicrobial Effects of Free Nitrous Acid on Desulfovibrio vulgaris: Implications for Sulfide-Induced Corrosion of Concrete. AB - Hydrogen sulfide produced by sulfate-reducing bacteria (SRB) in sewers causes odor problems and asset deterioration due to the sulfide-induced concrete corrosion. Free nitrous acid (FNA) was recently demonstrated as a promising antimicrobial agent to alleviate hydrogen sulfide production in sewers. However, details of the antimicrobial mechanisms of FNA are largely unknown. Here, we report the multiple-targeted antimicrobial effects of FNA on the SRB Desulfovibrio vulgaris Hildenborough by determining the growth, physiological, and gene expression responses to FNA exposure. The activities of growth, respiration, and ATP generation were inhibited when exposed to FNA. These changes were reflected in the transcript levels detected during exposure. The removal of FNA was evident by nitrite reduction that likely involved nitrite reductase and the poorly characterized hybrid cluster protein, and the genes coding for these proteins were highly expressed. During FNA exposure, lowered ribosome activity and protein production were detected. Additionally, conditions within the cells were more oxidizing, and there was evidence of oxidative stress. Based on an interpretation of the measured responses, we present a model depicting the antimicrobial effects of FNA on D. vulgaris These findings provide new insight for understanding the responses of D. vulgaris to FNA and will provide a foundation for optimal application of this antimicrobial agent for improved control of sewer corrosion and odor management.IMPORTANCE Hydrogen sulfide produced by SRB in sewers causes odor problems and results in serious deterioration of sewer assets that requires very costly and demanding rehabilitation. Currently, there is successful application of the antimicrobial agent free nitrous acid (FNA), the protonated form of nitrite, for the control of sulfide levels in sewers (G. Jiang et al., Water Res 47:4331-4339, 2013, http://dx.doi.org/10.1016/j.watres.2013.05.024). However, the details of the antimicrobial mechanisms of FNA are largely unknown. In this study, we identified the key responses (decreased anaerobic respiration, reducing FNA, combating oxidative stress, and shutting down protein synthesis) of Desulfovibrio vulgaris Hildenborough, a model sewer corrosion bacterium, to FNA exposure by examining the growth, physiological, and gene expression changes. These findings provide new insight and underpinning knowledge for understanding the responses of D. vulgaris to FNA exposure, thereby benefiting the practical application of FNA for improved control of sewer corrosion and odor. PMID- 27371590 TI - Erratum: Preparation of Nuclear Extracts from HeLa Cells. PMID- 27371591 TI - Prediction and Validation of Native and Engineered Cas9 Guide Sequences. AB - Cas9-based technologies rely on native elements of Type II CRISPR-Cas bacterial immune systems, including the trans-activating CRISPR RNA (tracrRNA), CRISPR RNA (crRNA), Cas9 protein, and protospacer-adjacent motif (PAM). The tracrRNA and crRNA form an RNA duplex that guides the Cas9 endonuclease to complementary nucleic acid sequences. Mechanistically, Cas9 initiates interactions by binding to the target PAM sequence and interrogating the target DNA in a 3'-to-5' manner. Complementarity between the guide RNA and the target DNA is key. In natural systems, precise cleavage occurs when the target DNA sequence contains a PAM flanking a sequence homologous to the crRNA spacer sequence. Currently, the majority of commercial Cas9-based genome-editing tools are derived from the Type II CRISPR-Cas system of Streptococcus pyogenes However, a diverse set of Type II CRISPR-Cas systems exist in nature that are potentially valuable for genome engineering applications. Exploitation of these systems requires prediction and validation of both native and engineered dual and single guide RNAs to drive Cas9 functionality. Here, we discuss how to identify the elements of these immune systems to develop next-generation Cas9-based genome-editing tools. We first discuss how to predict tracrRNA sequences and suggest a method for designing single guide RNAs containing only critical structural modules. We then outline how to predict the PAM sequence, which is crucial for determining potential targets for Cas9. Finally, validation of the system elements through transcriptome analysis and interference assays is essential for developing next generation Cas9-based genome-editing tools. PMID- 27371592 TI - Triggering Apoptosis in Hematopoietic Cells with Cytotoxic Drugs. AB - Cytotoxic agents are commonly added to cultured cells in the laboratory to investigate their efficacy, mechanism of action, and therapeutic potential. Most of these agents trigger cell death by apoptosis, which is also the most common form of cell death during development, aging, homeostasis, and eradication of disease. Treatment of cells with cytotoxic agents is therefore useful for investigating basic mechanisms of cell death in the human body. Actinomycin D, a cytotoxic agent isolated from Streptomyces, induces apoptosis in a variety of cell lines including the histiocytic lymphoma cell line U937. Treatment of U937 cells with actinomycin D provides an ideal model of drug-induced apoptosis that can also be used as a positive control for comparison with other treatments. PMID- 27371593 TI - Triggering Death of Adherent Cells with Ultraviolet Radiation. AB - Ultraviolet (UV) radiation is a convenient stimulus for triggering cell death that is available in most laboratories. We use a Stratalinker UV cross-linker because it is a safe, cheap, reliable, consistent, and easily controlled source of UV irradiation. This protocol describes using a Stratalinker to trigger UV induced death of HeLa cells. PMID- 27371594 TI - Measuring Cell Death by Trypan Blue Uptake and Light Microscopy. AB - Trypan blue is a colorimetric dye that stains dead cells with a blue color easily observed using light microscopy at low resolution. The staining procedure is rapid and cells can be analyzed within minutes. The number of live (unstained) and dead (blue) cells can be counted using a hemocytometer on a basic upright microscope. Trypan blue staining is therefore a convenient assay for rapidly determining the overall viability of cells in a culture before commencing scientific experimentation, or for quantitating cell death following treatment with any cytotoxic stimuli. PMID- 27371595 TI - Measuring Cell Death by Propidium Iodide Uptake and Flow Cytometry. AB - Propidium iodide (PI) is a small fluorescent molecule that binds to DNA but cannot passively traverse into cells that possess an intact plasma membrane. PI uptake versus exclusion can be used to discriminate dead cells, in which plasma membranes become permeable regardless of the mechanism of death, from live cells with intact membranes. PI is excited by wavelengths between 400 and 600 nm and emits light between 600 and 700 nm, and is therefore compatible with lasers and photodetectors commonly available in flow cytometers. This protocol for PI staining can be used to quantitate cell death in most modern research facilities and universities. PMID- 27371596 TI - Optimized Affinity Capture of Yeast Protein Complexes. AB - Here, we describe an affinity isolation protocol. It uses cryomilled yeast cell powder for producing cell extracts and antibody-conjugated paramagnetic beads for affinity capture. Guidelines for determining the optimal extraction solvent composition are provided. Captured proteins are eluted in a denaturing solvent (sodium dodecyl sulfate polyacrylamide gel electrophoresis sample buffer) for gel based proteomic analyses. Although the procedures can be modified to use other sources of cell extract and other forms of affinity media, to date we have consistently obtained the best results with the method presented. PMID- 27371597 TI - Native Elution of Yeast Protein Complexes Obtained by Affinity Capture. AB - This protocol describes two options for the native (nondenaturing) elution of protein complexes obtained by affinity capture. The first approach involves the elution of complexes purified through a tag that includes a human rhinovirus 3C protease (PreScission protease) cleavage site sequence between the protein of interest and the tag. Incubation with the protease cleaves immobilized complexes from the affinity medium. The second approach involves the release of protein A tagged protein complexes using a competitive elution reagent called PEGylOx. The degree of purity of the native assemblies eluted is sample dependent and strongly influenced by the affinity capture. It should be noted that the efficiency of native elution is commonly lower than that of elution by a denaturing agent (e.g., SDS) and the release of the complex will be limited by the activity of the protease or the inhibition constant (Ki) of the competitive release agent. However, an advantage of native release is that some nonspecifically bound materials tend to stay adsorbed to the affinity medium, providing an eluted fraction of higher purity. Finally, keep in mind that the presence of the protease or elution peptide could potentially affect downstream applications; thus, their removal should be considered. PMID- 27371598 TI - Density Gradient Ultracentrifugation to Isolate Endogenous Protein Complexes after Affinity Capture. AB - This protocol describes the isolation of native protein complexes by density gradient ultracentrifugation. The outcome of an affinity capture and native elution experiment is generally a mixture of (1) the complex(es) associated with the protein of interest under the specific conditions of capture, (2) fragments of the complex generated by degradation or disassembly during the purification procedure, and (3) the protease or reagent used to natively elute the sample. To separate these components and isolate a homogeneous complex, an additional step of purification is required. Rate-zonal density gradient ultracentrifugation is a reliable and powerful technique for separating particles based on their hydrodynamic volume. The density gradient is generated by mixing low- and high density solutions of a suitable low-molecular-weight inert solute (e.g., sucrose or glycerol). The gradient is formed in a solvent that could be any of the solvents used for the affinity capture and native elution and should help to preserve the structure and activity of the assembly. PMID- 27371599 TI - Immunofluorescence Microscopy of Schizosaccharomyces pombe Using Chemical Fixation. AB - Establishing the subcellular distribution of molecules of interest and the dynamics of their spatial control underpins all areas of cell and developmental biology. Although the ability to monitor the distribution of fluorescent fusion proteins has revolutionized cell and developmental biology, indirect immunofluorescence microscopy of fixed samples remains an essential complement to this approach. Immunofluorescence is often a more appropriate approach for the study of subcellular architecture. It avoids potential artifacts caused by studying fusion proteins, which might show altered function under stressful imaging conditions. Furthermore, the quantitative analysis of multiple cells in an unperturbed population by immunofluorescence invariably provides a more accurate assessment of the spatial and temporal control of a particular process than does the analysis of individual cells that is the hallmark of live-cell imaging. Parallel studies of living and fixed cells often provide complementary data sets, both of which can be considered necessary for a comprehensive understanding of molecular function. This protocol provides a method for the visualization of the Schizosaccharomyces pombe microtubule cytoskeleton by indirect immunofluorescence microscopy following chemical fixation with formaldehyde and glutaraldehyde. It includes discussion of common modifications used to monitor the distribution of other fission yeast antigens and forms a basis from which to develop protocols to localize new molecules of interest. PMID- 27371600 TI - Recording Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Currents (Ih) in Neurons. AB - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are voltage gated ion channels that play a crucial role in many physiological processes such as memory formation and spatial navigation. Alterations in expression and function of HCN channels have also been associated with multiple disorders including epilepsy, neuropathic pain, and anxiety/depression. Interestingly, neuronal HCN currents (Ih) have diverse biophysical properties in different neurons. This is likely to be in part caused by the heterogeneity of the HCN subunits expressed in neurons. This variation in biophysical characteristics is likely to influence how Ih affects neuronal activity. Thus, it is important to record Ih directly from individual neurons. This protocol describes voltage-clamp methods that can be used to record neuronal Ih under whole-cell voltage-clamp conditions, in cell-attached mode, or with outside-out patches. The information obtained using this approach can be used in combination with other techniques such as computational modeling to determine the significance of Ih for neuronal function. PMID- 27371601 TI - Protein Complex Purification by Affinity Capture. AB - Affinity capture has become a powerful technique for consistently purifying endogenous protein complexes, facilitating biochemical and biophysical assays on otherwise inaccessible biological assemblies, and enabling broader interactomic exploration. For this procedure, cells are broken and their contents separated and extracted into a solvent, permitting access to target macromolecular complexes thus released in solution. The complexes are specifically enriched from the extract onto a solid medium coupled with an affinity reagent-usually an antibody-that recognizes the target either directly or through an appended affinity tag, allowing subsequent characterization of the complex. Here, we discuss approaches and considerations for purifying endogenous yeast protein complexes by affinity capture. PMID- 27371602 TI - Historical Evolution of Laboratory Strains of Saccharomyces cerevisiae. AB - Budding yeast strains used in the laboratory have had a checkered past. Historically, the choice of strain for any particular experiment depended on the suitability of the strain for the topic of study (e.g., cell cycle vs. meiosis). Many laboratory strains had poor fermentation properties and were not representative of the robust strains used for domestic purposes. Most strains were related to each other, but investigators usually had only vague notions about the extent of their relationships. Isogenicity was difficult to confirm before the advent of molecular genetic techniques. However, their ease of growth and manipulation in laboratory conditions made them "the model" model organism, and they still provided a great deal of fundamental knowledge. Indeed, more than one Nobel Prize has been won using them. Most of these strains continue to be powerful tools, and isogenic derivatives of many of them-including entire collections of deletions, overexpression constructs, and tagged gene products-are now available. Furthermore, many of these strains are now sequenced, providing intimate knowledge of their relationships. Recent collections, new isolates, and the creation of genetically tractable derivatives have expanded the available strains for experiments. But even still, these laboratory strains represent a small fraction of the diversity of yeast. The continued development of new laboratory strains will broaden the potential questions that can be posed. We are now poised to take advantage of this diversity, rather than viewing it as a detriment to controlled experiments. PMID- 27371603 TI - Fixed-Cell Imaging of Schizosaccharomyces pombe. AB - The acknowledged genetic malleability of fission yeast has been matched by impressive cytology to drive major advances in our understanding of basic molecular cell biological processes. In many of the more recent studies, traditional approaches of fixation followed by processing to accommodate classical staining procedures have been superseded by live-cell imaging approaches that monitor the distribution of fusion proteins between a molecule of interest and a fluorescent protein. Although such live-cell imaging is uniquely informative for many questions, fixed-cell imaging remains the better option for others and is an important-sometimes critical-complement to the analysis of fluorescent fusion proteins by live-cell imaging. Here, we discuss the merits of fixed- and live-cell imaging as well as specific issues for fluorescence microscopy imaging of fission yeast. PMID- 27371604 TI - Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Currents in Neurons. AB - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are voltage gated ion channels that activate at potentials more negative than -50 mV and are predominantly permeable to Na(+) and K(+) ions. Four HCN subunits (HCN1-4) have been cloned. These subunits have distinct expression patterns and biophysical properties. In addition, cyclic nucleotides as well as multiple intracellular substances including various kinases and phosphatases modulate the expression and function of the subunits. Hence, the characteristics of the current, Ih, are likely to vary among neuronal subtypes. In many neuronal subtypes, Ih is present postsynaptically, where it plays a critical role in setting the resting membrane potential and the membrane resistance. By influencing these intrinsic properties, Ih will affect synaptic potential shapes and summation and thereby affect neuronal excitability. Additionally, Ih can have an effect on resonance properties and intrinsic neuronal oscillations. In some neurons, Ih may also be present presynaptically in axons and synaptic terminals, where it modulates neuronal transmitter release. Hence the effects of Ih on neuronal excitability are complex. It is, however, necessary to fully understand these as Ih has a significant impact on physiological conditions such as learning as well as pathophysiological states such as epilepsy. PMID- 27371605 TI - Guide RNAs: A Glimpse at the Sequences that Drive CRISPR-Cas Systems. AB - CRISPR-Cas systems provide adaptive immunity in bacteria and archaea. Although there are two main classes of CRISPR-Cas systems defined by gene content, interfering RNA biogenesis, and effector proteins, Type II systems have recently been exploited on a broad scale to develop next-generation genetic engineering and genome-editing tools. Conveniently, Type II systems are streamlined and rely on a single protein, Cas9, and a guide RNA molecule, comprised of a CRISPR RNA (crRNA) and trans-acting CRISPR RNA (tracrRNA), to achieve effective and programmable nucleic acid targeting and cleavage. Currently, most commercially available Cas9-based genome-editing tools use the CRISPR-Cas system from Streptococcus pyogenes (SpyCas9), although many orthogonal Type II systems are available for diverse and multiplexable genome engineering applications. Here, we discuss the biological significance of Type II CRISPR-Cas elements, including the tracrRNA, crRNA, Cas9, and protospacer-adjacent motif (PAM), and look at the native function of these elements to understand how they can be engineered, enhanced, and optimized for genome editing applications. Additionally, we discuss the basis for orthogonal Cas9 and guide RNA systems that would allow researchers to concurrently use multiple Cas9-based systems for different purposes. Understanding the native function of endogenous Type II CRISPR-Cas systems can lead to new Cas9 tool development to expand the genetic manipulation toolbox. PMID- 27371606 TI - Growing potential of small aortic valve with aortic coarctation or interrupted aortic arch after bilateral pulmonary artery banding. AB - OBJECTIVES: Bilateral pulmonary artery banding (bPAB) is utilized for some patients with a ventricular septal defect (VSD) and aortic coarctation (CoA) or interrupted aortic arch (IAA). We evaluated aortic valve (AoV) diameter and patient outcomes following bPAB. METHODS: Between August 2010 and September 2015, 10 consecutive patients with VSD and patent ductus arteriosus-dependent CoA or IAA underwent bPAB because of an AoV diameter of approximately <50% of the normal value (n = 6), severe subaortic stenosis and poor patient condition (n = 1, respectively), or low birthweight (n = 2). RESULTS: Second-stage operations were conventional total repair in five and Damus-Kaye-Stansel anastomosis, aortic arch reconstruction and right ventricle-pulmonary artery shunt (modified Norwood) type repair in five. After modified Norwood-type repair, four patients were Yasui-type repair candidates and one was a Fontan candidate. For all patients, the mean AoV diameter increased from 3.7 +/- 0.7 mm before bPAB to 4.6 +/- 0.8 mm before the second-stage operation. In five patients with CoA or IAA type A, the AoV diameter significantly increased from 3.5 +/- 0.3 mm to 4.5 +/- 0.5 mm during the term between bPAB and the second-stage operation, with an AoV Z-score increase from 5.82 +/- 0.92 to -4.28 +/- 0.86. IAA type B showed a slight increase in the AoV diameter. CONCLUSIONS: Initial palliation with bPAB enables AoV diameter growth in some patients, improving the likelihood of conventional total repair adaptation rate, particularly for CoA or IAA type A. PMID- 27371607 TI - Mediastinal paraganglioma fed by the left circumflex artery. AB - A 60-year-old male patient who previously underwent carotid and jugular paraganglioma resections was referred because of a mediastinal recurrence at the root of the great vessels. Coronary angiography confirmed the circumflex artery of the left coronary artery as the feeding artery of the tumour. The patient underwent surgery due to the tumour's location and malignant potential. Upon mass resection, histopathological examination characterized the tumour as a secondary paraganglioma. Neuroendocrine tumours arising from chromaffin tissues at the extra-adrenal paraganglions of the autonomic nervous system are termed paragangliomas. Clinically, they are divided into functional and non-functional types, depending on their catecholamine secretion. The mediastinal location is exceptional and its treatment is challenging. PMID- 27371608 TI - A clinical score to predict acute kidney injury after cardiac surgery in a Southeast-Asian population. AB - OBJECTIVES: Acute kidney injury (AKI) post-cardiac surgery is associated with significant in-hospital and long-term morbidity. This study aimed to develop a risk score for postoperative AKI in a Southeast-Asian population. METHODS: A total of 2508 patients underwent cardiac surgery at the two main heart centres in Singapore between July 2008 and November 2011, of which 2385 met the inclusion criteria. The primary outcome was AKI, defined using the Acute Kidney Injury Network (AKIN) criteria. The scoring model was developed on the test cohort of 2385 and validated with another 500 prospectively recruited patients. Logistic regression analysis was used to identify independent predictors of AKI. RESULTS: The risk factors in this model are age >=65 years, hypertension, estimate glomerular filtration rate (eGFR) <=60 ml/min, use of intra-aortic balloon pump and cardiopulmonary bypass (CPB) time >=120 min, which were similar to previous AKI risk models. Other risk factors in our model include preoperative anaemia, intraoperative red blood cell transfusion and lowest haematocrit during CPB, which have not been described previously. The clinical score ranged from 0 to 14 points with three major risk categories. The AKI frequencies are as follows: 0-4 points (18%), 5-8 points (39%) and 9-14 points (64%). The area under the receiver operating curve (ROC) for the test cohort was 0.70 (95% CI 0.68-0.72), similar to the validation cohort (0.75; 95% CI 0.70-0.80). CONCLUSIONS: In conclusion, the risk model is valid in predicting AKI post-cardiac surgery and can be used for the early diagnosis and treatment of AKI. PMID- 27371609 TI - Risk factors for infections due to carbapenem-resistant Klebsiella pneumoniae after open heart surgery. AB - OBJECTIVES: Patients undergoing major surgery are at increased risk of developing infections due to resistant organisms, including carbapenem-resistant Klebsiella pneumoniae (CR-Kp). In this study, we assessed risk factors for CR-Kp infections after open heart surgery in a teaching hospital in northern Italy. METHODS: A retrospective study was conducted from January to December 2014. The primary outcome measure was postoperative CR-Kp infection, defined as a time-to-event end point. The effect of potentially related variables was assessed by univariable and multivariable analyses. Secondary end-points were in-hospital mortality and 180-day postoperative mortality. RESULTS: Among 553 patients undergoing open heart surgery, 32 developed CR-Kp infections (6%). In the final multivariable model, CR-Kp colonization [hazard ratio (HR) 227.45, 95% confidence intervals (CI) 67.13-1225.20, P < 0.001], cardiopulmonary bypass time in minutes (HR 1.01, 95% CI 1.01-1.02, P < 0.001), chronic obstructive pulmonary disease (HR 3.99, 95% CI 1.61-9.45, P = 0.004), SOFA score (HR 1.29, 95% CI 1.08-1.53, P = 0.007), preoperative mechanical ventilation (HR 8.10, 95% CI 1.31-48.57, P = 0.026), prolonged mechanical ventilation (HR 2.48, 95% CI 1.08-6.15, P = 0.032) and female sex (HR 2.08, 95% CI 1.00-4.36, P = 0.049) were associated with the development of CR-Kp infection. Increased in-hospital mortality and 180-day mortality were observed in patients who developed CR-Kp infections in comparison with those who did not. CONCLUSIONS: In our cohort, CR-Kp colonization was an important predictor of CR-Kp infection after open heart surgery. CR-Kp infection after surgery significantly affected survival. Preventing colonization is conceivably the most effective current strategy to reduce the impact of CR-Kp. PMID- 27371610 TI - Do rapid deployment aortic valves improve outcomes compared with surgical aortic valve replacement? AB - A best evidence topic was written according to a structured protocol. The question addressed was 'In patients requiring an aortic valve replacement, are rapid deployment aortic valve systems better than conventional aortic valve prostheses in terms of mortality, morbidity and/or valve function?' A total of 508 papers were found using the reported search, of which 11 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The rapid deployment valves (RDVs) implanted in these studies include balloon expandable [Intuity (Edwards Lifesciences, CA, USA) and 3F Enable (Medtronic, MN, USA)] and self-expanding [Perceval (Sorin, Saluggia, Italy)] stented bioprostheses. Available data from these studies demonstrate that rapid deployment valves are invariably associated with shorter aortic cross-clamp times (30-56 vs 49-88 min). Despite this, postoperative mortality (0-5.8 vs 0-6%), ICU (1-3 vs 0.9-2.8 days) and hospital length of stay (6-14.1 vs 6-15.9 days) are similar compared with conventional aortic valve replacement (AVR). However, reduced postoperative bleeding (328 vs 564 ml), blood transfusion requirements (1.4 vs 2.4 units), ventilation time (4.9-9.5 vs 7-16.6 h) and renal injury (5.3 vs 14.7%) have been demonstrated with RDVs indicating possible clinical benefit to shorter procedural time. Importantly, patient risk profiles were similar to or higher across studies in patients undergoing RDVs compared with conventional AVR. From a functional perspective, transvalvular gradients were frequently lower with rapid deployment valves compared with conventional AVR, indicating an improved haemodynamic profile. However, in some studies using the Perceval RDV, the transvalvular gradients were higher than with conventional AVR. Also, mean valve sizes were often larger in those receiving RDVs. Rates of paravalvular regurgitation were similar between RDVs and conventional AVR in most studies, although pacemaker implantation occurred more often with RDV in some studies (2-28.5 vs 0-8.5%). Accepting these limitations, and without long-term data, RDVs would appear to be a reasonable alternative to conventional aortic valve prostheses in selected cases. PMID- 27371611 TI - Cancer stem cells in moderately differentiated oral tongue squamous cell carcinoma express components of the renin-angiotensin system. PMID- 27371612 TI - Intermediate microRNA expression profile in Graves' disease falls between that of normal thyroid tissue and papillary thyroid carcinoma. AB - AIMS: Many studies have previously reported a higher prevalence of papillary thyroid carcinomas (PTC) in patients with Graves' disease (GD). MicroRNAs (miRNAs) are small, non-coding RNAs that are upregulated in PTC compared with benign thyroid tissue. The objective of the study was to examine the miRNA expression of selected miRNAs that are known to be upregulated in PTC in patients with GD. METHODS: Paraffin embedded thyroid tissue from 159 patients with GD was screened for expression of the miRNAs 146b, 181b, 21, 221 and 222 by RT-PCR. The expression profiles of four normal thyroids, 50 PTCs without concomitant GD and 11 patients with untreated GD served as the controls. RESULTS: The expression pattern of these miRNAs in patients with GD is intermediate between that of benign thyroid tissue (p<0.001) and PTC (in three out of five miRNAs, p<0.001). This corresponds to a 15-fold change for GD versus PTC, and a 31-fold change for GD versus normal thyroid tissue. The miRNA expression in 11 papillary microcarcinomas found in our study (a prevalence of 0.07) was not different from that in PTC samples from patients without GD for four of five miRNA types. Furthermore, we found a significant difference in the expression of miRNA 221/222 between treated and untreated GD tissue. CONCLUSIONS: In conclusion, we found an intermediate expression of specific miRNAs in thyroid tissue from patients with GD that fell between the expression levels found in normal thyroid glands and PTC, which suggests a possible influence of certain miRNAs on developing PTC in patients with GD. PMID- 27371613 TI - Differing expression profiles of Notch/enterocyte and Wnt/secretory lineage signallings are associated with morphological diversity of appendiceal tumours. AB - BACKGROUND: Tumours of appendix, including classic carcinoid tumour (CCT), goblet cell carcinoid (GCC), low-grade appendiceal mucinous neoplasm, high-grade appendiceal mucinous neoplasm/mucinous carcinoma (MCA) and non-mucinous adenocarcinoma (NMA), show different and sometimes mixed morphological features. It was hypothesised that these tumours originate from common tumour stem cell(s) with potential of various cell lineage differentiation. In normal intestinal epithelium, absorptive lineage (enterocytes) differentiation is driven by Notch Hes1 pathway, while secretory lineage is driven by Wnt-Math1 pathway and further separated by different downstream signallings into three sublineages (Gfi1 Klf4/Elf3 for goblet cells, Gfi1-Sox9 for Paneth cells and Ngn3-Pdx1/Beta2/Pax4 for enteroendocrine cells). METHODS: The expressions of various signalling proteins in different appendiceal tumours were detected by immunohistochemistry on tumour tissue microarray. RESULTS: CCT showed reduced Hes1/Elf3 and Sox9/Klf4 coupled with elevated Math1, in keeping with endocrine phenotype. As compared with CCT, GCC showed higher Klf4 and similar Ngn3/Pax4, indicative of a shift of differentiation towards goblet cells as well as endocrine cells. GCC displayed a Notch signalling similar to adenocarcinoma. Mucinous tumours showed lower Elf3 than normal appendiceal epithelium and higher Math1/Gfi1/Klf4, suggestive of a differentiation towards less enterocytes but more goblet cells. NMA showed Notch signalling similar to other glandular tumours, but lower Klf4. However, some seemingly paradoxical changes were also observed, probably suggesting gene mutations and/or our incomplete understanding of the intestinal cell differentiation. CONCLUSIONS: Wnt/secretory lineage protein and Notch/absorptive lineage protein expression profiles are generally associated with the tumour cell differentiation and morphological diversity of common appendiceal tumours. PMID- 27371614 TI - Rapamycin results in Bim-mediated loss of thymic regulatory T cells during development in organ culture. AB - Thymus-derived regulatory T cells (Tregs) are essential for the maintenance of immunological tolerance. Diverse signalling pathways contribute to thymic Treg cells (tTregs) development; however, the role of mammalian target of rapamycin (mTOR) remains unclear. Rapamycin is a well-characterized inhibitor of mTOR complex 1 signalling and a potent inducer of Treg cells in the periphery. However, the effect of rapamycin on the development of tTregs is poorly defined. Here we have used thymic organ culture to investigate the effect of rapamycin on tTreg development. We show that, contrary to its effect in the periphery, rapamycin inhibits the development of tTregs in wild-type thymi. The inhibition of tTregs by rapamycin could be rescued by a deficiency of Bim. However, rapamycin did not inhibit the development of antigen-specific TCR transgenic tTregs in response to exogenous peptide antigen, indicating that the development of thymic Foxp3+CD4+ cells was not intrinsically inhibited by rapamycin. Collectively our data demonstrate that rapamycin results in a reduction of tTregs because of Bim-mediated apoptosis of immature tTregs via a cell extrinsic mechanism. These findings are important not only for understanding the mechanism of tTreg induction but also for an appreciation of the impact of the clinical application of rapamycin. PMID- 27371615 TI - Highlights from the Current Issue: July 2016. PMID- 27371616 TI - The Potential of Life with CHEER. PMID- 27371617 TI - Regent: A New Otolaryngology Clinical Data Registry. PMID- 27371618 TI - Bridging the Otolaryngology Peer Review Knowledge Gap: A Call for a Residency Development Program. AB - Current otolaryngology literature and future scientific direction rely heavily on a rigorous peer review process. Just as manuscripts warrant thoughtful review with constructive feedback to the authors, the same can be said for critiques written by novice peer reviewers. Formal scientific peer review training programs are lacking. Recognizing this knowledge gap, Otolaryngology-Head and Neck Surgery is excited to offer its new Resident Reviewer Development Program. All otolaryngology residents who are postgraduate year 2 and above and in excellent academic standing are eligible to participate in this mentored program, during which they will conduct 6 manuscript reviews under the direction of a seasoned reviewer in his or her subspecialty area of interest. By completing reviews alongside a mentor, participants gain the required skills to master the peer review process-a first step that often leads to journal editorial board and associate editor invitations. PMID- 27371619 TI - Ethics of Placebo Control in Trials for Idiopathic Sudden Sensorineural Hearing Loss. AB - Idiopathic sudden sensorineural hearing loss (ISSHL) involves sudden loss of hearing from cochlear or retrocochlear origin of unknown cause. Systemic corticosteroids may be considered in the management of ISSNHL. However, an updated Cochrane systematic review concludes that "the value of steroids in the treatment of idiopathic sudden sensorineural hearing loss remains unclear since the evidence obtained from randomized controlled trials is contradictory in outcome." Therefore, a new clinical trial that addresses this question is mandatory. A first step in its design is to determine if placebo control would be ethically acceptable. We conclude that there is equipoise (uncertainty) about the use of corticosteroids for ISSHL. A new trial is justified-but with the inclusion of interim analyses to detect early imbalances on efficacy or safety and with the ability to stop the trial if needed. PMID- 27371620 TI - Ethics of Placebo Control in Trials for Idiopathic Sudden Sensorineural Hearing Loss: Counterpoint. PMID- 27371621 TI - Meniere's Disease: A CHEER Database Study of Local and Regional Patient Encounter and Procedure Patterns. AB - OBJECTIVE: (1) Integrate practice-based patient encounters using the Dartmouth Atlas Medicare database to understand practice treatments for Meniere's disease (MD). (2) Describe differences in the practice patterns between academic and community providers for MD. STUDY DESIGN: Practice-based research database review. SETTING: CHEER (Creating Healthcare Excellence through Education and Research) network academic and community providers. SUBJECTS AND METHODS: MD patient data were identified with ICD-9 and CPT codes. Demographics, unique visits, and procedures per patient were tabulated. The Dartmouth Atlas of Health Care was used to reference regional health care utilization. Statistical analysis included 1-way analyses of variance, bivariate linear regression, and Student's t tests, with significance set at P < .05. RESULTS: A total of 2071 unique patients with MD were identified from 8 academic and 10 community otolaryngology-head and neck surgery provider centers nationally. Average age was 56.5 years; 63.9% were female; and 91.4% self-reported white ethnicity. There was an average of 3.2 visits per patient. Western providers had the highest average visits per patient. Midwest providers had the highest average procedures per patient. Community providers had more visits per site and per patient than did academic providers. Academic providers had significantly more operative procedures per site (P = .0002) when compared with community providers. Health care service areas with higher total Medicare reimbursements per enrollee did not report significantly more operative procedures being performed. CONCLUSION: This is the first practice based clinical research database study to describe MD practice patterns. We demonstrate that academic otolaryngology-head and neck surgery providers perform significantly more operative procedures than do community providers for MD, and we validate these data with an independent Medicare spending database. PMID- 27371622 TI - Thyroid Disease and Surgery in CHEER: The Nation's Otolaryngology-Head and Neck Surgery Practice-Based Network. AB - OBJECTIVES: (1) Describe thyroid-related diagnoses and procedures in Creating Healthcare Excellence through Education and Research (CHEER) across academic and community sites. (2) Compare management of malignant thyroid disease across these sites. (3) Provide practice-based data related to flexible laryngoscopy vocal fold assessment before and after thyroid surgery based on the American Academy of Otolaryngology-Head and Neck Surgery Foundation's clinical practice guidelines. STUDY DESIGN: Review of retrospective data collection (RDC) database of the CHEER network using ICD-9 and CPT codes related to thyroid conditions. SETTING: Multisite practice-based network. SUBJECTS AND METHODS: There were 3807 thyroid patients (1392 malignant, 2415 benign) with 10,160 unique visits identified from 1 year of patient data in the RDC. Analysis was performed for identified cohort of patients using demographics, site characteristics, and diagnostic and procedural distribution. RESULTS: Mean number of patients with thyroid disease per site was 238 (range, 23-715). In community practices, 19% of patients with thyroid disease had cancer versus 45% in the academic setting (P < .001). While academic sites manage more cancer patients, community sites are also surgically treating thyroid cancer and performed more procedures per cancer patient (4.2 vs 3.5, P < .001). Vocal fold function was assessed by flexible laryngoscopy in 34.0% of preoperative patients and in 3.7% postoperatively. CONCLUSION: This is the first overview of malignant and benign thyroid disease through CHEER. It shows how the RDC can be used alone and with national guidelines to inform of clinical practice patterns in academic and community sites. This demonstrates the potential for future thyroid-related studies utilizing the otolaryngology-head and neck surgery practice-based research network. PMID- 27371623 TI - Tonsillectomy Bleed Rates across the CHEER Practice Research Network: Pursuing Guideline Adherence and Quality Improvement. AB - OBJECTIVES: (1) Compare postoperative bleeding in the CHEER network (Creating Healthcare Excellence through Education and Research) among age groups, diagnoses, and practice types. (2) Report the incidence of bleeding by individual CHEER practice site based on practice guidelines. STUDY DESIGN: Retrospective data collection database review of the CHEER network based on ICD-9 and CPT codes related to tonsillectomy patients. SETTING: Multisite practice-based network. SUBJECTS AND METHODS: A total of 8347 subjects underwent tonsillectomy as determined by procedure code within the retrospective data collection database, and 107 had postoperative hemorrhage. These subjects had demographic information and related diagnoses based on the CPT and ICD-9 codes collected. Postoperative ICD-9 and CPT codes were used to identify patients who also had postoperative bleed. Variables included age (<12 vs >=12 years), diagnoses (infectious vs noninfectious), and practice type (community vs academic). Statistical analysis included multivariate logistic regression variables predictive of postoperative bleeding, with P < .05 considered significant. RESULTS: Thirteen sites contributed data to the study (7 academic, 6 community). There was postoperative bleeding for an overall bleed rate of 1.3%. Patients >=12 years old had a significantly increased bleed rate when compared with the younger group (odds ratio, 5.98; 95% confidence interval: 3.79-9.44; P < .0001). There was no significant difference in bleed rates when practices or diagnoses were compared. CONCLUSION: A site descriptor database built to expedite clinical research can be used for practice assessment and quality improvement. These data were also useful to identify patient risk factors for posttonsillectomy bleed. PMID- 27371624 TI - Multi-institutional Study of Voice Disorders and Voice Therapy Referral: Report from the CHEER Network. AB - OBJECTIVES: To assess perspectives of patients with voice problems and identify factors associated with the likelihood of referral to voice therapy via the CHEER (Creating Healthcare Excellence through Education and Research) practice-based research network infrastructure. STUDY DESIGN: Prospectively enrolled cross sectional study of CHEER patients seen for a voice problem (dysphonia). SETTING: The CHEER network of community and academic sites. METHODS: Patient-reported demographic information, nature and severity of voice problems, clinical diagnoses, and proposed treatment plans were collected. The relationship between patient factors and voice therapy referral was investigated. RESULTS: Patients (N = 249) were identified over 12 months from 10 sites comprising 30 otolaryngology physicians. The majority were women (68%) and white (82%). Most patients reported a recurrent voice problem (72%) and symptom duration >4 weeks (89%). The most commonly reported voice-related diagnoses were vocal strain, reflux, and benign vocal fold lesions. Sixty-seven percent of enrolled patients reported receiving a recommendation for voice therapy. After adjusting for sociodemographic and other factors, diagnoses including vocal strain/excessive tension and vocal fold paralysis and academic practice type were associated with increased likelihood of reporting a referral for voice therapy. CONCLUSIONS: The CHEER network successfully enrolled a representative sample of patients with dysphonia. Common diagnoses were vocal strain, reflux, and benign vocal fold lesions; commonly reported treatment recommendations included speech/voice therapy and antireflux medication. Recommendation for speech/voice therapy was associated with academic practice type. PMID- 27371625 TI - Variation in the Use of Vestibular Diagnostic Testing for Patients Presenting to Otolaryngology Clinics with Dizziness. AB - OBJECTIVE: We used a national otolaryngology practice-based research network database to characterize the utilization of vestibular function testing in patients diagnosed with dizziness and/or a vestibular disorder. STUDY DESIGN: Database review. SETTING: The Creating Healthcare Excellence through Education and Research (CHEER) practice-based research network of academic and community providers SUBJECTS AND METHODS: Dizzy patients in the CHEER retrospective database were identified through ICD-9 codes; vestibular testing procedures were identified with CPT codes. Demographics and procedures per patient were tabulated. Analysis included number and type of vestibular tests ordered, stratified by individual clinic and by practice type (community vs academic). Chi square tests were performed to assess if the percentage of patients receiving testing was statistically significant across clinics. A logistic regression model was used to examine the association between receipt of testing and being tested on initial visit. RESULTS: A total of 12,468 patients diagnosed with dizziness and/or a vestibular disorder were identified from 7 community and 5 academic CHEER network clinics across the country. One-fifth of these patients had at least 1 vestibular function test. The percentage of patients tested varied widely by site, from 3% to 72%; academic clinics were twice as likely to test. Initial visit vestibular testing also varied, from 0% to 96% of dizzy patients, and was 15 times more likely in academic clinics. CONCLUSION: There is significant variation in use and timing of vestibular diagnostic testing across otolaryngology clinics. The CHEER network research database does not contain outcome data. These results illustrate the critical need for research that examines outcomes as related to vestibular testing. PMID- 27371626 TI - Evaluation of Compliance for Treatment of Sudden Hearing Loss: A CHEER Network Study. AB - OBJECTIVE: The objective of this study is to describe the presentation and management of sudden sensorineural hearing loss for patients seen in academic and community-based practices within the context of the American Academy of Otolaryngology-Head and Neck Surgery Foundation's "Clinical Practice Guideline: Sudden Hearing Loss." The intention is to use these findings to guide implementation strategies and quality improvement initiatives and as pilot data for the development of clinical research initiatives. STUDY DESIGN: A cross sectional study of patients with sudden hearing loss. SETTING: Patients were recruited from practices within the Creating Healthcare Excellence through Education and Research (CHEER) network. The CHEER network is an National Institutes of Health-funded network of 30 otolaryngology sites across the country, half of which are community based and half of which are academic practices. SUBJECTS AND METHODS: A total of 173 patients were recruited. Data were gathered via custom questionnaires collected by study site coordinators and entered into a secure online platform. Descriptive analyses and correlation statistics were run with SAS 9.3.1. RESULTS: Of the 13 guideline statements in the American Academy of Otolaryngology-Head and Neck Surgery Foundation's clinical practice guideline on sudden hearing loss, 11 statements were evaluable through this study. Compliance for otolaryngologists was >95% for key action statements (KASs) 1, 3, and 6; 90% to 95% for KASs 5 and 10; and <90% for KASs 7 and 13. Compliance was <45% for nonotolaryngologists for KASs 3 and 5-7. CONCLUSIONS: There is opportunity for nonotolaryngologists to improve for statements 3 and 5-7. Otolaryngologists are compliant with many of the KASs overall, but there is significant room for improvement. PMID- 27371627 TI - Does an Otolaryngology-Specific Database Have Added Value? A Comparative Feasibility Analysis. AB - OBJECTIVES: There are multiple nationally representative databases that support epidemiologic and outcomes research, and it is unknown whether an otolaryngology specific resource would prove indispensable or superfluous. Therefore, our objective was to determine the feasibility of analyses in the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) databases as compared with the otolaryngology-specific Creating Healthcare Excellence through Education and Research (CHEER) database. STUDY DESIGN: Parallel analyses in 2 data sets. SETTING: Ambulatory visits in the United States. SUBJECTS AND METHODS: To test a fixed hypothesis that could be directly compared between data sets, we focused on a condition with expected prevalence high enough to substantiate availability in both. This query also encompassed a broad span of diagnoses to sample the breadth of available information. Specifically, we compared an assessment of suspected risk factors for sensorineural hearing loss in subjects 0 to 21 years of age, according to a predetermined protocol. We also assessed the feasibility of 6 additional diagnostic queries among all age groups. RESULTS: In the NAMCS/NHAMCS data set, the number of measured observations was not sufficient to support reliable numeric conclusions (percentage standard error among risk factors: 38.6-92.1). Analysis of the CHEER database demonstrated that age, sex, meningitis, and cytomegalovirus were statistically significant factors associated with pediatric sensorineural hearing loss (P < .01). Among the 6 additional diagnostic queries assessed, NAMCS/NHAMCS usage was also infeasible; the CHEER database contained 1585 to 212,521 more observations per annum. CONCLUSION: An otolaryngology specific database has added utility when compared with already available national ambulatory databases. PMID- 27371628 TI - A structured approach to hypotheses involving continuous exposures over the life course. AB - BACKGROUND: Epidemiologists are often interested in examining different hypotheses for how exposures measured repeatedly over the life course relate to later-life outcomes. A structured approach for selecting the hypotheses most supported by theory and observed data has been developed for binary exposures. The aim of this paper is to extend this to include continuous exposures and allow for confounding and missing data. METHODS: We studied two examples, the association between: (i) maternal weight during pregnancy and birthweight; and (ii) stressful family events throughout childhood and depression in adolescence. In each example we considered several plausible hypotheses including accumulation, critical periods, sensitive periods, change and effect modification. We used least angle regression to select the hypothesis that explained the most variation in the outcome, demonstrating appropriate methods for adjusting for confounders and dealing with missing data. RESULTS: The structured approach identified a combination of sensitive periods: pre-pregnancy weight, and gestational weight gain 0-20 weeks and 20-40 weeks, as the best explanation for variation in birthweight after adjusting for maternal height. A sensitive period hypothesis best explained variation in adolescent depression, with the association strengthening with the proximity of stressful family events. For each example, these models have theoretical support at least as strong as any competing hypothesis. CONCLUSIONS: We have extended the structured approach to incorporate continuous exposures, confounding and missing data. This approach can be used in either an exploratory or a confirmatory setting. The interpretation, plausibility and consistency with causal assumptions should all be considered when proposing and choosing life course hypotheses. PMID- 27371629 TI - 'Because it's the wife who has to look after the man': A descriptive qualitative study of older women and the intersection of gender and the provision of family caregiving at the end of life. AB - BACKGROUND: Research indicates that women are the primary family caregivers for others at life's end and, because of ageing populations, will keep fulfilling this role as they age. Yet, little is known about how the gendered nature of caregiving contributes to older women's understandings of providing care. AIM: To explore how gender norms constructed older women's views about the appropriate roles of women and men in providing palliative and end-of-life care for family members. DESIGN: Six focus groups were conducted with 39 community dwelling older adults (36 women and 3 men) using two vignettes to prompt discussion about experience of end of life caring and attitudes towards Advance Care Planning. This article reports on data gathered from female participants' reactions to Vignette 1 which prompted significant discussion regarding the intersection of gender and older women's caregiving experience. SETTING/PARTICIPANTS: A total of 36 women in the age ranges of '50-59 years' through to '90-99 years' from New Zealand. RESULTS: Three themes regarding gender and caregiving were identified: the expectation women will care, women's duty to care and women's construction of men in relation to caregiving and illness. The women adhered to stereotypical gender norms that regard women as primary caregivers. There was little connection between the burden they associated with caregiving and this gender construction. CONCLUSION: The expectation that older women will provide end-of-life care even when experiencing considerable burden is an unacknowledged outcome of gender norms that construct women as caregivers. PMID- 27371631 TI - Ibrutinib Inhibits VLA-4-Dependent Adhesion in CLL-Letter. PMID- 27371632 TI - Ibrutinib Inhibits VLA-4-Dependent Adhesion in CLL-Reply. PMID- 27371633 TI - Molecular Profile and FDG-PET Metabolic Volume at Staging in DLBCL-Letter. PMID- 27371634 TI - Molecular Profile and FDG-PET Metabolic Volume at Staging in DLBCL-Response. PMID- 27371635 TI - miR-10b expression in breast cancer stem cells supports self-renewal through negative PTEN regulation and sustained AKT activation. PMID- 27371636 TI - Intellectual disability-associated dBRWD3 regulates gene expression through inhibition of HIRA/YEM-mediated chromatin deposition of histone H3.3. PMID- 27371637 TI - Effect of Implicit Perceptual-Motor Training on Decision-Making Skills and Underpinning Gaze Behavior in Combat Athletes. AB - This study investigated the effect of a 12-session, implicit perceptual-motor training program on decision-making skills and visual search behavior of highly skilled junior female karate fighters (M age = 15.7 years, SD = 1.2). Eighteen participants were required to make (physical or verbal) reaction decisions to various attacks within different fighting scenarios. Fighters' performance and eye movements were assessed before and after the intervention, and during acquisition through the use of video-based and on-mat decision-making tests. The video-based test revealed that following training, only the implicit perceptual motor group (n = 6) improved their decision-making accuracy significantly compared to a matched motor training (placebo, n = 6) group and a control group (n = 6). Further, the implicit training group significantly changed their visual search behavior by focusing on fewer locations for longer durations. In addition, the session-by-session analysis showed no significant improvement in decision accuracy between training session 1 and all the other sessions, except the last one. Coaches should devote more practice time to implicit learning approaches during perceptual-motor training program to achieve significant decision-making improvements and more efficient visual search strategy with elite athletes. PMID- 27371638 TI - Computer-Detected Attention Affects Foreign Language Listening but Not Reading Performance. AB - No quantitative study has explored the influence of attention on learning English as a foreign language (EFL). This study investigated whether computer-detected attention is associated with EFL reading and listening and reading and listening anxiety. Traditional paper-based English tests used as entrance examinations and tests of general trait anxiety, reading, listening, reading test state anxiety, and listening test state anxiety were administered in 252 Taiwan EFL college students who were divided into High Attention (Conners' Continuous Performance Test, CPT < 50) and Low Attention (CPT >= 50) groups. No differences were found between the two groups for traditional paper-based English tests, trait anxieties, general English reading anxiety scales, and general English listening anxiety scales. The Low Attention group had higher test state anxiety and lower listening test scores than the High Attention group, but not in reading. State anxiety during listening tests for EFL students with computer-detected low attention tendency was elevated and their EFL listening performance was affected, but those differences were not found in reading. PMID- 27371639 TI - ADDENDUM: T Cells Expressing CD19/CD20 Bispecific Chimeric Antigen Receptors Prevent Antigen Escape by Malignant B Cells. PMID- 27371640 TI - Battling With Child Health and Nutrition in Southeast Asia. PMID- 27371641 TI - Management of critical illness with non-invasive ventilation by an Australian HEMS. AB - BACKGROUND: Non-invasive ventilation (NIV) therapy is widely used for the management of acute respiratory failure. The objective of this study was to investigate the current use of NIV during interhospital retrievals in an Australian physician-led aeromedical service. METHODS: We reviewed patients receiving NIV during interhospital retrieval at the Greater Sydney Area Helicopter Medical Services (GSA-HEMS) over a 14-month period. The main objectives were to describe the number of retrievals using NIV, the need for intubation in NIV patients and the effect of the therapy on mission duration. RESULTS: Over the study period, 3018 missions were reported; 106 cases (3.51%) involved administration of NIV therapy during the retrieval. The most common indication for NIV was pneumonia (34.0%). 86/106 patients received a successful trial of NIV therapy prior to interhospital transfer. 58 patients were transferred on NIV, while 28 patients had NIV removed during transport. None of these 86 patients required intubation or died, although 17/86 ultimately required intubation within 24 hours at the receiving centre. 20/106 patients required intubation at the referring hospital after a failed trial of NIV therapy. NIV was successfully used in all available transport platforms including rotary wing. Patients receiving NIV were found to have prolonged mission durations compared with other GSA-HEMS patients (222.5 vs 193 min). This increase in mission duration was largely attributable to NIV failure, resulting in a need for Rapid Sequence Intubation at the referring hospital. CONCLUSIONS: With careful patient selection, the use of interhospital NIV is feasible and appears to be safe in a retrieval system with care provided by a critical care physician. PMID- 27371642 TI - The use of the International Classification of Functioning, Disability and Health to classify the factors influencing mobility reported by persons with an amputation: An international study. AB - BACKGROUND: Amputation of lower limb results in limitations in mobility which are amenable to multiple rehabilitation interventions. The challenges faced by the persons with lower limb amputation vary internationally. The International Classification of Functioning, Disability and Health provides a common language to describe the function of persons with lower limb amputation across various countries. OBJECTIVES: This article reports the concepts in mobility important to persons with lower limb amputation across six countries using the International Classification of Functioning, Disability and Health. STUDY DESIGN: Qualitative study using focus groups and individual interviews. METHODS: Focus groups and individual interviews of persons with lower limb amputation were organised across six countries to identify the issues faced by patients with an amputation during and after their amputation, subsequent rehabilitation and on an ongoing basis in their daily life. Meaningful concepts were extracted from the responses and linked to suitable second-level and where applicable third-level International Classification of Functioning, Disability and Health categories. International Classification of Functioning, Disability and Health categorical frequencies were analysed to represent the prevalence and spread of International Classification of Functioning, Disability and Health categories by location. RESULTS: A total of 133 patients were interviewed. A large percentage (93%) of the identified concepts could be matched to International Classification of Functioning, Disability and Health categories for quantitative analysis. CONCLUSION: The important concepts in mobility were similar across different countries. The comprehensiveness of International Classification of Functioning, Disability and Health as a classification system for human function and its universality across the globe is demonstrated by the large proportion of the concepts contained in the interviews from across the study centres that could be matched to International Classification of Functioning, Disability and Health categories. Clinical relevance The activity and participation restrictions faced by a person with lower limb amputation vary internationally and are amenable to multiple rehabilitation interventions. The International Classification of Functioning, Disability and Health may provide a common language to report and quantify the various concepts important to the patient in their rehabilitation journey. PMID- 27371643 TI - A New Method for Determining the Optical Constants of Highly Transparent Solids. AB - Highly transparent substrates are of interest for a variety of applications, but it is difficult to measure their optical constants precisely, especially the absorption index in the transparent spectral region. In this paper, a combination technique (DOPTM-EM) using both the double optical pathlength transmission method (DOPTM) and the ellipsometry method (EM) is presented to obtain the optical constants of highly transparent substrates, which overcomes the deficiencies of both the two methods. The EM cannot give accurate result of optical constants when the absorption index is very weak. The DOPTM is suitable to retrieve the weak absorption index; however, two sets of solutions exist for the retrieved refractive index and absorption index, and only one is the true value that needs to be identified. In the DOPTM-EM, the optical constants are measured first by using the EM and set as the initial value in the gradient-based inverse method used in the DOPTM, which ensures only the true optical constants are retrieved. The new method simultaneously obtains the refractive index and the absorption index of highly transparent substrate without relying on the Kramers-Kronig relation. The optical constants of three highly transparent substrates (polycrystalline BaF2, CaF2, and MgF2) were experimentally determined within wavelength range from ultraviolet to infrared regions (0.2-14 um). The presented method will facilitate the measurement of optical constants for highly transparent materials. PMID- 27371644 TI - In Small We Trust: Lay Theories About Small and Large Groups. AB - Day-to-day interactions often involve individuals interacting with groups, but little is known about the criteria that people use to decide which groups to approach or trust and which to avoid or distrust. Seven studies provide evidence for a "small = trustworthy" heuristic, such that people perceive numerically smaller groups as more benevolent in their character and intentions. As a result of this, individuals in trust-sensitive contexts are more likely to approach and engage with groups that are relatively small than those that are relatively large. We provide evidence for this notion across a range of contexts, including analyses of social categories (Studies 1 and 2), ad hoc collections of individuals (Study 3), interacting panels (Studies 4-6), and generalized, abstract judgments (Study 7). Findings suggest the existence of a general lay theory of group size that may influence how individuals interact with groups. PMID- 27371645 TI - Quantifying Disease in Challenging Conditions: Incidence and Prevalence of Rheumatoid Arthritis. PMID- 27371646 TI - Qualitative Methods in Systemic Sclerosis Research. PMID- 27371647 TI - Clinical Usefulness of 18F-fluorodeoxyglucose Positron Emission Tomography for Enthesitis-related Arthritis Diagnosis. PMID- 27371648 TI - Early Onset of Chronic Rheumatic Disease May Lead to Creative Expression: The Stories of Antoni Gaudi and Maud Lewis. PMID- 27371649 TI - Cell Membrane-bound TLR2 and TLR4: Potential Predictors of Active Systemic Lupus Erythematosus and Lupus Nephritis. PMID- 27371650 TI - Canakinumab for Childhood Sight-threatening Refractory Uveitis: A Case Series. PMID- 27371651 TI - Occurrence of Rheumatoid Arthritis in a Patient Treated with Anakinra for Schnitzler Syndrome: A Case Report. PMID- 27371652 TI - Severe Rheumatoid Arthritis Developing in Conjunction with Gorlin Syndrome. PMID- 27371654 TI - NLRP3 A439V Mutation in a Large Family with Cryopyrin-associated Periodic Syndrome: Description of Ophthalmologic Symptoms in Correlation with Other Organ Symptoms. PMID- 27371653 TI - Severe Sensory Neuronopathy in Primary Sjogren Syndrome Resulting in Charcot Arthropathy. PMID- 27371657 TI - Clostridium Sordellii as an Uncommon Cause of Fatal Toxic Shock Syndrome in a Postpartum 33-Year-Old Asian Woman, and the Need for Antepartum Screening for This Clostridia Species in the General Female Population. AB - Clostridium sordellii (C. sordellii) is an anaerobic gram-positive rod most commonly found in the soil and sewage but also as part of the normal flora of the gastrointestinal tract and vagina of a small percentage of healthy individuals. C. sordellii infection is considered to result from childbirth, abortion, and/or gynecological procedures. Although many strains of C. sordellii are nonpathogenic, virulent toxin-producing strains exist. Infection with this organism typically manifests as a patient experiencing septic shock rapidly followed by end-organ failure. Identification of C. sordelli has been successful by traditional culture, mass spectrometry methods, and via molecular methods. Herein, we present a fatal case of C. sordellii infection of a postpartum 33-year old Asian woman. The organism was isolated by culture and identified using matrix assisted laser desorption/ionization-time-of-flight (MALDI-TOF) technology. With the advent of rapid detection methods, antepartum screening for the fatal Clostridium species should be implemented in the general female population. PMID- 27371658 TI - Workplace violence against medical staff in healthcare facilities in Barbados. AB - BACKGROUND: Anecdotal evidence suggests increasing workplace violence against healthcare workers in the Caribbean, but the prevalence is largely undocumented. AIMS: To determine the prevalence of workplace violence reported by medical staff at primary care clinics in Barbados. METHODS: A study utilizing a modified version of the standard World Health Organization Workplace Violence Questionnaire, designed to assess the incidence, types and features of workplace violence. All nursing and physician staff on duty at the island's eight primary care clinics during the study period were invited to participate. RESULTS: Of the 102 respondents (72% response rate), 63% of nursing and physician staff at the polyclinics in Barbados reported at least one episode of violence in the past year. The majority reported being exposed to verbal abuse (60%) and 19% reported being exposed to bullying. Seven percent of the staff reported incidents of sexual harassment, 3% physical violence and another 3% reported racial harassment. Patients emerged as the main perpetrators of violence (64%). Logistic regression showed statistically significant associations between gender and workplace violence. Females and nurses were more predisposed to experience violent incidents than males and physicians. CONCLUSIONS: Over a half of medical staff surveyed reported experiencing some type of violence in the past year, female gender being a significant predictor of abuse. Adequate documentation and implementing clear policies and violence prevention programmes in health institutions are crucial steps towards addressing this issue. PMID- 27371660 TI - Smart detection of atrial fibrillation?. AB - Aims: Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice, and its paroxysmal nature makes its detection challenging. In this trial, we evaluated a novel App for its accuracy to differentiate between patients in AF and patients in sinus rhythm (SR) using the plethysmographic sensor of an iPhone 4S and the integrated LED only. Methods and results: For signal acquisition, we used an iPhone 4S, positioned with the camera lens and LED light on the index fingertip. A 5 min video file was recorded with the pulse wave extracted from the green light spectrum of the signal. RR intervals were automatically identified. For discrimination between AF and SR, we tested three different statistical methods. Normalized root mean square of successive difference of RR intervals (nRMSSD), Shannon entropy (ShE), and SD1/SD2 index extracted from a Poincare plot. Eighty patients were included in the study (40 patients in AF and 40 patients in SR at the time of examination). For discrimination between AF and SR, ShE yielded the highest sensitivity and specificity with 85 and 95%, respectively. Applying a tachogram filter resulted in an improved sensitivity of 87.5%, when combining ShE and nRMSSD, while specificity remained stable at 95%. A combination of SD1/SD2 index and nRMSSD led to further improvement and resulted in a sensitivity and specificity of 95%. Conclusion: The algorithm tested reliably discriminated between SR and AF based on pulse wave signals from a smartphone camera only. Implementation of this algorithm into a smartwatch is the next logical step. PMID- 27371661 TI - Successful retrieval of an active fixation leadless pacemaker in a 74-year-old woman 506 days post-implant. PMID- 27371659 TI - Histone and DNA Modifications as Regulators of Neuronal Development and Function. AB - DNA and histone modifications, together with constraints imposed by nuclear architecture, contribute to the transcriptional regulatory landscape of the nervous system. Here, we provide select examples showing how these regulatory layers, often referred to as epigenetic, contribute to neuronal differentiation and function. We describe the interplay between DNA methylation and Polycomb mediated repression during neuronal differentiation, the role of DNA methylation and long-range enhancer-promoter interactions in Protocadherin promoter choice, and the contribution of heterochromatic silencing and nuclear organization in singular olfactory receptor expression. Finally, we explain how the activity dependent expression of a histone variant determines the longevity of olfactory sensory neurons. PMID- 27371662 TI - Relationship between cumulative exposure to 1,2-dichloropropane and incidence risk of cholangiocarcinoma among offset printing workers. AB - OBJECTIVES: This study aimed to evaluate the relationship between cumulative exposure to 1,2-dichloropropane (1,2-DCP) and incidence risk of cholangiocarcinoma among workers in the offset proof-printing section of a small printing company in Osaka, Japan. METHODS: We identified 95 workers of a printing company (78 men and 17 women) who had been exposed to 1,2-DCP between 1987 and 2006, and calculated the standardised incidence ratio (SIR) of cholangiocarcinoma from 1987 to 2012. We estimated cumulative exposure to 1,2-DCP and calculated SIRs in four exposure categories. We also calculated incidence rate ratios (RRs) adjusted by sex, age, calendar year and dichloromethane (DCM) exposure for three exposure categories using Poisson regression analysis. RESULTS: Cumulative exposures to 1,2-DCP ranged from 32 to 3433 ppm-years (mean, 851 ppm-years) and the SIR was 1171 (95% CI 682 to 1875). In the analysis of the four exposure categories, SIRs increased significantly in the three highest exposure categories, but not in the lowest category. Adjusted RRs in the middle and high exposure categories were 14.9 (95% CI 4.1 to 54.3) and 17.1 (95% CI 3.8 to 76.2), respectively, in the analysis without lag time, and were 11.4 (95% CI 3.3 to 39.6) and 32.4 (95% CI 6.4 to 163.9), respectively, in the analysis with a 5-year lag. The trend analysis revealed a significant increase in RR in association with increasing cumulative exposure to 1,2-DCP. DCM exposure was not significantly associated with the development of cholangiocarcinoma. CONCLUSIONS: The present study demonstrated an exposure-response relationship between exposure to 1,2-DCP and the development of cholangiocarcinoma. PMID- 27371664 TI - 'Should we consider renaming 'Mesoamerican Nephropathy' as Nephropathy of Unknown Cause in Agricultural Labourers (NUCAL)?' PMID- 27371663 TI - Atrazine in public water supplies and risk of ovarian cancer among postmenopausal women in the Iowa Women's Health Study. AB - BACKGROUND: Few studies have evaluated environmental chemical exposures in relation to ovarian cancer. We previously found an increased risk of ovarian cancer among postmenopausal women in Iowa associated with higher nitrate levels in public water supplies (PWS). However, elevated nitrate levels may reflect the presence of other agricultural chemicals, such as atrazine, one of the most commonly detected pesticides in Iowa PWS. METHODS: We evaluated the association between atrazine in drinking water and incident ovarian cancer (N=145, 1986-2010) among 13 041 postmenopausal women in the Iowa Women's Health Study who used their PWS for >=11 years as reported in 1989. Average levels of atrazine (1986-1987), nitrate-nitrogen (NO3-N, 1955-1988) and estimated levels of total trihalomethanes (TTHM, 1955-1988) from PWS monitoring data were linked to the participants' cities of residence. We computed HRs and 95% CIs by categories of the average atrazine level (not detected, <= or >0.37 parts per billion=median) using Cox proportional hazards regression adjusting for ovarian cancer risk factors. RESULTS: Atrazine was detected in water samples from 69 cities where 4155 women (32%) lived and levels were moderately correlated with NO3-N (rho=0.35) and TTHM (rho=0.24). Atrazine levels were not associated with ovarian cancer risk with or without adjusting for NO3-N and TTHM levels (p-trend=0.50 and 0.81, respectively). Further, there was no evidence for effect modification of the atrazine association by NO3-N or TTHM levels. CONCLUSIONS: In our study with low atrazine detection rates, we found no association between atrazine in PWS and postmenopausal ovarian cancer risk. PMID- 27371665 TI - Childhood placement in out-of-home care in relation to psychosocial outcomes in adults with fetal alcohol syndrome. AB - BACKGROUND: Even in adulthood, the disabilities associated with fetal alcohol spectrum disorders (FASD) may have a major impact on life, but different environmental circumstances during childhood may also be influential. This study aimed to investigate placements in out-of-home care, and number of early separations from caregivers, related to psychosocial outcomes in adults with fetal alcohol syndrome (FAS). Additional analyses were then done on a subgroup's cognitive development and mental health. METHODS: Data on education and living with biological parents or in out-of-home care were obtained from childhood medical records on 51 adults (43% women), mean age 32, all diagnosed with FAS. Adult psychosocial outcomes (e.g. highest completed education, economic status, care due to alcohol or illicit drug abuse, mental health and conviction for crime) were obtained from national registers. RESULTS: No significant within group differences related to the adult psychosocial outcomes were found. Psychiatric disorders, psychotropic drug prescriptions and crime convictions were equally common, regardless of whether placement in care was early or late, or whether the participants had experienced few or many early separations. CONCLUSIONS: We suggest that the findings illustrate the heterogeneity among individuals with FASD. Welfare authorities' decisions concerning special education and placement in out-of-home care should be tailored to each individual. Interventions from society are still needed for individuals with FAS over 22 years old. PMID- 27371666 TI - Patterns of life expectancy before and during economic recession, 2003-12: a European regions panel approach. AB - BACKGROUND: Previous research has reported a decrease in all-cause mortality during times of economic recession. Our objective was to identify the short-term effects of the current Great Recession on life expectancy at birth in Europe, and the role of social protection typology, income and gender. METHODS: We used a pooled time series cross-sectional design, with 232 European regions (level 2 of the Nomenclature of Territorial Units for Statistics) as the unit of analysis over 10 years (2003-12). The dependent variable was life expectancy at birth, and the independent variable was unemployment rate. We fit a model in first differences for the periods before and during the Great Recession (2003-07 and 2008-12, respectively), and stratified by sex, social protection typology (Eastern, Mediterranean and Northern) and regional income per capita RESULTS: We observed a negative association during the Great Recession between life expectancy (in years) and in unit change in unemployment among men and women in low-income Mediterranean regions [-0.048(95%CI: -0.081,-0.014) and -0.050(95%CI: 0.091,-0.007), respectively] but no change in trend, and a change in trend to a non-significant negative association among men in high-income Mediterranean and Northern regions (P = 0.005 and P = 0.002, respectively). We also observed a positive association among men in middle-income Mediterranean regions [0.044 (95%CI:0.004,0.084)], with change in trend (P = 0.047), and Eastern regions [0.042 (95%CI:0.001,0.072)] without change in trend. CONCLUSION: Overall, our data do not support the notion that increased life expectancy is associated with unemployment during the Great Recession. PMID- 27371667 TI - Ethnic differences in sleep duration at 5 years, and its relationship with overweight and blood pressure. AB - BACKGROUND: Studies on adult population indicate shorter sleep duration in ethnic minority groups than host populations. We examined ethnic differences in sleep duration and its relationship with overweight and blood pressure (BP) among children living in Amsterdam. METHODS: Participants include 2384 children (aged 5 years) and their mothers from the Amsterdam-based longitudinal study. Sleep was categorised into short sleep (<10 h/night) and normal sleep (10-11 h/night). Linear regressions ( Beta: were used to study association between sleep duration and systolic BP (SBP) and diastolic BP (DBP). Prevalence ratios (PRs) were used to study ethnic differences in sleep duration and its association with overweight and raised BP. RESULTS: Minority groups reported shorter sleep duration compared to native Dutch, with prevalence ranging from 11.3% in Dutch to 53.1% in Ghanaians. Age-adjusted PRs ranged from 3.38 (95%CI 2.63-4.34) in Moroccans to 4.78 (95%CI 3.36-6.82) in Ghanaian compared with Dutch children. Increased prevalence of overweight was observed among children with short sleep in Dutch and Moroccans only, but this risk was no longer statistically significant after further adjustment for socioeconomic status. Short sleep was not related to SBP and DBP in all groups. No relationship was observed between short sleep and raised BP except for African Surinamese (3.65, 95% CI 1.23-10.8). CONCLUSION: Like adults, children from ethnic minority populations sleep less hours than Dutch children. Efforts to improve ethnic inequalities in sleep hygiene should also include children at younger age. Associations as reported in adults with overweight and BP could not consistently be replicated in children, however. PMID- 27371668 TI - Health-based risk neutralization in private disability insurance. AB - BACKGROUND: Exclusions are used by insurers to neutralize higher than average risks of sickness absence (SA). However, differentiating risk groups according to one's medical situation can be seen as discrimination against people with health problems in violation of a 2006 United Nations convention. The objective of this study is to investigate whether the risk of SA of insured persons with exclusions added to their insurance contract differs from the risk of persons without exclusions. METHODS: A dynamic cohort of 15 632 applicants for private disability insurance at a company insuring only college and university educated self employed in the Netherlands. Mean follow-up was 8.94 years. Duration and number of SA periods were derived from insurance data to calculate the hazard of SA periods and of recurrence of SA periods. RESULTS: Self-employed with an exclusion added to their insurance policy experienced a higher hazard of one or more periods of SA and on average more SA days than self-employed without an exclusion. CONCLUSION: Persons with an exclusion had a higher risk of SA than persons without an exclusion. The question to what extent an individual should benefit from being less vulnerable to disease and SA must be addressed in a larger societal context, taking other aspects of health inequality and solidarity into account as well. PMID- 27371669 TI - Common Mechanisms Underlying Epileptogenesis and the Comorbidities of Epilepsy. AB - The importance of comorbidities in determining the quality of life of individuals with epilepsy and their families has received increasing attention in the past decade. Along with it has come a recognition that in some individuals, certain comorbidities may have preexisted, and may have contributed to their developing epilepsy. Many mechanisms are capable of interconnecting different dysfunctions that manifest as distinct disorders, often diagnosed and managed by different specialists. We review the human data from the perspective of epidemiology as well as insights gathered from neurodiagnostic and endocrine studies. Animal studies are reviewed to refine our mechanistic understanding of the connections, because they permit the narrowing of variables, which is not possible when studying humans. PMID- 27371670 TI - Regulation of Cellular Metabolism and Hypoxia by p53. AB - The p53 protein is essential for the implementation of the cellular response to challenging environmental conditions. Reacting to stochastic nutrient stress, p53 integrates the activity of key metabolite-sensing pathways to coordinate an appropriate cell response. During starvation, p53 activity augments cell survival pathways, inhibits unnecessary growth, and promotes efficient nutrient generation, utilization, and conservation. Similarly, during oxygen stress, p53 facilitates redirection of cellular metabolism toward energy generation through nonoxidative means, the suppression of reactive oxygen species (ROS) generation, and ROS detoxification-promoting cell survival. However, if adverse conditions are too acute or persistent, p53 can switch roles to implement canonical cell killing. The ability of p53 to regulate metabolism is a powerful feature of p53 biology that can both promote cell survival and act as a check on the inappropriate proliferation of cancer cells. PMID- 27371671 TI - MDMX (MDM4), a Promising Target for p53 Reactivation Therapy and Beyond. AB - The MDMX protein was identified as a p53-interacting protein with a strong similarity to MDM2. Like Mdm2, Mdmx expression is essential for curbing p53 activity during embryonic development, indicating nonredundant functions of Mdmx and Mdm2. There is now a large body of evidence indicating that cancers frequently up-regulate MDMX expression as a means to dampen p53 tumor-suppressor function. Importantly, MDMX also shows p53-independent oncogenic functions. These data make MDMX an attractive therapeutic target for cancer therapy. Here, we summarize the mechanisms used by cancer cells to increase MDMX expression and promising pharmacological strategies to target MDMX in cancer-in particular, the recent findings that antisense oligonucleotides (ASOs) can be used to efficiently modulate MDMX messenger RNA (mRNA) splicing. PMID- 27371672 TI - The Epilepsy Spectrum: Targeting Future Research Challenges. AB - There have been tremendous recent advances in our understanding of the biological underpinnings of epilepsy and associated comorbidities that justify its representation as a spectrum disorder. Advances in genetics, electrophysiology, and neuroimaging have greatly improved our ability to differentiate, diagnose, and treat individuals with epilepsy. However, we have made little overall progress in preventing epilepsy, and the number of patients who are cured remains small. Likewise, the comorbidities of epilepsy are often underdiagnosed or not adequately treated. In this article, we suggest a few areas in which additional research will likely pay big dividends for patients and their families. PMID- 27371674 TI - Biologic Approaches in Sports Medicine: Potential, Perils, and Paths Forward. PMID- 27371675 TI - Diagnostic Accuracy of Various Imaging Modalities for Suspected Lower Extremity Stress Fractures: Letter to the Editor. PMID- 27371673 TI - Association of Plasma DPP4 Activity With Mild Cognitive Impairment in Elderly Patients With Type 2 Diabetes: Results From the GDMD Study in China. AB - OBJECTIVE: Hyperglycemia, inflammation, and oxidative stress are thought to be involved in the pathogenesis of cognitive decline. Dipeptidyl peptidase-4 (DPP4) is a newly identified adipokine related to these risk factors. Hence, we aimed to investigate the association between plasma DPP4 activities and mild cognitive impairment (MCI) in elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We evaluated plasma DPP4 activity, inflammatory markers, and oxidative stress parameters in a cross-sectional sample of 1,160 patients with type 2 diabetes aged 60 years or older in China. MCI was diagnosed based on criteria established by the National Institute on Aging-Alzheimer's Association workgroups RESULTS: Patients in the highest quartile of DPP4 activity had higher HbA1c, interleukin 6 (IL-6), CRP, nitrotyrosine, 8-iso-PGF2a, and lower Montreal Cognitive Assessment (MoCA) scores compared with subjects in the lowest quartile (P < 0.001). In the highest DPP4 quartile, MCI risk was higher (odds ratio 3.49; 95% CI 1.97-4.57) than in the lowest quartile after adjustment for potential confounders. The risk for MCI increased more with higher levels of DPP4 activity, IL-6, CRP, nitrotyrosine, and 8-iso-PGF2a (P < 0.05), but not with higher levels of HbA1c. CONCLUSIONS: This study shows that increased DPP4 activities are independently associated with MCI in elderly patients with type 2 diabetes. The mechanisms might be partly explained by the effect of DPP4 on inflammation and oxidative stress. These observations raise further interest in DPP4 activity for its potential effect on these MCI-related risk factors as a biological marker or even a possible therapeutic target for MCI. PMID- 27371676 TI - Diagnostic Accuracy of Various Imaging Modalities for Suspected Lower Extremity Stress Fractures: Response. PMID- 27371677 TI - Could Isokinetic Evaluation Contribute to the Assessment of Sex Differences in the Incidence of ACL, MCL, and Meniscal Injuries in Collegiate and High School Sports? Letter to the Editor. PMID- 27371678 TI - Could Isokinetic Evaluation Contribute to the Assessment of Sex Differences in the Incidence of ACL, MCL, and Meniscal Injuries in Collegiate and High School Sports? Response. PMID- 27371679 TI - Corrigendum. AB - Dragoo JL, Wasterlain AS, Braun HJ, Nead KT. Platelet-rich plasma as a treatment for patellar tendinopathy: a double-blind, randomized controlled trial. Am J Sports Med. 2014;42(3):610-618. (Original DOI: 10.1177/0363546513518416). PMID- 27371680 TI - Pericapillary basement membrane thickening in human skeletal muscles. AB - The basement membrane (BM) surrounding capillaries in skeletal muscles varies physiologically in thickness according to age, physical fitness, and anatomical site in humans. Furthermore, the pericapillary BM thickness (CBMT) increases pathophysiologically during several common disease states, including peripheral arterial disease and diabetes mellitus. This review on CBM thickening in human skeletal muscles is two pronged. First, it addresses the advantages/disadvantages of grid- and tablet-based measuring and morphometric techniques that are implemented to assess the CBMT on transmission electron micrographs. Second, it deals with the biology of CBM thickening in skeletal muscles, particularly its possible causes, molecular mechanisms, and functional impact. CBM thickening is triggered by several physical factors, including diabetes-associated glycation, hydrostatic pressure, and inflammation. Increased biosynthesis of type IV collagen expression or repetitive cycles in pericyte or endothelial cell degeneration/proliferation appear to be most critical for CBM accumulation. A thickened CBM obviously poses a greater barrier for diffusion, lowers the microvascular elasticity, and impedes transcytosis of inflammatory cells. Our own morphometric data reveal the CBM enlargement to be not accompanied by the pericyte coverage. Owing to an overlap or redundancy in the capillary supply, CBM thickening in skeletal muscles might not be such a devastating occurrence as in organs with endarterial circulation (e.g., kidney and retina). CBM growth in skeletal muscles can be reversed by training or administration of antidiabetic drugs. In conclusion, CBM thickening in skeletal muscles is a microvascular remodeling process by which metabolic, hemodynamic, and inflammatory forces are integrated together and which could play a hitherto underestimated role in etiology/progression of human diseases. PMID- 27371681 TI - Pregnancy mitigates cardiac pathology in a mouse model of left ventricular pressure overload. AB - In Western countries heart disease is the leading cause of maternal death during pregnancy. The effect of pregnancy on the heart is difficult to study in patients with preexisting heart disease. Since experimental studies are scarce, we investigated the effect of pressure overload, produced by transverse aortic constriction (TAC) in mice, on the ability to conceive, pregnancy outcome, and maternal cardiac structure and function. Four weeks of TAC produced left ventricular (LV) hypertrophy and dysfunction with marked interstitial fibrosis, decreased capillary density, and induced pathological cardiac gene expression. Pregnancy increased relative LV and right ventricular weight without affecting the deterioration of LV function following TAC. Surprisingly, the TAC-induced increase in relative heart and lung weight was mitigated by pregnancy, which was accompanied by a trend towards normalization of capillary density and natriuretic peptide type A expression. Additionally, the combination of pregnancy and TAC increased the cardiac phosphorylation of c-Jun, and STAT1, but reduced phosphoinositide 3-kinase phosphorylation. Finally, TAC did not significantly affect conception rate, pregnancy duration, uterus size, litter size, and pup weight. In conclusion, we found that, rather than exacerbating the changes associated with cardiac pressure overload, pregnancy actually attenuated pathological LV remodeling and mitigated pulmonary congestion, and pathological gene expression produced by TAC, suggesting a positive effect of pregnancy on the pressure-overloaded heart. PMID- 27371682 TI - Ventricular stimulus site influences dynamic dispersion of repolarization in the intact human heart. AB - The spatial variation in restitution properties in relation to varying stimulus site is poorly defined. This study aimed to investigate the effect of varying stimulus site on apicobasal and transmural activation time (AT), action potential duration (APD) and repolarization time (RT) during restitution studies in the intact human heart. Ten patients with structurally normal hearts, undergoing clinical electrophysiology studies, were enrolled. Decapolar catheters were placed apex to base in the endocardial right ventricle (RVendo) and left ventricle (LVendo), and an LV branch of the coronary sinus (LVepi) for transmural recording. S1-S2 restitution protocols were performed pacing RVendo apex, LVendo base, and LVepi base. Overall, 725 restitution curves were analyzed, 74% of slopes had a maximum slope of activation recovery interval (ARI) restitution (Smax) > 1 (P < 0.001); mean Smax = 1.76. APD was shorter in the LVepi compared with LVendo, regardless of pacing site (30-ms difference during RVendo pacing, 25 ms during LVendo, and 48-ms during LVepi; 50th quantile, P < 0.01). Basal LVepi pacing resulted in a significant transmural gradient of RT (77 ms, 50th quantile: P < 0.01), due to loss of negative transmural AT-APD coupling (mean slope 0.63 +/ 0.3). No significant transmural gradient in RT was demonstrated during endocardial RV or LV pacing, with preserved negative transmural AT-APD coupling (mean slope -1.36 +/- 1.9 and -0.71 +/- 0.4, respectively). Steep ARI restitution slopes predominate in the normal ventricle and dynamic ARI; RT gradients exist that are modulated by the site of activation. Epicardial stimulation to initiate ventricular activation promotes significant transmural gradients of repolarization that could be proarrhythmic. PMID- 27371683 TI - Endogenous nitric oxide derived from NOS I or II in thoracic spinal cord exerts opposing tonic modulation on sympathetic vasomotor tone via disparate mechanisms in anesthetized rats. AB - The sympathetic preganglionic neurons (SPN) in the thoracic spinal cord regulate vasomotor tone via norepinephrine released from sympathetic terminals and adrenal medulla. We assessed the hypothesis that nitric oxide synthase I (NOS I)- and NOS II-derived nitric oxide (NO) in the thoracic spinal cord differentially modulate sympathetic outflow and that the adrenal medulla may be involved in those modulatory actions. In Sprague-Dawley rats, NOS I immunoreactivity was distributed primarily in the perikaryon, proximal dendrites, or axons of SPN, and small clusters of NOS II immunoreactivity impinged mainly on the circumference of SPN. Intrathecal administration of 7-nitroindazole (7-NI), a specific NOS I antagonist, into the thoracic spinal cord significantly reduced arterial pressure, heart rate, and basal or baroreflex-mediated sympathetic vasomotor tone. On the other hand, intrathecal application of S-methylisothiourea (SMT), a specific NOS II antagonist, elevated arterial pressure with a transient reduction of heart rate, induced a surge of plasma norepinephrine, and reduced baroreflex mediated but not basal sympathetic vasomotor tone. Bilateral adrenalectomy significantly exacerbated the cardiovascular responses to 7-NI but antagonized those to SMT. We conclude that both NOS I and NOS II are present in the thoracic spinal cord and are tonically active under physiological conditions. Furthermore, the endogenous NO generated by NOS I-containing SPN exerts a tonic excitatory action on vasomotor tone mediated by norepinephrine released from the adrenal medulla and sympathetic nerve terminals. On the other hand, NO derived from NOS II exerts a tonic inhibitory action on sympathetic outflow from the SPN that targets primarily the blood vessels. PMID- 27371684 TI - Sympathetic neural reactivity to mental stress in offspring of hypertensive parents: 20 years revisited. AB - A number of recent studies have highlighted large interindividual variability of muscle sympathetic nerve activity (MSNA) responsiveness to mental stress in humans. The purpose of this study was to examine blood pressure (BP) and MSNA responsiveness to mental stress in a large and generalizable cohort of young adults with and without family history of hypertension (FHH). We hypothesized that subjects with FHH would demonstrate greater sympathoexcitation to mental stress than subjects without FHH. A total of 87 subjects (55 men and 32 women, 18 40 yr of age) from recently published (n = 45) and ongoing (n = 42) studies were examined; 57 subjects (19 with FHH and 38 without FHH) had complete MSNA recordings at baseline. Heart rate (HR), BP, and MSNA were recorded during 5 min of supine rest and 5 min of mental stress (mental arithmetic). Resting MSNA and HR were not statistically different between subjects with and without FHH (P > 0.05), whereas resting mean arterial pressure was higher in subjects with FHH (86 +/- 2 vs. 80 +/- 1 mmHg, P < 0.05). Mental stress increased MSNA in subjects with FHH (Delta5 +/- 1 bursts/min), but not in subjects without FHH [Delta1 +/- 1 burst/min, P < 0.01 (time * group)]. Mental stress increased mean arterial pressure (Delta12 +/- 1 and Delta10 +/- 1 mmHg, P < 0.001) and HR (Delta19 +/- 2 and Delta16 +/- 2 beats/min, P < 0.001) in subjects with and without FHH, but these increases were not different between groups [P >= 0.05 (time * group)]. MSNA and BP reactivity to mental stress were not correlated in either group. In conclusion, FHH was associated with heightened MSNA reactivity to mental stress, despite a dissociation between MSNA and BP responsiveness. PMID- 27371686 TI - Functional assessment of the stenotic carotid artery by CFD-based pressure gradient evaluation. AB - The functional assessment of a hemodynamic significant stenosis base on blood pressure variation has been applied for evaluation of the myocardial ischemic event. This functional assessment shows great potential for improving the accuracy of the classification of the severity of carotid stenosis. To explore the value of grading the stenosis using a pressure gradient (PG)-we had reconstructed patient-specific carotid geometries based on MRI images computational fluid dynamics were performed to analyze the PG in their stenotic arteries. Doppler ultrasound image data and the corresponding MRI image data of 19 patients with carotid stenosis were collected. Based on these, 31 stenotic carotid arterial geometries were reconstructed. A combinatorial boundary condition method was implemented for steady-state computer fluid dynamics simulations. Anatomic parameters, including tortuosity (T), the angle of bifurcation, and the cross-sectional area of the remaining lumen, were collected to investigate the effect on the pressure distribution. The PG is highly correlated with the severe stenosis (r = 0.902), whereas generally, the T and the angle of the bifurcation negatively correlate to the pressure drop of the internal carotid artery stenosis. The calculation required <10 min/case, which made it prepared for the fast diagnosis of the severe stenosis. According to the results, we had proposed a potential threshold value for distinguishing severe stenosis from mild-moderate stenosis (PG = 0.88). In conclusion, the PG could serve as the additional factor for improving the accuracy of grading the severity of the stenosis. PMID- 27371685 TI - Selective serotonin reuptake inhibitor exposure constricts the mouse ductus arteriosus in utero. AB - Use of selective serotonin reuptake inhibitors (SSRIs) is common during pregnancy. Fetal exposure to SSRIs is associated with persistent pulmonary hypertension of the newborn (PPHN); however, a direct link between the two has yet to be established. Conversely, it is well known that PPHN can be caused by premature constriction of the ductus arteriosus (DA), a fetal vessel connecting the pulmonary and systemic circulations. We hypothesized that SSRIs could induce in utero DA constriction. Using isolated vessels and whole-animal models, we sought to determine the effects of two commonly prescribed SSRIs, fluoxetine and sertraline, on the fetal mouse DA. Cannulated vessel myography studies demonstrated that SSRIs caused concentration-dependent DA constriction and made vessels less sensitive to prostaglandin-induced dilation. Moreover, in vivo studies showed that SSRI-exposed mice had inappropriate DA constriction in utero. Taken together, these findings establish that SSRIs promote fetal DA constriction and provide a potential mechanism by which SSRIs could contribute to PPHN. PMID- 27371687 TI - A gap junction inhibitor, carbenoxolone, induces spatiotemporal dispersion of renal cortical perfusion and impairs autoregulation. AB - Renal autoregulation dynamics originating from the myogenic response (MR) and tubuloglomerular feedback (TGF) can synchronize over large regions of the kidney surface, likely through gap junction-mediated electrotonic conduction and reflecting distributed operation of autoregulation. We tested the hypotheses that inhibition of gap junctions reduces spatial synchronization of autoregulation dynamics, abrogates spatial and temporal smoothing of renal perfusion, and impairs renal autoregulation. In male Long-Evans rats, we infused the gap junction inhibitor carbenoxolone (CBX) or the related glycyrrhizic acid (GZA) that does not block gap junctions into the renal artery and monitored renal blood flow (RBF) and surface perfusion by laser speckle contrast imaging. Neither CBX nor GZA altered RBF or mean surface perfusion. CBX preferentially increased spatial and temporal variation in the distribution of surface perfusion, increased spatial variation in the operating frequencies of the MR and TGF, and reduced phase coherence of TGF and increased its dispersion. CBX, but not GZA, impaired dynamic and steady-state autoregulation. Separately, infusion of the Rho kinase inhibitor Y-27632 paralyzed smooth muscle, grossly impaired dynamic autoregulation, and monotonically increased spatial variation of surface perfusion. These data suggest CBX inhibited gap junction communication, which in turn reduced the ability of TGF to synchronize among groups of nephrons. The results indicate that impaired autoregulation resulted from degraded synchronization, rather than the reverse. We show that network behavior in the renal vasculature is necessary for effective RBF autoregulation. PMID- 27371688 TI - The adipokine chemerin amplifies electrical field-stimulated contraction in the isolated rat superior mesenteric artery. AB - The adipokine chemerin causes arterial contraction and is implicated in blood pressure regulation, especially in obese subjects with elevated levels of circulating chemerin. Because chemerin is expressed in the perivascular adipose tissue (PVAT) that surrounds the sympathetic innervation of the blood vessel, we tested the hypothesis that chemerin (endogenous and exogenous) amplifies the sympathetic nervous system in mediating electrical field-stimulated (EFS) contraction. The superior mesenteric artery, with or without PVAT and with endothelium and sympathetic nerve intact, was mounted into isolated tissue baths and used for isometric contraction and stimulation. Immunohistochemistry validated a robust expression of chemerin in the PVAT surrounding the superior mesenteric artery. EFS (0.3-20 Hz) caused a frequency-dependent contraction in isolated arteries that was reduced by the chemerin receptor ChemR23 antagonist CCX832 alone (100 nM; with, but not without, PVAT), but not by the inactive congener CCX826 (100 nM). Exogenous chemerin-9 (1 MUM)-amplified EFS-induced contraction in arteries (with and without PVAT) was blocked by CCX832 and the alpha-adrenergic receptor antagonist prazosin. CCX832 did not directly inhibit, nor did chemerin directly amplify, norepinephrine-induced contraction. Whole mount immunohistochemical experiments support colocalization of ChemR23 with the sympathetic nerve marker tyrosine hydroxylase in superior mesenteric PVAT and, to a lesser extent, in arteries and veins. These studies support the idea that exogenous chemerin modifies sympathetic nerve-mediated contraction through ChemR23 and that ChemR23 may be endogenously activated. This is significant because of the well-appreciated role of the sympathetic nervous system in blood pressure control. PMID- 27371690 TI - The TIDieR Checklist Will Benefit the Physical Therapy Profession. PMID- 27371689 TI - Estimation of the Effect of the Predator Scytodes globula (Araneae: Scytodidae) on Loxosceles laeta (Araneae: Sicariidae) Populations. AB - It has been reported that Scytodes spiders are predators of spiders of the genus Loxosceles, but the question of the effect of Scytodes globula Nicolet on Loxosceles laeta (Nicolet) populations is still unanswered. The goal of this study is to analyze the population effect of S. globula on the population dynamics of L. laeta by means of simulation with projection matrices, considering the seasonal fluctuation of fecundity, random meetings between the predator and the prey, and limited growth of the L. laeta population. We found that the most important parameters to predict the characteristics of the population at equilibrium are the fertility and the survival function of the spider of advanced developmental stage. Also, the predator S. globula significantly decreases population size, population fluctuations, and the proportion of reproductive individuals of L. laeta The most probable effect of S. globula on L. laeta populations is a decrease of 20% of the population size. This is insufficient to consider this species as an agent of biological control of L. laeta However, the action of S. globula is not negligible because decreasing the L. laeta population by about 20% could mean a decrease of about 15% in the incidence of loxoscelism. This action is probably less effective than other epidemiological measures such as house cleaning and insecticides or arachnicides and probably similar to the direct action of humans eliminating one or two spiders per year in their houses, but it helps. PMID- 27371691 TI - Cochrane Physical and Rehabilitation Medicine: A New Field to Bridge Between Best Evidence and the Specific Needs of Our Field of Competence. PMID- 27371692 TI - The Single-Case Reporting Guideline In BEhavioural Interventions (SCRIBE) 2016 Statement. AB - We developed a reporting guideline to provide authors with guidance about what should be reported when writing a paper for publication in a scientific journal using a particular type of research design: the single-case experimental design. This report describes the methods used to develop the Single-Case Reporting guideline In BEhavioural interventions (SCRIBE) 2016. As a result of 2 online surveys and a 2-day meeting of experts, the SCRIBE 2016 checklist was developed, which is a set of 26 items that authors need to address when writing about single case research. This article complements the more detailed SCRIBE 2016 Explanation and Elaboration article (Tate et al., 2016) that provides a rationale for each of the items and examples of adequate reporting from the literature. Both these resources will assist authors to prepare reports of single-case research with clarity, completeness, accuracy, and transparency. They will also provide journal reviewers and editors with a practical checklist against which such reports may be critically evaluated. We recommend that the SCRIBE 2016 is used by authors preparing manuscripts describing single-case research for publication, as well as journal reviewers and editors who are evaluating such manuscripts. SCIENTIFIC ABSTRACT: Reporting guidelines, such as the Consolidated Standards of Reporting Trials (CONSORT) Statement, improve the reporting of research in the medical literature (Turner et al., 2012). Many such guidelines exist and the CONSORT Extension to Nonpharmacological Trials (Boutron et al., 2008) provides suitable guidance for reporting between-groups intervention studies in the behavioral sciences. The CONSORT Extension for N-of-1 Trials (CENT 2015) was developed for multiple crossover trials with single individuals in the medical sciences (Shamseer et al., 2015; Vohra et al., 2015), but there is no reporting guideline in the CONSORT tradition for single-case research used in the behavioral sciences. We developed the Single-Case Reporting guideline In BEhavioural interventions (SCRIBE) 2016 to meet this need. This Statement article describes the methodology of the development of the SCRIBE 2016, along with the outcome of 2 Delphi surveys and a consensus meeting of experts. We present the resulting 26 item SCRIBE 2016 checklist. The article complements the more detailed SCRIBE 2016 Explanation and Elaboration article (Tate et al., 2016) that provides a rationale for each of the items and examples of adequate reporting from the literature. Both these resources will assist authors to prepare reports of single-case research with clarity, completeness, accuracy, and transparency. They will also provide journal reviewers and editors with a practical checklist against which such reports may be critically evaluated. PMID- 27371694 TI - ERRATUM. PMID- 27371696 TI - The target of ACPA. PMID- 27371693 TI - Silicon enhances leaf remobilization of iron in cucumber under limited iron conditions. AB - BACKGROUND AND AIMS: Retranslocation of iron (Fe) from source tissues enhances plant tolerance to Fe deficiency. Previous work has shown that silicon (Si) can alleviate Fe deficiency by enhancing acquisition and root to shoot translocation of Fe. Here the role of Si in Fe mobilization in older leaves and the subsequent retranslocation of Fe to young leaves of cucumber (Cucumis sativus) plants growing under Fe-limiting conditions was investigated. METHODS: Iron ((57)Fe or naturally occurring isotopes) was measured in leaves at different positions on plants hydroponically growing with or without Si supply. In parallel, the concentration of the Fe chelator nicotianamine (NA) along with the expression of nicotianamine synthase (NAS) involved in its biosynthesis and the expression of yellow stripe-like (YSL) transcripts mediating Fe-NA transport were also determined. KEY RESULTS: In plants not receiving Si, approximately half of the total Fe content remained in the oldest leaf. In contrast, Si-treated plants showed an almost even Fe distribution among leaves with four different developmental stages, thus providing evidence of enhanced Fe remobilization from source leaves. This Si-stimulated Fe export was paralleled by an increased NA accumulation and expression of the YSL1 transporter for phloem loading/unloading of the Fe-NA complex. CONCLUSIONS: The results suggest that Si enhances remobilization of Fe from older to younger leaves by a more efficient NA-mediated Fe transport via the phloem. In addition, from this and previous work, a model is proposed of how Si acts to improve Fe homeostasis under Fe deficiency in cucumber. PMID- 27371697 TI - Vein inflammation and ultrasound in Behcet's syndrome. PMID- 27371698 TI - Long-term follow-up results of the multicenter phase II trial of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of standard tyrosine kinase inhibitor therapy. AB - BACKGROUND: This investigator-initiated trial provided the justification for the phase III GRID study resulting in worldwide regulatory approval of regorafenib as a third-line therapy for patients with metastatic gastrointestinal stromal tumors (GIST). We report the genotype analyses, long-term safety, and activity results from this initial trial of regorafenib in GIST. PATIENTS AND METHODS: The trial was conducted between February 2010 and January 2014, among adult patients with metastatic GIST, after failure of at least imatinib and sunitinib. Patients received regorafenib orally, 160 mg once daily, days 1-21 of a 28-day cycle. Clinical benefit rate (CBR), defined as complete or partial response (PR), or stable disease lasting >=16 weeks per RECIST 1.1, progression-free survival (PFS), overall survival (OS), long-term safety data, and metabolic response by functional imaging were assessed. RESULTS: Thirty-three patients received at least one dose of regorafenib. The median follow-up was 41 months. CBR was documented in 25 of 33 patients [76%; 95% confidence interval (CI) 58% to 89%], including six PRs. The median PFS was 13.2 months (95% CI 9.2-18.3 months) including four patients who remained progression-free at study closure, each achieving clinical benefit for more than 3 years (range 36.8-43.5 months). The median OS was 25 months (95% CI 13.2-39.1 months). Patients whose tumors harbored a KIT exon 11 mutation demonstrated the longest median PFS (13.4 months), whereas patients with KIT/PDGFRA wild-type, non-SDH-deficient tumors experienced a median 1.6 months PFS (P < 0.0001). Long-term safety profile is consistent with previous reports; hand-foot skin reaction and hypertension were the most common reasons for dose reduction. Notably, regorafenib induced objective responses and durable benefit in SDH-deficient GIST. CONCLUSIONS: Long-term follow-up of patients with metastatic GIST treated with regorafenib suggests particular benefit among patients with primary KIT exon 11 mutations and those with SDH-deficient GIST. Dose modifications are frequently required to manage treatment-related toxicities. CLINICAL TRIAL NUMBER: NCT01068769. PMID- 27371705 TI - ADEA Mission, Strategic Directions, and Key Priorities, 2015-18. PMID- 27371704 TI - Bylaws of the American Dental Education Association: (With changes approved by the 2016 House of Delegates). PMID- 27371706 TI - ADEA Staff (as of June 2016). PMID- 27371707 TI - The role of infrapatellar fat pad resection in total knee arthroplasty. PMID- 27371709 TI - Spatially-Optimized Sequential Sampling Plan for Cabbage Aphids Brevicoryne brassicae L. (Hemiptera: Aphididae) in Canola Fields. AB - The cabbage aphid is a significant pest worldwide in brassica crops, including canola. This pest has shown considerable ability to develop resistance to insecticides, so these should only be applied on a "when and where needed" basis. Thus, optimized sampling plans to accurately assess cabbage aphid densities are critically important to determine the potential need for pesticide applications. In this study, we developed a spatially optimized binomial sequential sampling plan for cabbage aphids in canola fields. Based on five sampled canola fields, sampling plans were developed using 0.1, 0.2, and 0.3 proportions of plants infested as action thresholds. Average sample numbers required to make a decision ranged from 10 to 25 plants. Decreasing acceptable error from 10 to 5% was not considered practically feasible, as it substantially increased the number of samples required to reach a decision. We determined the relationship between the proportions of canola plants infested and cabbage aphid densities per plant, and proposed a spatially optimized sequential sampling plan for cabbage aphids in canola fields, in which spatial features (i.e., edge effects) and optimization of sampling effort (i.e., sequential sampling) are combined. Two forms of stratification were performed to reduce spatial variability caused by edge effects and large field sizes. Spatially optimized sampling, starting at the edge of fields, reduced spatial variability and therefore increased the accuracy of infested plant density estimates. The proposed spatially optimized sampling plan may be used to spatially target insecticide applications, resulting in cost savings, insecticide resistance mitigation, conservation of natural enemies, and reduced environmental impact. PMID- 27371708 TI - Socioeconomic status inequalities in low-grade inflammation during childhood. AB - BACKGROUND: Family socioeconomic status (SES) is an important source of child health disparities in the USA. Chronic stress is one way SES may impact children's physiology with implications for later health inequalities. These processes may work differently across childhood due to differences in exposure and susceptibility to stressors at different ages. We assess associations between family SES and one biomarker of chronic stress exposure-low-grade inflammation detected by elevated C reactive protein (CRP)-and evaluate differences in the associations by child age. METHODS: We used nationally representative data from the National Health and Nutrition Examination Survey and Tobit regression models to estimate SES associations with CRP and the moderating effects of age for children age 2-18 years. Our sample was limited to CRP <=10 mg/l to focus on low grade inflammation (N=13 165). RESULTS: Children whose parent had less than a high school degree had 35% higher CRP than those with a college graduate parent; and, poor children had 24% higher CRP than those with high family income, net of controls. When children's body mass index was accounted for, low education and poverty associations were reduced to 19% and 15%, respectively. Child age interactions were negative and significant for both parental education and family income. CONCLUSIONS: This study provides new evidence that SES is associated with low-grade inflammation in children, and that these associations may be particularly strong during early and mid-childhood. Future research should further our understanding of stressors related to low family SES that may lead to immune system dysregulation during childhood. PMID- 27371710 TI - Supercooling Capacity and Cold Tolerance of the Wild Silkworm, Antheraea pernyi (Lepidoptera: Saturniidae). AB - While wild silkworms have served humans for several thousand years, little attention on cold hardiness has been paid to these economically important species. In the present study, supercooling capacity and low temperature tolerance of Chinese oak silkworm, Antheraea pernyi (Guerin-Meneville) (Lepidoptera: Saturniidae), an economic insect reared both for silk production as well as human food, were examined under laboratory conditions. The supercooling points (SCPs) of pupae dropped significantly from a mean of -15.6 degrees C in prediapause to -20.1 degrees C in diapause, and then increased to -17.5 degrees C during postdiapause development. Sex and voltinism influenced body mass but had no significant effect on the SCP. Our data demonstrated that cold tolerance of A. pernyi is tightly linked to life stage. Exposure of eggs to -5 degrees C for up to 8 h had no effect on the hatching rate, whereas silkworm larvae failed to break through the chorion and hatch following a 4-8-h exposure to -10 degrees C. Mean SCPs of intact eggs and naked larvae one day before hatching were similar, 23.3 degrees C and -22.3 degrees C, respectively, indicating that chorion does not significantly affect SCP. Comparison of lower lethal temperature (LLT50) and SCP means suggested that both pupae and eggs of A. pernyi are chill intolerant. These data will improve our understanding of low temperature tolerance in this commercially important species. PMID- 27371711 TI - Inhibition of Cathepsin B Alleviates Secondary Degeneration in Ipsilateral Thalamus After Focal Cerebral Infarction in Adult Rats. AB - Secondary degeneration in areas beyond ischemic foci can inhibit poststroke recovery. The cysteine protease Cathepsin B (CathB) regulates cell death and intracellular protein catabolism. To investigate the roles of CathB in the development of secondary degeneration in the ventroposterior nucleus (VPN) of the ipsilateral thalamus after focal cerebral infarction, infarct volumes, immunohistochemistry and immunofluorescence, and Western blotting analyses were conducted in a distal middle cerebral artery occlusion (dMCAO) stroke model in adult rats. We observed marked neuron loss and gliosis in the ipsilateral thalamus after dMCAO, and the expression of CathB and cleaved caspase-3 in the VPN was significantly upregulated; glial cells were the major source of CathB. Although it had no effect on infarct volume, delayed intracerebroventricular treatment with the membrane-permeable CathB inhibitor CA-074Me suppressed the expression of CathB and cleaved caspase-3 in ipsilateral VPN and accordingly alleviated the secondary degeneration. These data indicate that CathB mediates a novel mechanism of secondary degeneration in the VPN of the ipsilateral thalamus after focal cortical infarction and suggest that CathB might be a therapeutic target for the prevention of secondary degeneration in patients after stroke. PMID- 27371712 TI - Regulation of programmed cell death by phytoglobins. AB - Programmed cell death (PCD) is a fundamental plant process in growth and development and in response to both biotic and abiotic stresses. Nitric oxide (NO) is a central component in determining whether a cell undergoes PCD, either as a direct elicitor of the response or as a factor in signal transduction from various hormones. Both NO and hormones that use NO as a signal transducer are mobile in the plant. Why do one set of cells die while adjacent cells remain alive, if this is the case? There is evidence to suggest that phytoglobins (Pgbs; previously termed non-symbiotic hemoglobins) may act as binary switches to determine plant cellular responses to perturbations. There are anywhere from one to five Pgb genes in plants that are expressed in response to growth and development and to stress. One of their main functions is to scavenge NO. This review will discuss how Pgb modulates cellular responses to auxin, cytokinin, and jasmonic acid during growth and development and in response to stress. The moderation in the production of reactive oxygen species (ROS) by Pgbs and the effects on PCD will also be discussed. An overall mechanism for Pgb involvement will be presented. PMID- 27371713 TI - One train may hide another: look beyond the aortic valve for cardiac amyloidosis. PMID- 27371714 TI - Prevention of sudden death in hypertrophic cardiomyopathy: bridging the gaps in knowledge. AB - Sudden cardiac death (SCD) is the most devastating complication of hypertrophic cardiomyopathy (HCM). Although the annual rate of SCD in the general HCM population is <1% per year according to contemporary series, there is still a small subset of patients who are at increased risk of SCD. The greatest challenge in the management of HCM is identifying those at increased risk as an implantable cardioverter defibrillator is a potentially life-saving therapy. In this review, we sought to summarize the available data on SCD in HCM and provide a clinical perspective on the current differing and somewhat conflicting European and American recommendations on risk stratification, with balanced guidance with regards to rational clinical decision making. Additionally, we sought to learn more on the actual implementation of the guidelines by HCM experts worldwide. PMID- 27371715 TI - Zooming in on microRNAs for refining cardiovascular risk prediction in secondary prevention. PMID- 27371716 TI - Eminence, common sense, and evidence: a comment to the Andreas Gruntzig lecture 2015. PMID- 27371717 TI - Two hearts, one soul: heterotopic heart transplantation follow-up with cardiac computed tomography. PMID- 27371718 TI - Echo-navigation to guide transfemoral tricuspid edge-to-edge repair. PMID- 27371719 TI - An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the growth rate of small abdominal aortic aneurysms: a randomized placebo-controlled trial (AARDVARK). AB - AIMS: The AARDVARK (Aortic Aneurysmal Regression of Dilation: Value of ACE Inhibition on RisK) trial investigated whether ACE-inhibition reduces small abdominal aortic aneurysms (AAA) growth rate, independent of blood pressure (BP) lowering. METHODS AND RESULTS: A three-arm, multi-centre, single-blind, and randomized controlled trial (ISRCTN51383267) was conducted in 14 hospitals in England. Subjects aged >=55 years with AAA diameter 3.0-5.4 cm were randomized 1:1:1 to receive perindopril arginine 10 mg, or amlodipine 5 mg, or placebo and followed 3-6 monthly over 2 years. The primary outcome was aneurysm growth rate (based on external antero-posterior ultrasound measurements in the longitudinal plane), determined by multi-level modelling to provide maximum likelihood estimates. Two hundred and twenty-four subjects were randomized (2011-2013) to placebo (n = 79), perindopril (n = 73), or amlodipine (n = 72). Mean (SD) changes in mid-trial systolic BP (12 months) were 0.5 (14.3) mmHg, P = 0.78 compared with baseline, -9.5 (13.1) mmHg (P < 0.001), and -6.7 (12.0) mmHg (P < 0.001), respectively. No significant differences in the modelled annual growth rates were apparent [1.68 mm (SE 0.2), 1.77 mm (0.2), and 1.81 mm (0.2), respectively]. The estimated difference in annual growth between the perindopril and placebo groups was 0.08 mm (CI -0.50, 0.65). Similar numbers of AAAs in each group reached 5.5 cm diameter and/or underwent elective surgery: 11 receiving placebo, 10 perindopril, and 11 amlodipine. CONCLUSION: Small AAA growth rates were lower than anticipated, but there was no significant impact of perindopril compared with placebo or placebo and amlodipine, combined despite more effective BP lowering. PMID- 27371720 TI - Avoiding non-responders to cardiac resynchronization therapy: a practical guide. AB - Over two decades after the introduction of cardiac resynchronization therapy (CRT) into clinical practice, ~30% of candidates continue to fail to respond to this highly effective treatment of drug-refractory heart failure (HF). Since the causes of this non-response (NR) are multifactorial, it will require multidisciplinary efforts to overcome. Progress has, thus far, been slowed by several factors, ranging from a lack of consensus regarding the definition of NR and technological limitations to the delivery of therapy. We critically review the various endpoints that have been used in landmark clinical trials of CRT, and the variability in response rates that has been observed as a result of these different investigational designs, different sample populations enrolled and different means of therapy delivered, including new means of multisite and left ventricular endocardial simulation. Precise recommendations are offered regarding the optimal device programming, use of telemonitoring and optimization of management of HF. Potentially reversible causes of NR to CRT are reviewed, with emphasis on loss of biventricular stimulation due to competing arrhythmias. The prevention of NR to CRT is essential to improve the overall performance of this treatment and lower its risk-benefit ratio. These objectives require collaborative efforts by the HF team, the electrophysiologists and the cardiac imaging experts. PMID- 27371721 TI - Beyond EMT: Epithelial STAT3 as a Central Regulator of Fibrogenesis. PMID- 27371722 TI - Natural history and the dawning of a new era for familial ALS. PMID- 27371723 TI - 4DGenome: a comprehensive database of chromatin interactions. PMID- 27371724 TI - The Membrane Phospholipid Binding Protein Annexin A2 Promotes Phagocytosis and Nonlytic Exocytosis of Cryptococcus neoformans and Impacts Survival in Fungal Infection. AB - Cryptococcus neoformans is a fungal pathogen with a unique intracellular pathogenic strategy that includes nonlytic exocytosis, a phenomenon whereby fungal cells are expunged from macrophages without lysing the host cell. The exact mechanism and specific proteins involved in this process have yet to be completely defined. Using murine macrophages deficient in the membrane phospholipid binding protein, annexin A2 (ANXA2), we observed a significant decrease in both phagocytosis of yeast cells and the frequency of nonlytic exocytosis. Cryptococcal cells isolated from Anxa2-deficient (Anxa2(-/-)) bone marrow-derived macrophages and lung parenchyma displayed significantly larger capsules than those isolated from wild-type macrophages and tissues. Concomitantly, we observed significant differences in the amount of reactive oxygen species produced between Anxa2(-/-) and Anxa2(+/+) macrophages. Despite comparable fungal burden, Anxa2(-/-) mice died more rapidly than wild-type mice when infected with C. neoformans, and Anxa2(-/-) mice exhibited enhanced inflammatory responses, suggesting that the reduced survival reflected greater immune-mediated damage. Together, these findings suggest a role for ANXA2 in the control of cryptococcal infection, macrophage function, and fungal morphology. PMID- 27371725 TI - ERAAP Shapes the Peptidome Associated with Classical and Nonclassical MHC Class I Molecules. AB - The peptide repertoire presented by classical as well as nonclassical MHC class I (MHC I) molecules is altered in the absence of the endoplasmic reticulum aminopeptidase associated with Ag processing (ERAAP). To characterize the extent of these changes, peptides from cells lacking ERAAP were eluted from the cell surface and analyzed by high-throughput mass spectrometry. We found that most peptides found in wild-type (WT) cells were retained in the absence of ERAAP. In contrast, a subset of "ERAAP-edited" peptides was lost in WT cells, and ERAAP deficient cells presented a unique "unedited" repertoire. A substantial fraction of MHC-associated peptides from ERAAP-deficient cells contained N-terminal extensions and had a different molecular composition than did those from WT cells. We found that the number and immunogenicity of peptides associated with nonclassical MHC I was increased in the absence of ERAAP. Conversely, only peptides presented by classical MHC I were immunogenic in ERAAP-sufficient cells. Finally, MHC I peptides were also derived from different intracellular sources in ERAAP-deficient cells. PMID- 27371726 TI - Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model. AB - Mechanisms of self-tolerance often result in CD8(+) tumor-infiltrating lymphocytes (TIL) with a hypofunctional phenotype incapable of tumor clearance. Using a transplantable colon carcinoma model, we found that CD8(+) T cells became tolerized in <24 h in an established tumor environment. To define the collective impact of pathways suppressing TIL function, we compared genome-wide mRNA expression of tumor-specific CD8(+) T cells from the tumor and periphery. Notably, gene expression induced during TIL hypofunction more closely resembled self-tolerance than viral exhaustion. Differential gene expression was refined to identify a core set of genes that defined hypofunctional TIL; these data comprise the first molecular profile of tumor-specific TIL that are naturally responding and represent a polyclonal repertoire. The molecular profile of TIL was further dissected to determine the extent of overlap and distinction between pathways that collectively restrict T cell functions. As suggested by the molecular profile of TIL, protein expression of inhibitory receptor LAG-3 was differentially regulated throughout prolonged late-G1/early-S phase of the cell cycle. Our data may accelerate efficient identification of combination therapies to boost anti-tumor function of TIL specifically against tumor cells. PMID- 27371727 TI - Quantification of Human Kallikrein-Related Peptidases in Biological Fluids by Multiplatform Targeted Mass Spectrometry Assays. AB - Human kallikrein-related peptidases (KLKs) are a group of 15 secreted serine proteases encoded by the largest contiguous cluster of protease genes in the human genome. KLKs are involved in coordination of numerous physiological functions including regulation of blood pressure, neuronal plasticity, skin desquamation, and semen liquefaction, and thus represent promising diagnostic and therapeutic targets. Until now, quantification of KLKs in biological and clinical samples was accomplished by enzyme-linked immunosorbent assays (ELISA). Here, we developed multiplex targeted mass spectrometry assays for the simultaneous quantification of all 15 KLKs. Proteotypic peptides for each KLK were carefully selected based on experimental data and multiplexed in single assays. Performance of assays was evaluated using three different mass spectrometry platforms including triple quadrupole, quadrupole-ion trap, and quadrupole-orbitrap instruments. Heavy isotope-labeled synthetic peptides with a quantifying tag were used for absolute quantification of KLKs in sweat, cervico-vaginal fluid, seminal plasma, and blood serum, with limits of detection ranging from 5 to 500 ng/ml. Analytical performance of assays was evaluated by measuring endogenous KLKs in relevant biological fluids, and results were compared with selected ELISAs. The multiplex targeted proteomic assays were demonstrated to be accurate, reproducible, sensitive, and specific alternatives to antibody-based assays. Finally, KLK4, a highly prostate-specific protein and a speculated biomarker of prostate cancer, was unambiguously detected and quantified by immunoenrichment SRM assay in seminal plasma and blood serum samples from individuals with confirmed prostate cancer and negative biopsy. Mass spectrometry revealed exclusively the presence of a secreted isoform and thus unequivocally resolved earlier disputes about KLK4 identity in seminal plasma. Measurements of KLK4 in either 41 seminal plasma or 58 blood serum samples revealed no statistically significant differences between patients with confirmed prostate cancer and negative biopsy. The presented multiplex targeted proteomic assays are an alternative analytical tool to study the biological and pathological roles of human KLKs. PMID- 27371728 TI - Proteomic Analysis of the Plasmodium berghei Gametocyte Egressome and Vesicular bioID of Osmiophilic Body Proteins Identifies Merozoite TRAP-like Protein (MTRAP) as an Essential Factor for Parasite Transmission. AB - Malaria transmission from an infected host to the mosquito vector requires the uptake of intraerythrocytic sexual precursor cells into the mosquito midgut. For the release of mature extracellular gametes two membrane barriers-the parasite parasitophorous vacuole membrane and the host red blood cell membrane-need to be dissolved. Membrane lysis occurs after the release of proteins from specialized secretory vesicles including osmiophilic bodies. In this study we conducted proteomic analyses of the P. berghei gametocyte egressome and developed a vesicular bioID approach to identify hitherto unknown proteins with a potential function in gametocyte egress. This first Plasmodium gametocyte egressome includes the proteins released by the parasite during the lysis of the parasitophorous vacuole membrane and red blood cell membrane. BioID of the osmiophilic body protein MDV1/PEG3 revealed a vesicular proteome of these gametocyte-specific secretory vesicles. Fluorescent protein tagging and gene deletion approaches were employed to validate and identify a set of novel factors essential for this lysis and egress process. Our study provides the first in vivo bioID for a rodent malaria parasite and together with the first Plasmodium gametocyte egressome identifies MTRAP as a novel factor essential for mosquito transmission. Our data provide an important resource for proteins potentially involved in a key step of gametogenesis. PMID- 27371730 TI - Long Noncoding RNA MALAT1 Promotes Aggressive Pancreatic Cancer Proliferation and Metastasis via the Stimulation of Autophagy. AB - Recently, pancreatic ductal adenocarcinoma (PDAC) has emerged as one of the most aggressive malignant tumors with the worst prognosis. Previous studies have demonstrated that long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is increased in pancreatic cancer and is identified as a diagnostic biomarker. Nonetheless, the molecular mechanism of elevated MALAT1 levels and tumor aggressiveness remains unknown. In this study, MALAT1 was found to be highly expressed in PDAC tissues, and elevated expression was associated with poorer prognoses. In addition, MALAT1 was positively linearly correlated with the expression of LC3B mRNA. Furthermore, several molecules involved in cellular autophagic flux were modulated following the downregulation of MALAT1, including LC3, P62, and LAMP-2. Mechanistically, we found that MALAT1 interacted with RNA binding protein HuR, and silencing of MALAT1 greatly enhanced the posttranscriptional regulation of TIA-1 and had further effects on inhibiting autophagy. MALAT1 was speculated to regulate tumorigenesis via HuR-TIA-1-mediated autophagic activation. Hence, we investigated the biological properties of MALAT1 in terms of tumor proliferation and metastasis by promoting autophagy in vitro In brief, these data demonstrate that MALAT1 could facilitate the advanced progression of tumors in vivo Our study highlights the new roles of MALAT1 on protumorigenic functioning and anticancer therapy via activating autophagy in pancreatic cancer. Mol Cancer Ther; 15(9); 2232-43. (c)2016 AACR. PMID- 27371729 TI - Covalent Targeting of Fibroblast Growth Factor Receptor Inhibits Metastatic Breast Cancer. AB - Therapeutic targeting of late-stage breast cancer is limited by an inadequate understanding of how tumor cell signaling evolves during metastatic progression and by the currently available small molecule inhibitors capable of targeting these processes. Herein, we demonstrate that both beta3 integrin and fibroblast growth factor receptor-1 (FGFR1) are part of an epithelial-mesenchymal transition (EMT) program that is required to facilitate metastatic outgrowth in response to fibroblast growth factor-2 (FGF2). Mechanistically, beta3 integrin physically disrupts an interaction between FGFR1 and E-cadherin, leading to a dramatic redistribution of FGFR1 subcellular localization, enhanced FGF2 signaling and increased three-dimensional (3D) outgrowth of metastatic breast cancer cells. This ability of beta3 integrin to drive FGFR signaling requires the enzymatic activity of focal adhesion kinase (FAK). Consistent with these mechanistic data, we demonstrate that FGFR, beta3 integrin, and FAK constitute a molecular signature capable of predicting decreased survival of patients with the basal like subtype of breast cancer. Importantly, covalent targeting of a conserved cysteine in the P-loop of FGFR1-4 with our newly developed small molecule, FIIN 4, more effectively blocks 3D metastatic outgrowth as compared with currently available FGFR inhibitors. In vivo application of FIIN-4 potently inhibited the growth of metastatic, patient-derived breast cancer xenografts and murine-derived metastases growing within the pulmonary microenvironment. Overall, the current studies demonstrate that FGFR1 works in concert with other EMT effector molecules to drive aberrant downstream signaling, and that these events can be effectively targeted using our novel therapeutics for the treatment of the most aggressive forms of breast cancer. Mol Cancer Ther; 15(9); 2096-106. (c)2016 AACR. PMID- 27371731 TI - Macrophage micro-RNA-155 promotes lipopolysaccharide-induced acute lung injury in mice and rats. AB - Micro-RNA (miR)-155 is a novel gene regulator with important roles in inflammation. Herein, our study aimed to explore the role of miR-155 in LPS induced acute lung injury(ALI). ALI in mice was induced by intratracheally delivered LPS. Loss-of-function experiments performed on miR-155 knockout mice showed that miR-155 gene inactivation protected mice from LPS-induced ALI, as manifested by preserved lung permeability and reduced lung inflammation compared with wild-type controls. Bone marrow transplantation experiments identified leukocytes, but not lung parenchymal-derived miR-155-promoted acute lung inflammation. Real-time PCR analysis showed that the expression of miR-155 in lung tissue was greatly elevated in wild-type mice after LPS stimulation. In situ hybridization showed that miR-155 was mainly expressed in alveolar macrophages. In vitro experiments performed in isolated alveolar macrophages and polarized bone marrow-derived macrophages confirmed that miR-155 expression in macrophages was increased in response to LPS stimulation. Conversely, miR-155 gain-of function in alveolar macrophages remarkably exaggerated LPS-induced acute lung injury. Molecular studies identified the inflammation repressor suppressor of cytokine signaling (SOCS-1) as the downstream target of miR-155. By binding to the 3'-UTR of the SOCS-1 mRNA, miR-155 downregulated SOCS-1 expression, thus, permitting the inflammatory response during lung injury. Finally, we generated a novel miR-155 knockout rat strain and showed that the proinflammatory role of miR 155 was conserved in rats. Our study identified miR-155 as a proinflammatory factor after LPS stimulation, and alveolar macrophages-derived miR-155 has an important role in LPS-induced ALI. PMID- 27371732 TI - Phospholipase C-epsilon signaling mediates endothelial cell inflammation and barrier disruption in acute lung injury. AB - Phospholipase C-epsilon (PLC-epsilon) is a unique PLC isoform that can be regulated by multiple signaling inputs from both Ras family GTPases and heterotrimeric G proteins and has primary sites of expression in the heart and lung. Whereas the role of PLC-epsilon in cardiac function and pathology has been documented, its relevance in acute lung injury (ALI) is unclear. We used PLC epsilon(-/-) mice to address the role of PLC-epsilon in regulating lung vascular inflammation and injury in an aerosolized bacterial LPS inhalation mouse model of ALI. PLC-epsilon(-/-) mice showed a marked decrease in LPS-induced proinflammatory mediators (ICAM-1, VCAM-1, TNF-alpha, IL-1beta, IL-6, macrophage inflammatory protein 2, keratinocyte-derived cytokine, monocyte chemoattractant protein 1, and granulocyte-macrophage colony-stimulating factor), lung neutrophil infiltration and microvascular leakage, and loss of VE-cadherin compared with PLC epsilon(+/+) mice. These data identify PLC-epsilon as a critical determinant of proinflammatory and leaky phenotype of the lung. To test the possibility that PLC epsilon activity in endothelial cells (EC) could contribute to ALI, we determined its role in EC inflammation and barrier disruption. RNAi knockdown of PLC-epsilon inhibited NF-kappaB activity in response to diverse proinflammatory stimuli, thrombin, LPS, TNF-alpha, and the nonreceptor agonist phorbol 13-myristate 12 acetate (phorbol esters) in EC. Depletion of PLC-epsilon also inhibited thrombin induced expression of NF-kappaB target gene, VCAM-1. Importantly, PLC-epsilon knockdown also protected against thrombin-induced EC barrier disruption by inhibiting the loss of VE-cadherin at adherens junctions and formation of actin stress fibers. These data identify PLC-epsilon as a novel regulator of EC inflammation and permeability and show a hitherto unknown role of PLC-epsilon in the pathogenesis of ALI. PMID- 27371733 TI - Glucocorticoid and TNF signaling converge at A20 (TNFAIP3) to repress airway smooth muscle cytokine expression. AB - Airway smooth muscle is a major target tissue for glucocorticoid (GC)-based asthma therapies, however, molecular mechanisms through which the GC receptor (GR) exerts therapeutic effects in this key airway cell type have not been fully elucidated. We previously identified the nuclear factor-kappaB (NF-kappaB) inhibitor, A20 (TNFAIP3), as a mediator of cytokine repression by glucocorticoids (GCs) in airway epithelial cells and defined cooperative regulation of anti inflammatory genes by GR and NF-kappaB as a key mechanistic underpinning of airway epithelial GR function. Here, we expand on these findings to determine whether a similar mechanism is operational in human airway smooth muscle (HASM). Using HASM cells derived from normal and fatal asthma samples as an in vitro model, we demonstrate that GCs spare or augment TNF-mediated induction of A20 (TNFAIP3), TNIP1, and NFKBIA, all implicated in negative feedback control of NF kappaB-driven inflammatory processes. We applied chromatin immunoprecipitation and reporter analysis to show that GR and NF-kappaB directly regulate A20 expression in HASM through cooperative induction of an intronic enhancer. Using overexpression, we show for the first time that A20 and its interacting partner, TNIP1, repress TNF signaling in HASM cells. Moreover, we applied small interfering RNA-based gene knockdown to demonstrate that A20 is required for maximal cytokine repression by GCs in HASM. Taken together, our data suggest that inductive regulation of A20 by GR and NF-kappaB contributes to cytokine repression in HASM. PMID- 27371734 TI - Boysenberry ingestion supports fibrolytic macrophages with the capacity to ameliorate chronic lung remodeling. AB - Lung fibrosis negatively impacts on lung function in chronic asthma and is linked to the development of profibrotic macrophage phenotypes. Epidemiological studies have found that lung function benefits from increased consumption of fruit high in polyphenols. We investigated the effect of boysenberry consumption, in both therapeutic and prophylactic treatment strategies in a mouse model of chronic antigen-induced airway inflammation. Boysenberry consumption reduced collagen deposition and ameliorated tissue remodeling alongside an increase in the presence of CD68+CD206+arginase+ alternatively activated macrophages in the lung tissue. The decrease in tissue remodeling was associated with increased expression of profibrolytic matrix metalloproteinase-9 protein in total lung tissue. We identified alternatively activated macrophages in the mice that consumed boysenberry as a source of the matrix metalloproteinase-9. Oral boysenberry treatment may moderate chronic tissue remodeling by supporting the development of profibrolytic alternatively activated macrophages expressing matrix metalloproteinase-9. Regular boysenberry consumption therefore has the potential to moderate chronic lung remodeling and fibrosis in asthma and other chronic pulmonary diseases. PMID- 27371735 TI - Tumor necrosis factor regulates NMDA receptor-mediated airway smooth muscle contractile function and airway responsiveness. AB - We have shown that N-methyl-d-aspartate receptors (NMDA-Rs) are receptor-operated calcium entry channels in human airway smooth muscle (HASM) during contraction. Tumor necrosis factor (TNF) augments smooth muscle contractility by influencing pathways that regulate intracellular calcium flux and can alter NMDA-R expression and activity in cortical neurons and glial cells. We hypothesized that NMDA-R mediated Ca(2+) and contractile responses of ASM can be altered by inflammatory mediators, including TNF. In cultured HASM cells, we assessed TNF (10 ng/ml, 48 h) effect on NMDA-R subunit abundance by quantitative PCR, confocal imaging, and immunoblotting. We observed dose- and time-dependent changes in NMDA-R composition: increased obligatory NR1 subunit expression and altered regulatory NR2 and inhibitory NR3 subunits. Measuring intracellular Ca(2+) flux in Fura-2 loaded HASM cultures, we observed that TNF exposure enhanced cytosolic Ca(2+) mobilization and changed the temporal pattern of Ca(2+) flux in individual myocytes induced by NMDA, an NMDA-R selective analog of glutamate. We measured airway responses to NMDA in murine thin-cut lung slices (TCLS) from allergen naive animals and observed significant airway contraction. However, NMDA acted as a bronchodilator in TCLS from house dust mice-challenged mice and in allergen naive TCLS subjected to TNF exposure. All contractile or bronchodilator responses were blocked by a selective NMDA-R antagonist, (2R)-amino-5-phosphonopentanoate, and bronchodilator responses were prevented by N(G)-nitro-l-arginine methyl ester (nitric oxide synthase inhibitor) or indomethacin (cyclooxygenase inhibitor). Collectively, we show that TNF augments NMDA-R-mediated Ca(2+) mobilization in HASM cells, whereas in multicellular TCLSs allergic inflammation and TNF exposure leads to NMDA-R-mediated bronchodilation. These findings reveal the unique contribution of ionotrophic NMDA-R to airway hyperreactivity. PMID- 27371737 TI - ErbB2: From an EGFR Relative to a Central Target for Cancer Therapy. PMID- 27371738 TI - Commentary on "Participation of p53 Protein in the Cellular Response to DNA Damage". PMID- 27371740 TI - Abstract statistics. PMID- 27371742 TI - Aims and Scope. PMID- 27371739 TI - Systemic DC Activation Modulates the Tumor Microenvironment and Shapes the Long Lived Tumor-Specific Memory Mediated by CD8+ T Cells. AB - Strategies to reprogram the tumor microenvironment are being explored to improve cancer immunotherapy. In one approach, we have targeted dendritic cells (DC) to improve their function with adjuvant vector cells (aAVC) that are engineered from NKT ligand-loaded CD1d(+) allogeneic cells transfected with tumor antigen mRNAs. Here, we report the finding that this approach also programs local immune responses by establishing tertiary lymphoid structures (TLS), which include expanded antigen-specific CD8(+) T-cell clones, mobilized DCs, and normalized tumor vasculature. aAVC therapy also expanded specific Vbeta-expressing antitumor T-cell clones, leading to the formation of long-term memory T cells. When combined with PD-1 blockade, aAVC infusion triggered regression of poorly immunogenic tumor cells that did not respond to PD-1 blockade alone, as well as expansion of antigen-specific CD8(+) T-cell clones in the tumor. The findings of this study help to inform a next-generation platform for the generation of efficacious cancer vaccines. Cancer Res; 76(13); 3756-66. (c)2016 AACR. PMID- 27371745 TI - Pathways for salvage and protection of the heart under stress: novel routes for cardiac rejuvenation. AB - The world population is aging, and by 2017, there will be more people over the age of 65 than under age 5, and by 2050, two billion of the estimated nine billion people on Earth will be older than 60. Aging itself is a major cardiovascular risk factor, affecting morbidity and mortality of the aging population. At the same time, aging increases the likelihood of the presence of other risk factors. The aged myocardium is characterized by several structural and functional progressive changes that impair its ability to respond appropriately to stressful conditions. Although some progress to understand the complex mechanisms that underlie these phenotypic changes, the molecular pathways that determine the balance between aging and rejuvenation in the aged myocardium still remain elusive. In this article, we review molecular mechanisms responsible for the phenotypic changes observed with aging in the heart, providing insight into molecular pathways and pharmacological interventions that may rejuvenate the aged myocardium. A better understanding of these pathways is essential for determining their therapeutic potential in humans, improving the possibility that the increase in life expectancy that we are observing will be accompanied by a parallel increase in healthspan. PMID- 27371746 TI - Biventricular metastatic invasion from cervical squamous cell carcinoma. AB - Metastasis to the heart has been previously described with primary lung and breast carcinoma, lymphoma, leukaemia, mesothelioma and melanoma. However, left ventricular cardiac metastasis from primary cervical squamous cell carcinoma is poorly described. This report describes the clinical presentation of a patient with cardiac metastatic invasion from cervical cancer. PMID- 27371757 TI - Retraction: Confounding of the Association between Radiation Exposure from CT Scans and Risk of Leukemia and Brain Tumors by Cancer Susceptibility Syndromes. PMID- 27371756 TI - Anticipating the "Silver Tsunami": Prevalence Trajectories and Comorbidity Burden among Older Cancer Survivors in the United States. AB - BACKGROUND: Cancer survivors are a growing population, due in large part to the aging of the baby boomer generation and the related "silver tsunami" facing the U.S. health care system. Understanding the impact of a graying nation on cancer prevalence and comorbidity burden is critical in informing efforts to design and implement quality cancer care for this population. METHODS: Incidence and survival data from 1975 to 2011 were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program to estimate current cancer prevalence. SEER-Medicare claims data were used to estimate comorbidity burden. Prevalence projections were made using U.S. Census Bureau data and the Prevalence Incidence Approach Model, assuming constant future incidence and survival trends but dynamic projections of the U.S. RESULTS: In 2016, there were an estimated 15.5 million cancer survivors living in the United States, 62% of whom were 65 years or older. The prevalent population is projected to grow to 26.1 million by 2040, and include 73% of survivors who are 65 years and older. Comorbidity burden was highest in the oldest survivors (those >=85 years) and worst among lung cancer survivors. CONCLUSIONS: Older adults, who often present with complex health needs, now constitute the majority of cancer survivors and will continue to dominate the survivor population over the next 24 years. IMPACT: The oldest adults (i.e., those >75 years) should be priority populations in a pressing cancer control and prevention research agenda that includes expanding criteria for clinical trials to recruit more elderly participants and developing relevant supportive care interventions. Cancer Epidemiol Biomarkers Prev; 25(7); 1029-36. (c)2016 AACR. PMID- 27371758 TI - Biphasic Positive Airway Pressure or Continuous Positive Airway Pressure: A Randomized Trial. AB - BACKGROUND: There is currently no clear evidence that nasal-biphasic positive airway pressure (n-BiPAP) confers any advantage over nasal-continuous positive airway pressure (n-CPAP). Our hypothesis was that preterm infants born before 30 weeks' gestation and <2 weeks old when extubated onto n-BiPAP will have a lower risk of extubation failure than infants extubated onto n-CPAP at equivalent mean airway pressure. METHODS: We conducted an unblinded multicenter randomized trial comparing n-CPAP with n-BiPAP in infants born <30 weeks' gestation and <2 weeks old. The primary outcome variable was the rate of extubation failure within 48 hours after the first attempt at extubation. Block randomization stratified by center and gestation (<28 weeks or >=28 weeks) was performed. RESULTS: A total of 540 infants (270 in each group) were eligible to be included in the statistical analysis; 57 (21%) of n-BiPAP group and 55 (20%) of n-CPAP group failed extubation at 48 hours postextubation (adjusted odds ratio 1.01; 95% confidence interval 0.65-1.56; P = .97). Subgroup analysis of infants born before and after 28 weeks' gestation showed no significant differences between the 2 groups. There were no significant differences between arms in death; oxygen requirement at 28 days; oxygen requirement at 36 weeks' corrected gestation; or intraventricular hemorrhage, necrotizing enterocolitis requiring surgery, or pneumothorax. CONCLUSIONS: This trial shows that there is no added benefit to using n-BIPAP over n-CPAP at equivalent mean airway pressure in preventing extubation failures in infants born before 30 weeks' gestation and <2 weeks old. PMID- 27371759 TI - Adolescents, Family History, and Inherited Disease Risk: An Opportunity. PMID- 27371760 TI - Asymptomatic Kawasaki Disease in a 3-Month-Old Infant. AB - Kawasaki disease (KD) is the leading cause of acquired heart disease in children in the United States. It is a systemic vasculitis characterized by diffuse inflammation of medium and small blood vessels. If untreated it can lead to myocardial infarction, ischemic heart disease, or sudden death. Early recognition and treatment decrease the incidence of coronary consequences, resulting in improved clinical outcomes. Incomplete KD is much less likely to fulfill major clinical diagnostic criteria. Infants <12 months of age are more likely to have an incomplete presentation, and children <6 months of age are more likely to develop cardiac complications. We present a case of a 3-month-old, previously healthy white boy who was noted to have a new transient cardiac murmur during a routine health assessment. He was completely asymptomatic, and physical examination was otherwise within normal limits. An echocardiogram was performed and showed abnormal dilation of several coronary arteries, consistent with the coronary ectasia associated with KD. Laboratory evaluation was significant for values suggestive of systemic inflammation. Based on these results, a presumed diagnosis of incomplete KD was made and treatment administered. Close surveillance was undertaken, and serial laboratory studies and imaging showed gradual resolution of inflammatory markers and cardiac ectasia. This unique case of incomplete KD without any of the physical signs normally associated with the disease emphasizes the spectrum of presentation and the possibility of missing a diagnosis of incomplete disease, reinforcing the need to remain vigilant. PMID- 27371761 TI - Functional specialization of areas along the anterior-posterior axis of the primate prefrontal cortex. AB - Functional specialization of areas along the anterior-posterior axis of the lateral prefrontal cortex has been speculated but little evidence exists about distinct neurophysiological properties between prefrontal sub-regions. To address this issue we divided the lateral prefrontal cortex into a posterior-dorsal, a mid-dorsal, an anterior-dorsal, a posterior-ventral, and an anterior ventral region. Selectivity for spatial locations, shapes, and colors was evaluated in six monkeys never trained in working memory tasks, while they viewed the stimuli passively. Recordings from over two thousand neurons revealed systematic differences between anterior and posterior regions. In the dorsal prefrontal cortex, anterior regions exhibited the largest receptive fields, longest response latencies, and lowest amount of information for stimuli. In the ventral prefrontal cortex, posterior regions were characterized by a low percentage of responsive neurons to any stimuli we used, consistent with high specialization for stimulus features. Additionally, spatial information was more prominent in the dorsal and color in ventral regions. Our results provide neurophysiological evidence for a rostral-caudal gradient of stimulus selectivity through the prefrontal cortex, suggesting that posterior areas are selective for stimuli even when these are not releant for execution of a task, and that anterior areas are likely engaged in more abstract operations. PMID- 27371762 TI - Volume Loss of the Nucleus Basalis of Meynert is Associated with Atrophy of Innervated Regions in Mild Cognitive Impairment. AB - Extensive research suggests that basal forebrain (BF) cholinergic neurons are selectively vulnerable to Alzheimer's disease (AD). However, it remains unknown whether volume loss of BF cholinergic compartments parallels structural changes of their innervated regions in prodromal AD. To this aim, we have correlated volume of each BF compartment with cortical thickness and hippocampus/amygdala volume in 106 healthy older (HO) adults and 106 amnestic mild cognitive impairment (aMCI) patients. Correlations were limited to regions affected by atrophy in aMCI. The volume of the nucleus basalis of Meynert (NBM/Ch4) was positively correlated with thickness of the temporal cortex in aMCI, and with volume of amygdala in HO and aMCI, separately. Volume of the medial septum/diagonal band of Broca (Ch1-Ch3) was also positively correlated with volume of the hippocampus within the 2 groups. Only correlations between the NBM and their innervated regions showed diagnostic value. Unlike men, aMCI women showed a stronger association between volume of the NBM and thickness of the temporal lobe when compared with HO women. Altogether, these results reveal, for the first time in humans, that atrophy of NBM is associated with structural changes of their innervated regions in prodromal AD, being this relationship more evident in women. PMID- 27371763 TI - Developmental Alcohol Exposure Impairs Activity-Dependent S-Nitrosylation of NDEL1 for Neuronal Maturation. AB - Neuronal nitric oxide synthase is involved in diverse signaling cascades that regulate neuronal development and functions via S-Nitrosylation-mediated mechanism or the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway activated by nitric oxide. Although it has been studied extensively in vitro and in invertebrate animals, effects on mammalian brain development and underlying mechanisms remain poorly understood. Here we report that genetic deletion of "Nos1" disrupts dendritic development, whereas pharmacological inhibition of the sGC/cGMP pathway does not alter dendritic growth during cerebral cortex development. Instead, nuclear distribution element like (NDEL1), a protein that regulates dendritic development, is specifically S nitrosylated at cysteine 203, thereby accelerating dendritic arborization. This post-translational modification is enhanced by N-methyl-D-aspartate receptor mediated neuronal activity, the main regulator of dendritic formation. Notably, we found that disruption of S-Nitrosylation of NDEL1 mediates impaired dendritic maturation caused by developmental alcohol exposure, a model of developmental brain abnormalities resulting from maternal alcohol use. These results highlight S-Nitrosylation as a key activity-dependent mechanism underlying neonatal brain maturation and suggest that reduction of S-Nitrosylation of NDEL1 acts as a pathological factor mediating neurodevelopmental abnormalities caused by maternal alcohol exposure. PMID- 27371765 TI - The absence of attenuating effect of red light exposure on pre-existing melanopsin-driven post-illumination pupil response. AB - It has been proposed that after activation by blue light, activated melanopsin is converted back to its resting state by long wavelength red light exposure, a putative mechanism of melanopsin chromophore recovery in vivo. We tested this hypothesis by investigating whether red light attenuates the ongoing post illumination pupil response (PIPR) induced by melanopsin-activating blue light. Pupillary light responses were tested using "Blue+Red" double flashes and "Blue Only" single flash stimuli in 10 visually normal subjects. For "Blue+Red" conditions, PIPR was induced with an intense blue flash, followed by experimental red light exposure of variable intensity and duration (Experiment 1) immediately or 9s after the offset of the blue flash (Experiment 2). For "Blue Only" conditions, only the PIPR-inducing blue stimuli were presented (reference condition). PIPR was defined as the mean pupil size from 10 to 30s (Experiment 1) and from 25 to 60s (Experiment 2) after the offset of blue light stimuli. The results showed that PIPR from "Blue+Red" conditions did not differ significantly from those of "Blue Only" conditions (p=0.55) in Experiment 1. The two stimulation conditions also did not differ in Experiment 2 (p=0.38). We therefore conclude that red light exposure does not alter the time course of PIPR induced by blue light. This finding does not support the hypothesis that long wavelength red light reverses activated melanopsin; rather it lends support to the hypothesis that the wavelengths of stimuli driving both the forward and backward reactions of melanopsin may be similar. PMID- 27371766 TI - Selective orienting to pleasant versus unpleasant visual scenes. AB - We investigated the relative attentional capture by positive versus simultaneously presented negative images in extrafoveal vision for female observers. Pairs of task-irrelevant pleasant and unpleasant visual scenes were displayed peripherally (?5 degrees away from fixation) during a task-relevant letter-discrimination task at fixation. Selective attentional orienting was assessed by the probability of first fixating each scene and the time until first fixation. Results revealed a higher first fixation probability and shorter entry times, followed by longer dwell times, for pleasant relative to unpleasant scenes. The attentional capture advantage by pleasant scenes occurred in the absence of differences in perceptual properties. Processing of affective scene significance automatically occurs through covert attention in peripheral vision early. At least in non-threatening conditions, the attentional system is tuned to initially orient to pleasant images when competing with unpleasant ones. PMID- 27371764 TI - Individual Differences in the Alignment of Structural and Functional Markers of the V5/MT Complex in Primates. AB - Extrastriate visual area V5/MT in primates is defined both structurally by myeloarchitecture and functionally by distinct responses to visual motion. Myelination is directly identifiable from postmortem histology but also indirectly by image contrast with structural magnetic resonance imaging (sMRI). First, we compared the identification of V5/MT using both sMRI and histology in Rhesus macaques. A section-by-section comparison of histological slices with in vivo and postmortem sMRI for the same block of cortical tissue showed precise correspondence in localizing heavy myelination for V5/MT and neighboring MST. Thus, sMRI in macaques accurately locates histologically defined myelin within areas known to be motion selective. Second, we investigated the functionally homologous human motion complex (hMT+) using high-resolution in vivo imaging. Humans showed considerable intersubject variability in hMT+ location, when defined with myelin-weighted sMRI signals to reveal structure. When comparing sMRI markers to functional MRI in response to moving stimuli, a region of high myelin signal was generally located within the hMT+ complex. However, there were considerable differences in the alignment of structural and functional markers between individuals. Our results suggest that variation in area identification for hMT+ based on structural and functional markers reflects individual differences in human regional brain architecture. PMID- 27371767 TI - Impact of active smoking on survival of patients with metastatic lung adenocarcinoma harboring an epidermal growth factor receptor (EGFR) mutation. AB - Lung cancer in smokers and non-smokers demonstrates distinct genetic profiles, and cigarette smoking affects epidermal growth factor receptor (EGFR) function and causes secondary EGFR tyrosine kinase resistance. We evaluated the effect of active smoking in patients with metastatic lung adenocarcinoma. A total of 132 metastatic lung adenocarcinoma patients, diagnosed between 2008 and 2013, with known EGFR mutation status, were evaluated retrospectively. Among these patients, 40 had an activating EGFR mutation. Patients who continued smoking during the treatment were defined as active smokers. Former smokers and never smokers were together defined as non-smokers. The outcomes of the treatment in relation to the EGFR mutation and smoking status were evaluated. The median follow-up time was 10.5 months. The overall response rate for the first-line therapy was significantly higher among the EGFR-mutant patients (p = 0.01), however, smoking status had no impact on the response rate (p = 0.1). The EGFR-mutant active smokers progressed earlier than the non-smokers (p < 0.01). The overall survival (OS) of the non-smokers and patients treated with erlotinib was significantly longer (p = 0.02 and p = 0.01, respectively). Smoking status did not affect the OS in EGFR wild type tumors (p = 0.49) but EGFR-mutant non-smokers had a longer OS than the active smokers (p = 0.01).The active smokers treated with erlotinib had poorer survival than the non-smokers (p = 0.03). Multivariate analysis of EGFR-mutant patients showed that erlotinib treatment at any line and non-smoking were independent prognostic factors for the OS (p = 0.04 and p = 0.01, respectively). Smoking during treatment is a negative prognostic factor in metastatic lung adenocarcinoma with an EGFR mutation. PMID- 27371768 TI - "Model age-based" and "copy when uncertain" biases in children's social learning of a novel task. AB - Theoretical models of social learning predict that individuals can benefit from using strategies that specify when and whom to copy. Here the interaction of two social learning strategies, model age-based biased copying and copy when uncertain, was investigated. Uncertainty was created via a systematic manipulation of demonstration efficacy (completeness) and efficiency (causal relevance of some actions). The participants, 4- to 6-year-old children (N=140), viewed both an adult model and a child model, each of whom used a different tool on a novel task. They did so in a complete condition, a near-complete condition, a partial demonstration condition, or a no-demonstration condition. Half of the demonstrations in each condition incorporated causally irrelevant actions by the models. Social transmission was assessed by first responses but also through children's continued fidelity, the hallmark of social traditions. Results revealed a bias to copy the child model both on first response and in continued interactions. Demonstration efficacy and efficiency did not affect choice of model at first response but did influence solution exploration across trials, with demonstrations containing causally irrelevant actions decreasing exploration of alternative methods. These results imply that uncertain environments can result in canalized social learning from specific classes of model. PMID- 27371770 TI - The contributions of biomass burning to primary and secondary organics: A case study in Pearl River Delta (PRD), China. AB - Synchronized online measurements of gas- and particle- phase organics including non-methane hydrocarbons (NMHCs), oxygenated volatile organic compounds (OVOCs) and submicron organic matters (OM) were conducted in November 2010 at Heshan, Guangdong provincial supersite, China. Several biomass burning events were identified by using acetonitrile as a tracer, and enhancement ratios (EnRs) of organics to carbon monoxide (CO) obtained from this work generally agree with those from rice straw burning in previous studies. The influences of biomass burning on NMHCs, OVOCs and OM were explored by comparing biomass burning impacted plumes (BB plumes) and non-biomass burning plumes (non-BB plumes). A photochemical age-based parameterization method was used to characterize primary emission and chemical behavior of those three organic groups. The emission ratios (EmRs) of NMHCs, OVOCs and OM to CO increased by 27-71%, 34-55% and 67% in BB plumes, respectively, in comparison with non-BB plumes. The estimated formation rate of secondary organic aerosol (SOA) in BB plumes was found to be 24% faster than non-BB plumes. By applying the above emission ratios to the whole PRD, the annual emissions of VOCs and OM from open burning of crop residues would be 56.4 and 3.8Gg in 2010 in PRD, respectively. PMID- 27371769 TI - Testosterone and depressive symptoms among men in the Diabetes Prevention Program. AB - OBJECTIVE: We examined associations between intensive lifestyle intervention (ILS) and changes in testosterone and associations with mood among middle-aged men. DESIGN: Secondary analysis of men (n=886) participating in the Diabetes Prevention Program which randomized glucose-intolerant, overweight men to ILS, metformin, or placebo between 1996 and 1999. MAIN OUTCOME MEASURES: Changes in testosterone between baseline and 1-year follow-up asnd associations of these changes with mood measures (Beck Depression Inventory [BDI-II], Beck Anxiety Inventory [BAI]). RESULTS: Median baseline testosterone was 10.98nmol/l and 44% (n=385) had testosterone<10.41nmol/l or 300ng/dl. Testosterone increases were greater among men randomized to ILS vs. metformin vs. placebo (1.15nmol/l vs. 0.12nmol/l vs. -0.27nmol/l, p<0.001). The association between changes in testosterone and mood differed by study arm (p<0.001 for interaction); there were no significant associations between changes in testosterone and mood changes among men in the ILS or placebo arms. Among men in the metformin arm, increases in testosterone were significantly associated with decreases in BDI-II (improved depressive symptoms) (beta-coefficient -0.2336, p=0.0002) indicating a 0.23 decrease in BDI-II for every 1nmol/l increase in testosterone and decreases in BAI (improved anxiety symptoms) (beta-coefficient -0.2147, p=0.0014). Similar patterns were observed for bioavailable testosterone. CONCLUSIONS: Among overweight middle-aged men with glucose-intolerance, ILS increased endogenous testosterone slightly but without significant improvements in mood. Metformin did not increase testosterone, but among metformin users, testosterone increases were associated with improvements in mood. Thus, interventions that increase endogenous testosterone may not also improve mood. PMID- 27371771 TI - Heavy metal removal by GLDA washing: Optimization, redistribution, recycling, and changes in soil fertility. AB - Soil washing, an emerging method for treating soils contaminated by heavy metals, requires an evaluation of its efficiency in simultaneously removing different metals, the quality of the soil following remediation, and the reusability of the recycled washing agent. In this study, we employed N,N-bis (carboxymethyl)-l glutamic acid (GLDA), a novel and readily biodegradable chelator to remove Cd, Pb, and Zn from polluted soils. We investigated the influence of washing conditions, including GLDA concentration, pH, and contact time on their removal efficiencies. The single factor experiments showed that Cd, Pb, and Zn removal efficiencies reached 70.62, 74.45, and 34.43% in mine soil at a GLDA concentration of 75mM, a pH of 4.0, and a contact time of 60min, and in polluted farmland soil, removal efficiencies were 69.12, 78.30, and 39.50%, respectively. We then employed response surface methodology to optimize the washing parameters. The optimization process showed that the removal efficiencies were 69.50, 88.09, and 40.45% in mine soil and 71.34, 81.02, and 50.95% in polluted farmland soil for Cd, Pb, and Zn, respectively. Moreover, the overall highly effective removal of Cd and Pb was connected mainly to their highly effective removal from the water-soluble, exchangeable, and carbonate fractions. GLDA-washing eliminated the same amount of metals as EDTA-washing, while simultaneously retaining most of the soil nutrients. Removal efficiencies of recycled GLDA were no >5% lower than those of the fresh GLDA. Therefore, GLDA could potentially be used for the rehabilitation of soil contaminated by heavy metals. PMID- 27371772 TI - Combining natural background levels (NBLs) assessment with indicator kriging analysis to improve groundwater quality data interpretation and management. AB - The natural background level (NBL) concept is revisited and combined with indicator kriging method to analyze the spatial distribution of groundwater quality within a groundwater body (GWB). The aim is to provide a methodology to easily identify areas with the same probability of exceeding a given threshold (which may be a groundwater quality criteria, standards, or recommended limits for selected properties and constituents). Three case studies with different hydrogeological settings and located in two countries (Portugal and Italy) are used to derive NBL using the preselection method and validate the proposed methodology illustrating its main advantages over conventional statistical water quality analysis. Indicator kriging analysis was used to create probability maps of the three potential groundwater contaminants. The results clearly indicate the areas within a groundwater body that are potentially contaminated because the concentrations exceed the drinking water standards or even the local NBL, and cannot be justified by geogenic origin. The combined methodology developed facilitates the management of groundwater quality because it allows for the spatial interpretation of NBL values. PMID- 27371773 TI - Influence of adipocytokines in periprostatic adipose tissue on prostate cancer aggressiveness. AB - OBJECTIVE: To evaluate the correlation between the level of adipocytokines expression in periprostatic adipose tissue and the prostate cancer aggressiveness. PATIENTS AND METHOD: The periprostatic adipose tissues were collected from 30 patients who underwent radical retropubic prostatectomy. The subcutaneous adipose, periprostatic adipose tissues and prostate cancer tissue from the same patient were collected from 10 patients for match research. The expression level of IL-6, Leptin and Adiponectin was detected by immunohistochemistry and by Real-time quantitative PCR in periprostatic adipose tissues. RESULT: There were differences in the positive rates of IL-6, Leptin and Adiponectin expression in the periprostate adipose between prostate cancer and control (P<0.001, P=0.032, 0.003). Nothing but the "IL-6 expression intensity" was seen in difference with the aggressiveness of prostate cancer (P=0.001), and was relevant with the prostate cancer aggressiveness (rs=0.668, P<0.001); The mRNA expression of IL-6 in periprostatic adipose tissues of prostate cancer was higher than that of control (P=0.049), and the mRNA expression of Adiponectin was lower (P<0.0001); IL-6 mRNA expression in periprostate adipose tissue and prostate cancer tissue were higher than that in subcutaneous adipose (P<0.001, P=0.001); IL-6 mRNA expression in periprostate adipose was correlated with that in prostate cancer tissue (r=0.663, p=0.036); Adiponectin mRNA expression in prostate cancer tissue was lower than that in periprostate adipose (P=0.006), and Adiponectin mRNA expression in periprostate adipose was correlated with that in prostate cancer tissue (r=0.707, p=0.022). CONCLUSION: IL-6, Leptin and Adiponectin were expressed in the periprostatic adipose tissues, which constitute the microenvironment of prostate cancer aggressiveness. There might be intimate relationship between periprostate adipose and prostate cancer tissue. PMID- 27371774 TI - Y-box protein-1/p18 as novel serum marker for ovarian cancer diagnosis: A study by the Tumor Bank Ovarian Cancer (TOC). AB - INTRODUCTION: The cold shock Y-box binding protein-1 (YB-1) fulfills important roles in regulating cell proliferation and differentiation. Overexpression occurs in various tumor cells. Given the existence of extracellular YB-1 we set out to determine the diagnostic, predictive and prognostic role of serum YB-1/p18 for patients with primary epithelial ovarian cancer (EOC). METHODS: The protein fragment YB-1/p18 was quantified by sandwich ELISA in serum samples from 132 healthy female volunteers and 206 patients with histological diagnosis of primary EOC. The ELISA sensitivity and specificity to detect EOC were calculated using receiver operating curves. Survival data were calculated using Kaplan Maier curves. RESULTS: Median age at the time of diagnosis was 60years and follow-up ended with a mean of 44.8month. 188 (91%) patients were diagnosed at advanced stages (FIGO III/IV) and 188 patients (91%) suffered from high-grade serous ovarian carcinoma. YB-1/p18 levels were significantly decreased in older patients (p=0.021). Significantly lower serum levels of YB-1/p18 were detected in the EOC cohort when compared to the control group (p<0.0001, AUC=0.827; 95% CI, 0.787 0.867). Using the expression of serum YB-1/p18 in early stages I and II cases these could be differentiated from control cases (p<0.0001, AUC=0.816; 95% CI 0.704-0.929). No other significant associations between clinical prognostic factors and YB-1/p18 serum levels were detected. Immunoblotting results with serum samples suggest that masking of epitopes by the YB-1/p18 fragment in multiprotein-complexes under non reducing conditions leads to the observed reduced ELISA readings in the EOC cohort. CONCLUSIONS: The quantification of fragment YB-1/p18 derived from cold shock protein YB-1 in serum samples could be useful for the early diagnosis of EOC. PMID- 27371775 TI - Salivary levels of inflammatory cytokines and their association to periodontal disease in systemic lupus erythematosus patients. A case-control study. AB - Both Systemic Lupus Erythematosus (SLE) and periodontal disease (PD) present a similar immunological profile mainly characterized by altered cytokine levels. In this study we sought to investigate the salivary levels of inflammatory cytokines and their association with PD in SLE patients. 60 patients with SLE and 54 systemically healthy individuals underwent a full periodontal clinical examination. They were then grouped according to their periodontal status. Stimulated saliva was collected in order to evaluate the salivary levels of interferon (IFN-gamma), Interleukin (IL)-10, IL-17, IL-1beta, and IL-4. Systemically healthy individuals with periodontitis (group P) presented higher levels of cytokines when compared to systemically healthy individuals, with no periodontal disease (group S) (p<0.05). Additionally, in the P group, patients presented similar levels of cytokines to those of the patients with SLE, regardless of the presence of PD (p>0.05), for most of the analyzed cytokines. There was a positive correlation in SLE patients, including IL-1beta and all periodontal clinical parameters (p<0.05), and between IL-4 and gingival bleeding index and the presence of biofilm (p<0.05). Thus, our results confirmed, that patients with PD showed higher salivary levels of cytokines and, in SLE patients, the increased levels of salivary cytokines were observed even in the absence of periodontitis. IL-1beta and IL-4 salivary levels were also positively correlated with periodontal status indicating their potential as markers of the amount and extent of periodontal damage in patients with SLE. PMID- 27371776 TI - Preliminary observations on the association between serum IL-6 and hydration status and cardiovascular risk in patients treated with peritoneal dialysis. AB - INTRODUCTION: Systemic inflammation, as defined by elevated blood IL-6, is a strong independent predictor of peritoneal dialysis (PD) patient survival. The present study has aimed to determine whether there exists a particular "phenotype" associated with high systemic IL-6 that characterizes PD patients in terms of their fluid status and cardiac parameters. METHODS: Fifty-seven prevalent PD patients were classified according to serum concentrations of IL-6. The degree of overhydration was assessed by bioimpedance analysis (BIA). Echocardiography and serum concentrations of NT-proBNP and troponin T were used to assess cardiovascular risk. RESULTS: Patients with high serum IL-6 were older, more often diabetic, treated with PD for longer, and significantly more overhydrated. There was a significant correlation between serum IL-6, hydration status (r=0.38; p=0.002) and serum albumin (r=-0.35; p=0.009). Multivariate regression analysis confirmed a strong association of overhydration, hypoalbuminemia, and systemic IL-6 concentration. Patients with high IL-6 had significantly increased levels of both NT-proBNP (r=0.36; p=0.006) and TnT (r=0.50; p<0.001) in the absence of abnormalities in echocardiography. CONCLUSIONS: High systemic IL-6 identifies PD patients with increased cardiovascular risk that is significantly related to overhydration. Thus, the measurement of serum IL-6 may contribute to the more accurate assessment of cardiovascular status in patients undergoing PD. PMID- 27371777 TI - Editorial Comment. PMID- 27371778 TI - All-cause mortality and its risk factors among type 1 and type 2 diabetes mellitus in a country facing diabetes epidemic. AB - AIM: Diabetes mellitus is associated with an increased risk of premature death mainly secondary to macrovascular and microvascular complications. Mortality data from the Eastern Mediterranean region known for its high diabetes prevalence are lacking. We aimed to assess all-cause mortality and its predictors using large cohort from the Saudi National Diabetes Registry (SNDR). METHODS: The study population comprised of 40,827 individuals with type 1 and type 2 diabetes mellitus aged ?25years registered in SNDR between January 2007 and December 2013. All patients were followed until death, according to the date of death or reaching 100years of age or end of the study. Death was verified from the national civil affairs database. The general population during the study period was used as a reference for standardized mortality ratio (SMR) calculation. RESULTS: With a total of 152,038 person-years of follow up, 2582 patients were deceased giving all-cause mortality rate of 16.98 per 1000 person-years and SMR (95% CI) of 1.93 (1.86-2.00). Mortality rates were higher among men and increased with age, while SMR attenuated with increasing age. The independent predictors for all-cause mortality were longer diabetes duration, presence of macrovascular complications, nephropathy, retinopathy, hypertension, male gender and older age, while morbid obesity and the presence of hyperlipidemia were associated with reduced risk. CONCLUSIONS: The unexpectedly low mortality rate in this population would be associated with higher number of deaths as a result of the high prevalence of diabetes and its complications. Reducing the prevalence of diabetes and its complications would reduce the risk of mortality. PMID- 27371779 TI - Distribution and clinical association of plasma soluble ST2 during the development of type 2 diabetes. AB - AIM: ST2 plays important roles in diabetes and cardiovascular diseases. However, the distribution and changes in plasma soluble ST2 during the development of type 2 diabetes remain unclear. METHODS: In the present study, 525 subjects were recruited and divided into three groups: normal, prediabetic and diabetic subjects. The sST2 levels of all subjects were measured using a high-sensitivity assay. RESULTS: sST2 levels were modestly but significantly elevated in patients with diabetes (26.1ng/ml) compared with normal subjects (19.3ng/ml, P<0.001) and persons with prediabetes (20.3ng/ml, P<0.001). The third and fourth quartiles (21.3 and 29.1ng/ml, respectively) of the sST2 levels were associated with a 2.31 and 4.00-fold increased risk of having diabetes. With the prediabetic group as a reference population, patients with sST2 levels in the fourth quartiles had a higher increased risk of having diabetes mellitus (odds ratios=2.19, P<0.05). Furthermore, each SD log sST2 was associated with a 1.57-fold increased risk of atherosclerosis when all relevant variables was added to the multivariable logistic regression models. After adjustment for age and sex, all markers of liver and renal function, HDL-cholesterol, total cholesterol and smoking status showed a significant association with sST2 levels. CONCLUSION: Elevated sST2 levels were not only associated with metabolic characteristics of diabetes but also with a significantly increased risk of having diabetes. PMID- 27371780 TI - Comparison of screening scores for diabetes and prediabetes. AB - AIMS: There are numerous risk or screening scores for the prediction of type-2 diabetes mellitus (DM). In contrast, few scores are available for preDM. In this paper, we compare the two screening scores from the American Diabetes Association (ADA) and Centers for Disease Control and Prevention (CDC) that can be used for DM as well as preDM. METHODS: Adult participants (N=9391) without known DM from the National Health and Nutrition Examination Surveys 2009-12 were included. We fitted the factors/items in the ADA and CDC scores in logistic regression with the outcomes of undiagnosed DM, preDM, and combination, and assessed the association and discrimination accuracy. We also evaluated the suggested cutpoints that define high risk individuals. We mimicked the original models/settings but also tested various deviations/modifications often encountered in practice. RESULTS: Both scores performed well and robustly, while the ADA score performed somewhat better (e.g., AUC=0.77 for ADA and 0.73-0.74 for CDC for DM; 0.72-0.74 and 0.70-0.71 for preDM). The same predictors and scoring rules seem to be reasonably justified with different cutpoints for DM and preDM, which can make usage easier and consistent. Some factors such as race and HDL/LDL cholesterols may be useful additions to health education. CONCLUSIONS: Current DM education and screening focus on the prevention and management of DM. The ADA and CDC scores could further help when we identify individuals at high risk for preDM, and teach the importance of preDM during which lifestyle intervention can be effective and urgently needed. PMID- 27371781 TI - Frequency of diabetic retinopathy and related factors in patients with diabetes having coronary artery disease. PMID- 27371782 TI - Plasma copeptin in children and adolescents with type 1 diabetes mellitus in comparison to healthy controls. AB - In a cohort of children and adolescents with type 1 diabetes mellitus the trial tested the hypothesis that copeptin levels are associated with kidney function, biometrical data and quality of diabetes control. PATIENTS AND METHODS: A total of 141 subjects were recruited to participate in the trial: 80 patients with type 1 diabetes (13.0+/-3.4years, HbA1c 7.85+/-1.42%) and 61 healthy controls (12.4+/ 2.8years). Clinical and socio-economic data were assessed. A sandwich immunoassay (B.R.A.H.M.S. GmbH/Thermo Fisher Scientific, Hennigsdorf/Berlin, Germany) was used for measuring plasma copeptin levels. RESULTS: The mean concentration of copeptin in the diabetic patients was 4.75+/-3.46pmol/l. There was a strong inverse correlation between copeptin and GFR (r=-0.86, p=0.021), as well as with total cholesterol (r=-0.23, p=0.041), LDL-cholesterol (r=-0.24, p=0.036), but not with serum creatinine, albuminuria, HbA1c, blood glucose, MAGE, CRP, systolic or diastolic blood pressure or age, diabetes duration, weight, height and BMI. Comparing patients with a diabetes duration of ?7years (n=45) with those with a diabetes duration <7years (n=35), patients with a longer duration of diabetes had higher copeptin levels (5.24+/-2.26 vs 4.13+/-2.86, p=0.045). Performing multivariate analyses only GFR could be identified as a parameter associated with copeptin (R-square=0.05, beta=-0.23, p=0.032). In the healthy controls mean copeptin concentration was 5.56+/-3.15pmol/l. The copeptin concentration and GFR were inversely correlated as well (r=-0.61, p=0.034). However, other correlation and multivariate analyses revealed no further significant results. Comparing patients with type 1 diabetes mellitus with the healthy controls, the diabetes patients revealed no significant difference with respect to copeptin (p=0.24), serum creatinine (49.8+/-11.9 vs 50.4+/-11.0MUmol/l, p=0.53) or GFR (102.4+/-23.3 vs 104.5+/-19.1ml/min, p=0.47). On the other hand, patients with type 1 diabetes had lower concentrations of CRP (1.66+/-3.91 vs 3.21+/-3.04MUg/ml, p=0,013), triglycerides (0.88+/-0.53 vs 1.13+/-0.60mmol/l, p=0.010), and a lower ratio of LDL-/HLD-cholesterol (1.73+/-0.69 vs 2.32+/-0.80, p<0.001), as well as lower body weight (51.3+/-18.0 vs 60.3+/-15.7kg, p=0.002) and BMI (19.7+/-3.8 vs 23.2+/ 2.9kg/m(2), p<0.001). In contrast to the controls, the diabetes patients had higher blood glucose levels at the time of examination (8.2+/-3.8 vs 4.7+/ 0.5mmol/l, p<0.001), higher HDL-cholesterol levels (1.59+/-0.34 vs 1.26+/ 0.24mmol/l, p<0.001), as well as higher education and higher educational levels of the mothers. CONCLUSIONS: The present trial revealed a clear association between GFR and copeptin in children and adolescents with type 1 diabetes mellitus. Hence, copeptin can be considered as a marker of renal function. PMID- 27371783 TI - The feasibility of shoulder motion tracking during activities of daily living using inertial measurement units. AB - Measurements of shoulder kinematics during activities of daily living (ADL) can be used to evaluate patient function before and after treatment and help define device testing conditions. The purpose of this study was to demonstrate the feasibility of using wearable inertial measurement units (IMUs) to track shoulder joint angles while performing actual ADLs outside of laboratory simulations. IMU data of 5 subjects with normal shoulders was collected for 4h at the subjects' workplace and up to 4h off-work. An Unscented Kalman Filter (UKF) enhanced with gyroscope bias modeling and zero velocity updates demonstrated an accuracy of about 2 degrees and was used to estimate relative upper arm angles from the IMU data. The overall averaged 95th percentile angles were: flexion 128.8 degrees , abduction 128.4 degrees , and external rotation 69.5 degrees . These peaks angles are similar to other investigator's reports using laboratory simulations of ADLs measured with optical and electromagnetic technologies. Additionally, with a Fourier transform the 50th percentile frequency was determined and used to extrapolate the typical number of arm cycles in a 10year period to be 649,000. Application of the UKF with the additional drift correction made substantial improvements in shoulder tracking performance and this feasibility data suggests that IMUs with the UKF are suitable for extended use outside of laboratory settings. The data provides a novel description of arm motion during ADLs including an estimate for the 10 year cycle count of upper arm motion. PMID- 27371784 TI - Effect of the 6-minute walk test on plantar loading and capability to produce ankle plantar flexion forces. AB - The six-minute walk test (6MWT) is used to evaluate the ambulatory capacity of patients suffering from respiratory disorders, obesity or neuromuscular diseases. Our primary aim was to evaluate the effects of the 6MWT on the postural sway and the ankle plantar flexion forces in healthy subjects. We measured the ankle plantar flexion forces and the plantar contact area before and after a 6MWT in normal weight and overweight subjects with no history of respiratory, cardiac, and neuromuscular disorders. A post-6MWT sensation of bodily fatigue was evaluated by Multidimensional Fatigue Inventory (MFI) and Pichot fatigue scales. A computerized pedobarographic platform was used to collect the mean plantar contact area, the changes of the center of pressure (CoP) surface and its medial and lateral deviations. In a limited number of subjects, the reproducibility of all the measurements was explored. In both groups, the 6MWT elicited a sensation of bodily fatigue. It also significantly reduced the ankle plantar flexion forces, and increased both the mean plantar contact area and the CoP surface, the changes being not apparent after 10min. The post-6MWT lateral CoP deviations were accentuated in normal weight subjects, while an increase in medial CoP deviations occurred in overweight ones. The 6MWT-induced changes in the plantar flexion force and pedobarographic variables were reproducible. Because this study clearly showed some post-6MWT alterations of the subjects' posture sway of our subjects, we questioned the possible mechanisms occurring that could explain the altered muscle force and the transient destabilization of posture after the 6MWT. PMID- 27371786 TI - A novel hybrid MCDM model for performance evaluation of research and technology organizations based on BSC approach. AB - Balanced Scorecard (BSC) is a strategic evaluation tool using both financial and non-financial indicators to determine the business performance of organizations or companies. In this paper, a new integrated approach based on the Balanced Scorecard (BSC) and multi-criteria decision making (MCDM) methods are proposed to evaluate the performance of research centers of research and technology organization (RTO) in Iran. Decision-Making Trial and Evaluation Laboratory (DEMATEL) are employed to reflect the interdependencies among BSC perspectives. Then, Analytic Network Process (ANP) is utilized to weight the indices influencing the considered problem. In the next step, we apply four MCDM methods including Additive Ratio Assessment (ARAS), Complex Proportional Assessment (COPRAS), Multi-Objective Optimization by Ratio Analysis (MOORA), and Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) for ranking of alternatives. Finally, the utility interval technique is applied to combine the ranking results of MCDM methods. Weighted utility intervals are computed by constructing a correlation matrix between the ranking methods. A real case is presented to show the efficacy of the proposed approach. PMID- 27371785 TI - Blueberry inhibits invasion and angiogenesis in 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral squamous cell carcinogenesis in hamsters via suppression of TGF-beta and NF-kappaB signaling pathways. AB - Aberrant activation of oncogenic signaling pathways plays a pivotal role in tumor initiation and progression. The purpose of the present study was to investigate the chemopreventive and therapeutic efficacy of blueberry in the hamster buccal pouch (HBP) carcinogenesis model based on its ability to target TGF-beta, PI3K/Akt, MAPK and NF-kappaB signaling and its impact on invasion and angiogenesis. Squamous cell carcinomas were induced in the HBP by 7,12 dimethylbenz[a]anthracene (DMBA). The effect of blueberry on the oncogenic signaling pathways and downstream events was analyzed by quantitative real-time PCR and immunoblotting. Experiments with the ECV304 cell line were performed to explore the mechanism by which blueberry regulates angiogenesis. Blueberry supplementation inhibited the development and progression of HBP carcinomas by abrogating TGF-beta and PI3K/Akt pathways. Although blueberry failed to influence MAPK, it suppressed NF-kappaB activation by preventing nuclear translocation of NF-kappaB p65. Blueberry also modulated the expression of the oncomiR miR-21 and the tumor suppressor let-7. Collectively, these changes induced a shift to an anti-invasive and anti-angiogenic phenotype as evidenced by downregulating matrix metalloproteinases and vascular endothelial growth factor. Blueberry also inhibited angiogenesis in ECV304 cells by suppressing migration and tube formation. The results of the present study suggest that targeting oncogenic signaling pathways that influence acquisition of cancer hallmarks is an effective strategy for chemointervention. Identification of modulatory effects on phosphorylation, intracellular localization of oncogenic transcription factors and microRNAs unraveled by the present study as key mechanisms of action of blueberry is critical from a therapeutic perspective. PMID- 27371787 TI - Epithelial-mesenchymal transition (EMT) and metastasis: yes, no, maybe? AB - An epithelial to mesenchymal transition (EMT) is a process of cell remodeling critical during embryonic development and organogenesis. During an EMT, epithelial cells lose their polarized organization and acquire migratory and invasive capabilities. While a plethora of experimental results have indicated that manipulating an EMT also affects cancer metastasis, its reverse process, a mesenchymal to epithelial transition (MET), seems to support metastatic outgrowth in distant organs. Moreover, recent reports investigating cancer cells circulating in the blood stream or employing genetic lineage-tracing have questioned a critical role of an EMT in metastasis formation. Hence, we need to better understand the molecular networks underlying the cell plasticity conferred by an EMT or a MET and its functional contribution to malignant tumor progression. PMID- 27371788 TI - Direct correlation of diffusion and pore size distributions with low field NMR. AB - The time-dependent diffusion coefficient (D) is a powerful tool to probe microstructure in porous media, and can be obtained by the NMR method. In a real porous sample, molecular diffusion is very complex. Here we present a new method which directly measures the relationship between effective diffusion coefficients and pore size distributions without knowing surface relaxivity. This method is used to extract structural information and explore the relationship between D and a in porous media having broad pore size distributions. The diffusion information is encoded by the Pulsed Field Gradient (PFG) method and the pore size distributions are acquired by the Decay due to Diffusion in the Internal Field (DDIF) method. Two model samples were measured to verify this method. Restricted diffusion was analyzed, and shows that most fluid molecules experience pore wall. The D(a) curves obtained from correlation maps were fitted to the Pade approximant equation and a good agreement was found between the fitting lines and the measured data. Then a sandstone sample with unknown structure was measured. The state of confined fluids was analyzed and structural information, such as pore size distributions, were extracted. The D - T1 correlation maps were also obtained using the same method, which yielded surface relaxivities for different samples. All the experiments were conducted on 2MHz NMR equipment to obtain accurate diffusion information, where internal gradients can be neglected. This method is expected to have useful applications in the oil industry, particularly for NMR logging in the future. PMID- 27371789 TI - PCDH19-related epilepsy and Dravet Syndrome: Face-off between two early-onset epilepsies with fever sensitivity. AB - Aim of this study is to compare PCDH19-related epilepsy and Dravet Syndrome (DS) in order to find out differences between these two infantile epilepsies with fever sensitivity. We retrospectively reviewed the medical records of 15 patients with PCDH19-related epilepsy and 19 with DS. Comparisons were performed with Fisher's exact test or Student's t-test. Females prevailed in PCDH19-related epilepsy. Epilepsy onset was earlier in DS (5.0+2.1 vs 11.2+7.0months; p<0.05). The second seizure/cluster occurred after a longer latency in PCDH19-related epilepsy rather than in DS (10.1+/-13.6 vs 2.2+/-2.1months; p<0.05). Seizures were mainly single and prolonged seizures in DS, and brief and clustered in PCDH19-related epilepsy. Myoclonic and clonic seizures have been found only in DS. Other types of seizures were found in both epilepsies with a prevalence of GTCS and atypical absences in DS, and focal motor and hypomotor seizures in PCDH19-related epilepsy. Seizures with affective symptoms have been confirmed to be typical of PCDH19-related epilepsy. Status Epilepticus equally occurred in both groups. Photosensitivity was detected only in DS. No differences were found about the presence of intellectual disabilities and behavioral disturbances. We were able to find out some distinctive features, which could address the diagnosis towards DS or PCDH19-related epilepsy, since first manifestation. These considerations suggest to definitively considering PCDH19 gene as cause of a proper epileptic phenotype. PMID- 27371790 TI - Large-scale functional network reorganization in 22q11.2 deletion syndrome revealed by modularity analysis. AB - The 22q11.2 deletion syndrome (22q11DS) is associated with cognitive impairments and a 41% risk of developing schizophrenia. While several studies performed on patients with 22q11DS showed the presence of abnormal functional connectivity in this syndrome, how these alterations affect large-scale network organization is still unknown. Here we performed a network modularity analysis on whole-brain functional connectomes derived from the resting-state fMRI of 40 patients with 22q11DS and 41 healthy control participants, aged between 9 and 30 years old. We then split the sample at 18 years old to obtain two age subgroups and repeated the modularity analyses. We found alterations of modular communities affecting the visuo-spatial network and the anterior cingulate cortex (ACC) in both age groups. These results corroborate previous structural and functional studies in 22q11DS that showed early impairment of visuo-spatial processing regions. Furthermore, as ACC has been linked to the development of psychotic symptoms in 22q11DS, the early impairment of its functional connectivity provide further support that ACC alterations may provide potential biomarkers for an increased risk of schizophrenia. Finally, we found an abnormal modularity partition of the dorsolateral prefrontal cortex (DLPFC) only in adults with 22q11DS, suggesting the presence of an abnormal development of functional network communities during adolescence in 22q11DS. PMID- 27371791 TI - Proteomics study revealed altered proteome of Dichogaster curgensis upon exposure to fly ash. AB - Fly ash is toxic and its escalating use as a soil amendment and disposal by dumping into environment is receiving alarming attention due to its impact on environment. Proteomics technology is being used for environmental studies since proteins respond rapidly when an organism is exposed to a toxicant, and hence soil engineers such as earthworms are used as model organisms to assess the toxic effects of soil toxicants. This study adopted proteomics technology and profiled proteome of earthworm Dichogaster curgensis that was exposed to fly ash, with main aim to elucidate fly ash effects on cellular and metabolic pathways. The functional classification of identified proteins revealed carbohydrate metabolism (14.36%), genetic information processing (15.02%), folding, sorting and degradation (10.83%), replication and repair (3.95%); environmental information processing (2.19%), signal transduction (9.61%), transport and catabolism (17.27%), energy metabolism (6.69%), etc. in the proteome. Proteomics data and functional assays revealed that the exposure of earthworm to fly ash induced protein synthesis, up-regulation of gluconeogenesis, disturbed energy metabolism, oxidative and cellular stress, and mis-folding of proteins. The regulation of ubiquitination, proteasome and modified alkaline comet assay in earthworm coelomocytes suggested DNA-protein cross link affecting chromatin remodeling and protein folding. PMID- 27371792 TI - Improvement in methanol production by regulating the composition of synthetic gas mixture and raw biogas. AB - Raw biogas can be an alternative feedstock to pure methane (CH4) for methanol production. In this investigation, we evaluated the methanol production potential of Methylosinus sporium from raw biogas originated from an anaerobic digester. Furthermore, the roles of different gases in methanol production were investigated using synthetic gas mixtures of CH4, carbon dioxide (CO2), and hydrogen (H2). Maximum methanol production was 5.13, 4.35, 6.28, 7.16, 0.38, and 0.36mM from raw biogas, CH4:CO2, CH4:H2, CH4:CO2:H2, CO2, and CO2:H2, respectively. Supplementation of H2 into raw biogas increased methanol production up to 3.5-fold. Additionally, covalent immobilization of M. sporium on chitosan resulted in higher methanol production from raw biogas. This study provides a suitable approach to improve methanol production using low cost raw biogas as a feed containing high concentrations of H2S (0.13%). To our knowledge, this is the first report on methanol production from raw biogas, using immobilized cells of methanotrophs. PMID- 27371793 TI - A combined sodium phosphate and sodium sulfide pretreatment for enhanced enzymatic digestibility and delignification of corn stover. AB - Na3PO4 and Na2S were employed as efficient alkaline catalysts for the pretreatment of corn stover. To systematically obtain optimal conditions, the effects of critical pretreatment parameters including sodium phosphate concentration (1-4%), sulfidity (0-20%), pretreatment temperature (100-120 degrees C), and reaction time (20-60min) on the reducing sugar yield of pretreated substrates were evaluated in a lab-scale using the response surface methodology. Pretreated under the sodium phosphate concentration of 4%, sulfidity of 10%, temperature of 120 degrees C, and reaction time of 40min, the reducing sugar yield and glucose yield of the pretreated corn stover achieved 91.11% and 64.01%, respectively, with a moderate enzyme loading of 30FPU/g substrate. Additionally, a strong correlation (R(2)=0.971 and R(2)=0.954) between the delignification and the reducing sugar yield (or glucose yield) was observed by this pretreatment method. These results evidently support that the combined Na3PO4-Na2S pretreatment is an effective and feasible method for processing lignocellulosic biomass. PMID- 27371794 TI - Enhanced succinate production from glycerol by engineered Escherichia coli strains. AB - In this study, an engineered strain Escherichia coli MLB (ldhA(-)pflB(-)) was constructed for production of succinate from glycerol. The succinate yield was 0.37mol/mol in anaerobic culture, however, the growth and glycerol consumption rates were very slow, resulting in a low succinate level. Two-stage fermentation was performed in flasks, and the succinate yield reached 0.93mol/mol, but the succinate titer was still low. Hence, overexpression of malate dehydrogenase, malic enzyme, phosphoenolpyruvate (PEP) carboxylase and PEP carboxykinase (PCK) from E. coli, and pyruvate carboxylase from Corynebacterium glutamicum in MLB was investigated for improving succinate production. Overexpression of PCK resulted in remarkable enhancement of glycerol consumption and succinate production. In flask experiments, the succinate concentration reached 118.1mM, and in a 1.5-L bioreactor the succinate concentration further increased to 360.2mM. The highest succinate yield achieved 0.93mol/mol, which was 93% of the theoretical yield, in the anaerobic stage. PMID- 27371795 TI - Co-generation of biohydrogen and biomethane through two-stage batch co fermentation of macro- and micro-algal biomass. AB - Aquatic micro-algae can be used as feedstocks for gaseous biofuel production via biological fermentation. However, micro-algae usually have low C/N ratios, which are not advantageous for fermentation. In this study, carbon-rich macro-algae (Laminaria digitata) mixed with nitrogen-rich micro-algae (Chlorella pyrenoidosa and Nannochloropsis oceanica) were used to maintain a suitable C/N ratio of 20 for a two-stage process combining hydrogen and methane fermentation. Co fermentation of L. digitata and micro-algae facilitated hydrolysis and acidogenesis, resulting in hydrogen yields of 94.5-97.0mL/gVS; these values were 15.5-18.5% higher than mono-fermentation using L. digitata. Through the second stage of methane co-fermentation, a large portion of energy remaining in the hydrogenogenic effluents was recovered in the form of biomethane. The two-stage batch co-fermentation markedly increased the energy conversion efficiencies (ECEs) from 4.6-6.6% during the hydrogen fermentation to 57.0-70.9% in the combined hydrogen and methane production. PMID- 27371796 TI - Thermo-chemical pretreatment of rice straw for further processing for levulinic acid production. AB - A variety of pretreatment protocols for rice straw fiber reconstruction were evaluated under mild conditions (upto 0.2%wt. and 121 degrees C) with the object of improving polymer susceptibility to chemical attack while preserving carbohydrate sugars for levulinic acid (LA) production. Each of the protocols tested significantly enhanced pretreatment recoveries of carbohydrate sugars and lignin, and a NaOH protocol showed the most promise, with enhanced carbohydrate preservation (upto 20% relative to the other protocols) and more effective lignin dissolution (upto 60%). Consequently, post-pretreatment fibers were evaluated for LA preparation using an existing co-solvent system consisting of HCl and THF, in addition supplementation of DMSO was attempted, in order to improve final product recovery. In contrast to pretreatment response, H2SO4 protocol fibers yielded highest LA conc. (21%wt. with 36% carbohydrate conversion efficiency) under the modest reaction conditions. Apparent spectroscopic analysis witnessed for fiber destruction and delocalization of inherent constituents during pretreatment protocols. PMID- 27371797 TI - Structural changes and enzymatic response of Napier grass (Pennisetum purpureum) stem induced by alkaline pretreatment. AB - Napier grass is a promising energy crop in the tropical region. Feasible alkaline pretreatment technologies, including NaOH, Ca(OH)2, NH3, and alkaline H2O2 (aH2O2), were used to delignify lignocellulose with the aim of improving glucose recovery from Napier grass stem cellulose via enzymatic saccharification. The influences of the pretreatments on structural alterations were examined using SEM, FTIR, XRD, and TGA, and the relationships between these changes and the enzymatic digestibility of cellulose were addressed. The extensive removal of lignin (84%) in NaOH-pretreated fibre agreed well with the high glucan conversion rate (94%) by enzymatic hydrolysis, while the conversion rates for fibre pretreated with Ca(OH)2, NH3, and aH2O2 approached 60%, 51%, and 42%, respectively. The substantial solubilisation of lignin created porosity, allowing increased cellulose accessibility to cellulases in NaOH-pretreated fibre. In contrast, high lignin content, lignin redeposition on the surface, and residual internal lignin and hemicellulose impeded enzymatic performance in Ca(OH)2-, NH3 , and aH2O2-pretreated fibres, respectively. PMID- 27371798 TI - A multi-technique approach for detecting and evaluating material inconsistencies in historical banknotes. AB - The identification of forged and genuine historical banknotes is an important problem for private collectors and researchers responsible for the care of numismatic collections. This paper presents a research approach for detecting material differences in historical banknotes through the use of microfading spectrometry along with other techniques such as hyperspectral image analysis, Fourier-transform infrared spectroscopy, and X-ray fluorescence spectrometry. Microfading spectrometry results showed higher sensitivity to light irradiation for an overprint ink used on a suspicious banknote relative to its counterparts. In addition, the spectrocolorimetric changes experienced by the paper substrates during microfade testing also provided a way for discriminating between two groups of banknotes. These variations have been confirmed after analyzing the spectral and physico-chemical data obtained using the abovementioned complementary techniques. PMID- 27371799 TI - Elevation of post mortem vitreous humour sodium and chloride levels can be used as a reliable test in cases of suspected salt water drowning when the immersion times are less than one hour. AB - BACKGROUND: Previous studies in salt water drowning deaths (SWD) demonstrated an observable elevation of post mortem vitreous sodium and chloride (PMVSC) levels. It remains unclear what the underlying mechanism responsible for this change is: whether this is due to rapid electrolyte changes from salt water inhalation/ingestion during drowning or from electrolyte diffusion and/or osmosis across the outer coats of the eyeballs during immersion. A recent animal study using sacrificed bovine eyeballs immersed in salt water demonstrated no significant elevations in PMVSC when immersed for less than one hour. Assuming similar physical properties between human and bovine, we extrapolate that an elevation in PMVSC in SWD with immersion times of less than one hour (SWD-1) would not be from immersion, but from drowning. AIM: Investigate whether there is an elevation in PMVSC in SWD-1. METHODS: Retrospective study comparing PMVSC in SWD-1 with controls from 2012 to 2015 inclusive. RESULTS: PMVSC in SWD-1 was significantly elevated compared with controls. A PMVSC of 259mmol/L has a sensitivity, specificity and likelihood ratio of 0.9, 0.9 and 7.6, respectively. CONCLUSION: The elevation in PMVSC in SWD-1 is due to drowning. A PMVSC of 259mmol/L and above is a reliable ancillary test in diagnosing drowning in bodies immersed in salt water for less than one hour. PMID- 27371800 TI - Childhood trauma, PTSD, and psychosis: Findings from a highly traumatized, minority sample. AB - Trauma, especially early life trauma, is a risk factor for the development of both posttraumatic stress disorder and psychosis. The goal of the present study was to determine specific associations between exposure to childhood abuse, PTSD symptoms, and current psychotic disorder. Subjects were recruited from a public, urban hospital (N=328, >90% African American). Psychotic disorders were measured using the MINI International Neuropsychiatric Interview, PTSD was measured using the Clinician Administered PTSD Scale, child abuse was measured with the Childhood Trauma Questionnaire, and lifetime trauma exposure was measured with the Traumatic Events Inventory. Logistic regression analyses showed that both child abuse and current PTSD were statistically significant predictors of psychotic disorder beyond the effects of lifetime trauma load. When PTSD symptom clusters were examined, avoidance and numbing symptoms showed unique association with psychotic disorder independent of demographic variables and trauma exposure. Using bootstrapping techniques, we found a full indirect effect of PTSD on the association between child abuse and, suggesting a particularly important role of PTSD symptoms in relation to psychotic disorder in the presence of early life trauma. Because this is a cross-sectional study, continued research is needed to determine causality of such models. Identifying co-occurring psychosis and PTSD, particularly in populations with high levels of trauma exposure, is critical and will likely aid in more successful treatment interventions. PMID- 27371801 TI - An international study of hospitalized cancer patients' health status, nursing care quality, perceived individuality in care and trust in nurses: A path analysis. AB - BACKGROUND: Providing high quality nursing care for patients with malignancies is complex and driven by many factors. Many of the associations between nursing care quality, trust, health status and individualized care remain obscure. OBJECTIVE: To empirically test a model of association linking hospitalized cancer patients' health status, nursing care quality, perceived individuality in care and trust in nurses. DESIGN: A cross-sectional, exploratory and correlational study design was used. SETTINGS: This multi-site study was conducted in cancer care clinics, in patient wards of five tertiary care hospitals in Cyprus, Finland, Greece and Sweden. SAMPLE: Out of 876 hospitalized patients with a confirmed histopathological diagnosis of cancer approached to participate in the study in consecutive order, 599 (response rate 68%) agreed to participate and the data from 590 were used for path analysis. METHODS: Data were collected in 2012-2013 with the Individualized Care Scale-Patient (ICS-Patient), the Oncology Patients' Perceptions of Quality Nursing Care Scale (OPPQNCS), the Euro-Qol (EQ-5D-3L) and the Trust in Nurses Scale. Data were analysed statistically using descriptive and inferential statistics. Mplus version 7.11 was used to determine the best Trust model with path analysis. RESULTS: Although the model fit indices suggested that the hypothesized model did not perfectly to the data, a slightly modified model which includes the reciprocal path between individualized care and nursing care quality demonstrated a good fit. CONCLUSION: A model of trust in nurses was developed. Health status, individualized care, and nursing care quality were found to be associated with trust. The model highlights the complexity of caring for cancer patients. Trust in nurses is influenced by the provision of individualized care. Generating and promoting trust requires interventions, which promote nursing care quality, individuality and patients' health status. PMID- 27371802 TI - Positive association between trait impulsivity and high gambling-related cognitive biases among college students. AB - The present study examined whether people with high gambling-related cognitive bias are more likely to have higher levels of impulsivity than are those with low gambling-related cognitive bias. We used Barratt Impulsiveness Scale version 11, Zuckerman-Kuhlman Personality Questionnaire and the Iowa gambling task to explore differences in impulsivity between high and low gambling-related cognitive bias groups. Extreme group design was applied. 110 participants (high gambling related cognition group=58, low one=52) were recruited to complete the gambling related cognition scale, impulsivity self-rating scales and Iowa gambling task. Impulsivity self-rating scores were higher among subjects with high than among those with low gambling-related cognitive bias. Compared with individuals with low gambling-related cognitive bias, those with high levels of such bias showed greater degrees of trait impulsivity. We are unable to identify group differences on IGT. State and trait impulsivity may be dissociated. PMID- 27371803 TI - Risk-taking behavior and impulsivity among HCV-infected patients. AB - The association between risk behaviors and hepatitis C virus (HCV) has been extensively studied. It is also proved that impulsivity is associated with risk behaviors. However, there is a lack of studies investigating the association between HCV and impulsivity, a characteristic that can contribute directly to these risk behaviors. This study aimed to investigate HCV-infected individuals' impulsivity and whether this feature mediates risk behavior. Adult patients with liver diseases (n=269) were divided into two groups: viral group (n=157) - patients with HCV and nonviral group (n=112). Risk behaviors were evaluated by a sociodemographic questionnaire. Impulsivity was assessed through Barratt Impulsiveness Scale - BIS-11. Psychiatric comorbidities were investigated by the Mini International Neuropsychiatric Interview 5.0.0. The viral group patients had higher impulsivity than the nonviral group in all domains: attentional impulsivity, motor impulsivity, and nonplanning. Risk behaviors were also shown to be associated with impulsivity levels. Our results suggest that HCV-infected patients are more impulsive than individuals with other liver diseases, even when analyses are controlled for the presence of comorbid mental disorders. In addition, at-risk behavior was significantly mediated by impulsivity. PMID- 27371804 TI - Advanced age and decisional capacity: The effect of age on the ability to make health care decisions. AB - OBJECTIVE: Cognitive disorders, including dementia, have been shown to be predictors of decisional incapacity, even more than psychotic or substance use disorders. Nonetheless, the impact of advanced age on decisional capacity remains understudied. METHOD: Out of more than 2500 consecutive psychiatric consultations performed by the Consultation-Liaison service at Bellevue Hospital Center in New York City, 266 completed decisional capacity assessments were identified and analyzed with respect to the indications for referral and the impact of age and other sociodemographic, medical and psychiatric variables on decisional capacity. RESULTS: By itself, in this sample advanced age was not associated with impaired medical decision-making. In individuals >=65years old, among whom only 27% were deemed to have decisional incapacity, cognitive disorders including dementia remained the strongest association with this incapacity; meanwhile, in patients <65, decisional impairment was evident in 62%, and delirium, psychosis and neurological disorders caused more decisional impairment. The main indications for referral were placement refusals in those >=65, while young patients were largely seen due to their desire to leave the hospital against medical advice. CONCLUSION: Advanced age by itself failed to be associated with decisional incapacity in this sample. In those >=65, cognitive disorders remained the main association with such incapacity, versus psychosis, substance use and neurological disorders in younger patients. PMID- 27371805 TI - Interaction of single-walled carbon nanotubes and saxitoxin: Ab initio simulations and biological responses in hippocampal cell line HT-22. AB - Saxitoxins (STXs) are potent neurotoxins that also induce cytotoxicity through the generation of reactive oxygen species. Carbon nanotubes (CNTs) are nanomaterials that can promote a Trojan horse effect, facilitating the entry of toxic molecules to cells when adsorbed to nanomaterials. The interaction of pristine single-walled (SW)CNTs and carboxylated (SWCNT-COOH) nanotubes with STX was evaluated by ab initio simulation and bioassays using the cell line HT-22. Cells (5 * 104 cells/mL) were exposed to SWCNT and SWCNT-COOH (5 MUg mL-1 ), STX (200 MUg L-1 ), SWCNT+STX, and SWCNT-COOH+STX for 30 min or 24 h. Results of ab initio simulation showed that the interaction between SWCNT and SWCNT-COOH with STX occurs in a physisorption. The interaction of SWCNT+STX induced a decrease in cell viability. Cell proliferation was not affected in any treatment after 30 min or 24 h of exposure (p > 0.05). Treatment with SWCNT-COOH induced high reactive oxygen species levels, an effect attenuated in SWCNT-COOH+STX treatment. In terms of cellular oxygen consumption, both CNTs when coexposed with STX antagonize the toxin effect. Based on these results, it can be concluded that the results obtained in vitro corroborate the semiempirical evidence found using density functional theory ab initio simulation. Environ Toxicol Chem 2017;36:1728-1737. (c) 2016 SETAC. PMID- 27371806 TI - Acetylshikonin inhibits growth of oral squamous cell carcinoma by inducing apoptosis. AB - OBJECTIVES: Recently, shikonin derivatives from Lithospermum erythrorhizon have been suggested as potential chemotherapeutic agents against numerous types of cancers in addition to their traditional uses, e.g., as anti-inflammatory agents. Acetylshikonin, one of shikonin derivatives, has also been reported to possess anticancer activity. However, few studies of the effectiveness of acetylshikonin against cancer cells have been conducted, and there are no studies of oral cancers. In this study, we investigated the usefulness of acetylshikonin as a treatment regimen for oral cancers by observing the growth inhibitory function of acetylshikonin and the involved mechanisms. DESIGNS: The viability, cell cycle, and ratio of apoptotic cells of oral squamous cell carcinoma (OSCC) cells were observed after treatment with acetylshikonin using MTT assay, flow cytometric analysis, and Annexin V/PI staining, respectively. In addition, molecular changes of apoptosis-related pathways and the role of reactive oxygen species (ROS) were analyzed in acetylshikonin-treated cells. RESULTS: We observed that acetylshikonin significantly suppressed the growth of OSCC cells by inducing apoptotic cell death, and acetylshikonin affected the viability of a normal keratinocyte cell line HaCaT to a lesser degree, suggesting that acetylshikonin may be a good chemotherapeutic reagent with less toxicity to normal tissues. In addition, we found that acetylshikonin-induced apoptosis of OSCC cells is mediated by ROS as well as G2 cell cycle arrest. ROS production in response to acetylshikonin treatment enhanced the phosphorylation of JNK and p38 MAPK, which are in the major pathways of apoptotic cell death mechanisms. CONCLUSIONS: In summary, our data suggest that acetylshikonin is a strong candidate for use as a selective chemotherapeutic agent for the treatment of OSCC. PMID- 27371807 TI - Dental pulp cells promote the expression of receptor activator of nuclear factor kappaB ligand, prostaglandin E2 and substance P in mechanically stressed periodontal ligament cells. AB - OBJECTIVE: This study investigated the expression of receptor activator of nuclear factor-kappaB ligand (RANKL) in periodontal ligament (PDL) cells co cultured with dental pulp (DP) cells following mechanical stress in vitro. Furthermore, the expression of prostaglandin (PG) E2 and substance P (SP) by the PDL cells and by the DP cells were also examined. DESIGN: PDL and DP cells were obtained from 10 rats. The experimental group consisted of PDL cells subjected to centrifugal force as mechanical stress and co-cultured with DP cells. The 3 control groups of PDL cells were: 1) PDL cells without mechanical stress, 2) PDL cells treated with mechanical stress and 3) PDL cells co-cultured with DP cells. The 2 control groups of DP cells were: 1) DP cells without mechanical stress and 2) DP cells co-cultured with PDL cells. In each group, both cells were examined at day 1 and day 3, and mRNA levels of RANKL by PDL cells were analyzed using Real time quantitative Reverse Transcription (RT)-PCR. Furthermore, RANKL expression was observed using Immunofluorescence staining. PGE2 and SP expression levels by PDL cells and DP cells were characterized by ELISA analysis. RESULTS: The expression of RANKL by PDL cells under mechanical stress increased by co culture with DP cells. PGE2 and SP expressions were increased in the group of PDL cells subjected to mechanical stress and co-cultured with DP cells. CONCLUSION: DP cells may facilitate the expression of RANKL in PDL cells under mechanical stress via PGE2 and SP. PMID- 27371809 TI - The role of mating in oviduct biology. AB - The oviduct connects the ovary to the uterus, and is subject to changes that influence gamete transport, fertilization, and early embryo development. The ovarian steroids estradiol and progesterone are largely responsible for regulating oviduct function, although mating signals also affect the female reproductive tract, both indirectly, through sensory stimulation, and directly, through contact with seminal plasma or spermatozoa. The resulting alterations in gene and protein expression help establish a microenvironment that is appropriate for sperm storage and selection, embryo development, and gamete transport. Mating may also induce the switch from a non-genomic to a genomic pathway of estradiol accelerated oviduct egg transport, reflecting a novel example of the functional plasticity in well-differentiated cells. This review highlights the physiological relevance of various aspects of mating to oviduct biology and reproductive success. Expanding our knowledge of the mating-associated molecular and cellular events in oviduct cells would undoubtedly facilitate new therapeutic strategies to treat infertility attributable to oviduct pathologies. Mol. Reprod. Dev. 83: 875-883, 2016 (c) 2016 Wiley Periodicals, Inc. PMID- 27371808 TI - Creation of a protective pulmonary bioshield against inhaled organophosphates using an aerosolized bioscavenger. AB - In addition to the global use of organophosphate (OP) pesticides for agriculture, OP nerve agents and pesticides have been employed on battlefields and by terrorists (e.g., a recent sarin attack in Syria). These occurrences highlight the need for an effective countermeasure against OP exposure. Human butyrylcholinesterase (HuBChE) is a leading candidate, but injection of the high doses required for protection present pharmacokinetic challenges. An aerosolized recombinant form (aer-rHuBChE) that can neutralize inhaled OPs at the portal of entry has been assessed for its efficacy in protecting macaques against respiratory toxicity following inhalation exposure to the pesticide paraoxon (aer Px). While protection in macaques has been demonstrated using the MicroSprayer(r) delivery device, administration to humans will likely employ a vibrating mesh nebulizer (VMN). Compared to the 50-70% lung deposition achieved in adult humans with a VMN, deposition in macaques is <5%, an initial major obstacle to demonstrating protection. Such problems have been partly overcome by using a more efficient modified VMN and proportionally higher doses, which together generate an effective rHuBChE pulmonary bioshield and protect against high levels of inhaled Px. PMID- 27371810 TI - Is Cumulative Exposure to Suicide Attempts and Deaths a Risk Factor for Suicidal Behavior Among Firefighters? A Preliminary Study. AB - The association between cumulative exposure to suicide attempts and deaths and suicidal behavior was examined in a sample of 61 professional firefighters. On average, firefighters reported 13.1 (SD = 16.6) exposures over the course of their lifetime. Cumulative exposure to suicide attempts and deaths was positively correlated with suicidal behavior (r = .38, p = .004). Moreover, firefighters with 12+ exposures were more likely to screen positive for risk of suicidal behavior (OR = 7.885, p = .02). Additional research on the potential impact of cumulative exposure to suicide attempts and deaths on firefighters' health and safety is needed. PMID- 27371812 TI - Increased autumn rainfall disrupts predator-prey interactions in fragmented boreal forests. AB - There is a pressing need to understand how changing climate interacts with land use change to affect predator-prey interactions in fragmented landscapes. This is particularly true in boreal ecosystems facing fast climate change and intensification in forestry practices. Here, we investigated the relative influence of autumn climate and habitat quality on the food-storing behaviour of a generalist predator, the pygmy owl, using a unique data set of 15 850 prey items recorded in western Finland over 12 years. Our results highlighted strong effects of autumn climate (number of days with rainfall and with temperature <0 degrees C) on food-store composition. Increasing frequency of days with precipitation in autumn triggered a decrease in (i) total prey biomass stored, (ii) the number of bank voles (main prey) stored, and (iii) the scaled mass index of pygmy owls. Increasing proportions of old spruce forests strengthened the functional response of owls to variations in vole abundance and were more prone to switch from main prey to alternative prey (passerine birds) depending on local climate conditions. High-quality habitat may allow pygmy owls to buffer negative effects of inclement weather and cyclic variation in vole abundance. Additionally, our results evidenced sex-specific trends in body condition, as the scaled mass index of smaller males increased while the scaled mass index of larger females decreased over the study period, probably due to sex-specific foraging strategies and energy requirements. Long-term temporal stability in local vole abundance refutes the hypothesis of climate-driven change in vole abundance and suggests that rainier autumns could reduce the vulnerability of small mammals to predation by pygmy owls. As small rodents are key prey species for many predators in northern ecosystems, our findings raise concern about the impact of global change on boreal food webs through changes in main prey vulnerability. PMID- 27371813 TI - Contrasting habitat selection amongst cephalopods in the Mediterranean Sea: When the environment makes the difference. AB - Conservation of fish habitat requires a deeper knowledge of how species distribution patterns are related to environmental factors. Habitat suitability modelling is an essential tool to quantify species' realised niches and understand species-environment relationships. Cephalopods are important players in the marine food web and a significant resource for fisheries; they are also very sensitive to environmental changes. Here a time series of fishery independent data (1998-2011) was used to construct habitat suitability models and investigate the influence of environmental variables on four commercial cephalopods: Todaropsis eblanae, Illex coindetii, Eledone moschata and Eledone cirrhosa, in the central Mediterranean Sea. The main environmental predictors of cephalopod habitat suitability were depth, seafloor morphology, chlorophyll-a concentration, sea surface temperature and surface salinity. Predictive maps highlighted contrasting habitat selection amongst species. This study identifies areas where the important commercial species of cephalopods are concentrated and provides significant information for a future spatial based approach to fisheries management in the Mediterranean Sea. PMID- 27371811 TI - Inflammatory Markers and the Risk of Hip and Vertebral Fractures in Men: the Osteoporotic Fractures in Men (MrOS). AB - Cytokines play major roles in regulating bone remodeling, but their relationship to incident fractures in older men is uncertain. We tested the hypothesis that men with higher concentrations of pro-inflammatory markers have a higher risk of fracture. We used a case-cohort design and measured inflammatory markers in a random sample of 961 men and in men with incident fractures including 120 clinical vertebral, 117 hip, and 577 non-spine fractures; average follow-up 6.13 years (7.88 years for vertebral fractures). We measured interleukin (IL)-6, C reactive protein (CRP), tumor necrosis factor alpha (TNFalpha), soluble receptors (SR) of IL-6 (IL-6SR) and TNF (TNFalphaSR1 and TNFalphaSR2), and IL-10. The risk of non-spine, hip, and clinical vertebral fracture was compared across quartiles (Q) of inflammatory markers using Cox proportional hazard models with tests for linear trend. In multivariable-adjusted models, men with the highest (Q4) TNFa cytokine concentrations and their receptors had a 2.0-4.2-fold higher risk of hip and clinical vertebral fracture than men with the lowest (Q1). Results were similar for all non-spine fractures, but associations were smaller. There was no association between CRP and IL-6SR and fracture. Men in the highest Q of IL-10 had a 49% lower risk of vertebral fracture compared with men in Q1. Among men with >=3 inflammatory markers in the highest Q, the hazard ratio (HR) for hip fractures was 2.03 (95% confidence interval [CI] 1.11-3.71) and for vertebral fracture 3.06 (1.66-5.63). The HRs for hip fracture were attenuated by 27%, 27%, and 15%, respectively, after adjusting for appendicular lean mass (ALM), disability, and bone density, suggesting mediating roles. ALM also attenuated the HR for vertebral fractures by 10%. There was no association between inflammation and rate of hip BMD loss. We conclude that inflammation may play an important role in the etiology of fractures in older men. (c) 2016 American Society for Bone and Mineral Research. PMID- 27371814 TI - Stable patients and patients with advanced disease: consensus definitions to support sustained scale up of antiretroviral therapy. AB - OBJECTIVE: As guidelines are evolving towards recommending starting antiretroviral therapy (ART) in all HIV-positive individuals irrespective of clinical and immunological status, HIV programmes will be challenged to manage an increasingly diverse set of patient needs. To support global guideline recommendations for differentiated service delivery, WHO developed consensus definitions for two distinct patient populations: patients presenting with advanced disease and patients who are stable on ART. METHODS: An expert panel consisting of 73 respondents from 28 countries across all six WHO regions supported the development of these definitions. The panel included clinicians, researchers, programme managers, technical advisors and patient group representatives. RESULTS: Patients presenting with advanced disease at presentation to care were defined as CD4 count <200 CD4 cells/mm(3) or WHO Stage III & IV defining illness. Patients stable on ART were defined as those who were receiving ART for at least 1 year with no adverse drug reactions requiring regular monitoring, no current illnesses or pregnancy, a good understanding of lifelong adherence, and evidence of treatment success. Treatment success was defined as two consecutive undetectable viral load measures or, in the absence of viral load monitoring, rising CD4 counts or CD4 counts above 200 cells/mm(3) and an objective adherence measure. CONCLUSIONS: Patients who are stable on ART should be offered a less intensive care package that can lead to improved outcomes while saving resources, including less frequent clinic visits, out-of clinic drug refills and reduced laboratory monitoring. This will allow for clinic resources to be directed towards reducing morbidity and mortality among patients presenting with advanced disease. PMID- 27371815 TI - Identification, Response, and Referral of Suicidal Youth Following Applied Suicide Intervention Skills Training. AB - Gatekeeper training is a public health approach to suicide prevention that encourages community members to identify those at risk for suicide, respond appropriately, and refer for clinical services. Despite widespread use, few studies have examined whether training results in behavior change in participants. This study employed a naturalistic pre-post design to follow 434 participants in Applied Suicide Intervention Skills Training, finding small but significant increases in self-reported identification of at-risk youth, some helpful responses to youth, and numbers of youth referred to treatment from pre test to 6- to 9-month follow-up. Changes in active listening and helping behaviors meant to support treatment referrals (such as convincing a youth to seek treatment) were not observed over time. Additional analyses explored predictors of self-reported skill utilization including identification as a "natural helper" and attitudes about suicide prevention. PMID- 27371816 TI - Charge carrier mobilities in organic semiconductor crystals based on the spectral overlap. AB - The prediction of substance-related charge-transport properties is important for the tayloring of new materials for organic devices, such as organic solar cells. Assuming a hopping process, the Marcus theory is frequently used to model charge transport. Here another approach, which is already widely used for exciton transport, is adapted to charge transport. It is based on the spectral overlap of the vibrational donor and acceptor spectra. As the Marcus theory it is derived from Fermi's Golden rule, however, it contains less approximations, as the molecular vibrations are treated quantum mechanically. In contrast, the Marcus theory reduces all vibrational degrees of freedom to one and treats its influence classically. The approach is tested on different acenes and predicts most of the experimentally available hole mobilities in these materials within a factor of 2. This represents a significant improvement to values obtained from Marcus theory which is qualitatively correct but frequently overestimates the mobilities by factors up to 10. Furthermore, the charge-transport properties of two derivatives of perylene bisimide are investigated. (c) 2016 Wiley Periodicals, Inc. PMID- 27371817 TI - Metabolomic analysis of glycerophospholipid signatures of inflammation treated with non-steroidal anti-inflammatory drugs-induced-RAW264.7 cells using (1)H NMR and U-HPLC/Q-TOF-MS. AB - Non-destructive proton nuclear magnetic resonance ((1)H NMR) spectroscopy and highly sensitive ultra-performance liquid chromatography quadrupole time-of flight mass spectrometry (U-HPLC/Q-TOF-MS) coupled to data processing methods were applied to analyze the metabolic profiling changes of glycerophospholipids (GPLs) in RAW264.7 cells from inflammation to prognosis. Analysis of (1)H NMR was shown that the models were grouped successfully, illustrating that all of them had significant differences. Based on the highly simple, accurate, non-targeted and non-destructively advantages of (1)H NMR, it could be used as a new screening tool of anti-inflammatory drugs in the metabolic profiling of GPLs. 58 GPLs were identified by U-HPLC/Q-TOF-MS, and 19 components were firstly identified in this study compared with our previous results. In addition, ten potential biomarkers were proved, of which phosphatidylcholine (PC) (16:0/18:1) and (18:0/18:1) changed consistently in three drug-induced groups and might be the important biomarkers. Compared with (1)H NMR, U-HPLC/Q-TOF-MS showed higher sensitivity and specificity and was more suitable for the determination of biomarkers apart from the deficiency of time-consuming sample preparation steps and unambiguous metabolite identification. Therefore, it is feasible to analyze the changes of GPLs during inflammation by combining (1)H NMR spectroscopy with U-HPLC/Q-TOF-MS. The metabolic profiling of GPLs provides valuable evidence for inflammation diagnosis and prognosis, and might unravel the mechanisms involved in inflammation progression. PMID- 27371818 TI - Design considerations for patient-specific surgical templates for total hip arthroplasty with respect to acetabular cartilage. AB - Patient-specific instruments (PSIs) are clinically used to support the surgeon during a planned intervention. The planning is typically done based on volumetric image data from medical imaging systems, e.g. computed tomography (CT). The PSI uses the known surface structure of a bone for orientation during the intervention. Some surfaces of human bone are covered with a layer of cartilage which is hardly visible in clinically applied CT-imaging. This experimental study investigates ten different PSI designs and their effect to the overall accuracy when neglecting the cartilage in the design process. Therefore, a model of an acetabulum is used to simulate the use case of PSI in total hip arthroplasty. The concept of the different designs is to create structural elasticities in the PSI to avoid shifting of the whole instrument and rather have a small part of it deformed by cartilage. A needle array structure, for instance, should also be able to oust or penetrate remaining soft tissue in the acetabulum. PMID- 27371819 TI - The nurse-patient communication: voices from nursing students. AB - BACKGROUND: Effective communication skills have been found to be one of the pivotal factors in building positive interpersonal relationships. Little is known about nursing undergraduates' perspectives on communicating with patients. OBJECTIVE: This study aimed to explore nursing students' perspectives and experiences of nurse-patient communication in their clinical placement. METHODS: The participants included 21 second-year undergraduates and 21 first-year master's students. Interviews were conducted in Cantonese and then transcribed in Chinese and translated into English. A content analysis approach was adopted to analyze the data. RESULTS: Five themes emerged from the interview data. 'The necessity of nurse-patient communication' reveals why the students valued nurse patient communication. 'The conversation contents' describes the content of the conversations that students typically had with patients. The third theme is 'self reflection on the nurse-patient communication'. The last two themes, 'the communication pattern in different hospital settings' and 'the obstacles impeding nurse-patient communication', are about the students' communication styles in different hospitals and the barriers they encounter. DISCUSSION: To improve students' communication skills, educators and clinical staff should listen to students, enhance students' reflective skills and strengthen their confidence. CONCLUSION: Through understanding students' difficulties in the nurse-patient communication experience and the skills that they lack, educators can provide them with helpful recommendations to improve their communication skills in clinical practice. PRACTICE IMPLICATIONS: The results of this study reveal that students' nurse-patient communication skills need to be improved. PMID- 27371820 TI - Optimizing enrollment in pediatric obese patients: reflections on recruitment characteristics. AB - Clinical research involving children and adolescents with obesity is challenging due to recruitment, transportation barriers, parents/guardians working multiple jobs and the need to coordinate the schedule of the participant and the parent/guardian. We describe recruitment efforts and successes for a longitudinal observational study of adolescents with obesity. PMID- 27371821 TI - Antithrombotic and cytotoxic activities of four Bangladeshi plants and PASS prediction of their isolated compounds. AB - BACKGROUND: This study aims to investigate whether tested organic extracts possess antithrombotic properties with minimal or no toxicity and to predict the activity of some of their isolated compounds. METHODS: An in vitro thrombolytic model was used to check the clot lysis effect of four Bangladeshi herbal extracts viz., roots of Curculigo recurvata W.T. Aiton (Satipata), leaf of Amorphophallus bulbifer Roxb. (Olkachu), leaf of Phyllanthus sikkimensis Muell. Arg., and whole plant of Thunbergia grandiflora Roxb. (Nillata) using streptokinase as a positive control and water as a negative control. Cytotoxicity was screened by brine shrimp lethality bioassay using vincristine sulfate as positive control. In silico prediction of activity spectra for substances (PASS) prediction was applied for phytoconstituents, namely, nyasicoside, glucomannan, grandifloric acid, serine, and alanine. RESULTS: Using an in vitro thrombolytic model, C. recurvata, A. bulbifer, P. sikkimensis, and T. grandiflora showed 28.10+/-1.64%, 42.47+/-1.96%, 32.86+/-1.92%, and 25.51+/-1.67% of clot lysis, respectively. Reference drug streptokinase exhibited 75.00+/-3.04% clot lysis. Examined herbs showed significant (p<0.001) percentage (%) of clot lysis compared to negative control. In brine shrimp cytotoxic assay, C. recurvata, A. bulbifer, P. sikkimensis, and T. grandiflora showed LC50 values 210.64+/-3.44, 98.51+/-1.47, 187.29+/-2.01, and 386.43+/-3.02 MUg/mL, respectively, with reference to vincristine sulfate (LC50 0.76+/-0.04). PASS predicted that examined phytoconstituents have a wide range of biological activity. CONCLUSIONS: Through our study it was found that A. bulbifer and P. sikkimensis could be considered as very promising and beneficial thrombolytic agents. PMID- 27371822 TI - Age-dependent features of CYP3A, CYP2C, and CYP2E1 functioning at metabolic syndrome. AB - BACKGROUND: Complex investigations of cytochrome P450 (CYP) isoforms with metabolic syndrome (MS) development are limited, and specific features of adolescent's metabolisms are generally disregarded. The aim of present study was a comparative estimation of MS-mediated changes in CYP3A, CYP2C, and CYP2E1 mRNA expression and enzymatic activities, as well as antioxidant system parameters of adult and pubertal rats. METHODS: Wistar albino male rats of two age categories [young animals of 21 days age (50-70 g) and adults (160-180 g)] were divided into four groups (eight animals in each group): (1) control 1 (intact young rats), (2) control 2 (intact adult rats), (3) MS3 (young rats with MS), and (4) MS4 (adult rats with MS). The MS was induced by full replacement of drinking water by 20% fructose solution (200 g/L). After 60 days of MS modeling, the investigation of rat liver CYP3A, CYP2C, and CYP2E1 mRNA expressions, their enzyme-marker activities, as well as the antioxidant system parameters was conducted. RESULTS: Levels of liver CYP2E1 mRNA expression increased with MS: 40% (adults) and 80% (pubertal rats). Pubertal rats had also increased CYP3A2 mRNA expression (30%) and decreased CYP2C mRNA expression (30%). Changes in CYP2E1 and CYP2C enzymatic activities were consistent with the changes of corresponding gene expressions at both age-groups with MS. Simultaneously, liver reduced glutathione contents, and glutathione transferase and reductase activities were decreased in pubertal animals. CONCLUSIONS: CYP isoform expression rates and glutathione system were greatly violated with MS. The greater changes were observed in pubertal rats with MS. PMID- 27371823 TI - Tissue injury and repair following cutaneous exposure of mice to sulfur mustard. AB - In mouse skin, sulfur mustard (SM) is a potent vesicant, damaging both the epidermis and the dermis. The extent of wounding is dependent on the dose of SM and the duration of exposure. Initial responses include erythema, pruritus, edema, and xerosis; this is followed by an accumulation of inflammatory leukocytes in the tissue, activation of mast cells, and the release of mediators, including proinflammatory cytokines and bioactive lipids. These proinflammatory mediators contribute to damaging the epidermis, hair follicles, and sebaceous glands and to disruption of the epidermal basement membrane. This can lead to separation of the epidermis from the dermis, resulting in a blister, which ruptures, leading to the formation of an eschar. The eschar stimulates the formation of a neoepidermis and wound repair and may result in persistent epidermal hyperplasia. Epidermal damage and repair is associated with upregulation of enzymes generating proinflammatory and pro-growth/pro-wound healing mediators, including cyclooxygenase-2, which generates prostanoids, inducible nitric oxide synthase, which generates nitric oxide, fibroblast growth factor receptor 2, and galectin-3. Characterization of the mediators regulating structural changes in the skin during SM-induced tissue damage and wound healing will aid in the development of therapeutic modalities to mitigate toxicity and stimulate tissue repair processes. PMID- 27371824 TI - A convenient purification method for silver nanoclusters and its applications in fluorescent pH sensors for bacterial monitoring. AB - Herein, we report a convenient approach to purify water-soluble dihydrolipoic acid (DHLA)-capped Ag nanoclusters (Ag NCs) by pH-induced precipitation under acidic conditions. The fluorescence of Ag NCs could be completely recovered by re dispersing the precipitate into a basic solution using DHLA and NaBH4 as stabilizing ligands and etching reagent. DHLA-Ag NCs-doped agarose hydrogels have been prepared to monitor pH with a wide range from 8.0 to 4.0. When pH decreased, the fluorescence of the hydrogels under a UV lamp decreased and completely disappeared after pH 5. The DHLA-Ag NCs-doped agarose hydrogels biosensor showed low cytotoxicity and long stability. Accordingly, a fluorescent pH sensor for bacterial monitoring has been employed based on the "OFF-ON" signal switch of the Ag NCs-agarose hydrogel. PMID- 27371825 TI - Live cell monitoring of glycine betaine by FRET-based genetically encoded nanosensor. AB - Glycine betaine (GB) is one of the key compatible solutes that accumulate in the cell at exceedingly high level under the conditions of high salinity. It plays a crucial role in the maintenance of osmolarity of the cell without affecting the physiological processes. Analysis of stress-induced physiological conditions in living cells, therefore, requires real-time monitoring of cellular GB level. Glycine Betaine Optical Sensor (GBOS), a genetically-encoded FRET-based nanosensor developed in this study, allows the real-time monitoring of GB levels inside living cells. This nanosensor has been developed by sandwiching GB binding protein (ProX) between the Forster resonance energy transfer (FRET) pair, the cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP). Conformational change in ProX, which was used as sensory domain, reported the change in the level of this compatible solute in in vitro and in vivo conditions. Binding of the GB to the sensory domain fetches close to both the fluorescent moieties that result in the form of increased FRET ratio. So, any change in the concentration of GB is correlated with change in FRET ratio. This sensor also reported the GB cellular dynamics in real-time in Escherichia coli cells after the addition of its precursor, choline. The GBOS was also expressed in yeast and mammalian cells to monitor the intracellular GB. Therefore, the GBOS represents a unique FRET-based nanosensor which allows the non-invasive ratiometric analysis of the GB in living cells. PMID- 27371826 TI - A Continuous Solution to the Norming Problem. AB - Conventional methods for producing test norms are often plagued with "jumps" or "gaps" (i.e., discontinuities) in norm tables and low confidence for assessing extreme scores. We propose a new approach for producing continuous test norms to address these problems that also has the added advantage of not requiring assumptions about the distribution of the raw data: Norm values are established from raw data by modeling the latter ones as a function of both percentile scores and an explanatory variable (e.g., age). The proposed method appears to minimize bias arising from sampling and measurement error, while handling marked deviations from normality-such as are commonplace in clinical samples. In addition to step-by-step instructions in how to apply this method, we demonstrate its advantages over conventional discrete norming procedures using norming data from two different psychometric tests, employing either age norms ( N = 3,555) or grade norms ( N = 1,400). PMID- 27371827 TI - Dopamine and opioid systems interact within the nucleus accumbens to maintain monogamous pair bonds. AB - Prairie vole breeder pairs form monogamous pair bonds, which are maintained through the expression of selective aggression toward novel conspecifics. Here, we utilize behavioral and anatomical techniques to extend the current understanding of neural mechanisms that mediate pair bond maintenance. For both sexes, we show that pair bonding up-regulates mRNA expression for genes encoding D1-like dopamine (DA) receptors and dynorphin as well as enhances stimulated DA release within the nucleus accumbens (NAc). We next show that D1-like receptor regulation of selective aggression is mediated through downstream activation of kappa-opioid receptors (KORs) and that activation of these receptors mediates social avoidance. Finally, we also identified sex-specific alterations in KOR binding density within the NAc shell of paired males and demonstrate that this alteration contributes to the neuroprotective effect of pair bonding against drug reward. Together, these findings suggest motivational and valence processing systems interact to mediate the maintenance of social bonds. PMID- 27371828 TI - N(6)-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression. AB - The internal N(6)-methyladenosine (m(6)A) methylation of eukaryotic nuclear RNA controls post-transcriptional gene expression, which is regulated by methyltransferases (writers), demethylases (erasers), and m(6)A-binding proteins (readers) in cells. The YTH domain family proteins (YTHDF1-3) bind to m(6)A modified cellular RNAs and affect RNA metabolism and processing. Here, we show that YTHDF1-3 proteins recognize m(6)A-modified HIV-1 RNA and inhibit HIV-1 infection in cell lines and primary CD4(+) T-cells. We further mapped the YTHDF1 3 binding sites in HIV-1 RNA from infected cells. We found that the overexpression of YTHDF proteins in cells inhibited HIV-1 infection mainly by decreasing HIV-1 reverse transcription, while knockdown of YTHDF1-3 in cells had the opposite effects. Moreover, silencing the m(6)A writers decreased HIV-1 Gag protein expression in virus-producing cells, while silencing the m(6)A erasers increased Gag expression. Our findings suggest an important role of m(6)A modification of HIV-1 RNA in viral infection and HIV-1 protein synthesis. PMID- 27371830 TI - Sustainability of Community-Based Youth Smoking Cessation Programs: Results From a 3-Year Follow-Up. AB - A national survey of 591 community-based youth smoking cessation programs provided an opportunity to assess the sustainability of health promotion programming over a 3-year period. Initial survey questions were mapped to five sustainability domains (local ownership, organizational alignment, resources, demand, and standard operating procedures) and examined to identify correlates of sustained operation. Follow-up surveys were completed with 305 programs. Assuming loss to follow-up indicated failure to sustain, the overall rate of program continuation was 32%. Baseline correlates of sustaining operation included the following: serving more youth, training staff in smoking cessation, longer time in operation at the initial survey, and receiving state funding as a sole source of support. Primary reasons for discontinuation related to lack of funding, insufficient enrollment, change of focus from tobacco cessation, and scheduling difficulty. Replication of studies like this survey of youth smoking cessation programs with other types of health promotion and public health programming can further test sustainability frameworks, provide validated measures, and ultimately inform a robust and replicable array of lasting, effective, evidence based public health programs. PMID- 27371829 TI - 53BP1 and USP28 mediate p53-dependent cell cycle arrest in response to centrosome loss and prolonged mitosis. AB - Mitosis occurs efficiently, but when it is disturbed or delayed, p53-dependent cell death or senescence is often triggered after mitotic exit. To characterize this process, we conducted CRISPR-mediated loss-of-function screens using a cell based assay in which mitosis is consistently disturbed by centrosome loss. We identified 53BP1 and USP28 as essential components acting upstream of p53, evoking p21-dependent cell cycle arrest in response not only to centrosome loss, but also to other distinct defects causing prolonged mitosis. Intriguingly, 53BP1 mediates p53 activation independently of its DNA repair activity, but requiring its interacting protein USP28 that can directly deubiquitinate p53 in vitro and ectopically stabilize p53 in vivo. Moreover, 53BP1 can transduce prolonged mitosis to cell cycle arrest independently of the spindle assembly checkpoint (SAC), suggesting that while SAC protects mitotic accuracy by slowing down mitosis, 53BP1 and USP28 function in parallel to select against disturbed or delayed mitosis, promoting mitotic efficiency. PMID- 27371831 TI - Corrigendum to 'Hybrid two-stage repair of thoracoabdominal aortic aneurysm'[Multimedia Man Cardiothoracic Surg 13 May 2016]. PMID- 27371832 TI - Do Health Systems Have Consistent Performance Across Locations and Is Consistency Associated With Higher Performance? AB - This study addresses whether health systems have consistent diabetes care performance across their ambulatory clinics and whether increasing consistency is associated with improvements in clinic performance. Study data included 2007 to 2013 diabetes care intermediate outcome measures for 661 ambulatory clinics in Minnesota and bordering states. Health systems provided more consistent performance, as measured by the standard deviation of performance for clinics in a system, relative to propensity score-matched proxy systems created for comparison purposes. No evidence was found that improvements in consistency were associated with higher clinic performance. The combination of high performance and consistent care is likely to enhance a health system's brand reputation, allowing it to better mitigate the financial risks of consumers seeking care outside the organization. These results suggest that larger health systems are most likely to deliver the combination of consistent and high-performance care. Future research should explore the mechanisms that drive consistent care within health systems. PMID- 27371834 TI - [Intraperitoneal transplantation of acellular extracellular matrix-derived biomaterial has no response to innate immunity in mice]. AB - Objective To explore the effect of acellular extracellular matrix (ECM) transplantation on the innate immunity (including macrophages and neutrophils) of mice, and establish a method evaluating the immunogenicity of acellular ECM material in mice as experimental animals. Methods Fresh membrane material and newly-processed acellular ECM material without DNA were separately intraperitoneally transplanted into mice. Seven days later, samples were collected to measure spleen index. The absolute numbers of neutrophils in peripheral blood and macrophages in peritoneal fluid were determined by BD Trucount tubes. The concentrations of interleukin 2 (IL-2), IL-4, IL-6, interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), IL-17A and IL-10 in the plasma and peritoneal fluid were detected by BD(TM) Cytometric Bead Array (CBA) mouse Th1/Th2/Th17 cytokine kit. Results Compared with sham group, the body mass is not increased in the mice transplanted with fresh membrane material, but the spleen index increased. The fresh material could dramatically increase the numbers of neutrophils in peripheral blood and macrophages in peritoneal fluid, and increase IL-6 and IFN-gamma production. However, acellular ECM material prepared by improved technique only had minor or even no effect on those parameters. Conclusion Acellular ECM material with DNA removed has no obvious response to the inherent immunity in mice. PMID- 27371833 TI - The Evolutionary Fates of a Large Segmental Duplication in Mouse. AB - Gene duplication and loss are major sources of genetic polymorphism in populations, and are important forces shaping the evolution of genome content and organization. We have reconstructed the origin and history of a 127-kbp segmental duplication, R2d, in the house mouse (Mus musculus). R2d contains a single protein-coding gene, Cwc22 De novo assembly of both the ancestral (R2d1) and the derived (R2d2) copies reveals that they have been subject to nonallelic gene conversion events spanning tens of kilobases. R2d2 is also a hotspot for structural variation: its diploid copy number ranges from zero in the mouse reference genome to >80 in wild mice sampled from around the globe. Hemizygosity for high copy-number alleles of R2d2 is associated in cis with meiotic drive; suppression of meiotic crossovers; and copy-number instability, with a mutation rate in excess of 1 per 100 transmissions in some laboratory populations. Our results provide a striking example of allelic diversity generated by duplication and demonstrate the value of de novo assembly in a phylogenetic context for understanding the mutational processes affecting duplicate genes. PMID- 27371835 TI - [Secretory acid phosphatase of Mycobacterium tuberculosis inhibits the autophagy of murine macrophages]. AB - Objective To investigate the effect of secretory acid phosphatase as a virulence factor of Mycobacterium tuberculosis (SapM) on the autophagy of murine macrophages. Methods GFP-LC3-Raw264.7 cells were treated with SapM, wortmannin, or starvation. Then the formation of autophagosomes was observed under a fluorescence microscope. The level of microtubule-associated protein 1 light chain 3 (LC3) II was detected using Western blotting. After chloroquine was added in the SapM-treated cells, LC3II level was again tested by Western blotting. Results Both starvation and SapM increased the number of GFP-LC3 puncta and the level of LC3 II. There was no further increase of LC3 II level in SapM-treated cells after chloroquine addition. Conclusion SapM can block autophagosome lysosome fusion and inhibit autophagy of murine macrophages. PMID- 27371836 TI - [Lipid derivative of benzylidene malononitrile AG490 attenuates airway inflammation of mice with neutrophilic asthma]. AB - Objective To observe the effect of lipid derivative of benzylidene malononitrile AG490 on the airway inflammation in a mouse model of neutrophilic asthma (NA). Methods Fifty-four specific pathogen-free (SPF) female C57BL/6 mice were randomly divided into 3 groups: NA group, AG490-treated NA (NAAG) group, and normal control (NC) group, 18 mice in each group. The NA group and the NAAG group were sensitized by airway instillation of ovalbumin (OVA) and lipopolysaccharide (LPS) on day 0, 6 and 13. The NAAG group was injected with AG490 (500 MUg/mouse, i.p.) three times a week, from day 0 after the first sensitization, for 3 weeks. Mice were challenged on day 21, 22 for 1 hour/time with an aerosol of 10 g/L OVA. At 24 hours after the final challenge, bronchoalveolar lavage fluid (BALF) was collected. The total number and differential counts of nucleated cells and the percentage of each type were determined. HE staining and PAS staining was employed for observing the lung pathological changes. The percentages of Th17 cells and regulatory T cells (Treg) in the lung issue were determined by flow cytometry. The level of interleukin-17 (IL-17) in BALF was measured using ELISA. Results Compared with the NA group, the total number of nucleated cells, the percentage of neutrophils and the percentage of eosinophils in BALF in the NAAG group were obviously reduced; lung tissue pathologic changes were improved in the NAAG group; goblet cell hyperplasia and the level of IL-17 in BALF in the NAAG group were significantly down-regulated; the proportion of Treg in the lung increased and the proportion of Th17 cells in the lung decreased in the NAAG group. Conclusion After NA mice are treated with AG490 during the sensitization phase, the proportion of Treg in the lung would increase and the proportion of Th17 cells in the lung would decrease. AG490 could attenuate the airway inflammation in the mouse model of NA. PMID- 27371837 TI - [The preventive effect of total saponins of Panax japonicus on nonsteroidal anti inflammatory drug-induced enteropathy]. AB - Objective To investigate the preventive effect of total saponins of Panax japonicus (SPJ) on nonsteroidal anti-inflammatory drug (NSAID)-induced intestinal injuries in mice. Methods NSAID-induced intestinal mucosal damaged models were established by intragastric administration of 5 mg/mL diclofenac sodium in mice for continuous 2 days. Since 4 days before the modeling, the mice in the experimental group were given SPJ once a day for 6 days. The small intestinal mucosal permeability was detected by fluorescein isothiocyanate-dextran (FITC-DT) and Evans blue staining. The small intestinal mucosal lesions were observed by HE staining; immunofluorescence staining was used to determine the expressions of endoplasmic reticulum stress response protein glucose transporter protein 78 (GRP78) and tumor necrosis factor alpha (TNF-alpha) in the intestinal mucosal epithelial cells. Results In the model group, small intestinal mucosal injury was serious. Evans blue staining and FITC-DT labeling showed the blue spots were denser and mucosal permeability increased significantly in the model group. HE staining revealed the intestinal mucosal villus degeneration, necrosis, shedding, and inflammatory cell infiltration in the model group, which meant the intestinal mucosal damage models were successfully established. And different concentrations of SPJ protected intestinal mucosa, meanwhile the expressions of GRP78 and TNF- alpha were significantly reduced in the intestinal epithelial cells as indicated by immunofluorescence staining. Conclusion There is a certain preventive effect of total SPJ on NSAID-induced intestinal injuries via the endoplasmic reticulum stress pathway. PMID- 27371838 TI - [Phospholipase C delta1 (PLCD1) inhibits the proliferation, invasion and migration of CAPAN-1 and BXPC-3 pancreatic cancer cells]. AB - Objective To explore the effect of phospholipase C delta1 (PLCD1) transfection on the biological behaviors of pancreatic cancer cells. Methods HPDE6C7 normal human pancreatic ductal epithelial cells and CAPAN-1, PANC-1, ASPC-1 and BXPC-3 pancreatic cancer cells were cultured. Reverse transcription PCR was used to screen the pancreatic cancer cells with low expression level of PLCD1. Recombinant plasmid pcDNA3.1-PLCD1 transfected pancreatic cancer cells CAPAN-1 and BXPC-3 with low expression level of PLCD1, and meanwhile the corresponding vector pcDNA3.1 transfection group was set up. The expression level of PLCD1 mRNA was detected by reverse transcription PCR, and the protein level was examined by Western blotting in pancreatic cancer cells CAPAN-1 and BXPC-3 after transfection. After the expression of PLCD1 was upregulalted in CAPAN-1 and BXPC 3 pancreatic cancer cells, the cell proliferation was analyzed by CCK-8 assay; flow cytometry was used to test the cell cycle and apoptosis; Transwell(TM) assay was performed to evaluate the invasion and migration ability of the cells. Results The study obtained CAPAN-1 and BXPC-3 cells with lower expression of PLCD1. The expression levels of PLCD1 mRNA and protein obviously increased in CAPAN-1 and BXPC-3 cells after transfected with plasmid pcDNA3.1-PLCD1, and the abilities of cell proliferation, invasion and migration were restrained. The cell cycle was arrested in G0/G1 phase, and cell apoptosis was remarkably promoted. Conclusion PLCD1 transfection can induce the apoptosis of CAPAN-1 and BXPC-3 cells, arrest the cell cycle in G0 /G1 phase. Meanwhile, it inhibits the abilities of cell proliferation, invasion and migration of CAPAN-1 and BXPC-3 cells. PMID- 27371839 TI - [Eukaryotic expression and application of HCV Hebei strain E2 extracellular core region]. AB - Objective To express core region of HCV1b (Hebei strain) E2 protein (E2c) by eukaryotic system, and establish the detection method of specific anti-HCV E2 antibody in the sera from hepatitis C patients. Methods Based on the literature, the E2c gene was modified from the HCV1b gene and synthesized via overlapping PCR. Thereafter, the E2c gene including tissue-type plasminogen activator (tPA) signal peptide was cloned into the pCI-neo eukaryotic expression vector, and the product was named pCI-tpa-1bE2c. After HEK293T cells were transfected with pCI tpa-1bE2c, the supernatant was collected, condensed and purified. Its specificity was identified by Western blotting. Galanthus nivalis agglutinin (GNA)-based ELISA was used to detect the antibody against HCVE2 in the sera from hepatitis C patients. Results Modified HCV E2c protein was successfully expressed in HEK293T cells and the GNA-based ELISA was developed for detecting the antibody against HCV E2 in the sera from hepatitis C patients. Conclusion HCV-1bE2c protein can be effectively expressed in HEK293T cells and applied clinically. PMID- 27371840 TI - [beta-catenin is involved in BMP9-induced differentiation of C3H10T1/2 cells into cardiomyocyte-like cells]. AB - Objective To investigate the role of beta-catenin in the differentiation of C3H10T1/2 cells into cardiomyocyte-like cells induced by bone morphogenetic protein 9 (BMP9). Methods C3H10T1/2 cells were transfected with the recombinant adenovirus expressing BMP9 (Ad-BMP9) and differentiated into cardiomyocytes in vitro for up to 21 days. The activated level of beta-catenin in the cells after cultivated with Ad-BMP9 and different concentrations of beta-catenin specific inhibitor XAV-939 was detected by Western blotting. Real-time quantitative PCR (qRT-PCR) was performed to evaluate the expressions of cardiac specific gene myocyte enhancer factor 2C (MEF2C) and GATA binding protein 4 (GATA4) in the cells one week after induced by Ad-BMP9 and different concentrations of XAV-939. Three weeks after the transfection, the expressions of connexin 43 (Cx43) and cardiac troponin T (cTnT) were analyzed by Western blotting, and the location of Cx43 in the cells was observed by immunofluorescence technique. Results While the transfection was successful in 50% of the cells positive for BMP9, beta-catenin was excessively activated and their phosphorylation level remarkably increased. After XAV-939 inhibited the activity of beta-catenin, the expressions of MEF2C, GATA4, Cx43, cTnT in C3H10T1/2 cells induced by BMP9 were significantly suppressed. Conclusion The beta-catenin can be activated by BMP9 and the activation of beta-catenin plays an important role in the differentiation of C3H10T1/2 cells into cardiomyocyte-like cells induced by BMP9. PMID- 27371841 TI - [Tripartite motif-containing protein 34 (TRIM34) colocalized with micronuclei chromosome and hampers its movement to equatorial plate during the metaphase stage of mitosis]. AB - Objective To examine whether tripartite motif-containing protein 34 (TRIM34) is colocalized with micronuclei and investigate the influence on the movement of micronuclei chromosome in mitosis. Methods The eukaryotic expression vector TRIM34-pEGFP-N3 was constructed, identified and then transfected into HEK293T cells. With 4', 6-diamidino-2-phenylindole 2HCI (DAPI) staining, the colocalization between TRIM34 and micronuclei was observed under a fluorescence microscope. Moreover, MitoTracker(R)Deep Red was used to identify the colocalization between the complex of TRIM34-micronulei and mitochondria under a confocal microscope. Finally, the effect of TRIM34 on the movement of micronuclei chromosome in mitosis was examined. Results DNA sequencing confirmed that the vector TRIM34-pEGFP-N3 was constructed successfully. A fluorescence microscope revealed that TRIM34 could be colocalized with micronuclei in HEK293T cells transfected with TRIM34-pEGFP-N3. In the same manner, a confocal microscope distinctly showed that TRIM34 was colocalized with micronuclei similarly in appearance. However, there was no distinguished colocalization relationship between the complex of TRIM34-micronulei and mitochondria. Interestingly, the micronuclei chromosome conjugated with TRIM34 was hardly transferred to equatorial plate during the metaphase stage of mitosis. Conclusion TRIM34 is colocalized with micronuclei chromosome and hampers its movement to equatorial plate in mitosis. PMID- 27371842 TI - [The establishment of 5637 bladder cancer cell line with stable overexpression of miR-449c]. AB - Objective To establish a human bladder cancer cell line that stably overexpresses miR-449c. Methods The DNA fragments encoding pre-miR-449c were amplified from genomic DNA templates of HEK293 cells using high-fidelity PCR and cloned into FtetUGW-T vector. The recombinant plasmid was verified by sequencing and applied for lentivirus packaging. Human bladder cancer 5637 cells were infected with the lentivirus and the infected cells after selection with puromycin were observed using an inverted fluorescent microscope for enhanced green fluorescent protein (EGFP) expression, real-time quantitative PCR for miR-449c expression and Western blotting for the expression of its downstream target C-myc. Results The FtetUGW T/miR-449C lentivirus was successfully established. The human 5637 bladder cancer cells infected with the lentivirus expressed EGFP and overexpressed miR-449c. The expression of c-myc in the cells that stably overexpressed miR-449c was significantly reduced compared with control cells. Conclusion 5637 bladder cancer cell line that stably overexpresses miR-449c is successfully established. PMID- 27371843 TI - [Overexpression of SEPP1 inhibits the proliferation and induces cell cycle G2/M arrest of 786-O and 769-P human renal carcinoma cells]. AB - Objective To establish selenoprotein P, plasma 1 (SEPP1) gene recombinant lentiviral vector and investigate the effect of SEPP1 on the proliferation of human clear cell renal cell carcinoma (ccRCC) cells. Methods cDNA sequence of SEPP1 was cloned from the total cDNA of HEK293T cells by PCR. Then, the cDNA fragment was combined with the pLV-EGFP(2A)Puro vector and the constructed plasmid pLV-EGFP(2A)Puro-SEPP1 was transfected into HEK293T cells for packaging the virus. Forty-eight hours after transfected with the virus supernatant, the level of SEPP1 protein in 769-P and 786-O cells were tested by Western blotting. Cells were divided into recombinant lentivirus-infected cells, empty vector lentivirus-infected cells and the blank control cells. Cell proliferation rate was detected by MTS assay, colony forming ability was evaluated by plate clony formation assay and cell cycle change was assayed by flow cytometry after transfected with pLV-EGFP(2A)Puro-SEPP1 or empty pLV-EGFP(2A)Puro vector. Results Enzyme digestion analysis and DNA sequencing showed that the recombinant plasmid pLV-EGFP(2A)Puro-SEPP1 was constructed successfully. After being infected by the virus supernatant, the 786-O and 769-P cells expressed EGFP. Compared with the empty vector group and the blank control group, expression level of SEPP1 in the experimental group was much higher. The cell proliferative ability was inhibited in the cells overexpressing SEPP1, and the colony forming ability of SEPP1 overexpressed cells evidently decreased. Cell cycle was arrested in G2/M phase in 786-O cells overexpressing SEPP1. Conclusion The recombinant plasmid pLV EGFP(2A)Puro-SEPP1 has been constructed successfully. Overexpression of SEPP1 could significantly reduce the proliferation rate of 786-O and 769P cells, and cause G2/M phase arrest of 786-O cells. PMID- 27371844 TI - [Qiyusanlong decoction inhibits the level of PD-1/PD-L1 in mice bearing Lewis lung carcinoma]. AB - Objective To investigate the anti-tumor effect of Qiyusanlong decoction (QYSL) in the mice with Lewis lung cancer (LLC) and its effect on the expression of programmed death 1 and programmed death ligand 1 (PD-1/PD-L1). Methods The model of lung cancer subcutaneous allograft was established using LLC cells. The model mice were randomly divided into six groups: a model group, a chemotherapy group, three QYSL groups of high, middle and low doses, and a combined group, each group containing 8 mice. On the 11th day, the low-, middle- and high-dose QYSL groups were respectively given intragastric administration of 20.12, 40.24, 80.48 g/(kg.d) QYSL; the chemotherapy group were intraperitoneally injected with 0.4 mL cisplatin; the combined group were administrated with cisplatin and high-dose QYSL; the model group were administrated with the same amount of normal saline, once a day for 10 days. Tumor volume was examined and tumor growth curve was drawn. Tumors were weighed and tumor inhibition rates were calculated. The expressions of PD-1, PD-L1 mRNA and protein in spleens and tumor tissues of mice were detected by real-time quantitative PCR and Western blotting, respectively. Results Compared with the model group, the high-dose QYSL group could inhibit tumor growth with tumor inhibition rate being 23.86%; the tumor inhibition rate between the combined group and the chemotherapy group was equal. The high-dose QYSL could significantly decrease the expression of PD-1 mRNA and protein in spleen and inhibited the expression of PD-L1 mRNA and protein in tumor. The levels of PD-1 and PD-L1 protein in the combined group were obviously lower than those in the chemotherapy group, but the interaction effect of the other indicators had no statistical significance. Conclusion QYSL can moderately inhibit the growth of the transplanted tumor by decreasing PD-1/PD-L1 level. PMID- 27371845 TI - [Dynamic changes of circulating monocyte subsets in high-NaCl diet fed mice]. AB - Objective To observe the dynamic changes of the circulating monocyte subsets in C57BL/6 mice fed with high-NaCl diet. Methods Male C57BL/6 mice were randomly divided into three groups: 9, 40 and 80 g/L NaCl groups. Before the treatment and 4, 8 and 12 weeks after the treatment, the cardiac function was dynamically determined by echocardiography and the blood pressure was measured by tail-cuff plethysmography. Flow cytometry analysis of circulating monocyte subsets was performed. HE staining was used to observe cardiac pathological changes at the time of sacrifice. Results Systolic blood pressure significantly increased with the progression of the high-salt diet. Compared with 9 g/L NaCl group, the ejection fraction of the other two groups slightly increased at week 4, followed by a significant decreasing trend up to week 12, in addition, the percentage of Ly6C(high) monocyte subset showed a progressive increase during high-salt feeding and reached a plateau at week 4, and then abruptly went down up to week 12. On the contrary, Ly6C(low) monocyte subset had an opposite trend, whereas Ly6C(int) monocyte subset remained constant. HE staining showed that cardiomyocyte size, as determined by the myocyte cross-sectional area, became enlarged obviously in the latter two groups. Conclusion Circulating monocyte subsets dynamically changed in the mice fed with high-salt diet. PMID- 27371846 TI - [Lily polysaccharide 1 enhances the effect of metformin on proliferation and apoptosis of human breast carcinoma cells]. AB - Objective To investigate the effect of metformin, alone or in combination with Lily polysaccharide 1 (LP1), on cell viability and apoptosis in MCF-7 human breast cancer cells. Methods LP1 (0.5, 1.0 mg/mL) and metformin (5, 10, 20, 50 mmol/L) were added into MCF-7 cell culture medium, followed by incubating for 72 hours in carbon dioxide incubators at 37DegreesCelsius. MCF-7 cell proliferation was determined using MTT assay; the apoptosis and cell cycle of MCF-7 cells were examined using annexin V-FITC/PI double staining combined with flow cytometry; Western blotting was used to determine the content of Bcl-2, Bax, adenosine monophosphate-activated protein kinase (AMPK) and phosphorated AMPK (p-AMPK) proteins. Results Metformin-induced inhibition of MCF-7 cell proliferation was significantly enhanced when 1 mg/mL LP1 was added in. Compared with the control group and the metformin only group, more cells were arrested to G1 and the apoptosis rate was raised obviously in the metformin and LP1 combination group. LP1 promoted the downregulated expression of Bcl-2 and the upregulated expression of Bax induced by metformin, but it didn't show any impact on the metformin activated AMPK pathway. Conclusion LP1 enhances the proliferation-inhibitory and apoptosis-promoting effect of metformin on human breast carcinoma cells. The mechanism may be related with Bcl-2 downregulation and Bax upregulation. PMID- 27371847 TI - [Astaxanthin inhibits proliferation and promotes apoptosis of A549 lung cancer cells via blocking JAK1/STAT3 pathway]. AB - Objective To investigate the anti-tumor effects of astaxanthin on A549 lung cancer cells and the related mechanisms. Methods A549 cells were cultured with various concentrations of astaxanthin (20, 40, 60, 80, 100 MUmol/L), and DMSO at the same concentrations served as vehicle controls. The viability of A549 cells was detected by CCK-8 assay; cell cycle and apoptosis were observed by flow cytometry; and the expressions of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), signal transducers and activators of transcription 3 (STAT3), and Janus kinase 1 (JAK1) were evaluated by Western blotting. Results CCK-8 assay showed that astaxanthin decreased the proliferation of A549 cells in a dose dependent manner. Flow cytometry showed that astaxanthin increased the number of cells in the G0/G1 phase and induced apoptosis in A549 cells. Western blotting showed that astaxanthin up-regulated the expression of Bax and down-regulated the expressions of Bcl-2, STAT3 and JAK1. Conclusion Astaxanthin functions as a potent inhibitor of A549 lung cancer cell growth by targeting JAK1/STAT3 signaling pathway. PMID- 27371848 TI - [Knockdown of STAT3 reduces the level of survivin and promotes the apoptosis of U87MG glioma cells]. AB - Objective To investigate the effect of signal transducer and activator of transcription (STAT3)-specific siRNA (siSTAT3) on the apoptosis of U87MG human glioma cells and its mechanism. Methods U87MG glioma cells were cultured in vitro. The effect of siSTAT3 on U87MG human glioma cells was evaluated by MTT assay to observe cell proliferation and by flow cytometry and acridine orange staining to observe cell apoptosis. Reverse transcription PCR and Western blotting were used to detect the expression of survivin. Results Compared with mock and si-scrambled groups, siSTAT3 expression plasmid inhibited the proliferation of U87MG cells obviously. Flow cytometry and acridine orange staining showed that siSTAT3 plasmid significantly promoted glioma cell apoptosis. In addition, siSTAT3 plasmid significantly inhibited the mRNA and protein levels of survivin. Conclusion Knockdown of STAT3 in U87MG cells can downregulate the level of survivin and remarkably promote the apoptosis of glioma cells. PMID- 27371849 TI - [Expression and clinical significance of IL-33 in patients with non-small cell lung cancer]. AB - Objective To investigate the expression of interleukin 33 (IL-33) in cancer and adjacent non-cancerous tissues from patients with non-small cell lung cancer (NSCLC). Methods Real-time quantitative PCR was performed to detect the mRNA expression of IL-33 in 61 pairs of cancerous and adjacent non-cancerous tissues. In addition, immunohistochemistry was used to evaluate the expression and location of IL-33 on paraffin sections in selected 12 cases with different pathological types, to analyze the correlation of IL-33 expression with clinicopathological variables and overall survival. Results The expression of IL 33 mRNA in cancer tissues was significantly lower than that in adjacent non cancerous tissues. The immunohistochemical results showed that IL-33 protein was mainly localized in the nucleus, and was obviously down-regulated in NSCLC. Besides, the expression of IL-33 was associated with histological type, but was not associated with age, gender, smoking history, differentiation status and pathological TNM stage. According to the Kaplan-Meier analysis, the expression of IL-33 mRNA was evidently associated with post-operative overall survival of patients suffering from NSCLC. Conclusion IL-33 may play an important role in the development of NSCLC and the targeted therapy. PMID- 27371850 TI - [The enhanced expression of Toll-like receptor 2 in CD8(+)T cells of chronic HBV infected patients]. AB - Objective To detect the level of Toll-like receptor 2 (TLR2) in CD8(+)T cells of chronic HBV infected patients without antiviral treatment. Methods Forty chronic HBV infected donors without antivirus treatment and 19 healthy donors were enrolled in our study. All donors were divided into three groups: a high viral load (HBV DNA>1*10(4) copies/mL) group, a low viral load (HBV DNA>1*10(4) copies/mL) group, and a healthy control group. After the isolation and staining of peripheral blood mononuclear cells (PBMCs), the levels of TLR2, CD38, HLA-DR, CD95, programmed death-1 (PD-1) in CD8(+)T cells were detected by flow cytometry to further analyze the correlations between TLR2 and CD38, HLA-DR, CD95, PD-1. Results The expression of TLR2 in CD8(+)T cells of the HBV infected patients were significantly higher than that in the healthy donors. The expression of TLR2 in CD8(+)T cells of the low viral load group was significantly higher than that in the high viral load group. There were no correlations between the expression of TLR2 and the expressions of CD38, HLA-DR, CD95 and PD-1 in CD8(+)T cells in the chronic HBV infected patients. Conclusion The expression of TLR2 in CD8(+)T cells increases in chronic HBV infected patients. PMID- 27371852 TI - [Silencing of ezrin gene inhibits proliferation and invasion of human prostate cancer PC-3 cells]. AB - Objective To observe the expression of ezrin in prostate cancer tissues and explore the effect of ezrin gene silencing on the proliferation and invasion of human prostate cancer PC-3 cells and involved mechanisms. Methods The paraffin embedded specimens of prostate cancer (n=20) and benign prostatic hyperplasia (n=20) were collected. Real-time quantitative PCR and Western blotting were used to detect the expression of ezrin mRNA and protein in prostate tissues, respectively. After culturing, human prostate cancer PC-3 cells were treated with culture solution, Scramble siRNA and ezrin siRNA for 48 hours. Cell proliferation was analyzed through MTT method. Cell invasion ability was measured using Transwell(TM) invasion experiment. In addition, the levels of E-cadherin and N cadherin were examined by real-time quantitative PCR and Western blotting. Results The expression levels of ezrin mRNA and protein in prostate cancer tissues were higher than those in the tissues from benign prostatic hyperplasia patients. In comparison with PC-3 cells treated with Scramble siRNA, following the downregulation of ezrin expression, PC-3 cell proliferation was significantly inhibited and mean cell number of penetrated membrane and N-cadherin level were reduced, whereas E-cadherin level was raised. There was no statistical difference in the above indicators between Scramble siRNA-treated PC-3 cells and pure culture solution-treated PC-3 cells. Conclusion Ezrin is highly expressed in prostate cancer tissues. Gene silence of ezrin inhibits the proliferation and invasion of human prostate cancer PC-3 cells, meanwhile the level of E-cadherin is upregulated and N-cadherin is downregulated. PMID- 27371851 TI - [Ag85B and BCG enhance immune activity of dendritic cells in patients with initially treated tuberculosis]. AB - Objective To investigate the regulatory effects of Mycobacterium tuberculosis major secreted protein Ag85B and Bacillus Calmette-Guerin (BCG) on the immune function of dendritic cells (DCs) in the patients with tuberculosis who have received an initial treatment. Methods The peripheral blood mononuclear cells were collected and separated in 26 healthy subjects and 31 patients with tuberculosis who had been treated initially. Every specimen was divided into 4 groups and DCs were induced and cultured. On the 6th day, the DCs in the three experimental groups were treated by lipopolysaccharide (LPS), BCG, Ag85B, respectively and no-treated DCs served as a control group. After 24-hour treatment, DCs were collected and examined for the levels of CD83, CD86, HLA-DR and CD11c using flow cytometry. Moreover, the levels of interleukin 12 (IL-12), IL-10 and interferon gamma (IFN-gamma) in the supernatants were measured by ELISA. Results The expression levels of CD83 and IL-10 in the patient control group were significantly lower than those in healthy subject control group. The levels of CD83, CD86 and IFN-gamma in the Ag85B treated group were obviously high than those in the control group. The level of IFN-gamma in the BCG treated group was significantly high than that in the control group. The levels of CD83, CD86, HLA-DR and IL-10 in the LPS treated group were remarkably higher than those in the control group. The levels of CD83, CD86 and IL-10 in the healthy subject LPS treated group were significantly higher than those in the healthy subject control group. Conclusion The immune-enhancing effect of Ag85B on DCs is superior to that of BCG in the patients with initially treated tuberculosis. PMID- 27371853 TI - [Construction and panning of scFv phage display library against recombinant interleukin 4 receptor]. AB - Objective To construct the recombinant human interleukin 4 receptor (rhIL-4R) single-chain Fv (scFv) antibody library by phage display technique to obtain the anti-IL-4R scFv clones selected from the library. Methods Total RNA was extracted from splenocytes of the BALB/c mice immunized with rhIL-4R. Complementary DNA fragments of variable heavy (VH) and variable light (VL) chains of the antibodies were prepared by reverse transcription PCR and assembled into scFv by splice overlap extension PCR (SOE-PCR). Both scFv and the pCANTAB5E vector were respectively double-digested with restriction endonuclease Sfi I and Not I, connected with T4 ligase, and then transformed into the competent cells E.coli TG1; it was cultured in medium to obtain the phage scFv antibody library; after three rounds of enrichment and panning, the specific antigen scFv with high affinity was selected for the sequencing. Results After three rounds of panning, we obtained a diversity of approximately 2*10(8) anti-rhIL-4R scFv antibody library. Sequencing analysis of one positive clone showed that the anti-rhIL-4R scFv was 741 bp and coded 247 amino acids. The analysis of VBASE2 database indicated that VH and VL gene sequences of anti-rhIL-4R protein all had three complementarity determining regions and four backbone areas.Conclusion The anti rhIL-4R scFv was obtained from the scFv antibody library. PMID- 27371854 TI - Liquid Chromatographic Separation of Novel 4-Amino-Flavanes Series Diastereomers on a Polysaccharide-Type Chiral Stationary Phase. AB - Two broad approaches for the syntheses of a series of 4-aminoflavanes are used in this study, and they have been prepared in 30-99% overall yields using the reductive condensation of flavanone with primary amine, as a key step. By this methodology, the formyl derivatives of several secondary amines were obtained in good to excellent yields. The structures of all new products have been confirmed by spectral experiences (IR, 1H NMR and 13C NMR). However, the present non stereoselective synthesis results in a mixture of 2-7: diastereomers, which differ from the configuration of the flavanone atom asymmetric center. Since each diastereomer may have different biological activity and pharmacokinetic profile, analytical methods have to be developed for their separation. The 4-aminoflavanes diastereomers were separated using polysaccharide chiral stationary phases columns consisting of cellulose (Chiralcel(r) OD-H and Chiralcel(r)OJ) by high performance liquid chromatography; the separation was affected by the nature and concentration of the alcohol modifiers in the mobile phase. Separations were carried out under normal phase mode on the Chiralcel(r)OJ column. This method can properly separate the two diastereoisomers (Rs > 2) within an analysis time of <50 min. PMID- 27371855 TI - Chiral Capillary Electrophoresis-Mass Spectrometry: Developments and Applications in the Period 2010-2015: A Review. AB - The sensitive detection of chiral compounds by capillary electrophoresis (CE) in biological samples remains a significant challenge and is currently considered a bottleneck in many chiral analysis projects. Chiral CE-MS can significantly improve the limit of detection and provide high sensitivity compared with chiral CE-UV. Chiral selectors such as modified cyclodextrins (CDs) and polymeric surfactants (a.k.a. molecular micelles, MoMs) in electrokinetic chromatography (EKC), micellar electrokinetic chromatography (MEKC) and capillary electrochromatography (CEC) have been developed to address the need for high sensitivity by CE-MS. However, several problems remain to be investigated to fully understand the potential of these hyphenation modes. This review provides introduction to major chiral CE-MS modes for the novice and highlights the important working principles of each mode of chiral CE-MS. Next, recent practical developments and progress in chiral CE-MS dating from January 2010 to September 2015 are described. The achievements in clinical and biomedical sciences using a variety of chiral selectors such as CDs and MoMs in EKC-MS, MEKC-MS and CEC-MS are discussed. Finally, conclusions and future prospects of CE-MS in chiral analysis are drafted. PMID- 27371856 TI - Dissection of quantitative traits by bulk segregant mapping in a protoploid yeast species. AB - Since more than a decade ago, Saccharomyces cerevisiae has been used as a model to dissect complex traits, revealing the genetic basis of a large number of traits in fine detail. However, to have a more global view of the genetic architecture of traits across species, the examination of the molecular basis of phenotypes within non-conventional species would undoubtedly be valuable. In this respect, the Saccharomycotina yeasts represent ideal and potential non-model organisms. Here we sought to assess the feasibility of genetic mapping by bulk segregant analysis in the protoploid Lachancea kluyveri (formerly S. kluyveri) yeast species, a distantly related species to S. cerevisiae For this purpose, we designed a fluorescent mating-type marker, compatible with any mating-competent strains representative of this species, to rapidly create a large population of haploid segregants (>10(5) cells). Quantitative trait loci can be mapped by selecting and sequencing an enriched pool of progeny with extreme phenotypic values. As a test bed, we applied this strategy and mapped the causal loci underlying halotolerance phenotypes in L. kluyveri Overall, this study demonstrates that bulk segregant mapping is a powerful way for investigating the genetic basis of natural variations in non-model yeast organisms and more precisely in L. kluyveri. PMID- 27371857 TI - The birth of enthusiasm and passion for science. AB - In this paper I describe the main aspects of my career and focus on the retrospective on my life and my work. PMID- 27371858 TI - Morphology of mitochondrial nucleoids in respiratory-deficient yeast cells varies depending on the unit length of the mitochondrial DNA sequence. AB - We investigated the morphology of mitochondrial nucleoids (mt-nucleoids) and mitochondria in Saccharomyces cerevisiae rho(+) and rho(-) cells with DAPI staining and mitochondria-targeted GFP. Whereas the mt-nucleoids appeared as strings of beads in wild-type rho(+) cells at log phase, the mt-nucleoids in hypersuppressive rho(-) cells (HS40 rho(-) cells) appeared as distinct punctate structures. In order to elucidate whether the punctate mt-nucleoids are common to other rho(-) cells, we observed the mt-nucleoids in rho(-) strains that retain different unit lengths of the mitochondrial DNA (mtDNA) sequence. As a result, rho(-) cells that have long mtDNA sequences, of more than 30 kb, had mt-nucleoids with a strings-of-beads appearance in tubular mitochondria. In contrast, rho(-) cells that have short mtDNA sequences, of <1 kb, had punctate mt-nucleoids in tubular mitochondria. This indicates that the morphology of mt-nucleoids in rho( ) cells significantly varies depending on the unit length of their mtDNA sequence. Analyses of mt-nucleoids suggest that the punctate mt-nucleoids in HS40 rho(-) cells consist of concatemeric mtDNAs and oligomeric circular mtDNAs associated with Abf2p and other nucleoid proteins. PMID- 27371859 TI - Contributions of the Individual Differences Approach to Cognitive Aging. AB - OBJECTIVE: To review selected research in cognitive aging incorporating an individual differences approach. METHOD: Three contributions of the individual differences perspective in cognitive aging are illustrated with data from the Virginia Cognitive Aging Project. RESULTS: Research capitalizing on the variability among individuals has been used to: (a) improve sensitivity and validity of measurement of cognitive functioning, and evaluate possible age differences in the meaning of the measures; (b) investigate relations between age and individual cognitive measures in the context of other types of cognitive measures; and (c) examine the degree to which age-related influences on target measures are statistically independent of age-related influences on other cognitive measures. DISCUSSION: Although the primary focus of much of the research in cognitive aging has been on mean differences between people of different ages, people differ in many respects besides age. A fundamental assumption of the individual differences perspective is that at least some of those differences may be informative about the nature, and causes, of the relations between age and cognitive functioning. PMID- 27371860 TI - Deciding on Therapy: New Tools Factor In Cost of Care. PMID- 27371861 TI - Everolimus Effectively Treats Neuroendocrine Tumors of Gut and Lungs. PMID- 27371862 TI - High Glycemic Index Associated With Increased Lung Cancer Risk. PMID- 27371864 TI - Solutions To Reduce Racial Mistrust. PMID- 27371865 TI - Poly(2-ethyloxazoline) as matrix for highly active electrospun enzymes in organic solvents. AB - Nanofibers are advantageous carriers for biocatalysts, because they show lower diffusion limitations due to their high surface/volume ratio. Only a few samples are known where enzymes are directly spun into nanofibers, mostly because there are not many suited polymer carriers. In this study, poly(2-ethyloxazoline) (PEtOx) was explored regarding its usefulness to activate various enzymes in organic solvents by directly electrospinning them from aqueous solutions containing the polymer. It was found that the concentration of PEtOx in the spinning solution and also the swellability of the fibers play a great role in the activity of the enzymes in organic solvents. Using electrospun lipase B from Candida antarctica (CaLB) under optimized conditions revealed a higher carrier activity than the commercial Novozyme 435 with 10 times less immobilized protein. The electrospinning of PEtOx/CaLB fibers onto a stirrer is used to realize a biocatalytic stirrer for organic solvents. Biotechnol. Bioeng. 2017;114: 39-45. (c) 2016 Wiley Periodicals, Inc. PMID- 27371866 TI - Interatrial septal pacing to suppress atrial fibrillation in patients with dual chamber pacemakers: A meta-analysis of randomized, controlled trials. AB - BACKGROUND: Atrial fibrillation (AF) is of frequent occurrence in a population with bradycardia indicated for permanent dual chamber pacing. Whether selective site pacing at interatrial septum (IAS) could better prevent AF as compared with standard atrial pacing (AP) from right atrial appendage or high right atrium in these conditions remains in question. Its safety profile has yet to be elucidated. METHODS: Major web databases were searched up to February 2015 for controlled, randomized clinical trials on IAS versus conventional pacing. The primary end point was freedom from persistent/permanent AF. Secondary outcomes included device-recorded AF burden and frequency of AF episodes, lead-related complications, and major adverse events (MAEs). RESULTS: We identified 10 eligible studies incorporating a total of 1245 patients. Compared to conventional AP, IAS pacing conferred no additional benefit on the persistent/permanent AF free survival (hazard ratio 0.76, 95% confidence interval [CI] 0.48 to 1.22); it was associated with notably reduced device-detected AF burden (standard mean difference [SMD] -0.32, 95% CI -0.55 to -0.09) and AF frequency (SMD -0.54, 95% CI -0.83 to -0.24). The odds of lead-related complications (odds ratio [OR] 1.64, 95% CI 0.87 to 3.08) and combined rate of MAEs (OR 1.05, 95% CI 0.60 to 1.82) were similar between two groups. CONCLUSIONS: IAS pacing has no influence on the persistent/permanent AF progression and MAEs, although it appears to lower device detected AF burden and AF frequency, and may carry similar risks of lead-related complications as compared to standard AP. PMID- 27371867 TI - Subcortical correlates of auditory perceptual organization in humans. AB - To make sense of complex auditory scenes, the auditory system sequentially organizes auditory components into perceptual objects or streams. In the conventional view of this process, the cortex plays a major role in perceptual organization, and subcortical mechanisms merely provide the cortex with acoustical features. Here, we show that the neural activities of the brainstem are linked to perceptual organization, which alternates spontaneously for human listeners without any stimulus change. The stimulus used in the experiment was an unchanging sequence of repeated triplet tones, which can be interpreted as either one or two streams. Listeners were instructed to report the perceptual states whenever they experienced perceptual switching between one and two streams throughout the stimulus presentation. Simultaneously, we recorded event related potentials with scalp electrodes. We measured the frequency-following response (FFR), which is considered to originate from the brainstem. We also assessed thalamo-cortical activity through the middle-latency response (MLR). The results demonstrate that the FFR and MLR varied with the state of auditory stream perception. In addition, we found that the MLR change precedes the FFR change with perceptual switching from a one-stream to a two-stream percept. This suggests that there are top-down influences on brainstem activity from the thalamo-cortical pathway. These findings are consistent with the idea of a distributed, hierarchical neural network for perceptual organization and suggest that the network extends to the brainstem level. PMID- 27371868 TI - Correlation between word recognition score and intracochlear new bone and fibrous tissue after cochlear implantation in the human. AB - Cochlear implantation is an effective, established procedure for patients with profound deafness. Although implant electrodes have been considered as biocompatible prostheses, surgical insertion of the electrode induces various changes within the cochlea. Immediate changes include insertional trauma to the cochlea. Delayed changes include a tissue response consisting of inflammation, fibrosis and neo-osteogenesis induced by trauma and an immunologic reaction to a foreign body. The goal of this study was to evaluate the effect of these delayed changes on the word recognition scores achieved post-operatively. Seventeen temporal bones from patients who in life had undergone cochlear implantation were prepared for light microscopy. We digitally calculated the volume of fibrous tissue and new bone within the cochlea using Amira((r)) three-dimensional reconstruction software and assessed the correlations of various clinical and histologic factors. The postoperative CNC word score was positively correlated with total spiral ganglion cell count. Fibrous tissue and new bone were found within the cochlea of all seventeen specimens. The postoperative CNC word score was negatively correlated with the % volume of new bone within the scala tympani, scala media/vestibuli and the cochlea, but not with the % volume of fibrous tissue. The % volume of new bone in the scala media/vestibuli was positively correlated with the degree of intracochlear insertional trauma, especially trauma to the basilar membrane. Our results revealed that the % volume of new bone as well as residual total spiral ganglion cell count are important factors influencing post-implant hearing performance. New bone formation may be reduced by limiting insertional trauma and increasing the biocompatibility of the electrodes. PMID- 27371869 TI - Challenges in Determining Genotypes for Pharmacogenetics in Allogeneic Hematopoietic Cell Transplant Recipients. AB - As part of a pharmacogenetic study, paired blood and oral fluid samples were tested for the IL28B polymorphism (rs12979860) before and after hematopoietic cell transplantation (HCT) to evaluate changes in the genotype and investigate the utility of genotyping in oral fluid in HCT recipients. In 54 patients with leukemia >18 years of age, samples were collected approximately 7 days before HCT and 60 days after HCT. IL28B polymorphism testing was performed using real-time PCR with allele-specific probes. Twenty-four patients had the same genotype as their donors. In 30 patients, the genotype was different from that of the donor. In the oral fluid samples, 4 retained the recipient's genotype, and 18 had a genotype that matched that of the donor. In the remaining 8 patients, the results could not be characterized and appeared to be a combination of both, suggesting mixed proportions of donor and recipient cells. The assumption was that the sloughed epithelial cells of the mouth are of recipient origin. However, oral fluid is a mixture that contains varying numbers of cells of the recipient and immunomodulatory cells from the donor. Therefore, the use of oral fluid after HCT for clinical pharmacogenetics purposes needs further investigation. PMID- 27371870 TI - Fabrication and characterization of poly(vinyl alcohol)-TiO2 nanocomposite films for orthopedic applications. AB - Poly(vinyl alcohol) (PVA) is reinforced with TiO2 nanoparticles in order to enhance thermo-mechanical stabilities, surface characteristics and osteoblastic cell adhesion. PVA-TiO2 nanocomposite films with desirable mechanical, thermal and biocompatible properties are fabricated through solution casting method followed by de-hydrothermal cross-linking treatment. The composition of TiO2 nanoparticles was standardized to achieve mechanically stable nanocomposite films, based on tensile strength measurements composition of TiO2 is determined as optimal at 3wt%. PVA-TiO2 nanocomposite films were characterized by Scanning electron microscopy, Energy dispersive spectroscopy, Atomic force microscopy, Ultra violet and Fourier transform infrared spectroscopic techniques. Elemental mapping studies substantiate incorporation of TiO2 nanoparticles within the PVA matrix. Dimensional stability evaluated by soaking films in SBF for 24h insinuates the role of TiO2 in the direction of controlling degree of swelling. In-vitro bioactivity test and cell adhesion results also predict that presence of TiO2 is advantageous to enhance apatite growth and promote cell-substrate interaction. SEM studies illustrate improved surface morphology of PVA-TiO2 nanocomposite film with homogenously distributed TiO2 nanoparticles, which help to enhance thermo-mechanical behavior. TiO2 nanoparticles construct cell-adhesive hydrophilic nano-domains that act as potential cell adhesion sites and promotes osteointegration. Bio compatibility studies proved that thermally cross-linked PVA is non-toxic in relation to PVA cross-linked with glutaraldehyde. Cytotoxicity and cell adhesion of nanocomposite films evaluated through cell viability (MMT) assay and crystal violet staining revealed that PVA-3wt% TiO2nanocomposite could act as an excellent composite and hence suitable to be used in bone implant applications. PMID- 27371871 TI - Evolution of proteolytic and physico-chemical characteristics of Norwegian dry cured ham during its processing. AB - Proteolytic activity and physico-chemical characteristics were studied for Norwegian dry-cured ham at four different times of processing: raw hams, post salted hams (3 months of processing), hams selected in the middle of the production (12 months of processing) and hams at the end of the processing (24 months). Cathepsin H activity decreased until negligible values after 3 months of processing, whereas cathepsins B and B+L were inactive at 12 months. AAP was the most active aminopeptidase whereas RAP and MAP were active just during the first 12 months of processing. Proteolysis index reached a value of 4.56+/-1.03 % with non-significant differences between 12 and 24 months of ripening. Peptide identification by LC-MS/MS was done and two peptides (GVEEPPKGHKGNKK and QAISNNKDQGSY) showing a linear response with the time of processing were found. Unfreezable water content and glass transition temperature were investigated using differential scanning calorimetry (DSC) technique with non-significant differences in the temperature of glass transition for 12 and 24 months of processing. PMID- 27371872 TI - Relocation of Infrapositioned Ankylosed Teeth: Description of Orthodontic Bone Stretching and Case Series. AB - Different treatments have been proposed to manage the consequences of ankylosed teeth. This clinical report, which includes several different clinical conditions, describes an orthodontic bone-stretching procedure that can be used to relocate ankylosed teeth. The orthodontic bone-stretching technique involves only partial osteotomies, without the mobilization or repositioning of the alveolar segment, combined with orthodontic forces. The applied force facilitates tooth movement to the occlusal plane and can modify the axis of the ankylosed tooth. This relocation is possible because of a bone-stretching phenomenon in the surgical area. In all of the cases, relocation of the ankylosed teeth was successfully performed and the gingival margins were corrected to improve the esthetic results. PMID- 27371873 TI - Is Counterclockwise Rotation of the Maxillomandibular Complex Stable Compared With Clockwise Rotation in the Correction of Dentofacial Deformities? A Systematic Review and Meta-Analysis. AB - PURPOSE: To compare postsurgical skeletal stability between counterclockwise rotation (CCWR) of the maxillomandibular complex (MMC) and clockwise rotation (CWR) of the MMC for the correction of dentofacial deformities. MATERIALS AND METHODS: To address the study purpose, we designed and implemented a systematic review with meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search strategy was developed, and a search of major databases-PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL)-was conducted to find all pertinent articles published from inception through March 2016. The inclusion criteria were randomized controlled trials, controlled clinical trials, retrospective studies, and case series with the aim of comparing postsurgical stability of CCWR and CWR of the MMC. The analysis was performed using lateral cephalometric analysis of postsurgical mean values and correlation between the surgical and postsurgical changes of the occlusal plane angle and linear changes at A point and B point. A weighted mean difference analysis using a random-effects model with 95% confidence intervals was performed. RESULTS: A total of 133 patients were enrolled from 3 studies (CCWR, n = 83; CWR, n = 50). All included studies were at moderate risk of bias. There was a statistically significant difference between CCWR and CWR of the MMC in the postsurgical changes of the occlusal plane angle (P = .034), but no statistically significant difference was found in the correlation between the surgical and postsurgical changes of the occlusal plane angle in the 2 groups. There was no statistically significant difference between CCWR and CWR of the MMC for stability between assessments immediately after surgery and at longest follow-up relative to the vertical and horizontal positions at A point and B point (P > .05). CONCLUSIONS: CCWR compared with CWR for the correction of dentofacial deformities in the absence of pre-existing temporomandibular joint pathology is skeletally stable relative to the postsurgical changes of the occlusal plane, as well as the vertical and horizontal changes of the maxilla and mandible. PMID- 27371874 TI - Epiproteomics: quantitative analysis of histone marks and codes by mass spectrometry. AB - Histones are a group of proteins with a high number of post-translational modifications, including methylation, acetylation, phosphorylation, and monoubiquitination, which play critical roles in every chromatin-templated activity. The quantitative analysis of these modifications using mass spectrometry (MS) has seen significant improvements over the last decade. It is now possible to perform large-scale surveys of dozens of histone marks and hundreds of their combinations on global chromatin. Here, we review the development of three MS strategies for analyzing histone modifications that have come to be known as Bottom Up, Middle Down, and Top Down. We also discuss challenges and innovative solutions for characterizing and quantifying complicated isobaric species arising from multiple modifications on the same histone molecule. PMID- 27371875 TI - Advances and challenges in understanding histone demethylase biology. AB - Within the last decade we have witnessed significant progress in the field of chromatin methylation, ranging from the discovery that chromatin methylation is reversible, to the identification of two classes of oxidative chromatin demethylases. Multiple genetic and cellular studies emphasize the role of members of the amine oxidase and 2-oxoglutarate oxygenase enzyme families involved in methyl-lysine in physiology and disease. Advances in understanding of the underlying biochemistry have resulted in development of first series of clinical inhibitors and tool compounds which continue to resolve and help understand the complex relationships between chromatin modification, control of gene expression and metabolic states. PMID- 27371877 TI - Two-Step Forward Genetic Screen in Mice Identifies the Ral Pathway as a Central Drug Target in Hepatocellular Carcinoma. PMID- 27371876 TI - Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-kappaB-mediated inflammation. AB - Activation of inflammatory gene expression is regulated, among other factors, by post-translational modifications of histone proteins. The most investigated type of histone modifications is lysine acetylations. Histone deacetylases (HDACs) remove acetylations from lysines, thereby influencing (inflammatory) gene expression. Intriguingly, apart from histones, HDACs also target non-histone proteins. The nuclear factor kappaB (NF-kappaB) pathway is an important regulator in the expression of numerous inflammatory genes, and acetylation plays a crucial role in regulating its responses. Several studies have shed more light on the role of HDAC 1-3 in inflammation with a particular pro-inflammatory role for HDAC 3. Nevertheless, the HDAC-NF-kappaB interactions in inflammatory signalling have not been fully understood. An important challenge in targeting the regulatory role of HDACs in the NF-kappaB pathway is the development of highly potent small molecules that selectively target HDAC iso-enzymes. This review focuses on the role of HDAC 3 in (NF-kappaB-mediated) inflammation and NF-kappaB lysine acetylation. In addition, we address the application of frequently used small molecule HDAC inhibitors as an approach to attenuate inflammatory responses, and their potential as novel therapeutics. Finally, recent progress and future directions in medicinal chemistry efforts aimed at HDAC 3-selective inhibitors are discussed. PMID- 27371878 TI - Rectal Nonsteroidal Anti-inflammatory Drugs to Reduce the Rate and Severity of Pancreatitis After Endoscopic Retrograde Cholangiopancreatography: Still Grappling With Fundamental Questions. PMID- 27371879 TI - Screening for Celiac Disease in Individuals With Symptoms Suggestive of Irritable Bowel Syndrome: Still a Worthwhile Exercise. PMID- 27371880 TI - PPIs and Chronic Kidney Disease: Another Association to Worry About? PMID- 27371881 TI - Effects of A1 receptor agonist/antagonist on spontaneous seizures in pilocarpine induced epileptic rats. AB - Adenosine is an endogenous anticonvulsant that activates pre- and postsynaptic adenosine A1 receptors. A1 receptor agonists increase the latency for the development of seizures and status epilepticus following pilocarpine administration. Although hippocampal adenosine is increased in the chronic phase of the pilocarpine model, it is not known whether the modulation of A1 receptors may influence the frequency of spontaneous recurrent seizures (SRS). Here, we tested the hypothesis that the A1 receptor agonist RPia ([R]-N phenylisopropyladenosine) and the A1 antagonist DPCPX (8-Cyclopentyl-1,3 dipropylxanthine) administered to chronic pilocarpine epileptic rats would respectively decrease and increase the frequency of SRS and hippocampal excitability. Four months after Pilo-induced SE, chronic epileptic rats were video-monitored for the recording of SRS before (basal) and after a 2-week treatment with RPia (25MUg/kg) or DPCPX (50MUg/kg). Following sacrifice, brain slices were studied with electrophysiology. We found that rats given RPia had a 93% nonsignificant reduction in the frequency of seizures compared with their own pretreatment baseline. In contrast, the administration of DPCPX resulted in an 87% significant increase in seizure rate. Nontreated epileptic rats had a similar frequency of seizures along the study. Corroborating our behavioral data, in vitro recordings showed that slices from animals previously given DPCPX had a shorter latency to develop epileptiform activity, longer and higher DC shifts, and higher spike amplitude compared with slices from nontreated Pilo controls. In contrast, smaller spike amplitude was recorded in slices from animals given RPia. In summary, the administration of A1 agonists reduced hippocampal excitability but not the frequency of spontaneous recurrent seizures in chronic epileptic rats, whereas A1 receptor antagonists increased both. PMID- 27371882 TI - Sexual problems in people with refractory epilepsy. AB - Sexual dysfunction is an important but often neglected aspect of epilepsy. The objective of this study was to explore the prevalence and types of sexual problems in patients with epilepsy and compare the results with similar data obtained from a representative sample of the general population. At the National Centre for Epilepsy in Norway, 171 of 227 consecutive adult inpatients and outpatients with epilepsy (response rate: 75.3%) and their neurologists participated in a questionnaire study about epilepsy and sexuality. The results were compared with data available from 594 adult Norwegians who had completed the same questionnaire. Patients with epilepsy had a significantly higher prevalence of sexual problems (women: 75.3% vs. 12.0%; men: 63.3% vs. 9.6%). The most commonly reported problems (>30%) were reduced sexual desire, orgasm problems, erection problems, and vaginal dryness. The patients reported considerable dissatisfaction regarding sexual functioning. Significantly more sexual problems were found in patients of both sexes with reduced quality of life and in women with symptoms of depression. We found no significant association between sexual problems and age of epilepsy onset, type of epilepsy, or use of enzyme-inducing antiepileptic drugs. Whereas age at sexual debut did not differ between the patients with epilepsy and the general population, men with epilepsy had a lower number of partners during the last 12months, and the proportion of women with a low frequency of intercourse was higher in the group with epilepsy. In conclusion, sexual problems are significantly greater in Norwegian patients with epilepsy than in the general adult population. As no single epilepsy type or treatment could be identified as a specific predisposing factor, it seems likely that there are multiple causes underlying our results, including both organic and psychosocial factors. PMID- 27371883 TI - Putting children forward for epilepsy surgery: A qualitative study of UK parents' and health professionals' decision-making experiences. AB - BACKGROUND: Against a backdrop of recommendations for increasing access to and uptake of early surgical intervention for children with medically intractable epilepsy, it is important to understand how parents and professionals decide to put children forward for epilepsy surgery and what their decisional support needs are. AIM: The aim of this study was to explore how parents and health professionals make decisions regarding putting children forward for pediatric epilepsy surgery. METHODS: Individual interviews were conducted with nine parents of children who had undergone pediatric epilepsy surgery at a specialist children's hospital and ten healthcare professionals who made up the children's epilepsy surgery service multidisciplinary healthcare team (MDT). Three MDT meetings were also observed. Data were analyzed thematically. FINDINGS: Four themes were generated from analysis of interviews with parents: presentation of surgery as a treatment option, decision-making, looking back, and interventions. Three themes were generated from analysis of interviews/observations with health professionals: triangulating information, team working, and patient and family perspectives. DISCUSSION: Parents wanted more information and support in deciding to put their child forward for epilepsy surgery. They attempted to balance the potential benefits of surgery against any risks of harm. For health professionals, a multidisciplinary approach was seen as crucial to the decision making process. Advocating for the family was perceived to be the responsibility of nonmedical professionals. CONCLUSION: Decision-making can be supported by incorporating families into discussions regarding epilepsy surgery as a potential treatment option earlier in the process and by providing families with additional information and access to other parents with similar experiences. PMID- 27371884 TI - A longitudinal, randomized, and prospective study of nocturnal monitoring in children and adolescents with epilepsy: Effects on quality of life and sleep. AB - OBJECTIVE: Most studies on seizure detection systems focus more on the effectiveness of devices than on their practicability in and impact on everyday life. Our study investigated the impact of a technical monitoring system on subjective quality of sleep and the lives of affected families. Furthermore, we evaluated the impact of anxiety levels on seizure monitoring and vice versa. METHODS: Forty-three patients with newly diagnosed epilepsy were included. Initially, the families decided whether they did (group 1, n=27) or did not (group 2, n=16) want to use a monitoring device. In group 1, patients were randomly assigned to using Epi-Care(r) (group 1A, n=14) or an audio baby monitor (group 1B, n=13). Quality of life was assessed at two points (t1, at the start of the study and t2, at 5-7months of follow-up) using the SF-12, Kindl-R, and "Familien-Belastungs-Fragebogen" (German version of the "Impact on Family Scale"). In addition, parental anxiety was measured using the State-Trait Anxiety Inventory, and subjective quality of sleep was measured using the Pittsburgh Sleep Quality Index. Statistical analysis focused on the possible differences between groups 1 and 2 that may influence parents' decisions and the effects of the presence and types of technical monitoring over time. RESULTS: Anxiety levels were not significantly different between the groups with and without monitoring (group 1 vs. group 2). We also found no statistically significant, substantial baseline differences between the Epi-Care(r) and audio baby monitor groups, with at least medium effect sizes (group 1A vs. group 1B). Parents' health-related mental quality of life measured via the SF-12 increased significantly over time in all groups. By tendency, the fear of further seizures as well as the frequency of cosleeping arrangements in the monitoring group decreased during the study and approached the stable values of the control group. SIGNIFICANCE: Individual parental anxiety levels are not crucial in the decision regarding the use of a monitoring device. A monitoring system may help some families in certain aspects of daily life. During the first months following a diagnosis of epilepsy, quality of life increases independently of the use of a monitoring system. PMID- 27371885 TI - The psychosocial impact of exercising with epilepsy: A narrative analysis. AB - Research has presented the benefits of and barriers to exercise for people with epilepsy through quantitative means. However, individual experiences through qualitative investigations have been absent. This research will present the narratives of people with epilepsy exercising over time and, as a result, develop further understanding of the psychosocial impact of exercising with epilepsy. Four interviews were conducted over the course of one year (one every three to four months) with four participants (aged 23-38years) who varied in seizure type and control (16 interviews in total). A narrative analysis was used to analyze their exercise experiences. Results showed that exercise creates a positive effect on psychological and physical well-being. However, prevention from exercise as a result of medical advice or recurrent seizures can create negative effects such as social isolation, anxiety, lack of confidence, frustration, and anger. Adaptations of decreasing exercise intensity level and partaking in different physical activities are techniques used to lessen the negative impact and maintain an exercise routine. Time was shown to be an important factor in this adaptation as well as portrayed the cyclical responses of negative and positive emotions in regard to their exercise life. These findings provide valuable insight into the psychosocial benefits of and barriers to exercising with epilepsy and draw attention to the individual differences in how a person with epilepsy copes with uncontrolled seizures and their impact on his/her exercise routine. This knowledge can lead to future research in exploring how a person with epilepsy can overcome these barriers to exercise and encourage more people with epilepsy to enjoy the benefits of exercise. PMID- 27371887 TI - Choosing and succeeding in academic medicine: advice for students, trainees, and junior faculty. PMID- 27371888 TI - CD4 and CD4/CD8 ratio progression in HIV-HCV infected patients after achievement of SVR. AB - BACKGROUND: In HIV-HCV co-infected patients, the long-term effects of HCV eradication on HIV disease progression are still unclear. OBJECTIVES: This study aims to determine if CD4 and CD4/CD8 ratio slopes improved after anti-HCV treatment in patients achieving a sustained virological response (SVR). STUDY DESIGN: A total of 116 HIV-HCV co-infected patients, previously treated with Peg IFN/RBV, were divided into two groups: SVR (55 patients who had achieved SVR), and non-SVR (61 patients). Retrospective data before and after anti-HCV therapy were obtained for all patients, with a median 8 year-follow-up. Multilevel mixed models were fitted to assess the trends over time of FIB-4 score, APRI score, CD4, CD8 cell count and CD4/CD8 ratio. RESULTS: Median HIV-infection duration, HCV-RNA and GGT baseline levels were higher in non-SVR compared to the SVR group. A significantly decreased FIB-4 (p<0.001) and APRI trend (p<0.001) after SVR was observed in SVR patients compared to those non-SVR. After adjustment for HIV duration, there was no significant difference between the two groups for absolute CD4 (p=0.08) or percentage CD4 slope (p=0.6) over time. The CD4/CD8 ratio trend also demonstrated a similar progressive increase in both groups (p=0.2). During follow-up, six deaths were reported in the non-SVR group versus no death for the SVR group, while no difference in AIDS and non-AIDS events was observed. CONCLUSIONS: Achievement of SVR determines an important beneficial impact in terms of liver-related mortality and fibrosis regression, but does not seem to alter neither the slope of long term CD4 gain nor the CD4/CD8 ratio evolution in ART-treated HIV-HCV co-infected patients. PMID- 27371886 TI - The gut microbiota and inflammatory bowel diseases. AB - Inflammatory bowel diseases (IBDs) are chronic diseases of unclear etiology that affect over 1 million individuals in the United States and over 2.5 million people in Europe. However, they are also expanding globally, affecting populations in Asia, South America, and the Middle East as they become more industrialized. These diseases are believed to arise from the convergence of genetic, environmental, and microbial factors that trigger aberrant immune and tissue responses, resulting in intestinal inflammation. Advances in cultivation independent investigations, experimental models, and bioinformatics approaches have improved our understanding of the role of gut microbiota in IBD. However, determining and understanding the functional consequences of gut dysbiosis and altered host-microbiota interactions in IBD remain a challenge due to the limits of current experimental models and difficulty in establishing causal links in human-based investigations. Continued development of new methodologies and improvements in clinical study design are needed to better understand the interplay of genetic, microbial, and immunological factors in IBD. This knowledge can then be applied clinically to improve therapeutic strategies and outcomes for IBD. PMID- 27371889 TI - The dynamic mechanical properties of cellularised aggregates. AB - Cellularised materials are composed of cells interfaced through specialised intercellular junctions that link the cytoskeleton of one cell to that of its neighbours allowing for transmission of forces. Cellularised materials are common in early development and adult tissues where they can be found in the form of cell sheets, cysts, or amorphous aggregates and in pathophysiological conditions such as cancerous tumours. Given the growing realisation that forces can regulate cell physiology and developmental processes, understanding how cellularised materials deform under mechanical stress or dissipate stress appear as key biological questions. In this review, we will discuss the dynamic mechanical properties of cellularised materials devoid of extracellular matrix. PMID- 27371890 TI - Identification and binding mechanism of phage displayed peptides with specific affinity to acid-alkali treated titanium. AB - Acid-alkali treatment is one of means widely used for preparing bioactive titanium surfaces. Peptides with specific affinity to titanium surface modified by acid-alkali two-steps treatment were obtained via phage display technology. Out of the eight new unique peptides, titanium-binding peptide 54 displayed by monoclonal M13 phage at its pIII coat protein (TBP54-M13 phage) was proved to have higher binding affinity to the substrate. The binding interaction occurred at the domain from phenylalanine at position 1 to arginine at position 6 in the sequences of TBP54 (FAETHRGFHFSF) mainly via the reaction of these residues with the Ti surface. Together the coordination and electrostatic interactions controlled the specific binding of the phage to the substrate. The binding affinity was dependent on the surface basic hydroxyl group content. In addition, the phage showed a different interaction way with the Ti surface without acid alkali treatment along with an impaired affinity. This study could provide more understanding of the interaction mechanism between the selected peptide and its specific substrate, and develop a promising method for the biofunctionalization of titanium. PMID- 27371891 TI - Phenylboronic acid-functionalized polyamidoamine-mediated Bcl-2 siRNA delivery for inhibiting the cell proliferation. AB - In this study, the conjugation of phenylboronic acid (PBA) to amine-terminated polyamidoamine (PAMAM) was successfully conducted to prepare a tumor-targeted gene carrier PBA-functionalized PAMAM (PPP) for Bcl-2 siRNA delivery, using a heterobifunctional crosslinker NHS-PEG5k-Mal. The carrier possessed favorable capacity for siRNA condensation and could protect siRNA from the degradation against RNase and serum. The introduction of PBA could facilitate the cellular uptake and further transfection of Bcl-2 siRNA demonstrated by confocal laser scanning microscopy and flow cytometry. Meanwhile, PPP-mediated transfection of Bcl-2 siRNA could significantly inhibit the expression of Bcl-2 gene at both mRNA and protein levels. Furthermore, owing to the knock-down of Bcl-2, PPP/siRNA could significantly inhibit the cell proliferation by inducing the cell apoptosis, and also enhance the antitumor efficiency of doxorubicin by suppressing the resistance of tumor cells to chemotherapeutics. In conclusion, the PPP-mediated Bcl-2 siRNA delivery could potentially be an effective platform for solving the drug resistance and further achieving the combined chemotherapy and gene therapy in tumor treatment. PMID- 27371893 TI - A novel gelatin-based micro-cavitary hydrogel for potential application in delivery of anchorage dependent cells: A study with vasculogenesis model. AB - Hydrogels have been widely regarded as promising tissue engineering scaffolds and cell delivery vehicles, however, their inherent submicron- or nano-scale polymer networks severely inhibit the settlement of anchorage dependent cells (ADCs). Here, using endothelial progenitor outgrowth cells (EPOCs) as the typical ADCs, a gelatin-based micro-cavitary gel (namely Gel-MCG) is developed with gelatin methacrylate and gelatin microspheres as precursor and porogens, respectively, to promote cellular focal adhesion and functions. The introduction of micro-cavitary structures within the Gel-MCG improves its physical properties as well as creates numerous gel-microcavity interfaces within gel-based matrices. Compared with conventional gelatin gel (Gel-G) scaffold, the Gel-MCG provides more suitable microenvironments for EPOCs' attachment, spreading, and proliferation, and then which leads to enhanced endothelial differentiation and vascularization as demonstrated by higher expressions of endothelial markers. The Gel-MCG system shows great potential as vehicle for the delivery of ADCs in tissue engineering. PMID- 27371892 TI - A robust way to prepare blood-compatible and anti-fouling polyethersulfone membrane. AB - Functional copolymers were successfully grafted onto polyethersulfone (PES) membrane surfaces by free radical mechanism using ammonium persulfate (APS) as an initiator. The anti-coagulant and anti-fouling properties of the membranes were well controlled by changing the functional copolymer compositions. Attenuated total reflection-Fourier transforminfrared (ATR-FTIR), X-ray photoelectron spectrometer spectrum (XPS), water contact angles (WCAs), and scanning electron microscopy (SEM) images were used to characterize the membranes. The results of protein adsorption, clotting times, platelet adhesion and bacteria attachment indicated that the membranes had good blood-compatibility and/or anti-fouling ability. Meanwhile, the modification didn't cause an adverse effect on the membrane permeability. This new method provides a general, robust and flexible way to adjust membrane surface performance and potentially has wide applications. PMID- 27371894 TI - Redox-responsive minimized fragmentation of three-armed oligo(ethylene glycol) gels for protein release. AB - Redox-responsive drug delivery system (DDS) carriers cross-linked by disulfide bonds have attracted attention, because disulfide bonds can be cleaved in the presence of high glutathione (GSH) concentrations found in cancer cells. In this study, to obtain redox-responsive degradable hydrogels, three-armed oligo(ethylene glycol) (trisOEG) gels were prepared through terminal cross linking reaction that linked together low-molecular-weight trisOEG molecules via a disulfide bond. The stability of the trisOEG gels was investigated in the presence of a reductant, dithiothreitol (DTT) or reduced GSH, in phosphate buffered saline solution. TrisOEG gels were fragmented by a redox-stimulus, returning the decomposed hydrophilic oligomers to a low-molecular-weight state, similar to the raw material that would be expected to be excreted in vivo by the renal system. In addition, protein-immobilized trisOEG micro-gels were prepared. While no release of entrapped protein from trisOEG micro-gel was observed in the absence of GSH, release of entrapped protein was observed in the presence of GSH at a concentration found in cytoplasm. PMID- 27371895 TI - Polymeric membranes modulate human keratinocyte differentiation in specific epidermal layers. AB - In vitro models of human bioengineered skin substitutes are an alternative to animal experimentation for testing the effects and toxicity of drugs, cosmetics and pollutants. For the first time specific and distinct human epidermal strata were engineered by using membranes and keratinocytes. To this purpose, biodegradable membranes of chitosan (CHT), polycaprolactone (PCL) and a polymeric blend of CHT-PCL were prepared by phase-inversion technique and characterized in order to evaluate their morphological, physico-chemical and mechanical properties. The capability of membranes to modulate keratinocyte differentiation inducing specific interactions in epidermal membrane systems was investigated. The overall results demonstrated that the membrane properties strongly influence the cell morpho-functional behaviour of human keratinocytes, modulating their terminal differentiation, with the creation of specific epidermal strata or a fully proliferative epidermal multilayer system. In particular, human keratinocytes adhered on CHT and CHT-PCL membranes, forming the structure of the epidermal top layers, such as the corneum and granulosum strata, characterized by withdrawal or reduction from the cell cycle and cell proliferation. On the PCL membrane, keratinocytes developed an epidermal basal lamina, with high proliferating cells that stratified and migrated over time to form a complete differentiating epidermal multilayer system. PMID- 27371896 TI - Clinical efficacy and safety of eperisone for low back pain: A systematic literature review. AB - Eperisone, an analgesic and centrally acting muscle relaxant has been in use for the treatment of low back pain (LBP). The present systematic review evaluates the efficacy and safety of eperisone in patients with LBP. Cochrane Back and Neck (CBN) Group and Preferred Reporting Items for Systematic reviews and Meta Analyses (PRISMA) guidelines were adopted to perform this systematic review. For risk of bias assessment CBN Group and Moga tools were used. Seven (5 randomized controlled trials [RCTs] and 2 uncontrolled studies) studies involving 801 participants were included. Eperisone intervention may be effective in acute LBP patients with less adverse effects (relative risk, 0.25; 95% confidence interval, 0.15-0.41; p<0.0001). Eperisone also improved paraspinal blood flow and was found to have efficacy similar to tizanidine in chronic LBP patients. The included studies in this review are of smaller sample size and short duration to support eperisone use in LBP. However, we recommend well-designed RCTs of high quality with larger sample size and longer follow-up to confirm the clinical benefits of eperisone in the treatment of acute or chronic LBP. PMID- 27371897 TI - Protective effects of MCR-1329, a dual alpha1 and angII receptor antagonist, in mineralocorticoid-induced hypertension. AB - BACKGROUND: With the prototypical structures of losartan and prazosin as the axis of our research, MCR-1329 emerged as a potential designed multiple ligand from a series of compounds designed to possess dual antagonistic activity on the alpha1 and AT1 receptor. After confirming the activity of MCR-1329 in in vitro and acute in vivo models, the present study was undertaken to determine the efficacy of MCR 1329 in a mammalian test system. METHODS: A rat model of deoxycorticosterone acetate (DOCA)-salt induced renal hypertension following unilateral nephrectomy was utilized to determine the effect of MCR-1329. For mechanistic evaluations, MCR-1329 was evaluated on rat aortic strips in vitro and on rat aortic smooth muscle cells to determine the role of MCR-1329 on phosphoinositide 3 kinase (PI3K) signaling. RESULTS: Results of the study showed that MCR-1329 prevents development of arterial hypertension. It was also observed that MCR-1329 upheld the intimal structures of major arteries like the thoracic aorta. Acetylcholine (Ach)-mediated relaxation remained intact in arteries from MCR-1329 treated animals. It was observed that MCR-1329 partially prevents Thr-308 phosphorylation of Akt following ligand-mediated receptor stimulation in vascular smooth muscle cells. Addition of LY294002 to the reaction medium caused a near-complete inhibition of Akt-phosphorylation. This suggested that MCR-1329 elicits its antihypertensive role by blocking activation of receptor-mediated PI3K-Akt downstream signaling as well as through preservation of arterial integrity. CONCLUSIONS: MCR-1329 has the potential to be evaluated further for clinical development as a potential antihypertensive agent with multiple mechanisms of action. PMID- 27371898 TI - Traxoprodil augments the antidepressant-like activity of agomelatine but not of mianserin or tianeptine in the forced swim test in mice. AB - BACKGROUND: The main objective of our study was to evaluate the influence of traxoprodil on the activity of the atypical antidepressant drugs (agomelatine, mianserin, tianeptine). METHODS: The forced swim test (FST) in mice was used to determine the antidepressant-like activity of the tested agents. Drugs levels in brain tissue were assessed by a high performance liquid chromatography method. RESULTS: Concurrent intraperitoneal administration of per se ineffective doses of traxoprodil (10mg/kg) and agomelatine (20mg/kg) shortened the immobility time of animals in the FST. The observed effect was associated with elevated brain levels of traxoprodil. Similar interaction was not detected for traxoprodil and mianserin (10mg/kg) or tianeptine (15mg/kg). CONCLUSION: Traxoprodil-agomelatine interaction is pharmacokinetic in nature. A combination of these agents has a potential to become an interesting strategy in the treatment of depression. PMID- 27371899 TI - Inflammation influences steroid hormone receptors targeted by progestins in endometrial stromal cells from women with endometriosis. AB - Endometriosis is an estrogen-dependent disease characterised by the growth of endometrial epithelial and stromal cells outside the uterus creating a chronic inflammatory environment that further contributes to disease progression. The first choice treatment for endometriosis is currently progestin mediated hormone modulation. In addition to their progestogenic activity however, progestins also have the potential to bind to other nuclear receptors influencing their local activity on endometriotic cells. This local activity will be dependent on the steroid hormone receptor expression that occurs in endometrial cells in a chronic inflammatory environment. We therefore aimed to quantify receptors targeted by progestins in endometrial stromal cells after exposure to inflammation. Using primary endometrial stromal cells isolated from women with endometriosis we examined the mRNA and protein expression of the progesterone receptors A and B, membrane progesterone receptors 1 and 2, androgen receptors, mineralocorticoid receptors and glucocorticoid receptors after exposure to the inflammatory cytokines tumor necrosis factor alpha (TNFalpha) and interleukin 1beta (IL 1beta). The results indicate that both cytokines reduced the expression of progesterone receptors and increased the expression of the glucocorticoid receptors in the endometrial stromal cells. The change in expression of progestin targets in endometrial stromal cells in an inflammatory environment could contribute to the progesterone resistance observed in endometriotic cells and ultimately influence the design of hormonal therapies aimed at treating this disease. PMID- 27371900 TI - Increased percentage of Th17 cells in peritoneal fluid is associated with severity of endometriosis. AB - AIM: Th17 cells are a newly discovered T helper lymphocyte subpopulation, producing interleukin IL-17. Th17 cells are present in blood and peritoneal fluid (PF) at different stages of endometriosis. We aim to establish their potential importance in the pathogenesis and clinical features of the disease. METHODS: The percentage of Th17 cells among T helper lymphocytes was determined in the PF and peripheral blood (PB) of patients with endometriosis and in the control group by flow cytometry using monoclonal antibodies: anti-CD-4-FITC, anti-CD-3-PE/Cy5, and anti-IL-17A-PE. RESULTS: Th17 percentage is increased in PF in comparison with PB in both endometriotic patients and in the control group. In severe endometriosis, the percentage of Th17 cells in PF was higher than with early (I/II stage) endometriosis. A positive correlation between the percentage of Th17 cells in PF and the white blood cell count in PB was found in patients with endometriosis. CONCLUSION: Targeting the activity of PF Th17 cells may have an influence on the proliferation of ectopic tissue and clinical manifestations of the disease. PMID- 27371901 TI - Body mass index reference charts for individuals with Down syndrome aged 2-18 years. AB - OBJECTIVE: To develop Brazilian growth charts for body mass index (BMI-for-age) for individuals with Down syndrome (DS). The secondary objective was to compare the BMI-for-age with the Centers for Disease Control and Prevention standards (CDC). METHODS: A retrospective and cross-sectional growth study of 706 youth with DS (56.7% males) was performed in 51 centers in Sao Paulo state, Brazil. Weight and height were used to calculate the BMI (kg/m2). The LMS method was applied to construct the growth charts. Z-scores were based on the CDC 2000 growth standards. RESULTS: The BMI-for-age reference charts showed excellent goodness of fit statistics for boys and girls with DS aged 2-18 years. At 2 years of age, the mean BMI Z-scores of boys and girls with DS were lower compared to those of the CDC (Z-score=-0.2). In contrast, children with DS aged 3-18 years had higher mean Z-scores for BMI-for-age when compared to those of the CDC (Z scores=+0.2 to +1.3). CONCLUSIONS: The BMI of Brazilian youth with DS differs from those references established by CDC. These are the first Brazilian BMI-for age charts for individuals with DS and will hopefully guide clinicians and parents in the evaluation and management of the nutritional status in children and adolescents with DS in Brazil. PMID- 27371902 TI - Analysis of microbiota on abalone (Haliotis discus hannai) in South Korea for improved product management. AB - Abalone is a popular seafood in South Korea; however, because it contains various microorganisms, its ingestion can cause food poisoning. Therefore, analysis of the microbiota on abalone can improve understanding of outbreaks and causes of food poisoning and help to better manage seafood products. In this study, we collected a total of 40 abalones from four different regions in March and July, which are known as the maximum abalone production areas in Korea. The microbiota were analyzed using high-throughput sequencing, and bacterial loads on abalone were quantified by real-time PCR. Over 2700 species were detected in the samples, and Alpha- and Gammaproteobacteria were the predominant classes. The differences in microbiota among regions and at each sampling time were also investigated. Although Psychrobacter was the dominant genus detected on abalone in both March and July, the species compositions were different between the two sampling times. Five potential pathogens (Lactococcus garvieae, Yersinia kristensenii, Staphylococcus saprophyticus, Staphylococcus warneri, and Staphylococcus epidermidis) were detected among the abalone microbiota. In addition, we analyzed the influence of Vibrio parahaemolyticus infection on shifts in abalone microbiota during storage at different temperatures. Although the proportion of Vibrio increased over time in infected and non-infected abalone, the shifts of microbiota were more dynamic in infected abalone. These results can be used to better understand the potential of food poisoning caused by abalone consumption and manage abalone products according to the microbiota composition. PMID- 27371903 TI - The use of propidium monoazide in conjunction with qPCR and Illumina sequencing to identify and quantify live yeasts and bacteria. AB - Culture-independent methods of microbial identification have been developed, which allow for DNA extraction directly from environmental samples without subjecting microbes to growth on nutrient media. These methods often involve next generation DNA sequencing (NGS) for identifying microbes and qPCR for quantifying them. Despite the benefits of extracting all DNA from the sample, results may be compromised by amplifying DNA from dead cells. To address this short-coming, the use of propidium monoazide (PMA) has been used to deactivate DNA in non-viable cells. Nevertheless, its optimization has not been fully explored under a variety of conditions. In this study, we optimized the PMA method for both yeasts and bacteria. Specifically, we explored the effect different PMA concentrations and different cell densities had on DNA amplification (as part of next generation DNA sequencing) from both dead and viable bacterial and yeast cells. We found PMA was effective in eliminating DNA that was associated with dead yeast and bacterial cells for all cell concentrations. Nevertheless, DNA (extracted from viable yeast and bacterial cells) amplified most abundantly when PMA concentration was at 6MUM and when yeast densities ranged between 10(6) to 10(7)CFU/mL and bacterial densities were approximately 10(8)CFU/mL. PMID- 27371904 TI - Trunk muscle reflexes are elicited by small continuous perturbations in healthy subjects and patients with low-back pain. AB - Low-back pain (LBP) has been recognized as the leading cause of disability worldwide. Lumbar instability has been considered as an important mechanism of LBP and one potential contributor to lumbar stability is trunk muscle reflex activity. However, due to the differences in experimental paradigms used to quantify trunk mechanics and trunk reflexes it remains unclear as to what extent the reflex pathway contributes to overall lumbar stability. The goal of this work was to determine to what extent reflexes of various trunk muscles were elicited by the small continuous perturbations normally used to quantify trunk mechanics. Electromyographic (EMG) activity was measured bilaterally from 3 trunk extensor muscles and 3 trunk flexor muscles at four epochs: 25-50ms, 50-75ms, 75-100ms and 100-125ms following each perturbation. Reflex activity was seen in all muscles as 34 of the 48 muscle-epoch combinations showed a significant reflex response to either perturbations in the forward or backward direction. However, the reflex EMG activity did not correlate with mechanical estimates of the reflex response. Thus, even though reflexes are indeed elicited by the small perturbations used to quantify trunk mechanics, their exact contribution to overall lumbar stability remains unknown. PMID- 27371905 TI - Effects of whole body vibration on muscle contractile properties in exercise induced muscle damaged females. AB - Determining muscle contractile properties following exercise is critical in understanding neuromuscular function. Following high intensity training, individuals often experience exercise induced muscle damage (EIMD). The purpose of this investigation was to determine the effect of whole-body vibration (WBV) on muscle contractile properties following EIMD. Twenty-seven females volunteered for 7 sessions and were randomly assigned to a treatment or control group. Muscle contractile properties were assessed via voluntary torque (VT), peak twitch torque (TT), time to reach peak torque, half relaxation time of twitch torque, percent activation (%ACT), rate of rise (RR), rate of decline (RD), mean and peak electromyography during maximum voluntary isometric contraction. Two testing sets were collected each day, consisting of pre measures followed by WBV or control and post measures. A mixed factor analysis of variance was conducted for each variable. %ACT measures found baseline being less than day 1 in both measures in the control group. TT was found to be greater in the control group compared to WBV group. TT and VT baseline measures were greater than all other time points. RR showed control group had higher values than WBV group. These results indicate that WBV following EIMD had some positive effects on muscle contractile properties. PMID- 27371906 TI - Medically unexplained somatic symptoms and bipolar spectrum disorders: A systematic review and meta-analysis. AB - BACKGROUND: Patients with bipolar spectrum disorders (BSD) frequently report medically unexplained somatic symptoms. However, the prevalence and the consequences for treatment and outcome are currently unknown. METHODS: To estimate the prevalence of somatic symptoms in BSD, we conducted a systematic review and meta-analysis of empirical studies published between 1980 and 2015. The odds for somatic symptoms in BSD were compared with unipolar depression (UPD) and general population or mixed psychiatric controls. Studies were retrieved from four electronic databases utilizing Boolean operations and reference list searches. Pooled data estimates were derived using random-effects methods. RESULTS: Out of 2634 studies, 23 were eligible for inclusion, yielding an N of 106,785 patients. The estimated prevalence of somatic symptoms in BSD was 47.8%. The estimated prevalence of BSD in persons with somatic symptoms was 1.4%. Persons with BSD had a higher prevalence of somatic symptoms compared with population or mixed psychiatric controls (OR 1.82, 95% CI 1.14-2.92). Persons with BSD had a similar prevalence of somatic symptoms compared with UPD controls (OR 0.99, 95% CI 0.68-1.44). LIMITATIONS: This study is correlational; thus causal inferences cannot be made. Reporting of somatic symptoms likely varies with BSD severity and subtype. Some studies reported insufficient information regarding comorbid medical conditions and medications. CONCLUSIONS: Persons with BSD suffer from somatic symptoms at a rate nearly double that of the general population, a rate similar to persons with UPD. Our results suggest the utility of an integrated care model in which primary care and specialist physicians collaborate with mental health professionals to jointly address psychological and bodily symptoms. PMID- 27371907 TI - Identifying depression with the PHQ-2: A diagnostic meta-analysis. AB - BACKGROUND: There is interest in the use of very brief instruments to identify depression because of the advantages they offer in busy clinical settings. The PHQ-2, consisting of two questions relating to core symptoms of depression (low mood and loss of interest or pleasure), is one such instrument. METHOD: A systematic review was conducted to identify studies that had assessed the diagnostic performance of the PHQ-2 to detect major depression. Embase, MEDLINE, PsychINFO and grey literature databases were searched. Reference lists of included studies and previous relevant reviews were also examined. Studies were included that used the standard scoring system of the PHQ-2, assessed its performance against a gold-standard diagnostic interview and reported data on its performance at the recommended (>=3) or an alternative cut-off point (>=2). After assessing heterogeneity, where appropriate, data from studies were combined using bivariate diagnostic meta-analysis to derive sensitivity, specificity, likelihood ratios and diagnostic odds ratios. RESULTS: 21 studies met inclusion criteria totalling N=11,175 people out of which 1529 had major depressive disorder according to a gold standard. 19 of the 21 included studies reported data for a cut-off point of >=3. Pooled sensitivity was 0.76 (95% CI =0.68-0.82), pooled specificity was 0.87 (95% CI =0.82-0.90). However there was substantial heterogeneity at this cut-off (I(2)=81.8%). 17 studies reported data on the performance of the measure at cut-off point >=2. Heterogeneity was I(2)=43.2% pooled sensitivity at this cut-off point was 0.91 (95% CI =0.85-0.94), and pooled specificity was 0.70 (95% CI =0.64-0.76). CONCLUSION: The generally lower sensitivity of the PHQ-2 at cut-off >=3 than the original validation study (0.83) suggests that >=2 may be preferable if clinicians want to ensure that few cases of depression are missed. However, in situations in which the prevalence of depression is low, this may result in an unacceptably high false-positive rate because of the associated modest specificity. These results, however, need to be interpreted with caution given the possibility of selectively reported cut-offs. PMID- 27371908 TI - Peer counselling for doctors in Norway: A qualitative study of the relationship between support and surveillance. AB - RATIONALE: Peer support can entail collegial responsibility for counselling and support as well as reactions to academic or ethical failure. These considerations can be complementary, but also conflicting. OBJECTIVE: This article focuses on how the peer support programme in Norway addresses these considerations. METHODS: Focus group interviews held with Norwegian peer counsellors from August 2011 to June 2012 were analysed by a stepwise deductive-inductive method. RESULTS: Based on organisational theory, two "ideal types" of counsellors were identified from the data, and these were then used to reanalyse the text. We found that the organisational framework is associated with the peer counsellors' role conception and thereby the relationship between the counsellor and the help-seeking doctor. The relationship between informal frameworks like collegiality, confidence and discretion, and more formalized incentive-driven frameworks, appear to influence the accessibility to peer support, the mandate to provide relevant help and the understanding of what peer support represents. CONCLUSION: The study showed the need for a continuous awareness of a balance between the informal and the more formalized elements in the framework for peer support. This is of importance for how the service can contribute to better health among doctors and to secure quality and safety in the treatment of patients. The analysis can also be used to demonstrate the consequences of how the peer support program is designed - such as the degree of formalisation and the balance between "hard" and "soft" ways to regulate the interaction between peer counsellors and doctors - for the ability to achieve the stated objectives of the service. PMID- 27371909 TI - Polytherapy with sodium channel-blocking antiepileptic drugs is associated with arrhythmogenic ST-T abnormality in patients with epilepsy. AB - PURPOSE: Recent reports have documented the appearance of Brugada-type ST elevation in cases of overdose of antiepileptic drugs (AEDs). However, little is known about changes on electrocardiographs (ECGs) during AED use at therapeutic doses. AEDs may cause Brugada-type ST elevation or J-wave-like intraventricular conduction delays through an ion channel-blocking effect. In the present study, we sought to elucidate ECG abnormalities in patients on AED therapy. METHODS: The study population consisted of 120 consecutive patients with epilepsy who continued to take AEDs and had ECGs recorded during these therapies. Their clinical background and ECGs were retrospectively analyzed. Brugada-type ST elevation was classified according to the consensus report on Brugada syndrome. A J-wave-like ECG abnormality was defined as the appearance of notching or slurring of the QRS complex (>0.1mV) in the inferior/lateral leads. RESULTS: Of the 120 patients, 15 (12.5%) exhibited Brugada-type ST elevation and 35 (29.2%) showed a J-wave-like ECG abnormality. Polytherapy with sodium channel-blocking AEDs (e.g., carbamazepine, phenytoin, lamotrigine) was more frequently observed in patients with Brugada-type ST elevation (p=0.048). However, the serum concentrations of these medicines did not differ between patients with and without ECG abnormalities (carbamazepine: 7.9+/-4.1 vs. 7.2+/-5.9MUg/dL; phenytoin: 12.7+/ 4.1 vs. 15.5+/-9.5MUg/dL, NS). CONCLUSION: ST-T abnormalities were frequently seen in patients using AEDs. The presence of Brugada-type ST elevation was associated with polytherapy with sodium channel-blocking AEDs. PMID- 27371910 TI - Considerations and challenges for patients with refractory and relapsed acute myeloid leukaemia. AB - Despite advances in understanding the complexities of acute myeloid leukaemia (AML), the treatment of refractory or relapsed AML (rrAML) remains a daunting clinical challenge. Numerous clinical trials have failed to identify new treatments or combinations of existing therapies that substantially improve outcomes and survival. This may be due, at least in part, to heterogeneity among study patients with respect to multiple inter-related factors that have been shown to affect treatment outcomes for patients with rrAML; such factors include age, cytogenetics, immunophenotypic changes, and (in the case of relapsed AML) duration of first complete remission, or if the patient has had a previous blood and marrow transplant (BMT). A clear understanding of disease characteristics and patient-related factors that influence treatment response, as well as expected outcomes with existing and emerging therapies, can aid clinicians in helping their patients navigate through this complex disease state. PMID- 27371911 TI - The many unanswered questions related to the German skin cancer screening programme. AB - In 2008, the first nationwide skin cancer screening (SCS) programme in the world was established in Germany. The main reason to implement the SCS programme in Germany was the expected reduction of costs of care due to earlier detection of skin cancer. The aim of this commentary is to raise and discuss several unanswered questions related to the German SCS programme. The evidence of a temporary mortality decline of skin melanoma after SCS in Schleswig-Holstein is lower than previously assumed and the temporary decline may have been caused by other factors than screening (e.g. awareness effects, selection bias, data artifact, and random fluctuation). The evaluation of the nationwide effect of SCS on skin cancer mortality is hampered by birth cohort effects and low quality of the routine cause-of-death statistics. The nationwide skin melanoma mortality did not decrease from 2007 through 2014. The time interval between screenings after a screening without pathological findings is unclear. Appropriate research designs are needed that monitor and evaluate the effect of SCS not only on skin cancer mortality but also on other factors that may help to judge the potential benefits and harms of SCS including aggressiveness of therapy, costs of care, quality of life, and stage-specific incidence rates of skin cancer. Furthermore, SCS may profit from a high-risk strategy instead of population-wide screening and from newer technologies for early detection of skin cancer (e.g. dermoscopy). PMID- 27371912 TI - Synthesis, characterization and pharmacological studies of copper complexes of flavone derivatives as potential anti-tuberculosis agents. AB - Novel series of different hydroxyflavone derivatives and their copper complexes were synthesized. They were characterized using analytical and spectral techniques. The superoxide dismutase (SOD) mimetic activity of the synthesized complexes demonstrated that copper complex of L(10) has promising SOD-mimetic activity than other ligands & complexes. The in vitro antimicrobial activities of the synthesized compounds were tested against the bacterial species and fungal species. The DNA binding properties of copper complexes were studied using cyclic voltametry and electronic absorption techniques. Anti-tuberculosis activity was also performed. The effective complexes was subjected to antimycobacterial activity using MABA method and summarized. The antimycobacterial activity of copper complexes have been evaluated and discussed. PMID- 27371913 TI - Liposomal nanoformulations of rhodamine for targeted photodynamic inactivation of multidrug resistant gram negative bacteria in sewage treatment plant. AB - The antimicrobial photodynamic therapy is an alternative method for killing bacterial cells in view of the rising problem of antibiotic resistance microorganisms. The present study examined the effect of a water soluble photosensitizer, Rhodamine 6G (R6G) in stealth liposomes on multidrug resistant Pseudomonas aeruginosa in the presence of visible light. Liposomes were prepared with cholesterol and phospholipids that extracted from hen eggs in a cost effective way and characterized by light microscopy, particle size analyzer, electron microscopy, steady state spectrophotometry and spectrofluorometry. The photoefficacies of R6G in polymer encapsulated liposomes and positively charged liposomes are much higher compared to the free R6G (R6G in water) in terms of singlet oxygen quantum yield. This high potential of producing more reactive oxygen species (ROS) by liposomal nanoformulated R6G leads to efficient photodynamic inactivation of multidrug resistant gram negative bacteria in waste water. Though the singlet oxygen quantum yield of polymer coated liposomal R6G was higher than the cationic liposomal formulation, a faster decrease in bacterial survival was observed for positively charged liposomal R6G treated bacteria due to electrostatic charge interactions. Therefore, it can be concluded that the positively charged liposomal nanoformulations of laser dyes are efficient for photodynamic inactivation of multiple drug resistant gram negative microorganisms. PMID- 27371914 TI - Improving the luminescence properties of aequorin by conjugating to CdSe/ZnS quantum dot nanoparticles: Red shift and slowing decay rate. AB - Changing the properties of photoprotein aequorin such as the wavelength emission and decay half-life by using bioluminescence resonance energy transfer (BRET) phenomenon is the main aim in this paper. BRET system was set up with CdSe/ZnS quantum dot nanoparticles as an acceptor molecule and photoprotein as an energy donor molecule. Quantum dots are semiconductor nanoparticles with very interesting optical properties, including broad excitation spectra, narrow and the symmetric band width emission spectra, tunable by their sizes, compositions, negligible photo-bleaching and good chemical and photo-stability. In this QD-BRET system, aequorin is conjugated to the carboxyl groups on quantum dot surface by EDC/NHS chemistry as cross linker. Bioluminescence energy generates by aequorin upon adding Ca(2+) and transfers to the quantum dots in a radiationless manner and emits at a longer wavelength. The determined bioluminescent parameters for this method included aequorin activity, emission spectra and decay half-life time. In fact, this spectrum tuning strategy resulted in a change in bioluminescent properties of photoprotein, therefore, the maximum emission wavelength shifted from 455 to 540nm and the decay time increased from 3.76 to 12.11s. Nowadays, photoproteins with different characteristics are capable of being employed as a reporter in multi-analyte detections and in vivo imaging. PMID- 27371915 TI - Spectroscopic investigation of biosynthesized nickel nanoparticles and its larvicidal, pesticidal activities. AB - Methanolic extract of Cocos nucifera (C. nucifera) was collected using Soxhlet apparatus. C. nucifera methanolic extract was used to prepare Nickel nanoparticles (Ni NPs). Eco-friendly synthesized Ni NPs were confirmed by several analytical techniques such as UV-Visible spectroscopy (UV-Vis), Fourier Transform Infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Scanning Electron Microscope (SEM), Energy Dispersive X-ray analysis (EDAX), Transmission Electron Microscope (TEM) and Zeta potential. The obtained results infer that green synthesized Ni NPs are in cubical shape with an average particle size of 47nm. Synthesized Ni NPs were subjected to pesticidal activity against agricultural pest Callasobruchus maculates (C. maculates) which resulted in 97.31% mortality. These results were compared with commercially available standard Azadirachtin. Also we have studied larvicidal activity against Aedes ageypti (A. ageypti) larvae which resulted in LC 50 and LC 90 value of 259.24, 446.99ppm respectively and the result proved to be significant which were processed by ANOVA LSD Tukey's test. PMID- 27371916 TI - Determination of the threshold dose distribution in photodynamic action from in vitro experiments. AB - The concept of threshold in photodynamic action on cells or microorganisms is well observed in experiments but not fully explored on in vitro experiments. The intercomparison between light and used photosensitizer among many experiments is also poorly evaluated. In this report, we present an analytical model that allows extracting from the survival rate experiments the data of the threshold dose distribution, ie, the distribution of energies and photosensitizer concentration necessary to produce death of cells. Then, we use this model to investigate photodynamic therapy (PDT) data previously published in literature. The concept of threshold dose distribution instead of "single value of threshold" is a rich concept for the comparison of photodynamic action in different situations, allowing analyses of its efficiency as well as determination of optimized conditions for PDT. We observed that, in general, as it becomes more difficult to kill a population, the distribution tends to broaden, which means it presents a large spectrum of threshold values within the same cell type population. From the distribution parameters (center peak and full width), we also observed a clear distinction among cell types regarding their response to PDT that can be quantified. Comparing data obtained from the same cell line and used photosensitizer (PS), where the only distinct condition was the light source's wavelength, we found that the differences on the distribution parameters were comparable to the differences on the PS absorption. At last, we observed evidence that the threshold dose distribution matches the curve of apoptotic activity for some PSs. PMID- 27371917 TI - The challenges of including impacts on biodiversity in agricultural life cycle assessments. AB - Agriculture is considered to be one of the main drivers for worldwide biodiversity loss but the impacts of agricultural production on biodiversity have not been extensively considered in Life Cycle Assessments (LCAs). Recent realisation that biodiversity impact should be included in comprehensive LCAs has led to attempts to develop and implement methods for biodiversity impact assessment. In this review, twenty-two different biodiversity impact assessment methods have been analysed to identify their strengths and weaknesses in terms of their comprehensiveness in the evaluation of agricultural products. Different criteria, which had to meet the specific requirements of biodiversity research, life cycle assessment methodology, and the evaluation of agricultural products, were selected to investigate the identified methods. Very few of the methods were developed with the specific intention of being used for agricultural LCAs. Furthermore, none of the methods can be applied globally while at the same time being able to differentiate between various agricultural intensities. Global value chains and the increasing awareness of different biodiversity impacts of agricultural production systems demand the development of evaluation methods that are able to overcome these shortcomings. Despite the progress that has already been achieved, there are still unresolved difficulties which need further research and improvement. PMID- 27371919 TI - Walking impairs cognitive performance among people with multiple sclerosis but not controls. AB - People with multiple sclerosis (MS) complain of problems completing two tasks simultaneously; sometimes called 'dual-tasking' (DT). Previous research in DT among people with MS has focused on how adding a cognitive task interferes with gait and few have measured how adding a motor task could interfere with cognition. We aimed to determine the extent to which walking affects a concurrent working memory task in people with MS compared to healthy controls. We recruited MS participants (n=13) and controls (n=10) matched by age (+/-3years), education (+/-3years) and gender. Participants first completed the cognitive task (subtracting 7's from the previous number) and then again while walking on an instrumented walkway. Although there were no baseline differences in cognition or walking between MS participants and controls, MS participants demonstrated a 52% decrease in number of correct answers during DT (p<0.001). Mental Tracking Rate (% correct answers/min) correlated strongly with MS-related disability measured using the Expanded Disability Status Scale (EDSS; r(11)=-0.68, p<0.01). We propose that compromised mental tracking during walking could be related to limited neural resource capacity and could be a potentially useful outcome measure to detect ecologically valid dual tasking impairments. PMID- 27371918 TI - Laterality of repetitive finger movement performance and clinical features of Parkinson's disease. AB - Impairments in acoustically cued repetitive finger movement often emerge at rates near to and above 2Hz in persons with Parkinson's Disease (PD) in which some patients move faster (hastening) and others move slower (bradykinetic). The clinical features impacting this differential performance of repetitive finger movement remain unknown. The purpose of this study was to compare repetitive finger movement performance between the more and less affected side, and the difference in clinical ratings among performance groups. Forty-one participants diagnosed with idiopathic PD completed an acoustically cued repetitive finger movement task while "on" medication. Eighteen participants moved faster, 10 moved slower, and 13 were able to maintain the appropriate rate at rates above 2Hz. Clinical measures of laterality, disease severity, and the UPDRS were obtained. There were no significant differences between the more and less affected sides regardless of performance group. Comparison of disease severity, tremor, and rigidity among performance groups revealed no significant differences. Comparison of posture and postural instability scores revealed that the participants that demonstrated hastening had worse posture and postural instability scores. Consideration of movement rate during the clinical evaluation of repetitive finger movement may provide additional insight into varying disease features in persons with PD. PMID- 27371920 TI - Metabonomic identification of the effects of the Zhimu-Baihe saponins on a chronic unpredictable mild stress-induced rat model of depression. AB - The herbal pair Zhimu-Baihe (Zhimu: Anemarrhena asphodeloides; Baihe: Lilium brownii var. viridulum) is a traditional Chinese medicament used for the treatment of depression. However, the relevant mechanisms of action has not been clarified. This study investigated the anti-depressant activity of the total saponins from Zhimu and Baihe and the mechanisms underlying using a chronic unpredictable mild stress (CUMS)-induced rat model of depression. High performance liquid chromatography with electrochemical detection (HPLC-ECD) was applied to determine the levels of three monoamine neurotransmitters, 5 hydroxytryptamine (5-HT), noradrenaline (NE) and dopamine (DA), in the rat hippocampus. Optimized pretreatment of samples and mass spectrometry conditions were used to analyse the metabonomic profile of the hippocampus. The 5-HT and NE levels in the CUMS group were reduced compared with the control group, whereas all groups had similar DA levels. The metabonomic profile of the hippocampus revealed 32 differential metabolites between the CUMS and control group, among which 18 metabolites were significantly recovered in the Anemarrhena saponins and Lilium saponins (AL) combination intervention group. These results suggested an anti-depressant effect of AL. Moreover, 24 metabolites in AL group were better recovered compared with the Anemarrhena saponins (AS) or Lilium saponins (LS) intervention groups, suggesting a synergetic effect of AS and LS in the treatment of depression. The anti-depressant effect might be related to the regulation of several metabolic pathways, including monoamine neurotransmitter synthesis (especially 5-HT and NE), and amino acid, fatty acid, and phospholipid metabolism in rats. PMID- 27371921 TI - Quantitative assay of photoinduced DNA strand breaks by real-time PCR. AB - Real-time PCR (qPCR) - a modern methodology primarily used for studying gene expression has been employed for the quantitative assay of an important class of DNA damage - single strand breaks. These DNA lesions which may lead to highly cytotoxic double strand breaks were quantified in a model system where double stranded DNA was sensitized to UV photons by labeling with 5-bromo-2' deoxyuridine. The amount of breaks formed due to irradiation with several doses of 320nm photons was assayed by two independent methods: LC-MS and qPCR. A very good agreement between the relative damage measured by the two completely different analytical tools proves the applicability of qPCR for the quantitative analysis of SSBs. Our results suggest that the popularity of the hitherto underestimated though accurate and site-specific technique of real-time PCR may increase in future DNA damage studies. PMID- 27371922 TI - Novel (2,6-difluorophenyl)(2-(phenylamino)pyrimidin-4-yl)methanones with restricted conformation as potent non-nucleoside reverse transcriptase inhibitors against HIV-1. AB - To elucidate the structure-geometry-activity relationship in diarylpyrimidine family (DAPYs) containing carbonyl linker between the central pyrimidine core and phenyl type B-arm, a series of (2,6-difluorophenyl)(2-(phenylamino)pyrimidin-4 yl)methanones was designed, prepared and tested for their anti-HIV-1 activity. The carbonyl linker bearing B phenyl arm was successfully attached at both C-2 and C-4 positions of the central pyrimidine ring using a new synthetic approach. Further modifications of target compounds are present at C-5 position of the pyrimidine ring. In vitro anti-HIV-1 activity study performed on a series of 22 compounds confirmed the crucial importance of both conformational rigidity between phenyl B arm and the pyrimidine core linked through the carbonyl bridge, as well as presence of fluoro substituents in ortho-positions of phenyl B moiety. The most potent derivative of the series, compound 17, having almost perpendicular angle within the two planes made from the B aromatic arm and the pyrimidine ring, exhibited low nanomolar anti-HIV-1 activity (EC50 = 4 nM) with no significant toxicity (CC50 > 57.1 MUM). PMID- 27371923 TI - Syntheses of new 3-thiazolyl coumarin derivatives, in vitro alpha-glucosidase inhibitory activity, and molecular modeling studies. AB - 3-Thiazolylcoumarin derivatives 1-14 were synthesized via one-pot two step reactions, and screened for in vitro alpha-glucosidase inhibitory activity. All compounds showed inhibitory activity in the range of IC50 = 0.12 +/- 0.01-16.20 +/- 0.23 MUM as compared to standard acarbose (IC50 = 38.25 +/- 0.12 MUM), and also found to be nontoxic. Molecular docking study was carried out in order to establish the structure-activity relationship (SAR) which demonstrated that electron rich centers at one and electron withdrawing centers at the other end of the molecules showed strong inhibitory activity. All the synthesized compounds were characterized by spectroscopic techniques such as EI-MS, HREI-MS, (1)H NMR and (13)C NMR. CHN analysis was also performed. PMID- 27371924 TI - Design, synthesis and biological evaluation of berberine-benzimidazole hybrids as new type of potentially DNA-targeting antimicrobial agents. AB - A series of novel berberine-benzimidazole derivatives were conveniently and efficiently synthesized and characterized by NMR, IR, MS and HRMS spectra. Most of the prepared compounds showed effective antimicrobial activities in contrast with clinical norfloxacin, chloromycin and fluconazole. Especially, compound 5d exhibited good anti-MRSA, anti-Escherichia coli, and anti-Salmonella typhi activity with low MIC values of 2-8 MUg/mL, which were comparable or even superior to reference drugs. The preliminarily interactive investigation revealed that the most active compound 5d could effectively intercalate into DNA to form 5d-DNA complex and cleavage DNA by agarose gel electrophoresis experiments. It was also found that compound 5d was able to efficiently permeabilize the membranes of both Gram-positive (MRSA) and Gram-negative (E. coli DH52) bacteria. Experiments and molecular docking both showed that human serum albumin (HSA) could effectively transport compound 5d and hydrophobic interactions and hydrogen bonds play important roles in the association of compound 5d with HSA. PMID- 27371925 TI - Engineering another class of anti-tubercular lead: Hit to lead optimization of an intriguing class of gyrase ATPase inhibitors. AB - A structure based medium throughput virtual screening campaign of BITS-Pilani in house chemical library to identify novel binders of Mycobacterium tuberculosis gyrase ATPase domain led to the discovery of a quinoline scaffold. Further medicinal chemistry explorations on the right hand core of the early hit, engendered a potent lead demonstrating superior efficacy both in the enzyme and whole cell screening assay. The binding affinity shown at the enzyme level was further corroborated by biophysical characterization techniques. Early pharmacokinetic evaluation of the optimized analogue was encouraging and provides interesting potential for further optimization. PMID- 27371926 TI - Synthesis of a series of novel dihydroartemisinin monomers and dimers containing chalcone as a linker and their anticancer activity. AB - A new series of monomer and dimer derivatives of dihydroartemisinin (DHA) containing substituted chalcones as a linker were synthesized and investigated for their cytotoxicity in human cancer cell lines HL-60 (leukemia), Mia PaCa-2 (pancreatic cancer), PC-3 (prostate cancer), LS180 (colon cancer) and HEPG2 (hepatocellular carcinoma). Some of these derivatives have greater antiproliferative and cytotoxic effects in tested cell lines than parent compound DHA. The structures of the all compounds were confirmed by IR, (1)H NMR and mass spectral data. Among the new derivatives, compounds 8, 14, 15, 20 and 24 were found to be more active than parent DHA against tested human cancer cell lines. DHA derivatives were found to be most active in human leukemia cell lines with compounds 8, 14, 15, 20 and 24 showed IC50 values less than 1 MUM for 48 h whereas DHA has IC50 value of 2 MUM at same time period. The most potent compounds 8 with IC50 = 0.3 MUM (at par with doxorubicin (IC50 = 0.3 MUM)) and 15 with IC50 = 0.4 MUM, of the series, six and three times active than DHA (with IC50 = 2 MUM) respectively were selected for further mechanistic work in human leukemia HL-60 cells. PMID- 27371927 TI - Design, synthesis, and anti-proliferative activity of 1-(4-methoxyphenyl)-12 hydroxymethyl-p-carborane derivatives. AB - 1-(4-Methoxyphenyl)-12-hydroxymethyl-p-carborane (2a), which is a precursor to the previously developed potent carborane-containing ER agonist BE120, exhibited weak cell growth inhibitory activity against four human cancer cell lines (MCF-7, MDA-MB-453, LNCaP, and PC-3). The biological evaluation of a series of derivatives of 2a revealed that an increased number of methoxy groups on the benzene ring of 2a enhanced the cell growth inhibitory activity. Trimethoxyphenyl derivative 2g afforded the most potent cell growth inhibitory activity (mean GI50 value: 5.8 MUM) in a panel screening using 39 human cancer cell lines. Moreover, 2g induced for MDA-MB-453 breast cancer cell lines an arrest of the cell cycle in the G2/M phase and apoptosis mediated by caspase-3/7. PMID- 27371928 TI - Does nitrate co-pollution affect biological responses of an aquatic plant to two common herbicides? AB - Aquatic systems in agricultural landscapes are subjected to multiple stressors, among them pesticide and nitrate run-off, but effects of both together have rarely been studied. We investigated possible stress-specific and interaction effects using the new OECD test organism, Myriophyllum spicatum, a widespread aquatic plant. In a fully factorial design, we used two widely applied herbicides, isoproturon and mesosulfuron-methyl, in concentration-response curves at two nitrate levels (219.63 and 878.52mg N-NO3). We applied different endpoints reflecting plant performance such as growth, pigment content, content in phenolic compounds, and plant stoichiometry. Relative growth rates based on length (RGR-L) were affected strongly by both herbicides, while effects on relative growth rate based on dry weight (RGR-DW) were apparent for isoproturon but hardly visible for mesosulfuron-methyl due to an increase in dry matter content. The higher nitrate level further reduced growth rates, specifically with mesosulfuron-methyl. Effects were visible between 50 and 500MUgL(-1) for isoproturon and 0.5-5MUgL(-1) for mesosulfuron-methyl, with some differences between endpoints. The two herbicides had opposite effects on chlorophyll, carotenoid and nitrogen contents in plants, with values increasing with increasing concentrations of isoproturon and decreasing for mesosulfuron-methyl. Herbicides and nitrate level exhibited distinct effects on the content in phenolic compounds, with higher nitrate levels reducing total phenolic compounds in controls and with isoproturon, but not with mesosulfuron-methyl. Increasing concentrations of mesosulfuron-methyl lead to a decline of total phenolic compounds, while isoproturon had little effect. Contents of carbon, nitrogen and phosphorus changed depending on the stressor combination. We observed higher phosphorus levels in plants exposed to certain concentrations of herbicides, potentially indicating a metabolic response. The C:N molar ratio decreased strongly with isoproturon and increased with mesosulfuron-methyl. The C:P and N:P ratios did not vary for most herbicide concentrations, indicating homeostasis. Nitrate level had no effect on the C:N ratio, but the N:P ratio increased in high nitrate level treatments, indicating that the former is more strictly regulated by the plant than the latter. We conclude that the multi-stress impacts caused to aquatic primary producers by herbicides and nitrate enrichment, as often observed in agricultural run-off, not only affected growth and pigment content, but also structural traits (dry matter content) and other physiological traits (elemental stoichiometry, phenolic compounds). Changes in those might have indirect effects on biotic interactions and elemental cycles. We suggest considering some of these endpoints in future studies in environmental risk assessment for agricultural run-off. PMID- 27371929 TI - The short-term association of road traffic noise with cardiovascular, respiratory, and diabetes-related mortality. AB - BACKGROUND: Road traffic noise has well-documented effects on cardiovascular, respiratory, and metabolic health. Numerous studies have reported long-term associations of urban noise with some diseases and outcomes, including death. However, to date there are no studies on the short-term association between this pollutant and a set of various specific causes of death. OBJECTIVES: To investigate the short-term association of road traffic noise with daily cause specific mortality. METHODS: We used a time-stratified case-crossover design with Poisson regression. Predictor variables were daytime, nighttime, and 24-h equivalent noise levels, and maximum daytime and nighttime noise levels. Outcome variables were daily death counts for various specific causes, stratifying by age. We adjusted for primary air pollutants (PM2.5 and NO2) and weather conditions (mean temperature and relative humidity). RESULTS: In the >=65 age group, increased mortality rates per 1 dBA increase in maximum nocturnal noise levels at lag 0 or 1 day were 2.9% (95% CI 1.0, 4.8%), 3.5% (95% CI 1.1, 6.1%), 2.4% (95% CI 0.1, 4.8%), 3.0% (95% CI 0.2, 5.8%), and 4.0% (95% CI 1.0, 7.0%), for ischemic heart disease, myocardial infarction, cerebrovascular disease, pneumonia, and COPD, respectively. For diabetes, 1 dBA increase in equivalent nocturnal noise levels at lag 1 was associated with an increased mortality rate of 11% (95% CI 4.0, 19%). In the <65 age group, increased mortality rates per 1 dBA increase in equivalent nocturnal noise levels at lag 0 were 11% (95% CI 4.2, 18%) and 11% (95% CI 4.2, 19%) for ischemic heart disease and myocardial infarction, respectively. CONCLUSION: Road traffic noise increases the short-term risk of death from specific diseases of the cardiovascular, respiratory, and metabolic systems. PMID- 27371930 TI - Cardiovascular and stress responses to short-term noise exposures-A panel study in healthy males. AB - BACKGROUND: While previous epidemiological studies report adverse effects of long term noise exposure on cardiovascular health, the mechanisms responsible for these effects are unclear. We sought to elucidate the cardiovascular and stress response to short-term, low (31.5-125Hz) and high (500-2000Hz) frequency noise exposures. METHODS: Healthy male (n=10) participants were monitored on multiple visits during no noise, low- or high-frequency noise exposure scenarios lasting 40min. Participants were fitted with an ambulatory electrocardiogram (ECG) and blood pressure measures and saliva samples were taken before, during and after noise exposures. ECGs were processed for measures of heart rate variability (HRV): high-frequency power (HF), low-frequency power (LF), the root of the mean squared difference between adjacent normal heart beats (N-N) intervals (RMSSD), and the standard deviation of N-N intervals (SDNN). Systolic blood pressure (SBP), diastolic blood pressure (DPB), and pulse were reported and saliva was analyzed for salivary cortisol and amylase. Multivariate mixed-effects linear regression models adjusted for age were used to identify statistically significant difference in outcomes by no noise, during noise or after noise exposure periods and whether this differed by noise frequency. RESULTS: A total of 658, 205, and 122, HRV, saliva, and blood pressure measurements were performed over 41 person days. Reductions in HRV (LF and RMSSD) were observed during noise exposure (a reduction of 19% (-35,-3.5) and 9.1% (-17,-1.1), respectively). After adjusting for noise frequency, during low frequency noise exposure, HF, LF, and SDNN were reduced (a reduction of 32% (-57,-6.2), 34% (-52,-15), and 16% (-26, 6.1), respectively) and during high frequency noise exposure, a 21% (-39,-2.3) reduction in LF, as compared to during no noise exposure, was found. No significant (p<0.05) changes in blood pressure, salivary cortisol, or amylase were observed. CONCLUSIONS: These results suggest that exposure to noise, and in particular, to low-frequency noise, negatively impacts HRV. The frequencies of noise should be considered when evaluating the cardiovascular health impacts of exposure. PMID- 27371931 TI - Freeze desalination of seawater using LNG cold energy. AB - With the aid of cold energy from regasification of liquefied natural gas (LNG), freeze desalination (FD) is an emerging technology for seawater desalination because of its low energy characteristics and insensitivities to fouling problems. This work aims to investigate the major operating parameters of FD such as coolant temperature, freezing duration, supercooling, seeding, agitation, crystallizer material and subsequent washing procedure on ice production and water quality. It was found that the optimal freezing duration per batch was 1 h for an iron crystallizer and 1.5 h for a glass crystallizer. The optimal coolant temperature should be around -8 degrees C. The optimal amount of washing water to clean the raw ice was about 50 wt% of the raw ice. Over 50 wt% of the feed could be recovered as raw ice within 1 h, which means an overall ice recovery rate of higher than 25% (of the original seawater), considering the consumption of washing water. Both artificial and real seawater were tested under the optimized conditions. The total dissolved solid in the product ice was around 300 ppm, which met the World Health Organization (WHO) potable water salinity standard of 500 ppm. Therefore, the process parameters optimized in this study can be directly used for the freeze desalination of seawater. PMID- 27371932 TI - Prediction of three-dimensional structures and structural flexibilities of wild type and mutant cytochrome P450 1A2 using molecular dynamics simulations. AB - In this study, we investigated the effect of genetic polymorphism on the three dimensional (3D) conformation of cytochrome P450 1A2 (CYP1A2) using molecular dynamics (MD) simulations. CYP1A2, a major drug-metabolizing enzyme among cytochrome P450 enzymes (CYPs), is known to have many variant alleles. The genetic polymorphism of CYP1A2 may cause individual differences in the pharmacokinetics of medicines. By performing 100ns or longer MD simulations, we investigated the influence of amino acid mutation on the 3D structures and the dynamic properties of proteins. The results show that the static structures were changed by the mutations of amino acid residues, not only near the mutated residues but also in distant portions of the proteins. Moreover, the mutation of only one amino acid was shown to change the structural flexibility of proteins, which may influence the substrate recognition and enzymatic activity. Our results clearly suggest that it is necessary to investigate the dynamic property as well as the static 3D structure for understanding the change of the enzymatic activity of mutant CYP1A2. PMID- 27371933 TI - Binding mechanism of CDK5 with roscovitine derivatives based on molecular dynamics simulations and MM/PBSA methods. AB - Roscovitine derivatives are potent inhibitors of cyclin-dependent kinase 5 (CDK5), but they exhibit different activities, which has not been understood clearly up to now. On the other hand, the task of drug design is difficult because of the fuzzy binding mechanism. In this context, the methods of molecular docking, molecular dynamics (MD) simulation, and binding free energy analysis are applied to investigate and reveal the detailed binding mechanism of four roscovitine derivatives with CDK5. The electrostatic and van der Waals interactions of the four inhibitors with CDK5 are analyzed and discussed. The calculated binding free energies in terms of MM-PBSA method are consistent with experimental ranking of inhibitor effectiveness for the four inhibitors. The hydrogen bonds of the inhibitors with Cys83 and Lys33 can stabilize the inhibitors in binding sites. The van der Waals interactions, especially the pivotal contacts with Ile10 and Leu133 have larger contributions to the binding free energy and play critical roles in distinguishing the variant bioactivity of four inhibitors. In terms of binding mechanism of the four inhibitors with CDK5 and energy contribution of fragments of each inhibitor, two new CDK5 inhibitors are designed and have stronger inhibitory potency. PMID- 27371934 TI - 1 H and 13 C NMR spectral assignments of novel adamantyl and di-adamantyl derivatives of 1,2-dihydroxynaphthalenes, 1,8-dihydroxynaphthalenes, 2,3 dihydroxynaphthalenes, 2,6-dihydroxynaphthalenes and 2,7-dihydroxynaphthalenes. PMID- 27371935 TI - Long-term follow-up after endovascular treatment of hepatic venous outflow obstruction following liver transplantation. AB - Hepatic venous outflow obstruction (HVOO) is a rare complication after liver transplantation (LT) associated with significant morbidity and reduced graft survival. Endovascular intervention has become the first-line treatment for HVOO, but data on long-term outcomes are lacking. We have analysed outcomes after endovascular intervention for HVOO in 905 consecutive patients who received 965 full-size LT at our unit from January 2007 to June 2014. There were 27 (3%) patients who underwent hepatic venogram for suspected HVOO, with persistent ascites being the most common symptom triggering the investigation (n = 19, 70%). Of those, only 10 patients demonstrated either stricture or pressure gradient over 10 mmHg on venogram, which represents a 1% incidence of HVOO. The endovascular interventions were balloon dilatation (n = 3), hepatic vein stenting (n = 4) and stenting with dilatation (n = 3). Two patients required restenting due to stent migration. The symptoms of HVOO completely resolved in all but one patient, with a median follow-up period of 74 (interquartile range 39-89) months. There were no procedure-related complications or mortality. In conclusion, the incidence of HVOO in patients receiving full-size LT is currently very low. Endovascular intervention is an effective and safe procedure providing symptom relief with long-lasting primary patency. PMID- 27371936 TI - The role of oxidative stress in organophosphate and nerve agent toxicity. AB - Organophosphate (OP) nerve agents exert their toxicity through inhibition of acetylcholinesterase. The excessive stimulation of cholinergic receptors rapidly causes neuronal damage, seizures, death, and long-term neurological impairment in those that survive. Owing to the lethality of organophosphorus agents and the growing risk they pose, medical interventions that prevent OP toxicity and the delayed injury response are much needed. Studies have shown that oxidative stress occurs in models of subacute, acute, and chronic exposure to OP agents. Key findings of these studies include alterations in mitochondrial function and increased free radical-mediated injury, such as lipid peroxidation. This review focuses on the role of reactive oxygen species in OP neurotoxicity and its dependence on seizure activity. Understanding the sources, mechanisms, and pathological consequences of OP-induced oxidative stress can lead to the development of rational therapies for treating toxic exposures. PMID- 27371937 TI - Savanna woody encroachment is widespread across three continents. AB - Tropical savannas are a globally extensive biome prone to rapid vegetation change in response to changing environmental conditions. Via a meta-analysis, we quantified savanna woody vegetation change spanning the last century. We found a global trend of woody encroachment that was established prior the 1980s. However, there is critical regional variation in the magnitude of encroachment. Woody cover is increasing most rapidly in the remaining uncleared savannas of South America, most likely due to fire suppression and land fragmentation. In contrast, Australia has experienced low rates of encroachment. When accounting for land use, African savannas have a mean rate annual woody cover increase two and a half times that of Australian savannas. In Africa, encroachment occurs across multiple land uses and is accelerating over time. In Africa and Australia, rising atmospheric CO2 , changing land management and rainfall are likely causes. We argue that the functional traits of each woody flora, specifically the N-fixing ability and architecture of woody plants, are critical to predicting encroachment over the next century and that African savannas are at high risk of widespread vegetation change. PMID- 27371938 TI - Predictors and Outcomes of Psychiatric Hospitalization in Youth Presenting to the Emergency Department with Suicidality. AB - Youth suicide attempters presenting to the emergency department (ED) are frequently admitted to psychiatric inpatient hospitals, yet little is known about how clinicians decide which youths to admit versus discharge to outpatient care. We examine predictors of inpatient hospitalization and describe service use outcomes associated with hospitalization in 181 youths drawn from consecutive ED admissions for suicidality. Predictors of hospitalization include ED site, suicide plan, and parent report of problems. Hospitalization was associated with improved linkage to outpatient treatment and more intensive service use. Future research is needed to understand the best service delivery and treatments for these high-risk youth. PMID- 27371939 TI - Heat resistance throughout ontogeny: body size constrains thermal tolerance. AB - Heat tolerance is a trait of paramount ecological importance and may determine a species' ability to cope with ongoing climate change. Although critical thermal limits have consequently received substantial attention in recent years, their potential variation throughout ontogeny remained largely neglected. We investigate whether such neglect may bias conclusions regarding a species' sensitivity to climate change. Using a tropical butterfly, we found that developmental stages clearly differed in heat tolerance. It was highest in pupae followed by larvae, adults and finally eggs and hatchlings. Strikingly, most of the variation found in thermal tolerance was explained by differences in body mass, which may thus impose a severe constraint on adaptive variation in stress tolerance. Furthermore, temperature acclimation was beneficial by increasing heat knock-down time and therefore immediate survival under heat stress, but it affected reproduction negatively. Extreme temperatures strongly reduced survival and subsequent reproductive success even in our highly plastic model organism, exemplifying the potentially dramatic impact of extreme weather events on biodiversity. We argue that predictions regarding a species' fate under changing environmental conditions should consider variation in thermal tolerance throughout ontogeny, variation in body mass and acclimation responses as important predictors of stress tolerance. PMID- 27371940 TI - An Interpretive Phenomenological Inquiry of Family and Friend Reactions to Suicide Disclosure. AB - Suicide attempt survivors' interpretations of reactions to attempts are understudied, yet could inform prevention efforts concerning subsequent attempts. Interviews with 40 attempt survivors about family and friend reactions were analyzed using interpretive phenomenological techniques. Three distinct patterns emerged as follows: (a) Stigmatizing statements and emphasis on reactor's feelings were interpreted as signs that attempt survivors were a burden to others, (b) avoidant reactions and excessive monitoring were interpreted as cues that suicidal behavior must remain hidden to not be a burden, and (c) asking questions and projecting strength were interpreted as signs that attempt survivors belonged and were not a burden. These findings highlight the importance of working with family and friends to encourage reactions that reduce the risk of future attempts. PMID- 27371941 TI - Limitations in current acetylcholinesterase structure-based design of oxime antidotes for organophosphate poisoning. AB - Acetylcholinesterase (AChE; EC 3.1.1.7), an essential enzyme of cholinergic neurotransmission in vertebrates, is a primary target in acute nerve agent and organophosphate (OP) pesticide intoxication. Catalytically inactive OP-AChE conjugates formed between the active-center serine and phosphorus of OPs can, in principle, be reactivated by nucleophilic oxime antidotes. Antidote efficacy is limited by the structural diversity of OP-AChE conjugates resulting from differences in the structure of the conjugated OP, the different active-center volumes they occupy when conjugated to the active-center serine of AChE, and the distinct chemical characteristics of both OPs and oximes documented in numerous X ray structures of OP-conjugated AChEs. Efforts to improve oxime reactivation efficacy by AChE structure-based enhancement of oxime structure have yielded only limited success. We outline here the potential limitations of available AChE X ray structures that preclude an accurate prediction of oxime structures, which are necessary for association in the OP-AChE gorge and nucleophilic attack of the OP-conjugated phosphorus. PMID- 27371942 TI - Impact of ART on the fertility of HIV-positive women in sub-Saharan Africa. AB - OBJECTIVE: Understanding the fertility of HIV-positive women is critical to estimating HIV epidemic trends from surveillance data and to planning resource needs and coverage of prevention of mother-to-child transmission services in sub Saharan Africa. In the light of the considerable scale-up in antiretroviral therapy (ART) coverage over the last decade, we conducted a systematic review of the impact of ART on the fertility outcomes of HIV-positive women. METHODS: We searched Medline, Embase, Popline, PubMed and African Index Medicus. Studies were included if they were conducted in sub-Saharan Africa and provided estimates of fertility outcomes (live births or pregnancies) among women on ART relative to a comparison group. RESULTS: Of 2070 unique references, 18 published papers met all eligibility criteria. Comparisons fell into four categories: fertility of HIV positive women relative to HIV-negative women; fertility of HIV-positive women on ART compared to those not yet on ART; fertility differences by duration on ART; and temporal trends in fertility among HIV-positive women. Evidence indicates that fertility increases after approximately the first year on ART and that while the fertility deficit of HIV-positive women is shrinking, their fertility remains below that of HIV-negative women. These findings, however, were based on limited data mostly during the period 2005-2010 when ART scaled up. CONCLUSIONS: Existing data are insufficient to characterise how ART has affected the fertility of HIV positive women in sub-Saharan Africa. Improving evidence about fertility among women on ART is an urgent priority for planning HIV resource needs and understanding HIV epidemic trends. Alternative data sources such as antenatal clinic data, general population cohorts and population-based surveys can be harnessed to understand the issue. PMID- 27371943 TI - Positive and Negative Expectations of Hopelessness as Longitudinal Predictors of Depression, Suicidal Ideation, and Suicidal Behavior in High-Risk Adolescents. AB - The relationship between hopelessness and depression in predicting suicide related outcomes varies based on the anticipation of positive versus negative events. In this prospective study of adolescents at elevated risk for suicide, we used two Beck Hopelessness Scale subscales to assess the impact of positive and negative expectations in predicting depression, suicidal ideation, and suicidal behavior over a 2- to 4-year period. In multivariate regressions controlling for depression, suicidal ideation, and negative-expectation hopelessness, positive expectation hopelessness was the only significant predictor of depressive symptoms and suicidal behavior. Clinical interventions may benefit from bolstering positive expectations and building optimism. PMID- 27371944 TI - Midterm Outcomes of the Nellix Endovascular Aneurysm Sealing System: A Dual Center Experience. AB - PURPOSE: To report midterm outcomes of the Nellix Endovascular Aneurysm Sealing (EVAS) System in the treatment of abdominal aortic aneurysm (AAA). METHODS: Between September 2013 and July 2014, 64 AAA patients (mean age 76.6+/-6.8 years; 61 men) were treated with the EVAS system at 2 centers (only procedures performed at least 12 months prior to the analysis were included). Most patients were treated for a stable AAA, while 1 patient was treated for a ruptured aneurysm. Mean aneurysm diameter was 57.3+/-9.3 mm. The proximal neck measured a mean 21.5+/-3.3 mm in diameter and 27.0+/-12.1 mm long; the neck angle was 16.9 degrees +/-19.3 degrees . Eleven (17.2%) patients were treated outside the instructions for use (IFU). RESULTS: Technical success was achieved in 63 (98.4%) of 64 patients; 1 type Ia endoleak was treated intraoperatively. One (1.6%) aneurysm-related death occurred at 4 months due to a secondary aortoenteric fistula. Overall, endoleaks occurred in 3 (4.7%) patients (2 type Ia, 1 type II). The estimated rates for 18-month overall survival, freedom from aneurysm-related death, and freedom from secondary interventions were 92.7%, 98.4%, and 95.0%, respectively. Patients treated outside the IFU had a significantly higher incidence of device-related complications (p=0.03). CONCLUSION: The use of the Nellix device in everyday clinical practice is safe and offers promising midterm results. The risk of secondary aortoenteric fistula requires further analysis. Longer follow-up is needed to assess the actual efficacy of the device, although the risk of migration with late endoleak seems low. PMID- 27371945 TI - A novel drug management system in the Febuxostat versus Allopurinol Streamlined Trial: A description of a pharmacy system designed to supply medications directly to patients within a prospective multicenter randomised clinical trial. AB - BACKGROUND: Trials of investigational medicinal products are required to adhere to strict guidelines with regard to the handling and supply of medication. Information technology offers opportunities to approach clinical trial methodology in new ways. This report summarises a novel pharmacy system designed to supply trial medications directly to patients by post in the Febuxostat versus Allopurinol Streamlined Trial. METHOD: A bespoke web-based software package was designed to facilitate the direct supply of trial medications to Febuxostat versus Allopurinol Streamlined Trial participants from a pharmacy based in the Medicines Monitoring Unit, University of Dundee. RESULTS: To date, 65,467 packs of medication have been dispensed using the system to 3978 patients. Up to 238 packs per day have been dispensed. CONCLUSION: The Medicines Monitoring Unit Febuxostat versus Allopurinol Streamlined Trial drug management system is an effective method of administering the complex drug supply requirements of a large scale clinical trial with advantages over existing arrangements. A low rate of loss to follow-up in the Febuxostat versus Allopurinol Streamlined Trial may be attributable to the drug management system. PMID- 27371946 TI - Identification of Cargo for Adaptor Protein (AP) Complexes 3 and 4 by Sucrose Gradient Profiling. AB - Intracellular vesicle trafficking is a fundamental process in eukaryotic cells. It enables cellular polarity and exchange of proteins between subcellular compartments such as the plasma membrane or the vacuole. Adaptor protein complexes participate in the vesicle formation by specific selection of the transported cargo. We investigated the role of the adaptor protein complex 3 (AP 3) and adaptor protein complex 4 (AP-4) in this selection process by screening for AP-3 and AP-4 dependent cargo proteins. Specific cargo proteins are expected to be mis-targeted in knock-out mutants of adaptor protein complex components. Thus, we screened for altered distribution profiles across a density gradient of membrane proteins in wild type versus ap-3beta and ap-4beta knock-out mutants. In ap-3beta mutants, especially proteins with transport functions, such as aquaporins and plasma membrane ATPase, as well as vesicle trafficking proteins showed differential protein distribution profiles across the density gradient. In the ap-4beta mutant aquaporins but also proteins from lipid metabolism were differentially distributed. These proteins also showed differential phosphorylation patterns in ap-3beta and ap-4beta compared with wild type. Other proteins, such as receptor kinases were depleted from the AP-3 mutant membrane system, possibly because of degradation after mis-targeting. In AP-4 mutants, membrane fractions were depleted for cytochrome P450 proteins, cell wall proteins and receptor kinases. Analysis of water transport capacity in wild type and mutant mesophyll cells confirmed aquaporins as cargo proteins of AP-3 and AP-4. The combination of organelle density gradients with proteome analysis turned out as a suitable experimental strategy for large-scale analyses of protein trafficking. PMID- 27371948 TI - Mortality and cancer incidence at a fire training college. AB - BACKGROUND: An investigation into concerns about possible health effects of fire training practices at an Australian training facility recommended a study to investigate the risk of cancer and mortality of those with risk of chronic occupational exposure to several chemicals. AIMS: To investigate mortality and cancer incidence in firefighters at the Country Fire Authority (CFA) Fiskville training facility, Victoria, Australia, between 1971 and 1999. METHODS: CFA supplied human resources records, supplemented by self-reported information for a retrospective cohort, and allocated firefighters to low, medium or high groups based on probability of exposure. We linked the cohort to state and national cancer and mortality data. We calculated standardized mortality ratios and standardized cancer incidence ratios (SIRs). RESULTS: The high group (n = 95) had a clearly increased risk of overall cancers SIR = 1.85 (95% CI 1.20-2.73), testicular cancer SIR = 11.9 (1.44-42.9) and melanoma SIR = 4.59 (1.68-9.99) relative to the population of Victoria. Brain cancer was significantly increased for the medium group (n = 256): SIR = 5.74 (1.56-14.7). Mortality was significantly reduced for all groups. CONCLUSIONS: Dealing with supplied records can be problematic but despite the small numbers, we identified an increased risk of cancer for the high group. The mortality data suggested that there was under ascertainment for the medium and low groups which underestimated risk and a possible reporting bias for brain cancer. Small cohorts can still provide statistically significant findings when investigating locations for cancer risk. PMID- 27371947 TI - Dynamics and control of phloem loading of indole-3-acetic acid in seedling cotyledons of Ricinus communis. AB - During seed germination, sugars and auxin are produced from stored precursors or conjugates respectively, and transported to the seedling axis. To elucidate the mode of travel of indole-3-acetic acid (IAA) into the phloem, a solution of [(3)H]IAA, together with [(14)C]sucrose, was injected into the endosperm cavity harboring the cotyledons of germinating seedlings of Ricinus communis Phloem exudate from the cut hypocotyl was collected and the radioactivity recorded. Sucrose loading into the phloem was inhibited at higher IAA levels, and the rate of filling of the transient pool(s) was reduced by IAA. IAA was detected within 10min, with the concentration increasing over 30min and reaching a steady-state by 60min. The kinetics indicated that phloem loading of IAA involving both an active, carrier-based, and a passive, diffusion-based component, with IAA traveling along a pathway containing an intermediary pool, possibly the protoplasts of mesophyll cells. Phloem loading of IAA was altered by sucrose, K(+), and a range of non-specific and IAA-specific analogs and inhibitors in a manner that showed that IAA moves into the phloem from the extra cotyledonary solution by multiple pathways, with a carrier-mediated pathway playing a principal role. PMID- 27371949 TI - Evaluating Patient-Level Medication Regimen Complexity Over Time in Heart Transplant Recipients. AB - BACKGROUND: Medication regimen complexity describes multiple characteristics of a patient's prescribed drug regimen. Heart transplant recipients must comply with a lifelong regimen that consists of numerous medications. However, a systematic assessment of medication regimen complexity over time has not been conducted in this, or any other, transplant population. OBJECTIVE: The objective of this study was to quantify patient-level medication regimen complexity over time following primary heart transplantation and heart retransplantation, using the validated patient-level Medication Regimen Complexity Index (pMRCI) tool. METHODS: Medication lists were reviewed at transplant discharge and years 1, 3, and 5 post primary heart transplant, and at transplant discharge and years 1 and 3 post heart retransplantation. Medications were categorized as transplant-specific, other prescription, and over-the-counter (OTC). RESULTS: In primary heart transplant recipients (n = 60), mean total medication count was 14.3 +/- 3.4 at transplant discharge and did not change significantly over time ( P = 0.64). Transplant-specific medication count decreased significantly from discharge (2.9 +/- 0.4) to year 5 (2.3 +/- 0.6); P = 0.02. However, 32% of patients were taking 16 or more total medications at year 5 posttransplant. More than 70% of the pMRCI score was attributed to other prescription and OTC medications, which was largely driven by dosing frequency in this cohort. Medication complexity did not differ significantly between heart retransplant recipients (n = 11) and matched primary heart transplant controls (n = 22). CONCLUSION: Together, these data highlight the substantial medication burden after heart transplantation and reveal opportunities to address medication regimen complexity in this, and other, transplant populations. PMID- 27371950 TI - Cross-cultural Adaptation and Validation of the Medication Regimen Complexity Index Adapted to Spanish. AB - BACKGROUND: The most widely used validated instrument to assess the complexity of medication regimens is the Medication Regimen Complexity Index (MRCI). OBJECTIVE: This study aimed to translate, adapt, and validate a reliable version of the MRCI adapted to Spanish (MRCI-E). METHODS: The cross-cultural adaptation process consisted of an independent translation by 3 clinical pharmacists and a backtranslation by 2 native English speakers. A reliability analysis was conducted on 20 elderly randomly selected patients. Two clinical pharmacists calculated the MRCI-E from discharge treatments and 2 months later. For the validity analysis, the sample was augmented to 60 patients. Convergent validity was assessed by analyzing the correlation between the number of medications; discriminant validity was stratified by gender; and predictive validity was determined by analyzing the ability to predict readmission and mortality at 3 and 6 months. RESULTS: The MRCI-E retained the original structure of 3 sections. The reliability analysis demonstrated an excellent internal consistency (Cronbach's alpha=0.83), and the intraclass correlation coefficient exceeded 0.9 in all cases. The correlation coefficient with the number of medications was 0.883 ( P<0.001). No significant differences were found when stratified by gender (3.6; 95%CI=-2.9 to 10.2; P=0.27). Patients who were readmitted at 3 months had a higher MRCI-E score (10.7; 95%CI=4.4 to 17.2; P=0.001). The differences remained significant in patients readmitted at 6 months, but differences in mortality were not detected. CONCLUSIONS: The MRCI-E retains the reliability and validity of the original index and provides a suitable tool to assess the complexity of medication regimens in Spanish. PMID- 27371951 TI - Identification of QTLs Associated with Virulence Related Traits and Drug Resistance in Cryptococcus neoformans. AB - Cryptococcus neoformans is a basidiomycete fungus capable of causing deadly meningoenchephilitis, primarily in immunocompromised individuals. Formerly, C. neoformans was composed of two divergent lineages, but these have recently been elevated to species status, now C. neoformans (formerly C. neoformans var. grubii) and C. deneoformans (formerly C. neoformans var. neoformans). While both species can cause deadly infections in humans, C. neoformans is much more prevalent in clinical settings than C. deneoformans However, the genetic factors contributing to their significant differences in virulence remain largely unknown. Quantitative trait locus (QTL) mapping is a powerful tool that can be used to identify genomic regions associated with phenotypic differences between strains. Here, we analyzed a hybrid cross between these two species and identified a total of 23 QTL, including five for melanin production, six for cell size, one for cell wall thickness, five for the frequency of capsule production, three for minimal inhibitory concentration (MIC) of fluconazole in broth, and three for MIC on solid medium. For the fluconazole resistance-associated QTL, three showed environment and/or concentration-specific effects. Our results provide a large number of candidate gene regions from which to explore the molecular bases for phenotypic differences between C. neoformans and C. deneoformans. PMID- 27371952 TI - Scan-o-matic: High-Resolution Microbial Phenomics at a Massive Scale. AB - The capacity to map traits over large cohorts of individuals-phenomics-lags far behind the explosive development in genomics. For microbes, the estimation of growth is the key phenotype because of its link to fitness. We introduce an automated microbial phenomics framework that delivers accurate, precise, and highly resolved growth phenotypes at an unprecedented scale. Advancements were achieved through the introduction of transmissive scanning hardware and software technology, frequent acquisition of exact colony population size measurements, extraction of population growth rates from growth curves, and removal of spatial bias by reference-surface normalization. Our prototype arrangement automatically records and analyzes close to 100,000 growth curves in parallel. We demonstrate the power of the approach by extending and nuancing the known salt-defense biology in baker's yeast. The introduced framework represents a major advance in microbial phenomics by providing high-quality data for extensive cohorts of individuals and generating well-populated and standardized phenomics databases. PMID- 27371953 TI - Simple Test of Manual Dexterity Can Help to Identify Persons at High Risk for Neurodegenerative Diseases in the Community. AB - BACKGROUND: Early identification of individuals at high risk of developing neurodegenerative diseases is essential for timely preventive intervention. However, simple methods that can be used for risk assessment in general practice are lacking. METHODS: Within the population-based Rotterdam Study, we used the Purdue Pegboard Test (PPT) to assess manual dexterity in 4,856 persons (median age 70 years, 58% women) free of parkinsonism and dementia between 2000 and 2004. We followed these persons until January 1, 2012 for the onset of neurodegenerative diseases (defined as first diagnosis of parkinsonism or dementia). We determined the association of PPT scores with incident neurodegenerative disease, adjusting for age, sex, study cohort, level of education, smoking, preferred hand, parental history, memory complaints, and Mini Mental State Examination. Furthermore, we determined the incremental predictive value of PPT, expressed as change in risk classification and discrimination. RESULTS: During follow-up (median 9.2 years), 277 participants were diagnosed with a neurodegenerative disease (227 with dementia and 50 with parkinsonism). Lower PPT scores were associated with higher risk of incident neurodegenerative diseases (hazard ratio [HR] = 1.28, 95% confidence interval [CI]: 1.18-1.41) and improved discrimination of incident neurodegenerative diseases. We also observed significant associations of PPT scores separately with incident dementia (HR = 1.25; 95% CI: 1.14-1.39]) and incident parkinsonism (HR = 1.41; 95% CI: 1.19 1.67). CONCLUSIONS: A rapid, nonlaboratory test of manual dexterity may help to identify persons at high risk for neurodegenerative diseases. This highlights the importance of motor function in the preclinical phase of both dementia and parkinsonism and may aid in selecting individuals for refined screening and neuroprotective trials. PMID- 27371954 TI - Thyroid Status and Mortality Risk in Older Adults With Normal Thyrotropin: Sex Differences in the Milan Geriatrics 75+ Cohort Study. AB - Background: Thresholds of optimal thyroid status in old age are controversial. We investigated the longitudinal association between thyroid parameters and 10-year all-cause mortality risk in older outpatients with normal thyrotropin (TSH) and modification by sex and age. Methods: Baseline TSH, free thyroxine (fT4), and free triiodothyronine (fT3) were assessed in the Milan Geriatrics 75+ Cohort Study. 324 men and 609 women older than 75 years had normal TSH. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for the associations between thyroid parameters and mortality risk using Cox regression. Sex stratified analyses were adjusted for sociodemographic factors and comorbidities. Results: 233 men and 367 women died during follow-up. After adjustment, each 1 mU/L higher TSH was associated with decreased mortality risk in men (HR 0.83, 95% CI 0.69-0.98), but not in women (HR 1.09, 95% CI 0.95-1.24) (p for sex interaction = .006). Each 1-ng/L higher fT4 was associated with increased mortality risk in men (HR 1.11, 95% CI 1.02-1.22), but not in women (HR 0.98, 95% CI 0.93-1.04) (p for sex interaction = .013). Each 1-pg/mL higher fT3 was associated with decreased mortality risk in women (HR 0.77, 95% CI 0.60-0.98), but not in men (HR 0.80, 95% CI 0.57-1.13). The inverse association between TSH and mortality was most pronounced in men older than 85 years. Conclusions: Among older outpatients with normal TSH, higher TSH and lower fT4 were associated with decreased mortality risk in men but not in women. When assessing thyroid status, sex and age should be taken into account. PMID- 27371956 TI - Optimization of hard clams, polychaetes, physical disturbance and denitrifying bacteria of removing nutrients in marine sediment. AB - Marine organisms are known to play important roles in transforming nutrients in sediments, however, guidelines to optimize sediment restoration are not available. We conducted a laboratory mesocosm experiment to investigate the role of hard clams, polychaetes, the degree of physical disturbance and denitrifying bacterial concentrations in removing total nitrogen (TN), total phosphorus (TP), and total organic carbon (TOC) in marine sediments. Response surface methodology was employed to analyze the results of initial experiments and in a subsequent experiment identified optimal combinations of parameters. Balancing the TN, TP, TOC removal efficiency, our model predicted 39% TN removal, 33% TP removal, and 42% TOC removal for a 14-day laboratory bioremediation trial using hard clams biomass of 1.2kgm(-2), physical disturbance depth of 16.4cm, bacterial density of 0.18Lm(-2), and polychaetes biomass of 0.16kgm(-2), respectively. These results emphasize the value of combining different species in field-based bioremediation. PMID- 27371955 TI - Species- and Strain-Specific Adaptation of the HSP70 Super Family in Pathogenic Trypanosomatids. AB - All eukaryotic genomes encode multiple members of the heat shock protein 70 (HSP70) family, which evolved distinctive structural and functional features in response to specific environmental constraints. Phylogenetic analysis of this protein family thus can inform on genetic and molecular mechanisms that drive species-specific environmental adaptation. Here we use the eukaryotic pathogen Leishmania spp. as a model system to investigate the evolution of the HSP70 protein family in an early-branching eukaryote that is prone to gene amplification and adapts to cytotoxic host environments by stress-induced and chaperone-dependent stage differentiation. Combining phylogenetic and comparative analyses of trypanosomatid genomes, draft genome of Paratrypanosoma and recently published genome sequences of 204 L. donovani field isolates, we gained unique insight into the evolutionary dynamics of the Leishmania HSP70 protein family. We provide evidence for (i) significant evolutionary expansion of this protein family in Leishmania through gene amplification and functional specialization of highly conserved canonical HSP70 members, (ii) evolution of trypanosomatid specific, non-canonical family members that likely gained ATPase-independent functions, and (iii) loss of one atypical HSP70 member in the Trypanosoma genus. Finally, we reveal considerable copy number variation of canonical cytoplasmic HSP70 in highly related L. donovani field isolates, thus identifying this locus as a potential hot spot of environment-genotype interaction. Our data draw a complex picture of the genetic history of HSP70 in trypanosomatids that is driven by the remarkable plasticity of the Leishmania genome to undergo massive intra chromosomal gene amplification to compensate for the absence of regulated transcriptional control in these parasites. PMID- 27371957 TI - Environmental quality in sediments of Cadiz and Algeciras Bays based on a weight of evidence approach (southern Spanish coast). AB - This research applies an integrated sediment quality assessment method using a weight of evidence approach to Cadiz and Algeciras Bays (southern Spain). The method is composed of several analyses (particle size profile, aqua regia extractable metals, acid labile metals, total organic carbon, toxicity bioassay with Photobacterium phosphoreum and macrobenthic community alteration). The proposed method provides a single result, the environmental degradation index (EDI). EDI defined samples as low degraded (outer areas of both bays) and moderately degraded (Inner Bay of Cadiz Bay, the surroundings of Algeciras port and the northern part of Algeciras Bay). These samples showed the highest concentration of aqua regia extractable metals, which exceeded effects range-low (ERL) for Zn (51-176mg/l), Cu (11-54mg/l), As (4.3-9.5mg/l), Hg (0.17-0.28mg/l), Ni (23-82mg/l), and. Cr (37-134mg/l). They also exceeded some quality criteria for total organic carbon (4.0-6.5%) and toxicity (120-240TU/g) and showed poor results for macrobenthic community. PMID- 27371958 TI - Antibiotic and metal resistance in a ST395 Pseudomonas aeruginosa environmental isolate: A genomics approach. AB - We analyzed the resistome of Pseudomonas aeruginosa E67, an epiphytic isolate from a metal-contaminated estuary. The aim was to identify genetic determinants of resistance to antibiotics and metals, assessing possible co-selection mechanisms. Identification was based on phylogenetic analysis and average nucleotide identity value calculation. MLST affiliated E67 to ST395, previously described as a high-risk clone. Genome analysis allowed identifying genes probably involved in resistance to antibiotics (e.g. beta-lactams, aminoglycosides and chloramphenicol) and metals (e.g. mercury and copper), consistent with resistance phenotypes. Several genes associated with efflux systems, as well as genetic determinants contributing to gene motility, were identified. Pseudomonas aeruginosa E67 possesses an arsenal of resistance determinants, probably contributing to adaptation to a polluted ecosystem. Association to mobile structures highlights the role of these platforms in multi drug resistance. Physical links between metal and antibiotic resistance genes were not identified, suggesting a predominance of cross-resistance associated with multidrug efflux pumps. PMID- 27371959 TI - The Neonatal Research Network: History since 2003, future directions and challenges. AB - The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neontal Research Network (NRN) was established in 1986 in response to the need for rigorous studies to guide care and management of sick and premature newborns. The network is comprise of clinical centers that perform clinical protocols to investigate the safety and efficay of treatment and management strategies for newborn infants as well as a data cordinating center. Infrastructure is set up for observational and interventional studies as well as neurodevelopmental follow-up of patients. The network has conducted trials and observational studies on major neonatal problems including pulmonary disease, neuroprotection, sepsis and infection, necrotizing enterocolitis, vaccine administration to preterm infants, retinopathy of prematurity, cardiovascular issues including blood pressure, human milk, growth and nutrition, hematologic issues, resuscitation, pulmonary hypertension, and neurodevelopmental outcome. This mechanism of clinical research for newborns has led to changes in care practices leading to improved outcomes for high-risk infants. PMID- 27371960 TI - Re: The effect of venous anatomy on the morphology of multiple sclerosis lesions: a susceptibility-weighted imaging study. A reply. PMID- 27371961 TI - Lesions of the jaws presenting as radiolucencies on cone-beam CT. AB - In order to compliment the current interest in lesions affecting the face and jaws in Clinical Radiology, this overview addresses recent developments in the classification, nomenclature, clinical and radiological diagnosis, and outcomes of treatment of the most important and frequent lesions that present as radiolucencies on conventional radiography of the jaws. Although termed "benign" a significant proportion of each odontogenic neoplasm can recur after conservative surgery. Two diagnostic flowcharts take the clinician from the radiological presentation of a lesion in the jaw to an appropriate diagnosis. The recent advent of cone-beam computed tomography (CBCT) can enhance the quality of the diagnosis and preoperative assessment of such lesions. CBCT images of typical benign neoplasms, cysts, and other phenomena affecting the face and jaws are included. The relative period prevalences of the lesions, based on the most recent UK reports, are included. The importance to the radiologist of an emerging lesion of the jaws, the glandular odontogenic cyst, is discussed. PMID- 27371962 TI - Re: The effect of venous anatomy on the morphology of multiple sclerosis lesions: a susceptibility-weighted imaging study. PMID- 27371963 TI - Association between the extent of sigmoid sinus dehiscence and an occurrence of pulsatile tinnitus: a retrospective imaging study. AB - AIM: To assess the extent of sigmoid sinus dehiscence (SSD) on high-resolution computed tomography venography (HRCTV) or high-resolution computed tomography (HRCT) images in pulsatile tinnitus (PT) and non-PT groups to determine whether there is an association between the extent of SSD and occurrence of PT. MATERIALS AND METHODS: Twenty-eight SSD patients with ipsilateral PT and 28 age- and gender matched SSD patients without PT who underwent HRCTV or HRCT were enrolled in this study and categorised into two groups: "PT group" and "non-PT group". The extent of SSD in each group was calculated and compared. RESULTS: The largest transverse diameter and largest vertical diameter of SSD in the PT group were 6.21+/-1.7 and 6.15+/-2.19 mm, respectively. The largest transverse diameter and largest vertical diameter of SSD in the non-PT group were 3.06+/-1.38 and 2.51+/-1.03 mm, respectively. The extent of SSD was statistically different between the two groups (p<0.001; p<0.001). CONCLUSIONS: As a cause of PT, SSD can also occur in individuals without PT symptoms. Preliminary findings suggest that there may be a potential correlation between the extent of SSD and an occurrence of PT. PMID- 27371964 TI - Yew (Taxus baccata) and foxglove (Digitalis spp.): toxic principles are very different. PMID- 27371965 TI - Eosinophil polyunsaturated fatty acid metabolism and its potential control of inflammation and allergy. AB - Polyunsaturated fatty acids (PUFAs) exhibit a range of biological effects, many of which are mediated through the formation and actions of their bioactive metabolites. It is well appreciated that dietary PUFA balance affects inflammation and/or allergic diseases, and recent advances in liquid chromatography tandem mass spectrometry (LC-MS/MS)-based mediator lipidomics have revealed a potential link between PUFA metabolism and biological phenotypes. This review presents insights into the emerging roles of eosinophil PUFA metabolism in controlling inflammatory responses and its potential involvement in allergy control. PMID- 27371966 TI - Does bathing frequency matter in pediatric atopic dermatitis? PMID- 27371967 TI - Treatment of moderate to severe pediatric asthma: Omalizumab and potential future use of monoclonal antibodies. PMID- 27371968 TI - The case for uniform controls in drug policy studies. PMID- 27371969 TI - Managing pregnancy-associated breast cancer: Is more really better? PMID- 27371970 TI - Radial scars diagnosed on breast core biopsy: Frequency of atypia and carcinoma on excision and implications for management. AB - AIMS: The risk of finding carcinoma in excisions following a core needle biopsy diagnosis of radial scar is not well defined and clinical management is variable. The aim of this study is to determine the frequency of high-risk lesions, ductal carcinoma in situ, and invasive carcinoma in excisions following a core biopsy diagnosis of radial scar. METHODS AND RESULTS: Dedicated breast pathologists and radiologists correlated the histologic and radiologic findings and categorized radial scars as the target lesion or an incidental finding. High-risk lesions were defined as atypical hyperplasia or classical lobular carcinoma in situ. Of the 79 radial scars identified over a 14-year period, 22 were associated with atypia or carcinoma in the core biopsy. Thirty-seven (37) of the 57 benign radial scars underwent excision with benign findings in 30 (81%), high-risk lesions in six (16%), and flat epithelial atypia in one (3%). There were no upgrades to carcinoma. One patient with a benign radial scar developed a 3-mm focus of intermediate-grade estrogen receptor-positive ductal carcinoma in situ in the same quadrant of the ipsilateral breast 72 months after excision. One patient with an incidental un-excised benign radial scar was diagnosed with ductal carcinoma in situ at a separate site of suspicious calcifications. CONCLUSIONS: In this series, none of the benign radial scars was upgraded to carcinoma. Radial scar was the targeted lesion in all cases with high-risk lesions on excision. Surgical excision may not be mandatory for patients with benign incidental radial scars on core biopsy. PMID- 27371971 TI - Follicular right shift: Xenografting queens' ovarian tissue into severe combined imunnodeficiency mice and its responses to exogenous gonadotropin. AB - Ovarian xenografting is an auxiliary reproductive technique that allows the conservation of germplasm of high-value livestock and endangered species. The use of exogenous gonadotropins assists in developing xenografted tissues and obtaining viable follicles for in vitro embryo production; however, this use has not been reported in the xenografting of cats' (Felis catus) ovaries with C57BL/6 female SCID mice (Mus musculus) as recipients. Therefore, the aim of this study was to evaluate the responses of queens' ovaries to eCG when grafted into C57BL/6 female SCID mice. Ovarian cortex fragments from queens were grafted under the kidney capsule of 15 C57BL/6 SCID mice after bilateral ovariectomy. After 45 days, the recipients were divided into two groups: those that did not receive hormone induction (eCG-), which were euthanized at the time of induction, and those that received hormonal induction (eCG+), which were euthanized 48 hours later. All the tissues collected were histologically processed. The proportions of the different ovarian follicles were compared by chi-square test. The morphology of the follicles was compared between the experimental groups by Tukey (primordial, primary, and secondary follicles) and Kruskal-Wallis (antral follicles) tests. Macroscopically, we observed a few antral follicles that were over 1 mm in size in grafts treated with eCG. Microscopically, follicles of all categories were observed in the grafts, and all had normal morphology for the species studied. However, larger primordial and primary follicles were observed in the eCG+ transplants than those in the eCG- transplants. There was a decrease in primordial follicles and an increase in the other follicles, particularly in the antral follicles of the eCG+ group, a phenomenon that we propose to term "follicular right shift". Luteinized follicles were also observed in grafts treated with eCG. Therefore, treatment with eCG is effective for follicular development but does not provoke a good superovulatory response, so the correct application time should be identified. Other protocols should be tested, to obtain viable follicles that can be used for in vitro embryo production. PMID- 27371972 TI - Accelerated follicle growth during the culture of isolated caprine preantral follicles is detrimental to follicular survival and oocyte meiotic resumption. AB - This study investigated the effect of androstenedione (A4) alone or in association with different concentrations of bovine recombinant FSH on the IVC of isolated goat preantral follicles. Follicles were mechanically isolated from ovarian tissue and cultured for 18 days in alpha-minimum essential medium supplemented or not with A4 (10 ng/mL) alone or in association with fixed (A4 + FixFSH: 100 ng/mL) or sequential (A4 + SeqFSH: Day 0, 100 ng/mL; Day 6, 500 ng/mL; Day 12, 1000 ng/mL) concentrations of FSH. After 18 days, the oocytes were recovered for IVM and fluorescence analysis. At Day 18 of culture, only A4 + SeqFSH treatment showed a lower (P < 0.05) rate of intact follicles, survival probability, and meiotic resumption, as well as higher (P < 0.05) percentage of degeneration and/or extrusion after antrum formation. Taken together, these results reported a positive correlation between fast-growing follicles and follicles that degenerated and/or extruded after antrum formation. When compared with control, the addition of A4 alone or in association of FSH did not increase (P > 0.05) the estradiol production or androstenedione levels on Day 6. However, on Day 18, the androstenedione levels were significantly lower in A4 + SeqFSH treatment when compared with A4 alone or to A4 + FixFSH treatments, whereas the estradiol production did not differ (P > 0.05). In summary, this study found that accelerated follicle growth negatively impacted the morphology of caprine preantral follicle cultured in vitro. In addition, the association of androstenedione with increasing concentration of FSH was detrimental to follicular survival and oocyte meiotic resumption. PMID- 27371973 TI - Pin-photodiode array for the measurement of fan-beam energy and air kerma distributions of X-ray CT scanners. AB - PURPOSE: Patient dose estimation in X-ray computed tomography (CT) is generally performed by Monte Carlo simulation of photon interactions within anthropomorphic or cylindrical phantoms. An accurate Monte Carlo simulation requires an understanding of the effects of the bow-tie filter equipped in a CT scanner, i.e. the change of X-ray energy and air kerma along the fan-beam arc of the CT scanner. To measure the effective energy and air kerma distributions, we devised a pin-photodiode array utilizing eight channels of X-ray sensors arranged at regular intervals along the fan-beam arc of the CT scanner. METHODS: Each X-ray sensor consisted of two plate type of pin silicon photodiodes in tandem - front and rear photodiodes - and of a lead collimator, which only allowed X-rays to impinge vertically to the silicon surface of the photodiodes. The effective energy of the X-rays was calculated from the ratio of the output voltages of the photodiodes and the dose was calculated from the output voltage of the front photodiode using the energy and dose calibration curves respectively. RESULTS: The pin-photodiode array allowed the calculation of X-ray effective energies and relative doses, at eight points simultaneously along the fan-beam arc of a CT scanner during a single rotation of the scanner. CONCLUSIONS: The fan-beam energy and air kerma distributions of CT scanners can be effectively measured using this pin-photodiode array. PMID- 27371974 TI - Modeling complement-driven diseases in transgenic mice: Values and limitations. AB - Remarkable advances have been made over past decades in understanding the pathogenesis of complement-mediated diseases. This has led to development of new therapies for, and in some cases re-classification of, complement-driven diseases. This success is due to not only insight from human patients but also studies using transgenic animal models. Animal models that mimic human diseases are useful tools to understand the mechanism of disease and develop new therapies but there are also limitations due to species differences in their complement systems. This review provides a summary of transgenic animal models for three human diseases that are at the forefront of anti-complement therapy, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G). They are discussed here as examples to highlight the values and limitations of animal modeling in complement-driven diseases. PMID- 27371975 TI - Complement-coagulation crosstalk on cellular and artificial surfaces. AB - The humoral serine proteases of the complement system and the coagulation system play central roles during the events of an inflammatory response. While the complement system confers immunoprotective and -regulatory functions, the coagulation cascade is responsible to ensure hemostatic maintenance. Although these two systems individually unfold during inflammation, several studies have reported on the "crosstalk" between components of the complement and the coagulation system in the fluid phase. However, both cascades are usually initiated on or in close proximity to foreign or activated surfaces, and there is increasing evidence for interacting complement and coagulation proteins on various superficial areas on endothelium, circulating entities like platelets, leukocytes, microparticles and pathogens, and even on artificial surfaces. This review aims at summarizing these interactions to complete the picture. PMID- 27371976 TI - A new perspective on the application of mosquito repellents. PMID- 27371978 TI - Medicalisation and its discontents. PMID- 27371977 TI - Efficacy of topical mosquito repellent (picaridin) plus long-lasting insecticidal nets versus long-lasting insecticidal nets alone for control of malaria: a cluster randomised controlled trial. AB - BACKGROUND: Although effective topical repellents provide personal protection against malaria, whether mass use of topical repellents in addition to long lasting insecticidal nets can contribute to a further decline of malaria is not known, particularly in areas where outdoor transmission occurs. We aimed to assess the epidemiological efficacy of a highly effective topical repellent in addition to long-lasting insecticidal nets in reducing malaria prevalence in this setting. METHODS: A cluster randomised controlled trial was done in the 117 most endemic villages in Ratanakiri province, Cambodia, to assess the efficacy of topical repellents in addition to long-lasting insecticidal nets in controlling malaria in a low-endemic setting. We did a pre-trial assessment of village accessibility and excluded four villages because of their inaccessibility during the rainy season. Another 25 villages were grouped because of their proximity to each other, resulting in 98 study clusters (comprising either a single village or multiple neighbouring villages). Clusters were randomly assigned (1:1) to either a control (long-lasting insecticidal nets) or intervention (long-lasting insecticidal nets plus topical repellent) study group after a restricted randomisation. All clusters received one long-lasting insecticidal net per individual, whereas those in the intervention group also received safe and effective topical repellents (picaridin KBR3023, SC Johnson, Racine, WI, USA), along with instruction and promotion of its daily use. Cross-sectional surveys of 65 randomly selected individuals per cluster were done at the beginning and end of the malaria transmission season in 2012 and 2013. The primary outcome was Plasmodium species-specific prevalence in participants obtained by real-time PCR, assessed in the intention-to-treat population. Complete safety analysis data will be published seperately; any ad-hoc adverse events are reported here. This trial is registered with ClinicalTrials.gov, number NCT01663831. FINDINGS: Of the 98 clusters that villages were split into, 49 were assigned to the control group and 49 were assigned to the intervention group. Despite having a successful distribution system, the daily use of repellents was suboptimum. No post intervention differences in PCR plasmodium prevalence were observed between study groups in 2012 (4.91% in the control group vs 4.86% in the intervention group; adjusted odds ratio [aOR] 1.01 [95% CI 0.60-1.70]; p=0.975) or in 2013 (2.96% in the control group vs 3.85% in the intervention group; aOR 1.31 [0.81-2.11]; p=0.266). Similar results were obtained according to Plasmodium species (1.33% of participants in the intervention group vs 1.10% in the intervention group were infected with Plasmodium falciparum; aOR 0.83 [0.44-1.56]; p=0.561; and 1.85% in the control group vs 2.67% in the intervention group were infected with Plasmodium vivax; aOR 1.51 [0.88-2.57]; p=0.133). 41 adverse event notifications from nine villages were received, of which 33 were classified as adverse reactions (11 of these 33 were cases of repellent abuse through oral ingestion, either accidental or not). All participants with adverse reactions fully recovered and 17 were advised to permanently stop using the repellent. INTERPRETATION: Mass distribution of highly effective topical repellents in resource-sufficient conditions did not contribute to a further decline in malaria endemicity in a pre-elimination setting in the Greater Mekong subregion. Daily compliance and appropriate use of the repellents remains the main obstacle. FUNDING: Bill & Melinda Gates Foundation. PMID- 27371979 TI - Does the United Nations care about mental health? PMID- 27371981 TI - Corrections. PMID- 27371980 TI - Schizophrenia: inorganic no more. PMID- 27371982 TI - Corrections. PMID- 27371983 TI - Scaling-up of treatment of depression and anxiety - Authors' reply. PMID- 27371984 TI - Scaling-up of treatment of depression and anxiety. PMID- 27371985 TI - Psychiatric beds and increased suicide rates in England - Authors' reply. PMID- 27371986 TI - Psychiatric beds and increased suicide rates in England. PMID- 27371988 TI - Luciana Berger: UK Shadow Minister for Mental Health. PMID- 27371989 TI - Concordance of ICD-11 and DSM-5 definitions of alcohol and cannabis use disorders: a population survey. AB - The proposed criteria for alcohol and cannabis use disorders in the 11th edition of ICD (ICD-11) will be presented to the World Health Assembly in 2017, but the beta-phase descriptions have been released. We compared them with those in the tenth edition (ICD-10) and the American Psychiatric Association's DSM fourth edition (DSM-IV) and fifth edition (DSM-5), in a nationally representative sample of adult Australians. Disorders were assessed with the WHO World Mental Health Composite International Diagnostic Interview. The proportions classified as being dependent on alcohol and cannabis were similar with ICD-10, ICD-11, and DSM-IV, whereas for DSM-5, the proportion of lifetime users meeting the criteria for moderate to severe use (most comparable to dependence in the other systems) was far higher. We assessed whether criteria for alcohol and cannabis use described unidimensional syndromes for each, and all definitions seemed to do so. Classification of alcohol and cannabis use disorders, although simplified in ICD 11, was in almost perfect agreement with the classifications of ICD-10 and DSM IV. With DSM-5, use disorder seemed to capture a different aspect of problematic use and selected a different group of individuals from the other systems. How the newest definitions will become used remains to be seen. The choice of classification might depend on the clinical population of interest. PMID- 27371990 TI - Persecutory delusions: a cognitive perspective on understanding and treatment. AB - A spectrum of severity of paranoia (unfounded thoughts that others are deliberately intending to cause harm) exists within the general population. This is unsurprising: deciding whether to trust or mistrust is a vital aspect of human cognition, but accurate judgment of others' intentions is challenging. The severest form of paranoia is persecutory delusions, when the ideas are held with strong conviction. This paper presents a distillation of a cognitive approach that is being translated into treatment for this major psychiatric problem. Persecutory delusions are viewed as threat beliefs, developed in the context of genetic and environmental risk, and maintained by several psychological processes including excessive worry, low self-confidence, intolerance of anxious affect and other internal anomalous experiences, reasoning biases, and the use of safety seeking strategies. The clinical implication is that safety has to be relearned, by entering feared situations after reduction of the influence of the maintenance factors. An exciting area of development will be a clinical intervention science of how best to enhance learning of safety to counteract paranoia. PMID- 27371991 TI - Tumor dose-volume response in image-guided adaptive brachytherapy for cervical cancer: A meta-regression analysis. AB - PURPOSE: Image-guided adaptive brachytherapy is a high precision technique that allows dose escalation and adaptation to tumor response. Two monocentric studies reported continuous dose-volume response relationships, however, burdened by large confidence intervals. The aim was to refine these estimations by performing a meta-regression analysis based on published series. METHODS AND MATERIALS: Eligibility was limited to series reporting dosimetric parameters according to the Groupe Europeen de Curietherapie-European SocieTy for Radiation Oncology recommendations. The local control rates reported at 2-3 years were confronted to the mean D90 clinical target volume (CTV) in 2-Gy equivalent using the probit model. The impact of each series on the relationships was pondered according to the number of patients reported. RESULTS: An exhaustive literature search retrieved 13 series reporting on 1299 patients. D90 high-risk CTV ranged from 70.9 to 93.1 Gy. The probit model showed a significant correlation between the D90 and the probability of achieving local control (p < 0.0001). The D90 associated to a 90% probability of achieving local control was 81.4 Gy (78.3-83.8 Gy). The planning aim of 90 Gy corresponded to a 95.0% probability (92.8-96.3%). For the intermediate-risk CTV, less data were available, with 873 patients from eight institutions. Reported mean D90 intermediate-risk CTV ranged from 61.7 to 69.1 Gy. A significant dose-volume effect was observed (p = 0.009). The D90 of 60 Gy was associated to a 79.4% (60.2-86.0%) local control probability. CONCLUSION: Based on published data from a high number of patients, significant dose-volume effect relationships were confirmed and refined between the D90 of both CTV and the probability of achieving local control. Further studies based on individual data are required to develop nomograms including nondosimetric prognostic criteria. PMID- 27371992 TI - A female case of aromatic l-amino acid decarboxylase deficiency responsive to MAO B inhibition. AB - BACKGROUND: Aromatic l-amino acid decarboxylase (AADC) deficiency is an autosomal recessive disorder, caused by defects in the DDC gene. AADC catalyzes the synthesis of the neurotransmitters dopamine and serotonin from l-dopa and 5-HT respectively. Most patients are bed ridden for life, with little response to treatment. We now report one female patient who improved her motor and cognitive function after being prescribed a MAO-B inhibitor. CASE: A five years old female presented with the typical clinical features of AADC deficiency. She was floppy, with no head control, had intermittent limb dystonia, and an upward deviation of the eyes (oculogyric crisis). This patient possessed compound heterozygous mutations in DDC (p.Trp105Cys, p.Pro129Ser), with a CSF draw indicating abnormal patterns of biogenic amine metabolites, compatible with AADC deficiency. RESULTS: After her diagnosis at 3years of age, medication with levodopa and vitamin B6 failed to show any efficacy. Subsequent administration with a MAO-B inhibitor improved her psychomotor functions to the extent that at 5years of age she could walk several meters with support. CONCLUSION: Our analyses of chemical findings, together with in silico structure predictions, lead us to hypothesize that this patient retained some AADC activity. In these cases, accurate diagnosis and early treatment should improve patient outcome. PMID- 27371993 TI - Protein-energy wasting and nutritional supplementation in patients with end-stage renal disease on hemodialysis. AB - BACKGROUND & AIMS: Protein-Energy Wasting (PEW) is the depletion of protein/energy stores observed in the most advanced stages of Chronic Kidney Disease (CKD). PEW is highly prevalent among patients on chronic dialysis, and is associated with adverse clinical outcomes, high morbidity/mortality rates and increased healthcare costs. This narrative review was aimed at exploring the pathophysiology of PEW in end-stage renal disease (ESRD) on hemodialysis. The main aspects of nutritional status evaluation, intervention and monitoring in this clinical setting were described, as well as the current approaches for the prevention and treatment of ESRD-related PEW. METHODS: An exhaustive literature search was performed, in order to identify the relevant studies describing the epidemiology, pathogenesis, nutritional intervention and outcome of PEW in ESRD on hemodialysis. RESULTS AND CONCLUSION: The pathogenesis of PEW is multifactorial. Loss of appetite, reduced intake of nutrients and altered lean body mass anabolism/catabolism play a key role. Nutritional approach to PEW should be based on a careful and periodic assessment of nutritional status and on timely dietary counseling. When protein and energy intakes are reduced, nutritional supplementation by means of specific oral formulations administered during the hemodialysis session may be the first-step intervention, and represents a valid nutritional approach to PEW prevention and treatment since it is easy, effective and safe. Omega-3 fatty acids and fibers, now included in commercially available preparations for renal patients, could lend relevant added value to macronutrient supplementation. When oral supplementation fails, intradialytic parenteral nutrition can be implemented in selected patients. PMID- 27371994 TI - Associations between sheep farmer attitudes, beliefs, emotions and personality, and their barriers to uptake of best practice: The example of footrot. AB - There is interest in understanding how farmers' behaviour influences their management of livestock. We extend the theory of planned behaviour with farmers attitudes, beliefs, emotions and personality to investigate how these are associated with management of livestock disease using the example of footrot (FR) in sheep. In May 2013 a one-year retrospective questionnaire was sent to 4000 sheep farmers in England, requesting data on lameness prevalence, management of footrot, farm/flock descriptors, and farmer-orientated themes: barriers to treating footrot, opinions and knowledge of footrot, relating to other people and personality. Principal component analysis (PCA) was used to make composite variables from explanatory variables and latent class (LC) analysis was used to subgroup farmers, based on nine managements of FR. Associations between LC and composite variables were investigated using multinomial logistic regression. Negative binomial regression was used to investigate associations between the proportion of lame sheep and composite and personality variables. The useable response rate was 32% and 97% of farmers reported having lame sheep; the geometric mean prevalence of lameness (GMPL) was 3.7% (95% CI 3.51%-3.86%). Participants grouped into three latent classes; LC1 (best practice-treat FR within 3days of sheep becoming lame; use injectable and topical antibiotics; avoid foot trimming), 11% farmers), LC2 (slow to act, 57%) and LC3 (slow to act, delayed culling, 32%), with GMPL 2.95%, 3.60% and 4.10% respectively. Farmers who reported the production cycle as a barrier to treating sheep with FR were more likely to be in LC2 (RRR 1.36) than LC1. Negative emotions towards FR were associated with higher risk of being in LC2 (RRR 1.39) than LC1. Knowledge of preventing FR spread was associated with a lower risk of being in LC2 (RRR 0.46) or LC3 (RRR 0.34) than LC1. Knowledge about FR transmission was associated with a lower risk of being in LC3 (RRR 0.64) than LC1. An increased risk of lameness was associated with the production cycle being a barrier to treating sheep with FR (IRR 1.13), negative emotions towards FR (IRR 1.13) and feelings of hopelessness towards FR (IRR 1.20). Conscientiousness (IRR 0.95) and understanding the importance of active control of lameness (IRR 0.76) were associated with reduced risk of lameness. We conclude that emotions and personality are associated with differences in farmer management of FR and prevalence of lameness. Further understanding how personality and emotions influence change in behaviour is key to increasing uptake of new information. PMID- 27371997 TI - The effect of a platelet-rich fibrin conduit on neurosensory recovery following inferior alveolar nerve lateralization: a preliminary clinical study. AB - This retrospective study aimed to assess the recovery of neurosensory dysfunction following modified inferior alveolar nerve (IAN) lateralization surgery compared to the conventional approach. Data from two groups of patients who underwent IAN lateralization in 2014 were included in this study. In one group, platelet-rich fibrin was placed over the IAN and this was protected with a collagen membrane conduit; the other group underwent the conventional IAN lateralization procedure. Implants were placed immediately. Neurosensory dysfunction was evaluated at 3, 6, and 12 months post-surgery. Demographic, neurosensory disturbance (NSD), subjective two-point discrimination test (TPD), and static light touch test (SLT) data were obtained. Twenty-three IAN lateralization procedures with the placement of 51 implants were performed in 14 patients. At the 6-month follow-up, the number of patients experiencing normal sensation was greater in the modified surgery group, but the 12-month follow-up results were the same in the two groups. More precise sensation was observed with the TPD in the modified group at 6 months, and the modified group demonstrated better SLT scores at 6 months. Although the two groups had comparable results at the 12-month follow-up, it was observed that the modified technique accelerated neural healing within 6 months and reduced the length of the discomfort period. PMID- 27371996 TI - Calcinosis is associated with digital ulcers and osteoporosis in patients with systemic sclerosis: A Scleroderma Clinical Trials Consortium study. AB - OBJECTIVES: We sought to identify the clinical factors associated with calcinosis in an international multicenter collaborative effort with the Scleroderma Clinical Trials Consortium (SCTC). METHODS: This is a retrospective cohort study of 5218 patients with systemic sclerosis (SSc). Logistic regression was used to obtain odds ratios (OR) relating calcinosis to various clinical features in multivariate analyses. RESULTS: A total of 1290 patients (24.7%) had calcinosis. In univariate analyses, patients with calcinosis were older than patients without calcinosis, more likely to be female, and had longer disease duration from the first non-Raynaud phenomenon symptom. Patients with calcinosis were more likely to have digital ulcers, telangiectasias, acro-osteolysis, cardiac disease, pulmonary hypertension, gastrointestinal involvement, arthritis, and osteoporosis, but less likely to have muscle disease. Anti-Scl-70, RNA-polymerase III, and U1-RNP autoantibodies were significantly less common in patients with calcinosis, while anticentromere (ACA), anti-PM/Scl, and anticardiolipin antibodies were more frequent. In multivariate analysis, the strongest associations with calcinosis were digital ulcers (OR = 3.9; 95% CI: 2.7-5.5; p < 0.0001) and osteoporosis (OR = 4.2; 95% CI: 2.3-7.9; p < 0.0001). CONCLUSION: One quarter of patients with SSc have calcinosis at some time during their illness. Our data confirm a strong association of calcinosis with digital ulcers, and support a novel association with osteoporosis. PMID- 27371998 TI - The impact of treatment on quality of life of patients with head and neck cancer and its association with prognosis. AB - BACKGROUND: Information is scarce regarding the impact of treatment on Health Related Quality of Life (HRQL) of patients with Head and Neck (H&N) cancers. We assessed the effect of treatment on HRQL and its association with prognosis in H&N cancer. PATIENTS AND METHODS: Patients with H&N cancer in whom HRQL was assessed before and after treatment. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-H&N35 instruments were used. Association of changes in patients' HRQL after treatment with Loco-Regional Recurrence (LRR) and Overall Survival (OS) was investigated. RESULTS: One hundred sixty patients were included; scales of the baseline assessment of HRQL were moderately associated with LRR and OS, but the impact of treatment on most HRQL scales was strongly associated with OS. By multivariate analysis, baseline assessment of Global Health, Physical, HN Teeth, HN Dry mouth, and HN Cough scales, and impact of treatment on the Physical and Pain scales comprised independent variables associated with LRR. Male gender, positive lymph nodes, baseline assessment of Role, HN Pain, HN Cough, and impact of treatment on Emotion, Pain, Financial, HN Swallowing, HN Social contact, and the interaction of HN Pain-change in Pain scales were associated with OS. Both multivariate models were adjusted by the neoplasm's site of origin. CONCLUSION: Aside from well-known clinical-pathologic prognostic factors in H&N cancers, HRQL assessment, both prior to and after treatment, provides significant prognostic information and should be measured. Design of therapeutic clinical trials in patients with H&N cancers should consider these novel prognostic factors. PMID- 27371999 TI - Percutaneous thermal ablation: A new treatment line in the multidisciplinary management of metastatic leiomyosarcoma? AB - BACKGROUND: The role of percutaneous thermal ablation (PTA) in the multidisciplinary management of metastatic leiomyosarcoma (LMS) has not been thoroughly evaluated. MATERIALS AND METHODS: Single institution retrospective review of all patients with LMS metastases treated with PTA from June 2004 to December 2014. Iterative PTAs were performed as a multifocal treatment for all recurrent or residual macroscopic metastases discovered on imaging after completion of systemic treatment, or alternatively as a targeted treatment of selective metastases found to be progressive on systemic treatment. The primary endpoint was the time to untreatable progression (TTUP), recorded as the time elapsed between the first PTA and the re-initiation of systemic chemotherapy to treat disease progression. Secondary endpoints were overall survival, the 1, 3 and 5-year survival rates, and local control rate. RESULTS: A total of 93 LMS metastases (average diameter 18.2 mm, range 3-45 mm) were successfully treated in 30 patients over 50 treatment sessions with a median follow-up of 34.6 months. The median TTUP was 14.2 months (range 2.4-122.8). The median overall survival after PTA was 48.3 months and the 1, 3 and 5-year overall survival rates were 96.7% (95%CI 84.3-100.0%), 62.0% (95%CI 45.8-84.0%), and 28.3% (95%CI 13.5-59.1%) respectively. Local control rate at 1 year was 95.2% and at 3 years was 89.4%. CONCLUSION: Iterative PTA is an effective treatment line option for appropriately selected patients with metastatic LMS that can delay re-initiation of systemic chemotherapy. PMID- 27372000 TI - Immediate pedicled gracilis flap in radial forearm flap phalloplasty for transgender male patients to reduce urinary fistula. AB - BACKGROUND AND AIM: Radial forearm phalloplasty is accompanied by high rates of fistula formation. We examined the effect of placing a pedicled gracilis myofascial flap around the urethral anastomosis at the time of radial forearm flap transfer on the development of postoperative urethrocutaneous fistula. METHODS: Fifteen patients underwent phalloplasty with urethroplasty between June 2012 and October 2015, and they met the inclusion and exclusion criteria for the study. We retrospectively reviewed patients' medical records and extracted patient demographic data, prelamination technique used (mucosa, skin graft, both, or neither), and whether or not a gracilis myofascial flap was harvested at the time of flap transfer and used to reinforce the native-neourethral anastomosis. The chi-squared test was used to evaluate the association between the presence of a gracilis flap and fistula formation. RESULTS: Four patients received a gracilis flap as part of their primary phalloplasty operation. None of these patients developed a fistula. Eleven patients did not receive a gracilis flap at the time of initial surgery and seven developed a fistula. DISCUSSION: In our patient series, inclusion of a pedicled myofascial gracilis flap at the time of radial forearm phalloplasty with urethroplasty was associated with an absence of fistula formation. Therefore, we have since made inclusion of this flap a standard practice for all transmales undergoing phalloplasty with urethroplasty. PMID- 27372001 TI - When Maxwellian demon meets action at a distance: Comment on "Disentangling DNA molecules" by Alexander Vologodskii. PMID- 27372003 TI - The lower trapezius island myocutaneous flap in tunnelled technique to cover complicated tissue defects located between the craniocervical and cervicothoracic junction following spinal surgery. AB - PURPOSE: Stable coverage of complicated defects located between the craniocervical and cervicothoracic junction following wound healing disturbance after spinal surgery can be challenging. Especially in cases where devices are exposed, well-vascularized coverage is required to achieve stable wound conditions. Therefore, the aim of the present study was to evaluate the clinical outcome of the lower trapezius island myocutaneous flap (LTIMF) as a possible treatment option. MATERIALS AND METHODS: Four patients with a mean age of 68.8 years (ranging from 50 to 93 years) with wound healing disturbance following spinal surgery leading to defects of the dorsal neck/upper back refractory to conservative treatment and surgical debridement were included. All defects were reconstructed with a LTIMF based on the transverse cervical artery. RESULTS: Mean follow-up was 16.5 months (ranging from 5 to 30 months). No major flap failure occurred; minor complications in three patients including lateral superficial skin necrosis were easily handled. In all patients, excellent functional and aesthetic results were achieved. CONCLUSION: The lower trapezius island myocutaneous flap represents a reliable treatment option to cover complicated defects located between the craniocervical and cervicothoracic junction following wound disturbance after spinal surgery. PMID- 27372002 TI - Muscle Strength and Poststroke Hemiplegia: A Systematic Review of Muscle Strength Assessment and Muscle Strength Impairment. AB - OBJECTIVES: To systematically review (1) psychometric properties of criterion isokinetic dynamometry testing of muscle strength in persons with poststroke hemiplegia (PPSH); and (2) literature that compares muscle strength in patients poststroke with that in healthy controls assessed by criterion isokinetic dynamometry. DATA SOURCES: A systematic literature search of 7 databases was performed. STUDY SELECTION: Included studies (1) enrolled participants with definite poststroke hemiplegia according to defined criteria; (2) assessed muscle strength or power by criterion isokinetic dynamometry; (3) had undergone peer review; and (4) were available in English or Danish. DATA EXTRACTION: The psychometric properties of isokinetic dynamometry were reviewed with respect to reliability, validity, and responsiveness. Furthermore, comparisons of strength between paretic, nonparetic, and comparable healthy muscles were reviewed. DATA SYNTHESIS: Twenty studies covering 316 PPSH were included. High intraclass correlation coefficient (ICC) inter- and intrasession reliability was reported for isokinetic dynamometry, which was independent of the tested muscle group, contraction mode, and contraction velocity. Slightly higher ICC values were found for the nonparetic extremity. Standard error of the mean (SEM) values showed that a change of 7% to 20% was required for a real group change to take place for most muscle groups, with the knee extensors showing the smallest SEM% values. The muscle strength of paretic muscles showed deficits when compared with both healthy and nonparetic muscles, independent of muscle group, contraction mode, and contraction velocity. Nonparetic muscles only showed minor strength impairments when compared with healthy muscles. CONCLUSIONS: Criterion isokinetic dynamometry is a reliable test in persons with stroke, generally showing marked reductions in muscle strength of paretic and, to a lesser degree, nonparetic muscles when compared with healthy controls, independent of muscle group, contraction mode, and contraction velocity. PMID- 27372004 TI - Enhanced mannan-derived fermentable sugars of palm kernel cake by mannanase catalyzed hydrolysis for production of biobutanol. AB - Catalytic depolymerization of mannan composition of palm kernel cake (PKC) by mannanase was optimized to enhance the release of mannan-derived monomeric sugars for further application in acetone-butanol-ethanol (ABE) fermentation. Efficiency of enzymatic hydrolysis of PKC was studied by evaluating effects of PKC concentration, mannanase loading, hydrolysis pH value, reaction temperature and hydrolysis time on production of fermentable sugars using one-way analysis of variance (ANOVA). The ANOVA results revealed that all factors studied had highly significant effects on total sugar liberated (P<0.01). The optimum conditions for PKC hydrolysis were 20% (w/v) PKC concentration, 5% (w/w) mannanase loading, hydrolysis pH 4.5, 45 degrees C temperature and 72h hydrolysis time. Enzymatic experiments in optimum conditions revealed total fermentable sugars of 71.54+/ 2.54g/L were produced including 67.47+/-2.51g/L mannose and 2.94+/-0.03g/L glucose. ABE fermentation of sugar hydrolysate by Clostridium saccharoperbutylacetonicum N1-4 resulted in 3.27+/-1.003g/L biobutanol. PMID- 27372005 TI - Saccharification of microalgae biomass obtained from wastewater treatment by enzymatic hydrolysis. Effect of alkaline-peroxide pretreatment. AB - An enzymatic method for the carbohydrate hydrolysis of different microalgae biomass cultivated in domestic (DWB) and pig manure (PMWB) wastewaters, at different storage conditions (fresh, freeze-dried and reconstituted), was evaluated. The DWB provided sugars yields between 40 and 63%, although low xylose yields (< 23.5%). Approximately 2% of this biomass was converted to byproducts as succinic, acetic and formic acids. For PMWB, a high fraction of the sugars (up to 87%) was extracted, but mainly converted into acetic, butyric and formic acids, which was attributed to the bacterial action. In addition, the performance of an alkaline-peroxide pretreatment, conducted for 1h, 50 degrees C and H2O2 concentrations from 1 to 7.5% (w/w), was essayed. The hydrolysis of pretreated microalgae supported a wide range of sugars extraction for DWB (55-90%), and 100% for PMWB. Nevertheless, a large fraction of these sugars (~30% for DWB and 100% for PMWB) was transformed to byproducts. PMID- 27372006 TI - A novel paradigm for the high-efficient production of phycocyanin from Galdieria sulphuraria. AB - A novel cultivation strategy called "Sequential Heterotrophy-Dilution Photoinduction" was successfully applied in the cultivation of Galdieria sulphuraria for efficient production of phycocyanin (PC). Algae cells were firstly cultivated heterotrophically to achieve high cell density. The maximal dry cell weight of 17.8gL(-1) and maximal biomass productivity of 103.1mgL(-1)h( 1) were obtained. Then, a dilution step was applied to obtain a suitable cell concentration and finally these cells were transferred to high light condition for phycocyanin accumulation. During the photoinduction step, cells could accumulate phycocyanin up to 13.88% of dry cell weight in a cultivation period of 8days. By this technology, total PC productivity far surpassed those reported in all literatures of Galdieria sulphuraria, and was 147-fold and 12-fold of those in photoautotrophic and heterotrophic technologies, respectively. Therefore, this strategy provides a promising approach for high-efficient phycocyanin production from Galdieria sulphuraria to meet its mass cultivation and commercialization application. PMID- 27372007 TI - Improvement of the catalytic performance of a Bispora antennata cellulase by replacing the N-terminal semi-barrel structure. AB - The aim of this work was to study the contribution of the N-terminal structure to cellulase catalytic performance. A wild-type cellulase (BaCel5) of glycosyl hydrolase (GH) family 5 from Bispora antennata and two hybrid enzymes (BaCel5(127) and BaCel5(167)) with replacement of the N-terminal (betaalpha)3 (127 residues) or (betaalpha)4 (167 residues)-barrel with the corresponding sequences of TeEgl5A from Talaromyces emersonii were produced in Pichia pastoris and biochemically characterized. BaCel5 exhibited optimal activity at pH 5.0 and 50 degrees C but had low catalytic efficiency (25.4+/-0.8mLs(-1)mg(-1)). In contrast, BaCel5(127) and BaCel5(167) showed similar enzymatic properties but improved catalytic performance. When using CMC-Na, barley beta-glucan, lichenan, and cellooligosaccharides as substrates, BaCel5(127) and BaCel5(167) had increased specific activities and catalytic efficiencies by ~1.8-6.7-fold and ~1.0-4.7-fold, respectively. The catalytic efficiency of BaCel5(167) was even higher than that of parental proteins. The underlying mechanism was analyzed by molecular docking and molecular dynamic simulation. PMID- 27372008 TI - Performance of a microbial fuel cell-based biosensor for online monitoring in an integrated system combining microbial fuel cell and upflow anaerobic sludge bed reactor. AB - A hybrid system integrating a microbial fuel cell (MFC)-based biosensor with upflow anaerobic sludge blanket (UASB) was investigated for real-time online monitoring of the internal operation of the UASB reactor. The features concerned were its rapidity and steadiness with a constant operation condition. In addition, the signal feedback mechanism was examined by the relationship between voltage and time point of changed COD concentration. The sensitivity of different concentrations was explored by comparing the signal feedback time point between the voltage and pH. Results showed that the electrical signal feedback was more sensitive than pH and the thresholds of sensitivity were S=3*10(-5)V/(mg/L) and S=8*10(-5)V/(mg/L) in different concentration ranges, respectively. Although only 0.94% of the influent COD was translated into electricity and applied for biosensing, this integrated system indicated great potential without additional COD consumption for real-time monitoring. PMID- 27372009 TI - Enhanced adsorption of cesium on PVA-alginate encapsulated Prussian blue-graphene oxide hydrogel beads in a fixed-bed column system. AB - A continuous fixed-bed column study was performed using PVA-alginate encapsulated Prussian blue-graphene oxide (PB-GO) hydrogel beads as a novel adsorbent for the removal of cesium from aqueous solutions. The effects of different operating parameters, such as initial cesium concentration, pH, bed height, flow rate, and bead size, were investigated. The maximum adsorption capacity of the PB-GO hydrogel beads was 164.5mg/g at an initial cesium concentration of 5mM, bed height of 20cm, and flow rate of 0.83mL/min at pH 7. The Thomas, Adams-Bohart, and Yoon-Nelson models were applied to the experimental data to predict the breakthrough curves using non-linear regression. Although both the Thomas and Yoon-Nelson models showed good agreement with the experimental data, the Yoon Nelson model was found to provide the best representation for cesium adsorption on the adsorbent, based on the chi(2) analysis. PMID- 27372010 TI - Rheological characterization of digested sludge by solid sphere impact. AB - An impact method was applied to investigate the rheological characteristics of digested sludge and reveal its transient dynamics. A high-speed camera allowed visualizing the dynamic impact process and observing interaction between impacting sphere and targeted sludge. A damping oscillation was observed after the impact. The crater diameter followed an exponential function, while the crater depth varied as a logarithmic function of both sphere diameter and free fall height. Furthermore, the viscosity and elasticity of digested sludge were evaluated by establishing a simplified impact drag force model. The impact elastic modulus was consistent with the Young's modulus measured by a penetrometer. The impact viscosity was reasonable as the estimated impact shear stress was greater than the yield stress of digested sludge resulting in the formation of crater. The impact method offers an alternative way to reveal the viscoelasticity of digested sludge through a dynamic process. PMID- 27372011 TI - The feasibility of an up-flow partially aerated biological filter (U-PABF) for nitrogen and COD removal from domestic wastewater. AB - An up-flow partially aerated biological filter (U-PABF) was developed to study the removal of nitrogen and chemical oxygen demand (COD) from synthetic domestic wastewater. The removal of NH4(+)-N was primarily attributed to adsorption in the zeolite U-PABF and to bioprocesses in the ceramic U-PABF. When the hydraulic retention time (HRT) was 5.2h, the ceramic U-PABF achieved a good performance and the NH4(+)-N, total nitrogen (TN), and COD removal efficiency reached 99.08+/ 8.79%, 72.83+/-0.68%, and 89.38+/-1.04%, respectively. The analysis of NH4(+)-N, NO3(-)-N, NO2(-)-N, and TN at different depths revealed the simultaneous existence of nitrification-denitrification, and anaerobic ammonium oxidation (anammox) in ceramic U-PABF. Illumina pyrosequencing confirmed the existence of Planctomycetes, which are responsible for anammox. The results indicated that the nitrification-denitrification and anammox all contributed to the high removal of NH4(+)-N, TN, and COD in the U-PABF. PMID- 27372012 TI - Production of a bioflocculant from Pseudomonas veronii L918 using the hydrolyzate of peanut hull and its application in the treatment of ash-flushing wastewater generated from coal fired power plant. AB - In this study, bioflocculant produced by Pseudomonas veronii L918 was applied to treat ash-flushing wastewater. The strain L918 could convert the hydrolyzate of peanut hull into bioflocculant, which can effectively reduce the production cost of bioflocculant. The yield of 3.39g/L bioflocculant MBF-L918 was achieved when 300mL/L peanut hull hydrolyzate was used as carbon source. The bioflocculant MBF L918 contains 77.14% polysaccharides and 4.84% proteins, and the molecular weight (MW) of MBF-L918 is 24.77kDa. Furthermore, MBF-L918 showed good flocculating efficiency of 92.51% to ash-flushing wastewater when 2.83mg/L MBF-L918 was added, and thus achieved the recycling of ash-flushing wastewater. This study reported for the first time that the bioflocculant was produced using peanut hull hydrolyzate and effectively applied in the treatment of coal ash-flushing wastewater. PMID- 27372013 TI - Fabrication of core-shell structured magnetic nanocellulose base polymeric ionic liquid for effective biosorption of Congo red dye. AB - Ionic liquids are considered to be a class of environmentally friendly compounds as combination of them with bioresource polymeric substances such as; cellulose, constitute emerging coating materials. Biosorption by polymeric ionic liquids exhibits an attractive green way that involves low cost and irrespective of toxicity. As a result, a novel polymeric ionic liquid has been developed by the reaction of one step synthesized Fe3O4-cellulose nanohybrid, epichlorohydrin and 1-methylimidazole and employed as a green sorbent for efficient biosorption of Congo red dye. Effective parameters on dye removing as well as their interactions were determined with response surface methodology (RSM). Congo red adsorption showed fast equilibrium time (11min) with maximum uptake of 131mgg(-1). Isotherm study revealed that Langmuir adsorption model can better describe dye adsorption behavior. Regeneration of the sorbent was performed with a mixture of methanol acetone-NaOH (3.0molL(-1)) solution. PMID- 27372014 TI - Regulation of Retinoic Acid Inducible Gene-I (RIG-I) Activation by the Histone Deacetylase 6. AB - Retinoic acid inducible gene-I (RIG-I) is a cytosolic pathogen recognition receptor that initiates the immune response against many RNA viruses. Upon RNA ligand binding, RIG-I undergoes a conformational change facilitating its homo oligomerization and activation that results in its translocation from the cytosol to intracellular membranes to bind its signaling adaptor protein, mitochondrial antiviral-signaling protein (MAVS). Here we show that RIG-I activation is regulated by reversible acetylation. Acetyl-mimetic mutants of RIG-I do not form virus-induced homo-oligomers, revealing that acetyl-lysine residues of the RIG-I repressor domain prevent assembly to active homo-oligomers. During acute infection, deacetylation of RIG-I promotes its oligomerization upon ligand binding. We identify histone deacetylase 6 (HDAC6) as the deacetylase that promotes RIG-I activation and innate antiviral immunity to recognize and restrict RNA virus infection. PMID- 27372015 TI - Assessing Hemodynamically Significant CAD by Difference in Contrast Opacification of CT Angiograms: An Exercise in Seeing and Believing. PMID- 27372016 TI - Impact of TCFA on Unanticipated Ischemic Events in Medically Treated Diabetes Mellitus: Insights From the PROSPECT Study. AB - OBJECTIVES: This study sought to investigate the relationship between thin-cap fibroatheromas (TCFAs) on major adverse cardiac events (MACEs) arising from medically treated nonculprit lesions (NCLs) in patients with acute coronary syndromes (ACS) with and without diabetes mellitus (DM). BACKGROUND: MACEs occur frequently in patients with DM and ACS. The impact of plaque composition on subsequent MACEs in DM patients with ACS is unknown. METHODS: In the PROSPECT (Providing Regional Observations Study Predictors of Events in the Coronary Tree) study, using 3-vessel radiofrequency intravascular ultrasound, we analyzed the incidence of NCL-MACE in 2 propensity-matched groups according to the presence of DM and TCFA. RESULTS: Among 697 patients, 119 (17.7%) had DM. The 3-year total MACE rate (29.4% vs. 18.8%; p = 0.01) was significantly higher in patients with versus without DM, driven by a higher rate of NCL-MACE in DM (18.7% vs. 10.4%; p = 0.02). Propensity score matching generated 2 balanced groups with and without DM of 82 patients each. Among DM patients, the presence of >=1 TCFA was associated with higher NCL-MACE at 3 years (27.8% vs. 8.9% in patients without a TCFA, hazard ratio: 3.56; 95% confidence interval: 0.98 to 12.96; p = 0.04). DM patients without a TCFA had a similar 3-year rate of NCL-MACE as patients without DM (8.9% vs. 8.9%; hazard ratio: 1.09; 95% confidence interval: 0.27 to 4.41; p = 0.90). CONCLUSIONS: ACS patients with DM and >=1 TCFA have a high rate of NCL MACE at 3 years. In contrast, the prognosis of ACS patients with DM but no TCFAs is favorable and similar to patients without DM. PMID- 27372017 TI - Influence of Coronary Artery Diameter on Intracoronary Transluminal Attenuation Gradient During CT Angiography. AB - OBJECTIVES: The goal of this study was to assess the effect of coronary artery diameter on luminal attenuation and the correlation between the transluminal attenuation gradient (TAG) and transluminal diameter gradient (TDG) on computed tomography (CT) coronary angiography. BACKGROUND: Recent studies have reported promising results of TAG in detecting significant stenosis. However, because of the intrinsic nature of CT reconstruction algorithms, luminal attenuation may be affected by vessel diameter. METHODS: In this 3-part study, phantom simulating vessels of various diameters immersed in different contrast mixtures were scanned, and intraluminal attenuations were measured. In addition, dynamic volume CT scanning was performed in 3 mongrel dogs (untreated, a stenosis model, and an occlusion model) using 320-row area detector computed tomography and intraluminal attenuations, and TAGs were calculated at each temporal scan and compared. In a separate clinical study, TAGs and TDGs of 152 coronary arteries from 62 patients who underwent 320-row area detector computed tomography coronary angiography and invasive angiography were measured and compared. RESULTS: Intraluminal attenuation of phantom vessels gradually decreased along with a decrease in diameter. Animal studies revealed that the peak attenuation of distal smaller coronary arteries did not reach that of proximal larger coronary arteries: 55.2% to 78.1% peak attenuation of proximal coronary arteries. No differences in TAG were found between stenotic and normal left circumflex arteries at temporal scans (all, p > 0.05). The clinical study demonstrated significant correlation between TAG and TDG (r = 0.580; p < 0.0001). CONCLUSIONS: Intraluminal attenuation was shown to decrease with diminution of vessel diameters. In addition, TAG exhibited a significant correlation with TDG, implying that TAG may be a secondary result because of differences in diameters. PMID- 27372018 TI - Clinical Utility of Combined FDG-PET/MR to Assess Myocardial Disease. PMID- 27372019 TI - CT Imaging of Bicuspid Aortic Valve Disease for TAVR. PMID- 27372020 TI - Temporal Change in CAC Score and Prognosis: Follow-Up Score Is Simpler and as Good as a Change in Score. PMID- 27372021 TI - Using Imaging to Identify the High-Risk Diabetic Patient: Are We Any Closer? PMID- 27372023 TI - Progression of CAC Score and Risk of Incident CVD. AB - OBJECTIVES: The authors sought to determine the relative contributions of baseline coronary artery calcification (CAC), follow-up CAC, and CAC progression on incident cardiovascular disease (CVD). BACKGROUND: Repeat CAC scanning has been proposed as a method to track progression of total atherosclerotic burden. However, whether CAC progression is a useful predictor of future CVD events remains unclear. METHODS: This was a prospective observational study of 5,933 participants free of CVD who underwent 2 examinations, including CAC scores, and subsequent CVD event assessment. CAC progression was calculated using the square root method. The primary outcome was total CVD events (CVD death, nonfatal myocardial infarction, nonfatal atherosclerotic stroke, coronary artery bypass surgery, percutaneous coronary intervention). Secondary outcomes included hard CVD events, total coronary heart disease (CHD) events, and hard CHD events. RESULTS: CAC was detected at baseline in 2,870 individuals (48%). The average time between scans was 3.5 +/- 2.0 years. After their second scan, 161 individuals experienced a total CVD event during a mean follow-up of 7.3 years. CAC progression was significantly associated with total CVD events (hazard ratio: 1.14, 95% confidence interval: 1.01 to 1.30 per interquartile range; p = 0.042) in the model including baseline CAC, but the contribution of CAC progression was small relative to baseline CAC (chi-square 4.16 vs. 65.92). Furthermore, CAC progression was not associated with total CVD events in the model including follow-up CAC instead of baseline CAC (hazard ratio: 1.05, 95% confidence interval: 0.92 to 1.21; p = 0.475). A model that included follow-up CAC alone performed as well as the model that included baseline CAC and CAC progression. CONCLUSIONS: Although CAC progression was independently, but modestly, associated with CVD outcomes, this relationship was no longer significant when including follow-up CAC in the model. These findings imply that if serial CAC scanning is performed, the latest scan should be used for risk assessment, and in this context, CAC progression provides no additional prognostic information. PMID- 27372022 TI - A Bicuspid Aortic Valve Imaging Classification for the TAVR Era. AB - OBJECTIVES: This study sought to evaluate transcatheter aortic valve replacement (TAVR) in bicuspid aortic valve (BAV) aortic stenosis (AS), with a particular emphasis on TAVR-directed bicuspid aortic valve imaging (BAVi) of morphological classification. BACKGROUND: TAVR has been used to treat BAV-AS but with heterogeneous outcomes and uncertainty regarding the relevance of morphology. METHODS: In 14 centers in the United States, Canada, Europe, and Asia, 130 BAV-AS patients underwent TAVR. Baseline cardiac computed tomography (CT) was analyzed by a dedicated Corelab. Outcomes were assessed in line with Valve Academic Research Consortium criteria. RESULTS: Bicommissural BAV (vs. tricommissural) accounted for 68.9% of those treated in North America, 88.9% in Europe, and 95.5% in Asia (p = 0.003). For bicommissural bicuspids, non-raphe type (vs. raphe type) BAV accounted for 11.9% of those treated in North America, 9.4% in Europe, and 61.9% in Asia (p < 0.001). Overall rates of 30-day mortality (3.8%) and cerebrovascular events (3.2%) were favorable and similar among anatomical subsets. The rate of new permanent pacemaker insertion was high (26.2%) and similar between balloon-expandable (BE) and self-expanding (SE) designs (BE: 25.5% vs. SE: 26.9%; p = 0.83); there was a trend to greater permanent pacemaker insertion in BE TAVR in the presence of coronary cusp fusion BAV morphology. Paravalvular aortic regurgitation (PAR) >= moderate was 18.1% overall but lower at 11.5% in those with pre-procedural CT. In the absence of pre-procedural CT, there was an excess of PAR in BE TAVR that was not the case in those with a pre procedural CT; SE TAVR required more post-dilation. Predictors of PAR included intercommissural distance for bicommissural bicuspids (odd ratio [OR]: 1.37; 95% confidence interval [CI]: 1.02 to 1.84; p = 0.036) and lack of a baseline CT for annular measurement (OR: 3.03; 95% CI: 1.20 to 7.69; p = 0.018). CONCLUSIONS: In this multicenter study, TAVR achieved favorable outcomes in patients with pre procedural CT, with the exception of high permanent pacemaker rates for all devices and shapes. PMID- 27372024 TI - Massive gastrointestinal bleeding in AIDS patients secondary to histoplasma and cytomegalovirus infection. AB - INTRODUCTION: The Cytomegalovirus (CMV) is a virus that affects the host and remains latent. When cellular immunity is suppressed, the virus is reactivated and can cause an asymptomatic or devastating infection in immunosuppressed patients. On the other hand, Histoplasmosis is typically a respiratory condition. However, in immunosuppressed patients, it may be found in unusual locations, as in the case of an intestinal condition. In some cases, this can be fatal. Small intestine CMV location is extremely rare. CASE PRESENTATION: 40-year-old man with AIDS presenting secondary massive lower gastrointestinal bleeding (MLGB) symptoms and ulcer granulomatous injuries located in the proximal ileum produced by the association of CMV and histoplasmosis. CONCLUSION: Lower gastrointestinal bleeding diagnosis and treatment pose a challenge, considering the intestine extension and difficulties for its exploration. On the other hand, the association between Histoplasmosis and CMV as a massive gastrointestinal bleeding cause has not been described. There is no bibliography on the matter. PMID- 27372025 TI - Spontaneous breast cancer remission: A case report. AB - INTRODUCTION: Spontaneous breast cancer remission is a rare phenomenon. We report the disappearance from the remaining breast of a new primary carcinoma that had been confirmed through cytology of a pathological specimen, in a case that is strongly suspected to be spontaneous remission. PRESENTATION OF CASE: A 44-year old woman underwent breast-conserving surgery for a tumor located on the border between the upper-outer and lower-outer quadrants of the left breast (T2, N1, M0; Stage IIB). Eleven years after surgery, computed tomography indicated a mass in the upper-inner quadrant of the left breast. Excisional biopsy was initially planned for treatment following the definitive diagnosis because cytology revealed malignancy. The patient had noticed tumor regression one month after fine-needle aspiration and repeat ultrasonography performed the day before excisional biopsy confirmed the tumor reduction. On pathological examination, no tumor cells were observed in the mass. DISCUSSION: There was a discrepancy between FNA cytology and pathological diagnosis in our patient. The cytological findings indicated malignancy, but the pathological findings did not. When a tumor's pathological diagnosis is not malignant even though its FNA cytology diagnosis was malignant, sampling error, cytological over-diagnosis or some other error may have occurred. In this case, however, these were not detected. Because fibrosis was visible on pathological examination, we believe that these events corresponded to spontaneous remission. CONCLUSION: We report a rare case of spontaneous remission in which the cancer disappeared on pathological examination although the cytological diagnosis had been malignant. PMID- 27372026 TI - Malignant chondroid syringoma in a West African cancer institute: A case report. AB - OBJECTIVE: To report a case of malignant chondroid syringoma, a rare skin tumor at Joliot Curie Cancer Institute in Dakar. RESULTS: We report a case of malignant chondroid syringoma of the deltoid and axilla in a 53year old patient. Malignant chondroid syringoma is an extremely rare tumor of the sweat glands. It is included in myoepithelial tumors of the skin. It has an epithelial component with eccrin or apocrin differentiation, and myoepithelial component. It preferentially seat at the extremities. We report an unusual case with deltoid presentation and axillary mass masqueriding as metastatic lymph node. Surgery is the main treatment. It has a poor prognosis. PMID- 27372027 TI - Psoas muscle abscess simulating acute appendicits: A case report. AB - INTRODUCTION: Psoas abscess is a rare clinical entity with vague symptomatology. We report a psoas abscess that simulated symptoms of acute appendicitis. PRESENTATION OF CASE: A twenty-five year old male presented pain irradiating to the right iliac fossa and lumbar region associated with thigh flexion. Laboratorial exams revealed leukocytosis with a neutrophil shift to the left. Abdominal Ultrasound showed significant intestinal distension and a small quantity of free fluid at the right iliac fossa. Laparotomy and an appendectomy were performed. During immediate post-operative, the patient evolved with worsening of the pain and the leukocytosis, therefore, we chose to maintain his antalgic posture. An abdominal Computerized Tomography scan with contrast was solicited, revealing an increase of the iliac and psoas muscles of the right side, and multiple bacterial focuses. A retroperitoneal access was performed and 300ml of purulent secretion was drained. Afterwards, we implanted a Penrose Drain. The patient had a good post-op evolution, being discharged 7days after the drainage. DISCUSSION: The psoas muscle is a flexor of the thigh. Psoas abscess is an underdiagnosed condition, its main treatment is surgery associated with antibiotic therapy. CT scan seems to be the best choice of diagnostic image exam, although some authors prefer the nuclear magnetic resonance. CONCLUSION: The psoas muscle abscess is uncommon and poorly characterized in its etiology, clinical associations, and its therapeutic approach. On the other hand, acute appendicitis is the most common abdominal emergency, with a 7% death rate, and surgery is its main treatment. PMID- 27372028 TI - Stoppa approach for intrapelvic damage control and reconstruction of complex acetabular defects with intra-pelvic socket migration: A case report. AB - INTRODUCTION: Failed hip arthroplasty with intrapelvic acetabular migration can be challenging due to the potential damage of intrapelvic structures. PRESENTATION OF THE CASE: We present a case of a 75 year-old lady with failed hip arthroplasty with loosening of implants and intra-pelvic migration of the cup, antiprotrusio cage mesh, screws and plate. A modified Stoppa approach was performed, a part of the migrated elements were safely removed, the intrapelvic structures were controlled, and the bone defect was reconstructed through the Stoppa approach combined with the lateral window of ilioinguinal approach by means of bone struts and metallic plates, which is a novel technique. Then an extended posterolateral hip approach was done and the acetabulum was reconstructed using porous tantalum augments and morselized allograft. A cemented constrained socket was implanted. After one-year follow-up the patient is able to walk with one crutch without pain. DISCUSSION: Due to intrapelvic migration, the implants used in hip arthroplasty may become entrapped between the anatomical structures lodged in the pelvis and cause damage to them. A careful preoperative assessment and planning are mandatory. A migrated socket can be inaccessible through a conventional hip approach and removal could be very difficult and dangerous. CONCLUSION: The Stoppa approach in hip revision surgery can be a complement to traditional approaches to control the intrapelvic structures, remove migrated implants of previous surgery and reconstruct the pelvic defect. PMID- 27372029 TI - Testicular seminoma metastasis to duodenum. Misdiagnosed as primary duodenal tumor. AB - INTRODUCTION: Testicular cancer is the most common malignancy in Males aged 15-35 years. Its incidence comprises 0.8% of all Male cancers worldwide, with a mortality rate of 0.1%. Rarely it metastasizes to the retroperitoneum and invades upper gastrointestinal tract (GIT). Complications like intestinal obstruction, hemorrhage, and perforation are usually present. PRESENTATION OF CASE: We report a 30 year-old male, presented to GIT unit with severe anemia due to upper GIT bleeding. Esophagogastroduodenoscopy (OGD) documented duodenal growth. Histopathology findings of biopsy taken from the growth revealed, moderately differentiated adenocarcinoma of duodenum. Abdominal computed tomogram (CT) scan showed retroperitoneal mass which could be primary duodenal tumor or para - aortic lymph node. The patient was referred to surgery unit for pancreatico - duodenectomy with the diagnosis of primary duodenal malignancy. In Surgery unit, a left testicular mass was discovered. Ultrasound revealed suspicious mass in left testis. Review of duodenal biopsy (by another pathologist) was asked for. Duodenal metastatic seminoma was the diagnosis which was confirmed by immunohistochemical Stains (that was not done before). Left testicular biopsy showed testicular seminoma .Patient was treated by high inguinal orchiectomy followed by chemotherapy. One year, later the patient had no GIT symptoms, was not anemic and started to put on weight. Follow up endoscopy showed no evidence of tumor in duodenum. There was no evidence of retroperitoneal growth by follow up CT scan. DISCUSSION: Testis lymphatic drainage is through para aortic lymph nodes .These are in contact with GIT. When testicular malignancy metastasizes to retroperitoneum it may invade GIT causing confusion whether symptoms are primarily from GIT, or they are primarily extra intestinal. CONCLUSION: High index of suspicion for testicular seminoma must be raised when treating young males with GIT complications like hemorrhage. Testicular seminoma is the most common solid tumor at this age. Sometimes it is the cause behind this complication. PMID- 27372030 TI - Omental patch reinforced with polypropylene mesh and split-thickness skin grafting: A new procedure to close the "open abdomen". AB - INTRODUCTION: The "open abdomen" expression widely used to define a full thickness defect of the abdominal wall intentionally made in some situations like abdominal compartment syndrome, has been replaced by a newest one called "laparostomy". The definitive closure of an open abdomen with a giant full abdominal thickness defect remains a problem. CASE REPORT: We present a 67-year old male with a descompressive laparostomy treated with a greater omentum flap sutured hermetically with interrupted stitches at the edges of the muscle wall, reinforced with large mesh of polypropylene (PP) placed on-lay and sutured to the fascia by two concentric running sutures of polypropylene. A vacuum-assisted closure device was placed on the second postoperative day and it was kept during three weeks. By then the PP mesh was completely integrated so skin grafts were applied to the surface of the granulation tissue. An incisional hernia was easily repaired at three years of follow-up. Eight months after the last surgery the patient is satisfied with the result achieved. DISCUSSION: The great omentum has immunological and angiogenic properties that allow a rapid integration of the polypropylene mesh, even in septic environments, facilitating the engraftment of split-thickness skin graft. The reactive fibrosis caused by the PP mesh replaces the fat tissue but the inner surface is preserved, thereby avoiding subsequent adhesion and facilitates surgical access to the abdominal cavity if necessary in the future. CONCLUSION: The structure achieved is a strong structure, capable of visceral isolation that can be useful to close some OA. PMID- 27372031 TI - Looking for sufficient change: Evaluation of counsellor training for STI syndromic management in India. AB - In India, public health care of Sexually Transmitted Infections is delivered through Designated STI/RTI Clinics (DSRCs) using syndromic management. This paper describes efforts, over three years, to improve in-service training for counsellors positioned at DSRCs-using a data approach. The programme managers realised, through rigorous monitoring of initial induction training reports that, while knowledge and attitudes of most trainees had improved as evident from t tests, at least one-quarter scored worse on post-training assessments (n=859). Therefore, they undertook a survey using a competency approach to diagnose what critical competencies are influenced through training: counselling skills, risk reduction suggestions, labelling male and female anatomy, record-keeping and STI patient education (n=132). Survey results demonstrated that trainees failed to pass a two-thirds cutoff score in most competencies. These findings led the programme managers to modify training and implement tighter quality measures. In the second round of training - refresher training - outcomes on competency assessments before and after training showed more acceptable performance (n=833). The paper describes how programme managers, after an acceptance of such initial short-comings, developed customized assessments when literature provided limited guidance and how they worked to achieve change that was acceptable for programme needs. PMID- 27372032 TI - Editorial overview: Host-microbe interactions: parasites: How eukaryotic parasites meet the challenges of life in a host. PMID- 27372033 TI - Esophago-jejunal anastomosis after laparoscopic total gastrectomy. PMID- 27372034 TI - Comments on " Emergency laparoscopy: Role and implementation " Journal de Chirurgie Viscerale (2015) 152, S12-S19. PMID- 27372035 TI - Pyopneumothorax and peritonitis due to perforated duodenal ulcer and associated pleuroperitoneal communication. AB - Pleuroperitoneal communication is an anatomic entity that is typically asymptomatic but sometimes responsible for hydrothorax. This pleural manifestation can be explained by progressive transdiaphragmatic passage of intra abdominal fluid because of abdominal hyperpressure. The object of this report is to present a hitherto unreported association of concomitant pleural effusion and acute infectious abdominal disease, due to perforated duodenal ulcer. This underscores that pleural effusion associated with acute abdominal pain may reveal the existence of a communication of this type, and requires surgical management. PMID- 27372036 TI - Atrial tissue expression of receptor for advanced glycation end-products (RAGE) and atrial fibrosis in patients with mitral valve disease. AB - BACKGROUND: It has been reported that receptor for advanced glycation end products (RAGE) plays a significant role in cardiac fibrosis. Nonetheless, the precise relationship between the RAGE and atrial fibrosis has never been studied in humans. The aim of this study was to determine whether degree of atrial fibrosis was associated with atrial tissue expression of RAGE in patients with mitral valve disease (MVD). METHODS: We collected human left atrial (LA) appendage tissue from 25 patients who underwent mitral valve surgery. We quantified the expression of RAGE and other protein markers by Western blotting and compared these levels with histological evaluations. RESULTS: RAGE expression in the LA appendage tissue was significantly correlated with atrial fibrosis (r=0.681, p=0.001). RAGE expression (regression coefficient [B] 9.49, 95% confidence interval [CI] 4.76-14.2, p<0.001) and LA diameter (B 0.43, 95% CI 0.13 0.74, p=0.008) were independently associated with degree of atrial fibrosis in multiple linear regression analysis. RAGE expression was significantly correlated with protein expression of von Willebrand factor (r=0.659, p<0.001), vascular endothelial cadherin (r=0.757, p<0.001), ICAM-1 (r=0.568, p=0.003), and PECAM-1 (r=0.423, p=0.035) in the LA appendage tissue. In addition, patients with severe mitral stenosis (MS) had higher atrial RAGE expression than those with no, mild, or moderate MS (p=0.013). Patients with MVD and atrial fibrillation (AF) had more severe atrial fibrosis (p=0.024) and higher RAGE expression (p=0.047) than those who remained in sinus rhythm. CONCLUSIONS: Atrial tissue expression of RAGE was significantly associated with atrial fibrosis, severe MS, and AF rhythm in patients with MVD. PMID- 27372037 TI - Short and long-term outcomes of alcohol septal ablation with the trans-radial versus the trans-femoral approach: A single center-experience. AB - BACKGROUND: Although the trans-radial approach (TR) has been applied to various subsets of patients in percutaneous coronary intervention, the feasibility, efficacy, acute procedural and long-term outcomes of TR versus trans-femoral approach (TF) for alcohol septal ablation (ASA) have not yet been determined. OBJECTIVES: The aim of this study was to compare the short and long-term outcomes of ASA with the TR approach compared to the TF approach. METHODS: We retrospectively analyzed 240 patients who underwent an ASA procedure at our institution from November 1999 to November 2015. The TR approach was performed in 172 cases and the TF approach in the remaining 68 cases. RESULTS: The use of TR approach progressively increased from 62% in 1999-2005 to 91% in 2011-2015 (p=0.0001). The TF and TR group had similar age, baseline NYHA class (NYHA 3 or 4) and mean left ventricular outflow tract peak gradient before ASA. Total contrast used (TR: 73.2+/-47.2ml; TF: 88.7+/-49.3ml, p=0.11), total radiation Air kerma area product (TR: 43.7+/-48.0Gycm(-2); TF: 55.9+/-48.2Gycm(-2); p=0.39) and peak left ventricular outflow tract gradient immediately after ASA (TR: 19.1+/ 19.6mmHg; TF: 20.4+/-18.0mmHg, p=0.63) were similar in both groups. Procedural success was 91.9% and 91.2% in the TR and TF groups, respectively (p=0.53). At 30days, there was 2 intra-hospital death (1 in TF and 1 in TR), 1 major stroke in the TF group and 1 coronary artery dissection in the TR group. Vascular complications were less frequent in the TR group (0.58% vs. 7.3%; p=0.002). The mean length of follow-up was 4.56+/-4.34years (IQR 0.69-8.2; median 2.92years; maximum: 15.5years). By Kaplan-Meier estimate, the observed survival in the overall cohort was comparable to the expected survival for a sex and age-matched comparable general French population at 10years (86.9 vs. 83.6%, p=0.88). Survival was similar between the TR and TF group (92.1% vs. 89.7% at 6years, respectively; p=0.71). CONCLUSIONS: Alcohol septal ablation from the radial approach can be performed with similar acute and long-term success, but with lower vascular complications compared to the femoral approach. PMID- 27372038 TI - A brief review on the mechanisms of aspirin resistance. AB - Aspirin is the most widely prescribed drug for the primary and secondary prevention of cardiovascular and cerebrovascular diseases. However, a large number of patients continue to experience thromboembolic events despite aspirin therapy, a phenomenon referred to as aspirin resistance or treatment failure. Aspirin resistance is often observed along with a high incidence of unstable plaque, cardiovascular events and cerebrovascular accident. Studies have shown that aspirin reduces the production of TXA2, but not totally inhibits the activation of platelets. In this review, we analyze current and past research on aspirin resistance, presenting important summaries of results regarding the potential contributive roles of single nucleotide polymorphisms, inflammation, metabolic syndrome and miRNAs. The aim of this article is to provide a brief review on aspirin resistance and platelet function, which will provide important insights into the research of aspirin resistance. PMID- 27372039 TI - ECG predictors of T wave oversensing in subcutaneous implantable cardioverter defibrillators. AB - BACKGROUND: T wave oversensing (TWOS) is the commonest cause of inappropriate shocks in subcutaneous implantable cardioverter defibrillators (S-ICDs). We hypothesise that predictors of TWOS can be derived from surface ECG parameters. METHODS: In a cohort of SICD recipients in two UK centres, all patients who had TWOS (study group) were compared to all those who had not (control group). The pre-implant screen was scanned and the R wave, T wave amplitudes, QRS interval, time to peak T wave, QT interval and R:T ratio was measured using digital callipers. Logistic regression was performed to identify ECG predictors of TWOS. RESULTS: One hundred one patients were studied. Six (5.9%) had TWOS. The mean age of the population was 58.6+/-18years and the median follow-up was 19.5months. By univariate analysis, the predictors of TWOS are QRS duration (140.7+/-28.7 vs. 105.9+/-24.6, P=0.007), time to peak T wave (corrected for heart rate, pTc) (403.9+/-22.6 vs. 347.8+/-41.4, P=0.006), QTc interval (500.4+/-41.2 vs. 446.8+/ 49.7, P=0.021), and R:T ratio (3.5+/-1.1 vs. 9.5+/-13.2, P=0.034). By multivariate analysis, time to pTc is the most predictive of TWOS. A time to pTc of 390ms cut-off point provided a sensitivity 38.5%, a specificity of 98.9%, a positive predictive value for TWOS of 83.3%, and a negative predictive value of 91.6% (AUC=0.687). CONCLUSION: In this study, time to pTc is the most powerful ECG predictor of TWOS. PMID- 27372040 TI - Prevalence of parameters of suboptimal scaffold deployment following angiographic guided bioresorbable vascular scaffold implantation in real world practice - an optical coherence tomography analysis. AB - AIM: To assess the prevalence of suboptimal bioresorbable vascular scaffold (BVS, Abbott Vascular, Santa Clara, California) deployment in real world practice with intracoronary optical coherence tomography (OCT) imaging. METHODS: Consecutive patients who underwent percutaneous coronary intervention using BVS and the final optimization assessed with OCT imaging in two tertiary care centers between December 2012 and February 2015 were evaluated for parameters of suboptimal scaffold deployment by OCT. RESULTS: Overall, 36 scaffolds were implanted in 27 patients during this period. Mean age of the population was 54.7+/-8.2years and 19 (70.4%) were type B2/C lesions. The prevalence of parameters of suboptimal scaffold deployment were: underexpansion-22(61.1%), geographic miss-3(8.3%), tissue prolapse-7(25.9%), scaffold pattern irregularity-1(2.8%), longitudinal elongation-7(38.8%). Of the 7 overlaps imaged: excessive overlap was observed in 3 and scaffold gap in one. The median duration of follow up was 679days (range 193-963days). There were four events during this period. None were associated with suboptimal scaffold deployment. CONCLUSION: OCT based parameters of suboptimal scaffold deployment are common in real world scenario and were not associated with adverse outcomes on long term follow up. These findings need to be confirmed in larger studies. PMID- 27372041 TI - Familial non-syndromal thoracic aortic aneurysms and dissections - Incidence and family screening outcomes. AB - BACKGROUND: Non-syndromal thoracic aortic aneurysm and dissection (ns-TAAD) is a genetic aortopathy, with uncertain incidence. This study documented the incidence of ns-TAAD and outcomes of family screening over 15years. METHODS: Consecutive series of 2385 patients with aortic disease in prospective registry (2000 to 2014), including 675 undergoing surgery. Diagnosis of ns-TAAD included family history, aortic imaging, tissue pathology and mutation testing. Screening was offered to relatives of ns-TAAD probands, with follow-up for affected individuals. RESULTS: There were 270 ns-TAAD probands (74% males), including 116 (43%) presenting with aortic dissection. Among surgical cases, a diagnosis of ns TAAD was established for 116 (17%). Age of probands was 50.4+/-14.1years, with aortic diameter of 51+/-12mm. Screening of 581 at-risk relatives identified 216 new ns-TAAD cases (detection rate=37%). Among 71 probands with known family history, screening identified 130 new affected relatives and among 53 probands with no family history, screening identified 86 new affected relatives. Mean age of new affected relatives at diagnosis was 44+/-18years, with aortic diameter of 42+/-7mm, including 42 with diameter>50mm. Ten-year mortality was similar for probands without dissection (7.7+/-3.1%) and new affected relatives (11.4+/-4.0%) but greater for probands surviving initial dissection (27.6+/-7.8%, p=0.003). CONCLUSIONS: Up to 1 in 6 patients undergoing aortic surgery have features of ns TAAD, frequently presenting as aortic dissection but at later age than other genetic aortopathies. Family screening identifies affected relatives in up to half of ns-TAAD probands, many of whom already have significant aortic dilatation. PMID- 27372042 TI - Elevated levels of triglycerides and vldl-cholesterol provoke activation of nlrp1 inflammasome in endothelial cells. AB - BACKGROUND: Soluble stimuli present in the plasma of patients with peripheral arterial disease (PAD) are capable of directly stimulating intracellular signalling in endothelium. Oxidized-LDL (oxLDL) induces NLRP3 inflammasome activation in macrophages. However, it is not clear how lipid profile affect NLRP1 inflammasome gene expression in endothelial cells. In this study, the effect of cholesterol and TG of plasma of patients with PAD on NLRP1 inflammasome gene expression in human arterial endothelial cells (HAECS) was assessed. METHODS: We included 113 patients with symptomatic PAD. HAECs were stimulated for 2h using the plasma samples of the study participants. The NLRP1 quantification of the transcription was carried out on the 7500 real-time PCR system using the Taqman(r) Universal PCR Master Mix and Assays on demand. Relative quantification of the NLRP1 expression was carried out using the DeltaDeltaCt (threshold cycle) comparative method. RESULTS: Plasma from patients with elevated VLDL-cholesterol levels (>33.6mg/dL, the median value of the sample) provoked a higher expression of NLRP1 inflammasome in HAECs (RQ=1.15+/-0.23 vs. 1.05+/-0.69; p=0.045), as well as plasma from patients with elevated TGs levels (>168mg/dL, the median value of the sample) (RQ=1.15+/-0.23 vs. 1.05+/-0.69; p=0.045). A positive correlation was found between NLRP1 inflammasome expression and VLDL-cholesterol plasma levels (r=0.4; p<0.001) as between NLRP1 inflammasome expression and TG levels (r=0.4; p<0.001). CONCLUSIONS: Plasma TG and VLDL cholesterol of patients with atherosclerosis, manifested as PAD, promote the in vitro NLRP1 inflammasome expression in HAECs. PMID- 27372043 TI - Association between long-term prescription of aldosterone antagonist and the progression of heart failure with preserved ejection fraction in hypertensive patients. AB - BACKGROUND: Hypertension complicated with left ventricular hypertrophy (LVH) and diastolic dysfunction is independently related to increasing risk of subsequent incident heart failure with preserved ejection fraction (HFpEF). This study was designed to evaluate the influences of long-term aldosterone antagonist prescription in these patients. METHODS: Using a propensity score matching of 1:2 ratio, this retrospective claims database study compared spironolactone prescription (n=65) and non-spironolactone therapy (n=130) in hypertensive patients with LVH [left ventricular mass index (LVMI)>125g/m(2) for men and >110g/m(2) for women] and suspected diastolic dysfunction (E/E' ratio between 8 and 15) and without clinical signs or symptoms of heart failure. RESULTS: With a median follow-up of 7.4years, the new-onset symptomatic HFpEF occurred in 3 of 65 patients in the spironolactone group and 21 of 130 patients in the non spironolactone group (P=0.021). Spironolactone also generated more prominent improvement in diastolic function and LVH. And multivariate logistic regression model revealed that spironolactone prescription (OR 0.177, 95% CI: 0.045-0.687, P=0.012) was associated with a reduced risk of new onset of symptomatic HFpEF, and the elevation of LVMI (OR 1.053, 95% CI: 1.011-1.097, P=0.012) or E/E' (OR 1.280, 95% CI: 1.015-1.615, P=0.037) was associated with a high risk of new onset of symptomatic HFpEF. CONCLUSIONS: Long-term aldosterone antagonist exposure was associated with protective effects in terms of the incidence of new-onset symptomatic HFpEF, LV diastolic dysfunction and LVH in hypertensive patients, which might be beneficial for the delay of HFpEF progression. PMID- 27372044 TI - Advanced research on the microRNA mechanism in heart failure. AB - Heart failure is the end stage of most cardiac diseases and also an important cardiovascular disease. Ventricular remodeling, a complicated pathophysiological process involving multiple molecular pathways, is a crucial mechanism for the occurrence and development of heart failure. A microRNA (miRNA) is a highly conservative noncoding molecule containing 18-25 nucleotides. miRNA is different from other RNAs. It mainly serves as an endogenous gene-regulating factor, and is a member of the complex regulatory network. It induces gene repression of target transcripts by affecting mRNA at the post-transcriptional level Vasudevan et al. (2007) . This study aimed at determining the mechanism of miRNA action in heart failure. PMID- 27372045 TI - Management of coronary artery aneurysms using abciximab in children with Kawasaki disease. AB - INTRODUCTION: There are limited data regarding the possible benefits of abciximab in children with Kawasaki disease (KD), who developed serious cardiac abnormalities non-responsive to standard treatment. MATERIALS AND METHODS: We retrospectively identified children with KD who were treated with abciximab from 2007 to 2015. Data regarding clinical course, treatment, echocardiographic data and follow-up at 1 and 6months were retrieved. RESULTS: During the study period, fifteen children were identified who were diagnosed with KD and were given abciximab. The median age at onset of symptoms was 11months (range: 2months 6years). The median day of disease at admission was 10days (range: 4-26days) and the median day of administration of abciximab was 17days (range: 9-40). Twelve children were diagnosed with complete and three with incomplete KD. Aneurysms were found in 8 children: 2 had ectatic coronary arteries and 5 presented with both ectasia and aneurysms. At 1month follow-up, echocardiographic findings showed regression in the size of aneurysms in 11 children, resolution of the aneurysms or ectasia of coronary arteries in 3 children, while one child who could not take aspirin because of G6PD deficiency died. After 6months of follow up, echocardiographic findings showed resolution of coronary abnormalities in 12 (80%) children, whereas 2 children (13.3%) presented with significant regression of aneurysms. CONCLUSIONS: Abciximab may have an important role in the management of severe cardiac complications of KD, although prospective randomized controlled studies are needed to fully evaluate its role. PMID- 27372046 TI - Recurrence, lingering recovery course, mild variants, and "chronic" forms, of takotsubo syndrome. PMID- 27372047 TI - On-admission high endothelin-1 level independently predicts in-hospital adverse cardiac events following ST-elevation acute myocardial infarction. PMID- 27372048 TI - Is elite sport activity associated with specific supranormal left ventricular contractility? (Insights from the three-dimensional speckle-tracking echocardiographic MAGYAR-Sport Study). PMID- 27372049 TI - Prevalence of aortic valve dystrophy and insufficiency in a cohort of 255 HIV positive patients followed-up in a cardiology department between 2012 and 2014. AB - OBJECTIVES: To study valve appearance and the presence of valve disease in a cohort of people living with HIV (PLHIV). DESIGN: A prospective study of PLHIV examined at the cardiology department of the Clermont Ferrand university hospital group (CHU) between January 1, 2012, and December 31, 2014. Were excluded those with a history of infection associated with a possible endocarditis. METHODS: Demographic, medical characteristics and cardiovascular disease risk factors at time of cardiovascular examination and Doppler-echocardiography were recorded and analyzed. RESULTS: In total, 903 PLHIV were examined in the infectious diseases department, 255 of whom were included. These consisted of 67 women (26.3%) and 188 men, of a mean age of 51.2+/-9.7years, in whom coronary artery disease was diagnosed in 18 patients (7.0%), two women and 16 men, representing a prevalence of 3.0% in females and 8.5% in males. The appearance of the aortic cusps was considered dystrophic in 14.1% of cases (36/255), dysplastic in two cases (0.8%), exhibiting a bicuspid deformity in one case. The prevalence of aortic valve abnormality was therefore 6.0% in the women (4/67) and 17.0% in the men (32/188). On facing off this data with the Kora Monica study findings, an increase in prevalence appears only to truly manifest after 50years of age. We registered 35 aortic insufficiency cases (13.7%), representing a higher incidence than that of the Framingham cohort, with age and masculine gender being the determining factors. CONCLUSION: Valve disease, along with coronary artery disease, should be closely monitored in PLHIV. PMID- 27372050 TI - The impact of renal sympathetic denervation on cardiac electrophysiology and arrhythmias: A systematic review of the literature. AB - INTRODUCTION: Increased central sympathetic activity has a central role in the pathophysiology of cardiac arrhythmias. Despite the recently published negative results regarding the impact of renal sympathetic denervation (RDN) on resistant hypertension treatment, the beneficial effects of this intervention on cardiac arrhythmias seems to be promising. The aim of this systematic review is to analyze the existing data regarding the impact of RDN on atrial and ventricular arrhythmias. METHODS: We systematically searched MEDLINE/PubMed database until January 2016 by using the algorithm "renal denervation AND (arrhythmias OR atrial OR ventricular)" without limitations. Additionally, the reference lists of the included studies and the relevant review studies were also manually searched. RESULTS: Of the 467 studies yielded from the initial search, 34 were finally included in the systematic review (15 human studies, 18 animal studies and 1 study with both experimental and clinical data). The critical analysis of data from both human and animal studies indicates that RDN can modulate atrial and ventricular electrophysiological properties and exerts favorable effects in the development and recurrence of atrial and ventricular arrhythmias. CONCLUSION: In this systematic review we showed that RDN reduces the burden of atrial and ventricular arrhythmias in various experimental and clinical settings. Appropriately designed randomized sham controlled trials are needed in order to elucidate the exact impact of RDN on arrhythmia management. PMID- 27372051 TI - Prediction of atrial fibrillation in patients with supraventricular tachyarrhythmias treated with catheter ablation or not. Classical scores are not useful. AB - BACKGROUND: Atrial fibrillation (AF) and other supraventricular tachyarrhythmias (SVTA) [atrial flutter (AFL), atrioventricular nodal reentrant tachycardia (AVNRT), atrioventricular reentrant tachycardia (AVRT) and preexcitation syndrome (PS)] are frequently associated. We assessed the AF occurrence frequency and predictors according to the nature of SVTA and completion of SVTA ablation. METHODS AND RESULTS: 4169 patients were referred for SVTA (typical AVNRT: 1338, AVRT over a concealed accessory pathway: 329, atypical AVNRT: 205, AFL: 1321; PS: 976); mean age was 50+/-20years; electrophysiological study (EPS) was systematic; patients were followed for a mean duration of 3+/-4.5years. Ablation of SVTA was performed in 2949 patients (71%) and 1220 patients were not treated or treated with antiarrhythmic drugs. AF developed in 469 patients (11.2%). In the multivariable model, AF prior to ablation, history of AF, nature of SVTA (AFL), and presence of heart disease were associated with a high risk of AF during follow-up. Presence of heart failure, old age, diabetes and vascular disease were not predictive of AF. Ablation was a weak but significant factor of AF prevention. A score based on nature of SVTA, presence of heart disease and history of AF is proposed. CONCLUSIONS: AF occurrence in patients with SVTA cannot be predicted by the presence of heart failure, old age, diabetes and vascular disease, but only by the following criteria, presence of heart disease, history of AF and nature of the SVTA (SVTA). PMID- 27372052 TI - Inhibition of cholesterol transport in an intestine cell model by pine-derived phytosterols. AB - We have quantified the inhibition of intestinal cholesterol transport by pine derived phytosterols using an HT29-MTX intestine cell model that forms a mucus layer similar to that in the intestine. An artificial intestinal fluid consisting of digested fat, bile salt, cholesterol, and phytosterols was formulated in order to mimic the conditions in the intestine. The apparent permeability coefficient (Papp) of the positive control, i.e., 0.1mM of cholesterol solubilized in the artificial intestine fluid, was found to be 0.33 (+/-0.17)*10-6cm/s. When 0.1mM beta-sitosterol was solubilized alongside, Papp was effectively zero, corresponding to a total inhibition of cholesterol transport. A similar strong inhibition was found when commercial pine-derived phytosterols, PinVitaTM FSP DuPont, were co-solubilized with cholesterol in the dietary model micelles, leading to Papp=0.06 (+/-0.06)*10-6cm/s, i.e., 5.5 times lower than the cholesterol positive control. Additionally, the effect of potential oral administration formulations generated by the pine-derived phytosterols was also characterized. The formulations were produced as a liquid formulation of the cholesterol-containing artificial intestine fluid. Six liquid formulations were tested of which four displayed a Papp in the range of 0-0.09*10-6cm/s. The remaining two formulations did not show any inhibition effect on cholesterol transport and even enhanced cholesterol transport. It was furthermore observed that the phytosterols were found in the collected intestine cells but not transported to the basolateral region in the intestinal cell model system. PMID- 27372053 TI - Health Care Delivery Practices in Huntington's Disease Specialty Clinics: An International Survey. AB - BACKGROUND: Little is known about the organization of clinical services for Huntington's disease (HD). OBJECTIVE: To describe how health care services are organized and delivered in HD-clinics taking part in or eligible for the Enroll HD study. METHODS: In 2014, a 69-item survey was administered to sites taking part in or eligible for the Enroll-HD study. RESULTS: Of 231 sites surveyed, 121 (52.2%) sites in Europe, North America, Latin America, and Oceania responded. Most sites in the sample serve large populations, with 61.1% serving more than 1.5 million people, and a further 33% serving >500,000. Almost all (86.0%) centers see patients from outside their region. The majority of centers (59.7%) follow 50-199 patients, 21.9% care for more than 200. Most centers provide care in all stages of HD, and nearly all review pre-symptomatic cases. Multidisciplinary case reviews are offered in 54.5% of sites, with outreach clinics offered by 48.1%. Videoconferencing and telemedicine are used by 23.6%. Separate consultations for caregivers are offered in more than half of the centers. Most centers (70.4%) report following published guidelines or local care pathways for HD. CONCLUSIONS: Most centers serve a large population and use a multidisciplinary approach. The survey gives insight into factors underpinning HD service delivery globally. There is a need for more in-depth studies of clinical practice to understand how services are organized and how such features may be associated with quality of care. PMID- 27372055 TI - The role of the human cerebellum in performance monitoring. AB - While the cerebellum has traditionally been thought of as mainly involved in motor functions, evidence has been accumulating for cerebellar contributions also to non-motor, cognitive functions. The notion of a cerebellar internal model underlying prediction and processing of sensory events and coordination and fine tuning of appropriate responses has put the cerebellum right at the interface of motor behavior and cognition. Along these lines, the cerebellum may critically contribute to performance monitoring, a set of cognitive and affective functions underlying adaptive behavior. This review presents and integrates evidence from recent neuroimaging and clinical studies for a cerebellar role in performance monitoring with focus on sensory prediction, error and conflict processing, response inhibition, and feedback learning. Together with evidence for involvement in articulatory monitoring during working memory, these findings suggest monitoring as the cerebellum's overarching function. PMID- 27372054 TI - Induced Pluripotent Stem Cells in Huntington's Disease Research: Progress and Opportunity. AB - Induced pluripotent stem cells (iPSCs) derived from controls and patients can act as a starting point for in vitro differentiation into human brain cells for discovery of novel targets and treatments for human disease without the same ethical limitations posed by embryonic stem cells. Numerous groups have successfully produced and characterized Huntington's disease (HD) iPSCs with different CAG repeat lengths, including cells from patients with one or two HD alleles. HD iPSCs and the neural cell types derived from them recapitulate some disease phenotypes found in both human patients and animal models. Although these discoveries are encouraging, the use of iPSCs for cutting edge and reproducible research has been limited due to some of the inherent problems with cell lines and the technological differences in the way laboratories use them. The goal of this review is to summarize the current state of the HD iPSC field, and to highlight some of the issues that need to be addressed to maximize their potential as research tools. PMID- 27372056 TI - The prevalence and treatment patterns of diabetes in the Greek population based on real-world data from the nation-wide prescription database. AB - AIMS: Epidemiological data regarding diabetes in Greece are based on regional, small-scale studies. We aimed to identify all citizens with prescribed pharmacological treatment for diabetes, to further explore type 1 diabetes prevalence and describe pharmacological treatment patterns in type 2 diabetes. METHODS: The electronic prescription database of the National Organization for Health Care Services Provision was used to identify individuals who received at least two prescriptions with an ICD-10 code relevant to diabetes, dispensed between June 1st, 2014 and May 31st, 2015. Type-1 diabetes was defined in those receiving at least two fully-reimbursable insulin prescriptions with an ICD-10 code of E10 (insulin-dependent diabetes). RESULTS: The study population consisted of 10,222,779 individuals, accounting for 95% of the Greek population. Prevalence of medication-prescribed diabetes was 7.0% (720,764 individuals), ranging from 0.08% in children and adolescents, to 8.2% in adults, and 30.3% in those ?75years old. Prevalence of type 1 diabetes was 0.24%, with a clear male predominance and more than half of cases developing after 14years of age. Metformin was the most frequently prescribed medication (77.4%) in type-2 diabetes followed by DPP-4 inhibitors (44.8%) and sulphonylureas (34.5%), while insulin was used by 19.4% of patients. CONCLUSIONS: This nation-wide real-world data analysis on medication prescribed diabetes demonstrates that the current prevalence in Greece is 7.0%, with wide age variation and high figures in older adults. Identification of pharmacological patterns among patients with type 2 diabetes is a valuable guide in policy-makers' efforts to balance a cost-effective, quality-acceptable disease management. PMID- 27372057 TI - Reporting on cyclist crashes in Australian newspapers. AB - OBJECTIVE: To assess information on cyclist crashes reported in Australian newspapers. METHODS: The Factiva news archive was searched for articles on cyclist crashes published in major Australian newspapers between 2010 and 2013. Information on the circumstances of cyclist crashes were extracted and coded. RESULTS: A total of 160 cyclist crashes were covered by 198 newspaper articles, with 44% of crashes resulting in cyclist fatalities. Crashes reported by more than one newspaper were more likely to involve public figures or protracted court cases. Individual characteristics of cyclists as well as the location of the crash were reported for more than 80% of crashes. The road user at fault was reported for more than half of crashes. In contrast, information on helmet use, alcohol and cycling lanes was mentioned for only about 10% of crashes. Fewer than one in five articles mentioned prevention strategies including education campaigns, legislative and infrastructure changes. CONCLUSION: Australian newspapers tend to focus on the most dramatic and more 'newsworthy' aspects of cyclist crashes. Cycling advocates need to work with journalists to improve the quality of this coverage. IMPLICATIONS: Better communication between cycling advocates and journalists is likely to have a positive impact on the safety and the uptake of cycling in the community. PMID- 27372058 TI - Artemisinin protects human retinal pigment epithelial cells from hydrogen peroxide-induced oxidative damage through activation of ERK/CREB signaling. AB - The pathological increase in the levels of reactive oxygen species (ROS) in the retinal pigment epithelium (RPE), is implicated in the development of age-related macular degeneration (AMD). The discovery of drug candidates to effectively protect RPE cells from oxidative damage is required to resolve the pathological aspects and modify the process of AMD. In this study, a FDA-approved anti-malaria drug, Artemisinin was found to suppress hydrogen peroxide (H2O2)-induced cell death in human RPE cell-D407 cells. Further study showed that Artemisinin significantly suppressed H2O2- induced D407 cell death by restoring abnormal changes in nuclear morphology, intracellular ROS, mitochondrial membrane potential and apoptotic biomarkers. Western blotting analysis showed that Artemisinin was able to activate extracellular regulated ERK/CREB survival signaling. Furthermore, Artemisinin failed to suppress H2O2-induced cytotoxicity and the increase of caspase 3/7 activity in the presence of the ERK inhibitor PD98059. Taken together, these results suggest that Artemisinin is a potential protectant with the pro-survival effects against H2O2 insult through activation of the ERK/CREB pathway. PMID- 27372059 TI - High performance computing for three-dimensional agent-based molecular models. AB - Agent-based simulations are increasingly popular in exploring and understanding cellular systems, but the natural complexity of these systems and the desire to grasp different modelling levels demand cost-effective simulation strategies and tools. In this context, the present paper introduces novel sequential and distributed approaches for the three-dimensional agent-based simulation of individual molecules in cellular events. These approaches are able to describe the dimensions and position of the molecules with high accuracy and thus, study the critical effect of spatial distribution on cellular events. Moreover, two of the approaches allow multi-thread high performance simulations, distributing the three-dimensional model in a platform independent and computationally efficient way. Evaluation addressed the reproduction of molecular scenarios and different scalability aspects of agent creation and agent interaction. The three approaches simulate common biophysical and biochemical laws faithfully. The distributed approaches show improved performance when dealing with large agent populations while the sequential approach is better suited for small to medium size agent populations. Overall, the main new contribution of the approaches is the ability to simulate three-dimensional agent-based models at the molecular level with reduced implementation effort and moderate-level computational capacity. Since these approaches have a generic design, they have the major potential of being used in any event-driven agent-based tool. PMID- 27372060 TI - Clinical significance of post-surgical residual tumor burden and radiation therapy in treating patients with lacrimal adenoid cystic carcinoma. AB - Retrospective analyses were done on 19 lacrimal adenoid cystic carcinoma (ACC) patients who underwent curative treatment between 1997 and 2013. Nine patients (47.4%) had T1-2 disease and ten (52.6%) had T4 disease. Surgical procedures were globe-preserving tumor resection in 11 patients (57.9%), incisional biopsy in five (26.3%), and orbital exenteration was undertaken in three (15.8%). Residual tumor burdens were R0/1 in 12 patients (63.2%) and R2 in seven (36.8%). Radiation therapy (RT) was recommended to all patients, and 16 (84.2%) completed RT (median 60 Gy). After median follow-up of 57.5 months, seven (36.8%) developed progression and three (15.8%) died. Local recurrence occurred in four patients (21.1%), distant metastasis in one (5.3%), and combined local recurrence and distant metastasis in two (10.5%). Progression-free survival and overall survival rates at 5-years were 64.5% and 82.6%, respectively. Among 12 patients following R0/1 resection, two (16.7%) developed local recurrence and none died, while among seven following R2 resection, five (71.4%) developed progression and three (42.9%) died. RT following R0/R1 resection could reduce progression. Globe preserving surgery and RT seemed optimal strategy for T1-2 disease. Careful attention should to be paid to minimize residual tumor burden at surgery and effort for safe radiation dose escalation would be desired. PMID- 27372061 TI - Profiling the mobile-only population in Australia: insights from the Australian National Health Survey. AB - BACKGROUND: The Australian population that relies on mobile phones exclusively has increased from 5% in 2005 to 29% in 2014. Failing to include this mobile-only population leads to a potential bias in estimates from landline-based telephone surveys. This paper considers the impacts on selected health prevalence estimates with and without the mobile-only population. METHODS: Using data from the Australian Health Survey - which, for the first time, included a question on telephone status - we examined demographic, geographic and health differences between the landline-accessible and mobile-only population. These groups were also compared to the full population, controlling for the sampling design and differential non-response patterns in the observed sample through weighting and benchmarking. RESULTS: The landline-accessible population differs from the mobile only population for selected health measures resulting in biased prevalence estimates for smoking, alcohol risk and private health insurance coverage in the full population. The differences remain even after adjusting for age and gender. CONCLUSIONS: Using landline telephones only for conducting population health surveys will have an impact on prevalence rate estimates of health risk factors due to the differing profiles of the mobile-only population from the landline accessible population. PMID- 27372062 TI - Changes in the sexual health behaviours of New Zealand secondary school students, 2001-2012: findings from a national survey series. AB - OBJECTIVE: To describe trends in self-reported sexual and reproductive health behaviours among New Zealand secondary school students. METHODS: Nationally representative health and wellbeing surveys conducted in 2001 (n=9,699), 2007 (n=9,107) and 2012 (n=8,500) were analysed. Logistic regressions were used to explore variations in sexual health outcomes between 2001 and 2012. RESULTS: 'Ever had sex' (-6.9%, p<0.001); 'currently sexually active' (- 2.3%, p<0.001); 'always use condoms' (-3.3%, p=0.006); 'condoms at last sex' (-7.0, p=0.002); 'contraception at last sex' (-5.8%, p<0.001) and sexually transmitted infections (-0.3%, p=0.001) have reduced over time. 'Always use contraception' did not change significantly (-1.4%, p=0.514) over time. Maori (OR 0.7), Pacific (OR 0.5) and socioeconomically deprived students (OR 0.7) less frequently used condoms. Maori (OR 0.6), Pacific (OR 0.4), Asian (OR 0.5), younger (OR 0.6), and socioeconomically deprived (OR 0.6) students less frequently used contraception. CONCLUSIONS: Students in 2012 were more likely to delay sexual activity, but were less likely to use condoms and contraception consistently, compared to students in 2001. Declining contraceptive use over an 11-year period suggests that current strategies are inadequate, particularly for Maori, Pacific and socioeconomically deprived students. Appropriate and accessible sexual and reproductive health services are urgently required. PMID- 27372063 TI - Indoor particulate matter exposure is associated with increased black carbon content in airway macrophages of former smokers with COPD. AB - INTRODUCTION: Exposure to fine particulate matter (PM2.5) is associated with worse morbidity in individuals with COPD. Inhaled PM is phagocytosed by airway macrophages (AM), and black carbon measured in AM may serve as a biomarker of air pollution exposure. As there is little data on how indoor PM exposure may influence AM black carbon content in those with respiratory disease, we investigated the association of indoor PM2.5 concentration to AM black carbon content in adults with COPD. METHODS: Former smokers (>10 pack-years smoking history, quit date >1 year prior to enrollment) older than 40 years of age with moderate-severe COPD were eligible. Indoor air PM2.5 concentrations were measured over 5-7 days at baseline, 3 month, and 6 month intervals. Sputum induction was performed during clinic visits concordant with home monitoring. A total of 50 macrophages per sputum specimen were photographed and quantified using appropriate software by trained staff blinded to PM concentrations. Longitudinal analyses using generalized estimating equations were used to assess the relationship between indoor PM exposure and AM black carbon content. RESULTS: Participants (n=20) were older (mean (SD) age 67 (4) years), predominantly Caucasian (85%) and male (70%), with an average smoking history of 52 pack-years and mean (SD) quit date of 13 (9) years prior to enrollment. The majority of daily time was reported to be spent indoors (>23h). Mean indoor PM2.5 concentration was 12.8 (13.5)ug/m(3). The mean area of black carbon quantified in airway macrophages was 1.2 (0.7)um(2). In multivariate cross-sectional and longitudinal analyses, each 10ug/m(3) increase in indoor PM2.5 was significantly associated with a 0.26um(2) and 0.19um(2) increase in airway macrophage black carbon total area, respectively (p<0.05). CONCLUSION: Higher indoor PM2.5 concentration is associated with an increase in black carbon content of AM in individuals with COPD. These data support the potential for AM black carbon content to be a useful non-invasive biomarker of exposure to indoor PM. PMID- 27372064 TI - Mercury, hydroquinone and clobetasol propionate in skin lightening products in West Africa and Canada. AB - Skin lightening products are types of cosmetics (creams, gels, lotions and soaps) applied voluntarily on skin. Several of these products contain a variety of active ingredients that are highly toxic. Among those toxic agents, the present study focuses on mercury, hydroquinone, and clobetasol propionate. Out of the 93 lightening soaps and 98 creams purchased in large city markets in sub-Saharan West Africa and in small ethnic shops in Canada, 68-84% of all creams and 7.5-65% of all soaps exceeded regulatory guidelines for at least one active ingredient when considering different regulations. Mercury was found in high concentrations mainly in soaps, while hydroquinone and clobetasol propionate concentrations exceeded US FDA standards in some creams for all countries included in our study. Concentrations of the three compounds declared on labels of soaps and creams usually did not correspond to concentrations actually measured, particularly for mercury and hydroquinone. Overall, our results indicate that most studied skin lightening products are potentially toxic and that product labels are frequently inaccurate with respect to the presence of toxic agents. PMID- 27372065 TI - Dietary exposure and human risk assessment of phthalate esters based on total diet study in Cambodia. AB - Phthalate esters are used in a wide variety of consumer products, and human exposure to this class of compounds is widespread. Nevertheless, studies on dietary exposure of human to phthalates are limited. In this study, to assess the daily intakes of phthalate esters and the possible adverse health impacts, different food samples were collected from three areas of Cambodia, one of the poorest countries in the world. The ?phthalate ester concentrations in Kampong Cham, Kratie and Kandal provinces ranged from 0.05 to 2.34 (median 0.88) MUgg( 1), 0.19-1.65 (median 0.86) MUgg(-1) and 0.24-3.05 (median 0.59) MUgg(-1) wet weight (ww), respectively. Di-2-Ethylhexyl phthalate (DEHP) and diisobutyl phthalate (DiBP) were the predominant compounds among all foodstuffs. The estimated daily intake (EDI) of phthalate esters for the general population in Kampong Cham, Kratie and Kandal was 34.3, 35.6 and 35.8MUgkg(-1) bw d(-1), respectively. The dietary daily intake of DEHP, benzylbutyl phthalate (BBP) and di-n-butyl phthalate (DBP) in Kampong Cham, Kratie and Kandal were below the tolerable daily intakes (TDI) imposed by the European Food Safety Authority (EFSA) and reference doses (RfD) imposed by The United States Environmental Protection Agency (USEPA). Rice contributed the greatest quantity of DEHP to the daily intake in Cambodia so may deserve further exploration. To our knowledge, this is the first study to investigate the occurrence and the daily intakes of phthalate esters in Cambodia. PMID- 27372069 TI - Tumor-infiltrating lymphocytes (TILs) are a powerful prognostic marker in patients with triple-negative breast cancer enrolled in the IBCSG phase III randomized clinical trial 22-00. AB - The purpose of this study was to assess the prognostic and predictive value of tumor-infiltrating lymphocytes (TILs) in the triple-negative breast cancer (TNBC) cohort of the phase III IBCSG trial 22-00, comparing low-dose oral 'metronomic' cyclophosphamide-methotrexate maintenance chemotherapy (CM-maintenance) to no-CM maintenance in early breast cancer. TILs were evaluated in full-face hematoxylin and-eosin-stained sections of tumor samples confirmed centrally as TNBC (< 1 % of ER and PgR immunoreactivity and absence of HER2 overexpression or amplification). Mononuclear cells were evaluated in the stromal area within the borders of the invasive tumor. The primary endpoint was breast cancer-free interval (BCFI). Cox proportional hazards regression model assessed the association of BCFI and secondary endpoints with TILs score. In the 647 tumor samples, the median percentage of TILs was 18 % (IQR = 8-40 %), with 18 % having TILs >= 50 % (lymphocyte-predominant breast cancer, LPBC). At a median follow-up of 6.9 years, TILs were associated with better prognosis. For every 10 % increase of TILs, BCFI risk reduction was 13 % (HR 0.87, 95 % CI 0.79-0.95,P = 0.003). DFS, DRFI, and OS risk reductions were 11 % (P = 0.005), 16 % (P = 0.003), and 17 % (P < 0.001), respectively. Multivariable analysis confirmed the independent prognostic value of TILs. No significant TILs-by-treatment interaction was observed (P = 0.39) for associations of TILs with BCFI, although patients with LPBC receiving CM maintenance had a greater breast cancer risk reduction (HR 0.64,95 % CI 0.23 1.78) than those with non-LPBC (TILs < 50 %) (HR 0.96, 95 % CI 0.67-1.40). TILs score is a potent prognostic factor in patients with TNBC. Low-dose chemotherapy confers a greater (not statistically significant) clinical benefit in patients with LPBC. PMID- 27372071 TI - Stress Detection Using Low Cost Heart Rate Sensors. AB - The automated detection of stress is a central problem for ambient assisted living solutions. The paper presents the concepts and results of two studies targeted at stress detection with a low cost heart rate sensor, a chest belt. In the device validation study ( n = 5), we compared heart rate data and other features from the belt to those measured by a gold standard device to assess the reliability of the sensor. With simple synchronization and data cleaning algorithm, we were able to select highly (>97%) correlated, low average error (2.2%) data segments of considerable length from the chest data for further processing. The protocol for the clinical study ( n = 46) included a relax phase followed by a phase with provoked mental stress, 10 minutes each. We developed a simple method for the detection of the stress using only three time-domain features of the heart rate signal. The method produced accuracy of 74.6%, sensitivity of 75.0%, and specificity of 74.2%, which is impressive compared to the performance of two state-of-the-art methods run on the same data. Since the proposed method uses only time-domain features, it can be efficiently implemented on mobile devices. PMID- 27372070 TI - Recurrent and pathological gene fusions in breast cancer: current advances in genomic discovery and clinical implications. AB - Gene fusions have long been considered principally as the oncogenic events of hematologic malignancies, but have recently gained wide attention in solid tumors due to several milestone discoveries and the advancement of deep sequencing technologies. With the progress in deep sequencing studies of breast cancer transcriptomes and genomes, the discovery of recurrent and pathological gene fusions in breast cancer is on the focus. Recently, driven by new deep sequencing studies, several recurrent or pathological gene fusions have been identified in breast cancer, including ESR1-CCDC170, SEC16A-NOTCH1, SEC22B-NOTCH2, and ESR1 YAP1 etc. More important, most of these gene fusions are preferentially identified in the more aggressive breast cancers, such as luminal B, basal-like, or endocrine-resistant breast cancer, suggesting recurrent gene fusions as additional key driver events in these tumors other than the known drivers such as the estrogen receptor. In this paper, we have comprehensively summarized the newly identified recurrent or pathological gene fusion events in breast cancer, reviewed the contributions of new genomic and deep sequencing technologies to new fusion discovery and the integrative bioinformatics tools to analyze these data, highlighted the biological relevance and clinical implications of these fusion discoveries, and discussed future directions of gene fusion research in breast cancer. PMID- 27372072 TI - Problem solving, impulse control and planning in patients with early- and late stage Huntington's disease. AB - Sub-domains of executive functions, including problems with planning, accuracy, impulsivity, and inhibition, are core features of Huntington's disease. It is known that the decline of cognitive function in Huntington's disease is related to the anatomical progression of pathology in the basal ganglia. However, it remains to be determined whether the severity of executive dysfunction depends on the stage of the disease. To examine the severity of sub-domains of executive dysfunction in early- and late-stage Huntington's disease, we studied performance in the Tower of London task of two groups of Huntington's disease patients (Group 1: early, n = 23, and Group 2: late stage, n = 29), as well as a third group of age, education, and IQ matched healthy controls (n = 34). During the task, we measured the total number of problems solved, total planning time, and total number of breaks taken. One aspect of executive function indexed by the number of solved problems seems to progress in the course of the disease. Late-stage Huntington's disease patients scored significantly worse than early-stage patients and controls, and early-stage patients scored significantly worse than controls on this measure of accuracy. In contrast, late- and early-stage HD patients did not differ in terms of planning time and number of breaks. Early- and late-stage HD pathology has a different impact on executive sub-domains. While accuracy differs between early- and late-stage HD patients, other domains like planning time and number of breaks do not. Striatal degeneration, which is a characteristic feature of the disease, might not affect all aspects of executive function in HD. PMID- 27372073 TI - Association of Lactase Persistence Genotypes with High Intake of Dairy Saturated Fat and High Prevalence of Lactase Non-Persistence among the Mexican Population. AB - BACKGROUND/AIM: Lactase (LCT) -13910 C>T and -22018 G>A polymorphisms associated with the lactase non-persistence (LNP)/persistence (LP) phenotypes vary globally. LP has been associated with obesity in Europeans. However, it has not been genetically evaluated in Mexico, a country with admixed population, recent introduction of dairy, and a high prevalence of obesity. Thus, we aimed to determine the distribution of the LCT polymorphisms and their association with the nutritional profile of West Mexico's populations. METHODS: Genotyping of 1,196 individuals (natives and mestizos) was carried out by a Taqman allelic discrimination assay. Descriptive statistics and interpopulation analyzes were performed by SPSS, Arlequin, and Structure software. Demographic, anthropometric, biochemical and dietary data were analyzed in 212 mestizos. RESULTS: LNP genotypes mainly prevailed (CC 68.7% and GG 68.2%); both predominated in native Huicholes and Nahuas (>97.7%). Among the mestizos, the LP genotypes were associated with a higher intake of saturated fat (9.9 +/- 3.9% vs. 8.5 +/- 4.0%, p = 0.018; OR = 2.55, 95% CI 1.29-5.03, p = 0.006) and a daily/more frequent consumption of dairy (88.8 vs. 78.0%; p = 0.049) than LNP genotypes. CONCLUSION: The LNP trait was predominant in Mexicans with a major Amerindian ancestry. A daily consumption of dairy was associated with a higher intake of saturated fat in LP individuals. PMID- 27372074 TI - Aortic valve aneurysm associated with infective endocarditis: case report and review of literature. AB - Although there are several mitral valve aneurysm reports, studies on aortic valve aneurysm are extremely rare. This paper describes an uncommon case of a large saccular aortic valve aneurysm associated with infective endocarditis. A 37-year old man was hospitalized in our hospital with fever and dyspnea. Echocardiography found severe aortic regurgitation and aortic valve aneurysm of the non-coronary cusp going in and out of the left ventricular chamber. Blood cultures grew Streptococcus viridance. Therefore, the patient underwent aortic valve replacement. During the operation, we observed a 30 * 20 mm ruptured aneurysm that arose from the non-coronary cusp. The aortic valve containing the aneurysm was resected and replaced with a mechanical heart valve. Histopathological examination of the aortic valve aneurysm showed active inflammatory changes. Infective endocarditis was considered to be the cause of this aortic valve aneurysm. PMID- 27372075 TI - Multiplex assay for subtyping avian influenza A viruses by cDNA hybridization and adapter-mediated amplification. AB - Multiple subtypes of influenza A viruses circulating in animals must be closely monitored to understand their risk to humans and animal populations. Many molecular-based subtyping methods require constant monitoring of viral genomes for primer and/or probe mismatches and are prone to primer-primer interactions. This report presents a new approach that involves target enrichment through cDNA hybridization followed by adapter-mediated amplification for subtyping influenza virus (AmASIV). As a proof of concept, the AmASIV assay was multiplexed to specifically detect and differentiate influenza A virus subtypes (H5, N5, N7, and N9) in a single reaction without cross-recognition of nontarget subtypes or influenza B virus. The limit of detection (LOD) of AmASIV, as measured by 50 % egg-infective dose per reaction (EID50/reaction), was comparable to that of singleplex TaqMan(r) qPCR assays with LODs of 10(-0.6) (H5), 10(2) (N5), 10(-0.3) (N7), and 10(-0.5) (N9) EID50/reaction. The AmASIV will strengthen animal influenza virus surveillance and laboratory capacity to improve prevention and control of influenza. PMID- 27372076 TI - Characterization of novel DeoR-family member from the Streptomyces ahygroscopicus strain CK-15 that acts as a repressor of morphological development. AB - Wuyiencin is produced by Streptomyces ahygroscopicus var. wuyiensis, which has been widely used in China as an industrially produced biopesticide to control various fungal diseases. Although its mechanism of action, breeding, and fermentation had been extensively characterized, less is known about the regulatory functions that affect its biosynthesis or morphological development. The wysR3 gene of S. ahygroscopicus strain CK-15, a novel member of the DeoR family of regulatory genes, was assessed to determine its function by gene knockdown. Herein, we demonstrate for the first time that DeoR family proteins derived from the same source are likely to be a single branch in a phylogenetic tree and show that wysR3 acts as a repressor for its morphological development without effecting wuyiencin production. We found that the DeltawysR3 strain can grow quickly to reach a plateau stage of maximum biomass at 60 h, which is ~12 h faster than the wild-type strain. In the industrial fermentation production process, the DeltawysR3 strain can reduce consumption and save both time and money. PMID- 27372077 TI - Association of markers of endothelial dysregulation Ang1 and Ang2 with acute kidney injury in critically ill patients. AB - BACKGROUND: The role of endothelial dysregulation with acute kidney injury (AKI) in critically ill patients is unclear. METHODS: We retrospectively assessed the associations of AKI with biomarkers of endothelial function and inflammation among 948 subjects admitted to the intensive care unit (ICU) at Harborview Medical Center (Seattle, WA, USA). From plasma obtained within 24 h of enrollment, we measured angiopoietin (Ang)-1 and Ang-2 alongside biomarkers of inflammation, including interleukin (IL)-6, IL-17 and granulocyte colony stimulating factor. We tested for associations between standardized concentrations of biomarkers and AKI, defined by serum creatinine, from ICU admission to up to 7 days later. RESULTS: All biomarkers of inflammation and endothelial dysfunction were associated with AKI. After adjustment for demographics, comorbidities, and IL-6 concentration, every standard deviation of Ang-1 concentration was associated with a 19 % lower risk of AKI (relative risk (RR) = 0.85, 95 % confidence interval (CI) 0.77-0.93, p < 0.001). Conversely, higher Ang-2 concentration was associated with higher risk of AKI (RR per standard deviation = 1.17, 95 % CI 1.13-1.22, p < 0.001). CONCLUSIONS: In critically ill patients, plasma concentration of the endothelial growth factors Ang-1 and Ang-2 are associated with AKI, independently of inflammation. PMID- 27372078 TI - Influenza and pneumococcal vaccination in patients with rheumatoid arthritis in comparison with age- and sex-matched controls: results of a claims data analysis. AB - The aim of this study was to assess the vaccination status for influenza and pneumonia and the prevalence of hospitalised pneumonia in rheumatoid arthritis (RA) patients and population controls in Germany. Members of a large statutory health insurance fund in Germany who were continuously insured between 2009 and 2013 and had a diagnosis of RA in 2013 were age and sex matched 1:5 to members without RA. Pneumococcal and influenza vaccinations were evaluated with regard to age, sex and region of residence. Logistic regression models were used to determine predictors for influenza vaccination in RA patients. Prevalences of pneumonia that required hospitalisation were compared to regional vaccination rates. The data of 111,482 RA patients and 557,410 matched controls were available for analysis. Compared to controls, RA patients were vaccinated more frequently against influenza (40.8 vs. 32.2 %) and pneumonia (15.0 vs. 10.0 %). Vaccination rates increased with older age and differed between the federal states (highest in East Germany, lowest in South Germany). The region of residence, comorbidities, rheumatologic care and biologic treatment was associated with a higher probability of an influenza vaccination. Prevalences of pneumonia that required hospitalisation were 2-3 times higher in patients compared to controls and tended to be higher in regions with low vaccination rates. The increased pneumonia prevalence in RA patients confirms their status as a risk group. RA patients are vaccinated more frequently than controls, but vaccination rates are still low. The lower pneumonia prevalence in East Germany indicates that vaccination may help to reduce pneumonia in RA. PMID- 27372081 TI - Practical Application of Elastography in the Diagnosis of Thyroid Nodules in Children and Adolescents. AB - BACKGROUND: Ultrasound elastography is a noninvasive method of imaging based on the estimation of the mechanical properties of tissue. Data in adults indicate that decreased flexibility in comparison to the surrounding healthy tissue is characteristic of malignancy (in most thyroid carcinomas, except for follicular thyroid carcinoma). The purpose of our study was to assess the deformation of thyroid nodules and to evaluate the usefulness of elastography in predicting malignant thyroid nodules in adolescent patients. METHODS: We examined 47 children with 62 thyroid nodules. All patients underwent elastography and fine needle aspiration cytology (FNAC). RESULTS: Thirty-seven girls (79%) and 10 boys (21%) were included in the study. A strain ratio <2 was observed in 17 nodules (27% of the study group), a strain ratio between 2 and 4.9 in 34 nodules (55%) and a strain ratio >5 in 11 nodules (18%). According to cytological examination, 3 nodules (4.8% of the study group) were malignant. Two of them were hard (strain ratio >=5), and 1 nodule had a strain ratio of 2. CONCLUSIONS: Our results suggest that elastography can be complementary to conventional ultrasonography and useful while making a decision about FNAC. At the same time, it should not replace the cytological assessment of thyroid nodules in children and adolescents. PMID- 27372080 TI - Short-term outcomes of laparoscopic surgery for Crohn's disease patients treated with anti-tumor necrosis factor alpha agents. AB - PURPOSE: The impact of anti-tumor necrosis factor alpha (TNFalpha) treatment for Crohn's disease (CD) on surgical outcomes is still controversial. The aim of this study was to assess the feasibility of laparoscopic surgery for CD patients treated preoperatively with anti-TNFalpha agents. METHODS: We investigated, retrospectively, the clinical features and surgical outcomes of 35 consecutive CD patients who underwent laparoscopic surgery after receiving scheduled anti TNFalpha treatment preoperatively. We compared the surgical outcomes of an "early surgery group", comprised of patients who underwent surgery less than 3 years after the initiation of anti-TNFalpha treatment, with those of a "late surgery group", comprised of patients who underwent surgery more than 3 years after the initiation of anti-TNFalpha treatment. RESULTS: The mean operating time and blood loss were 203 min and 259 mL, respectively. The rates of conversion to open surgery and postoperative complications were 8.6 and 11.4 %, respectively. Operating time and blood loss were correlated with the interval between the initiation of anti-TNFalpha agent treatment and the time of surgery. The proportion of patients with acquired resistance to anti-TNFalpha agents and the rate of conversion to open surgery were higher and operating times were longer in the late surgery group than in the early surgery group. CONCLUSION: Laparoscopic surgery can be performed safely for CD patients treated preoperatively with anti TNFalpha agents, although operating times may be longer and estimated blood loss (EBL) greater for those who have been on prolonged anti-TNFalpha treatment. PMID- 27372079 TI - Centre-related variability in hospital admissions of patients with spondyloarthritis. AB - The aim of this study was to explore the variability in hospital admissions of patients with spondyloarthritis (SpA) in Spain, and the centre factors that may influence that variability. Descriptive cross-sectional study, part of the emAR II study, performed in Spain (2009-2010). Health records of patients with a diagnosis of SpA and at least one visit to the rheumatology units within the previous 2 years were reviewed. Variables related to hospital admissions, to the SpA, and to the patient and centre were collected. A multilevel logistic regression analysis of random intercept with non-random slopes was performed to assess variability between centres. From 45 centres, 1168 patients' health records were reviewed. Main SpA forms were ankylosing spondylitis (55.2 %) and psoriatic arthritis (22.2 %). A total of 248 admissions were registered for 196 patients (19.2 %, n = 1020). An adjusted variability of 17.6 % in hospitalizations between centres was noted. The following hospital-related factors showed a significant association with admissions: the total number of admissions of the centre, the existence of electronic admission, and the availability of ultrasound in rheumatology. However, these factors only explained 42.9 % of the inter-centre variability. The risk of a patient with SpA of being admitted could double (median OR 2.09), depending on the hospital where the patient was being managed. Hospital admissions of patients with SpA varied between hospitals due to centre characteristics. Further studies are needed to ascertain which specific factors may be causing the variation, as studied variables explained less than half of the variability. PMID- 27372084 TI - [Not Available]. PMID- 27372083 TI - [Not Available]. PMID- 27372082 TI - In vitro digestibility and proteases inhibitory effect of several feedstuffs for Parachromis dovii juveniles and P. dovii hybrid larvae. AB - Parachromis dovii, a native cichlid from Costa Rica, is highly appreciated for its size and flesh quality. Further, P. dovii easily accept inert feed from the beginning of exogenous feeding; however, its growth is low compared to live food. For this reason, evaluation of several feedstuffs using two in vitro techniques was done. The quantification of the in vitro inhibitory effect of seven plant ingredients on the alkaline protease activity was done using enzymatic extracts from larvae samples of 6, 15, 22 and 30 days after hatching (DAH). The in vitro alkaline digestibility assays were run for six protein sources (from animal and plant origin) using the enzymatic extract from larvae 30 DAH. Independent of fish age, all plant feedstuffs reduced alkaline digestive proteases activity; however, the wheat flour (14.1 % at 6 DAH, 33.4 % at 15 DAH) and broken rice meal (51.6 % at 22 DAH) showed the lowest inhibition percentage of alkaline digestive activity, whereas the highest inhibition percentage was found with soybean and palm kernel meals (92.5 % at 30 DAH and 87.4 %, respectively) (P < 0.05). The alkaline proteases inhibition percentage of feedstuffs varied during larvae ontogeny. From six protein dietary sources tested, tankage and fish meal presented the highest in vitro digestibility values, 113.9 and 74.9 %, respectively. Contrary, the lowest digestibility was found for blood and soybean meals (38.07 and 19.82 %, respectively). PMID- 27372085 TI - [Not Available]. PMID- 27372086 TI - [Not Available]. PMID- 27372087 TI - [Not Available]. PMID- 27372088 TI - [Not Available]. PMID- 27372089 TI - [Not Available]. PMID- 27372090 TI - [Not Available]. PMID- 27372091 TI - [Not Available]. PMID- 27372092 TI - [Not Available]. PMID- 27372093 TI - [Not Available]. PMID- 27372094 TI - [Not Available]. PMID- 27372095 TI - [Not Available]. PMID- 27372096 TI - [Not Available]. PMID- 27372097 TI - Pleurodesis with Thulium Cyber Laser versus talc poudrage: a comparative experimental study. AB - Sclerosing fluids to achieve pleurodesis could be hardly replaced for bed-side procedures, but other devices may be successfully applied during thoracoscopy. Thulium Cyber Laser was experimented for this purpose and compared to talc poudrage. Twenty pigs underwent operative videothoracoscopy (VATS). Ten models were subjected to double-port VATS and parietal pleura photoevaporation using Thulium Cyber LaserTM (TCL) 150 W 2010 nm on the posterior third of three ribs; the pleural surface was homogeneously treated inside the target perimeter. The remaining ten pigs underwent uniportal thoracoscopy; talc poudrage was performed using the current clinical practice dosage (1 g/18 kg) with accurate talc powder spread over the whole pleural surface. All models were followed up for 60 days. Pleurodesis firmness was graded on a three-tier scale (none-moderate-firm) and site-matching topographical expectancy was evaluated. TCL produced pleurodesis in all models: 7/10 were firm and 3/10 moderate. Talc poudrage pleurodesis was firm in 4/10 and moderate in 6/10. Pleural adhesions were found exclusively in the treated area after laser treatment, while talc created a wide spectrum of effects, most commonly anarchic jagged adhesions obliterating less than 50 % of the pleural cavity (7/10), mostly declivous. The pathologist found more aggressive inflammation (sometimes severe) in the talc group. Expected localized pleurodesis was always registered in laser group (10/10), while talc poudrage was found poorly effective if consistent pleurodesis is expected in an apico-dorsal position (2/10). Laser pleurodesis appears more homogeneous, qualitatively not inferior, and topographically more predictable than talc pleurodesis. Parietal photoevaporation seems effective and the localized pleurodesis is reproducible. PMID- 27372100 TI - Thermal destruction of wastes containing polychlorinated naphthalenes in an industrial waste incinerator. AB - A series of verification tests were carried out in order to confirm that polychlorinated naphthalenes (PCNs) contained in synthetic rubber products (Neoprene FB products) and aerosol adhesives, which were accidentally imported into Japan, could be thermally destroyed using an industrial waste incinerator. In the verification tests, Neoprene FB products containing PCNs at a concentration of 2800 mg/kg were added to industrial wastes at a ratio of 600 mg Neoprene FB product/kg-waste, and then incinerated at an average temperature of 985 degrees C. Total PCN concentrations were 14 ng/m3N in stack gas, 5.7 ng/g in bottom ash, 0.98 ng/g in boiler dust, and 1.2 ng/g in fly ash. Destruction efficiency (DE) and destruction removal efficiency (DRE) of congener No. 38/40, which is considered an input marker congener, were 99.9974 and 99.9995 %, respectively. The following dioxin concentrations were found: 0.11 ng-TEQ/m3N for the stack gas, 0.096 ng-TEQ/g for the bottom ash, 0.010 ng-TEQ/g for the boiler dust, and 0.072 ng-TEQ/g for the fly ash. Since the PCN levels in the PCN destruction test were even at slightly lower concentrations than in the baseline test without PCN addition, the detected PCNs are to a large degree unintentionally produced PCNs and does not mainly stem from input material. Also, the dioxin levels did not change. From these results, we confirmed that PCNs contained in Neoprene FB products and aerosol adhesives could be destroyed to a high degree by high-temperature incineration. Therefore, all recalled Neoprene FB products and aerosol adhesives containing PCNs were successfully treated under the same conditions as the verification tests. PMID- 27372099 TI - Clinical Phenotype of Adult Fragile X Gray Zone Allele Carriers: a Case Series. AB - Considerable research has focused on patients with trinucleotide (CGG) repeat expansions in the fragile X mental retardation 1 (FMR1) gene that fall within either the full mutation (>200 repeats) or premutation range (55-200 repeats). Recent interest in individuals with gray zone expansions (41-54 CGG repeats) has grown due to reported phenotypes that are similar to those observed in premutation carriers, including neurological, molecular, and cognitive signs. The purpose of this manuscript is to describe a series of adults with FMR1 alleles in the gray zone presenting with movement disorders or memory loss. Gray zone carriers ascertained in large FMR1 screening studies were identified and their clinical phenotypes studied. Thirty-one gray zone allele carriers were included, with mean age of symptom onset of 53 years in patients with movement disorders and 57 years in those with memory loss. Four patients were chosen for illustrative case reports and had the following diagnoses: early-onset Parkinson disease (PD), atypical parkinsonism, dementia, and atypical essential tremor. Some gray zone carriers presenting with parkinsonism had typical features, including bradykinesia, rigidity, and a positive response to dopaminergic medication. These patients had a higher prevalence of peripheral neuropathy and psychiatric complaints than would be expected. The patients seen in memory clinics had standard presentations of cognitive impairment with no apparent differences. Further studies are necessary to determine the associations between FMR1 expansions in the gray zone and various phenotypes of neurological dysfunction. PMID- 27372098 TI - Interhemispheric Connectivity Characterizes Cortical Reorganization in Motor Related Networks After Cerebellar Lesions. AB - Although cerebellar-cortical interactions have been studied extensively in animal models and humans using modern neuroimaging techniques, the effects of cerebellar stroke and focal lesions on cerebral cortical processing remain unknown. In the present study, we analyzed the large-scale functional connectivity at the cortical level by combining high-density electroencephalography (EEG) and source imaging techniques to evaluate and quantify the compensatory reorganization of brain networks after cerebellar damage. The experimental protocol comprised a repetitive finger extension task by 10 patients with unilateral focal cerebellar lesions and 10 matched healthy controls. A graph theoretical approach was used to investigate the functional reorganization of cortical networks. Our patients, compared with controls, exhibited significant differences at global and local topological level of their brain networks. An abnormal rise in small-world network efficiency was observed in the gamma band (30-40 Hz) during execution of the task, paralleled by increased long-range connectivity between cortical hemispheres. Our findings show that a pervasive reorganization of the brain network is associated with cerebellar focal damage and support the idea that the cerebellum boosts or refines cortical functions. Clinically, these results suggest that cortical changes after cerebellar damage are achieved through an increase in the interactions between remote cortical areas and that rehabilitation should aim to reshape functional activation patterns. Future studies should determine whether these hypotheses are limited to motor tasks or if they also apply to cerebro-cerebellar dysfunction in general. PMID- 27372102 TI - [Not Available]. PMID- 27372103 TI - [Not Available]. PMID- 27372101 TI - Phthalate pollution in an Amazonian rainforest. AB - Phthalates are ubiquitous contaminants and endocrine-disrupting chemicals that can become trapped in the cuticles of insects, including ants which were recognized as good bioindicators for such pollution. Because phthalates have been noted in developed countries and because they also have been found in the Arctic, a region isolated from direct anthropogenic influence, we hypothesized that they are widespread. So, we looked for their presence on the cuticle of ants gathered from isolated areas of the Amazonian rainforest and along an anthropogenic gradient of pollution (rainforest vs. road sides vs. cities in French Guiana). Phthalate pollution (mainly di(2-ethylhexyl) phthalate (DEHP)) was higher on ants gathered in cities and along road sides than on those collected in the pristine rainforest, indicating that it follows a human-mediated gradient of disturbance related to the use of plastics and many other products that contain phthalates in urban zones. Their presence varied with the ant species; the cuticle of Solenopsis saevissima traps higher amount of phthalates than that of compared species. However, the presence of phthalates in isolated areas of pristine rainforests suggests that they are associated both with atmospheric particles and in gaseous form and are transported over long distances by wind, resulting in a worldwide diffusion. These findings suggest that there is no such thing as a "pristine" zone. PMID- 27372105 TI - [Not Available]. PMID- 27372104 TI - [Not Available]. PMID- 27372106 TI - Chemoprevention of Keratinocyte Carcinomas: An Updated Review. AB - A well-established link between ultraviolet exposure and the carcinogenesis of keratinocyte carcinomas exists. Despite increased sun protection efforts, skin cancer remains the most common cancer in the USA. Numerous studies on the topic of chemoprevention investigate alternative topical, oral, and injectable agents to reduce skin cancer incidence in those at risk. Such agents include sunscreen, numerous vitamins and minerals, difluoromethylornithine, non-steroidal anti inflammatory drugs, various peptides, field therapy, statins, and polyphenols. In this focused review, we discuss the risks and benefits of chemoprotective agents reported in clinical studies conducted in humans. We report several agents that may reduce skin cancer incidence in those at risk. PMID- 27372107 TI - Striking Effects of Storage Buffers on Apparent Half-Lives of the Activity of Pseudomonas aeruginosa Arylsulfatase. AB - To obtain the label enzyme for enzyme-linked-immunoabsorbent-assay of two components each time in one well with conventional microplate readers, molecular engineering of Pseudomonas aeruginosa arylsulfatase (PAAS) is needed. To compare thermostability of PAAS/mutants of limited purity, effects of buffers on the half activity time (t 0.5) at 37 degrees C were tested. At pH 7.4, PAAS showed non exponential decreases of activity, with the apparent t 0.5 of ~6.0 days in 50 mM HEPES, but ~42 days in 10 mM sodium borate with >85 % activity after 15 days; protein concentrations in both buffers decreased at slower rates after there were significant decreases of activities. Additionally, the apparent t 0.5 of PAAS was ~14 days in 50 mM Tris-HCl, and ~21 days in 10 mM sodium phosphate. By sodium dodecyl-polyacrylamide gel electrophoresis, the purified PAAS gave single polypeptide; after storage for 14 days at 37 degrees C, there were many soluble and insoluble fragmented polypeptides in the HEPES buffer, but just one principal insoluble while negligible soluble fragmented polypeptides in the borate buffer. Of tested mutants in the neutral borate buffer, rates for activity decreases and polypeptide degradation were slower than in the HEPES buffer. Hence, dilute neutral borate buffers were favorable for examining thermostability of PAAS/mutants. PMID- 27372109 TI - Omarigliptin for the treatment of type 2 diabetes. AB - Omarigliptin is a new once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor developed for the treatment of type 2 diabetes. It is indicated to have favorable effects on glycosylated hemoglobin (HbA1c), fasting and postmeal plasma glucose. It potently but reversibly inhibits DPP-4 enzyme, which prolongs the circulating half-life of glucagon-like peptide-1 that increases insulin secretion in a glucose-dependent manner. Benefiting from glucose-dependent insulin secretion, omarigliptin is associated with low risk of hypoglycemia. In contrast to the once daily dipeptidyl peptidase-4 inhibitors (e.g., alogliptin, linagliptin, sitagliptin), once-weekly omarigliptin can improve patients' adherence and thus achieve optimal therapeutic efficacy. Herein, I review the pharmacological and clinical profile of omarigliptin for the treatment of type 2 diabetes based on the available clinical data. PMID- 27372110 TI - An observational study of the impact of the 2014 XX Commonwealth Games on the sexual and reproductive health services in Glasgow, Scotland. AB - Background: Large sporting events have raised concerns about the effect on the sexual and reproductive health (SRH) of visiting and resident populations to the host city and increased demand on SRH services. However, there is little evidence to support these concerns. The aim of this study is to investigate if the 2014 XX Commonwealth Games had an effect on the service demands of a Glasgow city-wide integrated SRH service. Methods: Electronic patient records, city-wide pharmacy data and case note review was used to assess aspects of SRH; this included overall attendance at integrated services, clinic and community emergency contraception prescriptions, victims of sexual assault, acute sexually transmissible infections (STIs), post exposure prophylaxis after sexual exposure (PEPSE) prescriptions, condom distribution and termination of pregnancy. Results: There was a significant decrease in core sexual health attendances, total acute STIs and emergency hormonal contraception prescriptions. There was no change in PEPSE prescriptions or the number of reported sexual assaults throughout the city. Conclusions: This study found no evidence that the 2014 XX Commonwealth Games placed any increased demand on the local SRH services, and showed no increase in STIs, emergency hormonal contraception prescriptions or sexual assaults. These findings will help service planning in host cities hosting future large sporting events. PMID- 27372112 TI - Hepatorenal syndrome. PMID- 27372108 TI - Sleep Duration and Obesity in Adults: What Are the Connections? AB - Collectively, cross-sectional and longitudinal studies on self-reported sleep duration and obesity do not show a clear pattern of association with some showing a negative linear relationship, some showing a U-shaped relationship, and some showing no relationship. Associations between sleep duration and obesity seem stronger in younger adults. Cross-sectional studies using objectively measured sleep duration (actigraphy or polysomnography (PSG)) also show this mixed pattern whereas all longitudinal studies to date using actigraphy or PSG have failed to show a relationship with obesity/weight gain. It is still too early and a too easy solution to suggest that changing the sleep duration will cure the obesity epidemic. Given novel results on emotional stress and poor sleep as mediating factors in the relationship between sleep duration and obesity, detection and management of these should become the target of future clinical efforts as well as future research. PMID- 27372113 TI - Variation in assimilable organic carbon formation during chlorination of Microcystis aeruginosa extracellular organic matter solutions. AB - This study investigated the chlorination of Microcystis aeruginosa extracellular organic matter (EOM) solutions under different conditions, to determine how the metabolites produced by these organisms affect water safety and the formation of assimilable organic carbon (AOC). The effects of chlorine dosages, coagulant dosage, reaction time and temperature on the formation of AOC were investigated during the disinfection of M.aeruginosa metabolite solutions. The concentration of AOC followed a decreasing and then increasing pattern with increasing temperature and reaction time. The concentration of AOC decreased and then increased with increasing chlorination dosage, followed by a slight decrease at the highest level of chlorination. However, the concentration of AOC decreased continuously with increasing coagulant dosage. The formation of AOC can be suppressed under appropriate conditions. In this study, chlorination at 4mg/L, combined with a coagulant dose of 40mg/L at 20 degrees C over a reaction time of 12hr, produced the minimum AOC. PMID- 27372114 TI - Fabrication and performance of PET mesh enhanced cellulose acetate membranes for forward osmosis. AB - Polyethylene terephthalate mesh (PET) enhanced cellulose acetate membranes were fabricated via a phase inversion process. The membrane fabrication parameters that may affect the membrane performance were systematically evaluated including the concentration and temperature of the casting polymer solution and the temperature and time of the evaporation, coagulation and annealing processes. The water permeability and reverse salt flux were measured in forward osmosis (FO) mode for determination of the optimal membrane fabrication conditions. The optimal FO membrane shows a typical asymmetric sandwich structure with a mean thickness of about 148.2MUm. The performance of the optimal FO membrane was tested using 0.2mol/L NaCl as the feed solution and 1.5mol/L glucose as the draw solution. The membrane displayed a water flux of 3.47L/(m(2).hr) and salt rejection of 95.48% in FO mode. While in pressure retarded osmosis (PRO) mode, the water flux was 4.74L/(m(2).hr) and salt rejection 96.03%. The high ratio of water flux in FO mode to that in PRO mode indicates that the fabricated membrane has a lower degree of internal concentration polarization than comparable membranes. PMID- 27372115 TI - Effects of Al(3+) doping on the structure and properties of goethite and its adsorption behavior towards phosphate. AB - Al substitution in goethite is common in soils, and has strong influence on the structure and physicochemical properties of goethite. In this research, a series of Al-doped goethites were synthesized, and characterized by powder X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR) and extended X-ray absorption fine structure (EXAFS) spectroscopy. The adsorption behavior of these samples towards PO4(3-) was also investigated. Characterization results demonstrated that increasing Al content in goethite led to a reduction in crystallinity, increase in specific surface area (SSA), and morphology change from needle-like to granular. Rietveld structure refinement revealed that the lattice parameter a remained almost constant and b slightly decreased, but c was significantly reduced, and the calculated crystal density increased. EXAFS analysis demonstrated that the Fe(Al)-O distance in the structure of the doped goethites was almost the same, but the Fe-Fe(Al) distance decreased with increasing Al content. Surface analysis showed that, with increasing Al content, the content of OH groups on the mineral surface increased. The adsorption of phosphate per unit mass of Al-doped goethite increased, while adsorption per unit area decreased owing to the decrease of the relative proportion of (110) facets in the total surface area of the minerals. The results of this research facilitate better understanding of the effect of Al substitution on the structure and properties of goethite and the cycling of phosphate in the environment. PMID- 27372116 TI - Effect of non-solvent additives on the morphology, pore structure, and direct contact membrane distillation performance of PVDF-CTFE hydrophobic membranes. AB - Four common types of additives for polymer membrane preparation including organic macromolecule and micromolecule additives, inorganic salts and acids, and the strong non-solvent H2O were used to prepare poly (vinylidene fluoride-co chlorotrifluoroethylene) (PVDF-CTFE) hydrophobic flat-sheet membranes. Membrane properties including morphology, porosity, hydrophobicity, pore size and pore distribution were investigated, and the permeability was evaluated via direct contact membrane distillation (DCMD) of 3.5g/L NaCl solution in a DCMD configuration. Both inorganic and organic micromolecule additives were found to slightly influence membrane hydrophobicity. Polyethylene glycol (PEG), organic acids, LiCl, MgCl2, and LiCl/H2O mixtures were proved to be effective additives to PVDF-CTFE membranes due to their pore-controlling effects and the capacity to improve the properties and performance of the resultant membranes. The occurrence of a pre-gelation process showed that when organic and inorganic micromolecules were added to PVDF-CTFE solution, the resultant membranes presented a high interconnectivity structure. The membrane prepared with dibutyl phthalate (DBP) showed a nonporous surface and symmetrical cross-section. When H2O and LiCl/H2O mixtures were also used as additives, they were beneficial for solid-liquid demixing, especially when LiCl/H2O mixed additives were used. The membrane prepared with 5% LiCl+2% H2O achieved a flux of 24.53kg/(m(2).hr) with 99.98% salt rejection. This study is expected to offer a reference not only for PVDF CTFE membrane preparation but also for other polymer membranes. PMID- 27372117 TI - Fate and transport of the beta-adrenergic agonist ractopamine hydrochloride in soil-water systems. AB - The feed additive ractopamine hydrochloride was fortified at four concentrations into batch vials containing soils that differed in both biological activity and organic matter (OM). Sampling of the liquid layer for 14days demonstrated that ractopamine rapidly dissipated from the liquid layer. Less than 20% of the fortified dose remained in the liquid layer after 4hr, and recoveries of dosed ractopamine ranged from 8 to 18% in the liquid layer at 336hr. Sorption to soil was the major fate for ractopamine in soil:water systems, i.e., 42%-51% of the dose at 14days. The major portion of the sorbed fraction was comprised of non extractables; a smaller fraction of the sorbed dose was extracted into water and acetone, portions which would be potentially mobile in the environment. Partitioning coefficients for all soils suggested strong sorption of ractopamine to soil which is governed by hydrophobic interactions and cation exchange complexes within the soil OM. Ractopamine degradation was observed, but to mostly non-polar compounds which had a higher potential than ractopamine to sorb to soil. The formation of volatiles was also suggested. Therefore, despite rapid and extensive soil sorption, these studies indicated a portion of ractopamine, present in manures used to fertilize soils, may be mobile in the environment via water-borne events. PMID- 27372118 TI - Biosorption and retention of orthophosphate onto Ca(OH)2-pretreated biomass of Phragmites sp. AB - The biosorption of phosphorus in the form of orthophosphate (Po) from wastewater using biomass as the sorbent is of potential importance because the Po-loaded biomass could be applied in the agricultural sector as fertilizer and soil conditioner. However, biomass generally displays a very low affinity for Po sorption and therefore biomass surface modification is required. In the present study, the biomass (as model grinded leaves of Phragmites sp. were used) was pretreated with Ca(OH)2 to enhance Po biosorption capacity (qe). The results indicate that the alkaline pretreatment resulted in a modification of surface functional groups. It was concluded that the main sorption mechanisms were ligand exchange and electrostatic attraction. A series of experiments were conducted to investigate the performance of the pretreated biomass for Po uptake under various conditions. Isotherm and thermodynamic studies were also applied and analyzed. The biosorption process was best described by the pseudo-second order kinetic model and Langmuir isotherm, which gave a qmax of 12.27mgP/g at 25 degrees C and pH7. The Ca(OH)2 treated Phragmites biomass applied in this study for Po recovery may present some potential advantages in terms of costs and environmental impact. PMID- 27372119 TI - Field scale interaction and nutrient exchange between surface water and shallow groundwater in the Baiyang Lake region, North China Plain. AB - Fertilizer input for agricultural food production, as well as the discharge of domestic and industrial water pollutants, increases pressures on locally scarce and vulnerable water resources in the North China Plain. In order to: (a) understand pollutant exchange between surface water and groundwater, (b) quantify nutrient loadings, and (c) identify major nutrient removal pathways by using qualitative and quantitative methods, including the geochemical model PHREEQC) a one-year study at a wheat (Triticum aestivum L.) and maize (Zea mays L.) double cropping system in the Baiyang Lake area in Hebei Province, China, was undertaken. The study showed a high influence of low-quality surface water on the shallow aquifer. Major inflowing pollutants into the aquifer were ammonium and nitrate via inflow from the adjacent Fu River (up to 29.8mg/L NH4-N and 6.8mg/L NO3-N), as well as nitrate via vertical transport from the field surface (up to 134.8mg/L NO3-N in soil water). Results from a conceptual model show an excess nitrogen input of about 320kg/ha/a. Nevertheless, both nitrogen species were only detected at low concentrations in shallow groundwater, averaging at 3.6mg/L NH4-N and 1.8mg/L NO3-N. Measurement results supported by PHREEQC-modeling indicated cation exchange, denitrification, and anaerobic ammonium oxidation coupled with partial denitrification as major nitrogen removal pathways. Despite the current removal capacity, the excessive nitrogen fertilization may pose a future threat to groundwater quality. Surface water quality improvements are therefore recommended in conjunction with simultaneous monitoring of nitrate in the aquifer, and reduced agricultural N-inputs should be considered. PMID- 27372120 TI - Importance of storage time in mesophilic anaerobic digestion of food waste. AB - Storage was used as a pretreatment to enhance the methanization performance of mesophilic anaerobic digestion of food waste. Food wastes were separately stored for 0, 1, 2, 3, 4, 5, 7, and 12days, and then fed into a methanogenic reactor for a biochemical methane potential (BMP) test lasting up to 60days. Relative to the methane production of food waste stored for 0-1day (285-308mL/g-added volatile solids (VSadded)), that after 2-4days and after 5-12days of storage increased to 418-530 and 618-696mL/g-VSadded, respectively. The efficiency of hydrolysis and acidification of pre-stored food waste in the methanization reactors increased with storage time. The characteristics of stored waste suggest that methane production was not correlated with the total hydrolysis efficiency of organics in pre-stored food waste but was positively correlated with the storage time and acidification level of the waste. From the results, we recommend 5-7days of storage of food waste in anaerobic digestion treatment plants. PMID- 27372121 TI - Removal of ofloxacin antibiotic using heterogeneous Fenton process over modified alginate beads. AB - The aim of this work is to study the heterogeneous oxidative degradation of ofloxacin antibiotic using a composite material prepared from sodium alginate and cyclohexane dinitrilo tetraacetic acid (CDTA). The characterization tests indicated the successful incorporation of metal chelator and iron. It was also demonstrated that the synthesized beads are mesoporous. The influence of several experimental parameters (i.e.: H2O2 dose, working temperature, beads loading and initial drug concentration) on the process performances was evaluated. The reaction temperature significantly affects the drug conversion efficiency. It was also observed that the synthesized material was efficient toward the target antibiotic degradation in the presence of small quantities of hydrogen peroxide. Under optimum conditions (0.05 g of granules, initial drug concentration=10mg/L, 25MUL of 10mmol/L H2O2), conducted in a batch reaction, 94% degradation of ofloxacin was reached. The results also indicate that the composite material showed a reasonable stability; a relatively low decrease of activity after four successive runs (only 9%) and a negligible iron leaching (0.8%) have been observed. The synthesized composite material offered interesting advantages in terms of simplicity, good stability, ease of recovery from the liquid medium after use and its efficiency in the presence of low quantities of oxidant. It constitutes a good candidate in the water treatment area. PMID- 27372122 TI - Bio-remediation of acephate-Pb(II) compound contaminants by Bacillus subtilis FZUL-33. AB - Removal of Pb(2+) and biodegradation of organophosphorus have been both widely investigated respectively. However, bio-remediation of both Pb(2+) and organophosphorus still remains largely unexplored. Bacillus subtilis FZUL-33, which was isolated from the sediment of a lake, possesses the capability for both biomineralization of Pb(2+) and biodegradation of acephate. In the present study, both Pb(2+) and acephate were simultaneously removed via biodegradation and biomineralization in aqueous solutions. Batch experiments were conducted to study the influence of pH, interaction time and Pb(2+) concentration on the process of removal of Pb(2+). At the temperature of 25 degrees C, the maximum removal of Pb(2+) by B.subtilis FZUL-33 was 381.31+/-11.46mg/g under the conditions of pH5.5, initial Pb(2+) concentration of 1300mg/L, and contact time of 10min. Batch experiments were conducted to study the influence of acephate on removal of Pb(2+) and the influence of Pb(2+) on biodegradation of acephate by B.subtilis FZUL-33. In the mixed system of acephate-Pb(2+), the results show that biodegradation of acephate by B.subtilis FZUL-33 released PO4(3+), which promotes mineralization of Pb(2+). The process of biodegradation of acephate was affected slightly when the concentration of Pb(2+) was below 100mg/L. Based on the results, it can be inferred that the B.subtilis FZUL-33 plays a significant role in bio-remediation of organophosphorus-heavy metal compound contamination. PMID- 27372123 TI - Electrochemical decolorization of dye wastewater by surface-activated boron-doped nanocrystalline diamond electrode. AB - Complex organics contained in dye wastewater are difficult to degrade and often require electrochemical advanced oxidation processes (EAOPs) to treat it. Surface activation of the electrode used in such treatment is an important factor determining the success of the process. The performance of boron-doped nanocrystalline diamond (BD-NCD) film electrode for decolorization of Acid Yellow (AY-36) azo dye with respect to the surface activation by electrochemical polarization was studied. Anodic polarization found to be more suitable as electrode pretreatment compared to cathodic one. After anodic polarization, the originally H-terminated surface of BD-NCD was changed into O-terminated, making it more hydrophilic. Due to the oxidation of surface functional groups and some portion of sp(2) carbon in the BD-NCD film during anodic polarization, the electrode was successfully being activated showing lower background current, wider potential window and considerably less surface activity compared to the non polarized one. Consequently, electrooxidation (EO) capability of the anodically polarized BD-NCD to degrade AY-36 dye was significantly enhanced, capable of nearly total decolorization and chemical oxygen demand (COD) removal even after several times of re-using. The BD-NCD film electrode favored acidic condition for the dye degradation; and the presence of chloride ion in the solution was found to be more advantageous than sulfate active species. PMID- 27372124 TI - Preliminary study of acrylamide monomer decomposition during methane fermentation of dairy waste sludge. AB - Polyacrylamide (PAM) used in sludge dewatering exists widely in high-solid anaerobic digestion. Acrylamide is registered in the list of chemicals demonstrating toxic, carcinogenic and mutagenic properties. Therefore, it is reasonable to ask about the mobility of such residual substances in the environment. The study was carried out to assess the impact of the mesophilic (39+/-1 degrees C) and thermophilic (54+/-1 degrees C) fermentation process on the level of acrylamide monomer (AMD) content in the dairy sludge. The material was analysed using high-performance liquid chromatography (HPLC) for quantification of AMD. The results indicate that the process of methane fermentation continues regardless of the temperature effects on the degradation of AMD in dairy sludge. The degree of reduction of acrylamide monomer for thermophilic fermentation is 100%, while for mesophilic fermentation it is 91%. In practice, this means that biogas technology eliminates the risk of AMD migration to plant tissue. Moreover, it should be stressed that 90% of cumulative biogas and methane production was reached one week earlier under thermophilic conditions - the dynamics of the methanisation process were over 20% faster. PMID- 27372125 TI - The contribution of mediated oxidation mechanisms in the electrolytic degradation of cyanuric acid using diamond anodes. AB - In this work, the contribution of mediated oxidation mechanisms in the electrolytic degradation of cyanuric acid using boron-doped diamond (BDD) anodes was investigated in different electrolytes. A complete mineralization of cyanuric acid was obtained in NaCl; however lower degrees of mineralization of 70% and 40% were obtained in Na2SO4 and NaClO4, respectively. This can be explained by the nature of the oxidants electrogenerated in each electrolyte. It is clear that the contribution of active chlorine (Cl2, HClO, ClO(-)) electrogenerated from oxidation of chlorides on BDD is much more important in the electrolytic degradation of cyanuric acid than the persulfate and hydroxyl radicals produced by electro-oxidation of sulfate and water on BDD anodes. This could be explained by the high affinity of active chlorine towards nitrogen compounds. No organic intermediates were detected during the electrolytic degradation of cyanuric acid in any the electrolytes, which can be explained by their immediate depletion by hydroxyl radicals produced on the BDD surface. Nitrates and ammonium were the final products of electrolytic degradation of cyanuric acid on BDD anodes in all electrolytes. In addition, small amounts of chloramines were formed in the chloride medium. Low current density (<=10mA/cm(2)) and neutral medium (pH in the range 6-9) should be used for high efficiency electrolytic degradation and negligible formation of hazardous chlorate and perchlorate. PMID- 27372126 TI - Adsorptive removal of As(III) ions from water using spent grain modified by polyacrylamide. AB - In order to enhance the removal efficiency of As(III), a pre-oxidation process is generally applied first to convert As(III) to As(V), which may cause unwanted new contaminants. To overcome this problem, efforts were made to develop an effective way to remove As(III) directly without an oxidation step. The effect of polyacrylamide polymers (PAMs) such as anionic PAM, cationic PAM and nonionic PAM, on As(III) ion adsorption by spent grain (SG) was investigated. The physico chemical properties of the three PAM-polymerized SGs (APSG (anionic PAM polymerized modified spent grain), CPSG (cationic PAM-polymerized spent grain) and NPSG (nonionic PAM-polymerized spent grain)) were analyzed using Fourier transform infrared (FT-IR), scanning electron microscope (SEM) and zeta potential. Batch experimental data showed that the sequence of preferential adsorption for As(III) was APSG>CPSG>NPSG. Active functional groups such as amino group (NH2), carbonyl group (CO), C-N bond of the amide group (CONH2), and hydroxyl group (O-H) were responsible for As(III) adsorption. Many tubular structures occurring on the surface of APSG possibly increase the specific surface areas and favor the adsorption of As(III) ions. A fixed-bed study was carried out by using APSG as an adsorbent for As(III) from water. Three factors such as bed height, initial concentration and flow rate were studied, and breakthrough curves of As(III) were obtained. The Adams-Bohart model was used to analyze the experimental data and the model parameters were evaluated. PMID- 27372127 TI - Nutrient variability and its influence on nitrogen processes in a highly turbid tropical estuary (Bangpakong, Gulf of Thailand). AB - Estuarine ecosystems in SE Asia have been poorly studied when compared to other tropical environments. Important gaps exist particularly in the understanding of their biogeochemical function and contribution to global change. In this work we looked into N-turnover in the water column and sediments of the Bangpakong estuary (13 degrees N). A seasonal sampling program was performed along the salinity gradient covering different stretches of the estuary (68km). Key physical and chemical characteristics were also monitored in order to unravel possible environmental controls. Results showed the occurrence of active denitrification in sediments (5.7-50.9nmol N-N2/(cm(3).hr)), and water column (3.5-1044pmol N-N2/(cm(3).hr)). No seasonal or spatial variability was detected for denitrification potential in sediment samples. However, in the water column, the denitrification activity peaked during the transition season in the downstream sites coinciding with high turbidity levels. Therefore, in that period of the year, the water column compartment may be an important contributor to nitrate reduction within the estuary. The rather low nitrification rates detected were not always measurable, probably due to the reduced oxygen content and high siltation. This study is one of the few dealing simultaneously with sediments and water column processes in a highly turbid tropical estuary. Therefore, it emerges as a valuable contribution for the understanding of the dynamics of the nitrogen cycle in tropical environments by exploring the role of estuarine N microbial activity in reducing the effects of increased nitrogen loads. PMID- 27372128 TI - Rapid adsorption of toxic Pb(II) ions from aqueous solution using multiwall carbon nanotubes synthesized by microwave chemical vapor deposition technique. AB - Multiwall carbon nanotubes (MWCNTs) were synthesized using a tubular microwave chemical vapor deposition technique, using acetylene and hydrogen as the precursor gases and ferrocene as catalyst. The novel MWCNT samples were tested for their performance in terms of Pb(II) binding. The synthesized MWCNT samples were characterized using Fourier Transform Infrared (FT-IR), Brunauer, Emmett and Teller (BET), Field Emission Scanning Electron Microscopy (FESEM) analysis, and the adsorption of Pb(II) was studied as a function of pH, initial Pb(II) concentration, MWCNT dosage, agitation speed, and adsorption time, and process parameters were optimized. The adsorption data followed both Freundlich and Langmuir isotherms. On the basis of the Langmuir model, Qmax was calculated to be 104.2mg/g for the microwave-synthesized MWCNTs. In order to investigate the dynamic behavior of MWCNTs as an adsorbent, the kinetic data were modeled using pseudo first-order and pseudo second-order equations. Different thermodynamic parameters, viz., ?H(0), ?S(0) and ?G(0) were evaluated and it was found that the adsorption was feasible, spontaneous and endothermic in nature. The statistical analysis revealed that the optimum conditions for the highest removal (99.9%) of Pb(II) are at pH5, MWCNT dosage 0.1g, agitation speed 160r/min and time of 22.5min with the initial concentration of 10mg/L. Our results proved that microwave-synthesized MWCNTs can be used as an effective Pb(II) adsorbent due to their high adsorption capacity as well as the short adsorption time needed to achieve equilibrium. PMID- 27372129 TI - Water uptake of multicomponent organic mixtures and their influence on hygroscopicity of inorganic salts. AB - The hygroscopic behaviors of atmospherically relevant multicomponent water soluble organic compounds (WSOCs) and their effects on ammonium sulfate (AS) and sodium chloride were investigated using a hygroscopicity tandem differential mobility analyzer (HTDMA) in the relative humidity (RH) range of 5%-90%. The measured hygroscopic growth was compared with predictions from the Extended Aerosol Inorganics Model (E-AIM) and Zdanovskii-Stokes-Robinson (ZSR) method. The equal mass multicomponent WSOCs mixture containing levoglucosan, succinic acid, phthalic acid and humic acid showed gradual water uptake without obvious phase change over the whole RH range. It was found that the organic content played an important role in the water uptake of mixed particles. When organic content was dominant in the mixture (75%), the measured hygroscopic growth was higher than predictions from the E-AIM or ZSR relation, especially under high RH conditions. For mass fractions of organics not larger than 50%, the hygroscopic growth of mixtures was in good agreement with model predictions. The influence of interactions between inorganic and organic components on the hygroscopicity of mixed particles was related to the salt type and organic content. These results could contribute to understanding of the hygroscopic behaviors of multicomponent aerosol particles. PMID- 27372130 TI - Influence factors for the oxidation of pyrite by oxygen and birnessite in aqueous systems. AB - The oxidation of exposed pyrite causes acid mine drainage, soil acidification, and the release of toxic metal ions. As the important abiotic oxidants in supergene environments, oxygen and manganese oxides participate in the oxidation of pyrite. In this work, the oxidation processes of natural pyrite by oxygen and birnessite were studied in simulated systems, and the influence of pH, Fe(II) and Cr(III) on the intermediates and redox rate was investigated. SO4(2-) and elemental S were formed as the major and minor products, respectively, during the oxidation processes. Ferric (hydr) oxides including Fe(OH)3 and goethite were formed with low degree of crystallinity. Low pH and long-term reaction facilitated the formation of goethite and ferric hydroxide, respectively. The rate of pyrite oxidation by birnessite was enhanced in the presence of air (oxygen), and Fe(II) ions played a key role in the redox process. The addition of Fe(II) ions to the reaction system significantly enhanced the oxidation rate of pyrite; however, the presence of Cr(III) ions remarkably decreased the pyrite oxidation rate in aqueous systems. The introduction of Fe(II) ions to form a Fe(III)/Fe(II) redox couple facilitated the electron transfer and accelerated the oxidation rate of pyrite. The present work suggests that isolation from air and decreasing the concentration of Fe(II) ions in aqueous solutions might be effective strategies to reduce the oxidation rate of pyrite in mining soils. PMID- 27372131 TI - Effect of algal flocculation on dissolved organic matters using cationic starch modified soils. AB - Modified soils (MSs) are being increasingly used as geo-engineering materials for the sedimentation removal of cyanobacterial blooms. Cationic starch (CS) has been tested as an effective soil modifier, but little is known about its potential impacts on the treated water. This study investigated dissolved organic matters in the bloom water after algal removal using cationic starch modified soils (CS MSs). Results showed that the dissolved organic carbon (DOC) could be decreased by CS-MS flocculation and the use of higher charge density CS yielded a greater DOC reduction. When CS with the charge density of 0.052, 0.102 and 0.293meq/g were used, DOC was decreased from 3.4 to 3.0, 2.3 and 1.7mg/L, respectively. The excitation-emission matrix fluorescence spectroscopy and UV254 analysis indicated that CS-MS exhibits an ability to remove some soluble organics, which contributed to the DOC reduction. However, the use of low charge density CS posed a potential risk of DOC increase due to the high CS loading for effective algal removal. When CS with the charge density of 0.044meq/g was used, DOC was increased from 3.4 to 3.9mg/L. This study suggested, when CS-MS is used for cyanobacterial bloom removal, the content of dissolved organic matters in the treated water can be controlled by optimizing the charge density of CS. For the settled organic matters, other measures (e.g., capping treatments using oxygen loaded materials) should be jointly applied after algal flocculation. PMID- 27372132 TI - In vitro assessment of thyroid hormone receptor activity of four organophosphate esters. AB - Previous animal experiments have implied that organophosphate esters (OPEs) have a disruption effect on the thyroid endocrine system. However, knowledge of the toxicological mechanism remains limited. In this study, the activities of four OPEs have been characterized against the thyroid hormone (TH) nuclear receptor (TR) using two in vitro models, with the aim of evaluating their toxicity mechanisms towards the TR. The results of a TH-dependent cell proliferation assay showed that tris(2-chloro-1-(chloromethyl)ethyl)phosphate (TDCPP) could induce cell growth, while the other three OPEs had no effect. The results of a luciferase reporter gene assay revealed that all four of the OPEs tested in the current study showed agonistic activity towards TRbeta, with TDCPP being the most potent one. Moreover, molecular docking revealed that all the tested OPEs could fit into the ligand binding pocket of TRbeta, with TDCPP binding more effectively than the other three OPEs. Taken together, these data suggest that OPEs might disrupt the thyroid endocrine system via a mechanism involving the activation of TR. PMID- 27372133 TI - Phosphate adsorption performance of a novel filter substrate made from drinking water treatment residuals. AB - Phosphate is one of the most predominant pollutants in natural waters. Laboratory experiments were conducted to investigate the phosphate adsorption performance of a (NFS) made from drinking water treatment residuals. The adsorption of phosphate on the NFS fitted well with the Freundlich isotherm and pseudo second-order kinetic models. At pH7.0, the maximum adsorption capacity of 1.03mg/g was achieved at 15 degrees C corresponding to the wastewater temperature in cold months, and increased notably to 1.31mg/g at 35 degrees C. Under both acidic conditions (part of the adsorption sites was consumed) and basic conditions (negative charges formed on the surface of NFS, which led to a static repulsion of PO4(3-) and HPO4(2-)), the adsorption of phosphate was slightly inhibited. Further study showed that part of the adsorption sites could be recovered by 0.25mol/L NaOH. The activation energy was calculated to be above 8.0kJ/mol, indicating that the adsorption of phosphate on NFS was probably a chemical process. Considering the strong phosphate adsorption capacity and recoverability, NFS showed great promise on enhancing phosphate removal from the secondary treated wastewater in the filtration process. PMID- 27372134 TI - Oxygen tolerance capacity of upflow anaerobic solid-state (UASS) with anaerobic filter (AF) system. AB - In order to investigate the oxygen tolerance capacity of upflow anaerobic solid state (UASS) with anaerobic filter (AF) system, the effect of microaeration on thermophilic anaerobic digestion of maize straw was investigated under batch conditions and in the UASS with AF system. Aeration intensities of 0-431mL O2/gvs were conducted as pretreatment under batch conditions. Aeration pretreatment obviously enhanced anaerobic digestion and an aeration intensity of 431mL O2/gvs increased the methane yield by 82.2%. Aeration intensities of 0-355mL O2/gvs were conducted in the process liquor circulation of the UASS with AF system. Dissolved oxygen (DO) of UASS and AF reactors kept around 1.39+/-0.27 and 0.99+/-0.38mg/L, respectively. pH was relatively stable around 7.11+/-0.04. Volatile fatty acids and soluble chemical oxygen demand concentration in UASS reactor were higher than those in AF reactor. Methane yield of the whole system was almost stable at 85+/ 7mL/gvs as aeration intensity increased step by step. The UASS with AF system showed good oxygen tolerance capacity. PMID- 27372135 TI - Response of soil CO2 efflux to precipitation manipulation in a semiarid grassland. AB - Soil CO2 efflux (SCE) is an important component of ecosystem CO2 exchange and is largely temperature and moisture dependent, providing feedback between C cycling and the climate system. We used a precipitation manipulation experiment to examine the effects of precipitation treatment on SCE and its dependences on soil temperature and moisture in a semiarid grassland. Precipitation manipulation included ambient precipitation, decreased precipitation (-43%), or increased precipitation (+17%). The SCE was measured from July 2013 to December 2014, and CO2 emission during the experimental period was assessed. The response curves of SCE to soil temperature and moisture were analyzed to determine whether the dependence of SCE on soil temperature or moisture varied with precipitation manipulation. The SCE significantly varied seasonally but was not affected by precipitation treatments regardless of season. Increasing precipitation resulted in an upward shift of SCE-temperature response curves and rightward shift of SCE moisture response curves, while decreasing precipitation resulted in opposite shifts of such response curves. These shifts in the SCE response curves suggested that increasing precipitation strengthened the dependence of SCE on temperature or moisture, and decreasing precipitation weakened such dependences. Such shifts affected the predictions in soil CO2 emissions for different precipitation treatments. When considering such shifts, decreasing or increasing precipitation resulted in 43 or 75% less change, respectively, in CO2 emission compared with changes in emissions predicted without considering such shifts. Furthermore, the effects of shifts in SCE response curves on CO2 emission prediction were greater during the growing than the non-growing season. PMID- 27372136 TI - Identifying the major fluorescent components responsible for ultrafiltration membrane fouling in different water sources. AB - Three-dimensional fluorescence excitation-emission matrix (EEM) coupled with parallel factor analysis (PARAFAC) was performed for a total of 18 water samples taken from three water sources (two lakes and one wastewater treatment plant (WWTP) secondary effluent), with the purpose of identifying the major ultrafiltration (UF) membrane foulants in different water sources. Three fluorescent components (C1, C2 and C3) were identified, which represented terrestrially derived humic-like substances (C1), microbially derived humic-like substances (C2), and protein-like substances (C3). The correlations between the different fluorescent components and UF membrane fouling were analyzed. It was shown that for the WWTP secondary effluent, all three components (C1, C2 and C3) made a considerable contribution to the irreversible and total fouling of the UF membrane. However, for the two lakes, only the C3 exhibited a strong correlation with membrane fouling, indicating that the protein-like substances were the major membrane foulants in the lake waters. Significant attachment of C1, C2 and C3 to the UF membrane was also confirmed by mass balance analyses for the WWTP secondary effluent; while the attachment of C1 and C2 was shown to be negligible for the two lakes. The results may provide basic formation for developing suitable fouling control strategies for sustainable UF processes. PMID- 27372137 TI - Remediation of saline-sodic soil with flue gas desulfurization gypsum in a reclaimed tidal flat of southeast China. AB - Salinization and sodicity are obstacles for vegetation reconstruction of coastal tidal flat soils. A study was conducted with flue gas desulfurization (FGD) gypsum applied at rates of 0, 15, 30, 45 and 60Mg/ha to remediate tidal flat soils of the Yangtze River estuary. Exchangeable sodium percentage (ESP), exchangeable sodium (ExNa), pH, soluble salt concentration, and composition of soluble salts were measured in 10cm increments from the surface to 30cm depth after 6 and 18months. The results indicated that the effect of FGD-gypsum is greatest in the 0-10cm mixing soil layer and 60Mg/ha was the optimal rate that can reduce the ESP to below 6% and decrease soil pH to neutral (7.0). The improvement effect was reached after 6months, and remained after 18months. The composition of soluble salts was transformed from sodic salt ions mainly containing Na(+), HCO3(-)+CO3(2-) and Cl(-) to neutral salt ions mainly containing Ca(2+) and SO4(2-). Non-halophyte plants were survived at 90%. The study demonstrates that the use of FGD-gypsum for remediating tidal flat soils is promising. PMID- 27372138 TI - Occurrence, distribution, and potential influencing factors of sewage sludge components derived from nine full-scale wastewater treatment plants of Beijing, China. AB - Millions of tons of waste activated sludge (WAS) produced from biological wastewater treatment processes cause severe adverse environmental consequences. A better understanding of WAS composition is thus very critical for sustainable sludge management. In this work, the occurrence and distribution of several fundamental sludge constituents were explored in WAS samples from nine full-scale wastewater treatment plants (WWTPs) of Beijing, China. Among all the components investigated, active heterotrophic biomass was dominant in the samples (up to 9478mg/L), followed by endogenous residues (6736mg/L), extracellular polymeric substances (2088mg/L), and intracellular storage products (464mg/L) among others. Moreover, significant differences (p<0.05) were observed in composition profiles of sludge samples among the studied WWTPs. To identify the potential parameters affecting the variable fractions of sludge components, wastewater source as well as design and operational parameters of WWTPs were studied using statistical methods. The findings indicated that the component fraction of sewage sludge depends more on wastewater treatment alternatives than on wastewater characteristics among other parameters. A principal component analysis was conducted, which further indicated that there was a greater proportion of residual inert biomass in the sludge produced by the combined system of the conventional anaerobic/anoxic/oxic process and a membrane bioreactor. Additionally, a much longer solids retention time was also found to influence the sludge composition and induce an increase in both endogenous inert residues and extracellular polymeric substances in the sludge. PMID- 27372139 TI - Two-step fast microwave-assisted pyrolysis of biomass for bio-oil production using microwave absorbent and HZSM-5 catalyst. AB - A novel technology of two-step fast microwave-assisted pyrolysis (fMAP) of corn stover for bio-oil production was investigated in the presence of microwave absorbent (SiC) and HZSM-5 catalyst. Effects of fMAP temperature and catalyst-to biomass ratio on bio-oil yield and chemical components were examined. The results showed that this technology, employing microwave, microwave absorbent and HZSM-5 catalyst, was effective and promising for biomass fast pyrolysis. The fMAP temperature of 500 degrees C was considered the optimum condition for maximum yield and best quality of bio-oil. Besides, the bio-oil yield decreased linearly and the chemical components in bio-oil were improved sequentially with the increase of catalyst-to-biomass ratio from 1:100 to 1:20. The elemental compositions of bio-char were also determined. Additionally, compared to one-step fMAP process, two-step fMAP could promote the bio-oil quality with a smaller catalyst-to-biomass ratio. PMID- 27372140 TI - New insight into adsorption characteristics and mechanisms of the biosorbent from waste activated sludge for heavy metals. AB - The adsorption characteristics and mechanisms of the biosorbent from waste activated sludge were investigated by adsorbing Pb(2+) and Zn(2+) in aqueous single-metal solutions. A pH value of the metal solutions at 6.0 was beneficial to the high adsorption quantity of the biosorbent. The optimal mass ratio of the biosorbent to metal ions was found to be 2. A higher adsorption quantity of the biosorbent was achieved by keeping the reaction temperature below 55 degrees C. Response surface methodology was applied to optimize the biosorption processes, and the developed mathematical equations showed high determination coefficients (above 0.99 for both metal ions) and insignificant lack of fit (p=0.0838 and 0.0782 for Pb(2+) and Zn(2+), respectively). Atomic force microscopy analyses suggested that the metal elements were adsorbed onto the biosorbent surface via electrostatic interaction. X-ray photoelectron spectroscopy analyses indicated the presence of complexation (between -NH2, -CN and metal ions) and ion-exchange (between -COOH and metal ions). The adsorption mechanisms could be the combined action of electrostatic interaction, complexation and ion-exchange between functional groups and metal ions. PMID- 27372141 TI - Volatile organic compound emissions from straw-amended agricultural soils and their relations to bacterial communities: A laboratory study. AB - A laboratory study was conducted to investigate volatile organic compound (VOC) emissions from agricultural soil amended with wheat straw and their associations with bacterial communities for a period of 66days under non-flooded and flooded conditions. The results indicated that ethene, propene, ethanol, i-propanol, 2 butanol, acetaldehyde, acetone, 2-butanone, 2-pentanone and acetophenone were the 10 most abundant VOCs, making up over 90% of the total VOCs released under the two water conditions. The mean emission of total VOCs from the amended soils under the non-flooded condition (5924ng C/(kg.hr)) was significantly higher than that under the flooded condition (2211ng C/(kg.hr)). One "peak emission window" appeared at days 0-44 or 4-44, and over 95% of the VOC emissions occurred during the first month under the two water conditions. Bacterial community analysis using denaturing gradient gel electrophoresis (DGGE) showed that a relative increase of Actinobacteria, Bacteroidetes, Firmicutes and gamma-Proteobacteria but a relative decrease of Acidobacteria with time were observed after straw amendments under the two water conditions. Cluster analysis revealed that the soil bacterial communities changed greatly with incubation time, which was in line with the variation of the VOC emissions over the experimental period. Most of the above top 10 VOCs correlated positively with the predominant bacterial species of Bacteroidetes, Firmicutes and Verrucomicrobia but correlated negatively with the dominant bacterial species of Actinobacteria under the two water conditions. These results suggested that bacterial communities might play an important role in VOC emissions from straw-amended agricultural soils. PMID- 27372142 TI - [Characteristics of human metapneumovirus infection, is it important the age?] PMID- 27372143 TI - [Diagnostic microbiology in mastitis. What do we know about counts and significant microorganisms?] PMID- 27372144 TI - Microbiological findings in burn patients treated in a general versus a designated intensive care unit: Effect on length of stay. AB - BACKGROUND: Infection is one of the most common causes of mortality and morbidity in burn patients. The incidence and frequency of microbiological micro-organisms are known to vary across different models of intensive care units. To date, no study has attempted to describe the different findings in burn patients treated in an open, general intensive care unit (GICU) versus a dedicated burns intensive care unit (BICU). Only limited data is available on the effect of these microbiological micro-organisms on patients' length of stay. AIM: To characterize and compare the microbiological flora and antibiotic resistance patterns encountered in two different models of burn intensive care and to determine the effect of specific microbiological types on length of intensive care unit (ICU) and overall stay. METHODS: A retrospective case-control study of 209 burn patients treated in two highly specialized, Western burn referral centres between September 2009 and March 2014. RESULTS: 9710 culture results were analysed, of which 2590 (26.7%) yielded positive results (1537 in the GICU and 1050 in the BICU). Gram-positive cultures were more frequently found in the GICU, whereas Gram-negative and yeast cultures were more prevalent in the BICU. The most frequently encountered micro-organisms in both units were similar and included Staphylococcus aureus, Pseudomonas aeruginosa, coagulase-negative staphylococci (CoNS) and Candida albicans. Significantly more resistant bacteria were detected in the BICU. Testing positive across all types of microbiological isolates, as well as for both Gram-positive and -negative bacteria significantly prolonged patient length of stay. This effect was even more pronounced if the micro organisms were resistant to antimicrobial therapy. CONCLUSION: There are notable differences in the microbiological isolate and antibiotic resistance patterns between burn patients treated in a GICU compared to a designated BICU. In both units, testing positive for resistant microbiological micro-organisms is significantly associated with longer hospital stay. PMID- 27372145 TI - Response to Letter to the Editor "A new method for scar tissue assessment: Modified POSAS observer scale". PMID- 27372146 TI - Sarcopenia and sarcopenic obesity in patients with complex abdominal wall hernias. AB - BACKGROUND: Chronic muscle wasting, or sarcopenia, has been associated with poor health outcomes after major surgical procedures. Here, we explore the utility of CT-generated determinations of sarcopenia as markers of risk in patients undergoing evaluation for complex ventral hernia repair. METHODS: In 148 successive patients being evaluated for complex ventral hernia repair, CT scans were analyzed retrospectively for attributes of the hernia and indices of core muscle mass, correlating them with preoperative clinical/laboratory profiles and outcomes in 82 patients who had undergone surgery. RESULTS: Prevalence of sarcopenia, and sarcopenia corrected for obesity, was 26% and 20% respectively. Sarcopenia was associated with age, some laboratory indicators, and increased hospital length of stay but not with a higher likelihood of surgical site occurrence. CONCLUSIONS: Obesity may obscure the value of sarcopenia as a marker of metabolic disturbance and postoperative outcome. Image-based measurements of core-muscle mass should be used with caution as predictors of risk in similar surgical populations. PMID- 27372147 TI - Frame-of-reference training for simulation-based intraoperative communication assessment. AB - BACKGROUND: The purpose of this study was to examine the impact of frame-of reference (FOR) training on assessments of intraoperative communication skills and identify areas of need to inform curricular efforts. METHODS: Simulation instructors (M.D., Ph.D., Research Fellow, Simulation Technician) underwent a 2 hour FOR training session with the operating room communication instrument. They then independently rated communication skills of 19 PGY1s who participated in a team-based simulation. Residents completed self-assessments via video review of the scenario. Intraclass correlation coefficients were used to examine inter rater reliability. Relationships between trained raters and resident scores were assessed with Pearson correlation coefficients and paired sample t tests. RESULTS: Inter-reliability after FOR training was .91. The correlation between trained rater scores and resident evaluations was nonsignificant. Residents significantly underestimated their intraoperative communication skills (P < .05). Use of names, closed loop communication, and sharing information with team members demonstrated consistently low ratings among all residents. CONCLUSIONS: These findings reveal that a number of individuals can be trained to reliably rate resident intraoperative communication performance and that residents tend to under-rate their communication skills. PMID- 27372148 TI - Bioanalytical challenge: A review of environmental and pharmaceuticals contaminants in human milk. AB - An overview of bioanalytical methods for the determination of environmental and pharmaceutical contaminants in human milk is presented. The exposure of children to these contaminants through lactation has been widely investigated. The human milk contains diverse proteins, lipids, and carbohydrates and the concentration of these components is drastically altered during the lactation period providing a high degree of an analytical challenge. Sample collection and pretreatment are still considered the Achilles' heel. This review presents liquid chromatographic methods developed in the last 10 years for this complex matrix with focuses in the extraction and quantification steps. Green sample preparation protocols have been emphasized. PMID- 27372149 TI - Corrigendum to "Sonicating multi-lumen sliced catheter tips after the roll-plate technique improves the detection of catheter colonization in adults" [J. Microbiol. Methods 122 (2016) 20-22]. PMID- 27372150 TI - Reduction in Clostridium difficile infection associated with the introduction of hydrogen peroxide vapour automated room disinfection. AB - The clinical impact of implementing hydrogen peroxide vapour (HPV) disinfection of rooms vacated by patients with Clostridium difficile infection (CDI) was evaluated. Breakpoint time series analysis indicated a significant reduction (P<0.001) in the CDI rate at the time when HPV disinfection was implemented, resulting in a reduction in the CDI rate from 1.0 to 0.4 cases per 1000 patient days in the 24 months before HPV usage compared with the first 24 months of HPV usage. HPV should be considered to augment the terminal disinfection of rooms vacated by patients with CDI. PMID- 27372151 TI - Quali-quantitative analysis of the phenolic fraction of the flowers of Corylus avellana, source of the Italian PGI product "Nocciola di Giffoni": Isolation of antioxidant diarylheptanoids. AB - There is only limited information available on the chemical composition of the non-edible parts of Corylus avellana, source of the Italian PGI product "Nocciola di Giffoni" (hazelnut). An initial LC-MS profile of the methanolic extract of the male flowers of C. avellana, cultivar 'Tonda di Giffoni' led to the isolation of 12 compounds, of which the structures were elucidated by NMR spectroscopy. These were identified as three previously undescribed diarylheptanoids, named giffonins Q-S, along with nine known compounds. Furthermore, the quantitative determination of the main compounds occurring in the methanolic extract of C. avellana flowers was carried out by an analytical approach based on LC-ESI(QqQ)MS, using the Multiple Reaction Monitoring (MRM) experiment. In order to explore the antioxidant ability of C. avellana flowers, the methanolic extract and the isolated compounds were evaluated for their inhibitory effects on human plasma lipid peroxidation induced by H2O2 and H2O2/Fe(2+), by measuring the concentration of TBARS. PMID- 27372152 TI - Prevention policies addressing packaging and packaging waste: Some emerging trends. AB - Packaging waste is a major issue in several countries. Representing in industrialized countries around 30-35% of municipal solid waste yearly generated, this waste stream has steadily grown over the years even if, especially in Europe, specific recycling and recovery targets have been fixed. Therefore, an increasing attention starts to be devoted to prevention measures and interventions. Filling a gap in the current literature, this explorative paper is a first attempt to map the increasingly important phenomenon of prevention policies in the packaging sector. Through a theoretical sampling, 11 countries/states (7 in and 4 outside Europe) have been selected and analyzed by gathering and studying primary and secondary data. Results show evidence of three specific trends in packaging waste prevention policies: fostering the adoption of measures directed at improving packaging design and production through an extensive use of the life cycle assessment; raising the awareness of final consumers by increasing the accountability of firms; promoting collaborative efforts along the packaging supply chains. PMID- 27372153 TI - The economic value of increasing geospatial access to tetanus toxoid immunization in Mozambique. AB - BACKGROUND: With tetanus being a leading cause of maternal and neonatal morbidity and mortality in low and middle income countries, ensuring that pregnant women have geographic access to tetanus toxoid (TT) immunization can be important. However, immunization locations in many systems may not be placed to optimize access across the population. Issues of access must be addressed for vaccines such as TT to reach their full potential. METHODS: To assess how TT immunization locations meet population demand in Mozambique, our team developed and utilized SIGMA (Strategic Integrated Geo-temporal Mapping Application) to quantify how many pregnant women are reachable by existing TT immunization locations, how many cannot access these locations, and the potential costs and disease burden of not covering geographically harder-to-reach populations. Sensitivity analyses covered a range of catchment area sizes to include realistic travel distances and to determine the area some locations would need to cover in order for the existing system to reach at least 99% of the target population. RESULTS: For 99% of the population to reach health centers, people would be required to travel up to 35km. Limiting this distance to 15km would result in 5450 (3033-7108) annual cases of neonatal tetanus that could be prevented by TT, 144,240 (79,878-192,866) DALYs, and $110,691,979 ($56,180,326-$159,516,629) in treatment costs and productivity losses. A catchment area radius of 5km would lead to 17,841 (9929 23,271) annual cases of neonatal tetanus that could be prevented by TT, resulting in 472,234 (261,517-631,432) DALYs and $362,399,320 ($183,931,229-$522,248,480) in treatment costs and productivity losses. CONCLUSION: TT immunization locations are not geographically accessible by a significant proportion of pregnant women, resulting in substantial healthcare and productivity costs that could potentially be averted by adding or reconfiguring TT immunization locations. The resulting cost savings of covering these harder to reach populations could help pay for establishing additional immunization locations. PMID- 27372154 TI - Mumps-specific cross-neutralization by MMR vaccine-induced antibodies predicts protection against mumps virus infection. AB - BACKGROUND: Similar to other recent mumps genotype G outbreaks worldwide, most mumps patients during the recent mumps genotype G outbreaks in the Netherlands had received 2 doses of measles, mumps and rubella (MMR) vaccine during childhood. Here, we investigate the capacity of vaccine-induced antibodies to neutralize wild type mumps virus strains, including mumps virus genotype G. METHODS: In this study, we tested 105 pre-outbreak serum samples from students who had received 2 MMR vaccine doses and who had no mumps virus infection (n=76), symptomatic mumps virus infection (n=10) or asymptomatic mumps virus infection (n=19) during the mumps outbreaks. In all samples, mumps-specific IgG concentrations were measured by multiplex immunoassay and neutralization titers were measured against the Jeryl Lynn vaccine strain and against wild type genotype G and genotype D mumps virus strains. RESULTS: The correlation between mumps-specific IgG concentrations and neutralization titers against Jeryl Lynn was poor, which suggests that IgG concentrations do not adequately represent immunological protection against mumps virus infection by antibody neutralization. Pre-outbreak neutralization titers in infected persons were significantly lower against genotype G than against the vaccine strain. Furthermore, antibody neutralization of wild type mumps virus genotype G and genotype D was significantly reduced in pre-outbreak samples from infected persons as compared with non-infected persons. No statistically significant difference was found for the vaccine strain. The sensitivity/specificity ratio was largest for neutralization of the genotype G strain as compared with the genotype D strain and the vaccine strain. CONCLUSIONS: The reduced neutralization of wild type mumps virus strains in MMR vaccinated persons prior to infection indicates that pre-outbreak mumps virus neutralization is partly strain-specific and that neutralization differs between infected and non-infected persons. Therefore, we recommend the use of wild type mumps virus neutralization assays as preferred tool for surveillance of protection against mumps virus infection. PMID- 27372155 TI - PLGA-microencapsulation protects Salmonella typhi outer membrane proteins from acidic degradation and increases their mucosal immunogenicity. AB - Salmonella (S.) enterica infections are an important global health problem with more than 20 million individuals suffering from enteric fever annually and more than 200,000 lethal cases per year. Although enteric fever can be treated appropriately with antibiotics, an increasing number of antibiotic resistant Salmonella strains is detected. While two vaccines against typhoid fever are currently on the market, their availability in subtropical endemic areas is limited because these products need to be kept in uninterrupted cold chains. Hence, the development of a thermally stable vaccine that induces mucosal immune responses would greatly improve human health in endemic areas. Here, we have combined the high structural stability of Salmonella typhi outer membrane proteins (porins) with their microencapsulation into poly(lactic-co-glycolic acid) (PLGA) to generate an orally applicable vaccine. Encapsulated porins were protected from acidic degradation and exhibited enhanced immunogenicity following oral administration. In particular, the vaccine elicited strong S. typhi-specific B cell responses in Peyer's patches and mesenteric lymph nodes. In sum, PLGA microencapsulation substantially improved the efficacy of oral vaccination against S. typhi. PMID- 27372157 TI - Response to commentary re 'Is glans penis width a risk factor for complications after hypospadias repair?'. PMID- 27372156 TI - Transmission-blocking activity is determined by transmission-reducing activity and number of control oocysts in Plasmodium falciparum standard membrane-feeding assay. AB - Malaria transmission-blocking vaccines (TBVs) are potentially helpful tools for malaria eradication. The standard membrane-feeding assay (SMFA) is considered one of the "gold standard" assays for TBV development. However, lack of consensus in reporting results from SMFA has made it very challenging to compare results from different studies. Two main readouts, % inhibition in mean oocyst count per mosquito (TRA) and % inhibition in prevalence of infected mosquitoes (TBA), have been used widely. In this study, we statistically modeled the oocyst data in SMFA using data from 105 independent feeding experiments including 9804 mosquitoes. The model was validated using an independent data set that included 10,790 mosquitoes from 110 feeding studies. The model delineates a relationship between TRA, the mean oocyst count in the control mosquitoes (mo-contl), and TBA. While TRA was independent from mo-contl, TBA values changed depending on mo-contl. Regardless of monoclonal or polyclonal antibodies tested, there were strong concordances between observed TBA and predicted TBA based on the model using mo contl and observed TRA. Simulations showed that SMFA with lower true control means had increased uncertainty in TRA estimates. The strong linkage between TBA, TRA and mo-contl inspired creation of a standardized TBA, a model-based TBA standardized to a target control mean, which allows comparison across multiple feeds regardless of mo-contl. This is the first study showing that the observed TBA can be reasonably predicted by mo-contl and the TRA of the test antibody using independent experimental data. This study indicates that TRA should be used to compare results from multiple feeds with different levels of mo-contl. If a measure of TBA is desired, it is better to report standardized TBA rather than observed TBA. These recommendations support rational comparisons of results from different studies, thus benefiting future TBV development. PMID- 27372158 TI - Spontaneous regression of suspected cystic dysplasia of the rete testis in three neonates. AB - INTRODUCTION: Cystic dysplasia of the rete testis (CDRT) is a rare cause of scrotal swelling during infancy. It is a benign lesion that is often associated with ipsilateral renal, ureteral or genital abnormalities. Leissring and Oppenheimer described it for the first time in 1973. CASE REPORTS: Since 2006, three neonates were referred to our pediatric surgery department because of a scrotal swelling related to intra-testicular cysts. Physical examination showed enlarged testicles without pain or inflammation. The ultrasound scan (USS) showed enlarged testicles related to multiple small cysts surrounded by normal parenchyma, and no other urinary abnormalities. As CDRT was suspected, a conservative strategy was proposed with repeated clinical examinations and USS. The cysts gradually regressed and disappeared in all cases, with a mean follow-up of 52 months. DISCUSSION: As reported by Jeyaratnam et al., mean age at presentation was around 6 years. The most frequently associated urinary abnormalities were renal agenesis and multicystic dysplasia of the kidney. Differential diagnosis of CDRT included single testicular cyst, epidermoid cyst, albugina cyst, teratoma, cystic lymphangioma, testicular juvenile granulosa cell tumor, cystic transformation after orchitis, or spermatic cord torsion. Ultrasonography was the method of choice for the diagnosis of CDRT and its follow up. The USS showed multiple small cysts with normal, but compressed, surrounding testicular parenchyma. A high-frequency transducer was mandatory to exclude other causes of scrotal swelling. With the involution of the cysts, the aspect of the parenchyma could be slightly heterogeneous or confused with microlithiasis. Historically, orchidectomy was the proposed treatment. However, because of a more precise diagnosis with USS, a conservative approach has been proposed. Nonetheless, recurrence after sparing surgery was frequent, as reported by many authors. Non-surgical management was reported in selected cases, sometimes after a surgical biopsy to confirm a benign lesion. Spontaneous regression of CDRT without any sequelae has been reported in six cases (see Summary Table) but long term follow-up in the adult population has never been published. Limitations of the present series were related to the small number of cases, the absence of follow-up beyond puberty, and the absence of biopsy to confirm the diagnosis of CDRT. CONCLUSION: Spontaneous regression of CDRT was possible, and conservative attitude was an option, as CDRT is a benign lesion. Careful and prolonged 'watch and wait' management was a safe alternative to surgery, but other causes of scrotal swelling must be excluded, possibly with a testicular biopsy. PMID- 27372159 TI - Disinfection Efficacy of Current Regenerative Endodontic Protocols in Simulated Necrotic Immature Permanent Teeth. AB - INTRODUCTION: The lack of mechanical debridement and reduced concentrations suggested for chemical debridement to maintain stem cell viability call into question the disinfection efficacy of current regenerative protocols. Current protocols vary in the concentration and type of antibiotic medicaments used. The aim of this study was to determine if simulated immature teeth infected with Enterococcus faecalis can be completely disinfected by following current standardized regenerative protocols and to evaluate the probable effects of residual bacteria on stem cell toxicity. METHODS: Sixty-eight caries-free maxillary incisors were used. S1 sampling protocols were validated in both negative and positive control groups via culture, scanning electron microscopy, and confocal laser scanning microscopy. All teeth, except the negative controls, were inoculated with E. faecalis. The teeth were divided into the following groups: group 1, triple antibiotic paste (ciprofloxacin:metronidazole:minocycline) at concentrations of 10, 1, and 0.1 mg/mL; group 2, double antibiotic paste (ciprofloxacin:metronidazole) at concentrations of 10, 1, and 0.1 mg/mL; group 3: Ultracal XS calcium hydroxide (Ultradent, St Louis, MO); and controls, negative and positive controls. Current regenerative protocols recommended by the American Association of Endodontists were followed. S2 sampling was performed after 4 weeks and tested for bacterial presence via culturing, scanning electron microscopy, and confocal laser scanning microscopic analysis. RESULTS: The data showed that calcium hydroxide and the current recommended antibiotic concentrations are not capable of completely eliminating bacteria from simulated necrotic immature permanent teeth. CONCLUSIONS: Overall, this study focuses on the need to re-evaluate the balance between stem cell toxicity and bacterial elimination in order to determine the appropriate concentrations and medicaments for successful regenerative endodontic procedures. PMID- 27372160 TI - Evaluation of the Effect of Rotary Systems on Stresses in a New Testing Model Using a 3-Dimensional Printed Simulated Resin Root with an Oval-shaped Canal: A Finite Element Analysis Study. AB - INTRODUCTION: This finite element analysis study was aimed at evaluating the effects of rotary systems on stresses in photopolymerized resin root models with oval-shaped canals. METHODS: Among the data collected by computed tomographic imaging, a mandibular second premolar tooth with an oval-shaped canal was selected, recorded as Digital Imaging and Communications in Medicine, and transferred to Materialise's Interactive Medical Image Control System software. Three-dimensional modeling was performed to produce photopolymerized resin root models. Root canals were prepared by OneShape (OS; MicroMega, Besancon, France); ProTaper Universal (PTU; Dentsply Tulsa Dental, Tulsa, OK); WaveOne (WO, Dentsply Maillefer, Ballaigues, Switzerland); Mtwo (MT; VDW, Munich, Germany); Twisted File (TF; Kerr Dental, Orange, CA); ProTaper Next (PTN, Dentsply Tulsa Dental), and hand files (HFs) (control). The models were scanned (micro-computed tomographic imaging; SkyScan 1174; Kontich, Belgium), finite element analysis models were created, and stresses were calculated under 300-N loading (at a 45 degrees angle and vertically). RESULTS: The maximum stress values were found to be higher when the roots were loaded at an angle. The range of the stress values was PTU > MT > WO > HF > PTN > OS > TF. The stresses were forwarded toward the apical area in the PTN, OS, and TF models. When loaded vertically, the highest maximum stress values were recorded in the WO model. High stress concentrations were observed at coronal, thus less stress was forwarded toward the apical, giving an advantage to the root. The range of the others was as follows: PTN >= PTU > MT > TF > OS >= HF. The TF model showed lower maximum stress values, whereas the HF model showed more homogenous stress distribution. CONCLUSIONS: Considering the stress distributions and stress values within the models, it can be concluded that oval-shaped canals prepared by HFs and WO were less likely to result in root fracture. PMID- 27372161 TI - Bacteremia after Endodontic Procedures in Patients with Heart Disease: Culture and Molecular Analyses. AB - INTRODUCTION: Infective endocarditis (IE) is still associated with high mortality, and antibiotic prophylaxis strategies are under intense debate. We evaluated the incidence of bacteremia after root canal preparation in teeth with necrotic pulps and apical periodontitis. METHODS: Blood samples were taken before and 5 and 30 minutes after endodontic treatment in teeth with apical periodontitis from individuals at high (n = 21) or no risk (n = 11) for IE. The former received prophylactic antibiotic therapy. Bacteriologic samples were taken from root canals before chemomechanical preparation to confirm pulp infection. Samples were subjected to aerobic and anaerobic culture and quantitative real time polymerase chain reaction (qPCR), the latter to determine the total bacterial and streptococcal levels. RESULTS: Culture revealed no bacteremia in all individuals. Analysis by qPCR showed that bacterial DNA occurred in all root canal samples. qPCR showed a similar incidence of bacteremia between patients who received or did not receive prophylactic antibiotic therapy (P > .05). In blood samples taken 5 minutes after endodontic procedures, bacteria were detected in 2 of 11 (18%) individuals not taking antibiotics and in 4 of 21 (19%) patients under prophylaxis. After 30 minutes, the incidence of bacteremia decreased to 2 of 21 (10%) in patients taking antibiotics and was undetectable in patients at no risk of IE. The incidence of bacteremia by streptococci was identical as that for total bacteria. CONCLUSIONS: No detectable bacteremia was evident by culture after treatment of infected root canals. Molecular analysis revealed bacterial DNA and streptococci in blood from some patients without a significant difference between individuals receiving or not receiving antibiotic prophylaxis. PMID- 27372162 TI - Ability of Cone-beam Computed Tomography to Detect Periapical Lesions That Were Not Detected by Periapical Radiography: A Retrospective Assessment According to Tooth Group. AB - INTRODUCTION: The detection of periapical lesions by periapical radiography (PR) can be hampered by structural noise, the impact of which differs among tooth groups. The aim of this study was to investigate the ability of cone-beam computed tomographic (CBCT) imaging to detect periapical lesions that could not be detected with PR according to tooth group. METHODS: This study retrospectively evaluated teeth that (1) had previously undergone root canal treatment (178 teeth from 86 patients), (2) had coincidentally been located within the field of view of CBCT scans performed for endodontic reasons, and (3) had also been examined with PR. The teeth of interest for the CBCT examinations were excluded to avoid sampling bias. Two dentists evaluated both the CBCT and PR images for periapical lesions. The McNemar test was used to compare the ability of CBCT imaging and PR to identify periapical lesions (alpha = 0.05). RESULTS: The overall periapical lesion detection rates of PR and CBCT imaging were 31.5% and 52.2%, respectively (P < .0001). The ability of CBCT imaging to identify periapical lesions that were not detected by PR was statistically significant for the maxillary incisors/canines (P < .0001) and maxillary molars (P < .005). CONCLUSIONS: Within the limitations of this investigation, it can be concluded that CBCT imaging is effective at detecting periapical lesions that cannot be detected on PR, particularly in the maxillary incisors/canines and molars. Our findings suggest that the influence of structural noise in the maxillary anterior region and maxillary posterior region should not be overlooked during the interpretation of PR images. PMID- 27372163 TI - The dual role of ROS, antioxidants and autophagy in cancer. AB - In this issue of the Biomedical Journal, we highlight a review revealing that the effect of autophagy, reactive oxygen species, and antioxidants in cancer may be a question of timing and context. We also discuss original research showing that the prevalence of cleft lip with or without palate in Taiwan has declined over the past 20 years, and what this might mean in terms of trends in abortion. Finally, we also learn about risk factors for recurrent hospital-acquired infection with multi-drug resistant bacteria, and the value of dental screening for patients with tinnitus. PMID- 27372164 TI - Honoring antiparasitics: The 2015 Nobel Prize in Physiology or Medicine. AB - Protozoa and helminths are the two main groups that cause parasitic diseases with a broad spectrum of clinical symptoms. Protozoa are unicellular organisms like the malaria parasite Plasmodium, which is responsible for the majority of deaths associated with parasitic infections. Helminths are alternative parasites that can produce debilitating diseases in hosts, some of which result in chronic infections. The discovery of effective therapeutic drugs is the key to improving health in regions of poverty and poor sanitation where these parasites usually occur. It is very encouraging that the 2015 Nobel Prize in Physiology or Medicine was awarded to Youyou Tu as well as William C. Campbell and Satoshi Omura for their considerable contributions in discovering artemisinin and avermectin, respectively. Both drugs revolutionized therapies for filariasis and malaria, significantly reducing by large percentages their morbidity and mortality. PMID- 27372166 TI - Clinical applications of spectral domain optical coherence tomography in retinal diseases. AB - Optical coherence tomography (OCT) was introduced about two decades ago and has revolutionized ophthalmic practice in recent years. It is a noninvasive noncontact imaging modality that provides a high-resolution cross-sectional image of the cornea, retina, choroid and optic nerve head, analogous to that of the histological section. Advances in OCT technology in signal detection technique from time-domain (TD) to spectral-domain (SD) detection have given us the potential to study various retinal layers more precisely and in less time. SD-OCT better delineates structural changes and fine lesions in the individual retinal layers. Thus, we have gained substantial information about the pathologic and structural changes in ocular conditions with primary or secondary retinal involvement. This review we discuss the clinical application of currently available SD-OCT in various retinal pathologies. Furthermore, highlights the benefits of SD-OCT over TD. With the introduction of enhanced depth imaging and swept - source OCT visualization of the choroid and choriocapillaris has become possible. Therefore, OCT has become an indispensable ancillary test in the diagnosis and management of diseases involving the retina and/or the choroid. As OCT technology continues to develop further it will provide new insights into the retinal and choroidal structure and the pathogenesis of posterior segment of the eye. PMID- 27372167 TI - Continuous epidermal growth factor receptor-tyrosine kinase inhibitor administration in primary lung adenocarcinoma patients harboring favorable mutations with controlled target lung tumors dose not hinder survival benefit despite small new lesions. AB - BACKGROUND: In this study, we investigated the efficacy of continuous epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) administration in lung adenocarcinoma patients harboring favorable mutations regarding the progressive disease (PD) status with appearance of indolent new lesions. METHODS: From June 2010 to October 2012, 102 patients with lung adenocarcinoma, harboring favorable EGFR mutations and treated with EGFR-TKI were analyzed. Definite new lesions were detected during EGFR-TKI therapy, even though the primary target tumors were controlled. RESULTS: Of the 102 patients, 57 continued and 45 discontinued EGFR-TKI therapy. The median overall survival was 529 days for the discontinuation group and 791 days for the continuation group (p = 0.0197). Median survival time after the discontinuation of EGFR-TKI was 181 days and 115 days in the discontinuation and continuation groups, respectively (p = 0.1776), whereas median survival time after the appearance of indolent new lesions was 204 days and 262 days, respectively (p = 0.0237). CONCLUSION: Continuous EGFR-TKI administration in favorable EGFR-mutative lung adenocarcinoma patients with controlled primary tumors did not hinder the survival benefit, despite the appearance of new lesions. PMID- 27372165 TI - Metabolic, autophagic, and mitophagic activities in cancer initiation and progression. AB - Cancer is a complex disease marked by uncontrolled cell growth and invasion. These processes are driven by the accumulation of genetic and epigenetic alterations that promote cancer initiation and progression. Contributing to genome changes are the regulation of oxidative stress and reactive species induced damage to molecules and organelles. Redox regulation, metabolic plasticity, autophagy, and mitophagy play important and interactive roles in cancer hallmarks including sustained proliferation, activated invasion, and replicative immortality. However, the impact of these processes can differ depending on the signaling pathways altered in cancer, tumor type, tumor stage, and/or the differentiation state. Here, we highlight some of the representative studies on the impact of oxidative and nitrosative activities, mitochondrial bioenergetics, metabolism, and autophagy and mitophagy in the context of tumorigenesis. We discuss the implications of these processes for cellular activities in cancer for anti-cancer-based therapeutics. PMID- 27372169 TI - The occlusal imaging and analysis system by T-scan III in tinnitus patients. AB - BACKGROUND: Several studies have demonstrated that the prevalence of temporomandibular disorders (TMDs) in tinnitus patients ranges from 7% to 95%, and it is reported in literature that idiopathic tinnitus patients should be referred to a dentist to define whether or not the tinnitus is associated with TMD. However, the possible pathophysiological relation between TMDs and tinnitus is not generally investigated in clinical practice. METHODS: The patterns and forces of occlusal contacts have been studied by means of T-scan III in 47 tinnitus patients (23 suffering from idiopathic tinnitus and 24 affected by Meniere disease [MD]) and 13 healthy subjects. RESULTS: The center of force target was offset in the opposite direction in 15/23 idiopathic tinnitus and in 7/24 MD patients (p = 0.026). No significant variation was found in the occlusal force. CONCLUSIONS: Our data suggest that a diagnostic screening method for occlusal stability in the intercuspidal position might be clinically useful in idiopathic tinnitus patients. PMID- 27372168 TI - Risk factors of multidrug-resistant Acinetobacter baumannii recurrence after successful eradication in ventilated patients. AB - BACKGROUND: Clinically, multidrug-resistant Acinetobacter baumannii (MDR-AB) recurrence is found in some patients although identified as successfully eradicated. We aim to discover the characteristics of patients with MDR-AB recurrence in the respiratory tract. METHODS: We retrospectively collected 106 chronic respiratory failure patients with MDR-AB harvest in pulmonary secretion culture. RESULTS: MDR-AB was successfully eradicated in 69 patients. Diabetes mellitus (p = 0.030, odds ratio [OR]: 2.7, 95% confidence interval [CI]: 1.1-6.4) and acute respiratory distress syndrome (p = 0.001, OR = 4.8, 95% CI: 1.8-12.7) reduce the MDR-AB eradication rate. Besides, a classification of colonization or infection was made beyond the 69 MDR-AB eradicated patients. In the colonization group, diabetes mellitus (p = 0.009; OR = 5.1, 95% CI: 1.5-17.6) is the only independent factor to increase the recurrence rate. Glycated hemoglobin level is also analyzed for each group to investigate diabetes control effect, but no significant difference found. CONCLUSIONS: Diabetes mellitus is a risk factor of MDR-AB recurrence among MDR-AB-colonized patients; the impact of localized pneumonia patch in MDR-AB-infected patients requires further study to be clarified. PMID- 27372170 TI - A comparison between the effects of propofol-fentanyl with propofol-ketamine for sedation in patients undergoing endoscopic retrograde cholangiopancreatography outside the operating room. AB - BACKGROUND: The efficient and secure techniques of anesthesia and sedation have always been needed for. One of these procedures is endoscopic retrograde cholangiopancreatography (ERCP), due to its painfulness and long duration, has high sensitivity. We compare the effects of propofol-fentanyl (PF) with propofol ketamine (PK) to sedate patients undergoing ERCP. METHODS: In this clinical trial, patients were divided into two groups of 49 people. A group received a pharmaceutical combination of PK, and another group received a pharmaceutical combination of PF. Vital signs of patients, Ramsey Sedation Score, and pain of patients were assessed. The total dosage of used propofol was also recorded. RESULTS: There was no significant difference seen in the patients' hemodynamic characteristics in both groups. Pain at the end of surgery and an hour after it in the PK group was less that was not statistically significant. By Ramsey Sedation Score also significant differences were not seen between groups (p = 0.68). By using total dose of propofol used also a significant difference was not observed between the two groups (p = 0.36). Rate of apnea in PK group was 32% and in the PF group was 63%, which this difference was statistically significant (p < 0.05). CONCLUSION: A comparison between the two drugs combination shows that although in terms of hemodynamic and sedation criteria both groups were similar, but because of the lower amount of pain and apnea in the PK group, this combination may generally in the ERCP procedure is more efficient and safer. PMID- 27372171 TI - Time trend of incidence rates of cleft lip/palate in Taiwan from 1994 to 2013. AB - BACKGROUND: This study was to estimate the incidence rate of cleft lip and/or cleft palate (CL/P) in Taiwan from 1994 to 2013, and to assess the time trend over these years. METHODS: Retrospective data analysis was performed on records of all newborns with CL/P treated at Chang Gung Craniofacial Center, the only treatment center for CL/P in Taiwan, from 1994 to 2013. Three-year moving average rates were computed and linear regression was used to explore the annual average percentage change. RESULTS: From 1994 to 2013, 7282 newborns with CL/P were identified, corresponding to an annual rate of 1.480/00 (95% confidence interval (CI) = 1.450/00-1.520/00). There was a significant decline of rate of cleft lip with or without cleft palate (CL +/- P) (-2.9% +/- 0.2%, p < 0.0001) but slightly increase of rate of cleft palate (CP) only (+0.2% +/- 0.07%, p = 0.004). CONCLUSION: From 1994 to 2013, the annual rate of incidence of CL/P was 1.480/00 in Taiwan. The 2.9% annual decline of the rate was mainly from the CL +/- P group, not the CP group. PMID- 27372172 TI - Esophageal mucormycosis in an immunocompetent child: A rare presentation. AB - Invasive mucormycosis of the esophagus (rare) and gastrointestinal tract is emerging as an important cause of concern in children. It usually affects immunosuppressed individuals. However, infection of immunocompetent children is also seen. The diagnosis of mucormycosis is difficult both at the clinical and the laboratory level, hence leading to unsatisfactory treatment and high mortality rates. The infection is usually life threatening so an early diagnosis and prompt administration of antifungal therapy is imperative. PMID- 27372173 TI - Contraceptive behaviour in North India. PMID- 27372174 TI - Meeting the unmet needs of family planning. PMID- 27372175 TI - Quantifying trabecular bone material anisotropy and orientation using low resolution clinical CT images: A feasibility study. AB - Accounting for spatial variation of trabecular material anisotropy and orientation can improve the accuracy of quantitative computed tomography-based finite element (FE) modeling of bone. The objective of this study was to investigate the feasibility of quantifying trabecular material anisotropy and orientation using clinical computed tomography (CT). Forty four cubic volumes of interest were obtained from micro-CT images of the human radius. Micro-FE modeling was performed on the samples to obtain orthotropic stiffness entries as well as trabecular orientation. Simulated computed tomography images (0.32, 0.37, and 0.5mm isotropic voxel sizes) were created by resampling micro-CT images with added image noise. The gray-level structure tensor was used to derive fabric eigenvalues and eigenvectors in simulated CT images. For 'best case' comparison purposes, Mean Intercept Length was used to define fabric from micro-CT images. Regression was used in combination with eigenvalues, imaged density and FE to inversely derive the constants used in Cowin and Zysset-Curnier fabric-elasticity equations, and for comparing image derived fabric-elasticity stiffness entries to those obtained using micro-FE. Image derived eigenvectors (which indicated trabecular orientation) were then compared to orientation derived using micro-FE. When using clinically available voxel sizes, gray-level structure tensor derived fabric combined with Cowin's equations was able to explain 94-97% of the variance in orthotropic stiffness entries while Zysset-Curnier equations explained 82-88% of the variance in stiffness. Image derived orientation deviated by 4.4-10.8 degrees from micro-FE derived orientation. Our results indicate potential to account for spatial variation of trabecular material anisotropy and orientation in subject-specific finite element modeling of bone using clinically available CT. PMID- 27372176 TI - Genetic and molecular basis of diabetic foot ulcers: Clinical review. AB - Diabetic Foot Ulcers (DFUs) are major complications associated with diabetes and often correlate with peripheral neuropathy, trauma and peripheral vascular disease. It is necessary to understand the molecular and genetic basis of diabetic foot ulcers in order to tailor patient centred care towards particular patient groups. This review aimed to evaluate whether current literature was indicative of an underlying molecular and genetic basis for DFUs and to discuss clinical applications. From a molecular perspective, wound healing is a process that transpires following breach of the skin barrier and is usually mediated by growth factors and cytokines released by specialised cells activated by the immune response, including fibroblasts, endothelial cells, phagocytes, platelets and keratinocytes. Growth factors and cytokines are fundamental in the organisation of the molecular processes involved in making cutaneous wound healing possible. There is a significant role for single nucleotide polymorphism (SNPs) in the fluctuation of these growth factors and cytokines in DFUs. Furthermore, recent evidence suggests a key role for epigenetic mechanisms such as DNA methylation from long standing hyperglycemia and non-coding RNAs in the complex interplay between genes and the environment. Genetic factors and ethnicity can also play a significant role in the development of diabetic neuropathy leading to DFUs. Clinically, interventions which have improved outcomes for people with DFUs or those at risk of DFUs include some systemic therapeutic drug interventions which improve microvascular blood flow, surgical interventions, human growth factors, and hyperbaric oxygen therapy, negative pressure wound therapy, skin replacement or shockwave therapy and the use of topical treatments. Future treatment modalities including stem cell and gene therapies are promising in the therapeutic approach to prevent the progression of chronic diabetic complications. PMID- 27372177 TI - Lacking the 'protective label' of diabetes: Phenytoin-induced distal symmetrical peripheral neuropathy. A clinical case report. AB - This report documents an unusual case of distal symmetrical peripheral neuropathy (DSPN) in an otherwise healthy patient without diabetes mellitus (DM) presenting to a podiatric wound care clinic. The development of gas gangrene coupled with Charcot neuroarthropathic changes ultimately resulted in a potentially life saving transmetatarsal (TMT) amputation. Causation of, or at least a contributor to, the DSPN was likely phenytoin usage for epileptic seizures. Long-term use of phenytoin can lead to axonal shrinkage and random clusters of nerve demyelination [1]. Clinical standards for DM-induced DSPN indicate that annual comprehensive neurological assessment to detect nerve function deterioration is warranted [2]. This can aid in identifying patients at high risk of diabetic foot ulceration. However, oftentimes, patients exhibiting medication-induced neuropathy are not assessed to determine severity of the neuropathy nor are they educated about ulcer prevention in the same manner as patients with DM. This report advocates for a standardized threshold of diagnostic and preventative investigation for neuropathy of all aetiologies; diabetic, traumatic, viral, medication-induced and idiopathic. PMID- 27372178 TI - Trichilemmoma in Childhood. PMID- 27372179 TI - Defence sugarcane glycoproteins disorganize microtubules and prevent nuclear polarization and germination of Sporisorium scitamineum teliospores. AB - Microtubules (MTs) are involved in the germination of Sporisorium scitamineum teliospores. Resistant varieties of sugar cane plants produce defence glycoproteins that prevent the infection of the plants by the filamentous fungi Sporisorium scitamineum. Here, we show that a fraction of these glycoproteins prevents the correct arrangement of MTs and causes nuclear fragmentation defects. As a result, nuclei cannot correctly migrate through the growing hyphae, causing germinative failure. Arginase activity contained in defence glycoproteins is already described for preventing fungal germination. Now, its enzymatically active form is presented as a link between the defensive capacity of glycoproteins and the MT disorganization in fungal cells. Active arginase is produced in healthy and resistant plants; conversely, it is not detected in the juice from susceptible varieties, which explains why MT depolarization, nuclear disorganization as well as germination of teliospores are not significantly affected by glycoproteins from non-resistant plants. Our results also suggest that susceptible plants try to increase their levels of arginase after detecting the presence of the pathogen. However, this signal comes "too late" and such defensive mechanism fails. PMID- 27372180 TI - Isolation and characterization of Nylanderia fulva virus 1, a positive-sense, single-stranded RNA virus infecting the tawny crazy ant, Nylanderia fulva. AB - We report the discovery of Nylanderia fulva virus 1 (NfV-1), the first virus identified and characterized from the ant, Nylanderia fulva. The NfV-1 genome (GenBank accession KX024775) is 10,881 nucleotides in length, encoding one large open reading frame (ORF). Helicase, protease, RNA-dependent RNA polymerase, and jelly-roll capsid protein domains were recognized within the polyprotein. Phylogenetic analysis placed NfV-1 in an unclassified clade of viruses. Electron microscopic examination of negatively stained samples revealed particles with icosahedral symmetry with a diameter of 28.7+/-1.1nm. The virus was detected by RT-PCR in larval, pupal, worker and queen developmental stages. However, the replicative strand of NfV-1 was only detected in larvae. Vertical transmission did not appear to occur, but horizontal transmission was facile. The inter colonial field prevalence of NfV-1 was 52+/-35% with some local infections reaching 100%. NfV-1 was not detected in limited samples of other Nylanderia species or closely related ant species. PMID- 27372182 TI - [Primary hyperoxaluria: A review]. AB - Primary hyperoxalurias (PH) are inborn errors in the metabolism of glyoxalate and oxalate with recessive autosomal transmission. As a result, an increased endogenous production of oxalate leads to exessive urinary oxalate excretion. PH type 1, the most common form, is due to a deficiency of the peroxisomal enzyme alanine: Glyoxylate aminotransferase (AGT) in the liver. PH type 2 is due to the deficiency of the glyoxylate reductase/hydroxypyruvate reductase, present in the cytosol of hepatocytes and leucocytes. PH type 3 is linked to the gene HOGA1, encoding a mitochondrial enzyme, the 4-hydroxy-2-oxo-glutarate aldolase. Recurrent urolithiaisis and nephrocalcinosis are the markers of the disease. As a result, a progressive dysfunction of the kidneys is commonly observed. At the stage of severe chronic kidney disease, plasma oxalate increase leads to a systemic oxalosis. Diagnostic is often delayed and it based on stone analysis, cristalluria, oxaluria determination and DNA analysis. Early initiation of conservative treatment including high fluid intake and long-term co administration of inhibitors of calcium oxalate crystallization and pyridoxine, could efficiently prevent end stage renal disease. In end stage renal failure, a combined liver-kidney transplantation corrects the enzyme defect. PMID- 27372183 TI - Beneficial effects of rapid introduction of adaptive servo-ventilation in the emergency room in patients with acute cardiogenic pulmonary edema. AB - BACKGROUND: Adaptive servo-ventilation (ASV) at home has been used for patients with chronic heart failure. However, its effect on acute cardiogenic pulmonary edema (ACPE) is not clear. The aim of this study was to elucidate the effect of ASV use in the emergency room in patients with ACPE. METHODS: We enrolled 198 consecutive patients with ACPE. Eighty patients received standard therapies, such as oxygen inhalation and vasodilators (conventional therapy group), and 118 received ASV in addition to standard therapy (ASV therapy group). ASV was initiated in the emergency room immediately after diagnosis. The procedure was switched over from ASV to endotracheal intubation (ETI) when oxygenation was insufficient. RESULTS: The ETI rate in the ASV therapy group was significantly lower than that in the conventional therapy group (3% vs. 21%, p<0.01). The intensive care unit and/or high care unit length of stay in the ASV therapy group was also significantly shorter than that in the conventional therapy group (1.9+/ 2.1 days vs. 5.3+/-6.8 days, p<0.01). Consequently, the hospitalization period in the ASV therapy group was shorter than that in the conventional therapy group (19.3+/-11.0 days vs. 26.3+/-16.6 days, p<0.01). CONCLUSION: In patients with ACPE, rapid introduction of ASV in the emergency room reduces the need for ETI and decreases the hospitalization period. PMID- 27372181 TI - Contributions of P2- and P22-like prophages to understanding the enormous diversity and abundance of tailed bacteriophages. AB - We identified 9371 tailed phage prophages of 20 known types in reported complete genome sequences of 3298 bacteria in the Salmonella genus. These include 4758 P2 type and 744 P22 type prophages. The latter prophage types were found in the genome sequences of 127 and 24 bacterial host genera, increasing the known host ranges of phages in these groups by 114 and 20 genera, respectively. These prophage nucleotide sequences displayed much more diversity than was previously known from the 48 P2 and 24 P22 type authentic phages whose genomes have been sequenced. More detailed analysis of these prophage sequences indicated that major capsid protein (MCP) gene exchange between tailed phage clusters or types is extremely rare and that P22 prophage-encoded tailspikes correspond perfectly with their hosts' surface polysaccharide structure; thus, MCP and tailspike sequences accurately predict tailed phage type (and thus lifestyle) and host cell surface polysaccharide structure, respectively. PMID- 27372184 TI - Efficacy of Prophylactic Antibiotics in Simple Knee Arthroscopy. AB - PURPOSE: To determine the association between the use of preoperative antibiotics and the risk of postoperative infection after simple knee arthroscopy. METHODS: The electronic medical records of a large integrated health care organization were used to identify patients who underwent simple knee arthroscopy between 2007 and 2012. Patient demographics, potential infection risk factors, and antibiotic administration data were extracted. Simple knee arthroscopy included debridement, meniscectomy, meniscus repair, synovectomy, microfracture, and lateral release. Complex knee arthroscopy, septic knees, and cases involving fractures were excluded. Deep infection was defined as a positive synovial fluid culture or signs and symptoms of infection and gross pus in the knee. Superficial infection was defined as clinical signs of infection localized to a portal site and treatment with an antibiotic. RESULTS: Of 40,810 simple knee arthroscopies, 32,836 (80.5%) received preoperative antibiotics and 7,974 (19.5%) did not. There were 25 deep infections in the antibiotic group (0.08%) and 11 in the no antibiotics group (0.14%) (risk ratio = 0.55, 95% confidence interval: 0.27 to 1.12, P = .10). There were 134 superficial infections in the antibiotic group (0.41%) and 32 in the no-antibiotics group (0.40%) (risk ratio = 1.01, 95% confidence interval: 0.29 to 1.49, P = .93). CONCLUSIONS: In our large sample of patients who underwent simple knee arthroscopy, there was no association between preoperative antibiotic use and postoperative deep or superficial infection rates at the 95% confidence level (P = .05). There was an association between preoperative antibiotic use and a decreased deep infection rate at the P = .10 level. LEVEL OF EVIDENCE: Level IV, case series. PMID- 27372185 TI - Identification of microRNAs in rice root in response to nitrate and ammonium. AB - Nitrate and ammonium are two major nitrogen (N) sources for higher plants, but they differ in utilization and signaling. MicroRNAs (miRNAs) play an essential role in N signal transduction; however, knowledge remains limited about the regulatory role of miRNAs responsive to different N sources, especially in crop plants. To get global overview on miRNAs involved in N response in rice, we performed high-throughput small RNA-sequencing under different nitrate and ammonium treatments. The results demonstrated that only 16 and 11 miRNAs were significantly induced by nitrate and ammonium under short-term treatment, respectively. However, 60 differentially expressed miRNAs were found between nitrate and ammonium under long-term cultivation. These results suggested that miRNA response greatly differentiates between nitrate and ammonium treatments. Furthermore, 44 miRNAs were found to be differentially expressed between high- and low-N conditions. Our study reveals comprehensive expression profiling of miRNAs responsive to different N sources and different N treatments, which advances our understanding on the regulation of different N signaling and homeostasis mediated by miRNAs. PMID- 27372186 TI - 3-Substituted-4-hydroxycoumarin as a new scaffold with potent CDK inhibition and promising anticancer effect: Synthesis, molecular modeling and QSAR studies. AB - A new series of 3-substituted-4-hydroxycoumarin derivatives was designed, synthesized, and evaluated for CDK inhibiting and anticancer activities. All the synthesized target compounds showed remarkably high affinity and selectivity towards CDK1B, compared to flavopiridol, with Ki values in the low nanomolar range (Ki=0.35-0.88nM). Most of them elicited considerable inhibiting effect against CDK9T1 (Ki=3.26-23.45nM). Moreover, all the target compounds were tested in vitro against eighteen types of human tumor cell lines. The hydrazone 3a, N phenylpyrazoline derivative 6b and 2-aminopyridyl-3-carbonitrile derivative 8c were the most potent anticancer agents against MCF-7 breast cancer cell line (IC50=0.21, 0.21 and 0.23nM, respectively). The target compounds 3a, 6b and 8c were further evaluated in MCF-7 breast cancer mouse xenograft model and showed in vivo efficacy at 10mg/kg dose. The docking study confirmed a unique binding mode in the active site of CDK1B with better score than flavopiridol. Quantitative structure activity relationship study was done and revealed a highly predictive power R(2) of 0.81. PMID- 27372187 TI - A combination of three-dimensional printing and computer-assisted virtual surgical procedure for preoperative planning of acetabular fracture reduction. AB - OBJECTIVE: Treatment of acetabular fractures remains one of the most challenging tasks that orthopaedic surgeons face. An accurate assessment of the injuries and preoperative planning are essential for an excellent reduction. The purpose of this study was to evaluate the feasibility, accuracy and effectiveness of performing 3D printing technology and computer-assisted virtual surgical procedures for preoperative planning in acetabular fractures. We hypothesised that more accurate preoperative planning using 3D printing models will reduce the operation time and significantly improve the outcome of acetabular fracture repair. METHODS: Ten patients with acetabular fractures were recruited prospectively and examined by CT scanning. A 3-D model of each acetabular fracture was reconstructed with MIMICS14.0 software from the DICOM file of the CT data. Bone fragments were moved and rotated to simulate fracture reduction and restore the pelvic integrity with virtual fixation. The computer-assisted 3D image of the reduced acetabula was printed for surgery simulation and plate pre bending. The postoperative CT scan was performed to compare the consistency of the preoperative planning with the surgical implants by 3D-superimposition in MIMICS14.0, and evaluated by Matta's method. RESULTS: Computer-based pre operations were precisely mimicked and consistent with the actual operations in all cases. The pre-bent fixation plates had an anatomical shape specifically fit to the individual pelvis without further bending or adjustment at the time of surgery and fracture reductions were significantly improved. Seven out of 10 patients had a displacement of fracture reduction of less than 1mm; 3 cases had a displacement of fracture reduction between 1 and 2mm. CONCLUSIONS: The 3D printing technology combined with virtual surgery for acetabular fractures is feasible, accurate, and effective leading to improved patient-specific preoperative planning and outcome of real surgery. The results provide useful technical tips in planning pelvic surgeries. PMID- 27372188 TI - Covered Stent for Large Coronary Arterial Fistula and Adjacent Atherosclerotic Plaque With Stenosis in a Patient With Non-ST-Segment Elevation Myocardial Infarction. PMID- 27372189 TI - Right Coronary Artery With Anomalous Origin: The Role of Imaging Techniques. PMID- 27372191 TI - Unraveling a Knot in the Heart: Tackling an Unanticipated Complication. PMID- 27372190 TI - The Impact of Timing of Ischemic and Hemorrhagic Events on Mortality After Percutaneous Coronary Intervention: The ADAPT-DES Study. AB - OBJECTIVES: The aim of this study was to understand the impact of the timing of ischemic and hemorrhagic events after percutaneous coronary intervention (PCI) with drug-eluting stents on subsequent mortality. BACKGROUND: These events have been strongly associated with subsequent death. METHODS: In the multicenter, prospective ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug Eluting Stents) study, patients at 11 clinical sites with successful PCI with drug eluting stents underwent assessment of platelet function and were followed for 2 years. Events occurring after PCI-definite or probable stent thrombosis (ST), myocardial infarction (MI) not related to ST, and clinically relevant bleeding (CB)-were classified as early (<=30 days), late (31 to 365 days), or very late (>365 days). Mortality within 30 days of each event was estimated by Kaplan-Meier methodology. Cox regression multivariate modeling was used to analyze the relationship between each event (as a time-updated variable) and mortality over the entire study period. RESULTS: Among 8,582 patients, 1,060 (12.4%) had events 691 (8.1%) had CB, 294 (3.4%) had MI, and 75 (0.9%) had ST-and 7,522 (87.6%) had no events. The highest risk was associated with early ST (38.5% mortality at 30 days after the event), whereas very late MI (7.5%) and late CB (7.3%) were less dangerous. By multivariate analysis, each event was independently predictive of death, with hazard ratios of 2.4, 1.8, and 11.4, respectively (p < 0.0001). CONCLUSIONS: Approximately 1 in 8 patients successfully undergoing PCI with drug eluting stents had CB, MI, or ST during the ensuing 2 years. These events are associated with an increased hazard of mortality, particularly within the first 30 days following the event, warranting efforts to prevent their occurrence. PMID- 27372192 TI - High-Risk Transcatheter Aortic Valve Replacement With Evolut-R CoreValve to Simultaneously Treat Severe Calcific Aortic Stenosis and a Large Aortic Root Pseudoaneurysm. PMID- 27372193 TI - Why Radial Access Is Better. PMID- 27372194 TI - Adapting DAPT to Improve Outcomes After Coronary Stenting. PMID- 27372195 TI - Radial Versus Femoral Access for Coronary Interventions Across the Entire Spectrum of Patients With Coronary Artery Disease: A Meta-Analysis of Randomized Trials. AB - OBJECTIVES: The aim of this study was to provide a quantitative appraisal of the effects on clinical outcomes of radial access for coronary interventions in patients with coronary artery disease (CAD). BACKGROUND: Randomized trials investigating radial versus femoral access for percutaneous coronary interventions have provided conflicting evidence. No comprehensive quantitative appraisal of the risks and benefits of each approach is available across the whole spectrum of patients with stable or unstable CAD. METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for randomized trials comparing radial versus femoral access for coronary interventions. Data were pooled by meta-analysis using a fixed-effects or a random-effects model, as appropriate. Pre-specified subgroup analyses according to clinical presentation, in terms of stable CAD, non-ST segment elevation acute coronary syndromes, or ST-segment elevation myocardial infarction were performed. RESULTS: Twenty-four studies enrolling 22,843 participants were included. Compared with femoral access, radial access was associated with a significantly lower risk for all-cause mortality (odds ratio [OR]: 0.71; 95% confidence interval [CI]: 0.59 to 0.87; p = 0.001, number needed to treat to benefit [NNTB] = 160), major adverse cardiovascular events (OR: 0.84; 95% CI: 0.75 to 0.94; p = 0.002; NNTB = 99), major bleeding (OR: 0.53; 95% CI: 0.42 to 0.65; p < 0.001; NNTB = 103), and major vascular complications (OR: 0.23; 95% CI: 0.16 to 0.35; p < 0.001; NNTB = 117). The rates of myocardial infarction or stroke were similar in the 2 groups. Effects of radial access were consistent across the whole spectrum of patients with CAD for all appraised endpoints. CONCLUSIONS: Compared with femoral access, radial access reduces mortality and MACE and improves safety, with reductions in major bleeding and vascular complications across the whole spectrum of patients with CAD. PMID- 27372196 TI - Stuck Leaflet After Transcatheter Aortic Valve Replacement With a SAPIEN-3 Valve: New Valve, Old Complication. PMID- 27372197 TI - Borrelia burgdorferi sensu lato in Ixodes cf. neuquenensis and Ixodes sigelos ticks from the Patagonian region of Argentina. AB - This study was conducted to detect Borrelia burgdorferi sensu lato infection in ixodid ticks from the Patagonia region in the south of Argentina. Therefore, ticks were collected on rodents in the provinces of Chubut, Rio Negro and Santa Cruz. These ticks were identified as nymphs of Ixodes cf. neuquenensis and Ixodes sigelos. The B. burgdorferi s.l. infection was tested by a battery of PCR methods targeting the gene flagellin (fla) and the rrfA-rrlB intergenic spacer region (IGS). Three pools of I. sigelos nymphs from Chubut and Santa Cruz provinces as well as one pool of I. cf. neuquenensis nymphs from Rio Negro province were tested positive in the fla-PCR. The samples of I. sigelos were also positive for the IGS-PCR. Phylogenetically, the haplotypes found in the positive ticks belong to the B. burgdorferi s.l. complex, and they were closely related to Borrelia chilensis, a genospecies isolated from Ixodes stilesi in Chile. The pathogenic relevance of the Borrelia genospecies detected in both I. neuquenensis and I. sigelos is unknown. PMID- 27372198 TI - Challenges facing an understanding of the nature of low-energy excited states in photosynthesis. AB - While the majority of the photochemical states and pathways related to the biological capture of solar energy are now well understood and provide paradigms for artificial device design, additional low-energy states have been discovered in many systems with obscure origins and significance. However, as low-energy states are naively expected to be critical to function, these observations pose important challenges. A review of known properties of low energy states covering eight photochemical systems, and options for their interpretation, are presented. A concerted experimental and theoretical research strategy is suggested and outlined, this being aimed at providing a fully comprehensive understanding. PMID- 27372199 TI - Hepatocellular carcinoma: Exploring the impact of ethnicity on molecular biology. AB - Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third leading cause of cancer-related death. The high rate of diagnosis in non-curable stages and the lack of novel active treatments make it necessary to review all the possible sources of misleading results in this scenario. The incidence of HCC shows clear geographical variation with higher annual incidence in Asia and Africa than in Western countries; we aimed to review the literature to find if there are different trends in the main activated molecular pathways. Hyperactivation of RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signalling and epithelial to mesenchymal transition (EMT) process are more prevalent in the Western population; however, fibroblast growth factor (FGF), transforming growth factor beta (TGFbeta) and Notch pathways seems to be more relevant in Asian population. Whether these variations just reflect the distinct distribution of known causes of HCC or proper ethnical differences remain to be elucidated. Nevertheless, these clearly different patterns are relevant to regional or worldwide clinical trial design. If this information is neglected by sponsors and researchers the rate of failure in HCC trials will not improve. PMID- 27372200 TI - Immunotherapy advances in uro-genital malignancies. AB - Immunotherapy for the treatment of cancer has made significant progresses over the last 20 years. Multiple efforts have been attempted to restore immune mediated tumor elimination, leading to the development of several targeted immunotherapies. Data from recent clinical trials suggest that these agents might improve the prognosis of patients with advanced genito-urinary (GU) malignancies. Nivolumab has been the first immune checkpoint-inhibitor approved for pre-treated patients with metastatic renal cell carcinoma. Pembrolizumab and atezolizumab have shown promising results in both phase I and II trials in urothelial carcinoma. Brentuximab vedotin has demonstrated early signals of clinical activity and immunomodulatory effects in highly pre-treated patients with testicular germ cell tumors. In this review, we have summarized the major clinical achievements of immunotherapy in GU cancers, focusing on immune checkpoint blockade as well as the new immunomodulatory monoclonal antibodies (mAbs) under clinical evaluation for these malignancies. PMID- 27372201 TI - Congenital philtral fistula revealing epidermoid cyst: An unusual case. PMID- 27372203 TI - Growth hormone positive effects on craniofacial complex in Turner syndrome. AB - OBJECTIVE: Turner syndrome occurs in phenotypic females with complete or partial absence of X chromosome. The leading symptom is short stature, while numerous but mild stigmata manifest in the craniofacial region. These patients are commonly treated with growth hormone to improve their final height. The aim of this study was to assess the influence of long-term growth hormone therapy on craniofacial morphology in Turner syndrome patients. DESIGN: In this cross-sectional study cephalometric analysis was performed on 13 lateral cephalograms of patients with 45,X karyotype and the average age of 17.3 years, who have received growth hormone for at least two years. The control group consisted of 13 Turner syndrome patients naive to growth hormone treatment, matched to study group by age and karyotype. Sixteen linear and angular measurements were obtained from standard lateral cephalograms. Standard deviation scores were calculated in order to evaluate influence of growth hormone therapy on craniofacial components. RESULTS: In Turner syndrome patients treated with growth hormone most of linear measurements were significantly larger compared to untreated patients. Growth hormone therapy mainly influenced posterior face height, mandibular ramus height, total mandibular length, anterior face height and maxillary length. While the increase in linear measurements was evident, angular measurements and facial height ratio did not show statistically significant difference. Acromegalic features were not found. CONCLUSIONS: Long-term growth hormone therapy has positive influence on craniofacial development in Turner syndrome patients, with the greatest impact on posterior facial height and mandibular ramus. However, it could not compensate X chromosome deficiency and normalize craniofacial features. PMID- 27372202 TI - Tongue implant for assistive technologies: Test of migration, tissue reactivity and impact on tongue function. AB - OBJECTIVE: The Tongue Drive System (TDS) is a new wearable assistive technology (AT), developed to translate voluntary tongue movements to user-defined computer commands by tracking the position of a titanium-encased magnetic tracer (Ti-Mag) implanted into the tongue. TDS application, however, is constrained by limited information on biological consequence and safety of device implantation into the tongue body. Here we implant a stainless-steel pellet in the rat tongue and assay pellet migration, tongue lick function, and tongue histology to test the safety and biocompatibility of unanchored tongue implants. DESIGN: Water consumption, weight and lick behavior were measured before and for >24days after implantation of a stainless-steel spherical pellet (0.5mm) into the anterior tongue body of twelve adult male rats. X-rays were obtained weekly to assess pellet migration. Pellet location and tissue reaction to implantation were determined by post mortem dissection and histology of the anterior tongue. RESULTS: By dissection pellets were distributed across the transverse plane of the tongue. Measures of water consumption, weight, and lick behavior were unchanged by implantation except for a decrease in consumption immediately post-implantation in some animals. By X-ray, there was no migration of the implant, a finding supported by pellet encapsulation demonstrated histologically. Measures of lick behavior were minimally impacted by implantation. CONCLUSION: A smooth spherical stainless steel implant in the anterior tongue of the rat does not migrate, is encapsulated and does not substantially impact lick behavior. These findings support the implantation of small tracers in the anterior tongue in humans for operating wearable assistive technologies. PMID- 27372204 TI - Different 57Fe microenvironments in the nanosized iron cores in human liver ferritin and its pharmaceutical analogues on the basis of temperature dependent Mossbauer spectroscopy. AB - Mossbauer spectra of human liver ferritin and its pharmaceutical analogues Ferrum Lek and Maltofer(r) measured at various temperatures within the range of 295-83K were fitted using five quadrupole doublets related to different 57Fe microenvironments in various layers/regions of the ferrihydrite and akaganeite iron cores. The observed anomalous temperature dependences of some Mossbauer parameters were considered as a result of low temperature structural rearrangements in different layers/regions in the iron core. PMID- 27372205 TI - Basal testosterone, leadership and dominance: A field study and meta-analysis. AB - This article examines the role of basal testosterone as a potential biological marker of leadership and hierarchy in the workplace. First, we report the result of a study with a sample of male employees from different corporate organizations in the Netherlands (n=125). Results showed that employees with higher basal testosterone levels reported a more authoritarian leadership style, but this relationship was absent among those who currently held a real management position (i.e., they had at least one subordinate). Furthermore, basal testosterone levels were not different between managers and non-managers, and testosterone was not associated with various indicators of status and hierarchy such as number of subordinates, income, and position in the organizational hierarchy. In our meta analysis (second study), we showed that basal testosterone levels were not associated with leadership in men nor in women (9 studies, n=1103). Taken together, our findings show that basal testosterone is not associated with having a leadership position in the corporate world or related to leadership styles in leaders. We suggest that basal testosterone could play a role in acquiring leadership positions through dominant and authoritarian behavior. PMID- 27372206 TI - Impact of adipose tissue composition on cardiovascular risk assessment in patients with stable coronary artery disease. AB - BACKGROUND AND AIMS: Visceral adipose tissue (VAT), unlike subcutaneous adipose tissue (SAT), is highly correlated with cardiovascular risk factors. This study aimed to evaluate the predictive value of adipose tissue composition, as measured by computed tomography, for cardiovascular events in patients with stable coronary artery disease. METHODS: 357 consecutive patients who underwent 64-slice computed tomography and elective percutaneous coronary intervention (PCI) were recruited. The ratio of visceral to subcutaneous adipose tissue (VAT/SAT) was calculated. Patients were divided into three groups in accordance with VAT/SAT (low VAT/SAT, <0.55 [<25th percentile]; moderate VAT/SAT, 0.55-1.03 [25th-75th percentile]; high VAT/SAT, >=1.03 [>=75th percentile]). The investigated risk factors were hypertension, hyperglycaemia, and dyslipidaemia. We analysed the incidence of major adverse cardiovascular events (MACE), defined as the composite of cardiac death, myocardial infarction, and any revascularization. RESULTS: The rate of patients with two or more concomitant risk factors was significantly higher in the high VAT/SAT group (p = 0.006). During 1480 person-years, 109 events were documented. There was a significant association between the incidence of MACE and VAT/SAT, with the worst event-free survival rate in the high VAT/SAT group (log-rank, p = 0.01). In Cox analysis, the hazard ratio of high VAT/SAT for MACE was 2.72 (95% confidence interval 1.04-7.09, p = 0.04) compared with the low VAT/SAT after adjustment for confounding factors. CONCLUSIONS: Increased VAT/SAT is independently associated with the incidence of MACE, indicating that adipose tissue composition is a useful predictor of cardiovascular outcome, after elective PCI. PMID- 27372208 TI - Clinician prediction of survival versus the Palliative Prognostic Score: Which approach is more accurate? AB - BACKGROUND: Clinician prediction of survival (CPS) has low accuracy in the advanced cancer setting, raising the need for prediction models such as the palliative prognostic (PaP) score that includes a transformed CPS (PaP-CPS) and five clinical/laboratory variables (PaP-without CPS). However, it is unclear if the PaP score is more accurate than PaP-CPS, and whether PaP-CPS helps to improve the accuracy of PaP score. We compared the accuracy among PaP-CPS, PaP-without CPS and PaP-total score in patients with advanced cancer. PATIENTS AND METHODS: In this prospective study, PaP score was documented in hospitalised patients seen by palliative care. We compared the discrimination of PaP-CPS versus PaP-total and PaP-without CPS versus PaP-total using four indices: concordance statistics, area under the receiver-operating characteristics curve (AUC), net reclassification index and integrated discrimination improvement for 30-day survival and 100-day survival. RESULTS: A total of 216 patients were enrolled with a median survival of 109 d (95% confidence interval [CI] 71-133 d). The AUC for 30-day survival was 0.57 (95% CI 0.47-0.67) for PaP-CPS, 0.78 (95% CI 0.7 0.87) for PaP-without CPS, and 0.73 (95% CI 0.64-0.82) for PaP-total score. PaP total was significantly more accurate than PaP-CPS according to all four indices for both 30-day and 100-day survival (P < 0.001). PaP-without CPS was significantly more accurate than PaP-total for 30-day survival (P < 0.05). CONCLUSION: We found that PaP score was more accurate than CPS, and the addition of CPS to the prognostic model reduced its accuracy. This study highlights the limitations of clinical gestalt and the need to use objective prognostic factors and models for survival prediction. PMID- 27372209 TI - Understanding the 'Silver Book' - An important reference for standardised nomenclature in clinical laboratory sciences. AB - Clinical laboratories perform a wide menu of testing (examinations). Successful requesting, examination, and ordering in this environment requires clear standardised nomenclature. The Silver Book (SB) is an IUPAC (International Union of Pure and Applied Chemistry) publication, produced with the support of both IUPAC and the IFCC (International Federation of Clinical Chemistry and Laboratory Medicine), that makes recommendations on logical standardised nomenclature, symbols, properties, and units in many disciplines of the clinical laboratory sciences. These recommendations are founded on and in agreement with the principles and work of the International Organization for Standardization (ISO), Bureau International des Poids et Mesures (BIPM), IUPAC, and the IFCC. Practical applications described are based on those scientific principles. The SB recommendations apply to all types of examination, not only to measurement of quantities but also examination of nominal properties where no magnitude is involved. The SB is applicable not only to clinical chemistry, but to many other clinical laboratory disciplines. For examples, reports regarding haemostasis, toxicology, clinical microbiology, reproduction and fertility, clinical pharmacology, clinical allergology, clinical molecular biology, and clinical immunohaematology have been published by the IUPAC and the IFCC. Peak scientific bodies such as the IUPAC and the IFCC have important roles in the development of sound international standards for nomenclature of examinations. Such standards support safe and effective representation of patient health information, foster portability, and empower future decision support systems. PMID- 27372207 TI - Quantifying the effect of side branches in endothelial shear stress estimates. AB - BACKGROUND AND AIMS: Low and high endothelial shear stress (ESS) is associated with coronary atherosclerosis progression and high-risk plaque features. Coronary ESS is currently assessed via computational fluid dynamic (CFD) simulation of coronary blood flow in the lumen geometry determined from invasive imaging such as intravascular ultrasound and optical coherence tomography. This process typically omits side branches of the target vessel in the CFD model as invasive imaging of those vessels is not usually clinically-indicated. The purpose of this study was to determine the extent to which this simplification affects the determination of those regions of the coronary endothelium subjected to pathologic ESS. METHODS: We determined the diagnostic accuracy of ESS profiling without side branches to detect pathologic ESS in the major coronary arteries of 5 hearts imaged ex vivo with computed tomography angiography (CTA). ESS of the three major coronary arteries was calculated both without (test model), and with (reference model) inclusion of all side branches >1.5 mm in diameter, using previously-validated CFD approaches. Diagnostic test characteristics (accuracy, sensitivity, specificity and negative and positive predictive value [NPV/PPV]) with respect to the reference model were assessed for both the entire length as well as only the proximal portion of each major coronary artery, where the majority of high-risk plaques occur. RESULTS: Using the model without side branches overall accuracy, sensitivity, specificity, NPV and PPV were 83.4%, 54.0%, 96%, 95.9% and 55.1%, respectively to detect low ESS, and 87.0%, 67.7%, 90.7%, 93.7% and 57.5%, respectively to detect high ESS. When considering only the proximal arteries, test characteristics differed for low and high ESS, with low sensitivity (67.7%) and high specificity (90.7%) to detect low ESS, and low sensitivity (44.7%) and high specificity (95.5%) to detect high ESS. CONCLUSIONS: The exclusion of side branches in ESS vascular profiling studies greatly reduces the ability to detect regions of the major coronary arteries subjected to pathologic ESS. Single-conduit models can in general only be used to rule out pathologic ESS. PMID- 27372210 TI - A sensitive LC-MS/MS method for the quantification of urinary 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) including pediatric reference interval. AB - BACKGROUND: Oxidative stress has been implicated in numerous diseases, including arthritis, atherosclerosis, Alzheimer's disease, cancer, diabetes, hypertension, and inflammation. 8-iso-prostaglandin F2alpha, a member of the F2 isoprostane family, has been well-accepted as a valuable biomarker for the assessment of oxidative stress. METHODS: We report the development and validation of an ultra sensitive LC-MS/MS assay for urinary 8-iso-PGF2alpha measurements in pediatric population. RESULTS: The assay was linear from 0.024 to 20nmol/l (R(2)=0.99). Recoveries were above 85% and matrix effects were below 5%. The variability was determined at nmol/l concentration: the intra-day variability (%CV) ranged from 3.9% to 4.5% (n=20); and the inter-day variability ranged from 4.3% to 5.7% (n=20). The accuracy of our laboratory developed test was evaluated with a clinical reference laboratory (n=39), and a correlation coefficient of 0.9257 was observed. Reference interval were established to be <0.5ng/mg creatinine in a group of pediatric population (2months-18years, n=123). CONCLUSIONS: The precision of the assay will allow for accurate assessment of oxidative stress, and is acceptable for patient testing, particularly in pediatric population. PMID- 27372211 TI - Asymmetric gradient coil design for use in a short, open bore magnetic resonance imaging scanner. AB - A conventional cylindrical whole-body MRI scanner has a long bore that may cause claustrophobia for some patients in addition to being inconvenient for healthcare workers accessing the patient. A short-bore scanner usually offers a small sized imaging area, which is impractical for imaging some body parts, such as the torso. This work proposes a novel asymmetric gradient coil design that offers a full-sized imaging area close to one end of the coil. In the new design, the primary and shielding coils are connected at one end whilst separated at the other, allowing the installation of the cooling system and shim trays. The proposed coils have a larger wire gap, higher efficiency, lower inductance, less resistance and a higher figure of merit than the non-connected coils. This half connected coil structure not only improves the coils' electromagnetic performance, but also slightly attenuates acoustic radiation at most frequencies when compared to a non-connected gradient coil. It is also quieter in some frequency bands than a conventional symmetric gradient coil. PMID- 27372212 TI - Arterial spin-labeled perfusion for vascular anomalies in the pediatric head and neck. AB - OBJECTIVE: To study the arterial spin-labeled (ASL) imaging features of vascular anomalies in the head and neck. MATERIALS AND METHODS: The presence or absence of ASL signal was evaluated for each vascular anomaly, and a comparison with conventional magnetic resonance (MR) sequences was performed. RESULTS: Twenty five children were identified with vascular anomalies. All proliferating infantile hemangiomas demonstrated hyperintense ASL signal. There were eight cases that ASL imaging provided additional information when compared with conventional MR sequences, including increased lesion conspicuity and altered perfusion. CONCLUSIONS: ASL imaging of cutaneous vascular anomalies shows specific signal intensity patterns and can provide additional value when compared to conventional MR sequences. PMID- 27372214 TI - The European Histamine Research Society 45th Annual Meeting, May 11-14, 2016 Florence, Italy. PMID- 27372213 TI - Comparison of Healthcare Workers Transferring Patients Using Either Conventional Or Robotic Wheelchairs: Kinematic, Electromyographic, and Electrocardiographic Analyses. AB - Objectives. The aim of this study was to compare the musculoskeletal and physical strain on healthcare workers, by measuring range of motion (ROM), muscle activity, and heart rate (HR), during transfer of a simulated patient using either a robotic wheelchair (RWC) or a conventional wheelchair (CWC). Methods. The subjects were 10 females who had work experience in transferring patients and another female adult as the simulated patient to be transferred from bed to a RWC or a CWC. In both experimental conditions, ROM, muscle activity, and HR were assessed in the subjects using motion sensors, electromyography, and electrocardiograms. Results. Peak ROM of shoulder flexion during assistive transfer with the RWC was significantly lower than that with the CWC. Values for back muscle activity during transfer were lower with the RWC than with the CWC. Conclusions. The findings suggest that the RWC may decrease workplace injuries and lower back pain in healthcare workers. PMID- 27372215 TI - Impulse Control Disorders in Parkinson's Disease are Associated with Alterations in Reward-Related Cortical Oscillations. AB - BACKGROUND: Impulse control disorders (ICDs) in Parkinson's disease (PD) are related to treatment with dopamine agonists, which is thought to deregulate the dopaminergic mesolimbic pathway and impair reward evaluation. EEG studies in healthy controls (HCs) have suggested that the increase in theta power observed after negative outcome is a marker of reward processing. OBJECTIVE: To compare outcome-locked, event-related spectral perturbation in a gambling task in PD patients with and without ICDs and in HCs. METHODS: Twelve PD patients with ICDs, 12 PD patients without ICDs and 14 HCs underwent EEG while performing a gambling task. The groups were compared in terms of (i) the peak EEG power in the theta (4 7 Hz), alpha (8-14 Hz) and beta (15-30 Hz) frequency bands between 200 and 500 ms after the outcome, and (ii) time-frequency plots at Fz, FCz and Cz. RESULTS: Positive outcomes were associated with greater theta power than negative outcomes in patients without ICDs and in HCs, but not in patients with ICDs. Patients with ICDs and HCs displayed greater theta power following unexpectedly high outcomes. HCs displayed greater beta power following high amplitude than low amplitude outcomes, whereas patients with ICD showed the opposite pattern. CONCLUSIONS: In PD, ICDs are associated with (i) weaker modulation of frontocentral theta power by reward valence, (ii) greater frontocentral theta power following unexpected, high outcomes, and (iii) a reversal of the effect of risk on beta oscillations. These observations are consistent with an impairment in prediction error computation in the medial prefrontal cortex. PMID- 27372216 TI - Increased Cognitive Control During Execution of Finger Tap Movement in People with Parkinson's Disease. AB - BACKGROUND: Previous studies employed demanding and complex hand tasks to study the brain activation in people with Parkinson's Disease (PD). There is inconsistent finding about the cerebellar activity during movement execution of this patient population. OBJECTIVES: This study aimed to examine the brain activation patterns of PD individuals in the on-state and healthy control subjects in a simple finger tapping task. METHODS: Twenty-seven patients with PD and 22 age-matched healthy subjects were recruited for the study. Subjects were instructed to perform simple finger tapping tasks under self- and cue-initiated conditions in separate runs while their brain activations were captured using fMRI. RESULTS: Healthy subjects had higher brain activity in contralateral precentral gyrus during the self-initiated task, and higher brain activity in the ipsilateral middle occipital gyrus during the cue-initiated task. PD patients had higher brain activity in the cerebellum Crus I (bilateral) and lobules VI (ipsilateral) during the self-initiated task and higher brain activity in the contralateral middle frontal gyrus during the cue-initiated task. When compared with healthy controls, PD patients had lower brain activity in the contralateral inferior parietal lobule during the self-initiated task, and lower brain activity in the ipsilateral cerebellum lobule VIII, lobule VIIB and vermis VIII, and thalamus during the cue-initiated task. Conjunction analysis indicated that both groups had activation in bilateral cerebellum and SMA and ipsilateral precentral gyrus and postcentral gyrus during both self- and cue-initiated movement. Individuals with PD exhibited higher brain activity in the executive zone (cerebellum Crus I and II) during self-initiated movement, and lower brain activity in the sensorimotor zone (i.e. lobule VIIb and VIII of the cerebellum) during cue-initiated movement. DISCUSSIONS: The findings suggest that individuals with PD may use more executive control when performing simple movements. PMID- 27372217 TI - Corrigendum to "Quantifying the strength of miRNA-target interactions" [Methods (2015) 90-99]. PMID- 27372218 TI - Does substance use moderate the association of neighborhood disadvantage with perceived stress and safety in the activity spaces of urban youth? AB - BACKGROUND: This study investigates the association of activity space-based exposure to neighborhood disadvantage with momentary perceived stress and safety, and the moderation of substance use on those associations, among a sample of 139 urban, primarily African American, adolescents. METHOD: Geospatial technologies are integrated with Ecological Momentary Assessment (EMA) to capture exposure to neighborhood disadvantage and perceived stress and safety in the activity space. A relative neighborhood disadvantage measure for each subject is calculated by conditioning the neighborhood disadvantage observed at the EMA location on that of the home neighborhood. Generalized estimating equations (GEE) are used to model the effect of relative neighborhood disadvantage on momentary perceived stress and safety, and the extent to which substance use moderates those associations. RESULTS: Relative neighborhood disadvantage is significantly associated with higher perceived stress, lower perceived safety, and greater substance use involvement. The association of relative neighborhood disadvantage with stress is significantly stronger among those with greater substance use involvement. CONCLUSION: This research highlights the value of integrating geospatial technologies with EMA and developing personalized measures of environmental exposure for investigating neighborhood effects on substance use, and suggests substance use intervention strategies aimed at neighborhood conditions. Future research should seek to disentangle the causal pathways of influence and selection that relate neighborhood environment, stress, and substance use, while also accounting for the role of gender and family and peer social contexts. PMID- 27372220 TI - Decreased diversion by doctor-shopping for a reformulated extended release oxycodone product (OxyContin). AB - BACKGROUND: Doctor-shopping (obtaining prescriptions from multiple prescribers/pharmacies) for opioid analgesics produces a supply for diversion and abuse, and represents a major public health issue. METHODS: An open cohort study assessed changes in doctor-shopping in the U.S. for a brand extended release (ER) oxycodone product (OxyContin) and comparator opioids before (July, 2009 to June, 2010) versus after (January, 2011 to June, 2013) introduction of reformulated brand ER oxycodone with abuse-deterrent properties, using IMS LRx longitudinal data covering >150 million patients and 65% of retail U.S. prescriptions. RESULTS: After its reformulation, the rate of doctor-shopping decreased 50% (for 2+ prescribers/3+ pharmacies) for brand ER oxycodone, but not for comparators. The largest decreases in rates occurred among young adults (73%), those paying with cash (61%) and those receiving the highest available dose (62%), with a 90% decrease when stratifying by all three characteristics. The magnitude of doctor shopping reductions increased with increasing number of prescribers/pharmacies (e.g., 75% reduction for >=2 prescribers/>=4 pharmacies). CONCLUSIONS: The rate of doctor-shopping for brand ER oxycodone decreased substantially after its reformulation, which did not occur for other prescription opioids. The largest reductions in doctor-shopping occurred with characteristics associated with higher abuse risk such as youth, cash payment and high dose, and with more specific thresholds of doctor-shopping. A higher prescriber and/or pharmacy threshold also increased the magnitude of the decrease, suggesting that it better captured the effect of the reformulation on actual doctor-shoppers. PMID- 27372221 TI - Cost-utility analysis of an integrated care model for multimorbid patients based on a clinical trial. AB - OBJECTIVE: To conduct a cost-utility analysis on an integrated healthcare model comprising an assigned internist and a hospital liaison nurse for patients with multimorbidity, compared to a conventional reactive healthcare system. METHODS: A cluster randomised clinical trial was conducted. The model consisted of a reference internist and a liaison nurse, who aimed to improve coordination and communication between levels and to enhance continuity of care after hospitalisation. We recorded sociodemographic data, diagnoses and corresponding clinical categories, functional status, use of healthcare resources and quality of life. Data were collected by reviewing electronic medical records and administering questionnaires. We performed univariate and multivariate analyses both for utilities and total costs. Bootstrapping methods were applied to calculate the confidence ellipses of incremental costs and efficiency. RESULTS: We recruited a total of 140 patients. The model assessed was not found to be efficient in general. We found an incremental cost of ?1,035.90 and an incremental benefit of -0.0762 QALYs for the initiative compared to standard care after adjusting for the main variables. However, the subgroup of patients under 80 years of age with three or more clinical categories resulted in an 89% cost saving in the simulations. CONCLUSIONS: The integrated model was not suitable for all study patients. However, the subgroup analysis identified a narrow target population that should be analysed in future studies. PMID- 27372222 TI - Comparison of ETView SL, Airtraq, and Macintosh laryngoscopes for face-to-face tracheal intubation: a randomized crossover manikin trial. PMID- 27372219 TI - Longitudinal changes in smoking abstinence symptoms and alternative reinforcers predict long-term smoking cessation outcomes. AB - BACKGROUND: Transdermal nicotine, with behavioral counseling, is among the most popular approaches used to quit smoking. Yet, 6-month cessation rates rarely exceed 20-25%. Identifying factors associated with cessation success may help researchers and clinicians develop enhanced interventions that can improve quit rates. This study examined longitudinal changes in withdrawal, craving, depression and anxiety symptoms, and alternative reinforcers, from a baseline assessment to a 6-month outcome, as predictors of 6-month smoking cessation outcomes following 8 weeks of nicotine patch treatment and counseling. METHODS: A sample of 180 smokers, who completed an effectiveness trial that provided counseling and 8 weeks of 21mg nicotine patches, was analyzed. Generalized estimating equations evaluated changes in withdrawal and craving, depression and anxiety symptoms, and alternative reinforcers over time, between participants who were smoking at 6-months and participants who were abstinent (confirmed with carbon monoxide) at 6-months. Multiple logistic regression assessed changes in these variables as predictors of relapse. RESULTS: Controlling for covariates associated with cessation (i.e., nicotine dependence, patch adherence, and rate of nicotine metabolism), participants who were abstinent at 6 months showed significantly lower craving and withdrawal and significantly higher substitute reinforcers from baseline to 6 months, vs. those who were smoking at 6 months (p<0.001). An increase in craving predicted relapse to smoking (p<0.05). CONCLUSIONS: These results support continued efforts to strengthen interventions that reduce withdrawal and craving and the development of interventions to address alternative reinforcers in order to promote long-term smoking abstinence following nicotine patch treatment. PMID- 27372223 TI - Optimal adaptive IMRT strategy to spare the parotid glands in oropharyngeal cancer. AB - PURPOSE: In oropharyngeal cancer adaptive radiation therapy (ART), this study aimed to quantify the dosimetric benefit of numerous replanning strategies, defined by various numbers and timings of replannings, with regard to parotid gland (PG) sparing. MATERIAL AND METHODS: Thirteen oropharyngeal cancer patients had one planning and then six weekly CT scans during the seven weeks of IMRT. Weekly doses were recalculated without replanning or with replanning to spare the PG. Sixty-three ART scenarios were simulated by considering all the combinations of numbers and timings of replanning. The PG cumulated doses corresponding to "standard" IMRT and ART scenarios were estimated and compared, either by calculating the average of weekly doses or using deformable image registration (DIR). RESULTS: Considering average weekly doses, the mean PG overdose using standard IMRT, compared to the planned dose, was 4.1Gy. The mean dosimetric benefit of 6 replannings was 3.3Gy. Replanning at weeks 1, 1-5, 1-2-5, 1-2-4-5 and 1-2-4-5-6 produced the lowest PG mean doses, 94% of the maximum benefit being obtained with 3 replannings. The percentage of patients who had a benefit superior to 5Gy for the contralateral PG was 31% for the three-replannings strategy. The same conclusions were found using DIR. CONCLUSION: Early replannings proved the most beneficial for PG sparing, three replannings (weeks 1 2-5), representing an attractive combination for ART in oropharyngeal cancer. PMID- 27372224 TI - Long-term observations of radiation-induced creatinine clearance reduction and renal parenchymal volume atrophy. AB - PURPOSE: The kidney is a dose-limiting organ for upper abdominal radiotherapy. In this study, radiation-induced kidney injury represented by changes of creatinine clearance (Ccr) and renal parenchymal volume measured by computed tomography (CT) were evaluated by analysing dose-volume histograms (DVHs) in patients with primary gastric diffuse large B-cell lymphoma (PGDLBCL) treated with chemoradiotherapy. MATERIALS AND METHODS: Thirty-eight PGDLBCL patients (seventy six kidneys) treated with chemoradiotherapy were included in this study. At least 4 years of follow-up was required for eligibility. Patients underwent (immuno-) chemotherapy followed by radiotherapy with approximately 40Gy to the whole stomach and perigastric lymph nodes. Ccr and CT were obtained at least annually. Changes of Ccr and renal parenchymal volume before and 4years after radiotherapy were compared using DVH parameters. RESULTS: Mean Ccr decreased significantly from 82.7mL/min (range, 39-124mL/min) before radiotherapy to 70.4mL/min (range, 35-109mL/min) (p=0.01) 4years after radiotherapy. Mean reduction of bilateral renal parenchymal volume was 12% (range, -5-37%) in the same time period. Ccr and renal parenchymal volume tended to lower over time more than 4years after radiotherapy. Concerning DVH analysis, V20Gy?26.6% and D30%?19Gy had a significant risk of bilateral renal atrophy of ?14% and reduction of the Ccr?20mL/min. CONCLUSION: This study revealed that there was a definite relationship between DVH, renal atrophy and Ccr reduction. V20Gy<26.6% and D30%<19Gy appeared to be safe dose constraints for a Ccr reduction of <20mL/min 4years after radiotherapy. PMID- 27372225 TI - Risk factors for the development of active methicillin-resistant Staphylococcus aureus (MRSA) infection in patients colonized with MRSA at hospital admission. AB - BACKGROUND: Patients who present to Veterans Affairs hospitals are screened for methicillin-resistant Staphylococcus aureus (MRSA) colonization. Those who test positive are isolated during their hospital stay. However, it is unknown which of these patients are most likely to subsequently develop active MRSA infections. METHODS: This retrospective case-control study characterized risk factors for active MRSA infection among patients colonized with MRSA at hospital admission. Potential demographic and clinical risk factors were identified using electronic queries and manual chart abstraction; data were compared by standard statistical tests, and variables with P <= .05 in bivariable analysis were entered into a multivariable logistic regression model. RESULTS: There were 71 cases and 213 controls. Risk factors associated with MRSA infection included diabetes mellitus with or without end organ damage (26% vs 14%, P = .02), hemiplegia (9% vs 2%, P = .01), chronic kidney disease (33% vs 20%, P = .03), postcolonization inpatient admission within 90 days (44% vs 29%, P = .03), surgery (41% vs 9%, P < .01), and dialysis (10% vs 3%, P = .02). On multivariable analysis, surgery during follow up, dialysis during follow-up, and hemiplegia remained significant. CONCLUSIONS: Among patients with MRSA colonization, surgery or dialysis during follow-up and history of hemiplegia were associated with subsequent MRSA infection. Knowledge of these risk factors may allow for future targeted interventions to prevent MRSA infections among colonized patients. PMID- 27372226 TI - Persistent racial and ethnic disparities in flu vaccination coverage: Results from a population-based study. AB - BACKGROUND: The Advisory Committee on Immunization Practices recommends annual flu vaccination for all adults. We aimed to identify predictors of receiving a flu vaccination, with an emphasis on the impact of race and ethnicity. METHODS: We used data from the 2011-2012 California Health Interview Survey and included all individuals aged >=18 years. We performed a survey-weighted logistic regression on receipt of flu vaccination within the last year, adjusted by demographic and socioeconomic variables, and calculated odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Our study included a population-weighted sample of 27,796,484 individuals. Overall, 35.8% received a flu vaccination within the last year. Blacks were 33% less likely (95% CI, 21%-43%) to have been vaccinated than whites. Conversely, Koreans (OR, 1.77; 95% CI, 1.35-2.33) and Vietnamese (OR, 1.57; 95% CI, 1.19-2.07) were more likely than whites to have been vaccinated. No differences were seen between whites and the remaining racial and ethnic groups (Latino, Japanese, Chinese, Filipino, South Asian, Asian other, and other). CONCLUSIONS: Racial and ethnic disparities in flu vaccination uptake exist in California. Namely, blacks have lower vaccination rates than whites, and there are disparate vaccination rates among the Asian-American subgroups. Efforts to increase vaccination rates among these groups are needed. PMID- 27372227 TI - Clostridium difficile infection epidemiology and management: Comparison of results of a prospective study with a retrospective one in a reference teaching and research hospital in Northern Italy. AB - BACKGROUND: Clostridium difficile-associated disease (CDAD) is the most common infectious antibiotic-associated diarrhea and is a growing health care problem. Prevention of Clostridium difficile infection focuses on clinical and epidemiologic infection control measures. METHODS: Between 2008 and 2009, we conducted a retrospective study that showed an incidence of CDAD among the highest reported in the literature. Subsequently, we developed a preventive protocol that was adopted in our hospital in 2010. We then conducted a prospective study to investigate prevalence, incidence, and mortality of CDAD and to compare the results with those of the retrospective study, evaluating adherence to preventive measures and their efficacy. RESULTS: In both studies, prevalence and incidence significantly increased in older patients. Crude prevalence was similar in the 2 studies. The incidence rate increased by 36%, with a significant increase only in the C and D wards. In-hospital mortality rose in both prevalent and incident cases. Regarding adhesion to hospital protocol, 77% of prevalent cases were treated with the required procedure. The highest percentage of isolated patients was achieved in C and D wards. In these wards we detected lower training hours per nurse. However, in 2013, we observed a significant decrease in incidence of CDAD and found a hospital prevalence of 0.33%. CONCLUSIONS: Health care personnel education could be more important than the possibility of isolating infected patients in single rooms. PMID- 27372228 TI - [Standard of care of carcinomas on cancer of unknown primary site in 2016]. AB - Patients with Cancer of unknown primary (cup) represent 2-10%, and have disseminated cancers for which we cannot find the primary site despite the clinical, pathological and radiological exams at our disposal. Diagnosis is based on a thorough clinical and histopathologic examination as well as new imaging techniques. Several clinicopathologic entities requiring specific treatment can be identified. Genome sequencing and liquid biopsy (circulating tumor cells and tumor free DNA) could allow further advances in the diagnosis. Therapeutically, in addition to surgery, radiotherapy and chemotherapy, precision medicine provides new therapeutic approaches. PMID- 27372229 TI - Unpaid carers: where is public health? PMID- 27372230 TI - Redesign and commissioning of sexual health services in England - a qualitative study. AB - OBJECTIVES: Responsibility for the commissioning of sexual and reproductive health (SRH) services transferred from the National Health Service to local authorities in England in 2013. This transfer prompted many local authorities to undertake new procurements of these SRH services. This study was undertaken to capture some of the lessons learnt in order to inform future commissioning and system redesign. STUDY DESIGN: A qualitative study was carried out involving semi structured interviews. METHODS: Interviews were conducted with 13 local authority sexual health commissioners in Yorkshire and the Humber from 11 interviews. Thematic analysis was used to identify themes from transcripts of the interviews with the 13 participants. RESULTS: Key themes identified were as follows: the challenge and complexity to those new to clinical commissioning; the prerequisites of robust infrastructural inputs to undertake the process, including technical expertise, a dependable project team, with clarity over the timescales and the budget; the requirement for good governance, stakeholder engagement and successful management of relationships with the latter; and the need to focus on the outcomes, aiming for value for money and improved system performance. CONCLUSIONS: Several key issues emerged from our study that significantly influenced the outcome of the redesign and commissioning process for sexual health services. An adapted model of the Donabedian evaluation framework was developed to provide a tool to inform future system redesign. Our model helps identify the key determinants for successful redesign in this context which is essential to both mitigate potential risks and maximize the likelihood of successful outcomes. Our model may have wider applications. PMID- 27372231 TI - Successful revision of involved margins under frozen section control. PMID- 27372232 TI - Skeletal stability after sagittal split ramus osteotomy with physiological positioning in patients with skeletal mandibular prognathism and facial asymmetry. AB - The correction of deformities of the jaw in patients with facial asymmetry is challenging because of the high rate of relapse, which may partly be caused by skeletal interference and inappropriate seating of the condylar head. We evaluated outcomes in 30 patients who were treated by short lingual osteotomy with physiological positioning. Nine had facial symmetry (absolute displacement of the menton<2mm), 14 had minor asymmetry (displacement of >2 to <4mm), and 7 severe asymmetry (displacement of >4mm). The postoperative position of the menton (Me) was stable in each group, but deviated by 3.56mm in those with severe asymmetry. This deviation remained immediately after operation and after more than one year in this group, which implies that the Me was not on the mandibular midline. The lateral swing of both sides of the proximal segment did not change immediately after operation in any group. Although short lingual osteotomy with physiological positioning can result in skeletal stability, it is important to assess the association between the dental arch and the mandible using computed tomography to ensure a good outcome in patients with a skeletal class III deformity and facial asymmetry. PMID- 27372233 TI - Unilateral complex syngnathia of the maxilla, mandible, and zygomatic complex in a newborn baby. PMID- 27372234 TI - Compliance With the Healthy Eating Standards in YMCA After-School Programs. AB - OBJECTIVE: In 2011, the YMCA of the US adopted Healthy Eating standards for all of their after-school programs (ASPs). The extent to which YMCA ASPs comply with the standards is unknown. METHODS: Twenty ASPs from all YMCA ASPs across South Carolina (N = 102) were invited to participate. Direct observation of the food and beverages served and staff behaviors were collected on 4 nonconsecutive days per ASP. RESULTS: One ASP did not serve a snack. Of the remaining ASPs, a total of 26% served a fruit or vegetable and 32% served water every day; 26% served sugar-sweetened beverages, 47% served sugar-added foods, and only 11% served whole grains when grains were served. Staff members sat with the children (65%) or verbally promoted healthy eating (15%) on at least 1 observation day. Staff drank non-approved drinks (25%) or foods (45%) on at least 1 observation day. No ASPs served snacks family-style every day. CONCLUSIONS AND IMPLICATIONS: Additional efforts are required to assist YMCA-operated ASPs in achieving these important nutrition standards. PMID- 27372235 TI - Red-light running violation prediction using observational and simulator data. AB - In the United States, 683 people were killed and an estimated 133,000 were injured in crashes due to running red lights in 2012. To help prevent/mitigate crashes caused by running red lights, these violations need to be identified before they occur, so both the road users (i.e., drivers, pedestrians, etc.) in potential danger and the infrastructure can be notified and actions can be taken accordingly. Two different data sets were used to assess the feasibility of developing red-light running (RLR) violation prediction models: (1) observational data and (2) driver simulator data. Both data sets included common factors, such as time to intersection (TTI), distance to intersection (DTI), and velocity at the onset of the yellow indication. However, the observational data set provided additional factors that the simulator data set did not, and vice versa. The observational data included vehicle information (e.g., speed, acceleration, etc.) for several different time frames. For each vehicle approaching an intersection in the observational data set, required data were extracted from several time frames as the vehicle drew closer to the intersection. However, since the observational data were inherently anonymous, driver factors such as age and gender were unavailable in the observational data set. Conversely, the simulator data set contained age and gender. In addition, the simulator data included a secondary (non-driving) task factor and a treatment factor (i.e., incoming/outgoing calls while driving). The simulator data only included vehicle information for certain time frames (e.g., yellow onset); the data did not provide vehicle information for several different time frames while vehicles were approaching an intersection. In this study, the random forest (RF) machine learning technique was adopted to develop RLR violation prediction models. Factor importance was obtained for different models and different data sets to show how differently the factors influence the performance of each model. A sensitivity analysis showed that the factor importance to identify RLR violations changed when data from different time frames were used to develop the prediction models. TTI, DTI, the required deceleration parameter (RDP), and velocity at the onset of a yellow indication were among the most important factors identified by both models constructed using observational data and simulator data. Furthermore, in addition to the factors obtained from a point in time (i.e., yellow onset), valuable information suitable for RLR violation prediction was obtained from defined monitoring periods. It was found that period lengths of 2-6m contributed to the best model performance. PMID- 27372237 TI - Internal adaptation of resin composites at two configurations: Influence of polymerization shrinkage and stress. AB - OBJECTIVE: This study compared internal adaptation of composites under different C-factors and examined the relationship between internal adaptation and polymerization shrinkage parameters. METHODS: Cylindrical cavities 3mm in diameter were prepared in 100 human third molars in two depths: 4mm high C-factor (H-CF) or 1mm low C-factor (L-CF). After adhesive application (Clearfil SE One, Kuraray Noritake), the composite was placed in two increments in three subgroups: Filtek Supreme (FS, 3M ESPE); Charisma Diamond (CD, Heraeus Kulzer); Amelogen Plus (AP, Ultradent); and as a single increment in two subgroups: Tetric EvoCeram Bulk Fill (TB, Ivoclar Vivadent) and Venus Bulk Fill (VB, Heraeus Kulzer). After thermo-mechanical load-cycles, imperfect margin percentage (%IM) was calculated using swept-source optical coherence tomography (SS-OCT) imaging. The relationships between %IM and linear shrinkage (LS) and shrinkage stress, measured under either zero-compliance (PS0) or compliance-allowed (PS) conditions were evaluated. RESULTS: The %IM was significantly different between H-CF and L CF groups. The %IM in H-CF turned out to be as groups CD, FS<=TB0.05). Only the composite containing 5.0% of fibers presented lower FS than the control (p<0.001). FT increased significantly between the control (1.3+/ 0.17MPam(0.5)) and the composites containing either 5.0% (2.7+/-0.6MPam(0.5)) or 7.5% of fibers (2.8+/-0.6MPam(0.5), p<0.001). PS in relation to control was significantly reduced at 2.5% fibers (from 0.81+/-0.13% to 0.57+/-0.13%) and further reduced between 5.0% and 7.5% (from 0.42+/-0.12% to 0.23+/-0.07%, p<0.001). SIGNIFICANCE: The replacement of a small fraction of filler particles with glass fibers significantly increased fracture toughness and reduced post-gel shrinkage of experimental composites. PMID- 27372239 TI - Impaired functional default mode network in patients with mild neurological Wilson's disease. AB - Wilson's disease (WD) is an autosomal recessive metabolic disorder characterized by cognitive, psychiatric and motor signs and symptoms that are associated with structural and pathological brain abnormalities, in addition to liver changes. However, functional brain connectivity pattern of WD patients remains largely unknown. In the present study, we investigated functional brain connectivity pattern of WD patients using resting state functional magnetic resonance imaging. Particularly, we studied default mode network (DMN) using posterior cingulate cortex (PCC) based seed functional connectivity analysis and graph theoretic functional brain network analysis tools, and investigated the relationship between the DMN's functional connectivity pattern of WD patients and their attention functions examined using the attention network test (ANT). Our results demonstrated that WD patients had altered DMN's functional connectivity and lower local and global network efficiency compared with normal controls (NCs). In addition, the functional connectivity between left inferior temporal cortex and right lateral parietal cortex was correlated with altering function, one of the attention functions, across WD and NC subjects. These findings indicated that the DMN's functional connectivity was altered in WD patients, which might be correlated with their attention dysfunction. PMID- 27372240 TI - Exploring cortical atrophy and its clinical and biochemical correlates in Wilson's disease using voxel based morphometry. AB - OBJECTIVES: To determine cortical grey matter (GM) changes and their clinical and biochemical correlates in patients with Wilson's disease using voxel based morphometry (VBM). METHODS: Clinical and imaging data of 10 patients (all male, mean age 16.0 +/- 6.3years) with Wilson's Disease were analyzed. T1W volumetric MRI data of patients without obvious cortical atrophy or signal changes on conventional MRI was compared with MRI of 11 matched control subjects using VBM analysis with Statistical Parametric Mapping 8. Results were expressed at statistical threshold of p < 0.05 (FWE corrected) and p < 0.001 (uncorrected). Multiple regression analysis was done to analyze possible relation between GM atrophy, duration of disease and biochemical abnormalities. RESULTS: Compared to controls, patients showed scattered areas of reduced GM volume in bilateral caudate head, medial part of right globus pallidus and body of right caudate (FWE corrected p < 0.05). At p < 0.001(uncorrected) widespread areas of cortical atrophy were also noted involving the frontal and temporal lobes, lentiform nuclei, cerebellum and thalamus. Significant positive correlation (uncorrected p < 0.001) were noted between (i) duration of disease and cortical GM volume of frontal, parietal and temporal lobes and cerebellum (ii) serum copper levels and GM volume of right medial frontal gyrus and paracentral lobule. CONCLUSIONS: To the best of our knowledge, this is the first VBM study in patients with Wilson's disease. In spite of apparently normal cortex on visual inspection of MRI, decreased cortical GM volume was detected using VBM. In addition, serum copper may act as surrogate marker of cortical abnormalities in Wilson's disease. PMID- 27372242 TI - Disseminated choroid plexus papillomas in adults: A case series and review of the literature. AB - Choroid plexus papillomas (CPPs) are uncommon, usually intraventricular, low grade tumors, accounting for less than 1% of all intracranial neoplasms and 2-4% of brain tumors in children. Dissemination of CPPs to multiple levels of the neuraxis has been seldom observed. Thus far, only 26 adult patients have been reported in the English language literature. With some exceptions, disseminated CPPs have been observed in adults and involved multiple sites along the cerebrospinal fluid pathways. Occasionally, intraparenchymal extension has been documented, and secondary involvement of the suprasellar region has been reported in only five patients. Postoperative treatment of CPPs has not been standardized. Most recommended therapies have been extrapolated from a series of atypical papillomas or carcinomas of the choroid plexus in children. We herein report a series of three patients of disseminated choroid plexus papillomas providing additional insights into this relatively rare entity. PMID- 27372241 TI - Cancer in Parkinson's disease. AB - INTRODUCTION: We examined the prevalence of cancer in patients with Parkinson's disease (PD) and controls evaluated at the Mayo Clinic in Jacksonville, Florida, between 2003 and 2014. METHODS: We retrospectively collected information regarding cancer diagnoses and diagnosis of PD from 971 unrelated PD patients and 478 controls, and all were white. For PD patients, we examined cancers diagnosed before and after PD diagnosis separately in addition to considering all cancer diagnoses. RESULTS: Twenty different cancers were identified. In PD patients, the most common types of cancer were skin cancer (17.3% overall; 10.6% before PD), followed by nonmelanoma skin cancer (16.0% overall; 9.7% before PD), prostate cancer in men (12.8% overall; 9.2% before PD), breast cancer in women (10.6% overall; 6.3% before PD), and melanoma (2.4% overall; 1.1% before PD). Compared to controls, a significantly lower frequency of nonmelanoma skin cancer (odds ratio [OR]: 0.62, P = 0.0024) and any skin cancer (OR: 0.57, P = 0.0002) was observed in PD patients. These differences were greater when considering only cases with cancers that occurred before PD diagnosis (OR: 0.49, P < 0.0001; OR: 0.45, P < 0.0001, respectively), and there was a lower frequency of melanoma and any cancer preceding PD diagnosis compared to controls (OR: 0.31, P = 0.003; OR: 0.36, P < 0.0001). There was no evidence of a frequency difference for any other cancer. CONCLUSIONS: PD patients had a lower frequency of skin cancers or any cancer prior to PD diagnosis compared to controls, suggesting that cancer may have a protective effect on PD risk. PMID- 27372245 TI - Author Reply. PMID- 27372243 TI - Oxygen Sensing via the Ethylene Response Transcription Factor RAP2.12 Affects Plant Metabolism and Performance under Both Normoxia and Hypoxia. AB - Subgroup-VII-ethylene-response-factor (ERF-VII) transcription factors are involved in the regulation of hypoxic gene expression and regulated by proteasome mediated proteolysis via the oxygen-dependent branch of the N-end-rule pathway. While research into ERF-VII mainly focused on their role to regulate anoxic gene expression, little is known on the impact of this oxygen-sensing system in regulating plant metabolism and growth. By comparing Arabidopsis (Arabidopsis thaliana) plants overexpressing N-end-rule-sensitive and insensitive forms of the ERF-VII-factor RAP2.12, we provide evidence that oxygen-dependent RAP2.12 stability regulates central metabolic processes to sustain growth, development, and anoxic resistance of plants. (1) Under normoxia, overexpression of N-end-rule insensitive Delta13RAP2.12 led to increased activities of fermentative enzymes and increased accumulation of fermentation products, which were accompanied by decreased adenylate energy states and starch levels, and impaired plant growth and development, indicating a role of oxygen-regulated RAP2.12 degradation to prevent aerobic fermentation. (2) In Delta13RAP2.12-overexpressing plants, decreased carbohydrate reserves also led to a decrease in anoxic resistance, which was prevented by external Suc supply. (3) Overexpression of Delta13RAP2.12 led to decreased respiration rates, changes in the levels of tricarboxylic acid cycle intermediates, and accumulation of a large number of amino acids, including Ala and gamma-amino butyric acid, indicating a role of oxygen-regulated RAP2.12 abundance in controlling the flux-modus of the tricarboxylic acid cycle. (4) The increase in amino acids was accompanied by increased levels of immune-regulatory metabolites. These results show that oxygen-sensing, mediating RAP2.12 degradation is indispensable to optimize metabolic performance, plant growth, and development under both normoxic and hypoxic conditions. PMID- 27372244 TI - Genome-Scale Metabolic Model for the Green Alga Chlorella vulgaris UTEX 395 Accurately Predicts Phenotypes under Autotrophic, Heterotrophic, and Mixotrophic Growth Conditions. AB - The green microalga Chlorella vulgaris has been widely recognized as a promising candidate for biofuel production due to its ability to store high lipid content and its natural metabolic versatility. Compartmentalized genome-scale metabolic models constructed from genome sequences enable quantitative insight into the transport and metabolism of compounds within a target organism. These metabolic models have long been utilized to generate optimized design strategies for an improved production process. Here, we describe the reconstruction, validation, and application of a genome-scale metabolic model for C. vulgaris UTEX 395, iCZ843. The reconstruction represents the most comprehensive model for any eukaryotic photosynthetic organism to date, based on the genome size and number of genes in the reconstruction. The highly curated model accurately predicts phenotypes under photoautotrophic, heterotrophic, and mixotrophic conditions. The model was validated against experimental data and lays the foundation for model driven strain design and medium alteration to improve yield. Calculated flux distributions under different trophic conditions show that a number of key pathways are affected by nitrogen starvation conditions, including central carbon metabolism and amino acid, nucleotide, and pigment biosynthetic pathways. Furthermore, model prediction of growth rates under various medium compositions and subsequent experimental validation showed an increased growth rate with the addition of tryptophan and methionine. PMID- 27372246 TI - Editorial Comment. PMID- 27372247 TI - Erratum. PMID- 27372248 TI - Remediation of aquaculture water in the estuarine wetlands using coal cinder zeolite balls/reed wetland combination strategy. AB - In this paper, the modified coal cinders and zeolite powders in proportion of 2:1 were mixed with modified polyvinyl alcohol (PVA) with a ratio of 20:1 (w/v) to make a new sorbent and biological carrier-the coal cinder-zeolite balls (CCZBs). The maximum absorption capacities of ammonia nitrogen and Chemical Oxygen Demand (CODCr) on CCZBs, adsorption process were evaluated in batch experiments. And then they were combined with reed wetland for bioremediation of micro-polluted aquaculture water in estuarine wetlands. The results showed that the removal efficiencies of ammonia nitrogen and CODCr improved with the decrease in water inflow and increase in inflow concentrations. Efficiencies of 67.3% and 71.3% for ammonia nitrogen and CODCr under water flow of 10 L/h were obtained when their inflow concentrations were 1.77 and 56.0 mg/L respectively. This strategy can be served as a model system for bioremediation in situ of aquaculture water and other organic polluted or eutrophic water. PMID- 27372249 TI - Elimination of textile dyes using activated carbons prepared from vegetable residues and their characterization. AB - In this study, three mesoporous activated carbons prepared from vegetable residues were used to remove acid, basic, and direct dyes from aqueous solutions, and reactive and vat dyes from textile wastewater. Granular carbons obtained by chemical activation at 673 K with phosphoric acid from prickly pear peels (CarTunaQ), broccoli stems (CarBrocQ), and white sapote seeds (CarZapQ) were highly efficient for the removal of dyes. Adsorption equilibrium studies were carried out in batch systems and treated with Langmuir and Freundlich isotherms. The maximum adsorption capacities calculated from the Langmuir isotherms ranged between 131.6 and 312.5 mg/g for acid dyes, and between 277.8 and 500.0 mg/g for basic dyes at 303 K. Our objective in this paper was to show that vegetable wastes can serve as precursors for activated carbons that can be used for the adsorption of dyes. Specifically CarBrocQ was the best carbon produced for the removal of textile dyes. The color removal of dyes present in textile wastewaters was compared with that of a commercial powdered carbon, and it was found that the carbons produced using waste material reached similar efficiency levels. Carbon samples were characterized by bulk density, point of zero charge, thermogravimetric analysis, elemental analysis, Fourier transform infrared spectroscopy, scanning electron microscopy, methylene blue adsorption isotherms at 303 K, and nitrogen adsorption isotherms at 77 K (SBET). The results show that the activated carbons possess a large specific surface area (1025-1177 m(2)/g) and high total pore volume (1.06-2.16 cm(3)/g) with average pore size diameters between 4.1 and 8.4 nm. Desorption and regeneration tests were made to test the viability of reusing the activated carbons. PMID- 27372250 TI - Models of reforestation productivity and carbon sequestration for land use and climate change adaptation planning in South Australia. AB - Environmental management and regional land use planning has become more complex in recent years as growing world population, climate change, carbon markets and government policies for sustainability have emerged. Reforestation and agroforestry options for environmental benefits, carbon sequestration, economic development and biodiversity conservation are now important considerations of land use planners. New information has been collected and regionally-calibrated models have been developed to facilitate better regional land use planning decisions and counter the limitations of currently available models of reforestation productivity and carbon sequestration. Surveys of above-ground biomass of 264 reforestation sites (132 woodlots, 132 environmental plantings) within the agricultural regions of South Australia were conducted, and combined with spatial information on climate and soils, to develop new spatial and temporal models of plant density and above-ground biomass productivity from reforestation. The models can be used to estimate productivity and total carbon sequestration (i.e. above-ground + below-ground biomass) under a continuous range of planting designs (e.g. variable proportions of trees and shrubs or plant densities), timeframes and future climate scenarios. Representative spatial models (1 ha resolution) for 3 reforestation designs (i.e. woodlots, typical environmental planting, biodiverse environmental plantings) * 3 timeframes (i.e. 25, 45, 65 years) * 4 possible climates (i.e. no change, mild, moderate, severe warming and drying) were generated (i.e. 36 scenarios) for use within land use planning tools. PMID- 27372251 TI - Accounting for substitution and spatial heterogeneity in a labelled choice experiment. AB - Many environmental valuation studies using stated preferences techniques are single-site studies that ignore essential spatial aspects, including possible substitution effects. In this paper substitution effects are captured explicitly in the design of a labelled choice experiment and the inclusion of different distance variables in the choice model specification. We test the effect of spatial heterogeneity on welfare estimates and transfer errors for minor and major river restoration works, and the transferability of river specific utility functions, accounting for key variables such as site visitation, spatial clustering and income. River specific utility functions appear to be transferable, resulting in low transfer errors. However, ignoring spatial heterogeneity increases transfer errors. PMID- 27372252 TI - Effects of solids retention time on the fate of tetracycline resistance in SBRs for the treatment of carcass leachate. AB - In the event of a foot and mouth disease outbreak, further spread of the virus is generally prevented by culling of infected animals in burial pits. This practice may eventually lead to groundwater contamination through leaching of wastewater from the animal carcasses. Wastewater from carcass leachate often contains antibiotic resistant bacteria and genes as well as traces of pharmaceuticals, and a high nutrient content. The role of operational parameters used in activated sludge treatment of this wastewater in the spread of antibiotic resistance has not been fully understood. This study investigated the fate of tetracycline resistant bacteria and genes in sequencing batch reactors with synthetic carcass leachate at different solid retention times. Escherichia coli DH5alpha was used as the representative tetracycline-resistant bacteria with multiple antibiotic resistant genes encoded in plasmid pB10. Solids retention time contributed to an increase in antibiotic resistance in SBRC (SRT = 25 days) with TRB values up to 1.25 * 10(7) CFU/mL which is one log higher than the influent. Microbial community analysis of the DNA samples from effluent of SBRC showed four major phyla: Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria under which are ecologically-important microbial species. It was shown that antibiotic resistance genes cannot be eliminated during treatment of synthetic carcass leachate in a lab-scale sequencing batch reactor. PMID- 27372253 TI - Mercury contamination in deposited dust and its bioaccumulation patterns throughout Pakistan. AB - Mercury (Hg) contamination of environment is a major threat to human health in developing countries like Pakistan. Human populations, particularly children, are continuously exposed to Hg contamination via dust particles due to the arid and semi-arid climate. However, a country wide Hg contamination data for dust particles is lacking for Pakistan and hence, human populations potentially at risk is largely unknown. We provide the first baseline data for total mercury (THg) contamination into dust particles and its bioaccumulation trends, using scalp human hair samples as biomarker, at 22 sites across five altitudinal zones of Pakistan. The human health risk of THg exposure via dust particles as well as the proportion of human population that are potentially at risk from Hg contamination were calculated. Our results indicated higher concentration of THg in dust particles and its bioaccumulation in the lower Indus-plain agricultural and industrial areas than the other areas of Pakistan. The highest THg contamination of dust particles (3000ppb) and its bioaccumulation (2480ppb) were observed for the Lahore district, while the highest proportion (>40%) of human population was identified to be potentially at risk from Hg contamination from these areas. In general, children were at higher risk of Hg exposure via dust particles than adults. Regression analysis identified the anthropogenic activities, such as industrial and hospital discharges, as the major source of Hg contamination of dust particles. Our results inform environmental management for Hg control and remediation as well as the disease mitigation on potential hotspots. PMID- 27372254 TI - The ACIPS: Moving forward in the assessment of negative symptoms. PMID- 27372255 TI - News from the graveyard: Neuropathological research on schizophrenia is alive and productive. PMID- 27372256 TI - Syncope in the young athlete: Assessment of prognosis in subjects with hypertrophic cardiomyopathy. AB - Syncope is a common but concerning event in young athletes. Although mostly due to benign reflex causes, syncope may be arrhythmic and precede sudden cardiac death. Efforts must therefore be made to distinguish post-exertional syncope from syncope during exercise, which can be an ominous sign of a possible underlying heart disease, such as hypertrophic cardiomyopathy. Prevention requires cooperation between physician and athlete, in order to identify individuals at risk and to protect them from sudden death. Solving this diagnostic dilemma may lead to recommendations for athletes to be cleared to play or disqualified from competitive sports, and presents challenging and controversial decisions to the health care provider that can prove difficult to implement. Although exercise contributes to physical and psychological well-being, there are insufficient data to indicate whether an athlete with hypertrophic cardiomyopathy diagnosed after a syncopal episode can safely resume competitive physical activity. The purpose of this study was to review the literature on syncope in young athletes and its relationship to individuals with hypertrophic cardiomyopathy, in order to enable accurate assessment of prognosis and the possibility of resuming competitive sports. PMID- 27372257 TI - Clinical care ratios: quantifying clinical versus non-clinical care for allied health professionals. AB - Objective Clinical care ratios (CCRs) are a useful tool that can be used to quantify and benchmark the clinical and non-clinical workloads of allied health professionals. The purpose of this study was to determine if CCRs are influenced by level of seniority, type of role or profession. This will provide meaningful information for allied health service managers to better manage service demand and capacity. Method Data was collected from 2036 allied health professionals from five professions across 11 Australian tertiary hospitals. Mean (95% confidence intervals) CCRs were calculated according to profession, seniority and role type. A two-way ANOVA was performed to assess the association of CCRs (dependent variable) with seniority level and profession (independent variables). Post-hoc pairwise comparisons identified where significant main or interaction effects occurred (alpha=0.05). Results Significant main effects for seniority level and profession were identified (P<0.05), but there was no interaction effect. Post-hoc comparisons revealed significant differences between all tier combinations (P<0.05) with more senior staff having the lowest CCRs. Conclusion The direct and non-direct clinical components of the allied health professional's workload can be quantified and benchmarked with like roles and according to seniority. The benchmarked CCRs for predominantly clinical roles will enable managers to compare and evaluate like roles and modify non-direct clinical components according to seniority and discipline. What is known about the topic? CCRs are a useful tool to quantify, monitor and compare workloads of allied health professionals. They are thought to change with increased seniority of roles. The CCRs for different allied health professional roles has yet to be defined in the literature. What does this paper add? CCRs decrease as level of seniority increases, indicating higher seniority increases non-clinical time. CCRs differ across professions, suggesting that benchmarking with CCRs must be profession specific. What are the implications for practitioners? The direct and non-direct clinical components of a workload can be quantified, defined and benchmarked with like roles to ensure cost-effective and optimal service delivery and patient outcomes. PMID- 27372258 TI - Biosimilars: A new scenario in biologic therapies. AB - There is no doubt that biologic therapies provide added value for health systems. However, due to their special nature, they also raise some questions that make highly rigorous and demanding quality control and monitoring of their use indispensable. This circumstance is reinforced with the appearance on the scene of biosimilars, which, given their lower cost, are having an increasing impact on the international market. The purpose of this article is to review the major issues posed by their manufacture, distribution and control systems, as well as the most important aspects related to their safety in clinical practice. In this report, we assess the pharmacovigilance of these products, with special attention to traceability, as a key tool to enable earlier detection of adverse events. PMID- 27372259 TI - Social identity, perceived urban neighborhood quality, and physical inactivity: A comparison study of China, Taiwan, and South Korea. AB - Asian countries are currently witnessing unprecedented increase in physical inactivity and subsequent negative health outcomes; however, few cross-country studies documenting this trend exist. This paper presents the findings of a nationally representative sample, based on the East Asian Social Survey in 2011. The study sought to examine the association of social identity factors, such as objective socio-economic position, perceived social status and neighborhood quality with physical inactivity, while controlling for psychosocial and physical health. A sample of 5222 adults living in urban areas across China, Taiwan, and South Korea were surveyed. METHODS: Multivariate nested logistic regressions were constructed. RESULTS: Perceived social status was positively associated with physical activity. Gender difference in physical activity was significant, and this difference widened as educational levels increased. Class division in physical activity was also found. Perceived physical and social features of neighborhood such as suitability for walking and jogging, air quality, and help from neighbors were to different degrees associated with physical inactivity. CONCLUSION: Gender, marital status, education and perceived social status were common factors associated with physical inactivity in East Asian countries. Perceived urban neighborhood quality is particularly important for Chinese people to stay physically active. Cultural-behavioral norms for physical activity associated with gender and social status call for more studies on cultural perspective for health behaviors in cross-cultural contexts. PMID- 27372260 TI - Evaluation of rs62527607 [GT] single nucleotide polymorphism located in BAALC gene in children with acute leukemia using mismatch PCR-RFLP. AB - Acute leukemia is the most common cancer in children and involves several factors that contribute to the development of multidrug resistance and treatment failure. According to our recent studies, the BAALC gene is identified to have high mRNA expression levels in childhood acute lymphoblastic leukemia (ALL) and those with multidrug resistance. Several polymorphisms are associated with the expression of this gene. To date, there has been no study on the rs62527607 [GT] single nucleotide polymorphism (SNP) of BAALC gene and its link with childhood acute lymphoblastic and myeloid leukemia (AML). The purpose of this study is to evaluate the prevalence of this polymorphism in pediatric acute leukemia, as well as its relationship with prognosis. DNA samples were extracted from bone marrow slides of 129 children with ALL and 16 children with AML. The rs62527607 [GT] SNP was evaluated using mismatch polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based analysis. The association between the SNP alleles and patient disease-free survival was then assessed. The prevalence of the T-allele of rs62527607 [GT] SNP in childhood T-ALL and pre-B-ALL was 28.3% and 11.2%, respectively. In the pre-B-ALL patients, 3 year disease free survival was associated with the GG genotype. Results showed a robust association between the rs62527607 SNP and the risk of relapse in ALL, but not AML, patients. T-ALL patients with the GT genotype had an 8.75 fold higher risk of relapse. The current study demonstrates a significant association between the genotype GT and the polymorphic allele G424T, and introduces this SNP as a negative prognostic factor in children with ALL. PMID- 27372261 TI - Adsorption of As(III), As(V) and Cu(II) on zirconium oxide immobilized alginate beads in aqueous phase. AB - A composite adsorbent to remove arsenite [As(III)], arsenate [As(V)], and copper [Cu(II)] from aqueous phase was synthesized by immobilizing zirconium oxide on alginate beads (ZOAB). The composition (wt%) of ZOAB (Zr-34.0; O-32.7; C-21.3; Ca 1.0) was confirmed by energy dispersive X-ray (EDX) analysis. Sorption studies were conducted on single and binary sorbate systems, and the effects of contact time, initial adsorbate concentration, and pH on the adsorption performance of ZOAB (pHPZC = 4.3) were monitored. The sorption process for As(III)/As(V) and Cu(II) reached an equilibrium state within 240 h and 24 h, respectively, with maximum sorption capacities of 32.3, 28.5, and 69.9 mg g(-1), respectively. The addition of Cu(II) was favorable for As(V) sorption in contrast to As(III). In the presence of 48.6 mg L(-1) Cu(II), the sorption capacity of As(V) increased from 1.5 to 3.8 mg g(-1) after 240 h. The sorption data for As(III)/As(V) and Cu(II) conformed the Freundlich and Langmuir isotherm models, respectively. The adsorption of As(III), As(V), and Cu(II) followed pseudo second order kinetics. The effect of arsenic species on Cu(II) sorption was insignificant. The results of present study demonstrated that the synthesized sorbent could be useful for the simultaneous removal of both anionic and cationic contaminants from wastewaters. PMID- 27372262 TI - A hybrid process combining homogeneous catalytic ozonation and membrane distillation for wastewater treatment. AB - A novel catalytic ozonation membrane reactor (COMR) coupling homogeneous catalytic ozonation and direct contact membrane distillation (DCMD) was developed for refractory saline organic pollutant treatment from wastewater. An ozonation process took place in the reactor to degrade organic pollutants, whilst the DCMD process was used to recover ionic catalysts and produce clean water. It was found that 98.6% total organic carbon (TOC) and almost 100% salt were removed and almost 100% metal ion catalyst was recovered. TOC in the permeate water was less than 16 mg/L after 5 h operation, which was considered satisfactory as the TOC in the potassium hydrogen phthalate (KHP) feed water was as high as 1000 mg/L. Meanwhile, the membrane distillation flux in the COMR process was 49.8% higher than that in DCMD process alone after 60 h operation. Further, scanning electron microscope images showed less amount and smaller size of contaminants on the membrane surface, which indicated the mitigation of membrane fouling. The tensile strength and FT-IR spectra tests did not reveal obvious changes for the polyvinylidene fluoride membrane after 60 h operation, which indicated the good durability. This novel COMR hybrid process exhibited promising application prospects for saline organic wastewater treatment. PMID- 27372263 TI - A humic substance analogue AQDS stimulates Geobacter sp. abundance and enhances pentachlorophenol transformation in a paddy soil. AB - Soil humic substances can be used as redox mediators in accelerating the biotransformation of organic pollutants, and humus-respiring bacteria are widely distributed in soils. However, the impact of humic substances on the soil microbial community during the biotransformation of organic pollutants is expected to be crucial while remains to be unclear. In this study, the biostimulation of indigenous microbial communities and the consequent effects on anaerobic transformation of pentachlorophenol (PCP) by a model humic substance, anthraquinone-2,6-disulfonate (AQDS), were systematically investigated in a paddy soil. The addition of AQDS was observed to increase the production of HCl extractable Fe(II) and enhance the PCP transformation rates consequently. The pseudo-first-order rate constants of the PCP transformation showed a positive exponential relationship with the AQDS dosage. The terminal restriction fragment length polymorphism (T-RFLP) results indicated the substantial effect of added AQDS on soil microbial community. The enhanced abundance of Geobacter sp. was disclosed to be most critical for accelerated PCP transformation when with AQDS, in which Geobacter sp. functioned for promoting the generation of active Fe(II) and consequently enhancing the PCP transformation rates. The transformation rates of PCP were exponentially correlated with the abundance of Geobacter sp. positively. The findings are expected to improve the understanding of diversity and ubiquity of microorganisms in humic substances-rich soils for accelerating the transformations of soil chlorinated pollutants. PMID- 27372264 TI - Using aquatic vegetation to remediate nitrate, ammonium, and soluble reactive phosphorus in simulated runoff. AB - Within the agriculturally-intensive Mississippi River Basin of the United States, significant conservation efforts have focused on management practices that reduce nutrient runoff into receiving aquatic ecosystems. Only a small fraction of those efforts have focused on phytoremediation techniques. Each of six different aquatic macrophytes were planted, in monoculture, in three replicate mesocosms (1.2 m * 0.15 m * 0.65 m). Three additional unvegetated mesocosms served as controls for a total number of 21 mesocosms. Over two years, mesocosms were amended once each summer with sodium nitrate, ammonium sulfate, and potassium phosphate dibasic to represent nitrogen and phosphorus in agricultural runoff. System retention was calculated using a simple aqueous mass balance approach. Ammonium retention in both years differed greatly, as Panicum hemitomon and Echinodorus cordifolius retentions were significantly greater than controls in the first year, while only Myriophyllum aquaticum and Typha latifolia were significantly greater than controls in the second year. Greater soluble reactive phosphorus retention was observed in T. latifolia compared to controls in both years. Several other significant differences were observed in either the first or second year, but not both years. In the first year's exposure, P. hemitomon was significantly more efficient than the control, Saururus cernuus, and T. latifolia for overall percent nitrate decrease. Results of this novel study highlight inherent variability within and among species for nutrient specific uptake and the temporal variations of species for nutrient retention. By examining this natural variability, scientists may design phytoremediation systems with greater impact on improving agricultural runoff water quality. PMID- 27372265 TI - Application of UV based advanced oxidation to treat sulfolane in an aqueous medium. AB - Several oxidative methods were studied to degrade sulfolane in an aqueous medium. These include UVA and UVC irradiation with suitable photoactive oxidants, including ozone, H2O2, and TiO2 based photocatalysis and their combinations. Since sulfolane lacks absorption bands in the UV range beyond 200 nm, initiation of reactions depends on the spectra and photochemistry of the oxidants. Among all the advanced oxidation processes investigated, combinations of (a) UVC with H2O2 and O3 (b) UVC with H2O2 and (c) UVC with O3 led to the highest rate of sulfolane loss in synthetic water samples. Experiments on sulfolane contaminated groundwater samples also indicated that these three combinations can efficiently degrade sulfolane. Furthermore, a synergistic effect was observed in the combination of H2O2 and O3 photolysis. PMID- 27372266 TI - Accumulation of atmospheric radionuclides and heavy metals in cryoconite holes on an Arctic glacier. AB - Surface of glaciers is covered by mineral and organic dust, together with microorganisms forming cryoconite granules. Despite fact that glaciers and ice sheets constitute significance part of land surface, reservoir of freshwater, and sites of high biological production, the knowledge on the cryoconite granules still remain unsatisfactory. This study presents information on radionuclide and heavy metal contents in cryoconites. Cryoconites collected from the Hans Glacier in SW Spitsbergen reveal high activity concentrations of anthropogenic ((238,239,240)Pu, (137)Cs, (90)Sr) and natural ((210)Pb) radionuclides. The (238)Pu/(239+240)Pu activity ratios in these cryoconites significantly exceed the mean global fallout ratio (0.025). The (238)Pu/(239+240)Pu ranged from 0.064 to 0.118. The (239+240)Pu/(137)Cs varied from 0.011 +/- 0.003 to 0.030 +/- 0.007. Such activity ratios as observed in these cryoconites were significantly higher than the values characterizing global fallout, pointing to possible contributions of these radionuclides from other sources. Heavy metals (Pb, Cd, Cu, Zn, Fe, and Mn) in cryoconites exceed both UCC concentrations and local rocks' concentrations, particularly for cadmium. The concentration ratios of stable lead isotopes ((206)Pb/(207)Pb, (208)Pb/(206)Pb) were determined to discriminate between the natural and anthropogenic sources of Pb in cryoconites and to confirm the strong anthropogenic contribution to heavy metal deposition in the Arctic. In investigated cryoconite holes, two groups of invertebrates, both extremophiles, Tardigrada and Rotifera were detected. Our study indicate that cryoconites are aggregates of mineral and organic substances on surfaces of glaciers are able to accumulate large amounts of airborne pollutants bound to extracellular polymeric substances secreted by microorganisms. PMID- 27372267 TI - Partial Epithelial-to-Mesenchymal Transition and Other New Mechanisms of Kidney Fibrosis. AB - Kidney fibrosis is the unavoidable consequence of chronic kidney disease irrespective of the primary underlying insult. It is a complex phenomenon governed by the interplay between different cellular components and intricate networks of signaling pathways, which together lead to loss of renal functionality and replacement of kidney parenchyma with scar tissue. An immense effort has recently been made to understand the molecular and cellular mechanisms leading to kidney fibrosis. The cellular protagonists of this process include myofibroblasts, tubular epithelial cells, endothelial cells, and immune cells. We discuss here the most recent findings, including partial epithelial-to mesenchymal transition (EMT), in the initiation and progression of tissue fibrosis and chronic kidney disease (CKD). A deep understanding of these mechanisms will allow the development of effective therapies. PMID- 27372268 TI - Quantification of cell membrane permeability induced by monopolar and high frequency bipolar bursts of electrical pulses. AB - High-frequency bipolar electric pulses have been shown to mitigate undesirable muscle contraction during irreversible electroporation (IRE) therapy. Here, we evaluate the potential applicability of such pulses for introducing exogenous molecules into cells, such as in electrochemotherapy (ECT). For this purpose we develop a method for calculating the time course of the effective permeability of an electroporated cell membrane based on real-time imaging of propidium transport into single cells that allows a quantitative comparison between different pulsing schemes. We calculate the effective permeability for several pulsed electric field treatments including trains of 100MUs monopolar pulses, conventionally used in IRE and ECT, and pulse trains containing bursts or evenly-spaced 1MUs bipolar pulses. We show that shorter bipolar pulses induce lower effective membrane permeability than longer monopolar pulses with equivalent treatment times. This lower efficiency can be attributed to incomplete membrane charging. Nevertheless, bipolar pulses could be used for increasing the uptake of small molecules into cells more symmetrically, but at the expense of higher applied voltages. These data indicate that high-frequency bipolar bursts of electrical pulses may be designed to electroporate cells as effectively as and more homogeneously than conventional monopolar pulses. PMID- 27372269 TI - Small-for-gestational-age infants among uncomplicated pregnancies at term: a secondary analysis of 9 Maternal-Fetal Medicine Units Network studies. AB - BACKGROUND: Most small (birthweight <10%) for-gestational-age cases occur at term, in uncomplicated pregnancies, and are not identified during prenatal visits as having fetal growth restriction. Hence, they do not benefit from antepartum surveillance and timed delivery. There is dismissive and disquieting opinion that small for gestational age among uncomplicated pregnancies is not associated with increased morbidities and, therefore, does not warrant improved detection. Our hypothesis was that among uncomplicated pregnancies at term, small for gestational age have significantly higher morbidity and mortality than appropriate (birthweight 10-89%) for gestational age. OBJECTIVE: We sought to compare composite neonatal morbidity among uncomplicated term singleton pregnancies with small vs appropriate for gestational age. STUDY DESIGN: We culled collected data from 9 completed Maternal-Fetal Medicine Units studies conducted from 1989 through 2004. All data were collected prospectively by trained staff. We excluded women who delivered <37 weeks and those with hypertension or diabetes, multiple gestation, known anomalies, and birthweight of >=90% for gestational age. Using multivariable analysis, we compared composite neonatal morbidity, which included stillbirth and neonatal mortality between small and appropriate for gestational age. Random effect logistic regressions were used to account for study heterogeneity, with adjustment for potential confounders. We calculated adjusted odds ratios and 95% confidence intervals. RESULTS: Of the >91,000 women enrolled in the studies, 60% (n = 50,011) met the inclusion criteria. Among the uncomplicated pregnancies, 10.8% (n = 5416) were small for gestational age. The rate of composite neonatal morbidity of 16% in small for gestational age and 10% in appropriate for gestational age persisted (adjusted odds ratio, 1.75; 95% confidence interval, 1.71-1.78). After adjustment for confounders, the following neonatal morbidities were significantly more common among term small than appropriate for gestational age: Apgar <4 at 5 minutes, respiratory distress syndrome, mechanical ventilation, necrotizing enterocolitis grade 2 or 3, and neonatal sepsis. Lastly, rate of stillbirths (3.5 vs 0.9/1000 births; adjusted odds ratio, 3.49; 95% confidence interval, 1.83 6.67) and neonatal mortality (1.1 vs 0.4/1000 births; adjusted odds ratio, 2.56; 95% confidence interval, 1.83-3.57) were significantly more common with small than appropriate for gestational age. In secondary analyses the composite neonatal morbidity among newborns at <5% and at 5-9% was significantly higher than appropriate for gestational age. Lastly, in subgroup analyses of women who delivered at 37.0-38.6 weeks or at >=39.0 weeks, the increased rate of composite neonatal morbidity, stillbirth, and neonatal mortality among small for gestational age persisted. CONCLUSION: Among uncomplicated pregnancies at term, small- compared to appropriate-for-gestational-age newborns have a significantly higher likelihood of composite neonatal morbidity, stillbirth, and neonatal mortality. A large multicenter trial is warranted to determine if improved detection of small for gestational age among uncomplicated pregnancies can mitigate morbidities and mortality, without disproportionate interventions and iatrogenic complications. PMID- 27372270 TI - Proposed diagnostic criteria for the case definition of amniotic fluid embolism in research studies. AB - Amniotic fluid embolism is a leading cause of maternal mortality in developed countries. Our understanding of risk factors, diagnosis, treatment, and prognosis is hampered by a lack of uniform clinical case definition; neither histologic nor laboratory findings have been identified unique to this condition. Amniotic fluid embolism is often overdiagnosed in critically ill peripartum women, particularly when an element of coagulopathy is involved. Previously proposed case definitions for amniotic fluid embolism are nonspecific, and when viewed through the eyes of individuals with experience in critical care obstetrics, would include women with a number of medical conditions much more common than amniotic fluid embolism. We convened a working group under the auspices of a committee of the Society for Maternal-Fetal Medicine and the Amniotic Fluid Embolism Foundation whose task was to develop uniform diagnostic criteria for the research reporting of amniotic fluid embolism. These criteria rely on the presence of the classic triad of hemodynamic and respiratory compromise accompanied by strictly defined disseminated intravascular coagulopathy. It is anticipated that limiting research reports involving amniotic fluid embolism to women who meet these criteria will enhance the validity of published data and assist in the identification of risk factors, effective treatments, and possibly useful biomarkers for this condition. A registry has been established in conjunction with the Perinatal Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development to collect both clinical information and laboratory specimens of women with suspected amniotic fluid embolism in the hopes of identifying unique biomarkers of this condition. PMID- 27372271 TI - Using Interdisciplinary Workgroups to Educate Surgery Residents in Systems-Based Practice. AB - BACKGROUND: Meaningful education of residents in systems-based practice is notoriously challenging, despite its recognition as 1 of the 6 Accreditation Council for Graduate Medical Education core competencies. To address this challenge, surgery residents and other members of the health care team were organized into interdisciplinary workgroups that were tasked with developing solutions to "systems issues" confronted on a daily basis. The project's goals included providing more meaningful, hands-on educational experience for residents in system-based practice, while also generating practical solutions to workflow issues through interprofessional collaboration. PROJECT DESIGN: Project participants included all surgery residents at the University of Virginia in Charlottesville, VA, as well as surgical health care professionals across all disciplines. Participants were organized into workgroups. Over the course of 3 sessions, each of 1-hour, each workgroup identified commonly encountered systems issues, chose 1 issue to address, and determined an implementable solution for this issue. In total, 140 participants were divided among 13 workgroups. PROJECT EXECUTION: Workgroup topics ranged from improving paging etiquette to standardizing interdisciplinary communication. In total, 9 of the 13 proposals have been piloted or fully implemented as standard practice at our institution, either within a single unit or over the entire health system. DISCUSSION: This project demonstrates an innovative approach toward resident education in system based practice, providing residents with a hands-on experience in problem solving from a systems perspective. These interdisciplinary workgroups generated effective solutions to issues that were meaningful to frontline health care providers. Interdisciplinary collaboration within the workgroups served as a valuable team-building exercise to improve relations between the disciplines. This project can serve as a model for other institutions desiring meaningful education in the Accreditation Council for Graduate Medical Education competency of systems-based practice. PMID- 27372272 TI - Exploring Senior Residents' Intraoperative Error Management Strategies: A Potential Measure of Performance Improvement. AB - OBJECTIVE: The study aim was to determine whether residents' error management strategies changed across 2 simulated laparoscopic ventral hernia (LVH) repair procedures after receiving feedback on their initial performance. We hypothesize that error detection and recovery strategies would improve during the second procedure without hands-on practice. DESIGN: Retrospective review of participant procedural performances of simulated laparoscopic ventral herniorrhaphy. A total of 3 investigators reviewed procedure videos to identify surgical errors. Errors were deconstructed. Error management events were noted, including error identification and recovery. SETTING: Residents performed the simulated LVH procedures during a course on advanced laparoscopy. Participants had 30 minutes to complete a LVH procedure. After verbal and simulator feedback, residents returned 24 hours later to perform a different, more difficult simulated LVH repair. PARTICIPANTS: Senior (N = 7; postgraduate year 4-5) residents in attendance at the course participated in this study. RESULTS: In the first LVH procedure, residents committed 121 errors (M = 17.14, standard deviation = 4.38). Although the number of errors increased to 146 (M = 20.86, standard deviation = 6.15) during the second procedure, residents progressed further in the second procedure. There was no significant difference in the number of errors committed for both procedures, but errors shifted to the late stage of the second procedure. Residents changed the error types that they attempted to recover (chi25=24.96, p<0.001). For the second procedure, recovery attempts increased for action and procedure errors, but decreased for strategy errors. Residents also recovered the most errors in the late stage of the second procedure (p < 0.001). CONCLUSION: Residents' error management strategies changed between procedures following verbal feedback on their initial performance and feedback from the simulator. Errors and recovery attempts shifted to later steps during the second procedure. This may reflect residents' error management success in the earlier stages, which allowed further progression in the second simulation. Incorporating error recognition and management opportunities into surgical training could help track residents' learning curve and provide detailed, structured feedback on technical and decision-making skills. PMID- 27372273 TI - iPAD or PADi-'tablets' with therapeutic disease potential? AB - Over the last five years, a growing body of literature has strengthened the rationale for the involvement of PAD (protein arginine deiminase) enzymes in diverse diseases, through direct roles of citrullination in mechanisms such as neutrophil extracellular trap formation and immune complex formation. The recent development of inhibitors of the PAD family, coupled with the availability of mice genetically deficient in PAD2 or PAD4, has accelerated understanding of the role of these targets in varied disease models. This review surveys the recent literature to confirm the therapeutic potential of PAD inhibitors as a new class of drugs to treat human autoimmune disease. PMID- 27372274 TI - Prevalence, knowledge and attitudes relating to beta-alanine use among professional footballers. AB - OBJECTIVES: To investigate beta-alanine supplementation use and level of knowledge amongst professional footballers. DESIGN: Cross-sectional survey of Australian professional football players. METHODS: Questionnaires assessing beta alanine supplementation behaviours, level of knowledge and sources of information were completed by professional rugby union (RU) (n=87), rugby league (RL) (n=180) and Australian Rules Football (ARF) (n=303) players. RESULTS: Approximately 61% of athletes reported beta-alanine use, however use by ARF football players (44%) was lower than that of RU (80%) and RL players (80%). The majority of respondents were not using beta-alanine in accordance with recommendations. Only 35% of the participants were able to correctly identify the potential benefits of beta alanine supplementation. The main information sources that influenced players' decision to use beta-alanine were strength and conditioning coach (71%) and dietitian (52%). Forty-eight per cent of athletes never read labels prior to supplementing and only 11% completed their own research on beta-alanine. Compared to RL and ARF players, RU players had both a greater knowledge of beta-alanine supplementation and better supplementation practices. CONCLUSIONS: Despite over half the surveyed professional footballers using beta-alanine, the majority of athletes used beta-alanine in a manner inconsistent with recommendations. A better understanding of the environment and culture within professional football codes is required before supplement use becomes consistent with evidence based supplement recommendations. PMID- 27372275 TI - Field evaluation of a random forest activity classifier for wrist-worn accelerometer data. AB - OBJECTIVES: Wrist-worn accelerometers are convenient to wear and associated with greater wear-time compliance. Previous work has generally relied on choreographed activity trials to train and test classification models. However, validity in free-living contexts is starting to emerge. Study aims were: (1) train and test a random forest activity classifier for wrist accelerometer data; and (2) determine if models trained on laboratory data perform well under free-living conditions. DESIGN: Twenty-one participants (mean age=27.6+/-6.2) completed seven lab-based activity trials and a 24h free-living trial (N=16). METHODS: Participants wore a GENEActiv monitor on the non-dominant wrist. Classification models recognising four activity classes (sedentary, stationary+, walking, and running) were trained using time and frequency domain features extracted from 10-s non-overlapping windows. Model performance was evaluated using leave-one-out-cross-validation. Models were implemented using the randomForest package within R. Classifier accuracy during the 24h free living trial was evaluated by calculating agreement with concurrently worn activPAL monitors. RESULTS: Overall classification accuracy for the random forest algorithm was 92.7%. Recognition accuracy for sedentary, stationary+, walking, and running was 80.1%, 95.7%, 91.7%, and 93.7%, respectively for the laboratory protocol. Agreement with the activPAL data (stepping vs. non-stepping) during the 24h free-living trial was excellent and, on average, exceeded 90%. The ICC for stepping time was 0.92 (95% CI=0.75-0.97). However, sensitivity and positive predictive values were modest. Mean bias was 10.3min/d (95% LOA=-46.0 to 25.4min/d). CONCLUSIONS: The random forest classifier for wrist accelerometer data yielded accurate group-level predictions under controlled conditions, but was less accurate at identifying stepping verse non stepping behaviour in free living conditions Future studies should conduct more rigorous field-based evaluations using observation as a criterion measure. PMID- 27372276 TI - Perceived barriers to leisure-time physical activity during pregnancy: A literature review of quantitative and qualitative evidence. AB - OBJECTIVES: Identify perceived barriers to leisure-time physical activity during pregnancy to inform future interventions aimed at improving physical activity levels in pregnancy. DESIGN: PubMed/Medline and Web of Science databases were systematically searched using a reference period between 1986 and January/2016. METHODS: A comprehensive search strategy was developed combining the following keywords: (barriers OR constraints OR perceptions OR attitudes) AND (physical activity OR exercise OR motor activity) AND (pregnancy OR pregnant women OR antenatal OR prenatal). Thematic synthesis was conducted to analyze the data. A socioecological model was used to categorize the reported barriers. RESULTS: Twelve quantitative studies and 14 qualitative studies were included. Barriers belonging to the intrapersonal level of the socioecological model were the most reported in the studies and were categorized in five themes as follows: (1) Pregnancy-related symptoms and limitations; (2) Time constraints; (3) Perceptions of already being active, (4) Lack of motivation and (5) Mother-child safety concerns. At the interpersonal level, barriers were coded into two descriptive themes: (1) Lack of advice and information and (2) Lack of social support. Two other themes were used to summarize Environmental, Organizational and Policy barriers: (1) Adverse weather and (2) Lack of resources. CONCLUSIONS: A range of relevant barriers to leisure-time physical-activity engagement during pregnancy were identified in this literature review. Pregnancy-related symptoms and limitations barriers were the most reported in studies, regardless of study design. Mother-child safety concerns, lack of advice/information and lack of social support were also important emphasized pregnancy-related barriers to be targeted in future interventions. PMID- 27372277 TI - Acclimation improves salt stress tolerance in Zea mays plants. AB - Plants exposure to low level salinity activates an array of processes leading to an improvement of plant stress tolerance. Although the beneficial effect of acclimation was demonstrated in many herbaceous species, underlying mechanisms behind this phenomenon remain poorly understood. In the present study we have addressed this issue by investigating ionic mechanisms underlying the process of plant acclimation to salinity stress in Zea mays. Effect of acclimation were examined in two parallel sets of experiments: a growth experiment for agronomic assessments, sap analysis, stomatal conductance, chlorophyll content, and confocal laser scanning imaging; and a lab experiment for in vivo ion flux measurements from root tissues. Being exposed to salinity, acclimated plants (1) retain more K(+) but accumulate less Na(+) in roots; (2) have better vacuolar Na(+) sequestration ability in leaves and thus are capable of accumulating larger amounts of Na(+) in the shoot without having any detrimental effect on leaf photochemistry; and (3) rely more on Na(+) for osmotic adjustment in the shoot. At the same time, acclimation affect was not related in increased root Na(+) exclusion ability. It appears that even in a such salt-sensitive species as maize, Na(+) exclusion from uptake is of a much less importance compared with the efficient vacuolar Na(+) sequestration in the shoot. PMID- 27372278 TI - Generation of poly-beta-hydroxybutyrate from acetate in higher plants: Detection of acetoacetyl CoA reductase- and PHB synthase- activities in rice. AB - It has been reported that Poly-beta-hydroxybutyrate (PHB) is generated from acetate in the rice root. However, no information is available about the biosynthetic pathway of PHB from acetate in plant cells. In the bacterium Ralstonia eutropha H16 (R. eutropha), PHB is synthesized from acetyl CoA by the consecutive reaction of three enzymes: beta-ketothiolase (EC: 2.3.1.9), acetoacetyl CoA reductase (EC: 1.1.1.36) and PHB synthase (EC: 2.3.1.-). Thus, in this study, we examined whether the above three enzymatic activities were also detected in rice seedlings. The results clearly showed that the activities of the above three enzymes were all detected in rice. In particular, the PHB synthase activity was detected specifically in the sonicated particulate fractions (2000g 10min precipitate (ppt) and the 8000g 30min ppt) of rice roots and leaves. In addition to these enzyme activities, several new experimental results were obtained on PHB synthesis in higher plants: (a) (14)C-PHB generated from 2-(14)C acetate was mainly localized in the 2000g 10min ppt and the 8000g 30min ppt of rice root. (b) Addition of acetate (0.1-10mM) to culture medium of rice seedlings did not increase the content of PHB in the rice root or leaf. (c) In addition to C3 plants, PHB was generated from acetate in a C4 plant (corn) and in a CAM plant (Bryophyllum pinnatum). d) Washing with ethylenediaminetetraacetic acid (EDTA) strongly suggested that the PHB synthesized from acetate was of plant origin and was not bacterial contamination. PMID- 27372279 TI - Does a pre-intervention functional assessment increase intervention effectiveness? A meta-analysis of within-subject interrupted time-series studies. AB - This study examined the relative effectiveness of interventions based on a pre intervention functional behavioral assessment (FBA), compared to interventions not based on a pre-intervention FBA. We examined 19 studies that included a direct comparison between the effects of FBA- and non-FBA-based interventions with the same participants. A random effects meta-analysis of effect sizes indicated that FBA-based interventions were associated with large reductions in problem behaviors when using non-FBA-based interventions as a reference intervention (Effect size=0.85, 95% CI [0.42, 1.27], p<0.001). In addition, non FBA based interventions had no effect on problem behavior when compared to no intervention (0.06, 95% CI [-0.21, 0.33], p=0.664). Interestingly, both FBA-based and non-FBA-based interventions had significant effects on appropriate behavior relative to no intervention, albeit the overall effect size was much larger for FBA-based interventions (FBA-based: 1.27, 95% CI [0.89, 1.66], p<0.001 vs. non FBA-based: 0.35, 95% CI [0.14, 0.56], p=0.001). In spite of the evidence in favor of FBA-based interventions, the limited number of comparative studies with high methodological standards underlines the need for further comparisons of FBA-based versus non-FBA-based interventions. PMID- 27372280 TI - Characterization of hemorrhages in the tenderloins of slaughter pigs. AB - Muscle hemorrhages are regularly observed in especially the tip of the tenderloin muscles of slaughter pigs. In order to characterize the hemorrhages, a macro- and microscopic examination of tenderloins with (n=5) and without (n=4) hemorrhages and the associated vertebral column was carried out. Furthermore, all columns were radiographed and two were CT scanned. Histologically, the muscle hemorrhages contained cells from bone marrow and growth line cartilage. Ventral epiphysiolysis in either the cranial or caudal epiphysis of the first lumbar vertebrae (L1) in 8 out of the 9 vertebral columns was present. In the 5 cases with tenderloin hemorrhage, similar hemorrhage with growth line cartilage was found within the fracture of the epiphysis. The hemorrhages develop secondarily to epiphysiolysis in the lumbar vertebrae, where the tenderloin attaches to the spine. The lesions probably develop around the time of stunning. PMID- 27372281 TI - Utilization of retroperitoneal lymph node dissection for testicular cancer in the United States: Results from the National Cancer Database (1998-2011). AB - INTRODUCTION: Retroperitoneal lymph node dissection (RPLND) for the treatment of testicular cancer is a relatively rare and complex operation that may contribute to differences in utilization. We sought to characterize the use of RPLND between different categories of cancer center facilities in the United States. MATERIALS AND METHODS: The National Cancer Database was queried for patients with germ cell tumors treated at different types of cancer centers between 1998 and 2011. The proportion of patients who underwent RPLND was stratified by stage and histology and then compared between treatment facilities. RPLND utilization was then compared between facility types as a function of time. RESULTS: A total of 59,652 patients met inclusion criteria and 5,475 (9.2%) underwent RPLND. The proportion of patients treated with RPLND for non-seminomatous germ cell tumor (NSGCT) was significantly different between cancer center types for all stages (P<0.001) and used most often in academic comprehensive cancer centers. There was no difference in the proportion of RPLND utilization for stage II and III seminoma stratified by treatment facility. There was a significantly decreased trend in the utilization of RPLND for stage I (P = 0.032) NSGCT whereas utilization was increased for stage III NSGCT (P<=0.001) over the study period. CONCLUSIONS: The proportion of patients undergoing RPLND for NSGCT varies significantly by the type of cancer center and is used most often in academic cancer centers. Utilization of RPLND decreased for stage I NSGCT and increased for stage III NSGCTs during the study period. PMID- 27372282 TI - Determinants of radical cystectomy operative time. AB - OBJECTIVE: To examine factors associated with radical cystectomy operative time among Medicare beneficiaries. MATERIAL AND METHODS: Using linked Surveillance, Epidemiology, and End Results-Medicare data, we identified 4,975 patients who underwent a radical cystectomy during 1991 to 2007. Using a validated method of using anesthesia administrative data to quantify operative time, we used generalized estimating equations to examine the association of patient, provider, and hospital factors on radical cystectomy operative time. RESULTS: We found that mean operative time decreased by 5 minutes per year (Delta = -5.3min/y, P<0.001). Longer operative times were found in academic centers (Delta =+39.0min vs. nonacademic), continent diversion (Delta =+34.9min vs. ileal conduit), surgical excision of>=11 lymph nodes (Delta =+24.9min vs. 1-5), female (Delta =+32.3min vs. male sex), and perioperative anesthesia procedures such as placement of central venous catheters or arterial lines (Delta =+47.2min vs. no procedures), respectively (all P<0.01). In adjusted analysis, higher surgeon volume (Delta = 22.0min vs. lowest volume) was associated with shorter operative times (P = 0.002). CONCLUSIONS: Operative times for cystectomy have been steadily decreasing annually. There is notable variation based on academic affiliation, diversion type and extent of lymphadenectomy, surgeon and hospital volumes, as well as use of anesthetic procedures. Efforts to improve operative time by selective referral to high-volume surgeons or hospitals or both, or judicious use of perioperative procedures may have a positive effect on health care costs and overall quality of care for patients undergoing radical cystectomy for bladder cancer. PMID- 27372283 TI - Calibrated kallikrein generation in human plasma. AB - OBJECTIVES: The physiological role of the contact system remains inconclusive. No obvious clinical complications have been observed for factor XII (FXII), prekallikrein (PK), or high molecular weight kininogen deficiencies even though the contact system in vitro is associated with coagulation, fibrinolysis, and inflammation. A global generation assay measuring the initial phase of the contact system could be a valuable tool for studies of its physiological role. DESIGN AND METHODS: We investigated whether such a method could be developed using the principle of the Calibrated Automated Thrombin generation method as a template. RESULTS: A suitable kallikrein specific fluorogenic substrate was identified (KM=0.91mM, kcat=19s-1), and kallikrein generation could be measured in undiluted plasma when silica was added as activator. Disturbing effects, including substrate depletion and the inner-filter effect, however, affected the signal. These problems were corrected for by external calibration with alpha2 macroglobulin-kallikrein complexes. Selectivity studies of the substrate, experiments with FXII and PK depleted plasmas, and plasma with high or low complement C1-esterase inhibitor activity indicated that the obtained and calibrated signal predominantly was related to FXII-dependent kallikrein activity. CONCLUSIONS: The findings described show that establishment of a kallikrein generation method is possible. Potentially, this setup could be used for clinical studies of the contact system. PMID- 27372284 TI - Experiences from using LC-MS/MS for analysis of immunosuppressive drugs in a TDM service. AB - A liquid chromatography-tandem mass spectrometry method is presented that was applied for over five years for routine measurement of the immunosuppressant drugs ciclosporin, everolimus, sirolimus and tacrolimus in blood. The method has been used for analysis of 142 thousand unknowns and has been running 7days a week without a single day shutdown during the entire time. The measuring ranges were 10-1500ng/mL for ciclosporin and 1-50ng/mL for everolimus, sirolimus and tacrolimus. The method validation showed performance meeting the EMA validation guideline requirements and acceptable performance in a proficiency control program. The routine work was based on daily calibrations on two parallel instrument systems, one with multiplexing providing a capacity of 55 injections/h. During week-days up to six batches of samples were run to meet requirements of short reporting times. Although there is still room for method improvements our main conclusion is that the liquid chromatography-tandem mass spectrometry technique provides a viable platform for an analytical routine service for therapeutic drug monitoring of immunosuppressant drugs that meet clinical needs of reporting times and reliable results. We also describe early involvement and education of clinicians to gain acceptance and correct clinical interpretation of analytical results more accurate and precise, but differing from those obtained by immunoassay. PMID- 27372285 TI - Performance of a phosphoflow assay to determine phosphorylation of S6 ribosomal protein as a pharmacodynamic read out for mTOR inhibition. AB - OBJECTIVES: The S6 ribosomal protein (S6RP) is phosphorylated by the mammalian target of rapamycin (mTOR). The objective of this study was to assess the analytical suitability of a commercial kit-based phosphoflow cytometry protocol using whole blood (WBS) to measure the level of phosphorylated S6RP (p-S6RP) in T cell subsets to study the pharmacodynamic effects of mTOR inhibitors (mTORi). DESIGN AND METHODS: A kit was used for fixation and permeabilization of mitogen stimulated cells, and p-S6RP was assessed separately in CD3+CD4+ and CD3+CD8+ cells by employing an anti-phospho-Ser235/236 antibody. Specificity, linearity, within-run precision and stability were investigated in either WBS spiked with everolimus and non-mTORi immunosuppressants or in WBS from patients on immunosuppressive therapy (n=56). In addition, healthy controls (n=10) and patients without immunosuppression (n=10) were included. A comparison (n=15) with an established western blot method based on anti-phospho p70S6 kinase (Thr389) was made by splitting WBS. RESULTS: Everolimus decreased p-S6RP in vitro concentration dependently (0.00-27.4MUg/L). This effect was also confirmed in vivo after a single dose of everolimus to healthy volunteers (n=3). However, spiking WBS with 500MUg/L cyclosporine also decreased p-S6RP. The within-run coefficient of variation was <18% in transplant patients and <27% in healthy controls for both cell subsets. Sample stability for p-S6RP analysis was limited (<24h). p-S6RP was significantly decreased in CD3+CD8+ cells of patients treated with sirolimus (p=0.02) but not with everolimus. No significant correlation between the phosphoflow- and western blot method was noted. CONCLUSION: The phosphoflow assay of p-S6RP performed well analytically, but sample stability, specificity, and method comparison results question its fitness for clinical purposes. PMID- 27372286 TI - Imaging of hypoxia in mouse atherosclerotic plaques with (64)Cu-ATSM. AB - INTRODUCTION: Cardiovascular disease is the leading cause of death in the United States. The identification of vulnerable plaque at risk of rupture has been a major focus of research. Hypoxia has been identified as a potential factor in the formation of vulnerable plaque, and it is clear that decreased oxygen plays a role in the development of plaque angiogenesis leading to plaque destabilization. The purpose of this study is to demonstrate the feasibility of copper-64 labeled diacetyl-bis (N(4)-methylthiosemicarbazone) ((64)Cu-ATSM), a positron-emitting radiopharmaceutical taken up in low-oxygen-tension cells, for the identification of hypoxic and potentially unstable atherosclerotic plaque in a mouse model. METHODS: (64)Cu-ATSM PET was performed in 21 atherosclerotic apolipoprotein E knockout (ApoE(-/-)) mice, 6 of which were fed high-fat diet (HFD) while the others received standard-chow diet (SCD), and 13 control wild type mice fed SCD. 4 SCD ApoE(-/-) mice and 4 SCD wild type mice also underwent (18)F fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) imaging one day prior to (64)Cu-ATSM PET. RESULTS: (64)Cu-ATSM uptake was increased in the aortic arch in SCD ApoE(-/-) mice (average aortic arch/muscle (A/M) standardized uptake value ratio 7.5-30min post injection: (5.66+/-0.23) compared to control mice (A/M SUV ratio 7.5-30min post injection (3.87+/-0.22), p<0.0001). HFD ApoE(-/-) mice also showed similarly increased aortic arch uptake on PET imaging in comparison to control mice. Immunohistochemistry in both HFD and SCD ApoE(-/-) mice revealed noticeable hypoxia by pimonidazole stain in atherosclerosis which was co localized to macrophage by CD68 staining. Autoradiography assessment demonstrated the presence of hypoxia by (64)Cu-ATSM uptake correlated with pimonidazole uptake within the ex vivo atherosclerotic aortic arch specimens. A significant increase in (18)F-FDG uptake in the SCD ApoE(-/-) mice in comparison to controls was also observed at delayed time points. CONCLUSION: This pre-clinical study suggests that (64)Cu-ATSM is a potential PET tracer for hypoxia imaging in atherosclerosis. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: While studies in humans are necessary for conclusive data, in the long term, a (64)Cu ATSM PET imaging strategy could help facilitate the study of plaque biology in human patients. PMID- 27372287 TI - Synthesis and antiproliferative activity of a natural like glycoconjugate polycyclic compound. AB - A natural like O-glycoconjugate polycyclic compound 4 was obtained by a multistep procedure starting from N-(3-methyl-1-(4-nitrophenyl)-1H-pyrazol-5-yl)acetamide. The glycosyl derivative 4 showed antiproliferative activity against all the tumoral cell lines of the NCI panel in the range 0.47-5.43 MUM. Cytofluorimetric analysis performed on MDA-MB231, a very aggressive breast cancer cell line, which does not express estrogen, progesterone and HER-2/neu receptors, showed that 4 is able to induce prolonged cell cycle arrest at G2/M phase and morphological signs of differentiation. These events are correlated with down-regulation of both cyclin B1 and cdc2, the cyclins involved in G2/M transition, as well as up regulation of cyclin-dependent kinase (CDK) inhibitor p21 Cip1/Waf1. PMID- 27372288 TI - Design, synthesis and biological evaluation of 4-anilinoquinazoline derivatives as new c-myc G-quadruplex ligands. AB - A series of 4-anilinoquinazoline derivatives were designed and synthesized as novel c-myc promoter G-quadruplex binding ligands. Subsequent biophysical and biochemical evaluation demonstrated that the introduction of aniline group at 4 position of quinazoline ring and two side chains with terminal amino group improved their binding affinity and stabilizing ability to G-quadruplex DNA. RT PCR assay and Western blot showed that compound 7a could down-regulate transcription and expression of c-myc gene in Hela cells, which was consistent with the behavior of an effective G-quadruplex ligand targeting c-myc oncogene. More importantly, RTCA and colony formation assays indicated that 7a obviously inhibited Hela cells proliferation, without influence on normal primary cultured mouse mesangial cells. Flow cytometric assays suggested that 7a induced Hela cells to arrest in G0/G1 phase both in a time-dependent and dose-dependent manner. PMID- 27372289 TI - Dietary Interventions and Irritable Bowel Syndrome: A Review of the Evidence. AB - Irritable bowel syndrome (IBS) is the best studied of the functional gastrointestinal disorders. It is a highly prevalent disorder characterized by symptoms of abdominal pain, bloating, and disordered bowel habits, which may include constipation, diarrhea, or both. IBS has a significant negative impact on patients, both financially and with regard to their quality-of-life. At present, there is no cure for IBS, and while there are a number of pharmacological therapies available to treat IBS symptoms, they are not uniformly effective. For this reason, many patients and providers are turning to dietary interventions in an attempt to ameliorate IBS symptoms. At first glance, this approach appears reasonable as dietary interventions are generally safe and side effects, including potential adverse reactions with medications, are rare. However, although dietary interventions for IBS are frequently recommended, there is a paucity of data to support their use. The goals of this article are to answer key questions about diets currently recommended for the treatment of IBS, using the best available data from the literature. PMID- 27372290 TI - Endoscopic Management of Gallbladder Stones: Can We Eliminate Cholecystectomy? AB - The gold standard for the management of acute cholecystitis is laparoscopic cholecystectomy. In patients that are not fit for surgery, percutaneous cholecystostomy is the standard treatment. However, the procedure is only a temporary measure for controlling gallbladder symptoms and it is frequently associated with morbidities. Recently, endoscopic options for management of acute cholecystitis have been developed. The approach avoids the need for a percutaneous drain and may allow endoscopic treatment of the gallstone. The aim of this article is to provide an overview on the current status of endoscopic management of acute cholecystitis. PMID- 27372291 TI - Sarcopenia in Patients with Chronic Liver Disease: Can It Be Altered by Diet and Exercise? AB - Sarcopenia, a loss of muscle mass, is being increasingly recognized to have a deleterious effect on outcomes in patients with chronic liver disease. Factors related to diet and the inflammatory nature of chronic liver disease contribute to the occurrence of sarcopenia in these patients. Sarcopenia adversely influences quality of life, performance, morbidity, success of transplantation, and even mortality. Specific deficiencies in macronutrients (protein, polyunsaturated fatty acids) and micronutrients (vitamins C, D, and E, carotenoids, and selenium) have been linked to sarcopenia. Lessons learned from nutritional therapy in geriatric patient populations may provide strategies to manage sarcopenia in patients with liver disease. Combining diet modification and nutrient supplementation with an organized program of exercise may help ameliorate or even reverse the effects of sarcopenia on an already complex disease process. PMID- 27372292 TI - Determinants of cancer screening in Asian-Americans. AB - PURPOSE: Recent data suggest that Asian-Americans (AsAs) are more likely to present with advanced disease when diagnosed with cancer. We sought to determine whether AsAs are under-utilizing recommended cancer screening. METHODS: Cross sectional analysis of the 2012 Behavioral Risk Factor Surveillance System comprising of AsAs and non-Hispanic White (NHW) community-dwelling individuals (English and Spanish speaking) eligible for colorectal, breast, cervical, or prostate cancer screening according to the United States Preventive Services Task Force recommendations. Age, education and income level, residence location, marital status, health insurance, regular access to healthcare provider, and screening were extracted. Complex samples logistic regression models quantified the effect of race on odds of undergoing appropriate screening. Data were analyzed in 2015. RESULTS: Weighted samples of 63.3, 33.3, 47.9, and 30.3 million individuals eligible for colorectal, breast, cervical, and prostate cancer screening identified, respectively. In general, AsAs were more educated, more often married, had higher levels of income, and lived in urban/suburban residencies as compared to NHWs (all p < 0.05). In multivariable analyses, AsAs had lower odds of undergoing colorectal (odds ratio [OR] 0.78, 95 % confidence interval [CI] 0.63-0.96), cervical (OR 0.45, 95 % CI 0.36-0.55), and prostate cancer (OR 0.55, 95 % CI 0.39-0.78) screening and similar odds of undergoing breast cancer (OR 1.29, 95 % CI 0.92-1.82) screening as compared to NHWs. CONCLUSIONS: AsAs are less likely to undergo appropriate screening for colorectal, cervical, and prostate cancer. Contributing reasons include limitations in healthcare access, differing cultural beliefs on cancer screening and treatment, and potential physician biases. Interventions such as increasing healthcare access and literacy may improve screening rates. PMID- 27372293 TI - Systematic review of the use of granulocyte-macrophage colony-stimulating factor in patients with advanced melanoma. AB - Several immunomodulatory checkpoint inhibitors have been approved for the treatment of patients with advanced melanoma, including ipilimumab, nivolumab and pembrolizumab. Talimogene laherparepvec is the first oncolytic virus to gain regulatory approval in the USA; it is also approved in Europe. Talimogene laherparepvec expresses granulocyte-macrophage colony-stimulating factor (GM CSF), and with other GM-CSF-expressing oncolytic viruses in development, understanding the clinical relevance of this cytokine in treating advanced melanoma is important. Results of trials of GM-CSF in melanoma have been mixed, and while GM-CSF has the potential to promote anti-tumor responses, some preclinical data suggest that GM-CSF may sometimes promote tumor growth. GM-CSF has not been approved as a melanoma treatment. We undertook a systematic literature review of studies of GM-CSF in patients with advanced melanoma (stage IIIB-IV). Of the 503 articles identified, 26 studies met the eligibility criteria. Most studies investigated the use of GM-CSF in combination with another treatment, such as peptide vaccines or chemotherapy, or as an adjuvant to surgery. Some clinical benefit was reported in patients who received GM-CSF as an adjuvant to surgery, or in combination with other treatments. In general, outcomes for patients receiving peptide vaccines were not improved with the addition of GM-CSF. GM-CSF may be a valuable therapeutic adjuvant; however, further studies are needed, particularly head-to-head comparisons, to confirm the optimal dosing regimen and clinical effectiveness in patients with advanced melanoma. PMID- 27372295 TI - When Acute Respiratory Distress Syndrome is not ARDS. PMID- 27372294 TI - Association of Single Nucleotide Polymorphisms of PADI4 and HLA-DRB1 Alleles with Susceptibility to Rheumatoid Arthritis-Related Lung Diseases. AB - OBJECTIVE: Lung diseases (LD) are common extra-articular manifestations in rheumatoid arthritis (RA). However, little is known about factors associated with susceptibility to rheumatoid arthritis-related lung diseases (RA-LD). The aim of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) of PADI4 and HLA-DRB1 alleles were associated with RA-LD. METHODS: Blood samples and clinical data were collected from 116 consecutive RA patients who satisfied the 1987 American College of Rheumatology classification criteria. RA LD was diagnosed using high-resolution computed tomography of the chest. All patients were genotyped for SNPs of PADI4 and HLA-DRB1 alleles and analyzed for full amino acid sequence of the HLA protein corresponding to a 4-digit HLA typing. Data were analyzed by independent t test (or Mann-Whitney test) for continuous variables, Chi-square test (or Fisher's exact test) and trend test for categorical variables, and logistic regression analysis. RESULTS: Ninety-four (81.0 %) RA patients had LD, of which eight (6.9 %) had interstitial lung disease (ILD) and 92 (79.3 %) had airway abnormalities in which 64 (55.2 %) showed bronchiectasis and 47 (40.5 %) revealed bronchial wall thickening. The recessive genotype of padi4_92 was susceptible to airway abnormalities (OR = 2.22, 95 % CI = 1.05-4.49, p = 0.034). Tryptophan at position 9 of HLA-DRB1 sequence was associated with the susceptibility to RA-ILD (OR = 22.89, 95 % CI = 1.20-432.56, p = 0.037). CONCLUSION: PADI4 polymorphisms and HLA-DRB1 alleles could attribute differently to the development of airway abnormalities and ILD, respectively, in RA. PMID- 27372296 TI - Anorectal malformations associated spinal cord anomalies. AB - PURPOSE: The present study aims to identify clinical and pathological factors that can predict the risk of spinal cord anomalies (SCA) in patients with anorectal malformations (ARM), the need for neurosurgery, and to define the impact of SCA on the outcome of patients with ARM. METHODS: A 16-year retrospective analysis of all patients treated at a single tertiary children's Hospital with diagnosis of ARM. Data were collected to assess the impact of defined clinical characteristics on prevalence of SCA (detected at MRI). Children surgically treated or not for SCA were compared for age, clinical symptoms and type of anomalies at surgery or at last follow-up, respectively. Moreover, patients with intermediate/high ARMs, with or without SCA were compared for neurogenic bladder (NB), constipation, soiling and need for bowel management (BM). RESULTS: Two hundred and seventy-five children were treated for ARM in the study period, 142 had spinal MRI that showed SCA in 85. Patients with SCA had significantly higher prevalence of preterm birth (p < 0.05), cardiac anomalies (p = 0.02), vertebral anomalies (p = 0.0075), abnormal sacrum (p < 0.0001), and VACTERL association (p = 0.0233). Ten patients were surgically treated for SCA. The prevalence of neurological bladder and neuro-motor deficits, of vertebral and genital anomalies, particularly cryptorchidism, was significantly higher in the operated group (p < 0.01, for each analysis). In patients with intermediate/high ARMs, no significant difference was observed between those with or without SCA, in terms of prevalence of NB, intestinal function and need for BM. CONCLUSIONS: In patients with ARM, factors that can predict a higher prevalence of SCA and also determine an increased indication to neurosurgery may be identified. SCA by itself does not seem to affect the functional prognosis of children with intermediate/high ARM. These data may help physicians in stratifying the clinical and diagnostic pathway of patients with ARM. PMID- 27372297 TI - Novel use of porcine urinary bladder matrix for pediatric pilonidal wound care: preliminary experience. AB - BACKGROUND: Extracellular matrix is used in various applications. We present our preliminary experience using a new device that consists of a porcine extracellular matrix with an epithelial basement membrane (MatriStem((r)), ACell, Inc. Columbia, MD, USA) for adolescent pilonidal disease. METHODS: A retrospective review of four patients with pilonidal disease was undertaken. Three occurred in the gluteal cleft, and the fourth in the umbilicus. In the first patient, the wound deficit was filled with lyophilized MicroMatrix powder and a sheet of Multilayer Wound Matrix was placed to cover the wound. In the second patient, two sinus tracts were debrided, packed with MicroMatrix, and a sheet of fenestrated Burn Matrix was applied. In the third patient, MicroMatrix and Surgical Matrix PSMX (six-layer) was applied as a roll filling the dead space. In the last patient, an umbilical sinus 3 cm deep was packed with MicroMatrix powder followed by a rolled sheet of 2-ply Surgical Matrix RS. Patients were evaluated weekly post-operatively, and more MicroMatrix and sheet material was added if a wound deficit was still present. Measurements were taken in two dimensions, diameter and depth, to characterize wounds. RESULTS: Resolution of wound deficit was graphed versus time. Pain was assessed by scoring 0-10. Rapid wound closure was achieved. Two of the patients had failed wound healing with saline dressing changes prior to MatriStem application. These two patients in particular were highly satisfied with the comfort of the MatriStem approach relative to their time with saline dressings. Most had no pain after 1 week when bolster sutures were removed. CONCLUSION: In the treatment of open pilonidal wounds in adolescents, porcine urinary bladder matrix wound care devices offer closure times and cost similar to well-established methods while offering a substantial advantage in terms of patient comfort and convenience. This preliminary experience supports a prospective study. PMID- 27372298 TI - Primary sigmoidectomy and appendicostomy for chronic idiopathic constipation. AB - PURPOSE: To present our experience in patients with chronic idiopathic constipation complicated by megarectosigmoid and fecal incontinence who underwent a primary sigmoidectomy and appendicostomy. METHODS: We reviewed eight patients referred to the Colorectal Center from 2014 to 2016 with chronic idiopathic constipation and undergoing a sigmoidectomy and appendicostomy. We analyzed the previous medical treatment, indications for the surgical procedure, and outcomes. RESULTS: Age at operation was 5-19 years. Time with constipation was 4-15 years. All patients received multiple laxatives, mainly polyethylene glycol, and all had severe social problems. Four patients have autism. The indication for surgery was an unsuccessful laxative trial, refusal to continue with rectal enemas or both, and social fear of continued fecal incontinence. Post-operatively, all patients were having daily bowel movements without fecal accidents. CONCLUSION: Selected patients with chronic idiopathic constipation complicated by megarectosigmoid and fecal incontinence can obtain great benefit from primary sigmoidectomy and appendicostomy. PMID- 27372299 TI - Subcutaneous trigeminal nerve field stimulation for refractory trigeminal pain: a cohort analysis. AB - BACKGROUND: Neurosurgical pain management of drug-resistant trigeminal neuralgia (TN) is highly challenging. Microvascular decompression is a first-line neurosurgical approach for classical TN with neurovascular conflict, but can show clinical relapse despite proper decompression. Second-line destructive techniques like radiofrequency thermocoagulation have become reluctantly used due to their potential for irreversible side effects. Subcutaneous peripheral nerve field stimulation (sPNFS) is a minimally invasive neuromodulatory technique which has been shown to be effective for chronic localised pain conditions. Reports on sPNFS for the treatment of trigeminal pain (sTNFS) are still sparse and primarily focused on pain intensity as outcome measure. Detailed data on the impact of sTNFS on attack frequency are currently not available. METHODS: Patients were classified according to the International Headache Society classification (ICHD-3 beta). Three patients had classical TN without (n = 3) and another three TN with concomitant persistent facial pain (n = 3). Two patients suffered from post herpetic trigeminal neuropathy (n = 2). All eight patients underwent a trial stimulation of at least 7 days with subcutaneous leads in the affected trigeminal area connected to an external neurostimulator. Of those, six patients received permanent implantation of a neurostimulator. During the follow-up (6-29 months, mean 15.2), VAS-scores, attack frequencies, oral drug intake, complications and side effects were documented. RESULTS: Seven out of eight patients responded to sTNFS (i.e. >=50 % pain reduction) during the test trial. The pain intensity (according to VAS) was reduced by 83 +/- 16 % (mean +/- SD) and the number of attacks decreased by 73 +/- 26 % (mean +/- SD). Five out of six patients were able to reduce or stop pain medication. One patient developed device infection. Two patients developed stimulation-related side effects which could be resolved by reprogramming. CONCLUSIONS: Treatment by sTNFS is a beneficial option for patients with refractory trigeminal pain. Prospective randomised trials are required to systematically evaluate efficacy rates and safety of this low invasive neurosurgical technique. PMID- 27372300 TI - Evidence of an excessive gender gap in the risk of psychotic disorder among North African immigrants in Europe: a systematic review and meta-analysis. AB - PURPOSE: Epidemiological studies in the Netherlands have reported an excessive gender gap in the risk for non-affective psychotic disorder (NAPD) among immigrants from Morocco with a higher risk elevation in males compared to females. We examined the consistency of these findings and their generalizability to immigrants from the Maghreb (Mauritania, Morocco, Algeria, Tunisia and Libya) in other European countries. METHODS: Systematic review and meta-analysis. Medline, PsychINFO and EMBASE databases were searched for publications in the period from January 1970 to April 2014. We included incidence and prevalence studies of non-affective psychotic disorder (NAPD) among migrants from the Maghreb in Europe and studies of subclinical psychotic symptoms (SPS) in representative samples. A meta-analysis was performed on the subgroup of incidence studies. RESULTS: Five incidence and three prevalence studies of NAPD, and two prevalence studies of SPS, conducted in the Netherlands (n=7), Belgium (n=1), France (n=1) and Italy (n=1) met our inclusion criteria. Across all research designs, the risks of NAPD and SPS were consistently increased among male, not female immigrants from the Maghreb. The meta-analysis of incidence studies of NAPD yielded male-to-female risk ratios of 5.1 [95 % confidence interval (CI) 3.1-8.4] for migrants from the Maghreb, 2.0 (95 % CI 1.6-2.5) for other migrant groups, and 1.8 (95 % CI 1.3-2.5) for non-migrant Europeans. CONCLUSIONS: The marked gender gap in psychosis risk among migrants from the Maghreb appears a consistent finding, foremost among the Moroccan-Dutch. The small number of studies limits the strength of conclusions that can be drawn about countries other than the Netherlands. Achievement-expectation mismatch, social marginalization and an increased prevalence of illicit drug use are possible explanations. PMID- 27372301 TI - Sex differences in the relationships between body dissatisfaction, quality of life and psychological distress. AB - BACKGROUND: Body dissatisfaction is associated with impairment in women's quality of life (QoL). To date, research has not examined the relationship between body dissatisfaction and men's QoL, or sex differences in this relationship. METHODS: A community sample of 966 males and 1,031 females living in Australia provided information about their body dissatisfaction, mental health and physical health related QoL, and eating disorder symptoms. Data were analysed using three hierarchical multiple regressions and interactions between body dissatisfaction and sex were examined. RESULTS: For both sexes, increasing levels of body dissatisfaction were associated with poorer mental and physical health-related QoL and greater psychological distress. The adverse associations between body dissatisfaction and mental health-related QoL, and between body dissatisfaction and psychological distress, were more pronounced for males. CONCLUSION: High levels of body dissatisfaction may threaten the psychological and physical wellbeing of both men and women. Body dissatisfaction appears to be a public health problem, distinct from the eating disorders and other adverse psychological phenomena for which body dissatisfaction is commonly discussed as a risk factor. Males, historically understudied and underrepresented in body image research, warrant increased empirical attention. PMID- 27372303 TI - Genomic Landscape of poorly Differentiated and Anaplastic Thyroid Carcinoma. AB - Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are aggressive thyroid tumors associated with a high mortality rate of 38 57 % and almost 100 % respectively. Several recent studies utilizing next generation sequencing techniques have shed lights on the molecular pathogenesis of these tumors, providing evidence to support a stepwise tumoral progression from well-differentiated to poorly differentiated, and finally to anaplastic thyroid carcinomas. While BRAF (V600E) and RAS mutations remain the main drivers in aggressive thyroid carcinoma, PDTC and ATC gains additional mutations, e.g., TERT promoter mutation, TP53 mutation, as well as frequent alterations in PIK3CA PTEN-AKT-mTOR pathway, SWI-SNF complex, histomethyltransferases, and mismatch repair genes. RAS-mutated PDTCs are commonly associated with a histologic phenotype defined by Turin proposal, high frequency of distant metastasis, high thyroid differentiation score, and a RAS-like gene expression profile, whereas BRAF-mutated PDTCs are usually defined solely by the Memorial Sloan Kettering Cancer Center (MSKCC) criteria with a propensity for nodal metastasis and are less differentiated with a BRAF-like expression signature. Such demarcation is largely lost in ATC which is characterized by genomic complexity, heavy mutation burden, and profound undifferentiation. Additionally, several molecular events, e.g., EIF1AX mutation, mutation burden, and chromosome 1q gain in PDTCs, as well as EIF1AX mutation, chromosome 13q loss, and 20q gains in ATCs, may serve as adverse prognostic markers predicting poor clinical outcome. PMID- 27372304 TI - Blastobotrys (Arxula) adeninivorans: a promising alternative yeast for biotechnology and basic research. AB - Blastobotrys adeninivorans (syn. Arxula adeninivorans) is a non-conventional, non pathogenic, imperfect, haploid yeast, belonging to the subphylum Saccharomycotina, which has to date received comparatively little attention from researchers. It possesses unusual properties such as thermo- and osmotolerance, and a broad substrate spectrum. Depending on the cultivation temperature B. (A.) adeninivorans exhibits different morphological forms and various post translational modifications and protein expression properties that are strongly correlated with the morphology. The genome has been completely sequenced and, in addition, there is a well-developed transformation/expression platform, which makes rapid, simple gene manipulations possible. This yeast species is a very good host for homologous and heterologous gene expression and is also a useful gene donor. Blastobotrys (A.) adeninivorans is able to use a very wide range of substrates as carbon and/or nitrogen sources and is an interesting organism owing to the presence of many metabolic pathways, for example degradation of n-butanol, purines and tannin. In addition, its unusual properties and robustness make it a useful bio-component for whole cell biosensors. There are currently a number of products on the market produced by B. (A.) adeninivorans and further investigation may contribute further innovative solutions for current challenges that exist in the biotechnology industry. Additionally it may become a useful alternative to existing commercial yeast strains and as a model organism in research. In this review we present information relevant to the exploitation of B. (A.) adeninivorans in research and industrial settings. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27372306 TI - [Not Available]. PMID- 27372302 TI - Influence of metabolic syndrome on upper gastrointestinal disease. AB - A recent increase in the rate of obesity as a result of insufficient physical exercise and excess food consumption has been seen in both developed and developing countries throughout the world. Additionally, the recent increased number of obese individuals with lifestyle-related diseases associated with abnormalities in glucose metabolism, dyslipidemia, and hypertension, defined as metabolic syndrome (MS), has been problematic. Although MS has been highlighted as a risk factor for ischemic heart disease and arteriosclerotic diseases, it was also recently shown to be associated with digestive system disorders, including upper gastrointestinal diseases. Unlike high body weight and high body mass index, abdominal obesity with visceral fat accumulation is implicated in the onset of various digestive system diseases because excessive visceral fat accumulation may cause an increase in intra-abdominal pressure, inducing the release of various bioactive substances, known as adipocytokines, including tumor necrosis factor-alpha, interleukin-6, resistin, leptin, and adiponectin. This review article focuses on upper gastrointestinal disorders and their association with MS, including obesity, visceral fat accumulation, and the major upper gastrointestinal diseases. PMID- 27372305 TI - The development and validation of a new survey tool: the first step to profiling New Zealanders' eating styles and moving patterns. PMID- 27372307 TI - [Not Available]. PMID- 27372309 TI - [Not Available]. PMID- 27372308 TI - [Not Available]. PMID- 27372310 TI - [Not Available]. PMID- 27372311 TI - [Not Available]. PMID- 27372313 TI - [Not Available]. PMID- 27372314 TI - [Not Available]. PMID- 27372315 TI - [Not Available]. PMID- 27372312 TI - Antipsychotic Drug-Induced Somnolence: Incidence, Mechanisms, and Management. AB - Somnolence is a common side effect of antipsychotics. To assess the incidence of this side effect, we performed a MEDLINE search for randomized, double-blinded, placebo- or active-controlled studies of adult patients treated with antipsychotics for schizophrenia, mania, bipolar depression, or bipolar disorder. We extracted rates of somnolence from original publications and pooled them based on the dose of each antipsychotic in the same psychiatric condition, then estimated the absolute risk increase (ARI) and the number needed to harm (NNH) of an antipsychotic relative to placebo or an active comparator in the same psychiatric condition. According to the ARI in acute schizophrenia, bipolar mania, and bipolar depression, antipsychotics can be classified as high somnolence (clozapine), moderate somnolence (olanzapine, perphenazine, quetiapine, risperidone, ziprasidone), and low somnolence (aripiprazole, asenapine, haloperidol, lurasidone, paliperidone, cariprazine). The risk of somnolence with blonanserin, brexpiprazole, chlorpromazine, iloperidone, sertindole, and zotepine needs further investigation. The rates of somnolence were positively correlated to dose and duration for some antipsychotics, but not for others. Many factors, including antipsychotic per se, the method used to measure somnolence, patient population, study design, and dosing schedule, might affect the incidence of antipsychotic-induced somnolence. The mechanisms of antipsychotic-induced somnolence are likely multifactorial, although the blockade of histamine 1 receptors and alpha1 receptors may play a major role. The management of antipsychotic-induced somnolence should include sleep hygiene education, choosing an antipsychotic with a lower risk for somnolence, starting at a lower dose with a slower titration based on psychiatric diagnoses, adjusting doses when necessary, and minimizing concurrent somnolence-prone agents. Since most cases of somnolence were mild to moderate, allowing tolerance to develop over at least 4 weeks is reasonable before discontinuing an antipsychotic. PMID- 27372316 TI - [Not Available]. PMID- 27372318 TI - [Not Available]. PMID- 27372317 TI - [Not Available]. PMID- 27372319 TI - [Not Available]. PMID- 27372320 TI - [Not Available]. PMID- 27372321 TI - [Not Available]. PMID- 27372322 TI - [Not Available]. PMID- 27372323 TI - [Not Available]. PMID- 27372324 TI - [Not Available]. PMID- 27372325 TI - [Not Available]. PMID- 27372326 TI - [Not Available]. PMID- 27372327 TI - [Not Available]. PMID- 27372328 TI - [Not Available]. PMID- 27372329 TI - [Not Available]. PMID- 27372331 TI - [Not Available]. PMID- 27372330 TI - [Not Available]. PMID- 27372332 TI - [Not Available]. PMID- 27372333 TI - [Not Available]. PMID- 27372334 TI - [Not Available]. PMID- 27372335 TI - [Not Available]. PMID- 27372338 TI - [Not Available]. PMID- 27372336 TI - A seed-based cross-modal comparison of brain connectivity measures. AB - Human neuroimaging methods have provided a number of means by which the connectivity structure of the human brain can be inferred. For instance, correlations in blood-oxygen-level-dependent (BOLD) signal time series are commonly used to make inferences about "functional connectivity." Correlations across samples in structural morphometric measures, such as voxel-based morphometry (VBM) or cortical thickness (CT), have also been used to estimate connectivity, putatively through mutually trophic effects on connected brain areas. In this study, we have compared seed-based connectivity estimates obtained from four common correlational approaches: resting-state functional connectivity (RS-fMRI), meta-analytic connectivity modeling (MACM), VBM correlations, and CT correlations. We found that the two functional approaches (RS-fMRI and MACM) had the best agreement. While the two structural approaches (CT and VBM) had better than-random convergence, they were no more similar to each other than to the functional approaches. The degree of correspondence between modalities varied considerably across seed regions, and also depended on the threshold applied to the connectivity distribution. These results demonstrate some degrees of similarity between connectivity inferred from structural and functional covariances, particularly for the most robust functionally connected regions (e.g., the default mode network). However, they also caution that these measures likely capture very different aspects of brain structure and function. PMID- 27372337 TI - Axon diameter relates to synaptic bouton size: structural properties define computationally different types of cortical connections in primates. AB - Neural connections are implemented by axons of different diameters, whose spectrum increases depending on species and areas. Axon diameter determines conduction velocity and is proportional to the size of the cell body of origin. We describe that in motor, callosal connections of the monkey thick axons distribute larger boutons than thin axons, suggesting that faster axons also release more neurotransmitter at their termination, probably activating more powerfully their targets. PMID- 27372339 TI - [Not Available]. PMID- 27372340 TI - [Not Available]. PMID- 27372341 TI - [Not Available]. PMID- 27372342 TI - [Not Available]. PMID- 27372343 TI - [Not Available]. PMID- 27372345 TI - [Not Available]. PMID- 27372344 TI - [Not Available]. PMID- 27372347 TI - [Not Available]. PMID- 27372346 TI - [Not Available]. PMID- 27372348 TI - Treatment of adult and pediatric high-grade gliomas with Withaferin A: antitumor mechanisms and future perspectives. AB - Resistance mechanisms employed by high-grade gliomas allow them to successfully evade current standard treatment of chemotherapy and radiation treatment. Withaferin A (WA), utilized in Ayurvedic medicine for centuries, is attracting attention for its antitumor capabilities. Here we review pertinent literature on WA as a high-grade glioma treatment, and discuss the cancerous mechanisms it affects. WA is relatively nontoxic and has shown potential in crossing the blood brain barrier. WA prevents p53 alterations and inactivates overexpressed MDM2 through ARF and ROS production. Furthermore, WA upregulates Bax, inducing mitochondrial death cascades, inhibits mutated Akt, mTOR, and NF-kappaB pathways, and inhibits angiogenesis in tumors. Therapy with WA for high-grade gliomas is supported through the literature. Further investigation is warranted and encouraged to fully unearth its abilities against malignant gliomas. PMID- 27372349 TI - Ferulic acid ameliorates chronic constriction injury induced painful neuropathy in rats. AB - OBJECTIVE: This study focuses on the evaluation of phenolic compound ferulic acid (FA, 4-hydroxy-3-methoxycinnamic acid) in the chronic constriction injury (CCI) of sciatic nerve induced neuropathy in rats. METHODS: Thirty-six animals were randomly divided into six groups. Left sciatic nerve was exposed and ligated, animals in the control, standard, and test groups were treated orally with respective drugs for 21 days. Nociceptive thresholds (THERMAL hyperalgesia, mechanical hyperalgesia, and tactile allodynia) were assessed at 0 days and thereafter every 3 days till 3 weeks. Three weeks later, the sciatic nerve tissue homogenate was prepared and subjected for estimation of oxidative markers namely total protein, nitric oxide, lipid peroxidase, interleukins (IL-1beta and IL-6). RESULTS: Pregabalin (10 mg/kg, p.o.) and ferulic acid (10, 20, 30 mg/kg, p.o.), significantly and dose dependently, decreased all nociceptive thresholds (thermal hyperalgesia, mechanical hyperalgesia, and tactile allodynia) and biochemical markers (total protein, nitric oxide, lipid peroxidase, and interleukins). CONCLUSION: In conclusion, the anti-hyperalgesic effect of FA in rats receiving CCI might partly be attributed to its anti-oxidant and anti-inflammatory activity and is associated with the maintenance of neuropathic pain and could be useful as an adjuvant to conventional medicines. PMID- 27372350 TI - Effect of sphingosine-1-phosphate on L-type calcium current and Ca(2+) transient in rat ventricular myocytes. AB - Modulation of Ca(2+) homoeostasis in cardiac myocytes plays a major role in beat to-beat regulation of heart function. Previous studies suggest that sphingosine-1 phosphate (S1P), a biologically active sphingomyelin metabolite, regulates Ca(2+) handling in cardiac myocytes, but the underlying mechanism is unclear. In the present study, we tested the hypothesis that S1P-induced functional alteration of intracellular Ca(2+) handling includes the L-type calcium channel current (ICa,L) via a signalling pathway involving P21-activated kinase 1 (Pak1). Our results show that, in rat ventricular myocytes, S1P (100 nM) does not affect the basal activity of ICa,L but is able to partially reverse the effect of the beta adrenergic agonist Isoproterenol (ISO, 100 nM) on ICa,L. S1P (25 nM) also significantly prevents ISO (5 nM)-induced Ca(2+) waves and diastolic Ca(2+) release in these cells. Our further molecular characterisation demonstrates that Pak1 activity is increased in myocytes treated with S1P (25 nM) compared with those myocytes without treatment of S1P. By immunoprecipitation we demonstrate that Pak1 and protein phosphatase 2A (PP2A) are associated in ventricular tissue indicating their functional interaction. Thus the results indicate that S1P attenuates beta-adrenergic stress-induced alteration of intracellular Ca(2+) release and L-type Ca(2+) channel current at least in part via Pak1-PP2A-mediated signalling. PMID- 27372351 TI - Treatment with Parkinsonia aculeata combats insulin resistance-induced oxidative stress through the increase in PPARgamma/CuZn-SOD axis expression in diet-induced obesity mice. AB - Parkinsonia aculeata L. (Caesalpiniaceae) is a traditional ethnomedicine and has been used for the empiric treatment of hyperglycemia, without scientific background. Mechanistic analyses at molecular level from the antioxidant mechanism observed by P. aculeata are required. Herein the effects of the treatment by hydroethanolic extract partitioned with ethyl acetate of P. aculeata aerial parts (HEPa/EtOAc) in mice fed a high-fat diet that share many obesity phenotypes with humans were evaluated. The animals were treated orally with HEPa/EtOAc (125 and 250 mg/kg/day) and pioglitazone (5 mg/kg/day), for 16 days. After the treatment, HEPa/EtOAc reduced fasting serum glucose and insulin levels, as well as homeostasis model assessment for insulin resistance. In addition, an improvement in glucose intolerance was also observed. Indeed, a reduction in the circulating levels of TNF-alpha and IL-6 was also observed. Furthermore, at molecular level, it was demonstrated that the HEPa/EtOAc treatment was able to improve these physiological parameters, through the activation of peroxisome proliferator-activated receptor gamma (PPARgamma) per si, as well as the enhancement of antioxidant mechanism by an increase in PPARgamma/Cu(2+), Zn(2+) superoxide dismutase (CuZn-SOD) axis expression in liver and adipose tissue. In sum, P. aculeata is effective to improve insulin resistance in a mouse model of obesity and this effect seems to involve the antioxidant and anti-inflammatory mechanisms through the increase in PPARgamma/CuZn-SOD axis expression. PMID- 27372352 TI - Go in! Go out! Inducible control of nuclear localization. AB - Cells have evolved a variety of mechanisms to regulate the enormous complexity of processes taking place inside them. One mechanism consists in tightly controlling the localization of macromolecules, keeping them away from their place of action until needed. Since a large fraction of the cellular response to external stimuli is mediated by gene expression, it is not surprising that transcriptional regulators are often subject to stimulus-induced nuclear import or export. Here we review recent methods in chemical biology and optogenetics for controlling the nuclear localization of proteins of interest inside living cells. These methods allow researchers to regulate protein activity with exquisite spatiotemporal control, and open up new possibilities for studying the roles of proteins in a broad array of cellular processes and biological functions. PMID- 27372353 TI - [Are schizophrenic patients being told their diagnosis today in France?] AB - INTRODUCTION: The progressive shifts in the legal and social contexts, along with major changes in information seeking habits with the development of the Internet, have placed patients' information at the core of medical practice. This has to be applied to the psychiatric fields as well, and to questions about how schizophrenic patients are being told their diagnosis nowadays in France. METHODS: This paper is a national and international literature review about schizophrenia diagnosis disclosure practices, from 1972 to 2014, using French and English languages and various psychology and medical databases. The used key words were "diagnosis", "disclosure", "communication", "breaking bad news", "information", "schizophrenia" and "psychosis". RESULTS: Proportions of diagnosis announcement: our results show that the proportion of psychiatrists delivering schizophrenia diagnosis to their patients varies between countries. Although we must acknowledge that the questionnaires and samples are diverse, we have found that psychiatrists are in general less prone to deliver diagnosis information in France (from 13,5% to 39% given the studies), Germany (28%), Italy (30%), and Japan (30%), than in Anglo-Saxon countries. Thus, 70% of the psychiatrists in North America and 56% in Australia claim that they disclose their diagnosis to schizophrenic patients. In the United-Kingdom, a study targeting psychotic patients themselves has shown that 47% of them had been told their diagnosis by their doctor. Even in the countries where the proportion of diagnosis disclosure is the highest, there remains a substantial difference with other mental illnesses such as affective or anxiety disorders, which are almost always labeled as such in the information communicated to the patient (90% in North America). Diagnostic information about schizophrenia continues therefore to appear problematic for health professionals, which can seem a paradox given the recent social and legal evolutions, the therapeutic progress, the proved benefits of disclosure on compliance and therapeutic alliance, and the fact that numerous studies have shown that a majority of patients already know their diagnosis having discovered it on the Internet or by reading their treatments' notice. Reasons alleged for not disclosing diagnosis: the reasons alleged by psychiatrists for not disclosing diagnosis are various, including fear of aggravating the stigma and the emotional state of the patient, fear of giving a wrong diagnosis, fear of suicidal behavior, risk of misunderstanding, low level of patient's insight, absence of therapeutic advantage, or absence of request from the patient. Evolution of the French position about diagnosis disclosure: The publication of the relatively large study of Bayle et al. in 1999, as well as the patients' rights evolutions, has led to a debate among psychiatrists about the reasons alleged in France for not disclosing diagnosis. Among other explanations, it appeared that the theoretical reference of the psychiatrist plays a role, a psychoanalytic practice leading to increased reluctance in breaking the bad news. Thus, the psychiatrist's view of the disease, in terms of etiology and prognosis, is important as the diagnosis could become accusing if the psychiatrist believes the family environment played a role, or harmful if he has a pessimistic conception of prognosis. The question of stigma: among other reasons alleged by psychiatrists for not announcing the diagnosis, the fear of causing an increased stigma is frequently reported by professionals. In France, stigma about schizophrenia is high, not only among the general population but also among health practitioners. Even if the context has evolved during the past 30 years and the therapeutic efficiency has improved, French representations of schizophrenia remain often tinted with catastrophism and should be modified. Benefits of diagnosis disclosure: however, the benefits of disclosing diagnosis have been constantly proved in France as in other environments. Several studies have shown that patients knowing their diagnosis were likely to develop a better compliance and a stronger therapeutic alliance with their doctor. No aggravation of symptoms, suicidal risk or anxiety has been linked to the diagnosis disclosure. On the contrary, the relief of being able to put some words on symptoms, better recognize them and anticipate them, and be part of a group of patients sharing the same symptomatology has been described by patients. Furthermore, disclosing a schizophrenia diagnosis can be essential to the psychotherapeutic project, in the sense that it places the patient into an active role towards the disease and the care plan. Last but not least, the relatives can benefit from the disclosure as well and build a partnership with health professionals about medical care. Existing recommendations: in the French context, apart from individual recommendations produced by a few authors in the literature, there are no official specific recommendations about how to disclose a difficult diagnosis in the psychiatric field; only recommendations concerning severe chronic somatic disease are available. The complexity of the schizophrenia diagnosis disclosure has led some researchers - especially in North America and Australia - to adapt and use in the context of schizophrenia protocols, recommendations and even communication skills training programs that have been developed in oncology or in the field of severe chronic somatic disease. DISCUSSION: For the situation to evolve in France, tools able to measure patients' consent - including consent to hear the bad news - ability could be used. The question of how much information and what kind of information the patients really wish should therefore be explored in deep. Also, we have seen that schizophrenia representations should be modified in the general public understanding as well as in the professional environment. Families should be more included in the reflection about diagnosis announcement, as psycho-education programs have shown their efficiency and usefulness for both patients and relatives. Finally, in order to overcome some of the difficulties related to breaking the bad news about a schizophrenia diagnosis, developing the existing Anglo-Saxon models and recommendations in France, where only very few protocols exist, could allow a positive evolution in clinical practice and help to set a therapeutic and partnering approach of diagnosis disclosure. However, in order to better understand the situation in France regarding schizophrenia diagnosis disclosure, the present state of clinical practice still remains to be analyzed precisely, as the last study on a relatively large sample was made only in 1999. Thus, the obvious limits of our study lie in the fact that most available surveys in France are not recent enough to have taken into account legal and social evolutions. Also, the studies that we used for this paper use different methodologies, in the majority focus solely on health professionals, and they are not representative enough in terms of size or sample to inform about the present state of the practice. CONCLUSION: As a conclusion, having stressed the lack of recent data about schizophrenia diagnosis disclosure in France, we suggest a new study using validated tools on a representative sample and taking into account both perceptions of psychiatrist and patient. As has been the case for other severe pathologies, we also suggest that a consensus conference take place on the subject of schizophrenia diagnostic information in order to elaborate guidelines to support this difficult disclosure. PMID- 27372354 TI - [Out of addictions: Alcohol, or alcohol to alcohol]. AB - : Pathways from alcoholism to recovery are documented; less often are those from drug addiction to alcoholism. Biographical approaches allow analyzing how people change their uses and talk about their trajectories of recovery. METHODS: Three hundred and forty-one people (34% women) in the Paris area were questioned on their trajectories with a biographical questionnaire. Some open questions were aimed to understand the connection they made between events in their lives, how recovered they felt and what they considered strengths or obstacles. All the participants had stopped at least one product. Their mean age was 43, and 26% were over 50. STUDY OBJECTIVES: How can the differences between one substance addicts and dual abusers be explained? Can we hypothesize a better result for the patients with a single dependence to alcohol in their lives for the following two reasons? (1) They could really be taken in charge for their alcoholism whereas the dual abusers mostly receive cared for their illicit drug problems with an under estimation of their problem with alcohol. In this case, they turn to alcohol after weaning themselves from their drug dependence so as to return to a social consumption, especially when they are given an opiate treatment. (2) Conversely could we suggest that the dual substance abusers had different trajectories from their childhood (more adverse events, more social difficulties, mental health problems), and that this accumulation explains their skipping from one substance or behaviour to another without any real recovery for decades? RESULTS: All respondents were polydrug users. Eighty-two had been dependent mainly on alcohol. One hundred and twenty-one people had been drug addicts (mostly heroin), which they had stopped on average ten years before the survey. The last group included 138 persons who had been heroin or cocaine addicts and alcoholics in their lives, a third of whom had been dependent on alcohol before their drug addiction (35%), a tenth on both at the same time (10%) and more than half of the users (55%) had turned from drug addiction to alcoholism. The group concerning alcohol dependence includes the oldest participants, on average 49.7, and 55% of them were abstinent at the survey. Conversely, the group "with no alcohol dependence" had mainly turned to opiate treatments. Their histories in dependence and in various social statuses also showed a longer duration out of employment, in sickness or invalidity, or in prison, for the drug dependents as opposed to the "mainly" alcoholics. The population with dual substance abuse experienced twice as many adverse childhood events as the others (P<0.005): it was the case for 19.5% in "mainly alcohol" dependence compared to 38.4% in dual abuse. The recovery capital gave a mean score of 7.56+/-2.35 (median 7). A score below 6 was considered low. The score was significantly different according to the dependence groups: while 7.3% of "mainly alcohol" dependents had a score below 6, this was the case for 30.4% of the dual group (with alcohol and drugs), and 19% for the "mainly drug dependence" group. Controlling ages, sexes and groups of dependence in a logistic regression, the risk of having a recovery capital below six was more than four times higher for the dual dependents as opposed to the "mainly alcohol" dependents. CONCLUSION: Some people stay for decades in drug addiction centers switching from one dependence to another. Their alcohol drinking should be addressed earlier to prevent them from turning to drinking excessively in order to wean themselves from their drug addiction. PMID- 27372355 TI - The impact of the neurodevelopmental traction technique on activation of lateral abdominal muscles in children aged 11-13 years. AB - BACKGROUND: The aim of the study was to evaluate the activation of lateral abdominal muscles (LAM) in response to neurodevelopmental traction technique as assessed by ultrasounds as well as to compare the effects of different traction forces. OBJECTIVE: An experiment with repeated measurements of the dependent variables was conducted. Thirty-seven children (22 girls) participated. METHODS: Measurements of LAM thickness (indicating LAM activation) were performed bilaterally during traction of 5% body weight: 1) in neutral position, 2) in 20 degrees posterior trunk inclination; during traction of 15% body weight: 3) in neutral position, 4) in 20 degrees posterior trunk inclination. The ultrasound technology was employed. RESULTS: When applying the lighter traction the superficial LAM (external and internal oblique muscles) showed significant changes. The mean thickness of both muscles during traction increased (both p < 0.001). The deepest transversus abdominis showed no response (p > 0.05). Stronger traction elicited smaller changes. External and internal oblique muscles showed significant increases (p < 0.001, p < 0.01, respectively). Transversus abdominis became less thick during stronger traction (p < 0.01). CONCUSIONS: The neurodevelopmental traction technique elicits the changes in LAM thickness in children with typical development. The superficial LAM show more distinct responses than the profound LAM. Stronger traction induces smaller LAM thickness changes than lighter traction. PMID- 27372356 TI - Functional assessment of immediate task planning and execution by adults with acquired brain injury. AB - BACKGROUND: Individuals with acquired brain injury (ABI) often struggle planning and executing tasks outside daily routines. Given the pervasive effects executive functioning challenges have on independent living, professionals need methods of assessing these skills. OBJECTIVE: This study's purpose was to evaluate an ecologically-valid procedure to assess novel task planning and execution by adults with ABI. METHODS: The researchers implemented a single group design across two phases. Participants included nine adults with severe ABI. In the first experimental phase, participants created a plan for executing tasks that required adherence to pre-determined rules; in the second phase, participants executed the tasks. The researchers tallied information units recorded during the planning phase, performed momentary time-sampling to document observations about participant behaviors, and collected speed, accuracy, and rule violation data about task completion. RESULTS: Planning strategies implemented by most participants were limited to word-for-word copying of some or all of the specified tasks. On average, participants attempted and accurately performed less than half the required tasks and exhibited high rule violation rates. CONCLUSIONS: Given further development and refinement, the implemented procedures may serve as a basis for developing an ecologically-valid tool for evaluating executive functioning in adults with ABI. PMID- 27372357 TI - The effectiveness of psychological interventions for aggressive behavior following acquired brain injury: A meta-analysis and systematic review. AB - BACKGROUND: The consequences of aggressive behavior following ABI have an impact at both an individual and systemic level. In contrast to other ABI sequelae, aggressive behavior has been shown to increase over time without appropriate timely interventions. OBJECTIVE: The current meta-analysis aimed to systematically review the current literature examining psychological interventions for aggressive behavior following ABI. The meta-analysis also aimed to provide a statistical synthesis of the available evidence. METHOD: Following the PRISMA guidelines, an electronic and ancestral search of the available literature identified eleven studies (N = 123) that met the inclusion criteria for the review. Non-overlap effect sizes (Tau-U) were calculated to synthesize the available evidence from single case experimental design studies (SCEDs; N = 7). Standardized mean difference effect sizes (d) were calculated to synthesize the available evidence from group studies (N = 4). RESULTS: A medium omnibus effect size (weighted d = -0.46, 95% CI: -0.69 <> -0.24) was found for group studies. Similarly, the overall effect size (Tau-U) for SCEDs was -0.59 (95% CI: 0.72 <> -0.46), indicating a 59% reduction in aggressive behaviour compared to baseline. CONCLUSION: The findings of the meta-analysis suggest that psychological interventions for aggressive behavior are at least moderately effective at reducing aggressive behavior following ABI. PMID- 27372358 TI - Coping and adaptive strategies of traumatic brain injury survivors and primary caregivers. AB - BACKGROUND: Qualitative research methods allowed the investigator to contribute to the development of new theories and to examine change in processes over time, which added rich detail to existing knowledge of the use of coping and adaptive strategies by traumatic brain injury survivors and their primary caregivers (Ponsford, Sloan, & Snow, 2013). The advantages of phenomenological study were that it allows flexibility to explore and understand meanings attached by people to well-studied concepts such as coping, resiliency, and adaptation or compensation. Phenomenological study was sensitive to contextual factors. It also permitted the study of in-depth dynamics of coping and adaptive strategies of TBI survivors and primary caregivers, while understanding the social and psychological implications of the phenomenon. OBJECTIVE: To explore the needs and deficits of adult traumatic brain injury (TBI) survivors and primary caregivers; and to identify their self-initiated coping and adaptive strategies. Significant to this study was the development of coping and adaptive strategies by the participants after their discharge from inpatient and rehabilitation treatment. The compensatory skills taught in treatment settings did not transfer to the home environment. Therefore, these strategies developed independently from previous treatment recommendations contributed to the development of theory related to rehabilitation and counseling. Distinctive to this study was the similarity of coping and adaptive strategies developed from both mild and severe traumatic brain injury survivors. METHODS: This study consisted of eleven with TBI and six primary caregivers (N = 17), who participated in a series of semi-structured interviews aimed at discovering the coping and adaptive strategies utilized in dealing with the effects of brain injury. A Qualitative Phenomenological design was employed. RESULTS: Patience and understanding, support, and professional help were identified by TBI survivors and caregivers as being their most relevant needs. Self-reported deficits included short-term memory loss (STM), fatigue, anger, and personality changes, and the strategies that TBI survivors and caregivers identified tended to address their problems with these specific day-to day deficits. Problem focused, emotion focused, and avoidant coping were utilized to some degree in their adjustment to home life and activities of daily living. Participants offered suggestions for mental health professionals addressing how to more effectively work with brain injury survivors and their primary caregivers. CONCLUSION: TBI survivors and caregivers had multiple self-reported unaddressed needs following their discharge from facility-based treatment. They reported spontaneously engaging in various coping and adaptive strategies to address their needs and deficits. However, further education regarding potential post-TBI challenges and strategies for addressing them are needed, including a need for community and mental health resources. PMID- 27372359 TI - Driving assessment and rehabilitation using a driving simulator in individuals with traumatic brain injury: A scoping review. AB - BACKGROUND: Due to the heterogeneity of the lesion following a traumatic brain injury (TBI) and the complexity of the driving task, driving assessment and rehabilitation in TBI individuals is challenging. Conventional driving assessment (on-road and in-clinic evaluations) has failed demonstrating effectiveness to assess fitness to drive in TBI individuals. OBJECTIVE: We aimed to determine if driving simulators represent an interesting opportunity in assessing and rehabilitating driving skills in TBI individuals. METHODS: We searched PubMed, CINAHL and Cochrane library databases between 27-02-2014 and 08-04-2014 for articles published since 2000 with the contents of simulator driving assessment and rehabilitation. RESULTS: Out of 488, eight articles with the subject of simulator driving assessment and two with the subject of simulator driving rehabilitation in individuals with TBI were reviewed. CONCLUSIONS: Driving simulators represent a promising avenue for the assessment and rehabilitation of driving skills in TBI individuals as it allows control of stimuli in a safe, challenging and ecologically valid environment and offer the opportunity to measure and record driving performance. Additional studies, however, are needed to document strengths and limitations of this method. PMID- 27372360 TI - Impact of central facial palsy and dysarthria on quality of life in patients with stroke: The KOSCO study. AB - BACKGROUND: There are a few reports on the impact of central facial palsy and dysarthria on quality of life (QOL) in stroke patients. OBJECTIVE: To investigate the impact of central facial palsy on QOL compared with dysarthria during the chronic phase in patients with first-ever strokes. METHODS: This study represents an interim analysis of the Korean Stroke Cohort for Functioning and Rehabilitation study. We selected data from patients with functional independence of 0 or 1 by the modified Rankin Scale at 6 months after stroke onset, who showed an impairment only in National Institute of Health Stroke Scale items 4 (facial palsy) or 10 (dysarthria). Assessments included the European Quality of Life-5 Dimensions (EQ-5D) and the Geriatric depression scale-short form (GDS-SF). RESULTS: Data from 149 patients were selected for this analysis from 3,929 patients who were followed up at 6 months. Thirty-nine and 110 patients were classified into the facial palsy and dysarthria groups, respectively. The groups did not differ significantly in baseline characteristics or functional assessments. EQ-5D was significantly lower in the facial palsy group than in the dysarthria group at 6 months after stroke (p = 0.036). GDS-SF was significantly higher in the facial palsy group than in the dysarthria group (p = 0.005). CONCLUSIONS: The results of this study revealed that central facial palsy clearly has a more negative impact on QOL than dysarthria in chronic stroke patients with functional independence. PMID- 27372361 TI - Action research in rehabilitation with chronic stroke recovery: A case report with a focus on neural plasticity. AB - BACKGROUND: Chronic stroke patients are primarily referred to general rehabilitation, rather than to specific neurorehabilitation. Currently, there are no Danish clinical guidelines for chronic stroke, but recent research in neuroplasticity has contributed to possible rehabilitation interventions for these patients. OBJECTIVE: The purpose of this project is to describe the use of a specialized neuroplastic approach in combination with an already existing training program. METHODS: The project is designed as an action research project concerning four participants with chronic stroke. Through ten intervention, a neuroplastic focus has been added to their group training program including daily home training. Participants were tested before and after the intervention with MAS, DGI, 6MWT, SSQLS. RESULTS: All four participants improved their functional levels and their quality of life following the intervention. CONCLUSIONS: This report indicates that a specific neuroplastic focus in combination with action research has an impact on the participants with chronic stroke. However, there is still no clarity regarding what type of rehabilitation methods can be considered the most efficacious in promoting neuroplasticity. This case report serves as a pilot project for further studies of how to implement neuroplasticity in physical therapy. PMID- 27372362 TI - Swallowing characteristics in Amyotrophic Lateral Sclerosis. AB - BACKGROUND: Motor neurone disease also commonly known as Amyotrophic Lateral Sclerosis (ALS) is a neurological condition which affects various motor functions of the body. Dysphagia (disordered swallowing) is commonly seen in patients with ALS having bulbar symptoms. OBJECTIVES: Research reveals presence of dysphagia in patients with ALS at various stages of swallowing using instrumental assessment. However, very few studies have been done focussing on clinical profiling of swallowing in these patients. Hence, a need was felt to profile the specific characteristics. METHODOLOGY: Five patients diagnosed with ALS were assessed for presence of swallowing disorder using a swallowing checklist which focussed on assessing each stage of swallowing. RESULTS: Results revealed that patients with ALS exhibit difficulties in oral preparatory, oral and pharyngeal stages of swallowing. Inability to hold bolus, reduced mastication, residue in the oral cavity and nasal regurgitation while swallow were observed due to the affected oromotor functions. Swallow reflex was delayed in all the patients. Cough before and during swallow was also observed. CONCLUSION: Dysphagia is a common symptom in patients with ALS and occurs due to the affected oromotor functions. Specific information of the stages of swallowing helps in planning treatment in clinical practice. PMID- 27372363 TI - Walking with a powered robotic exoskeleton: Subjective experience, spasticity and pain in spinal cord injured persons. AB - BACKGROUND: Powered robotic exoskeletons represent an emerging technology for the gait training of Spinal Cord Injured (SCI) persons. The analysis of the psychological and physical impact of such technology on the patient is crucial in terms of clinical appropriateness of such rehabilitation intervention for SCI persons. OBJECTIVE: To investigate the acceptability of overground robot-assisted walking and its effect on pain and spasticity. METHODS: Twenty-one SCI persons participated in a walking session assisted by a powered robotic exoskeleton. Pain assessed using a Numeric Rating Scale (NRS) and muscle spasticity, assessed as subjective perception using an NRS scale and as objective assessment using the Modified Ashworth scale and the Penn scale, were evaluated before and after the walking experience. Positive and negative sensations were investigated using a questionnaire. The patient's global impression of change (PGIC) scale was administrated as well. RESULTS: After the walking session a significant decrease in the muscle spasticity and pain intensity was observed. The SCI persons recruited in this study reported (i) a global change after the walking session, (ii) high scores on the positive and (iii) low scores on the negative sensations, thus indicating a good acceptability of the robot-assisted walking. CONCLUSIONS: The overground robot-assisted walking is well accepted by SCI persons and has positive effects in terms of spasticity and pain reduction. PMID- 27372364 TI - Treadmill training combined with water and land-based exercise programs: Effects on Parkinson's disease patients. AB - BACKGROUND: There is a need for studies about the effects of treadmill training (TT) on Parkinson's disease (PD) patients when combined with other exercise training modalities. OBJECTIVE: To identify the effects of a multicomponent rehabilitation program on the illness impact, quality of life and fitness level in Parkinson's disease. METHODS: Participants were assigned to two exercise groups: water and land-based exercise (WL) or water and land-based exercise plus treadmill training (TWL). The water and land-based exercise group performed one water-based exercise and one land-based exercise session per week for 15 weeks. Participants in the water and land-based exercise plus treadmill training added two sessions of treadmill training to this schedule. The Senior Fitness Test (SFT) was used to assess the sample's fitness level. RESULTS: Participants in the water and land-based exercise Group experienced significant benefits in the disease impact (UPDRS t = 3.083; p = 0.029) and quality of life (PDQ-39 t = 2.942; p = 0.036). The addition of treadmill training did not have any significant effect on these variables. Both programs showed similar effects on the fitness components evaluated. CONCLUSION: Adding treadmill training to a combination of water and land-based exercise programs may have limited effects on quality of life and the impact on the disease. PMID- 27372365 TI - Real-life experience with fampridine (Fampyra(r)) for patients with multiple sclerosis and gait disorders. AB - BACKGROUND: Fampridine is a broad-spectrum voltage-dependent potassium channel blocker that enhances synaptic transmission. The drug has been shown to be able to ameliorate conduction in demyelinated axons, thereby leading to improved gait in patients with multiple sclerosis (MS). OBJECTIVE: To assess the "real-life" efficacy and safety of fampridine prescribed for gait disorders in MS. This was an observational and prospective study carried out at MS Units participating in the Brazilian Multiple Sclerosis Study Group. METHODS: Patients with MS and gait disorders were prescribed fampridine (10 mg twice a day), irrespectively of the degree of disability determined by MS. Neurological disability determined by MS was assessed with the expanded disability scale score (EDSS). Outcomes for efficacy and safety of the drug were evaluated by the 25 foot-walk test and by the adverse events of fampridine. RESULTS: The time taken to walk 25 feet decreased by 20% or more in 62 patients (70%). Twenty-five patients were considered to be non-responders to this treatment. Improvement in walking speed was independent of improvement of disability. Mild or moderate adverse events were reported in 8% of patients. CONCLUSION: Fampridine is an efficient and safe therapeutic option for patients with MS and gait disorders. PMID- 27372366 TI - Relationships between trunk performance, gait and postural control in persons with multiple sclerosis. AB - BACKGROUND: Multiple sclerosis (MS) is a chronic progressive disease of the central nervous system. Compared to healthy individuals, persons with multiple sclerosis (PwMS) have increased postural sway in quiet stance, decreased gait speed and increased fall incidence. Trunk performance has been implicated in postural control, gait dysfunction, and fall prevention in older adults. However, the relationship of trunk performance to postural control and gait has not been adequately studied in PwMS. OBJECTIVE: To compare trunk muscle structure and performance in PwMS to healthy age and gendered-matched controls (HC); to determine the effects of isometric trunk endurance testing on postural control in both populations; and to determine the relationship of trunk performance with postural control, gait and step activity in PwMS. METHODS: Fifteen PwMS and HC completed ultrasound imaging of trunk muscles, 10 m walk test, isometric trunk endurance tests, and postural sway test. Participants wore a step activity monitor for 7 days. RESULTS: PwMS had worse isometric trunk endurance compared to HC. PwMS trunk flexion endurance negatively correlated to several postural control measures and positively correlated to gait speed and step activity. CONCLUSIONS: Clinicians should consider evaluation and interventions directed at impaired trunk endurance in PwMS. PMID- 27372367 TI - Meta-analysis about cognitive intervention effect applied to dementia patients. AB - OBJECTIVE: The study tries to explore what effects multiple cognitive intervention, computer-based intervention, and memory training program had on dementia patients through meta-analysis. METHOD: Data was collected using an overseas search engine and 13 pieces of research published from January 2001 to April 2015 were selected. On papers that fit the selection criteria qualitative evaluation was conducted using Jadad evaluation and using pre-post average, standard deviation, and sample size of cognitive function, meta-analysis was conducted. RESULTS: The 13 studies selected included 6 multiple interventions, 4 computer-based interventions, and 3 memory training programs. In the Jadad evaluation all had 3 points or higher and there were 474 research participants and in the result of effect size analysis memory training intervention was found to be 'large effect size', computer-based intervention 'medium effect size', and multiple cognitive intervention 'small effect size'. All three intervention methods were all statistically significant (p < 0.05). CONCLUSION: It was found that the effect on dementia patients was in the order of memory training intervention, computer-based intervention, and multiple cognitive intervention. Clinically, this can be objective basis for treatment method for cognitive intervention of dementia patients. PMID- 27372368 TI - Exploring interest and goals for videoconferencing delivered cognitive rehabilitation with rural individuals with mild cognitive impairment or dementia. AB - BACKGROUND: Goal oriented cognitive rehabilitation is a promising intervention for individuals diagnosed with mild cognitive impairment (MCI) or dementia due to Alzheimer Disease (AD). Videoconferencing delivered cognitive rehabilitation is a potential avenue for increasing accessibility for rural patients and their families. OBJECTIVE: First, we were concerned with the accessibility of the treatment for individuals in rural and remote areas. Second, client-centered goal setting was explored by asking this sample about their goals for cognitive rehabilitation. METHOD: We mailed questions to all active patients with diagnoses of MCI or dementia due to AD of a rural memory clinic and compare features of the responders versus the non-responders. We asked about interest in videoconferencing delivered treatment and about goals for cognitive rehabilitation, which were thematically analyzed. RESULTS: The responders (N = 25) were similar to non-responders in severity, depression, and caregiver burden. Of the responders, 80% were interested in videoconferencing developed treatment. A thematic analysis coded 95% of responses as amenable to cognitive rehabilitation. Participants' goals were focused on memory, household activities, other cognitive domains, recreation, and higher order tasks. CONCLUSIONS: This work informs the development of both in-person and videoconferencing delivered cognitive rehabilitation for individuals diagnosed with MCI or dementia. PMID- 27372369 TI - Animal and human models to understand ageing. AB - Human ageing is the gradual decline in organ and tissue function with increasing chronological time, leading eventually to loss of function and death. To study the processes involved over research-relevant timescales requires the use of accessible model systems that share significant similarities with humans. In this review, we assess the usefulness of various models, including unicellular yeasts, invertebrate worms and flies, mice and primates including humans, and highlight the benefits and possible drawbacks of each model system in its ability to illuminate human ageing mechanisms. We describe the strong evolutionary conservation of molecular pathways that govern cell responses to extracellular and intracellular signals and which are strongly implicated in ageing. Such pathways centre around insulin-like growth factor signalling and integration of stress and nutritional signals through mTOR kinase. The process of cellular senescence is evaluated as a possible underlying cause for many of the frailties and diseases of human ageing. Also considered is ageing arising from systemic changes that cannot be modelled in lower organisms and instead require studies either in small mammals or in primates. We also touch briefly on novel therapeutic options arising from a better understanding of the biology of ageing. PMID- 27372370 TI - Discoidin Domains as Emerging Therapeutic Targets. AB - Discoidin (DS) domains are found in eukaryotic and prokaryotic extracellular and transmembrane multidomain proteins. These small domains play different functional roles and can interact with phospholipids, glycans, and proteins, including collagens. DS domain-containing proteins are often involved in cellular adhesion, migration, proliferation, and matrix-remodeling events, while some play a major role in blood coagulation. Mutations in DS domains have been associated with various disease conditions. This review provides an update on the structure, function, and modulation of the DS domains, with a special emphasis on two circulating blood coagulation cofactors, factor V and factor VIII, and the transmembrane neuropilin receptors that have been targeted for inhibition by biologics and small chemical compounds. PMID- 27372371 TI - Therapeutic progress in amyotrophic lateral sclerosis-beginning to learning. AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with motor neuron degeneration, muscle weakness, paralysis and finally death. The proposed mechanisms of ALS include glutamate excitotoxicity, oxidative stress, inflammation, mitochondrial dysfunction, apoptosis and proteasomal dysfunction. Although numerous pathological mechanisms have been explained, ALS remains incurable disease because of failure of clinical trials and lack of any effective therapy. The rapid advancement in genetic discoveries in ALS emphasizes the point that ALS is a multi-subtype syndrome rather than a single disease. This can be argued as one of the single reason why many previous therapeutic drug trials have failed. Efforts to develop novel ALS treatments which target specific pathomechanisms are currently being pursued. Herein, we review the recent discovery and preclinical characterization of neuroprotective compounds and compare their effects on disease onset, duration and survival. Furthermore, the structure-activity relationships of these agents are analyzed with the overall goal of developing a screening strategy for future clinical applications. PMID- 27372372 TI - Obesity Paradox in Off-Pump Coronary Artery Bypass Surgery: Does It Benefit the Elderly? AB - BACKGROUND: The obesity paradox is a well-known phenomenon in cardiovascular disease; how it interferes with coronary artery revascularization remains controversial. The purpose of this study was to investigate the impact of obesity body mass index (BMI > 30; in kg/m2) on short- and long-term survival and major adverse cardiovascular event (MACE)-free survival in obese patients after off pump coronary artery bypass operation. METHODS: We retrospectively reviewed our prospective cohort of 1,400 consecutive and systematic patients who underwent off pump coronary artery bypass operation between September 1996 and November 2007 and identified 448 (32%) with preoperative BMI greater than 30. RESULTS: Patients with BMI greater than 30 patients were younger and had a higher prevalence of diabetes, dyslipidemia, hypertension, and percutaneous coronary interventions than patients with BMI less than 30. Thirty-day mortality and perioperative myocardial infarction were similar in both groups. No significant difference was observed for wound infections, sternal dehiscence, and reoperation for bleeding. Overall, long-term survival was comparable in the two groups, although obese patients older than 65 years had a better survival than the nonobese patients even after correction for risk factors (p = 0.04). MACE-free survival at 10 years was 65.3% +/- 5.7% in obese and 76.3% +/- 2.3% in nonobese patients (p = 0.007). Statistical significance was maintained (p = 0.008) after correction for risk factors. Among MACE, only new episodes of congestive heart failure were more prevalent in obese patients (p = 0.002). CONCLUSIONS: In our series of off-pump coronary artery bypass operation, obesity was not an independent cause of short- and long-term mortality and was shown beneficial for older patients. However, obese patients had a lower MACE-free survival because of an increased incidence of rehospitalization for congestive heart failure. PMID- 27372373 TI - Long-Term Survival in Patients With Acute Kidney Injury After Acute Type A Aortic Dissection Repair. AB - BACKGROUND: Although acute kidney injury (AKI) is known as a serious complication after operation for acute type A aortic dissection (AAAD), the long-term impact of AKI remains unclear. The aim of the present study is to investigate the long term survival in patients with AKI after operation for AAAD. METHODS: This study included 403 patients who underwent operation for AAAD from 1990 to 2011 at Jichi Medical University, Saitama Medical Center. Postoperative AKI was identified according to the Kidney Disease Improving Global Outcomes criteria. Kaplan-Meier survival analysis and Cox proportional hazards regression were modeled to analyze the association between the AKI stage and postoperative long-term survival. RESULTS: Of 403 patients, 181 (44.9%) experienced postoperative AKI. Kaplan-Meier estimates for long-term survival were significantly different among patients without AKI and patients with stage 1, 2, and 3 AKI (p < 0.001). Hazard ratios of long-term survival for patients with stages 1, 2, and 3 AKI compared with patients without AKI were 1.38 (95% confidence interval [CI]: 0.84 to 2.26), 1.82 (95% CI: 0.95 to 3.51), and 3.79 (95% CI: 1.95 to 7.37), respectively. More patients with AKI died because of cardiovascular disease after discharge than patients without AKI (1.8% versus 6.0%, p = 0.03). CONCLUSIONS: Stage 3 AKI is significantly associated with lower long-term survival after operation for AAAD. Patient follow-up after discharge that focuses on cardiovascular issues may benefit patients who survive AKI after AAAD operation. PMID- 27372374 TI - Reply. PMID- 27372375 TI - Presentation and Medical Management of Fibrocartilaginous Embolism in the Emergency Department. AB - BACKGROUND: Fibrocartilaginous embolism is an exceedingly rare condition that was formerly a clinical diagnosis based on mechanism of injury, physical examination findings, and older magnetic resonance imaging (MRI) technologies without a specific histologic diagnosis. Spinal cord MRI diffusion-weighted imaging allows for a more specific diagnosis. CASE REPORT: A 14-year-old male felt a sudden pop in his back while running sprints in his gym class. He slowly developed bilateral lower extremity weakness and urinary incontinence, prompting an emergency department evaluation. A MRI scan of his lumbar spine revealed degeneration, desiccation, and bulging of the T12-L1 disc with an accompanying subacute Schmorl's nodule. There was adjacent cord swelling and central cord T2 hyperintensity, with accompanying restricted diffusion consistent with spinal cord infarction. These findings, in conjunction with paraplegia and mechanism of injury, were highly suggestive of fibrocartilaginous embolism. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: An emergent MRI scan with the proper sequencing and immediate consultation with a spine surgery specialist are important to exclude a compressive myelopathy that would necessitate acute surgical decompression. There is significant uncertainty in the initial management and stabilization of this rare condition that has not been addressed in the emergency medicine literature. PMID- 27372376 TI - Care of the Critically Ill Pregnant Patient and Perimortem Cesarean Delivery in the Emergency Department. AB - BACKGROUND: Maternal resuscitation in the emergency department requires planning and special consideration of the physiologic changes of pregnancy. Perimortem cesarean delivery (PMCD) is a rare but potentially life-saving procedure for both mother and fetus. Emergency physicians should be aware of the procedure's indications and steps because it needs to be performed rapidly for the best possible outcomes. OBJECTIVE: We sought to review the approach to the critically ill pregnant patient in light of new expert guidelines, including indications for PMCD and procedural techniques. DISCUSSION: The prevalence of maternal cardiac arrest and survival outcomes of PMCD in the emergency department setting are difficult to estimate. Advanced cardiovascular life support protocols should be followed in maternal arrest with special considerations made based on the physiologic changes of pregnancy. The latest recommendations for maternal resuscitation are reviewed, including advance planning, rapid determination of gestational age, emergent delivery, and postprocedure considerations for PMCD. CONCLUSIONS: Maternal resuscitation requires knowledge of physiologic changes and evidence-based recommendations. PMCD outcomes are best for both mother and fetus when the procedure is performed rapidly and efficiently in the appropriate setting. Emergency physicians should be familiar with this unique clinical scenario so they are adequately prepared to intervene in order to improve maternal and fetal morbidity and mortality. PMID- 27372377 TI - The Integration of Electronic Medical Student Evaluations Into an Emergency Department Tracking System is Associated With Increased Quality and Quantity of Evaluations. AB - BACKGROUND: Medical student evaluations are essential for determining clerkship grades. Electronic evaluations have various advantages compared to paper evaluations, such as increased ease of collection, asynchronous reporting, and decreased likelihood of becoming lost. OBJECTIVES: To determine whether electronic medical student evaluations (EMSEs) provide more evaluations and content when compared to paper shift card evaluations. METHODS: This before and after cohort study was conducted over a 2.5-year period at an academic hospital affiliated with a medical school and emergency medicine residency program. EMSEs replaced the paper shift evaluations that had previously been used halfway through the study period. A random sample of the free text comments on both paper and EMSEs were blindly judged by medical student clerkship directors for their helpfulness and usefulness. Logistic regression was used to test for any relationship between quality and quantity of words. RESULTS: A total of 135 paper evaluations for 30 students and then 570 EMSEs for 62 students were collected. An average of 4.8 (standard deviation [SD] 3.2) evaluations were completed per student using the paper version compared to 9.0 (SD 3.8) evaluations completed per student electronically (p < 0.001). There was an average of 8.8 (SD 8.5) words of free text evaluation on paper evaluations when compared to 22.5 (SD 28.4) words for EMSEs (p < 0.001). A statistically significant (p < 0.02) association between quality of an evaluation and the word count existed. CONCLUSIONS: EMSEs that were integrated into the emergency department tracking system significantly increased the number of evaluations completed compared to paper evaluations. In addition, the EMSEs captured more "helpful/useful" information about the individual students as evidenced by the longer free text entries per evaluation. PMID- 27372378 TI - Bleomycin-Induced Flagellate Hyperpigmentation. PMID- 27372379 TI - Assessment of TruviewPCD videolaryngoscope for intubation in children. AB - OBJECTIVE: The aim of this observational prospective study was to evaluate the usefulness of TruviewPCD for tracheal intubation in clinical practice, and to provide data for future studies. MATERIAL AND METHOD: A study was conducted on 86 consecutive children undergoing ear, nose and throat (ENT) or paediatric procedures under general anaesthesia with tracheal intubation. Children with two or more difficult airway criteria were excluded. A descriptive statistical analysis was performed. RESULTS: Eighty-three patients were successfully intubated with TruviewPCD. Demographic data: Age 4.9 (2.8) years, weight 19.5 (7.7)kg. Seventy-nine children needed one attempt and four required two attempts at intubation. Time for glottis view and tracheal intubation was 10.8 (5.6) and 30 [27.9-37] seconds, respectively. Eighty-one patients were classified as easy or very easy to intubate, and only two cases were considered difficult. No significant complications were registered. CONCLUSIONS: TruviewPCD is a good device for paediatric airway management. It would be interesting to have an intermediate blade between size 1 and 2, as the difference between both is too wide. PMID- 27372380 TI - Analgesic effect of a single-dose of perineural dexamethasone on ultrasound guided femoral nerve block after total knee replacement. AB - INTRODUCTION: Total knee replacement is usually a very painful procedure. A single-dose of femoral nerve block has been shown to provide similar analgesia to an epidural, with fewer side effects, but limited in time. OBJECTIVE: To compare the analgesia provided by dexamethasone used at perineural level in the femoral nerve block after total knee replacement with the one used at intravenous level, and with that of a control group. MATERIAL AND METHODS: A prospective, randomised, double-blind controlled trial was conducted on 81 patients randomly assigned to one of three groups: 1)IV dexamethasone (8mg); 2)perineural dexamethasone (8mg), and 3)placebo. All patients received 20ml of ropivacaine 0.5% for femoral nerve block. The primary outcome was the duration of the sensory analgesic block of the femoral nerve block. The secondary outcomes included pain intensity measurements, patient satisfaction, and incidence of complications. RESULTS: Randomisation was effective. Analgesia duration was significantly higher (P<.0001) in the perineural dexamethasone group (mean 1152.2min, 95% confidence interval [95% CI]: 756.9-1547.6) in comparison with the control group (mean 186min, 95%CI: 81.2-292) and dexamethasone IV group (mean 159.4min, 95%CI: 109.8 209). Postoperative pain, complications and side effects were also lower in this group. CONCLUSIONS: Dexamethasone prolongs sensory block of single dose of femoral nerve block using ropivacaine. It also provides better analgesia and patient satisfaction, with fewer side effects. PMID- 27372381 TI - Hypoxia inducible factor 1alpha: A critical factor for the immune response to pathogens and Leishmania. AB - Organisms typically react to foreign pathogens by initiating an inflammatory response. However, in order to limit inflammatory tissue injury, it is essential for the organism to maintain the balance between inflammatory and anti inflammatory responses. Dysregulation of this process can result in the strong inhibition of protective pro-inflammatory responses, and ultimately in pathogen persistence. Chronic infections are often associated with inflammation and tissue disruption. Inflamed tissues are characterized by low levels of oxygen and glucose, a microenvironment that triggers the stabilization of the hypoxia inducible transcription factor HIF-1alpha. HIF-1alpha is the master regulator of the response to hypoxia. Here, we review the role of HIF-1alpha in the immune response to various pathogens and we highlight how certain microorganisms, including Leishmania parasites, have evolved to hijack the HIF-1 pathway to their advantage. PMID- 27372382 TI - Cylindromatosis (Cyld) gene mutation in T cells promotes the development of an IL 9-dependent allergic phenotype in experimental asthma. AB - Cylindromatosis (CYLD) is a ubiquitously expressed deubiquitinating enzyme which removes activating ubiquitin residues from important signaling molecules of the NF-kappaB pathway. In CYLDex7/8 transgenic mice, a naturally occurring short isoform (sCYLD) is overexpressed in the absence of full length CYLD, leading to excessive NF-kappaB activity. Herein, we investigated the impact of the CYLDex7/8 mutation selectively in T cells on the development of experimental allergic airway disease induced by sensitization and challenge with ovalbumin. Compared with their wildtype littermates, mice bearing the T cell-specific mutation (CD4+CYLDex7/8) display stronger eosinophilia and mucus production in the lungs and higher IgE serum levels. The reason for these observations is excessive production of T cell-derived IL-9, a cytokine to whom allergy-promoting properties were ascribed. Consequently, blockade of IL-9 in CD4+CYLDex7/8 mice alleviates the development of disease symptoms. Thus, by polarization of the T cell cytokine response, sCYLD can favor the development of allergic airway disease. PMID- 27372383 TI - A Quantitative Analysis of Cold Water for Human Consumption in Hospitals in Spain. AB - An estimation of the water used for human consumption in hospitals is essential to determine possible savings and to fix criteria to improve the design of new water consumption models. The present work reports on cold water for human consumption (CWHC) in hospitals in Spain and determines the possible savings. In the period of 2005-2012, 80 Eco-Management and Audit Schemes (EMAS) from 20 hospitals were analysed. The results conclude that the average annual consumption of CWHC is 1.59 m(3)/m(2) (with a standard deviation of 0.48 m(3)/m(2)), 195.85 m(3)/bed (standard deviation 70.07 m(3)/bed), or 53.69 m(3)/worker (standard deviation 16.64 m(3)/worker). The results demonstrate the possibility of saving 5,600,000 m(3) of water per year. Assuming the cost of water as approximately 1.22 ?/m(3), annual savings are estimated as 6,832,000 ?. Furthermore, 2,912 MWh of energy could be saved, and the emission of 22,400 annual tonnes of CO2 into the atmosphere could be avoided. PMID- 27372384 TI - Dosimetric evaluation of total marrow irradiation using 2 different planning systems. AB - This study compared 2 different treatment planning systems (TPSs) for quality and efficiency of total marrow irradiation (TMI) plans. The TPSs used in this study were VOxel-Less Optimization (VoLO) (Accuray Inc, Sunnyvale, CA) using helical dose delivery on a Tomotherapy Hi-Art treatment unit and Eclipse (Varian Medical Systems Inc, Palo Alto, CA) using volumetric modulated arc therapy (VMAT) dose delivery on a Varian iX treatment unit. A total dose of 1200cGy was prescribed to cover 95% of the planning target volume (PTV). The plans were optimized and calculated based on a single CT data and structure set using the Alderson Rando phantom (The Phantom Laboratory, Salem, NY) and physician contoured target and organ at risk (OAR) volumes. The OARs were lungs, heart, liver, kidneys, brain, and small bowel. The plans were evaluated based on plan quality, time to optimize the plan and calculate the dose, and beam on time. The resulting mean and maximum doses to the PTV were 1268 and 1465cGy for VoLO and 1284 and 1541cGy for Eclipse, respectively. For 5 of 6 OAR structures the VoLO system achieved lower mean and D10 doses ranging from 22% to 52% and 3% to 44%, respectively. Total computational time including only optimization and dose calculation were 0.9 hours for VoLO and 3.8 hours for Eclipse. These times do not include user dependent target delineation and field setup. Both planning systems are capable of creating high-quality plans for total marrow irradiation. The VoLO planning system was able to achieve more uniform dose distribution throughout the target volume and steeper dose fall off, resulting in superior OAR sparing. VoLO's graphics processing unit (GPU)-based optimization and dose calculation algorithm also allowed much faster creation of TMI plans. PMID- 27372385 TI - Exposure of marine mussels Mytilus spp. to polystyrene microplastics: Toxicity and influence on fluoranthene bioaccumulation. AB - The effects of polystyrene microbeads (micro-PS; mix of 2 and 6 MUm; final concentration: 32 MUg L(-1)) alone or in combination with fluoranthene (30 MUg L( 1)) on marine mussels Mytilus spp. were investigated after 7 days of exposure and 7 days of depuration under controlled laboratory conditions. Overall, fluoranthene was mostly associated to algae Chaetoceros muelleri (partition coefficient Log Kp = 4.8) used as a food source for mussels during the experiment. When micro-PS were added in the system, a fraction of FLU transferred from the algae to the microbeads as suggested by the higher partition coefficient of micro-PS (Log Kp = 6.6), which confirmed a high affinity of fluoranthene for polystyrene microparticles. However, this did not lead to a modification of fluoranthene bioaccumulation in exposed individuals, suggesting that micro-PS had a minor role in transferring fluoranthene to mussels tissues in comparison with waterborne and foodborne exposures. After depuration, a higher fluoranthene concentration was detected in mussels exposed to micro-PS and fluoranthene, as compared to mussels exposed to fluoranthene alone. This may be related to direct effect of micro-PS on detoxification mechanisms, as suggested by a down regulation of a P-glycoprotein involved in pollutant excretion, but other factors such as an impairment of the filtration activity or presence of remaining beads in the gut cannot be excluded. Micro-PS alone led to an increase in hemocyte mortality and triggered substantial modulation of cellular oxidative balance: increase in reactive oxygen species production in hemocytes and enhancement of anti-oxidant and glutathione-related enzymes in mussel tissues. Highest histopathological damages and levels of anti-oxidant markers were observed in mussels exposed to micro-PS together with fluoranthene. Overall these results suggest that under the experimental conditions of our study micro-PS led to direct toxic effects at tissue, cellular and molecular levels, and modulated fluoranthene kinetics and toxicity in marine mussels. PMID- 27372386 TI - Adjuvant Proton Beam Therapy in the Management of Thymoma: A Dosimetric Comparison and Acute Toxicities. AB - BACKGROUND: We evaluated the dosimetric differences between proton beam therapy (PBT) and intensity modulated radiation therapy (IMRT) for resected thymoma. We simultaneously report our early clinical experience with PBT in this cohort. PATIENTS AND METHODS: We identified 4 patients with thymoma or thymic carcinoma treated at our center from 2012 to 2014 who completed adjuvant PBT to a median dose of 57.0 cobalt Gy equivalents (CGE; range, 50.4-66.6 CGE) after definitive resection. Adjuvant radiation was indicated for positive (n = 3) or close margin (n = 1). Median age was 45 (range, 32-70) years. Stages included II (n = 2), III (n = 1), and IVA (n = 1). Analogous IMRT plans were generated for each patient for comparison, and preset dosimetric endpoints were evaluated. Early toxicities were assessed according to retrospective chart review. RESULTS: Compared with IMRT, PBT was associated with lower mean doses to the lung (4.6 vs. 8.1 Gy; P = .02), esophagus (5.4 vs. 20.6 Gy; P = .003), and heart (6.0 vs. 10.4 Gy; P = .007). Percentages of lung, esophagus, and heart receiving radiation were consistently lower in the PBT plans over a wide range of radiation doses. There was no difference in mean breast dose (2.68 vs. 3.01 Gy; P = .37). Of the 4 patients treated with PBT, 3 patients experienced Grade 1 radiation dermatitis, and 1 patient experienced Grade 2 dermatitis, which resolved after treatment. With a median follow-up of 5.5 months, there were no additional Grade >= 2 acute or subacute toxicities, including radiation pneumonitis. CONCLUSION: PBT is clinically well tolerated after surgical resection of thymoma, and is associated with a significant reduction in dose to critical structures without compromising coverage of the target volume. Prospective evaluation and longer follow-up is needed to assess clinical outcomes and late toxicities. PMID- 27372387 TI - APIC salutes the 2016 Heroes of Infection Prevention. PMID- 27372388 TI - Tetanus, diphtheria, and acellular pertussis vaccination among women of childbearing age-United States, 2013. AB - The incidence of pertussis in the United States has increased since the 1990s. Tetanus, diphtheria, and acellular pertussis (Tdap) vaccination of pregnant women provides passive protection to infants. Tdap vaccination is currently recommended for pregnant women during each pregnancy, but coverage among pregnant women and women of childbearing age has been suboptimal. Data from the 2013 Behavioral Risk Factor Surveillance System (BRFSS) and 2013 National Health Interview Survey (NHIS) were used to determine national and state-specific Tdap vaccination coverage among women of childbearing age by self-reported pregnancy status at the time of the survey. Although this study could not assess coverage of Tdap vaccination received during pregnancy because questions on whether Tdap vaccination was received during pregnancy were not asked in BRFSS and NHIS, demographic and access-to-care factors associated with Tdap vaccination coverage in this population were assessed. Tdap vaccination coverage among all women 18-44 years old was 38.4% based on the BRFSS and 23.3% based on the NHIS. Overall, coverage did not differ by pregnancy status at the time of the survey. Coverage among all women 18-44 years old varied widely by state. Age, race and ethnicity, education, number of children in the household, and access-to-care characteristics were independently associated with Tdap vaccination in both surveys. We identified associations of demographic and access-to-care characteristics with Tdap vaccination that can guide strategies to improve vaccination rates in women during pregnancy. PMID- 27372389 TI - Prevention of transmitted infections in a pet therapy program: An exemplar. AB - The focus of the patient experience in health care delivery has afforded the opportunity to integrate pet therapy as a part of patient care. The purpose of this article is to present the implementation of a pet therapy program that includes guidelines for the prevention of transmitted infections. Consideration of infection prevention strategies has resulted in a 16-year program with no documented incidences of transmitted infections, averaging 20,000 pet therapy interactions per year. PMID- 27372390 TI - The first point prevalence survey of health care-associated infection and antimicrobial use in a Japanese university hospital: A pilot study. AB - BACKGROUND: Point prevalence surveys (PPSs) in Japanese hospitals have not yet been reported. The purpose of this pilot PPS study was to evaluate the epidemiology of health care-associated infections (HAIs) and antimicrobial use in a Japanese tertiary university hospital. METHODS: A 1-day, cross-sectional PPS was performed at a Japanese university hospital. Data on demographics, active HAIs, and antimicrobial use of all inpatients were collected using a data collection form. RESULTS: Of 841 patients, 85 (10.1%) had 90 active HAIs, and 308 patients (36.6%) were administered 494 antimicrobials. Among the 90 HAIs and 58 pathogens, the most frequent infection and isolated pathogen were pneumonia (20.0%) and Enterobacteriaceae (27.6%), respectively. Of the 118 antimicrobials used for treatment of HAIs, carbapenems were the most frequently administered category of antimicrobials (22.9%). In regard to antimicrobials for surgical prophylaxis, 37 of 119 (31.1%) were administered to patients on postoperative day 3 or later, and 48 of 119 (40.3%) were administered orally. CONCLUSIONS: The incidence of HAIs is higher than in other developed countries. The social and medical situation in Japan may affect patient demographics, active HAIs, and antimicrobial use. Multicenter PPSs are necessary to uncover the real epidemiology of HAIs and antimicrobial use in Japan. PMID- 27372391 TI - Cancer Risk in Beckwith-Wiedemann Syndrome: A Systematic Review and Meta-Analysis Outlining a Novel (Epi)Genotype Specific Histotype Targeted Screening Protocol. AB - OBJECTIVE: To compare tumor risk in the 4 Beckwith-Wiedemann syndrome (BWS) molecular subgroups: Imprinting Control Region 1 Gain of Methylation (ICR1-GoM), Imprinting Control Region 2 Loss of Methylation (ICR2-LoM), Chromosome 11p15 Paternal Uniparental Disomy (UPD), and Cyclin-Dependent Kinase Inhibitor 1C gene (CDKN1C) mutation. STUDY DESIGN: Studies on BWS and tumor development published between 2000 and 2015 providing (epi)genotype-cancer correlations with histotype data were reviewed and meta-analysed with cancer histotypes as measured outcome and (epi)genotype as exposure. RESULTS: A total of 1370 patients with BWS were included: 102 developed neoplasms (7.4%). Tumor prevalence was 2.5% in ICR2-LoM, 13.8% in UPD, 22.8% in ICR1-GoM, and 8.6% in patients with CDKN1C mutations. Cancer ORs were 12.8 in ICR1-GoM, 6.5 in UPD, and 2.9 in patients with CDKN1C mutations compared with patients with ICR2-LoM. Wilms tumor was associated with ICR1-GoM (OR 68.3) and UPD (OR 13.2). UPD also was associated with hepatoblastoma (OR 5.2) and adrenal carcinoma (OR 7.0), and CDKN1C mutations with neuroblastic tumors (OR 7.2). CONCLUSION: Cancer screening in BWS could be differentiated on the basis of (epi)genotype and target specific histotypes. Patients with ICR1-GoM and UPD should undergo renal ultrasonography scanning, given their risk of Wilms tumor. Alpha feto protein monitoring for heptaoblastoma is suggested in patients with UPD. Adrenal carcinoma may deserve screening in patients with UPD. Patients with CDKN1C mutations may deserve neuroblastoma screening based on urinary markers and ultrasonography scanning. Finally, screening appears questionable in cases of ICR2-LoM, given low tumor risk. PMID- 27372392 TI - The Electronic Medical Record and Computerized Physician Order Entry: Challenges and Opportunities for Pediatrics. PMID- 27372393 TI - Mobility Status as a Predictor of Obesity, Physical Activity, and Screen Time Use among Children Aged 5-11 Years in the United States. AB - OBJECTIVE: To examine physical activity participation, screen time habits, and the prevalence of overweight/obesity among children in the general population with mobility limitations and those enrolled in special education services. STUDY DESIGN: An observational, cross-sectional analysis of the 2011-2014 National Health and Nutrition Examination Survey, a representative sample of the US population. Mobility limitations, special education services utilization, proxy reported physical activity and screen time, and overweight/obesity status were assessed in children aged 5-11 years. RESULTS: Boys with mobility limitations were less likely to meet physical activity guidelines (>=60 minutes daily) compared with those with no limitations (58.1% vs 74.4%, adjusted F = 4.61, P = .04). In a logistic regression model, boys with mobility limitations had significantly lower odds (0.42, 95% CI 0.20-0.86) of meeting physical activity guidelines. The prevalence of children meeting screen time recommendations (<=2 hours daily) among those receiving special education services (42.4%) was lower than children not receiving services (53.2%; adjusted F = 8.87, P < .01). In a logistic regression model, children receiving special education services showed a trend toward significantly lower odds (0.74, 95% CI 0.54-1.03, P = .07) of meeting screen time recommendations. No statistically significant differences for overweight/obesity were found. CONCLUSIONS: Clear differences were present in physical activity between boys with and without mobility limitations. Furthermore, children receiving special education services demonstrated a lower likelihood of meeting screen time recommendations. Children with disabilities may benefit from targeted interventions aimed at increasing physical activity while decreasing screen time. PMID- 27372394 TI - Readmissions for Heart Failure in Children. AB - OBJECTIVE: To assess the frequency of inpatient 30-day readmission for heart failure in children with cardiomyopathy discharged after an admission for heart failure and the impact of discharge pharmacotherapy on readmissions. STUDY DESIGN: The Pediatric Health Information System Database was queried for patients <=18 years of age with an International Classification of Diseases, Ninth Revision code for heart failure (428.xx) or cardiomyopathy (425.xx) discharged from 2004 to 2013. Patients were excluded if they had congenital heart disease, expired on the initial admission, or underwent cardiac surgery. Patient admission characteristics were documented and discharge medications were captured. Frequency of 30-day readmission for heart failure was identified, and mixed effects multivariable logistic regression analysis was performed to determine factors significant for readmission. RESULTS: A total of 2386 patients met study criteria (52.1% male, median age 8.1 years [IQR 1.2-14.6 years]). Vasoactive medications were used in 70.3% of patients on initial admission, the most common of which was milrinone (62.8%). Angiotensin converting enzyme inhibitors and beta blockers were given at discharge to 67.4% and 35.9%, respectively. Frequency of 30-day readmission for heart failure was 12.9%. Duration of milrinone or beta blocker use at discharge and institutional heart failure patient volume were associated with a greater odds of 30-day readmission, whereas mechanical ventilation on initial admission was associated with decreased odds of readmission. CONCLUSIONS: Pediatric patients with cardiomyopathy and heart failure have a high frequency of heart failure-related 30-day readmission. Outpatient pharmacotherapy at discharge does not appear to influence readmission. PMID- 27372395 TI - Pathology of congenital Zika syndrome in Brazil: a case series. AB - BACKGROUND: Zika virus is an arthropod-borne virus that is a member of the family Flaviviridae transmitted mainly by mosquitoes of the genus Aedes. Although usually asymptomatic, infection can result in a mild and self-limiting illness characterised by fever, rash, arthralgia, and conjunctivitis. An increase in the number of children born with microcephaly was noted in 2015 in regions of Brazil with high transmission of Zika virus. More recently, evidence has been accumulating supporting a link between Zika virus and microcephaly. Here, we describe findings from three fatal cases and two spontaneous abortions associated with Zika virus infection. METHODS: In this case series, formalin-fixed paraffin embedded tissue samples from five cases, including two newborn babies with microcephaly and severe arthrogryposis who died shortly after birth, one 2-month old baby, and two placentas from spontaneous abortions, from Brazil were submitted to the Infectious Diseases Pathology Branch at the US Centers for Disease Control and Prevention (Atlanta, GA, USA) between December, 2015, and March, 2016. Specimens were assessed by histopathological examination, immunohistochemical assays using a mouse anti-Zika virus antibody, and RT-PCR assays targeting the NS5 and envelope genes. Amplicons of RT-PCR positive cases were sequenced for characterisation of strains. FINDINGS: Viral antigens were localised to glial cells and neurons and associated with microcalcifications in all three fatal cases with microcephaly. Antigens were also seen in chorionic villi of one of the first trimester placentas. Tissues from all five cases were positive for Zika virus RNA by RT-PCR, and sequence analyses showed highest identities with Zika virus strains isolated from Brazil during 2015. INTERPRETATION: These findings provide strong evidence of a link between Zika virus infection and different congenital central nervous system malformations, including microcephaly as well as arthrogryposis and spontaneous abortions. FUNDING: None. PMID- 27372396 TI - Surveillance of Zika virus infection and microcephaly in Brazil. PMID- 27372397 TI - Strengthening maternal immunisation to improve the health of mothers and infants. PMID- 27372398 TI - Congenital Zika virus syndrome in Brazil: a case series of the first 1501 livebirths with complete investigation. AB - BACKGROUND: In November, 2015, an epidemic of microcephaly was reported in Brazil, which was later attributed to congenital Zika virus infection. 7830 suspected cases had been reported to the Brazilian Ministry of Health by June 4, 2016, but little is known about their characteristics. We aimed to describe these newborn babies in terms of clinical findings, anthropometry, and survival. METHODS: We reviewed all 1501 liveborn infants for whom investigation by medical teams at State level had been completed as of Feb 27, 2016, and classified suspected cases into five categories based on neuroimaging and laboratory results for Zika virus and other relevant infections. Definite cases had laboratory evidence of Zika virus infection; highly probable cases presented specific neuroimaging findings, and negative laboratory results for other congenital infections; moderately probable cases had specific imaging findings but other infections could not be ruled out; somewhat probable cases had imaging findings, but these were not reported in detail by the local teams; all other newborn babies were classified as discarded cases. Head circumference by gestational age was assessed with InterGrowth standards. First week mortality and history of rash were provided by the State medical teams. FINDINGS: Between Nov 19, 2015, and Feb 27, 2015, investigations were completed for 1501 suspected cases reported to the Brazilian Ministry of Health, of whom 899 were discarded. Of the remainder 602 cases, 76 were definite, 54 highly probable, 181 moderately probable, and 291 somewhat probable of congenital Zika virus syndrome. Clinical, anthropometric, and survival differences were small among the four groups. Compared with these four groups, the 899 discarded cases had larger head circumferences (mean Z scores -1.54 vs -3.13, difference 1.58 [95% CI 1.45-1.72]); lower first-week mortality (14 per 1000 vs 51 per 1000; rate ratio 0.28 [95% CI 0.14-0.56]); and were less likely to have a history of rash during pregnancy (20.7% vs 61.4%, ratio 0.34 [95% CI 0.27-0.42]). Rashes in the third trimester of pregnancy were associated with brain abnormalities despite normal sized heads. One in five definite or probable cases presented head circumferences in the normal range (above -2 SD below the median of the InterGrowth standard) and for one third of definite and probable cases there was no history of a rash during pregnancy. The peak of the epidemic occurred in late November, 2015. INTERPRETATION: Zika virus congenital syndrome is a new teratogenic disease. Because many definite or probable cases present normal head circumference values and their mothers do not report having a rash, screening criteria must be revised in order to detect all affected newborn babies. FUNDING: Brazilian Ministry of Health, Pan American Health Organization, and Wellcome Trust. PMID- 27372399 TI - Zika and histopathology in first trimester infections. PMID- 27372400 TI - Inexperienced examiners and the Foot Posture Index: A reliability study. AB - The Foot Posture Index (FPI-6) is a reliable (experienced examiners) assessment tool used in clinical practice to classify foot posture. No work has been completed to determine the reliability of the FPI-6 between novice examiners. Therefore, the aim was to determine the inter-examiner reliability of the FPI-6 using two novice examiners (graduate level osteopathy students). The FPI-6 was used to classify the feet of 83 students recruited as part of a larger study. Data were collected simultaneously by both examiners, but there was no communication between them. The scoring system provided by the FPI-6 manual was used to assess all feet. Collated data were assessed between examiners for reliability based on raw, transformed and foot type scores. The inter-examiner reliability was high for both left (intra-class correlation coefficient ICC2,1 = 0.86) and right (ICC2,1 = 0.85) feet for the novice examiners. When data were assessed based on foot type classification the examiners agreed on 76% of the left feet and 82% of the right feet with Kappa values of 0.73 and 0.72 respectively. The FPI-6 is a robust clinical tool that can be reliably utilised by inexperienced clinicians. PMID- 27372401 TI - New Structural Insights into Translational Miscoding. AB - The fidelity of translation depends strongly on the selection of the correct aminoacyl-tRNA that is complementary to the mRNA codon present in the ribosomal decoding center. The ribosome occasionally makes mistakes by selecting the wrong substrate from the pool of aminoacyl-tRNAs. Here, we summarize recent structural advances that may help to clarify the origin of missense errors that occur during decoding. These developments suggest that discrimination between tRNAs is based primarily on steric complementarity and shape acceptance rather than on the number of hydrogen bonds between the molding of the decoding center and the codon anticodon duplex. They strengthen the hypothesis that spatial mimicry, due either to base tautomerism or ionization, drives infidelity in ribosomal translation. PMID- 27372402 TI - Dopaminergic Effects on Brown Adipose Tissue (DEBAT): A prospective physiological study. PMID- 27372403 TI - Patient perceptions and willingness to participate in clinical trials. AB - OBJECTIVE: To evaluate gynecologic oncology patients' perceptions and willingness to participate in randomized clinical trials (RCT) among an inner city population. METHODS: Informed consent was obtained. Demographics were collected and willingness to participate in a RCT was measured by the Attitudes on Randomized Trials Questionnaire (ARTQ). The Hospital Anxiety and Depression Scale estimated levels of anxiety and depression. A Perception Survey was created and tested as a screening tool for patients considering RCTs. Standard statistical tests were used. RESULTS: One hundred and one women participated, 54 (53.5%) were black, 31 (30.7%) were white, non-Hispanic and 15 (14.9%) were Hispanic. Screening for anxiety and depression revealed an 18.8% rate of moderate to severe anxiety and an 11.9% rate of moderate to severe depression. Willingness to participate in a RCT as measured by ARTQ scores was not significantly associated with race, levels of anxiety or depression. Twenty-eight percent of women would agree to participate in a clinical trial at baseline. An additional, 33 (32.7%), for a total of 61.4%, indicated agreement after targeted education with no statistical differences by race or psychological stressor. However, sixty-one percent of these women were black. The Perception Survey approximated the results of the ARTQ with reasonable accuracy (AUC 0.758, p<0.001) CONCLUSIONS: Neither race nor psychological stressor were significant indicators of willingness to participate in a RCT. Targeted education resulted in a majority of patients indicating willingness to participate in trials, especially among black women. Additionally, a novel screening tool was tested and performed well in this setting. PMID- 27372404 TI - Protective effect of Caralluma fimbriata against high-fat diet induced testicular oxidative stress in rats. AB - High-fat diet (HFD) promotes the oxidative stress formation, which in turn has hazardous effects on reproductive system and fertility. The objective of this study was to evaluate the protective effect of Caralluma fimbriata on high-fat diet-induced oxidative stress in the testis of rat. Male Wistar rats were randomly divided into five groups: Control (C), Control treated with CFE (C+ CFE), High fat diet fed (HFD), High fat diet fed treated with CFE (HFD+CFE) and High fat diet fed treated with Metformin (HFD+Met). CFE was orally administered (200mg/kg body weight) for 90days to groups-C+CFE and HFD+CFE rats. The effects of HF-diet on the reproductive organs were determined by measuring relative and absolute testes and epididymal fat pads weights. Regarding testes antioxidant status, high-fat fed rats showed higher levels of lipid peroxidation, protein oxidation, polyol pathway enzymes and lower GSH levels and lower activities of antioxidants, while CFE treatment prevented all these observed abnormalities. The present study clearly indicates that CFE offers a significant protection against HF-diet induced testicular oxidative stress in rats. PMID- 27372405 TI - Synergistic inhibition of sunitinib and ethaselen against human colorectal cancer cells proliferation. AB - Sunitinib, a multi-targeted tyrosine kinase inhibitor, has been widely used in the therapy of advanced renal cell cancer and imatinib-resistant gastrointestinal stromal tumors. However, little benefits could be obtained from sunitinib for patients with other types of solid tumors including colorectal cancer (CRC). Ethaselen (BBSKE), a specific thioredoxin reductase 1 inhibitor, has shown convincing anticancer effects both in vivo and in vitro. In this study, we explored the combinatory effect of sunitinib and BBSKE in human CRC cell lines LoVo, HT-29 and RKO. Cotreatment of BBSKE and sunitinib with the ratio of 2:1 for 24h displayed synergistic effect against CRC cells proliferation. Apoptosis analysis also revealed that combination treatment of BBSKE and sunitinib (2:1) for 24h induced higher apoptosis rate than either single treatment. The synergistic effect against LoVo cells proliferation may be explained by sharp reduction of Bcl-2/Bax protein expression ratio, decrease of pro-Caspase-3 protein expression along with significantly augmented Caspase-3 enzymatic activity, and release of cytochrome C from mitochondria to cytoplasm in the combination treatment group. The significant inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) phosphorylation might also account for the synergism in cotreatment group. In short, sunitinib plus BBSKE is perhaps a promising strategy for colorectal cancer therapy. PMID- 27372406 TI - Protective effect of Tephrosia purpurea in diabetic cataract through aldose reductase inhibitory activity. AB - PURPOSE: Tephrosia purpurea (T. purpurea) has been reported to prevent cataract formation in senile cataract model as well as proven effective in STZ induced type 1 diabetes. Aldose reductase (AR) is a key enzyme in the intracellular polyol pathway responsible for the development of diabetic cataract. OBJECTIVE: To investigate the effects of T. purpurea in the light of inhibition of aldose reductase enzyme in polyol pathway. METHODS: We studied the effects of alcoholic extract and flavonoid fraction of T. purpurea in streptozotocin (STZ, 45mg/kg, i.v.)-induced type I diabetic cataract in rats. The animals were divided into five groups as control, control treated with alcoholic and flavonoid fraction, diabetic control and diabetic treated with alcoholic and flavonoid fraction. In vitro aldose reductase inhibitory activity was also evaluated. Further, molecular docking study was performed with crystal structure of aldose reductase and its known chemical constituents of the plant. RESULTS: The IC50 value of alcoholic extract for aldose reductase inhibition was found to be 209.13MUg/ml, and that of flavonoid fraction was found to be 46.73MUg/ml. Administration of STZ produced significantly abnormal levels of serum glucose, serum insulin, soluble protein and antioxidants in the lens homogenate. Treatment with alcoholic extract and flavonoid fraction of T. purpurea were able to normalize these levels. Some of the active constituents of T. purpurea showed significant interactions with aldose reductase enzyme in molecular docking studies. CONCLUSIONS: Our data suggested that both the extracts might be helpful in delaying the development of diabetic cataract due to the presence of rutin and quercetin. This beneficial effect may be due to its significant inhibition of aldose reductase enzyme and anti-oxidant activity. PMID- 27372407 TI - Co-delivery of IL17RB siRNA and doxorubicin by chitosan-based nanoparticles for enhanced anticancer efficacy in breast cancer cells. AB - Overexpression of IL17RB is associated with poor prognosis and short survival of the breast cancer patients.IL17RB/IL17B signaling triggers a substantial increase in the cell growth, proliferation and migration through the activation of NF kappaB as well as the up-regulation of the Bcl-2. In this study we designed carboxymethyl dextran (CMD) Chitosan nanoparticles (ChNPs) to encapsulated IL17RB siRNA and doxorubicin (DOX) as an anticancer drug. Then we investigated the efficiency of the simultaneous delivery of drug/siRNA on viability and gene expression of MDA-MB361 cell lines. Furthermore the efficacy of dual agent nanoparticles to induce apoptosis and inhibit migration of breast cancer cells was assessed by Annexin-V and wound healing assays respectively. Our results showed that DOX-siRNA-CMD-ChNPs had about 114nm size; with polydispersity index and zeta potential about 0.3 and 10.1mV respectively. Fourier transform infrared spectroscopy (FTIR) confirmed the formation of DOX-siRNA-CMD-ChNPs complex. In addition IL17RB siRNA had significant effect on DOX-induced cytotoxicity in MDA MB361 cells. Furthermore treatment with dual agent nanoparticles resulted in a significant silencing of NF-kappaB and Bcl-2 relative gene expression, apoptosis induction and migration inhibition in MDA-MB361 cells. In conclusion, co-delivery of IL17RB siRNA and DOX can be considered as an effective system for the treatment of breast cancer. PMID- 27372408 TI - Postpartum depression symptoms among Amazonian and Northeast Brazilian women. AB - BACKGROUND: Studies analyzing the prevalence of postpartum depression in Brazil have recently increased. However, few studies have examined the Northeast region of Brazil, and no studies have investigated the Amazon region. Therefore, the aim of this study was to investigate postpartum depression in these two regions. METHODS: We administered the Edinburgh Postnatal Depression Scale to a total of 3060 women who used the Brazilian public health system and had given birth between one and three months prior to the interview. A cut-off score >=11 was used to indicate symptoms of postpartum depression. After calculating the prevalence, univariate logistic regressions were performed separately for several possible risk factors (p<0.05). RESULTS: The overall rate of reported symptoms of postpartum depression was 19.5%. The prevalence in the northeast region and Amazon region were 19.0% and 20.3%, respectively (p=0.36). In the univariate logistic regression, low education level (<7 years: p<0.001; 8-10 years: p=0.003), ethnicity (Black: p=0.02; Pardo: p=0.02), few prenatal visits (1 or 2 visits: p=0.04), prenatal care self-assessed as "not very good" (p<0.001) and the prenatal care adequacy index of partially suitable (p=0.01) or not suitable (p<0.001) were identified as significant risk factors for postpartum depression symptoms. LIMITATIONS: Mothers who did not bring their children for immunization. The cross-sectional study does not allow for causality to be established. CONCLUSION: the prevalence rates of postpartum depression were similar to the rates observed for developing countries and higher than the rates observed in developed countries. Based on these findings, we recommend that screening and treatment of pregnant women should be considered a public health priority. PMID- 27372409 TI - Sub-threshold depressive symptoms and brain structure: A magnetic resonance imaging study within the Whitehall II cohort. AB - BACKGROUND: Late-life sub-threshold depressive symptoms (i.e. depressive symptoms that do not meet the criteria for a diagnosis of major depressive disorder) are associated with impaired physical health and function, and increased risk of major depressive disorder. Magnetic resonance imaging (MRI) studies examining late-life major depressive disorder find structural brain changes in grey and white matter. However, the extent to which late-life sub-threshold depression is associated with similar hallmarks is not well established. METHODS: Participants with no history of major depressive disorder were selected from the Whitehall Imaging Sub-Study (n=358, mean age 69+/-5 years, 17% female). Depressive symptoms were measured using the Centre for Epidemiological Studies Depression Scale (CES D) at three previous Whitehall II Study phases (2003-04, 2007-09 and 2012-13) and at the time of the MRI scan (2012-14). The relationships between current and cumulative depressive symptoms and MRI brain measures were explored using Voxel Based Morphometry (VBM) for grey matter and Tract Based Spatial Statistics (TBSS) for white matter. RESULTS: Current sub-threshold depressive symptoms were associated with significant reductions in fractional anisotropy and increases in axial and radial diffusivity. There were no significant relationships between current depressive symptoms and grey matter measures, or cumulative depressive symptoms and MRI measures. LIMITATIONS: The prevalence (10%) of sub-threshold depressive symptoms means that analyses may be underpowered to detect subtle differences in brain structure. CONCLUSIONS: Current sub-threshold depressive symptoms are associated with changes in white matter microstructure, indicating that even mild depressive symptoms are associated with similar MRI hallmarks to those in major depressive disorder. PMID- 27372410 TI - Subsidies to target specialist outreach services into more remote locations: a national cross-sectional study. AB - Objective Targeting rural outreach services to areas of highest relative need is challenging because of the higher costs it imposes on health workers to travel longer distances. This paper studied whether subsidies have the potential to support the provision of specialist outreach services into more remote locations. Methods National data about subsidies for medical specialist outreach providers as part of the Wave 7 Medicine in Australia: Balancing Employment and Life (MABEL) Survey in 2014. Results Nearly half received subsidies: 19% (n=110) from a formal policy, namely the Australian Government Rural Health Outreach Fund (RHOF), and 27% (n=154) from other sources. Subsidised specialists travelled for longer and visited more remote locations relative to the non-subsidised group. In addition, compared with non-subsidised specialists, RHOF-subsidised specialists worked in priority areas and provided equally regular services they intended to continue, despite visiting more remote locations. Conclusion This suggests the RHOF, although limited to one in five specialist outreach providers, is important to increase targeted and stable outreach services in areas of highest relative need. Other subsidies also play a role in facilitating remote service distribution, but may need to be more structured to promote regular, sustained outreach practice. What is known about this topic? There are no studies describing subsidies for specialist doctors to undertake rural outreach work and whether subsidies, including formal and structured subsidies via the Australian Government RHOF, support targeted outreach services compared with no financial support. What does this paper add? Using national data from Australia, we describe subsidisation among specialist outreach providers and show that specialists subsidised via the RHOF or another source are more likely to provide remote outreach services. What are the implications for practitioners? Subsidised specialist outreach providers are more likely to provide remote outreach services. The RHOF, as a formally structured comprehensive subsidy, further targets the provision of priority services into such locations on a regular, ongoing basis. PMID- 27372411 TI - GATA transcription factor as a likely key regulator of the Caenorhabditis elegans innate immune response against gut pathogens. AB - Invertebrate defence against pathogens exclusively relies on components of the innate immune system. Comprehensive information has been collected over the last years on the molecular components of invertebrate immunity and the involved signalling processes, especially for the main invertebrate model species, the fruitfly Drosophila melanogaster and the nematode Caenorhabditis elegans. Yet, the exact regulation of general and specific defences is still not well understood. In the current study, we take advantage of a recently established database, WormExp, which combines all available gene expression studies for C. elegans, in order to explore commonalities and differences in the regulation of nematode immune defence against a large variety of pathogens versus food microbes. We identified significant overlaps in the transcriptional response towards microbes, especially pathogenic bacteria. We also found that the GATA motif is overrepresented in many microbe-induced gene sets and in targets of other previously identified regulators of worm immunity. Moreover, the activated targets of one of the known C. elegans GATA transcription factors, ELT-2, are significantly enriched in the gene sets, which are differentially regulated by gut-infecting pathogens. These findings strongly suggest that GATA transcription factors and particularly ELT-2 play a central role in regulating the C. elegans immune response against gut pathogens. More specific responses to distinct pathogens may be mediated by additional transcription factors, either acting alone or jointly with GATA transcription factors. Taken together, our analysis of the worm's transcriptional response to microbes provides a new perspective on the C. elegans immune system, which we propose to be coordinated by GATA transcription factor ELT-2 in the gut. PMID- 27372412 TI - In situ derivatization-ultrasound-assisted dispersive liquid-liquid microextraction for the determination of neurotransmitters in Parkinson's rat brain microdialysates by ultra high performance liquid chromatography-tandem mass spectrometry. AB - Simultaneous monitoring of several neurotransmitters (NTs) linked to Parkinson's disease (PD) has important scientific significance for PD related pathology, pharmacology and drug screening. A new simple, fast and sensitive analytical method, based on in situ derivatization-ultrasound-assisted dispersive liquid liquid microextraction (in situ DUADLLME) in a single step, has been proposed for the quantitative determination of catecholamines and their biosynthesis precursors and metabolites in rat brain microdialysates. The method involved the rapid injection of the mixture of low toxic bromobenzene (extractant) and acetonitrile (dispersant), which containing commercial Lissamine rhodamine B sulfonyl chloride (LRSC) as derivatization reagent, into the aqueous phase of sample and buffer, and the following in situ DUADLLME procedure. After centrifugation, 50MUL of the sedimented phase (bromobenzene) was directly injected for ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) detection in multiple reaction monitoring (MRM) mode. This interesting combination brought the advantages of speediness, simpleness, low matrix effects and high sensitivity in an effective way. Parameters of in situ DUADLLME and UHPLC-MS/MS conditions were all optimized in detail. The optimum conditions of in situ DUADLLME were found to be 30MUL of microdialysates, 150MUL of acetonitrile containing LRSC, 50MUL of bromobenzene and 800MUL of NaHCO3-Na2CO3 buffer (pH 10.5) for 3.0min at 37 degrees C. Under the optimized conditions, good linearity was observed with LODs (S/N>3) and LOQs (S/N>10) of LRSC derivatized-NTs in the range of 0.002-0.004 and 0.007-0.015 nmol/L, respectively. It also brought good precision (3.2-12.8%, peak area CVs%), accuracy (94.2-108.6%), recovery (94.5-105.5%) and stability (3.8-8.1%, peak area CVs%) results. Moreover, LRSC derivatization significantly improved chromatographic resolution and MS detection sensitivity of NTs when compared with the reported studies through the introduction of a permanent charged moiety from LRSC into NTs. Taken together, this in situ DUADLLME method was successfully applied for the simultaneous determination of six NTs in biological samples. PMID- 27372413 TI - Multinuclear nuclear magnetic resonance spectroscopic and high-performance liquid chromatographic characterization of silica, grafted with specifically deuterated 4-((propylamino)methyl)benzoic acid. AB - Specifically deuterated 4-((propylamino)methyl)benzoic acid-grafted silica (PAMBA silica) was prepared by benzylation of propylamino-grafted silica (PA-silica) by either in situ reduction by sodium cyanoborodeuteride (NaCNBD3) of the Schiff base, formed by the reaction between PA-silica and 4-formylbenzoic acid, or by NaCNBD3 reduction of the isolated Schiff base. The PAMBA-silicas, which contain amine and carboxylic acid functionalities, were characterized by elemental analysis, (13)C, (29)Si, and (2)H solid state NMR, and HPLC. Solid state (13)C NMR revealed that PAMBA-silica prepared by the in situ method consists of di benzylated, mono-benzylated, and unreacted amino-groups while PAMBA-silica prepared by the two-step synthesis consists of only mono-benzylated and unreacted amino-groups. (29)Si solid-state NMR spectra indicated that no significant loss of propylamine groups had occurred during benzylation. Nearly ideal uniaxial rigid-limit (2)H NMR spectra of grafted 4-PAMBA ligands indicates that they form a rigid structure, which provides effective electrostatic screening of inner positive charges when the ligands are in zwitterionic form. HPLC columns packed with PAMBA-silica and PA-silica were evaluated for ionic solutes at different pH of the mobile phase. Retention times increased for cations and decreased for anions at increasing pH. These trends show that PAMBA-silicas act as cation and anion exchangers at high and low pH, respectively. The pKa values of grafted carboxylic acid, determined from HPLC of weakly retaining solutes, are close to pKa of the solution PAMBA. PMID- 27372414 TI - Comprehensive two-dimensional liquid chromatography-tandem mass spectrometry for the simultaneous determination of wine polyphenols and target contaminants. AB - A novel system for comprehensive two-dimensional liquid chromatography coupled to a triple quadrupole mass spectrometer is described for the analysis of wine components. The first dimension consisted of a 250-mm microbore cyano column utilizing 5MUm diameter particles, interfaced to a 50-mm superficially-porous particle C18 column with 2.7MUm diameter particles. Both columns were operated under reversed-phase conditions. Correlation between the two chromatographic separation modes was decreased by designing a 60-s shift gradient program in the second dimension, and the increase in orthogonality was evaluated quantitatively utilizing a number of orthogonality metrics. The system was employed for the analysis of a red wine sample, without preliminary clean-up procedures, and a total of 43 polyphenols were separated and identified. Comparison with a one dimensional LC system showed a large increase in the number of identified components with the two-dimensional system. Optimized multiple reaction monitoring experiments allowed for the determination of trans-resveratrol, which is one of the most active antioxidant component of wine, and for monuron, a plant protection product (herbicide) of interest to regulatory agencies. The estimated limits of detection and of quantification were 0.3MUgL(-1) and 1MUgL(-1), respectively, well below the minimum detection limit (10MUgL(-1)) set by current regulation. PMID- 27372415 TI - Optimization of a single phase method for lipid extraction from milk. AB - For LC-MS-based lipidomic analysis of milk, total lipid extraction from raw milk is generally conducted with Folch or Bligh and Dyer methods; both methods are based on two-phase partition of lipids, and thus time-consuming. In this work, three solvent systems for one-phase extraction of milk lipids were compared with the standard Folch method. Two of the solvent systems (butanol/methanol, 3:1 and 1:1) previously tested for lipid extraction from plasma were found to provide adequate extraction for polar lipids, but incomplete extraction for triglycerides, especially highly lipophilic species. By contrast, our newly designed solvent mix composed of butanol, methanol and chloroform (at a 3:5:4 ratio) provided similar extraction efficiency for triglycerides and higher yield for some of the phospholipids, as compared to the Folch method. This new one phase extraction method is very simple yet comprehensive and thus suitable for high throughput lipid analysis of milk samples. PMID- 27372416 TI - Enantioselective extraction of phenylsuccinic acid in aqueous two-phase systems based on acetone and beta-cyclodextrin derivative: Modeling and optimization through response surface methodology. AB - A novel aqueous two-phase system (ATPS) composed of beta-cyclodextrin (beta-CD) derivative and acetone was developed for enantioselective extraction of racemic phenylsuccinic acid (PSA). Binodal curves, tie-lines, and critical points for the investigated ATPS were determined and the experimental tie-lines data were successfully correlated by Othmer-Tobias, Bancroft, and Setschenow-type equations. ATPS containing sulfobutyl ether-beta-CD (SBE-beta-CD) exhibited better enantioselectivity than that using carboxymethyl-beta-CD (CM-beta-CD). To optimize enantioselective partitioning conditions of PSA in acetone/SBE-beta-CD ATPS, three factors (PSA concentration, pH, and equilibrium temperature) were analyzed by using central composite design in response surface methodology. The calculated equilibrium constants of inclusion complexation are 1638.64M-1 for SBE beta-CD-(R)-PSA and 835.84M-1 for SBE-beta-CD-(S)-PSA, respectively. Under the optimized conditions, the separation factor of 3.14 and high enrichment efficiency (ER=98.06%, ES=99.25%) were simultaneously achieved in a single step. PMID- 27372417 TI - Enantiomeric separation of non-protein amino acids by electrokinetic chromatography. AB - New analytical methodologies enabling the enantiomeric separation of a group of non-protein amino acids of interest in the pharmaceutical and food analysis fields were developed in this work using Electrokinetic Chromatography. The use of FMOC as derivatization reagent and the subsequent separation using acidic conditions (formate buffer at pH 2.0) and anionic cyclodextrins as chiral selectors allowed the chiral separation of eight from the ten non-protein amino acids studied. Pyroglutamic acid, norvaline, norleucine, 3,4 dihydroxyphenilalanine, 2-aminoadipic acid, and selenomethionine were enantiomericaly separated using sulfated-alpha-CD while sulfated-gamma-CD enabled the enantiomeric separation of norvaline, 3,4-dihydroxyphenilalanine, 2 aminoadipic acid, selenomethionie, citrulline, and pipecolic acid. Moreover, the potential of the developed methodologies was demonstrated in the analysis of citrulline and its enantiomeric impurity in food supplements. For that purpose, experimental and instrumental variables were optimized and the analytical characteristics of the proposed method were evaluated. LODs of 2.1*10-7 and 1.8*10-7M for d- and l-citrulline, respectively, were obtained. d-Cit was not detectable in any of the six food supplement samples analyzed showing that the effect of storage time on the racemization of citrulline was negligible. PMID- 27372418 TI - Obesity conveys poor outcome in patients with hepatocellular carcinoma treated by transarterial chemoembolization. AB - PURPOSE: The purpose of this retrospective study was to evaluate the impact of obesity on radiologic outcomes in patients with hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). MATERIALS AND METHODS: A total of 100 TACE procedures performed in 57 patients (42 men, 15 women) with a mean age of 62 years+/-8.4 (SD) (range: 39-83 years) were retrospectively reviewed. The 1-2-month follow-up computed tomography or magnetic resonance imaging examinations was assessed for new or residual disease and radiologic response using mRECIST criteria. Patients were categorized into two groups according to body mass index (BMI). Patients with BMI<25kg/m2 were further referred as to low BMI patients and those with BMI>=25kg/m2 as high BMI patients. Outcomes were compared between the two groups. RESULTS: Low and high BMI patients were similar in regard to age, gender, HCC etiology and stage, and pre-procedure disease burden. TACE for high BMI, compared to low BMI, patients resulted in lower complete response (39% vs. 66%) and higher progressive disease (21% vs. 5%) rates (P=0.04), and higher rates of residual disease (63% vs. 39%, P=0.02) and new lesions in untreated liver (39% vs. 18%, P=0.04) on 1-2-month follow-up imaging. CONCLUSIONS: High BMI is associated with significantly more residual disease, new lesions, and progressive disease in patients with HCC treated by TACE. PMID- 27372419 TI - Educational Attainment and Gestational Weight Gain among U.S. Mothers. AB - BACKGROUND: Education is an important social determinant of many health outcomes, but the relationship between educational attainment and the amount of weight gained over the course of a woman's pregnancy (gestational weight gain [GWG]) has not been established clearly. METHODS: We used data from 1979 through 2010 for women in the National Longitudinal Survey of Youth (1979) cohort (n = 6,344 pregnancies from 2,769 women). We used generalized estimating equations to estimate the association between educational attainment and GWG adequacy (as defined by 2009 Institute of Medicine guidelines), controlling for diverse social factors from across the life course (e.g., income, wealth, educational aspirations and expectations) and considering effect measure modification by race/ethnicity and prepregnancy overweight status. RESULTS: In most cases, women with more education had increased odds of gaining a recommended amount of gestational weight, independent of educational aspirations and educational expectations and relatively robust to sensitivity analyses. This trend manifested itself in a few different ways. Those with less education had higher odds of inadequate GWG than those with more education. Among those who were not overweight before pregnancy, those with less education had higher odds of excessive GWG than college graduates. Among women who were White, those with less than a high school degree had higher odds of excessive GWG than those with more education. CONCLUSION: The relationship between educational attainment and GWG is nuanced and nonlinear. PMID- 27372420 TI - An Examination of Victim, Assailant, and Assault Characteristics among Cases Classified as Predatory Drug-Facilitated Sexual Assault. AB - INTRODUCTION: Drug-facilitated sexual assault (DFSA) can be characterized as predatory, where the survivor is covertly or forcibly administered an incapacitating or disinhibiting drug. The purpose of our study was to determine what factors, if any, are associated with cases classified as predatory DFSA. METHODS: Cases were classified on toxicological testing as predatory where there was an unexpected drug(s) found and non-predatory where a drug(s) found had been voluntarily consumed or no drugs at all were found in collected urine samples. RESULTS: One hundred eighty-four suspected intentional drugging cases were seen at one of seven participating hospital-based sexual assault treatment centers. Urine specimens were analyzed from 178 of these cases, of which 48.9% were classified as predatory. In a logistic regression model, the odds of having experienced a predatory DFSA were lower if the survivor was a student or assaulted by a single assailant, but higher if the survivor self-reported mental health problems in the previous 6 months or that the mode of suspected drugging was a recreational drug or non-alcoholic drink (versus an alcoholic drink). CONCLUSIONS: These differences in survivor, assailant, and assault characteristics between cases classified as predatory and non-predatory DFSAs may have important implications for intervention and prevention. PMID- 27372421 TI - In situ diselenide-crosslinked polymeric micelles for ROS-mediated anticancer drug delivery. AB - Stimuli-responsive micelles have emerged as the drug carrier for cancer therapy since they can exclusively release the drug via their structural changes in response to the specific stimuli of the target site. Herein, we developed the in situ diselenide-crosslinked micelles (DCMs), which are responsive to the abnormal ROS levels of tumoral region, as anticancer drug carriers. The DCMs were spontaneously derived from selenol-bearing triblock copolymers consisting of polyethylene glycol (PEG) and polypeptide derivatives. During micelle formation, doxorubicine (DOX) was effectively encapsulated in the hydrophobic core, and diselenide crosslinks were formed in the shell. The DCMs maintained their structural integrity, at least for 6 days in physiological conditions, even in the presence of destabilizing agents. However, ROS-rich conditions triggered rapid release of DOX from the DOX-encapsulating DCMs (DOX-DCMs) because the hydrophobic diselenide bond was cleaved into hydrophilic selenic acid derivatives. Interestingly, after their systemic administration into the tumor bearing mice, DOX-DCMs delivered significantly more drug to tumors (1.69-fold and 3.73-fold higher amount compared with their non-crosslinked counterparts and free drug, respectively) and effectively suppressed tumor growth. Overall, our data indicate that DCMs have great potential as drug carriers for anticancer therapy. PMID- 27372422 TI - The fluorescent bioprobe with aggregation-induced emission features for monitoring to carbon dioxide generation rate in single living cell and early identification of cancer cells. AB - A novel fluorescent probe, tris (2-(dimethylamino) ethyl)-4,4',4"-(1H-pyrrole 1,2,5-triyl) tribenzoate (TPP-TMAE), with aggregation-enhanced emission (AEE) feature showed a simple, highly selective, specific, and instant response to trace amount carbon dioxide (CO2). Because of this special characteristic, TPP TMAE is ideal to be a biomarker for in-situ monitoring of the CO2 generation rate during the metabolism of single living cell. The rates in single living HeLa cell, MCF-7 cell, and MEF cell were 6.40 * 10(-6)+/-6.0 * 10(-8) MUg/h, 5.78 * 10(-6)+/-6.0 * 10(-8) MUg/h, and 4.27 * 10(-7)+/-4.0 * 10(-9) MUg/h, respectively. The distinct responses of TPP-TMAE to CO2 generated from cancer cells and normal cells suggested TPP-TMAE as a useful tool for deeper understanding metabolism process and distinguishing cancer cells from normal cells during the early diagnosis of cancers. PMID- 27372423 TI - Laminin-511 and laminin-521-based matrices for efficient hepatic specification of human pluripotent stem cells. AB - Human pluripotent stem cells (hPSCs) have gained a solid foothold in basic research and drug industry as they can be used in vitro to study human development and have potential to offer limitless supply of various somatic cell types needed in drug development. Although the hepatic differentiation of hPSCs has been extensively studied, only a little attention has been paid to the role of the extracellular matrix. In this study we used laminin-511, laminin-521, and fibronectin, found in human liver progenitor cells, as culture matrices for hPSC derived definitive endoderm cells. We observed that laminin-511 and laminin-521 either alone or in combination support the hepatic specification and that fibronectin is not a vital matrix protein for the hPSC-derived definitive endoderm cells. The expression of the laminin-511/521-specific integrins increased during the definitive endoderm induction and hepatic specification. The hepatic cells differentiated on laminin matrices showed the upregulation of liver specific markers both at mRNA and protein levels, secreted human albumin, stored glycogen, and exhibited cytochrome P450 enzyme activity and inducibility. Altogether, we found that laminin-511 and laminin-521 can be used as stage specific matrices to guide the hepatic specification of hPSC-derived definitive endoderm cells. PMID- 27372424 TI - Cathepsin S-cleavable, multi-block HPMA copolymers for improved SPECT/CT imaging of pancreatic cancer. AB - This work continues our efforts to improve the diagnostic and radiotherapeutic effectiveness of nanomedicine platforms by developing approaches to reduce the non-target accumulation of these agents. Herein, we developed multi-block HPMA copolymers with backbones that are susceptible to cleavage by cathepsin S, a protease that is abundantly expressed in tissues of the mononuclear phagocyte system (MPS). Specifically, a bis-thiol terminated HPMA telechelic copolymer containing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Three maleimide modified linkers with different sequences, including cathepsin S degradable oligopeptide, scramble oligopeptide and oligo ethylene glycol, were subsequently synthesized and used for the extension of the HPMA copolymers by thiol-maleimide click chemistry. All multi-block HPMA copolymers could be labeled by (177)Lu with high labeling efficiency and exhibited high serum stability. In vitro cleavage studies demonstrated highly selective and efficient cathepsin S mediated cleavage of the cathepsin S susceptible multi-block HPMA copolymer. A modified multi-block HPMA copolymer series capable of Forster Resonance Energy Transfer (FRET) was utilized to investigate the rate of cleavage of the multi-block HPMA copolymers in monocyte derived macrophages. Confocal imaging and flow cytometry studies revealed substantially higher rates of cleavage for the multi-block HPMA copolymers containing the cathepsin S-susceptible linker. The efficacy of the cathepsin S cleavable multi-block HPMA copolymer was further examined using an in vivo model of pancreatic ductal adenocarcinoma. Based on the biodistribution and SPECT/CT studies, the copolymer extended with the cathepsin S susceptible linker exhibited significantly faster clearance and lower non-target retention without compromising tumor targeting. Overall, these results indicate that exploitation of the cathepsin S activity in MPS tissues can be utilized to substantially lower non-target accumulation, suggesting this is a promising approach for the development of diagnostic and radiotherapeutic nanomedicine platforms. PMID- 27372425 TI - Dispensability of a sulfolipid for photoautotrophic cell growth and photosynthesis in a marine cyanobacterium, Synechococcus sp. PCC 7002. AB - Sulfoquinovosyl diacylglycerol, which mainly comprises thylakoid membranes in oxygenic photosynthetic organisms, plays species-dependent roles in freshwater microbes. In this study, a sulfoquinovosyl-diacylglycerol deficient mutant was generated in a cyanobacterium, Synechococcus sp. PCC 7002, for the first time among marine microbes to gain more insight into its physiological significance. The mutation had little deleterious impact on photoautotrophic cell growth, and functional and structural properties of the photosystem II complex. These findings were similar to previous observations for a freshwater cyanobacterium, Synechococcus elongatus PCC 7942, but were distinct from those for another freshwater cyanobacterium, Synechocystis sp. PCC 6803, and a green alga, Chlamydomonas reinhardtii, both of which require sulfoquinovosyl diacylglycerol for cell growth and/or photosystem II. Therefore, the functionality of PSII to dispense with sulfoquinovosyl diacylglycerol in Synechococcus sp. PCC 7002, similar to that in Synechococcus elongatus PCC 7942, seemed to have been excluded from the evolution of the PSII complex from cyanobacteria to green algal chloroplasts. Meanwhile, sulfoquinovosyl diacylglycerol was found to contribute to photoheterotrophic growth of Synechococcus sp. PCC 7002, which revealed a novel species-dependent strategy for utilizing SQDG in physiological processes. PMID- 27372426 TI - WITHDRAWN: Chronic intermittent hypobaric hypoxia attenuates radiation-induced heart damage in rats. PMID- 27372427 TI - Arabidopsis COP1-interacting protein 1 is a positive regulator of ABA response. AB - COP1-interacting protein 1 (CIP1, At5g41790) was the first reported interacting protein for CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) of Arabidopsis; however its physiological function has remained unknown for two decades. Here we show that CIP1 is a positive regulator of abscisic acid (ABA) response. CIP1 is mainly expressed in the photosynthetic cells and the vascular tissue, and its promoter activity can be induced by osmotic stress and ABA. The CIP1 protein is localized to the plasma membrane. A T-DNA insertion mutant cip1-1 was then characterized. The mutant is sensitive to osmotic stress and has ABA insensitive phenotypes. RNA sequencing showed that cip1-1 has lower levels of gene expression in abiotic stress response compared with the wild-type. Meanwhile, transcript levels of ABA biosynthesis genes are higher in cip1-1 than in the wild-type. These results suggested that CIP1 is positively involved in ABA response. PMID- 27372428 TI - Spironolactone and glucose metabolism, a systematic review and meta-analysis of randomized controlled trials. AB - Diabetes predicts cardiovascular disease (CVD); some drugs are effective for CVD prevention but increase the risk of diabetes. In a systematic review and meta analysis of placebo-controlled trials, we assessed if spironolactone, a mineralocorticoid receptor antagonist, affected glycemic control. We searched PubMed using ("spironolactone" or "aldactone") and trial and ("glucose" or "diabetes" or "insulin" or "insulin resistance") until January 4, 2016. In total, 18 eligible trials were identified; 10 on fasting glucose, 8 on hemoglobin A1c (HbA1c), 7 on homeostatic model assessment (HOMA)-insulin resistance (IR), and 8 on insulin. Spironolactone increased HbA1c (0.16%, 95% confidence interval 0.02 to 0.30) but had no clear effect on fasting glucose, HOMA-IR, and insulin. A mechanistic randomized controlled trial in people with and without diabetes might provide insight concerning these pleiotropic effects on diabetes and CVD relevant to prevention of both diseases. PMID- 27372429 TI - Initial Results and Long-Term Follow-up of Percutaneous Mitral Valvuloplasty in Patients with Pulmonary Hypertension. AB - BACKGROUND: Percutaneous balloon mitral valvuloplasty (PMV) is an attractive therapeutic approach in patients with mitral stenosis. The aim of this study was to assess the immediate and long-term clinical, echocardiographic and haemodynamic outcomes of PMV in patients with severe pulmonary hypertension (PAH). METHODS: Percutaneous balloon mitral valvuloplasty was performed in 157 consecutive patients; 60 patients (38.2%) had significant PAH defined as baseline pulmonary artery mean pressure (PAMP) >= 30mm Hg (Group 1) and 97 patients (61.8%) had PAMP <= 30mmHg (Group 2). Pulmonary artery systolic pressure (PASP), mortality, need for mitral valve replacement or new PMV, and valve restenosis were evaluated during follow-up. RESULTS: Mean age was 44.2 years and 88.5% (139 patients) were women. Primary success was achieved in 79.6% of the patients (125 patients) without differences between the groups. Mitral valve area increased from 0.90cm2 to 1.76cm2, PASP fell from 57mmHg to 35mmHg in Group 1 and from 38mmHg to 30mmHg in Group 2. Median PASP in Group 1 was 35, 32, 36, 38 and 34mmHg at 12, 24, 36, 48 and 60 months. There were no significant differences in mitral valve area, PASP and clinical status between the groups. CONCLUSION: Percutaneous balloon mitral valvuloplasty is a safe and effective technique for the treatment of patients with mitral stenosis and PAH. A significant decrease in pulmonary pressure was observed after valvuloplasty. Although there was a gradual decrease of MVA at long-term follow-up, most patients remained asymptomatic and PASP was stable. PMID- 27372430 TI - Iron Deficiency in COPD Associates with Increased Pulmonary Artery Pressure Estimated by Echocardiography. AB - OBJECTIVES: Iron deficiency (ID) might augment chronic pulmonary hypertension in chronic obstructive pulmonary disease (COPD). This observational study investigates the association between ID and systolic pulmonary artery pressure estimated by echocardiography in non-anaemic COPD outpatients. METHODS: Non anaemic COPD patients (GOLD II-IV) with no history of cardiovascular disease were recruited from outpatient clinics. Iron deficiency was defined as ferritin<100MUg/L. Pulmonary artery pressure was estimated from the tricuspid regurgitation maximum velocity (TR Vmax). Tricuspid regurgitation Vmax indicative of pulmonary hypertension was considered present for values >= 2.9 m/s. RESULTS: In a total of 75 included patients, 31 (41%) had ID. These patients had a significantly higher TR Vmax (3.02 vs. 2.77 m/s, p=0.01) and lower diffusion capacity of carbon monoxide (40% vs. 50% of predicted, p<0.01), though similar in age, sex, pack years, FEV1 and high-sensitive CRP (p>0.05). Ferritin inversely correlated with TR Vmax in ID patients (-0.37 (p=0.04)). The prevalence of TR Vmax >= 2.9 m/s was twice as high in patients with ID (58% vs. 29%) and odds ratio of pulmonary hypertension in ID (compared to no ID) was 3.3 (95% CI 1.3 8.6, p=0.015). CONCLUSION: Iron deficiency in non-anaemic COPD patients was associated with a modest increase in systolic pulmonary artery pressure and limitation of diffusion capacity. PMID- 27372431 TI - Increment of HFABP Level in Coronary Artery In-Stent Restenosis Segments in Diabetic and Nondiabetic Minipigs: HFABP Overexpression Promotes Multiple Pathway Related Inflammation, Growth and Migration in Human Vascular Smooth Muscle Cells. AB - BACKGROUND: Our previous study suggested that heart-type fatty acid-binding protein (HFABP) levels were greatly elevated in the conditioned medium of explant culture of in-stent restenosis (ISR) tissue from diabetic minipigs compared with those of non-ISR tissue. We here verified this result in animal tissues and investigated the impact of HFABP overexpression in human aortic smooth muscle cells (hASMCs). METHODS AND RESULTS: In Western blot and real-time RT-PCR, HFABP protein and mRNA levels were significantly higher in ISR than in non-ISR tissues from minipigs, and higher in the ISR tissue from diabetic minipigs than that from nondiabetic minipigs. The mRNA microarray and cellular effects of hASMC retroviral overexpression of HFABP and vector was analyzed. Compared with vector, HFABP transduction activates multiple signaling pathways (e.g. adipokine, TGF beta, Toll-like receptor, Wnt, Hedgehog, ErbB and Notch) and promotes inflammation, growth and migration in hASMCs whereas the knockdown of HFABP by small hairpin RNA attenuates these effects. CONCLUSION: HFABP expression is significantly higher in ISR tissue than in non-ISR tissue from diabetic and nondiabetic minipigs. Overexpression of HFABP induces multiple pathway-related promotion of inflammation, growth and migration in vascular SMCs, suggesting a potential role in coronary artery ISR. PMID- 27372432 TI - Selective COX-2 Inhibition Exerts No Negative Effects on Peripheral Blood Lymphocytes in Allergic Asthmatics. AB - BACKGROUND: Selective inhibition of cyclooxygenase-2 (COX-2) reduces the production of prostaglandin E2 (PGE2), which can have both pro- and anti inflammatory effects on allergic inflammation. Moreover, in vitro PGE2 has been shown to affect inflammation through the modulation of lymphocyte responses. METHODS: Sixteen subjects with mild allergic asthma were recruited to a two period cross-over study: one treatment period with the selective COX-2 inhibitor etoricoxib and one without. Each treatment period ended with an airway challenge with the patient's relevant allergen. Antigen-specific proliferation with the major cat allergen, Fel d 1, was analysed in PBMCs. CD4+ T cells were phenotyped using flow cytometry, and mRNA expression of FOXP3 in anti-CD3-stimulated CD4+ cells were analysed. RESULTS: No significant impact of in vivo inhibition of COX 2 was detected on the proportion of Th1, Th2, or Treg cells in peripheral blood. Likewise, the treatment had minor effects on the stimulated expression of FOXP3 mRNA in CD4+ T cells. Proliferation of PBMCs to the major cat allergen Fel d 1 was slightly reduced by etoricoxib treatment in cat-allergic patients. CONCLUSIONS: Short-term treatment with the COX-2 inhibitor etoricoxib had a minor impact on T-cell responses, supporting its safe use also in subjects exposed to triggers of lymphocyte activation. PMID- 27372433 TI - The Patient Participation Culture Tool for healthcare workers (PaCT-HCW) on general hospital wards: A development and psychometric validation study. AB - BACKGROUND: Patient participation is an important subject for modern healthcare. In order to improve patient participation on a ward, the ward's culture regarding patient participation should first be measured. In this study a measurement tool for patient participation culture from the healthcare worker's perspective, the Patient Participation Culture Tool for healthcare workers (PaCT-HCW), was developed and psychometrically evaluated. OBJECTIVES: The aim of this study was to develop and validate a tool that measures the healthcare worker-related factors of patient participation and information sharing and dialogue in patient participation from the healthcare worker's perspective in order to represent the patient participation culture on general and university hospital wards. DESIGN: A four-phased validation study was conducted: (1) defining the construct of the PaCT-HCW, (2) development of the PaCT-HCW, (3) content validation, and (4) psychometric evaluation. SETTINGS: The Belgian Federal Government invited all Flemish general and university hospitals by e-mail to distribute the PaCT-HCW in their organization. Fifteen general hospitals took part in the study. PARTICIPANTS: Units for surgery, general medicine, medical rehabilitation, geriatric and maternal care were included. Intensive care-units, emergency room units, psychiatric units and units with no admitted patients (e.g. radiology) were excluded. The respondents had to be caregivers, with hands-on patient contact, who worked on the same ward for more than six months. Nursing students and other healthcare workers with short-time internship on the ward were excluded. The tool was completed by 1329 respondents on 163 wards. METHODS: The PaCT-HCW was psychometrically evaluated by use of an exploratory factor analysis and calculation of the internal consistency. RESULTS: A model containing eight components was developed through a literature review, individual interviews, and focus interviews. The developed model showed high sampling adequacy and the Bartlett's test of sphericity was significant. An exploratory factor analysis identified eight components, explaining 49.88% of the variances. The eight original included components were retained. The PaCT-HCW also showed high internal consistency. CONCLUSION: The PaCT-HCW offers an in-depth and differentiated perspective of the healthcare worker-related factors of patient participation and information sharing and dialogue in patient participation. The PaCT-HCW has been developed thoroughly, resulting in a strong, psychometric evaluated tool and is a valuable measure for both scientists and clinicians to measure these two aspects in general and university hospitals. By using the PaCT HCW, the opportunity is created to develop specific actions to improve patient participation. PMID- 27372434 TI - Comparison of the effects of lidocaine pre-administration and local warming of the intravenous access site on propofol injection pain: Randomized, double-blind controlled trial. AB - BACKGROUND: Lidocaine reduces pain that occurs upon the intravenous injection of propofol. But, there are few non-pharmacological nursing interventions to reduce propofol injection pain. OBJECTIVE: To compare the effects of lidocaine pre administration and local warming of the intravenous access site on propofol injection pain. DESIGN: Prospective, double-blind, randomized controlled trial. SETTING: The 555 bed, non-teaching National Cancer Center in Kyunggido, South Korea. PARTICIPANTS: A total of 96 patients who underwent thyroidectomy under total intravenous general anesthesia with propofol were randomly allocated to the control, lidocaine pre-administration (LA) or local warming (LW) group. METHODS: All three groups received 2% propofol with an effect-site target at 3MUg/mL for induction dose. The control group received 2% propofol with no intervention. The lidocaine pre-administration group received 2% propofol 30s after 1% lidocaine 30mg. The local warming group received 2% propofol after warming of the intravenous access site for 1min using 43 degrees C forced air. Propofol injection pain was assessed by four-point verbal categorial scoring (VCS), numerical rating scale (NRS) and surgical pleth index (SPI). RESULTS: Pain VCS of the LA group (mean+/-SD, 1.11+/-0.45) was significantly reduced (U=-3.92, p<.001) compared to the control group (mean+/-SD, 1.71+/-0.74). Pain VCS of the LW group (mean+/-SD, 0.76+/-0.44) was significantly reduced (U=-5.17, p<.001) compared to the control group (mean+/-SD, 1.71+/-0.74). Pain VCS of the LW group was significantly reduced compared to the LA group (U=-3.33, p=.001]. Pain NRS of the LA group (mean+/-SD, 4.31+/-2.32) was significantly reduced (mean difference, 1.82; 95% CI, 0.63-3.00; p=.003) compared to the control group (mean+/-SD, 6.13+/ 2.39). Pain NRS of the LW group (mean+/-SD, 3.06+/-2.37) was significantly reduced (mean difference, 3.07; 95% CI, 1.63-4.51; p<.009) compared to the control group. There were significant differences in pain NRS between the LA group and the LW group (mean difference, 1.25; 95% CI, 0.09-2.42; p=.035). SPI of the LA group (mean+/-SD, 64.1+/-16.3) was significantly reduced (mean difference control versus LA, 8.36; 95% CI, 1.64-15.1; p=.016) compared to the control group (mean+/-SD, 72.5+/-9.56). SPI of the LW group (mean+/-SD, 55.0+/-16.2) was significantly reduced (mean difference control versus LW, 17.4; 95% CI, 10.8 24.0; p<.001) compared to the control group. There was a significant difference in SPI between the LA group and LW group (mean difference, 9.06; 95% CI, 1.02 17.1; p=.028). CONCLUSION: Local warming of the intravenous access site by 43 degrees C forced air for 1min is slightly more effective in reducing propofol injection pain compared to lidocaine pre-administration. PMID- 27372435 TI - Radical formation in the FMN-photosensitized reactions of unsaturated fatty acids bearing double bonds at different positions. AB - Although the reaction mechanisms through which flavin mononucleotide works as an endogenous photosensitizer have been investigated (Baier et al., 2006; Edwards and Silva, 2001; Pajares et al., 2001; Criado et al., 2003; Massad et al., 2008) [23-27], few studies have been performed for the reactions of flavin mononucleotide with unsaturated fatty acids. To examine the reactions of flavin mononucleotide with unsaturated fatty acids bearing a double bond at different positions, an electron spin resonance, a high performance liquid chromatography electron spin resonance and a high performance liquid chromatography-electron spin resonance-mass spectrometry were employed. The control reaction mixtures contained 25MUmolL(-1) of flavin mononucleotide, 1.0mmolL(-1) of FeSO4(NH4)2SO4, 10mmolL(-1) of cholic acid, 30mmolL(-1) of phosphate buffer (pH 7.4) and 0.1molL( 1) of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone in deuterium oxide. In addition, it also contained 4.3mmolL(-1) of one of the following: (z)-11 octadecenoic acid, (z)-6-octadecenoic acid, (z)-9-octadecenoic acid or (z, z)-9, 12-octadecadienoic acid. The control reaction mixtures without FeSO4(NH4)2SO4 and alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone were exposed to the visible light at 436nm (7.8Jcm(-2)). After the irradiation, alpha-(4-pyridyl-1-oxide)-N-tert butylnitrone was added. The reactions started from adding FeSO4(NH4)2SO4 and performed at 25 degrees C for 1min. Electron spin resonance measurements of the control reaction mixtures showed prominent signals (alpha(N)=1.58mT and alpha(Hbeta)=0.26mT). High performance liquid chromatography-electron spin resonance analyses of the control reaction mixtures showed prominent peaks at the retention times of 31.1min {(z)-6-octadecenoic acid}, 39.6min {(z)-9-octadecenoic acid}, 44.9min {(z)-11-octadecenoic acid} and 40.2min {(z, z)-9, 12 octadecadienoic acid}. High performance liquid chromatography-electron spin resonance-mass analyses of the control reaction mixtures showed that 4 carboxybutyl, 7-carboxyheptyl and 9-carboxynonyl radicals formed in the control reaction mixtures of (z)-6-octadecenoic acid, (z)-9-octadecenoic acid {or (z, z) 9,12-octadecadienoic acid} and (z)-11-octadecenoic acid, respectively. The 4 carboxybutyl, 7-carboxyheptyl and 9-carboxynonyl radicals are all generated through beta-scission of alkoxy radicals formed on carboxyl ends of the double bonds of the unsaturated fatty acids. Thus, we could reveal reactive sites of unsaturated fatty acids in the photosensitized reaction of flavin mononucleotide with unsaturated fatty acids bearing a double bond at different positions. PMID- 27372436 TI - Impact of sleep quality on the quality of life of patients with Parkinson's disease: a questionnaire based study. AB - OBJECTIVE: Poor sleep quality contributes to the inferior quality of life of patients with Parkinson's disease (PD) despite appropriate treatment of motor symptoms. The literature about the impact of sleep quality on quality of life of patients with PD is as yet sparse. MATERIAL AND METHODS: One hundred patients of PD diagnosed as per UK Brain Bank criteria were assessed for severity and stage of PD using UPDRS and modified Hoehn &Yahr scales. The quality of sleep was assessed by Pittsburgh Sleep Quality Index and excessive daytime somnolence (EDS) was evaluated using Epworth Sleepiness Scale. Parkinson's Disease Questionnaire 39 (PDQ-39) was used to determine quality of life of the patients. Comorbid depression and anxiety were assessed using Inventory of Depressive Symptoms-Self Rated and Hamilton Anxiety Rating Scale. Pearson's correlation and multiple linear regressions were used to analyze relation of sleep quality with quality of life of patients. RESULTS: Fifty patients had poor sleep quality. EDS was present in only 9 patients. Co-morbid depression and anxiety were present in 52 and 34 patients respectively. While the motor severity assessed by UPDRS-III was observed to adversely affect quality of life, it did not negatively impact quality of sleep. Higher score on UPDRS-total and UPDRS IV suggesting advanced disease correlated with poor sleep quality. Depression and anxiety were significantly more frequent in patients with poor sleep quality (p<0.01). Patients with poor sleep quality had worse quality of life (r=0.338, p<0.05). Depression and anxiety were also observed to have significant negative impact on quality of life of PD patients (p<0.01). Poor sleep quality was not found to be an independent predictor of quality of life using multiple linear regression analysis. CONCLUSION: Poor sleep quality along with comorbid depression, anxiety and advanced stage of disease is associated with poor quality of life. PMID- 27372437 TI - Predictors of outcomes of psychological treatments for disordered gambling: A systematic review. AB - This systematic review aimed to synthesise the evidence relating to pre-treatment predictors of gambling outcomes following psychological treatment for disordered gambling across multiple time-points (i.e., post-treatment, short-term, medium term, and long-term). A systematic search from 1990 to 2016 identified 50 articles, from which 11 socio-demographic, 16 gambling-related, 21 psychological/psychosocial, 12 treatment, and no therapist-related variables, were identified. Male gender and low depression levels were the most consistent predictors of successful treatment outcomes across multiple time-points. Likely predictors of successful treatment outcomes also included older age, lower gambling symptom severity, lower levels of gambling behaviours and alcohol use, and higher treatment session attendance. Significant associations, at a minimum of one time-point, were identified between successful treatment outcomes and being employed, ethnicity, no gambling debt, personality traits and being in the action stage of change. Mixed results were identified for treatment goal, while education, income, preferred gambling activity, problem gambling duration, anxiety, any psychiatric comorbidity, psychological distress, substance use, prior gambling treatment and medication use were not significantly associated with treatment outcomes at any time-point. Further research involving consistent treatment outcome frameworks, examination of treatment and therapist predictor variables, and evaluation of predictors across long-term follow-ups is warranted to advance this developing field of research. PMID- 27372438 TI - The relationship between bupropion and suicide in post-mortem investigations. AB - We reviewed the 33727 postmortem toxicology investigations performed in Finland over a period of 5years (2009-2013) and identified those in which the antidepressant bupropion was detected. Cases positive for other antidepressant drugs were reviewed for comparison. The postmortem toxicological examination included, in all cases, the routine screening and quantification of hundreds of drugs and poisons using quality-controlled methods. Bupropion was detected in 65 cases. A large proportion of the bupropion-positive deaths resulted from suicide (55%). In fatal poisoning cases found positive for bupropion, the proportion of suicide was even higher (77%). The measured median bupropion postmortem blood concentration (0.69mg/L) was markedly higher than the normal therapeutic range in plasma in the treatment of depression (up to 0.1mg/L) and even higher in fatal bupropion poisonings (13mg/L). Only 14% of the deceased positive for bupropion were estimated to be drug abusers. However, nearly all of the drug abuse cases were from the last year of the study (2013), indicating a recent increase of the use of bupropion among drug abusers and possibly even abuse of bupropion itself. Suicide victims positive for bupropion were younger than those who died with other antidepressant drugs in their blood. In addition, the percentage of fatal poisonings among bupropion-positive postmortem cases was higher than among the users of other antidepressant drugs. Suicide was significantly more common among the deceased positive for bupropion than among users of other antidepressant drugs. An unknown degree of bupropion degradation before the assay and post mortem redistribution of bupropion may have impacted the measured levels. Nonetheless, all post-mortem concentrations of bupropion were elevated and especially high concentrations were detected in suicides. PMID- 27372439 TI - Re: 'Long-term Mortality in Patients with Asymptomatic Carotid Stenosis: Implications for Statin Therapy'. PMID- 27372440 TI - Not all minds wander equally: The influence of traits, states and road environment factors on self-reported mind wandering during everyday driving. AB - Inattention is a road safety problem, but few studies have focused specifically on mind wandering during everyday driving. This paper explores differences in self-reported mind wandering according to driver demographic characteristics (including age and gender), cognitive traits (such as tendency toward cognitive failure or mindful attention), states (such as feeling tired or stressed) and road environment factors (such as route familiarity). Five hundred and two participants (113 male, average age 44.4 years, SD=14.0years) completed a series of questionnaires (Mindful Attention and Awareness Scale (MAAS), Cognitive Failures Questionnaire (CFQ) and Driver Behaviour Questionnaire (DBQ)), as well as study-specific questions about mind wandering during different personal states and across a range of road and traffic situations. All respondents reported mind wandering during driving at least some of the time. Mind wandering was more likely to be reported on familiar roads than on unfamiliar roads and when drivers are tired. Drivers who reported relatively more mind wandering were younger, reported less mindful attention in daily life, more cognitive failures, and more driving violations and lapses. Together, the findings suggest that mind wandering is common in everyday driving, however any link with crash risk remains unclear. Future research using self-report and naturalistic methods could provide more insight into relationships between mind wandering, error and crash risk. PMID- 27372441 TI - Rural casualty crashes on the Kings Highway: A new approach for road safety studies. AB - This paper will consider the contribution that changes in road geometry and driver visual information make to the incidence and distribution of road casualties in different driving environments. This relationship will be explored specifically for the Kings Highway, a major arterial road connecting Queanbeyan with coastal southern New South Wales, Australia. It introduces and suggests a new empirical approach of plotting crashes with road segmentation, calculating sinuosity indices and grades as key features of road geometry, and critical visual points as a behavioural component of road curvature, within a GIS context. It is an approach that might be used when detailed road geometry data is not available. The visualisation and segmentation approach in this research might be used for summarising crash rates and road geometry factors, and for comparing day/night and eastbound/westbound driving conditions. The results suggest some early interpretations for detailed road safety studies that might be considered at local or national levels. The rate of crashes increases according to changes in road geometry factors during the day and for eastbound travel. This is not the case for night driving where the incidence of crashes is similar on both straight and curved roads segments due to the headlight effect and limited background visual field. Crash clusters at day-time may be due to the stronger effect of road geometry (e.g. combination of curvature and vertical grade) on driver behaviour travelling eastbound. The outcomes suggest that it might be essential to consider the effect of environmental factors in any road safety and crash analysis studies. PMID- 27372442 TI - Mineral and metabolic profiles in tea leaves and flowers during flower development. AB - Tea [Camellia sinensis (L.) O. Kuntze] is one of the most popular non-alcoholic beverage crops in the world, and the physiological processes and gene regulations involved in development in tea plants have been well characterized. However, relatively little is known about the metabolic changes combined with mineral distributions that occur during flower development. Here we detected the contents of 11 elements in tea leaves and flowers and found that, some of them, especially phosphorus, sulfur and copper, showed significant changes during tea flowering. We also detected 122 metabolites in tea leaves and flowers and found that, 72 of them showed significant differences between flowers and leaves, of which sugars, organic acids, and flavonoids dominated. The sugars, such as trehalose and galactose, all accumulated in tea flowers, and the organic acids, such as malic acid, citric acid and fumaric acid involved in TCA cycle. The flavonoids, like epicatechin, catechin gallate and epigallocatechin, were more abundant in leaves. Furthermore, we found that the contents of 33 metabolites changed during the development of flowers. Especially, citric acid, phenylalanine and most flavonoids decreased while fructose and galactose increased during flowering stages in flowers. We also analyzed the correlations between the ions and metabolites and found that, some mineral nutrients including phosphorus, sulfur, manganese and zinc had close relations to organic acids, flavonoids, sugars and several amino acids during flowering. We mapped the metabolic pathway according to the KEGG database. This work will serve as the foundation for a systems biology approach to the understanding of mineral metabolism. PMID- 27372443 TI - Inverse modeling of the 137Cs source term of the Fukushima Dai-ichi Nuclear Power Plant accident constrained by a deposition map monitored by aircraft. AB - The amount of 137Cs released by the Fukushima Dai-ichi Nuclear Power Plant accident of 11 March 2011 was inversely estimated by integrating an atmospheric dispersion model, an a priori source term, and map of deposition recorded by aircraft. An a posteriori source term refined finer (hourly) variations comparing with the a priori term, and estimated 137Cs released 11 March to 2 April to be 8.12 PBq. Although time series of the a posteriori source term was generally similar to those of the a priori source term, notable modifications were found in the periods when the a posteriori source term was well-constrained by the observations. Spatial pattern of 137Cs deposition with the a posteriori source term showed better agreement with the 137Cs deposition monitored by aircraft. The a posteriori source term increased 137Cs deposition in the Naka-dori region (the central part of Fukushima Prefecture) by 32.9%, and considerably improved the underestimated a priori 137Cs deposition. Observed values of deposition measured at 16 stations and surface atmospheric concentrations collected on a filter tape of suspended particulate matter were used for validation of the a posteriori results. A great improvement was found in surface atmospheric concentration on 15 March; the a posteriori source term reduced root mean square error, normalized mean error, and normalized mean bias by 13.4, 22.3, and 92.0% for the hourly values, respectively. However, limited improvements were observed in some periods and areas due to the difficulty in simulating accurate wind fields and the lack of the observational constraints. PMID- 27372444 TI - A comparative study of terrestrial gamma dose rate in air measured by thermoluminescent dosimeter, portable survey meter and HPGe gamma spectrometer. AB - In this paper, three different widely-used measurement techniques for environmental gamma dose rate were studied and compared, i.e., the thermoluminescent dosimeter, the portable survey meter and the spectrometric analysis. Thirteen investigation sites were selected, and the TLDs were arranged to accumulate the radiation signals during an interval of about one quarter, the instant dose rates by using a portable survey meter were collected around the site, and top surface soils were sampled in the surroundings for radionuclides analyzing in laboratory. The results from these methods were compared, which revealed high correlations. The differences and possible uncertainties for the three methods were analyzed, inspired a further study should be conducted to have more successful estimation of dose rate in surface air. PMID- 27372445 TI - 'Not good enough:' Exploring self-criticism's role as a mediator between childhood emotional abuse & adult binge eating. AB - Empirical studies have identified emotional abuse in childhood (CEA) as a risk factor with long-term implications for psychological problems. Indeed, recent studies indicate it is more prevalent than behavioral forms of abuse, (i.e. childhood sexual and physical abuse) and the childhood trauma most clearly associated with subsequent eating pathology in adulthood. However, relatively little is understood about the mechanisms linking these distal experiences. This study explores three psychological mechanisms - self-criticism (SC), depression and anxiety symptoms - as plausible mediators that may account for the relationship between CEA and binge eating (BE) among adult women. Detailed telephone interviews conducted with a community-based sample of 498 adult women (mean age 44) assess BE, CEA and SC along with the most frequently researched psychological variables, anxiety and depression. Regression analyses reveal that BE is partially explained by CEA along with the three mediators. Bootstrapping analysis, which compares multiple mediators within a single model using thousands of repeated random sampling observations from the data set, reveals a striking finding: SC is the only psychological variable that makes a significant contribution to explaining BE severity. The unique role of punitive self evaluations vis-a-vis binge eating warrants additional research and, in the interim, that clinicians consider broadening treatment interventions accordingly. PMID- 27372446 TI - Changes in Hypertension Prevalence, Awareness, Treatment, and Control in High-, Middle-, and Low-Income Countries: An Update. AB - The aim of this paper was to critically evaluate recent publications on hypertension treatment and control in regions by income. Prevalence of hypertension is increasing worldwide, most prominently in low-income countries. Awareness, treatment, and control are most successful in North America while remaining a challenge in middle- and low-income countries. Easy access to medical care and aggressive use of pharmacotherapy are the key strategies which have proved to be successful in reducing the burden of hypertension on the population level. PMID- 27372448 TI - Estimating the effects of 17alpha-ethinylestradiol on stochastic population growth rate of fathead minnows: a population synthesis of empirically derived vital rates. AB - Urban freshwater streams in arid climates are wastewater effluent dominated ecosystems particularly impacted by bioactive chemicals including steroid estrogens that disrupt vertebrate reproduction. However, more understanding of the population and ecological consequences of exposure to wastewater effluent is needed. We used empirically derived vital rate estimates from a mesocosm study to develop a stochastic stage-structured population model and evaluated the effect of 17alpha-ethinylestradiol (EE2), the estrogen in human contraceptive pills, on fathead minnow Pimephales promelas stochastic population growth rate. Tested EE2 concentrations ranged from 3.2 to 10.9 ng L(-1) and produced stochastic population growth rates (lambda S ) below 1 at the lowest concentration, indicating potential for population decline. Declines in lambda S compared to controls were evident in treatments that were lethal to adult males despite statistically insignificant effects on egg production and juvenile recruitment. In fact, results indicated that lambda S was most sensitive to the survival of juveniles and female egg production. More broadly, our results document that population model results may differ even when empirically derived estimates of vital rates are similar among experimental treatments, and demonstrate how population models integrate and project the effects of stressors throughout the life cycle. Thus, stochastic population models can more effectively evaluate the ecological consequences of experimentally derived vital rates. PMID- 27372447 TI - Recent Updates on the Proximal Tubule Renin-Angiotensin System in Angiotensin II Dependent Hypertension. AB - It is well recognized that the renin-angiotensin system (RAS) exists not only as circulating, paracrine (cell to cell), but also intracrine (intracellular) system. In the kidney, however, it is difficult to dissect the respective contributions of circulating RAS versus intrarenal RAS to the physiological regulation of proximal tubular Na(+) reabsorption and hypertension. Here, we review recent studies to provide an update in this research field with a focus on the proximal tubular RAS in angiotensin II (ANG II)-induced hypertension. Careful analysis of available evidence supports the hypothesis that both local synthesis or formation and AT1 (AT1a) receptor- and/or megalin-mediated uptake of angiotensinogen (AGT), ANG I and ANG II contribute to high levels of ANG II in the proximal tubules of the kidney. Under physiological conditions, nearly all major components of the RAS including AGT, prorenin, renin, ANG I, and ANG II would be filtered by the glomerulus and taken up by the proximal tubules. In ANG II-dependent hypertension, the expression of AGT, prorenin, and (pro)renin receptors, and angiotensin-converting enzyme (ACE) is upregulated rather than downregulated in the kidney. Furthermore, hypertension damages the glomerular filtration barrier, which augments the filtration of circulating AGT, prorenin, renin, ANG I, and ANG II and their uptake in the proximal tubules. Together, increased local ANG II formation and augmented uptake of circulating ANG II in the proximal tubules, via activation of AT1 (AT1a) receptors and Na(+)/H(+) exchanger 3, may provide a powerful feedforward mechanism for promoting Na(+) retention and the development of ANG II-induced hypertension. PMID- 27372449 TI - Survival and long-term outcomes in late-onset Pompe disease following alglucosidase alfa treatment: a systematic review and meta-analysis. AB - A number of studies have assessed the efficacy of alglucosidase alfa as an enzyme replacement therapy (ERT) on motor and respiratory endpoints in patients with late-onset Pompe disease (LOPD). A previous review evaluated the clinical efficacy and safety of alglucosidase alfa; however, it is difficult to draw inferences from individual studies due to small patient populations, particularly in evaluating the benefit on survival. To evaluate the current evidence on the long-term efficacy of alglucosidase alfa with regard to survival, motor, and respiratory function in patients with LOPD in relation to the natural progression of the disease, a new systematic literature review was performed identifying studies that assessed either mortality, percent predicted forced vital capacity (% FVC), or the 6-min walk test (6MWT) among treated and untreated LOPD patients. Patient overlap was avoided by removing smaller studies or ensuring the use of only one conflicting study per outcome. Mortality was modeled using Poisson models for each treatment group. Outcomes were modeled using first- and second order fractional polynomial meta-analysis with fixed- and random-effects. Meta regression was used to explore sources of heterogeneity. Twenty-two publications pertaining to 19 studies/trials were selected, including 438 patients when accounting for overlaps, with the average study duration being 45.7 months. Patients treated with alglucosidase alfa in these studies had a nearly five-fold lower mortality rate than untreated patients (rate ratio: 0.21; 95 % credible interval: 0.11, 0.41). On average, % FVC declined consistently among untreated patients, including a 2.3 % decline after 12 months follow-up and 6.2 % decline after 48 months. This is in contrast to alglucosidase alfa-treated patients, who, on average, improved rapidly, with an increase of 1.4 % FVC after 2 months, followed by a slow regression back to baseline over a three-year period. Nonetheless, the relative difference between those treated and not grew over time, from 4.5 % FVC after 12 months to 6 % FVC after 48 months. In the 6MWT, alglucosidase alfa-treated patients on average had the largest improvement over the first 20 months of treatment of approximately 50 meters increase over baseline, with its substantial stabilization in the following years. By comparison, untreated patients do not show 6MWT improvement over time. Alglucosidase alfa has a beneficial effect in LOPD patients as demonstrated by improvements in survival and ambulation maintained over time, as well as prevention of deterioration in respiratory function. PMID- 27372451 TI - Age-period-cohort analysis of trends in amyotrophic lateral sclerosis incidence. AB - Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease with an unknown cause. Studies have reported that the incidence rate of ALS might be changing. As ALS is an age related disease, crude incidence could increase as population structure changes and overall life expectancy improves. Age-period cohort (APC) models are frequently used to investigate trends in demographic rates such as incidence. Age-specific incidence rate for ALS from 1996 to 2014 were taken from a population-based ALS register in Ireland. To circumvent the well-known identifiability issue in APC models, we apply the method of Partial Least Squares Regression to separate the effects of Age, Period and Cohort on ALS incidence over time. This APC analysis shows no cohort effect and the initial signs of a period effect; increasing incidence of ALS in the most recently diagnosed group. As further years of data accrue to the Irish register it will become clear if this effect emerges as a strong trend in the incidence of ALS in Ireland and replication of these analyses in other populations will show if our findings on temporal patterns in ALS incidence are shared elsewhere. PMID- 27372450 TI - Hearing and dementia. AB - Hearing deficits associated with cognitive impairment have attracted much recent interest, motivated by emerging evidence that impaired hearing is a risk factor for cognitive decline. However, dementia and hearing impairment present immense challenges in their own right, and their intersection in the auditory brain remains poorly understood and difficult to assess. Here, we outline a clinically oriented, symptom-based approach to the assessment of hearing in dementias, informed by recent progress in the clinical auditory neuroscience of these diseases. We consider the significance and interpretation of hearing loss and symptoms that point to a disorder of auditory cognition in patients with dementia. We identify key auditory characteristics of some important dementias and conclude with a bedside approach to assessing and managing auditory dysfunction in dementia. PMID- 27372452 TI - Gender-specific health implications of minority stress among lesbians and gay men. AB - OBJECTIVES: Lesbians and gay men are exposed to unique minority stressors. We examined the health implications of one type of distal minority stressor (victimisation) and one type of proximal minority stressor (sexual identity concealment due to anticipated stigma) among lesbians and gay men. Gender specific health implications were assessed. METHODS: Data were collected via an online survey involving an Australian sample of 1,470 gay men and 1,264 lesbians. Survey questions assessed demographics, experiences of different forms of sexual identity-related victimisation and sexual identity concealment in a variety of contexts. Health outcomes included self-reported general health, illicit drug use, frequency of alcohol consumption, smoking status, and weight status. RESULTS: Gay men reported higher rates of victimisation and identity concealment than lesbians. Controlling for demographic differences, experiences of victimisation were associated with poorer self-rated health, illicit drug use, and smoking among both gay men and lesbians. In contrast, identity concealment was linked with poorer health outcomes among lesbians only. CONCLUSIONS: Our findings offer new insights into the potential antecedents of the health inequalities that have previously been reported for these populations. PMID- 27372454 TI - Evidence for wild waterfowl origin of H7N3 influenza A virus detected in captive reared New Jersey pheasants. AB - In August 2014, a low-pathogenic H7N3 influenza A virus was isolated from pheasants at a New Jersey gamebird farm and hunting preserve. In this study, we use phylogenetic analyses and calculations of genetic similarity to gain inference into the genetic ancestry of this virus and to identify potential routes of transmission. Results of maximum-likelihood (ML) and maximum-clade credibility (MCC) phylogenetic analyses provide evidence that A/pheasant/New Jersey/26996-2/2014 (H7N3) had closely related H7 hemagglutinin (HA) and N3 neuraminidase (NA) gene segments as compared to influenza A viruses circulating among wild waterfowl in the central and eastern USA. The estimated time of the most recent common ancestry (TMRCA) between the pheasant virus and those most closely related from wild waterfowl was early 2013 for both the H7 HA and N3 NA gene segments. None of the viruses from waterfowl identified as being most closely related to A/pheasant/New Jersey/26996-2/2014 at the HA and NA gene segments in ML and MCC phylogenetic analyses shared >=99 % nucleotide sequence identity for internal gene segment sequences. This result indicates that specific viral strains identified in this study as being closely related to the HA and NA gene segments of A/pheasant/New Jersey/26996-2/2014 were not the direct predecessors of the etiological agent identified during the New Jersey outbreak. However, the recent common ancestry of the H7 and N3 gene segments of waterfowl origin viruses and the virus isolated from pheasants suggests that viral diversity maintained in wild waterfowl likely played an important role in the emergence of A/pheasant/New Jersey/26996-2/2014. PMID- 27372453 TI - Sugar addiction: the state of the science. AB - PURPOSE: As obesity rates continue to climb, the notion that overconsumption reflects an underlying 'food addiction' (FA) has become increasingly influential. An increasingly popular theory is that sugar acts as an addictive agent, eliciting neurobiological changes similar to those seen in drug addiction. In this paper, we review the evidence in support of sugar addiction. METHODS: We reviewed the literature on food and sugar addiction and considered the evidence suggesting the addictiveness of highly processed foods, particularly those with high sugar content. We then examined the addictive potential of sugar by contrasting evidence from the animal and human neuroscience literature on drug and sugar addiction. RESULTS: We find little evidence to support sugar addiction in humans, and findings from the animal literature suggest that addiction-like behaviours, such as bingeing, occur only in the context of intermittent access to sugar. These behaviours likely arise from intermittent access to sweet tasting or highly palatable foods, not the neurochemical effects of sugar. CONCLUSION: Given the lack of evidence supporting it, we argue against a premature incorporation of sugar addiction into the scientific literature and public policy recommendations. PMID- 27372455 TI - Leaching Behavior of Selected Trace and Toxic Metals in Coal Fly Ash Samples Collected from Two Thermal Power Plants, India. AB - Studies on leaching behavior of metals associated with coal fly ash (FA) are of great concern because of possible contamination of the aquatic environment. In the present study, leaching behavior of metals (As, Se, Cr, Pb, V, Zn, etc.) in two different FA samples (FA1 and FA2) was investigated at various pH (2-12), temperatures of leachate solution and using TCLP. At pH 2, the highest leaching was observed for Fe (21.6 and 32.8 ug/g), whereas at pH 12, Arsenic was found to have the highest leaching (1.5 and 2.4 ug/g) in FA1 and FA2. Leachate solution temperature showed a positive effect on the metal's leachability. In TCLP, most of the metal's leachability was observed to be higher than that of batch leaching tests. The present study suggests that, leaching of As and Se from FA samples can moderately affect ground/surface water quality at the study locations. PMID- 27372456 TI - Chloride Transport Parameters Prediction for a Clay-Loam Soil Column. AB - Water scarcity makes treated wastewater an unavoidable supplementary irrigation water source. Furthermore treated municipal wastewater quality depends on the fresh water quality and usage as well as on the wastewater treatment plant's degree and efficiency. The main recipient of all chemical compounds contained in this effluent, via irrigation, is soil. Models have been developed to predict factors involved in contaminants movement phenomenon through soil. In the reused effluent, chloride is much of a concern as a conservative pollutant. In this work the chloride breakthrough curves were determined for a clay-loam packed soil column by applying a one dimensional advection dispersion equation, to obtain estimates of the solute transport parameters. The comparisons between experimental and calculated results were satisfactory and also conclusions were derived about the flow conditions in the soil column and its uniformity. Also comparisons were made between calculated and cited in the literature values of the parameters satisfactorily. PMID- 27372457 TI - Kinetic Study of Nitrate Removal from Aqueous Solutions Using Copper-Coated Iron Nanoparticles. AB - Nitrates are considered hazard compounds for human health due to their tendency to be reduced to nitrites, in particular in reducing environment. Nano zero valent iron (nZVI) represents an efficient and low-cost adsorbent/reductive agent for nitrate removal from groundwater and wastewaters and a little addition of a second metal species (Cu, Pd, Ni, Ag) has proven to increase process effectiveness, by enhancing stability and oxidation resistance of nanoparticles. In this work Cu/Fe nanoparticles were loaded in a NO3- solution (100 mg L-1) and the removal efficiency was tested by monitoring nitrate concentration at selected time intervals. Results showed that the nitrate removal process involves both reduction and adsorption processes: the removal mechanism has been investigated, and the pseudo-first-order and pseudo-second-order-adsorption kinetic models were successfully tested. PMID- 27372459 TI - Publishers' note. PMID- 27372458 TI - Modified head shake sensory organization test: Sensitivity and specificity. AB - The Sensory Organization Test (SOT) of Computerized Dynamic Posturography (EquiTestTM equipment) is a valuable tool for investigating how an individual uses balance system sensory input (vestibular, vision, proprioception/somatosensory) to maintain quiet stance; however, it is limited as a screening tool for identifying peripheral vestibular system dysfunction. Previous research has shown that adding horizontal head-shake to portions of the standard SOT battery improved the identification of peripheral vestibular system asymmetry; however, flaws in the methods were noted. The objective of this work was to evaluate the sensitivity and specificity of the modified head-shake SOT (HS-SOT) protocol for identification of peripheral vestibular system lesion. Fifteen patients with chief complaint of instability, vertigo, and/or lightheadedness, with and without a caloric unilateral weakness (UW) and fifteen age-matched healthy controls were included in the final analysis. Ten of the 15 patients demonstrated a caloric UW>=25%. Participants completed standard conditions 2 and 5 of SOT with head still and during four horizontal head-shaking tasks (i.e., HS-SOT2-60 degrees /s, HS-SOT2-120 degrees /s, HS-SOT5-15 degrees /s, and HS-SOT5-60 degrees /s). Average equilibrium scores decreased as condition difficulty increased (SOT2, HS-SOT2-60 degrees /s, HS-SOT2-120 degrees /s, SOT 5, HS-SOT5-15 degrees /s, and HS-SOT5-60 degrees /s) for each group; as expected, a lower decline was noted for controls (slope=-6.59) compared to patients (slope= 11.69). The HS-SOT5-15 degrees /s condition was superior for identifying peripheral vestibular asymmetry (AUC=0.90 sensitivity=70%, specificity=100%), with the strongest correlation to caloric UW% (rs=-0.743, p=0.000006). HS-SOT5-15 degrees /s appears to be a promising screening measure for peripheral vestibular asymmetry. PMID- 27372460 TI - Arts, public health and the National Arts and Health Framework: a lexicon for health professionals. PMID- 27372461 TI - [The empowerment of the elderly patient in interaction with the geriatric physician]. AB - Previous studies have shown that there has been an increase in the empowerment of different groups of patients in their contact with physicians and nurses. However, no research to date has specifically focussed on the empowerment of elderly patients from the geriatrician's perspective . Research in this area is important in view of the rise in the ageing population, as elderly patients more frequently come into contact with physicians and more patient participation is required in care through processess such as 'shared decision making' and 'informed consent'. Through interviews with geriatricians from hospitals, this study attempted to gain insights into empowerment of elderly patients in consultations with geriatric physicians. Results show that there is a large degree of variation in empowerment among patients. The main factors that hinder or promote empowerment are the patients' cognitive state, their medical knowledge and educational level. Family and caregivers also appear to play a large role in the empowerment that elderly patients show in the physician's office. Three forms of active communication (asking questians, giving opinions, and expressing concerns) are the predominant manifestations of empowerment in elderly patients. Geriatricians unanimously agreed that empowerment influences the communication and relationship between the physician and the patient and also impacts decision making. Empowerment usually leads to greater therapy adherence and to more extensive patient examinations. PMID- 27372462 TI - Clinical benefit of midodrine hydrochloride in symptomatic orthostatic hypotension: a phase 4, double-blind, placebo-controlled, randomized, tilt-table study. AB - OBJECTIVE: Midodrine hydrochloride is a short-acting pressor agent that raises blood pressure in the upright position in patients with orthostatic hypotension. The US Food and Drug Administration's Subpart H approval, under which midodrine was initially approved, requires post-marketing studies to confirm midodrine's clinical benefit in this indication. The purpose of this study was to evaluate the clinical benefit of midodrine with regard to symptom response. METHODS: This was a double-blind, placebo-controlled, randomized, crossover, multicenter study (NCT01518946). Following screening, patients aged >=18 years with severe symptomatic orthostatic hypotension and on a stable dose of midodrine for at least 3 months were randomized to treatment with either their previous midodrine dose or placebo on day 1 and the respective alternate treatment on day 2. The primary endpoint measured time to syncopal symptoms or near-syncope using a 45 min tilt-table test at 1 h post-dose. RESULTS: Thirty-three patients were screened for inclusion: 19 received at least one dose of midodrine and had at least one post-dose measurement of the primary endpoint. The least-squares mean time to syncopal symptoms or near-syncope after tilt-table initiation (mean +/- standard error) was 1626.6 +/- 186.8 s for midodrine and 1105.6 +/- 186.8 s for placebo (difference, 521.0 s; 95 % confidence interval 124.2-971.7 s; p = 0.0131). There were 15 adverse events in 10 patients; all of these were mild or moderate in severity, with none considered by the investigators to be related to midodrine. INTERPRETATION: Midodrine is a well-tolerated and clinically effective treatment for symptomatic orthostatic hypotension. PMID- 27372463 TI - [Not Available]. PMID- 27372464 TI - [Not Available]. PMID- 27372465 TI - [Not Available]. PMID- 27372466 TI - [Not Available]. PMID- 27372467 TI - [Not Available]. PMID- 27372468 TI - Editor's Note. PMID- 27372469 TI - Moonshot Toward a Cure for Cancer. PMID- 27372470 TI - Unsuspected Herniated Lung Obstructing the Right Internal Jugular Vein and Internal Carotid Artery in a Patient with Thoracic Outlet Syndrome: MRI/MRA and MRV. PMID- 27372471 TI - Physicians' Perception of Sickle-cell Disease Pain. AB - The aim of this study was to evaluate the physician's perception of pain experienced by patients with sickle-cell disease (SCD). Pain experiences reported by patients were compared with physicians' perception of the patient's pain, and the treatment decision-making process was evaluated. Fifty-two patient-physician pairs were assessed. Before the clinic visit, the patients completed a 3-item on pain experienced 24 h prior to the visit and the PHQ-9. After the patient visit, the physicians completed a questionnaire assessing their perception of the patient's pain and a questionnaire on the factors taken into consideration when evaluating the patient's pain experience. The physicians rated the patients' pain as more intense than did the patients themselves; and there was agreement between pain intensity measurements (p < 0.05). The physicians' perception was influenced by the pain intensity reported by the patient, results of blood count at the time of the patient visit, and medication availability in the public health services. However, these factors were not predictive of the patient's pain intensity perceived by the physician. Patients' depressive symptoms were not predictive factor of the physicians' perception. Biochemical, genetic and symptomatic characteristics of SCD influenced the physicians' perception of the patient's pain experience, while psychosocial aspects did not. PMID- 27372472 TI - Disparities in Revascularization After ST Elevation Myocardial Infarction (STEMI) Before and After the 2002 IOM Report. AB - OBJECTIVES: To examine nationwide trends for racial disparities in Percutaneous Coronary Intervention after ST elevated Myocardial Infarction (STEMI). BACKGROUND: The Institute of Medicine (IOM) report published in 2002 showed that African Americans were less likely to receive coronary revascularization such as CABG and stents even after controlling for socioeconomics. It recommended increased awareness of these disparities among health professionals to reduce this. We hypothesized that increased awareness of disparities since this report would have translated to reduction in racial disparities in percutaneous coronary intervention. METHODS: A retrospective analysis was conducted using data from the Agency of Healthcare Research and Quality's (AHRQ) National Inpatient Sample (NIS) 1998-2007. All patients with STEMI during this period were identified. The proportion that received Percutaneous Coronary Intervention (PCI) during the incident admission was compared by different ethnicities over the time period. Multivariable regression for each year was conducted using Poisson regression with robust variances. The analysis controlled for gender, insurance status, co morbidities, hospital bed size, location and teaching status. RESULTS: Based on the database, about 2.04 million patients were managed for acute Myocardial Infarction from 1998 to 2007, of these 938,176 had STEMI. The primary PCI rate after STEMI among Caucasians was 29.1%, African Americans-23.3% and Hispanics 28.3% [P < 0.001] On multivariate regression, compared to Caucasians, African Americans and Hispanics respectively were 26% (IRR = 0.74) and 16% (IRR = 0.84) less likely to receive PCI (both with P < 0.001) during the entire study period. CONCLUSION: Ethnic disparities in primary PCI after STEMI persist despite the 2002 IOM report. PMID- 27372474 TI - Erratum to "Mortality in African-Americans Following Cardiac Resynchronization Therapy: A Single Center Experience" Journal of the National Medical Association 2016:108(1) February 30-39. PMID- 27372473 TI - Pleural Epithelioid Hemangioendothelioma: A Case Report and Literature Review. AB - Epithelioid hemangioendothelioma (EHE) is a rare neoplasm of vascular origin that can arise in multiple and varied tissue sites. Pleural epithelioid hemangioendothelioma (PEH), a subtype of EHE, is particularly less reported. Herein, we describe a case of PEH presented with left-sided back pain in a 68 year-old female, and her chest CT scan revealed thickening of the left pleura and left pleural effusion, the histological diagnosis was confirmed by both conventional examination and immunohistochemistry. A literature search utilizing PubMed, Embase, Ovid and Cochrane, Wanfang and Chinese National Knowledge infrastructure (CNKI) for PEH was conducted to investigate the characteristics of the disease, 26 related articles were retrieved and 40 cases of PEH were reported. According to available literature, the average age at presentation is 51.8 years and the disease occurred more often in men than women. The etiology of the disease remained unknown. Chest pain, cough, and dyspnea were the common symptoms. Computed tomography usually revealed pleural effusion and pleural thickening. Histological examinations revealed mainly epithelioid cells. Immunohistochemical stains were positive for vascular endothelial markers. PEH tends to have more aggressive behavior than tumors in other locations, thus effective treatment has not yet been established until now. Further studies are needed to analyze the prognostic factors, clinical features and treatment of PEH. PMID- 27372475 TI - The Health Care Institution, Population Health and Black Lives. AB - The ongoing existence of institutionalized racism and discriminatory practices in various systems (education, criminal justice, housing, employment) serve as root causes of poor health in Blacks Lives. Furthermore, these unjust social structures and their complex interplay result in inefficient utilization of health services and reactive or futile interactions with medical providers. Collectively, these factors contribute to racial disparities in health and treatment represents a significant portion of the nation's health care expenditures. In order for health care systems to optimize population health goals, racism must be recognized as a determinant of health. As anchor institutions in their respective communities, we offer hospitals and health systems a conceptual framework to address the issue within internal and external constructs. PMID- 27372477 TI - [Not Available]. PMID- 27372476 TI - Up-to date of glomerular disease. PMID- 27372478 TI - [Not Available]. PMID- 27372479 TI - [Not Available]. PMID- 27372480 TI - [Not Available]. PMID- 27372481 TI - [Not Available]. PMID- 27372482 TI - [Not Available]. PMID- 27372483 TI - [Not Available]. PMID- 27372484 TI - [Not Available]. PMID- 27372486 TI - [Not Available]. PMID- 27372485 TI - [Not Available]. PMID- 27372487 TI - [Not Available]. PMID- 27372488 TI - [Not Available]. PMID- 27372489 TI - [Not Available]. PMID- 27372490 TI - [Not Available]. PMID- 27372492 TI - [Not Available]. PMID- 27372491 TI - [Not Available]. PMID- 27372493 TI - [Not Available]. PMID- 27372495 TI - [Not Available]. PMID- 27372494 TI - [Not Available]. PMID- 27372496 TI - [Not Available]. PMID- 27372497 TI - [Not Available]. PMID- 27372499 TI - [Not Available]. PMID- 27372498 TI - [Not Available]. PMID- 27372500 TI - [Not Available]. PMID- 27372501 TI - [Not Available]. PMID- 27372502 TI - [Not Available]. PMID- 27372503 TI - [Not Available]. PMID- 27372504 TI - [Not Available]. PMID- 27372505 TI - [Not Available]. PMID- 27372506 TI - [Not Available]. PMID- 27372508 TI - Social stressors, coping behaviors, and depressive symptoms: A latent profile analysis of adolescents in military families. AB - We investigated the relationship between context-specific social stressors, coping behaviors, and depressive symptoms among adolescents in active duty military families across seven installations (three of which were in Europe) (N = 1036) using a person-centered approach and a stress process theoretical framework. Results of the exploratory latent profile analysis revealed four distinct coping profiles: Disengaged Copers, Troubled Copers, Humor-intensive Copers, and Active Copers. Multinomial logistic regressions found no relationship between military-related stressors (parental separation, frequent relocations, and parental rank) and profile membership. Analysis of variance results revealed significant and meaningful differences between the coping profiles and depressive symptomology, specifically somatic symptoms, depressive affect, positive affect, and interpersonal problems. Post-hoc analyses revealed that Active Copers, the largest profile, reported the fewest depressive symptoms. Accordingly, frequent use of diverse, active coping behaviors was associated with enhanced resilience. Discussion is provided regarding the promotion of adaptive coping behaviors within this developmental period and the context of military family life. PMID- 27372507 TI - Biodegradable Nanoparticles for Delivery of Therapeutics in CNS Infection. AB - Despite the significant advances in neurological medicine, it remains difficult to treat ailments directly involving the brain. The blood brain barrier (BBB) is a tightly regulated, selectively permeable barrier that restricts access from the blood into the brain extracellular fluid (BEF). Many conditions such as tumors or infections in the brain are difficult to treat due to the fact that drugs and other therapeutic agents are unable to easily pass through this relatively impermeable barrier. Human Immunodeficiency Virus (HIV) presents a particular problem as it is able to remain dormant in the brain for years protected from antiretroviral drugs by the BBB. The development of nanoscale carriers over the past few decades has made possible the delivery of therapies with the potential to overcome membrane barriers and provide specific, targeted delivery. This review seeks to provide a comprehensive overview of the various aspects of nanoparticle formulation and their applications in improving the delivery efficiency of drugs, specifically antiretroviral therapeutics to the brain to treat HIV. PMID- 27372509 TI - Interaction between Pin1 and its natural product inhibitor epigallocatechin-3 gallate by spectroscopy and molecular dynamics simulations. AB - The binding of epigallocatechin-3-gallate (EGCG) to wild type Pin1 in solution was studied by spectroscopic methods and molecular dynamics simulations in this research to explore the binding mode and inhibition mechanism. The binding constants and number of binding sites per Pin1 for EGCG were calculated through the Stern-Volmer equation. The values of binding free energy and thermodynamic parameters were calculated and indicated that hydrogen bonds, electrostatic interaction and Van der Waals interaction played the major role in the binding process. The alterations of Pin1 secondary structure in the presence of EGCG were confirmed by far-UV circular dichroism spectra. The binding model at atomic-level revealed that EGCG was bound to the Glu12, Lys13, Arg14, Met15 and Arg17 in WW domain. Furthermore, EGCG could also interact with Arg69, Asp112, Cys113 and Ser114 in PPIase domain. PMID- 27372510 TI - A study on the spectroscopic, energy band, and optoelectronic properties of alpha,omega-dihexylsexithiophene/tris(8-hydroxyquinolinate) gallium blends; DH6T/Gaq3 composite system. AB - In this work the optical response, spectroscopic behaviour, and optoelectronic properties of solution and solid state composite systems based on alpha,omega dihexylsexithiophene/tris(8-hydroxyquinolinate) gallium (DH6T/Gaq3) are studied upon the incorporation of different molar percentages of Gaq3. UV-vis, PL, FTIR spectrophotometers and SEM technique were utilized to perform the investigations. The results showed a reduced energy band (Eg) (from 2.33eV to 1.83eV) and a broadened absorption spectrum for the blend system when 29.8% molar of Gaq3 was incorporated. These were attributed to the enhanced intermolecular interactions that are brought about by the increased strength of pi-pi overlap between the molecular moieties. A mathematical formula was developed to interpret the non monotonic change occurred in Eg, while numerical calculations have been made to assign the type and nature of the electronic transitions governing the spectroscopic behaviour of the system. The results were elaborated and comprehensively discussed in terms of the exciton generation, energy band theory, molecular interactions, and spatial geometry. PMID- 27372511 TI - Spectroscopic studies of anthracyclines: Structural characterization and in vitro tracking. AB - A broad spectroscopic characterization, using ultraviolet-visible (UV-vis) and Fourier transform infrared absorption as well as Raman scattering, of two commonly used anthracyclines antibiotics (DOX) daunorubicin (DNR), their epimers (EDOX, EDNR) and ten selected analogs is presented. The paper serves as a comprehensive spectral library of UV-vis, IR and Raman spectra of anthracyclines in the solid state and in solution. The particular advantage of Raman spectroscopy for the measurement and analysis of individual antibiotics is demonstrated. Raman spectroscopy can be used to monitor the in vitro uptake and distribution of the drug in cells, using both 488nm and 785nm as source wavelengths, with submicrometer spatial resolution, although the cellular accumulation of the drug is different in each case. The high information content of Raman spectra allows studies of the drug-cell interactions, and so the method seems very suitable for monitoring drug uptake and mechanisms of interaction with cellular compartments at the subcellular level. PMID- 27372512 TI - Cysteamine capped CdS quantum dots as a fluorescence sensor for the determination of copper ion exploiting fluorescence enhancement and long-wave spectral shifts. AB - We described a turn-on fluorescence sensor for the determination of Cu(2+) ions, utilizing the quantum confinement effect of cadmium sulfide quantum dots capped with cysteamine (Cys-CdS QDs). The fluorescence intensity of the Cys-CdS QDs was both enhanced and red shifted (from blue-green to yellow) in the presence of Cu(2+). Fluorescence enhancement was linearly proportional to the concentration of Cu(2+) in the concentration range 2 to 10MUM. Other cations at the same concentration level did not significantly change the intensity and spectral maxima of Cys-CdS QDs, except Ag(+). The limit of detection was 1.5MUM. The sensor was applied to the determination of Cu(2+) in (spiked) real water samples and gave satisfactory results, with recoveries ranging from 96.7 to 108.2%, and with RSDs ranging from 0.3 to 2.6%. PMID- 27372513 TI - Micro-Raman spectroscopy in the identification of wulfenite and vanadinite in a Sasanian painted stucco fragment of the Ghaleh Guri in Ramavand, western Iran. AB - This paper reports the results of studies performed on a painted stucco fragment excavated at the Ghaleh Guri in Ramavand, western Iran, and dated back to the late Sasanian period (224-651AD). Analytical studies including micro-Raman spectroscopy (MU-Raman), micro-X-ray spectrometry (MU-XRF) and optical microscopy showed that red lead and vermilion were used as main pigments on this fragment. Moreover, carbon black was diagnosed to thinly cover some parts of the red lead. Peculiarly, wulfenite (PbMoO4) associated with vanadinite (Pb5(VO4)3Cl) was identified to compose a yellow stain sporadically dispersed on the other pigments. PMID- 27372514 TI - Specific transfer effects following variable priority dual-task training in older adults. AB - PURPOSE: Past divided attention training studies in older adults have suggested that variable priority training (VPT) tends to show larger improvement than fixed priority training (FPT). However, it remains unclear whether VPT leads to larger transfer effects. METHODS: In this study, eighty-three older adults aged between 55 and 65 received five 1-hour sessions of VPT, FPT or of an active placebo. VPT and FPT subjects trained on a complex dual-task condition with variable stimulus timings in order to promote more flexible and self-guided strategies with regard to attentional priority devoted to the concurrent tasks. Real-time individualized feedback was provided to encourage improvement. The active placebo group attended computer classes. Near and far modality transfer tasks were used to assess the generalization of transfer effects. RESULTS: Results showed that VPT induced significantly larger transfer effects than FPT on a near modality transfer task. Evidence for larger transfer effects in VPT than FPT on a far modality transfer task was also observed. Furthermore, the superiority of VPT on FPT in transfer effects was specific to the ability to coordinate two concurrent tasks. CONCLUSIONS: Results of this study help better understand the benefits of VPT attentional training on transfer effects, which is an essential outcome for cognitive training effectiveness and relevancy. PMID- 27372515 TI - Factors influencing the response to high-frequency repetitive transcranial magnetic stimulation in patients with subacute stroke. AB - BACKGROUND AND PURPOSE: High-frequency repetitive transcranial magnetic stimulation (rTMS) aids motor recovery in patients with subacute stroke. However, the response to high-frequency rTMS is highly variable between patients. The aim of this study was to identify the factors associated with improved motor function in response to high-frequency rTMS in subacute stroke patients with moderate to severe upper extremity motor involvement. METHODS: Sixty-two patients with subacute stroke were enrolled. rTMS was applied over the primary motor cortex of the affected hemisphere at 10 Hz with 1,000 pulses/day for 10 days. Upper limb motor function was scored with the upper limb of Fugl-Meyer Assessment (FMA-UL) score before intervention and immediately after intervention. All FMA-UL changes greater than or equal to 5 points were considered clinically significant. Potential influencing factors considered included patient characteristics, motor function, corticospinal tract (CST) integrity assessments, and genetics. Multivariate logistic regression analysis was used to identify the significance of each of these factors. RESULTS: We found that the two factors with the greatest impact on the improvement in FMA-UL score were: 1) the functional integrity of the CST, and 2) the brain-derived neurotrophic factor (BDNF) genotype (p < 0.05). Age tended to influence clinically significant changes in the FMA-UL score, although this effect was not significant. CONCLUSION: Our findings suggest that high-frequency rTMS interventions aimed at improving upper extremity motor function in patients with subacute stroke with moderate to severe motor involvement should be individually tailored according to functional CST status and BDNF genotype. PMID- 27372516 TI - [Main parasitic skin disorders]. AB - Cutaneous parasitic skin diseases are frequent in human pathology. There are few reliable epidemiological data on the prevalence and/or incidence of such diseases. Skin parasites are cosmopolitan but their global distribution is heterogenous; prevalence is especially high in subtropical and tropical countries. They are mainly due to arthropods (insects and mites). Many species of parasites are involved, explaining the diversity of their clinical signs. The most common are caused by ectoparasites such as scabies or pediculosis (head lice, body lice and pubic lice). Clinical signs may be related to the penetration of the parasite under the skin, its development, the inoculation of venom or allergic symptoms. Diagnosis can be easy when clinical signs are pathognomonic (e.g. burrows in the interdigital web spaces in scabies) or sometimes more difficult. Some epidemiological characteristics (diurnal or nocturnal bite, seasonality) and specific clinical presentation (single or multiple bites, linear or grouped lesions) can be a great diagnostic help. Modern non-invasive tools (dermoscopy or confocal microscopy) will play an important role in the future but the eye and experience of the specialist (dermatologist, parasitologist, infectious disease specialist or entomologist) remains for the time the best way to guide or establish a diagnosis. For most skin parasites, therapeutic proposals are rarely based on studies of high level of evidence or randomized trials but more on expert recommendations or personal experience. PMID- 27372517 TI - [Choice of initial regimen for antiretroviral-naive HIV patients: Analysis of motivation]. AB - OBJECTIVE: Several therapeutic combination antiretroviral therapy regimen are available for initial treatment in naive HIV infected patients. The choice of a particular regimen remains often subjective. The aim of this study was to determine factors associated with the choice of molecules in initial ARV prescriptions. METHODS: From 01/01 to 30/10/2014, every initial cART prescription was analyzed regarding patients and physicians characteristics. Then, prescriptions were evaluated by an independent committee of ART prescribers. RESULTS: One hundred and thirty two consecutive initial prescriptions by 34 physicians of 11 medical centers were included: 71 M, migrants: 57 %, MSM: 21 %, CD4<200/mm3: 26 %, HIV RNA>100 000 cp/mL (33 %). cART regimen were: NRTI/PI (43 %), NRTI/NNRTI (29.5 %), NRTI/integrase inhibitor (23 %). 75 % of initial cART regimen were consistent with expert guidelines recommendations. The choice of initial cART was not influenced by the type of HIV contamination risk group, patient's geographic origin, CD4 levels. In contrast, working or not (P=0.007), pregnancy wish (P=0.07), pregnancy (P=0.001), HIV RNA levels (P=0.02) and HIV primary infection (P=0.049) influenced the initial choice. Neither physician's age, nor physician's experience influenced this choice. The prescription's non accordance to 2013 French guidelines was mainly related to integrase inhibitor utilisation (P= 0.0001). CONCLUSION: Overall, cART initial choice is mostly consistent with guidelines. Primary HIV infection, procreation features and high viral load are the main factors influencing this choice. New regimen with better tolerability is prescribed even if it is not yet included in the guidelines. PMID- 27372518 TI - Corrigendum to "Global and gene-specific DNA methylation alterations in the adolescent amygdala and hippocampus in an animal model of caregiver maltreatment" [Behav. Brain Res. 298 (Pt A) (2016) 55-61]. PMID- 27372519 TI - MicroRNA-106a targets autophagy and enhances sensitivity of lung cancer cells to Src inhibitors. AB - OBJECTIVES: Src tyrosine kinase inhibitors (TKIs) significantly inhibit cell migration and invasion in lung cancer cell lines with minor cytotoxic effects. In clinical trials, however, they show modest activity in combination with chemotherapeutic agents. Possible resistance mechanisms include the induction of cytoprotective autophagy upon Src inhibition. Autophagy is a cellular recycling process that allows cell survival in response to a variety of stress stimuli including responses to various treatments. MATERIAL AND METHODS: We screened autophagic activity in A549, H460, and H1299 NSCLC cell lines treated with two different Src-TKIs (saracatinib, dasatinib) or shRNA targeting SRC. The autophagy response was determined by LC3B-I to -II conversion, increased ULK1 epxression and increased GFP-LC3B dot formation. Autophagy was inhibited by pharmacological (bafilomycin A, chloroquine) or genetic (ULK1 shRNA) means. Expression of miR 106a and miR-20b was analyzed by qPCR, and we used different lentivral vectors for ectopic expression of either miR-106a mimetics, anti-sense miR-106a or different miR-106a-363 cluster constructs. RESULTS: In the current study we found that Src-TKIs induce autophagy in lung adenocarcinoma cell lines and that a combination of autophagy and Src tyrosine kinase inhibition results in cell death. Moreover, Src-TKI induced autophagy depends on the induction of the key autophagy kinase ULK1. This ULK1 upregulation is caused by downregulation of the ULK1-targeting microRNA-106a. An inverse correlation of miR-106a and ULK1 expression was seen in lung adenocarcinoma. Accordingly, ectopic expression of miR-106a in combination with Src-TKI treatment resulted in significant cell death as compared to control transduced cells. CONCLUSIONS: Autophagy protects lung adenocarcinoma cells from Src-TKIs via a newly identified miR-106a-ULK1 signaling pathway. The combined inhibition of Src and ULK1/autophagy might represent a promising treatment option for future clinical trials. Lastly, our data might challenge the term "oncogenic" miR-106a as it can promote sensitivity to Src-TKIs thereby underlining the context-dependent function of miRNAs. PMID- 27372520 TI - USP7 inhibitors, downregulating CCDC6, sensitize lung neuroendocrine cancer cells to PARP-inhibitor drugs. AB - OBJECTIVES: CCDC6 gene product is a tumor-suppressor pro-apoptotic protein, substrate of ATM, involved in DNA damage response and repair. Altered levels of CCDC6 expression are dependent on post-translational modifications, being the de ubiquitinating enzyme USP7 responsible of the fine tuning of the CCDC6 stability. Thus, our aim was to investigate CCDC6 and USP7 expression levels in Lung Neuroendocrine Tumors (L-NETs) to verify if they correlate and may be exploited as novel predictive therapeutic markers. MATERIALS AND METHODS: Tumor tissues from 29 L-NET patients were investigated on tissue microarrays. CCDC6 levels were scored and correlated with immunoreactivity for USP7. Next generation sequencing (NGS) of a homogenous group of Large Cell Neuroendocrine Carcinoma (LCNEC) (N=8) was performed by Ion AmpliSeq NGS platform and the Ion AmpliSeq Cancer Hotspot Panel v2. The inhibition of USP7, using P5091, was assayed in vitro to accelerate CCDC6 turnover in order to sensitize the neuroendocrine cancer cells to PARP inhibitors, alone or in association with cisplatinum. RESULTS: The immunostaining of 29 primary L-NETs showed that the intensity of CCDC6 staining correlated with the levels of USP7 expression (p<=0.05). The NGS analysis of 8 LCNEC revealed mutations in the hot spot regions of the p53 gene (in 6 out of 8). Moreover, gene polymorphisms were identified in the druggable STK11, MET and ALK genes. High intensity of p53 immunostaining was reported in the 6 tissues carrying the TP53 mutations. The inhibition of USP7 by P5091 accelerated the degradation of CCDC6 versus control in cycloheximide treated L-NET cells in vitro and sensitized the cells to PARP-inhibitors alone and in combination with cisplatinum. CONCLUSION: Our data suggest that CCDC6 and USP7 have a predictive value for the clinical usage of USP7 inhibitors in combination with the PARP-inhibitors in L-NET in addition to standard therapy. PMID- 27372521 TI - Prophylactic mesh can be used safely in the prevention of incisional hernia after bilateral subcostal laparotomies. AB - BACKGROUND: The use of prophylactic mesh to prevent incisional hernia is becoming increasingly common in midline laparotomies and colostomies. The incidence of incisional hernia after subcostal laparotomies is lower than after midline incisions. Nevertheless, the treatment of subcostal incisional hernia is considered to be more complex. Currently, there are no published data about mesh augmentation procedures to close these laparotomies. METHODS: This was a longitudinal, prospective, cohort study of patients undergoing a bilateral subcostal laparotomy in elective operations. The mesh group was a group of patients operated consecutively between 2011 and 2013 with a prophylactic self fixation mesh. The control group was selected from a retrospective analysis of patients operated between 2009 and 2010 and closed with a conventional protocol of 2-layer closure. The incidence of incisional hernia was recorded both clinically and radiologically for 2 years. RESULTS: A total of 57 patients were included in the control group and 58 in the mesh group. Most patients underwent gastric, hepatic, and pancreatic operations. Both groups were homogeneous in terms of their clinical and demographic characteristics. Operative time and hospital stay were similar in both groups. Both groups had a comparable rate of local and systemic complications. Ten patients (17.5%) in the control group developed an incisional hernia, and only 1 patient (1.7%) in the mesh group developed an incisional hernia (P = .0006). CONCLUSION: The incidence of incisional hernia after a conventional closure of bilateral subcostal laparotomy is significant. The use of a mesh augmentation procedure for closing bilateral subcostal laparotomies is safe and may reduce the incidence of incisional hernia. PMID- 27372522 TI - Congenital diaphragmatic hernia manifesting after an altitude flight. PMID- 27372523 TI - Treatment recommendations by clinicians in stage I non-small cell lung cancer: A study of factors that influence the likelihood of accounting for the patient's preference. AB - OBJECTIVES: Surgery and stereotactic ablative radiotherapy (SABR) are both curative treatment options for patients with stage I non-small cell lung cancer (NSCLC). Shared decision making (SDM) has been advocated in this patient group. This study explored clinician decision making in relation to the stated treatment preferences of patients. METHODS: In a previous study, we conducted a binary choice experiment with hypothetical cases among 126 clinicians. Secondary data analysis was performed using multilevel logistic regression models, in which random differences between clinicians' decisions were taken into account. We analyzed the influence of patient- and clinician-related characteristics, and uncertainty as experienced by clinicians about their recommendation on the clinician's decision (either in line with the patient's preference or not). RESULTS: Significant interactions were observed between patient- and clinician related characteristics, indicating that patient preferences were selectively taken into account, depending on clinicians' specialty, their views about the comparability of cancer-related outcomes following surgery and SABR, and the degree of uncertainty about the treatment recommendation. CONCLUSIONS: Our findings suggest that SDM for stage I NSCLC care is largely influenced by how clinicians weigh available scientific evidence. PRACTICE IMPLICATIONS: Clinicians should involve lung cancer patients more and ask for their preferences in making treatment recommendations. PMID- 27372524 TI - An e-health intervention to support the transition of young people with long-term illnesses to adult healthcare services: Design and early use. AB - OBJECTIVE: Co-design information and website to support adolescents and young adults with long-term illnesses in their transition to adult healthcare. METHODS: A participatory iterative process involving a survey (n=207), twenty-one interviews, six participatory workshops, six video recordings, two advisory groups, and a co-design group to identify needs and preferences for e-health and information provision, was used to develop an appropriate intervention. RESULTS: Adolescents and young people expressed preferences for information that was trustworthy, empowering, colorful, easily downloaded online and written using non patronizing language. They desired video testimonials of experiences from young adults who had transitioned to adult healthcare and wanted advice about becoming more independent, managing their condition, preparing for the transition, and information about medications and the differences between child and adult healthcare. They also wanted information about the location and configuration of adult healthcare, key hospital personnel, and frequently asked questions. CONCLUSION: The participatory iterative process led to the development of an online resource specifically tailored to the adolescents and young people's transition needs and information preferences. Preliminary feedback indicates that it is a valued resource. PRACTICE IMPLICATIONS: The www.SteppingUP.ie website has the potential to help prepare its target population group for the transition to adult healthcare. PMID- 27372525 TI - Nurse-led patient-centered self-management support improves HbA1c in patients with type 2 diabetes-A randomized study. AB - OBJECTIVES: The aim of this study was to evaluate the effect of a patient centered self-management support, in type 2 diabetes (T2D) with regard to metabolic changes. METHODS: 182 patients were randomized into group intervention (GI), individual intervention (II) or internal controls (IC). An external control (EC) group was recruited from another county council. The intervention consisted of six sessions that featured themes, which regarded different views of their illness experiences. Data were collected in 2010 and 2011. RESULTS: HbA1c was significantly decreased at 12-month follow-up with 5mmol/mol in the GI and 4mmol/mol in the II. In the IC group, the HbA1c was close to baseline. The EC group had increased HbA1c, though not significantly. When the HbA1c difference at baseline was adjusted, there was a significant difference between intervention groups and the EC-group. CONCLUSION: Patient-centered self-management support, led by nurses, can lower HbA1c among patients with type 2 diabetes. PRACTICE IMPLICATIONS: It is possible to train diabetes specialist nurses in clinical patient-centered care, and simultaneously influence patients' metabolic balance positively. PMID- 27372526 TI - Worldwide Hypertension: The Growing Threat and the Potential Opportunities. PMID- 27372527 TI - Hypertension and Related Cardiovascular Disease Burden in China. AB - BACKGROUND: With rapid economic development, urbanization, and an aging population, cardiovascular diseases (CVDs) have become the leading cause of death in China. OBJECTIVES: The aim of this study was to provide a comprehensive review on the prevalence, awareness, treatment, and control of hypertension (HTN) as well as blood pressure (BP)-related morbidity and mortality of CVD in Chinese adults over time. FINDINGS: The prevalence of HTN in China is high and increasing. Recent estimates are variable but indicate 33.6% (35.3% in men and 32% in women) or 335.8 million (178.6 million men and 157.2 million women) of the Chinese adult population had HTN in 2010, which represents a significant increase from previous surveys. BP-related CVD remains the leading cause of death in Chinese adults, with stroke being the predominant cause of cardiovascular deaths. Of those with HTN, 33.4% (30.4% in men and 36.7% in women) were aware of their condition, 23.9% (20.6% in men and 27.7% in women) were treated, and only 3.9% (3.5% in men and 4.3% in women) were controlled to the currently recommended target of BP <140/90 mm Hg. Awareness and treatment of HTN have improved over time, but HTN control has not. Geographic differences in the prevalence, awareness, treatment, and control of HTN are evident, both in terms of a north south gradient and urban-rural disparity. CONCLUSIONS: The prevalence of HTN is high and increasing, while the control rate is low in Chinese adults. Combatting HTN and BP-related morbidity and mortality will require a comprehensive approach at national and local levels. The major challenge moving forward is to develop and implement effective, practical, and sustainable prevention and treatment strategies in China. PMID- 27372528 TI - Sodium Intake, Blood Pressure, and Dietary Sources of Sodium in an Adult South Indian Population. AB - BACKGROUND: The association between prevalence of hypertension and its relationship with dietary sodium intake has never been published from large epidemiological studies in the South Indian population before. OBJECTIVES: To assess sodium intake and its association with blood pressure, and major dietary sources of sodium in an adult population in southeastern India. METHODS: This study included a representative population-based sample of 8080 individuals (57% women) >20 years of age. Individuals with previous history of hypertension and outliers for sodium intake were excluded, resulting in a sample size of 6876, with 4269 from semi-urban/urban and 2607 from rural areas. Baseline measurements included evaluation of systolic (SBP) and diastolic (DBP) blood pressures, anthropometric, sociodemographic, and psychosocial parameters. Based on 24-hour recall, we calculated total daily sodium intake and the percentage contributed by each food group to the total sodium intake. Participants were assigned based on quintiles of dietary sodium intake. Mixed-effects multivariable linear regression models assessed the association of SBP and DBP with sodium intake. FINDINGS: Men had higher mean sodium intake (4.1 +/- 2 versus 3.2 +/- 1.7 g/day; P < 0.01) with higher mean SBP and DBP (123/77 versus 117/74 mm Hg; P < 0.01), and higher prevalence of hypertension (22.2% versus 12.9%; P < 0.01) compared with women. Mean dietary sodium intake was significantly higher in the hypertensive men (4.2 +/- 2 g/day) and women (3.2 +/- 1.7 g/day) compared with normotensive men (4 +/- 2 g/day), and women (3.2 +/- 1.7 g/day; P < 0.05). Significant (P < 0.01) increases in SBP and DBP were evident in men, but not women with increasing quintile of sodium intake. After multivariable adjustments, sodium intake was independently associated with SBP, but not DBP, in both sexes. The predominant source of dietary sodium in both semi-urban/urban and rural populations was from homemade foods where salt is part of the traditional recipe. CONCLUSION: In a South Indian population, the dietary intake of sodium was higher than recommendations by major dietary guidelines and was an independent predictor of SBP. PMID- 27372529 TI - Expanding the Role of Nurses to Improve Hypertension Care and Control Globally. AB - The role of the nurse in improving hypertension control has expanded over the past 50 years, complementing and supplementing that of the physician. Nurses' involvement began with measuring and monitoring blood pressure (BP) and patient education and has expanded to become one of the most effective strategies to improve BP control. Today the roles of nurses and nurse practitioners (NPs) in hypertension management involve all aspects of care, including (1) detection, referral, and follow up; (2) diagnostics and medication management; (3) patient education, counseling, and skill building; (4) coordination of care; (5) clinic or office management; (6) population health management; and (7) performance measurement and quality improvement. The patient-centered, multidisciplinary team is a key feature of effective care models that have been found to improve care processes and control rates. In addition to their clinical roles, nurses lead clinic and community-based research to improve the hypertension quality gap and ethnic disparities by holistically examining social, cultural, economic, and behavioral determinants of hypertension outcomes and designing culturally sensitive interventions to address these determinants. PMID- 27372530 TI - Research and Development of Information and Communication Technology-based Home Blood Pressure Monitoring from Morning to Nocturnal Hypertension. AB - Asians have specific characteristics of hypertension (HTN) and its relationship with cardiovascular disease. The morning surge in blood pressure (BP) in Asians is more extended, and the association slope between higher BP and the risk for cardiovascular events is steeper in this population than in whites. Thus, 24-hour BP control including at night and in the morning is especially important for Asian patients with HTN. There are 3 components of "perfect 24-hour BP control": the 24-hour BP level, adequate dipping of nocturnal BP (dipper type), and adequate BP variability such as the morning BP surge. The morning BP-guided approach using home BP monitoring (HBPM) is the first step toward perfect 24-hour BP control. After controlling morning HTN, nocturnal HTN is the second target. We have been developing HBPM that can measure nocturnal BP. First, we developed a semiautomatic HBPM device with the function of automatic fixed-interval BP measurement during sleep. In the J-HOP (Japan Morning Surge Home Blood Pressure) study, the largest nationwide home BP cohort, we successfully measured nocturnal home BP using this device with data memory, 3 times during sleep (2, 3, and 4 am), and found that nocturnal home BP is significantly correlated with organ damage independently of office and morning BP values. The second advance was the development of trigger nocturnal BP (TNP) monitoring with an added trigger function that initiates BP measurements when oxygen desaturation falls below a variable threshold continuously monitored by pulse oximetry. TNP can detect the specific nocturnal BP surges triggered by hypoxic episodes in patients with sleep apnea syndrome. We also added the lowest heart rate-trigger function to TNP to detect the "basal nocturnal BP," which is determined by the circulating volume and structural cardiovascular system without any increase in sympathetic tonus. This double TNP is a novel concept for evaluating the pathogenic pressor mechanism of nocturnal BP. These data are now collected using an information and communication technology (ICT)-based monitoring system. The BP variability includes different time-phase variability from the shortest beat-by-beat, positional, diurnal, day-by-day, visit-to-visit, seasonal, and the longest yearly changes. The synergistic resonance of each type of BP variability would produce great dynamic BP surges, which trigger cardiovascular events. Thus, in the future, the management of HTN based on the simultaneous assessment of the resonance of all of the BP variability phenotypes using a wearable "surge" BP monitoring device with an ICT-based data analysis system will contribute to the ultimate individualized medication for cardiovascular disease. PMID- 27372532 TI - Hypertension in Canada: Past, Present, and Future. AB - Canada has an extremely successful hypertension detection and treatment program. The aim of this review was to highlight the historic and current infrastructure and initiatives that have led to this success, and the outlook moving forward into the future. We discuss the evolution of hypertension awareness and control in Canada; contributions made by organizations such as the Canadian Hypertension Society, Blood Pressure Canada, and the Canadian Hypertension Education Program; the amalgamation of these organizations into Hypertension Canada; and the impact that Hypertension Canada has had on hypertension care in Canada. The important contribution that public policy and advocacy can have on prevention and control of blood pressure in Canada is described. We also highlight the importance of population-based strategies, health care access and organization, and accurate blood pressure measurement (including ambulatory, home, and automated office modalities) in optimizing hypertension prevention and management. We end by discussing how Hypertension Canada will move forward in the near and longer term to address the unmet residual risk attributable to hypertension and associated cardiovascular risk factors. Hypertension Canada will continue to strive to enhance hypertension prevention and control rates, thereby improving the quality of life and cardiovascular outcomes of Canadians, while at the same time creating a hypertension care model that can be emulated across the world. PMID- 27372531 TI - Modern Management and Diagnosis of Hypertension in the United Kingdom: Home Care and Self-care. AB - BACKGROUND: The effective diagnosis and management of hypertension is one of the most important parts of cardiovascular prevention internationally and this is no different in the United Kingdom. Approximately 14% of the UK population currently receive treatment for hypertension. Recent UK guidelines from the National Institute of Health and Care Excellence have placed greater emphasis on the utilization of out-of-office measurement of blood pressure to more accurately diagnose hypertension. OBJECTIVE: The aim of the present study was to provide a state-of-the-art review of the evidence for screening, diagnosing, and managing hypertension, as implemented in the United Kingdom, with an emphasis on the role of self-monitored and ambulatory blood pressure monitoring in routine clinical care. METHOD: Consideration was given to the use of ambulatory and home monitoring to confirm a diagnosis of hypertension and the use of self-monitoring and self-management to monitor and guide treatment. The evidence for the use of self-monitoring in patients with hypertension was examined, both in isolation, and in combination with lifestyle and treatment interventions. FINDINGS: There is a place for self-monitored blood pressure in specific underresearched populations such as the elderly, specialist conditions, ethnic groups, and during pregnancy and this is discussed here. CONCLUSIONS: The evidence supporting the use of out of-office monitoring in all aspects of routine clinical care has increased substantially in recent years and is reflected in increased utilization by patients and clinicians alike. Several areas require further research but it is clear that out-of-office monitoring is here to stay and is fast becoming an important part of hypertension management in the United Kingdom. PMID- 27372533 TI - Heart Disease in Syrian Refugee Children: Experience at Jordan University Hospital. AB - BACKGROUND: Since March 2011, an estimated 600,000 Syrian refugees crossed into Jordan, of which 52% were children. Demand for health care is overwhelming. The burden of heart disease in Syrian refugee children is not known. The aim of this study WAS to describe heart disease in Syrian refugee children in terms of diagnoses, presentation, outcome, and funding sources for treatment. METHODS: From April 1, 2012 to April 30, 2014, data on Syrian refugee children who were referred to the Pediatric Cardiology Department at Jordan University Hospital and were found to have heart disease was recorded. In this study, we describe diagnoses, presentations, complications, and mortality. We discuss therapeutic procedures and their funding sources. Patients were followed until July 31, 2014. FINDINGS: In all, 119 children, median age 2 years (6 days to 16 years), were diagnosed with heart disease. At presentation, 37% had failure to thrive, 13% had severe complications, and 32% of cyanotic patients had severe hypoxia with oxygen saturation of <70%. Mortality rate was 14% by end of follow up. Of 73 surgical procedures recommended, only 28 were funded and performed; others have been waiting for a median of 223 days (35-534 days). Funding for procedures came from multiple sources; including the United Nations, governmental and nongovernmental organizations, and individual donations. CONCLUSION: Heart disease in Syrian refugee children constitutes a major problem for both patients and health systems of host countries. Late presentation and diagnosis, high rate of complications, suboptimal living conditions, lack of funding, shortage of specialized centers and personnel, and high mortality rates are among the major challenges facing this patient population. PMID- 27372534 TI - Trends in Coronary Heart Disease Epidemiology in India. AB - Cardiovascular diseases, especially coronary heart disease (CHD), are epidemic in India. The Registrar General of India reported that CHD led to 17% of total deaths and 26% of adult deaths in 2001-2003, which increased to 23% of total and 32% of adult deaths in 2010-2013. The World Health Organization (WHO) and Global Burden of Disease Study also have highlighted increasing trends in years of life lost (YLLs) and disability-adjusted life years (DALYs) from CHD in India. In India, studies have reported increasing CHD prevalence over the last 60 years, from 1% to 9%-10% in urban populations and <1% to 4%-6% in rural populations. Using more stringent criteria (clinical +/- Q waves), the prevalence varies from 1%-2% in rural populations and 2%-4% in urban populations. This may be a more realistic prevalence of CHD in India. Case-control studies have reported that important risk factors for CHD in India are dyslipidemias, smoking, diabetes, hypertension, abdominal obesity, psychosocial stress, unhealthy diet, and physical inactivity. Suitable preventive strategies are required to combat this epidemic. PMID- 27372535 TI - Efficient regioselective acylation of quercetin using Rhizopus oryzae lipase and its potential as antioxidant. AB - The present investigation describes the regioselective enzymatic acylation of quercetin with ferulic acid using Rhizopus oryzae lipase. Optimization of reaction parameters resulted in 93.2% yield of the ester synthesized using 750IU of lipase in cyclo-octane at a temperature of 45 degrees C. The reaction was successfully carried out upto 25g scale. The ester synthesized was analyzed by (1)H Nuclear magnetic resonance spectroscopy. The ester synthesized (quercetin ferulate) showed higher antiradical activity as compared to ascorbic acid using the 2,2-diphenyl-1-picrylhydrazyl radical method. These results on enzyme catalyzed acylation of quercetin might be used to prepare and scale-up other flavonoids derivatives. PMID- 27372536 TI - A Computer-Aided Detection System for Digital Chest Radiographs. AB - Computer-aided detection systems aim at the automatic detection of diseases using different medical imaging modalities. In this paper, a novel approach to detecting normality/pathology in digital chest radiographs is proposed. The problem tackled is complicated since it is not focused on particular diseases but anything that differs from what is considered as normality. First, the areas of interest of the chest are found using template matching on the images. Then, a texture descriptor called local binary patterns (LBP) is computed for those areas. After that, LBP histograms are applied in a classifier algorithm, which produces the final normality/pathology decision. Our experimental results show the feasibility of the proposal, with success rates above 87% in the best cases. Moreover, our technique is able to locate the possible areas of pathology in nonnormal radiographs. Strengths and limitations of the proposed approach are described in the Conclusions. PMID- 27372537 TI - Interobserver variance in diagnostic arthroscopy of the knee : "Wie objektiv sind arthroskopische Befunde wirklich?". AB - We assessed the interindividual diagnostic variance of 39 experienced arthroscopists by the Kappa Cohen interobserver variation analysis using videotapes of eight different patients with different diagnoses. Arthroscopically normal findings showed a relatively acceptable interobserver correlation. Pathological changes, in contrast, often showed very little correlation, especially in the synovial membrane of the suprapatellar recess, in the cartilage of the femoropatellar groove and the posterior cruciate ligament. In patellar alignment there was also great interobserver variation. CLINICAL RELEVANCE: When comparing arthroscopic findings with other imaging techniques the above results should be taken into account. Furthermore, these results will affect the significance of medical expertise based only on pictures. In addition, medical cost billing, which is based on arthroscopic findings, has to take into account that a wrong diagnosis is possible and therefore charges will be wrong. PMID- 27372538 TI - [Not Available]. PMID- 27372539 TI - Recent Advances in Sarcopenia Research in Asia: 2016 Update From the Asian Working Group for Sarcopenia. AB - Sarcopenia was recently classified a geriatric syndrome and is a major challenge to healthy aging. Affected patients tend to have worse clinical outcomes and higher mortality than those without sarcopenia. Although there is general agreement on the principal diagnostic characteristics, initial thresholds for muscle mass, strength, and physical performance were based on data from populations of predominantly Europid ancestry and may not apply worldwide. The Asian Working Group for Sarcopenia (AWGS) issued regional consensus guidelines in 2014, and many more research studies from Asia have since been published; this review summarizes recent progress. The prevalence of sarcopenia estimated by the AWGS criteria ranges between 4.1% and 11.5% of the general older population; however, prevalence rates were higher in Asian studies that used European Working Group on Sarcopenia in Older People cut-offs. Risk factors include age, sex, heart disease, hyperlipidemia, daily alcohol consumption, and low protein or vitamin intake; physical activity is protective. Adjusting skeletal muscle mass by weight rather than height is better in showing the effect of older age in sarcopenia and identifying sarcopenic obesity; however, some Asian studies found no significant skeletal muscle loss, and muscle strength might be a better indicator. Although AWGS 2014 diagnostic cut-offs were generally well accepted, some may require further revision in light of conflicting evidence from some studies. The importance of sarcopenia in diverse therapeutic areas is increasingly evident, with strong research interest in sarcopenic obesity and the setting of malignancy. Pharmacologic interventions have been unsatisfactory, and the core management strategies remain physical exercise and nutritional supplementation; however, further research is required to determine the most beneficial approaches. PMID- 27372540 TI - Spontaneous Bilateral Chylothorax Caused by a Sneeze: An Unusual Entity with Good Prognosis. PMID- 27372541 TI - Diffuse Idiopathic Neuroendocrine Cell Hyperplasia, Tumorlets and Typical Carcinoid Tumors. PMID- 27372542 TI - Efficacy of Double Bronchodilation (LABA+LAMA) in Patients with Chronic Obstructive Pulmonary Disease (COPD) and Lung Cancer. PMID- 27372543 TI - Embedding continuous quality improvement processes in multidisciplinary teams in cancer care: exploring the boundaries between quality and implementation science. AB - Objective The aim of the present study was to identify key enabling factors for engaging multidisciplinary teams (MDTs) in cancer care across the spectrum of translational research and quality improvement (QI) projects. Methods The study was conducted in two large Sydney metropolitan hospitals. Qualitative methods, including structured observations of MDT meetings and semi-structured interviews with MDT leaders and champions, were used to identify how teams interact with and generate research and implementation initiatives. Enabling factors for and barriers to the engagement of MDTs in translational research and QI were identified. Results Four key enabling factors emerged from the analysis of data generated from observing 43 MDT meetings and 18 semi-structured interviews: (1) access to high-quality data around individual and team performance; (2) research active team leaders; (3) having experts, such as implementation scientists, embedded into teams; and (4) having dedicated research or QI-focused meetings. Barriers included a lack of time, administrative support, research expertise and access to real-time data. Conclusions The identification of enabling factors for and barriers to translational research and QI provides evidence for how multidisciplinary cancer care teams may best be engaged in research and QI that aims to improve service and care outcomes. What is known about the topic? MDTs are key to the delivery of cancer care in Australia, but there is scant research into how teams can best be engaged in translating research from basic science through to implementation science and QI. What does this paper add? This paper provides new evidence from an immersive study of cancer care MDTs in two large metropolitan hospitals in Sydney (NSW, Australia), regarding the key enabling factors for and barriers to successful engagement in translational research and QI in cancer care. What are the implications for practitioners? Cancer care professionals in MDTs are presented with an opportunity to embed translational research and QI into cancer care. MDTs can operate as an ideal vehicle to look beyond individual patient outcomes to broader trends and population health outcomes. PMID- 27372544 TI - Lichen Nitidus Arising on Vitiligo: A New Variant of the Isotopic Coresponse. PMID- 27372545 TI - Systemic Absorption of Topical Tacrolimus in Metastatic Crohn Disease With Skin Ulcers. PMID- 27372546 TI - Gene-environment interactions in a rat model of depression. Maternal separation affects neurotensin in selected brain regions. AB - Although the etiology of major psychiatric disorders has not been elucidated, accumulating evidence indicates that both genetic and early environmental factors play a role. We have previously demonstrated behavioral and neurochemical changes both in non-manipulated genetic rat models of depression, such as Flinders Sensitive Line (FSL) and Fawn Hooded (FH), and in normal rats following maternal separation (MS). The aim of the present study was to extend this work by exploring whether neurotensin (NT), a peptide implicated in several psychiatric disorders, is altered in a new animal model based on gene - environment interactions. More specifically, we used the FSL rats as a genetic model of depression and the Flinders Resistant Line (FRL) as controls and subjected them to MS. Pups randomly assigned to the MS procedure were separated from the dam as a litter for 180min daily between postnatal day 2 to 14. On postnatal day 90, rats were weighed and sacrificed by a two second high energy focused microwave irradiation and several brain regions were obtained by micropuncture. Neurotensin like immunoreactivity (NT-LI) was measured by radioimmunoassay (RIA). The results showed that the FSL rats compared to the FRL rats have higher baseline NT-LI concentrations in the temporal cortex and periaqueductal gray and a markedly different response to maternal separation. The only observed change following maternal separation in the FRL rats was an NT-LI increase in the periaqueductal gray. In contrast, in the FSL significant increases were found in the nucleus accumbens, hippocampus, and entorhinal cortex and a decrease was seen in the temporal cortex after MS. The present study revealed baseline regional differences in NT-LI concentrations between the FSL and FRL strains and demonstrated that early MD differentially affects the two strains. The relevance of these alterations for depression as well as possible mechanisms underlying this gene-environment interaction are discussed. PMID- 27372548 TI - Practical Estimation of Amorphous Solubility Enhancement Using Thermoanalytical Data: Determination of the Amorphous/Crystalline Solubility Ratio for Pure Indomethacin and Felodipine. AB - Use of amorphous phases can mitigate the low in vivo exposures of poorly soluble, crystalline active pharmaceutical ingredients. However, it remains challenging to accurately predict the solubility enhancement offered even by a pure amorphous phase relative to the crystalline form. In this work, a methodology is presented that allows estimation of the amorphous:crystalline solubility ratio, alpha, using only measured thermodynamic quantities for each of the pure phases. With this approach, alpha values of 7.6 and 4.7 were calculated for indomethacin and felodipine, respectively, correlating more closely than previous predictions with the experimentally measured values of 4.9 and 4.7 reported in the literature. There are 3 key benefits to this approach. First, it uses simple mathematical functions to more precisely relate the temperature variations in the heat capacity (Cp) to allow a more accurate estimation of the configurational energy difference between the 2 phases, whereas traditional models typically assume that Cp of both phases are constant(s). Second, the Hoffman equation is leveraged in translating the free energy of crystal lattice formation to the actual temperature of interest (selected to be 25 degrees C/298K in this work), again, for better accuracy. Finally, as only 2 modulated differential scanning calorimetry scans are required (one for each phase), it is attractive from an experimental simplicity standpoint. PMID- 27372547 TI - Soy Phosphatidylinositol-Containing Lipid Nanoparticle Prolongs the Plasma Survival and Hemostatic Efficacy of B-domain-Deleted Recombinant Canine Factor VIII in Hemophilia A Dogs. AB - Soy phosphatidylinositol (PI)-containing lipid nanoparticles prolong plasma survival, improve hemostatic efficacy, and decrease immunogenicity of human B domain-deleted factor VIII (BDD FVIII) in hemophilia A (HA) mice. We hypothesize that PI-associated BDD FVIII is more potent than the free protein and, using mathematical modeling, have projected that PI-associated BDD FVIII could be used for once-weekly prophylactic dosing in patients. To facilitate translation to the clinic, comparative plasma survival and ex vivo efficacy of PI-associated recombinant canine FVIII (PI-rcFVIII) were evaluated in HA dogs. Two HA dogs were administered a 50-U/kg intravenous dose of free or PI-rcFVIII. rcFVIII activity measurements and ex vivo efficacy analyses such as whole blood clotting time and thromboelastography were conducted on recovered plasma and whole blood samples. PI association decreased clearance (~25%) and increased plasma exposure (~1.4 fold) of rcFVIII. PI-rcFVIII-treated animals had prolonged improvements in whole blood clotting time and thromboelastography parameters compared to free rcFVIII treated animals. Because rcFVIII is a BDD form of FVIII, these studies provide proof of principle that observations with human BDD FVIII in mice translate to higher animal species. In addition, PI-rcFVIII has potential applications in canine HA management and as a bypass therapy in inhibitor-positive HA patients. PMID- 27372549 TI - Evaluation of the Impact of Excipients and an Albendazole Salt on Albendazole Concentrations in Upper Small Intestine Using an In Vitro Biorelevant Gastrointestinal Transfer (BioGIT) System. AB - An in vitro biorelevant gastrointestinal transfer (BioGIT) system was assessed for its ability to mimic recently reported albendazole concentrations in human upper small intestine after administration of free base suspensions to fasted adults in absence and in presence of supersaturation promoting excipients (hydroxypropylmethylcellulose and lipid self-emulsifying vehicles). The in vitro method was also used to evaluate the likely impact of using the sulfate salt on albendazole concentrations in upper small intestine. In addition, BioGIT data were compared with equilibrium solubility data of the salt and the free base in human aspirates and biorelevant media. The BioGIT system adequately simulated the average albendazole gastrointestinal transfer process and concentrations in upper small intestine after administration of the free base suspensions to fasted adults. However, the degree of supersaturation observed in the duodenal compartment was greater than in vivo. Albendazole sulfate resulted in minimal increase of albendazole concentrations in the duodenal compartment of the BioGIT, despite improved equilibrium solubility observed in human aspirates and biorelevant media, indicating that the use of a salt is unlikely to lead to any significant oral absorption advantage for albendazole. PMID- 27372550 TI - Quantitative (13)C Solid-State NMR Spectra by Multiple-Contact Cross-polarization for Drug Delivery: From Active Principles to Excipients and Drug Carriers. AB - In this contribution, we present an analysis of the main parameters influencing the efficiency of the (1)H -> (13)C multiple-contact cross-polarization nuclear magnetic resonance (NMR) experiment in the context of solid pharmaceutical materials. Using the optimum experimental conditions, quantitative (13)C NMR spectra are then obtained for porous metal-organic frameworks (potential drug carriers) and for components present in drug formulations (active principle ingredient and excipients, amorphous or crystalline). Finally, we show that mixtures of components can also be quantified with this method and, hence, that it represents an ideal tool for quantification of pharmaceutical formulations by (13)C cross-polarization under magic-angle spinning NMR in the industry as it is robust and easy to set up, much faster than direct (13)C polarization and is efficient for samples at natural abundance. PMID- 27372551 TI - Regulatory Considerations of Bioequivalence Studies for Oral Solid Dosage Forms in Japan. AB - Bioequivalence (BE) studies are used to infer the therapeutic equivalence of generic drug products to original drug products throughout the world. In BE studies, bioavailability (BA) should be compared between the original and generic drug products, with BA defined as the rate and extent of absorption of active pharmaceutical ingredients or active metabolites from a product into the systemic circulation. For most of BE studies conducted during generic drug development, BA comparisons are performed in single-dose studies. In Japan, the revised "Guideline for Bioequivalence Studies of Generic Products" was made available in 2012 by the Ministry of Health, Labour, and Welfare, and generic drug development is currently conducted based on this guideline. Similarly, the U.S. Food and Drug Administration and European Medicines Agency have published guidance and guideline on generic drug development. This article introduces the guideline on Japanese BE studies for oral solid dosage forms and the dissolution tests for the similarity and equivalence evaluation between the original and generic drug products. Additionally, we discuss some of the similarities and differences in guideline between Japan, the United States, and the European Union. PMID- 27372552 TI - Interrelationships Between Structure and the Properties of Amorphous Solids of Pharmaceutical Interest. AB - This commentary explores fundamental issues associated with the structure of amorphous solids of pharmaceutical interest in terms of the effects of such structure on: various thermodynamic properties; the glass transition temperature, Tg, physical aging of glasses, polyamorphism; molecular mobility by primary diffusive and secondary Johari-Goldstein relaxations; solid-state crystallization; water vapor absorption; and the formation of active pharmaceutical ingredients-polymer dispersions. Recognizing that small organic molecules, as well as polymers used pharmaceutically, tend to exhibit highly "fragile" behavior in the supercooled liquid state, that is, significant increases in relaxation time or viscosity with decreasing temperature as Tg is approached, particular emphasis has been placed on local and global structural factors, that appear to give rise to the nonexponential dependence of the structural relaxation time and viscosity associated with spatial and temporal heterogeneity, at temperatures below the "crossover temperature," Tx, (1.2-1.4 Tg), using theoretical random close packing and "jamming" models. Utilizing a "2 region" structural model of the glassy state, wherein glasses consist of clustered domains surrounded by a higher energy and less dense "microstructure," it has been possible to better understand the underlying structural factors that give rise to a number of important phenomena which occur in the glassy state. PMID- 27372553 TI - Monosodium glutamate is not likely to be genotoxic. AB - The International Glutamate Technical Committee (IGTC) wishes to comment on a recent publication in the Journal entitled "Genotoxicity of monosodium glutamate" (authored by Ataseven N, Yuzbasioglu D, Keskin AC and Unal F) (Ataseven et al. 2016). In particular, we wish to highlight that, in our considered view, the results of this study were inappropriately discussed and that references were selectively used. PMID- 27372554 TI - LARS(r) band and tube for extensor mechanism reconstructions in proximal tibial modular endoprostheses after bone tumors. AB - Wide tumor resections around the proximal tibia (pT) are related to compromised function and high complication rates. This retrospective study aims to present the technique employed as well as functional and surgical outcomes of patients undergoing a Ligament Advanced Reinforcement System (LARS(r)) reconstruction of the knee extensor apparatus after tumor resection and modular endoprosthetic reconstruction of the proximal tibia. Twenty-five patients who received an artificial ligament after pT resection (11 men and 14 women; mean age, 29years; range 11 to 75years, with a minimum follow-up of 24months) were analyzed regarding the ISOLS failure mode classification. Twenty patients received LARS(r) during primary surgery, five patients during a revision of a pT modular endoprosthesis. LARS(r) was available as a band or a tube. The mean extension lag was nine degrees (range, 0 to 30 degrees ), the mean flexion was 103 degrees (range, 60 to 130 degrees ). The mean extension lag and active flexion in primary implanted LARS were 7.8 degrees and 101 degrees versus secondarily implanted 45 degrees and 115 degrees (p<0.0001; p=0.15). Eleven out of 14 primary implanted LARS(r) band/tubes (71%) did well with extension lag (0 to 10 degrees ). LARS(r) usage as a band or as a tube showed similar results. The estimated five-year survival of LARS(r) was 92%. The median survival of LARS(r) implanted primarily was better than in the case of secondary implantation (p=0.006). Extensor mechanism reconstruction by LARS(r) band or tube shows excellent function and satisfactory implant survival after primary reconstruction of the extensor mechanism after proximal tibia resection. We experienced no LARS(r) rupture for only mechanical reasons. LEVEL OF EVIDENCE: Level IV retrospective study. PMID- 27372555 TI - Use of a pneumatic tourniquet in total knee arthroplasty increases the risk of distal deep vein thrombosis: A prospective, randomized study. AB - BACKGROUND: There has been controversy regarding the incidence of deep vein thrombosis (DVT) after total knee arthroplasty (TKA) with or without the use of a tourniquet. The aim of this randomized, prospective study was to clarify the effects of tourniquet use on DVT in TKA. METHODS: The subjects were 109 patients scheduled to undergo TKA from April 2008 to March 2009 before the establishment of the American Association of Orthopedic Surgeons (AAOS) practice guidelines. They were randomized into two groups: 51 patients in the tourniquet group (group T) and 52 patients in the control group without a tourniquet (group C). We investigated the thrombotic presence using ultrasonography one week after surgery and compared both groups. RESULTS: There was no difference in the rate of proximal DVTs (P=0.63). However, the risk of distal DVT was significantly higher in group T than in group C (52.9% vs. 23.1%; P=0.002). CONCLUSIONS: Use of the tourniquet in TKA increased the risk of distal DVT. PMID- 27372556 TI - A prospective randomized trial evaluating two different tensioning techniques for medial patellofemoral ligament reconstruction. AB - BACKGROUND: In the literature, graft tension was mostly assessed under direct arthroscopy vision for a MPFL reconstruction. The purpose of this study was to prospectively assess the outcomes of MPFL reconstruction with graft tension of self-balance technique in comparison with arthroscopy-view technique. METHODS: Sixty patients with recurrent patellar dislocation were randomly divided into two groups to undergo MPFL reconstruction with graft tension either by the self balance technique (SB group) or the arthroscopy-view technique (AV group). At a minimum of 24months of follow up, patellar stability was evaluated with the apprehension test. Patellofemoral morphology was measured on an axial CT scan and knee function was evaluated using the Kujala and Lysholm scores. RESULTS: Twenty three patients in the SB group and 25 patients in the AV group were followed for a minimum of 24months. No recurrent dislocation or subluxation was reported. Apprehension signs remained in two patients in the SB group and in one patient in the AV group. The postoperative Kujala score for the SB group and AV group were 91.4+/-5.1 and 90.3+/-5.5, respectively, and the Lysholm score was 90.1+/-6.4 and 88.4+/-6.3, respectively, with no significant differences. On CT images, congruence angle, patellar tilt angle and lateral patellar angle were restored to the normal range. CONCLUSIONS: At a minimum of 24months of follow-up, graft tensioning using the self-balance technique yielded similar patellar stability and knee function compared with the arthroscopy-view procedure in the MPFL reconstruction. The self-balance technique as a simple procedure is recommended as a good alternative method for graft tensioning in the MPFL reconstruction. PMID- 27372557 TI - Correlation between radio-induced lymphocyte apoptosis measurements obtained from two French centres. AB - PURPOSE OF THE RESEARCH: In the era of modern treatment delivery, increasing the dose delivered to the target to improve local control might be modulated by the patient's intrinsic radio-sensitivity. A predictive assay based on radio-induced lymphocyte apoptosis quantification highlighted the significant correlation between CD4 and CD8 T-lymphocyte apoptosis and grade 2 or 3 radiation-induced late toxicities. By conducting this assay at several technical platforms, the aim of this study was to demonstrate that radio-induced lymphocyte apoptosis values obtained from two different platforms were comparable. MATERIALS AND METHODS: For 25 patients included in the PARATOXOR trial running in Dijon the radio-induced lymphocyte apoptosis results obtained from the laboratory of Montpellier (IRCM, Inserm U1194, France), considered as the reference (referred to as Lab 1), were compared with those from the laboratory located at the Institut de cancerologie de Lorraine (ICL, France), referred to as Lab 2. Different statistical methods were used to measure the agreement between the radio-induced lymphocyte apoptosis data from the two laboratories (quantitative data). The Bland-Altman plot was used to identify potential bias. RESULTS: All statistical tests demonstrated good agreement between radio-induced lymphocyte apoptosis values obtained from both sites and no major bias was identified. CONCLUSIONS: Since radio-induced lymphocyte apoptosis values, which predict tolerance to radiotherapy, could be assessed by two laboratories and showed a high level of robustness and consistency, we can suggest that this assay be extended to any laboratories that use the same technique. PMID- 27372558 TI - Analysis of rare periparotid recurrence after parotid gland-sparing intensity modulated radiotherapy for nasopharyngeal carcinoma. AB - PURPOSE: Periparotid recurrence is an uncommon phenomenon after intensity modulated radiotherapy (IMRT) for nasopharyngeal carcinoma. This study aimed to discuss the clinical characteristics, reasonable causes and feasible therapeutic modalities of patients with nasopharyngeal carcinoma and periparotid recurrence. PATIENTS AND METHODS: The medical records of 1852 patients with non-metastatic nasopharyngeal carcinoma treated with initial IMRT between January 2008 and December 2012 were retrospectively reviewed, and nine patients were finally found to have developed periparotid recurrence after IMRT. After periparotid failure, four received radiotherapy and chemotherapy, two had surgery, two had surgery and adjuvant radiotherapy or chemotherapy, and one received radiotherapy alone. RESULT: The incidence rate of periparotid recurrence was 4.90/00. According to pretreatment magnetic resonance imaging (MRI) scans, all patients had both ipsilateral retropharyngeal lymph nodes metastasis with 66.7% of extracapsular spread and level II lymphadenopathy with all extracapsular spread. The median time interval to periparotid failure was 14.8 months, and six patients were found to have a relapse in the primary sites of unsuspicious parotid nodules. After a median follow-up of 46.4 months, five patients developed distant metastasis, three of them developed local failure. In addition, one developed regional failure, one developed locoregional recurrence, and only one was alive without evidence of disease at the last follow-up. CONCLUSION: Periparotid recurrences are rare after definitive IMRT for nasopharyngeal carcinoma. However, patients with ipsilateral retropharyngeal lymph nodes or level II nodal extracapsular spread on pretreatment MRI could be suspicious of metastatic periparotid nodules. Distant metastases were the main treatment failure despite a combination of several salvage treatment of periparotid recurrence. More effective chemotherapy should be explored. PMID- 27372559 TI - Retention of Ultrasound Skills and Training in "Point-of-Care" Cardiac Ultrasound. AB - BACKGROUND: Although the growth of point-of-care ultrasound has resulted in a proliferation of teaching programs, few data exist on the maintenance of proficiency. The aim of this study was to evaluate the retention of cardiac ultrasound skills and training in physicians up to 7 years after a formal focused curriculum in residency. METHODS: Thirty internal medicine physicians, deemed proficient at graduation and having passed a practical examination that confirms imaging skills and knowledge base when a score of >=80% correct is attained, were retested. Twenty graduates (the NOPREP group) did not study any relevant material, and 10 graduates (the PREP group) were encouraged to study online videos. Scores were categorized by length of time (1-7 years) from graduates' last performance of ultrasound. RESULTS: The mean original test score of the physicians was 90 +/- 6%. With retesting NOPREP (n = 20), seven physicians were within 1 year of their last use, and five (71%) repassed the examination, scoring 80 +/- 15%. Among the remaining 13 NOPREP physicians who had >1 year of nonuse, none repassed, scoring 58 +/- 17%. In retesting PREP (n = 10), one physician was within 1 year of last use and repassed, scoring 95%. Among the remaining nine PREP physicians with >1 year since last use, three (33%) repassed (P = .05), scoring 72 +/- 21%. Diagnostic knowledge was significantly higher when good quality images were obtained. CONCLUSIONS: Learned skills in cardiac ultrasound diminish notably within 2 years of nonuse. PMID- 27372560 TI - Early Hemodynamic Improvement after Percutaneous Mitral Valve Repair Evaluated by Noninvasive Pressure-Volume Analysis. AB - BACKGROUND: Mitral regurgitation represents a volume load on the left ventricle leading to congestion and symptoms of heart failure. The aim of this study was to characterize early hemodynamic adaptions after percutaneous mitral valve (MV) repair. METHODS: Forty-six consecutive patients with symptomatic high-grade MV insufficiency (mean age, 72 years; 54% men) were prospectively included in the study and examined before and after successful catheter-based clip implantation. Seventy percent of patients had secondary mitral regurgitation. Noninvasive pressure-volume loops were reconstructed from echocardiography with simultaneous blood pressure measurements. RESULTS: MV repair reduced left ventricular end diastolic volume index from 87 +/- 41 to 80 +/- 40 mL/m(2) (P < .0001). End systolic volume index was 55 +/- 37 mL/m(2) before versus 54 +/- 37 mL/m(2) after repair (P = .52). Hence, total stroke volume decreased from 60 +/- 23 to 49 +/- 16 mL (P < .0001), as did total ejection fraction (from 41 +/- 14% to 37 +/- 13%, P = .002) and global longitudinal strain (from -11 +/- 4.9% to -9.1 +/- 4.4%, P = .0001). Forward stroke volume, forward ejection fraction, and forward cardiac output remained constant (43 +/- 12 mL vs 42 +/- 11 mL, 33 +/- 17% vs 35 +/- 18%, and 3.2 +/- 0.9 L/min vs 3.4 +/- 0.8 L/min, respectively). Parameters of left ventricular contractility (end-systolic elastance and peak power index) and measurements of afterload (arterial elastance, end-systolic wall stress, and total peripheral resistance) were similar before and after MV repair. Forward ejection fraction correlated more strongly with end-systolic elastance (r = 0.61, P < .0001) than did total ejection fraction (r = 0.35, P = .0007) or global longitudinal strain (r = -0.38, P = .0002). Total mechanical energy (pressure volume area) decreased from 10,903 +/- 4,410 to 9,124 +/- 2,968 mm Hg * mL (P = .0007) because of reduced stroke work (5,546 +/- 2,241 mm Hg * mL vs 4,414 +/- 1,412 mm Hg * mL, P < .0001). At 3 months, symptom status had improved (76% of patients in New York Heart Association classes I and II), and 97% of patients had mitral regurgitation grade <=2+. CONCLUSIONS: Left ventricular contractility and forward cardiac output remained unchanged after percutaneous MV repair despite decreases in total ejection fraction and global longitudinal strain. The left ventricle was unloaded through reduced end-diastolic volume. Thus, MV repair is associated with an improved hemodynamic state in noninvasive pressure-volume analysis. PMID- 27372561 TI - Do sex and age affect strategic behavior and inequity aversion in children? AB - The ultimatum game is commonly used to explore fairness in adults in bargaining situations. Although the changes in responses that occur during development have been investigated in children, the results have been mixed. Whereas some studies show that proposers offer more when they grow older, others indicate the opposite. Moreover, these studies are outcome-based and leave intentions out of the scene, although intentions play a relevant role in daily life. The mini ultimatum game offers the opportunity to test both outcomes and intentions, but one major obstacle for accurately pinpointing developmental transitions in strategic behavior and inequity aversion so far has been the multiple confounds that have plagued previous studies, including different methods, small sample sizes, and reduced age differences. We administered an anonymous direct-method one-shot mini-ultimatum game to 478 6- and 10-year-old children. Strategic behavior was present at 10 years of age; older participants matched more accurately what responders would accept than younger participants. However, this was true only for older girls. No sex differences were detected in younger children. No age group seemed to consider the proposer's intentions given that the rejections of the default option were not significant across conditions. Both disadvantageous and advantageous inequity aversions were present in 6-year-olds. However, older children exhibited significantly more disadvantageous inequity aversion than younger children. This contrast made the pattern of rejection of 6 year-olds look more similar to the pattern of rejection found in adults. No sex differences were found in responders' behavior. PMID- 27372562 TI - Clinicopathologic Features of Translocation Renal Cell Carcinoma. AB - BACKGROUND: Translocation renal cell carcinomas (TFE3 RCC) are associated with variable genetic rearrangements of the TFE3 gene on chromosome Xp11.2. Translocation tumors represent 1% to 5% of all cases of RCC, with the greatest frequency among children and young adults. We sought to characterize the clinicopathologic features of translocation RCC at a Middle Eastern institution. MATERIALS AND METHODS: The clinical and pathologic data from a single institution were retrospectively reviewed. A total of 14 patients with translocation RCC had been diagnosed from 2005 to 2014. The outcome measures included patient characteristics, clinical manifestations, pathologic features, treatment outcomes, cancer-specific survival, and progression-free survival. RESULTS: The mean age at diagnosis was 35 years. Of the 14 patients, 5 were female. Translocation RCC was an incidental diagnosis for all but 2 of the 14 patients. The mean tumor size was 9 cm; 1 patient had bilateral tumors, and 3 presented with positive lymph nodes. Three patients underwent partial nephrectomy. Three patients had developed metastasis at 4 months, 5 months, and 3 years after diagnosis. One patent had died 4 months after surgery and one had died 21 months after surgery (both of metastases). The disease-free survival rate was 71% at a mean follow-up of 31 months. CONCLUSION: Translocation RCC is a rare and potentially aggressive subtype of kidney cancer. An overall survival of > 3 years has been noted, unless metastasis is present at diagnosis. PMID- 27372563 TI - Anti-hIgE gene therapy of peanut-induced anaphylaxis in a humanized murine model of peanut allergy. AB - BACKGROUND: Peanuts are the most common food to provoke fatal or near-fatal anaphylactic reactions. Treatment with an anti-hIgE mAb is efficacious but requires frequent parenteral administration. OBJECTIVE: Based on the knowledge that peanut allergy is mediated by peanut-specific IgE, we hypothesized that a single administration of an adeno-associated virus (AAV) gene transfer vector encoding for anti-hIgE would protect against repeated peanut exposure in the host with peanut allergy. METHODS: We developed a novel humanized murine model of peanut allergy that recapitulates the human anaphylactic response to peanuts in NOD-scid IL2Rgammanull mice transferred with blood mononuclear cells from donors with peanut allergy and then sensitized with peanut extract. As therapy, we constructed an adeno-associated rh.10 serotype vector coding for a full-length, high-affinity, anti-hIgE antibody derived from the Fab fragment of the anti-hIgE mAb omalizumab (AAVrh.10anti-hIgE). In the reconstituted mice peanut-specific IgE was induced by peanut sensitization and hypersensitivity, and reactions were provoked by feeding peanuts to mice with symptoms similar to those of human subjects with peanut allergy. RESULTS: A single administration of AAVrh.10anti hIgE vector expressed persistent levels of anti-hIgE. The anti-hIgE vector, administered either before sensitization or after peanut sensitization and manifestation of the peanut-induced phenotype, blocked IgE-mediated alterations in peanut-induced histamine release, anaphylaxis scores, locomotor activity, and free IgE levels and protected animals from death caused by anaphylaxis. CONCLUSION: If this degree of persistent efficacy translates to human subjects, AAVrh.10anti-hIgE could be an effective 1-time preventative therapy for peanut allergy and possibly other severe, IgE-mediated allergies. PMID- 27372564 TI - Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization. AB - BACKGROUND: Programmed death 1 (PD-1) is an immunologic checkpoint that limits immune responses by delivering potent inhibitory signals to T cells on interaction with specific ligands expressed on tumor/virus-infected cells, thus contributing to immune escape mechanisms. Therapeutic PD-1 blockade has been shown to mediate tumor eradication with impressive clinical results. Little is known about the expression/function of PD-1 on human natural killer (NK) cells. OBJECTIVE: We sought to clarify whether human NK cells can express PD-1 and analyze their phenotypic/functional features. METHODS: We performed multiparametric cytofluorimetric analysis of PD-1+ NK cells and their functional characterization using degranulation, cytokine production, and proliferation assays. RESULTS: We provide unequivocal evidence that PD-1 is highly expressed (PD-1bright) on an NK cell subset detectable in the peripheral blood of approximately one fourth of healthy subjects. These donors are always serologically positive for human cytomegalovirus. PD-1 is expressed by CD56dim but not CD56bright NK cells and is confined to fully mature NK cells characterized by the NKG2A-KIR+CD57+ phenotype. Proportions of PD-1bright NK cells were higher in the ascites of a cohort of patients with ovarian carcinoma, suggesting their possible induction/expansion in tumor environments. Functional analysis revealed a reduced proliferative capability in response to cytokines, low degranulation, and impaired cytokine production on interaction with tumor targets. CONCLUSIONS: We have identified and characterized a novel subpopulation of human NK cells expressing high levels of PD-1. These cells have the phenotypic characteristics of fully mature NK cells and are increased in patients with ovarian carcinoma. They display low proliferative responses and impaired antitumor activity that can be partially restored by antibody-mediated disruption of PD-1/programmed death ligand interaction. PMID- 27372565 TI - Opposing functions of thymic stromal lymphopoietin-responsive basophils and dendritic cells in a mouse model of atopic dermatitis. PMID- 27372566 TI - CD23 surface density on B cells is associated with IgE levels and determines IgE facilitated allergen uptake, as well as activation of allergen-specific T cells. AB - BACKGROUND: Increasing evidence suggests that the low-affinity receptor for IgE, CD23, plays an important role in controlling the activity of allergen-specific T cells through IgE-facilitated allergen presentation. OBJECTIVE: We sought to determine the number of CD23 molecules on immune cells in allergic patients and to investigate whether the number of CD23 molecules on antigen-presenting cells is associated with IgE levels and influences allergen uptake and allergen specific T-cell activation. METHODS: Numbers of CD23 molecules on immune cells of allergic patients were quantified by using flow cytometry with QuantiBRITE beads and compared with total and allergen-specific IgE levels, as well as with allergen-induced immediate skin reactivity. Allergen uptake and allergen-specific T-cell activation in relation to CD23 surface density were determined by using flow cytometry in combination with confocal microscopy and T cells transfected with the T-cell receptor specific for the birch pollen allergen Bet v 1, respectively. Defined IgE-allergen immune complexes were formed with human monoclonal allergen-specific IgE and Bet v 1. RESULTS: In allergic patients the vast majority of CD23 molecules were expressed on naive IgD+ B cells. The density of CD23 molecules on B cells but not the number of CD23+ cells correlated with total IgE levels (RS = 0.53, P = .03) and allergen-induced skin reactions (RS = 0.63, P = .008). Uptake of allergen-IgE complexes into B cells and activation of allergen-specific T cells depended on IgE binding to CD23 and were associated with CD23 surface density. Addition of monoclonal IgE to cultured PBMCs significantly (P = .04) increased CD23 expression on B cells. CONCLUSION: CD23 surface density on B cells of allergic patients is correlated with allergen specific IgE levels and determines allergen uptake and subsequent activation of T cells. PMID- 27372567 TI - Traffic-related air pollution exposure is associated with allergic sensitization, asthma, and poor lung function in middle age. AB - BACKGROUND: Traffic-related air pollution (TRAP) exposure is associated with allergic airway diseases and reduced lung function in children, but evidence concerning adults, especially in low-pollution settings, is scarce and inconsistent. OBJECTIVES: We sought to determine whether exposure to TRAP in middle age is associated with allergic sensitization, current asthma, and reduced lung function in adults, and whether these associations are modified by variants in Glutathione S-Transferase genes. METHODS: The study sample comprised the proband 2002 laboratory study of the Tasmanian Longitudinal Health Study. Mean annual residential nitrogen dioxide (NO2) exposure was estimated for current residential addresses using a validated land-use regression model. Associations between TRAP exposure and allergic sensitization, lung function, current wheeze, and asthma (n = 1405) were investigated using regression models. RESULTS: Increased mean annual NO2 exposure was associated with increased risk of atopy (adjusted odds ratio [aOR], 1.14; 95% CI, 1.02-1.28 per 1 interquartile range increase in NO2 [2.2 ppb]) and current wheeze (aOR, 1.14; 1.02-1.28). Similarly, living less than 200 m from a major road was associated with current wheeze (aOR, 1.38; 95% CI, 1.06-1.80) and atopy (aOR, 1.26; 95% CI, 0.99-1.62), and was also associated with having significantly lower prebronchodilator and postbronchodilator FEV1 and prebronchodilator forced expiratory flow at 25% to 75% of forced vital capacity. We found evidence of interactions between living less than 200 m from a major road and GSTT1 polymorphism for atopy, asthma, and atopic asthma. Overall, carriers of the GSTT1 null genotype had an increased risk of asthma and allergic outcomes if exposed to TRAP. CONCLUSIONS: Even relatively low TRAP exposures confer an increased risk of adverse respiratory and allergic outcomes in genetically susceptible individuals. PMID- 27372568 TI - Predominant Api m 10 sensitization as risk factor for treatment failure in honey bee venom immunotherapy. AB - BACKGROUND: Component resolution recently identified distinct sensitization profiles in honey bee venom (HBV) allergy, some of which were dominated by specific IgE to Api m 3 and/or Api m 10, which have been reported to be underrepresented in therapeutic HBV preparations. OBJECTIVE: We performed a retrospective analysis of component-resolved sensitization profiles in HBV allergic patients and association with treatment outcome. METHODS: HBV-allergic patients who had undergone controlled honey bee sting challenge after at least 6 months of HBV immunotherapy (n = 115) were included and classified as responder (n = 79) or treatment failure (n = 36) on the basis of absence or presence of systemic allergic reactions upon sting challenge. IgE reactivity to a panel of HBV allergens was analyzed in sera obtained before immunotherapy and before sting challenge. RESULTS: No differences were observed between responders and nonresponders regarding levels of IgE sensitization to Api m 1, Api m 2, Api m 3, and Api m 5. In contrast, Api m 10 specific IgE was moderately but significantly increased in nonresponders. Predominant Api m 10 sensitization (>50% of specific IgE to HBV) was the best discriminator (specificity, 95%; sensitivity, 25%) with an odds ratio of 8.444 (2.127-33.53; P = .0013) for treatment failure. Some but not all therapeutic HBV preparations displayed a lack of Api m 10, whereas Api m 1 and Api m 3 immunoreactivity was comparable to that of crude HBV. In line with this, significant Api m 10 sIgG4 induction was observed only in those patients who were treated with HBV in which Api m 10 was detectable. CONCLUSIONS: Component-resolved sensitization profiles in HBV allergy suggest predominant IgE sensitization to Api m 10 as a risk factor for treatment failure in HBV immunotherapy. PMID- 27372569 TI - Do we really need asthma-chronic obstructive pulmonary disease overlap syndrome? AB - The association of asthma and chronic obstructive pulmonary disease (COPD) in the same patient, which is designated as mixed asthma-COPD phenotype or overlap syndrome (ACOS), remains a controversial issue. This is primarily because many conflicting aspects in the definition of ACOS remain, and it is extremely difficult to summarize the distinctive features of this syndrome. Furthermore, we are realizing that asthma, COPD, and ACOS are not single diseases but rather syndromes consisting of several endotypes and phenotypes and, consequently, comprising a spectrum of diseases. The umbrella term ACOS blurs the lines between asthma and COPD and allows an approach that simplifies therapy. However, this approach contradicts the modern concept according to which we must move toward more targeted and personalized therapies to treat patients with these diseases. Therefore we argue that the term ACOS must be abandoned and ultimately replaced when new phenotypes and underlying endotypes are identified and a new taxonomy of airway diseases is generated. PMID- 27372571 TI - Facile synthesis of a ratiometric oxygen nanosensor for cellular imaging. AB - A new type of cell-penetrating ratiometric fluorescence oxygen sensing nanoparticle was prepared through a facile co-precipitation method. Amphiphilic polymer poly (styrene-co-maleic anhydride) (PSMA) was firstly cooperated with polystyrene (PS) to envelop the highly photostable phosphorescent oxygen indicator, platinum(II)-tetrakis(pentafluorophenyl)porphyrin (PtTFPP, emission at 648nm), and the reference fluorophore, poly(9, 9-dioctylfluorene) (PFO, emission at 440nm ), via hydrophobic interaction in aqueous solution. To improve the sensor biocompatibility, the biomacromolecule poly-l-lysine (PLL) was selected to act as a shell via electrostatic forces. The as-prepared PtTFPP doped core-shell nanoparticles (called PPMA/PLL NPs) exhibited an excellent ratiometric luminescence response to O2 content with high quenching efficiency and full reversibility in the oxygen sensing. More importantly, these oxygen nanosensors passed across the cell membrane after co-incubation without external force. Labeled cells exhibited high brightness in the matching blue and red channels of a digital camera. And most nanosensors were found locating in cytoplasm rather than being trapped in endosomes. PMID- 27372570 TI - IL-33 promotes food anaphylaxis in epicutaneously sensitized mice by targeting mast cells. AB - BACKGROUND: Cutaneous exposure to food allergens predisposes to food allergy, which is commonly associated with atopic dermatitis (AD). Levels of the epithelial cytokine IL-33 are increased in skin lesions and serum of patients with AD. Mast cells (MCs) play a critical role in food-induced anaphylaxis and express the IL-33 receptor ST2. The role of IL-33 in patients with MC-dependent food anaphylaxis is unknown. OBJECTIVE: We sought to determine the role and mechanism of action of IL-33 in patients with food-induced anaphylaxis in a model of IgE-dependent food anaphylaxis elicited by oral challenge of epicutaneously sensitized mice. METHODS: Wild-type, ST2-deficient, and MC-deficient KitW-sh/W-sh mice were epicutaneously sensitized with ovalbumin (OVA) and then challenged orally with OVA. Body temperature was measured by means of telemetry, Il33 mRNA by means of quantitative PCR, and IL-33, OVA-specific IgE, and mouse mast cell protease 1 by means of ELISA. Bone marrow-derived mast cell (BMMC) degranulation was assessed by using flow cytometry. RESULTS: Il33 mRNA expression was upregulated in tape-stripped mouse skin and scratched human skin. Tape stripping caused local and systemic IL-33 release in mice. ST2 deficiency, as well as ST2 blockade before oral challenge, significantly reduced the severity of oral anaphylaxis without affecting the systemic TH2 response to the allergen. Oral anaphylaxis was abrogated in KitW-sh/W-sh mice and restored by means of reconstitution with wild-type but not ST2-deficient BMMCs. IL-33 significantly enhanced IgE-mediated degranulation of BMMCs in vitro. CONCLUSION: IL-33 is released after mechanical skin injury, enhances IgE-mediated MC degranulation, and promotes oral anaphylaxis after epicutaneous sensitization by targeting MCs. IL-33 neutralization might be useful in treating food-induced anaphylaxis in patients with AD. PMID- 27372572 TI - Biomimetic nanochannels based biosensor for ultrasensitive and label-free detection of nucleic acids. AB - A very simple sensing device based on biomimetic nanochannels has been developed for label-free, ultrasensitive and highly sequence-specific detection of DNA. Probe DNA was modified on the inner wall of the nanochannel surface by layer-by layer (LBL) assembly. After probe DNA immobilization, DNA detection was realized by monitoring the rectified ion current when hybridization occurred. Due to three dimensional (3D) nanoscale environment of the nanochannel, this special geometry dramatically increased the surface area of the nanochannel for immobilization of probe molecules on the inner-surface and enlarged contact area between probes and target-molecules. Thus, the unique sensor reached a reliable detection limit of 10 fM for target DNA. In addition, this DNA sensor could discriminate complementary DNA (c-DNA) from non-complementary DNA (nc-DNA), two-base mismatched DNA (2bm-DNA) and one-base mismatched DNA (1bm-DNA) with high specificity. Moreover, the nanochannel-based biosensor was also able to detect target DNA even in an interfering environment and serum samples. This approach will provide a novel biosensing platform for detection and discrimination of disease-related molecular targets and unknown sequence DNA. PMID- 27372573 TI - Simultaneous and multiplexed detection of exosome microRNAs using molecular beacons. AB - Simultaneous and multiplexed detection of microRNAs (miRNAs) in a whole exosome is developed, which can be utilized as a PCR-free efficient diagnosis method for various diseases. Exosomes are small extracellular vesicles that contain biomarker miRNAs from parental cells. Because they circulate throughout bodily fluids, exosomal biomarkers offer great advantages for diagnosis in many aspects. In general, PCR-based methods can be used for exosomal miRNA detection but they are laborious, expensive, and time-consuming, which make them unsuitable for high throughput diagnosis of diseases. Previously, we reported that single miRNA in the exosomes can be detected specifically using an oligonucleotide probe or molecular beacon. Herein, we demonstrate for the first time that multiple miRNAs can be detected simultaneously in exosomes using miRNA-targeting molecular beacons. Exosomes from a breast cancer cell line, MCF-7, were used for the production of exosomes because MCF-7 has a high level of miR-21, miR-375, and miR 27a as target miRNAs. Molecular beacons successfully hybridized with multiple miRNAs in the cancer cell-derived exosomes even in the presence of high human serum concentration. In addition, it is noteworthy that the choice of fluorophores for multiplexing biomarkers in an exosome is crucial because of its small size. The proposed method described in this article is beneficial to high throughput analysis for disease diagnosis, prognosis, and response to treatment because it is a time-, labor-, and cost-saving technique. PMID- 27372574 TI - Peptidic beta-sheet binding with Congo Red allows both reduction of error variance and signal amplification for immunoassays. AB - Although conventional enzyme-linked immunosorbent assays (ELISA) and related assays have been widely applied for the diagnosis of diseases, many of them suffer from large error variance for monitoring the concentration of targets over time, and insufficient limit of detection (LOD) for assaying dilute targets. We herein report a readout mode of ELISA based on the binding between peptidic beta sheet structure and Congo Red. The formation of peptidic beta-sheet structure is triggered by alkaline phosphatase (ALP). For the detection of P-Selectin which is a crucial indicator for evaluating thrombus diseases in clinic, the 'beta-sheet and Congo Red' mode significantly decreases both the error variance and the LOD (from 9.7ng/ml to 1.1 ng/ml) of detection, compared with commercial ELISA (an existing gold-standard method for detecting P-Selectin in clinic). Considering the wide range of ALP-based antibodies for immunoassays, such novel method could be applicable to the analysis of many types of targets. PMID- 27372575 TI - Chondrosarcoma of the small toe in an adult with Down syndrome. PMID- 27372576 TI - The tax-free year in Iceland: A natural experiment to explore the impact of a short-term increase in labor supply on the risk of heart attacks. AB - Evidence is mixed on whether society-wide economic conditions affect cardiovascular health and the reasons for the suggested relationship are largely untested. We explore whether a short-term increase in labor supply affects the probability of acute myocardial infarctions, using a natural experiment in Iceland. In 1987 personal income taxes were temporarily reduced to zero, resulting in an overall increase in labor supply. We merge and analyze individual level, registry-based data on earnings and AMIs including all Icelandic men and women aged 45-74 during the period 1982-1992. The results support the prominent hypothesis of increased work as a mechanism explaining worsening heart health in upswings, for men aged 45-64 who were self-employed. We furthermore find a larger increase in probability of AMIs during the tax-free year in men aged 45-54 than men aged 55-64. PMID- 27372577 TI - The anticipatory effects of Medicare Part D on drug utilization. AB - While health care policies are frequently signed into law well before they are implemented, such lags are ignored in most empirical work. This paper demonstrates the importance of implementation lags in the context of Medicare Part D, the prescription drug benefit that took effect two years after it was signed into law. Exploiting the differential responses of chronic and acute drugs to anticipated future prices, I show that individuals reduced drug utilization for chronic but not acute drugs in anticipation of Part D's implementation. Accounting for this anticipatory response substantially reduces the estimated total treatment effect of Part D. PMID- 27372578 TI - Integration of genomic and proteomic data to identify candidate genes in HT-29 cells after incubation with Bifidobacterium bifidum ATCC 29521. AB - As the predominant group inhabiting the human gastrointestinal tract, bifidobacteria play a vital role in human nutrition, therapeutics, and health by shaping and maintaining the gut ecosystem, reducing blood cholesterol, and promoting the supply of nutrients. The interaction between bacterial cells and human intestinal epithelial cell lines has been studied for decades in an attempt to understand the mechanisms of action. These studies, however, have been limited by lack of genomic and proteomic database to aid in achieving comprehensive understanding of these mechanisms at molecular levels. Microarray data (GSE: 74119) coupled with isobaric tags for relative and absolute quantitation (iTRAQ) were performed to detect differentially expressed genes and proteins in HT-29 cells after incubation with Bifidobacterium bifidum. Real-time quantitative PCR, gene ontology, and Kyoto Encyclopedia of Genes and Genomes analyses were further conducted for mRNA validation, functional annotation, and pathway identification, respectively. According to the results of microarray, 1,717 differentially expressed genes, including 1,693 upregulated and 24 downregulated genes, were selected and classified by the gene ontology database. The iTRAQ analysis identified 43 differentially expressed proteins, where 29 proteins were upregulated and 14 proteins were downregulated. Eighty-two candidate genes showing consistent differences with microarray and iTRAQ were further validated in HT-29 and Caco-2 cells by real-time quantitative PCR. Nine of the top genes showing interesting results with high confidence were further investigated in vivo in mice intestine samples. Integration of genomic and proteomic data provides an approach to identify candidate genes that are more likely to function in ubiquitin-mediated proteolysis, positive regulation of apoptosis, membrane proteins, and transferase catalysis. These findings might contribute to our understanding of molecular mechanisms regulating the interaction between probiotics and intestinal epithelial cell lines. PMID- 27372579 TI - Characterization and adsorption of Lactobacillus virulent phage P1. AB - Bacteriophage infection of lactic acid bacteria is considered an important problem worldwide in the food fermentation industry, as it may produce low quality or unsafe foods, cause fermentation failure, and result in economic losses. To increase current knowledge on the properties of Lactobacillus virulent phages, we evaluated the effect of divalent cations, temperature, pH, and chloramphenicol on the adsorption ability of Lactobacillus virulent phage P1. Phage P1 was isolated from the abnormal fermentation liquid of Lactobacillus plantarum IMAU10120. The results showed that this phage belonged to the Siphoviridae family. The latent period of this phage was 45min, and the burst time was 90min. Burst size was 132.88+/-2.37 phage counts expressed per milliliter per infective center. This phage showed good tolerance at different temperatures, but incubation at 50 degrees C only affected its adsorption. Adsorption rate reached a maximum value between 30 and 42 degrees C. A high adsorption value of phage infectivity was obtained from pH 6 to 8. Moreover, calcium ions promoted and increased the adsorption capacity of phage P1, but magnesium ions had negative effects. Chloramphenicol had no effect on phage adsorption. This study increased current knowledge on the characterization and biological aspects of Lactobacillus virulent phages, and may provide some basic information that can be used to design successful antiphage strategies in the food industry. PMID- 27372580 TI - Use of on-farm data to guide treatment and control mastitis caused by Streptococcus uberis. AB - Treatment of mastitis is the most common reason for use of antimicrobial agents in dairy cattle. The responsible use of antimicrobials could be strengthened by knowledge of predictors for cure, which would help to tailor treatment decisions. Ideally, to allow for widespread uptake, this would be achieved using data that are routinely available. To assess whether this is feasible in practice, farmers were invited to submit milk samples from mastitis cases to their veterinary practice for bacteriological culture. Among 624 culture-positive samples, 251 were positive for Streptococcus uberis. Using cow-level data, cases were classified as severe, first nonsevere, repeat, or subclinical. Additional data were collected at the cow level [somatic cell count (SCC), parity, lactation stage, milk yield, fat and protein contents, treatment] and at the herd level (housing, bedding, premilking teat disinfection, postmilking teat disinfection). Severe cases were overrepresented among heifers and animals in early lactation, and repeat cases were overrepresented in cows with 3 or more lactations. The probability of cure was higher among first- and second-parity animals than among older cows, and was higher in animals with a single elevated cow-level SCC than in animals with multiple high SCC records. Results obtained in the current study are similar to those previously described for Staphylococcus aureus mastitis. Thus, routinely available cow-level information can help to predict the outcome of antimicrobial treatment of the most common causes of gram-positive mastitis. PMID- 27372581 TI - Genetic parameters for dry matter intake in primiparous Holstein, Nordic Red, and Jersey cows in the first half of lactation. AB - Dry matter intake (DMI) is a key component of feed efficiency in dairy cattle. In this study, we estimated genetic parameters of DMI over the first 24 lactation weeks in 3 dairy cattle breeds: Holstein, Nordic Red, and Jersey. In total, 1,656 primiparous cows (717 Holstein, 663 Nordic Red, and 276 Jersey) from Denmark, Finland, and Sweden were studied. For each breed, variance components, heritability, and repeatability for weekly DMI were estimated in 6 consecutive periods of the first 24 lactation weeks based on a repeatability animal model. Genetic correlations for DMI between different lactation periods were estimated using bivariate models. Based on our results, Holstein and Nordic Red cows had similar DMI at the beginning of lactation, but later in lactation Holstein cows had a slightly higher DMI than Nordic Red cows. In comparison, Jersey cows had a significantly lower DMI than the other 2 breeds within the first 24 lactation weeks. Heritability estimates for DMI ranged from 0.20 to 0.40 in Holsteins, 0.25 to 0.41 in Nordic Red, and 0.17 to 0.42 in Jerseys within the first 24 lactation weeks. Genetic and phenotypic variances for DMI varied along lactation within each breed and tended to be higher in the middle of lactation than at the beginning of the lactation. High genetic correlations were noted for DMI in lactation wk 5 to 24 in all 3 breeds, whereas DMI at early lactation (lactation wk 1 to 4) tended to be genetically different from DMI in the middle of lactation. The 3 breeds in this study might differ in their genetic variances for DMI, but the differences were not statistically significant in most of the studied periods. Breed differences for the genetic variance tended to be more obvious than for heritability. The potential breed differences in genetic variation for DMI should be considered in a future study using feed intake information from multiple breeds. PMID- 27372582 TI - Short communication: Initial evidence supporting existence of potential rumen epidermal stem and progenitor cells. AB - The bovine rumen epidermis is a keratinized multilayered tissue that experiences persistent cell turnover. Because of this constant cell turnover, epidermal stem cells and their slightly more differentiated daughter cells, epidermal progenitor cells, must exist in the stratum basale of rumen epidermis. To date, these 2 epidermal cell populations and any unique cellular markers they may possess remain completely uncharacterized in the bovine rumen. An important first step in this new research area is the demonstration of the relative abundance and existence of markers for these cells in rumen tissue. A related second step is to document rumen epidermal proliferative responses to an extrinsic signal such as nutrient concentration within the rumen. The objectives of this experiment were to evaluate the extrinsic effect of diet on (1) gene expression of 6 potential rumen epidermal stem or progenitor cell markers and (2) rumen epidermal cell proliferation within the stratum basale. Twelve preweaned Holstein heifers were fed either a restricted diet (R) or an enhanced diet (EH). Animals on R received a milk replacer (MR) diet fed at 0.44kg of powder dry matter (DM)/d (20.9% crude protein, 29.8% fat, DM basis) and EH received MR at 1.08kg of powder dry matter/d (28.9% crude protein, 26.2% fat, DM basis). All calves had access to a 20% crude protein starter and were weaned during wk 7 of the experiment. Lifetime DM intake was 0.73kg of DM/calf per day for R (5.88 Mcal of net energy/calf per day) and 1.26kg of DM/calf per day for EH (10.68 Mcal of net energy/calf per day). Twenty four hours before slaughter heifers received an intravenous dose of 5-bromo-2' deoxyuridine to label proliferating cells. Heifers were slaughtered at 8 wk of age, and rumen samples from the ventral sac region were obtained and stored in RNA preservative and processed for routine histology. Quantitative real-time reverse transcriptase PCR was used to analyze relative abundance of genes. Candidate genes for markers of epidermal stem and progenitor cells were beta1 integrin (ITGB1), tumor protein p63 (TP63), keratin-14 (KRT14), Notch-1 (NOTCH1), Leu-rich repeat-containing G protein-coupled receptor 5-expressing (LGR5), and musashi-1 (MSI1). All genes were detected in the rumen tissue; ITGB1 was increased in EH compared with R. 5-Bromo-2'-deoxyuridine immunohistochemistry revealed that both R and EH rumen tissue had proliferating cells within the stratum basale of the rumen epidermis at the time of analysis. The EH diet resulted in an additive effect on cell proliferation. The percentage of cells in the stratum basale synthesizing DNA in preparation for mitosis nearly doubled (23.8+/-2.4% for EH vs. 14.7+/-2.0% for R) compared with calves fed R. This work represents the first attempt at characterizing rumen epidermal stem and progenitor cells. We demonstrated the relative abundance and existence of potential markers in rumen tissue and showed a rumen epidermal proliferative response to the extrinsic stimulus of nutrient concentration in the form of diet. PMID- 27372583 TI - Use of rumination and activity monitoring for the identification of dairy cows with health disorders: Part III. Metritis. AB - The objectives of this study were to evaluate (1) the performance of an automated health-monitoring system (AHMS) to identify cows with metritis based on an alert system (health index score, HIS) that combines rumination time and physical activity; (2) the number of days between the first HIS alert and clinical diagnosis (CD) of metritis by farm personnel; and (3) the daily rumination time, physical activity, and HIS patterns around CD. In this manuscript, the overall performance of HIS to detect cows with all disorders of interest in this study [ketosis, displaced abomasum, indigestion (companion paper, part I), mastitis (companion paper, part II), and metritis] is also reported. Holstein cattle (n=1,121; 451 nulliparous and 670 multiparous) were fitted with a neck-mounted electronic rumination and activity monitoring tag (HR Tags, SCR Dairy, Netanya, Israel) from at least -21 to 80 d in milk (DIM). Raw data collected in 2-h periods were summarized per 24 h as daily rumination and activity. An HIS (0 to 100 arbitrary units) was calculated daily for individual cows with an algorithm that used rumination and activity. A positive HIS outcome was defined as an HIS of <86 units during at least 1 d from -5 to 2 d after CD. Blood concentrations of nonesterified fatty acids, beta-hydroxybutyrate, total calcium, and haptoglobin were determined in a subgroup of cows (n=459) at -11+/-3, -4+/-3, 0, 3+/-1, 7+/ 1, 14+/-1, and 28+/-1 DIM. The overall sensitivity of HIS was 55% for all cases of metritis (n=349), but it was greater for cows with metritis and another disorder (78%) than for cows with metritis only (53%). Cows diagnosed with metritis and flagged based on HIS had substantial alterations in their rumination, activity, and HIS patterns around CD, alterations of blood markers of metabolic and health status around calving, reduced milk production, and were more likely to exit the herd than cows not flagged based on the HIS and cows without disease, suggesting that cows flagged based on the HIS had a more severe episode of metritis. Including all disorders of interest for this study, the overall sensitivity was 59%, specificity was 98%, positive predictive value was 58%, negative predictive value was 98%, and accuracy was 96%. The AHMS was effective for identifying cows with severe cases of metritis, but less effective for identifying cows with mild cases of metritis. Also, the overall accuracy and timing of the AHMS alerts for cows with health disorders indicated that AHMS that combine rumination and activity could be a useful tool for identifying cows with metabolic and digestive disorders, and more severe cases of mastitis and metritis. PMID- 27372584 TI - Use of rumination and activity monitoring for the identification of dairy cows with health disorders: Part II. Mastitis. AB - The objectives of this study were to evaluate (1) the performance of an automated health-monitoring system (AHMS) to identify cows with mastitis based on an alert system (health index score, HIS) that combines rumination time and physical activity; (2) the number of days between the first HIS alert and clinical diagnosis (CD) of mastitis by farm personnel; and (3) the daily rumination time, physical activity, and HIS patterns around CD. Holstein cows (n=1,121; 451 nulliparous and 670 multiparous) were fitted with a neck-mounted electronic rumination and activity monitoring tag (HR Tags, SCR Dairy, Netanya, Israel.) from at least -21 to 80 d in milk (DIM). Raw data collected in 2-h periods were summarized per 24 h as daily rumination and activity. An HIS (0 to 100 arbitrary units) was calculated daily for individual cows with an algorithm that used rumination and activity. A positive HIS outcome was defined as an HIS of <86 units during at least 1 d from -5 to 2 d after CD. Blood concentrations of nonesterified fatty acids, beta-hydroxybutyrate, total calcium, and haptoglobin were also determined in a subgroup of cows (n=459) at -11+/-3, -4+/-3, 0, 3+/-1, 7+/-1, 14+/-1, and 28+/-1 DIM. The sensitivity of the HIS was 58% [95% confidence interval (CI): 49, 67] for all cases of clinical mastitis (n=123), and 55% (95% CI: 46, 64; n=114) and 89% (95% CI: 68, 100; n=9) for cases of mastitis alone or concurrent with other health disorders, respectively. Among clinical cases, sensitivity was 80.7% (95% CI: 67, 97) for cases caused by Escherichia coli (n=31) and ranged from 45 to 48% for cases caused by gram-positive bacteria (n=39; Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus uberis, Streptococcus spp., Staphylococcus spp., and Trueperella pyogenes), Staphylococcus aureus (n=11), or cases with no bacterial growth (n=25). Days between the first HIS <86 and CD were -0.6 (95% CI: -1.1, -0.2) for all cases of mastitis. Cows diagnosed with mastitis had alterations of their rumination, activity, HIS patterns, and reduced milk production around CD depending on the type of mastitis case. Cows with mastitis also had some alterations of their calcium and haptoglobin concentrations around calving. The AHMS used in this study was effective for identifying cows with clinical cases of mastitis caused by E. coli and cows with another disease occurring during an event of mastitis, but it was less effective in identifying cows with mastitis not caused by E. coli. PMID- 27372585 TI - Precision-feeding dairy heifers a high rumen-degradable protein diet with different proportions of dietary fiber and forage-to-concentrate ratios. AB - The objective of this experiment was to determine the effects of feeding a high rumen-degradable protein (RDP) diet when dietary fiber content is manipulated within differing forage-to-concentrate ratio (F:C) on nutrient utilization of precision-fed dairy heifers. Six cannulated Holstein heifers (486.98+/-15.07kg of body weight) were randomly assigned to 2 F:C, low- (45% forage; LF) and high forage (90% forage; HF) diets and to a fiber proportion sequence [33% grass hay and wheat straw (HS), 67% corn silage (CS; low fiber); 50% HS, 50% CS (medium fiber); and 67% HS, 33% CS (high fiber)] within forage proportion administered according to a split-plot, 3*3 Latin square design (16-d periods). Heifers fed LF had greater apparent total-tract organic matter digestibility coefficients (dC), neutral detergent fiber, and cellulose than those fed LC diets. Substituting CS with HS resulted in a linear reduction in dry matter, organic matter, and cellulose dC. Nitrogen dC was not different between F:C or with increasing proportions of HS in diets, but N retention tended to decrease linearly as HS was increased in the diets. Predicted microbial protein flow to the duodenum decreased linearly with HS addition and protozoa numbers HS interacted linearly, exhibiting a decrease as HS increased for LF, whereas no effects were observed for HF. Blood urea N increased linearly as HS was incorporated. The LF-fed heifers had a greater ruminal volatile fatty acids concentration. We noted a tendency for a greater dry matter, and a significantly higher liquid fraction turnover rate for HF diets. There was a linear numerical increase in the liquid and solid fraction turnover rate as fiber was added to the diets. Rumen fermentation parameters and fractional passages (solid and liquid) rates support the reduction in dC, N retention, and microbial protein synthesis observed as more dietary fiber is added to the rations of dairy heifers precision-fed a constant proportion of rumen-degradable protein. PMID- 27372586 TI - Feeding a higher plane of nutrition and providing exogenous estrogen increases mammary gland development in Holstein heifer calves. AB - Feeding heifers a higher plane of nutrition postweaning but before puberty can negatively affect mammary gland development and future milk yield. However, enhanced nutrition preweaning may promote development and future production. Our objectives were to determine the effects of enhanced feeding preweaning and exogenous estrogen immediately postweaning on mammary gland development and the composition of the mammary parenchyma (PAR) and mammary fat pad (MFP). Thirty-six Holstein heifer calves (<1 wk old) were reared on 1 of 2 dietary treatments for 8 wk: (1) a restricted milk replacer fed at 0.45 kg/d (R; 20% crude protein, 20% fat), or (2) an enhanced milk replacer fed at 1.13 kg/d (EH; 28% crude protein, 25% fat). Upon weaning, calves from each diet (n=6) were given either a placebo or estrogen implant for 2 wk, creating 4 treatments: R, R + estrogen (R-E2), EH, and EH + estrogen (EH-E2). Calves were housed individually with ad libitum access to water. Starter feeding began at wk 5 and was balanced between treatments. Udders were evaluated by palpation and physical measurements weekly. Subsets of calves were killed at weaning (n=6 per diet) and at the conclusion of the trial (n=6 per treatment). Udders were removed, dissected, and weighed. At wk 8, EH calves had longer front and rear teats. Providing estrogen to EH calves increased the length of rear teats during wk 9 and 10. Enhanced-fed calves had 5.2-fold more trimmed mammary gland mass than R calves. Providing estrogen to EH calves further increased mammary gland weight. Masses of PAR and MFP were markedly greater for EH calves than for R calves (e.g., 7.3-fold greater PAR tissue). Estrogen increased the mass of both PAR and MFP in EH calves. Feeding a higher plane of nutrition increased total protein, DNA, and fat in the MFP and total protein and DNA in the PAR. Dual-energy x-ray absorptiometry estimates of mammary fat mass were highly correlated with biochemical analyses of fat content. From histological study, we observed that the degree of expansion of epithelium into the adjacent stromal tissue and the complexity of ductal development were minimal in R, increased in EH, and increased by estrogen in both dietary treatments. Results provide compelling evidence that preweaning nutrition and estrogen administration immediately postweaning markedly increase mammary gland development in dairy calves. Cellular and molecular mechanisms responsible for these differences are currently under study. PMID- 27372587 TI - Invited review: Opportunities for genetic improvement of metabolic diseases. AB - Metabolic disorders are disturbances to one or more of the metabolic processes in dairy cattle. Dysfunction of any of these processes is associated with the manifestation of metabolic diseases or disorders. In this review, data recording, incidences, genetic parameters, predictors, and status of genetic evaluations were examined for (1) ketosis, (2) displaced abomasum, (3) milk fever, and (4) tetany, as these are the most prevalent metabolic diseases where published genetic parameters are available. The reported incidences of clinical cases of metabolic disorders are generally low (less than 10% of cows are recorded as having a metabolic disease per herd per year or parity/lactation). Heritability estimates are also low and are typically less than 5%. Genetic correlations between metabolic traits are mainly positive, indicating that selection to improve one of these diseases is likely to have a positive effect on the others. Furthermore, there may also be opportunities to select for general disease resistance in terms of metabolic stability. Although there is inconsistency in published genetic correlation estimates between milk yield and metabolic traits, selection for milk yield may be expected to lead to a deterioration in metabolic disorders. Under-recording and difficulty in diagnosing subclinical cases are among the reasons why interest is growing in using easily measurable predictors of metabolic diseases, either recorded on-farm by using sensors and milk tests or off-farm using data collected from routine milk recording. Some countries have already initiated genetic evaluations of metabolic disease traits and currently most of these use clinical observations of disease. However, there are opportunities to use clinical diseases in addition to predictor traits and genomic information to strengthen genetic evaluations for metabolic health in the future. PMID- 27372588 TI - Characterization of the indigenous microflora in raw and pasteurized buffalo milk during storage at refrigeration temperature by high-throughput sequencing. AB - The effect of refrigeration on bacterial communities within raw and pasteurized buffalo milk was studied using high-throughput sequencing. High-quality samples of raw buffalo milk were obtained from 3 dairy farms in the Guangxi province in southern China. Five liters of each milk sample were pasteurized (72 degrees C; 15 s); and both raw and pasteurized milks were stored at refrigeration temperature (1-4 degrees C) for various times with their microbial communities characterized using the Illumina Miseq platform (Novogene, Beijing, China). Results showed that both raw and pasteurized milks contained a diverse microbial population and that the populations changed over time during storage. In raw buffalo milk, Lactococcus and Streptococcus dominated the population within the first 24h; however, when stored for up to 72h the dominant bacteria were members of the Pseudomonas and Acinetobacter genera, totaling more than 60% of the community. In pasteurized buffalo milk, the microbial population shifted from a Lactococcus-dominated community (7d), to one containing more than 84% Paenibacillus by 21d of storage. To increase the shelf-life of buffalo milk and its products, raw milk needs to be refrigerated immediately after milking and throughout transport, and should be monitored for the presence of Paenibacillus. Results from this study suggest pasteurization should be performed within 24h of raw milk collection, when the number of psychrotrophic bacteria are low; however, as Paenibacillus spores are resistant to pasteurization, additional antimicrobial treatments may be required to extend shelf-life. The findings from this study are expected to aid in improving the quality and safety of raw and pasteurized buffalo milk. PMID- 27372589 TI - Differential glucocorticoid-induced closure of the blood-milk barrier during lipopolysaccharide- and lipoteichoic acid-induced mastitis in dairy cows. AB - Bacteria invading the mammary gland can cause pathogen-dependent differences in the permeability of the blood-milk barrier leading to the differential paracellular transfer of blood and milk components. Glucocorticoids such as prednisolone (PRED) are known to increase the integrity of the blood-milk barrier and quickly restore the decreased milk quality associated with mastitis. The objective of this study was to examine the effect of intramammary PRED on the differential permeability of the blood-milk barrier during mastitis induced by lipopolysaccharide (LPS) from Escherichia coli or lipoteichoic acid (LTA) from Staphylococcus aureus. Thirty-one dairy cows, divided into 6 groups, were injected via a teat canal with LPS, LTA, LPS and PRED, LTA and PRED, saline (control), or PRED. Milk and blood samples were collected 0 to 8h after challenge and analyzed for somatic cell count, IgG, serum albumin, and lactate dehydrogenase in milk, or alpha-lactalbumin in plasma. Somatic cell count was similarly elevated in LPS- and LTA-challenged quarters and was reduced to control quarter levels only in LTA-challenged quarters with PRED administration. Lactate dehydrogenase activity was highly elevated in LPS quarters and only slightly elevated in LTA quarters, but decreased to control quarter levels with PRED administration. For serum albumin and IgG, only LPS quarters showed an elevation in concentration and PRED treatment reduced the concentration to control quarter level. We found no differences in alpha-lactalbumin concentrations in plasma in PRED-treated cows compared with cows that only received LPS or LTA. In conclusion, the pathogen-specific appearance of blood constituents in milk during mastitis demonstrates a differential activation of the blood-milk barrier that, in turn, can be manipulated by intramammary glucocorticoids. The results show that the administration of PRED during mastitis increases the blood-milk barrier integrity but has implications in reducing the transfer of IgG that specifically occurs during E. coli mastitis. In addition, it can also reduce the number of migrating immune cells dependent on the mastitis-inducing pathogen. Potential effects of PRED on the cure of naturally occurring mastitis have to be taken into consideration. PMID- 27372590 TI - Utilization of konjac glucomannan as a fat replacer in low-fat and skimmed yogurt. AB - Konjac glucomannan (KGM) has been reported to be beneficial to human health, as well as having potential functional properties as a fat replacer in dairy products. In this study, 0.5% KGM solution was added to prepare low-fat (LFKGM) and skimmed (SKKGM) yogurts, and their physicochemical properties were compared with those of full-fat yogurt control (FFC), low-fat yogurt control (LFC), and skimmed yogurt control (SKC). Properties and composition were determined and the microscopic structures of all yogurts were observed during storage at 4 degrees C for 21d. Generally, addition of KGM to yogurts had no significant effect on composition, pH, and titratable acidity at each storage day. The LFKGM and SKKGM had higher whiteness, greenness, and yellowness hues compared with those of the LFC and SKC. The proteolysis of LFKGM and SKKGM was similar to that of FFC, whereas it was lower than in LFC and SKC after 14d of storage. Addition of KGM had no positive effects on the water-holding capacity, but led to a decrease in syneresis and spontaneous whey separation in LFKGM and SKKGM compared with those of LFC and SKC. The spontaneous whey separation of LFKGM was similar to that of FFC. Presence of KGM in skimmed yogurt affected textural characteristics, while having little effect on texture of low-fat yogurt. Additionally, LFKGM and SKKGM showed stronger and more stable gel structures than those of FFC, LFC, and SKC. Overall, no substantial changes were found in the characteristics for each yogurt during storage, except for pH and gel structures. Results indicated that KGM may be a good fat replacer to develop reduced-fat yogurts with desired characteristics. PMID- 27372591 TI - Use of rumination and activity monitoring for the identification of dairy cows with health disorders: Part I. Metabolic and digestive disorders. AB - The objectives of this study were to evaluate (1) the performance of an automated health-monitoring system (AHMS) to identify cows with metabolic and digestive disorders-including displaced abomasum, ketosis, and indigestion-based on an alert system (health index score, HIS) that combines rumination time and physical activity; (2) the number of days between the first HIS alert and clinical diagnosis (CD) of the disorders by farm personnel; and (3) the daily rumination time, physical activity, and HIS patterns around CD. Holstein cattle (n=1,121; 451 nulliparous and 670 multiparous) were fitted with a neck-mounted electronic rumination and activity monitoring tag (HR Tags, SCR Dairy, Netanya, Israel) from at least -21 to 80 d in milk (DIM). Raw data collected in 2-h periods were summarized per 24 h as daily rumination and activity. A HIS (0 to 100 arbitrary units) was calculated daily for individual cows with an algorithm that used rumination and activity. A positive HIS outcome was defined as a HIS of <86 during at least 1 d from -5 to 2 d after CD. Blood concentrations of nonesterified fatty acids, beta-hydroxybutyrate, total calcium, and haptoglobin were determined in a subgroup of cows (n=459) at -11+/-3, -4+/-3, 0, 3+/-1, 7+/ 1, 14+/-1, and 28+/-1 DIM. The sensitivity of the HIS was 98% [95% confidence interval (CI): 93, 100] for displaced abomasum (n=41); 91% (95% CI: 83, 99) for ketosis (n=54); 89% (95% CI: 68, 100) for indigestion (n=9); and 93% (95% CI: 89, 98) for all metabolic and digestive disorders combined (n=104). Days (mean and 95% CI) from the first positive HIS <86 and CD were -3 (-3.7, -2.3), -1.6 (-2.3, 1.0), -0.5 (-1.5, 0.5), and -2.1 (-2.5, -1.6) for displaced abomasum, ketosis, indigestion, and all metabolic and digestive disorders, respectively. The patterns of rumination, activity, and HIS for cows flagged by the AHMS were characterized by lower levels than for cows without a health disorder and cows not flagged by the AHMS from -5 to 5 d after CD, depending on the disorder and parameter. Differences between cows without health disorders and those flagged by the AHMS for blood markers of metabolic and health status confirmed the observations of the CD and AHMS alerts. The overall sensitivity and timing of the AHMS alerts for cows with metabolic and digestive disorders indicated that AHMS that combine rumination and activity could be a useful tool for identifying cows with metabolic and digestive disorders. PMID- 27372592 TI - Changes throughout lactation in phenotypic and genetic correlations between methane emissions and milk fatty acid contents predicted from milk mid-infrared spectra. AB - The aim of this study was to estimate phenotypic and genetic correlations between methane production (Mp) and milk fatty acid contents of first-parity Walloon Holstein cows throughout lactation. Calibration equations predicting daily Mp (g/d) and milk fatty acid contents (g/100 dL of milk) were applied on milk mid infrared spectra related to Walloon milk recording. A total of 241,236 predictions of Mp and milk fatty acids were used. These data were collected between 5 and 305 d in milk in 33,555 first-parity Holstein cows from 626 herds. Pedigree data included 109,975 animals. Bivariate (i.e., Mp and a fatty acid trait) random regression test-day models were developed to estimate phenotypic and genetic parameters of Mp and milk fatty acids. Individual short-chain fatty acids (SCFA) and groups of saturated fatty acids, SCFA, and medium-chain fatty acids showed positive phenotypic and genetic correlations with Mp (from 0.10 to 0.16 and from 0.23 to 0.30 for phenotypic and genetic correlations, respectively), whereas individual long-chain fatty acids (LCFA), and groups of LCFA, monounsaturated fatty acids, and unsaturated fatty acids showed null to positive phenotypic and genetic correlations with Mp (from -0.03 to 0.13 and from -0.02 to 0.32 for phenotypic and genetic correlations, respectively). However, these correlations changed throughout lactation. First, de novo individual and group fatty acids (i.e., C4:0, C6:0, C8:0, C10:0, C12:0, C14:0, SCFA group) showed low phenotypic or genetic correlations (or both) in early lactation and higher at the end of lactation. In contrast, phenotypic and genetic correlations between Mp and C16:0, which could be de novo synthetized or derived from blood lipids, were more stable during lactation. This fatty acid is the most abundant fatty acid of the saturated fatty acid and medium-chain fatty acid groups of which correlations with Mp showed the same pattern across lactation. Phenotypic and genetic correlations between Mp and C17:0 and C18:0 were low in early lactation and increased afterward. Phenotypic and genetic correlations between Mp and C18:1 cis-9 originating from the blood lipids were negative in early lactation and increased afterward to become null from 18 wk until the end of lactation. Correlations between Mp and groups of LCFA, monounsaturated fatty acids, and unsaturated fatty acids showed a similar or intermediate pattern across lactation compared with fatty acids that compose them. Finally, these results indicate that correlations between Mp and milk fatty acids vary following lactation stage of the cow, a fact still often ignored when trying to predict Mp from milk fatty acid profile. PMID- 27372593 TI - Associations of behavior-based measurements and clinical disease in preweaned, group-housed dairy calves. AB - Producers report bovine respiratory disease and neonatal calf diarrhea as the 2 most common diseases in preweaned calves, both of which can affect calf performance and welfare. Housing calves in groups during the preweaning period has increased in popularity and has the potential to improve calf welfare, but only if producers can detect and treat disease efficiently. A health-screening tool is needed that allows producers to identify suspect animals but minimize the time spent examining healthy animals. The objective of this study was to determine if disease in preweaned, group-housed dairy calves was associated with behavioral measures of illness. This cross-sectional study included the evaluation of preweaned, group-housed calves (n=206) on 4 farms in Wisconsin, United States. Farm visits included the scoring of key behaviors (abnormal posture when lying or standing, isolation from the group, lethargy, and 2 approach tests that tested the willingness of calves to approach a stationary person) that were hypothesized to be components of sickness behavior. Following the behavior scoring, calves underwent an individual health assessment for bovine respiratory disease, neonatal calf diarrhea, and umbilical infections. Each behavior category was scored as normal (0 points) or abnormal (1 point), and then categories were summed to obtain a total behavior score for each calf. Behavior scores ranged from 0 (normal) to 5 (severely abnormal). A total behavior score of 3 or greater was considered positive for disease. The outcome of a positive or negative test on the behavior score were analyzed using PROC LOGISTIC (SAS Institute Inc., Cary, NC) and the model controlled for calf age and farm. Bovine respiratory disease was significantly associated with a behavior score of 3 or greater. The use of a behavior score shows promise as a screening tool for disease in preweaned calves. PMID- 27372594 TI - Plasma exosome profiles from dairy cows with divergent fertility phenotypes. AB - Cell-to-cell communication in physiological and pathological conditions may be influenced by neighboring cells, distant tissues, or local environmental factors. Exosomes are specific subsets of extracellular vesicles that internalize and deliver their content to near and distant sites. Exosomes may play a role in the maternal-embryo crosstalk vital for the recognition and maintenance of a pregnancy; however, their role in dairy cow reproduction has not been established. This study aimed to characterize the exosome profile in the plasma of 2 strains of dairy cow with divergent fertility phenotypes. Plasma was obtained and characterized on the basis of genetic ancestry as fertile (FERT; <23% North American genetics, New Zealand Holstein-Friesian strain, n=8) or subfertile (SUBFERT; >92% North American genetics, North American Holstein Friesian strain, n=8). Exosomes were isolated by differential and buoyant density centrifugation and characterized by size distribution (nanoparticle tracking analysis, NanoSight NS500, NanoSight Ltd., Amesbury, UK), the presence of CD63 (Western blot), and their morphology (electron microscopy). The total number of exosomes was determined by quantifying the immunoreactive CD63 (ExoELISA kit, System Biosciences), and the protein content established by mass spectrometry. Enriched exosome fractions were identified as cup-shape vesicles with diameters around 100 nm and positive for the CD63 marker. The concentration of exosomes was 50% greater in FERT cows. Mass spectrometry identified 104 and 117 proteins in FERT and SUBFERT cows, of which 23 and 36 were unique, respectively. Gene ontology analysis revealed enrichment for proteins involved in immunomodulatory processes and cell-to-cell communication. Although the role of exosomes in dairy cow reproduction remains to be elucidated, their quantification and content in models with divergent fertility phenotypes could provide novel information to support both physiological and genetic approaches to improving dairy cow fertility. PMID- 27372595 TI - Effects of lactic acid bacteria silage inoculation on methane emission and productivity of Holstein Friesian dairy cattle. AB - Inoculants of lactic acid bacteria (LAB) are used to improve silage quality and prevent spoilage via increased production of lactic acid and other organic acids and a rapid decline in silage pH. The addition of LAB inoculants to silage has been associated with increases in silage digestibility, dry matter intake (DMI), and milk yield. Given the potential change in silage and rumen fermentation conditions accompanying these silage additives, the aim of this study was to investigate the effect of LAB silage inoculants on DMI, digestibility, milk yield, milk composition, and methane (CH4) production from dairy cows in vivo. Eight mid-lactation Holstein-Friesian dairy cows were grouped into 2 blocks of 4 cows (multiparous and primiparous) and used in a 4*4 double Latin square design with 21-d periods. Methane emissions were measured by indirect calorimetry. Treatments were grass silage (mainly ryegrass) with no inoculant (GS), with a long-term inoculant (applied at harvest; GS+L), with a short-term inoculant (applied 16h before feeding; GS+S), or with both long and short-term inoculants (GS+L+S). All diets consisted of grass silage and concentrate (75:25 on a dry matter basis). The long-term inoculant consisted of a 10:20:70 mixture of Lactobacillus plantarum, Lactococcus lactis, and Lactobacillus buchneri, and the short-term inoculant was a preparation of Lc. lactis. Dry matter intake was not affected by long-term or short-term silage inoculation, nor was dietary neutral detergent fiber or fat digestibility, or N or energy balance. Milk composition (except milk urea) and fat and protein-corrected milk yield were not affected by long- or short-term silage inoculation, nor was milk microbial count. However, milk yield tended to be greater with long-term silage inoculation. Methane expressed in units of grams per day, grams per kilogram of DMI, grams per kilogram of milk, or grams per kilogram of fat and protein-corrected milk yield was not affected by long- or short-term silage inoculation. However, CH4 expressed in units of kilojoules per kilogram of metabolic body weight per day tended to be greater with long-term silage inoculation. Results of this study indicate minimal responses in animal performance to both long- and short-term inoculation of grass silage with LAB. Strain and dose differences as well as different basal silages and ensiling conditions are likely responsible for the lack of significant effects observed here, although positive effects have been observed in other studies. PMID- 27372596 TI - Platelet-to-White Blood Cell Ratio: A Prognostic Predictor for 90-Day Outcomes in Ischemic Stroke Patients with Intravenous Thrombolysis. AB - BACKGROUND: This study is aimed to investigate the relationship between platelet to-white blood cell ratio (PWR) and 90-day outcomes in acute stroke patients with intravenous thrombolysis (IVT). MATERIALS AND METHODS: A retrospective analysis was performed on 168 patients receiving IVT for acute ischemic stroke. Complete blood count evaluation was conducted at admission before IVT. A modified Rankin Scale (mRS) score of 3-6 at 90 days was considered an unfavorable outcome. RESULTS: A total of 168 patients were included from 2013 to 2015. The mean age of the sample was 64.6 (+/-12.3) years, and 23.2% were women. The median baseline National Institutes of Health Stroke Scale score was 7.5 (interquartile range [IQR] 8.0) and the 90-day mRS score was 2 (IQR 2). In our multivariate logistic regression model, a PWR greater than 23.52 (odds ratio .454, 95% confidence interval: .212-.973, P < .050) was a predictor of 90-day outcomes. In addition, there was a significant difference in the PWR values of patients between favorable outcome and unfavorable outcome in the large-artery atherosclerosis subtype (28.241 +/- 11.581 and 21.899 +/- 9.107, respectively; P = .005). CONCLUSIONS: The PWR at admission predicts 90-day outcomes in ischemic stroke patients with IVT. With the easy and routine use of hemogram analysis, the PWR should be investigated in further prospective randomized controlled trials of acute stroke. PMID- 27372597 TI - Pediatric Sleep Apnea Syndrome: An Update. AB - Obstructive sleep apnea syndrome (OSAS) may be central neurologic (<5%) or obstructive (>95%) in origin and is a relatively prevalent condition in children. It affects 1%-5% of children aged 2-8 years and is caused by a variety of different pathophysiologic abnormalities. Cardiovascular, metabolic, and neurocognitive comorbidities can occur in both children and adults when left untreated. It also can cause severe behavioral problems in children. The American Academy of Pediatrics recommends that all children be screened with an appropriate history and physical examination for symptoms and signs suggestive of OSAS. The diagnosis is primarily made clinically and confirmed by polysomnographic findings. Treatment depends on the child's age, underlying medical problems, polysomnography findings, and whether or not there is upper airway obstruction usually secondary to enlarged adenoids and/or tonsils, allergic and nonallergic rhinitis, acute and chronic sinusitis, and other upper airway pathology. If enlarged adenoid or tonsils or both conditions exist, an adenoidectomy, tonsillectomy, or adenotonsillectomy remains the treatment of choice. Pharmacotherapy of OSAS has shown some effect in children with mild symptoms. This paper reviews the prevalence, pathophysiology, clinical presentation, diagnosis, and treatment of OSAS. PMID- 27372598 TI - Internet and food allergy: What patients are seeking and what they do with the information. PMID- 27372599 TI - Burden of Obesity on Pediatric Inpatients with Acute Asthma Exacerbation in the United States. AB - BACKGROUND: Obesity and asthma are common health problems in the United States. OBJECTIVE: The objective of this study was to evaluate the clinical and economic burdens of obesity on hospitalized children with acute asthma exacerbation in 2012. METHODS: Hospital discharge records of patients aged 2 to 18 years with a diagnosis of asthma were obtained from the 2012 Kids' Inpatient Database, wherein the data were compiled by the Agency for Healthcare Research and Quality. The discharge records were weighted to estimate the number of hospitalizations because of asthma exacerbations in the United States. To classify whether the patient was obese or not, we used the International Classification of Diseases, Ninth Revision, Clinical Modification code 278.0x. We compared the odds of using noninvasive or invasive mechanical ventilation, mean total charges for inpatient service, and length of hospital stay between obese and nonobese patients. RESULTS: A total of 74,338 patient discharges were extracted. Of these, 3,494 discharges were excluded because of chronic medical conditions. Using discharge weight variables, we estimated a total of 100,157 hospitalizations with asthma exacerbations among children aged between 2 and 18 years in 2012. Obesity was significantly associated with higher odds of using mechanical ventilation (odds ratio 1.59, 95% CI 1.28-1.99), higher mean total hospital charges (adjusted difference: $1588, 95% CI $802-$2529), and longer mean length of hospital stay (0.24 days, 95% CI 0.17-0.32 days) compared with nonobesity. CONCLUSIONS: These findings suggest that obesity is a significant risk factor of severe asthma exacerbation that requires mechanical ventilation, and obesity is an economically complicating factor. PMID- 27372600 TI - No association between atopic outcomes and type of pertussis vaccine given in children born on the Isle of Wight 2001-2002. PMID- 27372601 TI - H1-Antihistamine Premedication in NSAID-Associated Urticaria. AB - BACKGROUND: Therapeutic options for pain management are restricted in patients with nonsteroidal anti-inflammatory drug (NSAID)-induced or NSAID-exacerbated urticaria because strong cyclooxygenase (COX)-I inhibiting NSAID cannot be used. Alternative NSAID such as weak COX-I inhibitors or selective COX-II inhibitors are sometimes not sufficiently effective or have potentially troublesome adverse effects. OBJECTIVE: To date, prophylactic premedication with H1-antihistamines is rarely practiced in patients concurrently suffering from recurrent pain and NSAID associated urticaria. Our data analysis aims to clarify whether prophylactic premedication before the intake of NSAID is effective, safe, and practicable. METHODS: Data of 21 patients with NSAID-induced or NSAID-exacerbated urticaria who underwent single dose NSAID provocation 30 minutes after premedication with 5 mg desloratadine were retrospectively evaluated. RESULTS: After H1-antihistamine premedication, 17 patients tolerated 16 single dose provocation tests with strong COX-I inhibitors and 2 tests with weak COX-I inhibitors. Despite H1-antihistamine premedication, 2 patients developed acute urticaria after intake of 400 mg ibuprofen. Another 2 patients with acute urticaria after intake of 800 mg ibuprofen tolerated 400 mg ibuprofen and 1000 mg paracetamol, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In the majority of patients with NSAID induced or NSAID-exacerbated urticaria concurrently suffering from intermittent pain, a premedication regimen with 5 mg desloratadine 30 minutes before intake of a strong COX-I inhibitor seems to be effective, safe, and practicable. PMID- 27372602 TI - GPCRs in immunity: Atypical receptors and novel concepts. PMID- 27372603 TI - 3,3'-Diindolylmethane induces anti-human gastric cancer cells by the miR-30e-ATG5 modulating autophagy. AB - 3,3'-Diindolylmethane (DIM), a class of relatively non-toxic indole derivatives from cruciferous vegetables, has been reported as a promising anticancer phytochemical, but the underlying molecular mechanism is not completely elucidated. In the present study we report a novel regulation of autophagy by DIM in human gastric cancer cells. We found that DIM dose-dependently inhibited the growth of gastric cancer cells in vitro and in vivo. Moreover, ATG5 and LC3 were activated by DIM in gastric cancer cells. Furthermore, miR-30e was down-regulated by DIM and miR-30e targeted the 3'-UTR of ATG5 to inhibit its translation. Overall, these results suggest that DIM may through the miR-30e-ATG5 modulating autophagy inhibit the proliferation of gastric cancer cells. PMID- 27372604 TI - Outcomes following acute hospitalised myocardial infarction in France: An insurance claims database analysis. AB - BACKGROUND: Mortality and complications of acute myocardial infarction (AMI) in France have declined over the last twenty years, but still remain high. Practice guidelines recommend secondary prevention measures to reduce these. Insurance claims databases can be used to assess the management of post MI and other cardiovascular outcomes in everyday practice. METHODS: A cohort study was performed in a 1/97 representative sample of the French nationwide claims and hospitalisation database (EGB database). All adults with a documented hospitalisation for MI between 2007 and 2011 were included, and followed for three years. Data was extracted on demographics, the index admission, reimbursed medication, comorbidities, post-MI events and death. RESULTS: During the study period, 1977 individuals hospitalised for an MI were identified, with a mean (+/ SD) age of 63.8 (+/-14.3) years, 65.8% were men, 82.4% had hypertension and 37.6% hypercholesterolaemia. The mean duration of hospitalisation was seven days and 8.3% of patients died during hospitalisation. After discharge, the majority of patients received secondary prevention with statins (92.2%), anti-platelet drugs (95.6%), beta-blockers (86.0%) and angiotensin converting enzyme inhibitors (71.4%). After three years of follow-up post-discharge, cumulative mortality was 20.5% [18.4%;22.5%] and the cumulative incidence of reinfarction and stroke/TIA were 4.7% [95% CI: 3.7%;5.7%] and 4.1% [3.1%;5.0%], respectively. CONCLUSIONS: Despite high use of secondary prevention at discharge, mortality and incidence of serious cardiovascular events following MI remain high. This underscores the need to improve secondary prevention. PMID- 27372605 TI - Alexithymia affects the time from symptom onset to calling the emergency system in STEMI patients referred for primary PCI. AB - BACKGROUND: STEMI programs have been found to reduce the time to reperfusion but do not address the time delay caused by patients. In this study we sought to assess whether and to what extent alexithymia, defined as the inability to recognize and describe somatic feelings appropriately, impacts on this delay. METHODS: Ninety-five STEMI patients referred by the Emergency Medical System (EMS) to our hospital for primary percutaneous coronary intervention were studied. The time from symptom onset to the EMS call (time to call) as well as the time from the EMS call to the first intervention that restored patency of the culprit vessel (system delay) and the total ischemic time was calculated in patients categorized into two groups according to the Toronto Alexithymia scale (TAS-20): patients with higher alexithymia scores (>=61), and patients with lower scores of alexithymia (<61). RESULTS: According to the TAS-20, we identified 27 patients as being alexithymic and 68 patients as not. The time to call and the total ischemic time were longer in alexithymic compared to non alexithymic patients (respectively, 159min vs 35min, and 258.5 vs 139 , p=0.001), while the system delay was similar in both groups. CONCLUSIONS: Alexithymia is one trait of the patient personality which appears to have negative implications in the setting of a STEMI network by interfering with prompt seeking of care. This information could help in guiding novel strategies to motivate patients to call EMS quickly and further shorten the total ischemic time. PMID- 27372606 TI - Early left atrial tissue features in patients with chronic mitral regurgitation and sinus rhythm: Alterations of not remodeled left atria. AB - OBJECTIVE: Left atrial (LA) enlargement, a compensatory mechanism in chronic mitral regurgitation (MR) increasing the risk of atrial fibrillation (AF) and predictive of cardiac events, involves structural alterations. We characterized LA features in patients in sinus rhythm with severe degree of MR, similar degrees of left ventricular remodeling but divergent LA size. METHODS: Among a consecutive series of 163 patients in stable sinus rhythm undergoing isolated mitral valve surgery for severe non-rheumatic MR, two groups were arbitrarily selected according to their LA size (antero-posterior): NRLA group (non-remodeled LA) included 8 patients with LA<=40mm, RLA group (remodeled LA) included 8 patients with LA>55mm. LA biopsies were processed for paraffin inclusion and sectioning. Fibrosis, cardiomyocytes morphology, capillaries density, cytochrome c and F-actin expression were evaluated by microscopy. RESULTS: Histology and immunohistochemistry demonstrated alteration of moderate entity: higher amounts of endomysial fibrosis (not of collagen type III) and of hypertrophic cardiomyocytes in RLA than in NRLA. Confocal microscopy displayed focally disorganized F-actin and no nuclear fragmentation in both groups, but more intra cytoplasm cytochrome c in RLA vs. NRLA, possibly indicative of more successful escape to apoptosis by NRLA cardiomyocytes. CONCLUSIONS: Our study shows the presence of early cellular and interstitial alterations in LA tissue in patients with chronic MR and sinus rhythm. These features were analogous to those of patients with AF, and suggest that macroscopic remodeling LA in the settings of MR is preceded by structural changes, paving the way to further investigation on the preventive role of early mitral valve repair. PMID- 27372607 TI - Echocardiographic prevalence of rheumatic heart disease in Brazilian schoolchildren: Data from the PROVAR study. AB - BACKGROUND: Accurate estimates of Rheumatic Heart Disease (RHD) burden are needed to justify improved integration of RHD prevention and screening into the public health systems, but data from Latin America are still sparse. OBJECTIVE: To determine the prevalence of RHD among socioeconomically disadvantaged youth (5 18years) in Brazil and examine risk factors for the disease. METHODS: The PROVAR program utilizes non-expert screeners, telemedicine, and handheld and standard portable echocardiography to conduct echocardiographic screening in socioeconomically disadvantaged schools in Minas Gerais, Brazil. Cardiologists in the US and Brazil provide expert interpretation according to the 2012 World Heart Federation Guidelines. Here we report prevalence data from the first 14months of screening, and examine risk factors for RHD. RESULTS: 5996 students were screened across 21 schools. Median age was 11.9 [9.0/15.0] years, 59% females. RHD prevalence was 42/1000 (n=251): 37/1000 borderline (n=221) and 5/1000 definite (n=30). Pathologic mitral regurgitation was observed in 203 (80.9%), pathologic aortic regurgitation in 38 (15.1%), and mixed mitral/aortic valve disease in 10 (4.0%) children. Older children had higher prevalence (50/1000 vs. 28/1000, p<0.001), but no difference was observed between northern (lower resourced) and central areas (34/1000 vs. 44/1000, p=0.31). Females had higher prevalence (48/1000 vs. 35/1000, p=0.016). Age (OR=1.15, 95% CI:1.10-1.21, p<0.001) was the only variable independently associated with RHD findings. CONCLUSIONS: RHD continues to be an important and under recognized condition among socioeconomically disadvantaged Brazilian schoolchildren. Our data adds to the compelling case for renewed investment in RHD prevention and early detection in Latin America. PMID- 27372608 TI - ATPase activity measurement of DNA replicative helicase from Bacillus stearothermophilus by malachite green method. AB - The DnaB helicase from Bacillus stearothermophilus (DnaBBst) was a model protein for studying the bacterial DNA replication. In this work, a non-radioactive method for measuring ATPase activity of DnaBBst helicase was described. The working parameters and conditions were optimized. Furthermore, this method was applied to investigate effects of DnaG primase, ssDNA and helicase loader protein (DnaI) on ATPase activity of DnaBBst. Our results showed this method was sensitive and efficient. Moreover, it is suitable for the investigation of functional interaction between DnaB and related factors. PMID- 27372609 TI - Characterization of protein expression levels with label-free detected reverse phase protein arrays. AB - In reverse-phase protein arrays (RPPA), one immobilizes complex samples (e.g., cellular lysate, tissue lysate or serum etc.) on solid supports and performs parallel reactions of antibodies with immobilized protein targets from the complex samples. In this work, we describe a label-free detection of RPPA that enables quantification of RPPA data and thus facilitates comparison of studies performed on different samples and on different solid supports. We applied this detection platform to characterization of phosphoserine aminotransferase (PSAT) expression levels in Acanthamoeba lysates treated with artemether and the results were confirmed by Western blot studies. PMID- 27372610 TI - Hippocampal Area CA2: An Overlooked but Promising Therapeutic Target. AB - While the hippocampus has long been recognized as a brain structure specialized in mapping 'space' in rodents, human studies and now recent data from rodents have shown that its function extends well beyond spatial coding. Recently, an overlooked area of the hippocampus, CA2, has emerged as a critical region for social memory. This area is also uniquely altered during several pathologies such as schizophrenia and age-related dementia. Because of its singular connectivity, we propose that area CA2 resides at the interface between emotional brain activity and higher cognitive function. Furthermore, because of the unique expression of multiple neuromodulator receptors in area CA2, we posit that this region may represent a fruitful therapeutic target for diseases where social dysfunction occurs. PMID- 27372611 TI - Association between Vitamin D and arterial stiffness. PMID- 27372612 TI - Arterial stiffness parameters associated with vitamin D deficiency and supplementation in patients with normal cardiac functions. AB - OBJECTIVE: Arterial stiffness parameters including pulse wave velocity (PWV) and augmentation index (AIx) are associated with increased risk of cardiovascular disease. A close relationship has been demonstrated between vitamin D deficiency and cardiovascular disease. The aim of the present study was to investigate effects of vitamin D deficiency and supplementation on arterial stiffness parameters in patients with normal cardiac functions. METHODS: Study population consisted of 45 patients with vitamin D deficiency and normal cardiac functions. Median age (interquartile range) was 45.0 (12.00) years, and 33 patients were female. Patients were treated with oral administration of vitamin D3. Arterial stiffness parameters were evaluated using Mobil-O-Graph arteriograph system, which detected signals from the brachial artery before and after treatment. RESULTS: Vitamin D levels significantly increased after treatment (9.0 [6.00] nmol/L vs 29.0 [11.50] nmol/L, p<0.001). No significant difference was observed among conventional echocardiographic parameters before or after treatment. Post treatment PVW and AIx were significantly lower than baseline measurements (6.8 [1.55] m/s vs 6.4 [1.30] m/s, p<0.001 and 23.0 [22.00]% vs 31.0 [14.50]%, p<0.001, respectively). Baseline vitamin D levels significantly correlated with PWV (r=-0.352, p=0.018). Post-treatment vitamin D levels also significantly correlated with post-treatment PWV (r=-0.442, p=0.002) and AIx (r=-0.419, p=0.004). Multivariate linear regression analysis revealed no independent predictor of baseline log-transformed PWV. CONCLUSION: Vitamin D supplementation has beneficial effects on arterial stiffness. Arterial stiffness parameters may aid in the assessment of cardiovascular risk in patients with vitamin D deficiency. PMID- 27372614 TI - [Effect of pulmonary endarterectomy on six-minute walking test and echocardiography in the early stage]. AB - OBJECTIVE: Pre- and postoperative changes in echocardiographic parameters and results of 6-minute walking test (6-MWT) were investigated in the present study. METHODS: Seventy-six patients (32 males, 44 females; mean age 45.9+/-15.1 years) were included. Before and after surgery, 6-MWT and echocardiography were performed. Changes in postoperative parameters were compared to basal walking test and other basal parameters. RESULTS: Distance covered in 6-MWT significantly increased after surgery (p<0.001). Significant decrease in right ventricular diameter and pressure, and significant increase in left ventricular diameter were also observed. While changes in ejection fraction (EF) were not significant, significant reduction in systolic pulmonary artery pressure (sPAP) and tricuspid regurgitation were observed. No statistically significant correlation was observed between baseline 6-MWT results and echocardiographic parameters. CONCLUSION: The present study was the first to investigate the correlation between baseline 6-MWT results and right ventricular echocardiographic parameters. Myocardial performance index (MPI) and TAPSE were important parameters in follow-up after pulmonary endarterectomy. Improvement in quality of life parameters was also important. PMID- 27372613 TI - Relation of elastic properties of pulmonary artery with left ventricular abnormalities and aortic stiffness in patients with moderate to severe obstructive sleep apnea: A cross-sectional echocardiographic study. AB - OBJECTIVE: In this study, the associations between pulmonary artery stiffness (PAS) and aortic stiffness, left ventricular diastolic parameters, and left ventricular mass (LVM) index in moderate to severe obstructive sleep apnea syndrome (OSAS) patients without coexisting disorders were investigated. METHODS: A total of 66 non-diabetic, non-hypertensive, and non-smoking volunteers were enrolled. Participants were categorized by apnea-hypopnea index (AHI; event/hour). The control group was defined as no OSAS: AHI<5 (n=35), and OSAS group had moderate to severe OSAS: AHI>15 (n=31).Echocardiographic and biochemical tests, including measurement of C-reactive protein (CRP), were performed. PAS (kHz/s) was calculated by dividing the maximal frequency shift of the pulmonary flow by the acceleration time. RESULTS: PAS (kHz/s), obtained by echocardiography, was statistically significantly higher in the OSAS group than the control group (28+/-5 vs 18+/-4, p<0.001), and was positively correlated with AHI, CRP, aortic stiffness index, E/E', and LVM index (p=0.034, p=0.039, p<0.001, p=0.040, and p<0.001, respectively), and negatively correlated with aortic strain (AS), aortic distensibility (AD), E/A, E'/A', and E' (p<0.001). Regression analyses indicated that CRP and PAS are independent predictors of aortic stiffness (p<0.05). E/A and LVM index were independent predictors of PAS (p=0.002 and p=0.001, respectively). CONCLUSION: Increased PAS is associated with aortic stiffness, left ventricular diastolic function, and increased LVM index. PAS may be a more effective indicator of aortic stiffness in OSAS patients than CRP. PMID- 27372615 TI - Evaluation of heart rate variability in patients with coronary artery ectasia and coronary artery disease. AB - OBJECTIVE: The present study compared heart rate variability (HRV) parameters in patients with coronary artery ectasia (CAE) and coronary artery disease (CAD). METHODS: The study population consisted of 60 consecutive patients with CAE (14 women; mean age 51.63+/-7.44 years), 60 consecutive patients with CA (15 women; mean age 53.67+/-9.31 years), and 59 healthy individuals (13 women; mean age 52.85+/-8.19 years). Electrocardiograms, 24-hour Holter analyses, and routine biochemical tests were performed, and clinical characteristics were evaluated. Coronary angiography images were analyzed. Time-domain HRV parameters, including the standard deviation (SD) of normal-to-normal intervals (SDNN) and the root mean square of difference in successive normal-to-normal intervals (RMSSD) were evaluated, as were frequency-domain HRV parameters including low-frequency (LF), very low-frequency (VLF), high-frequency (HF), the proportion derived by dividing low- and high-frequency (LF/HF), and total power (TP). RESULTS: SDNN was lower in both the CAE and CAD groups, compared to the healthy group (140.85+/-44.21, 96.51+/-31.28, and 181.05+/-48.67, respectively). A significant difference in RMSSD values among the groups was determined (p=0.004). Significantly decreased VLF and HF values were found in the CAE group, compared with the healthy group (VLF p<0.001; HF, p=0.007). TP, VLF, and HF values were significantly lower (p<0.001, p<0.001, and p<0.001, respectively), but LF and LF/HF values were significantly higher (p<0.001 for both) in the CAD group than in the healthy group. TP values were significantly higher (p<0.001), and LF and LF/HF values were lower in the CAE group, compared with the CAD group (p<0.001 for both). CONCLUSION: A decrease in vagal modulation or an increase in sympathetic activity of cardiac function, assessed by HRV analysis, is worse in patients with CAD than in patients with CAE. PMID- 27372616 TI - A rare pathology: Levoatriocardinal vein. AB - OBJECTIVE: Levoatriocardinal vein (LACV) is a rare cardiac pathology that represents a connection between the pulmonary venous and cardinal systems. The aim of the present study was to discuss morphological and clinical characteristics, as well as diagnostic methods, of experience with LACV. METHODS: Records of 11 patients (4 male, 7 female; mean age 79+/-1.83 days; range 1-390 days) diagnosed with LACV between 2010 and 2014 were retrospectively reviewed. Presence of LACV was confirmed with echocardiography. The primary obstructive lesion associated with cardiac defects and the integrity of the interatrial septum was identified in each patient with left-sided obstruction. RESULTS: Mean weight was 4.4+/-0.4 kg (range: 2-8). Age at presentation was under 1 year in 82% of patients. Nine patients had left-sided obstruction, and 2 had normal intracardiac anatomy and pulmonary venous return. In patients with left-sided obstruction, LACV was initially demonstrated with echocardiographic evaluation, performed in apical 4-chamber, high parasternal, and subcostal views. Atrial septum was restrictive or intact in patients with left-sided obstructions. LACV originated directly from the left atrium in all patients. CONCLUSION: Levoatriocardinal vein is an extremely rare cardiac pathology, presenting almost exclusively in patients with left-sided obstructive lesions. In patients with left-sided obstructions, LACV must be kept in mind. It may also present in patients with normal intracardiac anatomy and pulmonary venous return. PMID- 27372617 TI - Status of Turkey's top publications in cardiovascular medicine, revisited after 4 years. AB - OBJECTIVE: The aim of the present assessment was to identify "genuine" medical papers generated by Turkey's institutions that have contributed most to cardiovascular medicine. METHODS: Based on Web of Science data, 160 papers were identified as having received 40 or more citations as of late July 2015. Papers with more than minor contribution from international authors were excluded. RESULTS: A total of 127 primary authors generated 160 papers, each receiving >=40 (95% confidence interval 40-165) citations. These papers corresponded in quality to the global top 15% and were estimated to represent a global share of 3 per mille. Half were published between 2001 and 2006, with a median exposure period of 10.4 years. An estimated 9 of these papers have been produced in Turkey annually since around the turn of the century. Cardiology generated 120 articles, cardiovascular surgery 35, and pediatric cardiology 6. These papers originated from only 28 medical faculties, Gulhane Military Medical Academy (GATA), and 9 hospitals that are not academically affiliated. A majority of related Turkish institutions have shown disappointing performance. CONCLUSION: The present assessment demonstrates that the unsatisfactory performance of Turkey's contribution to cardiovascular medicine has further regressed, if slightly, particularly since 2006. Unless a wide-scale concerted effort is made to build an environment focused on research with a potential to contribute, Turkey's gap in the field is likely to widen. PMID- 27372618 TI - Tricuspid valve chordal rupture after a motorbike accident. AB - Cardiac valve injury, a condition that can follow blunt thoracic trauma, has a wide range of clinical presentations, depending on the structures involved. Post traumatic tricuspid regurgitation is relatively rare, caused by increase in intrathoracic pressure when the tricuspid valve leaflets close, leading to rupture of the chordae tendineae. A case of severe tricuspid regurgitation due to chordal rupture presenting with atrial flutter following a motorbike accident is described in the present report. PMID- 27372619 TI - Aortopulmonary window in adulthood: Surviving at 22 years without intervention or pulmonary vascular disease. AB - Aortopulmonary window is a rare anomaly, a communication between the ascending aorta and the main pulmonary artery. Prognosis in the absence of correction is poor, with mortality of around 40% in the first year of life. A case of aortopulmonary window without pulmonary vascular disease in adulthood is described in the present report. PMID- 27372620 TI - Resolution of left ventricular thrombus with apixaban in a patient with hypertrophic cardiomyopathy. AB - Anticoagulation with warfarin is the main treatment of intracardiac thrombus. While novel oral anticoagulants (NOACs) have been approved by the US Food and Drug Administration (FDA) for stroke prevention in patients with nonvalvular atrial fibrillation (AF), they are not indicated for resolution of intracardiac thrombus. The case of a 60-year-old woman with left ventricular (LV) thrombus secondary to hypertrophic cardiomyopathy and AF is described in the present report. Indications for oral anticoagulation were AF and LV thrombus. Thrombus was dissolved after 1 month of apixaban treatment. To the best of our knowledge, this is the first report that describes the resolution of LV thrombus with apixaban treatment in a patient with hypertrophic cardiomyopathy. PMID- 27372621 TI - [Long-term survival in a case of unoperated single ventricle]. AB - Single ventricle is a rare congenital heart disease, typically diagnosed with dyspnea and cyanosis. The number of patients who reach adulthood without having undergone surgical treatment is limited due to poor prognosis. While some reports describe patients who have reached the 2nd and 3rd decades of life, it is very interesting that the case of the patient who has lived the longest with unoperated single ventricle is reported in Turkey. PMID- 27372622 TI - DOCK8 deficiency in a boy who presented with a giant aortic aneurysm between aortic root and iliac bifurcation. AB - Dedicator of cytokinesis 8 protein (DOCK8) deficiency is an autosomal recessive, inherited form of hyper-immunoglobulin E (hyper-IgE) syndrome, characterized by persistent cutaneous viral infections, elevated IgE, eosinophilia, and allergic manifestations. The case of a 10-year-old boy who presented with giant aortic aneurysm between the aortic root and iliac bifurcation is described in the present report. Aortic aneurysm of this size has not yet been reported. PMID- 27372623 TI - "Not-so-identical" twins with trisomy 21 and perimembranous ventricular septal defects. AB - While trisomy 21 is a common genetic disorder in singletons, the incidence among identical twins is very rare, occurring in approximately 1-2 per 1000 twin gestations. Trisomy 21 is associated with high incidence of congenital heart defects, and commonly occurs with ventricular septal defects (VSDs). Physiologic burden of VSDs depends on prevalence of anatomic and other circulatory factors. A case of identical twins with trisomy 21 and large VSDs is described in the present report. Though genetically identical, phenotypes varied significantly. One twin was managed medically, while the other developed more significant heart failure, requiring operative repair. PMID- 27372625 TI - Case images: Percutaneous closure of transseptal puncture-related non-coronary cusp perforation with Amplatzer Duct Occluder II. PMID- 27372624 TI - Case images: Cardiac hydatid cyst presenting as double-chambered left ventricle. PMID- 27372626 TI - Case images: Ortner's Syndrome caused by ductus arteriosus aneurysm. PMID- 27372627 TI - Case images: Mediastinal mass compressing the right atrium. PMID- 27372628 TI - Case images: Aortic stent implantation in patient with subtotal aortic interruption. PMID- 27372629 TI - Relationship between epicardial fat thickness and hypertension. PMID- 27372630 TI - Authors' reply. PMID- 27372631 TI - Can utilization of therapeutic hypothermia with cold saline infusion and external cooling be increased in Turkey? PMID- 27372632 TI - Authors' reply. PMID- 27372633 TI - Facile synthesis of flower-like platinum nanostructures as an efficient electrocatalyst for methanol electro-oxidation. AB - This paper presents a facile approach for the synthesis of a novel Pt/graphene nickel foam (Pt/GNF) electrode composed of flower-like Pt nanoparticles (NPs) and 3D graphene. The fabrication process involved the chemical vapor deposition of graphene onto Ni foam as a substrate and the subsequent growth of Pt NPs via a galvanic replacement reaction without using any seed and organic solvent. The surface morphology and composition of the prepared materials were characterized. Meanwhile, cyclic voltammetry and electrochemical impedance spectroscopy were employed to confirm their typical electrochemical characteristics. The as prepared nanocomposites displayed enhanced catalytic activity and kinetics toward methanol electro-oxidation. Such an excellent performance can be ascribed to the high dispersion of flower-like Pt NPs and to the exposure of more sites provided by the flower-like structure. The improved stability, decreased charge transfer resistance, and enhanced reaction rate of the nanocomposites promise new opportunities for the development of direct methanol fuel cells. PMID- 27372634 TI - Formation and stabilization of nanoemulsions using biosurfactants: Rhamnolipids. AB - Nanoemulsions are used in the food, cosmetics, personal care and pharmaceutical industries to provide desirable optical, textural, stability, and delivery characteristics. In many industrial applications, it is desirable to formulate nanoemulsions using natural ingredients so as to develop label-friendly products. Rhamnolipids are biosurfactants isolated from certain microorganisms using fermentation processes. They are glycolipids that have a polar head consisting of rhamnose units and a non-polar tail consisting of a hydrocarbon chain. In this study, the interfacial characteristics of this natural surfactant at medium chain triglyceride (MCT) oil-water interfaces were characterized, and its ability to form nanoemulsions was compared to that of another natural surfactant (quillaja saponins). The influence of rhamnolipid concentration, homogenization pressure, and oil type on the mean droplet diameter of emulsions produced by microfluidization was determined. Rhamnolipids were highly effective at forming small droplets (d32<0.15MUm) at low surfactant-to-oil ratios (SOR<1:10) for MCT oil. Rhamnolipids could also be used to form small droplets using long chain triglyceride oils, such as corn and fish oil. Rhamnolipid-coated droplets were stable to aggregation over a range of pH values (5-9), salt concentrations (<100mM NaCl) and temperatures (20-90 degrees C). However, droplet aggregation was observed at highly acidic (pH 2-4) and high ionic strength (200-500mM NaCl) conditions. These effects were attributed to a reduction in electrostatic repulsion at low pH and high salt levels. Rhamnolipid-coated droplets had a high negative charge at neutral pH that decreased in magnitude with decreasing pH. These results indicate that rhamnolipids are effective natural surfactants that may be able to replace synthetic surfactants in certain commercial applications. PMID- 27372635 TI - Sensorimotor therapy and time to full oral feeding in <33weeks infants. AB - BACKGROUND: Previous research has shown that oral stimulation improves feeding skills in preterm infants. However, it remains unclear whether other sensorimotor therapies have similar effect. OBJECTIVE: To investigate the effect of sensorimotor therapy on the time to reach full oral feeding (FOF) in infants <33weeks. METHODS: Retrospective review compared two time periods between 2009 and 2014, before (PRE TX) and after (POST TX) initiation of sensorimotor therapy to infants <33weeks. Type and number of sensorimotor therapy, time to FOF and length of stay (LOS) were collected. Statistical analysis used SPSS 22 for descriptive, non-parametric testing, chi-square and multivariate linear regression computation. RESULTS: Of 245 records, 137 were excluded due to death, record unavailability/incompleteness or transfer. The remaining 55 in PRE TX and 53 in POST TX infants differed by small for gestational age (SGA) (36.4% vs. 28.3%, p=0.02); sepsis (81.8% vs. 54.7%, p=0.002); patent ductus arteriosus (PDA) (5.5% vs. 22.6%, p=0.01) and bradycardia (47.3% vs. 83%, p<0.0001). Infants in (POST TX) achieved FOF in 6.3+/-4.3days vs. 8.8+/-6.6days in (PRE TX) (p=0.02); their LOS was 56.8+/-26.4 vs. 52.2+/-25.1 (p=0.36). Predictors of days to FOF were any number of therapy sessions (beta=-4.31; 95% CI: -6.47:-2.15), LOS (beta=0.05; 95% CI: 0.004:0.09), PDA (beta=3.23; 95% CI: 0.27:6.19) and bradycardia (beta=2.94; 95% CI: 0.62:5.26). CONCLUSION: Providing any type of sensorimotor therapy decreased time to reach FOF in infants <33weeks. Structured guidelines may help optimize this effect. PMID- 27372636 TI - Assessment of general movements and heart rate variability in prediction of neurodevelopmental outcome in preterm infants. AB - BACKGROUND: Adverse neurologic outcome in preterm infants could be associated with abnormal heart rate (HR) characteristics as well as with abnormal general movements (GMs) in the 1st month of life. AIMS: To demonstrate to what extent GMs assessment can predict neurological outcome in preterm infants in our clinical setting; and to assess the clinical usefulness of time-domain indices of heart rate variability (HRV) in improving predictive value of poor repertoire (PR) GMs in writhing period. STUDY DESIGN: Qualitative assessment of GMs at 1 and 3 months corrected age; 24h electrocardiography (ECG) recordings and analyzing HRV at 1 month corrected age. SUBJECTS: Seventy nine premature infants at risk of neurodevelopmental impairments were included prospectively. OUTCOME MEASURES: Neurodevelopmental outcome was assessed at the age of 2 years corrected. Children were classified as having normal neurodevelopmental status, minor neurologic dysfunction (MND), or cerebral palsy (CP). RESULTS: We found that GMs in writhing period (1 month corrected age) predicted CP at 2 years with sensitivity of 100%, and specificity of 72.1%. Our results demonstrated the excellent predictive value of cramped synchronized (CS) GMs, but not of PR pattern. Analyzing separately a group of infants with PR GMs we found significantly lower values of HRV parameters in infants who later developed CP or MND vs. infants with PR GMs who had normal outcome. CONCLUSIONS: The quality of GMs was predictive for neurodevelopmental outcome at 2 years. Prediction of PR GMs was significantly enhanced with analyzing HRV parameters. PMID- 27372637 TI - The sex ratio at birth in France was unchanged 9months after the 1998 FIFA World Cup. AB - INTRODUCTION: Positive psychological phenomena such as increased feelings of belonging linked to hosting the FIFA World Cup were observed in France 1998 and South Africa 2010. Approximately nine months after South Africa hosted the 2010 World Cup the sex ratio at birth increased significantly. Given the similarity of positive psychological phenomena between the two countries, this study sought to determine if the sex ratio at birth increased in France circa nine months after the 1998 World Cup. METHODS: Anonymized publicly available live birth data from 1994 to 2004 inclusive was obtained from the Insee (Institut National de la Statistique et des Etudes/Economiques - National Institute of Statistics and Economic Studies). For statistical analysis, chi-squared tests were used. RESULTS: The sex ratio at birth for March and April 1999 did not differ significantly from that of the rest of same period from 1996 to 2000 (p=0.558), there was also no significant difference for February and March 1999. CONCLUSION: The sex ratio at birth did not increase in France after it hosted the 1998 World Cup. Possible reasons why the sex ratio at birth did not increase as it did in South Africa include a higher French prevalence of modern contraceptive use and a different kind/level of excitement for the World Cup in France since it has previously hosted large international sports tournaments. The influence of the World Cup on the sex ratio at birth depends on the context of a specific country. PMID- 27372638 TI - Sirtuin 2 Inhibition Improves Cognitive Performance and Acts on Amyloid-beta Protein Precursor Processing in Two Alzheimer's Disease Mouse Models. AB - The neuropathological hallmarks of Alzheimer's disease (AD) are extracellular plaques built up by the accumulation of the amyloid-beta protein precursor (AbetaPP)-derived peptide beta (Abeta), and intracellular tangles of hyperphosphorylated tau protein. Sirtuin 2 (SIRT2) is a member of the sirtuin family, featuring conserved enzymes with deacetylase activity and involved in several cell molecular pathways. We investigated the importance of SIRT2 inhibition in AD. We inhibited SIRT2 by small molecules (AGK-2, AK-7) and examined AbetaPP metabolism in H4-SW neuroglioma cells overexpressing AbetaPP and two AD transgenic mouse models (3xTg-AD and APP23). The in vitro studies suggested that the inhibition of SIRT2 reduced Abeta production; in vivo data showed an improvement of cognitive performance in the novel object recognition test, and an effect on AbetaPP proteolytic processing leading to a reduction of soluble beta-AbetaPP and an increase of soluble alpha-AbetaPP protein. In 3xTg-AD mice, we noticed that total tau protein level rose. Overall, our pre-clinical data support a role for SIRT2 inhibition in the improvement of cognitive performance and the modulation of molecular mechanisms relevant for AD, thus deserving attention as possible therapeutic strategy. PMID- 27372639 TI - Fine Particulate Matter, Residential Proximity to Major Roads, and Markers of Small Vessel Disease in a Memory Study Population. AB - BACKGROUND: Long-term exposure to ambient air pollution has been associated with impaired cognitive function and vascular disease in older adults, but little is known about these associations among people with concerns about memory loss. OBJECTIVE: To examine associations between exposures to fine particulate matter and residential proximity to major roads and markers of small vessel disease. METHODS: From 2004-2010, 236 participants in the Massachusetts Alzheimer's Disease Research Center Longitudinal Cohort participated in neuroimaging studies. Residential proximity to major roads and estimated 2003 residential annual average of fine particulate air pollution (PM2.5) were linked to measures of brain parenchymal fraction (BPF), white matter hyperintensities (WMH), and cerebral microbleeds. Associations were modeled using linear and logistic regression and adjusted for clinical and lifestyle factors. RESULTS: In this population (median age [interquartile range] = 74 [12], 57% female) living in a region with median 2003 PM2.5 annual average below the current Environmental Protection Agency (EPA) standard, there were no associations between living closer to a major roadway or for a 2MUg/m3 increment in PM2.5 and smaller BPF, greater WMH volume, or a higher odds of microbleeds. However, a 2MUg/m3 increment in PM2.5 was associated with -0.19 (95% Confidence Interval (CI): -0.37, -0.005) lower natural log-transformed WMH volume. Other associations had wide confidence intervals. CONCLUSIONS: In this population, where median 2003 estimated PM2.5 levels were below the current EPA standard, we observed no pattern of association between residential proximity to major roads or 2003 average PM2.5 and greater burden of small vessel disease or neurodegeneration. PMID- 27372640 TI - Behavioral and Electrophysiological Correlates of Memory Binding Deficits in Patients at Different Risk Levels for Alzheimer's Disease. AB - Deficits in visual short-term memory (VSTM) binding have been proposed as an early and specific marker for Alzheimer's disease (AD). However, no studies have explored the neural correlates of this domain in clinical categories involving prodromal stages with different risk levels of conversion to AD. We assessed underlying electrophysiological modulations in patients with mild cognitive impairment (MCI), patients in the MCI stages of familial AD carrying the mutation E280A of the presenilin-1 gene (MCI-FAD), and healthy controls. Moreover, we compared the behavioral performance and neural correlates of both patient groups. Participants completed a change-detection VSTM task assessing recognition of changes between shapes or shape-color bindings, presented in two consecutive arrays (i.e., study and test) while event related potentials (ERPs) were recorded. Changes always occurred in the test array and consisted of new features replacing studied features (shape-only) or features swapping across items (shape color binding). Both MCI and MCI-FAD patients performed worse than controls in the shape-color binding condition. Early electrophysiological activity (100-250 ms) was significantly reduced in both clinical groups, particularly over fronto central and parieto-occipital regions. However, shape-color binding performance and their reduced neural correlates were similar between MCI and MCI-FAD. Our results support the validity of the VSTM binding test and their neural correlates in the early detection of AD and highlight the importance of studies comparing samples at different risk for AD conversion. The combined analysis of behavioral and ERP data gleaned with the VSTM binding task can offer a valuable memory biomarker for AD. PMID- 27372641 TI - An 18-mer Peptide Derived from Prosaposin Ameliorates the Effects of Abeta1-42 Neurotoxicity on Hippocampal Neurogenesis and Memory Deficit in Mice. AB - The pathological hallmarks of Alzheimer's disease (AD) include amyloid-beta (Abeta) accumulation, neurofibrillary tangle formation, synaptic dysfunction, and neuronal loss. The present study was performed to investigate the protective effects and mechanism of action of a prosaposin-derived 18-mer peptide (PS18: LSELIINNATEELLIKGL) on mice hippocampal progenitor cell proliferation, neurogenesis, and memory tasks after intracerebroventricular injection of Abeta1 42 peptide. Seven days after Abeta1-42 injection, significant proliferation of hippocampal progenitor cells and memory impairment were evident. Two weeks after Abeta1-42 peptide injection, elevated numbers of surviving 5-bromo-2-deoxyuridine cells and newly formed neurons were detected. Treatment with PS18 attenuated these effects evoked by Abeta1-42. Our data indicate that treatment with PS18 partially attenuated the increase in hippocampal neurogenesis caused by Abeta1-42 induced neuroinflammation and prevented memory deficits associated with increased numbers of activated glial cells. We observed an increase in ADAM10 and decreases in BACE1, PS1/2, and AbetaPP protein levels, suggesting that PS18 enhances the nonamyloidogenic AbetaPP cleavage pathway. Importantly, our results further showed that PS18 activated the PI3K/Akt pathway, phosphorylated GSK-3alpha/beta, and, as a consequence, exerted a neuroprotective effect. In addition, PS18 showed a protective effect against Abeta1-42-induced neurotoxicity via suppression of the caspase pathway; upregulation of Bcl-2; downregulation of BAX, attenuating mitochondrial damage; and inhibition of caspase-3. These findings suggest that PS18 may provide a valuable therapeutic strategy for the treatment of progressive neurodegenerative diseases, such as AD. PMID- 27372642 TI - Formulaic Language in People with Probable Alzheimer's Disease: A Frequency-Based Approach. AB - BACKGROUND: Language change can be a valuable biological marker of overall cognitive change in Alzheimer's disease (AD) and other forms of dementia. Previous reports have described increased use of language formulas in AD, i.e., combinations likely processed in a holistic manner. Words that commonly occur together are more likely to become a formula. OBJECTIVE: To determine if frequency of co-occurrence as one indicator for formulaic language can distinguish people with probable AD from controls and if variables are sensitive to time post-symptom onset. METHODS: We developed the Frequency in Language Analysis Tool (FLAT), which indicates degrees of formulaicity in an individual language sample. The FLAT accomplishes this by comparing individual language samples to co-occurrence data from the British National Corpus (BNC). Our analysis also contained more conventional language variables in order to assess novel contributions of the FLAT. We analyzed data from the Pitt Corpus, which is part of DementiaBank. RESULTS: Both conventional and co-occurrence variables were able to distinguish AD and control groups. According to co-occurrence data, people with probable AD produced more formulaic language than controls. Only co occurrence variables correlated with disease progression. DISCUSSION: Frequency of word co-occurrences is one indicator for formulaicity and a valuable contribution to characterizing language change in AD. PMID- 27372643 TI - Partial Amelioration of Synaptic and Cognitive Deficits by Inhibiting Cofilin Dephosphorylation in an Animal Model of Alzheimer's Disease. AB - The loss of synaptic structure and function has been linked to the cognitive impairment of Alzheimer's disease (AD). Dysregulation of the actin cytoskeleton, which plays a key role in regulating the integrity of synapses and the transport of synaptic proteins, has been suggested to contribute to the pathology of AD. In this study, we found that glutamate receptor surface expression and synaptic function in frontal cortical neurons were significant diminished in a familial AD (FAD) model, which was correlated with the reduction of phosphorylated cofilin, a key protein regulating the dynamics of actin filaments. Injecting a cofilin dephosphorylation inhibitory peptide to FAD mice led to the partial rescue of the surface expression of AMPA and NMDA receptor subunits, as well as the partial restoration of AMPAR- and NMDAR-mediated synaptic currents. Moreover, the impaired working memory and novel object recognition memory in FAD mice were partially ameliorated by injections of the cofilin dephosphorylation inhibitory peptide. These results suggest that targeting the cofilin-actin signaling holds promise to mitigate the physiological and behavioral abnormality in AD. PMID- 27372645 TI - Physical and Cognitive Stimulation Using an Exergame in Subjects with Normal Aging, Mild and Moderate Cognitive Impairment. AB - BACKGROUND: The use of Serious exerGames (SeG) as enriched environments (EE), which promotes cognitive simulation with physical activity in a positive emotional context, has been proposed to represent a powerful method to slow down the decline due to neurodegenerative diseases (ND), such as Alzheimer's disease (AD). However, so far, no SeG targeting EE has been tested in ND subjects. OBJECTIVE: This study aimed at evaluating the usability and short-term training effects of X-Torp, an action SeG designed for elderly ND subjects with mild cognitive impairment (MCI) and AD. METHODS: X-Torp is a SeG played using the Microsoft(r) KinectTM. 10 ND subjects and 8 healthy elderly controls (HEC) were enrolled in a 1-month program with three training sessions per week. Usability was evaluated through game time, game performance, the aerobic intensity level reached, perceived emotions, and perceived usability. RESULTS: All participants successfully completed the training program. ND subjects played less and had a lower game performance compared to HEC. During the sessions, ND subjects maintained a light intensity of aerobic activity, while HEC maintained a moderate intensity. Both groups experienced only positive emotions, and reported a 'moderate' to 'high' perceived competence, a 'moderate' game difficulty, and a 'high' interest in the game. CONCLUSION: Usability results suggest that X-Torp represents a usable EE for healthy subjects and persons with MCI and AD. However, in order to reach moderate or high intensity of aerobic activity, X-Torp control modes should be adapted to become more physically stimulating. PMID- 27372644 TI - Reversal of ApoE4-Driven Brain Pathology by Vascular Endothelial Growth Factor Treatment. AB - Apolipoprotein E4 (ApoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), is associated with increased neurodegeneration and vascular impairments. Vascular endothelial growth factor (VEGF), originally described as a key angiogenic factor, has recently been shown to play a crucial role in the nervous system. The objective of this research is to examine the role of VEGF in mediating the apoE4-driven pathologies. We show that hippocampal VEGF levels are lower in apoE4 targeted replacement mice compared to the corresponding apoE3 mice. This effect was accompanied by a specific decrease in both VEGF receptor-2 and HIF1-alpha. We next set to examine whether upregulation of VEGF can reverse apoE4-driven pathologies, namely the accumulation of hyperphosphorylated tau (AT8) and Abeta42, and reduced levels of the pre-synaptic marker, VGluT1, and of the ApoE receptor, ApoER2. This was first performed utilizing intra-hippocampal injection of VEGF-expressing-lentivirus (LV-VEGF). This revealed that LV-VEGF treatment reversed the apoE4-driven cognitive deficits and synaptic pathologies. The levels of Abeta42 and AT8, however, were increased in apoE3 mice, masking any potential effects of this treatment on the apoE4 mice. Follow-up experiments utilizing VEGF-expressing adeno-associated-virus (AAV-VEGF), which expresses VEGF specifically under the GFAP astrocytic promoter, prevented this effects on apoE3 mice, and reversed the apoE4-related increase in Abeta42 and AT8. Taken together, these results suggest that apoE4-driven pathologies are mediated by a VEGF dependent pathway, resulting in cognitive impairments and brain pathology. These animal model findings suggest that the VEGF system is a promising target for the treatment of apoE4 carriers in AD. PMID- 27372646 TI - Diagnostic Accuracy of MRI and Additional [18F]FDG-PET for Behavioral Variant Frontotemporal Dementia in Patients with Late Onset Behavioral Changes. AB - BACKGROUND: Neuroimaging has a reasonable accuracy to differentiate behavioral variant frontotemporal dementia (bvFTD) from other neurodegenerative disorders, its value for the differentiation of bvFTD among subjects with acquired behavioral disturbances is unknown. OBJECTIVE: To determine the diagnostic accuracy of MRI, additional [18F]FDG-PET, and their combination for bvFTD among subjects with late onset behavioral changes. METHODS: Patients with late onset behavioral changes referred to a memory clinic or psychiatric services were included. At baseline, 111 patients had a brain MRI scan and 74 patients received an additional [18F]FDG-PET when the MRI was inconclusive. The consensus diagnosis after two-year-follow-up was used as the gold standard to calculate sensitivity and specificity for baseline neuroimaging. RESULTS: 27 patients had probable/definite bvFTD and 84 patients had a non-bvFTD diagnosis (primary psychiatric diagnosis or other neurological disorders). MRI had a sensitivity of 70% (95% CI 52-85%) with a specificity of 93% (95% CI 86-97%). Additional [18F]FDG-PET had a sensitivity of 90% (95% CI 66-100%) with a specificity of 68% (95% CI 56-79%). The sensitivity of combined neuroimaging was 96% (95% CI 85 100%) with a specificity of 73% (95% CI 63-81%). In 66% of the genetic FTD cases, MRI lacked typical frontotemporal atrophy. 40% of cases with a false positive [18F]FDG-PET scan had a primary psychiatric diagnosis. CONCLUSION: A good diagnostic accuracy was found for MRI and additional [18F]FDG-PET for bvFTD in patients with late onset behavioral changes. Caution with the interpretation of neuroimaging results should especially be taken in cases with a genetic background and in cases with a primary psychiatric differential diagnosis where [18F]FDG-PET is the only abnormal investigation. PMID- 27372647 TI - Neurocognitive Deficits Distinguishing Mild Dementia with Lewy Bodies from Mild Alzheimer's Disease are Associated with Parkinsonism. AB - BACKGROUND: The cognitive profile of mild dementia with Lewy bodies (DLB) versus mild Alzheimer's disease (AD) has not been extensively studied, and the relation of cognitive deficits to the core diagnostic criteria for DLB (fluctuations, visual hallucinations, and parkinsonism) remains poorly understood. OBJECTIVE: To compare the cognitive profile in patients with mild DLB to patients with mild AD and investigate the relation between cognitive deficits distinguishing DLB from AD and the core diagnostic features in DLB. METHODS: Patients with mild dementia were recruited from the southwestern part of Norway and patients diagnosed with probable AD (n = 113) or probable DLB (n = 77) were included. The DLB core diagnostic symptoms were assessed using standardized clinical measures, and standardized neurocognitive tests assessing attention, language, memory, and visuospatial functions were administered. Univariate and multivariate comparisons of cognitive tests were performed, and tests distinguishing between AD and DLB were subjected to correlational analyses with the core diagnostic symptoms. RESULTS: DLB patients performed worse than AD patients on test of visuoconstruction, but not visual perception and on all tests involving attention and executive functions, except verbal fluency. The multivariate model distinguished between DLB and AD with a sensitivity of 74% and a specificity of 82%. Tests where DLB performed worse than AD were highly correlated with degree of parkinsonism, but not with cognitive fluctuations or visual hallucinations. CONCLUSIONS: The cognitive profile in mild DLB can be useful in distinguishing AD from DLB. The strong relation between relative deficits in DLB and parkinsonism warrants further studies. PMID- 27372648 TI - Alzheimer's Disease: Assessing the Role of Spirochetes, Biofilms, the Immune System, and Amyloid-beta with Regard to Potential Treatment and Prevention. AB - Alzheimer's disease (AD) is an infectious disease caused by spirochetes, and these spirochetes form biofilms, which attract the innate immune system. The innate immune system first responder, Toll-like receptor 2, generates both NF kappaB and TNF-alpha which try to kill the spirochetes in the biofilm, but cannot penetrate the "slime". NF-kappaB is also responsible for the generation of amyloid-beta (Abeta) which itself is anti-microbial. Abeta cannot penetrate the biofilm either, and its accumulation leads to destruction of the cerebral neurocircuitry. Treatment with penicillin (as in tertiary syphilis, the comparator to AD) is outlined; a biofilm dispersing agent may need to be added to the protocol. PMID- 27372649 TI - Impaired VEGF Signaling in Lungs with Hypoplastic Esophageal Atresia and Effects on Branching Morphogenesis. AB - BACKGROUND/AIMS: Patients with esophageal atresia (EA) and tracheoesophageal fistula (TEF) often suffer chronic respiratory tract disease. We previously reported that primary lung maldevelopment caused by deficient branching of embryonal airways in experimental EA-TEF was induced by Adriamycin. In this study, we investigated the Vascular endothelial growth factor (VEGF) pathway in the developing lung in an EA-TEF rat model. We further analyzed the effect of recombinant VEGF treatment in vitro on branching morphogenesis of embryo lungs in experimental EA-TEF. METHODS: Pregnant rats received either Adriamycin or vehicle on E7, E8 and E9. Lungs were recovered at E15, E18 and E21. Expression of VEGF and receptors (Flk-1 and Flt-1) were assessed by quantitative PCR, immunohistochemistry and immunoblotting. E13 lungs were cultured for 72 hours with 50 ng/mL of recombinant rat VEGF in serum-free medium. The rates of increase in bud count and airway contour were evaluated. RESULTS: Our results showed a significant downregulation of VEGF during pseudoglandular and canalicular stages. In contrast, there were significantly higher levels of the Flt-1 receptor in the canalicular stage, which may represent a compensatory response to decreased VEGF. However, both variables returned to normal levels at the saccular stage. Exogenous VEGF treatment enhanced hypoplastic lung growth, evidenced by the increase in bud count and airway contour. CONCLUSIONS: A VEGF signaling defect possibly plays an important role in defective embryonic airway branching. Additionally, VEGF treatment may accelerate lung growth in EA-TEF lungs. PMID- 27372650 TI - Overexpression of Phosphoserine Aminotransferase 1 (PSAT1) Predicts Poor Prognosis and Associates with Tumor Progression in Human Esophageal Squamous Cell Carcinoma. AB - BACKGROUND/AIMS: Phosphoserine aminotransferase 1 (PSAT1) is over-expressed in many carcinoma tissues, however little is known regarding its expression and function in esophageal carcinogenesis. This study investigated the expression of PSAT1 in human esophageal squamous cell carcinoma (ESCC) tissues to determine the relationship between PSAT1 expression and clinicopathological factors. METHODS: The expression of PSAT1 in 64 surgical resections from esophageal carcinogenesis patients was examined by quantitative RT-PCR and immunohistochemistry and the results were compared with clinicopathological factors. In vitro experiments were performed in ESCC cells overexpressing PSAT1 to measure cell viability and invasion. Tumor formation in vivowas examined by injection of tumor cells into immunocompromised mice subcutaneously. RESULTS: PSAT1 expression was elevated in ESCC tissues compared to normal esophageal tissues. Increased PSAT1 expression was significantly associated with stage of disease, lymph node metastasis, distant metastasis and poor prognosis. In vitro, PSAT1 overexpression promoted ESCC cell proliferation and matrigel invasion. In vivo, injection of mice with ECSS cells overexpressing PSAT1 enhanced tumor formation. Western blot analysis revealed that PSAT1 upregulated the expression and/or activity of GSK3beta/Snail. CONCLUSION: PSAT1 plays a crucial role in the development of ESCC and predicts poor survival. Therefore, PSAT1 may be a promising novel anticancer therapeutic target. PMID- 27372651 TI - Geniposide Prevents Hypoxia/Reoxygenation-Induced Apoptosis in H9c2 Cells: Improvement of Mitochondrial Dysfunction and Activation of GLP-1R and the PI3K/AKT Signaling Pathway. AB - BACKGROUND/AIMS: Myocardial ischemia/reperfusion injury is a major cause of morbidity and mortality associated with coronary heart disease. Many studies have demonstrated that natural products are promising chemotherapeutic drugs counteracting the loss of cardiomyocytes. Thus, the purpose of the present study was to investigate the effects of geniposide, a traditional Chinese herb extract from Gardenia jasminoides J. Ellis, on cardiomyocyte apoptosis induced by hypoxia/reoxygenation (H/R) in H9c2 cells, and their underlying mechanisms. METHODS: Cell viability and apoptosis ratio were assessed using the cell counting kit-8 assay and Annexin V/propidium iodide (PI) staining. The concentrations of lactate dehydrogenase (LDH), intracellular total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were detected by microplate reader. The production of reactive oxygen species/reactive nitrogen species (ROS/RNS), the level of mitochondrial calcium, and mitochondrial membrane potential depolarization were measured by confocal laser scanning microscopy. Mitochondrial morphology was visualized using transmission electron microscopy. The expressions of Bcl-2 mRNA and Caspase-3 mRNA were measured by reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of cleaved caspase-3, Bcl-2, Bax, AKT, p AKTserine473, cytochrome-c were detected by western bloting. RESULTS: Geniposide pretreatment increased cell viability, decreased LDH levels in the supernatant, and inhibited cardiomyocyte apoptosis caused by H/R. Furthermore, geniposide reversed mitochondrial dysfunction by decreasing oxidative stress products (ROS/RNS and MDA), increasing anti-oxidative enzyme (T-SOD) level, improving mitochondrial morphology, attenuating mitochondrial calcium overload and blunting depolarization of mitochondrial membrane. Moreover, geniposide pretreatment increased Bcl-2 level and decreased Bax level, thus enhancing the Bcl-2/Bax ratio. Consistent with the above result, Bcl-2 mRNA expression was upregulated and caspase-3 mRNA expression was downregulated by geniposide. In addition, geniposide decreased the protein expression of cleaved caspase-3 and cytochrome-c and increased the level p-AKTserine473. The protective effects of geniposide were partially reversed by glucagon-like pepitide-1 receptor antagonist exendin-(9-39) and the phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002. CONCLUSIONS: Our results suggest that geniposide pretreatment inhibits H/R-induced myocardial apoptosis by reversing mitochondrial dysfunction, an effect in part due to activation of GLP-1R and PI3K/AKT signaling pathway. PMID- 27372652 TI - Phytoextraction, phytotransformation and rhizodegradation of ibuprofen associated with Typha angustifolia in a horizontal subsurface flow constructed wetland. AB - Widespread occurrence of trace pharmaceutical residues in aquatic environments is of great concerns due to the potential chronic toxicity of certain pharmaceuticals including ibuprofen on aquatic organisms even at environmental levels. In this study, the phytoextraction, phytotransformation and rhizodegradation of ibuprofen associated with Typha angustifolia were investigated in a horizontal subsurface flow constructed wetland system. The experimental wetland system consisted of a planted bed with Typha angustifolia and an unplanted bed (control) to treat ibuprofen-loaded wastewater (~107.2 MUg L(-1)). Over a period of 342 days, ibuprofen was accumulated in leaf sheath and lamina tissues at a mean concentration of 160.7 ng g(-1), indicating the occurrence of the phytoextraction of ibuprofen. Root-uptake ibuprofen was partially transformed to ibuprofen carboxylic acid, 2-hydroxy ibuprofen and 1 hydroxy ibuprofen which were found to be 1374.9, 235.6 and 301.5 ng g(-1) in the sheath, respectively, while they were 1051.1, 693.6 and 178.7 ng g(-1) in the lamina. The findings from pyrosequencing analysis of the rhizosphere bacteria suggest that the Dechloromonas sp., the Clostridium sp. (e.g. Clostridium saccharobutylicum), the order Sphingobacteriales, and the Cytophaga sp. in the order Cytophagales were most probably responsible for the rhizodegradation of ibuprofen. PMID- 27372653 TI - 3-Fluorophenmetrazine, a fluorinated analogue of phenmetrazine: Studies on in vivo metabolism in rat and human, in vitro metabolism in human CYP isoenzymes and microbial biotransformation in Pseudomonas Putida and wastewater using GC and LC coupled to (HR)-MS techniques. AB - Wastewater-based epidemiology (WBE) as means to estimate illicit drug and new psychoactive substance (NPS) consumption with spatial and temporal resolution is gaining increasing attention. In order to evaluate a given NPS using WBE, in vivo metabolism and microbial biotransformation of excretion products and unchanged compounds need evaluation. The aims of this study were to identify in vivo phase I and II metabolites of the NPS 3-fluorophenmetrazine (3-FPM) in human and rat urine and study the in vitro contribution of Cytochrome P450 (CYP) isoenzymes in phase I metabolism. Additionally, to study microbial biotransformation products (MBPs) of 3-FPM from incubations in wastewater and in a wastewater isolated Pseudomonas Putida strain. To these aims gas chromatography and liquid chromatography coupled to mass spectrometry were applied. Metabolites and MBPs were isolated from urine and microbial incubations after solid phase extraction and precipitation with or without enzymatic conjungate cleaving. The main transformation pathways were N-oxidation, aryl hydroxylation and subsequent O methylation, alkyl hydroxylation, oxidation, and degradation of the ethyl-bridge yielding the O/N-bis-dealkylated metabolite, combinations thereof and further glucuronidation or sulfations. The main excretion products in the human urine sample were the unchanged compound and the N-oxide, and the main MBPs were the N oxide and hydroxylation with subsequent oxidations on the alpha-methyl position. Based on these findings, the proposed strategy for WBE analysis of 3-FPM is quantitative determination of unchanged 3-FPM together with qualitative verification of a number of selected metabolites to verify consumption and rule out discharge. PMID- 27372654 TI - Epithelial-mesenchymal transition of the retinal pigment epithelium causes choriocapillaris atrophy. AB - Epithelial-to-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is commonly observed at sites of choroidal neovascularization in patients suffering from age-related macular degeneration. To learn in an experimental model how RPE EMT affects the biology of the choroidal vasculature, we studied transgenic mice (betaB1-TGF-beta1) with ocular overexpression of transforming growth factor-beta1 (TGF-beta1). RPE EMT was detectable at postnatal day (P)1 and included marked structural and functional alterations such as loss of the outer blood-retina barrier and reduced mRNA expression of the RPE-characteristic molecules Rlbp1, Rpe65, Rbp1 and Vegfa. Moreover, vascular endothelial growth factor (VEGF) was not detectable by immunohistochemistry at the RPE/choroid interface, while RPE cells stained intensely for alpha-smooth muscle actin. The choriocapillaris, the characteristic choroidal capillary network adjacent to the RPE, developed normally and was not obviously changed in embryonic transgenic eyes but was absent at P1 indicating its atrophy. At around the same time, photoreceptors stopped to differentiate and photoreceptor apoptosis was abundant in the second week of life. Structural changes were also seen in the retinal vasculature of transgenic animals, which did not form intraretinal vessels, and the hyaloid vasculature, which did not regress. In addition, the amounts of retinal HIF-1alpha and its mRNA were markedly reduced. We conclude that high amounts of active TGF-beta1 in the mouse eye cause transdifferentiation of the RPE to a mesenchymal phenotype. The loss of epithelial differentiation leads to the diminished synthesis of RPE-characteristic molecules including that of VEGF. Lack of RPE-derived VEGF causes atrophy of the choriocapillaris, a scenario that disrupts photoreceptor differentiation and finally results in photoreceptor apoptosis. Lack of retinal vessel formation and of hyaloid vessel regression might be caused by the decrease in the metabolic requirements of the neuroretina leading to low amounts of retinal HIF-1alpha. In summary, our data indicate that failure of RPE differentiation may well precede and cause atrophy of the choriocapillaris. In contrast, RPE EMT is not sufficient to cause choroidal neovascularization. PMID- 27372655 TI - Severe adverse skin reaction and desensitization to sorafenib. PMID- 27372656 TI - Food allergy education program at an elementary school: A pilot study. PMID- 27372657 TI - Objective measurement of frequency and pattern of nocturnal cough in children with asthma exacerbation. AB - BACKGROUND: Although a number of patients with asthma report experiencing persistent cough during sleep, it has not yet been objectively investigated. OBJECTIVE: To classify cough severity and evaluate a characteristic pattern of cough frequency in children with asthma using an objective cough monitoring system. METHODS: An objective cough monitoring system that specialized in children was used to measure cough frequency and nocturnal cough patterns. Coughs were recorded with microphone and accelerometer and analyzed using a customized software program. The number of nocturnal coughs and the pattern of cough frequency in 30-minute intervals were measured along with the severity of each asthma exacerbation, and the results were compared with children without asthma. RESULTS: The total overnight cough count of 34 children with asthma was higher than that of 15 children without asthma (P < .001). The total overnight cough count in children with severe asthma exacerbation was higher than that in children with moderate asthma exacerbation (P < .05). The cough counts were significantly increased at the time of falling asleep and waking. This pattern was not observed in children without asthma. The total cough counts and cough patterns in children with asthma were not affected by sex, age, cause of asthma exacerbation, or therapy. CONCLUSION: Our data indicate huge cough counts and characteristic nocturnal cough patterns in children with asthma. Objective and precise cough monitoring is useful for the management of childhood asthma. PMID- 27372658 TI - PM2.5 particulates and metallic elements (Ni, Cu, Zn, Cd and Pb) study in a mixed area of summer season in Shalu, Taiwan. AB - PM2.5 has become an important environmental issue in Taiwan during the past few years. Moreover, electricity increased significantly during the summertime and TTPP generated by coal burning base is the main electricity provider in central Taiwan. Therefore, summer season has become the main research target in this study. The ambient air concentrations of particulate matter PM2.5 and PM10 collected by using VAPS at a mixed characteristic sampling site were studied in central Taiwan. The results indicated that the average daytime PM2.5 and PM10 particulate concentrations were occurred in May and they were 44.75 and 57.77 ug/m3 in this study. The results also indicated that the average nighttime PM2.5 and PM10 particulate concentrations were occurred in June and they were 38.19 and 45.79 ug/m3 in this study. The average PM2.5/PM10 ratios were 0.7 for daytime, nighttime and 24-h sampling periods in the summer for this study. This value was ranked as the lowest ratios when compared to the other seasons in previous study. Noteworthy, the results further indicated that the metallic element Pb has the mean highest concentrations for 24-h, daytime and nighttime sampling periods when compared to those of the other metallic elements (Ni, Cu, Zn and Cd). The average mean highest metallic Pb concentrations in PM10 were 110.7, 203.0 and 207.2 ng/m3 for 24-h, daytime and nighttime sampling periods in this study. And there were 59.53, 105.2 and 106.6 ng/m3 for Pb in PM2.5 for 24-h, daytime and nighttime sampling periods, respectively. Moreover, the results further indicated that mean metallic element Pb concentrations on PM2.5 and PM10 were all higher than those of the other elements for 24 h, day and nighttime. PMID- 27372659 TI - Occurrence and profiles of polybrominated diphenyl ethers (PBDEs) in riverine sediments of Shanghai: a combinative study with human serum from the locals. AB - Herein, we studied the occurrence and profiles of thirteen PBDE congeners in 30 river sediment samples from Shanghai, China. The concentrations of Sigma13PBDEs ranged from 110 to 13,071 pg g -1 dw, with an average value of 2,841 pg g -1 dw. BDE-209 was the predominant congener accounting for more than 65 % of total PBDEs, demonstrating that the major source of PBDEs in sediment samples was associated with the prevalent use of technical deca-BDE products. Moreover, low brominated BDEs in sediments also came from the degradation of higher brominated BDEs. In addition, taking into consideration of dietary exposure, PBDEs in serum samples collected from the locals were also detected with range of 419-26,744 pg g-1 (average 5,561 pg g -1), which suggested a relatively low burden of PBDEs contamination to human body compared with the condition in other place. And in serum, low brominated compounds constituted the majority of total PBDE congeners. PMID- 27372660 TI - Farmers' Preferences for Future Agricultural Land Use Under the Consideration of Climate Change. AB - Cultural landscapes in Austria are multifunctional through their simultaneous support of productive, habitat, regulatory, social, and economic functions. This study investigates, if changing climatic conditions in Austria will lead to landscape change. Based on the assumption that farmers are the crucial decision makers when it comes to the implementation of agricultural climate change policies, this study analyzes farmers' decision-making under the consideration of potential future climate change scenarios and risk, varying economic conditions, and different policy regimes through a discrete choice experiment. Results show that if a warming climate will offer new opportunities to increase income, either through expansion of cash crop cultivation or new land use options such as short term rotation forestry, these opportunities will almost always be seized. Even if high environmental premiums were offered to maintain current cultural landscapes, only 43 % of farmers would prefer the existing grassland cultivation. Therefore, the continuity of characteristic Austrian landscape patterns seems unlikely. In conclusion, despite governmental regulations of and incentives for agriculture, climate change will have significant effects on traditional landscapes. Any opportunities for crop intensification will be embraced, which will ultimately impact ecosystem services, tourism opportunities, and biodiversity. PMID- 27372661 TI - Plasmacytoid dendritic cells in skin lesions of classic Kaposi's sarcoma. AB - Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFNs), which allows them to provide anti-viral resistance and to link the innate and adaptive immunity by controlling the function of myeloid DCs, lymphocytes, and natural killer cells. pDCs are involved in the pathogenesis of several infectious [especially viral, such as Molluscum contagiosum (MC)], inflammatory/autoimmune, and neoplastic entities. Kaposi's sarcoma (KS) is a multifocal, systemic lympho-angioproliferative tumor associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Microscopy typically exhibits a chronic inflammatory lymphoplasmacytic infiltrate in addition to the vascular changes and spindle cell proliferation. Despite the extensive research done on the immune evasion strategies employed by KSHV, pDCs role in relation to KS has only rarely been investigated. Given this, we intend to investigate pDC occurrence and activity in the skin lesions of KS. Immunohistochemical staining for BDCA-2 (specific pDC marker) and MxA (surrogate marker for local type I IFN production) was performed on classic KS (n = 20) with the control group comprising inflamed MC (n = 20). As expected, BDCA-2+ pDCs were present in abundance with diffuse and intense MxA expression (indicative of local type I IFN production) in all inflamed MC cases (20 of 20, 100 %). Though present in all the KS cases, pDCs were significantly less abundant in KS than in inflamed MC cases, and MxA expression was patchy/weak in most KS cases. In summary, pDCs are part of the inflammatory host response in KS; however, they were generally low in number with decreased type I IFN production which is probably related to KSHV's ability to evade the immune system through the production of different viral proteins capable of suppressing IFN production as well as pDC function. PMID- 27372662 TI - Dental treatments, tooth extractions, and osteonecrosis of the jaw in Japanese patients with rheumatoid arthritis: results from the IORRA cohort study. AB - This study aimed to evaluate dental treatments, tooth extractions, and osteonecrosis of the jaw (ONJ) in Japanese patients with rheumatoid arthritis (RA). Patients with RA enrolled in our cohort completed self-administered questionnaires, which included questions regarding their dental treatments, tooth extractions by dentists during the past 6 months, and past history of ONJ. The history of ONJ was validated with the patients' medical records. Logistic regression was used to determine the association of variables with dental treatments and tooth extractions during the past 6 months. Among 5695 Japanese patients with RA who responded to the questionnaires (mean age, 61.0 years; 85.6 % female), 2323 patients (40.8 %) and 378 patients (6.6 %) reported having had dental treatments and tooth extractions performed by a dentist within the past 6 months, respectively. In multivariate models, advanced age was significantly (P < 0.0001) associated with both dental treatments and tooth extractions during the prior 6-month period, and ever smoking was significantly (P = 0.023) correlated with tooth extractions during that time. Among patients who reported a history of ONJ, we confirmed five cases of ONJ with patient medical records. The prevalence of ONJ was 0.094 % among all RA patients and 0.26 % among female RA patients >=65 years of age (n = 1888). Our data suggest that more than a few Japanese patients with RA have dental complications that require care by dentists, and that Japanese rheumatologists and dentists should cooperate to improve dental health in patients with RA. PMID- 27372663 TI - Raloxifene and Tamoxifen Reduce PARP Activity, Cytokine and Oxidative Stress Levels in the Brain and Blood of Ovariectomized Rats. AB - It is well known that 17beta-estradiol (E2) has an antioxidant role on neurological systems in the brain. Raloxifene (RLX) and tamoxifen (TMX) are selective estrogen receptor modulators. An E2 deficiency stimulates mitochondrial functions for promoting apoptosis and increasing reactive oxygen species (ROS) production. However, RLX and TMX may reduce the mitochondrial ROS production via their antioxidant properties in the brain and erythrocytes of ovariectomized (OVX) rats. We aimed to investigate the effects of E2, RLX, and TMX on oxidative stress, apoptosis, and cytokine production in the brain and erythrocytes of OVX rats.Forty female rats were divided into five groups. The first group was used as a control group. The second group was the OVX group. The third, fourth, and fifth groups were OVX + E2, OVX + TMX, and OVX + RLX groups, respectively. E2, TMX, and RLX were given subcutaneously to the OVX + E2 and OVX + TMX, OVX + RLX groups for 14 days after the ovariectomy respectively.While brain and erythrocyte lipid peroxidation levels were high in the OVX group, they were low in the OVX + E2, OVX + RLX, and OVX + TMX groups. OVX + E2, OVX + RLX, and OVX + TMX treatments increased the lowered glutathione peroxidase activity in erythrocytes and the brain and reduced glutathione and vitamin E concentrations in the brain. beta carotene and vitamin A concentrations in the brain and TNF-alpha and interleukin (IL)-1beta levels in the plasma of the five groups were not significantly changed by the treatments. However, increased plasma IL-4 levels and Western blot results for brain poly (ADP-ribose) polymerase (PARP) in the OVX groups were decreased by E2, TMX, and RLX treatments, although proapoptotic procaspase 3 and 9 activities were increased by the treatments.In conclusion, we observed that E2, RLX, and TMX administrations were beneficial on oxidative stress, inflammation, and PARP levels in the serum and brain of OVX rats by modulating antioxidant systems, DNA damage, and cytokine production. PMID- 27372665 TI - [Not Available]. PMID- 27372666 TI - [Not Available]. PMID- 27372664 TI - The significance of early screening with echocardiography in eosinophilic granulomatosis with polyangiitis. AB - Loffler endocarditis is a serious complication of idiopathic hypereosinophilic syndrome characterized by a peculiar type of fibrosing endocarditis. It results in heart failure due to restrictive cardiomyopathy and systemic embolism due to intracardiac thrombus. Here we present a case of a 57-year-old man with Loffler endocarditis concomitant with eosinophilic granulomatosis with polyangiitis. A thrombus in the left ventricular apex was noted on transthoracic echocardiography performed as a screening of left ventricular dilatation, which seemed to be a typical finding of Loffler endocarditis. But there were no findings that indicated restrictive cardiomyopathy. He was diagnosed with Loffler endocarditis at the thrombotic stage and was given methylprednisolone. The thrombus got markedly smaller within 1 month after initiation of the medical treatment. He has been doing well for more than 2 years since then without eosinophilia or left ventricular thrombosis. In the present case, we could successfully detect the thrombus in the left ventricular apex with echocardiography before the occurrence of embolism and provide early medical treatment. Early detection and initiation of medical treatment are extremely important to treat this unusual but often life threatening condition because methylprednisolone is effective in the necrotic stage and thrombotic stage. PMID- 27372667 TI - [Not Available]. PMID- 27372668 TI - [Not Available]. PMID- 27372669 TI - [Not Available]. PMID- 27372670 TI - [Not Available]. PMID- 27372672 TI - [Not Available]. PMID- 27372671 TI - Survey of smokefree signage at playgrounds: the potential value of comparisons with dog control signage. PMID- 27372673 TI - [Not Available]. PMID- 27372674 TI - [Not Available]. PMID- 27372675 TI - [Not Available]. PMID- 27372676 TI - [Not Available]. PMID- 27372677 TI - [Not Available]. PMID- 27372678 TI - [Not Available]. PMID- 27372679 TI - [Not Available]. PMID- 27372680 TI - [Not Available]. PMID- 27372681 TI - [Not Available]. PMID- 27372682 TI - [Not Available]. PMID- 27372683 TI - [Not Available]. PMID- 27372684 TI - [Not Available]. PMID- 27372685 TI - [Not Available]. PMID- 27372686 TI - [Not Available]. PMID- 27372687 TI - [Not Available]. PMID- 27372688 TI - [Not Available]. PMID- 27372690 TI - [Not Available]. PMID- 27372689 TI - [Not Available]. PMID- 27372691 TI - [Not Available]. PMID- 27372692 TI - [Not Available]. PMID- 27372693 TI - [Not Available]. PMID- 27372694 TI - [Not Available]. PMID- 27372695 TI - [Not Available]. PMID- 27372696 TI - [Not Available]. PMID- 27372697 TI - [Not Available]. PMID- 27372699 TI - [Not Available]. PMID- 27372698 TI - [Not Available]. PMID- 27372700 TI - [Not Available]. PMID- 27372701 TI - [Not Available]. PMID- 27372702 TI - [Not Available]. PMID- 27372703 TI - [Not Available]. PMID- 27372704 TI - [Not Available]. PMID- 27372705 TI - [Not Available]. PMID- 27372706 TI - [Not Available]. PMID- 27372707 TI - Analysis of mammographic diagnostic errors in breast clinic. AB - Mammography is the gold standard for detection of early breast cancer and it is still the only diagnostic tool which shows reduction of the mortality from that. Despite that, there is a high chance of false negatives that can lead to diagnostic errors resulting in delays of treatment and worsening of prognosis. The aim of this study is to analyze the rate of false negative in mammography and assess the source of diagnostic errors. Two radiologists have retrospectively evaluated 500 mammograms performed between January 2008 and December 2011 in Breast Imaging Clinic. 250 patients (Group A) had been operated for breast cancer and 250 patients (Group B) were healthy woman submitted to mammography according to the guideline for early detection of breast cancer. In Group A, 138 patients (55.2 %) were true missed cancer, 61 had minimal sign (24.4 %) and 53 were false negative (FN) (20.4 %). The source of errors amongst the FN were in 42 % of cases due to perception, in 15 % to interpretation, in 10 % to subtle/unusual lesion characteristics, in 9 % error for satisfaction of search, in 7 % to inherent limitations of mammography, in 4 % to poor technique and 13 % for inadequate clinical management. The diagnostic errors in breast clinic services are not negligible. The largest number of FN results from perception errors, misinterpretation and inadequate clinical management. These can be related to factors such as inattention, fatigue or lack of experience. To reduce it, it is necessary to have a dedicated multidisciplinary staff and adequate equipment and workloads. PMID- 27372708 TI - Evaluation of diffusion-weighted imaging (DWI) and MR spectroscopy (MRS) as early response biomarkers in cervical cancer patients. AB - PURPOSE: To prospectively assess whether choline levels and Apparent Diffusion Coefficient (ADC) values within cervical cancers before, during, and after non surgical therapy are predictive of tumour response. PATIENTS AND METHODS: Patients undergoing MR examination for staging of cervical cancer, candidate for non-surgical therapy, were prospectively enrolled. According to the status at the end of therapies, patients were divided into responders and non-responders. The final outcome after a 5-year follow-up was classified as No Evidence of Disease (NED) or Progression of Disease (PD). Baseline values of mean ADC and Cho/H2O were compared between responders and non-responders, as well as between patients with NED and PD. The percent variation of ADC and Cho/H2O values over time was compared. P values <0.05 were considered significant. RESULTS: 16 patients were included. There was no significant difference at baseline between responders (n = 12) and non-responders (n = 4), nor between NED (n = 11) PD patients (n = 5), in ADC values and Cho/H2O ratio. There was no significant difference in percent variation of ADC values and of Cho/H2O, comparing responders and non-responders. There was a significant increase in absolute values of ADC from the initial to mid-therapy MRI (p = 0.0001), while Cho/H2O was stable (p value: 0.61). In the four non-responders, the ADC increase was not significant (p value: 0.25), while it was significant in the 11 responders (p value: 0.001). Values of spectroscopy were stable in both responders and non-responders. CONCLUSIONS: High increases of ADC values from baseline to mid-therapy MR reflect response to therapies. There were no significant variations in choline/water ratios over time. PMID- 27372709 TI - Involving immigrant religious organizations in HIV/AIDS prevention: The role of bonding and bridging social capital. AB - Immigrant religious organizations in the United States are uniquely positioned to address critical issues beyond religion because of their moral, social and cultural prominence in community life. Increasingly, religious organizations have taken on a leadership role around health issues such as decreasing HIV/AIDS stigma and misinformation. However, there are barriers for some religious leaders and organizations in adopting new health programs, especially if the issue is seen as controversial. Our study examines how social network structures among religious members influence organizational acceptance of new information or controversial ideas, like HIV/AIDS. Using social network analysis methods on data from 2841 contacts in 20 immigrant Chinese Buddhist temples and Christian churches in New York City, we tested whether an immigrant religious organization's likelihood of being involved in HIV/AIDS activities was associated with the presence of bonding or bridging social capital. These two forms of social capital have been found to mediate the levels of exposure and openness to new ideas. We found HIV/AIDS-involved religious organizations were more likely to have lower levels of bonding social capital as indicated by members having fewer ties and fewer demographic attributes in common. We also found HIV/AIDS-involved religious organizations were more likely to have higher levels of bridging social capital as indicated by members having significantly more ties to people outside of their organization. Our study highlights the importance of looking beyond religion type and leadership attributes to social network structures among members in order to better explain organization-level receptiveness to HIV/AIDS involvement. PMID- 27372710 TI - Association between polymorphisms in genes related to DNA base-excision repair with risk and prognosis of oropharyngeal squamous cell carcinoma. AB - PURPOSE: We examined the influence of OGG1 c.977C>G (rs1052133), APEX1 c.444T>G (rs1130409), XRCC1 c.-77T>C (rs3213245), c.580C>T (rs1799782), c.839G>A (rs25489) and c.1196G>A (rs25487) single-nucleotide polymorphisms (SNPs), involved in base excision repair (BER) pathway, on oropharyngeal squamous cell carcinoma (OPSCC) risk and prognosis. METHODS: Aiming to identify the genotypes, DNA from 200 consecutive OPSCC patients and 200 controls was analyzed by PCR-RFLP. The prognostic impact of genotypes of SNPs on progression-free survival (PFS) and overall survival of OPSCC patients was examined using the Kaplan-Meier estimates and Cox regression analyses. RESULTS: XRCC1 c.580CT or TT genotypes (19.5 vs. 11.0 %, P = 0.04) and XRCC1 TTGG haplotype from c.-77T>C, c.580C>T, c.839G>A and c.1196G>A SNPs (17.5 vs. 10.0 %, P = 0.04) were more common in patients with OPSCC than in controls. Carriers of combined genotypes of c.580C>T and TTGG haplotype of XRCC1 gene were under 3.35- and 3.22-fold increased risk of OPSCC than others. For survival analysis, we selected only patients with tumor at stage IV. The median follow-up time was 24.5 months. At 24 months of follow-up, PFS was shorter in patients with OGG1 c.977CC genotype when compared with others genotypes (35.5 vs. 52.1 %, log-rank test, P = 0.03). After multivariate Cox analysis, patients with OGG1 c.977CC genotype had more chance to present tumor progression when compared with others (HR 1.68, P = 0.02). CONCLUSIONS: Our data present, for the first time, evidence that inherited OGG1 c.977C>G; XRCC1 c. 77T>C, c.580C>T, c.839G>A and c.1196G>A abnormalities of DNA BER pathway are important determinants of OPSCC and predictors of patient outcomes. PMID- 27372711 TI - An unusual, iatrogenic cause of massive airleak. PMID- 27372712 TI - Chloroplast avoidance movement as a sensitive indicator of relative water content during leaf desiccation in the dark. AB - In the context of global climate change, drought is one of the major stress factors with negative effect on photosynthesis and plant productivity. Currently, chlorophyll fluorescence parameters are widely used as indicators of plant stress, mainly owing to the rapid, non-destructive and simple measurements this technique allows. However, these parameters have been shown to have limited sensitivity for the monitoring of water deficit as leaf desiccation has relatively small effect on photosystem II photochemistry. In this study, we found that blue light-induced increase in leaf transmittance reflecting chloroplast avoidance movement was much more sensitive to a decrease in relative water content (RWC) than chlorophyll fluorescence parameters in dark-desiccating leaves of tobacco (Nicotiana tabacum L.) and barley (Hordeum vulgare L.). Whereas the inhibition of chloroplast avoidance movement was detectable in leaves even with a small RWC decrease, the chlorophyll fluorescence parameters (F V/F M, V J, F PSII, NPQ) changed markedly only when RWC dropped below 70 %. For this reason, we propose light-induced chloroplast avoidance movement as a sensitive indicator of the decrease in leaf RWC. As our measurement of chloroplast movement using collimated transmittance is simple and non-destructive, it may be more suitable in some cases for the detection of plant stresses including water deficit than the conventionally used chlorophyll fluorescence methods. PMID- 27372713 TI - Externalizing religious health beliefs and health and well-being outcomes. AB - Certain religious beliefs related to perceptions of internal or external health control (including belief in the existence of miraculous healing, and beliefs deferring responsibility for health outcomes from the self and onto God) may be related to health behaviors and in turn to health outcomes. Using data from a nationally representative US survey of religion and health (N = 2948) this study evaluates a series of two structural equation models of the relationships between religious activity, externalizing religious health beliefs (belief in healing miracles and divine health deferral), health outcomes, and life satisfaction. Believing in healing miracles was related to greater divine health deferral. Greater divine health deferral was associated with poorer symptoms of physical health. Belief in miracles was related to greater life satisfaction. Comparison of coefficients across models indicated that externalizing beliefs had a significant suppressor effect on the relationship between religious activity and physical symptoms, but did not significantly mediate its relationship with life satisfaction. Religious beliefs emphasizing divine control over health outcomes may have negative consequences for health outcomes, although the same beliefs may contribute to a better sense of life satisfaction. PMID- 27372714 TI - The role of appraisal and coping style in relation with societal participation in fatigued patients with multiple sclerosis: a cross-sectional multiple mediator analysis. AB - To determine the relationship between appraisal and societal participation in fatigued patients with Multiple Sclerosis (MS), and whether this relation is mediated by coping styles. 265 severely-fatigued MS patients. Appraisal, a latent construct, was created from the General Self-Efficacy Scale and the helplessness and acceptance subscales of the Illness Cognition Questionnaire. Coping styles were assessed using the Coping Inventory Stressful Situations (CISS21) and societal participation was assessed using the Impact on Participation and Autonomy. A multiple mediator model was developed and tested by structural equation modeling on cross-sectional data. We corrected for confounding by disease-related factors. Mediation was determined using a product-of-coefficients approach. A significant relationship existed between appraisal and participation (beta = 0.21, 95 % CI 0.04-0.39). The pathways via coping styles were not significant. In patients with severe MS-related fatigue, appraisal and societal participation show a positive relationship that is not mediated by coping styles. PMID- 27372715 TI - Metabolic fate of desomorphine elucidated using rat urine, pooled human liver preparations, and human hepatocyte cultures as well as its detectability using standard urine screening approaches. AB - Desomorphine is an opioid misused as "crocodile", a cheaper alternative to heroin. It is a crude synthesis product homemade from codeine with toxic byproducts. The aim of the present work was to investigate the metabolic fate of desomorphine in vivo using rat urine and in vitro using pooled human liver microsomes and cytosol as well as human liver cell lines (HepG2 and HepaRG) by Orbitrap-based liquid chromatography-high resolution-tandem mass spectrometry or hydrophilic interaction liquid chromatography. According to the identified metabolites, the following metabolic steps could be proposed: N-demethylation, hydroxylation at various positions, N-oxidation, glucuronidation, and sulfation. The cytochrome P450 (CYP) initial activity screening revealed CYP3A4 to be the only CYP involved in all phase I steps. UDP-glucuronyltransferase (UGT) initial activity screening showed that UGT1A1, UGT1A8, UGT1A9, UGT1A10, UGT2B4, UGT2B7, UGT2B15, and UGT2B17 formed desomorphine glucuronide. Among the tested in vitro models, HepaRG cells were identified to be the most suitable tool for prediction of human hepatic phase I and II metabolism of drugs of abuse. Finally, desomorphine (crocodile) consumption should be detectable by all standard urine screening approaches mainly via the parent compound and/or its glucuronide assuming similar kinetics in rats and humans. PMID- 27372716 TI - Monitoring antigenic protein integrity during glycoconjugate vaccine synthesis using capillary electrophoresis-mass spectrometry. AB - A capillary electrophoresis-mass spectrometry (CE-MS) method was developed for the characterization and integrity assessment of the Mycobacterium tuberculosis (MTB) antigens TB10.4 and Ag85B and their chemically produced glycoconjugates, which are glycovaccine candidates against tuberculosis (TB). In order to prevent protein adsorption to the inner capillary wall and to achieve efficient separation of the antigen proteoforms, a polyionic multilayer coating of polybrene-dextran sulfate-polybrene (PB-DS-PB) was used in combination with 1.5 M acetic acid as background electrolyte (BGE). Coupling of CE to high-resolution time-of-flight MS was achieved by a coaxial interface employing a sheath liquid of isopropanol-water (50:50, v/v) containing 0.1 % formic acid. The MTB antigens were exposed to experimental conditions used for chemical glycosylation (but no activated saccharide was added) in order to investigate their stability during glycovaccine production. CE-MS analysis revealed the presence of several closely related degradation products, including truncated, oxidized and conformational variants, which were assigned by accurate mass. Analysis of synthesized mannose conjugates of TB10.4 and Ag85B allowed the determination of the glycoform composition of the neo-glycoproteins next to the characterization of degradation products which were shown to be partly glycoconjugated. Moreover, the selectivity of CE-MS allowed specific detection of deamidated species (protein mass change of 1.0 Da only), indicating that chemical glycosylation increased susceptibility to deamidation. Overall, the results show that CE-MS represents a useful analytical tool for the detailed characterization and optimization of neo-glycoconjugate products. Graphical Abstract Flowchart illustrating Mycobacterium tuberculosis (MTB) antigen glycosylation, glycoconjugate variant and degradation product separation by capillary electrophoresis (CE) and their characterization by intact mass spectrometry (MS). PMID- 27372717 TI - Unusual stacking with electrokinetic injection of cationic analytes from micellar solutions in capillary zone electrophoresis. AB - Electrokinetic injection (EKI) in capillary zone electrophoresis (CZE) of charged analytes is by the electroosmotic flow (EOF) and electrophoretic mobility of analytes. In most forms of stacking with EKI, the sample ions were introduced via electrophoretic mobility and concentrated in a stacking boundary inside the capillary. In this work, we describe the unusual stacking of cationic analytes via EKI of sodium dodecyl sulfate (SDS) micelles into a fused silica capillary filled with acidic background solution (BGS) with 40-50 % acetonitrile. The analytes prepared with SDS micelles were injected because of their interaction with micelles or effective electrophoretic mobility. We observed two peaks from an analyte, and this suggested the concentration of analytes into two stacking zones. These two adjacent stacking zones were surprisingly maintained inside the capillary during EKI although the EOF was moving towards the inlet. The zones were identified as the SDS micelles (micelles zone) and organic solvent-rich stacking zone (solvent-rich zone) where the micelles zone was closer to the inlet end of capillary. The analytes concentrated in the solvent-rich zone through the mechanism of micelle to solvent stacking (MSS). The concentrated analytes in the micelles zone were from the concentrated analytes that electrophoretically migrated into the micelles zone from the solvent-rich zone during EKI. The analytes in the micelles zone were then re-stacked by MSS and formed the second sharp peak in CZE. This was prevented by reduction of acetonitrile concentration in the inlet BGS. A sensitivity enhancement factor of more than 100 was obtained for model cationic drugs (diphenhydramine and imipramine). PMID- 27372718 TI - Ultrasound assisted extraction combined with dispersive liquid-liquid microextraction (US-DLLME)-a fast new approach to measure phthalate metabolites in nails. AB - A new, fast, and environmentally friendly method based on ultrasound assisted extraction combined with dispersive liquid-liquid microextraction (US-DLLME) was developed and optimized for assessing the levels of seven phthalate metabolites (including the mono(ethyl hexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5-OH-MEHP), mono(2-ethyl-5-oxohexyl) phthalate (5-oxo-MEHP), mono-n butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monoethyl phthalate (MEP), and mono-benzyl phthalate (MBzP)) in human nails by UPLC-MS/MS. The optimization of the US-DLLME method was performed using a Taguchi combinatorial design (L9 array). Several parameters such as extraction solvent, solvent volume, extraction time, acid, acid concentration, and vortex time were studied. The optimal extraction conditions achieved were 180 MUL of trichloroethylene (extraction solvent), 2 mL trifluoroacetic acid in methanol (2 M), 2 h extraction and 3 min vortex time. The optimized method had a good precision (6-17 %). The accuracy ranged from 79 to 108 % and the limit of method quantification (LOQm) was below 14 ng/g for all compounds. The developed US-DLLME method was applied to determine the target metabolites in 10 Belgian individuals. Levels of the analytes measured in nails ranged between <12 and 7982 ng/g. The MEHP, MBP isomers, and MEP were the major metabolites and detected in every sample. Miniaturization (low volumes of organic solvents used), low costs, speed, and simplicity are the main advantages of this US-DLLME based method. Graphical Abstract Extraction and phase separation of the US-DLLME procedure. PMID- 27372719 TI - Conducting Fibers: Downsized Sheath-Core Conducting Fibers for Weavable Superelastic Wires, Biosensors, Supercapacitors, and Strain Sensors (Adv. Mater. 25/2016). AB - Using intelligent textiles for clothing represents one possibility for weavable superelastic conducting fibers that can store energy, sense body motions, and detect biochemicals. On page 4998, S. Yin, R. H. Baughman, and co-workers demonstrate that these hair-like-diameter fibers, comprising buckled carbon nanotube sheaths on a rubber core, can be used as glucose sensors, supercapacitors, ultrafast strain sensors, and electrical interconnectors. The performance of these structures is maintained also under giant strain. PMID- 27372721 TI - Atomic Layers: Tellurium-Assisted Epitaxial Growth of Large-Area, Highly Crystalline ReS2 Atomic Layers on Mica Substrate (Adv. Mater. 25/2016). AB - H. Xu, J. Zhang, and co-workers synthesize anisotropic 2D-layered rhenium disulfide with high crystal quality and uniform monolayer thickness. As described on page 5019, tellurium-assisted epitaxial growth on a mica substrate is chosen to generate such structures. PMID- 27372722 TI - Gallium Adhesion: Phase Change of Gallium Enables Highly Reversible and Switchable Adhesion (Adv. Mater. 25/2016). AB - M. Sitti and co-workers find that gallium exhibits highly reversible and switchable adhesive characteristics during the liquid-solid phase change. As described on page 5088, this reversible adhesive allows miniature capsule-like robots, which are able to easily pick-and-place objects with irregular geometries and rough surfaces, and thus assemble such objects into a complex structure. The contact interface between gallium and the rough object is illustrated in the magnified image. PMID- 27372723 TI - Ferromagnetism: Sulfur Doping Induces Strong Ferromagnetic Ordering in Graphene: Effect of Concentration and Substitution Mechanism (Adv. Mater. 25/2016). AB - R. Zboril and co-workers show that doping a graphene lattice with sulfur induces magnetic centers which display ferromagnetic order below ~62 K. As described on page 5045, sulfur doping promotes magnetically active configurations resembling the gamma-thiothiapyrone motif. Enhanced magnetic properties of sulfur-doped graphene are attributed to two unpaired electrons from each sulfur atom injected into the graphene conducting band where they are delocalized between the S and C atoms. PMID- 27372724 TI - Carbon Nanosheets: Nitrogen-Doped Porous Carbon Nanosheets Templated from g-C3 N4 as Metal-Free Electrocatalysts for Efficient Oxygen Reduction Reaction (Adv. Mater. 25/2016). AB - T. Zhang and co-workers report the synthesis of nitrogen-doped porous carbon nanosheets with extremely high nitrogen content and high surface areas using graphitic carbon nitride (g-C3 N4 ) as template, nitrogen source, and porogen. As described on page 5080, the nanosheets exhibit outstanding oxygen reduction catalytic activities which are comparable to commercial Pt/C catalysts in alkaline media. PMID- 27372726 TI - Mailed specimen collection for HIV testing in regional Queensland, Australia: a second attempt. PMID- 27372727 TI - Calcified left ventricular noncompaction with complete atrioventricular block. PMID- 27372728 TI - [Not Available]. AB - The aim of this study was to identify, in (pre-) clinically obtained data, parameters predicting the outcome of patients with multiple trauma and severe head injury. Fifty-eight patients aged 27+/-10 years were investigated an average of 5.8 years after the accident. The Hanover Polytrauma Score was 34+/-11 points, the initially assessed Glasgow Coma Scale (GCS) was 6.2+/-3.2 points; and the duration of coma was 15.4+/-14.4 days. The primary length of stay in hospital averaged 33.4 days, including 22.9 days in the intensive care unit and 20.2 days of ventilation. For a further 223 days the patients were treated at the Neurologic Clinic of Hessisch Oldendorf. Besides different neurologic deficiency symptoms, the psychometric tests showed deficits in all areas. In particular, information processing speed, concentration, recent memory and learning performance were impaired. There was free mobility of all joints in 33% of the patients. Due to injury the elbow and ankle joint developed the worst restriction. Central paralysis and heterotopic ossification also caused a restriction in joint mobility. Half of the patients were confronted with different social changes. The rate of return to work was dependent on age. Some 42% of all patients had taken up their former profession, 5% were still in training or at college, 32% were retrained to other professions, 16% were unemployed and 5% were completely retired on pension. Age, injury severity, GCS, duration of coma and duration of weaning were suitable predictors in correlation- and regression analysis. The Glasgow Outcome Scale showed good recovery and moderate disability in 53%, severe disability in 33% and persistent vegetative state in 14% of the patients. PMID- 27372729 TI - Cardiac and Circulatory Load When Playing Golf: Normal Subjects versus Patients with Coronary Heart Disease. PMID- 27372730 TI - Comparative proteomic analysis of the response to silver ions and yeast extract in Salvia miltiorrhiza hairy root cultures. AB - Biotic and abiotic stresses can inhibit plant growth, resulting in losses of crop productivity. However, moderate adverse stress can promote the accumulation of valuable natural products in medicinal plants. Elucidating the underlying molecular mechanisms thus might help optimize the variety of available plant medicinal materials and improve their quality. In this study, Salvia miltiorrhiza hairy root cultures were employed as an in vitro model of the Chinese herb Danshen. A comparative proteomic analysis using 2-dimensional gel electrophoresis and MALDI-TOF-MS was performed. By comparing the gel images of groups exposed to the stress of yeast extract (YE) combined with Ag(+) and controls, 64 proteins were identified that showed significant changes in protein abundance for at least one time point after treatment. According to analysis based on the KEGG and related physiological experimental verification, it was found that YE and Ag(+) stress induced a burst of reactive oxygen species and activated the Ca(2+)/calmodulin signaling pathway. Expression of immune-suppressive proteins increased. Epidermal cells underwent programmed cell death. Energy metabolism was enhanced and carbon metabolism shifted to favor the production of secondary metabolites such as lignin, tanshinone and salvianolic acids. The tanshinone and salvianolic acids were deposited on the collapsed epidermal cells forming a physicochemical barrier. The defense proteins and these natural products together enhanced the stress resistance of the plants. Since higher levels of natural products represent good quality in medicinal materials, this study sheds new light on quality formation mechanisms of medicinal plants and will hopefully encourage further research on how the planting environment affects the efficacy of herbal medicines. PMID- 27372731 TI - Chimeric antigen receptors: driving immunology towards synthetic biology. AB - The advent of second generation chimeric antigen receptors and the CD19 paradigm have ushered a new therapeutic modality in oncology. In contrast to earlier forms of adoptive cell therapy, which were based on the isolation and expansion of naturally occurring T cells, CAR therapy is based on the design and manufacture of engineered T cells with optimized properties. A new armamentarium, comprising not only CARs but also chimeric costimulatory receptors, chimeric cytokine receptors, inhibitory receptors and synthetic Notch receptors, expressed in naive, central memory or stem cell-like memory T cells, is being developed for clinical use in a wide range of cancers. Immunological principles are thus finding a new purpose thanks to advances in genetic engineering, synthetic biology and cell manufacturing sciences. PMID- 27372732 TI - High-throughput genomic profiling of tumor-infiltrating leukocytes. AB - Tumors are complex ecosystems comprised of diverse cell types including malignant cells, mesenchymal cells, and tumor-infiltrating leukocytes (TILs). While TILs are well known to play important roles in many aspects of cancer biology, recent developments in immuno-oncology have spurred considerable interest in TILs, particularly in relation to their optimal engagement by emerging immunotherapies. Traditionally, the enumeration of TIL phenotypic diversity and composition in solid tumors has relied on resolving single cells by flow cytometry and immunohistochemical methods. However, advances in genome-wide technologies and computational methods are now allowing TILs to be profiled with increasingly high resolution and accuracy directly from RNA mixtures of bulk tumor samples. In this review, we highlight recent progress in the development of in silico tumor dissection methods, and illustrate examples of how these strategies can be applied to characterize TILs in human tumors to facilitate personalized cancer therapy. PMID- 27372733 TI - Bimodality of Latitudinal Gradients in Marine Species Richness. AB - The paradigm for the latitudinal gradient in species richness is that it is unimodal with a tropical peak. For 27 published studies, and global datasets of 65 000 recent and 50 000 fossil marine species, we found that almost all datasets were significantly bimodal with a dip in species richness near the equator. The locations of mid-latitude peaks varied between taxa and were higher in the northern hemisphere where the continental shelf is greatest. Our findings support hypotheses of tropical species evolving in response to temperature variation near the edges of the tropics and available high-productivity habitat. They suggest that the equator may already be too hot for some species and that the modes may move further apart due to climate warming. PMID- 27372734 TI - Comparison of the anogenital distance and anthropometry of the perineum in patients with and without pelvic organ prolapse. AB - OBJECTIVES: To determine whether there are differences in the anthropometric measures of the perineum for women with symptomatic pelvic organ prolapse who are candidates for surgery, with or without urinary incontinence, and for patients without pelvic floor dysfunction. The main objective was to measure the anogenital distance in its 2 variants: anoclitoral and anofourchette. The anogenital distance appears to be determined prenatally and is influenced by the intrauterine hormonal environment. The secondary objective was to measure the length of the genital hiatus, the perineal body and the distance between the 2 ischial tuberosities. MATERIAL AND METHODS: An observational case-control study was conducted with 58 patients. The cases (n=22) were patients with stages >II 2 in the Baden-Walker classification system. The controls were patients with normal pelvic floors. Measurements were performed with a digital calliper. The patients' tocogynecological history, lifestyle habits and risk factors were recorded. RESULTS: The case patients had a significantly shorter anogenital anofourchette distance than that of the control patients (P=.001), a significantly longer anogenital anoclitoral distance than the control patients (P=.0001) and a significantly longer genital hiatus length than the control patients (P=.02). CONCLUSIONS: This was an observational study with a small sample. We cannot determine whether the difference in these distances are caused by or are the result of this disease. Given that the anogenital distance appears to be determined prenatally, we question whether this changed distance could be a risk factor for developing pelvic floor dysfunction. PMID- 27372735 TI - Aminosalicylates for induction of remission or response in Crohn's disease. AB - BACKGROUND: Randomized trials investigating the efficacy of aminosalicylates for the treatment of mildly to moderately active Crohn's disease have yielded conflicting results. A systematic review was conducted to critically examine current available data on the efficacy of sulfasalazine and mesalamine for inducing remission or clinical response in these patients. OBJECTIVES: To evaluate the efficacy of aminosalicylates compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) for the treatment of mildly to moderately active Crohn's disease. SEARCH METHODS: We searched PubMed, EMBASE, MEDLINE and the Cochrane Central Library from inception to June 2015 to identify relevant studies. There were no language restrictions. We also searched reference lists from potentially relevant papers and review articles, as well as proceedings from annual meetings (1991-2015) of the American Gastroenterological Association and American College of Gastroenterology. SELECTION CRITERIA: Randomized controlled trials that evaluated the efficacy of sulfasalazine or mesalamine in the treatment of mildly to moderately active Crohn's disease compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) were included. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of methodological quality was independently performed by the investigators and any disagreement was resolved by discussion and consensus. We assessed methodological quality using the Cochrane risk of bias tool. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. The primary outcome measure was a well defined clinical endpoint of induction of remission or response to treatment. Secondary outcomes included mean Crohn's disease activity index (CDAI) scores, adverse events, serious adverse events and withdrawal due to adverse events. For dichotomous outcomes we calculated the pooled risk ratio (RR) and corresponding 95% confidence interval (CI) using a random-effects model. For continuous outcomes we calculated the mean difference (MD) and 95% CI using a random-effects model. Sensitivity analyses based on a fixed-effect model and duration of therapy were conducted where appropriate. MAIN RESULTS: Twenty studies (2367 patients) were included. Two studies were judged to be at high risk of bias due to lack of blinding. Eight studies were judged to be at high risk of bias due to incomplete outcomes data (high drop-out rates) and potential selective reporting. The other 10 studies were judged to be at low risk of bias. A non-significant trend in favour of sulfasalazine over placebo for inducing remission was observed, with benefit confined mainly to patients with Crohn's colitis. Forty-five per cent (63/141) of sulfasalazine patients entered remission at 17-18 weeks compared to 29% (43/148) of placebo patients (RR 1.38, 95% CI 1.00 to 1.89, 2 studies). A GRADE analysis rated the overall quality of the evidence supporting this outcome as moderate due to sparse data (106 events). There was no difference between sulfasalazine and placebo in adverse event outcomes. Sulfasalazine was significantly less effective than corticosteroids and inferior to combination therapy with corticosteroids (RR 0.64, 95% CI 0.47 to 0.86, 1 study, 110 patients). Forty-three per cent (55/128) of sulfasalazine patients entered remission at 17 to 18 weeks compared to 60% (79/132) of corticosteroid patients (RR 0.68, 95% CI 0.51 to 0.91; 2 studies, 260 patients). A GRADE analysis rated the overall quality of the evidence supporting this outcome as moderate due to sparse data (134 events). Sulfasalazine patients experienced significantly fewer adverse events than corticosteroid patients (RR 0.43, 95% CI 0.22 to 0.82; 1 study, 159 patients). There was no difference between sulfasalazine and corticosteroids in serious adverse events or withdrawal due to adverse events. Olsalazine was less effective than placebo in a single trial (RR 0.36, 95% CI 0.18 to 0.71; 91 patients). Low dose mesalamine (1 to 2 g/day) was not superior to placebo for induction of remission. Twenty-three per cent (43/185) of low dose mesalamine patients entered remission at week 6 compared to 15% (18/117) of placebo patients (RR = 1.46, 95% CI 0.89 to 2.40; n = 302). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to risk of bias (incomplete outcome data) and sparse data (61 events). There was no difference between low dose mesalamine and placebo in the proportion of patients who had adverse events (RR 1.33, 95% CI 0.91 to 1.96; 3 studies, 342 patients) or withdrew due to adverse events (RR 1.21, 95% CI 0.75 to 1.95; 3 studies, 342 patients). High dose controlled-release mesalamine (4 g/day) was not superior to placebo, inducing a clinically non significant reduction in CDAI (MD 19.8 points, 95% CI -46.2 to 6.7; 3 studies, 615 patients), and was also inferior to budesonide (RR 0.56, 95% CI 0.40 to 0.78; 1 study, 182 patients, GRADE = low). While high dose delayed-release mesalamine (3 to 4.5 g/day) was not superior to placebo for induction of remission (RR 2.02, 95% CI 0.75 to 5.45; 1 study, 38 patients, GRADE = very low), no significant difference in efficacy was found when compared to conventional corticosteroids (RR 1.04, 95% CI 0.79 to 1.36; 3 studies, 178 patients, GRADE = moderate) or budesonide (RR 0.89, 95% CI 0.76 to 1.05; 1 study, 307 patients, GRADE = moderate). However, these trials were limited by risk of bias (incomplete outcome data) and sparse data (small numbers of events). There was a lack of good quality clinical trials comparing sulfasalazine with other mesalamine formulations. Adverse events that were commonly reported included headache, nausea, vomiting, abdominal pain and diarrhea. AUTHORS' CONCLUSIONS: Sulfasalazine is only modestly effective with a trend towards benefit over placebo and is inferior to corticosteroids for the treatment of mildly to moderately active Crohn's disease. Olsalazine and low dose mesalamine (1 to 2 g/day) are not superior to placebo. High dose mesalamine (3.2 to 4 g/day) is not more effective than placebo for inducing response or remission. However, trials assessing the efficacy of high dose mesalamine (4 to 4.5 g/day) compared to budesonide yielded conflicting results and firm conclusions cannot be made. Future large randomized controlled trials are needed to provide definitive evidence on the efficacy of aminosalicylates in active Crohn's disease. PMID- 27372736 TI - Hazardous waste management system design under population and environmental impact considerations. AB - This paper presents a multi objective mixed integer location/routing model that aims to minimize transportation cost and risks for large-scale hazardous waste management systems (HWMSs). Risks induced by hazardous wastes (HWs) on both public and the environment are addressed. For this purpose, a new environmental impact definition is proposed that considers the environmentally vulnerable elements including water bodies, agricultural areas, coastal regions and forestlands located within a certain bandwidth around transportation routes. The solution procedure yields to Pareto optimal curve for two conflicting objectives. The conceptual model developed prior to mathematical formulation addresses waste to-technology compatibility and HW processing residues to assure applicability of the model to real-life HWMSs. The suggested model was used in a case study targeting HWMS in Turkey. Based on the proposed solution, it was possible to identify not only the transportation routes but also a set of information on HW handling facilities including the types, locations, capacities, and investment/operational cost. The HWMS of this study can be utilized both by public authorities and private sector investors for planning purposes. PMID- 27372737 TI - A tale of two rain gardens: Barriers and bridges to adaptive management of urban stormwater in Cleveland, Ohio. AB - Green infrastructure installations such as rain gardens and bioswales are increasingly regarded as viable tools to mitigate stormwater runoff at the parcel level. The use of adaptive management to implement and monitor green infrastructure projects as experimental attempts to manage stormwater has not been adequately explored as a way to optimize green infrastructure performance or increase social and political acceptance. Efforts to improve stormwater management through green infrastructure suffer from the complexity of overlapping jurisdictional boundaries, as well as interacting social and political forces that dictate the flow, consumption, conservation and disposal of urban wastewater flows. Within this urban milieu, adaptive management-rigorous experimentation applied as policy-can inform new wastewater management techniques such as the implementation of green infrastructure projects. In this article, we present a narrative of scientists and practitioners working together to apply an adaptive management approach to green infrastructure implementation for stormwater management in Cleveland, Ohio. In Cleveland, contextual legal requirements and environmental factors created an opportunity for government researchers, stormwater managers and community organizers to engage in the development of two distinct sets of rain gardens, each borne of unique social, economic and environmental processes. In this article we analyze social and political barriers to applying adaptive management as a framework for implementing green infrastructure experiments as policy. We conclude with a series of lessons learned and a reflection on the prospects for adaptive management to facilitate green infrastructure implementation for improved stormwater management. PMID- 27372739 TI - Transradial versus transfemoral access for female patients who underwent primary PCI in STEMI: Two years follow-up data from acute STEMI interventional registry. AB - BACKGROUND: Female patients possess a higher risk for poorer outcome in ST segment elevation myocardial infarction (STEMI). There is possibility that transradial access (TRA) for primary percutaneous coronary intervention (PPCI) could provide better outcome than transfemoral access (TFA) in female patients with STEMI. METHODS: From 2008 to 2010, 418 female patients (out of 1808 patients) underwent PPCI for acute STEMI. The registry recruited all-comers patients with acute STEMI. Cardiac mortality, major bleeding, and overall MACE rates (composite of death, stroke, re MI and target vessel revascularization-TVR) after 2years follow-up were compared between TRA and TFA. RESULTS: TRA for PPCI was performed in 261 patients and 157 underwent TFA PPCI. The 30-days, 1year mortality and 2year mortality rates were lower in TRA compared to TFA (6.9% vs.14.6%, p=0.012, 8.8% vs. 15.3%, p=0.045, and 9.2% vs. 16.6%, p=0.027respectively). After 2years follow-up, the overall MACE rates were similar (26.4% vs. 31.2%, p=0.336). The overall major bleeding and major vascular access site bleeding were more favorable for TRA than TFA (4.4 vs. 14%, p<0.001, and 2.7 vs. 10.8%, p<0.001, respectively). CONCLUSION: Transradial access for primary PCI in female patients provided better clinical outcomes with lower cardiac mortality and reduced major bleeding in comparison to TFA. There was no significant difference at 2years MACE between TRA and TFA. PMID- 27372740 TI - Current uses of ISACS-TC registry in Mostar. AB - Cardiovascular disease (CVD) contributes greatly to inequalities in health in Europe. The acute myocardial infarction (MI) in hospital death rate in Bosnia and Herzegovina is three fold higher than in European Union countries before the enlargement in 2004. There is also a striking difference in mortality between Bosnia and Herzegovina and Central and East European countries that joined the EU in 2004. Rapid development of high technology treatment procedures, which followed the economic recovery of the European Union countries, still have only limited influence on the overall control of MI death rate. Large potential to control MI death rate lies in developing PCI capable network with target to rapid reperfusion therapy in MI patients. The hypothesis that social factors may contribute to explain high MI death rate is attractive, but still is an assumption. However, if confirmed, transforming such knowledge into a practical health policy would be a great challenge. A resource-saving balanced assessment approach to health technology development is warrant in Bosnia and Herzegovina. An international help is needed. PMID- 27372738 TI - Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer. AB - To provide a detailed analysis of the molecular components and underlying mechanisms associated with ovarian cancer, we performed a comprehensive mass spectrometry-based proteomic characterization of 174 ovarian tumors previously analyzed by The Cancer Genome Atlas (TCGA), of which 169 were high-grade serous carcinomas (HGSCs). Integrating our proteomic measurements with the genomic data yielded a number of insights into disease, such as how different copy-number alternations influence the proteome, the proteins associated with chromosomal instability, the sets of signaling pathways that diverse genome rearrangements converge on, and the ones most associated with short overall survival. Specific protein acetylations associated with homologous recombination deficiency suggest a potential means for stratifying patients for therapy. In addition to providing a valuable resource, these findings provide a view of how the somatic genome drives the cancer proteome and associations between protein and post translational modification levels and clinical outcomes in HGSC. VIDEO ABSTRACT. PMID- 27372741 TI - Carbon Catabolite Regulation of Secondary Metabolite Formation and Morphological Differentiation in Streptomyces coelicolor. AB - In the genus Streptomyces, carbon utilization is of significant importance for the expression of genes involved in morphological differentiation and antibiotic production. However, there is little information about the mechanism involved in these effects. In the present work, it was found that glucose exerted a suppressive effect on the Streptomyces coelicolor actinorhodin (Act) and undecylprodigiosin (Red) production, as well as in its morphological differentiation. Accordingly, using a high-density microarray approach in S. coelicolor grown under glucose repression, at early growth stages, a negative effect was exerted on the transcription of genes involved in Act and Red production, when compared with non-repressive conditions. Seven genes of Act and at least ten genes of Red production were down-regulated by glucose. Stronger repression was observed on the initial steps of antibiotics formation. On the contrary, the coelimycin P1 cluster was up-regulated by glucose. Regarding differentiation, no sporulation was observed in the presence of glucose and expression of a set of genes of the bld cascade was repressed as well as chaplins and rodlins genes. Finally, a series of transcriptional regulators involved in both processes were up- or down-regulated by glucose. This is the first global transcriptomic approach performed to understand the molecular basis of the glucose effect on the synthesis of secondary metabolism and differentiation in the genus Streptomyces. The results of this study are opening new avenues for further exploration. PMID- 27372742 TI - Caffeine ingestion improves power output decrement during 3-min all-out exercise. AB - PURPOSE: To investigate the effect of caffeine ingestion on the 3-min all-out test (3MT) performance and plasma electrolytes in athletes. METHODS: Fifteen collegiate male basketball players were recruited and completed two trials separated by at least 1 week in caffeine (CAF, 6 mg kg(-1)) and placebo conditions. During the first visit, participants performed an incremental cycling test to determine their 3MT resistance. After a familiarization trial, participants performed a CAF or PL trial according to a randomized crossover design. One hour after ingesting capsules, the participants performed the 3MT to estimate the end-test power (EP) and work done above EP (WEP). Blood samples for sodium (Na(+)), potassium (K(+)), pH, and lactate concentrations were drawn pretest, 1 h after ingestion, and posttest. RESULTS: Significant differences in WEP (CAF vs. PL, 13.4 +/- 3.0 vs. 12.1 +/- 2.7 kJ, P < 0.05) but not in EP (CAF vs. PL, 242 +/- 37 vs. 244 +/- 42 W, P > 0.05) were determined between the conditions. Compared with the PL condition, the CAF condition yielded significantly higher power outputs (60-150 s), a lower fatigue rate during the 3MT (CAF vs. PL, 0.024 +/- 0.007 vs. 0.029 +/- 0.006 s(-1), P < 0.05), a significantly higher lactate concentration after the 3MT, and significantly lower K(+) concentrations at 1 h after caffeine ingestion. There were no significant interaction effects for pH and Na(+) concentrations. CONCLUSIONS: Caffeine ingestion did not change EP but improved WEP and the rate of decline in power output during short-term, severe exercise. PMID- 27372743 TI - Association of green tea consumption with mortality from all-cause, cardiovascular disease and cancer in a Chinese cohort of 165,000 adult men. AB - Tea is the most ancient and popular beverage in the world, and its beneficial health effects has attracted tremendous attention worldwide. However, the prospective evidence relating green tea consumption to total and cause-specific mortality is still limited and inconclusive. We recruited 164,681 male participants free of pre-existing disease during 1990-1991, with green tea consumption and other covariates assessed by the standardized questionnaire and mortality follow up continued until 2006 (mean 11 years; total person-years: 1,961,791). Cox regression analyses were used to quantify the associations of green tea consumption with all-cause (n = 32,700), CVD (n = 11,839) and cancer (n = 7002) mortality, adjusting simultaneously for potential confounders. At baseline, 18 % reported regular consumption of green tea. Compared with non-green tea drinkers, regular drinkers had significantly lower all-cause mortality, with adjusted hazard ratios (HRs) being 0.94 (95 % CI 0.89, 0.99) for <=5 g/day, 0.95 (0.91, 0.99) for 5-10 g/day and 0.89 (0.85, 0.93) for >10 g/day. For CVD mortality, the corresponding HRs were 0.93 (0.85, 1.01) 0.91 (0.85, 0.98) and 0.86 (0.79, 0.93), respectively, while for cancer they were 0.86 (0.78, 0.98), 0.92 (0.83, 1.00) and 0.79 (0.71, 0.88), respectively. The patterns of these associations varied by smoking, alcohol drinking and locality. This large prospective study shows that regular green tea consumption is associated with significantly reduced risk of death from all-cause, CVD and cancer among Chinese adults. PMID- 27372744 TI - Introduction. PMID- 27372745 TI - Lymph node ratio predicts survival in hypopharyngeal cancer with positive lymph node metastasis. AB - The lymph node density (LND) has been reported to be a significant prognostic factor in various types of carcinoma. This study investigated whether the LND is associated with survival in patients with hypopharyngeal squamous cell carcinoma (HPSCC) who have positive lymph nodes without distant metastasis. Forty-six patients who were pathologically diagnosed with HPSCC with positive lymph nodes and without distant metastasis were enrolled in this study. The LND was defined as the ratio of positive lymph nodes to the total number of lymph nodes. An LND of >=0.09 was found to be significantly correlated with a shorter overall (p = 0.044) and disease-specific (p = 0.019) survival according to a log-rank test. In a multivariate survival analysis using a Cox proportional hazards model adjusted for the pathological T category (pT3-4/pT1-2), pathological N category (pN2/pN1) and positive surgical margin and/or extracapsular spread (presence/absence), both an LND of >=0.09 and pT3-4 category were associated with significantly shorter overall survival (p < 0.01) and disease-specific survival (p < 0.01). These results suggest that the LND functions as a prognostic factor for HPSCC patients with positive lymph nodes who do not have distant metastasis. PMID- 27372746 TI - Cone beam computed tomography (CBCT) as a tool for the analysis of nonhuman skeletal remains in a medico-legal setting. AB - To confirm the nature and forensic significance of questioned skeletal material submitted a medico-legal setting is a relatively common procedure, although not without difficulties when the remains are fragmented or burned. Different methodologies have been described for this purpose, many of them invasive, time and money consuming or dependent on the availability of the analytical instrument. We present a case in which skeletal material with unusual conditions of preservation and curious discovery was sent to a medico-legal setting to determine its human/nonhuman origin. A combined strategy of imagenological procedures (macroscopic, radiographic and cone beam computed tomography - CBCT technology) was performed as non-invasive and rapid methods to assess the nonhuman nature of the material, specifically of pig (Sus scrofa) origin. This hypothesis was later confirmed by DNA analysis. CBCT data sets provide accurate three-dimensional reconstructions, which demonstrate its reliable use as a forensic tool. PMID- 27372747 TI - In Vitro Chromatin Assembly: Strategies and Quality Control. AB - Chromatin accessibility is modulated by structural transitions that provide timely access to the genetic and epigenetic information during many essential nuclear processes. These transitions are orchestrated by regulatory proteins that coordinate intricate structural modifications and signaling pathways. In vitro reconstituted chromatin samples from defined components are instrumental in defining the mechanistic details of such processes. The bottleneck to appropriate in vitro analysis is the production of high quality, and quality-controlled, chromatin substrates. In this chapter, we describe methods for in vitro chromatin reconstitution and quality control. We highlight the strengths and weaknesses of various approaches and emphasize quality control steps that ensure reconstitution of a bona fide homogenous chromatin preparation. This is essential for optimal reproducibility and reliability of ensuing experiments using chromatin substrates. PMID- 27372748 TI - Preparation, Crystallization, and Structure Determination of Chromatin Enzyme/Nucleosome Complexes. AB - Structural studies of chromatin complexes composed of chromatin factors or enzymes bound to the nucleosome have been constrained by the ability to produce high-quality complexes in the amounts appropriate for biophysical studies and by the difficulty of crystallizing these complexes. We describe here procedures and approaches to prepare chromatin complexes, to crystallize chromatin complexes, and to improve diffraction properties through postcrystallization soaks. Special attention is paid to evaluating the quality of the purified chromatin complexes as well as assessing the presence of the chromatin protein or enzyme in crystals. The methods described for preparing and purifying chromatin complexes should be applicable to biochemical, biophysical, and other structural approaches including cryoelectron microscopy. PMID- 27372749 TI - Preparation of Recombinant Centromeric Nucleosomes and Formation of Complexes with Nonhistone Centromere Proteins. AB - Centromeres are present on each chromosome to direct proper segregation during cell division. The understanding of how the histone H3 variant, CENP-A, epigenetically marks the location of the centromere on the chromosome has been advanced, in part, through the study of histone complexes, nucleosomes, and nucleosomal complexes with nonhistone centromere proteins. In this chapter, we describe the preparation of recombinant versions of these complexes. The methodology is firmly rooted in classic nucleosome reconstitution methods, but we highlight the aspects of the preparations that diverge from those used for the methods established with canonical histones. We also provide a method for producing PCR-amplified nucleosomal DNA sequences in milligram quantities that is particularly useful for studies where multiple sequences and/or chemical modifications are desired. Lastly, we describe our approach to assemble and analyze a complex between the recombinant human CENP-A nucleosome and one of its binding partners, CENP-C. PMID- 27372750 TI - Functional Characterization of Histone Chaperones Using SNAP-Tag-Based Imaging to Assess De Novo Histone Deposition. AB - Histone chaperones-key actors in the dynamic organization of chromatin-interact with the various histone variants to ensure their transfer in and out of chromatin. In vitro chromatin assembly assays and isolation of protein complexes using tagged histone variants provided first clues concerning their binding specificities and mode of action. Here, we describe an in vivo method using SNAP tag-based imaging to assess the de novo deposition of histones and the role of histone chaperones. This method exploits cells expressing SNAP-tagged histones combined with individual cell imaging to visualize directly de novo histone deposition in vivo. We show how, by combining this method with siRNA-based depletion, we could assess the function of two distinct histone chaperones. For this, we provide the details of the method as applied in two examples to characterize the function of the histone chaperones CAF-1 and HIRA. In both cases, we document the impact of their depletion on the de novo deposition of the histone variants H3.1 and H3.3, first in a normal context and second in response to DNA damage. We discuss how this cellular assay offers means to define in a systematic manner the function of any chosen chaperone with respect to the deposition of a given histone variant. PMID- 27372751 TI - Analysis of Nucleosome Sliding by ATP-Dependent Chromatin Remodeling Enzymes. AB - ATP-dependent chromatin remodeling complexes carry out diverse transformations of chromatin. Understanding their mechanisms requires assays that can monitor the kinetics or chromatin remodeling. In this chapter, we describe complimentary native gel-based and FRET-based methods for assaying the kinetics of ATP-driven nucleosome sliding. These methods can be readily adapted to investigate other types of nucleosomal transformations carried out by chromatin remodeling ATPases. PMID- 27372753 TI - Preparation and Biochemical Analysis of Classical Histone Deacetylases. AB - Histone deacetylase assays were first developed in the 1970s, and subsequently refined in the 1990s with the cloning of HDAC enzymes. Most of these early assays, relying on traditional in vitro chemical methodologies, are still applicable today. More recently, however, cell-based HDAC assays that measure HDAC activities in physiological conditions are emerging. Also, there is a continuing development of assays that can measure an isolated HDAC in the absence of other HDAC activities. This chapter reviews some of the older established methods for assaying HDAC activities, as well as introduces more recently developed nontraditional assays. PMID- 27372752 TI - In Vitro Activity Assays for MYST Histone Acetyltransferases and Adaptation for High-Throughput Inhibitor Screening. AB - Lysine acetylation is a posttranslational modification that is carried out by acetyltransferases. The MYST proteins form the largest and most diverse family of acetyltransferases, which regulate gene expression, DNA repair, and cell cycle homeostasis, among other activities, by acetylating both histone and nonhistone proteins. This chapter will describe methods for the preparation and biochemical characterization of MYST family acetyltransferases, including protocols for the preparation of recombinant protein, enzyme assays for measuring steady-state parameters, and binding assays to measure cofactor and inhibitor binding. We also provide details on adapting these assays for high-throughput screening for small molecule MYST inhibitors. This chapter seeks to prepare researchers for some hurdles that they may encounter when studying the MYST proteins so that there may be better opportunity to plan appropriate controls and obtain high-quality data. PMID- 27372754 TI - Recombinant Preparation, Biochemical Analysis, and Structure Determination of Sirtuin Family Histone/Protein Deacylases. AB - Lysine acetylation is long known as a regulatory posttranslational modification of histone proteins and is emerging as a ubiquitous intracellular protein modification. Additional lysine acylations such as succinylation and glutarylation have also been found on histones and other proteins. Acylations are reversibly attached through nonenzymatic acylation mechanisms and the action of protein acyl transferases and protein deacylases (PDACs). Sirtuins are an evolutionary defined class of PDACs and act as metabolic sensors by catalyzing a unique deacylation reaction that requires the cosubstrate NAD(+). Sirtuins are found in all domains of life, and the mammalian sirtuin family comprises seven isoforms in different cellular compartments. They regulate a wide range of cellular targets and functions, such as energy metabolism and stress responses, and they have been implicated in aging processes and aging-related diseases. A large body of functional, biochemical, biophysical, and structural work on isolated sirtuins has provided many important insights that complement the many physiological studies on this enzyme family. They enabled the comprehensive structural and biochemical analysis of sirtuin catalysis, substrate selectivity, and regulation. Here, we describe the recombinant production of sirtuin proteins, with an emphasis on the mammalian isoforms. We then describe their application in activity and binding assays and for crystal structure analysis. We provide protocols for these procedures, and we discuss typical pitfalls in studying this enzyme family and how to avoid them. This information will support further molecular studies on sirtuin mechanisms and functions. PMID- 27372755 TI - Preparation, Biochemical Analysis, and Structure Determination of SET Domain Histone Methyltransferases. AB - In eukaryotes, several lysine residues on histone proteins are methylated. This posttranslational modification is linked to a myriad of nuclear-based transactions such as epigenetic inheritance of heterochromatin, regulation of gene expression, DNA damage repair, and DNA replication. The majority of the enzymes responsible for writing these marks onto chromatin belong to the SET domain family of histone lysine methyltransferases. Although they often share important structural features, including a conserved catalytic domain, SET domain enzymes use different mechanisms to achieve substrate recognition, mono-, di-, or trimethylate lysine residues and some require other proteins to achieve maximal methyltransferase activity. In this chapter, we summarize our efforts to purify, crystallize, and enzymatically characterize SET domain enzymes with a specific focus on the histone H3K27 monomethyltransferase ATXR5. PMID- 27372756 TI - Expression, Purification, and Biochemical Analysis of the LSD1/KDM1A Histone Demethylase. AB - Posttranslational modifications (PTMs) of histones play important roles in the regulation of chromatin architecture and gene transcription. A decade ago, it was still believed that methyl groups could not be removed from histones, until the first histone demethylase LSD1 (lysine-specific demethylase 1; also known as KDM1A) was identified. This discovery initiated an era in the understanding of chromatin dynamic regulation by active histone demethylation. Since then, the repertoire of histone demethylases has expanded, and our understanding of the molecular mechanisms, structures, and macromolecular complexes of the demethylases has grown significantly. Histone demethylases have emerged as important players in developmental processes and have been linked to human diseases and cancer. Studies highlighting the functions of LSD1 have significantly increased our understanding of chromatin biology and have revealed that new facets of histone demethylases remain to be discovered. In vitro methods have been developed to assess the biochemistry, structure, and enzymology of lysine demethylases. Here, we describe the methods of expression, purification, and biochemical analysis that we have successfully used in characterizing the functions of LSD1. PMID- 27372757 TI - LSD1 Histone Demethylase Assays and Inhibition. AB - The lysine-specific demethylase (LSD1) is a flavin-dependent amine oxidase that selectively removes one or two methyl groups from histone H3 at the Lys4 position. Along with histone deacetylases 1 and 2, LSD1 is involved in epigenetically silencing gene expression. LSD1 has been implicated as a potential therapeutic target in cancer and other diseases. In this chapter, we discuss several approaches to measure LSD1 demethylase activity and their relative strengths and limitations for inhibitor discovery and mechanistic characterization. In addition, we review the principal established chemical functional groups derived from monoamine oxidase inhibitors that have been investigated in the context of LSD1 as demethylase inhibitors. Finally, we highlight a few examples of recently developed LSD1 mechanism-based inactivators and their biomedical applications. PMID- 27372758 TI - Purification, Biochemical Analysis, and Structure Determination of JmjC Lysine Demethylases. AB - Jumonji C (JmjC) lysine demethylases (KDMs) catalyze the site- and state-specific demethylation of lysine residues in histone and nonhistone protein substrates. These enzymes have been implicated in diverse genomic processes, including epigenetic gene regulation, DNA damage response, DNA replication, and regulation of heterochromatin structure. In addition, a number of JmjC KDMs contribute to the incidence of numerous cancers, rendering them targets for the development of novel chemotherapeutic drugs. Using the JMJD2 KDM subfamily as representative examples, this chapter outlines strategies for purifying highly active, recombinant JmjC KDMs lacking inhibitory transition metal ions, characterizing kinetic parameters of these enzymes using a coupled fluorescent assay, and determining crystal structures of the enzymes in complex with methylated histone peptides. Together, these approaches provide a foundation for structural and biochemical characterization of the JmjC KDMs and facilitate efforts to identify small molecule inhibitors through high-throughput screening and structure-guided design. PMID- 27372759 TI - Preparation and Analysis of Native Chromatin-Modifying Complexes. AB - Nucleosomes, the basic units of chromatin, are decorated with a myriad of posttranslational modifications (PTMs) by the action of chromatin modifiers. These enzymes function almost exclusively as part of stable protein complexes that assist their recruitment to specific genomic loci, specify their substrate, and provide allosteric control. By altering the interactions within nucleosomes or with neighboring nucleosomes and serving as a platform to engage effector proteins, PTMs deposited by histone-modifying complexes influence virtually every nuclear process and are at the heart of the epigenetic mechanisms. Hence, it is critical to identify their components, define their structures, and characterize their biochemical activities. Here we describe protocols for tandem affinity purification (TAP) of native histone acetyltransferase (HAT) and methyltransferase (HMT) complexes from human cells engineered to express bait proteins from a genomic safe harbor or their endogenous chromosomal genes, using zinc-finger nucleases (ZFNs), TAL effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 systems. The approaches presented aim to preserve natural transcriptional and posttranscriptional regulation and minimize biochemical artifacts due to ectopic expression. Near homogenous preparations of native complexes are obtained in sufficient amounts to perform biochemical assays and characterize their components. PMID- 27372760 TI - Preparation, Biochemical Analysis, and Structure Determination of the Bromodomain, an Acetyl-Lysine Binding Domain. AB - The bromodomain (BrD) represents an evolutionarily conserved protein domain whose function mostly is to recognize acetylated lysine residues in histones and nuclear proteins in regulation of gene transcription in chromatin. The highly conserved BrD structure features an unusual left-handed, antiparallel four-helix bundle and a hydrophobic pocket between the interhelical ZA and BC loops important for acetyl-lysine binding. Many proteins, particularly transcriptional activators, contain BrDs, and mutation or deletion of the BrDs impairs the protein function, implying their critical role in human biology and disease. In this chapter, we provide general protocols of the preparation, biochemical analysis, and structure determination of BrDs, aiming to offer a general guideline for structural and biochemical functional characterization of BrD containing proteins. PMID- 27372761 TI - Preparation, Biochemical Analysis, and Structure Determination of Methyllysine Readers. AB - In-depth in vitro characterization of methyllysine reader domains and their association with cognate methyllysine substrates is essential to better understand fundamental mechanisms of chromatin regulation and to design targeted therapeutics that disrupt these interactions. In this chapter, we summarize commonly used methods for preparation, biochemical characterization, and determination of structures of methyllysine reader domains. We provide a detailed protocol for the preparation of a GST-tagged methyllysine reader domain and for analysis of histone-binding activities using a combination of pull-down, tryptophan fluorescence, and NMR assays, and describe initial steps toward crystallization of the complexes. PMID- 27372762 TI - Quantification of Oxidized 5-Methylcytosine Bases and TET Enzyme Activity. AB - In eukaryotic DNA, cytosine can be enzymatically modified to yield up to four epigenetic base variants. DNA methyltransferases convert cytosine to 5 methylcytosine (mC), which plays critical roles in gene regulation during development. Ten-eleven translocation (TET) enzymes can sequentially oxidize mC to three products: 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC), and 5 carboxylcytosine (caC). These oxidized bases have been found in numerous mammalian cell types, where they potentially carry out independent epigenetic functions and aid in DNA demethylation. To gain insight into the mechanisms and functions of TET family enzymes, rigorous approaches are needed to quantify genomic cytosine modifications in cells and track TET enzyme activity in vitro. Here, we present tools developed by our lab and others to report on each of the five forms of cytosine (unmodified, mC, hmC, fC, and caC) with high specificity and sensitivity. We provide detailed protocols for qualitative and quantitative analysis of cytosine modifications in genomic DNA by dot blotting and LC-MS/MS. We then describe methods for generating synthetic oligonucleotide substrates for biochemical studies, provide optimized reaction conditions, and introduce several chemoenzymatic assays, as well as HPLC, mass spectrometry, and scintillation counting methods to quantify cytosine modifications in vitro. These approaches enable mechanistic studies of TET activity, which are key to understanding the role of these enzymes in epigenetic regulation. PMID- 27372763 TI - Characterization of How DNA Modifications Affect DNA Binding by C2H2 Zinc Finger Proteins. AB - Much is known about vertebrate DNA methylation and oxidation; however, much less is known about how modified cytosine residues within particular sequences are recognized. Among the known methylated DNA-binding domains, the Cys2-His2 zinc finger (ZnF) protein superfamily is the largest with hundreds of members, each containing tandem ZnFs ranging from 3 to >30 fingers. We have begun to biochemically and structurally characterize these ZnFs not only on their sequence specificity but also on their sensitivity to various DNA modifications. Rather than following published methods of refolding insoluble ZnF arrays, we have expressed and purified soluble forms of ZnFs, ranging in size from a tandem array of two to six ZnFs, from seven different proteins. We also describe a fluorescence polarization assay to measure ZnFs affinity with oligonucleotides containing various modifications and our approaches for cocrystallization of ZnFs with oligonucleotides. PMID- 27372764 TI - Crystallographic Studies of Telomerase. AB - Telomeres are nucleoprotein complexes that maintain the ends of our chromosomes thus providing genomic stability. Telomerase is a ribonucleoprotein reverse transcriptase that replicates the short tandem repeats of DNA known as telomeres. The telomeric DNA is specifically associated with two major complexes, the shelterin and CST complexes both of which are involved in telomere length regulation and maintenance along with telomerase. Obtaining structural information on these nucleoprotein complexes has been a major bottleneck in fully understanding the mechanism of action of telomeric nucleoproteins for over two decades. The recent advances in molecular and structural biology have enabled us to obtain atomic resolution structures of telomeric proteins alone and in complex with their nucleic acid substrates transforming the field and our understanding and interpretation of this unique biological pathway. Here we report our approach to obtain the structure of the Triobolium castaneum catalytic subunit of telomerase TERT (tcTERT) in its apo- and substrate-bound states. PMID- 27372765 TI - Detection and Analysis of Long Noncoding RNAs. AB - Recent genome-wide studies have yielded new insights into the biological function of long noncoding RNAs (lncRNAs), predominantly through analysis of their genomic addresses. These studies have revealed that a large number of lncRNAs map to regulatory elements in eukaryotic genome regions known as promoter and enhancer elements. Here, we review the principles of current methodologies for analyzing lncRNAs with high-throughput sequencing approaches. These include (1) direct RNA sequencing, (2) sequencing coupled with transcription, and (3) isolation of protein complexes associated with lncRNAs followed by high-throughput sequencing. Within these categories, we also describe detailed protocols for chromatin associated RNA sequencing, nascent transcript Global run-on sequencing, and photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation. PMID- 27372766 TI - Identifying Centromeric RNAs Involved in Histone Dynamics In Vivo. AB - Over the last decade, the long accepted dogma that heterochromatin is silent has been challenged by increasing evidence of active transcription in these apocryphally annotated quiescent regions of the genome. The recent discovery of noncoding RNAs (ncRNAs) originating from, or localizing to, centromeres, pericentromeres, and telomeres (ie, constitutive heterochromatin) suggest a potential role for ncRNAs in genome integrity. This new paradigm suggests that ncRNAs may recruit chromatin-binding factors, stabilize the higher order folded state of the chromatin fiber, and participate in regulation of processes such as transcription-mediated nucleosome assembly. Thus, identifying, purifying, and elucidating the function of ncRNAs has the potential to provide key insights into genome organization and is currently a topic of intense experimental investigation. PMID- 27372767 TI - Preface. PMID- 27372768 TI - Preprocedural Assessment for Sedation in Gastrointestinal Endoscopy. AB - The role of the anesthesia service in sedation for gastrointestinal endoscopy (GIE) has been steadily increasing. The goals of preprocedural assessment are determined by the specific details of the procedure, the issues related to the illness that requires the endoscopy, comorbidities, the goals for sedation, and the risk of complications from the sedation and the endoscopic procedure. Rather than consider these issues as separate entities, they should be considered as part of a continuum of preparation for GIE. This is told from the perspective of an anesthesiologist who regularly participates in the full range of sedation for GIE. PMID- 27372769 TI - Training and Competency in Sedation Practice in Gastrointestinal Endoscopy. AB - The practice of endoscopic sedation requires a thorough understanding of preprocedural assessment, sedation pharmacology, intraprocedure monitoring, adverse event management, and postprocedural care. The training process has become increasingly standardized and entails knowledge and practice-based components. The use of propofol in particular requires a higher level of structured training owing to its narrow therapeutic window. Simulation has increased opportunities for practice-based training in a controlled environment. After completion of training, the endoscopist must demonstrate competence in theoretical understanding and technical ability to administer sedation. Although individual institutions have certification processes, there is a lack of validated, standardized methods to confirm competence. PMID- 27372770 TI - Endoscopic Sedation: Medicolegal Considerations. AB - Goals of endoscopic sedation are to provide patients with a successful procedure, and ensure that they remain safe and are relieved from anxiety and discomfort; agents should provide efficient, appropriate sedation and allow patients to recover rapidly. Sedation is usually safe and effective; however, complications may ensue. This paper outlines some medicolegal aspects of endoscopic sedation, including informed consent, possible withdrawal of consent during the procedure, standard of care for monitoring sedation, use of anesthesia personnel to deliver sedation, and new agents and devices. PMID- 27372771 TI - Non-Operating Room Anesthesia in the Endoscopy Unit. AB - The term, non-operating room anesthesia, describes a location remote from the main operating suites and closer to the patient, including areas that offer specialized procedures, like endoscopy suites, cardiac catheterization laboratories, bronchoscopy suites, and invasive radiology suites. There has been an exponential growth in such procedures and they present challenges in both organizational aspects and administration of anesthesia. This article explores the requirements for the location, preoperative evaluation and patient selection, monitoring, anesthesia technique, and postoperative management at these sites. There is a need to better define the role of the anesthesia personnel at these remote sites. PMID- 27372772 TI - Endoscopist-Directed Propofol. AB - Endoscopist-directed propofol (EDP) refers to delivery of propofol for endoscopic sedation under the direction of an endoscopist without any involvement of an anesthesia specialist (anesthesiologist or nurse anesthetist). EDP has been proven to be safe and is also cost-effective compared with the anesthetist delivered sedation for endoscopy. EDP has been endorsed by US gastroenterology societies as an appropriate paradigm for clinical practice. EDP has proliferated in Switzerland and Germany, but its expansion in the United States has been limited by financial disincentives, concerns about medical-legal risk for endoscopists, and regulatory obstacles. PMID- 27372773 TI - Extended Monitoring during Endoscopy. AB - Gastrointestinal endoscopic sedation has improved procedural and patient outcomes but is associated with attendant risks of oversedation and hemodynamic compromise. Therefore, close monitoring during endoscopic procedures using sedation is critical. This monitoring begins with appropriate staff trained in visual assessment of patients and analysis of basic physiologic parameters. It also mandates an array of devices widely used in practice to evaluate hemodynamics, oxygenation, ventilation, and depth of sedation. The authors review the evidence behind monitoring practices and current society recommendations and discuss forthcoming technologies and techniques that are poised to improve noninvasive monitoring of patients under endoscopic sedation. PMID- 27372774 TI - Sedation and Monitoring in the Pediatric Patient during Gastrointestinal Endoscopy. AB - Sedation is a fundamental component of pediatric gastrointestinal procedures. The 2 main types of sedation for pediatric endoscopy remain general anesthesia and procedural sedation. Although anesthesiologist-administered sedation protocols are more common, there is no ideal regimen for endoscopy in children. This article discusses specific levels of sedation for endoscopy as well as various regimens that can be used to achieve each. Risks and considerations that may be specific to performing gastrointestinal procedures in children are reviewed. Finally, potential future directions for sedation and monitoring that may change the practice of pediatric gastroenterology and ultimately patient outcomes are examined. PMID- 27372775 TI - Sedation Challenges: Obesity and Sleep Apnea. AB - This article reviews the data for diagnostic and uncomplicated therapeutic upper endoscopy, which show it is safe and effective to perform the procedure under moderate sedation with a combination of benzodiazepine and opioids. For more complex procedures or for superobese patients anesthesia support is recommended. Performing endoscopy in this population should alert providers to plan carefully and individualize sedation plans because there is no objective way to quantify this risk pre-endoscopically. PMID- 27372776 TI - Sedation in the Ambulatory Endoscopy Center: Optimizing Safety, Expectations and Throughput. AB - In the United States, sedation and analgesia are the standard of practice when endoscopic procedures are performed in the ambulatory endoscopy center. Over the last 30 years, there has been a dramatic shift of endoscopic procedures from the hospital outpatient department to ambulatory endoscopy centers. This article will discuss sedation and analgesia in the ambulatory endoscopy center as it relates to optimizing safety, patient expectations, and efficiency. PMID- 27372777 TI - Quality Assurance in the Endoscopy Suite: Sedation and Monitoring. AB - Recent development and expansion of endoscopy units has necessitated similar progress in the quality assurance of procedure sedation and monitoring. The large number of endoscopic procedures performed annually underlies the need for standardized quality initiatives focused on mitigating patient risk before, during, and immediately after endoscopic sedation, as well as improving procedure outcomes and patient satisfaction. Specific standards are needed for newer sedation modalities, including propofol administration. This article reviews the current guidelines and literature concerning quality assurance and endoscopic procedure sedation. PMID- 27372778 TI - Computer-Assisted and Patient-Controlled Sedation Platforms. AB - As the number and complexity of endoscopic procedures increase, the role of sedation has been integral in patient and physician satisfaction. This article discusses the advances of computer-assisted and patient-controlled platforms. These computer-assisted and patient-controlled platforms use different anesthetics and analgesics, all with the intent of achieving improved consistency in the level of sedation, appropriate to the needs of patients, while also improving patient safety. These systems have been around for decades; however, few are approved for use in the United States, and several still require further study before broad clinical application. PMID- 27372779 TI - On the Horizon: The Future of Procedural Sedation. AB - Sedation plays an integral part in endoscopy. By achieving patient comfort, it allows for a better examination and enhances patient satisfaction. Various medications have been used, propofol being the current favorite. With emphasis on patient safety and quality of endoscopy, various new medications in different combinations are being used to achieve adequate sedation and not escalate the cost of the procedure. With the advent of newer medications and newer modalities to administer these medications, there is need for more specialized training for the endoscopist to feel comfortable while using these medications. PMID- 27372780 TI - Sedation for Gastrointestinal Endoscopy: An Uneasy State of the Art. PMID- 27372781 TI - Sedation and Monitoring in Gastrointestinal Endoscopy. PMID- 27372782 TI - Cancer treatment-related cardiac toxicity: prevention, assessment and management. AB - Cancer therapies, especially anthracyclines and monoclonal antibodies, have been linked with increased rates of cardiotoxicity. The development of some cardiac side effects happens over several months, and changes in ejection fraction can be detected long before permanent damage or disability occurs. Advanced heart failure could be averted with better and earlier detection. Methodologies for early detection of cardiac changes include stress echocardiograms, cardiac velocity measurements, radionuclide imaging, cardiac MRI and several potential biomarkers. Many agents have been described for prophylaxis of cardiac events precipitated by cancer therapy. Prophylactic use of beta-blockers and ACE inhibitors may be considered for use with trastuzumab in breast cancer as tolerated. Recovery of cardiac function is possible early after the injury from a cancer therapy. Late complications for coronary artery disease, hypertension and arrhythmia are underappreciated. Treatments for severe cancer therapy-related cardiac complications follow the existing paradigms for congestive heart failure and coronary artery disease, although outcomes for cancer patients differ from outcomes for non-cancer patients. PMID- 27372784 TI - [Not Available]. PMID- 27372783 TI - Failure mode and effects analysis of witnessing protocols for ensuring traceability during PGD/PGS cycles. AB - Preimplantation genetic diagnosis and aneuploidy testing (PGD/PGS) use is constantly growing in IVF, and embryo/biopsy traceability during the additional laboratory procedures needed is pivotal. An electronic witnessing system (EWS), which showed a significant value in decreasing mismatch occurrence and increasing detection possibilities during standard care IVF, still does not guarantee the same level of efficiency during PGD/PGS cycles. Specifically, EWS cannot follow single embryos throughout the procedure. This is however critical when an unambiguous diagnosis corresponds to each embryo. Failure Mode and Effects Analysis (FMEA) is a proactive method generally adopted to define tools ensuring safety along a procedure. Due to the implementation of a large quantitative PCR (qPCR)-based blastocyst stage PGD/PGS programme in our centre, and to evaluate the potential procedural risks, a FMEA was performed in September 2014. Forty four failure modes were identified, among which six were given a moderate risk priority number (>15) (RPN; product of estimated occurrence, severity and detection). Specific corrective measures were then introduced and implemented, and a second evaluation performed six months later. The meticulous and careful application of such measures allowed the risks to be decreased along the whole protocol, by reducing their estimated occurrence and/or increasing detection possibilities. PMID- 27372785 TI - [Not Available]. PMID- 27372786 TI - [Not Available]. PMID- 27372787 TI - [Not Available]. PMID- 27372788 TI - [Not Available]. PMID- 27372789 TI - [Not Available]. PMID- 27372790 TI - [Not Available]. PMID- 27372792 TI - [Not Available]. PMID- 27372791 TI - [Not Available]. PMID- 27372793 TI - [Not Available]. PMID- 27372795 TI - [Not Available]. PMID- 27372794 TI - [Not Available]. PMID- 27372796 TI - [Not Available]. PMID- 27372798 TI - [Not Available]. PMID- 27372797 TI - [Not Available]. PMID- 27372799 TI - [Not Available]. PMID- 27372800 TI - [Not Available]. PMID- 27372801 TI - Examining the independent protective effect of subjective well-being on severe psychological distress among Canadian adults with a history of child maltreatment. AB - The purpose of this study was to examine the independent protective effect of subjective well-being on severe psychological distress among adult Canadians with a history of child maltreatment. Data for this study were obtained from the 2012 Canadian Community Health Survey-Mental Health (CCHS-MH). A sample of 8126 respondents aged 20-69 years old who experienced at least one child maltreatment event was analyzed using binary logistic regression with severe psychological distress as the outcome variable. Of the 8126 respondents with a history of child maltreatment, 3.9% experienced severe psychological distress within the past month. Results from the multivariate logistic regression revealed that emotional and psychological well-being each had a significant effect on severe psychological distress. For each unit increase in emotional well-being, the odds of a respondent having severe psychological distress were predicted to decrease by a factor of 28% and for each unit increase in psychological well-being, the odds of a respondent having severe psychological distress were predicted to decrease by a factor of 10%, net the effect of demographic, socioeconomic, and health factors. Other factors associated with psychological distress included: younger age, poor self-perceived physical health, and chronic condition. Having post-secondary education, having a higher income, and being non-White predicted lower odds of severe psychological distress. Although, child maltreatment is associated with stressful life events later in adulthood, subjective well-being could serve as a protective factor against severe psychological distress among adults who experienced maltreatment when they were children. PMID- 27372802 TI - Molecular mechanism of lipid-induced cardiac insulin resistance and contractile dysfunction. AB - Long-chain fatty acids are the main cardiac substrates from which ATP is generated continually to serve the high energy demand and sustain the normal function of the heart. Under healthy conditions, fatty acid beta-oxidation produces 50-70% of the energy demands with the remainder largely accounted for by glucose. Chronically increased dietary lipid supply often leads to excess lipid accumulation in the heart, which is linked to a variety of maladaptive phenomena, such as insulin resistance, cardiac hypertrophy and contractile dysfunction. CD36, the predominant cardiac fatty acid transporter, has a key role in setting the heart on a road to contractile dysfunction upon the onset of chronic lipid oversupply by translocating to the cell surface and opening the cellular 'doors' for fatty acids. The sequence of events after the CD36-mediated myocellular lipid accumulation is less understood, but in general it has been accepted that the excessively imported lipids cause insulin resistance, which in turn leads to contractile dysfunction. There are several gaps of knowledge in this proposed order of events which this review aims to discuss. First, the molecular mechanisms underlying lipid-induced insulin resistance are not yet completely disclosed. Specifically, several mediators have been proposed, such as diacylglycerols, ceramides, peroxisome proliferator-activated receptors (PPAR), inflammatory kinases and reactive oxygen species (ROS), but their relative contributions to the onset of insulin resistance and their putatively synergistic actions are topics of controversy. Second, there are also pieces of evidence that lipids can induce contractile dysfunction independently of insulin resistance. Perhaps, a more integrative view is needed, in which several lipid-induced pathways operate synergistically or in parallel to induce contractile dysfunction. Unraveling of these processes is expected to be important in designing effective therapeutic strategies to protect the lipid-overloaded heart. PMID- 27372803 TI - Assessing the Impact of Food Assistance on Stigma Among People Living with HIV in Uganda Using the HIV/AIDS Stigma Instrument-PLWA (HASI-P). AB - HIV-related stigma among persons living with HIV/AIDS (PLHIV) is prevalent throughout sub-Saharan Africa. There is limited evidence, however, on which interventions are effective in reducing it. We used data from a prospective impact evaluation of a 12-month food assistance intervention among 904 antiretroviral therapy (ART)- naive PLHIV in Uganda to examine the program impact on stigma. Stigma was measured using the comprehensive HASI-P scale, which demonstrated good internal consistency (Cronbach's alpha = 0.87) and was correlated with several related constructs including physical and mental health related quality of life, disclosure, and physical health symptoms in the sample. Using quasi-experimental difference-in-difference matching methods to better infer causality, we tested whether the intervention improved the overall stigma scale and its subscales. The food assistance intervention had a significant effect on reported internalized (but not external) stigma of approximately 0.2 SD (p < 0.01). The HASI-P stigma scale is a useful tool for measuring and tracking stigma. Food assistance interventions, embedded in an HIV care program, can reduce internalized stigma. PMID- 27372804 TI - Injection of tennis elbow: Hit and miss? A cadaveric study of injection accuracy. AB - PURPOSE: Different injection therapies are used in the treatment of lateral epicondylitis (LE). Usually, the extensor carpi radialis brevis (ECRB) tendon is affected. Therefore, an injection should be aimed at the origin of this tendon. This study demonstrates the accuracy of manual injections in the treatment of LE. METHODS: Ten surgeons have injected a cadaver elbow with acrylic paint, using the same injection technique (i.e. number of perforations, amount of injected fluid) that they in daily practice would use in the treatment of LE. After the injection, an arthroscopy and dissection of the elbow were performed. The injection technique and localization of acrylic paint were reported. RESULTS: Only a third of the injections were (partially) localized in the ECRB tendon; 60 % were localized intra-articular. CONCLUSION: Injections carried out manually for the treatment of LE are not accurate, resulting in the majority being localized intra-articular. For future research to the effect of injection therapy in the treatment of LE, it is important that injections should be performed in a reproducible and standardized way. PMID- 27372805 TI - Hypolipidemic and Antioxidant Properties of Hot Pepper Flower (Capsicum annuum L.). AB - At present, the various medical treatments of obesity involve side effects. The aim of the research is therefore to find natural compounds that have anti-obesity activity with minimum disadvantages. In this study, the hypolipidemic effect of hydroalcoholic extract of flowers from Capsicum annuum L. was examined through the evaluation of inhibition of pancreatic lipase. Antioxidant activity was assessed using different tests: 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) and lipid peroxidation inhibition assays. Phytochemical analysis indicated that total phenolic and flavonoid content in the extract was 128.7 +/- 4.5 mg chlorogenic acid equivalent/g of crude extract and 17.66 +/- 0.11 mg of quercetin equivalent/g of crude extract, respectively. The extract inhibited pancreatic lipase with IC50 value equal to 3.54 +/- 0.18 mg/ml. It also inhibited lipid peroxidation with IC50 value of 27.61 +/- 2.25 MUg/ml after 30 min of incubation and 41.69 +/- 1.13 MUg/ml after 60 min of incubation. The IC50 value of radical scavenging activity was 51.90 +/- 2.03 MUg/ml. The extract was also able to inhibit NO production (IC50 = of 264.3 +/- 7.98 MUg/ml) without showing any cytotoxic effect. PMID- 27372806 TI - Production of (28)Mg by bombardment of (nat)Cl with 200MeV protons: Proof-of concept study for a stacked LiCl target. AB - A stacked target consisting of ten Al-encapsulated LiCl discs, for producing (28)Mg via the (nat)Cl(p,X)(28)Mg process in the energy region 50-200MeV, is described. This target was irradiated with a 200MeV beam at an intensity of 100nA, providing information on both yield and outscattering losses. Results of a Monte Carlo modelling of the beam and target, by means of the code MCNPX, are also presented. Similar Al-encapsulated LiCl discs were individually irradiated with 66MeV proton beams of 65 and 90MUA, respectively, to study their behaviour under high-intensity bombardment. Once removed from the Al encapsulation, the (28)Mg can be separated from the LiCl target material efficiently, using a 12.5cm x 1cm(2) column containing Purolite S950 chelating resin. The eluate contains (7)Be but no other measurable radio-contaminants. The removal of the (7)Be contaminant is performed by cation exchange chromatography in malate media, with (28)Mg being retained by the resin and (7)Be eluted. PMID- 27372807 TI - Automated synthesis of 4-[(18)F]fluoroanisole, [(18)F]DAA1106 and 4-[(18)F]FPhe using Cu-mediated radiofluorination under "minimalist" conditions. AB - The application of the "minimalist" approach to Cu-mediated radiofluorination allows the efficient preparation of (18)F-labeled arenes regardless of their electronic properties. The implementation of this methodology on a commercially available synthesis module (hotbox(three), Scintomics, Germany) enabled the automated production of 4-[(18)F]fluoroanisole as well as the clinically relevant PET-tracers, 4-[(18)F]FPhe and [(18)F]DAA1106, in radiochemical yields of 41-61% and radiochemical purities of >95% within 30-60min. These results demonstrated the high efficacy and versatility of the developed method that will open up opportunities for a broad application of Cu-mediated radiofluorination in PET chemistry. PMID- 27372808 TI - In vivo spatial correlation between (18)F-BPA and (18)F-FDG uptakes in head and neck cancer. AB - BACKGROUND AND PURPOSE: Borono-2-(18)F-fluoro-phenylalanine ((18)F-BPA) has been used to estimate the therapeutic effects of boron neutron capture therapy (BNCT), while (18)F-fluorodeoxyglucose ((18)F-FDG) is the most commonly used positron emission tomography (PET) radiopharmaceutical in a routine clinical use. The aim of the present study was to evaluate spatial correlation between (18)F-BPA and (18)F-FDG uptakes using a deformable image registration-based technique. MATERIAL AND METHODS: Ten patients with head and neck cancer were recruited from January 2014 to December 2014. All patients underwent whole-body (18)F-BPA PET/computed tomography (CT) and (18)F-FDG PET/CT within a 2-week period. For each patient, (18)F-BPA PET/CT and (18)F-FDG PET/CT images were aligned based on a deformable image registration framework. The voxel-by-voxel spatial correlation of standardized uptake value (SUV) within the tumor was analyzed. RESULTS: Our image processing framework achieved accurate and validated registration results for each PET/CT image. In 9/10 patients, the spatial distribution of SUVs between (18)F-BPA and (18)F-FDG showed a significant, positive correlation in the tumor volume. CONCLUSIONS: Deformable image registration-based voxel-wise analysis demonstrated a spatial correlation between (18)F-BPA and (18)F-FDG uptakes in the head and neck cancer. A tumor sub-volume with a high (18)F-FDG uptake may predict high accumulation of (18)F-BPA. PMID- 27372809 TI - Development of novel 1,4-benzodiazepine-based Michael acceptors as antitrypanosomal agents. AB - Novel 1,4-benzodiazepines, endowed with a Michael acceptor moiety, were designed taking advantage of a computational prediction of their pharmacokinetic parameters. Among all the synthesized derivatives, we identified a new lead compound (i.e., 4a), bearing a vinyl ketone warhead and endowed with a promising antitrypanosomal activity against Trypanosoma brucei brucei (IC50=5.29MUM), coupled with a lack of cytotoxicity towards mammalian cells (TC50 >100MUM). PMID- 27372811 TI - [Not Available]. PMID- 27372810 TI - Stress-related biobehavioral responses, symptoms, and physical activity among female veterans in the community: An exploratory study. AB - BACKGROUND: Female veterans experience multiple stresses during their lifetime. Some of them seek care in the civilian community. Common physical and psychological symptoms among female veterans include pain, fatigue, sleep quality, and depression. Physical activity has the potential to improve their well-being. OBJECTIVES: This study was guided by the concept of allostasis. The purpose of the study was to determine the associations among stress-related biobehavioral responses and symptoms as well as to determine if physical activity moderated these associations among female veterans. DESIGN/SETTINGS/PARTICIPANTS/METHODS: A cross-sectional and exploratory design was implemented among 82 female veterans (46+/-10.57years old) at a community event. Self-reported questionnaires and blood and hair samples were collected. Descriptive statistics and multivariate analyses were applied in this secondary data analysis. FINDINGS: Female veterans experienced moderate perceived stress and greater body mass index, C-reactive protein, and hair cortisol levels at the same time as they reported moderate levels of pain and fatigue, poor sleep quality, and considerable depressive symptoms. The findings showed that greater body mass index was significantly associated with more severe pain and poor sleep quality. Physical activity negatively moderated the relationship between perceived stress and pain. CONCLUSION: Female veterans need services to manage body weight and help them engage in physical activity. Nurse educators are responsible for instructing nurses to properly identify female veterans in the civilian community facility and to provide care in a respectful manner. PMID- 27372812 TI - [Not Available]. PMID- 27372813 TI - [Not Available]. PMID- 27372814 TI - [Not Available]. PMID- 27372815 TI - [Not Available]. PMID- 27372817 TI - [Not Available]. PMID- 27372816 TI - [Not Available]. PMID- 27372818 TI - [Not Available]. PMID- 27372820 TI - [Not Available]. PMID- 27372819 TI - [Not Available]. PMID- 27372821 TI - [Not Available]. PMID- 27372822 TI - [Not Available]. PMID- 27372823 TI - [Not Available]. PMID- 27372825 TI - [Not Available]. PMID- 27372824 TI - [Not Available]. PMID- 27372826 TI - [Not Available]. PMID- 27372827 TI - [Not Available]. PMID- 27372829 TI - [Not Available]. PMID- 27372828 TI - [Not Available]. PMID- 27372830 TI - Special Issue on the "Interrelations between non-linguistic and linguistic representations of cognition and action in development". PMID- 27372831 TI - The Benefits and Costs of a Rose-Colored Hindsight. AB - Self-serving biases lead people to see themselves and their future through rose colored glasses. New research by Kouchaki and Gino suggests this rosy view also extends backwards: memories of unethical behavior are less vivid than memories of good deeds. This so-called 'unethical amnesia' has many individual benefits, but also carries social costs. PMID- 27372832 TI - Prevalence of Adolescent Problem Gambling: A Systematic Review of Recent Research. AB - Previous research has shown that gambling is a popular activity among adolescents. Following a rapid expansion of legalized gambling opportunities and the emergence of new forms of gambling, many researchers have carried out studies on adolescent gambling and problem gambling. The present paper reviews studies that have been conducted worldwide since 2000, and then presents a more detailed picture of adolescent gambling research in Europe, by providing a country-by country analysis. After an extensive search on academic databases and following an exclusion process, 44 studies were identified. The findings showed that 0.2 12.3 % of youth meet criteria for problem gambling, notwithstanding differences among assessment instruments, cut-offs, and timeframes. However, despite this variability, several demographic characteristics were associated with adolescent gambling involvement and problem gambling. It is concluded that a small but significant minority of adolescents have gambling-related problems. Such findings will hopefully encourage more research into youth gambling to further understand the determinants of this phenomenon. PMID- 27372833 TI - Successful implementation of Lynch syndrome screening in a safety net institution. AB - Lynch syndrome (LS) is the most common cause of hereditary colorectal cancer (CRC), and national guidelines recommend screening patients with CRC for LS. However, there is a paucity of data related to Lynch syndrome in the underserved population, in which unique issues of access, cultural beliefs regarding cancer, language barriers, immigration status, and financial restraints exist. We performed a descriptive, retrospective review of a selective LS screening protocol at an urban safety net hospital between 2009 and 2014 with the aim of describing the detected prevalence of LS as well as reporting the high quality and suboptimal screening rates. A total of 154 cases of CRC were identified over the 5-year period, of which 57 met selective LS screening criteria. Eleven patients had a positive screen, and three patients were diagnosed with LS, leading to an overall detected LS prevalence of 1.9 %. The rate of high quality screen was greater than 90 %, consistent with prior studies. Thus, we show that screening for LS in a safety net hospital can be successful in achieving high quality screening and provide an example for other public hospitals considering implementation of hereditary cancer screening. PMID- 27372834 TI - Counsellee's experience of cancer genetic counselling with pedigrees that automatically incorporate genealogical and cancer database information. AB - While pedigree drawing software is often utilised in genetic services, the use of genealogical databases in genetic counselling is unusual. This is mainly because of the unavailability of such databases in most countries. Electronically generated pedigrees used for cancer genetic counselling in Iceland create pedigrees that automatically incorporate information from a large, comprehensive genealogy database and nation-wide cancer registry. The aim of this descriptive qualitative study was to explore counsellees' experiences of genetic services, including family history taking, using these electronically generated pedigrees. Four online focus groups with 19 participants were formed, using an asynchronous posting method. Participants were encouraged to discuss their responses to questions posted on the website by the researcher. The main themes arising were motivation, information and trust, impact of testing and emotional responses. Most of the participants expressed trust in the method of using electronically generated pedigrees, although some voiced worries about information safety. Many experienced worry and anxiety while waiting for results of genetic testing, but limited survival guilt was noted. Family communication was either unchanged or improved following genetic counselling. The use of electronically generated pedigrees was well received by participants, and they trusted the information obtained via the databases. Age did not seem to influence responses. These results may be indicative of the particular culture in Iceland, where genealogical information is well known and freely shared. Further studies are needed to determine whether use of similar approaches to genealogical information gathering may be acceptable elsewhere. PMID- 27372835 TI - Consonantal overlap effects in a perceptual matching task. AB - This study investigates the processing of letter position coding by exploring whether or not two explicitly presented words that share the same consonants, but that differ in their vowels, exert mutual interference more than two words that do not share their consonants. In an explicit perceptual matching task, word targets were preceded by a word reference that could share all the consonants either at the same position or in a different absolute position (while keeping their relative position intact) or preceded by an unrelated reference. Experiment 1 showed larger discrimination costs for pairs sharing the consonants at the same position than for pairs sharing their consonants in a different position. Experiment 2 investigated when and how the types of overlap influence word target processing by using event-related potential recordings. The ERP results showed a Relatedness effect only for targets that share the consonants at the same position from 120 to 600 ms post-target onset, whereas targets that share their consonants in different positions in the string produced null effects. Altogether, these data suggest that targets containing the same consonants included in the references in the same positions are processed as being highly similar to them, thus distorting target processing. Furthermore, these data suggest possible mechanisms of competition between lexical representations of the reference and target stimuli. PMID- 27372836 TI - A pilot study exploring the relationship between lifelong learning and factors associated with evidence-based medicine. AB - OBJECTIVES: To explore possible relationships between residents' lifelong learning orientation, skills in practicing evidence-based medicine (EBM), and perceptions of the environment for learning and practicing EBM. METHODS: This was a pilot study with a cross-sectional survey design. Out of 60 residents in a medical residency program, 29 participated in the study. Data were collected using a survey that comprised three sections: the JeffSPLL Scale, EBM Environment Scale, and an EBM skill questionnaire. Data were analyzed using SPSS and were reported with descriptive and inferential statistics (mean, standard deviation, Pearson's correlation, and a two-sample t-test). RESULTS: Mean scores on the JeffSPLL Scale were significantly correlated with perceptions of the EBM Scale and use of EBM resources to keep up to date or solve a specific patient care problem. There was a significant correlation between mean scores on the EBM Scale and hours per week spent in reading medical literature to solve a patient care problem. Two-sample t-tests show that residents with previous training in research methods had significantly higher scores on the JeffSPLL Scale (p=0.04), EBM Scale (p=0.006), and self-efficacy scale (p =0.024). CONCLUSIONS: Given the fact that physicians are expected to be lifelong learners over the course of their professional career, developing residents' EBM skills and creating interventions to improve specific areas in the EBM environment would likely foster residents' lifelong learning orientation. PMID- 27372837 TI - Sex-Specific Effects of Prenatal Stress on Memory and Markers of Neuronal Activity in Juvenile Rats. AB - Stress during pregnancy can increase the incidence of emotional problems, learning and language difficulties in human infants and pre-adolescents. Most preclinical studies in rats that attempted to find experimental support for these observations were performed in adult male offspring, but the results are inconsistent. The aim of the current study was to examine the effect of prenatal stress on novel object recognition (NOR) and spatial learning and memory in the Morris water maze (MWM) of juvenile rats of both sexes. By the use of fluorescence immunohistochemistry and protein measurements by Western blot, we measured the expression of markers of neurogenesis (doublecortin, DCX) and neuronal activity that are important for synaptic plasticity and learning (c-fos, GluR1, nNOS). Since neuronal activity in the developing and adult brain can be regulated by astrocytes, we also measured the number of astrocytes and the expression of two astroglial proteins (GFAP and S100B) in the stress-responsive hippocampal dentate gyrus (DG). Experiments were performed on littermates of rats in which its effects on behavior were measured. We found for the first time that juvenile females performed better than males in the NOR and MWM tests. They also had higher densities of DCX and c-fos in the DG, together with the expression of nNOS and GluR1 in the subgranular zone (SGZ) of the DG. There were no sex differences in the expression of GFAP and S100B in astrocytes. Prenatal stress did not affect NOR in females, but improved it in males, together with an increase in DCX+ and c-fos, the number of GFAP-expressing astrocytes and the intensity of GFAP and S100B immunofluorescence in the DG. Staining intensity of GluR1 and nNOS in the hilus and SGZ of the DG, and protein expression in the whole DG, was unchanged in prenatally stressed males. Thus, prenatal stress changed the behavior and expression of key proteins in the DG to resemble that in females. A reduction in plasma testosterone, which although not attaining statistical significance was associated with that in anogenital distance, may contribute to the effect of prenatal stress in males. In females, prenatal stress had no effect on c-fos, DCX or the number of astrocytes but reduced the staining intensity of GluR1 and nNOS. Protein expression of nNOS was also significantly lower than that in prenatally stressed males. The differential effects of prenatal stress on hippocampal neuronal and glial markers may help to explain the sex-dependent effect on spatial learning in prepubertal rats. PMID- 27372838 TI - Effects of 8-halo-7-deaza-2'-deoxyguanosine triphosphate on DNA synthesis by DNA polymerases and cell proliferation. AB - 8-OxodG (8-oxo-2'-deoxyguanosine) is representative of nucleoside damage and shows a genotoxicity. To significantly reveal the contributions of 7-NH and C8 oxygen to the mutagenic effect of 8-oxodG by DNA polymerases, we evaluated the effects of the 8-halo-7-deaza-dG (8-halogenated 7-deaza-2'-deoxyguanosine) derivatives by DNA polymerases. 8-Halo-7-deaza-dGTPs were poorly incorporated by both KF(exo(-)) and human DNA polymerase beta opposite dC or dA into the template DNA. Furthermore, it was found that KF(exo(-)) was very sensitive to the introduction of the C8-halogen, while polymerase beta can accommodate the C8 halogen resulting in an efficient dCTP insertion opposite the 8-halo-7-deaza-dG in the template DNA. These results indicate that strong hydrogen bonding between 7-NH in the 8-oxo-G nucleobase and 1-N in the adenine at the active site of the DNA polymerase is required for the mutagenic effects. Whereas, I-deaza-dGTP shows an antiproliferative effect for the HeLa cells, suggesting that it could become a candidate as a new antitumor agent. PMID- 27372839 TI - Synthesis, photophysical properties of triazolyl-donor/acceptor chromophores decorated unnatural amino acids: Incorporation of a pair into Leu-enkephalin peptide and application of triazolylperylene amino acid in sensing BSA. AB - The research in the field of design and synthesis of unnatural amino acids is growing at a fast space for the increasing demand of proteins of potential therapeutics and many other diversified novel functional applications. Thus, we report herein the design and synthesis of microenvironment sensitive fluorescent triazolyl unnatural amino acids (UNAA) decorated with donor and/or acceptor aromatic chromophores via click chemistry. The synthesized fluorescent amino acids show interesting solvatochromic characteristic and/or intramolecular charge transfer (ICT) feature as is revealed from the UV-visible, fluorescence photophysical properties and DFT/TDDFT calculation. HOMO-LUMO distribution shows that the emissive states of some of the amino acids are characterized with more significant electron redistribution between the triazolyl moiety and the aromatic chromophores linked to it leading to modulated emission property. A pair of donor acceptor amino acid shows interesting photophysical interaction property indicating a FRET quenching event. Furthermore, one of the amino acid, triazolyl perylene amino acid, has been exploited for studying interaction with BSA and found that it is able to sense BSA with an enhancement of fluorescence intensity. Finally, we incorporated a pair of donor/acceptor amino acids into a Leu enkephalin analogue pentapeptide which was found to adopt predominantly type II beta-turn conformation. We envisage that our investigation is of importance for the development of new fluorescent donor-acceptor unnatural amino acids a pair of which can be exploited for generating fluorescent peptidomimetic probe of interesting photophysical property for applications in studying peptide-protein interaction. PMID- 27372840 TI - Novel FXR (farnesoid X receptor) modulators: Potential therapies for cholesterol gallstone disease. AB - Metabolic disorders such as diabetes are known risk factors for developing cholesterol gallstone disease (CGD). Cholesterol gallstone disease is one of the most prevalent digestive diseases, leading to considerable financial and social burden worldwide. Ursodeoxycholic acid (UDCA) is the only bile acid drug approved by FDA for the non-surgical treatment of gallstones. However, the molecular link between UDCA and CGD is unclear. Previous data suggest that the farnesoid X receptor (FXR), a bile acid nuclear receptor, may protect against the development of CGD. In studies aimed at identifying the role of FXR, we recently identify a novel chemical tool, 6EUDCA (6-alphaethyl-ursodeoxycholic acid), a synthetic derivative of UDCA, for studying FXR. We found that 6EUDCA binds FXR stronger than UDCA in a TR-FRET binding assay. This result was supported by computational docking models that suggest 6EUDCA forms a more extensive hydrogen bound network with FXR. Interestingly, neither compound could activate FXR target genes in human nor mouse liver cells, suggesting UDCA and 6EUDCA activate non-genomic signals in an FXR-dependent manner. Overall these studies may lead to the identification of a novel mechanism by which bile acids regulate cell function, and 6EUDCA may be an effective targeted CGD therapeutic. PMID- 27372841 TI - Hybrid palliation and pulmonary artery architecture. PMID- 27372842 TI - Hemodynamic and ventilatory responses during exercise in chronic thromboembolic disease. AB - BACKGROUND: Patients with chronic thromboembolic disease (CTED) may suffer from exercise intolerance without pulmonary hypertension at rest. Pulmonary endarterectomy (PEA) for symptomatic CTED results in improvement of symptoms and quality of life. Neither the pathophysiology of the exercise limitation nor the underlying mechanisms of the PEA-induced improvement have been studied previously. OBJECTIVES: We studied hemodynamic and ventilatory responses upon exercise in 14 patients with CTED. After 1 year, we studied the underlying physiologic mechanisms of the PEA-induced symptomatic improvement. METHODS: Cardiopulmonary exercise testing (CPET) was performed during right heart catheterization, and noninvasive CPET was performed 1 year postoperatively. RESULTS: During exercise, we observed abnormal pulmonary vascular responses, that is, a steep mean pulmonary artery pressure/cardiac output (2.7 +/- 1.2 mm Hg.min.L(-1)), and low pulmonary vascular compliance (2.8 +/- 1.1 mL.mm Hg(-1)); mean pulmonary artery pressure/cardiac output slope correlated with dead-space ventilation (r = 0.586; P = .028) and ventilatory equivalents for carbon dioxide slope (r = .580; P = .030). Postoperatively, the improvement observed in exercise capacity was related to improvements in CPET-derived parameters pointing to restoration of right ventricle stroke volume response (oxygen pulse: 11.7 +/- 3.1 to 13.3 +/- 3.3; P = .027; heart rate response: 80.9 +/- 12.4 to 72.0 +/- 5.7; P = .003); and, indicating improved ventilatory efficiency, the ventilatory equivalents for carbon dioxide slope decreased from 38.2 +/- 3.6 to 32.8 +/- 7.0 (P = .014). CONCLUSIONS: Patients with CTED showed an abnormal pulmonary vascular response to exercise and a decreased ventilatory efficiency. Responses after PEA point to restoration of right ventricle stroke volume response and ventilatory efficiency. PMID- 27372843 TI - Center of Pressure Speed Changes with tDCS Versus GVS in Patients with Lateropulsion after Stroke. PMID- 27372844 TI - Tolerability of Repeated Application of Transcranial Electrical Stimulation with Limited Outputs to Healthy Subjects. AB - BACKGROUND: The safety and tolerability of limited output transcranial electrical stimulation (tES) in clinical populations support a non-significant risk designation. The tolerability of long-term use in a healthy population had remained untested. OBJECTIVE: We tested the tolerability and compliance of two tES waveforms, transcranial direct current stimulation (tDCS) and modulated high frequency transcranial pulsed current stimulation (MHF-tPCS) compared to sham tDCS, applied to healthy subjects for three to five days (17-20 minutes per day) per week for up to six weeks in a communal setting. MHF-tPCS consisted of asymmetric high-frequency pulses (7-11 kHz) having a peak amplitude of 10-20 mA peak, adjusted by subject, resulting in an average current of 5-7 mA. METHOD: A total of 100 treatment blind healthy subjects were randomly assigned to one of three treatment groups: tDCS (n = 33), MHF-tPCS (n = 30), or sham-tDCS (n = 37). In order to test the role of waveform, electrode type and montage were fixed across tES and sham-tDCS arms: high-capacity self-adhering electrodes on the right lateral forehead and back of the neck. We conducted 1905 sessions (636 sham tDCS, 623 tDCS, and 646 MHF-tPCS sessions) on study volunteers over a period of six weeks. RESULTS: Common adverse events were primarily restricted to influences upon the skin and included skin tingling, itching, and mild burning sensations. The incidence of these events in the active tES treatment arms (MHF-tPCS, tDCS) was equivalent or significantly lower than their incidence in the sham-tDCS treatment arm. Other adverse events had a rarity (<5% incidence) that could not be significantly distinguished across the treatment groups. Some subjects were withdrawn from the study due to atypical headache (sham-tDCS n = 2, tDCS n = 2, and MHF-tPCS n = 3), atypical discomfort (sham-tDCS n = 0, tDCS n = 1, and MHF tPCS n = 1), or atypical skin irritation (sham-tDCS n = 2, tDCS n = 8, and MHF tPCS n = 1). The rate of compliance, elected sessions completed, for the MHF-tPCS group was significantly greater than the sham-tDCS group's compliance (p = 0.007). There were no serious adverse events in any treatment condition. CONCLUSION: We conclude that repeated application of limited output tES across extended periods, limited to the hardware, electrodes, and protocols tested here, is well tolerated in healthy subjects, as previously observed in clinical populations. PMID- 27372846 TI - Is osseointegration inflammation-triggered? AB - Bioinert endosteal implants cause a foreign body reaction, whereas bioactive ones cause osseointegration. However, the mechanisms responsible for the two modi of host response remain unclear. COX-2(-/-) animal models showed the dependence of osseointegration on prostaglandins. PGE2, a product of COX-2, augments Wnt signalling, a pathway that promotes the regeneration in many types of tissues. Recently, we demonstrated the ability of bioactive implants to recruit neutrophils and to trigger neutrophil extracellular traps (NETs), which are a potent source of PGE2. In bioinert implants no PGE2 release has been ascertained. Collectively, these findings suggest that osseointegration might be the host response to bioactive implants, novel and quite different to the so-called foreign body reaction. PMID- 27372847 TI - Hydroxychloroquine, a promising choice for coronary artery disease? AB - Coronary artery disease is a common disease that seriously threaten the health of more than 150 million people per year. Atherosclerosis is considered to be the main cause of coronary artery disease which begins with damage or injury to the inner layer of a coronary artery, sometimes as early as childhood. The damage may be caused by various factors, including: smoking, high blood pressure, hypercholesterolemia, sedentary lifestyle, diabetes and insulin resistance. Once a coronary artery disease has developed, all patients need to be treated with long term standard treatment, including heart-healthy lifestyle changes, medicines, and medical procedures or surgery. Hydroxychloroquine, an original antimalarial drug, prevents inflammation caused by lupus erythematosus and rheumatoid arthritis. It is relatively safe and well-tolerated during the treatment. Since atherosclerosis and rheumatoid arthritis have resemble mechanism and increasing clinical researches confirm that hydroxychloroquine has an important role in both anti-rheumatoid arthritis and cardiovascular protection (such as anti-platelet, anti-thrombotic, lipid-regulating, anti-hypertension, hypoglycemia, and so on), we hypothesize that hydroxychloroquine might be a promising choice to coronary artery disease patients for its multiple benefits. PMID- 27372848 TI - Use of Escherichia coli Nissle 1917 producing recombinant colicins for treatment of IBD patients. AB - Patients with Crohn's Disease and Ulcerative Colitis infected with Adherent Invasive Escherichia coli strains constitute the largest group among Inflammatory Bowel Disease subjects, when taking into account all known etiological agents of the disease. A possible link between these pathogenic bacteria and inflammation process has gained the confidence in recently published papers. Observed enteric neuroglial cells apoptosis and epithelial gaps of ileum are probably the key manifestations of inflammation, which has been shown in IBD patients in contrary to the samples taken from healthy individuals. The cascade of consecutive events from bacterial infection via inflammation to excessive apoptosis in IBD patients leads up to the aim of our hypothesis about designing of new therapeutic strategy directed to Adherent-Invasive E. coli strains. The main advantage of biological method, which will rely on application of E. coli Nissle 1917 strain as a carrier for specific recombinant colicins against AIEC strains, could probably cause a long-lasting remission of inflammation in CD and UC patients. PMID- 27372845 TI - Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. AB - This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3-13 A/m(2)) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (<=40 min, <=4 milliamperes, <=7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations. PMID- 27372849 TI - Can a transient exertion-related carotid (TERC) murmur heard during a symptom limited exercise test be used as a means for managing sports concussion? AB - We hypothesize that a transient exertion-related carotid (TERC) murmur flow murmur similar in nature to a "bruit" heard best at the carotid artery during exercise in healthy individuals can be used as a means for assessing post concussion injury exertion tolerance. Typically there are no arterial sounds heard at the carotid artery in healthy individuals. Bruit, heard at rest, is an indicator of cardiovascular disease. Listening for a flow murmur or bruit-like sounds during exercise may indicate brain blood flow autoregulation and that this audible change in brain blood flow autoregulation could be used to assess exercise tolerance. We present very preliminary evidence supporting our hypothesis in that a transient exertion-related carotid (TERC) murmur is heard at a HR (HR) of approximately 150 beats per minute (bpm) in healthy individuals and 120bpm in concussion patients. Future prospective clinical studies to validate this hypothesis and these methods may aid clinicians who manage concussion patients by using this method to help guide exertion protocols. PMID- 27372850 TI - Could angiotensin-(1-7) be connected with improvement of microvascular function in diabetic patients? Angiotensin-(1-7) iontophoresis may provide the answer. AB - Diabetes mellitus, a metabolic disorder with significant global health care burden, causes chronic microvascular and macrovascular complications that still comprise a therapeutic challenge. Angiotensin-(1-7), a heptapeptide with vasodilatory properties, has been found to restore vascular reactivity and endothelial cell function, mostly in experiments on larger isolated animal vessels and in cell cultures. The presented hypothesis suggests that angiotensin (1-7) might have beneficial effects on microvascular function that is damaged in diabetic patients, alleviating endothelial dysfunction and increasing microvascular reactivity to various vasoactive agents in diabetes. It is further proposed that iontophoresis with angiotensin-(1-7) might be used to explore this potential beneficial effect, as well as provide a possible future therapeutic delivery method for angiotensin-(1-7). Since other peptides and proteins have been previously tested and used in iontophoretic transdermal delivery, it is plausible that angiotensin-(1-7) would be a suitable candidate for transdermal iontophoretic application for research (and potentially therapeutic) purposes. If confirmed, the delineated hypothesis would have immense implications for more effective care of diabetic patients, as well as for better understanding of microcirculatory pathophysiological mechanisms in diabetes. PMID- 27372851 TI - Chronic l-menthol-induced browning of white adipose tissue hypothesis: A putative therapeutic regime for combating obesity and improving metabolic health. AB - INTRODUCTION: Obesity constitutes a serious global health concern reaching pandemic prevalence rates. The existence of functional brown adipose tissue (BAT) in adult humans has provoked intense research interest in the role of this metabolically active tissue in whole-body energy balance and body weight regulation. A number of environmental, physiological, pathological, and pharmacological stimuli have been proposed to induce BAT-mediated thermogenesis and functional thermogenic BAT-like activity in white adipose tissue (WAT), opening new avenues for therapeutic strategies based on enhancing the number of beige adipocytes in WAT. HYPOTHESIS: Recent evidence support a role of l-menthol cooling, mediated by TRPM8 receptor, on UCP1-dependent thermogenesis and BAT-like activity in classical WAT depots along with the recruitment of BAT at specific anatomical sites. l-Menthol-induced BAT thermogenesis has been suggested to occur by a beta-adrenergic-independent mechanism, avoiding potential side-effects due to extensive beta-adrenergic stimulation mediated by available beta receptor agonists. l-Menthol has been also linked to the activation of the cold-gated ion channel TRPA1. However, its role in l-menthol-induced UCP1-dependent thermogenic activity in BAT and WAT remains undetermined. White adipose tissue plasticity has important clinical implications for obesity prevention and/or treatment because higher levels of UCP1-dependent thermogenesis can lead to enhanced energy expenditure at a considerable extent. We hypothesize that chronic dietary l menthol treatment could induce TRPM8- and TRPA1-dependent WAT adaptations, resembling BAT-like activity, and overall improve whole-body metabolic health in obese and overweight individuals. CONCLUSIONS: The putative impact of chronic l menthol dietary treatment on the stimulation of BAT-like activity in classical WAT depots in humans remains unknown. A detailed experimental design has been proposed to investigate the hypothesized l-menthol-induced browning of WAT. If our hypothesis was to be confirmed, TRPM8/TRPA1-induced metabolic adaptations of WAT to BAT-like activity could provide a promising novel therapeutic approach for increasing energy expenditure, regulating body weight, and preventing obesity and its related co-morbidities in humans. PMID- 27372852 TI - Molecules in seminal plasma related to platelets in preeclampsia. AB - OBJECTIVE: Prostaglandins present in seminal fluid are actively involved in vascular and non-vascular smooth muscle maintenance, reproduction, and inflammatory processes. Seminal plasma contains molecules, such as oxylipins, which possess cell signaling functions. Several studies have shown that specific molecules in seminal fluid can increase passive diffusion, and cause interactions in the female reproductive tract. This may provoke a cascade of cellular and molecular changes in general health and certain diseases. This study examines the hypothesis that the molecules in seminal fluid are involved in platelet activity. The molecules diffuse through cells and membranes, affecting Hoxa 10, binding ganglioside pathways, and acting over platelet function. When these molecules are at low levels, they may trigger prothrombotic states, explaining the pathophysiology of haemostatic response, such as preeclampsia, and increased risk of cardiovascular disease. PMID- 27372853 TI - The effect of physical exercise on orexigenic and anorexigenic peptides and its role on long-term feeding control. AB - Over the past decades, life-styles changing have led to exacerbated food and caloric intake and a reduction in energy expenditure. Obesity, main outcome of these changes, increases the risk for developing type 2 diabetes, cardiovascular disease and metabolic syndrome, the leading cause of death in adult and middle age population. Body weight and energy homeostasis are maintained via complex interactions between orexigenic and anorexigenic neuropeptides that take place predominantly in the hypothalamus. Overeating may disrupt the mechanisms of feeding control, by decreasing the expression of proopiomelanocortin (POMC) and alpha-melanocyte stimulating hormone (alpha-MSH) and increasing orexigenic neuropeptide Y (NPY) and agouti-related peptide (AgRP), which leads to a disturbance in appetite control and energy balance. Studies have shown that regular physical exercise might decrease body-weight, food intake and improve the metabolic profile, however until the currently there is no consensus about its effects on the expression of orexigenic/anorexigenic neuropeptides expression. Therefore, we propose that the type and length of physical exercise affect POMC/alphaMSH and NPY/AgRP systems differently and plays an important role in feeding behavior. Moreover, based on the present reports, we hypothesize that increased POMC/alphaMSH overcome NPY/AgRP expression decreasing food intake in long term physical exercise and that results in amelioration of several conditions related to overweight and obesity. PMID- 27372854 TI - Oocyte activation and latent HIV-1 reactivation: AMPK as a common mechanism of action linking the beginnings of life and the potential eradication of HIV-1. AB - In all mammalian species studied to date, the initiation of oocyte activation is orchestrated through alterations in intracellular calcium (Ca(2+)) signaling. Upon sperm binding to the oocyte plasma membrane, a sperm-associated phospholipase C (PLC) isoform, PLC zeta (PLCzeta), is released into the oocyte cytoplasm. PLCzeta hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to produce diacylglycerol (DAG), which activates protein kinase C (PKC), and inositol 1,4,5-trisphosphate (IP3), which induces the release of Ca(2+) from endoplasmic reticulum (ER) Ca(2+) stores. Subsequent Ca(2+) oscillations are generated that drive oocyte activation to completion. Ca(2+) ionophores such as ionomycin have been successfully used to induce artificial human oocyte activation, facilitating fertilization during intra-cytoplasmic sperm injection (ICSI) procedures. Early studies have also demonstrated that the PKC activator phorbol 12-myristate 13-acetate (PMA) acts synergistically with Ca(2+) ionophores to induce parthenogenetic activation of mouse oocytes. Interestingly, the Ca(2+) induced signaling cascade characterizing sperm or chemically-induced oocyte activation, i.e. the "shock and live" approach, bears a striking resemblance to the reactivation of latently infected HIV-1 viral reservoirs via the so called "shock and kill" approach, a method currently being pursued to eradicate HIV-1 from infected individuals. PMA and ionomycin combined, used as positive controls in HIV-1 latency reversal studies, have been shown to be extremely efficient in reactivating latent HIV-1 in CD4(+) memory T cells by inducing T cell activation. Similar to oocyte activation, T cell activation by PMA and ionomycin induces an increase in intracellular Ca(2+) concentrations and activation of DAG, PKC, and downstream Ca(2+)-dependent signaling pathways necessary for proviral transcription. Interestingly, AMPK, a master regulator of cell metabolism that is activated thorough the induction of cellular stress (e.g. increase in Ca(2+) concentration, reactive oxygen species generation, increase in AMP/ATP ratio) is essential for oocyte maturation, T cell activation, and mitochondrial function. In addition to the AMPK kinase LKB1, CaMKK2, a Ca(2+)/calmodulin-dependent kinase that also activates AMPK, is present in and activated on T cell activation and is also present in mouse oocytes and persists until the zygote and two-cell stages. It is our hypothesis that AMPK activation represents a central node linking T cell activation-induced latent HIV-1 reactivation and both physiological and artificial oocyte activation. We further propose the novel observation that various compounds that have been shown to reactivate latent HIV-1 (e.g. PMA, ionomycin, metformin, bryostatin, resveratrol, etc.) or activate oocytes (PMA, ionomycin, ethanol, puromycin, etc.) either alone or in combination likely do so via stress-induced activation of AMPK. PMID- 27372855 TI - Responding to the existentials of non-life-threatening chronic conditions. AB - Diagnosis of a major life-threatening illness can prompt a range of existential responses that typically include strong emotions and a reassessment of priorities. What has not attracted attention are the existential responses to being told about less major but permanent medical conditions. A conceptual frame is developed for identifying and speaking about the existential dynamics of permanent change. It introduces two key concepts, finitude and transcendence, and uses them to explain the common sequence of responses first from being told about a chronic condition through to when its presence has become integrated into everyday life. Based on this analysis, a range of recommendations are provided on what types of conversations are helpful through the various stages of adjustment. PMID- 27372856 TI - Home-applied IPL epilation may prevent the problems due to hair follicle in amputees. AB - Amputees may suffer from dermatoses such as folliculitis and pilonidal sinus caused by pressure on the stump in hairy parts of the skin. These conditions commonly cause pain and need treatment that result in abandonment of prosthesis use and disrupt the patient's daily living activities. We believe these conditions may be easily, effectively and cheaply prevented with the use of intense pulsed light technology, which is produced for home epilation. The use of this kind of epilator in the early period post-amputation may prevent the development of folliculitis and pilonidal sinus. This application may also be cost-effective in long term. PMID- 27372857 TI - General vulnerability to stuttering: The experience of stuttering and conditions bringing about invulnerability. AB - General vulnerability to stuttering is the broad awareness of stuttering and the ever-present, experiential sense of a person who stutters (PWS). It is defined by stuttering in all its forms and the awareness of its presence, both in moments of stuttering and moments of perceivably fluent speech. Under the heading of general vulnerability to stuttering is specific vulnerability to stuttering, which includes the actual events of stuttering (i.e., overt symptoms, covert symptoms, subperceptual stuttering, and anticipation of stuttering). The differentiation between the two is that specific vulnerability requires a specific moment of stuttering where general vulnerability does not. PMID- 27372858 TI - Transitionality in addiction: A "temporal continuum" hypotheses involving the aberrant motivation, the hedonic dysregulation, and the aberrant learning. AB - Addiction is a chronic compulsion and relapsing disorder. It involves several brain areas and circuits, which encode vary functions such as reward, motivation, and memory. Drug addiction is defined as a "pathological pattern of use of a substance", characterized by the loss of control on drug-taking-related behaviors, the pursuance of those behaviors even in the presence of negative consequences, and a strong motivated activity to assume substances. Three different theories guide experimental research on drug addiction. Each of these theories consider singles features, such as an aberrant motivation, a hedonic dysregulation, and an aberrant habit learning as the main actor to explain the entire process of the addictive behaviors. The major goal of this study is to present a new hypotheses of transitionality from a controlled use to abuse of addictive substances trough the overview of the three different theories, considering all the single features of each single theory together on the same "temporal continuum" from use to abuse of addictive substances. Recently, it has been suggested that common neural systems may be activated by natural and pharmacological stimuli, raising the hypotheses that binge-eating disorders could be considered as addictive behaviors. The second goal of this study is to present evidences in order to highlight a possible psycho-bio-physiological superimposition between drug and "food addiction". Finally, interesting questions are brought up starting from last findings about a theoretical/psycho-bio physiological superimposition between drug and "food addiction" and their possibly same transitionality along the same "temporal continuum" from use to abuse of addictive substances in order to investigate new therapeutic strategies based on new therapeutic strategies based on the individual moments characterizing the transition from the voluntary intake of substances to the maladaptive addictive behavior. PMID- 27372859 TI - Is prostate cancer screening responsible for the negative results of prostate cancer treatment trials? AB - Clinical guidelines continue to move away from routine prostate specific antigen screening (PSA), once a widespread medical practice. A curious difference exists between early prostate cancer and early breast cancer. While randomized trials of therapy in early breast cancer continue to show overall survival benefit, this is not the case in prostate cancer, where prostatectomy was no better than observation in a recent trial, and where early androgen deprivation is no better than late androgen deprivation. Here, I make the case that prostate cancer screening contributes so greatly to over diagnosis that even treatment trials yield null results due to contamination with non-life threatening disease. PMID- 27372860 TI - Microsatellite instability as a predictive factor for immunotherapy in malignant melanoma. AB - Immunotherapy has attracted attention as a novel treatment modality for malignant melanoma. Although the use of immunotherapy in metastatic melanoma has shown promising results, there remains a lack of predictive biomarkers indicating treatment benefit from immunotherapy. There is growing evidence suggesting that microsatellite instability (MSI) as a product of DNA mismatch repair deficiency, may be one of possible predictive markers in malignant melanoma. It has been proposed that the immunogenicity of some tumors might be determined by mutational heterogeneity and could be the key to the success of immune therapies. This is also supported by the fact that tumors with the highest amount of somatic mutations, such as malignant melanoma have showed positive results with immune checkpoint inhibitors. There are promising data regarding the association between MSI status and immunogenicity from studies with colorectal cancer, where MSI is linked to improved prognosis compared to microsatellite stable cancers. MSI in colon cancer is linked to a significant increase of immunocompetent cells responsible for the antitumor activity - CD3(+), CD8(+), CD45RO(+), and T-bet(+) lymphocytes and decrease of inhibition factors such as Foxp3, IL-6, IL-17, and TGF-beta. On the other hand, taking into account the progression-dependent accumulation of somatic mutations in MSI tumors and consequent high levels of neo antigens, the possible drug resistance of MSI tumors to traditional treatment, and the presence of inhibition checkpoints within the MSI tumors, there is a solid rationale for the use of novel therapeutic strategies such as immunotherapy in MSI melanomas. We presume that the MSI phenotype in malignant melanoma might be helpful to identify patients, who would be more likely to profit from immunotherapy than from conventional therapy. PMID- 27372861 TI - Targeting the ecology within: The role of the gut-brain axis and human microbiota in drug addiction. AB - Despite major advances in our understanding of the brain using traditional neuroscience, reliable and efficacious treatments for drug addiction have remained elusive. Hence, the time has come to utilize novel approaches, particularly those drawing upon contemporary advances in fields outside of established neuroscience and psychiatry. Put another way, the time has come for a paradigm shift in the addiction sciences. Apropos, a revolution in the area of human health is underway, which is occurring at the nexus between enteric microbiology and neuroscience. It has become increasingly clear that the human microbiota (the vast ecology of bacteria residing within the human organism), plays an important role in health and disease. This is not surprising, as it has been estimated that bacteria living in the human body (approximately 1kg of mass, roughly equivalent to that of the human brain) outnumber human cells 10 to 1. While advances in the understanding of the role of microbiota in other areas of human health have yielded intriguing results (e.g., Clostridium difficile, irritable bowel syndrome, autism, etc.), to date, no systematic programs of research have examined the role of microbiota in drug addiction. The current hypothesis, therefore, is that gut dysbiosis plays a key role in addictive disorders. In the context of this hypothesis, this paper provides a rationale for future research to target the "gut-brain axis" in addiction. A brief background of the gut-brain axis is provided, along with a series of hypothesis-driven ideas outlining potential treatments for addiction via manipulations of the "ecology within." PMID- 27372862 TI - Role of reduced insulin-stimulated bone blood flow in the pathogenesis of metabolic insulin resistance and diabetic bone fragility. AB - Worldwide, 387 million adults live with type 2 diabetes (T2D) and an additional 205 million cases are projected by 2035. Because T2D has numerous complications, there is significant morbidity and mortality associated with the disease. Identification of early events in the pathogenesis of insulin resistance and T2D might lead to more effective treatments that would mitigate health and monetary costs. Here, we present our hypothesis that impaired bone blood flow is an early event in the pathogenesis of whole-body metabolic insulin resistance that ultimately leads to T2D. Two recent developments in different fields form the basis for this hypothesis. First, reduced vascular function has been identified as an early event in the development of T2D. In particular, before the onset of tissue or whole body metabolic insulin resistance, insulin-stimulated, endothelium-mediated skeletal muscle blood flow is impaired. Insulin resistance of the vascular endothelium reduces delivery of insulin and glucose to skeletal muscle, which leads to tissue and whole-body metabolic insulin resistance. Second is the paradigm-shifting discovery that the skeleton has an endocrine function that is essential for maintenance of whole-body glucose homeostasis. Specifically, in response to insulin signaling, osteoblasts secret osteocalcin, which stimulates pancreatic insulin production and enhances insulin sensitivity in skeletal muscle, adipose, and liver. Furthermore, the skeleton is not metabolically inert, but contributes to whole-body glucose utilization, consuming 20% that of skeletal muscle and 50% that of white adipose tissue. Without insulin signaling or without osteocalcin activity, experimental animals become hyperglycemic and insulin resistant. Currently, it is not known if insulin stimulated, endothelium-mediated blood flow to bone plays a role in the development of whole body metabolic insulin resistance. We hypothesize that it is a key, early event. Microvascular dysfunction is a primary cause of diabetic nephropathy, retinopathy and neuropathy and poor bone blood flow is associated with bone loss. Therefore, we also hypothesize that dysfunction of the bone vascular endothelium contributes to the bone fragility observed in T2D. The most important consequence of our-dual hypothesis is the public health significance. Namely, identification of the proximal cause of T2D and associated bone complications allows pursuit of the appropriate therapeutic target to treat and prevent T2D. If our hypothesis that reduced bone blood flow is an early event in the pathogenesis of T2D and diabetic bone fragility is correct, then the endothelium of the bone vasculature should be a therapeutic target. PMID- 27372863 TI - Fructose surges damage hepatic adenosyl-monophosphate-dependent kinase and lead to increased lipogenesis and hepatic insulin resistance. AB - Fructose may be a key contributor to the biochemical alterations which promote the metabolic syndrome (MetS), non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM): (a) its consumption in all forms but especially in liquid form has much increased alongside with incidence of MetS conditions; (b) it is metabolized almost exclusively in the liver, where it stimulates de novo lipogenesis to drive hepatic triglyceride (TG) synthesis which (c) contributes to hepatic insulin resistance and NAFLD (Lustig et al., 2015; Weiss et al., 2013; Lim et al., 2010; Schwarzet al., 2015; Stanhope et al., 2009, 2013) [1-6]. The specifics of fructose metabolism and its main location in the liver serve to explain many of the possible mechanisms involved. It also opens questions, as the consequences of large increases in fructose flux to the liver may wreak havoc with the regulation of metabolism and would produce two opposite effects (inhibition and activation of AMP dependent kinase-AMPK) that would tend to cancel each other. We posit that (1) surges of fructose in the portal vein lead to increased unregulated flux to trioses accompanied by unavoidable methylglyoxal (MG) production, (2) the new, sudden flux exerts carbonyl stress on the three arginines on the gamma subunits AMP binding site of AMPK, irreversible blocking some of the enzyme molecules to allosteric modulation, (3) this explains why, even when fructose quick phosphorylation increases AMP and should therefore activate AMPK, the effects of fructose are compatible with inactivation of AMPK, which then solves the apparent metabolic paradox. We put forward the hypothesis that fructose loads, via the increase in MG flux worsens the fructose-driven metabolic disturbances that lead to unrestricted de novo lipogenesis, fatty liver and hepatic insulin resistance. It does so via the silencing of AMPK. Our hypothesis is testable and if proven correct will shed some further light on fructose metabolism in the liver. It will also open new roads in glycation research, as modulation of MG catabolism may be a way to dampen the damage. Research on this area may have important therapeutic potential, e.g., more momentum to find new and improved carbonyl quenchers, new insights on the action of metformin, more evidence for the role of GAPDH inactivation due to mitochondrial overload in diabetes complications. AMPK plays a central role in metabolism, and its function varies in different tissues. For that reason, synthetic activators will always stumble with unwanted or unpredictable effects. Preventing MG damage on the protein could be a safer therapeutic avenue. PMID- 27372864 TI - A re-examination of the role of the acute phase protein response in innate cancer defence. AB - Anti-cancer host defense mechanisms are traditionally considered to consist of tumor suppressor genes and immune surveillance by cells of the innate and adaptive immune systems. However, there is mounting evidence that components of the acute phase protein response (APPR), and, in particular, certain cationic host defense peptides (HDPs), also contribute to anti-cancer host defense. In a number of in vitro studies, certain HDPs have been shown to be cytotoxic to tumor cells either directly through cancer cell membrane destabilization and lysis or through the initiation of apoptosis in the cancer cell. In addition, many cancer cells elaborate the pro-inflammatory cytokine interleukin-6, which in turn produces an APPR that involves the release of HDPs. It is therefore possible that the release of pro-inflammatory cytokines by cancer cells initiates a poorly understood anti-tumor response by the host that involves HDP induction. We hypothesize that the APPR may form an important anti-cancer host defense response. This may be an important consideration in light of cancer treatments designed to decrease systemic inflammation. Blunting of the anti-cancer effect of the APPR may also contribute to the increased cancer rates seen in chronic immunosuppressive states. PMID- 27372865 TI - Therapeutic effect of recombinant lentiviral vector containing succinate dehydrogenase iron-sulfur protein on the treatment of experimental autoimmunity myocarditis. AB - Cardiac autoimmune reaction takes part in myocarditis, dilated cardiomyopathy and heart failure. Existing literature has confirmed that the occurrence of cardiomyopathy belongs to mitochondrial diseases and is related to the oxidative respiratory chain subunit. The special structure of iron-sulfur protein (ISP) is responsible for the oxidative stress in oxidative phosphorylation, which is also a target that is easily attacked by various damage factors. Using gene therapy technology to restore succinate dehydrogenase iron-sulfur protein (SDISP) function- and thus resume myocardial mitochondria function and myocardial function is hypothesized to alleviate the experimental autoimmunity myocarditis (EAM). PMID- 27372866 TI - A hypothesis of target cell formation in sickle cell disease. AB - A fraction of erythrocytes appear as target cells in stained blood smears in sickle cell disease, due to a inheritance of the hemoglobin variant Hb S, polymerizing upon deoxygenation. These cells appear in a three dimension as thin cups. A process of their formation in this disease is proposed based on a band 3 based mechanism of the erythrocyte shape control, able to explain the erythrocyte echinocytosis by glucose depletion. It indicates that their formation is due to a stomatocytogenic slow outward transport of the dibasic form of endogenous Pi with an H(+) by band 3, promoted by the decrease of the Donnan ratio, which decreases cell pH and volume, attributed by a decrease of cell KCl concentration by the higher efflux of K(+)Cl(-) cotransport and Ca(2+) activation of the Gardos channel. Its implications are briefly discussed with respect to target cells per se, target cell formation in other hemoglobinopathies, acquired and inherited disorders of the lipid metabolism and dehydrated hereditary stomatocytosis as well as a stomatocyte presence in a double heterozygote of Hb S and Hb C and of an involvement of the process of target cell formation in acanthocytosis in acquired and inherited disorders. PMID- 27372867 TI - Ageing is a process where the growth effect of neuronal noradrenaline changes progressively in favour of the flow mediated, neurodegenerative and inflammatory effect of plasma noradrenaline. AB - The noradrenaline stimulus has two components, one excitor, the other inhibitory. Neuronal noradrenaline is the excitor component and plasma noradrenaline is the inhibitory. The balance of effect between the two, the noradrenergic balance, is the controlled variable of the sympathetic system and determines the effect of noradrenaline. Neuronal noradrenaline stimulates tissues by diffusion from their sympathetic nerve endings, plasma noradrenaline does so by diffusion from their microcirculations. Changes in microcirculatory flow, by altering the flow mediated effect of plasma noradrenaline, are mainly responsible for altering the noradrenergic balance in the peripheral tissues; changes in CSF flow are speculated to be mainly responsible for doing the same in the brain, by altering the balance between synaptic noradrenaline in the brain and nonsynaptic noradrenaline in the subarachnoid CSF. When plasma noradrenaline alters the noradrenergic balance it triggers afferent sympathetic activity that alerts hypothalamic neurons to the event and they restore the balance and tissue homeostasis, within milliseconds, by adjusting the level of efferent sympathetic activity they project back to the affected tissue. Because the restoration is so rapid the effect of plasma noradrenaline is normally unobservable and dismissed as not having occurred. Because the hypothalamus is not involved with the responses of isolated canine lateral saphenous vein segments to noradrenaline, the effects of plasma noradrenaline in that preparation are not countered by reactive efferent activity and, consequently, are readily apparent in it. Quantitatively, they have been found to be a function of microcirculatory flow and noradrenaline concentration and, qualitatively, to be inhibitory, dilator, pro inflammatory and neurodegenerative. In life, due to a progressive increase in plasma noradrenaline concentration and, more so, in microcirculatory flow, the noradrenergic balance moves progressively in favour of the neurodegenerative and inflammatory effects of plasma noradrenaline. These observations are the basis of an hypothesis that ageing is caused by a genetically programmed shift in balance away from the growth and anti-inflammatory effects of neuronal noradrenaline, early in life, towards the neurodegenerative and pro-inflammatory effects of plasma noradrenalin, later in life. Death is believed to occur when plasma noradrenaline has damaged the structure of the sympathetic system so much that it can no longer create the minimum quantity of neurotransmitter needed to maintain the level of noradrenergic balance and homeostasis necessary for life. PMID- 27372868 TI - Chemogenetic approach to model hypofrontality. AB - Clinical evidence suggests that the prefrontal cortex (PFC) is hypofunctional in disorders including schizophrenia, drug addiction, and attention deficit/hyperactivity disorder (ADHD). In schizophrenia, hypofrontality has been further suggested to cause both the negative and cognitive symptoms, and overactivity of dopamine neurons that project to subcortical areas. The latter may contribute to the development of positive symptoms of the disorder. Nevertheless, what causes hypofrontality and how it alters dopamine transmission in subcortical structures remain unclear due, in part, to the difficulty in modeling hypofrontality using previous techniques (e.g. PFC lesioning, focal cooling, repeated treatment with psychotomimetic drugs). We propose that the use of designer receptors exclusively activated by designer drugs (DREADDs) chemogenetic technique will allow precise interrogations of PFC functions. Combined with electrophysiological recordings, we can investigate the effects of PFC hypofunction on activity of dopamine neurons. Importantly, from a drug target discovery perspective, the use of DREADDs will enable us to examine whether chemogenetically enhancing PFC activity will reverse the behavioral abnormalities associated with PFC hypofunction and dopamine neuron overactivity, and also explore druggable targets for the treatment of schizophrenia and other disorders associated with abnormalities via modulation of the G-protein coupled receptor signaling pathway. In conclusion, the use of the DREADDs technique has several advantages over other previously employed strategies to simulate PFC hypofunction not only in terms of disease modeling but also from the viewpoint of drug target discovery. PMID- 27372869 TI - Inflammasome activation by cell volume regulation and inflammation-associated hyponatremia: A vicious cycle. AB - Inflammasomes are caspase-1-activating molecular platforms that produce active interleukin (IL)-1beta and are implicated in various central nervous system (CNS) diseases. These multi-protein complexes can be activated by exposure of cells to low osmolality. The inflammasome nucleotide-binding and oligomerization domain like receptor pyrin domain-containing protein 3 (NLRP3) is hereby the main sensor of cellular osmolality. IL-1beta was found to stimulate the secretion of antidiuretic hormone (ADH) from the posterior pituitary gland either by action of prostaglandins or indirectly by causing the release of IL-6. Based on these findings, we hypothesize that the hyponatremia caused by a wide range of CNS diseases is able to induce significant cell swelling with induction of a hyposmotic intracellular environment, which activates the NLRP3 inflammasome, causing the release of IL-1beta and induced by IL-1beta, IL-6, which increases the production of ADH that leads to more profound hyponatremia. Supportive evidence for this hypothesis is the finding that IL-1 injection can induce ADH release and hyposmotic effect of ADH induced hyponatremia can, via the mechanical effect of cell swelling, activate transient receptor potential channels, which via transforming growth factor beta-activated kinase 1 activate NLRP3. Implications of this hypothesis, if confirmed, would include that hyponatremia can be exacerbated through this vicious cycle but also that the inflammasomes are key mediators of this process. Confirmation of this hypothesis would have implications for prevention and clinical management of changes in patients sodium levels related to syndrome of inappropriate antidiuretic hormone secretion (SIADH) with interventions targeting inflammatory mediator production and function of inflammasomes with the potential of prevention of permanent brain damage in a wide range of CNS diseases. PMID- 27372870 TI - Sexual arousal and rhythmic synchronization: A possible effect of vasopressin. AB - Music is ubiquitous. Yet, its biological relevance is still an ongoing debate. Supporting the view that music had an ancestral role in courtship displays, a pilot study presented here provides preliminary evidence on the link between music and sexual selection. The underlying hypothesis is based on the fact that the sexually dimorphic neuropeptide vasopressin has its receptors in the part of the brain involved in music and dance performance (the basal ganglia), and its concentrations rise during sexual arousal in men. In addition, music, dance, and courtship phenotypes seem to be in part regulated by vasopressin and its genes. Hence, to test this hypothesis, a rhythmic synchronization task was employed here on one male subject during sexual arousal. Results revealed a significant effect of sexual arousal on rhythm synchronization. This is the first report that empirically supports the hypothesis on the role of music in sexual selection. Further studies are clearly required. PMID- 27372871 TI - Anthropogenic and temporal components in a complex trigger of type 1 diabetes suggest the active participation of antipyretics. AB - Tremendous efforts in research without a conclusion on the cause of type 1 diabetes allow the presumption that there is still a blind spot in the development of T1D that is not covered by current hypotheses. The review of geographical knowledge suggests that there is a well-expressed anthropogenic element within the complex environmental trigger of T1D. On the other hand, the initiation of T1D's directed autoimmunity is temporally related to the organism's immune response, induced by entero-viruses, most expectedly. Consequently, the searched for anthropogenic environmental factor is a player temporally linked to enteroviral infections. This paper discusses the participation of antipyretic medicines, and especially paracetamol, with a whole century's history of growing sales and popularity, including indirect influence through phenacetin during the first half of the 20th century. As proposed by several independent studies, the use of pharmaceuticals to reduce fever may counteract with the protective features of the immune system and create favourable conditions for a virus to spread within the organism and damage specific tissue. A preliminary comparison of paracetamol sales with the incidence of T1D data in Lithuania and the other countries in the North-eastern Baltic region supports this hypothesis. PMID- 27372872 TI - A systemic evolutionary approach to cancer: Hepatocarcinogenesis as a paradigm. AB - The systemic evolutionary theory of cancer pathogenesis posits that cancer is generated by the de-emergence of the eukaryotic cell system and by the re emergence of its archaea (genetic material and cytoplasm) and prokaryotic (mitochondria) subsystems with an uncoordinated behavior. This decreased coordination can be caused by a change in the organization of the eukaryote environment (mainly chronic inflammation), damage to mitochondrial DNA and/or to its membrane composition by many agents (e.g. viruses, chemicals, hydrogenated fatty acids in foods) or damage to nuclear DNA that controls mitochondrial energy production or metabolic pathways, including glycolysis. Here, we postulate that the two subsystems (the evolutionarily inherited archaea and the prokaryote) in a eukaryotic differentiated cell are well integrated, and produce the amount of clean energy that is constantly required to maintain the differentiated status. Conversely, when protracted injuries impair cell or tissue organization, the amount of energy necessary to maintain cell differentiation can be restricted, and this may cause gradual de-differentiation of the eukaryotic cell over time. In cirrhotic liver, for example, this process can be favored by reduced oxygen availability to the organ due to an altered vasculature and the fibrotic barrier caused by the disease. Thus, hepatocarcinogenesis is an ideal example to support our hypothesis. When cancer arises, the pre-eukaryote subsystems become predominant, as shown by the metabolic alterations of cancer cells (anaerobic glycolysis and glutamine utilization), and by their capacity for proliferation and invasion, resembling the primitive symbiotic components of the eukaryotic cell. PMID- 27372873 TI - CTC immune escape mediated by PD-L1. AB - Breast cancer is the most common malignant tumor in women around the world. Most breast cancer-related deaths are from CTC (circulating tumor cells) metastasis. CTC is associated with the breast cancer patients' prognosis. But recently, circulating clusters were found and its metastasis and tumor formation ability is 23-50 times as CTC. However, its mechanism has not been clarified. These days, researchers have successfully completed CTC cluster separation, CTC cell culture, and PD-L1 was found to be related with histological grading of tumor. Meanwhile, the high expression of PD-L1 in CTC surface has also been reported. Since PD-L1 can mediate Treg to play the role of immunosuppression, we propose that CTC with positive PD-L1 is easier to connect PD-L1, immune cells (Treg regulatory T cells, MDSC bone marrow inhibitory cells) and CK cytokines etc. On one hand, Treg cells can protect CTC from being attacked by the immune system through the immunosuppression, on the other hand, they can weaken CTL killing ability and trigger more MDSC. Finally, CTC formed the metastatic lesion. PMID- 27372874 TI - The potential synergism by combining external counterpulsation with intermittent theta burst stimulation in post-stroke motor function recovery. AB - Upper limb weakness and incoordination is a common disability following ischemic stroke. Previous studies have showed that the single application of external counterpulsation (ECP) and intermittent theta burst stimulation (iTBS) can effectively enhance the cortical motor excitability and facilitate recovery. However, it remains uncertain if sequential application of these therapies would further augment the recovery. We hypothesize a synergistic effect of ECP followed by iTBS to upper limb function may happen through improvements in both cerebral perfusion and neuron excitability. PMID- 27372875 TI - Adipose-derived stem cells: A novel source of parathyroid cells for treatment of hypoparathyroidism. AB - Hypoparathyroidism is characterized by decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH), which can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany, and several other symptoms. Severe hypocalcemia is a life-threatening condition. At present, both medical and surgical treatments are offered to improve the blood calcium, but they are not a cure. Adipose-derived stem cells (ADSCs), derived from the adipose tissue, are confirmed to be multipotent with adipogenic, chondrogenic, neurogenic, myogenic and osteogenic capabilities. Our hypothesis is that human ADSCs in culture can be differentiated into parathyroid cells, and used to reconstitute function. PMID- 27372876 TI - A specific hygiene hypothesis. AB - Allergic diseases have reached epidemic proportions in Western populations in the last several decades. The hygiene hypothesis proposed more than twenty years ago has helped us to understand the epidemic and has been verified with numerous studies. However, translational measures deduced from these studies to prevent allergic diseases have not proven effective. Recent studies on immigrants' allergies and any potential association between oral infection and allergic diseases prompt me to propose a specific hygiene hypothesis to explain how oral hygiene practices might have contributed to the uprising of hay fever, the most common allergic disease. The historic oral hygiene level in US is closely associated with the emerging allergic epidemic. Future studies to test the hypothesis are needed and verification of the hypothesis can potentially yield highly effective measures to prevent allergic diseases. PMID- 27372877 TI - Anabolic androgenic steroid-induced hepatotoxicity. AB - Anabolic androgenic steroids (AAS) have been abused for decades by both professional and amateur athletes in order to improve physical performance or muscle mass. AAS abuse can cause adverse effects, among which are hepatotoxic effects. These effects include cholestatic icterus and possibly peliosis hepatis and hepatocellular carcinoma or adenoma. In particular, 17alpha-alkylated AAS appear to be hepatotoxic, whereas nonalkylated AAS appear not to be. The 17alpha alkyl substitution retards hepatic metabolism of the AAS rendering it orally bioavailable. The mechanism responsible for the hepatotoxicity induced by 17alpha alkylated AAS remains poorly understood. However, oxidative stress has been repeatedly shown to be associated with it. In this manuscript we present a hypothesis which describes a potential mechanism responsible for AAS-induced hepatotoxicity, based on several observations from the literature which suggest oxidative stress being a causal factor. PMID- 27372878 TI - Is age-related failure of metabolic reprogramming a principal mediator in idiopathic Parkinson's disease? Implications for treatment and inverse cancer risk. AB - Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder characterized by selective degeneration of the substantia nigra pars compacta (SNc), dorsal motor nucleus of the vagus and other vulnerable nervous system regions characterized by extensive axonal arborization and intense energy requirements. Systemic age-related depression of mitochondrial function, oxidative phosphorylation (OXPHOS) and depressed expression of genes supporting energy homeostasis is more severe in IPD than normal aging such that energy supply may exceed regional demand. In IPD, the overall risk of malignancy is reduced. Cancer is a collection of proliferative diseases marked by malignant transformation, dysregulated mitosis, invasion and metastasis. Many cancers demonstrate normal mitochondrial function, preserved OXPHOS, competent mechanisms of energy homeostasis, and metabolic reprogramming capacities that are lacking in IPD. Metabolic reprogramming adjusts OXPHOS and glycolytic pathways in response to changing metabolic needs. These opposite metabolic features form the basis of a two component hypothesis. First, that depressed mitochondrial function, OXPHOS deficiency and impaired metabolic reprogramming contribute to focal energy failure, neurodegeneration and disease expression in IPD. Second, that the same systemic metabolic deficits inhibit development and proliferation of malignancies in IPD. Studies of mitochondrial aging, familial PD (FPD), the lysosomal storage disorder, Gaucher's disease, Parkinson's disease cybrids, the mitochondrial cytopathies, and disease-related metabolic reprogramming both in IPD and cancer provide support for this model. PMID- 27372879 TI - Possible role of Epoxyeicosatrienoic acid in prevention of oxidative stress mediated neuroinflammation in Parkinson disorders. AB - Parkinson's disease (PD) is a multifactorial neurodegenerative disease involving oxidative stress, neuroinflammation and apoptosis. Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites and they play a role in cytoprotection by modulating various cell signaling pathways. This cytoprotective role of EETs are well established in cerebral stroke, cardiac failure, and hypertension, and it is due to their ability to attenuate oxidative stress, endoplasmic reticulum stress, inflammation, caspase activation and apoptosis. The actions of EETs in brain closely parallel the effects which is observed in the peripheral tissues. Since many of these effects could potentially contribute to neuroprotection, EETs are, therefore, one of the potential therapeutic candidates in PD. Therefore, by increasing the half life of endogenous EETs in vivo via inhibition of sEH, its metabolizing enzyme can, therefore, constitutes an important therapeutic strategy in PD. PMID- 27372880 TI - Pathogenesis of Rushton bodies: A novel hypothesis. AB - Rushton bodies (RBs) are one of the characteristic features seen in the epithelial lining of odontogenic cysts mainly radicular, dentigerous and odontogenic keratocyst. It has two different histo-morphological appearances; granular and homogeneous. Although widely investigated, the exact pathogenesis and histogenesis of RBs is still an enigma. Many hypotheses were made in the literature but none has explained conceivably the two histo-morphological appearances of RBs and their association with inflammation. In the present paper the various pathogenesis for the formation of RBs proposed till date are discussed along with proposal for a novel hypothesis. The given hypothesis is mainly related to inflammation and its effect on pore size of basement membrane of odontogenic cystic epithelium. It explains RBs association with inflammation as well as existence of two histo-morphological appearances. The proposed hypothesis also justifies the RB's presence inside the lining epithelium of odontogenic cyst despite its hematogenous origin. Future studies are advocated for isolating RBs using laser capture microdissection and subsequent biochemical, histochemical and electron microscopic analysis to substantiate the proposed hypothesis. PMID- 27372881 TI - The predictive validity of common risk assessment tools in men with intellectual disabilities and problematic sexual behaviors. AB - This CIHR-funded study examined whether certain current risk assessment tools were effective in appraising risk of recidivism in a sample of sex offenders with intellectual disabilities (ID). Fifty men with ID who had engaged in problematic sexual behavior (PSB) were followed for an average of 2.5 years. Recidivism was defined and measured as any illegal or problematic behavior, as well as any problematic but not necessarily illegal behavior. At the beginning of the study, each participant was rated on two risk assessment tools: the Violence Risk Appraisal Guide (VRAG) and the Sex Offender Risk Appraisal Guide (SORAG). During each month of follow-up, participants were also rated on the Short-Dynamic Risk Scale (SDRS), an assessment tool intended to measure the risk of future problematic behaviors. Data was analyzed using t-tests, Cohen's d and area under the curve (AUC) to test predictive validity of the assessment tools. Using the AUC, results showed that the VRAG was predictive of sexual (AUC=0.74), sexual and/or violent (AUC=0.71) and of any criminally chargeable event (AUC=0.69). The SORAG was only significantly predictive of sexual events (AUC=0.70) and the SDRS was predictive of violent events (AUC=0.71). The t-test and Cohen's d analyses, which are less robust to deviations from the assumptions of normal and continuous distribution than AUC, did not yield significant results in each category, and therefore, while the results of this study suggest that the VRAG and the SORAG may be effective tools in measuring the short term risk of sexual recidivism; and the VRAG and SDRS may be effective tools in appraising long term risk of sexual and/or violent recidivism in this population, it should be used with caution. Regardless of the assessment tool used, risk assessments should take into account the differences between sex offenders with and without ID to ensure effective measurement. PMID- 27372882 TI - The experiences and support needs of people with intellectual disabilities who identify as LGBT: A review of the literature. AB - BACKGROUND: People who identify as lesbian, gay, bisexual and transgender (LGBT) can face many challenges in society including accessing education, care and support appropriate to individual needs. However, there is a growing and evolving evidence base about the specific needs of people with intellectual disabilities (ID) in this regard. AIMS: The aim of this review was to explore the experiences of people with ID who identified as LGBT through an examination of studies that addressed their views and highlighted specific issues, concerns and service responses. METHODS AND PROCEDURES: A comprehensive search of relevant databases from February 1995 to February 2015 was conducted. Studies were identified that met specific criteria that included: empirical peer reviewed studies, the use of recognised research methods and focused on people with ID whom identified as LGBT. The search yielded 161 papers in total. The search was narrowed and 37 papers were screened using rigorous inclusion and exclusion criteria. Finally, 14 papers were considered suitable for the review. OUTCOMES AND RESULTS: The data were analysed and key themes identified that included accessing health services, gender and sexual identity, attitudes of people with ID regarding their LGBT status, and education, supports and therapeutic interventions. CONCLUSIONS AND IMPLICATIONS: There is a need for service providers and carers to be more responsive to the concerns of people with ID who identify as LGBT to improve their health and well-being by reducing stigma and discrimination and by increasing awareness of their care and support needs. The implications are discussed in terms of policy, education, research and practice developments. PMID- 27372883 TI - Sponsorship of junior sport development programs in Australia. AB - OBJECTIVE: This study investigated the nature and extent of unhealthy food, beverage, alcohol and gambling sponsors of children's sport development programs. METHODS: Websites of junior development sport programs (n=56) associated with sporting organisations that received funding from the Australian Sporting Commission were analysed. Sponsors were considered unhealthy if they were alcohol or gambling companies or sold food and/or beverages that failed independent nutrition criteria. The websites of the sport development programs were also analysed for types of promotion. RESULTS: There were 246 sponsors identified. Eleven (4.5%) sponsors were food, beverage, alcohol or gambling companies of which 10 (91%) were unhealthy. Surf Lifesaving (n=4) and athletics (n=3) websites had the highest number of unhealthy sponsors. Promotions associated with unhealthy sponsorship included logo placement on homepages (100%), naming rights (31%), logo on sport uniforms (27%) and branded participant packs (31%). CONCLUSIONS: The majority of food and beverage company sponsors in sport development programs are companies associated with unhealthy products. Two websites hosting junior development program information included an alcohol company sponsor and a gambling company sponsor. IMPLICATIONS: Unhealthy product sponsorship of children's sport should be addressed as part of a comprehensive regulation designed to reduce exposure to marketing of unhealthy foods. PMID- 27372884 TI - Electrophysiological properties of lumbosacral primary afferent neurons innervating urothelial and non-urothelial layers of mouse urinary bladder. AB - Pelvic nerve (PN) bladder primary afferent neurons were retrogradely labeled by intraparenchymal (IPar) microinjection of fluorescent tracer or intravesical (IVes) infusion of tracer into the bladder lumen. IPar and IVes techniques labeled two distinct populations of PN bladder neurons differentiated on the basis of dorsal root ganglion (DRG) soma labeling, dye distribution within the bladder, and intrinsic electrophysiological properties. IPar (Fast blue)- and IVes (DiI)-labeled neurons accounted for 91.5% (378.3+/-32.3) and 8% (33.0+/ 26.0) of all labeled neurons, respectively (p<0.01), with only 2.0+/-1.2 neurons labeled by both techniques. When dyes were switched, IPar (DiI)- and IVes (Fast blue) labeled neurons accounted for 77.6% (103.0+/-25.8) and 22.4% (29.8+/-10.5), respectively (P<0.05), with 6.0+/-1.5 double-labeled neurons. Following IPar labeling, DiI was distributed throughout non-urothelial layers of the bladder. In contrast, dye was contained within the urothelium and occasionally the submucosa after IVes labeling. Electrophysiological properties of DiI-labeled IPar and IVes DRG neurons were characterized by whole-mount, in situ patch-clamp recordings. IPar- and IVes-labeled neurons differed significantly with respect to rheobase, input resistance, membrane capacitance, amplitude of inactivating and sustained K(+) currents, and rebound action potential firing, suggesting that the IVes population is more excitable. This study is the first to demonstrate that IVes labeling is a minimally invasive approach for retrograde labeling of PN bladder afferent neurons, to selectively identify urothelial versus non-urothelial bladder DRG neurons, and to elucidate electrophysiological properties of urothelial and non-urothelial afferents in an intact DRG soma preparation. PMID- 27372885 TI - Meta-analysis of the association between serum iron levels and Parkinson's disease: Evidence from 11 publications. AB - BACKGROUND: There is no consensus on the serum iron levels and Parkinson's disease (PD). The aim of this study is to conduct a systematic review and meta analysis to analyse the relationship between serum iron levels and PD risk. METHODS: We searched the databases of PubMed, Web of knowledge, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and China Biology Medical literature to assess the association between serum iron levels and PD risk. Standardized mean differences (SMD) and 95% confidence intervals (CI) with random-effect model were used to combine the results. RESULTS: Eleven related articles met our selection criteria and contained a total of 829PD patients and 1219 healthy controls. Our meta-analysis results revealed that the serum iron levels in PD patients were significantly higher than those in healthy controls (SMD=0.27, 95% CI=0.18, 0.37, P<0.001). Subgroup analysis by ethnicity showed that the serum iron levels in PD patients were significantly higher than controls both in Asian populations and European populations. Significant associations were also found in prospective studies and case-control studies. CONCLUSIONS: Our meta-analysis showed strong evidence that a significantly higher serum iron levels are present in PD patients when compared to the healthy controls. PMID- 27372886 TI - Britain's vote to leave the EU-what now for health? PMID- 27372887 TI - Bioactive lipids as modulators of immunity, inflammation and emotions. AB - Lipids are not only constituents of cellular membranes but also key signaling mediators, thus acting as 'bioactive lipids'. Among the prominent roles exerted by bioactive lipids are immune regulation, inflammation and maintenance of homeostasis. Accumulated evidence indicates the existence of a bidirectional relationship between immune and nervous systems, whereby inflammatory mediators can directly modulate emotions that, in turn, can strongly influence immune responses, thus affecting health. This review summarizes current knowledge on the ability of several families of bioactive lipids to regulate immunity and inflammation (through pro-inflammatory or anti-inflammatory effects), as well as to control emotions and mood-related manifestations, advocating these substances as an attractive interface between 'mind' and 'body', and as a potential target to treat inflammatory/immune-mediated mood disorders. PMID- 27372888 TI - Relation of Periodontitis to Risk of Cardiovascular and All-Cause Mortality (from a Danish Nationwide Cohort Study). AB - Periodontitis and atherosclerosis are highly prevalent chronic inflammatory diseases, and it has been suggested that periodontitis is an independent risk factor of cardiovascular disease (CVD) and that a causal link may exist between the 2 diseases. Using Danish national registers, we identified a nationwide cohort of 17,691 patients who received a hospital diagnosis of periodontitis within a 15-year period and matched them with 83,003 controls from the general population. We performed Poisson regression analysis to determine crude and adjusted incidence rate ratios of myocardial infarction, ischemic stroke, cardiovascular death, major adverse cardiovascular events, and all-cause mortality. The results showed that patients with periodontitis were at higher risk of all examined end points. The findings remained significant after adjustment for increased baseline co-morbidity in periodontitis patients compared with controls, for example, with adjusted incidence rate ratio 2.02 (95% CI 1.87 to 2.18) for cardiovascular death and 2.70 (95% CI 2.60 to 2.81) for all-cause mortality. Patients with a hospital diagnosis of periodontitis have a high burden of co-morbidity and an increased risk of CVD and all-cause mortality. In conclusion, our results support that periodontitis may be an independent risk factor for CVD. PMID- 27372889 TI - In vitro characterisation of fresh and frozen sex-sorted bull spermatozoa. AB - This study sought to compare the in vitro characteristics of fresh and frozen non sorted (NS) and sex-sorted (SS) bull spermatozoa. Experiment 1: Holstein-Friesian ejaculates (n=10 bulls) were split across four treatments and processed: (1) NS fresh at 3*106 spermatozoa, (2) X-SS frozen at 2*106 spermatozoa, (3) X-SS fresh at 2*106 spermatozoa and (4) X-SS fresh at 1*106 spermatozoa. NS frozen controls of 20*106 spermatozoa per straw were sourced from previously frozen ejaculates (n=3 bulls). Experiment 2: Aberdeen Angus ejaculates (n=4 bulls) were split across four treatments and processed as: (1) NS fresh 3*106 spermatozoa, (2) Y-SS fresh at 1*106 spermatozoa, (3) Y-SS fresh at 2*106 spermatozoa and (4) X-SS fresh at 2*106 spermatozoa. Controls were sourced as per Experiment 1. In vitro assessments for progressive linear motility, acrosomal status and oxidative stress were carried out on Days 1, 2 and 3 after sorting (Day 0=day of sorting. In both experiments SS fresh treatments had higher levels of agglutination in comparison to the NS fresh (P<0.001), NS frozen treatments had the greatest PLM (P<0.05) and NS spermatozoa exhibited higher levels of superoxide anion production compared with SS spermatozoa (P<0.05). Experiment 1 found both fresh and frozen SS treatments had higher levels of viable acrosome-intact spermatozoa compared with the NS frozen treatments (P<0.01). PMID- 27372890 TI - The impact of chemical pollution on the resilience of soils under multiple stresses: A conceptual framework for future research. AB - Soils are faced with man-made chemical stress factors, such as the input of organic or metal-containing pesticides, in combination with non-chemical stressors like soil compaction and natural disturbance like drought. Although multiple stress factors are typically co-occurring in soil ecosystems, research in soil sciences on this aspect is limited and focuses mostly on single structural or functional endpoints. A mechanistic understanding of the reaction of soils to multiple stressors is currently lacking. Based on a review of resilience theory, we introduce a new concept for research on the ability of polluted soil (xenobiotics or other chemical pollutants as one stressor) to resist further natural or anthropogenic stress and to retain its functions and structure. There is strong indication that pollution as a primary stressor will change the system reaction of soil, i.e., its resilience, stability and resistance. It can be expected that pollution affects the physiological adaption of organisms and the functional redundancy of the soil to further stress. We hypothesize that the recovery of organisms and chemical-physical properties after impact of a follow-up stressor is faster in polluted soil than in non-polluted soil, i.e., polluted soil has a higher dynamical stability (dynamical stability=1/recovery time), whereas resilience of the contaminated soil is lower compared to that of not or less contaminated soil. Thus, a polluted soil might be more prone to change into another system regime after occurrence of further stress. We highlight this issue by compiling the literature exemplarily for the effects of Cu contamination and compaction on soil functions and structure. We propose to intensify research on effects of combined stresses involving a multidisciplinary team of experts and provide suggestions for corresponding experiments. Our concept offers thus a framework for system level analysis of soils paving the way to enhance ecological theory. PMID- 27372891 TI - Granulometric and magnetic properties of deposited particles in the Beijing subway and the implications for air quality management. AB - The subway system is an important traffic facility in Beijing and its internal air quality is an environmental issue that could potentially affect millions of people every day. Due to the intrinsic nature of rail abrasion in subway tunnels, iron-containing particles can be generated and become suspended in the subway environment. While some studies (e.g. Li et al., 2006) have monitored the in train levels of PM2.5 (particles<2.5MUm), there is a lack of systematic assessment of the concentration and characteristics of iron-containing particles in the Beijing subway system. Here we report results of a study on the granulometric and magnetic properties of deposited particle samples collected at different localities of the Beijing subway system. Our results show that the subway samples are characterized by the presence of fine particles. Volume proportions of 6.1+/-1.3% for particles<2.5MUm and 27.5+/-6.1% for particles<10MUm are found in the bulk subway samples. These samples exhibit a strong magnetic signal, which is approximately two orders of magnitude higher than that in naturally deposited particles collected in Beijing. Fine grained ferromagnetic and ferrimagnetic minerals (e.g. iron and magnetite, respectively) are identified from mineral magnetic measurements and scanning electric microscopy. The samples collected from the Beijing stations with platform screen doors are found to be magnetically stronger and finer than those without them, suggesting that platform screen doors have failed to block the fine iron containing particles released from the rail tunnel. Given the potential health consequences of fine suspended iron-containing particles, our results have important implications for air quality management in the Beijing subway system. PMID- 27372892 TI - The effect of a structured personalized ergonomic intervention program for hospital nurses with reported musculoskeletal pain: An assigned randomized control trial. AB - BACKGROUND: Intervention programs for hospital nurses with musculoskeletal pain present a challenge for the health professions. OBJECTIVE: To examine the effect of a structured personalized ergonomic intervention program for hospital nurses with musculoskeletal pain. METHODS: In a randomised controlled trial, 31 nurses from one central hospital with musculoskeletal pain were observed at work. A multi-stage study that included the Nordic Musculoskeletal Questionnaire, Karasek's questionnaire, The Rapid Entire Body Assessment, and an intervention program was completed with 14 nurses, while the remaining 17 were assigned to a control group. The intervention program was carried out by one physiotherapist and included four meetings over three months. The control group received only instruction sheets. Data on body posture and frequency and intensity of pain were collected before and at three months after the termination of the intervention program. RESULTS: Compared with the control group, the intervention group showed an improvement in REBA scores and in posture that is considered risk factor for work-related musculoskeletal discomfort disorders [p < 0.001], but there were no significant differences in the number of body parts in pain or in the level of musculoskeletal pain. CONCLUSIONS: The intervention was shown to be effective in reducing risk factors for work-related musculoskeletal disorders over a short follow-up period. A long-term study is required to determine if this effect is preserved over a longer period and to determine whether the intervention can reduce musculoskeletal symptoms. PMID- 27372893 TI - The effect of psychosocial stress on muscle activity during computer work: Comparative study between desktop computer and mobile computing products. AB - BACKGROUND: The popularity of mobile computing products is well known. Thus, it is crucial to evaluate their contribution to musculoskeletal disorders during computer usage under both comfortable and stressful environments. OBJECTIVE: This study explores the effect of different computer products' usages with different tasks used to induce psychosocial stress on muscle activity. METHODS: Fourteen male subjects performed computer tasks: sixteen combinations of four different computer products with four different tasks used to induce stress. Electromyography for four muscles on the forearm, shoulder and neck regions and task performances were recorded. RESULTS: The increment of trapezius muscle activity was dependent on the task used to induce the stress where a higher level of stress made a greater increment. However, this relationship was not found in the other three muscles. Besides that, compared to desktop and laptop use, the lowest activity for all muscles was obtained during the use of a tablet or smart phone. The best net performance was obtained in a comfortable environment. However, during stressful conditions, the best performance can be obtained using the device that a user is most comfortable with or has the most experience with. CONCLUSIONS: Different computer products and different levels of stress play a big role in muscle activity during computer work. Both of these factors must be taken into account in order to reduce the occurrence of musculoskeletal disorders or problems. PMID- 27372894 TI - Nutritional and food insecurity of construction workers. AB - BACKGROUND: Construction workers have intensive contact with their workplace and are possibly susceptible to Nutritional and Food Insecurity. OBJECTIVE: This paper assessed the Food Security status, diet and anthropometric measures of workers in the Construction Industry living in the city of Joao Pessoa, PB. METHODS: This cross-sectional study included 59 workers housed at construction sites. The workers were given the Brazilian Scale for Measuring Food Insecurity and Nutrition, had anthropometric measures taken and completed the Diet Quality Index, comparing their eating at the construction site and at home. Statistical analyses described the mean, standard deviation, frequency and Pearson correlations. RESULTS: Food Insecurity was reported by 71.2% of the workers, and 69.5% were overweight. The mean values of the Healthy Eating Index suggested that the workers' diets were in need of modification. There were statistically significant inverse associations among the Healthy Eating Index and Body Mass Index, waist circumference, percentage of total fat and cholesterol. CONCLUSIONS: Values obtained using the Scale showed Food Insecurity coupled with high excess weight and dietary inadequacies, revealing that these workers are at risk for health problems. PMID- 27372895 TI - Construction fatality due to electrical contact in Ontario, Canada, 1997-2007. AB - BACKGROUND: Electrical contact is a leading cause of occupational fatality in the construction industry. However, research on the factors that contribute to electricity-related fatality in construction is limited. OBJECTIVES: To characterize, using an adapted Haddon's Matrix, the factors that contribute to electricity-related occupational fatalities in the construction industry in Ontario, Canada. METHODS: Coroner's data on occupational electricity-related fatalities between 1997-2007 in the construction industry were acquired from the Ontario Ministry of Labour. Using an adapted Haddon's Matrix, we characterized worker, agent, and environmental characteristics of electricity-related occupational fatalities in the province through a narrative text analysis. RESULTS: Electrical contact was responsible for 15% of all occupational fatalities among construction workers in Ontario. Factors associated with said occupational fatalities included direct contact with electrical sources, lower voltage sources, and working outdoors. CONCLUSIONS: This study provides a profile of electricity-related occupational fatalities among construction workers in Ontario, and can be used to inform safety regulations. PMID- 27372896 TI - An interview guide for clinicians to identify a young disabled person's motivation to work. AB - BACKGROUND: The percentage of young people with disabilities who are employed is relatively low. Motivation is considered to be an important factor in facilitating or hindering their ability to obtain employment. OBJECTIVE: We aimed to develop a topic list that could serve as an interview guide for professionals in occupational health care which would aid them in their discussion of work motivation-related issues with this group. METHODS: We systematically searched Pubmed, PsychInfo and Picarta. Studies were included if they described aspects of work motivation and/or instruments that assess work motivation. Based on the results of our literature survey, we developed a list of topics that had been shown to be related to work motivation. RESULTS: Our search resulted in 12 articles describing aspects of work motivation and 17 articles describing instruments that assess work motivation. The aspects that we found were intrinsic motivation, extrinsic motivation, goal setting, self-efficacy, expectancy, values and work readiness. Based on this information we developed an interview guide that includes seven topic areas: intrinsic motivation, extrinsic motivation, goal setting, expectancy, values, self- efficacy, and work readiness. CONCLUSION: The topics within the interview guide and the literature survey data that is presented will shed light on the role that motivation plays on the work participation among young people with disabilities. PMID- 27372897 TI - The effects of gardening on quality of life in people with stroke. AB - BACKGROUND: Compared with traditional rehabilitation, gardening has been viewed as a more occupation-based intervention to help patients improve functional performance. However, there is still a need for evidence-based research into what factors interact to create the beneficial effects of gardening for people who have sustained a cerebral vascular accident (CVA). OBJECTIVE: To explore how plant, gender, and the time after stroke onset influenced improvements in the quality of life of patients in a gardening program. METHODS: One treatment of tending short-term plants, and another treatment of tending long-term plants were compared. Quality of life improvement was evaluated according to three factors: plant, gender, and the time after stroke onset. The data were analyzed with 2k replicated factorial designs. RESULTS: The 2k factorial design with replication indicated significant effects on both the social role and the family role. For the social role, the interaction of plant and gender difference was significant. For the family role, the significant effects were found on interaction of plant with both gender and the time after stroke onset. CONCLUSIONS: Tending plants with different life cycles has varied effects on the quality of life of people who have sustained a CVA. Factors related to gender and the time after stroke onset influenced role competency in this sample. PMID- 27372898 TI - Accompanying citizen of persons with traumatic brain injury in a community integration project: An exploration of the role. AB - BACKGROUND: The APIC (Citizen Accompaniment Project for Community Integration) is an innovative program that seeks to increase the community integration of people with a traumatic brain injury (TBI) by offering the support of an accompanying citizen (AC) in the accomplishment of significant life activities. OBJECTIVE: This article aims to better define the AC's role in this process, by underlining the mental health risks they face, the strategies they use, and the impacts the role has on their own lives. METHODS: This qualitative study is based on the analysis of interviews conducted with the AC following the first year of implementation. The data is part of a larger project aimed at the implementation and evaluation of APIC program. The data were analysed according to the rules of thematic content analysis, which encourages grouping main ideas into categories. This is an iterative process allowing for the constant emergence of new categories during the analysis. RESULTS: Accompaniment is full of joys and positive moments for the AC and participants. However, some difficult situations are encountered and the AC are constantly faced with challenges and constraints. The emerging study themes are as follows: the environment, the characteristics of the person accompanied, the AC's personal limits, and the ambiguities in the accompanier-accompanied relationship. CONCLUSIONS: Five principles drawn from the results will help oversee this practice more efficiently and limit the mental health risks of accompaniers. These findings may permit further development of this type of program for people living with disabilities. PMID- 27372899 TI - Role of heparin and non heparin binding serpins in coagulation and angiogenesis: A complex interplay. AB - Pro-coagulant, anti-coagulant and fibrinolytic pathways are responsible for maintaining hemostatic balance under physiological conditions. Any deviation from these pathways would result in hypercoagulability leading to life threatening diseases like myocardial infarction, stroke, portal vein thrombosis, deep vein thrombosis (DVT) and pulmonary embolism (PE). Angiogenesis is the process of sprouting of new blood vessels from pre-existing ones and plays a critical role in vascular repair, diabetic retinopathy, chronic inflammation and cancer progression. Serpins; a superfamily of protease inhibitors, play a key role in regulating both angiogenesis and coagulation. They are characterized by the presence of highly conserved secondary structure comprising of 3 beta-sheets and 7-9 alpha-helices. Inhibitory role of serpins is modulated by binding to cofactors, specially heparin and heparan sulfate proteoglycans (HSPGs) present on cell surfaces and extracellular matrix. Heparin and HSPGs are the mainstay of anti-coagulant therapy and also have therapeutic potential as anti-angiogenic inhibitors. Many of the heparin binding serpins that regulate coagulation cascade are also potent inhibitors of angiogenesis. Understanding the molecular mechanism of the switch between their specific anti-coagulant and anti-angiogenic role during inflammation, stress and regular hemostasis is important. In this review, we have tried to integrate the role of different serpins, their interaction with cofactors and their interplay in regulating coagulation and angiogenesis. PMID- 27372900 TI - Trifluoroethanol modulates alpha-synuclein amyloid-like aggregate formation, stability and dissolution. AB - The conversion of proteins into amyloid fibrils and other amyloid-like aggregates is closely connected to the onset of a series of age-related pathologies. Upon changes in environmental conditions, amyloid-like aggregates may also undergo disassembly into oligomeric aggregates, the latter being recognized as key effectors in toxicity. This indicates new possible routes for in vivo accumulation of toxic species. In the light of the recognized implication of alpha-Synuclein (alphaSN) in Parkinson's disease, we present an experimental study on supramolecular assembly of alphaSN with a focus on stability and disassembly paths of such supramolecular aggregate species. Using spectroscopic techniques, two-photon microscopy, small-angle X-ray scattering and atomic force microscopy, we report evidences on how the stability of alphaSN amyloid-like aggregates can be altered by changing solution conditions. We show that amyloid like aggregate formation can be induced at high temperature in the presence of trifluoroethanol (TFE). Moreover, sudden disassembly or further structural reorganisation toward higher hierarchical species can be induced by varying TFE concentration. Our results may contribute in deciphering fundamental mechanisms and interactions underlying supramolecular clustering/dissolution of alphaSN oligomers in cells. PMID- 27372901 TI - Preferential solvation of lysozyme in dimethyl sulfoxide/water binary mixture probed by terahertz spectroscopy. AB - We report the changes in the hydration dynamics around a model protein hen egg white lysozyme (HEWL) in water-dimethyl sulfoxide (DMSO) binary mixture using THz time domain spectroscopy (TTDS) technique. DMSO molecules get preferentially solvated at the protein surface, as indicated by circular dichroism (CD) and Fourier transform infrared (FTIR) study in the mid-infrared region, resulting in a conformational change in the protein, which consequently modifies the associated hydration dynamics. As a control we also study the collective hydration dynamics of water-DMSO binary mixture and it is found that it follows a non-ideal behavior owing to the formation of DMSO-water clusters. It is observed that the cooperative dynamics of water at the protein surface does follow the DMSO-mediated conformational modulation of the protein. PMID- 27372902 TI - Targeting alertness to improve cognition in older adults: A preliminary report of benefits in executive function and skill acquisition. AB - Efficient self-regulation of alertness declines with age exacerbating normal declines in performance across multiple cognitive domains, including learning and skill acquisition. Previous cognitive intervention studies have shown that it is possible to enhance alertness in patients with acquired brain injury and marked attention impairments, and that this benefit generalizes to improvements in more global cognitive functions. In the current preliminary studies, we sought to test whether this approach, that targets both tonic (over a period of minutes) and phasic (moment-to-moment) alertness, can improve key executive functioning declines in older adults, and enhance the rate of skill acquisition. The results of both Experiments 1 and 2 demonstrate that, compared to active control (AC) training, alertness training significantly enhanced performance in several validated executive function measures. In Experiment 2, alertness training significantly improved skill acquisition compared to AC training in a well characterized speed of processing (SOP) task, with the largest benefits shown in the most challenging SOP blocks. The results of the current study suggest that targeting intrinsic alertness through cognitive training provides a novel approach to improve executive functions in older adults and may be a useful adjunct treatment to enhance benefits gained in other clinically validated treatments. PMID- 27372903 TI - A systematic review of the effect of telephone, internet or combined support for carers of people living with Alzheimer's, vascular or mixed dementia in the community. AB - BACKGROUND: The objective of this review was to assess the effectiveness of interventions delivered by telephone, internet or combined formats to support carers of community dwelling people living with Alzheimer's Disease, vascular dementia or mixed dementia. METHOD: English language literature published up to 2016 was searched. The initial search included: MEDLINE, Cumulative Index to Nursing and Allied Health (CINAHL), and PsycINFO. A second search was conducted using Medical Subject Headings (MeSH) and keywords for eight databases. The review included randomised controlled trials, non-randomised controlled trials, quasi-experimental and pre-post studies from published and grey literature. Studies selected for retrieval were assessed by three independent reviewers for methodological validity prior to inclusion in the review using standardised critical appraisal instruments. RESULTS: Twenty-two studies were included in the review of which 13 were studies of telephone-delivered interventions, five were internet-delivered interventions and four were delivered in a combination of telephone and internet formats. In this review the successful outcomes from the combined telephone and internet delivery exceeded that of telephone alone and internet alone. Very few studies addressed programs for specific types of dementia. CONCLUSION: When considering the ratio of number of studies to successful outcomes, combined telephone and internet delivery of multicomponent interventions demonstrated relatively more positive outcomes in reducing depression, burden and increasing self-efficacy than telephone alone or internet alone. Further studies are necessary to evaluate the effectiveness of interventions targeted at specific types of dementia and to understand which components of interventions are most effective. PMID- 27372904 TI - Visinin-Like Protein-3 Modulates the Interaction Between Cytochrome b 5 and NADH Cytochrome b 5 Reductase in a Ca2+-Dependent Manner. AB - Visinin-like proteins (VILIPs) belong to the calcium sensor protein family. VILIP 1 has been examined as a cerebrospinal fluid biomarker and as a potential indicator for cognitive decline in Alzheimer's disease (AD). However, little is known about VILIP-3 protein biochemistry. We performed co-immunoprecipitation experiments to examine whether VILIP-3 can interact with reduced nicotine adenine dinucleotide (NADH)-cytochrome b 5 reductase. We also evaluated the specificity of cytochrome b 5 within the visinin-like protein subfamily and identified cytochrome P450 isoforms in the brain. In this study, we show that cytochrome b 5 has an affinity for hippocalcin, neurocalcin-delta, and VILIP-3, but not visinin like protein-1. VILIP-3 was also shown to interact with NADH-cytochrome b 5 reductase in a Ca2+-dependent manner. These results suggest that VILIP-3, hippocalcin, and neurocalcin-delta provide a Ca2+-dependent modulation to the NADH-dependent microsomal electron transport. The results also suggest that future therapeutic strategies that target calcium-signaling pathways and VILIPs may be of value. PMID- 27372905 TI - Identifying potential environmental impacts of waste handling strategies in textile industry. AB - Waste management is a successful instrument to minimize generated waste and improve environmental conditions. In spite of the large share of developing countries in the textile industry, limited information is available concerning the waste management strategies implemented for textiles on those countries and their environmental impacts. In the current study, two waste management approaches for hazardous solid waste treatment of acrylic fibers (landfill and incineration) were investigated. The main research questions were: What are the different impacts of each waste management strategy? Which waste management strategy is more ecofriendly? Life cycle assessment was employed in order to model the environmental impacts of each waste streaming approach separately then compare them together. Results revealed that incineration was the more ecofriendly approach. Highest impacts of both approaches were on ecotoxicity and carcinogenic potentials due to release of metals from pigment wastes. Landfill had an impact of 46.8 % on human health as compared to 28 % by incineration. Incineration impact on ecosystem quality was higher than landfill impact (68.4 and 51.3 %, respectively). As for resources category, incineration had a higher impact than landfill (3.5 and 2.0 %, respectively). Those impacts could be mitigated if state-of-the-art landfill or incinerator were used and could be reduced by applying waste to energy approaches for both management systems In conclusion, shifting waste treatment from landfill to incineration would decrease the overall environmental impacts and allow energy recovery. The potential of waste to energy approach by incineration with heat recovery could be considered in further studies. Future research is needed in order to assess the implementation of waste management systems and the preferable waste management strategies in the textile industry on developing countries. PMID- 27372906 TI - Spinal Koebner phenomenon: Medullar sarcoidosis facing a discal hernia. PMID- 27372907 TI - Cardiovascular disease risk in young Indigenous Australians: a snapshot of current preventive health care. AB - OBJECTIVE: To examine preventive health attendance and recording of type 2 diabetes and cardiovascular disease risk factors and their management in young Aboriginal peoples and Torres Strait Islanders (Indigenous Australians) at primary health care centres (PHCs). METHODS: This descriptive cross-sectional study audited medical records of 1,986 Indigenous people aged 15-34 years attending 93 Australian PHCs. Measurements included blood pressure (BP), blood glucose level (BGL), smoking status, body mass index (BMI) and lipid profile. RESULTS: Last attendance was most commonly for acute care (46%); 12% attended for preventive assessment. BP was recorded in 85% (1,686/1,986), BGL 63% (1,244/1,986), smoking status 52% (1,033/1,986), BMI 37% (743/1,986) and lipids 31% (625/1,986). Of those with a recorded assessment, elevated BGL (39%, 479/1,244), smoking (63%, 649/1,033), overweight/obesity (51%, 381/743) and dyslipidaemia (73%, 458/625) were common. Follow-up of abnormal results was documented for elevated BP 28% (34/120), elevated BGL 17% (79/479), smoking 65% (421/649), overweight/obesity 11% (40/381) and abnormal lipids 16% (75/458). CONCLUSIONS: These findings highlight the importance of raising awareness and assessment of chronic disease risk factors in young Indigenous people and implementing preventive health care strategies. IMPLICATIONS: Strengthening the capacity of PHCs to provide preventive health care may contribute to reducing the chronic disease burden experienced by young Indigenous people. PMID- 27372908 TI - Association of concurrent acid-suppression therapy with survival outcomes and adverse event incidence in oncology patients receiving erlotinib. AB - PURPOSE: Acid-suppression therapy is known to decrease the systemic exposure of erlotinib. The erlotinib prescribing information recommends staggering dosing with a histamine-2 receptor antagonist (H2RA) and avoiding concurrent use of a proton pump inhibitor (PPI). This retrospective analysis evaluated the frequency of concurrent acid-suppression therapy in oncology patients receiving erlotinib and its association with outcomes. METHODS: All patients prescribed erlotinib within UC San Diego Health System between February 26, 2011, and February 28, 2014, were assessed for eligibility, survival outcomes and adverse events. RESULTS: Of the 76 patients in the analysis, 24 were prescribed both a PPI and an H2RA with erlotinib therapy (31.6 %). The two patient groups, with (n = 24) and without PPI/H2RA (n = 52), were similar in clinical characteristics and erlotinib dose. One patient received an H2RA therapy alone and was excluded from the analysis; no one received PPI therapy alone. Patients receiving erlotinib alone had a longer median progression-free survival (PFS) compared to patients with concurrent PPI/H2RA therapy (11.0 months vs. 5.3 months; P = 0.029). Overall survival (OS) and incidence of rash and/or diarrhea did not correlate with use of acid-suppression therapy. CONCLUSION: Nearly one-third of patients received acid suppression therapy. Patients treated with erlotinib and PPI/H2RA therapy had shorter PFS, but similar OS and adverse event profile compared to those who did not receive acid-suppression. PMID- 27372909 TI - Evaluation of Macular Ganglion Cell Complex and Peripapillary Retinal Nerve Fiber Layer in Primary Craniopharyngioma by Fourier-Domain Optical Coherence Tomography. AB - BACKGROUND The aim of this study was to compare the differences in macular ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (pRNFL) in child and adult patients with primary craniopharyngioma by Fourier-domain optical coherence tomography (FD-OCT) and to evaluate their significance in the diagnosis of primary craniopharyngioma. MATERIAL AND METHODS Ninety-six participants were divided into 3 groups: 32 in the child craniopharyngioma group (CCG) and 32 in the adult craniopharyngioma group (ACG) who were treated in Beijing Tiantan Hospital between November 2013 and October 2014, and 32 in the normal group (NG). All subjects were scanned by FD-OCT to map GCC and pRNFL thicknesses. Spearman correlation coefficient was used to assess the correlation between GCC and pRNFL thickness, and pRNFL thickness and optic nerve head (ONH) parameters, including horizontal cup-disc ratio (HCDR), vertical cup-disc ratio (VCDR), optic disc area (ODA), and cup area (CA), respectively. RESULTS The correlation between GCC and pRNFL thickness in the CCG was slightly stronger compared with the ACG. A significant difference in GCC thickness was observed among the CCG, ACG, and NG. Although the pRNFL thickness in both the CCG and ACG was significantly higher than that in NG, no significant difference in pRNFL thickness was detected between the 2 craniopharyngioma groups. The average, superior, and inferior pRNFL thicknesses were negatively correlated with VCDR in the CCG (in double eyes) and ACG (only in left eyes). CONCLUSIONS GCC was more sensitive than pRNFL in detecting optic nerve damage in the eyes of craniopharyngioma patients. A thinner pRNFL was especially correlated with VCDR in child craniopharyngioma patients. PMID- 27372910 TI - Erratum to: Transvaginal hybrid NOTES cholecystectomy-results of a randomized clinical trial after 6 months. PMID- 27372911 TI - Canine cutaneous mast cell tumors: A combined clinical and pathologic approach to diagnosis, prognosis, and treatment selection. AB - In view of the varied biologic behavior and the costs of treatment for canine cutaneous mast cell tumors, development of appropriate treatment plans for individual affected dogs can be difficult, but decisions regarding treatment should be made using a systematic, evidence-based approach. This manuscript reviews the current state of diagnostics and prognostication of canine cutaneous mast cell tumors, and suggests a combined approach based on clinical and pathologic assessment for decision making regarding treatment choices. The current state of histologic grading, evaluation of proliferation indices, evaluation of mutations in the c-kit gene and KIT expression, evaluation of excision and clinical staging are examined. On the basis of the current understanding of prognostication and treatment response, algorithms for selection of local and systemic therapy are presented. PMID- 27372912 TI - Nanosilica-based molecularly imprinted polymer nanoshell for specific recognition and determination of rhodamine B in red wine and beverages. AB - A new and facile rhodamine B (RhB)-imprinted polymer nanoshell coating for SiO2 nanoparticles was readily prepared by a combination of silica gel modification and molecular surface imprinting. The RhB-imprinted polymers (RhB-MIPs) were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and UV-vis spectroscopy; the binding properties and selectivity of these MIPs were investigated in detail. The uniformly imprinted nanoparticles displayed a rather thin shell thickness (23nm) with highly effective recognition sites, showing homogenous distribution and monolayer adsorption. The maximum MIP adsorption capacity (Qm) was as high as 45.2mgg(-1), with an adsorption equilibrium time of about 15min at ambient temperature. Dynamic rebinding experiments showed that chemical adsorption is crucial for RhB binding to RhB MIPs. The adsorption isotherm for RhB-MIPs binding could also be described by the Langmuir equation at different temperatures and pH values. Increasing temperature led to an enhanced Qm, a decreased dissociation constant (K'd), and a more negative free energy (DeltaG), indicating that adsorption is favored at higher temperatures. Moreover, the adsorption capacity of RhB was remarkably affected by pH. At pH>7, the adsorption of RhB was driven by hydrogen bonding interactions, while at pH<7 electrostatic forces were dominant. Additionally, the MIPs also showed specific recognition of RhB from the standard mixture solution containing five structurally analogs. This method was also successfully employed to determine RhB content in red wine and beverages using three levels of spiking, with recoveries in the range of 91.6-93.1% and relative standard deviations lower than 4.1%. PMID- 27372913 TI - Facial synthesis of nickel(II)-immobilized carboxyl cotton chelator for purification of histidine-tagged proteins. AB - Immobilized metal affinity chromatography (IMAC) technique is frequently used in the purification of histidine-tagged (His-tagged) recombinant proteins. In this study, nickel(II)-immobilized carboxyl cotton chelator (CCC-Ni2+) fibers was synthesized by a simple method based on the coordination effect between Ni2+ and carboxyl group. The nickel content of the CCC-Ni2+ fibers was determined to be 5 times larger than that of Ni2+-immobilized sulfhydryl cotton fiber (SCF-Ni2+) fibers developed in our previous work. The prepared CCC-Ni2+ fibers were then applied for the selective and rapid separation of His-tagged protein from escherichia coli (E. coli) cell lysates on the basis of the high affinity of Ni2+ to 6*His with a lab-in-syringe format. Benefiting from the good biological compatibility and high nickel content, the results showed that CCC-Ni2+ fibers were able to selectively capture His-tagged proteins from complex E. coli cell lysates and exhibited a relatively large adsorption capacity toward His-tagged protein. The recoveries of His-tagged GFP in E. coli cell lysates were in the range of 89.8%-106.7% with the relative standard deviations (RSDs) less than 9.4% (intra-day) and 10.3% (inter-day). Taken together, this efficient approach for the purification of recombinant proteins extends the application of CCC-based fibrous materials in biological analysis. PMID- 27372914 TI - A proliferation inducing ligand (APRIL) promotes IL-10 production and regulatory functions of human B cells. AB - B cells may have a negative regulatory role, mainly mediated by interleukin 10 (IL-10). We recently showed that regulatory B-cell functions are impaired in patients with rheumatoid arthritis (RA) and that mice transgenic for a proliferation-inducing ligand (APRIL) are protected against collagen-induced arthritis. We aimed to explore the effect of APRIL on human B-cell IL-10 production, in healthy subjects and in patients with RA. The IL-10 production of B-cell was greater with APRIL than with BLyS or control medium, in a dose dependent manner. TACI expression was greater in IL-10 producing B cells (B10) than non-IL-10-producing B cells whereas BAFF-R expression was lower. TNF-alpha and IFN-gamma secretion of T-cells were decreased by APRIL-stimulated B cells. APRIL stimulated STAT3 and STAT3 inhibition decreased B10 cells. APRIL also promoted B10 cells in RA patients. In conclusion, APRIL but not BLyS promotes IL 10 production by CpG-activated B cells and enhances the regulatory role of B cells on T cells. B10 cells in RA patients are responsive to APRIL, which suggests a possible therapeutic application of APRIL to expand B10 cells. This could also explain the difference of clinical efficacy observed between belimumab and atacicept in RA. PMID- 27372915 TI - Annexin A2, autoimmunity, anxiety and depression. AB - OBJECTIVES: Antiphospholipid syndrome (APS) is associated with neurological manifestations and one of the novel autoantigens associated with this disease is Annexin A2 (ANXA2). In this work we have examined the effect of high levels of autoantibodies to ANXA2 on the brain in a mouse model. METHODS: Recombinant ANXA2 emulsified in adjuvant was used to immunize mice while mice immunized with adjuvant only served as controls. At peak antibody levels the animal underwent behavioral and cognitive tests and their brains were examined for ANXA2 immunoglobulin G (IgG) and expression of ANXA2 and the closely linked protein p11. RESULTS: Very high levels of anti-ANXA2 antibodies (Abs) were associated with reduced anxiety in the open field 13.14% +/- 0.89% of the time in the center compared to 8.64% +/- 0.91% observed in the control mice (p < 0.001 by t-test). A forced swim test found significantly less depression manifested by immobility in the ANXA2 group. The changes in behavior were accompanied by a significant reduction in serum corticosteroid levels of ANXA2 group compared to controls. Moreover, higher levels of total IgG and p11 expression were found in ANXA2 group brains. Lower levels of circulating anti-ANXA2 Abs were not associated with behavioral changes. CONCLUSIONS: We have established an animal model with high levels of anti-ANXA2 Abs which induced IgG accumulation in the brain and specific anxiolytic and anti-depressive effects. This model promises to further our understanding of autoimmune disease such as APS and to provide better understanding of the role of the ANXA2-p11 complex in the brain. PMID- 27372916 TI - Ingested (oral) rituximab inhibits EAE. AB - BACKGROUND: Blocking CD20 can inhibit autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA). OBJECTIVE: We examined whether an antibody against CD20, rituximab (RTX) (Rituxan(r)), used clinically in oncology, MS and RA would have similar anti-inflammatory effects in EAE after oral administration. DESIGN/METHODS: B6 mice were immunized with MOG peptide 35-55 and gavaged with control saline or RTX during ongoing disease. Splenocytes or CD4(+) T cells from control fed or RTX fed mice were adoptively transferred into active MOG peptide 35-55 immunized recipient mice during ongoing disease. Actively fed and recipient mice were examined for disease inhibition, inflammation, and cytokine responses. RESULTS: Ingested (oral) RTX inhibited ongoing disease and decreased inflammation. Adoptively transferred cells from RTX fed donors protected against actively induced disease and decreased inflammation. There was a decrease in Th1-like cytokines IFN-gamma and IL-12, IL-17 and TNF-alpha in active fed and adoptively treated recipients without upregulation of counter regulatory cytokines. CONCLUSIONS: Ingested (orally administered) RTX can inhibit disease, CNS inflammation, decrease pro-inflammatory IL-17 and Th1-like cytokines without increases in Th2-like anti-inflammatory cytokines. PMID- 27372917 TI - Tumor necrosis factor alpha neutralization has no direct effect on parasite burden, but causes impaired IFN-gamma production by spleen cells from human visceral leishmaniasis patients. AB - The pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha has an important role in control of experimental Leishmania donovani infection. Less is known about the role of TNF-alpha in human visceral leishmaniasis (VL). Evidence for a protective role is primarily based on case reports of VL development in individuals treated with TNF-alpha neutralizing antibody. In this study, we have evaluated how TNF-alpha neutralization affects parasite replication and cytokine production in ex vivo splenic aspirates (SA) from active VL patients. The effect of TNF-alpha neutralization on cell mediated antigen specific responses were also evaluated using whole blood cultures. Neutralization of TNF-alpha did not affect parasite numbers in SA cultures. Interferon (IFN)-gamma levels were significantly reduced, but interleukin (IL)-10 levels were unchanged in these cultures. Leishmania antigen stimulated SA produced significant TNF-alpha which suggests that TNF-alpha is actively produced in VL spleen. Further it stimulates IFN-gamma production, but no direct effect on parasite replication. PMID- 27372918 TI - Importance of fluorine in 2,3-dihydroquinazolinone and its interaction study with lysozyme. AB - The main aim of this study is to investigate the interaction of 7-fluoro-2,2 dimethyl-2,3-dihydroquinazolin-4(1H)-one with lysozyme through various spectrophotometric studies. The graph such as Stern-Volmer plot, modified Stern Volmer plot, double logarithmic plot and Van't Hoff plot were plotted to determine the various parameters essential for predicting the interaction. The interaction of the ligand with the protein was further confirmed by circular dichroism and NMR study. The molecular docking was performed and the results obtained were correlated with the other studies. The importance of fluorine was justified through the prediction of pKa values and the possible metabolic pathway using the in silico tools. In addition, the cytotoxicity of the compound was carried out using HeLa cancer cell. PMID- 27372919 TI - Fetal sex determination using NIPT and ultrasound as a method for diagnosing important fetal sex abnormalities. PMID- 27372920 TI - (1)H, (15)N, and (13)C resonance assignments of Staphylococcus aureus extracellular adherence protein domain 4. AB - The pathogenic bacterium Staphylococcus aureus has evolved to actively evade many aspects of the human innate immune system by expressing a series of secreted inhibitory proteins. Among these, the extracellular adherence protein (Eap) has been shown to inhibit the classical and lectin pathways of the complement system. By binding to complement component C4b, Eap is able to inhibit formation of the CP/LP C3 pro-convertase. Secreted full-length, mature Eap consists of four ~98 residue domains, all of which adopt a similar beta-grasp fold, and are connected through a short linker region. Through multiple biochemical approaches, it has been determined that the third and fourth domains of Eap are responsible for C4b binding. Here we report the backbone and side-chain resonance assignments of the 11.3 kDa fourth domain of Eap. The assignment data has been deposited in the BMRB database under the accession number 26726. PMID- 27372921 TI - Recombinant chicken interferon-alpha inhibits the replication of exogenous avian leukosis virus (ALV) in DF-1 cells. AB - Chickeninterferon alpha (ChIFNalpha) belongs to type I IFNs that are important antiviral cytokines. We investigated whether ChIFNalpha plays a role in avian leukosis virus (ALV) infections of chickens. Firstly, we explored the immune response to ALV in vivo by measuring cytokine expression profiles in the spleens and bursas of chickens during the late stages of ALV-J infection. The results indicated that ALV-J infection could induce a mixed Th1/Th2 cytokine response by elevating levels of both interleukin-2 (IL-2) and IL-10. In contrast, tumor necrosis factor alpha (TNF-alpha) levels decreased in the spleen while interferon beta (IFNbeta) and Toll-like receptor 7 (TLR7) expression levels in the bursa increased significantly. This indicated that ALV-J stimulates a Type I IFN response. Next, we found that different ALV subgroups or strains up-regulated chicken IFN regulatory factor 3 (ChIRF-3) promoter activity, suggesting that ALV infection could trigger Type I IFNs pathway in vitro. Accordingly, we further investigated ChIFNalpha antiviral effects on ALV replication in DF-1 cells by successfully expressing recombinant ChIFNalpha in Escherichia coli (E. coli) strain BL21. The specific activity of the purified rChIFNalpha protein was determined to be 4*10(7)U/mL. When added at 4000U/mL, the recombinant protein restrained ALV replication as measured by decreases in viral protein p27 levels and mRNA expression. This new reagent may be useful for prophylactic and therapeutic drug design. PMID- 27372922 TI - The alteration of pharmacokinetics of erlotinib and OSI420 in type 1 diabetic rabbits. AB - BACKGROUND: Alterations in blood glucose levels observed in diabetes, may change the pharmacokinetics of co-administered drugs and in consequence, the efficacy and safety of therapy. Many oncological patients are diabetics and it is important to determine the interaction of anticancer drugs with this chronic disease. Erlotinib is a tyrosine kinase inhibitor (TKI), approved for the treatment of patients with non-small-cell lung cancer and pancreatic cancer in combination with gemcitabine. The aim of the study was to investigate the influence of the diabetes on the pharmacokinetics of erlotinib in rabbits. Additionally, the effect of erlotinib on glucose levels was examined. METHODS: The pharmacokinetics of erlotinib was studied in healthy rabbits (n=6, control group) and type 1 diabetic rabbits (n=6, diabetic group). Erlotinib was administered in a single oral dose of 25mg. Plasma concentrations of erlotinib and its metabolite (OSI420) were measured with the validated method. RESULTS: The plasma concentrations of erlotinib and OSI420 were markedly increased in diabetic rabbits. Statistically significant differences between the groups were revealed for almost all analysed pharmacokinetic parameters for erlotinib and OSI420. The maximum glycaemia drop of 7.7-33.5% was observed in the diabetic animals, but no significant changes in glucose concentration were observed in the control group. CONCLUSIONS: The research proved the significant influence of diabetes on the pharmacokinetics of erlotinib and OSI420. Due to higher exposure to erlotinib, there may be an increased risk of adverse drug reactions in diabetic patients. Therefore, in some cases lower doses of the drug should be considered. PMID- 27372923 TI - Transforming growth factor beta-related genes in human retinal pigment epithelial cells after tacrolimus treatment. AB - BACKGROUND: The transforming growth factor beta (TGFbeta) family plays an important role in the pathogenesis of many diseases, including fibrotic pathologies of the eyes. The difficulties of surgical procedures contribute to the search for new treatment strategies for proliferative vitreoretinopathy. Therefore, the aim of this study was to investigate the expression profile of TGFbeta isoforms, their receptors, and TGFbeta-related genes in human retinal pigment epithelial cells (RPE) after tacrolimus (FK-506) treatment in the presence or absence of lipopolysaccharide (LPS)-induced inflammation. METHODS: The expression profile was analyzed using oligonucleotide microarrays and quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) techniques. RESULTS: Analysis using oligonucleotide microarrays revealed 20 statistically significant differentially expressed TGFbeta-related genes after LPS treatment in relation to control cells, and after tacrolimus and LPS treatment in relation to LPS-treated cells. Moreover, our results showed that mRNA levels for TGFbeta2 and TGFbetaR3 after tacrolimus treatment, and for TGFbetaR3 after tacrolimus and LPS treatment in RPE cells were decreased. In turn, in the presence of LPS-induced inflammation, TGFbeta2 mRNA level was increased. CONCLUSIONS: These results can be important in regard to the treatment of proliferative vitreoretinopathy, pathogenesis of which is associated with processes regulated by TGFbeta, such as inflammation, proliferation, epithelial mesenchymal transition (EMT), and fibrosis. PMID- 27372924 TI - Hydrogen sulfide down-regulates BACE1 and PS1 via activating PI3K/Akt pathway in the brain of APP/PS1 transgenic mouse. AB - BACKGROUND: Endogenous hydrogen sulfide (H2S) may have multiple physiological functions in brain. Our previous study showed that H2S improved spatial memory impairment and decreased the production of Abeta in APP/PS1 transgenic mice. However, many of the underlying mechanisms are not still being elucidated. The aim of the present study is to investigate the neuroprotective mechanisms of H2S involving in the activity of beta-secretase (BACE1), gamma-secretase (PS1) and alpha-secretase (ADAM17). METHODS: Morris water maze was used to measure the behavior change. The levels of Abeta40 and Abeta42 were quantified using colorimetric ELISA kits and immunohistochemical analysis. The levels of BACE1, PS1, ADAM17, pAkt, pp38MAPK, pERK and pJNK were tested by Western blot analysis in normal mice, APP/PS1 transgenic mice and 50MUmol/kg-NaHS-treated transgenic mice. On the basis of exogenous H2S treatment, LY294002 (inhibitors of PI3K/Akt) or PD98059 (inhibitors of MAPK/ERK) was injected into lateral cerebral ventricle. RESULTS: The levels of BACE1, PS1 and pp38MAPK were increased and ADAM17 were decreased in the APP/PS1 transgenic mice. After intraperitoneal administration of an H2S donor (NaHS) into APP/PS1 mice, the levels of BACE1, PS1 and pp38MAPK were reduced and ADAM17 increased. The level of pp38 MAPKs, pAkt and pERK1/2 was increased in APP/PS1 transgenic mice compared with normal mice (p<0.05). There was no difference in the expression of pJNK between AD transgenic mice and normal mice (p>0.05). These results demonstrated that LY294002 inhibited the effect of H2S on decreasing the BACE1 and PS1, reducing the level of Abeta and improving memory impairment in APP/PS1 transgenic mice. PD98059 had no influence on the expression of BACE1 and PS1. CONCLUSIONS: H2S inhibits the expression of BACE1 and PS1 by activating PI3K/Akt pathway in AD. PMID- 27372925 TI - [Not Available]. PMID- 27372927 TI - [Not Available]. PMID- 27372926 TI - Potential causative agents of acute gastroenteritis in households with preschool children: prevalence, risk factors, clinical relevance and household transmission. AB - Acute gastroenteritis (AGE) morbidity remains high amongst preschool children, posing a significant societal burden. Empirical data on AGE-causing agents is needed to gauge their clinical relevance and identify agent-specific targets for control. We assessed the prevalence, risk factors and association with symptoms for enteropathogens in households with preschool children. A monthly-repeated cross-sectional survey of enteropathogens in households with preschool children was performed. A parent-child pair per household (n = 907 households) provided faecal samples and reported their symptoms and potential risk exposures. Samples were tested by multiplex reverse transcription polymerase chain reaction (RT-PCR) for 19 enteropathogens. Associations were assessed using logistic regression. 28.3 % of children (n = 981) and 15.6 % of parents (n = 971) carried pathogenic bacteria and/or Escherichia coli-associated pathogenicity genes, and 6.5 % and 3.3 % carried viruses, respectively. Giardia lamblia (4.6 % of children, 2.5 % of parents) and Dientamoeba fragilis (36 %, 39 %, respectively) were the main parasites, and were associated with pet exposure. Living in rural areas was associated with carriage of pathogenic E. coli, norovirus I and D. fragilis. Pathogenic E. coli was associated with summertime and livestock exposure. Attending day-care centres increased the risk of carrying norovirus, sapovirus and G. lamblia. Viruses occurred mainly in winter and were associated with AGE symptoms. Child-parent associations were found for bacterial pathogenicity genes, viruses, G. lamblia and D. fragilis. Enteropathogens spread widely in households with preschool children, particularly viruses, which more often cause symptoms. While bacteria predominate during summer and in those exposed to livestock, viruses predominate in wintertime and, like G. lamblia, are widespread amongst day-care centre attendees. PMID- 27372928 TI - [Not Available]. PMID- 27372929 TI - [Not Available]. PMID- 27372930 TI - [Not Available]. PMID- 27372931 TI - [Not Available]. PMID- 27372932 TI - [Not Available]. PMID- 27372933 TI - [Not Available]. PMID- 27372935 TI - [Not Available]. PMID- 27372934 TI - [Not Available]. PMID- 27372936 TI - [Not Available]. PMID- 27372937 TI - [Not Available]. PMID- 27372938 TI - [Not Available]. PMID- 27372939 TI - [Not Available]. PMID- 27372940 TI - [Not Available]. PMID- 27372941 TI - [Not Available]. PMID- 27372942 TI - [Not Available]. PMID- 27372944 TI - A minimally invasive micro sampler for quantitative sampling with an ultrahigh aspect-ratio microneedle and a PDMS actuator. AB - This study describes a novel micro sampler consisting of an ultrahigh-aspect ratio microneedle and a PDMS actuator. The microneedle was fabricated by a new method which introduced reshaped photoresist technology to form a flow channel inside. The microneedle includes two parts: shaft and pedestal. In this study, the shaft length is 1500 MUm with a 45 degrees taper angle on the tip and pedestal is 1000 MUm. Besides, the shaft and pedestal are connected by an arc connection structure with a length of 600 MUm. The microneedles have sufficient mechanical strength to insert into skin with a wide safety margin which was proved by mechanics tests. Moreover, a PDMS actuator with a chamber inside was designed and fabricated in this study. The chamber, acting as a reservoir in sampling process as well as providing power, was optimized by finite element analysis (FEA) to decrease dead volume and improve sampling precision. The micro sampler just needs finger press to activate the sampling process as well as used for quantitative micro injection to some extent. And a volume of 31.5 +/- 0.8 MUl blood was successfully sampled from the ear artery of a rabbit. This micro sampler is suitable for micro sampling for diagnose or therapy in biomedical field. PMID- 27372943 TI - Abnormalities in the Metabolism of Fatty Acids and Triacylglycerols in the Liver of the Goto-Kakizaki Rat: A Model for Non-Obese Type 2 Diabetes. AB - The Goto-Kakizaki (GK) rat is widely used as an animal model for spontaneous onset type 2 diabetes without obesity; nevertheless, little information is available on the metabolism of fatty acids and triacylglycerols (TAG) in their livers. We investigated the mechanisms underlying the alterations in the metabolism of fatty acids and TAG in their livers, in comparison with Zucker (fa/fa) rats, which are obese and insulin resistant. Lipid profiles, the expression of genes for enzymes and proteins related to the metabolism of fatty acid and TAG, de novo synthesis of fatty acids and TAG in vivo, fatty acid synthase activity in vitro, fatty acid oxidation in liver slices, and very-low density-lipoprotein (VLDL)-TAG secretion in vivo were estimated. Our results revealed that (1) the TAG accumulation was moderate, (2) the de novo fatty acid synthesis was increased by upregulation of fatty acid synthase in a post transcriptional manner, (3) fatty acid oxidation was also augmented through the induction of carnitine palmitoyltransferase 1a, and (4) the secretion rate of VLDL-TAG remained unchanged in the livers of GK rats. These results suggest that, despite the fact that GK rats exhibit non-obese type 2 diabetes, the upregulation of de novo lipogenesis is largely compensated by the upregulation of fatty acid oxidation, resulting in only moderate increase in TAG accumulation in the liver. PMID- 27372945 TI - Universal disease-specific outcome instruments for spine trauma: a global perspective on relevant parameters to evaluate clinical and functional outcomes of thoracic and lumbar spine trauma patients. AB - PURPOSE: Besides a patient reported outcome measure, the AOSpine Knowledge Forum Trauma aims to develop a new concept of a surgeon reported outcome measure (SROM) for spine trauma patients. This study aims to identify parameters that spine surgeons consider relevant to evaluate clinical and functional outcomes of thoracic and lumbar spine trauma patients. METHODS: An international cross sectional web-based survey was conducted among spine surgeons from the five AOSpine International world regions. They were asked to evaluate the relevance of a compilation of 16 clinical and radiological parameters for thoracic and lumbar spine trauma patients, both for the short term (3 months-2 years) and long term (>=2 years), on a five-point scale. The responses were analyzed using descriptive statistics, frequency analysis, and Kruskal-Wallis test. RESULTS: Out of the 279 invited members of AOSpine International and the International Spinal Cord Society, 118 (42.3 %) participated in this study. Of the 16 surveyed parameters, 5 were identified as relevant by at least 70 % of the participants. Neurological status was identified as most relevant. In contrast, five parameters were not deemed relevant for any spine region or time period, except for comorbidity. Only minor differences were observed when analyzing the responses according to each world region, spine surgeons' clinical experience, or professional background. CONCLUSIONS: Including a large and representative sample of spine trauma experts, this study identified parameters to evaluate clinical and functional outcomes of thoracic and lumbar spine trauma patients. The results form the basis for the development of a SROM for this specific patient population. PMID- 27372946 TI - Characterization of the median sacral artery course at the sacral promontory using contrast-enhanced computed tomography. AB - INTRODUCTION AND HYPOTHESIS: Laparoscopic sacral colpopexy (SC) is increasingly utilized in the surgical management of apical prolapse. It involves attachment of a synthetic mesh to the sacral promontory and to the prolapsed vaginal walls. The median sacral artery (MSA) runs close to the site of mesh attachment and is therefore prone to intraoperative injury, which may lead to profound hemorrhaging. The aim of this study was to determine the location of the MSA at the level of the sacral promontory with regard to adjacent visible anatomical landmarks. Surgeons may use this information to reduce the risk for presacral bleeding. METHODS: Sixty consecutive contrast-enhanced pelvic computed tomography scans were revised, and the location of the MSA at the level of the sacral promontory was determined in relation to the ureters, iliac arteries, sacral midline, and aortic bifurcation. RESULTS: The MSA runs 0.2 +/- 3.9 mm left to the midline of the sacral promontory and 48.0 +/- 15.4 mm caudal to the aortic bifurcation. The ureters, internal and external iliac arteries on the right were significantly closer to the MSA than on the left (30.0 +/- 7.1 vs 35.2 +/- 8.8 mm, p = 0.001; 21.5 +/- 6.8 vs 30.3 +/- 8.4 mm, p < 0.0001; 32.8 +/- 10.2 vs 41.9 +/- 14.5 mm, p = 0.005 respectively). CONCLUSIONS: The MSA, which runs left to the midline of the sacral promontory, and its location can be determined intraoperatively in relation to adjacent visible anatomical structures. The iliac vessels and ureter on the right are significantly closer to the MSA than those on the left. This information may help surgeons performing SC to avoid MSA injury, thus reducing operative morbidity. PMID- 27372947 TI - If you could see what we see, would it bother you? AB - OBJECTIVE: The purpose of our study was to determine whether the anatomic threshold for pelvic organ prolapse (POP) diagnosis and surgical success remains valid when the patient sees what we see on exam. METHODS: Two hundred participants were assigned, by computer-generated block randomization, to see one of four videos. Each video contained the same six clips representative of various degrees of anterior vaginal wall support. Participants were asked questions immediately after each clip. They were asked: "In your opinion, does this patient have a bulge or something falling out that she can see or feel in the vaginal area?" Similarly, they were asked to give their opinion on surgical outcome on a 4-point Likert scale. RESULTS: The proportion of participants who identified the presence of a vaginal bulge increased substantially at the level of early stage 2 prolapse (1 cm above the hymen), with 67 % answering yes to the question regarding bulge. The proportion of participants who felt that surgical outcome was less desirable also increased substantially at early stage 2 prolapse (1 cm above the hymen), with 52 % describing that outcome as "not at all" or "somewhat" successful. CONCLUSION: Early stage 2 POP (1 cm above the hymen) is the anatomic threshold at which women identify both a vaginal bulge and a less desirable surgical outcome when they see what we see on examination. PMID- 27372948 TI - Commentary. PMID- 27372950 TI - The Psychology of Quality of Life. PMID- 27372949 TI - Response. PMID- 27372951 TI - [Not Available]. PMID- 27372952 TI - [Not Available]. PMID- 27372953 TI - Regional Level Influenza Study with Geo-Tagged Twitter Data. AB - The rich data generated and read by millions of users on social media tells what is happening in the real world in a rapid and accurate fashion. In recent years many researchers have explored real-time streaming data from Twitter for a broad range of applications, including predicting stock markets and public health trend. In this paper we design, implement, and evaluate a prototype system to collect and analyze influenza statuses over different geographical locations with real-time tweet streams. We investigate the correlation between the Twitter flu counts and the official statistics from the Center for Disease Control and Prevention (CDC) and discover that real-time tweet streams capture the dynamics of influenza cases at both national and regional level and could potentially serve as an early warning system of influenza epidemics. Furthermore, we propose a dynamic mathematical model which can forecast Twitter flu counts with high accuracy. PMID- 27372954 TI - Multimodality Imaging Guidelines of Patients with Transposition of the Great Arteries: A Report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance and the Society of Cardiovascular Computed Tomography. PMID- 27372955 TI - Your New President and Value of Teamwork. PMID- 27372956 TI - Learning a New Skill Set. PMID- 27372958 TI - A Piece of Our Mind/The Many Faces of FASE. PMID- 27372957 TI - Training in Perioperative Echocardiography: Time to Think Outside the Box. PMID- 27372959 TI - Incidence of malignant mesothelioma in Aboriginal people in Western Australia. AB - OBJECTIVES: To describe the incidence of malignant mesothelioma (MM) in Aboriginal people in Western Australia (WA) and determine the main routes of exposure to asbestos in this population. METHODS: All MM cases in Western Australia, as well as the primary source of asbestos exposure, are recorded in the WA Mesothelioma Register. Aboriginal cases up to the end of 2013 were extracted from the register and compared with non-Aboriginal cases with respect to the primary means/source of exposure. Age-standardised incidence rates for each decade from 1980 were calculated for both Aboriginals and non-Aboriginals. Age-standardised mortality rates were calculated for the period 1994-2008 and compared with international rates. RESULTS: There were 39 cases (77% male) of MM among WA Aboriginal people. Twenty-six (67%) were a direct result of the mining of crocidolite at Wittenoom and the subsequent contamination of the surrounding lands. Of the non-Aboriginal MM cases (n = 2070, 86.3% male), fewer than 25% can be attributed to Wittenoom. Aboriginals had consistently higher 10-year incidence rates than non-Aboriginals and, when compared to world populations, the highest mortality rate internationally. CONCLUSION: When incidence rates in Aboriginal people are compared with non-Aboriginal people, the Wittenoom mining operation has had a disproportionate effect on MM incidence in the local Aboriginal population. PMID- 27372960 TI - Clinical nurses' knowledge and attitudes toward patients with epilepsy. AB - BACKGROUND: Insufficient knowledge and negative attitudes of clinical nurses regarding epilepsy may affect the quality of health care for patients with epilepsy. AIM: The aim of this study was to evaluate knowledge and attitudes of nurses working at a university hospital located in eastern Turkey regarding epilepsy. METHOD: The descriptive study was conducted with 85 nurses working at the internal medicine clinics at Yakutiye Research Hospital in Erzurum, Turkey in March 2014. The data comprised the personal information form, epilepsy knowledge scale, and epilepsy attitude scale. RESULTS: Clinical nurses obtained a mean score of 12.62+/-2.77 on the epilepsy knowledge scale and 55.43+/-6.59 on the epilepsy attitude scale. There was a significant difference between the educational status of nurses and mean scores on the epilepsy knowledge scale and epilepsy attitude scale (P<0.05). There was a positive, significant correlation between knowledge scores and attitude scores of clinical nurses regarding epilepsy (r=0.227, P<0.05). In addition, more than half of nurses (57.6%) knew that epileptic seizures would not pose a danger to other people. Unfortunately, approximately one-third of clinical nurses (36.5%) believed that epilepsy was incurable. CONCLUSION: As a result of the study, it was determined that nurses had a moderate level of knowledge regarding epilepsy, and they generally displayed a positive attitude, but it was not sufficient. In addition, more knowledge was associated with a more positive attitude. PMID- 27372961 TI - Suicide among people with epilepsy: A population-based analysis of data from the U.S. National Violent Death Reporting System, 17 states, 2003-2011. AB - OBJECTIVE: This study analyzed suicide data in the general population from the U.S. National Violent Death Reporting System (NVDRS) to investigate suicide burden among those with epilepsy and risk factors associated with suicide and to suggest measures to prevent suicide among people with epilepsy. METHODS: The NVDRS is a multiple-state, population-based, active surveillance system that collects information on violent deaths including suicide. Among people 10years old and older, we identified 972 suicide cases with epilepsy and 81,529 suicide cases without epilepsy in 17 states from 2003 through 2011. We estimated their suicide rates, evaluated suicide risk among people with epilepsy, and investigated suicide risk factors specific to epilepsy by comparing those with and without epilepsy. In 16 of the 17 states providing continual data from 2005 through 2011, we also compared suicide trends in people with epilepsy (n=833) and without epilepsy (n=68,662). RESULTS: From 2003 through 2011, the estimated annual suicide mortality rate among people with epilepsy was 16.89/100,000 per persons, 22% higher than that in the general population. Compared with those without epilepsy, those with epilepsy were more likely to have died from suicide in houses, apartments, or residential institutions (81% vs. 76%, respectively) and were twice as likely to poison themselves (38% vs. 17%) (P<0.01). More of those with epilepsy aged 40-49 died from suicide than comparably aged persons without epilepsy (29% vs. 22%) (P<0.01). The proportion of suicides among those with epilepsy increased steadily from 2005 through 2010, peaking significantly in 2010 before falling. SIGNIFICANCE: For the first time, the suicide rate among people with epilepsy in a large U.S. general population was estimated, and the suicide risk exceeded that in the general population. Suicide prevention efforts should target people with epilepsy 40-49years old. Additional preventive efforts include reducing the availability or exposure to poisons, especially at home, and supporting other evidence-based programs to reduce mental illness comorbidity associated with suicide. PMID- 27372962 TI - Impact of an educational comic book on epilepsy-related knowledge, awareness, and attitudes among school children in Ethiopia. AB - INTRODUCTION: Epilepsy is of worldwide public health importance because it is common, often accompanied by physical and cognitive disabilities, and is widely stigmatized. The incidence of epilepsy in Ethiopia was reported to be 64/100,000 population and a prevalence of 520/100,000 population. A minority of subjects is treated, and religious and sociocultural beliefs influence the nature of treatment and care. One approach to support the development of positive attitudes toward individuals with disabilities is through the use of comics. Comics have been effective in creating awareness and educating about epilepsy. MATERIAL AND METHODS: We conducted a cross-sectional study among randomly selected students from two preparatory schools (one from a city and the other from a rural area) in June 2014. We collected information using a structured KAP questionnaire before and after reading a comic book. The comic book relevance was assessed by 40 health professionals. RESULT: One hundred sixteen students from urban and 110 from rural high schools were enrolled in the present study with an age distribution of 31.9% in 16-17years, 48.7% in 18-19years, and 19.5% in 20+years. Thirty percent of the urban school was male compared with sixty-five percent of the rural school. The comic book was recommended as useful educational material to be distributed among school children by 90% of interviewed health professionals (internists, neurologist, psychiatrists, residents, GPs, and nurses). CONCLUSION: The comic book was appreciated by the Ethiopian high school students. After brief exposure to the comic book, students could extract a great deal of information, it could change misconceptions and provide correct information about epilepsy, and can be an effective approach to epilepsy awareness creation. Health professionals found the comic book to be very informative and recommended its distribution to students, teachers, nurses, libraries, and community/religious leaders. Illustrations were Ethiopian oriented. PMID- 27372963 TI - Prevalence and correlates of Mycoplasma genitalium infection among prostatitis patients in Shanghai, China. AB - Background: Mycoplasma genitalium (M. genitalium) has been shown to be involved in chronic non-gonococcal urethritis (NGU). However, the prevalence and determinants of this emerging sexually transmissible infection among prostatitis patients remain obscure. Methods: Two hundred and thirty-five patients diagnosed with prostatitis and 152 health controls from sexually transmitted diseases (STD) clinics in Shanghai, China, were selected. M. genitalium was detected in the initial voided urine (VB1), midstream of urine (VB2), expressed prostatic secretion (EPS) and the opening urine after massage (VB3) by quantitative polymerase chain reaction (Q-PCR) targeting the Mycoplasma genitalium adhesion protein (MgPa). An infection of the prostate was considered positive if a uropathogen was found only in the EPS sample or VB3, or if it was at least four fold greater in EPS or VB3 than in VB1 or VB2. The prostatitis patients with M. genitalium infection were treated with azithromycin. Results: The prevalence of M. genitalium infection was significantly higher among the prostatitis group than the control group (10 vs 3%, P = 0.005). Among the prostatitis group, M. genitalium infection was significantly associated with those patients who received treatment for genitourinary infection previously than those patients who did not (17 vs 6%; adjusted OR, 4.011; 95% CI, 1.562-10.300). The symptoms were totally or partially improved in 83% per cent (19/23) of prostatitis patients with M. genitalium, positive in EPS and M. genitalium turned negative after azithromycin treatment. Conclusions: M. genitalium was prevalent in the patients with prostatitis, particularly in those who received ineffective antibiotic treatment for the bacterium, and was identified as having a significant association of prostatitis. PMID- 27372964 TI - Assessing patients' and GPs' ability to recognise overweight and obesity. AB - OBJECTIVE: To assess the ability of GPs and patients to recognise overweight and obesity, determine factors associated with accurate weight perception, and identify methods used by patients and GPs to manage patient overweight and obesity. METHODS: Data were collected in a substudy of the BEACH research program (a continuous, randomised, national cross-sectional survey of general practice activity in Australia). RESULTS: Of 1,599 sampled adult patients, 31.5% were overweight, 23.7% obese and 4.7% morbidly obese. One in four (26.8%) overweight/obese patients (BMI >=25.0) did not consider themselves overweight. There was an association between patient age and sex and accurate weight perception. Overweight/obese females and those aged 45-64 years were most likely to recognise their overweight. GPs correctly identified 60.8% of overweight patients, but underestimated 35.7% as normal weight. They also identified 60.0% of obese patients, but incorrectly categorised 37.0% as overweight and 3.0% normal weight. There was no association between GP age and sex and accurate weight perception. CONCLUSIONS: Patients' and GPs' perception of weight can often be inaccurate, with many not recognising overweight and obesity. Improvement in recognition of overweight and obesity may increase management and encourage early intervention to prevent disease associated with these weight problems. PMID- 27372965 TI - No official identity: a data linkage study of birth registration of Aboriginal children in Western Australia. AB - OBJECTIVE: Evidence of identity, particularly a birth certificate, is essential to access many rights. However, the births of many Aboriginal Australians are not registered when they are infants. We examined factors related to birth registration among Western Australian children born to Aboriginal mothers. METHODS: All births to Aboriginal mothers in the Midwives Notification System in Western Australia (WA) from 1980 to 2010 were linked to birth registrations. Associations between registration and maternal and child characteristics were examined for children aged under 16 years in 2012. RESULTS: Among 49,694 births between 1980 and 2010, 18% of those aged under 16 years had unregistered births, compared to 3% of those aged 16-32 years. Unregistered births were most strongly associated with young maternal age at first birth (adjusted odds ratio [AOR] 5.22; 95%CI 3.07-8.86; for 16 years or younger vs 30 years or older, among non smokers), remoteness (AOR 2.17; 95%CI 1.87-2.52; very remote vs major cities), mothers whose own birth was unregistered (AOR 3.00; 95%CI 1.78-5.07) and no private hospital insurance (AOR 0.19; 95%CI 0.11-0.31; insured vs uninsured). CONCLUSIONS: Unregistered births are common among WA Aboriginal children, particularly in disadvantaged families. IMPLICATIONS: Assistance before discharge from hospital may increase birth registrations. PMID- 27372966 TI - BIRC5 Genomic Copy Number Variation in Early-Onset Breast Cancer. AB - BACKGROUND: Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) gene is an inhibitor of apoptosis that expresses in human embryonic tissues but it is absent in most healthy adult tissues. The copy number of BIRC5 has been indicated to be highly increased in tumor tissues; however, its association with the age of onset in breast cancer is not well understood. METHODS: Forty tumor tissues of breast cancer were obtained from Tumor Bank of Cancer Institute, Imam Khomeini Hospital, Tehran, Iran. BIRC5 gene copy number variation (CNV) was evaluated using Multiplex Ligation-dependent Probe Amplification (MLPA) and then compared with the age of onset for each patient. RESULTS: BIRC5 amplification was seen in 17.5% of cases. Also, a significant association was observed between BIRC5 gene amplification and individuals under 40 years of age (P=0.04). CONCLUSION: BIRC5 gene has the potential to be a marker for the detection and prognosis of cancer at an early age. PMID- 27372968 TI - Don't trust this smartphone app to measure your blood pressure. PMID- 27372967 TI - Brief report: Human Papillomavirus (HPV) 6, 11, 16, and 18 Seroprevalence Among Males and Females Entering Military Service During 2011-2012. PMID- 27372969 TI - DASH diet may lower stroke risk. PMID- 27372970 TI - My doctor told me I have stage C heart failure. He wants to start a number of medications. Are all these necessary? PMID- 27372971 TI - study helps affirm evidence of statins' muscle-related side effects. Cleveland Clinic researchers explore statin intolerance, making a strong argument on behalf of patients who complained of muscle pain caused by cholesterol drugs. PMID- 27372973 TI - drink more water to cut calories, fat, and sugar. PMID- 27372972 TI - Dietary nitrate may lower risk of glaucoma. PMID- 27372974 TI - Is diabetes taking a bite out of your teeth? PMID- 27372975 TI - Time to deflate the spare tire. PMID- 27372976 TI - Transmission. Messages need to focus on all types of MSM risk. PMID- 27372977 TI - Prevention. Raltegravir, maraviroc show promise as PrEP drugs in studies. PMID- 27372978 TI - Prevention. Antibody to be tested for effectiveness, safety. PMID- 27372979 TI - Needle exchange. UN report encourages syringe exchanges to reduce HIV. PMID- 27372980 TI - Do you need a depression screening? PMID- 27372981 TI - Couch potato in midlife, smaller brain later? PMID- 27372982 TI - Mammograms identify heart disease risk. PMID- 27372983 TI - Study shows mind-body approaches better than pain relievers for sore backs. PMID- 27372984 TI - Treatment. Tenofovir-resistant HIV increasing in Africa. PMID- 27372985 TI - More research, treatment options to prevent transmission in women. PMID- 27372986 TI - I just turned 65, and I'm increasing concerned about my loss of muscle mass. How can I turn the tide? PMID- 27372987 TI - What are some of the dangers of insect bites, and how can I protect against them? PMID- 27372988 TI - Knee buckling raises the risk of falls. PMID- 27372989 TI - Flavonoids associated with better erectile function. PMID- 27372991 TI - Exercise may improve emotional, physical outcomes of a heart attack. PMID- 27372990 TI - Health conditions for travellers to Saudi Arabia for the pilgrimage to Mecca (Hajj), 2016. PMID- 27372992 TI - Index, Volume 91, 2016, Nos. 1-27. PMID- 27372993 TI - Atrial flutter: why you shouldn't ignore palpitations that linger. PMID- 27372994 TI - Unstable knees may contribute to recurrent falls and injuries. PMID- 27372995 TI - Moderate alcohol consumption may reduce diabetes risk. PMID- 27372996 TI - Getting out of the chair boosts metabolism in postmenopausal women. PMID- 27372998 TI - Test may diagnose prostate cancer more accurately. PMID- 27372997 TI - How long should you take a bisphosphonate for osteoporosis? PMID- 27372999 TI - Men's hearts age differently from women's. PMID- 27373000 TI - Your guide to everyday eating for optimal health. PMID- 27373002 TI - Access to medical records gets a boost. PMID- 27373001 TI - Culinary medicine: a prescription for healthier eating. PMID- 27373004 TI - Downward-dog don'ts. PMID- 27373003 TI - Do you really need that cancer screening? PMID- 27373005 TI - Taming stubborn gout. PMID- 27373006 TI - PSA testing do-overs. PMID- 27373007 TI - Injections beat laser for retinopathy. PMID- 27373008 TI - Are you a DDT daughter? PMID- 27373009 TI - Ringing in a promising tinnitus treatment. PMID- 27373010 TI - Revisions to Exceptions Applicable to Certain Human Cells, Tissues, and Cellular and Tissue-Based Products. Final rule. AB - : The Food and Drug Administration (FDA or Agency or we) is issuing this final rule to amend certain regulations regarding donor eligibility, including the screening and testing of donors of particular human cells, tissues, and cellular and tissue-based products (HCT/Ps), and related labeling. This final rule is in response to our enhanced understanding in this area and in response to comments from stakeholders regarding the importance of embryos to individuals and couples seeking access to donated embryos. PMID- 27373011 TI - Modification of Treatment of Certain Health Organizations. Final regulations. AB - This document contains final regulations that provide guidance to Blue Cross and Blue Shield organizations, and certain other organizations, on computing and applying the medical loss ratio and the consequences for not meeting the medical loss ratio threshold. The final regulations reflect the enactment of a technical correction to section 833(c)(5) of the Internal Revenue Code by the Consolidated and Further Continuing Appropriations Act of 2015. The final regulations affect Blue Cross and Blue Shield organizations, and certain other organizations involved in providing health insurance. PMID- 27373012 TI - International Conference on Harmonisation; Electronic Transmission of Postmarket Individual Case Safety Reports for Drugs and Biologics, Excluding Vaccines; Availability of Food and Drug Administration Regional Implementation Specifications for ICH E2B(R3) Reporting to the Food and Drug Administration Adverse Event Reporting System. Notice of Availability. AB - The Food and Drug Administration (FDA) is announcing the availability of its FDA Adverse Event Reporting System (FAERS) Regional Implementation Specifications for the International Conference on Harmonisation (ICH) E2B(R3) Specification. FDA is making this technical specifications document available to assist interested parties in electronically submitting individual case safety reports (ICSRs) (and ICSR attachments) to the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). This document, entitled "FDA Regional Implementation Specifications for ICH E2B(R3) Implementation: Postmarket Submission of Individual Case Safety Reports (ICSRs) for Drugs and Biologics, Excluding Vaccines" supplements the "E2B(R3) Electronic Transmission of Individual Case Safety Reports (ICSRs) Implementation Guide--Data Elements and Message Specification" final guidance for industry and describes FDA's technical approach for receiving ICSRs, for incorporating regionally controlled terminology, and for adding region-specific data elements when reporting to FAERS. PMID- 27373013 TI - Medicare Program; Medicare Clinical Diagnostic Laboratory Tests Payment System. Final rule. AB - This final rule implements requirements of section 216 of the Protecting Access to Medicare Act of 2014 (PAMA), which significantly revises the Medicare payment system for clinical diagnostic laboratory tests. This final rule also announces an implementation date of January 1, 2018 for the private payor rate-based fee schedule required by PAMA. PMID- 27373014 TI - Penalty Inflation Adjustments for Civil Money Penalties. Interim Final Rule. AB - In accordance with the Federal Civil Penalties Inflation Adjustment Act of 1990, as amended by the Debt Collection Improvement Act of 1996, and further amended by the Bipartisan Budget Act of 2015, section 701: Federal Civil Penalties Inflation Adjustment Act Improvements Act of 2015, this interim final rule incorporates the penalty inflation adjustments for the civil money penalties contained in the Social Security Act PMID- 27373015 TI - Medical Devices; General and Plastic Surgery Devices; Classification of the Electrosurgical Device for Over-the-Counter Aesthetic Use. Final order. AB - The Food and Drug Administration (FDA) is classifying the electrosurgical device for over-the-counter aesthetic use into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language for the electrosurgical device for over-the-counter aesthetic use's classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. PMID- 27373016 TI - Revised Medical Criteria for Evaluating Neurological Disorders. Final rule. AB - We are revising the criteria in the Listing of Impairments (listings) that we use to evaluate disability claims involving neurological disorders in adults and children under titles II and XVI of the Social Security Act (Act). These revisions reflect our program experience; advances in medical knowledge, treatment, and methods of evaluating neurological disorders; comments we received from medical experts and the public at an outreach policy conference; responses to an advance notice of proposed rulemaking (ANPRM); and public comments we received in response to a Notice of Proposed Rulemaking (NPRM) and a Federal Register notice that reopened the NPRM comment period. PMID- 27373017 TI - Finally, working on a health system for 21st-century Canadians. PMID- 27373018 TI - Did you know.... PMID- 27373020 TI - Examining medical assistance in dying from all sides. PMID- 27373019 TI - Everything that grows, changes. PMID- 27373021 TI - Introduction to psychometric measurement. PMID- 27373022 TI - Indigenous Nurse Leaders Share Success Stories. PMID- 27373023 TI - Ready to Embrace the Future? PMID- 27373024 TI - Innovative Leadership Program Expands Reach. PMID- 27373025 TI - Overcoming Barriers to Access, One Community Support at a Time. PMID- 27373026 TI - An oral cancer therapy nurse navigator role. PMID- 27373027 TI - In tune with living well. PMID- 27373028 TI - A profession looking to gain more prestige through academia. PMID- 27373029 TI - [Short-term complications in reconstruction of the postoperative defects with free jejunum graft in patients with pharyngeal, laryngeal or cervical esophageal cancers]. AB - OBJECTIVE: To explore the clinical effects and short-term complications of using free jejunum graft (FJG) to reconstruct the defects by resections of pharyngeal, laryngeal or cervical esophageal cancers. METHOD: Fifty-eight cases of pharyngeal, laryngeal or cervical esophageal cancers were reconstructed with FJG. All cases were analyzed retrospectively. RESULT: The success rate of FJG transplantations was 91.4% (53/58). The incidence of post-operative short-term complication was 43.1% (25/58), which was not related to age or BMI. The most common complication was anastomotic leakage (18.9%), which was not related to per operative radiation therapy. However, BMI > 25 cases had significantly higher incidence of anastomotic leakage than BMI <= 25 cases (P = 0.009). The second and third most common complications were respiratory system complications (10. 3%) and FJG necrosis (8. 6%). Para-operative death rate was 3.4% (2/58). Two-year overall survival rates of hypopharyngeal cancer and cervical esophageal cancer were 49% and 67% respectively. The group with no short-term complications had a slightly better survival rate than the group with short-term complications from the Kaplan-Meier curve, but there was no significant difference (P = 0.103). CONCLUSION: FJG is ideal to reconstruct cervical digestive tract circumferential defects with a high success rate and a low mortality. However, the post-operative complication rate is high. Intensive observation, early detection and timely treatment of complications are crucial. PMID- 27373030 TI - [Application of narrow band imaging in early diagnosis of pharyngolaryngeal tumors]. AB - OBJECTIVE: To investigate the application value of narrow band imaging (NBI) in early diagnosis of pharyngolaryngeal tumors. METHOD: A total of 106 patients received NBI endoscopy in the endoscopic diagnosis. Lesions found under the white light endoscopy mode and NBI endoscopy mode were compared in the morphology of capillaries on lesiorn surface and the clarity of lesion rim. Biopsy was performed in suspected areas with those two endoscopies for the lesions found under white-light endoscopy and NBI endoscopy, the morphology of capillaries on the surface of lesion and the clarity of lesion boundary were compared between both. Biopsy was performed for suspected areas under two modes, and specimens were preserved in 10% formaldehyde for pathological examination. The characteristic, position and endoscopic diagnosis under two modes were recorded. All the patients underwent corresponding laryngeal tumor resection according to the histopathological result of biopsy, and the histopathological result of resected tissues was taken as the gold standard for diagnosis. The biopsy detection rate and biopsy correct detection rate of malignant lesions in two groups were calculated and statistical compared. RESULT: The diagnostic accuracy under white-light mode was 75.47%, while that under NBI mode was 96.23%, and the difference between them was statistically significant (chi2 = 18.375, P < 0.01). The biopsy correct detection rate under white-light mode was 82.08%, while that under NBI mode was 95.28%, and the difference between them was statistically significant (chi2 = 12.071, P < 0.01). The correct detection rate of malignant tumor under white-light mode was 48.15%, while that under NBI mode was 92.59%, and the difference between them was statistically significant (chi2 = 10.083, P < 0.01). CONCLUSION: Using NBI endoscopy to observe the morphological changes of capillaries on the pharyngolaryneal mucosa surface can increase the detection rate of early pharyngolaryngeal tumors, so it is worth to be widely applied. PMID- 27373031 TI - [Acoustic analysis in patients with unilateral arytenoid dislocation and unilateral vocal fold paralysis]. AB - OBJECTIVE: To analysis the acoustic characteristics in patients with unilateral arytenoid dislocation and unilateral vocal fold paralysis, and evaluate the application value of acoustic analysis technique in these two diseases. METHOD: The voice signals of sustained vowel /a/ were measured using the software MDVP in 50 healthy adults and 67 patients with unilateral vocal cord movement disorders. The acoustic parameters (jitter, shimmer, NHR and F0) were analyzed. All patients were divided into arytenoid dislocation group (36 cases) and vocal fold paralysis group (31 cases) through the laryngeal electromyography. All groups were divided into male and female group again. The acoustic characteristics between the two experimental groups and normal control groups were observed and compared. Results were analyzed using Rank sum test. RESULT: (1) In both male or female groups, there were significant differences in jitter and shimmer between two experimental group and control group. In both male or female groups, there were significant differences in NHR between arytenoid dislocation group and control group. There were no significant differences in NHR between vocal fold paralysis group and control group. Except for the male vocal fold paralysis group, there were significant differences in F between the other experimental groups and control groups. (2) In both male or female groups, there were no significant differences in jitter and shimmer between vocal fold paralysis group and arytenoid dislocation group. There were significant differences in NHR. CONCLUSION: The acoustic parameters are effective parameters to measure the voice quality of patients with unilateral arytenoid dislocation and unilateral vocal fold paralysis. NHR is the most sensitive parameter in the distinction of vocal cord paralysis and arytenoid dislocation. PMID- 27373032 TI - [The value of otolith function test in the prognosis of sudden sensorineural hearing]. AB - OBJECTIVE: To evaluate the characteristics and prognosis of sudden sensorineural hearing loss through vestibular evoked myogenic potentials. METHOD: Fifty patients with unilateral sudden hearing loss underwent an ear test battery, including audiometry, cervical vestibular evoked myogenic potential (cVEMP) and ocular vestibular evoked myogenic potential(oVEMP). The cVEMP and oVEMP in patients with sudden sensorineural hearing loss were investigated. Their associations with initial hearing threshold, the type of audiogram, the results of coloric test and hearing recovery were also accessed. RESULT: After one-month treatment, the average threshold declined significantly in affected ears, with normal VEMP rates improved significantly (P < 0.05). Initial hearing threshold and hearing recovery were significantly associated with the results of coloric test and the results of VEMP test (P < 0.05). CONCLUSION: Our study indicated that vestibular evoked myogenic potential examination was not only a useful additional diagnostic tool in the neurotological evaluation of patients suffering sudden hearing loss, but also very valuable in the prognosis of sudden sensorineural hearing loss. PMID- 27373033 TI - [The role of Th9, Th17 and Treg cells on pathogenesis of nasal polyps]. AB - OBJECTIVE: To investigate the expression levels of Th9, Th17 and Treg cells in peripheral blood of patients with chronic rhinosinusitis with nasal polyps (CRSwNP), and explore the role of Th9, Th17 and Treg cells in the progression of CRSwNP. METHOD: Forty-six cases with CRSwNP served as an experimental group, while 22 cases with simple nasal bleeding or nasal septum deviation served as a control group. The peripheral blood of patients in both groups was collected and analyzed. (1) Using flow cytometry (FCM) to detect the expression rates of Th9, Th17 and Treg cells in peripheral blood. (2) Using qRT-PCR to detect the expression of relevant transcription factor of Th9, Th17 and Treg cells (IL 9mRNA, PU. 1, IRF-4, RoRc, and Foxp3). (3) Using SPSS16.0 to analyse the differentiations and the revelance among these three cells. RESULT: (1) The expression rates of Th9 and Th17 cells in patients with CRSwNP (1.29% +/- 0.18%, 4.03% +/- 0.69%) was higher than the control group (0.45% +/- 0.14%, 1.35% +/- 0.26%). But the expression rates of Treg cells in the experimental group (2.98% +/- 0.13%) was significantly lower than the control group (5.44% +/- 0.57%). The differences were statistically significant (P < 0.05). (2) The expression of revelant transcription factor (IL-9mRNA, PU.1, IRF-4, RoRc) in NP group was also higher than the control group. The expression of Foxp3 in the control group was higher than NP, the differences both were statistically significant (P < 0.05). (3) The difference between Th9 and Th17 in patients with NP was not significant (P > 0.05), and the negative correlation was found between Th17 and Treg (r = 0.549, P < 0.05). CONCLUSION: The high expression level of Th9 and Th17 cells might promote the development of NP, whereas the low expression level of Treg cells might further aggravate the occurrence of NP. The main function of the imbalance of Th17/Treg cells may be immune regulation in the pathogenesis of nasal polys. PMID- 27373034 TI - [Taxane-cisplatin-fluorouracil as induction chemotherapy for advanced head and neck cancer: a Meta-analysis of the efficacy and safety]. AB - OBJECTIVE: To systematically review the efficacy and safety of taxane, cisplatin, and fluorouracil (Tax-PF) as induction chemotherapy for advanced head and neck cancer. METHOD: Literature about the efficacy and safety of Taxane-cisplatin fluorouracil as induction chemotherapy for advanced head and neck cancer was retrieved from digital databases of PubMed, Embase, SpringerLink, MEDLINE and the Cochrane Library before February 2015. Data extraction and quality assessment of included studies were conducted by two reviewers independently. Stata 13.0 was then used to perform Meta-analysis. RESULT: A total 7 randomized controlled trials involving 2,702 were included. The 3-year OS rate [HR = 1.14, 95% CI (1.03, 1.25), P < 0.01], 3-year PFS rate [HR = 1.24, 95% CI (1.08, 1.43), P < 0.01], 5-year OS rate [HR = 1.30, 95% CI (1.09, 1. 55), P < 0. 01], 5-year PFS rate [HR = 1.39, 95% CI (1.14, 1.70), P < 0.01] and ORR to chemotherapy [OR = 1.66, 95% CI (1.35, 2.05), P < 0.01] of the patients in the Tax-PF group were statistically superior to those in the PF group. In terms of toxicities, the incidence of febrile neutropenia [OR = 2.36, 95% CI (1.62, 3.46), P < 0.01], alopecia [OR = 8.22, 95% CI (3.99, 16.92), P < 0.01], diarrhea [OR = 1.57, 95% CI (1.05, 2.36), P< 0.05] and leucopenia [OR = 2.79, 95% CI (1.86, 4.21), P < 0.01] was higher in the Tax-PF group than that in the PF group. CONCLUSION: The Tax-PF induction chemotherapy improved PFS and OS, and the ORR was better as compared to PF-based therapy regimens at the cost of a higher incidence of adverse events. PMID- 27373035 TI - [Association between MKK4 promoter-1304T/G polymorphism and genetic susceptibility in sporadic nasopharyngeal carcinoma]. AB - OBJECTIVE: To investigate the association between-1304T/G polymorphism in the promoter of MKK4 gene and the susceptibility in sporadic nasopharyngeal carcinoma. METHOD: MKK4-1304T/G genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 90 NPC cases and 30 healthy controls. RESULT: The number of nasopharyngeal carcinoma patients carrying with TG+GG genotype was much higher than those of controls (82.2% vs 66.7%, chi2 =10.076, P < 0.05). Analysis showed that compared with the-1304TT genotype, -1304TG heterozygous reduced risk of nasopharyngeal carcinoma 0.56 fold (95% CI = 0.164-1.178, P < 0.01) and-1304GG lower 0.58 fold (95% CI = 0.126 1.381, P < 0.01), TG+ GG genotype variation risk of nasopharyngeal carcinoma decreased 0.72 fold (95% CI = 0.105-0.753, P < 0.01). CONCLUSION: MKK4 gene 1304TG genotype can reduce risk of nasopharyngeal carcinoma, and it may be an independent protection factor in sporadic nasopharyngeal carcinoma. PMID- 27373036 TI - [Efficient evaluation of standardized specific immunotherapy in personalized maintenance phase to patients of allergic rhinitis]. AB - OBJECTIVE: To explore the efficacy of individualized subcutaneous immunotherapy (SCIT) in allergic rhinitis(AR) maintain phase. METHOD: Compare nasal symptom scores (VAS) and special disease scale--nasal conjunctivitis quality of life questionnaire(RQLQ) score after 3 years treatment to evaluate the therapeutic effect of each group and the level of improving patients quality of life. Take patients' blood to detect the serum level of IL-10 by enzyme linked immunosorbent test (enzyme linked immunosorbent assay). RESULT: After 3 years treatment, there was no difference of VAS between the conventional SCIT group and the individualized SCIT group. ELISA results showed that the level of IL-10 was significantly higher in the drug symptomatic treatment group than that in the healthy group, the levels of IL-10 were significantly lower in the conventional SCIT group and the individualized SCIT group than that in the healthy group, but there was no difference between the conventional SCIT and the individualized SCIT group. CONCLUSION: After 3 years treatment, there was no difference between conventional and individualized SCIT groups. But the efficacy of the conventional and individualized SCIT groups were significantly better than that in the drug symptomatic treatment group. PMID- 27373037 TI - [Effectiveness of different click stimuli in diagnosing superior canal dehiscence using cervical vestibular evoked myogenic potentials]. PMID- 27373038 TI - [Prevalence of obstructive sleep apnea-hypopnea syndrome in adults aged over 60 yeaes in dongying city]. AB - OBJECTIVE: To survey the prevalence of obstructive sleep apnea-hypopnea syndrome(OSAHS) in adults aged over 60 years in Dongying city,and analyze the risk factors and the extent of damage to the quality of life for the elderly to provide the basis for prevention and treatment of OSAHS people. METHOD: One thousand subjects were derived from a random cluster sampling in seven districts of Dongying city:they were asked to answer the questions from questionnaires. According to the questionnaire scoring, 100 subjects in high-risk group were selected randomly to make polysomnography monitoring for a whole night,so that the prevalence of the disease was calculated and the related risk factors were analyzed; elderly patients diagnosed with OSAHS were asked to assess the quality of life assessment questionnaire by face to face to understand the quality of life dimensions injury. RESULT: The actual number of completed surveys was 934, and the efficiency was 93.4%. The estimated prevalence of OSARS in elder people defined by apnea-hypopnea index (AHI >= 5) was 32.5%; Multivariate analysis revealed that age smoking, family snoring,neck circumference, waist circumference, and abnormality of the upper airway were respectively independent risk factors of OSAHS,and the abnormalities of the upper airway had the most obvious impact on AHI. The damage caused by OSAHS to the quality of life for elderly people followed their daily work life, social relationships, symptoms, alertness, emotional, general health, symptoms. CONCLUSION: The estimated prevalences of OSAHS in elder people were high. Actively promoting good habits to older people, weight loss, early detection and correct upper airway abnormalities may reduce the estimated prevalence of OSAHS. In the treatment process, the patient's physician should pay attention to their emotional and groom their psychological problems to improve the quality of life in elder people. PMID- 27373039 TI - [Effect of CPAP therapy on sleep quality and quality of life in patients with moderate or severe OSAHS]. AB - OBJECTIVE: To assess the effect of CPAP therapy on sleep quality and quality of life in patients with moderate or severe OSAHS. METHOD: Seventy-two patients diagnosed as OSAHS by polysomnography (PSG) were assigned to receive CPAP therapy for 3 months. At baseline and three months after treatment patients underwent polysomnography (PSG). Analyze the results of PSG, sleep quality, excessive daytime sleepiness, quality of life and the general well-being. RESULT: The lowest average oxygen saturation and the average blood oxygen saturation improved significantly after CPAP therapy, and the longest sleep apnea time and AHI decreased obviously (P < 0.01). Except body pain, the other seven dimensions of SF-36 improved obviously (P < 0.01); ESS, PSQI and GWB also improved (P < 0.05). CONCLUSION: For patients with moderate or severe OSAHS, CPAP therapy can obviously improve the sleep quality, excessive daytime sleepiness, improve patients' life quality and the general well-being. PMID- 27373040 TI - [Relationship between Testin expression and clinicopathological characteristics in nasopharyngeal carcinoma patients]. AB - OBJECTIVE: To investigate the expression of Testin gene, and analyze its possible relationship with the clinicopathological features of human nasopharyngeal carcinoma. METHOD: The expression of Testin in nasopharyngeal carcinoma tissues were detected by immunohistochemistry methods, semi-quantitative reverse transcription polymerase chain reaction and Western blot. The correlations of Testin to clinicopathologic features of nasopharyngeal carcinoma were analyzed. RESULT: The positive expression rate of Testin in NPC biopsy tissue was 37.8% (17/ 45), while it was 88.9% (40/45) in the normal tissue; The expression of Testin mRNA was significantly lower than that in the normal tissue (P < 0.01); The expression levels of Testin protein in the NPC biopsy tissue by Western blot were lower than that in the normal tissue (P < 0.01); The expression of Testin in the tumor tissue had no significant correlation with sex, age (P > 0.05); but it had significant correlation with lympho node metastasis, distant metastasis and differentiation degree. CONCLUSION: The decreased expression of Testin gene may play an importmant role in the development of nasopharyngeal carcinoma. And thus Testin gene might be a novel candidate of tumor-suppressor. It may be an objective marker for prognostic factor and malignant level for nasopharyngeal carcinoma. PMID- 27373041 TI - [Combined inhibition of STAT3 and HIF-1alpha for enhancement of chemosensitivity in the model of human laryngeal squamous cacinoma in nude mice]. AB - OBJECTIVE: To investigate the effects of combined inhibition of signal transducer and activator of transcription 3 (STAT3) and hypoxia-inducible factor-1alpha (HIF 1alpha) in the enhancement of chemosensitivity of the model of human laryngeal squamous cacinoma in nude mice. METHOD: Model nude mice were divided into six groups randomly: control group(A) , cisplatin group(B) , cisplatin and AG490 group(C) , cisplatin and HIF-1alpha-/- group (D), cisplatin combined AG490 and HIF-1alpha-/- group (E), HIF-1alpha-/- group (F) (only in calculating tumor inhibition rate). 3mg/kg cisplatin was administered by peritoneal injection for 3 days. Then cisplatin and 10 mg/kg AG490 were administered every other day for 12 days. The expression of Ki67 and HIF-1alpha was detected by immunocytochemical method. Western blot was used to detect the expression of p-STAT3. RESULT: The expression of HIF-1alpha in group C and group D were lower than that in group B, and there were significant difference respectively (t1 = 2.782, t2 = 3.873, P < 0.05); The expression of HIF-1alpha in group E was lower than that in group C and group D respectively, and there were significant difference respectively (t1 = 6.140, t2 = 3.667, P < 0.01). The expression level of p-STAT3 in group C was markedly lower compared with that in group B, and there were significant difference between them (t = 17.840, P < 0.01); There were no difference between the expression level of p-STAT3 in group D and that in group B (t = 0.038, P > 0.05); The expression level of p-STAT3 in group E was significantly lower compared with that in group C and group D respectively (P < 0.01). Tumor inhibition rate of group E was higher than that in group B, group C , as well as group D respectively and there were significant difference respectively (t1 = 5.509, P < 0.01; t2 = 3.422, P < 0.05; t3 = 2.718, P < 0.05 ). Ki67 index of group E was lower than that in group B, group C as well as group D respectively and there were significant difference respectively(t1 = 8.307, P < 0.01; t2 = 3.736, P < 0.05; t3 = 4.524, P < 0.01). CONCLUSION: Combined inhibition of STAT3 and HIF-1alpha could enhance chemo-sensitivity in the model of human laryngeal squamous cacinoma in nude mice. PMID- 27373042 TI - [The significance of lymph node dissection in the VI area of cN0 thyroid papillary carcinoma]. AB - OBJECTIVE: The significance of lymph node dissection in the VI area of cN0 thyroid papillary carcinoma. METHOD: Collect 150 cases of patients diagnosed with cNO thyroid papillary carcinoma and they were performed thyroid gland lobe and isthmic portion excision including lateral VI area lymph node cleaning. The specimens were pathologic examined to determinate the size, the position, invasion of thyroid papillary carcinoma,the number and metastasis of lymph node, etc. RESULT: In the 150 patients performed the lymph node VI area groups cleaning, 93 cases had VI area of lymph node metastases, so the transfer rate was 62.0%. In the VI area, metastasis rate of tracheal side lymph nodes was 62.0% (93/150), lymph node before throat group was 4.67% (7/150), lymph node before trachea group was 3.33% (5/150), lymph nodes near the trachea laryngeal recurrent nerve ventral group was 52.0% (78/150), and next to the trachea laryngeal recurrent nerve dorsal lymph node group was 21.33% (32/ 150). CONCLUSION: In CN0 thyroid papillary carcinoma, VI zone of lymph node metastasis rate is high, and region VI lymph node metastasis rate from high to low in order for: paratracheal lymph node, prelaryngeal lymph node, pretracheal lymph node. The metastasis rate of paratracheal throat back nerve ventral lymph node was the highest in central lymph node. PMID- 27373043 TI - [The operation-effect analysis of 8 cases of the first branchial fistula through Epidural catheter]. PMID- 27373044 TI - [The application of ligaSure and loups in the precise surgery of large benign thyroid tumor]. PMID- 27373045 TI - [Application of fibroptic-bronchoscope for intubation in high-risk epiglottic cyst surgery]. PMID- 27373046 TI - [Ectopic internal carotid artery of the oropharynx: two cases report]. AB - Ectopic internal carotid artery (ICA) is a very rare congenital variation. Unless the diagnosis is made before neck or tonsil surgery, massive hemorrhage and even death may result from injury to the vessel. Therefore, knowledge of the presence of ectopic ICAs may be important. We report two cases suffering from dysphagia associated with ectopic ICA manifesting itself as a pulsative protruding of the right lateral wall of the oropharynx. PMID- 27373047 TI - [The resection of the huge mediastinal schwannoma by the jugulal approach: one case report]. AB - Neurogenic tumors located in the posterior mediastinum, generally require surgery which be confronted with greater risk,therefore, to design the best surgical approach and surgical methods is essential. A 67-year-old female patient had pharyngeal foreign body sensation and dysphagia. Thyroid ultrasound showed the right thyroid had a little nodule, and the left thyroid had a hypoechoic lumps. Neck enhanced CT showd mediastinal mass, esophageal tumor origin or stromal tumor? We used the jugular approach to resect the tumor which eventually diagnosed as schwannoma. The meditational benign tumor with an envelope easy to peel can employ the jugular approach to resect it completely. PMID- 27373048 TI - [Embryonal rhabdomyosarcoma of nasopharyngeal: a case report]. AB - This case reports of nasopharyngeal embryonal rhabdomyosarcoma mainly for a stuffy nose, runny nose with blood, and without typical clinical manifestations. Electronic laryngoscopy tip: nasopharyngeal neoplasm. MRI tip: nasopharyngeal carcinoma. By pathological and immunohistochemical examinations, it finally was diagnosed with nasopharyngeal embryonal rhabdomyosarcoma. PMID- 27373049 TI - [The research progress of Treacher Collins syndrome]. AB - Treacher Collins syndrome (TCS, OMIM 154500), also known as Franceschetti-Klein syndrome, is a rare disorder that affects the first and second branchial arches. The estimated incidence is 1/50 000 live births. Mutations in TCOF1 (78%-93%) and POLR1C or POLR1D (8%) cause the disease. Most of TCS cases are inherited in a dominant pattern, while a small proportion are inherited in a recessive pattern. TCS has a variable phenotype with typical clinical characteristics including downward-slant of palpebral fissure, malar hypoplasia, mandibular hypoplasia and microtia. TCS management is a multidisciplinary affair, as interventions range from reconstructive to psychosocial. For hearing rehabilitation, TCS patients may have the choices of BAHA, ponto, vibrant soundbridge or bonebridge implantation. In this review, we summarize the TCS clinical malformations, diagnosis, genetics, management and auditory rehabilitation. PMID- 27373050 TI - [Advance research on the pathogenesis of middle ear cholesteatoma]. AB - Cholesteatoma is a non-neoplastic, keratinizing lesion, characterized by the proliferation of epithelium with aberrant micro-architecture into the middle ear or mastoid cavity. The exact pathogenic molecular mechanisms behind the formation and propagation of cholesteatoma remain unclear. Without timely detection and intervention, cholesteatomas can become dangerous and result in numerous intracranial and extracranial complications. In this review, the current researches about inflammatory mediators, enzymatic activity, growth factors, oxidative stress,infection and genetics in acquired cholesteatoma pathogenesis are discussed. PMID- 27373051 TI - [Advances in treatment of congenital posterior choanal atresia]. AB - Congenital posterior choanal atresia is a rare congenital deformity. Due to the influence of nose and face and intellectual development, its preferred surgical treatment. But surgical treatment methods and technology are in dispute. The using of high resolution display systems combine with micro tools can effectively reduce postoperative scarring and adhesion formation which is the key point to prevent restenosis. There is also the focus of controversy whether should place an expansive tube after operation. Currently nasal endoscopic approach has become the first choice for otolaryngologist treating congenital posterior choanal atresia. PMID- 27373052 TI - Editorial: ASET'S Open Letter to Employers. PMID- 27373053 TI - Kathleen Mears Memorial Lecture: Stay Relevant. PMID- 27373054 TI - Contemporaneous Evaluation of Intraoperative Ulnar and Median Nerve Somatosensory Evoked Potentials for Patient Positioning: A Review of Four Cases. AB - Somatosensory evoked potentials (SSEPs) are a valuable tool for assessing changes in peripheral nerve pathways caused by patient positioning during spinal surgeries. These changes, when left undiagnosed, may lead to postoperative neurological sequelae. Why an upper extremity SSEP attenuates due to positioning is not necessarily clear and can be multifactorial, affecting the peripheral nerves or elements of the brachial plexus. A conduction block can occur at any point along the course of the nerve secondary to entrapment, compression, and ischemia. These mechanisms of injury may be caused by extreme body habitus, the length of the procedure, or the patient's metabolic underpinnings. The goal of neuromonitoring for positional injury is to predict and prevent both peripheral nerve and brachial plexus injuries. Using ulnar and median nerve SSEPs contemporaneously may lead to better identification of compromised structures when an SSEP change to one or both of the nerves occurs. The investigators provide four case reports where intraoperative SSEP assessment of contemporaneous ulnar and median nerves prevented postoperative upper extremity neural deficits. PMID- 27373055 TI - Sharp Slow Waves in the EEG. AB - There exists a paucity of data in the EEG literature on characteristics of "atypical" interictal epileptiform discharges (IEDs), including sharp slow waves (SSWs). This article aims to address the clinical, neurophysiological, and neuropathological significance of SSW The EEGs of 920 patients at a tertiary-care facility were prospectively reviewed over a period of one year. Thirty-six patients had SSWs in their EEG. Of these, 6 patients were excluded because of inadequate clinical data. The clinical and neuroimaging data of the remaining 30 patients were then retrospectively collected and reviewed, and the findings were correlated. The data revealed that SSWs were rare and age-related EEG events occurring primarily in the first two decades of life. All patients with SSWs had documented epilepsy, presenting clinically with partial or generalized epilepsy. It is notable that one-third of the patients with SSWs had chronic or static central nervous system (CNS) pathology, particularly congenital CNS anomalies. Though more than one mechanism may be involved in the pathogenesis of SSWs, this research indicates that the most compelling theory is a deeply seated cortical generator giving rise to this EEG pattern. The presence of SSWs should alert clinicians to the presence of partial or generalized epilepsy or an underlying chronic or static CNS pathology, in particular congenital CNS anomalies, underscoring the significance of brain magnetic resonance imaging in the work-up of this population. PMID- 27373056 TI - A Case Study of Gamma Waves in a Woman with Recent Psychotic Symptoms. AB - Reported here is the case of a 41-year-old female who developed paranoia and delusions. Physical examination, laboratory studies, and neuroimaging were unremarkable. She was diagnosed with schizophrenia and treated with risperidone, ultimately at a dose of 3 mg daily, with improvement. Her EEG showed bursts of 30 40 Hz gamma activity in the frontal regions, a finding sometimes noted on the resting EEGs of patients with schizophrenia. This report discusses gamma activity as well as other EEG abnormalities that may occur on the resting EEG of patients with schizophrenia. Additionally discussed is recent research suggesting that 35 45 Hz gamma activity associated with active information processing and cognition may be decreased in patients with schizophrenia compared to normal individuals. The role of gamma activity, both in the resting state and during cognitive activity, could be an area of importance for future research in schizophrenia and possibly other disorders. PMID- 27373057 TI - Anti-NMDAR Encephalitis. AB - Anti-N-methyl-D-aspartate receptor encephalitis is a newly described disease process. Patients are generally young females who present with psychiatric symptoms and progress to have seizures, abnormal movements, and. autonomic instability. Diagnosis is made based on serum and cerebrospinal fluid results, However, a characteristic EEG pattern described as extreme delta brush has been associated with this disorder making it especially relevant to neurodiagnostic technologists in practice today. Our case presentations follow two patients through the course of their illness and recovery. PMID- 27373058 TI - WAVEFORM WINDOW #36. "Shake, Rattle, and Roll": The Importance of Recognizing and Documenting Physiologic Artifacts during Routine, Continuous, or Ambulatory EEG. PMID- 27373059 TI - Summary of Auger-Related Entanglement Incidents Occurring Inside Agricultural Confined Spaces. AB - Entanglements in energized equipment, including augers found in agricultural workplaces, have historically been a significant cause of traumatic injury. Incidents involving augers located inside agricultural confined spaces (primarily grain storage structures and forage silos), although relatively rare events, are a widely recognized problem due to the relative severity of the resulting injuries and the complexities of victim extrication. However, this problem is neither well documented nor elucidated in the research literature, other than anecdotal observations relating to medical treatment of auger-related injuries and citations for non-compliance with federal and state workplace safety regulations. A review of nearly 1,650 cases documented in the Purdue Agricultural Confined Spaces Incident Database from 1964 to 2013 identified 167 incidents involving entanglement in an energized auger that occurred while the victim was working inside an agricultural confined space. These incidents primarily included in-floor unloading augers, sweep augers, stirring augers, and auger components found on silo unloaders. Cases involving portable tube augers used to handle grain outside grain storage structures were not included. Based on analysis of the data, approximately 98% of known victims were male, with the 21-45 age group reporting the largest number of incidents. Nearly one-third (32.3%) of incidents were fatal, and lower limb amputation was the most frequently reported injury type. (It is believed that non-fatal incidents are grossly under-reported in the data set due to a lack of comprehensive reporting requirements, especially for most farms, feedlots, and seed processing operations, which are generally exempt from compliance with OSHA machine guarding, confined-space, and grain-handling standards.) The type of auger identified most frequently as the agent of injury was the exposed in-floor auger (48), which frequently resulted in amputation of one or more lower limbs when the victim stepped into an unguarded opening or well in the floor of the confined space. The primary reason identified as to why workers were exposed to energized augers in the cases documented was to assist in the removal of residual or out-of-condition grain. The large number of cases involving augers on top-unloading silo unloaders (36) was not anticipated. Silo unloaders also accounted for the largest number of documented fatalities (15). This analysis is the first known attempt to provide a better understanding of the frequency, severity, and causative factors of these incidents. Those key causative factors were found to be: (1) lack of or inadequate guarding, (2) unintentional energizing of components due to a lack of lockout/tagout training and provisions, and (3) exposure of untrained or inexperienced workers to energized and unguarded components during procedures to remove residual grain or other agricultural crops from storage structures. It is hoped that the results and recommendations presented will raise awareness of the hazards related to using energized equipment in confined spaces as well as contribute to development of new evidenced-based educational resources, engineering safety standards, and workplace safety regulations. PMID- 27373060 TI - Object Detection for Agricultural and Construction Environments Using an Ultrasonic Sensor. AB - This study tested an ultrasonic sensor's ability to detect several objects commonly encountered in outdoor agricultural or construction environments: a water jug, a sheet of oriented strand board (OSB), a metalfence post, a human model, a wooden fence post, a Dracaena plant, a juniper plant, and a dog model. Tests were performed with each target object at distances from 0.01 to 3 m. Five tests were performed with each object at each location, and the sensor's ability to detect the object during each test was categorized as "undetected," "intermittent," "incorrect distance," or "good." Rigid objects that presented a larger surface area to the sensor, such as the water jug and OSB, were better detected than objects with a softer surface texture, which were occasionally not detected as the distance approached 3 m. Objects with extremely soft surface texture, such as the dog model, could be undetected at almost any distance from the sensor. The results of this testing should help designers offuture systems for outdoor environments, as the target objects tested can be found in nearly any agricultural or construction environment. PMID- 27373061 TI - Development and Validation of Written Exam Items for the Agricultural Hazardous Occupations Orders (AgHOs) Certification Training Program. AB - Research was conducted to develop and validate a pool of exam items that can be used to test the readiness of youth, ages 14-15 years, to be certified under the current federally mandated Agricultural Hazardous Occupations Orders (AgHOs). The AgHOs require training prior to employment in agricultural workplaces that the Secretary of Labor has determined are especially hazardous for youth within the prescribed age range. Under the current provisions of the AgHOs certification process, non-exempt youth seeking employment in agriculture are required to pass a written exam concentrating on safe work practices as partial satisfaction to receive certification of eligibility for employment to perform certain tasks. However, the regulations provide little guidance concerning the format of the exam, subject matter to be covered, degree of difficulty, or minimum passing score. As part of the USDA-sponsored Hazardous Occupations Safety Training in Agriculture (HOSTA) initiative, efforts have been made to develop consistent and evidence-based testing methods for disseminating the test protocols to instructors. The goal was to expand, enhance, and maintain the reliability of the exam item pool for the AgHOs certification process. Item development was based on the HOSTA-supported Gearing Up for Safety: Production Agriculture Safety Training for Youth curriculum. To ensure adequate item availability, the current item pool was expanded to include a minimum of two test items for each of the 157 cognitive based core competencies developed as part of the Gearing Up curriculum design process. Administering 70-item exams that were generated from the item pool to 568 youth, ages 13-18 years, provided evidence of item validity. The result was a pool of 367 validated exam items. PMID- 27373062 TI - Youth Personality Factors as Predictors of Risky All-Terrain Vehicle (ATV) Driving Behaviors. AB - Children and youth account for a disproportionately high number of all-terrain vehicle (ATV) related injuries and deaths. This study explored whether and how youth personality factors such as sensation seeking (including thrill seeking and behavioral intensity) and youth safety consciousness predict risky A TV riding behaviors. Survey information was collected from farm families in Georgia having youth who were active on farms. Data were analyzed from 104 youth between the ages 10 through 14 years who were active users ofATVs. Boys and girls had similar exposure to ATVs. Risky ATV riding behaviors were associated with age but not with gender. Boys and girls were equally likely to drive adult-sized ATVs, drive ATVs on public roads, drive ATVs fast, and carry extra passengers on single-seat ATVs. Boys had higher scores than girls on personality factors like thrill seeking and behavioral intensity. Hierarchical regression revealed that although there were multiple determinants of risky ATV riding behaviors of youth, thrill seeking appeared to be an important factor, which was moderated by safety consciousness. Youth who are low in thrill seeking and have a high level of safety consciousness reported less risky ATV riding behaviors. High thrill seekers were more likely to report indulging in risky ATV riding behaviors regardless of their level of safety consciousness. Our results suggest that personality traits (such as sensation seeking) of the target population should be considered when developing ATV safety interventions, as these traits will likely influence an intervention's level of success. Low thrill seekers would be prime candidates for safety training, as an increase in their safety consciousness may be more likely to result in decreased risky riding behaviors. High thrill seekers may be less amenable to training and will more likely require interventions external to the individual, including legislation, improved ATV safety design, use of crush protection devices, and safe riding rules monitored and strictly enforced by parents. PMID- 27373063 TI - Approaching Safety through Quality: Factors Influencing College Student Perceptions. AB - Quality management practices have been identified by previous literature as a factor that could potentially reduce the level of safety incidents and hazards in agricultural work environments. The present study used multivariate analysis to examine the effect of independent variables such as quality and safety awareness, work experience, safety and quality management experience, and the perceived importance of safety and quality on the role of quality management practices as a mitigating factor for safety hazards and incidents in agriculture. Variables were measured on a five-point scale using a survey questionnaire. Data were collected from approximately 900 undergraduates enrolled in the College of Agriculture and Life Sciences at a large land grant university in the U.S. The level of student work experience and student perceptions of the importance of quality explained a significant amount of the variance in student views of quality management practices as a mitigating factor for safety hazards and incidents. The findings of this study provide further evidence for using quality management practices as a basis for safety interventions targeted at the agricultural workforce. PMID- 27373064 TI - [Analysis of proposals received and funded in discipline of microbiology of the National Natural Science Foundation of China from 2011 to 2015]. AB - Based on a wrap-up of the research proposals received and awards made during 2011 through 2015 in the discipline of microbiology of the Department of Life Sciences, National Natural Science Foundation of China, this article presents a statistic analysis of award recipient institutions and main research trends, and attempts a prospective prioritization of the funding areas from the points of encouraging interdisciplinary research, optimizing funding instruments and strengthening talent training, with a view to providing reference for scientists and researchers in the field of microbiology. PMID- 27373065 TI - [Classification and prevalence of plasmid-mediated quinolone resistance qnr genes in China--A review]. AB - Quinolone antibacterial drugs, developing from the treatment of urinary tract infection in early time and now from the treatment of intestinal infection and respiratory infection, have been widely used in clinical, animal husbandry and aquaculture. Bacteria gradually become resistant to them and resistance mechanism is more and more complicated. Quinolone resistance mechanism is mainly divided into chromosome mediated resistance and plasmid mediated resistance, the latter plays an important role in spreading of antibiotic resistance. In 1998, plasmid mediated quinolone resistance mechanism was reported for the first time, namely the qnr gene mediated fluoroquinolone resistance mechanism. qnr genes can spread rapidly in different bacteria, which causes the infection difficult to control, makes the nosocomial infection popular in a wide range. In addition, qnr genes are usually associated with beta-lactamase resistance gene. They exist in complex integron and integrate with the other varieties of resistance genes, which narrows the space of clinical medicine choose or drug combinations use to treat related bacterial infection and brings us a serious challenge. In this review, we provide a detailed overview for the historical discovery, classification, the resistance mechanisms of qnr genes, and the prevalence of those genes in China. PMID- 27373066 TI - [Research progress in biofilm formation and regulatory mechanism of Campylobacter jejuni]. AB - Biofilm of Campylobacter jejuni was formed by cross-linking its extracellular secretion, polysaccharides, various extracellular proteins, nucleic acids etc to enhance its survival in hostile environments, especially for detergents, antibiotics and disinfectants. This paper elaborated C. jejuni biofilm formation and regulation mechanisms in the surface properties of the media, temperatures, gas environment, the regulation of gene etc, also analysed and discussed a variety of biofilm removal practical applications. We hope it can provide a reference for studies on biofilm control of C. jejuni. PMID- 27373067 TI - [Advances in humans and animals opportunistic pathogens from environment infecting plants by crossing kingdoms]. AB - Some pathogenic microorganisms ubiquitous in the environment could cross kingdoms to infect diverse hosts. Several cross-kingdom human pathogens were summarized in this paper, including Serratia marcescens, Enterobacter cloacae and Pseudomonas aeuriginosa. They are ubiquitous in the nature and could cause plant diseases using the same or different infection strategies with which they infect humans and broaden host range. Among these bacteria, Klebsiella pneumoniae causes top rot disease of maize in the nature, revealing some plants in the environment could serve as a reservoir of various pathogens which might infect animals and probably humans when conditions are favorable, and even potentially harm food. Research on these cross-kingdom pathogens may play a very important role in the epidemiology of human, animal and plant diseases and be a hot topic in environment science. PMID- 27373068 TI - [Advances in new vaccines against human enterotoxigenic Escherichia coli--A review]. AB - Enterotoxigenic Escherichia coli (ETEC) is the most common cause of diarrhea, which is a second leading cause of death for the children under five years old from all over the world. The key factors of ETEC contain both colonization factors (CFs) and enterotoxins including heat-labile enterotoxin (LT) and heat stable enterotoxin (ST). CFs mediated the binding of bacteria to the host intestinal epithelial cells, whereas LT and ST stimulated the over-secretion of body fluids and electrolytes, resulting in the destruction of the host fluid balance and leading diarrhea. The vaccine against CFs and enterotoxins could stimulate the host immune response, blocking ETEC adhesion and neutralizing enterotoxins, which is effective in the prevention of ETEC diarrhea. For the moment, depending on the stimulated immune response against LT, a cholera vaccine called Dukoral has been approved for use in some countries for the short-term protection and prevention of travelers' diarrhea. ETEC candidate vaccines are still in progress, which is designed to provide a long and wide-spectrum protection for ETEC infections. This paper briefly summarizes the advanced findings and key problems of vaccine development, and discusses prospects for future research. PMID- 27373069 TI - [Genetic manipulation system and genomic library of Streptomyces luteosporeus NRRL 2401]. AB - OBJECTIVE: To clone the biosynthetic gene clusters for secondary metabolites, we developed the genetic modification system and constructed a genomic library of Streptomyces luteosporeus NRRL 2401. METHODS: The genetic modification system was developed by using conjugal transfer vectors pSET152, pPM927 and pJTU1278 which were transferred from Escherichia coli ET12567/pUZ8002 to S. luteosporeus. The genomic library of S. luteosporeus NRRL 2401 was constructed by the fosmid vector pCClFOS, with E. coli EP1300 -T1 as the host strain. A PCR-based method was then developed for screening the biosynthetic gene clusters of secondary metabolites in the constructed genomic library. RESULTS: Vectors pSET152, pPM927 and pJTU1278 were successfully transferred into S. luteosporeus for genetic modification, with pSET152 presenting the highest transformation efficiency. The constructed genomic library of S. luteosporeus NRRL 2401 contained 2880 clones with an average -35 kb inserted DNA fragment in each clone, indicating the 99.99% coverage of the genome in the library. In this genomic library, we detected 9 clones containing possible indolmycin biosynthesis genes by the PCR-based screening method. CONCLUSION: A stable, efficient genetic modification system and high-quality genomic library could be used for discovery of the biosynthetic gene clusters for secondary metabolites in S. luteosporeus NRRL 2401. PMID- 27373070 TI - [Virtual screening and antibacterial activity of lead compounds targeting to penicillin-binding protein 3 (PBP3) of Pseudomonas aeruginosa]. AB - OBJECTIVE: This study was carried out to obtain lead compounds targeting penicillin-binding protein 3 (PBP3) of Pseudomonas aeruginosa by virtual screening. METHODS: UCSF dock 6.5 was used for the virtual screening from a database containing 1.04 million small molecules. Hit compounds with simple structures were synthesized and then evaluated for their antibacterial activities. RESULTS: Grid score was used for the first round of screening, and 60000 small molecules whose scores lower than -30 kcal/mol were screened out from the database. These molecules were subjected to the second round of screening using amber score. Approximately 200 hit compounds with scores lower than -20 kcal/mol were analyzed and 4 of them were selected as lead compounds and then synthesized. The minimal inhibition concentrations (MICs) of the lead compounds were between 175-275 MUg/mL, which were lower than that of Sulfadiazine (500 MUg/mL) significantly. Meanwhile, these compounds were effective for both Gram negative and Gram-positive bacteria. CONCLUSION: The lead compounds had potential to become new antibacterial agents for conquering the drug resistance of P. aeruginosa. PMID- 27373071 TI - [Phylogenetic comparison between Spirulina and Arthrospira based on 16S rRNA and rpoC1 gene]. AB - OBJECTIVE: Based on 16S rRNA and rpoC1 gene sequences, the phylogenetic relationship between Spirulina and Arthrospira were studied and compared. METHODS: We amplified, sequenced and analyzed 16S rRNA and rpoC1 of 84 strains. Then the phylogenetic trees were constructed and compared. RESULTS: The conserved sites percentage, average G+C content and sequence identity of rpoC1 were 49.7%, 47.7%, 76%-100% respectively, significantly lower than 79.4%, 55.6% and 91%-100% of 16S rRNA, and the heterogeneity degree was higher. The trees generated with two different genes showed similar topologies and thus inferred consistent phylogenetic relationships. Eighty-four experimental strains were divided into 3 groups belonging to 2 genera: F-35 1, F-904-2, F-1070 and TJBC14 were Spirulina and the rest were Arthrospira. Although morphospecies and geographical species could not be distinguished based on 16S rRNA and rpoC1 gene sequences, the bootstrap value of rpoC1 (100%) was higher than that of 16S rRNA (99%). Moreover, clustering effect of rpoC1 for Spirulina and Arthrospirai was better than 16S rRNA. CONCLUSION: Spirulina and Arthrospira were different genera, rpoC1 gene has more advantage to distinguish the strains in the same genus than that of 16S rRNA gene. PMID- 27373072 TI - [Diversity and bioactivity of actinomycetes isolated from medicinal plant Taxus chinensis and rhizospheric soil]. AB - OBJECTIVE: In order to provide strains with high activity of anti-phytopathogenic fungi and antitumor activity, we studied the diversity and bioactivity of actinomycetes isolated from medicinal plant Taxus chinensis and rhizospheric soil. METHODS: Seven selective media were used to isolate actinomycetes. Experiments of anti-phytopathogenic fungi, cytotoxicity activity, and the 16S rRNA gene sequencing of them were carried out to evaluate the diversity and bioactivity. Strains with high activity were identified. RESULTS: A total of 277 actinomycetes were isolated, of which 111 strains were selected and assigned to 6 suborders, 7 families and 8 genera, in which Streptomyces can be divided into 10 groups. The bioactivity testing results indicated that: 30.9% isolates showed activity against at least one of the 12 phytopathogenic fungi; 44.1% strains and 33.3% strains showed cytotoxicity activity with inhibition rate above 40% against stomach cancer cell line SGC-7901 and lung cancer cell line NCI-H460 respectively. CONCLUSION: Actinomycetes isolated from Taxus chinensis and rhizospheric soil is of high diversity and a good source for the selection of bioactive compounds. Streptomyces KLBMP 2170 is an excellent resource with antifungal and cytotoxicity activity for further studies. PMID- 27373073 TI - [Bacterial community characterization of rearing water of marine recirculating aquaculture systems for yellow grouper (Epinephelus awoara)]. AB - OBJECTIVE: This study was aimed to reveal the bacterial community characteristics of rearing water of marine recirculating aquaculture system for yellow grouper (Epinephelus awoara), and compare the differences between bacterial community structure of healthy rearing water and sick rearing water in order to elucidate the relationship between bacterial community and fish disease. METHODS: The next generation sequencing method was used, and the bacterial community structure and alpha-diversity indices (species richness, species evenness and phylogenetic diversity) between the rearing water of healthy and diseased groups were studied and compared. In addition, the traditional cultivation method was used to isolate suspected pathogens from the niduses of diseased yellow groupers. RESULTS: There was no significant difference between the alpha-diversities of healthy and diseased rearing water bodies, however, the results of principal coordinates analysis (PCoA) and the sample clustering of heatmap showed that the bacterial communities of healthy and diseased rearing water bodies were quite different. Although phyla Proteobacteria, Verrucomicrobia and Bacteroidetes were all the predominant ones in both communities, their relative abundance varied greatly. In diseased community, the relative abundances of alpha-Proteobacteria (25.07%) and gamma-Protebacteria (22.74%) were similar, whereas the proportion of gamma Protebacteria (40.49%) was much higher than alpha-Proteobacteria (10.87%) in the healthy community. The differences of Verrucomicrobia and Bacteroidetes between the healthy and the diseased rearing water were also significant with relative abundances of 10.9% and 26.4%, and 20.9% and 12.3%, respectively. The significantly different families were Rhodobacteraceae and Rhodospirillaceae within class alpha-Proteobacteria; Alteromonadaceae and HTCC2188 within class gamma-Protebacteria; Verrucomicrobiaceae within Verrucomicrobia; Cryomorphaceae within Bacteroidetes. The healthy and the diseased communities owned specific core microbes themselves. Glaciecola, HTCC, Sediminicola and Prevotella were the core genera in healthy rearing water, and Vibrio, Rubritalea and Oleibacter in diseased rearing water. Twenty strains of Vibrio spp. and one of Acinetobacter haemolyticus were isolated from skin, liver and spleen of diseased yellow grouper. CONCLUSION: The shift of bacterial community structure and relative abundance of rearing water will help monitor the healthy status of recirculating aquaculture system. Our study provides theory and experimental basis to diagnosis and monitor of Vibrio disease for yellow grouper recirculating aquaculture system. PMID- 27373074 TI - [E75, R78 and D82 of Escherichia coli FtsZ are key residues for FtsZ cellular self-assembly and FtsZ-MreB interaction]. AB - OBJECTIVE: To explore effects of FtsZ mutants FtsZ(E75A), FtsZ(R78G) and FtsZ(D82A) on FtsZ self-assembly and interaction of FtsZ with MreB in Escherichia coli strains. METHODS) We constructed FtsZ and its mutant's plasmids by molecular clone and site-directed mutagenesis methods, and purified targeted proteins by affinity chromatography. QN6(ftsZ::yfp-cat), QN7(tsZ::yfp-cat), QN8(ftsZ(R78G)::yfp-cat) and QN9 (ftsZ(D82A):.:yfp-cat) strains were constructed by linear DNA homologous recombination. We observed cellular localization pattern of FtsZ and its mutants in E. coli by living cell imaging experiments, examined interaction of FtsZ/FtsZ*-FtsZ* and FtsZ/FtsZ*-MreB by Coimmunoprecipitation and bacteria two hybrid, and analyzed assembly characteristics of FtsZ mutants by Light scattering. RESULTS) The Yfp-labeled FtsZ(E75A), FtsZ(R78G) and FtsZ(D82A) mutant proteins failed to assemble into functional Z-ring structure and localize correctly in E. coli strains. Interaction of FtsZ with its mutants, or FtsZ* FtsZ* and FtsZ*-MreB interaction were weakened or completely disappeared. In addition, in vitro experiments show that E75A, R78G and D82A mutations decreased the polymerization efficiency of FtsZ monomer. CONCLUSION: FtsZ E75, R78 and D82 are critical amino acids in the assembly, function of FtsZ protein and FtsZ-MreB interaction in E. coli strains. PMID- 27373075 TI - [Isolation and characterization of a Streptococcus suis serotype 9 from a wild cat]. AB - OBJECTIVE: Streptococcus suis (S. suis) is an emerging zoonotic pathogenic bacterium capable of infecting piglets and human and with sporadic infections in a variety of mammalian species. The aim of this study is to investigate the prevalence of S. suis in wild cats. METHODS: We isolated an S. suis strain from a wild cat. We tested the serotype of the isolated strain by anti-serum agglutination and PCR. We determined the sequence type (ST) of the isolated strain by multilocus sequence typing tests (MLST). We constructed the 16S rRNA phylogenetic tree of the isolation and S. suis strains in NCBI database to demonstrated genetic relationship of different strains. We measured the antibiotic resistance of the isolated strain by triple disk diffusion method. We detected the virulence of the isolated strain by mice infection experiments. RESULTS: We isolated an S. suis strain m70 from a wild cat, which belongs to serotype 9. MLST showed that m70 fell into a new ST. The 16S rRNA phylogenetic tree of m70 and S. suis strains in NCBI database demonstrated that m70 was in a separate cluster. m70 was resistant to tetracycline, intermediate to erythromycin, and sensitive to ampicillin, corresponding to clinical S. suis isolates in China. The mortality of mice infected with 10(8) CFU of m70 was achieved 60%-80% (3/5-4/5). The mean LD50 of mice infected with m70 was 5.1 x 10(7) CFU, while the mean LD50 of virulent S. suis strain HA9801 was 3.9 x 10(7) CFU. There is no significant difference between the LD50 of the two strains (P < 0.05). CONCLUSION: We isolated an S. suis strain from a wild cat, which belongs to the prevalent serotype and was a virulent strain, indicating the potential of transmission of S. suis from wild cats to humans, especially some prevalent serotype strains. PMID- 27373076 TI - [Identifying immunogenic proteins of Erysipelothrix rhusiopathiae C43065 by MALDI TOF mass spectrometry and cloning their encoding genes]. AB - OBJECTIVE: To identify immunogenic proteins of Erysipelothrix rhusiopathiae C43065. METHODS: Antigens were extracted from E. rhusiopathiae C43065 by the alkaline extraction method. Proteins in the NaOH-extracted antigen were separated by SDS-PAGE and transferred to nitrocellulose membranes, and then Western blotting was performed with rabbit antiserum against the NaOH-extracted antigens. The immunogenic protein bands were identified by MALDI-TOF mass spectrometry. The genes encoding 5 major immunogenic proteins was amplified by PCR from the genomic DNA of E. rhusiopathiae C43065, and inserted into the pMD18-T vector and then sequenced. RESULTS: A total of 9 immunogenic surface proteins in the NaOH extracted antigen from E. rhusiopathiae C43065 were successfully identified by MALDI-TOF mass spectrometry. Four of the proteins were putative virulence associated proteins: enolase, ATP-binding cassette transporter, glyceraldehyde-3 phosphate dehydrogenase and fructose-bisphosphate aldolase class-II. The genes encoding the chaperone protein GroEL, enolase, ATP-binding cassette transporter, glyceraldehyde-3-phosphate dehydrogenase and fructose-bisphosphate aldolase class II were 1614, 1296, 1260, 1005 and 867 bp in length, and the nucleotide sequences homologies of the genes between the C43065 strain and the previously reported E. rhusiopathiae Fujisawa strain was more than 98%. CONCLUSION: Several putative virulence-associated proteins in the NaOH-extracted antigen of E. rhusiopathiae C43065 will be useful for elucidating the roles of these proteins in the pathogenesis of the organism. PMID- 27373077 TI - [Gene deletion and functional analysis of the heptyl glycosyltransferase (waaF) gene in Vibrio parahemolyticus O-antigen cluster]. AB - OBJECTIVE: To construct heptyl glycosyltransferase gene II (waaF) gene deletion mutant of Vibrio parahaemolyticus, and explore the function of the waaF gene in Vibrio parahaemolyticus. METHODS: The waaF gene deletion mutant was constructed by chitin-based transformation technology using clinical isolates, and then the growth rate, morphology and serotypes were identified. The different sources (O3, O5 and O10) waaF gene complementations were constructed through E. coli S17lambdapir strains conjugative transferring with Vibrio parahaemolyticus, and the function of the waaF gene was further verified by serotypes. RESULTS: The waaF gene deletion mutant strain was successfully constructed and it grew normally. The growth rate and morphology of mutant were similar with the wild type strains (WT), but the mutant could not occurred agglutination reaction with O antisera. The O3 and O5 sources waaF gene complementations occurred agglutination reaction with O antisera, but the O10 sources waaF gene complementations was not. CONCLUSION: The waaF gene was related with O-antigen synthesis and it was the key gene of O-antigen synthesis pathway in Vibrio parahaemolyticus. The function of different sources waaF gene were not the same. PMID- 27373078 TI - [Correlation between superior enzymatic properties of beta-mannanase AuMan5A/Af and its residue Asp(320)]. AB - OBJECTIVE: AuMan5A is a glycoside hydrolase (GH) family 5 beta-mannanase from Aspergillus usamii. To improve its enzymatic properties, we have previously constructed a mutant with loop substitution, AuMan5A/Af, by substituting a loop of seven residues (316KSPDGGN322) in its substrate binding groove with the corresponding region (PSPNDHF) of A. fumigatus GH family 5 beta-mannanase. To reveal the correlation between the superior enzymatic properties of AuMan5A/Af and its residue Asp320, site-directed mutagenesis was used to obtain a new mutant enzyme AuMan5A/Af(D320G). METHODS: Using megaprimer PCR method, we constructed a new mutant-encoding gene, Auman5A/Af(D320G) by mutating an Asp320 -encoding codon GAC of Auman5A/Af into a Gly320 -encoding GGT. Then, Auman5A/Af(D320G) was extracellularly expressed in Pichia pastoris GS115, and the enzymatic properties of the expressed product were analyzed. RESULTS: Analytical results indicated that the optimal and melting temperature of AuMan5A/Af(D320G) was 70.0 degrees C and 71.5 degrees C, repectively, higher than those of AuMan5A (T(opt) = 65.0 degrees C, T(m) = 64.5 degrees C) and lower than those of AuMan5A/Af (T(opt) = 75.0 degrees C, T(m) =76.6 degrees C); its half-life at 70.0 degrees C was 40 min, 10 min longer than that of AuMan5A but greatly shorter than 480 min of AuMan5A/Af. Besides, its specific activity was 2.7 fold and 0.3 fold that of AuMan5A and AuMan5A/Af, respectively, and its catalytic efficiency (k(cat)/K(m)) was 3.9 fold and 0.3 fold that of AuMan5A and AuMan5A/Af. CONCLUSION: The mutation of ASP320 into Gly320 greatly affected the temperature characteristics and catalytic activity of AuMan5A/Af, demonstrating that Asp320 plays an improtant role in temperature characteristics, specific activity and catalytic efficiency improving of AuMan5A after loop substitution. PMID- 27373079 TI - [Characterization of a malic enzyme isoform V from Mucor circinelloides]. AB - OBJECTIVE: We aimed at characterizing a malic enzyme isoform V from Mucor circinelloides. METHODS: me1 gene encoding malic enzyme isoform V was amplified and cloned into expression vector pET28a. High-purity recombinant protein BLME1 was obtained by affinity chromatography using. Ni-NTA column and characterized subsequently. RESULTS: The optimum conditions were pH at 8.0 and temperature at 33 degrees C. Under optimum conditions, BLME1 activity achieved 92.8 U/mg. The K(m) for L-malate and NADP+ were 0.74960 +/- 0.06120 mmol/L and 0.22070 +/- 0.01810 mmol/L, the V(max) for L-malate and NADP+ were 72.820 +/- 1.077 U/mg and 86.110 +/- 1.665 U/mg, respectively. In addition, ions played important roles in BLME1 activity; several ions such as Mn2+, Mg2+, Co2+, Ni2+ could activate BLME1, whereas Ca2+, Cu2+ could be used as inhibitors. Additionally, the metabolic intermediates such as oxaloacetic acid and alpha-ketoglutaric acid inhibited the activity of BLME1, whereas succinic acid activated it. CONCLUSION: A malic enzyme isoform V from Mucor circinelloides was characterized, providing the references for further studies on this enzyme. PMID- 27373080 TI - [Isolation and characterization of siphovirus phages infecting bovine Streptococcus agalactiae]. AB - OBJECTIVE: To isolate and identify Streptococcus agalactiae phages and screen candidate phages to control infection caused by bovine S. agalactiae. METHODS: We used two methods for isolation of S. agalactiae phages, namely (1) isolation of phages from milk and environmental samples, and (2) isolation of phages via induction of lysogens with Mitomycin C. Double-layer agar culture method was used to purify phages. Then the newly obtained phages, with S. agalactiae phage JX01 isolated from mastitis milk, were comparatively analyzed in the following aspects: morphology of phages by transmission electron microscopy, host range of phages to 55 S. agalactiae strains and other Streptococcus strains, phages DNA using EcoR I, Xba I, Pst I and Sal I, the optical multiplicity of infection, absorption curve and one step growth curve, and the stability of phages at different storage conditions. RESULTS: The comparative analysis of the 3 novel phages LYGO9, HZ04 and pA11 (induced from S. agalctiae bovine clinical isolate HAJL2011070601) with JX01 showed that the 4 phages were classified as the member of Siphovirdae family. EcoR I, Sal I, Xba I and Pst I separately digested the 4 phages DNA provided 4, 3, 3 and 2 profiles, respectively. This suggested that they were different strains. All the 4 phages specifically infected bovine S. agalactiae isolates. LYGO9, pA11, JX01 and HZ04 could lyse 12, 13, 20 and 23 of 42 tested bovine S. agalctiae isolates, respectively. This clearly indicated that these 4 phages are closely related. CONCLUSION: The 3 new phages which specifically lyse bovine S. agalactiae isolates are siphovirus phages. Phage LYGO9 was shown having a short latent period and a larger burst size. PMID- 27373081 TI - [Clinical characteristic and therapeutic strategy of eosinophilic chronic rhinosinusitis]. PMID- 27373082 TI - [Phenotypes of chronic rhinosinusitis with nasal polyps: the progresses in precision medicine]. PMID- 27373084 TI - [Problems and strategies on diagnosis and exclusion of non-allergic rhinitis]. PMID- 27373083 TI - [Chronic nasal sinus mucosa inflammation mechanism research and clinical diagnosis]. PMID- 27373085 TI - [Expression and clinical significance of Eotaxin-3 in chronic rhinosinusitis with and without nasal polyps]. AB - OBJECTIVE: To investigate the expression and clinical significance of Eotaxin-3 in chronic rhinosinusitis with and without nasal polyps. METHOD: The ethmoid inflammation mucosa of 15 cases diagnosed as chronic rhinosinusitis (sinusitis group), the nasal polyps in the middle meatus of 25 cases diagnosed as nasal polyps (nasal polyp group) and the ethmoid or uncinate process mucosa of 7 cases diagnosed as sinonasal non-inflamnatory diseases (control group), were collected as the research object. Eotaxin-3 expression was detected in the tissues by immunohistochemical SABC assay and the correlation between Eotaxin-3 and blood eosinophil counts was analyzed. RESULT: Eotaxin-3 were detected both in sinusitis group and nasal polyp group, and the expression level in sinusitis group and nasal polyp group were higher than that in control group. The difference was statistically significant (P < 0.05). The Eotaxin-3 expression in nasal polyps group was higher than that in sinusitis group, and the difference was statistically significant (P < 0.05). The expression of Eotaxin-3 in nasal polyps group and sinusitis group were both significantly positively correlated with the eosinophil counts in the blood (P < 0.05). CONCLUSION: Eotaxin-3 may be involved,in the pathogenesis of chronic rhinosinusitis with and without nasal polyps, and further research will help us to understand the pathophysiology of chronic rhinosinusitis with and without nasal polyps. PMID- 27373086 TI - [Staphylococcus aureus biofilm influences the expression of lysozyme, SLPI and gp340 in a human sinonasal explant model]. AB - OBJECTIVE: To investigate the influences of staphylococcus aureus in planktonic and biofilm forms on the expression of lysozyme, SLPI and gp340 in the human sinonasal explant model. METHOD: Mucosa samples from ethmoid sinus were collected from ten patients of cerebrospinal fluid leak and were cultured with and without S. aureus biofilms and planktonic cells. After the infection, the explant model was confirmed by CLSM, and the secretion of lysozyme, SLPI and gp340 was detected by enzyme-linked immunosorbent assay (ELISA) at 8, 16, and 24 h after S. aureus challenge. Expressions of lysozyme, SLPI and gp340 in mRNA and protein levels after 24 h S. aureus challenge were detected using RT-PCR, immunohistochemistry and Western bolt assay respectively. RESULT: The secretion of lysozyme, SLPI and gp340 in the explant model was observed with a trend to increase in a time dependent manner. At 8 and 16 h after S. aureus challenge, the secretion of lysozyme, SLPI and gp340 in biofilms group was significantly higher than these in planktonic cells group and control group (P<0. 05). S. aureus biofilms enhanced the mRNA expressions of lysozyme, SLPI and gp340 significantly compared with planktonic cells and controls, and the mRNA expressions in the explant model challenged by planktonic cells were significantly higher than controls (P < 0.05). Although the Western bolt assay showed no differences between the lysozyme expression in the planktonic cells group and control group (P > 0.05), the biofilms enhanced the expressions of lysozyme, SLPI and gp340 significantly compared with planktonic cells and controls (P < 0.05). CONCLUSION: S. aureus biofilm induced the expressions of lysozyme, SLPI and gp340 to a higher level than planktonic cells, indicating that S. aureus biofilm was an influencing factor on the innate immune system. PMID- 27373087 TI - [Clinical pilot study on the rhinitis due to laryngopharyngeal reflux]. AB - OBJECTIVE: To explore the relevance between nasal symptoms and laryngopharyngeal reflux disease in patients with allergic rhinitis. METHOD: Thirty patients of laryngopharyngeal reflux disease were diagnosed in ENT outpatient department in our hospital. All patients have symptoms of sneeze, nasal discharge as chief complaint and they responded no effect for other normal treatment for nasal sinusitis at least three months. Orally before meals, a dose of 5 mg Mosapride citrate each time, three times a day for 7 days. Orally before meals, a dose of 20 mg Esomeprazole each time, two times a. day for 2-3 months. Nasal spray, one spray of azelastine hydrochloride once, two times a day for 2 month. RESULT: Laryngopharyngeal reflux symptom scores at four time points (the first visit, post treatment 15 days, 45 days, 75 days) were analyzed by repeated measures analysis of variance. There is a significant difference in four time points. CONCLUSION: Laryngopharyngeal reflux disease has a strong association with allergic rhinitis. Patients who has allergic rhinitis nasal symptoms as chief complaint must be exclude, the laryngopharyngeal reflux disease first. PMID- 27373088 TI - [Long-term outcome of budesonide middle meatus treatment for chronic rhinosinusitis patients following endoscopic sinus surgery]. AB - OBJECTIVE: To investigate the long term clinical effect of budesonide treatment in middle meatus for chronic rhinosinusitis(CRS) following endoscopic sinus surgery (ESS). METHOD: A total number of 53 patients with CRS received ESS were divided into two groups according to budesonide treatment: budesonide-treated group with 21 cases (39.6%) and control group with 32 cases (60.4%). Gelatin sponges soaked with 1 ml budesonide suspension were put in middle meatus in budesonide-treated group, while only gelatin sponges were put in middle meatus in control group. Visual analogy score (VAS), sino-nasal outcome test-22 (SNOT-22) and Lund-Kennedy endoscopic scale were carried out before ESS and two years after ESS. RESULT: In budesonide-treated group, there were a statistical difference before and after ESS in the VAS, SNOT-20 and Lund-Kennedy score (P<. 05). In control group, difference was also significant in VAS, SNOT-20 and Lund-Kennedy score before and after ESS (P < 0.05). The VAS gap of post-operative and pre operative in two groups are significantly different (P<. 05). However, there was no significant difference in the SNOT-20 and Lund-Kennedy endoscopic scale gap before or after the operation between two groups. CONCLUSION: It is safe, convenient and practicable to perform budesonide treatment in middle meatus following ESS, which can significantly ease the post-operative discomfort of nose. PMID- 27373089 TI - [Individual nasal endoscopic surgery for non-sinusitis-related rhinogenous headache: our experience in 68 cases]. AB - OBJECTIVE: To investigate the role of anatomical abnormalities in non-sinusitis related rhinogenous headache and to evaluate effects of nasal endoscopic surgery for non-sinusitis-related rhinogenous headache. METHOD: Sixty-eight patients diagnosed as non-sinusitis-related rhinogenous headache were selected in this study. They were treated with nasal endoscopic surgery after failed long-term medical treatment. Data from this group were analyzed retrospectively. RESULT: Multiple anatomical abnormalities were noted by endoscopy and sinus computed tomographic scans in the 66 patients. These included nasal septum deviation in 46 cases (67.6%), middle turbinate gasfication in 20 cases (29.4%), protruding ethmoid bulla or uncinate processor in 10 cases (14.7%) and abnormal middle turbinate in 8 case (11.8%). Fifty-six (82.4%) patients showed significant improvement after surgery. CONCLUSION: Non-sinusitis-related rhinogenous headache can be significantly minimized with individual nasal endoscopic surgery, as long as a precise identification of the etiologic anatomical factor can be made. PMID- 27373090 TI - [Observe the origin of antrochoanal polyp and the comparison of the curative effect of antrochoanal polyp]. AB - OBJECTIVE: To explore the curative effect and origin of antrochoanal polyp (ACP) with various approaches. METHOD: Fifty-seven patients with ACP were included in the study. All the ACP patients were examined by preoperative endoscopy and computer tomographic (CT) scans. The patients were treated by various endoscopic approaches including endoscopic middle meatus antrostomy, inferior meatus antrostomy combined with endoscopic middle meatus antrostomy or endoscopic medial maxillectomy combined with endoscopic middle meatus antrostomy respectively. The relationship between polyp location in middle meatus and lesions in the antrum was explored during the surgery. Pathological examination was carried out and patients were regularly followed up after operation. RESULT: Fifty-seven ACP develops from antral cyst. In 22 cases of endoscopic middle meatus antrostomy, two patients relapsed. In 17 cases of inferior meatus antrostomy combined with endoscopic middle meatus antrostomy, one patients relapsed. In 18 cases of endoscopic medial maxillectomy combined with endoscopic middle meatus antrostomy, no one relapsed. CONCLUSION: Our data indicated that the ACP mainly originates in antral cyst, and capsule wall herniates to middle meatus through the antral ostium. ACP are common in unilateral, rare in both sides. The endoscopic approaches of middle meatus antrostomy and inferior meatus antrostomy combined with endoscopic middle meatus antrostomy might guarantee good prognosis. If the cyst is on the anterior wall of maxillary sinus, the approach of endoscopic medial maxillectomy can obtain a better vision and completely remove the lesions. PMID- 27373091 TI - [The regulatory effect of IL-35 on the balance of Treg/Th17 cells in allergic rhinitis patients]. AB - OBJECTIVE: To study the regulatory effect of IL-35 on the balance of Treg/Th17 cells in AR patients. METHOD: In this study, 30 cases were randomly selected from outpatients of otolaryngological department in the second hospital of Hebei Medical university who were diagnosed as AR. Another 20 healthy cases enrolled from physical examination branch of our hospital were control group. The expression level of IL-35 and IL-17 in peripheral blood were detected by using ELISA and defeced CD4+CD25+Foxp3+ T cell and CD4+IL-17+T cell expression level were identified via flow cytometry. RESULT: The expression level of IL-35 in AR group was obviously lower than that in control group, and the difference was a statistically significance (t = -8.145, P < 0.01). The expression level of IL-17 in AR group was obviously higher than that in control group, and the difference was a statistically significance (t = 14.969, P < 0.01). There was a remarkable negative correlation between the IL-35 and IL-17 expression in the serum of AR group (r = -0.773, P < 0.01). The percentage of CD4+CD25+Foxp3+ T cell in CD4+ T cell was significant lower in AR group than that in control group (t = -13.678, P < 0.01). The percentage of CD4+IL-17+ T cell in CD4+ T cell was much higher in AR group than that in control group (t = 5.632, P < 0.01). There was a remarkable negative correlation between the Treg and Th17 expression in the peripheral blood of AR group (r = -0.613, P < 0.01). There was a positive correlation between the expression of CD4+ CD25+Foxp3+ T cell and IL-35. There was a negative correlation between the IL-35 and Th17 in AR group (r = 0. -594, P < 0.01). CONCLUSION: The lower expression of IL-35 was related to the incidence of AR, and it was an important cytokines for that. The lower expression of IL-35 may inhibit the proliferation of Treg cells, lead to hyper function of Th17 cells, increase secretion of s IL-17 and result in unbalance of Treg/Th17 cells; these may be the important mechanism of the occurrence of AR, thus regulation of IL-35 may become a new target for the immunological therapy of AR. PMID- 27373092 TI - [The clinical significance and changes of serum tumor necrosis factor and plasma endothelium in patients with OSAHS associated Type 2 diabetes mellites]. AB - OBJECTIVE: To investigate the significance of tumor necrosis factor-alpha (TNF alpha) and plasma endothelium (ET) in pathophysiologic process of patients with obstructive sleep apnea hypopnea syndrome(OSAHS) with type 2 diabetes mellitus (T2DM). METHOD: All observed subjects were divided into 4 groups. A number of 80 patients with OSAHS, 65 cases of OSAHS with T2DM patients, 20 patients with T2DM, and 32 cases of healthy control group were observed in this study. The serum levels of TNF-alpha and ET were detected by double antibody sandwich ELISA, the content of TNF-alpha and ET were compared between OSAHS group and OSAHS + T2DM group. It were also compared before and after treatment of CPAP or surgery. RESULT: TNF-alpha level is higher in OSAHS+T2DM group than that in the OSAHS group, T2DM group and the control group (P < 0.05); TNF-alpha level in OSAHS group and the T2DM group are higher than that in the control group (P < 0.05), but there was no difference in TNF-alpha level between the OSAHS group and the T2DM group. There was also no difference in ET level of the four groups. There were significant differences of TNF-alpha before and after treatment of CPAP or surgery in OSAHS group and OSAHS+T2DM group (P < 0.05). But there was no significant differences of ET before and after treatment of CPAP or surgery in the OSAHS+T2DM group (P > 0.05). CONCLUSION: TNF-alpha may be involved in the development of OSAHS and T2DM, while ET may have little effect on the occurrence and development of OSAHS and T2DM. PMID- 27373093 TI - [The expression and role of MIF, NF-kappaB and IL-1beta in nasal polyps]. AB - OBJECTIVE: To investigate the expression of MIF, NF-kappaB p65 and IL-1beta in the tissue of nasal polyps and normal inferior turbinate, to analyze their relevance, and to explore their role in nasal polyps. METHOD: The infiltrating results of EOS and others inflammatory cells in 48 cases diagnosed as nasal polyps (nasal polyps group) were detected by HE staining, and the expression of MIF, NF-kappaB p65 and IL-1beta were investigated by immunohistochemistry. Twenty one patients who were performed septoplasty orthotics were included as the control group; the VAS and Lund-Kennedy score were used to evaluate the degree of nasal polyps in patients and the correlation analysis was conducted between the disease severity and the expression levels of this three factors. RESULT: (1) The infiltrating results of EOS and the expression level of MIF, NF-kappaB p65, IL 1beta in nasal polyps group are obviously higher than these in the control group (P < 0.05); Spearman correlation analysis shows that MIF, NF-kappab p65 and IL 1beta are positively correlated with each other (r = 0.74, 0.66, 0.60, P < 0.05); the nuclear activation rate of NF-kappaB p65 is positively correlated with MIF, IL-1beta (r = 0.67, 0.63, P < 0.05); the infiltration degree of EOS is positively correlated with MIF, IL-1beta (r = 0.49, 0.55, P < 0.05), but has no correlation with the NF-kappaB p65 and its nuclear activation rate. (2) The VAS grade of the nasal polyps group is 8.24 +/- 1.72 and the nasal endoscopic examination grade is 8.63 +/- 3.81. Spearman correlation analysis shows that the VAS grade is positively correlated with the level of MIF (r = 0.71, P < 0.05), but had no correlation with NF-kappaB p65, its nuclear activation rate and IL-1beta. The nasal endoscopic examination grade is positively correlated with MIF and the nuclear activation rate of NF-kappaB p65 (r = 0.79, 0.73, P < 0.05), but has no correlation with the level of NF-kappaB p65 and IL-1beta (P > 0.05). CONCLUSION: MIF, NF-kappaB p65 and IL-1beta may promote the development of the nasal polyps, and there may exist the IL-1beta--NF-kappaB--MIF approach in nasal polyps; MIF and NF-kappaB may participate in maintaining physiological function of inferior turbinate and have relations with the lightest sustained inflammation of inferior turbinate. The MIF and NF-kappaB p65 nuclear activation rate can be used as a standard of the nasal polyp severity and the judgement prognosis. PMID- 27373094 TI - [Effect and mechanism of IL-1beta/JNK transduction pathway on the nasal mucosa remodeling in allergic rhinitis rats]. AB - OBJECTIVE: To study the role of JNK (c-Jun N-terminal kinase) signal transduction pathway on the nasal mucosa remodeling in allergic rhinitis rats, to explore whether IL-1beta participates the nasal mucosa remodeling in allergic rhinitis by JNK signal transduction pathway. METHOD: Totally 60 male Wistar rats (weighing about 200-250 g)were randomly divided into A (AR group) and B group (control group). The rats in A group were sensitized for inducing AR by intraperitoneal injection ovalbumin and Al(OH)3. Ovalbumin was respectively dropped in each nasal cavity of every rat for 4,8,12 weeks(A4,A8,or A12 group) each had 10 rats. The rats in B group were sensitized by intraperitoneal injection saline. Saline was respectively dropped in each nasal cavity of every rat for 4,8, 12 weeks(B4, B8, or B12 group), and each had 10 rats. The concentration of IL-1beta in serum and nasal lavage fluid were tested by ELASA. The protein expressions of P-JNK and P-c Jun were detected by immunohistochemical technique. Linear correlation analysis showed the correlation between levels of IL-1beta in serum and P-JNK protein, levels of IL-1beta in nasal lavage fluid and P-JNK protein. RESULT: The concentrations of IL-1beta in serum and nasal lavage fluid of A group were all significantly higher than those of the corresponding B group (all P < 0.01). Compared with A4 group and A8 group, concentrations of IL-1beta in nasal lavage fluid of A12 group were significantly increased (all P < 0.01). However the levels of IL-1beta in serum were not significantly different among them (all P > 0.05). Mean absorbance values of P-JNK and P-c-Jun in A group were significantly higher than those in corresponding B group (all P < 0.01) and compared with A4 group and A8 group, those of A12 group were significantly increased (all P < 0.01). Strong positive correlation were found between P-JNK and concentration of IL-1beta in serum or nasal lavage fluid (r = 0.835 and r = 0.902, all P < 0.01). CONCLUSION: JNK signal transduction pathway plays important role in the nasal mucosa remodeling in allergic rhinitis rats. IL-1beta participates in AR nasal mucosa remodeling possibly partly through activating JNK signal transduction pathway. PMID- 27373095 TI - [Efficacy of sublingual immunotherapy in children with allergic rhinitis]. AB - OBJECTIVE: To evaluate the efficacy of sublingual immunotherapy with dermatophagoides farina drops on children with allergic rhinitis. METHOD: This was retrospective study analyzing the efficacy of dermatophaguides farinae drops SLIT in 110 patients (aged 4-14 years old) with house dust mites induced allergic rhinitis (without asthma). All the patients were divided into the SLIT group (n = 60) and drug group (n = 50). Patients in SLIT group received sublingual immunotherapy combined with symptomatic medication, and patients in drug group only received symptomatic medication. We recorded and evaluated the total nasal symptom scores (TNSS), total medication scores (TMS) and visual analogue scale (VAS) of the 2 groups at three time points, before the treatment, and the treatment for 1-year and 2-year. RESULT: After 1-year and 2-year treatment, compared with drug group, TMS, TNSS and VAS in SLIT group decreased significantly (P < 0.01). When compared with baseline, we got the similar result as compared with drug group. Besides, the TMS of drug group increased significantly after treatment (P < 0.01). And no significant difference was observed in TNSS and VAS. In addition, there was significant difference in the Proportion of patients withdrawing symptomatic medication in SLIT group and drug group (68.33%,16.00%, respectively; P < 0.01). There were 4 local adverse reactions occurred during the treatment and no serious adverse events occurred. CONCLUSION: Sublingual immunotherapy with Dermatophagoides farinae drops showed significant clinical efficacy in children with allergic rhinitis comparing with pharmacotherapy. PMID- 27373096 TI - [Clinical analysis of 249 cases of children with foreign bodies in the nasal cavity and paranasal sinus]. AB - OBJECTIVE: Insertion of a foreign body in the nasal cavity is a very common incident in children. It is easily diagnosed, but the type of foreign body varies and the extraction can sometimes be difficult with risk of complications. The present study reported nasal foreign bodies diagnosed in emergency in our ENT department, with an update on the state of knowledge. METHOD: A prospective study between Feb 2013 to Sept 2015 included patients admitted to the ENT emergency unit for nasal foreign body. Data comprised age, gender, circumstances of discovery, symptoms, type of foreign body, extraction method and complications. Many patients required anterior rhinoscope for the diagnosis and removal (179/249, 71. 9%), and 170 cases were directly removed and 9 cases were into alimentary canal; Most irregularly shaped objects were removed by a endoscope under general anesthesia (70/249, 28.1%), including button batteries (n= 65), nasal calculi (n = 2) and chopsticks (n = 3). RESULT: The main types of foreign body were vegetal forms (61.8%). The incident was discovered following nasal symptoms in 24.9% (n = 62). Extraction was easy by using forceps, micro-hooks or suction in 71.9% of qn:Nasal sinuses foreign body on prevention, detailed history and make the necessary inspection, can improve the correct diagnostic rate. PMID- 27373097 TI - [The clinical features and drug therapy of unilateral idiopathic vocal fold paralysis]. AB - OBJECTIVE: To investigate the clinical features and medication of unilateral idiopathic vocal fold paralysis. METHOD: Thirty-nine of medical treated patients with unilateral idiopathic vocal fold paralysis were retrospectively studied, and relevant literatures were reviewed. RESULT: After 4 to 19 days of medical therapy, 9 patients were cured, the vocal fold movement of 18 sufferers were improved, and 12 pantients were not healed. CONCLUSION: Unilateral idiopathic vocal fold paralysis is common, and the treatment efficacy of medicine is almost the same with others. Unilateral idiopathic vocal fold paralysis is a disease with spontaneous recovery, which should be followed up. PMID- 27373098 TI - [Application of straight bite cutting sinus forcep in infant supraglottoplasty]. PMID- 27373099 TI - [Clinical analysis of 12 cases of sinonasal schwannomas]. PMID- 27373100 TI - [Personalized surgical operation of nasal septum deviation with endoscope]. PMID- 27373101 TI - [The operation treatment analysis of middle advanced thyroid carcinoma]. PMID- 27373102 TI - [Clinical manifestations of HIV-positive patients in otolaryngology head and neck surgery disease]. PMID- 27373103 TI - [Nasal endoscope surgery of acinic cell carcinoma of salivary gland on nasal septum: a case report]. AB - A 67-year-old male patient was admitted because of "the right side nasal obstruction repeatedly for 4 years". He got nasal obstruction 4 years ago, especially for the right side nasal cavity, sometimes got blood in his nasal discharge, then the symptom relieved after accepting treatment in local hospital. During the 4 years, the symptom repeatedly occurrence. Three days before hospitalization, the CT examination indicated abnormal things in his nasal cavity and the bone of his nasal sinus had been destroyed. Some abnormal organism were sent to pathological examination, and the report indicated it is acinic cell carcinoma of salivary gland. During the nasal endoscope surgery, a red goiter was found in his nose with its surface crude and brittle. Then we cut the goiter by nasal endoscope, during the operation we find the bottom of the goiter is on the nasal septum. Two weeks after the operation, the patient received the radiation therapy. One year after the operation he doesn't get the abnormal symptom and the nasal MRI not found recidivation. PMID- 27373104 TI - [One cases of nasal synovial sarcoma]. AB - Synovial sarcoma is a rare tumour found in soft tissue; it is a mesenchymal spindle cell tumour that is not related to the synovial membrane. This tumour has a low incidence, and the most frequent place of occurrence is the lower extremities in young adults. Synovial sarcoma of the head and neck accounts for 3%-5% of sarcomas in this anatomical region. The tumor in the nasal cavity is less than 1%. The treatment of choice for synovial sarcoma of the head and neck is complete surgical excision of the tumour mass followed by adjuvant radiotherapy. PMID- 27373105 TI - [Nasal endoscopic surgery for osteoid osteoma of the periorbital skull base: a case report]. AB - Osteoid osteoma was first reported in 1935 by Jaffe. It is a kind of benign bone disease with the limitation of well-defined lesions. It is rarely seen in the periorbital region. The only symptom of the patient was unilateral proptosis of right. The result of MRI examination was cystic masses in the edge of the right orbit. The tumor was complete removed by the nasal endoscopic approach during the surgery. Pathology result was reported as osteoid osteoma. There was no significant complications of diplopia, visual acuity decreased, enophthalmos, cerebrospinal fluid leakage and others. PMID- 27373106 TI - [The review of transoral laser microsurgery in laryngeal cancer]. AB - Transoral laser microsurgery (TLM) has developed more than 40 years in the treatment of laryngeal cancer. TLM is especially important in the minimally invasive surgery of laryngeal carcinoma. Compared with the traditional open surgery, it is a major breakthrough, which has the significant advantages such as safety, effectiveness, low rate of local recurrence and high rate of larynx preservation. Not only can cure early laryngeal cancer, but also more and more the use of TLM in advanced supraglottic and glottic laryngeal cancer were reported. This article will review the characteristics, indications, superiority, surgical options and efficacy of the TLM in laryngeal carcinomas. PMID- 27373107 TI - PRESERVATIVES FROM THE EYE DROPS AND THE OCULAR SURFACE. AB - The use of preservatives in eye drops (eyewashes) has known glory at the beginning, but the side effects that they have on the ocular surface have led to a decrease of their popularity. Lachrymal film dysfunction, ocular hyperemia, dotted keratitis or toxic keratopathy were reported and analyzed in terms of pathophysiological mechanism of the role played by preservatives in ophthalmic drops (eyewashes). This article reviews the most common preservatives and the existing alternatives for the maintenance of the eye sterile drops. Keywords: preservatives, eye drops, ocular surface PMID- 27373108 TI - COGAN'S SYNDROME. AB - OBJECTIVES: The objective of our study was to review the current knowledge on Cogan's syndrome, including etiology, diagnosis and treatment. Systematic review methodology: Relevant publications on Cogan's syndrome from 1945 to 2014 were studied. CONCLUSIONS: Cogan's syndrome is a rare autoimmune vasculitis, with unknown pathogenesis. Infection was thought to have played a role in the pathogenesis of the disease, but now the autoimmunity hypothesis is considered more likely to be true. Cogan's syndrome is characterized by ocular and audiovestibular symptoms similar to those of Meniere's syndrome. Approximately 70% of the patients have systemic disease, of which vasculitis is considered the pathological mechanism. Corticosteroids are the first line of treatment; multiple immunosuppressive drugs were also used with varying degrees of success. The novelty in the treatment of the disease is tumor necrosis factor (TNF)-alpha blockers, but more studies are necessary to establish their efficacy. PMID- 27373109 TI - PLATEAU IRIS--DIAGNOSIS AND TREATMENT. AB - OBJECTIVES: The objective of our study was to review the current knowledge on the diagnosis and treatment options of plateau iris configuration and syndrome. SYSTEMATIC REVIEW METHODOLOGY: Relevant publications on plateau iris that were published until 2014. CONCLUSIONS: Plateau iris syndrome is a form of primary angle closure glaucoma caused by a large or anteriorly positioned ciliary body that leads to mechanical obstruction of trabecular meshwork. This condition is most often found in younger patients. Plateau iris has been considered an abnormal anatomic variant of the iris that can be diagnosed on ultrasound biomicroscopy or optical coherence tomography of anterior segment. Patients with plateau iris syndrome can be recognized by the lack of response in angle opening after iridotomy. The treatment of choice in these cases is argon laser peripheral iridoplasty. PMID- 27373110 TI - CORRELATIONS BETWEEN CONFOCAL MICROSCOPY AND HISTOLOGICAL ASPECTS OF NORMAL CORNEA. AB - The evaluation of the cornea through confocal microscopy is a revolutionary non invasive technique, which provides the ophthalmologist the histological and cytological in vivo images of the cornea, similar to those obtained through conventional histochemical methods. The current paper tries to prove and justify the similarity between the histological section model and the images obtained through confocal scanning, reflecting our experience with HRT II Cornea module. PMID- 27373111 TI - NEOVASCULAR SECONDARY GLAUCOMA, ETIOLOGY AND PATHOGENESIS. AB - RATIONALE: Neovascular secondary glaucoma is a condition characterized by increased intraocular pressure due to the neovascularization occurring at the iridocorneal angle and iris, the most common complication of end-stage ischemic retina. The early diagnosis and treatment of this disease are important, because the functional prognosis is reserved. OBJECTIVE: Knowing and understanding the etiology and pathogenesis of neovascular secondary glaucoma. METHODS AND RESULTS: Review of the angiogenesis theory to understand the etiology and pathogenesis of neovascular secondary glaucoma. VEGF is the most studied proangiogenic factor involved in the neovascular glaucoma pathogenesis. The 9 isoforms contain consensus signal sequences for extracellular secretion, all of them binding to a specific receptor subtype and stimulating tissue specific angiogenesis. VEGF and VEGF-m RNA levels are significantly increased in the ischemic retina. Diabetes mellitus (with diabetic retinopathy), central retinal vein thrombosis and repeated retinal detachments are diseases that cause neovascular glaucoma through ischemia. DISCUSSION: Correct evaluation of the iris neovascularization followed by a proper treatment is the most important in a case of secondary neovascular glaucoma. Repeated gonioscopy is indicated in cases with high risk of developing neovascular glaucoma. Close monitoring of a patient with high thromboembolic risk: valvular heart disease, open-heart surgery, other angioplasties. PMID- 27373112 TI - IRIS COLOUR CLASSIFICATION SCALES--THEN AND NOW. AB - Eye colour is one of the most obvious phenotypic traits of an individual. Since the first documented classification scale developed in 1843, there have been numerous attempts to classify the iris colour. In the past centuries, iris colour classification scales has had various colour categories and mostly relied on comparison of an individual's eye with painted glass eyes. Once photography techniques were refined, standard iris photographs replaced painted eyes, but this did not solve the problem of painted/ printed colour variability in time. Early clinical scales were easy to use, but lacked objectivity and were not standardised or statistically tested for reproducibility. The era of automated iris colour classification systems came with the technological development. Spectrophotometry, digital analysis of high-resolution iris images, hyper spectral analysis of the human real iris and the dedicated iris colour analysis software, all accomplished an objective, accurate iris colour classification, but are quite expensive and limited in use to research environment. Iris colour classification systems evolved continuously due to their use in a wide range of studies, especially in the fields of anthropology, epidemiology and genetics. Despite the wide range of the existing scales, up until present there has been no generally accepted iris colour classification scale. PMID- 27373113 TI - CORRELATIONS BETWEEN OPHTHALMOLOGY AND ORTHOPEDICS. AB - Although orthopedics and ophthalmology seem to be two different medical specialties, numerous studies that have been conducted in the past 35 years have shown a tight connection between several ocular pathologies and an increased risk of hip fractures due to falling. This article aims to review the ocular pathologies that have been proven to be associated with an increased risk of falling, to integrate the results of several studies showing a direct relationship between ocular pathologies and an increased risk of falling and finally to suggest ways in which the incidence of traumatic orthopedic injuries can be reduced by applying ophthalmologic principles. PMID- 27373114 TI - THE ADVANTAGES OF FEMTOSECOND LASER-ASSISTED CATARACT SURGERY. AB - PURPOSE: To present the advantages of performing femtosecond laser-assisted (Alcon-LenSx Inc.) cataract surgery. METHODS: Cataract surgery was performed with the LenSx femtosecond laser (Alcon-LenSx Inc.) in 50 eyes of 50 patients. The laser was programmed to perform a 4,9-4,5 mm capsulorhexis, a 2,3 mm main corneal incision, two 1,3 mm side-port incisions and either a hybrid-pattern or a cylinder-pattern fragmentation of the nucleus. The evaluated parameters were the capsulotomy, the corneal wounds and the nucleus fragmentation. Phacoemulsification of the nucleus and aspiration of the cortex were performed with the Alcon Centurion Vision System and monofocal, toric and multifocal IOLs were successfully implanted. RESULTS: A continuous, central, curvilinear capsulorhexis was performed in 48 cases, 96% (free-floating capsulotomy). In 2 cases, micro-adhesions were reported and detached with the Utrata forceps. Femtolaser capsulotomy resulted in a complete overlap of the anterior capsule over the IOL optics in all cases. Horizontal decentration was found in 2 cases, 4% and vertical decentration in 1 case, 2%. The main corneal incision was self sealing in 49 cases, 98%. Sutures were used in 1 case, 2%. The hybrid pattern of nucleus fragmentation was used in 42 cases, 84% and the cylindrical pattern in 8 cases, 16%. The fragmentation was incomplete in one case of white cataract and in one case of traumatic cataract. CONCLUSIONS: The main advantages of femtolaser cataract surgery are standardized corneal incisions, perfectly centered, round capsulorhexis, and lens nucleus fragmentation even in eyes with hard cataracts. The laser precision is due to the real time OCT software programs, which cover the whole anterior segment, up to the posterior lens capsule. PMID- 27373115 TI - FIGHTING MULTIPLE DRUG RESISTANCE: EFFECTS OF UV-ACTIVATED CHLORPROMAZINE ON RABBIT'S EYE PSEUDOTUMOURS. AB - INTRODUCTION: Multiple drug resistance requires a flexible approach to find medicines able to overcome it. One method could be the exposure of existing medicines to UV laser beams to generate active photoproducts against bacteria and/or malignant tumors. METHODS: The interaction of Chlorpromazine (CPZ) (irradiated with 266 nm pulsed laser beams) was studied at concentrations of 10 mg/ml and 20 mg/ ml in ultrapure water, with pseudotumors of rabbits eyes. RESULTS: The use of CPZ water solution exposed to 266 nm in the treatment of pseudotumor tissues produced on rabbit eyes showed that treatment results depend on initial (before irradiation) CPZ concentration and exposure time. At this stage, one could not specify which out of the generated photoproducts, individual or as a group, was/were efficient in pseudotumor cure but overall effects were observable. Application of CPZ irradiated solutions on rabbit eyes pseudotumors seemed to produce a faster recovery of tissues with respect to control, untreated eyes. CONCLUSIONS: Histologic findings in the treated tissues showed a good anti inflammatory response. The results obtained open perspectives to fight MDR and/or development of pseudotumoral processes with substances that were not initially made for this purpose (non-antibiotics, for instance). PMID- 27373116 TI - SCHOOL INTEGRATION FOR PATIENTS WITH AMBLYOPIA. AB - AIM: to identify the difficulties of social integration in patients with amblyopia, as well as the correlation between school results and the level of amblyopia. MATERIAL AND METHODS: An observational prospective study was performed in an interval of 2 years (2012-2014) for 43 amblyopic patients (24 females and 19 males), with age between 7 and 24 years. Patients were treated in "Sf. Spiridon" Hospital and Stereopsis Ophthalmological Clinic, Iasi. The patient or the assistant (parent, social assistant or grandparent) have filled in a questionnaire with 15 topics about school results and integration. Clinical parameters were registered for each patient: corrected visual acuity, type of optical correction, type of amblyopia, type of school attended, position in the desk, school results, behavior attitude, family involvement. All data was statistically analyzed. RESULTS: The cases were classified in three types of amblyopia: strabic amblyopia (11,63%), refractive amblyopia (67,44%) and deprivation amblyopia (20,93%). Depending on the value of visual acuity, one eye was with prosthetic, 11, 62% had moderate amblyopia and 32, 56% were cases with severe amblyopia. The majority of children were enrolled in normal schools (81,39%), 11,63% in special schools for children with low-vision and 2 patients were students (4,65%). Position of children in classroom was in 81,4% in first or second desk. Only 27,0% had very good results in school. Students had a social integration for study in faculties. CONCLUSIONS: A child with severe amblyopia has good or very good scholar results if the involvement of family and society is increased. There is no correlation between the position in the desk and the level of preparation. It is necessary an individualized educational attention for patients with amblyopia. PMID- 27373117 TI - ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY FOLLOWING INFLUENZA VACCINATION. AB - PURPOSE: To report a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE), following influenza vaccination. CASE REPORT: An 18-year old female patient developed a painless significant bilateral decrease of vision, moderate photophobia, metamorphopsia and intermittent headaches two weeks after having a seasonal anti-flu immunization. Clinical evaluation and ancillary testing pointed toward the diagnosis of APMPPE. The case evolved favorable after oral prednisone 0.5 mg/kg/day gradually decreased for over 4 weeks. A total recovery of visual function and no recurrences were noticed at 1, 3 and 5 years follow-up. CONCLUSIONS: Previous case reports already suggested a possible relationship between various immunizations and APMPPE onset. This case is the first one reported in our country. Epidemiological studies are required to link APMPPE occurrence and vaccination. PMID- 27373118 TI - VASCULAR ORBITAL TUMORS AT THE EXTREMES OF THE AGE SPECTRUM. AB - Vascular orbital lesions are rare and, due to the controversy surrounding their origin, frequently difficult to diagnose. Studies showed that approximately 10% of orbital space-occupying lesions are of vascular origin. The most frequent are capillary hemangioma in children and cavernous hemangioma, which, although congenital, reveals itself in adults. Two cases of vascular tumors in patients, at the extremes of the age spectrum are presented. PMID- 27373119 TI - POSTERIOR UVEITIS OR WET AGE-RELATED MACULAR DEGENERATION? CASE REPORT. AB - We present the case of a 61-year-old patient without previous ophthalmic or general history, who developed unilateral posterior pole granuloma and was diagnosed with posterior uveitis most likely due to a systemic Toxocara canis infection. Clinical examination and ancillary investigations showed elements that were also consistent with wet ARMD, but laboratory tests and successful use of oral anti-helminthic and corticosteroid therapy in decreasing the macular lesion and improving visual acuity, confirmed the diagnosis of posterior uveitis. PMID- 27373120 TI - CANALOPLASTY AFTER LASER TRABECULOPLASTY. AB - The paper presents a case of a pseudoexfoliative glaucoma previously treated with argon laser trabeculoplasty in a tertiary center, who was scheduled for canaloplasty in the Ophthalmology Department of the County Hospital Piatra Neamt, Romania. Although the status post laser trabeculoplasty is not among the best indications for canaloplasty, the article confirms the fact that this procedure can also be successfully performed in these cases. PMID- 27373121 TI - Metallic VS2 Monolayer Polytypes as Potential Sodium-Ion Battery Anode via ab Initio Random Structure Searching. AB - We systematically investigated the potential of single-layer VS2 polytypes as Na battery anode materials via density functional theory calculations. We found that sodiation tends to inhibit the 1H-to-1T structural phase transition, in contrast to lithiation-induced transition on monolayer MoS2. Thus, VS2 can have better structural stability in the cycles of charging and discharging. Diffussion of Na atom was found to be very fast on both polytypes, with very small diffusion barriers of 0.085 eV (1H) and 0.088 eV (1T). Ab initio random structure searching was performed in order to explore stable configurations of Na on VS2. Our search found that both the V top and the hexagonal center sites are preferred adsorption sites for Na, with the 1H phase showing a relatively stronger binding. Notably, our random structures search revealed that Na clusters can form as a stacked second layer at full Na concentration, which is not reported in earlier works wherein uniform, single-layer Na adsorption phases were assumed. With reasonably high specific energy capacity (232.91 and 116.45 mAh/g for 1H and 1T phases, respectively) and open-circuit voltage (1.30 and 1.42 V for 1H and 1T phases, respectively), VS2 is a promising alternative material for Na-ion battery anodes with great structural sturdiness. Finally, we have shown the capability of the ab initio random structure searching in the assessment of potential materials for energy storage applications. PMID- 27373122 TI - Cooperation of return-to-work professionals: the challenges of multi-actor work disability management. AB - PURPOSE: This article explores which concrete factors hinder or facilitate the cooperation of return-to-work (RTW) professionals in a complex system of multiple stakeholders. METHOD: The empirical material consists of in-depth interviews with 24 RTW professionals from various organizations involved in work disability management in Finland. The interviews were analyzed using thematic content analysis. RESULTS: The study revealed several kinds of challenges in the cooperation of the professionals. These were related to two partly interrelated themes: communication and distribution of responsibility. The most difficult problems were connected to the cooperation between public employment offices and other stakeholders. However, the study distinguished notable regional differences depending primarily on the scale of the local network. The main areas of improvement proposed by the interviewees were related to better networking of case managers and expansion of expertise. CONCLUSIONS: The article argues for the importance of systematic networking and stresses the role of public employment services in the multi-actor management of work disabilities. The article contributes to existing work disability case management models by suggesting the employment administration system as an important component in addition to health care, workplace and insurance systems. The study also highlights the need for expansion of expertise in the field. Implications for Rehabilitation Cooperation between RTW professionals in public employment offices and other organizations involved in work disability management was considered inadequate. In order to improve the cooperation of RTW professionals, the stakeholders need to create more systematic ways of communication and networking with professionals in other organizations. There is a need to expand the expertise in work disability management and rehabilitation, partly by increasing the role of other professionals than physicians. PMID- 27373123 TI - Preface. AB - This chapter briefly discusses the topics addressed in Volume 55 of the series Advances in Clinical Chemistry. PMID- 27373124 TI - Ni-Catalyzed Enantioselective C-Acylation of alpha-Substituted Lactams. AB - A new strategy for catalytic enantioselective C-acylation to generate alpha quaternary-substituted lactams is reported. Ni-catalyzed three-component coupling of lactam enolates, benzonitriles, and aryl halides produces beta-imino lactams that then afford beta-keto lactams by acid hydrolysis. Use of a readily available Mandyphos-type ligand and addition of LiBr enable the construction of quaternary stereocenters on alpha-substituted lactams to form beta-keto lactams in up to 94% ee. PMID- 27373125 TI - The immunomodulatory activity of secondary metabolites isolated from Streptomyces calvus on human peripheral blood mononuclear cells. AB - BACKGROUND: The natural products derived from micro-organisms are potential candidates for the discovery of novel drugs. Streptomyces bacteria are prolific sources of secondary metabolites with a wide variety of biological activities. Streptomyces calvus (S. calvus) is one strain of this genus and may be an appropriate candidate for isolating new compounds. In this study, the immunomodulatory effects of S. calvus secondary metabolites on the expression of various cytokine genes by human peripheral blood mononuclear cells (PBMCs) were evaluated. METHODS: A bacterial sample was inoculated in Mueller Hinton Broth and secondary metabolites were extracted. PBMCs were isolated from venous blood and were treated with S. calvus secondary metabolites for 48 h. The cell proliferation was assessed by Methyl tetrazolium bromide (MTT) assay and quantitative real-time polymerase chain reaction (qRT-PCR) assays to survey mRNA expressions of selected pro-inflammatory and inhibitory cytokine genes. RESULTS: Secondary metabolites augmented interleukin-2 and interferon-gamma gene expression in PBMCs at low doses and also reduced the levels of immunosuppressive cytokine interleukin-10. In addition, the proliferation of PBMCs substantially increased in response to metabolite treatment in a concentration-dependent manner (p < 0.001). CONCLUSION: This in vitro study revealed that the secondary metabolites from S. calvus can successfully stimulate human PBMCs. Therefore, these metabolites have the potential to serve as robust immunomodulators. PMID- 27373126 TI - Pilomatrixoma of the breast in a patient with type 1 myotonic dystrophy: successful surgical approach. AB - Malherbe?s calcifying epithelioma is an uncommon cutaneous tumour that originates from the matrix cells of hair follicle. It was initially described by Malherbe as a benign calcifying epithelioma. Several ultra-structural and electron microscopic studies later demonstrated its origin from matrix cells and the term pilomatrixoma was introduced. The treatment of this tumour remains mainly surgical. Malignant cases with post-surgical recurrences have been described in literature and recurrences have been related to an incomplete surgical treatment or tumour aggressiveness. We present the case of 31-year-old female patient with pilomatrixoma of the breast, which was very similar to fibroadenoma, in terms of size and other clinical features. We successfully treated this patient surgically, and the aesthetic results were good, despite the proximity of the tumour to the areola-nipple complex. Fifteen months later, the patient is doing well, free of any clinical local recurrence. PMID- 27373127 TI - 5-hydroxytryptamine and Lyme disease. Opportunity for a novel therapy to reduce the cerebellar tremor? AB - Lyme boreliosis is caused by the spirochete Borrelia burdorferi, which is transmitted by ticks. A 59 year-old woman developed pyrexia, strong headaches, ataxia, dysarthria and tremor of the limbs after a tick bite. She was unable to work and eat on her own. She was hospitalized three times and diagnosed with cerebellar intention tremor, cerebellar ataxia, dysarthria, bilateral horizontal gaze paralysis and a central lesion of the left facial nerve. There were no pyramidal, sensory or psychiatric disturbances. The brain MRI showed multifocal leucoencephalopathy with many hyperintense areas in both hemispheres, as well as in the left superior pedunculus cerebellaris. Diagnosis was confirmed by serologic examination. Treatment with cephtriaxone, doxycycline, methylprednisolone, cephixime and ciprofloxacine was administered without effect on the tremor, ataxia and horizontal gaze paralysis. Treatment was then administered with 5-hydroxytriptamine (5-HT) in increased doses. The result of the three-month treatment with 5-HT was a gradual diminution of the tremor and the ataxia and an increase in the ability to eat, walk and work independently. PMID- 27373128 TI - Isolated CMV infection causing perianal and sacral ulceration in a patient with aids. AB - Cytomegalovirus (CMV) is a DNA virus estimated to infect 70-90% of the world?s population, producing minimal symptoms in immunocompetent hosts. In the immunocompromised host, CMV infection can be potentially fatal, producing systemic or localized forms. We report the case of a 52-year-old female with acquired immunodeficiency virus (AIDS) who presented multiple sacral and perineal ulcers clinically and histopathologically consistent with CMV ulcerations. We discuss the patient?s clinical presentation and histologic findings to remind physicians to consider CMV as a cause for cutaneous and systemic infection in the immunocompromised host. PMID- 27373129 TI - Coexistent trichilemmoma and trichoblastoma without associated nevus sebaceus. AB - Trichilemmoma and trichoblastoma are benign adnexal neoplasms derived from the hair follicle unit. While trichilemmomas are closely associated with the epidermis, trichoblastomas are found within the dermis and subcutaneous tissue. Both tumors have been reported to arise within nevus sebaceus of Jadassohn (NSJ). We present a 42-year-old white male with a 5 mm crusted, erythematous papule on the right occipital scalp that had been present for years. A shave biopsy was performed and read as trichilemmoma involving the biopsy base. The patient returned for follow-up 2 months later with recurrence of a crusted papule, measuring 9 mm in greatest diameter at the site of the previous biopsy. The lesion was excised for complete histologic evaluation, diagnosed as trichilemmoma with verrucoid features and associated basaloid proliferation with adnexal differentiation, again involving the biopsy base. The lesion recurred 2 months later in the form of an 8 mm multilobulated pink nodule. It was again excised and diagnosed as trichoblastoma with overlying trichilemmoma. The significance of this finding is that coexistent lesions do not necessarily necessitate a preexisting nevus sebaceous. Rather, this finding supports the notion of a common stem cell capable of differentiating toward the various portions of the hair follicle unit and adnexal structures. The idea is that any portion of the skin adnexal structure may develop out of a pluripotential germ cell and develop into a tumor. PMID- 27373130 TI - Biofibre hair implant ? impact on the quality of life. AB - Body image refers to how we feel about our bodies. It does not refer to what we actually look like, but rather to our perceptions, opinions and ways of thinking about our appearance. How we feel about our appearance is part of our body image and self-image. The hair is a significant part of this image. The problem of alopecia affects both sexes and all ages with significant sequelae. Along with androgenetic alopecia, there are forms of alopecia of various origins: traumatic, surgical, pharmacological and others. Polyamide artificial hair implant (Biofibre(r)) is one of the current techniques used to treat this problem. PMID- 27373131 TI - Biofibre hair implant: what is new, what is true? AB - Ensuring the safety of hair implant fibers is essential. At the same time, good aesthetic quality and durability should also be considered in order to maintain expected result over the years. The main features required are biocompatibility, resistance to traction, absence of capillarity, resistance to physical-chemical stress, and low tissue trauma, in addition to good aesthetics. Biofibre(r) medical hair prosthetic fibers meet all the biocompatibility and safety requirements established by international standards for medical devices. They are available in 13 colors, with different lengths (15, 30 or 45 cm) and various shapes (straight, wavy, curly and afro). Biofibre(r) hair implants are indicated for diffuse hair loss or hair thinning in cases where an immediate aesthetic result is required, when patients request minor surgery without hospitalization, both for male and female patients, in combination with other hair restoration techniques to improve the final aesthetic result, to correct scars or scalp burns and in cases of poor donor areas. Biofibre(r) Hair Implant is in fact a minor surgery technique, performed under local anesthesia by either a manual implanter or an automatic machine which enables an immediate aesthetic result and the desired quantity of hair without pain or hospitalization. Clinical and histological studies have demonstrated that Biofibre(r) hair Implants are safe and well tolerated by patients and can be totally reversible if the need arises. This technique requires good after-care, periodical check-ups and yearly implant re-touches to maintain the best cosmetic result. PMID- 27373132 TI - Uncommon clinical presentation of Kimura?s disease as bilateral retroauricular masses in a young Malian male: successful surgical approach. AB - We present a case of a 27 year-old Malian male referred to our hospital for two large, painless retroauricolar masses that had appeared two years earlier. Bilateral cervical painless lymphadenopathy was present at physical examination, without any other systemic symptoms. His history was relevant for bilateral Kimura?s disease lesions resected 5 years earlier in the same locations. Lymphocytosis and a mild hypereosinophilia were found in routine blood tests, together with increased total IgE levels. After surgery, histology showed lymphoid infiltrates with reactive prominent germinal centres containing eosinophils, suggesting relapse of Kimura?s disease, in the context of nonencapsulated fibrous proliferation with discontinuous collagen fibers, consistent with keloid. Three months after removal of retroauricular masses, abnormal laboratory findings reverted to normal. To the best our knowledge, this is the first case in literature of bilateral keloid lesions developed after surgery for Kimura Disease and harbouring its histopathologic features. Clinicians should be aware of these unusual reactive phenomena and their possible simulators. PMID- 27373133 TI - Langerhans cell sarcoma: an unusual microscopic presentation. AB - A 70-year-old Caucasian male presented to our clinic for a pruritic eruption progressing over several months. He complained of fatigue with a 20-pound weight loss over the past year. On presentation, the patient had browny-yellow to violaceous, purpuric, macular and papular lesions on the legs, arms, lower abdomen and back. Initial biopsy showed an angiocentric infiltrate with a suggestion of intraluminal proliferation; CD31 and Fli-1 positivity suggested either reactive angioendotheliomatosis or an unusual intravascular histiocytosis. Further excisional biopsies demonstrated perivascular collections of cells with ample cytoplasm, prominent nuclear pleomorphism and mitotic activity. The nuclei demonstrated nuclear folding, grooves and indentations. The atypical cells were S100, CD1a and CD56 positive with immunohistochemistry. A diagnosis of Langerhans cell sarcoma (LCS) was made. LCS is a rare, aggressive malignancy that can involve multiple organs including the skin, lymph nodes, lung, bone marrow, spleen, heart, and brain. The skin and lymph nodes are commonly involved, and the cutaneous presentation varies greatly. Immunohistochemistry characteristically shows CD1a and S100 positivity. CD56 expression is uncommon and often portends a poor prognosis. There is no established treatment of LCS due to its rarity. Surgery, radiation, and chemotherapy have been used with varied outcomes. Our patient was treated with prednisone with improvement of cutaneous disease. He did not develop systemic involvement, but died 1.5 years later from complications associated with heart failure. Langerhans cell sarcoma should be considered when faced with an unusual angiocentric infiltrate in which initial immunohistochemical staining results may be misleading. PMID- 27373134 TI - Pulmonary and abdominal sarcoidosis, the great imitators on imaging? AB - Sarcoidosis is an insidious disorder that virtually affects every body organ. Lungs are the site most often affected (in up to 90% of patients) followed by intra thoracic more often than peripheral lymph nodes and other sites can be involved in different percentages. The evaluation of pulmonary sarcoidosis is best performed with high-resolution computed tomography (HRCT), as traditional chest X-ray has a low resolution and can be negative or give non-significant results. Disorders such as interstitial lung diseases (ILDs), tuberculosis, lung cancer and lymphangitis carcinomatosis can manifest with similar radiological findings that can deceive clinics and radiologists. The need of a clear distinction between these conditions is important not only for diagnostic purposes but also because treatment differs significantly in different conditions. However, conventional Ultrasound (US) can be negative if small lesions are present and false negative images can result if US is not followed by a contrast-imaging technique. Contrast enhanced computed tomography (CECT) and magnetic resonance imaging (CEMRI) are preferred to detect single or multiple masses, which appear hypodense and hypointense after contrast agent administration, respectively. We think that a correct algorithm should include a thorough clinical and radiological evaluation, a definite biopsy of affected tissues revealing classical non-caseating granulomas and a certain exclusion of conditions that can give similar clinical/histophatological patterns before considering the diagnosis of sarcoidosis. Only in these cases, a diagnosis of sarcoidosis can be sufficiently achieved before starting an appropriate treatment. PMID- 27373135 TI - Interstitial granulomatous dermatitis demonstrating small, discrete skin-colored papules. AB - We report the case of a 67-year-old female with a rare variant of interstitial granulomatous dermatitis showing multiple skin-colored papules. Clinically, numerous skin-colored or reddish papules were distributed on her back and posterior thighs with itchy scaly erythema on the upper back. After topical steroid application, skin-colored papules still remained after the disappearance of itchy scaly erythema. Histopathologically, perivascular and interstitial infiltration of lymphocytes and histiocytes with occasional multinucleated giant cells were observed in the superficial and mid reticular dermis, accompanied by mild mucin deposition. Interstitial granulomatous dermatitis is similar to interstitial granuloma annulare, but can be differentiated from it by lesser degrees of collagen degeneration with mucin deposition and frequent association with arthritis or rheumatic diseases. As previously reported, multiple asymptomatic skin-colored papules are considered a rare but distinct variant of interstitial granulomatous dermatitis. Although no apparent underlying disorder has developed in the presented case, careful follow-up needs to be continued. PMID- 27373136 TI - Medium-sized congenital melanocytic nevus of the forehead, glabella and temple ? surgical treatment and long-term follow-up. AB - Congenital melanocytic nevi can be stigmatising for the patient. Larger nevi bear an increased risk for melanoma development. Large congenital melanocytic nevi may be a symptom of neurocutaneous melanosis. We report on a 5-year-old boy with an extensive hair-bearing facial congenital melanocytic nevus, covering forehead, glabella and temple region associated with unilateral brow and blepharoptosis. The lesion was excised en bloc. The resulting defect had been closed by full thickness skin graft. Healing was unremarkable and long-term follow-up over 13 years demonstrated a satisfying esthetic and functional outcome. There was no evidence of melanoma development. Surgery is an option for disfiguring larger congenital melanocytic nevi as long as esthetics and function can be preserved. Long-term follow-up is recommended due to the increased risk of melanoma. PMID- 27373137 TI - Giant congenital melanocytic nevus in a bulgarian newborn. AB - Giant congenital melanocytic nevus (GCMN) is a rare disorder affecting 1 in 200,000?500,000 live births. Central nervous system defects such as spina bifida, meningocele, Dandy Walker malformation may accompany it and thus cause significant morbidity. Despite the related risk for malignant transformation, GCMNs may be associated with neurocutaneous melanosis, a rare syndrome in which a giant CMN or multiple smaller CMNs are accompanied by melanocytic deposition in the brain and the spinal cord. We present a case of a 5-day-old newborn with giant congenital melanocytic nevus on his back, as we discuss the diagnostic and treatment approach. PMID- 27373138 TI - Multifocal infantile progressive hemangiomatosis with ocular involvement: unique presentation in a Bulgarian newborn. AB - Vascular disorders are considered a common finding among infants and in general, hemangioma is the most common. Diffuse neonatal hemangiomatosis is a rare and frequently fatal variant of them. We describe a case of a 2-months-old infant with multiple cutaneous hemangiomatosis and ocular involvement. To the best of our knowledge, this is the first reported case. We focus on the different treatment modalities and current diagnostic approaches. PMID- 27373139 TI - Novel antidiabetic drugs and cardiovascular risk: Primum non nocere. AB - AIMS: Diabetes treatments aim at preventing undesirable metabolic effects of hyperglycemia and at preventing/reducing tissue damage, including cardiovascular (CV) events. For approval, novel diabetes drugs undergo early systematic investigation to assess CV safety. This review provides an updated analysis of the results of recent studies examining novel diabetes medications and CV outcomes. DATA SYNTHESIS: The new regulatory guidelines enforce adjudication of all CV events when testing novel diabetes drugs. Endpoints of CV mortality, myocardial infarction (MI), stroke and hospitalization for heart failure (HF) were included in the most recent clinical studies on novel antihyperglycemics. These are: the incretin mimetics glucagon-like peptide 1 (GLP-1) receptor agonists (GLP1-RA), the incretin enhancers dipeptidylpeptidase-4 (DPP-4) inhibitors (DPP4-I or gliptins), and the sodium-glucose cotransporter (SGLT2) inhibitors (SGLT2-I or gliflozins). The studies ELIXA and EXAMINE, testing lixisenatide and alogliptin, respectively, revealed non-inferiority versus placebo in terms of CV safety. The SAVOR-TIMI 53 results confirmed overall CV safety of saxagliptin, but raised a warning related to the increase in the risk of hospitalization for HF in the saxagliptin group. Recently, TECOS revealed a particularly favorable CV profile for sitagliptin while EMPA-REG showed a significant CV risk reduction in empagliflozin treated subjects. Ongoing studies will provide additional data on CV safety for other GLP1-RAs, DPP4-I and SGLT2-I. CONCLUSIONS: Results of safety outcome studies focused on CV events, including HF and mortality for CV causes, are not homogeneous. A critical analysis of these studies may help cardiologists and diabetes specialists to adapt their therapeutic choices to individual patients. PMID- 27373140 TI - Expression of kisspeptin/kiss1r system in developing hypothalamus of female rat and the possible effects on reproduction development and maintenance. AB - BACKGROUND: The kisspeptin/kiss1r system, expressed in the hypothalamic arcuate nucleus, has been proclaimed as one of the most powerful factors of the reproduction axis, according to recent researches in the reproductive field. The aim of this study was to ascertain the expression of kisspeptin, its receptor (kiss1r), and gonadotropin-releasing hormone (GnRH), and to explore the role on the development and maintenance of the reproductive function of developing female rats. METHODS: Expressions of the kisspeptin/kiss1r system were examined by immunohistochemistry and Real time Quantitative PCR (qRT-PCR). Expressions of estradiol (E2), luteinizing hormone, and follicle-stimulating hormone were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Expression of the kisspeptin/kiss1r system increased time dependently with aging, and their peak expression was demonstrated in the adult stage. GnRH showed a similar expression pattern to that of the kisspeptin/kiss1r system. ELISA results demonstrated that the E2, luteinizing hormone, and follicle-stimulating hormone secretion increased time dependently from infancy to prepuberty to puberty. However, E2 level decreased significantly in adult rats. Morphological changes of ovaries showed that primordial follicles, primary follicles, and growing follicle inhabited the dominant status in infancy, prepuberty, and puberty stages, respectively. CONCLUSION: GnRH neurons may play an intermediate role in the activation and maintenance of the reproductive function regulated by the kisspeptin/kiss1r system, which may also indirectly regulate the serum level of luteinizing hormone, follicle-stimulating hormone, and E2. PMID- 27373141 TI - Epidemiological trends for hospital admissions for acute rotavirus gastroenteritis in Belgium following the introduction of routine rotavirus vaccination and the subsequent switch from lyophilized to liquid formulation of RotarixTM. AB - This study describes epidemiological trends for acute rotavirus gastroenteritis (RVGE) in Belgium in children aged ?5 years during the period June 2007 to May 2014 after the introduction of routine rotavirus (RV) vaccination. This period encompassed the switch from lyophilized to the liquid formulation of RotarixTM (GlaxoSmithKline, Belgium) in August 2011. Uptake of RV vaccine remained consistently high throughout the study period with Rotarix the brand most often used. RV was present in 9% (1139/12 511) of hospitalized cases with acute gastroenteritis included in the study. Epidemiological trends for hospital admissions for RVGE remained consistent throughout the study period, with no evidence of any change associated with the switch from lyophilized to liquid formulation of Rotarix. This suggests both formulations perform similarly, with the liquid formulation not inferior regarding ability to reduce hospital admissions for acute RVGE in children aged ?5 years. A strong seasonal effect was observed with most RVGE occurring in the winter months but with some variability in intensity, with highest incidence found in those aged 6-24 months. The main observation was the decreased number of hospital admissions for RVGE in Belgium that occurred during winter 2013/2014. PMID- 27373142 TI - Mutations in ash1 and trx enhance P-element-dependent silencing in Drosophila melanogaster. AB - In Drosophila melanogaster, the mini-w(+) transgene in Pci is normally expressed throughout the adult eye; however, when other P or KP elements are present, a variegated-eye phenotype results, indicating random w(+) silencing during development called P-element-dependent silencing (PDS). Mutant Su(var)205 and Su(var)3-7 alleles act as haplo-suppressors/triplo-enhancers of this variegated phenotype, indicating that these heterochromatic modifiers act dose dependently in PDS. Previously, we recovered a spontaneous mutation of P{lacW}ci(Dplac) called P{lacW}ci(DplacE1) (E1) that variegated in the absence of P elements, presumably due to the insertion of an adjacent gypsy element. From a screen for genetic modifiers of E1 variegation, we describe here the isolation of five mutations in ash1 and three in trx that enhance the E1 variegated phenotype in a dose-dependent and cumulative manner. These mutant alleles enhance PDS at E1, and in E1/P{lacW}ci(Dplac), but suppress position effect variegation (PEV) at In(1)w(m)(4). This opposite action is consistent with a model where ASH1 and TRX mark transcriptionally active chromatin domains. If ASH1 or TRX function is lost or reduced, heterochromatin can spread into these domains creating a sink that diverts heterochromatic proteins from other variegating locations, which then may express a suppressed phenotype. PMID- 27373143 TI - Ospemifene May Not Treat Vulvar Atrophy: A Report of Two Cases. AB - INTRODUCTION: Ospemifene (Osphena, Shionogi Inc, Florham, NJ, USA) is an estrogen agonist and antagonist approved by the U.S. Federal Drug Administration for the treatment of "moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause." Although published, peer-reviewed, placebo-controlled studies have shown objective improvement in dyspareunia and in vaginal atrophy, there are no published data that have assessed changes in vulvar atrophy after the use of ospemifene. AIM: To present two cases of women with severe vulvar atrophy that showed no improvement with the use of ospemifene. METHODS: A review of two recent cases of a clinic specializing in the treatment of vulvovaginal disorders was performed. Case 1 was a 53-year-old menopausal woman who presented with non-provoked vulvar and vaginal discomfort and introital dyspareunia. She had used ospemifene 60 mg/d for 1.5 years without improvement in her symptoms before presentation. Case 2 was a 57-year-old menopausal woman who also presented with non-provoked vulvar rawness, burning, irritation, vaginal dryness, and introital dyspareunia. She had started ospemifene 60 mg/d 1 year before presentation and reported mild improvement in her vaginal dryness but no improvement in her vulvar irritation or introital dyspareunia. MAIN OUTCOME MEASURES: Change in vulvar atrophy and introital dyspareunia. CONCLUSION: These cases highlight the need to perform additional clinical trials that specifically assess the efficacy of ospemifene for changes in vulvar atrophy. PMID- 27373145 TI - Precision Imaging: more descriptive, predictive and integrative imaging. AB - Medical image analysis has grown into a matured field challenged by progress made across all medical imaging technologies and more recent breakthroughs in biological imaging. The cross-fertilisation between medical image analysis, biomedical imaging physics and technology, and domain knowledge from medicine and biology has spurred a truly interdisciplinary effort that stretched outside the original boundaries of the disciplines that gave birth to this field and created stimulating and enriching synergies. Consideration on how the field has evolved and the experience of the work carried out over the last 15 years in our centre, has led us to envision a future emphasis of medical imaging in Precision Imaging. Precision Imaging is not a new discipline but rather a distinct emphasis in medical imaging borne at the cross-roads between, and unifying the efforts behind mechanistic and phenomenological model-based imaging. It captures three main directions in the effort to deal with the information deluge in imaging sciences, and thus achieve wisdom from data, information, and knowledge. Precision Imaging is finally characterised by being descriptive, predictive and integrative about the imaged object. This paper provides a brief and personal perspective on how the field has evolved, summarises and formalises our vision of Precision Imaging for Precision Medicine, and highlights some connections with past research and current trends in the field. PMID- 27373144 TI - Common and unique genetic interactions of the poly(ADP-ribose) polymerases PARP1 and PARP2 with DNA double-strand break repair pathways. AB - In mammalian cells, chromatin poly(ADP-ribos)ylation (PARylation) at sites of DNA Double-Strand Breaks (DSBs) is mediated by two highly related enzymes, PARP1 and PARP2. However, enzyme-specific genetic interactions with other DSB repair factors remain largely undefined. In this context, it was previously shown that mice lacking PARP1 and H2AX, a histone variant that promotes DSB repair throughout the cell cycle, or the core nonhomologous end-joining (NHEJ) factor Ku80 are not viable, while mice lacking PARP1 and the noncore NHEJ factor DNA PKcs are severely growth retarded and markedly lymphoma-prone. Here, we have examined the requirement for PARP2 in these backgrounds. We find that, like PARP1, PARP2 is essential for viability in mice lacking H2AX. Moreover, treatment of H2AX-deficient primary fibroblasts or B lymphocytes with PARP inhibitors leads to activation of the G2/M checkpoint and accumulation of chromatid-type breaks in a lineage- and gene-dose dependent manner. In marked contrast to PARP1, loss of PARP2 does not result in additional phenotypes in growth, development or tumorigenesis in mice lacking either Ku80 or DNA-PKcs. Altogether these findings highlight specific nonoverlapping functions of PARP1 and PARP2 at H2AX-deficient chromatin during replicative phases of the cell cycle and uncover a unique requirement for PARP1 in NHEJ-deficient cells. PMID- 27373146 TI - Image-guided interventions and computer-integrated therapy: Quo vadis? AB - Significant efforts have been dedicated to minimizing invasiveness associated with surgical interventions, most of which have been possible thanks to the developments in medical imaging, surgical navigation, visualization and display technologies. Image-guided interventions have promised to dramatically change the way therapies are delivered to many organs. However, in spite of the development of many sophisticated technologies over the past two decades, other than some isolated examples of successful implementations, minimally invasive therapy is far from enjoying the wide acceptance once envisioned. This paper provides a large-scale overview of the state-of-the-art developments, identifies several barriers thought to have hampered the wider adoption of image-guided navigation, and suggests areas of research that may potentially advance the field. PMID- 27373147 TI - Dopamine D1 and D2 Receptors Make Dissociable Contributions to Dorsolateral Prefrontal Cortical Regulation of Rule-Guided Oculomotor Behavior. AB - Studies of neuromodulation of spatial short-term memory have shown that dopamine D1 receptor (D1R) stimulation in dorsolateral prefrontal cortex (DLPFC) dose dependently modulates memory activity, whereas D2 receptors (D2Rs) selectively modulate activity related to eye movements hypothesized to encode movement feedback. We examined localized stimulation of D1Rs and D2Rs on DLPFC neurons engaged in a task involving rule representation in memory to guide appropriate eye movements toward or away from a visual stimulus. We found dissociable effects of D1R and D2R on DLPFC physiology. D1R stimulation degrades memory activity for the task rule and increases stimulus-related selectivity. In contrast, D2R stimulation affects motor activity tuning only when eye movements are made to the stimulus. Only D1R stimulation degrades task performance and increases impulsive responding. Our results suggest that D1Rs regulate rule representation and impulse control, whereas D2Rs selectively modulate eye-movement-related dynamics and not rule representation in the DLPFC. PMID- 27373148 TI - 2.8-A Cryo-EM Structure of the Large Ribosomal Subunit from the Eukaryotic Parasite Leishmania. AB - Leishmania is a single-cell eukaryotic parasite of the Trypanosomatidae family, whose members cause an array of tropical diseases. The often fatal outcome of infections, lack of effective vaccines, limited selection of therapeutic drugs, and emerging resistant strains, underline the need to develop strategies to combat these pathogens. The Trypanosomatid ribosome has recently been highlighted as a promising therapeutic target due to structural features that are distinct from other eukaryotes. Here, we present the 2.8-A resolution structure of the Leishmania donovani large ribosomal subunit (LSU) derived from a cryo-EM map, further enabling the structural observation of eukaryotic rRNA modifications that play a significant role in ribosome assembly and function. The structure illustrates the unique fragmented nature of leishmanial LSU rRNA and highlights the irregular distribution of rRNA modifications in Leishmania, a characteristic with implications for anti-parasitic drug development. PMID- 27373149 TI - PCNA Retention on DNA into G2/M Phase Causes Genome Instability in Cells Lacking Elg1. AB - Loss of the genome maintenance factor Elg1 causes serious genome instability that leads to cancer, but the underlying mechanism is unknown. Elg1 forms the major subunit of a replication factor C-like complex, Elg1-RLC, which unloads the ring shaped polymerase clamp PCNA from DNA during replication. Here, we show that prolonged retention of PCNA on DNA into G2/M phase is the major cause of genome instability in elg1Delta yeast. Overexpression-induced accumulation of PCNA on DNA causes genome instability. Conversely, disassembly-prone PCNA mutants that relieve PCNA accumulation rescue the genome instability of elg1Delta cells. Covalent modifications to the retained PCNA make only a minor contribution to elg1Delta genome instability. By engineering cell-cycle-regulated ELG1 alleles, we show that abnormal accumulation of PCNA on DNA during S phase causes moderate genome instability and its retention through G2/M phase exacerbates genome instability. Our results reveal that PCNA unloading by Elg1-RLC is critical for genome maintenance. PMID- 27373150 TI - Impaired Recall of Positional Memory following Chemogenetic Disruption of Place Field Stability. AB - The neural network of the temporal lobe is thought to provide a cognitive map of our surroundings. Functional analysis of this network has been hampered by coarse tools that often result in collateral damage to other circuits. We developed a chemogenetic system to temporally control electrical input into the hippocampus. When entorhinal input to the perforant path was acutely silenced, hippocampal firing patterns became destabilized and underwent extensive remapping. We also found that spatial memory acquired prior to neural silencing was impaired by loss of input through the perforant path. Together, our experiments show that manipulation of entorhinal activity destabilizes spatial coding and disrupts spatial memory. Moreover, we introduce a chemogenetic model for non-invasive neuronal silencing that offers multiple advantages over existing strategies in this setting. PMID- 27373151 TI - NeuCode Proteomics Reveals Bap1 Regulation of Metabolism. AB - We introduce neutron-encoded (NeuCode) amino acid labeling of mice as a strategy for multiplexed proteomic analysis in vivo. Using NeuCode, we characterize an inducible knockout mouse model of Bap1, a tumor suppressor and deubiquitinase whose in vivo roles outside of cancer are not well established. NeuCode proteomics revealed altered metabolic pathways following Bap1 deletion, including profound elevation of cholesterol biosynthetic machinery coincident with reduced expression of gluconeogenic and lipid homeostasis proteins in liver. Bap1 loss increased pancreatitis biomarkers and reduced expression of mitochondrial proteins. These alterations accompany a metabolic remodeling with hypoglycemia, hypercholesterolemia, hepatic lipid loss, and acinar cell degeneration. Liver specific Bap1 null mice present with fully penetrant perinatal lethality, severe hypoglycemia, and hepatic lipid deficiency. This work reveals Bap1 as a metabolic regulator in liver and pancreas, and it establishes NeuCode as a reliable proteomic method for deciphering in vivo biology. PMID- 27373152 TI - Smc5/6 Mediated Sumoylation of the Sgs1-Top3-Rmi1 Complex Promotes Removal of Recombination Intermediates. AB - Timely removal of DNA recombination intermediates is critical for genome stability. The DNA helicase-topoisomerase complex, Sgs1-Top3-Rmi1 (STR), is the major pathway for processing these intermediates to generate conservative products. However, the mechanisms that promote STR-mediated functions remain to be defined. Here we show that Sgs1 binds to poly-SUMO chains and associates with the Smc5/6 SUMO E3 complex in yeast. Moreover, these interactions contribute to the sumoylation of Sgs1, Top3, and Rmi1 upon the generation of recombination structures. We show that reduced STR sumoylation leads to accumulation of recombination structures, and impaired growth in conditions when these structures arise frequently, highlighting the importance of STR sumoylation. Mechanistically, sumoylation promotes STR inter-subunit interactions and accumulation at DNA repair centers. These findings expand the roles of sumoylation and Smc5/6 in genome maintenance by demonstrating that they foster STR functions in the removal of recombination intermediates. PMID- 27373153 TI - Spinal Microgliosis Due to Resident Microglial Proliferation Is Required for Pain Hypersensitivity after Peripheral Nerve Injury. AB - Peripheral nerve injury causes neuropathic pain accompanied by remarkable microgliosis in the spinal cord dorsal horn. However, it is still debated whether infiltrated monocytes contribute to injury-induced expansion of the microglial population. Here, we found that spinal microgliosis predominantly results from local proliferation of resident microglia but not from infiltrating monocytes after spinal nerve transection (SNT) by using two genetic mouse models (CCR2(RFP/+):CX3CR1(GFP/+) and CX3CR1(creER/+):R26(tdTomato/+) mice) as well as specific staining of microglia and macrophages. Pharmacological inhibition of SNT induced microglial proliferation correlated with attenuated neuropathic pain hypersensitivities. Microglial proliferation is partially controlled by purinergic and fractalkine signaling, as CX3CR1(-/-) and P2Y12(-/-) mice show reduced spinal microglial proliferation and neuropathic pain. These results suggest that local microglial proliferation is the sole source of spinal microgliosis, which represents a potential therapeutic target for neuropathic pain management. PMID- 27373154 TI - Asymmetric Inheritance of Aggregated Proteins and Age Reset in Yeast Are Regulated by Vac17-Dependent Vacuolar Functions. AB - Age can be reset during mitosis in both yeast and stem cells to generate a young daughter cell from an aged and deteriorated one. This phenomenon requires asymmetry-generating genes (AGGs) that govern the asymmetrical inheritance of aggregated proteins. Using a genome-wide imaging screen to identify AGGs in Saccharomyces cerevisiae, we discovered a previously unknown role for endocytosis, vacuole fusion, and the myosin-dependent adaptor protein Vac17 in asymmetrical inheritance of misfolded proteins. Overproduction of Vac17 increases deposition of aggregates into cytoprotective vacuole-associated sites, counteracts age-related breakdown of endocytosis and vacuole integrity, and extends replicative lifespan. The link between damage asymmetry and vesicle trafficking can be explained by a direct interaction between aggregates and vesicles. We also show that the protein disaggregase Hsp104 interacts physically with endocytic vesicle-associated proteins, such as the dynamin-like protein, Vps1, which was also shown to be required for Vac17-dependent sequestration of protein aggregates. These data demonstrate that two physiognomies of aging reduced endocytosis and protein aggregation-are interconnected and regulated by Vac17. PMID- 27373155 TI - Protein Prenylation Constitutes an Endogenous Brake on Axonal Growth. AB - Suboptimal axonal regeneration contributes to the consequences of nervous system trauma and neurodegenerative disease, but the intrinsic mechanisms that regulate axon growth remain unclear. We screened 50,400 small molecules for their ability to promote axon outgrowth on inhibitory substrata. The most potent hits were the statins, which stimulated growth of all mouse- and human-patient-derived neurons tested, both in vitro and in vivo, as did combined inhibition of the protein prenylation enzymes farnesyltransferase (PFT) and geranylgeranyl transferase I (PGGT-1). Compensatory sprouting of motor axons may delay clinical onset of amyotrophic lateral sclerosis (ALS). Accordingly, elevated levels of PGGT1B, which would be predicted to reduce sprouting, were found in motor neurons of early- versus late-onset ALS patients postmortem. The mevalonate-prenylation pathway therefore constitutes an endogenous brake on axonal growth, and its inhibition provides a potential therapeutic approach to accelerate neuronal regeneration in humans. PMID- 27373156 TI - Transcription Factor NFIB Is a Driver of Small Cell Lung Cancer Progression in Mice and Marks Metastatic Disease in Patients. AB - Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor, and no effective treatment is available to date. Mouse models of SCLC based on the inactivation of Rb1 and Trp53 show frequent amplifications of the Nfib and Mycl genes. Here, we report that, although overexpression of either transcription factor accelerates tumor growth, NFIB specifically promotes metastatic spread. High NFIB levels are associated with expansive growth of a poorly differentiated and almost exclusively E-cadherin (CDH1)-negative invasive tumor cell population. Consistent with the mouse data, we find that NFIB is overexpressed in almost all tested human metastatic high-grade neuroendocrine lung tumors, warranting further assessment of NFIB as a tumor progression marker in a clinical setting. PMID- 27373157 TI - Identification and Targeting of Long-Term Tumor-Propagating Cells in Small Cell Lung Cancer. AB - Small cell lung cancer (SCLC) is a neuroendocrine lung cancer characterized by fast growth, early dissemination, and rapid resistance to chemotherapy. We identified a population of long-term tumor-propagating cells (TPCs) in a mouse model of SCLC. This population, marked by high levels of EpCAM and CD24, is also prevalent in human primary SCLC tumors. Murine SCLC TPCs are numerous and highly proliferative but not intrinsically chemoresistant, indicating that not all clinical features of SCLC are linked to TPCs. SCLC TPCs possess a distinct transcriptional profile compared to non-TPCs, including elevated MYC activity. Genetic and pharmacological inhibition of MYC in SCLC cells to non-TPC levels inhibits long-term propagation but not short-term growth. These studies identify a highly tumorigenic population of SCLC cells in mouse models, cell lines, and patient tumors and a means to target them in this most fatal form of lung cancer. PMID- 27373158 TI - The Zfhx3-Mediated Axis Regulates Sleep and Interval Timing in Mice. AB - An AT motif-dependent axis, modulated by the transcription factor Zfhx3, influences the circadian clock in mice. In particular, gain of function of Zfhx3 significantly shortens circadian rhythms and alters the transcriptional activity of an important class of neuropeptides that controls intercellular signaling in the suprachiasmatic nucleus (SCN) of the hypothalamus. The ZFHX3/AT axis revealed an important, largely cell-nonautonomous control of the circadian clock. Here, by studying the recently identified circadian mouse mutant Zfhx3(Sci/+), we identify significant effects on sleep homeostasis, a phenomenon that is outside the canonical circadian clock system and that is modulated by the activity of those neuropeptides at a circuit level. We show that the Zfhx3(Sci/+) mutation accelerates the circadian clock at both the hourly scale (i.e., advancing circadian rhythms) and the seconds-to-minutes scale (i.e., anticipating behavioral responses) in mice. The in vivo results are accompanied by a significant presence of sleep targets among protein-protein interactions of the Zfhx3(Sci/+)-dependent network. PMID- 27373159 TI - Structural Insights into Arl1-Mediated Targeting of the Arf-GEF BIG1 to the trans Golgi. AB - The GTPase Arf1 is the major regulator of vesicle traffic at both the cis- and trans-Golgi. Arf1 is activated at the cis-Golgi by the guanine nucleotide exchange factor (GEF) GBF1 and at the trans-Golgi by the related GEF BIG1 or its paralog, BIG2. The trans-Golgi-specific targeting of BIG1 and BIG2 depends on the Arf-like GTPase Arl1. We find that Arl1 binds to the dimerization and cyclophilin binding (DCB) domain in BIG1 and report a crystal structure of human Arl1 bound to this domain. Residues in the DCB domain that bind Arl1 are required for BIG1 to locate to the Golgi in vivo. DCB domain-binding residues in Arl1 have a distinct conformation from those in known Arl1-effector complexes, and this plasticity allows Arl1 to interact with different effectors of unrelated structure. The findings provide structural insight into how Arf1 GEFs, and hence active Arf1, achieve their correct subcellular distribution. PMID- 27373160 TI - Activation of CDK4 Triggers Development of Non-alcoholic Fatty Liver Disease. AB - The development of non-alcoholic fatty liver disease (NAFLD) is a multiple step process. Here, we show that activation of cdk4 triggers the development of NAFLD. We found that cdk4 protein levels are elevated in mouse models of NAFLD and in patients with fatty livers. This increase leads to C/EBPalpha phosphorylation on Ser193 and formation of C/EBPalpha-p300 complexes, resulting in hepatic steatosis, fibrosis, and hepatocellular carcinoma (HCC). The disruption of this pathway in cdk4-resistant C/EBPalpha-S193A mice dramatically reduces development of high-fat diet (HFD)-mediated NAFLD. In addition, inhibition of cdk4 by flavopiridol or PD-0332991 significantly reduces development of hepatic steatosis, the first step of NAFLD. Thus, this study reveals that activation of cdk4 triggers NAFLD and that inhibitors of cdk4 may be used for the prevention/treatment of NAFLD. PMID- 27373161 TI - Differences in Strength and Timing of the mtDNA Bottleneck between Zebrafish Germline and Non-germline Cells. AB - We studied the mtDNA bottleneck in zebrafish to elucidate size, timing, and variation in germline and non-germline cells. Mature zebrafish oocytes contain, on average, 19.0 * 10(6) mtDNA molecules with high variation between oocytes. During embryogenesis, the mtDNA copy number decreases to ~170 mtDNA molecules per primordial germ cell (PGC), a number similar to that in mammals, and to ~50 per non-PGC. These occur at the same developmental stage, implying considerable variation in mtDNA copy number in (non-)PGCs of the same female, dictated by variation in the mature oocyte. The presence of oocytes with low mtDNA numbers, if similar in humans, could explain how (de novo) mutations can reach high mutation loads within a single generation. High mtDNA copy numbers in mature oocytes are established by mtDNA replication during oocyte development. Bottleneck differences between germline and non-germline cells, due to early differentiation of PGCs, may account for different distribution patterns of familial mutations. PMID- 27373162 TI - A Role for Timp3 in Microbiota-Driven Hepatic Steatosis and Metabolic Dysfunction. AB - The effect of gut microbiota on obesity and insulin resistance is now recognized, but the underlying host-dependent mechanisms remain poorly undefined. We find that tissue inhibitor of metalloproteinase 3 knockout (Timp3(-/-)) mice fed a high-fat diet exhibit gut microbiota dysbiosis, an increase in branched chain and aromatic (BCAA) metabolites, liver steatosis, and an increase in circulating soluble IL-6 receptors (sIL6Rs). sIL6Rs can then activate inflammatory cells, such as CD11c(+) cells, which drive metabolic inflammation. Depleting the microbiota through antibiotic treatment significantly improves glucose tolerance, hepatic steatosis, and systemic inflammation, and neutralizing sIL6R signaling reduces inflammation, but only mildly impacts glucose tolerance. Collectively, our results suggest that gut microbiota is the primary driver of the observed metabolic dysfunction, which is mediated, in part, through IL-6 signaling. Our findings also identify an important role for Timp3 in mediating the effect of the microbiota in metabolic diseases. PMID- 27373163 TI - Nucleic Acid-Targeting Pathways Promote Inflammation in Obesity-Related Insulin Resistance. AB - Obesity-related inflammation of metabolic tissues, including visceral adipose tissue (VAT) and liver, are key factors in the development of insulin resistance (IR), though many of the contributing mechanisms remain unclear. We show that nucleic-acid-targeting pathways downstream of extracellular trap (ET) formation, unmethylated CpG DNA, or ribonucleic acids drive inflammation in IR. High-fat diet (HFD)-fed mice show increased release of ETs in VAT, decreased systemic clearance of ETs, and increased autoantibodies against conserved nuclear antigens. In HFD-fed mice, this excess of nucleic acids and related protein antigens worsens metabolic parameters through a number of mechanisms, including activation of VAT macrophages and expansion of plasmacytoid dendritic cells (pDCs) in the liver. Consistently, HFD-fed mice lacking critical responders of nucleic acid pathways, Toll-like receptors (TLR)7 and TLR9, show reduced metabolic inflammation and improved glucose homeostasis. Treatment of HFD-fed mice with inhibitors of ET formation or a TLR7/9 antagonist improves metabolic disease. These findings reveal a pathogenic role for nucleic acid targeting as a driver of metabolic inflammation in IR. PMID- 27373164 TI - Kataegis Expression Signature in Breast Cancer Is Associated with Late Onset, Better Prognosis, and Higher HER2 Levels. AB - Kataegis is a mutational process observed in ~55% of breast tumors that results in hypermutation in localized genomic regions. Using whole-genome sequence data of 97 tumors, we examined the distribution of kataegis loci, showing that these somatic mutations are over-represented on chromosomes 8, 17, and 22 and enriched in genic regions and active chromatin elements. We show that tumors harboring kataegis are associated with transcriptome-wide expression changes consistent with low invasive potential. We exploit the kataegis expression signature to predict kataegis status in 412 breast cancers with transcriptome but not whole genome sequence data and show that kataegis loci are enriched in high-grade, HER2(+) tumors in patients diagnosed with breast cancer at an older age and who have a later age at death. Our study demonstrates that kataegis loci are associated with important clinical features in breast cancer and may serve as a marker of good prognosis. PMID- 27373165 TI - NKp80 Defines a Critical Step during Human Natural Killer Cell Development. AB - Human natural killer (NK) cells develop in secondary lymphoid tissues (SLTs) through distinct stages. We identified two SLT lineage (Lin)(-)CD34(-)CD117(+/ )CD94(+)CD16(-) "stage 4" subsets according to expression of the C-type lectin like surface-activating receptor, NKp80: NKp80(-) (stage "4a") and NKp80(+) (stage "4b"). Whereas stage 4b cells expressed more of the transcription factors T-BET and EOMES, produced interferon-gamma, and were cytotoxic, stage 4a cells expressed more of the transcription factors RORgammat and AHR and produced interleukin-22, similar to SLT Lin(-)CD34(-)CD117(+)CD94(-)CD16(-) "stage 3" cells, whose phenotype overlaps with that of group 3 innate lymphoid cells (ILC3s). Co-culture with dendritic cells or transplantation into immunodeficient mice produced mature NK cells from stage 3 and stage 4a populations. These data identify NKp80 as a marker of NK cell maturity in SLTs and support a model of human NK cell development through a stage 4a intermediate with ILC3-associated features. PMID- 27373166 TI - Oxidative Homeostasis Regulates the Response to Reductive Endoplasmic Reticulum Stress through Translation Control. AB - Reductive stress leads to the loss of disulfide bond formation and induces the unfolded protein response of the endoplasmic reticulum (UPR(ER)), necessary to regain proteostasis in the compartment. Here we show that peroxide accumulation during reductive stress attenuates UPR(ER) amplitude by altering translation without any discernible effect on transcription. Through a comprehensive genetic screen in Saccharomyces cerevisiae, we identify modulators of reductive stress induced UPR(ER) and demonstrate that oxidative quality control (OQC) genes modulate this cellular response in the presence of chronic but not acute reductive stress. Using a combination of microarray and relative quantitative proteomics, we uncover a non-canonical translation attenuation mechanism that acts in a bipartite manner to selectively downregulate highly expressed proteins, decoupling the cell's transcriptional and translational response during reductive ER stress. Finally, we demonstrate that PERK, a canonical translation attenuator in higher eukaryotes, helps in bypassing a ROS-dependent, non-canonical mode of translation attenuation. PMID- 27373167 TI - Transmission of violet and blue light through conventional (layered) and bulk cured resin-based composites. AB - OBJECTIVES: This study measured the transmission of light in the 'violet' (350<=lambda<=425nm) and 'blue' (4250.98). Attenuation was greater for the 'violet' than for the 'blue' spectral regions. At the light tip, the violet light component represented 15.4% of the light output. After passing through 4-mm of RBC, the violet light represented only between 1.2 3.1% of the transmitted light depending on the RBC. Depending on RBC, approximately 100mW from the Bluephase G2 was transmitted through 0.1-mm of RBC in the 'violet' range, falling at most to 11mW after passing through 2-mm of RBC, and to only 2mW at 4-mm depth. CONCLUSIONS: Increasing RBC thickness results in an exponential decrease in light transmission. This attenuation is RBC-dependent with shorter wavelengths (violet) attenuated to a greater extent than longer wavelengths (blue). CLINICAL RELEVANCE: Despite the increased translucency of bulk curing RBCs, spectral radiant power shorter than 425nm from a curing light is unlikely to be effective at a depth of 4-mm or more. PMID- 27373168 TI - Comparative effects of amphetamine-like psychostimulants on rat hippocampal cell genesis at different developmental ages. AB - The aim of this study was to compare the effects of amphetamine-like psychostimulant drugs (i.e., MDMA, methamphetamine, D-amphetamine) on rat hippocampal cell genesis at different developmental ages (i.e., early adolescence vs. young adulthood) to determine if there were periods of vulnerability to drug induced brain changes. Although adolescence is a period of great vulnerability to the neurochemical effects of specific drugs of abuse, several reports suggest that adult rats are more susceptible than adolescents to the negative effects of these drugs. The main results suggest that the effects of these amphetamine drugs on cell genesis depend on the rat's developmental age, with the young adult period being more sensitive than the early adolescent one. In particular, MDMA and methamphetamine, but not D-amphetamine impaired hippocampal cell genesis (i.e., cell proliferation and cell survival) in young adult rats. These effects were dependent on the accumulative dose administered, as they were only observed with the highest dose tested (12 pulses of 5mg/kg over 4days: 60mg/kg total). The present results extend previous reports on adolescent insensitivity (i.e., better adaptation) to amphetamine-drugs and suggest for young adult rats certain degree of hippocampal damage that may mediate some of the addiction-like behaviors that depend on this brain region. Moreover, the present results, in line with previous data, suggest a possible role for the neuroplasticity marker BDNF and serotonin in regulating cell survival, as mBDNF protein regulation paralleled hippocampal cell survival and 5-HT2C-receptor content in young adult rats treated with these psychostimulant drugs. PMID- 27373169 TI - Pearls of Publishing: Advice for Increasing Your Acceptance Odds. AB - Pearls of wisdom can be a convenient and efficient strategy to improve performance. As Editors, we employ pearls to standardize the review and editorial process, and we offer our own pearls to you to help facilitate acceptance of submitted research manuscripts with the ultimate goal of strengthening scientific conclusions that can affect patient care, and ultimately, improve outcome. PMID- 27373170 TI - Regarding "Biomechanical and Computed Tomography Analysis of Adjustable Femoral Cortical Fixation Devices for Anterior Cruciate Ligament Reconstruction in a Cadaveric Human Knee Model". PMID- 27373171 TI - Authors' Reply. PMID- 27373172 TI - Regarding "Trends in Arthroscopic Procedures Performed During Orthopaedic Residency: An Analysis of Accreditation Council for Graduate Medical Education Case Log Data". PMID- 27373173 TI - Regarding "Does Gracilis Preservation Matter in Anterior Cruciate Ligament Reconstruction? A Systematic Review". PMID- 27373174 TI - Authors' Reply. PMID- 27373175 TI - Authors' Reply. PMID- 27373176 TI - Editorial Commentary: PRP: Platelet-Rich Plasma or Promising but Rarely Proven? AB - Cost-utility analysis using a Markov decision model finds that platelet-rich plasma (PRP) is not cost-effective in rotator cuff repair because of no added outcomes benefit or improvement in retear rate according to best current evidence (Level I to III studies). To achieve the willingness-to-pay threshold, PRP would need to reduce rotator cuff retear rates. The authors have opened dialogue for us to determine what is the value and what should be the cost for PRP when it comes to rotator cuff repair. PMID- 27373177 TI - Editorial Commentary: Just a Bit Outside: Elbow Ulnar Collateral Ligament Research Requires Critical Appraisal. AB - Elbow ulnar collateral ligament reconstruction (UCLR) in Major League Baseball players using either a docking technique or a modified Jobe technique (modified to avoid flexor-pronator detachment) is effective treatment in experienced hands. The study of UCLR in Major League Baseball players requires recording and reporting of the actual number of athletes treated by individual surgeons using different techniques, to determine practice patterns. Absent these data, and with poor response rate by the solicited physicians (41%), survey results may be misleading. In addition, although transient ulnar neuritis may occur during UCLR, permanent ulnar neuropathy is exceedingly rare. PMID- 27373178 TI - Editorial Commentary: Ischiofemoral Impingement: Is This the "New" Femoroacetabular Impingement? AB - In a single-surgeon study of more than 1,000 hip operations, 30 patients were identified with possible ischiofemoral impingement (IFI). Only 17 of these 30 (56.6%) patients ultimately were diagnosed as having IFI on the basis of magnetic resonance imaging, injections, arthroscopy, and the 2 clinical tests described. The IFI test and the long-stride walking test were both highly accurate for the purported diagnosis; however, the most accurate test that was not specifically prospectively studied was quadriceps muscle edema on magnetic resonance imaging, which was present only in otherwise confirmed cases of IFI and not seen with any other diagnosis. PMID- 27373179 TI - Editorial Commentary: Ligamentum Teres Tears and Femoroacetabular Impingement: Complex Coexistence of Impingement and Instability. AB - In a large Level IV case series of 2,213 hip arthroscopies with the diagnosis of femoroacetabular impingement, the intraoperative status of the ligamentum teres (LT) was recorded as normal in 11%, frayed and/or partially torn in 88%, and completely torn in 1.5% of hips. Although specific physical examination maneuvers for detecting LT tears were not available early in the study period, thus limiting a detailed assessment of such tests, the authors identified that female gender, a lower lateral center edge angle, a higher Tonnis angle, and capsular laxity were all associated with complete LT tears. This study further supports the complex coexistence of impingement and instability. PMID- 27373180 TI - Editorial Commentary: Shall We Just Get It All Done With? Simultaneous Versus Staged Bilateral Hip Arthroscopy. AB - Simultaneous bilateral hip arthroscopies have comparable patient-reported outcomes and little risk of complications when compared with staged bilateral hip arthroscopies in the treatment of femoroacetabular impingement. There will always be a selection bias, however: rehabilitation requiring 4-point gait will be more difficult, and some would consider that a simultaneous bilateral operation is more suited for the young, motivated, physically fit patient. PMID- 27373181 TI - Editorial Commentary: A Task May Be Done Quickly, but Not Necessarily Well. AB - The value of video gaming in relation to endoscopic surgical skills is explored in this article. Subjects who had more experience and performed better on 3 dimensional games also performed better on an arthroscopic simulator during tasks requiring manipulation of tools. Although the correlation is established, no data are presented to support causation. Video gaming holds promise in assisting the trainee attempting to develop components of endoscopic skill. Further investigation is required to demonstrate that improvements in performance can be expected to result. PMID- 27373182 TI - Editorial Commentary: Ankle Arthroscopy: Correct Portals and Distraction Are the Keys to Success. AB - Access to all areas of the ankle during arthroscopy is always problematic. The use of the correct portals and distraction increases access in both the supine and prone positions. Noninvasive distraction up to 30 pounds is safe and effective to perform arthroscopy in the supine position, and avoids the potential complications of pin distraction. PMID- 27373183 TI - Editorial Commentary: Improving Proficiency in Arthroscopic Knot Tying: Focus on Performance Over Appearance. AB - Arthroscopic knot tying is a challenging motor skill that is best learned at the benchtop, before surgery on patients. Recent studies suggest that these skills can be improved by direct assessment of knot biomechanics, providing the learner with immediate and objective feedback. To optimize proficiency at arthroscopic knot tying, we focus on performance over appearance. PMID- 27373184 TI - Editorial Commentary: The Search for the Cartilage "Holy Grail": Are We There Yet? AB - A study by Zhang et al. provided a Level IV systematic review of 23 studies (13 clinical and 10 basic science) that examined the current state of single-stage procedures for cartilage repair. The results of this review suggested that in the short-term (minimum 2-year follow-up), single-stage cell-based cartilage procedures significantly improve pain and function from the preoperative state and provide comparable defect fill and tissue quality as compared with their predecessor 2-stage procedures. The authors should be commended for summarizing the current state of single-stage cartilage repair techniques; however, further work must be done to find the cartilage restoration "holy grail." PMID- 27373185 TI - Does calling alcoholism an illness make a difference? The public image of alcoholism in Italy. AB - AIMS: Using data from a population survey in two communities in the region of Sardinia, Italy, we examined the association between illness definition and attribution of personal characteristics to people with alcoholism. METHODS: Quota samples, stratified by gender and age, were drawn from the general population (males: 48%; mean age 48+/-18; range: 15-90). A fully-structured interview was conducted face-to-face with 404 respondents. The assessment of the public view of 'alcoholics' was measured by their reactions to stimulus words rated on bipolar scales, and defined with adjectives with opposite meanings at each end. RESULTS: 322 participants (80%) rated the 'alcoholic' as 'ill'. The definition of the 'alcoholic' as being ill showed a statistically higher odd of stigma across all the dimensions of personal attributes. CONCLUSIONS: The expectation that people adopting the illness model would tend to blame less those afflicted for their condition and, consequently, stigmatize them less, was not confirmed. PMID- 27373186 TI - Differential sensitivity to learning from positive and negative outcomes in cocaine users. AB - BACKGROUND: Altered sensitivity to positive and negative outcomes may be linked to the maladaptive choices characteristic of substance use disorders. Few studies have determined the distinct roles that positive and negative outcomes play in stimulus-response learning in cocaine users. The purpose of the present study was to investigate sensitivity to learning from positive and negative outcomes on a probabilistic learning task in cocaine users employing human laboratory and crowdsourcing techniques. METHODS: Individuals who reported cocaine use were recruited for a laboratory study (Experiment 1) or an online study on Amazon.com's Mechanical Turk (mTurk) (Experiment 2). All participants completed a feedback-based probabilistic learning task in which images were classified into categories (A versus B). Positive and negative outcomes were provided in a probabilistic manner on separate trials. Proportion of optimal responses and response times were recorded. RESULTS: Active cocaine users were less sensitive to learning from positive relative to negative outcomes. These effects were consistent across image type and session in the laboratory sample. Similarly, reduced sensitivity to learning from positive outcomes was observed in cocaine users on mTurk. Control participants did not show suboptimal performance following positive or negative outcomes. CONCLUSIONS: This study extends the limited research on feedback-based learning in drug users by demonstrating reduced sensitivity to positive outcomes in cocaine users recruited in the human laboratory and online. Future studies on the clinical significance and mechanisms underlying this bias are needed to understand its relevance as a target for intervention development. PMID- 27373187 TI - Outcomes After Surgical Pulmonary Embolectomy for Acute Pulmonary Embolus: A Multi-Institutional Study. AB - BACKGROUND: Surgical pulmonary embolectomy (SPE) has been sparingly used for the successful treatment of massive and submassive pulmonary emboli. To date, all data regarding SPE have been limited to single-center experiences. The purpose of this study was to document short-term outcomes after SPE for acute pulmonary emboli (PE) at four high-volume institutions. METHODS: A retrospective review of multiple local Society of Thoracic Surgeons databases of adults undergoing SPE from 1998 to 2014 for acute PE was performed (n = 214). Demographic, operative, and outcomes data were collected and analyzed. Patients were summarily categorized as having either massive or submassive PEs based on the presence or absence of preoperative vasopressors. RESULTS: A total of 214 patients with acute PE were treated by SPE. The mean age was 56.0 +/- 14.5 years, and 92 (43.6%) patients were female. Of those, 176 (82.2%) PEs were submassive and 38 (17.8%) were massive. Fifteen (7.0%) patients underwent concomitant cardiac procedures, with 10 (4.7%) having simultaneous valvular interventions and 5 (2.4%) undergoing concomitant bypass grafting. Cardiopulmonary bypass (CPB) was used for all cases. Cardioplegic arrest was used for 80 (37.4%) patients. The median CPB and aortic cross clamp times were 71.5 (interquartile range [IQR], 47.0-109.5) and 46.0 (IQR, 26.0-74.5), respectively. Notably, only 25 (11.7%) patients died in the hospital. Mortality was highest among the 28 patients who experienced preoperative cardiac arrest (9, 32.1%) CONCLUSIONS: These data represent the first multicenter experience with SPE for acute pulmonary emboli. Surgical pulmonary embolectomy for acute massive and submassive PE is safe and can be performed with acceptable in-hospital outcomes; the procedure should be included in the multimodality treatment of life-threatening pulmonary emboli. PMID- 27373188 TI - Patient Safety: Disclosure of Medical Errors and Risk Mitigation. PMID- 27373189 TI - Early and Late Results of the Nuss Procedure in Surgical Treatment of Pectus Excavatum in Different Age Groups. AB - BACKGROUND: The aim of this study was a comparison of early and late results in surgical treatment of funnel chest using the Nuss method in patients in various age groups to find the optimal age to perform the corrective procedure. METHODS: Six hundred eighty patients operated on from June 2002 to October 2012 were included in the retrospective analysis. Patients were divided into 3 different age groups: group A = 156 patients from 7 to 14 years, group B = 328 patients aged 15 to 20 years, and group C = 196 patients older than 20 years of age. The mean follow-up was 33 months. RESULTS: Early non-life-threatening complications developed in 238 (35.0%) patients and frequency increased with age (group A, 24.3%; group B, 37.8%; group C, 38.8%; p = 0.0063). Good and very good corrective effects were achieved in 97.7 % of the entire patient population. Recurrence of the deformity was observed more often in younger patients (group A, 3.2 %) than in the other patients (group B, 1.2%; group C, 1.5%), although the difference between the studied groups was not significant (p = 0.3251). CONCLUSIONS: Good cosmetic results obtained with the use of the Nuss operation were not related to the age of the patients. The high incidence of minor complications in older patients seems to be an acceptable cost of a good cosmetic outcome and stable correction. Surgical morbidity is lowest in younger patients; however, the frequency of the recurrence of deformation is higher than in other groups. PMID- 27373190 TI - Ecosystem experiment reveals benefits of natural and simulated beaver dams to a threatened population of steelhead (Oncorhynchus mykiss). AB - Beaver have been referred to as ecosystem engineers because of the large impacts their dam building activities have on the landscape; however, the benefits they may provide to fluvial fish species has been debated. We conducted a watershed scale experiment to test how increasing beaver dam and colony persistence in a highly degraded incised stream affects the freshwater production of steelhead (Oncorhynchus mykiss). Following the installation of beaver dam analogs (BDAs), we observed significant increases in the density, survival, and production of juvenile steelhead without impacting upstream and downstream migrations. The steelhead response occurred as the quantity and complexity of their habitat increased. This study is the first large-scale experiment to quantify the benefits of beavers and BDAs to a fish population and its habitat. Beaver mediated restoration may be a viable and efficient strategy to recover ecosystem function of previously incised streams and to increase the production of imperiled fish populations. PMID- 27373191 TI - Corrigendum to "Determining treatment requirements for turbid river water to avoid clogging of aquifer storage and recovery wells in siliceous alluvium" [Water Res. 66 (2014) 99-110]. PMID- 27373192 TI - Comments to article "Accessibility to health care of diabetic patients with ST segment elevation acute coronary syndrome". PMID- 27373193 TI - Cleaning Puparia for Forensic Analysis. AB - We tested procedures for removing adipocere from insect samples to allow identification. An acceptable procedure was determined: (i) Samples were sorted in petri dishes with 75% alcohol to remove any larvae, adult insects, or other soft-bodied material. (ii) Samples of up to 24 puparia were placed in a vial with 15 mL of 95% acetone, capped, and vortexed for a total of 30-90 sec in 10- to 15 sec bursts. This step removed large masses of adipocere or soil from specimen. (iii) Specimens were removed from acetone and placed in a vial of 15 mL of 2% potassium hydroxide (KOH) and vortexed in 10- to 15-sec bursts until all puparia appeared clean (with our samples this required a total of 60-120 sec). (iv) Specimens were removed from the 2% KOH, placed in 75% ethanol, and examined microscopically. (v) Material was stored in 75% ethanol for identification and long-term preservation. PMID- 27373194 TI - Improving pancreas surgery over time: Performance factors related to transition of care and patient volume. AB - BACKGROUND: Pancreas surgery has evolved with better diagnostic imaging, changing indications, and improved patient selection. Outside high-volume tertiary centers, the documented effect of evolution in care and volumes are limited. Thus, we aimed to review indications and outcomes in pancreas surgery during the transition from community-based hospital to a university hospital. METHODS: All pancreatic surgeries performed between 1986 and 2012 within a well-defined Norwegian population were identified from the hospital's database. Indications and postoperative outcomes, including mortality, were investigated. RESULTS: Of the 219 included patients (54% males; median age, 64 years), 150 (69%) underwent pancreatoduodenectomy; 55 (25%), distal resection; and 5 (2%), enucleation. The annual number of operations increased during the study period (from <10/yr to >20/yr). Most patients (169; 77%) underwent surgery for suspected malignancy. The 30-day mortality decreased significantly over time among patients treated for pancreatic cancer (from 16.1% to 3.5%; p = 0.012). Over time, significant reductions in median hospitalization time (19 versus 12 days; p < 0.001), re operation rate (37.1% versus 8.4%; p < 0.001), and median ICU stay (3 versus 0 days; p < 0.001) were observed. CONCLUSION: The transition to university hospital and increase in volume has led to significant improvements in several performance metrics and reduced postoperative mortality. We believe improved perioperative management and focused, multidisciplinary care-bundles to be of importance. PMID- 27373195 TI - The GerdQ questionnaire and high resolution manometry support the hypothesis that proton pump inhibitor-responsive oesophageal eosinophilia is a GERD-related phenomenon. AB - BACKGROUND: Little is known about the relationship between proton pump inhibitor responsive oesophageal eosinophilia (PPI-REE), eosinophilic esophagitis (EoE) and gastro-oesophageal reflux disease (GERD). AIM: To compare high resolution manometry features and symptom profiles of patients with EoE, PPI-REE and GERD. METHODS: Consecutive patients diagnosed with EoE or PPI-REE according to international criteria (presence of at least one typical symptom of oesophageal dysfunction; at least 15 eosinophils per high-power field at mid/proximal oesophagus, persistence or resolution of eosinophils after an 8-week PPI trial), and a group of patients with proven GERD and oesophageal eosinophilia, prospectively completed the GerdQ questionnaire and underwent high resolution manometry. RESULTS: Thirty-five patients with EoE, 17 with PPI-REE and 27 with GERD were enrolled. When compared to GERD, both EoE and PPI-REE had higher rates of dysphagia (15% vs. 94% vs. 88%, P < 0.0001), patients with EoE reported heartburn and regurgitation less frequently (26% vs. 85%, and 17% vs. 74%, respectively; P < 0.001 for each and had lower GerdQ score [1 (0-6) vs. 8 (6-12), P < 0.001] than GERD patients. There was no significant difference comparing PPI REE and GERD patients. Patients with PPI-REE had a higher prevalence of erosive oesophagitis than patients with EoE (35% vs. 9%, P = 0.04), which was similar to that of GERD (48%, P = 0.54). Patients with EoE had a lower frequency of high resolution manometry features associated with GERD than patients with PPI-REE. There was no significant difference between PPI-REE and GERD patients. CONCLUSION: GERD, as assessed by GerdQ and high resolution manometry is common in patients with PPI-REE, which may share similar pathogenic mechanisms. PMID- 27373196 TI - Online obituaries are a reliable and valid source of mortality data. PMID- 27373197 TI - New insights into smoking cessation question the effectiveness of nicotine replacement therapy. PMID- 27373198 TI - The effectiveness of psychostimulants in ADHD treatment: Reversing parasympathetic promoting environmental influences? PMID- 27373199 TI - The role of PDGF-B/TGF-beta1/neprilysin network in regulating endothelial-to mesenchymal transition in pulmonary artery remodeling. AB - Endothelial-to-mesenchymal transition (EndoMT) has been recognized as a major reason for the pulmonary artery remodeling (PAR) in pulmonary artery hypertension (PAH). However, the molecular mechanisms and regulatory pathways involved in the EndoMT remain undefined. In the present study, we have confirmed that EndoMT was occurred in pulmonary arteries of rats induced by hypoxia and monocrotaline and in hypoxic pulmonary artery endothelial cells (PAECs). Moreover, hypoxia increased the expression of platelet-derived growth factor (PDGF) and transforming growth factor-beta1 (TGF-beta1) and decreased the expression of neprilysin (NEP), which contributed to the hypoxia-induced EndoMT of PAECs. Furthermore, a reciprocal regulation of PDGF-B and TGF-beta1 induced by decreasing NEP promoted the EndoMT of PAECs under hypoxia, which was a novel molecular mechanism to reveal the EndoMT participating in PAR. More importantly, imatinib, a PDGF receptor antagonist, relieved PAR and EndoMT in PAH rats. Thus, our results identify a novel mechanism to reveal the formation of EndoMT in PAH, and imply that imatinib may serve as a new therapeutic approach for treatment of the third cardiovascular disease. PMID- 27373200 TI - In situ characterization of protein aggregates in human tissues affected by light chain amyloidosis: a FTIR microspectroscopy study. AB - Light chain (AL) amyloidosis, caused by deposition of amyloidogenic immunoglobulin light chains (LCs), is the most common systemic form in industrialized countries. Still open questions, and premises for developing targeted therapies, concern the mechanisms of amyloid formation in vivo and the bases of organ targeting and dysfunction. Investigating amyloid material in its natural environment is crucial to obtain new insights on the molecular features of fibrillar deposits at individual level. To this aim, we used Fourier transform infrared (FTIR) microspectroscopy for studying in situ unfixed tissues (heart and subcutaneous abdominal fat) from patients affected by AL amyloidosis. We compared the infrared response of affected tissues with that of ex vivo and in vitro fibrils obtained from the pathogenic LC derived from one patient, as well as with that of non amyloid-affected tissues. We demonstrated that the IR marker band of intermolecular beta-sheets, typical of protein aggregates, can be detected in situ in LC amyloid-affected tissues, and that FTIR microspectroscopy allows exploring the inter- and intra-sample heterogeneity. We extended the infrared analysis to the characterization of other biomolecules embedded within the amyloid deposits, finding an IR pattern that discloses a possible role of lipids, collagen and glycosaminoglycans in amyloid deposition in vivo. PMID- 27373203 TI - Autophagy modulators regulate survival motor neuron protein stability in motoneurons. PMID- 27373204 TI - Subthalamic deep brain stimulation alters neuronal firing in canonical pain nuclei in a 6-hydroxydopamine lesioned rat model of Parkinson's disease. AB - INTRODUCTION: Chronic pain is one of the most common non-motor symptoms of Parkinson's disease (PD) affecting up to 85% of patients. Previous studies have established that reduced mechanical and thermal thresholds occur in both idiopathic PD patients and animal models of PD, suggesting that changes may occur in sensory processing circuits. Improvements in sensory thresholds are achieved using subthalamic nucleus (STN) deep brain stimulation (DBS), however the mechanism by which this occurs remains unresolved. MATERIALS AND METHODS: We examined unilateral medial forebrain bundle 6-hydroxydopamine (6OHDA) rat model of PD to determine whether STN DBS alters neuronal firing rates in brain areas involved in ascending and descending pain processing. Specifically, single unit in vivo recordings were conducted in the anterior cingulate cortex (ACC), the periaqueductal grey (PAG), and the ventral posteriolateral nucleus of the thalamus (VPL), before, during and after stimulation was applied to the STN at 50 or 150Hz. RESULTS: Sham and 6OHDA lesioned animals have similar neuronal firing activity in the VPL, ACC and PAG before stimulation was applied (p>0.05). In 6OHDA lesioned rats, both low frequency stimulation (LFS) (p<0.01) and high frequency stimulation (HFS) (p<0.05) attenuated firing frequency in the ACC. In shams, only LFS decreased firing frequency. A subset of neurons in the PAG was significantly attenuated in both sham and 6OHDA lesioned animals during HFS and LFS (p<0.05), while another subset of PAG neuronal activity significantly increased in 6OHDA lesioned rats during HFS (p<0.05). Finally, low or high frequency STN DBS did not alter neuronal firing frequencies in the VPL. CONCLUSIONS: Our results suggest that STN DBS alters neuronal firing in descending pain circuits. We hypothesize that STN DBS attenuates excitatory projections from the ACC to the PAG in 6OHDA lesioned rats. Following this, neurons in the PAG respond by either increasing (during HFS only) or decreasing (during both LFS and HFS), which may modulate descending facilitation or inhibition at the level of the spinal cord. Future work should address specific neuronal changes in the ACC and PAG that occur in a freely moving parkinsonian animal during a pain stimulus treated with STN DBS. PMID- 27373205 TI - Pseudophosphorylation of tau at S422 enhances SDS-stable dimer formation and impairs both anterograde and retrograde fast axonal transport. AB - In Alzheimer's disease (AD), tau undergoes numerous modifications, including increased phosphorylation at serine-422 (pS422). In the human brain, pS422 tau protein is found in prodromal AD, correlates well with cognitive decline and neuropil thread pathology, and appears associated with increased oligomer formation and exposure of the N-terminal phosphatase-activating domain (PAD). However, whether S422 phosphorylation contributes to toxic mechanisms associated with disease-related forms of tau remains unknown. Here, we report that S422 pseudophosphorylated tau (S422E) lengthens the nucleation phase of aggregation without altering the extent of aggregation or the types of aggregates formed. When compared to unmodified tau aggregates, the S422E modification significantly increased the amount of SDS-stable tau dimers, despite similar levels of immunoreactivity with an oligomer-selective antibody (TOC1) and another antibody that reports PAD exposure (TNT1). Vesicle motility assays in isolated squid axoplasm further revealed that S422E tau monomers inhibited anterograde, kinesin 1 dependent fast axonal transport (FAT). Unexpectedly, and unlike unmodified tau aggregates, which selectively inhibit anterograde FAT, aggregates composed of S422E tau were found to inhibit both anterograde and retrograde FAT. Highlighting the relevance of these findings to human disease, pS422 tau was found to colocalize with tau oligomers and with a fraction of tau showing increased PAD exposure in the human AD brain. This study identifies novel effects of pS422 on tau biochemical properties, including prolonged nucleation and enhanced dimer formation, which correlate with a distinct inhibitory effect on FAT. Taken together, these findings identify a novel mechanistic basis by which pS422 confers upon tau a toxic effect that may directly contribute to axonal dysfunction in AD and other tauopathies. PMID- 27373206 TI - Benefits of commercial weight-loss programs on blood pressure and lipids: a systematic review. AB - Our objective was to compare the effect of commercial weight-loss programs on blood pressure and lipids to control/education or counseling among individuals with overweight/obesity. We conducted a systematic review by searching MEDLINE and Cochrane Database of Systematic Reviews from inception to November 2014 and references identified by the programs. We included randomized, controlled trials >=12weeks in duration. Two reviewers extracted information on study design, interventions, and mean change in systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglycerides, and total cholesterol and assessed risk of bias. We included 27 trials. Participants' blood pressure and lipids were normal at baseline in most trials. At 12months, Weight Watchers showed little change in blood pressure or lipid outcomes as compared to control/education (2 trials). At 12months, Atkins' participants had higher HDL-c and lower triglycerides than counseling (4 trials). Other programs had inconsistent effects or lacked long-term studies. Risk of bias was high for most trials of all programs. In conclusion, limited data exist regarding most commercial weight-loss programs' long-term effects on blood pressure and lipids. Clinicians should be aware that Weight Watchers has limited data that demonstrate CVD risk factor benefits relative to control/education. Atkins may be a reasonable option for patients with dyslipidemia. Additional well-designed, long term trials are needed to confirm these conclusions and evaluate other commercial programs. PMID- 27373207 TI - Food reinforcement during infancy. AB - The motivation to eat, as operationalized by measuring how hard someone will work for food, is cross-sectionally and prospectively related to obesity. Persons high in food reinforcement consume more calories, and energy intake mediates the relationship between food reinforcement and obesity. Research has shown avid sucking for milk in early infancy predicts later adiposity, and the relationship between food reinforcement and excess body weight has been observed in infants as young as 9months of age. New methodological developments in studying food reinforcement in infants and young children provide the first opportunity to study the origin of food reinforcement. This review seeks to provide background on the measurement of food reinforcement, and to present, for the first time, prenatal and postnatal predictors of infant food reinforcement. Lastly, potential mechanisms for an increasing trajectory of food reinforcement throughout development are proposed. PMID- 27373208 TI - The emerging public discourse on state legalization of marijuana for recreational use in the US: Analysis of news media coverage, 2010-2014. AB - OBJECTIVES: US states have begun to legalize marijuana for recreational use. In the absence of clear scientific evidence regarding the likely public health consequences of legalization, it is important to understand how the risks and benefits of this policy are being discussed in the national dialogue. To assess the public discourse on recreational marijuana policy, we assessed the volume and content of US news media coverage of the topic. METHOD: We analyzed the content of a 20% random sample of news stories published/aired in high circulation/viewership print, television, and Internet news sources from 2010 to 2014 (N=610). RESULTS: News media coverage of recreational marijuana policy was heavily concentrated in news outlets from the four states (AK, CO, OR, WA) and DC that legalized marijuana for recreational use during the study period. Overall, 53% of news stories mentioned pro-legalization arguments and 47% mentioned anti legalization arguments. The most frequent pro-legalization arguments posited that legalization would reduce criminal justice involvement/costs (20% of news stories) and increase tax revenue (19%). Anti-legalization arguments centered on adverse public health consequences, such as detriments to youth health and well being (22%) and marijuana-impaired driving (6%). Some evidence-informed public health regulatory options, like marketing and packaging restrictions, were mentioned in 5% of news stories or fewer. CONCLUSION: As additional states continue to debate legalization of marijuana for recreational use, it is critical for the public health community to develop communication strategies that accurately convey the rapidly evolving research evidence regarding recreational marijuana policy. PMID- 27373209 TI - Brief interventions to prevent sexually transmitted infections suitable for in service use: A systematic review. AB - BACKGROUND: Sexually transmitted infections (STIs) are more common in young people and men who have sex with men (MSM) and effective in-service interventions are needed. METHODS: A systematic review of randomized controlled trials (RCTs) of waiting-room-delivered, self-delivered and brief healthcare-provider-delivered interventions designed to reduce STIs, increase use of home-based STI testing, or reduce STI-risk behavior was conducted. Six databases were searched between January 2000 and October 2014. RESULTS: 17,916 articles were screened. 23 RCTs of interventions for young people met our inclusion criteria. Significant STI reductions were found in four RCTs of interventions using brief one-to-one counselling (2 RCTs), video (1 RCT) and a STI home-testing kit (1 RCT). Increase in STI test uptake was found in five studies using video (1 RCT), one-to-one counselling (1 RCT), home test kit (2 RCTs) and a web-based intervention (1 RCT). Reduction in STI-risk behavior was found in seven RCTs of interventions using digital online (web-based) and offline (computer software) (3 RCTs), printed materials (1 RCT) and video (3 RCTs). Ten RCTs of interventions for MSM met our inclusion criteria. Three tested for STI reductions but none found significant differences between intervention and control groups. Increased STI test uptake was found in two studies using brief one-to-one counselling (1 RCT) and an online web-based intervention (1 RCT). Reduction in STI-risk behavior was found in six studies using digital online (web-based) interventions (4 RCTs) and brief one-to one counselling (2 RCTs). CONCLUSION: A small number of interventions which could be used, or adapted for use, in sexual health clinics were found to be effective in reducing STIs among young people and in promoting self-reported STI-risk behavior change in MSM. PMID- 27373210 TI - Evaluation of a Staff Training Programme using Positive Psychology coaching with film and theatre elements in care homes: views and attitudes of residents, staff and relatives. AB - BACKGROUND: There is a recognised need to improve staff training in care homes. The aim of this study was to conduct a qualitative evaluation of the Ladder to the Moon Culture Change Studio Engagement Programme (CCSEP), a staff training programme aimed at enhancing staff-resident communication. METHOD: Focus groups were conducted with residents able to provide consent; staff and relatives and managers were interviewed in two care homes. A theoretical framework was developed to interpret the impact of CCSEP using Framework Analysis. RESULTS: Residents noted that the programme appeared to result in staff interacting more with them, as well as enjoying working together as a team. Staff reported an improved sense of teamwork, developing more positive attitudes towards residents, as well as their concerns about using theatrical techniques in the care setting. Relatives identified care home organisational aspects as being barriers to implementation, and some regarded CCSEP simply as 'entertainment' rather than 'creative care'. DISCUSSION: This study provides an insight into the potential of this staff training programme to improve staff-resident interactions. However, participants' varying views of CCSEP highlight the need to brief staff, residents and relatives before implementation so as to enable full understanding of the aim. PMID- 27373211 TI - Colonisation of basal cell carcinoma by lentigo maligna: a case report, review of the literature, and series follow-up. AB - BACKGROUND: Melanocytic tumours which colonise basal cell carcinomas (BCC) may be considered as either lentigo maligna (LM) (in situ) or invasive melanomas. OBJECTIVES: To highlight the diagnostic approach and long-term prognosis of LM which colonises BCC. MATERIALS AND METHODS: Using Satter et al.'s classification, we identified a case of BCC colonised by LM and reviewed similar cases in the literature with long-term follow-up. RESULTS: In the absence of melanocytic extension beyond the lamina propria of the BCC compartment, mixed tumours may be considered as LM colonising the BCC, allowing for less invasive surgery. The absence of long-term relapse in our short series supports this diagnosis, rather than invasive melanomas. CONCLUSION: Our case report, review of the literature, and series follow-up illustrate the most recent assessment of melanocytic/BCC tumours, and guide the physician and the pathologist in their recognition and classification, thus allowing them to make the most appropriate therapeutic decisions. PMID- 27373212 TI - Targeting of MCT1 and PFKFB3 influences cell proliferation and apoptosis in bladder cancer by altering the tumor microenvironment. AB - Phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) and monocarboxylate transporter 1 (MCT1) play important roles in tumor endothelial cells (ECs) and several biological processes. The present study was conducted to study the effects of PFKFB3 and MCT1 on cell proliferation and apoptosis in the tumor microenvironment by co-culture of HUVECs and T24, a bladder cancer (BC) cell line, using a microfluidic device. Immunofluorescence assay showed that HUVEC activity was significantly enhanced under co-culture with T24 cells, according to the stronger fluorescence intensity of CD31 and CD105 than that in the signal cultured cells. Quercetin treatment inhibited MCT1 expression but did not affect PFKFB3 expression. Knockdown of MCT1 or/and PFKFB3 increased the apoptosis rate of the HUVECs under single-culture and co-culture situations by staining with calcein and propidium iodide. Meanwhile, cell proliferation and lactic concentration were significantly decreased after the blocking of MCT1 or/and PFKFB3, as compared with that in the control group. No obvious differences in the effects on apoptosis, proliferation and lactic concentration were found between cells treated with quercetin and siMCT1. Thus, we concluded that the targeting of MCT1 and PFKFB3 regulated cell proliferation and apoptosis in BC cells by altering the tumor microenvironment, and quercetin exhibited a potential antitumor effect by targeting MCT1. PMID- 27373213 TI - Comprehensive characterization of C-glycosyl flavones in wheat (Triticum aestivum L.) germ using UPLC-PDA-ESI/HRMSn and mass defect filtering. AB - A comprehensive characterization of C-glycosyl flavones in wheat germ has been conducted using multi-stage high resolution mass spectrometry (HRMSn ) in combination with a mass defect filtering (MDF) technique. MDF performed the initial search of raw data with defined C-glycosyl flavone mass windows and mass defect windows to generate the noise-reduced data focusing on targeted flavonoids. The high specificity of the exact mass measurement permits the unambiguous discrimination of acyl groups (nominal masses of 146, 162 and 176.) from sugar moieties (rhamnose, glucose or galactose and glucuronic acid). A total of 72 flavone C-glycosyl derivatives, including 2 mono-C-glycosides, 34 di-C glycosides, 15 tri-glycosides, 14 acyl di-C-glycosides and 7 acyl tri-glycosides, were characterized in wheat germ, some of which were considered to be important marker compounds for differentiation of whole grain and refined wheat products. The 7 acylated mono-O-glycosyl-di-C-glycosyl flavones and some acylated di-C glycosyl flavones are reported in wheat for the first time. The frequent occurrence of numerous isomers is a remarkable feature of wheat germ flavones. Both UV and mass spectra are needed to maximize the structure information obtained for data interpretation. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27373214 TI - Defective regulation of POMC precedes hypothalamic inflammation in diet-induced obesity. AB - Obesity is the result of a long-term positive energy balance in which caloric intake overrides energy expenditure. This anabolic state results from the defective activity of hypothalamic neurons involved in the sensing and response to adiposity. However, it is currently unknown what the earliest obesity-linked hypothalamic defect is and how it orchestrates the energy imbalance present in obesity. Using an outbred model of diet-induced obesity we show that defective regulation of hypothalamic POMC is the earliest marker distinguishing obesity prone from obesity-resistant mice. The early inhibition of hypothalamic POMC was sufficient to transform obesity-resistant in obesity-prone mice. In addition, the post-prandial change in the blood level of beta-endorphin, a POMC-derived peptide, correlates with body mass gain in rodents and humans. Taken together, these results suggest that defective regulation of POMC expression, which leads to a change of beta-endorphin levels, is the earliest hypothalamic defect leading to obesity. PMID- 27373215 TI - Evaluating use of higher dose oxybutynin in combination with desmopressin for refractory nocturnal enuresis. AB - INTRODUCTION: Nocturnal enuresis is a common pediatric condition with limited treatment options. In older children, pharmacologic therapy is often the preferred treatment. Pharmacologic therapies including desmopressin (DDAVP) or imipramine are effective in 40-50% of children. However, imipramine has serious safety concerns. Desmopressin in combination with a fixed dose anticholinergic has been shown to be useful in individuals who fail desmopressin monotherapy, but still fails to achieve success rates greater than 60%. OBJECTIVE: The goal was to explore the efficacy and safety of using combination therapy desmopressin plus oxybutynin with increasing dose of oxybutynin in patients refractory to standard combination therapy. STUDY DESIGN: This was a single institution, IRB-approved, retrospective chart review of 61 patients (ages 7-18 years) including those with monosymptomatic primary nocturnal enuresis and non-monosymptomatic enuresis with controlled daytime voiding symptoms (CDVS) treated initially with desmopressin. All patients who failed initial therapy with desmopressin were started on combination therapy desmopressin (0.6 mg) plus standard dose (5 mg) oxybutynin. In patients who failed standard combination therapy, the dose of oxybutynin was titrated upwards until a response or the maximum dose of 10 mg was achieved. Demographic and medical history data were evaluated to determine predictive factors associated with response/failure to different therapy groups. RESULTS: The use of escalating doses of oxybutynin in combination with desmopressin achieved an overall response rate of 96.7% defined as a 2-week period without any enuretic events following initiation of treatment. Low-dose combination therapy (LDCT) (0.6 mg of desmopressin+5 mg of oxybutynin) had a response rate of 68% (Table). Advanced dose combination therapy (ADCT) (0.6 mg of desmopressin+7.5-10 mg of oxybutynin) had a response rate of 75.0%. A statistically significant relationship was found correlating both attention deficit disorder/attention deficit hyperactivity disorder(ADD/ADHD) and CDVS with failure on monotherapy. No patients in the study reported any adverse events or side effects from the medications. DISCUSSION: The overall success rate of 96.7% with titrated doses of oxybutynin in combination with desmopressin is considerably higher than the response rates on fixed dose combination therapy quoted in the literature and supports the need for further evaluation in larger studies. Additionally, we found a statistically significant association between monotherapy failure and children with either ADD/ADHD or controlled daytime voiding symptoms. Our study is limited by small numbers and larger studies are needed to confirm these results. CONCLUSION: Our results suggest that ADCT is a safe and effective treatment option for primary nocturnal enuresis refractory to standard and low dose combination therapy. PMID- 27373216 TI - ABF2, ABF3, and ABF4 Promote ABA-Mediated Chlorophyll Degradation and Leaf Senescence by Transcriptional Activation of Chlorophyll Catabolic Genes and Senescence-Associated Genes in Arabidopsis. AB - Chlorophyll (Chl) degradation is an integral process of leaf senescence, and NYE1/SGR1 has been demonstrated as a key regulator of Chl catabolism in diverse plant species. In this study, using yeast one-hybrid screening, we identified three abscisic acid (ABA)-responsive element (ABRE)-binding transcription factors, ABF2 (AREB1), ABF3, and ABF4 (AREB2), as the putative binding proteins of the NYE1 promoter. Through the transactivation analysis, electrophoretic mobility shift assay, and chromatin immunoprecipitation, we demonstrated that ABF2, ABF3, and ABF4 directly bound to and activated the NYE1 promoter in vitro and in vivo. ABA is a positive regulator of leaf senescence, and exogenously applied ABA can accelerate Chl degradation. The triple mutant of the ABFs, abf2abf3abf4, as well as two ABA-insensitive mutants, abi1-1 and snrk2.2/2.3/2.6, exhibited stay-green phenotypes after ABA treatment, along with decreased induction of NYE1 and NYE2 expression. In contrast, overexpression of ABF4 accelerated Chl degradation upon ABA treatment. Interestingly, ABF2/3/4 could also activate the expression of two Chl catabolic enzyme genes, PAO and NYC1, by directly binding to their promoters. In addition, abf2abf3abf4 exhibited a functional stay-green phenotype, and senescence-associated genes (SAGs), such as SAG29 (SWEET15), might be directly regulated by the ABFs. Taken together, our results suggest that ABF2, ABF3, and ABF4 likely act as key regulators in mediating ABA-triggered Chl degradation and leaf senescence in general in Arabidopsis. PMID- 27373217 TI - Congenital hereditary endothelial dystrophy, not glaucoma, in a child with iris colobomas. AB - Corneal haze and elevated measured intraocular pressure in a young child with iris abnormalities are suggestive for glaucoma, but primary corneal disease is another possibility. We highlight the case of a 10-year-old boy with these clinical signs who was initially treated for glaucoma but in fact had congenital hereditary endothelial dystrophy, iris colobomas, and no glaucoma. PMID- 27373218 TI - Staffing and the incidence of pressure ulcers in German hospitals: A multicenter cross-sectional study. AB - In this study, we investigated the association between nurse and physician staffing and the incidence of hospital-acquired pressure ulcers in acute care hospitals in Germany. The study population, derived from the Quality Reports of German Hospitals and the Hospital Directory, consisted of 710 hospitals covering 716,281 cases in the first quarter of 2010, and 672 hospitals covering 757,665 cases in the first quarter of 2012. The relationship between staffing variables and the standardized incidence ratios of pressure ulcers was examined using bivariate and multivariable linear regression models. Estimates were controlled for several patient and hospital characteristics. The total number of nurses and physicians per 100 beds did not show significant associations with outcome variables. However, the proportion of nurses with at least 3 years of training to total nursing staff was inversely associated with the incidence of pressure ulcers at hospital level, indicating a higher efficacy of pressure ulcer prevention measures. PMID- 27373219 TI - Habitat use of bats in relation to wind turbines revealed by GPS tracking. AB - Worldwide, many countries aim at countering global climate change by promoting renewable energy. Yet, recent studies highlight that so-called green energy, such as wind energy, may come at environmental costs, for example when wind turbines kill birds and bats. Using miniaturized GPS loggers, we studied how an open-space foraging bat with high collision risk with wind turbines, the common noctule Nyctalus noctula (Schreber, 1774), interacts with wind turbines. We compared actual flight trajectories to correlated random walks to identify habitat variables explaining the movements of bats. Both sexes preferred wetlands but used conventionally managed cropland less than expected based on availability. During midsummer, females traversed the land on relatively long flight paths and repeatedly came close to wind turbines. Their flight heights above ground suggested a high risk of colliding with wind turbines. In contrast, males recorded in early summer commuted straight between roosts and foraging areas and overall flew lower than the operating range of most turbine blades, suggesting a lower collision risk. Flight heights of bats suggest that during summer the risk of collision with wind turbines was high for most studied bats at the majority of currently installed wind turbines. For siting of wind parks, preferred bat habitats and commuting routes should be identified and avoided. PMID- 27373220 TI - Human chondroprogenitors in alginate-collagen hybrid scaffolds produce stable cartilage in vivo. AB - The goal of this study was to evaluate human epiphyseal chondroprogenitor cells (ECPs) as a potential new cell source for cartilage regeneration. ECPs were compared to human bone marrow stromal cells (MSCs) and human adult articular chondrocytes (ACs) for their chondrogenic potential and phenotypic stability in vitro and in vivo. The cells were seeded in Optimaix-3D scaffolds at 5 * 104 cells/mm3 and gene expression, matrix production and mechanical properties were analysed up to 6 weeks. In vitro, ECPs synthesized consistently high collagen 2 and low collagen 10. AC-seeded constructs exhibited high donor variability in GAG/DNA values as well as in collagen 2 staining, but showed low collagen 10 production. MSCs, on the other hand, expressed high levels of collagen 2 but also of collagens 1 and 10, and were therefore not considered further. In vivo, there was considerable loss of matrix proteins in ECPs compared to in vitro cultured samples. To overcome this, a second implantation study investigated the effect of mixing cells with alginate prior to seeding in the scaffold. ECPs in alginate maintained their cartilage matrix and resisted mineralization and vessel infiltration better 6 weeks after subcutaneous implantation, whereas ACs lost their chondrogenic matrix completely. This study shows the great potential of ECPs as an off-the-shelf, highly chondrogenic cell type that produces stable cartilage in vivo. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27373221 TI - In Situ Formation of Crystallographically Oriented Semiconductor Nanowire Arrays via Selective Vaporization for Optoelectronic Applications. AB - Direct transformation of bulk crystals to single-crystalline crystallographically oriented semiconductor nanowire arrays is presented. Real-time imaging during in situ environmental scanning electron microscopy experiment clearly demonstrates that the nanowire arrays form through a selective vaporization process with respect to the crystallography of wurtzite crystals. Due to the high quality of the prepared semiconductor nanowire arrays, photodetectors constructed from them can present superior optoelectronic performances. PMID- 27373222 TI - Is a blood filled heart more susceptible to electric shock? PMID- 27373223 TI - Public-access AED pad application and outcomes for out-of-hospital cardiac arrests in Osaka, Japan. AB - BACKGROUND: Actual application of public-access automated external defibrillator (AED) pads to patients with an out-of-hospital cardiac arrest (OHCA) by the public has been poorly investigated. METHODS: AED applications, prehospital characteristics, and one-month outcomes of OHCAs occurring in Osaka Prefecture from 2011 to 2012 were obtained from the Utstein Osaka Project registry. Patients with a non-traumatic OHCA occurring before emergency medical service attendance were enrolled. The proportion of AED pads that were applied to the patients' chests by the public and one-month outcomes were analysed according to the location of OHCA. RESULTS: In total, public-access AED pads were applied to 3.5% of OHCA patients (351/9978) during the study period. In the multivariate analyses, OHCAs that occurred in public places and received bystander-initiated cardiopulmonary resuscitation were associated with significantly higher application of public-access AEDs. Among the patients for whom public-access AED pads were applied, 29.6% (104/351) received public-access defibrillation. One month survival with a favourable neurological outcome was significantly higher among patients who had an AED applied compared to those who did not (19.4% vs. 3.0%; OR: 2.76 [95% CI: 1.92-3.97]). CONCLUSION: The application of public-access AEDs leads to favourable outcomes after an OHCA, but utilisation of available equipment remains insufficient, and varies considerably according to the location of the OHCA event. Alongside disseminating public-access AEDs, further strategic approaches for the deployment of AEDs at the scene, as well as basic life support training for the public are required to improve survival rates after OHCAs. PMID- 27373224 TI - Reply to letter: "Is a blood filled heart more susceptible to electric shock?". PMID- 27373225 TI - Ice nucleation of an insect lipoprotein ice nucleator (LPIN) correlates with retardation of the hydrogen bond dynamics at the myo-inositol ring. AB - Remarkably little is known about the mechanism of action of ice nucleation proteins (INPs), although their ability to trigger ice nucleation could be used in a broad variety of applications. We present CD measurements of an insect lipoprotein ice nucleator (LPIN) which show that the lipoproteins consist of a high amount of beta-structures (35%). Terahertz absorption spectroscopy is used to probe the influence of the LPIN on the H-bond network dynamics. We observe a small, but significant THz excess, as an indication of an influence on the H-bond network dynamics. When adding the ice nucleation inhibitor sodium borate, this effect is considerably reduced, similar to that observed before for antifreeze glycoproteins (AFGPs). We propose that myo-inositol, the functional group of phosphatidylinositols, is crucial for the observed change of the H-bond network dynamics of hydration water. This hypothesis is confirmed by additional THz experiments which revealed that the influence of myo-inositol on the hydrogen bond network can be blocked by sodium borate, similar to the case of LPINs. Interestingly, we find a less significant effect when myo-inositol is replaced for chiro- and allo-inositol which underlines the importance of the exact positioning of the OH groups for the interaction with the H-bond network. We propose that a local ordering of water molecules is supporting ice nucleation activity for the LPIN in a similar way to that found for AFP activity in the case of hyperactive insect AFPs. PMID- 27373226 TI - Hydrogenation vs. H-D isotope scrambling during the conversion of ethylene with hydrogen/deuterium catalyzed by platinum under single-collision conditions. AB - The catalytic hydrogenation of olefins promoted by transition metals, represented here by the conversion of ethylene with platinum, was studied under a unique regime representing pressures in the mTorr range and single-collision conditions. Isotope labeling was used to follow the concurrent H-D exchange steps that occur during this conversion. Multiple isotope substitutions were observed in the resulting ethane products, reflecting the operability of the reversible stepwise mechanism proposed a long time ago by Horiuti and Polanyi. In fact, the ethane isotopologue distributions obtained in these experiments reflect a much higher probability for the dehydrogenation of ethyl intermediates back to the olefin, relative to the hydrogenation to ethane, than typically seen in this catalysis. In addition, a second mechanistic pathway was clearly identified, responsible for most of the dideuteroethane produced. Based on the dependence of the rates of formation of each isotopologue on the fluxes of deuterium and ethylene, it is argued that this second route may be a "reverse" Eley-Rideal step between gas phase ethylene and two deuterium atoms adsorbed on adjacent sites of the platinum surface. The clear identification of this second pathway is new, and was possible thanks to our ability to explore a new single-collision intermediate pressure regime. PMID- 27373227 TI - Applications of graphene and its derivatives in intracellular biosensing and bioimaging. AB - Graphene has a unique planar structure, as well as excellent electronic properties, and has attracted a great deal of interest from scientists. Graphene and its derivatives display advantageous characteristics as a biosensing platform due to their high surface area, good biocompatibility and ease of functionalization. Moreover, graphene and its derivatives exhibit excellent optical properties; thus they are considered to be promising and attractive candidates for bioimaging, mainly of cells and tissues. Following an introduction and a discussion of the optical properties of graphene, this review assesses the methods for engineering the functions of graphene and its derivatives. Specific examples are given on the use of graphene and its derivatives in fluorescence bioimaging, surface-enhanced Raman scattering (SERS) imaging, and magnetic resonance imaging (MRI). Finally, the prospects and further developments in this exciting field of graphene-based materials are suggested. PMID- 27373228 TI - Gold-catalysed facile access to indene scaffolds via sequential C-H functionalization and 5-endo-dig carbocyclization. AB - A concise synthesis of functionalized indene derivatives via the gold(i) catalysed cascade C-H functionalization/conia-ene type reaction of electron-rich aromatics with o-alkynylaryl alpha-diazoesters has been developed. In this transformation, the gold catalyst not only catalysed the formation of the zwitterionic intermediate via intermolecular C-H functionalization but promoted the subsequent intramolecular 5-endo-dig cyclization via activation of alkynes. The reaction is characterized by high chemo- and site-selectivity, readily available starting materials, nice functional-group tolerance and mild reaction conditions. PMID- 27373229 TI - Effects of acute dietary nitrate supplementation on aortic blood pressure and aortic augmentation index in young and older adults. AB - PURPOSE: Aging is associated with elevated blood pressure (peripheral and aortic; BP) and aortic augmentation index (AIx) which may contribute to aortic BP. Although inorganic nitrate consumption reduces peripheral BP in both young and older adults, the effects of nitrate consumption on aortic BP and wave reflection in young and older adults is unknown. Therefore, we sought to characterize the effects of nitrate consumption on aortic BP and AIx in young and older adults. METHODS: Noninvasive aortic pressure waveforms were synthesized from high fidelity radial pressure waveforms via applanation tonometry before and following (60, 90, 120, 150, and 180 min) consumption of a nitrate-rich beetroot juice in 26 healthy adults (young: 25 +/- 4 years, n = 14; older: 64 +/- 5 years, n = 12). Aortic BP and indices of aortic wave reflection (AIx and AIx normalized for heart rate; AIx@75bpm) were calculated from the generated aortic pressure waveform. RESULTS: Nitrate consumption increased plasma nitrite in both groups 60-180 min following beetroot consumption (P < 0.001). Nitrate consumption reduced peripheral and aortic BP in both young and older adults (P < 0.05), with the change being similar between age groups. Conversely, indices of aortic wave reflection were reduced only in young adults following nitrate consumption (range of change from baseline over time: AIx@75bpm, -4.3 to -8.8%, P < 0.05), whereas aortic AIx remained unchanged in the older adults. CONCLUSIONS: Taken together, our results suggest that acute dietary nitrate supplementation reduces peripheral and aortic BP similarly in young and older adults despite differential effects on aortic AIx between age groups. PMID- 27373230 TI - Tumor Phenotype and Gene Expression During Early Mammary Tumor Development in Offspring Exposed to Alcohol In Utero. AB - BACKGROUND: Alcohol exposure in utero increases susceptibility to carcinogen induced mammary tumorigenesis in adult offspring and causes tumors with a more malignant phenotype. This study was conducted to identify changes early in tumor development that might lead to this outcome. METHODS: Pregnant Sprague-Dawley rats were fed a liquid diet containing 6.7% ethanol (alcohol), an isocaloric liquid diet without alcohol (pair-fed), or rat chow ad libitum (ad lib) from gestation day 7 until parturition. At birth, female progeny were cross-fostered to control dams. Pups were weaned at postnatal day (PND) 21 and fed rat chow ad libitum for the remainder of the experiment. Female offspring were administered N nitroso-N-methylurea (NMU; 50 mg/kg body weight) on PND 50. Mammary glands were palpated weekly, and offspring were euthanized at 16 weeks post-NMU injection. RESULTS: At 16 weeks post-NMU, tumor multiplicity was greater in alcohol-exposed offspring compared with control groups. Estrogen receptor-alpha (ER) mRNA expression was decreased in tumors from alcohol-exposed offspring, and these animals developed more ER-negative tumors relative to the pair-fed group. Alcohol exposed offspring also tended to develop more progesterone receptor (PR)-positive tumors. All tumors were HER2-negative. PR positivity was associated with higher Ki67 expression, suggesting that PR-positive tumors were more proliferative. Tumors from alcohol-exposed animals exhibited increased mRNA expression of the insulin-like growth factor (IGF) family members IGF-II and IGFBP-5. IGF-II and DNA methyltransferase mRNA tended to be greater in the normal contralateral mammary glands of these animals. CONCLUSIONS: These data indicate that alcohol exposure in utero may shift NMU-induced tumor development toward a more aggressive phenotype and that alterations in IGF-II expression may contribute to these changes. Additional studies should be aimed at epigenetic mechanisms that underlie IGF-II expression to further delineate how this gene is altered in mammary glands of adults exposed to alcohol in utero. PMID- 27373231 TI - Overexpression of Bmi1 in Lymphocytes Stimulates Skeletogenesis by Improving the Osteogenic Microenvironment. AB - To investigate whether overexpression of Bmi1 in lymphocytes can stimulate skeletogenesis by improving the osteogenic microenvironment, we examined the skeletal phenotype of EMUBmi1 transgenic mice with overexpression of Bmi1 in lymphocytes. The size of the skeleton, trabecular bone volume and osteoblast number, indices of proliferation and differentiation of bone marrow mesenchymal stem cells (BM-MSCs) were increased significantly, ROS levels were reduced and antioxidative capacity was enhanced in EMUBmi1 mice compared to WT mice. In PTHrP1-84 knockin (Pthrp(KI/KI)) mice, the expression levels of Bmi1 are reduced and potentially can mediate the premature osteoporosis observed. We therefore generated a Pthrp(KI/KI) mice overexpressing Bmi1 in lymphocytes and compared them with Pthrp(KI/KI) and WT littermates. Overexpression of Bmi1 in Pthrp(KI/KI) mice resulted in a longer lifespan, increased body weight and improvement in skeletal growth and parameters of osteoblastic bone formation with reduced ROS levels and DNA damage response parameters. Our results demonstrate that overexpression of Bmi1 in lymphocytes can stimulate osteogenesis in vivo and partially rescue defects in skeletal growth and osteogenesis in Pthrp(KI/KI) mice. These studies therefore indicate that overexpression of Bmi1 in lymphocytes can stimulate skeletogenesis by inhibiting oxidative stress and improving the osteogenic microenvironment. PMID- 27373232 TI - A Gordian knot: disentangling comorbidities in heart failure. PMID- 27373233 TI - Japanese Multicenter Outcomes With the HeartMate II Left Ventricular Assist Device in Patients With Small Body Surface Area. AB - BACKGROUND: The HeartMate II (HMII) continuous-flow LVAD was approved for Japanese health insurance coverage in April 2013 as a bridge to transplantation (BTT). We report on post-approval Japanese multicenter outcomes, and a comparison between patients with low and high body surface area (BSA). METHODS AND RESULTS: HMII LVAD was implanted in 104 consecutive patients at 15 Japanese centers between April 2013 and July 2014. Perioperative data were submitted to the Japanese Registry for Mechanically Assisted Circulatory Support. Patients were divided into 2 groups on the basis of BSA less or greater than 1.5 m(2). Survival outcomes, New York Heart Association functional class, and adverse event rates were compared between the 2 groups. Preoperative hemodynamics and INTERMACS profiles were similar between groups. There were more females and younger patients in the low BSA group. The respective 6-month and 1-year death- or pump exchange-free survival rates were excellent: 90% and 90% in the BSA <1.5 group vs. 90% and 85% in the BSA >=1.5 group. In the BSA <1.5 group, occurrence of hemorrhagic stroke was 10% and occurrence of embolic stroke was 0%, vs. 12% and 8% in BSA >=1.5 group. Driveline infection was encountered more frequently in the BSA <1.5 group. CONCLUSIONS: Results for HMII LVAD as BTT in the post-approval era showed excellent survival and functional capacity improvement. Of particular interest to the Japanese patient population are the excellent results in patients with small BSA. (Circ J 2016; 80: 1931-1936). PMID- 27373234 TI - Effects of Proximal Pulmonary Artery Occlusion on Pulsatile Right Ventricular Afterload in Rats. AB - BACKGROUND: In patients with proximal pulmonary artery (PA) thromboembolism, an increased PA resistance contributes to abnormal right ventricular (RV) afterload. However, the effects of proximal thromboembolism on the dynamic properties of RV afterload, which is determined by PA impedance, have not been analyzed quantitatively. The present study aimed to identify changes in PA impedance after the pulmonary perfusion volume was greatly reduced by unilateral proximal PA occlusion. METHODS AND RESULTS: Ten male Sprague-Dawley rats were used. PA flow and pressure waveforms were recorded during irregular pacing, before and 10 min after left PA occlusion. PA impedance was parameterized by using a three-element Windkessel model consisting of peripheral resistance (RP), arterial compliance (CP) and characteristic impedance (ZC). After proximal PA occlusion, PA impedance modulus increased over a frequency range of interest.ZCincreased significantly (after PA occlusion vs. baseline: 0.128+/-0.016 vs. 0.074+/-0.010 mmHg.min/ml, P<0.001), whereasCPandRPdid not change significantly. CONCLUSIONS: Proximal PA occlusion increasedZCwith the attenuation ofRPincrease andCPdecrease predicted from the decreased pulmonary perfusion volume. The insignificant changes inRPandCPindicate that a recruitment phenomenon may result in this attenuation. The existence of compensation by a recruitment mechanism suggests the relative importance of increasedZCin defining abnormal RV afterload in patients with proximal PA thromboembolism. (Circ J 2016; 80: 2010-2018). PMID- 27373235 TI - Hope or Hype - Does Cryoballoon Simplify Atrial Fibrillation Ablation Technique or Just Another Costly Toy? PMID- 27373236 TI - Motivational interviewing-based training enhances clinicians' skills and knowledge in psoriasis: findings from the Pso Well(r) study. AB - BACKGROUND: Psoriasis is a common long-term, immune-mediated skin condition associated with behavioural factors (e.g. smoking, excess alcohol, obesity), which increase the risk of psoriasis onset, flares and comorbidities. Motivational interviewing (MI) is an evidence-based approach to health-related behaviour change that has been used successfully for patients with long-term conditions. This study assessed change in clinicians' MI skills and psoriasis knowledge following Psoriasis and Wellbeing (Pso Well(r) ) training. OBJECTIVES: To investigate whether the Pso Well training intervention improves clinicians' MI skills and knowledge about psoriasis-related comorbidities and risk factors; and to explore the acceptability and feasibility of the Pso Well training content, delivery and evaluation. METHODS: Clinicians attended the 1-day training programme focused on MI skills development in the context of psoriasis. MI skills were assessed pre- and post-training using the Behaviour Change Counselling Index. Knowledge about psoriasis-related comorbidity and risk factors was assessed with a novel 22-point measure developed for the study. Interviews with clinicians were analysed qualitatively to identify perceptions about the feasibility and acceptability of the training. RESULTS: Sixty-one clinicians completed the training (35 dermatology nurses, 23 dermatologists and three primary-care clinicians). Clinicians' MI skills (P < 0.001) and knowledge (P < 0.001) increased significantly post-training. Clinicians found the training valuable and relevant to psoriasis management. CONCLUSIONS: Attendance at the Pso Well training resulted in improvements in clinicians' knowledge and skills to manage psoriasis holistically. Clinicians deemed the training itself and the assessment procedures used both feasible and acceptable. Future research should investigate how this training may influence patient outcomes. PMID- 27373237 TI - Effect of video lag on laparoscopic surgery: correlation between performance and usability at low latencies. AB - BACKGROUND: Few telesurgery studies assess the impact of latency on user experience, low latencies are often not studied despite evidence of negative effects, and some studies recruit inexperienced subjects instead of surgeons without evidence that latency affects both groups similarly. METHODS: Fifteen trainees and fourteen laparoscopic surgeons conducted two tasks on a laparoscopy home-trainer at six latencies below 200 milliseconds (ms). Completion time and usability (perceived awareness of latency, inefficiency, disturbance, adaptability, and impact on patient safety) were measured. RESULTS: Weak correlation between completion time and usability was found. There was significant deterioration in performance and user experience at 105 ms added latency. Surgeons were more negatively affected. CONCLUSION: Objective measures insufficiently describe the impact of latency therefore standard measures of user experience should be incorporated in studies. Even low latencies may be detrimental to laparoscopic surgery. Results from non-experts cannot predict the impact of latency on experienced surgeons. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27373238 TI - Die tumorimmunologische Revolution in der Behandlung des fortgeschrittenen Melanoms. PMID- 27373239 TI - Ausschreibung fur Forschungsprojekte zur Pathogenese, Diagnostik und Therapie der Sklerodermie. PMID- 27373240 TI - Nebenwirkungsmanagement bei Immun-Checkpoint-Blockade durch CTLA-4- und PD1 Antikorper beim metastasierten Melanom. PMID- 27373241 TI - Management of side effects of immune checkpoint blockade by anti-CTLA-4 and anti PD-1 antibodies in metastatic melanoma. AB - CTLA-4 and PD-1 are potential targets for tumor-induced downregulation of lymphocytic immune responses. Immune checkpoint-modifying monoclonal antibodies oppose these effects, inducing T cell-mediated immune responses to various tumors including melanoma. Both anti-CTLA-4 and anti-PD-1 antibodies modify the interaction between tumor, antigen-presenting cells, and T lymphocytes. With respect to overall survival, clinical studies have shown a major benefit for the anti-CTLA-4 antibody ipilimumab as well as the two anti-PD-1 antibodies nivolumab and pembrolizumab. Following approval of ipilimumab in 2011, the latter two achieved market authorization in the summer of 2015. Immune responses thus induced and enhanced inevitably entail autoimmune phenomena, affecting various organs to varying degrees. Knowledge of these side effects is crucial with regard to prevention and management by treating physicians. Typically occurring early on and presenting with pronounced and persistent diarrhea, colitis represents a major and severe side effect. Other immune-mediated disorders include dermatitis, hypophysitis, thyroiditis, hepatitis, iridocyclitis as well as other less common autoimmune phenomena. Early recognition and initiation of treatment can reduce risks and sequelae for patients. This review describes the mechanisms of action of immune checkpoint blockade as well as its clinical effects in metastatic melanoma, with a detailed focus on the spectrum of adverse events and their therapeutic management. PMID- 27373242 TI - Immune checkpoint inhibitors: a milestone in the treatment of melanoma. AB - It has been known for decades that the immune system is able to detect and destroy tumor cells. In the past, this knowledge - mostly acquired through animal experiments - could not be used to benefit our patients, because immuno oncological therapeutic approaches in humans had constantly failed over recent decades. With the exception of adjuvant interferon therapy, none of these approaches had found its way into everyday clinical practice, and only very few patients were able to enjoy long-term survival associated with good quality of life. With the advent of novel immunological approaches, the meaning of long-term survival as well as quality of life has been redefined for oncological patients. For the first time, a significant percentage of patients responds to treatment with immune checkpoint inhibitors, showing long-term remission and even cure. It has already become apparent that immunotherapy will in the future be one of the therapeutic mainstays in the treatment of metastatic melanoma as well as many other tumor types. The present review article presents the most important new treatment modalities, their mechanism of action, clinical data regarding treatment response, and adverse events to be expected. PMID- 27373243 TI - Checkpoint-Inhibitoren in der Immuntherapie: Ein Meilenstein in der Behandlung des malignen Melanoms. AB - Seit Jahrzehnten ist bekannt, dass Tumoren vom Immunsystem erkannt und zerstort werden konnen. Diese, vor allem in Tierversuchen gewonnene Erkenntnis konnte jedoch in der Vergangenheit nicht zum Nutzen unserer Patienten umgesetzt werden, da immunonkologische Therapieansatze in den letzten Jahrzehnten in der Anwendung beim Menschen stets versagt haben. Daher hat, mit Ausnahme der adjuvanten Interferontherapie, keines dieser Verfahren den Einzug in die klinische Versorgung gefunden. Langzeituberleben unter guter Lebensqualitat war dabei sehr wenigen Patienten vorbehalten. Mit den neuen immunologischen Therapieansatzen wird jedoch sowohl das Langzeituberleben als auch die Lebensqualitat onkologischer Patienten neu definiert. Auf die neuen "Immun-Checkpoint Inhibitoren" spricht erstmals ein relevanter Teil der behandelten Patienten an und diese zeigen in der Regel langandauernde Remissionen bis hin zur Heilung. Schon jetzt ist klar, dass die Immuntherapie in Zukunft eine der wesentlichen Therapiesaulen bei der Behandlung des metastasierten Melanoms und auch vieler anderer fortgeschrittener Tumoren bilden wird. In dieser Ubersicht werden die wichtigsten neuen Therapiemodalitaten besprochen und sowohl deren Wirkprinzip als auch klinische Daten zum Therapieansprechen und zu erwartenden Nebenwirkungen der Therapie referiert. PMID- 27373244 TI - Survey zu sensibilisierenden Inhaltsstoffen von oxidativen Haarfarben (Konsumenten- und Kabinettware) in Deutschland. AB - HINTERGRUND: Bestandteile oxidativer Haarfarben, wie z. B. p-Toluylendiamin, sind zum einen teils hochpotente Kontaktallergene, zum anderen sind zahlreiche Verbraucher, Friseurkunden bzw. Friseure exponiert. METHODIK: Survey zur Exposition gegenuber aktiven Komponenten oxidativer Haarfarben in Deutschland, basierend auf der Erfassung der qualitativen Produktrezeptur nach INCI, gesondert fur Konsumenten- und die in den Salons verwendete "Kabinett"-Ware, bei der auch das gemeinsame Vorkommen der Bestandteile dargestellt wird. ERGEBNISSE: Die 20 am haufigsten verwendeten Stoffe sind nahezu ausnahmslos starke oder sehr starke Sensibilisatoren; Spitzenreiter ist p-Toluylendiaminsulfat, das in 88 % aller Produkte enthalten ist. Zwischen Produkten im Einzelhandel und professionellen Produkten im Friseurfachhandel bestehen nur geringe Haufigkeitsunterschiede. Haufige Kombinationen bestehen zwischen p-Toluylendiamin, Resorcin sowie m Aminophenol, wobei die Einsatzkonzentrationen, die in dieser Studie nicht untersucht werden konnten, je nach Nuance sehr unterschiedlich sind. SCHLUSSFOLGERUNGEN: Die univariate Betrachtung zeigt, dass die aktuelle "Friseurstoff-Reihe" der Deutschen Kontaktallergie-Gruppe das Expositions Spektrum von Allergenen nicht gut abdeckt; uberdies legen auch Ergebnisse anderer Studien nahe, dass eine Reihe weiterer Allergene getestet werden sollte. Daruber hinaus bedarf der Effekt einer kombinierten Exposition gegenuber mehreren Allergenen gleichzeitig, mit der besonderen dynamischen Allergokinetik oxidativer Haarfarben, hinsichtlich des Sensibilisierungsrisikos weiterer Forschung. PMID- 27373245 TI - Survey of sensitizing components of oxidative hair dyes (retail and professional products) in Germany. AB - BACKGROUND: Components of oxidative hair dyes, such as p-toluylenediamine, are very potent contact sensitizers to which many consumers as well as hairdressers and their clients are commonly exposed. METHODS: Based on the qualitative composition of both retail and professional haircare products as determined by package labeling (according to INCI), we conducted a survey on the exposure to active components of oxidative hair dyes in Germany. The joint occurrence of components is also discussed. RESULTS: Nearly all of the 20 most commonly used substances are potent or very potent contact sensitizers. Contained in 88 % of all products, p-toluylenediamine is the most common component. There are only minor differences between retail and professional products. A frequent combination of substances includes p-toluylenediamine (sulfate), resorcinol as well as m-aminophenol. However, their actual concentrations (which were not investigated in this study) may vastly differ depending on the shade of the individual hair dye. CONCLUSIONS: Descriptive univariate analysis reveals that the currently used patch test series "Hairdressing Chemicals", as recommended by the German Contact Allergy Research Group (DKG), does not adequately cover the spectrum of allergens consumers and professionals are exposed to. Other studies have also suggested that a number of other allergens should be tested as well. Taking into account the dynamic kinetics of oxidative hair dyes with respect to allergy development, the effects of combined simultaneous exposure to multiple allergens on the risk of sensitization requires further research. PMID- 27373246 TI - Spirituelles Wohlbefinden und Coping bei Sklerodermie, Lupus erythematodes und malignem Melanom. AB - HINTERGRUND UND ZIELE: Religios-spirituelles Wohlbefinden ist verbunden mit hoherer Vitalitat und verminderter Depressionsneigung. In unserer Studie untersuchten wir die Strategien zur Krankheitsbewaltigung und die Rolle von Religiositat-Spiritualitat (R-S) zur Verbesserung des subjektiven Wohlbefindens. PATIENTEN UND METHODIK: 149 Patienten (107 Frauen), 44 mit systemischer Sklerodermie (SKL), 48 mit Lupus erythematodes (LE) und 57 mit malignem Melanom (MM), Stadium I-II, wurden mittels eines selbstentwickelten Fragebogens zum subjektiven Wohlbefinden, zu den mit der Erkrankung einhergehenden Umstanden sowie mit dem Multidimensionalen Inventar (MI-RSB) zu R-S befragt. ERGEBNISSE: LE Patienten sind zum Zeitpunkt der Diagnosestellung starker belastet als SKL- und MM-Patienten. SKL- und LE-Patienten konnen erst nach Jahren die Erkrankung akzeptieren. Der Gesamtscore des religios-spirituellen Befindens liegt bei LE Patienten signifikant unter dem Wert der Normalbevolkerung. Fotosensitivitat und Gelenksschmerzen sind bei LE-Patienten negativ assoziiert mit der Fahigkeit Vergeben zu konnen. SKL-Patienten mit Gesichtsveranderungen und Lungenbeteiligung zeigen hohere allgemeine Religiositat. MM-Patienten haben hohere Werte fur transzendente Hoffnung. SCHLUSSFOLGERUNGEN: Vortrage uber die Krankheit und psychologische Betreuung sind die wichtigsten Bedurfnisse von Patienten mit SKL, LE und MM an ihre Betreuer. Religios-spirituelle Angebote zur Krankheitsverarbeitung scheinen derzeit eine untergeordnete Rolle zu spielen, konnten aber eine wichtige Ressource sein, der man in Zukunft mehr Aufmerksamkeit schenken sollte. PMID- 27373247 TI - Spiritual well-being and coping in scleroderma, lupus erythematosus, and melanoma. AB - BACKGROUND AND OBJECTIVES: Religious/spiritual (R-S) well-being is associated with greater vitality and lower depression scores. In this study, we investigated strategies for coping with disease and the role of religiosity/spirituality with respect to improving subjective well-being. PATIENTS AND METHODS: One hundred and forty-nine patients (107 women), 44 of whom with systemic sclerosis (SSc), 48 with lupus erythematosus (LE), and 57 with stage I or II malignant melanoma (MM) were surveyed using a self-designed questionnaire, which addressed subjective well-being and disease-related circumstances, as well as the Multidimensional Inventory for Religious/Spiritual Well-Being (MI-RSWB). RESULTS: At the time of diagnosis, disease burden is greater in LE patients than in patients with SSc and MM. Only after several years are SSc and LE patients able to accept their disease. Compared with healthy individuals, the overall score of R-S well-being is significantly lower in LE patients. In LE, photosensitivity and joint pain are inversely correlated with the ability to forgive. SSc patients with facial lesions and pulmonary involvement show greater religiosity. MM patients display significantly higher values for transcendental hope. CONCLUSION: Talks about the disease and psychological support are the most important needs of patients with SSc, LE, and MM. At present, programs aimed at improving R-S coping skills do not seem to play a significant role, but could be an important resource that should be addressed in the future. PMID- 27373248 TI - Polyneuritic variant of pure neuritic leprosy with extensive involvement of peripheral nerves and sparing of the polio affected limb: a rare case report. PMID- 27373249 TI - Polyneuritische Variante einer rein neuritischen Lepra mit massiver Beteiligung der peripheren Nerven und Verschonung der von Polio betroffenen Extremitat: Ein seltenes Fallbeispiel. PMID- 27373250 TI - Primar kutane Diphtherie: Management, Diagnostik und therapeutische Konsequenzen anhand eines seltenen Fallberichts. PMID- 27373252 TI - Correspondence to Hirai I, Sakiyama T, Konohana A, et al. A case of neutrophilic dermatosis of the dorsal hand in acute leukemia - a distributional variant of Sweet's syndrome. PMID- 27373251 TI - Primary cutaneous diphtheria: management, diagnostic workup, and treatment as exemplified by a rare case report. PMID- 27373253 TI - Inzidenz epithelialer Proliferationen bei Vemurafenib-behandelten Patienten. PMID- 27373254 TI - Incidence of epithelial proliferations in patients treated with vemurafenib. PMID- 27373255 TI - Pityriasis versicolor atrophicans mit epidermaler Atrophie. PMID- 27373256 TI - Limited availability of diagnostic allergens for patch testing compromises patient care. PMID- 27373257 TI - Eingeschrankte Verfugbarkeit diagnostischer Epikutantest-Allergene gefahrdet die Patientenversorgung. PMID- 27373258 TI - Multiple eruptive Angiofibrome bei einem 14-jahrigen Madchen. PMID- 27373259 TI - Multiple eruptive angiofibromas in a 14-year-old girl. PMID- 27373260 TI - Unklare Nabelveranderung mit Induration. PMID- 27373261 TI - Unclear periumbilical infiltration with induration. PMID- 27373262 TI - Retroaurikular gestielte Lappenplastik zur Rekonstruktion grobetaer Ohrhelix- und Anthelixdefekte. PMID- 27373263 TI - Retroauricular pedicled flap for reconstruction of large helix and antihelix defects. PMID- 27373268 TI - Konferenzkalender in der gedruckten Ausgabe des JDDG. PMID- 27373270 TI - Kongresskalender 2016. PMID- 27373269 TI - Anmerkung zur Printausgabe Juni 2016. PMID- 27373271 TI - Bilateral pedicle anterolateral thigh (ALT) flap combined with bilateral sartorius muscle flap for reconstruction of extensive perineoscrotal and medial thigh defect because of Fournier's gangrene. AB - Fournier's gangrene is an acute and potentially lethal necrotizing fasciitis that can lead to extensive defects of the perineoscrotal area and lower abdominal wall as well. Such defect poses challenging tasks for both functional and cosmetic reconstruction. Local perforator pedicle flaps and muscle flaps can be employed and combined for such a reconstruction. In this report we present a case of reconstruction of a massive perineoscrotal and upper medial thigh defect because of Fournier's gangrene using a bilateral pedicle anterolateral thigh (ALT) flap and sartorius muscle flap. A 61 year-old male who suffered from Fournier's gangrene resulted in a perineal, scrotal, and medial thigh defect of 27 * 30 cm2 with exposure of the femoral vessels. A bilateral pedicle ALT flap measuring 30 * 9 cm2 based on two perforators and a bilateral sartorius muscle flap were harvested for soft tissue defect reconstruction and inguinal vessels coverage, respectively. The flaps survived completely, with no recipient or donor site morbidity. The length of follow-up was 6 months and was uneventful. A bilateral pedicle ALT flap combined with bilateral sartorius flap may be considered as a valid and safe option for an extensive inguinal and perineoscrotal reconstruction in selected cases. (c) 2016 Wiley Periodicals, Inc. Microsurgery 37:669-673, 2017. PMID- 27373272 TI - Mechanisms of SU5416, an inhibitor of vascular endothelial growth factor receptor, as a radiosensitizer for colon cancer cells. AB - Colorectal cancer is one of the most common cancers worldwide. Previous studies suggest that chemoradiotherapy is more effective for the treatment of colorectal cancer than is radiotherapy or chemotherapy alone. To enhance the radiosensitivity of tumor cells, several investigators have used targeted therapeutic agents that act as radiosensitizers. In the present study, we provide a scientific rationale for the clinical application of SU5416, an inhibitor of vascular endothelial growth factor receptor-2, as a radiosensitizer for colorectal cancer. Two human colorectal adenocarcinoma cell lines, HCT116 and HT 29, were treated with SU5416 and radiation alone or radiation followed by SU5416. In vitro tests were performed using colony forming assays, flow cytometric analysis, immunohistochemistry, senescence-associated beta-galactosidase, tumor cell motility and invasion assays. The combination of radiation and SU5416 synergistically inhibited cell survival and induced apoptosis through reactive oxygen species, enhanced IR-induced premature senescence, and inhibited DNA repair activity, cell migration and invasion. Collectively, our results favor the use of SU5416 and radiotherapy as a combination therapy for the treatment of colon cancer and it can be combined successfully with a radiation regimen to potentiate its antitumor and antimetastatic activities for future clinical trials. PMID- 27373273 TI - Effects of losartan on experimental varicocele-induced testicular germ cell apoptosis. AB - To investigate the potential protective effects of losartan on varicocele-induced germ cell apoptosis, 24 adult male Sprague Dawley rats were divided into three groups: a sham operation was performed in SHAM group, and experimental left varicocele was created in VAR and VAR + LOS groups. Additionally, in VAR + LOS group, losartan was administered for 30 days starting on the day of surgery. At the end of 30 days, all animals were sacrificed and left orchiectomy was performed. Testicular injury and spermatogenesis were evaluated according to Johnsen scoring system. To assess the nitrosative stress, immunohistochemical staining for endothelial nitric oxide synthase was used and evaluated by H-score and apoptotic index (AI) of germ cells was analysed by TUNEL method. A significant decrease in the mean Johnsen score (JS) was observed in VAR group compared with SHAM (p < .001). The mean H-score and AI were significantly higher in VAR group compared with SHAM (p < .001). After losartan administration, mean JS was significantly increased (p < .001) and mean H-score and AI were significantly decreased compared with VAR group (p < .001 and .01, respectively). Findings of this suggest that losartan acts as a potent protective agent against varicocele-induced germ cell apoptosis. PMID- 27373274 TI - Structure and activation of pro-activin A. AB - Activins are growth factors with multiple roles in the development and homeostasis. Like all TGF-beta family of growth factors, activins are synthesized as large precursors from which mature dimeric growth factors are released proteolytically. Here we have studied the activation of activin A and determined crystal structures of the unprocessed precursor and of the cleaved pro-mature complex. Replacing the natural furin cleavage site with a HRV 3C protease site, we show how the protein gains its bioactivity after proteolysis and is as active as the isolated mature domain. The complex remains associated in conditions used for biochemical analysis with a dissociation constant of 5 nM, but the pro-domain can be actively displaced from the complex by follistatin. Our high-resolution structures of pro-activin A share features seen in the pro-TGF-beta1 and pro-BMP 9 structures, but reveal a new oligomeric arrangement, with a domain-swapped, cross-armed conformation for the protomers in the dimeric protein. PMID- 27373275 TI - How do different designs of femoral stem affect total hip arthroplasty applied to Crowe type III and type IV dysplastic hips. AB - PURPOSE: A comparison was made of the clinical and radiological results of cylindrical fully porous-coated femoral stems (Group A) and Zweymuller-type femoral stems (Group B) used for the treatment of hip osteoathrosis, secondary to Crowe III and IV dysplasia, with total hip arthroplasty combined with femoral transverse shortening osteotomy. METHOD: This study is a retrospective evaluation of 86 hips in 50 patients. Group A comprised of 43 hips and Group B comprised of 43 hips. During final follow-up evaluation, patients were clinically assessed with Harris Hip Score (HHS), Merle d'Aubigne-Postel scale (MAP), and SF-36 scale. For radiological examination the Gulman THA score was used. Femoral osteotomy union, osteolysis around the components and component migration were also recorded and evaluated. RESULTS: In Group B, nonunion of the osteotomy site was found in 18.6% and delayed union in 20.9% of the hips. In Group A, delayed union was found in 7% of the hips. Patients' mean daily walking distance was found to be lower in Group A when compared to Group B. When the postoperative clinical HSS, and MAP and the radiological Gulman scores were compared, no statistically significant differences (p = 0.275) were found. CONCLUSIONS: Patients with hip osteoarthritis secondary to Crowe III and IV dysplasia, who were treated with THA and transverse osteotomy showed a higher incidence of osteotomy complications when the Zweymuller femoral stem was used. However, these complications did not affect clinical outcomes. PMID- 27373276 TI - Similar rate of infection eradication for functional articulating, prefabricated and custom-made spacers in 2-stage revision of the infected total hip: a literature review. AB - BACKGROUND: 2-stage revision with the use of an antibiotic-loaded interval spacer is therapy of choice in late periprosthetic joint infection for most surgeons. For the spacer, either a prefabricated, functional articulating or custom-made spacer can be used. Little is known about which type of spacer provides optimal outcome after 2-stage revision. The aim of this study was to determine which type of spacer provides the best results, when used in 2-stage revision of an infected THA. METHODS: We performed a systematic review of the literature to analyse which type of interval spacer provides highest infection eradication rate and best functional outcome after a minimum 2 year follow-up. Exclusion criteria were follow-up of less than 2 years, single-stage revision, or 2-stage revision without use of a spacer. RESULTS: 25 studies were included. Infection eradication rate was similar with rates of 96%, 93% and 95% for the prefabricated-, functional articulating- and custom-made spacers respectively. Functional outcome was scarcely described. Postoperative HHS was 81, 90 and 83 respectively. CONCLUSIONS: Functional articulating spacers achieve a comparable rate of infection eradication in the treatment of periprosthetic hip joint infections as compared to preformed or custom-made antibiotic-loaded spacers. There is insufficient evidence concerning rehabilitation and functional outcome after 2 stage revision hip arthroplasty to advocate or discourage the use of either kind of interval spacer. PMID- 27373277 TI - Hydrodynamic coupling of particle inclusions embedded in curved lipid bilayer membranes. AB - We develop theory and computational methods to investigate particle inclusions embedded within curved lipid bilayer membranes. We consider the case of spherical lipid vesicles where inclusion particles are coupled through (i) intramembrane hydrodynamics, (ii) traction stresses with the external and trapped solvent fluid, and (iii) intermonolayer slip between the two leaflets of the bilayer. We investigate relative to flat membranes how the membrane curvature and topology augment hydrodynamic responses. We show how both the translational and rotational mobility of protein inclusions are effected by the membrane curvature, ratio of intramembrane viscosity to solvent viscosity, and intermonolayer slip. For general investigations of many-particle dynamics, we also discuss how our approaches can be used to treat the collective diffusion and hydrodynamic coupling within spherical bilayers. PMID- 27373278 TI - A118G Polymorphism in MU-Opioid Receptor Gene and Interactions with Smoking and Drinking on Risk of Oesophageal Squamous Cell Carcinoma. AB - AIM: To investigate the single nucleotide polymorphism (SNP) of A118G and its interaction with smoking and drinking on oesophageal squamous cell carcinoma (ESCC) risk. METHODS: A total of 960 subjects (545 males and 415 females) with a mean age of 58.1 +/- 13.4 years were selected, including 490 ESCC patients and 470 normal control subjects. A logistic regression model was used to examine the association between A118G and ESCC and its interaction with A118G and current smoking and drinking. The odds ratio (OR) and 95% confident interval (95%CI) were calculated. RESULTS: The frequency for the A allele of A118G was significantly higher in ESCC cases, OR (95%CI) = 1.22 (1.08-1.59). Logistic regression analysis showed a significant association between the A allele in A118G and increased ESCC risk. The ESCC risk was significantly higher in carriers of the A allele of the A118G polymorphism than those with GG (AG + AA vs. GG, adjusted OR (95%CI) = 1.20 (1.05-1.53)). We found that current smokers with AG or AA of the A118G genotype have the highest ESCC risk compared with never smokers with a GG genotype; the OR (95%CI) was 2.57 (1.66-3.33). Current drinkers with AG or AA of the A118G genotype have the highest ESCC risk compared with not currently drinking subjects with the GG genotype, OR (95%CI) = 2.36 (1.47-3.25), after adjusting for covariates. CONCLUSION: The A allele of A118G and ESCC and additional interaction between the A allele of A118G and smoking or drinking were associated with increased ESCC risk. PMID- 27373279 TI - Taxonomic dissection of Achromobacter denitrificans Coenye et al. 2003 and proposal of Achromobacter agilis sp. nov., nom. rev., Achromobacter pestifer sp. nov., nom. rev., Achromobacter kerstersii sp. nov. and Achromobacter deleyi sp. nov. AB - The phenotypic and genotypic characteristics of a historical collection of strains identified as Achromobacter denitrificanswere examined. Sequence analysis of a 765 bp nrdA gene fragment revealed that eight of these strains belonged to the recently described Achromobacter aegrifaciens, Achromobacter mucicolens, and Achromobacter insolitus, and that one strain belonged to Achromobacter xylosoxidans. The analysis also suggested the presence of four novel species of the genus Achromobacter among the remaining strains. The latter was confirmed by multilocus sequence analysis of concatenated nusA, eno, rpoB, gltB, lepA, nuoL andnrdA gene fragments and extensive genotypic and phenotypic characterization. We propose to name these novel species as Achromobacter agilis sp. nov., nom. rev. (type strain LMG 3411T=CCUG 62454T), Achromobacter pestifer sp. nov., nom. rev. (type strain LMG 3431T=CCUG 61959T) , Achromobacter kerstersii sp. nov. (type strain LMG 3441T=CCUG 62449T) and Achromobacter deleyi sp. nov. (type strain LMG 3458T=CCUG 62433T). PMID- 27373280 TI - [The quality indicators of multiple inflammatory bowel disease centers in China should be consistent with the consensus]. PMID- 27373281 TI - [Enteral nutritional therapy in inflammatory bowel disease]. PMID- 27373282 TI - [Standardized training for resident and re-organization of general internal medicine]. PMID- 27373283 TI - [Clinical analysis of cutaneous manifestations and related factors in patients with ulcerative colitis]. AB - OBJECTIVE: To investigate the cutaneous manifestations in patients with ulcerative colitis (UC) and related factors. METHODS: Patients admitted to Department of Gastroenterology Peking University First Hospital from January 1994 to December 2014 and diagnosed as UC were retrospectively enrolled in this study. Skin disorders were confirmed by the dermatologists. Clinical data were collected and compared between patients with and without cutaneous manifestations. RESULTS: Among the total 373 UC patients, there were 34 cases (9.1%) with cutaneous manifestations, including 11 pyoderma gangrenosum, 8 erythema nodosum, 6 eczema, 3 psoriasis, 2 pemphigus, 1 granulomatous cheilitis, 1 ichthyosis, 1 acne rosacea, and 1 impetigo. The skin manifestations may occur after the diagnosis, simultaneously or even before the diagnosis of UC, which were 24, 7 and 3 patients respectively. The mean age in patients with skin lesions was (47.2+/ 12.1) years, male to female ratio 0.79?1. More patients with skin manifestations had severe activity of UC compared with non-skin group [50.0%(17/34) vs 25.1%(85/339), P=0.01]. In addition, the proportion of extensive colitis in skin lesion group was significantly higher than that in non-skin group [76.5%(26/34) vs 54.6%(185/339), P=0.04]. CONCLUSIONS: The cutaneous manifestations associated with UC are polymorphic, erythema nodosums and pyoderma gangrenosums are the most common skin lesions seen in UC patients. Skin lesions occur concurrently, pre or post the diagnosis of UC. Skin lesions in UC patients suggest more severe disease activity. Clinicians need to pay more attention to this group. PMID- 27373284 TI - [A comparison of clinical characteristics between non-erosive reflux disease and reflux esophagitis]. AB - OBJECTIVE: To summarize the clinical symptoms of patients with non-erosive reflux disease(NERD) and reflux esophagitis(RE), which is helpful to the differential diagnosis. METHODS: Out-patients who met the criteria of NERD or RE according to the Montreal definition in Gastroenterology Department Wuhan Union Hospital from 2010-2014 were enrolled in our study. Clinical data were comprehensively collected. Incidence of disease, severity, frequency of esophageal and extraesophageal symptoms, and the rates of overlapping with functional dyspepsia (FD) or irritable bowel syndrome (IBS) were all studied. RESULTS: Totally 446 subjects were recruited, including 225 patients with NERD and 221 patients with RE. The occurrence rates of esophageal symptoms including heartburn [76.0%(171/225) vs 52.0%(115/221), P<0.01] and acid regurgitation [74.7%(168/225) vs 54.3%(120/221), P<0.05] in NERD group were significantly higher than those in RE patients, with more severe and frequent (P<0.05). Despite the rates of food regurgitation were similar, NERD patients behaved more severely and frequently (P<0.05). Extraesophageal symptoms including throat burning and foreign body sensation in NERD group [40.9%(92/225) vs 27.6%(61/221), 42.2%(95/225) vs 31.7%(70/221), all P<0.05] were also higher than those in RE group, the degree of which was more severe too (P<0.05). RE patients claimed a higher proportion of chronic cough. The incidences of overlapping with IBS in two groups were similar. But there were more patients with FD in NERD group [72.0%(162/225) vs 62.9%(139/221), P<0.05] than in RE group. CONCLUSIONS: The menifestations and degree of esophageal and extraesophageal symptoms in patients with NERD or RE are different, as well as comorbidities such as FD and IBS. These results suggest that NERD and RE are independent diseases. PMID- 27373285 TI - [An analysis of clinical characteristics and factors in Parkinson's disease patients with excessive daytime sleepiness]. AB - OBJECTIVE: To explore the clinical characteristics and prognostic factors in patients with Parkinson's disease (PD) and excessive daytime sleepiness (EDS) and to identify whether EDS could influence the sleep architecture and sleep apnea related parameters. METHODS: A total of 130 PD patients were eligible and enrolled in the study.By the Epworth sleepiness scale (ESS), patients were divided into the EDS group (ESS>=10) with 61 patients and the non-EDS group (ESS<10) with 69 patients.All underwent a video-polysomnography (PSG). Clinical characteristics were mainly evaluated by the unified Parkinson's disease rating scale (UPDRS) and the Hoehn-Yahr(H-Y)stage.while other related scales were applied for evaluating depression, cognitive function, quality of sleep and quality of life. RESULTS: A total of 61 patients (46.92%) were diagnosed as EDS (ESS>=10). Compared to the non-EDS group, the EDS group had significantly higher score of HAMD, UPDRSIand UPDRSII, and significantly lower score of MoCA and PDQ (all P<0.05). Non-conditional logistic regression analysis showed that the scores of HAMD and UPDRSI were the main prognostic factors for EDS.Significantly decreased sleep latency (SL) was found in the EDS group by PSG (P=0.008). The score of ESS was showed to be correlated with the scores of HAMD, MoCA, UPDRSI, UPDRSII, PDQ and SL. CONCLUSIONS: PD patients with EDS have more severe depression and cognitive dysfunction and worse quality of life.Sleep structure is altered in those patients with decreased sleep latency.Mental status is closely associated with EDS, but not sleep apnea. PMID- 27373286 TI - [A comparison of the outcome of therapy between fractional flow reserve guided- versus coronary angiography guided-strategy in acute coronary syndrome patients with moderate coronary lesions]. AB - OBJECTIVE: To compare the outcomes between coronary angiography (CAG ) guided- and fractional flow reserve (FFR) guided-strategy in acute coronary syndrome (ACS) patients with moderate lesions. METHODS: Totally, 249 ACS subjects with moderate lesions examined by CAG in Beijing Anzhen Hospital from July 1, 2014 to July 30, 2015 were included in the present analysis. Among them, 98 patients were further examined by FFR and 151 were not. All the patients were treated with medication either guided by CAG or by FFR. Subjects were followed up for an average of 10 months. The end points included death, nonfatal myocardial infarction (MI), target vessel revascularization (TVR), and hospitalization costs. Major adverse cardiac events (MACE) were defined as death, nonfatal MI, and TVR. RESULTS: At the end of follow-up, 29 patients had MACE with 6 cases (6.5%) in the FFR-guided group, and 23 cases (16.2%) in the CAG-guided group (P=0.036). Patients treated with FFR-guided strategy had significantly lower rate of TVR than those treated with CAG-guided strategy (5.4% vs 14.8%, P=0.045). No statistical difference was observed in nonfatal MI (2.2% vs 3.5%, P=0.242) between the two groups, and no cardiac death occurred in the two groups. However, the rate of patients treated with stains (P=0.033) and the hospitalization costs (P=0.001) were significantly increased in the FFR-guided group. CONCLUSIONS: FFR guided strategy for patients with ACS results in lower TVR and MACE, but higher cost when compared with CAG-guided strategy. PMID- 27373287 TI - [The application of (18)F fluorodeoxyglucose-positron emission tomography/computed tomography in the diagnosis and treatment of dermatomyositis]. AB - OBJECTIVE: To investigate the value of (18)F fluorodeoxyglucose-positron emission tomography/computed tomography ((18)F FDG-PET-CT) in the diagnosis and the evaluation of disease activity and remission of dermatomyositis(DM). METHODS: DM patients who were admitted to the Department of Rheumatology, the People's Liberation Army General Hospital (PLAGH) and underwent (18)F FDG-PET-CT examination were retrospectively reviewed from January 2012 to May 2015.Gender and age matched healthy controls (HC) were also enrolled.The standardized uptake value (SUV) of proximal limb girdle muscles in both groups were recorded and compared, so as between patients with DM or subclinical DM.The correlation between myodynamia of proximal limb girdle muscle, creatine kinase(CK), CK-MB, serum ferritin and SUV of each muscle group were analyzed. RESULTS: There were 58 patients with DM and 29 controls consecutively recruited in the study.The SUV of upper arms (1.814+/-0.830) g/ml, shoulders (2.134+/-0.797) g/ml and hips (1.883+/ 0.683) g/ml in patients with classic DM were significantly higher than those with subclinical DM [(0.938+/-0.218) g/ml, (1.152+/-0.315) g/ml, (0.945+/-0.249) g/ml; P<0.05]. SUV of muscles in newly diagnosed patients was (1.051+/-0.031) g/ml, which was higher than that in subclinical patients.But the difference was not statistically significant (P>0.05). The average SUV of evaluated muscles in DM group (2.033+/-0.858) g/ml was significantly higher than that in controls (1.076+/-0.167) g/ml (P<0.001). Receiver operating characteristic(ROC) analysis revealed the area under the curve(AUC) of abnormal SUV detected by (18)F FDG-PET CT for diagnosing DM was 0.953.The myodynamia of upper arms and SUV was negatively correlated (rs=-0.440, P=0.031). However, the level of serum creatine kinase and SUV was positively correlated (rs=0.500, P=0.013). The average SUV of patients whose time to remission was less than 3 months (1.746+/-0.466) g/ml was obviously less than that of patients with 3 to 6 months to obtain remission (2.815+/-0.848) g/ml (P=0.015). CONCLUSIONS: The SUV of proximal limb girdle muscles detected by (18)F FDG-PET-CT has a positive diagnostic value for DM.Moreover, the SUV in upper arms is correlated with the muscle strength and the level of creatine kinase, which reflect disease activity. (18)F FDG-PET-CT might be an alternative method to evaluate the response of treatment. PMID- 27373288 TI - [The application of matrix metalloproteinase-3 and 7 joints ultrasonic score in assessment of disease activity in patients with rheumatoid arthritis]. AB - OBJECTIVE: To evaluate the significance of serum matrix metalloproteinase-3 (MMP 3) and joint ultrasonography in assessing the activity of rheumatoid arthritis (RA) by comparing MMP-3 level and the ultrasonic 7 joints (US7) score in RA patients. METHODS: Serum MMP-3 level and US7 score were measured in 133 RA patients by immune turbidity and Doppler ultrasound. Synchronous 53 healthy subjects were recruited as controls. Clinical data were collected. Erythrocyte sedimentation rate (ESR), serum level of anti-cyclic citrullinated peptide (CCP) antibody, health assessment questionnaire (HAQ) and disease activity score 28 (DAS28) were measured. The level of disease activity is interpreted as remission(DAS28<2.6), low(DAS 28>=2.6-<3.2), moderate(DAS 28>=3.2-<5.1), high(DAS28>=5.1). The discriminating validity of MMP-3 and US7 score in disease was evaluated using receiver operating characteristic (ROC) curve analysis with DAS28 as the reference standard. RESULTS: Compared with that in healthy controls [35.20(25.90, 48.90) MUg/L] and remission patients[33.40(22.60, 678.40) MUg/L], the MMP-3 level in moderate [105.1(61.70, 172.70) MUg/L] and high [363.1(161.50, 475.90) MUg/L] groups increased dramatically. US7 score in patients with high disease activity was significantly higher than that in other groups. The level of MMP-3 was significantly correlated with DAS28, HAQ, US7 score, yet did not have correlation with anti-CCP antibody. Serum level of MMP-3 was positively correlated with US7 score(r=0.566, P<0.001). In evaluating the disease activity, US7 score combined with MMP-3 (AUC 0.863 2) was not superior to MMP-3 alone (AUC 0.854 3), but significantly better than single US7 score (AUC 0.764 3, P<0.05). CONCLUSIONS: MMP-3 is an effective and simple index in evaluating RA disease activity. The combination of MMP-3 and US7 score does not further improve the efficacy to evaluate disease activity than MMP-3 alone in patients with RA. PMID- 27373289 TI - [A Meta-analysis of the accuracy of interferon-gamma release assays in differentiating intestinal tuberculosis from Crohn's disease in Asia]. AB - OBJECTIVE: This meta-analysis assessed the value of interferon-gamma release assays (IGRAs) in the differential diagnosis of intestinal tuberculosis (ITB) from Crohn's disease (CD). METHODS: Systematic search without language restriction was conducted in the main computerized databases until June 2015. Studies that have evaluated the performance of IGRAs (QuantiFERON-TB Gold or T SPOT.TB) in distinguishing ITB from CD were eligible. Main outcome measures included sensitivity and specificity. Area under the curve (AUC) of the summary receiver operating characteristic (sROC) curve was used to evaluate the accuracy of IGRAs. RESULTS: Twelve studies (all from Asia) were finally included. The pooled sensitivity and specificity of IGRAs for the differential diagnosis of ITB from CD were 82.8% (95%CI 78.4%-86.6%) and 86.7% (95%CI 83.2%-89.6%) respectively. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 6.870 (95%CI 5.345-8.830) and 0.171 (95%CI 0.105-0.279). The diagnostic odds ratio was 44.030 (95%CI 27.964-69.325). And the AUC of sROC was 0.939. CONCLUSIONS: IGRAs have a high sensitivity and specificity for the diagnosis of ITB, and specificity is consistent from study to study. IGRAs may be considered as a supplementary method in the differential diagnosis of ITB from CD. PMID- 27373290 TI - [The correlation study between the changes of intestinal mucosa predominant bacteria and Toll-like receptor 2, Toll-like receptor 4 gene expressions in diarrhea-predominant irritable bowel syndrome patients]. AB - Based on high throughput sequencing and PCR detection technology, this study has found out that intestinal microbial diversity was impaired and the quantities of two main bacteria flora (Bacteroidetes and Clostridium) were significantly reduced in patients with diarrhea-predominant irritable bowel syndrome (D-IBS). Meanwhile mucosal expression of toll-like receptor (TLR) 2 and TLR4 were significantly enhanced, which was inversely correlated with the reduction of Bacteroidetes and Clostridium. Thus, it suggests that D-IBS may be associated with TLR signal transduction triggered by the intestinal dysbacteriosis. PMID- 27373291 TI - [A clinical analysis of insulin antibody in type 2 diabetic patients]. AB - This study was conducted to evaluate the relationship between serum insulin levels and the production of insulin antibody (IA) in type 2 diabetes (T2DM). A total of 647 T2DM were included. Among them, 20.9% patients were IA positive, who were elder and had a longer duration, lower BMI, a higher positive rate of glutamic acid decarboxylase antibody(GADAb) and higher serum insulin levels during an insulin secretion test. More patients were treated with insulin in IA positive group than in IA negative group (65.9% vs 41.0%, P=0.000). Fasting serum insulin level was associated with occurrence of IA in all patients (OR=1.02, P=0.001) and insulin treated patients (OR=1.033, P=0.002). The cut-off point of fasting serum insulin level for predicting IA positive was 17.87 mIU/L (sensitivity 55.1%, specificity 89.0%). Exogenous insulin use is associated with the presence of IA. Fasting serum insulin level can be used as a predictor for the production of IA in insulin-treated patients. PMID- 27373292 TI - [A case of mesenteric panniculitis]. PMID- 27373293 TI - [A case report of POEMS syndrome with multiple endocrine abnormalities as the main manifestations]. PMID- 27373294 TI - [A case of fibrocalculous pancreatic diabetes]. PMID- 27373295 TI - [The management model of endocrine and metabolic diseases in the minorities of the border areas]. PMID- 27373296 TI - [Esophageal dysmotility of eosinophilic esophagitis]. PMID- 27373297 TI - [An update of rituximab treatment in idiopathic membranous nephropathy]. PMID- 27373298 TI - [The mechanism of innate immune response to Acinetobacter baumannii infection]. PMID- 27373299 TI - [The Chinese expert recommendation on prevention of gastrointestinal injury related to antithrombotic therapy]. PMID- 27373300 TI - [The Chinese Delphi consensus on quality indicators for inflammatory bowel disease centers]. PMID- 27373301 TI - [The Chinese expert consensus on reteplase thrombolytic therapy for acute ST segment elevation myocardial infarction]. PMID- 27373302 TI - [The 451(th) case: intermittent rash, fever and headache]. AB - A 29-year-old woman was admitted to the Department of Rheumatology, Peking Union Medical College Hospital due to intermittent rashes, fever and headache. Palpable purpura were symmetrically distributed on the extremities and trunk. Other manifestations included headache with nausea and vomiting. Elevated white blood cell (WBC) count, platelet (PLT) count, erythrocyte sedimentation rate (ESR) and C-reactive protein were the main laboratory findings. Antinuclear antibodies and antineutrophil cytoplasmic antibodies were negative. Examination of the cerebrospinal fluid (CSF) revealed high intracranial pressure, while routine cytology and biochemical tests of CSF were normal. Head MRI scan and PET-CT did not detect remarkable findings. A diagnosis of systemic vasculitis was confirmed by the biopsy of skin lesion which showed inflammatory infiltration of the muscular vessel wall. Combination therapy of corticosteroids and cyclophosphamide lead to a rapid improvement in clinical symptoms and laboratory parameters. The patient was in stable remission till 6 month follow-up. PMID- 27373304 TI - ER/LA Opioid Analgesics REMS: Overview of Ongoing Assessments of Its Progress and Its Impact on Health Outcomes. AB - Objective: Opioid abuse is a serious public health concern. In response, the Food and Drug Administration (FDA) determined that a risk evaluation and mitigation strategy (REMS) for extended-release and long-acting (ER/LA) opioids was necessary to ensure that the benefits of these analgesics continue to outweigh the risks. Key components of the REMS are training for prescribers through accredited continuing education (CE), and providing patient educational materials. Methods: The impact of this REMS has been assessed using diverse metrics including evaluation of prescriber and patient understanding of the risks associated with opioids; patient receipt and comprehension of the medication guide and patient counseling document; patient satisfaction with access to opioids; drug utilization and changes in prescribing patterns; and surveillance of ER/LA opioid misuse, abuse, overdose, addiction, and death. Results and Conclusions: The results of these assessments indicate that the increasing rates of opioid abuse, addiction, overdose, and death observed prior to implementation of the REMS have since leveled off or started to decline. However, these benefits cannot be attributed solely to the ER/LA opioid analgesics REMS since many other initiatives to prevent abuse occurred contemporaneously. These improvements occurred while preserving patient access to opioids as a large majority of patients surveyed expressed satisfaction with their access to opioids. PMID- 27373305 TI - Layer-Controlled Chemical Vapor Deposition Growth of MoS2 Vertical Heterostructures via van der Waals Epitaxy. AB - The fascinating semiconducting and optical properties of monolayer and few-layer transition metal dichalcogenides, as exemplified by MoS2, have made them promising candidates for optoelectronic applications. Controllable growth of heterostructures based on these layered materials is critical for their successful device applications. Here, we report a direct low temperature chemical vapor deposition (CVD) synthesis of MoS2 monolayer/multilayer vertical heterostructures with layer-controlled growth on a variety of layered materials (SnS2, TaS2, and graphene) via van der Waals epitaxy. Through precise control of the partial pressures of the MoCl5 and elemental sulfur precursors, reaction temperatures, and careful tracking of the ambient humidity, we have successfully and reproducibly grown MoS2 vertical heterostructures from 1 to 6 layers over a large area. The monolayer MoS2 heterostructure was verified using cross-sectional high resolution transmission electron microscopy (HRTEM) while Raman and photoluminescence spectroscopy confirmed the layer-controlled MoS2 growth and heterostructure electronic interactions. Raman, photoluminescence, and energy dispersive X-ray spectroscopy (EDS) mappings verified the uniform coverage of the MoS2 layers. This reaction provides an ideal method for the scalable layer controlled growth of transition metal dichalcogenide heterostructures via van der Waals epitaxy for a variety of optoelectronic applications. PMID- 27373306 TI - Modeling Ti/Ge Distribution in LiTi2-xGex(PO4)3 NASICON Series by (31)P MAS NMR and First-Principles DFT Calculations. AB - Ti/Ge distribution in rhombohedral LiTi2-xGex(PO4)3 NASICON series has been analyzed by (31)P magic-angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy and first-principles density functional theory (DFT) calculations. Nuclear magnetic resonance is an excellent probe to follow Ti/Ge disorder, as it is sensitive to the atomic scale environment without long-range periodicity requirements. In the samples considered here, PO4 units are surrounded by four Ti/Ge octahedra, and then, five different components ascribed to P(OTi)4, P(OTi)3(OGe), P(OTi)2(OGe)2, P(OTi)(OGe)3, and P(OGe)4 environments are expected in (31)P MAS NMR spectra of R3c NASICON samples. However, (31)P MAS NMR spectra of analyzed series display a higher number of signals, suggesting that, although the overall symmetry remains R3c, partial substitution causes a local decrement in symmetry. With the aid of first-principles DFT calculations, 10 detected (31)P NMR signals have been assigned to different Ti4-nGen arrangements in the R3 subgroup symmetry. In this assignment, the influence of octahedra of the same or different R2(PO4)3 structural units has been considered. The influence of bond distances, angles and atom charges on (31)P NMR chemical shieldings has been discussed. Simulation of the LiTi2-xGex(PO4)3 series suggests that detection of 10 P environments is mainly due to the existence of two oxygen types, O1 and O2, whose charges are differently affected by Ge and Ti occupation of octahedra. From the quantitative analysis of detected components, a random Ti/Ge distribution has been deduced in next nearest neighbor (NNN) sites that surround tetrahedral PO4 units. This random distribution was supported by XRD data displaying Vegard's law. PMID- 27373308 TI - Nucleotide diversity, natural variation, and evolution of Flexible culm-1 and Strong culm-2 lodging resistance genes in rice. AB - Lodging resistance is one of the vital traits in yield improvement and sustainability. Culm wall thickness, diameter, and strength are different traits that can govern the lodging resistance in rice. The genes SCM2 and FC1 have been isolated for culm thickness, strength, and flexibility, but their functional nucleotide variations were still unknown. We used a 13* deep sequence of 795 diverse genotypes to present the functional variation and SNP diversity in SCM2 and FC1. The major functional variant for the SCM2 gene was at position 27480181 and for the FC1 gene at position 31072992. Haplotype analysis of both genes provided their various allelic differences among haplotypes. SCM2 alleles further presented the evolution of Oryza sativa L. subsp. indica and subsp. japonica genomes from common parent in different geographical zones, while the haplotypes of FC1 suggested their evolution from different strains of the common parent Oryza rufipogon. SCM2 showed purifying selection and functional associations with rare alleles, while FC1 displayed balanced selection favored by multiple heterozygous alleles. Genotypes with an allelic combination of SCM2-3 and FC1-2 in japonica background exhibited striking resistance against lodging, which can be used in further breeding programs. PMID- 27373309 TI - A case of human papillomavirus-associated squamous cell carcinoma with bone invasion and verruca vulgaris of the fingernails. PMID- 27373307 TI - Identification of the genomic mutation in Epha4(rb-2J/rb-2J) mice. AB - The EphA4 receptor tyrosine kinase is involved in numerous cell-signalling activities during embryonic development. EphA4 has the ability to bind to both types of ephrin ligands, the ephrinAs and ephrinBs. The C57BL/6J-Epha4rb-2J/GrsrJ strain, denoted Epha4(rb-2J/rb-2J), is a spontaneous mouse mutant that arose at The Jackson Laboratory. These mutants exhibited a synchronous hind limb locomotion defect or "hopping gait" phenotype, which is also characteristic of EphA4 null mice. Genetic complementation experiments suggested that Epha4(rb-2J) corresponds to an allele of EphA4, but details of the genomic defect in this mouse mutant are currently unavailable. We found a single base-pair deletion in exon 9 resulting in a frame shift mutation that subsequently resulted in a premature stop codon. Analysis of the predicted structure of the truncated protein suggests that both the kinase and sterile alpha motif (SAM) domains are absent. Definitive determination of genotype is needed for experimental studies of mice carrying the Epha4(rb-2J) allele, and we have also developed a method to ease detection of the mutation through RFLP. Eph-ephrin family members are reportedly expressed as numerous isoforms. Hence, delineation of the specific mutation in EphA4 in this strain is important for further functional studies, such as protein-protein interactions, immunostaining and gene compensatory studies, investigating the mechanism underlying the effects of altered function of Eph family of receptor tyrosine kinases on phenotype. PMID- 27373310 TI - Etude Par Ponction Tracheale De La Flore Bacterienne Des Pneumopathies Infectieuses. AB - The authors analyse the bacteriological data gathered by 100 successive tracheal Punctures and compare these results to those obtained by sputum cultures, which had either been collected by routine or when withdrawing the catheter for tracheal aspiration. This plain and not hazardous technique allows to draw the following conclusions : 1) The culture of routinely collected sputum at the patient's bed-side often misleads the physician (6 times on 10) whereas newly expectorated sputum brought immediately to the laboratory more truly shows the tracheo-bronchic flora (valuable results in 75 % of the cases). 2) The tracheal puncture, which reduces the causes of errors, due to the contamination of the sputum by the rhino-pharyngeal flora, to a minimum, particularly is indicated in the following cases : patients who do not expectorate (including suspects of pulmonary tuberculosis), instantly earnest pneumopathia, bad response to applied antibiotic therapy, tests of the true efficiency of an antibiotic therapy. 3) The bacteriological study of these punctures performed on patients, who caused therapeutical problems and who had been submitted to antibiotic therapies evidenced the following data : 40 % of the punctures were sterile, 39 % showed one single germ (18 Gram negative, 16 Gram positive, 2 BK, 3 aspergillus), 15 % showed 2 simultaneous germs and 6 % were not significant. PMID- 27373311 TI - Essai de L'Association Trimethoprim-Sulfamethoxazole dans les Infections Broncho Pulmonaires. AB - The authors studied the effectiveness of a compound drug, sulphamethoxazole trimethoprim, in acute pulmonary disease of moderate gravity. :They reviewed the numerous criteria used in medical papers during clinical trials concerning antibiotics. They emphasized the value of transtracheal aspiration for the correct interpretation of the bacteriological flora in the tracheo-bronchial tree. The treatment was effective in 24 cases (19 good and 5 fair) over 31 (70 %). No toxic reaction was noted during this short term trial. PMID- 27373313 TI - Virtual screening, molecular dynamics, and binding free energy calculations on human carbonic anhydrase IX catalytic domain for deciphering potential leads. AB - Carbonic anhydrase IX is a tumor-associated membrane-bound metallo-enzyme which catalyzes the reversible hydration of carbon dioxide (CO2) to bicarbonate (HCO3-) and proton (H+) ions. It is a hypoxia-inducible enzyme and plays a critical role in tumor pH homeostasis favoring tumor cell invasiveness and drug resistance. Over expression of CAIX is documented in cancers of breast, lung, kidney, colon/rectum, etc. Chemical inhibition of CAIX activity has proven to be an effective therapeutic modality towards targeting cancer. Hence, in this study, we intend to identify potential molecules from NCI (National Cancer Institute) and Maybridge databases implementing high-throughput virtual screening. CAIX co crystallized with acetazolamide (a known inhibitor of CAIX) (PDB ID: 3IAI) was used for reference-guided docking protocol. The potential inhibitors among the coupled data sets were finalized based on Glide docking score, Prime/MMGBSA scoring, significant intermolecular interactions, ADMET (absorption, distribution, metabolism and excretion, toxicity) prediction and stability of complex formation, molecular dynamics simulation, and comparative analysis. By this study, we propose NSC_93618, NSC_170253, NSC_93618, JFD03677, SEW06488, and BTB09372 to be highly significant, as all these compounds were found to qualify as potential leads surpassing all the stringent filtering process. However, NSC_93618 was found to be the most potential, as it featured with higher complex stability with strong bonded interactions, binding affinity synonymous to acetazolamide. Hence, these proposed compounds shall prove to be effective in targeting CAIX towards modulating carcinogenesis. PMID- 27373314 TI - Promotion of epithelial-mesenchymal transition by Frizzled2 is involved in the metastasis of endometrial cancer. AB - The Wnt signaling pathway is essential for embryonic development, and genetic alteration in this network is closely correlated with tumorigenesis and progression. Previous research has shown that Wnt receptor Frizzled2 (Fzd2) is elevated in many metastatic cancer cell lines and high grade tumors. Yet, little is known about the Fzd2 expression and activity in human endometrial cancer (EC). In this study, we present evidence of a direct role of Fzd2 in human EC. We found that Fzd2 expression was higher in EC than that in adjacent normal tissues, and was correlated with epithelial-mesenchymal transition markers. Next, it was determined that the stable overexpression of Fzd2 in HEC-1B and Ishikawa cells promoted cell migration and induced an EMT phenotype. Conversely, RNA interference-mediated depletion of Fzd2 inhibited EC cell migration. Additionally, mechanistic investigation revealed that elevated Fzd2 expression activated canonical Wnt signaling and was blocked by canonical Wnt signaling inhibitor XAV939. However, Fzd2 did not influence the proliferation of EC cells. Thus, Fzd2 may be a potential marker for EC metastasis and a target for future therapies for this disease. PMID- 27373315 TI - Riemerella anatipestifer infection in domestic ducks in Japan, 2014. AB - The outbreak of Riemerella anatipestifer (RA) infection has been confirmed in meat-type domestic ducks (Anas platyrhynchos) for the first time in 27 years in Japan. In January 2014, increased mortality in a 14- to 21-day-old duck flock was reported to veterinary officials by the owner. The affected ducks exhibited reduced movement, ataxia and dorsal recumbency with leg paddling. Pathological findings were typical for an RA infection. Fibrinous and heterophilic pericarditis, airsacculitis, perihepatitis, ventriculitis and meningitis were observed. The bacterial isolate from duck organs was identified as RA by PCR based 16S ribosomal RNA sequencing. PMID- 27373316 TI - COL11A1 is overexpressed in recurrent non-small cell lung cancer and promotes cell proliferation, migration, invasion and drug resistance. AB - Collagen type XI alpha1 (COL11A1), a minor fibrillar collagen, has been demonstrated to be involved in cell proliferation, migration and the tumorigenesis of many human malignancies. Previous studies have shown that COL11A1 may be a valuable diagnostic marker for non-small cell lung carcinoma (NSCLC). However, its biological function in NSCLC progression remains largely unclear. In the present study, we investigated the expression levels of COL11A1 in different human NSCLC samples, and found that COL11A1 was overexpressed in NSCLC with lymph node metastasis and in recurrent NSCLC tissues. We also revealed that COL11A1 promoted the cell proliferation, migration and invasion of NSCLC cell lines in vitro. Furthermore, our results highlighted the importance of COL11A1 in chemoresistance to cisplatin. Mechanistically, we found that the effects of the overexpression of COL11A1 in NSCLC cells were mediated by Smad signaling. Collectively, our findings suggest that COL11A1 may sever as a biomarker for metastatic NSCLC, and can be used to predict recurrence after surgical resection. Therapeutic approaches targeting COL11A1 may facilitate the optimization of cisplatin treatment of NSCLC by overcoming chemoresistance. PMID- 27373317 TI - Management of impulse control disorders in Parkinson's disease. AB - BACKGROUND: Impulse control disorders (ICDs) have become a widely recognized non motor complication of Parkinson's disease (PD) in patients taking dopamine replacement therapy (DRT). There are no current evidence-based recommendations for their treatment, other than reducing their dopaminergic medication. METHODS: This study reviews the current literature of the treatment of ICDs including pharmacological treatments, deep brain stimulation, and psychotherapeutic interventions. RESULTS: Dopamine agonist withdrawal is the most common and effective treatment, but may lead to an aversive withdrawal syndrome or motor symptom degeneration in some individuals. There is insufficient evidence for all other pharmacological treatments in treating ICDs in PD, including amantadine, serotonin selective reuptake inhibitors, antipsychotics, anticonvulsants, and opioid antagonists (e.g. naltrexone). Large randomized control trials need to be performed before these drugs can be routinely used for the treatment of ICDs in PD. Deep brain stimulation remains equivocal because ICD symptoms resolve in some patients after surgery but may appear de novo in others. Cognitive behavioral therapy has been shown to improve ICD symptoms in the only published study, although further research is urgently needed. CONCLUSIONS: Further research will allow for the development of evidence-based guidelines for the management of ICDs in PD. PMID- 27373318 TI - The bright side of psychoactive substances: cannabinoid-based drugs in motor diseases. AB - INTRODUCTION: Psychoactive substances are associated with the idea of drugs with high addictive liability, affecting mental states, cognition, emotion and motor behavior. However these substances can modify synaptic transmission and help to disclose some mechanisms underlying alterations in brain processing and pathophysiology of motor disease. Hence, the 'bright side' of e cannabinoid-based drugs must be thoroughly examined to be identified within the latter framework. AREAS COVERED: We will analyze the preclinical and clinical evidence of cannabinoid-based drugs, discussing their therapeutic value in basal ganglia motor disorders such as Parkinson's disease and Huntington disease. Expert commentary: Despite the knowledge acquired in the last years, the therapeutic potential of cannabinoid-based drugs should be further tested by novel routes of investigation. This should be focused on the role of cannabinoid signaling system in mitochondrial function as well as on the physical and functional interaction with other key receptorial targets belonging to this network. PMID- 27373319 TI - Isolation of a new beta-carboline alkaloid from aerial parts of Triclisia sacleuxii and its antibacterial and cytotoxicity effects. AB - A new beta-carboline alkaloid named sacleuximine A (1) together with known compounds palmatine (2), isotetrandrine (3), trans-N-feruloyltyramine (4), trans N-caffeoyltyramine (5), yangambin (6), syringaresinol (7), sesamin (8), (+) epi quercitol (9), 4-hydroxybenzaldehyde (10), beta-sitosterol (11), quercetin 3-O rutinoside (12) and myricetin 3-O-beta-glucose (1->6) alpha-rhamnoside (13) have been isolated from methanol extract of Triclisia sacleuxii aerial parts. Compounds 1-10 were evaluated for their cytotoxicity against human adenocarcinoma (HeLa), human hepatocarcinoma (Hep3B) and human breast carcinoma (MCF-7) cells lines and also for antibacterial activities against both Gram-positive and Gram negative bacteria. The cytotoxicity (IC50) values ranged between 0.15 and 36.7 MUM while the minimum inhibitory concentrations were found to be in the range of 3.9 and 125 MUM, respectively. This is the first report of antibacterial compounds and the isolation of lignans together with a beta-carboline alkaloid from T. sacleuxii. PMID- 27373320 TI - An Open and Shut Case: The Interaction of Magnesium with MST Enzymes. AB - The shikimate pathway of bacteria, fungi, and plants generates chorismate, which is drawn into biosynthetic pathways that form aromatic amino acids and other important metabolites, including folates, menaquinone, and siderophores. Many of the pathways initiated at this branch point transform chorismate using an MST enzyme. The MST enzymes (menaquinone, siderophore, and tryptophan biosynthetic enzymes) are structurally homologous and magnesium-dependent, and all perform similar chemical permutations to chorismate by nucleophilic addition (hydroxyl or amine) at the 2-position of the ring, inducing displacement of the 4-hydroxyl. The isomerase enzymes release isochorismate or aminodeoxychorismate as the product, while the synthase enzymes also have lyase activity that displaces pyruvate to form either salicylate or anthranilate. This has led to the hypothesis that the isomerase and lyase activities performed by the MST enzymes are functionally conserved. Here we have developed tailored pre-steady-state approaches to establish the kinetic mechanisms of the isochorismate and salicylate synthase enzymes of siderophore biosynthesis. Our data are centered on the role of magnesium ions, which inhibit the isochorismate synthase enzymes but not the salicylate synthase enzymes. Prior structural data have suggested that binding of the metal ion occludes access or egress of substrates. Our kinetic data indicate that for the production of isochorismate, a high magnesium ion concentration suppresses the rate of release of product, accounting for the observed inhibition and establishing the basis of the ordered-addition kinetic mechanism. Moreover, we show that isochorismate is channeled through the synthase reaction as an intermediate that is retained in the active site by the magnesium ion. Indeed, the lyase-active enzyme has 3 orders of magnitude higher affinity for the isochorismate complex relative to the chorismate complex. Apparent negative-feedback inhibition by ferrous ions is documented at nanomolar concentrations, which is a potentially physiologically relevant mode of regulation for siderophore biosynthesis in vivo. PMID- 27373321 TI - The role of the inflammasome in patients with autoinflammatory diseases. AB - Autoinflammatory diseases are disorders of the innate immune system, characterized by systemic inflammation often driven by inflammasomes, and independent of infection and autoreactive antibodies or antigen-specific T cells. These diseases are increasingly recognized as disorders of immune dysregulation, presenting with a constellation of fevers, rashes, and mucosal symptoms in many cases, which suggests that the allergist/immunologist is the appropriate specialist for these patients. However, many practicing physicians are unaware of these disorders in their pediatric and adult patient populations, leading to substantial delays in diagnosis. Recognizing autoinflammatory disease symptom patterns, performing appropriate diagnostic tests, and instituting early effective therapy are essential to reduce morbidity and mortality in these patients. This review will focus on understanding the molecular basis of inflammasomes, recognizing the distinguishing features of the classic autoinflammatory disorders, and appreciating the treatment modalities available. PMID- 27373322 TI - Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation affecting predominantly the lung parenchyma and peripheral airways that results in largely irreversible and progressive airflow limitation. This inflammation is characterized by increased numbers of alveolar macrophages, neutrophils, T lymphocytes (predominantly TC1, TH1, and TH17 cells), and innate lymphoid cells recruited from the circulation. These cells and structural cells, including epithelial and endothelial cells and fibroblasts, secrete a variety of proinflammatory mediators, including cytokines, chemokines, growth factors, and lipid mediators. Although most patients with COPD have a predominantly neutrophilic inflammation, some have an increase in eosinophil counts, which might be orchestrated by TH2 cells and type 2 innate lymphoid cells though release of IL-33 from epithelial cells. These patients might be more responsive to corticosteroids and bronchodilators. Oxidative stress plays a key role in driving COPD-related inflammation, even in ex-smokers, and might result in activation of the proinflammatory transcription factor nuclear factor kappaB (NF kappaB), impaired antiprotease defenses, DNA damage, cellular senescence, autoantibody generation, and corticosteroid resistance though inactivation of histone deacetylase 2. Systemic inflammation is also found in patients with COPD and can worsen comorbidities, such as cardiovascular diseases, diabetes, and osteoporosis. Accelerated aging in the lungs of patients with COPD can also generate inflammatory protein release from senescent cells in the lung. In the future, it will be important to recognize phenotypes of patients with optimal responses to more specific therapies, and development of biomarkers that identify the therapeutic phenotypes will be important. PMID- 27373323 TI - Regulation of inflammasomes by autophagy. AB - Inflammasomes detect pathogen-associated molecular patterns to induce inflammatory innate immune responses and play a key role in host defense against infectious agents. However, inflammasomes are often wrongly activated by metabolites, amyloids, and environmental irritants. This induces massive inflammation, causing severe tissue damage, and results in the development of inflammatory diseases. Hence cellular machineries regulating both "activation" and "inactivation" of inflammasomes are definitely important. Recent studies have shown that autophagy, an intracellular degradation system associated with maintenance of cellular homeostasis, plays a key role in inflammasome inactivation. Notably, autophagy deficiency caused by gene mutation disrupts organelle elimination and thus induces aberrant activation of inflammasomes, leading to severe tissue damage. Here we review recent findings regarding the involvement of autophagy in the regulation of inflammasome activation and development of inflammatory disorders. PMID- 27373324 TI - Interferons and inflammasomes: Cooperation and counterregulation in disease. AB - Interferons and the IL-1 family of cytokines have important roles in host defense against invading viruses and bacteria. Inflammasomes, multimeric cytosolic sensors of infection, are required for IL-1beta and IL-18 processing and release. Interferons, IL-1beta, and IL-18 are also implicated in autoimmune disease and chronic inflammation. Although independent but complementary pathways induce these cytokine subsets during infection, in some circumstances the cross-talk between these key inflammatory mediators is a particular requirement for effective host defense. In this review we will summarize recent discoveries concerning the potentiation of inflammasome responses by type I interferons, particularly in patients with gram-negative bacterial infections, and reflect on the molecular mechanisms of IFN-beta's immunosuppressive effects through modulation of inflammasome and IL-1beta signaling in patients with tuberculosis and multiple sclerosis. PMID- 27373326 TI - United Nations Climate Change Conferences: COP21 a lost opportunity for asthma and allergies and preparing for COP22. PMID- 27373325 TI - Current concepts in chronic inflammatory diseases: Interactions between microbes, cellular metabolism, and inflammation. AB - Recent research indicates that chronic inflammatory diseases, including allergies and autoimmune and neuropsychiatric diseases, share common pathways of cellular and molecular dysregulation. It was the aim of the International von-Behring Rontgen Symposium (October 16-18, 2014, in Marburg, Germany) to discuss recent developments in this field. These include a concept of biodiversity; the contribution of urbanization, lifestyle factors, and nutrition (eg, vitamin D); and new mechanisms of metabolic and immune dysregulation, such as extracellular and intracellular RNAs and cellular and mitochondrial stress. Epigenetic mechanisms contribute further to altered gene expression and therefore to the development of chronic inflammation. These novel findings provide the foundation for further development of preventive and therapeutic strategies. PMID- 27373328 TI - The safety of intranasal steroids during pregnancy: A good start. PMID- 27373330 TI - Correction. PMID- 27373331 TI - Correction. PMID- 27373329 TI - Efficacy of 2 months of allergen-specific immunotherapy with Bet v 1-derived contiguous overlapping peptides in patients with allergic rhinoconjunctivitis: Results of a phase IIb study. AB - BACKGROUND: An immunotherapy formulation consisting of 3 contiguous overlapping peptides (COPs) derived from Bet v 1, the major birch pollen allergen, showed good clinical tolerability in a previous phase I/IIa clinical trial. OBJECTIVES: We sought to evaluate the efficacy and safety of allergen-specific immunotherapy using 2 dose regimens of Bet v 1 COPs versus placebo in subjects with birch pollen-induced allergic rhinoconjunctivitis. METHODS: A randomized, double-blind, placebo-controlled phase IIb clinical trial was performed to assess the efficacy of Bet v 1 COP immunotherapy during the 2013 birch pollen season. Before the season, Bet v 1 COPs (50 and 100 MUg in aluminum hydroxide) or placebo (saline and aluminum hydroxide) were administered as 5 subcutaneous injections to 239 adults with allergic rhinoconjunctivitis to birch pollen. Bet v 1 COPs at 25 or 50 MUg were administered on day 1, and 50 or 100 MUg was administered on days 8, 15, 29, and 57, respectively. Patients were monitored for adverse events during the treatment period and assessed for combined rhinoconjunctivitis symptom and medication scores, as well as quality of life. RESULTS: Rhinoconjunctivitis symptom and medication scores improved in both Bet v 1 COP-treated groups, reaching statistical significance over placebo in the 50-MUg group (least squares mean, -0.23; 26% improvement; P = .015). Both active groups showed significant improvement in quality of life and nighttime nasal symptom scores, supporting the primary end point findings. Bet v 1 COP injections were well tolerated, with a higher frequency of systemic adverse events in the 100-MUg group. CONCLUSION: Two months of preseasonal immunotherapy with 3 COPs derived from Bet v 1 at a 50-MUg dose showed promising efficacy, small risk for systemic reactions, and immunomodulatory changes in this single-season, dose-finding, phase IIb trial in patients allergic to birch pollen. PMID- 27373332 TI - Prevalent, Dynamic, and Conserved R-Loop Structures Associate with Specific Epigenomic Signatures in Mammals. AB - R-loops are three-stranded nucleic acid structures formed upon annealing of an RNA strand to one strand of duplex DNA. We profiled R-loops using a high resolution, strand-specific methodology in human and mouse cell types. R-loops are prevalent, collectively occupying up to 5% of mammalian genomes. R-loop formation occurs over conserved genic hotspots such as promoter and terminator regions of poly(A)-dependent genes. In most cases, R-loops occur co transcriptionally and undergo dynamic turnover. Detailed epigenomic profiling revealed that R-loops associate with specific chromatin signatures. At promoters, R-loops associate with a hyper-accessible state characteristic of unmethylated CpG island promoters. By contrast, terminal R-loops associate with an enhancer- and insulator-like state and define a broad class of transcription terminators. Together, this suggests that the retention of nascent RNA transcripts at their site of expression represents an abundant, dynamic, and programmed component of the mammalian chromatin that affects chromatin patterning and the control of gene expression. PMID- 27373333 TI - Structure of a Complete ATP Synthase Dimer Reveals the Molecular Basis of Inner Mitochondrial Membrane Morphology. AB - We determined the structure of a complete, dimeric F1Fo-ATP synthase from yeast Yarrowia lipolytica mitochondria by a combination of cryo-EM and X-ray crystallography. The final structure resolves 58 of the 60 dimer subunits. Horizontal helices of subunit a in Fo wrap around the c-ring rotor, and a total of six vertical helices assigned to subunits a, b, f, i, and 8 span the membrane. Subunit 8 (A6L in human) is an evolutionary derivative of the bacterial b subunit. On the lumenal membrane surface, subunit f establishes direct contact between the two monomers. Comparison with a cryo-EM map of the F1Fo monomer identifies subunits e and g at the lateral dimer interface. They do not form dimer contacts but enable dimer formation by inducing a strong membrane curvature of ~100 degrees . Our structure explains the structural basis of cristae formation in mitochondria, a landmark signature of eukaryotic cell morphology. PMID- 27373335 TI - eIF3 Peripheral Subunits Rearrangement after mRNA Binding and Start-Codon Recognition. AB - mRNA translation initiation in eukaryotes requires the cooperation of a dozen eukaryotic initiation factors (eIFs) forming several complexes, which leads to mRNA attachment to the small ribosomal 40S subunit, mRNA scanning for start codon, and accommodation of initiator tRNA at the 40S P site. eIF3, composed of 13 subunits, 8 core (a, c, e, f, h, l, k, and m) and 5 peripheral (b, d, g, i, and j), plays a central role during this process. Here we report a cryo-electron microscopy structure of a mammalian 48S initiation complex at 5.8 A resolution. It shows the relocation of subunits eIF3i and eIF3g to the 40S intersubunit face on the GTPase binding site, at a late stage in initiation. On the basis of a previous study, we demonstrate the relocation of eIF3b to the 40S intersubunit face, binding below the eIF2-Met-tRNAi(Met) ternary complex upon mRNA attachment. Our analysis reveals the deep rearrangement of eIF3 and unravels the molecular mechanism underlying eIF3 function in mRNA scanning and timing of ribosomal subunit joining. PMID- 27373334 TI - BRCA1/FANCD2/BRG1-Driven DNA Repair Stabilizes the Differentiation State of Human Mammary Epithelial Cells. AB - An abnormal differentiation state is common in BRCA1-deficient mammary epithelial cells, but the underlying mechanism is unclear. Here, we report a convergence between DNA repair and normal, cultured human mammary epithelial (HME) cell differentiation. Surprisingly, depleting BRCA1 or FANCD2 (Fanconi anemia [FA] proteins) or BRG1, a mSWI/SNF subunit, caused HME cells to undergo spontaneous epithelial-to-mesenchymal transition (EMT) and aberrant differentiation. This also occurred when wild-type HMEs were exposed to chemicals that generate DNA interstrand crosslinks (repaired by FA proteins), but not in response to double strand breaks. Suppressed expression of DeltaNP63 also occurred in each of these settings, an effect that links DNA damage to the aberrant differentiation outcome. Taken together with somatic breast cancer genome data, these results point to a breakdown in a BRCA/FA-mSWI/SNF-DeltaNP63-mediated DNA repair and differentiation maintenance process in mammary epithelial cells that may contribute to sporadic breast cancer development. PMID- 27373336 TI - Allosteric Activation of Ubiquitin-Specific Proteases by beta-Propeller Proteins UAF1 and WDR20. AB - Ubiquitin-specific proteases (USPs) constitute the largest family of deubiquitinating enzymes, whose catalytic competency is often modulated by their binding partners through unknown mechanisms. Here we report on a series of crystallographic and biochemical analyses of an evolutionarily conserved deubiquitinase, USP12, which is activated by two beta-propeller proteins, UAF1 and WDR20. Our structures reveal that UAF1 and WDR20 interact with USP12 at two distinct sites far from its catalytic center. Without increasing the substrate affinity of USP12, the two beta-propeller proteins potentiate the enzyme through different allosteric mechanisms. UAF1 docks at the distal end of the USP12 Fingers domain and induces a cascade of structural changes that reach a critical ubiquitin-contacting loop adjacent to the catalytic cleft. By contrast, WDR20 anchors at the base of this loop and remotely modulates the catalytic center of the enzyme. Our results provide a mechanistic example for allosteric activation of USPs by their regulatory partners. PMID- 27373338 TI - Maximising fitness in the face of parasites: a review of host tolerance. AB - Tolerance, the ability of a host to limit the negative fitness effects of a given parasite load, is now recognised as an important host defence strategy in animals. Together with resistance, the ability of a host to limit parasite load, these two host strategies represent two disparate host responses to parasites, each with different predicted evolutionary consequences: resistance is predicted to reduce parasite prevalence, whereas tolerance could be neutral towards, or increase, parasite prevalence in a population. The distinction between these two strategies might have far-reaching epidemiological consequences. Classically, a reaction norm defines host tolerance because it depicts the change in host fitness as a function of parasite load, where a shallow negative slope indicates that host fitness slowly deteriorates as parasite load increases (i.e., high tolerance). Despite the fact that tolerance was only recently acknowledged to be an important component in an animal's immune repertoire, it is frequently referenced, so our aim is to emphasise the current advances on the topic. We begin by summarising the ways in which biologists measure the two components of tolerance, parasite load and fitness, as well as the ways in which the concept has been defined (i.e., point and range tolerance). It is common to test for variation in host tolerance according to intrinsic, innate factors, where variation exists among populations, genders or genotypes. Such variation in tolerance is pervasive across animal taxa, and we briefly review some of the mechanistic bases of variation that have recently begun to be explored. Three further novel advancements in the tolerance field are the appreciation of the role of extrinsic, environmental factors on tolerance, host tolerance in multi host-parasite systems and individual-based approaches to tolerance measures. We explore these topics using recent examples and suggest some future perspectives. It is becoming increasingly clear that an appreciation of tolerance as a defence strategy can provide significant insights into how hosts coexist with parasites. PMID- 27373337 TI - Structural Basis for Cooperative Function of Mettl3 and Mettl14 Methyltransferases. AB - N(6)-methyladenosine (m(6)A) is a prevalent, reversible chemical modification of functional RNAs and is important for central events in biology. The core m(6)A writers are Mettl3 and Mettl14, which both contain methyltransferase domains. How Mettl3 and Mettl14 cooperate to catalyze methylation of adenosines has remained elusive. We present crystal structures of the complex of Mettl3/Mettl14 methyltransferase domains in apo form as well as with bound S-adenosylmethionine (SAM) or S-adenosylhomocysteine (SAH) in the catalytic site. We determine that the heterodimeric complex of methyltransferase domains, combined with CCCH motifs, constitutes the minimally required regions for creating m(6)A modifications in vitro. We also show that Mettl3 is the catalytically active subunit, while Mettl14 plays a structural role critical for substrate recognition. Our model provides a molecular explanation for why certain mutations of Mettl3 and Mettl14 lead to impaired function of the methyltransferase complex. PMID- 27373339 TI - Biological invasions and host-parasite coevolution: different coevolutionary trajectories along separate parasite invasion fronts. AB - Host-parasite coevolution has rarely been observed in natural systems. Its study often relies on microparasitic infections introducing a potential bias in the estimation of the evolutionary change of host and parasite traits. Using biological invasions as a tool to study host-parasite coevolution in nature can overcome these biases. We demonstrate this with a cross-infection experiment in the invasive macroparasite Mytilicola intestinalis and its bivalve host, the blue mussel Mytilus edulis. The invasion history of the parasite is well known for the southeastern North Sea and is characterised by two separate invasion fronts that reached opposite ends of the Wadden Sea (i.e. Texel, The Netherlands and Sylt, Germany) in a similar time frame. The species' natural history thus makes this invasion an ideal natural experiment to study host-parasite coevolution in nature. We infected hosts from Texel, Sylt and Kiel (Baltic Sea, where the parasite is absent) with parasites from Texel and Sylt, to form sympatric, allopatric and naive infestation combinations, respectively. We measured infection rate, host condition and parasite growth to show that sympatric host parasite combinations diverged in terms of pre- and post-infection traits within <100 generations since their introduction. Texel parasites were more infective and more efficient at exploiting the host's resources. Hosts on Texel, on the other hand, evolved resistance to infection, whereas hosts on Sylt may have evolved tolerance. This illustrates that different coevolutionary trajectories can evolve along separate invasion fronts of the parasite, highlighting the use of biological invasions in studies of host-parasite coevolution in nature. PMID- 27373340 TI - Comparative transcriptomics of stickleback immune gene responses upon infection by two helminth parasites, Diplostomum pseudospathaceum and Schistocephalus solidus. AB - Immune systems of vertebrates are much more diverse than previously thought, in particular at the base of the vertebrate clade. RNA-seq was used to describe in detail the transcriptomic response of stickleback hosts to infection by two helminth parasites, the trematode Diplostomum pseudospathaceum (2 genotypes plus a genotype mix) and the cestode Schistocephalus solidus. Based on a global transcription profiling, we present immune genes that are active during chronic or multiple repeated infection. We found that the transcription profiles of D. pseudospathaceum genotypes were as divergent as those of the two parasite species. When comparing the host immune response, only 5 immune genes were consistently upregulated upon infection by both species. These genes indicated a role for enhanced toll like receptor (TLR) activity (CTSK, CYP27B1) and an associated positive regulation of macrophages (CYP27B1, THBS1) for general helminth defense. We interpret the largely differentiated gene expression response among parasite species as general redundancy of the vertebrate immune system, which was also visible in genotype-specific responses among the different D. pseudospathaceum infections. The present study provides the first evidence that IL4-mediated activation of T-helper lymphocyte cells is also important in anti-helminthic immune responses of teleost fish. PMID- 27373341 TI - Risk factors associated with recanalization of incompetent saphenous veins treated with radiofrequency ablation catheter. AB - PURPOSE: The purpose of this study was to determine the occlusion rate of incompetent great saphenous veins (GSVs) and small saphenous veins (SSVs) treated with radiofrequency ablation (RFA) and individualize variables associated with recanalization. MATERIALS AND METHODS: A retrospective review of 311 veins (256 GSVs and 55 SSVs) in 211 patients [177 women, 34 men; mean age, 45 years+/-12 (SD) (range: 18-75 years)] with incompetent GSVs and/or SSVs who were treated using new-generation RFA catheters was performed. The clinical results, occlusion rates, and variables associated with recanalization for the incompetent GSVs and SSVs were analyzed. RESULTS: No major complications were observed in the study population. Ten months after RFA, the occlusion rate was 89% (227/256) for GSVs and 91% (50/55) for SSVs. An increased pre-procedure diameter of the incompetent GSVs was associated with a higher rate of recanalization (OR: 0.825; 95% CI: 0.715-0.952) (P<0.05). No significant differences in age, gender, and side of treated veins were found between patients with recanalization of treated veins and those without recanalization. CONCLUSION: Our results show that pre-procedure diameter of the GSV is the single risk factor for recanalization after RFA. PMID- 27373342 TI - Testing Molecular Homogeneity at the Nanoscale with Massive Cluster Secondary Ion Mass Spectrometry. PMID- 27373343 TI - Ultradispersed Cobalt Ferrite Nanoparticles Assembled in Graphene Aerogel for Continuous Photo-Fenton Reaction and Enhanced Lithium Storage Performance. AB - The Photo-Fenton reaction is an advanced technology to eliminate organic pollutants in environmental chemistry. Moreover, the conversion rate of Fe(3+)/Fe(2+) and utilization rate of H2O2 are significant factors in Photo Fenton reaction. In this work, we reported three dimensional (3D) hierarchical cobalt ferrite/graphene aerogels (CoFe2O4/GAs) composites by the in situ growing CoFe2O4 crystal seeds on the graphene oxide (GO) followed by the hydrothermal process. The resulting CoFe2O4/GAs composites demonstrated 3D hierarchical pore structure with mesopores (14~18 nm), macropores (50~125 nm), and a remarkable surface area (177.8 m(2 )g(-1)). These properties endowed this hybrid with the high and recyclable Photo-Fenton activity for methyl orange pollutant degradation. More importantly, the CoFe2O4/GAs composites can keep high Photo Fenton activity in a wide pH. Besides, the CoFe2O4/GAs composites also exhibited excellent cyclic performance and good rate capability. The 3D framework can not only effectively prevent the volume expansion and aggregation of CoFe2O4 nanoparticles during the charge/discharge processes for Lithium-ion batteries (LIBs), but also shorten lithium ions and electron diffusion length in 3D pathways. These results indicated a broaden application prospect of 3D-graphene based hybrids in wastewater treatment and energy storage. PMID- 27373345 TI - Estrogen as an Environmental Pollutant. PMID- 27373344 TI - A novel role for pigment genes in the stress response in rainbow trout (Oncorhynchus mykiss). AB - In many vertebrate species visible melanin-based pigmentation patterns correlate with high stress- and disease-resistance, but proximate mechanisms for this trait association remain enigmatic. Here we show that a missense mutation in a classical pigmentation gene, melanocyte stimulating hormone receptor (MC1R), is strongly associated with distinct differences in steroidogenic melanocortin 2 receptor (MC2R) mRNA expression between high- (HR) and low-responsive (LR) rainbow trout (Oncorhynchus mykiss). We also show experimentally that cortisol implants increase the expression of agouti signaling protein (ASIP) mRNA in skin, likely explaining the association between HR-traits and reduced skin melanin patterning. Molecular dynamics simulations predict that melanocortin 2 receptor accessory protein (MRAP), needed for MC2R function, binds differently to the two MC1R variants. Considering that mRNA for MC2R and the MC1R variants are present in head kidney cells, we hypothesized that MC2R activity is modulated in part by different binding affinities of the MC1R variants for MRAP. Experiments in mammalian cells confirmed that trout MRAP interacts with the two trout MC1R variants and MC2R, but failed to detect regulation of MC2R signaling, possibly due to high constitutive MC1R activity. PMID- 27373346 TI - Comparison of mathematical methods for the evaluation of wastewater settleability by settling column tests. AB - Particulate matter (PM), which may serve as a vector of pollutants in both natural and human-impacted waters, is of primary interest in water quality studies, particularly for those conducted in urban areas. Separating solids from the liquid phase is one of the main goals of water treatment practices. Above all, the settling process is the most commonly used for this purpose. Generally, settling column tests are used in the laboratory to assess the total PM removal. Besides the traditional graphical method used for the interpretation of the laboratory results, other mathematical methods were developed - with the goal of simplifying the settling efficiency evaluation procedure and making it less subjective. To make a contribution in that direction, a study based on the comparison of four different mathematical methods for estimating PM removal efficiencies was conducted. The analysis was carried out on 15 samples of wastewater and showed that only two methods gave satisfactory results, and only one of them was physically based. Consequently, it is recommended to assess the overall PM removal, Etot, by a monoparametric exponential function, depending on the settling time (t) and on the first-order decay coefficient (k). PMID- 27373347 TI - Sentinel Lymph Node Frozen-Section Utilization Declines After Publication of American College of Surgeons Oncology Group Z0011 Trial Results With No Change in Subsequent Surgery for Axillary Lymph Node Dissection. AB - OBJECTIVES: To evaluate use of sentinel lymph node (SLN) frozen section (FS) before and after publication of the Z0011 trial. METHODS: We identified 116 pre Z0011 and 134 post-Z0011 patients from 18 months before and after Z0011-initiated changes. Clinicopathologic features were assessed by chart review. RESULTS: Post Z0011 SLN FS use markedly declined when performed with breast-conserving therapy (BCT) (P < .0001), with SLN FS in 53 (73.6%) of 72 and 19 (25.0%) of 76 in pre- and post-Z0011 groups, respectively. There was post-Z0011 decline in axillary lymph node dissection (ALND) (P = .014) but no difference in later procedures for ALND. SLN positivity was associated with larger (>=1.6 cm) tumor size (P = .002). Nodal upstage was more frequent with invasive lobular (3/32; 9.4%) vs other invasive (2/188; 1.1%) subtypes. CONCLUSIONS: Our findings support reduced need for SLN FS for BCT patients post-Z0011. However, those with specific clinicopathologic features may derive greater benefit from SLN FS. PMID- 27373348 TI - Toxicogenomic applications of Chinese rare minnow (Gobiocypris rarus) in aquatic toxicology. AB - Rare minnow (Gobiocypris rarus), a Chinese native species, are an excellent emerging model organism for aquatic toxicity testing and chemical safety assessment. "Big data" omics approaches (i.e., genomics, proteomics, and metabolomics) to inform mechanistic toxicology are now applied to studies in rare minnows to better understand toxicity and molecular pathways perturbed by chemicals. This review highlights recent applications of toxicogenomics to study changes in the gene and protein expression profiles in rare minnows in response to chemicals. Here we briefly describe studies that utilized cDNA microarrays in characterization of the cellular effects of rare minnows in single and mixed chemical exposures. Then we compare gel-based proteomics studies in liver of rare minnows following treatment with endocrine disrupting chemicals including 17beta estradiol, 17alpha-methyltestosterone, pentachlorophenol, and perfluorooctanoic acid. A total of 90 proteins identified in these studies were functionally annotated and categorized. These responsive proteins have roles in biological processes that include metabolism (37.8%), response to oxidation/chemicals (16.7%), signal transduction (11.1%), transport (10%), cytoskeleton (6.7%) and others (17.8%). In addition, recent investigations of endocrine disrupting effects and neurotoxicity of benzotriazole, an emerging contaminant, are summarized. The objective is to continue to enrich genome and protein databases for this species and to integrate molecular datasets to consider temporal effects and complex regulation at the level of the genome and proteome. PMID- 27373350 TI - Preventing the BDNF and NGF loss involved in the effects of cornel iridoid glycoside on attenuation of experimental autoimmune encephalomyelitis in mice. AB - The present study was designed to investigate the beneficial effects of cornel iridoid glycoside (CIG), a main component extract from Cornus officinalis, on neurotrophin expression in mouse experimental autoimmune encephalomyelitis (EAE), a classical model of multiple sclerosis (MS). After EAE initiation, CIG was intragastrically administered daily for 32 days and reduced disease severity. Histopathological staining and western blotting both showed that CIG could prevent brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) loss in the spinal cord of EAE mice. In conclusion, our findings indicated that CIG treatment suppressed disease severity of EAE partially through blocking downregulation of neurotrophic factor expression such as BDNF and NGF, suggesting that CIG may have beneficial effects for the treatment of demyelinating diseases such as MS. PMID- 27373349 TI - Local Patterns to Global Architectures: Influences of Network Topology on Human Learning. AB - A core question in cognitive science concerns how humans acquire and represent knowledge about their environments. To this end, quantitative theories of learning processes have been formalized in an attempt to explain and predict changes in brain and behavior. We connect here statistical learning approaches in cognitive science, which are rooted in the sensitivity of learners to local distributional regularities, and network science approaches to characterizing global patterns and their emergent properties. We focus on innovative work that describes how learning is influenced by the topological properties underlying sensory input. The confluence of these theoretical approaches and this recent empirical evidence motivate the importance of scaling-up quantitative approaches to learning at both the behavioral and neural levels. PMID- 27373351 TI - Digital monitoring and care: Virtual medicine. AB - Remote digital health monitoring technologies can be synergistically organized to create a virtual medical system providing more continuous care centered on the patient rather than the bricks and mortar medical complex. Utilization of the digitalized patient health monitoring can facilitate diagnosis, treatment plans, physician-patient interaction, and accelerate the progress of medical research, education, and training. The field of cardiac electrophysiology has been an early adopter of this shift in care and serves as a paradigm applicable to all areas of medicine. The overall impact of this remote virtual care model on the quality of medical care and patient experience requires greater study, as well as vigilance as to the differences between technology and care in order to preserve the intangible and immeasurable factors that bring humanity to the art and science of medicine. PMID- 27373352 TI - [The importance of"talk"between clinical laboratories and clinicians in precision medicine]. PMID- 27373353 TI - [The significance of clinical-examination communication in the total process of bone marrow cell morphology and bone marrow biopsy]. PMID- 27373354 TI - [The importance of communication between laboratory and clinic for hemostasis and thrombosis tests]. PMID- 27373355 TI - [The meaning and implement of clinical communication in accreditation of medical laboratory]. PMID- 27373357 TI - [Impact of extended-spectrum beta-lactamase on clinical outcome and medical cost in patients with bloodstream infection due to Klebsiella pneumoniae]. AB - OBJECTIVE: To evaluate the impact of extended-spectrum beta-lactamase (ESBL) on clinical outcome and medical cost in patients with bloodstream infection (BSI) due to Klebsiella pneumoniae. METHODS: A retrospective study was conducted in patients admitted into Changhai Hospital between January 2013 and December 2014, who suffered from BSI due to Klebsiella pneumoniae during hospitalization. Patients were divided into two groups according to whether Klebsiella pneumoniae produced ESBL (ESBL positive group and ESBL negative group). They were matched with propensity score matching method in a 1?1 ratio and then multiple regression model was used to analyze the impact of ESBL on clinical outcome and medical cost. Clinical outcome was evaluated by 30-day mortality post BSI; medical cost was evaluated by total length of stay (LOS), post-BSI LOS, total hospital cost and antimicrobial cost. RESULTS: Before matching, the two groups were significantly different in age, nosocomial infection rate, LOS before BSI and surgical rate during hospitalization (all P<0.05). The ESBL-positive group had higher 30-day mortality post BSI (21.3% vs 8.7%, P=0.054), and higher total LOS [25.0(12.0, 33.0) vs 16.0(10.0, 23.0) d, P=0.015], post-BSI LOS [16.0(9.0, 26.0) vs 10.0(5.0, 16.0) d, P=0.006], total hospital cost [69 409(40 605, 198 021) vs 45 683(28 448, 67 000) ?, P<0.001] and antimicrobial cost [10 279(4 815, 25 500) vs 3 783(1 596, 11 879) ?, P<0.001]. After matching, the two groups had no significant differences in clinical characteristics such as sex, age, nosocomial infection rate, LOS before BSI, APACHEII score, Charlson Comorbidity Index, underlying diseases and surgical rate during hospitalization (all P>0.05). Multiple regression analysis indicated that ESBL could significantly increase the total LOS, post-BSI LOS, total hospital cost and antimicrobial cost (all P<0.001), but did not increase the 30-day mortality post BSI (P=0.910). CONCLUSIONS: ESBL can significantly increase the medical cost in patients with BSI due to Klebsiella pneumoniae but does not increase the 30-day mortality post BSI. PMID- 27373356 TI - [Clinical features of irritable bowel syndrome with small intestinal bacterial overgrowth and a preliminary study of effectiveness of Rifaximin]. AB - OBJECTIVE: To investigate the prevalence and clinical features of small intestinal bacterial overgrowth (SIBO) in diarrhea-predominant irritable bowel syndrome (IBS-D) patients detected by hydrogen and methane in lactulose breath test (LBT), and to study the effects of rifaximin in IBS-D patients. METHODS: Consecutive patients with IBS-D who met Rome III criteria, and gender- and age matched healthy volunteers were enrolled from March 2015 to January 2016 in Peking University Third Hospital. All the ISB-D patients underwent LBT to detect the prevalence of SIBO. The clinical and LBT features of IBS with SIBO (IBS-P group) and without SIBO (IBS-N group) were analyzed. The effects of rifaximin therapy (0.4 g, twice per day for 4 weeks) in IBS-D patients were evaluated by comparing changes in clinical features and LBT results after treatment. RESULTS: (1) Eighty-four IBS-D patients and 22 healthy controls were enrolled. The prevalence of SIBO in IBS-D patients was 41.67% (35/84), with 27 (77.14%) only hydrogen-positive, 5 (14.29%) methane-positive, and 3 (8.57%) both methane- and hydrogen-positive. (2) The body mass index (BMI) in the IBS-P group was lower than in the IBS-N group [(21.61+/-0.57) vs (23.44+/-0.54) kg/m(2,) P<0.05], the maximum stool frequency was also less than in the IBS-N group [(3.85+/-0.23) vs (4.88+/-0.35) times/day, P<0.05]. (3) No significant difference was found in oro cecal transit time (OCTT) among IBS-P, IBS-N and healthy controls. The hydrogen concentration in small intestinal and colonic sections in breath of the IBS-P group was higher than that of both healthy controls and the IBS-N group, while methane concentration in small intestinal and colonic sections (160 min) was higher than that of the IBS-N group (all P<0.05). (4) There was no linear relationship between mean hydrogen and methane concentrations in LBT among the IBS-P, the IBS-N and healthy control groups (all r<0.35, P>0.05). (5) Totally 13 IBS-P patients received rifaximin therapy, in whom the symptoms of abdomen pain, bloating, fecal consistency, stool frequency, and stool satisfactory were significantly improved after treatment (all P<0.05); 8 IBS-N patients received rifaximin therapy, in whom fecal consistency, stool frequency, and satisfactory were significantly improved (all P<0.05). (6) And 5/13 of the IBS-P patients receiving rifaximin presented negative LBT results after rifaximin therapy, with lower hydrogen concentration at all the time points, especially in colonic section (120 min) [(34.54+/-7.32) *10(-6) vs (52.23+/-9.40) *10(-6,) P<0.05] and lower methane concentration especially in small intestinal section (80 min) [(8.54+/-0.95) *10(-6) vs (11.31+/-0.94) *10(-6,) P<0.05]. CONCLUSIONS: About 41.67% of the IBS-D patients meeting Rome III criteria have SIBO, which can be better screened by combining hydrogen and methane in LBT compared with only hydrogen in LBT. SIBO can affect nutritional status in IBS-D patients. Rifaximin can improve the systematic symptoms of IBS-D patients with SIBO, also reduce hydrogen and methane concentration in breath, while only improving diarrhea in IBS-D patients without SIBO. Some differences in gut microbiota may exist between IBS-D with and without SIBO. PMID- 27373358 TI - [Effects of intranasal midazolam premedication on inhaled induction of anesthesia with sevoflurane of pediatric patients]. AB - OBJECTIVE: To evaluate the effects of intranasal midazolam premedication on children who undergoing inhaled induction of anesthesia with sevoflurane. METHODS: One hundred American Society of Anesthesiologists(ASA)I-II children undergoing elective operations in Tianjin Medical University Cancer Institute and Hospital from June 2014 to June 2015 were randomly assigned into 2 groups, and 50 cases in each group. Patients received different intranasal premedication giving 30 min before anesthesia: midazolam 0.3 mg/kg (control group) and normal saline (placebo group) 2 ml. The following data were observed: the anxiety scores of the children in the preoperative interview (T1), before intranasal premedication (T2), during the induction room play (T3) and in the beginning of sevoflurane inhaled induction (T4) using Modified Yale Preoperative Anxiety Scale (m-YPAS); the satisfaction scores of parents when children entering the operating room using Visual Analogue Scale (VAS); and the cooperation scores of the children receiving the sevoflurane-inhaled induction using Induction Compliance Checklist (ICC). The process of induction, the induction of sevoflurane and adverse incident were recorded. RESULTS: The scores of m-YPAS of the induction room play (T3) and in the beginning of sevoflurane-inhaled induction (T4) of the control group were (26.48+/-9.04) and (40.88+/-17.31)scores, while those of the placebo group were (32.38+/-10.67) and (56.50+/-20.02) scores. The m-YPAS scores of the control group were significantly lower than those of the placebo group (t=2.983, 4.173, all P<0.05). The VAS of the control group and placebo group were (6.55+/ 1.55) and (8.18+/-1.46) scores, the VAS of the control group was significantly lower than that of the placebo group (t=5.504, P<0.05). The total time of induction of the control group was (84.35+/-22.47)s, which was significantly shorter than that of the placebo group((104.21+/-31.05)s, t=3.664, P<0.05). The scores of m-YPAS in the preoperative interview (T1), before intranasal premedication (T2), the scores of ICC, the time of closing eyes and excitement phase of 2 groups had no significant difference (all P>0.05). There was no adverse incident happened in both groups. CONCLUSIONS: Intranasal midazolam provided as premedication can reduce the anxiety for children undergoing inhaled induction of anesthesia with sevoflurane, and shorten the time of induction. It's a safe and effective method for premedication of pediatric anesthesia. PMID- 27373359 TI - [Analysis of disease spectrum of biliary surgery among 30 years in a single center]. AB - OBJECTIVE: To explore the changing trend and clinical significance of disease spectrum of biliary surgery among 30 years in PLA General Hospital. METHODS: We retrospectively analyzed the clinical data of 21 189 consecutive patients with biliary diseases in PLA General Hospital between January 1985 and December 2014 according to the inclusion criteria. Taking 5 years as a research group, all patients were divided into 6 groups, and then the 30 years of the disease spectrum of biliary surgery was described. RESULTS: (1) From January 1985 to December 2014, the PLA General Hospital performed 21 189 cases of patients with biliary surgery diseases, including 9 460 cases of male, 11 729 cases of female (female?male=1.24?1). The average age was 52.1+/-13.5 years old (6-98 years). (2) Of the all cases, the most patients was cholelithiasis, accounting for 65.26%, and gallbladder stones accounting for 53.61%. The following disease was cholangiocarcinoma, accounting for 12.79%, and hilar cholangiocarcinoma accounting for 5.95%. (3) From the perspective of disease spectrum changing trend, the proportion of patients with cholelithiasis were decreased gradually, from 74.9% to 65.2%, while the proportion of patients with cholangiocarcinoma showed a gradual upward trend, rising from 6% to 14% (P<0.05); and the proportion of bile duct cystic dilatation and gallbladder carcinoma shared a gradual increase(P<0.05), however, the variation of proportion of gallbladder polyps and biliary stricture were not statistically significant (P>0.05). (4) In patients with cholelithiasis, the proportion of patients with gallbladder stones increased gradually from 71.9% to 82%, while the proportion of patients with bile duct stones decreased gradually from 28.1% to 18%. There was no statistical significance in the proportion of different types of cholangiocarcinoma patients (P>0.05) (40% of the patients with hilar cholangiocarcinoma, 25% of the intrahepatic cholangiocarcinoma, and 35% of the extrahepatic cholangiocarcinoma). CONCLUSION: With the time changing, the disease spectrum of biliary surgery has also changed. The proportion of patients with cholelithiasis, especially the patients with bile duct stones, was declining gradually, and the proportion of patients with cholangiocarcinoma was increasing gradually. PMID- 27373360 TI - [Clinical possibility of low ligation of inferior mesenteric artery and lymph nodes dissection in laparoscopic low anterior resection]. AB - OBJECTIVE: To investigate the clinical possibility of low ligation of inferior mesenteric artery (IMA) and lymph nodes dissection in laparoscopic low anterior resection. METHODS: Data was collected retrospectively from 216 patients who underwent laparoscopic low anterior resection in our hospital from June 2011 to January 2015.Patients were divided into control group (132 cases) and observation group (84 cases). The observation group was treated with low ligation of IMA and lymph nodes dissection, and the control group was cured by high ligation of IMA and lymph nodes dissection. We analyzed the operation time, the number of lymph nodes dissection, the number of lymph nodes removed around the root of IMA, the rate of lymph node metastasis around the root of IMA, the incidence of anastomotic leakage and the ventilation time after the operation. RESULTS: There was no significant difference between the two group in the pre-operative data, operation time, the number of lymph nodes dissection the number of lymph nodes removed around the root of IMA, the rate of lymph node metastasis around the root of IMA and the incidence of anastomotic leakage (P>0.05). The observation group were significantly better than the control group the in the ventilation time after the operation (P<0.05). The follow up time was 12 to 67 months. The median follow up time was 37 months. One patient in observation group died of cardiovascular disease. One patient in control group died of metastatic carcinoma. CONCLUSION: Detection of low ligation of inferior mesenteric artery and lymph nodes dissection in laparoscopic low anterior resection is safe and practicable, which should be widely applied. PMID- 27373361 TI - [Prenatal diagnosis of Thailand deletion of alpha-thalassemia 1 families]. AB - OBJECTIVE: To conduct analysis and prenatal diagnosis on 11 couples carrying Thailand deletion (--(THAlphaI)) alpha-thalassemia 1, so as to provide information for clinical genetic counseling on alpha-thalassemia 1. METHODS: Altogether 11 Thailand deletion (--(THAlphaI)) alpha-thalassemia 1 families were collected from Fujian Maternal and Children Health Hospital from May 2009 to September 2015. Gap-polymerase chain reaction (gap-PCR) and reverse dot blot (RDB) technology were used to detect the thalassemia mutations in the couples and fetuses. RESULTS: In one family, Thailand deletion alpha-thalassemia 1 was detected in both the pregnant woman and her husband. In 10 families, Thailand deletion alpha-thalassemia 1 was detected in either the pregnant women or the husband, while the spouses had alpha-thalassemia heterozygote (1 combined with beta thalassemia heterozygote). Thailand deletion alpha-thalassemia 1 family members all had lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). In prenatal diagnosis of the 12 fetuses, 4 fetuses were found with hemoglobin(Hb) Bart's hydrops fetalis syndrome, 5 were with alpha thalassemia heterozygote, and 3 were normal. CONCLUSIONS: For couples with positive hematological phenotype but normal results in routine genetic examination of alpha-thalassemia, attention should be paid especially for with a history of having babies of hydrops fetalis syndrome or hemoglobin H disease. It is necessary to consider the possibility of the rare Thailand deletion (- (THAlphaI)) alpha-thalassemia 1. Prenatal diagnosis for high-risk families plays an important role. PMID- 27373362 TI - [Analysis of treatment and prognosis in post-operative patients with urachal carcinoma]. AB - OBJECTIVE: Urachal carcinoma is a kind of urogenital tract malignancy with a very low incidence. The objective of this study was to observe the clinical presentation, pathological condition, treatment method and outcome of patients with urachal carcinoma. METHODS: A retrospective analysis of thirty-six cases of urachal carcinoma diagnosed over a period of 10 years from 2003 to 2013 was carried out. All pathologic specimens were reviewed by two separate pathologists. Clinical and histological features, treatment condition, patient follow-up and survival outcome was reviewed and calculated. RESULTS: The mean age at diagnosis was 53 years. Of the thirty-six patients, twenty-five were male. All patients underwent partial cystectomy with bilateral pelvic lymph node dissection. All cases were adenocarcinoma, including 20 mucinous adenocarcinoma, 7 moderately differentiated adenocarcinoma, 5 poorly differentiated adenocarcinoma, 1 signet ring cell carcinoma, 3 hybrid adenocarcinoma. The Sheldon pathologic stage was stage II in 11, III in 16 and IVa in 9 cases. All patients received medical oncological therapy. The median follow-up period was 27 months. The median overall survival was 36 months. One-year survival rate was 70% and five-year survival rate was 28%. CONCLUSIONS: Urachal carcinomas are rare and usually at locally advanced stage at diagnosis with a high tendency of metastases. Surgery is a key method of primary treatment and medical oncological therapy may play a role in decreasing the chances of recurrence which still needs to be explained by prospective clinical trials. PMID- 27373363 TI - [The application and mechanism analysis of postoperative intracranial pressure monitoring in giant meningioma(clinical analysis of 7 cases)]. AB - OBJECTIVE: To investigate varying patterns of intracranial pressure(ICP)after giant meningioma resection and analyze the causes of the variation of ICP in different postoperative phases. METHODS: Clinical data, surgical approachs and the ICP monitoring data of 7 patients with giant meningioma in different positions who were admitted to the First Affiliated Hospital of Soochow University from October 2013 to July 2014 and received microsurgical resection via different approachs were analysed retrospectively. The tumour locations were in convexity(n=1), olfactory groove(n=1), sphenoidal ridge(n=2), parasagittal(n=1), falx(n=1), petroclival(n=1) and resected via longitudinal fissure approach, subfrontal approach, extensive pterional approach, subtemporal approach. ICP monitoring probe was placed subdurally and average monitoring time was 9 days. Dehydrating agent was administered in all cases postoperatively. RESULTS: Tumors were totally resected (Simpson Grade I or II ) in all patients. The increase of ICP was observed on the 3(rd) day, peaked on the 4(th) day and reduced to normal on the 5(th)-7(th) day. Decompressive craniectomy and tracheotomy were performed in one case due to consciousness deterioration, severe brain edema and continuous ICP augment on the third day after operation. All the patients recovered well except for the cerebrospinal fluid rhinorrhea occurring in one case postoperatively, whose symptom ameliorated significantly after conservative treatment. CONCLUSION: ICP monitoring exerts an important role on the postoperative management of giant meningioma. Simultaneously, The summary of vast ICP monitoring data concerning to giant meningioma provides the evidence and experience for protecting neurological function via abundant preoperative preparations, reasonable operative approach, careful postoperative management. PMID- 27373364 TI - [Regulation effect of beta-catenin pathway on TGF-beta1 induced pulmonary pro fibrosis]. AB - OBJECTIVE: To investigate the regulation effect of beta-catenin pathway on transforming growth factor beta1 (TGF-beta1) induced pulmonary pro-fibrosis. METHODS: The rat alveolar typeII cells (RLE-6TN) were divided into four groups: A1.control group; B1.TGF-beta1 group was treated with 5 MUg/L TGF-beta1; C1.pcDNA+ TGF-beta1 group was transiently transfected with eukaryotic expression vector pcDNA3.0 (pcDNA) and followed by TGF-beta1 treatment (5 MUg/L); D1.F-(beta TrCP)-Ecad+ TGF-beta1 group was transiently transfected with beta-catenin protein knockout vector [F-(beta-TrCP)-Ecad] and followed by TGF-beta1 treatment (5 MUg/L). After 24 hours, cells were observed under the inverted phase contrast microscope, then the expressions of E-cadherin, alpha-smooth muscle actin (alpha SMA) and fibronectin (Fn) in each group were measured by Western blot and the mRNA levels of Snail which was the downstream profibrotic transcription production in cell culture supernatants of each group were detected by real-time fluorescence quantification-polymerase chain reaction (RT-PCR) .The rat alveolar macrophages (CRL-2192) were divided into five groups: A2.control group; B2.Interferon gamma (IFN-gamma) group was treated by 20 MUg/L IFN-gamma; C2.TGF beta1+ IFN-gamma group was treated by 20 MUg/L IFN-gamma with 10 MUg/L TGF-beta1; D2.F-(beta-TrCP)-Ecad+ TGF-beta1+ IFN-gamma group was transfected with F-(beta TrCP)-Ecad and other dispose was the same as group C2; E2.WTbeta-catenin+ TGF beta1+ IFN-gamma group was transfected with WTbeta-catenin and other dispose was the same as group C2.After 24 hours, protein levels of beta-catenin in group A2, B2, C2 were determined by Western blot.Inducible nitric oxide synthase (iNOS) mRNA levels of each group were detected by RT-PCR. RESULTS: The RLE-6TN cells of group B1, C1 showed a change in morphology to spindle-shaped cells, the cells of group D1 maintained a cobblestone morphology. Protein expressions of the fibroblast markers alpha-SMA and Fn, and mRNA expressions of the downstream profibrotic transcription production Snail of group B1, C1 were significantly higher than group A1, while protein expressions of the epithelial marker E cadherin were significantly lower.The protein expressions of alpha-SMA, Fn and mRNA expressions Snail of group D1 were significantly lower than group C1 (0.352+/-0.076 vs 0.937+/-0.303, 0.319+/-0.072 vs 0.903+/-0.211, 3.675+/-0.642 vs 9.708+/-2.031), while the protein expressions of E-cadherin were significantly higher (1.482+/-0.227 vs 0.604+/-0.121) (all P<0.05). The steady state protein levels of beta-catenin in CRL-2192 cells was low and beta-catenin protein expressions of CRL-2192 cells in group A2, B2 and C2 had no significantly statistical differences.The mRNA expressions of iNOS of group B2 cells were significantly higher than group A2, C2, D2, E2 (64.95+/-4.47 vs 9.87+/-0.73, 21.32+/-2.41, 18.35+/-3.61, 22.87+/-3.14) (all P<0.01), the expressions of iNOS of group C2, D2, E2 were all higher than group A2 (all P<0.05), but there were no significant differences among group C2, D2 and E2. CONCLUSIONS: Inhibition of beta-catenin pathway inhibits TGF-beta1-induced epithelial-mesenchymal transition (EMT) and has no effect on its anti-inflammation effect.Therefore, beta-catenin pathway regulates the pulmonary pro-fibrosis effect of TGF-beta1. PMID- 27373365 TI - [The influence of lumbar sympathetic ganglion radiofrequency thermocoagulation on the activation of microglia in rats with diabetic neuropathic pain]. AB - OBJECTIVE: To observe the influence of lumbar sympathetic ganglion radiofrequency thermocoagulation on the activation of spinal microglia in rats with diabetic neuropathic pain (DNP). METHODS: Thirty-six painful diabetic Sprague-Dawley rats induced by 60 mg/kg streptozotocin (STZ) intraperitoneal injection were randomly divided into diabetic neuropathic pain group (group DNP, n=12), Sham operation group (group Sham, n=12) and radiofrequency thermocoagulation group (group R, n=12). Meanwhile another 12 age-matched rats were allocated as normal control group (group N), rats in group N received intraperitoneal injection of equal volume of normal saline. Twenty-eight days after STZ injection, rats in group R received L3 lumbar sympathetic ganglia radiofrequency thermocoagulation on the left side under X-ray guideline after anesthesia with damage time 60 s and damage temperature 60 C. Rats in group Sham received puncture positioning, but not thermocoagulation therapy. The mechanical paw withdrawal threshold (PWT) were performed before STZ injection, 7, 14, 21, 28 days after STZ injection and 1, 3, 5, 7, 14 days after radiofrequency thermocoagulation, respectively. Blood glucose were performed before STZ injection, 3, 28 days after STZ injection and 1, 14days after radiofrequency thermocoagulation. After the final behavioral testing, L3-L5 spinal cord tissues were removed to exam the expression of microglia marker OX42 by Western blotting and immunofluorescence technique, and the changes in the expression of inflammation factor IL-1beta, IL-6, TNF-alpha were detected by ELISA technique. RESULTS: Compared with group N, after 14, 21, 28 days of STZ injection and 1, 3, 5, 7, 14 days of radiofrequency thermocoagulation, the PWT of group DNP and group Sham decreased significantly (P<0.05); Before radiofrequency thermocoagulation, the PWT of rats in group DNP was (3.84+/-0.83) g, the PWT of rats in group R was (4.45+/-0.88) g, there was no statistically significant difference between group DNP and group R (t=1.514, P>0.05), but after radiofrequency thermocoagulation, compared with DNP group, the PWT of rats in group R increased significantly (P<0.05), and lasted to 14 d after radiofrequency thermocoagulation. The ratio of spinal microglia marker OX42 and GAPDH, the expression of inflammation factor IL-1beta, IL-6, and TNF-alpha in group N were 0.074+/-0.023, (35.93+/-6.16) pg/ml, (92.11+/-13.23) pg/ml, and (169.50+/-22.64) pg/ml, respectively. The ratio of spinal microglia marker OX42 and GAPDH, the expression of inflammation factor IL-1beta, IL-6, and TNF-alpha in group DNP were 1.023+/-0.185, (73.82+/-9.25) pg/ml, (155.33+/-21.82) pg/ml, and (298.30+/-33.21) pg/ml, respectively. The ratio of spinal microglia marker OX42 and GAPDH, the expression of inflammation factor IL-1beta, IL-6, and TNF-alpha in group Sham were 0.951+/-0.103, (73.00+/-7.54) pg/ml, (151.02+/-24.26) pg/ml, and (294.01+/ 36.37) pg/ml, respectively. The ratio of spinal microglia marker OX42 and GAPDH, the expression of inflammation factor IL-1beta, IL-6, and TNF-alpha in group R were 0.563+/-0.019, (51.81+/-7.36) pg/ml, (123.24+/-16.13) pg/ml, and (229.23+/ 29.16) pg/ml, respectively. Compared with group N, the expression of spinal microglia marker OX42 and inflammation factor IL-1beta, IL-6, and TNF-alpha in group DNP, group Sham and group R increased significantly (F=7.501, 348.698, 568.021, 145.110, all P<0.05). Compared with DNP group, the expression of spinal microglia marker OX42 and inflammation factor IL-1beta, IL-6, and TNF-alpha of group R reduced significantly (all P<0.05). CONCLUSION: The lumbar sympathetic ganglion radiofrequency thermocoagulation can alleviate diabetic neuropathic pain. The mechanism may relate with the inhibition of spinal microglia activation and the lower expression of inflammation factor. PMID- 27373366 TI - Influence of Environmental Factors on the Active Substance Production and Antioxidant Activity in Potentilla fruticosa L. and Its Quality Assessment. AB - Environmental factors may influence types and contents of active substances. This study investigated the influence of environmental factors on the active substance contents and antioxidant activity of Potentilla fruticosa L. from different regions of China. Also, HPLC fingerprint similarity analysis (SA) coupled with hierarchical cluster analysis (HCA) and discriminant analysis (DA) were further introduced for the accurate classification and quality assessment of P. fruticosa. The results showed that altitude was significantly and negatively correlated to the content of tannin (P < 0.05). Annual sunshine duration and altitude were significantly and positively correlated to the flavonoids content, rutin content and antioxidant activity (P < 0.05). Annual mean temperature was significantly and negatively correlated to the content of total phenolics, while altitude was significantly and positively correlated to the content of total phenolics (P < 0.05). Eight samples were unambiguously separated into three groups. Two types of discriminant functions with a 100% discrimination ratio were constructed. All data consistently supported the conclusion that P. fruticosa produced from Kangding, Sichuan Province had high quality among all samples, therefore, Kangding in Sichuan Province with favorable environmental conditions is recommended as a preferable production location. PMID- 27373367 TI - 2-Aminoethoxydiphenyl Borate Potentiates CRAC Current by Directly Dilating the Pore of Open Orai1. AB - 2-Aminoethoxydiphenyl borate (2-APB) elicits potentiation current (Ip) on Ca(2+) release-activated Ca(2+) (CRAC) channels. An accurate investigation into this modulation mechanism would reveal how STIM1-dependent channel gating is enhanced, and benefit the future immune enhancer development. Here, we directly probed the pore diameter of CRAC channels and found that 2-APB enlarged the pore size of STIM1-activated Orai1 from 3.8 to 4.6 A. We demonstrated that ions with small sizes, i.e., Ca(2+) and Na(+), mediated prominent 2-APB-induced Ip on the wildtype (WT) Orai1 channels of narrow pore sizes, while conducted decreased or no Ip on Orai1-V102C/A/G mutant channels with enlarged pore diameters. On the contrary, large Cs(+) ions blocked the WT channels, while displayed large 2-APB induced Ip on pore-enlarged Orai1-V102C/A/G mutant channels, and the potentiation ratio was highest on Orai1-V102C with an intermediate pore size. Furthermore, we showed that 2-APB potentiated Cs(+) current on constitutively active Orai1 V102C/A/G mutants independent of STIM1. Our data suggest that 2-APB directly dilates the pore of open Orai1 channels, both ion size and pore diameter jointly determine the amplitude of Ip on CRAC channels, and the generation of Ip requires the open state of Orai1, not STIM1 itself. PMID- 27373368 TI - Continued Role of Splenectomy in the Management of Patients With Myelofibrosis. PMID- 27373370 TI - Neuroimaging supports behavioral personality assessment: Overlapping activations during reflective and impulsive risk taking. AB - Personality assessment has been challenged by the fact that different assessment methods (implicit measures, behavioral measures and explicit rating scales) show little or no convergence in behavioral studies. In this neuroimaging study we address for the first time, whether different assessment methods rely on separate or overlapping neuronal systems. Fifty nine healthy adult participants completed two objective personality tests of risk propensity: the more implicit Balloon Analogue Risk Task (BART) and the more explicit Game of Dice Task (GDT). Significant differences in activation, as well as connectivity patterns between both tasks were observed. In both tasks, risky decisions yielded significantly stronger activations than safe decisions in the bilateral caudate, as well as the bilateral Insula. The finding of overlapping brain areas validates different assessment methods, despite their behavioral non-convergence. This suggests that neuroimaging can be an important tool of validation in the field of personality assessment. PMID- 27373369 TI - The neuritic plaque facilitates pathological conversion of tau in an Alzheimer's disease mouse model. AB - A central question in Alzheimer's Disease (AD) is whether the neuritic plaque is necessary and sufficient for the development of tau pathology. Hyperphosphorylation of tau is found within dystrophic neurites surrounding beta amyloid deposits in AD mouse models but the pathological conversion of tau is absent. Likewise, expression of a human tau repeat domain in mice is insufficient to drive the pathological conversion of tau. Here we developed an Abeta amyloidosis mouse model that expresses the human tau repeat domain and show that in these mice, the neuritic plaque facilitates the pathological conversion of wild-type tau. We show that this tau fragment seeds the neuritic plaque-dependent pathological conversion of wild-type tau that spreads from the cortex and hippocampus to the brain stem. These results establish that in addition to the neuritic plaque, a second determinant is required to drive the conversion of wild type tau. PMID- 27373371 TI - Theta phase coherence in affective picture processing reveals dysfunctional sensory integration in psychopathic offenders. AB - Psychopathic offenders are described as emotionally cold, displaying deficits in affective responding. However, research demonstrates that many of the psychopathy related deficits are moderated by attention, such that under conditions of high attentional and perceptual load psychopathic offenders display deficits in affective responses, but do not in conditions of low load. To date, most studies use measures of defensive reflex (i.e., startle) and conditioning manipulations to examine the impact of load on psychopathy-related processing, but have not examined more direct measures of attention processing. In a sample of adult male offenders, the present study examined time-frequency EEG phase coherence in response to a picture-viewing paradigm that manipulated picture familiarity to assess neural changes in processing based on perceptual demands. Results indicated psychopathy-related differences in the theta response, an index of readiness to perceive and integrate sensory information. These data provide further evidence that psychopathic offenders have disrupted integration of sensory information. PMID- 27373372 TI - Identification of Novel FAM134B (JK1) Mutations in Oesophageal Squamous Cell Carcinoma. AB - Mutation of FAM134B (Family with Sequence Similarity 134, Member B) leading to loss of function of its encoded Golgi protein and has been reported induce apoptosis in neurological disorders. FAM134B mutation is still unexplored in cancer. Herein, we studied the DNA copy number variation and novel mutation sites of FAM134B in a large cohort of freshly collected oesophageal squamous cell carcinoma (ESCC) tissue samples. In ESCC tissues, 37% (38/102) showed increased FAM134B DNA copies whereas 35% (36/102) showed loss of FAM134B copies relative to matched non-cancer tissues. Novel mutations were detected in exons 4, 5, 7, 9 as well as introns 2, 4-8 of FAM134B via HRM (High-Resolution Melt) and Sanger sequencing analysis. Overall, thirty-seven FAM134B mutations were noted in which most (31/37) mutations were homozygous. FAM134B mutations were detected in all the cases with metastatic ESCC in the lymph node tested and in 14% (8/57) of the primary ESCC. Genetic alteration of FAM134B is a frequent event in the progression of ESCCs. These findings imply that mutation might be the major driving source of FAM134B genetic modulation in ESCCs. PMID- 27373373 TI - Zeolite/iron oxide composite as sorbent for magnetic solid-phase extraction of benzene, toluene, ethylbenzene and xylenes from water samples prior to gas chromatography?mass spectrometry. AB - This study reports a new composite based on ZSM-5 zeolite decorated with iron oxide magnetic nanoparticles as a valuable sorbent for magnetic solid-phase extraction (MSPE). A proposal is made to determine benzene, toluene, ethylbenzene and xylenes (BTEX) as model analytes in water samples using gas chromatography mass spectrometry. A two-step multivariate optimization strategy, using Plackett?Burman and circumscribed central composite designs, was employed to optimize experimental parameters affecting MSPE. The method was evaluated under optimized extraction conditions (i.e., amount of sorbent, 138mg; extraction time, 11min; sample pH, pH of water (i.e., 5.5?6.5); eluent solvent volume, 0.5mL; and elution time, 5min), obtaining a linear response from 1 to 100MUgL(?1) for benzene; from 10 to 100MUgL(?1) for toluene, ethylbenzene and o-xylene; and from 10 to 75MUgL(?1) for m,p-xylene. The repeatability of the proposed method was evaluated at a 40MUgL(?1) spiking level and coefficients of variation ranged between 8 and 11% (n=5). Limits of detection were found to be 0.3MUgL(?1) for benzene and 3MUgL(?1) for the other analytes. These values satisfy the current normative of the Environmental Protection Agency and European Union for BTEX content in waters for human consumption. Finally, drinking water, wastewater and river water were selected as real water samples to assess the applicability of the method. Relative recoveries varied between 85% and 114% showing negligible matrix effects. PMID- 27373374 TI - Purification of organic acids by chromatography with strong anionic resins: Investigation of uptake mechanisms. AB - Bio-based organic acids are promising renewable carbon sources for the chemical industry. However energy-consuming purification processes are used, like distillation or crystallization, to reach high purities required in some applications. That is why preparative chromatography was studied as an alternative separation technique. In a previous work dealing with the purification of lactic, succinic and citric acids, the Langmuir model was insufficient to explain the elution profiles obtained with a strong anionic resin. Consequently the Langmuir model was coupled with a usual ion-exchange model to take into account the retention of their conjugate bases (<2%), which are commonly neglected at low pH (<1.5). Elution simulations with both uptake mechanisms fitted very well with experimental pulse tests. Only two parameters were optimized (equilibrium constant of acid uptake and ion-exchange selectivity coefficient of conjugate base) and their value were coherent with experimental and resin suppliers' data. These results confirmed that the singular tailing and apparent delay observed with succinic and citric acids can be explained by the high affinity of succinate and citrate for resin cationic sites. The model was implemented in a preparative chromatography simulation program in order to optimize operating parameters of our pilot-scale ISMB unit (Improved Simulated Moving Bed). The comparison with experimental ISMB profiles was conclusive. PMID- 27373375 TI - Determination of 15 N-nitrosodimethylamine precursors in different water matrices by automated on-line solid-phase extraction ultra-high-performance-liquid chromatography tandem mass spectrometry. AB - A new methodology based on on-line solid-phase extraction (SPE) ultra-high performance-liquid chromatography coupled to a triple quadrupole mass spectrometer (UHPLC-MS-MS) for the determination of 15 individual anthropogenic N nitrosodimethylamine (NDMA) precursors was developed. On-line SPE was performed by passing 2mL of the water sample through a Hypersil GOLD aQ column and chromatographic separation was done using a Kinetex Biphenyl column using methanol and 0.1% formic acid aqueous solution as a mobile phase. For unequivocal identification and confirmation, two selected reaction monitoring (SRM) transitions were monitored per compound. Quantification was performed by internal standard approach and matrix match calibration. The main advantages of the developed method are high sensitivity (limits of detection in the sub ng/L range), selectivity due to the use of tandem mass spectrometry, precision and minimum sample manipulation as well as fast analytical response. Process efficiency and recovery were also evaluated for all the target compounds. As part of the validation procedure, the method was applied in a sampling campaign for the analysis of influent and secondary effluent of a wastewater treatment plant (WWTP) in Girona, Spain. Additionally, the effluent from a nanofiltration (NF) membrane system used for water recycling was monitored. The percentage of NDMA formation explained by the measured precursors was also quantified. PMID- 27373376 TI - Micro-solid phase extraction followed by thermal extraction coupled with gas chromatography-mass selective detector for the determination of polybrominated diphenyl ethers in water. AB - A method of analyzing environmental contaminants in water based on micro-solid phase extraction (MU-SPE) followed by thermal extraction (TE) and a cold-trapping step, coupled with gas chromatography-mass selective detection (GC-MSD) was developed and validated. MU-SPE-TE- GC-MSD was employed in the determination of five polybrominated diphenyl ethers. The MU-SPE sorbent was chitosan-graphene oxide (CS-GO) composite, which was prepared by mixing CS and GO by means of ultrasonication. The CS in the composite was cross-linked with glutaraldehyde. After MU-SPE, the analytes in the extract were extracted thermally in a thermal desorption unit tube combined with a cooled injection system, coupled to GC-MSD. The extraction conditions were optimized for the detection of the target compounds in water. This method provided linearity ranges of between 0.1 and 20MUgL(-1) (depending on the analytes), with coefficients of determination, r(2), >=0.9982. The calculated relative recoveries were between 71.52 and 96.15% whereas precision (based on % relative standard deviations) was between 3.54 and 11.36%. The method showed limit of detection and limit of quantification ranges of between 0.007 and 0.016MUgL(-1), and between 0.023 and 0.054MUgL(-1), for the two groups of analytes, respectively. The method was applied to the determination of the target analytes in water. PMID- 27373377 TI - Response to Letter to the Editor by T. Matys Grygar, 2015 Assessment of the contamination of riparian soil and vegetation by trace metals - A Danube River case study. PMID- 27373378 TI - Land use and soil contamination with Toxoplasma gondii oocysts in urban areas. AB - Because soil contaminated with Toxoplasma gondii oocysts is increasingly recognized as a major source of infection for humans, in this study, we investigated the spatial pattern of soil contamination with T. gondii oocysts in urban area of northeastern Mainland China. From April 2014 to May 2015, more than 9000 soil samples were collected. Detection of T. gondii oocysts was performed applying real-time quantitative PCR. Sensitivity was improved by analyzing four replicates for each sampling point. T. gondii was detected in 30.3% of all samples. Subsequently, a maximum entropy model was used to evaluate the effect of land use and intrinsic soil properties on the risk of contamination with oocysts. Jackknife analysis revealed that the likelihood for positive results is significantly enhanced in soil originating from foci of human habitation, wood land and grass land. Furthermore, soil temperature and humidity significantly influence the probability of contamination with T. gondii oocysts. Our findings indicate that land use may affect distribution of T. gondii oocysts in urban areas. PMID- 27373379 TI - Evaluating the relationship between biotic and sediment metrics using mesocosms and field studies. AB - An ongoing research challenge is the detection of biological responses to elevated sediment and the identification of sediment-specific bioassessment metrics to evaluate these biological responses. Laboratory mesocosms and field observations in rivers in Ireland were used to evaluate the relationship between a range of biological and sediment metrics and to assess which biological metrics were best at discerning the effects of excess sediment on macroinvertebrates. Results from the mesocosm study indicated a marked decrease in the abundance of sensitive taxa with increasing sediment surface cover. % EPT (Ephemeroptera, Plecoptera, Trichoptera) and % E abundances exhibited the strongest negative correlation with sediment surface cover in the mesocosm study. The field study revealed that % EPT abundance was most closely correlated with % sediment surface cover, explaining 13% of the variance in the biological metric. Both studies revealed weaker relationships with a number of other taxonomy-based metrics including total taxon abundance, total taxon richness and moderate relationships with the Proportion of Sediment-sensitive Invertebrates metric (PSI). All trait based metrics were poorly correlated with sediment surface cover in the field study. In terms of sediment metrics, % surface cover was more closely related to biological metrics than either re-suspendable sediment or turbidity. These results indicate that % sediment surface cover and % EPT abundance may be useful metrics for assessing the effect of excessive sediment on macroinvertebrates. However, EPT metrics may not be specific to sediment impact and therefore when applied to rivers with multiple pressures should be combined with observations on sediment cover. PMID- 27373380 TI - Soil attributes and microclimate are important drivers of initial deadwood decay in sub-alpine Norway spruce forests. AB - Deadwood is known to significantly contribute to global terrestrial carbon stocks and carbon cycling, but its decay dynamics are still not thoroughly understood. Although the chemistry of deadwood has been studied as a function of decay stage in temperate to subalpine environments, it has generally not been related to time. We therefore studied the decay (mass of deadwood, cellulose and lignin) of equal-sized blocks of Picea abies wood in soil-mesocosms over two years in the Italian Alps. The 8 sites selected were along an altitudinal sequence, reflecting different climate zones. In addition, the effect of exposure (north- and south facing slopes) was taken into account. The decay dynamics of the mass of deadwood, cellulose and lignin were related to soil parameters (pH, soil texture, moisture, temperature) and climatic data. The decay rate constants of Picea abies deadwood were low (on average between 0.039 and 0.040y(-1)) and of lignin close to zero (or not detectable), while cellulose reacted much faster with average decay rate constants between 0.110 and 0.117y(-1). Our field experiments showed that local scale factors, such as soil parameters and topographic properties, influenced the decay process: higher soil moisture and clay content along with a lower pH seemed to accelerate wood decay. Interestingly, air temperature negatively correlated with decay rates or positively with the amount of wood components on south-facing sites. It exerted its influence rather on moisture availability, i.e. the lower the temperature the higher the moisture availability. Topographic features were also relevant with generally slower decay processes on south-facing sites than on north-facing sites owing to the drier conditions, the higher pH and the lower weathering state of the soils (less clay minerals). This study highlights the importance of a multifactorial consideration of edaphic parameters to unravel the complex dynamics of initial wood decay. PMID- 27373381 TI - Impact of liposomal amphotericin B therapy on chronic pulmonary aspergillosis. AB - OBJECTIVES: To assess the clinical response and renal toxicity observed in chronic pulmonary aspergillosis (CPA) patients receiving >=1 short-courses of liposomal amphotericin (LAmB) (AmBisome(r)) therapy. METHODS: A retrospective audit of clinical response and renal function was undertaken in 71 CPA patients (41 male) treated with LAmB at the National Aspergillosis Centre, including 20 patients receiving repeated treatment courses or long-term therapy (n = 5). RESULTS: Median age was 64 years (range 29-86 years). Treatment indications included respiratory symptoms (n = 33; 46.5%), constitutional symptoms (n = 2; 2.8%) or both (n = 36; 50.7%). 48 patients (73.8%) responded to their first LAmB course. Quality of life (QOL) improvements occurred in 37 (92.5%) of 40 patients with sufficient data available. Response rates for repeated short-courses of LAmB were 76.6%; QOL improvements were observed in 91.7% of treatment courses. All patients on long-term therapy demonstrated a response. 34 (50%) and 17 (25%) patients respectively developed an increased risk of acute kidney injury (AKI) or actual AKI with their first treatment; a significant reduction in geometric mean eGFR was observed and a similar pattern occurred following their second treatment course. CONCLUSIONS: Whilst CPA is responsive to LAmB, caution should be exercised with repeated courses, if other treatments are available. PMID- 27373382 TI - Corrigendum to "p65 down-regulates DEPTOR expression in response to LPS stimulation in hepatocytes" [Gene 589/1 (2016) 12-19]. PMID- 27373383 TI - Journal of Cataract & Refractive Surgery: 20 years on. PMID- 27373384 TI - Professor Jan Gerben Frans Worst. PMID- 27373385 TI - Facilitating cortical aspiration after insertion of a capsular tension ring. AB - We describe a simple, effective technique to prevent the cortical entrapment that can occur after a capsular tension ring (CTR) is implanted during phacoemulsification. Before the epinucleus has been removed, the blunt tip of an ophthalmic viscosurgical device (OVD) cannula is burrowed centrally in the cortical/epinuclear plate and OVD is injected as the cannula is advanced. The cannula is turned superiorly and dissection continued to the lens equator. The cleavage plane is extended for approximately 2 clock hours in the direction of the intended CTR insertion. The CTR is then inserted below the cortical/epinuclear plate. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27373386 TI - Femtosecond laser-assisted cataract surgery in complex cases. AB - PURPOSE: To describe the use of the femtosecond laser in complex cataract cases. SETTING: Department of Ophthalmology, University of Colorado, Aurora, Colorado, USA. DESIGN: Retrospective case series. METHODS: This was a single-center retrospective review of consecutive complex cataract surgery cases in which the Lensx femtosecond laser was used between October 2012 and February 2015. Complex cases were defined as white cataracts, dense brunescent cataracts, or cataracts in which zonulopathy was identified preoperatively. Outcome measures included an assessment of the capsulotomy, surgical complications, and postoperative corrected distance visual acuity (CDVA). RESULTS: Thirty-four eyes of 34 patients were included in this study; 27 had white cataract, 3 had dense brunescent cataract, and 6 had zonulopathy (2 of these also had white cataract). Three patients had an incomplete capsulotomy, and 3 had small radial tears in the anterior capsule. Four patients (11.7%) developed posterior capsule tears during phacoemulsification; 1 of these subsequently had pars plana vitrectomy for a retained lens fragment. Twenty-eight (97%) of 29 patients had a postoperative CDVA of 20/40 or better. Three patients were identified with comorbidities that limited postoperative CDVA. One patient developed postoperative cystoid macular edema. CONCLUSION: The femtosecond laser was useful in the surgical approach to patients with complex cataracts, especially for the creation of the capsulotomy. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27373387 TI - Intraoperative aberrometry versus standard preoperative biometry and a toric IOL calculator for bilateral toric IOL implantation with a femtosecond laser: One month results. AB - PURPOSE: To compare astigmatic outcomes in patients with bilateral cataracts having toric intraocular lens (IOL) implantation with intraoperative aberrometry measurements in 1 eye and standard power calculation and a toric IOL calculator with inked axis marking in the contralateral eye. SETTING: Twelve sites in the United States. DESIGN: Prospective cohort study. METHODS: The eye with the more visually significant cataract was randomized to intraoperative aberrometry measurements (Ocular Response Analyzer with Verifeye) or standard preoperative biometry and use of a toric calculator with the contralateral eye automatically assigned to the other group. The primary effectiveness outcome was the proportion of eyes with a postoperative refractive astigmatism of 0.50 diopter (D) or less at 1 month. RESULTS: Of the 130 patients (260 eyes) enrolled, 124 (248 eyes) were randomized; 121 (242 eyes) completed the trial. The percentage of eyes with astigmatism of 0.50 D or less at 1 month was higher in the intraoperative aberrometry group than in the standard group (89.2% versus 76.6%) (P = .006). The mean postoperative refractive astigmatism was lower in the intraoperative aberrometry group (0.29 D +/- 0.28 [SD] versus 0.36 +/- 0.35 D) (P = .041). Secondary effectiveness endpoints, including manifest refraction spherical equivalent prediction error, uncorrected distance visual acuity, and corrected distance visual acuity, were similar. CONCLUSIONS: Compared with standard methods, the use of the intraoperative aberrometry system increased the proportion of eyes with postoperative refractive astigmatism of 0.50 D or less and reduced the mean postoperative refractive astigmatism at 1 month. Other efficacy outcomes were similar. FINANCIAL DISCLOSURES: Drs. Woodcock, Lehmann, and Cionni are consultants to Alcon Laboratories, Inc. Dr. Breen is an employee of Alcon Laboratories, Inc. Dr. Scott has no financial or proprietary interest in any material or method mentioned. PMID- 27373388 TI - Anterior capsule opacification after femtosecond laser-assisted cataract surgery: Clinical classification versus Scheimpflug device densitometry values. AB - PURPOSE: To compare the clinical classification of anterior capsule opacification (ACO) after femtosecond laser-assisted cataract surgery with the mean density values of ACO provided by rotating Scheimpflug device (Pentacam HR) densitometry software and to determine which densitometry method correlates best with the clinical classification. SETTING: Ophthalmology Department, Donostia University Hospital, Donostia-San Sebastian, Spain. DESIGN: Prospective comparative study. METHODS: Femtosecond laser-assisted cataract surgery was performed using the Victus platform between June 2014 and March 2015. Inclusion criteria were age between 55 years and 85 years, a pupil diameter larger than 6.0 mm in full mydriasis, no intraoperative complications, a curvilinear anterior capsulotomy without tears, and an intraocular lens in the correct intracapsular position at the end surgery. The ACO was measured by a clinical classification ranging from 0 to 4. In addition, ACO density was measured with the Scheimpflug device using 3 densitometry methods (area, linear, and peak). RESULTS: The study comprised 32 eyes of 32 patients. Area and linear densitometry values provided by the Scheimpflug device had a strong correlation with the values obtained by clinical classification, whereas peak densitometry values had a very weak correlation at 6 months (area densitometry: Spearman rho = 0.78; P < .0005; linear densitometry: rho = 0.73; P < .0005; peak densitometry rho = 0.21; P = .2). CONCLUSION: The Scheimpflug device provided an objective measurement of ACO after cataract surgery. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27373389 TI - Cataract surgery in patients with chronic severe graft-versus-host disease. AB - PURPOSE: To evaluate the surgical outcomes of cataract extraction with phacoemulsification and intraocular lens implantation in patients with severe chronic ocular graft-versus-host disease (GVHD). SETTING: University of South Florida Eye Institute, Tampa, Florida, USA. DESIGN: Retrospective case study. METHODS: A chart review was performed to identify patients with clinically severe, biopsy-proven chronic ocular GVHD who had cataract extraction. Outcome parameters included preoperative and postoperative corrected distance visual acuity (CDVA), type of cataract, postoperative complications, type of underlying malignancy, and time from bone marrow transplant to cataract extraction. RESULTS: This study comprised 10 eyes of 6 patients with severe GVHD. Posterior subcapsular cataract accounted for all cataracts that were surgically removed in this patient cohort. The mean preoperative CDVA was 20/84, which improved to 20/30 at the 1-month postoperative visit and remained stable at 20/28 at the final visit noted in the charts (both P < .05). Two patients developed postoperative corneal melting. All but 1 patient had improved visual acuity after surgery. CONCLUSIONS: With meticulous preoperative biometric measurements and calculations and aggressive assessment and treatment of dry-eye syndrome, patients with severe ocular GVHD who had cataract extraction had excellent postsurgical refractive outcomes. Postoperative corneal melting was a complication seen with greater frequency than anticipated in this patient cohort. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27373390 TI - Refractive outcomes after phacovitrectomy surgery. AB - PURPOSE: To evaluate the refractive accuracy of intraocular lens (IOL) power calculation after phacovitrectomy. SETTING: Eye Hospital Zonnestraal and Department of Ophthalmology Academic Medical Center, Amsterdam, the Netherlands. DESIGN: Retrospective comparative case series. METHODS: Refraction results 1 month after phacovitrectomy or phacoemulsification were compared with predicted refractions calculated using the IOLMaster 500 and the Haigis formula. Indications for vitrectomy were macular pucker, macular hole, vitreous floaters, vitreous hemorrhage, and vitreomacular traction. Enrolled eyes had an axial length (AL) between 20.13 mm and 29.43 mm. RESULTS: The phacovitrectomy group comprised 133 eyes (133 patients) and the phacoemulsification group, 132 eyes (132 patients). The refractive outcomes after phacovitrectomy (-0.06 diopter [D] +/- 0.50 [SD]) and phacoemulsification (-0.08 +/- 0.47 D) were comparable (P = .74). The final postoperative refraction was within +/-1.00 D of the preoperative refractive target in 94.9% and 94.6% of phacovitrectomy cases and phacoemulsification cases, respectively. Subgroup analysis found no increased risk for refractive surprises after gas tamponade or in eyes with an AL of 26.00 mm or greater. CONCLUSIONS: Standard IOL power calculation used in regular phacoemulsification surgery was accurate in phacovitrectomy procedures in eyes with a wide range of AL and a wide range of vitrectomy indications. No tendency toward a myopic shift was found. FINANCIAL DISCLOSURE: Dr. Lapid-Gortzak is a clinical investigator for, speaker for, and consultant to Alcon Laboratories, Inc., Hanita Lenses, a speaker for Santen Pharmaceutical Co., and a consultant to Sanoculis and Orca Surgical. None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27373391 TI - Descemet-stripping automated endothelial keratoplasty in eyes with transscleral sutured intraocular lenses. AB - PURPOSE: To compare the clinical outcomes and complications of Descemet-stripping automated endothelial keratoplasty (DSAEK) with a transscleral-sutured intraocular lens (IOL) and solitary DSAEK. SETTING: Department of Ophthalmology, Tokyo Dental College, Chiba, Japan. DESIGN: Retrospective case series. METHODS: Cases with simultaneous transscleral-sutured IOLs or post-transscleral-sutured IOLs and solitary DSAEK cases were studied. The logMAR acuity, astigmatism, endothelial cell density (ECD), graft survival rate, and complications (eg, IOL dislocation, cystoid macular edema [CME]) were analyzed. RESULTS: Thirty-seven DSAEK cases with simultaneous transscleral-sutured IOLs or post-transscleral sutured IOLs and 147 solitary DSAEK cases were evaluated. The logMAR corrected distance visual acuity (CDVA) improved significantly at 24 months, from 1.34 +/- 0.49 (SD) to 0.48 +/- 0.38 after DSAEK with transscleral-sutured IOLs and from 1.17 +/- 0.69 to 0.17 +/- 0.25 after solitary DSAEK. The logMAR CDVA after DSAEK with transscleral-sutured IOLs was significantly worse than that with solitary DSAEK at 6, 12, and 24 months (P < .01). The postoperative astigmatism with DSAEK with transscleral-sutured IOLs was significantly higher than with solitary DSAEK because of the larger sclerocorneal incision (P < .02). There were no significant differences in ECD or graft survival rates between DSAEK with transscleral sutured IOLs and solitary DSAEK. The incidence of CME in DSAEK with transscleral sutured IOLs (4/37 eyes [11%]) was higher than with solitary DSAEK (2/147 [1.4%]) (P = .02). The CME resolved with topical diclofenac and sub-Tenon injection of triamcinolone acetonide in all eyes. CONCLUSION: The graft survival rates after DSAEK with transscleral-sutured IOLs were equivalent to those after solitary DSAEK, although the incidence of CME was higher than after solitary DSAEK. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27373392 TI - Standardized approach to training for cataract surgery skill evaluation. AB - PURPOSE: To assess interrater reliability in grading cataract surgery performance of ophthalmology residents and attending physicians before and after rater skill training. SETTING: Metropolitan Chicago, Illinois, USA. DESIGN: Prospective interventional test design. METHODS: Video versions of a previously validated scoring key for rating cataract surgery were created for participant training. All participants received 2 frame-of-reference training sessions lasting 2 hours each. Participants graded 4 videorecorded cataract surgeries before training (pretest) and 4 more after training (posttest). Intraclass correlation coefficients (ICCs), which measured the degree of rater agreement, were calculated before and after training. Participants completed a subjective confidence questionnaire at the beginning and at the end of the study. RESULTS: The study participants included 9 postgraduate year (PGY)-3 residents, 8 PGY-4 residents, and 5 ophthalmology attending physicians from 4 medical centers in metropolitan Chicago. The rater training sessions had the greatest increase in ICCs among PGY-3 residents. The ICC improvement between the PGY-4 residents and attending physicians was uneven. After training, all residents felt more confident about their ability to rate and to perform cataract surgery. CONCLUSIONS: Learning to effectively grade performance of cataract surgery by reviewing video clips has the potential to be an important part of ophthalmology residency education. The benefit of such a protocol was greatest in the early stages of residency education and might provide a guideline for quality assessment that accelerates surgical skill development. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27373393 TI - Change in light scattering caused by glistenings in hydrophobic acrylic intraocular lenses from 10 to 15 years after surgery. AB - PURPOSE: To analyze the long-term change in light scattering caused by glistenings in hydrophobic acrylic intraocular lenses (IOLs) and the clinical implications on high-contrast and low-contrast visual acuity. SETTING: Department of Clinical Sciences/Ophthalmology, Umea University Hospital, Umea, Sweden. DESIGN: Prospective longitudinal case series. METHODS: The study comprised patients who had an Acrysof MA60BM IOL implanted between 1997 and 1998. Light scattering from the IOLs was assessed with digital analysis using Scheimpflug photography (Pentacam HR) from both the 10- year and 15-year follow-up. Associations were made between corrected distance visual acuity, low-contrast visual acuity (LCVA) 10.0%, LCVA 2.5%, and the degree of light scattering from the IOL. RESULTS: At the 15-year follow-up, the majority of the 90 patients had an increased amount of light scattering in all parts measured in the IOL than the patients at the 10-year follow-up. A subgroup of 71 patients without coexisting ocular pathology was selected for the visual function analyses. There was no correlation between light scattering and dioptric power. No clinically relevant reduction in visual function was detected in eyes with more pronounced light scattering. Patients with a larger increase in total light scattering of the IOL at the 15-year follow-up had significantly worse LCVA 2.5% than at the 10-year follow-up (P = .042). CONCLUSIONS: Glistenings continued to increase in hydrophobic acrylic IOLs from 10 to 15 years after surgery. At 15 years, most patients had severe glistenings with a high level of light scattering from the IOL. No clinically significant effect on everyday visual function was found. FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in any material or method mentioned. PMID- 27373394 TI - Outcomes of implantation of modified capsule tension rings with multiple black occluder paddles for eyes with congenital and acquired iris defects: Report 3. AB - PURPOSE: To evaluate the safety and efficacy of Morcher 50F iris diaphragm implantation to manage moderate to large defects of the human iris. SETTING: Stein Eye Institute, UCLA, Los Angeles, California, USA. DESIGN: Prospective nonrandomized interventional case series. METHODS: The demographic, preoperative, and postoperative data of patients who had implantation of modified capsular tension rings and followed to 1 year were reviewed. Safety measures included loss of corrected distance visual acuity (CDVA), surgical complications, adverse events, and secondary surgical interventions. Efficacy measures included CDVA with glare, daytime and nighttime glare symptom scores, and subjective cosmesis scores. RESULTS: The study comprised 12 patients. The median CDVA was 20/70 before surgery and 20/20 after surgery. There were no lost lines of CDVA and no intraoperative complications. The most common postoperative complication was posterior capsule opacification. Two adverse events were unrelated to the device. Four patients had secondary surgical interventions, the most common of which was laser capsulotomy. The median CDVA with glare improved from less than 20/400 before surgery to 20/50 after surgery. One patient worsened. The median subjective daytime glare symptom score improved from 9 to 3 on a 10-point scale (P = .001). The median nighttime subjective glare symptom score improved from 8 to 2 (P = .001). The subjective cosmetic appearance of the eye stayed the same or improved for all patients (P = .031). CONCLUSION: Iris diaphragm implantation was relatively safe and effective for reducing light and glare sensitivity in eyes with iris defects when combined with cataract extraction and intraocular lens implantation. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27373395 TI - Patient-reported outcomes 5 years after laser in situ keratomileusis. AB - PURPOSE: To assess vision-related, quality-of-life outcomes 5 years after laser in situ keratomileusis (LASIK) and determine factors predictive of patient satisfaction. SETTING: Optical Express, Glasgow, Scotland. DESIGN: Retrospective case series. METHODS: Data from patients who had attended a clinical examination 5 years after LASIK were analyzed. All treatments were performed using the Visx Star S4 IR excimer laser. Patient-reported satisfaction, the effect of eyesight on various activities, visual phenomena, and ocular discomfort were evaluated 5 years postoperatively. Multivariate regression analysis was performed to determine factors affecting patient satisfaction. RESULTS: The study comprised 2530 patients (4937 eyes) who had LASIK. The mean age at the time of surgery was 42.4 years +/- 12.5 (SD), and the preoperative manifest spherical equivalent ranged from -11.0 diopters (D) to +4.88 D. Five years postoperatively, 79.3% of eyes were within +/-0.50 D of emmetropia and 77.7% of eyes achieved monocular uncorrected distance visual acuity (UDVA) and 90.6% of eyes achieved binocular UDVA of 20/20 or better. Of the patients, 91.0% said they were satisfied with their vision and 94.9% did not wear distance correction. Less than 2.0% of patients noticed visual phenomena, even with spectacle correction. Major predictors of patient satisfaction 5 years postoperatively were postoperative binocular UDVA (37.6% variance explained by regression model), visual phenomena (relative contribution of 15.0%), preoperative and postoperative sphere and their interactions (11.6%), and eyesight-related difficulties with various activities such as night driving, outdoor activities, and reading (10.2%). CONCLUSION: Patient-reported quality-of-life and satisfaction rates remained high 5 years after LASIK. Uncorrected vision was the strongest predictor of satisfaction. FINANCIAL DISCLOSURE: Dr. S.C. Schallhorn is a consultant to Abbott Medical Optics, Inc., Zeiss Meditec AG, and Autofocus Inc. and a global medical director for Optical Express. No other author has a financial or proprietary interest in any material or method mentioned. PMID- 27373397 TI - Changes in stereopsis after photorefractive keratectomy. AB - PURPOSE: To evaluate the effects of photorefractive keratectomy (PRK) on the stereopsis of myopic and hyperopic patients. SETTING: Farabi Eye Hospital, Tehran, Iran. DESIGN: Prospective case series. METHODS: This study included patients having PRK to achieve emmetropia. The patients were divided into the following 3 groups: low myopia (<-6.0 diopters [D]), high myopia (>-6.0 D), and hyperopia (<+4.0 D). Near stereoacuity was measured using the Randot test under photopic conditions (with corrective glasses) at 40 cm preoperatively (with corrective glasses) and 1, 3, and 12 months postoperatively. Repeated-measure analysis of variance was used to assess changes in stereopsis over time in the 3 groups. RESULTS: Each group comprised 60 patients. The mean preoperative stereoacuity was 121.16 seconds of arc (arcsec) +/- 149.92 (SD), improving to 83.66 +/- 75.84 arcsec 1 month postoperatively and 80.66 +/- 64.31 arcsec at 3 months (both P < .001). It remained unchanged (83.33 +/- 75.01 arcsec) at 12 months (P = .610). Patients with high myopia had the greatest improvement in stereopsis after PRK compared with low myopic and hyperopic patients (P < .001). The improvement in stereoacuity was significantly higher in the severe anisometropic group; the lowest improvement was in the group without anisometropia. CONCLUSION: Photorefractive keratectomy could result in an improvement in stereopsis. Patients with high myopia benefitted most from PRK in terms of improvement in stereopsis. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27373396 TI - Photorefractive keratectomy combined with corneal wavefront-guided and hyperaspheric ablation profiles to correct myopia. AB - PURPOSE: To evaluate the effects of photorefractive keratectomy (PRK) combined with corneal wavefront-guided ablation profiles and hyperaspheric ablation profiles on changes in higher-order aberrations (HOAs). SETTING: Yonsei University College of Medicine and Eyereum Clinic, Seoul, South Korea. DESIGN: Comparative observational case series. METHODS: Medical records of patients who had corneal wavefront-guided hyperaspheric PRK, corneal wavefront-guided mild aspheric PRK, or non-corneal wavefront-guided mild-aspheric PRK were analyzed. The logMAR uncorrected distance visual acuity (UDVA), manifest refraction spherical equivalent (MRSE), and changes in corneal aberrations (root-mean-square [RMS] HOAs, spherical aberration, coma) were evaluated 1, 3, and 6 months postoperatively. RESULTS: The records of 61 patients (96 eyes) were reviewed. There was no statistically significant difference in logMAR UDVA or MRSE between the 3 groups at any timepoint. Corneal RMS HOAs were significantly smaller in the corneal wavefront-guided hyperaspheric group and the corneal wavefront-guided mild-aspheric group than in the noncorneal wavefront-guided mild-aspheric group at each timepoint. Corneal spherical aberration was significantly smaller for corneal wavefront-guided hyperaspheric PRK than for noncorneal wavefront-guided mild-aspheric PRK 6 months postoperatively. Changes in corneal spherical aberration (preoperatively and 6 months postoperatively) in corneal wavefront guided hyperaspheric PRK were significantly smaller than in corneal wavefront guided mild-aspheric PRK (P = .046). Corneal coma was significantly smaller with corneal wavefront-guided hyperaspheric PRK and corneal wavefront-guided mild aspheric PRK than with noncorneal wavefront-guided mild-aspheric PRK 3 months and 6 months postoperatively. CONCLUSION: Corneal wavefront-guided hyperaspheric PRK induced less corneal spherical aberration 6 months postoperatively than corneal wavefront-guided mild-aspheric PRK and noncorneal wavefront-guided mild-aspheric PRK. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27373398 TI - Comparability of an image-guided system with other instruments in measuring corneal keratometry and astigmatism. AB - PURPOSE: To test whether keratometry (K) and astigmatism measurements provided by the Verion Reference Unit (an image-guided system) compared well with the Tonoref II automated tonometer-refractometer, IOLMaster partial coherence interferometry (PCI) biometer, AL-Scan optical biometer, Pentacam rotating Scheimpflug camera, and OPD Scan III wavefront aberrometer. SETTING: Augenklinik am Neumarkt, Cologne, Germany. DESIGN: Retrospective case series. METHODS: Patients having routine cataract surgery had standard preoperative assessment including biometry measurement with all study devices. The K values, power of astigmatism, axis, and the lens power of an imaginary intraocular lens (IOL) were analyzed for each device. RESULTS: One hundred five eyes of 62 patients with a mean age of 68.5 years +/- 11.9 (SD) (range 27.2 to 89.7 years) were included in the study. The mean differences in flat K readings between the image-guided system and the tonometer-refractometer, PCI biometer, optical biometer (2.4 and 3.2 mm), rotating Scheimpflug camera, and wavefront aberrometer were -0.03 mm, 0.00 mm, 0.01 mm (both 2.4 and 3.2 mm), -0.03 mm, and -0.01 mm, respectively (P < .001). Differences were slightly greater for steep K readings as follows: -0.04 mm, 0.01 mm, -0.02 (optical biometer 2.4 mm), -0.03 mm (optical biometer 3.2 mm), 0.04 mm, and -0.06 mm, respectively (P < .001). The calculated power of an imaginary IOL from the study devices fell within 0.28 diopter of one another (P > .05). CONCLUSIONS: The image-guided system compared well with and provided astigmatism measurements similar to those of currently available diagnostic measurement devices. This system can aid appropriate preoperative IOL power calculations. FINANCIAL DISCLOSURES: Drs. Schultz, Oberheide, and Kermani have received honoraria from Alcon Pharma GmbH for corporate presentations. PMID- 27373399 TI - Immunomodulatory therapy with anti-interleukin-1 after photorefractive keratectomy in the New Zealand white rabbit. AB - PURPOSE: To examine the safety and efficacy of topical anti-interleukin-1 (anti IL-1) following photorefractive keratectomy (PRK) in rabbit eyes. SETTING: Joint Warfighter Refractive Surgery Center, Lackland Air Force Base, Texas, USA. DESIGN: Experimental study. METHODS: After standard PRK, 48 eyes of 24 New Zealand white rabbits were divided into 4 treatment arms and 1 control arm. Eyes in the treatment arms were randomized to receive fluorometholone 0.1% or an anti IL-1 suspension (2.50 mg, 1.25 mg, or 0.25 mg doses) plus standard moxifloxacin, balanced salt solution (BSS), and an ocular lubricant (Systane) 4 times a day. Control eyes received only moxifloxacin, balanced salt solution, and ocular lubricant. RESULTS: No adverse events were observed with anti-IL-1. The safety of anti-IL-1 was affirmed because there was no statistically significant difference in time to epithelial closure, foam-layer histology and thickness, or final stromal thickness measurements between the anti-IL-1 and the steroid or control groups. No increase in haze was observed with anti-IL-1. There was a trend toward decreased haze with anti-IL-1 at several data points compared with the control and steroid groups. Finally, there was a trend toward less haze in all metrics at almost every timepoint for the 2.50 mg anti-IL-1 group compared with lesser concentrations. CONCLUSIONS: Anti-IL-1 therapy might be a safe, effective alternative to steroids for haze prevention after PRK. Of the doses studied, 2.50 mg of anti-IL-1 4 times a day appeared to be most effective. Further studies in human eyes are needed. FINANCIAL DISCLOSURE: Dr. Reilly has been a consultant to Alcon Laboratories, Inc., and Abbott Medical Optics, Inc. None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27373400 TI - Surgical correction of presbyopia. AB - Presbyopia is the most common refractive disorder for people older than 40 years. It is characterized by a gradual and progressive decrease in accommodative amplitude. Many surgical procedures for the correction of presbyopia exist, with additional procedures on the horizon. This review describes the prevalent theories of presbyopia and discusses the available surgical options for correction. FINANCIAL DISCLOSURE: Proprietary or commercial disclosures are listed after the references. PMID- 27373402 TI - Inaccurate use of sign/symbol to represent corneal astigmatism. PMID- 27373401 TI - Late-onset, snowstorm-like appearance of calcium deposits coating a poly(methyl methacrylate) posterior chamber intraocular lens. AB - An 81-year-old man developed decreased vision associated with diffuse precipitates on his poly(methyl methacrylate) (PMMA) posterior chamber intraocular lens (IOL), on his corneal endothelium, and in his anterior chamber approximately 35 years after IOL implantation. Slitlamp evaluation showed diffuse white material on the surface of the IOL, white precipitates on the corneal endothelium, and visible debris in the anterior chamber. The patient had IOL exchange, and pathological analysis showed numerous calcium deposits within the Soemmerring ring that diffusely spread to the anterior surface of the PMMA IOL. This case of diffuse calcium precipitates on the IOL and the corneal endothelium and in the anterior chamber 35 years after implantation shows that even long after IOL implantation, lens epithelium proliferation and metabolism can result in sequestered material that can be released many years later. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27373403 TI - Long-term outcomes of cataract surgery: 15-year results of a prospective study. PMID- 27373404 TI - Safety of intracameral phenylephrine. PMID- 27373405 TI - Reply. PMID- 27373406 TI - Intraocular lens placement with inadequate capsule support. PMID- 27373408 TI - Reply. PMID- 27373407 TI - Cystoid macular edema after femtosecond laser-assisted versus phacoemulsification cataract surgery: Letter 1. PMID- 27373409 TI - Cystoid macular edema after femtosecond laser-assisted versus phacoemulsification cataract surgery: Letter 2. PMID- 27373411 TI - Erratum. PMID- 27373410 TI - Reply. PMID- 27373412 TI - Erratum. PMID- 27373413 TI - Repressed PKCdelta activation in glycodelin-expressing cells mediates resistance to phorbol ester and TGFbeta. AB - Glycodelin is a glycoprotein mainly expressed in well-differentiated epithelial cells in reproductive tissues. In normal secretory endometrium, the expression of glycodelin is abundant and regulated by progesterone. In hormone-related cancers glycodelin expression is associated with well-differentiated tumors. We have previously found that glycodelin drives epithelial differentiation of HEC-1B endometrial adenocarcinoma cells, resulting in reduced tumor growth in a preclinical mouse model. Here we show that glycodelin-transfected HEC-1B cells have repressed protein kinase C delta (PKCdelta) activation, likely due to downregulation of PDK1, and are resistant to phenotypic change and enhanced migration induced by phorbol 12-myristate 13-acetate (PMA). In control cells, which do not express glycodelin, the effects of PMA were abolished by using PKCdelta and PDK1 inhibitors, and knockdown of PKCdelta, MEK1 and 2, or ERK1 and 2 by siRNAs. Similarly, transforming growth factor beta (TGFbeta)-induced phenotypic change was only seen in control cells, not in glycodelin-producing cells, and it was mediated by PKCdelta. Taken together, these results strongly suggest that PKCdelta, via MAPK pathway, is involved in the glycodelin-driven cell differentiation rendering the cells resistant to stimulation by PMA and TGFbeta. PMID- 27373414 TI - Microvascular Decompression for Trigeminal Neuralgia: Technical Refinement for Complication Avoidance. AB - BACKGROUND: Microvascular decompression (MVD) represents the most effective and safe surgical option for the treatment of trigeminal neuralgia since it was first popularized by Jannetta 50 years ago. Despite several advances, complications such as cerebellar and vascular injury, hearing loss, muscular atrophy, cerebrospinal fluid (CSF) leak, postoperative cutaneous pain, and sensory disturbances still occur and may negatively affect the outcome. We propose some technical nuances of the surgical procedure that were used in our recent series. METHODS: We used a novel hockey stick-shaped retromastoid skin incision, preserving the major nerves of the occipital and temporal areas. Microsurgical steps were performed without the use of retractors. CSF leakage was prevented with a watertight dural closure and multilayer osteodural reconstruction. RESULTS: The refined surgical steps were perfected in the last consecutive 15 cases of our series. In these cases we did not record any cutaneous pain, sensory disturbances, or CSF leakage. The average diameter of the craniectomy was 18 mm. No patient reported major complications related to the intradural microsurgical maneuvers. In all cases the neurovascular conflict was found and solved with a good outcome in terms of pain disappearance. CONCLUSIONS: Our minimally invasive approach was demonstrated to guarantee an optimal exposure of the cerebellopontine angle and minimize the rate of complications related to skin incision and muscular dissection, microsurgical steps, and closure. PMID- 27373415 TI - Treatment Strategies to Attenuate Perihematomal Edema in Patients With Intracerebral Hemorrhage. AB - Spontaneous intracerebral hemorrhage (SICH) continues to be a significant cause of neurologic morbidity and mortality throughout the world. Although recent advances in the treatment of SICH have significantly decreased mortality rates, functional recovery has not been dramatically improved by any intervention to date. There are 2 predominant mechanisms of brain injury from intracerebral hemorrhage: mechanical injury from the primary hematoma (including growth of that hematoma), and secondary injury from perihematomal inflammation. For instance, in the hours to weeks after SICH as the hematoma is being degraded, thrombin and iron are released and can result in neurotoxicity, free radical damage, dysregulated coagulation, and harmful inflammatory cascades; this can clinically and radiologically manifest as perihematomal edema (PHE). PHE can contribute to mass effect, cause acute neurologic deterioration in patients, and has even been associated with poor long-term functional outcomes. PHE therefore lends itself to being a potential therapeutic target. In this article, we will review 1) the pathogenesis and time course of the development of PHE, and 2) the clinical series and trials exploring various methods, with a focus on minimally invasive surgical techniques, to reduce PHE and minimize secondary brain injury. Promising areas of continued research also will be discussed. PMID- 27373416 TI - Gamma Knife Surgery for Cavernous Sinus Hemanginoma: A Report of 32 Cases. AB - BACKGROUND: Cavernous sinus hemangioma (CSH) is a rare type of benign vascular tumor. Microsurgery for CSH treatment usually results in profuse bleeding and cranial nerve injury. Radiosurgery is an alternative treatment for CSH. The objective of this study was to elucidate the efficacy and safety of gamma knife surgery (GKS) for the treatment of CSH. METHODS: A total of 32 patients with CSH underwent 34 times of GKS as a primary and exclusive treatment from 2009 to 2015 at West China Hospital. The diagnosis was mainly based on findings of magnetic resonance imaging. The treatment was performed with the Leksell Gamma Knife model C. The follow-up period was from 12-67 months. Changes in imaging results and signs or symptoms were analyzed. Studies of patients who had undergone radiosurgery and microsurgery were compared. RESULTS: Clinical improvement was observed after GKS in 26 of 27 patients who presented with signs or symptoms of CSH. Tumor shrinkage was detected in all cases. A reduction in tumor volume of 0 25%, 26%-50%, 51%-75%, and 76%-100% was observed in 3, 2, 8, and 19 cases, respectively. Remarkable tumor shrinkage occurred within 6-12 months after GKS. According to a retrospective analysis of 151 patients diagnosed with CSH, 77 patients underwent GKS without any complications, 17 of 74 patients were treated with microsurgery and exhibited persistent complications, and 1 patient died. CONCLUSIONS: GKS is a safe and effective treatment for most cases of CSH. The concept of GKS as an adjuvant treatment for CSH requires reconsideration. PMID- 27373417 TI - Postoperative Morbidity and Mortality After Elective Anterior Cervical Fusion in Patients with Chronic and End-Stage Renal Disease. AB - OBJECTIVE: We sought to investigate the postoperative morbidity and mortality rate of patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) undergoing elective anterior cervical fusion (ACF). METHODS: The Nationwide Inpatient Sample database from 2002-2011 was used to identify adult patients who underwent elective ACF for degenerative spine disease. Major complication rates and in-hospital mortality were compared among 3 groups-no kidney disease, CKD, and ESRD (dialysis dependent). A multiple logistic regression analysis was conducted to assess the independent effect of CKD and ESRD on outcome. RESULTS: There were 164,097 patients who met inclusion criteria. Among these, 1047 had CKD (0.64%) and 270 had ESRD (0.16%). After multiple logistic regression analysis, patients with CKD (odds ratio [OR] 1.51; 95% confidence interval [CI], 1.13-2.01; P = 0.005) and ESRD (OR 1.96; 95% CI, 1.20 3.21; P = 0.007) were significantly more likely to incur a postoperative complication when compared with patients without kidney disease (the reference group). Compared with patients without kidney disease, patients with CKD did not have higher odds of postoperative mortality (OR 2.25; 95% CI, 0.83-6.06; P = 0.108). However, in-hospital mortality was 15 times higher for patients with ESRD compared with patients without kidney disease (OR 15.2; 95% CI, 5.67-40.88; P < 0.001). CONCLUSION: Chronic and end-stage renal disease may significantly increase the risk of postoperative morbidity and mortality after ACF. Future research into preoperative optimization of these patients and on the potential benefits of undergoing surgery until after renal transplantation is warranted. PMID- 27373418 TI - Stereo-electro-encephalography-Guided Radiofrequency Thermocoagulation: From In Vitro and In Vivo Data to Technical Guidelines. AB - BACKGROUND: Deep brain electrodes have been used for the past 10 years to produce bipolar stereo-electro-encephalography-guided radiofrequency thermocoagulation (SEEG RF-TC). However, this technique is based on empiric knowledge. The aim of this study is 3-fold: 1) provide in vivo animal data concerning the effect of bipolar RF-TC on brain and its safety; 2) assess the parameters of this procedure (current delivery and dipole selection) that produce the most efficient lesion; and 3) provide technical guidelines. METHODS: First we achieved in vivo RF-TC on rabbit brains with several conditions (power delivered and lesioning duration) and analyzed their influence on the lesion produced. Only a difference in terms of volume was found, and type of histologic lesions was similar whatever the settings were. We then performed multiple RF-TC in vitro on egg albumen, first with several parameters of radiofrequency and then with different dipole spatial selections. The end point was the size of the radiofrequency thermolesion produced. RESULTS: Using unfixed parameters of radiofrequency current delivery and increasing it until the power delivered by the generator collapsed produced significantly larger lesions (P = 0.008) than other conditions. Concerning the dipole selection, the use of contiguous contacts on electrodes led to lesions with a higher volume (P = 7.7 * 10-13) than those produced with noncontiguous ones. CONCLUSION: Besides the target selection in SEEG RF-TC, which is summarized on the basis of a literature review, we report the optimal parameters: Radiofrequency current must be increased until the power delivered collapses, and dipoles should be constituted by contiguous electrode contacts. PMID- 27373419 TI - Signaling mechanisms underlying the glioprotective effects of resveratrol against mitochondrial dysfunction. AB - Resveratrol, a polyphenol found in grapes and red wine, exhibits antioxidant, anti-inflammatory, anti-aging and, neuroprotective effects. Resveratrol also plays a significant role modulating glial functionality, protecting the health of neuroglial cells against several neuropsychiatric in vivo and in vitro experimental models. Mitochondrial impairment strongly affected astrocyte functions and consequently brain homeostasis. Molecules that promote astrocyte mitochondrial protection are fundamental to maintain brain energy balance and cellular redox state, contributing to brain healthy. Thus, the present study was designed to evaluate some glioprotective mechanisms of resveratrol against mitochondrial damage promoted by azide exposure in hippocampal primary astrocyte cultures. Azide treatment provoked deleterious effects, including the dysfunction of mitochondria, the deterioration of redox homeostasis, the augmentation of pro inflammatory cytokines and impairment of glutamate uptake activity. However, resveratrol prevented these effects, protecting hippocampal astrocytes against azide-induced cytotoxicity through the heme-oxygenase-1 (HO-1) pathway and inhibiting p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor kappa B (NFkappaB) activation. Resveratrol also protected astrocytes via phosphatidylinositide 3-kinase (PI3K)/Akt. These results contribute to the comprehension of the mechanisms by which resveratrol mediates hippocampal astrocyte protection against mitochondrial failure and implicate resveratrol as an important glioprotective molecule. PMID- 27373420 TI - Rejection of adenovirus infection is independent of coxsackie and adenovirus receptor expression in cisplatin-resistant human lung cancer cells. AB - The adenovirus vector-based cancer gene therapy is controversial. Low transduction efficacy is believed to be one of the main barriers for the decreased expression of coxsackie and adenovirus receptor (CAR) on tumor cells. However, the expression of CAR on primary tumor tissue and tumor tissue survived from treatment has still been not extensively studied. The present study analyzed the adenovirus infection rates and CAR expression in human lung adenocarcinoma cell line A549 and its cisplatin-resistant subline A549/DDP. The results showed that although the CAR expression in A549 and A549/DDP was not different, compared with the A549, A549/DDP appeared obviously to reject adenovirus infection. Moreover, we modified CAR expression in the two cell lines with proteasome inhibitor MG-132 and histone deacetylase inhibitor trichostatin A (TSA), and analyzed the adenovirus infection rates after modifying agent treatments. Both TSA and MG-132 pretreatments could increase the CAR expression in the two cell lines, but the drug pretreatments could only make A549 cells more susceptible to adenovirus infectivity. PMID- 27373421 TI - Comparative Analysis of Lipid Content and Fatty Acid Composition of Commercially Important Fish and Shellfish from Sri Lanka and Japan. AB - Sri Lanka is surrounded by the Indian Ocean, allowing plenty of fishes to be caught. Moreover, these fishes represent one of the undocumented fish resources in the world and their detailed lipid profiles have not been previously examined. In this study, the lipid content and fatty acid composition of 50 commercially important fishes from the Indian Ocean (Sri Lanka) and the Pacific Ocean (Japan) were compared. The total lipid content and fatty acid composition, including eicosapentaenoic acid (C20:5n-3, EPA) and docosahexaenoic acid (C22:6n-3, DHA), differed significantly among species. Fish from the Pacific Ocean had higher proportions of fatty acids, including EPA and DHA. Herrings and mackerels from both oceanic areas demonstrated high levels of EPA and DHA, and n-3/n-6 ratio. Brackish and freshwater fishes from both groups showed low levels of PUFAs. Fish from the Indian Ocean were high in n-6 fatty acids. Monounsaturated fatty acid levels were high in omnivorous fish from the Pacific Ocean, and saturated fatty acid levels were high in fish from the Indian Ocean. The results of this study will be of value in determining the dietary usefulness of fish caught in Sri Lanka. PMID- 27373422 TI - Synthesis and Monolayer Behaviors of Novel Hybrid Corynomycolic Acids Containing Semifluoroalkyl Groups. AB - In this work, novel hybrid-type corynomycolic acids [hybrid-OH and hybrid-COOH, with semifluoroalkyl groups (Rf-(CH2)n-: Rf = C4F9, n = 6 and Rf = C6F13, n = 3) located on the carbon atoms attached to the hydroxyl and carboxylic acid groups (C-OH and C-COOH), respectively] were successfully synthesized. The behaviors and formation of hybrid corynomycolic acid monolayers at the air-water interface were investigated by surface tension and surface pressure-area (pi-A) measurements to clarify the effects of the Rf chain length, position of the semifluoroalkyl group, and surfactant molecule stereochemistry. Compared to dialkyl corynomycolic acid, both the critical micelle concentration (CMC) and the surface tension at the CMC (gammaCMC) of hybrid corynomycolic acids were reduced by the presence of the Rf group. With respect to the surface tension versus log concentration (gamma vs. log C) isotherms, all syn-isomers of the hybrid-OH and hybrid-COOH acids showed two break points, while the anti-isomers showed only one break point. These different isotherms can be explained in terms of the steric repulsion between the two hydrophilic groups (OH and COO(-)), which depend on the stereochemistry of the surfactant. No effect of the location of the semifluoroalkyl group was observed. With respect to the formation of a monolayer film, four parameters-the lift-off area (AL), zero-pressure molecular area (A0), maximum of the Gibbs elastic modulus [EG (max)], and monolayer collapse pressure (pic)-were measured. Both AL and A0 of all hybrid corynomycolic acids were larger than the corresponding dialkyl acids due to the bulky and rigid Rf groups. Interestingly, syn- and anti-hybrids had almost identical isotherms on compression, although the values of pic of anti-hybrids were higher than those of syn-isomers. In addition, the values of EG (max) of hybrid-COOHs were slightly larger than those of the corresponding hybrid-OHs. Using the nascent soap method (agent-in-oil method), we found that anti-F4C6-OH (a hybrid corynomycolic acid) is a promising emulsifier for a ternary system comprising octane, water, and perfluoropolyether oil. PMID- 27373423 TI - Cynaropicrin is dual regulator for both degradation factors and synthesis factors in the cartilage metabolism. AB - AIMS: The molecular mechanism of osteoarthritis (OA) has never been understood clearly, but it has been suggested that imbalance of degradation and synthesis in cartilage contribute to the underlying mechanisms of OA. In this study, we investigated the effectiveness in the cartilage metabolism of the artichoke extract that includes the compound cynaropicrin. MAIN METHODS: We evaluated the efficacy of the artichoke extract or cynaropicrin in the cartilage metabolism factors and NF-kappaB signaling activity stimulated by inflammatory cytokine in chondrogenic cell lines, OUMS-27 and SW1353, using qRT-PCR, immunofluorescence and immunoblotting. KEY FINDINGS: We initially found that an artichoke extract and cynaropicrin both inhibited the increase of cartilage degradation factor MMP13 and further decreased the synthesis factor aggrecan induced by TNF-alpha in OUMS-27. In addition, cynaropicrin suppressed the enhancement of master regulator HIF-2alpha on cartilage degradation and further reduced the master regulator Sox9 on cartilage synthesis induced by TNF-alpha. We observed that cynaropicrin suppresses NF-kappaB signaling, which controls HIF-2alpha and Sox9. Since, HIF 2alpha is induced by p65 (RelA), we evaluated the effect of cynaropicrin and observed that it suppressed the nuclear transport of p65 (RelA) by inhibiting phosphorylation of IkappaBalpha. Moreover, cynaropicrin not only suppressed TNF alpha stimulation, it had a similar effect on IL-1beta stimulation. No significant cytotoxicity with cynaropicrin was observed. SIGNIFICANCE: These finding suggest that cynaropicrin is an effective substance that can improve the balance of cartilage metabolism, by altering the equilibrium of cartilage degradation and synthesis induced by multiple mediators know to contribute to OA. PMID- 27373424 TI - Estrogens do not protect, but androgens exacerbate, collagen accumulation in the female mouse kidney after ureteric obstruction. AB - AIMS: Controversy surrounds the gender basis of progression in chronic kidney disease. Unfortunately, most experimental studies addressing this question do not distinguish between direct effects of estrogen and indirect activation of estrogen receptors through conversion of testosterone to 17beta-estradiol by aromatase. We examined the pathogenesis of renal fibrosis in female aromatase knockout (ArKO) mice, which lack circulating and stored estrogens, while having normal levels of testosterone. MAIN METHODS: ArKO mice and their wild-type (ArWT) counterparts were subjected to unilateral ureteric obstruction (UUO), with kidney tissue collected at day(D) 0, 3 and 9 post-UUO. Effects of 5alpha dihydrotestosterone (DHT) administration on each genotype were also studied. Tissue was assessed biochemically and histochemically for fibrosis. Western blot analysis was used to measure alpha-smooth muscle actin (alpha-SMA) expression and TGF-beta1 signalling. Matrix metalloproteinase-2 (MMP-2) activity was measured by zymography. KEY FINDINGS: UUO increased collagen content over time (p<0.05 (D3) and p<0.01 (D9) vs day 0), with no difference between genotypes in qualitative (collagen IV staining) and quantitative (hydroxyproline concentration) analyses. Systemic administration of non-aromatizable DHT increased collagen content after 3days of UUO in both genotypes. This was not paralleled by any change in alpha SMA (myofibroblast burden) or TGF-beta1 signalling but was commensurate with DHT reducing MMP2 activity in both genotypes (p<0.05 vs genotype controls). SIGNIFICANCE: Physiological concentrations of estrogens do not protect the injured kidney from fibrosis progression. Androgens rather than estrogens are the relevant factor involved in regulating disease-related renal scarring in this model. PMID- 27373425 TI - The link between TLR7 signaling and hepatitis B virus infection. AB - Toll-Like Receptors (TLRs) play crucial roles in recognition and induction of appropriate immune responses against viral infections, including hepatitis B. TLR7 detects intracellular viral single strand RNA which leads to the activation of several pro-inflammatory transcription factors via the MYD88 dependent pathway. Patients with prolonged infectious forms of hepatitis B, including active and inactive chronic forms, are unable to clear HBV from hepatocytes completely. It is believed that the differences in genetic and immunological parameters of the patients and clearance subjects, who successfully clear HBV infections, are the main factors responsible for allowing the long term infections to persist. It appears that defective expression of TLR7 may result in impaired immune responses against HBV. The aim of this review is to address the recent information regarding the crucial roles played by TLR7 in hepatitis B infection and also the main mechanisms used by HBV to escape from recognition by TLR7 in prolonged HBV infected patients. Considering that chronic hepatitis B infection is not yet curable, it could be possible to activate TLR7-related immunological pathways as a therapy directed towards persistent HBV infection. Hence, another aim of this study is to present recent developments of TLR7 agonists as a therapeutic strategy for chronic hepatitis B. PMID- 27373426 TI - Structural characterization, catalytic, kinetic and thermodynamic properties of Aspergillus oryzae tannase. AB - Tannase (EC.3.1.1.20) from Aspergillus oryzae was purified using ammonium sulphate precipitation (75%), gel filtration chromatography through Sephadex G 100, and G-200. The purified enzyme was monomeric protein with a molecular mass of 106kDa. The activation energy for tannic acid hydrolysis was 32.6kJmol-1 and its temperature quotient (Q10) was 1.0. The pKa1 and pKa2 values of acidic and basic limbs of the active site residues were 4.6 and 6.4. The calculated values of thermodynamic parameters for tannic acid hydrolysis, were as follows: DeltaH*=30.02kJmol-1, DeltaG*=59.75kJmol-1 DeltaS*=-95.90Jmol-1K-1, (DeltaG*E S)=3.66kJmol-1 and DeltaG*E-T -12.61kJmol-1. The pure enzyme exhibited Km, Vmax and kcat of 4.13mM, 3507Umgprotein-1 and 551.4s-1. The calculated half-life time at 40, 45, 50, 55, 60, and 70 degrees C was 955.15, 142.0, 30.28, 17.88, 8.23 and 2.95min, respectively. The thermodynamic parameters for irreversible thermal inactivation at different temperatures (40-70 degrees C) were determined. The enzyme was activated by Ca2+, and Mg2+ while Hg2+, Fe2+, and Cu2+ strongly inhibited it. Hydrolysis of tannic acid by the pure enzyme indicated that gallic acid was the end-product. PMID- 27373427 TI - Galactoxyloglucan-doxorubicin nanoparticles exerts superior cytotoxic effects on cancer cells-A mechanistic and in silico approach. AB - Galactoxyloglucan (PST001), isolated from seed kernel of Tamarindus indica is a non-toxic immunostimlatory agent with selective cytotoxicity on cancer cells. Toxicity associated with the chemotherapeutic drug doxorubicin (Dox) is the major barrier in its clinical application. Stable, spherically shaped PST-Dox nanoparticles with an average size of 10nm were prepared via ionic gelation of Dox with PST001 which displayed a pH dependent cumulative Dox release kinetics. PST-Dox nanoparticles demonstrated cancer-specific enhanced cytotoxic effects than PST001 and Dox in cancer cells by enhanced cellular uptake of Dox through the induction of apoptosis, sparing normal cells and RBCs. Elucidation of molecular mechanism by whole genome microarray revealed down-regulation of tyrosine kinase oncogenic pathways as PST-Dox mode of action. An in silico model of PST-Dox was developed and computed the activity against topoisomerase IIbeta, human Abl kinase and protein tyrosine kinases. Computational studies further affirmed the findings of genomic and proteomic investigations with an increased interaction energy between PST-Dox complexes with target system than with Dox and PST001 alone. The important findings and profoundly restrained methodologies highlighted in the current study will accelerate the therapeutic potential of this nanoparticle formulation for substantial clinical studies and testing in several cancers. To conclude, PST-Dox nanoparticles represent a superior drug delivery nanosystem for the effective treatment of cancer even though detailed investigations are warranted. PMID- 27373428 TI - Physicochemical of microcrystalline cellulose from oil palm fronds as potential methylene blue adsorbents. AB - The present study sheds light on the physical and chemical characteristics of microcrystalline cellulose (MCC) isolated from oil palm fronds (OPF) pulps. It was found that the OPF MCC was identified as cellulose II polymorph, with higher crystallinity index than OPF alpha-cellulose (CrIOPFMCC: 71%>CrIOPFalpha cellulose: 47%). This indicates that the acid hydrolysis allows the production of cellulose that is highly crystalline. BET surface area of OPF MCC was found to be higher than OPF alpha-cellulose (SBETOPFMCC: 5.64m2g-1>SBETOPFalpha-cellulose:Qa0 2.04m2g-1), which corroborates their potential as an adsorbent. In batch adsorption studies, it was observed that the experimental data fit well with Langmuir adsorption isotherm in comparison to Freundlich isotherm. The monolayer adsorption capacity (Qa0) of OPF MCC was found to be around 51.811mgg-1 and the experimental data fitted well to pseudo-second-order kinetic model. PMID- 27373429 TI - Homogeneous synthesis of Ag nanoparticles-doped water-soluble cellulose acetate for versatile applications. AB - We report a facile and efficient approach for synthesis of well-dispersed and stable silver nanoparticles (Ag NPs) using water-soluble cellulose acetate (CA) as both reductant and stabilizer. Partially substituted CA with highly active hydroxyl groups and excellent water-solubility is able to reduce silver ions in homogeneous aqueous medium effectively. The synthesized Ag NPs were characterized by UV-vis spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy and energy dispersive X-ray spectroscope analysis. The as-prepared Ag NPs were well-dispersed, showing a surface plasmon resonance peak at 426nm. The resulted Ag NPs@CA nanohybrids exhibit high catalytic activity for the reduction of 4-nitrophenol to 4-aminophenol in the presence of NaBH4. Meanwhile, the nanohybrids are also effective in inhibiting the growth of bacterial. This environmentally friendly method promotes the use of renewable natural resources to prepare a variety of inorganic-organic materials for catalysis, antibacterial, sensors and other applications. PMID- 27373430 TI - Cryptosporidium species and Cryptosporidium parvum subtypes in dairy calves and goat kids reared under traditional farming systems in Turkey. AB - Molecular characterizations of Cryptosporidium spp. in ruminants reared under traditional animal management systems are scarce and studies conducted thus far have revealed largely an absence of the pathogenic and zoonotic species Cryptosporidium parvum in pre-weaned animals. In this study, we examined Cryptosporidium species and subtype distribution in free-range pre-weaned dairy calves and goat kids with diarrhea. Cryptosporidium-positive specimens from pre weaned calves on 10 farms and goat kids on 4 farms in Ankara, Balikesir, Corum, Kirikkale, and Kirsehir Provinces, Turkey were genotyped by PCR-restriction length polymorphism analysis of the small subunit rRNA gene, which identified C. parvum in 27 calves and 9 goat kids and Cryptosporidium ryanae in 1 calf. Among the C. parvum isolates successfully subtyped by DNA sequence analysis of the 60 kDa glycoprotein gene, three subtypes were detected in calves, including IIaA13G2R1 (20/23), IIdA18G1 (2/23), and IIdA20G1b (1/23), and four subtypes were detected in goat kids, including IIaA13G2R1 (3/8), IIaA15G1R1 (2/8), IIdA22G1 (2/8), and IIdA18G1 (1/8). Data of the study suggest that dairy calves reared in a traditional cow-calf system in Turkey are mainly infected with a C. parvum subtype rarely seen elsewhere, whereas goat kids are infected with diverse subtypes. As all five C. parvum subtypes found in this study are known human pathogens, pre-weaned farm animals could play a potential role in the transmission of human cryptosporidiosis. PMID- 27373431 TI - In vivo and in vitro effects of the herbicide Roundup((r)) on developmental stages of the trematode Echinostoma paraensei. AB - The exposure of wildlife and humans to toxic residues of Roundup((r)) through agricultural practices or the food chain has been reported since the herbicide was found contaminating rivers. Glyphosate, N-(phosphonomethyl)glycine acid, is a nonselective post-emergent herbicide and is formulated as an isopropylamine salt with the surfactant taloamine polyethoxylate (POEA) representing the commercial formulation of Roundup((r)). There is little knowledge about the effects of the herbicide on helminth parasites, particularly those whose life cycle is related to water bodies. Here we investigated the effects of the Roundup((r)) on the food borne trematode Echinostoma paraensei in experimental conditions using different developmental stages (eggs, miracidia, cercariae, metacercariae, newly excysted larvae (NEL), helminths at seven days and helminths at fourteen days). Three different herbicide concentrations were tested based on concentrations typically applied in the field: 225, 450 and 900 mg/L. Specimens were analyzed in vitro for hatching miracidia, mortality and excystment rate of metacercariae and in vivo for parasitic load and egg production. There was a significant difference in the hatching miracidia rate only for the newly embryonated eggs. The mortality of specimens and excystment rate of metacercariae were concentration-dependent. There was a significant difference in the miracidia mortality with respect to concentration until 56.3 mg/L. The same effect was observed for cercariae, and mortality was observed from 15 min onwards at concentrations of 225-900 mg/L. At low concentrations, mortality was detected after 30 min. The effects of the herbicide concentration on NEL and on helminths at seven and fourteen days showed a significant difference after 24 h. There was no significant difference in parasitic load and egg production after infection of rodents with exposed metacercariae. All developmental stages of the trematode E. paraensei were affected by Roundup((r)) exposure under experimental conditions. These results suggest that dynamics of transmission of the trematode could be affected in the natural environments. The study also reinforces the usefulness of this trematode as a good model organism to test pesticides regarding human and environmental health. PMID- 27373432 TI - A Plasmodium falciparum S33 proline aminopeptidase is associated with changes in erythrocyte deformability. AB - Infection with the apicomplexan parasite Plasmodium falciparum is a major cause of morbidity and mortality worldwide. One of the striking features of this parasite is its ability to remodel and decrease the deformability of host red blood cells, a process that contributes to disease. To further understand the virulence of Pf we investigated the biochemistry and function of a putative Pf S33 proline aminopeptidase (PfPAP). Unlike other P. falciparum aminopeptidases, PfPAP contains a predicted protein export element that is non-syntenic with other human infecting Plasmodium species. Characterization of PfPAP demonstrated that it is exported into the host red blood cell and that it is a prolyl aminopeptidase with a preference for N-terminal proline substrates. In addition genetic deletion of this exopeptidase was shown to lead to an increase in the deformability of parasite-infected red cells and in reduced adherence to the endothelial cell receptor CD36 under flow conditions. Our studies suggest that PfPAP plays a role in the rigidification and adhesion of infected red blood cells to endothelial surface receptors, a role that may make this protein a novel target for anti-disease interventions strategies. PMID- 27373433 TI - Treatment of Hypoglycemia in Adult Patients with Type 1 Diabetes: An Observational Study. AB - OBJECTIVES: 1) To characterize the nutritional treatment of hypoglycemia in adult patients with type 1 diabetes mellitus and 2) to compare the characteristics of participants who follow the recommendations with the characteristics of those who do not. METHODS: A total of 121 adults with type 1 diabetes were included in this cross-sectional analysis. Participants completed a food record and a glycemia and insulin doses logbook to collect data on mild to moderate hypoglycemic events (glycemia <4.0 mmol/L or 4.0 to 5.0 mmol/L with symptoms) and their treatments over a 2-day period. Participants were identified as overcorrecting if they consumed, within 15 minutes after the episode, >20g of carbohydrates for correction. Self-administered questionnaires about fear of hypoglycemia were completed, and cardiometabolic profile variables were measured (glycated hemoglobin, blood pressure, lipid profile and body mass indexes). RESULTS: Of the 121 participants, 94 (78%) reported at least 1 hypoglycemic event, for a total of 271 events (2.2+/-2.1 episodes per patient). Of these events, 64% were treated within 15 minutes, and they were treated primarily with fruit juice or sweet beverages (39%) or mixed snacks (29%). Average carbohydrate intake for treatment was 32+/-24 grams. Of the participants, 73% overtreated their episodes. They were significantly younger and had greater fear of hypoglycemia than those who treated the episodes adequately. No difference was observed for cardiometabolic variables. CONCLUSIONS: The majority of patients in our cohort overtreated their hypoglycemic episodes. These results suggest that hypoglycemia-correction education needs to be reinforced. PMID- 27373434 TI - Factors Affecting Number of Diabetes Management Activities Provided by Pharmacists. AB - BACKGROUND: Legislative changes since 2007 have given Alberta pharmacists additional authorizations and new practice settings, which should enhance provision of clinical services to patients. This study examined whether these changes are related to the number of diabetes management activities provided by pharmacists. METHODS: Cross-sectional surveys of Alberta pharmacists were conducted in 2006 and 2015. Both questionnaires contained 63 diabetes management activities, with response options to indicate how frequently the activity was provided. Respondents were grouped by survey year, practice setting, diabetes specific training and additional authorizations. The number of diabetes management activities provided often or always were compared among groups by using analysis of variance. RESULTS: Data from 128 pharmacists participating in the 2006 survey were compared with 256 pharmacists participating in the 2015 survey; overall mean age was 41.6 (+/-10.9) years, 245 (64%) were women, mean duration of practice was 16.1 (+/-11.8) years, 280 (73%) were community pharmacists, 75 (20%) were certified diabetes educators (CDEs), and 100 (26%) had additional prescribing authorization (APA). Pharmacists provided a mean of 28.7 (95% CI 26.3 to 31.2) diabetes management activities in 2006 and 35.2 (95% CI 33.4-37.0) activities in 2015 (p<0.001). Pharmacists who were CDEs provided significantly more activities compared to other pharmacists (p<0.001). In 2015, working in a primary care network and having APA were also associated with provision of more activities (p<0.05 for both comparisons). CONCLUSIONS: Pharmacists provided more diabetes management activities in 2015 than in 2006. The number of diabetes management activities was also associated with being a CDE, working in a primary care network or having APA. PMID- 27373436 TI - Can a short internet training program improve social isolation and self-esteem in older adults with psychiatric conditions? AB - The purpose of this study was to investigate whether an educational training course on using the internet and touchscreen technology (TT) would decrease social isolation and improve self-esteem in residents living in a low-level residential facility. Twelve sessions over six weeks with two facilitators were provided to five participants with a variety of psychiatric disorders. Measures were completed before and after the 12 sessions. There were no statistically significant improvements or worsening in social isolation (mean score 6.2, SD 3.35) or self-esteem (mean score 18.2, SD 3.56) post the training sessions for the residents. Qualitative feedback suggested that the residents enjoyed this experience and learnt new skills. Further study is recommended using larger samples and alternative outcomes measures. PMID- 27373435 TI - Effects of S-Allylcysteine on Biomarkers of the Polyol Pathway in Rats with Type 2 Diabetes. AB - OBJECTIVES: We evaluated the effects of S-allylcysteine (SAC) on biomarkers of the polyol pathway in streptozotocin-nicotinamide (STZ-NA)-induced diabetes in rats. METHODS: Diabetes was induced in male albino Wistar rats by intraperitoneal administration of STZ (55 mg kg-1 bw-1) and NA (110 mg kg-1 bw-1). SAC (150 mg kg 1 bw-1) was orally administered to the rats with diabetes for 45 days to assess its effects on blood glucose, insulin, insulin resistance, glycated hemoglobin, aldose reductase (AR), sorbitol dehydrogenase (SDH), sorbitol, fructose, thiobarbituric acid-reactive substances (TBARS), hydroperoxide, hemoglobin and glutathione (GSH). RESULTS: On SAC administration in the rats with diabetes, the levels of blood glucose, insulin resistance, glycated hemoglobin, AR, SDH, sorbitol, fructose, TBARS and hydroperoxide increased significantly (p<0.05), whereas those of insulin, hemoglobin and GSH decreased. SAC showed therapeutic effects similar to those of gliclazide in decreasing blood glucose, AR, SDH, sorbitol, fructose, glycosylated hemoglobin, TBARS and hydroperoxides levels and significant increases in insulin, hemoglobin and GSH activity in rats with diabetes. Moreover, histopathologic studies also revealed the protective effect of SAC on pancreatic beta cells. CONCLUSIONS: The results indicate that SAC prevents complications of diabetes by reducing the influx of glucose in the polyol pathway, thereby elevating the GSH level and reducing the activities of AR and SDH. Therefore, SAC may have imperative implications for the deterrence and early treatment of type 2 diabetes. PMID- 27373437 TI - Redox-responsive star-shaped magnetic micelles with active-targeted and magnetic guided functions for cancer therapy. AB - Highly efficient delivery of therapeutic agents to target sites is of great importance for achieving excellent therapeutic efficacy in cancer treatment. Here, we report a redox-responsive star-shaped magnetic micelle with both active targeted and magnetic-guided functions. The magnetic star-shaped micelles are formed by self-assembly of four-arm poly(ethylene glycol) (PEG)-poly(epsilon caprolactone) (PCL) copolymers with disulfide bonds as intermediate linkers. Anticancer drug doxorubicin (DOX) and magnetic iron oxide nanoparticles (Fe3O4) are simultaneously encapsulated into the hydrophobic cores. PBA ligands are chemically conjugated to the end of the hydrophilic PEG segments, endowing the active targeting of nanocarriers. Both qualitative and quantitative analyses of the intracellular uptake of these micelles with active-targeting and dual targeting are performed in vitro by cultured with salic acid (SA)-positive tumor cells (human liver carcinoma cell line HepG2, human cervical cancer cell line HeLa) and SA-negative tumor cells (human breast adenocarcinoma cell line MCF-7, human non-small cell lung cancer cell line A549) in the presence or absence of a permanent magnetic field. In vivo biodistribution studies with active-targeting and dual-targeting and in vivo anti-tumor effect are carried out in detail after being applied to the BALB/c mice bearing mouse H22 hepatocarcinoma cells tumor model. These in vivo results demonstrate that a great amount of dual-targeted magnetic micelles accumulate around the tumor tissues by the magnetic-guiding and in turn are taken up by the tumor cells through SA-mediated endocytosis, leading to a high therapeutic efficacy to the artificial solid tumor. STATEMENT OF SIGNIFICANCE: A redox-responsive star-shaped magnetic micelle with both active targeted and magnetic-guided functions was developed. Both qualitative and quantitative analysis of the intracellular uptake with dual-targeting of these micelles were performed in vitro by salic acid (SA)-positive tumor cells. The in vivo results demonstrate that a great amount of dual-targeted magnetic micelles accumulated around the tumor tissues, leading to a high therapeutic efficacy to artificial solid tumor. PMID- 27373438 TI - A novel inhaled phosphodiesterase 4 inhibitor (CHF6001) reduces the allergen challenge response in asthmatic patients. AB - CHF6001 is an inhaled phosphodiesterase 4 (PDE4) inhibitor in development for the treatment of obstructive lung diseases. The efficacy and safety of CHF6001 were investigated in a double blind, placebo controlled, 3-way cross-over study using the allergen challenge model. Thirty-six atopic asthmatics who were not taking inhaled corticosteroids and who demonstrated a late asthmatic response (LAR) to inhaled allergen at screening were randomised to receive CHF6001 400 MUg or 1200 MUg or placebo administered once a day using a dry powder inhaler. The three treatment periods were 9 days; allergen challenges were performed on day 9 and induced sputum was obtained after 10 h from challenge. Washout periods between treatments were up to 5 weeks. Both CHF6001 doses significantly attenuated the LAR; the primary endpoint analysis showed that CHF6001 400 MUg and 1200 MUg caused reductions of 19.7% (p = 0.015) and 28.2% (p < 0.001) respectively of the weighted FEV1 AUC4-10h compared with placebo. The difference between the CHF6001 doses was not statistically significant (p = 0.223). Compared with placebo, CHF6001 caused greater reduction in sputum eosinophil counts, although these changes were not statistically significant. CHF6001 was well tolerated, with similar numbers of adverse events in each treatment period. This inhaled PDE4 inhibitor has the potential to provide clinical benefits in patients with atopic asthma. PMID- 27373439 TI - Impact of statins on ALI/ARDS: A meta-analysis. AB - BACKGROUND: Statins may be beneficial in treating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), but their application remains controversial. OBJECTIVES: This meta-analysis of published studies investigated their potential benefit in ALI/ARDS treatment. METHODS: PubMed, EMBASE, Google Scholar and Cochrane databases were searched and all randomized controlled trials (RCT) and cohort studies with head-to-head comparison between statin and standard care were included. RESULTS: Three RCTs and six cohort studies were included. Overall, statins treatment had no significant effect on mortality compared with placebo (RCTs: OR = 0.99, 95% CI = 0.72, 1.37; cohorts: OR = 0.99, 95% CI = 0.71, 1.37). In addition, ventilator-free days were comparable between the two groups (RCTs: SMD = 0.08, 95% CI = -0.03, 0.19; cohorts: SMD = 0.06, 95% CI = -0.17, 0.29). The one-way sensitivity analysis confirmed the stability of results. CONCLUSION: The results did not show that statins had effects on mortality and ventilator-free days among ALI/ARDS patients. However, this meta-analysis is limited by the number of RCTs included. PMID- 27373440 TI - Low reversibility of intracellular cAMP accumulation in mouse Leydig tumor cells (MLTC-1) stimulated by human Luteinizing Hormone (hLH) and Chorionic Gonadotropin (hCG). AB - In order to study the intracellular cAMP response kinetics of Leydig cells to hormones with LH activity, we used MLTC-1 cells transiently expressing a chimeric cAMP-responsive luciferase so that real-time variations of intracellular cAMP concentration could be followed using oxiluciferin luminescence produced from catalyzed luciferin oxidation. The potencies of the different LHs and CGs were evaluated using areas under the curves (AUC) of their kinetics over 60 min stimulation. All mammalian LHs and CGs tested were found to stimulate cAMP accumulation in these cells. The reversibility of this stimulation was studied by removing the hormone from the culture medium after 10 min of incubation. The ratios of kinetics AUC after removing or not the hormone were used to evaluate the stimulation reversibility of each hormone. Natural and recombinant hLHs and hCGs were found to exhibit slowly reversible activation compared to pituitary rat, ovine, porcine, camel and equine LHs, serum-derived eCG (PMSG) and recombinant eLH/CGs. Carbohydrate side chains are not involved in this phenomenon since natural and recombinant homologous hormones exhibit the same reversibility rates. It is still unknown whether only one human subunit, alpha or beta, is responsible for this behaviour or whether it is due to a particular feature of the hLH and hCG quaternary structure. PMID- 27373441 TI - Coats-like retinopathy in Joubert syndrome. AB - An 11-year-old girl with Joubert syndrome was evaluated for a dim red reflex in her left eye. Fundus examination revealed retinal telangiectasias bilaterally compatible with Coats-like pigmentary retinopathy, a phenomenon not previously reported in Joubert syndrome. Coats-like exudative retinopathy may result in permanent visual loss if left untreated. The exudative retinopathy was controlled after multiple sessions of indirect laser photocoagulation and cryotherapy, with a good visual outcome. PMID- 27373442 TI - Dental Age Estimation: A Test of the Reliability of Correctly Identifying a Subject Over 18 Years of Age Using the Gold Standard of Chronological Age as the Comparator. AB - This study was designed to test the reliability of using the third molars to demarcate between child and adult status. A total of 2000 dental panoramic tomographs were used for assessment of the calculated age using the 8-stage system of tooth development and applied to all four third molars. The LL8 was also assessed using this 8-stage system. For each tooth development stage, the Normal distribution and percentile summary data were estimated. The calculated dental age compared with the chronological age was statistically significantly different (p < 0.001) for both females and males giving underestimates of the true age. Comparison of single tooth dental age and chronological age was only slightly different. The most important finding is that the assignment to above or below the 18-year threshold, in the age range 17 years to 19 years, could be wrong on up to 50% of occasions. PMID- 27373445 TI - Corrigendum. PMID- 27373444 TI - The ENT boot camp: an effective training method for ENT induction. PMID- 27373446 TI - Does leaf shedding protect stems from cavitation during seasonal droughts? A test of the hydraulic fuse hypothesis. AB - During droughts, leaves are predicted to act as 'hydraulic fuses' by shedding when plants reach critically low water potential (Psiplant ), thereby slowing water loss, stabilizing Psiplant and protecting against cavitation-induced loss of stem hydraulic conductivity (Ks ). We tested these predictions among trees in seasonally dry tropical forests, where leaf shedding is common, yet variable, among species. We tracked leaf phenology, Psiplant and Ks in saplings of six tree species distributed across two forests. Species differed in their timing and extent of leaf shedding, yet converged in shedding leaves as they approached the Psiplant value associated with a 50% loss of Ks and at which their model estimated maximum sustainable transpiration rate approached zero. However, after shedding all leaves, the Psiplant value of one species, Genipa americana, continued to decline, indicating that water loss continued after leaf shedding. Ks was highly variable among saplings within species and seasons, suggesting a minimal influence of seasonal drought on Ks . Hydraulic limits appear to drive diverse patterns of leaf shedding among tropical trees, supporting the hydraulic fuse hypothesis. However, leaf shedding is not universally effective at stabilizing Psiplant , suggesting that the main function of drought deciduousness may vary among species. PMID- 27373447 TI - Comment on Roughan et al.: Meloxicam prevents COX-2-mediated post-surgical inflammation but not pain following laparotomy in mice. PMID- 27373448 TI - Authors' reply to the comment by Ruan. PMID- 27373449 TI - Convergence and divergence in a long-term old-field succession: the importance of spatial scale and species abundance. AB - Whether plant communities in a given region converge towards a particular stable state during succession has long been debated, but rarely tested at a sufficiently long time scale. By analysing a 50-year continuous study of post agricultural secondary succession in New Jersey, USA, we show that the extent of community convergence varies with the spatial scale and species abundance classes. At the larger field scale, abundance-based dissimilarities among communities decreased over time, indicating convergence of dominant species, whereas incidence-based dissimilarities showed little temporal tend, indicating no sign of convergence. In contrast, plots within each field diverged in both species composition and abundance. Abundance-based successional rates decreased over time, whereas rare species and herbaceous plants showed little change in temporal turnover rates. Initial abandonment conditions only influenced community structure early in succession. Overall, our findings provide strong evidence for scale and abundance dependence of stochastic and deterministic processes over old field succession. PMID- 27373450 TI - Effect of Potassium Bromate on the Liver of Adult Male Albino Rat and A Possible Protective Role of Vitamin C: Histological, Immunohistochemical, and Biochemical Study. AB - Potassium bromate (KBrO3 ) is a food additive which is used primarily as a maturing agent for flour. It is proved as a toxic agent with significant reduction in the activities of antioxidant capacity. The therapeutic efficacy of vitamin C as antioxidant may provide a possible solution to KBrO3 mediated oxidative damage. Twenty four adult male albino rats were used to evaluate the protective role of vitamin C against KBrO3 induced hepatotoxicity and divided into four groups; Group 1 (control), Group 2: received 30 mg/Kg/day vitamin C orally for 4 weeks, Group 3: received 20 mg/Kg/dose KBrO3 orally twice weekly for 4 weeks and Group 4: received both KBrO3 and vitamin C. Liver specimens were processed for histological study by light and electron microscopes and stained immunohistochemically to detect glial fibriller acidic protein (GFAP). Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were estimated as well as the levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities in all dissected tissues were determined. KBrO3 induced histological alterations in the form of degeneration, cellular infiltration and significant increase in collagen deposition in portal tracts with a significant increase in immunoexpression of GFAP. Significant rise in serum levels of AST, ALT, and MDA in liver tissues were recorded. However, levels of GSH and SOD were significantly decreased. Most of these changes were improved by vitamin C treatment. In conclusion, vitamin C ameliorates the histological and biochemical alterations of the liver induced by KBrO3 . Anat Rec, 299:1256-1269, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27373451 TI - Peracetic Acid Depolymerization of Biorefinery Lignin for Production of Selective Monomeric Phenolic Compounds. AB - Lignin is the largest source of renewable material with an aromatic skeleton. However, due to the recalcitrant and heterogeneous nature of the lignin polymer, it has been a challenge to effectively depolymerize lignin and produce high-value chemicals with high selectivity. In this study, a highly efficient lignin-to monomeric phenolic compounds (MPC) conversion method based on peracetic acid (PAA) treatment was reported. PAA treatment of two biorefinery lignin samples, diluted acid pretreated corn stover lignin (DACSL) and steam exploded spruce lignin (SESPL), led to complete solubilization and production of selective hydroxylated monomeric phenolic compounds (MPC-H) and monomeric phenolic acid compounds (MPC-A) including 4-hydroxy-2-methoxyphenol, p-hydroxybenzoic acid, vanillic acid, syringic acid, and 3,4-dihydroxybenzoic acid. The maximized MPC yields obtained were 18 and 22 % based on the initial weight of the lignin in SESPL and DACSL, respectively. However, we found that the addition of niobium pentoxide catalyst to PAA treatment of lignin can significantly improve the MPC yields up to 47 %. The key reaction steps and main mechanisms involved in this new lignin-to-MPC valorization pathway were investigated and elucidated. PMID- 27373452 TI - Transvenous stimulation of the phrenic nerve for the treatment of central sleep apnoea: 12 months' experience with the remede(r) System. AB - AIMS: Patients with central sleep apnoea (CSA) often have poor quality of life and are at increased risk of morbidity and mortality. This study sought to evaluate the 12-month clinical outcomes of patients with CSA treated with unilateral transvenous phrenic nerve stimulation in the prospective, multicentre, non-randomized remede(r) System pilot study. METHODS AND RESULTS: Forty-seven patients with CSA were treated with the remede(r) System (Respicardia Inc., Minnetonka, MN, USA) for a minimum of 3 months. Sleep-disordered breathing parameters were evaluated by polysomnography (PSG) at 3, 6, and 12-month follow up. Sleep symptoms and quality of life were also evaluated. Forty-one patients completed all follow-up PSGs and were included in the analysis. At 12 months, there was sustained improvement compared with baseline in the apnoea-hypopnoea index (49.9 +/- 15.1 vs. 27.5 +/- 18.3 events/h, P < 0.001) and central apnoea index (28.2 +/- 15.0 vs. 6.0 +/- 9.2 events/h, P < 0.001). Sustained improvement in the oxygen desaturation index (46.1 +/- 19.1 vs. 26.9 +/- 18.0 events/h, P < 0.001), rapid eye movement sleep (11.4 +/- 6.1% vs. 17.1 +/- 8.0%, P < 0.001), and sleep efficiency (69.3 +/- 16.9% vs. 75.6 +/- 17.1%, P = 0.024) were also observed. There were also continued favourable effects on sleepiness and quality of life. Three deaths unrelated to remede(r) System therapy and five serious adverse events occurred over 12 months of follow-up. CONCLUSION: The present study demonstrates that in patients with CSA, unilateral transvenous phrenic nerve stimulation is associated with sustained improvement in key sleep parameters, sleep symptoms, and quality of life over 12 months of follow-up. PMID- 27373453 TI - Voriconazole exposure regulates distinct cell-cycle and terminal differentiation pathways in primary human keratinocytes. PMID- 27373454 TI - Predictors of psychological outcomes in a longitudinal study of Latina breast cancer survivors. AB - OBJECTIVE: This study sought to investigate the unique contributions of socio ecological, cultural and cancer treatment-related factors in predicting depressive symptoms and cancer-specific distress among Latinas. DESIGN: Participants were 140 English or Spanish-speaking Latinas (Mage = 50.6) with non metastatic breast cancer who were assessed within two years of diagnosis (Time 1) and three months later (Time 2). MAIN MEASURES: Hierarchical regression analyses identified predictors of depressive symptoms and cancer-specific distress at Time 1 and 2. RESULTS: Most women scored above the clinical cut-offs for depressive symptoms and cancer-specific distress. After adjusting for socio-ecological factors, greater Latino enculturation, measured by Latino ethnic identity, was significantly associated with greater cancer-specific distress at Time 1 (beta = .20, p < .05). A significant interaction (p < .01) revealed that among women high on Latino identity, lower English language use was associated with more cancer specific distress than higher English language use. After adjusting for socio ecological factors, greater satisfaction with surgical treatment predicted improved depressive symptoms and cancer-specific distress across time (betas range from -.31 to -.18, ps < .01). CONCLUSIONS: Findings elucidate the complex relationship between culture and psychological outcomes in the breast cancer context and suggest that treatment satisfaction might be an important intervention target for Latinas. PMID- 27373455 TI - The detection of hydrogen peroxide involved in plant virus infection by fluorescence spectroscopy. AB - The production of reactive oxygen species (ROS) forms part of the defense reaction of plants against invading pathogens. ROS have multifaceted signaling functions in mediating the establishment of multiple responses. To verify whether hydrogen peroxide (H2 O2 ) contributes to plant virus infection and the development of induced symptoms, we used fluorescence to monitor the generation of H2 O2 and confocal laser scanning microscopy (CLSM) to investigate the subcellular distribution of H2 O2 in leaves. In this study, the M strain of Cucumber mosaic virus (M-CMV) induced heavy chlorotic symptoms in Nicotiana tabacum cv. white burley during systemic infection. Compared with mock-inoculated leaves, H2 O2 accumulation in inoculated leaves increased after inoculation, then decreased after 4 days. For systemically infected leaves that showed chlorotic symptoms, H2 O2 accumulation was always higher than in healthy leaves. Subcellular H2 O2 localization observed using CLSM showed that H2 O2 in inoculated leaves was generated mainly in the chloroplasts and cell wall, whereas in systemically infected leaves H2 O2 was generated mainly in the cytosol. The levels of coat protein in inoculated and systemically infected leaves might be associated with changes in the level of H2 O2 and symptom development. Further research is needed to elucidate the generation mechanism and the relationship between coat protein and oxidative stress during infection and symptom development. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27373456 TI - Bilateral polyorchidism with ipsilateral two undescended testes: a rare congenital anomaly. AB - Polyorchidism is defined as the presence of more than two testes. This rare congenital anomaly has been reported with only 140 pathologically proven cases in the published literature to date. While triorchidism is the most common variation and generally affects the left side, bilateral polyorchidism is even rare and only seven cases of patients with four testes have been reported in the literature. There is no consensus in the literature regarding the management of supernumerary testis due to its rareness. We report such a rare case of a 20-year old male patient, who was presented with left-sided scrotal mass and right inguinal swelling and, diagnosed as polyorchidism including four distinct testes, with two of them in left hemiscrotum and the other two testes in the right inguinal canal. The patient underwent orchiopexy for the normal looking right sided testis, and orchiectomy for the right-sided supernumerary testis being dysmorphic and potential malignancy risk. Histopathological examination confirmed the excised tissue to be severely atrophic testicle. The patient is still following with regular self-examination and scrotal ultrasonography. Polyorchidism should be keep in mind especially for the differential diagnosis of extratesticular and paratesticular masses. Physical examination may not be sufficient, and radiologic examination can provide accurate diagnosis. Conservative, extirpative or reconstructive approaches could be performed based on individual basis by reproductive potential and location of supernumerary testis, coexistence of other disorders and suspicion of malignancy. PMID- 27373457 TI - TEMPO Monolayers on Si(100) Electrodes: Electrostatic Effects by the Electrolyte and Semiconductor Space-Charge on the Electroactivity of a Persistent Radical. AB - This work demonstrates the effect of electrostatic interactions on the electroactivity of a persistent organic free radical. This was achieved by chemisorption of molecules of 4-azido-2,2,6,6-tetramethyl-1-piperdinyloxy (4 azido-TEMPO) onto monolayer-modified Si(100) electrodes using a two-step chemical procedure to preserve the open-shell state and hence the electroactivity of the nitroxide radical. Kinetic and thermodynamic parameters for the surface electrochemical reaction are investigated experimentally and analyzed with the aid of electrochemical digital simulations and quantum-chemical calculations of a theoretical model of the tethered TEMPO system. Interactions between the electrolyte anions and the TEMPO grafted on highly doped, i.e., metallic, electrodes can be tuned to predictably manipulate the oxidizing power of surface nitroxide/oxoammonium redox couple, hence showing the practical importance of the electrostatics on the electrolyte side of the radical monolayer. Conversely, for monolayers prepared on the poorly doped electrodes, the electrostatic interactions between the tethered TEMPO units and the semiconductor-side, i.e., space-charge, become dominant and result in drastic kinetic changes to the electroactivity of the radical monolayer as well as electrochemical nonidealities that can be explained as an increase in the self-interaction "a" parameter that leads to the Frumkin isotherm. PMID- 27373459 TI - Cout et Succes Du Traitement De L'Insuffisance Renale Terminale En Belgique: D'Ou Venons-Nous Et Ou Allons-Nous ? PMID- 27373458 TI - High-speed atomic force microscopy reveals strongly polarized movement of clostridial collagenase along collagen fibrils. AB - Bacterial collagenases involved in donor infection are widely applied in many fields due to their high activity and specificity; however, little is known regarding the mechanisms by which bacterial collagenases degrade insoluble collagen in host tissues. Using high-speed atomic force microscopy, we simultaneously visualized the hierarchical structure of collagen fibrils and the movement of a representative bacterial collagenase, Clostridium histolyticum type I collagenase (ColG), to determine the relationship between collagen structure and collagenase movement. Notably, ColG moved ~14.5 nm toward the collagen N terminus in ~3.8 s in a manner dependent on a catalytic zinc ion. While ColG was engaged, collagen molecules were not only degraded but also occasionally rearranged to thicken neighboring collagen fibrils. Importantly, we found a similarity of relationship between the enzyme-substrate interface structure and enzyme migration in collagen-collagenase and DNA-nuclease systems, which share a helical substrate structure, suggesting a common strategy in enzyme evolution. PMID- 27373460 TI - Quantification of Monoclonal Immunoglobulins by Immunochemical and Densitometry Techniques. AB - In comparing four currently available immunochemical methods for immunoglobulin quantification, i.e. radial immunodiffusion (RID), rate nephelometry (RN), laser nephelometry (LN) and turbidimetry (T), highly divergent results were obtained for monoclonal immunoglobulins. Comparison with data obtained by densitometric scanning (D) of the serum protein electrophoresis on cellulose acetate showed that these immunochemical techniques cannot be recommended for the quantification of monoclonal immunoglobulins, they may however remain useful for assessing relative changes in concentration during treatment. PMID- 27373461 TI - Septicaemia And Endocarditis Due to Streptococci of Lancefield Group. AB - Though beta haemolytic streptococci of Lancefield group B are important in the infectious pathology of the newborn, they are much less common in the adult and for this reason less well-known. In connection with a case of endocarditis due to streptococci of group B in an adult, we have reviewed the relatively scanty literature on the subject which describes only 38 cases. After defining the populations at special risk and indicating the reservoirs of groupe B streptococci in man, we report a number of uncommon features associated with endocarditis due to this organism and finish by discussine the theraphy. PMID- 27373462 TI - Medicaments Recemment Enregistres. PMID- 27373463 TI - Extraction and Purification of DNA from Complex Biological Sample Matrices Using Solid-Phase Microextraction Coupled with Real-Time PCR. AB - The determination of extremely small quantities of DNA from complex biological sample matrices represents a significant bottleneck in nucleic acid analysis. In this study, polymeric ionic liquid (PIL)-based solid-phase microextraction (SPME) was applied for the extraction and purification of DNA from crude bacterial cell lysate with subsequent quantification by real-time PCR (qPCR) analysis. Using an on-fiber ultraviolet initiated polymerization technique, eight different PIL sorbent coatings were generated and their DNA extraction performance evaluated using qPCR. The PIL sorbent coating featuring halide anions and carboxylic acid groups in the cationic portion exhibited superior DNA extraction capabilities when compared to the other studied PILs and a commercial polyacrylate SPME fiber. Electrostatic interactions as well as an ion-exchange mechanism were identified as the driving forces in DNA extraction by the PIL sorbents. The selectivity of the PIL sorbent coating for DNA was demonstrated in the presence of PCR inhibitors at high concentration, where a quantifiable amount of template DNA was extracted from aqueous samples containing CaCl2 and FeCl3. Furthermore, the PIL based SPME method was successfully applied for the extraction of DNA from crude bacterial cell lysate spiked with 1 pg mL(-1) template DNA without requiring the use of organic solvents or centrifugation steps. Following PIL-based SPME of DNA from a dilute cell lysate, the qPCR amplification efficiency was determined to be 100.3%, demonstrating the feasibility of the developed method to extract high purity DNA from complex sample matrices. PMID- 27373464 TI - Exploring Ag(111) Substrate for Epitaxially Growing Monolayer Stanene: A First Principles Study. AB - Stanene, a two-dimensional topological insulator composed of Sn atoms in a hexagonal lattice, is a promising contender to Si in nanoelectronics. Currently it is still a significant challenge to achieve large-area, high-quality monolayer stanene. We explore the potential of Ag(111) surface as an ideal substrate for the epitaxial growth of monolayer stanene. Using first-principles calculations, we study the stability of the structure of stanene in different epitaxial relations with respect to Ag(111) surface, and also the diffusion behavior of Sn adatom on Ag(111) surface. Our study reveals that: (1) the hexagonal structure of stanene monolayer is well reserved on Ag(111) surface; (2) the height of epitaxial stanene monolayer is comparable to the step height of the substrate, enabling the growth to cross the surface step and achieve a large-area stanene; (3) the perfect lattice structure of free-standing stanene can be achieved once the epitaxial stanene monolayer is detached from Ag(111) surface; and finally (4) the diffusion barrier of Sn adatom on Ag(111) surface is found to be only 0.041 eV, allowing the epitaxial growth of stanene monolayer even at low temperatures. Our above revelations strongly suggest that Ag(111) surface is an ideal candidate for growing large-area, high-quality monolayer stanene. PMID- 27373465 TI - Influence of the ultrasound pretreatment on anaerobic digestion of cattle manure, food waste and crude glycerine. AB - To increase the production of methane, when cattle manure (CM) is digested, pretreatments can be applied and/or the manure can be co-digested with other wastes. In this research work, a mixture of CM, food waste (FW) and raw glycerine (Gly) in a proportion in weight of 87% CM, 10% FW and 3% Gly was digested, (a) without pretreatment and (b) with pretreatment by ultrasound, applying a sonication energy of 1040 kJ/kg total solids. Specific methane production was 290 L CH4/kg volatile solids (VS) without pretreatment and 520 L CH4/kg VS with pretreatment. With respect to the volumetric methane production, 1.07 L CH4/Lreactor.day was produced in the first case, and in the second case, 1.98 L CH4/Lreactor.day. We can conclude that the application of ultrasound pretreatment significantly improved the production of biogas. PMID- 27373466 TI - Probing the spontaneous reduction mechanism of platinum ions confined in the nanospace by X-ray absorption fine structure spectroscopy. AB - The reduction mechanism of Pt(4+) ions confined in the channel of multi-walled carbon nanotubes was mainly investigated using X-ray absorption fine structure (XAFS) spectroscopy, with the aid of TEM, Raman, XRD and ICP-AES studies. The XAFS spectra revealed the spontaneous formation of Pt nanoparticles when H2PtCl6 was confined in multi-walled carbon nanotubes (MWCNTs). The Pt L3-edge X-ray absorption near edge structure (XANES) coupled with the C K-edge NEXAFS results indicated that the reduction of Pt(4+) from tetravalent to zerovalent was attributed to the electron transfer from MWCNTs. The Fourier transform R-space of the Pt L3-edge XAFS data displayed that the nanoconfinement effect of MWCNTs promoted the formation of Pt nanoparticles. Moreover, the Pt-Pt bond length in confined Pt nanoparticles became shorter than that of Pt in the bulk state. Furthermore, by varying the inner diameter of MWCNTs from 15 nm to 10 nm and 5 nm, the Pt-Pt bond length of nanoconfined Pt nanoparticles decreased gradually. The results clearly revealed that MWCNTs acting as enriched electron donors can continuously reduce the confined Pt ions to Pt nanoparticles, thereby showing a great potential for the design of a new type of confined nanocatalysts. PMID- 27373467 TI - Ultrathin two-dimensional layered metal hydroxides: an emerging platform for advanced catalysis, energy conversion and storage. AB - The unique properties of graphene are triggering a great deal of attention toward the family of ultrathin two-dimensional (2D) structures. Ultrathin layered metal hydroxides (LMHs) are increasingly being recognized as an important category in 2D nanomaterials, and the corresponding research has been experiencing a significant renaissance. Due to the flexible tunability of metal ions, their naturally positively charged plane and 2D anisotropy with nanometre thickness, ultrathin LMHs and their derived hybrids have shown exciting perspectives in many fields, such as catalysis, and energy storage and conversion. As for practical application, ultrathin 2D LMHs have exhibited high performances in electrocatalysis (e.g. the hydrogen and oxygen evolution reactions), photocatalysis and supercapacitors. In particular, hybrid materials based on ultrathin LMHs have proven to further improve the catalytic performance by synergistic effects derived from the hybrid interfaces. Nevertheless, studies on ultrathin LMHs are still in the infant stage and lag far behind other important 2D nanomaterials. Hence, it is essential to update the reported work in this emerging research area. In this tutorial review, we aim to summarize recent developments in ultrathin LMHs and their derived hybrids. The quite dispersed literature regarding ultrathin LMH-based materials is classified under the framework of catalysis- and energy-related properties and applications. PMID- 27373468 TI - Cavity-containing supramolecular gels as a crystallization tool for hydrophobic pharmaceuticals. AB - We present two approaches to low-molecular-weight supramolecular gels bearing hydrophobic cavities based on calixarene-containing building blocks. Gels are formed by a calixarene based tetrahydrazide gelator or a co-gel of a calixarene diammonium salt and a bis-crown ether. The calixarene hydrophobic cavity enables the complexation of hydrophobic drug molecules in a generic fashion thus providing an anchor site on the surface of the gel fibre to initiate drug crystal nucleation and growth. This technique potentially represents a route to growth of hard-to-nucleate polymorphic modifications. The co-gel comprising two components holding together by non-covalent ammonium-crown ether interaction can be easily switched back to the sol state by adding competitive binding cations. PMID- 27373469 TI - Wetting against the nap - how asperity inclination determines unidirectional spreading. AB - We have carried out wetting experiments on textured surfaces with high aspect ratio asperities in the Wenzel state. When inclination is imparted to the asperities, we observe a strictly unidirectional spreading opposite to the direction in which the asperities point. The advancing contact angle decreases markedly as inclination increases. A crude numerical analysis successfully accounts for this behaviour, highlighting the interplay between Gibbs pinning at the top of the structures and imbibition along the valleys between them. In Gibbs pinning non-linearities play a major role and we find that simple line averaging i.e. a rule of mixture - cannot account for this evolution except for weak surface perturbations, i.e. large inclinations. PMID- 27373471 TI - [Current situation and thoughts on precision medicine about the treatment of tumor in China]. AB - With United States starting"precision medical plan", it is widespread all over the world and opens a new direction to the development of medicine. Our country also starts the plan, trying to take the opportunity. At present, tumor threats human health with high incidence and mortality. In China, the incidence and mortality of tumor has been on the rise.So the tumor has become one of the most important fields of precision medicine.Precision medicine, hoping to reveal the Chinese characteristics of precision medicine, and getting the personal and social maximize health benefits are discussed in the paper. PMID- 27373472 TI - [Operation treatment method of Bismuth-Corlette III, IV hilar cholangiocarcinoma]. AB - Hilar cholangiocarcinoma (HCCA) is also known as cancer at the upper part of bile duct, perihilar cholangiocarcinoma or Klatskin tumor, etc.Bismuth-Corlette type III hilar cholangiocarcinoma refers to tumor invading right hepatic duct (IIIa) or left hepatic duct (IIIb). While Bismuth-Corlette type IV hilar cholangiocarcinoma refers to both left and right intrahepatic bile ducts being invaded. Under the premise of strictly grasping the indications of surgery, if preoperative management is conducted carefully, extended hepatic resection is a safe and feasible surgery to remove Bismuth-Corlette type III and type IV hilar cholangiocarcinoma. When conducting extended hepatic resection, right hepatectomy and combined caudate lobectomy should be conducted depending on the circumstances. Routine skeletization lymph node dissection of the hepatoduodenal ligament is performed, which could be expanded into celiac trunk, para-aortic area and the rear of pancreatic head. In the premise of radical resection, invaded vessels should be removed and then reconstructed depending on circumstances. PMID- 27373470 TI - Molecular cloning, expression and the adjuvant effects of interleukin-8 of channel catfish (Ictalurus Punctatus) against Streptococcus iniae. AB - Interleukin-8 (IL-8) as an important cytokine involving in inflammatory and immune response, has been studied as effective adjuvants for vaccines in mammals. However, there are fewer reports about the characterization and adjuvant effects of IL-8 in fish. In this study, cloning and sequence analysis of IL-8 coding region of channel catfish (Ictalurus punctatus) were conducted, mature IL-8(rtIL 8) was expressed and evaluated for its adjuvant effects on the immunoprotection of subunit vaccine encoding alpha-enolase (rENO) of Streptococcus iniae from several aspects in channel catfish. The results showed co-vaccination of rENO with rtIL-8 enhanced immune responses including humoral and cellular immunity, with higher relative percent survival(RPS,71.4%) compared with the moderate RPS of rENO alone(50%) against S. iniae infection at 4 week post vaccination. While rtIL-8 failed to maintain long-lasting immune protection, only with RPS of 26.67% in rENO + rtIL-8-vaccinated fish compared with that of rENO alone(20%) at 8 week, signifying that IL-8 hold promise for use as potential immunopotentiator in vaccines against bacterial infections in fish, whereas it is insufficient to extend the immunoprotection for long time, and further studies are required to understand the mechanisms of IL-8 used as an adjuvant and seek for more effective way to strengthen the adjuvanticity of IL-8. PMID- 27373473 TI - [Prognostic factors analysis for the long-term survival in solitary large hepatocellular carcinoma patients after hepatectomy]. AB - OBJECTIVE: To explore the prognostic factors that have affected the long-term survival of solitary large hepatocellular carcinoma (SLHCC) patients after hepatectomy. METHODS: The clinical data of 215 SLHCC patients accepted hepatectomy in the Xiangya Hospital, Central South University from January 2004 to December 2012 were retrospectively analyzed. There were 182 males and 33 females aged from 24 to 69 years(median age was 46 years). Using a variety of statistical methods, including the Kaplan-Meier estimator and the Log-rank test, the impacts of an array of clinicopathologic factors, such as age, gender, liver cirrhosis, chronic viral hepatitis, the Child-Pugh grading, microvascular invasion, macrovascular invasion and TNM staging, on the overall survival and the disease-free survival of SLHCC patients after hepatectomy were analyzed.The prognostic factors were evaluated by univariate and multivariate analyses for the long-term survival of SLHCC patients after hepatectomy. RESULTS: The whole group of patients with SLHCC showed 1-, 3-, and 5-year overall survival rates of 88.1%, 60.2%, and 41.7%, respectively, and exhibited 1-, 3-, and 5-year disease-free survival rates of 80.1%, 49.4%, and 33.6%, respectively. The 1-, 3-, and 5-year overall survival rates and disease-free survival rates of SLHCC patients with microvascular invasion were 82.0%, 45.1%, 29.0% and 69.6%, 36.1%, 23.5%, respectively. In addition, the 1-, 3-, and 5-year overall survival rates and disease-free survival rates of SLHCC patients with macrovascular invasion were 64.7%, 34.3%, 18.3% and 54.2%, 24.1%, 0, respectively. In contrast, the 1-, 3-, and 5-year overall survival rates and disease-free survival rates of SLHCC patients without vascular invasion were 95.0%, 72.3%, 51.8% and 90.1%, 60.9%, 42.9%, respectively. The results of univariate analysis indicated that liver cirrhosis, microvascular invasion, macrovascular invasion, TNM staging were hazardous factors for the overall survival of SLHCC patients(chi(2)=4.953, 8.835, 15.237, 19.789 respectively, all P<0.05); while microvascular invasion, macrovascular invasion, TNM staging were risk factors for the disease-free survival of SLHCC patients(chi(2)=12.974, 13.247, 24.516 respectively, all P<0.05). Furthermore, the multivariate analysis suggested that microvascular invasion, macrovascular invasion, TNM staging were the independent prognostic factors that have affected the overall survival and disease-free survival of SLHCC patients(all P<0.05). CONCLUSION: Microvascular invasion, macrovascular invasion and TNM staging were the independent prognostic factors for the long term survival of patients with SLHCC after hepatectomy. PMID- 27373474 TI - [Laparoscopic reoperation for recurred antireflux surgery of gastroesophageal reflux disease]. AB - OBJECTIVE: To investigate the safety and effectiveness of laparoscopic reoperation for patients with gastroesophageal reflux disease (GERD) recurred form previous anti-reflux surgery. METHODS: Totally 19 patients received laparoscopic reoperation for symptomatic and anatomic recurred GERD in Department of Gastroesophageal Reflux Disease, Rocket Force General Hospital from January 2008 to September 2015 were retrospectively analyzed. There were 12 male and 7 female patients. The average reoperation age was (48+/-14) years, the average duration of reoperation from original ones was (43+/-38) months. The patients underwent preoperative barium, endoscopy, manometry and 24-hour pH studies. Laparoscopic hiatal hernia repair plus fundoplication was carried out for reoperation. Gastroesophageal reflux related symptoms (reflux, heartburn, chest pain, chough, wheezing, chest tightness and globus sensation) before and after surgery were compared by a questionnaire. The patients' medication consumption, complications and satisfaction of the reoperation were investigated as well. The repeated measures analysis of variance was used for statistical comparison of data preoperatively and postoperatively. RESULTS: No major complication and death occurred. Six cases (32%) had complications such as diarrhea, increased passing wind, flatulence, dysphagia and abdominal pain. The GERD related symptom score of reflux, heartburn, chest pain, chough, wheezing, chest tightness and globus sensation all significantly decreased (F: 25.0 to 56.7; P: 0.000 to 0.001) after the reoperation, with 68% good outcome of all the patients. After a follow-up of (33+/-22) months after reoperation, 1 case had partial recurrence at the 3(rd) month after reoperation. For all the patients, 12 cases felt very satisfied or satisfied with the reoperation. CONCLUSION: Laparoscopic reoperation is generally effective with acceptable morbidity rates for patients with esophageal and extraesophageal symptoms recurred form previous hiatal repair and (or) fundoplication. PMID- 27373476 TI - [Developmental characteristics of various types of hand bones of Poland's syndrome]. AB - OBJECTIVE: To explore development status in different types of the hand bone and its developmental characteristics with Poland syndrome. METHODS: There were 32 cases with Poland's syndrome who accepted bilateral hand X-ray examination in Department of Hand Surgery, Beijing Jishuitan Hospital from February 2013 to August 2014.There were 24 male and 8 female patients aged from 1.0 to 15.0 years with median age of 2.4 years. Right hand deformity was 23 cases and left hand deformity was 9 cases. According to Tanner-Whitehouse skeletal age scoring system, 20 bones (radius and ulna, 7 carpal bones, 11 metacarpal and phalangeal bones) selected from the affected and contralateral limb respectively, were evaluated. Besides, hand deformity of the cases was classified into 5 types based on relevant literature. Each bone was given an individual age using the references of Greulich-Pyle chart. The average of all individual ages was taken as gross bone age, the average of individual ages of radius and ulna was taken as bone age of long bones, the average of individual ages of carpal bone was taken as bone age of carpal bones, and the average of individual age of metacarpal and phalangeal bones was taken as bone age of short bones.The delay of bone age was evaluated by correlation test, while the curve of cubic equation was used for analyzing the variance of skeletal development with age. RESULTS: The delay of long bone age of patients with Poland's syndrome in this study were 0-1.9 years ((0.5+/-0.5) years), 0-2.2 years ((0.7+/-0.5)years) for carpal bone, 0.5-2.0 years((0.6+/-0.4) years)for short bone and 0.1-1.7 years((0.6+/-0.4)years) for gross bone.Twelve cases in type II hand deformity, 15 cases in type III and 5 cases in type IV. The delay of bone ages, including long bone age, carpal bone age, short bone age and gross bone age, was not related with gender and side(all P>0.05), but related with degree of deformity(F=3.663-12.971, P=0.000-0.038). CONCLUSION: Compared with normal upper limb, the bone age in the affected limb in Poland's syndrome is delayed and it is correlated with gender, age and the extent of hand deformity and negative with side. PMID- 27373475 TI - [Clinical amalysis of left subclavian artery revascularization by stented trunk fenestration for acute Stanford type A aortic dissection]. AB - OBJECTIVE: To summarize the results and methods of left subclavian artery revascularization by stented trunk fenestration for acute Stanford type A aortic dissection. METHODS: Clinical data of 67 patients (54 male and 13 female, mean age of (50+/-10) years) underwent surgical treatment of left subclavian artery fenestration for acute Stanford A aortic dissection in Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical College between September 2008 and December 2014 were analyzed retrospectively. The origin of the left subclavian artery was in the true lumen and no dissection existed near the artery's starting. There were 18 cases of Marfan's syndrome. Preoperative echocardiography showed moderate to severe aortic regurgitation in 10 cases, and mitral regurgitation in 3 cases. Electrocardiogram showed myocardial ischemia in 5 cases. Three patients had acute impaired renal function. All the patients received total arch replacement combined with stented elephant trunk implantation. Left subclavian artery revascularization was performed by stented trunk fenestration as follows: firstly, stented elephant trunk was implanted to completely cover the left subclavian artery, then part of stented trunk's polyester lining was removed which is located at the origin of left subclavian artery. Aortic root procedures included aortic valve replacement in 2 cases, Bentall procedure in 21 cases and aortic valve sparing in 44 cases. Three patients received mitral valve repair and 6 patients received coronary artery bypass grafting. RESULTS: The cardiopulmonary bypass time, cross-clamp time, and circulatory arrest time were (179+/-32) minutes, (112+/-25) minutes, and (26+/ 10) minutes, respectively. The in-hospital mortality was 7.5% (5/67): 2 patients died of multiple organ failure, 1 patient died of acute renal failure and another 2 patients died of severe infection shock. Two patients required reexploration for root bleeding. Transient neurology dysfunction developed in 6 patients. Six patients received tracheotomy and prolonged ventilation due to pulmonary infection. All patients discharged from the hospital were followed up for 1 to 5 years. During long-term follow-up, the survival rate was 100% and 89.8% at 1 and 5 years, respectively. CT angiography was performed once per year after discharged. The left subclavian artery perfusion was good. No dissection or anastomosis leakage was identified in any case. Stroke and left limb ischemia did not develope. CONCLUSION: For acute Stanford type A aortic dissection whose origin of the left subclavian artery is in the true lumen and no dissection existed near the artery's starting, the left subclavian artery revascularization by stented trunk fenestration technique during total arch replacement combined with stented elephant trunk implantation is reliable and effective. PMID- 27373477 TI - [Radiographic study of Coflex interspinous device for lumbar spinal stenosis]. AB - OBJECTIVE: To assess the radiography change of lumbar spinal stenosis (LSS) treated with the implantation of Coflex interspinous device retrospectively. METHODS: Sixty patients (34 male and 26 female) with LSS who underwent the decompression and Coflex device implanted surgery from January 2010 to December 2013 were followed up. The mean age of the patients was 59.4 years. There were 33 cases underwent Coflex surgery and 27 cases underwent Topping-off surgery. The Coflex segment ranged from L1/2 to L4/5 (L1-2: 1, L2-3: 5, L3-4: 19, L4-5: 35). The foraminal height, foraminal width and intervertebral space height change of the Coflex segment as well as its adjacent segment were recorded pre-/post operatively and at last follow-up.Meanwhile, the Oswestry Disability Index(ODI) and Visual Analog Scale(VAS) were measured in all patient pre-/post-operatively and at last follow-up. The measurement data was recorded asx+/-s. And the independent and paired samples t-test was used to conduct the statistical analysis. RESULTS: The foraminal height(FH) increased from (19.82+/-2.38) mm to (22.28+/-2.95) mm (P<0.05) post-operatively, and the FH decreased to (19.31+/ 3.32) mm at the last follow up(P>0.05, compared to the post-operation). The average foraminal width(FW) was 11.2 mm, 11.58 mm and 11.12 mm at pre-/post operation and follow up, which had no significant different change(P>0.05). The post-operative intervertebral space height (ISH) increased from (7.84+/-1.56) mm to (10.05+/-2.39) mm(P<0.05), and the ISH decreased to (7.91+/-1.77) mm at the last follow up(P>0.05, compared to the post-operation). The amount of the decreased FH and ISH had no significant difference when comparing the Coflex segment with its adjacent (Coflex+/-1) segments (P>0.05). The lumbar lordosis(LL) was 43.13 degrees +/-15.93 degrees , 38.41 degrees +/-10.82 degrees and 43.10 degrees +/-13.21 degrees at pre-/post-operation and follow up, there was no significant difference between pre- and post-operation(P>0.05). All patients showed statistically significant improvement(P<0.05) in the clinical outcome assessed in the VAS and ODI at the time of follow up compared to the pre operation. The ODI score decreased from 65.12+/-13.56 to 9.89+/-1.77; the VAS score decreased from 8.02+/-1.81 to 1.66+/-0.51. CONCLUSIONS: Coflex device could temporarily improve the FH and ISH after operation. However, it could not maintain the improvement as the follow-up time extended. The surgical decompression is the responsible factor for the good clinical outcome but not the improvement of FH. PMID- 27373478 TI - [The clinical analysis of instrumentation failure after corrective surgery for thoracolumbar focal kyphosis]. AB - OBJECTIVE: To analyze the etiology of instrumentation failure after corrective surgery for thoracolumbar focal kyphosis, and make suggestion for treatment. METHODS: Retrospective study for 8 patients with thoracolumbar focal kyphosis who underwent surgical treatment and suffered instrumentation failure from June 2005 to December 2011 was made. The surgical procedures included pedicle subtraction osteotomy (PSO), anterior opening-posterior closing osteotomy and correction (AOPC), and posterior vertebral column resection (VCR). The reasons of instrumentation failure were analyzed and revision surgeries were performed. RESULTS: The incidence of instrumentation failure was 6.3%. The average occurrence time was 22.5 months after surgery. Except one had failure in 3 months after surgery, all cases happened after 1 year. In this series, there were 5 cases with post-tuberculosis, 2 cases with post-traumatic kyphosis and 1 case with congenital kyphosis. For the surgical procedure, 7 cases underwent VCR and 1 case AOPC. After the instrumentation failure, all cases had back pain, and 3 of them had combined neurological symptoms. The reasons or risk factors of instrumentation failure included non-fusion of bone graft, VCR procedure, sink of the titanium mesh, insufficiency of anchor sites, and more severe kyphosis. All the 8 cases were treated with revision surgery and got good results. CONCLUSIONS: The instrumentation failure of thoracolumbar focal kyphosis is relatively late occurred, and can develop with various reasons. Positive revision surgery is suggested for the instrumentation failure, and good results can be expected. PMID- 27373479 TI - [Clinical analysis of 67 cases of surgical site infection after spine surgery]. AB - OBJECTIVE: To investigate the treatment of surgical site infection(SSI) after spine surgery. METHODS: Sixty-seven patients (aged 20-77 years with mean age of 51 years) with etiologically-confirmed surgical site infection after spine surgery in Peking University Third Hospital between July 2004 and December 2012 were retrospectively analyzed. There were 39 male and 28 female patients; 47 lumbar infections, 4 thoracic infections, 7 lower cervical infections and 8 upper cervical infections; 64 early infections and 3 delayed infections; 23 superficial infections and 44 deep infections; 47 monomicrobial infections and 20 polymicrobial infections. Ninety-six strains of bacteria were identified from the bacterial culture of 67 patients. Sixty strains were gram-positive pathogenic bacteria (62.5%), and the top three species were Staphylococcus aureus, S. epidermidis and Enterococcus faecalis. The remaining 36 strains were gram negative pathogenic bacteria (37.5%), and the 3 species most predominant were Escherichia coli, Enterobacter cloacae, and Acinetobacter baumannii. All the patients with SSI were administered antibiotics. Debridement and irrigation suction was performed if little symptomatic improvement was achieved in two-to three days of antibiotics treatment, patients underwent 1-5 times of debridements (mean 1.5 times). RESULTS: One patient was dead of MRSA septicemia, whom manifested as high fever, alalia and incision swelling when the infection occurred. The patient underwent polymicrobial of pulmonary infection and urinary tract infection during the period of hospitalization, and finally died of multiple organ failure. Sixty-six cases had wound healed, and they were followed up for 25-117 months (average 70 months), no recurrence of infection was found at last follow-up. Among the 65 cases of internal fixation, 56 cases reserved the implants, while implants were removed in other 9 cases for controlling infection. CONCLUSION: Reasonable antibiotics and irrigation-suction are effective methods for managing surgical site infections after spine surgery and prevent removal of implants. PMID- 27373480 TI - [Survival analysis of surgically treated renal cell carcinoma: an analysis of 10 year data from single center]. AB - OBJECTIVE: To explore how clinical features of renal cell carcinoma (RCC) relate to cancer patients' prognosis and survival. METHODS: A total of 1 497 renal cell carcinoma patients received surgical treatments in Department of Urology, Peking Union Medical College were admitted between January 2002 and December 2012. Telephone interviews and complimentary medical records review were carried out to acquire follow-up data, including post-surgery adjuvant therapy, disease progression and survival. RESULTS: There were 1 326 of all 1 497 RCC cases successfully followed up, including 899 male and 427 female cases. The median age was 54(18) years (M(QR)). There were 1 049 T1 cases (79.11%), 139 T2 cases (10.48%), 125 T3 cases (9.43%), and 13 T4 cases (0.98%). As for types of surgery, there were 584 (44.04%) nephron-sparing surgery cases, and 742 (55.96%) radical nephrectomy cases. As for pathological subtypes, it included 1 153 (86.95%) clear cell renal cell carcinoma cases, and 173 (13.05%) non-clear cell renal cell carcinoma cases. Median length of follow-up was 43.6 months. During follow-up, 147 patients developed RCC related progression, with a median progression free survival of 18.2 months.Sixty-four patients died from RCC related progression, with a median cancer specific survival (CSS) of 27.7 months. RESULTS of data analysis showed that CSS rates of 1-, 5-, 10-year of T1 stage post-surgical RCC were 99.61%, 97.24%, 92.08%, respectively; CSS rates of 1-, 5-, 10-year of T2 stage were 98.51%, 92.01%, 85.08%, respectively; and CSS rates of 1-, 5-, 10-year of T3-4 stage were 92.40%, 77.99%, 42.56%, respectively. Multivariable Cox regression analysis showed that signs of lung metastasis, signs of bone metastasis, tumor N stage, pathological subtype, microscopic sarcomatoid changing, and types of progression were major risk factors for RCC cancer specific survival (P<0.05). CONCLUSIONS: Surgery is the primary choice of treatment in RCC. The survival is not same with different T stage. T stage affects the progression of renal cell carcinoma. N stage, lung and bone symptoms, pathological type, sarcomatoid changes and postoperative metastasis of renal cell carcinoma will affect the mortality of patients. PMID- 27373481 TI - [A multicenter study on the prognostic factors of one year outcomes in patients with poor grade intracranial aneurysm after early treatment]. AB - OBJECTIVES: To explore the one year outcome of subarachnoid hemorrhage (SAH) patients with poor grade intracranial aneurysm who underwent early treatment (within 72 hours), and to analyze the possible predictors of the prognosis. METHODS: This clinical study was a prospective, multicenter, observational registry of SAH patients with poor grade intracranial aneurysm. Data pertaining to 203 SAH patients with poor grade intracranial aneurysm between October 2010 and March 2013 from 10 medical centers. There were 100 male and 103 female patients. Neurological outcomes at 12 months after the surgery were measured using the Glasgow Outcome Scale (GOS). Genders, age, smoke, breath, herniation, aneurysm location, World Federation of Neurosurgical Societies (WFNS) grade, CT Fisher's grade, alcohol consumption, aneurysm diameter, surgical procedure and operation time were identified as possible prognostic factors, the association between possible prognostic factors and outcome were analyzed, using univariate and multivariate analysis. Univariate analysis included Wilcoxon rank sum test, Kruskal-Wallis H test and Nemenyi test, multivariate analysis included Logistic regression test. RESULTS: Among 203 patients, 94 patients were WFNS grade IV, and 109 patients were WFNS grade V; 31 patients were CT Fisher's grade 1 to 2, 172 patients were CT Fisher's grade 3 to 5. Herniation (OR=2.535, 95%CI: 1.204 to 5.339, P=0.014), WFNS grade V (OR=3.728, 95%CI: 1.972 to 7.043, P=0.000), CT Fisher's grade 3 to 5 (OR=5.641, 95%CI: 2.032 to 15.643, P=0.001), and anterior circulation location (OR=6.234, 95%CI: 1.996 to 19.472, P=0.002) were found to be independent prognostic factors of unfavorable prognosis. CONCLUSIONS: Early surgical treatment could improve the prognosis of SAH patients with poor-grade aneurysm. The patients with herniation, WFNS grade V, CT Fisher's grade 3 to 5, anterior circulation aneurysms suffered unfavorable prognosis. PMID- 27373482 TI - [Using (1)H-nuclear magnetic resonance metabolomics and gene ontology to establish pathological staging model for esophageal cancer patients]. AB - OBJECTIVES: By combining the metabolomics and computational biology, to explore the relationship between metabolic phenotype and pathological stage in esophageal cancer patients, to find the mechanism of metabolic network disturbance and develop a new method for fast preoperative clinical staging. METHODS: A prospective cohort study (from April 2013 to January 2016) was conducted. The preoperative patients from Sichuan Provincial People's Hospital, who were diagnosed with esophageal cancer from May 2013 to April 2014 were included, and their serum samples were collected to detect (1)H-nuclear magnetic resonance (NMR) metabolomics for the purpose of drawing the metabolic fingerprinting in different stages of patients with esophageal cancer. The data were processed with these methods-principal components analysis: partial least squares regression and support vector machine, for the exploration of the enzyme-gene network regulatory mechanism in abnormal esophageal cancer metabolic network regulation and to build the quantitative prediction model of esophageal cancer staging in the end. All data were processed on high-performance computing platforms Matalab. The comparison of data had used Wilcoxon test, variance analysis, chi(2) test and Fisher exact test. RESULTS: Twenty patients with different stages of esophageal cancer were included; and their serum metabolic fingerprinting could differentiate different tumor stages. There were no difference among the five teams in the age (F=1.086, P>0.05), the body mass index (F=1.035, P>0.05), the distance from the incisors to tumor (F=1.078, P>0.05). Among the patients with different TNM stages, there was a significant difference in plasma metabolome. Compared to IIB, IIIA, IVstage patients, increased levels of butanone, ethanol amine, homocysteine, hydroxy acids and estriol, together with decreased levels of glycoprotein, creatine, choline, isobutyricacid, alanine, leucine, valine, were observed inIB, IIA stage patients. Four metabolic markers (ethanol amine, hydroxy propionic acid, homocysteine and estriol) were eventually selected. gene ontology analysis showed that 54 enzymes and genes regulated the 4 key metabolic markers. The quantitative prediction model of esophageal cancer staging based on esophageal cancer NMR spectrum were established. Cross-validation results showed that the predicted effect was good (root mean square error=5.3, R(2)=0.47, P=0.036). CONCLUSIONS: The systems biology approaches based on metabolomics and enzyme-gene regulatory network analysis can be used to quantify the metabolic network disturbance of patients with advanced esophageal cancer, and to predict preoperative clinical staging of esophageal cancer patients by plasma NMR metabolomics. PMID- 27373483 TI - [Diagnosis and treatment of solid pseudopapillary neoplasms of the pancreas]. AB - Solid pseudopapillary neoplasm of the pancreas (SPN) is a rare neoplasm which primarily affects young women without specific clinical manifestation. Computed tomography and magnetic resonance imaging contribute to the preoperative diagnosis of SPN. Surgery is the main treatment approach for SPN and more research of radiation and chemotherapy is needed. Tumor diameter larger than 5 cm, tumor infiltrating nerve, vessel or adipose tissue can increase the risk of recurrence. However, these patients can still get good prognosis after surgical resection. PMID- 27373484 TI - [Progress in diagnosis and treatment of ipsilateral femoral neck and shaft fracture]. AB - Ipsilateral femoral neck and shaft fractures are rare injuries, which are often caused by high-energy trauma and combined with multiple injuries, such as thoracic and abdominal injury, head injuries, and fractures of other sites.Delayed or missed diagnosis of the ipsilateral femoral neck fracture often occurs.When patients with femoral shaft fractures caused by high-energy trauma are admitted into hospital, physical examination should be conducted carefully.In addition to femoral shaft fractures, radiographs of the ipsilater hip and knee joints should been taken, simultaneously taking into consideration the potential effect of anteversion angle on the demonstration of femoral neck fracture.Computed tomograph and magnetic resonance imaging are advised to perform if necessary to facilitate early and accurate diagnosis of ipsilateral femoral neck fracture.Comprehensive evaluation should be done based on age, physical condition, associated injuries as well as fracture site, classification and injury severity.Accordingly, proper and reasonable surgical plan is made.During the operation, anatomical reduction of the fractures, especially femoral neck fractures, should be achieved, and then fixed with appropriate internal implants.Besides, attention should also be paid to the treatment of associated injuries as well as the prevention and management of complications. PMID- 27373485 TI - Corrigendum: The changing shape of vaccination: improving immune responses through geometrical variations of a microdevice for immunization. PMID- 27373486 TI - [Exploratory factorial analysis and factorial complexity: Beyond rotations]. PMID- 27373487 TI - Insulin-like growth factor-1 receptor regulates repair of ultraviolet B-induced DNA damage in human keratinocytes in vivo. AB - The activation status of the insulin-like growth factor-1 receptor (IGF-1R) regulates the cellular response of keratinocytes to ultraviolet B (UVB) exposure, both in vitro and in vivo. Geriatric skin is deficient in IGF-1 expression resulting in an aberrant IGF-1R-dependent UVB response which contributes to the development of aging-associated squamous cell carcinoma. Furthermore, our lab and others have reported that geriatric keratinocytes repair UVB-induced DNA damage less efficiently than young adult keratinocytes. Here, we show that IGF-1R activation influences DNA damage repair in UVB-irradiated keratinocytes. Specifically, in the absence of IGF-1R activation, the rate of DNA damage repair following UVB-irradiation was significantly slowed (using immortalized human keratinocytes) or inhibited (using primary human keratinocytes). Furthermore, inhibition of IGF-1R activity in human skin, using either ex vivo explant cultures or in vivo xenograft models, suppressed DNA damage repair. Primary keratinocytes with an inactivated IGF-1R also exhibited lower steady-state levels of nucleotide excision repair mRNAs. These results suggest that deficient UVB induced DNA repair in geriatric keratinocytes is due in part to silenced IGF-1R activation in geriatric skin and provide a mechanism for how the IGF-1 pathway plays a role in the initiation of squamous cell carcinoma in geriatric patients. PMID- 27373488 TI - TNF-alpha-308/-238 polymorphisms are associated with gastric cancer: A case control family study in China. AB - BACKGROUND: Associations of TNF-alpha-308 (rs1800629) and -238 (rs361525) with gastric cancer had the inconsistent indication among different populations. METHODS: In this case-control family study, 47 families were determined with the probands diagnosed with gastric cancer (case family, n=296), accordingly 47 families without gastric cancer were matched with the case families by multivariate distribution of age, sex, social class, and pedigree size (control family, n=319). Polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) was used to identify the TNF genotype. Chi-square test was used to compare the groups regarding genotype and the allele frequencies, HWE test for Hardy-Weinberg equilibrium. RESULTS: The frequencies of TNF-alpha-308 GA and AA genotypes were significantly higher in case family than that in control family. The risk of gastric cancer was increased in GA and AA carriers in the first degree (OR=2.06, 95% CI=1.20-3.51 and OR=4.89, 95% CI=2.74-8.74), however the similar result was not found in the second degree. Helicobacter pylori infection status were significantly associated with risk of gastric cancer in first-degree relatives (OR=1.96, 95% CI=1.26-3.05) while no statistical significance was noted in the second-degree relatives. Haplotypes of TNF-alpha 308/-238 alleles, GA/GG, AA/GG and AA/GA indicated the susceptibilities to gastric cancer with OR and 95% confident intervals resulting 2.07 (1.34-3.21), 4.49 (2.74-7.33) and 4.98 (1.76-14.01) respectively. CONCLUSIONS: TNF-alpha-G308A (rs1800629) polymorphisms are associated with gastric cancer in Chinese population. Haplotypes of TNF-alpha-308/-238 GA/GG, AA/GG and AA/GA increase the susceptibilities to gastric cancer. The first-degree relatives are more likely to develop into gastric cancer with TNF-alpha-G308 polymorphisms and H. pylori positive than the second-degree are. PMID- 27373489 TI - Constitutive expression of recombinant human hyaluronidase PH20 by Pichia pastoris. AB - PH20 is known as sperm adhesion molecule 1 (SPAM1) and also has hyaluronidase function to preferentially hydrolyze the glycosidic linkage of hyaluronic acid (HA). A DNA fragment containing core domain of human PH20 gene was cloned into a constitutive expression plasmid (pGAPZalphaC) of Pichia pastoris to produce a fusion protein with alpha factor signal in the N-terminus and 6 * His as well as c-Myc tags in the C-terminus. The resulting plasmid pGAPZalphaC-PH20 was integrated into the genome of P. pastoris strain GS115. Functional recombinant human PH20 (rHuPH20) was successfully expressed and secreted by the recombinant P. pastoris transformant. Highest hyaluronidase activity of 2 mU/mL could be obtained at 3 day in an YPD culture. After purified by phenylboronic acid resin adsorption, rHuPH20 with a specific activity of 230 mU/mg was obtained. Via periodic acid-Schiff staining and zymogram analysis, the partially purified rHuPH20 was determined to be highly glycosylated to various extents with molecular mass in the range of 100-300 kDa. The enzyme showed a maximal activity at pH 5.0 but no appreciable activity at pH <=3 and pH >=8. The hyaluronidase activity could be stably maintained at 4 degrees C but lost 40% after incubating at 30 degrees C for 4 h. Both N-acetyl cysteine and glutathione showed a half maximal inhibitory concentration (IC50) of 8 mM against rHuPH20. PMID- 27373490 TI - Comparative evaluation of short-term stress of Cd(II), Hg(II), Pb(II), As(III) and Cr(VI) on anammox granules by batch test. AB - Batch experiments were conducted to investigate the short-term effects of Cd(II), Hg(II), Pb(II), As(III) and Cr(VI) on anammox activity, which are considered to be the top 5 toxic heavy metals in China. The IC50 values of Cd(II), Hg(II), Pb(II) and Cr(VI) were calculated to be 7.00, 2.33, 10.40 and 9.84 mg/L, respectively, while As(III) caused only 29.67% decrease in SAA even at the dosage of 60 mg/L. The evaluation of metal concentrations in liquid and sludge revealed that anammox biomass hold a high heavy-metal accumulation ability, which was hypothesized to be the key reason of activity inhibition. The functional groups possessed by anammox biomass and the extracellular polymeric substance (EPS) might contribute to the attachment of heavy metals. Especially, microbial reduction of Cr(VI) to Cr(III) inside the granules was discovered, which was considered to relieve the Cr(VI) inhibition under concentrations lower than 8.96 mg/L. PMID- 27373492 TI - Breast reconstruction and risk of lymphedema after mastectomy: A prospective cohort study with 10 years of follow-up. AB - OBJECTIVE: The aim of this study is to assess the incidence and risk factors for lymphedema in women submitted to mastectomy, with or without breast reconstruction. METHODS: A cohort study was performed on women submitted to mastectomy with axillary lymphadenectomy in a single center. The follow-up included clinical evaluation and arm column measurements before surgery, at 30 days, 6 months, 5 years, and 10 years after surgery. For women subjected to late reconstruction, the time of occurrence of lymphedema (before or after reconstruction) was observed. RESULTS: We followed up on 622 patients submitted to mastectomy and axillary lymphadenectomy for an average period of 57 months after surgery. In total, 94 women were submitted to breast reconstruction, 47 (8%) of them immediate and 47 (8%) late reconstructions. Incidence of lymphedema in the whole group was 33% (n = 204). Among the patients submitted to reconstruction, 28% of them developed lymphedema, on average, 93 months (CI 95%, 88-98) after surgical treatment. In women not subjected to reconstruction, 179 (34%) developed lymphedema, on average, after 106 months (CI 95%, 96-116) (p = 0.03). Breast reconstruction reduced lymphedema risk in 36% (HR = 0.64, CI 96%, 0.42-0.98, p = 0.04). After adjustment for pathological staging and radiotherapy, this was not statistically significant (HR = 0.79, CI 95%, 0.52-1.21, p = 0.28). CONCLUSION: Breast reconstruction does not increase the risk of lymphedema in long-term follow-up. PMID- 27373491 TI - Early Experience in the Management of Postoperative Lymphatic Leakage Using Lipiodol Lymphangiography and Adjunctive Glue Embolization. AB - PURPOSE: To evaluate the safety and efficacy of Lipiodol lymphangiography and 3 adjunctive N-butyl cyanoacrylate (NBCA) glue embolization techniques for the management of postoperative lymphatic leakage. MATERIALS AND METHODS: This retrospective study included 27 patients with postoperative lymphatic leakage (17 with ascites, 3 with chylothorax, 6 with lymphoceles, and 1 with a skin fistula) who underwent Lipiodol lymphangiography for diagnostic and therapeutic purposes in 3 tertiary referral centers between August 2010 and January 2016. Adjunctive glue embolization was performed as needed by using 3 different techniques: "lymphopseudoaneurysm" embolization, closest upstream lymph node embolization, or direct upstream lymphatic vessel embolization. RESULTS: Sixteen patients were observed to determine the therapeutic effect of lymphangiography, and 8 patients (50%) recovered without further embolization. In 16 patients, including 11 who underwent immediate embolization after lymphangiography and 5 who underwent delayed embolization, a total of 28 embolizations (12 lymphopseudoaneurysms, 14 lymph nodes, and 2 lymphatic vessels) were performed. The technical and clinical success rates of the adjunctive embolizations were 89% (25 of 28) and 94% (15 of 16), respectively. The overall clinical success rate was 85% (23 of 27). The median time from initial lymphangiography to recovery was 5 days. No procedure related major complications were reported. CONCLUSIONS: Lipiodol lymphangiography and adjunctive glue embolization techniques appear safe and provide promising efficacy for the management of postoperative lymphatic leakage. PMID- 27373495 TI - Revealing the morphological architecture of a shape memory polyurethane by simulation. AB - The lack of specific knowledge of the network structure in shape memory polymers (SMPs) has prevented us from gaining an in-depth understanding of their mechanisms and limited the potential for materials innovation. This paper firstly reveals the unit-cell nanoscale morphological architecture of SMPs by simulation. The phase separated architecture of a segmented shape memory polyurethane (SMPU) with a 30 wt% hard segment content (HSC, 4,4'-diphenylmethane diisocyanate (MDI) and 1,4-butanediol (BDO)) showing good shape memory properties was investigated by dissipative particle dynamics (DPD) simulations. A linked-spherical netpoint frame phase of MDI, a matrix-switch phase of polycaprolactone (PCL) and a connected-spider-like interphase for BDO were obtained for this SMPU. The BDO interphase can reinforce the MDI network. Based on these simulation results, a three-dimensional (3D) overall morphological architectural model of the SMPU can be established. This theoretical study has verified, enriched and integrated two existing schematic models: one being the morphological model deduced from experiments and the other the frame model for SMPs reported before. It can serve as a theoretical guide for smart polymeric materials design. This method for the simulation of polymer structure at the nanoscale can be extended to many areas such as photonic crystals where nanoscale self-assembly plays a vital role. PMID- 27373494 TI - How to make a sex chromosome. PMID- 27373493 TI - Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis. AB - Adenosine deaminases that act on RNA (ADARs) convert adenosine residues to inosine in double-stranded RNA. In vivo, ADAR1 is essential for the maintenance of hematopoietic stem/progenitors. Whether other hematopoietic cell types also require ADAR1 has not been assessed. Using erythroid- and myeloid-restricted deletion of Adar1, we demonstrate that ADAR1 is dispensable for myelopoiesis but is essential for normal erythropoiesis. Adar1-deficient erythroid cells display a profound activation of innate immune signaling and high levels of cell death. No changes in microRNA levels were found in ADAR1-deficient erythroid cells. Using an editing-deficient allele, we demonstrate that RNA editing is the essential function of ADAR1 during erythropoiesis. Mapping of adenosine-to-inosine editing in purified erythroid cells identified clusters of hyperedited adenosines located in long 3'-untranslated regions of erythroid-specific transcripts and these are ADAR1-specific editing events. ADAR1-mediated RNA editing is essential for normal erythropoiesis. PMID- 27373496 TI - The effects of oral glutamine on clinical and survival outcomes of non-small cell lung cancer patients treated with chemoradiotherapy. AB - PURPOSE: To assess the efficacy of oral glutamine (Gln) supplementation on clinical and survival outcomes of patients with locally advanced non-small cell lung cancer (LA-NSCLC). MATERIALS/METHODS: Between 2010 and 2014, 122 stage III NSCLC patients were retrospectively analyzed. All patients received curative intent chemoradiotherapy (CRT). Prophylactic oral Gln powder was applied at a dose of 10 g tid. Effect of oral Gln supplementation in the prevention of severe (>=grade 2-3) acute radiation-induced esophagitis (ARE) and weight loss, and their relation with overall survival (OS) and disease-free survival (DFS) was measured. RESULTS: Median follow-up was 13.14 months (range; 1.97-55.36). Fifty six (46%) patients had received oral Gln. Severe ARE was significantly lower in Gln-supplemented group (30% vs 70%; p = 0.002). Gln-free patients demonstrated a higher weight loss (p = 0.0001). In multivariate analysis hemoglobin (hb) level (<12 g/dL; p = 0.01) and nodal stage (N3; p = 0.01) were poor prognostic factors that affect OS; Weight loss (p = 0.06) and Gln-free (p = 0.05) reached nearly significant levels that poorly affect OS. Similarly, nodal stage (N3, p = 0.014) and Gln-free (p = 0.035) were poor prognostic factors that affect DFS. Weight loss (>=2%, p = 0.06) and hb level (<12 g/dL, p = 0.07) reached borderline significance that poorly affect DFS. Nodal stage (N3) was the only poor prognostic factor that affect OS and DFS in univariate analysis (p = 0.01, p = 0.009; respectively). CONCLUSION: Oral Gln supplementation significantly reduces grade 2-3 esophagitis and weight loss and also no negative impact on tumor control and survival outcomes in patients with LA-NSCLC. PMID- 27373497 TI - Indirect calorimetry in nutritional therapy. A position paper by the ICALIC study group. AB - BACKGROUND & AIMS: This review aims to clarify the use of indirect calorimetry (IC) in nutritional therapy for critically ill and other patient populations. It features a comprehensive overview of the technical concepts, the practical application and current developments of IC. METHODS: Pubmed-referenced publications were analyzed to generate an overview about the basic knowledge of IC, to describe advantages and disadvantages of the current technology, to clarify technical issues and provide pragmatic solutions for clinical practice and metabolic research. The International Multicentric Study Group for Indirect Calorimetry (ICALIC) has generated this position paper. RESULTS: IC can be performed in in- and out-patients, including those in the intensive care unit, to measure energy expenditure (EE). Optimal nutritional therapy, defined as energy prescription based on measured EE by IC has been associated with better clinical outcome. Equations based on simple anthropometric measurements to predict EE are inaccurate when applied to individual patients. An ongoing international academic initiative to develop a new indirect calorimeter aims at providing innovative and affordable technical solutions for many of the current limitations of IC. CONCLUSION: Indirect calorimetry is a tool of paramount importance, necessary to optimize the nutrition therapy of patients with various pathologies and conditions. Recent technical developments allow broader use of IC for in- and out patients. PMID- 27373498 TI - Validation of the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria for systemic sclerosis in patients from a capillaroscopy clinic. AB - OBJECTIVE: To validate the 2013 ACR/EULAR classification criteria for systemic sclerosis (SSc) in patients from a capillaroscopy clinic. METHODS: All patients attended in a capillaroscopy clinic were included. Sociodemographic and SSc related variables were collected. Using as gold standard for SSc the clinical judgement, the performance (sensitivity, specificity, predictive values, and likelihood ratios) of the 2013 ACR/EULAR criteria were analyzed. Receiver operating characteristic (ROC) curve and the area under the curve (AUC) were calculated for the global score and individual items, and the best cutoffs were obtained. RESULTS: We included 327 patients (84% women, mean age at capillaroscopy 48 years). Main reasons for capillaroscopy referral were Raynaud's phenomenon (39%) and SSc evaluation (27%). The most frequent final clinical diagnosis were SSc (32.4%) and primary Raynaud's phenomenon (25.7%). The 2013 ACR/EULAR SSc classification criteria were met by 116 patients (35.5%). Sensitivity and specificity of the new criteria were 98.1% and 94.6%, respectively, and positive and negative predictive values were 89.7% and 99.1%. The individual variables with the best sensitivity were Raynaud's phenomenon (99.1%) and abnormal nailfold capillaries (81.1%). All the individual variables, except Raynaud's phenomenon, puffy fingers and sclerodactily showed high specificity values, over 90%. The best cutoffs of the total score were >=8, >=9, and >=10, and the AUC = 0.993. CONCLUSIONS: We validated the new ACR/EULAR classification criteria for SSc in unselected patients from a capillaroscopy clinic. Global score and individual items included in the new criteria show high diagnostic accuracy and discriminatory capacity. PMID- 27373499 TI - Active peripheral inflammation is associated with pro-atherogenic lipid profile in psoriatic arthritis. AB - OBJECTIVE: The association between psoriatic arthritis (PsA) disease activity and lipid profiles has not been explored. We studied the association between active peripheral arthritis and/or enthesitis/daclylitis with lipid measurements in PsA. METHODS: We conducted a cross-sectional study of PsA patients enrolled in the Consortium of Rheumatology Researchers of North American (CORRONA) registry. Low activity was defined as Clinical Disease Activity Index (CDAI) <= 10 without enthesitis or dactylitis. Moderate-to-high peripheral disease activity was defined as CDAI > 10 and/or the presence of enthesitis/dactylitis. RESULTS: Of the 4672 patients with PsA enrolled in the CORRONA registry from June 2008 to October 2012, 725 (15.5%) had complete data on CDAI and lipid measurements. Of them, 284 (39%) patients had CDAI > 10 and/or enthesitis/dactylitis. Moderate-to high group included more women and more current smokers. Patients with moderate to-high disease activity had shorter duration of disease, and were more likely to be on prednisone, but less likely to use tumor necrosis factor (TNF) inhibitors. Moderate-to-high peripheral disease activity was associated with abnormal total cholesterol (TC) (>200mg/dl), odds ratio (OR) = 1.58; 95% CI: (1.11, 2.24); p = 0.01, and abnormal triglycerides (TG) (>150mg/dl), OR = 1.64; 95% CI: (1.16, 2.32); p = 0.005, after adjusting for gender, duration of PsA, smoking, body mass index, diabetes, modified Heath Assessment Questionnaire scores, as well as the following medications: methotrexate, other non-biologic disease modifying anti rheumatic drugs, prednisone, TNF inhibitors, cholesterol lowering medications, and fish oil. The presence of enthesitis and/or dactylitis, irrespective of CDAI scores, was associated with abnormal TC, OR = 1.64; 95% CI: (1.08, 2.48); p = 0.02. CONCLUSION: Our findings suggest an association between peripheral joint inflammation and lipid dysregulation in PsA. Further studies are needed to determine if treating PsA improves lipid profiles and cardiovascular mortality. PMID- 27373500 TI - The association of clinical parameters and ultrasound verified inflammation with patients' and physicians' global assessments in psoriatic arthritis. AB - OBJECTIVES: To study the association of clinical and/or ultrasound variables with patients' (PGA) and physicians' (EGA) global assessment of disease activity in psoriatic arthritis (PsA). The correlation of these parameters with the discordance between PGA and EGA, as well as with PGA/EGA changes over 6 months was also investigated. METHODS: Prospective study of 83 consecutive PsA patients with 2 visits scheduled 6 months apart. All patients underwent the following assessments: tender (TJC) and swollen joint count (SJC), PASI, dactylitis and Leeds enthesitis index. PGA, patients' level of pain (pain VAS), EGA, and HAQ were also recorded. Grey scale (GS) and power Doppler (PD) ultrasound were performed at 68 joints (evaluating synovia and tendons) and 14 entheses. Regression analyses were performed to assess the association of these variables with PGA and EGA. Two new variables "PGAminusEGA" and "PGAchange - EGAchange" were developed to explore the discrepancy between PGA and EGA and the consistency of PGA/EGA changes over time, respectively. RESULTS: The parameters explaining most of PGA and EGA variability were pain VAS (30.5%) and SJC (48.5%), respectively. The correlation between EGA and joint counts was stronger in patients with high vs. low levels of ultrasound verified inflammation. PGAminusEGA was mainly explained by pain and SJC. Pain was the most important predictor of PGA change whereas TJC and HAQ were more closely associated with EGA changes. "PGAchange-EGAchange" was linked to pain and SJC. Ultrasound scores were not linked with either of these variables. CONCLUSIONS: Pain VAS and joint counts are the most important clinical parameters explaining patients' and physicians' perception of disease activity, whereas the correlation of active inflammation as verified by sonography with these factors is limited. PMID- 27373501 TI - Alternation in the gap-junctional intercellular communication capacity during the maturation of osteocytes in the embryonic chick calvaria. AB - INTRODUCTION: The intercellular network of cell-cell communication among osteocytes is mediated by gap junctions. Gap junctional intercellular communication (GJIC) is thought to play an important role in the integration and synchronization of bone remodeling. To further understand the mechanism of bone development it is important to quantify the difference in the GJIC capacity of young and developmentally mature osteocytes. MATERIALS AND METHODS: We first established an embryonic chick calvaria growth model to show the growth of the calvaria in embryos at 13 to 21days of age. We then applied a fluorescence recovery after photobleaching (FRAP) technique to compare the difference in the GJIC capacity of young osteocytes with that of developmentally mature osteocytes. Finally, we quantified the dye (Calcein) diffusion from the FRAP data using a mathematic model of simple diffusion which was also used to identify simple diffusion GJIC pattern cells (fitted model) and accelerated diffusion GJIC pattern cells (non-fitted model). RESULTS: The relationship between the longest medial-lateral length of the calvaria (frontal bone) and the embryonic age fit a logarithmic growth model: length=5.144*ln(day)-11.340. The morphometric data during osteocyte differentiation showed that the cellular body becomes more spindle-shaped and that the cell body volume decreased by approximately 22% with an increase in the length of the processes between the cells. However, there were no significant differences in the cellular body surface area or in the distance between the mass centres of the cells. The dye-displacement rate in young osteocytes was significantly higher than that in developmentally mature osteocytes: dye displacement only occurred in 26.88% of the developmentally mature osteocytes, while it occurred in 64.38% of the young osteocytes. Additionally, in all recovered osteocytes, 36% of the developmentally mature osteocytes comprised non-fitted model cells while 53.19% of the young osteocytes were the non-fitted model, which indicates the active transduction of dye molecules. However, there were no statistically significant differences between the young and developmentally mature osteocytes with regard to the diffusion coefficient, permeability coefficient, or permeance of the osteocyte processes, which were 3.93+/-3.77 (*10(-8)cm(2)/s), 5.12+/-4.56 (*10(-5)cm(2)/s) and 2.99+/ 2.47 (*10(-13)cm(2)/s) (mean+/-SD), respectively. CONCLUSIONS: These experiments comprehensively quantified the GJIC capacity in the embryonic chick calvaria and indicated that the cell-cell communication capacity of the osteocytes in the embryonic chick calvaria was related to their development. PMID- 27373502 TI - Prophylactic pamidronate partially protects from glucocorticoid-induced bone loss in the mdx mouse model of Duchenne muscular dystrophy. AB - Glucocorticoids are extensively used to treat patients with Duchenne muscular dystrophy because of their ability to delay muscle damage, prolong ambulation and extend life. However, use of glucocorticoids significantly increases bone loss, fragility and fractures. To determine if antiresorptive bisphosphonates could prevent the effects of glucocorticoids on bone quality, we used dystrophic mdx mice treated with the glucocorticoid prednisone during 8weeks of rapid bone growth from 5 to 13weeks of age and treated some mice with the bisphosphonate pamidronate during the first two weeks of prednisone administration. Prednisone reduced long bone growth, decreased cortical bone thickness and area and decreased the strength of the femurs. Pamidronate treatment protected mice from cortical bone loss but did not increase bone strength. The combination of prednisone and pamidronate inhibited remodeling of metaphyseal trabecular bone with large numbers of trabeculae containing remnants of calcified cartilage. Prednisone improved muscle strength in the mdx mice and decreased serum creatine kinase with evidence of improved muscle histology and these effects were maintained in mice treated with pamidronate. PMID- 27373503 TI - Emerging therapies for the treatment of skeletal muscle wasting in chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that constitutes a major global health burden. A significant proportion of patients experience skeletal muscle wasting and loss of strength as a comorbidity of their COPD, a condition that severely impacts on their quality of life and survival. At present, the lung pathology is considered to be largely irreversible; however, the inherent adaptability of muscle tissue offers therapeutic opportunities to tackle muscle wasting and potentially reverse or delay the progression of this aspect of the disease, to improve patients' quality of life. Muscle wasting in COPD is complex, with contributions from a number of factors including inflammatory cytokines, oxidative stress, growth and anabolic hormones, nutritional status, and physical activity. In this review, we discuss current and emerging therapeutic approaches to treat muscle wasting in COPD, including a number of pharmacological therapies that are in development for muscle atrophy in other pathological states that could be of relevance for treating muscle wasting in COPD patients. PMID- 27373505 TI - Microglia activation states and cannabinoid system: Therapeutic implications. AB - Microglial cells are recognized as the brain's intrinsic immune cells, mediating actions that range from the protection against harmful conditions that modify CNS homeostasis, to the control of proliferation and differentiation of neurons and their synaptic pruning. To perform these functions, microglia adopts different activation states, the so-called phenotypes that depending on the local environment involve them in neuroinflammation, tissue repair and even the resolution of the inflammatory process. There is accumulating evidence indicating that cannabinoids (CBs) might serve as a promising tool to modify the outcome of inflammation, especially by influencing microglial activity. Microglia has a functional endocannabinoid (eCB) signaling system, composed of cannabinoid receptors and the complete machinery for the synthesis and degradation of eCBs. The expression of cannabinoid receptors - mainly CB2 - and the production of eCBs have been related to the activation profile of these cells and therefore, the microglial phenotype, emerging as one of the mechanisms by which microglia becomes alternatively activated. Here, we will discuss recent studies that provide new insights into the role of CBs and their endogenous counterparts in defining the profile of microglia activation. These actions make CBs a promising therapeutic tool to avoid the detrimental effects of inflammation and possibly paving the way to target microglia in order to generate a reparative milieu in neurodegenerative diseases. PMID- 27373504 TI - Chimeric antigen receptor-modified T cells for the treatment of solid tumors: Defining the challenges and next steps. AB - Chimeric antigen receptor (CAR) T cell therapy has shown promise in CD19 expressing hematologic malignancies, but how to translate this success to solid malignancies remains elusive. Effective translation of CAR T cells to solid tumors will require an understanding of potential therapeutic barriers, including factors that regulate CAR T cells expansion, persistence, trafficking, and fate within tumors. Herein, we describe the current state of CAR T cells in solid tumors; define key barriers to CAR T cell efficacy and mechanisms underlying these barriers, outline potential avenues for overcoming these therapeutic obstacles, and discuss the future of translating CAR T cells for the treatment of patients with solid malignancies. PMID- 27373506 TI - Preclinical and clinical studies on afatinib in monotherapy and in combination regimens: Potential impact in colorectal cancer. AB - Targeting the epidermal growth factor receptor (EGFR) with monoclonal antibodies (mAbs) or tyrosine kinase inhibitors (TKI) has been an interesting therapeutic strategy because aberrant activation of this receptor plays an important role in the tumorgenesis of many cancer types, including colorectal cancer (CRC). After the initial promising results of EGFR-targeted therapies, therapeutic resistance is a major clinical problem. In order to overcome resistance to these EGFR targeted therapies, new treatment options are necessary. In contrast to first generation EGFR inhibitors, afatinib (BIBW2992) is a second-generation irreversible ErbB family blocker that inhibits EGFR as well as HER2 and HER4. Consequently, treatment with afatinib may result in a distinct and more pronounced therapeutic benefit. Preclinical studies have reported promising results for afatinib in monotherapy as well as in combination with other drugs in CRC model systems. Furthermore, clinical studies examining afatinib as single agent and in combination therapy demonstrated manageable safety profile. Nevertheless, only limited antitumor activity has been observed in CRC patients. Although several combination treatments with afatinib have already been investigated, no optimal combination has been identified for CRC patients yet. As molecular tumor characteristics have gained increased importance in the choice of treatment, additional studies with biomarker-driven patient recruitment are required to further explore afatinib efficacy in CRC. PMID- 27373507 TI - Nanobodies(r) as inhaled biotherapeutics for lung diseases. AB - Local pulmonary delivery of biotherapeutics may offer advantages for the treatment of lung diseases. Delivery of the therapeutic entity directly to the lung has the potential for a rapid onset of action, reduced systemic exposure and the need for a lower dose, as well as needleless administration. However, formulation of a protein for inhaled delivery is challenging and requires proteins with favorable biophysical properties suitable to withstand the forces associated with formulation, delivery, and inhalation devices. Nanobodies are the smallest functional fragments derived from a naturally occurring heavy chain-only immunoglobulin. They are highly soluble, stable, and show biophysical characteristics that are particularly well suited for pulmonary delivery. This paper highlights a number of clinical and preclinical studies on antibodies delivered via the pulmonary route and describes the advantages of using Nanobodies for inhaled delivery to the lung. The latter is illustrated by the specific example of ALX-0171, a Nanobody in clinical development for the treatment of respiratory syncytial virus (RSV) infections. PMID- 27373508 TI - Regulation of amino acid transporters in pluripotent cell populations in the embryo and in culture; novel roles for sodium-coupled neutral amino acid transporters. AB - The developmental outcomes of preimplantation mammalian embryos are regulated directly by the surrounding microenvironment, and inappropriate concentrations of amino acids, or the loss of amino acid-sensing mechanisms, can be detrimental and impact further development. A specific role for l-proline in the differentiation of embryonic stem (ES) cells, a cell population derived from the blastocyst, has been shown in culture. l-proline acts as a signalling molecule, exerting its effects through cell uptake and subsequent metabolism. Uptake in ES cells occurs predominantly through the sodium-coupled neutral amino acid transporter 2, Slc38a2 (SNAT2). Dynamic expression of amino acid transporters has been shown in the early mammalian embryo, reflecting functional roles for amino acids in embryogenesis. The expression of SNAT2 and family member Slc38a1 (SNAT1) was determined in mouse embryos from the 2-cell stage through to the early post implantation pre-gastrulation embryo. Key changes in expression were validated in cell culture models of development. Both transporters showed temporal dynamic expression patterns and changes in intracellular localisation as differentiation progressed. Changes in transporter expression likely reflect different amino acid requirements during development. Findings include the differential expression of SNAT1 in the inner and outer cells of the compacted morula and nuclear localisation of SNAT2 in the trophectoderm and placental lineages. Furthermore, SNAT2 expression was up-regulated in the epiblast prior to primitive ectoderm formation, an expression pattern consistent with a role for the transporter in later developmental decisions within the pluripotent lineage. We propose that the differential expression of SNAT2 in the epiblast provides evidence for an l proline-mediated mechanism contributing to the regulation of embryonic development. PMID- 27373509 TI - Phylogenetic distribution of extracellular guanyl-preferring ribonucleases renews taxonomic status of two Bacillus strains. AB - The potential of microbial ribonucleases as promising antitumor and antiviral agents, determines today's directions of their study. One direction is connected with biodiversity of RNases. We have analyzed completed and drafted Bacillus genomes deposited in GenBank for the presence of coding regions similar to the gene of an extracellular guanyl-preferring RNase of Bacillus amyloliquefaciens (barnase). Orthologues of the barnase gene were detected in 9 species out of 83. All of these belong to "B. subtilis" group within the genus. B. subtilis itself, as well as some other species within this group, lack such types of RNases. RNases similar to barnase were also found in species of "B. cereus" group as a part of plasmid-encoded S-layer toxins. It was also found that taxonomic states of culture collection strains, which were initially described based on a limited set of phenotypic characteristics, can be misleading and need to be confirmed. Using several approaches such as matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), sequencing of genes for 16S ribosomal RNA and RNA polymerase subunit beta followed by reconstruction of phylogenetic trees, we have re-identified two RNase-secreting Bacillus strains: B. thuringiensis B-388 which should be assigned as B. altitudinis B388 and B. intermedius 7P which should be renamed as B. pumilus 7P. Therefore, small secreted guanyl-preferring RNases are the feature of "B. subtilis" group only, which is characterized by distinctive lifestyle and adaptation strategies to environment. PMID- 27373510 TI - Steroid 5-reductases are functional during early frog development and are regulated via DNA methylation. PMID- 27373511 TI - ADAR-Mediated RNA Editing Predicts Progression and Prognosis of Gastric Cancer. AB - BACKGROUD & AIMS: Gastric cancer (GC) is the third leading cause of global cancer mortality. Adenosine-to-inosine RNA editing is a recently described novel epigenetic mechanism involving sequence alterations at the RNA but not DNA level, primarily mediated by ADAR (adenosine deaminase that act on RNA) enzymes. Emerging evidence suggests a role for RNA editing and ADARs in cancer, however, the relationship between RNA editing and GC development and progression remains unknown. METHODS: In this study, we leveraged on the next-generation sequencing transcriptomics to demarcate the GC RNA editing landscape and the role of ADARs in this deadly malignancy. RESULTS: Relative to normal gastric tissues, almost all GCs displayed a clear RNA misediting phenotype with ADAR1/2 dysregulation arising from the genomic gain and loss of the ADAR1 and ADAR2 gene in primary GCs, respectively. Clinically, patients with GCs exhibiting ADAR1/2 imbalance demonstrated extremely poor prognoses in multiple independent cohorts. Functionally, we demonstrate in vitro and in vivo that ADAR-mediated RNA misediting is closely associated with GC pathogenesis, with ADAR1 and ADAR2 playing reciprocal oncogenic and tumor suppressive roles through their catalytic deaminase domains, respectively. Using an exemplary target gene PODXL (podocalyxin-like), we demonstrate that the ADAR2-regulated recoding editing at codon 241 (His to Arg) confers a loss-of-function phenotype that neutralizes the tumorigenic ability of the unedited PODXL. CONCLUSIONS: Our study highlights a major role for RNA editing in GC disease and progression, an observation potentially missed by previous next-generation sequencing analyses of GC focused on DNA alterations alone. Our findings also suggest new GC therapeutic opportunities through ADAR1 enzymatic inhibition or the potential restoration of ADAR2 activity. PMID- 27373513 TI - Hepatitis C Virus RNA Persists in Liver Explants of Most Patients Awaiting Liver Transplantation Treated With an Interferon-Free Regimen. AB - We assessed the presence of hepatitis C virus (HCV) RNA in liver explants from 39 patients awaiting liver transplantation who were treated with an interferon-free regimen and had undetectable serum HCV RNA at the time of liver transplantation. Interestingly, HCV RNA was detected in most liver explants (67%). Patients with HCV RNA-positive explants had received shorter courses of treatment, and HCV RNA was undetectable in serum for shorter periods before transplantation compared to patients with HCV RNA-negative explants (P = .014 and P = .013, respectively). Levels of HCV RNA in explants were significantly higher in patients with a relapse of HCV infection than patients who responded to treatment (P = .016), but most patients (85%) with residual HCV-RNA in the explant achieved a sustained virologic response after receiving their liver transplant. PMID- 27373512 TI - Genetic Complexity of Crohn's Disease in Two Large Ashkenazi Jewish Families. AB - BACKGROUND & AIMS: Crohn's disease (CD) is a highly heritable disease that is particularly common in the Ashkenazi Jewish population. We studied 2 large Ashkenazi Jewish families with a high prevalence of CD in an attempt to identify novel genetic risk variants. METHODS: Ashkenazi Jewish patients with CD and a positive family history were recruited from the University College London Hospital. We used genome-wide, single-nucleotide polymorphism data to assess the burden of common CD-associated risk variants and for linkage analysis. Exome sequencing was performed and rare variants that were predicted to be deleterious and were observed at a high frequency in cases were prioritized. We undertook within-family association analysis after imputation and assessed candidate variants for evidence of association with CD in an independent cohort of Ashkenazi Jewish individuals. We examined the effects of a variant in DUOX2 on hydrogen peroxide production in HEK293 cells. RESULTS: We identified 2 families (1 with >800 members and 1 with >200 members) containing 54 and 26 cases of CD or colitis, respectively. Both families had a significant enrichment of previously described common CD-associated risk variants. No genome-wide significant linkage was observed. Exome sequencing identified candidate variants, including a missense mutation in DUOX2 that impaired its function and a frameshift mutation in CSF2RB that was associated with CD in an independent cohort of Ashkenazi Jewish individuals. CONCLUSIONS: In a study of 2 large Ashkenazi Jewish with multiple cases of CD, we found the genetic basis of the disease to be complex, with a role for common and rare genetic variants. We identified a frameshift mutation in CSF2RB that was replicated in an independent cohort. These findings show the value of family studies and the importance of the innate immune system in the pathogenesis of CD. PMID- 27373515 TI - Four Approaches to Reinvigorate Learning for the 21st Century Gastroenterologist. PMID- 27373514 TI - Duodenal Bacteria From Patients With Celiac Disease and Healthy Subjects Distinctly Affect Gluten Breakdown and Immunogenicity. AB - BACKGROUND & AIMS: Partially degraded gluten peptides from cereals trigger celiac disease (CD), an autoimmune enteropathy occurring in genetically susceptible persons. Susceptibility genes are necessary but not sufficient to induce CD, and additional environmental factors related to unfavorable alterations in the microbiota have been proposed. We investigated gluten metabolism by opportunistic pathogens and commensal duodenal bacteria and characterized the capacity of the produced peptides to activate gluten-specific T-cells from CD patients. METHODS: We colonized germ-free C57BL/6 mice with bacteria isolated from the small intestine of CD patients or healthy controls, selected for their in vitro gluten degrading capacity. After gluten gavage, gliadin amount and proteolytic activities were measured in intestinal contents. Peptides produced by bacteria used in mouse colonizations from the immunogenic 33-mer gluten peptide were characterized by liquid chromatography tandem mass spectrometry and their immunogenic potential was evaluated using peripheral blood mononuclear cells from celiac patients after receiving a 3-day gluten challenge. RESULTS: Bacterial colonizations produced distinct gluten-degradation patterns in the mouse small intestine. Pseudomonas aeruginosa, an opportunistic pathogen from CD patients, exhibited elastase activity and produced peptides that better translocated the mouse intestinal barrier. P aeruginosa-modified gluten peptides activated gluten specific T-cells from CD patients. In contrast, Lactobacillus spp. from the duodenum of non-CD controls degraded gluten peptides produced by human and P aeruginosa proteases, reducing their immunogenicity. CONCLUSIONS: Small intestinal bacteria exhibit distinct gluten metabolic patterns in vivo, increasing or reducing gluten peptide immunogenicity. This microbe-gluten-host interaction may modulate autoimmune risk in genetically susceptible persons and may underlie the reported association of dysbiosis and CD. PMID- 27373516 TI - Circulating Biomarkers in Non-Small-Cell Lung Cancer: Current Status and Future Challenges. AB - Despite recent advances, non-small-cell lung cancer remains a devastating disease and carries a grim prognosis. Major contributing factors include difficulties in diagnosing the disease early in its course during the asymptomatic stage and the poor understanding of the biology underlying disease progression. Liquid biopsies, noninvasive blood tests that detect circulating biomarkers such as circulating tumor cells and tumor-derived nucleic acid fragments, are in a rapidly evolving field of research that could provide answers to both of these unmet needs. Herein, we review the relevant data concerning the diagnostic, predictive, and prognostic significance of 3 distinct but potentially complementary circulating biomarkers in non-small-cell lung cancer: circulating tumor cells, cell-free DNA, and microRNAs. PMID- 27373517 TI - A CgIFNLP receptor from Crassostrea gigas and its activation of the related genes in human JAK/STAT signaling pathway. AB - Interferon is a highly pleiotropic cytokine, once binding to its receptors, can activate JAK kinases and STAT transcription factors to initiate the transcription of genes downstream from interferon-stimulated response elements. In the present study, a cytokine receptor-like 3 molecule was selected and cloned from oyster Crassostrea gigas, which contained a fibronectin type III domain (designed CgIFNR 3). The expression pattern of CgIFNR-3 mRNA was detected in all the tested tissues including mantle, gills, hepatopancreas, muscle, and hemocytes, with the highest expression level in hemocytes. After poly (I: C) stimulation, the expression level of CgIFNR-3 in hemocytes was observed to significantly increase at 3 h (13.06-fold, p < 0.01). CgIFNR-3 was indicated to interact with CgIFNLP by in vitro GST pull-down assay, and to activate the expression of transcription factors including ISRE, STAT3 and GAS, in human Janus kinase signal transducer and activator of transcription (JAK/STAT) pathway after co-transfection in HEK 293T cells in the reporter luciferase activity assay. These results suggested that CgIFNR-3 could bind to CgIFNLP as an interferon receptor and participate in the activation of JAK/STAT pathway in human, which will benefit for intensive studies of interferon signaling pathway in mollusc. PMID- 27373518 TI - Pleiotropic effects of survivin in vascular endothelial cells. AB - OBJECTIVE: To assess the effects of survivin (SVV)in vascular endothelial cells. METHODS: In this study, we applied a gain-of-function approach and ectopically expressed SVV in rat aortic endothelial cells (RAECs) using a SVV-expressing adenovirus. The resulting SVV expression on the steady-state mRNA and protein level in RAECs was determined by reverse transcription quantitative PCR and Western blot, respectively. Cell viability, apoptosis, and migration were assessed in vitro by CCK-8 assay, flow cytometry, and transwell assay, respectively. The effect of SVV on in vivo angiogenesis was evaluated by immunohistochemistry in nude mice. Non-infected RAECs and those infected with GFP expressing control adenovirus were used as controls. RESULTS: Compared to non infected or control adenovirus-infected RAECs in vitro, SVV-expressing cells had increased viability and migratory capability, but reduced apoptosis. In vivo, SVV expressing RAECs were associated with a higher level of angiogenesis. CONCLUSION: SVV is a positive regulator of endothelial cell survival and migration, and thus, stabilizes endothelial cells and stimulates angiogenesis. PMID- 27373519 TI - Influence of co-culture on osteogenesis and angiogenesis of bone marrow mesenchymal stem cells and aortic endothelial cells. AB - Co-culture of bone forming cells and endothelial cells to induce pre vascularization is one of the strategies used to solve the insufficient vascularization problem in bone tissue engineering attempts. In the study, primary cells isolated from 2 different tissues of the same animal, rat bone marrow stem cells (RBMSCs) and rat aortic endothelial cells (RAECs) were co cultured to study the effects of co-culturing on both osteogenesis and angiogenesis. The formation of tube like structure in 2D culture was observed for the first time in the literature by the co-culture of primary cells from the same animal and also osteogenesis and angiogenesis were investigated at the same time by using this co-culture system. Co-cultured cells mineralized and formed microvasculature beginning from 14days of incubation. After 28days of incubation in the osteogenic medium, expression of osteogenic genes in co-cultures was significantly upregulated compared to RBMSCs cultured alone. These results suggest that the co-culture of endothelial cells with mesenchymal stem cells induces both osteogenesis and angiogenesis. PMID- 27373520 TI - Aberrant methylation of TRIM58 in hepatocellular carcinoma and its potential clinical implication. AB - TRIM58 (tripartite motif containing 58) has been reported as a novel methylated gene in hepatocellular carcinoma (HCC) by methylation microarrays. However, its associations with mRNA expression and clinicopathological characteristics have not been evaluated. In this study, we explored the potential clinical implications of TRIM58 methylation in HCC. We analyzed the methylation level of TRIM58 in 181 HCC tissues, 172 matched adjacent non-tumor tissues and 13 normal liver tissues using methylation-sensitive restriction enzyme based quantitative PCR and bisulfite genomic sequencing. Further, the mRNA expression level of TRIM58 was measured in 46 paired HCC and adjacent non-tumor tissues by quantitative real-time PCR. Moreover, the relationship between TRIM58 methylation and mRNA expression, the clinicopathological features, as well as prognostic value were evaluated. The results showed that TRIM58 methylation was significantly higher in HCC tissues compared with adjacent non-tumor tissues and normal liver tissues (both p<0.0001). Using 10% as the cut-off value, hypermethylation of TRIM58 was specific in HCC tissues (28.18%, 51/181), with a tendency to correlate with unfavorable disease-free survival (p=0.047). Moreover, TRIM58 expression was significantly decreased in HCC tissues compared with adjacent non-tumor tissues (p<0.0001), and showed a negative association with DNA methylation (p=0.015, rs= -0.260). Our data indicate that TRIM58 methylation is a common event in HCC and may contribute to downregulation of its mRNA expression. Furthermore, hypermethylation of TRIM58 tends to be associated with worse DFS after hepatectomy. However, the potential clinical application of TRIM58 need to be further investigated. PMID- 27373522 TI - Preperitoneal pelvic packing: Technique and outcomes. AB - Significant pelvic ring fractures are usually secondary to high-energy trauma, and when associated with other life-threatening injuries and hemodynamic instability, result in high mortality rates ranging from 40 to 60%. The major cause of death during the first 24 h after pelvic trauma is attributed to acute blood loss, with later mortality secondary to multisystem organ failure. In a majority of patients, the source of pelvic bleeding is from disruption of the presacral venous plexus and bony fracture sites, while arterial injury is present in only 10-15%. The optimal management algorithm for hemodynamically unstable patients with pelvic fractures remains controversial. The principles of care center on resuscitation, external stabilization of the pelvis, and hemorrhage control with angiography and embolization (AE) and/or preperitoneal pelvic packing (PPP). AE is effective in controlling arterial bleeding and its role in the management of hemodynamically unstable patients with pelvic fractures is supported by the EAST guidelines. However, since most patients suffer from venous bleeding, PPP can be an alternate life saving technique to control hemorrhage, especially if AE is not immediately available. PMID- 27373521 TI - Management of alternative pathology detected using CT KUB in suspected ureteric colic. AB - Acute flank pain is a common presentation to the emergency department (ED), and imaging studies play an important role in establishing an accurate diagnosis. Computed Tomography of Kidneys, Ureters, Bladder (CT KUB) has surpassed all other imaging modalities to become the gold standard in detection of ureteric calculi. The purpose of this study is to identify the range and management of alternative diagnoses established by CT KUB in patients with suspected ureteric colic. Two hundred and fifteen consecutive CT KUB examinations ordered in the ED of a tertiary-care centre for suspected ureteric colic were retrospectively reviewed. This comprised of 134 male (62.3%) and 81 female (37.7%) patients with a mean age of 53 years old. The positive detection rate for ureteric calculi in males was 43.3% compared to a lower rate for females of 29.6% (p < 0.05). Almost two-thirds of patients were discharged following CT KUB imaging, and admission rates were significantly higher in those with alternative radiological findings (p < 0.04) Alternative radiological findings occurred in 72 patients (33.5%), including 15 patients (7.0%) who had clinically important alternative pathology. The rate of clinically important alternative findings was significantly higher in males than females, 9.7% versus 2.5% respectively (p = 0.04). Surgical intervention was more common in patients with alternative radiological findings classified as gastrointestinal (18.2%) compared to non-gastrointestinal (3.6%), however this did not reach statistical significance (p = 0.07). In conclusion, significant alternative pathology was identified using CT KUB in 7% of patients with suspected ureteric colic. The low rates of detection of ureteric calculi and significant alternative pathology in female patients suggests a more thorough clinical assessment is warranted to improve their management, prior to ordering investigations with exposure to radiation. PMID- 27373523 TI - Commentary to: PREvention STudy On preventing or reducing disability from musculoskeletal complaints in music school students (PRESTO): protocol of a randomised controlled trial. PMID- 27373524 TI - Commentary to: A workplace exercise versus health promotion intervention to prevent and reduce the economic and personal burden of non-specific neck pain in office personnel: protocol of a cluster-randomised controlled trial. PMID- 27373525 TI - Commentary to: Effect of Schroth exercises on curve characteristics and clinical outcomes in adolescent idiopathic scoliosis: protocol for a multicentre randomised controlled trial. PMID- 27373526 TI - Stroke4Carers: training modules to help the carers of people following stroke. PMID- 27373527 TI - Creating a lesion-specific "roadmap" for ambulatory care following surgery for complex congenital cardiac disease. AB - Over the past 20 years, the successes of neonatal and infant surgery have resulted in dramatically changed demographics in ambulatory cardiology. These school-aged children and young adults have complex and, in some cases, previously unexpected cardiac and non-cardiac consequences of their surgical and/or transcatheter procedures. There is a growing need for additional cardiac and non cardiac subspecialists, and coordination of care may be quite challenging. In contrast to hospital-based care, where inpatient care protocols are common, and perioperative expectations are more or less predictable for most children, ambulatory cardiologists have evolved strategies of care more or less independently, based on their education, training, experience, and individual styles, resulting in highly variable follow-up strategies. We have proposed a combination proactive-reactive collaborative model with a patient's primary cardiologist, primary-care provider, and subspecialists, along with the patient and their family. The goal is to help standardise data collection in the ambulatory setting, reduce patient and family anxiety, increase health literacy, measure and address the non-cardiac consequences of complex cardiac disease, and aid in the transition to self-care as an adult. PMID- 27373528 TI - Research & development in the dark: what does it take to make one medicine? And what could it take? AB - Earlier this year a series of advertisements appeared in London's Westminster tube stations asking viewers to consider a seemingly simple question, 'what does it take to make one medicine?' But as it turns out, this question is not so simple to answer. In this commentary we highlight some key considerations and questions on what it takes to make one medicine, and what it could take to develop medicines that meet people's health needs and are accessible and affordable for all who need them. PMID- 27373529 TI - Staffing for infectious diseases, clinical microbiology and infection control in hospitals in 2015: results of an ESCMID member survey. AB - We aimed to assess the current status of infectious diseases (ID), clinical microbiology (CM) and infection control (IC) staffing in hospitals and to analyse modifiers of staffing levels. We conducted an Internet-based survey of European Society of Clinical Microbiology and Infectious Diseases members and affiliates, collecting data on hospital characteristics, ID management infrastructure, ID/IC related activities and the ratio of physicians per 100 hospital beds. Regression analyses were conducted to examine factors associated with the physician-bed ratio. Five hundred sixty-seven hospital responses were collected between April and June 2015 from 61 countries, 81.2% (384/473) from Europe. A specialized inpatient ward for ID patients was reported in 58.4% (317/543) of hospitals. Rates of antibiotic stewardship programmes (ASP) and surveillance activities in survey hospitals were high, ranging from 88% to 90% for local antibiotic guidelines and 70% to 82% for programmes monitoring hospital-acquired infections. The median ID/CM/IC physician per 100 hospital beds ratio was 1.12 (interquartile range 0.56-2.13). In hospitals performing basic ASP and IC (including local antibiotic guidelines and monitoring device-related or surgical site infections), the ratio was 1.21 (interquartile range 0.57-2.14). Factors independently associated with higher ratios included compliance with European Union of Medical Specialists standards, smaller hospital size, tertiary-care institution, presence of a travel clinic, beds dedicated to ID and a CM unit. More than half of respondents estimated that additional staffing is needed for appropriate IC or ID management. No standard of physician staffing for ID/CM/IC in hospitals is available. A ratio of 1.21/100 beds will serve as an informed point of reference enabling ASP and infection surveillance. PMID- 27373530 TI - A single session of exercise as a modulator of short-term learning in healthy individuals. AB - BACKGROUND: A single session of aerobic exercise is linked to faster motor responses; however, the effect on rate of short-term learning is less clear. The objective was to evaluate the influence of a single bout of aerobic exercise on the rate of short-term acquisition of a shape-letter association task requiring a motor response. METHODS: 23 [11 females, age 20.8+/-2.7years] healthy young adults were evaluated using a randomly assigned crossover design which was counterbalanced for order before and after moderate (exercise) and light (control) intensity cycle ergometry. Participants performed 3 blocks, with each block consisting of one round of training and testing. During training, participants were tasked with learning 6 unique shape-letter associations. Subsequent testing required a key press response to a visually presented shape pattern. Response time and error rates were used to assess acquisition over the 3 blocks of testing. RESULTS: Mean response time was faster post-exercise relative to the other testing periods, and approached statistical significance compared to post-control (p<0.07). However, no significant difference in response time reduction (difference between test block 1 and test block 3) was identified between the four evaluations (pre and post the exercise and control conditions). Error rate reduction (test block 1 minus test block 3) revealed that individuals had the smallest change in error rate post-exercise (p<0.05). Follow-up analyses revealed fewer errors in test block 1 and test block 2 post-exercise which approached statistical significance (p=0.06) suggesting near-perfect error rates were obtained after only 2 testing blocks post-exercise compared to 3 blocks in the other testing periods. CONCLUSIONS: Support for augmentation of short-term learning was mixed as errors were reduced post-exercise while response time was not different between evaluations. Future work should include neurophysiological evaluation and a retention test to better elucidate the influence of aerobic exercise on rate of short-term learning. PMID- 27373531 TI - Traumatic brain injury accelerates amyloid-beta deposition and impairs spatial learning in the triple-transgenic mouse model of Alzheimer's disease. AB - Several pathological and epidemiological studies have demonstrated a possible relationship between traumatic brain injury (TBI) and Alzheimer's disease (AD). However, the exact contribution of TBI to AD onset and progression is unclear. Hence, we examined AD-related histopathological changes and cognitive impairment after TBI in triple transgenic (3*Tg)-AD model mice. Five- to seven-month-old 3*Tg-AD model mice were subjected to either TBI by the weight-drop method or a sham treatment. In the 3*Tg-AD mice subjected to TBI, the spatial learning was not significantly different 7 days after TBI compared to that of the sham-treated 3*Tg-AD mice. However, 28 days after TBI, the 3*Tg-AD mice exhibited significantly lower spatial learning than the sham-treated 3*Tg-AD mice. Correspondingly, while a few amyloid-beta (Abeta) plaques were observed in both sham-treated and TBI-treated 3*Tg-AD mouse hippocampus 7 days after TBI, the Abeta deposition was significantly greater in 3*Tg-AD mice 28 days after TBI. Thus, we demonstrated that TBI induced a significant increase in hippocampal Abeta deposition 28 days after TBI compared to that of the control animals, which was associated with worse spatial learning ability in 3*Tg-AD mice. The present study suggests that TBI could be a risk factor for accelerated AD progression, particularly when genetic and hereditary predispositions are involved. PMID- 27373532 TI - Electrophysiological mechanisms of biased response to smoking-related cues in young smokers. AB - Cigarette smoking during young adult may result in serious health issues in later life. Hence, it is extremely necessary to study the smoking neurophysiological mechanisms in this critical transitional period. However, few studies revealed the electrophysiological mechanisms of cognitive processing biases in young adult smokers. In present study, nineteen young smokers with 12h abstinent and 19 matched nonsmokers were recruited. By employing event-related potentials (ERP) measurements during a smoking cue induced craving task, electrophysiological brain responses were compared between the young adult smokers and nonsmokers. The Slow Positive Wave (SPW) amplitude of smoking-related cues was enhanced in young adult smokers compared with nonsmokers. In addition, increased P300/SPW component of smoking-related cues relative to neutral cues were found in young adult smokers. Meanwhile, a positive correlation between Cigarette Per Day (CPD) and the amplitude of ERPs wave (P300/SPW) at anterior (Fz), central (Cz) were observed in young adult smokers. Our findings provided direct electrophysiological evidence for the cognitive processing bias of smoking cue and may shed new insights into the smoking behavior in young adult smokers. PMID- 27373533 TI - Microinjection of acetylcholine into cerebellar fastigial nucleus induces blood depressor response in anesthetized rats. AB - It is well known that the cerebellar fastigial nucleus (FN) is involved in cardiovascular modulation, and has direct evidence of cholinergic activity; however, whether and how acetylcholine (ACh) in the FN modulates blood pressure has not been investigated. In this study, we analyzed mean arterial pressure, maximal change in mean arterial pressure, and the reaction time of blood pressure changes after microinjection of cholinergic reagents into the FN in anesthetized rats. The results showed that ACh evoked a concentration-dependent (10, 30 and 100mM) effect on blood pressure down-regulation. The muscarinic ACh (mACh) receptor antagonist atropine, but not the nicotinic ACh (nACh) receptor antagonist mecamylamine, blocked the ACh-mediated depressor response. The mACh receptor agonist oxotremorine M, rather than nACh receptor agonist nicotine, mimicked the ACh-mediated blood pressure decrease in a dose-dependent manner (10, 30 and 100mM). These results indicate that cholinergic input in the cerebellar FN exerts a depressor effect on systemic blood pressure regulation, and such effects are substantially contributed by mACh rather than nACh receptors, although the precise mechanism concerning the role of mACh receptor in FN-mediated blood pressure modulation remains to be elucidated. PMID- 27373534 TI - Pseudotenacibaculum haliotis gen. nov., sp. nov., a new member within the Tenacibaculum-Polaribacter clade of the family Flavobacteriaceae, isolated from the intestine of adult abalones, Haliotis diversicolor and H. discushannai. AB - Two rod-shaped marine bacterial strains named FDZSB0410T and FDZWPB0420, were isolated from the intestine of two adult abalone species, Haliotis diversicolor and Haliotis discushannai, respectively. The strains were non-flagellated, motile by gliding, oxidase-positive but catalase-negative, and agar-degrading. The two strains had identical 16S rRNA gene sequences with the highest sequence similarity less than 96.0 % with species of the genera Tenacibaculumand Polaribacter within the family Flavobacteriaceae. Phylogenetic analysis indicated the strains represented an independent cluster neighbouring with the species of the genera Tenacibaculum and Polaribacter. Strain FDZSB0410T can grow under conditions at 15 to 37 degrees C with optimum of 30 degrees C, salinity range from 3 to 4 % (NaCl, w/v) with optimum of 3 %, and pH range from 7 to 8 with optimum of pH 7. The predominant fatty acids of strain FDZSB0410T consisted of iso-C15 : 0, iso-C15 :1 G, summed feature 3 (comprising C16 : 1omega7c/C16 : 1omega6c), iso-C13 : 0, iso-C17 : 0 3-OH, and iso-C15 : 0 3-OH. The ubiquinone system detected was MK-6. The flexirubin pigment was absent, but the carotenoid was present. The polar lipids were identified as aminolipid, glycolipid, phosphatidylglycerol, an unknown phospholipid and four unknown lipids. The DNA G+C content was 35.3 mol%. On the basis of the genotypic and phenotypic characterizations, strain FDZSB0410T and strain FDZWPB0420 represent a novel species of a new genus in the family Flavobacteriaceae, for which the name Pseudotenacibaculum haliotis gen. nov., sp. nov. is proposed. The type strain of the type species is FDZSB0410T (=KCTC 52127T=MCCC 1A01897T). PMID- 27373535 TI - Stent migration and bail-out strategies. AB - Stent migration is an inherent complication of stent deployment. A number of factors are responsible for this dreaded complication. The stent may eventually migrate to the heart or lungs or in the process of migration damage structures en route to its final destination. A number of techniques are available to bail out interventionalists if such a situation should arise. Occasionally a wait and watch approach may be prudent. PMID- 27373536 TI - Vascular access scenario in Italy: evolution and comparison by two surveys (1998 2013). AB - PURPOSE: Dialysis settings have generally improved over the last decades, but the vascular access setting did not see significant advances and experienced a progressive worsening in epidemiology and clinical features. The aim of the study was to describe and compare evolution of vascular access in Italy over time. METHODS: A national survey implemented in Italy last year is presented and compared to a previous survey performed in 1998. Present survey collected data from almost 50% of centers involved in vascular access. RESULTS: The nephrologist participates in the management of vascular access in 97% of centers. Almost 40% of centers declare more than 40% of central venous catheters (CVCs) at first dialysis with maximum value being 60%. Prevalence of CVCs is greater than 20% in chronic prevalent patients in 38.8% of centers. According to the 2013 survey, CVCs account for 51.6% of procedures, while arteriovenous fistulae (AVF) and prostheses represent 42.4% and 6%, respectively. Nephrologists perform 73% of procedures on CVCs.From 1998 to 2013, a sharp increase in CVC prevalence was seen, in both incident and prevalent dialysis patients. This activity, mostly due to CVC management, is almost completely carried by nephrologists. DISCUSSION: The variability in CVC utilization among centers suggests the lack of a shared policy in patients and access coupling. Quantitative criteria should be used to reduce inappropriate strategy in vascular access creation. Since this activity in Italy is organized at a local level without a shared organizational model, we should inquire whether a system managed so well in the past should now be rebuilt on the model of organ transplantation. PMID- 27373537 TI - The dwell time and survival rates of PICC placement after balloon angioplasty in patient with unexpected central venous obstruction. AB - PURPOSE: To evaluate the dwell time and actual survival rates of peripherally inserted central catheter (PICC) placements after balloon angioplasty in patients with unexpected central venous obstructions. MATERIALS AND METHODS: Data were obtained on all PICC insertions performed in a tertiary care hospital from August 2008 to December 2013. Thirty-five PICCs attempted after balloon angioplasty in 25 patients (15 male and 10 female patients; mean age, 63 years). Fisher's exact test was used to test for differences in reasons for catheter removal between the groups of patients with stenosis or obstructions. Survival curves for PICC dwell time of all patients, stenosis group, and obstruction group were generated separately using Kaplan-Meier survival analysis and compared with log-rank tests. RESULTS: There were a total 21 obstructions and 14 stenoses. The overall technical success rate of PICC placement after balloon angioplasty was 94% (33 of 35 procedures). The PICC dwell time was determined for 27 PICCs and ranged from 4 to 165 days (mean, 39.6 days). Among all PICCs, 16 were removed early, resulting in an actual survival rate of 40.7% (11 of 27 PICCs). There were no significant differences in reasons for catheter removal between the stenosis and obstruction groups (p = 0.24). The dwell times for both groups were not significantly different by Kaplan-Meier analysis (p = 0.54). CONCLUSIONS: PICC placement after balloon angioplasty is a good treatment option for patients with unexpected central venous lesions, and offers high technical success rates. The actual survival rate was relatively lower (40.7%) than that from previous studies. PMID- 27373538 TI - Effector-Triggered Immunity Determines Host Genotype-Specific Incompatibility in Legume-Rhizobium Symbiosis. AB - Symbiosis between legumes and rhizobia leads to the formation of N2-fixing root nodules. In soybean, several host genes, referred to as Rj genes, control nodulation. Soybean cultivars carrying the Rj4 gene restrict nodulation by specific rhizobia such as Bradyrhizobium elkanii We previously reported that the restriction of nodulation was caused by B. elkanii possessing a functional type III secretion system (T3SS), which is known for its delivery of virulence factors by pathogenic bacteria. In the present study, we investigated the molecular basis for the T3SS-dependent nodulation restriction in Rj4 soybean. Inoculation tests revealed that soybean cultivar BARC-2 (Rj4/Rj4) restricted nodulation by B. elkanii USDA61, whereas its nearly isogenic line BARC-3 (rj4/rj4) formed nitrogen fixing nodules with the same strain. Root-hair curling and infection threads were not observed in the roots of BARC-2 inoculated with USDA61, indicating that Rj4 blocked B. elkanii infection in the early stages. Accumulation of H2O2 and salicylic acid (SA) was observed in the roots of BARC-2 inoculated with USDA61. Transcriptome analyses revealed that inoculation of USDA61, but not its T3SS mutant in BARC-2, induced defense-related genes, including those coding for hypersensitive-induced responsive protein, which act in effector-triggered immunity (ETI) in Arabidopsis. These findings suggest that B. elkanii T3SS triggers the SA-mediated ETI-type response in Rj4 soybean, which consequently blocks symbiotic interactions. This study revealed a common molecular mechanism underlying both plant-pathogen and plant-symbiont interactions, and suggests that establishment of a root nodule symbiosis requires the evasion or suppression of plant immune responses triggered by rhizobial effectors. PMID- 27373539 TI - Breeding system diversification and evolution in American Poa supersect. Homalopoa (Poaceae: Poeae: Poinae). AB - BACKGROUND AND AIMS: Poa subgenus Poa supersect. Homalopoa has diversified extensively in the Americas. Over half of the species in the supersection are diclinous; most of these are from the New World, while a few are from South-East Asia. Diclinism in Homalopoa can be divided into three main types: gynomonoecism, gynodioecism and dioecism. Here the sampling of species of New World Homalopoa is expanded to date its origin and diversification in North and South America and examine the evolution and origin of the breeding system diversity. METHODS: A total of 124 specimens were included in the matrix, of which 89 are species of Poa supersect. Homalopoa sections Acutifoliae, Anthochloa, Brizoides, Dasypoa, Dioicopoa, Dissanthelium, Homalopoa sensu lato (s.l.), Madropoa and Tovarochloa, and the informal Punapoa group. Bayesian and parsimony analyses were conducted on the data sets based on four markers: the nuclear ribosomal internal tanscribed spacer (ITS) and external transcribed spacer (ETS), and plastid trnT-L and trnL F. Dating analyses were performed on a reduced Poa matrix and enlarged Poaceae outgroup to utilize fossils as calibration points. A relaxed Bayesian molecular clock method was used. KEY RESULTS: Hermaphroditism appears to be pleisiomorphic in the monophyletic Poa supersect. Homalopoa, which is suggested to have originated in Eurasia 8.4-4.2 million years ago (Mya). The ancestor of Poa supersect. Homalopoa radiated throughout the New World in the Late Miocene-Early Pliocene, with major lineages originating during the Pliocene to Pleistocene (5-2 Mya). Breeding systems are linked to geographic areas, showing an evolutionary pattern associated with different habitats. At least three major pathways from hermaphroditism to diclinism are inferred in New World Homalopoa: two leading to dioecism, one via gynodioecism in South America and another directly from hermaphroditism in North America, a result that needs to be checked with a broader sampling of diclinous species in North America. A third pathway leads from hermaphroditism to gynomonoecism in Andean species of South America, with strictly pistillate species evolving in the highest altitudes. CONCLUSIONS: Divergence dating provides a temporal context to the evolution of breeding systems in New World Poa supersect. Homalopoa The results are consistent with the infrageneric classification in part; monophyletic sections are confirmed, it is proposed to reclassify species of sect. Acutifoliae, Dasypoa and Homalopoa s.l. and it is acknowledged that revision of the infrageneric taxonomy of the gynomonoecious species is needed. PMID- 27373541 TI - "They made me go through like weeks of appointments and everything": Documenting women's experiences seeking abortion care in Yukon territory, Canada. AB - BACKGROUND: Abortion has been legal without restriction in Canada since 1988 and is recognized as a medically necessary service. However, research indicates that women still face numerous barriers to accessing care, challenges that are amplified for women living in rural, remote and northern regions in Canada. OBJECTIVES: This qualitative study aimed to document women's experiences seeking and obtaining abortion services while residing in Yukon Territory, identify financial and personal costs and explore avenues through which services could be improved. METHODS: We conducted 16 in-depth semi-structured phone interviews with women who accessed abortion services on/after January 1, 2005, while residing in the Yukon. We employed an iterative multiphase analytic approach centering on content and themes, using both inductive and deductive techniques. RESULTS: With the Yukon's sole facility offering first trimester abortions twice a month, women experienced difficulty navigating a fragmented process and long wait times. Women found the process of attending multiple pre-procedure appointments at multiple locations with multiple health care providers, all while enduring pregnancy symptoms and handling other life commitments, physically, financially and emotionally taxing. CONCLUSION: Efforts to streamline the process of obtaining an abortion and providing women with more information at the first point of contact would improve service access and quality. Mifepristone has the potential to improve access for rural and remote populations, reduce wait times and alleviate privacy concerns, but only if the medication abortion regimen is affordable and available at a range of service delivery points and provision requirements are aligned with the global evidence. IMPLICATIONS: By documenting women's experiences, the identified barriers and outlined suggestions for improvement offer realistic avenues through which current abortion services in Yukon Territory can be modified in order to increase access. This study highlights future reproductive health care initiatives that warrant prioritization in Canada's North. PMID- 27373540 TI - Medications to ease intrauterine device insertion: a systematic review. AB - BACKGROUND: Potential barriers to intrauterine device (IUD) use include provider concern about difficult insertion, particularly for nulliparous women. OBJECTIVE: This study aims to evaluate the evidence on the effectiveness of medications to ease IUD insertion on provider outcomes (i.e., ease of insertion, need for adjunctive insertion measures, insertion success). SEARCH STRATEGY: We searched the PubMed database for peer-reviewed articles published in any language from database inception through February 2016. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that examined medications to ease interval insertion of levonorgestrel-releasing IUDs and copper T IUDs. RESULTS: From 1855 articles, we identified 15 RCTs that met our inclusion criteria. Most evidence suggested that misoprostol did not improve provider ease of insertion, reduce the need for adjunctive insertion measures or improve insertion success among general samples of women seeking an IUD (evidence Level I, good to fair). However, one RCT found significantly higher insertion success among women receiving misoprostol prior to a second IUD insertion attempt after failed attempt versus placebo (evidence Level I, good). Two RCTs on 2% intracervical lidocaine as a topical gel or injection suggested no positive effect on provider ease of insertion (evidence Level I, good to poor), and one RCT on diclofenac plus 2% intracervical lidocaine as a topical gel suggested no positive effect on provider ease of insertion (evidence Level I, good). Limited evidence from two RCTs on nitric oxide donors, specifically nitroprusside or nitroglycerin gel, suggested no positive effect on provider ease of insertion or need for adjunctive insertion measures (evidence Level I, fair). CONCLUSIONS: Overall, most studies found no significant differences between women receiving interventions to ease IUD insertion versus controls. Among women with a recent failed insertion who underwent a second insertion attempt, one RCT found improved insertion success among women using misoprostol versus placebo. PMID- 27373542 TI - Home or office etonogestrel implant insertion after pregnancy: a randomized trial. AB - OBJECTIVES: To evaluate whether home visits for contraceptive implant insertion result in an increase in postpartum uptake compared to clinic insertion and to assess the feasibility of home insertions. STUDY DESIGN: We randomized women within 10 weeks of a birth or dilation and curettage (D&C) for abortion or miscarriage to home or standard office insertion. The primary outcome was successful insertion of the implant. To achieve 80% power to detect a 40% difference in visit attendance, 20 women were assigned to each group. The secondary outcome was attendance of the 4-week postpartum visit. RESULTS: From June 2013 through February 2014, we screened 45 women and 40 were randomly assigned to home and office insertion visits. We enrolled 37 postpartum women and 3 women post-D&C. Because of the significant under enrollment of the latter, we chose to report results of only the postpartum women. The results were similar whether we included or excluded post-abortion women. A majority of women desired a home visit for their implant insertion appointment at time of enrollment. Postpartum appointment attendance rates were similar between home and office visits at 53% and 50% (p=1.00), respectively. Home visits resulted in a trend toward increased implant uptake [12/19 (63%) vs 6/18 (33%), p=.10]. CONCLUSION: Home insertion of the contraceptive implant may be a feasible option. Future studies that examine the feasibility and uptake in both postpartum and post-D&C women are warranted. IMPLICATIONS: Women reported preference for home insertion visits in this pilot study. We also showed that a greater proportion of women received the etonogestrel implant at a home visit compared to the current standard of care, which may warrant larger studies that would have sufficient power to evaluate smaller differences. PMID- 27373543 TI - Contraceptive practices among women: the second Australian study of health and relationships. AB - OBJECTIVE: To document the use of contraception by a representative sample of Australian women aged 16-49 years and compare it with 2001-2002. METHODS: Women were asked about their use of contraception and method used or reason for non-use during computer-assisted telephone interviews in 2012-2013. Women were sampled by random digit dialling of landline and mobile phones (participation rate 67.2%). RESULTS: Of a weighted sample of 5654 heterosexually active women interviewed 81% were using a method of contraception including sterilisation; this amounts to 66% of all women aged 16-49. Of those who were not using a method, 42% were pregnant or wanted a baby, 25% said they or their partners were infertile, 5% were currently not having intercourse, 3% were past menopause and 25% were apparently at risk of unintended pregnancy. Of those who used a method, 33% used oral contraceptives, 30% condoms and 19% sterilisation as their primary method. Use of condoms, intrauterine devices, implants and emergency contraception has increased since 2002, and use of sterilisation has fallen. Method used varied by age group, location, occupational group, relationship status and parity. A third of women had ever used emergency contraception, with the highest rate among women in their 20s. CONCLUSION: Australian women have access to a wide range of effective contraceptive methods. IMPLICATIONS: Given the high levels of use, most unintended pregnancies in Australia are likely to be attributable to method failure or inconsistent use. PMID- 27373544 TI - Parental social networks during childhood and offspring depression in early adulthood: a lifecourse approach. AB - BACKGROUND: Little is known on how parental social relationships may affect their children's mental health. We sought to examine the relation between parental social relationship characteristics and subsequent offspring depression in young adulthood. METHODS: We used 2009 Trajectoires Epidemiologiques en Population (TEMPO) study data from 1087 French young adults ages 22 to 35 and parental data from the corresponding Gaz et Electricite (GAZEL) study in 1991. Multivariable logistic regression was used to examine parental social networks, quality of parental relationships, and reciprocity of parental social support measured in 1991 in relation to offspring depression in young adulthood measured using the Adult Self Report in 2009. Analyses were stratified by participant sex. RESULTS: In adjusted models, daughters of parents who reported giving more support to others than they received had 1.72 higher odds (95% CI, 1.09-2.70) of depression in young adulthood. Daughters of parents who were unsatisfied with their social relationships had 2.14 (95% CI, 1.22-3.76) higher odds of depression. Among male participants, there was no statistically significant association between parental relationship satisfaction, reciprocity of parental exchanges, and depression. CONCLUSIONS: Parental relationships during mid-childhood have long-term associations with offspring depression. Results suggest that enhancing social support for parents may have positive implications for their children's mental health. PMID- 27373545 TI - The role of microRNAs in respiratory viral infection: friend or foe? AB - MicroRNAs (miRNAs) have emerged as a class of regulatory RNAs in host-pathogen interactions. Aberrant miRNA expression seems to play a central role in the pathology of several respiratory viruses, promoting development and progression of infection. miRNAs may thus serve as therapeutic and prognostic factors for respiratory viral infectious disease caused by a variety of agents. We present a comprehensive review of recent findings related to the role of miRNAs in different respiratory viral infections and discuss possible therapeutic opportunities aiming to attenuate the burden of viral infections. Our review supports the emerging concept that cellular and viral-encoded miRNAs might be broadly implicated in human respiratory viral infections, with either positive or negative effects on virus life cycle. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27373546 TI - They Sell Skulls Online?! A Review of Internet Sales of Human Skulls on eBay and the Laws in Place to Restrict Sales. AB - Internet sales of human remains occur despite the existence of laws prohibiting such action in most jurisdictions. The most popular public platform for online sales, eBay, allows users to postskeletal material for sale, largely anonymously and without much fear of legal repercussions. This survey of skeletal sales was conducted 10 years after the first article published about online human remains sales. A review of current laws reveals that, while many states have laws that restrict any sale of human remains, those laws have questionable deterrent effect. Assessing the skeletal material posted for sale provides law enforcement agencies with a necessary starting point to curtail the sale of human remains through enforcement of existing laws. Ultimately, the goal is to stem the commodification of such items and to recover skeletal material, especially that which may be of archaeological or forensic significance, and provide the proper final disposition for such material. PMID- 27373547 TI - Prospective Memory Performance in Persons With Schizophrenia and Bipolar Disorder and Healthy Persons. AB - PURPOSE: There is a paucity of studies comparing prospective memory (PM) impairment between persons with schizophrenia and bipolar disorder. The aim of this study was to directly compare PM performances of these two groups and healthy controls. DESIGN AND METHODS: A total of 44 persons with schizophrenia and 76 with bipolar disorder, and 44 healthy controls formed the study sample. FINDINGS: Patients were found to be impaired in PM relative to controls and the two patient groups showed similar level of PM performance after controlling confounding sociodemographic and clinical variables. PRACTICE IMPLICATIONS: The findings add to the evidence concerning the neurocognitive similarity between cohorts of schizophrenia and bipolar disorder with respect to PM. Rehabilitative effort in PM remedies for both patient groups is warranted. PMID- 27373549 TI - Liquid chromatography-quadrupole-time-of-flight mass spectrometry screening procedure for urine samples in forensic casework compared to gas chromatography mass spectrometry. AB - This work represents the development, validation, and application of a liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS) screening method for the detection of pharmaceutical substances and illicit drugs (acidic, basic, and neutral organic drugs) in urine samples. Time-of-flight mass spectrometry was performed using an LC-Triple TOF 5600 system with electrospray ionization operated in both positive and negative mode, respectively. The limits of detection (LODs), determined for 34 substances, were < 10 ng/mL for 91% of the compounds. The limits of quantitation (LOQs) were < 20 ng/mL for 91% of the substances. The identification of the compounds was based on exact mass (< +/- 5 ppm), retention time (<2%) if available, isotopic pattern fit (<10%) and library hit (>70%). These four parameters served as identification criteria and are discussed according to their role in identifying compounds even without reference substances. In routine casework, two in-house XIC (extracted ion chromatogram) lists, consisting of 456 protonated and 26 deprotonated compounds were used and retention times for 365 compounds were available. Compared to the results found with the established gas chromatography-mass spectrometry (GC-MS) procedure, the findings with the LC-QTOF-MS screening method showed a good comparability. Results that were not detected by LC-QTOF-MS because of a missing entry in the targeted XIC list could retrospectively be confirmed by simply entering the elemental formula of the relevant substance into the software and reprocessing the sample. LC-QTOF-MS offers an attractive technique for the fast and specific identification of illicit drugs and toxic compounds in urine samples. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27373550 TI - Diverse Ligand-Functionalized Mixed-Valent Hexamanganese Sandwiched Silicotungstates with Single-Molecule Magnet Behavior. AB - Under hydrothermal conditions, replacement of the water molecules in the [Mn(III) 4 Mn(II) 2 O4 (H2 O)4 ](8+) cluster of mixed-valent Mn6 sandwiched silicotungstate [(B-alpha-SiW9 O34 )2 Mn(III) 4 Mn(II) 2 O4 (H2 O)4 ](12-) (1 a) with organic N ligands led to the isolation of five organic-inorganic hybrid, Mn6 -substituted polyoxometalates (POMs) 2-6. They were all structurally characterized by IR spectroscopy, elemental analysis, thermogravimetric analysis, diffuse-reflectance spectroscopy, and powder and single-crystal X-ray diffraction. Compounds 2-6 represent the first series of mixed-valent {Mn(III) 4 Mn(II) 2 O4 (H2 O)4-n (L)n } sandwiched POMs covalently functionalized by organic ligands. The preparation of 1-6 not only indicates that the double-cubane {Mn(III) 4 Mn(II) 2 O4 (H2 O)4-n (L)n } clusters are very stable fragments in both conventional aqueous solution and hydrothermal systems and that organic functionalization of the [Mn(III) 4 Mn(II) 2 O4 (H2 O)4 ](8+) cluster by substitution reactions is feasible, but also demonstrates that hydrothermal environments can promote and facilitate the occurrence of this substitution reaction. This work confirms that hydrothermal synthesis is effective for making novel mixed-valent POMs substituted with transition-metal (TM) clusters by combining lacunary Keggin precursors with TM cations and tunable organic ligands. Furthermore, magnetic measurements reveal that 3 and 6 exhibit single-molecule magnet behavior. PMID- 27373548 TI - Biogenesis of a new type of extracellular vesicles in gastrointestinal stromal tumors: ultrastructural profiles of spheresomes. AB - Extracellular vesicles (EVs) have emerged as an intercellular communication mediator in cancer. They seem to be involved in tumor processes by means of transformation of surrounding cells previous to metastasis by transferring miRNAs and oncogenic proteins. It is known that EVs, depending on their source, can be exosomes or ectosomes. Although the first type constitutes a specific population formed from the endosomal system, via multivesicular bodies, the ectosome biogenesis is not yet well known. In this study, we report a new type of EVs which has been termed spheresomes. While exosomes come from multivesicular bodies and ectosomes from direct budding of plasma membrane, spheresomes present a new mechanism of shedding from a spherical membrane structure which we have named multivesicular spheres. These EVs are first described in gastrointestinal stromal tumor cells in the present study. But moreover, these new membrane spherical structures appear not only next to tumoral cells but also different distances from them. Since some other authors have evidenced oncogenic KIT-containing EVs, it is also suggested here that surrounding cells uptake of these first described EVs, GIST-derived spheresomes, could induce tumor invasiveness. That is why the prevention of signaling processes developed by these new EVs may represent an alternative approach for GIST treatment. PMID- 27373551 TI - Fetal Membrane Ultrastructure and Development in the Oviparous Milksnake Lampropeltis triangulum (Colubridae) with Reference to Function and Evolution in Snakes. AB - In eggs of oviparous reptiles, fetal membranes maintain developing embryos through the exchange of respiratory gases and provision of water and calcium. As part of a survey of reptilian fetal membranes, we used scanning electron microscopy to study fetal membrane morphology in the oviparous Pueblan milksnake, Lampropeltis triangulum campbelli. The chorioallantois initially is an avascular structure lined by enlarged chorionic and allantoic epithelia. Upon vascularization, the chorionic epithelium becomes greatly attenuated, enhancing the potential for gas exchange; the allantoic epithelium also flattens. The bilaminar omphalopleure of the yolk sac lacks blood vessels, but it becomes vascularized by allantoic capillaries and transformed into an omphalallantois. Upon regression of the isolated yolk mass, this membrane is converted to chorioallantois, equipping it for gas exchange. Allantoic fluid serves as a water reservoir, and we postulate that it facilitates water uptake by establishing an osmotic gradient. Early in development, epithelia of both the chorion and the omphalopleure show apical microvilli that greatly increase the cell surface area available for water uptake. However, these features are incompatible with gas exchange and are lost as oxygen needs take precedence. A comparison of the fetal membranes to those of other squamate species (both oviparous and viviparous) reveals characteristics that are probably ancestral for snakes, some of which are plesiomorphic for Squamata. The widespread phylogenetic distribution of these features reflects their utility as adaptations that serve functional requirements of squamate embryos. PMID- 27373552 TI - Safety of peritoneal and pleural drain placement in pediatric stem cell transplant recipients with severe veno-occlusive disease. AB - Hepatic VOD (veno-occlusive disease) is a serious complication of HSCT (hematopoietic stem cell transplantation) and has historically been associated with high mortality. This obstruction to hepatic flow often results in fluid collections in the peritoneal and pleural cavities. Catheter placement to drain ascites or pleural fluid may reduce intra-abdominal hypertension and/or improve respiratory parameters. The safety of these interventions among critically ill, immunocompromised children is unknown. Among 32 HSCT recipients (2000-2012) with severe VOD, we assessed the primary outcome of procedural complication from peritoneal drain placement. Twenty-four (75%) patients underwent peritoneal drain placement. No patient sustained visceral perforation or hemorrhage with drain placement. Overall mortality was 47% (n = 15). The procedure was not associated with increased overall mortality (p > 0.99). Eight (25%) peritoneal drains required replacement for malfunction. Of 24 patients with peritoneal drains, one (4%) patient had a positive culture from ascitic fluid. Eight (25%) patients underwent pleural drain placement. No pleural drain-related procedural complication or infection occurred. Four (50%) of the eight patients with pleural drains had de-escalation in oxygen requirement at drain removal, compared to time of placement. In this study, peritoneal and pleural drains were safe interventions for children with severe VOD. PMID- 27373553 TI - Drug-specific CD4+ T-cell immune responses are responsible for antituberculosis drug-induced maculopapular exanthema and drug reaction with eosinophilia and systemic symptoms syndrome. AB - BACKGROUND: A multidrug regimen including isoniazid, rifampicin, pyrazinamide and ethambutol is commonly used as first-line treatment for tuberculosis. However, this regimen can occasionally result in severe adverse drug reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and drug induced liver injury. The culprit drug and mechanistic basis for the hypersensitive reaction are unknown. OBJECTIVES: To investigate drug-specific T cell responses in patients with antituberculosis drug (ATD)-induced cutaneous hypersensitivity and its underlying mechanism. METHODS: We enrolled eight patients with ATD-induced maculopapular exanthema and DRESS and performed a lymphocyte transformation test. Subsequently, drug-specific T-cell clones were generated from four of the patients who showed proliferation in response to ATDs. We measured the drug-specific proliferative responses and counted the drug specific interferon (IFN)-gamma/granzyme B-producing cells after drug stimulation. Antihuman leukocyte antigen (HLA) class I and class II blocking antibodies were used to analyse human leukocyte antigen-restricted T-cell responses. RESULTS: Positive proliferative responses to ATDs were mostly found in patients with cutaneous hypersensitivity. Furthermore, we isolated isoniazid/rifampicin-specific T cells from patients, which consisted primarily of CD4+ T cells. Drug-specific CD4+ T cells proliferated and secreted IFN gamma/granzyme B when stimulated with isoniazid or rifampicin, respectively. Isoniazid-responsive T-cell clones did not proliferate in the presence of rifampicin and vice versa. Drug-specific T-cell responses were blocked in the presence of anti-HLA class II antibodies. CONCLUSIONS: This study identifies the presence of isoniazid/rifampicin-specific T cells in patients with ATD-induced maculopapular exanthema and DRESS. Furthermore, it highlights the important role of drug-specific T-cell immune responses in the pathogenesis of these reactions. PMID- 27373554 TI - Understanding behavioural clusters: Identifying differences between clusters of health behaviours on key constructs. AB - OBJECTIVE: To uncover the rationale underlying the perceived distinction between clusters of health behaviours by identifying cognitive constructs that differentiate among them, and creating a 'cognitive profile' for each behavioural cluster. Thus, different determinants and characteristics of health behaviours (e.g. 'perceived behavioural control', 'impact on health', 'effort', 'non-health rewards', 'habit') were used to compare health behaviour meta-clusters (physical and psychosocial) and clusters (e.g. nutrition behaviours, substance abuse, medical practices). METHODS: A sample of lay people (N = 1956) judged items representing behavioural clusters delineated in the Health Behaviour Taxonomy on 14 constructs. RESULTS: Significant differences emerged between the physical and psychosocial meta-clusters, as well as among their sub-clusters. For example, physical behaviours were higher on 'perceived behavioural control' and 'impact on health' compared to psychosocial behaviours, and nutrition was perceived highest on 'effort' and 'non-health rewards' compared to the other clusters of the physical meta-cluster. CONCLUSION: The findings increase our understanding of the logic underlying lay people's cognitive schema of health behaviour clusters. 'Cognitive profiles' that explain differences between the clusters were identified, which can be used to design health messages and interventions targeting multiple health behaviours. PMID- 27373555 TI - eNOS gene T786C, G894T and 4a4b polymorphisms and male infertility susceptibility: a meta-analysis. AB - : The association between polymorphism of eNOS and male infertility in several studies was controversial. To explore a more precise estimation of the association, a meta-analysis of eight case-control studies, including 1,968 cases and 1,539 controls, were selected. The meta-analysis was conducted by calculating the pooled odds ratio (OR) with a 95% confidence interval (95% CI). Overall, the association between T786C and risk of male infertility was obvious (TC vs. TT: OR, 1.20; 95% CI, 1.01-1.42; CC vs. TT: OR, 3.37; 95% CI, 1.65-6.87; TC/CC vs. TT: OR, 1.47; 95% CI, 1.25-1.73; CC vs. TT/TC: OR, 3.18; 95% CI, 1.54-6.56; TC vs. TT: OR, 1.65; 95% CI, 1.27-2.03). However, no overall association was observed between the other two polymorphisms of eNOS (G894T and 4a4b) and male infertility. Stratified analysis showed that significantly strong association between T786C polymorphism and semen quality was present in all three types of male infertility (azoospermia, oligozoospermia and asthenozoospermia). In the subgroup analysis based on ethnicity, both T786C and 4a4b could influence the risk of male infertility in Asian and Caucasian. Further studies of polymorphisms of eNOS with their biological functions are needed to understand the role in the development of male infertility. PMID- 27373557 TI - Miniaturized Linear Wire Ion Trap Mass Analyzer. AB - We report a linear ion trap (LIT) in which the electric field is formed by fine wires held under tension and accurately positioned using holes drilled in two end plates made of plastic. The coordinates of the hole positions were optimized in simulation. The stability diagram and mass spectra using boundary ejection were compared between simulation and experiment and good agreement was found. The mass spectra from experiments show peak widths (fwhm) in units of mass-to-charge of around 0.38 Th using a scan rate of 3830 Th/s. The limits of detection are 137 ppbv and 401 ppbv for benzene and toluene, respectively. Different sizes of the wire ion trap can be easily fabricated by drilling holes in scaled positions. Other distinguishing features, such as high ion and photon transmission, low capacitance, high tolerance to mechanical and assembly error, and low weight, are discussed. PMID- 27373556 TI - A Two-Year Treatment of Amnestic Mild Cognitive Impairment using a Compound Chinese Medicine: A Placebo Controlled Randomized Trial. AB - We aimed to investigate the long-term therapeutic effects of a compound Chinese medicine, the Bushen capsule, on cognition and brain connectivity in patients with amnestic mild cognitive impairment (aMCI). Thus, sixty aMCI participants were recruited to this 24-month study and were randomly divided into treatment (30 with a Bushen capsule) and placebo (30 with a placebo capsule) groups. Neuropsychological tests with MMSE and episodic memory as the primary outcomes and resting-state functional magnetic resonance imaging (fMRI) were analyzed before and after the treatment over 24 month period. In contrast to the placebo group, the drug group presented improved or stable general cognitive function, memory, language and executive function especially the primary outcomes MMSE and episodic memory with Bushen capsule treatment. FMRI results showed increased connectivity in the right precuneus and the global connectivity indexed with goodness of fit (GOF) of the default mode network (DMN) in the drug group and decreased GOF in the placebo group. More importantly, we found the GOF change was positively correlated with changes in MMSE and memory scores after 24 months in the drug group. Over 24 months, treatment with the compound Chinese medicine Bushen capsule can improve multiple domains of cognition and increase the functional local (right precuneus) and global connectivity within the DMN, which are associated with better performance. PMID- 27373558 TI - On-Chip Quantitative Measurement of Mechanical Stresses During Cell Migration with Emulsion Droplets. AB - The ability of immune cells to migrate within narrow and crowded spaces is a critical feature involved in various physiological processes from immune response to metastasis. Several in-vitro techniques have been developed so far to study the behaviour of migrating cells, the most recent being based on the fabrication of microchannels within which cells move. To address the question of the mechanical stress a cell is able to produce during the encounter of an obstacle while migrating, we developed a hybrid microchip made of parallel PDMS channels in which oil droplets are sparsely distributed and serve as deformable obstacles. We thus show that cells strongly deform droplets while passing them. Then, we show that the microdevice can be used to study the influence of drugs on migration at the population level. Finally, we describe a quantitative analysis method of the droplet deformation that allows measuring in real-time the mechanical stress exerted by a single cell. The method presented herein thus constitutes a powerful analytical tool for cell migration studies under confinement. PMID- 27373560 TI - New insights into the vibrational and optical signatures of trans-stilbene via integrated experimental and quantum mechanical approaches. AB - The structure, spectroscopic parameters and optical properties of stilbene have been investigated by a computational protocol including suitable treatment of anharmonic contributions together with new experimental results. A full reproduction of the 500-3500 cm(-1) IR spectrum has been possible using the VPT2 approach and new insights are provided in the 6000 cm(-1) region where typical signatures have been characterized as a set of overtones and combination bands. Vibrational contributions to electronic transitions have been taken into account to simulate the optical (absorption and emission) properties of stilbene. Spectra simulated by employing the state-of-the-art Adiabatic Hessian model coupled to global hybrid functionals are in remarkable agreement with their experimental counterparts and the inclusion of Herzberg-Teller contributions further improves the results with respect to those delivered by the basic Franck-Condon model. PMID- 27373559 TI - Detection of Novel Gene Variants Associated with Congenital Hypothyroidism in a Finnish Patient Cohort. AB - BACKGROUND: Congenital hypothyroidism (CH) is defined as the lack of thyroid hormones at birth. Mutations in at least 15 different genes have been associated with this disease. While up to 20% of CH cases are hereditary, the majority of cases are sporadic with unknown etiology. Apart from a monogenic pattern of inheritance, multigenic mechanisms have been suggested to play a role in CH. The genetics of CH has not been studied in Finland so far. Therefore, multigenic sequencing of CH candidate genes was performed in a Finnish patient cohort with both familial and sporadic CH. METHODS: A targeted next-generation sequencing (NGS) panel, covering all exons of the major CH genes, was applied for 15 patients with sporadic and 11 index cases with familial CH. RESULTS: Among the familial cases, six pathogenic mutations were found in the TPO, PAX8, and TSHR genes. Furthermore, pathogenic NKX2.1 and TG mutations were identified from sporadic cases, together with likely pathogenic variants in the TG, NKX2.5, SLC26A4, and DUOX2 genes. All identified novel pathogenic mutations were confirmed by Sanger-sequencing and characterized in silico and/or in vitro. CONCLUSION: In summary, the CH panel provides an efficient, cost-effective, and multigenic screening tool for both known and novel CH gene mutations. Hence, it may be a useful method to identify accurately the genetic etiology for dyshormogenic, familial, or syndromic forms of CH. PMID- 27373561 TI - In vitro monitoring of time and dose dependent cytotoxicity of aminated nanoparticles using Raman spectroscopy. AB - Investigation of possible adverse health effects of nanomaterials, in a rapid multi-parametric fashion, has become increasingly important, due to their increased production and potential uses in a wide range of application areas, from cosmetics to pharmaceutics. Although conventional in vitro cytotoxicological techniques provide valuable information about the particle toxicity, the importance of gaining high content information in a single assay with the analysis of multiple parameters in a non-invasive and label-free way is still one of the biggest challenges in nanotoxicology. As a vibrational spectroscopic technique, the power of Raman spectroscopy for the analysis of cells, tissues and also nanoparticle localization within cells has been shown previously. In this study, the ability of Raman spectroscopy to fingerprint the dose and time dependent cellular responses and effect of cytotoxic events on biochemical constituents of the cells is monitored. A549 human lung carcinoma cells and aminated polystyrene nanoparticles (PS-NH2) are used as a model cell line and nanoparticle, respectively. Following the determination of cellular responses in the presence of toxic PS-NH2 by using conventional cellular assays, Alamar Blue (AB) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT), and calculation of EC50 values for both assays, Raman spectroscopy was employed at response related doses and time points. Multiple point spectra from the cytoplasm, nucleus and nucleolus of 20 cells were acquired using Raman spectroscopy for each exposure dose and timepoint. Unsupervised principle components analysis (PCA) was applied to the Raman data sets for the comparison of exposed and unexposed cells as well as different exposure doses and times. The study shows the ability of Raman spectroscopy to provide information about cellular responses at different particle concentrations and exposure times with the aid of multivariate analysis. In the chosen range of concentrations, the most significant changes were observed in the cytoplasm for both time dependent and dose dependent cases due to the route of endocytosis. The Raman spectral markers for lipidosis, ROS formation and oxidative stress related biochemical damage are determined and correlated with exposure dose and time, and the responses are correlated with conventional cytotoxicity assays. PMID- 27373562 TI - Relativistic DFT and experimental studies of mono- and bis-actinyl complexes of an expanded Schiff-base polypyrrole macrocycle. AB - The computationally- and experimentally-determined molecular structures of a bis uranyl(vi) complex of an expanded Schiff-base polypyrrolic macrocycle [(UO2)2(L)] are in close agreement only if the pyridine in the fifth equatorial donor site on the uranium is included in the calculations. The relativistic density functional theory (DFT) calculations presented here are augmented from those on previously reported simpler frameworks, and demonstrate that other augmentations, such as the incorporation of condensed-phase media and the changes in the peripheral groups of the ligand, have only a slight effect. Synthetic routes to pure samples of the bis- and mono-uranyl(vi) complexes have been developed using pyridine and arene solvents, respectively, allowing the experimental determination of the molecular structures by X-ray single crystal diffraction; these agree well with the calculated structures. A comprehensive set of calculations has been performed on a series of actinyl AnO2n+ complexes of this macrocyclic ligand. These include both bis- and mono-actinyl adducts for the metals U, Np and Pu, and formal oxidation states VI and V. The reduction potentials of the complexes for U, Np, and Pu, incorporating both solvation and spin-orbit coupling considerations, show the order Np > Pu > U. The agreement between experimental and computed data for U is excellent, suggesting that at this level of computation predictions made about the significantly more radiotoxic Np and Pu molecules should be accurate. A particularly unusual structure of the mononuclear plutonyl(v) complex was predicted by quantum chemical calculations, in which a twist in the macrocycle allows one of the two endo-oxo groups to form a hydrogen bond to one pyrrole group of the opposite side of the macrocycle, in accordance with this member of the set containing the most Lewis basic oxo groups. PMID- 27373563 TI - UV gelation of single-component polyacrylates bearing dinitrobenzoate side groups. AB - Polyacrylates bearing dinitrobenzoate side groups undergo sol-gel-sol transformations in DMF or THF solutions regulated by alternating UV light and dark conditions. The formation and recombination of radical ionic species via photoinduced electron transfer may be responsible. PMID- 27373564 TI - Sub-nanometre mapping of the aquaporin-water interface using multifrequency atomic force microscopy. AB - Aquaporins are integral membrane proteins that regulate the transport of water and small molecules in and out of the cell. In eye lens tissue, circulation of water, ions and metabolites is ensured by a microcirculation system in which aquaporin-0 (AQP0) plays a central role. AQP0 allows water to flow beyond the diffusion limit through lens membranes. AQP0 naturally arranges in a square lattice. The malfunction of AQP0 is related to numerous diseases such as cataracts. Despite considerable research into its structure, function and dynamics, the interface between the protein and the surrounding liquid and the effect of the lattice arrangement on the behaviour of water at the interface with the membrane are still not fully understood. Here we use a multifrequency atomic force microscopy (AFM) approach to map both the liquid at the interface with AQP0 and the protein itself with sub-nanometer resolution. Imaging using the fundamental eigenmode of the AFM cantilever probes mainly the interfacial water at the surface of the membrane. The results highlight a well-defined region that surrounds AQP0 tetramers and where water exhibits a higher affinity for the protein. Imaging in the second eigenmode is dominated by the mechanical response of the protein and provides sub-molecular details of the protein surface and the sub-surface structure. The relationship between modes and harmonics is also examined. PMID- 27373566 TI - [Pay attention to the fine management of the diagnosis and treatment of glaucoma]. AB - During the clinical practice of glaucoma, the fine management is needed in patient's eye history taking, clinical material organization, the standardization, normalization, advantage complement of clinical examination and compliance evaluation of anti-glaucoma medication. The fine management of the glaucoma diagnosis and treatment will enable the greatest extent of visual protection.(Chin J Ophthalmol, 2016, 52: 401-403). PMID- 27373567 TI - [The role of choroidal thickness change in acute attack of primary angle closure glaucoma]. AB - The mechanism of acute attack of primary angle closure glaucoma is unclear. Several studies showed that choroidal thickness was thicker in acute attack eyes than in follow eyes and normal eyes. However, these results are not enough to support the point that choroidal thickness increase is the cause for acute attack of primary angle closure glaucoma. Narrow anterior chamber angle, shallow anterior chamber are risk factors for primary angle closure glaucoma. Dynamic changes of iris, cilliary body crystalline lens and choroid all have effect on the angle width. They could contribute to the acute attack of angle closure. Thus, the acute attack of primary angle closure glaucoma should be the results of interaction effect of multiple risk factors. (Chin J Ophthalmol, 2016, 52: 404 406). PMID- 27373565 TI - Genome-wide analysis of HIF-2alpha chromatin binding sites under normoxia in human bronchial epithelial cells (BEAS-2B) suggests its diverse functions. AB - Constitutive functional HIF-2alpha was recently identified in cancer and stem cell lines under normoxia. In this study, BEAS-2B, a bronchial epithelial cell line, was shown to constitutively express active HIF-2alpha under normoxia and exhibit markers of pluripotency including Oct-4, Nanog, and sphere formation. Oct 4 expression was reduced after knockdown of HIF-2alpha under normoxia. Global enrichment analysis of HIF-2alpha demonstrated the diverse functions of HIF 2alpha under normoxia. Bioinformatics analysis of the enriched loci revealed an enhancer role of HIF-2alpha binding sites, involvement of HIF-2alpha interacting proteins, and enriched de novo motifs which suggest the diverse role of HIF 2alpha in pseudohypoxia. The low ratio of the discovered loci overlapping with those revealed in cancer cell lines 786-O (16.1%) and MCF-7 (15.9%) under hypoxia indicated a prevailing non-canonical mechanism. Hypoxia had positive, marginal or adverse effects on the enrichment of the selected loci in ChIP-PCR assays. Deletion of the N-terminal activation domain (N-TAD) of HIF-2alpha disrupted the reporting activity of two of the loci annotated to ELN and ANKRD31. Hypoxia incurring abundance variation of HIF-2alpha may misrepresent the N-TAD functions as canonical hypoxia inducible features via C-TAD activation. Elucidation of the pseudohypoxia functions of constitutive HIF-2alpha is useful for resolving its role in malignancy and pluripotency. PMID- 27373568 TI - [Effectiveness of unilateral selective laser trabeculoplasty for primary open angle glaucoma]. AB - OBJECTIVE: To study the effectiveness of unilateral selective laser trabeculoplasty (SLT) on the both eyes of patients with primary open-angle glaucoma (POAG). METHODS: This was a self-controlled clinical study. Thirty-two patients of 32 eyes with OAG who used same anti-glaucoma medications for both eyes were included aat the Department of Ophthalmology Peking University third Hospital from February 2010 to April 2014. SLT was performed for the poorly controlled eye for each patient. Patients were examined before operation and 1 hour, 1 week, 1 month, 3 months and 6 months after operation. The intraocular pressure was examined after 1 hour of SLT. The rest time points were examined by visual acuity, intraocular pressure (IOP), slit lamp microscope, fundus ophthalmoscope and visual field. The paired t test (Bonferroni) was used to compare the IOP at each time point after SLT with the baseline IOP before SLT. Single factor analysis of variance was used to compare the percentage of IOP drop. Linear correlation analysis was used to analyze the amplitude of the decrease of IOP between treated eyes and untreated eyes at 6-month post operatively and analyze the IOP between preoperative eyes and 6-month post operative eyes. The magnitude of the decrease of IOP in patients with glaucoma medication and 6 months after surgery was analyzed. We also analyzed the types of antiglaucoma medications and IOP reductions range for 6 month after SLT. RESULTS: The preoperative mean IOP was (18.9+/-2.5) mmHg (1 mmHg=0.133 kPa) in the treated eye of patients with OAG. Mean IOP reduction for 1 week, 1, 3, and 6 months after SLT were (1.7+/-2.9) mmHg, (2.5+/-2.5) mmHg, (3.5+/-2.8) mmHg, (3.4+/-2.5) mmHg and the percentage of IOP reduction were (8+/-16) %, (13+/-13) % (18+/-14) %, (18+/-12) % respectively (compared with the baseline, P< 0.05) . With the success criteria of IOP reduction >=3.0 mmHg or >=20%, the success rate of SLT in the treated eye after 1 week, 1, 3, 6 months was 38%, 52%, 50% and 60% respectively. For the untreated fellow eyes, the preoperative mean IOP was (17.3+/-2.4) mmHg. Mean IOP reduction for 1 week, 1month, 3 month, and 6 month after SLT were (1.1+/ 2.0) mmHg, (1.0+/-2.7) mmHg, (2.6+/-2.2) mmHg and (2.5+/-2.2) mmHg respectively (compared with the baseline, P<0.05) . There was a positive correlation between preoperative IOP and IOP reduction either in the treated or in the untreated eyes at 6-month post-SLT (R=0.63, P<0.01; R=0.60, P<0.01) . There was a positive correlation in IOP reduction between treated eyes and untreated eyes at 6-month post-operative (R=0.66, P<0.01). All patients didn't need further treatment such as another laser treatment or surgery. Anti-glaucoma medications were remained unchanged after SLT. CONCLUSIONS: In poorly anti-glaucoma medication controlled Chinese POAG eyes with mean IOP about 18.0 mmHg, unilateral STL can reduce the IOP about 18% at 6-month post-operative for the treated eyes. There was also a continuous IOP reduction effects for the fellow eyes.(Chin J Ophthalmol, 2016, 52: 410-415). PMID- 27373569 TI - [Effect of suture canalization on the treatment of primary open-angle glaucoma: 3 years clinical observation]. AB - OBJECTIVE: To evaluate the safety and effectiveness of the Suture Canalization, which is a kind of Schlemm canal surgery, on the treatment of patients with primary open angle glaucoma (POAG). METHODS: Retrospective cases series study. Fifty-two patients (52 eyes) with POAG were recruited from October 2007 to July 2009 from Hospital of Optometry and Ophthalmology, Wenzhou Medical University. Twenty-six patients (26 eyes) were included in the study group, who were treated with the Suture Canalization surgery with trabeculectomy. Twenty-six patients (26 eyes) were included as the control group, who were treated with trabeculectomy only. Best correct visual acuity (BCVA), intraocular pressure (IOP), bleb morphology, postoperative treatment of medicine of anti-glaucoma and complications of surgery were recorded at 1 d, 1 week, 1, 3, 6, 12, 18, 24, 30 and 36 months after surgery. After testing the normality and homogeneity of variance of the data of the multiple sets of measurement data, the variance analysis was adopted, and the t test was used in the comparison of two groups. Counting data using chi-square test, the level of variables between the groups should be compared with the rank sum test. RESULTS: No significant difference was found in baseline data, as well as the changes of BCVA between the study group and control group at the last visit (chi(2)=3.06, P=0.08) . Complete and qualified success was achieved in 18 (69.2%) and 23 (88.5%) cases separately in study group, 16 (61.5%) and 22 (84.6%) cases separately in control group (chi(2)=0.17, P=0.69) . There was no significant difference between two groups. IOP was decreased post-operatively: from (32.4+/-9.3) mmHg(1 mmHg=0.133 kPa)to (16.9+/-3.5) mmHg at the last visit in study group and (31.3+/-10.0) mmHg to (15.5+/-4.6) mmHg at the last visit in control group. There were significant difference between last visit and preoperative IOP between two groups (study group: t=8.12, P<0.01; control group: t=7.20, P<0.01). No significant difference was found between two groups in the decreased amplitude of IOP with treatment at the last visit (t=0.23, P=0.63), as well as the postoperative IOP at the different visits (P>0.05). 65.4% of cases in the study group and 61.5% patients in control group formed functional blebs (diffuse type and microcapsule type) at the last visit. No significant difference between the IOP of patients with functional blebs (15.5+/-3.5) mmHg and those with non-functional blebs (16.0+/ 3.4) mmHg in study group at the last visit (t=-0.49, P=0.64). No serious complications during and after surgery were found in subjects of the both groups. No significant difference was present in medicine amounts at last visit between the two groups (t=2.93, P=0.09). CONCLUSIONS: Suture Canalization is a safe and effective surgical procedure to decrease intraocular pressure in patients with POAG, through Schlemm canal and external filtration. While it maybe not suitable to the patient with high pre-operative IOP.(Chin J OPhthalmol, 2016, 52: 416 421). PMID- 27373570 TI - [Analysis of morphologic changes of lamina cribrosa in primary open angle glaucoma using enhanced depth imaging optical coherence tomography]. AB - OBJECTIVE: To analyze the morphologic changes of the lamina cribrosa (LC) in primary open angle glaucoma (POAG) patients using enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS: This was a case-control study. Serial horizontal and vertical B-scans of the optic nerve head were obtained from one eye of 52 POAG patients and 50 age- and sex-matched healthy subjects by EDI-OCT. The number and location of focal LC defects as well as their relationship with retinal nerve fiber layer(RNFL) defects were investigated in glaucomatous eyes and compared with healthy controls. The LC thickness was measured at the center of mid-superior, central, and mid-inferior horizontal B-scans. The intra- and interobserver reproducibility were evaluated by intraclass correlation coefficient (ICC). A repeated measure ANOVA was used to analyze regional differences of the LC thickness. Independent t-test was conducted to compare LC thickness between POAG and healthy controls. A Pearson correlation was calculated for variation in LC thickness relative to global mean RNFL thickness. Spearman rank correlation was calculated to test the strength of the relationship between LC thickness and visual field mean deviation (MD). RESULTS: Twenty-six focal LC defects were found in 20 eyes (38.5%) with glaucoma versus none in the healthy controls. There were 13 (50.0%) focal LC defects in the inferotemporal sector, 6 (23.1%) defects in the inferior sector, 4 (15.4%) in the superotemporal sector, and 3 (11.5%) in the superior sector. Twenty-five of 26 focal LC defects (96.2%) corresponded to the RNFL defects. The intra- and interobserver ICCs of LC thickness measurement ranged from 0.90 to 0.95 and 0.84 to 0.90, respectively. The thicknesses of the superior midperipheral, central, and inferior midperipheral LC in POAG eyes were 180.7+/-26.3, 196.7+/-24.0, and 184.1+/-23.5 MUm, respectively. In healthy controls, the laminar thicknesses were 203.2+/ 21.0, 225.2+/-22.7, and 202.6+/-16.5 MUm, respectively. In both groups, the midperipheral LC was significantly thinner than the central LC (P<0.01). The mean LC thickness was (187.2+/-19.4) MUm in POAG eyes. It was significantly thinner than that in healthy controls (210.3+/-17.4 MUm) (t=5.06, P<0.01). The superior midperipheral, central, and inferior midperipheral regions of the LC were also significantly thinner in POAG than in controls (t=3.52 to 4.96, P<0.01). In POAG patients, mean LC thickness was found to significantly correlate with both global mean RNFL thickness (r=0.45, P<0.01) and visual field MD (rs=-0.58, P<0.01). CONCLUSIONS: The LC thickness was thinner in POAG than in healthy eyes, and correlated with the severity of POAG. Focal LC defects occurred frequently in POAG eyes, and might be associated with RNFL defect. EDI-OCT is a useful tool for the evaluation of LC deformation in glaucoma.(Chin J Ophthalmol, 2016, 52: 422 428). PMID- 27373571 TI - [Vision-and health-related quality of life in patients with uveitis]. AB - OBJECTIVE: To evaluate vision-and health-related quality of life in patients with uveitis, and to evaluate the relationship between quality of life and visual acuity. METHODS: Cross-sectional study. One hundred and eleven patients with uveitis were enrolled in the study from January 1, 2013 to April 1, 2014 in Peking University First Hospital. Clinical data collected included medical history, complete ophthalmologic examination and best corrected visual acuity (LogMAR). Basic clinical data (gender, diagnosis, etc.) was also collected. The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) and the 36 Item Short Form Health Survey (SF-36) were administered. The patients were divided into two groups, anterior uveitis group (ATU), and other types of uveitis in this study (OTU). T-test was used for analysis of the data which obey standard normal distribution, otherwise rank sum test was used for data analysis. Correlation and Linear regression were constructed between bilateral visual acuity and the scores of NEI VFQ-25 and SF-36 questionnaires. RESULTS: For all the 111 cases included in this study, 87 (78.4%) of them were anterior uveitis (ATU), 5 of them were intermediate uveitis, 7 of them were posterior uveitis and 12 of them were pan uveitis. Mean visual acuity of better and worse eye were 0.0 and 0.2 in ATU patients, respectively. Mean visual acuity of better and worse eye were 0.1 and 0.4 in OTU patients, respectively. Patients rated the general health subscale score of NEI VFQ-25 and SF-36 lower than other subscales, respectively (score of general health was 25.0 (25.0-50.0) in NEI VFQ-25 and 46.8 (19.8) in SF 36). ATU group scored higher that OTU group (Mean score of SF-36 was 77.5 (10.7) and 68.8 (16.9) in ATU and OTU group respectively, P value of SF-36< 0.01, t=9.54. Mean score of NEI VFQ-25 was 77.3 (12.8) and 59.1 (16.5) in ATU and OTU group respectively, P value of NEI VFQ-25<0.01, t=33.16). Mean score of NEI VFQ 25 of all patients was 73.4 (15.5). Mean visual acuity of better eye and worse eye of all patients were 0.0 (-0.2-1.0) and 0.3 (0.5), respectively. The correlation coefficient was -0.497 (P<0.01, t=-5.98) between NEI VFQ -25 score and visual acuity in better eye, and -0.32 (t=-3.48, P<0.01) between NEI VFQ-25 score and visual acuity in worse eye. The coefficient was -3.9 in linear regression of visual acuity in better eye against NEI VFQ-25 score (t=-5.98, P<0.01), and -1.1 of visual acuity in worse eye against NEI VFQ-25 score (t= 3.48,P<0.01). CONCLUSIONS: General health was more affected than other function subscales in uveitis. The quality of life in anterior uveitis was higher than other types of uveitis in this study. Vision-related quality of life correlated with both eyes.(Chin J Ophthalmol, 2016, 52: 429-436). PMID- 27373573 TI - [Protection of Verapamil against AGE induced apoptosis of human lens epithelial cell]. AB - OBJECTIVE: To investigate the protection of Verapamil against advanced glycation end products (AGE) induced human lens epithelial cells (HLEC) apoptosis. METHODS: Experiment study. SRA01/04 (HLEC line) was cultivated and passaged to the third generation and then divided into four groups. A group was named as control group, and B group was named as AGE group (LEC was treated by 20 MUmol/L AGE). C group was AGE+SB202190 group (LEC was treated 2 hours by SB2012190 and then treated by 15 MUmol/L AGE). D group was AGE+ Verapamil group (LEC was treated 2 hours by 50 MUmol/L Verapamil and then treated by AGE). MTT was used to evaluate the cell viability. Flow cytometry with Annexin V-FITC apoptosis detection was used to assess cell apoptosis.The expression of p-p38 and caspase3 was detected by Western blot between groups. One way Chi-square analysis was used for data analysis. LSD-t test was used as comparison between every two groups. RESULTS: After 24 hours, LEC viability (A570) was (0.28+/-0.08) in B group, which was significantly lower than A group (0.97+/-0.05) (LSD-t test, P=0.008). LEC viability in C and D group was (0.79+/-0.06) and (0.62+/-0.07) separately, which can partly higher than it was in B group (F=34.52, P=0.001). The apoptosis cells were (19.9+/-1.1)% in B group, which were significantly higher than they were in A group (2.5+/-0.6)% (P=0.003). The apoptosis cells in C and D group were (4.23+/ 1.20) and (5.79+/-1.75) separately, which were significant lower than they were in B group (F=371.61, P<0.01). In additional, expressions of p-p38, Caspase3 proteins in the cells of group B were (223.35+/-20.15) and (256.77+/-19.88) separately, which were higher than it were in A group,which were (106.44+/-10.74) and (100.26+/-18.65) separately. However, they were (139.17+/-19.10) and (142.75+/-23.36) in group C and (154.79+/-21.87) and (139.79+/-25.73) in group D (F=248.01, F=76.68; P<0.01), which were lower than they were in A group. CONCLUSION: p38 pathway is involved in the apoptotic procedure of LEC induced by AGE. Verapamil can interdict the p38 signal pathway and protect LEC apoptosis. (Chin J Ophthalmol, 2016, 52: 444-448). PMID- 27373572 TI - [Salubrinal protects human lens epithelial cells against endoplasmic reticulum stress-associated apoptosis]. AB - OBJECTIVE: To study the protective effect of Salubrinal on human lens epithelial cells and its mechanism in endoplasmic reticulum stress (ERS). METHODS: Hydrogen peroxide (H2O2 200 MUmol/L) was used to intervene in the cultured human lens epithelial cells B3 (HLE-B3) so as to create an oxidative stress model and induce ERS in the model. Different concentration of Salubrinal (10, 15, 20, 25, 30 and 35 MUmol/L) were added to the cultured HLE-B3 with or without H2O2 intervention. Then the cells were cultured for 24 hours. The cell counting kit (CCK-8) assay was used to test the viability of HLE-B3. The HLE-B3 cells were divided into three groups: Group A (normal control group), Group B (H2O2 200 MUmol/L group), and Group C (H2O2 200 MUmol/L+ Salubrinal 25 MUmol/L group). After 48 h, TUNEL and flow cytometry assay (FCM) were used to examine the effect of Salubrinal on HLE-B3 apoptosis. The expression of glucose-regulated protein 78(GRP78), C/EBP homologous protein (CHOP), cysteinyl aspartate specific proteinase 12 (Caspase 12) and phosphorylation eukaryotic translation initiation factor 2alpha (p elF2alpha) were tested by western blot at different points in time. Data from different groups was analyzed by one-way analysis of variance (ANOVA) while Dunnett t test was used under an equal condition, Dunnett's T3 for the unequal variances. RESULTS: CCK-8 results showed that without the intervention of H2O2, different concentrations of Salubrinal had no inhibitive effect on HLE-B3 viability, and that survival rates were (98.6+/-3.3) %, (98.7+/-2.6) %, (99.4+/ 3.2) %, (98.6+/-1.9) %, (98.8+/-2.5) %, (99.3+/-3.2) % and (99.5+/-2.4) %. There was no statistically significant difference between them (F=0.09, P=0.10). With the increasing of Salubrinal concentration, the survival rates of HLE-B3 in the presence of H2O2 intervention were (52.9+/-4.7) %, (65.0+/-3.6) %, (72.9+/-3.8) %, (84.5+/-3.6) %, (91.6+/-2.1) %, (93.1+/-2.9) %, (92.0+/-3.3) %. There was statistically significant difference from the control group (all P<0.01). However, the survival rates no longer increased (P=0.56, 0.88) if the Salubrinal concentration was greater than 25 MUmol/L. FCM results indicated that apoptosis rates of Group A, B and C were (1.9+/-0.7) %, (8.8+/-0.5) %, (4.3+/-0.3) %, respectively and the differences were statistically significant (F=396.26, P<0.01, comparing with Group A, all P<0.01). TUNEL results showed that apoptosis indexes of Group A, B, and C were (7.7+/-1.0) %, (36.9+/-1.0) %, (16.7+/-2.2) %, respectively and the differences were statistically significant. (F=618.39, P<0.01, comparing with Group A, all P<0.01). RESULTS of western blotting in group B at different points in time (0, 12, 24, 36, 48 h) showed that p-elF2alpha had increased by (2.16+/-0.38) times at 6 h; GRP78 had increased by (2.56+/-0.15) times at 12 h; CHOP started to rise after 12 h until it dropped after 24 h, and its amount had increased by (2.49+/-0.23) times at 48 h; Caspase-12 had increased significantly by (3.53+/-0.30) times at 48 h. The expression of GRP78, CHOP and p elF2alpha in group C was greater than that in Group B, but the expression of Caspase-12 in Group C was lower than that in Group B (GRP78: F=37.85, P<0.01; CHOP: F=61.09, P<0.01; Caspse-12: F=22.27, P<0.01; p-eIF2alpha: F=15.11, P<0.01). CONCLUSION: Salubrinal might protect HLE-B3 against H2O2-induced apoptosis by inhibiting ERS related apoptosis pathways.(Chin J Ophthalmol, 2016, 52: 437-443). PMID- 27373574 TI - [Microcirculation of optic nerve head and glaucoma]. AB - Glaucoma is a leading cause of irreversible blindness world widely. The pathogenesis of glaucoma is still not fully understood. It is proposed that the microcirculation of optic nerve head (ONH) may play an important role in glaucomatous optic neuropathy, but the hypothesis is still lack of direct evidence. In this review, we summarized the technical developments in ONH blood flow examination and findings on relationship between decreased ONH microcirculation and glaucoma. These evidences implicate that damaged ONH microcirculation involves in pathogenesis of glaucoma. (Chin J Ophthalmol, 2016, 52: 466-470). PMID- 27373575 TI - [Novel therapeutic targets for reduction of intraocular pressure in primary open angle glaucoma]. AB - Glaucoma is a major cause of blindness in China and the world. Currently, all therapeutic means in treating open-angle glaucoma are limited to control the progression of optic neuropathy by lowering intraocular pressure (IOP). Clinically available medicines lower IOP by either enhancing the uveoscleral pathway or inhibiting aqueous humor production. Since the primary cause of IOP elevation in POAG is elevated outflow resistance in the trabecular outflow pathway, current medicines are not able to correct the underlying pathogenesis and pathophysiology of the disease. In this review article, we discuss a series of new therapeutic targets and therapeutic approaches that are designed to directly modify the pathological changes related to the reduction in trabecular outflow in glaucoma patients. Some of these targets and approaches may produce a significant breakthrough in the treatment of this devastating disease. (Chin J Ophthalmol, 2016, 52: 471-475). PMID- 27373576 TI - [Role of microRNA in primary open-angle glaucoma]. AB - The pathogenesis of primary open-angle glaucoma (POAG) is still unclear. The trabecular meshwork (TM) plays an important role for regulation of aqueous humor outflow. The alteration of morphology, structure of TM cells and expression of extracellular matrix (ECM) components contribute to the abnormal increase of outflow resistance leading to elevated intraocular pressure (IOP). Recently, it has been confirmed that a variety of microRNA (miRNA) such as miRNA-29, 24, 200c and so on were expressed in TM tissue and different miRNA can affect the TM function and the synthesis of ECM in different ways. In this paper, we will review the role of miRNA in POAG pathogenesis, in order to provide the basis for probing into pathogenesis of glaucoma. (Chin J Ophthalmol, 2016, 52: 476-480). PMID- 27373577 TI - Corrigendum: Graphene Oxide promotes embryonic stem cell differentiation to haematopoietic lineage. PMID- 27373578 TI - 'Proyecto Orgullo', an HIV prevention, empowerment and community mobilisation intervention for gay men and transgender women in Callao/Lima, Peru. AB - We used qualitative, quantitative, and observational methods to assess the feasibility, acceptability, and potential efficacy of Proyecto Orgullo (PO), a pilot community mobilisation intervention to decrease sexual risk, promote health seeking behaviours, and facilitate personal and community empowerment among gay men (GM) and transgender women (TW) in Peru. PO was adapted from Mpowerment and Hermanos de Luna y Sol, two US interventions. PO included six interrelated core elements: (1) Self-reflection Small Group sessions; (2) Supporting peers in HIV prevention; (3) Mobilisation Activities addressing HIV, GM/TW issues, and community empowerment; (4) A Core Group (staff + GM/TW volunteers) designing/implementing those activities; (5) A Project Space; (6) Publicity. PO included specific components for TW, but promoted that GM/TW, who historically have not worked well together, collaborate for a common goal. We found that PO was embraced by GM/TW. PO positively influenced GM/TW's HIV prevention beliefs, self-efficacy, and behaviours; provided social support and created community; facilitated individual and community empowerment; achieved that GM/TW collaborate; and established a functional Community Centre for socialising/conducting mobilisation activities. Community mobilisation strategies, lacking from HIV prevention efforts in Peru but considered key to HIV prevention, can help improve health-seeking behaviours and consolidate social norms supporting preventive behaviours among GM/TW. PMID- 27373580 TI - Ulcerative colitis: A scientometric approach to the global research output and network. PMID- 27373579 TI - The determinants of defensive medicine in Italian hospitals: The impact of being a second victim. AB - BACKGROUND: Defensive medicine affects healthcare systems worldwide. The concerns and perception about medical liability could lead practitioners to practise defensive medicine. Second victim is a healthcare worker involved in an unanticipated adverse patient event. The role of being second victim and the other possible determinants for defensive medicine is mostly unclear. OBJECTIVE: To study the condition of being second victim as a possible determinants of defensive medicine among Italian hospital physicians. DESIGN, SETTING AND PARTICIPANTS: A secondary analysis of the database of the national survey study on the prevalence and the costs of defensive medicine in Italy that was carried out between April 2014 and June 2014 in 55 Italian hospitals was performed for this study. The demographic section of the questionnaire was selected including the physician's age, gender, specialty, activity volume, grade and the variable being a second victim after an adverse event. RESULTS: A total sample of 1313 physicians (87.5% response rate) was used in the data analyses. Characteristics of the participants included a mean age 49.2 of years and 19.4 average years of experience. The most prominent predictor for practising defensive medicine was the physicians' experience of being a second victim after an adverse event (OR=1.88; 95%CI, 1.38-2.57). Other determinants included age, years of experience, activity volume and risk of specialty. CONCLUSIONS: Malpractice reform, effective support to second victims in hospitals together with a systematic use of evidence-based clinical guidelines, emerged as possible recommendations for reducing defensive medicine. PMID- 27373581 TI - A PTSD symptoms trajectory mediates between exposure levels and emotional support in police responders to 9/11: a growth curve analysis. AB - BACKGROUND: Exposure to the terrorist attack on the World Trade Center (WTC) on 9/11/2001 resulted in continuing stress experience manifested as Posttraumatic Stress Disorder (PTSD) Symptoms in a minority of the police responders. The WTC Health Registry has followed up a large number of individuals, including police officers, at three waves of data collection from 2003 to 2011. This analysis examines the relationship between initial exposure levels, long-term PTSD symptoms, and subsequent emotional support among police responders. METHODS: The study population included police responders who had reported their 9/11 exposure levels at Wave 1 (2003/4), provided three waves of data on PTSD symptoms using the 17-item PCL scale, and rated their received emotional support at Wave 3 (N = 2,204, 1,908 men, 296 women, mean age: 38 years at exposure). A second-order growth curve reflected a PTSD symptom trajectory which was embedded in a structural equation model, with exposure level specified as an exogenous predictor, and emotional support specified as an endogenous outcome. RESULTS: Exposure had a main effect on mean symptom levels (intercept) across three waves but it made no difference in changes in symptoms (slope), and no difference in emotional support. The symptom trajectory, on the other hand, had an effect on emotional support. Its intercept and slope were both related to support, indicating that changes in symptoms affected later emotional support. CONCLUSIONS: Initial trauma exposure levels can have a long-term effect on mean symptom levels. Emotional support is lower in police responders when PTSD symptoms persist over seven years, but becomes higher when reduction in symptoms occurs. PMID- 27373582 TI - A comparative study between the implementation of the FRIDEX calibration and the NOGG guideline in the management of osteoporosis in routine clinical practice. AB - OBJECTIVE: The recent FRIDEX calibration proposed cost-effectiveness thresholds for the Spanish population. The aim of our study is to evaluate the impact of its application in routine clinical practice and to compare its thresholds with those of the National Osteoporosis Guideline Group (NOGG). MATERIAL AND METHODS: Cross sectional study in women referred to a bone densitometry unit who were not receiving antiresorptive therapy. The absolute risk of major fracture or hip fracture was calculated with the Spanish and British formulas of the FRAX(r) tool using the intervention thresholds of the FRIDEX calibration and the NOGG guideline, respectively. RESULTS: The study included 607 women with a median age of 59.4 (IQR=14) years. Treatment was initiated in 31.4% after bone mineral densitometry. With the application of the FRIDEX calibration, bone mineral density testing would have been indicated in 35.4% of the sample and treatment in 26.7%, reducing costs by 18.8% over a 5-year period. The NOGG guideline would have recommended testing in 32% and treatment in 21.3% of the participants, resulting in a reduction in costs of 35% over 5years, when compared with the standard approach. Agreement between the FRIDEX calibration and the NOGG guideline, as defined by Cohen's kappa coefficient, was low in terms of both diagnostic (0.16 [95%CI, 0.09-0.24]) and therapeutic indications (0.39 [95%CI, 0.31-0.47]). CONCLUSIONS: The application of the FRIDEX calibration and the NOGG guideline improves efficiency in the management of osteoporosis, although the level of agreement between the two is low. PMID- 27373583 TI - Profile of patients with fibromyalgia being treated in primary care centers in Terrassa, a city in northeastern Spain. AB - OBJECTIVE: To perform an extensive clinical and epidemiological characterization of our fibromyalgia patients. PATIENTS, MATERIAL, AND METHOD: Two-year observational study in 3 primary care centers in Terrassa, Spain. We recruited a sample of 235 individuals diagnosed with fibromyalgia being treated in primary care or rheumatology clinics who, when offered inclusion in a multidisciplinary program, agreed to provide the initial data we requested. The main measures were sociodemographic data, unhealthy habits and physical activity, comorbidities, treatment for fibromyalgia, Fibromyalgia Impact Questionnaire (FIQ), Hospital Anxiety and Depression Scale (HADS), and a family functioning scale (family APGAR). MAIN RESULTS: In all, 97.8% were women and the average age was 54.6 years. Most of the patients had a primary school education and the majority was on sick leave. Ninety-four percent had associated comorbidity and only 3% were not taking any medication for their disease. Many were taking drugs with no proven efficacy in fibromyalgia. The majority had intermediate scores on the FIQ, the HADS showed that 63% and 53% had an anxious and/or probable depressive disorder, respectively, and, according to the family APGAR score, 62% received proper family support. CONCLUSIONS: In agreement with the literature, the major findings in our fibromyalgia patients were a marked predominance of women, a high incidence of comorbidities-mainly psychiatric disorders-a moderate impact of the disease and widespread use of drugs with no demonstrated efficacy. PMID- 27373584 TI - Biological therapy and neurological manifestations. What do we know? AB - Biological therapy has changed the course of inflammatory rheumatic diseases. The safety is well documented in national and international studies. Neurological manifestations are uncommon and it is difficult to establish a clear causal relationship. The neurological signs and symptoms that may appear are multiple and sometimes mimic demyelinating neurological diseases and/or neurodegenerative diseases. Knowledge and disclosure of these cases is essential for a comprehensive management of biological therapy in our patients. PMID- 27373585 TI - Low-level laser therapy versus 5% amlexanox: a comparison of treatment effects in a cohort of minor aphthous ulcers patients-a commentary. PMID- 27373586 TI - Influence of anatomic position and intraoperative exposure of the inferior alveolar nerve on neurosensory disturbance after sagittal split ramus osteotomy: a three-dimensional computed tomography study. AB - OBJECTIVE: To evaluate the influence of the anatomic position and intraoperative exposure of the inferior alveolar nerve on neurosensory disturbance (NSD) in sagittal split ramus osteotomy. STUDY DESIGN: The anatomic factors of the nerve were measured on preoperative three-dimensional computed tomography in 98 patients. The intraoperative nerve exposure was assessed. NSD was evaluated for 1 year after surgery. The correlations between NSD and the factors were analyzed. RESULTS: The NSD decreased as the lateral marrow space from the nerve increased (P < .01). The complete nerve exposure increased NSD by 7.6 times (P = .01). The nerve exposure increased as the buccal plate thickness increased (P = .01) and decreased as the vertical marrow space from the nerve increased (P = .01). CONCLUSIONS: The nerve exposure and the lateral marrow space from the nerve affected NSD. The buccal plate thickness and the vertical marrow space indirectly affected NSD through nerve exposure. PMID- 27373587 TI - Alterations in Cardiac Mechanics Following Ultra-Endurance Exercise: Insights from Left and Right Ventricular Area-Deformation Loops. AB - BACKGROUND: The aim of this study was to use novel area-deformation (epsilon) loops to interrogate the interaction between the right ventricular (RV) and left ventricular (LV) mechanics following a 100-mile endurance run. METHODS: Fifteen participants (mean body mass, 70.1 +/- 8.8 kg; mean age, 40 +/- 8 years) were recruited for the study. Echocardiography was performed before the race, after the race, and 6 hours into recovery. RV and LV area and longitudinal epsilon were assessed using standard and speckle-tracking echocardiography. Following cubic spline interpolation, these variables were obtained across the same cardiac cycle and used to derive area-epsilon loops. RESULTS: The RV area-epsilon loop demonstrated a rightward shift after the race, with increased RV area (from 26.0 to 27.1 cm(2)) and reduced peak RV epsilon (from -28.6% to -25.8%). The recovery RV area-epsilon loop was similar to the postrace loop. A leftward shift was observed in the LV area-epsilon loop after the race, secondary to reduced LV area (from 35.8 to 32.5 cm(2)) and reduced peak epsilon (from -18.3% to -16.6%). In recovery, LV epsilon values returned toward baseline. CONCLUSIONS: A 100-mile ultramarathon resulted in a rightward shift in the RV area-epsilon loop as a result of RV dilatation. There was a concomitant leftward shift in the LV area epsilon loop as a result of underfilling of the left ventricle. At 6 hours after exercise, there was a partial recovery of the left ventricle, while RV function remained depressed. It appears that changes in RV function do not have a serial impact on the left ventricle during recovery from ultra-endurance activity. PMID- 27373588 TI - Dietary Advanced Glycation End Products and Risk of Chronic Kidney Disease. AB - OBJECTIVES: To evaluate the longitudinal association between dietary advanced glycation end products (AGEs) and risk of chronic kidney disease (CKD) in a population-based study. DESIGN AND SETTING: In a longitudinal design study, participants were evaluated after approximately 3 years. Daily consumption of carboxymethyl lysine, a major type of dietary AGEs, was determined using a validated semiquantitative food frequency questionnaire. Estimated glomerular filtration rate in this study was calculated by the Modification of Diet in Renal Disease formula. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2) based on the national kidney foundation guidelines. SUBJECTS: A total of 1,692 participants, free of baseline CKD with complete follow-up data, out of 3,462 subjects, age >=27 years of the third phase of Tehran Lipid and Glucose Study. MAIN OUTCOME MEASURES: The association between dietary AGEs and CKD was assessed using the multivariate logistic regression models. RESULTS: The mean age of participants was 43.4 +/- 11.4 years. The mean dietary intake of energy-adjusted AGEs was 8,336 +/- 1,532 kU/day. By increasing trend of AGE consumption, the percentage of fat intake increased (P < .001), whereas the percentage of carbohydrates and total fiber intake decreased (P < .001). Longitudinal analysis indicated that compared to the first quartile category of AGE intakes from fat, in participants of the fourth quartile category, the risk of CKD increased (odds ratio: 2.02; 95% confidence interval: 1.16-3.54). The odds of CKD had increasing trends across increasing categories of AGE intakes from fat (P for trend <.05). CONCLUSION: Higher consumption of AGEs through dietary fat was associated with higher risk of CKD incidence. PMID- 27373589 TI - Insulin influenced expression of myelin proteins in diabetic peripheral neuropathy. AB - Diabetic peripheral neuropathy (DPN) is one of the downstream complications of diabetes. This complication is caused by the deficiency of insulin action and subsequent hyperglycemia, but the details of their pathogenesis remain unclear. Hence, it is of critical importance to understand how such hormonal variation affects the expression of myelin proteins such as myelin basic protein (MBP) and myelin associated glycoprotein (MAG) in the peripheral nerve. An earlier report from our lab has demonstrated the expression of insulin receptors (IR) in Schwann cells (SCs) of sciatic nerve. To assess the neurotrophic role of insulin in diabetic neuropathy, we studied the expression of these myelin proteins under control, DPN and insulin treated DPN subjects at developmental stages. Further, the expression of these myelin proteins was correlated with the expression of insulin receptor. Expression of myelin proteins was significantly reduced in the diabetic model compared to normal, and upregulated in insulin treated diabetic rats. Similarly, an in vitro study was also carried out in SCs grown at high glucose and insulin treated conditions. The expression pattern of myelin proteins in SCs was comparable to that of in vivo samples. In addition, quantitative study of myelin genes by real time PCR has also showed the significant expression pattern change in the insulin treated and non-treated DPN subjects. Taken together, these results corroborate the critical importance of insulin as a neurotrophic factor in demyelinized neurons in diabetic neuropathy. PMID- 27373590 TI - Analysis of glucose metabolism of (18)F-FDG in major depression patients using PET imaging: Correlation of salivary cortisol and alpha-amylase. AB - Current diagnosis of Major depressive disorder (MDD) depends on its clinical symptoms, not on the results of any laboratory examinations. Establishing biological markers for diagnosis of MDD is one of the most important problems to be solved in psychiatry practice. MDD patients (n=8) and a healthy control group (n=8) were recruited in this study. Hamilton Depression Rating Scale (HAM-D) assessments were completed and saliva samples were collected for assessments of salivary cortisol and salivary alpha-amylase (sAA). PET examination was performed. Salivary cortisol and sAA in the MDD patients group were significantly higher than the healthy control group (P<0.001). MDD patients showed lower glucose metabolism of 18F-FDG in Cingulate Gyrus (BA24), Superior Frontal Gyrus (BA6), Rectal Gyrus (BA11) and Orbital Gyrus (BA11/47) compared with the healthy control group. The severity of depression, salivary cortisol and sAA correlated negatively with regional glucose metabolism in Cingulate Gyrus (BA 24), Superior Frontal Gyrus (BA 6), Rectal Gyrus (BA 11) and Orbital Gyrus (BA 11/47). The combination of salivary cortisol, sAA, superior frontal gyrus and rectal gyrus was the potential predictor of depression for MDD patients (DeltaR(2)=0.981, p<0.001). The present study showed that, MDD patients group showed higher salivary cortisol, sAA levels and lower glucose metabolism of (18)F-FDG in several brain areas compared with the healthy control group. The combination of salivary cortisol, sAA, glucose metabolism of (18)F-FDG of superior frontal gyrus and rectal gyrus may serve as a simple clinical tool for the early diagnosis of MDD. PMID- 27373591 TI - Effect of acute imipramine administration on the pattern of forced swim-induced c Fos expression in the mouse brain. AB - The forced swim test (FST) has been widely used for the preclinical evaluation of antidepressant drugs. Despite considerable differences in the protocol, equivalence of the FST for rats and mice has been rarely questioned. Previous research on the FST for rats revealed that repeated administration of antidepressant drugs attenuates the c-Fos response to swim stress in the hypothalamus and limbic regions. However, few studies have made similar investigations using the FST for mice. In the present study, we explored the mouse brain through immunohistochemistry staining for c-Fos after acute administration of imipramine or saline with or without a subsequent swim session. Imipramine enhanced the c-Fos density in regions of the central extended amygdala, while forced swim stress increased c-Fos expression in some hypothalamic (the ventrolateral preoptic nucleus and dorsomedial nucleus) and brain stem regions, which is consistent with previous reports. In contrast to previous literature with rats, swim stress brought a significant increase in c Fos expression in the lateral septal nucleus and some other regions in the hypothalamus (the intermediate hypothalamic area, the paraventricular and arcuate nucleus) only in the imipramine-pretreated group, which has not been observed previously. In the arcuate nucleus, double immunostaining revealed that c-Fos was rarely co-expressed with proopiomelanocortin or tyrosine hydroxylase regardless of imipramine treatment. The present results suggest that the activation of several regions in the lateral septum and the hypothalamus underlies antidepressant-like effect in the mouse FST. PMID- 27373592 TI - Light-melt adhesive based on dynamic carbon frameworks in a columnar liquid crystal phase. AB - Liquid crystal (LC) provides a suitable platform to exploit structural motions of molecules in a condensed phase. Amplification of the structural changes enables a variety of technologies not only in LC displays but also in other applications. Until very recently, however, a practical use of LCs for removable adhesives has not been explored, although a spontaneous disorganization of LC materials can be easily triggered by light-induced isomerization of photoactive components. The difficulty of such application derives from the requirements for simultaneous implementation of sufficient bonding strength and its rapid disappearance by photoirradiation. Here we report a dynamic molecular LC material that meets these requirements. Columnar-stacked V-shaped carbon frameworks display sufficient bonding strength even during heating conditions, while its bonding ability is immediately lost by a light-induced self-melting function. The light-melt adhesive is reusable and its fluorescence colour reversibly changes during the cycle, visualizing the bonding/nonbonding phases of the adhesive. PMID- 27373594 TI - [Serious concerns about multimodal treatments of cervical cancer]. PMID- 27373593 TI - A Combinatorial Algorithm for Microbial Consortia Synthetic Design. AB - Synthetic biology has boomed since the early 2000s when it started being shown that it was possible to efficiently synthetize compounds of interest in a much more rapid and effective way by using other organisms than those naturally producing them. However, to thus engineer a single organism, often a microbe, to optimise one or a collection of metabolic tasks may lead to difficulties when attempting to obtain a production system that is efficient, or to avoid toxic effects for the recruited microorganism. The idea of using instead a microbial consortium has thus started being developed in the last decade. This was motivated by the fact that such consortia may perform more complicated functions than could single populations and be more robust to environmental fluctuations. Success is however not always guaranteed. In particular, establishing which consortium is best for the production of a given compound or set thereof remains a great challenge. This is the problem we address in this paper. We thus introduce an initial model and a method that enable to propose a consortium to synthetically produce compounds that are either exogenous to it, or are endogenous but where interaction among the species in the consortium could improve the production line. PMID- 27373595 TI - Safety of DTaP-IPV/Hib vaccine administered routinely to infants and toddlers. AB - BACKGROUND: The combination DTaP-IPV/Hib vaccine was licensed in the United States in 2008 for children ages 6weeks through 4years with doses administered at 2, 4, 6, and 15-18months of age. The aim of this study was to assess the safety of DTaP-IPV/Hib vaccine routinely administered as part of clinical care to infants at Kaiser Permanente Northern California. METHODS: This was an observational, retrospective study that included all 2-month-old infants vaccinated with either DTaP-IPV/Hib or another DTaP-containing vaccine. We monitored all subjects for non-elective hospitalizations, emergency department visits and selected outpatient outcomes (seizures, Guillain-Barre Syndrome, encephalopathy, encephalitis, alteration of consciousness, meningitis, hypersensitivity reactions, immune thrombocytopenic purpura, hemolytic anemia, type 1 diabetes, and Kawasaki disease) beginning with their first dose through 6months after a 4th dose or until 24months of age. We calculated incidence rate ratios (IRRs) in the primary analysis by comparing rates of outcomes during the post-vaccination risk interval with rates during a comparison interval more remote from vaccination. Secondary analyses compared outcomes after DTaP-IPV/Hib with those after other DTaP-containing vaccines. We reviewed the medical records of selected outcomes. RESULTS: From October 1, 2008 through July 31, 2010, 14,042 subjects received a first dose of DTaP-IPV/Hib, 13,194 received 2 doses, 12,548 received 3 doses and 6702 received 4 doses. Overall, there were 166 comparisons with significantly elevated IRRs and 165 comparisons with significantly reduced IRRs. Medical record review of outcomes with significantly elevated IRRs in both the primary and secondary analyses did not suggest any relationship with DTaP IPV/Hib. CONCLUSIONS: This study did not detect any safety concerns following DTaP-IPV/Hib and provides reassurance that DTaP-IPV/Hib administered as part of routine care was not associated with unexpected safety risks. ClinicalTrials.gov Identifier: NCT00804284. PMID- 27373596 TI - Vesicular stomatitis virus-based vaccines expressing EV71 virus-like particles elicit strong immune responses and protect newborn mice from lethal challenges. AB - Enterovirus 71 (EV71) belonging to the Picornaviridae family is considered the most frequently detected causative agent in hand-foot-and-mouth disease (HFMD) and is a serious threat to public health in the Asia-Pacific region. There are currently no approved vaccines or effective drugs for EV71. In this study, using recombinant vesicular stomatitis virus (rVSV) expressing viral VP1 protein (mVP1) of EV71 as a control, we generated two types of rVSVs that can form EV71 virus like particles (VLPs). First, we co-infected two rVSVs singly expressing P1 (mP1) and 3CD (m3CD) of EV71. Second, we inserted P1 and 3CD into one VSV backbone to generate an rVSV expressing P1 and 3CD together (mP1-3CD). When P1 and 3CD were expressed in the cells either co-infected with mP1 and m3CD (mP1/m3CD) or infected with mP1-3CD, P1 was cleaved by 3CD and produced VP1, VP3, and VP0 to form VLPs. Furthermore, mice immunized with mP1/m3CD or mP1-3CD showed higher humoral and cellular immunity responses than mice immunized with mVP1. Finally, the rVSVs expressing the EV71 proteins were evaluated in mice to determine their potential to protect against a lethal EV71 virus challenge, and among all the rVSVs, the mP1-3CD was shown to be the most promising vaccine candidate for EV71 protection. PMID- 27373597 TI - Common genetic variants of GPC1 gene reduce risk of biliary atresia in a Chinese population. AB - BACKGROUND: Biliary atresia (BA) is a major neonatal cholestatic disease and main indication for pediatric liver transplantation in the world. Recently, GPC1 has been implicated as a risk gene for BA by genetic studies and follow-up functional experiments on zebrafish. METHODS: Two common genetic variants of GPC1, rs2292832 and rs3828336, were selected systematically through 'SNPinfo', and were examined using TaqMan Genotyping Assays for association studies in a Chinese population containing 134 cases and 618 controls. RESULTS: Of the two single nucleotide polymorphisms (SNPs), we found a significantly decreased BA risk associated with rs2292832 (additive model: OR=0.638, 95% CI: 0.467-0.873, P=0.005), and a marginal effect for rs3828336 (heterozygous model: OR=0.564, 95% CI: 0.312-1.020, P=0.058). The haplotype analysis indicated that either Crs2292832 Crs3828336&Trs3828336 or Trs2292832-Trs3828336 conferred a protective effect from BA (OR=0.569, 95% CI=0.414-0.783, P<0.001; OR=0.528, 95% CI: 0.301-0.926, P=0.026). Moreover, bioinformatics analysis suggested that rs2292832 altered GPC1 expression via effect on transcription-factor-binding sites (TFBS) of upstream binding transcription factor (UBTF), as a regulatory DNA variation in Deoxyribonuclease I (DNase I) hypersensitive sites (DHSs). CONCLUSION: Common variants of GPC1 gene were genetically involved in BA risk. PMID- 27373598 TI - The dirty side of the intrinsic pathway of coagulation. AB - Whereas the extrinsic pathway of coagulation seals off bleeding at the cut tissue edges, it is proposed that the intrinsic pathway exploits the dirt from the skin surface to generate an outer coagulum of the oozing blood. Activated Factor XII (FXIIa) in this outer cap generates Factor XIa, which triggers clotting, and kallikrein that feeds back to form more FXIIa to promote the process. This dirty wound hypothesis of coagulation function by the intrinsic pathway is supported by the use of dirt-based compounds in activated partial thromboplastin time assays as well as the evolutionary record where marine life that do not have skin adherent dirt lack Factor XII, including marine mammals that have returned to sea life. PMID- 27373599 TI - The role of screening, brief intervention, and referral to treatment in the perinatal period. AB - Substance use during pregnancy is at least as common as many of the medical conditions screened for and managed during pregnancy. While harmful and costly, it is often ignored or managed poorly. Screening, brief intervention, and referral to treatment is an evidence-based approach to manage substance use. In September 2012, the US Centers for Disease Control and Prevention convened an Expert Meeting on Perinatal Illicit Drug Abuse to help address key issues around drug use in pregnancy in the United States. This article reflects the formal conclusions of the expert panel that discussed the use of screening, brief intervention, and referral to treatment during pregnancy. Screening for substance use during pregnancy should be universal. It allows stratification of women into zones of risk given their pattern of use. Low-risk women should receive brief advice, those classified as moderate risk should receive a brief intervention, whereas those who are high risk need referral to specialty care. A brief intervention is a patient-centered form of counseling using the principles of motivational interviewing. Screening, brief intervention, and referral to treatment has the potential to reduce the burden of substance use in pregnancy and should be integrated into prenatal care. PMID- 27373600 TI - A method for sex estimation using the proximal femur. AB - The assessment of sex is crucial to the establishment of a biological profile of an unidentified skeletal individual. The best methods currently available for the sexual diagnosis of human skeletal remains generally rely on the presence of well preserved pelvic bones, which is not always the case. Postcranial elements, including the femur, have been used to accurately estimate sex in skeletal remains from forensic and bioarcheological settings. In this study, we present an approach to estimate sex using two measurements (femoral neck width [FNW] and femoral neck axis length [FNAL]) of the proximal femur. FNW and FNAL were obtained in a training sample (114 females and 138 males) from the Luis Lopes Collection (National History Museum of Lisbon). Logistic regression and the C4.5 algorithm were used to develop models to predict sex in unknown individuals. Proposed cross-validated models correctly predicted sex in 82.5-85.7% of the cases. The models were also evaluated in a test sample (96 females and 96 males) from the Coimbra Identified Skeletal Collection (University of Coimbra), resulting in a sex allocation accuracy of 80.1-86.2%. This study supports the relative value of the proximal femur to estimate sex in skeletal remains, especially when other exceedingly dimorphic skeletal elements are not accessible for analysis. PMID- 27373601 TI - Development of a novel immuno-PCR for detection of avian leukosis virus. AB - Avian leukosis virus (ALV) is an important pathogen for various neoplasms, including lymphoid, myeloid, and erythroid neoplasms, and it causes significant economic loss in the poultry industry. Several efficient methods for the detection of ALV have been reported. However, these previously developed approaches are based on either PCR or immunoassays. Here, we used a proximity ligation technique and combined PCR with the immunoassay to develop a novel immuno-PCR (Im-PCR) approach for the detection of ALV. Our data showed that the Im-PCR had high specificity and sensitivity to ALV. The Im-PCR method selectively reacted to ALV but not to the other avian viruses tested. The limit of detection of Im-PCR could reach 0.5 TCID50. Moreover, the results of Im-PCR were in agreement with results from commercial ELISA when the clinical cloaca samples were used for ALV detection. The present results demonstrate that the novel Im PCR method can be efficiently applied to detect ALV in a clinical setting. Our data also highlight that Im-PCR may have promising applications in the diagnosis of pathogens. PMID- 27373602 TI - Large scale production of a mammalian cell derived quadrivalent hepatitis C virus like particle vaccine. AB - A method for the large-scale production of a quadrivalent mammalian cell derived hepatitis C virus-like particles (HCV VLPs) is described. The HCV core E1 and E2 coding sequences of genotype 1a, 1b, 2a or 3a were co-expressed in Huh7 cell factories using a recombinant adenoviral expression system. The structural proteins self-assembled into VLPs that were purified from Huh7 cell lysates by iodixanol ultracentrifugation and Stirred cell ultrafiltration. Electron microscopy, revealed VLPs of the different genotypes that are morphologically similar. Our results show that it is possible to produce large quantities of individual HCV genotype VLPs with relative ease thus making this approach an alternative for the manufacture of a quadrivalent mammalian cell derived HCV VLP vaccine. PMID- 27373603 TI - Community-engaged strategies to promote hepatitis B testing and linkage to care in immigrants of Florida. AB - To improve early identification and linkage to treatment and preventive services for hepatitis B virus (HBV) in persons born in countries with intermediate or high (>2%) HBV prevalence, the University of Florida Center for HIV/AIDS Research, Education, and Services (UF CARES) employed community-engaged strategies to implement the Hepatitis B Awareness and Service Linkage (HBASL) program. In this brief report, we present a summary of program components, challenges, and successes. Faith and community-based networks were established to improve HBV testing and screening and to increase foreign born nationals (FBNs) access to HBV care. A total of 1516 FBNs were tested and screened for hepatitis B. The majority were females (50.4%), Asians (62.8%), non-Hispanic (87.2%), and they also received post-test counseling (54.8%). Noted program advantages included the development of community networks and outreach to a large population of FBNs. The major challenges were institutional delays, pressures related to meeting program deliverables, and diversity within FBNs populations. Community health workers in the United States can replicate this program in their respective communities and ensure success by maintaining a strong community presence, establishing partnerships and linkage processes, developing a sustainability plan, and ensuring the presence of dedicated program staff. PMID- 27373604 TI - Optimised method to estimate octanol water distribution coefficient (logD) in a high throughput format. AB - Lipophilicity is one of the molecular properties assessed in early drug discovery. Direct measurement of the octanol-water distribution coefficient (logD) requires an analytical method with a large dynamic range or multistep dilutions, as the analyte's concentrations span across several orders of magnitude. In addition, water/buffer and octanol phases which have very different polarity could lead to matrix effects and affect the LC-MS response, leading to erroneous logD values. Most compound libraries use DMSO stocks as it greatly reduces the sample requirement but the presence of DMSO has been shown to underestimate the lipophilicity of the analyte. The present work describes the development of an optimised shake flask logD method using deepwell 96 well plate that addresses the issues related to matrix effects, DMSO concentration and incubation conditions and is also amenable to high throughput. Our results indicate that the equilibrium can be achieved within 30min by flipping the plate on its side while even 0.5% of DMSO is not tolerated in the assay. This study uses the matched matrix concept to minimise the errors in analysing the two phases namely buffer and octanol in LC-MS. PMID- 27373605 TI - Pharmacokinetics and pharmacodynamics of two different landiolol formulations in a healthy Caucasian group. AB - BACKGROUND: To date, no data have been reported on the pharmacokinetic and pharmacodynamic properties of landiolol, a fast-acting cardioselective beta1 adrenergic antagonist, in non-Asian subjects. The aim of this study was to compare two landiolol formulations in healthy Caucasian subjects. MATERIALS AND METHODS: We conducted a single-center, prospective, double-blinded, randomized study in two cross-over periods with 12 healthy subjects (7 women and 5 men) each receiving three doses (0.1, 0.2, and 0.3mg/kg BW) of Onoact(r) 50 Lyophilized powder (50mg) or Rapibloc(r) concentrate IV (20mg/2mL) to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of the two landiolol formulations. RESULTS: For both formulations, maximum blood concentrations of landiolol were rapidly reached (median tmax 2.3+/-0.65 and 2.8+/-1.13min for the high dose of each formulation). The compounds had a short half-life (t1/2=3.2+/-1.2min and 3.0+/-1.1min for the low dose of the concentrate formulation and the lyophilized powder, respectively). The results showed no statistically significant differences between both formulations of landiolol for any PK parameters, at study doses. Both formulations dose-dependently and significantly decreased the heart rate values from 62.2bpm at baseline to minimum values of 55-56, 52-53, and 50-52bpm after 0.1, 0.2, and 0.3mg/kg respectively. This bradycardic effect was achieved within 1 to 3min. The decrease in systolic blood pressure (baseline: 107mmHg, minimum values were around 99mmHg) was significant but not dose dependent, and occurred within 3 to 12min. Seven mild to moderate AEs occurred after administration of the concentrate formulation. No SAEs were reported in this study. CONCLUSION: In Caucasians, both landiolol formulations showed similar pharmacokinetic behaviours, displaying very short half-lives (3.0 to 3.6min). In addition, after administration of both formulations, the landiolol-induced heart rate reduction showed fast onset and dose dependence, whilst the decrease of systolic blood pressure occurred more slowly, was less pronounced, and dose independent. In summary, both landiolol formulations delivered comparable plasma concentration profiles and showed good local tolerability. Overall, the pharmacokinetic and pharmacodynamic reactions observed in Caucasians were comparable to those described in Japanese subjects. PMID- 27373606 TI - Spectrum of Alcoholic Liver Disease. AB - Liver disease from excessive alcohol consumption is an important cause of morbidity and mortality worldwide. There is a clear relationship between alcohol and a variety of health and socioeconomic problems. According to the World Health Organization, 3.3 million people die of alcohol-related causes annually. Despite public knowledge of its potential adverse effects, alcohol consumption and the morbidity and mortality from alcoholic liver disease (ALD) have increased. ALD comprises a spectrum of injury, including simple steatosis, acute alcoholic hepatitis, and cirrhosis. Rather than being distinct disease entities, these pathologic processes frequently overlap. PMID- 27373607 TI - Unhealthy Alcohol Use. AB - Unhealthy alcohol use is common and routine screening is essential to identify patients and initiate appropriate treatment. At-risk or hazardous drinking is best managed with brief interventions, which can be performed by any provider and are designed to enhance patients' motivations and promote behavioral change. Alcohol withdrawal can be managed, preferably with benzodiazepines, using a symptom-triggered approach. Twelve-step programs and provider-driven behavioral therapies have robust data supporting their effectiveness and patients with alcohol use disorder should be referred for these services. Research now support the use of several FDA-approved medications that aid in promoting abstinence and reducing heavy drinking. PMID- 27373608 TI - Pathogenesis of Alcoholic Liver Disease. AB - Alcoholic liver disease includes a broad clinical-histological spectrum from simple steatosis, cirrhosis, acute alcoholic hepatitis with or without cirrhosis to hepatocellular carcinoma as a complication of cirrhosis. The pathogenesis of alcoholic liver disease can be conceptually divided into (1) ethanol-mediated liver injury, (2) inflammatory immune response to injury, (3) intestinal permeability and microbiome changes. Corticosteroids may improve outcomes, but this is controversial and probably only impacts short-term survival. New pathophysiology-based therapies are under study, including antibiotics, caspase inhibition, interleukin-22, anakinra, FXR agonist and others. These studies provide hope for better future outcomes for this difficult disease. PMID- 27373609 TI - Diagnosis of Alcoholic Liver Disease: Key Foundations and New Developments. AB - Alcoholic liver disease is a spectrum of conditions that include alcoholic fatty liver disease, alcoholic hepatitis, and chronic alcoholic liver disease. The diagnosis of alcoholic liver disease remains founded in an accurate patient history and detailed physical examination. Concurrent with the physical examination, objective data from laboratory, imaging, and histologic studies are helpful to confirm a diagnosis of alcoholic liver disease. Novel biomarkers, scoring systems, and imaging modalities are improving the ability to diagnose and manage alcoholic liver disease, but for most practicing clinicians, these have not been adopted widely because of their cost, but also because of limitations and uncertainty in their performance characteristics. PMID- 27373610 TI - The Pathology of Alcoholic Liver Disease. AB - The term "alcoholic liver disease" encompasses a spectrum of pathologic conditions ranging from isolated steatosis to established cirrhosis. Within this spectrum, varying degrees of inflammation, hepatocellular ballooning degeneration, hepatocyte necrosis, cholestasis, and fibrosis may be encountered. This article reviews the characteristic histologic features of the many forms of alcoholic liver disease. Histologic scoring systems are described, and diseases with overlapping morphologic features and comorbid conditions are also discussed. PMID- 27373611 TI - Prognosis and Prognostic Scoring Models for Alcoholic Liver Disease and Acute Alcoholic Hepatitis. AB - Multiple prognostic scoring systems have been developed to predict mortality from acute alcoholic hepatitis. Some systems, such as the modified discriminant function, are specific to alcoholic hepatitis. Others, such as the model for end stage liver disease, apply to a broad range of liver diseases. Prognostic factors are better at predicting patients who are likely to survive rather than die of this condition at 30 and 90 days. This important shortcoming may be improved by combining scores for better prediction accuracy. PMID- 27373612 TI - Acute Alcoholic Hepatitis, the Clinical Aspects. AB - Alcoholic hepatitis is an acute form of alcoholic liver disease with variable severity that develops in patients who usually have a history of prolonged and recent alcohol abuse. The diagnosis is clinical and depends on history, physical examination, and laboratory derangements. Liver biopsy is diagnostic but not universally performed, and noninvasive diagnostic modalities are under development. Scoring systems are used to assess severity of disease, predict mortality, and guide decisions for initiation of specific therapies. The natural history and long-term outcomes of alcoholic hepatitis, including recurrence, progression to cirrhosis, and mortality, vary and depend partly on abstinence from alcohol use. PMID- 27373613 TI - Acute Alcoholic Hepatitis: Therapy. AB - Alcoholic hepatitis (AH) causes great morbidity and mortality in the United States and throughout the world. Advances in therapy have proven difficult. In part, this reflects challenges in diagnosis, including the distinction between AH and acute-on-chronic liver failure. Liver biopsy is the best method to clarify the cause in circumstances whereby conflicting clinical data confound the diagnosis. All treatment of AH begins with abstinence from alcohol. All patients with AH should be given sufficient nutrition. Prednisolone has become the principal agent for treating patients with severe AH. PMID- 27373614 TI - Alcoholic Liver Disease and Liver Transplantation. AB - Excessive alcohol use is a common health care problem worldwide and is associated with significant morbidity and mortality. Alcoholic liver disease represents the second most frequent indication for liver transplantation in North America and Europe. The pretransplant evaluation of patients with alcoholic liver disease should aim at identifying those at high risk for posttransplant relapse of alcohol use disorder, as return to excessive drinking can be deleterious to graft and patient survival. Carefully selected patients with alcoholic liver disease, including those with severe alcoholic hepatitis, will have similar short-term and long-term outcomes when compared with other indications for liver transplantation. PMID- 27373616 TI - Long-Term Management of Alcoholic Liver Disease. AB - The key to management of alcoholic liver disease (ALD) is early recognition by the patient and physician. Excessive alcohol consumption, ranging from drinking more than recommended amounts to abuse, is one of the most preventable causes of death and disability. The US Preventive Services Task Force guidelines recommend screening for alcoholism in the primary care setting. Abstinence is the cornerstone of therapy and it decreases mortality and morbidity significantly. Alcoholic cirrhosis can cause varices that need to be followed closely with upper endoscopy to prevent or treat hemorrhage. In this review, we describe an approach to long-term management of ALD. PMID- 27373615 TI - Nutrition and Alcoholic Liver Disease: Effects of Alcoholism on Nutrition, Effects of Nutrition on Alcoholic Liver Disease, and Nutritional Therapies for Alcoholic Liver Disease. AB - Malnutrition is the most frequent and nearly universal consequence in alcoholic liver disease (ALD) that adversely affects clinical outcomes. Sarcopenia or skeletal muscle loss is the major component of malnutrition in liver disease. There are no effective therapies to prevent or reverse sarcopenia in ALD because the mechanisms are not well understood. Consequences of liver disease including hyperammonemia, hormonal perturbations, endotoxemia and cytokine abnormalities as well as the direct effects of alcohol and its metabolites contribute to sarcopenia in ALD. This article focuses on the prevalence, methods to quantify malnutrition, specifically sarcopenia and potential therapies including novel molecular targeted treatments. PMID- 27373617 TI - Alcoholic Liver Disease: High Risk or Low Risk for Developing Hepatocellular Carcinoma? AB - In this review we critically assess the literature to evaluate the level of risk posed by alcohol as both a primary etiology of hepatocellular carcinoma (HCC) and as a cofactor in its development. Although there have been conflicting findings, based on the body of evidence to date, it appears that the linkage between compensated alcoholic liver disease-associated cirrhosis and HCC is best characterized as medium-high risk, with the risk increasing with age and with quantity and duration of alcohol consumption and is more pronounced in females. While abstinence is the most effective way to reduce HCC risk, its effect seems largely dependent on the severity of liver damage at the point of cessation. Alcohol clearly interacts with other etiologies and conditions including viral hepatitis B and C, hereditary hemochromatosis, diabetes, and obesity to increase the risk for developing HCC, either synergistically or additively. Continued progress in genetics, especially through mechanistic-based and genome-wide association studies may ultimately identify which single nucleotide polymorphisms are risk factors for the onset of alcoholic liver disease and its progression to HCC and lead to the development of targeted therapeutics which may help providers better manage at-risk patients. PMID- 27373618 TI - The Effects of Alcohol on Other Chronic Liver Diseases. AB - Alcohol consumption is often a comorbid condition in other chronic liver diseases. It has been shown to act in synergy to increase liver injury in viral hepatitis, hereditary hemochromatosis, and nonalcoholic fatty liver disease (NAFLD), leading to an increased risk of cirrhosis, hepatocellular carcinoma, and liver-related mortality. Data suggest that modest alcohol consumption may be inversely related to the risk of developing NAFLD and lower rates of progression of NAFLD to nonalcoholic steatohepatitis (NASH). This article reviews data on the relationship between alcohol consumption and other chronic liver diseases. PMID- 27373620 TI - Alcoholic Liver Disease. PMID- 27373619 TI - Infection and Alcoholic Liver Disease. AB - Acute and chronic alcohol use leads to an impaired immune response and dysregulated inflammatory state that contributes to a markedly increased risk of infection. Via shared mechanisms of immune-mediated injury, alcohol can alter the clinical course of viral infections such as hepatitis B, hepatitis C, and human immunodeficiency virus. These effects are most evident in patients with alcoholic hepatitis and cirrhosis. This article provides an overview of alcohol's effect on the immune system and contribution to the risks and outcomes of specific infectious diseases. PMID- 27373621 TI - Foreword. PMID- 27373622 TI - pi-Delocalized Lipophilic Cations as New Candidates for Antimalarial, Antitrypanosomal and Antileishmanial Agents: Synthesis, Evaluation of Antiprotozoal Potency, and Insight into Their Action Mechanisms. AB - The search for new drugs that could treat tropical protozoan diseases, such as malaria or neglected tropical diseases (NTDs), motivates many medicinal chemists. New classes of antiprotozoal drugs that act through a novel mechanism of action must be developed. This review presents our efforts toward finding new candidate treatments for malaria, American trypanosomiasis, human African trypanosomiasis and leishmaniasis based on pi-delocalized lipophilic cations (DLCs). DLCs, such as rhodacyanines, azarhodacyanines, beta-carbolinium salts, and phenoxazinium salts, displayed strong antiprotozoal activities with highly selective indices. Several DLCs displayed moderate to excellent in vivo efficacies against Plasmodium berghei when administered intraperitoneally or orally. This review also discusses chemical biology approaches to understanding the mechanism of action underlying the antimalarial rhodacyanines. PMID- 27373623 TI - Mechanism of Creaming Down Based on Chemical Characterization of a Complex of Caffeine and Tea Catechins. AB - The component of a precipitate resulting from creaming down, which was made from caffeine and a catechin mixture, was determined by an integrated value of H2 proton signals of tea catechins in the quantitative (1)H-NMR spectrum. The results showed that gallate-type catechins formed a precipitate by creaming down more predominantly than non-gallate-type catechins. X-ray crystallographic analysis showed that the gallate-type catechin (-)-epigallocatechin-3-O-gallate (EGCg), (-)-epicatechin-3-O-gallate (ECg) formed 2 : 2 and 2 : 4 complexes with caffeine, respectively, and the non-gallate-type catechin (-)-epicatechin (EC) and caffeine formed a 1 : 1 complex. The 2 : 2, 2 : 4 complexes of caffeine and EGCg, ECg formed a hydrophobic space with three aromatic A, B, and B' rings of two EGCg, ECg molecules, and one caffeine molecule was captured in this hydrophobic space. However, no such hydrophobic space in the 1 : 1 complex of caffeine and EC formed. It was thought that the hydrophobicity of the 2 : 2, 2 : 4 complexes of caffeine and EGCg, ECg was stronger than that of the 1 : 1 complex of caffeine and EC, with the result that the 2 : 2, 2 : 4 complexes of caffeine and EGCg, ECg precipitated by creaming down more predominantly than the 1 : 1 complex of caffeine and EC in an aqueous solution. Furthermore, the molecular capture of various heterocyclic compounds by formation of the 2 : 2 complex of EGCg from the aqueous solution was investigated using the quantitative (1)H-NMR spectrum. PMID- 27373624 TI - Chemical Approaches to Elucidate Enzymatic Profiles of UDP-Glucose: Glycoprotein Glucosyltransferase. AB - In the endoplasmic reticulum (ER), uridine 5'-diphosphate-glucose: glycoprotein glucosyltransferase 1 (UGGT1) recognizes misfolded glycoproteins and transfers a glucose residue to the specific non-reducing end of high-mannose-type glycans. However, precise molecular mechanism by which UGGT1 senses the folding has not been understood clearly. To address this issue, various model substrates for UGGT1 have been prepared using biological approaches. Recently, we introduced chemical approaches using synthetic glycan probes that were designed for studying N-glycan processing in the ER and Golgi apparatus. Our approach can outfit the homogeneous and functionalized glycan probes. In this review, recent results on functional analysis of UGGT1 are summarized. PMID- 27373625 TI - Bromopyrrole Alkaloids from Okinawan Marine Sponges Agelas spp. AB - In our continuing study for structurally and biogenetically interesting natural products from marine organisms, Okinawan marine sponges Agelas spp. were investigated, resulting in the isolation of 18 unique alkaloids including five dimeric bromopyrrole alkaloids (1-5), ten monomeric bromopyrrole alkaloids (6 15), and three conjugates of monomeric bromopyrrole alkaloid and hydroxykynurenine (16-18). In this mini-review, the isolation, structure elucidation, and antimicrobial activities of these alkaloids are summarized. PMID- 27373626 TI - Chiral Integrated Catalysts Composed of Bifunctional Thiourea and Arylboronic Acid: Asymmetric Aza-Michael Addition of alpha,beta-Unsaturated Carboxylic Acids. AB - The first intermolecular asymmetric Michael addition of nitrogen-nucleophiles to alpha,beta-unsaturated carboxylic acids was achieved through a new type of arylboronic acid equipped with chiral aminothiourea. The use of BnONH2 as a nucleophile gives a range of enantioenriched beta-(benzyloxy)amino acid derivatives in good yields and with high enantioselectivity (up to 90% yield, 97% enantiomeric excess (ee)). The obtained products are efficiently converted to optically active beta-amino acid and 1,2-diamine derivatives. PMID- 27373627 TI - Beckmann Fragmentation and Successive Carbon-Carbon Bond Formation Using Grignard Reagents via Phosphonium Salt Intermediates. AB - The intermediates formed during the Beckmann fragmentation of alpha-alkoxy and alpha-alkoxy-alpha-alkyl oxime acetates have been successfully trapped as phosphonium salts, which were subsequently reacted with a variety of Grignard reagents to give the corresponding substituted products in good yields. Notably, this reaction proceeded smoothly even from alpha-alkoxy-alpha-alkyl oxime acetates. PMID- 27373628 TI - Isopetrosynol, a New Protein Tyrosine Phosphatase 1B Inhibitor, from the Marine Sponge Halichondria cf. panicea Collected at Iriomote Island. AB - A new polyacetylene compound, isopetrosynol (1), was isolated from the Okinawan marine sponge Halichondria cf. panicea together with petrosynol (2), adociacetylene D (3), (5R)-3,15,27-triacontatriene-1,29-diyn-5-ol (4), and petrosterol (5). The structure of 1 was assigned on the basis of spectroscopic data for 1 and 2. Compound 1 inhibited protein tyrosine phosphatase 1B (PTP1B) activity with an IC50 value of 8.2+/-0.3 uM, while compound 2, a diastereomer of 1, showed only 28.9+/-4.5% inhibition at 21.6 uM. The IC50 values of compounds 3 and 4 were 7.8+/-0.5 and 12.2+/-0.5 uM, respectively. Oleanolic acid, a positive control, inhibited PTP1B activity at 0.7+/-0.1 uM (IC50) in the same experiment. The inhibitory activity of 1 was stronger than that of its diastereomer (2). This is the first study to show the inhibitory effects of polyacetylene compounds on PTP1B. PMID- 27373629 TI - Enhanced Structural Variety of Nonplanar N-Oxyl Radical Catalysts and Their Application to the Aerobic Oxidation of Benzylic C-H Bonds. AB - The design and synthesis of structurally variable, nonplanar N-oxyl radical catalysts and their application to the aerobic oxidation, etherification, and acetoamidation of benzylic C-H bonds are described. The catalytic oxidation of C H bonds represents a powerful tool to synthesize oxygenated functional molecules from simple hydrocarbons in a straightforward way. Electron-deficient N-oxyl radical catalysts, such as phthalimidoyl N-oxyl (PINO) radical, generated from N hydroxyphthalimide (1), have attracted much attention because of their applications in the oxidation of C-H bonds with high bond dissociation energy (BDE). However, a few sites in 1 are available for structural modifications and improvements of the catalytic performance. By replacing one carbonyl group in 1 with a trifluoromethyl (CF3)-substituted sp(3)-carbon, we generated an additional tunable site and a nonplanar backbone, while retaining the desirable electron withdrawing properties and increasing the lipophilicity with respect to 1. We synthesized a variety of N-hydroxy precatalysts containing such a CF3 moiety, and investigated their utility in the aerobic oxidation of benzylic C-H bonds. Precatalysts with electron-withdrawing substituents, such as trifluoroethoxy and the acetophenone moieties, afforded higher yields than a corresponding methoxy substituted analogue. The introduction of substituents at the aromatic ring was also effective, as evident from the performance of 7-CF3 and 4,5,6,7-tetrafluoro precatalysts. Especially the combination of trifluoroethoxy- and 4,5,6,7 tetrafluoro substitution afforded a superior performance. These catalyst systems exhibited high functional group tolerance during the aerobic oxidation of C-H bonds, and benzylic etherification and Ritter-type reactions could be carried out at room temperature when a selected precatalyst and N-bromosuccinimide (NBS) were used. PMID- 27373630 TI - N-Methylniphatyne A, a New 3-Alkylpyridine Alkaloid as an Inhibitor of the Cancer Cells Adapted to Nutrient Starvation, from an Indonesian Marine Sponge of Xestospongia sp. AB - In the course of searching for selective growth inhibitors of the cancer cells adapted to nutrient starvation, a new 3-alkylpyridine alkaloid named N methylniphatyne A (1) was isolated from an Indonesian marine sponge of Xestospongia sp. The chemical structure of 1 was determined on the basis of the spectroscopic analysis and comparison with the synthesized 1 and its analogues. Compound 1 showed the cytotoxic activity against PANC-1 cells under the condition of glucose starvation with IC50 value of 16 uM, whereas no growth-inhibition was observed up to 100 uM under the general culture conditions. PMID- 27373631 TI - Enantioselective Total Synthesis of the Proposed Structure of Furan-Containing Polyketide. AB - Enantioselective total synthesis of the proposed structure of furan-containing polyketide was accomplished. The key features include a chemo- and enantioselective epoxidation of 1,4-cyclohexadiene by Shi asymmetric epoxidation, a regioselective epoxide ring opening, chemo- and diastereoselective dihydroxylation of the conjugated dienone derivative, and vinylation of the lactone accompanied by formation of the furan ring. PMID- 27373632 TI - Additional Nucleophile-Free FeCl3-Catalyzed Green Deprotection of 2,4 Dimethoxyphenylmethyl-Protected Alcohols and Carboxylic Acids. AB - The deprotection of the methoxyphenylmethyl (MPM) ether and ester derivatives can be generally achieved by the combinatorial use of a catalytic Lewis acid and stoichiometric nucleophile. The deprotections of 2,4-dimethoxyphenylmethyl (DMPM) protected alcohols and carboxylic acids were found to be effectively catalyzed by iron(III) chloride without any additional nucleophile to form the deprotected mother alcohols and carboxylic acids in excellent yields. Since the present deprotection proceeds via the self-assembling mechanism of the 2,4-DMPM protective group itself to give the hardly-soluble resorcinarene derivative as a precipitate, the rigorous purification process by silica-gel column chromatography was unnecessary and the sufficiently-pure alcohols and carboxylic acids were easily obtained in satisfactory yields after simple filtration. PMID- 27373634 TI - Conversion of Vindoline into 11-Mesyloxytabersonine. AB - Conversion of readily available vindoline to 11-mesyloxytabersonine, a versatile synthetic intermediate for indole alkaloids, has been achieved by a 9-step sequence in 39% overall yield. PMID- 27373633 TI - Synthesis and GGCT Inhibitory Activity of N-Glutaryl-L-alanine Analogues. AB - gamma-Glutamylcyclotransferase (GGCT) is an important enzyme that cleaves gamma glutamyl-amino acid in the gamma-glutamyl cycle to release 5-oxoproline and amino acid. Eighteen N-acyl-L-alanine analogues including eleven new compounds have been synthesized and examined for their inhibitory activity against recombinant human GGCT protein. Simple N-glutaryl-L-alanine was found to be the most potent inhibitor for GGCT. Other N-glutaryl-L-alanine analogues having methyl and dimethyl substituents at the 2-position were moderately effective, while N-(3R aminoglutary)-L-alanine, the substrate having an (R)-amino group at the 3 position or N-(N-methyl-3-azaglutaryl)-L-alanine, the substrate having an N methyl substituent on the 3-azaglutaryl carbon, in constract, exhibited excellent inhibition properties. PMID- 27373636 TI - Design, Synthesis and Biological Evaluation of a Structurally Simplified Syringolin A Analogues. AB - In this study, we designed and synthesized a structurally simplified syringolin A analogue 4, which could have a switched hydrogen bonding interaction with the beta5 subunit of 20S proteasome. This analogue exhibits potent beta5 proteasome inhibitory activity with an IC50 value of 107 nM. It also shows cytotoxicity against a range of human cancer cells at submicromolar level (109-254 nM). This analogue is expected to be a lead compound as a next generation proteasome inhibitor because of its simple structure. PMID- 27373635 TI - Construction of Azabicyclo[6.4.0]dodecatrienes Based on Rhodium(I)-Catalyzed Intramolecular [6+2] Cycloaddition between Azetidine, Allene, and Alkynes. AB - Treatment of the allenylazetidine-alkynes with a catalytic amount of [RhCl(CO)dppp]2 (dppp: 1,3-bis(diphenylphosphino)propane) effected the intramolecular hetero-[6+2]-type ring-closing reaction via the C-C bond cleavage of the azetidine ring to produce azabicyclo[6.4.0]dodecatriene derivatives in good to excellent yields. The formation of the oxa analogue could also be achieved. PMID- 27373637 TI - Peptide Nucleic Acid with a Lysine Side Chain at the beta-Position: Synthesis and Application for DNA Cleavage. AB - This paper reports the synthesis of new beta-Lys peptide nucleic acid (PNA) monomers and their incorporation into a 10-residue PNA sequence. PNA containing beta-Lys PNA units formed a stable hybrid duplex with DNA. However, incorporation of beta-Lys PNA units caused destabilization of PNA-DNA duplexes to some extent. Electrostatic attractions between beta-PNA and DNA could reduce this destabilization effect. Subsequently, bipyridine-conjugated beta-Lys PNA was prepared and exhibited sequence selective cleavage of DNA. Based on the structures of the cleavage products and molecular modeling, we reasoned that bipyridine moiety locates within the minor groove of the PNA-DNA duplexes. The lysine side chain of beta-PNA is a versatile handle for attaching various functional molecules. PMID- 27373638 TI - Convergent Synthesis of 2-Aryl-Substituted Quinolines by Gold-Catalyzed Cascade Reaction. AB - Gold-catalyzed auto-tandem catalysis has been developed for synthesizing 2-aryl substituted quinolines. The reaction of an aniline bearing an acetal moiety with an aryl alkyne proceeded via formal [4+2]-cycloaddition, which involved the addition of gold acetylide to an oxonium ion to give amino alkyne intermediate and sequential 6-endo-dig cyclization of amino alkyne intermediate by attacking of nitrogen to alkyne moiety activated by gold catalyst. The cationic gold catalyst promoted two different processes by enhancing the nucleophilicity and electrophilicity of alkyne. This convergent synthetic methodology enabled the synthesis of a variety of 2-aryl-substituted quinolines. PMID- 27373639 TI - Substituent Effect at the C4-Position of 1,3a,6a-Triazapentalene. AB - Various 2,4-disubstituted-1,3a,6a-triazapentalenes possessing methyl and phenyl groups at the C4-position were synthesized. Fluorescence observation of the synthetic 4-methyl- and 4-phenyl-1,3a,6a-triazapentalenes revealed that the introduction of a substituent at the C4-position allowed a long-wavelength shift of the fluorescence maximum. Furthermore, the phenyl group at the C4-position was found to induce a substantial increase in the extinction coefficient value. PMID- 27373640 TI - Glycosylation Reaction of Thioglycosides by Using Hypervalent Iodine(III) Reagent as an Excellent Promoter. AB - Thioglycosides are available donors in glycosylation due to the stability of the anomeric C-S bond under general reaction conditions of protection and deprotection, and offer orthogonality in their activation. We report now that the hypervalent iodine effectively induced glycosylation reaction of thioglycosides with various alcohols. This method features a high efficiency, completion in a short time, and proceeding under very mild conditions. PMID- 27373641 TI - Gold-Catalyzed Cyclization of Alkyne Alcohols: Regioselective Construction of Functionalized 6,6- and 6,7-Bicyclic Ethers. AB - We describe an efficient regioselective formation of six-/seven-membered cyclic ethers based on gold-catalyzed intramolecular hydroalkoxylation. Sequential gold catalyzed cyclization and palladium-catalyzed cross-coupling reactions afforded 6,6-bicyclic ethers, while reversing the reaction sequence (cross-coupling then cyclization) afforded 6,7-bicyclic ethers. This methodology should provide access to a range of functional polycyclic ethers. PMID- 27373642 TI - Synthesis and Antigenicity against Human Sera of a Biotin-Labeled Oligosaccharide Portion of a Glycosphingolipid from the Parasite Echinococcus multilocularis. AB - Synthesis of a biotinylated analog of the carbohydrate portion of a glycosphingolipid from the parasite Echinococcus multilocularis has been achieved. We synthesized beta-D-Galp-(1->6)-beta-D-Galp-(1->6)-[alpha-L-Fucp-(1 >3)]-beta-D-Galp-(1->R: biotin probe) (1) and compared the antigenicity by an enzyme linked immunosorbent assay (ELISA) with biotinylated trisaccharide alpha-D Galp-(1->4)-beta-D-Galp-(1->3)-alpha-D-Galp-(1->R: biotin probe) (F), which has been shown to have significant antigenicity. Both of the oligosaccharides reacted with sera of alveolar echinococcosis (AE) patients, but showed different reactivity. Among the 60 sera of AE patients, more sera reacted with the linear sequence Galalpha1->4Galbeta1->3GalNAcalpha1->R of oligosaccharide (F) than for branched compound 1. Some sera showed high specificity to one of the compound, indicating that the antibodies in the sera of AE patients differ in their specificity to recognize carbohydrate sequences of glycosphingolipids. Our results demonstrate that both of the biotinylated oligosaccharides 1 and F have good serodiagnostic potential and are complementary to detect infections caused by the parasite Echinococcus multilocularis. PMID- 27373643 TI - Aromatase Inhibitory Activity of Geranylated Coumarins, Mammeasins C and D, Isolated from the Flowers of Mammea siamensis. AB - A methanol extract of the flowers of Mammea siamensis (Calophyllaceae) was found to inhibit enzymatic activity against aromatase (IC50=16.5 ug/mL). From the extract, two new geranylated coumarins, mammeasins C (1) and D (2), were isolated together with seven coumarins: 8-hydroxy-5-methyl-7-(3,7-dimethyl-octa-2,6 dienyl)-9-(2-methyl-1-oxobutyl)-4,5-dihydropyrano[4,3,2-de]chromen-2-one (9), 8 hydroxy-5-methyl-7-(3,7-dimethyl-octa-2,6-dienyl)-9-(3-methyl-1-oxobutyl)-4,5 dihydropyrano[4,3,2-de]chromen-2-one (10), mammeas A/AA (14), A/AB (15), A/AA cyclo D (18), E/BA (23), and E/BC cyclo D (25). The structures of 1 and 2 were elucidated on the basis of spectroscopic evidence. Among the isolates including 17 previously reported coumarins, 1 (IC50=2.7 uM), 2 (3.6 uM), and mammea B/AB cyclo D (21, 3.1 uM) showed relatively strong inhibitory activities comparable to the activity of the synthetic nonsteroidal aromatase inhibitor aminoglutethimide (2.0 uM). PMID- 27373645 TI - Total Synthesis of Thailandepsin B, a Potent HDAC Inhibitor Isolated from a Microorganism. AB - Thailandepsin B, a bicyclic depsipeptide histone deacetylase inhibitor, was efficiently synthesized in 51% overall yield in eight steps, starting from commercially available D-norleucine methyl ester and known (S,E)-3-(4 methoxybenzyloxy)-7-(tritylthio)hept-4-enoic acid. The method features a convergent approach in which the corresponding seco-acid, a key precursor in macrolactonization, is directly assembled through the condensation of a D-allo isoleucine-D-cysteine-containing segment with a D-norleucine-containing segment. PMID- 27373644 TI - Structure-Activity Relationship Study of 3-Amino-2-indolyllactam Derivatives: Development of Inhibitors of Oxidative Stress-Induced Necrosis. AB - Modification of our previously reported selective inhibitor of oxidative stress induced necrosis, 2-(1H-indol-3-yl)-3-pentylamino-maleimide (IM-54) by regioselective reduction of the C-4 carbonyl group afforded a 3-amino-2 indolyllactam (IL-1) with more potent activity. To examine the structure-activity relationship of IL derivatives, we developed new synthetic routes with flexibility to incorporate a range of substituents at a late stage. The synthesized IL derivatives were evaluated for activity to inhibit necrotic cell death induced by hydrogen peroxide. Among them, IL-12 showed the most potent activity (IC50=49 nM) among the IL and indolylmaleimide (IM) derivatives examined. PMID- 27373646 TI - Theagalloflavic Acid, a New Pigment Derived from Hexahydroxydiphenoyl Group, and Lignan Oxidation Products Produced by Aerobic Microbial Fermentation of Green Tea. AB - Chinese ripe pu-erh tea is produced by aerobic microbial fermentation of green tea. To clarify the microbial degradation of tea polyphenols, Japanese commercial green tea was mixed with Chinese ripe pu-erh tea, which retains microorganisms, and fermented for 5 d. Chromatographic separation yielded a novel water-soluble yellow pigment termed theagalloflavic acid. Spectroscopic and chemical evidence suggested that this pigment was produced by oxidative ring cleavage of hexahydroxydiphenoyl esters. In addition, two new oxygenated lignin metabolites, (+)-5,5'-dihydroxypinoresinol and 5-hydroxydihydrodehydrodiconiferyl alcohol, were also isolated together with known degradation products of quercetin and tea catechins. PMID- 27373647 TI - Acylated Triterpene Saponins from the Stem Bark of Acer nikoense (Aceraceae). AB - Three new acylated triterpene saponins, acernikoenosides A-C (1-3), were isolated from the stem bark of Acer nikoense, together with a known sterol glucoside. Their structures were elucidated on the basis of extensive spectroscopic analyses. This study provided the first example of triterpene saponins isolated from this plant. The anti-genotoxic activity of 1, 3 and 4 against ultraviolet irradiation was evaluated by comet assay. PMID- 27373648 TI - Acceleration of Acid-Catalyzed Hydrolysis in a Biphasic System by Sodium Tetracyanocyclopentadienides. AB - The hydrolysis of tert-butyldimethylsilyl L-menthyl ether (3) in a CH2Cl2-1 M HCl biphasic solvent system was accelerated by the addition of sodium tetracyanocyclopentadienides 1. Particularly, the reaction rate was enhanced using sodium salt 1a-c with a lipophilic substituent on the cyclopentadienide ring. From the results obtained by a triphasic experiment, hydrolysis proceeds via the formation of hydronium ion 2 in the aqueous phase by ion exchange, followed by the transfer of 2 to the CH2Cl2 phase. PMID- 27373649 TI - Efficient N-Acyldopamine Synthesis. AB - N-Acyldopamines are endogenous analogs of capsaicin that exhibit cannabinoid-like activities and were identified from brain extracts. Among them, N arachidonoyldopamine (AADA) and N-oleoyldopamine (ODA) were characterized as transient receptor potential vanilloid type V1 channel (TRPV1) ligands. Recently, it was shown that N-acyldopamines may possess diverse physiological roles in addition to their ligand activities. To study the multiple functions and action mechanisms of endogenous N-acyldopamines, a simple and efficient method of N acyldopamine synthesis was investigated. The eighteen potentially endogenous N acyldopamines and two deuterated ones, N-palmitoyl dopamine-d5 and N-stearoyl dopamine-d5, were efficiently synthesized without protective groups in CH2Cl2 under optimized conditions using propylphosphoric acid cyclic anhydride (PPACA) as a condensation agent. PMID- 27373650 TI - Tandem Reaction of Enynyl Acetate: Precursor of Allenyl Ketones. AB - Deacetylation of enynyl acetates under basic conditions allows convenient access to reactive allenyl ketones, which can then undergo 1,4-addition of nucleophiles to furnish beta,gamma-unsaturated ketones. Benzofuran and indole derivatives have also been obtained from enynyl acetates with an o-hetero-atom-substituted aryl group via intramolecular 1,4-addition. PMID- 27373651 TI - Identification and Heterologous Expression of the Topopyrone Nonaketide Synthase Gene from Phoma sp. AB - Non-reducing iterative type I polyketide synthase genes, pnk1 and pnk2, were cloned from the fungus Phoma sp. BAUA2861, which produces the topoisomerase I inhibitors, topopyrones A to D. Heterologous expression of these polyketide synthase genes under the alpha-amylase promoter in Aspergillus oryzae was carried out to identify their functions. The pnk2 transformant produced topopyrones C, D, and haematommone. Therefore, the pnk2 gene was found to encode for the topopyrone nonaketide synthase. PMID- 27373652 TI - Metabolome Analysis of Oryza sativa (Rice) Using Liquid Chromatography-Mass Spectrometry for Characterizing Organ Specificity of Flavonoids with Anti inflammatory and Anti-oxidant Activity. AB - Oryza sativa L. (rice) is an important staple crop across the world. In the previous study, we identified 36 specialized (secondary) metabolites including 28 flavonoids. In the present study, a metabolome analysis using liquid chromatography-mass spectrometry was conducted on the leaf, bran, and brown and polished rice grains to better understand the distribution of these metabolites. Principal component analysis using the metabolome data clearly characterized the accumulation patterns of the metabolites. Flavonoids, e.g., tricin, tricin 7-O rutinoside, and tricin 7-O-beta-D-glucopyranoside, were mainly present in the leaf and bran but not in the polished grain. In addition, anti-inflammatory and anti-oxidant activity of the metabolites were assayed in vitro. Tricin 4'-O (erythro-beta-guaiacylglyceryl)ether and isoscoparin 2"-O-(6'''-(E)-feruloyl) glucopyranoside showed the strongest activity for inhibiting nitric oxide (NO) production and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging, respectively. PMID- 27373653 TI - Antimalarial Phenanthroindolizine Alkaloids from Ficus septica. AB - During the screening of antimalarial substances, MeOH extract from the twigs of Ficus septica was shown to have potent antimalarial activity. Bioassay-guided fractionation of a methanol extract of the twigs of F. septica led to the isolation of a new seco-phenanthroindolizine alkaloid and three known phenanthroindolizine alkaloids. Their structures were elucidated on the basis of NMR analysis. All isolated compounds were tested against Plasmodium falciparum. Compounds 2-4 displayed antimalarial activity against the 3D7 strain of P. falciparum with IC50 values 0.028-0.42 uM, whereas a new compound 1 exhibited a moderate antimalarial activity. PMID- 27373654 TI - Simple Synthesis of Sakuranetin and Selinone via a Common Intermediate, Utilizing Complementary Regioselectivity in the Deacetylation of Naringenin Triacetate. AB - Sakuranetin and selinone were successfully synthesized utilizing the regioselective deacetylation of naringenin triacetate. Deacetylation of the latter at C-7 with imidazole in 1,4-dioxane at 40 degrees C furnished the corresponding diacetate in 80% yield. Methylation of the obtained free hydroxy group and subsequent removal of the remaining two acetyl groups gave sakuranetin, which was previously isolated as a phytoalexin against rice blast disease fungus, Pyricularia oryzae, in 71% overall yield. The same intermediate, naringenin triacetate, was subjected to transesterification with 2-propanol in tetrahydrofuran, catalyzed by Candida antarctica lipase B. A contrasting regioselective preference for C-4' deacetylation was observed, giving an isomeric diacetate in 82% yield. Prenylation of the free hydroxy group under Mitsunobu conditions and subsequent deprotection furnished selinone, which was previously isolated from Monotes engleri and exhibits antifungal activity against Candida albicans, in 55% overall yield. PMID- 27373655 TI - Chemistry of Ecteinascidins. Part 5: An Additional Proof of Cytotoxicity Evaluation of Ecteinascidin 770 Derivatives. AB - Eleven 2'-N-acyl derivatives (5a-k) were prepared from ecteinascidin 770 (Et 770: 1b) via known 18,6'-O-bisallyl-protected compound (3) in three steps. Their in vitro cytotoxicities were determined by measuring IC50 values against human cell lines HCT116 and DU145. 5-Isoxazolecarboylamide derivative (5i) and 4 methoxybenzoylamide derivative (5k) were found to be promising leads for further optimization. PMID- 27373656 TI - Structures of Aromatic Glycosides from the Seeds of Cassia auriculata. AB - A new benzocoumarin glycoside, cassiaglycoside I (1), a new naphthol glycoside, cassiaglycoside II (2), a new chromon glycoside, cassiaglycoside III (3), a new phenylethyl glycoside, cassiaglycoside IV (4), were isolated from the seeds of Cassia auriculata, together with seven known constituents. The chemical structures of four new constituents were characterized on the basis of chemical and physicochemical evidence. PMID- 27373657 TI - Hyrtinadines C and D, New Azepinoindole-Type Alkaloids from a Marine Sponge Hyrtios sp. AB - New bisindole alkaloids, hyrtinadines C (1) and D (2), have been isolated from an Okinawan marine sponge Hyrtios sp. The structures of hyrtinadines C (1) and D (2) were elucidated based on analyses of the spectral data. Hyrtinadines C (1) and D (2) were the relatively rare alkaloids possessing a 3,4-fused azepinoindole skeleton. Hyrtinadines C (1) and D (2) showed antimicrobial activity. PMID- 27373658 TI - Biosynthetic Study of Amphidinin A and Amphidinolide P. AB - The biogenetic origins of amphidinin A (1) and amphidinolide P (2) were investigated by feeding experiments with (13)C-labeled acetates. (13)C-NMR data of (13)C-enriched samples revealed that the all carbons of 1 and 2 were derived from acetates. The polyketide chain of 1 was formed from one triketide chain, two diketide chains, and three unusual isolated C1 units derived from C-2 of cleaved acetates, while the polyketide chain of 2 was formed from one pentaketide chain, two acetate units, and three unusual isolated C1 units derived from C-2 of cleaved acetates. The all branched C1 units of 1 and 2 were derived from C-2 of cleaved acetates. PMID- 27373659 TI - Synthesis of Androprostamine A and Resormycin. AB - Syntheses of androprostamine A (1), and resormycin (3), anti-prostate cancer peptidyl natural products produced by microorganisms, were completed. The characteristic enamide structures of these compounds were installed using the Horner-Wadsworth-Emmons reaction from the corresponding phosphonates in reasonable Z-selectivity. PMID- 27373660 TI - In Vitro Antitrypanosomal Activity of the Secondary Metabolites from the Mutant Strain IU-3 of the Insect Pathogenic Fungus Ophiocordyceps coccidiicola NBRC 100683. AB - During the search for new antitrypanosomal drug leads, four antitrypanosomal compounds, of three depsipeptides and one nortriterpenoid, were isolated from cultures of the mutant strain IU-3 of the insect pathogenic fungus Ophiocordyceps coccidiicola NBRC 100683. Their structures were identified by the analysis of high resolution-electron ionization (HR-EI)-MS and HR-FAB-MS, and (1)H- and (13)C NMR spectra, including extensive two dimensional (2D)-heteronuclear NMR experiments, and comparison with literature data for destruxin A (1), destruxin B (2), destruxin E chlorohydrin (3) and helvolic acid (4). Compounds 1-4 showed in vitro antitrypanosomal activity against Trypanosoma brucei brucei GUTat3.1 with IC50 values of 0.33, 0.16, 0.061 and 5.08 ug/mL, respectively. PMID- 27373661 TI - Yezo'otogirins D-H, Acylphloroglucinols and Meroterpenes from Hypericum yezoense. AB - Investigation of the methanolic extract from the aerial parts of Hypericum yezoense resulted in the isolation of three new acylphloroglucinols, yezo'otogirins D-F (1-3), and two new meroterpenes, yezo'otogirins G (4) and H (5). The structures of 1-5 were assigned on the basis of spectroscopic data. Yezo'otogirin D (1) is an acylphloroglucinol with a monoterpene moiety linked through an ether bond, while yezo'otogirins E (2) and F (3) are polyprenylated acylphloroglucinols possessing a tricyclic core. Yezo'otogirins G (4) and H (5) are linear meroterpenes with an enolized beta-diketone moiety. Yezo'otogirin E (2) exhibited antimicrobial activity against Escherichia coli and Staphylococcus aureus. PMID- 27373662 TI - Novel 3,4,7-Substituted Benzofuran Derivatives Having Binding Affinity to kappa Opioid Receptor. AB - A series of novel 3,4,7-trisubstituted benzofuran derivatives were synthesized, and their binding affinity to kappa- (KOR) and MU-opioid receptors (MOR) were evaluated. Several aryl ethers showed moderate binding activities to KOR (IC50=3.9-11 uM) without binding to MOR. PMID- 27373663 TI - Functional Interrogation of the N-Terminal Lid of MDMX in p53 Binding via Native Chemical Ligation. AB - The homologous proteins MDM2 and MDMX negatively regulate the tumor suppressor protein p53 by antagonizing p53 transactivation activity and targeting p53 for degradation. MDM2 and MDMX bind to p53 via N-terminal p53-binding domains to control the level of p53. The N-terminal regions of MDM2 and MDMX are modified in vivo under stressed conditions, suggesting that modifications to MDM2/MDMX also may affect the p53-MDM2/MDMX interaction. Ample evidence suggests that the MDM2 lid (residues 1-24) is partially structured and significantly reduces its binding affinity with p53 several fold. Since MDM2 and MDMX possess very similar p53 binding domains but different lids, however, the function of the N-terminal lid of MDMX still remains poorly understood. Using a native chemical ligation technique, the p53-binding domain of MDMX, (1-108)MDMX, and its N-terminal lid (residues 1-23) truncated analogue (24-108)MDMX were chemically synthesized. We comparatively characterized their structures by circular dichroism (CD) spectra, and measured their binding affinities with a panel of p53-derived peptide ligands by fluorescence polarization and surface plasmon resonance assays. Our results indicate that, as opposed to the lid of MDM2, the lid of MDMX has little effect on p53-binding, adopts no structural conformation, and has rare auto-inhibitory function. Different lid modifications of MDM2 and MDMX are functionally different with respect to p53 binding, which should be considered when designing dual specific inhibitors of MDM2 and MDMX. PMID- 27373664 TI - O-Glycosylation of 4-(Substituted benzyl)-1,2-dihydro-3H-pyrazol-3-one Derivatives with 2,3,4,6-Tetra-O-acyl-alpha-D-glucopyranosyl Bromide via N1 Acetylation of the Pyrazole Ring. AB - A practical preparation of 4-(substituted benzyl)-3-(2,3,4,6-tetra-O-acyl-beta-D glucopyranosyloxy)-1H-pyrazole derivative 2 is described. O-Glycosylation of 4 (substituted benzyl)-1,2-dihydro-3H-pyrazol-3-one derivative 3 was facilitated by introduction of electron-withdrawing substituents, such as an acetyl group, at the N1-position of the pyrazole ring. 1-Acetyl-4-(substituted benzyl)-1,2-dihydro 3H-pyrazol-3-one 10 reacted with 2,3,4,6-tetra-O-acyl-alpha-D-glucopyranosyl bromide 5 in the presence of potassium carbonate in acetonitrile to provide the 1 acetyl-4-(substituted benzyl)-3-(2,3,4,6-tetra-O-acyl-beta-D-glucopyranosyloxy) 1H-pyrazole derivative 11 in high yield. When 2,3,4,6-tetra-O-pivaloyl-alpha-D glucopyranosyl bromide (5b) was used as a glycosyl donor, the resulting O glycosylated product 11 was N1-deacetylated in the presence of potassium bicarbonate in methanol without unfavorable deprotection of the glycosyl moiety to provide 2 in excellent yield. The synthetic intermediate 2b of Remogliflozin etabonate (1b) was synthesized using this strategy. PMID- 27373665 TI - Iriomoteolides-10a and 12a, Cytotoxic Macrolides from Marine Dinoflagellate Amphidinium Species. AB - Two new macrolides, iriomoteolides-10a (1) and -12a (2), have been isolated from a marine dinoflagellate Amphidinium sp. (KCA09053 strain), and their structures were elucidated on the basis of a detailed two dimensional (2D)-NMR analysis. Compound 1 is a novel 21-membered Amphidinium macrolide, which contains one tetrahydrofuran ring, two ketone carbonyls, two hydroxyl groups, and six one carbon branches. Compound 2 is a new 12-membered macrolide related to amphidinolide Q. Compound 1 exhibited cytotoxic activity against human cervix adenocarcinoma HeLa and murine hepatocellular carcinoma MH134 cells. PMID- 27373666 TI - Molecular Orbital Study of the Formation of Intramolecular Hydrogen Bonding of a Ligand Molecule in a Protein Aromatic Hydrophobic Pocket. AB - The natural product argadin is a cyclopentapeptide chitinase inhibitor that binds to chitinase B (ChiB) from the pathogenic bacteria Serratia marcescens. N(omega) Acetyl-L-arginine and L-aminoadipic acid of argadin form intramolecular ionic hydrogen bonds in the aromatic hydrophobic pocket of ChiB. We performed ab initio molecular orbital and density functional theory calculations to elucidate the role of this intramolecular hydrogen bonding on intermolecular interactions between argadin and ChiB. We found that argadin accrues large stabilization energies from the van der Waals dispersion interactions, such as CH-pi, pi-pi, and pi-lone pair interactions, in the aromatic hydrophobic pocket of ChiB, although intramolecular hydrogen bonding within argadin might result in loss of entropy. The intramolecular ionic hydrogen bonding formation canceled local molecular charges and provided good van der Waals interactions with surrounding aromatic residues. PMID- 27373667 TI - Reaction of 2a,8b-Dihydrobenzo[b]cyclobute[d]pyran-3-ones with Dimethylsulfoxonium Methylide. AB - Using dimethylsulfoxonium methylide as the methylene transfer reagent, 2a,8b dihydrobenzo[b]cyclobute[d]pyran-3-ones were converted into 2,2'-biphenol derivatives as major products and dihydrodibenzofurans as minor products. The reaction mechanism was extrapolated from a deuteration experiment with CD2=S(O)(CD3)2. PMID- 27373668 TI - Sesquiterpenoids from the Rhizomes of Curcuma phaeocaulis and Their Inhibitory Effects on LPS-Induced TLR4 Activation. AB - Two new guaiane-type (2, 6) and one new furanogermacrane-type (11) sesquiterpenoids have been isolated along with twelve known compounds from an EtOAc-soluble extract of Curcuma phaeocaulis rhizomes. The structures of the isolated compounds were elucidated using a combination of NMR, MS, and circular dichroism (CD) spectra. The inhibitory effects of each compound on lipopolysaccharide (LPS)-induced Toll-like receptor 4 (TLR4) activation in THP-1 Blue cells were assessed, and compound 4 showed more potent inhibitory activity against LPS-stimulated TLR4 activation. PMID- 27373669 TI - Synthesis of Dendrimers with a Bidentate Phosphine Core Ligand Having Carboxy Groups at the Peripheral Layer and Their Application to Aqueous Media Cross Coupling Reactions. AB - We prepared a series of dendrimers with a bidentate phosphine core ligand having carboxy groups at the peripheral layer. By employing the corresponding water soluble dendritic phosphine-palladium complex as a catalyst, the aqueous media Suzuki-Miyaura reaction and Tsuji-Trost reaction proceeded to provide the corresponding cross-coupling product. PMID- 27373671 TI - Radiofrequency ablation of symptomatic cervical inlet patch using a through-the scope device: a pilot study. AB - BACKGROUND AND AIMS: The cervical inlet patch (CIP) is an area of heterotopic gastric mucosa at the proximal esophagus, which can secrete both acid and mucus. Attributable symptoms include chronic globus sensation and sore throat. Previous studies have demonstrated improvement in symptoms after ablation using argon plasma coagulation. Our aim was to assess a through-the-scope radiofrequency ablation (RFA) catheter for ablation of symptomatic CIP. METHODS: Ten patients with endoscopically and histologically proven CIP and symptoms of globus or sore throat were included in the study. An ablation protocol of 3 ablations at 12 J/cm2, without removal of coagulated tissue between ablations, was used. A maximum of 2 RFA sessions, 3 months apart, was allowed. A visual analog score was completed at baseline, 6 weeks (on proton pump inhibitor), 3 months (off proton pump inhibitor), and 12 months after treatment. RESULTS: Mean patient age was 56 years (+/-3 years, standard error of the mean), 60% were men, and 80% were white. Barrett's esophagus was present in 50%. The mean number of CIPs was 2 (range, 1 4) with a median surface area of 2 cm2 (range, .5-14). After a median of 2 treatments, 80% achieved complete endoscopic and histologic resolution, with a mean follow-up of 14 months (range, 12-17). Globus, sore throat, and cough significantly improved from baseline (P < .05). No strictures or buried glands were identified. CONCLUSIONS: This prospective pilot study demonstrates that RFA using a through-the-scope device is safe and effective for treating patients with symptomatic CIP. One-year follow-up data suggest the effect is durable. PMID- 27373670 TI - Pharmacokinetic models of morphine and its metabolites in neonates:: Systematic comparisons of models from the literature, and development of a new meta-model. AB - Morphine is commonly used for pain management in preterm neonates. The aims of this study were to compare published models of neonatal pharmacokinetics of morphine and its metabolites with a new dataset, and to combine the characteristics of the best predictive models to design a meta-model for morphine and its metabolites in preterm neonates. Moreover, the concentration-analgesia relationship for morphine in this clinical setting was also investigated. A population of 30 preterm neonates (gestational age: 23-32weeks) received a loading dose of morphine (50-100MUg/kg), followed by a continuous infusion (5 10MUg/kg/h) until analgesia was no longer required. Pain was assessed using the Premature Infant Pain Profile. Five published population models were compared using numerical and graphical tests of goodness-of-fit and predictive performance. Population modelling was conducted using NONMEM(r) and the $PRIOR subroutine to describe the time-course of plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide, and the concentration analgesia relationship for morphine. No published model adequately described morphine concentrations in this new dataset. Previously published population pharmacokinetic models of morphine, morphine-3-glucuronide, and morphine-6 glucuronide were combined into a meta-model. The meta-model provided an adequate description of the time-course of morphine and the concentrations of its metabolites in preterm neonates. Allometric weight scaling was applied to all clearance and volume terms. Maturation of morphine clearance was described as a function of postmenstrual age, while maturation of metabolite elimination was described as a function of postnatal age. A clear relationship between morphine concentrations and pain score was not established. PMID- 27373672 TI - Adverse Outcomes in Relation to Polypharmacy in Robust and Frail Older Hospital Patients. AB - OBJECTIVE: To explore the relationship between polypharmacy and adverse outcomes among older hospital inpatients stratified according to their frailty status. DESIGN AND SETTING: A prospective study of 1418 patients, aged 70 and older, admitted to 11 hospitals across Australia. MEASUREMENTS: The interRAI Acute Care (AC) assessment tool was used for all data collection, including the derivation of a frailty index calculated using the deficit accumulation method. Polypharmacy was categorized into 3 groups based on the number of regular drugs prescribed. Recorded adverse health outcomes were falls, delirium, functional and cognitive decline, discharge to a higher level of care and in-hospital mortality. RESULTS: Patients had a mean (SD) age of 81 (6.8) years and 55% were women. Polypharmacy (5-9 drugs per day) was observed in 48.2% (n = 684) and hyper-polypharmacy (>=10 drugs) in 35.0% (n = 497). Severe cognitive impairment was significantly associated with nonpolypharmacy compared with polypharmacy and hyper-polypharmacy groups combined (P = .004). In total, 591 (42.5%) patients experienced at least 1 adverse outcome. The only adverse outcome associated with polypharmacy was delirium. Within each polypharmacy category, frailty was associated with adverse outcomes and the lowest overall incidence was among robust patients prescribed 10 or more drugs. CONCLUSION: While polypharmacy may be a useful signal for medication review, in this study it was not an independent predictor of adverse outcomes for older inpatients. Assessing the frailty status of patients better appraised risk. Extensive de-prescribing in all older inpatients may not be an intervention that directly improves outcomes. PMID- 27373674 TI - Aquaporin-4 deficiency facilitates fear memory extinction in the hippocampus through excessive activation of extrasynaptic GluN2B-containing NMDA receptors. AB - Aquaporin-4 (AQP-4) is the predominant water channel in the brain and primarily expressed in astrocytes. Astrocytes have been generally believed to play important roles in regulating synaptic plasticity and information processing. A growing number of evidence shows that AQP-4 plays a potential role in the regulation of astrocyte function. However, little is known about the function of AQP-4 for synaptic plasticity in the hippocampus. Therefore, we evaluated long term depression (LTD) in the hippocampus and the extinction of fear memory of AQP 4 knockout (KO) and wild-type (WT) mice. We found that AQP-4 deficiency facilitated fear memory extinction and NMDA receptors (NMDARs)-dependent LTD in the CA3-CA1 pathway. Furthermore, AQP-4 deficiency selectively increased GluN2B NMDAR-mediated excitatory postsynaptic currents (EPSCs). The excessive activation of extrasynaptic GluN2B-NMDAR contributed to the facilitation of NMDAR-dependent LTD and enhancement of fear memory extinction in AQP-4 KO mice. Thus, it appears that AQP-4 may be a potential target for intervention in fear memory extinction. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'. PMID- 27373673 TI - Synergy as a new and sensitive marker of basal ganglia dysfunction: A study of asymptomatic welders. AB - BACKGROUND: Multi-digit synergies, a recently developed, theory-based method to quantify stability of motor action, are shown to reflect basal ganglia dysfunction associated with parkinsonian syndromes. In this study, we tested the hypothesis that multi-digit synergies may capture early and subclinical basal ganglia dysfunction. We chose asymptomatic welders to test the hypothesis because the basal ganglia are known to be most susceptible to neurotoxicity caused by welding-related metal accumulation (such as manganese and iron). METHODS: Twenty right-handed welders and 13 matched controls were invited to perform single- and multi-finger pressing tasks using the fingers of the right or left hand. Unified Parkinson's Disease Rating Scale and Grooved Pegboard scores were used to gauge gross and fine motor dysfunction, respectively. High-resolution (3T) T1-weighted, T2-weighted, T1 mapping, susceptibility, and diffusion tensor MRIs were obtained to reflect manganese, iron accumulation, and microstructural changes in basal ganglia. The synergy index stabilizing total force and anticipatory synergy adjustments were computed, compared between groups, and correlated with estimates of basal ganglia manganese [the pallidal index, R1 (1/T1)], iron [R2* (1/T2*)], and microstructural changes [fractional anisotropy and mean diffusivity]. RESULTS: There were no significant differences in Unified Parkinson's Disease Rating Scale (total or motor subscale) or Grooved Pegboard test scores between welders and controls. The synergy index during steady-state accurate force production was decreased significantly in the left hand of welders compared to controls (p=0.004) but did not reach statistical significance in the right hand (p=0.16). Anticipatory synergy adjustments, however, were not significantly different between groups. Among welders, higher synergy indices in the left hand were associated significantly with higher fractional anisotropy values in the left globus pallidus (R=0.731, p<0.001) but not with the pallidal index, R1, or R2* values in the basal ganglia. CONCLUSIONS: These data suggest that multi-digit synergy metrics may serve as preclinical markers for basal ganglia dysfunction in welders and other populations at risk for neurodegenerative diseases involving parkinsonian symptoms. This finding may have important clinical, scientific, and public/occupational health implications. PMID- 27373675 TI - Activation of the FAK/PI3K pathway is crucial for AURKA-induced epithelial mesenchymal transition in laryngeal cancer. AB - Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors, and the main cause of death is metastasis. Overexpression of aurora kinase A (AURKA) plays an important role in the metastasis of LSCC. However, the mechanism by which AURKA promotes the metastasis of LSCC is poorly understood. Recent accumulating evidence indicates that epithelial-mesenchymal transition (EMT) may be one of the mechanisms of tumor metastasis. In the present study, we studied whether AURKA may induce EMT to promote the metastasis of LSCC. CCK-8 and plate colony-formation assays were carried out to show that AURKA significantly promoted the proliferation of Hep2 cells. Immunofluorescence staining and western blotting showed that EMT-related proteins changed in a time-dependent manner along with the alteration of AURKA, with decreased expression of N-cadherin, vimentin and slug and increased expression of E-cadherin. Additionally, downregulation of the expression of AURKA inhibited FAK/PI3K pathway activity. Inhibition of the FAK/PI3K pathway caused less mesenchymal-like characteristics and reduced the mobility, migration and invasion of Hep2 cells. In conclusion, AURKA may induce EMT to promote metastasis via activation of the FAK/PI3K pathway in LSCC. Those regulatory factors may present new diagnostic biomarkers and potential therapeutic targets for LSCC. PMID- 27373676 TI - A novel nonsense mutation in LMNA gene identified by Exome Sequencing in an atrial fibrillation family. AB - Genetic factor plays an important role in cardiac arrhythmias. Several loci have been identified associated with this disease. However, they only explained parts of it and more genes and loci remain to be identified. In present study, we recruited a four generation family from the north of China. Four members of this family were diagnosed with atrial fibrillation by electrocardiogram (ECG). We used Exome Sequencing and Sanger sequencing to explore the candidate mutation for cardiac arrhythmia in this family. A nonsense mutation (c.G1494A, p.Trp498Ter) in the LMNA gene were identified as the candidate mutation. This variant is a novel mutation and has not yet been reported for any actual databases. This novel mutation co-segregated exactly with the disease in this family. Meanwhile, it was not detected in 524 control subjects of matched ancestry. According to structural model prediction, the mutation is expected to affect the Lamin Tail Domain (LTD) of lamin A/C protein. So the nonsense mutation discovered in the family probably was a novel mutation associated with familial atrial fibrillation. This discovery expands the mutation spectrum of LMNA and indicates the importance of LMNA in AF. PMID- 27373677 TI - Socio-economic indicators are independently associated with intake of animal foods in French adults. AB - OBJECTIVE: The specific role of major socio-economic indicators (education, occupation, income) in influencing consumer choice of animal foods (AF) intake could reveal distinct socio-economic facets, thus enabling elucidation of mechanisms leading to social inequalities in health. We investigated the independent association of each indicator with intake of different AF and their effect modification. DESIGN: Cross-sectional study. AF intake was estimated using three 24 h dietary records. Associations between socio-economic factors and AF intake and interactions between socio-economic indicators were assessed using ANCOVA adjusted for age and energy intake. Analyses were performed separately for men and women, since gender interactions were found. SETTING: France. SUBJECTS: Adults (n 92 036) participating in the NutriNet-Sante Study. RESULTS: Low educated persons had higher intake of red meat (+9-12 g/d), processed meat (+6-9 g/d) and poultry (for men, +7 g/d) than those with a higher education level. Percentage of fish consumers was lower in individuals of the lowest income class compared with those in higher classes. Manual workers had a higher intake of cream desserts (for men, +14 g/d) than managerial staff. Few significant interactions were found. In stratified analyses, persons with the highest income consumed more yoghurt than those who had lower income, only in low educated individuals. CONCLUSIONS: Socio-economic disparities in AF intake varied according to the socio-economic indicator, suggesting the specific influence of each indicator on AF intake. In particular, lower education was associated with higher intake of red and processed meats and cream desserts, and had an effect modification on the relationship between income and AF intake. PMID- 27373678 TI - Histone methyltransferase Suv39h1 attenuates high glucose-induced fibronectin and p21(WAF1) in mesangial cells. AB - Suppressor of variegation 3-9 homolog 1 (Suv39h1) is a histone methyltransferase that trimethylates lysine 9 of histone H3 (H3K9me3), which results in gene silencing. A previous study found that H3K9me3 and Suv39h1 were decreased in diabetic mouse vascular smooth muscle cells whereas Suv39h1 overexpression attenuated ischemic myocardial injury. Moreover, high glucose (HG) decreased H3K9me3 and Suv39h1 levels in some cells. Thus, we studied the roles of Suv39h1 in HG-induced effects in MES13 (mouse mesangial) cells. We found that HG, chaetocin (a Suv39h1 inhibitor) and Suv39h1 siRNA decreased Suv39h1 while increasing fibronectin and p21(WAF1) protein levels. HG increased mRNA while chaetocin increased transcription of fibronectin and p21(WAF1)genes. Both HG and chaetocin decreased histone H3K9me3 levels at the promoters of fibronectin and p21(WAF1) genes. Additionally, Suv39h1 overexpression attenuated HG-induced fibronectin and p21(WAF1) mRNA and protein expressions while attenuating HG induced cell hypertrophy. Suv39h1 overexpression also attenuated HG-suppressed histone H3K9me3 levels at the promoters of fibronectin and p21(WAF1) genes. Moreover, LY294002 or the dominant-negative phosphoinositide 3-kinase (PI3K) mutant (Deltap85) attenuated HG-decreased Suv39h1 and HG-induced fibronectin and p21(WAF1) protein expressions. We concluded that HG decreased Suv39h1 via the PI3K pathway in mesangial cells. Inhibition of Suv39h1 increased fibronectin and p21(WAF1) expressions. Moreover, Suv39h1 overexpression attenuated HG-induced fibronectin and p21(WAF1) expressions and cell hypertrophy while attenuating HG suppressed histone H3K9me3 levels at the promoters of fibronectin and p21(WAF1) genes. PMID- 27373679 TI - Mitochondrial reactive oxygen species and inflammation: Molecular mechanisms, diseases and promising therapies. AB - Over the last few decades, many different groups have been engaged in studies of new roles for mitochondria, particularly the coupling of alterations in the redox pathway with the inflammatory responses involved in different diseases, including Alzheimer's disease, Parkinson's disease, atherosclerosis, cerebral cavernous malformations, cystic fibrosis and cancer. Mitochondrial dysfunction is important in these pathological conditions, suggesting a pivotal role for mitochondria in the coordination of pro-inflammatory signaling from the cytosol and signaling from other subcellular organelles. In this regard, mitochondrial reactive oxygen species are emerging as perfect liaisons that can trigger the assembly and successive activation of large caspase-1- activating complexes known as inflammasomes. This review offers a glimpse into the mechanisms by which inflammasomes are activated by mitochondrial mechanisms, including reactive oxygen species production and mitochondrial Ca2+ uptake, and the roles they can play in several inflammatory pathologies. PMID- 27373680 TI - Advanced glycation end products and their receptor in age-related, non communicable chronic inflammatory diseases; Overview of clinical evidence and potential contributions to disease. AB - Age-related, non-communicable chronic inflammatory diseases represent the major 21st century health problem. Especially in Western countries, the prevalence of non-communicable diseases like chronic obstructive pulmonary disease, cardiovascular disease, type 2 diabetes and osteoporosis are exponentially rising as the population ages. These diseases are determined by common risk factors and share an age-related onset. The affected organs display evidence of accelerated ageing, and are hallmarked by chronic inflammation and oxidative stress. The receptor for advanced glycation end products (RAGE) has been implicated in a number of inflammatory diseases and plays a central role in amplifying inflammatory responses. Advanced glycation end product (AGE) formation and accumulation is accelerated under these conditions. Advanced glycation end products are not only linked to RAGE signaling and inflammation, but to various hallmarks of the ageing process. In addition to these biological functions, circulating levels of the soluble form of RAGE and of advanced glycation end products are candidate biomarkers for many age-related inflammatory diseases. The purpose of this review is to provide an overview of the mechanistic connections between RAGE and advanced glycation end products and the processes of inflammation and ageing. Furthermore, through the presented overview of AGE-RAGE alterations that have been described in clinical studies in chronic obstructive pulmonary disease, cardiovascular disease, type 2 diabetes and osteoporosis, and insight obtained from mechanistic in vitro and animal studies, it can be concluded that these AGE-RAGE disturbances are a common contributing factor to the inflammatory state and pathogenesis of these various conditions. PMID- 27373681 TI - Tumor promoter PMA enhances kindlin-2 and decreases vimentin recruitment into cell adhesion sites. AB - Phorbol diester PMA (phorbol 12-myristate 13-acetate) is a well-known promoter of tumor progression. PMA also regulates cell adhesion by several mechanisms including conformational activation of integrins and integrin clustering. Here, PMA was shown to induce lamellipodia formation and reorganization of the adhesion sites as well as actin and vimentin filaments independently of integrin preactivation. To further analyze the mechanism of PMA action, the protein composition in the alpha1beta1 integrin/collagen IV adhesion sites was analyzed by mass spectrometry and proteomics. In four independent experiments we observed the reduced recruitment of vimentin in relation to integrin alpha1 subunit. This was in full agreement with the fact that we also detected the retraction of vimentin from cell adhesions by confocal microscopy. Furthermore, the accumulation of kindlin-2 into cell adhesions was significantly increased after PMA treatment. Kindlin-2 siRNA inhibited cell spreading as well as the formation of actin fibrils and cell adhesions, but did not prevent the effect of PMA on lamellipodia formation. Thus, kindlin-2 recruitment was considered to be a consequence rather than the primary cause for the loss of connection between vimentin and the adhesion sites. PMID- 27373682 TI - Inositol hexakisphosphate kinase-1 interacts with perilipin1 to modulate lipolysis. AB - Lipolysis leads to the breakdown of stored triglycerides (TAG) to release free fatty acids (FFA) and glycerol which is utilized by energy expenditure pathways to generate energy. Therefore, a decrease in lipolysis augments fat accumulation in adipocytes which promotes weight gain. Conversely, if lipolysis is not complemented by energy expenditure, it leads to FFA induced insulin resistance and type-2 diabetes. Thus, lipolysis is under stringent physiological regulation, although the precise mechanism of the regulation is not known. Deletion of inositol hexakisphosphate kinase-1 (IP6K1), the major inositol pyrophosphate biosynthetic enzyme, protects mice from high fat diet (HFD) induced obesity and insulin resistance. IP6K1-KO mice are lean due to enhanced energy expenditure. Therefore, IP6K1 is a target in obesity and type-2 diabetes. However, the mechanism/s by which IP6K1 regulates adipose tissue lipid metabolism is yet to be understood. Here, we demonstrate that IP6K1-KO mice display enhanced basal lipolysis. IP6K1 modulates lipolysis via its interaction with the lipolytic regulator protein perilipin1 (PLIN1). Furthermore, phosphorylation of IP6K1 at a PKC/PKA motif modulates its interaction with PLIN1 and lipolysis. Thus, IP6K1 is a novel regulator of PLIN1 mediated lipolysis. PMID- 27373683 TI - TFEB regulates PER3 expression via glucose-dependent effects on CLOCK/BMAL1. AB - It has been reported that metabolites regulate circadian rhythms through direct effects on clock genes. A metabolic network involving PER3 raises the possibility that some metabolic regulators are directly involved in the mammalian clock. Here, we show that the bHLH family transcription factor TFEB regulates PER3 through the CLOCK/BMAL1 complex. In the liver, TFEB expression displays circadian rhythms. A loss of TFEB function disrupts and dampens the expression of PER3 but not the expression of other circadian genes, such as PER1, PER2, CRY1 and CRY2. TFEB physically interacts with CLOCK/BMAL1 through its N-terminal region. In the presence of TFEB, BMAL1/CLOCK-mediated transcription is enhanced. Moreover, the TFEB/CLOCK/BMAL1 complex is regulated by glucose. These results show that TFEB has a role in the mammalian clock mechanism. PMID- 27373685 TI - Organization of the native ribosome-translocon complex at the mammalian endoplasmic reticulum membrane. AB - BACKGROUND: In eukaryotic cells, many proteins have to be transported across or inserted into the endoplasmic reticulum membrane during their biogenesis on the ribosome. This process is facilitated by the protein translocon, a highly dynamic multi-subunit membrane protein complex. SCOPE OF REVIEW: The aim of this review is to summarize the current structural knowledge about protein translocon components in mammals. MAJOR CONCLUSIONS: Various structural biology approaches have been used in synergy to characterize the translocon in recent years. X-ray crystallography and cryoelectron microscopy single particle analysis have yielded highly detailed insights into the structure and functional mechanism of the protein-conducting channel Sec61, which constitutes the functional core of the translocon. Cryoelectron tomography and subtomogram analysis have advanced our understanding of the overall structure, molecular organization and compositional heterogeneity of the translocon in a native membrane environment. Tomography densities at subnanometer resolution revealed an intricate network of interactions between the ribosome, Sec61 and accessory translocon components that assist in protein transport, membrane insertion and maturation. GENERAL SIGNIFICANCE: The protein translocon is a gateway for approximately one third of all synthesized proteins and numerous human diseases are associated with malfunctioning of its components. Thus, detailed insights into the structure and molecular organization of the translocon will not only advance our understanding of membrane protein biogenesis in general, but they can potentially pave the way for novel therapeutic approaches against human diseases. PMID- 27373684 TI - Alteramide B is a microtubule antagonist of inhibiting Candida albicans. AB - BACKGROUND: Alteramide B (ATB), isolated from Lysobacter enzymogenes C3, was a new polycyclic tetramate macrolactam (PTM). ATB exhibited potent inhibitory activity against several yeasts, particularly Candida albicans SC5314, but its antifungal mechanism is unknown. METHODS: The structure of ATB was established by extensive spectroscopic analyses, including high-resolution mass spectrometry, 1D and 2D-NMR, and CD spectra. Flow cytometry, fluorescence microscope, transmission electron microscope, molecular modeling, overexpression and site directed mutation studies were employed to delineate the anti-Candida molecular mechanism of ATB. RESULTS: ATB induced apoptosis in C. albicans through inducing reactive oxygen species (ROS) production by disrupting microtubules. Molecular dynamics studies revealed the binding patterns of ATB to the beta-tubulin subunit. Overexpression of the wild type and site-directed mutants of the beta tubulin gene (TUBB) changed the sensitivity of C. albicans to ATB, confirming the binding of ATB to beta-tubulin, and indicating that the binding sites are L215, L217, L273, L274 and R282. In vivo, ATB significantly improved the survival of the candidiasis mice and reduced fungal burden. CONCLUSION: The molecular mechanism underlying the ATB-induced apoptosis in C. albicans is through inhibiting tubulin polymerization that leads to cell cycle arrest at the G2/M phase. The identification of ATB and the study of its activity provide novel mechanistic insights into the mode of action of PTMs against the human pathogen. GENERAL SIGNIFICANCE: This study shows that ATB is a new microtubule inhibitor and a promising anti-Candida lead compound. The results also support beta-tubulin as a potential target for anti-Candida drug discovery. PMID- 27373687 TI - Chryseomicrobium palamuruense sp. nov., a haloalkalitolerant bacterium isolated from a sediment sample. AB - A novel Gram-stain-positive, rod shaped, motile bacterium, designated strain PU1T, was isolated from a sediment sample collected from a drainage near hostel of Palamuru University, Mahabubnagar district, T.S, India (16 degrees 43'23"N 77 degrees 58'49"E). Cells of strain PU1T are positive for catalase, oxidase, phosphatase, lipase and urease, and negative for gelatinase, amylase, protease, cellulase, lysine decarboxylase and ornithine decarboxylase. The fatty acids were dominated by saturated fatty acids (82.7 %), with a high abundance of iso-C15 : 0 (48.8 %), anteiso-C15 : 0 (7.3 %), iso-C16 : 0 (11.9 %), C16 : 1omega7c alcohol (11.8 %) and iso-C17 : 0 (5.3 %). Strain PU1T contained MK-8 as the major respiratory quinone and diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine make up the phospholipid composition. The cell-wall peptidoglycan contains meso-diaminopimelic acid as the diamino acid and cell-wall sugars are d-glucose and d-galactose. 16S rRNA gene sequence analysis indicated Chryseomicrobium imtechense and Chryseomicrobiumamylolyticum, members of family Planococcaceae within the phylum Firmicutes, are the closest related species with 16S rRNA gene sequence similarities of 99 %. Other members of the family Planococcaceae had sequence similarities of 99 %, and DNA-DNA relatedness values between strain PU1T and Chryseomicrobium imtechense MW 10T, Chryseomicrobiumamylolyticum JC16T were 38 and 32 % respectively. The G+C content of DNA of strain PU1T is 48.5 mol%. Based on the above-mentioned phenotypic and phylogenetic characteristics, strain PU1T represents a novel species of the genus Chryseomicrobium for which the name Chryseomicrobiumpalamuruense sp. nov. is proposed. The type strain is PU1T(=CCUG 59101T=JCM 16712T=KCTC 13722T=NBRC106750T). PMID- 27373686 TI - Neisseriae internalization by epithelial cells is enhanced by TLR2 stimulation. AB - Neisseria meningitidis (NM) is an opportunistic gram-negative human pathogen that colonizes the human nasopharyngeal epithelium. Asymptomatic carriage is common, but some meningococcal strains can invade nasopharyngeal epithelial cells and proceed to cause severe and often fatal infections. Invasion is predominantly driven by expression of bacterial virulence factors and host cell cognate receptors for bacterial recognition. Porins are among the Neisserial components involved in host cell activation and bacterial internalization processes. Similar to other virulence factors, porins present antigenic and structure variability among strains. Such sequence variability in the surface-exposed loop regions has been correlated to bacterial invasiveness and to variability in host cell responses via Toll-like receptor 2 (TLR2). Here, we examined whether TLR2 signaling by porins influences recovery of intracellular Neisseriae from epithelial cells in vitro. Our results show that TLR2 stimulation, either by the organism or exogenously, generally enhances Neisseriae internalization by epithelial cells. TLR2-driven intracellular signaling via ERK1/2, JNK and particularly NF-kappaB plays a role in this process. Based on these results, it is possible that expression of porin sequence variants that strongly induce TLR2 activation may be a mechanism to enhance the invasive features of pathogenic Neisseriae strains. PMID- 27373689 TI - A novel, lineage-primed prestalk cell subtype involved in the morphogenesis of D. discoideum. AB - Dictyostelium morphogenesis requires the tip, which acts as an organizer and conducts orchestrated cell movement and cell differentiation. At the slug stage the tip region contains prestalk A (pstA) cells, which are usually recognized by their expression of reporter constructs that utilize a fragment of the promoter of the ecmA gene. Here, using the promoter region of the o-methyl transferase 12 gene (omt12) to drive reporter expression, we demonstrate the presence, also within the pstA region, of a novel prestalk cell subtype: the pstV(A) cells. Surprisingly, a sub-population of the vegetative cells express a pstV(A): GFP marker and, sort out to the tip, both when developing alone and when co-developed with an excess of unmarked cells. The development of such a purified GFP-marked population is greatly accelerated: by precocious cell aggregation and tip formation with accompanying precocious elevation of developmental gene transcription. We therefore suggest that the tip contains at least two prestalk cell subtypes: the developmentally-specified pstA cells and the lineage-primed pstV(A) cells. It is presumably the pstV(A) cells that play the dominant role in morphogenesis during the earlier stages of development. The basis for the lineage priming is, however, unclear because we can find no correlation between pstV(A) differentiation and nutrient status during growth or cell cycle position at the time of starvation, the two known determinants of probable cell fate. PMID- 27373688 TI - The Genome of a Southern Hemisphere Seagrass Species (Zostera muelleri). AB - Seagrasses are marine angiosperms that evolved from land plants but returned to the sea around 140 million years ago during the early evolution of monocotyledonous plants. They successfully adapted to abiotic stresses associated with growth in the marine environment, and today, seagrasses are distributed in coastal waters worldwide. Seagrass meadows are an important oceanic carbon sink and provide food and breeding grounds for diverse marine species. Here, we report the assembly and characterization of the Zostera muelleri genome, a southern hemisphere temperate species. Multiple genes were lost or modified in Z. muelleri compared with terrestrial or floating aquatic plants that are associated with their adaptation to life in the ocean. These include genes for hormone biosynthesis and signaling and cell wall catabolism. There is evidence of whole genome duplication in Z. muelleri; however, an ancient pan-commelinid duplication event is absent, highlighting the early divergence of this species from the main monocot lineages. PMID- 27373690 TI - Dithiothreitol (DTT) rescues mitochondria from nitrofurantoin-induced mitotoxicity in rat. AB - Nitrofurantoin (N-(5-nitro-2-furfurylidine) 1-amino-hydantoine; NIT) is mainly used for the treatment of acute urinary tract infections. However, its administration can be associated with liver failure or cirrhosis. The aim of this study was to determine whether NIT is a mitochondrial toxicant, if so, what mechanism(s) is involved. The rat liver mitochondria were isolated and treated with different doses of NIT alone or in combination with a reagent of choice for protecting thiol groups, dithiothreitol (DTT). Several mitochondrial parameters, including succinate dehydrogenase activity (also called 3-(4,5-dimethylthiazol-2 yl) 2,5-diphenyl tetrazolium bromide assay), lipid peroxidation, superoxide dismutase activity, Reduced glutathione (GSH), and oxidized glutathione (GSSG), and GSSG (oxidized glutathione) levels were determined. The results from this study showed that simultaneous treatment of mitochondria with NIT and DTT significantly reduces the toxicity. Here, we provide evidence that mitochondrial dysfunction followed by depletion of reduced glutathione can be reversed by DTT administration. PMID- 27373691 TI - The Suppressive Effects of the Petroleum Ether Fraction from Atractylodes lancea (Thunb.) DC. On a Collagen-Induced Arthritis Model. AB - In Chinese traditional medicine, the rhizome of Atractylodes lancea (Thunb.) DC. (A. lancea) is used extensively for the treatment of several diseases such as rheumatic diseases, but its actions on rheumatoid arthritis have not been clarified. The purpose of this article was to investigate the pharmacological effect of an A. lancea rhizome extract on collagen-induced arthritis (CIA) in rats. The CIA model was induced by the injection of bovine type II collagen. The rats were orally administered the petroleum ether (PE) fraction of the A. lancea rhizome (0.82 and 1.64 mg/kg), methotrexate (0.3 mg/kg body weight), or a vehicle from day 7 to day 15 after the model was established. The histological examination and radiological observation showed that the PE fraction significantly reduced the inflammatory responses and collagen loss in the joints of the rats with CIA. The PE fraction inhibited the production of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-17, and IL-6 in the sera. Moreover, the treatment with the PE fraction in vivo was able to reduce the level of Beclin 1 protein in the synovial tissue of the rats. These results highlight the antiarthritic potential of the PE fraction of the A. lancea rhizome and provide further evidence of the involvement of Beclin 1 inhibition in the effects of the PE fraction of the A. lancea rhizome. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27373692 TI - ATP phosphoribosyltransferase from symbiont Entomomyces delphacidicola invovled in histidine biosynthesis of Nilaparvata lugens (Stal). AB - Histidine is an essential amino acid assumed to be synthesized by an obligatory yeast-like symbiont (Entomomyces delphacidicola str. NLU) in Nilaparvata lugens, an important rice pest. The adenosine-triphosphate phosphoribosyltransferase (ATP PRTase) facilities the committed first step of the histidine biosynthesis pathway. In the current study, a putative ATP-PRTase was cloned and verified to be of E. delphacidicola origin (EdePRTase). The expression of the gene was spatial and temporal universal with a profile that matched the distribution of the fungal symbiont. RNA interference aided the knockdown of the EdePRTase suppressed EdePRTase expression by 32-48 %. Hemolymph histidine level was also reduced followed by significant reduction of adult body weight. However, other performance characters including nymph development, survival, and adult sex ratio were not adversely affected by the knockdown. Furthermore, forced histidine exposure (through injection or feeding) significantly inhibited the EdePRTase mRNA levels at higher concentrations, but significantly increased EdePRTase expression levels at lower concentrations (feeding only). The significance of these findings support that the EdePRTase is from symbiont E. delphacidicola, and its involvement in histidine biosynthesis of N. lugens was discussed. The results provide a better understanding of EdePRTase and the encoded functional ATP-PRTase enzyme regulation in N. lugens and insects in general. PMID- 27373693 TI - Influenza C infections in Western Australia and Victoria from 2008 to 2014. AB - BACKGROUND: Influenza C is usually considered a minor cause of respiratory illness in humans with many infections being asymptomatic or clinically mild. Large outbreaks can occur periodically resulting in significant morbidity. OBJECTIVES: This study aimed at analyzing the available influenza C clinical samples from two widely separated states of Australia, collected over a 7-year period and to compare them with influenza C viruses detected in other parts of the world in recent years. PATIENTS/METHODS: Between 2008 and 2014, 86 respiratory samples that were influenza C positive were collected from subjects with influenza-like illness living in the states of Victoria and Western Australia. A battery of other respiratory viruses were also tested for in these influenza C-positive samples. Virus isolation was attempted on all of these clinical samples, and gene sequencing was performed on all influenza C-positive cultures. RESULTS AND CONCLUSIONS: Detections of influenza C in respiratory samples were sporadic in most years studied, but higher rates of infection occurred in 2012 and 2014. Many of the patients with influenza C had coinfections with other respiratory pathogens. Phylogenetic analysis of the full-length hemagglutinin-esterase-fusion (HE) gene found that most of the viruses grouped in the C/Sao Paulo/378/82 clade with the remainder grouping in the C/Kanagawa/1/76 clade. PMID- 27373694 TI - Practical applications of balanced steady-state free-precession (bSSFP) imaging in the abdomen and pelvis. AB - : Balanced steady-state free-precession (bSSFP) is an important pulse sequence that may be underutilized in abdominal and pelvic magnetic resonance imaging (MRI). bSSFP offers several advantages for abdominal and pelvic MRI that include: bright blood effects, a relative insensitivity to the dephasing effects which occur in structures with linear movement, low specific absorption rate (SAR), high signal-to-noise ratio (SNR), high spatial resolution, and rapid acquisition times. Bright blood effects can be exploited to diagnose or confirm vascular pathologies when gadolinium-enhanced imaging cannot be performed, is indeterminate, or is degraded by artifact. The relative insensitivity to dephasing artifact in areas of linear movement is useful when imaging the biliary, urinary, and gastrointestinal tracts where dephasing artifacts may mimic filling defects such as calculi or polyps. Low SAR imaging is important in pediatric and pregnant patients and may be useful in patients with medical devices that restrict SAR levels. Rapid acquisition times and high SNR are extremely valuable assets in abdominal and pelvic MRI and bSSFP (which can be performed as static or cine acquisitions) and can be added to most existing abdominal and pelvic protocols when deemed suitable without significantly prolonging examination times. This article reviews the fundamentals of bSSFP imaging, presents vascular and nonvascular applications of bSSFP in abdominal and pelvic MRI, and discusses potential limitations (including imaging artifacts) of bSSFP. LEVEL OF EVIDENCE: 5 J. Magn. Reson. Imaging 2017;45:11-20. PMID- 27373695 TI - Optimal cut-off value of alanine aminotransferase level to precisely estimate the presence of fatty liver in patients with poorly controlled type 2 diabetes. AB - Optimal cut-off value of ALT level to precisely estimate the presence of fatty liver was as low as 28.0 U/L. We should consider the possibility of fatty liver even when ALT level is within normal range in subjects with poorly controlled type 2 diabetes. PMID- 27373696 TI - A Highly Water-Tolerant Magnesium(II) Coordination Polymer Derived from a Flexible Layered Structure. AB - A two-dimensional (2D) layered Mg(II) coordination polymer (CP) with a high tolerance for H2 O was designed, synthesised, and crystallographically characterised. The synthesis was achieved by the introduction of a flexible 2D layered structure composed of Mg(II) ions and isonicotinate N-oxide ligands. Owing to its high H2 O tolerance, the obtained 2D layered structure has the flexibility to repeatedly adsorb a large amount of H2 O associated with interlayer expansion and enable the removal of H2 O from a H2 O/2-propanol mixed vapour. These results indicate that the CP could be an excellent dehydrating agent. PMID- 27373697 TI - The first description of how to take a picture from the microscope with an m phone. PMID- 27373699 TI - Topical herbal medicines for atopic eczema: a systematic review of randomized controlled trials. AB - Despite the availability of medicines with proven efficacy, many patients use complementary or alternative medicines (CAMs) to manage atopic eczema (AE). Due to the lack of objective information on topical CAMs, this systematic review evaluates the current evidence for the efficacy and safety of topical herbal preparations in AE. Using Cochrane systematic review methodology, PubMed, the Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (via EBSCO), MEDLINE (via EBSCO), Proquest Health and Medical Complete, GREAT and CAM-QUEST were searched from inception until June 2014. Bibliographies of retrieved studies were hand searched for further relevant trials. All controlled clinical trials of topical herbal medicines for AE in humans of any age were included regardless of the control intervention or randomization. Only English-language publications were considered. Eight studies met the inclusion criteria. Seven investigated extracts of single plants and one an extract from multiple plants. Only two studies that showed a positive effect were considered to have a low risk of bias across all domains (those of liquorice gel and Hypericum perforatum). In these two, the test product was reported to be superior to placebo. Despite variations in diagnostic criteria and lack of validated tools for outcome assessments in one of these, the promising results may warrant continued research in better-designed studies. No meta-analysis was performed due to heterogeneity in all studies. There is currently insufficient evidence of efficacy for any topical herbal extract in AE. Many studies had methodological flaws and even those showing efficacy were single trials with small patient cohorts. PMID- 27373698 TI - Progressive increase of resistance in Enterobacteriaceae urinary isolates from kidney transplant recipients over the past decade: narrowing of the therapeutic options. AB - BACKGROUND: Antibiotic resistance is an emerging phenomenon in kidney transplantation (KT). METHODS: We compared species distribution and antimicrobial susceptibility patterns in 1052 isolates from urine cultures obtained in 2 different cohorts of kidney transplant recipients in a single center (Cohort A: 189 patients undergoing KT between January 2002 and December 2004 [336 isolates]; Cohort B: 115 patients undergoing KT between January 2011 and December 2013 [716 isolates]). RESULTS: Asymptomatic bacteriuria accounted for most of the isolates (86.9% in Cohort A and 92.3% in Cohort B). Klebsiella pneumoniae (9.5% vs. 15.6%), Pseudomonas aeruginosa (1.8% vs. 7.9%), and Enterobacter cloacae (0.6% vs. 3.1%) were significantly more common in Cohort B. The isolation of K. pneumoniae in Cohort B was associated with the occurrence of acute pyelonephritis (9.8% of all K. pneumoniae isolates vs. 2.8% of the remaining uropathogens; P = 0.001). Non-susceptibility rates among Enterobacteriaceae in Cohort B were higher for every class of antibiotics (P <= 0.003) with the exception of fosfomycin. Compared to Cohort A, significant increases were seen in isolates from Cohort B for multidrug-resistant (MDR) (43.9% vs. 67.8%, respectively; P = 0.001), extended-spectrum beta-lactamase (ESBL)-producing (6.6% vs. 26.1%; P = 0.001), and carbapenemase-producing Enterobacteriaceae strains (0.0% vs. 5.0%; P = 0.001). Such differences were mostly attributable to K. pneumoniae (as 54.5% and 13.4% of isolates in Cohort B were ESBL-producing and carbapenemase-producing, respectively). MDR isolates were responsible for 69.1% of episodes of symptomatic urinary tract infection in Cohort B. CONCLUSION: The increase in resistance rates among Enterobacteriaceae uropathogens is significant and may have an effect on KT programs. PMID- 27373700 TI - Parent readiness for discharge from a tertiary care pediatric cardiology unit. AB - PURPOSE: This study aimed to measure parents' readiness for discharge from a pediatric cardiology/cardiac surgical inpatient unit. DESIGN AND METHODS: An observational study was conducted at a single tertiary care pediatric cardiac surgical program; parents received teaching from a discharge coordinator, bedside nurse, and, if needed, dietician and pharmacist. We surveyed parents/guardians on the day of discharge and 2 weeks later. RESULTS: We enrolled 181 participants, 53% with children <12 months of age. Length of hospital admission ranged from <=7 days (54%) to >4 weeks (8%). The most common diagnoses were ventricular septal defect (n = 39), atrial septal defect (n = 28), and coarctation of the aorta (n = 20). Home enteral feeding was required for 21 (12%) children, and 167 (92%) were discharged on medications. Nearly all parents (n = 173, 96%) felt they were ready to take their child home as planned. With respect to medical needs, problems to watch for, who and when to call, what their child was allowed and not allowed to do, and knowledge about follow-up, >90% of respondents rated their knowledge 8+ (range 0-10). Only 68% of respondents rated their knowledge >=8 regarding services available in their community. Twenty percent experienced challenges at home for which they felt unprepared. These included infection, pain, and gastrointestinal concerns. PRACTICAL IMPLICATIONS: Most parents felt ready for discharge following multidisciplinary teaching. Greater emphasis is needed on teaching families about services available in the community. Further study is required to determine which parents need additional support and education to avoid unanticipated challenges post discharge. PMID- 27373701 TI - Supplemental insurance reduces out-of-pocket costs in medicare observation services. PMID- 27373702 TI - Prolonged intravenous instead of oral antibiotics for acute hematogenous osteomyelitis in children. PMID- 27373703 TI - Hydration assessment among marathoners using urine specific gravity and bioelectrical impedance analysis. AB - The present study examined the relationship between urine specific gravity (Usg), body mass (BM) and bioelectrical impedance determined variables [total body water (TBW), per cent TBW and impedance values] before and after a marathon (n = 25 men; 10 women). A significant reduction in BM (pre: 71.2 +/- 12.4 kg; post: 69.6 +/- 12.0 kg; p < 0.001) and an increase in Usg (pre: 1.009 +/- 0.007; post: 1.018 +/- 0.009; p < 0.001) was observed post-race. TBW was not significantly decreased (pre: 42.7 +/- 8.0 kg; post: 42.4 +/- 7.7 kg) while per cent TBW significantly increased post-race (pre: 60.0 +/- 3.9%; post: 60.8 +/- 3.8%; p < 0.001). Impedance values were significantly greater post-race (pre: 3288 +/- 482; post: 3416 +/- 492 Omega; p < 0.001). There was no correlation between the change in Usg and the change in BM or any of the bioelectrical impedance determined variables. On average, BM, Usg and impedance values appear to express changes in hydration; however, the observed changes among these variables for a given individual appear to be inconsistent with one another. PMID- 27373704 TI - Quantitative assessment of chemical artefacts produced by propionylation of histones prior to mass spectrometry analysis. AB - Histone PTMs play a crucial role in regulating chromatin structure and function, with impact on gene expression. MS is nowadays widely applied to study histone PTMs systematically. Because histones are rich in arginine and lysine, classical shot-gun approaches based on trypsin digestion are typically not employed for histone modifications mapping. Instead, different protocols of chemical derivatization of lysines in combination with trypsin have been implemented to obtain "Arg-C like" digestion products that are more suitable for LC-MS/MS analysis. Although widespread, these strategies have been recently described to cause various side reactions that result in chemical modifications prone to be misinterpreted as native histone marks. These artefacts can also interfere with the quantification process, causing errors in histone PTMs profiling. The work of Paternoster V. et al. is a quantitative assessment of methyl-esterification and other side reactions occurring on histones after chemical derivatization of lysines with propionic anhydride [Proteomics 2016, 16, 2059-2063]. The authors estimate the effect of different solvents, incubation times, and pH on the extent of these side reactions. The results collected indicate that the replacement of methanol with isopropanol or ACN not only blocks methyl-esterification, but also significantly reduces other undesired unspecific reactions. Carefully titrating the pH after propionic anhydride addition is another way to keep methyl esterification under control. Overall, the authors describe a set of experimental conditions that allow reducing the generation of various artefacts during histone propionylation. PMID- 27373705 TI - Accelerated chemical shift imaging of hyperpolarized (13) C metabolites. AB - PURPOSE: Chemical shift imaging (CSI) has long been considered the gold standard method for in vivo hyperpolarized (13) C metabolite imaging because of its high sensitivity. However, CSI requires a large number of excitations so it is desirable to reduce the number of RF excitations and the total acquisition time. METHODS: Centric phase encoding and three-dimensional compressed sensing methods were adopted into a CSI acquisition to improve efficiency and reduce the number of excitations required for imaging hyperpolarized metabolites. The new method was implemented on a GE MR750W scanner for routine real time metabolic imaging experiments. RESULTS: Imaging results from phantoms and in vivo animals using hyperpolarized (13) C tracers demonstrate that when the entire CSI dataset is treated as a single object, compressed sensing can be satisfactorily applied to spectroscopic CSI. Centric k-space trajectory data collection also greatly improves the acquisition efficiency. This combination of compressed sensing CSI and acquisition time reduction was used to perform a hyperpolarized (13) C dynamic study. CONCLUSION: Compressed sensing can be satisfactorily applied to conventional CSI in hyperpolarized (13) C metabolite MR imaging to reduce the number of RF excitations and accelerate the imaging speed to take advantage of conventional CSI in providing high sensitivity and a large spectral bandwidth. Magn Reson Med 76:1033-1038, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27373706 TI - Dr Jekyll and Mrs Hyde: Risky hybrid sex by amphibian-parasitizing chytrids in the Brazilian Atlantic Forests. AB - In their article in this issue of Molecular Ecology, Jenkinson et al. () and colleagues address a worrying question-how could arguably the most dangerous pathogen known to science, Batrachochytrium dendrobatidis (Bd), become even more virulent? The answer: start having sex. Jenkinson et al. present a case for how the introduction into Brazil of the globally invasive lineage of Bd, BdGPL, has disrupted the relationship between native amphibians and an endemic Bd lineage, BdBrazil. BdBrazil is hypothesized to be native to the Atlantic Forest and so have a long co-evolutionary history with biodiverse Atlantic Forest amphibian community. The authors suggest that this has resulted in a zone of hybrid Bd genotypes which are potentially more likely to cause fatal chytridiomycosis than either parent lineage. The endemic-nonendemic Bd hybrid genotypes described in this study, and the evidence for pathogen translocation via the global amphibian trade presented, highlights the danger of anthropogenic pathogen dispersal. This research emphasizes that biosecurity regulations may have to refocus on lineages within species if we are to mitigate against the danger of new, possibly hypervirulent genotypes of pathogens emerging as phylogeographic barriers are breached. PMID- 27373707 TI - Co-evolution of marine worms and their chemoautotrophic bacterial symbionts: unexpected host switches explained by ecological fitting? AB - Mutualistic associations of bacteria and invertebrates are widespread and encompass an enormous diversity on the side of both partners. The advantages gained from the symbiosis favour reciprocal adaptations that increase the stability of the association and can lead to codiversification of symbiont and host. While numerous examples of a strictly vertical transfer of the symbionts from parent to offspring among intracellular associations abound, little is known about the fidelity of the partners in extracellular associations, where symbionts colonize the surface or body cavity of their host. In this issue of Molecular Ecology, Zimmermann et al. () investigated the evolutionary history of the symbiotic association between a monophyletic clade of sulphur-oxidizing Gammaproteobacteria and two distantly related lineages of marine worms (nematodes and annelids). The study supports the surprising conclusion that partner fidelity does not necessarily increase with the intimacy of the association. Ectosymbionts on the cuticle of the nematodes seem to be cospeciating with their hosts, whereas endosymbionts housed in the body cavity of the annelids must have originated multiple times, probably by host switching, from ectosymbionts of sympatric nematodes. This excellent case study on the evolutionary history of invertebrate microbe interactions supports the emerging concept that the co-evolutionary processes shaping such mutualistic symbioses include both codiversification and ecological fitting. PMID- 27373708 TI - A wide mesio-distal gap in sites of congenitally missing maxillary lateral incisors is related to a thin alveolar ridge. AB - OBJECTIVES: To evaluate (i) a possible correlation between the mesio-distal gap width and the alveolar ridge (AR) dimensions in patients missing the maxillary lateral incisor (I2) either due to agenesis or loss and (ii) the possibility of straightforward implant placement based on simulation. METHODS: The bucco-palatal width, area, and height of the AR at the position of I2, and the mesio-distal gap width between the central incisor and the canine, were assessed in maxillary CT scans of three groups: Patients with (i) agenesis of I2 (TA ; n = 40); (ii) I2 regularly erupted but extracted (TL ; n = 24); (iii) I2 regularly erupted and in situ (C; n = 40). Further, the possibility of straightforward placement of an implant 3 or 3.5 mm in diameter *10 mm in length, with 1 mm distance from the buccal and palatal plate of the alveolar ridge was simulated and compared to the actual treatment delivered. RESULTS: Bucco-palatal width and area of the AR at I2 and the adjacent teeth was significantly reduced in TA compared to TL and C. Further, in TA , but not TL , an increasing mesio-distal gap width between the central incisor and canine resulted in a significantly reduced bucco-palatal width of the edentulous AR. This impeded a simulated straightforward implant placement in >50% of the cases in TA , even with a reduced implant diameter. CONCLUSIONS: In patients congenitally missing I2, an increased mesio-distal gap width correlates significantly with reduced edentulous AR dimensions. A mesio distal gap of >6 mm was associated with thin bucco-palatal alveolar ridges, precluding straightforward implant placement in 60-80% of the cases. PMID- 27373709 TI - Differential expression of microRNAs in retinal vasculopathy caused by selective Muller cell disruption. AB - Vascular changes and photoreceptor degeneration are features of age-related macular degeneration, diabetic retinopathy and macular telangiectasis. We have profiled the differential expression of microRNAs and analysed their target genes in transgenic mice in which induced Muller cell disruption results in photoreceptor degeneration, vascular leak and deep retinal neovascularisation. We identified 9 miRNAs which were differentially expressed during the development of retinal neovascularization and chose miR-200b and its target genes for further study. Using qRT-PCR and western blot analysis, we found that downregulation of miR-200b was negatively correlated with its target genes, including zinc finger E box binding homeobox (ZEB) 1 and 2 and vascular endothelial growth factor receptor 1. Double immunofluorescence labelling revealed that the newly formed vessels in the outer retina were positive for ZEB2. Furthermore, intravitreal injections of a miR-200b-mimic and anti-miR-200b confirmed the negative correlation of miR-200b and its target gene expression. We also found that the miR-200b-mimic inhibited vascular leak in the established mild vascular lesions, whereas anti-miR-200b promoted it. Taken together, these data suggest that miR 200b may play a role in the development of intraretinal neovascularisation. PMID- 27373710 TI - Metal working fluid exposure and diseases in Switzerland. AB - BACKGROUND: Exposure to metal working fluids (MWF) is common in machining processes worldwide and may lead to diseases of the skin and the respiratory tract. OBJECTIVE: The aim of the study was to investigate exposure and diseases due to MWF in Switzerland between 2004 and 2013. METHODS: We performed descriptive statistics including determination of median and 90th percentile values of MWF concentrations listed in a database of Suva. Moreover, we clustered MWF-induced occupational diseases listed in a database from the Swiss Central Office for Statistics in Accident Insurance, and performed linear regression over time to investigate temporal course of the illnesses. RESULTS: The 90th percentile for MWF air concentration was 8.1 mg (aerosol + vapor)/m3 and 0.9 mg aerosol/m3 (inhalable fraction). One thousand two hundred and eighty skin diseases and 96 respiratory diseases were observed. CONCLUSIONS: This is the first investigation describing exposure to and diseases due to MWF in Switzerland over a timeframe of 10 years. In general, working conditions in the companies of this investigation were acceptable. Most measured MWF concentrations were below both the Swiss and most international occupational exposure limits of 2014. The percentage of workers declared unfit for work was 17% compared to the average of other occupational diseases (12%). PMID- 27373711 TI - Multimodal Mass Spectrometry Imaging of N-Glycans and Proteins from the Same Tissue Section. AB - On-tissue digestion matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can be used to record spatially correlated molecular information from formalin-fixed, paraffin-embedded (FFPE) tissue sections. In this work, we present the in situ multimodal analysis of N-linked glycans and proteins from the same FFPE tissue section. The robustness and applicability of the method are demonstrated for several tumors, including epithelial and mesenchymal tumor types. Major analytical aspects, such as lateral diffusion of the analyte molecules and differences in measurement sensitivity due to the additional sample preparation methods, have been investigated for both N-glycans and proteolytic peptides. By combining the MSI approach with extract analysis, we were also able to assess which mass spectral peaks generated by MALDI-MSI could be assigned to unique N-glycan and peptide identities. PMID- 27373713 TI - CO chemisorption at vacancies of supported graphene films: a candidate for a sensor? AB - We investigate CO adsorption at single vacancies of graphene supported on Ni(111) and polycrystalline Cu. The borders of the vacancies are chemically inert but, on the reactive Ni(111) substrate, CO intercalation occurs. Adsorbed CO dissociates at 380 K, leading to carbide formation and mending of the vacancies, thus preventing their effectiveness in sensor applications. PMID- 27373712 TI - Unexpected electronic structure of the alloyed and doped arsenene sheets: First Principles calculations. AB - We study the equilibrium geometry and electronic structure of alloyed and doped arsenene sheets based on the density functional theory calculations. AsN, AsP and SbAs alloys possess indirect band gap and BiAs is direct band gap. Although AsP, SbAs and BiAs alloyed arsenene sheets maintain the semiconducting character of pure arsenene, they have indirect-direct and semiconducting-metallic transitions by applying biaxial strain. We find that B- and N-doped arsenene render p-type semiconducting character, while C- and O-doped arsenene are metallic character. Especially, the C-doped arsenene is spin-polarization asymmetric and can be tuned into the bipolar spin-gapless semiconductor by the external electric field. Moreover, the doping concentration can effectively affect the magnetism of the C doped system. Finally, we briefly study the chemical molecule adsorbed arsenene. Our results may be valuable for alloyed and doped arsenene sheets applications in mechanical sensors and spintronic devices in the future. PMID- 27373714 TI - Calorimetric studies of the interactions of metalloenzyme active site mimetics with zinc-binding inhibitors. AB - The binding of drugs to metalloenzymes is an intricate process that involves several interactions, including binding of the drug to the enzyme active site metal, as well as multiple interactions between the drug and the enzyme residues. In order to determine the free energy contribution of Zn(2+) binding by known metalloenzyme inhibitors without the other interactions, valid active site zinc structural mimetics must be formed and binding studies need to be performed in biologically relevant conditions. The potential of each of five ligands to form a structural mimetic with Zn(2+) was investigated in buffer using Isothermal Titration Calorimetry (ITC). All five ligands formed strong 1 : 1 (ligand : Zn(2+)) binary complexes. The complexes were used in further ITC experiments to study their interaction with 8-hydroxyquinoline (8-HQ) and/or acetohydroxamic acid (AHA), two bidentate anionic zinc-chelating enzyme inhibitors. It was found that tetradentate ligands were not suitable for creating zinc structural mimetics for inhibitor binding in solution due to insufficient coordination sites remaining on Zn(2+). A stable binary complex, [Zn(BPA)](2+), which was formed by a tridentate ligand, bis(2-pyridylmethyl)amine (BPA), was found to bind one AHA in buffer or a methanol : buffer mixture (60 : 40 by volume) at pH 7.25 or one 8 HQ in the methanol : buffer mixture at pH 6.80, making it an effective structural mimetic for the active site of zinc metalloenzymes. These results are consistent with the observation that metalloenzyme active site zinc ions have three residues coordinated to them, leaving one or two sites open for inhibitors to bind. Our findings indicate that Zn(BPA)X2 can be used as an active site structural mimetic for zinc metalloenzymes for estimating the free energy contribution of zinc binding to the overall inhibitor active site interactions. Such use will help aid in the rational design of inhibitors to a variety of zinc metalloenzymes. PMID- 27373716 TI - Gold-catalyzed intermolecular formal (3+2) cycloaddition of stabilized vinyldiazo derivatives and electronically unbiased allenes. AB - The reaction of electronically unbiased allenes with alkenyldiazo compounds in the presence of gold catalysts provided alkylidenecyclopentene derivatives resulting from a formal intermolecular (3+2) carbocyclization. A stepwise mechanism involving initial activation of the diazo component and subsequent formation of an allyl cation intermediate has been proposed. This process represents the first intermolecular gold-catalyzed cycloaddition involving non activated allenes. PMID- 27373715 TI - Use of electrospinning and dynamic air focusing to create three-dimensional cell culture scaffolds in microfluidic devices. AB - Organs-on-a-chip has emerged as a powerful tool for pharmacological and physiological studies. A key part in the construction of such a model is the ability to pattern or culture cells in a biomimetic fashion. Most of the reported cells-on-a-chip models integrate cells on a flat surface, which does not accurately represent the extracellular matrix that they experience in vivo. Electrospinning, a technique used to generate sub-micron diameter polymer fibers, has been used as an in vitro cell culture substrate and for tissue engineering applications. Electrospinning of fibers directly into a fully sealed fluidic channel using a conventional setup has not been possible due to issues of confining the fibers into a discrete network. In this work, a dynamic focusing method was developed, with this approach enabling direct deposition of electrospun fibers into a fully sealed fluidic channel, to act as a matrix for cell culture and subsequent studies under continuous flowing conditions. Scanning electron microscopy of electrospun polycaprolactone fibers shows that this method enables the formation of fibrous layers on the inner wall of a 3D-printed fluidic device (mean fiber size = 1.6 +/- 0.6 MUm and average pore size = 113 +/- 19 MUm(2)). Cells were able to be cultured in this 3D scaffold without the addition of adhesion proteins. Media was pumped through the channel at high flow rates (up to 400 MUL min(-1)) during a dynamic cell culture process and both the fibers and the cells were found to be strongly adherent. A PDMS fluidic device was also prepared (from a 3D printed mold) and coated with polycaprolactone fibers. The PDMS device enables optical detection and confocal imaging of cultured cells on the fibers. Finally, macrophages were cultured in the devices to study how the fibrous scaffold can affect cell behavior. It was found that under lipopolysaccharide stimulation, macrophages cultured on PCL fibers inside of a channel secreted significantly more cytokines than those cultured on a thin layer of PCL in a channel or directly on the inner channel wall. Overall, this study represents a new approach for in vitro cell studies, where electrospinning can be used to easily and quickly create 3D scaffolds that can improve the culture conditions in microfluidic devices. PMID- 27373717 TI - Rheological characterizations and molecular dynamics simulations of self-assembly in an anionic/cationic surfactant mixture. AB - The formation of self-assemblies in mixed amino acid-based anionic N hexadecanoylglutamic acid (HGA) and cationic benzyldimethyl hexadecylammonium chloride (HDBAC) surfactants in aqueous solutions has been characterized. With rheological analysis, the viscoelastic properties of the mixed system are found to be completely dependent on the concentration of HDBAC. Molecular dynamics simulation results suggest that the morphology of self-assembly can be regulated from spherical micelles to wormlike micelles by the addition of HDBAC. The aromatic group of HDBAC adsorption provides a "charge-neutral" function to the micelle corona; the repulsive interactions within the head group of HGA are progressively screened and closely packed. In addition, the dynamic processes and formation mechanisms of self-assembly were analyzed in detail with molecular simulation techniques. PMID- 27373719 TI - The minimization of mechanical work in vibrated granular matter. AB - Experiments and computer simulations are carried out to investigate phase separation in a granular gas under vibration. The densities of the dilute and the dense phase are found to follow a lever rule and obey an equation of state. Here we show that the Maxwell equal-areas construction predicts the coexisting pressure and binodal densities remarkably well, even though the system is far from thermal equilibrium. This construction can be linked to the minimization of mechanical work associated with density fluctuations without invoking any concept related to equilibrium-like free energies. PMID- 27373718 TI - Diagnostic test accuracy of anti-glycopeptidolipid-core IgA antibodies for Mycobacterium avium complex pulmonary disease: systematic review and meta analysis. AB - Currently, an anti-glycopeptidolipid (GPL)-core IgA antibody assay kit for diagnosing Mycobacterium avium complex (MAC) is commercially available. We conducted this systematic review and meta-analysis to reveal the precise diagnostic accuracy of anti-GPL-core IgA antibodies for MAC pulmonary disease (MAC-PD). We systematically searched reports that could provide data for both sensitivity and specificity by anti-GPL-core IgA antibody for clinically diagnosed MAC-PD. Diagnostic test accuracy was estimated using the bivariate model. Of the 257 articles that we had found through primary search, we finally included 16 reports consisted of 1098 reference positive subjects and 2270 reference negative subjects. The diagnostic odds ratio was 24.8 (95% CI 11.6 52.8, I(2) = 5.5%) and the area under the hierarchical summary receiver operating characteristic curves was 0.873 (95% CI 0.837-0.913). With a cutoff value of 0.7 U/mL, the summary estimates of sensitivity and specificity were 0.696 (95% CI 0.621-0.761) and 0.906 (95% CI 0.836-0.951), respectively. The positive and negative likelihood ratios were 7.4 (95% CI 4.1-13.8) and 0.34 (95% CI 0.26 0.43), respectively. The demanding clinical diagnostic criteria may be a cause of false positive of the index test. The index test had good overall diagnostic accuracy and was useful to ruling in MAC-PD with the cutoff value. PMID- 27373720 TI - Comparing open and minimally invasive surgical procedures for oesophagectomy in the treatment of cancer: the ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) feasibility study and pilot trial. AB - BACKGROUND: Localised oesophageal cancer can be curatively treated with surgery (oesophagectomy) but the procedure is complex with a risk of complications, negative effects on quality of life and a recovery period of 6-9 months. Minimal access surgery may accelerate recovery. OBJECTIVES: The ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) study aimed to establish the feasibility of, and methodology for, a definitive trial comparing minimally invasive and open surgery for oesophagectomy. Objectives were to quantify the number of eligible patients in a pilot trial; develop surgical manuals as the basis for quality assurance; standardise pathological processing; establish a method to blind patients to their allocation in the first week post surgery; identify measures of postsurgical outcome of importance to patients and clinicians; and establish the main cost differences between the surgical approaches. DESIGN: Pilot parallel three-arm randomised controlled trial nested within feasibility work. SETTING: Two UK NHS departments of upper gastrointestinal surgery. PARTICIPANTS: Patients aged >= 18 years with histopathological evidence of oesophageal or oesophagogastric junctional adenocarcinoma, squamous cell cancer or high-grade dysplasia, referred for oesophagectomy or oesophagectomy following neoadjuvant chemo(radio)therapy. INTERVENTIONS: Oesophagectomy, with patients randomised to open surgery, a hybrid open chest and minimally invasive abdomen or totally minimally invasive access. MAIN OUTCOME MEASURE: The primary outcome measure for the pilot trial was the number of patients recruited per month, with the main trial considered feasible if at least 2.5 patients per month were recruited. RESULTS: During 21 months of recruitment, 263 patients were assessed for eligibility; of these, 135 (51%) were found to be eligible and 104 (77%) agreed to participate, an average of five patients per month. In total, 41 patients were allocated to open surgery, 43 to the hybrid procedure and 20 to totally minimally invasive surgery. Recruitment is continuing, allowing a seamless transition into the definitive trial. Consequently, the database is unlocked at the time of writing and data presented here are for patients recruited by 31 August 2014. Random allocation achieved a good balance between the arms of the study, which, as a high proportion of patients underwent their allocated surgery (69/79, 87%), ensured a fair comparison between the interventions. Dressing patients with large bandages, covering all possible incisions, was successful in keeping patients blind while pain was assessed during the first week post surgery. Postsurgical length of stay and risk of adverse events were within the typical range for this group of patients, with one death occurring within 30 days among 76 patients. There were good completion rates for the assessment of pain at 6 days post surgery (88%) and of the patient-reported outcomes at 6 weeks post randomisation (74%). CONCLUSIONS: Rapid recruitment to the pilot trial and the successful refinement of methodology indicated the feasibility of a definitive trial comparing different approaches to oesophagectomy. Although we have shown a full trial of open compared with minimally invasive oesophagectomy to be feasible, this is necessarily based on our findings from the two clinical centres that we could include in this small preliminary study. TRIAL REGISTRATION: Current Controlled Trials ISRCTN59036820. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 48. See the NIHR Journals Library website for further project information. PMID- 27373722 TI - Lactobacillus and health. PMID- 27373721 TI - Prognostic significance of Livin expression in nasopharyngeal carcinoma after radiotherapy. AB - PURPOSE: This study was designed to investigate the expression levels of the inhibitor of apoptosis protein Livin in nasopharyngeal cancer tissues and its prognostic significance in nasopharyngeal carcinoma after radiotherapy. MATERIAL AND METHODS: A total of 83 patients with nasopharyngeal carcinoma who received radiotherapy were enrolled in this study from January 2008 to October 2010. Livin expression in nasopharynx pathological specimens extracted from patients was detected by immunohistochemistry. A Kaplan-Meier analysis was conducted to explore the effects of clinicopathological features and Livin expression on the overall survival and progression-free survival of patients with nasopharyngeal carcinoma, and explore its prognosis relevance after radiotherapy. RESULTS: Of the 83 patients with nasopharyngeal carcinoma, the overall Livin positive expression rate was 65.1% (54 patients), and the overall response rate of radiotherapy was 81.9% (68 patients). Significant differences in radiotherapy efficacy were found between patients who did not express Livin and those who did (P<0.05). The Kaplan-Meier analysis showed that Livin expression, high clinical staging, cervical lymph node metastasis, high T-staging and high N-staging were significantly correlated with a decrease in the overall survival of patients with nasopharyngeal carcinoma (all P<0.05). A Cox multivariate survival analysis showed that Livin expression, clinical staging and N-staging were independent risk factors for the overall survival of patients with nasopharyngeal carcinoma treated with radiation (all P<0.05). Furthermore, Livin expression and clinical staging were independent risk factors for the progression-free survival of patients with nasopharyngeal carcinoma once radiotherapy was introduced (all P<0.05). CONCLUSION: Expression of Livin, an inhibitor of apoptosis proteins, may be closely linked with poor prognosis of nasopharyngeal carcinoma post radiotherapy and hence it may be a new therapeutic target in the treatment of the disease. PMID- 27373723 TI - Predicting coin flips: using resampling and hierarchical models to help untangle the NHL's shoot-out. AB - Roughly 14% of regular season National Hockey League games since the 2005-06 season have been decided by a shoot-out, and the resulting allocation of points has impacted play-off races each season. But despite interest from fans, players and league officials, there is little in the way of published research on team or individual shoot-out performance. This manuscript attempts to fill that void. We present both generalised linear mixed model and Bayesian hierarchical model frameworks to model shoot-out outcomes, with results suggesting that there are (i) small but statistically significant talent gaps between shooters, (ii) marginal differences in performance among netminders and (iii) few, if any, predictors of player success after accounting for individual talent. We also provide a resampling strategy to highlight a selection bias with respect to shooter assignment, in which coaches choose their most skilled offensive players early in shoot-out rounds and are less likely to select players with poor past performances. Finally, given that per-shot data for shoot-outs do not currently exist in a single location for public use, we provide both our data and source code for other researchers interested in studying shoot-out outcomes. PMID- 27373724 TI - Elements affecting food waste in the food service sector. AB - Avoidable food waste is produced in the food service sector, with significant ecological and economical impacts. In order to understand and explain better the complex issue of food waste a qualitative study was conducted on the reasons for its generation in restaurants and catering businesses. Research data were collected during three participatory workshops for personnel from three different catering sector companies in Finland. Based on synthesized qualitative content analysis, eight elements influencing production and reduction of food waste were identified. Results revealed the diversity of managing food waste in the food service sector and how a holistic approach is required to prevent and reduce it. It is crucial to understand that food waste is manageable and should be an integral component of the management system. The model of eight factors provides a framework for recognition and management of food waste in the food service sector. PMID- 27373725 TI - Implementation of a Standardized Clinical Assessment and Management Plan (SCAMP) for Food Challenges. AB - BACKGROUND: Oral food challenges (OFCs) are routinely used to confirm ongoing food allergy. Serum-specific IgE (sIgE) and skin prick testing (SPT) are imperfect predictors of which patients will pass OFCs. OBJECTIVE: The objective of this study was to describe the design and implementation of a Standardized Clinical Assessment and Management Plan (SCAMP) to study and iteratively improve sIgE and SPT thresholds to determine when and where to conduct OFCs for patients. METHODS: Allergists consulted recommended sIgE and SPT thresholds when ordering challenges although diversions were permitted. Criteria were iteratively improved after periodic analyses of challenge outcome and diversions. RESULTS: Over 3 years, allergists ordered 2368 food challenges for 1580 patients with histories of IgE-mediated reactions to food: 1386 in an outpatient clinic and 945 in a higher resource infusion center. Reactions to challenge were observed in 13% of clinic and 23% of infusion center challenges. Six patients challenged in clinic required treatment with epinephrine compared with 22 in the infusion center. The need for epinephrine was more common in patients with asthma-5% of asthmatic patients required epinephrine compared with 1% of nonasthmatic patients (P < .01). Recommended sIgE and SPT thresholds were incrementally changed and, using the control chart methodology, a significant decrease was noted in the proportion of challenges ordered in the higher resource location. CONCLUSIONS: By setting and continually refining sIgE and SPT recommendations using the SCAMP method, allergists can better determine the risk of severe reaction and triage patients to the appropriate setting for an OFC. PMID- 27373726 TI - Knowledge and Beliefs That Promote or Hinder Collaboration among Registered Dietitian Nutritionists and Certified Exercise Professionals-Results of a Survey. PMID- 27373727 TI - Evaluating the Applicability of Data-Driven Dietary Patterns to Independent Samples with a Focus on Measurement Tools for Pattern Similarity. AB - BACKGROUND: Diet is a key modifiable risk for many chronic diseases, but it remains unclear whether dietary patterns from one study sample are generalizable to other independent populations. OBJECTIVE: The primary objective of this study was to assess whether data-driven dietary patterns from one study sample are applicable to other populations. The secondary objective was to assess the validity of two criteria of pattern similarity. METHODS: Six dietary patterns Western (n=3), Mediterranean, Prudent, and Healthy- from three published studies on breast cancer were reconstructed in a case-control study of 973 breast cancer patients and 973 controls. Three more internal patterns (Western, Prudent, and Mediterranean) were derived from this case-control study's own data. STATISTICAL ANALYSIS: Applicability was assessed by comparing the six reconstructed patterns with the three internal dietary patterns, using the congruence coefficient (CC) between pattern loadings. In cases where any pair met either of two commonly used criteria for declaring patterns similar (CC >=0.85 or a statistically significant [P<0.05] Pearson correlation), then the true similarity of those two dietary patterns was double-checked by comparing their associations to risk for breast cancer, to assess whether those two criteria of similarity are actually reliable. RESULTS: Five of the six reconstructed dietary patterns showed high congruence (CC >0.9) to their corresponding dietary pattern derived from the case-control study's data. Similar associations with risk for breast cancer were found in all pairs of dietary patterns that had high CC but not in all pairs of dietary patterns with statistically significant correlations. CONCLUSIONS: Similar dietary patterns can be found in independent samples. The P value of a correlation coefficient is less reliable than the CC as a criterion for declaring two dietary patterns similar. This study shows that diet scores based on a particular study are generalizable to other populations. PMID- 27373728 TI - Spontaneous Right Coronary Artery Rupture and Acute Cardiac Tamponade in Behcet's Disease. AB - Coronary involvement in Behcet's disease is extremely rare and it can bring devastating consequences when it occurs. In this report, we present a 29-year-old male patient with Behcet's disease who developed rapidly changing and progressive coronary artery involvements under medical treatment. PMID- 27373729 TI - A Long Term Follow-up Study of Carriers of Hypertrophic Cardiomyopathy Mutations. AB - BACKGROUND: Adults who test positive for a mutation associated with the development of hypertrophic cardiomyopathy (HCM) but who have not manifested left ventricular hypertrophy (LVH) at the time of that diagnosis are now commonly identified in the era of genetic testing. There are little published data, however, on the long-term outlook for these phenotypically normal gene carriers. METHODS: Fifteen genotype positive/LVH negative patients with HCM were identified, seven of which were children when first diagnosed as gene carriers. Fourteen were followed up with clinical examinations, electrocardiography and echocardiography to determine if their clinical status had changed over time. Measurements included electrocardiographic changes, changes in wall thickness, diastolic function and global longitudinal stain. RESULTS: Ten participants were followed up for a total of 18 years, two for a total of 17 years, one for 11 years and one for 8 years. In addition, magnetic resonance imaging (MRI) studies were performed on 11 participants. Eleven participants carried a mutation for the MYBPC3 gene and three carried a mutation for the MYH7 gene. One patient, an adult at the time of initial investigation, developed phenotypic features of HCM on echocardiography and MRI, one an increase in wall thickness diagnostic for HCM only on MRI and another to be borderline for HCM on MRI. CONCLUSION: Hypertrophic cardiomyopathy can develop in adult life in carriers who may be negative for LVH at the time of gene diagnosis and warrants periodic supervision of carriers throughout their lives. PMID- 27373730 TI - Interhemispheric Asymmetry in Distribution of Infarct Lesions among Acute Ischemic Stroke Patients Presenting to Hospital. AB - BACKGROUNDS: This study aimed to investigate the possible asymmetric distribution of acute ischemic infarct lesions between patients with right-sided stroke versus left-sided stroke. METHODS: Acute ischemic stroke patients with unilateral infarct who underwent magnetic resonance imaging scan within 24 hours of onset were included. Infarct lesions were segmented on diffusion-weighted-imaging series and coregistered on the MNI-152 brain map. After flipping all lesions to the left side, voxel-based analysis was performed to evaluate for asymmetric distribution of infarct lesions using the stroke side as an independent variable. Symptom severity at admission was evaluated using the National Institutes of Health Stroke Scale score, and early clinical outcome with the modified Rankin Scale score at discharge. RESULTS: Of the 218 patients included in this study, 110 had right-sided ischemic infarcts whereas 108 had left-sided ischemic infarcts. There was no significant difference between patients with right-sided stroke versus left-sided stroke in terms of admission symptom severity, rate of treatment, stroke risk factors, and early clinical outcome. However, voxel-based analysis showed that ischemic infarcts of insular ribbon and lentiform nucleus were asymmetrically more common on the left-sided stroke compared to the right sided stroke. The admission symptoms were more severe among patients with left insular ribbon and lentiform nucleus infarct compared to those with infarction of mirrored right anatomical regions (P = .019). CONCLUSIONS: Acute ischemic infarcts of the left insular ribbon and lentiform nucleus are asymmetrically more common compared to mirrored counterpart regions, presumably due to more severe symptoms at presentation. Otherwise, distribution of symptomatic infarcts to the rest of the brain is roughly symmetric. PMID- 27373731 TI - Effect of DNA bending on transcriptional interference in the systems of closely spaced convergent promoters. AB - BACKGROUND: Over the past years there are increasing evidences that the interplay between two molecules of RNA polymerases, initiating transcription from promoters, oriented in opposite (convergent) directions, can serve as a regulatory factor of gene expression. The data concerning the molecular mechanisms of this so-called transcriptional interference (TI) are not well understood. METHODS: The interaction of RNA polymerase with circular DNA templates, containing the convergent promoters, was investigated in a series of in vitro transcription assays and atomic force microscopy (AFM). RESULTS: In this work, to study the mechanisms of transcription interference a series of plasmids with oppositely oriented closely spaced artificial promoters, recognized by Escherichia coli RNA polymerase, was constructed. The constructs differ in promoter structure and distance between the transcription start sites. We have demonstrated that the transcripts ratio (RNA-R/RNA-L) and morphology of convergent open promoter complexes (OPC) are highly dependent on the interpromoter distance. CONCLUSIONS: The obtained results allowed us to suggest the novel model of TI, which assumes the DNA bending upon binding of RNA polymerase with promoters and explains the phenomenon of complete inactivation of weaker promoter by the stronger one. GENERAL SIGNIFICANCE: The results show that the conformational transitions in DNA helix, associated with DNA bending upon binding of RNA polymerase with promoters, play crucial role in OPC formation in the systems with convergent promoters. PMID- 27373732 TI - Plastoglobules in algae: A comprehensive comparative study of the presence of major structural and functional components in complex plastids. AB - Plastoglobules (PG) are lipophilic droplets attached to thylakoid membranes in higher plants and green algae and are implicated in prenyl lipid biosynthesis. They might also represent a central hub for integration of plastid signals under stress and therefore the adaptation of the thylakoid membrane under such conditions. In Arabidopsis thaliana, PG contain around 30 specific proteins of which Fibrillins (FBN) and Activity of bc1 complex kinases (ABC1K) represent the majority with respect to both number and protein mass. However, nothing is known about the presence of PG in most algal species, which are responsible for about 50% of global primary production. Therefore, we searched the genomes of publicly available algal genomes for components of PG and the associated functional network in order to predict their presence and potential evolutionary conservation of physiological functions. We could identify homologous sequences for core components of PG, like FBN and ABC1K, in most investigated algal species. Furthermore, proteins at central and interesting positions within the PG functional coexpression network were identified. Phylogenetic sequence analysis revealed diversity within FBN and ABC1K sequences among algal species with complex plastids of the red lineage and large differences compared with green lineage species. Two types of FBN were detected that differ in their isoelectric point which seems to correlate with subcellular localization. Subgroups of FBN were shared between many investigated species and modeling of their 3D-structure implied a conserved structure. FBN and ABC1K are essential structural and functional components of PG. Their occurrence in investigated algal species suggests presence of PG therein and functions in prenyl lipid metabolism and adaptation of the thylakoid membrane that are conserved during evolution. PMID- 27373733 TI - Dynamic and modular gene regulatory networks drive the development of gametogenesis. AB - Gametogenesis is a complex process, which includes mitosis and meiosis and results in the production of ovum and sperm. The development of gametogenesis is dynamic and needs many different genes to work synergistically, but it is lack of global perspective research about this process. In this study, we detected the dynamic process of gametogenesis from the perspective of systems biology based on protein-protein interaction networks (PPINs) and functional analysis. Results showed that gametogenesis genes have strong synergistic effects in PPINs within and between different phases during the development. Addition to the synergistic effects on molecular networks, gametogenesis genes showed functional consistency within and between different phases, which provides the further evidence about the dynamic process during the development of gametogenesis. At last, we detected and provided the core molecular modules of different phases about gametogenesis. The gametogenesis genes and related modules can be obtained from our Web site Gametogenesis Molecule Online (GMO, http://gametsonline.nwsuaflmz.com/index.php), which is freely accessible. GMO may be helpful for the reference and application of these genes and modules in the future identification of key genes about gametogenesis. Summary, this work provided a computational perspective and frame to the analysis of the gametogenesis dynamics and modularity in both human and mouse. PMID- 27373734 TI - A comprehensive overview of computational resources to aid in precision genome editing with engineered nucleases. AB - Genome editing with engineered nucleases (zinc finger nucleases, TAL effector nucleases s and Clustered regularly inter-spaced short palindromic repeats/CRISPR associated) has recently been shown to have great promise in a variety of therapeutic and biotechnological applications. However, their exploitation in genetic analysis and clinical settings largely depends on their specificity for the intended genomic target. Large and complex genomes often contain highly homologous/repetitive sequences, which limits the specificity of genome editing tools and could result in off-target activity. Over the past few years, various computational approaches have been developed to assist the design process and predict/reduce the off-target activity of these nucleases. These tools could be efficiently used to guide the design of constructs for engineered nucleases and evaluate results after genome editing. This review provides a comprehensive overview of various databases, tools, web servers and resources for genome editing and compares their features and functionalities. Additionally, it also describes tools that have been developed to analyse post-genome editing results. The article also discusses important design parameters that could be considered while designing these nucleases. This review is intended to be a quick reference guide for experimentalists as well as computational biologists working in the field of genome editing with engineered nucleases. PMID- 27373735 TI - Screening and validation of lncRNAs and circRNAs as miRNA sponges. AB - Intensive research in past two decades has uncovered the presence and importance of noncoding RNAs (ncRNAs), which includes microRNAs (miRs) and long ncRNAs (lncRNAs). These two classes of ncRNAs interact to a certain extent, as some lncRNAs bind to miRs to sequester them. Such lncRNAs are collectively called 'competing endogenous RNAs' or 'miRNA sponges'. In this study, we screened for lncRNAs that may act as miRNA sponges using the publicly available data sets and databases. To uncover the roles of miRNA sponges, loss-of-function experiments were conducted, which revealed the biological roles as miRNA sponges. LINC00324 is important for the cell survival by binding to miR-615-5p leading to the de repression of its target BTG2. LOC400043 controls several biological functions via sequestering miR-28-3p and miR-96-5p, thereby changing the expressions of transcriptional regulators. Finally, we also screened for circular RNAs (circRNAs) that may function as miRNA sponges. The results were negative at least for the selected circRNAs in this study. In conclusion, miRNA sponges can be identified by applying a series of bioinformatics techniques and validated with biological experiments. PMID- 27373736 TI - Comparison of methods to detect differentially expressed genes between single cell populations. AB - We compared five statistical methods to detect differentially expressed genes between two distinct single-cell populations. Currently, it remains unclear whether differential expression methods developed originally for conventional bulk RNA-seq data can also be applied to single-cell RNA-seq data analysis. Our results in three diverse comparison settings showed marked differences between the different methods in terms of the number of detections as well as their sensitivity and specificity. They, however, did not reveal systematic benefits of the currently available single-cell-specific methods. Instead, our previously introduced reproducibility-optimization method showed good performance in all comparison settings without any single-cell-specific modifications. PMID- 27373737 TI - BrowseVCF: a web-based application and workflow to quickly prioritize disease causative variants in VCF files. AB - Following variant calling and annotation, accurate variant filtering is a crucial step to extract meaningful information from sequencing data and to investigate disease aetiology. However, the variant call format (VCF) used to store this information is not easy to handle for non-bioinformaticians. We present BrowseVCF, a flexible and intuitive software to enable researchers to browse and filter millions of variants in a few seconds. Key features include querying user defined gene lists, grouping samples for family or tumour/normal studies and exporting results in spreadsheet format. BrowseVCF's significant advantages over most existing tools include the ability to process data from any DNA sequencing experiment (exome, whole-genome and amplicons) and to correctly parse files annotated with Variant Effect Predictor. BrowseVCF can be used either locally on personal computers or as part of automated pipelines. Its user interface has been carefully designed to minimize tunable parameters. BrowseVCF is freely available from https://github.com/BSGOxford/BrowseVCF/releases/latest. PMID- 27373738 TI - More than carbon sequestration: Biophysical climate benefits of restored savanna woodlands. AB - Deforestation and climate change are interconnected and represent major environmental challenges. Here, we explore the capacity of regional-scale restoration of marginal agricultural lands to savanna woodlands in Australia to reduce warming and drying resulting from increased concentration of greenhouse gases. We show that restoration triggers a positive feedback loop between the land surface and the atmosphere, characterised by increased evaporative fraction, eddy dissipation and turbulent mixing in the boundary-layer resulting in enhanced cloud formation and precipitation over the restored regions. The increased evapotranspiration results from the capacity deep-rooted woody vegetation to access soil moisture. As a consequence, the increase in precipitation provides additional moisture to soil and trees, thus reinforcing the positive feedback loop. Restoration reduced the rate of warming and drying under the transient increase in the radiative forcing of greenhouse gas emissions (RCP8.5). At the continental scale, average summer warming for all land areas was reduced by 0.18 (o)C from 4.1 (o)C for the period 2056-2075 compared to 1986-2005. For the restored regions (representing 20% of Australia), the averaged surface temperature increase was 3.2 degrees C which is 0.82 degrees C cooler compared to agricultural landscapes. Further, there was reduction of 12% in the summer drying of the near-surface soil for the restored regions. PMID- 27373739 TI - Bioaccumulation and biotransformation of the beta-blocker propranolol in multigenerational exposure to Daphnia magna. AB - Multigenerational bioaccumulation and biotransformation activity and short-term kinetics (e.g., uptake and depuration) of propranolol in Daphnia magna were investigated at environmental concentration. The body burden and the major metabolite, desisopropyl propranolol (DIP), of propranolol were quantified using LC-MS/MS at the end of each generation after exposure for 11 generations. The accumulation of propranolol in D. magna at an environmental concentration of 0.2 MUg/L was not much different between the parent (F0) and the eleventh filial (F10) generation. However, at 28 MUg/L, its accumulation was 1.6 times higher-up to 18.9 MUg/g-in the F10 generation relative to the F0. In contrast to propranolol, DIP intensity gradually increased from F0 to F10 at 0.2 MUg/L, reflecting an increase in detoxification load and biotransformation performance; no increasing trend was observed at 28 MUg/L. The bioaccumulation factor (BAF) showed higher values with a lower concentration and longer period of exposure. The average values of the BAF for 21 days of long-term exposure in successive 11 generations were 440.4 +/- 119.7 and 1026.5 +/- 208.6 L/kg for 28 MUg/L and 0.2 MUg/L, respectively. These are comparable to the BAF of 192 for the short-term 72 h exposure at 28 MUg/L in the parent generation. It is also recommended that future studies for pharmaceutical ingredients be conducted on drug-drug interaction and structural characteristics on the prediction of biotransformation activity and bioaccumulation rate. PMID- 27373740 TI - Metal-induced rapid transformation of diamond into single and multilayer graphene on wafer scale. AB - The degradation of intrinsic properties of graphene during the transfer process constitutes a major challenge in graphene device fabrication, stimulating the need for direct growth of graphene on dielectric substrates. Previous attempts of metal-induced transformation of diamond and silicon carbide into graphene suffers from metal contamination and inability to scale graphene growth over large area. Here, we introduce a direct approach to transform polycrystalline diamond into high-quality graphene layers on wafer scale (4 inch in diameter) using a rapid thermal annealing process facilitated by a nickel, Ni thin film catalyst on top. We show that the process can be tuned to grow single or multilayer graphene with good electronic properties. Molecular dynamics simulations elucidate the mechanism of graphene growth on polycrystalline diamond. In addition, we demonstrate the lateral growth of free-standing graphene over micron-sized pre fabricated holes, opening exciting opportunities for future graphene/diamond based electronics. PMID- 27373741 TI - Corrigendum to "Cardiac sympathetic activity in 22q11.2 deletion syndrome" [Int. J. Cardiol. 212 (2016) 346-351]. PMID- 27373742 TI - Plasma Matrix Metalloproteinases in Patients With Stroke During Intensive Rehabilitation Therapy. AB - OBJECTIVE: To study plasma levels of matrix metalloproteinases (MMPs) as potential markers of recovery during intensive rehabilitation therapy (IRT) after stroke. DESIGN: Prospective and descriptive 3-month follow-up study. SETTING: Rehabilitation unit and research center. PARTICIPANTS: Patients with first-ever ischemic stroke (n=15) enrolled to IRT (>=3h/d and 5d/wk) and healthy volunteers (n=15) (N=30). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The primary outcome was to measure plasma MMP3, MMP12, and MMP13 levels and evaluate potential associations with motor/functional scales using a battery of tests (National Institutes of Health Stroke Scale, modified Rankin scale, Barthel Index, Fugl-Meyer Assessment, Functional Ambulation Categories, Medical Research Council scale, Chedoke Arm and Hand Activity Inventory, and the 10-m walk test) before IRT and at 1- and 3-month follow-ups. The secondary outcome was to evaluate the use of these MMPs as biomarkers as predictors of patient's outcome. RESULTS: MMP levels remained stable during the study period and were similar to those in the healthy volunteer group. However, baseline MMP12 and MMP13 levels were strongly associated with stroke severity and were found to be elevated in those patients with the poorest outcomes. Interestingly, plasma MMP3 was independent of baseline stroke characteristics but was found to be increased in patients with better motor/functional recovery and in patients with larger improvements during rehabilitation. CONCLUSIONS: MMPs might act as biologic markers of recovery during rehabilitation therapy related to their roles in both injury and tissue remodeling. Future confirmatory investigations in multicenter studies are warranted by our data. PMID- 27373743 TI - Difficulty in Identifying Factors Responsible for Pressure Ulcer Healing in Veterans With Spinal Cord Injury. AB - OBJECTIVE: To identify characteristics associated with pressure ulcer (PrU) healing for individuals with spinal cord injury (SCI). DESIGN: Secondary analysis of a large clinical trial's data for healing PrUs in individuals with SCI; prospective Delphi process was conducted with SCI and/or PrU experts. SETTING: Spinal cord injury centers. PARTICIPANTS: There were 629 screening and 162 treatment participants (N=791); 185 SCI clinicians/national PrU/wound care experts participated in the Delphi process. INTERVENTIONS: None. MAIN OUTCOME MEASURE: PrU healing of 50% and 100% at weeks 4 and 12. RESULTS: Poisson regression models using the top Delphi-recommended factors found that only ulcer stage consistently predicted 50% and 100% healing at weeks 4 and 12. Additionally, ischial/perineal location was associated with 33% higher likelihood of 50% healing at week 4. Patient noncompliance with treatment recommendations, the top-ranked Delphi factor, did not predict healing at week 4 or 12. Expanded models found that at week 4, baseline PrU size, PrU stage IV, PrU pain, and American Spinal Injury Association grade A significantly predicted 100% healing, while at week 12, only PrU stage (IV) significantly predicted 100% healing. Significant predictors of 50% healing at week 4 included baseline PrU size, stage, ischial/perianal location body mass index >30kg/m2, foul odor, and signs of infection. At week 12, PrU duration, paraplegia predicted 50% healing. SCI center identifiers consistently showed 2- to 5-fold variation in predicting 50% PrU healing at weeks 4 and 12. CONCLUSIONS: Delphi panel-recommended factors (eg, patient compliance) did not predict PrU healing. Reducing center-level variability in wound healing by learning from best practices should be a health system goal. PrU healing in SCI is still poorly understood, and future studies should focus on as yet unidentified or underappreciated factors. PMID- 27373744 TI - Multivariable Prediction of Return to Work at 6-Month Follow-Up in Patients With Mild to Moderate Acute Stroke. AB - OBJECTIVE: To investigate predictors of return to work (RTW) in a poststroke sample. DESIGN: Retrospective investigation of archival data from an inception cohort; acute care records and 6-month follow-up telephone interview data were obtained for analysis. SETTING: The Brain Recovery Core, a collaborative interinstitutional endeavor among an academic medical center, an acute care hospital, and a rehabilitation center. PARTICIPANTS: Data from patients with stroke from the Brain Recovery Core (N=298). Excluded cases included those with nontraditional and/or nonpaid job status, no National Institute of Health Stroke Scale (NIHSS) score, and an NIHSS score >16. Our final sample included 244 individuals (age range, 25-87y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Sociodemographic variables, stroke severity (NIHSS), and physical and neurocognitive measures. RESULTS: Adding predictor variables to our logistic regression model increased accuracy by approximately 18%. Greater independence in the FIM sit-to-stand movement predicted improved RTW rates (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.0-3.1), whereas nonwhite race (OR, 2.52; 95% CI, 1.16-5.47) and greater impairment on the NIHSS (OR, .88; 95% CI, .77-.99) predicted attenuated RTW rates. CONCLUSIONS: Valid measures of stroke severity and a clinician-rated sit-to-stand movement have utility in the acute prediction of later RTW in patients with mild to moderate stroke. Given the complexity of the RTW construct and the acute measurement of these variables, we believe that our findings can be used to inform clinical decisions and appropriately tailor rehabilitative strategies that improve quality of life for stroke survivors. PMID- 27373745 TI - Two Different Types of High-Frequency Physical Therapy Promote Improvements in the Balance and Mobility of Persons With Multiple Sclerosis. AB - OBJECTIVE: To evaluate the mobility and postural balance improvements that could be achieved in a cohort of persons with multiple sclerosis (MS) who participated in a motor adaptation protocol and a cohort of persons with MS who participated in a therapeutic exercise protocol. DESIGN: A cohort design, where subjects were evaluated before and after a 6-week intervention period. SETTING: Clinical laboratory setting. PARTICIPANTS: Individuals (N=42) with relapsing-remitting or secondary progressive MS (Expanded Disability Status Scale [EDSS] scores, 3.0 6.5) were initially screened for eligibility for participation in the study, from which those who fit the inclusion criteria (n=32) were enrolled in the study. Subjects were pseudorandomly assigned to a treatment group and matched based on EDSS scores. Fourteen individuals in the motor adaptation cohort (MAC) (mean age +/- SD, 52.6+/-9y; mean EDSS score +/- SD, 5.5+/-0.9) and 13 individuals in the therapeutic exercise cohort (TEC) (mean age +/- SD, 54.0+/-9y; mean EDSS score +/ SD, 5.3+/-0.9) completed the entire duration of their respective programs. INTERVENTIONS: Both cohorts completed their therapy twice a day, 5 days each week, for 6 weeks. Each session of the MAC program consisted of balance and gait training that encouraged new ways to adapt to challenging task demands. The TEC program was similar to a traditional exercise program. MAIN OUTCOME MEASURES: The Sensory Organization Test, 6-minute walk test, and gait spatiotemporal kinematics. RESULTS: Collectively, both treatment groups had improvements in postural balance (P=.001), walking endurance (P=.002), walking speed (P=.004), and step length (P<.001) after therapy. However, there were no statistical differences between the 2 treatment groups for any of the outcome variables (P values >.01). CONCLUSIONS: Our exploratory results suggest that a high frequency of physical therapy rather than a specific activity focus might be an important parameter for persons with MS. PMID- 27373746 TI - Reliability and Validity of Nonradiologic Measures of Forward Flexed Posture in Parkinson Disease. AB - OBJECTIVE: To examine the intertester reliability and validity of 5 nonradiologic measures of forward flexed posture in individuals with Parkinson disease (PD). DESIGN: Cross-sectional observational study. SETTING: University outpatient facility and community centers. PARTICIPANTS: Individuals (N=28) with PD with Hoehn and Yahr scores of 1 through 4. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Occiput to wall status, tragus to wall distance, C7 to wall distance, photographically derived trunk flexion angle, and inclinometric kyphosis measure. RESULTS: Participants were older adults (mean, 69.7+/-10.6y) with a 14-month to 15-year (mean, 5.9+/-3.5y) history of PD. Intertester reliability was excellent for all measures (kappa=.89 [cued condition] and 1.0 [relaxed condition] for occiput to wall status; intraclass correlation coefficients, .779-.897 for tragus to wall distance, C7 to wall distance, flexion angle, and inclinometric kyphosis measure). Convergent validity was supported for all measures by significant correlations between the same measures obtained during relaxed and cued conditions (eg, occiput to wall relaxed and cued) and for most measures by significant correlations between measures obtained under the same condition (eg, occiput to wall cued and tragus to wall cued). Significant correlations between tragus to wall distance, C7 to wall distance, flexion angle, and inclinometric kyphosis measure and the Unified Parkinson Disease Rating Scale item 28 (posture) also supported convergent validity. Significant differences between tragus to wall distance, C7 to wall distance, and inclinometric kyphosis measure values under relaxed and cued conditions supported known condition validity. Known group validity was demonstrated by significant differences in tragus to wall distance, C7 to wall distance, and inclinometric kyphosis measure obtained from individuals able and individuals unable to touch their occiput to wall when cued to stand tall. CONCLUSIONS: Tragus to wall distance, C7 to wall distance, and inclinometric kyphosis measure are reliable and valid nonradiologic measures of forward flexed posture in PD. PMID- 27373747 TI - Social Support and Actual Versus Expected Length of Stay in Inpatient Rehabilitation Facilities. AB - OBJECTIVES: To describe impairment-specific patterns in shorter- and longer-than expected lengths of stay in inpatient rehabilitation, and examine the independent effects of social support on deviations from expected lengths of stay. DESIGN: Retrospective cohort study. SETTING: Inpatient rehabilitation facilities. PARTICIPANTS: Medicare fee-for-service beneficiaries (N=119,437) who were discharged from inpatient rehabilitation facilities in 2012 after stroke, lower extremity fracture, or lower extremity joint replacement. INTERVENTION: Not applicable. MAIN OUTCOME MEASURE: Relative length of stay (actual minus expected). The Centers for Medicare & Medicaid Services posts annual expected lengths of stay based on patients' clinical profiles at admission. We created a 3 category outcome variable: short, expected, long. Our primary independent variable (social support) also included 3 categories: family/friends, paid/other, none. RESULTS: Mean +/- SD actual lengths of stay for joint replacement, fracture, and stroke were 9.8+/-3.6, 13.8+/-4.5, and 15.8+/-7.3 days, respectively; relative lengths of stay were -1.2+/-3.1, -1.6+/-3.7, and -1.7+/ 5.2 days. Nearly half of patients (47%-48%) were discharged more than 1 day earlier than expected in all 3 groups, whereas 14% of joint replacement, 15% of fracture, and 20% of stroke patients were discharged more than 1 day later than expected. In multinomial regression analysis, using family/friends as the reference group, paid/other support was associated (P<.05) with higher odds of long stays in joint replacement. No social support was associated with lower odds of short stays in all 3 impairment groups and higher odds of long stays in fracture and joint replacement. CONCLUSIONS: Inpatient rehabilitation experiences and outcomes can be substantially affected by a patient's level of social support. More research is needed to better understand these relationships and possible unintended consequences in terms of patient access issues and provider level quality measures. PMID- 27373748 TI - Marinicrinis sediminis gen. nov., sp. nov., isolated from marine sediment. AB - Novel Gram-stain-variable, bent rods or long filaments that were endospore forming, facultatively anaerobic, oxidase- and catalase-negative, and designated strain NC2-42T, were isolated from sediment on the coast of Weihai, China. Optimal growth occurred at 37 degrees C, pH 7.5 and with 2-3 % (w/v) NaCl. MK-7 was the sole respiratory quinone and meso-diaminopimelic acid was a diagnostic diamino acid in the peptidoglycan. The polar lipid profile of this novel isolate consisted of phosphatidylglycerol, phosphatidylethanolamine, an unknown phospholipid, an unknown phosphoaminolipid, two unknown glycolipids and an unknown lipid. The major cellular fatty acids in strain NC2-42T were anteiso-C15 : 0, iso-C16 : 0 and C16 : 0. The G+C content of the genomic DNA of strain NC2 42T was 58.11 mol% (HPLC). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain NC2-42T showed the highest similarity (92.32 %) to Paenibacillus profundus within the family Paenibacillaceae. Based on data from this taxonomic study using a polyphasic approach, the isolate is proposed to represent a novel species of a new genus within the family Paenibacillaceae, with the name Marinicrinis sediminis gen. nov., sp. nov. The type strain of the type species is NC2-42T (=KCTC 33676T=MCCC 1K01238T). PMID- 27373749 TI - Stain Normalization using Sparse AutoEncoders (StaNoSA): Application to digital pathology. AB - Digital histopathology slides have many sources of variance, and while pathologists typically do not struggle with them, computer aided diagnostic algorithms can perform erratically. This manuscript presents Stain Normalization using Sparse AutoEncoders (StaNoSA) for use in standardizing the color distributions of a test image to that of a single template image. We show how sparse autoencoders can be leveraged to partition images into tissue sub-types, so that color standardization for each can be performed independently. StaNoSA was validated on three experiments and compared against five other color standardization approaches and shown to have either comparable or superior results. PMID- 27373750 TI - Combination treatment with proteasome inhibitors and antiestrogens has a synergistic effect mediated by p21WAF1 in estrogen receptor-positive breast cancer. AB - Although antiestrogens significantly improve the survival of patients with ER positive breast cancer, therapeutic resistance remains a major limitation. The combinatorial use of antiestrogen with other therapies was proposed to increase their efficiency and more importantly, to prevent or delay the resistance phenomenon. In the present study, we addressed their combined effects with proteasome inhibitors (PIs). The effects of antiestrogens (hydroxyl-tamoxifen, raloxifen and fulvestrant) currently used in endocrine therapy were tested in combination with PIs, bortezomib or MG132, on the growth of three ER-positive breast cancer cell lines and in two cellular models of acquired antiestrogen resistance. When compared to single treatments, these combined treatments were significantly more effective in preventing the growth of the cell lines. The regulation of key cell cycle proteins, the cyclin-dependent kinase inhibitors, p21WAF1 and p27KIP1, were also studied. Bortezomib and MG132 drastically increased p21WAF1 expression through elevation of its mRNA concentration. Notably, p27KIP1 regulation was quite different from that of p21WAF1. Furthermore, the effect of bortezomib in combination with antiestrogen was evaluated on antiestrogen-resistant cell lines. The growth of two antiestrogen resistant cell lines appeared responsive to proteasome inhibition and was strongly decreased by a combined therapy with an antiestrogen. Collectively, these findings provide new perspectives for the use of PIs in combination with endocrine therapies for breast cancer and possibly to overcome acquired hormonal resistance. PMID- 27373751 TI - Influence of enrichment and isolation media on the detection of Campylobacter spp. in naturally contaminated chicken samples. AB - Investigating Campylobacter epidemiology requires adequate technique and media to ensure optimal culturing and accurate detection and isolation of Campylobacter strains. In the present study, we investigated the performances of three enrichment durations in Bolton broth (0, 24 and 48h) and compared four isolation media (mCCDA, Karmali, Butzler no. 2 and CampyFood agar (CFA)) for the detection of Campylobacter positive samples and the identification of Campylobacter species, from naturally contaminated broiler chicken samples (caeca, neck skin from carcasses, and skin from thighs). We compared our local results to those we obtained with samples from a European survey (caeca and neck skin) and a national survey (neck skin, thigh skin, and breast). Direct plating favored the detection of positive samples highly contaminated by Campylobacter (caeca and neck skin from carcasses) whatever the media. A longer enrichment reduced the rates of Campylobacter recovery except when using Butzler no. 2, more particularly for neck skin which background microflora was less important than in caeca. As a matter of fact, enrichment allowed a higher detection rate of positive samples with low Campylobacter contamination levels (breast, thigh skin), this detection being enhanced when using Butzler no. 2. When comparing the 3 other selective media, CFA was the 2nd most efficient media prior to mCCDA and Karmali. Interestingly, enrichment promoted the growth of Campylobacter coli but this promotion was least with Butzler no. 2 agar. Our study has confirmed the need to adapt the method to the types of samples for improving the detection of Campylobacter and that the method may affect the prevalence of the species. PMID- 27373752 TI - Erratum to: Relationship Dynamics and Partner Beliefs About Viral Suppression: A Longitudinal Study of Male Couples Living with HIV/AIDS (The Duo Project). PMID- 27373753 TI - Evaluation of geometrical effects of microneedles on skin penetration by CT scan and finite element analysis. AB - Computerized tomography scan (CT scan) imaging and finite element analysis were employed to investigate how the geometric composition of microneedles affects their mechanical strength and penetration characteristics. Simulations of microneedle arrays, comprising triangular, square and hexagonal microneedle base, revealed a linear dependence of the mechanical strength to the number of vertices in the polygon base. A laser-enabled, micromoulding technique was then used to fabricate 3*3 microneedle arrays, each individual microneedle having triangular, square or hexagonal base geometries. Their penetration characteristics into ex vivo porcine skin, were investigated for the first time by CT scan imaging. This revealed greater penetration depths for the triangular and square-based microneedles, demonstrating CT scan as a powerful and reliable technique for studying microneedle skin penetration. PMID- 27373754 TI - Unsaturated fatty acids lactose esters: cytotoxicity, permeability enhancement and antimicrobial activity. AB - Sugar based surfactants conjugated with fatty acid chains are an emerging broad group of highly biocompatible and biodegradable compounds with established and potential future applications in the pharmaceutical, cosmetic and food industries. In this work, we investigated absorption enhancing and antimicrobial properties of disaccharide lactose, monoesterified with unsaturated fatty acids through an enzymatic synthetic approach. After chemical and cytotoxicity characterizations, their permeability enhancing activity was demonstrated using intestinal Caco-2 monolayers through transepithelial electrical resistance (TEER) and permeability studies. The synthesized compounds, namely lactose palmitoleate (URB1076) and lactose nervonate (URB1077), were shown to exhibit antimicrobial activity versus eight pathogenic species belonging to Gram-positive, Gram negative microorganisms and fungi. PMID- 27373755 TI - Early nutrition transition in Haiti: linking food purchasing and availability to overweight status in school-aged children. AB - OBJECTIVE: The primary aim was to examine the association of socio-economic factors and diet with overweight (including obesity) among school-aged children in Haiti. The secondary aim was to describe food availability and the physical activity built environment in participating schools. DESIGN: This cross-sectional study examined baseline data from the intervention Mamba study assessing the effectiveness of a fortified peanut butter paste in school-aged children. Logistic regression modelling was used to test hypothesized factors in association with overweight status. SETTING: Six primary schools in Cap-Haitien, the second largest city in Haiti. SUBJECTS: Children (n 968) aged 3-13 years, in good health and enrolled in a participating school for the 2012/13 school year. RESULTS: Child age (adjusted OR (AOR); 95 % CI=0.25; 0.12, 0.56), child age squared (1.08; 1.03, 1.13), always purchasing food at school (3.52; 1.12, 11.08), mother's BMI (1.10; 1.04, 1.16) and household ownership of a bicycle (0.28; 0.11, 0.71) were significantly associated with overweight (likelihood ratio=36, P<0.0001). Consumption of fish was significantly lower in overweight children in the binary analysis (P=0.033) and improved the fit of the model. Schools had limited time and space for physical activity and foods sold by vendors were predominantly high in sugar or fat. CONCLUSIONS: To our knowledge the present study is the first to examine the covariates of childhood overweight or describe school food availability and physical activity built environments in Haiti. Further research is necessary to identify intervention targets and feasible, cost effective approaches for prevention of obesity in Haiti children. PMID- 27373756 TI - High-Throughput Sequencing Reveals Immunological Characteristics of the TRB-/IgH CDR3 Region of Umbilical Cord Blood. AB - OBJECTIVE: To compare the differences of immunological characteristics between newborn and adults, we performed high-throughput sequencing to reveal the diversity of umbilical cord blood and adult peripheral blood at both T-cell receptor beta chain (TRB) and immunoglobulin heavy chain (IGH) levels. STUDY DESIGN: High-throughput sequencing was performed to analyze the expression of TRB CDR3 and IGH-CDR3 in circulating T and B cells isolated from 20 healthy adults, 56 pregnant women, and 40 newborns. RESULTS: Our results revealed different immunological characteristics between newborn and adults, such as distinctive complementarity determining region 3 (CDR3) lengths, usage bias of variable and joining segments, random nucleotide addition, a large number of unique CDR3 peptides, and a greater repertoire diversity. Moreover, each newborn had a distinctive TRB-/IGH-CDR3 repertoire that was independent of the maternal immune status. CONCLUSIONS: This study presents comprehensive, unrestricted profiles of the TRB/IGH-CDR3 repertoire of newborns, pregnant women, and healthy adults at a sequence-level resolution. Our data may contribute to a better understanding of the immune system of newborns and benefit the efficient application of umbilical cord blood transplantation in future. PMID- 27373757 TI - RETRACTED: Evaluation of behavioral problems after prenatal dexamethasone treatment in Swedish adolescents at risk of CAH. AB - This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the authors due to technical errors that have called into question the reliability of the data used to inform the author's conclusions.All data on cognitive and behavioral outcomes in CAH and non-CAH cases, treated or not treated with DEX prenatally, were put into a single Excel database. The authors had in total four different patient groups for each age group (5-6 y, 7 17 y and 18-35 y). The database consisted of 237 cases in total and there were multiple columns for the different outcome measures.When the behavioral data for the sub-cohort described in this paper (first trimester treated non-CAH cases and healthy population controls, age 7-17 y) were copied to another sheet and compressed/modified in preparation for statistical analysis in SPSS, an error occurred. This technological issue caused rows to shift and the data from the different groups got mixed up. In particular, the non-CAH group versus the control group were "contaminated" with cases from the wrong patient group.The authors discovered this mistake when they started to analyse the data from the other sub-groups of patients, the CAH cases and the adult cohort, which was after their original results had already been published in Hormones and Behavior in this manuscript "Evaluation of behavioral problems after prenatal dexamethasone treatment in Swedish adolescents at risk of CAH".It then became apparent that the entire data set was unreliable and needed to be re-analysed which is what has motivated the retraction of this article. The authors have recently completed this re-analysis and the results have been published here: https://www.sciencedirect.com/science/article/pii/S0018506X17300752 PMID- 27373759 TI - Anthraquinones as a privileged scaffold in drug discovery targeting nucleotide binding proteins. AB - Anthraquinones are condensed aromatic hydrocarbons found naturally in medicinal plants and known for their potential medical and dye applications. Anthraquinones were developed as P2 receptor antagonists and ectonucleotidase inhibitors and feature very different characteristic properties regarding the binding site for anthraquinones. This demonstrates that the anthraquinone scaffold appears to behave as a privileged structure in medicinal chemistry targeting nucleotide binding proteins, and the substitution pattern, especially in the 4-position, can direct its interaction with specific targets. This article will cover the structure activity relationships of anthraquinones for three different targets: P2Y12 receptor, ecto-5'-nucleotidase and P2X2 receptor. PMID- 27373758 TI - Interaction of bisphenol A (BPA) and soy phytoestrogens on sexually dimorphic sociosexual behaviors in male and female rats. AB - Concerns have been raised regarding the potential for endocrine disrupting compounds (EDCs) to alter brain development and behavior. Developmental exposure to bisphenol A (BPA), a ubiquitous EDC, has been linked to altered sociosexual and mood-related behaviors in various animal models and children but effects are inconsistent across laboratories and animal models creating confusion about potential risk in humans. Exposure to endocrine active diets, such as soy, which is rich in phytoestrogens, may contribute to this variability. Here, we tested the individual and combined effects of low dose oral BPA and soy diet or the individual isoflavone genistein (GEN; administered as the aglycone genistin (GIN)) on rat sociosexual behaviors with the hypothesis that soy would obfuscate any BPA-related effects. Social and activity levels were unchanged by developmental exposure to BPA but soy diet had sex specific effects including suppressed novelty preference, and open field exploration in females. The data presented here reinforce that environmental factors, including anthropogenic chemical exposure and hormone active diets, can shape complex behaviors and even reverse expected sex differences. PMID- 27373760 TI - Open for collaboration: an academic platform for drug discovery and development at SciLifeLab. AB - The Science for Life Laboratory Drug Discovery and Development (SciLifeLab DDD) platform reaches out to Swedish academia with an industry-standard infrastructure for academic drug discovery, supported by earmarked funds from the Swedish government. In this review, we describe the build-up and operation of the platform, and reflect on our first two years of operation, with the ambition to share learnings and best practice with academic drug discovery centers globally. We also discuss how the Swedish Teacher Exemption Law, an internationally unique aspect of the innovation system, has shaped the operation. Furthermore, we address how this investment in infrastructure and expertise can be utilized to facilitate international collaboration between academia and industry in the best interest of those ultimately benefiting the most from translational pharmaceutical research - the patients. PMID- 27373761 TI - Innovating clinical kidney transplant education by a massive open online course. PMID- 27373762 TI - Neutral processes and species sorting in benthic microalgal community assembly: effects of tidal resuspension. AB - Benthic microalgae (BMA) provide vital food resources for heterotrophs and stabilize sediments with their extracellular secretions. A central goal in ecology is to understand how processes such as species interactions and dispersal, contribute to observed patterns of species abundance and distribution. Our objectives were to assess the effects of sediment resuspension on microalgal community structure. We tested whether taxa-abundance distributions could be predicted using neutral community models (NCMs) and also specific hypotheses about passive migration: (i) As migration decreases in sediment patches, BMA alpha-diversity will decrease, and (ii) As migration decreases, BMA community dissimilarity (beta-diversity) will increase. Co-occurrence indices (checkerboard score and variance ratio) were also computed to test for deterministic factors, such as competition and niche differentiation, in shaping communities. Two intertidal sites (mudflat and sand bar) differing in resuspension regime were sampled throughout the tidal cycle. Fluorometry and denaturing gradient gel electrophoresis were utilized to investigate diatom community structure. Observed taxa-abundances fit those predicted from NCMs reasonably well (R2 of 0.68-0.93), although comparisons of observed local communities to artificial randomly assembled communities rejected the null hypothesis that diatom communities were assembled solely by stochastic processes. No co-occurrence tests indicated a significant role for competitive exclusion or niche partitioning in microalgal community assembly. In general, predictions about relationships between migration and species diversity were supported for local community dynamics. BMA at low tide (lowest migration) exhibited reduced alpha-diversity as compared to periods of immersion at both mudflat and sand bar sites. beta-diversity was higher during low tide emersion on the mudflat, but did not differ temporally at the sand bar site. In between-site metacommunity comparisons, low- and high-resuspension sites exhibited distinct community compositions while the low-energy mudflats contained higher microalgal biomass and greater alpha-diversity. To our knowledge this is the first study to test the relevance of neutral processes in structuring marine microalgal communities. Our results demonstrate a prominent role for stochastic factors in structuring local BMA community assembly, although unidentified nonrandom processes also appear to play some role. High passive migration, in particular, appears to help maintain species diversity and structure communities in both sand and muddy habitats. PMID- 27373763 TI - Lifestyle treatments in cystic fibrosis: The NHS should pay. AB - With the NHS under increasing financial pressure and healthcare costs soaring year on year, it is perhaps not surprising that assessment agencies focus on cost effectiveness analysis when assessing new therapies. Such an approach does not however, always take sufficient account of treatment burden, lifestyle and patient choice and therefore new equally effective but perhaps "easier to take" formulations and faster delivery systems for current therapies do not always take precedence in current treatment guidelines. In arguing that the NHS should pay for so-called lifestyle treatments in cystic fibrosis the counterintuitive nature of some of the current decision making is discussed and a more holistic approach to improve NHS efficiency is presented. PMID- 27373764 TI - An expedited approach for sustained delivery of bone morphogenetic protein-7 to bone defects using gene activated fragments of subcutaneous fat. AB - BACKGROUND: Delivery of bone morphogenetic protein-7 (BMP-7) to bone defects can be improved by applying gene transfer methods. However, traditional ex vivo gene therapy approaches are cumbersome and costly, requiring the extraction and culturing of cells. Therefore, we evaluated a novel, expedited ex vivo BMP-7 gene transfer technology based on the use of fragments of subcutaneous fat tissue. METHODS: We created 5-mm mid-femoral bone defects in the right femora of 23 male, syngeneic Fischer 344 rats. Adipose tissue was harvested from the subcutaneous fat depot of two donor rats. Bone defects were treated with either unmodified fat (control group) or adenovirally BMP-7 transduced fat fragments (treatment group). Healing of bone defects was assessed by radiographs, microcomputed tomography (MUCT) and histology at 6 weeks after the implantation of fat tissue fragments. RESULTS: Radiographs, MUCT-imaging and histology revealed relevant bone formation in six out of 10 rats treated with BMP-7 activated fat grafts. Two of the defects were bridged. By contrast, femora of the control group receiving unmodified fat did not display signs of osseous healing. BMP-7 gene activated fat treatment led to a significantly higher bone volume (11.18 +/- 9.48 mm(3) ) than treatment with unmodified fat grafts (3.19 +/- 1.68 mm(3) ) (p = 0.008). CONCLUSIONS: Implantation of BMP-7 gene activated fat tissue fragments can elicit regeneration of large bone defects in rats and could become a clinically expeditious strategy for in vivo bone tissue engineering. However, gene expression must be improved in order to reliably induce osseous bridging of critical-size bone defects. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27373765 TI - Decline of multidrug-resistant Gram negative infections with the routine use of a multiple decontamination regimen in ICU. AB - OBJECTIVES: We have shown that the routine use of a multiple decontamination regimen with oropharyngeal and digestive polymyxin/tobramycin/amphotericin B plus mupirocin/chlorhexidine in intubated patients reduced all-cause acquired infections (AIs) in the intensive care unit (ICU). We now assessed the long-term impact of this strategy on AIs involving multidrug-resistant aerobic Gram negative bacilli (AGNB) and acquired episodes of extended-spectrum betalactamase (ESBL)-producing Enterobacteriaceae rectal carriage. METHODS: This was an observational single center study of all patients admitted to an ICU over 5 years (study population). Decontamination was given for the period of intubation and standard care otherwise. AIs and colonization rates were prospectively recorded. AIs rates were compared between the study period and a 1-year pre-intervention period. During study, trends were analyzed by semester using a Poisson regression model. RESULTS: The incidence rate of multidrug-resistant AGNB AIs was lower during the study (1.59 per 1000 patient-days, versus pre-intervention: 5.430/00, p < 0.001) and declined with time (adjusted OR = 0.85, 95 percent confidence interval 0.77-0.93, p < 0.001). ESBL-producing Enterobacteriaceae acquired colonization episodes (OR = 0.94 [0.88-1.00] P = 0.04) and the use of five major antibiotics (p < 0.001) also declined. CONCLUSION: A multiple decontamination regimen did not favor the emergence of multidrug-resistant AGNB. In contrast, infection and colonization rates declined with time. PMID- 27373766 TI - A family cluster of imported ZIKV cases: Viremia period may be longer than previously reported. PMID- 27373767 TI - Microbial biotechnology for the synthesis of (pro)vitamins, biopigments and antioxidants: challenges and opportunities. AB - Vitamins and related compounds, such as provitamins, biopigments and antioxidants, belong to those few chemicals that appeal in a positive way to most people. These terms sound synonymous to vitality, good health and mental strenght, even to the layman. Everyone of us needs his/her daily intake of (pro)vitamins and antioxidants, normally provided by a balanced and varied diet. However, current food habits or preferences, food availabilities, as well as food processing, preservation or cooking methodologies and technologies, do not always assure a sufficient balanced natural daily (pro)vitamin supply to a healthy individual, and even more so for a stressed or sick human being. Today, modern society is seldom confronted with the notorious avitaminoses of the past, well known to the Western World, but they do still occur frequently in overpopulated, war-ridden, poverty- or famine-struck regions on our globe, as well as for surprisingly large population groups in developed countries. PMID- 27373768 TI - Framing memories: How the retrieval query format shapes the neural bases of remembering. AB - The way memory questions are framed influences the information that is searched, retrieved, and monitored during remembering. This fMRI study aimed at clarifying how the format of the retrieval query shapes the neural basis of source recollection. During encoding, participants made semantic (pleasantness) or perceptual (number of letters) judgments about words. Subsequently, in a source memory test, the retrieval query was manipulated such that for half of the items from each encoding task, the retrieval query emphasized the semantic source (i.e., semantic query format: "Is this word from the pleasantness task?"), whereas for the other half the retrieval query emphasized the alternate, perceptual source (i.e., perceptual query format: "Is this word from the letter task?"). The results showed that the semantic query format was associated with higher source recognition than the perceptual query format. This behavioral advantage was accompanied by increased activation in several regions associated to controlled semantic elaboration and monitoring of internally-generated features about the past event. In particular, for items semantically encoded, the semantic query, relative to the perceptual query, induced activation in medial prefrontal cortex (PFC), hippocampal, parahippocampal and middle temporal cortex. Conversely, for items perceptually encoded, the semantic query recruited the lateral PFC and occipital-fusiform areas. Interestingly, the semantic format also influenced the processing of new items, eliciting greater L lateral and medial PFC activation. In contrast, the perceptual query format (versus the semantic format) only prompted greater activation in R orbitofrontal cortex and the R inferior parietal lobe, for items encoded in a perceptual manner and for new items, respectively. The results highlight the role of the retrieval query format in source remembering, showing that the retrieval query that emphasizes the semantic source promotes the use of semantic strategies via medial and L lateral PFC activations. These frontal activations are accompanied by differential recruitment of more posterior regions, depending on the type of information that had been encoded. PMID- 27373770 TI - Synthesis, Characterization and Antifungal Evaluation of Novel Thiochromanone Derivatives Containing Indole Skeleton. AB - Invasive fungal disease constitutes a growing health problem and development of novel antifungal drugs with high potency and selectivity against new fungal molecular targets are urgently needed. In order to develop potent antifungal agents, a novel series of 6-alkyl-indolo[3,2-c]-2H-thiochroman derivatives were synthesized. Microdilution broth method was used to investigate antifungal activity of these compounds. Most of them showed good antifungal activity in vitro. Compound 4o showed the best antifungal activity, which (inhibition of Candida albicans and Cryptococcus neoformans) can be achieved at the concentration of 4 ug/mL. Compounds 4b (inhibition of Cryptococcus neoformans), 4j (inhibition of Cryptococcus neoformans), 4d (inhibition of Candida albicans) and 4h (inhibition of Candida albicans) also showed the best antifungal activity at the concentrations of 4 ug/mL. The molecular interactions between 4o and the N myristoyltransferase of Candida albicans (PDB ID: 1IYL) were finally investigated through molecular docking. The results indicated that these thiochromanone derivatives containing indole skeleton could serve as promising leads for further optimization as novel antifungal agents. PMID- 27373769 TI - Advances in the Diagnosis and Management of Well-Differentiated and Intermediate Differentiated Neuroendocrine Tumors of the Lung. AB - Neuroendocrine tumors (NETs) are a rare, heterogeneous group of malignancies that arise from neuroendocrine cells throughout the body, with the lungs and GI tract being the most common sites of origin. Despite increasing incidence, awareness of lung NETs remains low among thoracic specialists who are often involved in the assessment and early treatment of these patients. Successful treatment requires accurate and timely diagnosis; however, classification can be challenging, particularly for well-differentiated and intermediate-differentiated lung NET types (typical carcinoids [TC] and atypical carcinoids [AC]). Diagnosis and management of lung NETs are further complicated by the nonspecificity of symptoms, variable natural history, and lack of high-level clinical evidence; a multidisciplinary approach is required, which has been shown to improve prognosis. Currently, surgery remains the only curative option for TC/AC. Inconsistencies between guideline recommendations for systemic therapies, especially for chemotherapy, result in a lack of consensus on a standardized treatment for unresectable disease. Recent data from the Phase III RAD001 in Advanced Neuroendocrine Tumors, Fourth Trial (RADIANT-4), which contained a large population of patients with advanced, well-differentiated, nonfunctional lung NETs in addition to those with GI NETs, found a reduced risk of disease progression and death with everolimus compared with placebo, leading to US approval of everolimus in these patient populations. This study is the first high level therapeutic evidence in patients with TC/AC, and everolimus is currently the only agent approved for treatment of TC/AC. Increased awareness, prompt diagnosis, and additional adequately powered controlled clinical trials of patients with well-differentiated and intermediate-differentiated lung NETs are needed to further improve evidence-based care. PMID- 27373771 TI - Decreased neuron loss and memory dysfunction in pilocarpine-treated rats pre exposed to hypoxia. AB - Preconditioning can induce a cascade of cellular events leading to neuroprotection against subsequent brain insults. In this study, we investigated the chronic effects of hypoxic preconditioning on spontaneous recurrent seizures (SRS), neuronal death, and spatial memory performance in rats subjected to pilocarpine (Pilo)-induced status epilepticus (SE). Rats underwent a short hypoxic episode (7% O2+93% N2; 30min on two consecutive days) preceding a 4-h SE (HSE group). Control groups were rats submitted to SE only (SE), rats subjected to hypoxia only (H) or normoxia-saline (C). Animals were monitored for the occurrence of SRS, and spatial memory performance was evaluated in the radial-arm maze. Hippocampal sections were analyzed for cell death and mossy fiber sprouting at 1 or 60days after SE. Compared to SE group, HSE had increased SE latency, reduced number of rats with SRS, reduced mossy fiber sprouting at 60days, and reduced cell death in the hilus and the CA3 region 1 and 60days after SE. Additionally, HSE rats had better spatial memory performance than SE rats. Our findings indicated that short hypoxic preconditioning preceding SE promotes long lasting protective effects on neuron survival and spatial memory. PMID- 27373772 TI - ISX-9 can potentiate cell proliferation and neuronal commitment in the rat dentate gyrus. AB - Adult hippocampal neurogenesis can be modulated by various physiological and pathological conditions, including stress, affective disorders, and several neurological conditions. Given the proposed role of this form of structural plasticity in the functioning of the hippocampus (namely learning and memory and affective behaviors), it is believed that alterations in hippocampal neurogenesis might underlie some of the behavioral deficits associated with these psychiatric and neurological conditions. Thus, the search for compounds that can reverse these deficits with minimal side effects has become a recognized priority. In the present study we tested the pro-neurogenic effects of isoxazole 9 (Isx-9), a small synthetic molecule that has been recently identified through the screening of chemical libraries in stem cell-based assays. We found that administration of Isx-9 for 14days was able to potentiate cell proliferation and increase the number of immature neurons in the hippocampal DG of adult rats. In addition, Isx 9 treatment was able to completely reverse the marked reduction in these initial stages of the neurogenic process observed in vehicle-treated animals (which were submitted to repeated handling and exposure to daily intraperitoneal injections). Based on these results, we recommend that future neurogenesis studies that require repeated handling and manipulation of animals should include a naive (non manipulated) control to determine the baseline levels of hippocampal cell proliferation and neuronal differentiation. Overall, these findings demonstrate that Isx-9 is a promising synthetic compound for the mitigation of stress-induced deficits in adult hippocampal neurogenesis. Future studies are thus warranted to evaluate the pro-neurogenic properties of Isx-9 in animal models of affective and neurological disorders associated with impaired hippocampal structural plasticity. PMID- 27373773 TI - Transparency in drug regulation: public assessment reports in Europe and Australia. AB - Openness and transparency are important considerations for medicines regulators, where public health is of paramount concern. As part of their commitment to transparency, the European Medicines Agency (EMA) and Therapeutic Goods Administration (TGA) in Australia publish information relating to their evaluation of medicines via public assessment reports. European Public Assessment Reports (EPARs) and Australian Public Assessment Reports (AusPARs) provide information about the considerations that led the regulator to approve or refuse the application. The reports summarise assessments by each regulator of the information provided on the quality, safety, and efficacy of the medicine under evaluation. Here, we describe the experiences of two established medicines regulators in publishing public assessment reports, and reflect on their future role in communicating medicines information. PMID- 27373775 TI - Report of ACPGBI President, 2016. PMID- 27373779 TI - High cell-density production of poly(3-hydroxybutyrate) in a membrane bioreactor. AB - Agro-industrial residues with a low carbon content, such as whey, stillage or wastewater from plant oil mills are abundant and cheap. However, they cannot be used directly in highly productive industrial poly(3-hydroxybutyrate) (P3HB) production, as the classical fed-batch fermentation strategy requires highly concentrated feed streams. This problem has been circumvented in this report by retaining the cells during the fermentation in the bioreactor using an external microfiltration module. Synthetic medium containing a glucose concentration of 50g/L was continuously fed to Cupriavidus necator, which converted the sugar to P3HB. With this setup we were able to achieve high productivities (3.10g P3HB/(Lh)) and reach high cell densities (148g/L) containing 76% P3HB, and obtained good yields (0.33g P3HB/g added glucose). The added sugar from the feed was instantly consumed by the bacteria, resulting in a negligible loss of sugar to the permeate. This approach creates the possibility of polyhydroxyalkanoate production from a range of cheap and easily available substrates, for which only waste water treatment or biogas production has been cost-competitive until now. PMID- 27373780 TI - The Mechanisms of Pharmacological Activities of Ophiocordyceps sinensis Fungi. AB - The entomopathogenic fungus Ophiocordyceps sinensis, formerly known as Cordyceps sinensis, has long been used as a traditional Chinese medicine for the treatment of many illnesses. In recent years its usage has increased dramatically because of the improvement of people's living standard and the emphasis on health. Such demands have resulted in over-harvesting of this fungus in the wild. Fortunately, scientists have demonstrated that artificially cultured and fermented mycelial products of O. sinensis have similar pharmacological activities to wild O. sinensis. The availability of laboratory cultures will likely to further expand its usage for the treatment of various illnesses. In this review, we summarize recent results on the pharmacological activities of the components of O. sinensis and their putative mechanisms of actions. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27373781 TI - Untargeted mass spectrometric approach in metabolic healthy offspring of patients with type 2 diabetes reveals medium-chain acylcarnitine as potential biomarker for lipid induced glucose intolerance (LGIT). AB - Offspring of type 2 diabetes (T2D) patients have increased risk to develop diabetes, due to inherited genetic susceptibility that directly interferes with the individual adaption to environmental conditions. We characterise T2D offspring (OSP) to identify metabolic risk markers for early disease prediction. Plasma of metabolically healthy OSP individuals (n = 43) was investigated after an oral lipid tolerance test (oLTT) by an untargeted mass spectrometric approach for holistic metabolome analyses. Two subgroups of OSP probands can be separated by oLTT, although not differing in general clinical parameters. Analyses of the plasma metabolome revealed mainly medium-chain acylcarnitines and very long-chain fatty acids with differential abundance in the subgroups. The study presented indicates that metabolically healthy OSP of T2D patients differ upon metabolic challenging in serum metabolite composition, especially medium-chain acylcarnitines. The difference suggest that postprandial lipid induced glucose intolerance (LGIT) may serve as a further valuable marker for early diabetes prediction. PMID- 27373782 TI - Epidemiology of pediatric hospitalizations at general hospitals and freestanding children's hospitals in the United States. AB - BACKGROUND: Children may be hospitalized at general hospitals or freestanding children's hospitals. Knowledge about how inpatient care differs at these hospitals is important to inform national research and quality efforts. OBJECTIVE: To describe the volume and characteristics of pediatric hospitalizations at acute care general and freestanding children's hospitals in the United States. DESIGN, PATIENTS, AND SETTING: Cross-sectional study of hospitalizations in the United States among children <18 years, excluding in hospital births, using the Healthcare Cost and Utilization Project's 2012 Kids' Inpatient Database. MEASUREMENT: We examined differences between hospitalizations at general and freestanding children's hospitals, applying weights to generate national estimates. Reasons for hospitalization were categorized using a pediatric grouper, and differences in hospital volumes were assessed for common diagnoses. RESULTS: A total of 1,407,822 (standard deviation 50,456) hospitalizations occurred at general hospitals, representing 71.7% of pediatric hospitalizations. Hospitalizations at general hospitals accounted for 63.6% of hospital days and 50.0% of pediatric inpatient healthcare costs. Median volumes of pediatric hospitalizations, per hospital, were significantly lower at general hospitals than freestanding children's hospitals for common medical and surgical diagnoses. Although the most common reasons for hospitalization were similar, the most costly conditions differed. CONCLUSIONS: In 2012, more than 70% of pediatric hospitalizations occurred at general hospitals in the United States. Differences in patterns of care at general hospitals and freestanding children's hospitals may inform clinical programs, research, and quality improvement efforts. Journal of Hospital Medicine 2016;11:743-749. (c) 2016 Society of Hospital Medicine. PMID- 27373783 TI - Incorporating 3D laparoscopy for the management of locally advanced cervical cancer: a comparison with open surgery. AB - PURPOSE: To test the effects of the implementation of 3D laparoscopic technology for the execution of nerve-sparing radical hysterectomy. METHODS: Thirty patients undergoing nerve-sparing radical hysterectomy via 3D laparoscopic (3D-LNSRH, n = 10) or open surgery (NSRH, n = 20) were studied prospectively. RESULTS: No significant differences were observed in baseline patient characteristics. Operative times were similar between groups. We compared the first 10 patients undergoing 3D-LNSRH with the last 20 patients undergoing NSRH. Baseline characteristics were similar between groups (p>0.2). Patients undergoing 3D-LNSRH had longer operative time (264.4 +/- 21.5 vs 217.2 +/- 41.0 minutes; p = 0.005), lower blood loss (53.4 +/- 26.1 vs 177.7 +/- 96.0 mL; p<0.001), and shorter length of hospital stay (4.3 +/- 1.2 vs 5.4 +/- 0.7 days; p = 0.03) in comparison to patients undergoing open abdominal procedures. No intraoperative complication occurred. One (10%) patient had conversion to open surgery due to technical difficulties and the inability to insert the uterine manipulator. A trend towards higher complication (grade 2 or worse) rate was observed for patients undergoing NSRH in comparison to 3D-LNSRH (p = 0.06). Considering only severe complications (grade 3 or worse), no difference was observed (0/10 vs 2/20; p = 0.54). CONCLUSIONS: 3D-laparoscopic nerve-sparing radical hysterectomy is a safe and effective procedure. The implementation of 3D laparoscopic technology allows the execution of challenging operations via minimally invasive surgery, thus reducing open abdominal procedure rates. Further large prospective studies are warranted. PMID- 27373784 TI - A case of pseudoachalasia hiding a malignant pleural mesothelioma. AB - PURPOSE: Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. We describe a case of MPM with an uncommon onset, characterized by pseudoachalasia as demonstrated with high-resolution manometry (HRM). METHODS: A 56-year-old man was referred to our hospital reporting worsening dysphagia. On the hypothesis of an esophageal motor disorder, the patient was referred for an HRM examination, which revealed features consistent with a diagnosis of type II achalasia. RESULTS: At the time of the first pneumatic dilation the endoscopist stopped the procedure in order to prevent perforation when he noticed only partial expansion of the pneumatic balloon. A CT scan and subsequent CT-guided excisional biopsy revealed an epithelioid pleural mesothelioma infiltrating the muscle wall. Given his good clinical condition, the patient was eligible for chemotherapy with cisplatin 75 mg/m2 and pemetrexed 500 mg/m2, resulting in a good response with partial remission of the disease and resolution of the dysphagia symptoms. CONCLUSIONS: Pseudoachalasia as the first or only manifestation of mesothelioma is a rare occurrence that may expose patients to the risk of diagnostic delay. Close attention should be paid whenever a patient with symptoms and signs consistent with achalasia shows unusual features. PMID- 27373785 TI - Open, laparoscopic, and robotic surgery for rectal cancer: medium-term comparative outcomes from a multicenter study. AB - PURPOSE: Several studies have demonstrated the oncologic equivalence of laparoscopic (LS) and open (OS) rectal cancer surgeries and have shown how challenging LS may become. Robotic surgery (RS) has emerged as a practical alternative, offering interesting advantages in comparison to both LS and OS. The aim of this study is to resolve the clinicopathologic outcome advantages of RS with respect to OS and LS techniques. METHODS: Patients with rectal cancer undergoing OS, RS, or LS were evaluated within the period from April 2009 to August 2011. The evaluations were carried out in 4 Italian hospitals. Perioperative clinicopathologic data, postoperative complications, and 3-year overall and disease-free survival (DFS) rates were analyzed. RESULTS: A total of 160 patients (94 male, 66 female) were included. A total of 105 patients underwent mini-invasive procedure (40 LS; 65 RS), whereas OS was performed in 55 patients. Anterior resection of rectal cancer was the most performed surgical procedure (139; 87%). Median operation time was significantly longer in the RS group (p<0.01). Regarding complication rates and quality of the surgical specimen evaluation, no statistical difference was found among the 3 groups. The shortest hospital stay (p<0.01) was obtained from the LS and RS groups. The median follow up was 33 months without any significant difference in overall and DFS rates. CONCLUSIONS: Although RS for rectal cancer requires more time to be performed than LS and OS techniques, the analysis shows comparatively the feasibility and safety of RS in terms of perioperative clinicopathologic and medium-term outcomes. PMID- 27373787 TI - Re-evaluation of 'drug-induced' erythema multiforme in the medical literature. PMID- 27373786 TI - Persistent T2*-hypointensity of the liver parenchyma after irradiation to the SPIO-accumulated liver: An imaging marker for responses to radiotherapy in hepatic malignancies. AB - PURPOSE: To determine whether T2*-weighted MRI has the ability to visualize the irradiated liver parenchyma and liver tumor after irradiation to the previously superparamagnetic iron oxide (SPIO)-accumulated liver. MATERIALS AND METHODS: We examined 24 liver tumor-bearing rats. Nine rats (Group 1) received 20 umol Fe/kg SPIO and subsequent 70-Gy irradiation to the tumor-bearing liver lobe. Four rats (Group 2) received SPIO and sham irradiation. Six rats (Group 3) received saline and irradiation. Finally, five rats (Group 4) received saline and sham irradiation. We acquired sequential 3 Tesla T2*-weighted images of the liver on day 7, and assessed MR image findings including signal intensity of the tumors and tumor-bearing liver lobes. RESULTS: In six rats in Group 1, tumors shrunk by 39-100% (303-0 mm3 ), and severely, well-defined hypointense irradiated areas were observed. In the other two rats, tumors enlarged by 25 and 172% (595 and 1148 mm3 ), and hypointense rings surrounded the tumors. The normalized relative signal intensity of the irradiated areas was significantly lower than that of the tumor (0.53 +/- 0.06 versus 0.94 +/- 0.06; P < 0.05). The severely, well-defined hypointense areas were not observed in the other groups. Histologically, necrotic regions dominated and minimal nonnecrotic tumor cells remained in irradiated areas. The number of CD68-positive cells was higher in irradiated areas than in nonirradiated areas. CONCLUSION: T2*-weighted MR imaging visualized the irradiated liver parenchyma as markedly, well-defined hypointense areas and liver cancer lesions as hyperintense areas only when SPIO was administered before irradiation. The visualization of the hypointense area was associated with tumor regression after irradiation. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:303-312. PMID- 27373788 TI - Work-family conflict, lack of time for personal care and leisure, and job strain in migraine: Results of the Brazilian Longitudinal Study of Adult Health (ELSA Brasil). AB - BACKGROUND: Work-family conflict and time scarcity may affect health. We investigated the association between these issues and migraine, taking into account job strain. METHODS: Baseline data from ELSA-Brasil (6,183 women; 5,664 men) included four indicators of work-family conflict: time- and strain-based interference of work with family (TB-WFC, SB-WFC), interference of family with work (FWC) and lack of time for personal care and leisure (LOT). Migraine was classified according to International Headache Society criteria. RESULTS: Among women, definite migraine was associated with SB-WFC (odds ratio [OR] = 1.28; 95% confidence interval [CI] 1.06-1.55), FWC (OR = 1.32; 1.00-1.75), and LOT (OR = 1.30; 1.08-1.58). Probable migraine was associated with SB-WFC (OR = 1.17; 1.00 1.36). High psychological job demands and low social support interacted with LOT in association with definite migraine. Among men, probable migraine was associated with LOT (OR = 1.34; 1.09-1.64), and there were interactions between job strain and WFC for probable migraine. CONCLUSIONS: Balancing the demands of professional and domestic spheres could be highly relevant in the management of migraines. Am. J. Ind. Med. 59:987-1000, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27373790 TI - Rapid Communications. PMID- 27373789 TI - 18th Annual Conference of the International Society for Bipolar Disorders & 8th Biennial Conference of the International Society for Affective Disorders, July 13 16, 2016, Amsterdam, The Netherlands. PMID- 27373791 TI - Insight on the Interaction of Methanol-Selective Oxidation Intermediates with Au- or/and Pd-Containing Monometallic and Bimetallic Core@Shell Catalysts. AB - Using density functional theory (DFT), the interaction of crucial molecules involved in the selective partial oxidation of methanol to methyl formate (MF) with monometallic Au and Pd and bimetallic Au/Pd and Pd/Au core@shell catalysts is systematically investigated. The core@shell structures modeled in this study consist of Au(111) and Pd(111) cores covered by a monolayer of Pd and Au, respectively. Our results indicate that the adsorption strength of the molecules examined as a function of catalytic surface decreases in the order of Au/Pd(111) > Pd(111) > Au(111) > Pd/Au(111) and correlates well with the d-band center model. The preadsorption of oxygen is found to have a positive impact on the selective partial oxidation reaction because of the stabilization of CH3OH and HCHO on the catalyst surface and the simultaneous intensification of MF desorption. On the basis of a dynamical matrix approach combined with statistical thermodynamics, we propose a simple route for evaluating the Gibbs free energy of adsorption as a function of temperature. This method allows us to anticipate the relative temperature stability of molecules involved in the selective partial oxidation of methanol to MF in terms of catalytic surface. PMID- 27373793 TI - Photoelectron spectroscopic and computational study of the PtMgH3,5(-) cluster anions. AB - The two cluster anions, PtMgH3(-) and PtMgH5(-), were studied by photoelectron spectroscopy and theoretical calculations. Experimentally-determined electron affinity (EA) and vertical detachment energy (VDE) values were compared with those predicted by our computations; excellent agreement was found. The calculated structures of PtMgH3(-) and PtMgH3 both exhibit eta2-bonded H2 moieties. Activation of these H2 moieties is implied by the elongation of their bond lengths relative to the bond length of free H2. The calculated structures of PtMgH5(-) and PtMgH5 both exhibit all-hydrogen, five-member, sigma-aromatic rings. These attributes are responsible for this anion's special stability. PMID- 27373792 TI - Working conditions, psychosocial environmental factors, and depressive symptoms among wage workers in South Korea. AB - BACKGROUND: In South Korea, the number of workers suffering from mental illnesses, such as depression, has rapidly increased. There is growing concern about depressive symptoms being associated with both working conditions and psychosocial environmental factors. OBJECTIVES: To investigate potential psychosocial environmental moderators in the relationship between working conditions and occupational depressive symptoms among wage workers. METHODS: Data were obtained from the wage worker respondents (n = 4,095) of the Korean National Health and Nutrition Examination Survey of 2009. First, chi-square tests confirmed the differences in working conditions and psychosocial characteristics between depressive and non-depressive groups. Second, multivariate logistic regression analysis was performed to examine the moderating effects of the psychosocial environmental factors between working conditions and depressive symptoms. RESULTS: After adjusting for potential covariates, the likelihood of depressive symptomatology was high among respondents who had dangerous jobs and flexible work hours compared to those who had standard jobs and fixed daytime work hours (OR = 1.66 and 1.59, respectively). Regarding psychosocial factors, respondents with high job demands, low job control, and low social support were more likely to have depressive symptoms (OR = 1.26, 1.58 and 1.61, respectively). CONCLUSIONS: There is a need to develop non-occupational intervention programs, which provide workers with training about workplace depression and improve social support, and the programs should provide time for employees to have active communication. Additionally, companies should provide employees with support to access mental healthcare thereby decreasing the occurrence of workplace depression. PMID- 27373794 TI - Effects of landscape anthropization on mosquito community composition and abundance. AB - Anthropogenic landscape transformation has an important effect on vector-borne pathogen transmission. However, the effects of urbanization on mosquito communities are still only poorly known. Here, we evaluate how land-use characteristics are related to the abundance and community composition of mosquitoes in an area with endemic circulation of numerous mosquito-borne pathogens. We collected 340 829 female mosquitoes belonging to 13 species at 45 localities spatially grouped in 15 trios formed by 1 urban, 1 rural and 1 natural area. Mosquito abundance and species richness were greater in natural and rural areas than in urban areas. Environmental factors including land use, vegetation and hydrological characteristics were related to mosquito abundance and community composition. Given the differing competences of each species in pathogen transmission, these results provide valuable information on the transmission potential of mosquito-borne pathogens that will be of great use in public and animal health management by allowing, for instance, the identification of the priority areas for pathogen surveillance and vector control. PMID- 27373795 TI - Liquid Nebulization-Ion Mobility Spectrometry Based Quantification of Nanoparticle-Protein Conjugate Formation. AB - Despite the importance of examining the formation of nanoparticle-protein conjugates, there is a dearth of routine techniques for nanoparticle-protein conjugate characterization. The most prominent change to a nanoparticle population upon conjugate formation is a shift in the nanoparticle size distribution function. However, commonly employed dynamic light scattering based approaches for size distribution characterization are ineffective for nonmonodisperse samples, and further they are relatively insensitive to size shifts of only several nanometers, which are common during conjugate formation. Conversely, gas phase ion mobility spectrometry (IMS) techniques can be used to reliably examine polydisperse samples, and are sensitive to ~1 nm size distribution function shifts; the challenge with IMS is to convert nanoparticle protein conjugates to aerosol particles without bringing about nonspecific aggregation or conjugate formation. Except in limited circumstances, electrospray based aerosolization has proven difficult to apply for this purpose. Here we show that via liquid nebulization (LN) with online, high-flow-rate dilution (with dilution factors up to 10 000) it is possible to aerosolize nanoparticle-protein conjugates, enabling IMS measurements of their conjugate size distribution functions. We specifically employ the LN-IMS system to examine bovine serum albumin binding to gold nanoparticles. Inferred maximum protein surface coverages (~0.025 nm(-2)) from measurements are shown to be in excellent agreement with reported values for gold from quartz crystal microbalance measurements. It is also shown that LN-IMS measurements can be used to detect size distribution function shifts on the order of 1 nm, even in circumstances where the size distribution function itself has a standard deviation of ~5 nm. In total, the reported measurements suggest that LN-IMS is a potentially simple and robust technique for nanoparticle-protein conjugate characterization. PMID- 27373796 TI - Adding muscle where you need it: non-uniform hypertrophy patterns in elite sprinters. AB - Sprint runners achieve much higher gait velocities and accelerations than average humans, due in part to large forces generated by their lower limb muscles. Various factors have been explored in the past to understand sprint biomechanics, but the distribution of muscle volumes in the lower limb has not been investigated in elite sprinters. In this study, we used non-Cartesian MRI to determine muscle sizes in vivo in a group of 15 NCAA Division I sprinters. Normalizing muscle sizes by body size, we compared sprinter muscles to non sprinter muscles, calculated Z-scores to determine non-uniformly large muscles in sprinters, assessed bilateral symmetry, and assessed gender differences in sprinters' muscles. While limb musculature per height-mass was 22% greater in sprinters than in non-sprinters, individual muscles were not all uniformly larger. Hip- and knee-crossing muscles were significantly larger among sprinters (mean difference: 30%, range: 19-54%) but only one ankle-crossing muscle was significantly larger (tibialis posterior, 28%). Population-wide asymmetry was not significant in the sprint population but individual muscle asymmetries exceeded 15%. Gender differences in normalized muscle sizes were not significant. The results of this study suggest that non-uniform hypertrophy patterns, particularly large hip and knee flexors and extensors, are advantageous for fast sprinting. PMID- 27373797 TI - Concentrations of buparvaquone in milk and tissue of dairy cows. AB - AIM: To determine the concentration of the anti-theilerial drug buparvaquone in the milk and tissue of dairy cattle following treatment with two different formulations, and to assess the effect of clinical theileriosis on the concentration of buparvaquone in milk. METHODS: Healthy lactating dairy cows (n=25) were injected once (Day 0) I/M with 2.5 mg/kg of one of two formulations of buparvaquone (Butalex; n=12 or Bupaject; n=13). Milk samples were collected from all cows daily until Day 35. Five cows were slaughtered on each of Days 56, 119, 147, 203 and 328, and samples of liver, muscle and injection site tissue collected. Milk samples were also collected from cows (n=14) clinically affected with theileriosis for up to 21 days after treatment with buparvaquone. Milk and tissue samples were analysed by liquid chromatography-mass spectrometry; limits of detection (LOD) were 0.00018 mg/kg for muscle and 0.00023 mg/L for milk. Concentrations of buparvaquone in milk and tissues were log10-transformed for analysis using multivariate models. RESULTS: In healthy cows, concentrations of buparvaquone in milk declined with time post-treatment (p<0.001), but were above the LOD in 11 of 25 cows at Day 35. Concentration in milk was higher one day after treatment in cows treated with Butalex than in cows treated with Bupaject, but not different thereafter (p=0.007). Concentrations of buparvaquone in muscle were below the LOD for four of five animals at Day 119 and for all animals by Day 147, but were above the LOD at the injection site of one cow, and in the liver of three cows at Day 328. Tissue concentrations did not differ with formulation nor was there a formulation by time interaction (p>0.3). Concentrations of buparvaquone in the milk of clinically affected animals were not different from those of healthy animals at 1 and 21 days post-treatment (p=0.72). Between 21 and 25 days post-treatment concentrations were below the LOD in 9/14 milk samples from clinically affected cows. CONCLUSIONS: Detectable concentrations of buparvaquone were found in the milk of some cows for at least 35 days and in the liver and injection site of some cows until at least 328 days after injection. There were no biologically meaningful differences in milk or tissue concentrations between the formulations, or in the milk concentrations for cows that were clinically affected compared with those that were healthy at the time of treatment. PMID- 27373798 TI - Factors favoring regain of the lost vertical spinal height through posterior spinal fusion in adolescent idiopathic scoliosis. AB - Height gain is a common beneficial consequence following correction surgery in adolescent idiopathic scoliosis (AIS), yet little is known concerning factors favoring regain of the lost vertical spinal height (SH) through posterior spinal fusion. A consecutive series of AIS patients from February 2013 to August 2015 were reviewed. Surgical changes in SH (DeltaSH), as well as the multiple coronal and sagittal deformity parameters were measured and correlated. Factors associated with DeltaSH were identified through Pearson correlation analysis and multivariate regression analysis. A total of 172 single curve and 104 double curve patients were reviewed. The DeltaSH averaged 2.5 +/- 0.9 cm in single curve group and 2.9 +/- 1.0 cm in double curve group. The multivariate regression analysis revealed the following pre-operative variables contributed significantly to DeltaSH: pre-op Cobb angle, pre-op TK (single curve group only), pre-op GK (double curve group only) and pre-op LL (double curve group only) (p < 0.05). Thus change in height (in cm) = 0.044 * (pre-op Cobb angle) + 0.012 * (pre-op TK) (Single curve, adjusted R(2) = 0.549) or 0.923 + 0.021 * (pre-op Cobb angle1) + 0.028 * (pre-op Cobb angle2) + 0.015 * (pre-op GK)-0.012 * (pre-op LL) (Double curve, adjusted R(2) = 0.563). Severer pre-operative coronal Cobb angle and greater sagittal curves were beneficial factors favoring more contribution to the surgical lengthening effect in vertical spinal height in AIS. PMID- 27373800 TI - Glycosylated platinum(iv) prodrugs demonstrated significant therapeutic efficacy in cancer cells and minimized side-effects. AB - Conjugates (A1-A5) of the Pt(iv) derivative (A6) with amino groups from peracetyl glucose, rhamnose and mannose with a propyl amino or ethyl amino linker at the reducing end were synthesized and exhibited significant therapeutic efficacy in tumour cells, especially for prostate cancer (PCa). The antitumor activities are greatly affected by glycosyl groups. Cytotoxic experiments in vitro indicated that the antitumor activities were increased by 5-fold when its Pt(iv) derivative was conjugated to S18 (IC50 = 4.82 +/- 0.45 MUM) and by 12-fold when conjugated to S21 (IC50 = 1.9 +/- 0.67 MUM). The mannose substituted Pt(iv) complexes A4 and A5 were also over an order of magnitude more potent towards HeLa, A549, MCF-7 and PC3 than cisplatin and oxaliplatin. Importantly, the glycosylated Pt(iv) derivatives A4 and A5 displayed potential safety for clinical therapeutic exposure with IC50 of 84 MUM and 169 MUM compared with cisplatin (IC50 = 8 MUM) to 3T3. Cellular uptake and DNA platination are higher than cisplatin and oxaliplatin. ESI-MS analysis of A5 binding to 5'-dGMP revealed that bifunctional DNA lesions were formed. The antitumor activities in vivo showed that the MTD and LD50 for A4 and A5 are nearly 4-fold higher than that of oxaliplatin indicating the potential safety for the glycosylated Pt(iv) complexes. PMID- 27373801 TI - Integrated on-chip mass spectrometry reaction monitoring in microfluidic devices containing porous polymer monolithic columns. AB - Chip-based microfluidics enable the seamless integration of different functions into single devices. Here, we present microfluidic chips containing porous polymer monolithic columns as a means to facilitate chemical transformations as well as both downstream chromatographic separation and mass spectrometric analysis. Rapid liquid phase lithography prototyping creates the multifunctional device economically. PMID- 27373799 TI - Acute kidney injury following cardiac surgery: current understanding and future directions. AB - Acute kidney injury (AKI) complicates recovery from cardiac surgery in up to 30 % of patients, injures and impairs the function of the brain, lungs, and gut, and places patients at a 5-fold increased risk of death during hospitalization. Renal ischemia, reperfusion, inflammation, hemolysis, oxidative stress, cholesterol emboli, and toxins contribute to the development and progression of AKI. Preventive strategies are limited, but current evidence supports maintenance of renal perfusion and intravascular volume while avoiding venous congestion, administration of balanced salt as opposed to high-chloride intravenous fluids, and the avoidance or limitation of cardiopulmonary bypass exposure. AKI that requires renal replacement therapy occurs in 2-5 % of patients following cardiac surgery and is associated with 50 % mortality. For those who recover from renal replacement therapy or even mild AKI, progression to chronic kidney disease in the ensuing months and years is more likely than for those who do not develop AKI. Cardiac surgery continues to be a popular clinical model to evaluate novel therapeutics, off-label use of existing medications, and nonpharmacologic treatments for AKI, since cardiac surgery is fairly common, typically elective, provides a relatively standardized insult, and patients remain hospitalized and monitored following surgery. More efficient and time-sensitive methods to diagnose AKI are imperative to reduce this negative outcome. The discovery and validation of renal damage biomarkers should in time supplant creatinine-based criteria for the clinical diagnosis of AKI. PMID- 27373802 TI - Opposite counter-ion effects on condensed bundles of highly charged supramolecular nanotubes in water. AB - Although ion specificity in aqueous solutions is well known, its manifestation in unconventional strong electrostatic interactions remains implicit. Herein, the ionic effects in dense packing of highly charged polyelectrolytes are investigated in supramolecular nanotube prototypes. Distinctive behaviors of the orthorhombic arrays composed of supramolecular nanotubes in various aqueous solutions were observed by Small Angle X-ray Scattering (SAXS), depending on the counter-ions' size and affiliation to the surface -COO(-) groups. Bigger tetra alkyl ammonium (TAA(+)) cations weakly bonding to -COO(-) will compress the orthorhombic arrays, while expansion is induced by smaller alkaline metal (M(+)) ions with strong affiliation to -COO(-). Careful analysis of the changes in the SAXS peaks with different counter/co-ion combinations indicates dissimilar mechanisms underlying the two explicit types of ionic effects. The pH measurements are in line with the ion specificity by SAXS and reveal the strong electrostatic character of the system. It is proposed that the small distances between the charged surfaces, in addition to the selective adsorption of counter ions by the surface charge, bring out the observed distinctive ionic effects. Our results manifest the diverse mechanisms and critical roles of counter-ion effects in strong electrostatic interactions. PMID- 27373803 TI - DNA barcoding identifies a cosmopolitan diet in the ocean sunfish. AB - The ocean sunfish (Mola mola) is the world's heaviest bony fish reaching a body mass of up to 2.3 tonnes. However, the prey M. mola consumes to fuel this prodigious growth remains poorly known. Sunfish were thought to be obligate gelatinous plankton feeders, but recent studies suggest a more generalist diet. In this study, through molecular barcoding and for the first time, the diet of sunfish in the north-east Atlantic Ocean was characterised. Overall, DNA from the diet content of 57 individuals was successfully amplified, identifying 41 different prey items. Sunfish fed mainly on crustaceans and teleosts, with cnidarians comprising only 16% of the consumed prey. Although no adult fishes were sampled, we found evidence for an ontogenetic shift in the diet, with smaller individuals feeding mainly on small crustaceans and teleost fish, whereas the diet of larger fish included more cnidarian species. Our results confirm that smaller sunfish feed predominantly on benthic and on coastal pelagic species, whereas larger fish depend on pelagic prey. Therefore, sunfish is a generalist predator with a greater diversity of links in coastal food webs than previously realised. Its removal as fisheries' bycatch may have wider reaching ecological consequences, potentially disrupting coastal trophic interactions. PMID- 27373804 TI - Highly conductive and flexible color filter electrode using multilayer film structure. AB - In this paper, a high performance flexible component that serves as a color filter and an electrode simultaneously is suggested. The suggested highly conductive and flexible color filter electrode (CFE) has a multilayer film structure composed of silver (Ag) and tungsten trioxide (WO3). The CFE maintained its color filtering capability even when the films were bent on a polyethylene terephthalate (PET) film. Low sheet resistance of the CFE was obtained using WO3 as a bridge layer that connects two Ag layers electrically. The sheet resistance was less than 2 Omega/sq. and it was negligibly changed after bending the film, confirming the flexibility of the CFE. The CFE can be easily fabricated using a thermal evaporator and is easily patterned by photolithography or a shadow mask. The proposed CFE has enormous potential for applications involving optical devices including large area devices and flexible devices. PMID- 27373805 TI - Crystal structure of a complex between beta-glucopyranose and a macrocyclic receptor with dendritic multicharged water solubilizing chains. AB - Using commercial screens for crystallization of biomolecules and taking advantage of the use of racemic crystallography allowed the production of X-ray quality single crystals and the elucidation at 1.08 A resolution of the solid state structure of a difficult target: the complex between glucopyranose and a water soluble macrocyclic receptor equipped with dendritic multianionic solubilizing chains. PMID- 27373807 TI - Effect of hand paddles and parachute on backstroke coordination and stroke parameters. AB - Hand paddles and parachutes have been used in order to overload swimmers, and consequently increase the propulsive force generation in swimming. However, their use may affect not only kinematical parameters (average speed, stroke length and stroke rate), but also time gaps between propulsive phases, assessed through the index of coordination (IdC). The objective of this study was to assess the effects of hand paddles and parachute use, isolated or combined, on kinematical parameters and coordination. Eleven swimmers (backstroke 50-m time: 29.16 +/- 1.43 s) performed four 15-m trials in a randomised order at maximal intensity: (1) without implements (FREE), (2) with hand paddles (HPD), (3) with parachute (PCH) and (4) with hand paddles plus parachute (HPD+PCH). All trials were video recorded (60 Hz) in order to assess average speed, stroke rate, stroke length, five stroke phases and index of coordination. When average swimming speed was compared to FREE, it was lower in PCH and HPD+PCH, and higher in HPD. Stroke rate decreased in all overloaded trials compared to FREE. The use of hand paddles and parachute increased and decreased stroke length, respectively. In addition, propulsive phase duration was increased when hand paddles were used, and time gaps shifted towards zero (no time gap), especially when hand paddles were combined with parachute. It is conceivable that the combined use of hand paddles and parachute, once allowing overloading both propulsive and resistive forces, provides a specific stimulus to improve muscle strength and propulsive continuity. PMID- 27373806 TI - Magnetic resonance imaging and computed tomography in the assessment of mandibular invasion by squamous cell carcinoma of the oral cavity. Influence on surgical management and post-operative course. AB - INTRODUCTION: Preoperative evaluation of the bone for invasion by oral cavity squamous cell carcinoma remains challenging. The aim of our study was to compare the accuracy of MRI and CT in detecting mandibular invasion by oral squamous cell carcinoma of the oral cavity, with histologic results as the reference standard, and to assess the influence on surgical management and post-operative course. PATIENTS AND METHODS: Patients who were clinically suspected of having bone invasion from oral cavity carcinoma were retrospectively included. A single senior radiologist reviewed MRI images and CT-scans, independently, for the presence or absence of mandibular invasion. The different surgical procedures were compared in terms of length of hospital stay and occurrence of surgical complications. RESULTS: Histological mandibular invasion occurred in 9 of 35 patients (25.7%). None of the preoperative imaging tests failed to detect bone invasion which resulted in a sensitivity of 100% for both MRI and CT. CT had slightly higher specificity than MRI (61.9% and 57.1% respectively) in predicting bone invasion, but no statistically significant difference was found (P=0.32). Specificity of CT and MRI was higher in the edentulous group (75% and 625% respectively) than in the dentate group (53.8% both), although no statistically significant difference was found. The length of hospital stay was increased in the segmental resection group (25+/-14.5 days) compared to the marginal resection group (13+/-4.6 days; P=0.004) and to the hemimandibulectomy group (15+/-7.2 days; P=0.014). Occurrence of post-operative complications, across all categories, was increased in the segmental resection group (70%, n=7/10; P=0.006) compared to the marginal resection group (8.3%, n=1/12) and to the hemimandibulectomy group (23.1%, n=3/13; P=0.04). CONCLUSION: MRI and CT being equivalent in detecting mandibular invasion, we suggest MRI as single imaging technique in the preoperative assessment of oral cavity SCC. Specificity could be increased if combined with PET/CT, in order to reduce the number of unnecessary mandibular interruptions. PMID- 27373808 TI - New graduate transition to practice: how can the literature inform support strategies? AB - Objective The transition to practice for new graduate health professionals has been identified as challenging, with health services typically adopting a range of support and management strategies to assist safe professional practice. Queensland's state-wide Occupational Therapy Clinical Education Program supporting new graduates within public sector health facilities conducted a narrative literature review to identify evidence-based recommended actions that would assist new graduate occupational therapists' to transition from student to practitioner. Method Searches of Medline, CINAHL and PubMed databases were used to locate articles describing or evaluating occupational therapy new graduate support actions. Results The themes of supervision, support and education emerged from the literature. Additionally, four interactions were identified as factors potentially influencing and being influenced by the processes and outcomes of supervision, support and education actions. The interactions identified were professional reasoning, professional identity, an active approach to learning and reflective practice. Conclusions The interactions emerging from the literature will serve to inform the delivery and focus of supervision, support and education for new graduate occupational therapists as they transition to practice. The results may have application for other health professions. What is known about the topic? The transition to practice for new graduate occupational therapists has been reported as challenging with health services implementing various actions to support and assist this transition. A previous literature review of recommended support strategies could not be found providing an impetus for this enquiry. What does this paper add? This narrative literature review identified three themes of actions supporting the transition of new graduates from student to practitioner. In addition to these themes of supervision, support and education, also emerging from the literature were factors identified as important to facilitating the transition of new graduates to the workplace. These factors, or interactions, are identified in this paper as professional reasoning, professional identity, an active approach to learning, and reflective practice. It is proposed that these interactions have an effect on and can be effected by supervision, support and education actions. The articulation between the interactions and the themes was a notable outcome emerging from this literature review. What are the implications for practitioners? This literature review will assist those planning actions to guide new graduates' transition into practice. It is proposed that the methods of implementing supervision, support and education actions are optimised by the identified interactions. PMID- 27373809 TI - Graphene-like 2D nanomaterial-based biointerfaces for biosensing applications. AB - Due to their unique structures and multifunctionalities, two-dimensional (2D) nanomaterials have aroused increasing interest in the construction of the novel biointerfaces for biosensing applications. Efforts in constructing novel biointerfaces led to exploit the more versatile and tunable graphene-like 2D nanomaterials (e.g. graphitic carbon nitride, boron nitride, transition metal dichalcogenides, and transition metal oxides) with various structural and compositional characteristics. This review highlights recent efforts in the design of graphene-like 2D nanomaterials and their derived biointerfaces and exploitation of their research on fluorescent sensors and a series of electrochemical sensors, including amperometric, electrochemiluminescence, photoelectrochemical and field-effect transistor sensors. Finally, we discuss some critical challenges and future perspectives in this field. PMID- 27373810 TI - Variant lumbrical musculature of the left hand: Clinico-anatomic elucidation. AB - Human hand is haughtily described in literature as 'revolution in evolution'. Lumbricals form an intricate part of its musculature playing a vital role in complex digital movements. By virtue of their origin from the volar aspect of palm and their insertion onto the dorsal aspect to the extensor digital expansion of the digits, lumbricals display complex actions flexing the metacarpophalangeal joint and extending the interphalangeal joints. Such manoeuvres of the digits are vital for skilful and precision movements. During routine dissection of the teaching program of undergraduate medical students, unusual origin and morphology of all the four lumbrical muscles in the left hand of a male cadaver was observed. Clinicians and hand surgeons should be aware of its variations while designing and dealing with hand surgeries. An attempt has been made to comprehend its clinical, embryological and phylogenetic aspects. PMID- 27373811 TI - Association between oestrogen receptor alpha (ESR1) gene polymorphisms and endometriosis: a meta-analysis of 24 case-control studies. AB - The PvuII (C > T), XbaI (A > G) and (TA)n polymorphisms of ESR1 gene are potentially associated with susceptibility to endometriosis. A meta-analysis was conducted to evaluate comprehensively the associations between endometriosis and ESR1 polymorphisms. Twenty-four studies, including 2740 cases and 3208 controls, were retrieved through searches of PubMed, EMBASE, Web of Science, CBM and CNKI. Meta-analyses showed that PvuII was associated with endometriosis only for stage I-III, only under a recessive model (OR = 1.53, 95% CI 1.05 to 2.21; P = 0.025). The short allele and TA13 of (TA)n were associated with a higher risk of endometriosis (ORS = 1.71, 95% CI 1.01 to 2.81, P = 0.046; ORTA13 = 1.45, 95% CI 1.06 to 1.97, PTA13 = 0.019); TA20 repeats was associated with a lower risk (OR = 0.36, 95% CI 0.16 to 0.80; P = 0.012). No statistically significant association was found in the XbaI polymorphism. This meta-analysis indicated that the PvuII and XbaI polymorphisms were not associated with the risk of endometriosis, whereas stage classification of endometriosis was likely to influence the association of PvuII polymorphism. The (TA)n polymorphisms might play roles in the susceptibility to, or protection against, the pathogenesis of endometriosis. PMID- 27373812 TI - Non-invasive ventilation by helmet more effective than face mask in acute respiratory distress syndrome. PMID- 27373814 TI - Glycolysis inhibition as a cancer treatment and its role in an anti-tumour immune response. AB - Increased glycolysis is the main source of energy supply in cancer cells that use this metabolic pathway for ATP generation. Altered energy metabolism is a biochemical fingerprint of cancer cells that represents one of the "hallmarks of cancer". The immune system can prevent tumour growth by eliminating cancer cells but this editing process ultimately results in poorly immunogenic cells remaining allowing for unchallenged tumour growth. In this review we look at the glycolysis pathway as a target for cancer treatments. We also examine the interplay between the glycolysis modulation and the immune response as an anti-cancer therapy. PMID- 27373813 TI - Hypoxia causes transgenerational impairments in reproduction of fish. AB - Hypoxia is amongst the most widespread and pressing problems in aquatic environments. Here we demonstrate that fish (Oryzias melastigma) exposed to hypoxia show reproductive impairments (retarded gonad development, decrease in sperm count and sperm motility) in F1 and F2 generations despite these progenies (and their germ cells) having never been exposed to hypoxia. We further show that the observed transgenerational reproductive impairments are associated with a differential methylation pattern of specific genes in sperm of both F0 and F2 coupled with relevant transcriptomic and proteomic alterations, which may impair spermatogenesis. The discovered transgenerational and epigenetic effects suggest that hypoxia might pose a dramatic and long-lasting threat to the sustainability of fish populations. Because the genes regulating spermatogenesis and epigenetic modifications are highly conserved among vertebrates, these results may also shed light on the potential transgenerational effects of hypoxia on other vertebrates, including humans. PMID- 27373815 TI - Prevalence and Clinical Significance of FLT3 Mutation Status in Acute Myeloid Leukemia Patients: A Multicenter Study. AB - BACKGROUND AND AIMS: FLT3-ITD mutations in acute myeloid leukemia (AML) are associated with a poor prognosis. In Latin America, little epidemiological data exist about these mutations and their influence on clinical evolution and prognosis. Standardization and well-established clinical correlation make FLT3 mutational analysis by molecular methods an invaluable tool to decide among treatment options and to determine AML prognosis. METHODS: We assessed the prevalence of FLT3-ITD mutations in 138 patients with AML at four hematology referral centers from Mexico and Colombia. Molecular methods based on polymerase chain reaction (PCR) were employed for determining FLT3-ITD status. RESULTS: Mutations were present in 28 patients indicating a prevalence of 20.28%. Median age was 47 years (5-96). The FLT3 mutation positive group was older, had higher WBC and hemoglobin values and lower platelet counts but without statistical significance. A not previously described mutation in the FLT3 gene was found in one patient involving a nucleotide exchange of timine for cytosine at the 66608 position. A high mortality was found in the FLT3-mutated group, 67.8 vs. 42.72% in the non-mutated group and median survival was 4.9 months vs. 20.4 months, p = 0.009. A mutated FLT3 did not confer poor prognosis to those with M3 AML. The mutated FLT3 population had poor overall survival (OS) despite hematoprogenitor stem cell transplantation (HSCT). CONCLUSION: Prevalence of FLT3-ITD mutation in AML was present in a proportion comparable to other populations and, when present, was associated with a very poor prognosis. PMID- 27373816 TI - Temporal windows of reproductive opportunity reinforce species barriers in a marine broadcast spawning assemblage. AB - Prezygotic isolating mechanisms act to limit hybridization and maintain the genetic identity of closely-related species. While synchronous intraspecific spawning is a common phenomenon amongst marine organisms and plays an important role in reproductive success, asynchronous spawning between potentially hybridizing lineages may also be important in maintaining species boundaries. We tested this hypothesis by comparing reproductive synchrony over daily to hourly timescales in a sympatric assemblage of intertidal fucoid algae containing selfing hermaphroditic (Fucus spiralis and Fucus guiryi) and dioecious (Fucus vesiculosus and Fucus serratus) species. Our results confirm that gametes are released on semi-lunar cycles in all species. However, sister species with different mating systems showed asynchronous spawning at finer circadian timescales, thus providing evidence for a partial reproductive barrier between hermaphroditic and dioecious species. Finally, our data also emphasize the ecological, developmental, and/or physiological constraints that operate to restrict reproduction to narrow temporal windows of opportunity in the intertidal zone and more generally the role of ecological factors in marine speciation. PMID- 27373817 TI - Extra-intestinal findings on magnetic resonance enterography in children with inflammatory bowel disease. AB - AIM: To determine the occurrence of extra-intestinal findings on magnetic resonance enterography (MRE) in a large cohort of children with known or suspected inflammatory bowel disease, characterise those findings, determine the technique and frequency of follow-up imaging, and associated costs. MATERIALS AND METHODS: Imaging reports from 757 MRE examinations in 671 children with known or suspected IBD from 2011 through 2012 were analysed retrospectively. Reported extra-intestinal findings were categorised by two radiologists in consensus as normal, normal variants or commonly seen findings without clinical significance, or abnormal. Prior imaging reports of the patients with abnormal findings were reviewed to identify which findings were new or substantially changed. Subsequent imaging examinations, their associated costs, and additional work-up of extra intestinal findings were recorded in each group. RESULTS: A total of 403 extra intestinal findings were reported in 290 MRE (38.3%) examinations performed in 269 children (40.1%). Of these, 189 (46.9%) findings were abnormal and new or significantly changed from prior imaging, 88 (21.8%) were abnormal and stable, 50 (12.4%) were normal variants or commonly seen findings with no clinical significance, and 76 (18.9%) were normal. Abnormal findings included 34.7% associated with IBD and 65.3% considered unrelated. Follow-up imaging was performed for 69 (17.1%) mostly abnormal findings in 94 patients (8.3%). Magnetic resonance imaging (51%) and ultrasound (28%) were the most commonly utilised imaging methods. CONCLUSION: MRE identifies a large number of previously unknown extra-intestinal abnormalities in children with known or suspected IBD, most unrelated to IBD. Although <10% of children having MRE undergo subsequent imaging of extra-intestinal abnormalities, given the rapid uptake of MRE in the paediatric population, emphasis should be given to avoiding techniques utilising ionising radiation at follow-up. PMID- 27373818 TI - Competition and screening with motivated health professionals. AB - Two hospitals compete for the exclusive services of health professionals, who are privately informed about their ability and motivation. Hospitals differ in their ownership structure and in the mission they pursue. The non-profit hospital sacrifices some profits to follow its mission but becomes attractive for motivated workers. In equilibrium, when both hospitals are active, the sorting of workers to hospitals is efficient and ability-neutral. Allocative distortions are decreasing in the degree of competition and disappear when hospitals are similar. The non-profit hospital tends to provide a higher amount of care and offer lower salaries than the for-profit one. PMID- 27373820 TI - The prognostic impact of thyroid function in pulmonary hypertension. AB - BACKGROUND: Thyroid disease is common in patients with pulmonary hypertension (PH), but its effect on long-term survival remains unknown. We examined the prognostic significance of thyroid hormone levels of free triiodothyronine (fT3) and free thyroxine and thyroid-stimulating hormone (TSH), and thyroid hormone replacement (THR) therapy in PH. METHODS: We conducted a retrospective analysis of 1,756 patients enrolled in the Giessen PH Registry in 1999 to 2013 with baseline thyroid function data; of these, 355, 533, 498, and 370 had pulmonary arterial hypertension (PAH); including 192 with idiopathic PAH (iPAH), PH due to left heart disease, PH due to lung diseases, and chronic thromboembolic PH (CTEPH), respectively. Thyroid function parameters associated with mortality were identified using Cox regression and Kaplan-Meier analyses. RESULTS: Transplant free survival at 1, 3, and 5 years was 86.7%, 65.6%, and 53.0%, respectively. Absence of THR therapy was an independent predictor of death in iPAH (multivariate hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.06-5.75). In patients without THR therapy, TSH levels in the lowest and highest quartiles (compared with the middle 2 quartiles) independently predicted death in iPAH (HR, 1.98; 95% CI, 1.07-3.67), whereas reduced fT3 levels were independently associated with increased death in PAH (HR, 8.30; 95% CI, 2.50-25.00) and CTEPH (HR, 1.79; 95% CI, 1.14-4.20). CONCLUSIONS: Thyroid hormone levels and THR therapy are prognostic factors in iPAH, PAH, and CTEPH. Prospective studies are warranted to verify the prognostic significance of thyroid function and the effect of THR therapy in PH. PMID- 27373819 TI - Longitudinal structural, functional, and cellular myocardial alterations with chronic centrifugal continuous-flow left ventricular assist device support. AB - BACKGROUND: Left ventricular assist device (LVAD) support triggers adaptations within failing hearts. The HeartWare (HeartWare International, Inc., Framingham, MA) LVAD exhibits different flow profiles and afterload dependence compared with previous-generation devices, which may alter remodelling patterns. We sought to characterize myocardial adaptation to third-generation centrifugal-flow LVADs at a functional, hemodynamic, and structural level in addition to profiling transcriptomal changes using next-generation sequencing platforms. METHODS: We studied 37 patients supported with the HeartWare device with paired measurements of invasive hemodynamics, serial longitudinal left ventricular (LV) and right ventricular (RV) 3-dimensional echocardiography, and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) measurements. Paired samples for comparison of histologic myocardial cellular size and transcriptomal profiling were performed on specimens taken at pump implant and transplantation. RESULTS: The mean support duration was 280 +/- 163 days. Mechanical unloading after HeartWare support resulted in reduced filling pressures (mean pulmonary capillary wedge pressure 27.1 +/- 6.6 to 14.8 +/- 5.1 mm Hg, p < 0.0001). Mean LV cardiomyocyte cell size decreased from 2,789.7 +/- 671.8 to 2,290.8 +/- 494.2 MUm2 (p = 0.02). LV and RV ejection fractions improved significantly (24% +/- 8% to 35% +/- 9% [p < 0.001] and 35% +/- 11% to 40% +/- 8% [p < 0.02], respectively). NT-proBNP levels fell 4.8-fold by Day 90 after support, consistent with a decrease in LV wall stress. Despite these concordant beneficial findings, the microRNA transcriptome did not change significantly across the group. CONCLUSIONS: Reverse remodelling is evident at multiple levels with chronic HeartWare support in the absence of changes in the microRNA transcriptome. Successful myocardial unloading is associated with a decrease in wall stress, regression of cardiomyocyte hypertrophy, and an improvement in LV and RV ejection fractions. PMID- 27373821 TI - Changing demographics and outcomes of lung transplantation recipients with cystic fibrosis. AB - BACKGROUND: Cystic fibrosis (CF) is one of the most common diagnoses in adult and pediatric patients undergoing lung transplantation (LTx). A changing pattern of indications for LTx among patients with CF has been noted. This study analyzes the prevalence and characteristics of patients with CF who underwent LTx in the current era. METHODS: A retrospective analysis was performed using data from the United Network of Organ Sharing database of all LTx performed from 1999 to 2013 (N = 20,345). Sub-analyses focused on children (<18 years old). Patients with CF who underwent LTx were assigned to early (1999-2003), mid (2004-2008), and current (2009-2013) eras based on the date of the procedure as well as before and after implementation of the new lung allocation score system in 2005. RESULTS: CF was the indication for LTx in 14% (2,877) of who patients underwent LTx, a decrease from >17% in the early era to <13% in the current era (p < 0.001). In the pediatric cohort, CF was the indication for LTx in 383 (53%) patients, a proportion that also decreased across eras (early, 60%; mid, 53%; current, 47%; p = 0.009). The mean age of patients with CF undergoing LTx increased across the eras (early, 28 years +/- 10; mid. 28 years +/- 10; current, 30 years +/- 11; p < 0.001). Pre-transplant ventilator use and incidence of pan-resistant infections also increased (p < 0.001), whereas pre-transplant forced expiratory volume in 1 second and waitlist times decreased (p < 0.001) in patients with CF. Graft survival across the eras remained similar (p > 0.05) at 5.1 years overall. CONCLUSIONS: The proportion of LTx performed for CF has significantly decreased over time, a trend especially pronounced in pediatric patients. The change in pre transplant characteristics across eras indicates a trend to perform LTx in more clinically ill and older patients with CF. The overall post-LTx survival has not changed. PMID- 27373822 TI - Novel echocardiographic parameters of aortic insufficiency in continuous-flow left ventricular assist devices and clinical outcome. AB - BACKGROUND: The aim of this study was to evaluate the prognostic performance of novel echocardiographic (transthoracic echocardiography, or TTE) parameters for grading aortic insufficiency (AI) severity in patients with continuous-flow left ventricular assist devices (CF-LVADs). The development of AI after CF-LVAD implantation is common, although the clinical significance remains unclear. We previously described novel TTE parameters that outperformed traditional TTE parameters in grading AI severity in these patients. METHODS: CF-LVAD patients with varying degrees of AI (N = 57) underwent Doppler TTE of the LVAD outflow cannula. Patients had AI severity graded by the novel parameters (systolic/diastolic velocity ratio and the diastolic acceleration of the LVAD outflow cannula) and the traditional vena contracta. The prognostic performance of novel and traditional AI parameters was determined by comparing rates of congestive heart failure re-admission, need for aortic valve intervention, urgent transplantation and death (composite end-points) for each parameter. RESULTS: Grading AI severity using novel AI parameters led to reclassification of 32% of patients from trace/mild AI to moderate or greater AI (N = 18). Using traditional AI parameters, there was no difference in the occurrence of the composite end point between the moderate or greater group and the trace/mild group (1.50 vs 1.18 events/person, p = 0.46). With the novel AI parameters, there were significantly more events in the patients with moderate or greater AI compared to those with trace/mild AI (1.57 vs 0.13 events/person, p = 0.002). Novel parameters also better predicted the need for aortic valve intervention, urgent transplantation or death than traditional methods (p = 0.024 vs p = 0.343). CONCLUSIONS: In patients with CF-LVADs, traditional parameters tend to underestimate AI severity and future cardiac events. Novel AI TTE parameters are better able to discriminate AI severity and predict clinically meaningful outcomes. PMID- 27373823 TI - Influence of graft ischemic time and geographic distance between donor and recipient on survival in children after lung transplantation. AB - BACKGROUND: The optimal ischemic time in pediatric lung transplantation (LTx) is unclear, as recent studies have challenged the relevance of 6 hours as an upper limit to acceptable ischemic time. METHODS: Pediatric LTx recipients transplanted between 1987 and 2013 were identified in the United Network for Organ Sharing (UNOS) registry to compare survival according to ischemic time, which was categorized as <4 hours, 4 to 6 hours and >6 hours. RESULTS: Nine hundred thirty patients, all <18 years of age and receiving a first-time LTx from a cadaveric donor, were included in our investigation. Compared with <4 hours of ischemic time, univariate analysis showed a significant reduction in mortality hazard with 4 to 6 hours (hazard ratio [HR] = 0.640; 95% confidence interval [CI] 0.502 to 0.816; p < 0.001) but not >6 hours (HR = 0.985; 95% CI 0.755 to 1.284; p = 0.909). A multivariate Cox model confirmed the lowest mortality hazard to be 4 to 6 hours, as compared with <4 hours (HR = 0.533; 95% CI 0.376 to 0.755; p < 0.001). A prolonged ischemic time of >6 hours was associated with increased mortality hazard relative to the 4 to 6 hours (HR = 1.613; 95% CI 1.193 to 2.181; p = 0.002). Supplementary analyses examining geographic distance between donor and recipient identified no association between geographic distance and recipient mortality hazard. CONCLUSIONS: An ischemic time of 4 to 6 hours was associated with optimal long-term survival in first-time pediatric LTx recipients, whereas a very short ischemic time of <4 hours and a prolonged ischemic time >6 hours were both associated with higher mortality hazard in this population. PMID- 27373824 TI - De-novo donor-specific anti-HLA antibodies 30 days after lung transplantation are associated with a worse outcome. AB - BACKGROUND: The impact of de-novo donor-specific anti-HLA antibodies (DSA) on patient and graft survival after lung transplantation remains controversial. We analyzed DSA that developed at Day 7 and Month (M) 1, M3, M6 and M12 after lung transplantation and evaluated their impact on chronic lung allograft dysfunction (CLAD) development and survival. METHODS: One hundred thirty-four patients who underwent lung transplantation at our institution between November 2007 and August 2013 were included in this study. During the first post-transplant year, 82 (61%) patients developed de novo DSA and 52 (39%) patients did not. Three mean fluorescence intensity (MFI) intervals were used to define scores of anti-HLA antibody positivity: score 4 if MFI was 500 to 1,000; score 6 if MFI was 1,000 to 3,000; and score 8 if MFI was >=3,000. Patients' records were retrospectively reviewed. RESULTS: DSA with MFI scores of >=4 (hazard ratio [HR] 2.21, 95% confidence interval [CI] 1.08 to 4.54, p = 0.03), 6 (HR 2.63, 95% CI 1.27 to 5.20, p < 0.01) and 8 (HR 2.83, 95% CI 1.42 to 5.67, p < 0.01) at M1; female gender (HR 0.49, 95% CI 0.28 to 0.87, P = 0.01); and with post-operative extracorporeal membrane oxygenation (HR 0.09, 95% CI 0.01 to 0.28, p = 0.02) were significantly associated with CLAD. Multivariate analysis identified score 8 at M1 (HR 2.71, 95% CI 1.34 to 5.47, p < 0.01) as an independent risk factor for mortality. Overall, 1-, 3- and 5-year survival rates were 76%, 52% and 41% compared with 84%, 74% and 70% for patients with or without de-novo DSA at M1, respectively (p = 0.02). CONCLUSION: Early de-novo DSA may significantly impact long-term outcomes after lung transplantation and should therefore prompt regular screening. PMID- 27373825 TI - Combined Transarterial Embolization and Propranolol as Effective Treatment for Hepatic Hemangioma with Kasabach-Merritt Syndrome and Heart Failure in a Neonate. PMID- 27373826 TI - Dietary omega-3 but not omega-6 fatty acids down-regulate maternal dyslipidemia induced oxidative stress: A three generation study in rats. AB - BACKGROUND: Maternal nutrition modulates fetal metabolic programming and development later. Maternal dyslipidemia effects on oxidative stress (OS) in offsprings and its modulation by dietary fatty acids over generations remains to be elucidated. The objective of present study was to assess the long-term (three generations) effect of omega-3 fatty acids on OS under dyslipidemia. METHODS: Weanling female Wistar rats were fed with control diet (7% lard), high fat diet (35% lard, HFL), high fat with fish oil (21% fish oil + 14% lard, HFF), high fat with canola oil (21% canola oil + 14% lard, HFC) and high fat with sunflower oil (21% sunflower oil + 14% lard, HFS). Following 60 days feeding, the female rats were mated with sexually matured males (fed normal chow diet) and continued with the above diet regimen during pregnancy and lactation. The pups after lactation were continued with their maternal diet for 60 days and subjected to mating and feeding trial as above for two generations. Serum lipid profiles, OS markers (lipid peroxidation, nitric oxide release and protein carbonyl) and antioxidant defence enzymes (catalase, SOD, glutathione peroxidase and glutathione transferase) were assessed in serum, liver and uterus of rats fed on experimental and control diets for three generations. RESULTS: Feeding HFL diet increased blood lipids, OS and lowered the antioxidant enzymes activity in serum, liver and uterus (p < 0.05). The reduction in the antioxidant enzymes in HFL group were higher in third followed by second generation compared to first generation (p < 0.05). Omega-3 fatty acids prevented the dyslipidemia induced loss of antioxidant enzyme activities in serum, liver and uterus. CONCLUSIONS: Our data show for the first time that offsprings born to dyslipidemic mothers' exhibit diminished enzymatic antioxidant defence and its progressive reduction in future generation, and dietary omega-3 fatty acids restore the enzymatic antioxidant defence in offsprings and suppress the markers of OS. PMID- 27373827 TI - Interaction of serologically defined colon cancer antigen-3 with Arf6 and its predominant expression in the mouse testis. AB - ADP ribosylation factor 6 (Arf6) is a small GTPase that regulates endosomal trafficking and actin cytoskeleton remodeling. Here, we identified the serologically defined colon antigen-3 (SDCCAG3) as an Arf6-interacting protein by yeast two-hybrid screening with a constitutively active Arf6 mutant. SDCCAG3 interacts specifically with Arf6 among the Arf family members through its 101 C terminal amino acids. SDCCAG3 is expressed most intensely in the testis at the mRNA and protein levels. In the testis, SDCCAG3 is expressed in spermatocytes and spermatids. We also show that full-length SDCCAG3, but not a mutant lacking the ability to interact with Arf6, is recruited to the midbody during cytokinesis when expressed exogenously in HeLa cells. These findings suggest that SDCCAG3 might function in endosomal trafficking downstream of Arf6. PMID- 27373828 TI - 4-Phenylbutyric acid reduces mutant-TGFBIp levels and ER stress through activation of ERAD pathway in corneal fibroblasts of granular corneal dystrophy type 2. AB - Granular corneal dystrophy type 2 (GCD2) is caused by a point mutation (R124H) in the transforming growth factor beta-induced (TGFBI) gene. In GCD2 corneal fibroblasts, secretion of the accumulated mutant TGFBI-encoded protein (TGFBIp) is delayed via the endoplasmic reticulum (ER)/Golgi-dependent secretory pathway. However, ER stress as the pathogenic mechanism underlying GCD2 has not been fully characterized. The aim of this study was to confirm whether ER stress is linked to GCD2 pathogenesis and whether the chemical chaperone, 4-phenylbutyric acid (4 PBA), could be exploited as a therapy for GCD2. We found that the ER chaperone binding immunoglobulin protein (BiP) and the protein disulfide isomerase (PDI) were elevated in GCD2. Western bolt analysis also showed a significant increase in both the protein levels and the phosphorylation of the key ER stress kinases, inositol-requiring enzyme 1alpha (IRE1alpha) and double stranded RNA activated protein kinase (PKR)-like ER kinase, as well as in levels of their downstream targets, X box-binding protein 1 (XBP1) and activating transcription factor 4, respectively, in GCD2 corneal fibroblasts. GCD2 cells were found to be more susceptible to ER stress-induced cell death than were wild-type corneal fibroblasts. Treatment with 4-PBA considerably reduced the levels of BiP, IRE1alpha, and XBP1 in GCD2 cells; notably, 4-PBA treatment significantly reduced the levels of TGFBIp without change in TGFBI mRNA levels. In addition, TGFBIp levels were significantly reduced under ER stress and this reduction was considerably suppressed by the ubiquitin proteasome inhibitor MG132, indicating TGFBIp degradation via the ER-associated degradation pathway. Treatment with 4 PBA not only protected against the GCD2 cell death induced by ER stress but also significantly suppressed the MG132-mediated increase in TGFBIp levels under ER stress. Together, these results suggest that ER stress might comprise an important factor in GCD2 pathophysiology and that the effects of 4-PBA treatment might have important implications for the development of GCD2 therapeutics. PMID- 27373829 TI - EGFR and KRAS mutational analysis in a large series of Italian non-small cell lung cancer patients: 2,387 cases from a single center. AB - Activating EGFR mutations are important genetic alterations that have strong therapeutic implications for non-small cell lung cancer (NSCLC) patients. However, the role of KRAS mutations in this process is still under evaluation. Here, we report on the feasibility of a large-scale EGFR and KRAS mutation analysis in the daily routine of a single center. NSCLCs from 2,387 patients were screened for EGFR and KRAS mutations from January 2010 to September 2015. Mutational analyses were performed in a single laboratory using single strand conformation polymorphism (SSCP)-Sanger sequencing and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) on Sequenom platform for EGFR and pyrosequencing for KRAS. Activating EGFR mutations were found in 14.1% of all tumors, whereas KRAS mutations were found in 30.5% of all tumors. Direct sequencing showed analyzable cytological, small biopsy and surgical specimen percentages of 90.3, 90.9 and 98.1%, respectively, whereas the MALDI-TOF platform showed analyzable cytological samples, small biopsies and surgical specimens percentages of 94.6, 95.7 and 96.9%, respectively. The mean analytical turnaround times (TAT) were 4 and 3 days for direct sequencing and the MALDI-TOF platform, respectively. Our results confirm that small biopsy or cytological samples can be used for reliable EGFR and KRAS mutation testing and indicate that adopting the MALDI-TOF platform reduces the rate of missed samples among the samples. Moreover, the 3-day analytical TAT of the MALDI-TOF multi-target technique is appropriate for clinical management and reduces the overall treatment decision time. PMID- 27373830 TI - Spontaneous Synaptic Activation of Muscarinic Receptors by Striatal Cholinergic Neuron Firing. AB - Cholinergic interneurons (CHIs) play a major role in motor and learning functions of the striatum. As acetylcholine does not directly evoke postsynaptic events at most striatal synapses, it remains unclear how postsynaptic cholinergic receptors encode the firing patterns of CHIs in the striatum. To examine the dynamics of acetylcholine release, we used optogenetics and paired recordings from CHIs and medium spiny neurons (MSNs) virally overexpressing G-protein-activated inwardly rectifying potassium (GIRK) channels. Due to the efficient coupling between endogenous muscarinic receptors and GIRK channels, we found that firing of individual CHIs resulted in monosynaptic spontaneous inhibitory post-synaptic currents (IPSCs) in MSNs. Paired CHI-MSN recordings revealed that the high probability of acetylcholine release at these synapses allowed muscarinic receptors to faithfully encode physiological activity patterns from individual CHIs without failure. These results indicate that muscarinic receptors in striatal output neurons reliably decode CHI firing. PMID- 27373831 TI - Histone Methylation by the Kleefstra Syndrome Protein EHMT1 Mediates Homeostatic Synaptic Scaling. AB - Homeostatic plasticity, a form of synaptic plasticity, maintains the fine balance between overall excitation and inhibition in developing and mature neuronal networks. Although the synaptic mechanisms of homeostatic plasticity are well characterized, the associated transcriptional program remains poorly understood. We show that the Kleefstra-syndrome-associated protein EHMT1 plays a critical and cell-autonomous role in synaptic scaling by responding to attenuated neuronal firing or sensory drive. Chronic activity deprivation increased the amount of neuronal dimethylated H3 at lysine 9 (H3K9me2), the catalytic product of EHMT1 and an epigenetic marker for gene repression. Genetic knockdown and pharmacological blockade of EHMT1 or EHMT2 prevented the increase of H3K9me2 and synaptic scaling up. Furthermore, BDNF repression was preceded by EHMT1/2 mediated H3K9me2 deposition at the Bdnf promoter during synaptic scaling up, both in vitro and in vivo. Our findings suggest that H3K9me2-mediated changes in chromatin structure govern a repressive program that controls synaptic scaling. PMID- 27373832 TI - SRGAP2 and Its Human-Specific Paralog Co-Regulate the Development of Excitatory and Inhibitory Synapses. AB - The proper function of neural circuits requires spatially and temporally balanced development of excitatory and inhibitory synapses. However, the molecular mechanisms coordinating excitatory and inhibitory synaptogenesis remain unknown. Here we demonstrate that SRGAP2A and its human-specific paralog SRGAP2C co regulate the development of excitatory and inhibitory synapses in cortical pyramidal neurons in vivo. SRGAP2A promotes synaptic maturation, and ultimately the synaptic accumulation of AMPA and GABAA receptors, by interacting with key components of both excitatory and inhibitory postsynaptic scaffolds, Homer and Gephyrin. Furthermore, SRGAP2A limits the density of both types of synapses via its Rac1-GAP activity. SRGAP2C inhibits all identified functions of SRGAP2A, protracting the maturation and increasing the density of excitatory and inhibitory synapses. Our results uncover a molecular mechanism coordinating critical features of synaptic development and suggest that human-specific duplication of SRGAP2 might have contributed to the emergence of unique traits of human neurons while preserving the excitation/inhibition balance. PMID- 27373833 TI - Persistent Structural Plasticity Optimizes Sensory Information Processing in the Olfactory Bulb. AB - In the mammalian brain, the anatomical structure of neural circuits changes little during adulthood. As a result, adult learning and memory are thought to result from specific changes in synaptic strength. A possible exception is the olfactory bulb (OB), where activity guides interneuron turnover throughout adulthood. These adult-born granule cell (GC) interneurons form new GABAergic synapses that have little synaptic strength plasticity. In the face of persistent neuronal and synaptic turnover, how does the OB balance flexibility, as is required for adapting to changing sensory environments, with perceptual stability? Here we show that high dendritic spine turnover is a universal feature of GCs, regardless of their developmental origin and age. We find matching dynamics among postsynaptic sites on the principal neurons receiving the new synaptic inputs. We further demonstrate in silico that this coordinated structural plasticity is consistent with stable, yet flexible, decorrelated sensory representations. Together, our study reveals that persistent, coordinated synaptic structural plasticity between interneurons and principal neurons is a major mode of functional plasticity in the OB. PMID- 27373834 TI - Activation of Direct and Indirect Pathway Medium Spiny Neurons Drives Distinct Brain-wide Responses. AB - A central theory of basal ganglia function is that striatal neurons expressing the D1 and D2 dopamine receptors exert opposing brain-wide influences. However, the causal influence of each population has never been measured at the whole brain scale. Here, we selectively stimulated D1 or D2 receptor-expressing neurons while visualizing whole-brain activity with fMRI. Excitation of either inhibitory population evoked robust positive BOLD signals within striatum, while downstream regions exhibited significantly different and generally opposing responses consistent with-though not easily predicted from-contemporary models of basal ganglia function. Importantly, positive and negative signals within the striatum, thalamus, GPi, and STN were all associated with increases and decreases in single unit activity, respectively. These findings provide direct evidence for the opposing influence of D1 and D2 receptor-expressing striatal neurons on brain wide circuitry and extend the interpretability of fMRI studies by defining cell type-specific contributions to the BOLD signal. PMID- 27373835 TI - Behavior Reveals Selective Summation and Max Pooling among Olfactory Processing Channels. AB - The olfactory system is divided into processing channels (glomeruli), each receiving input from a different type of olfactory receptor neuron (ORN). Here we investigated how glomeruli combine to control behavior in freely walking Drosophila. We found that optogenetically activating single ORN types typically produced attraction, although some ORN types produced repulsion. Attraction consisted largely of a behavioral program with the following rules: at fictive odor onset, flies walked upwind, and at fictive odor offset, they reversed. When certain pairs of attractive ORN types were co-activated, the level of the behavioral response resembled the sum of the component responses. However, other pairs of attractive ORN types produced a response resembling the larger component (max pooling). Although activation of different ORN combinations produced different levels of behavior, the rules of the behavioral program were consistent. Our results illustrate a general method for inferring how groups of neurons work together to modulate behavioral programs. PMID- 27373837 TI - Sample size calculations in human electrophysiology (EEG and ERP) studies: A systematic review and recommendations for increased rigor. AB - There is increasing focus across scientific fields on adequate sample sizes to ensure non-biased and reproducible effects. Very few studies, however, report sample size calculations or even the information needed to accurately calculate sample sizes for grants and future research. We systematically reviewed 100 randomly selected clinical human electrophysiology studies from six high impact journals that frequently publish electroencephalography (EEG) and event-related potential (ERP) research to determine the proportion of studies that reported sample size calculations, as well as the proportion of studies reporting the necessary components to complete such calculations. Studies were coded by the two authors blinded to the other's results. Inter-rater reliability was 100% for the sample size calculations and kappa above 0.82 for all other variables. Zero of the 100 studies (0%) reported sample size calculations. 77% utilized repeated measures designs, yet zero studies (0%) reported the necessary variances and correlations among repeated measures to accurately calculate future sample sizes. Most studies (93%) reported study statistical values (e.g., F or t values). Only 40% reported effect sizes, 56% reported mean values, and 47% reported indices of variance (e.g., standard deviations/standard errors). Absence of such information hinders accurate determination of sample sizes for study design, grant applications, and meta-analyses of research and whether studies were adequately powered to detect effects of interest. Increased focus on sample size calculations, utilization of registered reports, and presenting information detailing sample size calculations and statistics for future researchers are needed and will increase sample size-related scientific rigor in human electrophysiology research. PMID- 27373836 TI - NBLAST: Rapid, Sensitive Comparison of Neuronal Structure and Construction of Neuron Family Databases. AB - Neural circuit mapping is generating datasets of tens of thousands of labeled neurons. New computational tools are needed to search and organize these data. We present NBLAST, a sensitive and rapid algorithm, for measuring pairwise neuronal similarity. NBLAST considers both position and local geometry, decomposing neurons into short segments; matched segments are scored using a probabilistic scoring matrix defined by statistics of matches and non-matches. We validated NBLAST on a published dataset of 16,129 single Drosophila neurons. NBLAST can distinguish neuronal types down to the finest level (single identified neurons) without a priori information. Cluster analysis of extensively studied neuronal classes identified new types and unreported topographical features. Fully automated clustering organized the validation dataset into 1,052 clusters, many of which map onto previously described neuronal types. NBLAST supports additional query types, including searching neurons against transgene expression patterns. Finally, we show that NBLAST is effective with data from other invertebrates and zebrafish. VIDEO ABSTRACT. PMID- 27373838 TI - Structural and Physicochemical Studies of Olopatadine Hydrochloride Conformational Polymorphs. AB - Crystal and molecular structures of 2 conformational polymorphs (forms I and II) of olopatadine hydrochloride, an antiallergic agent, are presented. Both crystal modifications crystallize in the monoclinic crystal system with 1 olopatadine hydrochloride molecule in the Z configuration in the asymmetric unit. Molecules are arranged into the centrosymmetric association through the interactions of the intermolecular strong and weak hydrogen bonds of N-H...Cl, O-H...Cl and C-H...Cl, C-H...O types. Conformational change between polymorphs is proved by calculations of a maximum torsion angle deviation (max[Deltatheta]) and a root-mean-square deviation between the atomic positions (rmsd[r]). The physicochemical characterization of polymorphs is performed by X-ray powder diffraction, infrared and Raman spectroscopy, differential scanning calorimetry. The comparison of the melting points and heats of fusions shows that the forms are monotropically related. PMID- 27373839 TI - Trimerization Dictates Solution Opalescence of a Monoclonal Antibody. AB - Opalescence, sometimes observed in antibody solutions, is thought to be mediated by light scattering of soluble oligomers or insoluble particulates. However, mechanistic features, such as stoichiometry and self-association affinity of oligomeric species related to opalescence, are poorly understood. Here, opalescence behavior of a monoclonal antibody (mAb-1) solution was studied over a wide range of solution conditions including different protein concentrations, pH, and in the presence or absence of salt. Hydrodynamic and thermodynamic properties of mAb-1 solutions were studied by analytical ultracentrifugation and dynamic light scattering. Opalescence in mAb-1 solutions is pH and concentration dependent. The degree of opalescence correlates with reversible monomer-trimer equilibrium detected by analytical ultracentrifugation. Increased trimer formation corresponds to increased opalescence in mAb-1 solutions at higher pH and protein concentrations. Addition of NaCl shifts this equilibrium toward monomer and reduces solution opalescence. This study demonstrates that opalescence in mAb-1 solutions does not arise from the light scattering of monomer or random molecular self-associations but is strongly correlated with a specific self-association stoichiometry and affinity. Importantly, at pH 5.5 (far below isoelectric point of mAb-1), the solution is not opalescent and with nonideal behavior. This study also dissects several parameters to describe the hydrodynamic and thermodynamic nonideality. PMID- 27373841 TI - Should We Perform the Intraoperative Sentinel Lymph Node Biopsy in Breast Cancer? AB - INTRODUCTION: The purpose of this study was to evaluate the utility of performing a selective intraoperative sentinel lymph node biopsy (SLNB) in breast cancer patients. PATIENTS AND METHODS: Patients in this prospective study were women with breast cancer seen at our hospital in 2014. These patients were divided into 2 groups on the basis of the clinical criteria age, tumor size, and molecular subtype: (1) Group A: women with clinical criteria indicative of the need to perform an intraoperative analysis of the sentinel lymph node (SLN); and (2) Group B: women in whom postoperative analysis of the SLN was performed. The final anatomopathologic findings obtained for the SLNs were analyzed and the sensitivity, specificity, positive predictive value, and negative predictive value of the clinical criteria used to decide between intraoperative or postoperative analysis of the SLN were estimated. RESULTS: A total of 170 patients were included: 106 in group A and 64 in group B. The number of positive SLNs was 29 (22 in group A and 7 in group B; P = .09). The sensitivity of our clinical criteria for establishing the indication to perform an axillary SLNB was 75.86% (95% confidence interval [CI], 56.05%-88.98%), the specificity was 40.43% (95% CI, 32.35%-49.03%), the positive predictive value was 20.75% (95% CI, 13.73% 29.95%), and the negative predictive value was 89.06% (95% CI, 78.16%-95.12%). CONCLUSIONS: The clinical findings used to decide whether or not to perform an SLNB exhibit low sensitivity and specificity and must therefore not be used to decide the need for an intraoperative SLNB. PMID- 27373842 TI - A novel arrangement of midgut epithelium and hepatic cells implies a novel regulation of the insulin signaling pathway in long-lived millipedes. AB - Nutrients absorbed by the epithelial cells of the millipede midgut are channeled to a contiguous population of hepatic cells where sugars are stored as glycogen. In insects and other arthropods, however, nutrients absorbed by midgut epithelia are first passed across the epithelial basal surface to the hemolymph before storage in fat body. The inter-digitation of cellular processes at the interface of hepatic and midgut epithelial cells offers a vast surface area for exchange of nutrients. At this interface, numerous small vesicles with the dimensions of exosomes (~30nm) may represent the mediators of nutrient exchange. Longevity and the developmental arrest of diapause are associated with reduced insulin signaling. The long lifespans for which millipedes are known may be attributable to a novel pathway with reduced insulin signaling represented by the novel arrangement of hepatic storage cells and midgut epithelial absorbing cells. PMID- 27373840 TI - The vaginal microbiota, host defence and reproductive physiology. AB - The interaction between the human host and the vaginal microbiota is highly dynamic. Major changes in the vaginal physiology and microbiota over a woman's lifetime are largely shaped by transitional periods such as puberty, menopause and pregnancy, while daily fluctuations in microbial composition observed through culture-independent studies are more likely to be the results of daily life activities and behaviours. The vaginal microbiota of reproductive-aged women is largely made up of at least five different community state types. Four of these community state types are dominated by lactic-acid producing Lactobacillus spp. while the fifth is commonly composed of anaerobes and strict anaerobes and is sometimes associated with vaginal symptoms. The production of lactic acid has been associated with contributing to the overall health of the vagina due to its direct and indirect effects on pathogens and host defence. Some species associated with non-Lactobacillus vaginal microbiota may trigger immune responses as well as degrade the host mucosa, processes that ultimately increase susceptibility to infections and contribute to negative reproductive outcomes such as infertility and preterm birth. Further studies are needed to better understand the functional underpinnings of how the vaginal microbiota affect host physiology but also how host physiology affects the vaginal microbiota. Understanding this fine-tuned interaction is key to maintaining women's reproductive health. PMID- 27373843 TI - Co-administration of cannabidiol and capsazepine reduces L-DOPA-induced dyskinesia in mice: Possible mechanism of action. PMID- 27373844 TI - Membrane topology of human monoacylglycerol acyltransferase-2 and identification of regions important for its localization to the endoplasmic reticulum. AB - Acyl CoA:2-monoacylglycerol acyltransferase (MGAT)-2 has an important role in dietary fat absorption in the intestine. MGAT2 resides in the endoplasmic reticulum and catalyzes the synthesis of diacylglycerol which is then utilized as a substrate for triacylglycerol synthesis. This triacylglycerol is then incorporated into chylomicrons which are released into the circulation. In this study, we determined the membrane topology of human MGAT2. Protease protection experiments showed that the C-terminus is exposed to the cytosol, while the N terminus is partially buried in the ER membrane. MGAT2, like murine DGAT2, was found to have two transmembrane domains. We also identified a region of MGAT2 associated with the ER membrane that contains the histidine-proline-histidine glycine sequence present in all DGAT2 family members that is thought to comprise the active site. Proteolysis experiments demonstrated that digestion of total cellular membranes from cells expressing MGAT2 with trypsin abolished MGAT activity, indicating that domains that are important for catalysis face the cytosol. We also explored the role that the five cysteines residues present in MGAT2 have in catalysis. MGAT activity was sensitive to two thiol modifiers, N ethylmaleimide and 5,5'-dithiobis-(2-nitrobenzoic acid). Furthermore, mutation of four cysteines resulted in a reduction in MGAT activity. However, when the C terminal cysteine (C334) was mutated, MGAT activity was actually higher than that of wild-type FL-MGAT2. Lastly, we determined that both transmembrane domains of MGAT2 are important for its ER localization, and that MGAT2 is present in mitochondrial-associated membranes. PMID- 27373845 TI - Anal Canal Adenocarcinoma in a Patient with Longstanding Crohn's Disease Arising From Rectal Mucosa that Migrated From a Previously Treated Rectovaginal Fistula. AB - BACKGROUND This study reports the pathogenesis of anal canal adenocarcinoma in a patient with longstanding Crohn's disease (CD). CASE REPORT A 50-year-old woman with a 33-year history of CD presented with perianal pain of several months' duration. She had been treated surgically for a rectovaginal fistula 26 years earlier and had been treated with infliximab (IFX) for the previous 4 years. A biopsy under anesthesia revealed an anal canal adenocarcinoma, which was removed by abdominoperineal resection. Pathological examination showed that a large part of the tumor consisted of mucinous adenocarcinoma at the same location as the rectovaginal fistula had been removed 26 years earlier. There was no evidence of recurrent rectovaginal fistula, but thick fibers surrounded the tumor, likely representing part of the previous rectovaginal fistula. Immunohistochemical analysis using antibodies against cytokeratins (CK20 and CK7) revealed that the adenocarcinoma arose from the rectal mucosa, not the anal glands. CONCLUSIONS Mucinous adenocarcinoma can arise in patients with CD, even in the absence of longstanding perianal disease, and may be associated with adenomatous transformation of the epithelial lining in a former fistula tract. PMID- 27373846 TI - Time-dependent impact of glutamatergic modulators on the promnesiant effect of 5 HT6R blockade on mice recognition memory. AB - Selective antagonists at serotonin 5-HT6 receptors (5-HT6R) improve memory performance in rodents and are currently under clinical investigations. If blockade of 5-HT6R is known to increase glutamate release, only two studies have so far demonstrated an interaction between 5-HT6R and glutamate transmission, but both, using the non-competitive NMDA antagonist MK-801, insensitive to variations of glutamate concentrations. In a place recognition task, we investigated here in mice the role of glutamate transmission in the beneficial effects of 5-HT6R blockade (SB-271046). Through the use of increasing intervals (2, 4 and 6h) between acquisition and retrieval, we investigated the time-dependent impact of two different glutamatergic modulators. NMDAR-dependant glutamate transmission (NMDA Receptors) was either blocked by the competitive antagonist at NMDAR, CGS 19755, or potentiated by the glycine transporter type 1 (GlyT1) inhibitor, NFPS. Results showed that neither SB-271046, nor CGS 19755, nor NFPS, alter behavioural performances after short intervals, i.e. when control mice displayed significant memory performances (2h and 4h) (respectively 10, 3, and 0.625mg.kg-1). Conversely, with the 6h-interval, a situation in which spontaneous forgetting is observed in control mice, SB-271046 improved recognition memory performances. This beneficial effect was prevented when co-administered with either CGS 19755 or NFPS, which themselves had no effect. Interestingly, a dose-dependent effect was observed with NFPS, with promnesic effect observed at lower dose (0.156mg.kg 1) when administrated alone, whereas it did no modify promnesic effect of SB 271046. These results demonstrate that promnesiant effect induced by 5-HT6R blockade is sensitive to the competitive blockade of NMDAR and underline the need of a fine adjustment of the inhibition of GlyT1. Overall, our findings support the idea of a complex crosstalk between serotonergic and glutamatergic systems in the promnesic properties of 5-HT6R antagonists. PMID- 27373847 TI - Association of serum 25-hydroxyvitamin D and serum total cholesterol with depressive symptoms in Korean adults: the Fifth Korean National Health and Nutrition Examination Survey (KNHANES V, 2010-2012). AB - OBJECTIVE: To examine the hypothesis that the association between vitamin D deficiency and depressive symptoms is dependent upon total cholesterol level in a representative national sample of the South Korean population. DESIGN: This was a population-based cross-sectional study. SETTING: The Fifth Korean National Health and Nutrition Examination Survey (KNHANES V, 2010-2012). SUBJECTS: We included 7198 adults aged 20-88 years. RESULTS: The incidence of depressive symptoms in individuals with vitamin D deficiency (serum 25-hydroxyvitamin D<20 ng/ml) was 1.54-fold (95 % CI 1.20, 1.98) greater than in individuals without vitamin D deficiency (serum 25-hydroxyvitamin D >=20 ng/ml). The relationship was stronger in individuals with normal-to-borderline serum total cholesterol (serum total cholesterol<240 mg/dl; OR=1.60; 95 % CI 1.23, 2.08) and non-significant in individuals with high serum total cholesterol (OR=0.97; 95 % CI 0.52, 1.81) after adjustment for confounding variables (age, sex, BMI, alcohol consumption, smoking status, regular exercise, income level, education level, marital status, changes in body weight, perceived body shape, season of examination date and cholesterol profiles). CONCLUSIONS: The association between vitamin D deficiency and depressive symptoms was weakened by high serum total cholesterol status. These findings suggest that both vitamin D and total cholesterol are important targets for the prevention and treatment of depression. PMID- 27373848 TI - Donepezil, an acetylcholinesterase inhibitor, attenuates LPS-induced inflammatory response in murine macrophage cell line RAW 264.7 through inhibition of nuclear factor kappa B translocation. AB - We have previously demonstrated that the pharmacotherapy with donepezil, an acetylcholinesterase inhibitor, suppresses cardiac remodeling in a mouse model of ischemic heart failure after myocardial infarction (MI). However, the precise mechanisms of the cardioprotective effect of donepezil have not been completely delineated. Because post-ischemic inflammation is a pathological key event in the cardiac remodeling process following MI, we investigated the hypothesis that donepezil acts as an inhibitor of inflammatory mediators. RAW 264.7 murine macrophage cells were pretreated with donepezil (100uM) prior to a pro inflammatory stimulation by administration of lipopolysaccharide (LPS, 10ng/ml). Donepezil significantly reduced intra- and extracellular levels of various kinds of inflammatory mediators such as TNF-alpha, IL-1beta, IL-2, IL-6 and IL-18 after the LPS stimulation, and attenuated LPS-induced nuclear translocation of nuclear factor-kappa B (NF-kappaB). These results indicate that donepezil possesses an anti-inflammatory property. However, the inhibitory effect of donepezil on the macrophage inflammatory responses was never reproduced by ACh, nor was disrupted by ACh receptor blockers. Moreover, other kinds of acetylcholinesterase inhibitors failed to inhibit the inflammatory responses in LPS-stimulated macrophage cells. These results suggest that a cholinergic anti-inflammatory pathway would not be involved in the anti-inflammatory effect of donepezil and that the specific characteristics of donepezil in suppressing the LPS-induced cytokine release and the NF-kappaB activation would be independent of its acetylcholinesterase inhibition. The present study showed that donepezil exerts an anti-inflammatory effect independently of acetylcholinesterase inhibitory action, thereby donepezil may contribute to cardioprotection during cardiac remodeling process in an ischemic heart failure after MI. PMID- 27373849 TI - Block of Na(+)/Ca(2+) exchanger by SEA0400 in human right atrial preparations from patients in sinus rhythm and in atrial fibrillation. AB - The Na(+)/Ca(2+) exchanger (NCX) plays a major role in myocardial Ca(2+) homoeostasis, but is also considered to contribute to the electrical instability and contractile dysfunction in chronic atrial fibrillation (AF). Here we have investigated the effects of the selective NCX blocker SEA0400 in human right atrial cardiomyocytes from patients in sinus rhythm (SR) and AF in order to obtain electrophysiological evidence for putative antiarrhythmic activity of this new class of drugs. Action potentials were measured in right atrial trabeculae using conventional microelectrodes. Human myocytes were enzymatically isolated. Rat atrial and ventricular cardiomyocytes were used for comparison. Using perforated-patch, NCX was measured as Ni(2+)-sensitive current during ramp pulses. In ruptured-patch experiments, NCX current was activated by changing the extracellular Ca(2+) concentration from 0 to 1mM in Na(+)-free bath solution (100mM Na(+) intracellular, "Hilgemann protocol"). Although SEA0400 was effective in rat cardiomyocytes, 10uM did not influence action potentials and contractility, neither in SR nor AF. SEA0400 (10MUM) also failed to affect human atrial NCX current measured with perforated patch. With the "Hilgemann protocol" SEA0400 concentration-dependently suppressed human atrial NCX current, and its amplitude was larger in AF than in SR cardiomyocytes. Our results confirm higher NCX activity in AF than SR. SEA0400 fails to block Ni(2+)-sensitive current in human atrial cells unless unphysiological conditions are used. We speculate that block of NCX with SEA0400 depends on intracellular Na(+) concentration. PMID- 27373850 TI - A pharmacological profile of the high-affinity GluK5 kainate receptor. AB - Mouse GluK5 was expressed in Sf9 insect cells and radiolabelled with [(3)H] kainate in receptor binding assays (Kd=6.9nM). Western immunoblotting indicated an Sf9 GluK5 band doublet corresponding to the glycosylated (128kDa) and deglycosylated (111kDa) protein, which was identical to the band pattern of native rat brain GluK5. A pharmacological profile of the high-affinity kainate receptor GluK5 is described which is distinct from the profiles of other kainate receptors (GluK1-3). The 27 tested ligands generally show a preferential affinity to GluK1 over GluK5, the exceptions being: dihydrokainate, (S)-5 fluorowillardiine, (S)-glutamate and quisqualate, where the affinity is similar at GluK1 and GluK5. In contrast, quisqualate shows 40-fold higher affinity at GluK5 over GluK3 whereas (S)-1-(2'-amino-2'-caboxyethyl)thienol[3,4-d]pyrimidin 2,4-dione (NF1231), (RS)-2-amino-3-(5-tert-butyl-3-hydroxyisoxazol-4 yl)propionate (ATPA), dihydrokainate and (2S,4R)-4-methyl-glutamate (SYM2081) have higher affinity at GluK3 compared to GluK5. Since some studies have indicated that GluK5 is associated with various diseases in the central nervous system (e.g. schizophrenia, temporal lobe epilepsy, bipolar disorder), selective GluK5 ligands could have therapeutic potential. The distinct pharmacological profile of GluK5 suggests that it would be possible to design ligands with selectivity towards GluK5. PMID- 27373852 TI - Activation of PPAR-gamma inhibits PDGF-induced proliferation of mouse renal fibroblasts. AB - Recent studies have shown that activation of peroxisome proliferators activated receptor-gamma (PPAR-gamma) ameliorates renal interstitial fibrosis (RIF) in animal model. Yet, the underlying molecular mechanisms remain still largely unknown. Here, we investigated the hypothesis that activation of PPAR-gamma regulates renal remodeling by modulating proliferation of primary cultured renal fibroblasts. In our present study, platelet-derived growth factor-AA (PDGF-AA), a key isoform of PDGF superfamily as mitogen in RIF, was applied to stimulate renal fibroblasts, the selective inhibitor or sequence specific siRNA of PI3K, skp2 or PPAR-gamma was used to investigate the involvement of above molecular mediators in PDGF-AA-induced cell proliferation. Our results demonstrate that PDGF-AA induced proliferation of renal fibroblasts by activating PI3K/AKT signaling and resultant skp2 production. Pre-stimulation of cells with rosiglitazone or adenovirus carrying PPAR-gamma cDNA (AdPPAR-gamma) blocked PDGF-AA-stimulated cell proliferation, this effect was particularly coupled to PPAR-gamma inhibition of AKT phosphorylation and skp2 expression. Inhibition of PPAR-gamma by GW9662 restored the suppression of activated PPAR-gamma on phosphorylation of AKT and subsequent skp2 production. Our results indicate that activation of PI3K/AKT signaling and resultant skp2 generation mediated PDGF-induced proliferation of renal fibroblasts. Activation of PPAR-gamma inhibited cell proliferation by inhibition of AKT phosphorylation and its down-streams. PMID- 27373851 TI - Chronic beta1-adrenoceptor blockade impairs ischaemic tolerance and preconditioning in murine myocardium. AB - beta-adrenoceptor antagonists are commonly used in ischaemic heart disease (IHD) patients, yet may impair signalling and efficacy of 'cardioprotective' interventions. We assessed effects of chronic beta1-adrenoceptor antagonism on myocardial resistance to ischaemia-reperfusion (IR) injury and the ability of cardioprotective interventions [classic ischaemic preconditioning (IPC); novel sustained ligand-activated preconditioning (SLP)] to reduce IR injury in murine hearts. Young male C57Bl/6 mice were untreated or received atenolol (0.5g/l in drinking water) for 4 weeks. Subsequently, two cardioprotective stimuli were evaluated: morphine pellets implanted (to induce SLP, controls received placebo) 5 days prior to Langendorff heart perfusion, and IPC in perfused hearts (3*1.5min ischaemia/2min reperfusion). Atenolol significantly reduced in vivo heart rate. Untreated control hearts exhibited substantial left ventricular dysfunction (~50% pressure development recovery, ~20mmHg diastolic pressure rise) with significant release of lactate dehydrogenase (LDH, tissue injury indicator) after 25min ischaemia/45min reperfusion. Contractile dysfunction and elevated LDH were reduced >50% with IPC and SLP. While atenolol treatment did not modify baseline contractile function, post-ischaemic function was significantly depressed compared to untreated hearts. Atenolol pre-treatment abolished beneficial effects of IPC, whereas SLP protection was preserved. These data indicate that chronic beta1-adrenoceptor blockade can exert negative effects on functional IR tolerance and negate conventional IPC (implicating beta1-adrenoceptors in IR injury and IPC signalling). However, novel morphine-induced SLP is resistant to inhibition by beta1-adrenoceptor antagonism. PMID- 27373853 TI - Mitochondria dysfunction: A novel therapeutic target in pathological lung remodeling or bystander? AB - The renascence in mitochondrial research has fueled breakthroughs in our understanding of mitochondrial biology identifying major roles in biological processes ranging from cellular oxygen sensing and regulation of intracellular calcium levels through to initiation of apoptosis or a shift in cell phenotype. Chronic respiratory diseases are no exception to the resurgent interest in mitochondrial biology. Microscopic observations of lungs from patients with chronic respiratory diseases such as pulmonary arterial hypertension, asthma and COPD show accumulation of dysmorphic mitochondria and provide the first evidence of mitochondrial dysfunction in diseased lungs. Recent mechanistic insights have established links between mitochondrial dysfunction or aberrant biogenesis and the pathogenesis of chronic respiratory diseases through playing a causative role in structural remodeling of the lung. The aim here is to discuss the case for a mitochondrial basis of lung remodeling in patients with chronic respiratory diseases. The present article will focus on the question of whether currently available data supports mitochondrial mechanisms as a viable point of therapeutic intervention in respiratory diseases and suggestions for future avenues of research in this rapidly evolving field. PMID- 27373855 TI - Patient stratification and the unmet need in asthma. AB - Asthma is often described as an inflammatory disease of the lungs and in most patients symptomatic treatment with bronchodilators or inhaled corticosteroids is sufficient to control disease. Unfortunately there are a proportion of patients who fail to achieve control despite treatment with the best current treatment. These severe asthma patients have been considered a homogeneous group of patients that represent the unmet therapeutic need in asthma. Many novel therapies have been tested in unselected asthma patients and the effects have often been disappointing, particularly for the highly specific monoclonal antibody-based drugs such as anti-IL-13 and anti-IL-5. More recently, it has become clear that asthma is a syndrome with many different disease drivers. Clinical trials of anti IL-13 and anti-IL-5 have focused on biomarker-defined patient groups and these trials have driven the clinical progression of these drugs. Work on asthma phenotyping indicates that there is a group of asthma patients where T helper cell type 2 (Th2) cytokines and inflammation predominate and these type 2 high (T2-high) patients can be defined by biomarkers and response to therapies targeting this type of immunity, including anti-IL-5 and anti-IL-13. However, there is still a subset of T2-low patients that do not respond to these new therapies. This T2-low group will represent the new unmet medical need now that the T2-high-targeting therapies have made it to the market. This review will examine the current thinking on patient stratification in asthma and the identification of the T2-high subset. It will also look at the T2-low patients and examine what may be the drivers of disease in these patients. PMID- 27373854 TI - From bones to blood pressure, developing novel biologic approaches targeting the osteoprotegein pathway for pulmonary vascular disease. AB - Osteoprotegerin (tnfsf11b, OPG) is a soluble member of the TNF superfamily originally described as an important regulator of osteoclastogenesis almost 20years ago. OPG is a heparin-binding secreted glycoprotein that exists as a 55 62kDa monomer or a 110-120kDa disulphide-linked homodimer. Acting as a soluble decoy receptor for RANKL, OPG actively regulates RANK signalling, and thereby osteoclastogenesis. OPG has subsequently been shown to also be a decoy receptor TNF related apoptosis inducing-ligand (tnfsf10, TRAIL, Apo2L). TRAIL is a type II transmembrane protein that is widely expressed in a variety of human tissues, including the spleen, lung, and prostate. Through binding to TRAIL, OPG can inhibit TRAIL-induced apoptosis of cancer cells. More recently, OPG has been demonstrated to be secreted by, and influence, vascular smooth muscle cells phenotype particularly related to vascular calcification and pulmonary vascular remodelling. In pulmonary artery smooth muscle cell (PASMC) suppression of BMP, induction of 5-HT and IL-1 signalling have been shown to stimulate the release of OPG in vitro, which causes cell migration and proliferation. Patients with idiopathic PAH (IPAH) demonstrate increased circulating and tissue levels of OPG, and circulating serum levels predict survival. In pre-clinical models, OPG levels correlate with disease severity. Since OPG is a naturally circulating protein, we are investigating the potential of novel biologic antibody therapies to rescue PAH phenotype in disease models. Further pre-clinical and mechanistic data are forthcoming, but we believe current published data identify OPG as an exciting and novel therapeutic target in PAH. PMID- 27373857 TI - From Best Practice to Next Practice in Nutrition Education. PMID- 27373856 TI - Neuropharmacological efficacy of the traditional Japanese Kampo medicine yokukansan and its active ingredients. AB - Dementia is a progressive neurodegenerative disorder with cognitive dysfunction, and is often complicated by behavioral and psychological symptoms of dementia (BPSD) including excitement, aggression, and hallucinations. Typical and atypical antipsychotics are used for the treatment of BPSD, but induce adverse events. The traditional Japanese Kampo medicine yokukansan (YKS), which had been originated from the traditional Chinese medicine Yi-Gan-San, has been reported to improve BPSD without severe adverse effects. In the preclinical basic studies, there are over 70 research articles indicating the neuropharmacological efficacies of YKS. In this review, we first describe the neuropharmacological actions of YKS and its bioactive ingredients. Multiple potential actions for YKS were identified, which include effects on serotonergic, glutamatergic, cholinergic, dopaminergic, adrenergic, and GABAergic neurotransmissions as well as neuroprotection, anti stress effect, promotion of neuroplasticity, and anti-inflammatory effect. Geissoschizine methyl ether (GM) in Uncaria hook and 18beta-glycyrrhetinic acid (GA) in Glycyrrhiza were responsible for several pharmacological actions of YKS. Subsequently, we describe the pharmacokinetics of GM and GA in rats. These ingredients were absorbed into the blood, crossed the blood-brain barrier, and reached the brain, in rats orally administered YKS. Moreover, autoradiography showed that [(3)H]GM predominantly distributed in the frontal cortex and [(3)H]GA in the hippocampus. Thus, YKS is a versatile herbal remedy with a variety of neuropharmacological effects, and may operate as a multicomponent drug including various active ingredients. PMID- 27373858 TI - Summer is Different: What That Means for Nutrition Educators. PMID- 27373859 TI - Participant and Household Characteristics Associated With Graduation From the Expanded Food and Nutrition Education Program. AB - OBJECTIVE: To examine empirically participant and household characteristics associated with Expanded Food and Nutrition Education Program (EFNEP) graduation and to determine whether they differ across 2 counties. DESIGN: Survey of EFNEP participants from 2011 to 2012. SETTING: Expanded Food and Nutrition Education Program sites serving limited-resource families in 1 rural and 1 urban/suburban county in Washington State. PARTICIPANTS: Expanded Food and Nutrition Education Program participants (urban/suburban: n = 647; rural: n = 569). MAIN OUTCOME MEASURE: Expanded Food and Nutrition Education Program completion/graduation. ANALYSIS: Multivariate logistic regression was used to examine associations of participant (ethnicity, race, age, education, pregnancy status, and nutrition knowledge/behavior at baseline) and household (number of people in the house, place of residence, and public assistance services) characteristics with EFNEP graduation. RESULTS: Associations were moderated by county. For the urban/suburban county, participants living with more people (after controlling for the total number of adults) were more likely to graduate. For the rural county, participants living with fewer total adults (after controlling for the total number in the house) and those with better food safety practices at baseline were more likely to graduate. CONCLUSIONS AND IMPLICATIONS: This study aids in understanding which participants are more or less likely to complete EFNEP successfully, and therefore can inform strategies aimed at increasing graduation rates. PMID- 27373861 TI - Barriers and Facilitators to Improve Fruit and Vegetable Intake Among WIC Eligible Pregnant Latinas: An Application of the Health Action Process Approach Framework. AB - OBJECTIVE: Identify barriers and facilitators to improve prenatal fruit and vegetable (F&V) intake among Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)-eligible Latinas using the Health Action Process Approach framework. DESIGN: Qualitative data were collected via audiotaped in depth interviews as part of a larger study to design an intervention to increase prenatal F&V intake. SETTING: Hartford, Connecticut. PARTICIPANTS: Forty-five WIC eligible Latinas completed the study. Included women were: >= 18 years old; in 2nd or 3rd trimester; having a singleton pregnancy; overweight or obese (ie, pregravid body mass index >= 25); not on a restricted diet; nonsmokers. PHENOMENON OF INTEREST: Prenatal factors that promote and hinder F&V intake. ANALYSIS: Transcripts were independently read and coded, and a consensus was reached about emerging themes. RESULTS: Ten factors influenced prenatal F&V intake: social support, family structure, F&V access, F&V preferences, F&V knowledge, F&V health outcome expectations, self-efficacy, intentions, F&V action/coping planning strategies, and maternal health status. CONCLUSIONS AND IMPLICATIONS: Social support from family/friends emerged as the primary distal factor driving prenatal F&V intake. Interventions designed to empower pregnant Latinas to gain the access, confidence, knowledge, and strategies necessary to consume more F&Vs must consider strengthening support to achieve the desired outcome. PMID- 27373862 TI - Motives Underlying Food Choice for Children and Perception of Nutritional Information Among Low-Income Mothers in a Latin American Country. AB - OBJECTIVE: The aim of the present study was to investigate the influence of nutritional information on how low-income mothers select food for their children. DESIGN: Five focus groups, each consisting of 5-10 participants, were conducted. PARTICIPANTS: Women, older than 18 years, mothers of young children who were beneficiaries of one of the national food stamps programs in Uruguay. PHENOMENON OF INTEREST: Focus group discussions were held around motives underlying food choices for children and perception of labeling systems. ANALYSIS: Transcripts of the focus group discussions were analyzed using inductive coding. RESULTS: Forty two women, aged between 18 and 40 years, participated in 5 focus groups. Results showed that low-income mothers do not consider nutritional information when selecting food their children. Traditional nutritional labeling was perceived as complex, difficult to find, and difficult to understand. Participants stressed that they relied on the nutrition claims included on labels for assessing the healthfulness of food products. Semi-directive and directive front-of-pack labels were positively evaluated in terms of ease of interpretation. Participants preferred the traffic light system over other alternatives. CONCLUSIONS AND IMPLICATIONS: Results suggest the need to implement simplified nutritional labeling and to regulate the use of nutrition claims on products targeted at children. PMID- 27373860 TI - Parental Nutrition Knowledge Rather Than Nutrition Label Use Is Associated With Adiposity in Children. AB - OBJECTIVE: Determine how parental nutrition label use, label literacy, and nutrition knowledge may be associated with cardiovascular health in parents and their children. DESIGN AND SETTING: Cross-sectional analyses of 2006 data from the Healthy Heart Project in Montreal, Canada. PARTICIPANTS: Among community recruited families, parents were predominantly mothers (n = 127 [80%]; mean age, 45.0 years) and half of their children were female (44%; mean age, 12.5 years). MAIN OUTCOME MEASURES: Blood pressure, lipids, and weight. Nutrition label use, label literacy, and nutrition knowledge among parents were collected using existing scales. ANALYSES: Multivariable linear regression models. RESULTS: Among parents, nutrition label use was associated with lower total cholesterol (B[SE] = -.53 [.20]; P = .009), lower low-density lipoprotein (B[SE] = -.57 [.21]; P = .007), and lower total cholesterol/high-density lipoprotein cholesterol ratio (B[SE] = -.82 [.30]; P = .008) but was not associated with adiposity. Among children, greater parental nutrition knowledge was associated with lower body mass index percentiles (B[SE] = -3.6 [1.49]; P = .02), lower waist circumference (B[SE] = -1.27 [.55]; P = .02), and lower percent body fat (B[SE] = -1.28 [.47]; P = .008). Parental nutrition label use or nutrition knowledge was not associated with children's lipids. CONCLUSIONS AND IMPLICATIONS: Parents with greater nutrition label use had more favorable lipids, but children's lipids were unaffected. Children of parents with greater nutrition knowledge had lower adiposity. Further research on the correlates of label use and health is needed. PMID- 27373863 TI - Self-Perceived Eating Habits and Food Skills of Canadians. AB - OBJECTIVE: This study identified and described Canadians' self-perceived eating habits and food skills through the use of population-based data. DESIGN: Data from the Canadian Community Health Survey 2013 Rapid Response on Food Skills was used to examine the eating quality and patterns of Canadians. Data were collected from all provinces in January and February 2013. MAIN OUTCOME MEASURES: Respondent variables (sex, age, Aboriginal/immigrant status) were examined to assess differentiations between socio-demographic groupings (family structure, marital status, education, and income). ANALYSIS: Logistic regression was used to determine whether demographic variables increased the likelihood of certain responses. RESULTS: Forty-six percent of Canadians believe they have excellent/very good eating habits, with 51% categorizing their habits as good or fair. Similarly, the majority report having good food skills. Sex and age were significantly associated with food skills, with women rating their cooking skill proficiency higher than men (72% vs 55%), and older Canadians reporting higher food skill knowledge than their younger counterparts. CONCLUSIONS AND IMPLICATIONS: Results indicate that while portions of the Canadian population have adequate food skills, others are lacking, which may negatively impact their diet. Findings from this study have implications for education and health promotion programs focusing on foods skills, particularly among vulnerable target groups. PMID- 27373864 TI - A Qualitative Investigation of Parents' Perspectives About Feeding Practices With Siblings Among Racially/Ethnically and Socioeconomically Diverse Households. AB - OBJECTIVE: Little is known about parent feeding practices with siblings. Because this is a new area of research, qualitative research is needed to understand parents' perspectives about how they make decisions about feeding siblings and whether they adapt their feeding practices dependent on sibling characteristics such as weight status. The main objective of the current study was to describe parent feeding practices with siblings. DESIGN: Qualitative cross-sectional study with 88 parents with at least 2 siblings. SETTING: Parents were interviewed in their homes in Minneapolis/St Paul Minnesota. PARTICIPANTS: Parents were from racially/ethnically diverse (64% African American) and low-income households (77% earned < $35,000/y). MAIN OUTCOME MEASURE: Parents' perceptions of feeding practices with siblings. ANALYSIS: Qualitative interviews were coded using a hybrid deductive and inductive content analysis approach. RESULTS: Parents indicated that they used child food preferences, in-the-moment decisions, and planned meals when deciding how to feed siblings. Additionally, the majority of parents indicated that they managed picky eating by making 1 meal or giving some flexibility/leeway to siblings about having other food options. Furthermore, parents endorsed using different feeding practices (eg, food restriction, portion control, pressure-to-eat, opportunities for healthful eating) with siblings dependent on child weight status or age/developmental stage. CONCLUSIONS AND IMPLICATIONS: Findings from the current study may inform future research regarding how to measure parent feeding practices with siblings in the home environment and the development of interventions tailored for families with multiple children in the home. Future quantitative research is needed to confirm these qualitative findings. PMID- 27373865 TI - Use of Blended Learning to Improve Nutrition Knowledge in Third-Graders. PMID- 27373866 TI - This Way to Produce: Strategic Use of Arrows on Grocery Floors Facilitate Produce Spending Without Increasing Shopper Budgets. PMID- 27373867 TI - An audit of patient-controlled analgesia after appendicectomy in children. AB - BACKGROUND: Patient-controlled analgesia (PCA) is commonly used after appendicectomy in children. AIM: The aim of this study was to characterize the analgesic use of children prescribed PCA after appendicetomy, in order to rationalize future use of this modality. METHODS: We retrospectively audited all cases of acute appendicitis over a 4-year period in a single pediatric hospital, recording demographics, surgical approach, pathology, analgesia use, pain scores, and duration of PCA. We preplanned subgroup analyses for surgical approach, pathology, and intraoperative nonsteroidal anti-inflammatory drug (NSAID) administration. We subsequently identified a patient subgroup who were unlikely to require PCA and conducted a (2 months) prospective audit of such patients (uncomplicated appendicitis with intraoperative NSAID) having non-PCA (oral) analgesia. RESULTS: Of the 649 patients undergoing appendicectomy for acute appendicitis, 85% were prescribed an opioid PCA, 8% received an opioid infusion (younger patients), and 7% received neither PCA nor infusion. Of the 541 bolus only PCA patients, 49% had laparoscopic surgery, 36% had complicated appendicitis, and 49% received intraoperative NSAID (diclofenac). Mean (SD) duration of PCA was shorter with uncomplicated vs complicated appendicitis (21.9 +/- 10.7 vs 32.8 +/- 21.1 h, P < 0.001, difference in means [95% CI]: 10.9 [7.7 14.1]), and with intraoperative NSAID (23.2 +/- 14.4 vs 28.4 +/- 17.4 h, P < 0.001, difference in means [95% CI]: 5.2 [2.5-7.9]). There was no difference in the time to PCA cessation between laparoscopic and open approach. Morphine consumption and pain scores were lower in the early postoperative period for those patients receiving intraoperative NSAID. In the prospective audit, 44 of 69 patients had uncomplicated appendicitis. Thirty-eight of these were prescribed oral analgesia and none required any parenteral opioid or acute pain service intervention postoperatively. Parental satisfaction level was high (>90%) with oral analgesia. CONCLUSIONS: It is feasible that children with uncomplicated appendicitis given intraoperative NSAID can be successfully managed without PCA. PMID- 27373868 TI - Urinary biomarkers in childhood lupus nephritis. AB - Juvenile-onset systemic lupus erythematosus (JSLE) is a rare, severe multisystem autoimmune disease affecting the kidney (Lupus Nephritis, LN) in up to 80% of children. LN is more severe in children than adults, with potential for irreversible kidney damage requiring dialysis or transplant. Renal biopsy is currently the gold standard for diagnosing and monitoring LN, however, it is invasive and associated with complications. Urine biomarkers have been shown to be better than serum biomarkers in differentiating renal disease from other organ manifestations. Over the past decade, there have been an increasing number of studies investigating specific candidate biomarkers implicated in the pathogenesis of LN or screening for urinary biomarkers using hypothesis free methods. In this review, developments in urine biomarkers for LN will be reviewed, highlighting those that are of relevance to children and have gone through validation in independent international patient cohorts, bringing them close to clinical translation. PMID- 27373869 TI - Characterization of the outer membrane subproteome of the virulent strain Salmonella Typhimurium SL1344. AB - : Outer membrane proteins (OMPs) play an important role in the interaction of bacterial pathogens with host cells. Indeed, some OMPs from different Gram negative bacteria have been recognized as important virulence factors for host immune recognition. This scenario has led to the study of the outer membrane (OM) subproteome of pathogenic bacteria as an essential step for gaining insight into the mechanisms of pathogenesis and for the identification of virulence factors. Although progress in the characterization of the OM has recently been reported, detailed protein composition of this subcellular localization has not been clearly defined for most pathogens. Salmonella enterica serovar Typhimurium is not only a leading cause of human gastroenteritis in high-income countries but is also one of the main causes of invasive non-typhoidal salmonellosis (iNTS) in middle- and low-income countries. The incidence of non-typhoidal salmonellosis is increasing worldwide, causing millions of infections and deaths among humans each year. Regrettably, antimicrobial resistance to a broad spectrum of antibiotics is common among non-Typhi Salmonella strains. Therefore, the development of vaccines targeting this leading invasive pathogen is warranted. In the present study we have identified the OM protein profile of the virulent S. Typhimurium strain SL1344 by means of sarkosyl extraction. SIGNIFICANCE: Salmonella enterica serovar Typhimurium causes food-borne gastroenteritis around the world, but is also responsible for a more serious manifestation of the disease through a form of invasive illness, invasive non-typhoidal Salmonella (iNTS) disease, which is considered a major public health problem in low- and middle-income countries. Even though some studies have been carried out in order to characterize the outer membrane subproteome of this human pathogen, as far as we know, this is the first report in which the most indicated methodology has been used in order to extract the outer membrane proteins and to check the presence of the proteins in the SL1344 genome; indeed all the previous studies were carried out before the genome sequence was available in 2012. Outer membrane proteins are key elements for the interaction of Gram-negative bacteria with their environment - including the host - and have fundamental roles in both infection and resistance processes. Therefore, a detailed knowledge of the outer membrane composition will certainly play a key role in providing new targets to fight this pathogen in further studies. PMID- 27373870 TI - An in-depth snake venom proteopeptidome characterization: Benchmarking Bothrops jararaca. AB - : A large-scale proteomic approach was devised to advance the understanding of venom composition. Bothrops jararaca venom was fractionated by OFFGEL followed by chromatography, generating peptidic and proteic fractions. The latter was submitted to trypsin digestion. Both fractions were separately analyzed by reversed-phase nanochromatography coupled to high resolution mass spectrometry. This strategy allowed deeper and joint characterizations of the peptidome and proteome (proteopeptidome) of this venom. Our results lead to the identification of 46 protein classes (with several uniquely assigned proteins per class) comprising eight high-abundance bona fide venom components, and 38 additional classes in smaller quantities. This last category included previously described B. jararaca venom proteins, common Elapidae venom constituents (cobra venom factor and three-finger toxin), and proteins typically encountered in lysosomes, cellular membranes and blood plasma. Furthermore, this report is the most complete snake venom peptidome described so far, both in number of peptides and in variety of unique proteins that could have originated them. It is hypothesized that such diversity could enclose cryptides, whose bioactivities would contribute to envenomation in yet undetermined ways. Finally, we propose that the broad range screening of B. jararaca peptidome will facilitate the discovery of bioactive molecules, eventually leading to valuable therapeutical agents. BIOLOGICAL SIGNIFICANCE: Our proteopeptidomic strategy yielded unprecedented insights into the remarkable diversity of B. jararaca venom composition, both at the peptide and protein levels. These results bring a substantial contribution to the actual pursuit of large-scale protein-level assignment in snake venomics. The detection of typical elapidic venom components, in a Viperidae venom, reinforces our view that the use of this approach (hand-in-hand with transcriptomic and genomic data) for venom proteomic analysis, at the specimen-level, can greatly contribute for venom toxin evolution studies. Furthermore, data were generated in support of a previous hypothesis that venom gland secretory vesicles are specialized forms of lysosomes. Two testable hypotheses also emerge from the results of this work. The first is that a nucleobindin-2-derived protein could lead to prey disorientation during envenomation, aiding in its capture by the snake. The other being that the venom's peptidome might contain a population of cryptides, whose biological activities could lead to the development of new therapeutical agents. PMID- 27373871 TI - Diabetic retinopathy: Proteomic approaches to help the differential diagnosis and to understand the underlying molecular mechanisms. AB - : Diabetic retinopathy is the most common diabetic eye disease and a leading cause of blindness among patients with diabetes. The appearance and the severity of the symptoms correlate with the duration of diabetes and poor blood glucose level management. Diabetic retinopathy is also categorized as a chronic low-level inflammatory disease; the high blood glucose level promotes the accumulation of the advanced glycation end products and leads to the stimulation of monocytes and macrophages. Examination of protein level alterations in tears using state-of the art proteomics techniques have identified several proteins as possible biomarkers for the different stages of the diabetic retinopathy. Some of the differentially expressed tear proteins have a role in the barrier function of tears linking the diabetic retinopathy with another eye complication of diabetes, namely the diabetic keratopathy resulting in impaired wound healing. Understanding the molecular events leading to the eye complications caused by hyperglycemia may help the identification of novel biomarkers as well as therapeutic targets in order to improve quality of life of diabetic patients. BIOLOGICAL SIGNIFICANCE: Diabetic retinopathy (DR), the leading cause of blindness among diabetic patients can develop without any serious symptoms therefore the early detection is crucial. Because of the increasing prevalence there is a high need for improved screening methods able to diagnose DR as soon as possible. The non-invasive collection and the relatively high protein concentration make the tear fluid a good source for biomarker discovery helping the early diagnosis. In this work we have reviewed the administration of advanced proteomics techniques used in tear biomarker studies and the identified biomarkers with potential to improve the already existing screening methods for DR detection. PMID- 27373872 TI - Superstitious behavior in sport: A literature review. AB - The objective of this first literature review, in this area, is to unveil the current status of knowledge on superstition in sport. Its outcome reveals that superstitious behaviors vary with the type of sport, athletic level, as well as athletic role. In agreement with past theories, they increase with the level of challenge, as reflected by the importance of the competition, as well as with the level of uncertainty. Cultural factors, in conjunction with the education level, as well as gender, have a strong influence on superstitious behaviors in sports. Based on current thoughts, religiosity and superstition are different psychological constructs used as psychological aids by several athletes. Personality factors appear to mediate the manifestation of the behavior. Elite athletes are clearly more superstitious than non-elite athletes, An interaction between athletic skill and task-difficulty emerges to be another strong predictor of superstition in sport. It is evident that a set of complex personal and situational factors interact in the manifestation of superstitious behavior in sport that is used for the regulation of emotions in a quest for optimal performance. It is concluded that the objective benefits (i.e., success) of superstition in sport may be ascribed to the placebo effect that yields an increased sense of control and mental reassurance in unpredictable contest situations. PMID- 27373873 TI - Synthesis of Arylazide- and Diazirine-Containing CrAsH-EDT2 Photoaffinity Probes: Unfortunately, in the article. PMID- 27373874 TI - Impact of dose-response calorie reduction or supplementation of a covertly manipulated lunchtime meal on energy compensation. AB - Numerous studies have examined energy compensation following overfeeding regimes whereas much less is known about the impact of acute underfeeding on energy compensation and fewer still have compared energy reduction and addition in the same group of individuals. This study compared the effects of consuming lunches with varying energy content (7.2-fold difference) on subsequent energy intake. A total of 27 healthy males took part in this randomized, crossover study with five treatments: 163kcal (very low energy meal, VLEM), 302kcal (low energy meal, LEM), 605kcal (control), 889kcal (high energy meal, HEM), and 1176kcal (very high energy meal, VHEM) served as a noodle soup. Participants were instructed to consume a standardized breakfast in the morning and they were provided with one of the five treatments for lunch on non-consecutive test day. Test lunches were matched for palatability, sensory properties, and volume. Participants were provided with an afternoon snack and ad libitum dinner on each test day and recorded food intake for the rest of the day. Appetite ratings were measured at regular intervals. As the energy content of treatments increased, participants' hunger, desire to eat, and prospective consumption decreased significantly whereas fullness increased significantly. However, no significant difference in subsequent meal intake was found between the treatments (P=0.458): 1003kcal VLEM, 1010kcal LEM, 1011kcal control, 940kcal HEM, and 919kcal VHEM. Total daily energy intake was statistically significantly different between the treatments (P<0.001) and was varied directly with the energy content of the lunchtime meal. Despite the large difference in energy content between the treatments, participants did not compensate for the "missing calories" or "additional calories" at subsequent meals. These results suggest that covertly manipulated, equally palatable, sensory and volume matched meals have the potential to promote either positive or negative energy balance if the effects seen in this single meal study are sustained. PMID- 27373875 TI - Phytochemistry, micromorphology and bioactivities of Ajuga chamaepitys (L.) Schreb. (Lamiaceae, Ajugoideae): Two new harpagide derivatives and an unusual iridoid glycosides pattern. AB - Ajuga chamaepitys (L.) Schreb, well-known as Camaepitium or Ground Pine, is an annual herb typical of the Mediterranean area accounting several uses in the traditional medicine. In this work we have, analyzed the plant iridoid fraction together with the essential oil composition and study of the plant indumentum. Finally, we assayed the polar extracts and essential oil obtained from the aerial parts for antioxidant activity and cytotoxicity on tumor cells. The analysis of the monoterpene glycosides allowed us to isolate from roots and aerial parts and to structurally elucidate by NMR and MS the following compounds: ajugoside (1), reptoside (2), 8-O-acetylharpagide (3), harpagide (4), 5-O-beta-d-glucopyranosyl harpagide (5), asperulosidic acid (6), deacetyl asperulosidic acid (7) and 5-O beta-d-glucopyranosyl-8-O-acetylharpagide (8), among which 5 and 8 were two new natural products. Chemotaxomic relevance of these constituents was discussed. The chemical analysis of A. chamaepitys essential oil by GC-FID and GC-MS showed ethyl linoleate (13.7%), germacrene D (13.4%), kaurene (8.4%), beta-pinene (6.8%), and (E)-phytol (5.3%) as the major volatile components. The micromorphological and histochemical study showed that iridoids and essential oil are mainly produced in the type III capitates and peltate trichomes of leaves and flowers. Biological evaluations of A. chamaepitys polar extracts and essential oil showed that the former were more potent as radical scavengers than the latter. MTT assay revealed that essential oil and ethanolic extracts were moderately cytotoxic on tumor cells with IC50 of 36.88 and 59.24MUg/mL on MDA-MB 231 cell line, respectively, and IC50 of 60.48 and 64.12MUg/mL on HCT116, respectively. PMID- 27373876 TI - Life sciences today and tomorrow: emerging biotechnologies. AB - The purpose of this review is to survey current, emerging and predicted future biotechnologies which are impacting, or are likely to impact in the future on the life sciences, with a projection for the coming 20 years. This review is intended to discuss current and future technical strategies, and to explore areas of potential growth during the foreseeable future. Information technology approaches have been employed to gather and collate data. Twelve broad categories of biotechnology have been identified which are currently impacting the life sciences and will continue to do so. In some cases, technology areas are being pushed forward by the requirement to deal with contemporary questions such as the need to address the emergence of anti-microbial resistance. In other cases, the biotechnology application is made feasible by advances in allied fields in biophysics (e.g. biosensing) and biochemistry (e.g. bio-imaging). In all cases, the biotechnologies are underpinned by the rapidly advancing fields of information systems, electronic communications and the World Wide Web together with developments in computing power and the capacity to handle extensive biological data. A rationale and narrative is given for the identification of each technology as a growth area. These technologies have been categorized by major applications, and are discussed further. This review highlights: Biotechnology has far-reaching applications which impinge on every aspect of human existence. The applications of biotechnology are currently wide ranging and will become even more diverse in the future. Access to supercomputing facilities and the ability to manipulate large, complex biological datasets, will significantly enhance knowledge and biotechnological development. PMID- 27373877 TI - What is a children's hospital and does it even matter? PMID- 27373878 TI - Socioeconomic factors and penile cancer risk and mortality; a population-based study. AB - OBJECTIVE: To investigate possible associations between socioeconomic status (SES) and penile cancer risk, stage at diagnosis, and mortality. PATIENTS/SUBJECTS AND METHODS: A population-based register study including men in Sweden diagnosed with penile cancer between 2000 and 2012 (1676 men) and randomly chosen controls (9872 men). Data were retrieved from the National Penile Cancer Register (NPECR) and several other population-based healthcare and sociodemographic registers. Educational level, disposable income, marital status, and number of individuals in the household, were assessed as indicators of SES. The risk of penile cancer and penile cancer death in relation to SES were estimated using logistic regression and proportional hazards models, respectively. Cumulative cause-specific mortality (CSM) estimates by SES were calculated using the Kaplan-Meier method. RESULTS: A low educational level and low disposable income were associated with an increased risk of invasive penile cancer. Furthermore, low educational level was associated with more advanced primary tumour stage. Divorced and never married men had a generally increased risk of penile cancer and were diagnosed with more advanced primary tumour stages. However, neither educational level nor marital status was associated with lymph node or distant metastases. Also, men in single-person households had an increased risk of both non-invasive and invasive disease. In men with invasive penile cancer, there were no significant associations of indicators of SES and CSM. CONCLUSIONS: Low educational level, low disposable income, being divorced or never married, and living in a single-person household, all increase the risk of advanced stage penile cancer, but not lymph node or distant metastases. The assessed indicators of SES did not influence penile CSM. In conclusion, our findings indicates that SES influences the risk and stage of penile cancer, but not survival. PMID- 27373879 TI - Transient risk factors for acute occupational hand injuries among metal manufacturing workers: A case-crossover study in southern China. AB - BACKGROUND: Acute occupational hand injuries are a common occurrence in China's metal manufacturing industries. This study aimed to explore the transient risk factors for acute occupational hand injuries among metal manufacturing workers. METHODS: A case-crossover study was conducted from October 2013 through December 2013 in Zhongshan city, southern China. Face-to-face interviews were used to collect information on the occurrence of 12 transient risk factors during the "hazard" period (a 60-min period prior to occupational hand injury) and a "control" period (the week before the injury). RESULTS: One hundred ninety-four qualified acute occupational hand injury cases (139 male, 55 female) were enrolled in this study, with a mean age of 35.5 (standard deviation [SD] 10.4) years. The most common (64.9%) type of work was punching, and the most common injures were crushes and fractures (28.8 and 23.7%, respectively). Of these cases, 62.9% were regarded as severe or major. Among the 12 transient risk factors, 11 ones were significantly associated with acute occupational hand injuries occurring during the hazard period: "replacing sharp knives" (IRR = 14.38, 95%CI 11.43-18.08), "using malfunctioning machinery" (IRR = 30.59, 95%CI 17.84-52.48), "using different tools" (IRR = 10.96, 95%CI 4.77-25.17), "using different machines" (IRR = 5.20, 95%CI 2.25-12.00), "performing unusual work tasks" (IRR = 24.38, 95%CI 14.11-42.15), "working overtime" (IRR = 13.40, 95%CI 7.70-23.29), "performing a task with a different method" (IRR = 56.41, 95%CI 23.61-134.81), "being in a bad mood" (IRR = 108.11, 95%CI 55.10-211.11), "feeling ill" (RR = 12.27, 95%CI 4.95-30.43), "rushing" (IRR = 5.16, 95%CI 2.49-10.70), and "not wearing gloves" (IRR = 1.63, 95%CI 1.23-2.15). CONCLUSIONS: Our study suggested that multiple transient risk factors were responsible for the acute occupational hand injuries in China's metal manufacturing industries. Am. J. Ind. Med. 59:832-840, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27373881 TI - Paenibacillus segetis sp. nov., isolated from soil of a tropical rainforest. AB - A Gram-stain-positive, facultatively anaerobic, endospore-forming, irregular rod shaped bacterium, designated DB13260T, was isolated from tropical rainforest soil in Jianfengling Nature Reserve in Hainan, China. The isolate was found to grow with 0-4 % (w/v) NaCl, at 5-40 degrees C and pH 6.0-10.5, with an optimum of 0 % NaCl, 30-37 degrees C and pH 8.5-9.0, respectively. The predominant isoprenoid quinone was menaquinone 7 (MK-7), and the major fatty acids were anteiso-C15 : 0, iso-C16 : 0 and C16 : 0. The G+C content of the genomic DNA was 53.7 mol%. Analysis of the 16S rRNA gene sequence of strain DB13260T showed an affiliation of the strain with the genus Paenibacillus, sharing 98.3 % and 97.8 % 16S rRNA gene sequence similarities with the closest relatives Paenibacillus anaericanus MH21T and Paenibacillus selenii W126T, respectively. The DNA-DNA hybridization values between strain DB13260T and the two type strains were 60.4 % and 42.6 %, respectively. The combined phenotypic and DNA-DNA hybridization data supported the conclusion that strain DB13260T represents a novel species of the genus Paenibacillus, for which the name Paenibacillussegetis sp. nov. is proposed. The type strain is DB13260T (=CGMCC 1.12769T=DSM 28014T). PMID- 27373880 TI - Transferrin receptor 1: a target for antibody-mediated cancer therapy. PMID- 27373883 TI - Retinoic Acid Modulates PTGDR Promoter Activity. AB - BACKGROUND AND OBJECTIVE: Vitamin A has been linked to the development of allergic diseases although its role is not fully understood, Retinoic acid (RA), a metabolite of Vitamin A, has been previously associated with the prostaglandin pathway, and PTGDR, a receptor of PGD2, has been proposed as a candidate gene in allergy and asthma. Considering the role of PTGDR in allergy, the goal of this study was to analyze the effect of RA on the activation of the promoter region of the PTGDR gene. METHODS: A549 lung epithelial cells were transfected with 4 combinations of genetic variants of the PTGDR promoter and stimulated with all trans RA (ATRA); luciferase assays were performed using the Dual Luciferase Reporter System, and real-time quantitative polymerase chain reaction was used to measure the expression of PTGDR, CYP26A1, RARA, RARB, RARG, and RXRA in basal A549 cell cultures and after ATRA treatment. We also performed an in silico analysis. RESULTS: After ATRA treatment increased expression of CYP26A1 (12-fold) and RARB (4-fold) was detected. ATRA activated PTGDR promoter activity in transfected cells (P<.001) and RA response element sequences were identified in silico in this promoter region. CONCLUSIONS: RA modulated PTGDR promoter activity. Differential response to RA and to new treatments based on PTGDR modulation could depend on genetic background in allergic asthmatic patients. PMID- 27373882 TI - Anterograde-propagation of axonal degeneration in the visual system of wlds mice characterized by diffusion tensor imaging. AB - PURPOSE: To evaluate the feasibility of using diffusion tensor imaging (DTI) to characterize the temporospatial profile of axonal degeneration and its relation to blood-brain barrier (BBB) permeability. MATERIALS AND METHODS: Longitudinal DTI was performed in Wallerian degeneration slow (WldS) mice following retinal ischemia. In parallel, gadolinium (Gd)-enhanced T1 -weighted imaging (Gd-T1 WI) was performed to evaluate BBB permeability in white matter during axonal degeneration. To confirm the in vivo findings, immunohistochemistry using SMI-31 and myelin basic protein (MBP) was performed to examine the axons and myelin, respectively, and Evans blue was used to evaluate the permeability of the BBB. RESULTS: Reduced axial diffusivity was found in the optic nerve (ON, -15%, P = 0.0063) 1 week and optic tact (OT, -18%, P = 0.0077) 2 weeks after retinal ischemia, which were respectively associated with an 11% (P = 0.0116) and 25% (P = 0.0001) axonal loss. Increased radial diffusivity was found 1-2 weeks after the colocated decrease of axial diffusivity (35% increase, P = 0.0388 in the ON at week 2 and an 80% increase, P = 0.0015 in the OT at week 4). No significant changes were observed using Gd-T1 WI (P = 0.13-0.75), although an approximately 1 fold increase in Evans blue staining intensity was found in the injured ON and OT starting 1 week after retinal ischemia. CONCLUSION: We demonstrated the utility of DTI to characterize anterograde-propagating axonal degeneration through the ON and OT following retinal damage. Evans blue staining revealed serum albumin accumulation at injured sites, although there was no BBB leakage detectable using Gd-T1 WI. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:482-491. PMID- 27373884 TI - A quantification model for the structure of clay materials. AB - BACKGROUND: In this paper, the quantification for clay structure is explicitly explained, and the approach and goals of quantification are also discussed. The authors consider that the purpose of the quantification for clay structure is to determine some parameters that can be used to quantitatively characterize the impact of clay structure on the macro-mechanical behaviour. METHODS: According to the system theory and the law of energy conservation, a quantification model for the structure characteristics of clay materials is established and three quantitative parameters (i.e., deformation structure potential, strength structure potential and comprehensive structure potential) are proposed. And the corresponding tests are conducted. RESULTS: The experimental results show that these quantitative parameters can accurately reflect the influence of clay structure on the deformation behaviour, strength behaviour and the relative magnitude of structural influence on the above two quantitative parameters, respectively. CONCLUSIONS: These quantitative parameters have explicit mechanical meanings, and can be used to characterize the structural influences of clay on its mechanical behaviour. PMID- 27373885 TI - Preparation, structure and luminescent properties of Eu3+ doped MBPO5 (M = Ca, Sr, Ba) red phosphor for white LED. AB - MOTIVATION: A suite of MBPO5 (borophosphates-BPO):Eu3+ (M = Ca, Sr, Ba) red emitting phosphors were synthesized and their luminescent properties were studied by excitation and emission spectra. RESULTS: The energy gap of CBPO, SBPO and BBPO are 5.481, 5.498 and 5.604 eV, respectively. While, these samples showed similar total and partial densities of states. The x-ray powder diffraction (XRD) patterns indicated that the samples were simple MPBO5 phase. According to the absorption spectra, the band gap energies of CBPO:Eu3+, SBPO: Eu3+ and BBPO:Eu3+ were calculated to be 5.499, 5.516 and 5.659 eV, respectively. The spectra of all three MBPO5:Eu3+ samples were similar with main excitation and emission peaks at 394 nm and 594 nm, respectively. The concentration quenching did not appear with the increase of the concentration of Eu3+. The charge compensator can improve the emission intensity. The average decay time of CBPO:0.05Eu3+, SBPO:0.05Eu3+ and BBPO:0.05Eu3+ was 3.29, 2.54, and 3.15 ms, respectively. The above results suggested that this phosphor was qualified as red phosphor, which could be used as a near UV-based white LED. PMID- 27373886 TI - Novel method for fabrication of samples for cell testing of bioceramics in granular form. AB - BACKGROUND: Bioceramic granules are a widely studied material for regeneration of human tissues, and their biological assessment with in vitro cell cultures plays a fundamental role in the development of bioceramics. Design of samples for cell testing represents an important aspect of the biological evaluation, as it dictates how cells will interact with the biomaterial. The aim of this study was to develop samples for cell testing of bioceramic granules with a novel design that would enable direct physical contacts between cells and bioceramic and improved handling properties for efficient laboratory work. The goal was to produce a bilayered polycaprolactone-bioceramic composite with polycaprolactone serving as a bottom layer and support for a uniform and dense layer of bioceramic granules (upper layer), which would be only partly embedded and physically stabilized in the polymer with at least one face of granules still free of any polymer residues and available for direct attachment of cells. METHODS: A novel method for preparation of samples in six steps was developed. A bilayered design of samples with exposed bioceramic particles was accomplished by the application of a water-soluble alginate as a sacrificial polymer in the method protocol. Samples were analyzed with SEM/EDX and ToF-SIMS. RESULTS: Bioceramic granules had a uniform and dense morphology and were partly embedded in the polycaprolactone support. Detailed ToF-SIMS study showed that granules were clean and free of any polymer residues. CONCLUSIONS: The developed samples enable direct exposure of bioceramic granules to cells and surrounding physiological solution during cell testing, and possess improved handling characteristics. PMID- 27373887 TI - Crystal structure and luminescent properties of Sr2SiO4:Eu2+ phosphor prepared by sol-gel method. AB - MOTIVATION: A series of Eu2+ (0.0025<= * <=0.025) activated Sr2SiO4:xEu2+ (SSO:xEu2+) phosphors were synthesized via a sol-gel method. The phosphors were characterized by x-ray diffraction (XRD), scanning electron microscopy (SEM) and photoluminescence (PL) spectroscopy. The differences between alpha' and beta phase of SSO in the density of states and energy band gap were investigated. RESULTS: The energy gap of alpha'-SSO and beta-SSO are 4.489 and 4.106 eV, respectively. While, two samples showed similar total and partial densities of states. Under the excitation by the ultra violet (UV) light (365 nm), the SSO:xEu2+ phosphor exhibited a green emission band from 400 to 700 nm, which was corresponding to the transition of 5d -> 4f of Eu2+ ions. Two emission peaks at 464 and 532 nm could be obtained through Gauss fitting curves. The ratio of the blue to green emission peak decreased with the Eu2+ concentration and the peaks shifted regularly with it. The thermal quenching property was investigated and its activation energy was calculated. The results indicated that this phosphor could be a candidate of green phosphor for UV-based light-emitting diodes (LEDs). PMID- 27373888 TI - The effects of different technologies on synthesis of CuInSe2 prepared by coreduction. AB - Solution thermal method was used to synthesize CuInSe2 powders from metal chlorides and SeO2 at 160~200 degrees C. The phases of product samples were analyzed by x-ray diffraction (XRD), the size and morphology of the products were observed by JSM6380LA scanning electron microscope (SEM). The aim is to explore the best technology to obtain the pure CuInSe2 powders. Experimental results show that, CuInSe2 phase can be formed with metal chlorides by reacting for 20 h at 160 degrees C, 180 degrees C and 200 degrees C and has XRD peaks corresponding to (112), (204) and (312) crystal planes, respectively. It consists of irregular spherical grains with about 0.2~0.5 MUm in diameter, which agglomerate larger particles with average particle size about 1~3 MUm. CuInSe2 phase was formed more easily at the temperature higher than 180 degrees C and shows better crystallinity. PMID- 27373889 TI - Accelerated life assessment of coating on the radar structure components in coastal environment. AB - AIMS: This paper aimed to build an accelerated life test scheme and carry out quantitative analysis between accelerated life test in the laboratory and actual service for the coating composed of epoxy primer and polyurethane paint on structure components of some kind of radar served in the coastal environment of South China Sea. METHODS: The accelerated life test scheme was built based on the service environment and failure analysis of the coating. The quantitative analysis between accelerated life test and actual service was conducted by comparing the gloss loss, discoloration, chalking, blistering, cracking and electrochemical impedance spectroscopy of the coating. RESULTS: The main factors leading to the coating failure were ultraviolet radiation, temperature, moisture, salt fog and loads, the accelerated life test included ultraviolet radiation, damp heat, thermal shock, fatigue and salt spray. The quantitative relationship was that one cycle of the accelerated life test was equal to actual service for one year. CONCLUSIONS: It was established that one cycle of the accelerated life test was equal to actual service for one year. It provided a precise way to predict actual service life of newly developed coatings for the manufacturer. PMID- 27373891 TI - Acute kidney injury: short-term and long-term effects. AB - Acute kidney injury (AKI) is the most common cause of organ dysfunction in critically ill adults, with a single episode of AKI, regardless of stage, carrying a significant morbidity and mortality risk. Since the consensus on AKI nomenclature has been reached, data reflecting outcomes have become more apparent allowing investigation of both short- and long-term outcomes.Classically the short-term effects of AKI can be thought of as those reflecting an acute deterioration in renal function per se. However, the effects of AKI, especially with regard to distant organ function ("organ cross-talk"), are being elucidated as is the increased susceptibility to other conditions. With regards to the long term effects, the consideration that outcome is a simple binary endpoint of dialysis or not, or survival or not, is overly simplistic, with the reality being much more complex.Also discussed are currently available treatment strategies to mitigate these adverse effects, as they have the potential to improve patient outcome and provide considerable economic health savings. Moving forward, an agreement for defining renal recovery is warranted if we are to assess and extrapolate the efficacy of novel therapies. Future research should focus on targeted therapies assessed by measure of long-term outcomes. PMID- 27373890 TI - Natural (Mineral, Vegetable, Coconut, Essential) Oils and Contact Dermatitis. AB - Natural oils include mineral oil with emollient, occlusive, and humectant properties and the plant-derived essential, coconut, and other vegetable oils, composed of triglycerides that microbiota lipases hydrolyze into glycerin, a potent humectant, and fatty acids (FAs) with varying physico-chemical properties. Unsaturated FAs have high linoleic acid used for synthesis of ceramide-I linoleate, a barrier lipid, but more pro-inflammatory omega-6:-3 ratios above 10:1, and their double bonds form less occlusive palisades. VCO FAs have a low linoleic acid content but shorter and saturated FAs that form a more compact palisade, more anti-inflammatory omega-6:-3 ratio of 2:1, close to 7:1 of olive oil, which disrupts the skin barrier, otherwise useful as a penetration enhancer. Updates on the stratum corneum illustrate how this review on the contrasting actions of NOs provide information on which to avoid and which to select for barrier repair and to lower inflammation in contact dermatitis genesis. PMID- 27373892 TI - Therapeutic Targeting of the IL-6 Trans-Signaling/Mechanistic Target of Rapamycin Complex 1 Axis in Pulmonary Emphysema. AB - RATIONALE: The potent immunomodulatory cytokine IL-6 is consistently up-regulated in human lungs with emphysema and in mouse emphysema models; however, the mechanisms by which IL-6 promotes emphysema remain obscure. IL-6 signals using two distinct modes: classical signaling via its membrane-bound IL-6 receptor (IL 6R), and trans-signaling via a naturally occurring soluble IL-6R. OBJECTIVES: To identify whether IL-6 trans-signaling and/or classical signaling contribute to the pathogenesis of emphysema. METHODS: We used the gp130F/F genetic mouse model for spontaneous emphysema and cigarette smoke-induced emphysema models. Emphysema in mice was quantified by various methods including in vivo lung function and stereology, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to assess alveolar cell apoptosis. In mouse and human lung tissues, the expression level and location of IL-6 signaling-related genes and proteins were measured, and the levels of IL-6 and related proteins in sera from emphysematous mice and patients were also assessed. MEASUREMENTS AND MAIN RESULTS: Lung tissues from patients with emphysema, and from spontaneous and cigarette smoke-induced emphysema mouse models, were characterized by excessive production of soluble IL-6R. Genetic blockade of IL-6 trans-signaling in emphysema mouse models and therapy with the IL-6 trans-signaling antagonist sgp130Fc ameliorated emphysema by suppressing augmented alveolar type II cell apoptosis. Furthermore, IL-6 trans-signaling-driven emphysematous changes in the lung correlated with mechanistic target of rapamycin complex 1 hyperactivation, and treatment of emphysema mouse models with the mechanistic target of rapamycin complex 1 inhibitor rapamycin attenuated emphysematous changes. CONCLUSIONS: Collectively, our data reveal that specific targeting of IL-6 trans-signaling may represent a novel treatment strategy for emphysema. PMID- 27373894 TI - IQRray, a new method for Affymetrix microarray quality control, and the homologous organ conservation score, a new benchmark method for quality control metrics. PMID- 27373893 TI - Components of treatment delay in rheumatoid arthritis differ according to autoantibody status: validation of a single-centre observation using national audit data. AB - OBJECTIVE: To determine whether time to treatment following symptom onset differs between RA patients according to autoantibody status. METHODS: A single-centre retrospective analysis of a UK early RA inception cohort was first undertaken to identify those components of the patient journey that differed by serological subtype. Data from a UK national audit of early inflammatory arthritis patients was accessed to replicate the key finding. RESULTS: A total of 173 RA patients were diagnosed over a 31-month period, of whom 80 (46%) were ACPA/RF double seropositive (ACPA(+)/RF(+)), 53 (31%) ACPA(-)/RF(-), 17 (10%) ACPA(+)/RF(-) and 23 (13%) RF(+)/ACPA(-) Overall, ACPA(+)/RF(+) patients experienced significantly longer symptom duration before DMARD initiation. This was accounted for by delays in their presentation to primary care following symptom onset-a finding that was robustly confirmed in an independent dataset of 2192 UK early RA patients. In contrast, ACPA(-)/RF(-) patients were significantly more likely to experience delays in DMARD initiation after presenting to secondary care. CONCLUSION: Causes of treatment delays in early RA differ according to patients' autoantibody status. More insidious symptom onset and/or distinct health-seeking behaviours among ACPA(+)/RF(+) patients may contribute to late presentations in primary care, whereas ACPA(-)/RF(-) patients experience delayed diagnosis and treatment in secondary care. These observations inform the research agenda, potentially influencing the design of service delivery for early arthritis patients. PMID- 27373895 TI - Chemical Swarming: Depending on Concentration, an Amphiphilic Ruthenium Polypyridyl Complex Induces Cell Death via Two Different Mechanisms. AB - The crystal structure and in vitro cytotoxicity of the amphiphilic ruthenium complex [3](PF6 )2 are reported. Complex [3](PF6 )2 contains a Ru-S bond that is stable in the dark in cell-growing medium, but is photosensitive. Upon blue-light irradiation, complex [3](PF6 )2 releases the cholesterol-thioether ligand 2 and an aqua ruthenium complex [1](PF6 )2 . Although ligand 2 and complex [1](PF6 )2 are by themselves not cytotoxic, complex [3](PF6 )2 was unexpectedly found to be as cytotoxic as cisplatin in the dark, that is, with micromolar effective concentrations (EC50 ), against six human cancer cell lines (A375, A431, A549, MCF-7, MDA-MB-231, and U87MG). Blue-light irradiation (lambda=450 nm, 6.3 J cm( 2) ) had little influence on the cytotoxicity of [3](PF6 )2 after 6 h of incubation time, but it increased the cytotoxicity of the complex by a factor 2 after longer (24 h) incubation. Exploring the unexpected biological activity of [3](PF6 )2 in the dark elucidated an as-yet unknown bifaceted mode of action that depended on concentration, and thus, on the aggregation state of the compound. At low concentration, it acts as a monomer, inserts into the membrane, and can deliver [1](2+) inside the cell upon blue-light activation. At higher concentrations (>3-5 MUm), complex [3](PF6 )2 forms supramolecular aggregates that induce non-apoptotic cell death by permeabilizing cell membranes and extracting lipids and membrane proteins. PMID- 27373896 TI - Dietary behaviour, food and nutrient intake of women do not change during pregnancy in Southern Ethiopia. AB - Although pregnant women are required to increase food and nutrient intake to accommodate for the increased nutritional demands, information on dietary behaviour and nutrient intake is limited. This study aimed to identify the adequacy and differences in intake between pregnant and non-pregnant women in a rural community of Butajira district, Southern Ethiopia. Simple random sampling was used to recruit 159 pregnant and 164 non-pregnant women. An interactive multiple pass 24-h recall survey was used to evaluate the food and nutrient intake of the study participants. Except for iron, vitamin A and C, intakes of macro and micronutrient were below the recommendations. Almost all study participants were deficient in energy, protein, calcium, folate and niacin intakes. There was no significant difference in the mean dietary intake of all nutrients between pregnant and non-pregnant women (p > 0.05). The prevalence of inadequacy was comparable between pregnant and non-pregnant women in all of the nutrient intakes except for Zn, where the prevalence of inadequacy was much higher among the pregnant women. Nearly all (99.0%) of the pregnant women were deficient in niacin, folate and calcium. Although all pregnant women considered it important to increase food intake during pregnancy, only a quarter of women reported to do so. In conclusion, pregnant women in the rural community of Butajira district do not make significant dietary intake adjustments to account for increased nutrient needs during pregnancy. In food insecure areas, such as ours, nutritional counselling complemented with supplementary feeding programmes could be key to ensure adequate dietary intake. (c) 2016 John Wiley & Sons Ltd. PMID- 27373897 TI - A guide to the selection of switchable functional groups for CO2-switchable compounds. AB - Many CO2-responsive species, including many of the CO2-switchable surfactants, solvents, solutes, gels, colloids, and surfaces, rely on the ability of CO2 to lower the pH of water. Uncharged basic groups on the CO2-responsive species are therefore converted from a neutral state to a protonated cationic state (a bicarbonate salt), which causes dramatic and useful changes to the properties of the species. However, this switching process only works correctly if a basic group of appropriate basicity has been selected. This article presents a comprehensive guide to the selection of basic groups for CO2-switchable species for use in water. The appropriate basicity, as measured by the pKaH (the pKa of the protonated compound), is a function of the concentration of the switchable species, the temperature, the pressure of CO2, the presence or absence of an organic liquid phase, and the solubility of the neutral form of the compound. PMID- 27373898 TI - A systematic analysis of the needs of people with HIV in Australia: stakeholder views of the key elements for a healthy life. AB - Background: The HealthMap project is developing an intervention to reduce cardiovascular risk in people living with HIV. As part of the formative stages of the intervention design, we sought to understand the needs of people with HIV (PWHIV). Methods: Two concept-mapping workshops with PWHIV (n=10), and one with HIV care providers (n=6) were conducted. The workshop findings were consolidated into a questionnaire administered to PWHIV (n=300) and HIV care providers (n=107). Participants were asked to rate the importance of each of 81 presented needs and the degree to which it was currently being met. Results: Workshops provided insights into what PWHIV perceive they need, to live with and manage their condition, and its impact on their life; these included: (1) clinical science research and development; (2) information and support; (3) personal situation; (4) healthcare quality; (5) access to services; (6) access to services specific to ageing; and (7) social justice. Questionnaire results revealed that PWHIV considered information and support, and research and development most important. For providers, healthcare quality, clients' personal situation, and social justice were most important. In terms of unmet needs, PWHIV and providers both highlighted issues in the areas of social justice, and access to aged care services. Conclusions: PWHIV and HIV providers continue to report unmet needs in the areas of social justice and emerging concerns about access to aged care services. Services must continue to address these issues of access and equity. PMID- 27373899 TI - Age of human papillomavirus vaccination? PMID- 27373901 TI - Gradient pre-emphasis to counteract first-order concomitant fields on asymmetric MRI gradient systems. AB - PURPOSE: To develop a gradient pre-emphasis scheme that prospectively counteracts the effects of the first-order concomitant fields for any arbitrary gradient waveform played on asymmetric gradient systems, and to demonstrate the effectiveness of this approach using a real-time implementation on a compact gradient system. METHODS: After reviewing the first-order concomitant fields that are present on asymmetric gradients, we developed a generalized gradient pre emphasis model assuming arbitrary gradient waveforms to counteract their effects. A numerically straightforward, easily implemented approximate solution to this pre-emphasis problem was derived that was compatible with the current hardware infrastructure of conventional MRI scanners for eddy current compensation. The proposed method was implemented on the gradient driver subsystem, and its real time use was tested using a series of phantom and in vivo data acquired from two dimensional Cartesian phase-difference, echo-planar imaging, and spiral acquisitions. RESULTS: The phantom and in vivo results demonstrated that unless accounted for, first-order concomitant fields introduce considerable phase estimation error into the measured data and result in images with spatially dependent blurring/distortion. The resulting artifacts were effectively prevented using the proposed gradient pre-emphasis. CONCLUSION: We have developed an efficient and effective gradient pre-emphasis framework to counteract the effects of first-order concomitant fields of asymmetric gradient systems. Magn Reson Med 77:2250-2262, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27373900 TI - Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04 adjuvanted vaccine in women older than 25 years: 7-year follow-up of the phase 3, double-blind, randomised controlled VIVIANE study. AB - BACKGROUND: Although the risk of human papillomavirus (HPV) infection is greatest in young women, women older than 25 years remain at risk. We present data from the VIVIANE study of the HPV 16/18 AS04-adjuvanted vaccine in adult women after 7 years of follow-up. METHODS: In this phase 3, double-blind, randomised controlled trial, healthy women older than 25 years were enrolled (age stratified: 26-35 years, 36-45 years, and >=46 years). Up to 15% in each age stratum had a history of HPV infection or disease. Women were randomly assigned (1:1) to receive HPV 16/18 vaccine or aluminium hydroxide control, with an internet-based system. The primary endpoint was vaccine efficacy against 6-month persistent infection or cervical intraepithelial neoplasia grade 1 or greater (CIN1+) associated with HPV 16/18. We did analyses in the according-to-protocol cohort for efficacy and total vaccinated cohort. Data for the combined primary endpoint in the according-to protocol cohort for efficacy were considered significant when the lower limit of the 96.2% CI around the point estimate was greater than 30%. For all other endpoints and cohorts, data were considered significant when the lower limit of the 96.2% CI was greater than 0%. This study is registered with ClinicalTrials.gov, number NCT00294047. FINDINGS: The first participant was enrolled on Feb 16, 2006, and the last study visit took place on Jan 29, 2014. 4407 women were in the according-to-protocol cohort for efficacy (n=2209 vaccine, n=2198 control) and 5747 women in the total vaccinated cohort (n=2877 vaccine, n=2870 control). At month 84, in women seronegative for the corresponding HPV type in the according-to-protocol cohort for efficacy, vaccine efficacy against 6 month persistent infection or CIN1+ associated with HPV 16/18 was significant in all age groups combined (90.5%, 96.2% CI 78.6-96.5). Vaccine efficacy against HPV 16/18-related cytological abnormalities (atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion) and CIN1+ was also significant. We also noted significant cross-protective efficacy against 6-month persistent infection with HPV 31 (65.8%, 96.2% CI 24.9-85.8) and HPV 45 (70.7%, 96.2% CI 34.2-88.4). In the total vaccinated cohort, vaccine efficacy against CIN1+ irrespective of HPV was significant (22.9%, 96.2% CI 4.8-37.7). Serious adverse events related to vaccination occurred in five (0.2%) of 2877 women in the vaccine group and eight (0.3%) of 2870 women in the control group. INTERPRETATION: In women older than 25 years, the HPV 16/18 vaccine continues to protect against infections, cytological abnormalities, and lesions associated with HPV 16/18 and CIN1+ irrespective of HPV type, and infection with non-vaccine types HPV 31 and HPV 45 over 7 years of follow-up. FUNDING: GlaxoSmithKline Biologicals SA. PMID- 27373902 TI - Field comparison of two inhalable samplers used in Italy to measure the wood dust exposure. AB - BACKGROUND: Particle size affects the performance of personal air samplers used to measure dust exposure in the workplace. Few field studies have been conducted for comparing the performance of personal inhalable samplers. OBJECTIVE: To compare wood dust sampling with two inhalable samplers: IOM (Institute of Occupational Medicine) and Italian cone. METHODS: 136 Italian cone/IOM paired samples and 136 passive IOM samples were collected in 30 Italian woodworking industries. The valid number of sample pairs was 114. Ultra-large particles were collected by passive IOM. The sampling membranes were weighed and the size particles were measured. Mass differences in active and passive IOM samples were calculated (IOM-Delta). RESULTS: Statistical analysis of all 114 Italian cone/active IOM paired results showed a significant mass difference (P < 0.05) and no significant mass difference for sanding and cutting woodworking processes. The Italian cone/IOM-Delta paired results consistently showed no statistically significant mass differences in any woodworking processes. Both samplers performed similarly when ultra-large particles mass contribution was not considered. CONCLUSIONS: These findings confirm the presence of ultra-large particles in woodworking. The Italian cone and IOM samplers can be used interchangeably for personal wood dust exposure assessment, when the wood activities produce small-size particles. PMID- 27373903 TI - Maternal outcome in pregnant women with lupus nephritis. A prospective multicenter study. AB - Retrospective studies reported a high incidence of maternal complications in pregnant women with lupus. In this paper we prospectively assessed the rate of risk and the risk factors of maternal outcome in women with stable lupus nephritis who received pre-pregnancy counseling. This prospective multicenter study includes 71 pregnancies in 61 women with lupus nephritis who became pregnant between 2006 and 2013. Complete renal remission was present before pregnancy in 56 cases (78.9%) and mild active nephritis in 15 cases. All women underwent a screening visit before pregnancy and were closely monitored by a multidisciplinary team. Lupus anticoagulant, serum C3 and C4 complement fractions, anti-DNA antibodies, anti-C1q antibodies, anticardiolipin IgG and IgM antibodies, anti-beta2 IgG and IgM antibodies were tested at screening visit, at first, second, third trimester of pregnancy, and one year after delivery. Renal flares of lupus during or after pregnancy, pre-eclampsia, and HELLP syndrome were defined as adverse maternal outcomes. Fourteen flares (19.7%), six cases of pre eclampsia (8.4%) and two cases of HELLP (2.8%) occurred during the study period. All flares responded to therapy and the manifestations of pre-eclampsia and HELLP were promptly reversible. Low C3, high anti-DNA antibodies and predicted all renal flares. High anti-C1q antibodies and low C4 predicted early flares. The body mass index (BMI) was associated with increased risk of late flares. History of previous renal flares and the presence of clinically active lupus nephritis at conception did not increase the risk of renal flares during pregnancy. History of renal flares before pregnancy, arterial hypertension, and longer disease predicted pre-eclampsia/HELLP. In pregnant women with lupus nephritis adverse maternal outcomes were relatively common but proved to be reversible when promptly diagnosed and treated. Immunological activity, arterial hypertension and BMI may predispose to maternal complications. PMID- 27373904 TI - Success and failure of biological treatment in systemic lupus erythematosus: A critical analysis. AB - Patients affected with systemic lupus erythematosus (SLE) still display increased mortality and decreased quality of life in respect to general population. The major determinant of poor long term prognosis is organ damage, which is predictive of more damage and death. Damage is in turn triggered by uncontrolled disease activity and especially by the long-standing corticosteroid use which often accompanies SLE patients over their disease course, owing both to the need of reaching disease remission and to the habit of keeping patients on a small steroid dose for an indefinite period of time. Hence, the need for new drugs and therapeutic strategies aiming at minimizing damage accrual through a better control of disease activity and a steroid-sparing potential is paramount. So far, however, the therapeutic strategy in SLE requires a multitarget approach which is not devoid of widespread immunesuppression. In fact, several studies have been carried out in recent years targeting both the adaptive and the innate immune system, the majority of which did not achieve their primary endpoint, being often divergent from successful clinical experience and thereby committing physician to off-label use of targeted therapies in face of refractory SLE manifestations. The study designs and the chosen endpoints were often blamed for inadequacy, being at least in part responsible for study failures. In this review, we go over major clinical trials conducted in SLE by analyzing any critical aspects related to study design, predefined endpoints and biological activity of novel compounds that may have hampered study outcome, despite the great effort of providing less toxic drugs within a targeted, pathogenic-based approach. PMID- 27373905 TI - Highly sensitive gas-phase explosive detection by luminescent microporous polymer networks. AB - We propose microporous networks (MPNs) of a light emitting spiro-carbazole based polymer (PSpCz) as luminescent sensor for nitro-aromatic compounds. The MPNs used in this study can be easily synthesized on arbitrarily sized/shaped substrates by simple and low-cost electrochemical deposition. The resulting MPN afford an extremely high specific surface area of 1300 m(2)/g, more than three orders of magnitude higher than that of the thin films of the respective monomer. We demonstrate, that the luminescence of PSpCz is selectively quenched by nitro aromatic analytes, e.g. nitrobenzene, 2,4-DNT and TNT. In striking contrast to a control sample based on non-porous spiro-carbazole, which does not show any luminescence quenching upon exposure to TNT at levels of 3 ppm and below, the microporous PSpCz shows a clearly detectable response even at TNT concentrations as low as 5 ppb, clearly demonstrating the advantage of microporous films as luminescent sensors for traces of explosive analytes. This level states the vapor pressure of TNT at room temperature. PMID- 27373906 TI - Activation of the sigma receptor 1 modulates AMPA receptor-mediated light-evoked excitatory postsynaptic currents in rat retinal ganglion cells. AB - Sigma receptor (sigmaR), a unique receptor family, is classified into three subtypes: sigmaR1, sigmaR2 and sigmaR3. It was previously shown that sigmaR1 activation induced by 1MUM SKF10047 (SKF) suppressed N-methyl-d-aspartate (NMDA) receptor-mediated responses of rat retinal ganglion cells (GCs) and the suppression was mediated by a distinct Ca(2+)-dependent phospholipase C (PLC) protein kinase C (PKC) pathway. In the present work, using whole-cell patch-clamp techniques in rat retinal slice preparations, we further demonstrate that SKF of higher dosage (50MUM) significantly suppressed AMPA receptor (AMPAR)-mediated light-evoked excitatory postsynaptic currents (L-EPSCs) of retinal ON-type GCs (ON GCs), and the effect was reversed by the sigmaR1 antagonist BD1047, suggesting the involvement of sigmaR1. The SKF (50MUM) effect was unlikely due to a change in glutamate release from bipolar cells, as suggested by the unaltered paired-pulse ratio (PPR) of AMPAR-mediated EPSCs of ON GCs. SKF (50MUM) did not change L-EPSCs of ON GCs when the G protein inhibitor GDP-beta-S or the protein kinase G (PKG) inhibitor KT5823 was intracellularly infused. Calcium imaging further revealed that SKF (50MUM) did not change intracellular calcium concentration in GCs and persisted to suppress L-EPSCs when intracellular calcium was chelated by BAPTA. The SKF (50MUM) effect was intact when protein kinase A (PKA) and phosphatidylinostiol (PI)-PLC signaling pathways were both blocked. We conclude that the SKF (50MUM) effect is Ca(2+)-independent, PKG-dependent, but not involving PKA, PI-PLC pathways. PMID- 27373908 TI - Cooperative binding and extraction of sodium nitrite by a ditopic receptor incorporated into a polymeric resin. AB - Simple ion pair receptors were synthesised and characterized in solution. The modular design of these receptors facilitated the preparation of a functionally analogous polymeric material able to extract sodium nitrite from acetonitrile solution. PMID- 27373909 TI - Clinical response to liposomal doxorubicin and rituximab in HHV-8-associated multicentric Castleman's disease in an HIV-positive patient. AB - We report a patient with HIV-associated multicentric Castleman's disease who had recurrent human herpesvirus-8 viremia associated with intermittent febrile exanthema and lymphadenopathy. Although the patient relapsed after single-agent treatment with liposomal doxorubicin, weekly infusions of rituximab led to complete remission even though the reactivation of the Kaposi's sarcoma was unfortunately observed. Rituximab could not only eliminate the accumulation of HHV-8 load but also play a part in the modulation of dysregulated CD20-positive B cells in HIV-associated multicentric Castleman's disease. PMID- 27373907 TI - Nucleolin interacts with influenza A nucleoprotein and contributes to viral ribonucleoprotein complexes nuclear trafficking and efficient influenza viral replication. AB - Influenza viruses replicate their single-stranded RNA genomes in the nucleus of infected cells and these replicated genomes (vRNPs) are then exported from the nucleus to the cytoplasm and plasma membrane before budding. To achieve this export, influenza viruses hijack the host cell export machinery. However, the complete mechanisms underlying this hijacking remain not fully understood. We have previously shown that influenza viruses induce a marked alteration of the nucleus during the time-course of infection and notably in the nucleolar compartment. In this study, we discovered that a major nucleolar component, called nucleolin, is required for an efficient export of vRNPs and viral replication. We have notably shown that nucleolin interacts with the viral nucleoprotein (NP) that mainly constitutes vRNPs. Our results suggest that this interaction could allow vRNPs to "catch" the host cell export machinery, a necessary step for viral replication. PMID- 27373910 TI - Do refined consensus guidelines improve the uniformity of clinical target volume delineation for rectal cancer? Results of a national review project. AB - In a previous national central review project, 74% of the rectal cancer clinical target volumes (CTVs) needed a modification. In a follow-up initiative, we evaluated whether the use of refined international consensus guidelines improves the uniformity of CTV delineation in clinical practice. PMID- 27373911 TI - Changes in treatment patterns and impact of radiotherapy for early stage diffuse large B cell lymphoma after Rituximab: A population-based analysis. AB - PURPOSE: Use of Rituximab for diffuse large B cell lymphoma (DLBCL) has improved outcomes and led to further questions regarding the benefit of consolidative radiation therapy (RT). This study sought to determine changes in RT utilization following the incorporation of Rituximab for treatment of early stage DLBCL and to examine survival outcomes. MATERIALS/METHODS: We included patients in the Surveillance, Epidemiology, and End Results database, diagnosed with Stage I-II DLBCL between 1992 and 2011. Linear regression was performed to determine rate of RT utilization over time during the pre- and post-Rituximab eras (1992-2001 vs. 2002-2011). Kaplan-Meier and Cox Regression were performed to compare overall survival (OS) for patients treated with or without RT. Propensity-score matching was used to compare survival outcomes to account for indication bias. RESULTS: 34,680 patients met the specified criteria. RT utilization was 35.2% in the pre Rituximab era and 29.9% in the post-Rituximab era (P<0.001). Linear regression revealed that in the pre-Rituximab era the slope of the best fit line for RT utilization by year was positive (m=0.01, P=0.0046), while the slope was negative in the post-Rituximab era (m=-0.008, P=0.0102). RT use was associated with improved OS in both the pre-Rituximab era (hazard ratio [HR]=0.797; 95% confidence interval [CI] 0.756-0.841) and the post-Rituximab era (HR=0.745; 95% CI 0.702-0.789). Propensity-score matched analysis confirmed that RT use improved OS in the pre-Rituximab era (HR=0.844; 95% CI 0.793-0.897) and post-Rituximab era (0.754; 95% CI 0.703-0.809). CONCLUSION: RT utilization has decreased following incorporation of Rituximab for first line treatment of DLBCL. RT use is associated with improved OS in both pre- and post-Rituximab eras, suggesting that RT should continue to be used for management of early stage DLBCL, even in the era of Rituximab. PMID- 27373912 TI - Agromyces aureus sp. nov., isolated from the rhizosphere of Salix caprea L. grown in a heavy-metal-contaminated soil. AB - A Gram-reaction-positive, motile, yellow-pigmented and rod-shaped bacterial strain, designated AR33T, was isolated from the rhizosphere of Salix caprea L. growing in a former zinc/lead mining and processing site in Austria. A polyphasic approach was applied to determine its taxonomic position. 16S rRNA gene sequence analysis, and morphological and chemotaxonomic properties showed that strain AR33T belongs to the genus Agromyces. Strain AR33T had peptidoglycan type B2gamma and the major menaquinones were MK-11, MK-10 and MK-12. The main branched-chain fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. Strain AR33T showed catalase and oxidase activity and multiple heavy metal resistances to zinc, lead and cadmium. The DNA G+C content was 70.1 mol%. Levels of 16S rRNA gene sequence similarity with closely related recognized species of the genus Agromyces ranged between 98 and 99 %. However, DNA-DNA hybridization between strain AR33T and the type strains of three Agromyces species showed values lower than 42 % relatedness. Therefore, differential phenotypic characteristics together with DNA-DNA relatedness suggested that strain AR33T can be recognized as representing a distinct Agromyces species, for which the name Agromyces aureus sp. nov. is proposed. The type strain is AR33T (=DSM 101731T=LMG 29235T). PMID- 27373913 TI - Rheological Properties of a Heat-reversible Gel of Water-soluble Soybean Polysaccharide Extracted under Acidic Conditions. AB - We studied the rheological properties of a heat-reversible gel formed with water soluble soybean polysaccharides (RG-SSPS) which had been extracted from purified polysaccharides of soybean cotyledon meal at pH 2 and 80 degrees C for 90 min. It was found that the gelling point and melting point of this heat-reversible gel were at approximately 51 degrees C and 46 degrees C, respectively. Gelation was observed in aqueous solutions with a concentration of over 3%, but not at 1%, at 5 degrees C. The influence of pH on the gel strength of RG-SSPS was strong. Especially on the acidic side, the G' and G" values, which were highest at pH 7, were remarkably low and no gel was formed at pH 5. The addition of EDTA lowered the G' and G" values, while the addition of Ca raised them. These findings and the analytical results for the fractions obtained from RG-SSPS after reheating at pH 5 and 120 degrees C for 90 min, under which conditions the non-gel-forming polysaccharides were extracted, suggest that gelation was due to weak bonding and cross-linking between polyvalent cations and low-methoxyl uronic acid regions in the homogalacturonic or rhamnogalacturonic main chain of the RG-SSPS structure. The results also suggest that the heat reversibility was due to weakness of the bonding which did not conform to the egg-box model, like the mechanism for low methoxyl pectin or sodium alginate, because the neutral sugar side chains of the RG-SSPS structure are thought to limit their mutual proximity. PMID- 27373914 TI - Enzymes Responsible for Acetate Oxidation by Acetic Acid Bacteria. AB - Several acetic acid bacteria of the genus Acetobacter oxidize much acetate oxidation, which is not desired in vinegar manufacturing. Acetobacter rancens SKU 1111, a strong acetate oxidant, grew rapidly with a biphasic growth curve while consuming acetate in the second growth phase. Acetobacter aceti IFO 3284 did not show extensive acetate oxidation. Addition of glycerol to the culture medium of Acetobacter rancens SKU 1111 increased acetate oxidation and resulted in more biomass in the second growth phase than when glycerol was not added. Enzyme activities of acetyl-CoA synthetase and phosphotransacetylase in the organism were high during acetate oxidation. The activity of phosphoenolpyruvate carboxylase was most stimulated by a trace amount of acetyl-CoA among the enzymes of glycerol catabolism. Phosphoenolpyruvate carboxylase in A. rancens SKU 1111 showed a sigmoidal saturation curve with acetyl-CoA. This finding suggested that strong acetate oxidation caused by acetyl-CoA synthetase or phosphotransacetylase activity, together with phosphoenolpyruvate carboxylase, increased the biomass. PMID- 27373915 TI - Synthesis of (+/-)-Methyl Tuberonate, a Potato Tuber-forming Substance, and Its Epimer. AB - Methyl esters of (+/-)-tuberonic acid and (+/-)-12-hydroxyjasmonic acid (trans tuberonic acid), the aglycons of strong potato tuber-forming substances, were synthesized from norbornene via side-chain elongation and Baeyer-Villiger oxidation as key steps. PMID- 27373916 TI - Crystallization and Properties of NADPH-Dependent L-Sorbose Reductase from Gluconobacter melanogenus IFO 3294. AB - NADPH-Dependent L-sorbose reductase (SORD, synonimously NADP-dependent D-srobitol dehydrogenase) was purified and crystallized for the first time from the cytosolic fraction of Gluconobacter melanogenus IFO 3294. The enzyme catalyzed oxidoreduction between D-sorbitol and L-sorbose in the presence of NADP or NADPH. Affinity chromatography by a Blue-dextran Sepharose 4B column was effective for purifying the enzyme giving about 770-fold purification with an overall yield of more than 50%. The crystalline enzyme showed a single sedimentation peak in analytical ultracentrifugation, giving an apparent sedimentation constant of 3.8 s. Gel filtration on a Sephadex G-75 column gave the molecular mass of 60 kDa to the enzyme, which dissociated into 30 kDa subunit on SDS-PAGE, indicating that the enzyme is composed of 2 identical subunits. Reduction of L-sorbose to D sorbitol predominated in the presence of NADPH with the optimum pH of 5.0-7.0. Oxidation of D-sorbitol to L-sorbose was observed in the presence of NADP at the optimum pH of 7.0-9.0. The relative rate of L-sorbose reduction was more than seven times higher to that of D-sorbitol oxidation. NAD and NADH were inert for both reactions. D-Fructose reduction in the presence of NADPH did not occur with SORD. Since the reaction rate in L-sorbose reduction highly predominated over D sorbitol oxidation over a wide pH range, the enzyme could be available for direct enzymatic measurement of L-sorbose. Even in the presence of a large excess of D glucose and other substances, oxidation of NADPH to NADP was highly specific and stoichiometric to the L-sorbose reduced. Judging from the enzymatic properties, SORD would contribute to the intracellular assimilation of L-sorbose incorporated from outside the cells where L-sorbose is accumulated in huge amounts in the culture medium. PMID- 27373917 TI - Lipase-catalyzed Kinetic Resolution of (+/-)-trans- and cis-2-Azidocycloalkanols. AB - The lipase-catalyzed kinetic resolution of trans- and cis-2-azidocycloalkanols and the preparation of enantiomerically pure trans- and cis-2-aminocycloalkanols are described. Four kinds of lipases were screened for the acetylation of trans- and cis-2-azidocycloalkanols. Among them, Pseudomonas sp. lipases (lipase PS and lipase AK, Amamo Pharmaceutical Co.) showed the highest enantioselectivity. These products were converted to the corresponding 2-aminocycloalkanols to determine their enantiomeric excess (ee) and absolute configurations by HPLC and CD analyses, using (S)-TBMB carboxylic acid [(S)-2-tert-butyl-2-methyl-1,3 benzodioxole-4-carboxylic acid] as the chiral conversion reagent. The results of the CD analysis proved N,O-bis-(S)-TBMB carboxylated cis-2-aminocycloalkanols to adopt a predominantly N-equatorial conformation. The partially resolved trans- and cis-2-aminocycloalkanols, except for trans-2-aminocyclopentanol, were recrystallized from ethyl acetate to give enantiomerically pure forms. PMID- 27373918 TI - Production of D-Glutamate from L-Glutamate with Glutamate Racemase and L Glutamate Oxidase. AB - We studied production of D-glutamate from L-glutamate using a bioreactor consisting of two columns of sequentially connected immobilized glutamate racemase (EC 5.1.1.3, from Bacillus subtilis IFO 3336) and L-glutamate oxidase (EC 1.4.3.11, from Streptomyces sp. X119-6): L-glutamate was racemized by the glutamate racemase column, and then L-glutamate was oxidized by the L-glutamate oxidase column. Consequently only D-glutamate remained, and was easily separated from the alpha-ketoglutarate formed by anion-exchange chromatography. Both enzymes were highly stabilized by immobilization. The pH and temperature optima of immobilized glutamate racemase (pH 8, 40 degrees C) were similar to those of immobilized L-glutamate oxidase (pH 7, 50 degrees C). Accordingly, we connected the two columns tandemly to do both enzyme reactions under the same conditions. Actually 4.5 MUmol of D-glutamate was produced and isolated from 10 MUmol of L glutamate, about 90% of the theoretical yield. PMID- 27373919 TI - Subsite Structure of alpha-Amylase II from Thermoactinomyces vulgaris R-47. AB - We estimated the subsite structure of alpha-amylase II (TVA II) from Thermoactinomyces vulgaris R-47 expressed in Escherichia coli. TVA II has eight subsites, and the catalytic site is between the 5th and 6th subsite from the non reducing end side. The subsite affinities, A-5, A-4, A-3, A-2, (A-1+A+1), A+2, and A+3, were calculated to be -0.35, 0.93, 0.55, 2.56, 1.18, 1.71, and 0.01 kcal mol(-1), respectively. PMID- 27373920 TI - High-level Expression of a Recombinant Thermostable Phytase in Bacillus subtilis. AB - An efficient expression system was developed in Bacillus subtilis for the large scale production of phytase. The phytase gene with a native promoter derived from Bacillus amyloliquefaciens was cloned in the Bacillus expression vector pJH27 under a strong BJ27 promoter and its expression was optimized. The expression of the phytase gene occurred during late exponential growth and the extracellular phytase production was 2.0 units/ml, which constituted over 90% of the total protein. The yield was 100-fold higher than wild type Bacillus amyloliquefaciens DS11. PMID- 27373921 TI - Competing Effect of Polyols on the Thermal Stability and Gelation of Soy Protein. AB - The thermal denaturation temperature of a soy protein isolate was increased, but its gel-melting temperature was decreased by the addition of polyols with increasing concentration and number of hydroxyl groups of the polyols. This inverse stabilizing effect of polyols on the protein structure and gel is discussed in terms of the competing solvent effects on intra- and intermolecular hydrophobic interactions and on the peptide-peptide hydrogen bonds of the protein. PMID- 27373922 TI - Optical Resolution by the Replacing Crystallization of DL-Threonine with L Alanine as an Optically Active Cosolute. AB - DL-Threonine (DL-Thr) was optically resolved by replacing crystallization with L alanine (L-Ala) as an optically active cosolute. D-Thr was preferentially crystallized from a supersaturated aqueous solution of DL-Thr in the presence of L-Ala. Optical resolution was successfully achieved to afford D-Thr with an optical purity of 96-98% and L-Thr of 91-95%. The partially resolved D- and L-Thr were recrystallized from water, taking account of the solubility of DL-Thr, to efficiently yield both enantiomers in an optically pure form. PMID- 27373923 TI - Organic photoredox catalysis for the oxidation of silicates: applications in radical synthesis and dual catalysis. AB - Metal free photooxidation of alkyl bis(catecholato)silicates with the organic dye 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyano-benzene (4CzIPN) allows the smooth formation of alkyl radicals. The latter can be efficiently engaged either with radical acceptors to provide homolytic addition products or in photoredox/nickel dual catalysis reactions to obtain cross-coupling products. PMID- 27373924 TI - Self-perceived Sleep Quality and Quantity in Adults With Asthma: Findings From the CosteAsma Study. AB - BACKGROUND AND OBJECTIVE: Nocturnal asthma symptoms are associated with poor sleep quality, excessive daytime sleepiness, and poor daytime functioning. The aim of this study was to describe self-perceived sleep quality and quantity in asthmatic adults in a real-world setting according to different determinants of patient health status. METHODS: A cross-sectional, observational, seasonal, multiwave survey was designed. Allergists nationwide were asked to consecutively survey adult asthmatics aged 18 to 65 years, evenly distributed by seasons and asthma severity (Global Initiative for Asthma criteria). Sleep quality and quantity were assessed using the self-administered Medical Outcomes Study (MOS) Sleep Scale. The Asthma Control Test was applied to ascertain the degree of asthma symptom control. RESULTS: A total of 1098 individuals (58.7% females, 41.2 [13.6] years) were analyzed. Asthma severity was associated with poor sleep quality and quantity; patients with more severe disease scored higher on the MOS Sleep Scale (P<.001) and also reported significantly fewer daily average hours of sleep (0.3-0.5 hours, P<.001). Level of symptom control and asthma severity were both associated with poor sleep quality and quantity, with the following mean MOS sleep problem index scores: 25.3 (fully controlled asthma), 26.4 (controlled), 32.6 (partly controlled), and 44.6 (uncontrolled) (P<.001), and 48.4 (severe asthma), 39.0 (moderate), 32.6 (mild), and 26.5 (intermittent) (P<.001). Sex was significantly associated with the summary MOS sleep problem index. CONCLUSIONS: Sleep quality and quantity was significantly associated with poor health status in asthmatic patients. Guidelines should recommend asking about nocturnal asthma symptoms and encourage clinicians to take a global sleep history. Better control of nocturnal asthma symptoms could lead to improved sleep quality and a decrease in daytime sleep-related symptoms. PMID- 27373926 TI - Dopamine D2 Receptor-Mediated Regulation of Pancreatic beta Cell Mass. AB - Understanding the molecular mechanisms that regulate beta cell mass and proliferation is important for the treatment of diabetes. Here, we identified domperidone (DPD), a dopamine D2 receptor (DRD2) antagonist that enhances beta cell mass. Over time, islet beta cell loss occurs in dissociation cultures, and this was inhibited by DPD. DPD increased proliferation and decreased apoptosis of beta cells through increasing intracellular cAMP. DPD prevented beta cell dedifferentiation, which together highly contributed to the increased beta cell mass. DRD2 knockdown phenocopied the effects of domperidone and increased the number of beta cells. Drd2 overexpression sensitized the dopamine responsiveness of beta cells and increased apoptosis. Further analysis revealed that the adenosine agonist 5'-N-ethylcarboxamidoadenosine, a previously identified promoter of beta cell proliferation, acted with DPD to increase the number of beta cells. In humans, dopamine also modulates beta cell mass through DRD2 and exerts an inhibitory effect on adenosine signaling. PMID- 27373925 TI - Regulation of the DNA Methylation Landscape in Human Somatic Cell Reprogramming by the miR-29 Family. AB - Reprogramming to pluripotency after overexpression of OCT4, SOX2, KLF4, and MYC is accompanied by global genomic and epigenomic changes. Histone modification and DNA methylation states in induced pluripotent stem cells (iPSCs) have been shown to be highly similar to embryonic stem cells (ESCs). However, epigenetic differences still exist between iPSCs and ESCs. In particular, aberrant DNA methylation states found in iPSCs are a major concern when using iPSCs in a clinical setting. Thus, it is critical to find factors that regulate DNA methylation states in reprogramming. Here, we found that the miR-29 family is an important epigenetic regulator during human somatic cell reprogramming. Our global DNA methylation and hydroxymethylation analysis shows that DNA demethylation is a major event mediated by miR-29a depletion during early reprogramming, and that iPSCs derived from miR-29a depletion are epigenetically closer to ESCs. Our findings uncover an important miRNA-based approach to generate clinically robust iPSCs. PMID- 27373927 TI - Potential Pitfalls of the Mx1-Cre System: Implications for Experimental Modeling of Normal and Malignant Hematopoiesis. AB - Conditional knockout mice are commonly used to study the function of specific genes in hematopoiesis. Different promoters that drive Cre expression have been utilized, with the interferon-inducible Mx1-Cre still being the most commonly used "deleter strain" in experimental hematology. However, different pitfalls associated with this system could lead to misinterpretation in functional studies. We present here two of these issues related to the use of Mx1-Cre: first, a high spontaneous recombination rate when applying commonly used techniques in experimental hematology, and second, undesired short-term consequences of the use of polyinosinic:polycytidylic acid, including changes in cellular phenotypes that, however, resolve within days. Our studies emphasize therefore that proper controls are crucial when modeling gene deletion using the Mx1-Cre transgene. PMID- 27373928 TI - Propofol infusion syndrome: early blood purification to the rescue? PMID- 27373930 TI - Remifentanil for labour analgesia. PMID- 27373929 TI - Metformin inhibits Branched Chain Amino Acid (BCAA) derived ketoacidosis and promotes metabolic homeostasis in MSUD. AB - Maple Syrup Urine Disease (MSUD) is an inherited disorder caused by the dysfunction in the branched chain keto-acid dehydrogenase (BCKDH) enzyme. This leads to buildup of branched-chain keto-acids (BCKA) and branched-chain amino acids (BCAA) in body fluids (e.g. keto-isocaproic acid from the BCAA leucine), leading to numerous clinical features including a less understood skeletal muscle dysfunction in patients. KIC is an inhibitor of mitochondrial function at disease relevant concentrations. A murine model of intermediate MSUD (iMSUD) shows significant skeletal muscle dysfunction as by judged decreased muscle fiber diameter. MSUD is an orphan disease with a need for novel drug interventions. Here using a 96-well plate (liquid chromatography- mass spectrometry (LC-MS) based drug-screening platform we show that Metformin, a widely used anti-diabetic drug, reduces levels of KIC in patient-derived fibroblasts by 20-50%. This Metformin-mediated effect was conserved in vivo; Metformin-treatment significantly reduced levels of KIC in the muscle (by 69%) and serum (by 56%) isolated from iMSUD mice, and restored levels of mitochondrial metabolites (e.g. AMP and other TCA). The drug also decreased the expression of mitochondrial branched chain amino transferase (BCAT) which produces KIC in skeletal muscle. This suggests that Metformin can restore skeletal muscle homeostasis in MSUD by decreasing mitochondrial KIC production. PMID- 27373931 TI - Reducing Flightless I expression decreases severity of psoriasis in an imiquimod induced murine model of psoriasiform dermatitis. AB - BACKGROUND: Psoriasis is a common chronic skin condition characterized by excessive inflammation and aberrant epidermal proliferation. Flightless I (Flii) is an actin-remodelling protein that regulates these processes, suggesting a possible role in psoriasis. OBJECTIVES: We sought to determine whether a benefit in psoriasiform dermatitis might occur after modulating Flii gene expression or reducing its levels using neutralizing antibodies. METHODS: Biopsies of psoriatic skin lesions from patients were assessed for Flii levels. Psoriasis-like lesions were induced in Flii heterozygous (Flii+/- ), wild-type (Flii+/+ ) and Flii transgenic (FliiTg/Tg ) mice using topical application of imiquimod. Additionally, psoriasis-induced wild-type mice were treated with topical application of Flii neutralizing antibodies and erythema, inflammation and histology were assessed. RESULTS: Flii was elevated in psoriatic lesions from patients with psoriasis compared with normal human skin. Reducing Flii decreased erythema, inflammatory cell infiltrate, proinflammatory cytokines and the thickness of the epidermis. Topical application of Flii neutralizing antibodies to wild-type mice treated with imiquimod resulted in significantly reduced psoriasiform dermatitis. CONCLUSIONS: Flii is a novel target involved in psoriasiform dermatitis and reducing cutaneous Flii could potentially be a new approach for treating patients with psoriasis. PMID- 27373932 TI - Cervical Spine Surgery: Approach-Related Complications. AB - OBJECTIVE: Cervical spine surgery is a common procedure for treatment of wide variety of pathologies. In this paper we report approach-related complication rates experienced by our patients. METHODS: We retrospectively evaluated data from patients who were treated surgically for cervical pathologies from February 2011 to October 2013. Medical records were collected and evaluated. We compared the anterior cervical approach with the posterior cervical approach for patients operated for all cervical pathologies, and a subanalysis was performed for patients with cervical myelopathy. RESULTS: The study included 251 patients (192 anterior vs. 59 posterior). The anterior approach patients were younger (not significant), but the indications for surgery varied significantly. Mean number of levels treated was 2.2 and 3.5 for anterior and posterior approaches, respectively (statistically significant). Neurologic status change was favorable for both surgical approaches. Total and deep wound infection rates (5.8% vs. 11.9%; P = 0.008; 0.5% vs. 8.5%; P < 0.0005) were significantly greater for the posterior approach As well as total complication rate (7.8% vs. 20.3%; P = 0.005). A subanalysis that included only cervical myelopathy patients (131 anterior vs. 33 posterior) demonstrated again greater levels of deep wound infections and total infection rates for posterior approach (0% vs. 12%; P < 0.0005; 12% vs. 1.5%; P < 0.005). Total complication rate in the myelopathy group was greater for the posterior approach (6.1% vs. 18.1%; P = 0.026). CONCLUSIONS: Both the posterior and the anterior approaches are highly efficacious in preventing neurologic deterioration and in most cases improve neurological function. This study demonstrates that the anterior approach was associated with significantly lower rates of complication especially infection related complications. PMID- 27373933 TI - CREST Study Update. PMID- 27373934 TI - Intracranial Infantile Myofibromatosis Mimicking Malignant Brain Tumor: A Case Report and Literature Review. AB - BACKGROUND: Myofibroma is a fibrous tumor of infancy that sometimes affects a single patient in a multiple fashion (infantile myofibromatosis). Its intracranial involvement is extremely rare, and its clinical picture has been poorly characterized. Here we report an interesting case of myofibromatosis with an intracranial lesion that behaved like an aggressive tumor and yet demonstrated very benign pathology. CASE DESCRIPTION: A 36-year-old man had never been diagnosed with infantile myofibromatosis despite his lifelong history of multiple tumors of various diagnoses. He presented with simple partial seizure and progressive right finger paresis. A series of brain magnetic resonance imaging scans revealed a rapidly growing lesion at his left frontal convexity, which corresponded to a high uptake area on a (18)F-fluorodeoxyglucose-positron emission tomography scan, highly suspicious of malignancy. He underwent complete tumor resection and his symptoms quickly resolved postoperatively. The pathological diagnosis was myofibroma with a MIB-1 labeling index of 1%-2%. A retrospective review of his previous tumors demonstrated the same pathology, which led to the diagnosis of myofibromatosis. Follow-up magnetic resonance imaging illustrated stabilization or regression of other preexisting lesions as well as formation of a new intracranial lesion. CONCLUSIONS: The discrepancy between rapid tumor growth associated with increased uptake on metabolic imaging and benign pathologic findings with a low proliferative index is noteworthy and should be recognized in the management of an intracranial lesion in a patient with infantile myofibromatosis. Given de novo formation of a lesion in this adult patient, long-term follow-up is essential in this disease. PMID- 27373935 TI - Neurocritical Care in China: Past, Present, and Future. AB - Despite the lack of resources and materials, there has been an increasing demand for acute neurologic care owing to the heavy burden of neurocritical illness in most developing countries, including China, where the morbidity and mortality of severe neurologic and neurosurgical disorders remains high. Neurointensive care units did not start appearing in China until the late 1980s. Although great progress has been made over the past 2 decades in the establishment of equipped neurocritical care centers, advancements in medical infrastructure, streamlining of resident training programs, and implementation of multidisciplinary care teams, there remain areas that warrant improvement to care for our growing patient population. Here we review and discuss the history, present state, and future of neurocritical care in the People's Republic of China. PMID- 27373936 TI - Role of Surgical Resection in Patients with Single Large Brain Metastases: Feasibility, Morbidity, and Local Control Evaluation. AB - OBJECTIVE: The aim of this study was to evaluate the safety and the feasibility of surgery for single large brain metastases. METHODS: This retrospective study included 69 patients. All received a "supramarginal resection" according to functional boundaries, defined as a microsurgical excision with an extension larger at least 5 mm greater than the enhancing T1-weighted magnetic resonance imaging (MRI) sequence borders with dural attachment radicalization. Hypofractionated stereotactic radiosurgery on the tumor bed, using 30 Gy in 3 fractions, was performed within 1 month after surgery. Clinical outcome was evaluated at 30 days postoperative and by MRI performed every 3 months. The appearance of postoperative neurologic deficits, local control (LC), brain distant progression (BDP), and overall survival were evaluated. RESULTS: Clinical remission of symptomatology was obtained in 90.5% of patients. None of them had new neurologic deficits or worsening of preoperative functional status. No major complications or cerebrospinal fluid leakage occurred. No residual tumor was detected on postoperative MRI. The median follow-up was 24 months (range 4-33 months). The 1- to 2-year LC was 100%. Twenty-four (29% of) patients had new BDP, and 75% had extracranial progression. The median 1- to 2-year overall survival was 24 months, 91.3% and 73%. At the last observation time, 15 patients (21.7%) were dead and 54 patients (78.3%) were alive. CONCLUSION: Supramarginal resection along with dural attachment radicalization have proved to be safe and effective for selected patients with single large brain metastases. PMID- 27373937 TI - Stabilization of the Craniovertebral Junction with Clivus Plate Constructs: Biomechanical Comparison with Conventional Technique. AB - BACKGROUND: Ventral defect caused by resection of the lesions involving the upper cervical spine commonly has been reconstructed with a fabricated mesh cage. Recently, a clival screw and plate fitted to the osseous anatomy of the craniovertebral junction was developed for this pathologic status. OBJECTIVE: To evaluate the stability a clivus plate system fixation (CPSF) for the craniovertebral junction and compare it with a conventional fashioned mesh cage fixation (FMCF). METHODS: Seven human fresh cadaveric specimens (occiput [Oc], atlas [C1], axis [C2], third cervical vertebra [C3], fourth cervical vertebra [C4]) were tested with intact and destabilization-reconstruction conditions. FMCF and CPSF were applied randomly to the clivus to the C3 segment combined with posterior occipitocervical fixation applied from the occiput to C4 segment, respectively. Specimens were subjected to a pure moment of 1.5 Nm in flexion, extension, lateral bending, and axial rotation, respectively. The range of motion (ROM) and neutral zone (NZ) from the occiput to C3 were calculated and compared between two anterior fixations. RESULTS: Motions were reduced significantly in all directions following FMCF and CPSF fixations when compared with the intact. The CPSF resulted in smaller ROM in lateral bending (0.3 degrees vs. 0.6 degrees , P = 0.015), axial rotation (0.6 degrees vs. 1.2 degrees , P = 0.023) and flexion (0.1 degrees vs. 0.3 degrees , P = 0.019), but similar ROM in extension (0.2 degrees vs. 0.4 degrees , P = 0.273) when compared with the FMCF. NZs with the CPSF were 0.1 degrees in flexion-extension, 0.1 degrees in lateral bending and 0.2 degrees in axial rotation, respectively, and similar to NZs with the FMCF. CONCLUSIONS: The clivus plate system fixation is biomechanically superior to the conventional fashioned mesh cage fixation in flexion, lateral bending and axial rotation, but equavalent in extension. PMID- 27373938 TI - Olfactory Groove Meningiomas: Comparison of Extent of Frontal Lobe Changes After Lateral and Bifrontal Approaches. AB - OBJECTIVE: Olfactory groove meningiomas often are behaviorally silent. Numerous surgical approaches have been described in the literature for the successful removal of these meningiomas. Lateral (pterional/frontolateral) and anterior (bifrontal/fronto-orbito-basal) approaches with their various modifications remain the 2 major corridors in resecting them. In this study, we discuss our experience in microsurgical treatment of these tumors at our institution and assess the extent of frontal lobe damage after the resection of tumor. METHODS: We reviewed the medical records of patients who underwent surgical excision of olfactory groove meningiomas from 1990 to 2014. To measure the extent of frontal lobe damage via lateral and anterior approaches, we measured the volume of porencephalic cave in the postoperative magnetic resonance imaging by using Brainlab software. The ratio of volume of porencephalic cave to tumor was measured between 2 sides and 2 approaches. RESULTS: Fifty-seven patients with olfactory groove meningiomas, who underwent 62 microsurgical resection procedures in 1990-2014 were included in the study (74% were more than 5 cm at presentation). Pterional and bifrontal craniotomies were the most commonly used approaches. At follow-up, the volume of porencephalic cave after lateral approach was significantly less in the side contralateral to craniotomy irrespective of tumor size. The difference between ratio of volume of porencephalic cave and initial tumor was significantly less after lateral approaches, when compared to anterior approaches. CONCLUSIONS: Lateral approaches (pterional/frontolateral) resulted in less frontal lobe change and better olfactory preservation in comparison to anterior approaches in present series. PMID- 27373939 TI - A Case of Optic Neuritis Concomitant with Pituitary Tumor During Pregnancy. AB - BACKGROUND: Optic neuritis (ON) is unilateral painful optic nerve inflammation in a young healthy female diagnosed by excluding glaucoma. ON onset during pregnancy is rare, with only 2 cases reported to date. CASE DESCRIPTION: A 35-year-old previously healthy parous woman who was pregnant with her second child suffered rapidly progressive visual acuity loss. Magnetic resonance imaging (MRI) revealed a pituitary tumor. Emergency surgery was performed for optic nerve compression; however, her visual impairment worsened. Postoperative diffusion-weighted MRI showed high intensity in the bilateral optic nerves, and ON was diagnosed. Administration of methylprednisolone was effective, and her visual acuity recovered over 6 months. CONCLUSIONS: Associated pituitary macroadenoma complicated the true diagnosis of ON, because contrast medium cannot be used in pregnant women. The diffusion-weighted MRI findings were useful for diagnosing this complex clinical condition. PMID- 27373940 TI - Heterologous expression and purification of plantaricin NC8, a two-peptide bacteriocin against Salmonella spp. from Lactobacillus plantarum ZJ316. AB - Bacteriocin, which is produced by lactic acid bacteria (LAB), has the potential to act as natural preservatives in the food industry. To develop strategies to overproduce such peptides, plantaricin NC8, a class IIb LAB bacteriocin that consists of two peptides, PLNC8alpha and PLNC8beta, was successfully heterologously expressed in Escherichia coli BL21 (DE3). PLNC8alpha and PLNC8beta peptides were expressed as His6-tag fusion proteins and were separated by Ni(2+) chelating affinity chromatography. To get the PLNC8alpha and PLNC8beta peptides without extra amino acids in the N-terminus, the fusion proteins were cleaved by enterokinase and further purified using the Ni-NTA SefinoseTM Resin Kit. The molecular masses of peptides were checked using Tricine-SDS-PAGE and MALDI-TOF MS. The yield of purified PLNC8alpha was around 2-2.5 mg/L, and the yield of PLNC8beta was around 1.5-2 mg/L. The antimicrobial spectrum of cleaved peptides was detected and the synergistic action of PLNC8alpha and PLNC8beta was preliminarily confirmed. It was found that E. coli was a suitable host for heterologous expression of plantaricin NC8 with a significant yield. Importantly, the bacteriocin appeared to be very active for controlling and inhibiting the food-borne pathogenic Gram-negative bacteria Salmonella spp., and might be useful as a natural preservative candidate. PMID- 27373941 TI - Rhizodegradation potential and tolerance of Avicennia marina (Forsk.) Vierh in phenanthrene and pyrene contaminated sediments. AB - A pot experiment was conducted to investigate the dissipation of phenanthrene and pyrene in spiked sediments with presence of Avicennia marina (Forsk.) Vierh. The rhizosphere environment was set up using a self-design nylon rhizo-bag which divided the sediment into the rhizosphere and non-rhizosphere. Results showed that the dissipation of phenanthrene and pyrene were significantly enhanced in the rhizosphere compared with non-rhizosphere sediments. Plant roots promoted dissipation significantly greater than the contribution of direct plant uptake and accumulation of phenanthrene and pyrene. The activities of antioxidant and detoxification enzymes in roots and leaves significantly increased against oxidative stress with increasing PAH concentrations. Furthermore, a significant relationship (R(2)>0.91) between dissolved organic carbon (DOC) concentrations and the residual of PAHs in rhizosphere and non-rhizosphere sediments was observed after 120days planting. Results indicated that rhizome mediation with A. marina is a useful approach to promote the depletion of PAHs in contaminated mangrove sediments. PMID- 27373942 TI - Impact of prolonged storm activity on the Ecological Status of intertidal benthic habitats within oyster (Crassostrea gigas) trestle cultivation sites. AB - The Ecological Status (ES; sensu the Water Framework Directive) of intertidal benthic communities within six oyster trestle cultivation sites was found to be negatively impacted along the access routes to trestles in a 2013 study. All cultivation sites occur within Natura 2000 sites. The current study revisited four of the 2013 cultivation sites in February 2014 one month after the storm activity of winter 2013/14 to test if the compaction effect along access routes persisted after the storms. Three levels of the fixed factor treatment were sampled; immediately below the trestles, along the access route and 300m away from any anthropogenic activity. The compaction effect at the Access treatment persisted in spite of the major storm activity. The current study showed the IQI to be effective for assessing the impacts of aquaculture and highlights the IQI as a tool for monitoring Conservation Status of intertidal communities under the Habitats Directive. PMID- 27373943 TI - Twenty two years of sewage sludge marine disposal monitoring in the Eastern Mediterranean Sea: Impact on sediment quality and infauna and the response to load reduction. AB - Effects of sewage sludge disposal on sediments and infauna are presented in a unique long-term (22years) data set from the Eastern Mediterranean. While organic carbon (Corg) and metals affected sediment quality in an area which size varied seasonally, the infauna exhibited seasonal "boom and bust" cycle. Metal concentrations declined following load reduction. However, Corg did not decrease and infaunal abundance, closely related to Corg, varied with changes in environmental forcing. Mild winters affected the infaunal populations at the heavily impacted stations, due to anoxic conditions. Planned cessation of disposal is estimated to reduce Corg and metal concentrations to pre-discharge levels. Yet the resettling biota is expected to differ significantly from the pre discharge one and consist in large part of Erythraean non indigenous species. PMID- 27373944 TI - Turning the tide on mangrove loss. PMID- 27373945 TI - Oil spill impacts on mangroves: Recommendations for operational planning and action based on a global review. AB - Mangrove tidal wetland habitats are recognised as highly vulnerable to large and chronic oil spills. This review of current literature and public databases covers the last 6 decades, summarising global data on oil spill incidents affecting, or likely to have affected, mangrove habitat. Over this period, there have been at least 238 notable oil spills along mangrove shorelines worldwide. In total, at least 5.5milliontonnes of oil has been released into mangrove-lined, coastal waters, oiling possibly up to around 1.94millionha of mangrove habitat, and killing at least 126,000ha of mangrove vegetation since 1958. However, there were assessment limitations with incomplete and unavailable data, as well as unequal coverage across world regions. To redress the gaps described here in reporting on oil spill impacts on mangroves and their recovery worldwide, a number of recommendations and suggestions are made for refreshing and updating standard operational procedures for responders, managers and researchers alike. PMID- 27373946 TI - Behavioral verification of associative learning in whiskers-related fear conditioning in mice. AB - Fear-conditioning is one of the most widely used paradigms in attempts to unravel the processes and mechanisms underlying learning and plasticity. In most of the Pavlovian conditioning paradigms auditory stimulus is used as a conditioned stimulus (CS), but conditioning can be accomplished also to tactile CS. The whisker-to-barrel tactile system in mice offers convenient way to investigate the brain pathways and mechanisms of learning, and plasticity of the brain cortex. To support a claim that an animal learns during conditioning session and that the plastic changes are associative in nature, objective measures of behavior are necessary. Multiple types of conditioned responses can develop, depending on the training situation, CS and unconditioned stimulus (UCS) characteristics. These include physiological responses, such as salivation, heart rate, galvanic skin reaction, and also behavioral responses, such as startle reflex potentiation or suppression of the ongoing behavior. When studying learning with the whisker system in behaving mice, stimulation of individual whiskers in a well-controlled manner may require animal restrain with a disadvantage of only limited behavioral responses observed. Stimulation of whiskers in the neck-restraining apparatus evokes head movements. When whiskers stimulation (CS) is paired with an aversive UCS during conditioning, the head movements decrease in the course of the training. This reaction, called minifreezing, resembles freezing response, frequently used behavioral measure, however applicable only in freely moving animals. This article will review experimental evidences confirming that minifreezing is a relevant index of association formation between the neutral CS and the and the aversive UCS. PMID- 27373947 TI - Functional correlates of brain aging: beta and gamma frequency band responses to age-related cortical changes. AB - The brain as a system with gradually declined resources by age maximizes its performance by neural network reorganization for greater efficiency of neuronal oscillations in a given frequency band. Whether event-related high-frequency band responses are related to plasticity in neural recruitment contributed to the stability of sensory/cognitive mechanisms accompanying aging or are underlined pathological changes seen in aging brain remains unknown. Aged effect on brain electrical activity was studied in auditory discrimination task (low-frequency and high-frequency tone) at particular cortical locations in beta (beta1: 12.5 20; beta2: 20.5-30 Hz) and gamma frequency bands (gamma1: 30.5-49; gamma2: 52-69 Hz) during sensory (post-stimulus interval 0-250 ms) and cognitive processing (250-600 ms). Beta1 activity less affected by age during sensory processing. Reduced beta1 activity was more widespread during cognitive processing. This difference increased in fronto-parietal direction more expressed after high frequency tone stimulation. Beta2 and gamma activity were more pronounced with progressive age during sensory processing. Reducing regional-process specificity with progressing age characterized age-related and tone-dependent beta2 changes during sensory, but not during cognitive processing. Beta2 and gamma activity diminished with age on cognitive processes, except the higher frontal tone dependent gamma activity during cognitive processing. With increasing age, larger gamma2 activity was more expressed over the frontal brain areas to high tone discrimination and hand reaction choice. These gamma2 differences were shifted from posterior to anterior brain regions with advancing age. The aged influence was higher on cognitive processes than on perceptual ones. PMID- 27373948 TI - Inhibition of neuronal and inducible nitric oxide synthase does not affect the analgesic effects of NMDA antagonists in visceral inflammatory pain. AB - Previously we described the antinociceptive effect of magnesium sulfate and dizocilpine (MK-801) in the visceral and somatic rat models of pain. In the somatic model of pain, we established the influence of selective inhibitors of neuronal and inducible nitric oxide synthase on the antihyperalgesic effects of magnesium sulfate and dizocilpine. Therefore, the objective of the present study was to determine in the rat model of visceral pain whether same mechanisms are involved in the antinociceptive action of magnesium sulfate and dizocilpine. Analgesic activity was assessed using the acetic acid-induced writhing test in rats. Subcutaneous injection of either magnesium sulfate (15 mg/kg) or dizocilpine (0.01 mg/kg) decreased the number of writhes by about 60 and 70%, respectively. The role of nitric oxide on the effects of magnesium sulfate and dizocilpine was evaluated using selective inhibitor of neuronal (N-omega-Propyl-L arginine hydrochloride (L-NPA)) and inducible (S-methylisothiourea (SMT)) nitric oxide synthase, which per se did not affect the number of writhes. We observed that the antinociceptive effect of magnesium sulfate or dizocilpine did not change in the presence of L-NPA (2 and 10 mg/kg, i.p.) and SMT (0.015 and 10 mg/kg, i.p.). We conclude that, nitric oxide produced by neuronal and inducible nitric oxide synthase does not modulate the effects of magnesium sulfate and dizocilpine in the visceral inflammatory model of pain in the rat. PMID- 27373949 TI - Pharmacokinetics and pharmacodynamics of a novel Acetylcholinesterase Inhibitor, DMNG-3. AB - DMNG-3(3beta-Methyl-[2-(4-nitrophenoxy)ethyl]-amino]con-5-enine), is a new and the potentially most potent acetylcholinesterase inhibitor recently obtained from conessine by N-demethylation and nucleophilic substitution reaction. In the present study, a step-down passive avoidance test was used to investigate whether DMNG-3 could modulate impairment of learning and memory induced by scopolamine, and a high performance liquid chromatography(HPLC) method for the determination of DMNG-3 in biological samples was applied to study its pharmacokinetics and tissues distribution. Separation was achieved on C18 column using a mobile phase consisting methanol-water (70:30, v/v) at a flow rate of 1.0ml/min. The intra- and inter-day precisions were good and the RSD was all lower than 1.30%. The mean absolute recovery of DMNG-3 in plasma ranged from 88.55 to 96.45 %. Our results showed oral administration of DMNG-3(10,25,50 mg/kg/day) can significantly improve the latency and number of errors and had a positive effect of improvement of learning and memory in mice in passive avoidance tests. The elimination half life (T1/2) was 14.07+/-1.29, 15.87+/-1.03h, and the total clearance (CL) values were 0.70+/-0.11, 0.78+/-0.13 L/h/kg, respectively. The pharmacokinetic studies showed that DMNG-3 has a slowly clearance and large distribution volume in experimental animals, and its disposition is linear over the range of doses tested. The liver, small intestine, stomach, and large intestine were the major distribution tissues of DMNG-3 in mice. It was found that DMNG-3 could be detected in brain, suggesting that DMNG-3 can cross the blood-brain barrier. The present study shows that DMNG-3 can be possible developed as a new drug for the treatment of Alzheimer's disease in the future. PMID- 27373950 TI - Surgical injury-induced early neocortical microvascular changes and characteristics of the cells populating the peri-lesion zone. AB - Adult mammalian brain contains a number of specialized neurovascular structures termed "niches" that act as sources of neuronal cells throughout the individual's life. Some of the niches generate neurons to satisfy the need for 'replacement' neurons within the same or closely located brain structures, whereas the other can provide such cells for more distant destinations in the brain. A common characteristic of known neurovascular niches is the presence of a complex 3 dimensional network of basal lamina processes, called fractones. It apparently plays a major role in communication between the various niche-populating cell types as well as in niche activity and output. We hypothesized that similar niches may form ad hoc after a mechanical brain trauma, and tested this possibility in a rat model of surgical brain injury. Four days after removing a small fragment of sensorimotor cortex, the peri-wound region showed numerous symptoms of active repair and remodeling of brain parenchyma, including the presence of multiple cell types of immature phenotypes. The latter, as shown by a variety of light and electron microscopy techniques, included endothelial cell precursors as well as nestin-positive immature neural cells of astrocytic or non glial characteristics. However, there was no evidence of in situ neurogenesis or a considerable migration of cells from SVZ. The centers of the said repair processes were capillary blood vessels connected with basal lamina-formed fractones. These results indicate that surgical brain trauma causes the formation of a vascular niche with no apparent neurogenic potential. PMID- 27373951 TI - Effects of harmonics on aesthetic judgments of music: an ERP study involving laypersons and experts. AB - The purpose of the study was to test whether aesthetic judgments of music are affected by expertise or harmonic violation of musical sequences. The participants were 14 musical experts and 13 laypersons; they were asked to judge the beauty and correctness of extracts from J. S. Bach's chorales. Experts and laypersons showed different late positive potential (LPP) responses to the appraisal of correctness. LPP also proved to be sensitive to the extent to which the extracts violated harmonic expectations. The relationship between the early right anterior negativity potential (ERAN) and the harmonic correctness of chords was similar in laypersons and experts. PMID- 27373952 TI - Prolonged activity evokes potentiation and the "sag" phenomenon in slow motor units of rat soleus. AB - Slow motor units (MUs) have no sag in their unfused tetani. This study in anesthetized rats shows that the sag can be observed in slow soleus MUs after prolonged activity. Twitches and unfused tetanic contractions were recorded from male (n=35) and female (n=39) MUs before and after the four minutes of the fatigue test (trains of 13 pulses at 40 Hz repeated every second). After this activity twitch contractions potentiated and a shift in the steep part of the force-frequency curve towards lower frequencies was observed in both sexes. Initially no sag was visible in unfused tetani, but after the fatigue test the phenomenon was observed in 77% of male, while in 13% of female MUs, the result consistent with the previously reported higher content of IIa myosin and faster contraction of MUs in male soleus. The decomposition of tetani with sag into trains of twitch-shape responses to consecutive stimuli revealed higher forces of initial decomposed twitches than later. The revealed alterations the force development due to long-lasting activation of slow MUs were sex-related and more pronounced in male soleus. PMID- 27373953 TI - Somatic and dendritic perforated-patch recordings reveal b-adrenergic receptor induced depolarization in medial prefrontal cortex pyramidal neurons. AB - The aim of this perforated-patch study was to test the effect of isoproterenol on the membrane potential in mPFC (medial prefrontal cortex) pyramidal neurons. Isoproterenol depolarized the membrane potential recorded from the soma. This effect was absent in the presence of metoprolol, suggesting the involvement of beta1-adrenergic receptors. The adenylate cyclase activator forskolin also depolarized the membrane potential. Moreover, the effect of isoproterenol was abolished by the adenylate cyclase inhibitor SQ 22536. This suggested that adenylate cyclase was involved in mediating the effect of the beta-adrenergic receptor agonist. The isoproterenol-induced depolarization persisted after inhibition of protein kinase A with H-89. The effect of beta-adrenergic receptor activation on the membrane potential was dependent on Ih channels because it was abolished in the presence of the Ih channel inhibitor ZD 7288. Dendritic recordings were also performed. In the dendritic segments between 100 microm and 150 microm from the soma and between 200 microm and 250 microm from the soma, isoproterenol also depolarized the membrane potential. The magnitude of the beta adrenergic receptor-stimulated depolarization was the same in the soma and in both dendritic localizations. The depolarization exerted by isoproterenol may influence PFC cognitive functions. PMID- 27373954 TI - Woodward's Words: Elegant and Commanding. AB - Robert Burns Woodward's publications exhibit a beauty and majesty infrequently seen in the scientific literature. Excerpts from Woodward's publications are presented along with a discussion of his literary personality and the effect of his writings on his contemporaries and on the style of the chemical literature that followed. PMID- 27373955 TI - Biotic interchange between the Indian subcontinent and mainland Asia through time. AB - Biotic interchange after the connection of previously independently evolving floras and faunas is thought to be one of the key factors that shaped global biodiversity as we see it today. However, it was not known how biotic interchange develops over longer time periods of several million years following the secondary contact of different biotas. Here we present a novel method to investigate the temporal dynamics of biotic interchange based on a phylogeographical meta-analysis by calculating the maximal number of observed dispersal events per million years given the temporal uncertainty of the underlying time-calibrated phylogenies. We show that biotic influx from mainland Asia onto the Indian subcontinent after Eocene continental collision was not a uniform process, but was subject to periods of acceleration, stagnancy and decrease. We discuss potential palaeoenvironmental causes for this fluctuation. PMID- 27373956 TI - Colloidal particle adsorption at liquid interfaces: capillary driven dynamics and thermally activated kinetics. AB - The adsorption of single colloidal microparticles (0.5-1 MUm radius) at a water oil interface has been recently studied experimentally using digital holographic microscopy [Kaz et al., Nat. Mater., 2012, 11, 138-142]. An initially fast adsorption dynamics driven by capillary forces is followed by an unexpectedly slow relaxation to equilibrium that is logarithmic in time and can span hours or days. The slow relaxation kinetics has been attributed to the presence of surface "defects" with nanoscale dimensions (1-5 nm) that induce multiple metastable configurations of the contact line perimeter. A kinetic model considering thermally activated transitions between such metastable configurations has been proposed [Colosqui et al., Phys. Rev. Lett., 2013, 111, 028302] to predict both the relaxation rate and the crossover point to the slow logarithmic regime. However, the adsorption dynamics observed experimentally before the crossover point has remained unstudied. In this work, we propose a Langevin model that is able to describe the entire adsorption process of single colloidal particles by considering metastable states produced by surface defects and thermal motion of the particle and liquid interface. Invoking the fluctuation dissipation theorem, we introduce a drag term that considers significant dissipative forces induced by thermal fluctuations of the liquid interface. Langevin dynamics simulations based on the proposed adsorption model yield close agreement with experimental observations for different microparticles, capturing the crossover from (fast) capillary driven dynamics to (slow) thermally activated kinetics. PMID- 27373957 TI - Unilateral flank ovariohysterectomy in guinea pigs (Cavia porcellus). AB - AIMS: To describe a simple, minimally invasive method of ovariohysterectomy via a unilateral flank approach in guinea pigs, for use in routine desexing of healthy female guinea pigs or treatment of ovarian cysts. METHODS: The subjects of this retrospective study were 41 client-owned guinea pigs submitted for routine desexing or treatment of ovarian cysts. They included 16 healthy female guinea pigs aged 8-12 months (Group 1), and 15 females aged from 9 months to 3 years (Group 2), and 10 females aged from 3 to 7 years (Group 3) with different-sized ovarian cysts. Prior to surgery, the animals received clinical examination, blood testing (complete blood count and serum biochemistry profile) and examination of the abdomen using ultrasonography, to assess the condition of the reproductive tract and ensure the guinea pigs were fit for surgery. Ovariohysterectomy was performed via a unilateral flank incision made close to the erector spinae muscle starting approximately 1 cm caudal to the last rib. Both ovaries, uterine horns, and the uterine cervix were localised, ligated, and dissected through this unilateral retroperitoneal incision. RESULTS: Ovariohysterectomy was successfully completed via a single flank incision in 38/41 (93%) guinea pigs. Three guinea pigs with ovarian cysts from Group 3, which were >6 years old died during surgery due to circulatory and respiratory failure under anaesthesia. In the remaining 38 cases, surgery proceeded without complications. A further two guinea pigs from Group 3 were reluctant to move or eat for the first 3 days after surgery but recovered after provision of supportive care. All 38 animals fully recovered and wound healing was normal. CONCLUSIONS: This is the first report of ovariohysterectomy via a unilateral flank incision in guinea pigs. This approach is a simple, minimally invasive and safe alternative to the midline or bilateral flank approaches currently used for surgery of the reproductive tract in guinea pigs. PMID- 27373958 TI - Rex in Clostridium kluyveri is a global redox-sensing transcriptional regulator. AB - Clostridium kluyveri is unique in fermenting ethanol and acetate to butyrate, caproate, and H2. The genes encoding butyrate-producing enzymes, including electron-bifurcating butyryl-CoA dehydrogenase/electron transfer flavoprotein complex and NADH-dependent reduced ferredoxin:NADP(+) oxidoreductase, form a cluster, which is preceded by a gene annotated as the transcriptional regulator Rex. Northern blotting and RT-PCR experiments indicated that the gene cluster forms a large transcriptional unit that possibly includes several small transcriptional units. The deduced Rex protein contains a winged helix DNA binding domain and a Rossmann fold potentially interacting with NAD(H). Bioinformatics analysis revealed that Rex can bind the promoter regions of numerous genes, which are involved in carbon and energy metabolism, including NADH oxidation, hydrogen production, ATP synthesis, butyrate formation, and succinate metabolism. Rex may regulate the transcription of genes encoding certain transcriptional regulators and transporters. Electrophoretic mobility shift and isothermal titration calorimetry assays revealed that Rex specifically formed protein-DNA complexes with the promoter regions of target genes, which could be inhibited by NADH but restored by an excess amount of NAD(+). These results suggest that Rex plays a key role in the carbon and energy metabolism of C. kluyveri as a global transcriptional regulator in response to the cellular NADH/NAD(+) ratio. PMID- 27373959 TI - Religiosity and telomere length: One step forward, one step back. PMID- 27373960 TI - Family functioning mediates adaptation in caregivers of individuals with Rett syndrome. AB - OBJECTIVE: The objective of this study was to investigate factors related to family functioning and adaptation in caregivers of individuals with Rett syndrome (RS). METHODS: A cross-sectional quantitative survey explored the relationships between demographics, parental self-efficacy, coping methods, family functioning and adaptation. A forward-backward, step-wise model selection procedure was used to evaluate variables associated with both family functioning and adaptation. Analyses also explored family functioning as a mediator of the relationship between other variables and adaptation. RESULTS: Bivariate analyses (N=400) revealed that greater parental self-efficacy, a greater proportion of problem focused coping, and a lesser proportion of emotion-focused coping were associated with more effective family functioning. In addition, these key variables were significantly associated with greater adaptation, as was family functioning, while controlling for confounders. Finally, regression analyses suggest family functioning as a mediator of the relationships between three variables (parental self-efficacy, problem-focused coping, and emotion-focused coping) with adaptation. CONCLUSION: This study demonstrates the potentially predictive roles of expectations and coping methods and the mediator role of family functioning in adaptation among caregivers of individuals with RS, a chronic developmental disorder. PRACTICE IMPLICATIONS: A potential target for intervention is strengthening of caregiver competence in the parenting role to enhance caregiver adaptation. PMID- 27373961 TI - Longitudinal testing of the Information-Motivation-Behavioral Skills model of self-care among adults with type 2 diabetes. AB - OBJECTIVE: The study's aim was to test prospective associations between information, motivation, and behavioral skills (IMB model) and self-care behaviors (diet, exercise, and blood glucose testing) among patients with type 2 diabetes. METHODS: 295 participants were surveyed one (T1), six (T2), and 12 (T3) months after a diabetes course. Cross-lagged panel analyses were performed to test unidirectional and bidirectional relationships between IMB model variables and self-care behaviors. RESULTS: Blood-glucose testing at T1 was positively related to information at T2, which in turn was positively related to blood glucose testing at T3. Controlled motivation at T1 was positively related to exercise at T2. Autonomous motivation at T2 was positively associated with exercise at T3. There was a positive bidirectional relationship across time between behavioral skills and general diet. CONCLUSION: Patterns of prospective associations between IMB model variables and diabetes self-care depend on the self-care behavior considered. This model offers an interesting framework for examining how diabetes self-care behaviors evolve. PRACTICE IMPLICATIONS: Diabetes education programs should provide information about current health status and promote experiential learning to help patients realize the impact of their behaviors on glycemic control; should foster autonomous motivation for long term change; and should build on patients' strengths and skills. PMID- 27373963 TI - The next 20 years of hospital medicine: Continuing to foster the mind, heart, and soul of our field. PMID- 27373962 TI - Health literacy and barriers to health information seeking: A nationwide survey in South Korea. AB - OBJECTIVE: To identify the level of health literacy and barriers to information seeking and to explore the predictors of health literacy. METHODS: A cross sectional descriptive design was used. A total of 1000 Korean adults were recruited through proportional quota sampling. Health literacy, barriers to health information seeking, sociodemographics, and health-related characteristics were surveyed. Descriptive statistics and binary logistic regression were performed for data analysis. RESULTS: About 61% of participants were classified as inadequately health literate. "No health fairs/activities near home" was the most frequently reported barrier. Older age, lower education, living in the capital city, barriers regarding how to get information and access to expensive books and magazines were predictors of inadequate health literacy. CONCLUSION: Strategies for improving health literacy and reducing barriers to health information seeking should be designed. Education on how to access health-related information with easily accessible sources either free or inexpensive could be a way to help adults with limited health literacy. PRACTICE IMPLICATIONS: Health care professionals should assess clients' health literacy levels, particularly amongst those who are older or have less education. They should provide clients with information on how to access credible and readily available sources of health-related information, considering their health literacy level. PMID- 27373964 TI - Diabetes research in China: making progress. PMID- 27373965 TI - Correction to Lancet Diabetes Endocrinol 2016; published online May 27. http://dx.doi.org/10.1016/S2213-8587(16)30041-9. PMID- 27373966 TI - Electrolyte transport pathways induced in the midgut epithelium of Drosophila melanogaster larvae by commensal gut microbiota and pathogens. AB - KEY POINTS: The digestive tract of larval and adult Drosophila is an excellent analogue of the mammalian gut. Enterocytes of the posterior midgut are separated by septa, with no paracellular path, and therefore perform both immune and transport functions. Using microperfusion electrophysiology, we show that larvae emerging from the embryo into sterile medium have symmetrical apical and basal membrane conductances while larvae emerging into non-sterile medium have apical membranes fivefold more conductive than basal membranes. The channels inserted into the apical membranes could originate in microbiata or host and mediate recognition of microbes. Entomopathogenic cyclic peptide toxins deplete intracellular ions reversibly, forming transient ion channels that do not conduct water, unlike an ionophore like nystatin that depletes ions irreversibly. We show the feasibility of studying the interaction of a single microbial species, or tractable combinatorials of microbial species, with only enterocytes in the primary epithelial barrier. ABSTRACT: Microbiota colonizing exposed epithelial surfaces are vital for sustenance of metazoan life, but communication between microbiota, epithelial cells and the host immune system is only beginning to be understood. We address this issue in the posterior midgut epithelium of Drosophila larvae where nutrient transport and immune functions are exclusively transcellular. We showed that larvae emerging into a sterile post-embryonic environment have symmetrical apical and basal membranes. In contrast, larvae emerging into non-sterile media, the source of microbiota, have markedly asymmetrical membranes, with apical membrane conductance more than fivefold higher than the basal membrane. As an example of pathogen action, we showed that the entomopathogenic fungal toxin destruxin A (Dx) depleted intracellular ions. Reversibility of action of Dx was verified by bilayer reconstitution in forming transient non-specific channels that conduct ions but not water. Dx was also less effective from the apical side as compared to the basal side of the epithelium. We also showed that intercellular septa are not conductive in non-sterile cells, even though most cells are isopotential. Luminal microbiota therefore impart asymmetry to the epithelium, by activation of apical membrane conductance, enhancing inter-enterocyte communication, separated by insulating septa, via the gut lumen. These results also open the possibility of studying the basis of bidirectional molecular conversation specifically between enterocytes and microbiota that enables discrimination between commensals and pathogens, establishment of the former, and elimination of the latter. PMID- 27373967 TI - Anti-amyloidogenic effects of glycosphingolipid synthesis inhibitors occur independently of ganglioside alterations. AB - Evidence has suggested that ganglioside abnormalities may be linked to the proteolytic processing of amyloid precursor protein (APP) in Alzheimer's disease (AD) and that pharmacological inhibition of ganglioside synthesis may reduce amyloid beta-peptide (Abeta) production. In this study, we assessed the usefulness of two well-established glycosphingolipid (GSL) synthesis inhibitors, the synthetic ceramide analog D-PDMP (1-phenyl 2-decanoylamino-3-morpholino-1 propanol) and the iminosugar N-butyldeoxynojirimycin (NB-DNJ or miglustat), as anti-amyloidogenic drugs in a human cellular model of AD. We found that both GSL inhibitors were able to markedly inhibit Abeta production, although affecting differently the APP cleavage. Surprisingly, the L-enantiomer of PDMP, which promotes ganglioside accumulation, acted similarly to D-PDMP to inhibit Abeta production. Concurrently, both D- and L-PDMP strongly and equally reduced the levels of long-chain ceramides. Altogether, our data suggested that the anti amyloidogenic effects of PDMP agents are independent of the altered cellular ganglioside composition, but may result, at least in part, from their ability to reduce ceramide levels. Moreover, our current study established for the first time that NB-DNJ, a drug already used as a therapeutic for Gaucher disease (a lysosomal storage disorder), was also able to reduce Abeta production in our cellular model. Therefore, our study provides novel information regarding the possibilities to target amyloidogenic processing of APP through modulation of sphingolipid metabolism and emphasizes the potential of the iminosugar NB-DNJ as a disease modifying therapy for AD. PMID- 27373968 TI - Immune Reconstitution Syndrome secondary to Rhodococcus equi infection in a patient with HIV and Burkitt's lymphoma. AB - Immune Reconstitution Syndrome (IRIS) has been associated with a variety of infections in patients with human immunodeficiency virus (HIV). However, we are reporting the first case of IRIS secondary to Rhodococcus equi (R. equi) in a patient with HIV. We report the case of a 48-year-old male found to have HIV infection in the setting of Burkitt's lymphoma. While on anti-retroviral therapy and chemotherapy, he had developed IRIS secondary to R. equi that manifested as a cavitating pneumonia. This report outlines the successful management of the R. equi infection with the use of a combination of antibiotics, radiographic follow up and suppressive antibiotic while on chemotherapy. PMID- 27373970 TI - Unraveling the immunopathogenesis of glomerular disease. AB - Immune-mediated damage to glomerular structures is largely responsible for the pathology associated with the majority of glomerular diseases. Therefore, a detailed understanding of the basic immune mechanisms responsible for glomerular damage is needed to inform the design of novel intervention strategies. Glomerular injury of immune origin is complex and involves both inflammatory and non-inflammatory processes driven by elements of the innate and adaptive immune system. This review summarizes the basic immune mechanisms that cause glomerular injury leading to the nephritic and nephrotic syndromes. A major focus of the review is to highlight the mechanisms by which antibodies cause glomerular injury through their interactions with glomerular cells, complement proteins, phagocytes bearing complement and Fcgamma receptors, and dendritic cells expressing the neonatal receptor for IgG, FcRn. PMID- 27373969 TI - Highly specific and potently activating Vgamma9Vdelta2-T cell specific nanobodies for diagnostic and therapeutic applications. AB - Vgamma9Vdelta2-T cells constitute the predominant subset of gammadelta-T cells in human peripheral blood and have been shown to play an important role in antimicrobial and antitumor immune responses. Several efforts have been initiated to exploit these cells for cancer immunotherapy, e.g. by using phosphoantigens, adoptive cell transfer, and by a bispecific monoclonal antibody based approach. Here, we report the generation of a novel set of Vgamma9Vdelta2-T cell specific VHH (or nanobody). VHH have several advantages compared to conventional antibodies related to their small size, stability, ease of generating multispecific molecules and low immunogenicity. With high specificity and affinity, the anti-Vgamma9Vdelta2-T cell receptor VHHs are shown to be useful for FACS, MACS and immunocytochemistry. In addition, some VHH were found to specifically activate Vgamma9Vdelta2-T cells. Besides being of possible immunotherapeutic value, these single domain antibodies will be of great value in the further study of this important immune effector cell subset. PMID- 27373971 TI - Evaluation of AD-MSC (adipose-derived mesenchymal stem cells) as a vehicle for IFN-beta delivery in experimental autoimmune encephalomyelitis. AB - Interferon-beta (IFN-beta) is commonly used as a disease modifying drug for the treatment of relapse-remitting multiple sclerosis (RR-MS). However, the underlying mechanism by which IFN-beta mediate this immunosuppressive effect is still unknown. In this study, we analyzed the effects of genetically modified adipose-derived mesenchymal stem cells (AD-MSCs) expressing murine interferon beta (MSCs-VP/IFN-beta) on the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Lymph node mononuclear cells and serum were examined by using RT-PCR and ELISA methods to measure the production of IL-10 and IL-17 gene and protein expression, respectively. Our results indicated that in the MSCs VP/IFN-beta treated group induction of Tregs and IL-10 and reduction of IL-17 were significant. Taken together, we showed that using AD-MSCs expressing IFN beta as an anti-inflammatory agent, offer evidence supporting that the stem cell therapies in EAE conceivably will improve the valuable effects of IFN-beta in this autoimmune disease. PMID- 27373972 TI - Special issue on retinal remodeling. PMID- 27373975 TI - A negative stimulus movement effect in pigeons. AB - Rhesus monkeys and humans perform more accurately in matching-to-sample tasks when the sample stimulus moves through space (Washburn et al., 1989; Washburn, 1993). This Stimulus Movement Effect (SME) is believed to be due to movement increasing attention toward the sample stimulus, creating an easier discrimination between the sample and choice stimuli. To date, there is no evidence for this phenomenon in a non-mammalian species. In the current study, we investigate the possibility of an SME in an avian species. Across three experiments, pigeons were tested with moving and stationary sample stimuli in a non-matching- to-sample task. The area and velocity by which the sample stimulus traveled was manipulated but no advantage for moving over stationary sample trials was found within or across sessions. Even when a delay condition was implemented, there was no advantage for moving sample trials. Contrary to the results found in humans and monkeys, pigeons performed better when the sample was stationary, a negative SME, and no evidence was found that stimulus movement increases discrimination performance. PMID- 27373973 TI - Lens glutathione homeostasis: Discrepancies and gaps in knowledge standing in the way of novel therapeutic approaches. AB - Cataract is the major cause of blindness worldwide. The WHO has estimated around 20 million people have bilateral blindness from cataract, and that number is expected to reach 50 million in 2050. The cataract surgery is currently the main treatment approach, though often associated with complications, such as Posterior Capsule Opacification (PCO)-also known as secondary cataract. The lens is an avascular ocular structure equipped with an unusually high level of glutathione (GSH), which plays a vital role in maintaining lens transparency by regulating lenticular redox state. The lens epithelium and outer cortex are thought to be responsible for providing the majority of lens GSH via GSH de novo synthesis, assisted by a continuous supply of constituent amino acids from the aqueous humor, as well as extracellular GSH recycling from the gamma-glutamyl cycle. However, when de novo synthesis is impaired, in the presence of low GSH levels, as in the aging human lens, compensatory mechanisms exist, suggesting that the lens is able to uptake GSH from the surrounding ocular tissues. However, these uptake mechanisms, and the GSH source and its origin, are largely unknown. The lens nucleus does not have the ability to synthesize its own GSH and fully relies on transport from the outer cortex by yet unknown mechanisms. Understanding how aging reduces GSH levels, particularly in the lens nucleus, how it is associated with age-related nuclear cataract (ARNC), and how the lens compensates for GSH loss via external uptake should be a major research priority. The intent of this review, which is dedicated to the memory of David C. Beebe, is to summarize our current understanding of lens GSH homeostasis and highlight discrepancies and gaps in knowledge that stand in the way of pharmacologically minimizing the impact of declining GSH content in the prevention of age-related cataract. PMID- 27373974 TI - Autophagy and mechanotransduction in outflow pathway cells. AB - Because of elevations in IOP and other forces, cells in the trabecular meshwork (TM) are constantly subjected to mechanical strain. In order to preserve cellular function and regain homeostasis, cells must sense and adapt to these morphological changes. We and others have already shown that mechanical stress can trigger a broad range of responses in TM cells; however, very little is known about the strategies that TM cells use to respond to this stress, so they can adapt and survive. Autophagy, a lysosomal degradation pathway, has emerged as an important cellular homeostatic mechanism promoting cell survival and adaptation to a number of cytotoxic stresses. Our laboratory has reported the activation of autophagy in TM cells in response to static biaxial strain and high pressure. Moreover, our newest data also suggest the activation of chaperon-assisted selective autophagy, a recently identified tension-induced autophagy essential for mechanotransduction, in TM cells under cyclic mechanical stress. In this review manuscript we will discuss autophagy as part of an integrated response triggered in TM cells in response to strain, exerting a dual role in repair and mechanotransduction, and the potential effects of dysregulated in outflow pathway pathophysiology. PMID- 27373976 TI - Effectiveness of a high relaxivity contrast agent administered at half dose in dynamic susceptibility contrast MRI of brain gliomas. AB - PURPOSE: To determine whether half of the approved dose of gadobenate dimeglumine (MultiHance) is as effective as a full dose of gadoterate meglumine (Dotarem) for qualitative and quantitative cerebral blood volume (CBV) perfusion evaluation at 3T in patients with brain gliomas. MATERIALS AND METHODS: We enrolled 65 adult patients in an interindividual comparative study. Patients were randomized to one of two study arms: 33 patients received 0.1 mmol/kg body weight (bw) of gadoterate, 32 patients received 0.05 mmol/kg bw of gadobenate. The patients underwent identical examinations at 3T. Arterial input function (AIF), tissue function (TF), and the maximum tumor CBV (CBV_T) were obtained from each patient. The quality of the CBV maps were independently reviewed by two neuroradiologists blinded to the administered contrast agent. RESULTS: The administration of a half dose of gadobenate led to a roughly 40% reduction in signal drop compared to that achieved with a full dose of gadoterate (P values for AIF and TF maximum and integral were <0.01); quantitative and qualitative assessment of CBV maps revealed no difference between contrast agents (P values for CBV_T of high- and low-grade gliomas, image quality evaluation were 0.87, 0.48, >0.65, respectively) CONCLUSION: The CBV maps obtained with a half dose gadobenate (0.05 mmol/kg bw) are of comparable diagnostic quality as the corresponding images acquired with a full dose of gadoterate (0.1 mmol/kg bw). LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:500-506. PMID- 27373977 TI - Populibacterium corticicola gen. nov., sp. nov., a member of the family Jonesiaceae, isolated from symptomatic bark of Populus * euramericana canker. AB - Four Gram-stain-positive, aerobic, motile bacterial strains were isolated from the bark tissue of Populus * euramericana canker. Growth occurred between 10 and 37 degrees C and at pH 6-10, with optimal growth at 28-30 degrees C and pH 7.0 8.0. Growth occurred at 0-3 % (w/v) salinity. The strains were positive for oxidase and catalase activity. The major fatty acids were anteiso-C15 : 0 and C16 : 0. The phospholipid profiles contained diphosphatidylglycerol, phosphatidylinositol, phosphatidylglycerol, two phospholipids and five glycolipids. The peptidoglycan type was A4alpha, which is based on l-Lys-d-Ser-d Asp. The DNA G+C content was 58.5 mol%. Based on 16S rRNA gene sequence analysis, as well as physiological and biochemical characteristics, the strains are considered to represent a novel species of a new genus in the family Jonesiaceae. The name proposed is Populibacterium corticicola gen. nov., sp. nov. The type strain of Populibacterium corticicola is 2D-4T (=CFCC 11886T=KCTC 33576T). PMID- 27373978 TI - Down-Regulation of SOX2 Underlies the Inhibitory Effects of the Triphenylmethane Gentian Violet on Melanoma Cell Self-Renewal and Survival. AB - Human melanomas contain a population of tumor-initiating cells that are able to maintain the growth of the tumor. We previously showed that the embryonic transcription factor SOX2 is essential for self-renewal and tumorigenicity of human melanoma-initiating cells. However, targeting a transcription factor is still challenging. Gentian violet (GV) is a cationic triphenylmethane dye with potent antifungal and antibacterial activity. Recently, a combination therapy of imiquimod and GV has shown an inhibitory effect against melanoma metastases. Whether and how GV affects melanoma cells remains unknown. Here we show that GV represses melanoma stem cell self-renewal through inhibition of SOX2. Mechanistically, GV hinders EGFR activation and inhibits the signal transducer and activator of transcription-3 [(STAT3)/SOX2] axis. Importantly, we show that GV treatment decreases STAT3 phosphorylation at residue tyrosine 705, thus preventing the translocation of STAT3 into the nucleus and its binding to SOX2 promoter. In addition, GV affects melanoma cell growth by promoting mitochondrial apoptosis and G2 cell cycle arrest. This study shows that in melanoma, GV affects both the stem cell and the tumor bulk compartments, suggesting the potential use of GV in treating human melanoma alone or in combination with targeted therapy and/or immunotherapy. PMID- 27373980 TI - Histamine restores hemorrhage induced hypotension by activating cholinergic neurons in nucleus tractus solitarius. AB - The purpose of the current study is to investigate the functional connections between the central histaminergic and cholinergic systems at NTS level in hypotensive condition. Experiments were carried out in male Wistar Albino rats. The hypotension was achieved by withdrawing a total volume of 1.5ml blood/100g bodyweight over a period of 10min. A microdialysis study was performed in NTS area to measure extracellular ACh and Ch levels. The hemorrhage produced a severe and long-lasting decrease in mean arterial blood pressure (MAP) and increase in extracellular ACh and Ch levels in NTS. Administration of histamine intracerebroventricularly (i.c.v.) or into the NTS reversed the hemorrhagic hypotension by increasing MAP and heart rate. I.c.v. injection of histamine also caused the additional increase in extracellular ACh and Ch levels. Moreover, central histamine injection augmented intracytoplasmic AChE immunoreactivity in NTS. These changes were completely blocked by histaminergic H1 receptor antagonist chlorpheniramine, but histaminergic H2 receptor blocker ranitidine and histaminergic H3/H4 receptor antagonist thioperamide failed to produce these effects. In conclusion, these findings are interpreted that brain histaminergic H1 receptor activation by central histamine injection may promote cholinergic stimulation in the NTS and subsequently reverses the hypotension. PMID- 27373979 TI - Cathepsin L knockdown enhances curcumin-mediated inhibition of growth, migration, and invasion of glioma cells. AB - Curcumin can be used to prevent and treat cancer. However, its exact underlying molecular mechanisms remain poorly understood. Cathepsin L, a lysosomal cysteine protease, is overexpressed in several cancer types. This study aimed to determine the role of cathepsin L in curcumin-mediated inhibition of growth, migration, and invasion of glioma cells. Results revealed that the activity of cathepsin L was enhanced in curcumin-treated glioma cells. Cathepsin L knockdown induced by RNA interference significantly promoted curcumin-induced cytotoxicity, apoptosis, and cell cycle arrest. The knockdown also inhibited the migration and invasion of glioma cells. Our results suggested that the inhibition of cathepsin L can enhance the sensitivity of glioma cells to curcumin. Therefore, cathepsin L may be a new target to enhance the efficacy of curcumin against cancers. PMID- 27373981 TI - The effectiveness of the Danish Organic Action Plan 2020 to increase the level of organic public procurement in Danish public kitchens. AB - OBJECTIVE: To measure the effect of organic food conversion projects on the percentage of organic food used in Danish public kitchens participating in the Danish Organic Action Plan 2020. DESIGN: The current longitudinal study was based on measurements of organic food percentages in Danish public kitchens before and after kitchen employees participated in conversion projects. SETTING: Public kitchens participating in the nine organic food conversion projects under the Danish Organic Action Plan 2020, initiated during autumn 2012 and spring 2013 and completed in summer 2015. SUBJECTS: A total of 622 public kitchens. RESULTS: The average (median) increase in organic food percentage from baseline to follow-up was 24 percentage points (P<0.001) during an overall median follow-up period of 1.5 years. When analysing data according to public kitchen type, the increase remained significant for seven out of eight kitchens. Furthermore, the proportion of public kitchens eligible for the Organic Cuisine Label in either silver (60-90 % organic food procurement) or gold (90-100 % organic food procurement) level doubled from 31 % to 62 %, respectively, during the conversion period. Conversion project curriculum mostly included elements of 'theory', 'menu planning', 'network' and 'Organic Cuisine Label method' to ensure successful implementation. CONCLUSIONS: The study reports significant increases in the level of organic food procurement among public kitchens participating in the Danish Organic Action Plan 2020. Recommendations for future organic conversion projects include adding key curriculum components to the project's educational content and measuring changes in organic food percentage to increase the chances of successful implementation. PMID- 27373982 TI - Topological water wave states in a one-dimensional structure. AB - Topological concepts have been introduced into electronic, photonic, and phononic systems, but have not been studied in surface-water-wave systems. Here we study a one-dimensional periodic resonant surface-water-wave system and demonstrate its topological transition. By selecting three different water depths, we can construct different types of water waves - shallow, intermediate and deep water waves. The periodic surface-water-wave system consists of an array of cylindrical water tanks connected with narrow water channels. As the width of connecting channel varies, the band diagram undergoes a topological transition which can be further characterized by Zak phase. This topological transition holds true for shallow, intermediate and deep water waves. However, the interface state at the boundary separating two topologically distinct arrays of water tanks can exhibit different bands for shallow, intermediate and deep water waves. Our work studies for the first time topological properties of water wave systems, and paves the way to potential management of water waves. PMID- 27373983 TI - Scavenger Receptor Class B Type 1 Deletion Led to Coronary Atherosclerosis and Ischemic Heart Disease in Low-density Lipoprotein Receptor Knockout Mice on Modified Western-type Diet. AB - AIM: Atherosclerosis-prone apolipoprotein E (apoE) or low-density lipoprotein receptor (LDL-R) knockout (KO) mice are generally resistant to developing coronary atherosclerosis (CA) and ischemic heart disease (IHD). However, studies have demonstrated the occurrence of spontaneous CA and IHD in scavenger receptor class B type 1 (SR-BI)/apoE double KO (dKO) mice, which suggests that SR-BI could be a potential target for the prevention and therapy of CA and IHD. This possibility was later investigated in SR-BI/LDL-R dKO mice, but no signs of CA or IHD was identified when mice were fed a normal western-type diet. Here we explored whether SR-BI deletion could result in CA and IHD in LDL-R KO mice when fed a modified western-type diet containing higher (0.5%) cholesterol. METHODS: Cardiac functions were detected by electrocardiography, single photon emission computed tomography (SPECT), echocardiography (Echo) and 2,3,5 triphenyltetrazolium chloride staining. CA was visualized by hematoxylin-eosin staining. RESULTS: After 12 weeks on the modified diet, SR-BI/LDL-R dKO mice developed cardiac ischemia/infarction, together with systolic dysfunction and left ventricular dilatation. CA was most severe at the aortic sinus level to an extent that no dKO mice survived to 20 weeks on the modified diet. None of control mice, however, developed CA or IHD. CONCLUSIONS: SR-BI deletion led to CA and IHD in LDL-R KO mice when fed the modified western-type diet. We established SR-BI/LDL-R dKO mice as a diet-induced murine model of human IHD and developed detection methods, using a combination of SPECT and Echo, for effective in vivo evaluation of cardiac functions. PMID- 27373984 TI - Reference Values for The Triglyceride to High-Density Lipoprotein Cholesterol Ratio and Non-High-Density Lipoprotein Cholesterol in Korean Children and Adolescents: The Korean National Health and Nutrition Examination Surveys 2007 2013. AB - AIM: Cholesterol levels vary throughout childhood and adolescence. The aim of the present study was to evaluate and identify age- and gender-specific reference values for serum lipid concentrations including non-high-density lipoprotein cholesterol (non-HDL-C) and the triglyceride to HDL-C ratio (TG/HDL-C ratio) in apparently healthy Korean children and adolescents. METHODS: A total of 6197 participants aged 10 to 19 years old from the 2007-2013 Korean National Health and Nutrition Examination Survey were analyzed. Serum lipid concentrations were evaluated according to age and gender. RESULTS: The overall mean concentration of non-HDL-C was 105.5+/-25.6 mg/dL, with a significant gender difference: 103.3+/ 26.1 mg/dL in boys and 107.9+/-24.7 mg/dL in girls (p=0.028). The median values of non-HDL-C concentrations in boys and girls, respectively, were 111 and 112 mg/dL in the 10-year-old age group, 95 and 103 mg/dL in the 15-year-old age group, and 109 and 103 mg/dL in the 19-year-old age group. The overall mean TG/HDL-C ratio was 1.74+/-1.22, and there were no significant gender differences: 1.77+/-1.25 in boys and 1.72+/-1.22 in girls (p=0.183). The median values of the TG/HDL-C ratio in boys and girls were 1.16 and 1.00 in the 10-year-olds, 1.54 and 0.95 in the 15-year-olds, and 1.74 and 0.84 in the 19-year-olds, respectively. CONCLUSIONS: Age- and gender-specific reference values for non-HDL-C and for the TG/HDL-C ratio in children and adolescents could provide valuable information for individualized interpretations of lipid profiles and interventions as well as for strategies to prevent and manage childhood and adolescent dyslipidemia. PMID- 27373986 TI - Editorial Comment. PMID- 27373985 TI - The Superiority of Allogeneic Hematopoietic Stem Cell Transplantation Over Chemotherapy Alone in the Treatment of Acute Myeloid Leukemia Patients with Mixed Lineage Leukemia (MLL) Rearrangements. AB - BACKGROUND Acute myeloid leukemia (AML) patients with mixed lineage leukemia (MLL) gene rearrangements always had a very poor prognosis. In this study, we report the incidence of MLL rearrangements in AML patients using gene analysis, as well as the clinical significance and prognostic features of these rearrangements. MATERIAL AND METHODS This retrospective study took place from April 2008 to November 2011 in the People's Liberation Army General Hospital. A total 433 AML patients were screened by multiple nested reverse transcription polymerase chain reaction (RT-PCR) to determine the incidence of the 11 MLL gene rearrangements. There were 68 cases of MLL gene rearrangements, for a positive rate of 15.7%. A total of 24 patients underwent allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and 34 patients received at least 4 cycles of chemotherapy. Ten patients were lost to follow-up. RESULTS The median follow-up was 29 months. The complete remission (CR) rate was 85.4%. The overall survival (OS) was 57.4+/-5.9 months for the Allo-HSCT group and 21.0+/-2.1 months for the chemotherapy group. The Allo-HSCT group had superior survival compared with the chemotherapy group (5-year OS: 59+/-17% vs. 13+/-8%, P<0.01; 5-year disease-free survival [DFS]: 65+/-10% vs. 40+/-16%, P>0.05). Multivariate analysis showed that transplantation, platelets >50*10^9/L at onset, and CR are associated with a better OS in MLL rearranged AML patients. Patients with thrombocytopenia and extramedullary involvement were prone to relapse. CONCLUSIONS Our results suggest that Allo-HSCT is superior to chemotherapy alone for treating MLL rearranged AML patients. Patients treated with Allo-HSCT have a better prognosis and a longer survival. CR is an independent prognostic factor for OS, and extramedullary involvement is an independent prognostic factor for DFS. MLL rearranged AML patients with thrombocytopenia at onset <50*10^9 had very bad OS and DFS. PMID- 27373987 TI - Knockdown of TAZ modifies triple-negative breast cancer cell sensitivity to EGFR inhibitors by regulating YAP expression. AB - Triple-negative breast cancer (TNBC) constitutes ~10-15% of breast cancer patients and represents an aggressive subtype with poor overall prognosis. TNBC is an important clinical challenge because it does not respond well to endocrine therapy and have a higher rate of early recurrence and distant metastasis following chemotherapy. Although it has been reported that the epidermal growth factor receptor (EGFR) was overexpressed in ~80% of TNBC, anti-EGFR therapy showed limited clinical benefit according to phase II studies. In this study, we first observed that knockdown of the transcriptional coactivator with PDZ-binding domain (TAZ) gene can regulate the sensitivity of TNBC cell lines to EGFR inhibitors (EGFRI) in a cell context-depended manner. Furthermore, in certain breast cancer cell lines the YES-associated protein, paralog of TAZ (YAP) expression can be upregulated by TAZ inhibition which leads to EGFRI resistance. These results suggest a specific inhibitor to TAZ/YAP combined with anti-EGFR therapy may prove effective and provide a reason why targeting EGFR showed limited clinical benefit in TNBC treatment. PMID- 27373988 TI - Association Between Asthma and Sensitization to Allergens of Dermatophagoides pteronyssinus. AB - BACKGROUND AND OBJECTIVE: Little is known about the role of molecular diagnosis in house dust mite (HDM) allergy. In this study, we investigated the association between the sensitization profile of adolescent and adult HDM-allergic patients and asthma in a region with high rates of exposure to HDM. METHODS: We conducted a cross-sectional study of 384 HDM-allergic patients (38.5%, males; median age, 28 years). A total of 368 patients (95.8%) had rhinitis, and 175 (45.6%) had asthma. Specific IgE (sIgE) to Dermatophagoides pteronyssinus, nDer p 1, rDer p 2, and rPen a 1 was measured in all patients. sIgE to Lepidoglyphus destructor was measured in patients (n=301) with a positive skin test result. RESULTS: Significantly higher concentrations of sIgE to Der p 1 and sIgE to Der p 2 were observed in patients with asthma than in those without asthma. The proportion of asthmatic patients was higher among individuals who reacted (>=0.35 kUA/L) to both Der p 1 and Der p 2 (147/291, 50.5%) than among those who reacted to only 1 allergen (either Der p 1 or Der p 2, 18/55, 32.7%) or neither allergen (10/38, 26.3%, P=.002). Reactivity to both allergens was associated with asthma after adjusting for age and sex (OR, 2.87; 95%CI, 1.32-6.20). Higher concentrations of sIgE to L destructor were observed in patients with asthma than in patients without asthma. Tropomyosin sIgE >=0.35 kUA/L was detected in only 6 individuals (1.6%). CONCLUSIONS: L destructor may be a relevant allergen in high-exposure areas. Dual sensitization (ie, IgE to both Der p 1 and Der p 2) may help to identify HDM-allergic patients who are at risk of asthma. PMID- 27373989 TI - Bullous pemphigoid-like skin blistering disease in a rhesus macaque (Macaca mulatta). AB - Autoimmune bullous disease is very uncommon in non-human primates. We observed a bullous skin disease in a male rhesus monkey while conducting porcine islet xenotransplantation. Fifty days after the transplantation, multiple bullous skin lesions were observed. There was no mucosal involvement. Skin biopsy results demonstrated a subepidermal blister with no necrotic keratinocytes. Immunofluorescent staining showed linear IgG deposition at the roof of the blister. These skin lesions spontaneously disappeared. Considering these results, this monkey was diagnosed with bullous pemphigoid (BP). As far as we know, this is the first report of BP in non-human primates. PMID- 27373990 TI - Parenchymal Airspace Profiling: Sensitive Quantification and Characterization of Lung Structure Evaluating Parenchymal Destruction. AB - Lung morphometry was introduced over 50 years ago to provide quantitative evaluation of the lung structure. The existing parameters, such as mean linear intercept and destructive index, suffer from simplistic data interpretation and a subjective data acquisition process. To overcome these existing shortcomings, parenchymal airspace profiling (PAP) was developed to provide a more detailed and unbiased quantitative method. Following the standard protocols of fixation, embedding, and sectioning, lung micrographs were: (1) marked with nonparenchymal area, preprocessed, and binarized under the researcher's supervision; (2) analyzed with a statistical learning method, Gaussian mixture model, to provide an unbiased categorization of parenchymal airspace compartments, corresponding to a single alveolus, alveolar sac, and ductal/destructive airspace; and (3) further quantified into morphometric parameters, including reference volume, alveolar count, and ductal/destructive fraction (DF) based on stereological principles. PAP was performed on hematoxylin and eosin-stained lung sections from mice and rabbits. Unbiased categorization revealed differences in alveolar size among several mouse strains (NZW/LacJ 0.05; no numerical results provided) compared to conventional rehabilitation. The study did not measure pain score, HRQOL, global assessment of treatment success, hip dislocation, re-operation rate or total adverse events. AUTHORS' CONCLUSIONS: Very low quality evidence is available from single trials, thus we are uncertain if hip precautions with or without the addition of equipment and functional restrictions are effective in preventing dislocation and improving outcomes after THA. There is also insufficient evidence to support or refute the adoption of a postoperative community rehabilitation programme consisting of functional reintegration and education compared to conventional rehabilitation strategies based on functional outcomes.Further high-quality trials are warranted to assess the outcomes of different occupational therapy interventions both in the short and longer-term for those who undergo THA. An assessment of the impact of such interventions on pain and restriction on personal ADL, EADL and instrumental ADL is needed, and also of functional integration-type interventions rather than just hip precautions, equipment and restrictions. PMID- 27374002 TI - Between exclusion and emancipation: Foucault's ethics and disability. AB - The aim of the study was to demonstrate how Foucault's ethics, which we understand as a tension between exclusion and emancipation, helps both critically reassess two disability models that prevail in the contemporary literature concerning disability, that is the medical model and the social one, and support and inspire an ethical project of including people with disabilities in spheres of life from which they have been excluded by various power/knowledge regimes. We claim, following Foucault, that such a project should be informed by critical reflection on exclusion-generating forms of knowledge about people with disabilities and focused on individual ethical actions fostering self-realization and emancipation of people with disability. PMID- 27374004 TI - Mortality and Rates of Graft Rejection or Failure Following Intestinal Transplantation in Patients With vs Without Crohn's Disease. AB - BACKGROUND & AIMS: Treatment of Crohn's disease (CD) may require multiple bowel resections that lead to short bowel syndrome. Intestinal transplantation is an effective treatment for short bowel syndrome, but limited data are available on long-term outcomes in CD. We aimed to characterize the long-term risk of rejection, graft failure, and death among patients with CD after intestinal transplantation, and compare their outcomes with those of patients without CD. METHODS: We performed a retrospective study of adults in the Scientific Registry of Transplant Recipients who received intestinal transplants in the United States from May 1990 through June 2014. Outcomes data were collected at 3 months, 6 months, 1 year, and every year after the procedure. We compared risks of rejection at 1 year after transplantation between patients with and without CD using the chi-square test and logistic regression. Longitudinal risks of graft failure and death were compared between patients with and without CD using the Kaplan-Meier method and Cox proportional hazards. Multivariable analyses adjusted for recipient, donor, and institutional characteristics. RESULTS: Of 1115 cases of intestinal transplantation, 142 were performed for CD and 973 for non-CD indications. One year after the procedure, the transplant was rejected in 36.9% of patients with CD and 33.3% of patients without CD (P = .48). For patients with CD, the actuarial risk of graft failure at 1, 5, and 10 years after intestinal transplantation was 18.6%, 38.7%, and 49.2%; the risk of death was 22.5%, 50.3%, and 59.7%, respectively. The risk of graft failure was greater for patients with CD (adjusted hazard ratio [aHR], 1.48; 95% CI, 1.03-2.13; P = .04), but patients with versus without CD had similar risks of death (aHR, 0.88; 95% CI, 0.64-1.20; P = .41). In subgroup analyses, the risk of graft failure was increased among patients with CD undergoing transplantation between 1990 and 2000 (aHR, 3.49; 95% CI, 1.23-9.92; P = .02), but not after 2000 (aHR, 1.37; 95% CI, 0.92-2.04; P = .12). CONCLUSIONS: In an analysis of patients who received intestinal transplants, the risks of graft rejection or death were similar between patients with versus without CD. Before year 2000, patients with CD had an increased risk of graft failure, but not thereafter. Changes in posttransplant immunosuppression around the same time might be analyzed to learn more about the mechanisms and management strategies to reduce graft failure in CD. PMID- 27374005 TI - Esophagitis Caused by Cytomegalovirus Infection in an Immune-competent Patient. PMID- 27374003 TI - Patients With Hepatocellular Carcinoma Have Highest Rates of Wait-listing for Liver Transplantation Among Patients With End-Stage Liver Disease. AB - BACKGROUND & AIMS: Despite recent attention to differences in access to livers for transplantation, research has focused on patients already on the wait list. We analyzed data from a large administrative database that represents the entire US population, and state Medicaid data, to identify factors associated with differences in access to wait lists for liver transplantation. METHODS: We performed a retrospective cohort study of transplant-eligible patients with end stage liver disease using the HealthCore Integrated Research Database (2006-2014; n = 16,824) and Medicaid data from 5 states (2002-2009; California, Florida, New York, Ohio, and Pennsylvania; n = 67,706). Transplant-eligible patients had decompensated cirrhosis, hepatocellular carcinoma (HCC), and/or liver synthetic dysfunction, based on validated International Classification of Diseases, Ninth Revision-based algorithms and data from laboratory studies. Placement on the wait list was determined through linkage with the Organ Procurement and Transplantation Network database. RESULTS: In an unadjusted analysis of the HealthCore database, we found that 29% of patients with HCC were placed on the 2 year wait list (95% confidence interval [CI], 25.4%-33.0%) compared with 11.9% of patients with stage 4 cirrhosis (ascites) (95% CI, 11.0%-12.9%) and 12.6% of patients with stage 5 cirrhosis (ascites and variceal bleeding) (95% CI, 9.4% 15.2%). Among patients with each stage of cirrhosis, those with HCC were significantly more likely to be placed on the wait list; adjusted subhazard ratios ranged from 1.7 (for patients with stage 5 cirrhosis and HCC vs those without HCC) to 5.8 (for patients with stage 1 cirrhosis with HCC vs those without HCC). Medicaid beneficiaries with HCC were also more likely to be placed on the transplant wait list, compared with patients with decompensated cirrhosis, with a subhazard ratio of 2.34 (95% CI, 2.20-2.49). Local organ supply and wait list level demand were not associated with placement on the wait list. CONCLUSIONS: In an analysis of US healthcare databases, we found patients with HCC to be more likely to be placed on liver transplant wait lists than patients with decompensated cirrhosis. Previously reported reductions in access to transplant care for wait-listed patients with decompensated cirrhosis underestimate the magnitude of this difference. PMID- 27374006 TI - Gastrointestinal Manifestations of Autosomal-Dominant Polycystic Kidney Disease. AB - Autosomal-dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease, and the fourth most common cause of end-stage renal disease. ADPKD is a systemic disorder, associated with numerous extrarenal manifestations, including polycystic liver disease, the most common gastrointestinal manifestation, and diverticular disease, inguinal, and ventral hernias, pancreatic cysts, and large bile duct abnormalities. All of these gastrointestinal manifestations play a significant role in disease burden in ADPKD, particularly in the later decades of life. Thus, as ADPKD becomes more recognized, it is important for gastroenterologists to be knowledgeable of this monogenic disorder's effects on the digestive system. PMID- 27374007 TI - Epithelial Thickness is a Marker of Gastroesophageal Reflux Disease. AB - BACKGROUND & AIMS: Histologic criteria have been refined for the diagnosis of gastroesophageal reflux disease (GERD). We aimed to evaluate these criteria for the assessment of GERD and to measure interassessor agreement. METHODS: We performed a post hoc analysis of data from the Diamond study (NCT 00291746), conducted in Europe and Canada on adults with frequent upper gastrointestinal symptoms who had not taken a proton pump inhibitor in the previous 2 months. GERD was diagnosed based on the presence of 1 or more of the following: reflux esophagitis, pathologic esophageal acid exposure, and/or positive symptom-acid association probability. Nonerosive reflux disease was defined as the presence of pathologic esophageal acid exposure and/or a positive symptom-acid association probability, but no reflux esophagitis. Biopsies collected from 336 patients from 0.5 cm and 2.0 cm above the Z line were evaluable; they were analyzed independently at pathology centers in Germany and Italy (biopsies from 258 and 195 patients, respectively). The primary outcomes were the accuracy of histologic criteria for the diagnosis of GERD, defined by endoscopy and pH monitoring, and interassessor agreement on histologic criteria. RESULTS: At the assessment site for basal cell layer thickness, total epithelial thickness was the best performing criterion for diagnosis of investigation-defined GERD; it also identified nonerosive reflux disease, reflux esophagitis, and pathologic esophageal acid exposure at 0.5 cm and 2.0 cm above the Z line. Basal cell layer thickness and presence of dilated intercellular spaces did not identify patients with GERD. Among the criteria tested, the best agreement between assessments carried out at the 2 pathology centers was for total epithelial thickness at 0.5 cm and 2.0 cm above the Z line. CONCLUSIONS: Based on an analysis of 336 patients with frequent upper gastrointestinal symptoms, total epithelial thickness is a robust histologic marker for GERD. PMID- 27374008 TI - A Multifunctional Mn(II) Phosphonate for Rapid Separation of Methyl Orange and Electron-Transfer Photochromism. AB - A Mn(II) phosphonate of the general formula [Mn(H2 L)2 (H2 O)2 (H2 bibp)] adopts a layered motif with protonated H2 bibp(2+) cations embedded in the channels (H4 L=thiophene-2-phosphonic acid; bibp=4,4'-bis(1-imidazolyl)biphenyl). The title compound exhibits excellent adsorptive removal of methyl orange (MO) dye from aqueous solution. Its advantageous features include fast adsorption, high uptake capacity, selective removal, and reusability, which are of great significance for practical application in wastewater treatment. Meanwhile, the compound displays rapid photochromism upon irradiation with visible light at room temperature. Extensive research has demonstrated that such behavior is based on a ligand-to ligand charge-transfer (LLCT) mechanism. The irradiated sample possesses an ultra long-lived charge-separated state. Moreover, not only is the compound the first Mn-based photochromic MOF, but it is also one of the very few examples showing LLCT with non-photochromic components. PMID- 27374010 TI - Littoral cell angioma of the spleen: a study of 25 cases with confirmation of frequent association with visceral malignancies. AB - AIMS: Littoral cell angioma (LCA) is a rare primary splenic tumour that is frequently associated with internal malignancies. Immunohistochemistry can demonstrate a distinct hybrid endothelial-histiocytic phenotype of littoral cells, and is a helpful adjunct for making the correct diagnosis. The aims of this study were to present a series of 25 LCAs, with an emphasis on the frequent association of the neoplasm with visceral malignancies, and to provide a detailed immunohistochemical analysis by employing new markers. METHODS AND RESULTS: All 25 cases with available tissue blocks were immunohistochemically stained for endothelial and histiocytic markers. Clinical and follow-up data were retrieved from the respective institutions. The tumours were obtained from 16 males and nine females, whose age ranged from 32 to 86 years (mean 56.2 years). Clinical information was available for 24 of 25 patients, and follow-up for 11 of 25 patients (range 2-19 years; mean 11.6 years). Immunohistochemically, all cases were positive for LYVE-1, factor VIII, FLI-1, vascular endothelial growth factor receptor (VEGFR)-2, VEGFR-3, claudin-5, ERG, LMO2, CD31, CD163, lysozyme, and CD4, but negative for D2-40, CD8, and factor XIIIa. Fifteen of 25 cases were associated with various malignancies, including epithelial, mesenchymal and haematological tumours. CONCLUSIONS: The cohort of 25 patients is the largest series of LCAs published to date. By using antibodies against recently introduced endothelial markers, we have expanded the immunoprofile of LCA. We have further highlighted the clinical significance of LCA, as more than half of the patients in this study also harboured a coexisting visceral malignancy. Therefore, we conclude that the finding of splenic LCA mandates a thorough clinical evaluation for a concomitant malignancy. PMID- 27374011 TI - Hip Strength Deficits in People With Symptomatic Knee Osteoarthritis: A Systematic Review With Meta-analysis. AB - Study Design Systematic review with meta-analysis. Background A complete understanding of impairments associated with knee osteoarthritis would optimize exercise interventions for people with knee osteoarthritis. Our current understanding of hip strength deficits in this population is based on studies with conflicting findings and small samples. There is a need to systematically review and pool current evidence. Objectives To determine whether hip strength deficits exist in people with symptomatic knee osteoarthritis. Methods Electronic databases (MEDLINE, CINAHL, Embase, the Cochrane Library, and PsycINFO) were searched through February 2016. Studies comparing hip strength in people diagnosed with symptomatic knee osteoarthritis to healthy control participants were included in the review. A meta-analysis with random effects was applied to relevant data from included studies and a modified Grading of Recommendations Assessment, Development and Evaluation approach was used to evaluate the quality of evidence for each pooled analysis. Results Five studies were included in the review. Meta-analysis revealed moderate-quality evidence of weaker isometric and isokinetic hip abduction strength in people with knee osteoarthritis (moderate difference: 7% to 24% weaker) and very low-quality evidence of no difference in isometric hip adduction strength. There was very low- to moderate-quality evidence of weaker isokinetic hip strength in the remaining planes of motion (moderate to large differences: 14% to 55% weaker). Conclusion Significant hip strength deficits exist in people with knee osteoarthritis. Hip strength assessment should be considered in clinical practice and may assist with directing targeted management strategies. Level of Evidence Symptom prevalence, level 1a-. J Orthop Sports PhysTher 2016;46(8):629-639. Epub3 Jul 2016. doi:10.2519/jospt.2016.6618. PMID- 27374009 TI - Molecular characterization and analysis of high-level multidrug-resistance of Shigella flexneri serotype 4s strains from China. AB - To conduct the first comprehensive analysis of Shigella flexneri serotype 4s, a novel serotype found in 2010, we identified 24 serotype 4s isolates from 1973 shigellosis cases in China (2002-2014). The isolates were characterized by single nucleotide polymorphism (SNP) phylogenetic analysis, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) to determine their genetic relatedness, and analysed further for their antimicrobial susceptibilities and antimicrobial resistance determinants. The PFGE and SNP phylogenetic analyses suggest that S. flexneri serotype 4s strains are derived from multiple serotypes, including two predominant serotypes in China: serotype X variant and serotype II. Three new sequence types were identified by MLST. All isolates were resistant to ticarcillin, ampicillin and tetracycline, with high level resistance to third-generation cephalosporins. Notably, all the isolates were multidrug resistant (MDR), with the highest levels of resistance observed for eight antimicrobials classes. Most isolates contain various antimicrobial resistance determinants. In conclusion, we found that serotype 4s isolates have multiple evolutionary sources, diverse biochemical characteristics and genomes, and highly prevalent multidrug resistance and antimicrobial-resistant determinants. With few clinical treatment options, continuous monitoring and timely intervention against this emerging MDR serotype is essential. The possibility that serotype 4s will become the next predominant serotype exists. PMID- 27374012 TI - Pain During Prolonged Sitting Is a Common Problem in Persons With Patellofemoral Pain. AB - Study Design Retrospective cohort. Background Although persons with patellofemoral pain (PFP) often report pain with prolonged sitting, little is known about the prevalence and characteristics of sitting pain. Objectives To describe the proportion of persons with PFP who experience problems with prolonged sitting and to determine patient characteristics associated with sitting pain. Methods Four hundred fifty-eight participants with a diagnosis of PFP from 4 separate studies were included. Item 8 of the Anterior Knee Pain Scale was used to define the presence of problems with prolonged sitting with knee flexion, based on 3 categories: (1) "no difficulty," (2) "pain after exercise," or (3) "problems with prolonged sitting." Differences in demographic and clinical variables between categories were evaluated using Kruskal-Wallis tests (P<.05). Results Two hundred forty-nine (54.4% of the study sample) participants reported problems with prolonged sitting, and 121 (26.4%) reported sitting pain after exercise. Compared to those with no difficulty sitting (n = 88), participants classified as having problems with prolonged sitting were significantly younger (P = .038), more likely to be female (P = .033), had a lower body mass index (P = .027), reported higher pain severity (P<.001) and lower Anterior Knee Pain Scale scores (P<.001), and more frequently reported problems with squatting (P<.001). Conclusion Problems with prolonged sitting are evident in more than half of persons with PFP. Findings highlight the need to identify and adequately manage PFP associated with prolonged sitting. Further research should explore mechanisms of sitting pain and evaluate targeted interventions to reduce PFP with prolonged sitting. Level of Evidence Symptom prevalence study, level 2b. J Orthop Sports Phys Ther 2016;46(8):658-663. Epub 3 Jul 2016. doi:10.2519/jospt.2016.6470. PMID- 27374013 TI - Impaired Foot Plantar Flexor Muscle Performance in Individuals With Plantar Heel Pain and Association With Foot Orthosis Use. AB - Study Design Controlled laboratory study. Background Plantar heel pain is one of the most common foot and ankle conditions seen in clinical practice, and many individuals continue to have persisting or recurrent pain after treatment. Impaired foot plantar flexor muscle performance is a factor that may contribute to limited treatment success, but reliable methods to identify impairments in individuals with plantar heel pain are needed. In addition, foot orthoses are commonly used to treat this condition, but the implications of orthosis use on muscle performance have not been assessed. Objectives To assess ankle plantar flexor and toe flexor muscle performance in individuals with plantar heel pain using clinically feasible measures and to examine the relationship between muscle performance and duration of foot orthosis use. Methods The rocker-board plantar flexion test (RBPFT) and modified paper grip test for the great toe (mPGTGT) and lesser toes (mPGTLT) were used to assess foot plantar flexor muscle performance in 27 individuals with plantar heel pain and compared to 27 individuals without foot pain who were matched according to age, sex, and body mass. Pain ratings were obtained before and during testing, and self-reported duration of foot orthosis use was recorded. Results Compared to the control group, individuals with plantar heel pain demonstrated lower performance on the RBPFT (P = .001), the mPGTGT (P = .022), and the mPGTLT (P = .037). Longer duration of foot orthosis use was moderately correlated to lower performance on the RBPFT (r = 0.52, P = .02), the mPGTGT (r = -0.54, P = .01), and the mPGTLT (r = -0.43, P = .03). Conclusion Ankle plantar flexor and toe flexor muscle performance was impaired in individuals with plantar heel pain and associated with longer duration of self-reported foot orthosis use. J Orthop Sports Phys Ther 2016;46(8):681-688. Epub 3 Jul 2016. doi:10.2519/jospt.2016.6482. PMID- 27374014 TI - Rehabilitation and Return to Sport Following Surgical Repair of the Rectus Abdominis and Adductor Longus in a Professional Basketball Player: A Case Report. AB - Study Design Case report. Background Acute traumatic avulsion of the rectus abdominis and adductor longus is rare. Chronic groin injuries, often falling under the athletic pubalgia spectrum, have been reported to be more common. There is limited evidence detailing the comprehensive rehabilitation and return to sport of an athlete following surgical or conservative treatment of avulsion injuries of the pubis or other sports-related groin pathologies. Case Description A 29-year-old National Basketball Association player sustained a contact injury during a professional basketball game. This case report describes a unique clinical situation specific to professional sport, in which a surgical repair of an avulsed rectus abdominis and adductor longus was combined with a multimodal impairment- and outcomes-based rehabilitation program. Outcomes The patient returned to in-season competition at 5 weeks postoperation. Objective measures were tracked throughout rehabilitation and compared to baseline assessments. Measures such as the Copenhagen Hip and Groin Outcome Score and numeric pain rating scale revealed progress beyond the minimal important difference. Discussion This case report details the clinical reasoning and evidence-informed interventions involved in the return to elite sport. Detailed programming and objective assessment may assist in achieving desired outcomes ahead of previously established timelines. Level of Evidence Therapy, level 4. J Orthop Sports Phys Ther 2016;46(8):697-706. Epub 3 Jul 2016. doi:10.2519/jospt.2016.6352. PMID- 27374015 TI - Postural Stability During Single-Leg Stance: A Preliminary Evaluation of Noncontact Lower Extremity Injury Risk. AB - Study Design Controlled laboratory study with a prospective cohort design. Background Postural stability deficits during single-leg stance have been reported in persons with anterior cruciate ligament (ACL) injury, ACL reconstruction, and chronic ankle instability. It remains unclear whether impaired postural stability is a consequence or cause of these injuries. Objectives To prospectively investigate whether postural stability deficits during single-leg stance predict noncontact lower extremity injuries. Methods Fifty injury-free female athletes performed a transition task from double-leg stance to single-leg stance with eyes closed. Center-of-pressure displacement, the main outcome variable, was measured during the first 3 seconds after the time to a new stability point was reached during single-leg stance. Noncontact lower extremity injuries were recorded at a 1-year follow-up. Results Six participants sustained a noncontact ACL injury or ankle sprain. Center-of-pressure displacement during the first 3 seconds after the time to a new stability point was significantly increased in the injured (P = .030) and noninjured legs (P = .009) of the injured group compared to the respective matched legs of the noninjured group. The area under the receiver operating characteristic curve (AUC) analysis revealed significant discriminative accuracy between groups for the center-of-pressure displacement during the first 3 seconds after the time to a new stability point of the injured (AUC = 0.814, P = .015) and noninjured legs (AUC = 0.897, P = .004) of the injured group compared to the matched legs of the noninjured group. Conclusion This preliminary study suggests that postural stability measurements during the single-leg stance phase of the double- to single-leg stance transition task may be a useful predictor of increased risk of noncontact lower extremity injury. Further research is indicated. Level of Evidence Prognosis, level 4. J Orthop Sports PhysTher 2016;46(8):650-657. Epub 3 Jul 2016. doi:10.2519/jospt.2016.6278. PMID- 27374016 TI - Satisfaction With the Outcome of Physical Therapist-Prescribed Exercise in Chronic Whiplash-Associated Disorders: Secondary Analysis of a Randomized Clinical Trial. AB - Study Design Secondary analysis of a randomized clinical trial. Background Patient perception of the benefits gained from treatment is important, yet satisfaction with the outcome of treatment for chronic whiplash-associated disorders (WADs) has not been investigated. Objectives To investigate whether satisfaction with the outcome of treatment for chronic WAD changed over time, and whether there were group differences. Methods Two hundred sixteen people with chronic WAD (66% women; mean age, 40.4 years) participated in a 3-month program of physical therapist-led neck-specific exercises with or without a behavioral approach, or received a prescription of general physical activity. The main outcome was satisfaction with the outcome of treatment, assessed at baseline and 3, 6, and 12 months later. Additional outcomes were enablement and expectation fulfillment. Results Satisfaction improved over time in the 3 groups (odds ratio = 1.15; 95% confidence interval: 1.10, 1.20; P<.001). There was a significant group-by-time interaction (P<.001), with increased odds of being satisfied in the groups receiving neck-specific exercises compared to general physical activity. Enablement increased after completion of the intervention in all groups (P<.001). People who received neck-specific exercises reported greater enablement and expectation fulfillment than people prescribed general physical activity (P<.01). Conclusion Exercise interventions for chronic WAD led to increased satisfaction for 12 months following treatment that was unrelated to the type of exercise intervention received. Level of Evidence Therapy, level 1b. Registered January 22, 2012 at www.ClinicalTrials.gov (NCT01528579). J Orthop Sports Phys Ther 2016;46(8):640-649. Epub 3 Jul 2016. doi:10.2519/jospt.2016.6136. PMID- 27374018 TI - Moving pictures: Highlights 2016 open for submissions. PMID- 27374017 TI - The Accuracy of the VISA-P Questionnaire, Single-Leg Decline Squat, and Tendon Pain History to Identify Patellar Tendon Abnormalities in Adult Athletes. AB - Study Design Cross-sectional clinical assessment. Background Patellar tendinopathy is not always accompanied by patellar tendon abnormalities (PTAs). Thus, clinical screening tools to help identify patients with patellar tendon pain who have PTAs could enhance clinical decision making and patient prognosis. Objectives To test the diagnostic accuracy of the Victorian Institute of Sport Assessment-Patella (VISA-P) questionnaire, a single-leg decline squat (SLDS), tendon pain history, age, and years of sports participation to identify athletes with symptomatic patellar tendons who have PTAs confirmed on imaging. Methods Data provided by ultrasound examination, the VISA-P questionnaire, the SLDS, tendon pain history, age, and years of sport participation were collected in 43 athletes. A classification and regression tree (CART) model was developed to verify variables associated with PTA occurrence. Likelihood ratios (LRs) were computed for positive and negative tests. Results The SLDS, VISA-P questionnaire, and tendon pain history were associated with PTA occurrence. Athletes with negative results on all 3 tests (CART model) had a lower likelihood of having PTAs (negative LR = 0.3; 95% confidence interval [CI]: 0.2, 0.5). The isolated use of the SLDS or tendon pain history (positive LR = 4.2; 95% CI: 2.3, 7.14 and 4.5; 95% CI: 1.8, 11.1, respectively) had similar influence on probability of PTA presence compared to the CART model (positive LR = 4.1; 95% CI: 2.5, 6.3). Conclusion Although the objective was to investigate a clinical test to identify PTAs, the combined use of the tests had greater accuracy to identify individuals without PTAs. Level of Evidence Diagnosis, level 3b. J Orthop Sports Phys Ther 2016;46(8):673-680. Epub 3 Jul 2016. doi:10.2519/jospt.2016.6192. PMID- 27374019 TI - Chemical complexity of the urban atmosphere and its consequences: general discussion. PMID- 27374020 TI - Are intra-articular injections of hyaluronic acid effective for the treatment of temporomandibular disorders? A systematic review. AB - This systematic review aimed to investigate whether intra-articular injections of hyaluronic acid (HA) are better than other drugs used in temporomandibular joint arthrocentesis, for the improvement of temporomandibular disorder (TMD) symptoms. Two independent reviewers performed an electronic search of the MEDLINE and Web of Science databases for relevant studies published in English up to March 2016. The key words used included a combination of 'hyaluronic acid', 'viscosupplementation', 'intra-articular injections', 'corticosteroids', or 'non steroidal anti inflammatory agents' with 'temporomandibular disorder'. Selected studies were randomized clinical trials and prospective or retrospective studies that primarily investigated the application of HA injections compared to other intra-articular medications for the treatment of TMD. The initial screening yielded 523 articles. After evaluation of the titles and abstracts, eight were selected. Full texts of these articles were accessed and all fulfilled the inclusion criteria. Intra-articular injections of HA are beneficial in improving the pain and/or functional symptoms of TMDs. However, other drug therapies, such as corticosteroid and non-steroidal anti-inflammatory drug injections, can be used with satisfactory results. Well-designed clinical studies are necessary to identify an adequate protocol, the number of sessions needed, and the appropriate molecular weight of HA for use. PMID- 27374021 TI - Reflective and collaborative skills enhances Ambulance nurses' competence - A study based on qualitative analysis of professional experiences. AB - BACKGROUND: The Swedish ambulance health care services are changing and developing, with the ambulance nurse playing a central role in the development of practice. The competence required by ambulance nurses in the profession remains undefined and provides a challenge. The need for a clear and updated description of ambulance nurses' competence, including the perspective of professional experiences, seems to be essential. AIM: The aim of this study was to elucidate ambulance nurses' professional experiences and to describe aspects affecting their competence. METHODS: For data collection, the study used the Critical Incident Technique, interviewing 32 ambulance nurses. A qualitative content analysis was applied. RESULTS AND CONCLUSION: This study elucidates essential parts of the development, usage and perceptions of the competence of ambulance nurses and how, in various ways, this is affected by professional experiences. The development of competence is strongly affected by the ability and possibility to reflect on practice on a professional and personal level, particularly in cooperation with colleagues. Experiences and communication skills are regarded as decisive in challenging clinical situations. The way ambulance nurses perceive their own competence is closely linked to patient outcome. The results of this study can be used in professional and curriculum development. PMID- 27374022 TI - Obesity and the Emergency Short Stay Unit. AB - OBJECTIVES: To evaluate the health service requirements of obese patients admitted to an Emergency Short Stay Unit (ESSU) and specifically compare length of stay (LOS), failure of ESSU management, and rates of investigations and allied health interventions among obese and non-obese patients. METHODS: A prospective cohort study, using convenience sampling was conducted. The body mass index (BMI) of participants was calculated and those with a BMI of ?30 were allocated to the obese group, and those that had a BMI of <30 to the non-obese group. Data collected included demographics, admission diagnosis, time and date of ESSU admission and discharge, discharge disposition, radiological investigations, and referrals made to allied health personnel during ESSU admission. RESULTS: There were 262 patients that were recruited sub-grouped into 127 (48.5%) obese participants and 135 (51.5%) non-obese participants with similar sex and diagnostic category distributions. The mean LOS in ESSU was similar - 11.5h (95% CI: 9.9-13.1) for obese patients and, 10.2h (95% CI: 8.8-11.6) for non-obese patients (p=0.21). Failure rates of ESSU management, defined as inpatient admission to hospital, were also similar with 29 (22.8%) obese patients admitted to hospital compared to 25 (18.5%) non-obese patients (p=0.39). Plain X-ray requests were significantly higher among obese patients (71.6 vs 53.3%; p=0.002), as was the rate of allied health interventions (p=0.001). CONCLUSION: There was no significant difference in inpatient admission rates or LOS between obese and non-obese patients managed in the ESSU. Provisions for increased rate of investigations and allied health interventions for obese patients may facilitate timely assessment and disposition from ESSU. PMID- 27374024 TI - Transition metal (Ti, Mo, Nb, W) nitride catalysts for lignin depolymerisation. AB - Metal nitrides are promising catalysts for depolymerisation of lignin in supercritical ethanol; cheap and abundant titanium nitride affords an aromatic monomer yield of 19 wt% from soda lignin. The reaction mechanism is discussed on the basis of the products and a guaiacol model compound study. PMID- 27374023 TI - Programmed activation of cancer cell apoptosis: A tumor-targeted phototherapeutic topoisomerase I inhibitor. AB - We report here a tumor-targeting masked phototherapeutic agent 1 (PT-1). This system contains SN-38-a prodrug of the topoisomerase I inhibitor irinotecan. Topoisomerase I is a vital enzyme that controls DNA topology during replication, transcription, and recombination. An elevated level of topoisomerase I is found in many carcinomas, making it an attractive target for the development of effective anticancer drugs. In addition, PT-1 contains both a photo-triggered moiety (nitrovanillin) and a cancer targeting unit (biotin). Upon light activation in cancer cells, PT-1 interferes with DNA re-ligation, diminishes the expression of topoisomerase I, and enhances the expression of inter alia mitochondrial apoptotic genes, death receptors, and caspase enzymes, inducing DNA damage and eventually leading to apoptosis. In vitro and in vivo studies showed significant inhibition of cancer growth and the hybrid system PT-1 thus shows promise as a programmed photo-therapeutic ("phototheranostic"). PMID- 27374025 TI - Trade-offs between predator avoidance and electric shock avoidance in hermit crabs demonstrate a non-reflexive response to noxious stimuli consistent with prediction of pain. AB - Arthropods have long been thought to respond to noxious stimuli by reflex reaction. One way of testing if this is true is to provide the animal with a way to avoid the stimulus but to vary the potential cost of avoidance. If avoidance varies with potential cost then a decision making process is evident and the behaviour is not a mere reflex. Here we examine the responses of hermit crabs to electric shock within their shell when also exposed to predator or non-predator odours or to no odour. The electric shocks start with low voltage but increase in voltage with each repetition to determine how odour affects the voltage at which the shell is abandoned. There was no treatment effect on the voltage at which hermit crabs left their shells, however, those exposed to predator odours were less likely to evacuate their shells compared with no odour or low concentrations of non-predator odour. However, highly concentrated non-predator also inhibited evacuation. The data show that these crabs trade-off avoidance of electric shock with predator avoidance. They are thus not responding purely by reflex and the data are thus consistent with predictions of pain but do not prove pain. PMID- 27374026 TI - Teriparatide in patients with osteoporosis and type 2 diabetes. AB - Despite evidence for higher fracture risk, clinical effects of osteoporosis treatments in type 2 diabetes (T2D) are largely unknown. Post hoc analyses of the DANCE observational study compared T2D patients and patients without diabetes to assess the effect of teriparatide, an osteoanabolic therapy on skeletal outcomes and safety. Patients included ambulatory men and women with osteoporosis receiving teriparatide 20MUg/day SQ up to 24months followed by observation up to 24months. Main outcome measures included nonvertebral fracture incidence comparing 0-6months with 6+ months of teriparatide, change from baseline in BMD and back pain severity, and serious adverse events. Analyses included 4042 patients; 291 with T2D, 3751 without diabetes. Treatment exposure did not differ by group. For T2D patients, fracture incidence was 3.5 per 100 patient-years during 0-6months treatment, and 1.6 during 6months to treatment end (47% of baseline, 95% CI 12-187%); during similar periods, for patients without diabetes, fracture incidence was 3.2 and 1.8 (57% of baseline, 95% CI 39-83%). As determinants of fracture outcome during teriparatide treatment, diabetes was not a significant factor (P=0.858), treatment duration was significant (P=0.003), and the effect of duration was not significantly different between the groups (interaction P=0.792). Increases in spine and total hip BMD did not differ between groups; increase in femoral neck BMD was greater in T2D patients than in patients without diabetes (+0.34 and +0.004g/cm(2), respectively; P=0.014). Back pain severity decreased in both groups. Teriparatide was well tolerated without new safety findings. In conclusion, during teriparatide treatment, reduction in nonvertebral fracture incidence, increase in BMD, and decrease in back pain were similar in T2D and non-diabetic patients. PMID- 27374028 TI - Surviving but not thriving: inconsistent responses of zooxanthellate jellyfish polyps to ocean warming and future UV-B scenarios. AB - Complex changes to UV radiation at the Earth's surface are occurring concurrently with ocean warming. Despite few empirical tests, jellyfish are hypothesised to be increasing in some parts of the world because they are robust to environmental stressors. Here we examine the effects of UV-B and ocean warming projections on zooxanthellate jellyfish polyps. We exposed Cassiopea sp. polyps to three levels of UV-B (future-low (1.43 Wm(2)), current (1.60 Wm(2)), future-high (1.77 Wm(2))) and two levels of temperature (current-day (25 degrees C) and future (28 degrees C)) over 6 weeks. The intensity of UV-B was varied throughout the day to mimic diel variation in UV-B irradiance. Polyp survival, asexual reproduction and YII were measured. In the current and future-high UV-B treatments, more polyps were produced in 25 degrees C than 28 degrees C. This pattern, however, was reversed under future-low UV-B conditions, where more polyps were produced at 28 degrees C. YII was highest under current summer conditions and future conditions of low UV-B and increased temperature. YII, however, was reduced under high UV-B conditions but was further reduced with warming. Our results suggest that although Cassiopea polyps may survive elevated UV-B and warming conditions, they are unlikely to thrive. If, however, UV-B radiation decreases then ocean warming may facilitate increases in Cassiopea populations. PMID- 27374027 TI - Current real-life use of vasopressors and inotropes in cardiogenic shock - adrenaline use is associated with excess organ injury and mortality. AB - BACKGROUND: Vasopressors and inotropes remain a cornerstone in stabilization of the severely impaired hemodynamics and cardiac output in cardiogenic shock (CS). The aim of this study was to analyze current real-life use of these medications, and their impact on outcome and on changes in cardiac and renal biomarkers over time in CS. METHODS: The multinational CardShock study prospectively enrolled 219 patients with CS. The use of vasopressors and inotropes was analyzed in relation to the primary outcome, i.e., 90-day mortality, with propensity score methods in 216 patients with follow-up data available. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were analyzed with linear mixed modeling. RESULTS: Patients were 67 (SD 12) years old, 26 % were women, and 28 % had been resuscitated from cardiac arrest prior to inclusion. On average, systolic blood pressure was 78 (14) and mean arterial pressure 57 (11) mmHg at detection of shock. 90-day mortality was 41 %. Vasopressors and/or inotropes were administered to 94 % of patients and initiated principally within the first 24 hours. Noradrenaline and adrenaline were given to 75 % and 21 % of patients, and 30 % received several vasopressors. In multivariable logistic regression, only adrenaline (21 %) was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p = 0.002). The result was independent of prior cardiac arrest (39 % of patients treated with adrenaline), and the association remained in propensity-score-adjusted analysis among vasopressor-treated patients (OR 3.0, 95 % CI 1.3, 7.2, p = 0.013); this was further confirmed by propensity score-matched analysis. Adrenaline was also associated, independent of prior cardiac arrest, with marked worsening of cardiac and renal biomarkers during the first days. Dobutamine and levosimendan were the most commonly used inotropes (49 % and 24 %). There were no differences in mortality, whether noradrenaline was combined with dobutamine or levosimendan. CONCLUSION: Among vasopressors and inotropes, adrenaline was independently associated with 90-day mortality in CS. Moreover, adrenaline use was associated with marked worsening in cardiac and renal biomarkers. The combined use of noradrenaline with either dobutamine or levosimendan appeared prognostically similar. PMID- 27374030 TI - [Clinical and biological prognostic factors in relapsed acute myeloid leukemia patients]. AB - BACKGROUND AND OBJECTIVE: Acute myeloid leukemia (AML) is the most frequent type of acute leukemia in adults. Despite recent advances in the characterization of pathogenesis of AML, the cure rates are under 40%, being leukemia relapse the most common cause of treatment failure. Leukaemia relapse occurs due to clonal evolution or clonal escape. In this study, we aimed to analyze the clinical and biological factors influencing outcomes in patients with AML relapse. PATIENTS AND METHODS: We included a total of 75 AML patients who experienced leukaemia relapse after achieving complete remission. We performed complete immunophenotyping and conventional karyotyping in bone marrow aspirates obtained at diagnosis and at leukemia relapse. RESULTS: Overall survival (OS) of the series was 3.7%+/-2.3, leukaemia progression being the most common cause of death. Patients relapsing before 12 months and those with adverse cytogenetic molecular risk had statistically significant worse outcomes. A percentage of 52.5 of patients showed phenotypic changes and 50% cytogenetic changes at relapse. We did not find significant clinical factors predicting clonal evolution. The presence of clonal evolution at relapse did not have a significant impact on outcome. CONCLUSIONS: Patients with relapsed AML have a dismal prognosis, especially those with early relapse and adverse cytogenetic-molecular risk. Clonal evolution with phenotypic and cytogenetic changes occurred in half of the patients without predictive clinical factors or impact on outcome. PMID- 27374029 TI - [Cuadruple concomitant non-bismuth therapy vs. classical triple therapy as first line therapy for Helicobacter pylori infection]. AB - BACKGROUND AND OBJECTIVE: In a previous study we found that the classical triple therapy for Helicobacter pylori (H. pylori) had low efficacy (under 70%) in our area. After this finding, in mid 2012 quadruple concomitant therapy started to be prescribed in our hospital. The aim of the present study is to compare the efficacy of classical triple therapy and quadruple concomitant therapy without bismuth. MATERIAL AND METHODS: Observational retrospective study of prescribed treatments between 1st January 2012 and 5th May 2014 and their efficacy. RESULTS: During the study period 510 patients were prescribed a first line therapy; in 179 cases (35,1%) the combination amoxiciline+clarithromicine+PPI was prescribed during 7-14 days, and 298 patients (58,4%) were treated with amoxicillin+clarithromycin+metronidazole+PPI for 10 days. The quadruple concomitant therapy had a higher efficacy than the classical triple therapy, both in an "intention to treat" (84.8% vs. 65.7%, P=.001) and "per protocol" (86.9% vs. 67.2%, P=.001) analysis. Triple therapy had a higher efficacy when it was prescribed for 10 days compared to 7 days (77.9% vs. 56.5%, P=.005 per "intention to treat" and 77.9% vs. 58.5%, P=.011 "per protocol"). When quadruple concomitant therapy was compared with classical triple therapy prescribed over 10 days no significant differences were found. CONCLUSIONS: In our setting, cuadruple concomitant therapy without bismuth has a high efficacy as first line therapy for H. pylori eradication, with much better results than classical triple therapy in the way that it is most widely prescribed (short courses of 7-day with a single dose of omeprazole). PMID- 27374031 TI - [Mobilization of peripheral blood stem cells with plerixafor in poor mobilizer patients]. AB - BACKGROUND AND OBJECTIVE: Poor mobilization of peripheral blood stem cells (CD34(+) cells) from bone marrow is a frequent reason for not reaching the autologous stem cell trasplantation (SCT) procedure in patients diagnosed with lymphoma or myeloma. Plerixafor, a reversible inhibitor of the binding of stromal cell-derived factor 1 to its cognate receptor CXCR4, has demonstrated a higher capacity for the mobilization of peripheral blood stem cells in combination with granulocyte colony stimulating factor (G-CSF) compared with G-CSF alone. For this reason, plerixafor is now indicated for poor mobilizer myeloma or lymphoma patients. Some studies have recently indicated that a pre-emptive strategy of plerixafor use during first mobilization, according to the number of CD34(+) mobilized cells in peripheral blood or to the harvested CD34(+) cells after first apheresis, could avoid mobilization failures and re-mobilizations, as well as the delay of autologous SCT. The aim of this consensus was to perform a review of published studies on pre-emptive strategy and to establish common recommendations for hospitals in Catalonia and Balearics on the use of pre-emptive plerixafor. METHODS: For the Consensus, physicians from participant hospitals met to review previous studies as well as previous own data about plerixafor use. The GRADE system was used to qualify the available evidence and to establish recommendations on the use of pre-emptive plerixafor. RESULTS AND CONCLUSIONS: After a review of the literature, the expert consensus recommended the administration of pre-emptive plerixafor for multiple myeloma or lymphoma patients with a CD34+ cell count lower than 10 cells/MUL in peripheral blood (measured in the morning of day 4 of mobilization with G-CSF or after haematopietic recovery in the case of mobilization with chemotherapy plus G-CSF). PMID- 27374033 TI - Major and Minor Duodenal Papilla Neuroendocrine Tumors in Type 1 Neurofibromatosis: Case Report. PMID- 27374032 TI - Skin photoprotective and antiageing effects of a combination of rosemary (Rosmarinus officinalis) and grapefruit (Citrus paradisi) polyphenols. AB - BACKGROUND: Plant polyphenols have been found to be effective in preventing ultraviolet radiation (UVR)-induced skin alterations. A dietary approach based of these compounds could be a safe and effective method to provide a continuous adjunctive photoprotection measure. In a previous study, a combination of rosemary (Rosmarinus officinalis) and grapefruit (Citrus paradisi) extracts has exhibited potential photoprotective effects both in skin cell model and in a human pilot trial. OBJECTIVE: We investigated the efficacy of a combination of rosemary (R. officinalis) and grapefruit (C. paradisi) in decreasing the individual susceptibility to UVR exposure (redness and lipoperoxides) and in improving skin wrinkledness and elasticity. DESIGN: A randomised, parallel group study was carried out on 90 subjects. Furthermore, a pilot, randomised, crossover study was carried out on five subjects. Female subjects having skin phototype from I to III and showing mild to moderate chrono- or photoageing clinical signs were enrolled in both studies. Skin redness (a* value of CIELab colour space) after UVB exposure to 1 minimal erythemal dose (MED) was assessed in the pilot study, while MED, lipoperoxides (malondialdehyde) skin content, wrinkle depth (image analysis), and skin elasticity (suction and elongation method) were measured in the main study. RESULTS: Treated subjects showed a decrease of the UVB- and UVA-induced skin alterations (decreased skin redness and lipoperoxides) and an improvement of skin wrinkledness and elasticity. No differences were found between the 100 and 250 mg extracts doses, indicating a plateau effect starting from 100 mg extracts dose. Some of the positive effects were noted as short as 2 weeks of product consumption. CONCLUSIONS: The long-term oral intake of NutroxsunTM can be considered to be a complementary nutrition strategy to avoid the negative effects of sun exposure. The putative mechanism for these effects is most likely to take place through the inhibition of UVR-induced reactive oxygen species and the concomitant inflammatory markers (lipoperoxides and cytokines) together with their direct action on intracellular signalling pathways. PMID- 27374034 TI - Standard of care and guidelines in prevention and diagnosis of venous thromboembolism: medico-legal implications. AB - Concerning recent Italian laws and jurisprudential statements, guidelines application involves several difficulties in clinical practice, regarding prevention, diagnosis and therapy of venous thromboembolism. International scientific community systematically developed statements about this disease in order to optimize the available resources in prophylaxis, diagnosis and therapy. Incongruous prevention, missed or delayed diagnosis and/or inadequate treatment of this disease can frequently give rise to medico-legal litigation. PMID- 27374035 TI - Red cell distribution width and chronic heart failure: prognostic role beyond echocardiographic parameters. AB - AIM: Red cell distribution width (RDW) is a measure of anisocytosis. Higher values are robustly associated to adverse outcome in several conditions, including chronic heart failure (HF). The present study aimed to compared its prognostic role with that of echocardiographic parameters in this kind of patients. METHODS: 32 stable and optimally treated chronic HF patients were enrolled. We excluded subjects suffering from valvular diseases or atrial fibrillation. They underwent blood sampling and echocardiographic examination. The primary endpoint of the study was cardiovascular death and/or HF hospitalization in the first year after enrolment. RESULTS: 49 patients reached the primary endpoint. RDW best cut-off at ROC curve was 14.45%. Univariate analysis associated mitral regurgitation grade, left ventricular ejection fraction (LVEF), posterior wall thickness (PWT), LV mass index, and RDW>14.45% to the primary endpoint. Multivariate regression analysis showed that LVEF, PWT, and RDW>14.45% predict the primary endpoint. Area under ROC curve was 0.808 for LVEF, 0.762 for NYHA class, and 0.761 for RDW. CONCLUSION: In chronic HF patients RDW is a better predictor of adverse outcome than several echocardiographic parameters associated to outcome itself (LV mass index, mitral regurgitation grade), predicts prognosis even adjusting for those parameters, age and NYHA class, and is associated to several echocardiographic measurements. In conclusion, RDW can expand our tool bag in order to better follow-up these patients. PMID- 27374036 TI - Left ventricular function in rheumatoid arthritis during anti-TNF-alpha treatment: a speckle tracking prospective echocardiographic study. AB - AIM: Rheumatoid arthritis (RA) shows a high risk for cardiovascular disease, including heart failure. Although TNF-alpha has been implicated in the pathogenesis of myocardial remodelling, TNF-alpha inhibition did not show any efficacy in patients with advanced heart failure and should be contraindicated in RA with cardiac complications. We aimed to assess global left ventricular (LV) systolic function using global longitudinal strain (GLS) as a measure of myocardial deformation, in a group of RA patients before and during anti-TNF alpha treatment. METHODS: 13 patients (female:male 7:6) affected by RA were prospectively followed for one year during anti TNF-alpha treatment. Every subject underwent echocardiography before starting anti-TNF-alpha drugs and after one year of treatment, to evaluate LV ejection fraction (EF), telediastolic diameter, telediastolic volume and global longitudinal strain (GLS) that was calculated using 2D speckle tracking as the mean GLS from three standard apical views (2, 3 and 4 -chambers). The patients showed a mean age of 43 years at RA onset (SD: 13) and a mean follow-up of 7.3 years (SD: 4.8). Steroid and methotrexate were used in 84.6% and 100%, respectively, in association with etanercept (6 cases), adalimumab (4 cases) and infliximab (3 cases). RESULTS: Patients globally showed a normal EF before and after one year of treatment (mean: 65% and 65.7%, respectively). GLS did not differ before or after anti-TNF alpha treatment (mean: -15.8% and -16.7%, respectively). CONCLUSION: Anti-TNF alpha treatment did not significantly modify myocardial contractility after 12 months. PMID- 27374037 TI - Current activities of Cardiovascular Rehabilitation in the ambulatory setting of the Lombardy Region. AB - In the present work, the current activities of Cardiovascular Rehabilitation and Prevention (CRP) in the ambulatory setting of the Lombardy Region (Italy) are described. Based on the 2012 Legislation, ambulatory CRP is delivered by means of three programme categories (MAC 6, 7, and 8) with different degrees of intensity. The patient evaluation of global cardiovascular/clinical risk, comorbidity, and disability is the cornerstone for MAC prescription. Following the organization of MAC activities, a survey on 327 patients was carried out by the regional network of the Italian Society of Cardiovascular Rehabilitation (GICR-IACPR). Globally, acute coronary syndromes (with or without coronary revascularization) constituted the main access group to CRP. More than 60% of patients displayed a condition of high risk, comorbidity, and disability. The outcome of ambulatory CRP by means of MAC 6 and 7 was satisfactory, while in the 'less intensive' MAC 8 patients with complete drug up-titration and achievement of secondary prevention targets were no more than 70%. PMID- 27374038 TI - Arterial hypertension: which targets in over-75-year people? AB - Arterial hypertension has always been considered the main risk factor in cardiovascular prevention. However, the goals of anti-hypertensive treatment (targets) in the elderly has long been under discussion. The results of the studies in favor of the hypothesis "the lower the better" than those that argue against the existence of the phenomenon of the J-curve, that is, the hypothesis according to which mortality increases to too low pressure values lower than 115/75 mmHg, are still controversial. However, in elderly patients the association between blood pressure lowering and increased cardiovascular events seems to depend on the general health status, that means the presence of comorbidity, frailty and / or disability. Recent data from the SPRINT study show that the benefit of an intensive blood pressure target (SBP <120 mmHg) compared to a usual target (SBP <140 mmHg), appears to be greater in the oldest hypertensive patients (>=75 years). The cardio-geriatric functional assessment can provide useful information to better stratify the elderly and to define more accurately the pressure targets, the choice is individual. PMID- 27374039 TI - Cardiovascular health of the elderly. AB - Within the Osservatorio Epidemiologico Cardiovascolare/Health Examination Survey 426 men and 376 women, ages 75-79 years, randomly selected from the general population were examined. Participation rate was 50%; within men 78% were hypertensives, 36% had high serum cholesterol, 28% were diabetics, 25% were obese; within women 81% were hypertensives, 55% had high cholesterol, 19% were diabetics, 37% were obese. Preventive actions at individual and community level are urgent, also at this age range. PMID- 27374040 TI - Hyperglycemia, hypoglycemia and glycemic variability in the elderly: a fatal triad? AB - Diabetes mellitus is one of the most important causes of cardiovascular morbidity and mortality; the incidence of chronic complications of diabetes appears to be closely related to the degree of hyperglycaemia. However, results of clinical trials showed that intensive treatment of hyperglycaemia prevents microvascular complications, but has little or no effect on the incidence of cardiovascular events. Different hypoglycaemic drugs show different effects on cardiovascular risk. However, those trials have shown a neutral effect on cardiovascular mortality. This paradoxical result could be explained with the frequent use, in the past, of glucose-lowering agents capable of increasing the risk of hypoglicemia, glycemic variability and weight gain. In conclusion, an adequate glycemic control, in particular in elderly patients, should be achieved, whenever possible, using agents not inducing hypogycemia, glucose fluctuations, and weight gain. In fact, hypoglycaemia and glucose variability should be considered as independent cardiovascular risk factors to a similar extent to hyperglycemia. In this article, the author will review literature supporting the hypothesis that hyperglycemia, hypoglycaemia and glycemic variability are a fatal triad capable of increasing morbidity and mortality in patients with diabetes mellitus. PMID- 27374041 TI - Aging clinical problems: a difficult balance between age and frailty. AB - Frailty is a common geriatric syndrome that embodies an elevated risk of catastrophic declines in health and function among older adults. Frailty is a condition associated with ageing with associated weakness, slowing, decreased energy, lower activity, and, when severe, unintended weight loss. As a population ages, a central focus of geriatricians and public health practitioners is to understand, and then beneficially intervene on, the factors and processes that put elders at such risk, especially the increased vulnerability to stressors (e.g. extremes of heat and cold, infection, injury, or even changes in medication) that characterizes many older adults. The syndrome of geriatric frailty is hypothesized to reflect impairments in the regulation of multiple physiologic systems, embodying a lack of resilience to physiologic challenges and thus elevated risk for a range of deleterious endpoints. The empirical assessment of geriatric frailty in individuals seeks to capture this or related features. PMID- 27374042 TI - Aspirin use for primary prevention in elderly patients. AB - The net clinical benefit of aspirin in primary prevention is uncertain as the reduction in occlusive events needs to be balanced against the increase in gastro intestinal and cerebral bleedings. The meta-analysis of ATT (Anti Thrombotic Trialists) Collaboration in 2009 showed that aspirin therapy in primary prevention was associated with 12% reduction in cardio-vascular events, due mainly to a reduction in non-fatal myocardial infarction (0.18% vs 0.23% per year, p<0.0001). However, the benefit in term of coronary events was almost balanced by the increase in major bleedings. The balance between potential benefit and harm of aspirin differs in each person and appears to be favorable in subjects at higher cardio-vascular risk. Older people have increased risk of hemorrhage as well as increased risk of heart attack and stroke. As a consequence, it is important consider both likelihoods of benefits as well as harm within the lifespan and functioning of the person. The older people who most likely benefit from aspirin in primary prevention are those at higher cardio vascular risk, with preserved functional abilities, low comorbidity, low risk of bleeding and a prolonged life expectancy. PMID- 27374043 TI - High blood pressure and syncope: orthostatic hypotension as a link. AB - The prevalence of hypertension increases with the age. Diagnostic criteria are the same as for the young, but in older adults isolated systolic hypertension is more frequent, due to loss of vascular compliance. Blood pressure should be measured on both sides in the seated position, moreover in the supine and upright position to detect orthostatic hypotension. Ambulatory blood pressure monitoring is useful to detect white coat hypertension and masked hypertension, to tailor the treatment and search for diurnal and nocturnal blood pressure pattern abnormalities. Given that frailty can affect the relationship between blood pressure and mortality, the clinician should properly evaluate and monitor physical performance and cognitive status, throughout specific tools, as the Fried Frailty Phenotype, aiming at a systolic blood pressure target between 130 and 150 mmHg. Before starting hypotensive drugs, a careful risk and benefits' evaluation should be performed given the high risk of hypertension and hypotension consequences and the frequent coexistence of orthostatic hypotension, which predisposes to syncope and falls. PMID- 27374044 TI - High blood pressure in older subjects with cognitive impairment. AB - High blood pressure and cognitive impairment often coexist in old age, but their pathophysiological association is complex. Several longitudinal studies have shown that high blood pressure at midlife is a risk factor for cognitive impairment and dementia, although this association is much less clear in old age. The effect of blood pressure lowering in reducing the risk of dementia is only borderline significant in clinical trials of older subjects, partly due to the insufficient follow-up time. Conversely, dementia onset is associated with a decrease of blood pressure values, probably secondary to neurodegeneration. Prognostic effect of blood pressure values in cognitively impaired older subjects is still unclear, with aggressive blood pressure lowering being potentially harmful in this patients category. Brief cognitive screening, coupled with simple motor assessment, are warranted to identify frail older subjects who need a more cautious approach to antihypertensive treatment. Values obtained with ambulatory blood pressure monitoring seem more useful than clinical ones to predict the outcome of cognitively impaired older subjects. Future studies should identify the most appropriate blood pressure targets in older subjects with cognitive impairment. PMID- 27374045 TI - Cardiovascular prevention and rehabilitation in the elderly: evidence for cardiac rehabilitation after myocardial infarction or chronic heart failure. AB - Cardiac rehabilitation in the elderly today often represents a utopia. The international scientific literature takes little into account this type of prescription for old people, although they represent a large and growing proportion of cardiac patients, with acute coronary syndrome or heart failure, which we have to manage in everyday life. Furthermore, interventions of health education, clinical follow up, rehospitalisation prevention and prescription of tailored exercise, are sometimes more necessary in this kind of patients, given the presence of multimorbidity, functional dependence, frailty, sarcopenia, social neglect. Most of the data on the feasibility, safety and efficacy of cardiac rehabilitation are favourable, but they are few and apparently not strong enough to convince the medical community. Therefore is necessary to join efforts to identify the geriatric patient's peculiarities and plan a suitable program of cardiac rehabilitation, which takes into account the multi-dimensionality and complexity of typical problems of the elderly, for which the classical cardiac outcomes can be limited. PMID- 27374046 TI - Barriers to cardiac rehabilitation access of older heart failure patients and strategies for better implementation. AB - In heart failure (HF), cardiac rehabilitation (CR) may reduce decompensations, hospitalization, and ultimately mortality in long term. Many studies over the past decade have demonstrated that aerobic exercise training is effective and safe in stable patients with HF. Exercise CR resulted in a clinically important improvement in the QOL. Several clinical and psychosocial factors are associated with decreased participation in CR programs of elderly HF patients, such as perception of exercise as tiring or painful, comorbidities, lack of physician encouragement, and opinion that CR will not improve their health status. Besides low functional capacity, and chronic deconditioning may also deter patients from participating in CR programs. Recent data suggest that current smoking, a BMI >=30 kg/m2, diabetes mellitus, and cognitive dysfunction are associated with failure to enroll in outpatient CR in older age group. Moreover the lack of availability of CR facilities or the absence of financial refunds for enrolment of CHF patients in cardiac rehabilitation programs can play a crucial role. Many of this factors are modifiable through patient education and self care strategy instruction, health providers sensibilization, and implementing economic measures in order to make CR affordable. PMID- 27374047 TI - Are clinical trial results transferable in the real life? AB - Generally in the clinical practice patients are more complex in comparison with those included in the clinical trials. In this article, we discuss three relevant items, which may implement the transferability of the clinical trial results in the real world. The observational studies have fewer restrictions on the number of patients included, due to more relaxed inclusion and exlusion criteria than in randomized clinical trials. The absence of randomization however may lead to potential for bias. The recurrent event analysis may extend the positive results of clinical trials regarding the reductions of the first primary endpoint event to total events, including those beyond the first event. This analysis is of great interest in the clinical practice, where recurrent events are common. Finally the reliability of subgroup analysis is discussed. Pre-specified subgroup analyses are more credible and valuable than post-hoc analyses. PMID- 27374048 TI - Cardiac rehabilitation is safe and effective also in the elderly, but don't forget about drugs! AB - In the setting of heart failure (HF) pharmacotherapy demonstrates a quantifiable improvement in exercise tolerance also in HF with preserved ejection fraction (HFpEF). For patients with HFpEF, often older, with higher prevalence of hypertension, diabetes mellitus, atrial fibrillation and other comorbidities, endpoints such as quality of life and functional capacity may be more clinically relevant. However several study show as the use of ACE-I and B-blocker were lesser than expected. Beta-blocker therapy is the keystone of pharmacotherapy of HF patients and exercise training is the essential core of rehabilitation programs, it is important to elucidate the relationship between these therapies. Exercise training improves the clinical status of HF, improving left ventricular ejection fraction and improving quality of life, but it is possible that b blocker may attenuate exercise training adaptations. Despite this, possible adverse b-blocker effects are just presumed and not confirmed by published randomized clinical trials. Metanalysis suggests that b-blocker compared with placebo enhances improvements in cardiorespiratory performance in exercise training intervention. Despite these evidences, prescription of gold standard therapy and adherence are still suboptimal and should be a priority goal for all CR program. PMID- 27374049 TI - Resistance training and sarcopenia. AB - Aging is inexorably accompanied by a progressive decline of muscle mass, quality and strength. The resulting condition has been termed sarcopenia. Age-related sarcopenia can be accelerated by a variety of factors including changes in the hormonal milieu, inactivity, poor nutrition, chronic illness, and loss of integrity and function in the peripheral and central nervous systems. The downstream mechanisms by which these risk factors cause sarcopenia are not completely understood. Exercise training (particularly resistance training) has long been identified as the most promising method for increasing muscle mass and strength among older people. New interventions aimed at preventing muscle atrophy, promoting muscle growth and ultimately, maintaining muscle functions during aging are discussed. Understanding how age affects muscle-related gene expression, protein recycling and resynthesis, post-translational modification and turnover will be crucial to identify new treatment options. PMID- 27374050 TI - Cardiopulmonary rehabilitation in patiens with heart failure and chronic pulmonary disease. AB - The epidemiology of chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are well known. Each of these conditions has an important impact on quality of life and functional status and on healthcare consumption. Through shared risk factors and pathophysiological mechanisms CHF and COPD coexist more frequently than expected from the respective populations observed by the pulmonologist or cardiologist. This has important prognostic and therapeutic implications. Several registry-based studies and post-hoc analyses of large randomized controlled trials evaluating COPD as a comorbidity in CHF outpatients have highlighted the negative prognostic impact of the comorbidity in terms of constraint in use of recommended treatments. Among them, the cardiopulmonary rehabilitation may play a significant role. Even in these patients, in fact, a rehabilitative approach focused on physical training programs can positively impact functional autonomy, exercise tolerance and quality of life. PMID- 27374051 TI - Cholesterol: until which age 'the lower the better'? AB - In the elderly and particularly in the very elderly the prognostic role of hypercholesterolemia is uncertain and there are conflicting data from the literature. In some studies, the relation between high levels of cholesterol and cardiovascular events, strongly demonstrated for younger subjects, has been confirmed also in the elderly, conversely in other studies a relation between low cholesterol levels and higher mortality risk has been described, particularly in the very elderly. Furthermore, uncertainties regarding hypercholesterolemia treatment have been raised both in secondary and particularly in the primary prevention setting, because elderly subjects and particularly the very elderly have been excluded from randomized clinical trials. In this article the prognostic role of hypercholerlemia and its reduction in the elderly patients both in primary and secondary prevention settings are assessed. PMID- 27374052 TI - Fluorescence enhancement in visible light: dielectric or noble metal? AB - A high permittivity dielectric gives the impression of outperforming plasmonic noble metal in visible light fluorescence enhancement primarily because of its small loss. Nonetheless, the performances of these two platforms in various situations remain obscure due to the different optical confinement mechanisms as well as the complexity in the fluorescence enhancement process. This study presents a comprehensive comparison between these two platforms based on nanoparticles (NPs) to evaluate their capability and applicability in fluorescence enhancement by taking into account the fluorescence excitation rate, the quantum yield, the fluorophore wavelengths and Stokes shifts as well as the far field intensity. In a low permittivity sensing medium (e.g. air), the dielectric NP can achieve comparable or higher fluorescence enhancement than the metal NP due to its decent NP-enhanced excitation rate and larger quantum yield. In a relatively high permittivity sensing medium (e.g. water), however, there is a significant decrement of the excitation rate of the dielectric NP as the permittivity contrast decreases, leading to a smaller fluorescence enhancement compared to the metallic counterpart. Combining the fluorescence enhancement and the far field intensity studies, we further conclude that for both dielectric and plasmonic NPs, the optimal situation occurs when the fluorescence excitation wavelength, the fluorescence emission wavelength and the electric-dipole-mode of the dielectric NP (or the plasmonic resonance of the metal NP) are the same and all fall in the low conductivity region of the NP material. We also find that the electric-dipole-mode of the dielectric NP performs better than the magnetic dipole-mode for fluorescence enhancement applications because only the electric dipole-mode can be strongly excited by the routinely used fluorescent dyes and quantum dots, which behave as electric dipoles by nature. PMID- 27374053 TI - Resolving Non-Specific and Specific Adhesive Interactions of Catechols at Solid/Liquid Interfaces at the Molecular Scale. AB - The adhesive system of mussels evolved into a powerful and adaptive system with affinity to a wide range of surfaces. It is widely known that thereby 3,4 dihydroxyphenylalanine (Dopa) plays a central role. However underlying binding energies remain unknown at the single molecular scale. Here, we use single molecule force spectroscopy to estimate binding energies of single catechols with a large range of opposing chemical functionalities. Our data demonstrate significant interactions of Dopa with all functionalities, yet most interactions fall within the medium-strong range of 10-20 kB T. Only bidentate binding to TiO2 surfaces exhibits a higher binding energy of 29 kB T. Our data also demonstrate at the single-molecule level that oxidized Dopa and amines exhibit interaction energies in the range of covalent bonds, confirming the important role of Dopa for cross-linking in the bulk mussel adhesive. We anticipate that our approach and data will further advance the understanding of biologic and technologic adhesives. PMID- 27374054 TI - Solid state NMR studies of gels derived from low molecular mass gelators. AB - Since its invention more than six decades ago, nuclear magnetic resonance (NMR) spectroscopy has evolved as an inevitable part of chemical as well as structural analysis of small molecules, polymers, biomaterials and hybrid materials. In the solution state, due to the increased viscosity of complex viscoelastic fluids such as gels, liquid crystals and other soft materials, the rate of molecular tumbling is reduced, which in turn affects the chemical shift anisotropy, dipolar and quadrupolar interactions. As a consequence the solution state NMR spectra show broad lines, and therefore, extracting detailed structural information is a challenging task. In this context, solid state (SS) NMR has the ability to distinguish between a minute amount of polymorphic forms, conformational changes, and the number of non-equivalent molecules in an asymmetric unit of a crystal lattice, and to provide both qualitative as well as quantitative analytical data with a short-range order. Therefore, SS NMR has continued to evolve as an indispensable tool for structural analysis and gave birth to a new field called NMR crystallography. Solid state cross polarization (CP) and high resolution (HR) magic angle spinning (MAS) NMR spectroscopy has been used to study weak interactions in polymer gels. However, the application of SS NMR spectroscopy to study gels derived from low molecular weight gelators has been limited until recently. In this review, we will focus on the importance of solid state NMR spectroscopy in understanding and elucidating the structure of supramolecular gels derived from low molecular weight gelators with selected examples. PMID- 27374055 TI - Accuracy of fetal age estimates using transrectal ultrasonography for predicting calving dates in dairy cows in seasonally calving herds in New Zealand. AB - AIM: To describe the accuracy of transrectal ultrasonography for predicting calving dates in dairy cows under typical New Zealand conditions and to assess potential risk factors for differences between predicted and actual calving dates. METHODS: Data were collected from 116 seasonally calving herds over 2 years in a retrospective single cohort study. Transrectal ultrasonography was undertaken by experienced veterinarians (n=12) to determine if cows were pregnant, and if so to estimate fetal age. Predicted calving date was calculated by adding 282 days to the estimated conception date. Accuracy was assessed using differences between predicted and actual calving dates for each animal. Potential risk factors for animals calving >10 days before or after their predicted calving date were assessed using multinomial logistic regression models. RESULTS: The study population comprised 83,104 cows over the 2 years of the study; 75,037 (90.3%) cows calved within 10 days of their predicted calving date, 3,683 (4.4%) calved >10 days earlier, and 4,384 (5.3%) >10 days later, than predicted. Risk factors for calving >10 days before or after the predicted calving date included having >1 artificial insemination (AI) before pregnancy diagnosis (p=0.03), where the cow's most recent AI was <21 days before the end of the herd's AI period (p<0.01), and where the diagnosis was made at the second or third herd-visit (p<0.01). The probability of calving being >10 days later than predicted also increased when the fetus was >=13 weeks old at pregnancy diagnosis (p<0.01). CONCLUSIONS AND CLINICAL RELEVANCE: In this study, >90% of cows diagnosed pregnant by veterinarians using transrectal ultrasonography calved within 10 days of the predicted calving date. In herds where herd reproductive performance is high, it would be expected that more cows would conceive to their first AI, and potentially fewer cows would have AI close to the end of the herd's AI period, which would increase diagnostic accuracy. Where herd managers rely on accurate predicted calving dates they should be informed about realistic expected accuracy. For greatest accuracy, a complete AI history should be made available to the person performing the pregnancy diagnoses and cows at most risk of having inaccurate predicted calving dates should be identified. PMID- 27374057 TI - Transcription of dbp from the coding region of the Bm17 gene is required for the efficient propagation of Bombyx mori nucleopolyhedrovirus. AB - A Bombyx mori nucleopolyhedrovirus (BmNPV) mutant was generated, in which Bm17 was disrupted by the insertion of a lacZ reporter cassette. This mutant (Bm17D) exhibited defective phenotypes, i.e., budded viruses (BVs) and occlusion bodies (OBs) were less produced in both B. mori cultured cells and larvae. However, a repair virus (Bm17DR), lacking endogenous Bm17 but expressing Bm17 with its endogenous promoter at a different genomic locus, did not rescue most of the defective phenotypes of Bm17D. Transcriptional units in the Bm17 region were surveyed in detail using a transcriptome map of BmNPV-infected cells. It was found that one of the transcriptional start sites (TSSs) of dbp (Bm16) is located within the Bm17 coding region and that it does not likely function in the genome of Bm17D- or Bm17DR by inserting a lacZ cassette. From the obtained results, it was shown that both dbp transcription and DBP protein expression were markedly reduced in Bm17D- or Bm17DR-infected cells. This indicates that reduced dbp transcription alone results in decreased BV and OB production during BmNPV infection. PMID- 27374056 TI - A Comparison Study of Fixed and Mixed Effect Models for Gene Level Association Studies of Complex Traits. AB - In association studies of complex traits, fixed-effect regression models are usually used to test for association between traits and major gene loci. In recent years, variance-component tests based on mixed models were developed for region-based genetic variant association tests. In the mixed models, the association is tested by a null hypothesis of zero variance via a sequence kernel association test (SKAT), its optimal unified test (SKAT-O), and a combined sum test of rare and common variant effect (SKAT-C). Although there are some comparison studies to evaluate the performance of mixed and fixed models, there is no systematic analysis to determine when the mixed models perform better and when the fixed models perform better. Here we evaluated, based on extensive simulations, the performance of the fixed and mixed model statistics, using genetic variants located in 3, 6, 9, 12, and 15 kb simulated regions. We compared the performance of three models: (i) mixed models that lead to SKAT, SKAT-O, and SKAT-C, (ii) traditional fixed-effect additive models, and (iii) fixed-effect functional regression models. To evaluate the type I error rates of the tests of fixed models, we generated genotype data by two methods: (i) using all variants, (ii) using only rare variants. We found that the fixed-effect tests accurately control or have low false positive rates. We performed simulation analyses to compare power for two scenarios: (i) all causal variants are rare, (ii) some causal variants are rare and some are common. Either one or both of the fixed effect models performed better than or similar to the mixed models except when (1) the region sizes are 12 and 15 kb and (2) effect sizes are small. Therefore, the assumption of mixed models could be satisfied and SKAT/SKAT-O/SKAT-C could perform better if the number of causal variants is large and each causal variant contributes a small amount to the traits (i.e., polygenes). In major gene association studies, we argue that the fixed-effect models perform better or similarly to mixed models in most cases because some variants should affect the traits relatively large. In practice, it makes sense to perform analysis by both the fixed and mixed effect models and to make a comparison, and this can be readily done using our R codes and the SKAT packages. PMID- 27374058 TI - Pathogenicity and horizontal transmission studies of caprine parainfluenza virus type 3 JS2013 strain in goats. AB - Parainfluenza virus type 3 (PIV3) is one of the most important viral respiratory pathogens for humans and for many animals, but goat infection has been rarely reported. In 2014, one novel PIV3 strain was first isolated from goats suffered respiratory diseases in Jiangsu and Anhui provinces of eastern China and named as caprine PIV3 (CPIV3) JS2013. In order to systematically evaluate the pathogenicity and horizontal transmission ability of this new virus, experimental infection of goats with the CPIV3 strain was done. The virus-inoculated goats (challenge control (CC) group) displayed coughing and nasal discharges from 3days post infection (dpi) and lasted for about 2 weeks. Two goats in group CC showed fever between 7 and 12dpi. As detected by a TaqMan real time quantitative RT-PCR (qRT-PCR), viremia was detected during 3-11dpi, peaked at 6dpi; and virus shedding from nasal discharge and faeces were confirmed during 3-21dpi and 4 21dpi, respectively. Virus-specific HI antibodies and neutralizing antibodies (NAs) became positive since 7dpi and 14dpi; peaked at 14dpi and 28dpi, respectively; and lasted at least 70days. Pathological lesions were mainly found on the lungs and tracheas. In addition, viruses were also detected in part of the tracheal secretion and lung samples, and the viral load in tracheal secretion was higher than that in lungs. Goats in horizontal infected group (hCC, kept in different cages in the same house with CC group) showed to be horizontally infected, with slightly milder clinical signs and pathological changes; and slightly shorter period of viremia and virus shedding. This was the first report of the detailed pathogenicity characterization of the novel CPIV3 and demonstrated its horizontal transmission ability. The results would be helpful for further studies on the preventive and control strategies for CPIV3 infections. PMID- 27374059 TI - Roles of long noncoding RNAs in hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with high prevalence and lethality. Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection are the major risk factors for HCC. Long noncoding RNAs (lncRNAs) are involved in diverse biological processes, and aberrant lncRNA expression is relevant to many human diseases including HCC. Although many researches on HCC have been reported and lncRNAs roles in carcinogenesis have been highlighted recently, reports on roles of lncRNAs in HBV/HCV-induced HCC are limited. In this review, we concentrate on recent progress regarding the functional roles of lncRNAs in HCC and HBV/HCV-related HCC. PMID- 27374060 TI - Bovine herpesvirus-1: Genetic diversity of field strains from cattle with respiratory disease, genital, fetal disease and systemic neonatal disease and their relationship to vaccine strains. AB - Bovine herpesvirus-1 (BoHV-1) causes disease in cattle with varied clinical forms. In the U.S. there are two BoHV1 subtypes, BoHV-1.1 and BoHV-1.2b. Control programs in North America incorporate modified live (MLV) or killed (KV) viral vaccines. However, BoHV-1 strains continue to be isolated from diseased animals or fetuses after vaccination. It is possible to differentiate BoHV-1 wild-type from MLV vaccine strains by determining their single nucleotide polymorphism (SNP) patterns through either whole-genome sequencing or PCR sequencing of genomic regions containing vaccine-defining SNPs. To determine the BoHV-1 subtype in clinical isolates and their relationship to MLV strains, 8 isolates from varied clinical disease at three different laboratories in the U.S. were sequenced and phylogenetically analyzed. Five samples were isolated within the past 5 years from New York and 3 were archived samples recovered 35 years prior from Oklahoma and Louisiana. Based on phylogenetic analysis, four of the cases appeared to be due to an MLV vaccine: 3 cases of aborted fetuses and one neonate with systemic BoHV-1 disease. One aborted fetus was from a herd with no reported history of MLV vaccination in two years. The remaining four isolates did not group with any MLV vaccines: two were associated with bovine respiratory disease, one with vulvovaginitis, and a fourth was determined to be a BoHV-1.2b respiratory isolate. Recovery of BoHV-1.1 that is very closely related to an MLV vaccine virus from a herd not receiving vaccines in an extended period prior to its isolation suggests that MLV viruses may remain latent or circulate within herds for long periods. PMID- 27374061 TI - Anti-influenza virus activity of high-mannose binding lectins derived from genus Pseudomonas. AB - Lectin PFL binding high-mannose glycan derived from Pseudomonas fluorescens and other homologous lectins: PML derived from Pseudomonas mandelii and PTL derived from Pseudomonas taiwanensis were examined for antiviral activity. The cDNA of these lectin genes were synthesized, cloned, expressed in Escherichia coli. The expressed lectins were purified by gel filtrations, and supplied to cultures infected with several strains of influenza virus. These three lectins have inhibited propagation of influenza viruses with a similar extent, 50% of inhibition-dose was around ten nanomolar concentration. An immunofluorescent microscopy, a microarray analysis, and several infection experiments with different time periods of lectin addition or using the competitor substrates indicated that binding of these lectins with high-mannose glycan on HA protein of influenza virus could block the virus entry into the host cells, thereby resulting in inhibition of the virus propagation. These Pseudomonas-derived lectins would be protential and attractive antiviral agents targeting glycoproteins of enveloped viruses including influenza virus. PMID- 27374062 TI - Structure of 'linkerless' hydroxamic acid inhibitor-HDAC8 complex confirms the formation of an isoform-specific subpocket. AB - Histone deacetylases (HDACs) catalyze the hydrolysis of acetylated lysine side chains in histone and non-histone proteins, and play a critical role in the regulation of many biological processes, including cell differentiation, proliferation, senescence, and apoptosis. Aberrant HDAC activity is associated with cancer, making these enzymes important targets for drug design. In general, HDAC inhibitors (HDACi) block the proliferation of tumor cells by inducing cell differentiation, cell cycle arrest, and/or apoptosis, and comprise some of the leading therapies in cancer treatments. To date, four HDACi have been FDA approved for the treatment of cancers: suberoylanilide hydroxamic acid (SAHA, Vorinostat, Zolinza(r)), romidepsin (FK228, Istodax(r)), belinostat (Beleodaq(r)), and panobinostat (Farydak(r)). Most current inhibitors are pan HDACi, and non-selectively target a number of HDAC isoforms. Six previously reported HDACi were rationally designed, however, to target a unique sub-pocket found only in HDAC8. While these inhibitors were indeed potent against HDAC8, and even demonstrated specificity for HDAC8 over HDACs 1 and 6, there were no structural data to confirm the mode of binding. Here we report the X-ray crystal structure of Compound 6 complexed with HDAC8 to 1.98A resolution. We also describe the use of molecular docking studies to explore the binding interactions of the other 5 related HDACi. Our studies confirm that the HDACi induce the formation of and bind in the HDAC8-specific subpocket, offering insights into isoform-specific inhibition. PMID- 27374063 TI - Arterial duplex for diagnosis of peripheral arterial emboli. AB - BACKGROUND: Whether duplex ultrasound (DUS) imaging alone can be used to successfully plan revascularization for peripheral arterial embolism (PAE) is unknown. This study evaluated the utility of DUS imaging alone for the diagnosis and treatment of PAE. METHODS: Patients with cardiogenic PAE to the lower or upper extremities during a 20-year period were retrospectively evaluated. Patients with visceral or cerebral PAE were excluded. Diagnosis by DUS imaging alone was compared with contrast angiography (CA) or computed tomography angiography (CTA). Patient demographics, use of intraoperative CA, need for reintervention, length of revascularization procedure, and rate of fasciotomy and amputation were compared. Mean peak systolic velocity (PSV; cm/s) measured at the proximal, middle, and distal segment of each artery from the common femoral to the distal tibial arteries was also compared with surgical outcomes. RESULTS: We identified 203 extremities in 182 patients with PAE. Preoperative imaging was obtained in 89%, including DUS imaging alone (44%), CA (37%), and CTA (7%). DUS imaging was used more frequently than CA or CTA in women, older patients, patients with congestive heart failure, upper extremity PAE, and patients on antiplatelet agents preoperatively. Use of intraoperative CA, need for reintervention, rate of fasciotomy and limb loss, and hospital length of stay were similar between the two groups. No upper extremities required amputation. Patients with lower extremity emboli who underwent fasciotomy had lower mean PSVs than those free from fasciotomy at the popliteal (4 +/- 6 cm/s vs 31 +/- 62 cm/s; P = .03), anterior tibial (1 +/- 3 cm/s vs 10 +/- 16 cm/s; P = .004), and posterior tibial (2 +/- 3 cm/s vs 9 +/- 15 cm/s; P = .03) arteries. The 30-day mortality for the series was 25% with a median follow-up of 7.4 months. The only predictor of 30-day mortality on multivariate analysis was tobacco use (odds ratio, 3.1; 95% confidence interval, 1.4-7.0). CONCLUSIONS: Surgical outcomes and survival for patients evaluated by preoperative DUS imaging alone for PAE are equivalent to patients evaluated with CA or CTA. PSVs in the tibiopopliteal arteries may predict the need for fasciotomy. Preoperative DUS imaging alone is sufficient for operative planning in patients with symptoms suggestive of PAE. PMID- 27374064 TI - Vascular Quality Initiative and National Surgical Quality Improvement Program registries capture different populations and outcomes in open infrainguinal bypass. AB - OBJECTIVE: Both the Vascular Quality Initiative (VQI) and the National Surgical Quality Improvement Program Procedure Targeted (NSQIP-PT) databases aim to track outcomes and to improve quality in vascular surgery. However, both registries are subject to significant selection bias. The objective of this study was to compare the populations and outcomes of a single procedure in VQI and NSQIP-PT and to identify areas of similarity and discrepancy. METHODS: Deidentified regional data were provided by VQI, and the public use files were provided by NSQIP. Patient characteristics and outcomes were compared between data sets with parametric and nonparametric statistical tests as appropriate. For variables with different definitions between VQI and NSQIP-PT, a standardized definition was created to permit comparison across databases. To account for differences in populations of patients between the data sets, VQI and NSQIP-PT records were propensity matched, allowing a comparison of outcomes between databases adjusted for case mix. RESULTS: VQI contained 1358 records from 2011 to 2015, whereas NSQIP-PT contained 5273 complete records from 2011 to 2013. Patients in VQI are younger than those in NSQIP (65 [15] vs 68 [16] years; P < .001) and were less likely to have congestive heart failure (1.7% vs 3.1%; P = .005), to be on dialysis (4.0% vs 6.1%; P = .003), or to be receiving preoperative aspirin (62% vs 79%; P < .001) or statin therapy (63% vs 68%; P < .001). Significant discrepancies were noted in preoperative angina symptoms, prior myocardial infarction, and prior percutaneous coronary intervention, with 0, 1, and 0 NSQIP patients, respectively, having these risk factors compared with 9.4%, 0.7%, and 19.5% of the VQI cohort. Approximately 20% of patients in VQI underwent surgery for acute limb ischemia, which is not a recognized indication in NSQIP-PT. Overall 30-day mortality was equivalent (2.0% vs 1.8%; P = .6), as was composite myocardial infarction/stroke (3.9% vs 3.2%; P = .2). Major amputation (3.3% vs 1.6%; P = .002), return to operating room (16.1% vs 11.5%; P < .001), and wound infection rates (12.8% vs 1.4%; P < .001) were higher in NSQIP relative to VQI. Bleeding rates were higher in VQI (36.5% vs 17.2%; P < .001). Significant differences persisted in the propensity-matched groups. CONCLUSIONS: This is the first study to compare patient characteristics and outcome reported in the VQI and NSQIP-PT registries. These data documented statistically significant differences in demographics and comorbidities as well as in outcomes between databases. Physicians, payers, and the public should consider differences between these databases when reporting on outcomes and quality. Results from these two registries should not be directly compared. PMID- 27374066 TI - Discussion. PMID- 27374067 TI - Socioeconomic disparities affect survival after aortic dissection. AB - OBJECTIVE: The effect of socioeconomic status (SES) on the course of many disease states has been documented in the literature but has not been studied in aortic dissection. This study evaluated the effect of SES on 30-day and long-term survival of patients after aortic dissection. METHODS: Hospital discharge records were used to identify patients with acute aortic dissection. Patient demographics, insurance status, comorbidities, and 30-day mortality were collected. Home addresses were used to estimate each patient's median household income, and the neighborhood deprivation index, a measure of SES, was determined. Long-term survival was assessed by review of the Social Security Death Index. Associations between demographics, insurance status, comorbidities, and poverty level were investigated to determine their effect on survival. RESULTS: There were 212 aortic dissections; of which, 118 were type A and 94 were type B. Median follow-up was 7.6 years. The neighborhood deprivation index (hazard ratio, 1.43; 95% confidence interval, 1.16-1.78; P = .001) was associated with reduced long term survival and was also significantly associated with 30-day mortality (hazard ratio, 1.43; 95% confidence interval, 1.05-1.93; P = .02). The mean neighborhood deprivation index score was higher in patients with type B aortic dissections (0.45 +/- 0.93) than in those with type A aortic dissections (0.16 +/- 0.96; P = .029). CONCLUSIONS: Patients with a lower SES had reduced short-term and long term survival after aortic dissection. Patients with type B dissection live in lower socioeconomic neighborhoods than patients with type A dissection. PMID- 27374065 TI - Dorsomorphin homologue 1, a highly selective small-molecule bone morphogenetic protein inhibitor, suppresses medial artery calcification. AB - BACKGROUND: Medial artery calcification develops in diabetes, chronic kidney disease, and as part of the aging process. It is associated with increased morbidity and mortality in vascular patients. Bone morphogenetic proteins (BMPs) have previously been implicated in the initiation and progression of vascular calcification. We thus evaluated whether dorsomorphin homologue 1 (DMH1), a highly selective BMP inhibitor, could attenuate vascular calcification in vitro and in an organ culture model of medial calcification. METHODS: Confluent human aortic smooth muscle cells (SMCs) were cultured in calcification medium containing 3.0 mM inorganic phosphate (Pi) for 7 days with or without DMH1. Medial calcification was assessed using an aortic organ culture model. Calcification was visualized by alizarin red S staining, and calcium concentration was assessed by an o-cresolphthalein complexone calcium assay. Osteogenic cell and vascular SMC markers were determined by Western blot, quantitative reverse transcription polymerase chain reaction, and immunohistochemical staining. RESULTS: DMH1 reduced Pi-induced calcium deposition in human SMCs. It also antagonized human recombinant BMP2-induced calcium accumulation. Western blot further revealed that DMH1 was able to block Pi mediated upregulation of the osteoblast markers osterix and alkaline phosphatase and downregulation of the SMC markers smooth muscle myosin heavy chain and SM22alpha as well as p-Smad1/5/8, suggesting that DMH1 may regulate SMC osteogenic differentiation through the BMP/Smad1/5/8 signaling pathway. Finally, using an ex vivo aortic ring organ culture model, we observed that DMH1 reduces Pi-induced aortic medial calcification. CONCLUSIONS: The selective BMP inhibitor DMH1 can inhibit calcium accumulation in vascular SMCs and arterial segments exposed to elevated phosphate levels. Such small molecules may have clinical utility in reducing medial artery calcification in our population of vascular patients. PMID- 27374068 TI - Aortic outflow occlusion predicts rupture of abdominal aortic aneurysm. AB - BACKGROUND: Current threshold recommendations for elective abdominal aortic aneurysm (AAA) repair are based solely on maximal AAA diameter. Peak wall stress (PWS) has been demonstrated to be a better predictor than AAA diameter of AAA rupture risk. However, PWS calculations are time-intensive, not widely available, and therefore not yet clinically practical. In addition, PWS analysis does not account for variations in wall strength between patients. We therefore sought to identify surrogate clinical markers of increased PWS and decreased aortic wall strength to better predict AAA rupture risk. METHODS: Patients treated at our institution from 2001 to 2014 for ruptured AAA (rAAA) were retrospectively identified and grouped into patients with small rAAA (maximum diameter <6 cm) or large rAAA (>6 cm). Patients with large (>6 cm) non-rAAA were also identified sequentially from 2009 for comparison. Demographics, vascular risk factors, maximal aortic diameter, and aortic outflow occlusion (AOO) were recorded. AOO was defined as complete occlusion of the common, internal, or external iliac artery. Computational fluid dynamics and finite element analysis simulations were performed to calculate wall stress distributions and to extract PWS. RESULTS: We identified 61 patients with rAAA, of which 15 ruptured with AAA diameter <60 mm (small rAAA group). Patients with small rAAAs were more likely to have peripheral arterial disease (PAD) and chronic obstructive pulmonary disease (COPD) than were patients in the large non-rAAA group. Patients with small rAAAs were also more likely to have AOO compared with non-rAAAs >60 mm (27% vs 8%; P = .047). Among all patients with rAAAs, those with AOO ruptured at smaller mean AAA diameters than in patients without AOO (62.1 +/- 11.8 mm vs 72.5 +/- 16.4 mm; P = .024). PWS calculations of a representative small rAAA and a large non-rAAA showed a substantial increase in PWS with AOO. CONCLUSIONS: We demonstrate that AOO, PAD, and COPD in AAA are associated with rAAAs at smaller diameters. AOO appears to increase PWS, whereas COPD and PAD may be surrogate markers of decreased aortic wall strength. We therefore recommend consideration of early, elective AAA repair in patients with AOO, PAD, or COPD to minimize risk of early rupture. PMID- 27374069 TI - Oncovascular compartmental resection for retroperitoneal soft tissue sarcoma with vascular involvement. AB - OBJECTIVE: This study analyzed the outcomes of a series of consecutive patients diagnosed with a retroperitoneal soft tissue sarcoma (RSTS) with vascular involvement and who underwent a multidisciplinary operation. METHODS: Between 2000 and 2013, 126 patients were referred for oncovascular surgery in our institution. Among these, 31 consecutive patients underwent operations for RSTS with vascular involvement. A vascular/oncologic team determined the surgical strategy preoperatively. RESULTS: Median follow-up was 34.4 months (interquartile range, 48.1 months). Twenty patients (65%) were referred for primary RSTS and 11 (35%) for local recurrence. The most common histologic diagnosis was liposarcoma (54.8%), mainly high-grade and intermediate-grade RSTS. Prosthetic grafts were usually used for vascular reconstruction. Median hospital stay was 17 days (interquartile range, 14.5; range, 7-190 days). The grade 3 and 4 morbidity rate was 19.3%. Each resection was macroscopically complete (R0-R1). Median progression-free survival was 10 months, and median overall survival was not reached. Overall survival rates were 77.4% at 1 year and 61.3% at 3 years. CONCLUSIONS: Vascular resection and reconstruction are safe and feasible in case of RSTS. The morbidity rate was acceptable, and there were no perioperative deaths. Despite recurrence rates that remain high, oncovascular resection enhances resection margins and allows encouraging survival results for patients often considered as nonresectable. PMID- 27374070 TI - The long-term effects of wall attached microalgal biofilm on algae-based wastewater treatment. AB - The influence of the reactor wall attached biofilm on the nutrient removal performance was investigated in an open photobioreactor during long-term operation. Total nitrogen and phosphorus removal efficiencies were statistically similar between reactor with (reactor A) and without (reactor B) biofilm at the Hydraulic Retention Time (HRT) of 18, 13.5 and 9days. When the HRT reduced to 8days, total nitrogen and phosphorus removal efficiencies in the reactor A were 42.95+/-5.11% and 97.97+/-1.12%, respectively, while significant lower removal efficiencies (38.06+/-5.80% for total nitrogen and 83.14+/-8.16% for phosphorus) were obtained in the reactor B. The VSS concentrations throughout the test were statistically similar for the two reactors, with a mean value of 0.63+/-0.25g/l for reactor A and 0.69+/-0.20g/l for reactor B. This study indicated that the reactor wall attached biofilm supported high phosphorus and nitrogen removal, which may provide insight into the practical implementation of microalgae-based wastewater treatment. PMID- 27374072 TI - Why it is probably too soon to assess the public health effects of legalisation of recreational cannabis use in the USA. AB - The citizens of four US states-Alaska, Colorado, Oregon, and Washington-have voted to legalise the sale of cannabis to adults for recreational purposes, and more states look likely to follow. Experience with alcohol and tobacco suggests that a for-profit legal cannabis industry will increase use by making cannabis more socially acceptable to use, making it more readily available at a cheaper price, and increasing the number of users and frequency of their use. We argue that it is too early to see the full effects of legalised cannabis policies on use and harm because several factors could delay the full commercialisation of a legal cannabis industry. These factors include restrictions on various licensed producers and sellers, and legal conflicts between Federal and State laws that might provide a brake on the speed and scale of commercialisation in states that have legalised cannabis. Any increases in cannabis use and harm could be minimised if governments introduced public health policies that limited the promotional activities of a legal cannabis industry, restricted cannabis availability to adults, and maintained cannabis prices at a substantial fraction of the black market price. So far, no states have chosen to implement these policies. PMID- 27374073 TI - Recreational cannabis legalisation: details will determine mental health effects. PMID- 27374071 TI - High-throughput dual-colour precision imaging for brain-wide connectome with cytoarchitectonic landmarks at the cellular level. AB - The precise annotation and accurate identification of neural structures are prerequisites for studying mammalian brain function. The orientation of neurons and neural circuits is usually determined by mapping brain images to coarse axial sampling planar reference atlases. However, individual differences at the cellular level likely lead to position errors and an inability to orient neural projections at single-cell resolution. Here, we present a high-throughput precision imaging method that can acquire a co-localized brain-wide data set of both fluorescent-labelled neurons and counterstained cell bodies at a voxel size of 0.32 * 0.32 * 2.0 MUm in 3 days for a single mouse brain. We acquire mouse whole-brain imaging data sets of multiple types of neurons and projections with anatomical annotation at single-neuron resolution. The results show that the simultaneous acquisition of labelled neural structures and cytoarchitecture reference in the same brain greatly facilitates precise tracing of long-range projections and accurate locating of nuclei. PMID- 27374075 TI - Genetic variants of nuclear factor erythroid-derived 2-like 2 associated with the complications in Han descents with type 2 diabetes mellitus of Northeast China. AB - The transcription factor nuclear factor erythroid 2-like 2 (NFE2L2) is essential for preventing type 2 diabetes mellitus (T2DM)-induced complications in animal models. This case and control study assessed genetic variants of NFE2L2 for associations with T2DM and its complications in Han Chinese volunteers. T2DM patients with (n = 214) or without (n = 236) complications, or healthy controls (n = 359), were genotyped for six NFE2L2 single nucleotide polymorphisms (SNPs: rs2364723, rs13001694, rs10497511, rs1806649, rs1962142 and rs6726395) with TaqMan Pre-Designed SNP Genotyping and Sequence System. Serum levels of heme oxygenase-1 (HMOX1) were determined through enzyme-linked immunosorbent assay. Informative data were obtained for 341 cases and 266 controls. Between T2DM patients and controls, the genotypic and allelic frequencies and haplotypes of the SNPs were similar. However, there was a significant difference in genotypic and allelic frequencies of rs2364723, rs10497511, rs1962142 and rs6726395 between T2DM patients with and without complications, including peripheral neuropathy, nephropathy, retinopathy, foot ulcers and microangiopathy. Furthermore, HMOX1 levels were significantly higher in T2DM patients with complications than in controls. Multiple logistic regression analysis, however, showed that only rs2364723 significantly reduced levels of serum HMOX1 in T2DM patients for the GG genotype carriers compared with participants with CG+CC genotype. The data suggest that although NFE2L2 rs2364723, rs10497511, rs1962142 and rs6726395 were not associated with T2DM risk, they were significantly associated with complications of T2DM. In addition, only for rs2364723 higher serum HMOX1 levels were found in the T2DM patients with CG+CC than those with GG genotype. PMID- 27374077 TI - Single molecule probing by fluorescence and force detection. PMID- 27374076 TI - Use of fluorescent probes for ROS to tease apart Type I and Type II photochemical pathways in photodynamic therapy. AB - Photodynamic therapy involves the excitation of a non-toxic dye by harmless visible light to produce a long-lived triplet state that can interact with molecular oxygen to produce reactive oxygen species (ROS), which can damage biomolecules and kill cells. ROS produced by electron transfer (Type 1) include superoxide, hydrogen peroxide and hydroxyl radical (HO), while singlet oxygen (1O2) is produced by energy transfer. Diverse methods exist to distinguish between these two pathways, some of which are more specific or more sensitive than others. In this review we cover the use of two fluorescence probes: singlet oxygen sensor green (SOSG) detects 1O2; and 4-hydroxyphenyl-fluorescein (HPF) that detects HO. Interesting data was collected concerning the photochemical pathways of functionalized fullerenes compared to tetrapyrroles, stable synthetic bacteriochlorins with and without central metals, phenothiazinium dyes interacting with inorganic salts such as azide. PMID- 27374078 TI - Rescuing cardiac automaticity in L-type Cav1.3 channelopathies and beyond. AB - Pacemaker activity of the sino-atrial node generates the heart rate. Disease of the sinus node and impairment of atrioventricular conduction induce an excessively low ventricular rate (bradycardia), which cannot meet the needs of the organism. Bradycardia accounts for about half of the total workload of clinical cardiologists. The 'sick sinus' syndrome (SSS) is characterized by sinus bradycardia and periods of intermittent atrial fibrillation. Several genetic or acquired risk factors or pathologies can lead to SSS. Implantation of an electronic pacemaker constitutes the only available therapy for SSS. The incidence of SSS is forecast to double over the next 50 years, with ageing of the general population thus urging the development of complementary or alternative therapeutic strategies. In recent years an increasing number of mutations affecting ion channels involved in sino-atrial automaticity have been reported to underlie inheritable SSS. L-type Cav 1.3 channels play a major role in the generation and regulation of sino-atrial pacemaker activity and atrioventricular conduction. Mutation in the CACNA1D gene encoding Cav 1.3 channels induces loss of-function in channel activity and underlies the sino-atrial node dysfunction and deafness syndrome (SANDD). Mice lacking Cav 1.3 channels (Cav 1.3-/- ) fairly recapitulate SSS and constitute a precious model to test new therapeutic approaches to handle this disease. Work in our laboratory shows that targeting G protein-gated K+ (IKACh ) channels effectively rescues SSS of Cav 1.3-/- mice. This new concept of 'compensatory' ion channel targeting shines new light on the principles underlying the pacemaker mechanism and may open the way to new therapies for SSS. PMID- 27374079 TI - Chamaejasmenin B, a novel candidate, inhibits breast tumor metastasis by rebalancing TGF-beta paradox. AB - Metastasis is the leading lethal factor severely restraining the effectiveness of clinical treatment. TGF-beta is the key regulator for metastasis and influences paradoxically on cancer progression. The known TGF-beta blockers exert little selectivity on its functions, indiscriminately causing the anti-metastatic and pro-growth effects. Under such circumstances, specifically rebalancing the oncological function of TGF-beta provides a crucial oncotarget against metastasis. In our study, we established the screening platform targeting cell motility and identified a potential flavonoid, Chamaejasmenin B (ICJ), extracted from Stellera chamaejasme L..It suppressed the migration and invasion in breast cancer cells in vitro. Moreover, by dynamical quantification of breast cancer progression in small-animal imaging system, ICJ was proved to be a potent inhibitor of metastasis with minimal toxic side effects. Mechanism study further revealed that ICJ efficiently blocked TGF-beta induced EMT, disrupted the interaction between beta3 integrin-TbetaRII complex and, consequently, resulted in the selective inhibition of FAK:Src:p38 pathway. Meanwhile, specific blockage of this pathway largely attenuated the anti-metastatic function of ICJ. Importantly, in contrast with the antagonistic effects on TGF-beta induced metastasis, ICJ obviously sensitized its cytostatic activity, suggesting that it was not a pan-blocker but a rebalancer for the functional output of TGF-beta. Collectively, by targeting TGF-beta Paradox, we experimentally provided a promising candidate for metastatic intervention. PMID- 27374080 TI - MT2-MMP induces proteolysis and leads to EMT in carcinomas. AB - Epithelial-mesenchymal transition (EMT) is critical for carcinoma invasiveness and metastasis. To investigate the role of membrane-type-2 matrix metalloproteinase (MT2-MMP) in EMT, we generated lentiviral constructs of wild type (WT) and an inactive Glu260Ala (E260A) mutant MT2-MMP and derived stably transfected HCT116 and A549 cell lines. WT-transfected cells appeared mesenchymal like, whereas cells transfected with the E260A mutant were epithelial-like, as were cells treated with an MMP inhibitor (GM6001). Expression of E-cadherin, beta catenin, and zonula occludens-1 was lower in cells transfected with WT MT2-MMP compared to vector controls, cells treated with GM6001, or cells transfected with the E260A mutant. An 80-kD N-terminal fragment of E-cadherin was immunoprecipitated in conditioned medium from WT MT2-MMP cells, but not in the medium from vector controls, cells treated with GM6001, or E260A mutant cells. When endogenous expression of MT2-MMP in A2780 human ovarian cancer cells was inhibited using GM6001 or MT2-MMP-specific siRNA, levels of the 80-kD E-cadherin fragment in conditioned medium were decreased. Chick embryo chorioallantoic membrane invasion assays demonstrated that cells transfected with WT MT2-MMP were more invasive than cells transfected with control vector, treated with GM6001, or transfected with the E260A mutant. These results suggest that MT2-MMP degrades adherens and tight junction proteins and results in EMT, making it a potential mediator of EMT in carcinomas. PMID- 27374081 TI - Targeting mTOR pathway inhibits tumor growth in different molecular subtypes of triple-negative breast cancers. AB - Triple-negative breast cancers (TNBC) are characterized by frequent alterations in the PI3K/AKT/mTOR signaling pathway. In this study, we analyzed PI3K pathway activation in 67 patient-derived xenografts (PDX) of breast cancer and investigated the anti-tumor activity of the mTOR inhibitor everolimus in 15 TNBC PDX with different expression and mutational status of PI3K pathway markers. Expression of the tumor suppressors PTEN and INPP4B was lost in 55% and 76% of TNBC PDX, respectively, while mutations in PIK3CA and AKT1 genes were rare. In 7 PDX treatment with everolimus resulted in a tumor growth inhibition higher than 50%, while 8 models were classified as low responder or resistant. Basal-like, LAR (Luminal AR), mesenchymal and HER2-enriched tumors were present in both responder and resistant groups, suggesting that tumor response to everolimus is not restricted to a specific TNBC subtype. Analysis of treated tumors showed a correlation between tumor response and post-treatment phosphorylation of AKT, increased in responder PDX, while PI3K pathway markers at baseline were not sufficient to predict everolimus response. In conclusion, targeting mTOR decreased tumor growth in 7 out of 15 TNBC PDX tested. Response to everolimus occurred in different TNBC subtypes and was associated with post-treatment increase of P-AKT. PMID- 27374082 TI - Suppression of APC/CCdh1 has subtype specific biological effects in acute myeloid leukemia. AB - The E3 ubiquitin ligase and tumor suppressor APC/CCdh1 is crucial for cell cycle progression, development and differentiation in many cell types. However, little is known about the role of Cdh1 in hematopoiesis. Here we analyzed Cdh1 expression and function in malignant hematopoiesis. We found a significant decrease of Cdh1 in primary acute myeloid leukemia (AML) blasts compared to normal CD34+ cells. Thus, according to its important role in connecting cell cycle exit and differentiation, decreased expression of Cdh1 may be a mechanism contributing to the differentiation block in leukemogenesis. Indeed, knockdown (kd) of Cdh1 in HL-60 cell line (AML with maturation, FAB M2) led to less differentiated cells and a delay in PMA-induced differentiation. Acute promyelocytic leukemia (APL, FAB M3) is an AML subtype which is highly vulnerable to differentiation therapy with all-trans retinoic acid (ATRA). Accordingly, we found that APL is resistant to a Cdh1-kd mediated differentiation block. However, further depletion of Cdh1 in APL significantly reduced viability of leukemia cells upon ATRA-induced differentiation. Thus, low Cdh1 expression may be important in AML biology by contributing to the differentiation block and response to therapy depending on differences in the microenvironment and the additional genetic background. PMID- 27374083 TI - The activation of OR51E1 causes growth suppression of human prostate cancer cells. AB - The development of prostate cancer (PCa) is regulated by the androgen-dependent activity of the androgen receptor (AR). Androgen-deprivation therapy (ADT) is therefore the gold standard treatment to suppress malignant progression of PCa. Nevertheless, due to the development of castration resistance, recurrence of disease after initial response to ADT is a major obstacle to successful treatment. As G-protein coupled receptors play a fundamental role in PCa physiology, they might represent promising alternative or combinatorial targets for advanced diseases. Here, we verified gene expression of the olfactory receptors (ORs) OR51E1 [prostate-specific G-protein coupled receptor 2 (PSGR2)] and OR51E2 (PSGR) in human PCa tissue by RNA-Seq analysis and RT-PCR and elucidated the subcellular localization of both receptor proteins in human prostate tissue. The OR51E1 agonist nonanoic acid (NA) leads to the phosphorylation of various protein kinases and growth suppression of the PCa cell line LNCaP. Furthermore, treatment with NA causes reduction of androgen-mediated AR target gene expression. Interestingly, NA induces cellular senescence, which coincides with reduced E2F1 mRNA levels. In contrast, treatment with the structurally related compound 1-nonanol or the OR2AG1 agonist amyl butyrate, neither of which activates OR51E1, did not lead to reduced cell growth or an induction of cellular senescence. However, decanoic acid, another OR51E1 agonist, also induces cellular senescence. Thus, our results suggest the involvement of OR51E1 in growth processes of PCa cells and its impact on AR-mediated signaling. These findings provide novel evidences to support the functional importance of ORs in PCa pathogenesis. PMID- 27374084 TI - The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer. AB - Current treatments for pancreatic ductal adenocarcinoma (PDA) are ineffective, making this the 4th leading cause of cancer deaths. Sunitinib is a broad-spectrum inhibitor of tyrosine kinase receptors mostly known for its anti-angiogenic effects. We tested the therapeutic effects of sunitinib in pancreatic cancer using the Ela-myc transgenic mouse model. We showed that Ela-myc pancreatic tumors express PDGFR and VEGFR in blood vessels and epithelial cells, rendering these tumors sensitive to sunitinib by more than only its anti-angiogenic activity. However, sunitinib treatment of Ela-myc mice with either early or advanced tumor progression had no impact on either survival or tumor burden. Further histopathological characterization of these tumors did not reveal differences in necrosis, cell differentiation, angiogenesis, apoptosis or proliferation. In stark contrast, in vitro sunitinib treatment of Ela-myc- derived cell lines showed high sensitivity to the drug, with increased apoptosis and reduced proliferation. Correspondingly, subcutaneous tumors generated from these cell lines completely regressed in vivo after sunitinib treatments. These data point at the pancreatic tumor microenvironment as the most likely barrier preventing sunitinib treatment efficiency in vivo. Combined treatments with drugs that disrupt tumor fibrosis may enhance sunitinib therapeutic effectiveness in pancreatic cancer treatment. PMID- 27374085 TI - Dextran-Catechin: An anticancer chemically-modified natural compound targeting copper that attenuates neuroblastoma growth. AB - Neuroblastoma is frequently diagnosed at advanced stage disease and treatment includes high dose chemotherapy and surgery. Despite the use of aggressive therapy survival rates are poor and children that survive their disease experience long term side effects from their treatment, highlighting the need for effective and less toxic therapies. Catechin is a natural polyphenol with anti cancer properties and limited side effects, however its mechanism of action is unknown. Here we report that Dextran-Catechin, a conjugated form of catechin that increases serum stability, is preferentially and markedly active against neuroblastoma cells having high levels of intracellular copper, without affecting non-malignant cells. Copper transporter 1 (CTR1) is the main transporter of copper in mammalian cells and it is upregulated in neuroblastoma. Functional studies showed that depletion of CTR1 expression reduced intracellular copper levels and led to a decrease in neuroblastoma cell sensitivity to Dextran Catechin, implicating copper in the activity of this compound. Mechanistically, Dextran-Catechin was found to react with copper, inducing oxidative stress and decreasing glutathione levels, an intracellular antioxidant and regulator of copper homeostasis. In vivo, Dextran-Catechin significantly attenuated tumour growth in human xenograft and syngeneic models of neuroblastoma. Thus, Dextran Catechin targets copper, inhibits tumour growth, and may be valuable in the treatment of aggressive neuroblastoma and other cancers dependent on copper for their growth. PMID- 27374086 TI - Exogenous pyruvate facilitates cancer cell adaptation to hypoxia by serving as an oxygen surrogate. AB - Molecular oxygen is the final electron acceptor in cellular metabolism but cancer cells often become adaptive to hypoxia, which promotes resistance to chemotherapy and radiation. The reduction of endogenous glycolytic pyruvate to lactate is known as an adaptive strategy for hypoxic cells. Whether exogenous pyruvate is required for hypoxic cell proliferation by either serving as an electron acceptor or a biosynthetic substrate remains unclear. By using both hypoxic and rho0 cells defective in electron transfer chain, we show that exogenous pyruvate is required to sustain proliferation of both cancer and non-cancer cells that cannot utilize oxygen. Particularly, we show that absence of pyruvate led to glycolysis inhibition and AMPK activation along with decreased NAD+ levels in rho0 cells; and exogenous pyruvate increases lactate yield, elevates NAD+/NADH ratio and suppresses AMPK activation. Knockdown of lactate dehydrogenase significantly inhibits the rescuing effects of exogenous pyruvate. In contrast, none of pyruvate-derived metabolites tested (including acetyl-CoA, alpha-ketoglutarate, succinate and alanine) can replace pyruvate in supporting rho0 cell proliferation. Knockdown of pyruvate carboxylase, pyruvate dehydrogenase and citrate synthase do not impair exogenous pyruvate to rescue rho0 cells. Importantly, we show that exogenous pyruvate relieves ATP insufficiency and mTOR inhibition and promotes proliferation of hypoxic cells, and that well-oxygenated cells release pyruvate, providing a potential in vivo source of pyruvate. Taken together, our data support a novel pyruvate cycle model in which oxygenated cells release pyruvate for hypoxic cells as an oxygen surrogate. The pyruvate cycle may be targeted as a new therapy of hypoxic cancers. PMID- 27374087 TI - Characterization of the CD49f+/CD44+/CD24- single-cell derived stem cell population in basal-like DCIS cells. AB - The molecular mechanisms responsible for the Ductal Carcinoma in Situ (DCIS) Invasive Ductal Carcinoma (IDC) transition have yet to be elucidated. Due to the lack of molecularly targeted therapies, basal-like DCIS has a high risk of recurrence and progression to invasive and metastatic cancers. In this study, by applying a novel single-cell clonogenic approach with the CD49f+/CD44+/CD24- surface markers, we characterized the aggressive clones that have enhanced self renewal, migratory and invasive capacities derived from a human DCIS model cell line MCF10DCIS. The aggressive clones had elevated ALDH1 activity, lower global DNA methylation and increased expression of stem cell related genes, especially concurrent activation of SOX2/OCT4. In addition, we showed that the aggressive clones have increased expression of lincRNA-RoR and miR-10b compared to non aggressive clones, which enhance their self-renewal and invasive abilities. Finally, we confirmed our in vitro results in vivo, demonstrating that aggressive clones were capable of forming tumors in nude mice, whereas non-aggressive clones were not. Our data suggest that lincRNA-RoR and miR10b could be used to distinguish aggressive clones from non-aggressive clones within the heterogeneous CD49f+/CD44+/CD24- DCIS population. Our findings also provide the foundation to develop new chemoprevention agents for DCIS-IDC transition. PMID- 27374088 TI - Preparation study of indocyanine green-rituximab: A new receptor-targeted tracer for sentinel lymph node in breast cancer. AB - An appropriate receptor-targeted tracer for sentinel lymph node biopsy (SLNB) was prepared. We combined the fluorescence tracer (Indocyanine green, ICG) with Rituximab (a chimeric human/murine monoclonal antibody targeting the CD20 antigen on the surface of lymphocyte) directly to produce a new tracer (ICG-Rituximab). When the new tracer drains to the lymph node, Rituximab will combine with CD20 receptor on the B-cell surface in the lymph node. If the statue of antibody receptor connection does not reach saturation, the number of Rituximab is less than CD20. With this appropriate injection dose, the new tracer could only stay in sentinel lymph node (SLN) and make it imaging. Positive fluorescence SLN was detected 12 minutes after injection with no other organs imaging. The imaging of SLN was stable and clear for 20-24 hours. Due to SLN stained with more ICG than the lymphatic vessel, the fluorescence situation of SLN would be brighter than the vessel. The surgeon can detect the positive fluorescence SLN easily without following the fluorescence imaging lymphatic vessel. The results of our preliminary study showed that the new tracer might be useful for improving SLN imaging and worth further clinical study. SLNB with the new tracer could be a convenient method for detecting SLN and would become a standard performance in clinical practice. PMID- 27374089 TI - Prognostic value of androgen receptor in triple negative breast cancer: A meta analysis. AB - BACKGROUND: Androgen receptor (AR) is a promising therapeutic target for breast cancer. However, its prognostic value remains controversial in triple negative breast cancer (TNBC). Here we present a meta-analysis to investigate the correlation between AR expression and TNBC prognosis. RESULTS: Thirteen relevant studies with 2826 TNBC patients were included. AR positive rate was 24.4%. AR+ patients tended to have lower tumor grade (p< 0.001), but more lymph node metastases (p < 0.01). AR positivity was associated with prolonged disease free survival (HR 0.809, 95% CI = 0.659-0.995, p < 0.05), but had no significant impact on overall survival (HR 1.270, 95% CI=0.904-1.782, p = 0.168). No difference in survival existed between subgroups using different AR or estrogen receptor cutoff values. MATERIALS AND METHODS: Literature search was performed in Pubmed, Embase and Cochrane Central Register of Controlled Trials databases to identify relevant articles on AR and TNBC prognosis. Fixed- and random-effect meta-analyses were conducted based on the heterogeneity of included studies. Heterogeneity and impacts of covariates were further evaluated by subgroup analyses and meta-regression. CONCLUSION: AR positivity is associated with lower risk of disease recurrence in TNBC. Further clinical studies are warranted to clarify its prognostic role on TNBC recurrence and survival. PMID- 27374090 TI - Pim kinase inhibition sensitizes FLT3-ITD acute myeloid leukemia cells to topoisomerase 2 inhibitors through increased DNA damage and oxidative stress. AB - Internal tandem duplication of fms-like tyrosine kinase-3 (FLT3-ITD) is frequent (30 percent) in acute myeloid leukemia (AML), and is associated with short disease-free survival following chemotherapy. The serine threonine kinase Pim-1 is a pro-survival oncogene transcriptionally upregulated by FLT3-ITD that also promotes its signaling in a positive feedback loop. Thus inhibiting Pim-1 represents an attractive approach in targeting FLT3-ITD cells. Indeed, co treatment with the pan-Pim kinase inhibitor AZD1208 or expression of a kinase dead Pim-1 mutant sensitized FLT3-ITD cell lines to apoptosis triggered by chemotherapy drugs including the topoisomerase 2 inhibitors daunorubicin, etoposide and mitoxantrone, but not the nucleoside analog cytarabine. AZD1208 sensitized primary AML cells with FLT3-ITD to topoisomerase 2 inhibitors, but did not sensitize AML cells with wild-type FLT3 or remission bone marrow cells, supporting a favorable therapeutic index. Mechanistically, the enhanced apoptosis observed with AZD1208 and topoisomerase 2 inhibitor combination treatment was associated with increased DNA double-strand breaks and increased levels of reactive oxygen species (ROS), and co-treatment with the ROS scavenger N-acetyl cysteine rescued FLT3-ITD cells from AZD1208 sensitization to topoisomerase 2 inhibitors. Our data support testing of Pim kinase inhibitors with topoisomerase 2 inhibitors, but not with cytarabine, to improve treatment outcomes in AML with FLT3-ITD. PMID- 27374091 TI - Multimodal targeting of tumor vasculature and cancer stem-like cells in sarcomas with VEGF-A inhibition, HIF-1alpha inhibition, and hypoxia-activated chemotherapy. AB - Vascular endothelial growth factor A (VEGF-A) inhibition with pazopanib is an approved therapy for sarcomas, but likely results in compensatory pathways such as upregulation of hypoxia inducible factor 1alpha (HIF-1alpha). In addition, cancer stem-like cells can preferentially reside in hypoxic regions of tumors and be resistant to standard chemotherapies. In this study, we hypothesized that the combination of VEGF-A inhibition, HIF-1alpha inhibition, and hypoxia-activated chemotherapy with evofosfamide would be an effective multimodal strategy. Multimodal therapy was examined in one genetically engineered and two xenograft mouse models of sarcoma. In all three models, multimodal therapy showed greater efficacy than any single agent therapy or bimodality therapy in blocking tumor growth. Even after cessation of therapy, tumors treated with multimodal therapy remained relatively dormant for up to 2 months. Compared to the next best bimodality therapy, multimodal therapy caused 2.8-3.3 fold more DNA damage, 1.5 2.7 fold more overall apoptosis, and 2.3-3.6 fold more endothelial cell-specific apoptosis. Multimodal therapy also decreased microvessel density and HIF-1alpha activity by 85-90% and 79-89%, respectively, compared to controls. Sarcomas treated with multimodal therapy had 95-96% depletion of CD133(+) cancer stem-like ells compared to control tumors. Sarcoma cells grown as spheroids to enrich for CD133(+) cancer stem-like cells were more sensitive than monolayer cells to multimodal therapy in terms of DNA damage and apoptosis, especially under hypoxic conditions. Thus multimodal therapy of sarcomas with VEGF-A inhibition, HIF 1alpha inhibition, and hypoxia-activated chemotherapy effectively blocks sarcoma growth through inhibition of tumor vasculature and cancer stem-like cells. PMID- 27374093 TI - NO-dependent attenuation of TPA-induced immunoinflammatory skin changes in Balb/c mice by pindolol, heptaminol or ATRA, but not by verapamil. AB - Recently a mouse skin carcinogenesis study reported that a beta-blocker carvedilol displayed antitumor-properties via antihyperplastic effects. However, the antihyperplastic mechanism is unclear as the beta-blocker is characterized with multiple pleiotropic effects including stimulation of endothelial NO release and verapamil-like calcium channel blocking activity. To investigate the nature and the origin of the antihyperplastic effects, we tested topical pretreatment with pindolol, heptaminol, ATRA or verapamil against Balb/c mouse ear skin hyperplasia that was induced by TPA. We found that pindolol, heptaminol or ATRA, but not verapamil, inhibited the TPA-induced immunoinflammatory skin changes in an NO-dependent manner, which included epidermal hyperplasia, skin edema and fibrosis. Furthermore, we also observed NO-dependent alleviation of the TPA induced NK cell depletion in the ear tissues by heptaminol pretreatment. Together our results suggest that stimulation of NO generation from constitutive synthases may be primarily responsible for the reported antihyperplastic and NK cell preserving effects of the beta-blockers, and that similar effects may be observed in other immunity normalizing compounds that also promote endothelial NO synthesis. PMID- 27374092 TI - beta-MSCs: successful fusion of MSCs with beta-cells results in a beta-cell like phenotype. AB - Bone marrow mesenchymal stromal cells (MSC) have anti-inflammatory, anti apoptotic and immunosuppressive properties and are a potent source for cell therapy. Cell fusion has been proposed for rapid generation of functional new reprogrammed cells. In this study, we aimed to establish a fusion protocol of bone marrow-derived human MSCs with the rat beta-cell line (INS-1E) as well as human isolated pancreatic islets in order to generate insulin producing beta-MSCs as a cell-based treatment for diabetes.Human eGFP+ puromycin+ MSCs were co cultured with either stably mCherry-expressing rat INS-1E cells or human dispersed islet cells and treated with phytohemagglutinin (PHA-P) and polyethylene glycol (PEG) to induce fusion. MSCs and fused cells were selected by puromycin treatment.With an improved fusion protocol, 29.8 +/- 2.9% of all MSCs were beta-MSC heterokaryons based on double positivity for mCherry and eGFP.After fusion and puromycin selection, human NKX6.1 and insulin as well as rat Neurod1, Nkx2.2, MafA, Pdx1 and Ins1 mRNA were highly elevated in fused human MSC/INS-1E cells, compared to the mixed control population. Such induction of beta-cell markers was confirmed in fused human MSC/human dispersed islet cells, which showed elevated NEUROD1, NKX2.2, MAFA, PDX1 and insulin mRNA compared to the mixed control. Fused cells had higher insulin content and improved insulin secretion compared to the mixed control and insulin positive beta-MSCs also expressed nuclear PDX1. We established a protocol for fusion of human MSCs and beta cells, which resulted in a beta cell like phenotype. This could be a novel tool for cell-based therapies of diabetes. PMID- 27374094 TI - Platelets as an indicator of vascular repair in elderly Japanese men. AB - Platelets and circulating CD34-positive cells have been reported to contribute to vascular repair (endothelial repair and developing atherosclerosis). And because hypertension is known to be a strong vascular impairment factors, it should also influence the respective numbers of these factors. To clarify the clinical importance of platelets on vascular repair, we conducted a cross-sectional study of 567 Japanese men aged 60-69 who underwent an annual health check-up between 2013 and 2015. Multiple linear regression analysis of non-hypertensive subjects adjusting for classical cardiovascular risk factors showed that although platelet count did not significantly correlate with carotid intima media thickness (beta = -0.05, p = 0.356), it did positively correlate significantly with the natural log of the number of circulating CD34-positive cells (beta = 0.26, p < 0.001). In hypertensive subjects, a significant positive correlation was seen between platelets and intima media thickness (beta = 0.19, p = 0.008), whereas no significant correlation was seen between platelet count and the natural log of the number of circulating CD34-positive cells (beta = 0.11, p = 0.119). Our results indicate that platelet count is an indicator of vascular repair activity (endothelial repair and developing atherosclerosis). Additionally, hypertension might mask the beneficial effects of circulating CD34-positive cells. PMID- 27374095 TI - Integrated in vivo genetic and pharmacologic screening identifies co-inhibition of EGRF and ROCK as a potential treatment regimen for triple-negative breast cancer. AB - Breast cancer is the second most common cause of cancer-related deaths worldwide among women. Despite several therapeutic options, 15% of breast cancer patients succumb to the disease owing to tumor relapse and acquired therapy resistance. Particularly in triple-negative breast cancer (TNBC), developing effective treatments remains challenging owing to the lack of a common vulnerability that can be exploited by targeted approaches. We have previously shown that tumor cells have different requirements for growth in vivo than in vitro. Therefore, to discover novel drug targets for TNBC, we performed parallel in vivo and in vitro genetic shRNA dropout screens. We identified several potential drug targets that were required for tumor growth in vivo to a greater extent than in vitro. By combining pharmacologic inhibitors acting on a subset of these candidates, we identified a synergistic interaction between EGFR and ROCK inhibitors. This combination effectively reduced TNBC cell growth by inducing cell cycle arrest. These results illustrate the power of in vivo genetic screens and warrant further validation of EGFR and ROCK as combined pharmacologic targets for breast cancer. PMID- 27374096 TI - Carbon ion irradiation withstands cancer stem cells' migration/invasion process in Head and Neck Squamous Cell Carcinoma (HNSCC). AB - Cancer Stem Cells (CSCs) in Head and Neck Squamous Cell Carcinoma (HNSCC) have extremely aggressive profile (high migratory and invasive potential). These characteristics can explain their resistance to conventional treatment. Efficacy of photon and carbon ion irradiation with addition of cetuximab (5 nM) is studied on clonogenic death, migration and invasion of two HNSCC populations: SQ20B and SQ20B/CSCs. SQ20B express E-cadherin and overexpress EGFR while SQ20B/CSCs express N-cadherin and low EGFR. Cetuximab strongly inhibits SQ20B proliferation but has no effect on SQ20B/CSCs. 2 Gy photon irradiation enhances migration and invasiveness in both populations (p < 0.05), while cetuximab only stops SQ20B migration (p < 0.005). Carbon irradiation significantly inhibits invasion in both populations (p < 0.05), and the association with cetuximab significantly inhibits invasion in both populations (p < 0.005). These results highlight CSCs characteristics: EGFRLow, cetuximab-resistant, and highly migratory. Carbon ion irradiation appears to be a very promising therapeutic modality counteracting migration/invasion process in both parental cells and CSCs in contrast to photon irradiation. PMID- 27374097 TI - Metabolomics profiles delineate uridine deficiency contributes to mitochondria mediated apoptosis induced by celastrol in human acute promyelocytic leukemia cells. AB - Celastrol, extracted from "Thunder of God Vine", is a promising anti-cancer natural product. However, its effect on acute promyelocytic leukemia (APL) and underlying molecular mechanism are poorly understood. The purpose of this study was to explore its effect on APL and underlying mechanism based on metabolomics. Firstly, multiple assays indicated that celastrol could induce apoptosis of APL cells via p53-activated mitochondrial pathway. Secondly, unbiased metabolomics revealed that uridine was the most notable changed metabolite. Further study verified that uridine could reverse the apoptosis induced by celastrol. The decreased uridine was caused by suppressing the expression of gene encoding Dihydroorotate dehydrogenase, whose inhibitor could also induce apoptosis of APL cells. At last, mouse model confirmed that celastrol inhibited tumor growth through enhanced apoptosis. Celastrol could also decrease uridine and DHODH protein level in tumor tissues. Our in vivo study also indicated that celastrol had no systemic toxicity at pharmacological dose (2 mg/kg, i.p., 21 days). Altogether, our metabolomics study firstly reveals that uridine deficiency contributes to mitochondrial apoptosis induced by celastrol in APL cells. Celastrol shows great potential for the treatment of APL. PMID- 27374098 TI - Measuring PC activity in endocervical swab may provide a simple and non-invasive method to detect endometrial cancer in post-menopausal women. AB - Endometrial cancer is one of the most common gynecological malignancies in post menopausal women. If detected at early stages, endometrial cancer can be effectively treated by abdominal hysterectomy. However, to date, there is no biochemical test available for early and easy detection of endometrial cancer. Our previous study has established that the total proprotein convertase (PC) activity is significantly increased in the uterine lavage of post-menopausal women with endometrial cancer. Uterine lavage can be obtained relatively non invasively compared to uterine tissues, however, blood contamination and other factors limit the wide clinical use of uterine lavage. The aim of this study was to determine whether endocervical swab is a viable alternative to uterine lavage for the detection of endometrial cancer. We determined the correlation in PC activity between paired endocervical swabs and uterine lavages from individual post-menopausal women (control as well as endometrial cancer patients), and also compared the total PC activity in endocervical swabs between control and endometrial cancer patients. Our data demonstrated that the total PC activity in swab and lavage was highly correlative in post-menopausal women, and that the PC activity in endocervical swab was significantly increased in endometrial cancer patients compared to controls. These results strongly suggest that determining PC activity in endocervical swabs may provide a simple, non-invasive and novel method to detect endometrial cancer in post-menopausal women. PMID- 27374101 TI - Circulating tumor cells (CTCs) are associated with abnormalities in peripheral blood dendritic cells in patients with inflammatory breast cancer. AB - CTCs are involved in tumor dissemination and are an independent prognostic factor in primary and metastatic breast cancer patients. Dendritic cells (DCs) are the most efficient antigen presenting cells and are comprised of plasmacytoid-(pDC) and myeloid-(mDC) derived DC subsets. This study aimed to correlate CTC counts with the peripheral blood DC immunophenotypes and functions of inflammatory breast cancer (IBC) patients. This study included 65 IBC patients. Peripheral blood (PB) was obtained from patients prior to starting a new line of chemotherapy for CTCs enumeration by CellSearch(r) and DC phenotype and function by flow cytometry; the characteristics of DCs were then correlated with CTC counts and clinical outcome. Twenty-one (32.3%) patients with CTCs >=5 had a significantly inferior overall survival (OS) compared to patients with <5 CTCs (p=0.045). In addition, patients with >=5 CTCs had a lower percentage of mDCs capable of producing TNF-alpha before or after activation through the toll-like receptor (TLR), as well as a lower percentage of mDCs producing IL-12 after TLR activation. There was a positive correlation between CTCs counts and expression of the activation (CCR7) and costimulatory (CD86) receptors on TLR-activated mDCs and pDCs, respectively. Moreover, presence of high percentage of mDC capable to produce increased levels of TNF-alpha was independently associated with inferior OS (p = 0.0006). An increase in the percentage of mDC producing TNF-alpha might induce a pro-inflammatory environment that could play a role in determining the poor clinical outcome in IBC patients and could add further prognostic value to CTCs. PMID- 27374102 TI - Analysis of tissue and circulating microRNA expression during metaplastic transformation of the esophagus. AB - Genetic changes involved in the metaplastic progression from squamous esophageal mucosa toward Barrett's metaplasia and adenocarcinoma are almost unknown. Several evidences suggest that some miRNAs are differentially expressed in Barrett's esophagus (BE) and esophageal adenocarcinoma. Among these, miR-143, miR-145, miR 194, miR-203, miR-205, miR-215 appear to have a key role in metaplasia and neoplastic progression. The aim of this study was to analyze deregulated miRNAs in serum and esophageal mucosal tissue biopsies to identify new biomarkers that could be associated with different stages of esophageal disease. Esophageal mucosal tissue biopsies and blood samples were collected and analyzed for BE diagnosis. Quantitative Real-time PCR was used to compare miRNA expression levels in serum and 60 disease/normal-paired tissues from 30 patients diagnosed with esophagitis, columnar-lined esophagus (CLO) or BE. MiRNA expression analysis showed that miR-143, miR-145, miR-194 and miR-215 levels were significantly higher, while miR-203 and miR-205 were lower in BE tissues compared with their corresponding normal tissues. Esophageal mucosa analysis of patients with CLO and esophagitis showed that these miRNAs were similarly deregulated but to a lesser extent keeping the same trend and CLO appeared as intermediate step between esophagitis and BE. Analysis on circulating miRNA levels confirmed that miR-194 and miR-215 were significantly upregulated in both BE and CLO compared to esophagitis, while miR-143 was significantly upregulated only in the Barrett group. These findings suggest that miRNAs may be involved in neoplastic/metaplastic progression and miRNA analysis might be useful for progression risk prediction as well as for monitoring of BE/CLO patients. PMID- 27374103 TI - Antitumor efficacy of the heparan sulfate mimic roneparstat (SST0001) against sarcoma models involves multi-target inhibition of receptor tyrosine kinases. AB - The heparan sulfate (HS) mimic/heparanase inhibitor roneparstat (SST0001) shows antitumor activity in preclinical sarcoma models. We hypothesized that this 100% N-acetylated and glycol-split heparin could interfere with the functions of several receptor tyrosine kinases (RTK) coexpressed in sarcomas and activated by heparin-binding growth factors. Using a phospho-proteomic approach, we investigated the drug effects on RTK activation in human cell lines representative of different sarcoma subtypes. Inhibition of FGF, IGF, ERBB and PDGF receptors by the drug was biochemically and functionally validated. Roneparstat counteracted the autocrine loop induced by the COL1A1/PDGFB fusion oncogene, expressed in a human dermatofibrosarcoma protuberans primary culture and in NIH3T3COL1A1/PDGFB transfectants, inhibiting cell anchorage-independent growth and invasion. In addition, roneparstat inhibited the activation of cell surface PDGFR and PDGFR-associated FAK, likely contributing to the reversion of NIH3T3COL1A1/PDGFB cell transformed and pro-invasive phenotype. Biochemical and histological/immunohistochemical ex vivo analyses confirmed a reduced activation of ERBB4, EGFR, INSR, IGF1R, associated with apoptosis induction and angiogenesis inhibition in a drug-treated Ewing's sarcoma family tumor xenograft. The combination of roneparstat with irinotecan significantly improved the antitumor effect against A204 rhabdoid xenografts resulting in a high rate of complete responses and cures. These findings reveal that roneparstat exerts a multi-target inhibition of RTKs relevant in the pathobiology of different sarcoma subtypes. These effects, likely cooperating with heparanase inhibition, contribute to the antitumor efficacy of the drug. The study supports heparanase/HS axis targeting as a valuable approach in combination therapies of different sarcoma subtypes providing a preclinical rationale for clinical investigation. PMID- 27374104 TI - RPL27A is a target of miR-595 and may contribute to the myelodysplastic phenotype through ribosomal dysgenesis. AB - We investigated the functional consequences following deletion of a microRNA (miR) termed miR-595 which resides on chromosome 7q and is localised within one of the commonly deleted regions identified for Myelodysplasia (MDS) with monosomy 7 (-7)/isolated loss of 7q (7q-). We identified several targets for miR-595, including a large ribosomal subunit protein RPL27A. RPL27A downregulation induced p53 activation, apoptosis and inhibited proliferation. Moreover, p53-independent effects were additionally identified secondary to a reduction in the ribosome subunit 60s. We confirmed that RPL27A plays a pivotal role in the maintenance of nucleolar integrity and ribosomal synthesis/maturation. Of note, RPL27A overexpression, despite showing no significant effects on p53 mRNA levels, did in fact enhance cellular proliferation. In normal CD34+ cells, RPL27A knockdown preferentially blocked erythroid proliferation and differentiation. Lastly, we show that miR-595 expression appears significantly downregulated in the majority of primary samples derived from MDS patients with (-7)/(7q-), in association with RPL27A upregulation. This significant downregulation of miR-595 is also apparent when higher risk MDS cases are compared to lower risk cases. The potential clinical importance of these findings requires further validation. PMID- 27374105 TI - The essential role of GATA transcription factors in adult murine prostate. AB - GATA transcription factors are essential in mammalian cell lineage determination and have a critical role in cancer development. In cultured prostate cancer cells, GATA2 coordinates with androgen receptor (AR) to regulate gene transcription. In the murine prostate, among six GATA members, GATA2 and GATA3 are expressed. Immunofluorescence staining revealed that both GATA factors predominantly localize in the nuclei of luminal epithelial cells. The pioneer factor FoxA1 is exclusively detected in the luminal cells, whereas AR is detected in both luminal and basal cells. Using genetic engineering, we generated prostate specific GATA2 and GATA3 knockout (KO) mice. Ablation of single GATA gene had marginal effect on prostate morphology and AR target gene expression, likely due to their genetic compensation. Double KO mice exhibited PIN III to IV lesions, but decreased prostate to body weight ratio, altered AR target gene expression, and expansion of p63-positive basal cells. However, deletion of GATA2 and GATA3 did not reduce the mRNA or protein levels of AR or FoxA1, indicating that GATA factors are not required for AR or FoxA1 expression in adult prostate. Surprisingly, GATA2 and GATA3 exhibit minimal expression in the ventral prostatic (VP) lobe. In contrast, FoxA1 and AR expression levels in VP are at least as high as those in anterior prostatic (AP) and dorsal-lateral prostatic (DLP) lobes. Together, our results indicate that GATA2 and GATA3 are essential for adult murine prostate function and in vivo AR signaling, and the lack of the GATA factor expression in the VP suggests a fundamental difference between VP and other prostatic lobes. PMID- 27374106 TI - TP53 codon 72 polymorphism may predict early tumour progression in paediatric pilocytic astrocytoma. AB - Pilocytic astrocytoma and ganglioglioma may occur in inaccessible or surgically difficult areas. In case of incomplete resection, the availability of biological predictors of tumour progression could be particularly important. To this end, an analysis of p53 codon 72 polymorphism and assessment of its role as prognostic marker were performed.The status of the p53 Arg72Pro polymorphism was evaluated by pyrosequencing method in a multicenter cohort of 170 paediatric patients. Genotype/phenotype associations were investigated either by means of bivariate or multivariate analyses.In the partially resected pilocytic astrocytomas, the Arg/Arg variant predicts early tumour progression (median survival time: 23.1 months) and is associated with poor event-free survival (p value = 0.0009). This finding remains true also in case of adjuvant therapies, with a 5-year event-free survival of 30.6% for cases with Arg/Arg variant vs. 78.7% for those with other genotypes. There is no association between ganglioglioma and the polymorphism.The assessment of Arg/Arg variant could improve the management of pilocytic astrocytoma. TP53 codon 72 analysis could distinguish low-risk cases, in which surgery could be conservative, from high-risk cases needing an aggressive surgery plan. PMID- 27374108 TI - Genetic variants in regulatory regions of microRNAs are associated with lung cancer risk. AB - Genetic variants in regulatory regions of some miRNAs might be associated with lung cancer risk and survival. We performed a case-control study including 1341 non-small cell lung cancer (NSCLC) cases and 1982 controls to evaluate the associations of 7 potentially functional polymorphisms in several differently expressed miRNAs with NSCLC risk. Each SNP was also tested for the association with overall survival of 1001 NSCLC patients. We identified that rs9660710 in miR 200b/200a/429 cluster and rs763354 in miR-30a were significantly associated with NSCLC risk [odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.06-1.30, P = 0.002; OR = 0.88, 95% CI = 0.80-0.98, P = 0.017; respectively]. However, no significant association between variants and NSCLC death risk was observed in survival analysis. Functional annotation showed that both rs9660710 and rs763354 were located in regulatory elements in lung cancer cells. Compared to normal tissues, miR-200a-3p, miR-200a-5p, miR-200b-3p, miR-200b-5p and miR-429 were significantly increased in The Cancer Genome Atlas (TCGA) Lung Adenocarcinoma (LUAD) tumors, whereas miR-30a-3p and miR-30a-5p were significantly decreased in tumors (all P < 0.05). Furthermore, we observed that rs9660710 is an expression quantitative trait locus (eQTL) or methylation eQTL for miR-429 expression in TCGA normal tissues. Our results indicated that rs9660710 in miR-200b/200a/429 cluster and rs763354 in miR-30a might modify the susceptibility to NSCLC. PMID- 27374109 TI - Indications for embolization in a French level 1 trauma center. AB - Abdominal trauma accounts for nearly 20% of all traumatic injuries. It often involves young patients sustaining multiple injuries, with a high associated mortality rate. Management should begin at the scene of injury and relies on a structured chain of care in order to transport the trauma patient to the appropriate hospital center. Management is multi-disciplinary, involving intensive care specialists, surgeons and radiologists. Imaging to precisely define injury is best performed with whole body dual phase computed tomography, which can also identify the source of bleeding. Non-operative management has developed considerably over the years: this includes selective embolization in case of active bleeding or vascular anomalies in stable or stabilized patients after resuscitation. Embolization has become one of the corner stones of abdominal trauma management and interventional radiologists must play an active role on the trauma team. This overview details the different embolization procedures according to the involved organ and embolic agent used. PMID- 27374110 TI - Frailty and postoperative outcomes in patients undergoing surgery for degenerative spine disease. AB - BACKGROUND CONTEXT: Frailty is defined as a state of decreased reserve and susceptibility to stressors. The relationship between frailty and postoperative outcomes after degenerative spine surgery has not been studied. PURPOSE: This study aimed to (1) determine prevalence of frailty in the degenerative spine population; (2) describe patient characteristics associated with frailty; and (3) determine the association between frailty and postoperative complications, mortality, length of stay, and discharge disposition. STUDY DESIGN: This is a retrospective analysis on a prospectively collected cohort from the National Surgical Quality Improvement Program (NSQIP). PATIENT SAMPLE: A total of 53,080 patients who underwent degenerative spine surgery between 2006 and 2012 were included in the study. OUTCOME MEASURES: A modified frailty index (mFI) with 11 variables derived from the NSQIP dataset was used to determine prevalence of frailty and its correlation with a composite outcome of perioperative complications as well as hospital length of stay, mortality, and discharge disposition. METHODS: After calculating the mFI for each patient, the prevalence and predictors of frailty were determined for our cohort. The association of frailty with postoperative outcomes was determined after adjusting for known and suspected confounders using multivariate logistic regression. RESULTS: Frailty was present in 2,041 patients within the total population (4%) and in 8% of patients older than 65 years. Frailty severity increased with increasing age, male sex, African American race, higher body mass index, recent weight loss, paraplegia or quadriplegia, American Society of Anesthesiologists (ASA) score, and preadmission residence in a care facility. Frailty severity was an independent predictor of major complication (OR 1.15 for every 0.10 increase in mFI, 95%CI 1.09-1.21, p<.0005) and specifically predicted reoperation for postsurgical infection (OR 1.3, 95%CI 1.16-1.46, p<.0005). Prolonged length of stay and discharge to a new facility were also independently predicted by frailty severity (p<.0005). Frailty severity predicted 30-day mortality on unadjusted (OR 2.05, 95%CI 1.70-2.48, p<.0005) and adjusted analyses (OR 1.48, 95%CI 1.18-1.86, p<.0005). CONCLUSIONS: Frailty is an important predictor of postoperative outcomes following degenerative spine surgery. Preoperative recognition of frailty may be useful for perioperative optimization, risk stratification, and patient counseling. PMID- 27374111 TI - Percutaneous vertebroplasty: a new animal model. AB - BACKGROUND CONTEXT: Percutaneous vertebroplasty (PVP) is a minimally invasive surgical procedure and is frequently performed in humans who need surgical treatment of vertebral fractures. PVP involves cement injection into the vertebral body, thereby providing rapid and significant pain relief. PURPOSE: The testing of novel biomaterials depends on suitable animal models. The aim of this study was to develop a reproducible and safe model of PVP in sheep. STUDY DESIGN: This study used ex vivo and in vivo large animal model study (Merino sheep). METHODS: Ex vivo vertebroplasty was performed through a bilateral modified parapedicular access in 24 ovine lumbar hemivertebrae, divided into four groups (n=6). Cerament (Bone Support, Lund, Sweden) was the control material. In the experimental group, a novel composite was tested-Spine-Ghost-which consisted of an alpha-calcium sulfate matrix enriched with micrometric particles of mesoporous bioactive glass. All vertebrae were assessed by micro-computed tomography (micro CT) and underwent mechanical testing. For the in vivo study, 16 sheep were randomly allocated into control and experimental groups (n=8), and underwent PVP using the same bone cements. All vertebrae were assessed postmortem by micro-CT, histology, and reverse transcription-polymerase chain reaction (rt-PCR). This work has been supported by the European Commission under the 7th Framework Programme for collaborative projects (600,000-650,000 USD). RESULTS: In the ex vivo model, the average defect volume was 1,275.46+/-219.29 mm3. Adequate defect filling with cement was observed. No mechanical failure was observed under loads which were higher than physiological. In the in vivo study, cardiorespiratory distress was observed in two animals, and one sheep presented mild neurologic deficits in the hind limbs before recovering. CONCLUSIONS: The model of PVP is considered suitable for preclinical in vivo studies, mimicking clinical application. All sheep recovered and completed a 6-month implantation period. There was no evidence of cement leakage into the vertebral foramen in the postmortem examination. PMID- 27374112 TI - Evaluation of an injectable hydrogel and polymethyl methacrylate in restoring mechanics to compressively fractured spine motion segments. AB - BACKGROUND CONTEXT: Compressive fracture can produce profound changes to the mechanical profile of a spine segment. Minimally invasive repair has the potential to restore both function and structural integrity to an injured spine. Use of both hydrogels to address changes to the disc, combined with polymethyl methacrylate (PMMA) to address changes to the vertebral body, has the potential to facilitate repair. PURPOSE: The purpose of this investigation was to determine if the combined use of hydrogel injection and PMMA could restore the mechanical profile of an axially injured spinal motion segment. STUDY DESIGN: This is a basic science study evaluating a combination of hydrogel injection and vertebroplasty on restoring mechanics to compressively injured porcine spine motion segments. METHODS: Fourteen porcine spine motion segments were subject to axial compression until fracture using a dynamic servohydraulic testing apparatus. Rotational and compressive stiffness was measured for each specimen under the following conditions: initial undamaged, fractured, fatigue loading under compression, hydrogel injection, PMMA injection, and fatigue loading under compression. Group 1 received hydrogel injection followed by PMMA injection, whereas Group 2 received PMMA injection followed by hydrogel injection. This study was funded under a Natural Sciences and Engineering Research Council of Canada discovery grant. RESULTS: PMMA injection was found to alter the compressive stiffness properties of axially injured spine motion segments, restoring values from Groups 1 and 2 to 89.3%+/-29.3% and 81%+/-27.9% of initial values respectively. Hydrogel injection was found to alter the rotational stiffness properties, restoring specimens in Groups 1 and 2 to 151.5%+/-81% and 177.2%+/-54.9% of initial values respectively. Prolonged restoration of function was not possible, however, after further fatigue loading. CONCLUSIONS: Using this repair technique, replication of the mechanism of injury appears to cause a rapid deterioration in function of the motion segments. Containment of the hydrogel appears to be an issue with large breaches in the end plate, as it is posited to migrate into the cancellous bone of the vertebral body. Future work should attempt to evaluate methods in fully sealing the disc space. PMID- 27374113 TI - Rodent spinal cord injury models for studies of axon regeneration. AB - For over a century, axon regeneration has been considered the Holy Grail for spinal cord injury (SCI) repair. Although there are other factors that could contribute to improving function, restoring the long motor and sensory tracts that are interrupted by SCI has the greatest potential for actually reversing paralysis, restoring the brain's control of autonomic functions mediated by sympathetic and parasympathetic circuits of the spinal cord and restoring sensation. Accordingly and in keeping with the overall theme of this special issue, this review focuses narrowly on rodent SCI models for studies of axon regeneration. PMID- 27374114 TI - IL-15 up-regulates the MMP-9 expression levels and induces inflammatory infiltration of macrophages in polymyositis through regulating the NF-kB pathway. AB - This study was aimed to research the effects of IL-15 on inducing inflammatory infiltration of macrophages in polymyositis (PM) through the NF-kB pathway, and whether IL-15 was able to further regulate MMP-9 expression levels. Prepared PM cells, collected from the patients suffering from PM, were administered to SD rats. Also, a group of healthy SD rats was undergoing the same treatment as the control group. The test animals were treated with either anti-IL-15, IL-15, MMP-9 siRNA or ERK1/2 inhibitor. The blood toxicological parameters creatine kinase (CK) and CD163 were tested by using ELISA and immunohistochemistry assay. In addition, NF-kB expression in macrophages was measured by immunocytochemical assay. To measure the degree of cell infiltration the Transwell assay was performed. Lastly, western blot and zymography were carried out to compare MMP-9 and ERK expression levels between the two groups, both in vivo and in vitro. The results showed that S-CK, IL-15 and IL-15Ralpha levels increased rapidly after the conventional treatment was introduced to the PM infected SD rats. The PM model establishment and IL-15 treatment significantly increased the expressions of IL-15Ralpha, MMP-9, p-ERK and p-IKBalpha. However, the same effect can be suppressed by using anti-IL-15, MMP-9 siRNA or ERK1/2 inhibitor (P < 0.05). In addition, IL-15 is proved to increase cell migration and nucleus expression of NF kB in the macrophages. IL-15 is able to significantly regulate the inflammatory infiltration of macrophages in PM patients through affecting the NF-kB pathway and MMP-9 expression levels. PMID- 27374115 TI - Unrelated Future Costs and Unrelated Future Benefits: Reflections on NICE Guide to the Methods of Technology Appraisal. AB - In this editorial, we consider the vexing issue of 'unrelated future costs' (for example, the costs of caring for people with dementia or kidney failure after preventing their deaths from a heart attack). The National Institute of Health and Care Excellence (NICE) guidance is not to take such costs into account in technology appraisals. However, standard appraisal practice involves modelling the benefits of those unrelated technologies. We argue that there is a sound principled reason for including both the costs and benefits of unrelated care. Changing this practice would have material consequences for decisions about reimbursing particular technologies, and we urge future research to understand this better. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27374116 TI - Identification of a novel HLA-B null allele, HLA-B*41:45N, by HLA typing of two related Caucasoid individuals. AB - The new HLA-B*41:45N allele differs from B*41:02 by insertion of 21 nucleotides in exon 2. PMID- 27374117 TI - Vitamin D controls resistance artery function through regulation of perivascular adipose tissue hypoxia and inflammation. AB - Vitamin D deficiency in human subjects is associated with hypertension, metabolic syndrome and related risk factors of cardiovascular diseases. Serum 25 hydroxyvitamin D levels correlate inversely with adiposity in obese and lean individuals. Bioactive vitamin D, or calcitriol, exerts anti-inflammatory effects on adipocytes, preadipocytes and macrophages in vitro. We tested the hypothesis that vitamin D deficiency alters the phenotype of perivascular adipose tissue (PVAT) leading to impaired function in resistance artery. To examine the effects of vitamin D and PVAT on vascular reactivity, myograph experiments were performed on arteries, with or without intact PVAT, from mice maintained on vitamin D deficient, vitamin D-sufficient or vitamin D-supplemented diet. Systolic blood pressure was significantly increased in mice on vitamin D-deficient diet. Importantly, vitamin D deficiency enhanced angiotensin II-induced vasoconstriction and impaired the normal ability of PVAT to suppress contractile responses of the underlying mesenteric resistance artery to angiotensin II and serotonin. Furthermore, vitamin D deficiency caused upregulation of the mRNA expression of tumor necrosis factor-alpha, hypoxia-inducible factor-1alpha and its downstream target lysyl oxidase in mesenteric PVAT. Incubation of mesenteric arteries under hypoxic conditions impaired the anti-contractile effects of intact PVAT on those arteries from mice on vitamin D-sufficient diet. Vitamin D supplementation protected arteries against hypoxia-induced impairment of PVAT function. The protective effects of vitamin D against vascular dysfunction, hypertension and cardiovascular diseases may be mediated, at least in part, through regulation of inflammatory and hypoxia signaling pathways in PVAT. PMID- 27374118 TI - A dipeptidyl peptidase-4 inhibitor ameliorates hypertensive cardiac remodeling via angiotensin-II/sodium-proton pump exchanger-1 axis. AB - BACKGROUND: To address the impact of antidiabetic drugs on cardiovascular safety is a matter of clinical concern. Preclinical studies revealed that various protective effects of dipeptidyl peptidase-4 inhibitor (DPP4i) on cardiovascular disease; however, its impact of on hypertension remains controversial. METHODS AND RESULTS: Teneligliptin (TEN; 10mg/kg/day/p.o.) ameliorates hypertension and cardiac remodeling by normalizing a rise of angiotensin-II (AngII) that specifically observed in spontaneously hypertensive rats (SHR). TEN had no effects on vasculature and concentrations of the DPP4-related vasoactive peptides (bradykinin, neuropeptide Y, and atrial natriuretic peptide). The primary action of TEN on BP lowering was due to restoring the AngII-induced manifestation of congestive heart failure observed in SHR. Sodium-proton pump exchanger type 1 (NHE-1) is a regulator of intracellular acidity (pHi) and implicated pathophysiological role in cardiac remodeling occurred in diseased myocardium. Cardiac NHE-1 expression level was increased in SHR and this was restored in TEN treated SHR. AngII directly augmented cardiac NHE-1 expression and its activity that contributed to hypertrophic response. TEN attenuated the AngII-induced cardiac hypertrophy with decline in pHi via suppression of NHE-1. Loss of NHE-1 activity by specific inhibitor or RNA silencing promoted intracellular acidification and consistently attenuated the AngII-mediated cardiac hypertrophy. CONCLUSION: The present study revealed the protective actions of TEN on hypertension and comorbid cardiac remodeling via AngII/NHE-1 axis and the novel pathophysiological roles of intracellular acidification via NHE-1 in cardiac hypertrophy. PMID- 27374119 TI - neXtA5: accelerating annotation of articles via automated approaches in neXtProt. AB - The rapid increase in the number of published articles poses a challenge for curated databases to remain up-to-date. To help the scientific community and database curators deal with this issue, we have developed an application, neXtA5, which prioritizes the literature for specific curation requirements. Our system, neXtA5, is a curation service composed of three main elements. The first component is a named-entity recognition module, which annotates MEDLINE over some predefined axes. This report focuses on three axes: Diseases, the Molecular Function and Biological Process sub-ontologies of the Gene Ontology (GO). The automatic annotations are then stored in a local database, BioMed, for each annotation axis. Additional entities such as species and chemical compounds are also identified. The second component is an existing search engine, which retrieves the most relevant MEDLINE records for any given query. The third component uses the content of BioMed to generate an axis-specific ranking, which takes into account the density of named-entities as stored in the Biomed database. The two ranked lists are ultimately merged using a linear combination, which has been specifically tuned to support the annotation of each axis. The fine-tuning of the coefficients is formally reported for each axis-driven search. Compared with PubMed, which is the system used by most curators, the improvement is the following: +231% for Diseases, +236% for Molecular Functions and +3153% for Biological Process when measuring the precision of the top-returned PMID (P0 or mean reciprocal rank). The current search methods significantly improve the search effectiveness of curators for three important curation axes. Further experiments are being performed to extend the curation types, in particular protein-protein interactions, which require specific relationship extraction capabilities. In parallel, user-friendly interfaces powered with a set of JSON web services are currently being implemented into the neXtProt annotation pipeline.Available on: http://babar.unige.ch:8082/neXtA5Database URL: http://babar.unige.ch:8082/neXtA5/fetcher.jsp. PMID- 27374121 TI - HPIDB 2.0: a curated database for host-pathogen interactions. AB - Identification and analysis of host-pathogen interactions (HPI) is essential to study infectious diseases. However, HPI data are sparse in existing molecular interaction databases, especially for agricultural host-pathogen systems. Therefore, resources that annotate, predict and display the HPI that underpin infectious diseases are critical for developing novel intervention strategies. HPIDB 2.0 (http://www.agbase.msstate.edu/hpi/main.html) is a resource for HPI data, and contains 45, 238 manually curated entries in the current release. Since the first description of the database in 2010, multiple enhancements to HPIDB data and interface services were made that are described here. Notably, HPIDB 2.0 now provides targeted biocuration of molecular interaction data. As a member of the International Molecular Exchange consortium, annotations provided by HPIDB 2.0 curators meet community standards to provide detailed contextual experimental information and facilitate data sharing. Moreover, HPIDB 2.0 provides access to rapidly available community annotations that capture minimum molecular interaction information to address immediate researcher needs for HPI network analysis. In addition to curation, HPIDB 2.0 integrates HPI from existing external sources and contains tools to infer additional HPI where annotated data are scarce. Compared to other interaction databases, our data collection approach ensures HPIDB 2.0 users access the most comprehensive HPI data from a wide range of pathogens and their hosts (594 pathogen and 70 host species, as of February 2016). Improvements also include enhanced search capacity, addition of Gene Ontology functional information, and implementation of network visualization. The changes made to HPIDB 2.0 content and interface ensure that users, especially agricultural researchers, are able to easily access and analyse high quality, comprehensive HPI data. All HPIDB 2.0 data are updated regularly, are publically available for direct download, and are disseminated to other molecular interaction resources.Database URL: http://www.agbase.msstate.edu/hpi/main.html. PMID- 27374123 TI - Sphingomonaszeicaulis sp. nov., an endophytic bacterium isolated from maize root. AB - A novel Gram-staining-negative, aerobic and rod-shaped strain designated 541T was isolated from surface-sterilized root tissue of maize, collected from the Fangshan District of Beijing, People's Republic of China, and was subjected to a taxonomic study using a polyphasic approach. According to a phylogenetic tree based on 16S rRNA gene sequences, strain 541T represented a member of the genus Sphingomonas and clustered with Sphingomonas sanxanigenens DSM 19645T, with which it shared the highest 16S rRNA gene sequence similarity (98.8 %). The predominant respiratory quinone was ubiquinone-10 (Q-10), the major polyamine was sym homospermidine and the major cellular fatty acids were C18 : 1omega7c (50.9 %), C16 : 0 (22.0 %) and C14 : 0 2-OH (11.4 %). The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine and sphingoglycolipid. The DNA G+C content was 64.7 mol%. DNA DNA relatedness between strain 541T and its closest phylogenetic relative Sphingomonas sanxanigenens DSM 19645T was 50.8 %. The results of physiological and biochemical tests and the differences in the fatty acid profiles allowed a clear phenotypic differentiation of strain 541T from closely related species of the genus Sphingomonas. Strain 541T represents a novel species within the genus Sphingomonas, for which the nameSphingomonas zeicaulis sp. nov. is proposed, with the type strain 541T (=CGMCC 1.15008T=DSM 100587T). PMID- 27374122 TI - Coreference resolution improves extraction of Biological Expression Language statements from texts. AB - We describe a system that automatically extracts biological events from biomedical journal articles, and translates those events into Biological Expression Language (BEL) statements. The system incorporates existing text mining components for coreference resolution, biological event extraction and a previously formally untested strategy for BEL statement generation. Although addressing the BEL track (Track 4) at BioCreative V (2015), we also investigate how incorporating coreference resolution might impact event extraction in the biomedical domain. In this paper, we report that our system achieved the best performance of 20.2 and 35.2 in F-score for the full BEL statement level on both stage 1, and stage 2 using provided gold standard entities, respectively. We also report that our results evaluated on the training dataset show benefit from integrating coreference resolution with event extraction. PMID- 27374124 TI - New perspectives for multi-level regulations of neuronal acetylcholinesterase by dioxins. AB - Acetylcholinesterase (AChE; EC 3.1.1.7) is a vital functional enzyme in cholinergic neurotransmission which can rapidly hydrolyze neurotransmitter, acetylcholine, in the central and peripheral nervous systems. Emerging evidence showed that in addition to classical environmental AChE inhibitors, e.g. organophosphate and carbamate pesticides, dioxins are a new type of xenobiotic causing impairment of AChE. Dioxin can transcriptionally or post transcriptionally suppress AChE expression in human neuroblastoma cells or mouse immune cells via the aryl hydrocarbon receptor (AhR) pathway, respectively. Dioxins can affect gene expression through other mechanisms, such as cross-talk with other signaling cascades and epigenetic modulations. Therefore, in this review, by summarizing the known mechanisms of AChE regulation and dioxin-induced gene alteration, potential signaling cascades and epigenetic mechanisms are proposed for dioxin-mediated AChE regulation. Mitogen activated protein (MAP) kinase, 3', 5'-cyclic adenosine monophosphate (cAMP) and calcium-related singaling pathways, as well as potential epigenetic mechanisms, such as DNA methylation, and post-transcriptional regulation via microRNAs, including hsa-miR 132, hsa-miR-212 and hsa-miR-25-3p are discussed here. These proposed mechanisms may be invaluable not only to promote comprehensive understanding of the action mechanisms for dioxin, but to illustrate the molecular basis of dioxin-induced health impacts. PMID- 27374120 TI - The harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins. AB - Genomics, epigenomics, transcriptomics, proteomics and metabolomics efforts rapidly generate a plethora of data on the activity and levels of biomolecules within mammalian cells. At the same time, curation projects that organize knowledge from the biomedical literature into online databases are expanding. Hence, there is a wealth of information about genes, proteins and their associations, with an urgent need for data integration to achieve better knowledge extraction and data reuse. For this purpose, we developed the Harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins from over 70 major online resources. We extracted, abstracted and organized data into ~72 million functional associations between genes/proteins and their attributes. Such attributes could be physical relationships with other biomolecules, expression in cell lines and tissues, genetic associations with knockout mouse or human phenotypes, or changes in expression after drug treatment. We stored these associations in a relational database along with rich metadata for the genes/proteins, their attributes and the original resources. The freely available Harmonizome web portal provides a graphical user interface, a web service and a mobile app for querying, browsing and downloading all of the collected data. To demonstrate the utility of the Harmonizome, we computed and visualized gene-gene and attribute-attribute similarity networks, and through unsupervised clustering, identified many unexpected relationships by combining pairs of datasets such as the association between kinase perturbations and disease signatures. We also applied supervised machine learning methods to predict novel substrates for kinases, endogenous ligands for G-protein coupled receptors, mouse phenotypes for knockout genes, and classified unannotated transmembrane proteins for likelihood of being ion channels. The Harmonizome is a comprehensive resource of knowledge about genes and proteins, and as such, it enables researchers to discover novel relationships between biological entities, as well as form novel data-driven hypotheses for experimental validation.Database URL: http://amp.pharm.mssm.edu/Harmonizome. PMID- 27374127 TI - Machine learning for medical images analysis. AB - This article discusses the application of machine learning for the analysis of medical images. Specifically: (i) We show how a special type of learning models can be thought of as automatically optimized, hierarchically-structured, rule based algorithms, and (ii) We discuss how the issue of collecting large labelled datasets applies to both conventional algorithms as well as machine learning techniques. The size of the training database is a function of model complexity rather than a characteristic of machine learning methods. PMID- 27374126 TI - Critical analysis of molluscicide application in schistosomiasis control programs in Brazil. AB - In Brazil, Biomphalaria glabrata, B. tenagophila, and B. straminea are naturally infected by the trematode Schistosoma mansoni, the causative agent of schistosomiasis. Despite decades of governmental efforts through official control programs, schistosomiasis remains an important public health problem in the country: thousands of people are infected with the trematode each year and millions live in endemic areas. The World Health Organization recommends using a combination of molluscicide (niclosamide) and mass chemotherapy to control the transmission of schistosomiasis, with this treatment successfully reducing the morbidity of the disease. In the past, niclosamide has been used in official schistosomiasis control programs in Brazil. However, as B. glabrata recolonizes even after molluscicide application, the use of molluscicides has gradually decreased in the country until they were discontinued in 2002, mainly due to the rising global pressure to preserve the environment and the difficulties of obtaining licenses from the Brazilian Ministry of Environment to use toxic substances in aquatic ecosystems. Therefore, the discovery of new molluscicides, which could be more selective to Biomphalaria species and less harmful to the aquatic ecosystem, is necessary. In addition, political efforts to sensitize funders to provide grants for this field of research are required. In this context, this article aims to make a critical analysis of molluscicide application in schistosomiasis control programs in Brazil. PMID- 27374128 TI - Imaging biomarkers in multiple Sclerosis: From image analysis to population imaging. AB - The production of imaging data in medicine increases more rapidly than the capacity of computing models to extract information from it. The grand challenges of better understanding the brain, offering better care for neurological disorders, and stimulating new drug design will not be achieved without significant advances in computational neuroscience. The road to success is to develop a new, generic, computational methodology and to confront and validate this methodology on relevant diseases with adapted computational infrastructures. This new concept sustains the need to build new research paradigms to better understand the natural history of the pathology at the early phase; to better aggregate data that will provide the most complete representation of the pathology in order to better correlate imaging with other relevant features such as clinical, biological or genetic data. In this context, one of the major challenges of neuroimaging in clinical neurosciences is to detect quantitative signs of pathological evolution as early as possible to prevent disease progression, evaluate therapeutic protocols or even better understand and model the natural history of a given neurological pathology. Many diseases encompass brain alterations often not visible on conventional MRI sequences, especially in normal appearing brain tissues (NABT). MRI has often a low specificity for differentiating between possible pathological changes which could help in discriminating between the different pathological stages or grades. The objective of medical image analysis procedures is to define new quantitative neuroimaging biomarkers to track the evolution of the pathology at different levels. This paper illustrates this issue in one acute neuro-inflammatory pathology: Multiple Sclerosis (MS). It exhibits the current medical image analysis approaches and explains how this field of research will evolve in the next decade to integrate larger scale of information at the temporal, cellular, structural and morphological levels. PMID- 27374129 TI - Role of Yb(3+) ions on enhanced ~2.9 MUm emission from Ho(3+) ions in low phonon oxide glass system. AB - The foremost limitation of an oxide based crystal or glass host to demonstrate mid- infrared emissions is its high phonon energy. It is very difficult to obtain radiative mid-infrared emissions from these hosts which normally relax non radiatively between closely spaced energy levels of dopant rare earth ions. In this study, an intense mid-infrared emission around 2.9 MUm has been perceived from Ho(3+) ions in Yb(3+)/Ho(3+) co-doped oxide based tellurite glass system. This emission intensity has increased many folds upon Yb(3+): 985 nm excitation compared to direct Ho(3+) excitations due to efficient excited state resonant energy transfer through Yb(3+): (2)F5/2 -> Ho(3+): (5)I5 levels. The effective bandwidth (FWHM) and cross-section (sigmaem) of measured emission at 2.9 MUm are assessed to be 180 nm and 9.1 * 10(-21) cm(2) respectively which are comparable to other crystal/glass hosts and even better than ZBLAN fluoride glass host. Hence, this Ho(3+)/Yb(3+) co-doped oxide glass system has immense potential for the development of solid state mid-infrared laser sources operating at 2.9 MUm region. PMID- 27374130 TI - Development of a method for the direct fermentation of semolina by selected sourdough lactic acid bacteria. AB - Three obligately heterofermentative lactic acid bacteria (LAB) strains (Lactobacillus sanfranciscensis PON100336, Leuconostoc citreum PON10079 and Weissella cibaria PON10030) were used in this study as a multi-species starter culture for sourdough production. The starter inoculum was prepared and propagated in sterile semolina extract (SSE) broth. Acidification kinetics, microbiological counts detected on specific media for sourdough LAB, polymorphic profile comparison and species-specific PCRs evidenced a stability of the liquid inoculum over time determining its suitability for direct addition to semolina. In order to validate this innovative method for the production of durum wheat (Triticum durum Desf) sourdoughs, 15 semolinas (from ten old and five modern genotypes cultivated in Sicily, southern Italy) were used to prepare the SSEs and to produce sourdoughs and finally breads. Chemical and microbiological analyses of the sourdoughs and the evaluation of the quality parameters (weight loss, height, crumb and crust colour, image analysis and volatile organic compound generation) of the resulting breads indicated that the direct addition of the liquid inocula propagated in SSE is a valuable method to stabilise the production of sourdoughs. The differences registered during the technological characterisation of the breads were underlined by the sensory tests and the multivariate analysis and are mainly imputable to the type of semolina. PMID- 27374132 TI - The psychoanalyst's normal and pathological superegos. AB - The first section of the paper explores a number of differing views regarding the concept of the superego, essentially in terms of its formation and its functions. Two broad theories of superego development, both of which were introduced by Freud, are described. The first takes the superego to be principally oedipal in origin; the second traces the superego to an earlier period. The controversy about the usefulness of the concept of the death instinct is also implicated in the different views. It is then suggested that it is worthwhile to distinguish between a normal superego and a pathological superego and that these two distinct models of the superego are implicit in the work of both Freud and Klein. Strachey's (1934) views on the nature of the mutative effect of psychoanalytic treatment are briefly reviewed in the light of this distinction. It is suggested that Strachey was hesitant in clarifying the full implications of his views, particularly regarding the reasons for the difficulty the psychoanalyst will experience in making a transference interpretation. It is argued that the difficulty will relate to the psychoanalyst's anxiety about having sufficiently worked through the countertransference, particularly in relation to superego functioning. Two brief clinical vignettes are considered in support of this view. The last section of the paper offers some comments on the emotional development of the psychoanalyst and the ways that maturing as a psychoanalyst will involve a certain mellowing of the analyst's stance and a greater tolerance of the patient's prerogative to bring the full range of his or her personality into the treatment. PMID- 27374131 TI - Frequency and trends of contact allergy to and iatrogenic contact dermatitis caused by topical drugs over a 25-year period. AB - BACKGROUND: Allergic contact dermatitis is the most common adverse reaction caused by topical drugs. OBJECTIVES: To study the demographic characteristics and lesion locations of patients with iatrogenic dermatitis, and to analyse contact allergy to active principles and trends in frequencies over the years. PATIENTS AND METHODS: Between 1990 and 2014, 14 911 patients were patch tested with the European baseline series. Patients with a presumed iatrogenic cause were often tested with a pharmaceutical series, and, if indicated, with photo-patch tests. Most were also tested with the topical products to which they had been exposed, along with their ingredients. RESULTS: Eight thousand three hundred and seventy four (56%) patients tested positively, and 2600 (17.4%, 95%CI: 16.8-18.0%) of all patients suffered from iatrogenic contact dermatitis. The most important primary sites of dermatitis were the legs, face, and hands. The most common sensitizers included topical antibiotics, antiseptics, and corticosteroids. The most frequent baseline allergens in this subgroup were budesonide, neomycin, and benzocaine, although with a decreasing trend over the years. Many other allergens from different pharmacological classes were identified. CONCLUSIONS: With a prevalence of 17.4% of consecutive patients, iatrogenic contact dermatitis is a frequent diagnosis in patients attending a general patch test clinic, involving one-third of the patients with at least one positive reaction. PMID- 27374133 TI - A Remote Role for Renalase. PMID- 27374134 TI - One-Step Modification of Electrode Surface for Ultrasensitive and Highly Selective Detection of Nucleic Acids with Practical Applications. AB - Electrochemistry-based nucleic acid sensors have long been plagued by the limited accessibility of target molecules to the capture probes immobilized on heterogeneous surfaces, which largely hinders their practical application. In this work, we find that dual-thiolated hairpin DNA immobilized on an electrode surface as the capture probe cannot only efficiently bind with target molecule as well as the signal probe but also process impressive protein-repelling ability, which allows us to directly detect as few as attomolar targets (~300 copies in 100 MUL sample) with single-base discrimination ability. Meanwhile, the preparation of functional electrode surface becomes simple (one step), fast (30 min), and homogeneous (just one probe modified surface without small molecules coassembled). These advantages are attributed to the unique probe design, where the stem of the capture probe can act as rigid scaffold to keep it upright, and the loop of the capture probe may provide an enclosed platform for target and signal probe binding. More importantly, through tuning the distance between enzyme and the electrode surface (from 8.5 to 13.6 nm), we find that the performance of the sensor can be favorably controlled. Furthermore, taking advantage of this new binding model, different complex samples including polymerase chain reaction (PCR) product, mRNA, and micro RNA can be conveniently analyzed, which may hold great potential for real application. PMID- 27374135 TI - Hair Cortisol and Its Association With Psychological Risk Factors for Psychiatric Disorders: A Pilot Study in Adolescent Twins. AB - Measuring cortisol in hair is a promising method to assess long-term alterations of the biological stress response system, and hair cortisol concentrations (HCC) may be altered in psychiatric disorders and in subjects suffering from chronic stress. However, the pattern of associations between HCC, chronic stress and mental health require clarification. Our exploratory study: (1) assessed the association between HCC and perceived stress, symptoms of depression and neuroticism, and the trait extraversion (as a control variable); and (2) made use of the twin design to estimate the genetic and environmental covariance between the variables of interest. Hair samples from 109 (74 female) subjects (age range 12-21 years, mean 15.1) including 8 monozygotic (MZ) and 21 dizygotic (DZ) twin pairs were analyzed. Perceived stress was measured with the Perceived Stress Scale and/or the Daily Life and Stressors Scale, neuroticism, and extraversion with the NEO-Five Factor Inventory or the Junior Eysenck Personality Questionnaire, and depressive symptoms with the Somatic and Psychological Health Report. We found a modest positive association between HCC and the three risk factors - perceived stress, symptoms of depression, and neuroticism (r = 0.22 0.33) - but no correlation with extraversion (-0.06). A median split revealed that the associations between HCC and risk factors were stronger (0.47-0.60) in those subjects with HCC >11.36 pg/mg. Furthermore, our results suggest that the genetic effects underlying HCC are largely shared with those that influence perceived stress, depressive symptoms, and neuroticism. These results of our proof of principle study warrant replication in a bigger sample but raise the interesting question of the direction of causation between these variables. PMID- 27374136 TI - The Effect of False-Positive Results on Subsequent Participation in Chest X-ray Screening for Lung Cancer. AB - BACKGROUND: High attendance rates and regular participation in disease screening programs are important contributors to program effectiveness. The objective of this study was to examine the effects of an initial false-positive result in chest X-ray screening for lung cancer on subsequent screening participation. METHODS: This historical cohort study analyzed individuals who first participated in a lung cancer screening program conducted by Yokohama City between April 2007 and March 2011, and these participants were retrospectively tracked until March 2013. Subsequent screening participation was compared between participants with false-positive results and those with negative results in evaluation periods between 365 (for the primary outcome) and 730 days. The association of screening results with subsequent participation was evaluated using a generalized linear regression model, with adjustment for characteristics of patients and screening. RESULTS: The proportions of subsequent screening participation within 365 days were 12.9% in 3132 participants with false-positive results and 6.7% in 15 737 participants with negative results. Although the differences in attendance rates were reduced with longer cutoffs, participants with false-positive results were consistently more likely to attend subsequent screening than patients with negative results (P < 0.01). The predictors of subsequent screening participation were false-positive results (risk ratio [RR] 1.72; 95% confidence interval [CI], 1.54-1.92), older age (RR 1.17; 95% CI, 1.11-1.23), male sex (RR 1.46; 95% CI, 1.29-1.64), being a current smoker (RR 0.80; 95% CI, 0.69-0.93), current employment (RR 0.79; 95% CI, 0.70-0.90), and being screened at a hospital cancer center (vs public health centers; RR 1.36; 95% CI, 1.15-1.60). CONCLUSIONS: Our findings indicated that subsequent participation in lung cancer screening was more likely among participants with false-positive results in an initial screening than patients with negative results. PMID- 27374137 TI - Iodine Excretion in 24-hour Urine Collection and Its Dietary Determinants in Healthy Japanese Adults. AB - BACKGROUND: Since seaweed is a common component of the Japanese diet, iodine intake in Japanese is expected to be high. However, urinary iodine excretion, measured using 24-hour urine samples, and its dietary determinants are not known. METHODS: Apparently healthy adults aged 20 to 69 years living in 20 areas throughout Japan were recruited in February and March, 2013. Urinary iodine excretion was evaluated using 24-hour urine collected from 713 subjects (362 men and 351 women), and the difference among age groups was assessed. The association between dietary intake of food groups and urinary iodine excretion was assessed among 358 subjects who completed a semi-weighed 4-day diet record (DR) and urine collection. The correlations between iodine intake and iodine excretion were also evaluated, and correlation coefficients were calculated for iodine intake in the DR of the overlapping day or the DR 1 day before and after urine collection. RESULTS: Median iodine excretion in 24-hour urine was 365 ug, and excretion was significantly higher in older subjects. Iodine intake estimated by the DRs was significantly correlated with urinary iodine excretion when DRs and urine collection were obtained on the same day (r = 0.37). After adjustment for confounding factors, iodine excretion was significantly associated with intakes of kelp and soup stock from kelp and fish. CONCLUSIONS: Although multiple measurements for urinary iodine are required to confirm our results, this study showed the current iodine status of healthy Japanese adults. The results suggest that kelp and fish are the main contributors to Japanese iodine status measured by 24-hour urine. PMID- 27374139 TI - Commentary The Importance of Cost Estimation for Molecular Epidemiology Studies. PMID- 27374140 TI - Reducing Research Waste Through Good Reporting Practices. PMID- 27374138 TI - The Tohoku Medical Megabank Project: Design and Mission. AB - The Great East Japan Earthquake (GEJE) and resulting tsunami of March 11, 2011 gave rise to devastating damage on the Pacific coast of the Tohoku region. The Tohoku Medical Megabank Project (TMM), which is being conducted by Tohoku University Tohoku Medical Megabank Organization (ToMMo) and Iwate Medical University Iwate Tohoku Medical Megabank Organization (IMM), has been launched to realize creative reconstruction and to solve medical problems in the aftermath of this disaster. We started two prospective cohort studies in Miyagi and Iwate Prefectures: a population-based adult cohort study, the TMM Community-Based Cohort Study (TMM CommCohort Study), which will recruit 80 000 participants, and a birth and three-generation cohort study, the TMM Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study), which will recruit 70 000 participants, including fetuses and their parents, siblings, grandparents, and extended family members. The TMM CommCohort Study will recruit participants from 2013 to 2016 and follow them for at least 5 years. The TMM BirThree Cohort Study will recruit participants from 2013 to 2017 and follow them for at least 4 years. For children, the ToMMo Child Health Study, which adopted a cross-sectional design, was also started in November 2012 in Miyagi Prefecture. An integrated biobank will be constructed based on the two prospective cohort studies, and ToMMo and IMM will investigate the chronic medical impacts of the GEJE. The integrated biobank of TMM consists of health and clinical information, biospecimens, and genome and omics data. The biobank aims to establish a firm basis for personalized healthcare and medicine, mainly for diseases aggravated by the GEJE in the two prefectures. Biospecimens and related information in the biobank will be distributed to the research community. TMM itself will also undertake genomic and omics research. The aims of the genomic studies are: 1) to construct an integrated biobank; 2) to return genomic research results to the participants of the cohort studies, which will lead to the implementation of personalized healthcare and medicine in the affected areas in the near future; and 3) to contribute the development of personalized healthcare and medicine worldwide. Through the activities of TMM, we will clarify how to approach prolonged healthcare problems in areas damaged by large-scale disasters and how useful genomic information is for disease prevention. PMID- 27374141 TI - Transmembrane protein 88 (TMEM88) promoter hypomethylation is associated with platinum resistance in ovarian cancer. AB - OBJECTIVES: Epigenetic alterations have been implicated in the development of platinum resistance in ovarian cancer (OC). In this study, we aimed to identify DNA methylation changes in platinum resistant tumors and their functional implications. METHODS: To identify DNA methylation alterations we used the Illumina 450k DNA methylation array and profiled platinum sensitive and resistant OC xenografts. Validation analyses employed RT-PCR and immunohistochemistry (IHC). RESULTS: Genome-wide DNA methylation analysis of OC xenografts identified 6 genes (SSH3, SLC12A4, TMEM88, PCDHGC3, DAXX, MEST) whose promoters were significantly hypomethylated in resistant compared to sensitive (control) xenografts (p<0.001). We confirmed that TMEM88 and DAXX mRNA expression levels were increased in platinum resistant compared to control xenografts, inversely correlated with promoter methylation levels. Furthermore treatment of OC cells with SGI-110 (guadecitabine), a DNA methyl transferase (DNMT) inhibitor, increased TMEM88 mRNA expression levels, supporting that TMEM88 is transcriptionally regulated by promoter methylation. TMEM88 was detectable by IHC in all histological types of ovarian tumors and its knock-down by using siRNA promoted OC cell proliferation and colony formation and re-sensitized cells to platinum. Furthermore, TMEM88 knock down induced upregulation of cyclin D1 and c Myc, known Wnt target genes, supporting that TMEM88 inhibits Wnt signaling. CONCLUSIONS: Overall, our results support that OC platinum resistance was correlated with TMEM88 overexpression regulated through decreased promoter methylation. Our data suggest that TMEM88 functions as an inhibitor of Wnt signaling, contributing to the development of platinum resistance. PMID- 27374142 TI - External validation of the IOTA ADNEX model performed by two independent gynecologic centers. AB - OBJECTIVES: The external, two-center validation of the IOTA ADNEX model for differential diagnosis of adnexal tumors. METHODS: A total of 204 patients with adnexal masses (134 benign and 70 malignant) treated at the Division of Gynecologic Surgery, Poznan University of Medical Sciences, Poland (Center I), and 123 patients (89 benign and 34 malignant) from the Department of Obstetrics and Gynecology, Clinica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain (Center II), were enrolled into the study. RESULTS: ADNEX achieved high accuracy in discriminating between malignant and benign ovarian tumors in both centers (79.9% and 81.3% in Centers I and II, respectively). Multiclass accuracy was substantially lower than in binary classification (malignant vs. benign): 64.2% and 74.0% in Centers I and II, respectively. Sensitivity and specificity for the diagnosis of specific tumor types in Center I were as follows: benign tumors - 72.4% and 94.3%; borderline tumors - 33.3% and 87.0%, stage I ovarian cancers - 00.0% and 91.8%; stage II-IV ovarian cancers - 68.2% and 83.1%; and metastatic tumors - 00.0% and 99.5%. Sensitivity and specificity in Center II were as follows: benign tumors - 75.3% and 97.1%; borderline tumors - 50.0% and 88.2%, stage I ovarian cancers - 40.0% and 97.5%; stage II-IV ovarian cancers - 95.0% and 88.3%; and metastatic tumors - 20.0% and 98.3%. CONCLUSIONS: ADNEX is characterized by very high accuracy in differentiating between malignant and benign adnexal tumors. However, prediction of ovarian tumor types could be more accurate. PMID- 27374143 TI - Last-Step Enzymatic [(18) F]-Fluorination of Cysteine-Tethered RGD Peptides Using Modified Barbas Linkers. AB - We report a last-step fluorinase-catalyzed [(18) F]-fluorination of a cysteine containing RGD peptide. The peptide was attached through sulfur to a modified and more hydrophilic variant of the recently disclosed Barbas linker which was itself linked to a chloroadenosine moiety via a PEGylated chain. The fluorinase was able to use this construct as a substrate for a transhalogenation reaction to generate [(18) F]-radiolabeled RGD peptides, which retained high affinity to cancer-cell relevant alphav beta3 integrins. PMID- 27374144 TI - Nursing knowledge: hints from the placebo effect. AB - Nursing knowledge stems from a dynamic interplay between population-based scientific knowledge (the general) and specific clinical cases (the particular). We compared the 'cascade model of knowledge translation', also known as 'classical biomedical model' in clinical practice (in which knowledge gained at population level may be applied directly to a specific clinical context), with an emergentist model of knowledge translation. The structure and dynamics of nursing knowledge are outlined, adopting the distinction between epistemic and non epistemic values. Then, a (moderately) emergentist approach to nursing knowledge is proposed, based on the assumption of a two-way flow from the general to the particular and vice versa. The case of the 'placebo effect' is analysed as an example of emergentist knowledge. The placebo effect is usually considered difficult to be explained within the classical biomedical model, and we underscore its importance in shaping nursing knowledge. In fact, nurses are primarily responsible for administering placebo in the clinical setting and have an essential role in promoting the placebo effect and reducing the nocebo effect. The beliefs responsible for the placebo effect are as follows: (1) interactive, because they depend on the relationship between patients and health care professionals; (2) situated, because they occur in a given clinical context related to certain rituals; and (3) grounded on higher order beliefs concerning what an individual thinks about the beliefs of others. It is essential to know the clinical context and to understand other people's beliefs to make sense of the placebo effect. The placebo effect only works when the (higher order) beliefs of doctors, nurses and patients interact in a given setting. Finally, we argue for a close relationship between placebo effect and nursing knowledge. PMID- 27374145 TI - A cost-effective high-throughput metabarcoding approach powerful enough to genotype ~44 000 year-old rodent remains from Northern Africa. AB - We present a cost-effective metabarcoding approach, aMPlex Torrent, which relies on an improved multiplex PCR adapted to highly degraded DNA, combining barcoding and next-generation sequencing to simultaneously analyse many heterogeneous samples. We demonstrate the strength of these improvements by generating a phylochronology through the genotyping of ancient rodent remains from a Moroccan cave whose stratigraphy covers the last 120 000 years. Rodents are important for epidemiology, agronomy and ecological investigations and can act as bioindicators for human- and/or climate-induced environmental changes. Efficient and reliable genotyping of ancient rodent remains has the potential to deliver valuable phylogenetic and paleoecological information. The analysis of multiple ancient skeletal remains of very small size with poor DNA preservation, however, requires a sensitive high-throughput method to generate sufficient data. We show this approach to be particularly adapted at accessing this otherwise difficult taxonomic and genetic resource. As a highly scalable, lower cost and less labour intensive alternative to targeted sequence capture approaches, we propose the aMPlex Torrent strategy to be a useful tool for the genetic analysis of multiple degraded samples in studies involving ecology, archaeology, conservation and evolutionary biology. PMID- 27374146 TI - Ultrasonographic imaging of the temporomandibular joint in healthy cattle and pathological findings in one clinical case. AB - AIMS: To describe the normal ultrasonographic appearance of the temporomandibular joint (TMJ) in cattle, and to describe the ultrasonographic pathology of the TMJ as assessed in one cow with TMJ disease. METHODS: The TMJ of 12 healthy Holstein Friesian cows were examined using a portable ultrasonographic unit with a 7.5 MHz linear probe and a 6.0 MHz convex probe. Each TMJ was scanned in a rostrolateral, lateral and caudolateral plane. In addition, the TMJ of one 2-year-old cow with clinical signs of food retention in the mouth, head tilt, swelling and pain in the right TMJ region and an infected horn fracture was examined ultrasonographically. RESULTS: The bone surfaces of the temporal process, the zygomatic process and the temporal bone, the larger muscles of the TMJ region, the superficial temporal vein, and the parotid salivary gland could be imaged in all normal healthy cattle. Using the linear probe, the joint capsule was visible in 17/24 (71%) cases in the caudolateral plane, but the articular disc could not be visualised. With the convex probe, the joint capsule could be imaged in all cases in the caudolateral plane, and the articular disc in 13/24 (54%) cases in the caudolateral plane. It was never possible to see the synovial pouch in healthy cattle using either probe. By contrast, in the cow diagnosed with septic arthritis of the right TMJ, a marked anechoic and heterogeneous hypoechoic effusion of the TMJ with distension of the joint capsule was visualised. CONCLUSIONS: The results of this descriptive study serve to provide a reference for ultrasonography of pathological conditions of the TMJ region in cattle. CLINICAL RELEVANCE: As many veterinarians are equipped with ultrasound machines with 5-8 MHz linear rectal probes, the authors recommend using these probes for further investigation of clinical cases with swelling of the TMJ region and/or masticatory problems of unclear origin to exclude or diagnose TMJ disorders. PMID- 27374147 TI - The fragmented self: imbalance between intrinsic and extrinsic self-networks in psychotic disorders. AB - Self-disturbances are among the core features of schizophrenia and related psychotic disorders. The basic structure of the self could depend on the balance between intrinsic and extrinsic self-processing. We discuss studies on self related processing in psychotic disorders that provide converging evidence for disrupted communication between neural networks subserving the so-called intrinsic self and extrinsic self. This disruption might be mainly caused by impaired integrity of key brain hubs. The intrinsic self has been associated with cortical midline structures involved in self-referential processing, autobiographical memory, and emotional evaluation. Additionally, we highlight central aspects of the extrinsic self in its interaction with the environment using sensorimotor networks, including self-experience in sensation and actions. A deficient relationship between these self-aspects because of disrupted between network interactions offers a framework to explain core clinical features of psychotic disorders. In particular, we show how relative isolation and reduced modularity of networks subserving intrinsic and extrinsic self-processing might trigger the emergence of hallucinations and delusions, and why patients with psychosis typically have difficulties with self-other relationships and do not recognise mental problems. PMID- 27374148 TI - Molecular characterization of the IgE-binding epitopes in the fast omega-gliadins of Triticeae in relation to wheat-dependent, exercise-induced anaphylaxis. AB - Fast omega-gliadins were minor components of wheat storage proteins but a major antigen triggering allergy to wheat. Sixty-six novel full-length fast omega gliadin genes with unique characteristics were cloned and sequenced from wheat and its relative species using a PCR-based strategy. Their coding regions ranged from 177bp to 987bp in length and encoded 4.28kDa to 37.56kDa proteins. On the base of first three deduced amino acids at the N-terminal, these genes could be classified into the six subclasses of SRL-, TRQ-, GRL-, NRL-, SRP- and SRM-type omega-gliadin genes. Compared by multiple alignments, these genes were significantly different from each other, due to the insertion or deletion at the repetitive domain. An analysis of the IgE-binding epitopes of the 66 deduced fast omega-gliadins demonstrated that they contained 0-24 IgE-binding epitopes. The phylogenetic tree demonstrated that the fast omega-gliadins and slow omega gliadins were separated into two groups and their divergence time was 21.64millionyears ago. Sequence data of the fast omega-gliadin genes assist in the study of the origins and evolutions of the different types of omega-gliadins while also providing a basis for the synthesis of monoclonal antibodies to detect wheat antigen content. PMID- 27374149 TI - Regulatory divergence of homeologous Atlantic salmon elovl5 genes following the salmonid-specific whole-genome duplication. AB - Fatty acyl elongase 5 (elovl5) is a critical enzyme in the vertebrate biosynthetic pathway which produces the physiologically essential long-chain polyunsaturated fatty acids (LC-PUFA), docosahexenoic acid (DHA), and eicosapentenoic acid (EPA) from 18 carbon fatty acids precursors. In contrast to most other vertebrates, Atlantic salmon possess two copies of elovl5 (elovl5a and elovl5b) as a result of a whole-genome duplication (WGD) which occurred at the base of the salmonid lineage. WGDs have had a major influence on vertebrate evolution, providing extra genetic material, enabling neofunctionalization to accelerate adaptation and speciation. However, little is known about the mechanisms by which such duplicated homeologous genes diverge. Here we show that homeologous Atlantic salmon elovl5a and elovl5b genes have been asymmetrically colonised by transposon-like elements. Identical locations and identities of insertions are also present in the rainbow trout duplicate elovl5 genes, but not in the nearest extant representative preduplicated teleost, the northern pike. Both elovl5 salmon duplicates possessed conserved regulatory elements that promoted Srebp1- and Srebp2-dependent transcription, and differences in the magnitude of Srebp response between promoters could be attributed to a tandem duplication of SRE and NF-Y cofactor binding sites in elovl5b. Furthermore, an insertion in the promoter region of elovl5a confers responsiveness to Lxr/Rxr transcriptional activation. Our results indicate that most, but not all, transposon mobilisation into elovl5 genes occurred after the split from the common ancestor of pike and salmon, but before more recent salmonid speciations, and that divergence of elovl5 regulatory regions have enabled neofuntionalization by promoting differential expression of these homeologous genes. PMID- 27374150 TI - Comparative analysis of gene expression profiles of hip articular cartilage between non-traumatic necrosis and osteoarthritis. AB - Hip cartilage destruction is consistently observed in the non-traumatic osteonecrosis of femoral head (NOFH) and accelerates its bone necrosis. The molecular mechanism underlying the cartilage damage of NOFH remains elusive. In this study, we conducted a systematically comparative study of gene expression profiles between NOFH and osteoarthritis (OA). Hip articular cartilage specimens were collected from 12 NOFH patients and 12 controls with traumatic femoral neck fracture for microarray (n=4) and quantitative real-time PCR validation experiments (n=8). Gene expression profiling of articular cartilage was performed using Agilent Human 4*44K Microarray chip. The accuracy of microarray experiment was further validated by qRT-PCR. Gene expression results of OA hip cartilage were derived from previously published study. Significance Analysis of Microarrays (SAM) software was applied for identifying differently expressed genes. Gene ontology (GO) and pathway enrichment analysis were conducted by Gene Set Enrichment Analysis software and DAVID tool, respectively. Totally, 27 differently expressed genes were identified for NOFH. Comparing the gene expression profiles of NOFH cartilage and OA cartilage detected 8 common differently expressed genes, including COL5A1, OGN, ANGPTL4, CRIP1, NFIL3, METRNL, ID2 and STEAP1. GO comparative analysis identified 10 common significant GO terms, mainly implicated in apoptosis and development process. Pathway comparative analysis observed that ECM-receptor interaction pathway and focal adhesion pathway were enriched in the differently expressed genes of both NOFH and hip OA. In conclusion, we identified a set of differently expressed genes, GO and pathways for NOFH articular destruction, some of which were also involved in the hip OA. Our study results may help to reveal the pathogenetic similarities and differences of cartilage damage of NOFH and hip OA. PMID- 27374151 TI - Complete nucleotide sequence of plasmid pNA6 reveals the high plasticity of IncU family plasmids. AB - Antibiotic resistance is a serious problem in health care and is of widespread public concern. Conjugative plasmids are the most important vectors in the dissemination of antibiotic resistance genes. In this study, we determined the complete sequence of plasmid pNA6, a plasmid which was isolated from the sediments of Haihe River. This plasmid confers reduced susceptibility to ampicillin, erythromycin and sulfamethoxazole. The complete sequence of plasmid pNA6 was 52,210bp in length with an average G+C content of 52.70%. Plasmid pNA6 belongs to the IncU group by sequence queries against the GenBank database. This plasmid has a typical IncU backbone and shows the highest similarities with plasmid RA3 and plasmid pFBAOT6. Plasmid pNA6 carries a class 1 integron consisting of aacA4, ereA and dfrA1 genes. Moreover, plasmid pNA6 also harbors a blaTEM-1-containing complex structure which inserted into the replication region and maintenance region. This insertion site has never been found on other IncU plasmids. The sequencing of plasmid pNA6 will add new sequence information to IncU family plasmids and enhance our understanding of the plasticity of IncU family plasmids. PMID- 27374152 TI - Diversity of cytosolic HSP70 Heat Shock Protein from decapods and their phylogenetic placement within Arthropoda. AB - The 70kDa heat shock proteins (HSP70) are considered the most conserved members of the HSP family. These proteins are primordial to the cell, because of their implications in many cellular pathways (e. g., development, immunity) and also because they minimize the effects of multiple stresses (e. g., temperature, pollutants, salinity, radiations). In the cytosol, two ubiquitous HSP70s with either a constitutive (HSC70) or an inducible (HSP70) expression pattern are found in all metazoan species, encoded by 5 or 6 genes (Drosophila melanogaster or yeast and human respectively). The cytosolic HSP70 protein family is considered a major actor in environmental adaptation, and widely used in ecology as an important biomarker of environmental stress. Nevertheless, the diversity of cytosolic HSP70 remains unclear amongst the Athropoda phylum, especially within decapods. Using 122 new and 311 available sequences, we carried out analyses of the overall cytosolic HSP70 diversity in arthropods (with a focus on decapods) and inferred molecular phylogenies. Overall structural and phylogenetic analyses showed a surprisingly high diversity in cytosolic HSP70 and revealed the existence of several unrecognised groups. All crustacean HSP70 sequences present signature motifs and molecular weights characteristic of non-organellar HSP70, with multiple specific substitutions in the protein sequence. The cytosolic HSP70 family in arthropods appears to be constituted of at least three distinct groups (annotated as A, B and C), which comprise several subdivisions, including both constitutive and inducible forms. Group A is constituted by several classes of Arthropods, while group B and C seem to be specific to Malacostraca and Hexapoda/Chelicerata, respectively. The HSP70 organization appeared much more complex than previously suggested, and far beyond a simple differentiation according to their expression pattern (HSC70 versus HSP70). This study proposes a new classification of cytosolic HSP70 and an evolutionary model of the distinct forms amongst the Arthropoda phylum. The observed differences between HSP70 groups will probably have to be linked to distinct interactions with co chaperones or other co-factors. PMID- 27374153 TI - Circulating miR-221-3p as a novel marker for early prediction of acute myocardial infarction. AB - Recent studies have reported circulating microRNAs (miRNAs) as novel biomarkers for cardiovascular diseases including acute myocardial infarction, heart failure, diabetes mellitus, stroke, and acute pulmonary embolism. The aims of this study were 1) to compare the plasma expression levels of miRNAs in patients with acute coronary syndrome (ACS) and control subjects and in ST-elevation myocardial infarction (STEMI) and non-STEMI 2) to evaluate miRNAs potential to be used as novel diagnostic biomarkers for ACS. Twenty seven consecutive patients, admitted to emergency department of a training and research hospital between January December 2013 with acute chest pain and/or dyspnea and diagnosed with ACS, and 16 non-ACS control subjects were included in this study. miRNA profiling was performed by using real time polymerase chain reaction. Functions of dysregulated miRNAs were evaluated by computerized-pathways analysis. miR-221-3p was one of the two most dysregulated miRNAs with a fold regulation of 3.89. It was significantly positively correlated with both Troponin and GRACE and Synthax Score. Moreover, miR221-3p was found to be significantly inversely correlated with left ventricular ejection fraction. miR-221-3p was the most prominent biomarker candidate with an area under curve (AUC) level of 0.881 (95% confidence interval: 0.774-0.987; p=0.002). The present study is the first to report an increased expression levels of miR-221-3p in AMI. Since miR-221-3p has a high discriminative value and significant relations with Troponin, GRACE and Synthax score and left ventricular systolic function, it may be a potential biomarker for early prediction of AMI. PMID- 27374154 TI - Functional, structural and epitopic prediction of hypothetical proteins of Mycobacterium tuberculosis H37Rv: An in silico approach for prioritizing the targets. AB - The global control of tuberculosis (TB) remains a great challenge from the standpoint of diagnosis, detection of drug resistance, and treatment. Major serodiagnostic limitations include low sensitivity and high cost in detecting TB. On the other hand, treatment measures are often hindered by low efficacies of commonly used drugs and resistance developed by the bacteria. Hence, there is a need to look into newer diagnostic and therapeutic targets. The proteome information available suggests that among the 3906 proteins in Mycobacterium tuberculosis H37Rv, about quarter remain classified as hypothetical uncharacterized set. This study involves a combination of a number of bioinformatics tools to analyze those hypothetical proteins (HPs). An entire set of 999 proteins was primarily screened for protein sequences having conserved domains with high confidence using a combination of the latest versions of protein family databases. Subsequently, 98 of such potential target proteins were extensively analyzed by means of physicochemical characteristics, protein-protein interaction, sub-cellular localization, structural similarity and functional classification. Next, we predicted antigenic proteins from the entire set and identified B and T cell epitopes of these proteins in M. tuberculosis H37Rv. We predicted the function of these HPs belong to various classes of proteins such as enzymes, transporters, receptors, structural proteins, transcription regulators and other proteins. However, the structural similarity prediction of the annotated proteins substantiated the functional classification of those proteins. Consequently, based on higher antigenicity score and sub-cellular localization, we choose two (NP_216420.1, NP_216903.1) of the antigenic proteins to exemplify B and T cell epitope prediction approach. Finally we found 15 epitopes those located partially or fully in the linear epitope region. We found 21 conformational epitopes by using Ellipro server as well. In silico methodology used in this study and the data thus generated for HPs of M. tuberculosis H37Rv may facilitate swift experimental identification of potential serodiagnostic and therapeutic targets for treatment and control. PMID- 27374155 TI - Identification of novel odorant binding protein genes and functional characterization of OBP8 in Chilo suppressalis (Walker). AB - At the peripheral level of the insect olfaction, odorant binding proteins (OBPs) are thought to bind and transport exogenous hydrophobic volatiles to the odorant receptors (ORs) located on the dendrite membrane of the olfactory neurons. In this study, cDNA sequences of 29 OBP genes from Chilo suppressalis, a notorious rice pest, were identified, with 15 of them being newly reported. The tissue and temporal expression patterns of these CsupOBPs were determined by RT-PCR, revealing that CsupOBP8, 10 and 24 were specifically expressed in the heads at larval stage and in antennae of both sexes at adult stage. In addition, CsupOBP 6, 9 and 18 were expressed in much higher levels in heads than abdomen at the larval stage, while CsupPBP4 and CsupOBP1, 3, 8, 11 and 24 were specifically expressed in antennae of both sexes at the adult stage. Such expression profile strongly suggests olfactory roles of these genes. Furthermore, the function of CsupOBP8 was chosen to be investigated by the competitive fluorescence binding assay. Results showed that CsupOBP8 displayed high binding affinities (Ki=4.9 15.0MUM) with plant volatile beta-ionone, nerolidol, farnesol and 2-hexanone, suggesting that CsupOBP8 plays olfactory roles through binding and transporting the plant volatiles. The study provides an important base for understanding the olfactory mechanisms in C. suppressalis. PMID- 27374156 TI - [Binge eating disorder: Links with personality and emotionality]. AB - OBJECTIVES: Our two objectives were: (1) to investigate the relationship between binge eating disorder, dimensions of personality (according to the Big Five model of Costa and McCrae) and those of emotionality in the "tripartite" model of emotions of Watson and Clark; (2) to evaluate the correspondence between the Binge Eating Scale (BES) and the Eating Disorder Inventory (EDI-2) scores. METHOD: Four self-administered questionnaires were completed on a shared doc website: the EDI-2, the BES, the BFI-Fr (Big Five Inventory-French version) and the EPN-31 (Positive and Negative Emotionality Scale). The analyses were conducted in a sample of 101 participants (36 men and 65 women), aged 20-59 years (mean age=35.28+/-9.76) from the general population. RESULTS: We found that 11% of the participants had moderate to severe binge eating disorder. Among them, nearly 4% were overweight and 4% were obese. The correlations analyses indicated that binge eating disorder was associated with two dimensions of personality, the neuroticism (P=0.001) and the consciousness (P=0.010), and with the emotions of joy (P=0.008), tenderness (P=0.036), fear (P=0.011), shame (P<0.001) and sadness (P=0.009). From a comparative perspective, participants with binge eating disorder get higher scores on EDI-2 subscales: search for thinness (P=0.001), bulimia (P<0.001), dissatisfaction with the body (P<0.001) and interceptive awareness (P<0.001). CONCLUSION: These results suggest that binge eating disorder is associated with negative affectivity both as a personality dimension and as an emotional feeling. The patterns of associations, observed with the EDI scale, seem to confirm the good convergent validity of the Binge Eating Scale. Thus, like other eating disorders, emotional functioning should be a prime target for prevention and treatment. PMID- 27374158 TI - Aberrant self-grooming as early marker of motor dysfunction in a rat model of Huntington's disease. AB - In the study of neurodegenerative diseases, rodent models provide experimentally accessible systems to study multiple pathogenetic aspects. The identification of early and robust behavioural changes is crucial to monitoring disease progression and testing potential therapeutic strategies in animals. Consistent experimental data support the translational value of rodent self-grooming as index of disturbed motor functions and perseverative behaviour patterns in different rodent models of brain disorders. Huntington's disease (HD) is a progressive neurodegenerative disorder, characterized by severe degeneration of basal ganglia, cognitive and psychiatric impairments and motor abnormalities. In the rat species, intrastriatal injection of the excitotoxin quinolinic acid (QA) mimics some of the neuroanatomical and behavioural changes found in HD, including the loss of GABAergic neurons and the appearance of motor and cognitive deficits. We show here that striatal damage induced by unilateral QA injection in dorsal striatum of rats triggers aberrant grooming behaviour as early as three weeks post-lesion in absence of other motor impairments: specifically, both quantitative (frequency and duration) and qualitative (the sequential pattern of movements) features of self-grooming behaviour were significantly altered in QA lesioned rats placed in either the elevated plus-maze and the open-field. The consistent abnormalities in self-grooming recorded in two different experimental contexts support the use of this behavioural marker in rodent models of striatal damage such as HD, to assess the potential effects of drug and cell replacement therapy in the early stage of disease. PMID- 27374157 TI - [Hazardous drinking in Parisian medical students]. AB - OBJECTIVES: Binge drinking is widespread in medical students but is poorly studied in France. The aim was to evaluate the number of binge drinking episodes and to better characterize them among a sample of French medical students. METHODS: We carried out a cross-sectional study at Paris VII's Faculty of Medicine. Through a brief self-questionnaire we focused on the prevalence rate of binge drinking in the past two weeks and examined the associations between hazardous drinking and the number of drinks consumed, demographic data (gender, age, familial status and student fraternity membership), clinical aspects (context, intended effects and adverse consequences), tobacco or illegal substances use, and eventual relationship with alcohol or tobacco use disorders. RESULTS: Among 302 medical students, 74.8% of them experienced at least one binge drinking episode in the last two weeks. There was no significant difference in demographic data. However, the association between binge drinking and to living alone was borderline significant (P=0.051). Students experienced on mean 2.4 (SD, 1.6) episodes in the last two weeks and their mean maximum number of drinks was equal to 10.3 (SD, 4.6). We observed a significant association between the number binge drinking episodes and the mean maximum consumption of alcohol drinks (P=0.004). The maximum quantity of alcohol drinks was significantly higher (P<0.001) in students who experienced two binge-drinking episodes (mean=11.23, SD=4.56), compared to those who experienced only one episode (mean=9.04, SD=3.96). Binge drinkers were more likely to consume alcohol at a party than at a friendly drink (P=0.029) and more frequently sought drunkenness (P<0.001) and to escape from daily concerns (P=0.004). They experienced more negative events like black-outs (P<0.001), aggressive behaviors (P=0.002), drunk driving (P=0.025), unsafe sexual relationships (P=0.010) and need of emergency responders (P=0.047). Binge drinkers were more likely to simultaneously consume tobacco (P<0.001) or illegal substances (P<0.001), and presented more alcohol use disorder (P<0.001) and tobacco-dependence (P=0.007). CONCLUSIONS: This first French study in 302 medical students has highlighted the extent of binge drinking in this specific population. The threshold of two binge-drinking episodes in two weeks may be useful to identify a distinctive pattern of consumption and set up adequate prevention actions. Finally binge drinking seemed to be close to an addictive process. Our findings support the need to develop targeted prevention programs in French medical students, which could be designed around several interventions in campuses and student parties. Cohort studies could be necessary to provide an epidemiological follow-up of the French medical student population, particularly about the risk of alcohol use disorder. PMID- 27374159 TI - Dopamine D1 receptor activity is involved in the increased anxiety levels observed in STZ-induced diabetes in rats. AB - Epidemiological surveys have indicated that anxiety disorders are more frequent in diabetic patients than in the general population. Similar results have been shown in animal studies using the streptozotocin (STZ)-induced diabetes model. The mechanisms underlying this relationship are not clearly understood, but it has been suggested that alterations in the dopaminergic neurotransmission, which plays an important role in the amygdaloid modulation of fear and anxiety, may be involved. The aim of this study was to ascertain whether or not the amygdaloid DA D1 receptors are involved in the increase of anxiety-like behavior observed in "diabetic" animals. Adult Wistar male rats were injected with STZ (50mg/kg, i.p.) in two consecutive days and subjected to the Shock-Probe Burying Test 10days after the beginning of treatment. STZ-treated rats showed a significant increase in immobility/freezing behavior whereas no effects were elicited in latency to bury, burying behavior itself and the number of shocks received during testing as compared with non-diabetic controls. These results suggest the triggering of a passive coping response in the STZ-treated rats. Interestingly, immobility/freezing behavior was reversed following the intra-amygdaloid dopamine D1 receptor blockade by the local microinfusion of SCH23390 (100ng/side). Autoradiographic experiments showed a selective increase of [(3)H]-SCH23390 binding in the ventral intercalated paracapsular islands of STZ-treated rats when compared to the non-treated control group. Our results suggest that a hyperdopaminergic state involving DA D1 receptors within the amygdala may have a role in the increase of anxiety observed in diabetic rats. PMID- 27374160 TI - D1- and D2-like dopamine receptors in the CA1 region of the hippocampus are involved in the acquisition and reinstatement of morphine-induced conditioned place preference. AB - The hippocampus plays a vital role in processing contextual memories and reward related learning tasks, such as conditioned place preference (CPP). Among the neurotransmitters in the hippocampus, dopamine is deeply involved in reward related processes. This study assessed the role of D1- and D2-like dopamine receptors within the CA1 region of the hippocampus in the acquisition and reinstatement of morphine-CPP. To investigate the role of D1 and D2 receptors in morphine acquisition, the animals received different doses of D1- and/or D2-like dopamine receptor antagonists (SCH23390 and sulpiride, respectively) into the CA1, 5min before the administration of morphine (5mg/kg, subcutaneously) during a 3-days conditioning phase. To evaluate the involvement of these receptors in morphine reinstatement, the animals received different doses of SCH23390 or sulpiride (after extinction period) 5min before the administration of a low dose of morphine (1mg/kg) in order to reinstate the extinguished morphine-CPP. Conditioning scores were recorded by Ethovision software. The results of this study showed that the administration of SCH23390 or sulpiride, significantly decreased the acquisition of morphine-CPP. Besides, the injection of these antagonists before the administration of a priming dose of morphine, following the extinction period, decreased the reinstatement of morphine-CPP in sacrificed rats. However, the effect of sulpiride on the acquisition and reinstatement of morphine-CPP was more significant than that of SCH23390. These findings suggested that D1- and D2-like dopamine receptors in the CA1 are involved in the acquisition and reinstatement of morphine-CPP, and antagonism of these receptors can reduce the rewarding properties of morphine. PMID- 27374161 TI - Facilitating effects of deep brain stimulation on feedback learning in Parkinson's disease. AB - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) provides an effective treatment for Parkinson's disease (PD) motor symptoms. However, findings of effects on cognitive function such as feedback learning remain controversial and rare. The aim of the present study was to gain a better understanding of cognitive alterations associated with STN-DBS. Therefore, we investigated effects of STN-DBS on active and observational feedback learning in PD. 18 PD patients with STN-DBS and 18 matched healthy controls completed active and observational feedback learning tasks. Patients were investigated ON and OFF STN-DBS. Tasks consisted of learning (with feedback) and test phases (without feedback). STN-DBS improved active learning during feedback trials and PD patients ON (but not OFF) STN-DBS showed comparable performance patterns as healthy controls. No STN-DBS effect was found when assessing performance during active test trials without feedback. In this case, however, STN-DBS effects were found to depend on symptom severity. While more impaired patients benefited from STN-DBS, stimulation had no facilitating effect on patients with less severe symptoms. Along similar lines, the severity of motor symptoms tended to be significantly correlated with differences in active test performance due to STN DBS. For observational feedback learning, there was a tendency for a positive STN DBS effect with patients reaching the performance level of healthy controls only ON STN-DBS. The present data suggest that STN-DBS facilitates active feedback learning in PD patients. Furthermore, they provide first evidence that STN-DBS might not only affect learning from own but also from observed actions and outcomes. PMID- 27374162 TI - The antidepressant-like effect of alarin is related to TrkB-mTOR signaling and synaptic plasticity. AB - Alarin is a newly derived neuropeptide from a splice variant of the galanin-like peptide gene. We previously showed that alarin has an antidepressant-like effect by increasing the activity of the extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) pathways, mediated by the tropomyosin-related kinase B receptor in the unpredictable chronic mild stress (UCMS) mouse model. Administration of rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, prevents the rapid antidepressant-like effect induced by ketamine in animal models, indicating a vital role of mTOR in depression pathophysiology. mTOR is a target of the ERK and AKT pathways that regulates the initiation of protein translation via its downstream components: ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1). Therefore, we hypothesized that the antidepressant-like effects of alarin were achieved by activating ERK/AKT pathways, increasing the activity of mTOR and its downstream signaling components that contribute to protein synthesis required for synaptic plasticity. Our results suggest that intracerebroventricular administration of alarin significantly ameliorates depression-like behaviors in the UCMS mouse model. Furthermore, alarin restored UCMS-induced reductions of p70S6K and post synaptic density 95 (PSD-95) mRNA levels, and of phospho-mTOR and phospho-4EBP1 in the prefrontal cortex, hippocampus, hypothalamus, and olfactory bulb. Additionally, alarin reversed the UCMS-induced downregulation of PSD-95 and synapsin I protein expression in these brain regions. Thus, the antidepressant like effects of alarin may be mediated by restoring decreased activity of the mTOR signaling pathway and expression of synaptic proteins. Our findings help advance the understanding of depression pathophysiology. PMID- 27374163 TI - The Effects of Prenatal Care Utilization on Maternal Health and Health Behaviors. AB - While many economic studies have explored the role of prenatal care in infant health production, the literature is sporadic on the effects of prenatal care on the mother. This research contributes to this understudied but important area using a unique large dataset of sibling newborns delivered by 0.17 million mothers. We apply within-mother estimators to find robust evidence that poor prenatal care utilization due to late onset of care, low frequency of care visits, or combinations of the two significantly increases the risks of maternal insufficient gestational weight gain, prenatal smoking, premature rupture of membranes, precipitous labor, no breastfeeding, postnatal underweight, and postpartum smoking. The magnitude of the estimates relative to the respective sample means of the outcome variables ranges from 3% to 33%. The results highlight the importance of receiving timely and sufficient prenatal care in improving maternal health and health behaviors during pregnancy as well as after childbirth. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27374164 TI - Long-Term Motor Deficits after Controlled Cortical Impact in Rats Can Be Detected by Fine Motor Skill Tests but Not by Automated Gait Analysis. AB - Animal models with constant, long-lasting motor deficits together with the right tests to assess behavioral abnormalities are needed to study the effectiveness of potential therapies to restore motor functions. In the current study, controlled cortical impact (CCI) was applied in rats to induce damage to the forelimb area of the motor cortex and the dorsal striatum. Motor behavior was assessed before and after CCI, using fine motor skill tests such as the adhesive removal test, the cylinder test, and the Montoya staircase test as well as the automated gait analysis system CatWalk XT over a 6 week period. CCI caused a variety of unilateral motor deficits, which were characterized in detail by using the selected fine motor skill tests. In striking contrast to previous studies on CCI in mice, neither forelimb impairments, nor general changes in gait, were detected with the CatWalk XT. These data suggest that the adhesive removal test, the cylinder test, and the Montoya staircase test are the methods of choice to detect long-term unilateral motor deficits in rats after CCI, whereas the use of automated gait analysis systems might not be suitable to measure these behavioral deviations. PMID- 27374166 TI - The Pauson-Khand reaction using alkynylboronic esters: solving a long-standing regioselectivity issue. AB - The first intermolecular Pauson-Khand reaction, conducted using internal alkynylboronic esters, allows the installation of the boronic ester moiety at the beta-position of the cyclopentenone with total regio- and stereoselectivity. PMID- 27374165 TI - Early hippocampal volume loss as a marker of eventual memory deficits caused by repeated stress. AB - Exposure to severe and prolonged stress has detrimental effects on the hippocampus. However, relatively little is known about the gradual changes in hippocampal structure, and its behavioral consequences, over the course of repeated stress. Behavioral analyses during 10 days of chronic stress pointed to a delayed decline in spatial memory, the full impact of which is evident only after the end of stress. In contrast, concurrent volumetric measurements in the same animals revealed significant reduction in hippocampal volumes in stressed animals relative to their unstressed counterparts, as early as the third day of stress. Notably, animals that were behaviorally the worst affected at the end of chronic stress suffered the most pronounced early loss in hippocampal volume. Together, these findings support the view that not only is smaller hippocampal volume linked to stress-induced memory deficits, but it may also act as an early risk factor for the eventual development of cognitive impairments seen in stress related psychiatric disorders. PMID- 27374168 TI - A proportion of primary squamous cell carcinomas of the parotid gland harbour high-risk human papillomavirus. AB - AIMS: In the current study, we aimed to examine primary parotid squamous cell carcinoma (ParSCC) for the presence of high-risk human papillomavirus (HR-HPV) and associated molecular alterations. METHODS AND RESULTS: Eight cases of ParSCC were retrieved after a detailed clinicopathological review to exclude the possibility of metastasis and/or extension from another primary site. HR-HPV status was determined on the basis of immunohistochemistry (IHC) for p16 expression and chromogenic in-situ hybridization (CISH) for HR-HPV. All cases were genotyped with a multiplexed mass spectrometry assay interrogating 91 hotspot mutations in eight cancer-related genes (EGFR, KRAS, NRAS, BRAF, PIK3CA, AKT1, MEK1 and ERBB2), and studied by fluorescence in-situ hybridization for PTEN copy number alteration. Three of eight cases (37.5%) were positive for the presence of HR-HPV by CISH and p16 IHC. One of three (33%) HR-HPV-positive cases harboured a PTEN hemizygous deletion, and one (33%) HR-HPV-positive case harboured a PIK3CA E545K somatic mutation. No alteration of the PTEN-PI3K pathway was detected in HR-HPV-negative tumours. Over a median follow-up period of 66.2 months, only the patient with the HR-HPV-positive PIK3CA-mutated tumour died of his disease, the remaining seven patients being disease-free. CONCLUSIONS: Given the established aetiological role of HR-HPV in other head and neck squamous cell carcinomas, it is likely that HR-HPV represents an oncogenic driver in the pathogenesis of more than one-third of ParSCCs. The presence of HR-HPV in ParSCC may be coupled with alterations in the PTEN-PI3K pathway. Further studies on HR HPV and the molecular characterization of a larger number of ParSCCs are needed to determine the clinical significance of these findings. PMID- 27374169 TI - The possible consequences for cognitive functions of external electric fields at power line frequency on hippocampal CA1 pyramidal neurons. AB - The possible effects on cognitive processes of external electric fields, such as those generated by power line pillars and household appliances are of increasing public concern. They are difficult to study experimentally, and the relatively scarce and contradictory evidence make it difficult to clearly assess these effects. In this study, we investigate how, why and to what extent external perturbations of the intrinsic neuronal activity, such as those that can be caused by generation, transmission and use of electrical energy can affect neuronal activity during cognitive processes. For this purpose, we used a morphologically and biophysically realistic three-dimensional model of CA1 pyramidal neurons. The simulation findings suggest that an electric field oscillating at power lines frequency, and environmentally measured strength, can significantly alter both the average firing rate and temporal spike distribution properties of a hippocampal CA1 pyramidal neuron. This effect strongly depends on the specific and instantaneous relative spatial location of the neuron with respect to the field, and on the synaptic input properties. The model makes experimentally testable predictions on the possible functional consequences for normal hippocampal functions such as object recognition and spatial navigation. The results suggest that, although EF effects on cognitive processes may be difficult to occur in everyday life, their functional consequences deserve some consideration, especially when they constitute a systematic presence in living environments. PMID- 27374170 TI - Spontaneous regression of a primary cutaneous diffuse large B-cell lymphoma, leg type. PMID- 27374167 TI - Nicotinic receptor activation contrasts pathophysiological bursting and neurodegeneration evoked by glutamate uptake block on rat hypoglossal motoneurons. AB - KEY POINTS: Impaired uptake of glutamate builds up the extracellular level of this excitatory transmitter to trigger rhythmic neuronal bursting and delayed cell death in the brainstem motor nucleus hypoglossus. This process is the expression of the excitotoxicity that underlies motoneuron degeneration in diseases such as amyotrophic lateral sclerosis affecting bulbar motoneurons. In a model of motoneuron excitotoxicity produced by pharmacological block of glutamate uptake in vitro, rhythmic bursting is suppressed by activation of neuronal nicotinic receptors with their conventional agonist nicotine. Emergence of bursting is facilitated by nicotinic receptor antagonists. Following excitotoxicity, nicotinic receptor activity decreases mitochondrial energy dysfunction, endoplasmic reticulum stress and production of toxic radicals. Globally, these phenomena synergize to provide motoneuron protection. Nicotinic receptors may represent a novel target to contrast pathological overactivity of brainstem motoneurons and therefore to prevent their metabolic distress and death. ABSTRACT: Excitotoxicity is thought to be one of the early processes in the onset of amyotrophic lateral sclerosis (ALS) because high levels of glutamate have been detected in the cerebrospinal fluid of such patients due to dysfunctional uptake of this transmitter that gradually damages brainstem and spinal motoneurons. To explore potential mechanisms to arrest ALS onset, we used an established in vitro model of rat brainstem slice preparation in which excitotoxicity is induced by the glutamate uptake blocker dl-threo-beta benzyloxyaspartate (TBOA). Because certain brain neurons may be neuroprotected via activation of nicotinic acetylcholine receptors (nAChRs) by nicotine, we investigated if nicotine could arrest excitotoxic damage to highly ALS-vulnerable hypoglossal motoneurons (HMs). On 50% of patch-clamped HMs, TBOA induced intense network bursts that were inhibited by 1-10 MUm nicotine, whereas nAChR antagonists facilitated burst emergence in non-burster cells. Furthermore, nicotine inhibited excitatory transmission and enhanced synaptic inhibition. Strong neuroprotection by nicotine prevented the HM loss observed after 4 h of TBOA exposure. This neuroprotective action was due to suppression of downstream effectors of neurotoxicity such as increased intracellular levels of reactive oxygen species, impaired energy metabolism and upregulated genes involved in endoplasmic reticulum (ER) stress. In addition, HMs surviving TBOA toxicity often expressed UDP-glucose glycoprotein glucosyltransferase, a key element in repair of misfolded proteins: this phenomenon was absent after nicotine application, indicative of ER stress prevention. Our results suggest nAChRs to be potential targets for inhibiting excitotoxic damage of motoneurons at an early stage of the neurodegenerative process. PMID- 27374171 TI - Clustered ventilation defects and bilinear respiratory reactance in asthma. AB - Imaging studies of asthmatics typically reveal clustered ventilation patterns, rather than homogeneous ventilation; furthermore, the variation of these clusters suggests that the causes are at least partially dynamic, rather than structural. Theoretical studies have indicated dynamic mechanisms by which homogeneous ventilation solutions lose stability and clustered solutions emerge. At the same time, it has been demonstrated experimentally that respiratory reactance characteristically has a bilinear relationship with lung volume, and that changes to this relationship are indicative of various aspects of disease progression and control. Moreover, the transition point in the bilinear reactance relationship is thought to relate to reopening/recruitment of airway units, and thus may be connected to the bifurcation via which clustered ventilation solutions emerge. In order to investigate this possibility we develop a new model, including both airway-airway coupling and airway-parenchymal coupling, which exhibits both clustered ventilation defects and also a bilinear reactance relationship. Studying this model reveals that (1) the reactance breakpoint is not coincident with the bifurcation; (2) numerous changes to underlying behaviour can alter the reactance breakpoint in ways which mimic the experimental data; and (3) the location of ventilation defects can be a combination of both structural and dynamic factors. PMID- 27374172 TI - Extended Cost-Effectiveness Analysis for Health Policy Assessment: A Tutorial. AB - Health policy instruments such as the public financing of health technologies (e.g., new drugs, vaccines) entail consequences in multiple domains. Fundamentally, public health policies aim at increasing the uptake of effective and efficient interventions and at subsequently leading to better health benefits (e.g., premature mortality and morbidity averted). In addition, public health policies can provide non-health benefits in addition to the sole well-being of populations and beyond the health sector. For instance, public policies such as social and health insurance programs can prevent illness-related impoverishment and procure financial risk protection. Furthermore, public policies can improve the distribution of health in the population and promote the equalization of health among individuals. Extended cost-effectiveness analysis was developed to address health policy assessment, specifically to evaluate the health and financial consequences of public policies in four domains: (1) the health gains; (2) the financial risk protection benefits; (3) the total costs to the policy makers; and (4) the distributional benefits. Here, we present a tutorial that describes both the intent of extended cost-effectiveness analysis and its keys to allow easy implementation for health policy assessment. PMID- 27374173 TI - miR-200b is a key regulator of tumor progression and metabolism targeting lactate dehydrogenase A in human malignant glioma. AB - Lactate dehydrogenase A (LDHA) is involved in various cancers. In this study, we investigated the expression and function of LDHA in glioma. We found that LDHA was up-regulated in glioma samples. Furthermore, we found that overexpression of LDHA promoted proliferation, invasion and glycolysis in glioma cells. Luciferase reporter assays confirmed that LDHA was a direct target of miR-200b. miR-200b was found to be down-regulated in glioma samples, which was inversely correlated with LDHA expression. Repression of LDHA by miR-200b suppressed the glycolysis, cell proliferation and invasion of glioma cells. These results provide evidence that miR-200b acts as a tumor suppressor in glioma through the inhibition of LDHA both in vitro and in vivo. Targeting LDHA through miR-200b could be a potential therapeutic strategy in glioma. PMID- 27374174 TI - MiRNA-200a expression is inverse correlation with hepatocyte growth factor expression in stromal fibroblasts and its high expression predicts a good prognosis in patients with non-small cell lung cancer. AB - Cancer-associated fibroblasts (CAFs) play an important role in favoring tumor progression. However, little is known concerning expression of miRNA-200a and its potential target gene hepatocyte growth factor (HGF) in CAFs. In the present study, we investigated expression levels and prognostic significance of miRNA 200a and HGF in stromal fibroblasts of non-small cell lung cancer (NSCLC), and evaluated the correlation between miRNA-200a and HGF. In situ hybridization and immunohistochemical staining were used to investigate expression levels of miRNA 200a and HGF in 134 formalin-fixed paraffin-embedded tumor specimens from clinical stage I -IIIA NSCLC, respectively. The results showed a significant inverse correlation existed between miRNA-200a and HGF expression level in stromal fibroblasts (chi2 = 21.778, p = 0.000). In vitro, the upregulation of miRNA-200a reduced expression of HGF protein in human CAFs. The 3-year overall survival (OS) rates with low and high miRNA-200a expression in stromal fibroblasts were 39.0% and 53.4%, respectively (chi2=4.25, p=0.039). The 3-year OS rates with low and high HGF expression in stromal fibroblasts were 60.3% and 31.8%, respectively (chi2=12.55, p=0.000). The multivariate analysis showed that clinical stage and HGF expression level in stromal fibroblasts were the independent predictive factors of OS. These results suggested that miRNA-200a expression was inverse correlation with HGF expression in stromal fibroblasts. High miRNA-200a and low HGF expression in stromal fibroblasts may predict a good prognosis in patients with NSCLC. PMID- 27374175 TI - Preoperative chemoradiotherapy creates an opportunity to perform sphincter preserving resection for low-lying locally advanced rectal cancer based on an oncologic outcome study. AB - Low-lying locally advanced rectal cancer (LARC) after preoperative chemoradiotherapy (CRT) can be surgically removed by either abdominperineal resection (APR) or sphincter preserving resection (SPR). This retrospective cohort study of 251 consecutive patients with low lying LARC who underwent CRT followed by radical surgery in a single institute, between March 2003 and November 2012, aimed to compare the oncological benefits between the two groups. 3-year disease free survival (DFS), overall survival (OS), cumulative incidence of recurrence and postoperative complications were compared between the two approaches. With median follow-up of 48.6 months, SPR group had higher 3-year DFS rate (86.4% vs 73.6%, P=0.023) and lower incidence of distant recurrence (12.0% vs 23.7%, P=0.026). The postoperative complications, incidence of local recurrence and the 3-year OS were comparable between the two groups. Pathologic T and N stage were the independent predictors for 3-year DFS (P=0.020 and P<0.001). In conclusion, our study suggest that low-lying LARC patients with a significant response to preoperative CRT can benefit from the advantage of SPR in preserving the anal sphincter function without compromising their oncologic outcome. PMID- 27374176 TI - A classical PKA inhibitor increases the oncolytic effect of M1 virus via activation of exchange protein directly activated by cAMP 1. AB - Oncolytic virotherapy is an emerging and promising treatment modality that uses replicating viruses as selective antitumor agents. Here, we report that a classical protein kinase A (PKA) inhibitor, H89, synergizes with oncolytic virus M1 in various cancer cells through activation of Epac1 (exchange protein directly activated by cAMP 1). H89 substantially increases viral replication in refractory cancer cells, leading to unresolvable Endoplasmic Reticulum stress, and cell apoptosis. Microarray analysis indicates that H89 blunts antiviral response in refractory cancer cells through retarding the nuclear translocation of NF-kappaB. Importantly, in vivo studies show significant antitumor effects during M1/H89 combination treatment. Overall, this study reveals a previously unappreciated role for H89 and demonstrates that activation of the Epac1 activity can improve the responsiveness of biotherapeutic agents for cancer. PMID- 27374177 TI - ART3 regulates triple-negative breast cancer cell function via activation of Akt and ERK pathways. AB - Triple-negative breast cancers (TNBCs) are defined by lack of expressions of estrogen, progesterone, and ERBB2 receptors. Because biology of TNBC is poorly understood, no targeted therapy has been developed for this breast cancer subtype and chemotherapy is its only systemic treatment modality. In this study, we firstly determined that the expression of human ecto-ADP-ribosyltransferase 3 (ART3) is significantly associated with the basal-like breast cancer subgroup, which is largely overlapped with TNBC, through analyzing published data sets. We also found that ART3 protein is significantly overexpressed in human TNBC tumors tissue and cell lines through using immunohistochemistry and immunoblotting. Overexpression of ART3 in MDA-MB-231 breast cancer cells increased cell proliferation, invasion, and survival in vitro and growth of xenograft tumors. Conversely, knockdown of ART3 in breast cancer cells inhibited cell proliferation and invasion. In addition, we showed that ART 3 overexpression activated AKT and ERK in vitro and in xenograft tumors. Together, our findings demonstrate that ART3 is a critical TNBC marker with functional significance. PMID- 27374178 TI - AHNAK enables mammary carcinoma cells to produce extracellular vesicles that increase neighboring fibroblast cell motility. AB - Extracellular vesicles play important roles in tumor development. Many components of these structures, including microvesicles and exosomes, have been defined. However, mechanisms by which extracellular vesicles affect tumor progression are not fully understood. Here, we investigated vesicular communication between mammary carcinoma cells and neighboring nontransformed mammary fibroblasts. Nonbiased proteomic analysis found that over 1% of the entire proteome is represented in these vesicles, with the neuroblast differentiation associated protein AHNAK and annexin A2 being the most abundant. In particular, AHNAK was found to be the most prominent component of these vesicles based on peptide number, and appeared necessary for their formation. In addition, we report here that carcinoma cells produce vesicles that promote the migration of recipient fibroblasts. These data suggest that AHNAK enables mammary carcinoma cells to produce and release extracellular vesicles that cause disruption of the stroma by surrounding fibroblasts. This paradigm reveals fundamental mechanisms by which vesicular communication between carcinoma cells and stromal cells can promote cancer progression in the tumor microenvironment. PMID- 27374179 TI - Cumulative defects in DNA repair pathways drive the PARP inhibitor response in high-grade serous epithelial ovarian cancer cell lines. AB - PARP inhibitors (PARPi), such as Olaparib, have shown promising results in high grade serous (HGS) epithelial ovarian cancer (EOC) treatment. PARPi sensitivity has been mainly associated with homologous recombination (HR) deficiency, but clinical trials have shown that predicting actual patient response is complex. Here, we investigated gene expression microarray, HR functionality and Olaparib sensitivity of 18 different HGS EOC cell lines and demonstrate that PARPi sensitivity is not only associated with HR defects. Gene target validation show that down regulation of genes in the nucleotide excision repair (NER) and mismatch repair (MMR) pathways (ERCC8 and MLH1, respectively) increases PARPi response. The highest sensitivity was observed when genes in both the HR and either NER or MMR pathways were concomitantly down regulated. Using clinical samples, patients with these concurrent down regulations could be identified. Based on these results, a novel model to predict PARPi sensitivity is herein proposed. This model implies that the extreme responders identified in clinical trials have deficiencies in HR and either NER or MMR. PMID- 27374181 TI - Increased expression of MUC3A is associated with poor prognosis in localized clear-cell renal cell carcinoma. AB - MUC3A is a membrane-associated mucin that recent evidence reveals the role of MUC3A in pathogenesis and progression of cancers. To evaluate the association between MUC3A expression with overall survival (OS) and recurrence-free survival (RFS) in patients with localized clear-cell renal cell carcinoma (ccRCC), we retrospectively detected MUC3A expression in samples of 384 postoperative localized ccRCC patients by immunohistochemistry. Median follow-up was 73 months (range: 42 - 74 mo). Overall, 41 patients died, 47 experienced recurrence. High MUC3A expression occurred in 45.8% of localized ccRCC cases, which was significantly associated with high pT-stage, high Fuhrman grade, high frequency of necrosis and LVI, and increased risk of recurrence and death (Logrank test P < 0.001 and P < 0.001, respectively). By multivariate analysis, MUC3A expression was confirmed as an adverse independent prognostic factor for OS and RFS. The prognostic accuracy of UISS, SSIGN, Leibovich models was significantly increased when MUC3A expression was integrated. Meanwhile, MUC3A was enrolled into a newly built nomogram with other factors selected by multivariate analysis. Calibration curves revealed optimal consistency between observations and prognosis. In conclusion, high MUC3A expression is an adverse prognostic biomarker for OS and RFS in postoperative localized ccRCC patients. PMID- 27374180 TI - EphrinA4 plays a critical role in alpha4 and alphaL mediated survival of human CLL cells during extravasation. AB - A role of endothelial cells in the survival of CLL cells during extravasation is presently unknown. Herein we show that CLL cells but not normal B cells can receive apoptotic signals through physical contact with TNF-alpha activated endothelium impairing survival in transendothelial migration (TEM) assays. In addition, the CLL cells of patients having lymphadenopathy (LApos) show a survival advantage during TEM that can be linked to increased expression of alpha4 and alphaL integrin chains. Within this context, ephrinA4 expressed on the surface of CLL cells sequestrates integrins and inactivates them resulting in reduced adhesion and inhibition of apoptotic/survival signals through them. In agreement, ephrinA4 silencing resulted in increased survival of CLL cells of LApos patients but not LA neg patients. Similarly was observed when a soluble ephrinA4 isoform was added to TEM assays strongly suggesting that accumulation of this isoform in the serum of LApos patients could contribute to CLL cells dissemination and survival in vivo. In supporting, CLL lymphadenopathies showed a preferential accumulation of apoptotic CLL cells around high endothelial venules lacking ephrinA4. Moreover, soluble ephrinA4 isolated from sera of patients increased the number and viability of CLL cells recovered from the lymph nodes of adoptively transferred mice. Finally, we present evidence suggesting that soluble ephrinA4 mediated survival during TEM could enhance a transcellular TEM route of the CLL cells. Together these findings point to an important role of ephrinA4 in the nodal dissemination of CLL cells governing extravasation and survival. PMID- 27374182 TI - Juvenile psoriasis: an epidemiological study of 69 cases. AB - BACKGROUND: Psoriasis is a common inflammatory skin disease that affects people of every age; prevalence in pediatric population is unknown because of the lack of studies. METHODS: We collected data about patients 0-18 years old coming to our center in the period from November 2010 to September 2012. RESULTS: We found 69 children (38 males, 31 females) affected by psoriasis, with a male-to-female ratio of 1.2 and a prevalence of 0.75%. Plaque psoriasis was the most common clinical manifestation (72.54%), followed by guttate psoriasis (13%). The most frequent comorbidities were overweight and obesity (26%). Most patients had a mild disease with PASI<10 (72.5%). the majority had no or limited effects on quality of life derived from psoriasis. The most frequent involved areas were the extremities (58%), followed by the scalp (45%). Eighty-four percent of children were treated with emollient agents, 50.7% with topical keratolytics, 24.6% with local steroids, vitamin D analogues or combination. CONCLUSIONS: The number of young patients affected by psoriasis confirmed rare literature reports on the topic. Most children showed mild form of disease. Nearly every child with mild psoriasis treated with topical therapy obtained good results. PMID- 27374184 TI - Neuroimaging in psychiatry: Current methods and future direction. PMID- 27374183 TI - Pancreatic cancer actionable genes in precision medicine and personalized surgery. AB - Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with an overall 5-year survival rate less than 5% due to the poor early diagnosis and lack of effective therapeutic options. The most effective therapy remains surgery, however post operative survival could be enhanced with effective adjuvant therapy. The massive information gained from Omics techniques on PDAC at the beginning of the 21st century is a remarkable accomplishment. However, the information gained from the omics data, including next generation sequencing data, has yet to successfully affect care of patients suffering with PDAC. Therefore, we propose the development of an actionable genomic platform that matches a patient's PDAC clinically actionable genes with potential targeted adjuvant therapies. Using this platform, PDX1 has been identified as a potential actionable gene for PDAC, therefore, RNAi therapy, gene therapy and small inhibitory drugs, all targeting PDX1, serve as potential targeted adjuvant therapies. Preclinical studies support the hypothesis that identification of PDAC actionable genes could permit translation of a patient's genomic information into precision targeted adjuvant therapy for PDAC. PMID- 27374185 TI - Cutting Edge Neuroimaging Research. PMID- 27374186 TI - Ondansetron Exposure Changes in a Pregnant Woman. AB - Pregnancy results in many physiologic changes that can alter the pharmacokinetic profiles of medications used during pregnancy. One of the primary factors leading to these pharmacokinetic changes is altered activity of drug-metabolizing enzymes. Ondansetron is a substrate of cytochrome P450 (CYP) 3A4 (primary metabolic pathway), 2D6, and 1A2, all of which are altered during pregnancy. We evaluated the pharmacokinetics of ondansetron at three different gestational time points in a 26-year-old, pregnant, Caucasian woman with normal liver and kidney function, who was maintained on ondansetron 8 mg administered orally 3 times/day throughout her pregnancy. Serial plasma samples were collected from the subject over one 8-hour dosing interval at 14, 24, and 35 weeks' gestation (representing early-, mid-, and late-pregnancy time points, respectively). Ondansetron plasma concentrations were determined using liquid chromatography-tandem mass spectrometry. Ondansetron area under the plasma concentration-time curve decreased progressively across gestation (634 ng hr/ml in early pregnancy, 553 ng hr/ml in mid-pregnancy, and 387 ng hr/ml in late pregnancy), with a corresponding increase in apparent oral clearance (12.6 L/hr in early-pregnancy, 14.5 L/hr in mid-pregnancy, and 20.7 L/hr in late-pregnancy). The decreased area under the plasma concentration-time curve and exposure to ondansetron across gestation is likely due to increased activity of CYP3A4 and CYP2D6 during pregnancy. We were not able to study this patient during the postpartum period; however, as with other CYP3A4 and CYP2D6 substrates, the apparent activities of these isoenzymes are likely return to baseline. To our knowledge, this is the first report to describe ondansetron pharmacokinetics across gestation. Additional pharmacokinetic and pharmacodynamic data are needed to confirm our results and to evaluate clinical impact; however, in the meantime, clinicians should be aware of these pharmacokinetic changes in ondansetron exposure during pregnancy. PMID- 27374187 TI - Development of a multifunctional envelope-type nano device and its application to nanomedicine. AB - Successful nanomedicines should be based on sound drug delivery systems (DDS) the permit intracellular trafficking as well as the biodistribution of cargos to be controlled. We have been developing new types of DDS that are multifunctional envelope-type nano devices referred to as MENDs. First, we will focus the in vivo delivery of siRNA to hepatocytes using a YSK-MEND which is composed of pH responsive cationic lipids. The YSK-MEND is capable of inducing efficient silencing activity in hepatocytes and can be used to cure mice that are infected with hepatitis C or B. The YSK-MEND can also be applied to cancer immunotherapy through the activation of immune cells by delivering different compounds such as cyclic-di-GMP, siRNA or alpha-galactosylceramide as a lipid antigen. The findings indicate that, as predicted, these compounds, when encapsulated in the YSK-MEND, can be delivered to the site of action and induced immune activation through different mechanisms. Finally, a MITO-Porter, a membrane fusion-based delivery system to mitochondria, is introduced as an organelle targeting DDS and a new strategy for cancer therapy is proposed by delivering gentamicin to mitochondria of cancer cells. These new technologies are expected to extend the therapeutic area of Nanomedicine by increasing the power of DDS, especially from the view point of controlled intracellular trafficking. PMID- 27374188 TI - Soluble expression, purification and functional characterisation of carboxypeptidase G2 and its individual domains. AB - Due to its applications in the treatment of cancer and autoimmune diseases, the 42 kDa zinc-dependent metalloenzyme carboxypeptidase G2 (CPG2) is of great therapeutic interest. An X-ray crystal structure of unliganded CPG2 reported in 1997 revealed the domain architecture and informed early rational drug design efforts, however further efforts at co-crystallization of CPG2 with ligands, substrates or inhibitors have not been reported. Thus key features of CPG2 such as the location of the active site, the presence of additional ligand-binding sites, stability, oligomeric state, and the molecular basis of activity remain largely unknown, with the current working understanding of CPG2 activity based primarily on computational modelling. To facilitate renewed efforts in CPG2 structural biology, we report the first high-yield (250 mg L(-1)) recombinant expression (and purification) of soluble and active CPG2 using the Escherichia coli expression system. We used this protocol to produce full-length enzyme, as well as protein fragments corresponding to the individual catalytic and dimerization domains, and the activity and stability of each construct was characterised. We adapted our protocol to allow for uniform incorporation of NMR labels ((13)C, (15)N and (2)H) and present preliminary solution-state NMR spectra of high quality. Taken together, our results offer a route for production and solution-state characterization that supports renewed effort in CPG2 structural biology as well as design of significantly truncated CPG2 proteins, which retain activity while yielding (potentially) improved immunogenicity. PMID- 27374189 TI - EGCG, a green tea catechin, attenuates the progression of heart failure induced by the heart/muscle-specific deletion of MnSOD in mice. AB - BACKGROUND: Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme affected in heart/muscle-specific MnSOD-deficient mice (H/M-SOD2-/-), which develop progressive congestive heart failure and exhibit pathology typical of dilated cardiomyopathy. METHODS: In this study we investigated the beneficial effects of epigallocatechin gallate (EGCG) on the cardiac remodeling and telomere biology in H/M-SOD2-/- mice. H/M-SOD2-/- mice were divided into three groups: those receiving normal drinking water (KO), a low dose of EGCG (L: 10mg/L), and a high dose of EGCG (H: 100mg/L) beginning at eight weeks of age and lasting for eight weeks. RESULTS: The mice in the KO group exhibited significantly dilated cardiac remodeling with reduced contractility, which was prevented by the administration of EGCG. Although the mortality of KO mice was about 50% at 16 weeks of age, the mice that received EGCG had a high survival rate. The cardiac dilatation with reduced cardiac contraction in KO mice was prevented by EGCG treatment. The levels of myocardial oxidative stress and free fatty acids were lower in the group treated with EGCG compared with the KO group. The increased expression of nitric oxide synthase 2, nitrotyrosine, fatty acid synthase, Toll like receptor 4, and Sirt1 in the KO mice were prevented by EGCG treatment. The shortening of the telomere length, decreased telomerase activity in KO mice were also prevented by EGCG. CONCLUSIONS: H/M-SOD2-/- mice receiving EGCG have a lower mortality rate and exhibit less inflammation and a better preserved cardiac function and telomere biology. PMID- 27374190 TI - Inhibition of Regulatory-Associated Protein of Mechanistic Target of Rapamycin Prevents Hyperoxia-Induced Lung Injury by Enhancing Autophagy and Reducing Apoptosis in Neonatal Mice. AB - Administration of supplemental oxygen remains a critical clinical intervention for survival of preterm infants with respiratory failure. However, prolonged exposure to hyperoxia can augment pulmonary damage, resulting in developmental lung diseases embodied as hyperoxia-induced acute lung injury and bronchopulmonary dysplasia (BPD). We sought to investigate the role of autophagy in hyperoxia-induced apoptotic cell death in developing lungs. We identified increased autophagy signaling in hyperoxia-exposed mouse lung epithelial-12 cells, freshly isolated fetal type II alveolar epithelial cells, lungs of newborn wild-type mice, and human newborns with respiratory distress syndrome and evolving and established BPD. We found that hyperoxia exposure induces autophagy in a Trp53-dependent manner in mouse lung epithelial-12 cells and in neonatal mouse lungs. Using pharmacological inhibitors and gene silencing techniques, we found that the activation of autophagy, upon hyperoxia exposure, demonstrated a protective role with an antiapoptotic response. Specifically, inhibiting regulatory-associated protein of mechanistic target of rapamycin (RPTOR) in hyperoxia settings, as evidenced by wild-type mice treated with torin2 or mice administered (Rptor) silencing RNA via intranasal delivery or Rptor+/-, limited lung injury by increased autophagy, decreased apoptosis, improved lung architecture, and increased survival. Furthermore, we identified increased protein expression of phospho-beclin1, light chain-3-II and lysosomal-associated membrane protein 1, suggesting altered autophagic flux in the lungs of human neonates with established BPD. Collectively, our study unveils a novel demonstration of enhancing autophagy and antiapoptotic effects, specifically through the inhibition of RPTOR as a potentially useful therapeutic target for the treatment of hyperoxia-induced acute lung injury and BPD in developing lungs. PMID- 27374191 TI - Interobserver variability in radiation therapy plan output: Results of a single institution study. AB - PURPOSE: We investigated the sources of variability in radiation therapy treatment plan output between planners within a single institution. METHODS AND MATERIALS: Forty treatment planners across 5 campuses of an institution created a plan on the same thoracic esophagus patient computed tomography scan and structure set. Plans were scored and ranked based on the planner's adherence to an ordered list of target dose coverage and normal tissue evaluation criteria. A runs test was used to identify whether any of the studied planner qualities influenced the ranking. Spearman rank correlation was used to investigate whether plan score correlated with years of experience or planned monitor units. RESULTS: The distribution of scores, ranging from 80.24 to 135.89, was negatively skewed (mean, 128.7; median, 131.5). No statistically significant relationship between plan score and campus (P = .193), job title (P = .174), previous outside experience (P = .611), or number of gantry angles (P = .156) was discovered. No statistical correlation between plan score and monitor unit or years of experience was found. CONCLUSIONS: Despite clear and established critical organ dose criteria and well-documented planning guidelines, planning variation still occurs, even among members of the same institution. Because plan consistency does not seem to significantly correlate with experience, career path, or campus, investigation into alternate methods beyond additional education and training to reduce this variation, such as knowledge-based planning or advanced optimization techniques, is necessary. PMID- 27374192 TI - Optimal bladder volume at treatment planning for prostate cancer patients receiving volumetric modulated arc therapy. AB - PURPOSE: To investigate optimal bladder volumes at treatment planning (TP) in prostate cancer patients who undergo volumetric modulated arc therapy (VMAT). METHODS AND MATERIALS: To determine the minimum value, 122 patients were classified into 6 groups according to the bladder volume at TP: <100 mL (group 1), 100-149 mL (group 2), 150-199 mL (group 3), 200-249 mL (group 4), 250-299 mL (group 5), and >=300 mL (group 6). Bladder volumes receiving more than 70 Gy (V70Gy) and V50Gy were calculated in each subgroup and compared with the bladder dose-volume constraints specified in our institution. To determine the maximum value, 64 patients who underwent uniform nursing interventions were classified into the same 6 groups. Bladder volumes on cone beam computed tomography (CBCT) images were measured once weekly during treatment, for a total of 8 measurements. Relative bladder volumes (bladder volume on CBCT image [mL]/bladder volume at TP [mL] * 100%) were evaluated in each of the 6 subgroups. RESULTS: The upper bounds of the 95% confidence intervals of the mean V70Gy and V50Gy values in group 1 exceeded the dose constraints at our institution. The mean relative bladder volumes were 104%, 91%, 77%, 81%, 63%, and 59% in groups 1, 2, 3, 4, 5, and 6, respectively. The institutional criterion of 70% for the mean relative bladder volume was achieved in groups 1-4, but it could not be achieved in groups 5-6. Therefore, the patients in groups 2-4 met both institutional dose constraints for the bladder at TP and the institutional criterion for the mean relative bladder volume during treatment. CONCLUSIONS: The optimal bladder volumes at TP were between 100 and 250 mL in this setting. Nursing intervention needs to be implemented before treatment planning to ensure that patients achieve the optimal bladder volume range. PMID- 27374193 TI - Neutral Diboron Analogues of Archetypal Aromatic Species by Spontaneous Cycloaddition. AB - Among the numerous routes organic chemists have developed to synthesize benzene derivatives and heteroaromatic compounds, transition-metal-catalyzed cycloaddition reactions are the most elegant. In contrast, cycloaddition reactions of heavier alkene and alkyne analogues, though limited in scope, proceed uncatalyzed. In this work we present the first spontaneous cycloaddition reactions of lighter alkene and alkyne analogues. Selective addition of unactivated alkynes to boron-boron multiple bonds under ambient conditions yielded diborocarbon equivalents of simple aromatic hydrocarbons, including the first neutral 6 pi-aromatic diborabenzene compound, a 2 pi-aromatic triplet biradical 1,3-diborete, and a phosphine-stabilized 2 pi-homoaromatic 1,3-dihydro 1,3-diborete. DFT calculations suggest that all three compounds are aromatic and show frontier molecular orbitals matching those of the related aromatic hydrocarbons, C6 H6 and C4 H4 (2+) , and homoaromatic C4 H5 (+) . PMID- 27374194 TI - Ethyl oleate-containing nanostructured lipid carriers improve oral bioavailability of trans-ferulic acid ascompared with conventional solid lipid nanoparticles. AB - trans-Ferulic acid (TFA) has antioxidative, anti-inflammatory, and cardioprotective effects, but its poor solubility in water results in unsatisfactory oral bioavailability when administered conventionally at a standard dosage. However, the limited bioavailability of TFA can be overcome by delivering it in nanostructured lipid carriers (NLCs). In this study, a microemulsion (ME)-based method was used to prepare NLCs with ethyl oleate as the liquid lipid component and glyceryl behenate as the solid lipid component. These NLCs and solid lipid nanoparticles (SLNs) were then used as vehicles for TFA. Their entrapment efficiencies (EE), stability during storage, in vitro release profiles, and in vivo pharmacokinetics were compared. The NLC formulation afforded a drug entrapment efficiency that was significantly greater than that of the SLN formulation, which was made using a single solid lipid. Furthermore, the TFA that was dispersed in the disordered binary lipid matrix of the NLC formulation was more stable than that in the SLN formulation, and thus showed less expulsion from the vehicle during storage. In in vivo pharmacokinetic studies, the NLC TFA formulation yielded a greater Cmax and AUC than that produced by the SLN formulation and an aqueous TFA suspension. This showed that the oral bioavailability of TFA was markedly improved by packaging in NLCs. NLCs are thus a promising vehicle for oral TFA administration, with significant advantages over SLNs. PMID- 27374195 TI - Biotin-targeted Pluronic((r)) P123/F127 mixed micelles delivering niclosamide: A repositioning strategy to treat drug-resistant lung cancer cells. AB - With the aim to develop alternative therapeutic tools for the treatment of resistant cancers, here we propose targeted Pluronic((r)) P123/F127 mixed micelles (PMM) delivering niclosamide (NCL) as a repositioning strategy to treat multidrug resistant non-small lung cancer cell lines. To build multifunctional PMM for targeting and imaging, Pluronic((r)) F127 was conjugated with biotin, while Pluronic((r)) P123 was fluorescently tagged with rhodamine B, in both cases at one of the two hydroxyl end groups. This design intended to avoid any interference of rhodamine B on biotin exposition on PMM surface, which is a key fundamental for cell trafficking studies. Biotin-decorated PMM were internalized more efficiently than non-targeted PMM in A549 lung cancer cells, while very low internalization was found in NHI3T3 normal fibroblasts. Biotin-decorated PMM entrapped NCL with good efficiency, displayed sustained drug release in protein rich media and improved cytotoxicity in A549 cells as compared to free NCL (P<0.01). To go in depth into the actual therapeutic potential of NCL-loaded PMM, a cisplatin-resistant A549 lung cancer cell line (CPr-A549) was developed and its multidrug resistance tested against common chemotherapeutics. Free NCL was able to overcome chemoresistance showing cytotoxic effects in this cell line ascribable to nucleolar stress, which was associated to a significant increase of the ribosomal protein rpL3 and consequent up-regulation of p21. It is noteworthy that biotin-decorated PMM carrying NCL at low doses demonstrated a significantly higher cytotoxicity than free NCL in CPr-A549. These results point at NCL-based regimen with targeted PMM as a possible second-line chemotherapy for lung cancer showing cisplatin or multidrug resistance. PMID- 27374196 TI - Tunable delivery of niflumic acid from resorbable embolization microspheres for uterine fibroid embolization. AB - Uterine arteries embolization (UAE) is a recent technique that aims, by means of particles injected percutaneously, to stifle fibroids (leiomyomas). This treatment is non-invasive, compared with uterine ablation, but generates pelvic pain for a few days. A strategy to reduce the post-embolization pain would be to use calibrated embolization microspheres preloaded with a non-steroidal inflammatory drug (NSAID). In this study, we first compared four drugs, all active at low concentration on cyclooxygenase-2, i.e. ketoprofen, sodium diclofenac, flurbiprofen and niflumic acid (NFA), for their capacity to be loaded on resorbable embolization microspheres (REM) 500-700MUm. NFA had the highest capacity of loading (5mg/mL) on resorbable microspheres. Then, we evaluated in vitro the NFA release profiles from REM having various degradation times of one, two or five days. NFA release was biphasic, with an initial burst (about 60% of the loading) followed by a sustained release that correlated significantly to REM's hydrolysis (rho=0.761, p<0.0001). For each group of beads, the size distribution was not modified by the loading of NFA and their delivery through microcatheter was not impaired by the drug. NFA eluted from REM inhibited the synthesis of prostaglandin E2 from rabbit uterus explants. In summary, NFA is loadable on REM in significant amount and its delivery can be tuned according to the degradation rate of REM to provide an antalgic effect for a few days after UAE. PMID- 27374197 TI - Hierarchical mesoporous silica nanoparticles for tailorable drug release. AB - In order to modulate the drug release profiles, the hierarchical mesoporous silica nanoparticles (HMSNs) are fabricated by a two-step synthetic process. The HMSNs exhibit uniform spherical morphology with nanoscaled size, well mono dispersed size distribution, and smooth surface. Because of the hierarchical pore structures with different mesoporous sizes and morphologies (partial open and partial blocked pores), the HMSNs can release the loaded drug in a controlled manner. The hierarchical mesoporous structures directed drug release profiles suggest a feasible strategy to tailor drug release behaviors. Meanwhile, the HMSNs exhibit good biocompatibility. Therefore, the HMSNs having tailorable drug release capacity would be a potential candidate to improve their therapeutic efficiency for drug delivery systems. PMID- 27374198 TI - Brain tumor-targeted therapy by systemic delivery of siRNA with Transferrin receptor-mediated core-shell nanoparticles. AB - Treatment of brain tumor remains a great challenge worldwide. Development of a stable, safe, and effective siRNA delivery system which is able to cross the impermeable blood-brain barrier (BBB) and target glioma cells is necessary. This study aims to investigate the therapeutic effects of intravenous administration of T7 peptide modified core-shell nanoparticles (named T7-LPC/siRNA NPs) on brain tumors. Layer-by-layer assembling of protamine/chondroitin sulfate/siRNA/cationic liposomes followed by T7 peptide modification has been carried out in order to obtain a targeted siRNA delivery system. In vitro cellular uptake experiments demonstrated a higher intracellular fluorescence intensity of siRNA in brain microvascular endothelial cells (BMVECs) and U87 glioma cells when treated with T7-LPC/siRNA NPs compared with PEG-LPC/siRNA NPs. In the co-culture model of BMVECs and U87 cells, a significant down-regulation of EGFR protein expression occurred in the U87 glioma cells after treatment with the T7-LPC/siEGFR NPs. Moreover, the T7-LPC/siRNA NPs had an advantage in penetrating into a deep region of the tumor spheroid compared with PEG-LPC/siRNA NPs. In vivo imaging revealed that T7-LPC/siRNA NPs accumulated more specifically in brain tumor tissues than the non-targeted NPs. Also, in vivo tumor therapy experiments demonstrated that the longest survival period along with the greatest downregulation of EGFR expression in tumor tissues was observed in mice with an intracranial U87 glioma treated with T7-LPC/siEGFR NPs compared with mice receiving other formulations. Therefore, we believe that these transferrin receptor-mediated core-shell nanoparticles are an important potential siRNA delivery system for brain tumor targeted therapy. PMID- 27374199 TI - Structure, activity and uptake mechanism of siRNA-lipid nanoparticles with an asymmetric ionizable lipid. AB - Lipid nanoparticles (LNPs) represent the most advanced platform for the systemic delivery of siRNA. We have previously reported the discovery of novel ionizable lipids with asymmetric lipid tails, enabling potent gene-silencing activity in hepatocytes in vivo; however, the structure and delivery mechanism had not been elucidated. Here, we report the structure, activity and uptake mechanism of LNPs with an asymmetric ionizable lipid. Zeta potential and hemolytic activity of LNPs showed that LNPs were neutral at the pH of the blood compartment but become increasingly charged and fusogenic in the acidic endosomal compartment. (31)P NMR experiments indicated that the siRNA was less mobile inside particles, presumably because of an electrostatic interaction with an ionizable lipid. The role of Apolipoprotein E (apoE) was studied using recombinant human apoE both in vitro and in vivo. A comparative study in wild-type and apoE-deficient mice revealed that apoE significantly influenced the in vivo biodistribution of LNPs and enhanced the cellular uptake. Pretreatment of mice with siRNA targeting low density lipoprotein receptor (LDLR) impaired gene-silencing of the following siRNA treatment, demonstrating that in vivo activity of LNPs is dependent on LDLR. Our studies on the detailed mechanism should lead to the creation of more sophisticated LNP-based RNAi therapeutics. PMID- 27374202 TI - Application of water-insoluble polymers to orally disintegrating tablets treated by high-pressure carbon dioxide gas. AB - The phase transition of pharmaceutical excipients that can be induced by humidifying or heating is well-known to increase the hardness of orally disintegrating tablets (ODTs). However, these conditions are not applicable to drug substances that are chemically unstable against such stressors. Here, we describe a system which enhances the hardness of tablets containing water insoluble polymers by using high-pressure carbon dioxide (CO2). On screening of 26 polymeric excipients, aminoalkyl methacrylate copolymer E (AMCE) markedly increased tablet hardness (+155N) when maintained in a high-pressure CO2 environment. ODTs containing 10% AMCE were prepared and treatment with 4.0MPa CO2 gas at 25 degrees C for 10min increased the hardness to +30N, whose level corresponded to heating at 70 degrees C for 720min. In addition, we confirmed the effects of CO2 pressure, temperature, treatment time, and AMCE content on the physical properties of ODTs. Optimal pressure of CO2 gas was considered to be approximately 3.5MPa for an AMCE formula, as excessive pressure delayed the disintegration of ODTs. Combination of high-pressure CO2 gas and AMCE is a prospective approach for increasing the tablet hardness for ODTs, and can be conducted without additional heat or moisture stress using a simple apparatus. PMID- 27374200 TI - Preparation and characterization of Chinese yam polysaccharide PLGA nanoparticles and their immunological activity. AB - This paper first provides that Chinese yam polysaccharide (CYP) is encapsulated by PLGA using a double emulsion solvent evaporation method and aims to screen the optimal preparation of CYP-PLGA nanoparticles (CYPP) using response surface methodology (RSM). The volume ratio of the internal water phase to the organic phase (W1:O), the volume ratio of the primary emulsion to the external water phase (PE:W2) and the concentration of Poloxamer 188 (F68) are deemed key variables for the encapsulation efficiency of CYPP. The results demonstrated that the data were accurately fitted into the RSM model. According to the RSM, the optimal scheme was a volume ratio of W1:O of 1:9, a volume ratio of PE: W2 of 1:10 and a concentration of F68 (W/V) of 0.7%. TEM and SEM images demonstrated that the nanoparticles had a spherical shape and smooth surface. The CYP and CYPP in vitro release studies demonstrated that the CYPP showed a release rate 53.41% lower than the release rate of CYP after 48h. The result of pro-proliferation and flow cytometry emerged that the CYPP were more effective compared with the free CYP and blank PLGA nanoparticles in promoting lymphocyte proliferation and triggering the transformation of T lymphocytes into Th cells. PMID- 27374201 TI - On the importance of Bloom number of gelatin to the development of biodegradable in situ gelling copolymers for intracameral drug delivery. AB - To overcome the drawbacks associated with conventional antiglaucoma eye drops, this work demonstrated the feasibility of an effective alternative strategy to administer pilocarpine directly via intracameral injections of drug-containing biodegradable in situ gelling GN copolymers composed of gelatin and poly(N isopropylacrylamide). Specifically, this study aims to understand the importance of Bloom number of gelatin, a physicochemical parameter, to the development of GN carriers for intracameral drug delivery in glaucoma therapy. Our results showed that both imino acid and triple-helix contents increased with increasing Bloom index from 75-100 to 300. The drug encapsulation efficiency in response to temperature-triggered phase transition in GN copolymers was affected by the Bloom index of gelatin. In addition, the differences in protein secondary structure significantly influenced the degradation rates of GN carriers, which were highly correlated with drug release profiles. The increase in released pilocarpine concentration led to a high intracellular calcium level in rabbit ciliary smooth muscle cell cultures, indicating a beneficial pharmacological response to a drug. Irrespective of Bloom number of gelatin, all carrier materials exhibited excellent in vitro and in vivo biocompatibility with corneal endothelium. In a glaucomatous rabbit model, intracameral injections of pilocarpine-containing GN synthesized from gelatins with various Bloom numbers had different abilities to improve ocular hypertension and induce pupillary constriction, indicating distinct antiglaucoma efficacies due to in vivo drug release. It is concluded that the effects on pharmacological treatment using GN carriers for intracameral pilocarpine administration demonstrate a strong dependence on the Bloom number of gelatin. PMID- 27374203 TI - The use of rheology to elucidate the granulation mechanisms of a miscible and immiscible system during continuous twin-screw melt granulation. AB - Twin-screw hot melt granulation (TS HMG) is a valuable, but still unexplored alternative to granulate temperature and moisture sensitive drugs in a continuous way. Recently, the material behavior of an immiscible drug-binder blend during TS HMG was unraveled by using a rheometer and differential scanning calorimetry (DSC). Additionally, vibrational spectroscopic techniques proved the link between TS HMG and rheology since equal interactions at molecular level did occur in both processes. This allowed to use a rheometer to gain knowledge of the material behavior during hot melt processing of an immiscible drug-binder blend. However, miscibility of a drug-binder formulation and drug-binder interactions appear to influence the rheological properties and, hence conceivably also the granulation mechanism. The aim of this research was to examine if the TS HMG process of a miscible formulation system is comparable with the mechanism of an immiscible system and to evaluate whether rheology still serves as a useful tool to understand and optimize the hot melt granulation (HMG) process. The executed research (thermal analysis, rheological parameters and spectroscopic data) demonstrated the occurrence of a high and broad tan(delta) curve without a loss peak during the rheological temperature ramp which implies a higher material deformability without movement of the softened single polymer chains. Spectroscopic analysis revealed drug-polymer interactions which constrain the polymer to flow independently. As a result, the binder distribution step, which generally follows the immersion step, was hindered. This insight assisted the understanding of the granule properties. Inhomogeneous granules were produced due to large initial nuclei or adhesion of multiple smaller nuclei. Consequently, a higher granulation temperature was required in order to get the binder more homogeneously distributed within the granules. PMID- 27374204 TI - Fabrication of nanocomposite particles using a two-solution mixing-type spray nozzle for use in an inhaled curcumin formulation. AB - A unique two-solution mixing-type spray nozzle is useful for producing nanocomposite particles (microparticles containing drug nanoparticles) in one step. The nanocomposite particles can prevent nanoparticle aggregation. Curcumin has many reported pharmacological effects. Curcumin was entrapped in mannitol microparticles using a spray dryer coupled with a two-solution mixing-type spray nozzle to prepare "curcumin nanocomposite particles" and the application of these particles for inhalation formulations was investigated. Spray drying conditions (flow rate, concentration and inlet temperature) affected the size of both the resulting curcumin nanocomposite particles and the curcumin nanoparticles in the nanocomposite particles. The aerosol performance of the curcumin nanocomposite particles changed depending on the spray drying conditions and several conditions provided better deposition compared with the curcumin original powder. The curcumin nanocomposite particles showed an improved dissolution profile of curcumin compared with the original powder. Furthermore, the curcumin nanocomposite particles showed a higher cytotoxic effect compared with the curcumin original powder towards three cancer cell lines. Curcumin nanocomposite particles containing curcumin nanoparticles show promise as an inhalation formulation for treating lung-related diseases including cancer. PMID- 27374205 TI - Acute cytotoxic effects of marketed ophthalmic formulations on human corneal epithelial cells. AB - The purpose of the study was to devise a fast, reliable and sensitive cell viability assay for assessment of acute cytotoxicity on human corneal epithelial cells by using a clinically relevant exposure time. Acute cytotoxic effects of the pharmaceutical excipients benzalkonium chloride (BAC), macrogolglycerol hydroxystearate (MGHS40), polysorbate 80 (PS80) and marketed ophthalmic formulations (Lumigan((r)), Monoprost((r)), Taflotan((r)), Travatan((r)), Xalatan((r))) containing these excipients were tested. Human corneal epithelial cell (HCE-T) viability was assessed by measuring the reduction of resazurin to highly fluorescent resorufin. Expression of the tight junction proteins in HCE-T cells were characterized by immunofluorescence staining. Presence of tight junction proteins in HCE-T cells was demonstrated. BAC preserved ophthalmic formulations showed concentration-dependent and time-dependent cytotoxicity to human corneal epithelium. In contrast, no acute cytotoxicity of non-ionic stabilizing/solubilizing excipients (MGSH40 and PS80) or ophthalmic formulation containing these excipients was observed. Marketed ophthalmic formulations used for glaucoma medication show differential toxicity on human corneal epithelial cells. The present study revealed that BAC-preserved ophthalmic formulations were able to induce acute cytotoxic effects even during a clinically relevant exposure time, which was not observed with MGSH40 and PS80 excipients or ophthalmic formulations containing these excipients. PMID- 27374206 TI - Timescales of mixing and of chemistry: general discussion. PMID- 27374207 TI - Practice Policy Statement: Integrating Effective Weight Management Into Practice. AB - The American College of Preventive Medicine Prevention Practice Committee contributes to policy guidelines and recommendations on preventive health topics for clinicians and public health decision makers. As an update to a previously published statement on weight management counseling of overweight adults, the College is providing a consensus-based recommendation designed to more effectively integrate weight management strategies into clinical practice and to incorporate referrals to effective evidence-based community and commercial weight management programs. The goal is to empower providers to include lifestyle interventions as part of the foundation of clinical practice. PMID- 27374208 TI - Concomitant Adolescent Vaccination in the U.S., 2007-2012. AB - INTRODUCTION: Concomitant (same-day) delivery of two or more vaccines to adolescents is effective, safe, and efficient. Increasing concomitant vaccination could improve coverage for recommended adolescent vaccines, but little is known about who receives vaccines concomitantly. METHODS: Data came from healthcare provider-verified records on 70,144 adolescents (aged 13-17 years) in the 2008 2012 versions of the National Immunization Survey-Teen who had received at least one dose of tetanus, diphtheria, and acellular pertussis (Tdap) booster; meningococcal conjugate vaccine (MenACWY); or human papillomavirus (HPV) vaccine. Separately for each vaccine, multivariable logistic regression identified adolescent and household correlates of concomitant versus single vaccination, stratified by adolescent sex. Vaccination took place in 2007-2012, data collection in 2008-2012, and data analysis in 2015. RESULTS: Among vaccinated adolescents, 51%-65% of girls and 25%-53% of boys received two vaccines concomitantly. Concomitant uptake of each vaccine increased over survey years (e.g., 2012 vs 2008: girls' Tdap booster, OR=1.88, 95% CI=1.56, 2.26; boys' Tdap booster, OR=2.62, 95% CI=2.16, 3.16), with the exception of HPV vaccination among boys. Additionally, concomitant vaccination was less common as adolescents got older and in the Northeast (all p<0.05). For MenACWY and HPV vaccine, concomitant uptake was less common for girls whose mothers had higher versus lower education and for boys who lived in metropolitan versus non-metropolitan areas (all p<0.05). CONCLUSIONS: Missed opportunities for concomitant adolescent vaccination persist, particularly for HPV vaccine. Future interventions targeting groups with low rates of concomitant vaccination could improve population-level coverage with recommended vaccines. PMID- 27374209 TI - Ambulatory Care-Sensitive Condition Hospitalizations Among Medicare Beneficiaries. AB - INTRODUCTION: This study examined the association between the distribution of primary care physicians and Medicare beneficiaries' ambulatory care sensitive condition hospitalizations using both statistical and spatial analyses. METHODS: Data from the 2014 County Health Rankings, 2013-2014 Area Resource File, and the 2014 Food Environment Atlas Data File were integrated to perform county-level ordinary least squares and geographically weighted regression. Analyses were conducted in late 2015. RESULTS: Primary care physician density was found to be negatively associated with Medicare beneficiaries' ambulatory care sensitive condition hospitalization rate in both ordinary least squares (beta=-5.88, p=0.0037) and geographically weighted regression models (37.08% of all counties), with the latter model finding significant relationships in the South and Northeast. CONCLUSIONS: Preventable hospitalizations are high in areas of the U.S. that have low primary care physician density and other healthcare resources, large non-white populations, high levels of area deprivation, and rural designations. Using geospatial techniques helped document areas of greatest concern for potential intervention. Future research needs to account for these regional differences and target surveillance accordingly. PMID- 27374211 TI - MicroRNA-340 promotes the tumor growth of human gastric cancer by inhibiting cyclin G2. AB - Aberrant expression and function of microRNAs (miRNAs) play a critical role in the development and progression of various human cancers including gastric cancer. However, the clinical significance and underlying mechanisms of miR-340 remain largely unknown in gastric cancer. In the present study, we demonstrated that the expression of miR-340 was aberrantly elevated in both gastric cancer tissues and cells. Moreover clinical association analyses disclosed that the elevated level of miR-340 was significantly associated with unfavorable clinicopathological characteristics of the gastric cancer patients, such as poor differentiation, large tumor size and advanced tumor-node-metastasis (TNM) stage. Gastric cancer patients with high expression of miR-340 had prominently shorter overall survival and disease-free survival. Functionally, forced expression of miR-340 promoted cell viability, proliferation, colony formation and cell cycle progression in the SGC-7901 cells, while miR-340 silencing reduced cell viability, proliferation, colony formation and cell cycle progression in MGC-803 cells. Furthermore, in vivo experiments indicated that miR-340 knockdown suppressed the tumor growth of MGC-803 cells. Notably, alteration of miR-340 expression affected the luciferase activity of wild-type 3'-UTR of cyclin G2 (CCNG2) and regulated CCNG2 abundance in gastric cancer cells, indicating that CCNG2 is a direct target of miR-340. Moreover, CCNG2 knockdown eradicated the effects of miR-340 silencing on gastric cancer cells. In conclusion, our data suggest that miR-340 may potentially serve as a novel prognostic biomarker and therapeutic target for gastric cancer. PMID- 27374210 TI - The landscape of chromosomal aberrations in breast cancer mouse models reveals driver-specific routes to tumorigenesis. AB - Aneuploidy and copy-number alterations (CNAs) are a hallmark of human cancer. Although genetically engineered mouse models (GEMMs) are commonly used to model human cancer, their chromosomal landscapes remain underexplored. Here we use gene expression profiles to infer CNAs in 3,108 samples from 45 mouse models, providing the first comprehensive catalogue of chromosomal aberrations in cancer GEMMs. Mining this resource, we find that most chromosomal aberrations accumulate late during breast tumorigenesis, and observe marked differences in CNA prevalence between mouse mammary tumours initiated with distinct drivers. Some aberrations are recurrent and unique to specific GEMMs, suggesting distinct driver-dependent routes to tumorigenesis. Synteny-based comparison of mouse and human tumours narrows critical regions in CNAs, thereby identifying candidate driver genes. We experimentally validate that loss of Stratifin (SFN) promotes HER2-induced tumorigenesis in human cells. These results demonstrate the power of GEMM CNA analysis to inform the pathogenesis of human cancer. PMID- 27374212 TI - Thyroid hormone: relevance to xenotransplantation. AB - BACKGROUND: It has been well documented that the level of serum/plasma free triiodothyronine (fT3) falls rapidly following brain death or during certain surgical procedures, for example, heart surgery carried out on cardiopulmonary bypass. The level in patients following cardiopulmonary bypass usually recovers within 2 days. METHODS: We have measured serum fT3 in healthy naive baboons (n = 31), healthy naive monkeys (n = 5), and after pig-to-baboon heterotopic heart xenotransplantation (xenoTx) (Group 1, n = 9), orthotopic liver xenoTx (Group 2, n = 10), artery patch xenoTx (Group 3, n = 9), and in monkey-to-monkey heterotopic heart alloTx (Group 4, n = 5). RESULTS: The mean level of fT3 in healthy naive baboons was 3.1 +/- 0.9 pg/ml and in healthy naive monkeys was 2.6 +/- 0.3 pg/ml. Following pig heart, liver, and artery patch xenoTx and monkey heart alloTx, there was an immediate rapid fall in fT3 level. Recovery of fT3 was more rapid in Groups 3 and 4 than in Groups 1 and 2. In Group 1, within 4 days fT3 had recovered, but only to the lower limit of normal range, where it remained throughout follow-up (for up to 42 days). In Group 2, no recovery was seen during the 7 days of follow-up. In immunosuppressed baboons with pig patch grafts that received IL-6R blockade (n = 2), the fT3 tended to rise higher than in those that received no IL-6R blockade (n = 6). CONCLUSIONS: Following operative procedures, there is a dramatic fall in serum fT3 levels. The persistent low level of fT3 after pig heart and liver xenoTx may be associated with a continuing inflammatory state. We suggest that consideration should be given to the replacement of T3 therapy to maintain normal fT3 levels, particularly in nonhuman primates undergoing orthotopic pig heart or liver xenoTx. PMID- 27374213 TI - A rib abnormality mimicking pulmonary nodule: a pitfall in the plain chest x-ray. AB - The ribs show a wide range of normal and pathologic radiographic appearences as well as congenital variations. Intrathoracic ribs are isolated and rare anomalies. They are usually super-numerary, more often right-sided, and involve the middle part of the thorax. We describe a case with intrathorasic rib abnormality mimicking a peripheral metastatic lung nodule in the plain chest x ray and emphasize the use of coronal and sagittal reformatted images in thorasic imaging. Utilisation of multiplanar reformatted images in chest computerised tomography increase diagnostic quality. PMID- 27374214 TI - Bilateral empyema treated by sequential pleuroscopy. AB - Bilateral empyema associated to infectious pericarditis is an extremely rare, yet life-threatening condition. Pleuroscopy-medical thoracoscopy has proved its efficacy in series of patients with empyema. Yet, all reported cases treated by this technique, concerned patients with pleural infection located to a single hemithorax. We present the case of a 71-year-old man with bilateral empyema treated successfully by sequential pleuroscopy, associated to infectious pericarditis. PMID- 27374215 TI - Concurrent sensitization to Aspergillus Fumigatus in tropical pulmonary eosinophilia. AB - Tropical pulmonary eosinophilia (TPE) is characterized by lung tissue and peripheral blood eosinophilia. Serum total IgE is also markedly increased in TPE. However, an association with asthma or other hypersensitivity conditions has not been described. During the diagnostic workup of three patients eventually confirmed to have TPE, hypersensitivity to the fungus, Aspergillus Fumigatus was found. However, there was no evidence of diseases of aspergillus hypersensitivity such as severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA). This association however raises the possibility of a future risk of these potentially serious allergic respiratory manifestations. PMID- 27374216 TI - Incidental finding of bronchial diverticula in a non-smoker population: evaluation on thin-section CT. AB - Bronchial diverticula have been described as a common radiological finding in smoker patients with COPD, but the specificity of this sign should be further investigated. Thus, the aim of our study was to evaluate the prevalence of diverticula in a cohort of non-smoker subjects. Between February and July 2012, 2438 patients were admitted to our Radiology Unit to undergo a chest CT. Among them, we enrolled 121 non-smoking patients (78/121-64.5% females, 43/121-35.5% males), of different age (57.0+/-20.7 years-range: 12-88), without any respiratory symptoms, submitted to chest CT for several reasons (oncologic evaluation: 59/121-48.8%; follow up of lung nodules: 27/121-22.3%; screening in connectivitis: 12/121-9.9%; others: 23/121-19.0%). We considered thin-section CT scan on axial, coronal and sagittal plans to evaluate prevalence, numbers and level of bronchial diverticula. Diverticula were found in 41/121-33.9% patients, with a slight major prevalence in males (p=0.048), but no significant difference on age. In 31/41-75.6% the number was <3, whereof 17/31-54.8% with just one diverticulum assessed. Regarding the level, in 30/41-73.2% they were subcarinal, but they were also detected in mainstem (2/41-4.9%) and lobar bronchi (with the right upper lobe bronchus most frequently involved- 12/41-29.3%). Bronchial diverticula can be observed in non-smokers, as well as in smoker patients with COPD. However, their prevalence seems to be lower than in smokers and they tend to be isolated and subcarinal. The age of patients does not influence their finding. More studies should be proposed to better define a cut-off between smokers and healthy subjects. PMID- 27374217 TI - Critical review of the equations predicting 6-minute walking distance in obese subjects. AB - The correlation between the 6-minute walking distance and obesity has been only partially explored. Results obtained from the existing predictive equations are influenced by a variety of factors (health status, severity of obesity, reduced muscle strength and mobility, decreased aerobic capacity, presence of comorbidities). The aim of our study was to verify, compare and discuss the 6MWD predictive capacity of the equations currently available in the literature in a sample of obese subjects. Despite similar study design, the considered articles varied with regard to the number of individuals included and to age range. None of the equations available in the literature was able to accurately predict the six-minute walked distance performed by the obese subjects involved in our study. The six-minute walked distance performed by obese subjects seems to be influenced by other factors than the variables included in the equations from the literature, suggesting that they may not thoroughly capture the complexity of disability in obese people. Future research should be designed in order to validate population-specific equations, by including variables related to clinical, functional, and psychological areas, which are usually impaired in obese individuals. PMID- 27374218 TI - Multum non multa: airway distensibility by forced oscillations. AB - Airway distensibility although appears to be unaffected by airway smooth muscle tone probably related to airway remodelling, after bronchodilator treatment is significantly increased in subjects with asthma. We assessed airway distensibity and its first moment derivative in two patients with mild intermittent asthma and normal spirometry. The increase in airway distensibility after bronchodilation measured at the tidal volume range during quiet breathing by forced oscillations was not accompanied by a change in its first moment, while the latter showed a significant increase in a second patient after anti-inflammatory treatment. It appears that airway distensibility is sensitive to reduction of bronchial smooth muscle tone after bronchodilation, but in addition its first moment might provide information on a change of both bronchial smooth muscle tone and small airways inflammation. PMID- 27374219 TI - Endobronchial Watanabe Spigot in the treatment of bronchobiliary fistula. AB - Bronchobiliary fistula (BBF) is a rare condition in which an abnormal communication exists between the bile ducts and the bronchial tree. Malignancy is the most common etiology of BBF, although many others are possible. A 74-year-old male patient with an inoperable Klatskin tumor presented with a complaint of yellow-green sputum and cough; the patient underwent fiber-optic bronchoscopy based on a preliminary diagnosis of bronchobiliary fistula. Using fiber-optic rigid bronchoscopy, the laterobasal segment of the lower right lung lobe was occluded using three pieces of 5-mm Endobronchial Watanabe Spigot. Bile drainage subsequently ceased. A bronchoscopic approach provides an alternative option for BBF treatment, particularly in patients who choose not to undergo surgery, or for whom surgery is not an option due to their underlying general condition. PMID- 27374220 TI - Delayed functional improvement after near-fatal bleeding complication following endobronchial valve therapy for emphysema. AB - Endoscopic treatment of emphysema is supported by different methods, including valves, coils and sealants. The mechanism is mainly related to volume reduction of targeted area. Endobronchial valves (EBV) appear the most studied method. In a multicentre randomised study, placement of unidirectional endobronchial valves resulted in a statistically significant functional improvement in the treated cohort compared to the control. Adverse events, occurring post procedure, included COPD exacerbations, haemoptysis, pneumothorax and pneumonia. In our centre we treated 30 patients, between January 2009 and February 2012, with variable improvement of lung function and only mild postoperative complications. The case we report here appears very interesting for the unusual near-fatal complication (massive alveolar haemorrage) followed by delayed strong functional improvement (FEV1 +23%; RV -18%; 6MWD:+33%) six months after the valve placement. This improvement could be attributable to the EBV procedure, but an alternative explanation is that the lung volume reduction may have been enhanced by the complication itself, as an effect of alveolar collapse. PMID- 27374221 TI - [Skin tumors in children]. AB - The presence of a congenital or acquired cutaneous lesion is a frequent reason for consultation in pediatric plastic surgery unit. The management of these lesions requires a good knowledge of specific diagnoses in children. This step is sometimes difficult because of the multiplicity of possible diagnosis. Some skin tumors may be the external sign of a general disease or an underlying malformation; those can change the overall prognosis and management and require to be properly identified. The decision of surgical excision depends on various criteria, including diagnosis but also the reconstruction possibilities. The timing of surgical treatment depends on the medical emergency of the tumor resection (benign tumor, spontaneously regressive tumor, risk of degeneration into malignancy), on the cosmetic and psychological impact but also on the growth or learning steps in child life. This article first provides an aid in the diagnosis of the most common or more characteristic skin tumors. The algorithm is principally based on the pigmentation aspect of the tumor. The age and conditions of the surgical management are specified for each type of tumor. Cutaneous hemangiomas and vascular malformations, and congenital cysts and fistulas are not reported in this article. PMID- 27374222 TI - Dietary high oleic canola oil supplemented with docosahexaenoic acid attenuates plasma proprotein convertase subtilisin kexin type 9 (PCSK9) levels in participants with cardiovascular disease risk: A randomized control trial. AB - Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a novel circulating protein which plays an important role in regulation of cholesterol metabolism by promoting hepatic LDL receptor degradation. However, the action of dietary fat composition on PCSK9 levels remains to be fully elucidated. The objective was to investigate the action of different dietary oils on circulating PCSK9 levels in the Canola Oil Multicenter Intervention Trial (COMIT). COMIT employed a double blinded crossover randomized control design, consisting of five 30-d treatment periods. Diets were provided based on a 3000Kcal/d intake, including a 60g/d treatment of conventional canola oil (Canola), a high oleic canola/DHA oil blend (CanolaDHA), a corn/safflower oil blend (CornSaff), a flax/safflower oil blend (FlaxSaff) or a high oleic canola oil (CanolaOleic). Plasma PCSK9 levels were assessed using ELISA at the end of each phase. Lipid profiles (n=84) showed that CanolaDHA feeding resulted in the highest (P<0.05) serum total cholesterol (TC, 5.06+/-0.09mmol/L) and LDL-cholesterol levels (3.15+/-0.08mmol/L) across all five treatments. CanolaDHA feeding also produced the lowest (P<0.05) plasma PCSK9 concentrations (216.42+/-8.77ng/mL) compared to other dietary oil treatments. Plasma PCSK9 levels positively correlated (P<0.05) with serum TC, LDL cholesterol, apolipoprotein A, and apolipoprotein B levels but did not correlate to HDL-cholesterol levels. Results indicate that post-treatment response in PCSK9 may be altered with the CanolaDHA diet. In conclusion, the elevated LDL-C levels from a DHA oil treatment may not be relevant for the observed decline in PCSK9 levels. PMID- 27374223 TI - Oncolytic Virus-Mediated Targeting of PGE2 in the Tumor Alters the Immune Status and Sensitizes Established and Resistant Tumors to Immunotherapy. AB - Immunotherapies are highly promising cancer treatments, but understanding the factors mediating their resistance remains critical. Successes in randomized clinical testing have supported the growing appreciation that oncolytic virotherapies primarily act as immunotherapies. Here we identified prostaglandin E2 (PGE2) in the tumor as a key mediator of resistance to immunotherapies, including oncolytic vaccinia virotherapy. Elevated levels of PGE2 coupled to suppressive chemokine profiles and high levels of granulocytic myeloid-derived suppressor cells resulted in loss of immunotherapeutic potential. Viral vectors engineered to target PGE2 were capable of overcoming localized immunosuppression leading to profound changes in the tumor's immune status. This allowed the viral vectors to raise robust anti-tumor adaptive immune responses and sensitized established and previously resistant tumors to immunotherapies. PMID- 27374224 TI - Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen Presenting Cell Features in Early-Stage Human Lung Cancer. AB - Based on studies in mouse tumor models, granulocytes appear to play a tumor promoting role. However, there are limited data about the phenotype and function of tumor-associated neutrophils (TANs) in humans. Here, we identify a subset of TANs that exhibited characteristics of both neutrophils and antigen-presenting cells (APCs) in early-stage human lung cancer. These APC-like "hybrid neutrophils," which originate from CD11b(+)CD15(hi)CD10(-)CD16(low) immature progenitors, are able to cross-present antigens, as well as trigger and augment anti-tumor T cell responses. Interferon-gamma and granulocyte-macrophage colony stimulating factor are requisite factors in the tumor that, working through the Ikaros transcription factor, synergistically exert their APC-promoting effects on the progenitors. Overall, these data demonstrate the existence of a specialized TAN subset with anti-tumor capabilities in human cancer. PMID- 27374225 TI - Id2 and E Proteins Orchestrate the Initiation and Maintenance of MLL-Rearranged Acute Myeloid Leukemia. AB - E proteins and their antagonists, the Id proteins, are transcriptional regulators important for normal hematopoiesis. We found that Id2 acts as a key regulator of leukemia stem cell (LSC) potential in MLL-rearranged acute myeloid leukemia (AML). Low endogenous Id2 expression is associated with LSC enrichment while Id2 overexpression impairs MLL-AF9-leukemia initiation and growth. Importantly, MLL AF9 itself controls the E-protein pathway by suppressing Id2 while directly activating E2-2 expression, and E2-2 depletion phenocopies Id2 overexpression in MLL-AF9-AML cells. Remarkably, Id2 tumor-suppressive function is conserved in t(8;21) AML. Low expression of Id2 and its associated gene signature are associated with poor prognosis in MLL-rearranged and t(8;21) AML patients, identifying the Id2/E-protein axis as a promising new therapeutic target in AML. PMID- 27374227 TI - Long non-coding RNA Malat1 promotes neurite outgrowth through activation of ERK/MAPK signalling pathway in N2a cells. AB - Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are playing critical roles in neurogenesis, yet the underlying molecular mechanisms remain largely elusive. Neurite outgrowth is an early step in neuronal differentiation and regeneration. Using in vitro differentiation of neuroblastoma-derived Neuro 2a (N2a) cell as a model, we performed expression profiling to identify lncRNAs putatively relevant for neurite outgrowth. We identified that Metastasis associated lung adenocarcinoma transcript 1 (Malat1) was one of the most significantly up-regulated lncRNAs during N2a cell differentiation. Malat1 knockdown resulted in defects in neurite outgrowth as well as enhanced cell death. To pinpoint signalling pathways perturbed by Malat1 depletion, we then performed a reporter-based screening to examine the activities of 50 signalling pathways in Malat1 knockdown cells. We found that Malat1 knockdown resulted in conspicuous inhibition of Mitogen-Activated Protein Kinase (MAPK) signaling pathway as well as abnormal activation of Peroxisome proliferator-activated receptor (PPAR) and P53 signalling pathway. Inhibition of ERK/MAPK pathway with PD98059 potently blocked N2a cell neurite outgrowth, whereas phorbol 12-myristate 13-acetate-induced ERK activation rescued defects in neurite outgrowth and cell death induced by Malat1 depletion. Together, our results established a critical role of Malat1 in the early step of neuronal differentiation through activating ERK/MAPK signalling pathway. PMID- 27374228 TI - Break a neck. PMID- 27374229 TI - Post-operative analgesia: focus has been on benefit - are we forgetting the harm? PMID- 27374230 TI - Insights into the biological features of the antigenic determinants recognized by four monoclonal antibodies in redia and adult stages of the liver fluke Fasciola hepatica. AB - Fasciola hepatica is a digenean trematode which infects a wide variety of domestic animals and also humans. Previous studies have demonstrated that four monoclonal antibodies (Mabs) against the total extract of F. hepatica redia (named as 1E4, 6G11, 4E5 and 4G11) also recognized the excretion - secretion antigens (ES Ag) of adult parasites, which is a biologically-relevant mixture of molecules with functional roles during infection and immune evasion on definitive hosts. In the present report we describe the partial characterization of the epitopes recognized by these Mabs by heat treatment, mercaptoethanol reduction, pronase proteolysis and sodium peryodate oxidation, which suggested their predominant protein and conformational nature. Also, a comparative study using immunodetection assays on crude extracts and on histological sections of both rediae and adults of F. hepatica were performed to explore the expression pattern of the antigenic determinants in these developmental stages. From these experiments it was found that the Mabs reacted most likely with the same proteins of approximately 64 and 105 kDa present on both rediae and adult's extracts. However, the 1E4, 6G11 and 4E5 Mabs also recognized other molecules of the total extract of F. hepatica adults, a fact that constitutes an evidence of the antigenic variation between both stages and points at a certain biological relevance of the recognized antigenic determinants. Immunolocalization studies on histological sections revealed that all Mabs reacted with the tegument of F. hepatica in both rediae and adults stages, while the epitopes recognized by 1E4, 6G11 and 4E5 antibodies were also preferentially localized in the intestinal caeca and in different organs of the reproductive system of adult specimens. The immunogenicity of these antigenic determinants, their conserved status among different stages of the life cycle of F. hepatica and their presence in both tegument and ES Ag of adult parasites, are suitable features that suggest their potential use for developing an epitope-based vaccine for fasciolosis control. PMID- 27374231 TI - Diabetic uropathy and bladder dysfunctions. PMID- 27374232 TI - A systematic High-Content Screening microscopy approach reveals key roles for Rab33b, OATL1 and Myo6 in nanoparticle trafficking in HeLa cells. AB - Synthetic nanoparticles are promising tools for imaging and drug delivery; however the molecular details of cellular internalization and trafficking await full characterization. Current knowledge suggests that following endocytosis most nanoparticles pass from endosomes to lysosomes. In order to design effective drug delivery strategies that can use the endocytic pathway, or by-pass lysosomal accumulation, a comprehensive understanding of nanoparticle uptake and trafficking mechanisms is therefore fundamental. Here we describe and apply an RNA interference-based high-content screening microscopy strategy to assess the intracellular trafficking of fluorescently-labeled polystyrene nanoparticles in HeLa cells. We screened a total of 408 genes involved in cytoskeleton and membrane function, revealing roles for myosin VI, Rab33b and OATL1 in this process. This work provides the first systematic large-scale quantitative assessment of the proteins responsible for nanoparticle trafficking in cells, paving the way for subsequent genome-wide studies. PMID- 27374233 TI - Interosseous membrane reconstruction with a suture-button construct for treatment of chronic forearm instability. AB - BACKGROUND: The purpose of this study was to report outcomes of interosseous membrane (IOM) reconstruction with a suture-button construct for treatment of chronic longitudinal forearm instability. METHODS: We performed a retrospective review with prospective follow-up of patients who underwent ulnar shortening osteotomy and IOM reconstruction with the Mini TightRope device from 2011 through 2014. Bivariate statistical analysis was used for comparison of preoperative and postoperative Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) scores, range of motion, grip strength, and ulnar variance. Complications and patient satisfaction were also recorded. RESULTS: Ten patients (mean age, 45.3 years) satisfied inclusion criteria: 8 treated for post-traumatic sequelae of Essex-Lopresti-type injuries, 1 for forearm instability secondary to previous elbow surgery, and 1 for instability secondary to trauma and multiple elbow surgeries. Surgeries were performed an average of 28.6 months from initial injury. At mean follow-up of 34.6 months after surgery, significant improvement was observed in elbow flexion-extension arc (+23 degrees vs. preoperatively; P = .007), wrist flexion-extension arc (+22 degrees ; P = .016), QuickDASH score ( 48; P = .000), and ulnar variance (-3.3 mm; P = .006). Three patients required additional surgery: 1 revision ulnar shortening osteotomy for persistent impingement, 1 revision ulnar osteotomy and Mini TightRope removal for lost forearm supination, and 1 fixation of a radial shaft fracture after a fall. CONCLUSION: IOM reconstruction using a suture-button construct is an effective treatment option for chronic forearm instability. PMID- 27374234 TI - Dynamic contrast-enhanced ultrasound and elastography assess deltoid muscle integrity after reverse shoulder arthroplasty. AB - BACKGROUND: The outcome after reverse shoulder arthroplasty (RSA) depends on the condition of the deltoid muscle, which we assessed with new ultrasound modalities and electromyography (EMG). Contrast-enhanced ultrasound (CEUS) and acoustic radiation force impulse (ARFI) were applied to assess perfusion and elasticity of the deltoid muscle compared with the clinical and functional outcome. METHODS: The study recruited 64 patients (mean age, 72.9 years) treated with RSA between 2004 and 2013. The deltoid muscle was examined with EMG and ultrasound imaging. Functional scores such as Constant score and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form score were assessed. Among other CEUS parameters, the wash-in perfusion index, time to peak, and rise time were compared between the operated-on and contralateral shoulders as well as between patients with above-average and below-average outcome. The stiffness of the deltoid muscle was analyzed with ARFI. RESULTS: After RSA, deltoid perfusion (wash-in perfusion index, Delta = -12% +/- 22%, P = .0001) and shoulder function (Constant score, Delta = -14 +/- 24, P < .0001) were both inferior compared with the contralateral side. This perfusion deficit was associated with a limited range of motion (time to peak and anteversion: r = -0.290, P = .022). Deltoid perfusion was higher in patients with above-average outcome (rise time, Delta = 33% +/- 13%, P = .038). The operated-on deltoid muscles showed higher stiffness than the contralateral muscles (ARFI, Delta = 0.2 +/- 0.9 m/s, P = .0545). EMG excluded functionally relevant axillary nerve injuries in the study population. CONCLUSIONS: CEUS revealed reduced mean perfusion of the deltoid muscle after RSA. Reduced perfusion was associated with limited range of motion and below average outcome. Functional shoulder impairment after RSA might be predicted by noninvasive CEUS as a surrogate parameter for the integrity of the deltoid muscle. PMID- 27374235 TI - Implant positioning in reverse shoulder arthroplasty has an impact on acromial stresses. AB - BACKGROUND: Acromial fractures after reverse shoulder arthroplasty (RSA) have been reported to occur in up to 7% of patients. Whereas RSA implant parameters can be configured to alter stability, range of motion, and deltoid mechanical advantage, little is known about the effect of these changes on acromial stresses. The purpose of this finite element study, therefore, was to evaluate the effect of RSA humeral and glenoid implant position on acromial stresses. METHODS: Solid body models of 10 RSA reconstructed cadaveric shoulders (38-mm glenosphere, 155 degrees neck-shaft angle) were input into custom software that calculated the deltoid force required to achieve an abduction arc of motion (0 degrees -120 degrees ). The resulting forces were applied to a finite element study model of the scapula to ascertain the acromial stress distribution. This process was repeated for varying glenoid inferiorizations (0, +2.5, +5.0 mm), lateralizations (0, +5.0, +10.0 mm), and humeral lateralizations (-5.0, 0, +5.0 mm). RESULTS: Glenosphere inferiorization decreased maximum principal stress in the acromion by 2.6% (0.7 +/- 0.2 MPa; P = .007). Glenosphere lateralization produced a greater effect, increasing stress by 17.2% (4.1 +/- 0.9 MPa; P = .001). Humeral lateralization caused an insignificant increase in stress by 1.7% (0.5 +/- 0.2 MPa; P = .066), and humeral medialization decreased stress by 1.4% (0.8 +/- 0.3 MPa; P = .038). The highest acromial stresses occurred in the region where fractures most commonly occur, Levy type II, at 33.7 +/- 3.81 MPa (P < .001). CONCLUSIONS: Glenosphere positioning has a significant effect on acromial stress after RSA. Inferior and medial positioning of the glenosphere serves to decrease acromial stress, thought to be primarily due to increased deltoid mechanical advantage. The greatest effect magnitudes are seen at lower abduction angles, where the humerus is more frequently positioned. PMID- 27374236 TI - Relative scapular muscle activity ratios are altered in subacromial pain syndrome. AB - BACKGROUND: Coordinated muscle activity is needed for synchronized joint motion and stability. Characterizing relative scapular muscle activity deficits in participants with shoulder pain will provide foundational knowledge to develop rehabilitation programs. METHODS: Participants were recruited with subacromial pain syndrome and an asymptomatic control group matched for age, gender, and dominant arm (N = 56). Surface electromyographic muscle activity was recorded from the upper, middle, and lower trapezius (UT, MT, LT) and serratus anterior (SA) during 5 repetitions of a weighted arm elevation task. Muscle activity was normalized to a reference contraction and then expressed as UT/MT, UT/LT, UT/SA, and LT/SA ratios. Ratios were compared between groups and across 3 arm angle intervals during ascending and descending elevation. RESULTS: A 2 * 3 mixed-model analysis of variance yielded a group main effect for the UT/LT ratio, with a higher ratio in the subacromial pain group during ascending (mean difference, 0.92; P = .008) and descending (mean difference, 0.70; P = .030). For the LT/SA ratio, there was a group effect: a lower ratio in the subacromial group during ascending (mean difference, -0.25; P = .026) and descending (mean difference, 0.51; P = .032). There were no differences for the UT/MT or UT/SA. DISCUSSION: There is a disruption in coordination between the LT and SA and the UT and LT during an arm elevation task in patients with subacromial pain syndrome. The LT was part of both altered ratios, indicating the relative importance of the LT. Future research should determine if exercises aimed at restoring the dysfunctional LT/SA and UT/LT force couples are beneficial to reduce shoulder pain and disability in patients with unilateral shoulder pain. PMID- 27374237 TI - Hypertrophic teres minor restores shoulder strength and range of external rotation in posterosuperior rotator cuff tears. AB - BACKGROUND: In posterosuperior rotator cuff tears (PS-RCT), the progression of infraspinatus (ISP) muscle atrophy seems to induce compensatory hypertrophy of the teres minor (TM) muscles. However, the effect of these changes on shoulder strength and range of external rotation (ER) remains unclear. This study determined the strength and range of ER in patients with PS-RCT with atrophic ISP and hypertrophic TM and compared this with patients with PS-RCT and normal or deficient TM. METHODS: We investigated 35 patients with PS-RCT and atrophic ISP. TM muscles were classified as hypertrophic (type A) in 17, normal (type B) in 10, or deficient (type C) in 8. The strength ratio of the affected shoulder to the healthy contralateral shoulder was calculated, and the active range of motion was measured for both shoulders. RESULTS: The strength ratios of ER in types A, B, and C were 60%, 33%, and 7% (P < .01) with the patient's arm at the side and were 60%, 35%, and 5% (P < .001) at 90 degrees abduction, respectively. The average ranges of ER in types A, B, and C were 22.6 degrees , 15.0 degrees , and -12.5 degrees (P < .001) with the patient's arm at the side and were 71.6 degrees , 44.5 degrees , and 21.9 degrees at 90 degrees abduction (P < .01), respectively. The differences between shoulder types in other measures of strength or ER range were not significant. CONCLUSIONS: In patients with PS-RCT and atrophic ISP, shoulders with compensatory hypertrophy of the TM had greater strength and range of ER than shoulders with normal or atrophic TM. PMID- 27374238 TI - Atrial fibrillation associated hospitalizations in patients with end-stage renal disease in the United States, 2003-2012. AB - BACKGROUND: Atrial fibrillation (AF) is highly prevalent in patients with end stage renal disease (ESRD). The clinical and economic burden of AF-associated hospitalizations has not been previously quantified in the ESRD population in the United States. OBJECTIVE: The aim of this study was to assess the incidence and outcomes of AF hospitalizations in the US ESRD population. METHODS: We used the 2003-2012 National Inpatient Sample database to study trends in the incidence and outcomes of AF hospitalizations in ESRD patients. Primary outcomes included hospitalization rate, in-hospital case fatality ratio (CFR), length of stay (LOS), and cost. RESULTS: There were 66,811 primary and 986,742 secondary AF hospitalizations associated with ESRD. The mean age of the patients was 70.9 years, and 45.2% were women. The age-adjusted primary AF hospitalization rate increased from 10.1 to 14.0 per 1000 ESRD patients, while the secondary AF hospitalization rate increased from 164.0 to 212.8 per 1000 ESRD patients (P trend < 0.05 for both). There was a significant decrease in CFR (2.9%-2.7% for primary AF and 11.3%-7.7% for secondary AF; P-trend < .001 for both), mean LOS (6.0-4.8 days for primary AF and 9.8-7.1 days for secondary AF; P-trend < .001 for both), and mean cost ($14,395-$11,184 for primary AF and $25,545-$17,879 for secondary AF; P-trend < .001 for both). CONCLUSION: There was a greater than 2 fold increase in the annual number of AF hospitalizations along with a significant increase in AF hospitalization rate in the US ESRD population. There were significant improvements in markers of quality of care, including inhospital CFR, LOS, and cost. PMID- 27374239 TI - Safety evaluation of a leadless transcatheter pacemaker for magnetic resonance imaging use. AB - BACKGROUND: Increased magnetic resonance imaging (MRI) adoption and demand are driving the need for device patients to have safe access to MRI. OBJECTIVE: The aim of this study was to address the interactions of MRI with the Micra transcatheter pacemaker system. METHODS: A strategy was developed to evaluate potential MRI risks including device heating, unintended cardiac stimulation, force, torque, vibration, and device malfunction. Assessment of MRI-induced device heating was conducted using a phantom containing gelled saline, and Monte Carlo simulations incorporating these results were conducted to simulate numerous combinations of human body models, position locations in the MRI scanner bore, and a variety of coil designs. Lastly, a patient with a Micra pacemaker who underwent a clinically indicated MRI scan is presented. RESULTS: Compared to traditional MRI conditional pacemakers, the overall risk with Micra was greatly reduced because of the small size of the device and the absence of a lead. The modeling results predicted that the nonperfused temperature rise of the device would be less than 0.4 degrees C at 1.5 T and 0.5 degrees C at 3 T and that the risk of device heating with multiple device implants was not increased as compared with a single device. The clinical case study revealed no MRI-related complications. CONCLUSION: The MRI safety assessment tests conducted for the Micra pacemaker demonstrate that patients with a single device or multiple devices can safely undergo MRI scans in both 1.5- and 3-T MRI scanners. No MRI related complications were observed in a patient implanted with a Micra pacemaker undergoing a clinically indicated scan. PMID- 27374240 TI - Human neural stem cell-induced endothelial morphogenesis requires autocrine/paracrine and juxtacrine signaling. AB - Transplanted neural stem cells (NSC) interact with the host brain microenvironment. A neovascularization is commonly observed in the vicinity of the cell deposit, which is correlated with behavioral improvements. To elucidate the signaling mechanisms between human NSCs and endothelial cells (ECs), these were cocultured in an in vitro model in which NSC-induced endothelial morphogenesis produced a neurovascular environment. Soluble (autocrine/paracrine) and contact-mediated (juxtacrine) signaling molecules were evaluated for two conditionally immortalized fetal NSC lines derived from the cortical anlage (CTXOE03) and ganglionic eminence (STROC05), as well as an adult EC line (D3) derived from the cerebral microvasculature of a hippocampal biopsy. STROC05 were 4 times as efficient to induce endothelial morphogenesis compared to CTXOE03. The cascade of reciprocal interactions between NSCs and ECs in this process was determined by quantifying soluble factors, receptor mapping, and immunocytochemistry for extracellular matrix molecules. The mechanistic significance of these was further evaluated by pharmacological blockade. The sequential cell-specific regulation of autocrine/paracrine and juxtacrine signaling accounted for the differential efficiency of NSCs to induce endothelial morphogenesis. These in vitro studies shed new light on the reciprocal interactions between NSCs and ECs, which are pivotal for our mechanistic understanding of the efficacy of NSC transplantation. PMID- 27374241 TI - A cascade screening approach for the identification of Bcr-Abl myristate pocket binders active against wild type and T315I mutant. AB - The major clinical challenge in drug-resistant chronic myelogenous leukemia (CML) is currently represented by the Bcr-Abl T315I mutant, which is unresponsive to treatment with common first and second generation ATP-competitive tyrosine kinase inhibitors (TKIs). Allosteric inhibition of Bcr-Abl represent a new frontier in the fight against resistant leukemia and few candidates have been identified in the last few years. Among these, myristate pocket (MP) binders discovered by Novartis (e.g. GNF2/5) showed promising results, although they proved to be active against the T315I mutant only in combination with first and second generation ATP-competitive inhibitors. Here we used a cascade screening approach based on sequential fluorescence polarization (FP) screening, in silico docking/dynamics studies and kinetic-enzymatic studies to identify novel MP binders. A pyrazolo[3,4-d]pyrimidine derivative (6) has been identified as a promising allosteric inhibitor active on 32D leukemia cell lines (expressing Bcr Abl WT and T315I) with no need of combination with any ATP-competitive inhibitor. PMID- 27374242 TI - Anti-inflammatory polyphenol constituents derived from Cissus pteroclada Hayata. AB - A new bergenin derivative, bergenin-11-O-alpha-d-galactopyranoside (compound 1), together with seven known polyphenolic compounds, were isolated from the stem of Cissus pteroclada Hayata. The structures of the 8 compounds were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Moreover, the in vitro anti-inflammatory effects of compounds (1-8) in LPS-stimulated murine macrophage RAW 264.7 cells were also investigated. Our results revealed that compound 1 inhibited the production of pro-inflammatory mediators NO and PGE2 and the expression of NF-kappaB, TNF-alpha, IL-1beta, iNOS and COX-2. PMID- 27374244 TI - Decoupling order and conductivity in doped conducting polymers. AB - Herein it is demonstrated that the high level of interchain ordering of pEDOT is not necessary for the polymer to have efficient charge transport. Resistance and order are compared during the manufacturing process, where the polymerisation step and ordering step are decoupled as separate stages of the processing. GIWAXS experiments measuring interchain order are correlated to resistivity measurements at multiple stages of the manufacturing process on single films, and it is shown that for an individual film, where percolation is achieved, having a long range ordered system offers no reduction in resistance compared to having a highly disordered state of the same film. For this system, once the chains of pEDOT are formed, it is experimentally demonstrated that for percolation to be achieved, a remarkably low 4.5% volume fraction pEDOT is required. The apparent lack of necessity for significant interchain ordering allows for a meaningful measurement of development of the charge transport during the chemical polymerisation process. PMID- 27374243 TI - Insights into the structure-activity relationship of the anticancer compound ZJ 101, a derivative of marine natural product superstolide A: A critical role played by the conjugated trienyl lactone moiety. AB - Compound ZJ-101, a structurally simplified analog of the marine natural product superstolide A, was previously developed in our laboratory. In the subsequent structure-activity relationship study, two new analogs, ZJ-105 and ZJ-106, were designed and synthesized to probe the importance of the conjugated trienyl lactone moiety of the molecule by replacing the C2-C3 double bond in ZJ-101 with a single bond and switching the geometry of the C4-C5 double bond in ZJ-101 from Z to E, respectively. Biological evaluation showed that ZJ-105 completely loses antiproliferative activity whereas ZJ-106 is significantly less active against cancer cells in vitro than ZJ-101, suggesting that the conjugated trienyl lactone moiety of the molecule is critical for its anticancer activity. PMID- 27374245 TI - Universal evolution of a viscous-capillary spreading drop. AB - The rate of spreading or retraction of a drop on a flat substrate is determined through a balance of surface tension and hydrodynamic flow. While asymptotic regimes are known, no general rate equation has hitherto been available. Here, we revisit this classic problem, in a regime governed by capillary and viscous forces, by performing an exhaustive numerical study of drop evolution as a function of the contact angle with the substrate. Our study reveals a universal evolution of the drop radius parameterised only by the substrate wettability. Two limits of this evolution recover the familiar exponential and algebraic regimes. Our results show quantitative comparison with the evolution derived from lubrication theory, indicating that dissipation at the contact line is the key determinant in drop evolution. Our work, both numerical and theoretical, provides a foundation for studying the full temporal dynamics of droplet evolution under the influence of external fields and thermal fluctuations, which are of importance in nanofluidics. PMID- 27374246 TI - The future is in the numbers: the power of predictive analysis in the biomedical educational environment. AB - Biomedical programs have a potential treasure trove of data they can mine to assist admissions committees in identification of students who are likely to do well and help educational committees in the identification of students who are likely to do poorly on standardized national exams and who may need remediation. In this article, we provide a step-by-step approach that schools can utilize to generate data that are useful when predicting the future performance of current students in any given program. We discuss the use of linear regression analysis as the means of generating that data and highlight some of the limitations. Finally, we lament on how the combination of these institution-specific data sets are not being fully utilized at the national level where these data could greatly assist programs at large. PMID- 27374247 TI - Toward best practice in Human Machine Interface design for older drivers: A review of current design guidelines. AB - Older adults are the fastest growing segment of the driving population. While there is a strong emphasis for older people to maintain their mobility, the safety of older drivers is a serious community concern. Frailty and declines in a range of age-related sensory, cognitive, and physical impairments can place older drivers at an increased risk of crash-related injuries and death. A number of studies have indicated that in-vehicle technologies such as Advanced Driver Assistance Systems (ADAS) and In-Vehicle Information Systems (IVIS) may provide assistance to older drivers. However, these technologies will only benefit older drivers if their design is congruent with the complex needs and diverse abilities of this driving cohort. The design of ADAS and IVIS is largely informed by automotive Human Machine Interface (HMI) guidelines. However, it is unclear to what extent the declining sensory, cognitive and physical capabilities of older drivers are addressed in the current guidelines. This paper provides a review of key current design guidelines for IVIS and ADAS with respect to the extent they address age-related changes in functional capacities. The review revealed that most of the HMI guidelines do not address design issues related to older driver impairments. In fact, in many guidelines driver age and sensory cognitive and physical impairments are not mentioned at all and where reference is made, it is typically very broad. Prescriptive advice on how to actually design a system so that it addresses the needs and limitations of older drivers is not provided. In order for older drivers to reap the full benefits that in-vehicle technology can afford, it is critical that further work establish how older driver limitations and capabilities can be supported by the system design process, including their inclusion into HMI design guidelines. PMID- 27374249 TI - International Committee on Systematics of Prokaryotes Subcommittee on the taxonomy of Halomonadaceae, Minutes of the closed meeting, 23 May 2016, San Juan, Puerto Rico. PMID- 27374250 TI - Reproducibility of data-driven dietary patterns in two groups of adult Spanish women from different studies. AB - The objective of the present study was to assess the reproducibility of data driven dietary patterns in different samples extracted from similar populations. Dietary patterns were extracted by applying principal component analyses to the dietary information collected from a sample of 3550 women recruited from seven screening centres belonging to the Spanish breast cancer (BC) screening network (Determinants of Mammographic Density in Spain (DDM-Spain) study). The resulting patterns were compared with three dietary patterns obtained from a previous Spanish case-control study on female BC (Epidemiological study of the Spanish group for breast cancer research (GEICAM: grupo Espanol de investigacion en cancer de mama)) using the dietary intake data of 973 healthy participants. The level of agreement between patterns was determined using both the congruence coefficient (CC) between the pattern loadings (considering patterns with a CC>=0.85 as fairly similar) and the linear correlation between patterns scores (considering as fairly similar those patterns with a statistically significant correlation). The conclusions reached with both methods were compared. This is the first study exploring the reproducibility of data-driven patterns from two studies and the first using the CC to determine pattern similarity. We were able to reproduce the EpiGEICAM Western pattern in the DDM-Spain sample (CC=0.90). However, the reproducibility of the Prudent (CC=0.76) and Mediterranean (CC=0.77) patterns was not as good. The linear correlation between pattern scores was statistically significant in all cases, highlighting its arbitrariness for determining pattern similarity. We conclude that the reproducibility of widely prevalent dietary patterns is better than the reproducibility of more population specific patterns. More methodological studies are needed to establish an objective measurement and threshold to determine pattern similarity. PMID- 27374252 TI - The capacity to tell a joke: Reflections from work with Asperger children. AB - The capacity to tell a joke is a highly complex interpersonal event that depends upon the maturation of certain developmental achievements which are absent or stunted in children with Asperger's Syndrome. These include the ability to know another's mind, a sense of interpersonal timing and, most notably, a capacity for abstract thinking. The author discusses Freud's () notion of joke-work, which is akin to dream-work, both of which are pathways to forming mental representations. Freud considered joke-work as a mental activity that operated on the verbal level and the author examines the preverbal dimensions that are rooted in the earliest mother/infant interactions. An extended case discussion of the psychoanalytic treatment of an Asperger boy is offered to illustrate these points and to demonstrate the activity of joke-work as a means of building mental representations. PMID- 27374251 TI - Dietary Patterns and Type 2 Diabetes Mellitus in a First Nations Community. AB - BACKGROUND: Type 2 diabetes mellitus is a growing concern worldwide, particularly in Indigenous communities, which have undergone a marked nutrition transition characterized by reduced intakes of traditional foods and increased intakes of market foods. Few studies have assessed the relationships between differing dietary patterns and risk for type 2 diabetes in Indigenous communities in Canada. The objective of the study was to characterize dietary patterns using factor analysis (FA) and to relate these patterns to the incidence of type 2 diabetes after 10 years of follow up in a First Nations community in Ontario, Canada. METHODS: We conducted a prospective analysis of 492 participants in the SLHDP who did not have diabetes at baseline (1993 to 1995) and were followed for 10 years. A food-frequency questionnaire was administered, and FA was used to identify patterns of food consumption. Multivariate logistic regression analyses determined associations of food patterns with incident type 2 diabetes, adjusting for sociodemographic and lifestyle confounders. RESULTS: At follow up, 86 participants had developed incident type 2 diabetes. FA revealed 3 prominent dietary patterns: Balanced Market Foods, Beef and Processed Foods and Traditional Foods. After adjustment for age, sex, waist circumference, interleukin-6 and adiponectin, the Beef and Processed Foods pattern was associated with increased risk for incident type 2 diabetes (OR=1.38; 95% CI 1.02, 1.86). In contrast, the Balanced Market Foods and Traditional Foods Patterns were not significantly associated with type 2 diabetes. CONCLUSIONS: Dietary interventions should encourage reduced consumption of unhealthful market foods, in combination with improvements in local food environments so as to increase access to healthful foods and reduce food insecurity in Indigenous communities. PMID- 27374253 TI - Ultrasound-guided vessel catheterization in adult Yorkshire cross-bred pigs. AB - OBJECTIVE: To describe an ultrasound-guided approach for venous and arterial vascular access and catheterization in anesthetized adult Yorkshire cross-bred pigs. STUDY DESIGN: Prospective experimental study. ANIMALS: Ten adult female Yorkshire cross-bred pigs, weighing 78.4 +/- 5.6 kg (mean +/- standard deviation). METHODS: Using ultrasound guidance and the Seldinger technique, a 7 Fr, 20 cm triple-lumen central venous catheter was placed in the external jugular vein and an 18 gauge, 16 cm catheter was placed in the femoral artery. The success rate of catheterization and the incidence of catheter patency over 24 hours of general anesthesia were recorded. RESULTS: Catheterization of the external jugular vein was successful in 10 out of 10 pigs and catheterization of the femoral artery was successful in eight out of 10 pigs. A surgical dissection technique on the femoral artery was performed in two pigs. Venous and arterial catheter patency was maintained in all pigs over the 24 hour study period. CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasound guidance resulted in success rates of 100% for catheterization of the external jugular vein and 80% for catheterization of the femoral artery in anesthetized adult Yorkshire cross-bred pigs. This technique is a noninvasive, easily performed alternative to surgical exposure of the vessels in large pigs undergoing surgical instrumentation for biomedical device testing. PMID- 27374254 TI - Promoting the perception of two and three concurrent sound objects: An event related potential study. AB - The auditory environment typically comprises several simultaneously active sound sources. In contrast to the perceptual segregation of two concurrent sounds, the perception of three simultaneous sound objects has not yet been studied systematically. We conducted two experiments in which participants were presented with complex sounds containing sound segregation cues (mistuning, onset asynchrony, differences in frequency or amplitude modulation or in sound location), which were set up to promote the perceptual organization of the tonal elements into one, two, or three concurrent sounds. In Experiment 1, listeners indicated whether they heard one, two, or three concurrent sounds. In Experiment 2, participants watched a silent subtitled movie while EEG was recorded to extract the object-related negativity (ORN) component of the event-related potential. Listeners predominantly reported hearing two sounds when the segregation promoting manipulations were applied to the same tonal element. When two different tonal elements received manipulations promoting them to be heard as separate auditory objects, participants reported hearing two and three concurrent sounds objects with equal probability. The ORN was elicited in most conditions; sounds that included the amplitude- or the frequency-modulation cue generated the smallest ORN amplitudes. Manipulating two different tonal elements yielded numerically and often significantly smaller ORNs than the sum of the ORNs elicited when the same cues were applied on a single tonal element. These results suggest that ORN reflects the presence of multiple concurrent sounds, but not their number. The ORN results are compatible with the horse-race principle of combining different cues of concurrent sound segregation. PMID- 27374255 TI - Goal striving strategies and effort mobilization: When implementation intentions reduce effort-related cardiac activity during task performance. AB - Two experiments investigate the influence of goal and implementation intentions on effort mobilization during task performance. Although numerous studies have demonstrated the beneficial effects of setting goals and making plans on performance, the effects of goals and plans on effort-related cardiac activity and especially the cardiac preejection period (PEP) during goal striving have not yet been addressed. According to the Motivational Intensity Theory, participants should increase effort mobilization proportionally to task difficulty as long as success is possible and justified. Forming goals and making plans should allow for reduced effort mobilization when participants perform an easy task. However, when the task is difficult, goals and plans should differ in their effect on effort mobilization. Participants who set goals should disengage, whereas participants who made if-then plans should stay in the field showing high effort mobilization during task performance. As expected, using an easy task in Experiment 1, we observed a lower cardiac PEP in both the implementation intention and the goal intention condition than in the control condition. In Experiment 2, we varied task difficulty and demonstrated that while participants with a mere goal intention disengaged from difficult tasks, participants with an implementation intention increased effort mobilization proportionally with task difficulty. These findings demonstrate the influence of goal striving strategies (i.e., mere goals vs. if-then plans) on effort mobilization during task performance. PMID- 27374256 TI - Managing a Mass CO Poisoning: Critical Issues and Solutions From the Field to the Hyperbaric Chamber. AB - Carbon monoxide acute intoxication is a common cause of accidental poisoning in industrialized countries and sometimes it produces a real mass casualty incident. The incident described here occurred in a church in the province of Verona, when a group of people was exposed to carbon monoxide due to a heating system malfunction. Fifty-seven people went to the Emergency Department. The mean carboxyhemoglobin (COHb) level was 10.1+/-5.7% (range: 3-25%). The clinicians, after medical examination, decided to move 37 patients to hyperbaric chambers for hyperbaric oxygen (HBO) therapy. This is the first case report that highlights and analyses the logistic difficulties of managing a mass carbon monoxide poisoning in different health care settings, with a high influx of patients in an Emergency Department and a complex liaison between emergency services. This article shows how it is possible to manage a complex situation with good outcome. (Disaster Med Public Health Preparedness. 2017;11:251-255). PMID- 27374257 TI - Unexpected biodiversity of ciliates in marine samples from below the photic zone. AB - Marine microbial eukaryotes play critical roles in planktonic food webs and have been described as most diverse in the photic zone where productivity is high. We used high-throughput sequencing (HTS) to analyse the spatial distribution of planktonic ciliate diversity from shallow waters (<30 m depth) to beyond the continental shelf (>800 m depth) along a 163 km transect off the coast of New England, USA. We focus on ciliates in the subclasses Oligotrichia and Choreotrichia (class Spirotrichea), as these taxa are major components of marine food webs. We did not observe the decrease of diversity below the photic zone expected based on productivity and previous analyses. Instead, we saw an increase of diversity with depth. We also observed that the ciliate communities assessed by HTS cluster by depth layer and degree of water column stratification, suggesting that community assembly is driven by environmental factors. Across our samples, abundant OTUs tend to match previously characterized morphospecies while rare OTUs are more often undescribed, consistent with the idea that species in the rare biosphere remain to be characterized by microscopy. Finally, samples taken below the photic zone also reveal the prevalence of two uncharacterized (i.e. lacking sequenced morphospecies) clades - clusters X1 and X2 - that are enriched within the nano-sized fraction (2-10 MUm) and are defined by deletions within the region of the SSU-rDNA analysed here. Together, these data reinforce that we still have much to learn about microbial diversity in marine ecosystems, especially in deep-waters that may be a reservoir for rare species and uncharacterized taxa. PMID- 27374259 TI - Switching enhancer methylation in metastatic melanoma. PMID- 27374258 TI - Sharp temporal tuning in the bat auditory midbrain overcomes spectral-temporal trade-off imposed by cochlear mechanics. AB - In the cochlea of the mustached bat, cochlear resonance produces extremely sharp frequency tuning to the dominant frequency of the echolocation calls, around 61 kHz. Such high frequency resolution in the cochlea is accomplished at the expense of losing temporal resolution because of cochlear ringing, an effect that is observable not only in the cochlea but also in the cochlear nucleus. In the midbrain, the duration of sounds is thought to be analyzed by duration-tuned neurons, which are selective to both stimulus duration and frequency. We recorded from 57 DTNs in the auditory midbrain of the mustached bat to assess if a spectral-temporal trade-off is present. Such spectral-temporal trade-off is known to occur as sharp tuning in the frequency domain which results in poorer resolution in the time domain, and vice versa. We found that a specialized sub population of midbrain DTNs tuned to the bat's mechanical cochlear resonance frequency escape the cochlear spectral-temporal trade-off. We also show evidence that points towards an underlying neuronal inhibition that appears to be specific only at the resonance frequency. PMID- 27374261 TI - [Spontaneous pneumomediastinum indicative of dermatomyositis]. PMID- 27374260 TI - [Relapsing polychondritis with meningitis: Focus on a case report demonstrating remission under immunosuppressive agents]. PMID- 27374262 TI - [Emergency percutaneous valvuloplasty: Which patients, which results?] AB - Balloon aortic valvuloplasty is a relatively simple procedure with a low rate of complications despite patients' frailty. Urgent balloon aortic valvuloplasty is especially useful in patients with temporary contra-indication to TAVI or in case of difficult clinical scenario. It allows for a functional improvement for up to 6 months. This period should be used to bridge the patient to TAVI or surgical aortic valve replacement, stand-alone aortic valvuloplasty being without mid-term survival benefit. PMID- 27374263 TI - Diagnostic procedure after an immediate hypersensitivity reaction in the operating room. AB - The diagnosis of a perioperative allergic reaction is based on clinical features associated with a suggestive timeline, the exclusion of other diagnoses, elevated concentrations of degranulation markers (histamine, tryptase), and positive allergy assessments (skin tests, specific IgE). After initiating appropriate treatment, the anesthesiologist should take blood samples to measure histamine and tryptase concentrations just after the reaction and repeat them 1-2hours later to validate the diagnosis of immediate hypersensitivity. A delayed measurement of basal tryptase is useful to rule out mastocytosis and to interpret moderate tryptase levels. The anesthesiologist must inform the patient of the reaction to obtain adhesion and consent to subsequent investigations and must record the timing of the reaction and of the blood sampling, the possible causal agents, and the treatment administered. These data must be shared with the laboratory and the allergist. An adverse drug reaction report must be filed. The gold standard for allergy assessment is skin testing. These tests should be done in an appropriate facility, with experienced staff and in compliance with current guidelines. Specific IgE assays and cellular assays can help when clinical features and skin tests are discordant. Provocation tests are sometimes required. After allergy assessment, the safest protocol for subsequent anesthesia is determined in collaboration with the anesthesiologist. The patient must be informed and carry an allergy alert card. PMID- 27374264 TI - What does acute onset means in the context of Staphylococcus aureus infective endocarditis? Description of a hyperacute infective endocarditis. PMID- 27374265 TI - [2015 ESC guidelines: 1-hour rule-out and rule-in of acute myocardial infarction with high-sensitive troponin T]. AB - High sensitivity cardiac troponins must be used in first intention. H0/H3 algorithm is recommended in the diagnostic strategy. In total, 75% of emergency patients can be early discharged with the H0/H1 algorithm. Interpretation of troponin values requires taking into account the clinical context and electrocardiogram. The algorithm H0/H1 cannot be used for early presenters in ED after onset of chest pain. Further validation studies are needed before widespread application of H0/H1 algorithm. PMID- 27374266 TI - [Management of hyperglycemic/diabetic patient during and in the immediate follow up of an acute coronary syndrome]. AB - Two thirds of the patients hospitalized for an acute coronary syndrome (ACS) show disorders of glucose metabolism (diabetes, impaired fasting glucose, impaired glucose intolerance). Every patient hospitalized for an ACS whose HbA1c is equal or above 6.5% must be considered as diabetic. Each patient hospitalized for an ACS whose HbA1c is less than 6.5% should have measurement of plasma glucose fasting and after an oral glucose load between the 7th and the 28th day following the ACS in order to detect a disorder of glucose metabolism. During the hospitalization in cardiac intensive care unit, a treatment with insulin will be started when plasma glucose is>=1.80g/L (10.0mmol/L). In a patient with previously known diabetes, a treatment with insulin will also be started when preprandial plasma glucose is 1.40g/L (7.8mmol/L). Insulin treatment in cardiac intensive care unit will be performed by continuous IV infusion of insulin including bolus for meals. Insulin dosage will be determined according to the capillary glucose monitoring. After the hospitalization in cardiac intensive care unit, it is often possible to stop insulin treatment, which may be replaced by other antidiabetic treatments. The choice of the optimal antidiabetic treatment depends on the metabolic profile of the patient (insulin-resistance, insulin deficiency). This choice is not always easy and referral to an endocrinologist/diabetolgist may be needed. Because of the increased cardiovascular mortality associated with hypoglycemias, the long-term use of insulin or insulin-secretory agents (sulfonylureas, glinides) must be limited. During and in the immediate follow-up of an ACS, referral to an endocrinologist/diabetologist is recommended in case of diagnosis of diabetes, when HbA1c>=8%, when long-term treatment with insulin has been initiated and in case of frequent or severe hypoglycemias. PMID- 27374267 TI - HyperCKemia induced by levetiracetam. PMID- 27374268 TI - Obesity in Botswana: time for new cut-off points for abdominal girth? AB - INTRODUCTION: Country-specific cut-off points for defining central obesity in black Africans are long overdue. METHODS: Anthropometric data from 215 (51.4%) male and 203 (48.6%) female patients seen in Gaborone between 2005 and 2015 were analysed to establish appropriate cut-off points for waist circumference (WC) corresponding to a body mass index (BMI) of 30 kg/m2. Relative risks for cardiometabolic disorders were calculated for different BMI and WC categories using MedCalc(r). The subjects' mean age was 50.0 +/- 10.8 years and 80.6% were Batswana. RESULTS: Only 7.2% of patients had a BMI < 25 kg/m2, 27.3% were overweight and 65.5% were obese; mean BMI was 34.9 +/- 6.5 kg/m2 in the women versus 31.0 +/- 4.9 kg/m2 in the men (p < 0.0001). New cut-off points of 98 cm in men and 85 cm in women emerged. Different weight and WC categories appeared not to confer increased relative risk of hypertension, dysglycaemia or dyslipidaemia. CONCLUSION: The proposed WC cut-off values, if validated, should set the pace for larger studies across sub-Saharan Africa. PMID- 27374270 TI - Host-guest chemistry that directly targets lysine methylation: synthetic host molecules as alternatives to bio-reagents. AB - Post-translational methylation is a chemically simple modification, but regulates the function of hundreds of proteins in profound ways. This Feature Article will report on the basic aspects of protein methylation, and will offer a personal perspective on our recent efforts at making supramolecular hosts that can bind and discriminate among post-translationally methylated partners. The article highlights several general lessons drawn from these efforts and related work by other groups. It also describes some ways in which supramolecular approaches are inherently well suited to provide tools that drive new research in the life sciences. PMID- 27374271 TI - Interactions of Dietary Fats and Proteins on Fatty Acid Composition of Immune Cells and LTB4 Production by Peritoneal Exudate Cells of Rats. AB - The interaction of dietary fats and proteins on lipid parameters of rats was studied using safflower oil (linoleic acid-rich), borage oil (gamma-linolenic acid-rich) or perilla oil (alpha-linolenic acid-rich) in combination with casein or soybean protein. The experiment was focused on the fatty acid composition of immune cells and the leukotriene B4 production by peritoneal exudate cells. Serum total cholesterol, triglyceride, and phospholipid levels were low in perilla oil fed or soybean protein-fed rats. Fatty acid compositions of serum and liver phospholipids reflected those of dietary fats. However, feeding borage oil resulted in a marked increase in the proportion of dihomo-gamma-linolenic acid in phospholipids of peritoneal exudate cells, spleen lymphocytes, and mesenteric lymph node lymphocytes in relation to those of liver and serum. It is suggested that activities of metabolic n-6 polyunsaturated fatty acids are different between immune and other tissues. In addition, the magnitude of the reduction of the proportion of linoleic acid of perilla oil in immune cells was considerably more moderate than serum and liver, indicating a different degree of interference of alpha-linolenic acid with linoleic acid metabolism. Leukotriene B4 release from peritoneal exudate cells was in the order of safflower oil>borage oil>perilla oil groups as reflecting the proportion of arachidonic acid, and tended to be lower in soybean protein-fed groups. These suggest an anti inflammatory property of gamma-linolenic acid as well as alpha-linolenic acid tended to be strengthened when they were combined with soybean protein than with casein. PMID- 27374273 TI - The Cancer Communication Assessment Tool for Patients and Families (CCAT-PF): a new measure. PMID- 27374272 TI - The amino acid-rich elemental diet Elental(r) preserves lean body mass during chemo- or chemoradiotherapy for esophageal cancer. AB - Chemo (chemoradio) therapy can induce oral mucositis and change body composition in patients with esophageal cancer. The impact of the amino acid-rich elemental diet Elental(r) on oral mucositis and changes in body composition during chemo (chemoradio) therapy is unclear. Thus, the purpose of the present study was to examine the preventive effects of Elental on oral mucositis and sarcopenia progression during chemo (chemoradio) therapy for esophageal cancer. Patients were randomized to receive either azulene oral rinse (Arm 1) or Elental (Arm 2) during the treatment cycle (4 weeks). The incidence of oral mucositis and other adverse events was evaluated weekly. Body composition pre- and post-treatment cycle was measured by bioelectric impedance analysis. Thirty-three patients (17 azulene and 16 Elental) completed the study, and the groups were well matched. Elental tended to reduce the incidence of oral mucositis (Arm 1, 23.5% and Arm 2, 12.5%), but there was no statistically significant difference between the groups. The average body mass index (BMI) and body fat mass decreased significantly in both groups after the treatments. Lean body mass (LBM) was reduced in Arm 1, but was increased in Arm 2 after the treatment; the relative change of LBM after the treatment was significant between Arm 1 and Arm 2 (P=0.007). This study revealed that Elental nutrition could counteract sarcopenia development during chemoradiotherapy for esophageal cancer. These properties may lead to improvement of the quality of life and clinical outcome of esophageal cancer patients treated with chemo (chemoradio) therapy (Clinical Trial Registry ID: UMIN 000007960). PMID- 27374274 TI - Safety and tolerability of bosentan for digital ulcers in Japanese patients with systemic sclerosis: Prospective, multicenter, open-label study. AB - A multicenter, open-label study was performed to investigate the safety and tolerability of bosentan in Japanese patients with systemic sclerosis (SSc) and secondary digital ulcers. Twenty-eight patients were enrolled. The safety and tolerability of bosentan was monitored over 52 weeks of study treatment (primary end-point), while incidence and healing of digital ulcers were also assessed up to week 16. The following adverse events occurred in 5% or more of patients during the 52-week treatment period: upper respiratory tract infection (50.0%), abnormal liver function tests (42.9%), digital ulcers (25.0%), anemia (17.9%), peripheral edema (14.3%), diarrhea (10.7%), urinary tract infection (7.1%), arthralgia (7.1%), constipation (7.1%) and herpes zoster (7.1%). Eight patients experienced at least one serious adverse event, including drug-related serious adverse events in two patients, which were abnormal liver function tests and fluid retention (pericardial effusion) in one patient each. During the 16-week observation period, seven out of 28 patients (25%) developed new digital ulcers. In this study, adverse events were comparable with those previously reported with bosentan. Approximately half of the patients had adverse events associated with abnormal liver function tests, thus we conclude that liver function should be monitored regularly during treatment with bosentan. PMID- 27374275 TI - Role of the yeast ribosomal protein L16 in ribosome biogenesis. AB - Most ribosomal proteins play essential roles in ribosome synthesis and function. In this study, we have analysed the contribution of yeast ribosomal protein L16 to ribosome biogenesis. We show that in vivo depletion of the essential L16 protein results in a deficit in 60S subunits and the appearance of half-mer polysomes. This phenotype is likely due to the instability and rapid turnover of early and intermediate pre-60S particles, as evidenced by the reduced steady state levels of 27SBS and 7SL /S pre-rRNA, and the low amounts of de novo synthesized 27S pre-rRNA and 25S rRNA. Additionally, depletion of L16 blocks nucleocytoplasmic export of pre-60S particles. Moreover, we show that L16 assembles in the nucleolus and binds to early 90S preribosomal particles. Many evolutionarily conserved ribosomal proteins possess extra eukaryote-specific amino- or carboxy-terminal extensions and/or internal loops. Here, we have also investigated the role of the eukaryote-specific carboxy-terminal extension of L16. Progressive truncation of this extension recapitulates, albeit to a lesser extent, the growth and ribosome biogenesis defects of the L16 depletion. We conclude that L16 assembly is a prerequisite to properly stabilize rRNA structures within early pre-60S particles, thereby favouring efficient 27S pre rRNA processing within the internal transcribed spacer 1 at sites A3 and B1 . Upon depletion of L16, the lack of this stabilization aborts early pre-60S particle assembly and subjects these intermediates to turnover. PMID- 27374276 TI - Bioavailability and Chemical/Functional Aspects of Synthetic MK-7 vs Fermentation Derived MK-7 in Randomised Controlled Trials. AB - We investigated the bioavailability of a synthetic form of the vitamin K2 molecule menaquinone-7 (MK-7) in a randomised single-blinded two-way cross-over study. Healthy subjects (20 - 66 years of age) took a single 180 MUg dose of synthetic MK-7 or fermentation-derived MK-7, and serum MK-7 concentrations were monitored for 72 hours to calculate AUC(0 - 72 h) and Cmax. We also compared the biological effects of placebo, fermentation-derived MK-7 (90 MUg) and 3 doses of synthetic MK-7(45, 90 and 180 MUg) in a randomised double-blinded parallel study. Healthy subjects (20 - 60 years of age) took one of the supplements daily for 43 days, and the fraction of carboxylated osteocalcin (OC) was compared between day 1 and day 43 as a marker for vitamin K activity. In the bioavailability study, the 90 % confidence interval for the ratio of the AUC(0-72 h) values for synthetic and fermentationderived MK-7 was 83 - 111, indicating bioequivalence. The 90 % confidence interval for the Cmax ratio was 83 - 131. The serum concentrations of carboxylated OC and undercarboxylated OC were increased (p = 0.01) and reduced (p = 0.02), respectively, after daily intake of 180 MUg of synthetic MK-7 for 43 days, indicating increased vitamin K activity. Across both studies, only 1 participant reported an adverse event (dry mouth; 180 MUg synthetic MK-7 group, functional study) that was considered possibly related to synthetic MK-7 supplementation. Our findings provide evidence that the tested synthetic form of MK-7 is bioequivalent to fermentation-derived MK-7, exhibits vitamin K activity and is well tolerated in healthy subjects. PMID- 27374279 TI - Sebaceous lymphadenoma of the thymus: A clinicopathologic and immunohistochemical study of 2 cases. AB - Two cases of primary sebaceous lymphadenoma of the thymus are presented. The patients were a man and a woman 58 and 77 years old, respectively. The female patient had a history of breast carcinoma and on follow-up was identified to have an anterior mediastinal mass; the male patient did not have any history of malignancy, and the tumor was discovered during a chest radiographic evaluation when the patient presented with symptoms of fatigue, chest pain, and dyspnea. Histologically, both lesions were characterized by the presence of solid-cystic epithelial islands in a prominent lymphocytic background. The epithelial islands were haphazardly distributed in the form of small tubular structures with focal keratinization and groups of epithelial cells with clear cytoplasm, round nuclei and lack of mitotic activity in keeping with sebaceous cells. The presence of germinal centers in the lymphoid background was seen in both cases. Immunohistochemically, the epithelial component was positive for cytokeratin 8 (CAM5.2), cytokeratin 5/6, and for adipophilin in the sebaceous component. B- and T-cell markers were positive in the lymphoid component. Clinical follow-up in both patients showed that the 2 patients were well and alive 3 years after diagnosis. The cases herein presented expand the spectrum of salivary gland-type tumors in the mediastinum and raise awareness of lesions which are easily confused with other more common thymic tumors that have different prognosis and treatment implications. PMID- 27374278 TI - Mobilization of Medial and Lateral Frontal-Striatal Circuits in Cocaine Users and Controls: An Interleaved TMS/BOLD Functional Connectivity Study. AB - The integrity of frontal-striatal circuits is an area of great interest in substance dependence literature, particularly as the field begins to develop neural circuit-specific brain stimulation treatments for these individuals. Prior research indicates that frontal-striatal connectivity is disrupted in chronic cocaine users in a baseline (resting) state. It is unclear, however, if this is also true when these circuits are mobilized by an external source. In this study, we measured the functional and structural integrity of frontal-striatal circuitry involved in limbic arousal and executive control in 36 individuals-18 cocaine dependent individuals with a history of failed quit attempts and 18 age-matched controls. This was achieved by applying a transcranial magnetic stimulation to the medial prefrontal cortex (Brodmann area 10) and the dorsolateral prefrontal cortex (lateral Brodmann 9) while participants rested in the MRI scanner (TMS/BOLD imaging). Relative to the controls, cocaine users had a lower ventral striatal BOLD response to MPFC stimulation. The dorsal striatal BOLD response to DLPFC stimulation however was not significantly different between the groups. Among controls, DLPFC stimulation led to a reciprocal attenuation of MPFC activity (BA 10), but this pattern did not exist in cocaine users. No relationship was found between regional diffusion metrics and functional activity. Considered together these data suggest that, when engaged, cocaine users can mobilize their executive control system similar to controls, but that the 'set point' for mobilizing their limbic arousal system has been elevated-an interpretation consistent with opponent process theories of addiction. PMID- 27374277 TI - Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [11C](+)PHNO. AB - Most prior work with positron emission tomography (PET) dopamine subtype 2/3 receptor (D2/3R) non-selective antagonist tracers suggests that obese (OB) individuals exhibit lower D2/3Rs when compared with normal weight (NW) individuals. A D3-preferring D2/3R agonist tracer, [11C](+)PHNO, has demonstrated that body mass index (BMI) was positively associated with D2/3R availability within striatal reward regions. To date, OB individuals have not been studied with [11C](+)PHNO. We assessed D2/3R availability in striatal and extrastriatal reward regions in 14 OB and 14 age- and gender-matched NW individuals with [11C](+)PHNO PET utilizing a high-resolution research tomograph. Additionally, in regions where group D2/3R differences were observed, secondary analyses of 42 individuals that constituted an overweight cohort was done to study the linear association between BMI and D2/3R availability in those respective regions. A group-by-brain region interaction effect (F7, 182=2.08, p=0.047) was observed. Post hoc analyses revealed that OB individuals exhibited higher tracer binding in D3-rich regions: the substantia nigra/ventral tegmental area (SN/VTA) (+20%; p=0.02), ventral striatum (VST) (+14%; p<0.01), and pallidum (+11%; p=0.02). BMI was also positively associated with D2/3R availability in the SN/VTA (r=0.34, p=0.03), VST (r=0.36, p=0.02), and pallidum (r=0.30, p=0.05) across all subjects. These data suggest that individuals who are obese have higher D2/3R availability in brain reward regions densely populated with D3Rs, potentially identifying a novel pharmacologic target for the treatment of obesity. PMID- 27374280 TI - Descending Necrotizing Mediastinitis Secondary to Spontaneous Sternocleidomastoid Muscle Abscess. PMID- 27374281 TI - Pros and Cons of Telemedicine in the Management of Patients with Chronic Respiratory Diseases. PMID- 27374282 TI - Frequent or Persistent Exacerbations: Identifying The Real Problem. PMID- 27374283 TI - Changes in ABCB1 mRNA Expression in Peripheral Blood Cells before and after Renal Transplantation. AB - Cyclosporine (CSA), which is one of the substrates of ATP binding cassette subfamily B member 1 (ABCB1), is widely used as an immunosuppressant in patients undergoing transplantation. The expression level of P-glycoprotein on lymphocytes that is encoded by ABCB1 gene is considered to be one of the major causes of differences in intracellular CSA concentration. The clinical relevance of ABCB1 mRNA expression in peripheral blood was analyzed. We examined (i) the relationship between ABCB1 mRNA and the intracellular concentration of CSA in vitro, (ii) the change in long-term ABCB1 mRNA expression levels, and (iii) its association with acute rejection (AR) or cytomegalovirus (CMV) reactivation in living-donor renal transplantation. A significantly negative correlation between ABCB1 mRNA expression and intracellular CSA concentration in vitro was obtained (p<0.05). ABCB1 mRNA expression was significantly reduced (55%) 1 week after transplantation (p<0.001) and returned to the pre-transplantation level after 1 year. Although the sample size may be too small to obtain a definitive conclusion, no association was observed between ABCB1 mRNA expression levels and AR or CMV reactivation. PMID- 27374284 TI - Interferon-gamma Attenuates 5-Hydroxytryptamine-Induced Melanogenesis in Primary Melanocyte. AB - Interferon-gamma (IFN-gamma) is an important cytokine which can be secreted by keratinocytes or macrophages induced by UVB irradiation in skin. Mammalian skin cells have the capability to produce and metabolize 5-hydroxytryptamine (5-HT) whose cutaneous effects are mediated by the interactions with 5-HT receptors. Treatment with 5-HT resulted in a dose-dependent increase of tyrosinase (TYR) activity and melanin contents in normal human foreskin-derived epidermal melanocytes (NHEM), while with IFN-gamma a decreased effect resulted. These regulatory results were due to changes of the expression levels of microphthalmia associated transcription factor (MITF) and its downstream TYR, tyrosinase-related protein 1 (TRP-1) and dopachrome tautomerase (DCT). We proved here that 5 HTR1A/2A participated in the regulation of melanogenesis. IFN-gamma could offset the pro-melanogenesis effect of 5-HT in NHEM and the intensity of this neutralization was unanticipated below the baseline level. IFN-gamma neutralized the up-regulation effect of 5-HT on MITF and downstream TYR, TRP-1 and DCT. Though functioning as 5-HT1A/2A receptor during the melanogenesis process, IFN gamma played no role in 5-HT1A/2A receptor expressions. Our results also demonstrated that the inhibition of IFN-gamma was reversible after its removal. Confusingly, the effect of cross-talk between 5-HT and IFN-gamma on NHEM melanogenesis was irreversible. Whether treated with 5-HT for 5 d or 12 d, the pigmentation level neither recovered after displacing the IFN-gamma-containing medium. In addition, IFN-gamma was able to inhibit the inductive effect of 5-HT on NHEM migration. Taken together, the suppression of IFN-gamma on 5-HT-induced melanogenesis further suggests the negative role of IFN-gamma in inflammation associated pigmentary changes. PMID- 27374285 TI - Astrocytes Release Polyunsaturated Fatty Acids by Lipopolysaccharide Stimuli. AB - We previously reported that levels of long-chain fatty acids (FAs) including docosahexaenoic acids (DHA) increase in the hypothalamus of inflammatory pain model mice. However, the precise mechanisms underlying the increment of free fatty acids (FFAs) in the brain during inflammation remains unknown. In this study, we characterized FFAs released by inflammatory stimulation in rat primary cultured astrocytes, and tested the involvement of phospholipase A2 (PLA2) on these mechanisms. Lipopolysaccharide (LPS) stimulation significantly increased the levels of several FAs in the astrocytes. Under these conditions, mRNA expression of cytosolic PLA2 (cPLA2) and calcium-independent PLA2 (iPLA2) in LPS treated group increased compared with the control group. Furthermore, in the culture media, the levels of DHA and arachidonic acid (ARA) significantly increased by LPS stimuli compared with those of a vehicle-treated control group whereas the levels of saturated FAs (SFAs), namely palmitic acid (PAM) and stearic acid (STA), did not change. In summary, our findings suggest that astrocytes specifically release DHA and ARA by inflammatory conditions. Therefore astrocytes might function as a regulatory factor of DHA and ARA in the brain. PMID- 27374286 TI - Ginger Orally Disintegrating Tablets to Improve Swallowing in Older People. AB - We previously prepared and pharmaceutically evaluated ginger orally disintegrating (OD) tablets, optimized the base formulation, and carried out a clinical trial in healthy adults in their 20 s and 50s to measure their effect on salivary substance P (SP) level and improved swallowing function. In this study, we conducted clinical trials using the ginger OD tablets in older people to clinically evaluate the improvements in swallowing function resulting from the functional components of the tablet. The ginger OD tablets were prepared by mixing the excipients with the same amount of mannitol and sucrose to a concentration of 1% ginger. Eighteen healthy older adult volunteers aged 63 to 90 were included in the swallowing function test. Saliva was collected before and 15 min after administration of the placebo and ginger OD tablets. Swallowing endoscopy was performed by an otolaryngologist before administration and 15 min after administration of the ginger OD tablets. A scoring method was used to evaluate the endoscopic swallowing. Fifteen minutes after taking the ginger OD tablets, the salivary SP amount was significantly higher than prior to ingestion or after taking the placebo (p<0.05). Among 10 subjects, one scored 1-3 using the four evaluation criteria. Overall, no aspiration occurred and a significant improvement in the swallowing function score was observed (p<0.05) after taking the ginger OD tablets. Our findings showed that the ginger OD tablets increased the salivary SP amount and improved swallowing function in older people with appreciably reduced swallowing function. PMID- 27374287 TI - Corticosterone Inhibits the Proliferation of C6 Glioma Cells via the Translocation of Unphosphorylated Glucocorticoid Receptor. AB - Astroglial cells have been considered to have passive brain function by helping to maintain neurons. However, recent studies have revealed that the dysfunction of such passive functions may be associated with various neuropathological diseases, such as schizophrenia, Alzheimer's disease, amyotrophic lateral sclerosis and major depression. Corticosterone (CORT), which is often referred to as the stress hormone, is a well-known regulator of peripheral immune responses and also shows anti-inflammatory properties in the brain. However, it is still obscure how CORT affects astroglial cell function. In this study, we investigated the effects of CORT on the proliferation and survival of astroglial cells using C6 glioma cells. Under treatment with CORT for 24h, the proliferation of C6 glioma cells decreased in a dose-dependent manner. Moreover, this inhibition was diminised by treatment with mifepristone, a glucocorticoid receptor (GR) antagonist, but not by spironolactone, a mineralocorticoid receptor (MR) antagonist, and was independent of GR phosphorylation and other GR-related intracellular signaling cascades. Furthermore, it was observed that the translocation of GR from the cytosol to the nucleus was promoted by the treatment with CORT. These results indicate that CORT decreases the proliferation of C6 glioma cells by modifying the transcription of a particular gene related to cell proliferation independent of GR phosphorylation. PMID- 27374288 TI - Cinnamomum loureirii Extract Inhibits Acetylcholinesterase Activity and Ameliorates Trimethyltin-Induced Cognitive Dysfunction in Mice. AB - The pathogenesis of Alzheimer's disease (AD) has been linked to the deficiency of neurotransmitter acetylcholine (ACh) in the brain, and the main treatment strategy for improving AD symptoms is the inhibition of acetylcholinesterase (AChE) activity. In the present study, we aimed to identify potent AChE inhibitors from Cinnamomum loureirii extract via bioassay-guided fractionation. We demonstrated that the most potent AChE inhibitor present in the C. loureirii extract was 2,4-bis(1,1-dimethylethyl)phenol. To confirm the antiamnesic effects of the ethanol extract of C. loureirii, mice were intraperitoneally injected with the neurotoxin trimethyltin (2.5 mg/kg) to induce cognitive dysfunction, and performance in the Y-maze and passive avoidance tests was assessed. Treatment with C. loureirii extract significantly improved performance in both behavioral tests, suggesting that this extract may be neuroprotective and therefore beneficial in preventing or ameliorating the degenerative processes of AD, potentially by restoring cholinergic function. PMID- 27374289 TI - Gallic Acid, the Active Ingredient of Terminalia bellirica, Enhances Adipocyte Differentiation and Adiponectin Secretion. AB - Visceral obesity induces the onset of metabolic disorders such as insulin resistance and diabetes mellitus. Adipose tissue is considered as a potential pharmacological target for treating metabolic disorders. The fruit of Terminalia bellirica is extensively used in Ayurvedic medicine to treat patients with diseases such as diabetes mellitus. We previously investigated the effects of a hot water extract of T. bellirica fruit (TB) on obesity and insulin resistance in spontaneously obese type 2 diabetic mice. To determine the active ingredients of TB and their molecular mechanisms, we focused on adipocyte differentiation using mouse 3T3-L1 cells, which are widely used to study adipocyte physiology. We show here that TB enhanced the differentiation of 3T3-L1 cells to mature adipocytes and that one of the active main components was identified as gallic acid. Gallic acid (10-30 uM) enhanced the expression and secretion of adiponectin via adipocyte differentiation and also that of fatty acid binding protein-4, which is the target of peroxisome proliferator-activated receptor gamma (PPARgamma), although it does not alter the expression of the upstream genes PPARgamma and CCAAT enhancer binding protein alpha. In the PPARgamma ligand assay, the binding of gallic acid to PPARgamma was undetectable. These findings indicate that gallic acid mediates the therapeutic effects of TB on metabolic disorders by regulating adipocyte differentiation. Therefore, TB shows promise as a candidate for preventing and treating patients with metabolic syndrome. PMID- 27374291 TI - Muscarinic Receptor Binding in Rat Bladder Urothelium and Detrusor Muscle by Intravesical Solifenacin. AB - Solifenacin is an antimuscarinic agent used to treat symptoms of overactive bladder. Pharmacologically significant amounts of solifenacin were excreted in the urine of humans taking a clinical dose of this drug. The aim of this study is to measure muscarinic receptor binding in the bladder urothelium and detrusor muscles of rats following the intravesical instillation of solifenacin. Muscarinic receptors were measured by radioreceptor assay using [N-methyl (3)H]scopolamine methyl chloride ([(3)H]NMS), a selective radioligand of muscarinic receptors. Solifenacin showed concentration-dependent inhibition of specific [(3)H]NMS binding in the bladder urothelium and detrusor muscle of rats, with no significant difference in Ki values or Hill coefficients between these tissues. Following the intravesical instillation of solifenacin, there was significant muscarinic receptor binding (increase in Kd for specific [(3)H]NMS binding) in the bladder urothelium and detrusor muscle of rats. Similar bladder muscarinic receptor binding was observed by the intravesical instillation of oxybutynin, but not with trospium. In conclusion, the present study has demonstrated that solifenacin binds muscarinic receptors not only in the detrusor muscle but also in the bladder urothelium with high affinity. These bladder muscarinic receptors may be significantly affected by solifenacin excreted in the urine. PMID- 27374290 TI - Is Coenzyme Q10 Effective in Protection against Ulcerative Colitis? An Experimental Study in Rats. AB - Coenzyme Q10 (Co-Q10) is a vitamin-like supplement which appears to be safe, with minimal side effects and low drug interaction potential. Co-Q10 is used in the treatment of a variety of disorders related primarily to suboptimal cellular energy metabolism and oxidative injury. Studies supporting the efficacy of Co-Q10 appear most promising for a variety of diseases, including ulcerative colitis (UC). The present investigation aims to elucidate the possible protective effects of Co-Q10 against UC, as induced by the administration of iodoacetamide to adult male albino rats. In our study, Co-Q10 showed potent anti-oxidant and anti inflammatory activities through a significant increase in catalase activity and glutathione content. In addition, it significantly decreased myeloperoxidase activity, malondialdehyde content and nitrate/nitrite production. These results suggest that Co-Q10 protects against UC in rats via anti-oxidant and anti inflammatory potentials, and therefore seems promising for use in further clinical trials. PMID- 27374292 TI - Gender- and Age-Associated Differences in Serum Metabolite Profiles among Japanese Populations. AB - Serum metabolites can reflect the diffusion/export of biochemicals from various organs. They can serve as biomarkers related to diseases and therapeutic efficacy/toxicity. While studies in Caucasians suggested that subject gender and age can affect circulating metabolite profiles, the Japanese population has not been surveyed. Our objective was to delineate gender- and age-associated differences in serum metabolite profiles among Japanese populations. Using a mass spectrometry-based global metabolomics approach, 516 endogenous metabolites were detected in sera from Japanese individuals. The principal component analysis identified gender as the primary component, followed by age, suggesting that these two criteria were key contributors to variations in the dataset. Gender associated differences were observed in 31 and 25% of metabolites in the young (age 25-35) and old (ages 55-65) populations, respectively, in redox homeostasis, and in steroid and purine nucleotide metabolism pathways. Age-associated differences were observed in 24 and 23% of metabolites in men and women, respectively. No pathway was commonly highlighted. Thus, gender and age impact on metabolite profiles in the Japanese population. Our results provide useful information to explore biomarkers for clinical applications in the Japanese population and to assess the applicability of known biomarkers identified in other populations to the Japanese population. PMID- 27374293 TI - Analysis of Staphylococcal Toxins and Clinical Outcomes of Methicillin-Resistant Staphylococcus aureus Bacteremia. AB - It is well known that methicillin-resistant Staphylococcus aureus (MRSA) produces many virulence factors, such as hemolysins, leukocidins, proteases, enterotoxins, exfoliative toxins, and immune-modulatory factors. The aim of study was to identify staphylococcal pathogenicity that may affect the prognosis of patients with MRSA bacteremia. We obtained 149 MRSA strains from blood cultures between January 2009 and December 2014 in our institution. We collected information on patient characteristics, laboratory data, staphylococcal toxin genes, and susceptibility of the strain toward anti-MRSA agent and analyzed them as factors contributing to 30-d mortality. The "survival" and "dead" groups consisted of 103 and 46 patients, respectively. Multiple logistic regression analysis showed a four-fold increase in the risk of mortality in patients exhibiting isolated MRSA with staphylococcal enterotoxins (SEs) genes as well as toxic shock syndrome toxin-1 (TSST-1) genes [odds ratio: 3.89; 95% confidence interval: 1.20-12.60; p=0.024]. Kaplan-Meier analysis also showed significantly higher mortality in patient with isolated MRSA with SEs and TSST-1 genes. After adjusting for confounders, the coexistence of SEs and TSST-1 were independently associated with the 30-d mortality compared with treatment and susceptibility. The coexistence of superantigenic toxin genes greatly affects the clinical course and prognosis of patients with MRSA bacteremia. PMID- 27374294 TI - Analysis of Skin Permeability and Toxicological Properties of Amorphous Silica Particles. AB - Nanomaterials (NMs) are defined as those which have nanostructured components less than 100 nm in diameter. They are widely used in various fields such as medicine, cosmetics, and the food industry. However, the toxicological effects of NMs are less well understood than their applications. In particular, the skin is exposed to the environment at all times, so is easily influenced by NMs. In this study, we investigated the skin permeability and toxicological properties of well dispersed amorphous silica particles with diameters ranging from 70 to 1000 nm, to aid in the safe application of NMs. Amorphous silica particles of 70 nm in size (nSP70) penetrated the living epidermis, following pretreatment with acetone/diethyl ether to improve skin permeation. The application of unmodified nSP70, carboxyl group-modified nSP70, or amino group-modified nSP70 for long durations caused little skin irritation at the application site. Under the present experimental conditions, few adverse systemic effects were evident from blood tests and histopathologic examination. These results suggest that decreasing particle size increases the NMs skin permeability, but remarkably little corresponding skin irritation is observed. PMID- 27374295 TI - Effect of Combination of Low-Frequency Sonophoresis or Electroporation with Iontophoresis on the Mannitol Flux or Electroosmosis through Excised Skin. AB - In vitro permeation studies of mannitol were conducted across excised hairless mouse skin to determine and compare the enhancing effect of electroporation (EP) or sonophoresis (SP) combined with iontophoresis (IP) on the electroosmotic flow, and to analyze the enhancement mechanism of these combined methods. Mannitol flux was utilized as an index for the electroosmotic flow due to its low molecular weight and no electrorepulsion effect. The combination of SP and IP (SP/IP) resulted in an apparent increase of electroosmotic flow (no effect was sometimes observed by SP/IP), while that of EP and IP (EP/IP) had no synergistic enhancing effect on the electroosmosis. Next, the combined effect of tape-stripping (TS) and IP (TS/IP) was examined in a similar manner to clarify the difference between the SP/IP and EP/IP effects on electroosmosis. When the TS number increased from 0 to 3, the electroosmotic flow increased with the TS number. However, no further increase was observed when the TS number became more than 3, and the flow started to decrease when the TS number became 5. The electric charge of the skin surface was then measured after SP or TS application. When SP was applied, the skin surface charge became much more negative and the electroosmotic flow by SP/IP was markedly increased. Thus, an increase in the electroosmotic flow across the skin during IP application can be obtained not by EP and TS, but by SP. The combined use of SP and IP is a promising means for the enhanced skin delivery of non electrolyte drugs. PMID- 27374296 TI - Nephronectin Expression Is Up-Regulated by BMP-2. AB - Nephronectin (Npnt), known to be a ligand of integrin alpha8beta1, plays important roles in the development and function of various tissues, including those of the kidneys, liver, bones, and muscles. In previous studies, we showed that the expression of Npnt mRNA was regulated by various cytokines, including transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF alpha), and oncostatin M (OSM), and that over-expression of Npnt enhanced osteoblast differentiation. In this study, we found that bone morphogenic protein 2 (BMP-2), known as an osteogenesis inducing cytokine, strongly up-regulated the expression of Npnt mRNA in a murine skeletal muscle cell line (C2C12) via the BMP SMAD signaling pathway. PMID- 27374297 TI - Enhancement of Automaticity by Mechanical Stretch of the Isolated Guinea Pig Pulmonary Vein Myocardium. AB - The effects of mechanical stretch on the automaticity of the guinea pig isolated pulmonary vein preparations were studied in microelectrode experiments. The application of cumulative mechanical stretch to the preparations resulted in increases in the firing rate of spontaneous electrical activity in the myocardial layer. This effect was significantly inhibited by stretch-activated channel blockers such as gadolinium or streptomycin. These results suggest that acute mechanical stretch enhances the automaticity of the guinea pig pulmonary vein myocardium through the opening of the stretch-activated channels. PMID- 27374298 TI - Betamethasone, but Not Tacrolimus, Suppresses the Development of Th2 Cells Mediated by Langerhans Cell-Like Dendritic Cells. AB - It is well known that Langerhans cells (LCs) work as the primary orchestrators in the polarization of the immune milieu towards a T helper type 1 (Th1) or T helper type 2 (Th2) response. In this study, we investigated the effects of tacrolimus and betamethasone, each used as topical applications in atopic dermatitis (AD), on Th2 cell development mediated by LCs. LC-like dendritic cells (LDCs) were generated from mouse bone marrow cells and used as substitutes for LCs. Mice were primed with ovalbumin (OVA) peptide-pulsed LDCs, which had been treated with tacrolimus or betamethasone, via the hind footpad. After 5 d, the cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The expression of cell surface molecules on LDCs was investigated via reverse transcriptase polymerase chain reaction. Administration of OVA peptide-pulsed LDCs, which had been treated with betamethasone, inhibited Th2 cell development, as represented by the down-regulation of interleukin-4 production, and also inhibited Th1 cell development, represented by the down regulation of interferon-gamma production. However, tacrolimus-treated LDCs did not induce such inhibition of the development of Th1 and Th2 cells. The inhibition of Th1 and Th2 cell development was associated with the suppression of CD40 and T-cell immunoglobulin, and mucin domain-containing protein (TIM)-4 expression, respectively, in LDCs. These results suggest that the topical application of betamethasone to skin lesions of patients with AD acts on epidermal LCs, and may inhibit the development of Th2 cells, thus being of benefit for the control of AD. PMID- 27374299 TI - Gender differences in the saliva of young healthy subjects before and after citric acid stimulation. AB - BACKGROUND: Gender differences in the function and anatomical features of salivary glands are well known. However, specific gender differences in the biochemical composition and salivary flow rate (SFR) remain uncertain. Collection methods affect the assessment of the salivary composition and SFR, which are also highly affected by acid stimulation. METHODS: In the present study, we analyzed the differences in salivary characteristics of SFR, pH and salivary alpha-amylase (sAA) for 28 females and 27 males before and after citric acid stimulation, as measured by 3 different collection methods sequentially. RESULTS: Salivary pH values were significantly lower in females than that in males, both before and after stimulation, irrespective of collection methods. Salivary pH consistently increased after acid stimulation in both genders. Mean SFR in females before acid stimulation was significantly lower than that in males in all 3 samples collected. No gender difference in sAA was evident. CONCLUSION: Substantial gender differences in biochemistry and flow of saliva exist, and these findings are robust, as evidenced by reasonable consistency of the data among different saliva sampling methods. PMID- 27374300 TI - Falsely low plasma human chorionic gonadotropin (hCG) concentrations: Corrective actions implemented. PMID- 27374301 TI - Clinical usefulness of bone turnover marker concentrations in osteoporosis. AB - Current evidence continues to support the potential for bone turnover markers (BTM) to provide clinically useful information particularly for monitoring the efficacy of osteoporosis treatment. Many of the limitations identified earlier remain, principally in regard to the relationship between BTM and incident fractures. Important data are now available on reference interval values for CTX and PINP across a range of geographic regions and for individual clinical assays. An apparent lack of comparability between current clinical assays for CTX has become evident indicating the possible limitations of combining such data for meta-analyses. Harmonization of units for reporting serum/plasma CTX (ng/L) and PINP (MUg/L) is recommended. The development of international collaborations continues with an important initiative to combine BTM results from clinical trials in osteoporosis in a meta-analysis and an assay harmonization program are likely to be beneficial. It is possible that knowledge derived from clinical studies can further enhance fracture risk estimation tools with inclusion of BTM together with other independent risk factors. Further data of the relationships between the clinical assays for CTX and PINP as well as physiological and pre analytical factors contributing to variability in BTM concentrations are required. PMID- 27374302 TI - Whole-exome sequencing identifies compound heterozygous mutations in ARSA of two siblings presented with atypical onset of metachromatic leukodystrophy from a Chinese pedigree. AB - BACKGROUND: Metachromatic leukodystrophy (MLD) is a rare inherited lysosomal storage disorder caused mainly by variants in arylsulfatase A (ARSA) gene. MLD can be divided into three major clinical forms according to the age of onset: late infantile, juvenile, and adult. We report two siblings of late infantile MLD presenting with cerebellar ataxia as the only first clinical symptom. METHODS: Because of the unspecific neurological manifestation, whole-exome sequencing (WES) was performed to find disease-causing mutations for molecular diagnosis. Then successive MRI and ARSA activity determination were performed to further confirm the diagnosis. Moreover, the prenatal diagnosis was carried out on the basis of molecular diagnosis. RESULTS: The siblings exhibited compound heterozygous variants {[c.302G>T]+[c.1344dupC]} in the ARSA gene, and both of the variants have been reported as disease-causing mutations previously. The results of MRI and low ARSA activity confirmed the diagnosis of MLD. Prenatal diagnosis showed that the fetus was a heterozygous carrier. CONCLUSIONS: It is recommended that WES be considered as a first line diagnostic procedure to discover potential disease-causing genetic variants in affected individuals with hereditary traits but without definite clinical diagnosis. However, the final diagnosis should be confirmed by comprehensive evaluations including biochemical, enzymatic or imaging investigations. PMID- 27374303 TI - DNA injury is acutely enhanced in response to increasing bulks of aerobic physical exercise. AB - The aim of this study was to evaluate DNA damage in response to increasing bulks of aerobic physical exercise. Fifteen adult and trained athletes performed four sequential trials with increasing running distance (5-, 10-, 21- and 42-km) in different periods of the year. The gamma-H2AX foci parameters were analyzed before and 3h after the end of each trial. The values of all gamma-H2AX foci parameters were enhanced after the end of each trial, with values gradually increasing from the 5- to the 42-km trial. Interestingly, a minor increase of gamma-H2AX foci was still evident after 5- to 10-km running, but a much higher increase occurred when the running distance exceeded 21km. The generation of DNA injury was then magnified by running up to 42-km. The increase of each gamma-H2AX foci parameter was then found to be associated with both running distance and average intensity. In multivariate linear regression analysis, the running distance was significantly associated with average intensity and post-run variation in the percentage of cells with gamma-H2AX foci. We can hence conclude that aerobic exercise may generate an acute DNA damage in trained athletes, which is highly dependent upon running distance and average intensity. PMID- 27374304 TI - Biomarker development targeting unmet clinical needs. AB - BACKGROUND: The introduction of new biomarkers can lead to inappropriate utilization of tests if they do not fill in existing gaps in clinical care. We aimed to define a strategy and checklist for identifying unmet needs for biomarkers. METHODS: A multidisciplinary working group used a 4-step process: 1/ scoping literature review; 2/ face-to-face meetings to discuss scope, strategy and checklist items; 3/ iterative process of feedback and consensus to develop the checklist; 4/ testing and refinement of checklist items using case scenarios. RESULTS: We used clinical pathway mapping to identify clinical management decisions linking biomarker testing to health outcomes and developed a 14-item checklist organized into 4 domains: 1/ identifying and 2/ verifying the unmet need; 3/ validating the intended use; and 4/ assessing the feasibility of the new biomarker to influence clinical practice and health outcome. We present an outcome-focused approach that can be used by multiple stakeholders for any medical test, irrespective of the purpose and role of testing. CONCLUSIONS: The checklist intends to achieve more efficient biomarker development and translation into practice. We propose the checklist is field tested by stakeholders, and advocate the role of the clinical laboratory professional to foster trans-sector collaboration in this regard. PMID- 27374305 TI - Reply to the Editor- Device enabled left atrial appendage ligation-A word of caution. PMID- 27374307 TI - Ablation of complex fractionated electrograms is useful for catheter ablation of persistent atrial fibrillation: Protagonist point of view. PMID- 27374306 TI - Novel calmodulin mutations associated with congenital long QT syndrome affect calcium current in human cardiomyocytes. AB - BACKGROUND: Calmodulin (CaM) mutations are associated with cardiac arrhythmia susceptibility including congenital long QT syndrome (LQTS). OBJECTIVE: The purpose of this study was to determine the clinical, genetic, and functional features of 2 novel CaM mutations in children with life-threatening ventricular arrhythmias. METHODS: The clinical and genetic features of 2 congenital arrhythmia cases associated with 2 novel CaM gene mutations were ascertained. Biochemical and functional investigations were conducted on the 2 mutations. RESULTS: A novel de novo CALM2 mutation (D132H) was discovered by candidate gene screening in a male infant with prenatal bradycardia born to healthy parents. Postnatal course was complicated by profound bradycardia, prolonged corrected QT interval (651 ms), 2:1 atrioventricular block, and cardiogenic shock. He was resuscitated and was treated with a cardiac device. A second novel de novo mutation in CALM1 (D132V) was discovered by clinical exome sequencing in a 3-year old boy who suffered a witnessed cardiac arrest secondary to ventricular fibrillation. Electrocardiographic recording after successful resuscitation revealed a prolonged corrected QT interval of 574 ms. The Ca(2+) affinity of CaM D132H and CaM-D132V revealed extremely weak binding to the C-terminal domain, with significant structural perturbations noted for D132H. Voltage-clamp recordings of human induced pluripotent stem cell-derived cardiomyocytes transiently expressing wild-type or mutant CaM demonstrated that both mutations caused impaired Ca(2+)-dependent inactivation of voltage-gated Ca(2+) current. Neither mutant affected voltage-dependent inactivation. CONCLUSION: Our findings implicate impaired Ca(2+)-dependent inactivation in human cardiomyocytes as the plausible mechanism for long QT syndrome associated with 2 novel CaM mutations. The data further expand the spectrum of genotype and phenotype associated with calmodulinopathy. PMID- 27374308 TI - Ablation of complex fractionated electrograms may not be useful for catheter ablation of persistent atrial fibrillation. PMID- 27374309 TI - Perindopril for the prevention of atrial fibrillation recurrence after radiofrequency catheter ablation: One-year experience. AB - BACKGROUND: Recurrence of atrial fibrillation (AF) after ablation is still high. Perindopril plays an essential role in AF induction and maintenance. OBJECTIVE: We aimed to prove that perindopril (8 mg) could prevent recurrence after pulmonary vein isolation. METHODS: Patients with paroxysmal AF who received radiofrequency ablation were randomized to a 3-month course of perindopril 8 mg once daily (perindopril group) or placebo (placebo group). Angiotensin-II (Ang II) therapy and standard transthoracic echocardiography were performed. All 256 patients with paroxysmal AF who received radiofrequency ablation were randomized. And we followed them for complete 1 year. The 3-month recurrence and the 1-year recurrence were compared between the 2 groups. RESULTS: The 3-month recurrence of AF was observed in 33 (26.19%) of 126 patients in the placebo group vs 19 (14.62%) of 130 patients who received perindopril 8 mg once daily (chi2, P = .021). One-year recurrence of AF was observed in 36 (28.5%) of 126 patients in the placebo group as compared with 21 (16.2%) of 130 patients who received perindopril after 1 year (P = .017). The kappa value was 0.94 in the control group (P < .001) and 0.96 in the perindopril group (P < .001) between 3-month and 1-year recurrence. The Ang-II level was related to the left atrial distance with the reduction in AF recurrence (r = 0.17, P = .005 at 3 months; r = 0.25, P < .001 at 1 year). CONCLUSION: Perindopril is an effective and safe treatment for the prevention of AF recurrence after radiofrequency catheter ablation. This effect seems to be strongly associated with a significant decrease in Ang-II level and left atrial distance. PMID- 27374310 TI - Effect of epicardial cooling Peltier elements on atrial conduction: A proof-of concept study for a potentially painless method of atrial defibrillation. PMID- 27374311 TI - To the Editor- Device enabled left atrial appendage ligation-A word of caution. PMID- 27374312 TI - Oncogenic role of mortalin contributes to ovarian tumorigenesis by activating the MAPK-ERK pathway. AB - Mortalin is frequently overexpressed in human malignancies. Previous studies have suggested that mortalin contributes to ovarian cancer development and progression, but further investigation is warranted. The aim of this study is to elucidate the mechanism of mortalin in ovarian cancer development and progression. In this study, lentivirus-delivered mortalin short hairpin RNA (shRNA) was used to knockdown mortalin expression in A2780 and A2780/cis ovarian cancer cell lines, and lentiviral mortalin-pLVX-AcGFP was used to generate mortalin-overexpressing cell lines. The results demonstrated that decreased mortalin expression reduced ovarian cancer cell proliferation, colony formation, migration and invasion by Cell Counting Kit-8 assay, colony formation assay, wounding healing assay and Transwell cell invasion assay, respectively. Flow cytometry results suggested that mortalin promotes the G1 transition, leading to faster restoration of a normal cell-cycle distribution. Cell-cycle proteins, including C-myc and Cyclin-D1, significantly increased, and Cyclin-B1 remarkably decreased upon mortalin down-regulation. Western blot analysis showed that mortalin knockdown significantly decreased p-c-Raf and phospho-extracellular regulated protein kinases (p-ERK1/2) pathways but not the Jun N-terminal kinase pathway, whereas mortalin overexpression had the opposite effect. Taken together, these results indicate that mortalin is an oncogenic factor, and mitogen activated protein kinase-ERK signalling pathway activation by mortalin may contribute to ovarian cancer development and progression. PMID- 27374314 TI - VPS35: Two Ways to Recycle the Parathyroid Hormone Receptor (PTH1R) in Osteoblasts. PMID- 27374315 TI - Unraveling the molecular details of the innate immune response. PMID- 27374313 TI - Activation of PPARgamma by a Natural Flavonoid Modulator, Apigenin Ameliorates Obesity-Related Inflammation Via Regulation of Macrophage Polarization. AB - PPARgamma has emerged as a master regulator of macrophage polarization and is the molecular target of the thiazolidinedione drugs. Here we show that apigenin binds and activates PPARgamma by acting as a modulator. Activation of PPARgamma by apigenin blocks p65 translocation into nuclei through inhibition of p65/PPARgamma complex translocation into nuclei, thereby decreasing NF-kappaB activation and favoringM2 macrophage polarization. In HFD and ob/ob mice, apigenin significantly reverses M1 macrophage into M2 and reduces the infiltration of inflammatory cells in liver and adipose tissues, as well as decreases the levels of pro-inflammatory cytokines, thereby alleviating inflammation. Strikingly, apigenin reduces liver and muscular steatosis, decreases the levels of ALT, AST, TC and TG, improving glucose resistance obviously. Unlike rosiglitazone, apigenin does not cause significant weight gain, osteoporosis et al. Our findings identify apigenin as a modulator of PPARgamma and a potential lead compound for treatment of metabolic disorders. PMID- 27374316 TI - Spike-timing dependent inhibitory plasticity to learn a selective gating of backpropagating action potentials. AB - Inhibition is known to influence the forward-directed flow of information within neurons. However, also regulation of backward-directed signals, such as backpropagating action potentials (bAPs), can enrich the functional repertoire of local circuits. Inhibitory control of bAP spread, for example, can provide a switch for the plasticity of excitatory synapses. Although such a mechanism is possible, it requires a precise timing of inhibition to annihilate bAPs without impairment of forward-directed excitatory information flow. Here, we propose a specific learning rule for inhibitory synapses to automatically generate the correct timing to gate bAPs in pyramidal cells when embedded in a local circuit of feedforward inhibition. Based on computational modeling of multi-compartmental neurons with physiological properties, we demonstrate that a learning rule with anti-Hebbian shape can establish the required temporal precision. In contrast to classical spike-timing dependent plasticity of excitatory synapses, the proposed inhibitory learning mechanism does not necessarily require the definition of an upper bound of synaptic weights because of its tendency to self-terminate once annihilation of bAPs has been reached. Our study provides a functional context in which one of the many time-dependent learning rules that have been observed experimentally - specifically, a learning rule with anti-Hebbian shape - is assigned a relevant role for inhibitory synapses. Moreover, the described mechanism is compatible with an upregulation of excitatory plasticity by disinhibition. PMID- 27374317 TI - Highly Efficient Triplet Photosensitizers: A Systematic Approach to the Application of Ir(III) Complexes containing Extended Phenanthrolines. AB - A series of Ir(III) complexes, based on 1,10-phenanthroline featuring aryl acetylene chromophores, were prepared and investigated as triplet photosensitizers. The complexes were synthesized by Sonogashira cross-coupling reactions using a "chemistry-on-the-complex" method. The absorption properties and luminescence lifetimes were successfully tuned by controlling the number and type of light-harvesting group. Intense UV/Vis absorption was observed for the Ir(III) complexes with two light-harvesting groups at the 3- and 8-positions of the phenanthroline. The asymmetric Ir(III) complex (with a triphenylamine (TPA) and a pyrene moiety attached) exhibited the longest lifetime. Red emission was observed for all the complexes in deaerated solutions at room temperature. Their emission at low temperature (77 K) and nanosecond time-resolved transient difference absorption spectra revealed the origin of their triplet excited states. The singlet-oxygen ((1) O2 ) sensitization and triplet-triplet annihilation (TTA)-based upconversion were explored. Highly efficient TTA upconversion (PhiUC =28.1 %) and (1) O2 sensitization (PhiDelta =97.0 %) were achieved for the asymmetric Ir(III) complex, which showed intense absorption in the visible region (lambdaabs =482 nm, epsilon=50900 m(-1) cm(-1) ) and had a long-lived triplet excited state (53.3 MUs at RT). PMID- 27374318 TI - Synthesis, structure and physical properties of a low dimensional compound. AB - The crystal structure of (MU3-oxo)hexakis(cyanoacetato-kappaO,O')(cyanoacetato kappaO)diaquatriiron(III) cyanoacetic acid shows the formation of trinuclear complexes in a hydrogen-bond network that bonds all the molecules in a 3D arrangement. For this complex, within whose clusters the whole magnetic interaction takes place, 57Fe Mossbauer spectroscopy shows that the Fe cations are in the S=5/2 state in the temperature range 2-295K. The asymmetric broadening of the absorption peaks below 80K is consistent with strong antiferromagnetic interactions between the metal spins. The magnetization measurements also show the antiferromagnetic character of the spin ensemble and an ST=1/2 magnetic ground state typical of triangular systems with similar J between Fe-Fe pairs. PMID- 27374319 TI - The role of working memory in rapid instructed task learning and intention-based reflexivity: An individual differences examination. AB - The ability to efficiently follow novel task instructions (Rapid Instructed Task Learning, RITL) appears late in evolution, is required for successful collaborative teamwork, and appears to involve maintaining instructions in working-memory (WM). RITL is indexed by the efficiency in which the instructions are performed (RITL success) and by whether the instructions operate automatically (intention-based reflexivity). Based on prior normative work employing WM-load manipulations, we predicted that individual differences in WM would positively correlate with these RITL indices. Participants (N=175) performed the NEXT paradigm, which is used to assess RITL, and tests of choice reaction time, intelligence, and WM. Confirmatory factor analyses showed that, contrary to our predictions, successful performance in WM tasks did not predict RITL performance. Tests tapping general-fluid intelligence and reaction time positively correlated with RITL success. However, contrary to our predictions, RITL success positively correlated with little intention-based reflexivity. We suggest that for a RITL paradigm to produce intention-based reflexivity, its WM demand must be low, and, thus, performance does not reflect individual differences in WM. PMID- 27374321 TI - Biomimetic mineralization of recombinant collagen type I derived protein to obtain hybrid matrices for bone regeneration. AB - Understanding the mineralization mechanism of synthetic protein has recently aroused great interest especially in the development of advanced materials for bone regeneration. Herein, we propose the synthesis of composite materials through the mineralization of a recombinant collagen type I derived protein (RCP) enriched with RGD sequences in the presence of magnesium ions (Mg) to closer mimic bone composition. The role of both RCP and Mg ions in controlling the precipitation of the mineral phase is in depth evaluated. TEM and X-ray powder diffraction reveal the crystallization of nanocrystalline apatite (Ap) in all the evaluated conditions. However, Raman spectra point out also the precipitation of amorphous calcium phosphate (ACP). This amorphous phase is more evident when RCP and Mg are at work, indicating the synergistic role of both in stabilizing the amorphous precursor. In addition, hybrid matrices are prepared to tentatively address their effectiveness as scaffolds for bone tissue engineering. SEM and AFM imaging show an homogeneous mineral distribution on the RCP matrix mineralized in presence of Mg, which provides a surface roughness similar to that found in bone. Preliminary in vitro tests with pre-osteoblast cell line show good cell-material interaction on the matrices prepared in the presence of Mg. To the best of our knowledge this work represents the first attempt to mineralize recombinant collagen type I derived protein proving the simultaneous effect of the organic phase (RCP) and Mg on ACP stabilization. This study opens the possibility to engineer, through biomineralization process, advanced hybrid matrices for bone regeneration. PMID- 27374320 TI - Cellular electron cryo tomography and in situ sub-volume averaging reveal the context of microtubule-based processes. AB - Electron cryo-tomography (cryoET) is currently the only technique that allows the direct observation of proteins in their native cellular environment. Sub-volume averaging of electron tomograms offers a route to increase the signal-to-noise of repetitive biological structures, such improving the information content and interpretability of tomograms. We discuss the potential for sub-volume averaging in highlighting and investigating specific processes in situ, focusing on microtubule structure and viral infection. We show that (i) in situ sub-volume averaging from single tomograms can guide and complement segmentation of biological features, (ii) the in situ determination of the structure of individual viruses is possible as they infect a cell, and (iii) novel, transient processes can be imaged with high levels of detail. PMID- 27374322 TI - Does cannabidiol have a role in the treatment of schizophrenia? AB - Schizophrenia is a debilitating psychiatric disorder which places a significant emotional and economic strain on the individual and society-at-large. Unfortunately, currently available therapeutic strategies do not provide adequate relief and some patients are treatment-resistant. In this regard, cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, has shown significant promise as a potential antipsychotic for the treatment of schizophrenia. However, there is still considerable uncertainty about the mechanism of action of CBD as well as the brain regions which are thought to mediate its putative antipsychotic effects. We argue that further research on CBD is required to fast-track its progress to the clinic and in doing so, we may generate novel insights into the neurobiology of schizophrenia. PMID- 27374323 TI - Hallucinations in adolescents and risk for mental disorders and suicidal behaviour in adulthood: Prospective evidence from the MUSP birth cohort study. AB - BACKGROUND: Hallucinations, once equated with serious mental disorders, are common in adolescents. Given the high prevalence of hallucinations, it is important to determine if they are associated with adverse mental health outcomes in adulthood. This study compared the mental health outcomes of participants (aged 30-33years) in the Mater-University of Queensland Study of Pregnancy (MUSP) who reported hallucinations at (a) 14years only and (b) 14 and 21years versus cohort members without hallucinations. METHOD: Participants (n=333) were aged between 30 and 33years and (a) reported hallucinations on the Youth Self-Report Questionnaire at 14 and/or the Young Adult Self-Report Questionnaire at 21years and (b) controls (n=321) who did not report hallucinations. Lifetime diagnoses of mental disorders were ascertained by the Structured Clinical Interview for DSM Disorders (DSM IV-TR) administered by clinical psychologists. Suicidal behaviour was measured by self report. RESULTS: Hallucinations at 14years only were not associated with an increased risk of mental disorders in adulthood. Hallucinations reported at both 14 and 21years were associated with lifetime diagnoses of psychotic disorders (OR, 8.84; 95% CI: 1.61-48.43 and substance use disorders (OR, 2.34; 95% CI: 1.36-4.07) and also strongly associated with lifetime suicide attempts (OR, 7.11; 95% CI: 2.68-18.83). CONCLUSIONS: Most adolescents who experience hallucinations do not have an increased rate of mental disorder in adulthood; however, those with hallucinations that are experienced at more than one point in time are at increased risk of suicidal behaviour and both psychotic and non-psychotic psychopathology. PMID- 27374324 TI - Inhibition of skin inflammation by baicalin ultradeformable vesicles. AB - The topical efficacy of baicalin, a natural flavonoid isolated from Scutellaria baicalensis Georgi, which has several beneficial properties, such as antioxidative, antiviral, anti-inflammatory and antiproliferative, is hindered by its poor aqueous solubility and low skin permeability. Therefore, its incorporation into appropriate phospholipid vesicles could be a useful tool to improve its local activity. To this purpose, baicalin at increasing concentrations up to saturation, was incorporated in ultradeformable vesicles, which were small in size (~67nm), monodispersed (PI<0.19) and biocompatible, regardless of the concentration of baicalin, as confirmed by in vitro studies using fibroblasts. On the other hand, transdermal flux through human epidermis was concentration dependent. The in vivo results showed the significant anti inflammatory activity of baicalin loaded nanovesicles irrespective of the concentration used, as they were able to reduce the skin damage induced by the phorbol ester (TPA) application, even in comparison with dexamethasone, a synthetic drug with anti-inflammatory properties. Overall results indicate that ultradeformable vesicles are promising nanosystems for the improvement of cutaneous delivery of baicalin in the treatment of skin inflammation. PMID- 27374325 TI - Anaplastic and meningothelial meningiomas in a single tumor: A "dedifferentiated meningioma"? AB - The patient was a 74-year-old man, who developed progressive cognitive impairment and gait instability. Neuroradiological examination demonstrated a large and predominantly extra-axial tumor spreading over the bilateral frontal base, indicative of olfactory groove meningioma. The greater part of the resected tumor consisted of a dense, patternless proliferation of large, round or polygonal cells, and compactly fascicular growth of spindle cells. Tumor cells showed markedly anaplastic cytological features. In small areas of the tumor, a typical meningothelial meningioma showing no cellular atypism was found. Both tumor components were closely juxtaposed and no pathological features of an intermediate grade (atypical meningioma) were noted. Shortly after the operation, the patient developed a local recurrence of the tumor and multiple metastases to the cerebrum, bone and skin. Anaplastic meningioma is a rare, highly malignant neoplasm which arises de novo or as a result of the progressive transformation of a low-grade meningioma. The coexistence of anaplastic and low-grade components in a single meningeal tumor has been rarely reported. This dimorphic appearance is reminiscent of "dedifferentiation", a phenomenon infrequently seen in various mesenchymal and salivary gland neoplasms. We think that the term "dedifferentiated meningioma" can be appropriately applied to tumors such as that reported herein. PMID- 27374326 TI - A novel functional full-fat hard cheese containing liposomal nanoencapsulated green tea catechins: manufacture and recovery following simulated digestion. AB - (+)-Catechin or green tea extract were encapsulated in soy lecithin nanoliposomes and incorporated into a full-fat cheese, then ripened at 8 degrees C for 90 days. Cheese samples were subjected to simulated gastrointestinal digestion to measure total phenolic content (TPC) and antioxidant activity of the cheese digesta, and to determine the catechin recovery after digestion by high performance liquid chromatography (HPLC). Addition of catechin or green tea extract significantly (P <= 0.05) increased TPC and antioxidant activity (measured by ferric reducing antioxidant power and oxygen radical absorbance capacity) of the full-fat cheese without affecting pH or proximate composition. HPLC analysis confirmed retention of encapsulated catechins in the cheese curd; however, individual catechins were recovered in differing amounts (15-52%) from cheese digesta after 6 h of digestion. Transmission electron microscopy and Fourier transform infrared spectroscopy provided evidence for association of nanoliposomes with the surface of milk fat globules inside the cheese matrix. The study shows the potential for using cheese as a delivery vehicle for green tea antioxidants. PMID- 27374327 TI - Tropomodulin-3 is essential in asymmetric division during mouse oocyte maturation. AB - The dynamic polymerization and depolymerization of actin filaments is essential for various cellular processes such as cell migration, rotation, cytokinesis, and mammalian oocyte maturation. Tropomodulin 3 (Tmod3) binds to the slow-growing (pointed) ends of the actin filament, thereby protecting the filament from depolymerization. However, the roles of Tmod3 in mammalian oocyte maturation remain elusive. Tmod3 mRNA and protein is present at all stages of mouse oocyte maturation. Tmod3 protein is mainly localized in the cytoplasm and appears enriched near the chromosome during maturation. By knocking down or ectopically overexpressing Tmod3, we confirmed that Tmod3 regulate the level of the intracytoplasmic actin mesh and asymmetric spindle migration. Expression of N terminal Tmod3 (correspond to 1-155 amino acids), which contains the tropomyosin binding site, results in decreased density of the actin mesh, thereby demonstrating the importance of the interaction between tropomyosin and tropomodulin for the maintenance of the actin mesh. Taken together, these findings indicate that Tmod3 plays crucial roles in oocyte maturation, presumably by protecting the actin filament from depolymerization and thereby controlling the density of the cytoplasmic actin mesh. PMID- 27374328 TI - Adjacent Codons Act in Concert to Modulate Translation Efficiency in Yeast. AB - Translation elongation efficiency is largely thought of as the sum of decoding efficiencies for individual codons. Here, we find that adjacent codon pairs modulate translation efficiency. Deploying an approach in Saccharomyces cerevisiae that scored the expression of over 35,000 GFP variants in which three adjacent codons were randomized, we have identified 17 pairs of adjacent codons associated with reduced expression. For many pairs, codon order is obligatory for inhibition, implying a more complex interaction than a simple additive effect. Inhibition mediated by adjacent codons occurs during translation itself as GFP expression is restored by increased tRNA levels or by non-native tRNAs with exact matching anticodons. Inhibition operates in endogenous genes, based on analysis of ribosome profiling data. Our findings suggest translation efficiency is modulated by an interplay between tRNAs at adjacent sites in the ribosome and that this concerted effect needs to be considered in predicting the functional consequences of codon choice. PMID- 27374329 TI - Mitotic Checkpoint Regulators Control Insulin Signaling and Metabolic Homeostasis. AB - Insulin signaling regulates many facets of animal physiology. Its dysregulation causes diabetes and other metabolic disorders. The spindle checkpoint proteins MAD2 and BUBR1 prevent precocious chromosome segregation and suppress aneuploidy. The MAD2 inhibitory protein p31(comet) promotes checkpoint inactivation and timely chromosome segregation. Here, we show that whole-body p31(comet) knockout mice die soon after birth and have reduced hepatic glycogen. Liver-specific ablation of p31(comet) causes insulin resistance, hyperinsulinemia, glucose intolerance, and hyperglycemia and diminishes the plasma membrane localization of the insulin receptor (IR) in hepatocytes. MAD2 directly binds to IR and facilitates BUBR1-dependent recruitment of the clathrin adaptor AP2 to IR. p31(comet) blocks the MAD2-BUBR1 interaction and prevents spontaneous clathrin mediated IR endocytosis. BUBR1 deficiency enhances insulin sensitivity in mice. BUBR1 depletion in hepatocytes or the expression of MAD2-binding-deficient IR suppresses the metabolic phenotypes of p31(comet) ablation. Our findings establish a major IR regulatory mechanism and link guardians of chromosome stability to nutrient metabolism. PMID- 27374330 TI - The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of Mitochondria. AB - Brown and beige adipocytes are specialized cells that express uncoupling protein 1 (UCP1) and dissipate chemical energy as heat. These cells likely possess alternative UCP1-independent thermogenic mechanisms. Here, we identify a secreted enzyme, peptidase M20 domain containing 1 (PM20D1), that is enriched in UCP1(+) versus UCP1(-) adipocytes. We demonstrate that PM20D1 is a bidirectional enzyme in vitro, catalyzing both the condensation of fatty acids and amino acids to generate N-acyl amino acids and also the reverse hydrolytic reaction. N-acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. Mice with increased circulating PM20D1 have augmented respiration and increased N-acyl amino acids in blood. Lastly, administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure. These data identify an enzymatic node and a family of metabolites that regulate energy homeostasis. This pathway might be useful for treating obesity and associated disorders. PMID- 27374331 TI - Hexokinase Is an Innate Immune Receptor for the Detection of Bacterial Peptidoglycan. AB - Degradation of Gram-positive bacterial cell wall peptidoglycan in macrophage and dendritic cell phagosomes leads to activation of the NLRP3 inflammasome, a cytosolic complex that regulates processing and secretion of interleukin (IL) 1beta and IL-18. While many inflammatory responses to peptidoglycan are mediated by detection of its muramyl dipeptide component in the cytosol by NOD2, we report here that NLRP3 inflammasome activation is caused by release of N acetylglucosamine that is detected in the cytosol by the glycolytic enzyme hexokinase. Inhibition of hexokinase by N-acetylglucosamine causes its dissociation from mitochondria outer membranes, and we found that this is sufficient to activate the NLRP3 inflammasome. In addition, we observed that glycolytic inhibitors and metabolic conditions affecting hexokinase function and localization induce inflammasome activation. While previous studies have demonstrated that signaling by pattern recognition receptors can regulate metabolic processes, this study shows that a metabolic enzyme can act as a pattern recognition receptor. PAPERCLIP. PMID- 27374332 TI - Nfib Promotes Metastasis through a Widespread Increase in Chromatin Accessibility. AB - Metastases are the main cause of cancer deaths, but the mechanisms underlying metastatic progression remain poorly understood. We isolated pure populations of cancer cells from primary tumors and metastases from a genetically engineered mouse model of human small cell lung cancer (SCLC) to investigate the mechanisms that drive the metastatic spread of this lethal cancer. Genome-wide characterization of chromatin accessibility revealed the opening of large numbers of distal regulatory elements across the genome during metastatic progression. These changes correlate with copy number amplification of the Nfib locus, and differentially accessible sites were highly enriched for Nfib transcription factor binding sites. Nfib is necessary and sufficient to increase chromatin accessibility at a large subset of the intergenic regions. Nfib promotes pro metastatic neuronal gene expression programs and drives the metastatic ability of SCLC cells. The identification of widespread chromatin changes during SCLC progression reveals an unexpected global reprogramming during metastatic progression. PMID- 27374333 TI - Compositional Control of Phase-Separated Cellular Bodies. AB - Cellular bodies such as P bodies and PML nuclear bodies (PML NBs) appear to be phase-separated liquids organized by multivalent interactions among proteins and RNA molecules. Although many components of various cellular bodies are known, general principles that define body composition are lacking. We modeled cellular bodies using several engineered multivalent proteins and RNA. In vitro and in cells, these scaffold molecules form phase-separated liquids that concentrate low valency client proteins. Clients partition differently depending on the ratio of scaffolds, with a sharp switch across the phase diagram diagonal. Composition can switch rapidly through changes in scaffold concentration or valency. Natural PML NBs and P bodies show analogous partitioning behavior, suggesting how their compositions could be controlled by levels of PML SUMOylation or cellular mRNA concentration, respectively. The data suggest a conceptual framework for considering the composition and control thereof of cellular bodies assembled through heterotypic multivalent interactions. PMID- 27374334 TI - An Abundant Class of Non-coding DNA Can Prevent Stochastic Gene Silencing in the C. elegans Germline. AB - Cells benefit from silencing foreign genetic elements but must simultaneously avoid inactivating endogenous genes. Although chromatin modifications and RNAs contribute to maintenance of silenced states, the establishment of silenced regions will inevitably reflect underlying DNA sequence and/or structure. Here, we demonstrate that a pervasive non-coding DNA feature in Caenorhabditis elegans, characterized by 10-base pair periodic An/Tn-clusters (PATCs), can license transgenes for germline expression within repressive chromatin domains. Transgenes containing natural or synthetic PATCs are resistant to position effect variegation and stochastic silencing in the germline. Among endogenous genes, intron length and PATC-character undergo dramatic changes as orthologs move from active to repressive chromatin over evolutionary time, indicating a dynamic character to the An/Tn periodicity. We propose that PATCs form the basis of a cellular immune system, identifying certain endogenous genes in heterochromatic contexts as privileged while foreign DNA can be suppressed with no requirement for a cellular memory of prior exposure. PMID- 27374335 TI - Learning to Associate Orientation with Color in Early Visual Areas by Associative Decoded fMRI Neurofeedback. AB - Associative learning is an essential brain process where the contingency of different items increases after training. Associative learning has been found to occur in many brain regions [1-4]. However, there is no clear evidence that associative learning of visual features occurs in early visual areas, although a number of studies have indicated that learning of a single visual feature (perceptual learning) involves early visual areas [5-8]. Here, via decoded fMRI neurofeedback termed "DecNef" [9], we tested whether associative learning of orientation and color can be created in early visual areas. During 3 days of training, DecNef induced fMRI signal patterns that corresponded to a specific target color (red) mostly in early visual areas while a vertical achromatic grating was physically presented to participants. As a result, participants came to perceive "red" significantly more frequently than "green" in an achromatic vertical grating. This effect was also observed 3-5 months after the training. These results suggest that long-term associative learning of two different visual features such as orientation and color was created, most likely in early visual areas. This newly extended technique that induces associative learning is called "A-DecNef," and it may be used as an important tool for understanding and modifying brain functions because associations are fundamental and ubiquitous functions in the brain. PMID- 27374336 TI - Changing Balance of Spinal Cord Excitability and Nociceptive Brain Activity in Early Human Development. AB - In adults, nociceptive reflexes and behavioral responses are modulated by a network of brain regions via descending projections to the spinal dorsal horn [1]. Coordinated responses to noxious inputs manifest from a balance of descending facilitation and inhibition. In contrast, young infants display exaggerated and uncoordinated limb reflexes [2]. Our understanding of nociceptive processing in the infant brain has been advanced by the use of electrophysiological and hemodynamic imaging [3-6]. From approximately 35 weeks' gestation, nociceptive-specific patterns of brain activity emerge [7], whereas prior to this, non-specific bursts of activity occur in response to noxious, tactile, visual, and auditory stimulation [7-10]. During the preterm period, refinement of spinal cord excitability is also observed: reflex duration shortens, response threshold increases, and improved discrimination between tactile and noxious events occurs [2, 11, 12]. However, the development of descending modulation in human infants remains relatively unexplored. In 40 infants aged 28-42 weeks' gestation, we examined the relationship between nociceptive brain activity and spinal reflex withdrawal activity in response to a clinically essential noxious procedure. Nociceptive-specific brain activity increases in magnitude with gestational age, whereas reflex withdrawal activity decreases in magnitude, duration, and latency across the same developmental period. By recording brain and spinal cord activity in the same infants, we demonstrate that the maturation of nociceptive brain activity is concomitant with the refinement of noxious-evoked limb reflexes. We postulate that, consistent with studies in animals, infant reflexes are influenced by the development of top down inhibitory modulation from maturing subcortical and cortical brain networks. PMID- 27374338 TI - A Representation of Effort in Decision-Making and Motor Control. AB - Given two rewarding stimuli, animals tend to choose the more rewarding (or less effortful) option. However, they also move faster toward that stimulus [1-5]. This suggests that reward and effort not only affect decision-making, they also influence motor control [6, 7]. How does the brain compute the effort requirements of a task? Here, we considered data acquired during walking, reaching, flying, or isometric force production. In analyzing the decision-making and motor-control behaviors of various animals, we considered the possibility that the brain may estimate effort objectively, via the metabolic energy consumed to produce the action. We measured the energetic cost of reaching and found that, like walking, it was convex in time, with a global minimum, implying that there existed a movement speed that minimized effort. However, reward made it worthwhile to be energetically inefficient. Using a framework in which utility of an action depended on reward and energetic cost, both discounted in time, we found that it was possible to account for a body of data in which animals were free to choose how to move (reach slow or fast), as well as what to do (walk or fly, produce force F1 or F2). We suggest that some forms of decision-making and motor control may share a common utility in which the brain represents the effort associated with performing an action objectively via its metabolic energy cost and then, like reward, temporally discounts it as a function of movement duration. PMID- 27374337 TI - Electrical Stimulation of Visual Cortex Can Immediately Improve Spatial Vision. AB - We can improve human vision by correcting the optics of our lenses [1-3]. However, after the eye transduces the light, visual cortex has its own limitations that are challenging to correct [4]. Overcoming these limitations has typically involved innovative training regimes that improve vision across many days [5, 6]. In the present study, we wanted to determine whether it is possible to immediately improve the precision of spatial vision with noninvasive direct current stimulation. Previous work suggested that visual processing could be modulated with such stimulation [7-9]. However, the short duration and variability of such effects made it seem unlikely that spatial vision could be improved for more than several minutes [7, 10]. Here we show that visual acuity in the parafoveal belt can be immediately improved by delivering noninvasive direct current to visual cortex. Twenty minutes of anodal stimulation improved subjects' vernier acuity by approximately 15% and increased the amplitude of the earliest visually evoked potentials in lockstep with the behavioral effects. When we reversed the orientation of the electric field, we impaired resolution and reduced the amplitude of visually evoked potentials. Next, we found that anodal stimulation improved acuity enough to be measurable with the relatively coarse Snellen test and that subjects with the poorest acuity benefited the most from stimulation. Finally, we found that stimulation-induced acuity improvements were accompanied by changes in contrast sensitivity at high spatial frequencies. PMID- 27374339 TI - The structure of sperm Izumo1 reveals unexpected similarities with Plasmodium invasion proteins. AB - Fertilization, the culminating event in sexual reproduction, occurs when haploid sperm and egg recognize each other and fuse to form a diploid zygote. In mammals this process critically depends on the interaction between Izumo1, a protein exposed on the equatorial segment of acrosome-reacted sperm, and the egg plasma membrane-anchored receptor Juno [1,2]. The molecular mechanism triggering gamete fusion is unresolved because both Izumo1 and Juno lack sequence similarity to known membrane fusogens. Here we report the crystal structure of Izumo1, which reveals a membrane distal region composed of a four-helix bundle connected to a carboxy-terminal immunoglobulin (Ig)-like domain through a beta-hairpin stabilized by disulfide bonds. Remarkably, different regions of Izumo1 display significant structural similarities to two proteins expressed by the invasive sporozoite stage of Plasmodium parasites: SPECT1, which is essential for host cell traversal and hepatocyte invasion [3]; and TRAP, which is necessary for gliding motility and invasion [4]. These observations suggest a link between the molecular mechanisms underlying host cell invasion by the malaria parasite and gamete membrane fusion at fertilization. PMID- 27374340 TI - Visualizing and Quantifying Intracellular Behavior and Abundance of the Core Circadian Clock Protein PERIOD2. AB - Transcriptional-translational feedback loops (TTFLs) are a conserved molecular motif of circadian clocks. The principal clock in mammals is the suprachiasmatic nucleus (SCN) of the hypothalamus. In SCN neurons, auto-regulatory feedback on core clock genes Period (Per) and Cryptochrome (Cry) following nuclear entry of their protein products is the basis of circadian oscillation [1, 2]. In Drosophila clock neurons, the movement of dPer into the nucleus is subject to a circadian gate that generates a delay in the TTFL, and this delay is thought to be critical for oscillation [3, 4]. Analysis of the Drosophila clock has strongly influenced models of the mammalian clock, and such models typically infer complex spatiotemporal, intracellular behaviors of mammalian clock proteins. There are, however, no direct measures of the intracellular behavior of endogenous circadian proteins to support this: dynamic analyses have been limited and often have no circadian dimension [5-7]. We therefore generated a knockin mouse expressing a fluorescent fusion of native PER2 protein (PER2::VENUS) for live imaging. PER2::VENUS recapitulates the circadian functions of wild-type PER2 and, importantly, the behavior of PER2::VENUS runs counter to the Drosophila model: it does not exhibit circadian gating of nuclear entry. Using fluorescent imaging of PER2::VENUS, we acquired the first measures of mobility, molecular concentration, and localization of an endogenous circadian protein in individual mammalian cells, and we showed how the mobility and nuclear translocation of PER2 are regulated by casein kinase. These results provide new qualitative and quantitative insights into the cellular mechanism of the mammalian circadian clock. PMID- 27374341 TI - The Genome of Intoshia linei Affirms Orthonectids as Highly Simplified Spiralians. AB - Orthonectids are rare parasites of marine invertebrates [1] that are commonly treated in textbooks as a taxon of uncertain affinity [2]. Trophic forms of orthonectids reside in the tissues of their hosts as multinucleated plasmodia, generating short-lived, worm-like ciliated female and male organisms that exit into the environment for copulation [3]. These ephemeral males and females are composed of just several hundred somatic cells and are deprived of digestive, circulatory, or excretory systems. Since their discovery in the 19(th) century, the orthonectids were described as organisms with no differentiated cell types and considered as part of Mesozoa, a putative link between multicellular animals and their unicellular relatives. More recently, this view was challenged as the new data suggested that orthonectids are animals that became simplified due to their parasitic way of life [3, 4]. Here, we report the genomic sequence of Intoshia linei, one of about 20 known species of orthonectids. The genomic data confirm recent morphological analysis asserting that orthonectids are members of Spiralia and possess muscular and nervous systems [5]. The 43-Mbp genome of I. linei encodes about 9,000 genes and retains those essential for the development and activity of muscular and nervous systems. The simplification of orthonectid body plan is associated with considerable reduction of metazoan developmental genes, leaving what might be viewed as the minimal gene set necessary to retain critical bilaterian features. PMID- 27374342 TI - Pea Plants Show Risk Sensitivity. AB - Sensitivity to variability in resources has been documented in humans, primates, birds, and social insects, but the fit between empirical results and the predictions of risk sensitivity theory (RST), which aims to explain this sensitivity in adaptive terms, is weak [1]. RST predicts that agents should switch between risk proneness and risk aversion depending on state and circumstances, especially according to the richness of the least variable option [2]. Unrealistic assumptions about agents' information processing mechanisms and poor knowledge of the extent to which variability imposes specific selection in nature are strong candidates to explain the gap between theory and data. RST's rationale also applies to plants, where it has not hitherto been tested. Given the differences between animals' and plants' information processing mechanisms, such tests should help unravel the conflicts between theory and data. Measuring root growth allocation by split-root pea plants, we show that they favor variability when mean nutrient levels are low and the opposite when they are high, supporting the most widespread RST prediction. However, the combination of non-linear effects of nitrogen availability at local and systemic levels may explain some of these effects as a consequence of mechanisms not necessarily evolved to cope with variance [3, 4]. This resembles animal examples in which properties of perception and learning cause risk sensitivity even though they are not risk adaptations [5]. PMID- 27374343 TI - Neural Mechanisms Generating Orientation Selectivity in the Retina. AB - The orientation of visual stimuli is a salient feature of visual scenes. In vertebrates, the first neural processing steps generating orientation selectivity take place in the retina. Here, we dissect an orientation-selective circuit in the larval zebrafish retina and describe its underlying synaptic, cellular, and molecular mechanisms. We genetically identify a class of amacrine cells (ACs) with elongated dendritic arbors that show orientation tuning. Both selective optogenetic ablation of ACs marked by the cell-adhesion molecule Teneurin-3 (Tenm3) and pharmacological interference with their function demonstrate that these cells are critical components for orientation selectivity in retinal ganglion cells (RGCs) by being a source of tuned GABAergic inhibition. Moreover, our morphological analyses reveal that Tenm3(+) ACs and orientation-selective RGCs co-stratify their dendrites in the inner plexiform layer, and that Tenm3(+) ACs require Tenm3 to acquire their correct dendritic stratification. Finally, we show that orientation tuning is present also among bipolar cell presynaptic terminals. Our results define a neural circuit underlying orientation selectivity in the vertebrate retina and characterize cellular and molecular requirements for its assembly. PMID- 27374345 TI - Weight Control Behavior as an Indicator of Adolescent Psychological Well-Being. AB - BACKGROUND: Adolescence is a critical time for the development of psychological well-being. Weight gain and the emergence of body image concerns during this period can lead to the development of negative psychological states. To explore this issue, we examined the relationship between weight control behavior (WCB; ie, trying to lose, gain, stay the same, or do nothing about weight) and levels of depression and self-esteem. METHODS: Adolescents (508 boys, 502 girls; Mage = 12.32 +/- .88 years) completed a survey that assessed WCB, depression, and self esteem. Descriptive discriminant analysis was used to analyze WCB group differences on psychological well-being. Multivariate post hoc analysis further examined group differences. Structure coefficients indicated the relative importance of each dependent variable in boys and girls. RESULTS: Results indicated that, among both sexes, WCB was significantly related to depression and self-esteem. Individuals trying to lose weight had lower levels of psychological well-being than the other groups. CONCLUSIONS: Adolescents trying to lose weight reported the lowest psychological well-being scores whereas those not doing anything to control weight reported the highest levels of psychological well being. These findings have important implications for screening and education programs designed to monitor and support adolescent psychological well-being. PMID- 27374346 TI - School Breakfast-Club Program Changes and Youth Eating Breakfast During the School Week in the COMPASS Study. AB - BACKGROUND: Despite the importance of breakfast consumption, breakfast skipping is common among Canadian youth. This study examines how changes to school-based breakfast programs are associated with breakfast-skipping behavior. METHODS: Using school-level longitudinal data from Year 1 (Y1 : 2012-2013) and Year 2 (Y2 : 2013-2014) of the COMPASS study, quasi-experimental methods evaluated the impact over time that changes to school-based breakfast programs had on breakfast skipping or participating in school-based breakfast program. RESULTS: Between Y1 and Y2 , the school-level prevalence of breakfast skipping (54.5%-54.9%) and breakfast program participation (12.3%-13.6%) increased. Of the 43 participating schools, 5 implemented a new school breakfast program. Among the intervention schools, 1 school (School 4) observed a significant, and 1 school (School 3) observed a significant increase in the school-level prevalence of skipping breakfast; there was no significant change in the other 3 intervention schools. CONCLUSIONS: Despite the availability of free school breakfast programs, the majority of youth skipped breakfast at least once a school week. Owing to the variation in the types of programs implemented, additional evaluation evidence is necessary to determine which students benefited the most from these programs. PMID- 27374344 TI - Functional Characterization of ATP-Binding Cassette Transporter A3 Mutations from Infants with Respiratory Distress Syndrome. AB - Mutations in the ATP-binding cassette transporter A3 gene (ABCA3) result in severe neonatal respiratory distress syndrome and childhood interstitial lung disease. As most ABCA3 mutations are rare or private, determination of mutation pathogenicity is often based on results from in silico prediction tools, identification in unrelated diseased individuals, statistical association studies, or expert opinion. Functional biologic studies of ABCA3 mutations are needed to confirm mutation pathogenicity and inform clinical decision making. Our objective was to functionally characterize two ABCA3 mutations (p.R288K and p.R1474W) identified among term and late-preterm infants with respiratory distress syndrome with unclear pathogenicity in a genetically versatile model system. We performed transient transfection of HEK293T cells with wild-type or mutant ABCA3 alleles to assess protein processing with immunoblotting. We used transduction of A549 cells with adenoviral vectors, which concurrently silenced endogenous ABCA3 and expressed either wild-type or mutant ABCA3 alleles (p.R288K and p.R1474W) to assess immunofluorescent localization, ATPase activity, and organelle ultrastructure. Both ABCA3 mutations (p.R288K and p.R1474W) encoded proteins with reduced ATPase activity but with normal intracellular localization and protein processing. Ultrastructural phenotypes of lamellar body-like vesicles in A549 cells transduced with mutant alleles were similar to wild type. Mutant proteins encoded by ABCA3 mutations p.R288K and p.R1474W had reduced ATPase activity, a biologically plausible explanation for disruption of surfactant metabolism by impaired phospholipid transport into the lamellar body. These results also demonstrate the usefulness of a genetically versatile, human model system for functional characterization of ABCA3 mutations with unclear pathogenicity. PMID- 27374347 TI - Planning Adolescent Mental Health Promotion Programming in Saskatoon. AB - BACKGROUND: We assessed associations between key demographic risk factors and the outcome of depressed mood in Saskatoon, Saskatchewan, to inform the planning and implementation of mental health promotion programming in schools. METHODS: In the 2008/2009 school year, 3958 students from grades 5 through 8 from 76 elementary schools completed questions regarding depressed mood on the Student Health Survey administered by the Saskatoon Health Region. The demographic risk factors for depressed mood considered in this study included age, sex, cultural status, and neighborhood income, as well as the role of school and age cohorts or grades within schools. RESULTS: We found Aboriginal students were significantly more likely to report moderate/severe depressed mood than other students. We also found older female adolescents were significantly more likely to report moderate/severe depressed mood. Neighborhood income explained the largest proportion (40%) of depressed mood differences between schools. CONCLUSIONS: These results can inform the planning and implementation of mental health promotion programming by the health sector in Saskatoon's elementary schools, including an appropriate balance between targeted and population-based interventions that address both the distal and proximal determinants of depressed mood in adolescents. PMID- 27374348 TI - After-School Program Implementation in Urban Environments: Increasing Engagement Among Adolescent Youth. AB - BACKGROUND: After-school programs (ASPs) play a crucial role in supplementing the present school day. However, implementing ASPs in the urban environment and among adolescents (grades 6-12) poses unique challenges. The purpose of this study was to conduct a systematic literature review to identify evidence-based barriers and facilitators to after-school programming in urban school environments. METHODS: Twenty-five publications meeting the authors' inclusion criteria over the past 10 years were reviewed and synthesized. RESULTS: Results demonstrated that the demand for ASPs is increasing. Several barriers, including staffing, funding, resources, transportation, and space, were identified. Specific challenges regarding the implementation of ASPs for adolescents in urban areas were also determined. A number of best practices were identified along with benefits for academic engagement and social-emotional coping skill development. CONCLUSIONS: Efforts to address these specific barriers and facilitators to ASP implementation may contribute to improving broader health and academic outcomes among adolescent youth. PMID- 27374349 TI - Effectiveness of an Adaptation of the Project Connect Health Systems Intervention: Youth and Clinic-Level Findings. AB - BACKGROUND: The Project Connect Health Systems Intervention (Project Connect) uses a systematic process of collecting community and healthcare infrastructure information to craft a referral guide highlighting local healthcare providers who provide high quality sexual and reproductive healthcare. Previous self-report data on healthcare usage indicated Project Connect was successful with sexually experienced female youth, where it increased rates of human immunodeficiency virus (HIV) and sexually transmitted disease (STD) testing and receipt of contraception. This adaption of Project Connect examined its effectiveness in a new context and via collection of clinic encounter-level data. METHODS: Project Connect was implemented in 3 high schools. (only 2 schools remained open throughout the entire project period). Participant recruitment and data collection occurred in 5 of 8 participating health clinics. Students completed Youth Surveys (N = 608) and a Clinic Survey (paired with medical data abstraction in 2 clinics [N = 305]). RESULTS: Students were more likely than nonstudents to report having reached a clinic via Project Connect. Nearly 40% of students attended a Project Connect school, with 32.7% using Project Connect to reach the clinic. Students were most likely to have been referred by a school nurse or coach. CONCLUSIONS: Project Connect is a low-cost, sustainable structural intervention with multiple applications within schools, either as a standalone intervention or in combination with ongoing efforts. PMID- 27374350 TI - Evaluation of the LiveWell@School Food Initiative Shows Increases in Scratch Cooking and Improvement in Nutritional Content. AB - BACKGROUND: The purpose of this evaluation was to examine the effects of the LiveWell@School Food Initiative (LW@SFI), a Colorado-based childhood obesity prevention program that partners with school districts to enable them to serve more scratch cooked foods through culinary training, action planning, and equipment grants. METHODS: This evaluation used a quasi-experimental design that examined menu cycles prior to entering the LW@SFI and approximately 1 year later. A review of school menus with food service directors from 9 Colorado school districts was conducted. RESULTS: Data show that districts changed an average of 17.4 entrees and 19.7 side dishes over the course of the year. Changes to serving scratch cooked foods were highest for sauces (an increase of 40.5%). No districts were cooking beans/legumes from scratch during baseline or at follow-up. Across the 9 districts, 7 observed statistically significant pre-post reductions in sodium, 4 in fat, 5 in saturated fat, and 3 in calories. CONCLUSIONS: Within a year of implementing the LW@SFI, school districts increased the proportion of fresh, scratch cooked foods they offered and this was associated with some decreases in calories, fat, saturated fat, and sodium, contributing to healthier school food environments. PMID- 27374351 TI - Certified School Nurse Perspectives on State-Mandated Hearing Screens. AB - BACKGROUND: Approximately 15% of children in the United States 6-19 years of age have hearing loss. Even mild, unilateral hearing loss may adversely affect educational success. In 2014, the Pennsylvania Department of Health (PA DOH) began updating the 2001 regulations on state-mandated school hearing screens. To inform the updates, a needs assessment was conducted with PA-certified school nurses (CSNs) regarding current screening practice and potential barriers to making changes. METHODS: A 42-item electronic survey of CSNs developed with pediatricians, audiologists, nurses, and the PA DOH was administered in October 2014. RESULTS: There were 536 completed surveys. Most CSNs (50.8%) screened 251 500 students annually. Only 35.8% strictly followed PA DOH protocol, while 51.6% followed protocol and added nonguideline frequencies. Over half of screens (60.2%) were conducted in places where other people were present. Most CSNs (82.5%) reported annual audiometer calibration, but 92.4% were unsure whether the calibration was exhaustive or limited. Reported barriers to change included time, cost, and staffing. CONCLUSIONS: As most CSNs added frequencies to the PA DOH hearing screen, an update with added frequencies should be well accepted. Clarification regarding test environment and exhaustive audiometer calibration is needed. Adherence to best practice may be optimized by addressing CSN reported barriers to change. PMID- 27374352 TI - Associations of Teen Dating Violence Victimization With School Violence and Bullying Among US High School Students. AB - BACKGROUND: Teen dating violence (TDV) negatively impacts health, mental and physical well-being, and school performance. METHODS: Data from a nationally representative sample of high school students participating in the Centers for Disease Control and Prevention (CDC)'s 2013 Youth Risk Behavior Survey (YRBS) are used to demonstrate associations of physical and sexual TDV with school violence related experiences and behaviors, including bullying victimization. Bivariate and adjusted sex-stratified regressions assessed relationships between TDV and school violence-related experiences and behaviors. RESULTS: Compared to students not reporting TDV, those experiencing both physical and sexual TDV were more likely to report carrying a weapon at school, missing school because they felt unsafe, being threatened or injured with a weapon on school property, having a physical fight at school, and being bullied on school property. CONCLUSIONS: School-based prevention efforts should target multiple forms of violence. PMID- 27374353 TI - Selective detection and complete identification of triglycerides in cortical bone by high-resolution (1)H MAS NMR spectroscopy. AB - Using (1)H-based magic angle spinning solid-state NMR spectroscopy, we report an atomistic-level characterization of triglycerides in compact cortical bone. By suppressing contributions from immobile molecules present in bone, we show that a (1)H-based constant-time uniform-sign cross-peak (CTUC) two-dimensional COSY-type experiment that correlates the chemical shifts of protons can selectively detect a mobile triglyceride layer as the main component of small lipid droplets embedded on the surface of collagen fibrils. High sensitivity and resolution afforded by this NMR approach could be potentially utilized to investigate the origin of triglycerides and their pathological roles associated with bone fractures, diseases, and aging. PMID- 27374354 TI - Prospective observational study of midtarsal joint sprain: Epidemiological and ultrasonographic analysis. AB - INTRODUCTION: Foot and ankle injuries (FAI) are very common, with about 6000 cases per day in France. Unlike lateral ankle sprain (LAS), the diagnosis of midtarsal joint sprain (MJS, also known as Chopart's joint sprain) is not widely known. This prospective study aims to detail the epidemiology of MJS and compare it to LAS. PATIENTS AND METHOD: The study was conducted within our institution over a period of 16 months. Patients with clinical signs predictive of MJS without radiographic bone lesion underwent ultrasound assessment. MJS was diagnosed in case of at least 1 lesion of the dorsal midtarsal joint ligaments. RESULTS: A total of 2412 patients consulted for FAI; 188 had clinical and radiographic criteria for ultrasound examination. Eighty-two cases of MJS were diagnosed (3.4% of FAIs). Sports injuries were more frequent in MJS (P=0.04), and mechanisms more varied than in LAS, with inversion injury in 75% of cases and plantar hyperflexion in 22%. Sprain was severe in 70% of cases, with complete ligament tear. Clinical and ultrasound analyses correlated in only 40% of cases of MJS, versus 98% for LAS. CONCLUSION: MJS is frequent, difficult to diagnose clinically, and often severe. Clinical presentation and injury mechanisms differ from ankle sprain. Ultrasound seems to be an indispensable tool in diagnosis. PMID- 27374355 TI - Comments on the three papers by the FDA/CDER research team on the regulatory perspective of the missing data problem. AB - This communication comments on the three papers by the FDA CDER research team on the regulatory perspective of the missing data problem. The focus is on two topics: causal estimand and sensitivity analysis. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27374356 TI - Commentary for the Missing Data Working Group's perspective for regulatory clinical trials, estimands, and sensitivity analyses. PMID- 27374358 TI - "SIOCMF" and "Minerva Stomatologica". PMID- 27374359 TI - Prevalence and distribution of oral mucosal non-malignant lesions in the western Sicilian population. AB - BACKGROUNG: The aim of the present study was to determine the prevalence of oral mucosal non-malignant lesions in the Sicilian population. In addition, we evaluated the association between each oral lesion and its risk factors. METHODS: This study analyzed a total of 2539 consecutive patients, attending the Department of Surgical, Oncological and Stomatological Disciplines of Palermo University, who were examined for the presence of various oral lesions during the period from January 2012 and February 2015. RESULTS: The sample consisted of 1330 (52%) female and 1209 (48%) male. The age ranged from 13-86 years with a mean age of 47.16 years. Among these subjects 1495 (58%), presented one or more lesions. All subjects were Caucasian. The most common lesion diagnosed was coated/hairy tongue affecting 16.7% of the subjects, followed by: lingual varices (16.3%), secondary herpes lesions (8.1%), aphthous ulcers (7.9%), fordyce granules (7.2%), frictional keratosis (5%), candidosis (4.9%), fibroepithelial hyperplasia (4.6%), squamous papilloma (3.8%), traumatic ulcers (3.7%), leukoplakia (3.2%), fissured tongue (3.2%), hemangiomas (2.7%), morsicatio buccarum (2.5%), melanin pigmentation (2.5%), lichen planus (2.5%), leukoedema (2.1%), petechiae (1.1%), geographic tongue (1%), actinic cheilitis (0.8%), and erythroplakia (0.1%). Overall, the prevalence of oral mucosal non-malignant lesions was linked to age, gender, diseases, and risk habits. CONCLUSIONS: The high prevalence necessitates adequate awareness of these lesions in the general population. The dental clinicians should also be knowledgeable about the etiopathogenesis, clinical presentation, diagnosis, and treatment of these lesions. PMID- 27374360 TI - Effects of leukocyte-platelet rich fibrin on postoperative complications of direct sinus lifting. AB - BACKGROUND: Blood products have been widely used in soft tissue and bone regeneration in oral and maxillofacial surgery. The purpose of this study is to evaluate the effects of leukocyte-platelet rich fibrin (L-PRF) following direct sinus lifting procedure. METHODS: Twenty-eight patients were included in the study. Direct sinus lifting was performed via lateral window approach under conscious sedation and local anesthesia. Bony window and sinus floor elevation were performed using piezosurgery device. Two groups were formed. In the first group an allogenous bone graft and L-PRF mixture was used as grafting material. The L-PRF membrane was used to close the lateral window. In the second group, only allogenous bone was used for grafting and resorbable collagen membrane was used to close the lateral window. Pain, swelling, sleeping, eating, phonetics, activities of daily living, missed work days and soft tissue healing were evaluated postoperatively. RESULTS: Data of 24 patients were evaluated. Improvements were seen in the studied parameters in the L-PRF group; however, the difference was not significant between the two groups (P>0.05). CONCLUSIONS: The use of L-PRF and allogenous bone graft in combination with L-PRF membrane does not significantly improve postoperative complications following direct sinus lifting. PMID- 27374357 TI - Monoclonal antibody with conformational specificity for a toxic conformer of amyloid beta42 and its application toward the Alzheimer's disease diagnosis. AB - Amyloid beta-protein (Abeta42) oligomerization is an early event in Alzheimer's disease (AD). Current diagnostic methods using sequence-specific antibodies against less toxic fibrillar and monomeric Abeta42 run the risk of overdiagnosis. Hence, conformation-specific antibodies against neurotoxic Abeta42 oligomers have garnered much attention for developing more accurate diagnostics. Antibody 24B3, highly specific for the toxic Abeta42 conformer that has a turn at Glu22 and Asp23, recognizes a putative Abeta42 dimer, which forms stable and neurotoxic oligomers more potently than the monomer. 24B3 significantly rescues Abeta42 induced neurotoxicity, whereas sequence-specific antibodies such as 4G8 and 82E1, which recognizes the N-terminus, do not. The ratio of toxic to total Abeta42 in the cerebrospinal fluid of AD patients is significantly higher than in control subjects as measured by sandwich ELISA using antibodies 24B3 and 82E1. Thus, 24B3 may be useful for AD diagnosis and therapy. PMID- 27374361 TI - Thermographic and clinical evaluation of 808-nm laser photobiomodulation effects after third molar extraction. AB - BACKGROUND: A randomized, blind, controlled clinical study was conducted with a convenience sample of 24 patients to evaluate the effectiveness of an aluminum gallium arsenide (AlGaAs) infrared laser 808 nm after third molar extraction by the use of infrared thermography technique. METHODS: Patients were divided into four groups: erupted third molars were extracted from the patients in Group I and Group II, and impacted third molars were extracted from the patients in Group III and Group IV. Group I and Group III received mock laser therapy in which the device was powered off, and Group II and Group IV were exposed to laser light. Postoperative clinical parameters related to the third molar extraction were evaluated; these parameters included pain, trismus and edema. Circulatory patterns were also evaluated by infrared thermography that exhibited local temperature coefficient at different postoperative periods. RESULTS: A slight improvement was observed for swelling, pain and trismus in patients who received laser irradiation, although the differences were not statistically significant (P>0.05). Laser therapy had a significant influence on the local circulation in the area near the temporomandibular joint, as determined by infrared thermography (P<0.05). CONCLUSIONS: Laser therapy was able to change the local circulation, although it did not significantly influence swelling, pain or trismus during the postoperative period. PMID- 27374362 TI - Vascular endothelial growth factor behavior in different stages of tooth germ development. AB - BACKGROUND: Scientific studies show a possible influence of intercellular and intracellular proteins (VEGF) on the development of physiological and pathological tissue. VEGF, a key regulator of angiogenesis, it would seem essential to take action during the embryonic development of the dental germ. The purpose of the study is to investigate the importance of the enzymatic activity of VEGF through protein quantification at different stages of tooth germ development. METHODS: The quantification of VEGF protein was performed by 3 different laboratory tests: Western-blot analysis, semi-quantitative reverse transcriptase-polymerase chain reaction analysis (RT-PCR) and finally immunohistochemical analysis. Cell cultures of tooth tissue examined are: endothelial cells, stellate reticulum cells, odontoblasts and ameoblast. RESULTS: The VEGF peptide seems to induce an intense cell proliferation, not concomitant with differentiation towards the endothelial line. The expression of VEGF in the inner enamel epithelium (ameloblasts) would seem to depend on the stage of differentiation, leading us to deduce that VEGF and its respective receptor are expressed in dental germ and that induce alterations not only on the vascularization, but also on the inner epithelium activation and then on dental enamel development, respectively on cap and bell stages of embryogenesis. CONCLUSIONS: In our survey, the positive expression of VEGF in all the samples examined, might suggest a fundamental role of angiogenic gene proteins during all stages of embryonic tooth development. It is also characteristic the behavior of stellate reticulum cells, with a significant reduction in VEGF action between early and late stage, which could suggest a possible role of stellate reticulum cells, which would be able to promote and maintain an adequate energy supply to the tissues during early and late stages of differentiation and proliferation. PMID- 27374363 TI - Autofluorescence as indicator for detecting the surgical margins of medication related osteonecrosis of the jaws. PMID- 27374364 TI - BruxApp: the ecological momentary assessment of awake bruxism. PMID- 27374365 TI - Singling Out Intestinal Epithelial Stem Cells. PMID- 27374366 TI - Gemcitabine Activates Natural Killer Cells to Attenuate Pancreatic Cancer Recurrence. PMID- 27374367 TI - Concurrent Lower Gastrointestinal Bleeding Risk and Myocardial Ischemic Risk: Resume Aspirin or Not? PMID- 27374368 TI - The Hydrated Excess Proton in the Zundel Cation H5 O2 (+) : The Role of Ultrafast Solvent Fluctuations. AB - The nature of the excess proton in liquid water has remained elusive after decades of extensive research. In view of ultrafast structural fluctuations of bulk water scrambling the structural motifs of excess protons in water, we selectively probe prototypical protonated water solvates in acetonitrile on the femtosecond time scale. Focusing on the Zundel cation H5 O2 (+) prepared in room temperature acetonitrile, we unravel the distinct character of its vibrational absorption continuum and separate it from OH stretching and bending excitations in transient pump-probe spectra. The infrared absorption continuum originates from a strong ultrafast frequency modulation of the H(+) transfer vibration and its combination and overtones. Vibrational lifetimes of H5 O2 (+) are found to be in the sub-100 fs range, much shorter than those of unprotonated water. Theoretical results support a picture of proton hydration where fluctuating electrical interactions with the solvent and stochastic thermal excitations of low-frequency modes continuously modify the proton binding site while affecting its motions. PMID- 27374370 TI - Movement-related phase locking in the delta-theta frequency band. AB - Movements result from a complex interplay of multiple brain regions. These regions are assembled into distinct functional networks depending on the specific properties of the action. However, the nature and details of the dynamics of this complex assembly process are unknown. In this study, we sought to identify key markers of the neural processes underlying the preparation and execution of motor actions that always occur irrespective of differences in movement initiation, hence the specific neural processes and functional networks involved. To this end, EEG activity was continuously recorded from 18 right-handed healthy participants while they performed a simple motor task consisting of button presses with the left or right index finger. The movement was performed either in response to a visual cue or at a self-chosen, i.e., non-cued point in time. Despite these substantial differences in movement initiation, dynamic properties of the EEG signals common to both conditions could be identified using time frequency and phase locking analysis of the EEG data. In both conditions, a significant phase locking effect was observed that started prior to the movement onset in the delta-theta frequency band (2-7Hz), and that was strongest at the electrodes nearest to the contralateral motor region (M1). This phase locking effect did not have a counterpart in the corresponding power spectra (i.e., amplitudes), or in the event-related potentials. Our finding suggests that phase locking in the delta-theta frequency band is a ubiquitous movement-related signal independent of how the actual movement has been initiated. We therefore suggest that phase-locked neural oscillations in the motor cortex are a prerequisite for the preparation and execution of motor actions. PMID- 27374369 TI - Patterns of postictal cerebral perfusion in idiopathic generalized epilepsy: a multi-delay multi-parametric arterial spin labelling perfusion MRI study. AB - The cerebral haemodynamic status of idiopathic generalized epilepsy (IGE) is a very complicated process. Little attention has been paid to cerebral blood flow (CBF) alterations in IGE detected by arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI). However, the selection of an optimal delay time is difficult for single-delay ASL. Multi-delay multi-parametric ASL perfusion MRI overcomes the limitations of single-delay ASL. We applied multi-delay multi parametric ASL perfusion MRI to investigate the patterns of postictal cerebral perfusion in IGE patients with absence seizures. A total of 21 IGE patients with absence seizures and 24 healthy control subjects were enrolled. IGE patients exhibited prolonged arterial transit time (ATT) in the left superior temporal gyrus. The mean CBF of IGE patients was significantly increased in the left middle temporal gyrus, left parahippocampal gyrus and left fusiform gyrus. Prolonged ATT in the left superior temporal gyrus was negatively correlated with the age at onset in IGE patients. This study demonstrated that cortical dysfunction in the temporal lobe and fusiform gyrus may be related to epileptic activity in IGE patients with absence seizures. This information can play an important role in elucidating the pathophysiological mechanism of IGE from a cerebral haemodynamic perspective. PMID- 27374372 TI - The Nationwide Evaluation of X-Ray Trends, Part 2: US Trends for CT. PMID- 27374371 TI - Genomic imbalance in the centromeric 11p15 imprinting center in three families: Further evidence of a role for IC2 as a cause of Russell-Silver syndrome. AB - Russell-Silver syndrome is a heterogeneous disorder characterized by intrauterine growth retardation, postnatal growth deficiency, characteristic facial appearance, and other variable features. Genetic and epigenetic alterations are identified in about 60% of individuals with Russell-Silver syndrome. Most frequently, Russell-Silver syndrome is caused by altered gene expression on chromosome 11p15 due to loss of methylation at the telomeric imprinting center. To date there have been a handful of isolated clinical reports implicating the centromeric imprinting center 2 in the etiology of Russell-Silver syndrome. Here we report three new families with genomic imbalances, involving imprinting center 2 resulting in gain of methylation at this center and a Russell-Silver syndrome phenotype, including two families with a maternally inherited microduplication and the first pediatric patient with a paternally derived microdeletion. The findings in our families provide additional evidence of a role for imprinting center 2 in the etiology of Russell-Silver syndrome and suggest that imprinting center 2 imprinting abnormalities may be a more common cause of Russell-Silver syndrome than previously recognized. Furthermore, our findings together with previous clinical reports of genomic imbalances involving imprinting center 2 serve to underscore the complexity of the epigenetic regulation of the 11p15 region making it challenging to predict phenotype on the basis of genotype alone. (c) 2016 Wiley Periodicals, Inc. PMID- 27374373 TI - 2016 Residency Match Update and the Golden Opportunity. PMID- 27374374 TI - Telephone Consultation-What Standards Should Apply? PMID- 27374376 TI - Erratum. PMID- 27374375 TI - The Foundation in Evidence of Medical and Dental Telephone Consultations. AB - BACKGROUND: Patients can only make well-informed decisions if the information they are given by health professionals is based on scientific evidence. In this study, we assessed the foundation in evidence of free, publicly available telephone consultations in Germany. METHODS: From March 2013 to January 2014, four hidden clients seeking information asked standardized questions about three medical topics (screening for colorectal cancer, for glaucoma, and for trisomy 21) and three dental ones (the sealing of dental fissures, professional dental cleaning, and mercury detoxification). Depending on the topic, the questions addressed such issues as the risk of disease and the purpose, content, validity, benefits, and risks of potential diagnostic and therapeutic measures. All identifiable telephone consultation services that provided counselling on the above topics were included in the study (23 government-sponsored institutions, 31 institutions independently run by physicians, 521 institutions under religious auspices, 25 dental counselling services). RESULTS: Of the 599 telephone consultation services that were identified, 567 were contacted; 404 did not offer any relevant counselling. A total of 293 conversations were held with the remaining 163 consultation services. Six of these conversations fully met predefined criteria for evidence-based counselling. The percentage of appropriate answers to the key questions on each topic was 5% for colorectal cancer screening (7/140), 23.8% for glaucoma screening (25/105), 33.9% for trisomy 21 screening (121/357), 27.5% for the sealing of dental fissures (28/102), 16.2% for professional dental cleaning (19/117), and 12.9% for mercury detoxification (12/93). The percentage of appropriate answers also varied depending on the type of institution: 26.8% for government-sponsored institutions (67/250), 4.5% for institutions independently run by physicians (4/88), and 31.1% for institutions under religious auspices (82/264). CONCLUSION: The medical and dental counselling now offered over the telephone by the types of institutions included in this study does not satisfy the criteria for evidence-based health information. PMID- 27374378 TI - Additional Investigations. PMID- 27374377 TI - Psychopharmacological Prescriptions in Children and Adolescents in Germany. AB - BACKGROUND: In view of the well-known increase in prescriptions of stimulants for children and adolescents over the last 20 years, it is important to study trends in the prevalence and incidence of the use of other psychotropic drugs by this age group as well, to enable an early response to potential problems in the current care situation. METHODS: We used nationwide data from German statutory health insurance funds (Allgemeine Ortskrankenkasse [AOK], all insurees; Techniker Kranken - kasse [TK], a 50% randomized sample) concerning all insurees aged 0-17 years (5.0 million people in 2012) to study trends in the prevalence and incidence of psychotropic medication use as well as initially prescribing medical specialties over the period 2004-2012, both for the overall group of psychotropic drugs and for selected subgroups of drugs. RESULTS: From 2004 to 2012, the prevalence of psychotropic drug prescriptions (not including herbal and homeopathic substances) for children and adolescents rose from 19.6 to 27.1 per 1000 individuals. Marked rises were seen for stimulants (10.5 to 19.1 per 1000) and antipsychotic drugs (2.3 to 3.1 per 1000), while the prevalence of antidepressant prescriptions remained constant at about 2 per 1000. The rates of new prescriptions from 2006 to 2012 were generally constant or decreasing; for the overall group of (non-herbal, nonhomeopathic) psychotropic drugs, the rate of new prescriptions fell from 9.9 to 8.7 per 1000. There was a trend toward the issuance of new prescriptions by medical specialists, rather than by family physicians and pediatricians. CONCLUSION: The observed increased prevalence of psychotropic drug use among children and adolescents appears to be due not to an increased rate of initial prescriptions for these drugs, but rather to a rise in the number of patients who, once having received such drugs, were given further prescriptions for them in the years that followed. PMID- 27374379 TI - In Reply. PMID- 27374380 TI - Milroy Disease or Primary Congenital Lymphedema Associated With Invasive Squamous Cell Carcinoma. PMID- 27374381 TI - Cutaneous Involvement in the Deep Mycoses: A Literature Review. Part I Subcutaneous Mycoses. AB - The deep mycoses are uncommon in our setting. These fungal infections occur mainly in immunosuppressed patients or in tropical climates, and include subcutaneous infections and systemic infections. The skin is always involved in the former. In the first part of this review, we describe the main subcutaneous mycoses: sporotrichosis, chromoblastomycosis, mycetoma, phaeohyphomycosis, hyalohyphomycosis, and lacaziosis. Early recognition and treatment is important, as these infections are frequently associated with high morbidity. PMID- 27374383 TI - Enterococcus saigonensis sp. nov., isolated from retail chicken meat and liver. AB - Two Gram-stain-positive strains, VE80T and VE116, which were resistant to vancomycin, were isolated from retail chicken meat and liver in Ho Chi Minh, Vietnam, respectively. These strains were characterized by sequence analyses of 16S rRNA, RNA polymerase alpha-subunit (rpoA), ATP synthase alpha-subunit (atpA), and phenylalanyl-tRNA synthase alpha-subunit (pheS) genes, determination of DNA G+C content, cellular fatty acid methyl ester analysis, DNA-DNA hybridization, and conventional morphological and biochemical tests. Strains VE80T and VE116 had 99.6 % 16S rRNA gene sequence similarity with Enterococcus canintestini LMG 13590T, and 99.1 % 16S rRNA gene sequence similarity with Enterococcus dispar ATCC 51266T. However, the two isolates could be clearly differentiated from these reference strains by the low sequence similarities (86.1-86.8 %) of the atpA gene, low DNA-DNA relatedness (<22.8 %), and differences in the production of acid from melezitose and methyl alpha-d-glucoside. Based on the results obtained in the present study, these two isolates are considered to represent a novel species of the genus Enterococcus, for which the name Enterococcus saigonensis sp. nov., is proposed. The type strain is VE80T (=JCM 31193T=CCUG 68827T). PMID- 27374384 TI - Understanding the foot-in-the-door effect as a pseudo-effect from the perspective of the Campbell paradigm. AB - Compliance with a small request (a metaphorical foot-in-the-door) promotes compliance with a subsequent big request. Whereas some explanations expect a drop in the behavioural costs of the big request, others suspect that the effect comes from boosting the underlying attitude. However, evidence for both explanations is equivocal and circumstantial, at best. Drawing on what Kaiser et al. (2010) call the Campbell paradigm, we present an integrative account: Compliance with any request demands a corresponding attitude to counterbalance the costs of the request. In our research, 229 participants were randomly assigned to either a foot-in-the-door (i.e., initially asked to sign a pro-environmental petition) or a control condition. Small-request-compliant participants were more likely than control participants to also comply with the big request and to continue filling out environmental-issues-related questionnaires. However, this foot-in-the-door effect occurred without diminishing behavioural costs or increasing attitude levels. Accordingly, the greater likelihood of small-request-compliant participants to also comply with the big request can be parsimoniously explained by baseline variability in people's attitude levels that manifests in their compliance with the initial request. We conclude that several of the foot-in-the door effects reported in the literature carry the risk of representing mere pseudo-effects. PMID- 27374386 TI - Subclinical zinc deficiency impairs pancreatic digestive enzyme activity and digestive capacity of weaned piglets - CORRIGENDUM. PMID- 27374385 TI - Clinical evaluation of intranasal medetomidine-ketamine and medetomidine-S(+) ketamine for induction of anaesthesia in rabbits in two centres with two different administration techniques. AB - OBJECTIVE: The aim was to compare efficacy and side effects of induction with medetomidine-ketamine or medetomidine-S(+)-ketamine by intranasal (IN) instillation in rabbits and to evaluate both protocols during subsequent isoflurane anaesthesia. STUDY DESIGN: Prospective, blinded, randomized experimental study in two centres. ANIMALS: Eighty-three healthy New Zealand White rabbits undergoing tibial or ulnar osteotomy. METHODS: Medetomidine (0.2 mg kg-1) with 10 mg kg-1 ketamine (MK) or 5 mg kg-1 S(+)-ketamine (MS) was administered IN to each rabbit in a randomized fashion. In Centre 1 (n = 42) rabbits were held in sternal recumbency, and in Centre 2 (n = 41) in dorsal recumbency, during drug instillation. Adverse reactions were recorded. If a rabbit swallowed during endotracheal intubation, half of the initial IN dose was repeated and intubation was re-attempted after 5 minutes. Anaesthesia was maintained with isoflurane. Heart rate, blood pressure, endtidal carbon dioxide concentration and blood gases were recorded. Data were analysed using Student's t test, Mann-Whitney test and Fisher's exact test. RESULTS: In all, 39 animals were assigned to the MK group and 44 to the MS group. Two rabbits in the MS group held in dorsal recumbency died after instillation of the drug. Eight (MK) and 11 rabbits (MS) were insufficiently anaesthetized and received a second IN dose. One rabbit in MK and three in MS required an isoflurane mask induction after the second IN dose. There were no significant differences between treatments for induction, intraoperative data, blood gas values and recovery data. CONCLUSION AND CLINICAL RELEVANCE: This study indicated that medetomidine-ketamine and medetomidine-S(+)-ketamine were effective shortly after IN delivery, but in dorsal recumbency IN administration of S(+)-ketamine led to two fatalities. Nasal haemorrhage was noted in both cases; however, the factors leading to death have not been fully elucidated. PMID- 27374387 TI - [Surgical overview on kidney and pancreas transplantation]. AB - The main purpose of this paper, written by a group of Italian expert transplant surgeons, is to provide clinical support and to help through the decision-making process over pre-transplant surgical procedures in potential kidney recipients, as well as selection of pancreas transplant candidates and perioperative management of kidney recipient. Current topics such as different approaches in minimally invasive donor nephrectomy, methods of graft preservation and treatment of failed allograft were addressed. PMID- 27374388 TI - [Acute Kidney Injury, Type - 3 cardiorenal syndrome, Biomarkers, Renal Replacement Therapy]. AB - Cardiovascular disease and major cardiovascular events represent main cause of death in both acute and chronic kidney disease patients. Kidney and heart failure are common and frequently co-exist This organ-organ interaction, also called organ cross-talk, leads to well-known definition of cardiorenal syndrome (CRS). Here we will describe cardiovascular involvement in patients with acute kidney injury (AKI). Also known as Type-3 CRS or acute reno-cardiac CRS, it occurs when AKI contributes and/or precipitates development of acute cardiac injury. AKI may directly or indirectly produces an acute cardiac event and it can be associated with volume overload, metabolic acidosis and electrolytes disorders such as hyperkalemia and hypocalcemia, coronary artery disease, left ventricular dysfunction and fibrosis which has been also described in patients with AKI with the consequence of direct negative effects on cardiac performance. PMID- 27374389 TI - [Quality end of life in uremic patients: theory and practice]. AB - The rate of fragile elderly patients affected by chronic kidney disease stage 5 5D is rapidly increasing. The decision making process regarding the start and the withdrawal of dialysis is often difficult for all those involved: patients, relatives, nephrologists and renal nurses. Therefore nephrologists and renal nurses are called to rapidly improve their theoretical and practical competence about the end-of-life care. The quality of clinical intervention and management requires a sound expertise in the ethical, legal, organizational and therapeutic aspects, not trivial nor even deductible from purely private and individual opinions nor from traditional medical practice. The present paper discusses the ethical and legal implications related to the start rather than to withdrawn from dialysis, preferring a non-dialysis medical treatment and / or palliative care. Operational aspects regarding the regional network of palliative care, the path of shared decision making process and a systematic approach to optimize medical and nursing interventions through the Liverpool Care Pathway program are discussed thereafter. PMID- 27374390 TI - [Cystinic nephrolythiasis: clinical experience and new diagnostic and therapeutic perspectives]. AB - Cystinuria is an inherited autosomal recessive disease with a prevalence 1:7000 and typical age of onset in the second decade of life. This nephrolithiasis is not always well known and well studied and for this reason it is often underdiagnosed. Cystinuria is characterized by increased urinary excretion of cystine and dibasic amino acids (lysine, ornithine, arginine) caused by defective transport of these amino acids across the luminal membrane of proximal tubule and small intestine cells. Two mutated genes responsible of this tubular defect are SLC3A1 on chromosome 2 and SLC7A9 on chromosome 19. Clinical manifestations of cystinuria are essentially those related to stones formation and their movement across the urinary tract, like flank pain/abdomen pain and hematuria, as occurred in other nephrolithiasis types. Diagnosis is based on biochemical urine analysis, stone analysis and imaging. Genetic study of this disease may be a new and stimulating approach to better understand the defects and identify new therapeutic targets. A wider knowledge and a more detailed approach to cystinuria may help to ameliorate patients quality of life, to prevent recurrences and complications and to develop more specific and adequate treatments. PMID- 27374391 TI - [Italian Registry Dialysis and Transplant 2011-2013]. AB - The Italian Registry of Dialysis and Transplantation (RIDT) has recently resumed the collection of data of patients on RRT in Italy. Data were requested to Regional Registries for the years 2011-2013 and they contributed according to their possibilities. Eighteen Regions or autonomous Provinces provided data with various degrees of completeness and this made possible to bridge the gap between the current and the previous census (referring to 2010). RESULTS: Incidencedata were associated to a sample with a coverage of 77% of the national population (46/60 million inhabitants). Patients who started dialysis in these three years were, respectively, 168, 166 and 160 patients pmp. If we project this data to the national population is reasonable to think that 9500-10000 patients per year start the dialytic treatment. PREVALENCE: The prevalence of patients on dialysis in Italy range, in the 10 years of RIDT, between 750 and 825 patients pmp. Based on this we can reasonably estimate that in Italy there are 45-49000 dialysis patients. Incidence and prevalence vary widely in different regions. Mortalityon dialysis in Italy during the period 2011-2013 was on average 16.2 per 100 patient years (95% CI: 16.1-16.7) with regional variation smaller than that observed in incidence and prevalence. CONCLUSIONS: In this paper, data analysis are presented in a direct and non comparative manner. However, it provides information on the status of the RRT in Italy and the temporal consistency of the data is a proof of their validity. Registry data were published in the official site of Italian Registry that can be reached through the website of SIN (www.sin-italy.org). PMID- 27374392 TI - [Metformin and kidney]. AB - Metformin is the first choice among drugs used for the treatment of type II diabetes mellitus mainly because of several advantages: proven hypoglycemic effect, good safety profile, virtually no risk of hypoglycemia, body weight reduction, lipid-lowering effect, efficacy in preventing micro- and macrovascular complications as well as adverse cardiac and cerebrovascular events and reduced cost. Previous reports had shown an increased risk of lactic acidosis in patients receiving metformin. However, the current Guidelines have greatly limited this risk to certain categories of patients, such as those with severe chronic renal failure, particularly when predisposing risk factors such as administration of iodinated contrast are present. In this review, we reported the main data of the literature on the use of metformin in patients with chronic renal failure and both highly expected benefits and high potential risks. PMID- 27374393 TI - Quality of life of hemodialysis patients in Central and Southern Italy: cross sectional comparison between Hemodiafiltration with endogenous reinfusion (HFR) and Bicarbonate Hemodialysis. AB - INTRODUCTION: in hemodialysis (HD) patients, poor health-related quality of life (HR-QoL) is prevalent and associated with adverse outcomes. HR-QoL is strictly linked to nutritional status of HD patients. Hemodiafiltration with endogenous reinfusion (HFR) is an alternative dialysis technique that combines diffusion, convection and absorption. It reduces burden of inflammation and malnutrition and this effect may cause beneficial effect on HR-QoL. However no data on HR-QoL in HFR is currently available. METHODS: we designed a cross-sectional multicentre study in order to compare the HR-QoL in patients treated with HFR versus Bicarbonate HD (BHD). We enrolled adult patients HFR treated for at least 6 months, with life expectancy greater than six months and without overt cognitive deficit. The recruited patients in HFR were matched for age, gender, dialytic vintage and performance in activities of daily living (Barthel index) with BHD treated patients. SF-36 questionnaire for the assessment of HR-QoL was administered. RESULTS: one hundred fourteen patients (57 HFR vs 57 BHD) were enrolled (age 65.413.5 years; dialysis vintage 5.4 (3.3-10.3) years; 53% males) from 18 dialysis non-profit centres in central and southern Italy. As result of matching, no difference in age, gender, dialytic age and Barthel index was found between HFR and BHD patients. In HFR patients we observed better values of physical component score (PCS) of SF-36 than BHD patients (P=0.048), whereas no significant difference emerged in the mental component score (P=0.698). In particular HFR patients were associated with higher Physical Functioning (P=0.045) and Role Physical (P=0.027). CONCLUSIONS: HFR is associated with better physical component of HR-QoL than BHD, independently of age, gender, dialysis vintage and invalidity score. Whether these findings translate into a survival benefit must be investigated by longitudinal studies. PMID- 27374394 TI - [Lithium poisoning: neurological signs, nephrological therapy]. AB - Lithium is an effective drug in the treatment of bipolar disorder and other psychiatric and neurological diseases. Unfortunately, its therapeutic index is narrow. There are three types of lithium poisoning: acute poisoning (in untreated patients), acute on chronic poisoning, when an overdose is taken accidentally or with suicidal intent, in patients under treatment and chronic poisoning (patient treated with lithium) when drug intake is correct but excessive in relation to its elimination (increased dose or more often reduced clearance) resulting in lithium overload. In this last condition, the clinical presentation is primary neurological while therapy involves the nephrologist provided that lithium clearance is mainly renal and hemodialysis is the most effective method for removal. PMID- 27374395 TI - [Nonconvulsive status epilepticus due to Fentanyl intoxication in hemodialysed patients: two case reports and review of the literature]. AB - The management of the pain therapy (ischemic pain, neoplastic pain) in hemodialysis patients has become a frequent challenge in the last years. These patients often require the prescription of major analgesic drugs such as Opioids like Fentanyl, in order to control the pain. It is necessary to pay attention to the correct dosage and to the half life of these drugs, that results prolonged in the chronic renal insufficiency. The main side effect of opioids is respiratory depression which is well known, however, up to date, there is a lack of reports about other less frequent side effects, such as epilepsy or status epilepticus, in the literature. We report two cases of chronic hemodialysed patients who developed a generalized nonconvulsive status epilepticus secondary to Fentanyl intoxication administered for the pain therapy. These cases required a synergic team management with involvement of the nephrologist, the neurologist and the intensivist. The generalized non convulsive status epilepticus could be an important and serious side effect of Fentanyl in hemodialysis patients and it is therefore necessary a close monitoring of the pain therapy in these subjects. PMID- 27374396 TI - [Nephrology: knowledge and digital memory]. AB - Mathematical sciences have had a huge development with the use of numbers, which is used to process images, sounds and computer languages. Medical knowledge is collected in databases in text format (groups of words). So far, words in Medicine have never been processed and we are not currently able to create connections between them in any way. With mathematical logic, words can be treated as numbers. Words, using logical connectives, become more and more calculable and developable with the support of mathematical and computer sciences. The words in medicine may have the same development of the numbers in mathematical sciences. Words that belong to the history of the patient, physical examinations and clinical data can be gathered in tables, therefore, they can be made available to computer applications, creating a digital memory by presenting it as required by the doctor. The author believes that the clinical reasoning of the Doctor uses connectives available in mathematical logic. Therefore, thought can be supported by mathematical calculation. Knowledge engineering programs will develop data return or self-generated algorithms, up to the future use of artificial intelligence in the field of nephrology. PMID- 27374397 TI - [Healthcare patient loyalty]. AB - If the "old economy" preached standardization of products/services in order to reduce costs, the "new economy" is based on the recognition of the needs and the management of information. It is aimed at providing better and more usable services. One scenario is a national health service with regional management but based on competition between hospitals/companies.This led to a different handling of the user/patient, which has become the center of the health system: marketing seeks to retain the patient, trying to push a client-patient to not change their healthcare service provider. In costs terms, it is more economical to retain a customer rather than acquire a new one: a satisfied customer is also the best sounding board for each company. Customer equity is the management of relations with patients which can result in a greater customer value: it is possible to recognize an equity of the value, of the brand and of the report. Loyalty uses various marketing activities (basic, responsive, responsible, proactive and collaborative): each hospital/company chooses different actions depending on how many resources it plans to invest in loyalty. PMID- 27374398 TI - Assessment of Referral and Chemotherapy Treatment Patterns for Elderly Patients With Non-small-Cell Lung Cancer. AB - BACKGROUND: Physiologic changes of aging in combination with greater comorbidity could lead to treatment nihilism for elderly patients (>= 70 years old) with non small-cell lung cancer (NSCLC). Randomized trials have shown improved survival with chemotherapy since 1999, but it remains unclear whether these data have translated into practice. PATIENTS AND METHODS: We conducted a retrospective, population-based cohort study of NSCLC cases diagnosed in Ontario, Canada from 2000 to 2010. We compared referral and treatment patterns among patients aged < 70 versus >= 70 years. Multivariable analyses evaluated predictors of referral to medical oncology or treatment with chemotherapy. RESULTS: Of 61,646 patients with NSCLC, 32,131 (52.1%) were >= 70 years. Fewer adenocarcinomas were diagnosed in the elderly (29.8% vs. 44%), and more elderly patients lacked microscopic confirmation of malignancy (20.1% vs. 6.2%). Charlson co-morbidity scores >= 2 (14.0% vs. 7.4%) were higher in the elderly. Only 59.5% of elderly patients with NSCLC were referred to a medical oncologist, versus 78.5% of younger patients. Elderly patients were less likely to receive chemotherapy (18.3% vs. 46.7%), even among those referred to a medical oncologist (30.1% vs. 58.6%). Neither referral nor treatment changed substantially over time. The elderly also had a shorter median survival (5.8 vs. 9.6 months); however, there was less difference in median survival (13.6 vs. 14.9 months) among patients receiving chemotherapy. CONCLUSION: Elderly patients are less likely to be considered for systemic therapy for NSCLC, and evidence of benefit has had minimal impact on practice. We believe this disparity could be improved through systematically using tools to comprehensively assess elderly patients. PMID- 27374399 TI - The ecology of an adaptive radiation of three-spined stickleback from North Uist, Scotland. AB - There has been a large focus on the genetics of traits involved in adaptation, but knowledge of the environmental variables leading to adaptive changes is surprisingly poor. Combined use of environmental data with morphological and genomic data should allow us to understand the extent to which patterns of phenotypic and genetic diversity within a species can be explained by the structure of the environment. Here, we analyse the variation of populations of three-spined stickleback from 27 freshwater lakes on North Uist, Scotland, that vary greatly in their environment, to understand how environmental and genetic constraints contribute to phenotypic divergence. We collected 35 individuals per population and 30 abiotic and biotic environmental parameters to characterize variation across lakes and analyse phenotype-environment associations. Additionally, we used RAD sequencing to estimate the genetic relationships among a subset of these populations. We found a large amount of phenotypic variation among populations, most prominently in armour and spine traits. Despite large variation in the abiotic environment, namely in ion composition, depth and dissolved organic Carbon, more phenotypic variation was explained by the biotic variables (presence of predators and density of predator and competitors), than by associated abiotic variables. Genetic structure among populations was partly geographic, with closer populations being more similar. Altogether, our results suggest that differences in body shape among stickleback populations are the result of both canalized genetic and plastic responses to environmental factors, which shape fish morphology in a predictable direction regardless of their genetic starting point. PMID- 27374400 TI - VirusMapper: open-source nanoscale mapping of viral architecture through super resolution microscopy. AB - The nanoscale molecular assembly of mammalian viruses during their infectious life cycle remains poorly understood. Their small dimensions, generally bellow the 300nm diffraction limit of light microscopes, has limited most imaging studies to electron microscopy. The recent development of super-resolution (SR) light microscopy now allows the visualisation of viral structures at resolutions of tens of nanometers. In addition, these techniques provide the added benefit of molecular specific labelling and the capacity to investigate viral structural dynamics using live-cell microscopy. However, there is a lack of robust analytical tools that allow for precise mapping of viral structure within the setting of infection. Here we present an open-source analytical framework that combines super-resolution imaging and naive single-particle analysis to generate unbiased molecular models. This tool, VirusMapper, is a high-throughput, user friendly, ImageJ-based software package allowing for automatic statistical mapping of conserved multi-molecular structures, such as viral substructures or intact viruses. We demonstrate the usability of VirusMapper by applying it to SIM and STED images of vaccinia virus in isolation and when engaged with host cells. VirusMapper allows for the generation of accurate, high-content, molecular specific virion models and detection of nanoscale changes in viral architecture. PMID- 27374401 TI - Spontaneous loss of a co-twin and the risk of birth defects after assisted conception. AB - The study of very early pregnancy loss is impractical in the general population, but possible amongst infertility patients receiving carefully monitored treatments. We examined the association between fetal loss and the risk of birth defects in the surviving co-twin in a retrospective cohort study of infertility patients within an infertility clinic in South Australia from January 1986 to December 2002, linked to population registries for births, terminations and birth defects. The study population consisted of a total of 5683 births. Births from singleton pregnancies without loss were compared with survivors from (1) pregnancies with an empty fetal sac at 6-8 weeks after embryo transfer, (2) fetal loss subsequent to 8-week ultrasound and (3) multiple pregnancy continuing to birth. Odds ratios (OR) for birth defects were calculated with adjustment for confounders. Amongst infertility patients, the prevalence of birth defects was 7.9% for all twin pregnancies without fetal loss compared with 14.6% in pregnancies in which there had been an empty sac at ultrasound, and 11.6% for pregnancies with fetal loss after 6-8 weeks. Compared with singleton pregnancies without loss, the presence of an empty sac was associated with an increased risk of any defect (OR=1.90, 95% confidence intervals (CI)=1.09-3.30) and with multiple defects (OR=2.87, 95% CI=1.31-6.28). Twin pregnancies continuing to birth without loss were not associated with an overall increased prevalence of defects. We conclude that the observed loss of a co-twin by 6-8 weeks of pregnancy is related to the risk of major birth defects in the survivor. PMID- 27374402 TI - Pretreatment of spent sulphite liquor via ultrafiltration and nanofiltration for bio-based succinic acid production. AB - Ultrafiltration and nanofiltration of spent sulphite liquor (SSL) has been employed to evaluate the simultaneous production of lignosulphonates and bio based succinic acid using the bacterial strains Actinobacillus succinogenes and Basfia succiniciproducens. Ultrafiltration with membranes of 10, 5 and 3kDa molecular weight cut-off results in significant losses of lignosulphonates (26 50%) in the permeate stream, while nanofiltration using membrane with 500Da molecular weight cut-off results in high retention yields of lignosulphonates (95.6%) in the retentate stream. Fed-batch bioreactor cultures using permeates from ultrafiltrated SSL resulted in similar succinic acid concentration (27.5g/L) and productivity (0.4g/L/h) by both strains. When permeates from nanofiltrated SSL were used, the strain B. succiniciproducens showed the highest succinic acid concentration (33.8g/L), yield (0.58g per g of consumed sugars) and productivity (0.48g/L/h). The nanofiltration of 1t of thick spent sulphite liquor could lead to the production of 306.3kg of lignosulphonates and 52.7kg of succinic acid, whereas the ultrafiltration of 1t of thick spent sulphite liquor using a 3kDa membrane could result in the production of 237kg of lignosulphonates and 71.8kg of succinic acid when B. succiniproducens is used in both cases. PMID- 27374403 TI - Versatility of chemically synthesized guide RNAs for CRISPR-Cas9 genome editing. AB - The CRISPR-Cas9 system has become the most popular and efficient method for genome engineering in mammalian cells. The Streptococcus pyogenes Cas9 nuclease can function with two types of guide RNAs: the native dual crRNA and tracrRNA (crRNA:tracrRNA) or a chimeric single guide RNA (sgRNA). Although sgRNAs expressed from a DNA vector are predominant in the literature, guide RNAs can be rapidly generated by chemical synthesis and provide equivalent functionality in gene editing experiments. This review highlights the attributes and advantages of chemically synthesized guide RNAs including the incorporation of chemical modifications to enhance gene editing efficiencies in certain applications. The use of synthetic guide RNAs is also uniquely suited to genome-scale high throughput arrayed screening, particularly when using complex phenotypic assays for functional genomics studies. Finally, the use of synthetic guide RNAs along with DNA-free sources of Cas9 (mRNA or protein) allows for transient CRISPR-Cas9 presence in the cell, thereby resulting in a decreased probability of off-target events. PMID- 27374404 TI - Developing strategies to increase plasmid DNA production in Escherichia coli DH5alpha using batch culture. AB - Plasmid DNA (pDNA) production has recently increased as a result of advances in DNA vaccines. The practical development of pDNA vaccines requires high yield and productivity of supercoiled plasmid DNA (sc-pDNA). The yield and productivity are influenced by the host strain, the plasmid, the production process, and especially by growth conditions, such as the culture type and medium. We evaluated different strategies to increase pDNA production by Escherichia coli DH5alpha in batch culture. The strategies were driven by the development of a four single-factor experimental design and were based on the change of culture media composition in terms of carbon and nitrogen and the modification of the pH control by using NaOH or NH4OH. The results revealed the carbon (50g/L of glycerol) and nitrogen (8.34g/L of YESP) concentration in the culture medium and starting pH control with NH4OH when most of the organic nitrogen was consumed. Under these conditions, we obtained a volumetric yield of 213mg pDNA/L, a specific yield of 10mg pDNA/g DCW (dry cell weight), 92% of sc-pDNA and a productivity of 17.6mg pDNA/(Lh). The pDNA productivities reached were 42% higher than the productivities reported by other authors applying similar conditions. PMID- 27374405 TI - Flavanone and isoflavone glucosylation by non-Leloir glycosyltransferases. AB - Flavonoids possess a wide range of biological activities. Their glycosylation is of considerable interest, as it often positively influences their pharmacokinetic and other molecular properties. We recently showed that two non-Leloir glycosyltransferases that use sucrose as carbohydrate donor, an amylosucrase from Neisseria polysaccharea (Ams-Np) and a glucansucrase from Streptococcus oralis (GtfR-So), were hardly able to glucosylate flavones, but accepted flavanes as substrates. We now examined compounds from two other flavonoid classes, flavanones and isoflavones for glucose transfer by these enzymes. Taxifolin was investigated as a flavanone analogue of both, the accepted pentahydroxyflavane catechin and the non-accepted pentahydroxyflavone quercetin. It was glucosylated by both enzymes, but much better by GtfR-So than by Ams-Np due to apparent strong inhibition of the latter. The acceptance of a collection of isoflavones strongly depended on the substitution pattern of the core. Only two of the 10 compounds examined yielded glucosides in satisfactory amounts. With these substrates, both enzymes catalyzed formation of a range of products, differing in the number of saccharide units. The structures of mono- and diglycosylated compounds obtained in higher amounts were elucidated. While GtfR-So attached glucose to taxifolin in the B ring at O4', both enzymes glucosylated the isoflavones in the A ring at O7. All products were alpha-glucosides. Interglycosidic linkages formed by Ams-Np were alpha1-4. To our knowledge, this is the first report of glucosylation of flavanone and isoflavone aglycones by an amylosucrase. All characterized compounds have not previously been described. PMID- 27374406 TI - Essential Role of the PfRh5/PfRipr/CyRPA Complex during Plasmodium falciparum Invasion of Erythrocytes. AB - Plasmodium falciparum parasites in the merozoite stage invade human erythrocytes and cause malaria. Invasion requires multiple interactions between merozoite ligands and erythrocyte receptors. P. falciparum reticulocyte binding homolog 5 (PfRh5) forms a complex with the PfRh5-interacting protein (PfRipr) and Cysteine rich protective antigen (CyRPA) and binds erythrocytes via the host receptor basigin. However, the specific role that PfRipr and CyRPA play during invasion is unclear. Using P. falciparum lines conditionally expressing PfRipr and CyRPA, we show that loss of PfRipr or CyRPA function blocks growth due to the inability of merozoites to invade erythrocytes. Super-resolution microscopy revealed that PfRipr, CyRPA, and PfRh5 colocalize at the junction between merozoites and erythrocytes during invasion. PfRipr, CyRPA, and PfRipr/CyRPA/PfRh5-basigin complex is required for triggering the Ca(2+) release and establishing the tight junction. Together, these results establish that the PfRh5/PfRipr/CyRPA complex is essential in the sequential molecular events leading to parasite invasion of human erythrocytes. PMID- 27374407 TI - Cross-Species Interferon Signaling Boosts Microbicidal Activity within the Tick Vector. AB - Evolution of hematophagy in blood-sucking parasites likely involves communication with their hosts. We find that Ixodes ticks are responsive to IFNgamma acquired in a blood meal from mice infected with the Lyme disease-causing bacteria Borrelia burgdorferi, leading to induction of antimicrobial responses. Ixodes ticks parasitizing B. burgdorferi-infected mice upregulated an I. scapularis Rho like GTPase (IGTPase). IGTPase knockdown enhanced B. burgdorferi levels in post fed ticks, suggesting this protein controls spirochete survival. Notably, IGTPase was only induced during pathogen acquisition from mice and not upon transmission to naive hosts. Microinjection of ticks with IFNgamma induced IGTPase, and ticks parasitizing IFNgamma knockout mice, failed to upregulate IGTPase. Additionally, ticks lacking the transcription factor STAT, which signals downstream of IFNgamma, did not induce IGTPase. IGTPase expression induced antimicrobial peptides, including Dae2, previously shown to inhibit B. burgdorferi. These results identify an interspecies signaling cascade allowing ticks to detect invading bacteria and mount microbicidal responses. PMID- 27374408 TI - Detection of spatial change points in the mean and covariances of multivariate simultaneous autoregressive models. AB - In this paper, we propose a test procedure to detect change points of multidimensional autoregressive processes. The considered process differs from typical applied spatial autoregressive processes in that it is assumed to evolve from a predefined center into every dimension. Additionally, structural breaks in the process can occur at a certain distance from the predefined center. The main aim of this paper is to detect such spatial changes. In particular, we focus on shifts in the mean and the autoregressive parameter. The proposed test procedure is based on the likelihood-ratio approach. Eventually, the goodness-of-fit values of the estimators are compared for different shifts. Moreover, the empirical distribution of the test statistic of the likelihood-ratio test is obtained via Monte Carlo simulations. We show that the generalized Gumbel distribution seems to be a suitable limiting distribution of the proposed test statistic. Finally, we discuss the detection of lung cancer in computed tomography scans and illustrate the proposed test procedure. PMID- 27374409 TI - Employing biomarkers of healthy ageing for leveraging genetic studies into human longevity. AB - Genetic studies have thus far identified a limited number of loci associated with human longevity by applying age at death or survival up to advanced ages as phenotype. As an alternative approach, one could first try to identify biomarkers of healthy ageing and the genetic variants associated with these traits and subsequently determine the association of these variants with human longevity. In the present study, we used this approach by testing whether the 35 baseline serum parameters measured in the Leiden Longevity Study (LLS) meet the proposed criteria for a biomarker of healthy ageing. The LLS consists of 421 families with long-lived siblings of European descent, who were recruited together with their offspring and the spouses of the offspring (controls). To test the four criteria for a biomarker of healthy ageing in the LLS, we determined the association of the serum parameters with chronological age, familial longevity, general practitioner-reported general health, and mortality. Out of the 35 serum parameters, we identified glucose, insulin, and triglycerides as biomarkers of healthy ageing, meeting all four criteria in the LLS. We subsequently showed that the genetic variants previously associated with these parameters are significantly enriched in the largest genome-wide association study for human longevity. In conclusion, we showed that biomarkers of healthy ageing can be used to leverage genetic studies into human longevity. We identified several genetic variants influencing the variation in glucose, insulin and triglycerides that contribute to human longevity. PMID- 27374410 TI - Novel mutations in one allele in a Chinese family with neurofibromatosis type 1: Including a complex insertion-deletion mutation. AB - Neurofibromatosis type 1 (NF1) is a hereditary disease with variable clinical manifestations. This study was performed in a Chinese three-generation family containing two members with NF1. Two novel mutations, c.853_854insTC and c.1975_1976delinsTA, were identified in the same allele in both patients by direct sequencing. By reverse transcription polymerase chain reaction, we found that the NF1 transcript contained the first mutation instead of the second mutation, suggesting a pathological role of c.853_854insTC mutation. Case reports of patients with two NF1 mutations in the same allele have not been reported. Our findings expand the known spectrum of NF1 mutations and the ongoing recognition of different mutations may give insight into the mysterious NF1 pathogenesis. PMID- 27374412 TI - Uncovering the factors associated with skeletal muscle weakness in interstitial lung disease. PMID- 27374413 TI - Predictors of death among cardiac arrest patients after therapeutic hypothermia: A non-tertiary care center's initial experience. AB - INTRODUCTION AND OBJECTIVES: Therapeutic hypothermia (TH) is recommended for patients with return of spontaneous circulation (ROSC) after cardiac arrest (CA). There is still uncertainty about management, target temperature and duration of TH. In the present study we aim to describe the initial experience of a non tertiary care center with TH after CA and to determine predictors of mortality. METHODS: During the period 2011-2014, out of 2279 patients hospitalized in the intensive care unit, 82 had a diagnosis of CA with ROSC. We determined predictors of mortality and neurological outcome in comatose patients with ROSC after CA treated by TH. RESULTS: A total of 15 patients were included, mean age 47.3+/-14 years, 10 (67.0%) male. CA occurred out-of-hospital (n=11; 73.3%) or in-hospital (n=4; 26.7%), in initial shockable (n=10; 66.7%) or non-shockable (n=5, 33.3%) rhythm. The mean time from CA to ROSC (CA-ROSC) was 44.7+/-36.5 min. All patients met the 24-hour TH target temperature of 33 degrees C. The mean neuron-specific enolase (NSE) level was 93.7+/-109.0 MUg/l. Seven patients (46.7%) were discharged with good cerebral performance and eight (53.3%) died. Patients who survived had lower median age (p=0.032), shorter CA-ROSC (p=0.048), lower NSE levels (p=0.020) and initial ventricular fibrillation rhythm (p=NS). CONCLUSIONS: The effectiveness of TH appears to be related to younger age, shockable initial rhythm and shorter CA-ROSC time. This results indicates some lines of inquiry that should be developed in appropriate prospective studies. The role of biomarkers as predictors of prognosis is an open question, with NSE potentially playing an important role. PMID- 27374414 TI - Acute kidney injury in acute coronary syndromes - An important multifactorial consequence. AB - INTRODUCTION: Acute kidney injury (AKI) is a pathological phenomenon with a negative impact on outcomes in different clinical scenarios. Its mechanism in acute coronary syndrome (ACS) is not completely understood, and measures to prevent it are not uniform. We set out to study the incidence, clinical relevance, predictors and possible implications for patient management of AKI in ACS. METHODS: Using data from a multicenter national registry on ACS, we retrospectively analyzed predictors of AKI and its impact on outcomes (in hospital complications and one-year mortality). All ACS types were included. AKI was defined as an increase in serum creatinine of >=0.3 mg/dl (>=26.4 MUmol/l) and/or by >=1.5 times baseline. RESULTS: A total of 7808 ACS patients were included in the analysis, 1369 (17.5%) of whom developed AKI. AKI was shown to be an independent predictor of in-hospital major bleeding (odds ratio [OR] 2.09; 95% confidence interval [CI] 1.19-3.64; p=0.01), mortality (OR 4.72; 95% CI 2.94 7.56; p<0.001) and one-year mortality (hazard ratio 2.01; 95% CI 1.51-2.68; p<0.001). The incidence of AKI was associated with older age, history of hypertension, renal failure and stroke/transient ischemic attack, Killip class >1 on admission and left ventricular ejection fraction <50%. Performance of coronary angiography or angioplasty were not associated with AKI. Diuretics during admission were predictors of AKI only in patients in Killip class 1. CONCLUSIONS: AKI is an important finding in ACS, with a significant impact on hard clinical endpoints such as in-hospital and one-year mortality. It is associated with easily identifiable clinical factors and an invasive strategy does not increase its incidence. PMID- 27374415 TI - Improving Resident Communication in the Intensive Care Unit. The Proceduralization of Physician Communication with Patients and Their Surrogates. AB - Effective communication between providers and patients and their surrogates in the intensive care unit (ICU) is crucial for delivery of high-quality care. Despite the identification of communication as a key education focus by the American Board of Internal Medicine, little emphasis is placed on teaching trainees how to effectively communicate in the ICU. Data are conflicting on the best way to teach residents, and institutions vary on their emphasis of communication as a key skill. There needs to be a cultural shift surrounding the education of medical residents in the ICU: communication must be treated with the same emphasis, precision, and importance as placing a central venous catheter in the ICU. We propose that high-stakes communications between physicians and patients or their surrogates must be viewed as a medical procedure that can be taught, assessed, and quality controlled. Medical residents require training, observation, and feedback in specific communication skill sets with the goal of achieving mastery. It is only through supervised training, practice in real time, observation, and feedback that medical residents can become skillful practitioners of communication in the ICU. PMID- 27374416 TI - Heat processing of peanut seed enhances the sensitization potential of the major peanut allergen Ara h 6. AB - SCOPE: Processing of food has been shown to impact IgE binding and functionality of food allergens. In the present study, we investigated the impact of heat processing on the sensitization capacity of Ara h 6, a major peanut allergen and one of the most potent elicitors of the allergic reaction. METHODS AND RESULTS: Peanut extracts obtained from raw or heat-processed peanut and some fractions thereof were biochemically and immunochemically characterized. These extracts/fractions, purified Ara h 6, or recombinant Ara h 6 including Ara h 6 mutants lacking disulfide bridges were used in in vitro digestion tests and mouse models of experimental sensitization. Peanut roasting led to the formation of complexes of high molecular weight, notably between Ara h 6 and Ara h 1, which supported the induction of IgE specific to native Ara h 6. On the contrary, a fraction containing free monomeric 2S albumins or purified native Ara h 6 displayed no intrinsic allergenicity. In addition to complex formation, heat denaturation and/or partial destabilization enhanced Ara h 6 immunogenicity and increased its sensitivity to digestion. CONCLUSION: These results suggest that sensitization potency and IgE binding capacity can be supported by different structures, modified and/or produced during food processing in interaction with other food constituents. PMID- 27374417 TI - Fertilization-independent Cell-fusion between the Synergid and Central Cell in the Polycomb Mutant. AB - In flowering plants, fertilization of the central cell gives rise to an embryo nourishing endosperm. Recently, we reported that the endosperm absorbs the adjacent synergid cell through a cell-fusion, terminating the pollen tube guidance by a rapid inactivation of the synergid cell. Although this synergid endosperm fusion (SE fusion) initiates soon after fertilization, it was still unknown whether the triggers of SE fusion are stimuli during fertilization or other seed developmental processes. To further dissect out the SE fusion process, we investigated the SE fusion in an Arabidopsis mutant defective for MULTICOPY SUPPRESSOR OF IRA1 (MSI1), a subunit of the polycomb repressive complex 2 (PRC2). The mutant msi1 develops autonomous endosperm without fertilization. Time-lapse imaging revealed a rapid efflux of the synergid contents during the autonomous endosperm development, indicating that the initiation of SE fusion is under the control of some of the events triggered by fertilization of the central cell distinct from the discharge of pollen tube contents and plasma membrane fusion. PMID- 27374418 TI - Space charge limited release of charged inverse micelles in non-polar liquids. AB - Charged inverse micelles (CIMs) generated during a continuous polarizing voltage between electrodes in the model system of polyisobutylene succinimide in dodecane do not populate a diffuse double layer like CIMs present in equilibrium (regular CIMs), but instead end up in interface layers. When the applied voltage is reversed abruptly after a continuous polarizing voltage step, two peaks are observed in the transient current. The first peak is due to the release of regular CIMs from the diffuse double layers formed during the polarizing voltage step, which is understood on the basis of the Poisson-Nernst-Planck equations. The second peak is due to the release of a small fraction of generated negative CIMs from the interface layer. A model based on space charge limited release of the generated negative CIMs from the interface layer is presented and the results of the model are compared with several types of measurements. For the situation in which the bulk is deprived of regular CIMs and neutral inverse micelles, the results of the model are in agreement with the experimental results. However, for the situation in which regular CIMs and neutral inverse micelles are present, the model shows discrepancies with the experiment for high voltages and high charge contents. These discrepancies are attributed to electrohydrodynamic flow caused by local variations in the electric field at the vicinity of the electrodes, which occur during the reversal voltage. Also the long term decrease of the amount of released generated CIMs is studied and it is found that the presence of regular CIMs and neutral inverse micelles speeds up the decrease. This study provides a deeper insight in the electrodynamics of CIMs and is relevant for various applications in non-polar liquids. PMID- 27374419 TI - Dynamic nanoproteins: self-assembled peptide surfaces on monolayer protected gold nanoparticles. AB - Here, we demonstrate the formation of dynamic peptide surfaces through the self assembly of small peptides on the surface of monolayer protected gold nanoparticles. The complexity of the peptide surface can be simply tuned by changing the chemical nature of the added peptides and the ratio in which these are added. The dynamic nature of the surface permits adaptation to changes in the environment. PMID- 27374420 TI - Estimating subthreshold tumor on MRI using a 3D-DTI growth model for GBM: An adjunct to radiation therapy planning. AB - Mathematical modeling and serial magnetic resonance imaging (MRI) used to calculate patient-specific rates of tumor diffusion, D, and proliferation, rho, can be combined to simulate glioblastoma multiforme (GBM) growth. We showed that the proportion and distribution of tumor cells below the MRI threshold are determined by the D/rho ratio of the tumor. As most radiation fields incorporate a 1-3 cm margin to account for subthreshold tumor, accurate characterization of subthreshold tumor aids the design of optimal radiation fields. This study compared two models: a standard one-dimensional (1D) isotropic model and a three dimensional (3D) anisotropic model using the advanced imaging method of diffusion tensor imaging (DTI) - with regards to the D/rho ratio's effect on the proportion and spatial extent of the subthreshold tumor. A validated reaction-diffusion equation accounting for tumor diffusion and proliferation modeled tumor concentration in time and space. For the isotropic and anisotropic models, nine tumors with different D/rho ratios were grown to a T1 radius of 1.5 cm. For each tumor, the percent and extent of tumor cells beyond the T2 radius were calculated. For both models, higher D/rho ratios were correlated with a greater proportion and extent of subthreshold tumor. Anisotropic modeling demonstrated a higher proportion and extent of subthreshold tumor than predicted by the isotropic modeling. Because the quantity and distribution of subthreshold tumor depended on the D/rho ratio, this ratio should influence radiation field demarcation. Furthermore, the use of DTI data to account for anisotropic tumor growth allows for more refined characterization of the subthreshold tumor based on the patient-specific D/rho ratio. PMID- 27374421 TI - 'Working in the dark': Swedish general dental practitioners on the complexity of root canal treatment. AB - AIM: To explore elements of reasoning and understanding that might obstruct the performance of good-quality root canal treatment (RCT) and make general dental practitioners (GDPs) produce and accept root fillings of inferior quality. METHODOLOGY: The study was designed as a qualitative and explorative study based on seven videotaped focus group interviews analysed by means of qualitative content analysis. Nine predetermined questions were followed. Thirty-three GDPs (4-6 dentists/interview), employed in the Public Dental Health Service in Gothenburg, Sweden, participated. RESULTS: Feelings such as anxiety, frustration, stress or exhaustion were associated with RCT. In general, RCT was regarded as complex, mysterious and embedded in uncertainty. A feeling of loss of control was frequently described in relation to all procedural steps from negotiating the canal to prognostic deliberations. Reasons could include challenging canals, complicated instruments and the fact that treatment had to be performed in a concealed space without visible insight. Several dentists questioned the requirements for correctly performing RCT, and some indicated that striving towards optimal technical root filling quality should not be expected in each case in general practice. Most of the GDPs were unable to complete a case within the remuneration system, and they therefore either spent more time than the set fee allowed for or accepted a suboptimal root filling when the time limit was reached. CONCLUSIONS: High levels of stress and frustration in relation to RCT were reported by the GDPs. RCT was regarded as complex and was often performed with an overall sense of lack of control. PMID- 27374422 TI - Culture of domestic cat ovarian tissue in vitro and in the chick embryo chorioallantoic membrane. AB - In vitro culture and transplantation procedures are essential protocols employed in the evaluation of ovarian follicle survival and development. Culture in the chorioallantoic membrane (CAM) of chick embryos is an intermediate method that provides important follicle development information and has not been tested for cat ovaries to date. The aim of this study was to investigate if in vitro and CAM culture could be used as short-term systems to study cat ovarian tissue development. The ovaries of eight cats were dissected into 3-mm(3) cubes, cultured in vitro and in CAM for up to 5 days, and stained with hematoxylin-eosin and Gomori trichrome. Cell proliferation was analyzed using anti-Ki67. Possible differences among groups were investigated by analysis of variance or the Kruskal Wallis test followed by Bonferroni correction. The T-test or Wilcoxon test was used to verify differences between the CAM and IVC. Results revealed that 87.5% of all follicles were primordial during culture. The percentage of primordial follicles in the morphologically normal follicles (MNF) pool was always higher than 80%, with the exception of Day 3 of CAM culture, but the number of MNF reduced significantly from Day 0 (600 out of 777 follicles) to Day 5 in the CAM (91 out of 171) and IVC (296 out of 686). The number of primordial follicles in 1 mm(3) in Days 2, 3, and 5 in the CAM was significantly lower than that in the control (Day 0). No cellular proliferation was observed in culture. Vascularization occurred in the CAM culture, but with no association to follicular viability. In addition, both methods showed an increase in connective tissue during culture. Although no significant differences were observed in the percentage of MNF, there was a reduction in the total number of follicles, both for IVC and CAM-cultured ovarian tissue. Furthermore, anti-Ki67 did not stain any follicle after Day 0 in IVC or in CAM culture. Neither system was capable of promoting follicle growth and/or development. The results show that the CAM is not a suitable system for feline ovarian tissue and highlight the necessity to improve IVC systems in cats. PMID- 27374423 TI - Effect of dietary fish oil supplementation on ram semen freeze ability and fertility using soybean lecithin- and egg yolk-based extenders. AB - Ram semen cryopreservation is not efficient for artificial insemination in commercial herds. Beneficial effects of dietary fish oil have been evaluated for cryopreservation of ram semen in soybean lecithin (SL) and egg yolk (EY)-based extenders. A factorial study (two diets * two extenders) was used to analyze the effects of two diets supplemented with fish oil (n-3 fatty acid) or palm oil (saturated fatty acids; [SFAs]) to freeze ram semen in two extenders containing SL or EY. Motility characteristics, membrane integrity, abnormal morphology, mitochondria activity, acrosome integrity, apoptotic status, and fertilizing ability were assessed after freeze-thawing. Although diet had significant (P <= 0.05) effects on the quality parameters of frozen-thawed sperm, effects of extenders on these traits were not significant (P > 0.05). The higher significant (P <= 0.05) percentage of total motility and progressive motility were observed in n-3/SL (44.83 +/- 1.56 and 28.33 +/- 1.4) and n-3/EY (43.33 +/- 1.56 and 28.50 +/- 1.4) than SFA/SL (32.16 +/- 1.56 and 14.00 +/- 1.4) and SFA/EY (31.66 +/- 1.56 and 12.66 +/- 1.4) groups. Moreover, n-3/SL and n-3/EY produced the higher significant (P <= 0.05) percentage of membrane integrity of sperm (39.83 +/- 1.4 and 37.33 +/- 1.4) than SFA/SL and SFA/EY (29.83 +/- 1.4 and 28.5 +/- 1.4). For viability results, the higher significant percentage of live sperm was observed in n-3/SL and n-3/EY (43.16 +/- 1.38 and 45.66 +/- 1.38) than SFA/SL and SFA/EY (28.66 +/- 1.38 and 27.5 +/- 1.38). For fertility trials, n-3-based diets (n-3/SL and n-3/EY) improved significantly (P <= 0.05) pregnancy rate (44% and 46%), parturition rate (42% and 42%), and lambing rate (46% and 44%) compared with the SFA-based diets (SFA/SL and SFA/EY). No interaction effects have been found between diets and extenders (P > 0.05). It seems that dietary fish oil can improve the semen performance after freezing-thawing process and artificial insemination aside from type of extenders. PMID- 27374424 TI - Expression and localization of angiopoietin family in buffalo ovarian follicles during different stages of development and modulatory role of angiopoietins on steroidogenesis and survival of cultured buffalo granulosa cells. AB - The present study investigated the expression and localization of angiopoietin (ANPT) family members in buffalo ovarian follicles of different size. It also looked at the role of ANPTs in estradiol secretion and mRNA expression of phosphoinositide-3-kinase-protein kinase B signaling pathway cellular proliferation (phosphoinositide-dependant kinase and protein kinase B [AKT]) and proapoptotic (BAD) factors with caspase 3 in cultured buffalo granulosa cells (GCs). The mRNA and protein expression of ANPT-1 was greatest (P < 0.05), whereas ANPT-2 was reduced (P < 0.05) in preovulatory follicles as compared to F1 follicle. Tyrosine kinase with immunoglobulin-like and EGF-like domains 1 transcripts and protein expression did not change in all follicular groups, whereas tyrosine kinase with immunoglobulin-like and EGF-like domains 2 mRNA was highest (P < 0.05) in theca interna but not GC layer of preovulatory follicle. All members of ANPT family were localized in GC and theca interna showing a stage specific immunoreactivity. Cultured GCs were treated with ANPT-1 and ANPT-2 separately at doses of 1, 10, and 100 ng/mL and in combination at 100 ng/mL for three incubation periods (24, 48, and 72 hours). Estradiol secretion was highest (P < 0.05) at 100 ng/mL at 72 hours of incubation when GCs were treated with either protein alone. The mRNA expression of phosphoinositide-dependant kinase and AKT was highest (P < 0.05), and BAD with caspase 3 was lowest (P < 0.05) at 100 ng/mL at 72 hours of incubation, when cultured GCs were treated separately with each protein or in combination. The immuoreactivity of AKT, pAKT, and pBAD were maximal, whereas BAD was minimal with 100 ng/mL at 72 hours when cultured GCs treated with either protein alone. The findings indicate that ANPTs are expressed in a regulated manner in buffalo ovarian follicle during different stages of development where they may promote steroidogenesis and GC survival through autocrine and paracrine actions. PMID- 27374425 TI - Well-differentiated fetal adenocarcinoma of the lung mimicking adenoid cystic carcinoma on fine needle aspiration: A case report. AB - Well-differentiated fetal adenocarcinoma (WDFA) of the lung is a rare variant of adenocarcinoma with an unusual morphology. Although the histologic features of this rare neoplasm have been well established, there is a deficit in the literature with regards to its discrete cytomorphologic features. We report the fine needle aspiration (FNA) findings of a case of this unusual malignancy in a 44-year-old man with an incidental lung nodule. FNA revealed three-dimensional clusters of epithelial cells with scant cytoplasm, hyperchromatic nuclei that are associated with an extracellular metachromatic matrix. The original cytology report was signed out as an epithelial neoplasm favor adenoid cystic carcinoma. Consequently, a wedge resection of the lung was done and the histologic diagnosis was WDFA of the lung. The findings of minimal nuclear atypia in association with focally abundant spheres of extracellular matrix can mimic adenoid cystic carcinoma. WDFA has good prognosis and therefore, pre-operative cytologic diagnosis is critical to clinical management. We present the cytomorphologic features of this neoplasm with particular emphasis on a potential diagnostic pitfall of this rare entity. Diagn. Cytopathol. 2016;44:917-920. (c) 2016 Wiley Periodicals, Inc. PMID- 27374426 TI - Memory impairment due to fipronil pesticide exposure occurs at the GABAA receptor level, in rats. AB - Fipronil (F) a pesticide considered of second generation cause various toxic effects in target and non-target organisms including humans in which provoke neurotoxicity, having the antagonism of gamma-amino butyric acid (GABA) as their main mechanism for toxic action. GABAergic system has been involved in processes related to the memory formation and consolidation. The present work studied the importance of GABA to the mechanisms involved in the very early development of fipronil-induced memory impairment in rats. Memory behavior was assessed using new object recognition task (ORT) and eight radial arm maze task (8-RAM) to study effects on cognitive and spatial memory. Locomotor behavior was assessed using open field task (OF). The dose of fipronil utilized was studied through a pilot experiment. The GABA antagonist picrotoxin (P) was used to enhance fipronil effects on GABAergic system. Fipronil or picrotoxin decrease memory studied in ORT and 8-RAM tasks. Additionally, F and P co-exposure enhanced effects on memory compared to controls, F, and P, suggesting strongly a GABAergic effect. Weight gain modulation and fipronil in blood were utilized as animal's intoxication indicators. In conclusion, here we report that second-generation pesticides, such as fipronil, can have toxic interactions with the CNS of mammals and lead to memory impairment by modulating the GABAergic system. PMID- 27374427 TI - Cognitive function, stress hormones, heart rate and nutritional status during simulated captivity in military survival training. AB - Stress influences numerous psychological and physiological processes, and its effects have practical implications in a variety of professions and real-world activities. However, few studies have concurrently assessed multiple behavioral, hormonal, nutritional and heart-rate responses of humans to acute, severe stress. This investigation simultaneously assessed cognitive, affective, hormonal, and heart-rate responses induced by an intensely stressful real-world environment designed to simulate wartime captivity. Sixty males were evaluated during and immediately following participation in U.S. Army Survival, Evasion, Resistance, and Escape (SERE) school, three weeks of intense but standardized training for Soldiers at risk of capture. Simulated captivity and intense mock interrogations degraded grammatical reasoning (p<0.005), sustained-attention (p<0.001), working memory (p<0.05) and all aspects of mood assessed by the Profile of Mood States (POMS) questionnaire: Tension/Anxiety, Depression/Dejection, Anger/Hostility, Vigor/Activity, Fatigue/Inertia; Confusion/Bewilderment, and Total Mood Disturbance (p<0.001) It also elevated heart rate (p<0.001); increased serum and salivary cortisol and dehydroepiandrosterone-sulfate (DHEA-s) (p<0.01); elevated serum epinephrine, norepinephrine, and soluble transferrin receptors (sTfR) (p<0.01); increased salivary neuropeptide-Y (NPY) (p<0.001); and decreased serum prolactin and serum and salivary testosterone (p<0.001). Partial recovery was observed immediately after training, but stress-induced changes, particularly in body weight and several of the biomarkers, persisted. This study demonstrates that when individuals were exposed to realistic and controlled simulated captivity, cognition, mood, stress hormones, nutritional status and heart rate are simultaneously altered, and each of these subsequently recovers at different rates. PMID- 27374428 TI - Vascular assessment of wound healing: a clinical review. AB - Although macrovascular screening of patients with chronic wounds, particularly in the lower extremities, is accepted as part of clinical practice guidelines, microvascular investigation is less commonly used for a variety of reasons. This can be an issue because most patients with macrovascular disease also develop concomitant microvascular dysfunction. Part of the reason for less comprehensive microvascular screening has been the lack of suitable imaging techniques that can quantify microvascular dysfunction in connection with non-healing chronic wounds. This is changing with the introduction of fluorescence microangiography. The objective of this review is to examine macro- and microvascular disease, the strengths and limitations of the approaches used and to highlight the importance of microvascular angiography in the context of wound healing. PMID- 27374429 TI - Erratum to Loboda et al. "Carbon monoxide: pro- or anti-angiogenic agent? Comment on Ahmad et al. (Thromb Haemost 2015; 113: 329-337). AB - [This corrects the article DOI: 10.1160/TH15-01-0082.]. PMID- 27374430 TI - Potent Glycosidase Inhibition with Heterovalent Fullerenes: Unveiling the Binding Modes Triggering Multivalent Inhibition. AB - Glycosidases are key enzymes in metabolism, pathogenic/antipathogenic mechanisms and normal cellular functions. Recently, a novel approach for glycosidase inhibition that conveys multivalent glycomimetic conjugates has emerged. Many questions regarding the mechanism(s) of multivalent enzyme inhibition remain unanswered. Herein we report the synthesis of a collection of novel homo- and heterovalent glyco(mimetic)-fullerenes purposely conceived for probing the contribution of non-catalytic pockets in glysosidases to the multivalent inhibitory effect. Their affinities towards selected glycosidases were compared with data from homovalent fullerene conjugates. An original competitive glycosidase-lectin binding assay demonstrated that the multivalent derivatives and the substrate compete for low affinity non-glycone binding sites of the enzyme, leading to inhibition by a "recognition and blockage" mechanism. Most notably, this work provides evidence for enzyme inhibition by multivalent glycosystems, which will likely have a strong impact in the glycosciences given the utmost relevance of multivalency in Nature. PMID- 27374431 TI - Parkin loss-of-function pathology: Premature neuronal senescence induced by high levels of reactive oxygen species? AB - Parkinson's and Alzheimer's diseases (PD and AD, respectively) are considered to be diseases of advanced brain ageing, which seems to involve high levels of reactive oxygen species (ROS). AD neurodegeneration is initially apparent in the hippocampus; as AD progresses, many more brain regions are affected. PD associated neurodegeneration is relatively limited to dopaminergic neurons of the substantia nigra pars compacta (SNpc), especially in cases in which patients inherit particular disease-causing mutations. Thus, the task of elucidating mechanisms by which loss of function of one particular protein triggers death of a subset of neurons may be more approachable. Understanding the mechanisms of neurodegeneration in these forms of PD may not only shed light on avenues leading toward therapeutic strategies in PD and other neurodegenerative diseases, but also on those leading toward understanding natural ageing. Neurodegeneration in PD patients harboring homozygous loss-of-function mutations in the PARK2 gene may result from unbalanced levels of ROS, which are mostly produced in mitochondria and can irreparably damage macromolecules and trigger apoptosis. This review discusses mitochondrial sources of ROS, how ROS can trigger apoptosis, mechanisms by which Parkin loss-of-function may cause neurodegeneration by increasing ROS levels, and concludes with hypotheses regarding selective SNpc dopaminergic neuron vulnerability. PMID- 27374432 TI - Immune related transcriptional responses and performance of Litopenaeus vannamei post-larvae fed on dietary probiotic PrimaLac((r)). AB - The present study investigated the effects of various levels of multi-strain probiotic on the immune related gene expression, digestive enzyme activity, growth performance, body chemical composition and survival of Litopenaeus vannamei post-larvae. After transferring post-larvae of L. vannamei to indoor conditions and subsequent acclimation to laboratory condition for 14 days, the shrimp were fed multi-strain probiotic at four different doses of 0, 0.25, 0.5 and 1.0 g kg(-1) for eight weeks. Shrimp fed 0.5 and 1.0 g kg(-1) probiotic PrimaLac((r)) exhibited significantly (p < 0.05) higher weight gain, specific growth rate, body crude protein as well as lower FCR compared to other groups. Feeding on 0.5 and 1 g kg(-1) dietary multi-strain probiotic significantly (p < 0.05) increased the level of body crude protein. Oral administration of 0.5 and 1.0 g kg(-1) multi-strain probiotic significantly (p < 0.05) decreased body crude lipid and body moisture respectively. 30 days after feeding, protease, amylase and lipase activity increased in groups fed 0.5 and 1.0 g kg(-1) probiotic PrimaLac((r)). However, on the 60th day, specific protease and amylase activity in all treatment groups were significantly higher than control group (p < 0.05) but lipase activity was higher (p < 0.05) in groups fed 0.5 and 1.0 g kg(-1) multi-strain probiotic. Oral administration of 1.0 g kg(-1) probiotic increased (p < 0.05) the level of prophenoloxidase and g-type lysozyme gene on day 30th and 60th after treatment. On day 30th and 60th, penaeidin gene expression was significantly higher in all treatment groups compared to the control group (p < 0.05). In general, findings of this study demonstrated that oral administration of 0.5 and 1.0 g kg(-1) multi-strain probiotic improved the performance of the fish and increased the expression of immune related genes. PMID- 27374433 TI - Functional features of hemocyte subpopulations of the invasive mollusk species Dreissena polymorpha. AB - Dreissena polymorpha is a mussel species that invaded many lotic and lentic inland waters in Western Europe and North America. Its positive or negative interactions with biotic and abiotic components of ecosystems are numerous, making this bivalve the subject of numerous studies in ecology, ecophysiology and ecotoxicology. In these contexts, the functional characterization of the zebra mussel hemocytes is of particular interest, as hemocytes are central cells involved in vital functions (immunity, growth, reproduction) of molluscan physiology. Dreissena polymorpha circulating hemocytes populations were characterized by a combination of structural and functional analysis. Assessments were performed during two contrasted physiological periods for mussels (gametogenesis and spawning). Three hemocyte types were identified as hyalinocytes and blast-like cells for agranular hemocytes and one granulocyte population. Flow cytometry analysis of hemocytes functionalities indicated that blast-like cells had low oxidative and mitochondrial activities and low lysosomal content. Hyalinocytes and granulocytes are fully equipped to perform innate immune response. Hyalinocytes exhibit higher oxidative activity than granulocytes. Such observation is not common since numerous studies show that granulocytes are usually cells that have the highest cellular activities. This result demonstrates the significant functional variability of hemocyte subpopulations. Moreover, our findings reveal that spawning period of Dreissena polymorpha was associated with an increase of hyalinocyte percentage in relation to low levels of biological activities in hemocytes. This reduction in hemocyte activity would reflect the important physiological changes associated with the spawning period of this invasive species known for its high reproductive potential. PMID- 27374434 TI - CsPTX1, a pentraxin of Cynoglossus semilaevis, is an innate immunity factor with antibacterial effects. AB - Pentraxin 1 (PTX1) is a member of the pentraxin protein family, which plays important roles in the innate immunity of vertebrates. In fish, the biological function of PTX1 is essentially unknown. In this study, we examined the expression and function of a PTX homologue (CsPTX1) from the tongue sole, Cynoglossus semilaevis. CsPTX1 contains 223 amino acids and shares 49.3%-38.8% overall sequence identity with other known fish pentraxins. CsPTX1 is expressed in multiple tissues and is upregulated by bacterial and viral infection. CsPTX1 contains a pentraxin domain, which is known to bind extracellular antigens, and recombinant CsPTX1 (rCsPTX1) bound a wide range of Gram-positive and Gram negative bacteria. rCsPTX1 also agglutinated all the bacteria tested in a Ca(2+) dependent manner and the agglutinating capacity of rCsPTX1 was abolished in the absence of calcium. As well as its ability to agglutinate bacterial cells, rCsPTX1 displayed apparent bacteriostatic activity against Pseudomonas fluorescens in vitro by influencing the permeability of the microbial envelope. When introduced in vivo, rCsPTX1 enhanced the host's resistance to bacterial infection. These results indicate that CsPTX1 is a classic pattern recognition molecule that defends C. semilaevis against bacterial infection. PMID- 27374435 TI - Lab on a stick: multi-analyte cellular assays in a microfluidic dipstick. AB - A new microfluidic concept for multi-analyte testing in a dipstick format is presented, termed "Lab-on-a-Stick", that combines the simplicity of dipstick tests with the high performance of microfluidic devices. Lab-on-a-stick tests are ideally suited to analysis of particulate samples such as mammalian or bacterial cells, and capable of performing multiple different parallel microfluidic assays when dipped into a single sample with results recorded optically. The utility of this new diagnostics format was demonstrated by performing three types of multiplex cellular assays that are challenging to perform in conventional dipsticks: 1) instantaneous ABO blood typing; 2) microbial identification; and 3) antibiotic minimum inhibitory (MIC) concentration measurement. A pressure balance model closely predicted the superficial flow velocities in individual capillaries, that were overestimated by up to one order of magnitude by the Lucas Washburn equation conventionally used for wicking in cylindrical pores. Lab-on-a stick provides a cost-effective, simple, portable and flexible multiplex platform for a range of assays, and will deliver a new generation of advanced yet affordable point-of-care tests for global diagnostics. PMID- 27374436 TI - Melatonin and pro-hypnotic effectiveness of the antidepressant Trazodone: A preliminary evaluation in insomniac mood-disorder patients. PMID- 27374437 TI - [Association between serum levels of S100A8/S100A9 and clinical features of colorectal cancer patients]. AB - OBJECTIVE: To analyze the association between serum levels of S100A8/S100A9 and clinicopathological features of colorectal cancer patients.? METHODS: A total of 82 patients with CRC and 14 healthy controls were enrolled for this study. The levels of S100A8 and S100A9 in serum were detected by ELISA assay. The association between S100A8/S100A9 and clinicopathological features was analyzed by student-t test and one-way ANOVA. Receiver Operating Characteristic curve was used to analyze diagnostic efficiency of serum S100A8 and S100A9 for colon rectal cancer. Logistic regression model was also established to analyze the possible risk factors for elevation of S100A8/S100A9.? RESULTS: The levels of S100A8 and S100A9 were (1 403.3+/-593.7) and (2 890.3+/-994.9) pg/mL in patients with colon cancer, and (712.8+/-265.3) and (1 492.7+/-564.6) pg/mL in controls, respectively, with significant difference between the two groups (P<0.01). The similar results were found in rectal cancer patients, with a level of S100A8 and S100A9 at (1 417.7+/-666.5) and (3 026.7+/-887.6) pg/mL, respectively. Diagnostic sensitivity and specificity of S100A8 and S100A9 are better than traditional biomarkers. The levels of S100A9 in serum of CRC patients were correlated with clinical stages and distant metastasis. Serum levels of S100A9 in patients of stage III [(3 111.9+/-178.5) pg/mL] and stage IV [(3 831.4+/-278.5) pg/mL] were significantly (P<0.01) higher than that in stage I [(2 276.1+/-167.4) pg/mL], whereas there was significant change in S100A8 levels. Logistic regression showed the possible risk factors for the elevation of S100A9, including depth of invasion, lymphatic metastasis and degree of differentiation (P<0.05).? CONCLUSION: Serum level of S100A8 and S100A9 in CRC patients were significantly increased and serum level of S100A9 was positively correlated with the malignant features of CRC. PMID- 27374438 TI - [Expression of two transcript variants of long noncoding RNA C6orf176 in non small cell lung cancer and its clinical significance]. AB - OBJECTIVE: To explore two transcript variants expression of long noncoding RNA C6orf176 in non-small cell lung cancer (NSCLC) and the clinical pathological significance. ? METHODS: The expressions of transcript variant 1 (TV1) and transcript variant 2 (TV2) of long noncoding RNA C6orf176 in 57 NSCLC and adjacent cancerous tissues were examined by qPCR with beta-actin as internal control.? RESULTS: Based on the results of qPCR, for C6orf176-TV1, 42 cases were down-regulated and 15 cases were up-regulated. The C6orf176-TV1 level was correlated to the grade of differentiation (P<0.05) but it was not correlated with gender, age, smoking history, tumor type and TNM stage. The expression of C6orf176-TV1 had a potential value in diagnosis of NSCLC by receiver operator characteristic (ROC) curve. Area under curve (AUC) of ROC curve was 0.708 (95% CI 0.615 to 0. 802). The sensitivity and specificity were 51% and 88%, respectively. For C6orf176-TV2, 39 cases were down-regulated and 18 cases were up-regulated. The C6orf176-TV2 level was correlated with the grade of differentiation (P<0.05) but it was not correlated with gender, age, tumor size, smoking history and TNM stage. C6orf176-TV2 level had value in diagnosis of NSCLC by ROC curve. AUC of ROC curve was 0.64 (95% CI 0.531 to 0.749). The sensitivity and specificity were 49% and 75%, respectively. Of the 57 specimens, 53 cases were simultaneous up or down-regulation of C6orf176-TV1 and C6orf176-TV2. The correlation coefficient was 0.99.? CONCLUSION: The expression of C6orf176-TV1 or C6orf176-TV2 is down regulated in NSCLC and it is correlated with the grade of differentiation. It may act as a diagnosis indicator for NSCLC patients. PMID- 27374439 TI - [Y-27632 reduces the MMP2 and MMP9 expression in endothelial cell via inhibition of ROCK signal pathway]. AB - OBJECTIVE: To explore the effect of ROCK inhibitor Y-27632 on the matrix metalloproteinase 2 and 9 (MMP2 and MMP9) gene expression and activity in tumor necrosis factor alpha (TNF-alpha)-treated human umbilical vein endothelial cell (HUVEC).? METHODS: HHUVEC was divided into 3 groups, a control group, a TNF-alpha group, and a TNF-alpha plus Y-27632 group. The expressions of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), MMP2 and MMP9 were examined by real-time PCR. The MMP2/9 activity was measured by gelatin zymography.? RESULTS: Compared to the control group, the mRNA expressions of ICAM-1, VCAM-1, MMP2 and MMP9 were increased TNF-alpha-treated cells, which were suppressed by ROCK inhibitor (P<0.01). The MMP2/9 activity was elevated in TNF-alpha-treated cells, which was reversed by ROCK inhibitor (P<0.05).? CONCLUSION: ROCK inhibitor can suppress TNF-alpha-induced inflammation in endothelial cells through down-regulation of MMP2/9. PMID- 27374440 TI - [Autophagy in hippocampal nerve cells from rats with sepsis-associated encephalopathy]. AB - OBJECTIVE: To show evidence of the autophagy in hippocampal nerve cells from rats with sepsis-associated encephalopathy (SAE) in vivo and to investigate the expression of microtubule-associated protein 1 light chain 3 (LC3). ? METHODS: A rat model of sepsis was established by the cecal ligation and puncture (CLP). A total of 60 male Wistar rats (30 days old) were randomly divided into a sham group (n=10) and a CLP group (n=50). At 12 hours after CLP, the electroencephalogram (EEG) and somatosensory evoked potential (SEP) changes in rats were monitored and the neurobehavioral score was measured. According to the occurrence of SAE, the CLP group was further divided into an SAE(+) group and an SAE(-) group. Histopathological changes in hippocampus were observed by hematoxylin-eosin staining. An electron microscope was used to observe autophagosome formation and lysosome activation in the hippocampal nerve cells. Expressions of LC3-I and LC3-II protein were measured by Western blot. ? RESULTS: Five of 50 rats in CLP group died in 12 hours after CLP. According to the low neurobehavioral score and abnormal EEG and SEP, 16 rats were diagnosed as SAE. The incidence of SAE was 35.56% (16/45). Compared with the sham group or the SAE( ) group, the frequency of alpha wave in SAE(+) group was significantly decreased at 12 hours after CLP, the delta wave increased, the P1 amplitude decreased, and the latency of SEP waves (P1 and N1) was prolonged (P<0.05). The morphology of hippocampal nerve cells was obvious in a status of edema. Pyramidal cells decreased significantly, even dissolved, and cell arrangement was in disorder in the SAE(+) group. But these cells were normal in the sham group and the SAE(-) group. The structure of hippocampal nerve cells was disordered, and the autophagy, granular matrix and square or rectangular crystals were found in the SAE(+) group. However, there was no autophagy both in the sham group and the SAE( ) group. LC3-II/LC3-I ratio in the hippocampal nerve cells was increased significantly at 12 hours after CLP in the SAE(+) group when compared with that in the sham or the SAE(-) group (P<0.05). ? CONCLUSION: There is autophagy in hippocampal nerve cells from rats with SAE and the LC3-II/LC3-I ratio is increased significantly. PMID- 27374441 TI - [Role of DNA methyltransferases in the pathogenesis of neuropathic pain in rats]. AB - OBJECTIVE: To explore the role of DNA methyltransferases (DNMTs) in the pathogenesis of neuropathic pain (NPP) in rats following sciatic nerve chronic constriction injury (CCI).? METHODS: A total of 27 adult male Sprague-Dawley rats with successful implantation of lumbar intrathecal catheter were randomly divided into 3 groups: a sham + normal saline group (sham+NS group), a CCI+NS group, and a CCI+5-azacytidine group (CCI+5-AZA group) (n=9 in each group). The rats in the Sham+NS group and the CCI+NS group received NS, while the rats in the CCI+5-AZA group received 10 MUmol/L of 5-AZA (a DNMTs inhibition) once a day through spinal injection from the 3th day to 14th day after CCI surgery. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of ipsilateral hinds in the 3 groups were measured before or at the 3th, 5th, 7th, 10th or 14th day after CCI surgery. At the end of experiments, all rats were killed under deep anesthesia and their lumbar spinal cords were dissected to examine the DNMT1, DNMT3a and DNMT3b expression by RT-PCR, Western blot and immunohistochemistry, respectively.? RESULTS: Compared with the sham+NS group, the MWT and TWL in the CCI+NS group were obviously reduced from the 3th day to the 14th day after surgery (both P<0.05). Compared with the CCI+NS group, the MWT and TWL in the CCI+5-AZA group were obviously increased from the 5th day to the 14th day after surgery (both P<0.05), but they were still reduced compared with the sham+NS group (both P<0.05). The DNMT1, DNMT3a and DNMT3b were highly expressed in the lumbar spinal dorsal horn in all rats, and the positive signals were mainly located in the nucleus. The DNMT1, DNMT3a and DNMT3b levels in the CCI+NS group were increased significantly compared with that in the sham+NS group on the 14th day after surgery (all P<0.05). The DNMT1, DNMT3a and DNMT3b expressions in the CCI+ 5-AZA group were decreased significantly compared with that in the CCI+NS group (all P<0.05), but they still increased compared with that in the sham+NS group (all P<0.05). ? CONCLUSION: Up-regulation of DNMTs in the lumbar spinal may play an important role in the pathogenesis of NPP in CCI rats. DNMTs inhibitors (5-AZA) could reduce expression of DNMTs and attenuate CCI-induced NPP, which might be a potential therapeutic drug for NPP. PMID- 27374442 TI - [Effect of parecoxib on hippocampal inflammation and memory function in aged rats after splenectomy]. AB - OBJECTIVE: To explore the effect of parecoxib on hippocampal inflammation and short-term memory function after splenectomy in aged rats.? METHODS: A total of 90 aged male SD rats were randomly divided into 9 groups (all n=10): a control group (Group C), an anesthesia day 1 group (A1 group), an operation day 1 group (O1 group), a saline day 1 group (S1 group), a parecoxib day 1 group (P1 group), an anesthesia day 3 group (A3 group), an operation day 3 group (O3 group), a saline day 3 group (S3 group), and a parecoxib day 3 group (P3 group). In the A1 group and A3 group, rats were anesthetized by intraperitoneal injection of pentobarbital sodium. Under anesthesia condition, rats in the O1 group and O3 group underwent splenectomy. One hour before splenectomy, rats in the P1 group and P3 group received parecoxib injection of 10 mg/kg via tail vein. In the S1 group and S3 group, rats received the same dose of saline. The rats were trained for 5 days in shuttle box before anesthesia, surgery and drug treatment. After shuttle box test, the rats were killed at postoperative 1 and 3 d. The hippocampus was isolated to measure the CD11b expression by immunofluorescent staining, and TNF-alpha, IL-1 and COX-2 mRNA expression by RT-PCR.? RESULTS: Compared with the Group C, the electric shock time was increased in the O1 and O3 groups, but the active escape time was shortened and the active avoidance reaction (AAR) was decreased (all P<0.01). Compared with the O1 or O3 group, the electric shock time was shortened, the active escape time and AAR was increased in the P1 or P3 group (all P<0.05). There were more CD11b positive cells and TNF alpha, IL-1beta, COX-2 mRNA expression in hippocampus in the O1, O3, S1 or S3 group compared with the Group C (all P<0.01). Both CD11b positive cells and TNF alpha, IL-1beta, COX-2 mRNA expression were decreased in the P1 or P3 group compared with that in the O1 or O3 group (all P<0.01). ? CONCLUSION: The parecoxib could reduce hippocampal inflammation and improve short-term memory function through the inhibition of COX-2 expression in aged rats after splenectomy. PMID- 27374443 TI - [Comparison between treadmill exercise test and stress-rest myocardial perfusion imaging in myocardial bridge with symptoms]. AB - OBJECTIVE: To evaluate the feature and difference between treadmill exercise test (TET) and myocardial perfusion imaging (MPI) in myocardial bridge patients with symptoms.? METHODS: The data from 97 patients, who underwent 256-slice CT coronary angiography (CTCA) on TET and MPI, were collected and analyzed retrospectively. The patients were divided into an incomplete MB group (n=41) and a complete MB group (n=56). They were also divided into three groups according to the narrow degree of mural coronary artery (MCA) during the cardiac systolic period (Nobel grade): a Nobel 1 grade group (n=44), a Nobel 2 grade group (n=42), and a Nobel 3 grade group (n=11). Besides, the abnormal TET and MPI patients were divided into a TET abnormal group (n=21) and a MPI abnormal group (n=31). The results of TET and MPI were compared among the total, the different MB type groups and the different Noble grade groups, while the complete MB thickness and length were also compared between the abnormal TET group and the MPI abnormal group.? RESULTS: The positive rate of MPI (39/97) was higher than that of TET (26/97) in total (chi2=8.048, P<0.01). But there was no significant difference in the positive rate of TET (5/41) and MPI (8/41) in the incomplete group (chi2=1.000, P>0.05). There was a significant difference in the positive rate of TET (21/56) and MPI (31/56) in the complete MB group (chi2=8.333, P<0.01). There were significant difference in the positive rate of TET (6/44) and MPI (12/44) in the Noble 1 grade group (chi2=4.500, P<0.05), or TET (11/42) and MPI (18/42) in the Nobel 2 grade group (chi2=5.444, P<0.05). But there was no difference in Nobel 3 grade group (P>0.05). The complete MB thickness was (3.4+/-0.6) and (2.9+/-0.8) mm between the TET abnormal group and the MPI abnormal group, with statistically difference (t=2.229, P<0.05). But the MB length was (16.6+/-5.5) and (15.7+/-7.1) mm, with no statistical difference (t=0.489, P>0.05).? CONCLUSION: MPI is more sensitive than TET in myocardial ischemia in patients with MB, especially to complete MB and mild-to-moderate systolic narrowing of MCA. The positive rate is low to incomplete MB, and it is highly sensitive to severe systolic narrowing of MCA. There is difference in the MB thickness between the two methods, but there is no difference in the MB length between the two methods. PMID- 27374444 TI - [Changes in P-wave, T-wave, and ST segment amplitude in 12 lead electrocardiogram in children with breath holding spell]. AB - OBJECTIVE: To explore the change of the amplitude of P wave, T wave and ST segment of 12 lead electrocardiogram (ECG) in children with breath holding spell.? METHODS: A total of 29 children (24 males and 5 females) with breath holding spell in Second Xiangya Hospital, Central South University were enrolled for this study from October, 2009 to September, 2015. Their ages ranged from 3 months to 6 years, with an average of 1.82+/-1.27 years old. The control group consisted of 30 age-matched and gender-matched healthy children. All subjects were underwent electrocardiography by the SR-1000A comprehensive automatic electrocardiograph analyzer, and the changes of the ECG parameters were compared between the two groups.? RESULTS: Compared with the control group, the amplitude of P-wave of V5 lead was decreased [(44.10+/-23.98) vs (58.30+/-21.19) MUV, P<0.05], the amplitude of T-wave of V6 lead was increased [(423.80+/-122.6) vs (350.00+/-105.73) MUV, P<0.05], the amplitude of ST segment of II lead was increased [(84.80+/-39.97) vs (57.30+/-38.77) MUV, P<0.05], the amplitude of ST segment of aVR lead was increased [(-77.60+/-37.41) vs (-51.00+/-33.46) MUV, P<0.05], the amplitude of ST segment of aVL lead was increased [(35.20+/-28.24) vs (17.70+/-33.90) MUV, P<0.05], the amplitude of ST segment of V5 lead was increased [(111.00+/-59.36) vs (69.00+/-36.33) MUV, P<0.05], the amplitude of ST segment of V6 lead was increased [(79.30+/-45.51) vs (51.30+/-33.19) MUV, P<0.05]. ? CONCLUSION: The children with breath holding spell have autonomic nerve dysfunction. The amplitude of ST segment changes is sensitive. PMID- 27374445 TI - [Diagnostic value of human papillomavirus E6/E7 mRNA for residue and recurrence after cervical conization]. AB - OBJECTIVE: To explore the diagnostic value of human papillomavirus E6/E7 mRNA for residue and recurrence of cervical intraepithelial neoplasia (CIN) patients after cervical conization.? METHODS: A total of 154 patients, who underwent cervical conization and possessed complete follow-up data of high-grade cervical intraepithelial neoplasia (CINII, III), were subjected to thin-prep cytology test (TCT), HPV-DNA typing and HPV E6/E7 mRNA test in 3-6 months and 12 months after cervical conization. Abnormal cytology (>=ASC-US) or high-risk HPV-DNA (+) or HPV E6/E7 mRNA (+) cases were found by colposcopy and cervical biopsy pathological diagnosis.? RESULTS: Nine patients had residue and 22 recurred. HPV-DNA detections after cervical conization in 57 patients were positive. Among them, 30 patients had residual/recurrent lesions. HPV E6/E7 mRNA detections in 26 patients were positive. Among them, 24 patients had residual/recurrent lesions. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of diagnosis in the detection of HPV-DNA were 96.8%, 78%, 52.6%, 99%, and 81.8%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of diagnosis in the detection of HPV E6/E7 mRNA were 77.4%, 98.4%, 92.3%, 94.5%, and 94.2%, respectively. The specificity and positive predictive value of HPV E6/E7 mRNA test were greater than those of HPV-DNA typing test. There was a significant difference between the two groups (P<0.05).? CONCLUSION: Detection of HPV E6/E7 mRNA during the follow up period could timely and effectively forecast the risk of residue and recurrence of CIN after cervical conization, and reduce excessive examination and treatment. PMID- 27374446 TI - [Characteristics of health seeking behaviors for patients with psoriasis in a general hospital]. AB - OBJECTIVE: To explore the characteristics of health seeking behaviors and relevant factors among the outpatients with psoriasis in a general hospital, and to provide scientific evidence to modify the inappropriate health seeking behaviors for psoriasis patients and improve the therapeutic effect. ? METHODS: Using cross-sectional study design, a dermatological clinic in a general hospital was selected for this study. Two hundred psoriasis outpatients from 1st April to 30th September in 2014 were enrolled. A series of questionnaires were used to collect information regarding the social-demographic characteristics, health seeking behaviors, knowledge on psoriasis, and depressive and anxious symptoms.? RESULTS: Among 200 psoriasis outpatients, 141 patients (70.5%) experienced transfer treatment. One hundred and eighty-two patients (91.0%) went to formal hospitals in county for treatment when symptoms were firstly displayed; the other 18 patients (9.0%) went to village or community clinics, or the private clinics. Over 50% patients chose municipal hospital and 35.0% patients went to provincial hospital for medical treatment among the 182 patients. Ninety-one percent of the patients made decision for the first treatment after consulting with their spouses or relatives. According to the definition of the appropriate health seeking behavior in this study, 50 patients (25%) had inappropriate health seeking behaviors. Logistic regression analysis showed inappropriate health seeking behaviors correlated with the family whose income was less than 3 000 yuan per person per month (OR=2.232, 95%CI 1.086 to 4.585), patients who made the decision for the treatment with no discussion with other people when the symptoms appeared (OR=3.016, 95%CI 1.023 to 8.893), and the high score of the International Psoriasis Severity Index (OR=1.043, 95%CI 1.001 to 1.088). ? CONCLUSION: The dermatological practitioner should pay more attention to the factors, such as social-demographical characteristics, especially the low level of family income and their treatment experience. It is necessary for the general hospital to conduct health education for psoriasis outpatients to promote their appropriate health seeking behaviors. PMID- 27374447 TI - [Influential factors for anemia in pregnancy based on a nested case-control study in Changsha]. AB - OBJECTIVE: To explore the prevalence of anemia during pregnancy and the influential factors in changsha city, and to provide scientific evidence for prevention and intervention of anemia during pregnancy. ? METHODS: A cluster sampling of 713 mothers, who delivered baby between January 1, 2013 and December 31, 2013 in the three streets of kaifu district of Changsha, was selected to establish a retrospective cohort. The maternal health information during pregnancy was collected within 15 days after the delivery. The influential factors of anemia during pregnancy were analyzed by the method of retrospective nested case-control study and conditional logistic regression.? RESULTS: The prevalence of anemia during pregnancy in Changsha was 9.96%. The multiple conditional logistic regression results show that high family income (OR=0.632, P=0.020), high education level (OR=0.276, P=0.033), folic acid supplement (OR =0.248, P=0.050), iron supplement (OR=0.272, P<0.001) and eating blood products (OR=0.588, P=0.044) were the beneficial factors for anemia during pregnancy, while multipara (OR=2.917, P=0.003), long duration of menstrual period before pregnancy (OR=1.335, P=0.041), living in new decoration housing (OR=3.690, P=0.045) and tea-drinking (OR=1.365, P=0.094) were the risk factors for anemia during pregnancy. ? CONCLUSION: The prevalence of anemia during pregnancy in Changsha is below the average levels. The occurrence of anemia during pregnancy is closely related to the women's economic level and nutritional status. Women should strengthen maternal nutrition during pregnancy and bedroom environment monitor, drink little strong tea and improve the nutritional status of iron during pregnancy. PMID- 27374448 TI - [Status of subjective well-being for medical staff in a tertiary hospital]. AB - OBJECTIVE: To investigate the status of subjective well-being (SWB) for medical staffs who contact with patients directly in a tertiary hospital.? METHODS: Staffs from a tertiary hospital in Hunan province were investigated the SWB Scale (SWBS-cc20) from 2012 to 2014.? RESULTS: The scores of SWB for medical staffs are high (81.67+/-12.33). Among the 10 sub-dimensions of SWB, medical staffs performed the best in family atmosphere, personal growth, and interpersonal adaptation, while performed the worst in physical health, mental health and material contentment. Title, job nature, education and occupation significantly affected the status of SWB. Staffs who directly connected with patients have less scores of SWB than those who do not (t=-4.80, P<0.001). Moreover, they perform better in contentment (OR=0.079, 95% CI 1.278 to 2.214, P<0.001), but worse in mental health (OR=1.315, 95% CI 1.023 to 1.690, P<0.05) and physical health (OR=1.313, 95% CI 1.029 to 1.677, P<0.05).? CONCLUSION: Medical staffs have high scores of SWB. Staffs who directly connected with patients have less scores of SWB than those who do not. Moreover, they perform better in contentment, but worse in mental health and physical health. PMID- 27374449 TI - [Research progress in the regulation of endothelial nitric oxide synthase activity and cardiovascular diseases]. AB - Endothelial nitric oxide synthase (eNOS) is a major enzyme responsible for nitric oxide (NO) production. Both eNOS and NO play an important role in regulating vessel structure and function through participating in the physiological and pathological process. Generally, the phosphorylation of eNOS has been recognized as a common mechanism for regulation of eNOS function. However, recent studies have demonstrated several other new mechanisms, such as acetylation, S glutathionylation, and protein-protein interaction. This review highlights the basic structure and functions of eNOS as well as the relationship between regulation of eNOS activity and cardiovascular diseases. PMID- 27374450 TI - Image and pathological features of Ewing's sarcoma in the oral and maxillofacial region. AB - OBJECTIVE: To systematically evaluate the image and pathological features of Ewing's sarcoma (ES) in the oral and maxillofacial region.? METHODS: Eight patients with ES in the oral and maxillofacial region were enrolled for this study. The X-ray, computed tomography (CT), and magnetic resonance imaging (MRI) of ES and the pathological data were systematically evaluated.? RESULTS: X-ray image showed a diffuse radiolucency with cystic component and ill-defined borders for bone lesion. CT showed that there was osteolytic mass with extensive bone destruction and soft tissue infiltration, but no periosteal reactions were observed. MRI demonstrated that ES showed an inhomogeneous structure and blurred borders with invasion to adjacent soft tissue for bone lesion. Similar manifestation also showed in MRI images for patients with soft tissues. Histologically, ES composed of small round cells, and expressed CD99, neuron specific enolase (NSE) and vimentin (Vim) in all patients. Desmin (Des), CD34, epithelial membrane antigen (EMA), chromogranin A (ChgA), etc, were negatively expressed in ES cells.? CONCLUSION: X-ray, CT, and MRI are helpful to determine the property, extent and the relationship of ES with the surrounding tissues. Immunohistochemical stain of CD99, NSE, and Vim are helpful to confirm the pathological diagnosis of ES. PMID- 27374451 TI - [Clinical characteristics of histoplamosis in 8 patients: case report and literature review]. AB - To explore the clinical characteristics, imaging manifestation, diagnosis and treatment for histoplasmosis and to improve therapeutic level, we retrospectively analyzed the clinical data of 8 patients with biopsy-confirmed histoplasmosis from 2004 to 2014 in the Second Xiangya Hospital of Central South University and reviewed relevant literatures. The main clinical symptoms of histoplasmosis included fever, cough, expectoration, chest pain, blood-stained sputum, lymphadenectasis, etc. The major lung imaging features were mass, node or pneumonia-like performance. No case was diagnosed as histoplasimosis firstly. Four patients whose imaging manifestations were focal pulmonary lesion received lobectomy of lung lesions or wedge resection. Clinical and imaging manifestations in 3 patients, who treated with amphotericin B or its liposomal, itraconazole or fluconazole, were improved. The clinical symptoms and imaging findings of histoplasmosis are nonspecific. It is easy for the physicians to misdiagnose histoplasmosis as bacterial infection, lung cancer, tuberculosis lymphoma, etc. Therefore, it is significant and necessary to carry out multiple biopsies combined with multiple etiological examinations for patients with difficult diagnosis. PMID- 27374452 TI - [A case of Mullerian duct cyst torsion combined with bladder cancer]. AB - The diagnosis and treatment of a patient with Mullerian duct cyst torsion combined with bladder cancer were retrospectively analyzed. The patient received an open abdominal operation with right accessory resection plus pelvic adhesion release, and conducted microscopic examination for the bladder under general anesthesia. The results of histopathological examination confirmed the diagnosis of Mullerian duct cyst and papillary urothelial carcinoma at low level. After surgery, the patient received chemotherapy and follow-up observation, and all the indices for the patient were normal and no obvious discomfort. Although the final diagnosis of Mullerian duct cysts is based on histopathological examination, ultrasonography, CT scan and MRI can also detect it. Most of the Mullerian duct cysts are benign, and surgical excision is safe and effective. PMID- 27374453 TI - [A case of Legionella pneumonia with multiple organ failure]. AB - Legionella pneumonia (LP) is a rare systemic infectious disease, which is often misdiagnosed by clinicians due to the atypical symptoms. A middle-aged man who suffered from fever and dyspnea was diagnosed as community acquired pneumonia (CAP) in Changsha Central Hospital in March 2015. The treatment was unsatisfied firstly. The patients showed further symptoms of rhabdomyolysis, acute liver and renal failure, and impaired neural functions, who was diagnosed as LP with multiple organ failure based on a positive test for Legionella antibody. The patient was recovered after treated with moxifloxacin combined with azithromycin and continuous renal replacement therapy. LP should be paid attention when patient was diagnosed as CAP and failed to be treated. The satisfied outcome is achieved after application of macrolide, quinolones and comprehensive treatments. PMID- 27374454 TI - Patterns of Locoregional Relapses in Patients with Contemporarily Staged Stage III-N2 NSCLC Treated with Induction Chemotherapy and Resection: Implications for Postoperative Radiotherapy Target Volumes. AB - OBJECTIVES: Our aim was to evaluate locoregional relapse (LR) patterns after induction chemotherapy and surgery for stage III-N2 NSCLC staged with current standard methods and their impact on radiation target volumes for postoperative radiotherapy (PORT). METHODS: A total of 150 patients with stage III-N2 NSCLC from a prospective database of patients who underwent surgical resection at the University Hospitals of Leuven or the Oncologic Centre Limburg between 1998 and 2012 were included. Patients were staged with fluorodeoxyglucose F 18 positron emission tomography/computed tomography and brain imaging and treated with induction chemotherapy and surgery. PORT was performed for incomplete resection (R1/R2) and/or persistent nodal disease (ypN2). For the non-PORT group, we created a virtual planning target volume (PTV). In general, the clinical target volume encompassed the bronchial stump, the ipsilateral hilum, the subcarinal region (station 7), and the initially involved mediastinal lymph nodes. RESULTS: After a mean follow-up time of 49 months, the 5-year overall survival was 35.1% in all patients; disease-free survival was 31.8%. PORT was delivered to 70 patients. LR was seen in 26 patients in the PORT group (37%) and 32 in the non PORT group (40%). Fifty-eight nodal relapse sites were seen in the PORT group (2.2 sites per patient) versus 113 in the non-PORT group (3.5 sites per patient) (p < 0.01). In the PORT group, the most frequent sites of LR were the ipsilateral hilum (21%), lymph node station 7 (15%), ipsilateral station 4 (9%), ipsilateral station 5 (9%) and ipsilateral station 6 (9%). For the non-PORT group these were station 7 (19%), ipsilateral 4 (16%), and ipsilateral hilum (14%). The dominant pattern of failure was inside (inside or both inside and outside) the PTV. Regarding the out-of-PTV relapses, 47% and 69% of LRs occurred in the contralateral mediastinum for the PORT and non-PORT groups, respectively. Out-of PTV relapses occurred mostly in initially left-sided tumors. CONCLUSIONS: Despite the limitations of this retrospective study, our data support the role of PORT in decreasing local relapses. Because of the large number of out-of-PTV relapses in the contralateral mediastinum, inclusion of elective contralateral lymph node stations in the PTV could be considered in left-sided tumors. However, prospective randomized trials are needed to verify this. PMID- 27374455 TI - Silencing NKD2 by Promoter Region Hypermethylation Promotes Esophageal Cancer Progression by Activating Wnt Signaling. AB - INTRODUCTION: Naked cuticle homolog 2 (NKD2) was found to be frequently methylated in human breast and gastric cancers. However, the epigenetic changes and mechanisms of NKD2 in human esophageal cancer remain unclear. METHODS: Nine esophageal cancer cell lines and 154 cases of primary esophageal cancer samples were analyzed using methylation-specific polymerase chain reaction, immunohistochemical analysis, Western blot, and xenograft mouse models. RESULTS: Loss of NKD2 expression and complete methylation were found in KYSE150 and TE1 cells. Reduced NKD2 expression and partial methylation of the promoter region were observed in KYSE30, KYSE70, KYSE410, KYSE140, and COLO680 cells. High levels of NKD2 expression and unmethylation were detected in KYSE450 and TE8 cells. Reexpression of NKD2 was induced by 5-aza-2'-deoxycytidine in cells in which NKD2 was not expressed or cells in which NKD2 expression was reduced. NKD2 was methylated in 53.2% of human primary esophageal cancer samples (82 of 154), and promoter region hypermethylation was significantly associated with reduced expression of NKD2 (p < 0.01). NKD2 methylation was associated with tumor, node, and metastasis stage and lymph node metastasis (p < 0.01). Our results suggest that NKD2 is regulated by promoter region methylation and that methylation of NKD2 may serve as a prognostic marker in esophageal cancer. Our further studies demonstrate that NKD2 suppresses cell proliferation, colony formation, cell invasion, and migration and also induces G1/S checkpoint arrest in esophageal cancer cells. NKD2 suppressed xenograft tumor growth and inhibited Wnt signaling in human esophageal cancer cells. CONCLUSIONS: NKD2 is frequently methylated in human esophageal cancer, and the expression of NKD2 is regulated by promoter region methylation. NKD2 suppresses esophageal cancer progression by inhibiting Wnt signaling both in vitro and in vivo. PMID- 27374456 TI - The Clinical Impact of Solid and Micropapillary Patterns in Resected Lung Adenocarcinoma. AB - INTRODUCTION: Since the new adenocarcinoma (ADC) classification was presented in 2011, several authors have reported that patients with solid (S) and/or micropapillary (MP) predominant patterns showed a worse prognosis. On the other hand, there are several patients who have S and/or MP patterns even if their patterns are not predominant. However, the evaluation of these patients is uncertain. METHODS: A total of 531 ADCs were examined. We classified the patients into five subgroups according to the proportion of S and/or MP patterns: (1) both patterns absent (S-/MP-), (2) S predominant (S pre), (3) MP predominant (MP pre), (4) S pattern present although not predominant and MP pattern absent (S+ not pre/MP-), and (5) MP pattern present although not predominant (MP+ not pre). RESULTS: Of the 531 ADCs, 384 (72.3%) were classified as S-/MP-, 55 (10.4%) as S pre, 11 (2.1%) as MP pre, 42 (7.9%) as S+ not pre/MP-, and 39 (7.3%) as MP+ not pre. In a univariate analysis, the recurrence-free survival (RFS) and overall survival differed significantly among the five subgroups (p < 0.01 and p < 0.01, respectively). In a multivariate analysis, patients with S-/MP- had significantly higher RFS rates than did those with other subgroups. On the other hand, patients with MP pre had lower RFS rates than did those with other subgroups. CONCLUSION: Patients with S and/or MP patterns have a poorer prognosis even if their patterns are not predominant. The S and/or MP patterns must be treated at the time of diagnosis. PMID- 27374457 TI - Nanoparticle design considerations for molecular imaging of apoptosis: Diagnostic, prognostic, and therapeutic value. AB - The present review analyzes various approaches for the design and synthesis of different nanoparticles for imaging and therapy. Nanoparticles for computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and optical imaging are discussed. The influence of nanoparticle size, shape, surface charge, composition, surface functionalization, active targeting and other factors on imaging and therapeutic efficacy is analyzed. Cyto- and genotoxicity of nanoparticles are also discussed. Special attention in the review is paid to the imaging of apoptotic tissues and cells in different diseases. PMID- 27374458 TI - Poly(lactic acid) blends in biomedical applications. AB - Poly(lactic acid) (PLA) has become a "material of choice" in biomedical applications for its ability to fulfill complex needs that typically include properties such as biocompatibility, biodegradability, mechanical strength, and processability. Despite the advantages of pure PLA in a wider spectrum of applications, it is limited by its hydrophobicity, low impact toughness, and slow degradation rate. Blending PLA with other polymers offers a convenient option to enhance its properties or generate novel properties for target applications without the need to develop new materials. PLA blends with different natural and synthetic polymers have been developed by solvent and melt blending techniques and further processed based on end-use applications. A variety of PLA blends has been explored for biomedical applications such as drug delivery, implants, sutures, and tissue engineering. This review discusses the opportunities for PLA blends in the biomedical arena, including the overview of blending and postblend processing techniques and the applications of PLA blends currently in use and under development. PMID- 27374459 TI - The complex genetic landscape of acute myeloid leukaemia. PMID- 27374460 TI - mTOR inhibition in diffuse large B-cell lymphoma: new hope? PMID- 27374461 TI - Maintenance therapy in CLL: resolving the controversy. PMID- 27374462 TI - Improved survival with salvage autologous stem-cell transplantation in myeloma. PMID- 27374463 TI - The 52nd annual meeting of the American Society of Clinical Oncology. PMID- 27374464 TI - Everolimus combined with R-CHOP-21 for new, untreated, diffuse large B-cell lymphoma (NCCTG 1085 [Alliance]): safety and efficacy results of a phase 1 and feasibility trial. AB - BACKGROUND: The PI3K-mTORC pathway is upregulated in diffuse large B-cell lymphoma (DLBCL) and can be targeted with the mTOR complex 1 (mTORC1) inhibitor everolimus. Everolimus has activity in relapsed DLBCL. These data provide the rationale to combine everolimus with standard treatment for DLBCL of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone delivered in a 21 day cycle (R-CHOP-21) for six cycles. METHODS: We did a phase 1 and feasibility study (NCCTG 1085) of oral everolimus 10 mg/day plus R-CHOP-21 in patients aged at least 18 years with new, untreated, CD20-positive DLBCL (stages II-IV) in the NCCTG (Alliance) National Cancer Institute Cooperative Group (USA). Patients received standard R-CHOP-21 (intravenous rituximab 375 mg/m(2), intravenous cyclophosphamide 750 mg/m(2), intravenous doxorubicin 50 mg/m(2), and intravenous vincristine 1.4 mg/m(2) [maximum 2.0 mg] all on day 1 of the 21-day cycle; and oral prednisone 100 mg/m(2) each day on days 1-5 of the cycle) for six cycles with scheduled subcutaneous pegfilgrastim 6 mg on day 2 of each cycle. We tested two schedules: everolimus given in the fasting state either on days 1-10 or days 1-14 of the R-CHOP cycle. The primary endpoint of the phase 1 portion of this study was to establish the maximum tolerated dose of everolimus that could be combined with R-CHOP-21. The primary endpoint of the feasibility portion of the study was to determine the feasibility of the regimen, which was assessed by determining the rate of significant toxicity. Secondary endpoints were the proportion of patients who achieved an overall response, a complete response, event-free survival at 12 months and 24 months from enrolment, progression-free survival, and overall survival; relapse of DLBCL; and duration of response. We deemed patients as assessable for the primary endpoint in the phase 1 portion if they completed the first cycle as planned. In the feasibility portion, all patients who received at least one dose of everolimus were included. This trial is registered with ClinicalTrials.gov, number NCT01334502. FINDINGS: Between March 21, 2012, and Sept 15, 2014, we enrolled 26 patients into the study. Two were ineligible, therefore results are presented for 24 eligible patients. Nine patients were enrolled into the phase 1 portion of the trial (three given everolimus on days 1-10, and six given everolimus on days 1-14) without any dose limiting toxicities; therefore, everolimus 10 mg/day given on days 1-14 with R CHOP-21 was tested in 15 additional patients for a total of 24. One (5%, 95% CI 0 24%) of 21 patients had a toxicity during the feasibility phase-a treatment delay of 12 days due to grade 3 hypokalaemia possibly related to everolimus. The median follow-up was 21.5 months (IQR 17-29). 23 (96%, 95% CI 79-100%) of 24 patients achieved an overall response, and all 23 (96%, 79-100%) also attained a complete metabolic response by PET. The remaining patient withdrew consent after in cycle 1 and attained a complete response with R-CHOP alone. All 24 (100%) patients met 12-month event-free survival, and nine had sufficient follow-up data to be event free at 24 months. None of the 24 patients had died by the last follow-up (March 30, 2016), and none had had a relapse with DLBCL. Because no events occurred during the study or follow-up, we were unable to assess the duration of response or progression-free survival. The most common grade 3-4 adverse events were haematological; the most common of these was grade 4 neutropenia in 18 (75%) of 24 patients. Five (21%) of 24 had grade 3 febrile neutropenia. INTERPRETATION: The mTORC1 inhibitor everolimus given for 14 days in combination with R-CHOP-21 for patients with DLBCL is safe. These findings suggest that drugs that target the PI3K-mTORC pathway add benefit when combined with standard R-CHOP. The everolimus with R-CHOP regimen should be tested against standard R-CHOP alone in a randomised trial, to support the benefits of this novel combination noted in this study. FUNDING: National Cancer Institute of the US National Institutes of Health. PMID- 27374465 TI - Rituximab maintenance versus observation alone in patients with chronic lymphocytic leukaemia who respond to first-line or second-line rituximab containing chemoimmunotherapy: final results of the AGMT CLL-8a Mabtenance randomised trial. AB - BACKGROUND: In many patients with chronic lymphocytic leukaemia requiring treatment, induction therapy with rituximab plus chemotherapy improves outcomes compared with chemotherapy alone. In this study we aimed to investigate the potential of rituximab maintenance therapy to prolong disease control in patients who respond to rituximab-containing induction regimens. METHODS: In this randomised, international, multicentre, open-label, phase 3 clinical trial, we enrolled patients who had achieved a complete response (CR), CR with incomplete bone marrow recovery (CRi), or partial response (PR) to first-line or second-line rituximab-containing chemoimmunotherapy and randomly assigned them in a 1:1 ratio (central block randomisation in the electronic case report form system) to either intravenous rituximab 375 mg/m(2) every 3 months, or observation alone, for 2 years. Stratification was by country, line of treatment, type of chemotherapy added to the rituximab backbone, and degree of remission following induction. The primary endpoint was progression-free survival. Efficacy analysis was done in the intention-to-treat population. This is the final, event-triggered analysis. Final analysis was triggered by the occurrence of 92 events. This trial is registered with ClinicalTrials.gov, number NCT01118234. FINDINGS: Between April 1, 2010, and Dec 23, 2013, 134 patients were randomised to rituximab and 129 to observation alone. Median observation times were 33.4 months (IQR 25.7-42.8) for the rituximab group and 34.0 months (25.4-41.9) for the observation group. Progression-free survival was significantly longer in the rituximab maintenance group (47.0 months, IQR 28.5-incalculable) than with observation alone (35.5 months, 95% CI 25.7-46.3; hazard ratio [HR] 0.50, 95% CI 0.33-0.75, p=0.00077). The incidence of grade 3-4 haematological toxicities other than neutropenia was similar in the two treatment groups. Grade 3-4 neutropenia occurred in 28 (21%) patients in the rituximab group and 14 (11%) patients in the observation group. Apart from neutropenia, the most common grade 3-4 adverse events were upper (five vs one [1%] patient in the observation group) and lower (three [2%] vs one [1%]) respiratory tract infection, pneumonia (nine [7%] vs two [2%]), thrombopenia (four [3%] vs four [3%]), neoplasms (five [4%] vs four [3%]), and eye disorders (four [3%] vs two [2%]). The overall incidence of infections of all grades was higher among rituximab recipients (88 [66%] vs 65 [50%]). INTERPRETATION: Rituximab maintenance therapy prolongs progression-free survival in patients achieving at least a PR to induction with rituximab plus chemotherapy, and the treatment is well tolerated overall. Although it is associated with an increase in infections, there is no excess in infection mortality, suggesting that remission maintenance with rituximab is an effective and safe option in the management of chronic lymphocytic leukaemia in early treatment phases. FUNDING: Arbeitsgemeinschaft Medikamentose Tumortherapie gemeinnutzige GmbH (AGMT), Roche. PMID- 27374466 TI - Infusion of a non-HLA-matched ex-vivo expanded cord blood progenitor cell product after intensive acute myeloid leukaemia chemotherapy: a phase 1 trial. AB - BACKGROUND: The intensive chemotherapy regimens used to treat acute myeloid leukaemia routinely result in serious infections, largely due to prolonged neutropenia. We investigated the use of non-HLA-matched ex-vivo expanded cord blood progenitor cells to accelerate haemopoietic recovery and reduce infections after chemotherapy. METHODS: We enrolled patients with a diagnosis of acute myeloid leukaemia by WHO criteria and aged 18-70 years inclusive at our institution (Fred Hutchinson Cancer Research Center) into this phase 1 trial. The primary endpoint of the study was safety of infusion of non-HLA-matched expanded cord blood progenitor cells after administration of clofarabine, cytarabine, and granulocyte-colony stimulating factor priming. The protocol is closed to accrual and analysis was performed per protocol. The trial is registered with ClinicalTrials.gov, NCT01031368. FINDINGS: Between June 29, 2010, and June 26, 2012, 29 patients with acute myeloid leukaemia (19 newly diagnosed, ten relapsed or refractory) were enrolled. The most common adverse events were fever (27 [93%] of 29 patients) and infections (25 [86%] of 29 patients). We observed one case of acute infusional toxicity (attributed to an allergic reaction to dimethyl sulfoxide) in the 29 patients enrolled, who received 42 infusions of expanded progenitor cells. The following additional serious but expected adverse events were observed (each in one patient): grade 4 atrial fibrillation, grade 4 febrile neutropenia, lung infection with grade 4 absolute neutrophil count, colon infection with grade 4 absolute neutrophil count, grade 4 changed mental status, and one death from liver failure. No unexpected toxicity or graft-versus-host disease was observed. There was no evidence of in-vivo persistence of the expanded progenitor cell product in any patient beyond 14 days or induced alloimmunisation. INTERPRETATION: Infusion of the expanded progenitor cell product seemed safe and might provide a promising treatment method for patients with acute myeloid leukaemia. FUNDING: Biomedical Advanced Research and Development Authority in the US Department of Health and Human Services and Genzyme (Sanofi). PMID- 27374468 TI - Residual antibacterial activity of canine hair treated with topical antimicrobial sprays against Staphylococcus pseudintermedius in vitro. AB - BACKGROUND: Topical antimicrobial therapy is increasingly important in the treatment of canine pyoderma as the incidence of multidrug resistance has risen. However, little information is reported on the persistence of activity of topical antimicrobial products. OBJECTIVE: To determine the residual antibacterial activity of canine hairs treated with antimicrobial sprays. ANIMALS: Twelve privately owned dogs with no history of dermatological disease. METHODS: Dogs were treated once with four different spray products [(A) 1% chlorhexidine digluconate, (B) 2% miconazole nitrate, 2% chlorhexidine gluconate, tromethamine USP/disodium EDTA (TrizEDTA), (C) 3% chlorhexidine gluconate, phytosphingosine salicyloyl and (D) 4% chlorhexidine gluconate, TrizEDTA] in separate 5 * 5 cm sections on the trunk. Hairs were collected via shaving before, one hour after and 2, 4, 7 and 10 days after treatment. Hairs were incubated on agar plates streaked with Staphylococcus pseudintermedius for 24 h and the bacterial growth inhibition zone around the hairs was measured. RESULTS: There were significant overall treatment and day (P < 0.0001) differences in inhibition zones. The largest zones of inhibition were from hairs treated with spray B, followed by sprays D, C and A, respectively. All sprays demonstrated residual antimicrobial activity for the ten days evaluated. CONCLUSIONS AND CLINICAL SIGNIFICANCE: Results suggest that the efficacy of an antimicrobial spray is dependent on both the concentration and combination of active ingredients. Several ingredient profiles appear to effectively inhibit S. pseudintermedius growth for at least 10 days, which may be beneficial in the treatment of canine pyoderma. PMID- 27374467 TI - The effect of salvage autologous stem-cell transplantation on overall survival in patients with relapsed multiple myeloma (final results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open-label, phase 3 trial. AB - BACKGROUND: The Myeloma X trial previously reported improved durability of response (time to disease progression) in patients with relapsed multiple myeloma with salvage autologous stem-cell transplantation (ASCT) compared with oral cyclophosphamide in patients with multiple myeloma relapsing after a first ASCT. We report the final overall survival results of the trial. METHODS: BSBMT/UKMF Myeloma X was a multicentre, randomised, open-label, phase 3 trial done at 51 centres in the UK. Eligible patients with multiple myeloma relapsing after a previous ASCT were re-induced with intravenous bortezomib (1.3 mg/m(2) on days 1, 4, 8, 11), intravenous doxorubicin (9 mg/m(2) per day on days 1-4), and oral dexamethasone (40 mg/day on days 1-4, 8-11, and 15-18 during cycle 1 and days 1-4 during cycles 2-4), with supportive care as per local institutional protocols before randomisation in a 1:1 ratio to either high-dose melphalan (200 mg/m(2)) and salvage ASCT or weekly oral cyclophosphamide (400 mg/m(2) per week for 12 weeks). Randomisation was by permuted blocks stratified by length of first remission and response to re-induction treatment. The primary endpoint was time to disease progression; the study was also powered to detect a difference in the secondary endpoint, overall survival. Further secondary endpoints were the proportion of patients achieving an objective response, progression-free survival, overall survival, toxic effects and safety, pain, and quality of life. Prespecified exploratory endpoints included time to second objective disease progression (PFS2). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00747877, and the European Clinical Trials Database, number 2006-005890-24, and is now in long-term follow-up. FINDINGS: Between April 16, 2008, and Nov 19, 2012, 297 patients were registered into the study and 174 were randomly assigned to receive either high-dose melphalan and salvage ASCT (n=89) or oral weekly cyclophosphamide (n=85). 173 (58%) of 297 patients relapsed after more than 24 months from first ASCT. 75 (43%) of 174 randomised patients had died at follow-up: salvage ASCT (n=31 [35%]) versus oral weekly cyclophosphamide (n=44 [52%]). Updated time to disease progression shows continued advantage in the salvage ASCT group compared with the weekly cyclophosphamide group (19 months [95% CI 16-26] vs 11 months [9-12]; hazard ratio [HR] 0.45 [95% CI 0.31-0.64] log-rank p<0.0001). Median overall survival was superior in the salvage ASCT group compared with weekly cyclophosphamide group (67 months [95% CI 55-not estimable] vs 52 months [42-60]; log-rank p=0.022; HR 0.56 [0.35-0.90], p=0.0169). Time to second objective disease progression was superior in the salvage ASCT group compared with the weekly cyclophosphamide group (67 months [52-not estimable] vs 35 months [31-43]; HR 0.37 [0.24-0.57], log-rank p<0.0001). During extended follow-up, no further treatment-related or treatment-unrelated adverse events were reported. 15 second primary malignancies were reported in 12 patients (salvage ASCT [n=7] vs oral weekly cyclophosphamide [n=5]). The cumulative incidence of second primary malignancies at 60 months after trial entry was 5.2% (2.1-8.2). INTERPRETATION: Salvage ASCT increases overall survival during consolidation of re-induction treatment in patients with multiple myeloma at first relapse after a first ASCT. The delay of salvage ASCT to third-line treatment or later might not confer the same degree of advantage as seen with salvage ASCT at first relapse. FUNDING: Cancer Research UK, Janssen-Cilag, and Chugai Pharma UK. PMID- 27374469 TI - Evaluation of cytology collection techniques and prevalence of Malassezia yeast and bacteria in claw folds of normal and allergic dogs. AB - BACKGROUND: Canine bacterial and Malassezia paronychia are common secondary complications of atopic dermatitis and adverse food reactions. HYPOTHESIS/OBJECTIVES: The aim of this study was to compare three different sampling methods for claw fold cytology and to evaluate the numbers of bacteria, Malassezia yeast and inflammatory cells. ANIMALS: Sixty client-owned dogs were classified into three groups: (A) normal dogs; (B) allergic dogs with no clinical evidence of claw disease (brown staining, erythema, swelling, crusts or exudates); and (C) allergic dogs with clinical paronychia. METHODS: A prospective, blinded, split-plot study design was used. Claw folds from each dog were sampled using either a toothpick, tape preparation or direct impression smear. Slides were evaluated by two investigators for inflammatory cells, nuclear streaming, debris, corneocytes, yeast, intracellular (IC) cocci, extracellular (EC) cocci, IC rods and EC rods. For each parameter, data were compared between groups and between methods. Inter-reader agreements were calculated. RESULTS: Group C had significantly higher values of EC cocci and corneocytes than Groups A or B. Although Malassezia organisms were more prevalent in allergic dogs than normal dogs, the counts were not significantly different. There were significantly higher numbers of Malassezia organisms (P = 0.0016) and EC cocci (P = 0.0106) retrieved from samples collected with a toothpick compared to other methods. Tape preparations were associated with significantly more debris and corneocytes (both P < 0.0001) and impression smears with significantly more nuclear streaming (P = 0.0468). CONCLUSIONS AND CLINICAL IMPORTANCE: Sample collection using a toothpick optimizes the value of cytological results when sampling allergic dogs with clinical paronychia. PMID- 27374470 TI - A retrospective review of hyperaesthetic leucotrichia in horses in the USA. AB - BACKGROUND: Hyperaesthetic leucotrichia (HL) rarely affects horses and causes painful lesions on the dorsum that result in leucotrichia. This may be a variant of erythema multiforme (EM), but there are no studies investigating this condition. OBJECTIVES: Describe the clinical and histological features of HL and compare them to the histological features of EM. METHODS: A retrospective review of medical records from 1985 to 2015 identified 15 horses with HL. Thirteen biopsies of HL and five of EM were evaluated and compared. RESULTS: Arabian horses and their crosses (chi(2) (1) = 8.56, P < 0.01) and American paint horses (chi(2) (1) = 6.64, P < 0.05) were over represented. The onset of clinical signs was between April and September (14 of 15). The most common clinical signs were pain (15 of 15), leucotrichia (11 of 15), crusting (10 of 15) and alopecia (8 of 15) limited to darkly pigmented skin. The lesions recurred seasonally in 6 of 12 horses and unpredictably in 1 of 12 horse. The most common histological features were the presence of large stellate cells (13 of 13) and oedema (12 of 13) in the superficial dermis, perivascular to diffuse lymphocytic inflammation (13 of 13), pigmentary incontinence (12 of 13), apoptotic keratinocytes (9 of 13) and vesicle formation (8 of 13). Horses with EM (n = 5) had significantly more acanthosis (z = -2.40, P < 0.02) and lymphocytic exocytosis (z = -3.1, P < 0.004), satellitosis (Fisher's exact P = 0.02) and inflammation (z = -2.91, P < 0.004). Horses with HL had significantly more pigmentary incontinence (z = 2.13, P < 0.04) and superficial dermal oedema (z = 2.56, P < 0.002). CONCLUSIONS: HL affects primarily Arabian horses and American paint horses. It occurs mainly in summer and may recur. Histologically HL shares features with EM, but there are significant differences between them. PMID- 27374472 TI - Essential content of evidence-based clinical practice guidelines for bladder cancer: The Japanese Urological Association 2015 update. AB - The Japanese Urological Association revised the clinical practice guidelines for bladder cancer in April 2015. This was the first update carried out in the 6 years since the development of the initial clinical practice guidelines for bladder cancer in 2009. The descriptive content was revised, and additions were made with a focus on new-found evidence and advances in the latest medical practices, and on the basis of the increasingly aging population observed in the underlying social context in Japan. An algorithm for the treatment of bladder cancer has been presented as a new trial. In the present article, we will introduce the essential contents and clinical questions that address the present revisions. PMID- 27374473 TI - Characteristic distribution of finite-time Lyapunov exponents for chimera states. AB - Our fascination with chimera states stems partially from the somewhat paradoxical, yet fundamental trait of identical, and identically coupled, oscillators to split into spatially separated, coherently and incoherently oscillating groups. While the list of systems for which various types of chimeras have already been detected continues to grow, there is a corresponding increase in the number of mathematical analyses aimed at elucidating the fundamental reasons for this surprising behaviour. Based on the model systems, there are strong indications that chimera states may generally be ubiquitous in naturally occurring systems containing large numbers of coupled oscillators - certain biological systems and high-Tc superconducting materials, for example. In this work we suggest a new way of detecting and characterising chimera states. Specifically, it is shown that the probability densities of finite-time Lyapunov exponents, corresponding to chimera states, have a definite characteristic shape. Such distributions could be used as signatures of chimera states, particularly in systems for which the phases of all the oscillators cannot be measured directly. For such cases, we suggest that chimera states could perhaps be detected by reconstructing the characteristic distribution via standard embedding techniques, thus making it possible to detect chimera states in systems where they could otherwise exist unnoticed. PMID- 27374471 TI - C-Jun N-terminal kinase signalling pathway in response to cisplatin. AB - Cisplatin (cis diamminedichloroplatinum II, cDDP) is one of the most effective cancer chemotherapeutic agents and is used in the treatment of many types of human malignancies. However, inherent tumour resistance is a major barrier to effective cisplatin therapy. So far, the mechanism of cDDP resistance has not been well defined. In general, cisplatin is considered to be a cytotoxic drug, for damaging DNA and inhibiting DNA synthesis, resulting in apoptosis via the mitochondrial death pathway or plasma membrane disruption. cDDP-induced DNA damage triggers signalling pathways that will eventually decide between cell life and death. As a member of the mitogen-activated protein kinases family, c-Jun N terminal kinase (JNK) is a signalling pathway in response to extracellular stimuli, especially drug treatment, to modify the activity of numerous proteins locating in the mitochondria or the nucleus. Recent studies suggest that JNK signalling pathway plays a major role in deciding the fate of the cell and inducing resistance to cDDP-induced apoptosis in human tumours. c-Jun N-terminal kinase regulates several important cellular functions including cell proliferation, differentiation, survival and apoptosis while activating and inhibiting substrates for phosphorylation transcription factors (c-Jun, ATF2: Activating transcription factor 2, p53 and so on), which subsequently induce pro apoptosis and pro-survival factors expression. Therefore, it is suggested that JNK signal pathway is a double-edged sword in cDDP treatment, simultaneously being a significant pro-apoptosis factor but also being associated with increased resistance to cisplatin-based chemotherapy. This review focuses on current knowledge concerning the role of JNK in cell response to cDDP, as well as their role in cisplatin resistance. PMID- 27374474 TI - Robotic middle pancreatectomy with the double pursestring invaginated pancreaticogastrostomy (with video). PMID- 27374475 TI - Reply to letter to the editor "Petersen's Hernia after mini (one anastomosis) gastric bypass". PMID- 27374476 TI - Decompressive fasciotomy for acute compartment syndrome of the leg. PMID- 27374477 TI - Liver transplantation from donors after circulatory death following the withdrawal of life-sustaining therapies: An answer to the shortage of grafts? PMID- 27374478 TI - Outcome after fixation of metastatic proximal femoral fractures: A systematic review of 40 studies. AB - Endoprosthetic reconstruction, intramedullary nailing, and open reduction internal fixation (ORIF) are the most commonly practiced surgical strategies for treatment of metastatic proximal femoral fractures. This review describes functional outcome, local, and systemic complications. All three surgical strategies result in reasonable function on average; however, wide ranges indicate that both poor and good functional levels are obtained. We found that the overall reoperation rate was comparable for endoprosthesis and intramedullary nailing, but was higher for ORIF. J. Surg. Oncol. 2016;114:507-519. (c) 2016 Wiley Periodicals, Inc. PMID- 27374479 TI - Place dependent stimulation rates improve pitch perception in cochlear implantees with single-sided deafness. AB - In normal hearing, the pitch of an acoustic tone can theoretically be encoded by either the place of stimulation in the cochlea or the corresponding rate of vibration. Thus spectral attributes and temporal fine structure of an acoustic signal are naturally correlated. Cochlear implants (CIs), neural prosthetic devices that restore hearing in the profoundly hearing impaired, currently disregard this mechanism; electrical stimulation is provided at fixed electrode positions with default place independent stimulation rate assignments. This does not account for individual cochlear encoding depending on electrode array placement, variations in insertion depth, and the proximity to nerve fibers. Encoding pitch in such manner delivers limited tonal information. Consequently, music appraisal in CI users is often rated cacophonic while speech perception in quiet is close to normal in top performers. We hypothesize that this limitation in electric stimulation is at least partially due to the mismatch between frequency and place encoding in CIs. In the present study, we determined individual electrode locations by analysis of cochlear radiographic images obtained after surgery and calculated place dependent stimulation rates according to models of the normal tonotopic function. Pitch matching in CI users with single-sided deafness shows that place dependent stimulation rates allow thus far unparalleled restoration of tonotopic pitch perception. Collapsed data of matched pitch frequencies as a function of calculated electrical stimulation rate were well fitted by linear regression (R(2) = 0.878). Sound processing strategies incorporating place dependent stimulation rates are expected to improve pitch perception in CI users. PMID- 27374480 TI - Determinants of survival and attempted resection in patients with non-metastatic pancreatic cancer: An Australian population-based study. AB - BACKGROUND: There are indications that pancreatic cancer survival may differ according to sociodemographic factors, such as residential location. This may be due to differential access to curative resection. Understanding factors associated with the decision to offer a resection might enable strategies to increase the proportion of patients undergoing potentially curative surgery. METHODS: Data were extracted from medical records and cancer registries for patients diagnosed with pancreatic cancer between July 2009 and June 2011, living in one of two Australian states. Among patients clinically staged with non metastatic disease we examined factors associated with survival using Cox proportional hazards models. To investigate survival differences we examined determinants of: 1) attempted surgical resection overall; 2) whether patients with locally advanced disease were classified as having resectable disease; and 3) attempted resection among those considered resectable. RESULTS: Data were collected for 786 eligible patients. Disease was considered locally advanced for 561 (71%) patients, 510 (65%) were classified as having potentially resectable disease and 365 (72%) of these had an attempted resection. Along with age, comorbidities and tumour stage, increasing remoteness of residence was associated with poorer survival. Remoteness of residence and review by a hepatobiliary surgeon were factors influencing the decision to offer surgery. CONCLUSIONS: This study indicated disparity in survival dependent on patients' residential location and access to a specialist hepatobiliary surgeon. Accurate clinical staging is a critical element in assessing surgical resectability and it is therefore crucial that all patients have access to specialised clinical services. PMID- 27374481 TI - Chemical constituents from Melicope pteleifolia leaves. AB - Five acetophenones bearing spiroketal-hexofuranoside rings, one di-C-glycosidic acetophenone and two benzopyrans, along with 16 known compounds were isolated from the leaves of Melicope pteleifolia. Structures of all the isolates were elucidated using extensive spectroscopic methods, including 1D, 2D-NMR and HRESIMS. All the isolates were also evaluated for their neuraminidase inhibitory activities against H1N1, H9N2, wild-type H1N1 and oseltamivir-resistant H1N1 (H274Y mutation) virus strains. Of the isolates, tamarixetin 3-robinobioside was found to exhibit the strongest enzymatic inhibition (IC50 24.93 +/- 3.46, 23.19 +/- 5.41, 26.67 +/- 5.16 and 40.16 +/- 4.50 MUM, respectively). Selected candidates, kaempferol 3-robinobioside, kaempferol 3-O-beta-d-glucopyranosyl (1 > 2)-alpha-d-xylopyranoside and tamarixetin 3-robinobioside, also showed moderate reductions in H1N1-induced cytopathic effects on MDCK cells. PMID- 27374482 TI - Saponins of Agave: Chemistry and bioactivity. AB - The genus Agave comprises more than 400 species with geographical presence in the tropical and sub-tropical regions of the world. These plants have a rich history of folkloric use and are known for a wide spectrum of applications. Secondary metabolites of diverse chemical classes have been reported from Agave species. Owing to their pharmacological significance, the steroidal saponins of Agave have caught the attention of phytochemists, biologists and drug discovery scientists. The present review describes 141 steroidal saponins and sapogenins and covers the literature published from 1970 to 2015. It is a comprehensive and coherent presentation of the structures, methods of chemical profiling, structure elucidation and biological activities of the saponins and sapogenins reported from Agave. The article provides a perspective of the research on steroidal compounds of Agave. PMID- 27374483 TI - Quantifying passive muscle stiffness in children with and without cerebral palsy using ultrasound shear wave elastography. AB - AIM: The aim of this study was to compare passive muscle stiffness in children with cerebral palsy (CP) and children with typical development using a novel ultrasound technique: ultrasound shear wave elastography (SWE). METHOD: We conducted a prospective study of 13 children with CP (six females and seven males, median age 5y 1mo [interquartile range 4y 4mo-7y 8mo]) and 13 children with typical development (six females and seven males, median age 5y 3mo [interquartile range 4y 4mo-9y 4mo]). Demographic information and physical exam measurements were obtained in addition to shear modulus measurements (passive muscle stiffness) of the lateral gastrocnemius muscle at 20 degrees plantar flexion, 10 degrees plantar flexion, and 0 degrees plantar flexion using SWE. RESULTS: Children with CP had significantly greater shear modulus measurements at all three foot positions (p<0.050). When the shear modulus values were normalized to the baseline value for each child, there was no significant difference between the two groups. INTERPRETATION: Passive muscle stiffness, measured without the influence of spasticity, is greater in children with CP than in children with typical development when a muscle is at slack and at stretch. When shear modulus was normalized, the results indicate that muscle in children in both groups responds similarly to passive stretch. Further work includes evaluating effect of botulinum toxin on passive muscle properties. PMID- 27374484 TI - Plasmablastic transformation of plasma cell myeloma with heterotropic expression of CD3 and CD4: a case report. AB - Plasmablastic lymphoma (PBL) can rarely be seen as a transformation from plasma cell myeloma (PCM), especially in late stages of the disease where it portends a poorer prognosis and a different line of management for the patient. When unrelated to PCM, PBL is considered to be a separate aggressive variant of B-cell lymphoma typically seen in the oral cavity of immunocompromised adults. We describe a case of plasmablastic transformation having a pan T-cell phenotype with CD3 and CD4 positivity, in an immunocompetent elderly lady diagnosed with PCM. This 60-year-old lady presented with worsening backache and a 2-cm skin nodule in the left cervical region, while she was on treatment with vincristine, cyclophosphamide, dexamethasone (VCD), and bortezomib. On biopsy, the skin nodule showed an infiltrating lymphoid tumor composed of immunoblastic cells with brisk mitosis and apoptosis. On Immunohistochemistry (IHC), lymphoid cells revealed plasma cell markers CD38, CD138, CD56, and MUM1. Pan-T-cell markers CD3 and CD4 were also diffusely expressed in tumor cells. B-cell markers CD20 and PAX5 were not expressed; c-Myc IHC and EBER by in situ hybridization (ISH) were negative in the tumor. Mitotic index by Ki67 was >95%. Thus, a diagnosis of plasmablastic transformation in a known PCM case was made. This is the first case, to the best of our knowledge, with a heterotropic T-cell phenotype in a plasmablastic transformation from PCM. It is critical to correctly diagnose such cases as they may occasionally be misinterpreted as T-cell neoplasms. Clinically, a more aggressive treatment is indicated for such patients. Further studies in these cases may enhance our understanding of complex underpinnings of lymphoma biology. PMID- 27374486 TI - Isolation and characterization of Oya virus a member of Simbu serogroup, family Bunyaviridae, isolated from Karnataka, India. AB - During a study on Japanese encephalitis (JE) from Kolar district of Karnataka state, India in 1986; two virus isolates were obtained in infant Swiss albino mouse from a pig and a human serum sample. For characterization of these virus isolates, they were propagated in Vero CCL-81 cells. These virus isolates were screened for flaviviruses (Japanese encephalitis, West Nile, Dengue, Kyasanur forest disease) and Alphavirus (Chikungunya) by RT-PCR and found to be negative. Further these they were screened for bunyaviruses using genus-specific primers. A virus isolate from a human sample was sequenced using next generation sequencing; which identified it as Oya virus, Simbu group of the genus Orthobunyavirus of the family Bunyaviridae. Phylogenetic analysis of L, M, S (N and NSs) revealed its close association with Chinese strain of Oya virus in Simbu serogroup with the distance of 6.5>4.2>3.2% for nucleotides and 2.4>0.8>0.0% for the amino acid of L>M>S segments respectively. Based on the PCR results; an isolate from pig sample was also confirmed as Oya virus. This study was strengthened by findings of IgG antibody positivity against Oya virus in retrospective serum samples of suspected febrile illness cases from this area by an indigenously developed ELISA. Oya virus positivity was also recorded in human samples collected from Karnataka using nested RT-PCR. This is the first report of the presence of Oya virus in human samples. Further studies are needed to determine disease-causing potential in humans. PMID- 27374485 TI - Transcriptome Analysis on Monocytes from Patients with Neovascular Age-Related Macular Degeneration. AB - Mononuclear phagocytes (MPs), including monocytes/macrophages, play complex roles in age-related macular degeneration (AMD) pathogenesis. We reported altered gene expression signature in peripheral blood mononuclear cells from AMD patients, and a chemokine receptor signature on AMD monocytes. To obtain comprehensive understanding of MP involvement, particularly in peripheral circulation in AMD, we performed global gene expression analysis in monocytes. We separated monocytes from treatment-naive neovascular AMD (nvAMD) patients (n = 14) and age-matched controls (n = 15), and performed microarray and bioinformatics analysis. Quantitative real-time PCR was performed on other sets of nvAMD (n = 25), atrophic AMD (n = 21), and controls (n = 28) for validation. This validated microarray genes (like TMEM176A/B and FOSB) tested, including differences between nvAMD and atrophic AMD. We identified 2,165 differentially-expressed genes (P < 0.05), including 79 genes with log2 fold change >=1.5 between nvAMD and controls. Functional annotation using DAVID and TANGO demonstrated immune response alterations in AMD monocytes (FDR-P <0.05), validated by randomized data comparison (P < 0.0001). GSEA, ISMARA, and MEME analysis found immune enrichment and specific involved microRNAs. Enrichment of differentially-expressed genes in monocytes was found in retina via SAGE data-mining. These genes were enriched in non-classical vs. classical monocyte subsets (P < 0.05). Therefore, global gene expression analysis in AMD monocytes reveals an altered immune-related signature, further implicating systemic MP activation in AMD. PMID- 27374487 TI - Betulin attenuates atherosclerosis in apoE-/- mice by up-regulating ABCA1 and ABCG1. AB - AIM: Betulin is a pentacyclic triterpenoid isolated from the bark of yellow and white birch trees with anti-cancer and anti-malaria activities. In this study we examined the effects of betulin on atherosclerosis in apoE-/- mice and the underlying mechanisms. METHODS: Murine macrophage RAW264.7 cells and human monocyte-derived THP-1 cells were tested. Foam cell formation was detected with Oil Red O staining. Cholesterol efflux was assessed using [3H]-cholesterol efflux assay. The expression of ATP-binding cassette transporter A1 and G1 (ABCA1 and ABCG1) was examined using RT-PCR and Western-blotting. The ABCA1 promoter activity was evaluated using luciferase activity assay. Male apoE-/- mice fed on a high-fat-diet (HFD), and received betulin (20 and 40 mg.kg-1.d-1, ig) for 12 weeks. The macrophage content and ABCA1 expression in the aortic sinuses were evaluated with immunofluorescence staining. The hepatic, intestinal and fecal cholesterol were also analyzed in the mice. RESULTS: In RAW264.7 cells, betulin (0.1-2.5 MUg/mL) dose-dependently ameliorated oxLDL-induced cholesterol accumulation and enhanced cholesterol efflux. In both RAW264.7 and THP-1 cells, betulin increased the expression of ABCA1 and ABCG1 via suppressing the transcriptional repressors sterol-responsive element-binding proteins (SREBPs) that bound to E-box motifs in ABCA1 promoter, whereas E-box binding site mutation markedly attenuated betulin-induced ABCA1 promoter activity. In HFD-fed apoE-/- mice, betulin administration significantly reduced lesions in en face aortas and aortic sinuses. Furthermore, betulin administration significantly increased ABCA1 expression and suppressed macrophage positive areas in the aortic sinuses. Moreover, betulin administration improved plasma lipid profiles and enhanced fecal cholesterol excretion in the mice. CONCLUSION: Betulin attenuates atherosclerosis in apoE-/- mice by promoting cholesterol efflux in macrophages. PMID- 27374488 TI - Competitive antagonists facilitate the recovery from desensitization of alpha1beta2gamma2 GABAA receptors expressed in Xenopus oocytes. AB - AIM: The continuous presence of an agonist drives its receptor into a refractory state, termed desensitization. In this study, we tested the hypothesis that a competitive antagonist, SR95531, could facilitate the recovery of alpha1beta2gamma2 GABAA receptor from functional desensitization. METHODS: alpha1beta2gamma2 GABAA receptors were expressed in Xenopus oocytes. GABA-evoked currents were recorded using two-electrode voltage-clamp technique. Drugs were applied through perfusion. RESULTS: Long application of GABA (100 MUmol/L) evoked a large peak current followed by a small amplitude steady-state current (desensitization). Co-application of SR95531 during the desensitization caused a larger rebound of GABA current after removal of SR95531. Furthermore, application of SR95531 after removal of GABA increased the rate of receptor recovery from desensitization, and the recovery time constant was decreased from 59+/-3.2 s to 33+/-1.6 s. SR95531-facilitated receptor recovery from desensitization was dependent on the perfusion duration of SR95531. It was also dependent on the concentration of SR95531, and the curve fitting with Hill equation revealed two potency components, which were similar to the two potency components in inhibition of the steady-state current by SR95531. Bicuculline caused similar facilitation of desensitization recovery. CONCLUSION: SR95531 facilitates alpha1beta2gamma2 GABAA receptor recovery from desensitization, possibly through two mechanisms: binding to the desensitized receptor and converting it to the non desensitized state, and binding to the resting state receptor and preventing re desensitization. PMID- 27374489 TI - Dihydromyricetin protects neurons in an MPTP-induced model of Parkinson's disease by suppressing glycogen synthase kinase-3 beta activity. AB - AIM: It is general believed that mitochondrial dysfunction and oxidative stress play critical roles in the pathology of Parkinson's disease (PD). Dihydromyricetin (DHM), a natural flavonoid extracted from Ampelopsis grossedentata, has recently been found to elicit potent anti-oxidative effects. In the present study, we explored the role of DHM in protecting dopaminergic neurons. METHODS: Male C57BL/6 mice were intraperitoneally injected with 1 methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 d to induce PD. Additionally, mice were treated with either 5 or 10 mg/kg DHM for a total of 13 d (3 d before the start of MPTP, during MPTP administration (7 d) and 3 d after the end of MPTP). For the saline or DHM alone treatment groups, mice were injected with saline or DHM for 13 d. On d 14, behavioral tests (locomotor activity, the rotarod test and the pole test) were administered. After the behavioral tests, the mice were sacrificed, and brain tissue was collected for immunofluorescence staining and Western blotting. In addition, MES23.5 cells were treated with MPP+ and DHM, and evaluated using cell viability assays, reactive oxygen species (ROS) measurements, apoptosis analysis and Western blotting. RESULTS: DHM significantly attenuated MPTP-induced mouse behavioral impairments and dopaminergic neuron loss. In the MES23.5 cells, DHM attenuated MPP+-induced cell injury and ROS production in a dose-dependent manner. In addition, DHM increased glycogen synthase kinase-3 beta phosphorylation in a dose- and time-dependent manner, which may be associated with DHM-induced dopaminergic neuronal protection. CONCLUSION: The present study demonstrated that DHM is a potent neuroprotective agent for DA neurons by modulating the Akt/GSK-3beta pathway, which suggests that DHM may be a promising therapeutic candidate for PD. PMID- 27374490 TI - Discovery and structural optimization of 4-(4-(benzyloxy)phenyl)-3,4 dihydropyrimidin-2(1H)-ones as RORc inverse agonists. AB - AIM: Retinoic acid receptor-related orphan nuclear receptors (RORs) are orphan nuclear receptors that show constitutive activity in the absence of ligands. Among 3 subtypes of RORs, RORc is a promising therapeutic target for the treatment of Th17-mediated autoimmune diseases. Here, we report novel RORc inverse agonists discovered through structure-based drug design. METHODS: Based on the structure of compound 8, a previously described agonist of RORa, a series of 4-(4-(benzyloxy)phenyl)-3,4-dihydropyrimidin-2(1H)-one derivatives were designed and synthesized. The interaction between the compounds and RORc was detected at molecular level using AlphaScreen assay. The compounds were further examined in 293T cells transfected with RORc and luciferase reporter gene. Thermal stability shift assay was used to evaluate the effects of the compounds on protein stability. RESULTS: A total of 27 derivatives were designed and synthesized. Among them, the compound 22b was identified as the most potent RORc inverse agonist. Its IC50 values were 2.39 MUmol/L in AlphaScreen assay, and 0.82 MUmol/L in inhibition of the cell-based luciferase reporter activity. Furthermore, the compound 22b displayed a 120-fold selectivity for RORc over other nuclear receptors. Moreover, a molecular docking study showed that the structure-activity relationship was consistent with the binding mode of compound 22b in RORc. CONCLUSION: 4-(4-(Benzyloxy)phenyl)-3,4-dihydropyrimidin-2(1H)-one derivatives are promising candidates for the treatment of Th17-mediated autoimmune diseases, such as rheumatoid arthritis, psoriasis, and multiple sclerosis. PMID- 27374491 TI - Anticancer strategies based on the metabolic profile of tumor cells: therapeutic targeting of the Warburg effect. AB - Tumor cells rely mainly on glycolysis for energy production even in the presence of sufficient oxygen, a phenomenon termed the Warburg effect, which is the most outstanding characteristic of energy metabolism in cancer cells. This metabolic adaptation is believed to be critical for tumor cell growth and proliferation, and a number of onco-proteins and tumor suppressors, including the PI3K/Akt/mTOR signaling pathway, Myc, hypoxia-inducible factor and p53, are involved in the regulation of this metabolic adaptation. Moreover, glycolytic cancer cells are often invasive and impervious to therapeutic intervention. Thus, altered energy metabolism is now appreciated as a hallmark of cancer and a promising target for cancer treatment. A better understanding of the biology and the regulatory mechanisms of aerobic glycolysis has the potential to facilitate the development of glycolysis-based therapeutic interventions for cancer. In addition, glycolysis inhibition combined with DNA damaging drugs or chemotherapeutic agents may be effective anticancer strategies through weakening cell damage repair capacity and enhancing drug cytotoxicity. PMID- 27374493 TI - Hot Electrons at Solid-Liquid Interfaces: A Large Chemoelectric Effect during the Catalytic Decomposition of Hydrogen Peroxide. AB - The study of energy and charge transfer during chemical reactions on metals is of great importance for understanding the phenomena involved in heterogeneous catalysis. Despite extensive studies, very little is known about the nature of hot electrons generated at solid-liquid interfaces. Herein, we report remarkable results showing the detection of hot electrons as a chemicurrent generated at the solid-liquid interface during decomposition of hydrogen peroxide (H2 O2 ) catalyzed on Schottky nanodiodes. The chemicurrent reflects the activity of the catalytic reaction and the state of the catalyst in real time. We show that the chemicurrent yield can reach values up to 10(-1) electrons/O2 molecule, which is notably higher than that for solid-gas reactions on similar nanodiodes. PMID- 27374492 TI - Early spring sex differences in luteinizing hormone response to gonadotropin releasing hormone in co-occurring resident and migrant dark-eyed juncos (Junco hyemalis). AB - To optimally time reproduction, animals must coordinate changes in the hypothalamo-pituitary-gonadal (HPG) axis. The extent of intra-species variation in seasonal timing of reproductive function is considerable, both within and among populations. Dark-eyed junco (Junco hyemalis) populations are known to differ in their reproductive timing response to cues experienced in the same habitat in late winter/early spring. Specifically in juncos cohabitating on shared wintering grounds, residents initiate breeding and reproductive activity but migrants delay reproductive development and prepare to migrate before breeding. Here, we test the hypothesis that the pituitary gland acts as a 'control point' to modulate differential HPG axis activity across populations. We sampled free-living resident and migrant juncos on their shared over-wintering grounds in March, thus all individuals were experiencing the same environmental cues, including photoperiod. We predicted that during this critical time of transition, residents would more readily respond to repeated gonadotropin releasing hormone (GnRH) stimulation with increases in luteinizing hormone (LH), in contrast to migrants, which should delay full reproductive activity. Our data indicate that migrant females, while still on the overwintering grounds, have a reduced LH response to repeated GnRH injections compared to resident females. Male migrant and resident birds did not differ in their responsiveness to repeated GnRH. Our results suggest a sex difference in the costs of mistimed activation of the HPG axis, with female migrants being less responsive than residents females and males to repeated stimulation. Further, our data implicate a key role for the pituitary in regulating appropriate reproductive timing responses. PMID- 27374494 TI - If they are OK, we are OK: the experience of partners living with neuromyelitis optica. AB - AIM: Neuromyelitis optica (NMO) is a rare neuro-inflammatory condition characterized by acute relapses causing severe visual or physical disability. The impact on family members and their experiences have not been studied. The study aims were to explore the lived experience of partners of people with NMO and to investigate potential carer burden in this population. METHOD: A mixed-method design was used; 11 partners of people with NMO completed semi-structured interviews; 54 partners completed Zarit Burden Interview and Hospital Anxiety and Depression Scale. RESULTS: Three qualitative themes influenced partners' quality of life (QoL): role/relationship; it's all about them; and the impact of NMO. Life changed dramatically for participants after the first NMO attack, necessitating responsibility for physical, financial, social, and emotional support. As NMO symptoms improved and stabilized, freedom and QoL for spouses also improved, albeit with on-going worries regarding the impact of potential devastating future relapses. Quantitative findings showed mild/moderate carer burden (46%), mild/moderate anxiety (59%), and mild/moderate depression (24%). No partner indicated severe carer burden, anxiety, or depression. CONCLUSION: Participants regarded themselves as partners rather than carers whom require assessment and support for their emotional and health well-being. Health-care professionals need to acknowledge the important role partners play in the dynamics of the family unit, through greater discussion and inclusion. Implications for Rehabilitation NMO has a strong impact on couples, resulting in both physical caregiving needs and anxiety regarding the unpredictability of potential devastating relapses. Partners do not necessarily experience clinically significant "burden", anxiety or depression, and tools which screen for this may not capture the nature of their experiences. Health-care professionals need to acknowledge, consult, and respect the experience of partners during assessment and implementation of action plans. Partners should be individually assessed based upon the physical and emotional dependency created by NMO to improve their health and well-being. PMID- 27374495 TI - Unusually high genetic diversity in the Bornean Limnonectes kuhlii-like fanged frogs (Anura: Dicroglossidae). AB - A fanged frog Limnonectes kuhlii was once thought to be wide-ranging in Southeast Asia, but is now confined to its type locality Java through recent phylogenetic studies, which clarified heterospecific status of non-Javanese populations, and monophyly of Bornean populations. However, large genetic differences among Bornean populations suggest occurrence of cryptic species, which we test using dense geographic sampling. We estimated the phylogenetic relationships among samples of Bornean populations together with their putative relatives from the continental Southeast Asia, using 2517bp sequences of the 12S rRNA, tRNA(val), and 16S rRNA of mitochondrial DNA, and 2367bp sequences of the NCX1, POMC, and RAG1 of nuclear genes. In the mtDNA trees, Bornean L. kuhlii-like frogs formed a monophyletic group split into 18 species lineages including L. hikidai, with the deepest phylogenetic split separating L. cintalubang from the remaining species. Almost all of these lineages co-occur geographically, and two to three lineages were found syntopically in each locality. Co-occurrence of more than one lineage may be maintained by differential morphology and microhabitat selection. These syntopic lineages should be regarded as distinct species. Our results clearly indicate that taxonomic revision is urgent to clarify many evolutionary problems of Bornean L. kuhlii-like frogs. PMID- 27374496 TI - Spin Funneling for Enhanced Spin Injection into Ferromagnets. AB - It is well-established that high spin-orbit coupling (SOC) materials convert a charge current density into a spin current density which can be used to switch a magnet efficiently and there is increasing interest in identifying materials with large spin Hall angle for lower switching current. Using experimentally benchmarked models, we show that composite structures can be designed using existing spin Hall materials such that the effective spin Hall angle is larger by an order of magnitude. The basic idea is to funnel spins from a large area of spin Hall material into a small area of ferromagnet using a normal metal with large spin diffusion length and low resistivity like Cu or Al. We show that this approach is increasingly effective as magnets get smaller. We avoid unwanted charge current shunting by the low resistive NM layer utilizing the newly discovered phenomenon of pure spin conduction in ferromagnetic insulators via magnon diffusion. We provide a spin circuit model for magnon diffusion in FMI that is benchmarked against recent experiments and theory. PMID- 27374497 TI - In memoriam: Dr. Andrew E. Czeizel (April 03, 1935-August 10, 2015). PMID- 27374498 TI - Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation. AB - Remodeling of the tricarboxylic acid (TCA) cycle is a metabolic adaptation accompanying inflammatory macrophage activation. During this process, endogenous metabolites can adopt regulatory roles that govern specific aspects of inflammatory response, as recently shown for succinate, which regulates the pro inflammatory IL-1beta-HIF-1alpha axis. Itaconate is one of the most highly induced metabolites in activated macrophages, yet its functional significance remains unknown. Here, we show that itaconate modulates macrophage metabolism and effector functions by inhibiting succinate dehydrogenase-mediated oxidation of succinate. Through this action, itaconate exerts anti-inflammatory effects when administered in vitro and in vivo during macrophage activation and ischemia reperfusion injury. Using newly generated Irg1(-/-) mice, which lack the ability to produce itaconate, we show that endogenous itaconate regulates succinate levels and function, mitochondrial respiration, and inflammatory cytokine production during macrophage activation. These studies highlight itaconate as a major physiological regulator of the global metabolic rewiring and effector functions of inflammatory macrophages. PMID- 27374499 TI - Influence of different combinations of wall materials on the microencapsulation of jussara pulp (Euterpe edulis) by spray drying. AB - The objective of this work was to study the spray drying of jussara pulp using ternary mixtures of gum Arabic (GA) and modified starch (MS) together with either whey protein concentrate (WPC) or soy protein isolate (SPI), as the carrier agents. Two experimental mixture designs and triangular response surfaces were used to evaluate the effects of the mixtures on the responses for powders formulated with GA:MS:WPC and GA:MS:SPI, respectively. The spray drying process was selected for each carrier agent mixture, aiming to maximum the process yield (PY), solubility (S), retention of total anthocyanins (RTA) and encapsulation efficiency (EE). It was shown that the ternary formulations showed higher PY, S and RTA than the pure and binary formulations, as well as good results for EE and a low moisture content, showing that the use of GA and MS together with either WPC or SPI provide better microencapsulation of the jussara pulp. PMID- 27374500 TI - Determination and stability of divicine and isouramil produced by enzymatic hydrolysis of vicine and convicine of faba bean. AB - The aglycones of vicine and convicine, divicine and isouramil, are the causative agents of favism and, therefore, should be analysed along with vicine and convicine in research seeking to eliminate them. This study investigated the stability of the aglycones produced by hydrolysis with beta-glucosidase. Reversed phase, high-performance liquid chromatography (HPLC) with UV detection was shown to be able to observe both aglycone formation and further reactions in isolated fractions and extract made from faba bean and in faba bean suspension. Divicine and isouramil were unstable and degraded almost completely in extract in 60min and completely in fractions in 120min at a pH of 5 at 37 degrees C. Adding sodium ascorbate delayed degradation of divicine. Divicine was more stable at 20 degrees C than at 37 degrees C. Being able to show formation and degradation of the aglycones, the proposed method allows monitoring of the vicine and convicine detoxification process. PMID- 27374501 TI - The application of headspace gas chromatography coupled to tandem quadrupole mass spectrometry for the analysis of furan in baby food samples. AB - Selective methodology employing a tandem quadrupole mass spectrometer coupled to a gas chromatograph with headspace autosampler (HS-GC-MS/MS) was elaborated in this study. Application of the elaborated procedure resulted in a limit of detection of 0.021MUgkg(-1) and a limit of quantification of 0.071MUgkg(-1). The mean recoveries during in-house validation ranged from 89% to 109%, and coefficients of variation for repeatability ranged from 4% to 11%. The proposed analytical method was applied for monitoring the furan content of 30 commercial baby food samples available on the Latvian retail market. The level of furan found in these samples varied from 0.45 to 81.9MUgkg(-1), indicating that infants whose sole diet comprises baby food sold in jars and cans are exposed constantly to furan. Samples containing vegetables and meat had higher levels of furan than those containing only fruits. PMID- 27374502 TI - Microchannel emulsification study on formulation and stability characterization of monodisperse oil-in-water emulsions encapsulating quercetin. AB - The study used microchannel emulsification (MCE) to encapsulate quercetin in food grade oil-in-water (O/W) emulsions. A silicon microchannel plate (Model WMS 1-2) comprised of 10,300 discrete 10*104MUm microslots was connected to a circular microhole with an inner diameter of 10MUm. 1% (w/w) Tween 20 was used as optimized emulsifier in Milli-Q water, while 0.4mgml(-1) quercetin in different oils served as a dispersed phase. The MCE was carried by injecting the dispersed phase at 2mlh(-1). Successful emulsification was conducted below the critical dispersed phase flux, with a Sauter mean diameter of 29MUm and relative span factor below 0.25. The O/W emulsions remained stable in terms of droplet coalescence at 4 and 25 degrees C for 30days. The encapsulation efficiency of quercetin in the O/W emulsions was 80% at 4 degrees C and 70% at 25 degrees C during the evaluated storage period. PMID- 27374503 TI - Interfacial properties of Quillaja saponins and its use for micellisation of lutein esters. AB - Natural food colourants, colouring foods and bioactive food ingredients need to be solubilised for their incorporation in food. Aim of the present study was to investigate the micelle-forming properties of saponins from Quillaja saponaria Mollina (QS) in order to solubilise a lutein ester extract for its incorporation in food matrices. QS showed a high surface activity and functionality with respect to micellisation as derived from interfacial tension measurements and subsequent data fitting to the classical Frumkin model. The composition of the aqueous phase affected the lutein ester incorporation as revealed by particle size, zeta potential and colour measurements. In terms of morphology of lutein ester loaded saponin micelles (LMS), cryo-TEM micrographs showed depending on the composition of the medium both, spherical and elongated branched micelles. PMID- 27374504 TI - Towards green analysis of virgin olive oil phenolic compounds: Extraction by a natural deep eutectic solvent and direct spectrophotometric detection. AB - The determination of phenolic compounds in extra virgin olive oils (EVOO) by means of rapid, low-cost, environment-free methods would be a desirable achievement. A natural deep eutectic solvent (DES) based on glucose and lactic acid was considered as extraction solvent for phenolic compounds in EVOO. DESs are green solvents characterized by high availability, biodegradability, safety, and low cost. The spectrophotometric characteristics of DES extracts of 65 EVOO samples were related to the total phenolic content of the oils, assessed by methanol-water extraction coupled to the Folin-Ciocalteu assay. A regression model (ncalibration=45, nvalidation=20), including the absorbance at two wavelengths (257, 324nm), was obtained, with an adjusted R(2)=0.762. Therefore the DES could provide a promising and viable approach for a green screening method of phenolic compounds in EVOO, by means of simple spectrophotometric measurements of extracts, even for on-field analysis (for example in olive mills). PMID- 27374505 TI - Discriminative study of a potato (Solanum tuberosum L.) cultivation region by measuring the stable isotope ratios of bio-elements. AB - Compared to other foods, the use of common bio-elements to identify the geographical origin of potato remains limited. Thus, this study aimed to verify whether the cultivation regions of raw potato tubers could be determined by the stable isotope composition analysis of bio-elements. delta(13)CVPDB and delta(15)NAIR in potato were influenced by region and cultivar, whereas delta(18)OVSMOW and delta(34)SVCDT were only influenced by region (p<0.0001). A two-dimensional plot of delta(18)OVSMOW and delta(34)SVCDT effectively distinguished between high and low altitude regions, and also reliably discriminated Wanju, Haenam, and Boseong cultivars in low altitude regions. delta(34)SVCDT was the main component that was responsible for the separation of samples in the principal component analysis (eigenvector of -0.6209) and orthogonal projection to latent structure-discriminant analysis (VIP value of 1.0566). In conclusion, this study improves our understanding of how the isotope composition of potato tubers varies with respect to cultivation regions and cultivars. PMID- 27374506 TI - Wild almond (Prunus scoparia L.) as potential oilseed resource for the future: Studies on the variability of its oil content and composition. AB - Wild almond genetic resources have still not received considerable attention for oil chemical compositions and uses. The aim of this study was to assess the levels of variation in oil content and fatty acid composition in forty Iranian accessions of Prunus scoparia L. (Spach) to identify genotypes with desirable traits in terms of oil quantity, quality and industrial utilization. Oil parameters and indices were measured, and fatty acid methyl ester analysis was carried out by gas liquid chromatography. Oleic and linoleic fatty acids showed high variability among accessions, ranging from 232.4 to 359.6g/kg oil and from 190.7 to 348.8g/kg oil, respectively. Total unsaturated fatty acid fraction was higher than total saturated fatty acid. The ranges of saponification number (199.2-202.1), iodine value (104.8-125.7kg I2/kg) and cetane number (43.8-48.8), confirmed that the oils have industrial potentialities. Results could contribute to select wild almond genotypes as genetic sources for oil production. PMID- 27374507 TI - Electromembrane extraction and spectrophotometric determination of As(V) in water samples. AB - In this study, for the first time electromembrane extraction (EME) was used as a highly efficient sample pre-treatment method for the UV-VIS spectrophotometric determination of As(V) in water samples. The influences of experimental parameters during EME were investigated and optimized using one-variable-at-a time methodology as follows: organic solvent: 1-octanol+2.5% (V/V) di-(2 ethylhexyl) phosphate, applied voltage: 70V, extraction time: 15min, pH of acceptor: 13, stirring rate: 750rpm. The method allowed the determination of As(V) in the range of 5-300ngmL(-1). The relative standard deviation was found to be within the range of 3.4-7.6%. The limit of detection, corresponding to a signal to noise ratio of three, was 1.5ngmL(-1). The proposed method was finally applied to the determination of As(V) in water samples and relative recoveries ranging from 95 to 102% were obtained. PMID- 27374508 TI - A detection method of vegetable oils in edible blended oil based on three dimensional fluorescence spectroscopy technique. AB - Edible blended vegetable oils are made from two or more refined oils. Blended oils can provide a wider range of essential fatty acids than single vegetable oils, which helps support good nutrition. Nutritional components in blended oils are related to the type and content of vegetable oils used, and a new, more accurate, method is proposed to identify and quantify the vegetable oils present using cluster analysis and a Quasi-Monte Carlo integral. Three-dimensional fluorescence spectra were obtained at 250-400nm (excitation) and 260-750nm (emission). Mixtures of sunflower, soybean and peanut oils were used as typical examples to validate the effectiveness of the method. PMID- 27374509 TI - Effect of proteolysis on the sialic acid content and bifidogenic activity of ovomucin hydrolysates. AB - Ovomucin, accounting for ~3.5% of egg white proteins, contains 2.6-7.4% of sialic acid; sialic acid is suggested to play important roles in host-recognition, cognition and memory development. However, ovomucin's limited water solubility might restrict its future applications. The objective of the study was to examine the effect of proteolysis of ovomucin on the sialic acid content and bifidogenic activity of ovomucin hydrolysates. Ovomucin extract was hydrolyzed by 14 proteases with yields and DHs ranging from 42.6% (flavourzyme) to 97.4% (protease N), and 2.4% (flavourzyme) to 46.3% (pronase), respectively. Ovomucin hydrolyzed by pronase and protex 26L showed molecular weight (Mw) distributions less than 40kDa while others larger than 200kDa. Allergenicity of ovomucin hydrolysates was significantly reduced (P<0.05) in comparison to ovomucin extract. The content of sialic acid in hydrolysates ranged from 0.1% (protex 26L) to 3.7% (pronase). Ovomucin hydrolysates did not generally support growth of Bifidobacterium spp. in vitro. PMID- 27374510 TI - Effects of pretreatments on anthocyanin composition, phenolics contents and antioxidant capacities during fermentation of hawthorn (Crataegus pinnatifida) drink. AB - The effect of microwave and heat pretreatment on the content and composition of anthocyanins, phenolics, and the antioxidant capacity of hawthorn drink were studied. Nine anthocyanins were isolated by chromatographic separation from the Zirou hawthorn source and their structure identified using HPLC-DAD-ESI/MS analysis. Heat and microwave pretreatments had a significant impact on the relative contents of hawthorn anthocyanins, such as cyanidin-3-galactoside (82.9% and 76.9%, respectively) and cyanidin-3-glucoside (9.2% and 11.5%, respectively). Pretreatment had no significant effect on pH, total soluble solid or total acid. More anthocyanins remained after heat treatment than after microwaving (0.745mg/100mL), and were 52.4% higher than the control group after storage for 7days. The colour density of the heat treated group was higher than the control group (24.5%) after 12days of fermentation. The main antioxidant capacities of the hawthorn drinks came from total polyphenolics rather than total anthocyanins or total flavonoids. PMID- 27374511 TI - QuEChERS-based purification method coupled to ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to determine six quaternary ammonium compounds (QACs) in dairy products. AB - QuEChERS-based purification coupled with UPLC-MS/MS method, was developed for six quaternary ammonium compounds (QACs) determination in dairy products. Powder samples were firstly dispersed by water. Protein in liquid milk was precipitated and sample solution was extracted by acetonitrile. QuEChERS-based purification was used to purify the solution. QACs were finally separated by HILIC column and detected in MRM mode of MS/MS under ESI(+). The stable isotope benzyl-2,3,4,5,6 d5-dimethyltetradecylammonium bromide (C14-BAC-d5) was used as an internal standard. This method was validated in terms of linearity, sensitivity, precision, accuracy. Linear relations were favorable for QACs over the selected concentration ranges of 0.2-50MUg/L, with correlation coefficients greater than 0.999. The limits of detection (LODs) were in the range of 0.4-14.5MUg/kg. Recoveries were between 91.2% and 115% with RSDs of 2.8-7.5% for intra-day precision and 3.7-6.7% for inter-day precision. This validated method was successfully applied to determine the QACs concentrations in dairy products. PMID- 27374512 TI - Relationship between 4-hydroxy-2-hexenal contents and commercial grade by organoleptic judgement in Japanese dried laver Porphyra spp. AB - To evaluate the correlation between the commercial grade determined by organoleptic judgment panel and chemical substances in dried laver Porphyra spp., we analyzed the contents of free amino acids, 5'-nucleotides, total lipids, fatty acids, alpha-tocopherol, lipophilic pigments, and aldehydes in several grades of laver that had been classified by an organoleptic judgment panel. Compared with the lower-grade laver samples, the excellent-grade laver samples contained higher concentrations of free amino acids, 5'-nucleotides, total lipids, alpha tocopherol, chlorophyll a, and beta-carotene and lower concentrations of aldehydes such as 4-hydroxy-2-hexenal (HHE), propanal, butanal, and 1-hexanal, which are formed during lipid peroxidation of n-3 or n-6 polyunsaturated fatty acids. In addition, the HHE content was strongly correlated with the propanal content in the analyzed laver (r(2)=0.9123). These results showed that the commercial grade assigned by an organoleptic judgment panel was correlated with chemical substances associated with color, taste, and the prevention of lipid oxidation. PMID- 27374513 TI - Geographical classification of Italian saffron (Crocus sativus L.) based on chemical constituents determined by high-performance liquid-chromatography and by using linear discriminant analysis. AB - One hundred and forty-four Italian saffron samples produced in the years from 2009 to 2015 in five distinct areas located in four different regions, Abruzzo (L'Aquila), Tuscany (Florence), Umbria (Cascia and Citta della Pieve) and Sardinia, have been analysed by high-performance liquid chromatography with diode array detection. Intensities of the chromatographic peaks attributed to crocins, safranal, picrocrocin and its derivatives and flavonoids were considered as variables in linear discriminant analysis to attempt geographical classification. The results revealed that spices produced at different sites of the Italian territory can be discriminated with good accuracy. The differentiation of saffron cultivated in Sardinia from those produced in Central Italy was mainly attributed to different contents of the most abundant crocins. Good differentiation of spices produced in close sites of Central Italy was also observed, 88% of validation samples being correctly classified; some minor crocins are responsible for such discrimination. PMID- 27374514 TI - Method for determination of fatty acids in bovine colostrum using GC-FID. AB - Bovine colostrum is potentially valuable source of essential fatty acids (FAs), but so far only few studies have made the effort to estimate FA composition of this potential resource. The aim of current research was to fill this gap with selecting and validating an accurate procedure for the analysis of the composition of the FAs in bovine colostrum. We used colostrum samples of Holstein Friesian cattle from Marja experimental farm as a test material. The validated method includes derivatization, in which FAs are sent through esterification with the acidic catalyst boron trifluoride. Formed methyl esters of fatty acids (FAMEs) were analysed using GC-FID. The obtained LOD and the LOQ of FAMEs were 0.11-0.68 and 0.37-2.27ppm, respectively. The analysis of fortified samples showed very good and similar recoveries, indicating that the method proposed here can be routinely used for determination and investigation of the fatty acids in dairy products. PMID- 27374515 TI - Discrimination of Citrus reticulata Blanco and Citrus reticulata 'Chachi' by gas chromatograph-mass spectrometry based metabolomics approach. AB - Citri Reticulatae Pericarpium, mainly including the pericarp of Citrus reticulata Blanco and the pericarp of Citrus reticulata 'Chachi', has been consumed daily as food and dietary supplement for centuries. In this study, GC-MS based metabolomics was employed to compare comprehensively the volatile constituents in Citrus reticulata Blanco and Citrus reticulata 'Chachi'. Principal component analysis and orthogonal partial least squares discrimination analysis indicated that samples could be distinguished effectively from one another. Fifteen metabolites were finally identified for use as chemical markers in discrimination of Citri Reticulatae Pericarpium samples. The antimicrobial activity against Gram negative and Gram-positive bacteria of the volatile oil from Citrus reticulata Blanco and Citrus reticulata 'Chachi' was investigated preliminarily. PMID- 27374516 TI - Effect of chemical stress on germination of cv Dalia bean (Phaseolus vularis L.) as an alternative to increase antioxidant and nutraceutical compounds in sprouts. AB - The aim of this study was to determine the effect of chitosan (CH), salicylic acid (SA) and hydrogen peroxide (H2O2) at different concentrations on the antinutritional and nutraceutical content, as well as the antioxidant capacity of bean sprouts (cv Dalia). All elicitors at medium and high concentrations reduced the antinutritional content of lectins (48%), trypsin inhibitor (57%), amylase inhibitor (49%) and phytic acid (56%). Sprouts treated with CH, SA and H2O2 (7MUM; 1 and 2mM, and 30mM respectively) increased the content of phenolic compounds (1.8-fold), total flavonoids (3-fold), saponins (1.8-fold) and antioxidant capacity (37%). Furthermore, the UPLC-ESI-MS/MS analysis showed an increase of several nutraceutical compounds in bean sprouts treated with SA such as coumaric (8.5-fold), salicylic (115-fold), gallic (25-fold) and caffeic (1.7 fold) acids, as well as epigallocatechin (63-fold), rutin (41-fold) and quercetin (16.6-fold) flavonoids. The application of elicitors in bean seed during sprouting enhances their nutraceutical properties. PMID- 27374517 TI - Physical and antimicrobial properties of thyme oil emulsions stabilized by ovalbumin and gum arabic. AB - Natural biopolymer stabilized oil-in-water emulsions were formulated using ovalbumin (OVA), gum arabic (GA) solutions and their complexes. The influence of interfacial structure of emulsion (OVA-GA bilayer and OVA/GA complexes emulsions) on the physical properties and antimicrobial activity of thyme oil (TO) emulsion against Escherichia coli (E. coli) was evaluated. The results revealed that the two types of emulsions with different oil phase compositions remained stable during a long storage period. The oil phase composition had an appreciable influence on the mean particle diameter and retention of the TO emulsions. The stable emulsion showed a higher minimum inhibitory concentration (MIC), and the TO emulsions showed an improved long-term antimicrobial activity compared to the pure thyme oil, especially complexes emulsion at pH 4.0. These results provided useful information for developing protection and delivery systems for essential oil using biopolymer. PMID- 27374518 TI - Response surface methodology for evaluation and optimization of process parameter and antioxidant capacity of rice flour modified by enzymatic extrusion. AB - For the purpose of investigating the effect of enzyme concentration (EC), barrel temperature (BT), moisture content (MC), and screw speed (SS) on processing parameters (product temperature, die pressure and special mechanical energy (SME)) and product responses (extent of gelatinization (GE), retention rate of total phenolic content (TPC-RR)), rice flour extruded with thermostable alpha amylase was analyzed by response surface methodology. Stepwise regression models were computed to generate response surface and contour plots, revealing that both TPC-RR and GE increased as increasing MC while expressed different sensitivities to BT during enzymatic extrusion. Phenolics preservation was benefited from low SME. According to multiple-factor optimization, the conditions required to obtain the target SME (10kJ/kg), GE (100%) and TPC-RR (85%) were: EC=1.370/00, BT=93.01 degrees C, MC=44.30%, and SS=171.66rpm, with the actual values (9.49kJ/kg, 99.96% and 87.10%, respectively) showing a good fit to the predicted values. PMID- 27374519 TI - Development, validation and application of a hydrophilic interaction liquid chromatography-evaporative light scattering detection based method for process control of hydrolysis of xylans obtained from different agricultural wastes. AB - Purified standards of xylooligosaccharides (XOSs) (DP2-6) were first prepared from a mixture of XOSs using solid phase extraction (SPE), followed by semi preparative liquid chromatography both under hydrophilic interaction liquid chromatography (HILIC) modes. Then, an accurate quantitative analysis method based on hydrophilic interaction liquid chromatography-evaporative light scattering detection (HILIC-ELSD) was developed and validated for simultaneous determination of xylose (X1), xylobiose (X2), xylotriose (X3), xylotetraose (X4), xylopentaose (X5), and xylohexaose (X6). This developed HILIC-ELSD method was applied to the comparison of different hydrolysis methods for xylans and assessment of XOSs contents from different agricultural wastes. The result indicated that enzymatic hydrolysis was preferable with fewer by-products and high XOSs yield. The XOSs yield (48.40%) from sugarcane bagasse xylan was the highest, showing conversions of 11.21g X2, 12.75g X3, 4.54g X4, 13.31g X5, and 6.78g X6 from 100g xylan. PMID- 27374521 TI - Striking changes in volatile profiles at sub-zero temperatures during over ripening of 'Beibinghong' grapes in Northeastern China. AB - The evolution of free and glycosidically bound volatile compounds in 'Beibinghong' (Vitis vinifera*Vitis amurensis) grape berries throughout on-vine over-ripening and freezing processes was studied in two vintages. The aroma profiles of 'Beibinghong' icewine berries were characterized by C6 compounds, higher alcohols and terpenoids in free fractions and carbonyl compounds, higher alcohols, C6 alcohols and terpenoids in bound fractions. With regard to free volatile compounds, there was a decrease in the concentration of C6 compounds, terpenols and norisoprenoids and an increase of terpene oxides during over ripening process. A striking alteration of volatile profile occurred at sub-zero temperatures, particularly for the free fractions such as C6 alcohols, higher alcohols and oxidative terpene derivatives. These changes were attributed to a series of reactions (biotransformation, oxidation and anaerobic metabolism) induced by water loss and especially freeze-thaw cycles. PCA revealed temperature and rainfall affected the accumulation of volatile compounds during over-ripening processes. PMID- 27374520 TI - Characterization of virgin olive oils produced with autochthonous Galician varieties. AB - The interest of Galician oil producers (NW Spain) in recovering the ancient autochthonous olive varieties Brava and Mansa has increased substantially in recent years. Virgin olive oils produced by co-crushing both varieties in two different proportions, reflecting the usual and most common practice adopted in this region, have gradually emerged for the production of virgin olive oils. Herein, the sensory and chemical characteristics of such oils were characterized by quality and genuineness-related parameters. The results of chemical analysis are discussed in terms of their effective contribution to the sensory profile, which suggests useful recommendations for olive oil producers to improve the quality of oils. Antioxidant compounds, together with aromas and coloured pigments were determined, and their contribution in determining the functional value and the sensory properties of oils was investigated. In general, given the high levels of phenolic compounds (ranging between 254 and 375mg/kg oil), tocopherols (about 165mg/kg oil) and carotenoids (10-12mg/kg oil); these are oils with long stability, especially under dark storage conditions, because stability is reinforced with the contribution of chlorophylls (15-22mg/kg oil). A major content of phenolic compounds, as well as a predominance of trans-2-hexen-1-al within odor-active compounds (from 897 to 1645MUg/kg oil), responsible for bitter sensory notes. This characterization allows to developing new antioxidant-rich and flavour-rich VOOs, when co-crushing with a higher proportion of Brava olives, satisfying the consumers' demand in having access to more healthy dishes and peculiar sensory attributes. PMID- 27374522 TI - Determination of whey adulteration in milk powder by using laser induced breakdown spectroscopy. AB - A rapid and in situ method has been developed to detect and quantify adulterated milk powder through adding whey powder by using laser induced breakdown spectroscopy (LIBS). The methodology is based on elemental composition differences between milk and whey products. Milk powder, sweet and acid whey powders were produced as standard samples, and milk powder was adulterated with whey powders. Based on LIBS spectra of standard samples and commercial products, species was identified using principle component analysis (PCA) method, and discrimination rate of milk and whey powders was found as 80.5%. Calibration curves were obtained with partial least squares regression (PLS). Correlation coefficient (R(2)) and limit of detection (LOD) values were 0.981 and 1.55% for adulteration with sweet whey powder, and 0.985 and 0.55% for adulteration with acid whey powder, respectively. The results were found to be consistent with the data from inductively coupled plasma - mass spectrometer (ICP-MS) method. PMID- 27374523 TI - Bioaccessibility and degradation of naturally occurring arsenic species from food in the human gastrointestinal tract. AB - Humans are exposed to organic arsenic species through their diet and therefore, are susceptible to arsenic toxicity. Investigating the transformations occurring in the gastrointestinal tract will influence which arsenic species to focus on when studying metabolism in cells. Using a physiologically based extraction test, the bioaccessibility of arsenic species was determined after the simulated gastrointestinal digestion of rice, seaweed and fish. Pure standards of the major arsenic species present in these foodstuffs (arsenic glutathione complexes, arsenosugars and short chain fatty acids) were also evaluated to assess the effect of the food matrix on bioaccessibility and transformation. Approximately 80% of arsenic is released from these foodstuffs, potentially becoming available. Hydrolysis and demethylation of arsenic glutathione complexes and arsenosugars standards was observed, but no transformations occurred to arsenosugars present in seaweed. Demethylation of MA and DMA from rice occurs increasing the amount of inorganic arsenic species available for metabolism. PMID- 27374524 TI - Application of elevated temperature-dispersive liquid-liquid microextraction for determination of organophosphorus pesticides residues in aqueous samples followed by gas chromatography-flame ionization detection. AB - In the present study, an elevated temperature, dispersive, liquid-liquid microextraction/gas chromatography-flame ionization detection was investigated for the determination, pre-concentration, and extraction of six organophosphorus pesticides (malathion, phosalone, dichlorvos, diazinon, profenofos, and chlorpyrifos) residues in fruit juice and aqueous samples. A mixture of 1,2 dibromoethane (extraction solvent) and dimethyl sulfoxide (disperser solvent) was injected rapidly into the sample solution heated at an elevated temperature. Analytical parameters, including enrichment factors (1600-2075), linearity (r>0.994), limits of detection (0.82-2.72ngmL(-1)) and quantification (2.60 7.36ngmL(-1)), relative standard deviations (<7%) and extraction recoveries (64 83%), showed the high efficiency of the method developed for analysis of the target analytes. The proposed procedure was used effectively to analyse selected analytes in river water and fruit juice, and diazinon was found at ngmL(-1) concentrations in apple juice. PMID- 27374526 TI - Tuning the pH-shift protein-isolation method for maximum hemoglobin-removal from blood rich fish muscle. AB - A main challenge preventing optimal use of protein isolated from unconventional raw materials (e.g., small pelagic fish and fish by-products) using the pH-shift method is the difficulty to remove enough heme-pigments. Here, the distribution of hemoglobin (Hb) in the different fractions formed during pH-shift processing was studied using Hb-fortified cod mince. Process modifications, additives and prewashing were then investigated to further facilitate Hb-removal. The alkaline pH-shift process version could remove considerably more Hb (77%) compared to the acidic version (37%) when proteins were precipitated at pH 5.5; most Hb was removed during dewatering. Protein precipitation at pH 6.5 improved total Hb removal up to 91% and 74% during alkaline and acid processing, respectively. Adding phytic acid to the first supernatant of the alkaline process version yielded 93% Hb removal. Combining one prewash with phytic acid at pH 5.5 followed by alkaline/acid pH-shift processing increased Hb removal up to 96/92%. PMID- 27374525 TI - Immobilization of Candida antarctica lipase B onto SBA-15 and their application in glycerolysis for diacylglycerols synthesis. AB - In this study, Candida antarctica lipase B (CALB) was immobilized on SBA-15 with three pore diameters. CALB loading was found increased with CALB concentration increasing from 20.3 to 80.12MUg/ml. Higher CALB loading was observed from SBA-15 with pore diameters at 8.1nm (SBA-15(8.1)), yet highest hydrolytic activity was found at SBA-15(12.5). Thermal stability of the immobilized CALB (SBA-15-CALB) samples was greatly influenced by their water content, after 4h storage at 70 degrees C, 8.93 and 67.4% of the initial activity was observed from SBA-15-CALB samples with water content at 9.23 and 3.22% respectively. The SBA-15-CALB samples were then used in glycerolysis of corn oil, and 53.6wt% of diacylglycerols was obtained after optimization. The operational stability was tested, and after 5 consecutive applications, 92.5 and 80.3% of the initial glycerolysis activity was remained respectively from SBA-15(6.6)-CALB and SBA 15(12.5)-CALB. PMID- 27374527 TI - Evaluation of nutritional and antioxidant properties of the tropical fruits banana, litchi, mango, papaya, passion fruit and pineapple cultivated in Reunion French Island. AB - Much attention is paid to the beneficial action of fruits against obesity-related oxidative stress. This study evaluated nutritional and antioxidant properties of banana, litchi, mango, papaya, passion fruit and pineapple from Reunion French Island. Results showed that total amounts of carbohydrates, vitamin C and carotenoids were 7.7-67.3g glucose equivalent, 4.7-84.9mg ascorbic acid equivalent and 26.6-3829.2MUg beta-carotene equivalent/100g fresh weight, respectively. Polyphenols were detected as the most abundant antioxidants (33.0 286.6mg gallic acid equivalent/100g fresh weight) with the highest content from passion fruit. UPLC-MS analysis led to identify epigallocatechin and quercetin derivatives from banana and litchi, ferulic, sinapic, syringic and gallic acids from pineapple and mango, and piceatannol from passion fruit. Polyphenol-rich extracts protected red blood cells and preadipose cells against oxidative stress. Altogether, these findings highlight nutritional benefits of French tropical fruits and their possible interest to improve antioxidant capacities of the body during obesity. PMID- 27374528 TI - Non-enzymatic browning reaction of glucosamine at mild conditions: Relationship between colour formation, radical scavenging activity and alpha-dicarbonyl compounds production. AB - Glucosamine (GlcN, 5% w/v) was incubated in either phosphate buffer or ammonium hydroxide solutions at 40 and 60 degrees C for up to 48h in order to yield caramel solutions. Non-enzymatic browning was monitored via changes in absorption at 280, 320 and 420nm and the physico-chemical properties as well as the generation of short chain alpha-dicarbonyl compounds were evaluated. Accumulation of GlcN autocondensation products (280nm) proceeded in parallel with the development of pre-melanoidins (320nm) and melanoidins (420nm). The reactive alpha-dicarbonyls were detected at temperature as low as 40 degrees C within 3h with a maximum level of diacetyl recorded at 6h. The caramel solutions showed a high efficacy in scavenging DPPH and ABTS radicals in accordance with the increasing browning intensity. The results suggest that GlcN browning can be modulated according to the specific desired properties to produce a multi functional food ingredient that has health-promoting effects. PMID- 27374529 TI - Acrylamide formation in vegetable oils and animal fats during heat treatment. AB - The method of liquid chromatographic tandem mass spectrometry was utilized and modified to confirm and quantify acrylamide in heating cooking oil and animal fat. Heating asparagine with various cooking oils and animal fat at 180 degrees C produced varying amounts of acrylamide. The acrylamide in the different cooking oils and animal fat using a constant amount of asparagine was measured. Cooking oils were also examined for peroxide, anisidine and iodine values (or oxidation values). A direct correlation was observed between oxidation values and acrylamide formation in different cooking oils. Significantly less acrylamide was produced in saturated animal fat than in unsaturated cooking oil, with 366ng/g in lard and 211ng/g in ghee versus 2447ng/g in soy oil, followed by palm olein with 1442ng/g. PMID- 27374531 TI - The textural properties and microstructure of konjac glucomannan - tungsten gels induced by DC electric fields. AB - Konjac glucomannan - tungsten (KGM-T) gels were successfully prepared under DC electric fields, in the presence of sodium tungstate. The textural properties and microstructure of the gels were investigated by Texture Analyzer, Rheometer and SEM. Based on the response surface methodology (RSM) results, the optimum conditions for KGM-T gel springiness is 0.32% sodium tungstate concentration, 0.54% KGM concentration, 24.66V voltage and 12.37min treatment time. Under these conditions, the maximum springiness value of KGM-T gel is 1.21mm. Steady flow measurement indicated that KGM-T gel showed characteristic non-Newtonian pseudoplastic behaviour, with low flow behaviour indexes in the shear thinning region. SEM demonstrated the porosity of the freeze-dried samples. These findings may pave the way to use DC electric fields for the design and development of KGM gels and to apply KGM gels for practical applications. PMID- 27374530 TI - (Poly)phenolic fingerprint and chemometric analysis of white (Morus alba L.) and black (Morus nigra L.) mulberry leaves by using a non-targeted UHPLC-MS approach. AB - This study reports the (poly)phenolic fingerprinting and chemometric discrimination of leaves of eight mulberry clones from Morus alba and Morus nigra cultivated in Spain. UHPLC-MS(n) (Ultra High Performance Liquid Chromatography Mass Spectrometry) high-throughput analysis allowed the tentative identification of a total of 31 compounds. The phenolic profile of mulberry leaf was characterized by the presence of a high number of flavonol derivatives, mainly glycosylated forms of quercetin and kaempferol. Caffeoylquinic acids, simple phenolic acids, and some organic acids were also detected. Seven compounds were identified for the first time in mulberry leaves. The chemometric analysis (cluster analysis and principal component analysis) of the chromatographic data allowed the characterization of the different mulberry clones and served to explain the great intraspecific variability in mulberry secondary metabolism. This screening of the complete phenolic profile of mulberry leaves can assist the increasing interest for purposes related to quality control, germplasm screening, and bioactivity evaluation. PMID- 27374532 TI - Microencapsulation of canola oil by lentil protein isolate-based wall materials. AB - The overall goal was to encapsulate canola oil using a mixture of lentil protein isolate and maltodextrin with/without lecithin and/or sodium alginate by spray drying. Initially, emulsion and microcapsule properties as a function of oil (20% 30%), protein (2%-8%) and maltodextrin concentration (9.5%-18%) were characterized by emulsion stability, droplet size, viscosity, surface oil and entrapment efficiency. Microcapsules with 20% oil, 2% protein and 18% maltodextrin were shown to have the highest entrapment efficiency, and selected for further re-design using different preparation conditions and wall ingredients (lentil protein isolate, maltodextrin, lecithin and/or sodium alginate). The combination of the lentil protein, maltodextrin and sodium alginate represented the best wall material to produce microcapsules with the highest entrapment efficiency (~88%). The lentil protein-maltodextrin-alginate microcapsules showed better oxidative stability and had a stronger wall structure than the lentil protein-maltodextrin microcapsules. PMID- 27374533 TI - A new kinetic model of ultrasound-assisted extraction of polysaccharides from Chinese chive. AB - Chinese chive, a famous green vegetable, is widely cultivated in the Asia. In the present study, we found that ultrasound caused the degradation of Chinese chive polysaccharides (CCP) in the process of extraction. Since lacking the consideration of polysaccharide degradation, the traditional kinetic models can not reflect the real extraction process of CCP. Therefore, a modified kinetic model was thus established by introducing a parameter of degradation coefficient based on the Fick's second law, suggesting the diffusion and degradation of CCP is highly dependent on the ultrasonic power, extraction temperature and solid liquid ratio. According to this modified model, the maximum CCP yield was obtained under an optimal extraction condition including extraction temperature 37 degrees C, ultrasonic power 458 w, extraction time 30min and solid-liquid ratio 1:32. The objective polysaccharides responding to ultrasound were shown to be four different fractions, contributing to the increased diffusion and degradation of CCP by ultrasound treatment. PMID- 27374534 TI - Spent coffee grounds, an innovative source of colonic fermentable compounds, inhibit inflammatory mediators in vitro. AB - Spent coffee grounds (SCG), rich in dietary fiber can be fermented by colon microbiota producing short-chain fatty acids (SCFAs) with the ability to prevent inflammation. We investigated SCG anti-inflammatory effects by evaluating its composition, phenolic compounds, and fermentability by the human gut flora, SCFAs production, nitric oxide and cytokine expression of the human gut fermented unabsorbed-SCG (hgf-NDSCG) fraction in LPS-stimulated RAW 264.7 macrophages. SCG had higher total fiber content compared with coffee beans. Roasting level/intensity reduced total phenolic contents of SCG that influenced its colonic fermentation. Medium roasted hgf-NDSCG produced elevated SCFAs (61:22:17, acetate, propionate and butyrate) after prolonged (24h) fermentation, suppressed NO production (55%) in macrophages primarily by modulating IL-10, CCL-17, CXCL9, IL-1beta, and IL-5 cytokines. SCG exerts anti-inflammatory activity, mediated by SCFAs production from its dietary fiber, by reducing the release of inflammatory mediators, providing the basis for SCG use in the control/regulation of inflammatory disorders. The results support the use of SGC in the food industry as dietary fiber source with health benefits. PMID- 27374535 TI - Selection of grapevine leaf varieties for culinary process based on phytochemical composition and antioxidant properties. AB - Grapevine leaves are an abundant sub-product of vineyards which is devalued in many regions. The objective of this work is to study the antioxidant activity and phytochemical composition of ten grapevine leaf varieties (four red varieties: Tinta Amarela, Tinta Roriz, Touriga Franca, and Touriga Nacional; and six white varieties: Codega do Larinho, Fernao Pires, Gouveio, Malvasia Fina, Rabigato, and Viosinho) to select varieties to be used as food ingredients. White grapevine leaves revealed higher antioxidant potential. Malvasia Fina reported better antioxidant properties contrasting with Touriga Franca. Phenolic content varied between 112 and 150mgGAEg(-1) of extract (gallic acid equivalents), hydroxycinnamic acid derivatives and flavonols varied between 76 and 108mgCAEg( 1) of extract (caffeic acid equivalents) and 39 and 54mgQEg(-1) of extract (quercetin equivalents). Malvasia Fina is a good candidate for culinary treatment due to its antioxidant properties and composition in bioactive compounds. PMID- 27374536 TI - Authentication of Italian PDO lard using NIR spectroscopy, volatile profile and fatty acid composition combined with chemometrics. AB - This study analysed the usefulness of near infrared spectroscopy (NIRS), combined with volatile compound (VOC) and fatty acid (FA) analyses, for the authentication of the unique Italian Valle d'Aosta Arnad Protected Designation of Origin (PDO) lard. Ensuring the authenticity of high value meat products remains an emerging topic within the food sector. This study validated a FA, VOC and NIRS model for use in the authentication of Arnad PDO lard. The model showed a high potential rate to recognize patterns in lard samples. In particular the sensitivity and specificity calibration values were both 100%, and cross-validation models were performed using FAs and VOCs separately. The NIRS model obtained sensitivity and specificity values of 98.2% in the calibration data set, and 94.4% in the cross validation step. This analytical approach may represent an effective tool to prevent food fraud, which is crucial for meat derived products with a high commercial value. PMID- 27374537 TI - Structural and physicochemical characterization of Sphenostylis stenocarpa (Hochst. ex A. Rich.) Harms tuber starch. AB - Several characteristics of African Yam Bean tuber starch (AYB) were studied and compared with that of a well-known native potato starch (P). The diameter of AYB granules ranged from 5.7MU to 49MU with a median at 19.5MU. During its pasting, AYB exhibited a low peak of viscosity in accordance with its low granules swelling and disintegration capacity. The gelatinization temperature of AYB was 75.2 degrees C while that of P was 60.4 degrees C. AYB was observed to be more stable during thermo-gravimetrical Analysis. Its degradation peak was observed at 308 degrees C while that of P was 303 degrees C. The X-ray diffraction analysis revealed that AYB belongs to the A-type crystalline group instead of C-type as claimed for several legumes starches. The stability of AYB and its capacity to structure starch-water systems make this resource an interesting ingredient for new food and non-food products. PMID- 27374538 TI - Effect of 4-hydroxy-2-nonenal treatment on the IgE binding capacity and structure of shrimp (Metapenaeus ensis) tropomyosin. AB - Lipid peroxidation can react with free amines of proteins and induce modification of structural and functional properties. This study presents the IgE binding capacity and structural changes of shrimp tropomyosin (TM) under oxidative stress with 4-hydroxy-2-nonenal (HNE). IgE binding capacity was evaluated with the dot blot assay and inhibition enzyme-linked immunosorbent assay. A decrease in IgE binding capacity of TM was found with 0.01mM HNE treatment, which was more significant when the HNE concentration was increased to 0.5mM. The conformational changes of TM, as characterized by fluorescence spectroscopy, circular dichroism spectroscopy and ultraviolet absorption spectroscopy, correlated well with IgE binding capacity changes. Further LC-ESI-MS/MS analyses showed that the side chain groups of alanine, leucine, lysine and histidine had been modified by HNE. These results suggested that the HNE-induced conformational changes of TM significantly influenced its allergenicity and that these changes were caused by the modification of specific amino acids residues. PMID- 27374539 TI - Stability of polyphenols in chokeberry juice treated with gas phase plasma. AB - Chokeberry juice was subjected to cold atmospheric gas phase plasma and changes in hydroxycinnamic acids, flavonols and anthocyanins were monitored. Plasma treatments were carried out under different treatment times and juice volumes under constant gas flow (0.75dm(3)min(-1)). The results were compared against control (untreated) and pasteurized chokeberry juice (80 degrees C/2min). During pasteurization, the most unstable were hydroxycinnamic acids with losses of up to 59%, while flavonols and anthocyanins increased by 5% and 9%, respectively. On the contrary, plasma treated chokeberry juice showed higher concentrations of hydroxycinnamic acids and 23% loss of anthocyanins in comparison to untreated juice. In order to obtain the optimal cold plasma treatment parameters principal component and sensitivity analysis were used. Such parameters can be potentially used for pasteurization in terms of phenolic stability of chokeberry juice. Optimal treatment was at 4.1min and sample volume of 3cm(3). PMID- 27374540 TI - Effect of xanthan/enzyme-modified guar gum mixtures on the stability of whey protein isolate stabilized fish oil-in-water emulsions. AB - The effect of xanthan gum (XG) and enzyme-modified guar (EMG) gum mixtures on the physicochemical properties and oxidative stability of 2wt% whey protein isolate (WPI) stabilized oil-in-water (O/W) emulsions containing 20%v/v fish oil was investigated. EMG was obtained by hydrolyzing native guar gum using alpha galactosidase enzyme. At higher gum concentrations (0.2 and 0.3wt%), the viscosity of the emulsions containing XG/EMG gum mixtures was significantly higher (P<0.05) of all emulsions. Increasing concentrations (0-0.3wt%) of XG/EMG gum mixtures did not affect the droplet size of emulsions. Microstructure images revealed decreased flocculation at higher concentrations. Primary and secondary lipid oxidation measurements indicated a slower rate of oxidation in emulsions containing XG/EMG gum mixtures, compared to XG, guar (GG), and XG/GG gum mixtures. These results indicate that XG/EMG gum mixtures can be used in O/W emulsions to increase physical and oxidative stabilities of polyunsaturated fatty acids in foods. PMID- 27374541 TI - Changes in collagenous tissue microstructures and distributions of cathepsin L in body wall of autolytic sea cucumber (Stichopus japonicus). AB - The autolysis of sea cucumber (Stichopus japonicus) was induced by ultraviolet (UV) irradiation, and the changes of microstructures of collagenous tissues and distributions of cathepsin L were investigated using histological and histochemical techniques. Intact collagen fibers in fresh S. japonicus dermis were disaggregated into collagen fibrils after UV stimuli. Cathepsin L was identified inside the surface of vacuoles in the fresh S. japonicus dermis cells. After the UV stimuli, the membranes of vacuoles and cells were fused together, and cathepsin L was released from cells and diffused into tissues. The density of cathepsin L was positively correlated with the speed and degree of autolysis in different layers of body wall. Our results revealed that lysosomal cathepsin L was released from cells in response to UV stimuli, which contacts and degrades the extracellular substrates such as collagen fibers, and thus participates in the autolysis of S. japonicus. PMID- 27374542 TI - X-ray photoelectron spectroscopic analysis of rice kernels and flours: Measurement of surface chemical composition. AB - The objectives of this study were to evaluate the ability of X-ray photoelectron spectroscopy (XPS) to differentiate rice macromolecules and to calculate the surface composition of rice kernels and flours. The uncooked kernels and flours surface composition of the two selected rice varieties, Thadokkham-11 (TDK11) and Doongara (DG) demonstrated an over-expression of lipids and proteins and an under expression of starch compared to the bulk composition. The results of the study showed that XPS was able to differentiate rice polysaccharides (mainly starch), proteins and lipids in uncooked rice kernels and flours. Nevertheless, it was unable to distinguish components in cooked rice samples possibly due to complex interactions between gelatinized starch, denatured proteins and lipids. High resolution imaging methods (Scanning Electron Microscopy and Confocal Laser Scanning Microscopy) were employed to obtain complementary information about the properties and location of starch, proteins and lipids in rice kernels and flours. PMID- 27374543 TI - Simultaneous determination of diaveridine, trimethoprim and ormetoprim in feed using high performance liquid chromatography tandem mass spectrometry. AB - This study developed and validated a simple and reliable method for detecting and quantifying DVD, TMP and OMP in feed using dichloromethane extraction followed by HPLC-MS/MS. A matrix effect evaluation was performed using the post-extraction spiking method, and levels were less than +/-15% in all three feeds with their corresponding concentrations. LOD and LOQ, CCalpha and CCbeta were 20MUgkg(-1) and 40MUgkg(-1), 8.68-15.55MUgkg(-1) and 10.61-18.92MUgkg(-1) for all analytes, respectively. Calibration curves were linear for DVD, TMP and OMP with R(2)?0.990 and r?0.995, respectively. Recoveries of low, medium and high concentrations using the proposed method ranged from 74.4 to 105.2%. Repeatability and within laboratory reproducibility were <7.4% (RSD). The chosen seven factors had no a significant influence on robustness. The method showed good performance when it was applied to analyze other laboratory-prepared or actual feed samples. PMID- 27374544 TI - Combination of the (87)Sr/(86)Sr ratio and light stable isotopic values (delta(13)C, delta(15)N and deltaD) for identifying the geographical origin of winter wheat in China. AB - This study aims to investigate whether isotopic signatures can be used to develop reliable fingerprints for discriminating the geographical origin of Chinese winter wheat, and to evaluate the discrimination effects of delta(13)C, delta(15)N and deltaD, alone or with (87)Sr/(86)Sr. In this study, the values of delta(13)C, delta(15)N and deltaD, and the (87)Sr/(86)Sr ratios of wheat and provenance soils from three regions were determined. Significant differences were found in all parameters of wheat and (87)Sr/(86)Sr in soil extract (reflecting the bioavailable fraction of soil) among different regions. A significantly positive correlation was observed between the (87)Sr/(86)Sr ratios of wheat and soil extracts. An overall correct classification rate of 77.8% was obtained for discriminating wheat from three regions based on light stable isotopes (delta(13)C, delta(15)N, and deltaD). The correct classification rate of 98.1% could be obtained with the combination of the (87)Sr/(86)Sr ratio and the light stable isotopic values. PMID- 27374545 TI - Sensory evaluation, physicochemical properties and aroma-active profiles in a diverse collection of Chinese bayberry (Myrica rubra) cultivars. AB - The present study aimed to differentiate the flavor (taste and odor) profiles of 11 Chinese bayberry cultivars (Myrica rubra). The physicochemical analysis for taste indicated the bayberry cultivars were quite different in soluble sugars, organic acids, color, total phenolics and anthocyanin contents. Sucrose was the main soluble sugar in bayberry fruit. Principal component analysis (PCA) of physicochemical properties indicated bayberries could be divided into 5 groups, and the Bi qi cultivar contained the highest brix/acid ratio demonstrating the sweetest taste. PCA of aroma-active profile for odor (analyzed by SPME-GC-MS-O) indicated bayberries could be divided into 3 groups: alpha-pinene ("pine" odor) for group 1 (four cultivars), beta-caryophyllene and isocaryophyllene ("woody" odor) for group 2 (six cultivars), and ethyl acetate ("overripe" odor) for group 3 (one cultivar). Our research on the physicochemical and active-aroma of 11 bayberry cultivars will help to select suitable cultivars to increase consumer satisfaction. PMID- 27374546 TI - Investigation of the effect of UV-LED exposure conditions on the production of vitamin D in pig skin. AB - The dietary intake of vitamin D is currently below the recommended intake of 10 20MUg vitamin D/day. Foods with increased content of vitamin D or new products with enhanced vitamin D are warranted. Light-emitting diodes (LEDs) are a potential new resource in food production lines. In the present study the exposure conditions with ultraviolet (UV) LEDs were systematically investigated in the wavelength range 280-340nm for achieving optimal vitamin D bio fortification in pig skin. A wavelength of 296nm was found to be optimal for vitamin D3 production. The maximum dose of 20kJ/m(2) produced 3.5-4MUg vitamin D3/cm(2) pig skin. Vitamin D3 produced was independent on the combination of time and intensity of the LED source. The increased UV exposure by UV-LEDs may be readily implemented in existing food production facilities, without major modifications to the process or processing equipment, for bio-fortifying food products containing pork skin. PMID- 27374547 TI - Potential application of machine vision technology to saffron (Crocus sativus L.) quality characterization. AB - Saffron quality characterization is an important issue in the food industry and of interest to the consumers. This paper proposes an expert system based on the application of machine vision technology for characterization of saffron and shows how it can be employed in practical usage. There is a correlation between saffron color and its geographic location of production and some chemical attributes which could be properly used for characterization of saffron quality and freshness. This may be accomplished by employing image processing techniques coupled with multivariate data analysis for quantification of saffron properties. Expert algorithms can be made available for prediction of saffron characteristics such as color as well as for product classification. PMID- 27374548 TI - Enzyme-assisted extraction of phenolics from winemaking by-products: Antioxidant potential and inhibition of alpha-glucosidase and lipase activities. AB - Phenolics in food and agricultural processing by-products exist in the soluble and insoluble-bound forms. The ability of selected enzymes in improving the extraction of insoluble-bound phenolics from the starting material (experiment I) or the residues containing insoluble-bound phenolics (experiment II) were evaluated. Pronase and Viscozyme improved the extraction of insoluble-bound phenolics as evaluated by total phenolic content, antioxidant potential as determined by ABTS and DPPH assays, and hydroxyl radical scavenging capacity, reducing power as well as evaluation of inhibition of alpha-glucosidase and lipase activities. Viscozyme released higher amounts of gallic acid, catechin, and prodelphinidin dimer A compared to Pronase treatment. Furthermore, p-coumaric and caffeic acids, as well as procyanidin dimer B, were extracted with Viscozyme but not with Pronase treatment. Solubility plays an important role in the bioavailability of phenolic compounds, hence this study may assist in better exploitation of phenolics from winemaking by-products as functional food ingredients and/or supplements. PMID- 27374549 TI - Application of cavitation system to accelerate aqueous enzymatic extraction of seed oil from Cucurbita pepo L. and evaluation of hypoglycemic effect. AB - Cavitation-accelerated aqueous enzymatic extraction (CAEE) of seed oil from Cucurbita pepo was performed. An enzyme cocktail comprised of cellulose, pectinase and proteinase can work synergistically in releasing the oil. The CAEE extraction conditions were optimized by a Plackett-Burman design followed by a central composite methodology. A maximal extraction yield of 58.06% was achieved under optimal conditions of vacuum degree -0.07, enzyme amount 1.05% and extraction time 69min. As compared to soxhlet extraction (SE)-derived oil, CAEE derived oil exhibited similar physical properties and better oxidation stability. In addition, chemical composition analyzing showed that the content of linoleic acid obtained by CAEE (47.67%) was higher than that of SE (44.51%). Moreover, the IC50 of oil obtained by CAEE and SE, as measured by alpha-amylase inhibition assay, were 40.68MUg/mL and 45.46MUg/mL. All results suggest that CAEE represents an excellent alternative protocol for production of oil from oil-bearing materials. PMID- 27374550 TI - Effects of domestic processing methods on the phytochemical content of watercress (Nasturtium officinale). AB - The impact of conventional cooking and processing methods on total phenols, antioxidant activity, carotenoids and glucosinolates of watercress was evaluated. Boiling significantly decreases phenolic content, antioxidant activity and recoverable glucosinolates, however it increases the carotenoid concentrations of watercress as compared to the raw vegetable. Cooking by microwaving and steaming maintains the majority of phytochemicals in comparison to the fresh material, suggesting that they should be used as the preferred methods of watercress preparation. Boiling of watercress should be avoided to ensure maximum ingestion of watercress-derived beneficial phytochemicals. PMID- 27374551 TI - Identification of multi-insecticide residues using GC-NPD and the degradation kinetics of chlorpyrifos in sweet corn and soils. AB - Because more than one insecticide is applied to crops to protect plants from pests, an analytical multi-residue determination method was developed using gas chromatography with a nitrogen phosphorus detector (GC-NPD). The retention time for 12 insecticides was 3.7-27.7min. Under the selected conditions, the limits of detection (LOD) and quantification (LOQ) were below the maximum residue limits (MRLs) and in the range of 0.00315-0.05MUgmL(-1) and 0.01-0.165MUgmL(-1), respectively. Using GC-NPD, we investigated the dissipation dynamics and final residual levels of chlorpyrifos in sweet corn and soil and determined that the half-lives was 4-7days, that is, that chlorpyrifos is safe to use on sweet corn with a pre-harvest interval of 16-22days before harvest. These results provide new insights into chlorpyrifos degradation in plants and its environmental behavior. PMID- 27374552 TI - Soil and foliar zinc biofortification in field pea (Pisum sativum L.): Grain accumulation and bioavailability in raw and cooked grains. AB - To evaluate the potential of cooked field peas to be used in Zn biofortification programs, all combinations of soil Zn application of 0, 4 and 8mgZnSO4.7H2Okg(-1) and foliar Zn application of 0 and two sprays of 0.25% or 0.5% (w/v) ZnSO4.7H2O before flowering and at early grain-filling stage were tested. Soil Zn application increased Zn-DTPA concentration 3.7- to 5.6-times depending on the Zn soil treatments. Grain Zn concentrations higher than 60mgZnkg(-1) were obtained with all foliar Zn applications, alone or in combination with soil Zn applications, and grain Zn bioavailability was adequate (phytate:Zn ratios lower than 15). Processing (freezing and cooking) caused a decrease of about 30% in grain Zn concentration and a 17%-increase in phytate:Zn ratios (to ?9.5). The combined application of 8mgZnSO4.7H2Okg(-1) soil+0.25% (w/v) ZnSO4.7H2O foliarly could be a good option for biofortifying field peas. PMID- 27374553 TI - Multispectroscopic and docking studies on the binding of chlorogenic acid isomers to human serum albumin: Effects of esteryl position on affinity. AB - Structural differences among various dietary polyphenols affect their absorption, metabolism, and bioactivities. In this work, chlorogenic acid (CA) and its two positional isomers, neochlorogenic acid (NCA) and cryptochlorogenic acid (CCA), were investigated for their binding reactions with human serum albumin (HSA) using fluorescence, ultraviolet-visible, Fourier transform infrared and circular dichroism spectroscopies, as well as molecular docking. All three isomers were bound to HSA at Sudlow's site I and affected the protein secondary structure. CCA presented the strongest ability of hydrogen-bond formation, and both CA and NCA generated more electrostatic interactions with HSA. The albumin-binding capacity of these compounds decreased in the order CCA>NCA>CA. The compound with 4-esteryl structure showed higher binding affinity and larger conformational changes to HSA than that with 3- or 5-esteryl structures. These comparative studies on structure affinity relationship contributed to the structural modification and design of phenolic food additives or new polyphenol-like drugs. PMID- 27374554 TI - Morinda citrifolia leaf enhanced performance by improving angiogenesis, mitochondrial biogenesis, antioxidant, anti-inflammatory & stress responses. AB - Morinda citrifolia fruit, (noni), enhanced performances in athletes and post menopausal women in clinical studies. This report shows the edible noni leaves water extract enhances performance in a weight-loaded swimming animal model better than the fruit or standardized green tea extract. The 4weeks study showed the extract (containing scopoletin and epicatechin) progressively prolonged the time to exhaustion by threefold longer than the control, fruit or tea extract. The extract improved (i) the mammalian antioxidant responses (MDA, GSH and SOD2 levels), (ii) tissue nutrient (glucose) and metabolite (lactate) management, (iii) stress hormone (cortisol) regulation; (iv) neurotransmitter (dopamine, noradrenaline, serotonin) expressions, transporter or receptor levels, (v) anti inflammatory (IL4 & IL10) responses; (v) skeletal muscle angiogenesis (VEGFA) and (v) energy and mitochondrial biogenesis (via PGC, UCP3, NRF2, AMPK, MAPK1, and CAMK4). The ergogenic extract helped delay fatigue by enhancing energy production, regulation and efficiency, which suggests benefits for physical activities and disease recovery. PMID- 27374555 TI - Granular size of potato starch affects structural properties, octenylsuccinic anhydride modification and flowability. AB - Native potato starch (PS) granules were separated into three size fractions: larger than 30MUm (P-L), 15-30MUm (P-M), and smaller than 15MUm (P-S). The morphological and crystalline structure of fractionated potato starches were investigated by light and scanning electron microscopy (SEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The P-L fraction showed ellipsoidal shape and B-type X-ray pattern, whereas the P-S fraction had spherical shape and A-type pattern. The fluorophore-assisted capillary electrophoresis data showed that the P-L fraction had more B2 chains and less short A and B1 chains than the P-S counterparts. Smaller granules with larger specific surface area had higher degree of substitution when reacted with octenylsuccinic anhydride (OSA), and showed more uniform distribution of octenylsuccinate substituents. Both OSA modified and unmodified P-S samples showed higher flowability compared with the P-L counterparts. PMID- 27374556 TI - Improvement of the stability and activity of immobilized trypsin on modified Fe3O4 magnetic nanoparticles for hydrolysis of bovine serum albumin and its application in the bovine milk. AB - Trypsin (EC 3.4.21.4) was successfully immobilized on the surface of Fe3O4 magnetic nanoparticles that had been pre-treated with gallic acid (GA). Measurements of protein load by using Bradford assay and the trypsin-catalyzed hydrolysis of Nalpha-Benzoyl-dl-arginine 4-nitroanilide hydrochloride (BApNA) were made for the immobilized enzyme. By using magnetic nanoparticles, which provides easy separation and decent support material for enzyme immobilization with high surface area to volume ratio, and by employing biocompatible material gallic acid, immobilized enzyme system was synthesized along with improving trypsin activity and stability. Immobilized trypsin (TR) was more stable than the free one and demonstrated higher enzymatic activity at elevated temperatures (45 55 degrees C) and in the alkaline pH region (6-10.5). Fe3O4 NPs-GA-TR retained 92% of its initial activity after 120days of storage at 4 degrees C in sodium phosphate buffer (0.1M, pH 7.5), whereas the free trypsin maintained about 64% of its initial activity during the same storage period. In addition, activity of the immobilized trypsin was preserved 54.5% of its initial activity after eight times successive reuse. The Michaelis-Menten kinetic constant (Km) and maximum reaction velocity (Vmax) for free trypsin were 5.1mM and 23mM/min, respectively, whereas Km and Vmax values of immobilized trypsin were 7.88mM and 18.3mM/min, respectively. The performance of the immobilized trypsin was demonstrated by carrying out the hydrolysis of bovine serum albumin (BSA) within 1h, and the assay was performed by using liquid chromatography-mass spectrometry (LC-MS/MS) technique. The hydrolysis of bovine milk as a real food was investigated by immobilized trypsin using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). PMID- 27374557 TI - Chemical morphology of Areca nut characterized directly by Fourier transform near infrared and mid-infrared microspectroscopic imaging in reflection modes. AB - Fourier transform near-infrared (NIR) and mid-infrared (MIR) imaging techniques are essential tools to characterize the chemical morphology of plant. The transmission imaging mode is mostly used to obtain easy-to-interpret spectra with high signal-to-noise ratio. However, the native chemical compositions and physical structures of plant samples may be altered when they are microtomed for the transmission tests. For the direct characterization of thick plant samples, the combination of the reflection NIR imaging and the attenuated total reflection (ATR) MIR imaging is proposed in this research. First, the reflection NIR imaging method can explore the whole sample quickly to find out typical regions in small sizes. Next, each small typical region can be measured by the ATR-MIR imaging method to reveal the molecular structures and spatial distributions of compounds of interest. As an example, the chemical morphology of Areca nut section is characterized directly by the above approach. PMID- 27374558 TI - Optimization extraction of polysaccharide from Tunisian Zizyphus lotus fruit by response surface methodology: Composition and antioxidant activity. AB - Response surface methodology using a Box-Behnken design was employed to optimize extraction temperature, extraction time and ratio of water to material to obtain a maximum polysaccharide yield with high uronic acid content and antioxidant property from edible Zizyphus lotus fruit. The optimal conditions were: extraction time of 3h 15min, extraction temperature of 91.2 degrees C and water to solid ratio of 39mL/g. Under these conditions, the experimental extraction yield, uronic acid content and 2,2-diphenyl-1-picrylhydrazyl scavenging ability (IC50) were 18.88%, 41.89 and 0.518mg/mL, respectively. Chemical analysis revealed that the extract was composed of 97.92% carbohydrate of which 41.89% is uronic acid. The extracted polysaccharides, with an average molecular weight of 2720kDa, are composed of arabinose, rhamnose, glucose, fructose, galactose and xylose. Moreover, the polysaccharides exhibited a significant reducing power and anti-lipid peroxidation activities. PMID- 27374559 TI - Encapsulation of curcumin in cyclodextrin-metal organic frameworks: Dissociation of loaded CD-MOFs enhances stability of curcumin. AB - Curcumin has been successfully encapsulated in cyclodextrin-metal organic frameworks (CD-MOFs) without altering their crystallinity. The interaction between curcumin and CD-MOFs is strong through hydrogen bond type interaction between the OH group of cyclodextrin of CD-MOFs and the phenolic hydroxyl group of the curcumin. Interestingly, dissolving the curcumin loaded CD-MOFs crystals in water results in formation of a unique complex between curcumin, gammaCD and potassium cations. In fact, the initial interaction between curcumin and CD-MOF is crucial for the formation of the latter. This new complex formed in alkaline media at pH 11.5 has maximum absorbance at 520nm and emittance at 600nm. Most importantly, the stability of curcumin in this complex was enhanced by at least 3 orders of magnitude compared to free curcumin and curcumin:gamma-CD at pH 11.5. These results suggest a promising benign system of CD-MOFs, which can be used to store and stabilize curcumin for food applications. PMID- 27374560 TI - Quantifying biochemical quality parameters in carrots (Daucus carota L.) - FT Raman spectroscopy as efficient tool for rapid metabolite profiling. AB - Application of FT-Raman spectroscopy for simultaneous quantification of carotenoids, carbohydrates, polyacetylenes and phenylpropanoids with high bioactive potential was investigated in storage roots of Daucus carota. Within single FT-Raman experiment carbohydrates, carotenoids, and polyacetylenes could be reliably quantified with high coefficients of determination of R(2)>0.91. The most abundant individual representatives of each compound class could be quantified with comparably high quality resulting in R(2)=0.97 and 0.96 for alpha carotene and beta-carotene, in R(2)=0.90 for falcarindiol (FaDOH), R(2)=0.99, 0.98 and 0.96 for fructose, glucose and sucrose. In contrast, application of FT Raman spectroscopy for quantification of two laserine-type phenylpropanoids was investigated but failed due to low concentration and Raman response. Furthermore, evaluation of metabolic profiles by principle component analysis (PCA) revealed metabolic variety of carrot root composition depending on root color and botanical relationship. PMID- 27374561 TI - Influence of Tunisian aromatic plants on the prevention of oxidation in soybean oil under heating and frying conditions. AB - The aim of this study was to improve the oxidative stability of soybean oil by using aromatic plants. Soybean oil flavored with rosemary (ROS) and soybean oil flavored with thyme (THY) were subjected to heating for 24h at 180 degrees C. The samples were analyzed every 6h for their total polar compounds, anisidine values, oxidative stability and polyphenols content. The tocopherols content was determined and volatile compounds were also analyzed. After 24h of heating, the incorporation of these plants using a maceration process reduced the polar compounds by 69% and 71% respectively, in ROS and THY compared to the control. Until 6h of heating, the ROS kept the greatest oxidative stability. The use of the two extracts preserves approximately 50% of the total tocopherols content until 18h for the rosemary and 24h for the thyme flavored oils. Volatile compounds known for their antioxidant activity were also detected in the formulated oils. Aromatic plants added to the soybean oil improved the overall acceptability of potato crisps (p<0.05) until the fifteenth frying. PMID- 27374562 TI - Elemental profiling and geographical differentiation of Ethiopian coffee samples through inductively coupled plasma-optical emission spectroscopy (ICP-OES), ICP mass spectrometry (ICP-MS) and direct mercury analyzer (DMA). AB - This study was aimed to establish the elemental profiling and provenance of coffee samples collected from eleven major coffee producing regions of Ethiopia. A total of 129 samples were analyzed for forty-five elements using inductively coupled plasma (ICP)-optical emission spectroscopy (OES), ICP-mass spectrometry (MS) and direct mercury analyzer (DMA). Among the macro elements, K showed the highest levels whereas Fe was found to have the lowest concentration values. In all the samples, Ca, K, Mg, P and S contents were statistically significant (p<0.05). Micro elements showed the concentrations order of: Mn>Cu>Sr>Zn>Rb>Ni>B. Contents of the trace elements were lower than the permissible standard values. Inter-regions differentiation by cluster analysis (CA), linear discriminant analysis (LDA) and principal component analysis (PCA) showed that micro and trace elements are the best chemical descriptors of the analyzed coffee samples. PMID- 27374563 TI - Phenolic content and antioxidant activity of olive by-products and antioxidant film containing olive leaf extract. AB - The antioxidant activity of olive leaf (OL) and cake (OC) extracts with different solvents was evaluated. 70% of aqueous ethanol extract of OL was chosen as the most antioxidant extract based on antiradical activity (DPPH) (95.4+/-0.3%) and oxygen radical absorbance capacity (ORAC) (0.82+/-0.07g equivalent Trolox per g of solution) assays. This OL extract was incorporated in two multilayer materials consisting of (i) polyethylene/polyethylene (PE/PE) film and (ii) polyethylene/paper (PE/P). These multilayers were exposed to a gas stream enriched in free radicals to evaluate the scavenging capacity of both materials. PE/PE film exhibited the highest scavenging activity of free radicals (78.8%). Migration of the phenolic compounds from olive by-products into two simulants was performed and demonstrated a non-migrating behavior. The limits of detection and quantification for oleuropein were 0.5MUgkg(-1) and 1.7MUgkg(-1) and for Luteolin 7-O-glucoside 1.3MUgkg(-1) and 4.3MUg kg(-1) respectively. PMID- 27374564 TI - Multiclass pesticide analysis in fruit-based baby food: A comparative study of sample preparation techniques previous to gas chromatography-mass spectrometry. AB - With the aim to develop a new gas chromatography-mass spectrometry method to analyze 24 pesticide residues in baby foods at the level imposed by established regulation two simple, rapid and environmental-friendly sample preparation techniques based on QuEChERS (quick, easy, cheap, effective, robust and safe) were compared - QuEChERS with dispersive liquid-liquid microextraction (DLLME) and QuEChERS with dispersive solid-phase extraction (d-SPE). Both sample preparation techniques achieved suitable performance criteria, including selectivity, linearity, acceptable recovery (70-120%) and precision (?20%). A higher enrichment factor was observed for DLLME and consequently better limits of detection and quantification were obtained. Nevertheless, d-SPE provided a more effective removal of matrix co-extractives from extracts than DLLME, which contributed to lower matrix effects. Twenty-two commercial fruit-based baby food samples were analyzed by the developed method, being procymidone detected in one sample at a level above the legal limit established by EU. PMID- 27374565 TI - Protective effects of ID331 Triticum monococcum gliadin on in vitro models of the intestinal epithelium. AB - A growing interest in developing new strategies for preventing coeliac disease has motivated efforts to identify cereals with null or reduced toxicity. In the current study, we investigate the biological effects of ID331 Triticum monococcum gliadin-derived peptides in human Caco-2 intestinal epithelial cells. Triticum aestivum gliadin derived peptides were employed as a positive control. The effects on epithelial permeability, zonulin release, viability, and cytoskeleton reorganization were investigated. Our findings confirmed that ID331 gliadin did not enhance permeability and did not induce zonulin release, cytotoxicity or cytoskeleton reorganization of Caco-2 cell monolayers. We also demonstrated that ID331 omega-gliadin and its derived peptide omega(105-123) exerted a protective action, mitigating the injury of Triticum aestivum gliadin on cell viability and cytoskeleton reorganization. These results may represent a new opportunity for the future development of innovative strategies to reduce gluten toxicity in the diet of patients with gluten intolerance. PMID- 27374566 TI - Investigating the in-vitro and in-vivo flavour release from 21 fresh-cut apples. AB - In-vitro and in-vivo flavour release from 21 different apple cultivars was studied using proton transfer reaction time-of-flight mass spectrometry (PTR-ToF MS) with a focus on the relationship between texture and volatile organic compound (VOC) emission. Generally, firm-juicy cultivars had a shorter time to first swallow (Tswal) and a higher number of swallows (Nswal), while softer-mealy cultivars had a longer Tswal and a lower Nswal. Firm-juicy cultivars containing high VOC concentrations had a short time to maximum intensity (Tmax) owing to a shorter Tswal and a higher Nswal as juice was released during mastication. Swallowing increased VOC flow through the nasal cavity. These results differ from previous flavour release studies with gel/gel-like model systems as juiciness/release of fluids is not a factor in such matrices. The current study, therefore, highlights the benefits of using in-vivo analysis to gain a better understanding of flavour release in real food products. PMID- 27374567 TI - New approach to optimize near-infrared spectra with design of experiments and determination of milk compounds as influence factors for changing milk over time. AB - The optimization of near-infrared spectroscopic parameters was realized via design of experiments. With this new approach objectivity can be integrated into conventional, rather subjective approaches. The investigated factors are layer thickness, number of scans and temperature during measurement. Response variables in the full factorial design consisted of absorption intensity, signal-to-noise ratio and reproducibility of the spectra. Optimized factorial combinations have been found to be 0.5mm layer thickness, 64 scans and 25 degrees C ambient temperature for liquid milk measurements. Qualitative analysis of milk indicated a strong correlation of environmental factors, as well as the feeding of cattle with respect to the change in milk composition. This was illustrated with the aid of near-infrared spectroscopy and the previously optimized parameters by detection of altered fatty acids in milk, especially by the fatty acid content (number of carboxylic functions) and the fatty acid length. PMID- 27374568 TI - Black bean coats: New source of anthocyanins stabilized by beta-cyclodextrin copigmentation in a sport beverage. AB - Anthocyanin-rich powders and aqueous extracts, with high antioxidant activities, were obtained from black bean seed coats and applied to colour a sport beverage. Idaho and Otomi bean coats were extracted in water-citric acid 2% (1/50, w/v), stirring for 4h at 40 degrees C. Anthocyanins from Idaho and Otomi extracts (1.83mg and 1.02mg C3G/g, respectively) were applied to a commercially available sport beverage, with and without 2% beta-cyclodextrin (betaCD) under light and darkness conditions for 10days, and stored at 4 degrees C and 25 degrees C for 6weeks. At different light and storage conditions, anthocyanin degradation fitted a first-order reaction model. All bean coat anthocyanins combined with betaCD showed extended half-life (up to 13months), higher D-values (up to 43months) and fewer differences in colourimetric properties (lightness, chroma and hue angle) under darkness and 4 degrees C conditions. These black bean coat aqueous extracts and powders might represent natural alternatives to synthetic colorants, ecologically extracted, and with a high antioxidant potential. PMID- 27374569 TI - Improved non-invasive Optical Coherence Tomography detection of different engineered nanoparticles in food-mimicking matrices. AB - Food industry and regulators require fast and reliable analytical methods for quality control. This especially counts for the detection of engineered nanomaterials (ENMs) in food products. Respective EU regulation is in force, but the development of appropriate methods is still underway. This paper updates the scope of Optical Coherence Tomography (OCT) for ENM/food matrix analysis. A range of nanomaterials and composites - Au@SiO2, Ag, Ag@SiO2 and SiO2 - in a simplified food matrix was investigated. The earlier finding of linear dependencies between concentration in the dispersion and light responses could be reproduced. Being able to analyse non-invasively for a relevant industrial compound such as SiO2, makes OCT an excellent candidate for screening purposes. PMID- 27374570 TI - Use of response surface methodology for the assessment of changes in the volatile composition of Moscato bianco (Vitis vinifera L.) grape berries during ripening. AB - The changes in the volatile composition of Moscato bianco grapes were evaluated during ripening. Grape berries were sampled for five weeks (16-20 degrees Brix) and sorted for each date in ten density classes (1.05-1.12g/cm(3)). The highest total concentration of free terpenes was found at 19.3 degrees Brix; however, total concentration of the bound fraction increased significantly throughout ripening. Response surface methodology was used to assess the simultaneous effect of sampling time and berry density on the volatile composition, which was satisfactorily fitted to regression models for some key terpene compounds. Total free and bound terpenes were more affected by grape density than by sampling date. The same behaviour was observed for free and bound linalool and bound nerol, whereas the stronger effect of sampling date was exhibited for bound t rose oxide, c-rose oxide and geraniol. The results showed that the sampling strategy impacted strongly on the aroma quality of berries. PMID- 27374571 TI - Determination of the acid values of edible oils via FTIR spectroscopy based on the OH stretching band. AB - A new method for determining the acid values (AVs) of edible oils based on the OH stretching band was developed. The oil sample was diluted with carbon tetrachloride and was placed in a quartz cuvette with a thickness of 1cm to record the FTIR spectrum. The peak at 3535cm(-1), which corresponds to the OH stretch of the carboxyl group in free fatty acids, together with the peak valley at 3508cm(-1) and the spectral data in the range of 3340-3390cm(-1) were used to determine the AV of the edible oil. The excellent linear relationship between the AVs measured in this work and those measured using a titration method, with a correlation coefficient (R) of 0.9929, indicates that the present procedure can be applied as an alternative to the classic method for determining the AVs of edible oils. PMID- 27374572 TI - Antioxidative and antihypertensive activities of pig meat before and after cooking and in vitro gastrointestinal digestion: Comparison between Italian autochthonous pig Suino Nero Lucano and a modern crossbred pig. AB - The aim of this study was to evaluate and compare antioxidative and antihypertensive activities of Longissimus dorsi muscle from Suino Nero Lucano (SNL) and a modern crossbred (CG) pigs, before and after cooking and in vitro gastrointestinal digestion. Pig meat showed antioxidative and antihypertensive activities, heat treatment decreased the thiols content but at the same time increased angiotensin I-converting enzyme (ACE) inhibitory activity, and in vitro gastrointestinal digestion enhanced the biological activity of meat. Autochthonous SNL meat showed a higher nutraceutical quality compared to CG meat, highlighting a greater potential beneficial physiological effect on human health. The results of this study indicate that the pig meat, in particular autochthonous pig meat, may be considered a functional food since it is a good source of antioxidative and antihypertensive peptides. PMID- 27374573 TI - Stabilization of natural colors and nutraceuticals: Inhibition of anthocyanin degradation in model beverages using polyphenols. AB - Anthocyanins are widely used as natural colorants in foods, but they are highly susceptible to chemical degradation during storage leading to color fading. This study examined the potential of natural quillaja saponin and polyphenols (vanillin, epigallocatechin gallate, green tea extract, and protocatechualdehyde) at inhibiting color fading of anthocyanins in model beverages. The purple carrot anthocyanin (0.025%) in model beverages (citric acid, pH 3.0) containing l ascorbic acid (0.050%) degraded with a first-order reaction rate during storage (40 degrees C/7days in light). The addition of polyphenols (0.2%) delayed color fading, with the most notable improvement observed with green tea extract addition. The half-life for anthocyanin color fading increased from 2.9 to 6.7days with green tea extract. Fluorescence quenching measurements showed that the green tea extract contained components that interacted with anthocyanins probably through hydrophobic interactions. Overall, this study provides valuable information about enhancing the stability of anthocyanins in beverage systems using polyphenols. PMID- 27374574 TI - Chlorophyll catabolism in olive fruits (var. Arbequina and Hojiblanca) during maturation. AB - The central reaction of chlorophyll (chl) breakdown pathway occurring during olive fruits maturation is the cleavage of the macrocycle pheophorbide a to a primary fluorescent chl catabolite (pFCC) and it is catalyzed by two enzymes: pheophorbide a oxygenase (PaO) and red chl catabolite reductase (RCCR). In subsequent steps, pFCC is converted to different fluorescent chlorophyll catabolites (FCCs) and nonfluorescent chlorophyll catabolites (NCCs). This work demonstrated that RCCR activity of olive fruits is type II. During the study of evolution of PaO and RCCR activities through the olive fruits maturation in two varieties: Hojiblanca and Arbequina, a significant increase in PaO and RCCR activity was found in ripening stage. In addition, the profile and structure of NCCs present in epicarp of this fruit was studied using HPLC/ESI-TOF-MS. Five different NCCs were defined and for the first time the enzymatic reactions implied in chlorophyll degradations in olive fruits elucidated. PMID- 27374575 TI - Odour characteristics of seafood flavour formulations produced with fish by products incorporating EPA, DHA and fish oil. AB - Thermal degradation of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids was investigated. As a novelty, EPA, DHA or fish oil (FO) were incorporated as omega fatty acid sources into model systems containing fish powder produced via Maillard reactions. Aroma composition of the resulting products was determined and complemented with sensory evaluation. Heating of the oils led to a fast decrease of both, EPA and DHA, and to the development of characteristic volatile compounds including hexanal, 2,4-heptadienal and 4-heptenal, the most abundant being (E,E)-2,4-heptadienal (132+/-44-329+/-122MUmol/g). EPA and DHA addition to the model systems increased the concentration of these characteristic volatile compounds. However, it did not have a considerable impact on the development of characteristic Maillard reaction products, such as pyrazines and some aldehydes. Finally, the results of the sensory evaluation illustrated that panellists would chose samples fortified with FO as the ones with a more pleasant aroma. PMID- 27374576 TI - Blackberry subjected to in vitro gastrointestinal digestion affords protection against Ethyl Carbamate-induced cytotoxicity. AB - Ethyl Carbamate (EC) was detected in many fermented foods. Previous studies indicated that frequent exposure to ethyl carbamate may increase the risk to suffer from cancers. Blackberry is rich in polyphenols and possesses potent antioxidant activity. This study aims to investigate the protective effect of blackberry homogenates produced before (BH) and after in vitro simulated gastrointestinal digestion (BD) on EC-induced toxicity in Caco-2 cells. Our results showed that blackberry homogenates after digestion (BD) was more effective than that before digestion (BH) in ameliorating EC-induced toxicity in Caco-2 cells. Further investigation revealed that BD remarkably attenuated EC induced toxicity through restoring mitochondrial function, inhibiting glutathione depletion and decreasing overproduction of intracellular reactive oxygen species. Additionally, LC-MS result implied that the better protective capacity of BD may be related to the increased content of two anthocyanins (cyanidin-3-glucoside and cyanidin-3-dioxalyglucoside). Overall, the present study may give implication to prevent EC-induced health problem. PMID- 27374577 TI - Quality characteristics and antioxidant properties of Turkish monovarietal olive oils regarding stages of olive ripening. AB - The aim of this study was to discriminate the extra virgin olive oils (EVOO) based on quality characteristics, chemical composition and antioxidant activity according to ripening stages of olives. Two different olive varieties (Memecik and Gemlik) were obtained at different stages of ripening based on skin color (green, purple and black). Quality properties of olive oils; free fatty acidity, peroxide value, K232 and K270, purity properties; fatty acid and triacylglycerol (TAG) composition and antioxidant compounds like total phenol, carotenoid and chlorophyll content and antioxidant activity (oxidative stability, ABTS radical scavenging activity) analyses were performed. Higher amount of oleic, linoleic and palmitic acids were observed in olive oils. Oleic acid amount of olive oils decreased, linoleic acid increased with ripening. The most abundant TAG of olive oils were ECN 48, OOO, SLO+POO, ECN 46 and LOO/PLO. Olive oils were clearly classified by principal component analysis based on fatty acid and TAG composition. PMID- 27374578 TI - Monitoring and determination of sulfonamide antibiotics (sulfamethoxydiazine, sulfamethazine, sulfamethoxazole and sulfadiazine) in imported Pangasius catfish products in Thailand using liquid chromatography coupled with tandem mass spectrometry. AB - This research aimed to monitor the concentrations of sulfamethoxydiazine (SMD), sulfamethazine (SMT), sulfamethoxazole (SMX) and sulfadiazine (SDZ) in imported Pangasius catfish products in Thailand. The residues of the four sulfonamides (SAs) were analyzed by extraction process and liquid chromatography coupled with tandem mass spectrometry. The highest concentrations found were 10.97ng/g for SMD, 6.23ng/g for SMT, 11.13ng/g for SDZ and 245.91ng/g for SMX, which was higher than the European Union (EU) standard (100ng/g). Moreover, all samples contaminated with SMX also contained SMT, indicating that more than one antibiotic was used for production in the country of origin. Because Thai standards for antibiotics in food have not been completely set, all contaminated discovered would not be considered to be an illegal food, in which antibiotic residues may affect human health in the long term. Therefore, antibiotic residues in Pangasius catfish products should be continually regulated and monitored. PMID- 27374579 TI - Comparison of the regiospecific distribution from triacylglycerols after chemical and enzymatic interesterification of high oleic sunflower oil and fully hydrogenated high oleic sunflower oil blend by carbon-13 nuclear magnetic resonance. AB - The nutritional and organoleptic attributes of oils can proceed via interesterification of oils blends catalyzed by enzymes or chemicals. Enzymatic interesterification processes are preferred due the regiospecific outcome. Traditionally, monitoring of distribution of fatty acids (FA) in glycerol backbone is performed by enzymatic and chromatographic methods that are time consuming, involving a series of chemical manipulations employing large volumes of organic solvents. Alternatively, carbon-13 nuclear magnetic resonance ((13)C NMR) is a fast and reliable technique that could be applied to determine the saturated and unsaturated FA distribution of the triacylglycerols (TAGs) present in high oleic sunflower oil (SO) and fully hydrogenated high oleic sunflower oil (HSO) blends and their interesterification products. The enzymatic interesterification was conducted employing the immobilized lipase from Thermomyces lanuginosus (Lipozyme TL IM), the results show that the process was not completely regiospecific at sn-1,3 positions, due to the spontaneous acyl migration from position sn-2 to sn-1,3. PMID- 27374580 TI - Physicochemical and functional properties of protein isolate produced from Australian chia seeds. AB - Protein was isolated from Australian chia seeds and converted to powders using spray, freeze and vacuum drying methods, to investigate the effect of drying methods on physicochemical and functional attributes of chia-seed protein isolate (CPI). It was found that there was no significant difference in the proximate composition; however vacuum dried CPI (VDCPI) had the highest bulk density and oil absorption capacity, whereas spray dried powder (SDCPI) demonstrated the highest solubility, water absorption capacity and lowest surface hydrophobicity. Solubility of all powders was higher at elevated temperature and alkaline pH. Foaming capacity and foam stability of CPI were found to increase with increasing pH and protein concentration. SDCPI was the least denatured and VDCPI the most denatured, demonstrating the poorest solubility and foaming properties of the latter. These findings are expected to be useful in selection of a drying process to yield chia seed protein powders with more desirable functionality. PMID- 27374581 TI - Thermal processing effects on peanut allergen Ara h 2 allergenicity in mice and its antigenic epitope structure. AB - Ara h 2 was purified from peanuts that were thermally treated by various processes, including boiling, glycation, frying and roasting. The allergenicity of Ara h 2 in Balb/c mice and the influence of thermal processing on the structural characteristics, and binding capacity of three core antigenic epitopes were studied. The results demonstrated that boiling, glycation and frying induced the down-regulation of the allergenicity of Ara h 2 in Balb/c mice, the collapse of its tertiary/secondary structure, and a reduction in the core epitope binding capacity; roasting showed a comparable allergenicity and the weakest inhibitory effect on core epitope binding capacity. These results indicate that thermal processing causes alteration of the protein structure and core epitopes of Ara h 2, and may affect its allergenicity. PMID- 27374582 TI - Effect of heating/reheating of fats/oils, as used by Asian Indians, on trans fatty acid formation. AB - Heating/frying and reuse of edible fats/oils induces chemical changes such as formation of trans fatty acids (TFAs). The aim of this study was to investigate the effect of heating/frying on formation of TFAs in fats/oils. Using gas chromatography with flame ionisation detector, TFA was estimated in six commonly used fat/oils in India (refined soybean oil, groundnut oil, olive oil, rapeseed oil, clarified butter, partially hydrogenated vegetable oil), before and after subjecting them to heating/frying at 180 degrees C and 220 degrees C. All six fats/oils subjected to heating/frying demonstrated an increase in TFAs (p<0.001), saturated fatty acids (p<0.001) and decrease in cis-unsaturated fatty acids (p<0.001). The absolute increase in TFA content of edible oils (after subjecting to heating/reheating) ranged between 2.30+/-0.89g/100g and 4.5+/-1.43g/100g; amongst edible fats it ranged between 2.60+/-0.38g/100g and 5.96+/-1.94g/100g. There were no significant differences between the two treatment groups (heating and frying; p=0.892). Considering the undesirable health effects of TFA, appropriate guidelines for heating/re-frying of edible fats/oils by Asian Indians should be devised. PMID- 27374583 TI - Microwave-assisted drying of blueberry (Vaccinium corymbosum L.) fruits: Drying kinetics, polyphenols, anthocyanins, antioxidant capacity, colour and texture. AB - The aim of the study was to evaluate the effect of hot air convective drying (HACD), microwave vacuum drying (MWVD) and their combination (HACD+MWVD) on the drying kinetics, colour, total polyphenols, anthocyanins antioxidant capacity and texture of frozen/thawed blueberries. Drying resulted in reduction of total polyphenols content and antioxidant capacity (69 and 77%, respectively). The highest content of total polyphenols was noted after HACD at 90 degrees C. Lower air temperature and prolonged exposure to oxygen resulted in greater degradation of polyphenols and antioxidant capacity. Drying processes caused a significant decrease (from 70 to 95%) in the content of anthocyanins. The highest content of anthocyanins and the strongest antioxidant capacity was found in blueberries dried using HACD at 90 degrees C+MWVD. Among drying methods, HACD at 90 degrees C+MWVD satisfied significant requirements for dried fruits i.e. short drying time and improved product quality. PMID- 27374584 TI - Effect of pecan phenolics on the release of nitric oxide from murine RAW 264.7 macrophage cells. AB - Inflammation is linked to numerous chronic disease states. Phenolic compounds have attracted attention because a number of these compounds possess anti inflammatory properties. A phenolic crude extract was prepared from pecans and separated by Sephadex LH-20 column chromatography into low- and high-molecular weight (LMW/HMW) fractions. Anti-inflammatory properties of these fractions were assessed in LPS-stimulated RAW 264.7 murine macrophage cells. NO and reactive oxygen species (ROS) production was monitored after 3 different experimental protocols: (1) pre-treatment with Escherichia coli O111:B4 lipopolysaccharide (LPS); (2) pre-treatment with a pecan crude extract and its fractions; and (3) co incubation of LPS with a pecan crude extract and its fractions. The LMW fraction displayed a dose-dependent decrease in NO production and a significant decrease from the LPS control in ROS production when cells were either co-incubated with or pre-treated with LPS. The phenolics were characterized by HPLC to help identify those responsible for the observed effect. PMID- 27374585 TI - A highly sensitive impedimetric label free immunosensor for Ochratoxin measurement in cocoa beans. AB - In this work the development and optimization of an impedimetric label free immunosensor for the detection of Ochratoxin A (OTA) is reported. Two antibody immobilization methods (oriented and not oriented) were compared highlighting a lower limit of detection (5pg/ml) for the not oriented immobilization but a closer linear range in contrast to oriented anti-OTA immunosensors which showed linearity in the range of 0.01-5ng/mL OTA. The analysis of the Atomic Force Microscopy (AFM) images showed two different nanostructures indicating that the use of oriented immobilization created a more ordered and highly dense antibody surface. Finally the oriented immunosensor was used to quantify OTA in spiked cocoa bean samples and the results were compared with those registered with competitive ELISA kit. The immunosensor was sensitive to OTA lower than 2MUg/kg that represents the lower acceptable limit of OTA established by European legislation for the common food products. PMID- 27374586 TI - Antiproliferative activity of buttermilk lipid fractions isolated using food grade and non-food grade solvents on human cancer cell lines. AB - Buttermilk is a dairy by-product with a high content of milk fat globule membranes (MFGMs), whose protein constituents are reported to be antiproliferative. Lipids represent about half of the composition of MFGM. The aim of this study was to isolate buttermilk lipid fractions and evaluate their potential antiproliferative effect. Selective extraction with food grade or non food grade solvents was performed. Antiproliferative effectiveness of lipid extracts and their neutral and polar fractions was evaluated on nine human cancer cell lines. Fractions obtained using food grade ethanol gave a higher yield than those obtained using non-food grade solvents, and they effectively inhibited cell viability of the cancer cell lines investigated. These fractions, rich in phospho and sphingolipids, were strongly antiproliferative against human ovary and colon cancer cells. This observation allowed us to hypothesize further analyses aimed at promoting the use of buttermilk polar lipid fractions as functional food additives. PMID- 27374587 TI - Guarana (Paullinia cupana) seeds: Selective supercritical extraction of phenolic compounds. AB - Approximately 70% of the Brazilian production of guarana (Paullinia cupana) seeds is absorbed by the beverage industries. Guarana has several pharmacological properties: energy stimulant, antimicrobial, chemoprophylactic, antigenotoxic, antidepressive, anxiolytic, and anti-amnesic effects. Supercritical carbon dioxide extraction of bioactive compounds from guarana seeds was carried out and optimized by an orthogonal array design (OA9(3(4))). The factors/levels studied were: modifier(s) (ethanol and/or methanol), extraction time (20, 40, and 60min), temperature (40, 50, and 60 degrees C), and pressure (100, 200, and 300bar). The statistical design was repeated with increasing proportions of modifiers. The percentage of modifier used was proportional to the amount of polar compounds extracted. The best conditions for the supercritical extraction, based on the content of polyphenols, epicatechin/catechin quantification, yield and operating cost, proved to be: 40% ethanol:methanol during 40min, under 40 degrees C, and 100bar. The temperature had a significant effect on the total phenolic content. PMID- 27374588 TI - Preparative separation of grape skin polyphenols by high-speed counter-current chromatography. AB - To develop an efficient method for large preparation of various individual polyphenols from white grape skins (Fernao Pires; Vitis vinifera) by preparative high-speed counter-current chromatography (HSCCC) and preparative-HPLC, an optimized preparative HSCCC condition with two-phase solvent system composed of Hex-EtOAc-H2O (1:50:50, v/v) was used to separate grape skin polyphenols into various fractions. Both the tail-head and head-tail elution modes were used with a flow rate of 3.0ml/min and a rotary speed of 950rpm. Afterwards, a preparative HPLC separation was applied to isolate individual polyphenols in each of the fractions from HSCCC. Total of 7 fractions (Fraction A to G) were obtained from grape skin extract by HSCCC. After preparative-HPLC isolation, fifteen individual compounds were obtained, most of which presented high yields and purity (all over 90%). The HSCCC method followed with preparative-HPLC appeared to be convenient and economical, constituting an efficient strategy for the isolation of grape skin polyphenols. PMID- 27374589 TI - Evolution of protein bound Maillard reaction end-products and free Amadori compounds in low lactose milk in presence of fructosamine oxidase I. AB - Thermal treatments and storage influence milk quality, particularly in low lactose milk as the higher concentration of reducing sugars can lead to the increased formation of the Maillard reaction products (MRPs). The control of the Amadori products (APs) formation is the key step to mitigate the Maillard reaction (MR) in milk. The use of fructosamine oxidases, (Faox) provided promising results. In this paper, the effects of Faox I were evaluated by monitoring the concentration of free and bound MRPs in low lactose milk during shelf life. Results showed that the enzyme reduced the formation of protein-bound MRPs down to 79% after six days at 37 degrees C. Faox I lowered the glycation of almost all the free amino acids resulting effective on basic and polar amino acids. Data here reported corroborate previous findings on the potentiality of Faox enzymes in controlling the early stage of the MR in foods. PMID- 27374590 TI - Characterisation of minor components in vegetable oil by comprehensive gas chromatography with dual detection. AB - The profile of minor compounds, such as alcohols, sterols, free and alkyl fatty acids, waxes, etc., was investigated in different vegetable oils by a comprehensive gas chromatographic system, coupled with a simultaneous dual detection (flame ionisation detector and mass spectrometer) for quantitative and qualitative purposes. Such a system generated a unique two-dimensional chromatogram to be used as a chemical fingerprint. Multi-level information, due not only to a more "comprehensive" preparation technique, but also thanks to the exploitation of a more powerful and sensitive analytical determination allowed the extrapolation of diagnostic information from the minor components profile of different vegetable oils, along with their characteristic profile. Furthermore, an admixture of an extra virgin olive oil with a low amount of sunflower and palm oils was evaluated, attesting to the powerful diagnostic information provided by the proposed approach. PMID- 27374591 TI - Green tea flavour determinants and their changes over manufacturing processes. AB - Flavour determinants in tea infusions and their changes during manufacturing processes were studied using Camellia sinensis cultivars 'Bai-Sang Cha' ('BAS') possessing significant floral scents and 'Fuding-Dabai Cha' ('FUD') with common green tea odour. Metabolite profiling based on odour activity threshold revealed that 'BAS' contained higher levels of the active odorants beta-ionone, linalool and its two oxides, geraniol, epoxylinalool, decanal and taste determinant catechins than 'FUD' (p<0.05). Enhanced transcription of some terpenoid and catechin biosynthetic genes in 'BAS' suggested genetically enhanced production of those flavour compounds. Due to manufacturing processes, the levels of linalool and geraniol decreased whereas those of beta-ionone, linalool oxides, indole and cis-jasmone increased. Compared with pan-fire treatment, steam treatment reduced the levels of catechins and proportion of geraniol, linalool and its derivatives, consequently, reducing catechin-related astringency and monoterpenol-related floral scent. Our study suggests that flavour determinant targeted modulation could be made through genotype and manufacturing improvements. PMID- 27374592 TI - In-vitro digestibility, rheology, structure, and functionality of RS3 from oat starch. AB - Starches isolated from three different varieties of oat were modified with dual autoclaving-retrogradation treatment to make modified food starches with high contents of type 3 resistant starch (RS3). FT-IR spectroscopy showed increase in the ratio of intensity of 1047cm(-1)/1022cm(-1) on treatment. Morphology of the oat starches changed into a continuous network with increased values for onset temperature (To), peak temperature (Tp), and conclusion temperature (Tc). XRD showed an additional peak at 13 degrees and increase in peak intensity at 20 degrees inclusive of the major X-ray diffraction peaks which reflects formation of amylose-lipid complex from dual autoclaving-retrogradation cycle. Peaks at 13 degrees and 20 degrees are the typical peaks of the V-type pattern. Rheological analysis suggested that retrogradated oat starches showed shear thickening behavior as revealed from Herschel-Bulkely model and frequency sweep. PMID- 27374593 TI - Fully-automated in-syringe dispersive liquid-liquid microextraction for the determination of caffeine in coffee beverages. AB - A novel fully-automated magnetic stirring-assisted lab-in-syringe analytical procedure has been developed for the fast and efficient dispersive liquid-liquid microextraction (DLLME) of caffeine in coffee beverages. The procedure is based on the microextraction of caffeine with a minute amount of dichloromethane, isolating caffeine from the sample matrix with no further sample pretreatment. Selection of the relevant extraction parameters such as the dispersive solvent, proportion of aqueous/organic phase, pH and flow rates have been carefully evaluated. Caffeine quantification was linear from 2 to 75mgL(-1), with detection and quantification limits of 0.46mgL(-1) and 1.54mgL(-1), respectively. A coefficient of variation (n=8; 5mgL(-1)) of a 2.1% and a sampling rate of 16h( 1), were obtained. The procedure was satisfactorily applied to the determination of caffeine in brewed, instant and decaf coffee samples, being the results for the sample analysis validated using high-performance liquid chromatography. PMID- 27374594 TI - Sweetness-induced activation of membrane dipole potential in STC-1 taste cells. AB - The biological functions of cell membranes strongly influence the binding and transport of molecular species. We developed STC-1 cell line stably expressing the sweet taste receptor (T1R2/T1R3), and explored the possible correlation between sweeteners and membrane dipole potential of STC-1 cells. In this study, sweetener-induced dipole potential activation was elucidated using a fluorescence based measurement technique, by monitoring the voltage sensitive probe Di-8 ANEPPS using a dual wavelength ratiometric approach. It indicated that the presence of sweeteners resulted in cell membrane dipole potential change, and interaction of artificial sweeteners with taste cells resulted in a greater reduction in potential compared with natural sweeteners. Our work presents a newly developed approach using a fluorescence-based measurement technique to study sweetener-induced dipole potential activation of STC-1 cells. This new approach could be used as a complementary tool to study the function of sweet taste receptors or other GPCRs and helps to understand the basis sweetness mechanism. PMID- 27374595 TI - Characterization of substituted aryl meroterpenoids from red seaweed Hypnea musciformis as potential antioxidants. AB - The ethyl acetate fraction of red seaweed Hypnea musciformis was purified to yield three substituted aryl meroterpenoids, namely, 2-(tetrahydro-5-(4 hydroxyphenyl)-4-pentylfuran-3-yl)-ethyl-4-hydroxybenzoate (1), 2-2-[(4 hydroxybenzoyl)-oxy]-ethyl-4-methoxy-4-2-[(4-methylpentyl)oxy]-3,4-dihydro-2H-6 pyranylbutanoic acid (2) and 3-((5-butyl-3-methyl-5,6-dihydro-2H-pyran-2-yl) methyl)-4-methoxy-4-oxobutyl benzoate (3). The structures of these compounds, as well as their relative stereochemistries, were confirmed by exhaustive NMR spectroscopic data analyses. Compound 1 exhibited similar 2,2' diphenylpicrylhydrazyl radical inhibiting and Fe(2+) ion chelating activities (IC50 25.05 and 350.7MUM, respectively) as that of commercial antioxidant gallic acid (IC50 32.3 and 646.6MUM, respectively), followed by 3 (IC50 231.2 and 667.9MUM, respectively), and 2 (IC50 322.4 and 5115.3MUM, respectively), in descending order of activities. Structure-activity relationship analysis revealed that the antioxidant activities of these compounds were directly proportional to the steric and hydrophobic parameters. The seaweed derived aryl meroterpenoids might serve as potential lead antioxidative molecules for use in pharmaceutical and food industries. PMID- 27374596 TI - Effects of Hofmeister salt series on gluten network formation: Part I. Cation series. AB - Different cationic salts were used to investigate the effects of the Hofmeister salt series on gluten network formation. The effects of cationic salts on wheat flour dough mixing properties, the rheological and the chemical properties of the gluten extracted from the dough with different respective salts, were investigated. The specific influence of different cationic salts on the gluten structure formation during dough mixing, compared to the sodium ion, were determined. The effects of different cations on dough and gluten of different flours mostly followed the Hofmeister series (NH4(+), K(+), Na(+), Mg(2+) and Ca(2+)). The impacts of cations on gluten structure and dough rheology at levels tested were relatively small. Therefore, the replacement of sodium from a technological standpoint is possible, particularly by monovalent cations such as NH4(+), or K(+). However the levels of replacement need to take into account sensory attributes of the cationic salts. PMID- 27374597 TI - Effects of Hofmeister salt series on gluten network formation: Part II. Anion series. AB - Different anion salts from the Hofmeister series were used to investigate their effects on gluten network formation. The effects of these anion salts on the mixing properties of the dough and the rheological and chemical properties of gluten samples extracted from the dough with these respective salts were compared. The aim of this work was to determine how different anion salts influence the formation of the gluten structure during dough mixing. It was found that the Hofmeister anion salts affected the gluten network formation by interacting directly with specific amino acid residues that resulted in changes in gluten protein composition, specifically the percentage of the unextractable polymeric protein fractions (%UPP). These changes consequently led to remarkable differences in the mixing profiles and microstructural features of the dough, small deformation rheological properties of the gluten and a strain hardening behaviour of both dough and gluten samples. PMID- 27374598 TI - Determination of Sudan I in drinks containing Sunset yellow by adsorptive stripping voltammetry. AB - An efficient, fast and sensitive method for the determination of Sudan I (SI) in drinks containing Sunset yellow (Sy) is developed and validated using an adsorptive stripping voltammetric procedure. Sy is currently added to a large number of foods; however during their synthesis SI may be produced. The determination is based on adsorption of Sy and SI onto HMDE and later reduction of the azo group at -0.71 and -0.82V, respectively. Using the best set of the experimental conditions (pH 12.3; Eads: -0.40V) for the determination of SI in Sy, a linear response for SI in the concentration range 0.5-27.2MUgL(-1) was found, with a detection limit of 1.5MUgL(-1) in a tads of only 30s. The method was applied to the determination of SI in commercial drinks with satisfactory results. The presence of SI was confirmed by mass spectrometry. PMID- 27374599 TI - Different coatings for the HS-SBSE grape volatile analysis in model solution: Preliminary results. AB - Head space stir bar sorptive extraction (HS-SBSE) was used to evaluate the efficacy of two stir bar coatings, poly(ethylene glycol) (PEG)-modified silicone (EG-Silicone) and polyacrylate (PA), in comparison with polydimethyl siloxane (PDMS) coating, to assess volatiles in model wine solutions. In addition, two temperatures (0 degrees C and 25 degrees C) of the injection system (CIS) were compared. This was performed to propose an analytical procedure cheaper and faster respect to traditional extractive methods and environmental friendly, avoiding the use of large amounts of solvents and high-energy consumption for cooling. Fifteen grape volatiles with different polarities, known to have an important impact on varietal wine aroma, were tested. The affinity of each tested molecule to the new coatings was assessed. The PDMS coating showed higher relative areas for terpenes (beta-citronellol, geraniol, linalool and alpha terpineol) and norisoprenoids (beta-ionone), especially when the CIS temperature was set at 25 degrees C. C6 compounds such as 1-hexanol, (E)-2-hexenal, (E)-2 hexen-1-ol, (Z)-3-hexen-1-ol, and benzaldehyde and eugenol, obtained greater area response using EG-Silicone and PA coatings, regardless the temperatures. The memory effect of each coating type was studied; EG Silicone and PA coatings showed a higher memory effect for a certain compounds, probably due to the lower desorption temperature that EG Silicone and PA coatings can be submitted to, respect to PDMS (220 degrees C the former two, 295 degrees C the latter). PMID- 27374600 TI - Validation of a rapid conductimetric test for the measurement of wine tartaric stability. AB - This work was aimed at optimizing a rapid and reproducible conductivity test for the evaluation of wine tartaric stability, in order to improve the practices for the prevention of tartaric precipitations during bottle aging. The test consists in measuring the drop of conductivity in wines kept under stirring for a fixed time, at low temperature, after the addition of micronized potassium bitartrate crystals (KHT). An experimental design was planned to study three factors affecting the test: temperature, duration and dose of added potassium bitartrate. A standard protocol was defined to produce a micronized potassium bitartrate starting from available commercial products, since the dimensions of the crystals can affect the final conductivity values. After the choice of the best conditions the method was validated. Two different stability thresholds were defined for white wines and for red/rose wines by comparing the results of the mini-contact test with those of the cold test. PMID- 27374601 TI - Polyphenolic responses of grapevine berries to light, temperature, oxidative stress, abscisic acid and jasmonic acid show specific developmental-dependent degrees of metabolic resilience to perturbation. AB - Grape-berries are exposed to a plethora of abiotic and biotic stimuli during their development. The developmental and temporal regulation of grape berry polyphenol metabolism in response to various cues was investigated using LC-QTOF MS based metabolite profiling. High light (2500MUmolm(-2)s(-1)), high temperature (40 degrees C), jasmonic acid (200MUM), menadione (120MUM) and abscisic acid (3.026mM) treatments were applied to detached berries. Greater magnitudes of metabolite fluctuations characterize the pre-veraison berries than the veraison stage in response to the treatments. Furthermore, a tighter co-response of metabolic processes was shown at veraison, likely supporting the resilience to change in response to stress. High temperature and ABA treatments led to greater magnitudes of change during the course of the experiment. The present study demonstrates the occurrence of differential patterns of metabolic responses specific to individual cues and berry developmental stage, which in the field are commonly associated and thus hardly discernable. PMID- 27374602 TI - Rapid fingerprinting of white wine oxidizable fraction and classification of white wines using disposable screen printed sensors and derivative voltammetry. AB - This work describes the application of disposable screen printed carbon paste sensors for the analysis of the main white wine oxidizable compounds as well as for the rapid fingerprinting and classification of white wines from different grape varieties. The response of individual white wine antioxidants such as flavanols, flavanol derivatives, phenolic acids, SO2 and ascorbic acid was first assessed in model wine. Analysis of commercial white wines gave voltammograms featuring two unresolved anodic waves corresponding to the oxidation of different compounds, mostly phenolic antioxidants. Calculation of the first order derivative of measured current vs. applied potential allowed resolving these two waves, highlighting the occurrence of several electrode processes corresponding to the oxidation of individual wine components. Through the application of Principal Component Analysis (PCA), derivative voltammograms were used to discriminate among wines of different varieties. PMID- 27374603 TI - Corrigendum to "Enhancement of the gelation properties of hairtail (Trichiurus haumela) muscle protein with curdlan and transglutaminase" [Food Chem. 176 (2015) 115-122]. PMID- 27374605 TI - Frequency of Methamphetamine Use as a Major Contributor Toward the Severity of Cardiomyopathy in Adults <=50 Years. AB - Methamphetamine is one of the most commonly abused illegal drugs in the United States. Health care providers are commonly faced with medical illness caused by methamphetamine. This study investigates the impact of methamphetamine use on the severity of cardiomyopathy and heart failure in young adults. This retrospective study analyzed patients seen at Arrowhead Regional Medical Center from 2008 to 2012. Patients were between 18 and 50 years old. All patients had a discharge diagnosis of cardiomyopathy or heart failure. The severity of disease was quantified by left ventricular systolic dysfunction: heart failure with preserved ejection fraction to mildly reduced if ejection fraction was >40% and moderate to severely depressed if ejection fraction was <=40%. Methamphetamine abuse was determined by a positive urine drug screen or per documented history. Of the 590 patients, 223 (37.8%) had a history of methamphetamine use. More than half the population was men (n = 389, 62.3%); 41% was Hispanic (n = 243), 25.8% was Caucasian (n = 152), and 27.8% was African-American (n = 164); 60.9% were in the age range of 41 to 50 years (n = 359). Patients with a history of methamphetamine use had increased odds (odds ratio = 1.80, 95% confidence interval 1.27 to 2.57) of having a moderately or severely reduced ejection fraction. Additionally, men were more likely (odds ratio 3.13, 95% confidence interval 2.14 to 4.56) to have worse left ventricular systolic dysfunction. In conclusion, methamphetamine use was associated with an increased severity of cardiomyopathy in young adults. PMID- 27374604 TI - Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioning. AB - Enduring memories of sensory cues associated with drug intake drive addiction. It is well known that stressful experiences increase addiction vulnerability. However, it is not clear how repeated stress promotes learning of cue-drug associations, as repeated stress generally impairs learning and memory processes unrelated to stressful experiences. Here, we show that repeated social defeat stress in rats causes persistent enhancement of long-term potentiation (LTP) of NMDA receptor-mediated glutamatergic transmission in the ventral tegmental area (VTA). Protein kinase A-dependent increase in the potency of inositol 1,4,5 triphosphate-induced Ca(2+) signaling underlies LTP facilitation. Notably, defeated rats display enhanced learning of contextual cues paired with cocaine experience assessed using a conditioned place preference (CPP) paradigm. Enhancement of LTP in the VTA and cocaine CPP in behaving rats both require glucocorticoid receptor activation during defeat episodes. These findings suggest that enhanced glutamatergic plasticity in the VTA may contribute, at least partially, to increased addiction vulnerability following repeated stressful experiences. PMID- 27374606 TI - Diagnosis, Clinical Course, and 1-Year Outcome in Patients Hospitalized for Heart Failure With Preserved Ejection Fraction (from the Polish Cohort of the European Society of Cardiology Heart Failure Long-Term Registry). AB - Compared with heart failure (HF) with reduced ejection fraction (HF-REF), the diagnosis of HF with preserved EF (HF-PEF) is more challenging. The aim of the study was to assess the prevalence of HF-PEF among patients hospitalized for HF, to evaluate the pertinence of HF-PEF diagnosis and to compare HF-PEF and HF-REF patients with respect to outcomes. The analysis included 661 Polish patients hospitalized for HF, selected from the European Society of Cardiology (ESC)-HF Long-Term Registry. Patients with an EF of >=50% were included in the HF-PEF group and patients with an EF of <50% - in the HF-REF group. The primary end point was all-cause death at 1 year. The secondary end point was a composite of all-cause death and rehospitalization for HF at 1 year. HF-PEF was present in 187 patients (28%). Of those 187 patients, mitral inflow pattern was echocardiographically assessed in 116 patients (62%) and classified as restrictive/pseudonormal in 37 patients (20%). Compared with HF-REF subjects, patients with HF-PEF were older, more often female, and had a higher prevalence of hypertension, atrial fibrillation and sleep apnea. Despite lower B-type natriuretic peptide concentrations and lower prevalence of moderate-to-severe mitral regurgitation in patients with HF-PEF, congestive symptoms at admission were as severe as in patients with HF-REF. There were no significant differences in in-hospital mortality between the HF groups. One-year mortality was high in both groups (17% in HF-PEF vs 21% in HF-REF, p = 0.22). There was a trend toward a lower frequency of the secondary end point in the HF-PEF group (32% vs 40%, p = 0.07). In conclusion, in clinical practice, even easily obtainable echocardiographic indexes of diastolic dysfunction are relatively rarely acquired. One-year survival rate of patients with HF-PEF is not significantly better than that of patients with HF-REF. PMID- 27374607 TI - Mediating and moderating processes in the relationship between multicultural ideology and attitudes towards immigrants in emerging adults. AB - Few studies examine intercultural relations in emerging adulthood. Framed from the perspective of the Mutual Intercultural Relations in Plural Societies (MIRIPS) project, the current paper examined the mediating role of tolerance and perceived consequences of immigration in the relationship between multicultural ideology and attitudes towards immigrants. Additionally, the moderating role of context was analysed. A two-group structural equation modelling was performed on data collected from 305 Italian emerging adults living both in northern and in southern Italy with different socio-political climates towards immigrants. In both groups, tolerance and perceived consequences of immigration mediated the relationship between multicultural ideology and attitudes towards immigrants. Also, this indirect relationship was significantly higher for the northern than southern Italians. These findings provide provisional evidence of mediating and moderating processes in the relationship between multicultural ideology and attitudes towards immigrants and suggest important implications for practitioners interested in promoting intercultural relations among emerging adults. PMID- 27374608 TI - Professor Emeritus E. Wynn Jones MRCVS, FRCVS, PhD. PMID- 27374609 TI - Following the Reduction of Oxygen on TiO2 Anatase (101) Step by Step. AB - We have investigated the reaction between O2 and H2O, coadsorbed on the (101) surface of a reduced TiO2 anatase single crystal by scanning tunneling microscopy, density functional theory, temperature-programmed desorption, and X ray photoelectron spectroscopy. While water adsorbs molecularly on the anatase (101) surface, the reaction with O2 results in water dissociation and formation of terminal OH groups. We show that these terminal OHs are the final and stable reaction product on reduced anatase. We identify OOH as a metastable intermediate in the reaction. The water dissociation reaction runs as long as the surface can transfer enough electrons to the adsorbed species; the energy balance and activation barriers for the individual reaction steps are discussed, depending on the number of electrons available. Our results indicate that the presence of donor dopants can significantly reduce activation barriers for oxygen reduction on anatase. PMID- 27374610 TI - High-resolution genetic maps of Lotus japonicus and L. burttii based on re sequencing of recombinant inbred lines. AB - Recombinant inbred lines (RILs) derived from bi-parental populations are stable genetic resources, which are widely used for constructing genetic linkage maps. These genetic maps are essential for QTL mapping and can aid contig and scaffold anchoring in the final stages of genome assembly. In this study, two Lotus sp. RIL populations, Lotus japonicus MG-20 * Gifu and Gifu * L. burttii, were characterized by Illumina re-sequencing. Genotyping of 187 MG-20 * Gifu RILs at 87,140 marker positions and 96 Gifu * L. burttii RILs at 357,973 marker positions allowed us to accurately identify 1,929 recombination breakpoints in the MG-20 * Gifu RILs and 1,044 breakpoints in the Gifu * L. burttii population. The resulting high-density genetic maps now facilitate high-accuracy QTL mapping, identification of reference genome mis-assemblies, and characterization of structural variants. PMID- 27374611 TI - An automated system for evaluation of the potential functionome: MAPLE version 2.1.0. AB - Metabolic and physiological potential evaluator (MAPLE) is an automatic system that can perform a series of steps used in the evaluation of potential comprehensive functions (functionome) harboured in the genome and metagenome. MAPLE first assigns KEGG Orthology (KO) to the query gene, maps the KO-assigned genes to the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional modules, and then calculates the module completion ratio (MCR) of each functional module to characterize the potential functionome in the user's own genomic and metagenomic data. In this study, we added two more useful functions to calculate module abundance and Q-value, which indicate the functional abundance and statistical significance of the MCR results, respectively, to the new version of MAPLE for more detailed comparative genomic and metagenomic analyses. Consequently, MAPLE version 2.1.0 reported significant differences in the potential functionome, functional abundance, and diversity of contributors to each function among four metagenomic datasets generated by the global ocean sampling expedition, one of the most popular environmental samples to use with this system. MAPLE version 2.1.0 is now available through the web interface (http://www.genome.jp/tools/maple/) 17 June 2016, date last accessed. PMID- 27374612 TI - Comprehensive analysis of microRNA-Seq and target mRNAs of rice sheath blight pathogen provides new insights into pathogenic regulatory mechanisms. AB - MicroRNAs (miRNAs) are ~22 nucleotide non-coding RNAs that regulate gene expression by targeting mRNAs for degradation or inhibiting protein translation. To investigate whether miRNAs regulate the pathogenesis in necrotrophic fungus Rhizoctonia solani AG1 IA, which causes significant yield loss in main economically important crops, and to determine the regulatory mechanism occurring during pathogenesis, we constructed hyphal small RNA libraries from six different infection periods of the rice leaf. Through sequencing and analysis, 177 miRNA like small RNAs (milRNAs) were identified, including 15 candidate pathogenic novel milRNAs predicted by functional annotations of their target mRNAs and expression patterns of milRNAs and mRNAs during infection. Reverse transcription quantitative polymerase chain reaction results for randomly selected milRNAs demonstrated that our novel comprehensive predictions had a high level of accuracy. In our predicted pathogenic protein-protein interaction network of R. solani, we added the related regulatory milRNAs of these core coding genes into the network, and could understand the relationships among these regulatory factors more clearly at the systems level. Furthermore, the putative pathogenic Rhi-milR-16, which negatively regulates target gene expression, was experimentally validated to have regulatory functions by a dual-luciferase reporter assay. Additionally, 23 candidate rice miRNAs that may involve in plant immunity against R. solani were discovered. This first study on novel pathogenic milRNAs of R. solani AG1 IA and the recognition of target genes involved in pathogenicity, as well as rice miRNAs, participated in defence against R. solani could provide new insights into revealing the pathogenic mechanisms of the severe rice sheath blight disease. PMID- 27374613 TI - Correlation between genome reduction and bacterial growth. AB - Genome reduction by removing dispensable genomic sequences in bacteria is commonly used in both fundamental and applied studies to determine the minimal genetic requirements for a living system or to develop highly efficient bioreactors. Nevertheless, whether and how the accumulative loss of dispensable genomic sequences disturbs bacterial growth remains unclear. To investigate the relationship between genome reduction and growth, a series of Escherichia coli strains carrying genomes reduced in a stepwise manner were used. Intensive growth analyses revealed that the accumulation of multiple genomic deletions caused decreases in the exponential growth rate and the saturated cell density in a deletion-length-dependent manner as well as gradual changes in the patterns of growth dynamics, regardless of the growth media. Accordingly, a perspective growth model linking genome evolution to genome engineering was proposed. This study provides the first demonstration of a quantitative connection between genomic sequence and bacterial growth, indicating that growth rate is potentially associated with dispensable genomic sequences. PMID- 27374614 TI - Z-DNA-forming sites identified by ChIP-Seq are associated with actively transcribed regions in the human genome. AB - Z-DNA, a left-handed double helical DNA is structurally different from the most abundant B-DNA. Z-DNA has been known to play a significant role in transcription and genome stability but the biological meaning and positions of Z-DNA-forming sites (ZFSs) in the human genome has not been fully explored. To obtain genome wide map of ZFSs, Zaa with two Z-DNA-binding domains was used for ChIP-Seq analysis. A total of 391 ZFSs were found and their functions were examined in vivo A large portion of ZFSs was enriched in the promoter regions and contain sequences with high potential to form Z-DNA. Genes containing ZFSs were occupied by RNA polymerase II at the promoters and showed high levels of expression. Moreover, ZFSs were significantly related to active histone marks such as H3K4me3 and H3K9ac. The association of Z-DNA with active transcription was confirmed by the reporter assay system. Overall, our results suggest that Z-DNA formation depends on chromatin structure as well as sequence composition, and is associated with active transcription in human cells. The global information about ZFSs positioning will provide a useful resource for further understanding of DNA structure-dependent transcriptional regulation. PMID- 27374616 TI - Evaluation of anthelmintic activity of biologically synthesized silver nanoparticles against the gastrointestinal nematode, Haemonchus contortus. AB - The present study focuses on the in vitro anthelmintic activity of silver nanoparticles (AgNPs) synthesized using the aqueous extract of Azadirachta indica against Haemonchus contortus. The synthesized AgNPs were characterized by ultraviolet-visible (UV-Vis) spectrophotometry, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD) studies. The UV-Vis spectrum exhibited a sharp peak at 420 nm, which was validated by electron microscopy, indicating the preparation of spherical nanoparticles measuring 15-25 nm in size. The in vitro study was based on an egg hatch assay (EHA) and adult motility inhibition assays. Six concentrations of AgNPs were used for EHA, ranging from 0.00001 to 1.0 MUg/ml, and a range of 1-25 MUg/ml was used for adult worms. The highest concentration induced 85 +/- 2.89% egg hatch inhibition. The IC50 value for EHA was 0.001 MUg/ml, whereas in vitro adult H. contortus motility inhibition was produced at 7.89 MUg/ml (LC50). The effectiveness of A. indica leaf extract (aqueous) was also evaluated, which showed an IC50 value for EHA of 115.67 MUg/ml, while the LC50 against adult H. contortus was 588.54 MUg/ml. The overall findings of the present study show that the experimental plant extract contains reducing properties for the synthesis of AgNPs which, in turn, showed potent anthelmintic properties. This is the first report where AgNPs have been tested for their anthelmintic properties in an in vitro model. PMID- 27374615 TI - The draft genome of MD-2 pineapple using hybrid error correction of long reads. AB - The introduction of the elite pineapple variety, MD-2, has caused a significant market shift in the pineapple industry. Better productivity, overall increased in fruit quality and taste, resilience to chilled storage and resistance to internal browning are among the key advantages of the MD-2 as compared with its previous predecessor, the Smooth Cayenne. Here, we present the genome sequence of the MD-2 pineapple (Ananas comosus (L.) Merr.) by using the hybrid sequencing technology from two highly reputable platforms, i.e. the PacBio long sequencing reads and the accurate Illumina short reads. Our draft genome achieved 99.6% genome coverage with 27,017 predicted protein-coding genes while 45.21% of the genome was identified as repetitive elements. Furthermore, differential expression of ripening RNASeq library of pineapple fruits revealed ethylene-related transcripts, believed to be involved in regulating the process of non-climacteric pineapple fruit ripening. The MD-2 pineapple draft genome serves as an example of how a complex heterozygous genome is amenable to whole genome sequencing by using a hybrid technology that is both economical and accurate. The genome will make genomic applications more feasible as a medium to understand complex biological processes specific to pineapple. PMID- 27374618 TI - Sulfitobacter faviae sp. nov., isolated from the coral Faviaveroni. AB - Three closely related, non-sporulating, aerobic, Gram-stain-negative, motile, rod shaped isolates (S5-53T, S6-62 and S6-64) were obtained from mucus of corals Favia veroni from the Andaman Sea, India. Colonies grown on marine agar were small, circular and cream-coloured. Heterotrophic growth was observed at 10-40 degrees C and pH 6-10; optimum growth occurred at 25-30 degrees C and pH 7-8. 16S rRNA gene sequence analysis confirmed the isolates belonged to the genus Sulfitobacter and the three isolates shared more than 99 % pairwise sequence similarity. Strain S5-53T shared highest 16S rRNA gene sequence similarity of 98.43 % with Sulfitobacter dubius KMM 3554T. DNA-DNA relatedness among the three isolates was above 70 % whereas strain S5-53T showed less than 70 % relatedness with the type strains of closely related species. The DNA G+C content of strain S5-53T was 61 mol%. It contained phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and diphosphatidylglycerol as major polar lipids. Predominant fatty acids included C18 : 1omega7c, C18 : 1omega7c 11-methyl, C16 : 0 and C10 : 0 3-OH. Q10 was the major respiratory quinone. Based on this polyphasic analysis, the new isolates (S5-53T, S6-62 and S6-64) are considered to represent a novel species of the genus Sulfitobacter, for which the name Sulfitobacter faviae sp. nov. is proposed. The type strain is S5-53T(=JCM 31093T=LMG 29156T). PMID- 27374619 TI - Topical and Targeted Delivery of siRNAs to Melanoma Cells Using a Fusion Peptide Carrier. AB - Topical application of siRNAs through the skin is a potentially effective strategy for the treatment of melanoma tumors. In this study, we designed a new and safe fusion peptide carrier SPACE-EGF to improve the skin and cell penetration function of the siRNAs and their targeting ability to B16 cells, such that the apoptosis of B16 cells can be induced. The results show that the carrier is stable and less toxic. The EGF motif does not affect the skin and cell penetration function of the SPACE. Because EGF can strongly bind EGFR, which is overexpressed in cancer cells, the targeting ability of the SPACE-EGF-siRNA complex is increased. In vitro experiments indicate that GAPDH siRNAs conjugated with SPACE-EGF can significantly reduce the GAPDH concentration in B16 cells, and c-Myc siRNAs can cause the gene silencing of c-Myc and thus the apoptosis of cells. In vivo experiments show that the topical application of c-Myc siRNAs delivered by SPACE-EGF through the skin can significantly inhibit the growth of melanoma tumors. This work may provide insight into the development of new transdermal drug carriers to treat a variety of skin disorders. PMID- 27374620 TI - Changes in Caregiver Knowledge and Perceived Competency Following Group Education about Sensory Processing Disturbances: An Exploratory Study. AB - Parents or teachers (n = 10) of children diagnosed on the autism spectrum and exhibiting sensory processing disorders (SPD) attended a series of six weekly educational sessions designed to increase the participants' knowledge of SPD, skills in interacting with children exhibiting SPD and confidence in intervening with children exhibiting undesirable behaviours stemming from SPD. The sessions consisted of group classroom instruction with instructional methods including PowerPoint-assisted lecture/discussion and short video clips. Pre-test and post test assessment was made of the participants' (a) self-perceived knowledge of sensory processing concepts; (b) actual knowledge of sensory processing concepts; and (c) self-rated competency for dealing with children exhibiting behaviours related to SPD. Statistical analysis revealed significant gains were achieved on all measures. The results were interpreted as indicating that group classroom instruction is an effective means of increasing such caregivers' self-perceived knowledge of sensory processing concepts, actual knowledge of sensory processing concepts and self-rated competency for dealing with children exhibiting behaviours related to SPD. Future research to assess the short-term and long-term impacts of these gains and to gauge the relative effectiveness of various contents for such sessions is recommended. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27374621 TI - Pneumothorax in cystic fibrosis: beyond the guidelines. AB - Pneumothorax is a serious but common complication in patients with cystic fibrosis (CF). It has adverse prognostic implications as well as associations with subsequent reduction in lung function and significant risk of recurrence. Management dilemmas frequently occur that are beyond current guidelines. We review the evidence and highlight management difficulties in pneumothoraces in CF. PMID- 27374622 TI - Severe Achromobacter xylosoxidans infection and loss of sputum bacterial diversity in an adult patient with cystic fibrosis. AB - Achromobacter spp. are emerging pathogens in the lungs of patients with cystic fibrosis. We report the case of an adult patient with cystic fibrosis and chronic A. xylosoxidans infection who experienced rapid, progressive clinical deterioration. Metagenomic analysis of the sputum revealed that the airway microbiota was almost entirely dominated by A. xylosoxidans. We review the impact of this organism on lung function and the airway microbiome in cystic fibrosis, and discuss the potential for cross-infection between patients. PMID- 27374623 TI - Phthalates in neonatal health: friend or foe? AB - Exposure to environmental chemicals has adverse effects on the health and survival of humans. Emerging evidence supports the idea that exposure to endocrine-disrupting compounds (EDCs) can perturb an individual's physiological set point and as a result increase his/her propensity toward several diseases. The purpose of this review is to provide an update on di-(2-ethylhexyl) phthalate, the primary plasticizer found in plastic medical devices used in neonatal intensive care units, its effects on the fetus and newborn, epidemiological studies, pharmacokinetics, toxicity and epigenetic implications. We searched the PubMed databases to identify relevant studies. Phthalates are known EDCs that primarily are used to improve the flexibility of polyvinyl chloride plastic products and are called plasticizers in lay terms. Neonates and infants are particularly vulnerable to the effects of phthalates, beginning with maternal exposure and placental transfer during gestation and during infancy following birth. In line with the developmental origins of adult disease, a focus on the effects of environmental chemicals in utero or early childhood on the genesis of adult diseases through epigenome modulation is timely and important. The epigenetic effects of phthalates have not been fully elucidated, but accumulating evidence suggests that they may be associated with adverse health effects, some of which may be heritable. Phthalate exposure during pregnancy and the perinatal period is particularly worrisome in health-care settings. Although the clinical significance of phthalate exposure has been difficult to assess with epidemiologic studies, the evidence that physiological changes occur due to exposure to phthalates is growing and points toward the need for more investigation at a molecular, specifically epigenetic level. PMID- 27374624 TI - Time-course metabolic changes in high-fat diet-induced obesity rats: A pilot study using hyperpolarized (13)C dynamic MRS. AB - The purpose of this study was to investigate the time-course metabolic changes based on hyperpolarized (13)C magnetic resonance spectroscopy (MRS) in high-fat diet (HFD)-induced obesity rats and the correlation between metabolic and serum enzyme levels. Sprague-Dawley rats were fed either HFD (60% fat) or normal diet (10% fat) for 6weeks. A HyperSense DNP was used to hyperpolarize [1-(13)C] pyruvic acid and the hyperpolarized (13)C MRS was examined every 2weeks in the course of 6weeks using a 3T GE MR750 scanner. The body weight of HFD-induced obese rats was significantly increased compared to normal rats at the 6th week after the onset of feeding (p=0.05). Simultaneously, the HFD-induced obese rats showed significantly increased levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and low-density lipoprotein (LDL)-cholesterol compared to normal rats (p<=0.05). In the dynamic (13)C MR spectra acquired at the 6th week, the obese rats showed significantly increased ratios of [1-(13)C] lactate/[1-(13)C] pyruvate and [1-(13)C] alanine/[1 (13)C] pyruvate (p=0.05). The (13)C spectral outcomes are positively correlated with the enzyme levels of ALT and LDH in the HFD-induced obesity. The [1-(13)C] lactate and [1-(13)C] alanine are potentially considered as noninvasive biomarkers for the HFD-induced obesity. PMID- 27374625 TI - Mucosal expression of DEC-205 targeted allergen alleviates an asthmatic phenotype in mice. AB - Considering the rising incidence of allergic asthma, the symptomatic treatments that are currently applied in most cases are less than ideal. Specific immunotherapy is currently the only treatment that is able to change the course of the disease, but suffers from a long treatment duration. A gene based immunization that elicits the targeting of allergens towards dendritic cells in a steady-state environment might have the potential to amend these difficulties. Here we used a replication deficient adenovirus to induce the mucosal expression of OVA coupled to a single-chain antibody against DEC-205. A single intranasal vaccination was sufficient to mitigate an OVA-dependent asthmatic phenotype in a murine model. Invasive airway measurements demonstrated improved lung function after Ad-Dec-OVA treatment, which was in line with a marked reduction of goblet cell hyperplasia and lung eosinophilia. Furthermore OVA-specific IgE titers and production of type 2 cytokines were significantly reduced. Together, the here presented data demonstrate the feasibility of mucosal expression of DEC-targeted allergens as a treatment of allergic asthma. PMID- 27374626 TI - Importance of air bubbles in the core of coated pellets: Synchrotron X-ray microtomography allows for new insights. AB - High-resolution X-ray microtomography was used to get deeper insight into the underlying mass transport mechanisms controlling drug release from coated pellets. Sugar starter cores were layered with propranolol HCl and subsequently coated with Kollicoat SR, plasticized with 10% TEC. Importantly, synchrotron X ray computed microtomography (SR-MUCT) allowed direct, non-invasive monitoring of crack formation in the film coatings upon exposure to the release medium. Propranolol HCl, as well as very small sugar particles from the pellets' core, were expulsed through these cracks into the surrounding bulk fluid. Interestingly, SR-MUCT also revealed the existence of numerous tiny, air-filled pores (varying in size and shape) in the pellet cores before exposure to the release medium. Upon water penetration into the system, the contents of the pellet cores became semi-solid/liquid. Consequently, the air-pockets became mobile and fused together. They steadily increased in size (and decreased in number). Importantly, "big" air bubbles were often located in close vicinity of a crack within the film coating. Thus, they play a potentially crucial role for the control of drug release from coated pellets. PMID- 27374627 TI - Development of biodegradable hyperbranched core-multishell nanocarriers for efficient topical drug delivery. AB - The topical application of drugs allows for a local application in skin disease and can reduce side effects. Here we present biodegradable core-multishell (CMS) nanocarriers which are composed of a hyperbranched polyglycerol core functionalized with diblock copolymers consisting of polycaprolactone (PCL) and poly(ethylene glycol) (mPEG) as the outer shell. The anti-inflammatory drug Dexamethasone (Dexa) was loaded into these CMS nanocarriers. DLS results suggested that Dexa loaded nanoparticles mostly act as a unimolecular carrier system. With longer PCL segments, a better transport capacity is observed. In vitro skin permeation studies showed that CMS nanocarriers could improve the Nile red penetration through the skin by up to 7 times, compared to a conventional cream formulation. Interestingly, covalently FITC-labeled CMS nanocarriers remain in the stratum corneum layer. This suggests the enhancement is due to the release of cargo after being transported into the stratum corneum by the CMS nanocarriers. In addition, the hPG-PCL-mPEG CMS nanocarriers exhibited good stability, low cytotoxicity, and their production can easily be scaled up, which makes them promising nanocarriers for topical drug delivery. PMID- 27374628 TI - The effect of linker type and recognition peptide conjugation chemistry on tissue affinity and cytotoxicity of charged polyacrylamide. AB - To increase colonoscopy competence in ambiguous situations (e.g. the existence of flat polyps), an explicit in situ (at real time) diagnosis at the molecular level is required. We have previously shown that the affinity of fluorescent cationic polyacrylamide (Flu-CPAA) to malignant regions in the colon mucosa can be improved by conjugating the recognition peptide EPPT1 to the polymer backbone (to form Flu-CPAA-Pep). Using another recognition peptide, namely VRPMPLQ, we elucidated in the present study the effect of linker type and conjugating methods on Flu-CPAA-VRPMPLQ cytotoxicity and on its affinity to cell lines as well as human colorectal cancer (CRC) biopsies. In order to derive the relationship between the response variable and the experimental factors in a minimal set of experiments, a computerized statistical design of experiment (DoE) strategy was implemented. Data were collected in a six-factor factorial design to study the effect of experimental factors (independent variables) on the ability of the Flu CPAA polymers to bind specifically to the colon cancer cell lines or the human biopsies (the response). It was found that the presence of VRPMPLQ on the Flu CPAA improved the polymer's affinity to the human CRC biopsies and to the colon cancer cell lines representing stage B in the Duke severity staging system. The cytotoxicity of Flu-CPAA with high charge density was reduced after conjugated with VRPMPLQ. The replacement of Ahx linker by PEG linker of similar length did not affect the affinity to the human biopsies, nor did it affect cytotoxicity. However, elongating the PEG linker reduced the in vitro affinity to the colon cancer cell lines and to human CRC biopsies. Changing the conjugation method from condensation (amide bond formation) to the click conjugation method did not affect the affinity properties of the polymers. It did reduce, however, the polymer cytotoxicity. We suggest that Flu-CPAA-Pep, with the VRPMPLQ peptide as a recognition moiety, could serve for early diagnosis and screening of CRC patients during endoscopic procedures. PMID- 27374629 TI - Inhibition of the cancer-associated TASK 3 channels by magnetically induced thermal release of Tetrandrine from a polymeric drug carrier. AB - Two-pore domain (K2P) potassium channels have recently attracted growing interest in the field of cancer research. These channels play an important role in cancer biology specifically for cancer progression, including proliferation, migration, and apoptosis, which makes them an attractive target for novel cancer therapies. Here, we examined the effect of Tetrandrine (Tet), a natural compound known as a channel modulator, which is associated with anticancer activities, as potential drug in this regard. Xenopus oocyte with overexpression of K2P 9.1 (TASK 3) channels has been chosen as model system for this purpose. In order to release Tet and trigger the channels we developed a polymeric magnetic delivery system: Tetrandrine-Magnetite co-loaded poly (lactic-co-glycolic) acid particles. The embedded iron oxide magnetite (Fe3O4) nanoparticles (NPs) allow to inductively heat the particles by applying a high frequency alternating magnetic field, and thus trigger the release of the co-encapsulated Tet. As a proof of concept the nanoparticulate drug delivery system was heated by raising the suspension's temperature proving the temperature dependent release behaviour. Both heating approaches were then successfully applied for measuring the TASK 3 channels current in response to the released drug. It was found that the released Tet amount is sufficient to inhibit the TASK 3 channels in a dose dependent manner. Thus, such a stimulus responsive drug delivery system holds great promise as a novel approach for the treatment of various cancer types such as for the interaction with the two-pore domain potassium channels K2P 9.1. PMID- 27374630 TI - In vivo comparative study of distinct polymeric architectures bearing a combination of paclitaxel and doxorubicin at a synergistic ratio. AB - Nowadays, combination therapy became a standard in oncology. In this study, we compare the activity of two polymeric carriers bearing a combination of the anticancer drugs paclitaxel (PTX) and doxorubicin (DOX), which differ mainly in their architecture and supramolecular assembly. Drugs were covalently bound to a linear polymer, polyglutamic acid (PGA) or to a dendritic scaffold, polyglycerol (PG) decorated with poly(ethylene glycol) (PEG), forming PGA-PTX-DOX and PG-PTX bz-DOX-PEG, respectively. We explored the relationship between the polymeric architectures and their performance with the aim to augment the pharmacological benefits of releasing both drugs simultaneously at the tumor site at a synergistic ratio. We recently designed and characterized a PGA-PTX-DOX conjugate. Here, we describe the synthesis and characterization of PG dendritic scaffold bearing the combination of PTX and DOX. The performance of both conjugates was evaluated in a murine model of mammary adenocarcinoma in immunocompetent mice, to investigate whether the activity of the treatments is affected by the immune system. Drug conjugation to a nano-sized polymer enabled preferred tumor accumulation by extravasation-dependent targeting, making use of the enhanced permeability and retention (EPR) effect. Both PGA-PTX-DOX and PG-PTX bz-DOX-PEG nano-sized conjugates exhibited superior anti-tumor efficacy and safety compared to the combination of the free drugs, at equivalent concentrations. However, while PGA-PTX-DOX was more efficient than a mixture of each drug conjugated to a separate PGA chain, as was previously shown, PG-PTX-bz DOX-PEG had similar activity to the mixture of the PG-PTX-bz-PEG and PG-DOX-PEG conjugates. Our results show that both conjugates are potential candidates as precision combination nanomedicines for the treatment of breast cancer. PMID- 27374632 TI - Hierarchical multivariate mixture generalized linear models for the analysis of spatial data: An application to disease mapping. AB - Disease mapping of a single disease has been widely studied in the public health setup. Simultaneous modeling of related diseases can also be a valuable tool both from the epidemiological and from the statistical point of view. In particular, when we have several measurements recorded at each spatial location, we need to consider multivariate models in order to handle the dependence among the multivariate components as well as the spatial dependence between locations. It is then customary to use multivariate spatial models assuming the same distribution through the entire population density. However, in many circumstances, it is a very strong assumption to have the same distribution for all the areas of population density. To overcome this issue, we propose a hierarchical multivariate mixture generalized linear model to simultaneously analyze spatial Normal and non-Normal outcomes. As an application of our proposed approach, esophageal and lung cancer deaths in Minnesota are used to show the outperformance of assuming different distributions for different counties of Minnesota rather than assuming a single distribution for the population density. Performance of the proposed approach is also evaluated through a simulation study. PMID- 27374631 TI - Injectable alginate hydrogel for enhanced spatiotemporal control of lentivector delivery in murine skeletal muscle. AB - Hydrogels are an especially appealing class of biomaterials for gene delivery vehicles as they can be introduced into the body with minimally invasive procedures and are often applied in tissue engineering and regenerative medicine strategies. In this study, we show for the first time the use of an injectable alginate hydrogel for controlled delivery of lentivectors in the skeletal muscle of murine hindlimb. We propose to alter the release rates of lentivectors through manipulation of the molecular weight distribution of alginate hydrogels. The release of lentivector was tested using two different ratios of low and high molecular weight (MW) alginate polymers (75/25 and 25/75 low/high MW). The interdependency of lentivector release rate and alginate degradation rate was assessed in vitro. Lentivector-loaded hydrogels maintained transduction potential for up to one week in vitro as demonstrated by the continual transduction of HEK 293T cells. Injection of lentivector-loaded hydrogel in vivo led to a sustained level of transgene expression for more than two months while minimizing the copies of lentivirus genome inserted into the genome of murine skeletal muscle cells. This strategy of spatiotemporal control of lentivector delivery from alginate hydrogels may provide a versatile tool to combine gene therapy and biomaterials for applications in regenerative medicine. PMID- 27374633 TI - Emerging hydrogel designs for controlled protein delivery. AB - Hydrogels have evolved into indispensable biomaterials in the fields of drug delivery and regenerative medicine. This minireview aims to highlight the recent advances in the hydrogel design for controlled release of bioactive proteins. The latest developments of enzyme-responsive and externally regulated drug delivery systems are summarized. The design strategies and applications of phase-separated hydrogel systems are also described. We expect that these emerging approaches will enable expanded use of hydrogels in biomedicine and healthcare. PMID- 27374634 TI - Subcutaneous fat necrosis due to molecular-targeted therapy. PMID- 27374635 TI - Closure of aortopulmonary window using Nit-Occlud(r) PDA-R device in a 3-month old infant. AB - Aortopulmonary window (APW) is a rare abnormality in which a pulmonary defect exists between the ascending aorta and the main pulmonary artery. Given that it may result in cardiac failure and pulmonary vascular disease in the early period, treatment needs to be performed without delay. In addition to surgical treatment, transcatheter closure may also be performed for selected patients. This study describes the case of an infant diagnosed with APW and who underwent successful transcatheter closure using a Nit-Occlud(r) PDA-R device. PMID- 27374636 TI - Combinatorial antibody libraries: new advances, new immunological insights. AB - Immunochemists have become quite proficient in engineering existing antibody molecules to control their pharmacological properties. However, in terms of generating new antibodies, the combinatorial antibody library has become a central feature of modern immunochemistry. These libraries are essentially an immune system in a test tube and enable the selection of antibodies without the constraints of whole animal or cell-based systems. This Review provides an overview of how antibody libraries are constructed and discusses what can be learnt from these synthetic systems. In particular, the Review focuses on new biological insights from antibody libraries - such as the concept of 'SOS antibodies' - and the growing use of intracellular antibodies to perturb cellular functions. PMID- 27374638 TI - Macrophages: Memories of the dead give strength. PMID- 27374639 TI - Femoral Component Rotation in Total Knee Arthroplasty: A Comparison Between Transepicondylar Axis and Posterior Condylar Line Referencing. AB - BACKGROUND: Proper rotational alignment of the femoral component is critical for a successful total knee arthroplasty (TKA). Controversy remains regarding the optimal intraoperative reference to determine femoral component rotation. METHODS: Thirty-one patients who underwent magnetic resonance imaging of a TKA between April 2008 and November 2015 were retrospectively reviewed. A single surgeon performed the TKA using a posterior condylar angle of 3 degrees (PCA group) or surgical transepicondylar axis (TEA group) to determine femoral component rotation. The hip-knee-ankle angle and the tibial plateau-tibial shaft angle (TPTSA) were measured on full-length x-rays, and the rotation of the femoral component was measured as compared to the TEA on magnetic resonance imaging (negative values indicate internal rotation). RESULTS: The median measured rotational deviation of the femoral component from the TEA was significantly higher in the PCA group than in the TEA group (-3.8 +/- 2.9 degrees and -1.4 +/- 1.9 degrees , respectively) (P = .02). When knees with preoperative varus and neutral alignment were evaluated, the median measured rotational deviation of the femoral component was significantly higher in the fixed PCL group than in the TEA group (-3.4 +/- 3.3 degrees and -0.61 +/- 1.3 degrees , respectively) (P = .04). Linear regression used to evaluate the relationship between the TPTSA and femoral component rotational deviation from the TEA revealed similar near zero slopes (P = .90); however, the Y intercepts in the TEA group were significantly higher than the PCA group (-2.8 +/- 0.7 and -5.5 +/- 1.1, respectively) (P = .007). CONCLUSION: The use of the surgical TEA as an intraoperative rotational reference is more reliable than the PCA in valgus, varus, and neutrally aligned knees independent from the magnitude of the TPTSA. PMID- 27374640 TI - BaeR protein acts as an activator of nuclear factor-kappa B and Janus kinase 2 to induce inflammation in murine cell lines. AB - BaeR, a response regulator protein, takes part in multidrug efflux, bacterial virulence activity, and other biological functions. Recently, BaeR was shown to induce inflammatory responses by activating the mitogen-activated protein kinases (MAPKs). In this study, we investigated additional pathways used by BaeR to induce an inflammatory response. BaeR protein was purified from Salmonella enterica Paratyphi A and subcloned into a pPosKJ expression vector. RAW 264.7 cells were treated with BaeR, and RNA was extracted by TRIzol reagent for RT-PCR. Cytokine gene expression was analyzed by using the comparative cycle threshold method, while western blotting and ELISA were used to assess protein expression. We confirmed that BaeR activates nuclear factor-kappa B (NF-kappaB), thereby inducing an inflammatory response and increases the production of interleukins (IL-)1beta and IL-6. During this process, the Janus kinase 2 (JAK2)-STAT1 signaling pathway was activated, resulting in an increase in the release of interferons I and II. Additionally, COX-2 was activated and its expression increased with time. In conclusion, BaeR induced an inflammatory response through activation of NF-kappaB in addition to the MAPKs. Furthermore, activation of the JAK2-STAT1 pathway and COX-2 facilitated the cytokine binding activity, suggesting an additional role for BaeR in the modulation of the immune system of the host and the virulence activity of the pathogen. PMID- 27374637 TI - Immune responses and immunopathology in acute and chronic viral hepatitis. AB - Hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) are responsible for most cases of viral hepatitis. Infection by each type of virus results in a different typical natural disease course and clinical outcome that are determined by virological and immunological factors. HCV tends to establish a chronic persistent infection, whereas HAV does not. HBV is effectively controlled in adults, although it persists for a lifetime after neonatal infection. In this Review, we discuss the similarities and differences in immune responses to and immunopathogenesis of HAV, HBV and HCV infections, which may explain the distinct courses and outcomes of each hepatitis virus infection. PMID- 27374664 TI - IgE-binding potencies of three peach Pru p 1 isoforms. AB - SCOPE: Pru p 1, the Bet v 1 homologue from peach, has been identified as a clinically relevant allergen. Three isoforms have been described, two in peach fruit (Pru p 1.0101 and Pru p 1.0201) and one in pollen (Pru p 1.0301). The present study aimed to compare their IgE-binding potencies. METHODS AND RESULTS: Three Pru p 1 isoforms were cloned and expressed as soluble proteins with His tags in Escherichia coli. Protein identity was confirmed by MS, circular dichroism, and RNAse activity. IgE-binding capacity using ELISA and ImmunoCAP was compared. Three Pru p 1 isoforms had quite similar IgE-binding potencies for 60% of the sera, but more than twofold between any two isoforms among 40% of the 47 sera. The mean IgE binding of Pru p 1.0201 was slightly higher than other two isoforms. In a sera pool, homologous ImmunoCAP inhibition was higher than other two heterologous isoforms. Individual serum with diverse IgE values of three isoforms demonstrated the higher IgE inhibition of specific isoform with higher IgE value. CONCLUSION: A similar and variable pattern of IgE recognition was observed among three Pru p 1 isoforms. The two new isoforms can be used as more accurate diagnostic reagents. PMID- 27374665 TI - A Dilemma on Re-biopsy in the Era of Precision Cancer Therapy. PMID- 27374666 TI - Prevalence of Simple Renal Cysts in Acromegaly. AB - Objective Various organs are known to be affected by the comorbidities of acromegaly. However, the involvement of renal structural comorbidities, such as cysts, has so far remained largely unknown. In this single-center study, we aimed to determine the prevalence and factors associated with simple renal cysts in Japanese patients with acromegaly. Methods A total of 71 consecutive patients with acromegaly were analyzed, who all underwent abdominal ultrasonography at diagnosis between 1986 and 2012 at Kobe University Hospital. Results Of these 71 patients, 23 (32.4%) exhibited simple renal cysts. Acromegalic patients with renal cysts tended to be significantly older, had a higher prevalence of smoking- and higher nadir growth hormone (GH) levels during the oral glucose tolerance test (OGTT) than did those without renal cysts. A multivariate logistic regression analysis showed age, smoking, and nadir GH to be independent factors associated with renal cysts. Interestingly, the number of renal cysts positively correlated with both the basal GH levels and nadir GH levels during OGTT (r=0.66, p<0.05 and r=0.70, p<0.05, respectively). In addition, the mean diameter of renal cysts positively correlated with the systolic blood pressure (r=0.84, p<0.005). Conclusion This is the first report to show the prevalence of simple renal cysts in patients with acromegaly. Elevated nadir GH levels during OGTT were found to be associated with an increased risk of simple renal cysts. Therefore, an excessive secretion of GH may be related to the development of renal cysts. PMID- 27374667 TI - Impact of the Visceral Fat Area Measured by Dual Impedance Method on the Diagnostic Components of Metabolic Diseases in a Middle-aged Japanese Population. AB - Objective The aim of this study was to examine the associations between the visceral fat area (VFA) and the subcutaneous fat area (SFA) as estimated by the dual impedance method with a body composition monitor (BCM) and the diagnostic components of metabolic syndrome in a middle-aged Japanese population. Methods The subjects included 303 men (average age 51.3+/-9.0 years old) and 345 women (average age 40.0+/-9.4 years old). The VFA and SFA were estimated by BCM, and the associations among the components of metabolic syndrome (waist circumference, blood pressure and related blood sample tests) were evaluated. Results VFA showed positive correlations with waist circumference, HbA1c, high-density lipoprotein (HDL)/low-density lipoprotein (LDL) cholesterol, triglyceride and uric acid level in men, while showing positive correlations with waist circumference, HDL cholesterol, triglyceride and HbA1c in women. The estimated SFA showed positive correlations with systolic blood pressure, HDL/LDL cholesterol and triglyceride in men, and HDL cholesterol and triglyceride in women. A receiver operating characteristic (ROC) analysis showed the estimated VFA to be as effective as WC to identify subject with metabolic syndrome. Conclusion By estimating the VFA using BCM, it may be possible to identify patients at risk of developing metabolic syndrome and hyperuricemia. PMID- 27374668 TI - Effect of Switching from Sulphonylurea to Repaglinide Twice or Three Times Daily for 4 Months on Glycemic Control in Japanese Patients with Type 2 Diabetes. AB - Objective Switching from sulfonylureas to repaglinide in patients with type 2 diabetes improves glycemic control; however, the optimal dosage has not been fully evaluated. We designed to show that repaglinide was equivalent to sulfonylurea in Japanese patients with type 2 diabetes. We herein evaluated whether we could switch from sulfonylureas to repaglinide twice or thrice daily in Japanese adult patients who had been treated with anti-diabetic drugs, including sulfonylureas, and whose conditions were moderately well-controlled. Methods A total of 78 patients taking less than half the Japanese maximum dose of sulfonylurea were randomized into three groups: 26 in group A (switching from sulfonylureas to taking 0.25 or 0.5 mg of repaglinide just before breakfast and dinner twice daily), 27 in group B (switching from sulfonylureas to taking 0.25 or 0.5 mg of repaglinide just before meals thrice daily), and 25 in group C (continuing to take sulfonylurea). Blood samples were collected at 0, 1, 2, 3, and 4 months following the initiation of the maintenance period. Results The HbA1c and glycoalbumin levels did not significantly differ among the three groups after 4 months of treatment. Conclusion With the assumption that 1 mg of glimepiride is equivalent to 1.25 mg of glibenclamide or 40 mg of gliclazide, the administration of repaglinide (0.44 mg/meal) twice and thrice daily is similar to the efficacy of sulfonylurea (glimepiride 1.63-1.98 mg/day) after four months of treatment in Japanese patients with moderately well-controlled type 2 diabetes (HbA1c, 7-7.5%). PMID- 27374669 TI - Factors Affecting the Diagnostic Yield of Transbronchial Biopsy Using Endobronchial Ultrasonography with a Guide Sheath in Peripheral Lung Cancer. AB - Objective Endobronchial ultrasonography with a guide sheath (EBUS-GS) and virtual bronchoscopic navigation (VBN) improves the diagnostic yield in patients with peripheral pulmonary lesions (PPLs). Most previous reports on EBUS-GS-guided transbronchial biopsy (TBB) have included patients with benign and malignant diseases. We aimed to determine the factors that predicted a successful diagnosis by EBUS-GS-guided TBB diagnostic in patients with small peripheral lung cancer, with a focus on the high-resolution computed tomography (HRCT) findings before bronchoscopy. Methods We retrospectively reviewed the medical records of 173 consecutive patients with 175 small (<=30 mm) PPLs who were diagnosed with primary lung cancer between June 2010 and October 2013 at Nagoya University Hospital. All patients underwent EBUS-GS-guided TBB with VBN using a ZioStation computer workstation (Ziosoft, Osaka, Japan). We analyzed the patient characteristics, HRCT findings, diagnostic yield, and the diagnostic factors in small peripheral lung carcinoma. Results The EBUS probe position was within the PPL in 83 of the 175 lesions (47%) and 112 (64.0%) cases were successfully diagnosed by EBUS-GS-guided TBB. A univariate analysis revealed that the following factors were associated with a significantly higher diagnostic yield: CT bronchus sign positivity, a lesion of >20 mm in diameter, a solid nodule, and a probe position that was within the lesion. The following factors were not significant: the lesion location, the number of biopsies, and the lung cancer histology. A multivariate analysis revealed that the following factors significantly affected the diagnostic yield: CT bronchus sign positivity [odds ratio (OR) =2.479]; a probe position that was within the lesion (OR=2.542); and a solid nodule (OR=2.304). Conclusion The significant factors that were significantly associated with a successful diagnosis using EBUS-GS-guided TBB in small peripheral lung carcinoma were as follows: CT bronchus sign positivity, a solid nodule, and a probe position that was within the lesion. PMID- 27374670 TI - Atypical Pleural Fluid Profiles in Tuberculous Pleural Effusion: Sequential Changes Compared with Parapneumonic and Malignant Pleural Effusions. AB - Objective Although tuberculous pleural effusion (TPE) is commonly characterized by lymphocytic predominance and high adenosine deaminase (ADA) levels, it may present with neutrophilic predominance or low ADA levels, which are more commonly found in parapneumonic effusion (PPE) or malignant pleural effusion (MPE), respectively. A few studies have observed that the atypical pleural fluid profiles of these cases of TPE may resolve at follow-up thoracentesis. However, these observations were incompletely analyzed and lacked comparison with proper control groups. Thus, limited data are available comparing the sequential pleural fluid changes between TPE and PPE or MPE with similar pleural fluid profiles. Methods TPE, PPE, and MPE patients who underwent sequential thoracentesis were retrospectively reviewed. The sequential changes in the pleural fluid profiles were compared between neutrophilic TPE and PPE, and lymphocytic TPE and MPE with low ADA levels. Results Twenty-three TPE patients (16 with neutrophilic exudates, seven with lymphocytic exudates), 72 cases of PPE with neutrophilic exudates, and 18 cases of MPE with lymphocytic exudates were included in the analysis. A sequential shift to lymphocytic exudates occurred significantly more often in TPE than in PPE cases. The initial and follow-up ADA levels in TPE cases with a lymphocytic shift were significantly higher than those in PPE cases with a lymphocytic shift. The ADA levels in the TPE cases with initial lymphocytic exudates and low ADA levels significantly increased at follow-up thoracentesis. For the TPE and MPE cases with initial lymphocytic exudates and ADA levels <40 U/L, the frequency of effusion with ADA levels >=40 U/L at the second thoracentesis was significantly higher in the TPE cases. Conclusion Follow-up thoracentesis may provide useful information for clinical decision-making in suspected atypical TPE cases with neutrophilic exudates or low ADA levels. PMID- 27374671 TI - Allogeneic Hematopoietic Stem Cell Transplantation after Conditioning Regimens with Fludarabine/melphalan or Fludarabine/busulfan for Patients with Hematological Malignancies: A Single-center Analysis. AB - Objective Fludarabine plus melphalan (FM) and fludarabine plus busulfan (FB) are two major conditioning regimens for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods We retrospectively analyzed patients who underwent allo-HSCT after a conditioning regimen consisting of FM or FB with/without total body irradiation for hematological malignancies between 2005 and 2014. Results There were 41 patients who met the criteria. The median follow up time for the survivors was 3 years. Thirty-two patients received allo-HSCT after the FM regimen and nine patients received allo-HSCT after the FB regimen. Patients who received FB were older than those who received FM (p=0.041). There was no significant difference in the 3-year overall survival between patients who had received FB and those who had received FM (29.6% vs. 56.5%, p=0.267). The 3 year cumulative incidence of relapse was significantly higher in patients who had received FB than that in patients who had received FM (66.7% vs. 17.8%, p=0.004), and FB was an independent prognostic factor for relapse by a multivariate analysis (hazard ratio, 9.8; 95% confidential interval, 2.5-39.3; p=0.001). When we restricted the evaluation to patients with acute myeloid leukemia and myelodysplastic syndrome, the 3-year cumulative incidence of relapse was also significantly higher in patients who had received FB than that in patients who had received FM (75.0% vs. 16.1%, p=0.004). Conclusion The results suggest that FM may provide better disease control than FB. PMID- 27374672 TI - Association of Hay Fever with the Failure of Helicobacter pylori Primary Eradication. AB - Objective Recently, the number of patients receiving Helicobacter pylori eradication treatment has dramatically increased in Japan, although the eradication rate has gradually decreased. Patient characteristics could affect the eradication rate. Our aim in this study was to investigate the association between failed first-line eradication therapy and hay fever. Methods We researched 356 patients who visited a pharmacy adjacent to the Internal Medicine clinic with a prescription for first-line H. pylori eradication treatment and investigated whether the patients had hay fever using a questionnaire. We separated these patients into 2 groups based on the success or failure of eradication according to the clinical data and performed a logistic regression analysis to investigate the influence of hay fever on first-line eradication failure. Results The eradication rate of patients with and without hay fever was 65.6% and 77.7%, respectively. The adjusted odds ratios according to which patients with hay fever would fail eradication therapy gradually lowered with increasing patient age [<=50 years, odds ratio (OR) 6.81, p=0.089; 51-60 years, OR 2.75, p=0.145; 61-70 years, OR 1.60, p=0.391; >70 years, OR 1.02, p=0.979]. A significant relationship was found for all patients (OR 1.88, p=0.047) and the age group <=70 years (OR 2.31, p=0.024). Conclusion Patients with hay fever have difficulty with first-line eradication, especially younger patients. The existence of clarithromycin-resistant bacteria is suspected, and other factors may also be involved. When a hay fever sufferer receives first-line treatment, eradication might be difficult and other treatment may be required. PMID- 27374673 TI - Improvements in Pneumatosis Cystoides Intestinalis and Hepatic Portal Venous Gas with Conservative Therapy in a Patient on Maintenance Dialysis. AB - A 77-year-old man on maintenance dialysis developed hypotension, nausea and abdominal pain one hour after beginning to undergo hemodialysis. Abdominal computed tomography (CT) showed gas shadows in the intrahepatic portal vein and the small intestinal wall, but no signs indicating intestinal necrosis. Three days later, the gas shadows on abdominal CT disappeared by conservative therapy. In cases with both pneumatosis cystoides intestinalis and hepatic portal venous gas, intestinal necrosis should therefore be suspected and surgical therapy should also be considered, particularly in hemodialysis patients with a risk of intestinal ischemia. However, conservative therapy may be an option in cases with no intestinal necrosis. PMID- 27374674 TI - Successful Endoscopic Treatment of an Actively Bleeding Jejunal Dieulafoy's Lesion. AB - Although small bowel endoscopy is commonly performed, cases of ongoing bleeding from small bowel lesions have not been commonly encountered. In the present report, we describe a case of successful endoscopic treatment of an actively bleeding jejunal Dieulafoy's lesion in a 79-year-old man with persistent anemia and melena. Capsule endoscopy indicated active bleeding in the jejunum. Thereafter, double-balloon endoscopy-performed via the oral approach-showed active bleeding from a jejunal Dieulafoy's lesion, which was treated using argon plasma coagulation and hemoclips. The melena subsequently resolved, and the patient's condition improved after the endoscopic treatment. PMID- 27374676 TI - Refractory Hypotension after Cardioversion in a Patient with Atrial Fibrillation and Congestive Heart Failure. AB - A 63-year-old woman with atrial fibrillation visited our hospital due to decompensated heart failure. Because atrial fibrillation was considered a remarkable precipitating factor for heart failure, cardioversion was performed. After cardioversion, refractory hypotension and cardiopulmonary arrest occurred. An arterial blood gas analysis showed marked lactic acidosis. Chronic kidney disease, heart failure, sedatives, and hypoventilation might have contributed to refractory hypotension due to severe acidosis in this case. PMID- 27374675 TI - Successful Pancreatic Duct Stent Placement for Recurrent Pancreatitis in a Patient with Polysplenia with Agenesis of the Dorsal Pancreas and Peutz-Jeghers Syndrome. AB - A 52-year-old woman presented with relapsing acute pancreatitis. A contrast CT scan revealed polysplenia, agenesis of the dorsal pancreas, preduodenal portal vein, inferior vena cava with persistent continuity of the azygos vein, abnormal lung lobation with bilateral left bronchial morphology, and intestinal malrotation (non-rotation type). To the best of our knowledge, this is the first report in which successful pancreatic duct stent placement for the treatment of recurrent pancreatitis was performed in a polysplenia patient with agenesis of the dorsal pancreas, separate bile and pancreatic ducts and Peutz-Jeghers syndrome. PMID- 27374677 TI - Frequent Premature Ventricular Complexes Originating from the Left Ventricular Summit Successfully Ablated from the Proximal Great Cardiac Vein Using an Impedance-based Electroanatomical Mapping System. AB - We herein report a 58-year-old woman with frequent premature ventricular complexes (PVCs) originating from the left ventricular summit. The earliest ventricular activation of spontaneous PVCs was recorded in the proximal site of the great cardiac vein, which was simultaneously mapped and conducted using an impedance-based electroanatomical mapping system. Irrigated radiofrequency with a starting power output of 20 W and maximal temperature set at 40 degrees C was applied with 10 Omega impedance fall, resulting in total disappearance of the frequent PVCs. The patient has remained free from PVCs for 18 months without requiring antiarrhythmic drug therapy. PMID- 27374678 TI - Non-occlusive Mesenteric Ischemia with Diabetic Ketoacidosis and Lactic Acidosis Following the Administration of a Sodium Glucose Co-transporter 2 Inhibitor. AB - We herein describe a patient with non-occlusive mesenteric ischemia (NOMI) potentially associated with the administration of a sodium glucose co-transporter 2 (SGLT2) inhibitor. A 60-year-old man with type 1 diabetes was transferred to our hospital due to vomiting and respiratory distress. He was treated with insulin, metformin and a SGLT2 inhibitor, which had recently been added. He was diagnosed with intestinal ischemia complicated by diabetic ketoacidosis and lactic acidosis. Urgent exploratory surgery was performed, and the gangrenous bowel was resected. Histological findings confirmed the diagnosis of NOMI. The administration of SGLT2 inhibitors therefore requires certain exceptions for type 1 diabetes and cautious monitoring for the occurrence of these possible adverse effects. PMID- 27374679 TI - Successful Long-term Graft Survival of a Renal Transplantation Patient with Wiskott-Aldrich Syndrome. AB - Wiskott-Aldrich syndrome, a rare X-linked hereditary syndrome, is characterized by immunodeficiency, thrombocytopenia, and eczema. The underlying T-cell defect renders renal transplantation and immunosuppressive treatments uncertain. The present case exhibited the mild clinical manifestation, regarded as X-linked thrombocytopenia. He successfully underwent a living-donor ABO-compatible renal transplantation and splenectomy in 2002, and thereafter experiencing no severe rejection, serious infection, or malignancy for more than 10 years. Though IgA nephropathy was detected 8 months after transplantation, the patient's renal function and proteinuria were stable without any treatment. The present case showed a successful long-term graft survival and the importance of splenectomy added to renal transplantation. PMID- 27374680 TI - Hyponatremic Chloride-depletion Metabolic Alkalosis Successfully Treated with High Cation-gap Amino Acid. AB - Chloride (Cl)-depletion alkalosis (CDA) develops due to the loss of Cl-rich body fluid, i.e., vomiting or diuretics use, and is typically treated with a chloride rich solution such as normal saline (NS). Although NS is one of the most utilized Cl-rich solutions, high cation-gap amino acid (HCG-AA) predominantly comprises Cl and less sodium, making HCG-AA more efficient in correcting CDA. We herein report a case of CDA with chronic hyponatremia after frequent vomiting, which was successfully treated with HCG-AA without overcorrecting hyponatremia or causing hypervolemia. HCG-AA may be more beneficial than NS for treating hyponatremic or hypervolemic metabolic alkalosis. PMID- 27374681 TI - Reactivation of Human Herpes Virus-6 in the Renal Tissue of a Patient with Drug induced Hypersensitivity Syndrome/Drug Rash with Eosinophilia and Systemic Symptoms (DIHS/DRESS). AB - A 74-year-old man who had been administered trimethoprim-sulfamethoxazole for three weeks suffered from drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms (DIHS/DRESS). In the early stage of the clinical course, he developed renal dysfunction. A renal biopsy showed granulomatous tubulointerstitial nephritis accompanying the proliferation of human herpes virus (HHV)-6 in tubular epithelial cells. With corticosteroid therapy, the systemic rash and renal function gradually improved. The present patient is the second case of DIHS/DRESS demonstrating a possible reactivation of HHV-6 in the renal tissue. The clinical role of viral reactivation in DIHS/DRESS must be further elucidated. PMID- 27374682 TI - Changes in Immunohistochemical Protein Levels in Anaplastic Lymphoma Kinase positive Lung Adenocarcinoma Possibly due to Chemo-radiotherapy. AB - To detect the anaplastic lymphoma kinase (ALK) fusion gene in non-small cell lung cancer, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are the standard methods. However, there are discrepancies between them. We herein report a 40-year-old woman with ALK fusion-positive adenocarcinoma that changed from positive to negative in IHC due to chemo-radiotherapy. Recurrence of the disease restored the IHC expression, whereas FISH was positive throughout the entire clinical course. Our experience suggests that we should therefore carefully evaluate samples after chemotherapy and radiotherapy. PMID- 27374683 TI - Pioglitazone-induced Pulmonary Injury in a Very Elderly Patient. AB - An 85-year-old woman with diabetes mellitus was admitted to our hospital due to progressive dyspnea. Two months previously, pioglitazone had been newly prescribed for diabetes management. Bilateral ground-glass opacities and progressive respiratory deterioration suggested respiratory failure due to a drug induced lung injury. With discontinuation of pioglitazone and the administration of a corticosteroid, an improvement in her respiratory condition was achieved, although sequelae remained in some areas of the lungs. Results of drug-induced lymphocyte stimulation tests were positive for pioglitazone. Resumption of other drugs did not reinduce the lung injury. Therefore, a diagnosis of pioglitazone induced lung injury was made. Although pioglitazone-induced lung injury is very rare, clinicians should keep it in mind when pioglitazone is used. PMID- 27374684 TI - Vocal Cord Paralysis and Hypercapnic Respiratory Failure in a Patient with Familial Amyloidotic Polyneuropathy. AB - We herein report a patient case with familial amyloidotic polyneuropathy (FAP) who presented with vocal cord paralysis (VCP). A 60-year-old man with FAP (Gly89Gln) presented with hoarseness and snoring for the previous two years. A chest X-ray demonstrated cardiomegaly and bilateral diaphragmatic elevation. The findings of a restrictive pattern on spirometry and daytime hypercapnia were consistent with respiratory muscle weakness related to neuropathy [forced expiratory volume (FEV1): 38%, forced vital capacity (FVC): 39%, FEV1/FVC: 77, partial pressure of arterial oxygen (PaO2): 80 mmHg, partial pressure of carbon dioxide in arterial blood (PaCO2): 52 mmHg]. An ear-nose-throat examination showed VCP. Polysomnography revealed severe obstructive sleep apnea (OSA). FAP may cause OSA by VCP and hypercapnic respiratory failure by respiratory muscle weakness. Therefore, an ear-nose-throat examination, spirometry, arterial blood gases analysis and polysomnography are important for these patients. PMID- 27374685 TI - Disseminated Mycobacterium abscessus Complex Infection Manifesting as Multiple Areas of Lymphadenitis and Skin Abscess in the Preclinical Stage of Acute Lymphocytic Leukemia. AB - A 37-year-old woman was admitted to a hospital due to a prolonged fever and a rash on her legs. She had systemic lymphadenitis and a skin abscess on her left leg. Pathological findings of a left leg skin biopsy revealed abscess formation with granulomatous dermatitis, Mycobacterium abscessus complex was cultured from the resected left supraclavicular lymph node, and disseminated M. abscessus complex infection was diagnosed. She was treated with combination treatment with antimicrobials and percutaneous drainage, and her clinical findings improved. Four months later, she developed acute lymphocytic leukemia. Leukemia is a risk factor for disseminated M. abscessus complex infection, even before developing leukemia. PMID- 27374686 TI - Ascites Retention during Mogamulizumab Treatment in a Patient with Adult T-cell Leukemia/lymphoma. AB - A 74-year-old woman with refractory adult T-cell leukemia/lymphoma (ATLL) received three courses of mogamulizumab. Despite obtaining complete remission, she thereafter presented with progressive ascites. An analysis of the ascites and laboratory tests revealed no evidence of ATLL invasion, infectious disease, or liver cirrhosis. The mogamulizumab concentrations were maintained in the ascites at approximately 10-15% of that in the plasma. Mogamulizumab was considered to be a plausible pathogenesis of her ascites. To the best of our knowledge, this is the first report suggesting mogamulizumab-induced ascites. PMID- 27374687 TI - Recurrent Attacks of Hypokalemic Quadriparesis: An Unusual Presentation of Primary Sjogren Syndrome. AB - We herein report the case of a 64-year old woman with recurrent attacks of hypokalemic quadriparesis which resulted from distal renal tubular acidosis (dRTA) secondary to Sjogren syndrome. The patient presented with sudden onset quadriparesis. A physical examination showed symmetric weakness of all four limbs. Severe hypokalemia (1.8 mEq/L), accompanied by normal anion gap metabolic acidosis, a positive urine anion gap and an inappropriately high urine pH pointed toward the diagnosis of dRTA. Further investigations disclosed primary Sjogren syndrome, which had not previously been recognized. On the basis of the current report and a review of the literature we suggest investigating the possibility of Sjogren syndrome in all patients with clinically unexplained dRTA. PMID- 27374688 TI - Large Vessel Vasculitis with an Isolated Lesion of a Single-lobe Pulmonary Artery. AB - Chronic pulmonary arterial obstructions are caused mostly by chronic pulmonary artery thromboembolism and rarely by vasculitis or intimal sarcoma of the pulmonary artery. We herein report an unusual case of a 42-year-old woman with a solitary obstruction of the pulmonary artery in the right lower lobe of her lung. Because we could not exclude the possibility of intimal sarcoma, middle and lower lobectomy was performed. The resected specimens revealed large vessel vasculitis (LVV) and an isolated lesion in the right lower lobe pulmonary artery. LVV should therefore be considered in the differential diagnosis for single pulmonary arterial stenosis or obstruction. PMID- 27374689 TI - Persistent Infection of Drug-resistant Influenza A Virus during Chemotherapy for Malignant Lymphoma. AB - We herein report the case of an 80-year-old man with malignant lymphoma who became persistently infected with influenza A virus. Although he was repeatedly treated with NA inhibitors, such as oseltamivir or peramivir, nasal cavity swab tests for influenza A antigen continued to be positive for more than 2 months. Virological analyses revealed that he was infected with the NA inhibitor resistant A (H3N2) virus possessing an R292K substitution in the NA protein. These findings suggest that a drug-resistant influenza virus strain might selectively survive antiviral therapy in elderly patients with refractory malignant lymphoma undergoing multiple chemotherapies. PMID- 27374690 TI - Adult-onset Invasive Haemophilus influenzae Type f Caused by Acute Lower Leg Cellulitis. AB - In Japan, routine Haemophilus influenzae type b (Hib) vaccination began in 2013. Thus, similar to other countries, a strain shift is expected in the near future. We experienced a case of H. influenzae type f (Hif) bacteremia in a 66-year-old man. The primary focus of the infection was the soft tissue of the left lower leg, which is an extremely rare origin in adults. Subsequently, we conducted multilocus sequence typing and identified the strain as sequence type 124, which is the most common invasive strain of Hif worldwide. This case may mark the beginning of an Hif strain shift in Japan. PMID- 27374691 TI - Dabigatran-induced Exfoliative Esophagitis. PMID- 27374692 TI - White Feces Caused by the Administration of a Somatostatin Analogue. PMID- 27374693 TI - Congenital Splenic Hypoplasia in an Elderly Patient. PMID- 27374694 TI - Acute Myeloid Leukemia-associated Charcot-Leyden Crystals in the Bone Marrow. PMID- 27374695 TI - Isolated Lateral Ventricle. PMID- 27374696 TI - Olecranon Osteomyelitis Caused by Mycobacterium chelonae. PMID- 27374697 TI - Aggregation Pheromone Activity of the Female Sex Pheromone, beta-Acaridial, in Caloglyphus polyphyllae (Acari: Acaridae). AB - Caloglyphus (=Sancasania) polyphyllae discharges from a pair of opisthonotal glands a characteristic set of volatiles, i.e. three monoterpenes and seven hydrocarbons. Among them, beta-acaridial, which is known as the female sex pheromone of the species and has antifungal activity, was newly identified as the aggregation pheromone for unfeeding and unmating mites. Feeding mites, however, exhibited sexually aroused behavior instead of the tendency to cluster when exposed to beta-acaridial. This is the first example of the compound demonstrating two pheromone functions depending upon the circumstances faced by the mites. PMID- 27374698 TI - Alcohols as molecular probes in ionic liquids: evidence for nanostructuration. AB - A comprehensive study of the solution and solvation of linear alcohols (propan-1 ol, butan-1-ol and pentan-1-ol) in ionic liquids (ILs) is presented. The effect of the alkyl chain size of both alcohols and ILs (1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [CnC1im][NTf2], ionic liquid series) on the thermodynamic properties of solution and solvation was used to obtain insight into the interactions between alcohols and ILs. Alcohols were used as molecular probes to ascertain whether their solvation in ILs would reflect IL nanostructuration. A trend shift was found in the values of enthalpy of solution and solvation for the [CnC1im][NTf2] series at a critical alkyl size (CAS) of C6. Further, the effect of the hydrogen bond basicity of the anion in the solvation of alcohols was explored based on the comparative study of the solvation of propan-1-ol in two different IL series, 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [CnC1im][NTf2] and hexafluorophosphate [CnC1im][PF6]. The results obtained provide experimental support for the strength of hydrogen bonds between the alcohols and the NTf2 and PF6 anions, providing insights into the IL intermolecular interactions, namely by indicating the ability of the alcohols to discriminate the IL anion hydrogen bond basicity. PMID- 27374699 TI - A hierarchical Zn2Mo3O8 nanodots-porous carbon composite as a superior anode for lithium-ion batteries. AB - A hierarchical Zn2Mo3O8 nanodots-porous carbon composite has been successfully synthesized via the ingenious combination of ion exchange and molten salt strategies, and the composite exhibits remarkable performance as an anode material for lithium-ion batteries. PMID- 27374700 TI - A Review of Supplemental Screening Ultrasound for Breast Cancer: Certain Populations of Women with Dense Breast Tissue May Benefit. AB - Breast density has been shown to be a strong, independent risk factor for breast cancer. Unfortunately, mammography is less accurate on dense breast tissue compared to fattier breast tissue. Multiple studies suggest a solution to this by demonstrating the ability of supplemental screening ultrasound to detect additional malignant lesions in women with dense breast tissue but negative mammography. In particular, supplemental screening ultrasound may be beneficial to women with dense breast tissue and intermediate or average risk for breast cancer, women in specific ethnic populations with greater prevalence of dense breast tissue, and women living in resource-poor healthcare environments. Although magnetic resonance imaging is currently recommended for women with high risk for breast cancer, not all women can access or tolerate a magnetic resonance imaging examination. Notably, ultrasound does not require intravenous gadolinium and may be an alternative for women with socioeconomic or medical restrictions, which limit their access to magnetic resonance imaging. Limitations of supplemental screening ultrasound include a substantial rate of false-positives, increased cost, and limited resource availability, particularly in regard to the time required for image interpretation. Additional clinical experience with this application of ultrasound, improved patient selection criteria, and new technology, such as the promising results seen with automated whole breast ultrasound, may address these limitations. In light of recent legislation in some states that has called for discussing supplemental imaging with patients who have dense breast tissue, the optimal role for supplemental screening ultrasound merits further exploration. PMID- 27374701 TI - DT-13 attenuates human lung cancer metastasis via regulating NMIIA activity under hypoxia condition. AB - Cancer metastasis plays a major role in tumor deterioration. Metastatic processes are known to be regulated by hypoxic microenvironment and non-muscle myosin IIA (NMIIA). DT-13, a bioactive saponin monomer isolated from Ophiopogon japonicus, has been reported to inhibit various cancer metastasis, but whether NMIIA is involved in the anti-metastatic activity of DT-13 under hypoxia remains to be determined. Thus, this study aims to clarify the role of DT-13 in regulating 95D cell metastasis under hypoxic microenvironment and to further investigate whether NMIIA is involved in the anti-metastatic mechanism of DT-13. We found that DT-13 significantly inhibited 95D cells metastasis in vitro and in vivo. Furthermore, hypoxia significantly inhibited the expression of NMIIA and redistributed NMIIA to the cell periphery, whereas DT-13 reversed the hypoxic effects by upregulating the expression of NMIIA. Moreover, DT-13 treatment redistributed NMIIA to the nuclear periphery and reduced the formation of F-actin in 95D cells. In addition, we found that the Raf-ERK1/2 signaling pathway is involved in regulation of NMIIA by DT-13. Collectively, these findings support NMIIA as a target of DT-13 to prevent lung cancer metastasis. PMID- 27374702 TI - Collectively coping with contact: The role of intragroup support in dealing with the challenges of intergroup mixing in residential contexts. AB - The social identity approach to stress has shown how intragroup support processes shape individuals' responses to stress across health care, workplace, and community settings. However, the issue of how these 'social cure' processes can help cope with the stress of intergroup contact has yet to be explored. This is particularly important given the pivotal role of intergroup threat and anxiety in the experience of contact as well as the effect of contact on extending the boundaries of group inclusion. This study applies this perspective to a real-life instance of residential contact in a divided society. Semi-structured interviews with 14 Catholic and 13 Protestant new residents of increasingly mixed areas of Belfast city, Northern Ireland, were thematically analysed. Results highlight that transitioning to mixed communities was fraught with intergroup anxiety, especially for those coming from 'single identity' areas. Help from existing residents, especially when offered by members of other religious denominations, signalled a 'mixed community ethos' to new residents, which facilitated adopting and sharing this identity. This shared identity then enabled them to deal with unexpected intergroup threats and provided resilience to future sectarian division. New residents who did not adopt this shared identity remained isolated, fearful, and prone to negative contact. PMID- 27374703 TI - Correlation of NPM1 Type A Mutation Burden With Clinical Status and Outcomes in Acute Myeloid Leukemia Patients With Mutated NPM1 Type A. AB - BACKGROUND: Nucleophosmin gene (NPM1) mutation may be a good molecular marker for assessing the clinical status and predicting the outcomes in AML patients. We evaluated the applicability of NPM1 type A mutation (NPM1-mutA) quantitation for this purpose. METHODS: Twenty-seven AML patients with normal karyotype but bearing the mutated NPM1 were enrolled in the study, and real-time quantitative PCR of NPM1-mutA was performed on 93 bone marrow (BM) samples (27 samples at diagnosis and 56 at follow-up). The NPM1-mutA allele burdens (represented as the NPM1-mutA/Abelson gene (ABL) ratio) at diagnosis and at follow-up were compared. RESULTS: The median NPM1-mutA/ABL ratio was 1.3287 at diagnosis and 0.092 at 28 days after chemotherapy, corresponding to a median log10 reduction of 1.7061. Significant correlations were observed between BM blast counts and NPM1-mutA quantitation results measured at diagnosis (gamma=0.5885, P=0.0012) and after chemotherapy (gamma=0.5106, P=0.0065). Total 16 patients achieved morphologic complete remission at 28 days after chemotherapy, and 14 (87.5%) patients showed a >3 log10 reduction of the NPM1-mutA/ABL ratio. The NPM1-mutA allele was detected in each of five patients who had relapsed, giving a median increase of 0.91-fold of the NPM1-mutA/ABL ratio at relapse over that at diagnosis. CONCLUSIONS: The NPM1-mutA quantitation results corresponded to BM assessment results with high stability at relapse, and could predict patient outcomes. Quantitation of the NPM1-mutA burden at follow-up would be useful in the management of AML patients harboring this gene mutation. PMID- 27374704 TI - Can a Point-of-Care Troponin I Assay be as Good as a Central Laboratory Assay? A MIDAS Investigation. AB - BACKGROUND: We aimed to compare the diagnostic accuracy of the Alere Triage Cardio3 Tropinin I (TnI) assay (Alere, Inc., USA) and the PathFast cTnI-II (Mitsubishi Chemical Medience Corporation, Japan) against the central laboratory assay Singulex Erenna TnI assay (Singulex, USA). METHODS: Using the Markers in the Diagnosis of Acute Coronary Syndromes (MIDAS) study population, we evaluated the ability of three different assays to identify patients with acute myocardial infarction (AMI). The MIDAS dataset, described elsewhere, is a prospective multicenter dataset of emergency department (ED) patients with suspected acute coronary syndrome (ACS) and a planned objective myocardial perfusion evaluation. Myocardial infarction (MI) was diagnosed by central adjudication. RESULTS: The C statistic with 95% confidence intervals (CI) for diagnosing MI by using a common population (n=241) was 0.95 (0.91-0.99), 0.95 (0.91-0.99), and 0.93 (0.89-0.97) for the Triage, Singulex, and PathFast assays, respectively. Of samples with detectable troponin, the absolute values had high Pearson (R(P)) and Spearman (R(S)) correlations and were R(P)=0.94 and R(S)=0.94 for Triage vs Singulex, R(P)=0.93 and R(S)=0.85 for Triage vs PathFast, and R(P)=0.89 and R(S)=0.73 for PathFast vs Singulex. CONCLUSIONS: In a single comparative population of ED patients with suspected ACS, the Triage Cardio3 TnI, PathFast, and Singulex TnI assays provided similar diagnostic performance for MI. PMID- 27374705 TI - Performance Evaluation of the Serum Thyroglobulin Assays With Immunochemiluminometric Assay and Immunoradiometric Assay for Differentiated Thyroid Cancer. AB - BACKGROUND: Measurement of postoperative serum thyroglobulin (Tg) is important for detecting persistent or recurrent differentiated thyroid cancer. We evaluated the analytic performance of the DxI 800 assay (Beckman Coulter, USA) for serum Tg and anti-thyroglobulin antibodies (TgAbs) in comparison with that of the GAMMA-10 assay (Shinjin Medics Inc., Korea) for serum Tg and RIA-MAT 280 assay (Stratec, Germany) for TgAb. METHODS: We prospectively collected blood samples from 99 patients thyroidectomized for thyroid cancer. The functional sensitivity was investigated in standards and human serum. Precision and linearity were evaluated according to the guidelines of the Clinical and Laboratory Standards Institute. The correlation between the two assays was assessed in samples with different Tg ranges. RESULTS: The functional sensitivity of the DxI 800 assay for serum Tg was between 0.0313 and 0.0625 ng/mL. The total CV was 3.9-5.6% for serum Tg and 5.3 6.9% for serum TgAb. The coefficient of determination (R2) was 1.0 and 0.99 for serum Tg and TgAb, respectively. The cut-offs for serum TgAb were 4.0 IU/mL (DxI 800) and 60.0 IU/mL (RIA-MAT 280), and the overall agreement was 68.7%. The correlation between the two assays was excellent; the correlation coefficient was 0.99 and 0.88 for serum Tg and TgAb, respectively. CONCLUSIONS: The DxI 800 is a sensitive assay for serum Tg and TgAb, and the results correlated well with those from the immunoradiometric assays (IRMA). This assay has several advantages over the IRMA and could be considered an alternative test for Tg measurement. PMID- 27374706 TI - The Prognostic Value of Serum Levels of Heart-Type Fatty Acid Binding Protein and High Sensitivity C-Reactive Protein in Patients With Increased Levels of Amino Terminal Pro-B Type Natriuretic Peptide. AB - BACKGROUND: Amino-terminal pro-B type natriuretic peptide (NT-proBNP) is a well established prognostic factor in heart failure (HF). However, numerous causes may lead to elevations in NT-proBNP, and thus, an increased NT-proBNP level alone is not sufficient to predict outcome. The aim of this study was to evaluate the utility of two acute response markers, high sensitivity C-reactive protein (hsCRP) and heart-type fatty acid binding protein (H-FABP), in patients with an increased NT-proBNP level. METHODS: The 278 patients were classified into three groups by etiology: 1) acute coronary syndrome (ACS) (n=62), 2) non-ACS cardiac disease (n=156), and 3) infectious disease (n=60). Survival was determined on day 1, 7, 14, 21, 28, 60, 90, 120, and 150 after enrollment. RESULTS: H-FABP (P<0.001), NT-proBNP (P=0.006), hsCRP (P<0.001) levels, and survival (P<0.001) were significantly different in the three disease groups. Patients were divided into three classes by using receiver operating characteristic curves for NT proBNP, H-FABP, and hsCRP. Patients with elevated NT-proBNP (>=3,856 pg/mL) and H FABP (>=8.8 ng/mL) levels were associated with higher hazard ratio for mortality (5.15 in NT-proBNP and 3.25 in H-FABP). Area under the receiver operating characteristic curve analysis showed H-FABP was a better predictor of 60-day mortality than NT-proBNP. CONCLUSIONS: The combined measurement of H-FABP with NT proBNP provides a highly reliable means of short-term mortality prediction for patients hospitalized for ACS, non-ACS cardiac disease, or infectious disease. PMID- 27374707 TI - Evaluation of Serum Cotinine Cut-Off to Distinguish Smokers From Nonsmokers in the Korean Population. AB - BACKGROUND: Cotinine has been widely used as an objective marker to identify current smokers. We conducted this study to address the absence of Korean studies investigating the efficacy of immunoassays and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the detection of serum cotinine and to determine the optimal serum cotinine cut-off level for differentiating current smokers from nonsmokers. METHODS: Serum specimens were obtained from 120 subjects. They were randomly chosen to represent a broad distribution of urine cotinine levels based on a retrospective review of questionnaires and results of urine cotinine levels. We determined serum cotinine levels using the IMMULITE 2000 XPi Immunoassay System (Siemens Healthcare Diagnostics Inc., USA) and LC-MS/MS (API-4000, Applied Biosystems, USA). Correlation was analyzed between IMMULITE serum cotinine, urine cotinine, and LC-MS/MS serum cotinine levels. ROC curve was analyzed to identify the optimal IMMULITE serum cotinine cut-off level for differentiating current smokers from nonsmokers. RESULTS: IMMULITE serum cotinine levels correlated with both urine cotinine and LC-MS/MS serum cotinine levels, with correlation coefficients of 0.958 and 0.986, respectively. The optimal serum cotinine cut-off level for distinguishing current smokers from nonsmokers was 13.2 ng/mL (95.7% sensitivity, 94.1% specificity) using IMMULITE. CONCLUSIONS: This is the first study to investigate the use of LC-MS/MS for the measurement of serum cotinine and to determine the optimal serum cotinine cut-off level for the IMMULITE immunoassay. Our results could provide guidelines for differentiating current smokers from nonsmokers in the Korean population. PMID- 27374708 TI - Disk Carbapenemase Test for the Rapid Detection of KPC-, NDM-, and Other Metallo beta-Lactamase-Producing Gram-Negative Bacilli. AB - BACKGROUND: Rapid detection of carbapenemase-producing gram-negative bacilli (GNB) is required for optimal treatment of infected patients. We developed and assessed a new disk carbapenemase test (DCT). METHODS: Paper disks containing 0.3 mg of imipenem and bromothymol blue indicator were developed, and the performance of the DCT were evaluated by using 742 strains of GNB with or without carbapenemases. RESULTS: The paper disks were simple to prepare, and the dried disks were stable at -20 degrees C and at 4 degrees C. The DCT detected 212 of 215 strains (98.6% sensitivity with 95% confidence interval [CI] 96.0-99.5%) of GNB with known class A (KPC and Sme) and class B (NDM, IMP, VIM, and SIM) carbapenemases within 60 min, but failed to detect GES-5 carbapenemase. The DCT also detected all two Escherichia coli isolates with OXA-48, but failed to detect GNB with OXA-232, and other OXA carbapenemases. The DCT showed 100% specificity (95% CI, 99.2-100%) in the test of 448 imipenem-nonsusceptible, but carbapenemase genes not tested, clinical isolates of GNB. CONCLUSIONS: The DCT is simple and can be easily performed, even in small laboratories, for the rapid detection of GNB with KPC, NDM and the majority of IMP, VIM, and SIM carbapenemases. PMID- 27374709 TI - Analysis of the Vaginal Microbiome by Next-Generation Sequencing and Evaluation of its Performance as a Clinical Diagnostic Tool in Vaginitis. AB - BACKGROUND: Next-generation sequencing (NGS) can detect many more microorganisms of a microbiome than traditional methods. This study aimed to analyze the vaginal microbiomes of Korean women by using NGS that included bacteria and other microorganisms. The NGS results were compared with the results of other assays, and NGS was evaluated for its feasibility for predicting vaginitis. METHODS: In total, 89 vaginal swab specimens were collected. Microscopic examinations of Gram staining and microbiological cultures were conducted on 67 specimens. NGS was performed with GS junior system on all of the vaginal specimens for the 16S rRNA, internal transcribed spacer (ITS), and Tvk genes to detect bacteria, fungi, and Trichomonas vaginalis. In addition, DNA probe assays of the Candida spp., Gardnerella vaginalis, and Trichomonas vaginalis were performed. Various predictors of diversity that were obtained from the NGS data were analyzed to predict vaginitis. RESULTS: ITS sequences were obtained in most of the specimens (56.2%). The compositions of the intermediate and vaginitis Nugent score groups were similar to each other but differed from the composition of the normal score group. The fraction of the Lactobacillus spp. showed the highest area under the curve value (0.8559) in ROC curve analysis. The NGS and DNA probe assay results showed good agreement (range, 86.2-89.7%). CONCLUSIONS: Fungi as well as bacteria should be considered for the investigation of vaginal microbiome. The intermediate and vaginitis Nugent score groups were indistinguishable in NGS. NGS is a promising diagnostic tool of the vaginal microbiome and vaginitis, although some problems need to be resolved. PMID- 27374710 TI - Analytical and Clinical Validation of Six Commercial Middle East Respiratory Syndrome Coronavirus RNA Detection Kits Based on Real-Time Reverse-Transcription PCR. AB - BACKGROUND: During the 2015 outbreak of Middle East Respiratory Syndrome coronavirus (MERS-CoV), six different commercial MERS-CoV RNA detection kits based on real-time reverse-transcription polymerase chain reaction (rRT-PCR) were available in Korea. We performed analytical and clinical validations of these kits. METHODS: PowerChek (Kogene Biotech, Korea), DiaPlexQ (SolGent, Korea), Anyplex (Seegene, Korea), AccuPower (Bioneer, Korea), LightMix (Roche Molecular Diagnostics, Switzerland), and UltraFast kits (Nanobiosys, Korea) were evaluated. Limits of detection (LOD) with 95% probability values were estimated by testing 16 replicates of upstream of the envelope gene (upE) and open reading frame 1a (ORF1a) RNA transcripts. Specificity was estimated by using 28 nasopharyngeal swabs that were positive for other respiratory viruses. Clinical sensitivity was evaluated by using 18 lower respiratory specimens. The sensitivity test panel and the high inhibition panel were composed of nine specimens each, including eight and six specimens that were positive for MERS-CoV, respectively. RESULTS: The LODs for upE ranged from 21.88 to 263.03 copies/reaction, and those for ORF1a ranged from 6.92 to 128.82 copies/reaction. No cross-reactivity with other respiratory viruses was found. All six kits correctly identified 8 of 8 (100%) positive clinical specimens. Based on results from the high inhibition panel, PowerChek and AccuPower were the least sensitive to the presence of PCR inhibition. CONCLUSIONS: The overall sensitivity and specificity of all six assay systems were sufficient for diagnosing MERS-CoV infection. However, the analytical sensitivity and detection ability in specimens with PCR inhibition could be improved with the use of appropriate internal controls. PMID- 27374711 TI - Comparative Evaluation of Three Homogenization Methods for Isolating Middle East Respiratory Syndrome Coronavirus Nucleic Acids From Sputum Samples for Real-Time Reverse Transcription PCR. AB - BACKGROUND: Real-time reverse transcription PCR (rRT-PCR) of sputum samples is commonly used to diagnose Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Owing to the difficulty of extracting RNA from sputum containing mucus, sputum homogenization is desirable prior to nucleic acid isolation. We determined optimal homogenization methods for isolating viral nucleic acids from sputum. METHODS: We evaluated the following three sputum-homogenization methods: proteinase K and DNase I (PK-DNase) treatment, phosphate-buffered saline (PBS) treatment, and N-acetyl-L-cysteine and sodium citrate (NALC) treatment. Sputum samples were spiked with inactivated MERS-CoV culture isolates. RNA was extracted from pretreated, spiked samples using the easyMAG system (bioMerieux, France). Extracted RNAs were then subjected to rRT-PCR for MERS-CoV diagnosis (DiaPlex Q MERS-coronavirus, SolGent, Korea). RESULTS: While analyzing 15 spiked sputum samples prepared in technical duplicate, false-negative results were obtained with five (16.7%) and four samples (13.3%), respectively, by using the PBS and NALC methods. The range of threshold cycle (Ct) values observed when detecting upE in sputum samples was 31.1-35.4 with the PK-DNase method, 34.7-39.0 with the PBS method, and 33.9-38.6 with the NALC method. Compared with the control, which were prepared by adding a one-tenth volume of 1:1,000 diluted viral culture to PBS solution, the ranges of Ct values obtained by the PBS and NALC methods differed significantly from the mean control Ct of 33.2 (both P<0.0001). CONCLUSIONS: The PK-DNase method is suitable for homogenizing sputum samples prior to RNA extraction. PMID- 27374712 TI - Germline TP53 Mutation and Clinical Characteristics of Korean Patients With Li Fraumeni Syndrome. AB - BACKGROUND: Little is known of the mutation and tumor spectrum of Korean patients with Li-Fraumeni syndrome (LFS). Owing to the rarity of LFS, few cases have been reported in Korea thus far. This study aimed to retrospectively review the mutations and clinical characteristics of Korean patients with LFS. METHODS: TP53 mutation was screened in 89 unrelated individuals at the Samsung Medical Center in Korea, from 2004 to 2015. Six additional mutation carriers were obtained from the literature. RESULTS: We identified nine different mutations in 14 Korean patients (male to female ratio=0.3:1). Two such frameshift mutations (p.Pro98Leufs*25, p.Pro27Leufs*17) were novel. The recurrent mutations were located at codons 31 (n=2; p.Val31Ile), 175 (n=3; p.Arg175His), and 273 (n=4; p.Arg273His and p.Arg273Cys). The median age at the first tumor onset was 25 yr. Ten patients (71%) developed multiple primary tumors. A diverse spectrum of tumors was observed, including breast (n=6), osteosarcoma (n=4), brain (n=4), leukemia (n=2), stomach (n=2), thyroid (n=2), lung (n=2), skin (n=2), bladder (n=1), nasal cavity cancer (n=1), and adrenocortical carcinoma (n=1). CONCLUSIONS: There was considerable heterogeneity in the TP53 mutations and tumor spectrum in Korean patients with LFS. Our results suggest shared and different LFS characteristics between Caucasian and Korean patients. This is the first report on the mutation spectrum and clinical characteristics from the largest series of Korean LFS patients. PMID- 27374713 TI - Adeno-Associated Virus 2-Mediated Hepatocellular Carcinoma is Very Rare in Korean Patients. AB - BACKGROUND: The incidence and etiology of hepatocellular carcinoma (HCC) vary widely according to race and geographic regions. The insertional mutagenesis of adeno-associated virus 2 (AAV2) has recently been considered a new viral etiology of HCC. The aim of this study was to investigate the frequency and clinical characteristics of AAV2 in Korean patients with HCC. METHODS: A total of 289 unrelated Korean patients with HCC, including 159 Hepatitis-B-related cases, 16 Hepatitis-C-related cases, and 114 viral serology-negative cases, who underwent surgery at the Samsung Medical Center in Korea from 2009 to 2014 were enrolled in this study. The presence of AAV2 in fresh-frozen tumor tissues was investigated by DNA PCR and Sanger sequencing. The clinical and pathological characteristics of AAV2-associated HCC in these patients were compared with previous findings in French patients. RESULTS: The AAV2 detection rate in Korean patients (2/289) was very low compared with that in French patients (11/193). Similar to the French patients, the Korean patients with AAV2-related HCC showed no signs of liver cirrhosis. The Korean patients were younger than the French patients with the same AAV2-associated HCC; the ages at diagnosis of the two Korean patients were 47 and 39 yr, while the median age of the 11 French patients was 55 yr (range 43 90 yr). CONCLUSIONS: AAV2-associated HCC was very rare in Korean patients with HCC. Despite a limited number of cases, this study is the first to report the clinical characteristics of Korean patients with AAV2-associated HCC. These findings suggest epidemiologic differences in viral hepatocarcinogenesis between Korean and European patients. PMID- 27374714 TI - Frequency and Clinical Characteristics of Intrachromosomal Amplification of Chromosome 21 in Korean Childhood B-lineage Acute Lymphoblastic Leukemia. AB - BACKGROUND: Intrachromosomal amplification of chromosome 21 (iAMP21) is known to be associated with poor prognosis in B-cell ALL (B-ALL). To determine the frequency and clinical characteristics of iAMP21 in Korean B-ALL patients, we performed FISH and multiplex ligation-dependent probe amplification (MLPA) analyses. METHODS: A total of 102 childhood B-ALL patients were screened with ETV6-RUNX1 FISH probes (Abbott Molecular, USA). The presence of an iAMP21 was confirmed by using MLPA P327 iAMP21-ERG probemix (MRC Holland, The Netherlands). RESULTS: iAMP21 was detected in one of the screened B-ALL patients (1/102 patients, 1.0%) who presented the ALL immunophenotype and complex karyotype at initial diagnosis. The patient relapsed twice after bone marrow transplantation. MLPA showed 12.5-Mb and 4.28-Mb regions of amplification and deletion, respectively. CONCLUSIONS: The frequency of iAMP21 is considerable in Korean pediatric patients. Our report suggests that iAMP21 in childhood B-ALL has very unfavorable impact on patient's prognosis. Additional methods such as MLPA analysis is essential to rule out patients with equivocal interphase FISH results. PMID- 27374715 TI - Reference Intervals of Hematology and Clinical Chemistry Analytes for 1-Year-Old Korean Children. AB - BACKGROUND: Reference intervals need to be established according to age. We established reference intervals of hematology and chemistry from community-based healthy 1-yr-old children and analyzed their iron status according to the feeding methods during the first six months after birth. METHODS: A total of 887 children who received a medical check-up between 2010 and 2014 at Boramae Hospital (Seoul, Korea) were enrolled. A total of 534 children (247 boys and 287 girls) were enrolled as reference individuals after the exclusion of data obtained from children with suspected iron deficiency. Hematology and clinical chemistry analytes were measured, and the reference value of each analyte was estimated by using parametric (mean+/-2 SD) or nonparametric methods (2.5-97.5th percentile). Iron, total iron-binding capacity, and ferritin were measured, and transferrin saturation was calculated. RESULTS: As there were no differences in the mean values between boys and girls, we established the reference intervals for 1-yr old children regardless of sex. The analysis of serum iron status according to feeding methods during the first six months revealed higher iron, ferritin, and transferrin saturation levels in children exclusively or mainly fed formula than in children exclusively or mainly fed breast milk. CONCLUSIONS: We established reference intervals of hematology and clinical chemistry analytes from community based healthy children at one year of age. These reference intervals will be useful for interpreting results of medical check-ups at one year of age. PMID- 27374716 TI - Multiplex Assay of Second-Line Anti-Tuberculosis Drugs in Dried Blood Spots Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry. AB - As dried blood spots (DBSs) have various advantages over conventional venous blood sampling, some assays for detection of one or two anti-tuberculosis (TB) drugs in DBSs have been developed. However, there are no assays currently available for the simultaneous measurement of three or more anti-TB drugs in DBSs. In this study, we developed and evaluated a multiplex method for detecting nine anti-TB drugs including streptomycin, kanamycin, clarithromycin, cycloserine, moxifloxacin, levofloxacin, para-aminosalicylic acid, prothionamide, and linezolid in DBSs by using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Seventy-nine patient samples of DBS were analyzed on the UPLC-MS/MS system. All drug concentrations were determined within 4 min, and assay performance was evaluated. All drugs were clearly separated without ion suppression. Within-run and between-run precisions were 1.7-13.0% and 5.7-17.0%, respectively, at concentrations representing low and high levels for the nine drugs. Lower limits of detection and quantification were 0.06-0.6 and 0.5-5.0 MUg/mL, respectively. Linearity was acceptable at five level concentrations for each drug. Correlations between drug concentrations in plasma and DBSs by using Passing-Bablock regression and Pearson's rho (rho 0.798-0.989) were acceptable. In conclusion, we developed a multiplex assay to measure nine second-line anti-TB drugs in DBSs successfully. This assay provided convenient and rapid drug quantification and could have applications in drug monitoring during treatment. PMID- 27374717 TI - Acute Myeloid Leukemia With MLL Rearrangement and CD4+/CD56+ Expression can be Misdiagnosed as Blastic Plasmacytoid Dendritic Cell Neoplasm: Two Case Reports. PMID- 27374718 TI - Reply to the Letter to the Editor by Dr. Chirumbolo. PMID- 27374719 TI - Basophil Activation Test for Chronic Urticaria. PMID- 27374721 TI - Erratum: Increase in Anti-Gal IgM Level is Associated With Early Graft Failure in Intraportal Porcine Islet Xenotransplantation. AB - This corrects the article on p. 611 in vol. 35, PMID: 26354349. PMID- 27374720 TI - MLL-SEPT5 Fusion Transcript in Two de novo Acute Myeloid Leukemia Patients With t(11;22)(q23;q11). PMID- 27374722 TI - Endogenous glucocorticoids exacerbate cholestasis-associated liver injury and hypercholesterolemia in mice. AB - Cholestatic liver disease is characterized by a disruption of bile flow, bile acid toxicity, liver injury, and hypercholesterolemia. Relatively high secretion of glucocorticoids by the adrenals has been observed under cholestatic conditions. Here we investigated a contribution of the rise in endogenous glucocorticoids to initial stage cholestasis pathology. Adrenalectomized or sham operated control C57BL/6 mice were given an oral dose of alpha naphthylisothiocyanate to induce cholestasis. Adrenalectomy effectively lowered plasma corticosterone levels (18+/-5ng/ml vs 472+/-58ng/ml; P<0.001) and disrupted the metabolic and anti-inflammatory glucocorticoid function. Adrenal removal did not exacerbate the cholestasis extent. In contrast, the cholestasis associated liver injury was markedly lower in adrenalectomized mice as compared to controls as evidenced by a 84%-93% decrease in liver necrosis and plasma alanine aminotransferase and bile acid levels (P<0.001 for all). Gene expression analysis on livers from adrenalectomized mice suggested the absence of bile acid toxicity-associated farnesoid X receptor signaling in the context of a 44% (P<0.01) and 82% (P<0.001) reduction in sodium/bile acid cotransporter member 1 transcript level as compared to respectively control and non-diseased mice. Adrenalectomy reduced the expression of the cholesterol synthesis gene HMG-CoA reductase by 70% (P<0.05), which translated into a 73% lower plasma total cholesterol level (P<0.05). Treatment of C57BL/6 mice with the glucocorticoid receptor antagonist RU-486 recapitulated the protective effect of adrenalectomy on indices of liver injury and hypercholesterolemia. In conclusion, we have shown that endogenous glucocorticoids exacerbate the liver injury and hypercholesterolemia associated with acute cholestasis in mice. PMID- 27374724 TI - Use of Flexi-Seal to manage early colostomy complications. PMID- 27374723 TI - Fetal movements as a predictor of health. AB - The key determinant to a fetus maintaining its health is through adequate perfusion and oxygen transfer mediated by the functioning placenta. When this equilibrium is distorted, a number of physiological changes, including reduced fetal growth, occur to favor survival. Technologies have been developed to monitor these changes with a view to prolong intrauterine maturity while reducing the risks of stillbirth. Many of these strategies involve complex interpretation, for example Doppler ultrasound for fetal blood flow and computerized analysis of fetal heart rate changes. However, even with these modalities of fetal assessment to determine the optimal timing of delivery, fetal movements remain integral to clinical decision-making. In high-risk cohorts with fetal growth restriction, the manifestation of a reduction in perceived movements may warrant an expedited delivery. Despite this, there has been little evolution in the development of technologies to objectively evaluate fetal movement behavior for clinical application. This review explores the available literature on the value of fetal movement analysis as a method of assessing fetal wellbeing, and demonstrates how interdisciplinary developments in this area may aid in the improvement of clinical outcomes. PMID- 27374725 TI - Helical Folding Competing with Unfolded Aggregation in Phenylene Ethynylene Foldamers. AB - The folding and aggregation behavior of a pair of oligo(phenylene ethynylene) (OPE) foldamers are investigated by means of UV/Vis absorption and circular dichroism spectroscopy. With identical OPE backbones, two foldamers, 1 with alkyl side groups and 2 with triethylene glycol side chains, manifest similar helical conformations in solutions in n-hexane and methanol, respectively. However, disparate and competing folding and aggregation processes are observed in alternative solvents. In cyclohexane, oligomer 1 initially adopts the helical conformation, but the self-aggregation of unfolded chains, as a minor component, gradually drives the folding-unfolding transition eventually to the unfolded aggregate state completely. In contrast, in aqueous solution (CH3 OH/H2 O) both folded and unfolded oligomer 2 appear to undergo self-association; aggregates of the folded chains are thermodynamically more stable. In solutions with a high H2 O content, self-aggregation among unfolded oligomers is kinetically favored; these oligomers very slowly transform into aggregates of helical structures with greater thermodynamic stability. The folded-unfolded conformational switch thus takes place with the free (nonaggregated) molecules, and the very slow folding transition is due to the low concentration of molecularly dispersed oligomers. PMID- 27374726 TI - Activity of linezolid and tedizolid against clinical isolates of methicillin resistant and methicillin and linezolid resistant Staphylococcus aureus: an in vitro comparison. AB - OBJECTIVE: The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in Spain is approximately 20-30%. However, resistance to linezolid is rare, and the main reports are from nosocomial outbreaks. The objective of the present study was to compare the in vitro susceptibility of linezolid with that of tedizolid against MRSA isolates and methicillin-and linezolid-resistant isolates (MLRSA) mediated by the cfr gene. METHODS: The in vitro susceptibility of linezolid and tedizolid was determined using the E-test with 18 MRSA strains and 18 cfr-mediated MLRSA strains obtained from clinical isolates in the microbiology service of a tertiary university hospital. RESULTS: All MRSA strains were susceptible to both antibiotics. Analysis of the MRSA isolates revealed that the MIC50 and MIC90 of linezolid were 1.5 and 2 mg/L, respectively; those of tedizolid were 0.25 and 0.4 mg/L. The MIC50 and MIC90 of tedizolid remained at 0.75 and 1 mg/L against the MLRSA strains (MIC90 >= 8 mg/L). CONCLUSIONS: Both for MRSA and for MLRSA, the MICs obtained for tedizolid were at least 2 dilutions lower than those of linezolid, thus demonstrating between 2 and 4 times greater activity in vitro than linezolid. PMID- 27374728 TI - Systematic variation of population receptive field properties across cortical depth in human visual cortex. AB - Receptive fields (RFs) in visual cortex are organized in antagonistic, center surround, configurations. RF properties change systematically across eccentricity and between visual field maps. However, it is unknown how center-surround configurations are organized in human visual cortex across lamina. We use sub millimeter resolution functional MRI at 7Tesla and population receptive field (pRF) modeling to investigate the pRF properties in primary visual cortex (V1) across cortical depth. pRF size varies according to a U-shaped function, indicating smaller pRF center size in the middle compared to superficial and deeper intra-cortical portions of V1, consistent with non-human primate neurophysiological measurements. Moreover, a similar U-shaped function is also observed for pRF surround size. However, pRF center-surround ratio remains constant across cortical depth. Simulations suggest that this pattern of results can be directly linked to the flow of signals across cortical depth, with the visual input reaching the middle of cortical depth and then spreading towards superficial and deeper layers of V1. Conversely, blood-oxygenation-level dependent (BOLD) signal amplitude increases monotonically towards the pial surface, in line with the known vascular organization across cortical depth. Independent estimates of the haemodynamic response function (HRF) across cortical depth show that the center-surround pRF size estimates across cortical depth cannot be explained by variations in the full-width half maximum (FWHM) of the HRF. PMID- 27374727 TI - Effects of aging on low luminance contrast processing in humans. AB - Luminance contrast is a fundamental visual cue. Using a dedicated neuroimaging framework, we sought to characterize typical Blood Oxygen Level Dependent (BOLD) responses in two subcortical regions, the superior colliculus (SC) and the lateral geniculate nucleus (LGN), and V1, the primary visual cortex area, and how they change over the lifespan. For imaging subcortical activity related to luminance contrast modulation, specific measurements were introduced to rule out possible signal contamination by cardiovascular activity and vascular alterations with age that could hamper the BOLD signal interpretation. Clearly, BOLD responses increased in these three regions with luminance contrast, with a statistically significant diminution in LGN and V1 for older compared to younger participants, while basal perfusion remained unchanged. Additionally, perceptual responses, as assessed with psychophysical experiments, were highly correlated to BOLD measures in the three studied regions. Taken together, fMRI and psychophysics results indicate an alteration of luminance contrast processing with normal aging. Based on this knowledge we can better recognize when age related brain changes vary from these expectations especially during neurodegenerative diseases progression where the functioning of subcortical structures is altered. The proposed fMRI-physchophysics methodology allows performing such investigation. PMID- 27374729 TI - Reduction of global interference of scalp-hemodynamics in functional near infrared spectroscopy using short distance probes. AB - Functional near-infrared spectroscopy (fNIRS) is used to measure cerebral activity because it is simple and portable. However, scalp-hemodynamics often contaminates fNIRS signals, leading to detection of cortical activity in regions that are actually inactive. Methods for removing these artifacts using standard source-detector distance channels (Long-channel) tend to over-estimate the artifacts, while methods using additional short source-detector distance channels (Short-channel) require numerous probes to cover broad cortical areas, which leads to a high cost and prolonged experimental time. Here, we propose a new method that effectively combines the existing techniques, preserving the accuracy of estimating cerebral activity and avoiding the disadvantages inherent when applying the techniques individually. Our new method accomplishes this by estimating a global scalp-hemodynamic component from a small number of Short channels, and removing its influence from the Long-channels using a general linear model (GLM). To demonstrate the feasibility of this method, we collected fNIRS and functional magnetic resonance imaging (fMRI) measurements during a motor task. First, we measured changes in oxygenated hemoglobin concentration (?Oxy-Hb) from 18 Short-channels placed over motor-related areas, and confirmed that the majority of scalp-hemodynamics was globally consistent and could be estimated from as few as four Short-channels using principal component analysis. We then measured ?Oxy-Hb from 4 Short- and 43 Long-channels. The GLM identified cerebral activity comparable to that measured separately by fMRI, even when scalp hemodynamics exhibited substantial task-related modulation. These results suggest that combining measurements from four Short-channels with a GLM provides robust estimation of cerebral activity at a low cost. PMID- 27374730 TI - Temporal Trends in Conduit Urinary Diversion With Concomitant Cystectomy for Benign Indications: A Population-based Analysis. AB - OBJECTIVE: To describe national trends in cystectomy at the time of urinary diversion for benign indications. Multiple practice patterns exist regarding the necessity for concomitant cystectomy with urinary diversion for benign end-stage lower urinary tract dysfunction. Beyond single-institution reports, limited data are available to describe how concurrent cystectomy is employed on a national level. MATERIALS AND METHODS: A representative sample of patients undergoing urinary diversion for benign indications with or without concurrent cystectomy was identified from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from 1998 to 2011. Using multivariate logistic regression models, we identified hospital- and patient-level characteristics associated with concomitant cystectomy with urinary diversion. RESULTS: There was an increase in the proportion of concomitant cystectomy at the time of urinary diversion from 20% to 35% (P < .001) between 1998 and 2011. The increase in simultaneous cystectomy over time occurred at teaching hospitals (vs community hospitals), in older patients, in male patients, in the Medicare population (vs private insurance and Medicaid), and in those with certain diagnoses. CONCLUSION: There has been an overall increase in the use of cystectomy at the time of urinary diversion for benign indications on a national level, although the indications driving this clinical decision appear inconsistent. PMID- 27374731 TI - Antegrade Sclerotherapy to Treat All Types of Varicoceles in the Pediatric Population: Experience of a Single Center. AB - OBJECTIVE: To analyze our experience with antegrade sclerotherapy for the treatment of Coolsaet types I, II, and III varicoceles in a pediatric and adolescent population. MATERIALS AND METHODS: Between 2005 and 2015, 73 patients who underwent antegrade sclerotherapy were retrospectively evaluated. Patient age, side, clinical and Doppler ultrasound grade, and anatomical variations were collected. Varicoceles were grouped following Coolsaet's classification: all types were sclerosed. Follow-up consisted in clinical examination 3 and 6 months following surgery and testicular Doppler ultrasound 6 and 12 months following surgery. Patients were then telephonically interviewed. Success was defined as varicocele resolution or reduction to a grade not requiring surgery. RESULTS: Mean patient age was 14.7 years and mean operating time was 50.8 minutes. Based on phlebographic imaging and following Coolsaet's classification, we identified 57 (78.1%) type I, 3 (4.1%) type II, and 13 (17.8%) type III varicoceles. No intraoperative complications were observed. Three patients (4.1%) presented a short-term complication in the form of pampiniform plexus thrombosis; 1 patient also developed wound dehiscence: all complications occurred in Coolsaet type I varicoceles and during surgeon learning curve. No hydrocele occurred. Out of 59 patients with a satisfactory follow-up (range: 14 months-10 years), 2 recurrences occurred, the success rate thus being 96.6%. CONCLUSION: Tauber's antegrade sclerotherapy is a simple and feasible technique, effective in treating all kinds of varicocele with low complication, recurrence, and persistence rates. Phlebography reveals frequent venous anatomical variations, allows grouping of varicoceles into Coolsaet types, and enables performing of sclerosis safely in all 3 kinds. PMID- 27374732 TI - The Impact of Diabetes Mellitus and Obesity on Artificial Urinary Sphincter Outcomes in Men. AB - OBJECTIVE: To evaluate the impact of diabetes and obesity on artificial urinary sphincter (AUS) outcomes. MATERIALS AND METHODS: From 1987 to 2011, men with available diabetes and body mass index (BMI) information (568 of 954) undergoing primary AUS placement at our institution were evaluated. The incidence of all cause reintervention, mechanical failure, atrophy, and erosion or infection was assessed using the Kaplan-Meier method. Multivariable analyses evaluated the association between clinical characteristics and AUS outcomes. RESULTS: In total, 90 (16%) men had diabetes. Median follow-up among alive men without AUS event was 5.9 years. Diabetics had a greater 5-year incidence of erosion/infection (13% vs 8%; P = .025). On multivariable analysis, diabetes was independently associated with an increased risk of erosion/infection (hazard ratio [HR] = 2.26; P = .02); whereas greater BMI was associated with a reduced risk of erosion or infection (obese: HR = 0.39; P = .02; overweight: HR = 0.57; P = .07). Accordingly, in diabetics, greater average postoperative glucose level (176 mg/dL vs 153 mg/dL; P = .04) and use of nonantibiotic coated devices (13 of 62 vs 1 of 28; P = .035) was associated with a greater incidence of erosion or infection. There was no difference in social continence (<=1 pad/day) (45% vs 57%; P = .29) or high-level satisfaction (95% vs 90%; P = .43) among diabetics vs nondiabetics. However, with greater BMI (<25, 25 to <30, and >=30), there was a decrease in <=1 pad/day usage (62% vs 61% vs 49%; P = .02). CONCLUSION: We found that the presence of diabetes was independently associated with a 2.3-fold increased risk of AUS erosion or infection. These findings warrant the consideration of additional periprocedural measures to reduce the risk of this devastating complication. PMID- 27374733 TI - Occurrence of and Risk Factors for Urological Intervention During Benign Hysterectomy: Analysis of the National Surgical Quality Improvement Program Database. AB - OBJECTIVE: To determine the occurrence of lower genitourinary tract (LGUT) injury during hysterectomy for benign disease and identify risk factors for LGUT injury, with a specific focus on the effect of hysterectomy modality. METHODS: We performed a retrospective cohort study of patients undergoing hysterectomy for benign disease from 2010 t o 2014 using the American College of Surgeons National Surgical Quality Improvement Program, a multi-institutional prospective registry that captures perioperative surgical outcomes. We identified the occurrence of concomitant cystoscopy and therapeutic urologic interventions including endoscopic ureteric stenting, ureteric repair, bladder repair, cystectomy, and urinary diversion as a proxy for LGUT injuries. Adjusted odds ratios and 95% confidence intervals were calculated using multivariate logistic regression. RESULTS: We identified 101,021 patients treated with hysterectomy for benign disease: 18,610 (18.4%), 27,427 (27.2%), and 54,984 (54.4%) underwent vaginal, open, and laparoscopic hysterectomy, respectively. Cystoscopy was performed in 16,493 cases (16.3%). There were 2427 patients (2.4%) who underwent concomitant urologic intervention. Patients undergoing laparoscopic hysterectomy had increased occurrence of urologic intervention, excluding cystoscopy (adjusted odds ratio 1.47, 95% confidence interval 1.29-1.69), compared to vaginal hysterectomy; no differences were found between open and vaginal hysterectomy or laparoscopic and open hysterectomy. Larger uteri, a postoperative diagnosis of endometriosis, increasing comorbidity, and African American race were associated with an increased odd of urologic intervention whereas concomitant cystoscopy was associated with a decreased chance. CONCLUSION: The incidence of lower genitourinary tract intervention in benign hysterectomy is significant and may be higher than previously reported. Predisposing patient factors and operative technique are key risk factors. PMID- 27374734 TI - A Systematic Review of Ileal Conduit and Neobladder Outcomes in Primary Bladder Cancer. AB - Treatment for muscle invasive bladder cancer with curative intent includes radical cystectomy and urinary diversion. Using PRISMA guidelines, we conducted a systematic review assessing differences in patient selection, operative parameters, complications, and quality of life between ileal conduit and neobladder cohorts. Ileal conduit cohorts have more advanced age and disease, more comorbidities and complications, and poorer quality of life. Ileal conduit surgery is associated with adverse patient selection that inhibits reasonable comparison of outcomes with neobladder cohorts. Despite this, we observe longer operative times and hospital stays in neobladder cohorts, perhaps reflecting greater technical difficulty and the need for postoperative bladder training. PMID- 27374735 TI - Immunologic evaluation of the endometrium with a levonorgestrel intrauterine device in solid organ transplant women and healthy controls. AB - OBJECTIVE: The objective was to describe the endometrial milieu of stable transplant patients and healthy women before and after levonorgestrel intrauterine system (LNG-IUS) insertion. STUDY DESIGN: Women between 18 and 45 years of age desiring LNG-IUS insertion were enrolled with a 2:1 ratio of healthy to stable solid organ transplant patients. The first visit entailed a blood draw, uterine lavage and endometrial biopsy followed by LNG-IUS insertion. Follow-up visit involved a repeat serum draw, uterine lavage and endometrial biopsy. Cytokine levels were measured in the uterine lavage and serum by quantifying inflammatory biomarkers. Immunohistochemistry staining was performed on the endometrial tissue to measure macrophage levels. Statistical analysis included a nonparametric analysis that compared medians of the marker levels before and after intrauterine device (IUD) insertion within the group and between the two groups. RESULTS: Sixteen participants completed the study: 5 solid organ transplant patients and 11 healthy patients. For the serum, there were no marked changes in the cytokines or soluble receptor levels in either group after IUD insertion. However, in the uterine lavage, there was an increase in cytokine levels post-IUD insertion for both healthy and transplant women. For the endometrial tissue, there was evidence of macrophage activity in both groups after device insertion. CONCLUSIONS: This pilot study investigated the uterine environment of the transplant patient population. Findings have pointed to the strong local inflammatory response following LNG-IUS insertion for the transplant recipients. In addition, these preliminary findings will help power a larger study that can investigate the safety and effectiveness of the IUD in this patient population. IMPLICATIONS: Findings from this pilot study suggest that the IUD is inducing a local inflammatory reaction in the uterus of the transplant patient as in the healthy control. A larger study can build on these preliminary results to pursue the efficacy and safety of IUD use among solid organ transplant patients. PMID- 27374736 TI - Assessing abortion coverage in nurse practitioner programs in Canada: a national survey of program directors. AB - OBJECTIVES: Although nurse practitioners (NPs) play a critical role in the delivery of reproductive health services in Canada, there is a paucity of published information regarding the reproductive health education provided in their training programs. Our study aimed to understand better the didactic and curricular coverage of abortion in Canadian NP programs. STUDY DESIGN: In 2014, we conducted a 3-contact, bilingual (English-French) mailed survey to assess the coverage of, time dedicated to and barriers to inclusion of 17 different areas of reproductive health, including abortion. We also asked respondents to speculate on whether or not mifepristone would be incorporated into the curriculum if approved by Health Canada for early abortion. We analyzed our results with descriptive statistics and used inductive techniques to analyze the open-ended questions for content and themes. RESULTS: Sixteen of 23 (70%) program directors or their designees returned our survey. In general, abortion-related topics received less coverage than contraception, ectopic pregnancy management and miscarriage management. Fifty-six percent of respondents reported that their program did not offer information about first-trimester abortion procedures and/or post-abortion care in the didactic curriculum. Respondents expressed interest in incorporating mifepristone/misoprostol into NP education and training. CONCLUSION: Reproductive health issues receive uneven and often inadequate curricular coverage in Canadian NP programs. Identifying avenues to expand education and training on abortion appears warranted. Embarking on curricular reform efforts is especially important given the upcoming introduction of mifepristone into the Canadian health system for early abortion. IMPLICATIONS: Our findings draw attention to the need to integrate abortion-related content into NP education and training programs. The approval of Mifegymiso(r) may provide a window of opportunity to engage in curriculum reform efforts across the health professions in Canada. PMID- 27374737 TI - Access to the copper IUD as post-coital contraception: results from a mystery caller study. AB - OBJECTIVE: To assess access to the copper IUD as post-coital contraception (PCC) and identify barriers to obtaining this contraceptive method. STUDY DESIGN: We used a "mystery caller" approach to survey primary care, family planning, and Ob/Gyn clinics in nine U.S. cities, identified via online search. A single researcher called 199 clinics, assuming the role of a patient seeking the copper IUD for PCC. Using a standard script, the researcher collected information regarding access to the copper IUD and respondent's knowledge of the copper IUD's indication for PCC. The primary outcome was availability of the copper IUD as PCC. Secondary outcomes included any provision of the copper IUD, awareness of the copper IUD's indication for use as PCC, and offering accurate information regarding the copper IUD as PCC. Fisher's exact test was used to compare outcomes by clinic type. RESULTS: Two thirds (68%) of primary care clinics, 87% of family planning clinics, and all Ob/Gyn clinics offered the copper IUD (p<.001). Only 11% of primary care clinics, however, were aware of the copper IUD's use as PCC, as compared with 63% of family planning clinics and 24% of Ob/Gyn clinics (p<.001). Few primary care or Ob/Gyn clinics offered the copper IUD as PCC, while 49% of family planning clinics did so (p<.001). CONCLUSION: Access to the copper IUD as PCC is limited and varies by clinic type. Knowledge gaps exist regarding the use of the copper IUD as PCC, as well as regarding the general medical guidelines for copper IUD placement. IMPLICATIONS: A majority of primary care and Ob/Gyn clinics do not offer the copper IUD as PCC, and only about half of family planning clinics do so. Barriers included lack of knowledge, unavailability of device, unavailability of an appointment with a trained provider, and outdated IUD provision protocols. PMID- 27374738 TI - Qualitative analysis of the role of self-weighing as a strategy of weight control for weight-loss maintainers in comparison with a normal, stable weight group. AB - Self-weighing seems to have a primary role in weight-loss maintenance. The use of this strategy may help correct even slight weight regain and contribute to long term weight stability. However, self-weighing has also been associated with negative psychological health consequences in specific subgroups. This study aimed to explore the use and the behavioral and psychological consequences of self-weighing in a group of weight-loss maintainers (WLoMs). We chose a qualitative design to conduct this investigation. Eighteen WLoMs were interviewed and compared to a matched comparison group of 18 participants with a lifelong normal stable weight (NSW). Analyses showed that most WLoMs needed regular self weighing to be aware of their weight. The weight displayed on the scale helped WLoMs sustain the continuous efforts needed to maintain weight loss and also at times triggered corrective actions that were sometimes drastic. Weight changes generated both negative and positive affect among WLoMs, who could experience anxiety because of self-weighing or have their self-esteem impaired in the case of weight gain. In comparison, the NSW group rarely used self-weighing. They relied on a conscious way of living to control their weight and needed fewer strategies. NSW participants simply went back to their routine when they felt a slight increase in their weight, without experiencing consequences on their mood or self-esteem. Regular self-weighing as a component of weight-loss maintenance should be encouraged to help WLoMs regulate their food and physical activity, provided that potential consequences on psychological well-being, including self esteem, are screened and addressed when needed. PMID- 27374739 TI - Role Models as Facilitators of Social Capital for Deaf Individuals: A Research Synthesis. AB - in a variety of contexts, deaf individuals often must navigate multiple societal, psychological, and physical barriers. It is frequently proposed that role models meet an important need for successful navigation in such contexts. The present article, a research synthesis, explores available literature on role models for deaf individuals, drawing from social capital theory to conceptualize how individuals in social networks can facilitate the development of resources necessary for navigating various settings. Four key themes were identified, two being that role models (a) address a critical need and (b) contribute to important developmental processes. In addition, (c) key elements appear to be necessary for effective role modeling, and (d) multidimensional cultural affiliations are important considerations within the role model process. Though more research is needed, the findings suggest that role models play an important role in how deaf individuals build social capital. PMID- 27374740 TI - Educational Programs for Deaf Students. PMID- 27374742 TI - Programs for Deaf-Blind Youth and Adults. PMID- 27374741 TI - University and College Programs for Personnel in Deafness. PMID- 27374743 TI - Advocacy, Support, and Rehabilitation Programs. PMID- 27374744 TI - Research on Deafness. PMID- 27374745 TI - Exploring non-hospital-related settings in Angola reveals new Acinetobacter reservoirs for blaOXA-23 and blaOXA-58. PMID- 27374746 TI - Routine atypical antibiotic coverage is not necessary in hospitalised patients with non-severe community-acquired pneumonia. PMID- 27374747 TI - Evaluation of a DNA microarray for rapid detection of the most prevalent extended spectrum beta-lactamases, plasmid-mediated cephalosporinases and carbapenemases in Enterobacteriaceae, Pseudomonas and Acinetobacter. AB - The dissemination of Gram-negative bacteria (GNB) producing extended-spectrum beta-lactamases (ESBLs), plasmid-encoded cephalosporinases (pAmpCs) and carbapenemases is a matter of great clinical concern. In this study, we evaluated a new low-density DNA array 'Check-MDR CT103 XL' (Check-Points, Wageningen, The Netherlands) that identifies the most clinically relevant beta-lactamase genes of ESBLs (blaTEM, blaSHV, blaCTX-M, blaBEL, blaPER, blaGES and blaVEB), pAmpCs (blaCMY-2-like, blaDHA, blaFOX, blaACC-1, blaACT/MIR and blaCMY-1-like/MOX) and carbapenemases (blaKPC, blaOXA-48, blaVIM, blaIMP, blaNDM, blaGIM, blaSPM and blaOXA-23, -24 and -58) in cultured bacteria. In total, 223 GNB isolates with well-characterised resistance mechanisms to beta-lactams were analysed. A specificity and sensitivity of 100% were recorded for most bla genes, with a slightly lower signal observed for blaIMP. The Check-MDR CT103 XL array proved highly accurate for the identification of epidemiologically relevant ESBL, pAmpC and carbapenemase genes harboured in Enterobacteriaceae, Pseudomonas and Acinetobacter spp. The Check-MDR CT103 XL assay is a significant improvement compared with Check-MDR CT103 and it highlights the ability of this array to evolve rapidly to adjust to the current needs for the detection of resistance mechanisms to beta-lactam agents. PMID- 27374748 TI - HCV1b genome evolution under selective pressure of the cyclophilin inhibitor alisporivir during the DEB-025-HCV-203 phase II clinical trial. AB - Major advances have revolutionized the HCV antiviral treatment field, with interferon-free combinations of direct-acting antivirals (DAAs) resulting into success rates of >90% for all HCV genotypes. Nevertheless, viral eradication at a global level stills remains challenging, stimulating the continued search for new affordable pan-genotypic drugs. To overcome selection of drug resistant variants, targeting host proteins can be an attractive mechanism of action. Alisporivir (Debio 025) is a potent pan-genotypic host-targeting antiviral agent, acting on cyclophilin A, which is necessary for HCV replication. The efficacy and safety of three different oral doses of alisporivir in combination with pegylated interferon-alpha2a given over a period of four weeks, was investigated in a randomized, double-blind and placebo-controlled phase IIa clinical trial, in 90 treatment-naive subjects infected with chronic hepatitis C, wherefrom 58 HCV1b samples were selected for genetic sequencing purposes. Sequencing results were used to study the HCV genome for amino acid changes potentially related with selective pressure and resistance to alisporivir. By comparing baseline and on treatment sequences, a large variation in proportion of amino acid changes was detected in all treatment arms. The NS5A variant D320E, which was previously identified during in vitro resistance selection and resulted in 3.6-fold reduced alisporivir susceptibility, emerged in two subjects in the alisporivir monotherapy arm. However, emergence of D320E appeared to be associated only with concurrent viral load rebound in one subject with 0.8log10IU/ml increase in HCV RNA. In general, for all datasets, low numbers of positions under positive selective pressure were observed, with no significant differences between naive and treated sequences. Additionally, incomplete sequence information for some of the 22 patients and the low number of individuals per treatment arm, is limiting the power to assess the association of alisporivir or interferon treatment with the observed amino acid changes. PMID- 27374749 TI - Small Molecule/Polymer Blend Organic Transistors with Hole Mobility Exceeding 13 cm(2) V(-1) s(-1). AB - A ternary organic semiconducting blend composed of a small-molecule, a conjugated polymer, and a molecular p-dopant is developed and used in solution-processed organic transistors with hole mobility exceeding 13 cm(2) V(-1) s(-1) (see the Figure). It is shown that key to this development is the incorporation of the p dopant and the formation of a vertically phase-separated film microstructure. PMID- 27374751 TI - Canine eosinophilic granuloma of the digits treated with prednisolone and chlorambucil. AB - BACKGROUND: Canine eosinophilic granuloma (CEG) is an uncommon disease. Lesions are typically located in the oral cavity and other cutaneous sites, but are rarely reported to affect the digits. The majority of cases are treated with prednisolone as a monotherapy; alternative treatment options include corticosteroids administered in combination with azathioprine, antihistamines, electrochemotherapy with bleomycin, and surgical resection. Neither chlorambucil nor laser previously have been reported as treatments. OBJECTIVES: To describe an alternative therapy for treatment of CEG; using chlorambucil in combination with prednisolone for those cases that fail to respond to prednisolone alone. The new treatment was chosen according to good clinical practice and after owner consent. ANIMALS: Two client owned dogs. METHODS: One case was initially treated with carbon dioxide laser to debulk the lesions. Both cases were treated with a combination of oral prednisolone and chlorambucil. RESULTS: Both dogs experienced rapid resolution of lesions with prednisolone and chlorambucil therapy. Case 1 remained in remission three months after withdrawing medication. Case 2 experienced relapse 10 weeks after discontinuing therapy but was well controlled on maintenance prednisolone with chlorambucil at low, well tolerated doses. CONCLUSIONS AND CLINICAL IMPORTANCE: Although CEG appears to be an uncommon disease, it should be included as a differential diagnosis for dermal, nodular lesions affecting the digits. Chlorambucil appears to be an effective and well tolerated prednisolone sparing agent for treatment of CEG. Carbon dioxide laser ablation appears to be an effective method of debulking CEGs. PMID- 27374750 TI - Early remodelling of the extracellular matrix proteins tenascin-C and phosphacan in retina and optic nerve of an experimental autoimmune glaucoma model. AB - Glaucoma is characterized by the loss of retinal ganglion cells (RGCs) and optic nerve fibres. Previous studies noted fewer RGCs after immunization with ocular antigens at 28 days. It is known that changes in extracellular matrix (ECM) components conduct retina and optic nerve degeneration. Here, we focused on the remodelling of tenascin-C and phosphacan/receptor protein tyrosine phosphatase beta/zeta in an autoimmune glaucoma model. Rats were immunized with optic nerve homogenate (ONA) or S100B protein (S100). Controls received sodium chloride (Co). After 14 days, no changes in RGC number were noted in all groups. An increase in GFAP mRNA expression was observed in the S100 group, whereas no alterations were noted via immunohistochemistry in both groups. Extracellular matrix remodelling was analyzed after 3, 7, 14 and 28 days. Tenascin-C and 473HD immunoreactivity in retinae and optic nerves was unaltered in both immunized groups at 3 days. At 7 days, tenascin-C staining increased in both tissues in the ONA group. Also, in the optic nerves of the S100 group, an intense tenascin-C staining could be shown. In the retina, an increased tenascin-C expression was also observed in ONA animals via Western blot. 473HD immunoreactivity was elevated in the ONA group in both tissues and in the S100 optic nerves at 7 days. At 14 days, tenascin-C and 473HD immunoreactivity was up-regulated in the ONA retinae, whereas phosphacan expression was up-regulated in both groups. We conclude that remodelling of tenascin-C and phosphacan occurred shortly after immunization, already before RGC loss. We assume that both ECM molecules represent early indicators of neurodegeneration. PMID- 27374752 TI - Soft magnetic memory of silk cocoon membrane. AB - Silk cocoon membrane (SCM), a solid matrix of protein fiber, responds to light, heat and moisture and converts these energies to electrical signals. Essentially it exhibits photo-electric and thermo-electric properties; making it a natural electro-magnetic sensor, which may influence the pupal development. This raises the question: 'is it only electricity?', or 'it also posses some kind of magnetic memory?' This work attempted to explore the magnetic memory of SCM and confirm its soft magnetism. Fe, Co, Ni, Mn, Gd were found in SCM, in traces, through energy dispersive X-ray analysis (EDX), X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma mass spectrometry (ICP-MS). Presence of iron was ascertained by electron paramagnetic resonance (EPR). In addition, EPR-spectra showed the presence of a stable pool of carbon-centric free radical in the cocoon structure. Carbon-centric free radicals behaves as a soft magnet inherently. Magnetic-Hysteresis (M-H) of SCM confirmed its soft magnetism. It can be concluded that the soft bio-magnetic feature of SCM is due to the entrapment of ferromagnetic elements in a stable pool of carbon centric radicals occurring on the super-coiled protein structure. Natural soft magnets like SCM provide us with models for developing eco-friendly, protein-based biological soft magnets. PMID- 27374753 TI - Randomized controlled trial of a messaging intervention to increase fruit and vegetable intake in adolescents: Affective versus instrumental messages. AB - OBJECTIVE: The present research aimed to test the efficacy of affective and instrumental text messages compared with a no-message control as a strategy to increase fruit and vegetable intake (FVI) in adolescents. DESIGN: A randomized controlled trial was used test impact of different text messages compared with no message on FVI over a 2-week period. METHOD: A total of 1,065 adolescents (14-19 years) from a high school of the South of Italy completed the baseline questionnaire and were randomly allocated to one of three conditions: instrumental messages (N = 238), affective messages (N = 300), and no messages (N = 521). Students in the message conditions received one message each day over a 2 week period. The messages targeted affective (affective benefits) or instrumental (instrumental benefits) information about FVI. Self-reported FVI at 2 weeks was the key dependent variable. Analyses were based on the N = 634 who completed all aspects of the study. RESULTS: Findings showed that messages significantly increased FVI, particularly in the affective condition and this effect was partially mediated by changes in affective attitude and intentions towards FVI. CONCLUSION: Text messages can be used to increase FVI in adolescents. Text messages based on affective benefits are more effective than text messages based on instrumental benefits. Statement of contribution What is already known on this subject? Text messages have been shown to promote positive change in health behaviours. However, the most appropriate target for such text messages is less clear although targeting attitudes may be effective. What does this study add? This randomized controlled study shows that text messages targeting instrumental or affective attitudes produce changes in fruit and vegetable intake (FVI) in adolescents. Text messages targeting affective attitudes are shown to be more effective than text messages targeting instrumental attitudes. The effect of affective text messages on FVI was partially mediated by changes in affective attitudes. PMID- 27374754 TI - Discrepancies between video head impulse and caloric tests in patients with enlarged vestibular aqueduct. AB - OBJECTIVE: We performed the video head impulse test (vHIT) and caloric test in patients with enlarged vestibular aqueducts (EVA). We compared the results with those found in Meniere's disease (MD) and acute vestibular neuritis to clarify the characteristics of vestibular dysfunction in EVA and to suggest reasons for the discrepancy between the vHIT and caloric tests in endolymphatic hydrops. STUDY DESIGN: Retrospective analysis. METHODS: Ten patients with EVA and confirmed biallelic SLC26A4 genetic mutations were enrolled. The results of video head impulse and caloric tests were analyzed and compared with those of patients diagnosed with MD (n = 76) or acute vestibular neuritis (n = 19). RESULTS: Among patients with EVA, 40% showed unilateral caloric weakness and 30% had recurrent episodes of vertigo. All patients with recurrent vertigo had caloric weakness. However, only 25% of patients with abnormal caloric test results had abnormal vHIT results. The discrepancy between the caloric test and vHIT results was also found in patients with MD, but not in patients with acute vestibular neuritis (abnormal vHIT results in 47.3% and 94.7% of patients with unilateral caloric weakness, respectively). CONCLUSION: Unilateral vestibular dysfunction was identified in 40% of patients with EVA by the caloric test, but caloric test results were not correlated with vHIT results. This finding was similar in patients with MD. Hence, it is possible that endolymphatic hydrops, a common pathologic feature of both EVA and MD, could cause the discrepancy, and that vestibulopathy in endolymphatic hydrops might be restricted to the low-frequency range. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:921-926, 2017. PMID- 27374755 TI - Complexities of Diagnosing Neuroleptic Malignant Syndrome in a Patient with Burn Injury: Could Stimulant Abuse be a Risk Factor? PMID- 27374756 TI - Sedentary behavior during school-time: Sociodemographic, weight status, physical education class, and school performance correlates in Brazilian schoolchildren. AB - OBJECTIVES: To investigate whether sedentary behavior during school-time is associated with gender, age, mother's education, having physical education classes, weight status, and academic performance. DESIGN: Cross-sectional study. METHODS: A sample of 571 children (7-12 years old) from five elementary schools in Florianopolis, South Brazil had their height and weight measured, and wore accelerometers during class time. Teachers completed a form to evaluate children's reading and writing skills. Parents provided sociodemographic and educational information. Data was analyzed using multilevel linear regression analyses. RESULTS: Children spent an average of 132min in sedentary behavior during school-time (64% of total school-time). Girls (137.5min), obese children (138.1min), older children (144.2min), and those who did not have physical education classes (140.2min) spent more time engaged in sedentary activities than their peers. Academic performance and mother's education were not associated with sedentary behaviors. CONCLUSIONS: Children spent most of their school-time in sedentary activities, with girls, older students, and obese students being even more sedentary than their peers. Physical education classes were a protective factor against excessive sedentary behavior in school. Interventions for reducing sedentary behavior during school-time could employ additional strategies to benefit the at risk groups. In addition, encouraging student's participation in physical education classes could minimize the time spent in sedentary behavior during school hours. PMID- 27374757 TI - Effects of aqueous extracts from Panax ginseng and Hippophae rhamnoides on acute alcohol intoxication: An experimental study using mouse model. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Acute alcohol intoxication (AAI) is a frequent emergency, but therapeutic drugs with superior efficacy and safety are lacking. Panax ginseng (PG) and Hippophae rhamnoides (HR) respectively has a wide application as a complementary therapeutic agent in China for the treatment of AAI and liver injury induced by alcohol. We investigated the effects of aqueous extracts from PG and HR (AEPH) on AAI mice and identified its underlying mechanisms. MATERIALS AND METHODS: Models of AAI were induced by intragastric administration of ethanol (8g/kg). Seventy-two Specific pathogen-free (SPF) male Kunming mice were randomly divided into six groups: normal group, positive control group, AEPH of low dosage (100mg/kg) group, AEPH of medium dose (200mg/kg) group, AEPH of high dosage (400mg/kg) group and model group. The mice were treated with metadoxine (MTD, 500mg/kg) and AEPH. Thirty minutes later, the normal group was given normal saline, while the other groups were given ethanol (i.g., 8g/kg). The impact of AEPH was observed. In the same way, another seventy two Kunming mice were randomly divided into six groups equally. The blood ethanol concentration at 0.5, 1, 1.5, 2, 3 and 6h after ethanol intake was determined by way of gas chromatography. The activity of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and microsomal ethanol oxidase (EO) in liver, and the concentration of beta-endorphin (beta-EP), leucine-enkephalin (LENK) in the brain were determined by enzyme-linked-immunosorbent serologic assay (ELISA). RESULTS: AEPH markedly prolonged alcohol tolerance time and shortened sober-up time after acute ethanol administration. AEPH decreased blood ethanol levels in six tests after ethanol intake. The 7-day survival rate of AEPH group was obviously superior to model group. AEPH increased the activities of ADH, ALDH, and decreased EO activity in liver. The crucial find was that AEPH markedly decreased beta-EP and LENK concentration in the brain. CONCLUSIONS: AEPH can markedly increase the levels of ADH, ALDH, decrease EO activity in liver and decrease the concentration of beta-EP and LENK in the brain to against acute alcohol intoxication in mice. PMID- 27374758 TI - Posterior urethral valves and vesicoureteral reflux: can prenatal ultrasonography distinguish between these two conditions in male fetuses? AB - OBJECTIVE: The objective of the study was to evaluate prenatal sonographic signs that distinguish male fetuses with posterior urethral valves (PUV) from those with vesicoureteral reflux (VUR). METHODS: Prenatal data were retrospectively retrieved from all consecutive women delivering between 2003 and 2012 of a male newborn with a postnatal diagnosis of PUV or VUR. Prenatal parameters included fetal bladder characteristics, identification of a dilated posterior urethra, and change in shape and size in the fetal renal pelvis or ureter. RESULTS: One hundred thirty-six women gave birth to a male newborn with a postnatal diagnosis of PUV (n = 49) or VUR (n = 87). The presence of posterior urethral dilatation [21 (42.9%) fetuses versus 0 (0%), p = 0.000], a thickened fetal bladder wall [37 (75.5%) vs 4 (4.6%), p = 0.000], and anhydramnios [14 (28.6%) vs 0, p = 0.000] were strongly associated with the postnatal diagnosis of PUV. Change in shape and size in the fetal renal pelvis or ureter was observed in 15 (17.2%) of 87 children with VUR versus 1 (2.0%) out of 49 with PUV (p = 0.010). CONCLUSIONS: Prenatal ultrasound may differentiate with reasonable accuracy male fetuses with a postnatal diagnosis of PUV from those with VUR. (c) 2016 John Wiley & Sons, Ltd. PMID- 27374759 TI - Maternal separation increases later immobility during forced swim in guinea pig pups: evidence for sensitization of a depressive-like state. AB - Early-life stress is thought to increase later vulnerability for developing depressive illness by sensitizing underlying stress-responsive systems. Guinea pig pups separated from their mother and isolated in a novel cage for 3 hr exhibit a sensitized depressive-like behavioral response when separated again the following day as well as weeks later. The behavioral response and its sensitization appear to be mediated by inflammatory factors. To determine if this sensitization is specific to the separation response or if it reflects a broader underlying depressive-like state, guinea pig pups that had either been separated for 3 hr or remained with their mothers were observed in the forced swim test the following 3 days. Earlier separation was found to increase the duration of immobility, a measure sensitive to antidepressant treatment. These results support the use of the guinea pig as a model for examining mechanisms of inflammatory-mediated sensitization of depression following stress in early life. PMID- 27374760 TI - Cortisol metabolism, postnatal depression and weight changes in the first 12 months postpartum. AB - BACKGROUND & OBJECTIVES: Postnatal depression correlates with postpartum weight retention, and dysregulated cortisol metabolism is evident in depressed individuals. Cortisol metabolism, BMI and metabolic phenotype are robustly associated, but the role of cortisol metabolism in postnatal mental health and weight loss has never been examined. DESIGN: A longitudinal observation. PATIENTS: Forty nine healthy women with uncomplicated pregnancy. MEASUREMENTS: BMI and urinary steroid metabolites at 1 week and 1, 3, 6 and 12 months postpartum. Validated urinary steroid metabolite ratios were measured to determine the activities of 11beta-hydroxysteroid dehydrogenases (11beta-HSD) that interconvert inactive cortisone and active cortisol and the 5alpha reductases that clear cortisol to its inactive metabolites. Postnatal depression symptoms were measured at 1, 6 and 12 months. RESULTS: Low 5alpha-reductase activity was associated with greater weight loss across the first year, independent of demographics, breastfeeding and depression. Postpartum BMI change was unrelated to postnatal depression at any time. Symptoms of postnatal depression were related to higher cortisol metabolite production at 12 months, independent of demographics and breastfeeding. CONCLUSIONS: Greatest weight loss in the postpartum year was associated with lower conversion of cortisone to cortisol and lower conversion of cortisol to its metabolites, supporting previous work that demonstrates the facilitative role of lower 5alpha-reductase and 11beta HSD-1 in weight loss. Greater depression symptoms were associated with higher cortisol metabolite production rates. Whilst weight and mental health are both associated with dysregulation of the HPA axis, there may be different pathways towards depressed and obese phenotypes in healthy postpartum samples. PMID- 27374761 TI - Retraction: 'Alendronate and vitamin D2 for prevention of hip fracture in Parkinson's disease: A randomized controlled trial,' by Sato, Y., Iwamoto, J., Kanoko, T., and Satoh, K. AB - The above article, published online on 14 March 2006 in Wiley Online Library (wileyonlinelibrary.com), and in Volume 21, Issue 7, Pages 924-929, has been retracted by agreement between the authors, the Editor-in-Chief, Jose A. Obeso, and Wiley Periodicals, Inc. The retraction has been agreed due to an acknowledgement from the authors that the co-authors did not participate in study design, data collection, data analysis, interpretation of data and drafting the manuscript. Thus all co-authors are honorary. Reference Sato, Y., Iwamoto, J., Kanoko, T., and Satoh, K. (2006) Alendronate and vitamin D2 for prevention of hip fracture in Parkinson's disease: A randomized controlled trial. Mov Disord. doi: 10.1002/mds.20825. PMID- 27374762 TI - Acute embryonic exposure to corticosterone alters physiology, behaviour and growth in nestlings of a wild passerine. AB - Maternally-derived glucocorticoids can modify the normal development of young animals. To date, little is known about maternal effects that are mediated by acute embryonic exposure to glucocorticoids. In birds, elevated maternal transmission of corticosterone (CORT) to egg albumen is mainly dependent on acute stress. In this study, we increased CORT levels in the egg albumen of a wild passerine, the great tit (Parus major), breeding in favourable deciduous and less suitable coniferous habitat. Subsequently we measured the somatic growth, baseline and acute glucocorticoid responses, immunity and behaviour of prenatally manipulated offspring with respect to control siblings. We found that prenatally CORT-exposed nestlings had lower baseline CORT levels, a more rapid decline in CORT during recovery from a standardized stressor, and a reduced heterophil/lymphocyte ratio compared with controls. Although stress-induced total CORT levels remained unchanged, free CORT levels were significantly lower and the levels of corticosteroid binding globulins (CBG) significantly higher in experimental offspring. Prenatally CORT-exposed offspring begged longer after hatching than controls. Stress-induced behavioural activity of fledglings did not differ between treatments, while its association with baseline CORT levels was significant in the control group only. The body mass and tarsus length of fledglings was positively affected by manipulation in unfavourable coniferous habitat only. We conclude that maternal effects related to elevated levels of albumen CORT modify diverse aspects of offspring phenotype and potentially increase offspring performance in resource poor environments. Moreover, our results indicate that maternal glucocorticoids may suppress the effect of hormones on behavioural responses. PMID- 27374763 TI - Mitochondrial function is altered in horse atypical myopathy. AB - Equine atypical myopathy in Europe is a fatal rhabdomyolysis syndrome that results from the ingestion of hypoglycin A contained in seeds and seedlings of Acer pseudoplatanus (sycamore maple). Acylcarnitine concentrations in serum and muscle OXPHOS capacity were determined in 15 atypical myopathy cases. All but one acylcarnitine were out of reference range and mitochondrial respiratory capacity was severely decreased up to 49% as compared to 10 healthy controls. The hallmark of atypical myopathy thus consists of a severe alteration in the energy metabolism including a severe impairment in muscle mitochondrial respiration that could contribute to its high death rate. PMID- 27374764 TI - 152 fs nanotube-mode-locked thulium-doped all-fiber laser. AB - Ultrafast fiber lasers with broad bandwidth and short pulse duration have a variety of applications, such as ultrafast time-resolved spectroscopy and supercontinuum generation. We report a simple and compact all-fiber thulium-doped femtosecond laser mode-locked by carbon nanotubes. The oscillator operates in slightly normal cavity dispersion at 0.055 ps(2), and delivers 152 fs pulses with 52.8 nm bandwidth and 0.19 nJ pulse energy. This is the shortest pulse duration and the widest spectral width demonstrated from Tm-doped all-fiber lasers based on 1 or 2 dimensional nanomaterials, underscoring their growing potential as versatile saturable absorber materials. PMID- 27374765 TI - Are Asian cultures really less ageist than Western ones? It depends on the questions asked. AB - Ageism is an increasing concern in ageing populations such as Asia and Europe. A prevalent assumption in psychology is that Eastern cultures may be less prone to ageism because of norms and values that honour and respect elders. Yet, evidence for this culture hypothesis is inconclusive. The current study examines this issue by comparing attitudes towards older people in an Eastern and Western samples of 184 young people from the UK and 249 from Taiwan. Attitudes to old age were measured both as meta-perceptions (the perceived normative context) and personal attitudes in regard to the cognitive, affective and behavioural components of ageism. Consistent with the culture hypothesis, meta-perceptions about competence and admiration were more positive in Taiwan than in the UK, yet other meta-perceptions were more negative pointing to the existence of old age subtypes. Personal attitudes about older people in regard to the affective and behavioural, but not the cognitive component, were more negative in Taiwan than in the UK. Thus, cultural differences in ageism are more nuanced than suggested by previous research. The importance of distinguishing between the normative context and personal attitudes as well as the different components of ageism is highlighted by the present findings. PMID- 27374766 TI - Integrated Electrowetting Nanoinjector for Single Cell Transfection. AB - Single cell transfection techniques are essential to understand the heterogeneity between cells. We have developed an integrated electrowetting nanoinjector (INENI) to transfect single cells. The high transfection efficiency, controlled dosage delivery and ease of INENI fabrication promote the widespread application of the INENI in cell transfection assays. PMID- 27374767 TI - Highly Selective Phosphinylphosphination of Alkenes with Tetraphenyldiphosphine Monoxide. AB - In sharp contrast to tetraphenyldiphosphine, which does not add to carbon-carbon double bonds efficiently, its monoxide, [Ph2 P(O)PPh2 ] can engage in a radical addition to various alkenes, thus affording the corresponding 1-phosphinyl-2 phosphinoalkanes regioselectively, and they can be converted into their sulfides by treatment with elemental sulfur. The phosphinylphosphination proceeds by the homolytic cleavage of the P(V) (O)-P(III) single bond of Ph2 P(O)PPh2 , followed by selective attack of the phosphinyl radical at the terminal position of the alkenes, and selective trapping of the resulting carbon radical by the phosphino group. Furthermore, the phosphinylphosphination product could be converted directly into its platinum complex with a hemilabile P,O chelation. PMID- 27374768 TI - Translation and validation of the Arabic version of generic medicines scale. AB - BACKGROUND: Generic drugs are considered the best alternative for the originator brand drugs because they have the same quality, safety, and efficacy yet offered at considerbaly lower cost. Prior research has developed instrumentation to assess patients' perceptions of generic drugs; however, little has been done to translate these measures in other languages. OBJECTIVES: This study's aim was to translate and validate an Arabic version of the generic drug scale (GMS) in a Jordanian sample. This was a cross-sectional study. METHODS: The English version of the GMS was translated to an Arabic version using the standard "forward backward" procedure of translation. The questionnaire was distributed to 225 patients. The translated version was then validated in a sample of patients. Face validity of the translated GMS was confirmed with pilot testing. Content validity of the translated GMS was evaluated by a number of pharmacists and academicians. Confirmatory factor analysis (CFA) was used to test a pre-specified relationship of observed measures. RESULTS: The GMS consisted of two subscales: efficacy, and similarity of generic drugs to originator brand drugs. The efficacy subscale consisted of ten items while the similarity subscale consisted of six. The responses to the items were framed on five-point, Likert-type scales. The instrument demonstrated good internal consistency (Cronbach's alpha = 0.83). The range model fit was good for some fit indices. The RMSEA value was 0.08, which indicates good fit. Also, CMIN/DF indicated a good fit model with a value of 2.7, as well as GFI and CFI values of 0.95 and 0.91, respectively. NFI and CFI values were 0.92 and 0.93, respectively. Factor loadings were over 0.30 for all items, which means the scale has CFA validity indictors. CONCLUSIONS: The Arabic version of GMS was proved to be a reliable and valid measure to investigate patients' belief regarding generic drugs as it showed acceptable, internal consistency reliability, face and content validity. PMID- 27374769 TI - Burden of treatment in the light of the international classification of functioning, disability and health: a "best fit" framework synthesis. AB - PURPOSE: This systematic literature review aimed to (1) summarize and explain the concept of Burden of Treatment (BoT) using the International Classification of Functioning, Disability and Health (ICF) terminology, and (2) inform the development of a future Comprehensive ICF Core Set for BoT. METHOD: Searches on EMbase, Medline, CINAHL and PsycINFO were conducted. Only qualitative studies were considered for inclusion. The screening and data extraction stages were followed by a "Best-fit" framework synthesis and content analysis, using the established ICF linking rules. Screening, data extraction, quality appraisal and data analysis were performed by two independent researchers. RESULTS: Seventeen studies were included in this review. The "Best-fit" framework synthesis generated 179 subthemes which identified that BoT impacts negatively on body functions and structures, restricts valued activities and participation and influences contextual factors through life roles, self-identify and relationships. The identified subthemes were linked to 77 ICF categories. CONCLUSIONS: This study is part of the preparatory phase of a Comprehensive ICF Core Set for BoT and our findings will inform the further needed studies on this phase. The use of ICF terminology to describe BoT provides an accessible route for understanding this complex concept, which is pivotal for rethinking clinical practice. Implications for rehabilitation Health professionals applying the ICF should consider the negative impact of interventions on patient's life roles and self-identity, body functions and structures and on valued activities and participation. Health professionals who may be concerned about the treatment burden being experienced by their patients can now use the ICF terminology to discuss this with the multidisciplinary team. Poor adherence to rehabilitation programs may be explained by an increased BoT. This phenomenon can now be mapped to the ICF, and coded using a framework well known by multidisciplinary teams. PMID- 27374771 TI - PADRE: Pedigree-Aware Distant-Relationship Estimation. AB - Accurate estimation of shared ancestry is an important component of many genetic studies; current prediction tools accurately estimate pairwise genetic relationships up to the ninth degree. Pedigree-aware distant-relationship estimation (PADRE) combines relationship likelihoods generated by estimation of recent shared ancestry (ERSA) with likelihoods from family networks reconstructed by pedigree reconstruction and identification of a maximum unrelated set (PRIMUS), improving the power to detect distant relationships between pedigrees. Using PADRE, we estimated relationships from simulated pedigrees and three extended pedigrees, correctly predicting 20% more fourth- through ninth-degree simulated relationships than when using ERSA alone. By leveraging pedigree information, PADRE can even identify genealogical relationships between individuals who are genetically unrelated. For example, although 95% of 13(th) degree relatives are genetically unrelated, in simulations, PADRE correctly predicted 50% of 13(th)-degree relationships to within one degree of relatedness. The improvement in prediction accuracy was consistent between simulated and actual pedigrees. We also applied PADRE to the HapMap3 CEU samples and report new cryptic relationships and validation of previously described relationships between families. PADRE greatly expands the range of relationships that can be estimated by using genetic data in pedigrees. PMID- 27374770 TI - Mutations in CDC45, Encoding an Essential Component of the Pre-initiation Complex, Cause Meier-Gorlin Syndrome and Craniosynostosis. AB - DNA replication precisely duplicates the genome to ensure stable inheritance of genetic information. Impaired licensing of origins of replication during the G1 phase of the cell cycle has been implicated in Meier-Gorlin syndrome (MGS), a disorder defined by the triad of short stature, microtia, and a/hypoplastic patellae. Biallelic partial loss-of-function mutations in multiple components of the pre-replication complex (preRC; ORC1, ORC4, ORC6, CDT1, or CDC6) as well as de novo stabilizing mutations in the licensing inhibitor, GMNN, cause MGS. Here we report the identification of mutations in CDC45 in 15 affected individuals from 12 families with MGS and/or craniosynostosis. CDC45 encodes a component of both the pre-initiation (preIC) and CMG helicase complexes, required for initiation of DNA replication origin firing and ongoing DNA synthesis during S phase itself, respectively, and hence is functionally distinct from previously identified MGS-associated genes. The phenotypes of affected individuals range from syndromic coronal craniosynostosis to severe growth restriction, fulfilling diagnostic criteria for Meier-Gorlin syndrome. All mutations identified were biallelic and included synonymous mutations altering splicing of physiological CDC45 transcripts, as well as amino acid substitutions expected to result in partial loss of function. Functionally, mutations reduce levels of full-length transcripts and protein in subject cells, consistent with partial loss of CDC45 function and a predicted limited rate of DNA replication and cell proliferation. Our findings therefore implicate the preIC as an additional protein complex involved in the etiology of MGS and connect the core cellular machinery of genome replication with growth, chondrogenesis, and cranial suture homeostasis. PMID- 27374772 TI - Identification and Functional Characterization of RSPO2 as a Susceptibility Gene for Ossification of the Posterior Longitudinal Ligament of the Spine. AB - Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common spinal disorder that results from ectopic ossification of the posterior longitudinal ligament and causes intractable myelopathy and radiculopathy. In a previous genome-wide association study (GWAS), we found six loci associated with OPLL; however, susceptibility genes in these loci have not been identified yet. Here, we examined one of the GWAS loci and identified RSPO2 (encoding R-spondin 2) as a susceptibility gene for OPLL. R-spondin 2 is a secreted agonist of canonical Wnt-beta-catenin signaling. RSPO2 was decreased in the early stage of chondrocyte differentiation. R-spondin 2 inhibited expression of genes encoding early chondrocyte differentiation markers by activating Wnt-beta-catenin signaling. rs374810, the most significantly associated SNP in the GWAS locus in chromosomal region 8q23.1 was located in the chondrocyte promoter region of RSPO2. A transcription factor, CCAAT-enhancer-binding protein beta (C/EBPbeta), specifically bound to the RSPO2 core promoter region containing rs374810 and increased RSPO2 expression. The risk allele of rs374810 affected the binding of the promoter with C/EBPbeta and decreased the RSPO2 transcription in vitro and in vivo. Our genetic and functional data indicate that RSPO2 is a susceptibility gene for OPLL. PMID- 27374773 TI - Mutations in Complex I Assembly Factor TMEM126B Result in Muscle Weakness and Isolated Complex I Deficiency. AB - Mitochondrial complex I deficiency results in a plethora of often severe clinical phenotypes manifesting in early childhood. Here, we report on three complex-I deficient adult subjects with relatively mild clinical symptoms, including isolated, progressive exercise-induced myalgia and exercise intolerance but with normal later development. Exome sequencing and targeted exome sequencing revealed compound-heterozygous mutations in TMEM126B, encoding a complex I assembly factor. Further biochemical analysis of subject fibroblasts revealed a severe complex I deficiency caused by defective assembly. Lentiviral complementation with the wild-type cDNA restored the complex I deficiency, demonstrating the pathogenic nature of these mutations. Further complexome analysis of one subject indicated that the complex I assembly defect occurred during assembly of its membrane module. Our results show that TMEM126B defects can lead to complex I deficiencies and, interestingly, that symptoms can occur only after exercise. PMID- 27374775 TI - Sugar Coating the Envelope: Glycoconjugates for Microbe-Host Crosstalk. AB - Tremendous progress has been made on mapping the mainly bacterial members of the human intestinal microbiota. Knowledge on what is out there, or rather what is inside, needs to be complemented with insight on how these bacteria interact with their biotic environment. Bacterial glycoconjugates, that is, the collection of all glycan-modified molecules, are ideal modulators of such interactions. Their enormous versatility and diversity results in a species-specific glycan barcode, providing a range of ligands for host interaction. Recent reports on the functional importance of glycosylation of important bacterial ligands in beneficial and pathogenic species underpin this. Glycoconjugates, and glycoproteins in particular, are an underappreciated, potentially crucial, factor in understanding bacteria-host interactions of old friends and foes. PMID- 27374774 TI - Biallelic Mutations in TMEM126B Cause Severe Complex I Deficiency with a Variable Clinical Phenotype. AB - Complex I deficiency is the most common biochemical phenotype observed in individuals with mitochondrial disease. With 44 structural subunits and over 10 assembly factors, it is unsurprising that complex I deficiency is associated with clinical and genetic heterogeneity. Massively parallel sequencing (MPS) technologies including custom, targeted gene panels or unbiased whole-exome sequencing (WES) are hugely powerful in identifying the underlying genetic defect in a clinical diagnostic setting, yet many individuals remain without a genetic diagnosis. These individuals might harbor mutations in poorly understood or uncharacterized genes, and their diagnosis relies upon characterization of these orphan genes. Complexome profiling recently identified TMEM126B as a component of the mitochondrial complex I assembly complex alongside proteins ACAD9, ECSIT, NDUFAF1, and TIMMDC1. Here, we describe the clinical, biochemical, and molecular findings in six cases of mitochondrial disease from four unrelated families affected by biallelic (c.635G>T [p.Gly212Val] and/or c.401delA [p.Asn134Ilefs(*)2]) TMEM126B variants. We provide functional evidence to support the pathogenicity of these TMEM126B variants, including evidence of founder effects for both variants, and establish defects within this gene as a cause of complex I deficiency in association with either pure myopathy in adulthood or, in one individual, a severe multisystem presentation (chronic renal failure and cardiomyopathy) in infancy. Functional experimentation including viral rescue and complexome profiling of subject cell lines has confirmed TMEM126B as the tenth complex I assembly factor associated with human disease and validates the importance of both genome-wide sequencing and proteomic approaches in characterizing disease-associated genes whose physiological roles have been previously undetermined. PMID- 27374776 TI - Assessment of drug-induced proarrhythmia: The importance of study design in the rabbit left ventricular wedge model. AB - In the present study, we investigated an impact of the stimulation rate on the detection of the proarrhythmic potential of 10 reference compounds with effects on different cardiac ion channels in the isolated arterially-perfused rabbit left ventricular wedge preparation. The compounds were tested in the wedge model using two distinct protocols; including baseline stimulation at 1-Hz followed by a brief period at 0.5-Hz, either without an additional brief period of 2-Hz stimulation (i.e. Protocol 1) or with 2-Hz stimulation (i.e. Protocol 2). As expected, QT-prolonging drugs (ibutilide and quinidine) prolonged the QT interval, similarly increased the Torsades de Pointes (TdP) score, and elicited early afterdepolarizations (EADs) in both protocols. HMR1556 and JNJ-303 (IKs blockers) also prolonged the QT interval up to 1MUM similarly in both protocols. Nifedipine (Ca(2+) antagonist) shortened the QT interval, and reduced force of contraction similarly in both protocols. However, Na(+) channel blockers (Ia, Ib, Ic) widened the QRS duration more in Protocol 2 than in Protocol 1. Furthermore, it was only possible to detect non-TdP-like ventricular tachycardia/fibrillation (VT/VF) induced by Na(+) blockers and by QT-shortening drugs (levcromakalim and mallotoxin) using the 2-Hz stimulation (Protocol 2). Our data suggest that the inclusion of a brief period of fast stimulation at 2Hz is critical for detecting drug-induced slowing of conduction (QRS widening), QT shortening and associated (non-TdP-like) VT/VF, which are distinct from the QT prolongation/TdP proarrhythmia in isolated, arterially-perfused rabbit left ventricular wedges. PMID- 27374778 TI - Subcranial craniofacial resection for advanced sinonasal malignant tumours involving the anterior skull base. AB - BACKGROUND: The subcranial approach is a modification of traditional craniofacial resection. It provides similar broad access to the anterior skull base, but with lower mortality and morbidity. It has been the surgical technique of choice at our institution since 2006 for treating advanced stage sinonasal tumours (American Joint Committee on Cancer stage III or above). This paper reports our experience and outcomes. METHOD AND RESULTS: Eighteen patients underwent subcranial craniofacial resection over a seven-year period, this being combined with a second adjunctive procedure in 89 per cent of cases. Forty per cent of patients required reconstruction of the primary defect. No peri-operative deaths occurred. One patient had a transient cerebrospinal fluid leak. The major complication rate was 33 per cent, of which 67 per cent were directly related to soft tissue reconstruction. Tumour recurrence rate was 17 per cent and the five year disease-free survival estimate was 40 per cent. CONCLUSION: The subcranial approach is a safe and effective technique that may be used to successfully treat advanced sinonasal malignancies with anterior skull base extension. PMID- 27374777 TI - Formation of Well-Defined, Functional Nanotubes via Osmotically Induced Shape Transformation of Biodegradable Polymersomes. AB - Polymersomes are robust, versatile nanostructures that can be tailored by varying the chemical structure of copolymeric building blocks, giving control over their size, shape, surface chemistry, and membrane permeability. In particular, the generation of nonspherical nanostructures has attracted much attention recently, as it has been demonstrated that shape affects function in a biomedical context. Until now, nonspherical polymersomes have only been constructed from nondegradable building blocks, hampering a detailed investigation of shape effects in nanomedicine for this category of nanostructures. Herein, we demonstrate the spontaneous elongation of spherical polymersomes comprising the biodegradable copolymer poly(ethylene glycol)-b-poly(d,l-lactide) into well defined nanotubes. The size of these tubes is osmotically controlled using dialysis, which makes them very easy to prepare. To confirm their utility for biomedical applications, we have demonstrated that, alongside drug loading, functional proteins can be tethered to the surface utilizing bio-orthogonal "click" chemistry. In this way the present findings establish a novel platform for the creation of biocompatible, high-aspect ratio nanoparticles for biomedical research. PMID- 27374779 TI - Ecological speciation in sympatric palms: 2. Pre- and post-zygotic isolation. AB - We evaluated reproductive isolation in two species of palms (Howea) that have evolved sympatrically on Lord Howe Island (LHI, Australia). We estimated the strength of some pre- and post-zygotic mechanisms in maintaining current species boundaries. We found that flowering time displacement between species is consistent across in and ex situ common gardens and is thus partly genetically determined. On LHI, pre-zygotic isolation due solely to flowering displacement was 97% for Howea belmoreana and 80% for H. forsteriana; this asymmetry results from H. forsteriana flowering earlier than H. belmoreana and being protandrous. As expected, only a few hybrids (here confirmed by genotyping) at both juvenile and adult stages could be detected in two sites on LHI, in which the two species grow intermingled (the Far Flats) or adjacently (Transit Hill). Yet, the distribution of hybrids was different between sites. At Transit Hill, we found no hybrid adult trees, but 13.5% of younger palms examined there were of late hybrid classes. In contrast, we found four hybrid adult trees, mostly of late hybrid classes, and only one juvenile F1 hybrid in the Far Flats. This pattern indicates that selection acts against hybrids between the juvenile and adult stages. An in situ reciprocal seed transplant between volcanic and calcareous soils also shows that early fitness components (up to 36 months) were affected by species and soil. These results are indicative of divergent selection in reproductive isolation, although it does not solely explain the current distribution of the two species on LHI. PMID- 27374780 TI - Radiology Perceptions and Preferences of Canadian Patients in an After-hours Acute Care Setting. PMID- 27374781 TI - ACR Appropriateness Criteria Fever Without Source or Unknown Origin-Child. AB - The cause of fever in a child can often be determined from history, physical examination, and laboratory tests; infections account for the majority of cases. Yet in 20%, no apparent cause can be found, designated as fever without source (FWS). The yield of chest radiography in children with FWS is low, and it is usually not appropriate. However, in children with respiratory signs, high fever (>39 degrees C), or marked leukocytosis (>=20,000/mm(3)), chest radiography is usually appropriate, as it has a higher yield in detecting clinically occult pneumonia. In newborns with FWS, there is higher risk for serious bacterial infection, and the routine use of chest radiography is controversial. In children with neutropenia, fever is a major concern. In some clinical circumstances, such as after hematopoietic stem cell transplantation, chest CT scan may be appropriate even if the results of chest radiography are negative or nonspecific, as it has higher sensitivity and can demonstrate specific findings (such as lung nodule and "halo sign") that can guide management. In a child with prolonged fever of unknown origin despite extensive medical workup (fever of unknown origin), diagnosis is usually dependent on clinical and laboratory studies, and imaging tests have low yield. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. PMID- 27374782 TI - Strain-modulated ferromagnetism and band gap of Mn doped Bi2Se3. AB - The quantized anomalous Hall effect (QAHE) have been theoretically predicted and experimentally confirmed in magnetic topological insulators (TI), but dissipative channels resulted by small-size band gap and weak ferromagnetism make QAHE be measured only at extremely low temperature (<0.1 K). Through density functional theory calculations, we systemically study of the magnetic properties and electronic structures of Mn doped Bi2Se3 with in-plane and out-of-plane strains. It is found that out-of-plane tensile strain not only improve ferromagnetism, but also enlarge Dirac-mass gap (up to 65.6 meV under 6% strain, which is higher than the thermal motion energy at room temperature ~26 meV) in the Mn doped Bi2Se3. Furthermore, the underlying mechanisms of these tunable properties are also discussed. This work provides a new route to realize high-temperature QAHE and paves the way towards novel quantum electronic device applications. PMID- 27374783 TI - PGMA-based gene carriers with lipid molecules. AB - Lipids, as the greatest constituent in cell membranes, have been widely used for biomedical applications because of their excellent biological properties. The introduction of membrane lipid molecules into gene vectors would embody greater biocompatibility, cellular uptake and transfection efficiency. In this work, one flexible strategy for readily conjugating lipid molecules with polycations was proposed based on atom transfer radical polymerization to produce a series of cholesterol (CHO)- and phosphatidylinositol (PI)-terminated ethanolamine functionalized poly(glycidyl methacrylate)s, namely CHO-PGEAs and PI-PGEAs, as effective gene carriers. CHO-PGEAs and PI-PGEAs truly demonstrated much better transfection performances compared to linear ethanolamine-functionalized poly(glycidyl methacrylate) (denoted as BUCT-PGEA) counterparts and traditional standard branched polythylenimine (PEI, 25 kDa). In addition, the good antitumor effects of CHO-PGEA and PI-PGEA were confirmed with suppressor tumor gene p53 systems in vitro and in vivo. The present work could provide a new strategy to develop effective cationic conjugation of lipid molecules for gene therapy. PMID- 27374784 TI - Concise Review: Current Status and Future Directions on Research Related to Nonalcoholic Fatty Liver Disease. AB - Considered a feature of the metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), is associated with insulin resistance, type 2 diabetes, obesity and drug toxicity. Its prevalence is estimated at about 30% in western countries mainly due to sedentary life styles and high fat diets. Genome-wide association studies have identified polymorphisms in several genes, for example, PNPLA3, and TM6SF2 which confer susceptibility to NAFLD. Here, we review recent findings in the NAFLD field with a particular focus on published transcriptomics datasets which we subject to a meta-analysis. We reveal a common gene signature correlating with the progression of the disease from steatosis and steatohepatitis and reveal that lipogenic and cholesterol metabolic pathways are main actors in this signature. We propose the use of disease-in-a-dish models based on hepatocyte-like cells derived from patient-specific induced pluripotent stem cells (iPSC). These will enable investigations into the contribution of genetic background in the progression from NALFD to non-alcoholic steatohepatitis. Furthermore, an iPSC based approach should aid in the elucidation of the function of new biomarkers, thus enabling better diagnostic tests and validation of potential drug targets. Stem Cells 2017;35:89-96. PMID- 27374785 TI - Gasotransmitter delivery via self-assembling peptides: Treating diseases with natural signaling gases. AB - Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) are powerful signaling molecules that play a variety of roles in mammalian biology. Collectively called gasotransmitters, these gases have wide-ranging therapeutic potential, but their clinical use is limited by their gaseous nature, extensive reactivity, short half-life, and systemic toxicity. Strategies for gasotransmitter delivery with control over the duration and location of release are therefore vital for developing effective therapies. An attractive strategy for gasotransmitter delivery is though injectable or implantable gels, which can ideally deliver their payload over a controllable duration and then degrade into benign metabolites. Self-assembling peptide-based gels are well-suited to this purpose due to their tunable mechanical properties, easy chemical modification, and inherent biodegradability. In this review we illustrate the biological roles of NO, CO, and H2S, discuss their therapeutic potential, and highlight recent efforts toward their controlled delivery with a focus on peptide-based delivery systems. PMID- 27374786 TI - Phenotypic expansion of TBX4 mutations to include acinar dysplasia of the lungs. AB - Mutations in the T-box transcription factor TBX4 gene have been reported in patients with Ischiocoxopodopatellar syndrome (MIM# 147891) and childhood-onset pulmonary arterial hypertension. Whole exome sequencing of DNA from a 1 day old deceased newborn, with severe diffuse developmental lung disorder exhibiting features of acinar dysplasia, and her unaffected parents identified a de novo TBX4 missense mutation p.E86Q (c.256G>C) in the DNA-binding T-box domain. We propose phenotypic expansion of the TBX4-related clinical disease spectrum to include acinar dysplasia of the lungs. The reported mutation is the first identified genetic variant causative for acinar dysplasia. (c) 2016 Wiley Periodicals, Inc. PMID- 27374787 TI - Generation of a Nonhuman Primate Model of Severe Combined Immunodeficiency Using Highly Efficient Genome Editing. AB - Recent advances in genome editing have facilitated the generation of nonhuman primate (NHP) models, with potential to unmask the complex biology of human disease not revealed by rodent models. However, their broader use is hindered by the challenges associated with generation of adult NHP models as well as the cost of their production. Here, we describe the generation of a marmoset model of severe combined immunodeficiency (SCID). This study optimized zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) to target interleukin-2 receptor subunit gamma (IL2RG) in pronuclear stage marmoset embryos. Nine of 21 neonates exhibited mutations in the IL2RG gene, concomitant with immunodeficiency, and three neonates have currently survived from 240 days to 1.8 years. Our approach demonstrates highly efficient production of founder NHP with SCID phenotypes, with promises of multiple pre-clinical and translational applications. PMID- 27374789 TI - Selling Stem Cells in the USA: Assessing the Direct-to-Consumer Industry. AB - Direct-to-consumer marketing of unapproved stem cell interventions is a well known phenomenon in countries with lax medical regulations. However, an examination of Internet-based marketing claims revealed widespread promotion of such interventions by businesses based in the United States. Such commercial activity suggests that regulatory agencies must better oversee this marketplace. PMID- 27374788 TI - Leukemic Stem Cells Evade Chemotherapy by Metabolic Adaptation to an Adipose Tissue Niche. AB - Adipose tissue (AT) has previously been identified as an extra-medullary reservoir for normal hematopoietic stem cells (HSCs) and may promote tumor development. Here, we show that a subpopulation of leukemic stem cells (LSCs) can utilize gonadal adipose tissue (GAT) as a niche to support their metabolism and evade chemotherapy. In a mouse model of blast crisis chronic myeloid leukemia (CML), adipose-resident LSCs exhibit a pro-inflammatory phenotype and induce lipolysis in GAT. GAT lipolysis fuels fatty acid oxidation in LSCs, especially within a subpopulation expressing the fatty acid transporter CD36. CD36(+) LSCs have unique metabolic properties, are strikingly enriched in AT, and are protected from chemotherapy by the GAT microenvironment. CD36 also marks a fraction of human blast crisis CML and acute myeloid leukemia (AML) cells with similar biological properties. These findings suggest striking interplay between leukemic cells and AT to create a unique microenvironment that supports the metabolic demands and survival of a distinct LSC subpopulation. PMID- 27374790 TI - Challenges and solutions for biofiltration of hydrophobic volatile organic compounds. AB - Volatile organic compounds (VOCs) emitted to the environment highly probably result in ecological and health risks. Many biotechnologies for waste gases containing hydrophobic VOCs have been developed in recent years. However, these biological processes usually exhibit poor removal performances for hydrophobic VOCs due to the low bioavailability. This review presents an overview of enhanced removal of hydrophobic VOCs in biofilters. Mechanisms and problems relevant to the biological removal of hydrophobic VOCs are reviewed, and then solutions including the addition of surfactants, application of fungal biocatalysts, biofiltration with pretreatment, innovative bioreactors and utilization of hydrophilic compounds are discussed in detail. Future research needs are also proposed. This review provides new insights into hydrophobic VOC removal by biofiltration. PMID- 27374791 TI - Quality and Value in an Evolving Health Care Landscape. AB - Demonstrating and improving value of care continues to be increasingly important in hand surgery. To prepare for emerging models that transition payment from volume to value, hand surgeons will benefit from a clear understanding of quality, cost, and value. National organizations and both public and private payers increasingly advocate for patient-reported outcome measures for pay for reporting and pay for performance initiatives. These are intended to incentivize providers and health systems to improve patient-centered care while minimizing costs. Appreciating the limitations to using patient-reported outcomes in hand surgery can ensure hand surgery is appropriately assessed in novel payment models. PMID- 27374792 TI - The Unifying Articular (Synovial) Origin for Intraneural Ganglion Cysts: Moving Beyond a Theory. PMID- 27374793 TI - Human CD39hi regulatory T cells present stronger stability and function under inflammatory conditions. AB - Autoimmune diseases are characterized by an imbalance between regulatory T cells and effector T-cell subsets, such as Th1 and Th17 cells. Studies have confirmed that natural CD4+Foxp3+ Tregs were unstable and dysfunctional in the presence of pro-inflammatory cytokines. In the current study, human CD39hi Tregs and CD39low Tregs were sorted from Tregs in vitro after 7 days of expansion. The functions of both Treg subsets were investigated under inflammatory conditions in vitro and in vivo. In the presence of IL-1beta and IL-6, cultured CD4+CD39hi Tregs maintained stable forkhead box protein 3 expression, whereas CD4+CD39low Tregs lost Foxp3 expression and trans-differentiated into Th1 or Th17 cells. Decreased IL-1betaR and IL-6R expression on the CD39hi Tregs was the primary mechanism responsible for Treg stability. In addition, reduced activation of downstream molecules, such as STAT1 and STAT3, through the modulation of CpG demethylation played an important role. Finally, human CD4+CD39hi Tregs but not CD4+CD39low Tregs protected against xenograft versus host disease in model mice. These results strongly implied the physiological importance of CD39 expression and suggested that manipulation of CD39hi Tregs might represent a novel strategy for the treatment of autoimmune diseases. PMID- 27374794 TI - BRD7 plays an anti-inflammatory role during early acute inflammation by inhibiting activation of the NF-kB signaling pathway. AB - Increasing evidence has shown a strong association between tumor-suppressor genes and inflammation. However, the role of BRD7 as a novel tumor suppressor in inflammation remains unknown. In this study, by observing BRD7 knockout mice for 6-12 months, we discovered that compared with BRD7+/+ mice, BRD7-/- mice were more prone to inflammation, such as external inflammation and abdominal abscess. By using mouse embryo fibroblast (MEF) cells from the BRD7 knockout mouse, an in vitro lipopolysaccharide (LPS)-stimulated MEF cell line was established. The mRNA levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), chemokine (C-X-C motif) ligand 1 (CXCL-1) and inducible nitric oxide synthase (iNOS) were significantly increased in BRD7-/- MEF cells compared with BRD7+/+ MEF cells after LPS stimulation for 1 or 6 h. In addition, the cytoplasm-to nucleus translocation of nuclear factor kappa-B (NF-kappaB; p65) and an increased NF-kappaB reporter activity were observed in BRD7-/- MEF cells at the 1 h time point but not at the 6 h time point. Furthermore, an in vivo dextran sodium sulfate (DSS)-induced acute colitis model was created. As expected, the disease activity index (DAI) value was significantly increased in the BRD7-/- mice after DSS treatment for 1-5 days, which was demonstrated by the presence of a significantly shorter colon, splenomegaly and tissue damage. Moreover, higher expression levels of IL-6, TNF-alpha, p65, CXCL-1 and iNOS, and an increased level of NF-kappaB (p65) nuclear translocation were also found in the DSS-treated BRD7-/- mice. These findings suggest that BRD7 has an anti-inflammatory role during early acute inflammation by inhibiting activation of the NF-kB signaling pathway, which provides evidence to aid in understanding the therapeutic effects of BRD7 on inflammatory diseases. PMID- 27374796 TI - Acrokeratoelastoidosis successfully treated with 10% salicylic acid ointment. PMID- 27374795 TI - Sam68 is a regulator of Toll-like receptor signaling. AB - Recognition of pathogens by Toll-like receptors (TLR) activate multiple signaling cascades and expression of genes tailored to mount a primary immune response, inflammation, cell survival and apoptosis. Although TLR-induced activation of pathways, such as nuclear factor kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPK), has been well studied, molecular entities controlling quantitative regulation of these pathways during an immune response remain poorly defined. We identified Sam68 as a novel regulator of TLR-induced NF-kappaB and MAPK activation. We found that TLR2 and TLR3 are totally dependent, whereas TLR4 is only partially dependent on Sam68 to induce the activation of NF-kappaB c-Rel. Absence of Sam68 greatly decreased TLR2- and TLR3-induced NF-kappaB p65 activation, whereas TLR4-induced p65 activation in a Sam68-independent manner. In contrast, Sam68 appeared to be a negative regulator of MAPK pathways because absence of Sam68 enhanced TLR2-induced activation of extracellular signal regulated kinases (ERK) and c-Jun N-terminal kinases (JNK). Interestingly, TLR2- and TLR3-induced gene expression showed a differential requirement of Sam68. Absence of Sam68 impaired TLR2-induced gene expression, suggesting that Sam68 has a critical role in myeloid differentiation primary response gene 88-dependent TLR2 signaling. TLR3-induced gene expression that utilize Toll/Interleukin-1 receptor-domain-containing adapter-inducing beta interferon pathway, depend only partially on Sam68. Our findings suggest that Sam68 may function as an immune rheostat that balances the activation of NF-kappaB p65 and c-Rel, as well as MAPK, revealing a potential novel target to manipulate TLR signaling. PMID- 27374797 TI - Expression of retinoid-related orphan receptor (ROR)gammat on NK22 cells in the peripheral blood and uterine endometrium of women with unexplained recurrent pregnancy loss and unexplained infertility. AB - AIM: Recently, NK22 cells, a subset of interleukin (IL)-22-producing natural killer (NK) cells, were identified. We have previously reported the higher percentage of NK22 cells in women suffering recurrent pregnancy loss (RPL). Moreover, we have also reported lower expression of NKp46, a kind of natural cytotoxicity receptor (NCR), on NK cells and the changes of NK cell producing cytokines in women who experience RPL. NK22 cells express NCRs, such as NKp44 or NKp46. Retinoid-related orphan receptor gammat (RORgammat) is known as a regulator of NK22 cells; however, in NK22 cells of peripheral blood (PB) and the uterine endometrium (UE), the relationship between NCRs and RORgammat is unclear. We investigate RORgammat expression NK22 cells in the PB and UE of women with unexplained infertility (uI) or unexplained RPL (uRPL). METHODS: Lymphocytes were extracted from PB and UE, derived from women with uI or uRPL. Expression of RORgammat and NCRs in NK cells and NK cell-produced cytokines were analyzed by flow cytometry. RESULTS: CD56+ /NKp46+ /RORgammat+ cells were positively correlated with CD56+ /IL-22+ cells in both PB and UE. CD56bright /NKp46bright /RORgammat+ cells were significantly higher in uRPL than in uI, and endometrial CD56bright /NKp46bright /RORgammat+ cells were positively correlated with PB. In UE, CD56bright /RORgammat+ cells were negatively correlated with CD56bright /interferon-gamma+ and CD56bright /tumor necrosis factor-alpha+ cells of uRPL. CONCLUSION: RORgammat may be associated with NK22 cells in reproduction. Particularly, higher expression of RORgammat may be associated with elevated NK22 cells in uRPL. PMID- 27374798 TI - The role of endoscopy in the management of suspected small-bowel bleeding. PMID- 27374799 TI - T-Cell Abnormalities in Common Variable Immunodeficiency. AB - Common variable immunodeficiency (CVID) is the most common clinical primary immunodeficiency. It is characterized by a defect in B-cell differentiation to plasma and memory B cells. Moreover, numerous T-cell abnormalities have been reported and include decreased T-cell count and proliferative response, increased T-cell activation and apoptosis, and abnormalities in cytokine production. The aims of this review are to describe phenotypic and functional defects in T cells in CVID patients and to review the literature with respect to the effects of immunoglobulin replacement on the T-cell component in CVID patients. PMID- 27374800 TI - Hymenobacter glacieicola sp. nov., isolated from glacier ice. AB - A Gram-stain-negative, rod-shaped, non-motile and red-pink-pigmented bacterial strain, designated B1909T, was isolated from an ice core drilled from Muztagh Glacier on the Tibetan Plateau, China. A phylogenetic tree based on 16S rRNA gene sequences showed that strain B1909T formed a lineage within the genus Hymenobacter and was closely related to Hymenobacter xinjiangensis X2-1gT (96.16 % similarity) and Hymenobacter psychrotolerans Tibet-IIU11T (95.99 %). The predominant fatty acids were iso-C15 : 0, summed feature 3 (C16 : 1omega7c/C16 : 1omega6c), summed feature 4 (iso-C17 : 1omega6c I/anteiso B), C16 : 1omega5c, anteiso-C15 : 0 and iso-C17 : 0 3-OH. The major menaquinone was MK-7. The major polar lipid was phosphatidylethanolamine. The DNA G+C content was 59 mol%. On the basis of the phenotypic, phylogenetic and chemotaxonomic data presented, strain B1909T is considered to represent a novel species of the genus Hymenobacter, for which the name Hymenobacterglacieicola sp. nov. is proposed; the type strain is B1909T (=JCM 30596T=CGMCC 1.12990T). PMID- 27374804 TI - Antimicrobial properties of cultivable bacteria associated with seaweeds in the Gulf of Mannar on the southeast coast of India. AB - In this study, 234 bacterial strains were isolated from 7 seaweed species in the Gulf of Mannar on the southeast coast of India. The strains having consistent antimicrobial activity were chosen for further studies, and this constituted about 9.8% of the active strains isolated. Phylogenetic analysis using 16S rDNA sequencing with the help of classical biochemical identification indicated the existence of 2 major phyla, Firmicutes and Proteobacteria. Antimicrobial activity analysis combined with the results of amplifying genes encoding for polyketide synthetase and nonribosomal peptide synthetase showed that seaweed-associated bacteria had broad-spectrum antimicrobial activity. These epibionts might be beneficial to seaweeds by limiting or preventing the development of competing or fouling bacteria. Phylogenetic analysis of ketosynthase (KS) regions with respect to the diverse range of KS domains showed that the KS domains from the candidate isolates were of Type I. The bacterial cultures retained their antimicrobial activities after plasmid curing, which further suggested that the antimicrobial activity of these isolates was not encoded by plasmid, and the genes encoding the antimicrobial product might be present within the genome. Seaweed-associated bacteria with potential antimicrobial activity suggested that the seaweed species are an ideal ecological niche harboring specific bacterial diversity representing a largely underexplored source of antimicrobial secondary metabolites. PMID- 27374805 TI - Evaluation of a German version of the Strengthening Families Programme 10-14: a randomised controlled trial. AB - BACKGROUND: The purpose of this study is to evaluate the effects of a German adaptation of the Strengthening Families Programme 10-14 (SFP 10-14; Familien Starken). METHODS: A multi-centre randomised controlled trial comparing the German SFP version consisting of seven sessions and four booster-sessions with a minimal intervention on parenting as control condition. Outcomes comprise measures of adolescent substance use (initiation) and behaviour problems and are assessed at baseline, after programme delivery and at 6- and 18-month follow-ups. Primary outcomes were lifetime tobacco, alcohol and cannabis use at 18 months. Data of n = 292 families were analysed using baseline adjusted logistic regressions and mixed models. RESULTS: We observed reduced rates of lifetime tobacco use in analyses with follow-up respondents, but not in data using the complete intention to treat sample with multiple imputation estimates for missing data. Parents reported fewer adolescent behaviour problems in analyses with the total sample and multiple imputed data, but not in data with follow-up respondents only. There were no other significant effects of SFP 10-14. CONCLUSION: Overall the medium size effects found in previous US trials could not be replicated in a German context. PMID- 27374806 TI - Health Care Decision Making for Reproductive Care. PMID- 27374807 TI - Insurance Coverage for Contraceptives. PMID- 27374802 TI - Plasmodium species: master renovators of their host cells. AB - Plasmodium parasites, the causative agents of malaria, have developed elaborate strategies that they use to survive and thrive within different intracellular environments. During the blood stage of infection, the parasite is a master renovator of its erythrocyte host cell, and the changes in cell morphology and function that are induced by the parasite promote survival and contribute to the pathogenesis of severe malaria. In this Review, we discuss how Plasmodium parasites use the protein trafficking motif Plasmodium export element (PEXEL), protease-mediated polypeptide processing, a novel translocon termed the Plasmodium translocon of exported proteins (PTEX) and exomembranous structures to export hundreds of proteins to discrete subcellular locations in the host erythrocytes, which enables the parasite to gain access to vital nutrients and to evade the immune defence mechanisms of the host. PMID- 27374809 TI - [Disease Models] [Neuroscience, Behavior] [Genetics, Breeding, Gene Functions, Bio-Resources] [Management, Ethics, Welfare] [International Presentation] [Anatomy, Histology, Pathology] [Reproduction Strain Development] [International Awards] [Microbiology, Infection, Immunity] [Microbiology, Infection, Immunity] [Primates (Methodology, Biochemistry)] [Embryo Manipulation, Regenerative Medicine]. PMID- 27374808 TI - High-fiber and high-protein diets shape different gut microbial communities, which ecologically behave similarly under stress conditions, as shown in a gastrointestinal simulator. AB - The aim of this work was to investigate the relationship between the structure of gut microbial communities fed with different diets (i.e. high-protein-HP- versus high-fiber-HF-diet) and their functional stability when challenged with mild and acute doses of a mix of amoxicillin, ciprofloxacin, and tetracycline. We made use of the Simulator of the Human Intestinal Microbial Ecosystem (SHIME(r))-a continuous model of the gastrointestinal tract-coupled with 16S-targeted Illumina and metabolomics (i.e. UHPLC-HRMS) analyses. Independently of the diet, the sudden exposure to an acute stress led to a modification of the microbial community structure, selecting for species belonging to Bacillus spp.; Clostridium cluster XIVa; Enterococci; Bacteroides; and Enterobacteriaceae. The antibiotic treatment led to a decrease in the number of operational taxonomic units (at least -10%). Cluster analysis of untargeted metabolic data showed that the antibiotic treatment affected the microbial activity. The impact on metabolites production was lower when the community was preexposed to mild doses of the antibiotic mix. This effect was stronger in the proximal colon for the HF diet and in the distal colon for the HP diet. Different diets shaped different gut microbial communities, which ecologically behaved similarly under stress conditions. PMID- 27374810 TI - [Management, Ethics, Welfare] [Microbiology, Infection, Immunity] [Disease Models] [Bio-Resources] [Methodology, Replacement, Refinement] [Senescence] [Neuroscience, Behavior] [Reproduction] [Embryo Manipulation, Regenerative Medicine] [Genetics, Breeding, Gene Functions]. PMID- 27374811 TI - Primary umbilical endometriosis (PUE). AB - Primary endometriosis of the umbilicus, Villars nodule, rarely occurs. It is characterized by a discolored change in the umbilicus which manifests itself with cyclic menstrual-related symptoms such as pain, swelling and bleeding. Often the diagnosis is based on objective findings, but imaging and histology predicts and verify the diagnosis. Radical excision is performed with good results. We present ten cases with primary umbilical endometriosis and present the referral pattern dominated by primary referral to the gastro-surgeon reflecting difficulties in finding the right diagnosis. PMID- 27374812 TI - The role of side chain entropy and mutual information for improving the de novo design of Kemp eliminases KE07 and KE70. AB - Side chain entropy and mutual entropy information between residue pairs have been calculated for two de novo designed Kemp eliminase enzymes, KE07 and KE70, and for their most improved versions at the end of laboratory directed evolution (LDE). We find that entropy, not just enthalpy, helped to destabilize the preference for the reactant state complex of the designed enzyme as well as favoring stabilization of the transition state complex for the best LDE enzymes. Furthermore, residues with the highest side chain couplings as measured by mutual information, when experimentally mutated, were found to diminish or annihilate catalytic activity, some of which were far from the active site. In summary, our findings demonstrate how side chain fluctuations and their coupling can be an important design feature for de novo enzymes, and furthermore could be utilized in the computational steps in lieu of or in addition to the LDE steps in future enzyme design projects. PMID- 27374813 TI - How to Avoid Lymphatic Wound Complications After Vascular Groin Surgery. PMID- 27374814 TI - Late Survival in Nonoperated Patients with Infrarenal Abdominal Aortic Aneurysm. AB - OBJECTIVE/BACKGROUND: Historical studies report high rupture rates in patients with nonoperated abdominal aortic aneurysms (AAAs) of > 5.5 cm diameter, although a recent audit has questioned this. METHODS: This was a retrospective review of 138/764 (18%) patients with AAAs evaluated in a preassessment anaesthetic clinic (PAC) between 2006 and 2012, who either did not undergo elective AAA repair or who underwent deferred repair. The remaining 626 underwent repair. Patients with severe comorbidities (dementia, advanced malignancy, life-expectancy < 1 year) and not referred to PAC were excluded. RESULTS: At a median of 27 months, 71 (52%) died, 36 (51%) following rupture. Cumulative survival, free from rupture or surgery for acute symptoms, was 96% at 1 year, 84% at 3 years, and 64% at 5 years, where baseline AAA diameters were 5.5-6.9 cm. For diameters >= 7 cm, survival, free from rupture, was 65% at 1 year, 29% at 3 years, and 0% at 5 years. Median interval to rupture was 47 months (AAA diameter 5.5-6.9 cm) and 21 months where baseline diameters were >= 7 cm. Rupture accounted for 32% of late deaths in patients with AAAs of 5.5-5.9 cm diameter, 46% in those with AAAs measuring 6.0-6.9 cm in diameter, and 71% in patients with AAA measuring >= 7 cm in diameter. CONCLUSION: Approximately half of all late deaths in this nonoperated cohort were not AAA related, suggesting that even had repair been undertaken, it would not have prolonged patient survival. The incidence of rupture in "high-risk" patients with an AAA < 7 cm diameter was < 5% at 1 year, thereby giving ample time to optimise risk factors and improve pre-existing medical conditions prior to undertaking a deferred intervention. Even if these patients did not undergo surgical repair, the risk of late rupture was relatively low. By contrast, nonoperated patients with AAAs >= 7 cm in diameter face a very high risk of rupture and will probably benefit from elective surgery, with the caveat that a higher procedural risk might have to be incurred. PMID- 27374815 TI - Are We Ready for Routine 'Subclinical' Atherosclerosis Screening? Not Yet.... PMID- 27374816 TI - Energetics, barriers and vibrational spectra of partially and fully hydrogenated hexagonal boron nitride. AB - We study hydrogen chemisorption at full coverage and low concentrations on hexagonal boron nitride (h-BN). Chemisorption trends reveal the complex nature of hydrogenation. Barriers for diffusion are found to be significantly altered by the presence of additional H atoms. Moreover, the presence of a Stone-Wales defect may dramatically enhance the bond strength of H to the h-BN surface. These findings provide new insights to understand and characterize hydrogenated boron nitride. PMID- 27374817 TI - DNA hypomethylation of CD133 promoter is associated with recurrent glioma. AB - Gliomas are the most common type of brain tumor in the central nervous system of adults, and are highly aggressive, resistant to treatment, and prone to recurrence. Brain tumor stem cells (BTSCs) are implicated in tumor initiation and recurrence. Cluster of differentiation (CD)133 is currently the most widely used BTSC marker; however, its role in glioma development and progression is largely unknown. In this study, we evaluated CD133 expression in pairs of primary and recurrent human glioma specimens from 24 patients. We found that recurrent gliomas have aberrantly upregulated CD133 levels. To clarify the mechanism underlying this observation, we assessed CD133 promoter (P)2 methylation status by bisulfite sequencing and found that P2 hypomethylation was associated with the increase in CD133 expression and glioma recurrence. These results suggest that CD133 overexpression in BTSCs due to P2 hypomethylation underlies glioma recurrence, which may provide insight into the mechanism of glioma recurrence and provide a basis for novel therapies for glioma treatment. PMID- 27374818 TI - Long-term Stability of Autotransplanted Premolars as a Substitute for Molars in Adults. AB - Autotransplantation is a viable treatment option for tooth replacement when a suitable donor tooth is available. This case report presents 2 cases that describe successful treatment outcome and prognosis after autotransplantation of a mature premolar as a missing molar. The first premolar was extracted for orthodontic purposes and transplanted to the missing first molar site in the mandible. The transplanted tooth was monitored up to 7 years. The transplant was functional and maintained a normal bone level throughout the follow-up period. Clinical examination showed normal physiologic movement without any signs of ankylosis and root resorption. Autotransplantation of a mature premolar to a molar site is a viable treatment option showing successful results. The selection of a functional donor tooth, adequate surgical procedures, and timely application of orthodontic movement may have positively contributed to the favorable prognosis. PMID- 27374819 TI - Regulatory role of microRNAs in the proliferation and differentiation of adipose derived stem cells. AB - Adipose-derived stem cells (ASCs) are multipotent mesenchymal stem cells obtained from stromal-vascular fraction of adipose tissue. ASCs are a promising resource for cell therapy due to their simple isolation, extensive expansion potential, and low immunogenicity. ASCs repair and regenerate damaged tissue by direct differentiation, whereas many other approaches rely on the secretion of paracrine factors. miRNAs target mRNAs for cleavage or translational repression, and have been shown to play critical roles in the regulation of stem cell proliferation and differentiation. The miRNA expression profile of ASCs varies according to the isolation and culturing method, and more than 40 different miRNAs have been reported to regulate ASC proliferation and differentiation. Therefore, this review summarizes the ASC-related miRNAs and their pivotal roles in regulating the proliferation and differentiation of ASCs. A comprehensive understanding of the effects of miRNAs on the proliferation and differentiation of ASCs is important and useful to enhance the regenerative potential of ASCs. PMID- 27374821 TI - Ischemic stroke - the challenge continues. PMID- 27374820 TI - Binge Drinking Decreases Corticotropin-Releasing Factor-Binding Protein Expression in the Medial Prefrontal Cortex of Mice. AB - BACKGROUND: Dysregulation of the corticotropin-releasing factor (CRF) system has been observed in rodent models of binge drinking, with a large focus on CRF receptor 1 (CRF-R1). The role of CRF-binding protein (CRF-BP), a key regulator of CRF activity, in binge drinking is less well understood. In humans, single nucleotide polymorphisms in CRHBP are associated with alcohol use disorder and stress-induced alcohol craving, suggesting a role for CRF-BP in vulnerability to alcohol addiction. METHODS: The role and regulation of CRF-BP in binge drinking were examined in mice exposed to the drinking in the dark (DID) paradigm. Using in situ hybridization, the regulation of CRF-BP, CRF-R1, and CRF mRNA expression was determined in the stress and reward systems of C57BL/6J mice after repeated cycles of DID. To determine the functional role of CRF-BP in binge drinking, CRF BP knockout (CRF-BP KO) mice were exposed to 6 cycles of DID, during which alcohol consumption was measured and compared to wild-type mice. RESULTS: CRF-BP mRNA expression was significantly decreased in the prelimbic (PL) and infralimbic medial prefrontal cortex (mPFC) of C57BL/6J mice after 3 cycles and in the PL mPFC after 6 cycles of DID. No significant changes in CRF or CRF-R1 mRNA levels were observed in mPFC, ventral tegmental area, bed nucleus of the stria terminalis, or amygdala after 3 cycles of DID. CRF-BP KO mice do not show significant alterations in drinking compared to wild-type mice across 6 cycles of DID. CONCLUSIONS: These results reveal that repeated cycles of binge drinking alter CRF-BP mRNA expression in the mPFC, a region responsible for executive function and regulation of emotion and behavior, including responses to stress. We observed a persistent decrease in CRF-BP mRNA expression in the mPFC after 3 and 6 DID cycles, which may allow for increased CRF signaling at CRF-R1 and contribute to excessive binge-like ethanol consumption. PMID- 27374822 TI - Nobel Peace Prize nomination for Doctors Against Forced Organ Harvesting (DAFOH) a recognition of upholding ethical practices in medicine. PMID- 27374823 TI - New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain. AB - The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. The mechanisms and mediators (eg, nitric oxide, astrocytes, and ion channels) that regulate CBF-metabolism coupling have been extensively studied. The neurovascular unit is a conceptual model encompassing the anatomical and metabolic interactions between the neurons, vascular components, and glial cells in the brain. It is compromised under disease states such as stroke, diabetes, hypertension, dementias, and with aging, all of which trigger a cascade of inflammatory responses that exacerbate brain damage. Hence, tight regulation and maintenance of neurovascular coupling is central for brain homeostasis. This review article also discusses the waste clearance pathways in the brain such as the glymphatic system. The glymphatic system is a functional waste clearance pathway that removes metabolic wastes and neurotoxins from the brain along paravascular channels. Disruption of the glymphatic system burdens the brain with accumulating waste and has been reported in aging as well as several neurological diseases. PMID- 27374824 TI - High frequency of cutaneous manifestations including vitiligo and alopecia areata in a prospective cohort of patients with chronic graft-vs-host disease. AB - AIM: To determine the frequency and the characteristics of cutaneous manifestations, especially vitiligo and alopecia areata, in patients with chronic graft-vs-host disease (cGVHD). METHODS: 50 patients with cGVHD were prospectively enrolled in the observational study protocol and evaluated by an experienced dermatologist. The evaluation was focused on the clinical spectrum of skin and adnexal involvement, and the cutaneous GVHD score was determined according to National Institutes of Health (NIH) Consensus criteria. The presence of vitiligo, alopecia, xerosis, nail changes, and dyspigmentation was also assessed. RESULTS: Out of 50 cGVHD patients, 28 (56%) had skin involvement, and 27 of them (96%) had hypo and/or hyperpigmentations. 11 patients (39%) had a mild cutaneous NIH cGVHD score, 22% moderate, and 39% severe. 15 (30%) patients had nail changes and 10 (20%) had vitiligo or alopecia areata. Univariate analysis showed that patients with vitiligo/alopecia areata received more lines of prior systemic immunosuppressive therapy (P=0.043), had lower Karnofsky performance status (P=0.028), and had a higher B-cell number (P=0.005), platelet count (P=0.022), and total protein (P=0.024). Vitiligo and alopecia areata were associated with higher NIH skin score (P=0.001), higher intensity of immunosuppressive treatment (P=0.020), and total body irradiation conditioning (P=0.040). Multivariate regression model showed that patients with higher NIH skin scoring were 3.67 times more likely to have alopecia and/or vitiligo (odds ratio 3.67; 95% confidence interval 1.26-10.73), controlled for all other factors in the model (age at study entry, number of B-cells, platelet count, and global NIH score). CONCLUSION: These data indicate that vitiligo and alopecia areata occur more frequently in cGVHD than previously reported. PMID- 27374825 TI - Glycoprotein YKL-40: a novel biomarker of chronic graft-vs-host disease activity and severity? AB - AIM: To investigate whether increased YKL-40 levels positively correlate with graft-vs-host disease (cGVHD) activity and severity and if YKL-40 could serve as a disease biomarker. METHODS: This case-control study was conducted at the University Hospital Centre Zagreb from July 2013 to October 2015. 56 patients treated with hematopoietic stem cell transplantation (HSCT) were included: 35 patients with cGVHD and 21 without cGVHD. There was no difference between groups in age, sex, median time from transplant to study enrollment, intensity of conditioning, type of donor, or source of stem cells. Blood samples were collected at study enrollment and YKL-40 levels were measured with ELISA. Disease activity was estimated using Clinician's Impression of Activity and Intensity of Immunosuppression scales and disease severity using Global National Institutes of Health (NIH) score. RESULTS: YKL-40 levels were significantly higher in cGVHD patients than in controls (P=0.003). The difference remained significant when patients with myelofibrosis were excluded from the analysis (P=0.017). YKL-40 level significantly positively correlated with disease severity (P<0.001; correlation coefficient 0.455), and activity estimated using Clinician's Impression of Activity (P=0.016; correlation coefficient 0.412) but not using Intensity of Immunosuppression (P=0.085; correlation coefficient 0.296). CONCLUSION: YKL-40 could be considered a biomarker of cGVHD severity and activity. However, validation in a larger group of patients is warranted, as well as longitudinal testing of YKL-40 levels in patients at risk of developing cGVHD. PMID- 27374826 TI - Imatinib and dasatinib as salvage therapy for sclerotic chronic graft-vs-host disease. AB - AIM: To assess the toxicity, tolerance, steroid-sparing capacity, effectiveness, and response rate to imatinib and dasatinib for the treatment of severe sclerotic chronic graft-vs-host disease (scGVHD). METHODS: This retrospective study analyzed 8 consecutive patients with severe refractory scGVHD who received salvage therapy with imatinib. Patients intolerant and/or refractory to imatinib received dasatinib treatment. RESULTS: 7 patients discontinued imatinib treatment (1 achieved complete response, 5 were resistant and/or intolerant, and 1 developed grade IV neutropenia) and 1 patient achieved prolonged partial response, but died due to an infectious complication while on treatment. 5 patients started dasatinib treatment (3 achieved partial responses and discontinued dasatinib, 1 achieved a durable partial response, but died due to a consecutive rapid pulmonary cGVHD progression and 1 with stable disease discontinued treatment due to gastroenteric intolerance). The response rate (partial and/or complete responses) for severe scGVHD was 25% for imatinib and 60% for dasatinib. CONCLUSION: In our series, dasatinib was better tolerated, safer, steroid-sparing, and had a low incidence of infectious complications, which suggests that it may be a more effective therapeutic alternative for patients with refractory scGVHD than imatinib. Treatment of scGVHD with effective antifibrotic drugs such as TKI, which block the kinase fibrotic pathway, may be a safe and effective therapeutic option, but further studies are needed to confirm our findings. PMID- 27374827 TI - Adiponectin and resistin in acute and chronic graft-vs-host disease patients undergoing allogeneic hematopoietic stem cell transplantation. AB - AIM: To investigate the association of adiponectin and resistin levels in patients undergoing hematopoietic stem cell transplantation (HSCT) with the clinical outcome, including the occurrence of acute and chronic graft-vs-host disease (GVHD), non-relapse mortality, and overall survival. METHODS: We prospectively collected serum samples from 40 patients undergoing either autologous (n=12; 10 male) or allogeneic (n=28; 11 male) HSCT for up to 12 months post HSCT and determined adiponectin and resistin serum concentrations using enzyme-linked immunosorbent assay. RESULTS: There were no significant differences in adiponectin levels (18.5 vs 9.3 MUg/mL, P=0.071) and adiponectin/BMI ratio (0.82 vs 0.39, P=0.068) between patients with acute GVHD grades 2-4 and autologous controls. However, resistin values were significantly lower in patients with acute GVHD grades 2-4 than in autologous controls (4.6 vs 7.3 ng/mL, P=0.030). Adiponectin levels were higher in patients with chronic GVHD (n=17) than in autologous controls (13.5 vs 7.6 MUg/mL, P=0.051), but the difference was not significant. Adiponectin/BMI ratio was significantly higher in patients with chronic GVHD than in autologous controls (0.59 vs 0.25, P=0.006). Patients dying from relapse also had significantly lower adiponectin levels (8.2 MUg/mL) and adiponectin/BMI ratio (0.3) on admission than surviving allogeneic (15.8 ug/mL, P=0.030 and 0.7, P=0.004) and surviving autologous patients (19.2 MUg/mL, P=0.031 and 0.7, P=0.021). CONCLUSION: Adiponectin and resistin levels were altered in patients with acute and chronic GVHD compared to autologous controls and were associated with overall survival and relapse mortality in patients undergoing allogeneic HSCT. PMID- 27374828 TI - Joint and fascial chronic graft-vs-host disease: correlations with clinical and laboratory parameters. AB - AIM: To determine if there are correlations between joint and fascial chronic graft-vs-host disease (cGVHD) with clinical findings, laboratory parameters, and measures of functional capacity. METHODS: 29 patients were diagnosed with cGVHD based on National Institutes of Health (NIH) Consensus Criteria at the University Hospital Centre Zagreb from October 2013 to October 2015. Physical examination, including functional measures such as 2-minute walk test and hand grip strength, as well as laboratory tests were performed. The relationship between these evaluations and the severity of joint and fascial cGVHD was tested by logistical regression analysis. RESULTS: 12 of 29 patients (41.3%) had joint and fascial cGVHD diagnosed according to NIH Consensus Criteria. There was a significant positive correlation of joint and fascial cGVHD and skin cGVHD (P<0.001), serum C3 complement level (P=0.045), and leukocytes (P=0.032). There was a significant negative correlation between 2-minute walk test (P=0.016), percentage of cytotoxic T cells CD3+/CD8+ (P=0.022), serum albumin (P=0.047), and Karnofsky score (P<0.001). Binary logistic regression model found that a significant predictor for joint and fascial cGVHD was cGVHD skin involvement (odds ratio, 7.79; 95 confidence interval 1.87-32.56; P=0.005). CONCLUSION: Joint and fascial cGVHD manifestations correlated with multiple laboratory measurements, clinical features, and cGVHD skin involvement, which was a significant predictor for joint and fascial cGVHD. PMID- 27374829 TI - Vitamin D levels and their associations with survival and major disease outcomes in a large cohort of patients with chronic graft-vs-host disease. AB - AIM: To identify the factors associated with vitamin D status in patients with chronic graft-vs-host disease (cGVHD) and evaluate the association between serum vitamin D (25(OH)D) levels and cGVHD characteristics and clinical outcomes defined by the National Institutes of Health (NIH) criteria. METHODS: 310 cGVHD patients enrolled in the NIH cGVHD natural history study (clinicaltrials.gov: NCT00092235) were analyzed. Univariate analysis and multiple logistic regression were used to determine the associations between various parameters and 25(OH)D levels, dichotomized into categorical variables: <=20 and >20 ng/mL, and as a continuous parameter. Multiple logistic regression was used to develop a predictive model for low vitamin D. Survival analysis and association between cGVHD outcomes and 25(OH)D as a continuous as well as categorical variable: <=20 and >20 ng/mL; <50 and >=50 ng/mL, and among three ordered categories: <=20, 20 50, and >=50 ng/mL, was performed. RESULTS: 69 patients (22.3%) had serum 25(OH)D <=20 ng/mL. Univariate analysis showed that supplement intake, nutritional status (severely malnourished, moderately malnourished, well-nourished), race (African American, other), and estimated creatinine clearance (eCCr) were associated with 25(OH)D levels. A predictive model was developed based on supplement intake, nutritional status, race, and eCCr, accurately predicting 77.9% of patients with 25(OH)D <=20 and 65.2% of those with 25(OH)D >20 ng/mL. No association was found between vitamin D and major cGVHD characteristics, but patients with 25(OH)D <=20 ng/mL had somewhat decreased survival. CONCLUSION: Nutritional status and adequate supplementation are important to maintain 25(OH)D >20 ng/mL in cGVHD patients. Intervention studies and more research is needed to reveal the underlying mechanism of vitamin D metabolism in cGVHD setting. PMID- 27374831 TI - The effects of lumboperitoneal and ventriculoperitoneal shunts on the cranial and spinal cerebrospinal fluid volume in a patient with idiopathic intracranial hypertension. AB - Lumboperitoneal (LP) and ventriculoperitoneal (VP) shunts are a frequent treatment modality for idiopathic intracranial hypertension (IIH). Although these shunts have been used for a long time, it is still not clear how they change the total craniospinal CSF volume and what portions of cranial and spinal CSF are affected. This report for the first time presents the results of a volumetric analysis of the total cranial and spinal CSF space in a patient with IIH. We performed an automated segmentation of the cranial and a manual segmentation of the spinal CSF space first with an LP shunt installed and again after the LP shunt was replaced by a VP shunt. When the LP shunt was in place, the total CSF volume was smaller than when the VP shunt was in place (222.4 cm(3) vs 279.2 cm(3)). The difference was almost completely the result of the spinal CSF volume reduction (49.3 cm(3) and 104.9 cm(3) for LP and VP, respectively), while the cranial CSF volume was not considerably altered (173.2 cm(3) and 174.2 cm(3) for LP and VP, respectively). This report indicates that LP and VP shunts in IIH do not considerably change the cranial CSF volume, while the reduction of CSF volume after LP shunt placement affects almost exclusively the spinal part of the CSF system. Our results suggest that an analysis of both the cranial and the spinal part of the CSF space is necessary for therapeutic procedures planning and for an early recognition of numerous side effects that often arise after shunts placement in IIH patients. PMID- 27374830 TI - Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio help identify patients with lung cancer, but do not differentiate between lung cancer subtypes. AB - AIM: To assess the diagnostic value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in lung cancer (LC). We compared the ratios between healthy participants and all LC patients, as well patients with different pathohistological LC subtypes. METHODS: We retrieved the data on neutrophil, lymphocyte, and platelet levels in 449 patients with different pathohistological LC subtypes (non-small cell LC, small-cell LC, atypical or metastatic LC, neuroendocrine, and sarcomatoid carcinoma) and 47 healthy controls. NLR and PLR were calculated by dividing the absolute number of neutrophils or platelets with the absolute number of lymphocytes. RESULTS: There were significant differences in both NLR and PLR (P<0.001) between all LC patients and the control group, but there were no differences between patients with different LC subtypes. Reciever operating characteristics analysis for NLR showed the optimal cut-off value of 2.71, with a sensitivity of 77.05% and specificity of 87.23%. The optimal cut-off value for PLR was 182.31, with a sensitivity of 51.09% and specificity of 91.49%. CONCLUSION: The results showed that the NLR and PLR may have added value in the early diagnosis of LC, but further research is needed to confirm these results. PMID- 27374832 TI - The filter bubble and its effect on online personal health information. PMID- 27374833 TI - Derivation and Validation of a Severity Scoring Method for the 3-Minute Diagnostic Interview for Confusion Assessment Method--Defined Delirium. AB - OBJECTIVES: To derive and validate a method for scoring delirium severity using a recently validated, brief, structured diagnostic interview for Confusion Assessment Method (CAM)-defined delirium (3D-CAM) and to demonstrate its agreement with the CAM Severity short form (CAM-S SF) as the reference standard. DESIGN: Derivation and validation analysis in a prospective cohort study. SETTING: Two academic medical centers. PARTICIPANTS: Individuals aged 70 and older enrolled in the Successful Aging after Elective Surgery Study undergoing major elective noncardiac surgery (N = 566). MEASUREMENTS: The sample was randomly divided into a derivation dataset (n = 377) and an independent validation dataset (n = 189). These datasets were used to develop a severity scoring method using the 3D-CAM based on the four-item CAM-S SF (3D-CAM-S) and evaluate agreement between the 3D-CAM-S and the traditional CAM-S SF using weighted kappa statistics. RESULTS: A method for scoring severity using 3D-CAM items was developed that achieved good agreement with the CAM-S SF in the derivation dataset (kappa = 0.94, 95% confidence interval (CI) = 0.93-0.95). The 3D-CAM-S achieved nearly identical agreement in the independent validation dataset (kappa = 0.93, 95% CI = 0.92-0.95), and 100% of 3D-CAM-S scores were within 1 point of the CAM-S SF score in both datasets. The 3D-CAM-S also strongly predicts clinical outcomes. CONCLUSION: A newly developed method for scoring delirium severity using the 3D-CAM (the 3D-CAM-S) has excellent agreement with the CAM-S SF. This new methodology enables clinicians and researchers using the 3D-CAM for surveillance to measure delirium severity and monitor its course simultaneously by tracking changes over time. The 3D-CAM-S expands the utility of the 3D-CAM as an important tool for delirium recognition and management. PMID- 27374834 TI - Comparison of the serum toxicokinetics of larkspur toxins in cattle, sheep and goats. AB - Larkspurs (Delphinium spp.) are a major cause of cattle losses in western North America, whereas sheep are thought to be resistant to larkspur toxicosis. Goats are often used as a small ruminant model to study poisonous plants. In this study, we compared the serum toxicokinetic profile of toxic larkspur alkaloids from Delphinium barbeyi in cattle, goats, and sheep. The results from this study indicate that kinetic differences could partially explain species differences in susceptibility to larkspur toxicosis. PMID- 27374835 TI - Ten-year analyses of the German DRG data about negative pressure wound therapy. AB - Exact data regarding the clinical role of negative pressure wound therapy (NPWT) for wound care in a specific country are not available. Thus, we analysed the use of NPWT in hospitalised patients in Germany. Detailed lists of all hospitalised cases treated with NPWT in Germany for each of the years from 2005 to 2014 were obtained from the Federal Statistical Office, as well as lists of the 15 most frequent principal and additional diagnoses documented with NPWT in 2014. Within the 10-year time period of the study, the number of cases treated with NPWT increased by 349%, from 37 053 in 2005 to 129 269 in 2014. The rate of all hospitalised cases treated with NPWT increased form 0.22% to 0.66% in Germany. In 2014, wounds affecting skin and subcutaneous tissue (5-916.a0) are the most frequent documented indication for NPWT followed by deep wounds involving bones and joints at the limbs (5-916.a1). Open abdomens (5-916.a3) count for higher numbers than deep wounds of the thorax, mediastinum and sternum (5-916.a2). Fifty percent of all cases hospitalised for stage IV pressure ulcers at sacrum or ischium and around one third (32.2%) of cases with pyothorax received NPWT. Every fourth to fifth case hospitalised for disruption of surgical wounds or infections following a procedure (24.1%), as well as for infections and inflammations because of internal joint prosthesis or because of an internal fixation device was treated with NPWT (22.9%). In cases with diabetic foot syndrome, it is still every tenth case (10.1%). This analysis shows a substantial increase in the use of NPWT in the last decade for hospitalised patients. NPWT has a fixed role in the treatment of stage IV pressure ulcers at sacrum or ischium, pyothorax, infection and inflammation because of internal joint prosthesis or an internal fixation device and diabetic foot syndrome. PMID- 27374836 TI - Betaine and Carnitine Derivatives as Herbicidal Ionic Liquids. AB - This study focused on the synthesis and subsequent characterization of herbicidal ionic liquids based on betaine and carnitine, two derivatives of amino acids, which were used as cations. Four commonly used herbicides (2,4-D, MCPA, MCPP and Dicamba) were used as anions in simple (single anion) and oligomeric (two anions) salts. The obtained salts were subjected to analyzes regarding physicochemical properties (density, viscosity, refractive index, thermal decomposition profiles and solubility) as well as evaluation of their herbicidal activity under greenhouse and field conditions, toxicity towards rats and biodegradability. The obtained results suggest that the synthesized herbicidal ionic liquids displayed low toxicity (classified as category 4 compounds) and showed similar or improved efficacy against weed compared to reference herbicides. The highest increase was observed during field trials for salts containing 2,4-D as the anion, which also exhibited the highest biodegradability (>75 %). PMID- 27374837 TI - Integrated data mining of transcriptomic and proteomic datasets to predict the secretome of adipose tissue and muscle in ruminants. AB - Adipose tissue and muscle are endocrine organs releasing signalling and mediator proteins termed adipokines and myokines, enabling functioning of the organism and its adaption to a wide range of different challenges such as starvation, overfeeding, stress and diseases. They also contribute to the "adipose-muscular" cross-talk for an integrated control of body mass composition. This article integrates transcriptomic and proteomic data available in ruminant species (mainly in bovine, and when available in ovine and caprine) to computationally predict the large-scale secretome of adipose tissues and muscles. For this purpose predictive bioinformatics algorithms were employed to identify proteins putatively secreted by tissues thanks to a signal peptide. We predicted 1749 secreted proteins that were found from adipose tissues and muscles, more than a half of them being already declared as secreted proteins in public repositories. We also identified 188 and 357 proteins in the predictive secretome of adipose tissues and muscles respectively, only a minor part (3-11%) of them being reported in the overlap of public repositories used for comparison. Functional analysis of these proteins highlights their involvement in biological pathways known to sustain tissue growth and functioning. This strategy allowed us to identify some known and putative novel adipomyokines, adipokines and myokines. However their role and their expression signature depending on rearing practices remain largely to be explored. PMID- 27374839 TI - Relevance of Changes in Serum Creatinine During a Heart Failure Trial of Decongestive Strategies: Insights From the DOSE Trial. AB - BACKGROUND: Worsening renal function (WRF) is a common endpoint in decompensated heart failure clinical trials because of associations between WRF and adverse outcomes. However, WRF has not universally been identified as a poor prognostic sign, challenging the validity of WRF as a surrogate endpoint. Our aim was to describe the associations between changes in creatinine and adverse outcomes in a clinical trial of decongestive therapies. METHODS AND RESULTS: We investigated the association between changes in creatinine and the composite endpoint of death, rehospitalization or emergency room visit within 60 days in 301 patients in the Diuretic Optimization Strategies Evaluation (DOSE) trial. WRF was defined as an increase in creatinine >0.3 mg/dL and improvement in renal function (IRF) as a decrease >0.3 mg/dL. When examining linear changes in creatinine from baseline to 72 hours (the coprimary endpoint of DOSE), increasing creatinine was associated with lower risk for the composite outcome (HR = 0.81 per 0.3 mg/dL increase, 95% CI 0.67-0.98, P = .026). Compared with patients with stable renal function (n = 219), WRF (n = 54) was not associated with the composite endpoint (HR = 1.17, 95% CI = 0.77-1.78, P = .47). However, compared with stable renal function, there was a strong relationship between IRF (n = 28) and the composite endpoint (HR = 2.52, 95% CI = 1.57-4.03, P < .001). CONCLUSION: The coprimary endpoint of the DOSE trial, a linear increase in creatinine, was paradoxically associated with improved outcomes. This was driven by absence of risk attributable to WRF and a strong risk associated with IRF. These results argue against using changes in serum creatinine as a surrogate endpoint in trials of decongestive strategies. PMID- 27374840 TI - Left Ventricular Assist Devices or Inotropes for Decreasing Pulmonary Vascular Resistance in Patients with Pulmonary Hypertension Listed for Heart Transplantation. AB - BACKGROUND: Fixed pulmonary hypertension is common in patients with advanced heart failure and is a contraindication for heart transplantation. Left ventricular assist devices (LVAD) and inotropes have been used to reduce pulmonary vascular resistance (PVR) and allow transplantation. However, little is known about the efficacy of this strategy. METHODS: We queried the United Network for Organ Sharing registry for all adult patients (age >=18 years) listed for primary heart transplantation (2008-2014) with PVR of >5 wood units (WU) or transpulmonary gradient >16 mmHg who were treated with LVAD or IV inotropes as status 1a, 1b, or 7. We compared waitlist mortality/delisting and absolute changes in hemodynamics between listing and transplantation. RESULTS: Of 18,009 patients listed during the study period, 1016 were included in the analysis (393 LVAD, 623 inotropes), with a mean age of 52.9 +/- 11.6 years, 74% male, and 38% had ischemic etiology. Mean PVR was 5.7 +/- 2.4 WU and transpulmonary pressure gradient 19.3 +/- 5.3 mmHg. Compared with the inotrope group, LVAD patients were more likely listed as status 1A (32.8% vs 18.1%, P < .001), had lower PVR (5.3 WU vs 5.9 WU, P = .001), and higher cardiac output (4.1 vs 3.6 L/min, P < .001). After a mean of 239 days, PVR decreased by 1.71 WU in the LVAD group vs 1.85 WU in the inotrope group (P = .52). PVR normalization (<2.5 WU) occurred at similar rates among those treated with inotropes and LVAD (30.7% vs 35.6%, P = .228). Waitlist mortality was similar between LVAD and inotropes (adjusted P = .837). Absolute PVR and transpulmonary pressure gradient reductions correlated with time on the waitlist (P < .001 for both comparisons). CONCLUSION: Only about one-third of patients with fixed pulmonary hypertension achieve normalization of PVR before transplant with either LVAD or inotropes. Similar waitlist mortality was observed among patients bridged with either strategy. PMID- 27374838 TI - What Are Effective Program Characteristics of Self-Management Interventions in Patients With Heart Failure? An Individual Patient Data Meta-analysis. AB - BACKGROUND: To identify those characteristics of self-management interventions in patients with heart failure (HF) that are effective in influencing health-related quality of life, mortality, and hospitalizations. METHODS AND RESULTS: Randomized trials on self-management interventions conducted between January 1985 and June 2013 were identified and individual patient data were requested for meta analysis. Generalized mixed effects models and Cox proportional hazard models including frailty terms were used to assess the relation between characteristics of interventions and health-related outcomes. Twenty randomized trials (5624 patients) were included. Longer intervention duration reduced mortality risk (hazard ratio 0.99, 95% confidence interval [CI] 0.97-0.999 per month increase in duration), risk of HF-related hospitalization (hazard ratio 0.98, 95% CI 0.96 0.99), and HF-related hospitalization at 6 months (risk ratio 0.96, 95% CI 0.92 0.995). Although results were not consistent across outcomes, interventions comprising standardized training of interventionists, peer contact, log keeping, or goal-setting skills appeared less effective than interventions without these characteristics. CONCLUSION: No specific program characteristics were consistently associated with better effects of self-management interventions, but longer duration seemed to improve the effect of self-management interventions on several outcomes. Future research using factorial trial designs and process evaluations is needed to understand the working mechanism of specific program characteristics of self-management interventions in HF patients. PMID- 27374841 TI - Gastrointestinal risk assessment in patients requiring non-steroidal anti inflammatory drugs for osteoarthritis: The GIRANO study. AB - OBJECTIVE: To evaluate gastrointestinal risk profiles in patients with osteoarthritis who are currently being treated, or who are candidates for treatment, with a non-steroidal anti-inflammatory drug. METHODS: Patients with osteoarthritis treated by primary care physicians or physical and rehabilitation medicine (PRM) specialists in Belgium and Luxembourg were scored for gastrointestinal risk profile, low, moderate or high, based on the presence of gastrointestinal risk factors. These included advanced age, gastrointestinal history, comorbidities, medication use, smoking, and alcohol consumption. Use of gastro-protective agents (proton pump inhibitors) was also assessed. RESULTS: A total of 190 primary care physicians and PRM specialists provided data on 885 patients. A large majority of patients were rated high-risk gastrointestinal (77.8%), with fewer moderate (19.4%) or low (2.8%) risk. The proportion of high risk patients treated by PRM specialists was significantly lower than that treated by primary care physicians (64.7% vs 79.9%; p < 0.0001). Only 37.0% of high-risk patients received proton pump inhibitors co-prescription with a non steroidal anti-inflammatory drug. CONCLUSION: A high prevalence of elevated gastrointestinal risk was found in this survey of patients with osteoarthritis who were current or candidate users of non-steroidal anti-inflammatory drugs. This appears to be insufficiently recognized, as preventative gastro-protective co-treatment was infrequently prescribed. Careful assessment of gastrointestinal risk factors should be made before prescribing non-steroidal anti-inflammatory drugs, with treatment tailored to the patient's gastrointestinal risk profile. PMID- 27374842 TI - Basic research on appetite regulation: Social context of a meal is missing. PMID- 27374843 TI - Efficiency of chlorophyll in gross primary productivity: A proof of concept and application in crops. AB - One of the main factors affecting vegetation productivity is absorbed light, which is largely governed by chlorophyll. In this paper, we introduce the concept of chlorophyll efficiency, representing the amount of gross primary production per unit of canopy chlorophyll content (Chl) and incident PAR. We analyzed chlorophyll efficiency in two contrasting crops (soybean and maize). Given that they have different photosynthetic pathways (C3 vs. C4), leaf structures (dicot vs. monocot) and canopy architectures (a heliotrophic leaf angle distribution vs. a spherical leaf angle distribution), they cover a large spectrum of biophysical conditions. Our results show that chlorophyll efficiency in primary productivity is highly variable and responds to various physiological and phenological conditions, and water availability. Since Chl is accessible through non destructive, remotely sensed techniques, the use of chlorophyll efficiency for modeling and monitoring plant optimization patterns is practical at different scales (e.g., leaf, canopy) and under widely-varying environmental conditions. Through this analysis, we directly related a functional characteristic, gross primary production with a structural characteristic, canopy chlorophyll content. Understanding the efficiency of the structural characteristic is of great interest as it allows explaining functional components of the plant system. PMID- 27374845 TI - Effects and mechanism of action of isatin, a MAO inhibitor, on in vivo striatal dopamine release. AB - Isatin is an endogenous indole that inhibits monoamine oxidase (MAO), being more selective for MAO-B than MAO-A isoform. By inhibiting MAO, isatin increases dopamine levels in the brain and, in animal models of Parkinson's disease (PD) isatin is able to prevent dopamine depletion. Contradictorily, some studies indicate that isatin did not increase striatal dopamine levels, although it was able to improve the motor signs in PD model. Given these conflicting data, our aim was to study the effects and neurochemical mechanisms of action of isatin on in vivo dopamine release from rat dorsal striatum using brain microdialysis technique in conscious and freely moving animals. Our results showed that intrastriatal administration of 1, 5 or 10 mM isatin, for 1 h, significantly increased dopamine levels to 355 +/- 104%, 700 +/- 72%, and 1241 +/- 146%, when compared with basal values, respectively. The highest concentration of isatin (10 mM) was used to investigate whether the dopamine overflow is due to an exocytotic release or due to a possible action on dopamine transporter (DAT). The removal of Ca(++) from medium, administration of TTX (10 MUM), or pretreatment with reserpine (10 mg/kg) significantly decreased by 90%, 83%, and 78%, respectively, the effect of isatin on dopamine levels. The blockade of DAT with nomifensine (50 MUM) did not alter the effect of isatin; and isatin significantly increased the depolarization-evoked release of dopamine. These results suggest that isatin induced dopamine release depends on vesicular dopamine content, and takes place due to a previous entry of Ca(++) and terminal depolarization. PMID- 27374844 TI - The two-step development of a duplex retina involves distinct events of cone and rod neurogenesis and differentiation. AB - Unlike in mammals, persistent postembryonic retinal growth is a characteristic feature of fish, which includes major remodeling events that affect all cell types including photoreceptors. Consequently, visual capabilities change during development, where retinal sensitivity to different wavelengths of light (photopic vision), -and to limited photons (scotopic vision) are central capabilities for survival. Differently from well-established model fish, Atlantic cod has a prolonged larval stage where only cone photoreceptors are present. Rods do not appear until juvenile transition (metamorphosis), a hallmark of indirect developing species. Previously we showed that whole gene families of lws (red sensitive) and sws1 (UV-sensitive) opsins have been lost in cod, while rh2a (green-sensitive) and sws2 (blue-sensitive) genes have tandem duplicated. Here, we provide a comprehensive characterization of a two-step developing duplex retina in Atlantic cod. The study focuses on cone subtype dynamics and delayed rod neurogenesis and differentiation in all cod life stages. Using transcriptomic and histological approaches we show that different opsins disappear in a topographic manner during development where central to peripheral retina is a key axis of expressional change. Early cone differentiation was initiated in dorso temporal retina different from previously described in fish. Rods first appeared during initiation of metamorphosis and expression of the nuclear receptor transcription factor nr2e3-1, suggest involvement in rod specification. The indirect developmental strategy thus allows for separate studies of cones and rods development, which in nature correlates with visual changes linked to habitat shifts. The clustering of key retinal genes according to life stage, suggests that Atlantic cod with its sequenced genome may be an important resource for identification of underlying factors required for development and function of photopic and scotopic vision. PMID- 27374846 TI - The Fielding H. Garrison Lecture: "Break-Bone" Fever in Philadelphia, 1780: Reflections on the History of Disease. AB - In the Autumn of 1780 an epidemic hit the city of Philadelphia. The symptoms of the disease resembled those of present day dengue fever, and subsequent observers argued that the disease was in fact dengue. But was it? The question forces us to confront the challenges of retrospective epidemiology and how we examine the history of a disease. This paper examines the 1780 epidemic from two perspectives. First, it looks at evidence that the disease was dengue and examines what this tells us about the epidemic and the conditions that caused it. Second, it looks at the disease from the perspective of Dr. Benjamin Rush, who treated hundreds of patients during the epidemic. In other words, it examines the disease through the lens of eighteenth century medical ideas. The paper concludes that each approach is valuable and reveals different aspects of the relationship between society and disease. PMID- 27374847 TI - Spines of Steel: A Case of Surgical Enthusiasm in Cold War America. AB - Just as the prevalence of scoliosis began to decline precipitously after World War II, American orthopedic surgeon Dr. Paul R. Harrington devised a new, invasive surgical system whereby implantable prosthetic metal rods and hooks were used to straighten curved backs. By the 1970s, "Harrington rods" had become the gold standard of surgical scoliosis care in the United States, replacing more conventional methods of exercise, bracing, and casting. This article situates the success of Harrington rods within a much larger and historically longer debate about why, when compared to those in other nations, American surgeons appear to be "more aggressive" and "knife-happy." Using Harrington's papers and correspondence, I argue that patients played a vital role in the rise of spinal surgery. As such, this article examines not only how surgical enthusiasm has been historically measured, defined, and morally evaluated, but also how scoliosis became classified as a debility in need of surgical management. PMID- 27374848 TI - Photographing AIDS: On Capturing a Disease in Pictures of People with AIDS. AB - The photography of people with AIDS has been subject to numerous critiques in the 1980s and has become a controversial way of visualizing the AIDS epidemic. While most of the scholarly work on AIDS photography is based in cultural studies and concerned with popular representations, the clinical value of photographs of people with AIDS usually remains overlooked. This article addresses photographs as a "way of seeing" AIDS that contributed crucially to the making of the disease entity AIDS within the history of medicine. Cultural studies methods are applied to analyze clinical photography in the case of AIDS, thus contributing to the medical history of AIDS through the lens of photography. The article reveals the conflation of disease morphology and patient identity as a characteristic feature of both clinical photography and a now historical nature of AIDS. PMID- 27374849 TI - Plague Doctors in the HIV/AIDS Epidemic: Mental Health Professionals and the "San Francisco Model," 1981-1990. AB - Psychiatrists, psychologists, and other mental health professionals were among the first and most crucial responders to HIV/AIDS. Given an epidemic in which behavior and identity played fundamental roles, mental health professionals were uniquely positioned to conduct social research to explain the existence and spread of disease; to develop clinical understanding of psychological aspects of HIV/AIDS as they emerged; and to collaborate with affected communities to promote education and behavioral change. This study examines the roles of mental health professionals as "plague doctors" in San Francisco's response to HIV/AIDS, in the early years of the epidemic. Among the many collaborations and projects that distinguished the "San Francisco model" of response to this plague, bathhouse based epidemiology, consult-liaison psychiatry, and community partnerships for counseling and education are examined in detail as illustrations of the epidemic changing engagement of the mental health community. PMID- 27374850 TI - News and Events. PMID- 27374852 TI - Inhibition of mitochondrial fusion is an early and critical event in breast cancer cell apoptosis by dietary chemopreventative benzyl isothiocyanate. AB - Benzyl isothiocyanate (BITC) is a highly promising phytochemical abundant in cruciferous vegetables with preclinical evidence of in vivo efficacy against breast cancer in xenograft and transgenic mouse models. Mammary cancer chemoprevention by BITC is associated with apoptotic cell death but the underlying mechanism is not fully understood. Herein, we demonstrate for the first time that altered mitochondrial dynamics is an early and critical event in BITC-induced apoptosis in breast cancer cells. Exposure of MCF-7 and MDA-MB-231 cells to plasma achievable doses of BITC resulted in rapid collapse of mitochondrial filamentous network. BITC treatment also inhibited polyethyleneglycol-induced mitochondrial fusion. In contrast, a normal human mammary epithelial cell line (MCF-10A) that was derived from fibrocystic breast disease, was resistant to BITC-mediated alterations in mitochondrial dynamics as well as apoptosis. Transient or sustained decrease in levels of proteins engaged in regulation of mitochondrial fission and fusion was clearly evident after BITC treatment in both cancer cell lines. A trend for a decrease in the levels of mitochondrial fission- and fusion-related proteins was also observed in vivo in tumors of BITC-treated mice compared with control. Immortalized mouse embryonic fibroblasts from Drp1 knockout mice were resistant to BITC-induced apoptosis when compared with those from wild-type mice. Upon treatment with BITC, Bak dissociated from mitofusin 2 in both MCF-7 and MDA-MB-231 cells suggesting a crucial role for interaction of Bak and mitofusins in BITC-mediated inhibition of fusion and morphological dynamics. In conclusion, the present study provides novel insights into the molecular complexity of BITC-induced cell death. PMID- 27374854 TI - Primordial germ cell-like cells derived from canine adipose mesenchymal stem cells. AB - OBJECTIVES: Previous studies have shown that adipose mesenchymal stem cells (AMSCs) share the potency of typical bone marrow mesenchymal stem cells (MSCs); however, there is little information concerning characteristics of canine AMSCs (CAMSCs); it has not previously been made clear whether CAMSCs would be able to differentiate into other cell types. MATERIALS AND METHODS: In this study, typical AMSC lines were established, and their characteristics including morphology, typical markers and differentiation potentiality were tested. RESULTS: The cells exhibited typical MSC morphology and were positive for CD90, CD44 and CD166, considered to be MSCs surface markers. They were negative for CD34 and CD45. The CAMSCs also exhibited embryonic stem cell (ESC) markers, including Oct4 and Sox2, at passage 2. In an appropriate microenvironment, CAMSCs differentiated into EBs and were able to produce cells of the three germ layers. These results indicate that established cells were putative adipocyte-derived MSCs, which also displayed properties of ESCs. Moreover, when the CAMSCs were induced by bone morphogenetic protein 4 (BMP4), they differentiated into PGC-like cells (PGCLCs) and male germ-like cells, which were positive for PR domain containing 1 (Prdm1), PR domain-containing 14 (Prdm14), doublesex and mab-3 related transcription factor (Dmrt1), as well as for promyelocytic leukaemia zinc finger (Plzf). Quantitative real-time PCR (qRT-PCR) and western blotting analysis verified higher expression levels of these markers. CONCLUSION: This study provides an efficient approach to study germ cell development using CAMSCs. PMID- 27374855 TI - Malleable and Recyclable Poly(urea-urethane) Thermosets bearing Hindered Urea Bonds. AB - Poly(urea-urethane) thermosets containing the 1-tert-butylethylurea (TBEU) structure feature a reversible dissociation/association process of their covalent linkages under mild conditions. Unlike conventional thermosets, TBEU-based poly(urea-urethane) thermosets maintain their malleability after curing. Under high temperature (100 degrees C) and applied pressure (300 kPa), ground TBEU thermoset powder can be remolded to bulk after 20 min. PMID- 27374853 TI - Secondary coenzyme Q10 deficiencies in oxidative phosphorylation (OXPHOS) and non OXPHOS disorders. AB - We evaluated the coenzyme Q10 (CoQ) levels in patients who were diagnosed with mitochondrial oxidative phosphorylation (OXPHOS) and non-OXPHOS disorders (n=72). Data from the 72 cases in this study revealed that 44.4% of patients showed low CoQ concentrations in either their skeletal muscle or skin fibroblasts. Our findings suggest that secondary CoQ deficiency is a common finding in OXPHOS and non-OXPHOS disorders. We hypothesize that cases of CoQ deficiency associated with OXPHOS defects could be an adaptive mechanism to maintain a balanced OXPHOS, although the mechanisms explaining these deficiencies and the pathophysiological role of secondary CoQ deficiency deserves further investigation. PMID- 27374858 TI - Introduction to U13 supplement. PMID- 27374857 TI - An Artificial Reaction Promoter Modulates Mitochondrial Functions via Chemically Promoting Protein Acetylation. AB - Acetylation, which modulates protein function, is an important process in intracellular signalling. In mitochondria, protein acetylation regulates a number of enzymatic activities and, therefore, modulates mitochondrial functions. Our previous report showed that tributylphosphine (PBu3), an artificial reaction promoter that promotes acetylransfer reactions in vitro, also promotes the reaction between acetyl-CoA and an exogenously introduced fluorescent probe in mitochondria. In this study, we demonstrate that PBu3 induces the acetylation of mitochondrial proteins and a decrease in acetyl-CoA concentration in PBu3-treated HeLa cells. This indicates that PBu3 can promote the acetyltransfer reaction between acetyl-CoA and mitochondrial proteins in living cells. PBu3-induced acetylation gradually reduced mitochondrial ATP concentrations in HeLa cells without changing the cytoplasmic ATP concentration, suggesting that PBu3 mainly affects mitochondrial functions. In addition, pyruvate, which is converted into acetyl-CoA in mitochondria and transiently increases ATP concentrations in the absence of PBu3, elicited a further decrease in mitochondrial ATP concentrations in the presence of PBu3. Moreover, the application and removal of PBu3 reversibly alternated mitochondrial fragmentation and elongation. These results indicate that PBu3 enhances acetyltransfer reactions in mitochondria and modulates mitochondrial functions in living cells. PMID- 27374856 TI - The Uyghur population and genetic susceptibility to type 2 diabetes: potential role for variants in CAPN10, APM1 and FUT6 genes. AB - Genome-wide association studies have successfully identified over 70 loci associated with the risk of type 2 diabetes mellitus (T2DM) in multiple populations of European ancestry. However, the risk attributable to an individual variant is modest and does not yet provide convincing evidence for clinical utility. Association between these established genetic variants and T2DM in general populations is hitherto understudied in the isolated populations, such as the Uyghurs, resident in Hetian, far southern Xinjiang Uyghur Autonomous Region, China. In this case-control study, we genotyped 13 single-nucleotide polymorphisms (SNPs) at 10 genes associated with diabetes in 130 cases with T2DM and 135 healthy controls of Uyghur, a Chinese minority ethnic group. Three of the 13 SNPs demonstrated significant association with T2DM in the Uyghur population. There were significant differences between the T2DM patients and controls in the risk allele distributions of rs3792267 (CAPN10) (P = 0.002), rs1501299 (APM1) (P = 0.017), and rs3760776 (FUT6) (P = 0.031). Allelic carriers of rs3792267-A, rs1501299-T, and rs3760776-T had a 2.24-fold [OR (95% CI): 1.35-3.71], 0.59-fold [OR (95% CI): 0.39-0.91], 0.57-fold [OR (95% CI): 0.34-0.95] increased risk for T2DM respectively. We further confirmed that the cumulative risk allelic scores calculated from the 13 susceptibility loci for T2DM differed significantly between the T2DM patients and controls (P = 0.001), and the effect of obesity/overweight on T2DM was only observed in the subjects with a combined risk allelic score under a value of 17. This study observed that the SNPs rs3792267 in CAPN10, rs1501299 in APM1, and rs3760776 in FUT6 might serve as potential susceptible biomarkers for T2DM in Uyghurs. The cumulative risk allelic scores of multiple loci with modest individual effects are also significant risk factors in Uyghurs for T2DM, particularly among non-obese individuals. This is the first investigation having observed/found genetic variations on genetic loci functionally linked with glycosylation associated with the risk of T2DM in a Uyghur population. PMID- 27374860 TI - Extensive myelitis revealing common variable immunodeficiency. PMID- 27374859 TI - The electrophysiology of thyroid surgery: electrophysiologic and muscular responses with stimulation of the vagus nerve, recurrent laryngeal nerve, and external branch of the superior laryngeal nerve. AB - OBJECTIVES/HYPOTHESIS: Correlation of physiologically important electromyographic (EMG) waveforms with demonstrable muscle activation is important for the reliable interpretation of evoked waveforms during intraoperative neural monitoring (IONM) of the vagus nerve, recurrent laryngeal nerve (RLN), and external branch of the superior laryngeal nerve (EBSLN) in thyroid surgery. STUDY DESIGN: Retrospective chart review. METHODS: Data were reviewed retrospectively for thyroid surgery patients with laryngeal nerve IONM from January to December, 2015. EMG responses to monopolar stimulation of the vagus/RLN and EBSLN were recorded in bilateral vocalis, cricothyroid (CTM), and strap muscles using endotracheal tube-based surface and intramuscular hook electrodes, respectively. Target muscles for vagal/RLN and EBSLN stimulation were the ipsilateral vocalis and CTM, respectively. All other recording channels were nontarget muscles. RESULTS: Fifty surgical sides were identified in 37 subjects. All target muscle mean amplitudes were significantly higher than in nontarget muscles. With vagal/RLN stimulation, target ipsilateral vocalis mean amplitude was 1,095.7 MUV (mean difference range = -814.1 to -1,078 MUV, P < .0001). For EBSLN stimulation, target ipsilateral CTM mean amplitude was 6,379.3 MUV (mean difference range = -6,222.6 to -6,362.3 MUV, P < .0001). Target muscle large-amplitude EMG responses correlated with meaningful visual or palpable muscular responses, whereas nontarget EMG responses showed no meaningful muscle activation. CONCLUSIONS: Target and nontarget laryngeal muscles are differentiated based on divergence of EMG response directly correlating with presence or absence of visual and palpable muscle activation. Low-amplitude EMG waveforms in nontarget muscles with neural stimulation can be explained by the concept of far-field artifactual waveforms and do not correspond to a true muscular response. The surgeon should be aware of these nonphysiologic waveforms when interpreting and applying IONM during thyroid surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:764-771, 2017. PMID- 27374861 TI - Veno-Arterial ECMO in the Setting of Post-Infarct Ventricular Septal Defect: A Bridge to Surgical Repair. AB - Extracorporeal membrane oxygenation (ECMO) is a complex rescue therapy utilised to provide circulatory and/or respiratory support to critically ill patients who have failed maximal conventional therapy. The use of ECMO in adult cardiac surgery is not routine, occurring in a minority of critically ill patients, typically postoperatively. Presented here are three cases of post-infarct ventricular septal defect with cardiogenic shock managed preoperatively with ECMO support as a bridge to definitive surgical closure. We present a review of ECMO in the adult cardiac surgical population and highlight the potential role of preoperative ECMO for cardiogenic shock in the setting of post-infarct ventricular septal defect (PI VSD) as a bridge to definitive closure. PMID- 27374862 TI - Comparison of Safety and Effectiveness Between Right Versus Left Radial Arterial Access in Primary Percutaneous Coronary Intervention for Acute ST Segment Elevation Myocardial Infarction. AB - BACKGROUND: Transradial approach (TRA) is now considered the standard of care in many centres for elective and primary percutaneous intervention (PCI). The use of the radial approach in ST segment elevation myocardial infarction (STEMI) patients has been associated with a significant reduction in major adverse cardiac events. However, it is still unclear if the side of radial access (right vs. left) has impact on safety and effectiveness of TRA in primary PCI. So this study was conducted to compare the safety, feasibility, and outcomes of right radial access (RRA) vs. left radial access (LRA) in the setting of primary PCI. METHODS: We retrospectively analysed the data of 400 consecutive patients presenting to our institution with STEMI for whom primary PCIs were performed via RRA and LRA. RESULTS: Mean age of the whole studied population was 57+/-12.8 years, with male predominance (77.2%). There were 202 cases in the RRA group and 198 in the LRA group, with no significant difference in demographics and clinical characteristics for patients included in both groups. There was no significant difference in procedure success rate (97.5% for RRA vs. 98.4% for LRA; P=0.77). In addition, no significant difference between both approaches was observed in the contrast volume, number of catheters, fluoroscopy time (FT), needle-to balloon time, post-procedure vascular complications, in hospital reinfarction, stroke/transient ischaemic attack (TIA) or death. CONCLUSION: Right radial access and LRA are equally safe and effective in the setting of primary PCI. Both approaches have a high success rate and comparable needle-to-balloon time. PMID- 27374863 TI - A case of infective endocarditis and pyogenic spondylitis after transrectal ultrasound guided prostate biopsy. AB - We report a patient with infective endocarditis and pyrogenic spondylitis occurring simultaneously. The patient was a 59-year-old man. He was suspected of having prostate cancer due to a high prostate-specific antigen concentration noted in a checkup. He then underwent a transrectal ultrasound guided prostate biopsy with cefotiam as antimicrobial prophylaxis. He had a fever higher than 38 degrees C and lumbar pain for a few days after the biopsy. Enterococcus faecalis was isolated from 2 sets of blood culture. Magnetic resonance imaging revealed an abnormal image at C7/Th1 with a signal decrease in T1-weighted sequences and signal increase in T2-weighted sequences that were suspected to be due to bone destruction. Therefore, he was diagnosed as having pyogenic spondylitis by an orthopedist. At the same time, he complained of palpitation and a heart murmur was detected. Then transesophageal echocardiography was performed by a cardiologist and it revealed vegetation in his left ventricle and aortic regurgitation, and finally acute cardiac insufficiency was determined. He was treated with tazobactam/piperacillin and aortic valve displacement surgery. Based on the results of the prostate biopsy and image inspection, he was diagnosed as having localized prostate cancer. He was treated by androgen deprivation therapy and external beam radiation therapy. We have to keep in mind that E. faecalis can be a potential pathogen for severe infectious complications after prostate biopsy, especially if a cephalosporin is selected for antimicrobial prophylaxis. PMID- 27374864 TI - SAFETY AND TOXICITY OF AN ACCELERATED COARSELY FRACTIONATED RADIATION PROTOCOL FOR TREATMENT OF APPENDICULAR OSTEOSARCOMA IN 14 DOGS: 10 GY * 2 FRACTIONS. AB - Coarsely fractionated radiation is commonly used as a method for pain control in dogs with appendicular osteosarcoma, however there is little published information on optimal protocols. The aim of this retrospective, descriptive study was to report safety and toxicity findings in a sample of dogs with appendicular osteosarcoma that had been treated with a radiation scheme of 10 Gy delivered over two consecutive days for a total of 20 Gy. Dogs were included in the study if they had osteosarcoma that was treated with the aforementioned protocol. Dogs were excluded if treated with the same protocol for any other bone tumor besides osteosarcoma or inadequate follow-up. Thirteen of the 14 patients received adjuvant therapy with pamidronate and a nonsteroidal anti-inflammatory. Nine dogs received adjuvant chemotherapy with carboplatin after radiation was complete. Within a median of 14 days, 92.8% of dogs subjectively had improved pain control. Median duration of response (DOR) was 80 days (range 20-365). The majority of patients developed VRTOG grade one toxicity, primarily alopecia. Five dogs (35.7%) developed pathologic fracture postradiation treatment. Timing of fracture was variable ranging from 24 to 250 days. This radiation protocol was well tolerated, with minimal toxicity, subjectively improved survival time, and had the benefit of being completed in two consecutive days. PMID- 27374865 TI - FK506 binding protein 51 integrates pathways of adaptation: FKBP51 shapes the reactivity to environmental change. AB - This review portraits FK506 binding protein (FKBP) 51 as "reactivity protein" and collates recent publications to develop the concept of FKBP51 as contributor to different levels of adaptation. Adaptation is a fundamental process that enables unicellular and multicellular organisms to adjust their molecular circuits and structural conditions in reaction to environmental changes threatening their homeostasis. FKBP51 is known as chaperone and co-chaperone of heat shock protein (HSP) 90, thus involved in processes ensuring correct protein folding in response to proteotoxic stress. In mammals, FKBP51 both shapes the stress response and is calibrated by the stress levels through an ultrashort molecular feedback loop. More recently, it has been linked to several intracellular pathways related to the reactivity to drug exposure and stress. Through its role in autophagy and DNA methylation in particular it influences adaptive pathways, possibly also in a transgenerational fashion. Also see the video abstract here. PMID- 27374866 TI - Rapid recognition and functional analysis of membrane proteins on human cancer cells using atomic force microscopy. AB - Understanding the physicochemical properties of cell surface signalling molecules is important for us to uncover the underlying mechanisms that guide the cellular behaviors. Atomic force microscopy (AFM) has become a powerful tool for detecting the molecular interactions on individual cells with nanometer resolution. In this paper, AFM peak force tapping (PFT) imaging mode was applied to rapidly locate and visually map the CD20 molecules on human lymphoma cells using biochemically sensitive tips. First, avidin-biotin system was used to test the effectiveness of using PFT imaging mode to probe the specific molecular interactions. The adhesion images obtained on avidin-coated mica using biotin-tethered tips obviously showed the recognition spots which corresponded to the avidins in the simultaneously obtained topography images. The experiments confirmed the specificity and reproducibility of the recognition results. Then, the established procedure was applied to visualize the nanoscale organization of CD20s on the surface of human lymphoma Raji cells using rituximab (a monoclonal anti-CD20 antibody)-tethered tips. The experiments showed that the recognition spots in the adhesion images corresponded to the specific CD20-rituximab interactions. The cluster sizes of CD20s on lymphoma Raji cells were quantitatively analyzed from the recognition images. Finally, under the guidance of fluorescence recognition, the established procedure was applied to cancer cells from a clinical lymphoma patient. The results showed that there were significant differences between the adhesion images obtained on cancer cells and on normal cells (red blood cell). The CD20 distributions on ten cancer cells from the patient were quantified according to the adhesion images. The experimental results demonstrate the capability of applying PFT imaging to rapidly investigate the nanoscale biophysical properties of native membrane proteins on the cell surface, which is of potential significance in developing novel biomarkers for cancer diagnosis and drug development. PMID- 27374867 TI - Anti-DFS70 antibodies detected by immunoblot methods: A reliable tool to confirm the dense fine speckles ANA pattern. AB - BACKGROUND: Autoantibodies to the DFS70 (dense fine speckles 70) protein have been identified among the antinuclear antibodies (ANA) in patients with various disorders. However, the ANA test in indirect immunofluorescence (IIF) is not a reliable method to identify anti-DFS70 antibodies. We undertook this study to evaluate the diagnostic performance of two new immunoblot methods for the detection of anti-DFS70 antibodies and to investigate whether their different DFS70 antigen composition could affect diagnostic accuracy in detecting anti DFS70 antibodies. METHODS: 62 samples showing a DFS70 staining pattern by IIF were tested by dot blot (Alphadia) and line blot (Euroimmun) methods. The dot blot method employs a truncated sequence of the DFS70 antigen (residues 349-435), while the line blot uses the full-length protein (aa 1-530). The 62 samples were previously assayed by a chemoluminescent (CLIA) method also using a truncated antigen (aa 349-435): 27 were CLIA positive and 35 were CLIA negative. 120 sera from subjects with infectious diseases were used as controls. RESULT: Both immunoblot methods were positive in the 27 IIF/CLIA positive samples; in addition, the Alphadia dot blot identified another seven DFS70 samples and the Euroimmun line blot was positive in five samples that were negative by CLIA. Among the 120 control samples, two false positives were recorded for the CLIA method, six for the Alphadia method and four for the Euroimmun method. Therefore, in this selected series of samples, sensitivity and specificity were 43.5% and 98.3% for the CLIA method, 54.8% and 95% for the dot blot and 51.6% and 96.6% for the line blot, respectively. CONCLUSIONS: Because of great inconsistency in assessing the DFS70 pattern using the ANA-IIF test, specific assays should be used to confirm anti-DFS70 antibodies. The results of this study show that there is no difference in the overall diagnostic accuracy among methods that use the truncated or the full-length DFS70 antigenic sequence and that it is likely that antibodies directed against antigens other than DFS70 may be responsible for producing a DFS70-like ANA-IIF pattern. PMID- 27374868 TI - Melatonin alleviates hyperthyroidism induced oxidative stress and neuronal cell death in hippocampus of aged female golden hamster, Mesocricetus auratus. AB - Oxidative stress is a well known phenomenon under hyperthyroid condition that induces various physiological and neural problems with a higher prevalence in females. We, therefore investigated the antioxidant potential of melatonin (Mel) on hyperthyroidism-induced oxidative stress and neuronal cell death in the hippocampus region of brain (cognition and memory centre) of aged female golden hamster, Mesocricetus auratus. Aged female hamsters were randomly divided into four experimental groups (n=7); group-I: control, group-II: Melatonin (5mgkg( 1)day(-1), i.p., for one week), group-III: Hyperthyroid (100MUg kg(-1)day(-1), i.p., for two weeks) and group-IV- Hyper+Mel. Hormonal profiles (thyroid and melatonin), activity of antioxidant enzymes (SOD, CAT and GPX), lipid peroxidation level (TBARS) and the specific apoptotic markers (Bax/Bcl-2 ratio and Caspase-3) expression were evaluated. A significant increase in the profile of total thyroid hormone (tT3 and tT4) in hyperthyroidic group as compared to control while tT3 significantly decreased in melatonin treated hyperthyroidic group. However, Mel level significantly decreased in hyperthyroidic group but increased in melatonin treated hyperthyroidic group. Further, the number of immune-positive cells for thyroid hormone receptor-alpha (TR-alpha) decreased in the hippocampus of hyperthyroidic group and increased in melatonin treated hyperthyroidic group. Profiles of antioxidant enzymes showed a significant decrease in hyperthyroidic group with a simultaneous increase in lipid peroxidation (TBARS). Melatonin treatment to hyperthyroidic group lead to decreased TBARS level with a concomitant increase in antioxidant enzyme activity. Moreover, increased expression of Bax/Bcl-2 ratio and Caspase-3, in hyperthyroidic group had elevated neuronal cell death in hippocampal area and melatonin treatment reduced its expression in hyperthyroidic group. Our findings thus indicate that melatonin reduced the hyperthyroidism-induced oxidative stress and neuronal cell death in the hippocampus region of brain, suggesting a novel therapeutic approach of melatonin for management of cognition and memory function in females under hyperthyroid condition. PMID- 27374869 TI - Resting-state functional MRI distinguishes temporal lobe epilepsy subtypes. AB - OBJECTIVE: We assessed whether presurgical resting state functional magnetic resonance imaging (fMRI) provides information for distinguishing temporal lobe epilepsy (TLE) with mesial temporal sclerosis (TLE-MTS) from TLE without MTS (TLE noMTS). METHODS: Thirty-four patients with TLE and 34 sex-/age-matched controls consented to a research imaging protocol. MTS status was confirmed by histologic evaluation of surgical tissue (TLE-MTS = 16; TLE-noMTS = 18). The fractional amplitude of low-frequency fluctuations (fALFFs) in the blood oxygen level dependent (BOLD) resting-state fMRI signal, a marker of local metabolic demand at rest, was averaged at five regions of interest (ROIs; hippocampus, amygdala, frontal, occipital, and temporal lobe), along with corresponding volume and cortical thickness estimates. ROIs were labeled ipsilateral or contralateral according to seizure lateralization and compared across TLE-MTS, TLE-noMTS, and healthy controls (HCs). MTS status was regressed on ipsilateral hippocampal volume and fALFF to test for independent contributions. RESULTS: The TLE-MTS group had reduced fALFF in the ipsilateral amygdala and hippocampus; whereas, the TLE-noMTS group had marginally reduced fALFF in the ipsilateral amygdala but not hippocampus. These results were consistently obtained with and without application of global signal regression (GSR). Ipsilateral hippocampal volume contributed to 37% of the variance in MTS status (p < 0.001) and fALFF contributed an additional 10% (p = 0.021). Two MTS cases were accurately classified with fALFF but not volume, and three were accurately classified with volume but not fALFF. At the lobar level, fALFF (with GSR) was reduced in the ipsilateral temporal and bilateral frontal lobes of patients with TLE-MTS and bilateral frontal lobes of patients with TLE-noMTS in the context of normal cortical thickness. SIGNIFICANCE: This study indicates that resting-state fMRI provides complementary functional information for MTS classification. Findings validate fALFF as a measure of regional brain integrity in TLE and highlight the value of using multi-modal imaging to provide independent diagnostic information in presurgical epilepsy evaluations. PMID- 27374871 TI - Association of thyroid-stimulating hormone with lipid concentrations: an 11-year longitudinal study. AB - BACKGROUND: Scant data exist on the longitudinal association between thyroid function and lipid concentrations. We investigated associations of TSH and lipid concentrations cross-sectionally and longitudinally in a nationwide population sample. METHODS: A total of 5205 randomly sampled participants representative of Finns aged >=30 years were examined in 2000-2001 and included in cross-sectional analyses. A total of 2486 were re-examined 11 years later and included in longitudinal analyses. With linear regression models adjusted for age, gender, smoking and body mass index, we assessed the associations of baseline TSH and TSH categories (low, reference range and high) with total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol; apolipoprotein A1 and B; and triglycerides at baseline and follow-up. RESULTS: At baseline, higher TSH associated with higher total cholesterol (beta = 0.025, standard error [SE] = 0.007, P < 0.001), LDL cholesterol (beta = 0.020, SE = 0.007, P = 0.002), apolipoprotein B (beta = 0.006, SE = 0.002, P < 0.001) and log triglycerides (beta = 0.008, SE = 0.003, P = 0.004), but not with other lipid outcomes. Higher baseline TSH associated with higher total cholesterol (beta = 0.056, SE = 0.026, P = 0.033), LDL cholesterol (beta = 0.057, SE = 0.023, P = 0.015) and apolipoprotein B (beta = 0.012, SE = 0.006, P = 0.028) at follow-up in women, but not with any lipid outcomes in men. Participants with high TSH at baseline had a 0.22 mmol/l (95% confidence interval 0.02-0.41 mmol/l) higher LDL cholesterol at follow-up (P = 0.028) than participants with TSH in the reference range (0.4-3.4 mU/l). However, exclusion of participants with high-risk baseline lipid values rendered these positive longitudinal associations nonsignificant (P >= 0.098). CONCLUSIONS: We could confirm a modest association between higher TSH and an adverse lipid profile cross-sectionally but not indisputably longitudinally. PMID- 27374870 TI - Positive Cofactor 4 (PC4) is critical for DNA repair pathway re-routing in DT40 cells. AB - PC4 is an abundant single-strand DNA binding protein that has been implicated in transcription and DNA repair. Here, we show that PC4 is involved in the cellular DNA damage response. To elucidate the role, we used the DT40 chicken B cell model, which produces clustered DNA lesions at Ig loci via the action of activation-induced deaminase. Our results help resolve key aspects of immunoglobulin diversification and suggest an essential role of PC4 in repair pathway choice. We show that PC4 ablation in gene conversion (GC)-active cells significantly disrupts GC but has little to no effect on targeted homologous recombination. In agreement, the global double-strand break repair response, as measured by gammaH2AX foci analysis, is unperturbed 16 hours post irradiation. In cells with the pseudo-genes removed (GC inactive), PC4 ablation reduced the overall mutation rate while simultaneously increasing the transversion mutation ratio. By tagging the N-terminus of PC4, gene conversion and somatic hypermutation are all but abolished even when native non-tagged PC4 is present, indicating a dominant negative effect. Our data point to a very early and deterministic role for PC4 in DNA repair pathway re-routing. PMID- 27374872 TI - Behavioral variant frontotemporal dementia: advanced disease stages and death. A step to palliative care. AB - OBJECTIVE: The aim of the present study was to gain insight into the living and care situation in advanced behavioral variant frontotemporal dementia (bvFTD), to describe symptoms and findings in advanced bvFTD, and to evaluate somatic comorbidities and circumstances of death. METHODS: Standardized interviews were conducted with family caregivers of 83 patients with bvFTD. Forty-four percent of the patients were already deceased at the time of the interview. RESULTS: At the time of the interview or death, respectively, 47% of the patients lived in a nursing home. The median time between symptom onset and nursing home admission was 5.0 +/- 5.5 years. In moderate and severe dementia stages almost all patients suffered from severe disabilities including impairment of language, gait, swallowing, and of the ability to care for themselves. Sixteen percent of the patients had got enteral tube feeding. Comorbid somatic diseases were diagnosed in 46% of the patients. Twenty-three percent of the deceased patients had been admitted into a hospital before death. Cardiovascular disease and respiratory disease, mostly pneumonia, were the most frequent causes of death. CONCLUSIONS: Advanced bvFTD is characterized by severe cognitive impairment and physical disabilities. BvFTD leads to a premature death. Our findings stress the importance of strategies that maximize patient comfort in advanced disease stages and allow for a peaceful death. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27374873 TI - Hutchinson-Gilford Progeria Syndrome: A premature aging disease caused by LMNA gene mutations. AB - Products of the LMNA gene, primarily lamin A and C, are key components of the nuclear lamina, a proteinaceous meshwork that underlies the inner nuclear membrane and is essential for proper nuclear architecture. Alterations in lamin A and C that disrupt the integrity of the nuclear lamina affect a whole repertoire of nuclear functions, causing cellular decline. In humans, hundreds of mutations in the LMNA gene have been identified and correlated with over a dozen degenerative disorders, referred to as laminopathies. These diseases include neuropathies, muscular dystrophies, lipodystrophies, and premature aging diseases. This review focuses on one of the most severe laminopathies, Hutchinson Gilford Progeria Syndrome (HGPS), which is caused by aberrant splicing of the LMNA gene and expression of a mutant product called progerin. Here, we discuss current views about the molecular mechanisms that contribute to the pathophysiology of this devastating disease, as well as the strategies being tested in vitro and in vivo to counteract progerin toxicity. In particular, progerin accumulation elicits nuclear morphological abnormalities, misregulated gene expression, defects in DNA repair, telomere shortening, and genomic instability, all of which limit cellular proliferative capacity. In patients harboring this mutation, a severe premature aging disease develops during childhood. Interestingly, progerin is also produced in senescent cells and cells from old individuals, suggesting that progerin accumulation might be a factor in physiological aging. Deciphering the molecular mechanisms whereby progerin expression leads to HGPS is an emergent area of research, which could bring us closer to understanding the pathology of aging. PMID- 27374875 TI - Application of flat panel OLED display technology for the point-of-care detection of circulating cancer biomarkers. AB - Point-of-care molecular diagnostics can provide efficient and cost-effective medical care, and they have the potential to fundamentally change our approach to global health. However, most existing approaches are not scalable to include multiple biomarkers. As a solution, we have combined commercial flat panel OLED display technology with protein microarray technology to enable high-density fluorescent, programmable, multiplexed biorecognition in a compact and disposable configuration with clinical-level sensitivity. Our approach leverages advances in commercial display technology to reduce pre-functionalized biosensor substrate costs to pennies per cm(2). Here, we demonstrate quantitative detection of IgG antibodies to multiple viral antigens in patient serum samples with detection limits for human IgG in the 10 pg/mL range. We also demonstrate multiplexed detection of antibodies to the HPV16 proteins E2, E6, and E7, which are circulating biomarkers for cervical as well as head and neck cancers. PMID- 27374874 TI - Individual and culture-level components of survey response styles: A multi-level analysis using cultural models of selfhood. AB - Variations in acquiescence and extremity pose substantial threats to the validity of cross-cultural research that relies on survey methods. Individual and cultural correlates of response styles when using 2 contrasting types of response mode were investigated, drawing on data from 55 cultural groups across 33 nations. Using 7 dimensions of self-other relatedness that have often been confounded within the broader distinction between independence and interdependence, our analysis yields more specific understandings of both individual- and culture level variations in response style. When using a Likert-scale response format, acquiescence is strongest among individuals seeing themselves as similar to others, and where cultural models of selfhood favour harmony, similarity with others and receptiveness to influence. However, when using Schwartz's (2007) portrait-comparison response procedure, acquiescence is strongest among individuals seeing themselves as self-reliant but also connected to others, and where cultural models of selfhood favour self-reliance and self-consistency. Extreme responding varies less between the two types of response modes, and is most prevalent among individuals seeing themselves as self-reliant, and in cultures favouring self-reliance. As both types of response mode elicit distinctive styles of response, it remains important to estimate and control for style effects to ensure valid comparisons. PMID- 27374876 TI - Selecting relevant and feasible measurement instruments for the revised Dutch clinical practice guideline for physical therapy in patients after stroke. AB - PURPOSE: To select relevant and feasible instruments for the revision of the Dutch clinical practice guideline for physical therapy in patients with stroke. METHODS: In this implementation study a comprehensive proposal for ICF categories and matching instruments was developed, based on reliability and validity. Relevant instruments were then selected in a consensus round by 11 knowledge brokers who were responsible for the implementation of the selected instruments. The feasibility of the selected instruments was tested by 36 physical therapists at different work settings within stroke services. Finally, instruments that were deemed relevant and feasible were included in the revised guideline. RESULTS: A total of 28 instruments were recommended for inclusion in the revised guideline. Nineteen instruments were retained from the previous guideline. Ten new instruments were tested in clinical practice, seven of which were found feasible. Two more instruments were added after critical appraisal of the set of the measurement instruments. CONCLUSIONS: The revised guideline contains 28 relevant and feasible instrument selected and tested in clinical practice by physical therapists. Further education and implementation is needed to integrate instruments in clinical practice. Further research is proposed for developing and implementing a core set of measurement instruments to be used at fixed time points to establish data registries that allow for continuous improvement of rehabilitation for stroke patients. Implications for Rehabilitation The revised Dutch Stroke Physical Therapy Guideline recommends a total of 28 instruments, that are relevant and feasible for clinical practice of physical therapist in the different settings of stroke rehabilitation. The selection of instrument in daily practice should be part of the clinical reasoning process of PTs and be tailored to individual patients' needs and the degree of priority of the affected ICF category. Suggested education strategies for further integration of instruments in of the daily practice of PTs in Stroke Rehabilitation are: 'Training on the job' and 'peer assessment in clinical situations'. PMID- 27374877 TI - Epidemiology of intra- and peri-articular structural injuries in traumatic knee joint hemarthrosis - data from 1145 consecutive knees with subacute MRI. AB - OBJECTIVE: In patients with traumatic knee distorsion and hemarthrosis, to investigate the panorama of structural injury, as visualized on magnetic resonance imaging (MRI). DESIGN: Cohort study of 1145 consecutive patients with traumatic knee distorsion who underwent MRI within median 8 days after injury. We present structural injury as visualized on MRI in relation to age, sex and activity at injury. Population based gender specific annual incidences of common structural injuries were calculated. RESULTS: The majority of injuries (72%) occurred during sports. Overall, anterior cruciate ligament (ACL) rupture was the most common structural injury (52%), followed by meniscal tear (41%) and lateral patella dislocation (LPD, 17%). Only 12% of ACL tears were isolated with meniscal tear being the most common associated injury (55%). The annual incidence of ACL injury was 77 (70-85, 95% CI) per 100,000 inhabitants with significant differences between men (91, 80-103) and women (63, 53-73). In those aged 16 years and younger, LPD was the most frequent structural injury, both in boys (39%) and girls (43%). In this age group, the annual incidence of LPD was 88 (68 113) and higher in boys (113, 81-154) than in girls (62, 39-95). CONCLUSIONS: ACL injury occurs in one out of two knees with traumatic hemarthrosis but only 12% are without concomitant structural injury. The overall rate of traumatic knee hemarthrosis and ACL injury is higher in men. In those aged 10-19 years, ACL rupture is more common among girls than boys whereas in those 16 years and younger, LPD is more common among boys than girls. PMID- 27374880 TI - Asymmetric Transfer Hydrogenation of Imines using Alcohol: Efficiency and Selectivity are Influenced by the Hydrogen Donor. AB - The influence of the alcohol, as the hydrogen donor, on the efficiency and selectivity of the asymmetric transfer hydrogenation (ATH) of imines is reported for the first time. This discovery not only leads to a highly enantioselective access to N-aryl and N-alkyl amines, but also provides new insight into the mechanism of the ATH of imines. Both experimental and computational studies provide support for the reaction pathway involving an iridium alkoxide as the reducing species. PMID- 27374879 TI - Exploring the relationship between disease-related pain and cortisol levels in women with osteoarthritis. AB - OBJECTIVES: To determine if (1) Osteoarthritis (OA)-related pain is associated with the diurnal cortisol pattern and cortisol levels; (2) the diurnal pattern of cortisol varies with severity of OA pain and (3) the association between OA pain and cortisol is mediated by daily experience variables (DEV). DESIGN: In a community-based study of changes in regional and widespread pain among women with OA, participants (n = 31) completed daily diaries and collected three saliva samples daily for 7 days. Severity of OA-related pain was assessed by the validated Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Multilevel regression analyses estimated associations between OA pain and diurnal cortisol levels and slopes, controlling for body mass index (BMI), medication use, time and day. Mediation analyses examined DEV as potential mediators of the association between OA pain and cortisol. RESULTS: The mean age was 57 years and average BMI 31 kg/m2. Mean WOMAC pain subscale score was 8.8. Women with higher WOMAC pain scores had higher cortisol throughout the day. The estimated association of WOMAC with cortisol [beta 0.083(0.02, 0.15) P = 0.009] represents a ~9% increase in cortisol for every unit increase in WOMAC pain score. Women with WOMAC pain scores >=9 had higher cortisol levels than those with scores <9. Examination of DEV revealed no significant mediated associations between these relationships at the daily level. CONCLUSION: In women with OA, disease-related pain is positively associated with cortisol production, particularly with greater pain severity. Future studies should explore biologic mediating variables between OA pain and cortisol. PMID- 27374878 TI - Differential effects of altered patterns of movement and strain on joint cell behaviour and skeletal morphogenesis. AB - OBJECTIVE: There is increasing evidence that joint shape is a potent predictor of osteoarthritis (OA) risk; yet the cellular events underpinning joint morphogenesis remain unclear. We sought to develop a genetically tractable animal model to study the events controlling joint morphogenesis. DESIGN: Zebrafish larvae were subjected to periods of flaccid paralysis, rigid paralysis or hyperactivity. Immunohistochemistry and transgenic reporters were used to monitor changes to muscle and cartilage. Finite Element Models were generated to investigate the mechanical conditions of rigid paralysis. Principal component analysis was used to test variations in skeletal morphology and metrics for shape, orientation and size were applied to describe cell behaviour. RESULTS: We show that flaccid and rigid paralysis and hypermobility affect cartilage element and joint shape. We describe differences between flaccid and rigid paralysis in regions showing high principal strain upon muscle contraction. We identify that altered shape and high strain occur in regions of cell differentiation and we show statistically significant changes to cell maturity occur in these regions in paralysed and hypermobile zebrafish. CONCLUSION: While flaccid and rigid paralysis and hypermobility affect skeletal morphogenesis they do so in subtly different ways. We show that some cartilage regions are unaffected in conditions such as rigid paralysis where static force is applied, whereas joint morphogenesis is perturbed by both flaccid and rigid paralysis; suggesting that joints require dynamic movement for accurate morphogenesis. A better understanding of how biomechanics impacts skeletal cell behaviour will improve our understanding of how foetal mechanics shape the developing joint. PMID- 27374881 TI - Antioxidant, anticancer activities and mechanistic studies of the flavone glycoside diosmin and its oxidovanadium(IV) complex. Interactions with bovine serum albumin. AB - The natural antioxidant flavonoid diosmin, found in citric fruits, showed low antioxidant properties among other flavonoids due to its structural characteristics and low cytotoxicity against lung (A549) and breast (T47D, SKBR3 and MDAMB231) cancer cell lines. The anticancer behavior has been improved by the metal complex generated with the flavonoid and the oxidovanadium(IV) ion. This new complex, [VO(dios)(OH)3]Na5.6H2O (VOdios), has been synthesized and characterized both in solid and solution states. The interaction of the metal ion through the sugar moiety of diosmin precluded the improvement of the antioxidant effects. However, the cell-killing effects tested in human lung A549 and breast T47D, SKBR3 and MDAMB231 cancer cell lines, were enhanced by complexation. The anti-proliferative effects on the human lung cancer cell line were accompanied by cellular ROS generation and an increase in cytoplasm condensation. The breast cancer cell lines did not produce caspase3/7 activation, mitochondrial potential reduction and ROS generation. Therefore, a non-apoptotic form of cell death in a caspase- and oxidative stress-independent manner has been proposed. The protein binding ability has been monitored by the quenching of tryptophan emission in the presence of the compounds using bovine serum albumin (BSA) as a model protein. Both compounds could be distributed and transported in vivo and the complex displayed stronger binding affinity and higher contributions to the hydrogen bond and van der Waals forces. PMID- 27374882 TI - Synthesis and in vitro alpha-chymotrypsin inhibitory activity of 6 chlorobenzimidazole derivatives. AB - A library of benzimidazole derivatives 1-20 were synthesized, and studied for their alpha-chymotrypsin (alpha-CT) inhibitory activity in vitro. Kinetics and molecular docking studies were performed to identify the type of inhibition. Compound 1 was found to be a good inhibitor of alpha-chymotrypsin enzyme (IC50=14.8+/-0.1MUM, Ki=16.4MUM), when compared with standard chymostatin (IC50=5.7+/-0.13MUM). Compounds 2-8, 15, 17, and 18 showed significant inhibitory activities. All the inhibitors were found to be competitive inhibitors, except compound 17, which was a mixed type inhibitor. The substituents (R) in para and ortho positions of phenyl ring B, apparently played a key role in the inhibitory potential of the series. Compounds 1-20 were also studied for their cytotoxicity profile by using 3T3 mouse fibroblast cells and compounds 3, 5, 6, 8, 12-14, 16, 17, 19, and 20 were found to be cytotoxic. Molecular docking was performed on the most active members of the series in comparison to the standard compound, chymostatin, to identify the most likely binding modes. The compounds reported here can serve as templates for further studies for new inhibitors of alpha chymotrypsin and other chymotrypsin-like serine proteases enzymes. PMID- 27374883 TI - Synthesis of Stable Nanographenes with OBO-Doped Zigzag Edges Based on Tandem Demethylation-Electrophilic Borylation. AB - A tandem demethylation-aryl borylation strategy was developed to synthesize OBO doped tetrabenzo[a,f,j,o]perylenes (namely "bistetracenes") and tetrabenzo[bc,ef,kl,no]coronenes (namely "peritetracenes"). The OBO-doped bistetracene analogues exhibited excellent stability and strong fluorescence, in contrast to the unstable all-carbon bistetracene. Single-crystal X-ray analysis for OBO-doped bistetracene revealed a twisted double [5]helicene structure, indicating that this synthesis is applicable to new heterohelicenes. Importantly, cyclodehydrogenation of the bistetracene analogues successfully produced the unprecedented heteroatom-doped peritetracenes, which opened up a new avenue to periacene-type nanographenes with stable zigzag edges. PMID- 27374885 TI - Corrigendum to "Design of a multi-arm randomized clinical trial with no control arm" [Contemporary Clinical Trials 46 (2016) 12-17]. PMID- 27374884 TI - RNA is an Adjuvanticity Mediator for the Lipid-Based Mucosal Adjuvant, Endocine. AB - Nasal vaccination has the potential to elicit systemic and mucosal immunity against pathogens. However, split and subunit vaccines lack potency at stimulating mucosal immunity, and an adjuvant is indispensable for eliciting potent mucosal immune response to nasal vaccines. Endocine, a lipid-based mucosal adjuvant, potentiates both systemic and mucosal immune responses. Although Endocine has shown efficacy and tolerability in animal and clinical studies, its mechanism of action remains unknown. It has been reported recently that endogenous danger signals are essential for the effects of some adjuvants such as alum or MF59. However, the contribution of danger signals to the adjuvanticity of Endocine has not been explored. Here, we show that RNA is likely to be an important mediator for the adjuvanticity of Endocine. Administration of Endocine generated nucleic acids release, and activated dendritic cells (DCs) in draining lymph nodes in vivo. These results suggest the possibility that Endocine indirectly activates DCs via damage-associated molecular patterns. Moreover, the adjuvanticity of Endocine disappeared in mice lacking TANK-binding kinase 1 (Tbk1), which is a downstream molecule of nucleic acid sensing signal pathway. Furthermore, co-administration of RNase A reduced the adjuvanticity of Endocine. These data suggest that RNA is important for the adjuvanticity of Endocine. PMID- 27374886 TI - Strongyloides spp. infections of veterinary importance. AB - This paper reviews the occurrence and impact of threadworms, Strongyloides spp., in companion animals and large livestock, the potential zoonotic implications and future research. Strongyloides spp. infect a range of domestic animal species worldwide and clinical disease is most often encountered in young animals. Dogs are infected with Strongyloides stercoralis while cats are infected with different species according to geographical location (Strongyloides felis, Strongyloides tumefaciens, Strongyloides planiceps and perhaps S. stercoralis). In contrast to the other species, lactogenic transmission is not a primary means of infection in dogs, and S. stercoralis is the only species considered zoonotic. Strongyloides papillosus in calves has been linked to heavy fatalities under conditions of high stocking density. Strongyloides westeri and Strongyloides ransomi of horses and pigs, respectively, cause only sporadic clinical disease. In conclusion, these infections are generally of low relative importance in livestock and equines, most likely due to extensive use of macrocyclic lactone anthelmintics and/or improved hygiene. Future prevalence studies need to include molecular typing of Strongyloides species in relation to different hosts. More research is urgently needed on the potential zoonotic capacity of Strongyloides from dogs and cats based on molecular typing, information on risk factors and mapping of transmission routes. PMID- 27374887 TI - Contents: Macromol. Rapid Commun. 13/2016. PMID- 27374889 TI - Risk Stratification for 4,837 Individuals with Knee Pain Who Receive Physical Therapy Treatment. AB - Risk stratification is a modelling method that is designed to target interventions toward patients with specific needs. The objective of the present study was to identify predictive characteristics related to patients with knee impairments who had a high risk of a bad prognosis (exceptional non-responders) as well as those who were at low risk of a bad prognosis (exceptional responders). A cohort of 4,837 patients with knee pain seen for physical therapy was retrospective analysed using univariate and multivariate multinomial regression analyses. Modelling was used to identify characteristics associated with those who were exceptional responders and those who were exceptional non responders. Exceptional non-responders were significantly associated with older age, female gender, longer duration of symptoms, surgical history, lower functional status at baseline and a payer type. Exceptional responders were significantly associated with younger age, no previous surgical history, higher functional status at baseline and a payer type. Findings may be used for managing processes involving intensity of care service and in understanding probable prognoses for each patient. Future research should continue to examine variables predictive of treatment response in patients with knee pain. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27374890 TI - Repression of the Aryl Hydrocarbon Receptor Is Required to Maintain Mitotic Progression and Prevent Loss of Pluripotency of Embryonic Stem Cells. AB - Lack of cell cycle checkpoints and uninterrupted passage through S-phase continuously renew the embryonic stem (ES) cell population and maintain pluripotency. Here, we show that to regulate mitotic progression and pluripotency ES cells must keep the aryl hydrocarbon receptor (AHR), an environmental sensor and transcriptional regulator, in a persistent state of repression. This repression, however, is not always absolute, causing the AHR to fluctuate between reversible states of expression and repression, with a fraction of the cells escaping repression at any one time. Cells that escape AHR repression exhibit reduced levels of the pluripotency factors OCT4 and SOX2 and show an extended mitotic traverse time due to AHR-dependent MID1 repression and the subsequent disruption of the MID1-PP2A-CDC25B-CDK1 signaling pathway that regulates mitosis. Unlike the bulk of the cell population that differentiates into cardiomyocytes upon stimulation, AHR-expressing ES cells restrict cardiogenesis and commit to a neuroglia cell fate. It appears that the untimely expression of the Ahr gene needs to be repressed to maintain ES cell mitotic progression and prevent premature loss of pluripotency. Stem Cells 2016;34:2825-2839. PMID- 27374891 TI - A srikaya-like light-harvesting antenna based on graphene quantum dots and porphyrin unimolecular micelles. AB - A novel hybrid light-harvesting antenna with a srikaya-like structure of multi graphene quantum dots (GQDs) as donors and one porphyrin unimolecular micelle as the acceptor was constructed through electrostatic self-assembly. The constructed antenna showed a high energy transfer efficiency of up to 93.6% and an antenna effect of 7.3 in an aqueous solution. PMID- 27374892 TI - Meta-analysis on efficacy of amoxicillin in uncomplicated severe acute malnutrition. PMID- 27374893 TI - In vivo validation of the immunogenicity of recombinant Baumannii Acinetobactin Utilization A protein (rBauA). AB - Acinetobacter baumannii has become a tremendous challenge to modern healthcare as an antimicrobial resistant. Replication and persistence of A. baumannii within eukaryotes is based on iron acquisition functions including siderophore biosynthesis. Iron transport into the cytosol is mediated by specific membrane receptors which recognize the iron-siderophore complexes. Expression of this acinetobactin mediated Iron uptake system is vital for intracellular growth of A. baumannii. Baumannii acinetobactin utilization (BauA), is an outer membrane protein, acting out the siderophore-ferric complex receptor. This study was aimed at analysis of immunogenicity and specificity of BauA. The genomic bauA was amplified via PCR method and after digestion, bauA was ligated into pET28a. The recombinant gene was expressed in Escherichia coli BL21(DE3) and the product was analyzed by SDS-PAGE and purified by Ni-NTA affinity chromatography method. The recombinant BauA (rBauA) was confirmed by western blot analysis using anti-His antibodies and its immunogenicity was assessed by injecting the rBauA to BALB/c mice. Antibodies produced therein could effectively recognize and bind rBauA. The immunized mice challenged with bacterial doses higher than LD50 survived. The antibodies were highly specific to A. baumannii and its clinical isolates. Passive immunization using serum raised against BauA protected mice from infection. BauA can be nominated as an immunogen against A. baumannii. PMID- 27374895 TI - Giving up driving: does social engagement buffer declines in mental health after driving cessation in older women? AB - Many older adults consider driving as essential to maintaining their quality of life and independence, and this may be particularly true for individuals residing in more rural areas where transportation options may be limited. Although it is normative for individuals to eventually stop driving as they age, very few plan ahead for their driving retirement (Curl et al., 2014). The process of driving cessation has been associated with a host of negative consequences for physical and mental well-being, including increased depressive symptoms, reduced network of friends, lower activity levels, and accelerated health decline (Mezuk & Rebok, 2008; Edwards et al., 2009; Curl et al., 2014). Previous studies have found that, at all ages, women are more likely to stop driving in later life than men, and often stop driving prematurely, and that various factors such as education and marital status influence the likelihood of cessation differently for women and men (Ross et al., 2009; Choi et al., 2012). Thus, factors associated with driving cessation and its consequences for older women are important to understand, particularly factors that might help buffer the negative effects of giving up driving and that might serve as early targets for preventive interventions. PMID- 27374894 TI - Biofilm production among methicillin resistant Staphylococcus aureus strains isolated from catheterized patients with urinary tract infection. AB - Between June 2011 and May 2014, we isolated a total of 419 Staphylococcus aureus strains from catheterized patients with UTI in a referral hospital in Tehran. Of these, 108 were identified as methicillin resistant (MRSA) based on their phenotypic resistance to oxacillin and the presence of mecA gene. The MRSA isolates were tested for their clonality using a combination of PFGE, prophage typing, SCCmec and ccr typing and examined for their biofilm formation as well as their resistance against 17 antibiotics. In all, 15 common pulsotypes consisted of 105 isolates and 3 single types were identified among the MRSA strains of which, 97% carried SCCmec type III and type 3 ccr. Eighty three (77%) strains were positive for biofilm formation and also carried icaA and icaD genes. Moreover, agr group III and its related tst gene were detected in 81% and 77% of biofilm producing strains, respectively 105 of the 108 MRSA were multidrug resistant with 82.4% being resistant to more than 10 antibiotics. Strains with SCCmec type IV and type 2 ccr, contained SGA and SGL prophage types, were positive for pvl gene and belonged to single PFGE types. This study highlights the important role of biofilm formation and virulence factors of MRSA strains in catheterized patients. PMID- 27374896 TI - A novel 5q11.2 microdeletion in a child with mild developmental delay and dysmorphic features. AB - 5q11.2 Deletion is a very rare genomic disorder, and its clinical phenotype has not yet been characterized. This report describes a patient with an 8.6 Mb deletion, showing hypotonia, mild developmental delay, short stature, and distinctive dysmorphic features (frontal bossing, square face, deep-set eyes, prominent columella, long philtrum, thin lips). (c) 2016 Wiley Periodicals, Inc. PMID- 27374897 TI - Perception and understanding of health claims on milk powder for children: A focus group study among mothers in Indonesia, Singapore and Thailand. AB - Health claim regulations and guidelines on food products have been established in some Southeast Asia (SEA) countries. Health claims on food products aim to help consumers make informed food choices to achieve a healthy diet. This study aimed to investigate the perception and understanding of health claims and the associated regulatory frameworks of SEA mothers using semi-structured focus groups conducted in Indonesia, Singapore and Thailand. Milk powder for children for three years and above was used as product focus. The mothers recognised and recalled some specific nutrients and food constituents by name but lacked full understanding of their function. The findings indicated that the mothers in all three countries trusted health claims made on the products which was, in part, explained by their trust in their governments and the international brand manufacturers. Their understanding of health claims was influenced by several factors such as their familiarity of the nutrient, previous knowledge of the nutrients, the perceived relevance of the nutrient, the use of scientific terms, the choice of words, and also the phrasing and length of the claims. Consumer education efforts via Public, Private Partnerships could be an approach to educate SEA consumers and help them to better understand health claims. The findings of this study may be relevant to different stakeholders such as local regulatory bodies, policy makers, food industry, academia and non-profit organisations that aim to effectively communicate health claims. PMID- 27374898 TI - A scoping review of anorexia of aging correlates and their relevance to population health interventions. AB - Anorexia of aging (AA, i.e., loss of appetite and/or reduction of food intake with aging) is an important public health issue. It leads to unintentional weight loss, which is an independent risk factor for morbidity and mortality among seniors. AA has mainly been studied from a biological perspective and regarded as a normal physiological consequence of aging, rather than a negative health outcome with underlying determinants. Some potentially modifiable correlates have however been found to be associated with this geriatric condition. Here, we conducted a scoping review of the literature to: 1) identify AA correlates, and 2) discuss their relevance to population health interventions. Our results indicate two main categories of AA correlates, namely, physiopathological and non physiopathological. The first category relates to physiological dysfunctions, pathologies involving (or culminating in) biomarker dysregulation, and polypharmacy. These correlates are difficult to modify, especially through population health interventions. The second category, which contains fewer correlates, includes potentially modifiable public health targets, such as food related properties, psychological, sociocultural, and environmental issues. We conclude that there are several AA correlates. Some of them are modifiable and could be targeted for development and implementation as appropriate population health interventions to prevent appetite loss and promote maintenance of adequate food intake in aging. PMID- 27374899 TI - Self-regulation interventions to reduce consumption of sugar-sweetened beverages in adolescents. AB - This study evaluated the efficacy of self-regulation interventions through the use of drink-specific implementation intentions and drink-specific Go/No-Go training tasks as compensatory strategies to modify inhibitory control to reduce intake of sugar-sweetened beverages (SSB). In a between-subjects randomized manipulation of implementation intentions and Go/No-Go training to learn to inhibit sugary drink consumption, 168 adolescents reporting inhibitory control problems over sugary drinks and foods were recruited from high schools in southern California to participate. Analysis of covariance overall test of effects revealed no significant differences between the groups regarding calories consumed, calories from SSBs, grams of sugar consumed from drinks, or the number of unhealthy drinks chosen. However, subsequent contrasts revealed SSB implementation intentions significantly reduced SSB consumption following intervention while controlling for inhibitory control failure and general SSB consumption during observation in a lab setting that provided SSBs and healthy drinks, as well as healthy and unhealthy snacks. Specifically, during post intervention observation, participants in the sugar-sweetened beverage implementation intentions (SSB-II) conditions consumed significantly fewer calories overall, fewer calories from drinks, and fewer grams of sugar. No effects were found for the drink-specific Go/No-Go training on SSB or calorie consumption. However, participants in SSB-II with an added SSB Go/No-Go training made fewer unhealthy drink choices than those in the other conditions. Implementation intentions may aid individuals with inhibitory (executive control) difficulties by intervening on pre-potent behavioral tendencies, like SSB consumption. PMID- 27374900 TI - Serotype, antigenicity, and pathogenicity of a naturally recombinant TW I genotype infectious bronchitis coronavirus in China. AB - Since 2009, strains of the naturally recombinant TW I genotype of infectious bronchitis virus (IBV) have caused considerable damage to the Chinese poultry industry. To better understand the antigenicity and pathogenesis of this genotype, the characteristics of the ck/CH/LDL/140520 strain were compared to those of four commercial IB vaccine strains that are used commonly in China, as well as four attenuated viruses that represent two types of IBV strains, which are believed to have originated in China and are the predominant IBV types circulating in chicken flocks in China and many other parts of the world. The results showed that all eight strains were genetically and serotypically different from the strain ck/CH/LDL/140520. Furthermore, neither the vaccine strains nor the attenuated viruses could provide complete respiratory protection of chickens against a challenge with the ck/CH/LDL/140520 strain, indicating that it is necessary to develop new live vaccines or to evaluate the use of established vaccines in combination to control naturally recombinant TW I-type IBV strains in the future. Our results showed that strain ck/CH/LDL/140520 is very pathogenic, and that it is able to cause cystic oviducts in a high percentage of birds, as well as mortality due to nephritis and respiratory distress with complete tracheal ciliostasis, especially in chickens infected at 1day of age. PMID- 27374901 TI - Genetic variability and limited clonality of Mycoplasma hyorhinis in pig herds. AB - Mycoplasma hyorhinis is a common inhabitant of the upper respiratory tract and tonsils of pigs. Its role as a possible pathogen remains controversial. In order to gain more insight into the epidemiology and population structure of M. hyorhinis we genetically characterized 60 isolates by multi locus sequence typing (MLST). The M. hyorhinis strains originated from Swiss and German pig herds with knowledge on the clinical background. The MLST scheme of Tocqueville et al. (J. Clin. Microbiol. 2014) was optimized, primers for the six MLST gene fragments were newly designed to allow amplification and sequencing with a single protocol. A total of 27 ST were observed with the 60 strains, 26 of those were previously unknown types. Generally identical genotypes were observed within a farm but they differed between farms. The identical genotype was also observed in three different Swiss farms. On the other hand different genotypes within a farm were found with three German farms. The Swiss isolates formed a distinct cluster but otherwise there was no geographical nor a clinical association with specific clusters observed. Data shows a high variability of M. hyorhinis comparable to what is observed for Mycoplasma hyopneumoniae. Similar to this pathogen the population structure of M. hyorhinis also shows some limited clonality with predominant genotypes within an animal and a single farm but different ones between farms. The comparable population structure of M. hyopneumoniae and M. hyorhinis could indicate a similar evolution of the two species in the common pig host. PMID- 27374902 TI - Brachyspira hyodysenteriae isolated from apparently healthy pig herds following an evaluation of a prototype commercial serological ELISA. AB - Swine dysentery (SD) is a disease mainly of grower/finisher pigs characterised by severe mucohaemorrhagic colitis. The classical aetiological agent is the anaerobic intestinal spirochaete Brachyspira hyodysenteriae, although "Brachyspira hampsonii" and Brachyspira suanatina also cause SD. This study reports on the unexpected isolation of B. hyodysenteriae from pigs in apparently healthy herds that gave positive reactions when tested with a prototype commercial serological ELISA for detecting herds infected with B. hyodysenteriae (Priocheck((r))Brachyspira porcine Ab ELISA). The ELISA was tested with sera collected at abattoirs from 1770 slaughtered pigs from 30 Australian herds, including 12 with a history of SD and18 that were considered by their consulting veterinarians to be healthy. The latter herds had no history of SD and did not routinely use antimicrobials that may have masked the disease. Based on the recommended ELISA cut-off value, 25 herds were recorded as showing evidence of infection, including 11 of 12 herds that were considered infected by the submitters and 14 of the 18 "healthy" herds. When faecal or colonic wall samples from 11 of the 14 "false positive" herds subsequently were culturing 6-24 months after the original ELISA testing was completed, different strains of B. hyodysenteriae were isolated from six herds, including a high-health status breeding herd. The existence of apparently healthy herds that are colonised by B. hyodysenteriae has major implications for the control of SD. Had the ELISA not been trialled it is unlikely that colonic samples from these herds would have been cultured and the colonisation identified. PMID- 27374903 TI - Induction of systemic IFITM3 expression does not effectively control foot-and mouth disease viral infection in transgenic pigs. AB - Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals, and can cause severe economic loss. Interferon-induced transmembrane (IFITM) proteins constitute a family of viral restriction factors that can inhibit the replication of several types of viruses. Our previous study showed that overexpression of swine IFITM3 (sIFITM3) impeded replication of the FMD virus (FMDV) in BHK-21 cells and mice. In this study, sIFITM3-transgenic (TG) pigs were produced by handmade cloning. Results showed that sIFITM3 was highly overexpressed in many organs of sIFITM3-TG pigs compared to wild-type pigs. After a virulent FMDV strain (O/ES/2001) was intramuscularly inoculated, the sIFITM3-TG pigs showed slightly higher susceptibility to FMDV infection than wild-type pigs. Both groups displayed comparable degrees of clinical symptoms throughout the 14 day observation period. Therefore, the induction of systemic sIFITM3 expression does not protect pigs against FMDV infection. Based on these observations, we propose that a combination of interferons and vaccines be used to control FMDV infections and subsequent FMD outbreaks. PMID- 27374904 TI - Outbreak of mortality in Russian (Acipenser gueldenstaedtii) and Siberian (Acipenser baerii) sturgeons associated with sturgeon nucleo-cytoplasmatic large DNA virus. AB - Diseased outbreaks with high mortality in farmed sturgeon are a limiting factor to the success of this emerging aquaculture sector in Europe. Thorough investigations of outbreaks can determine the aetiological agents, identify important pathological and epidemiological pathways of infections and pave the way for effective control strategies. A thorough investigation of a mortality outbreak in Russian (Acipenser gueldenstaedtii) and Siberian (Acipenser baerii) sturgeons in Italy, demonstrated the primary involvement of a sturgeon nucleo cytoplasmic large DNA virus (NCLDV). While, the taxonomy classification of this new virus is still uncertain, its involvement in sturgeon mortality outbreaks in Europe is, for the first time, fully investigated and described. Furthermore, the coinfection of bacteria such as motile Aeromonas spp. and Acinetobacter spp. was reported. Genetic characterisation showed the close relationship between the European sturgeon NCLDV with North American sturgeon NCLDVs. Similarly to the latter, the European sturgeon NCLDV persists in survivors. Furthermore, a systemic distribution of the European sturgeon NCLDV was evident in diseased A. baerii and A. gueldenstaedtii and in recovered A. gueldenstaedtii. These epidemiological and pathological findings will help in the identification of effective control strategies for sturgeon NCLDV infection, which afflicts an important and emerging European aquaculture sector. PMID- 27374905 TI - Particle and subunit-based hemagglutinin vaccines provide protective efficacy against H1N1 influenza in pigs. AB - The increasing diversity of influenza strains circulating in swine herds escalates the potential for the emergence of novel pandemic viruses and highlights the need for swift development of new vaccines. Baculovirus has proven to be a flexible platform for the generation of recombinant forms of hemagglutinin (HA) including subunit, VLP-displayed, and baculovirus-displayed antigens. These presentations have been shown to be efficacious in mouse, chicken, and ferret models but little is known about their immunogenicity in pigs. To assess the utility of these HA presentations in swine, Baculovirus constructs expressing HA fused to swine IgG2a Fc, displayed in a FeLV gag VLP, or displayed in the baculoviral envelope were generated. Vaccines formulated with these antigens wer The e administered to groups of pigs who were subsequently challenged with H1alpha cluster H1N1 swine influenza virus (SIV) A/Swine/Indiana/1726/88. Our results demonstrate that vaccination with any of these three vaccines elicits robust hemagglutinin inhibition titers in the serum and decreased the severity of SIV-associated lung lesions after challenge when compared to placebo-vaccinated controls. In addition, the number of pigs with virus detected in the lungs and nasal passages was reduced. Taken together, the results demonstrate that these recombinant approaches expressed with the baculovirus expression vector system may be viable options for development of SIV vaccines for swine. PMID- 27374906 TI - Antimicrobial susceptibility monitoring of bacterial pathogens isolated from respiratory tract infections in dogs and cats across Europe: ComPath results. AB - ComPath is a pan-European resistance monitoring programme collecting bacterial pathogens from dogs and cats. We present data for respiratory tract infection (RTI) isolates collected between 2008 and 2010. Antimicrobial minimal inhibitory concentrations (MICs) were determined and susceptibility calculated following Clinical Laboratory Standards Institute (CLSI) standards for veterinary medicine. The main pathogen from dogs was Staphylococcus intermedius Group (49/215, 22.8%) which was >90% susceptible to most antimicrobials (including oxacillin - 93.9%; 3 isolates confirmed mecA-positive) but only 59.2%, 73.5% and 87.8% susceptible to tetracycline, chloramphenicol and penicillin. Bordetella bronchiseptica (48/215, 22.3%), streptococci (36/215, 16.7%), Escherichia coli (24/215, 11.2%) and Pasteurella multocida (23/215, 10.7%) were also found in dog RTI. There are no breakpoints for Bordetella bronchiseptica. Most streptococci were penicillin- chloramphenicol-, ampicillin- and pradofloxacin-susceptible. None were enrofloxacin-resistant but 6 isolates (16.7%) were of intermediate susceptibility. The least active agent against streptococci was tetracycline (47.2% susceptible). For E. coli, 37.5% were ampicillin-susceptible but 83.3% were amoxicillin/clavulanic acid-susceptible. Only chloramphenicol showed susceptibility>90% against E. coli, with 66.7% tetracycline-susceptible and 79.2% to 87.5% susceptibility to enrofloxacin, trimethoprim-sulfamethoxazole or pradofloxacin. P. multocida were susceptible to pradofloxacin (no other breakpoints are available). The main pathogen from cats was P. multocida (82/186, 44.1%), where only pradofloxacin has breakpoints (100% susceptible). Streptococci were also collected from cats (25/186, 13.4%) and were >90% susceptible to all antimicrobials except tetracycline (36% susceptible). Most susceptibility was calculated with human-derived breakpoints and some antimicrobials had no breakpoints. Therefore predictions of clinical utility for dog and cat RTI will remain problematical unless specific breakpoints are set. PMID- 27374907 TI - The first detection and whole genome characterization of the G6P[15] group A rotavirus strain from roe deer. AB - Although rotaviruses have been detected in a variety of host species, there are only limited records of their occurrence in deer, where their role is unknown. In this study, group A rotavirus was identified in roe deer during a study of enteric viruses in game animals. 102 samples of intestinal content were collected from roe deer (56), wild boars (29), chamois (10), red deer (6) and mouflon (1), but only one sample from roe deer was positive. Following whole genome sequence analysis, the rotavirus strain D38/14 was characterized by next generation sequencing. The genotype constellation, comprising 11 genome segments, was G6 P[15]-I2-R2-C2-M2-A3-N2-T6-E2-H3. Phylogenetic analysis of the VP7 genome segment showed that the D38/14 rotavirus strain is closely related to the various G6 zoonotic rotavirus strains of bovine-like origin frequently detected in humans. In the VP4 segment, this strain showed high variation compared to that in the P[15] strain found in sheep and in a goat. This finding suggests that rotaviruses from deer are similar to those in other DS-1 rotavirus groups and could constitute a source of zoonotically transmitted rotaviruses. The epidemiological status of group A rotaviruses in deer should be further investigated. PMID- 27374908 TI - Multilocus sequence typing of Mycoplasma mycoides subsp. capri to assess its genetic variability in a contagious agalactia endemic area. AB - Mycoplasma mycoides subsp. capri (Mmc) is one of the main causative agents of caprine contagious agalactia. Besides, the absence of accurate control methods eases its dispersion between different herds within endemic areas of this disease. In this context, there is a need to implement molecular typing schemes which offer valuable information useful to establish control measures and enables the surveillance of this pathogen. The aim of this study was to assess the genetic variability of different strains of Mmc from a contagious agalactia endemic area through multilocus sequence typing (MLST). For this purpose, five house-keeping genes (fusA, glpQ, gyrB, lepA, rpoB) from 39 field isolates were analysed. These isolates were obtained from different geographic areas of Spain, between the years 2004 and 2015. The results obtained in this study suggest that the selected MLST scheme could be a useful technique to monitor the genetic variability of Mmc in endemic areas. Despite the significant differences found between the assessed field isolates, they could be classified according to their geographical origin. Moreover, it was also possible to detect genetic differences between Mmc strains coming from the same herd at the same sampling time, which may need to be taken into consideration when designing or arranging prophylactic strategies. PMID- 27374909 TI - Preliminary treatment of bovine mastitis caused by Staphylococcus aureus, with trx-SA1, recombinant endolysin of S. aureus bacteriophage IME-SA1. AB - Methicillin-resistant Staphylococcus aureus (MRSA) has become a great threat to human and animal health and there is an urgent need to develop novel antibacterial agents to control this pathogen. The objective of this study was to obtain an active recombinant endolysin from the novel bacteriophage (IME-SA1), and conduct an efficacy trial of its effectiveness against bovine mastitis. We isolated a phage that was virulent and specific for S. aureus with an optimal multiplicity of infection of 0.01. Electron microscopy revealed that IME-SA1 was a member of the family Myoviridae, with an isometric head (98nm) and a long contractile tail (200nm). Experimental lysis experiments indicated the phage had an incubation period of 20min with a burst size of 80. When host bacteria were in early exponential growth stages, a multiplicity of infection of 0.01 resulted in a complete bacterial lysis after 9h. The endolysin gene (804bp) was cloned into the pET-32a bacterial expression vector and recombinant endolysin Trx-SA1 was successfully obtained with molecular size of about 47kDa. Preliminary results of therapeutic trials in cow udders showed that Trx-SA1 could effectively control mild clinical mastitis caused by S. aureus. The endolysin Trx-SA1 might be an alternative treatment strategy for infections caused by S. aureus, including MRSA. PMID- 27374910 TI - Comparison of protection provided by type 1 and type 2 porcine reproductive and respiratory syndrome field viruses against homologous and heterologous challenge. AB - The objective of this study was to compare protection provided by type 1 and type 2 porcine reproductive and respiratory syndrome virus (PRRSV) against homologous and heterologous challenge based on clinical, virological, immunological, and pathological analysis. At 3 and 8 weeks of age, pigs were inoculated intranasally with either 3mL of tissue culture fluid containing 10(5) TCID50/mL of type 1 PRRSV or 3mL of tissue culture fluid containing 10(5) TCID50/mL of type 2 PRRSV. The homologous challenges resulted in a significant boost of the neutralizing antibodies (NA) and interferon-gamma secreting cells (IFN-gamma-SC) compared to heterologous challenges. The reduction of secondary challenging PRRSV viremia coincided with the appearance of homologous PRRSV-specific NA and IFN-gamma-SC. Homologous challenge reduced the severity of lung lesions and levels of PRRSV viremia significantly in pigs in comparison with heterologous challenge. The differences in homologous and heterologous NA and IFN-gamma-SC response may explain the differences in protection against homologous and heterologous challenge between type 1 and type 2 PRRSV. Primary challenge (immunization) with type 1 PRRSV provided protection against the secondary homologous challenge with type 1 PRRSV but failed to provide protection against the secondary heterologous challenge of type 2 PRRSV. Primary challenge with type 2 PRRSV provided protection against both the secondary homologous challenge with type 2 PRRSV and the secondary heterologous challenge with type 1 PRRSV. PMID- 27374911 TI - Molecular epidemiology of an outbreak of clinical mastitis in sheep caused by Mannheimia haemolytica. AB - The aetiology and epidemiology of outbreaks of clinical mastitis in sheep under extensive pastoral conditions are incompletely understood. The objective of this study was to conduct a detailed investigation of a clinical mastitis outbreak that affected more than 10% of 230 at-risk ewes on a sheep and grain producing property in south east Australia during drought conditions in 2009. Milk samples were collected aseptically from all affected ewes and plated on sheep blood agar for bacterial identification. M. haemolytica was isolated from 80% of the samples that yielded cultivable microorganisms and thus was the main microorganism responsible for the outbreak. Analysis of the restriction endonuclease cleavage patterns of the isolates using pulsed field gel electrophoresis revealed some evidence of clonality, suggesting the possibility of horizontal transmission, but there was also considerable diversity between the clusters of closely related isolates. Multilocus sequence typing of the M. haemolytica isolates revealed most of the isolates belonged to ST1 with no association between the PFGE and MLST fingerprints of the isolates. Resistance to neomycin, streptomycin and sulphafurazole was detected in some of the isolates, but they were all susceptible to penicillin, ampicillin, ceftiofur, amoxycillin/clavulanic acid, ciprofloxacin, tetracycline, erythromycin and trimethoprim. This is the first published record of a comparison of the strains of M. haemolytica involved in a clinical mastitis outbreak in sheep and demonstrates the importance of this pathogen in sheep production systems, particularly during adverse climatic conditions and increased stocking rate. PMID- 27374912 TI - Heavy metal and disinfectant resistance genes among livestock-associated methicillin-resistant Staphylococcus aureus isolates. AB - Livestock associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has emerged in animal production worldwide. Most LA-MRSA in Europe belong to the clonal complex (CC) 398. The reason for the LA-MRSA emergence is not fully understood. Besides antimicrobial agents used for therapy, other substances with antimicrobial activity applied in animal feed, including metal-containing compounds might contribute to their selection. Some of these genes have been found in various novel SCCmec cassettes. The aim of this study was to assess the occurrence of metal-resistance genes among a LA-S. aureus collection [n=554, including 542 MRSA and 12 methicillin-susceptible S. aureus (MSSA)] isolated from livestock and food thereof. Most LA-MRSA isolates (76%) carried at least one metal-resistance gene. Among the LA-MRSA CC398 isolates (n=456), 4.8%, 0.2%, 24.3% and 71.5% were positive for arsA (arsenic compounds), cadD (cadmium), copB (copper) and czrC (zinc/cadmium) resistance genes, respectively. In contrast, among the LA-MRSA non-CC398 isolates (n=86), 1.2%, 18.6% and 16.3% were positive for the cadD, copB and czrC genes, respectively, and none were positive for arsA. Of the LA-MRSA CC398 isolates, 72% carried one metal-resistance gene, and the remaining harboured two or more in different combinations. Differences between LA MRSA CC398 and non-CC398 were statistically significant for arsA and czrC. The czrC gene was almost exclusively found (98%) in the presence of SCCmec V in both CC398 and non-CC398 LA-MRSA isolates from different sources. Regarding the LA MSSA isolates (n=12), some (n=4) were also positive for metal-resistance genes. This study shows that genes potentially conferring metal-resistance are frequently present in LA-MRSA. PMID- 27374913 TI - Augmenting Chinese hamster genome assembly by identifying regions of high confidence. AB - Chinese hamster Ovary (CHO) cell lines are the dominant industrial workhorses for therapeutic recombinant protein production. The availability of genome sequence of Chinese hamster and CHO cells will spur further genome and RNA sequencing of producing cell lines. However, the mammalian genomes assembled using shot-gun sequencing data still contain regions of uncertain quality due to assembly errors. Identifying high confidence regions in the assembled genome will facilitate its use for cell engineering and genome engineering. We assembled two independent drafts of Chinese hamster genome by de novo assembly from shotgun sequencing reads and by re-scaffolding and gap-filling the draft genome from NCBI for improved scaffold lengths and gap fractions. We then used the two independent assemblies to identify high confidence regions using two different approaches. First, the two independent assemblies were compared at the sequence level to identify their consensus regions as "high confidence regions" which accounts for at least 78 % of the assembled genome. Further, a genome wide comparison of the Chinese hamster scaffolds with mouse chromosomes revealed scaffolds with large blocks of collinearity, which were also compiled as high-quality scaffolds. Genome scale collinearity was complemented with EST based synteny which also revealed conserved gene order compared to mouse. As cell line sequencing becomes more commonly practiced, the approaches reported here are useful for assessing the quality of assembly and potentially facilitate the engineering of cell lines. PMID- 27374914 TI - Phakomatosis pigmentovascularis type IIb: A case with Klippel-Trenaunay syndrome and extensive dermal melanocytosis as nevus of Ota, nevus of Ito and ectopic Mongolian spots. PMID- 27374916 TI - Hypertension: AT2R activation counteracts hypertension. PMID- 27374915 TI - The epidermal growth factor receptor pathway in chronic kidney diseases. AB - The epidermal growth factor receptor (EGFR) pathway has a critical role in renal development, tissue repair and electrolyte handling. Numerous studies have reported an association between dysregulation of this pathway and the initiation and progression of various chronic kidney diseases such as diabetic nephropathy, chronic allograft nephropathy and polycystic kidney disease through the promotion of renal cell proliferation, fibrosis and inflammation. In the oncological setting, compounds that target the EGFR pathway are already in clinical use or have been evaluated in clinical trials; in the renal setting, therapeutic interventions targeting this pathway by decreasing ligand availability with disintegrin and metalloproteinase inhibitors or with ligand-neutralizing antibodies, or by inhibiting receptor activation with tyrosine kinase inhibitors or monoclonal antibodies are only just starting to be explored in animal models of chronic kidney disease and in patients with autosomal dominant polycystic kidney disease. In this Review we focus on the role of the EGFR signalling pathway in the kidney under physiological conditions and during the pathophysiology of chronic kidney diseases and explore the clinical potential of interventions in this pathway to treat chronic renal diseases. PMID- 27374917 TI - Acute kidney injury: Preventing acute kidney injury through nephrotoxin management. PMID- 27374919 TI - pH affects bacterial community composition in soils across the Huashan Watershed, China. AB - To investigate soil bacterial richness and diversity and to determine the correlations between bacterial communities and soil properties, 8 soil samples were collected from the Huashan watershed in Anhui, China. Subsequently, 454 high throughput pyrosequencing and bioinformatics analyses were performed to examine the soil bacterial community compositions. The operational taxonomic unit richness of the bacterial community ranged from 3664 to 5899, and the diversity indices, including Chao1, Shannon-Wiener, and Faith's phylogenetic diversity ranged from 7751 to 15 204, 7.386 to 8.327, and 415.77 to 679.11, respectively. The 2 most dominant phyla in the soil samples were Actinobacteria and Proteobacteria. The richness and diversity of the bacterial community were positively correlated with soil pH. The Mantel test revealed that the soil pH was the dominant factor influencing the bacterial community. The positive modular structure of co-occurrence patterns at the genus level was discovered by network analysis. The results obtained in this study provide useful information that enhances our understanding of the effects of soil properties on the bacterial communities. PMID- 27374921 TI - Plenary Lecture. PMID- 27374922 TI - Award Lecture. PMID- 27374920 TI - Plasmon Modes Induced by Anisotropic Gap Opening in Au@Cu2 O Nanorods. AB - Integration of semiconductors with noble metals to form heteronanostructures can give rise to many interesting plasmonic and electronic properties. A number of such heteronanostructures have been demonstrated comprising noble metals and n type semiconductors, such as TiO2 , ZnO, SnO2 , Fe3 O4 , and CuO. In contrast, reports on heteronanostructures made of noble metals and p-type semiconductors are scarce. Cu2 O is an unintentional p-type semiconductor with unique properties. Here, the uniform coating of Cu2 O on two types of Au nanorods and systematic studies of the plasmonic properties of the resultant core-shell heteronanostructures are reported. One type of Au nanorods is prepared by seed mediated growth, and the other is obtained by oxidation of the as-prepared Au nanorods. The (Au nanorod)@Cu2 O nanostructures produced from the as-prepared nanorods exhibit two transverse plasmon peaks, whereas those derived from the oxidized nanorods display only one transverse plasmon peak. Through electrodynamic simulations the additional transverse plasmon peak is found to originate from a discontinuous gap formed at the side of the as-prepared nanorods. The existence of the gap is verified and its formation mechanism is unraveled with additional experiments. The results will be useful for designing metal-semiconductor heteronanostructures with desired plasmonic properties and therefore also for exploring plasmon-enhanced applications in photocatalysis, solar-energy harvesting, and biotechnologies. PMID- 27374918 TI - The expanding phenotypic spectra of kidney diseases: insights from genetic studies. AB - Next-generation sequencing (NGS) has led to the identification of previously unrecognized phenotypes associated with classic kidney disease genes. In addition to improving diagnostics for genetically heterogeneous diseases and enabling a faster rate of gene discovery, NGS has enabled an expansion and redefinition of nephrogenetic disease categories. Findings from these studies raise the question of whether disease diagnoses should be made on clinical grounds, on genetic evidence or a combination thereof. Here, we discuss the major kidney disease associated genes and gene categories for which NGS has expanded the phenotypic spectrum. For example, COL4A3-5 genes, which are classically associated with Alport syndrome, are now understood to also be involved in the aetiology of focal segmental glomerulosclerosis. DGKE, which is associated with nephrotic syndrome, is also mutated in patients with atypical haemolytic uraemic syndrome. We examine how a shared genetic background between diverse clinical phenotypes can provide insight into the function of genes and novel links with essential pathophysiological mechanisms. In addition, we consider genetic and epigenetic factors that contribute to the observed phenotypic heterogeneity of kidney diseases and discuss the challenges in the interpretation of genetic data. Finally, we discuss the implications of the expanding phenotypic spectra associated with kidney disease genes for clinical practice, genetic counselling and personalized care, and present our recommendations for the use of NGS-based tests in routine nephrology practice. PMID- 27374924 TI - Mini Symposium. PMID- 27374923 TI - Symposium. PMID- 27374927 TI - PCl3-C6H6 heterodimers: evidence for Ppi phosphorus bonding at low temperatures. AB - A phosphorous trichloride (PCl3)-benzene (C6H6) heterodimer was generated in a low temperature N2 matrix and was characterized using infrared spectroscopy. The structure of the heterodimer produced in the matrix isolation experiment was discerned through ab initio computations. Computations disclosed that the experimentally detected dimer is stabilized through strong non-covalent phosphorus bonded Ppi interaction, considered as a class of pnicogen bonding. This experimentally unmapped Ppi interaction so far has been reconnoitered using atoms in molecules and natural bond orbital and energy decomposition analyses. The influence of substitutions on both the PCl3 and C6H6 monomeric units of the heterodimer was subsequently examined to understand the strength of Ppi interaction as a result of these substitutions. PMID- 27374926 TI - Complementary Detection of Multiple Electrical Sources in Tissue Using Acoustoelectric Effects. AB - Accurate 3-D mapping of multiple bioelectric sources in nerve fibers with high spatial resolution is challenging for the diagnosis and treatment of a variety of neural abnormalities. Ultrasound current source density imaging exploits the acoustoelectric (AE) effect, an interaction between electrical current and acoustic pressure waves propagating through a conducting material, and has distinct advantages over conventional electrophysiology (i.e., without ultrasound) for mapping electrical current flow in tissue. Ultrasound current source density imaging and two complementary Wheatstone bridge circuits were used to simultaneously detect two separate current flows induced in tissue phantoms. It has been found that the addition and subtraction of AE signals acquired by two circuits are independent components, regardless of whether the two sources are positioned at the same or different depths. In the ultrasound field, the AE signal from the bridge circuits is stronger, with a higher signal-to-noise ratio, than without a bridge circuit. Both experimental and simulated AE images depend on the magnitude and direction of the current, as well as the geometry (shape and thickness) and location of the current sources in the ultrasound field (2.25-MHz transducer). The experimental results are consistent with simulations consisting of multiple current sources. Real-time 3-D ultrasound current source density images of multiple current flows co-registered with convention pulse echo ultrasound potentially facilitate monitoring of neurologic disorders. PMID- 27374928 TI - Halobium palmae gen. nov., sp. nov., an extremely halophilic archaeon isolated from a solar saltern. AB - A novel and extremely halophilic archaeon, designated strain 2a_47_2T, was isolated from a solar saltern sample collected in Indonesia. Cells of the strain were Gram-stain-negative, non-motile and pleomorphic and formed orange-red pigmented colonies. Strain 2a_47_2T grew at 20-48 degrees C (optimum 38-41 degrees C), pH 6.0-8.5 (optimum pH 7.5), >1.7 M NaCl (optimum 2.6 M) and <0.5 M MgCl2 (optimum 0.3 M). The major polar lipids were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, two phospholipids and sulfated diglycosyl diether. The cells mainly contained menaquinone-8. The G+C content in the genomic DNA of the strain was 67.0 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 2a_47_2T represents a member of the family Halorubraceae and is different from any other known halophilic archaea. This finding was also demonstrated by phylogenetic analyses based on deduced RpoB' amino acid sequences. Collectively, these results show that strain 2a_47_2T represents a novel genus and species in the family Halorubraceae, and the name Halobium palmae gen. nov., sp. nov. is proposed. The type strain is 2a_47_2T (=NBRC 111368T=InaCC Ar34T). PMID- 27374930 TI - Revisiting an old concept: the coupled oscillator model for VCD. Part 1: the generalised coupled oscillator mechanism and its intrinsic connection to the strength of VCD signals. AB - Motivated by the renewed interest in the coupled oscillator (CO) model for VCD, in this work a generalised coupled oscillator (GCO) expression is derived by introducing the concept of a coupled oscillator origin. Unlike the standard CO expression, the GCO expression is exact within the harmonic approximation. Using two illustrative example molecules, the theoretical concepts introduced here are demonstrated by performing a GCO decomposition of the rotational strengths computed using DFT. This analysis shows that: (1) the contributions to the rotational strengths that are normally neglected in the standard CO model can be comparable to or larger than the CO contribution, and (2) the GCO mechanism introduced here can affect the VCD intensities of all types of modes in symmetric and asymmetric molecules. PMID- 27374929 TI - Evaluation of drug provocation test-related anxiety in patients with drug hypersensitivity. AB - BACKGROUND: Drug provocation tests (DPTs) are important in the treatment of patients with drug hypersensitivity (DH), but they carry certain hypersensitivity reaction risks, which lead to procedure-related concerns in patients. OBJECTIVE: To investigate DPT-related anxiety and its effect on long-term use of tested drugs. METHODS: The study included patients who underwent DPT from July 1, 2009, to July 1, 2012. After recording the patients' history and characteristics, a variety of psychiatric (Hospital Anxiety and Depression Scale, Panic and Agoraphobia Scale, and the Maudsley Obsessive-Compulsive Inventory) and quality of-life (36-item Short Form Health Survey) tests were performed. DPT-related anxiety was also evaluated using a visual analog scale. The patients were requestioned about whether they had used the tested drug within 1 year. RESULTS: A total of 126 patients were included in the study. According to the Hospital Anxiety and Depression Scale, 23.4% and 30.6% of the patients had depression and anxiety symptoms, respectively. The mean (SD) visual analog scale anxiety scores after a negative DPT result were lower than those before DPTs (2 [2.5] after vs 5.2 [3.4] before; P < .001). In the long term, 15.9% of the patients did not use the drug because of ongoing anxiety related to drug reactions, despite negative DPT results and symptoms indicated for use of the drug. CONCLUSION: Our findings suggest that DPTs in themselves cause significant anxiety in patients with DH. Importantly, anxiety levels decreased after a negative test result. However, our results also suggested that a negative DPT result is not convincing enough for some patients to use the tested drug when needed in the future. Therefore, supporting strategies appear to be the most effective way to eliminate DH-related anxiety of patients. PMID- 27374931 TI - Histopathological implications of ventricle wall 5-aminolevulinic acid-induced fluorescence in the absence of tumor involvement on magnetic resonance images. AB - During 5-aminolevulinic acid (ALA)-guided glioblastoma multiforme (GBM) surgery, we encountered fluorescence in ventricular walls that lacked enhancement on magnetic resonance (MR) images and were free of macroscopic invasion of tumor cells. However, the meaning of ventricular wall fluorescence during 5-ALA-guided surgery is still unknown. The aim of this study was to investigate the relationship between intraoperative 5-ALA fluorescence and histopathological findings of ventricular walls free of enhancement on MR images. Nineteen patients with newly diagnosed GBM located near the lateral ventricle underwent 5-ALA fluorescence-guided surgery. During the surgery, the ventricle wall was opened and investigated with the aid of a surgical microscope equipped with optical filters to examine 5-ALA fluorescence of the ventricular wall. Twenty-five ventricular wall tissues that were apparently free of tumor involvement by MR imaging and macroscopic observation were obtained during surgery. Among the 19 cases with brightly fluorescing tumor masses, 11 patients (57.9%) exhibited 5-ALA induced fluorescence in the ventricular wall. Of the 25 ventricular wall samples, 11 exhibited 5-ALA-induced fluorescence; upon pathologic examination, tumors were present in 5 samples (45.5%), but the remaining 6 (54.5%) were free of tumor cells. A pathologic examination revealed no tumor cells in the 14 samples that lacked 5-ALA-induced fluorescence. Our data suggest the possibility that glioma cells exhibiting 5-ALA fluorescence are present in the ventricle wall, despite no signs of tumor involvement in MR images. Further investigation of non-tumor cells from tissues with 5-ALA fluorescence is needed to understand the nature of this unexpected ventricular wall fluorescence. PMID- 27374932 TI - Ictal asystole: an opportunity for pacing. PMID- 27374933 TI - Cardiac resynchronisation therapy device implantation in a patient with persistent left superior vena cava: is it still a challenge? PMID- 27374934 TI - Chronic traumatic pseudoaneurysm of the ascending aorta. PMID- 27374935 TI - Vena cava superior stenting for rescue treatment of critical stenosis related to progressing cancer disease. PMID- 27374937 TI - Absolute humidity and the human nose: A reanalysis of climate zones and their influence on nasal form and function. AB - OBJECTIVES: Investigations into the selective role of climate on human nasal variation commonly divide climates into four broad adaptive zones (hot-dry, hot wet, cold-dry, and cold-wet) based on temperature and relative humidity. Yet, absolute humidity-not relative humidity-is physiologically more important during respiration. Here, we investigate the global distribution of absolute humidity to better clarify ecogeographic demands on nasal physiology. METHODS: We use monthly observations from the Climatic Research Unit Timeseries 3 (CRU TS3) database to construct global maps of average annual temperature, relative humidity and absolute humidity. Further, using data collected by Thomson and Buxton (1923) for over 15,000 globally-distributed individuals, we calculate the actual amount of heat and water that must be transferred to inspired air in different climatic regimes to maintain homeostasis, and investigate the influence of these factors on the nasal index. RESULTS: Our results show that absolute humidity, like temperature, generally decreases with latitude. Furthermore, our results demonstrate that environments typically characterized as "cold-wet" actually exhibit low absolute humidities, with values virtually identical to cold-dry environments and significantly lower than hot-wet and even hot-dry environments. Our results also indicate that strong associations between the nasal index and absolute humidity are, potentially erroneously, predicated on individuals from hot-dry environments possessing intermediate (mesorrhine) nasal indices. DISCUSSION: We suggest that differentially allocating populations to cold-dry or cold-wet climates is unlikely to reflect different selective pressures on respiratory physiology and nasal morphology-it is cold-dry, and to a lesser degree hot-dry environments, that stress respiratory function. Our study also supports assertions that demands for inspiratory modification are reduced in hot wet environments, and that expiratory heat elimination for thermoregulation is a greater selective pressure in such environments. PMID- 27374936 TI - Analysis of Rare Variants in the Alcohol Dependence Candidate Gene GATA4. AB - BACKGROUND: Common variants in the gene GATA binding protein 4 (GATA4) show association with alcohol dependence (AD). The aim of this study was to identify rare variants in GATA4 in order to elucidate the role of this gene in AD susceptibility. Identification of rare variants may provide a more complete picture of the allelic architecture at this risk locus. METHODS: Sanger sequencing of all 6 coding exons of GATA4 was performed in 528 patients and 517 controls. Four in silico prediction tools were used to determine the effect of a DNA variant on the amino acid sequence and protein function. Five variants were included in the replication step. Of these, 4 were successfully genotyped in our replication cohort of 655 patients and 1,501 controls. All patients fulfilled DSM IV criteria for AD, and all individuals were of German descent. RESULTS: In the discovery step, 19 different heterozygous variants were identified. Four patient specific and potentially functionally relevant variants were followed up. Only the variant S379S (c.1137C>T) remained patient specific (1/1,166 patients vs. 0/1,997 controls). None of the variants showed a statistically significant association with AD. CONCLUSIONS: The present study elucidated the role of GATA4 in AD susceptibility by identifying rare variants via Sanger sequencing and subsequent replication. Although novel patient-specific rare variants of GATA4 were identified, none received support in the independent replication step. However, given previous robust findings of association with common variants, GATA4 remains a promising candidate gene for AD. PMID- 27374938 TI - Biophysical and biological perspective in biosemiotics. AB - The cell and its basic constituents are introduced here through a biophysical and information communication theoretic approach in biology and biosemiotics. With this purpose, the requirements of primordial cellular structures, single binding events, and signalling cascades are first mentioned stepwise, in relation to the model of the cellular sensing mechanism. This is followed by the concepts of cross reactions in sensing and pattern recognitions, wherein an information theoretic approach is addressed and the features of multicellularity are discussed along. Multicellularity is introduced as the path that leads to the loss of the direct causal relations. The loss of true causal relation is considered as a form of translation that enables meaning-encoded communication over the informative processes. In this sense, semiosis may not be exclusive. Synthetic biology is exemplified as a form of artificial selection mechanisms for the generation of 'self-reproducing' systems with information coding and processing machineries. These discussions are summarised at the end. PMID- 27374939 TI - Fluid bolus therapy in emergency department patients: Indications and physiological changes. AB - OBJECTIVE: The aim of the present paper is to study the indications for fluid bolus therapy (FBT) and its associated physiological changes in ED patients. METHODS: Prospective observational study of FBT in a tertiary ED, we recorded indications, number, types and volumes, resuscitation goals and perceived success rates of FBT. Moreover, we studied key physiological variables before, 10 min, 1 h and 2 h after FBT. RESULTS: We studied 500 FBT episodes (750 [500-1250] mL). Median age was 59 (36-76) years and 57% were male. Shock was deemed present in 135 (27%) patients, septic shock in 80 (16%), and cardiogenic shock in 30 (6%). Overall, 0.9% saline (84%) was the most common fluid and hypotension the most common indication (70%). 'Avoidance of hospital/ICU admission' was the goal perceived to have the greatest success rate (85%). However, although mean arterial pressure (MAP) increased (P < 0.01) and heart rate (HR) decreased (P = 0.04) at 10 min (P = 0.01), both returned to baseline at 1 and 2 h. In contrast, respiratory rate (RR) increased at 1 (P < 0.01) and 2 h (P = 0.03) and temperature decreased at 1 and 2 h (both P < 0.001). In patients with shock, 1 h after FBT, there was a median 3 mmHg increase in MAP (P = 0.01) but no change in HR (P = 0.44), while RR increased (P < 0.01) and temperature decreased (P = 0.01). CONCLUSIONS: In ED, FBT is used mostly in patients without shock. However, after an immediate haemodynamic effect, FBT is associated with absent or limited physiological changes at 1 or 2 h. Even in shocked patients, the changes in MAP at 1 or 2 h after FBT are small. PMID- 27374940 TI - Novel Au- and Ge-based two-dimensional materials formed through topotactic transitions of AlB2-like structures. AB - The topotactic reaction of a layered compound, for example CaGe2, with HCl solution is a common and facile method to produce two-dimensional (2D) materials. In this work we demonstrate with first-principles calculations that this technique can potentially lead to a whole new family of 2D materials starting from three-dimensional crystals with AlB2-like structures. As representative cases, we show here that the de-intercalation of Sc and Ca atoms from ScAuGe and Ca2AuGe3 crystals is strongly exothermic and produces the stable 2D monolayers AuGeH and AuGe3H3, respectively. Remarkably, both metals (AuGeH) and semiconductors (AuGe3H3) can be prepared by this method. Based on the broad availability of AlB2-like structures with varying stoichiometries, there are several possibilities to prepare novel functional 2D materials with suitable topotactic transitions. PMID- 27374941 TI - Does Cancer Risk in Colonic Polyps Unsuitable for Polypectomy Support the Need for Advanced Endoscopic Resections? AB - BACKGROUND: There is a continuing debate on the best approach for endoscopically benign large polyps that are unsuitable for conventional endoscopic resection. This study aimed to estimate the cancer risk in patients with endoscopically benign unresectable colonic polyps referred for surgery. STUDY DESIGN: We assessed patients with an endoscopic diagnosis of benign adenoma deemed not amenable to endoscopic removal, who underwent colectomy between 1997 and 2012. Patients with preoperative diagnoses of cancer, inherited polyposis syndrome, inflammatory bowel disease, and synchronous pathology requiring surgery were excluded. RESULTS: There were 439 patients (220 [50.1%] men; median age 67 years [range 27 to 97 years]) who underwent colectomy. Of 439 patients, 346 (79%) underwent preoperative endoscopy at our institution. Most of the polyps were located in the right colon (394 of 439, 89.7%), with the majority in the cecum (199 of 394, 45.3%). Polyp morphology was as follows: sessile (n = 252, 57.4%), pedunculated (n = 109, 24.8%), and flat (n = 78, 17.8%). Endoscopic pathology revealed high-grade dysplasia in 88 (20%) patients. Mean colonoscopic and postoperative polyp sizes were 3.0 cm (range 0.3 to 10 cm) and 2.7 cm (range 0 to 11 cm), respectively (p < 0.001). Final surgical pathology revealed cancer in 37 patients (8%). Polyp location, morphology, and histologic types were similar between the benign and malignant polyps. Cancer stages were: stage I (23 patients), stage II (11 patients), and stage III (3 patients). CONCLUSIONS: For the majority of endoscopically benign colonic polyps, an oncologic colonic resection may be unnecessary, so advanced endoscopic resection techniques or laparoscopic-assisted polypectomy should be considered. When bowel resection is needed, the resection should be performed, obeying oncologic principles and techniques. PMID- 27374942 TI - From attitude to action: What shapes attitude toward walking to/from school and how does it influence actual behaviors? AB - Walking to/from school could promote children's physical activity and help combat childhood obesity. Parental attitudes have been identified as one of the important predictors. But it is unclear what factors shape parental attitudes, and how those in turn influence children's school travel. This study addresses this gap of knowledge by examining the mediating effect of parental attitudes for the relationships between personal, social, and built environmental factors and children's walking-to/from-school behaviors. Survey data (N=2597) were collected from 20 public elementary schools in Austin, Texas, measuring students' typical school travel mode; personal, social, and built environmental factors related to walking-to/from-school; and relevant parental attitudes. The analysis was conducted in M-plus 6.11 to test the proposed conceptual framework using a structural equation model (SEM). Parental attitudes showed significant mediating effects on walking-to/from-school behaviors. Older child, positive peer influence, walkable home-to-school distance, and favorable walking environments were associated with more enjoyment and lower attitudinal barriers, and in turn increased likelihood of walking to/from school. Being Hispanic, increased car ownership, and stronger traffic safety concerns reduced enjoyment and increased attitudinal barriers, and thus decreased likelihood of walking to/from school. This study highlighted the importance of using multilevel interventions to reduce attitudinal barriers and increase enjoyment of walking to/from school. Collaborations among different stakeholders are needed to address environmental issues (e.g., safety concerns) and social factors (e.g., peer influence), while being sensitive to personal factors (e.g., age, ethnicity, and car ownership). PMID- 27374943 TI - Importance of taste, nutrition, cost and convenience in relation to diet quality: Evidence of nutrition resilience among US adults using National Health and Nutrition Examination Survey (NHANES) 2007-2010. AB - Concerns with taste, nutrition, cost, and convenience are said to be key influences on food choices. This study examined the importance of food-related attitudes in relation to diet quality using US national level data. Interactions by socioeconomic status (SES), gender and race/ethnicity were tested. Analyses of 8957 adults from National Health and Nutrition Examination Survey (NHANES 2007 2010) were conducted in 2014-15. Perceived importance of taste, nutrition, cost, and convenience in dietary choices were assessed using 4-point Likert scales. Education and family income-to-poverty ratio (FIPR) were SES indicators. Healthy Eating Index (HEI-2010), a measure of adherence to 2010 dietary guidelines, was the diet quality measure. Survey-weighted regressions examined associations between attitudes and HEI, and tested for interactions. Taste was rated as "very important" by 77.0% of the US adults, followed by nutrition (59.9%), cost (39.9%), and convenience (29.8%). However, it was the perceived importance of nutrition that most strongly predicted HEI (beta: +8.0 HEI scores among "very important" vs. "not at all important"). By contrast, greater importance for taste and convenience had a weak inverse relation with HEI (beta: -5.1 and -1.5 respectively), adjusting for SES. Significant interactions were observed by race/ethnicity, but not SES and gender. Those who prioritized nutrition during food shopping had higher-quality diets regardless of gender, education and income in the US. Certain racial/ethnic groups managed to eat healthy despite attaching importance to cost and convenience. This is the first evidence of nutrition resilience among US adults using national data, which has huge implications for nutrition interventions. PMID- 27374944 TI - Revised estimates of overdiagnosis from the Canadian National Breast Screening Study. AB - We have re-estimated overdiagnosis of breast cancer from mammography screening by age group in the Canadian National Breast Screening Study (CNBSS), a randomized screening trial. In the CNBSS, participants were recruited in 15 centers. 89,835 women were randomized with informed consent, 50,430 age 40-49 and 39,405 age 50 59. Women aged 40-49 received annual mammography and physical examination (MA+PX) versus a single physical examination and usual care in the community (UC). Women aged 50-59 received (MA+PX) versus (PX-alone) annually. Individual randomization resulted in 44 almost identically distributed demographic and risk factors. Annual compliance over the five or four scheduled screens was 86-95%. The cumulative numbers of invasive and in situ breast cancers ascertained by year during screening and subsequent follow-up to 25 years post entry to the CNBSS in the mammography arm have been compared to those in the control arm. Estimates of overdiagnosis were derived using post-screening cessation cut-off points from 1 to 20years.?Overdiagnosis of invasive breast cancer at five years post cessation of screening for women aged 40-49 was estimated to be 32%, and 16% for women aged 50-59; 20years post cessation of screening 48% for women 40-49 and 5% for those 50-59. Including ductal carcinoma in situ with invasive cancer, estimates were 41%, 25%, 55% and 16%, respectively. We conclude that approximately 30% of invasive screen-detected breast cancers in women age 40-49 were overdiagnosed, and 20% of those screen-detected in women age 50-59. Including ductal carcinoma in situ, the estimates are 40% and 30%, respectively. PMID- 27374945 TI - A park typology in the QUALITY cohort: Implications for physical activity and truncal fat among youth at risk of obesity. PMID- 27374946 TI - Can skin cancer prevention be improved through mobile technology interventions? A systematic review. AB - OBJECTIVE: Print-based health promotion interventions are being phased out to bring forth more appealing and assessable new technology applications. This review aimed to evaluate the current literature on the use of mobile text messaging and similar electronic technology interventions in the area of skin cancer prevention. METHOD: A search of studies guided by Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) was conducted on mobile technology interventions for improving skin cancer prevention in the electronic databases PubMed, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsycINFO. RESULTS: Overall, 136 articles were screened for eligibility between 2001 (earliest relevant article found) and November 2015. Eight studies fulfilled the inclusion criteria and were reviewed according to the PRISMA guidelines. Of these, five were randomised controlled trials (RCTs), two were controlled clinical trials, and one was a cohort study. Five studies used text messages as an intervention, two used mobile phone applications, and another used electronic messages via email. All studies resulted in self-reported behaviour change in at least one of their outcome measures (e.g., sunscreen application, seeking shade). CONCLUSION: While the behaviour change outcomes are promising, the lack of change in more objective measures such as sunburn indicates a need to further improve mobile phone technology-delivered interventions in order to have a greater impact on skin cancer prevention. Future studies may consider the use of objective outcome measures (e.g., sunscreen weight), electronic diaries, or behavioural outcomes in social networks. PMID- 27374947 TI - Gene expression profiling of NB4 cells following knockdown of nucleostemin using DNA microarrays. AB - Nucleostemin (NS) is mainly expressed in stem and tumor cells, and is necessary for the maintenance of their self-renewal and proliferation. Originally, NS was thought to exert its effects through inhibiting p53, while recent studies have revealed that NS is also able to function independently of p53. The present study performed a gene expression profiling analysis of p53-mutant NB4 leukeima cells following knockdown of NS in order to elucidate the p53-independent NS pathway. NS expression was silenced using lentivirus-mediated RNA interference technology, and gene expression profiling of NB4 cells was performed by DNA microarray analysis. A total of 1,953 genes were identified to be differentially expressed (fold change >=2 or <=0.5) following knockdown of NS expression. Furthermore, reverse-transcription quantitative polymerase chain reaction analysis was used to detect the expression of certain candidate genes, and the results were in agreement with the micaroarray data. Pathway analysis indicated that aberrant genes were enhanced in endoplasmic, c-Jun N-terminal kinase and mineral absorption pathways. The present study shed light on the mechanisms of the p54 independent NS pathway in NB4 cells and provided a foundation for the discovery of promising targets for the treatment of p53-mutant leukemia. PMID- 27374949 TI - Antibody-defined epitopes on HLA-DQ alleles reacting with antibodies induced during pregnancy and the design of a DQ eplet map. AB - The concept that HLA antibodies recognize epitopes is leading to new approaches of HLA matching at the epitope level. HLA-DQ plays an important role and many studies have identified structurally defined DQ epitopes specifically recognized by antibodies; they have been recorded in the International HLA Epitope Registry http://www.epregistry.com.br but the list is still incomplete. Pregnancy offers an attractive model to study antibody responses to HLA epitopes. The current analysis was done on 42 DQ-reactive post-pregnancy sera tested in binding assays with a panel of DQ heterodimers. The reactivity of 29 sera corresponded fully to the presence of antibody-verified DQA and DQB epitopes recorded in the Registry. Analysis of the remaining 13 sera led to the identification of additional antibody-defined DQB and DQA epitopes. We have designed the first version of an eplet map for DQ alleles which includes antibody-defined DQA and DQB epitopes and shows sequence positions with polymorphic residues which can be used in HLA epitology studies to identify new antibody-defined DQ epitopes. PMID- 27374948 TI - Identifying Patients With Sepsis on the Hospital Wards. AB - Sepsis contributes to up to half of all deaths in hospitalized patients, and early interventions, such as appropriate antibiotics, have been shown to improve outcomes. Most research has focused on early identification and treatment of patients with sepsis in the ED and the ICU; however, many patients acquire sepsis on the general wards. The goal of this review is to discuss recent advances in the detection of sepsis in patients on the hospital wards. We discuss data highlighting the benefits and limitations of the systemic inflammatory response syndrome (SIRS) criteria for screening patients with sepsis, such as its low specificity, as well as newly described scoring systems, including the proposed role of the quick sepsis-related organ failure assessment (qSOFA) score. Challenges specific to detecting sepsis on the wards are discussed, and future directions that use big data approaches and automated alert systems are highlighted. PMID- 27374950 TI - Effect of Vapocoolant on Pain During Peripheral Intravenous Cannulation. PMID- 27374951 TI - Resveratrol prevents pulmonary trunk remodeling but not right ventricular hypertrophy in monocrotaline-induced pulmonary hypertension. AB - Pulmonary hypertension (PAH) is characterized by abnormal vascular remodeling and increased pulmonary artery pressure which lead to right ventricular (RV) hypertrophy and heart failure. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a dietary polyphenol found in the skins and seeds of grapes, has been found to have antioxidant, anti-proliferative and anti-fibrotic effects. This study examined the effects of resveratrol on cardiac and pulmonary trunk remodeling, and common plasma markers of vascular function in rats with PAH was induced in male Sprague Dawley rats by a single subcutaneous injection of monocrotaline (MCT, 60mg/kg). Rats were treated with resveratrol (25mg/kg/day) by oral gavage daily for 21days. PAH was confirmed by the presence of increased RV/LV+septum weight, RV and lung weight. In MCT rats, total heart surface area and RV lumen area were increased without corresponding increases in total muscle area, indicating a dilation of the lumen. Pulmonary truck lumen area and thickness of the tunica media were increased by 43% and 44%, respectively, by MCT. Resveratrol had no significant effect on remodeling, although decreases of 12% and 27% were observed for overall heart area and pulmonary truck area, respectively. However, resveratrol significantly reduced the thickness of the pulmonary trunk tunica media. Plasma levels of angiotensin II, aldosterone, C-reactive protein and endothelin-1 were not altered with resveratrol. Our results indicate that daily treatment with resveratrol does not inhibit the abnormal remodeling of the RV induced by MCT, but attenuates the development of medial hypertrophy in the pulmonary trunk. PMID- 27374952 TI - Nonprescription Drugs and Self-medication-Approach and Practice to Pharmaceutical Education. PMID- 27374954 TI - Primary Care Requirements for Pharmacists-Clinical Reasoning Education at Schools of Pharmaceutical Sciences. AB - For appropriate primary care practice corresponding to the various symptoms of a patient, team medicine on that combines the expertise of physicians and other medical staff has been recommended in recent years. It results in (1) higher quality of medical care, (2) lower burden on the physician, (3) better medical safety, and (4) reduced medical expenses. In order to promote team medicine through inter-professional collaboration, the responsibilities of the medical staff need to be reviewed to expand their respective roles. The Ministry of Health, Labour and Welfare designated nine specific medical acts by pharmacists in 2010. Some acts require clinical reasoning (medical interview and physical assessment) in order to manage side effects in patients undergoing drug therapy. The new curriculum introduced in 2015 includes primary care education for pharmacists who see patients before they are seen by a physician. Because such patients are usually seen by the pharmacist on a walk-in basis, medical interview and inspection education is especially important in this situation. However, there is incongruity in the physical assessment education of prospective pharmacists among schools of pharmaceutical sciences in recent years, which tends to focus primarily on vital signs. Moreover, there is currently no consensus among physicians on the optimum range of procedures performed by a pharmacist before the patient is seen by a physician. In this presentation, the practice of primary care by pharmacists is discussed from the following perspectives: (1) target symptoms and patients, (2) clinical reasoning education at pharmaceutical schools, and (3) future issues. PMID- 27374953 TI - Non-prescription Drugs and Self-medication: Features and Subjects in Pharmaceutical Education. AB - At the time of consultation with a patient regarding OTC drugs, a pharmacist goes through the following five steps. In Step 1 information is collected, including the patient's gender, age, health condition, living situation, etc. In Step 2, upon analyzing and evaluating this collected information, the pharmacist decides whether to recommend that the patient see a medical doctor or whether an OTC drug is sufficient. In Step 3, when an OTC drug is required, the pharmacist suggests the most suitable OTC drug. In Step 4, the pharmacist provides the patient recommendations and information about the selected OTC. In Step 5, sales record entry and aftercare are performed. In these five steps, the pharmacist is making a decision on whether the consultation recommendation is required or optional; the step of making an optimal selection of an OTC drug is distinct from prescription dispensing. In many cases, at the time of OTC drug consultation, since the patient is not consulting a medical doctor, a pharmacist becomes a "first access" health professional. In this instance, the advice of a pharmacist may have a great influence on a patient's prognosis regarding the particular health challenge. Therefore, pharmacists who perform patient consultations regarding OTC drugs are required to have broad medical knowledge and communication skills. The features of consultation and information dissemination about OTC drugs by a pharmacist, and the practice and study of this subject in present-day pharmaceutical education, are described herein. PMID- 27374955 TI - Systematic Education of Self-Medication at Tokyo University of Pharmacy and Life Sciences. AB - The promotion of self-medication by pharmacies, with the aim of encouraging a patient's self-selection of proper OTC drug, is written about in the national action plan "Japan is Back". The subject of self-medication has been improved in the 2013 revised edition of "Model Core Curriculum for Pharmaceutical Education". At Tokyo University of Pharmacy and Life Sciences, the systematic education of self-medication was started from the onset of the six-year course in the third, fourth and fifth grade. We introduce here a new approach in our systematic education of self-medication. In the practice of the fourth grade, groups of around 5-6 students are formed. The pharmacy students assume various roles-of pharmacist, rater, observer, and chairman-and perform role-playing. We prepared a standardized patient (SP) showing various symptoms. The student of the role of pharmacist asks about the SP's symptoms, chooses an OTC drug suitable for the SP, and explains the OTC drug to the SP. After the role-playing, those in the roles of rater, observer, SP, and faculty give feedback to the student who played the role of pharmacist. Because we conduct this role-playing using SPs with a variety of symptoms, we can create a situation similar to a real drugstore. PMID- 27374956 TI - Self-medication Activities in a Community Pharmacy for Student Pharmacist Training. AB - Japan's Ministry of Health, Labour and Welfare published "the required function and the desired operating form of a pharmacy" and proposed that "a pharmacy should demonstrate a positive role for the promotion of self-medication". In the future, it will be indispensable to pharmacies that pharmacists play a role not only in dispensing medicine but also in serving a central health-station role in the community, including promoting the self-selection of proper OTC medications for the maintenance of health. My pharmacy in a traditional area in Tokyo carries OTC drugs, health and nursing care goods, medical supplies, etc. besides dispensing medicine by prescription. Moreover, a "sample measurement room" where a person can conduct a blood test by self-puncture was prepared in April of 2014. In addition, my pharmacy has held "health consultation meetings" for patients in collaboration with a registered dietitian, as well as "meetings for briefing sessions on how to better take or administer medicines" for parents of infants, etc. These activities have been useful to local residents in the prevention of lifestyle-related diseases and in promoting a better understanding of medicine. Moreover, on-site student trainees from schools of pharmacy are helping with planning, data collection, and explanation on the days of these meetings. For trainees from schools of pharmacy, participating in these activities is important to becoming a pharmacist trusted at the community level in the future. PMID- 27374957 TI - Issues and Prospects from the OTC Industry vis a vis Pharmaceutical Education and OTC Medicines. AB - In the amendment of the Pharmaceutical Affairs Law in 2013, a new category, Pharmacist Intervention Required Medicines (PIRM), was introduced, and other OTC medicines, which were classified after the 2006 amendment, were allowed to be sold via the Internet. Regarding PIRM, Japan's Ministry for Health, Labour and Welfare designates medicines which require special intervention by a pharmacist who explains their proper use to a patient through a face-to-face consultation, wherein the pharmacist provides guidance based on pharmaceutical knowledge and experience. This encourages consumers to approach their longer term personal healthcare with a rational knowledge of medicines, and dovetails with the direction described in "Japan is Back". Along with the 2006 amendment, an upgraded 6-year curriculum for the study of pharmacy in preparation for becoming a pharmacist was introduced. This allows student pharmacists to have more experience working in community pharmacies, thus supporting and providing pharmacists with the knowledge they need to better help the consumer to rationally use OTC medicines and self-select proper OTC medications. And this is not only restricted to OTC medicines, as there are many items sold in local pharmacies available to be utilized by the consumer with reasonable support by pharmacists. There is an expectation that the pharmacist be prepared to assist the consumer not only with prescriptions, but also with OTC medications, supplements, medical accessories, etc. using their knowledge and experience. PMID- 27374958 TI - Possibility of Pharmacist in Emergency Medical Care: To Bring Up a Familiar Pharmacist for Emergency Care by Fusing Clinical Pharmacist Activity and University Education. PMID- 27374959 TI - Involvement of Pharmacists in Medical Care in Emergency and Critical Care Centers. AB - Emergency and critical care centers provide multidisciplinary therapy for critically ill patients by centralizing the expertise and technology of many medical professionals. Because the patients' conditions vary, different drug treatments are administered along with surgery. Therefore, the role of pharmacists is important. Critically ill patients who receive high-level invasive treatment undergo physiological changes differing from their normal condition along with variable therapeutic effects and pharmacokinetics. Pharmacists are responsible for recommending the appropriate drug therapy using their knowledge of pharmacology and pharmacokinetics. Further, pharmacists need to determine the general condition of patients by understanding vital signs, blood gas analysis results, etc. It is therefore necessary to conduct consultations with physicians and nurses. The knowledge required for emergency medical treatment is not provided during systematic training in pharmaceutical education, meaning that pharmacists acquire it in the clinical setting through trial and error. To disseminate the knowledge of emergency medical care to pharmacy students, emergency care training has been started in a few facilities. I believe that medical facilities and universities need to conduct joint educational sessions on emergency medical care. Moreover, compared with other medical fields, there are fewer studies on emergency medical care. Research-oriented pharmacists must resolve this issue. This review introduces the work conducted by pharmacists for clinical student education and clinical research at the Emergency and Critical Care Center of Nihon University Itabashi Hospital and discusses future prospects. PMID- 27374960 TI - Participation of Pharmacists in Emergency Care at Outpatient Clinics with Multiple Beds. AB - A major difference in medical flow between acute and nonacute medical care is the urgency of diagnosis and treatment. In the acute medical setting, diagnosis and treatment sometimes must be done almost simultaneously. Learning clinical management in the acute-care setting can be the basis of drug therapy in other clinical settings. When infusion is performed in emergency medicine, stabilization of blood pH is achieved through kidney and lung functions. At the same time, the oxygen transport capacity is monitored using blood gas analysis. One medical intervention can lead to multiple diagnostic and treatment processes in the emergency medical field. Most pharmacists rarely have the opportunity to learn about the reasoning process in which different body functions are linked together such as heart, lung, and kidney functions when performing infusions in emergency medicine before starting to work in the clinical setting. Learning from emergency medicine can be applied to drug therapy in other clinical settings as it teaches how to link different body functions and understand the relationships between those functions and the results of medical tests. These are considered to be necessary reasoning skills to understand patients' conditions in various clinical situations, including management in intensive care and the treatment of chronic disease. Knowledge of emergency medicine can be the foundation of drug therapy in other clinical settings, for example, the meanings of vital signs. PMID- 27374961 TI - Physical Assessment Education Using Various Simulators. AB - Pharmacists are in demand not only because of their knowledge of medical therapy but also due to their skills in basic physical assessment and emergency care as medical personnel. Pharmaceutical education has developed using patient simulators in bedside training, seminars in hospital pharmacies, and physical assessment practice at the Kyushu University of Health and Welfare School of Pharmaceutical Sciences. We first explain the outline of the method to confirm basic vital signs with simulators and then demonstrate some simulations to enable the reproduction of drug misadministration/changes in condition. In addition, we check students' knowledge of and skill in the advanced objective structured clinical examination through practical examinations to test their technical ability in physical assessment. Furthermore, we conduct case study exercises in which students perform physical assessments and collect basic information on patient background. The Stan, Heart SIM, and Physico simulators are used. As examples of drug misadministration, the reproduction of asystole from fatal arrhythmia after the rapid intravenous injection of potassium preparations and ventricular fibrillation from tachycardia after an overdose of insulin are presented to student pharmacists utilizing the simulators. The simulation of anaphylactic shock and hyperglycemia is also possible as examples of changes in condition. Overall, pharmaceutical simulation education provides pharmacy students and pharmacists with experience in the types of medical treatment performed by various healthcare professionals, leading to explorations of the new roles of pharmacists in team medical care. PMID- 27374962 TI - Pharmaceutical Education Focused on Pharmacotherapy in Emergency Medical Care. AB - Pharmacists are expected to be active members of the healthcare team in emergency medicine, because many pharmaceuticals are administered to patients with life threatening conditions. However, adequate education for pharmacists and pharmacy students is not provided. The "Emergency Pharmaceutical Sciences" course was introduced for the first time in Japan by the Department of Pharmacy, Okayama University, to offer advanced education in emergency medicine and research related to critical care. We offer an emergency pharmaceutical training program with high-performance simulators and have succeeded in improving the clinical skills and confidence of pharmacy students. In this review, we introduce our activities intended to mold pharmacy students into emergency pharmacists who can contribute to emergency medicine. PMID- 27374963 TI - Social Pharmacy: Its Performance and Promise. AB - Among private Universities of Pharmacy in Japan, Kyoritsu University of Pharmacy was the first to introduce courses in social pharmacy in 1991. Social pharmacy is a discipline driven by social needs. By studying the relationship between pharmacy and society, particularly through case studies, the impact of drugs and changes in societal expectation of them, as well as through historical background studies and surveys of current trends, this discipline acts to determine the roles of pharmacists and pharmacies expected by society. Social pharmacy requires a basic knowledge of pharmaceutical science, but an understanding from economic viewpoints of the current systems and structures in which healthcare functions is important as well. Once these are understood, the goal is to identify social problems, and to create and apply models for their resolution which connect pharmacy and society. So far, social pharmacy has played an important role in training programs for community-based pharmacists essential for a hyper-aged society, for community pharmacies' health management programs aimed at promoting the health of residents, and educational programs for elementary and middle school children. PMID- 27374964 TI - Changes in Legal Aspects of Public Education about Drugs and Their Importance. AB - Requirements for education on proper use of drugs were included in the junior high school educational guideline in 2012 incorporating pharmaceutical education in the obligatory school curriculum. This move is closely related to the country's new OTC drug marketing system. The amendment of the Pharmaceutical Affairs Law (PAL) in 2013 highlighted the public's own role in "promoting proper use of drugs and other related products and making greater efforts to acquire knowledge and improve understanding of their effective and safe use". Furthermore, the Law to Amend the PAL and Pharmacists Law enforced in 2014 allowed all OTC drugs to be sold online under appropriate rules. Deregulation of online sale of OTC drugs is expected further to promote self-medication for minor illnesses and require stricter measures to ensure people's safety through their proper use. These legal amendments in recent years have made people's education about proper use of drugs one of the top priorities Japan should pursue at state level. Since 2000, the author has been offering education on drugs to early primary school children as part of their healthcare education program. In the future, dedicated education on drugs will be necessary for people of all ages including not only school children but also their guardians and elderly citizens as well. PMID- 27374965 TI - Molecular Mechanisms of Taste Disorder in Oxaliplatin-administered Rats. AB - Taste disorder is one of the adverse effects of cancer chemotherapy resulting in a loss of appetite, leading to malnutrition and a decrease in the quality of life of the patient. Oxaliplatin, a platinum anticancer drug, has a critical role in colon cancer chemotherapy and is known to induce taste disorder. Here, we evaluated the taste functions in oxaliplatin-administered rats. Among the taste receptors, expression levels of T1R2, one of the sweet receptor subunits, increased in the circumvallate papillae of the oxaliplatin-administered rats. In a brief-access test, i.e., behavioral analysis of the taste response, oxaliplatin administered rats showed a decreased response to sweet taste. However, we did not detect any differences in the plasma levels of zinc, number of taste cells, or morphology of taste buds between control and oxaliplatin-administered rats. In conclusion, the decreased response to sweet taste by oxaliplatin administration may be due to the upregulation of T1R2 expression. PMID- 27374966 TI - Protective Efficacy of the Ingestion of Mandarin Orange Containing beta Cryptoxanthin on Lipopolysaccharide-induced Acute Nephritis. AB - beta-cryptoxanthin is a common carotenoid pigment found in fruit, especially in Satsuma mandarins and in persimmons. After ingestion, beta-cryptoxanthin is distributed to and accumulates in organs, such as the liver, lung, and kidney. Recent studies have reported that because of its antioxidant defense, beta cryptoxanthin performs several important functions in the preservation of human health and in the prevention of several diseases, including cancer and osteoporosis. The present study aims to determine whether beta-cryptoxanthin has a protective effect on renal glomeruli during acute nephritis. To develop our acute nephritis mouse model, we induced kidney inflammation in mice using lipopolysaccharide. To analyze pathological changes in the renal glomeruli of these mice, tissue sections of the kidney were analyzed by hematoxylin-eosin and periodic acid-Schiff staining. In mice with acute nephritis, we observed a thickening of the basal membrane in the renal glomeruli. By ultrastructural analysis, abnormalities in the foot cells were also identified. In the beta cryptoxanthin-ingested mice, these pathological changes were decreased. Migration of urinal proteins occurred in mice with acute nephritis, but this was decreased in beta-cryptoxanthin-ingested mice, such that it correlated with the blood concentration of beta-cryptoxanthin. Furthermore, in beta-cryptoxanthin-ingested mice, both the accumulation and activation of inflammatory cells were decreased in the renal glomeruli. These results suggest that beta-cryptoxanthin ingestion may produce great improvement in acute nephritis. These findings provide new insights into beta-cryptoxanthin and its protective effect, and provide a new target for pharmacological therapy in human disease. PMID- 27374967 TI - An Attempt to Measure Presentation Skill Acquisition Using Peer and Self evaluation. AB - In six-year pharmacy education programs, humanistic education is now regarded as more important than ever, and we are working to incorporate active learning methods into a variety of subjects. Because performance evaluations are by their nature subjective, it is difficult to ensure the validity of any given assessment. Fifth-year students at Tohoku Pharmaceutical University learn case and prescription analysis in problem-based learning tutorials. As part of this curriculum, 20 presentation and discussion meetings over the course of 10 weeks are held, with approximately 100 students making presentations two or more times each. With regard to the presentation skills that students are expected to acquire, we instructed them to conduct peer evaluations and analyzed the evaluation results for 863 students conducted between 2012 and 2014. From the results, it was found that peer evaluation scores improved between the first and second evaluations for 70% to 86% of students, and furthermore that students who received lower scores in their first evaluations increased their scores correspondingly in the second. In addition, while 87% of students responded positively in the presentation skill acquisition self-evaluations conducted after the completion of the program, there was no correlation between the results of self-evaluation and peer evaluation. It was suggested that many students were able to cultivate an eye for criticism by evaluating other students and gain confidence by becoming aware of their own growth through repeated presentations. PMID- 27374968 TI - Interdisciplinary Subject "Yakugaku Nyumon" for First-year Students Constructed with Lectures and Problem-based Learning. AB - In 2013, Kobe Pharmaceutical University established "Yakugaku Nyumon", an interdisciplinary course, which consists of omnibus lectures and problem-based learning (PBL) on topics ranging from basic to clinical subjects. The themes of the PBL were original ones; "Study from package inserts of aspirin", which aimed to reinforce the contents of the interdisciplinary lectures, and "Let's think about aspirin derivatives (super-aspirin)", which aimed to engender an interest in studying pharmacy. The PBL featured questions from teachers to help with study and was therefore referred to as "question-led PBL" (Q-PBL). The Q-PBL regarding aspirin derivatives began with preparing answers to the questions for a small group discussion (SGD) as an assignment, followed by a SGD, a presentation, and peer-feedback. From an analysis of the questionnaire survey, it was found that students considered the Q-PBL satisfying and that they had achieved the 4 aims: (1) to increase the motivation to study, (2) to enhance an understanding of the relations and significance of basic and clinical sciences, (3) to comprehend the learning content, and (4) to recognize the importance of communication. The Q-PBL with assignments has two favorable points. One is that the first-year students can challenge difficult and high-level questions when they are given these as assignments. The other is that students, who are unfamiliar with SGD can engage in discussions with other students using the knowledge gained from the assignment. The introduction of omnibus lectures and Q-PBL, along with these improvements in theme, application, and review process, promises increased learning efficacy at the university. PMID- 27374969 TI - Association between Selective Beta-adrenergic Drugs and Blood Pressure Elevation: Data Mining of the Japanese Adverse Drug Event Report (JADER) Database. AB - Selective beta-adrenergic drugs are used clinically to treat various diseases. Because of imperfect receptor selectivity, beta-adrenergic drugs cause some adverse drug events by stimulating other adrenergic receptors. To examine the association between selective beta-adrenergic drugs and blood pressure elevation, we reviewed the Japanese Adverse Drug Event Reports (JADERs) submitted to the Japan Pharmaceuticals and Medical Devices Agency. We used the Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms extracted from Standardized MedDRA queries for hypertension to identify events related to blood pressure elevation. Spontaneous adverse event reports from April 2004 through May 2015 in JADERs, a data mining algorithm, and the reporting odds ratio (ROR) were used for quantitative signal detection, and assessed by the case/non-case method. Safety signals are considered significant if the ROR estimates and lower bound of the 95% confidence interval (CI) exceed 1. A total of 2021 reports were included in this study. Among the nine drugs examined, significant signals were found, based on the 95%CI for salbutamol (ROR: 9.94, 95%CI: 3.09-31.93) and mirabegron (ROR: 7.52, 95%CI: 4.89-11.55). The results of this study indicate that some selective beta-adrenergic drugs are associated with blood pressure elevation. Considering the frequency of their indications, attention should be paid to their use in elderly patients to avoid adverse events. PMID- 27374970 TI - The alveolar to arterial oxygen partial pressure difference is associated with pulmonary diffusing capacity in heart failure patients. AB - In chronic heart failure (HF), the alveolar-capillary membrane undergoes a remodeling process that negatively affects gas exchange. In case of alveolar capillary gas diffusion impairment, arterial desaturation (SaO2) is rarely observed in HF patients. At play are 3 factors: overall pulmonary diffusing capacity (assessed as lung diffusion for CO, DLCO), global O2 consumption (VO2) and alveolar (A) to arterial (a) pO2 gradient (AaDO2). In 100 consecutive stable HF patients, DLCO, resting respiratory gases and arterial blood gases were measured to determine VO2, paO2, pAO2 and AaDO2. DLCO was poorly but significantly related to AaDO2. The correlation improved after correcting AaDO2 for VO2 (p<0.001, r=0.49). Both VO2 and AaDO2 were independently associated with DLCO (p<0.001). Patients with reduced DLCO showed no differences as regards paO2 and pAO2. AaDO2/VO2 showed a higher gradient in patients with lower DLCO. AaDO2 increase and VO2 reduction allow preventing low SaO2 in HF patients with reduced DLCO. Accordingly, we suggest considering AaDO2 and VO2 combined and reporting AaDO2/VO2. PMID- 27374971 TI - Deubiquitylating enzyme, USP9X, regulates proliferation of cells of head and neck cancer lines. AB - OBJECTIVES: Truncating mutations in USP9X have been identified in oral squamous cell carcinoma patients. The aim of this study was to determine USP9X's functional role, if any, in head and neck cancer cells. MATERIALS AND METHODS: USP9X was depleted/overexpressed in head and neck cancer cell line: SCC15 (tongue), CAL27 (tongue), FaDu (pharynx) and Detroit 562 (pharynx). Cell proliferation was monitored using the CyQUANT assay, and cell cycle distribution was determined by flow cytometry. Immunoblot assays were conducted to assess protein levels. RT-qPCR was performed to determine Notch and Wnt pathway target gene expression. RESULTS: Our data showed a direct correlation between USP9X protein levels and proliferation, as well as Notch pathway activity in head and neck cancer cells. However, at least in FaDu, USP9X did not appear to regulate proliferation through the Notch pathway. Immunoblotting revealed a dramatic reduction in downstream targets of mTOR complex 1, namely total ribosomal protein (S6) and its phosphorylated form (pS6), when USP9X was depleted in FaDu cells. In contrast, in immortalized but non-tumorigenic HaCaT keratinocytes, USP9X depletion led to increase in cell proliferation, maintaining direct regulation of Notch activity. CONCLUSIONS: The functional role of USP9X was found to be context dependent. USP9X possibly promotes head and neck cancer cell proliferation through the mTOR pathway. PMID- 27374972 TI - A Porous Perchlorate-Doped Polypyrrole Nanocoating on Nickel Nanotube Arrays for Stable Wide-Potential-Window Supercapacitors. AB - A bottom-up synthetic strategy is developed to fabricate a highly porous wave superposed perchlorate-doped polypyrrole nanocoating on nickel nanotube arrays. The delicate nanostructure and the unique surface chemistry synergistically endow the obtained electrode with revealable pseudocapacitance, large operating potential window, and excellent cycling stability, which are highly promising for both asymmetric and symmetric supercapacitors. PMID- 27374973 TI - Dimethyl celecoxib sensitizes gastric cancer cells to ABT-737 via AIF nuclear translocation. AB - Gastric cancer is the fourth most common cancer in the world. The clinical applications of both chemotherapy and targeted drugs are limited because of the complexity of gastric cancer. In this study, sulforhodamine B, colony formation assay, 4',6-diamidino-2-phenylindole (DAPI) stain, flow cytometry were used to determine the in vitro cytotoxicity, apoptosis and mitochondrial membrane potential of gastric cancer AGS and HGC-27 cells before and after treatment. Real time PCR and Western blot were used to analyse the mRNA transcription and protein expression respectively. Confocal microscopy was used to determine the localization of target protein within the cells. Treatment with the combination of ABT-737 and 2,5-dimethyl-celecoxib (DMC) showed strong synergistic effect in both AGS and HGC-27 cells. Moreover, DMC would not influence the intracellular prostaglandin E2 (PGE2) level, thus lacking the toxicity profile of celecoxib. Interestingly, given the significant synergistic effect, combination treatment did not affect the protein expression of BH-3 proteins including Puma, Noxa and Bim. In combination treatment, cell apoptosis was found independent of caspase-3 activation. The translocation of apoptosis-inducing factor (AIF) from mitochondrion to nuclear was responsible for the induced apoptosis in the combination treatment. Taken together, this study provided a novel combination treatment regimen for gastric cancer. Furthermore, the existence of caspase independent apoptotic pathway induced by treatment of ABT-737 was not yet seen until combined with DMC, which shed light on an alternative mechanism involved in Bcl-2 inhibitor-induced apoptosis. PMID- 27374974 TI - Determination of nicotine in tobacco products based on mussel-inspired reduced graphene oxide-supported gold nanoparticles. AB - Polydopamine functionalized reduced graphene oxide-gold nanoparticle (PDA-RGO/Au) nanocomposites were successfully prepared by a simple and mild procedure. The PDA RGO/Au nanocomposite is successfully formed in an aqueous buffer solution (pH 8.5) without using any reducing agent. FTIR confirmed the successful coating of PDA and informed the reduction of the surface functional groups of GO. The formation of reduced GO and Au NPs was further evidenced by UV-Vis and X-ray diffraction spectroscopy. This method is environmentally friendly and highly beneficial for the mass production of graphene-noble metal based nanocomposite. The as prepared PDA-RGO/Au nanocomposite could greatly enhance the electrochemical oxidation of nicotine. We fabricated an electrochemical nicotine sensor based on the prepared PDA-RGO/Au nanocomposite. The proposed nicotine sensor showed a wide detection range from 0.05 to 500 MUM with a low detection limit of 0.015 MUM. Moreover, the proposed nicotine sensor was also successfully applied for determination nicotine content in tobacco products. PMID- 27374975 TI - Andean microrefugia: testing the Holocene to predict the Anthropocene. AB - Microrefugia are important for supporting populations during periods of unfavourable climate change and in facilitating rapid migration as conditions ameliorate. With ongoing anthropogenic climate change, microrefugia could have an important conservation value; however, a simple tool has not been developed and tested to predict which settings are microrefugial. We provide a tool based on terrain ruggedness modelling of individual catchments to predict Andean microrefugia. We tested the predictions using nine Holocene Polylepis pollen records. We used the mid-Holocene dry event, a period of peak aridity for the last 100 000 yr, as an analogue climate scenario for the near future. The results suggest that sites with high terrain rugosity have the greatest chance of sustaining mesic conditions under drier-than-modern climates. Fire is a feature of all catchments; however, an increase in fire is only recorded in settings with low rugosity. Owing to rising temperatures and greater precipitation variability, Andean ecosystems are threatened by increasing moisture stress. Our results suggest that high terrain rugosity helps to create more resilient catchments by trapping moisture through orographic rainfall and providing firebreaks that shelter forest from fire. On this basis, conservation policy should target protection and management of catchments with high terrain rugosity. PMID- 27374976 TI - Quality improvement and geographical indication of cachaca (Brazilian spirit) by using locally selected yeast strains. AB - AIMS: In order to improve the quality and to create a biological basis for obtainment of the protected denomination of origin (PDO), indigenous yeast were isolated and characterized for use in Salinas city (the Brazilian region of quality cachaca production). MATERIAL AND METHODS: Seven thousand and two hundred yeast colonies from 15 Salinas city distilleries were screened based on their fermentative behaviour and the physicochemical composition of cachaca. Molecular polymorphic analyses were performed to characterize these isolates. RESULTS: Two Saccharomyces cerevisiae strains (nos. 678 and 680) showed appropriate characteristics to use in the cachaca production: low levels of acetaldehyde and methanol, and high ethyl lactate/ethyl acetate ratio respectively. They also presented polymorphic characteristics more closely related between themselves even when compared to other strains from Salinas. CONCLUSIONS: The application of selected yeast to cachaca production can contribute for the improvement of the quality product as well as be used as a natural marker for PDO. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that the use of selected yeast strains could contribute to obtain a cachaca similar to those produced traditionally, while getting wide acceptation in the market, yet presenting more homogeneous organoleptic characteristics, and thus contributing to the PDO implementation. PMID- 27374977 TI - Recurrent episodes of isolated hemidystonia in a young adult: Dissection associated stenosis in the middle cerebral artery. PMID- 27374978 TI - MAPT haplotype diversity in multiple system atrophy. AB - INTRODUCTION: Multiple system atrophy (MSA) is a rare progressive neurodegenerative disorder. MSA was originally considered exclusively sporadic but reports of association with genes such as SNCA, COQ2 and LRRK2 have demonstrated that there is a genetic contribution to the disease. MAPT has been associated with several neurodegenerative diseases and we previously reported a protective association of the MAPT H2 haplotype with MSA in 61 pathologically confirmed cases. METHODS: In the present study, we assessed the full MAPT haplotype diversity in MSA patients using six MAPT tagging SNPs. We genotyped a total of 127 pathologically confirmed MSA cases, 86 patients with clinically diagnosed MSA and 1312 controls. RESULTS: We identified four significant association signals in our pathologically confirmed cases, two from the protective haplotypes H2 (MSA:16.2%, CONTROLS: 22.7%, p = 0.024) and H1E (MSA:3.0%, CONTROLS: 9.0%, p = 0.014), and two from the rare risk haplotypes H1x (MSA:3.7%, CONTROLS: 1.3%, p = 0.030) and H1J (MSA:3.0%, CONTROLS: 0.9%, p = 0.021). We evaluated the association of MSA subtypes with the common protective H2 haplotype and found a significant difference with controls for MSA patients with some degree of MSA-C (MSA-C or MSA-mixed), for whom H2 occurred in only 8.6% of patients in our pathologically confirmed series (P < 0.0001). CONCLUSIONS: Our findings provide further evidence that MAPT variation is associated with risk of MSA. Interestingly, our results suggest a greater effect size in the MSA-C compared to MSA-P for H2. Additional genetic studies in larger pathologically confirmed MSA series and meta-analytic studies will be needed to fully assess the role of MAPT and other genes in MSA. PMID- 27374979 TI - EVALUATION OF MAGNETIC RESONANCE IMAGING GUIDELINES FOR DIFFERENTIATION BETWEEN THORACOLUMBAR INTERVERTEBRAL DISK EXTRUSIONS AND INTERVERTEBRAL DISK PROTRUSIONS IN DOGS. AB - Four MRI variables have recently been suggested to be independently associated with a diagnosis of thoracolumbar intervertebral disk extrusion or protrusion. Midline intervertebral disk herniation, and partial intervertebral disk degeneration were associated with intervertebral disk protrusion, while presence of a single intervertebral disk herniation and disk material dispersed beyond the boundaries of the intervertebral disk space were associated with intervertebral disk extrusion. The aim of this retrospective, cross-sectional study was to determine whether using these MRI variables improves differentiation between thoracolumbar intervertebral disk extrusions and protrusions. Eighty large breed dogs with surgically confirmed thoracolumbar intervertebral disk extrusions or protrusions were included. Randomized MRI studies were presented on two occasions to six blinded observers, which were divided into three experience categories. During the first assessment, observers made a presumptive diagnosis of thoracolumbar intervertebral disk extrusion or protrusion without guidelines. During the second assessment they were asked to make a presumptive diagnosis with the aid of guidelines. Agreement was evaluated by Kappa-statistics. Diagnostic accuracy significantly improved from 70.8 to 79.6% and interobserver agreement for making a diagnosis of intervertebral disk extrusion or intervertebral disk protrusion improved from fair (kappa = 0.27) to moderate (kappa = 0.41) after using the proposed guidelines. Diagnostic accuracy was significantly influenced by degree of observer experience. Intraobserver agreement for the assessed variables ranged from fair to excellent and interobserver agreement ranged from fair to moderate. The results of this study suggest that the proposed imaging guidelines can aid in differentiating thoracolumbar intervertebral disk extrusions from protrusions. PMID- 27374980 TI - USP7/HAUSP: A SUMO deubiquitinase at the heart of DNA replication. AB - DNA replication is both highly conserved and controlled. Problematic DNA replication can lead to genomic instability and therefore carcinogenesis. Numerous mechanisms work together to achieve this tight control and increasing evidence suggests that post-translational modifications (phosphorylation, ubiquitination, SUMOylation) of DNA replication proteins play a pivotal role in this process. Here we discuss such modifications in the light of a recent article that describes a novel role for the deubiquitinase (DUB) USP7/HAUSP in the control of DNA replication. USP7 achieves this function by an unusual and novel mechanism, namely deubiquitination of SUMOylated proteins at the replication fork, making USP7 also a SUMO DUB (SDUB). This work extends previous observations of increased levels of SUMO and low levels of ubiquitin at the on-going replication fork. Here, we discuss this novel study, its contribution to the DNA replication and genomic stability field and what questions arise from this work. PMID- 27374981 TI - Characterization of a venom gland-associated rhabdovirus in the parasitoid wasp Diachasmimorpha longicaudata. AB - Parasitoid wasps reproduce by laying their eggs on or inside of a host insect, which triggers a defense response in the host insect that kills the developing wasp. To counteract the host's lethal response, some parasitoid wasps are associated with symbiotic viruses that alter host metabolism and development to promote successful development of the wasp embryo. These symbiotic viruses display a number of characteristics that differ from those of pathogenic viruses, but are poorly understood with the exception of one group, the polydnaviruses. Here, we characterize the genome of a non-polydnavirus associated with parasitoid wasps, Diachasmimorpha longicaudata rhabdovirus (DlRhV), and assess its role as a potential mutualistic virus. Our results show that the DlRhV genome contains six open reading frames (ORFs). Three ORFs show sequence homology to known viral genes and one ORF encodes a previously identified protein, called parasitism specific protein 24 (PSP24), that has been hypothesized to play a role in promoting successful parasitism by D. longicaudata. We constructed a phylogeny that shows that DlRhV is most closely related to other insect-infecting rhabdoviruses. Finally, we report that DlRhV infection does not occur in all populations of D. longicaudata, and is not required for successful parasitism. PMID- 27374982 TI - Role of adipokinetic hormone and adenosine in the anti-stress response in Drosophila melanogaster. AB - The role of adipokinetic hormone (AKH) and adenosine in the anti-stress response was studied in Drosophila melanogaster larvae and adults carrying a mutation in the Akh gene (Akh(1)), the adenosine receptor gene (AdoR(1)), or in both of these genes (Akh(1) AdoR(1) double mutant). Stress was induced by starvation or by the addition of an oxidative stressor paraquat (PQ) to food. Mortality tests revealed that the Akh(1) mutant was the most resistant to starvation, while the AdoR(1) mutant was the most sensitive. Conversely, the Akh(1) AdoR(1) double mutant was more sensitive to PQ toxicity than either of the single mutants. Administration of PQ significantly increased the Drome-AKH level in w(1118) and AdoR(1) larvae; however, this was not accompanied by a simultaneous increase in Akh gene expression. In contrast, PQ significantly increased the expression of the glutathione S-transferase D1 (GstD1) gene. The presence of both a functional adenosine receptor and AKH seem to be important for the proper control of GstD1 gene expression under oxidative stress, however, the latter appears to play more dominant role. On the other hand, differences in glutathione S-transferase (GST) activity among the strains, and between untreated and PQ-treated groups were minimal. In addition, the glutathione level was significantly lower in all untreated AKH- or AdoR-deficient mutant flies as compared with the untreated control w(1118) flies and further declined following treatment with PQ. All oxidative stress characteristics modified by mutations in Akh gene were restored or even improved by 'rescue' mutation in flies which ectopically express Akh. Thus, the results of the present study demonstrate the important roles of AKH and adenosine in the anti-stress response elicited by PQ in a D. melanogaster model, and provide the first evidence for the involvement of adenosine in the anti oxidative stress response in insects. PMID- 27374983 TI - Lysine acetylation stabilizes SP2 protein in the silkworm Bombyx mori. AB - Lysine acetylation (Kac) is a vital post-translational modification that plays an important role in many cellular processes in organisms. In the present study, the nutrient storage proteins in hemolymph were first found to be highly acetylated particularly SP2 protein, which contains 20 potential Kac sites. Further results confirmed that lysine acetylation could stabilize and up-regulate the protein level of anti-apoptosis protein SP2, thereby improving the survival of H2O2 treated BmN cells and suppressing the apoptosis induced by H2O2. The potential mechanism involved in the inhibition of ubiquitin-mediated proteasomal degradation by crosstalk between lysine acetylation and ubiquitination. Our results showed that the increase in the acetylation level by TSA could decrease the ubiquitination and improve the protein level of SP2, indicating that lysine acetylation could influence the SP2 protein level through competition between ubiquitination and the suppression of ubiquitin-mediated proteasomal degradation, thereby stabilizing the protein. SP2 is a major nutrient storage protein from hemolymph for amino acid storage and utilization. The crosstalk between lysine acetylation and ubiquitination of SP2 might imply an important role of lysine acetylation for nutrient storage and utilization in silkworm. PMID- 27374984 TI - A new technique for MR elastography of the supraspinatus muscle: A gradient-echo type multi-echo sequence. AB - Magnetic resonance elastography (MRE) can measure tissue stiffness quantitatively and noninvasively. Supraspinatus muscle injury is a significant problem among throwing athletes. The purpose of this study was to develop an MRE technique for application to the supraspinatus muscle by using a conventional magnetic resonance imaging (MRI). MRE acquisitions were performed with a gradient-echo type multi-echo MR sequence at 100Hz pneumatic vibration. A custom-designed vibration pad was used as a pneumatic transducer in order to adapt to individual shoulder shapes. In a gradient-echo type multi-echo MR sequence, without motion encoding gradient (MEG) that synchronizes with vibrations, bipolar readout gradient lobes achieved a similar function to MEG (MEG-like effect). In other words, a dedicated MRE sequence (built-in MEG) is not always necessary for MRE. In this study, 7 healthy volunteers underwent MRE. We investigated the effects of direction of the MEG-like effect and selected imaging planes on the patterns of wave propagation (wave image). The results indicated that wave images showed clear wave propagation on a condition that the direction of the MEG-like effect was nearly perpendicular to the long axis of the supraspinatus muscle, and that the imaging plane was superior to the proximal supraspinatus muscle. This limited condition might be ascribed to specific features of fibers in the supraspinatus muscle and wave reflection from the boundaries of the supraspinous fossa. The mean stiffness of the supraspinatus muscle was 10.6+/-3.17kPa. Our results demonstrated that using MRE, our method can be applied to the supraspinatus muscle by using conventional MRI. PMID- 27374985 TI - Alteration of protein prenylation promotes spermatogonial differentiation and exhausts spermatogonial stem cells in newborn mice. AB - Spermatogenesis in adulthood depends on the successful neonatal establishment of the spermatogonial stem cell (SSC) pool and gradual differentiation during puberty. The stage-dependent changes in protein prenylation in the seminiferous epithelium might be important during the first round of spermatogenesis before sexual maturation, but the mechanisms are unclear. We have previous found that altered prenylation in Sertoli cells induced spermatogonial apoptosis in the neonatal testis, resulting in adult infertility. Now we further explored the role of protein prenylation in germ cells, using a conditional deletion of geranylgeranyl diphosphate synthase (Ggpps) in embryonic stage and postmeiotic stage respectively. We observed infertility of Ggpps(-/-) Ddx4-Cre mice that displayed a Sertoli-cell-only syndrome phenotype, which resulted from abnormal spermatogonial differentiation and SSC depletion during the prepubertal stage. Analysis of morphological characteristics and cell-specific markers revealed that spermatogonial differentiation was enhanced from as early as the 7(th) postnatal day in the first round of spermatogenesis. Studies of the molecular mechanisms indicated that Ggpps deletion enhanced Rheb farnesylation, which subsequently activated mTORC1 and facilitated spermatogonial differentiation. In conclusion, the prenylation balance in germ cells is crucial for spermatogonial differentiation fate decision during the prepubertal stage, and the disruption of this process results in primary infertility. PMID- 27374987 TI - Natural history, risk factors and clinical features of primary hypogonadism in ageing men: Longitudinal Data from the European Male Ageing Study. AB - OBJECTIVE: In ageing men, the incidence and clinical significance of testosterone (T) decline accompanied by elevated luteinizing hormone (LH) are unclear. We describe the natural history, risk factors and clinical features associated with the development of biochemical primary hypogonadism (PHG, T < 10.5 nmol/l and LH>9.4U/l) in ageing men. DESIGN, PATIENTS AND MEASUREMENTS: A prospective observational cohort survey of 3,369 community-dwelling men aged 40-79 years, followed up for 4.3 years. Men were classified as incident (i) PHG (eugonadal [EUG, T >= 10.5 nmol/l] at baseline, PHG at follow-up), persistent (p) PHG (PHG at baseline and follow-up), pEUG (EUG at baseline and follow-up) and reversed (r) PHG (PHG at baseline, EUG at follow-up). Predictors and changes in clinical features associated with the development of PHG were analysed by regression models. RESULTS: Of 1,991 men comprising the analytical sample, 97.5% had pEUG, 1.1% iPHG, 1.1% pPHG and 0.3% rPHG. The incidence of PHG was 0.2%/year. Higher age (>70 years) [OR 12.48 (1.27-122.13), P = 0.030] and chronic illnesses [OR 4.24 (1.08-16.56); P = 0.038] predicted iPHG. Upon transition from EUG to PHG, erectile function, physical vigour and haemoglobin worsened significantly. Men with pPHG had decreased morning erections, sexual thoughts and haemoglobin with increased insulin resistance. CONCLUSIONS: Primary testicular failure in men is uncommon and predicted by old age and chronic illness. Some clinical features attributable to androgen deficiency, but not others, accompanied the T decline in men who developed biochemical PHG. Whether androgen replacement can improve sexual and/or physical function in elderly men with PHG merits further study. PMID- 27374988 TI - Nursing staff stress from challenging behaviour of residents with dementia: a concept analysis. AB - AIM: Provide insight into the concept of stress in the context of challenging behaviour of nursing home residents with dementia and its causes and consequences. BACKGROUND: Challenging behaviour is frequent in residents with dementia, but consequences for nursing staff are unclear. INTRODUCTION: Challenging behaviour of residents can be enervating for nurses and may lead to stress. Although stress in general is associated with negative outcomes, an overview of stress in this context would be a welcome addition to the field. METHOD: Concept analysis according to Walker and Avant. RESULTS: Identified antecedents of stress: physical and verbal aggression, conflicts, excessive demands and being unresponsive (residents), age, experience, tenure, nursing level and training (nursing staff). Defining attributes: disturbed homoeostasis and the personal appraisal of the situation. Identified consequences regard health, psychological aspects and behaviour. DISCUSSION: Intervening in the identified factors may contribute to prevention of stress in nursing staff. LIMITATIONS: Given a lack of strong empirical studies, our analysis is not based on a high level of evidence and needs to be tested. Papers from before 1990 might have been missed. CONCLUSION: The concept analysis revealed that nursing staff stress in the context of challenging behaviour may result from resident and nursing staff factors. Besides health and psychological consequences, behavioural consequences can enormously impact the well-being of residents. IMPLICATIONS: Application in daily care to support teams in influencing resident and nursing staff factors could prevent stress, for instance using behavioural management training or recruiting higher educated nursing staff. Given the increasing complexity of care, creating specialized units with specifically trained staff for different groups of people with dementia may be desirable. PMID- 27374986 TI - WONOEP appraisal: Molecular and cellular biomarkers for epilepsy. AB - Peripheral biomarkers have myriad potential uses for treatment, prediction, prognostication, and pharmacovigilance in epilepsy. To date, no single peripheral biomarker has demonstrated proven effectiveness, although multiple candidates are in development. In this review, we discuss the major areas of focus including inflammation, blood-brain barrier dysfunction, redox alterations, metabolism, hormones and growth factors. PMID- 27374989 TI - Diverse cap-binding properties of Drosophila eIF4E isoforms. AB - The majority of eukaryotic mRNAs are translated in a cap-dependent manner, which requires recognition of the mRNA 5' cap by eIF4E protein. Multiple eIF4E family members have been identified in most eukaryotic organisms. Drosophila melanogaster (Dm) has eight eIF4E related proteins; seven of them belong to Class I and one to Class II. Their biological roles with the exception of Dm eIF4E-1, Dm eIF4E-3 and Dm 4EHP, remain unknown. Here, we compare the molecular basis of Dm eIF4E's interactions with cap and eIF4G peptide by using homology modelling and fluorescence binding assays with various cap analogues. We found that despite the presence of conserved key residues responsible for cap recognition, the differences in binding different cap analogues among Class I Dm eIF4E isoforms are up to 14-fold. The highest affinity for cap analogues was observed for Dm eIF4E-3. We suggest that Dm eIF4E-3 and Dm eIF4E-5 bind the second nucleoside of the cap in an unusual manner via stacking interactions with a histidine or a phenylalanine residue, respectively. Moreover, the analysis of ternary complexes of eIF4G peptide-eIF4E-cap analogue showed cooperativity between eIF4G and cap binding only for Dm eIF4E-4, which exhibits the lowest affinity for cap analogues among all Dm eIF4Es. PMID- 27374991 TI - Mechanism of sodium chloride in promoting reduction of high-magnesium low-nickel oxide ore. AB - Sodium chloride has been proved that it is an effective promoter for the reduction of high-magnesium, low-nickel oxide ore. The aim of current work is to clarify the promotion behavior of sodium chloride in the roasting reduction process. The influence of moisture on the reduction of ore in the presence of sodium chloride is studied to get clear comprehension of promotion process. In the presence of moisture, the HCl is produced by pyrohydrolysis of sodium chloride for chlorinating nickel and iron oxides, moreover, interactions between metallic oxides and sodium chloride are also a way for chlorination at high temperature (>802 degrees C); subsequently, the metal chloride would be reduced by reductant. In the absence of moisture, the magnetic separation results show that the recoveries of iron and nickel have a significant increase; moreover, olivine structure would be destroyed gradually with the increase of roasting temperature in the action of sodium chloride, and the sodium chloride existed in high-magnesium, low-nickel oxide ore could make the NiO isolate from NiO-bearing minerals. The NiO reacts with Fe2O3 at high temperature to form NiFe2O4, which is conductive to the formation of Ni-Fe alloy during the reduction process. PMID- 27374992 TI - Muscle power is an important measure to detect deficits in muscle function in hip osteoarthritis: a cross-sectional study. AB - PURPOSE: To investigate between-leg differences in hip and thigh muscle strength and leg extensor power in patients with unilateral hip osteoarthritis. Further, to compare between-leg differences in knee extensor strength and leg extensor power between patients and healthy peers. METHODS: Seventy-two patients (60-87 years) with radiographic and symptomatic hip osteoarthritis not awaiting hip replacement and 35 healthy peers (63-82 years) were included. Hip and thigh muscle strength and leg extensor power were measured in patients and knee extensor strength and leg extensor power in healthy. RESULTS: The symptomatic extremity in patients was significantly (p < 0.05, paired t-test) weaker compared with the non-symptomatic extremity for five hip muscles (8-17%), knee extensors (11%) and leg extensor power (19%). Healthy older adults had asymmetry in knee extensor strength (6%, p < 0.05) comparable to that found in patients, but had no asymmetry in leg extensor power. CONCLUSIONS: Patients had generalized weakening of the affected lower extremity and numerically the largest asymmetry was evident for leg extensor power. In contrast, healthy peers had no asymmetry in leg extensor power. These results indicate that exercise interventions focusing on improving leg extensor power of the symptomatic lower extremity and reducing asymmetry may be beneficial for patients with hip osteoarthritis. Implications for Rehabilitation Even in patients with mild symptoms not awaiting hip replacement a generalized muscle weakening of the symptomatic lower extremity seems to be present. Between-leg differences in leg extensor power (force * velocity) appears to be relatively large (19%) in patients with unilateral hip osteoarthritis in contrast to healthy peers who show no asymmetry. Compared to muscle strength the relationship between functional performance and leg extensor power seems to be stronger, and more strongly related to power of the symptomatic lower extremity. Our results indicate that exercise interventions focusing on improving leg extensor power of the symptomatic lower extremity and reducing asymmetry may be beneficial for patients with mild symptoms not awaiting hip replacement. PMID- 27374990 TI - NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapy. AB - We survey the historical development of scientific knowledge surrounding Vitamin B3, and describe the active metabolite forms of Vitamin B3, the pyridine dinucleotides NAD+ and NADP+ which are essential to cellular processes of energy metabolism, cell protection and biosynthesis. The study of NAD+ has become reinvigorated by new understandings that dynamics within NAD+ metabolism trigger major signaling processes coupled to effectors (sirtuins, PARPs, and CD38) that reprogram cellular metabolism using NAD+ as an effector substrate. Cellular adaptations include stimulation of mitochondrial biogenesis, a process fundamental to adjusting cellular and tissue physiology to reduced nutrient availability and/or increased energy demand. Several mammalian metabolic pathways converge to NAD+, including tryptophan-derived de novo pathways, nicotinamide salvage pathways, nicotinic acid salvage and nucleoside salvage pathways incorporating nicotinamide riboside and nicotinic acid riboside. Key discoveries highlight a therapeutic potential for targeting NAD+ biosynthetic pathways for treatment of human diseases. A recent emergence of understanding that NAD+ homeostasis is vulnerable to aging and disease processes has stimulated testing to determine if replenishment or augmentation of cellular or tissue NAD+ can have ameliorative effects on aging or disease phenotypes. This experimental approach has provided several proofs of concept successes demonstrating that replenishment or augmentation of NAD+ concentrations can provide ameliorative or curative benefits. Thus NAD+ metabolic pathways can provide key biomarkers and parameters for assessing and modulating organism health. PMID- 27374993 TI - Dissecting Bottromycin Biosynthesis Using Comparative Untargeted Metabolomics. AB - Bottromycin A2 is a structurally unique ribosomally synthesized and post translationally modified peptide (RiPP) that possesses potent antibacterial activity towards multidrug-resistant bacteria. The structural novelty of bottromycin stems from its unprecedented macrocyclic amidine and rare beta methylated amino acid residues. The N-terminus of a precursor peptide (BtmD) is converted into bottromycin A2 by tailoring enzymes encoded in the btm gene cluster. However, little was known about key transformations in this pathway, including the unprecedented macrocyclization. To understand the pathway in detail, an untargeted metabolomic approach that harnesses mass spectral networking was used to assess the metabolomes of a series of pathway mutants. This analysis has yielded key information on the function of a variety of previously uncharacterized biosynthetic enzymes, including a YcaO domain protein and a partner protein that together catalyze the macrocyclization. PMID- 27374994 TI - Development of Collateral Pathways in Tumor Obstruction of Confluence of the Hepatic Veins: Neither Fortuitous nor Innocuous. AB - BACKGROUND: Except in Budd-Chiari syndrome, alternative drainage pathways have been described rarely. The aim was to describe the alternative collaterals pathways due to tumor hepatic vein (HV) confluence obstruction and its impact in the setting of liver resection. STUDY DESIGN: Between 2006 and 2014, preoperative CT scans of 41 patients resected for malignant tumor(s) compressing the HV confluence were assessed for the presence of accessory veins and collateral veins. A 2:1 matched control group was used for comparison of intraoperative outcomes. RESULTS: Intrahepatic collaterals were observed in 28 (68%) patients, mostly between segments 3/4b and 5/4b, and subcapsular collaterals were observed in 12 (29%) patients. Patients with isolated right HV obstruction and with an accessory right HV present had fewer collateral pathways develop than patients without (6 of 10 patients [60%] vs 18 of 19 [95%]; p = 0.036). Segment 1 hypertrophy was present in only 6 (15%) patients. Compared with the control group, there was a significant increase in blood loss (900 mL [range 100 to 3,500 mL] vs 500 mL [range 100 to 2,600 mL]; p < 0.001), transfusion requirements (71% vs 15%; p < 0.001), and vascular clamping (hepatic pedicle: 85% vs 72%; p < 0.001, inferior vena cava: 41% vs 11%; p < 0.001) in case of HV obstruction. CONCLUSIONS: Development of collateral pathways is not fortuitous and depends on the number of HVs involved and pre-existing accessory veins. The increased blood loss observed in patients with collaterals leads to consider specific vascular clamping. PMID- 27374995 TI - Women in Surgery: A History of Adversity, Resilience, and Accomplishment. PMID- 27374996 TI - The effectiveness of neurofeedback on cognitive functioning in patients with Alzheimer's disease: Preliminary results. AB - OBJECTIVES: Alzheimer's disease (AD) is the most common form of dementia. In quantified EEG (qEEG), the AD patients have a greater amount of theta activity compared with normal elderly individuals. Little is known about the effect of neurofeedback in patients with dementia. The objective of this study was to examine whether neurofeedback has a positive effect on cognitive performance in patients with AD. METHODS: Ten patients with qEEG meeting criteria for AD received neurofeedback training. Participants were aged between 61 and 90 years. All patients underwent the CAMCOG test designed to assess cognitive functioning pre- and post-treatment. RESULTS: The individual results, analyzed with a reliable change index (RCI), showed that patients who received neurofeedback treatment had stable cognitive functions. These patients showed improvement in memory after neurofeedback and other cognitive functions were stable. In addition, an improvement was observed in recall of information and recognition. CONCLUSION: Patients with AD who received neurofeedback treatment had stable or improved cognitive performance. Future research should focus on the design of high quality randomized controlled trials to assess whether neurofeedback has a place in the treatment of AD. PMID- 27374997 TI - Comparative Study of Carbon Materials Synthesized "Greenly" for 2-CP Removal. AB - Carbon nanotubes (CNTs), graphene (GA) and carbon nanospheres (CNSs) were prepared respectively using grass (Festucaarundinace) as the sole carbon resource by solvothermal method and characterized as adsorbent and photocatalyst for 2 chlorophenol (2-CP) removal in water. With H2O2/HNO3/H2SO4, the CNTs were firstly produced from grass (Festucaarundinace) at 300 degrees C by hydrolysis and oxidization, the CNTs were secondly opened to form the GA by oxidization at 400 degrees C, and the GA was lastly rolled-up to form the CNSs by oxidization at 500 degrees C. All adsorption equilibration of the CNTs, GA, and CNSs for 2-CP were achieved within 120 min, and 60.35%, 20.12%, and 76.22% of 2-CP (5 mg L(-1), pH = 6.3) were adsorbed, respectively. Furthermore, the high removal rates of 2-CP were about 88.23%, 92.90%, and 79.64% by the CNTs, GA, and CNSs, after 120 min adsorption and 160 min irradiation. On the basis of these results, the CNSs were suitable for removal 2-CP as adsorbent, and the GA was suitable as photocatalyst. The photooxidation of 2-CP was mainly initiated by O2(.-) or .OH which was generated from the combine with simulated sunlight and the CNTs or GA, respectively. However, the CNTs was not suitable for removal 2-CP owing to the increasing toxicity. PMID- 27374998 TI - Prioritizing interventions to manage polypharmacy in Australian aged care facilities. AB - BACKGROUND: Polypharmacy is highly prevalent in residential aged care facilities (RACFs). Although polypharmacy is sometimes unavoidable, polypharmacy has been associated with increased morbidity and mortality. OBJECTIVE: To identify and prioritize a range of potential interventions to manage polypharmacy in RACFs from the perspectives of health care professionals, health policy and consumer representatives. METHODS: Two nominal group technique (NGT) sessions were convened in August 2015. A purposive sample (n = 19) of clinicians, researchers, managers and representatives of consumer, professional and health policy organizations were asked to nominate interventions to address the prevalence and appropriateness of medication use. Participants were then asked to prioritize five interventions suitable for possible implementation at the system level. RESULTS: Six of 16 potential interventions were prioritized highest for possible implementation in clinical practice, with two interventions prioritized as second highest. The top interventions in rank order were 'implementation of a pharmacist led medication reconciliation service for new residents,' 'conduct facility-level audits and feedback to staff and health care professionals,' 'develop deprescribing scripts to assist clinician-resident discussion,' 'develop or revise prescribing guidelines specific to older people with multimorbidity in RACFs,' 'implement electronic medication charts and records' and 'better support Medication Advisory Committees (MACs) to address medication appropriateness.' CONCLUSION: This study prioritized a range of potential interventions that may be used to assist clinicians and policy makers develop a comprehensive strategy to manage polypharmacy in RACFs. PMID- 27375000 TI - Variations in the recruitment of syntactic knowledge contribute to SES differences in syntactic development* - ERRATUM. PMID- 27374999 TI - Oligo(lactic acid)n-Paclitaxel Prodrugs for Poly(ethylene glycol)-block poly(lactic acid) Micelles: Loading, Release, and Backbiting Conversion for Anticancer Activity. AB - Poly(ethylene glycol)-block-poly(d,l-lactic acid) (PEG-b-PLA) micelles are nanocarriers for poorly water-soluble anticancer agents and have advanced paclitaxel (PTX) to humans due to drug solubilization, biocompatibility, and dose escalation. However, PEG-b-PLA micelles rapidly release PTX, resulting in widespread biodistribution and low tumor exposure. To improve delivery of PTX by PEG-b-PLA micelles, monodisperse oligo(l-lactic acid), o(LA)8 or o(LA)16, has been coupled onto PTX at the 7-OH position, forming ester prodrugs: o(LA)8-PTX and o(LA)16-PTX, respectively. As expected, o(LA)n-PTX was more compatible with PEG-b-PLA micelles than PTX, increasing drug loading from 11 to 54%. While in vitro release of PTX was rapid, resulting in precipitation, o(LA)n-PTX release was more gradual: t1/2 = 14 and 26 h for o(LA)8-PTX and o(LA)16-PTX, respectively. Notably, o(LA)8-PTX and o(LA)16-PTX in PEG-b-PLA micelles resisted backbiting chain end scission, based on reverse-phase HPLC analysis. By contrast, o(LA)8-PTX and o(LA)16-PTX degraded substantially in 1:1 acetonitrile:10 mM PBS, pH 7.4, at 37 degrees C, generating primarily o(LA)2-PTX. The IC50 value of o(LA)2-PTX was ~2.3 nM for A549 human lung cancer cells, equipotent with PTX in vitro. After weekly IV injections at 20 mg/kg as PEG-b-PLA micelles, o(LA)8-PTX induced tumor regression in A549 tumor-bearing mice, whereas PTX delayed tumor growth. Surprisingly, o(LA)8-PTX caused less toxicity than PTX in terms of change in body weight. In conclusion, o(LA)n acts as a novel promoiety, undergoing backbiting conversion without a reliance on metabolizing enzymes, and o(LA)n-PTX improves PTX delivery by PEG-b-PLA micelles, providing a strong justification for clinical evaluation. PMID- 27375001 TI - Management of the clinically N0 neck in squamous cell carcinoma of the maxillary alveolus and hard palate. AB - BACKGROUND: The purpose of this study was to evaluate active surveillance strategy in the clinically negative neck in maxillary squamous cell carcinoma (SCC). METHODS: One hundred fourteen consecutive patients diagnosed with oral maxillary SCC were analyzed retrospectively from 3 centers in The Netherlands. Analysis parameters included regional disease-free survival of N0 patients stratified for T classification, elective radiotherapy (RT) of the neck; and overall survival of the whole cohort, stratified by N classification; salvage neck surgery rates. RESULTS: Within the N0 cohort, 26.0% of the patients developed neck metastasis in the follow-up visits. Regional recurrence was not related to T classification or postoperative RT of the neck. Regional and locoregional recurrence were associated with diminished overall survival (p < .05). Regional metastasis was operable in 22 of 26 cases (85%). Only 1 patient presented with inoperable neck metastasis without local recurrence. CONCLUSION: Watchful waiting was feasible in this cohort. If meticulous follow-up is not available, elective neck dissection is recommended. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1794-1798, 2016. PMID- 27375002 TI - Liver Progenitors Isolated from Adult Healthy Mouse Liver Efficiently Differentiate to Functional Hepatocytes In Vitro and Repopulate Liver Tissue. AB - It has been proposed that tissue stem cells supply multiple epithelial cells in mature tissues and organs. However, it is unclear whether tissue stem cells generally contribute to cellular turnover in normal healthy organs. Here, we show that liver progenitors distinct from bipotent liver stem/progenitor cells (LPCs) persistently exist in mouse livers and potentially contribute to tissue maintenance. We found that, in addition to LPCs isolated as EpCAM+ cells, liver progenitors were enriched in CD45- TER119- CD31- EpCAM- ICAM-1+ fraction isolated from late-fetal and postnatal livers. ICAM-1+ liver progenitors were abundant by 4 weeks (4W) after birth. Although their number decreased with age, ICAM-1+ liver progenitors existed in livers beyond that stage. We established liver progenitor clones derived from ICAM-1+ cells between 1 and 20W and found that those clones efficiently differentiated into mature hepatocytes (MHs), which secreted albumin, eliminated ammonium ion, stored glycogen, and showed cytochrome P450 activity. Even after long-term culture, those clones kept potential to differentiate to MHs. When ICAM-1+ clones were transplanted into nude mice after retrorsine treatment and 70% partial hepatectomy, donor cells were incorporated into liver plates and expressed hepatocyte nuclear factor 4alpha, CCAAT/enhancer binding protein alpha, and carbamoylphosphate synthetase I. Moreover, after short-term treatment with oncostatin M, ICAM-1+ clones could efficiently repopulate the recipient liver tissues. Our results indicate that liver progenitors that can efficiently differentiate to MHs exist in normal adult livers. Those liver progenitors could be an important source of new MHs for tissue maintenance and repair in vivo, and for regenerative medicine ex vivo. Stem Cells 2016;34:2889 2901. PMID- 27375003 TI - Palladium-gold catalyst for the electrochemical reduction of CO2 to C1-C5 hydrocarbons. AB - Copper is a unique electrocatalyst for CO2 reduction, since it is one of the few catalysts able to produce methane, ethylene and ethane from CO2 with decent faradaic efficiencies. Here we report on the design and synthesis of a new non copper-containing catalyst able to reduce CO2 to C1 to C5 hydrocarbons. This catalyst was designed by combining a metal that binds CO strongly, Pd, with a metal that binds CO weakly, Au, in an attempt to tune the binding energy of CO. We show that a mixture of C1-C5 hydrocarbons and soluble products are produced from an onset potential of -0.8 VRHE. We propose that the higher hydrocarbons are formed via a polymerization of -CH2 groups adsorbed on the catalyst surface. PMID- 27375004 TI - Fetal sex is associated with maternal stimulated cytokine production, but not serum cytokine levels, in human pregnancy. AB - Some studies suggest that fetal sex plays a role in maternal physiological processes during pregnancy including glycemic control, blood pressure, and cortisol regulation. However, data examining fetal sex-specific differences in maternal immune parameters is lacking. In the current study, serum levels of interleukin(IL)-6, IL-8, and tumor necrosis factor(TNF)-alpha as well as LPS stimulated production of IL-6, IL-8, TNF-alpha, and IL-1beta by PBMCs incubated for 24h were assessed in early, mid, and late pregnancy among 80 women (46 with male and 34 with female fetuses). Linear mixed models showed that women carrying females versus males exhibited greater stimulated production of IL-6 at each timepoint (ps?0.03), TNF-alpha in early pregnancy (p=0.04), and IL-1beta in mid- and late pregnancy (ps?0.05). Despite changes in serum levels of IL-8 (p=0.002) and TNF-alpha (p<0.0001) across pregnancy, no differences in any serum cytokines were observed in relation to fetal sex (ps>0.85). In conclusion, in pregnant women, those carrying female versus male fetuses exhibited greater stimulated cytokine production across pregnancy. Differential inflammatory responses could affect maternal health and fetal development. Fetal sex should be considered as a factor in studies of maternal inflammation. These findings have relevance both clinically and conceptually. For example, maternal asthma is exacerbated among women carrying female versus male fetuses. In addition, data on associations between fetal sex and maternal immune function among women with health conditions (e.g., preeclampsia) and adverse pregnancy outcomes (e.g., preterm birth) would be informative. PMID- 27375005 TI - The involvement of prostaglandin E2 in interleukin-1beta evoked anorexia is strain dependent. AB - From experiments in mice in which the prostaglandin E2 (PGE2) synthesizing enzyme mPGES-1 was genetically deleted, as well as from experiments in which PGE2 was injected directly into the brain, PGE2 has been implicated as a mediator of inflammatory induced anorexia. Here we aimed at examining which PGE2 receptor (EP1-4) that was critical for the anorexic response to peripherally injected interleukin-1beta (IL-1beta). However, deletion of neither EP receptor in mice, either globally (for EP1, EP2, and EP3) or selectively in the nervous system (EP4), had any effect on the IL-1beta induced anorexia. Because these mice were all on a C57BL/6 background, whereas previous observations demonstrating a role for induced PGE2 in IL-1beta evoked anorexia had been carried out on mice on a DBA/1 background, we examined the anorexic response to IL-1beta in mice with deletion of mPGES-1 on a C57BL/6 background and a DBA/1 background, respectively. We confirmed previous findings that mPGES-1 knock-out mice on a DBA/1 background displayed attenuated anorexia to IL-1beta; however, mice on a C57BL/6 background showed the same profound anorexia as wild type mice when carrying deletion of mPGES-1, while displaying almost normal food intake after pretreatment with a cyclooxygenase-2 inhibitor. We conclude that the involvement of induced PGE2 in IL-1beta evoked anorexia is strain dependent and we suggest that different routes that probably involve distinct prostanoids exist by which inflammatory stimuli may evoke an anorexic response and that these routes may be of different importance in different strains of mice. PMID- 27375006 TI - Relation Between Erectile Dysfunction and Silent Myocardial Ischemia in Diabetic Patients: A Multidetector Computed Tomographic Coronary Angiographic Study. AB - INTRODUCTION: Erectile dysfunction (ED) can precede coronary artery disease. In addition, silent myocardial ischemia (SMI) is more common in diabetic patients and is a strong predictor of cardiac events and death. AIM: To evaluate the presence of SMI in patients with diabetes and ED using multidetector computed tomographic coronary angiography (MDCT-CA). METHODS: This study evaluated patients with diabetes and ED without any history of cardiac symptoms or signs. Erectile function was evaluated with the Sexual Health Inventory for Men score, erection hardness score (EHS), and maximal penile circumferential change by an erectometer. MDCT-CA was used for the detection of coronary artery stenosis. MAIN OUTCOME MEASURES: Sexual Health Inventory for Men score, EHS, maximal penile circumferential change, and coronary artery stenosis by MDCT-CA. RESULTS: Of 20 patients (mean age = 61.45 +/- 10.7 years), MDCT-CA showed coronary artery stenosis in 13 (65%) in the form of one-vessel disease (n = 6, 30%), two-vessel disease (n = 2, 10%), and three-vessel disease (n = 5, 25%). Fifty percent of patients showed at least 50% vessel lumen obstruction of the left anterior descending coronary artery, which was the most commonly affected vessel (55%). Fifteen percent (3 of 20) of patients had greater than 90% stenosis, and two of them underwent an immediate coronary angioplasty with stenting to prevent myocardial infarction. Maximum coronary artery stenosis was positively correlated with age (P = 0.016, r = 0.529) and negatively correlated with EHS (P = .046, r = -0.449). Multivariate regression analysis using age and EHS showed that age was the only independent predictor of SMI (P = .04). CONCLUSION: MDCT-CA can be a useful tool to identify SMI in diabetic patients with ED, especially in those of advanced age and/or with severe ED. PMID- 27375007 TI - Homozygosity for moyamoya disease risk allele leads to moyamoya disease with extracranial systemic and pulmonary vasculopathy. AB - Moyamoya disease is characterized by diffuse distal intracranial stenosis. Recently, RNF213 has been identified as a susceptibility gene in the development of this condition. Pulmonary hypertension is a rare progressive vasculopathy with an unknown etiology. The co-occurrence of pulmonary hypertension and Moyamoya disease has been described in four patients; however, whether this co-occurrence represents a chance association or a common vascular pathology has remained unknown. Here, we report two unrelated male patients who presented during their childhood with dyspnea on exertion. Systemic vascular imaging studies revealed the presence of pulmonary hypertension and Moyamoya disease in both patients. Medical exome sequencing revealed that both patients had a homozygous mutation for p.Arg4810Lys in RNF213. We suggest that homozygosity in RNF213 may lead to a novel entity involving the brain and lung. Interestingly, when present in a heterozygous state, this mutation causes a classic cerebral vascular disease, Moyamoya disease. In the homozygous state, the exact same mutation led to Moyamoya disease with extracranial systemic vasculopathy in at least two patients. From a clinical standpoint, cerebrovascular or pulmonary vascular investigations may be warranted in patients with pulmonary hypertension or Moyamoya disease, respectively. (c) 2016 Wiley Periodicals, Inc. PMID- 27375008 TI - Acute toxicity evaluation of a thiazolo arene ruthenium (II) complex in rats. AB - Recently, a series of thiazolo arene ruthenium complexes were found to be highly cytotoxic in vitro, on both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. The most active compound of the series, [(eta(6)-p cymene)Ru(L)Cl]Cl (L = 1-(2-(2-(3-chlorobenzylidene)hydrazinyl)-4-methylthiazol-5 yl)ethanone), was selected for an in vivo study in order to assess its safety profile. The ruthenium complex was administered to female Crl:WI rats orally, by gastric intubation and intraperitoneal injection. The hematological parameters and the histopathological changes in liver, kidneys, spleen and brain were investigated after a 14-days treatment. The substance was very well tolerated orally, with a LD50 value of over 2000 mg/kg body weight. Symptoms were observed only in the first day after intraperitoneal administration of the highest dose, with a LD50 value between 300 and 2000 mg/kg bw. The hematological profile was not modified at any of the tested doses, after both oral and intraperitoneal acute administration. Structural modifications (moderate lymphocytolysis) were identified only in the spleen at the highest tested dose. In conclusion, the thiazolo arene ruthenium complex was very well tolerated orally and had a low acute toxicity after intraperitoneal administration in Crl:WI rats The results justify further investigation to determine the in vivo therapeutic potential of this promising ruthenium complex. PMID- 27375010 TI - Clinical impact of GATA2 mutations in acute myeloid leukemia patients harboring CEBPA mutations: a study of the AML study group. PMID- 27375009 TI - Histone demethylase LSD1 controls the phenotypic plasticity of cancer cells. AB - Epigenetic mechanisms underlie the phenotypic plasticity of cells, while aberrant epigenetic regulation through genetic mutations and/or misregulated expression of epigenetic factors leads to aberrant cell fate determination, which provides a foundation for oncogenic transformation. Lysine-specific demethylase-1 (LSD1, KDM1A) removes methyl groups from methylated proteins, including histone H3, and is frequently overexpressed in various types of solid tumors and hematopoietic neoplasms. While LSD1 is involved in a wide variety of normal physiological processes, including stem cell maintenance and differentiation, it is also a key player in oncogenic processes, including compromised differentiation, enhanced cell motility and metabolic reprogramming. Here, we present an overview of how LSD1 epigenetically regulates cellular plasticity through distinct molecular mechanisms in different biological contexts. Targeted inhibition of the context dependent activities of LSD1 may provide a highly selective means to eliminate cancer cells. PMID- 27375011 TI - Surgical hip dislocation for removal of retained intra-articular bullets. AB - INTRODUCTION: Surgical hip dislocation with trochanteric osteotomy was introduced for the treatment of femoroacetabular impingement and other intra-articular pathologies of the hip. We expanded the indications to include removal of retained bullets in the hip joint as an alternative to hip arthroscopy. PATIENTS AND METHODS: We present a prospective case series of ten patients that were treated with a surgical hip dislocation for removal of retained bullets in the hip joint between January 2014 and October 2015 in a Level 1 trauma centre. The main outcome measurements were successful bullet removal, blood loss, surgical time and intraoperative complications. RESULTS: There were 8 males and 2 females with a mean age of mean age 27.3 years (range 20-32). All patients had one whole retained bullet for removal (right side: 8; left side: 2). In all cases the bullet could be removed in its entirety. The average surgical time was 73min (range 55-125) and the average blood loss 255ml (range 200-420). CONCLUSIONS: Surgical hip dislocation provides an unlimited view of the acetabulum and femoral head and neck and it therefore allows for easy removal of retained bullets. Osteocartilaginous lesions and concomitant fractures of the femoral head can be simultaneously evaluated and treated. PMID- 27375012 TI - Major incident triage: A consensus based definition of the essential life-saving interventions during the definitive care phase of a major incident. AB - INTRODUCTION: Triage is a key principle in the effective management of major incidents. The process currently relies on algorithms assigning patients to specific triage categories; there is, however, little guidance as to what these categories represent. Previously, these algorithms were validated against injury severity scores, but it is accepted now that the need for life-saving intervention is a more important outcome. However, the definition of a life saving intervention is unclear. The aim of this study was to define what constitutes a life-saving intervention, in order to facilitate the definition of an adult priority one patient during the definitive care phase of a major incident. METHODS: We conducted a modified Delphi study, using a panel of subject matter experts drawn from the United Kingdom and Republic of South Africa with a background in Emergency Care or Major Incident Management. The study was conducted using an online survey tool, over three rounds between July and December 2013. A four point Likert scale was used to seek consensus for 50 possible interventions, with a consensus level set at 70%. RESULTS: 24 participants completed all three rounds of the Delphi, with 32 life-saving interventions reaching consensus. CONCLUSIONS: This study provides a consensus definition of what constitutes a life-saving intervention in the context of an adult, priority one patient during the definitive care phase of a major incident. The definition will contribute to further research into major incident triage, specifically in terms of validation of an adult major incident triage tool. PMID- 27375013 TI - The effect of systemic injury score on the decision making of mangled lower extremities. AB - PURPOSE: Mangled lower extremity with Mangled extremity severity score (MESS) more than 7 are considered unsalvageable. We are looking for a factor helps us predicting the salvage potential in the patient with MESS score between 7 and 9. MATERIALS AND METHODS: We reviewed the patients with lower extremities open fracture type IIIB or IIIC and received salvaged procedure or amputation in CGMH between 2002/01 and 2010/09. The patients are subgroup according to their MESS score. ISS score, Gustilo open fracture classification were compared between patient with successful salvage and patient with delay amputation. Logistic regression and stepwise modeling were used to determine the effect of each covariate. RESULTS: 242 patients were enrolled in the study. 33 patients had primary amputation, 160 patients had successfully salvaged limbs and 49 patients received delay amputation. Among patients with MESS score less than 7, 116 patients had successful salvage limbs and 7 patients received delay amputation. Among patient with MESS between 7 and 9, 44 patients discharged with salvaged limbs and 39 patients were failed to salvage their limbs. Successful salvaged patients in this group had significant lower ISS score in compare to delay amputated patients. Patients with ISS score more than 18 in this group has higher delay amputated rate (P value=0.01). CONCLUSION: Systemic injury severity score can help us tell potentially salvaged patient from potentially amputated patient. In patients with MESS score between 7 and 9 concurrently have ISS score less then 17 are potentially salvageable. Level of Evidence & Study Type: Level 3 Retrospective cohort study/prognostic study. PMID- 27375015 TI - Endogenous GABAA receptor activity suppresses glioma growth. AB - Although genome alterations driving glioma by fueling cell malignancy have largely been resolved, less is known of the impact of tumor environment on disease progression. Here, we demonstrate functional GABAA receptor-activated currents in human glioblastoma cells and show the existence of a continuous GABA signaling within the tumor cell mass that significantly affects tumor growth and survival expectancy in mouse models. Endogenous GABA released by tumor cells, attenuates proliferation of the glioma cells with enriched expression of stem/progenitor markers and with competence to seed growth of new tumors. Our results suggest that GABA levels rapidly increase in tumors impeding further growth. Thus, shunting chloride ions by a maintained local GABAA receptor activity within glioma cells has a significant impact on tumor development by attenuating proliferation, reducing tumor growth and prolonging survival, a mechanism that may have important impact on therapy resistance and recurrence following tumor resection. PMID- 27375014 TI - Effect of the subcutaneous route for iliac screw insertion in lumbopelvic fixation for vertical unstable sacral fractures on the infection rate: A retrospective case series. AB - OBJECTIVE: To report the perioperative results and surgical outcomes of patients with vertical unstable sacral fractures who underwent lumbopelvic fixation through a modified subcutaneous route for iliac screw fixation. SUMMARY OF BACKGROUND DATA: Treating vertical unstable sacral fractures is still challenging for orthopedic surgeons. Among various methods for treating these fractures, lumbopelvic fixation provides a high reduction quality and promising stability for early weight-bearing ambulation. However, wound healing disturbance and surgical site infection (SSI) are the drawbacks of this extensive technique, especially after inserting iliac screws. METHODS: Here, we provide an alternative subcutaneous route for iliac screw insertion during lumbopelvic fixation surgery to lessen soft tissue retraction and injury, and thus decrease soft tissue complications. RESULTS: Using this modified technique, 28 patients with vertical unstable sacral fractures were treated between 2012 and 2014. One patient had an SSI (infection rate: 3.5%). All fractures were united with a mean sacral kyphosis correction angle of 10.5 degrees . The mean Majeed score of the 17 patients during the 12-month follow-up was 84.5. CONCLUSIONS: The subcutaneous route for iliac screw insertion is a simple, safe, and effective technique when performing lumbopelvic fixation for vertical unstable sacral fractures. PMID- 27375016 TI - Androgen deprivation leads to increased carbohydrate metabolism and hexokinase 2 mediated survival in Pten/Tp53-deficient prostate cancer. AB - Prostate cancer is characterized by a dependence upon androgen receptor (AR) signaling, and androgen deprivation therapy (ADT) is the accepted treatment for progressive prostate cancer. Although ADT is usually initially effective, acquired resistance termed castrate-resistant prostate cancer (CRPC) develops. PTEN and TP53 are two of the most commonly deleted or mutated genes in prostate cancer, the compound loss of which is enriched in CRPC. To interrogate the metabolic alterations associated with survival following ADT, we used an orthotopic model of Pten/Tp53 null prostate cancer. Metabolite profiles and associated regulators were compared in tumors from androgen-intact mice and in tumors surviving castration. AR inhibition led to changes in the levels of glycolysis and tricarboxylic acid (TCA) cycle pathway intermediates. As anticipated for inhibitory reciprocal feedback between AR and PI3K/AKT signaling pathways, pAKT levels were increased in androgen-deprived tumors. Elevated mitochondrial hexokinase 2 (HK2) levels and enzyme activities also were observed in androgen-deprived tumors, consistent with pAKT-dependent HK2 protein induction and mitochondrial association. Competitive inhibition of HK2-mitochondrial binding in prostate cancer cells led to decreased viability. These data argue for AKT-associated HK2-mediated metabolic reprogramming and mitochondrial association in PI3K-driven prostate cancer as one survival mechanism downstream of AR inhibition. PMID- 27375017 TI - EWS-FLI1-mediated suppression of the RAS-antagonist Sprouty 1 (SPRY1) confers aggressiveness to Ewing sarcoma. AB - Ewing sarcoma is characterized by chromosomal translocations fusing the EWS gene with various members of the ETS family of transcription factors, most commonly FLI1. EWS-FLI1 is an aberrant transcription factor driving Ewing sarcoma tumorigenesis by either transcriptionally inducing or repressing specific target genes. Herein, we showed that Sprouty 1 (SPRY1), which is a physiological negative feedback inhibitor downstream of fibroblast growth factor (FGF) receptors (FGFRs) and other RAS-activating receptors, is an EWS-FLI1 repressed gene. EWS-FLI1 knockdown specifically increased the expression of SPRY1, while other Sprouty family members remained unaffected. Analysis of SPRY1 expression in a panel of Ewing sarcoma cells showed that SPRY1 was not expressed in Ewing sarcoma cell lines, suggesting that it could act as a tumor suppressor gene in these cells. In agreement, induction of SPRY1 in three different Ewing sarcoma cell lines functionally impaired proliferation, clonogenic growth and migration. In addition, SPRY1 expression inhibited extracellular signal-related kinase/mitogen-activated protein kinase (MAPK) signaling induced by serum and basic FGF (bFGF). Moreover, treatment of Ewing sarcoma cells with the potent FGFR inhibitor PD-173074 reduced bFGF-induced proliferation, colony formation and in vivo tumor growth in a dose-dependent manner, thus mimicking SPRY1 activity in Ewing sarcoma cells. Although the expression of SPRY1 was low when compared with other tumors, SPRY1 was variably expressed in primary Ewing sarcoma tumors and higher expression levels were significantly associated with improved outcome in a large patient cohort. Taken together, our data indicate that EWS-FLI1-mediated repression of SPRY1 leads to unrestrained bFGF-induced cell proliferation, suggesting that targeting the FGFR/MAPK pathway can constitute a promising therapeutic approach for this devastating disease. PMID- 27375019 TI - PRIMA-1Met induces mitochondrial apoptosis through activation of caspase-2. PMID- 27375018 TI - A large-scale RNAi screen identifies LCMR1 as a critical regulator of Tspan8 mediated melanoma invasion. AB - Melanoma is the deadliest form of skin cancer owing to its proclivity to metastasise, and recently developed therapies have not yielded the expected results, because almost all patients relapse. Therefore, understanding the molecular mechanisms that underlie early invasion by melanoma cells is crucial to improving patient survival. We have previously shown that, whereas the Tetraspanin 8 protein (Tspan8) is undetectable in normal skin and benign lesions, its expression arises with the progression of melanoma and is sufficient to increase cell invasiveness. Therefore, to identify Tspan8 transcriptional regulators that could explain the onset of Tspan8 expression, thereby conferring an invasive phenotype, we performed an innovative RNA interference-based screen, which, for the first time, identified several Tspan8 repressors and activators, such as GSK3beta, PTEN, IQGAP1, TPT1 and LCMR1. LCMR1 is a recently identified protein that is overexpressed in numerous carcinomas; its expression and role, however, had not previously been studied in melanoma. The present study identified Tspan8 as the first LCMR1 target that could explain its function in carcinogenesis. LCMR1 modulation was sufficient to positively regulate endogenous Tspan8 expression, with concomitant in vitro phenotypic changes such as loss of melanoma cell-matrix adherence and increase in invasion, and Tspan8 expression promoted tumourigenicity in vivo. Moreover, LCMR1 and Tspan8 overexpression were shown to correlate in melanoma lesions, and both proteins could be downregulated in vitro by vemurafenib. In conclusion, this study highlights the importance of Tspan8 and its regulators in the control of early melanoma invasion and suggests that they may be promising new therapeutic targets downstream of the RAF-MEK-ERK signalling pathway. PMID- 27375021 TI - Cadherin-6 promotes EMT and cancer metastasis by restraining autophagy. AB - The transdifferentiation of epithelial cells toward a mesenchymal condition (EMT) is a complex process that allows tumor cells to migrate to ectopic sites. Cadherins are not just structural proteins, but they act as sensors of the surrounding microenvironment and as signaling centers for cellular pathways. However, the molecular mechanisms underlying these signaling functions remain poorly characterized. Cadherin-6 (CDH6) is a type 2 cadherin, which drives EMT during embryonic development and it is aberrantly re-activated in cancer. We recently showed that CDH6 is a TGFbeta target and an EMT marker in thyroid cancer, suggesting a role for this protein in the progression of this type of tumor. Papillary thyroid carcinomas (PTCs) are usually indolent lesions. However, metastatic spreading occurs in about 5% of the cases. The identification of molecular markers that could early predict the metastatic potential of these lesions would be strategic to design more tailored approaches and reduce patients overtreatment. In this work, we assessed the role of CDH6 in the metastatic progression of thyroid cancer. We showed that loss of CDH6 expression profoundly changes cellular architecture, alters the inter-cellular interaction modalities and attenuates EMT features in thyroid cancer cells. Using a yeast two-hybrid screening approach, based on a thyroid cancer patients library, we showed that CDH6 directly interacts with GABARAP, BNIP3 and BNIP3L, and that through these interactions CDH6 restrains autophagy and promotes re-organization of mitochondrial network through a DRP1-mediated mechanism. Analysis of the LIR domains suggests that the interaction with the autophagic machinery may be a common feature of many cadherin family members. Finally, the analysis of CDH6 expression in a unique cohort of human PTCs showed that CDH6 expression marks specifically EMT cells. and it is strongly associated with metastatic behavior and worse outcome of PTCs. PMID- 27375020 TI - Interleukin-17 promotes prostate cancer via MMP7-induced epithelial-to mesenchymal transition. AB - Chronic inflammation has been associated with a variety of human cancers including prostate cancer. Interleukin-17 (IL-17) is a critical pro-inflammatory cytokine, which has been demonstrated to promote development of prostate cancer, colon cancer, skin cancer, breast cancer, lung cancer and pancreas cancer. IL-17 promotes prostate adenocarcinoma with a concurrent increase of matrix metalloproteinase 7 (MMP7) expression in mouse prostate. Whether MMP7 mediates IL 17's action and the underlying mechanisms remain unknown. We generated Mmp7 and Pten double knockout (KO) (Mmp7-/-) mouse model and demonstrated that MMP7 promotes prostate adenocarcinoma through induction of epithelial-to-mesenchymal transition (EMT) in Pten-null mice. MMP7 disrupted E-cadherin/beta-catenin complex to upregulate EMT transcription factors in mouse prostate tumors. IL-17 receptor C and Pten double KO mice recapitulated the weak EMT characteristics observed in Mmp7-/- mice. IL-17 induced MMP7 and EMT in human prostate cancer LNCaP, C4-2B and PC-3 cell lines, while small interfering RNA knockdown of MMP7 inhibited IL-17-induced EMT. Compound III, a selective MMP7 inhibitor, decreased development of invasive prostate cancer in Pten single KO mice. In human normal prostates and prostate tumors, IL-17 mRNA levels were positively correlated with MMP7 mRNA levels. These findings demonstrate that MMP7 mediates IL-17's function in promoting prostate carcinogenesis through induction of EMT, indicating IL-17 MMP7-EMT axis as a potential target for developing new strategies in the prevention and treatment of prostate cancer. PMID- 27375024 TI - STIM1, a direct target of microRNA-185, promotes tumor metastasis and is associated with poor prognosis in colorectal cancer. PMID- 27375023 TI - TNFalpha-activated mesenchymal stromal cells promote breast cancer metastasis by recruiting CXCR2+ neutrophils. AB - Mesenchymal stromal cells (MSCs) tend to infiltrate into tumors and form a major component of the tumor microenvironment. Our previous work demonstrated that tumor necrosis factor alpha (TNFalpha)-activated MSCs significantly promoted tumor growth. However, the role of TNFalpha-treated MSCs in tumor metastasis remains elusive. Employing a lung metastasis model of murine breast cancer, we found that TNFalpha-activated MSCs strikingly enhanced tumor metastasis compared with normal MSCs. We analyzed the chemokine profiles and found that the expression of CCL5, CCR2 and CXCR2 ligands were enhanced in TNFalpha-activated MSCs. Using genetic or pharmacological strategies to inhibit CCL5 or CCR2, we demonstrated that CCL5 and CCR2 ligands were indispensable in supporting TNFalpha activated MSCs to promote tumor metastasis. Analysis of immune cells revealed that CXCR2 ligands (CXCL1, CXCL 2 and CXCL5) expressed by TNFalpha-activated MSCs efficiently recruited CXCR2+ neutrophils into tumor. These neutrophils were responsible for the pro-metastatic effect of MSCs since inhibition of this chemotaxis abolished increased neutrophil recruitment and tumor metastasis. The interaction between neutrophils and tumor cells resulted in markedly elevated metastasis-related genes by tumor cells, including CXCR4, CXCR7, MMP12, MMP13, IL 6 and TGFbeta. Importantly, in IL8high human breast cancer samples, we also observed similar alterations of gene expression. Collectively, our findings demonstrate that TNFalpha-activated MSCs promote tumor metastasis via CXCR2+ neutrophil recruitment. PMID- 27375022 TI - Neuroendocrine prostate cancer (NEPCa) increased the neighboring PCa chemoresistance via altering the PTHrP/p38/Hsp27/androgen receptor (AR)/p21 signals. AB - Prostatic neuroendocrine cells (NE) are an integral part of prostate cancer (PCa) and are associated with PCa progression. As the current androgen deprivation therapy with anti-androgens may promote the neuroendocrine PCa (NEPCa) development, and few therapies can effectively suppress NEPCa, understanding the impact of NEPCa on PCa progression may help us to develop better therapies to battle PCa. Here, we found NEPCa cells could increase the docetaxel resistance of their neighboring PCa cells. Mechanism dissection revealed that through secretion of PTHrP, NEPCa cells could alter the p38/MAPK/Hsp27 signals in their neighboring PCa cells that resulted in increased androgen receptor (AR) activity via promoting AR nuclear translocation. The consequences of increased AR function might then increase docetaxel resistance via increasing p21 expression. In vivo xenograft mice experiments also confirmed that NEPCa could increase the docetaxel resistance of neighboring PCa, and targeting this newly identified PTHrP/p38/Hsp27/AR/p21 signaling pathway with either p38 inhibitor (SB203580) or shPTHrP may result in improving/restoring the docetaxel sensitivity to better suppress PCa. PMID- 27375025 TI - PERK inhibits DNA replication during the Unfolded Protein Response via Claspin and Chk1. AB - Stresses such as hypoxia, nutrient deprivation and acidification disturb protein folding in the endoplasmic reticulum (ER) and activate the Unfolded Protein Response (UPR) to trigger adaptive responses through the effectors, PERK, IRE1 and ATF6. Most of these responses relate to ER homoeostasis; however, here we show that the PERK branch of the UPR also controls DNA replication. Treatment of cells with the non-genotoxic UPR agonist thapsigargin led to a rapid inhibition of DNA synthesis that was attributable to a combination of DNA replication fork slowing and reduced replication origin firing. DNA synthesis inhibition was dependent on the UPR effector PERK and was associated with phosphorylation of the checkpoint adaptor protein Claspin and activation of the Chk1 effector kinase, both of which occurred in the absence of detectable DNA damage. Remarkably, thapsigargin did not inhibit bulk DNA synthesis or activate Chk1 in cells depleted of Claspin, or when Chk1 was depleted or subject to chemical inhibition. In each case thapsigargin-resistant DNA synthesis was due to an increase in replication origin firing that compensated for reduced fork progression. Taken together, our results unveil a new aspect of PERK function and previously unknown roles for Claspin and Chk1 as negative regulators of DNA replication in the absence of genotoxic stress. Because tumour cells proliferate in suboptimal environments, and frequently show evidence of UPR activation, this pathway could modulate the response to DNA replication-targeted chemotherapies. PMID- 27375026 TI - Carboxypeptidase E (CPE) inhibits the secretion and activity of Wnt3a. AB - The Wnt pathway has essential roles in cell proliferation, cell fate determination and tumorigenesis by regulating the expression of a wide range of target genes. As a core signaling cascade, the canonical Wnt pathway is regulated at different levels by numerous proteins. We have previously shown that carboxypeptidase E (CPE) is a novel regulator of the canonical Wnt signaling pathway. Here, we show that CPE and the Wnt3a ligand are co-secreted from cells. We show that although the C'-terminal Lys residue of Wnt3a is critical for its activity and is important for the effect of CPE on the Wnt pathway, CPE does not execute its effect by removing this Wnt3a residue. Interestingly, CPE through its N'-terminal sequence, forms aggregates with Wnt3a and possible endoplasmic reticulum (ER) stress leading to its loss of function. Together, our current results provide a mechanistic insight into the way CPE regulates the canonical Wnt signaling pathway. PMID- 27375027 TI - p53 binds the mdmx mRNA and controls its translation. AB - MDMX and MDM2 are two nonredundant essential regulators of p53 tumor suppressor activity. MDM2 controls p53 expression levels, whereas MDMX is predominantly a negative regulator of p53 trans-activity. The feedback loops between MDM2 and p53 are well studied and involve both negative and positive regulation on transcriptional, translational and post-translational levels but little is known on the regulatory pathways between p53 and MDMX. Here we show that overexpression of p53 suppresses mdmx mRNA translation in vitro and in cell-based assays. The core domain of p53 binds the 5' untranslated region (UTR) of the mdmx mRNA in a zinc-dependent manner that together with a trans-suppression domain located in p53 N-terminus controls MDMX synthesis. This interaction can be visualized in the nuclear and cytoplasmic compartment. Fusion of the mdmx 5'UTR to the ovalbumin open reading frame leads to suppression of ovalbumin synthesis. Interestingly, the transcription inactive p53 mutant R273H has a different RNA-binding profile compared with the wild-type p53 and differentiates the synthesis of MDMX isoforms. This study describes p53 as a trans-suppressor of the mdmx mRNA and adds a further level to the intricate feedback system that exist between p53 and its key regulatory factors and emphasizes the important role of mRNA translation control in regulating protein expression in the p53 pathway. PMID- 27375028 TI - Keratin-associated protein 5-5 controls cytoskeletal function and cancer cell vascular invasion. AB - Cancer cell vascular invasion is a crucial step in the malignant progression toward metastasis. Here we used a genome-wide RNA interference screen with E0771 mammary cancer cells to uncover drivers of endothelial monolayer invasion. We identified keratin-associated protein 5-5 (Krtap5-5) as a candidate. Krtap5-5 belongs to a large protein family that is implicated in crosslinking keratin intermediate filaments during hair formation, yet these Krtaps have no reported role in cancer. Depletion of Krtap5-5 from cancer cells led to cell blebbing and a loss of keratins 14 and 18, in addition to the upregulation of vimentin intermediate filaments. This intermediate filament subtype switching induced dysregulation of the actin cytoskeleton and reduced the expression of hemidesmosomal alpha6/beta4-integrins. We further demonstrate that knockdown of keratin 18 phenocopies the loss of Krtap5-5, suggesting that Krtap5-5 crosstalks with keratin 18 in E0771 cells. Disruption of the keratin cytoskeleton by perturbing Krtap5-5 function broadly altered the expression of cytoskeleton regulators and the localization of cell surface markers. Krtap5-5 depletion did not impact cell viability but reduced cell motility and extracellular matrix invasion, as well as extravasation of cancer cells into tissues in zebrafish and mice. We conclude that Krtap5-5 is a previously unknown regulator of cytoskeletal function in cancer cells that modulates motility and vascular invasion. Thus, in addition to its physiologic function, a Krtap can serve as a switch toward malignant progression. PMID- 27375029 TI - Possible origin of B chromosome in Dichotomius sericeus (Coleoptera). AB - B chromosomes have so far been described in about 80 species of Coleoptera, mainly using conventional staining analysis. In this study, 152 individuals of the dung beetle Dichotomius sericeus (Coleoptera), collected from three isolated geographical areas in the State of Pernambuco, Brazil, were analyzed to determine the frequency, prevalence, distribution, meiotic behavior, and possible B chromosome origin. The cytogenetic analysis consisted of conventional staining, C banding, triple fluorochrome staining (CMA3/DA/DAPI), and fluorescent in situ hybridization using ribosomal DNAs (rDNAs) and H3 histone gene as probes, as well as microdissection and chromosome painting of the B chromosome. The B chromosomes were detected in all populations analyzed. Analysis revealed the heterochromatic nature and the presence of G+C-rich blocks and 18S rDNA on the B chromosome. FISH with DNA from microdissected B chromosome painted the entire extension of the B chromosome for all populations, besides the pericentromeric regions of all the autosomes, as well as the X chromosome. Finally, cross-hybridization in nine related species of Dichotomius using the microdissected B chromosome as probe did not reveal any hybridization signal. The results suggest an intraspecific and monophyletic origin for B chromosomes in D. sericeus, probably from the second or third autosomal pair. PMID- 27375030 TI - Changes in threat-related cognitions and experiential avoidance in group-based transdiagnostic CBT for anxiety disorders. AB - Group-based Transdiagnostic Cognitive Behavioral Therapy (TCBT) for anxiety disorders aims to target common factors to produce beneficial effects on multiple anxiety disorders at once. While there is growing evidence that various anxiety disorders can be effectively treated by this approach, the common factors contributing to these treatment effects are not well delineated. In a sample of 48 Veterans who completed Group-based TCBT, the current study examined change in threat perception and change in experiential avoidance pre to post-treatment and as potential mediators of changes in negative affect and personalized fear ratings. Results indicated that both threat perception and experiential avoidance were significantly reduced during treatment. Additionally, reductions in both threat perception and experiential avoidance significantly predicted reductions in negative affect and fear ratings. When change in threat perception and change in experiential avoidance were examined simultaneously, both remained significant predictors of changes in negative affect though only experiential avoidance predicted changes in fear ratings. Thus, both reductions in threat perception and experiential avoidance may mediate the broad treatment effects observed in group based TCBT. Directions for future research are discussed. PMID- 27375031 TI - Nanoscale Charge Percolation Analysis in Polymer-Sorted (7,5) Single-Walled Carbon Nanotube Networks. AB - The current percolation in polymer-sorted semiconducting (7,5) single-walled carbon nanotube (SWNT) networks, processed from solution, is investigated using a combination of electrical field-effect measurements, atomic force microscopy (AFM), and conductive AFM (C-AFM) techniques. From AFM measurements, the nanotube length in the as-processed (7,5) SWNTs network is found to range from ~100 to ~1500 nm, with a SWNT surface density well above the percolation threshold and a maximum surface coverage ~58%. Analysis of the field-effect charge transport measurements in the SWNT network using a 2D homogeneous random-network stick percolation model yields an exponent coefficient for the transistors OFF currents of 16.3. This value is indicative of an almost ideal random network containing only a small concentration of metallic SWNTs. Complementary C-AFM measurements on the other hand enable visualization of current percolation pathways in the xy plane and reveal the isotropic nature of the as-spun (7,5) SWNT networks. This work demonstrates the tremendous potential of combining advanced scanning probe techniques with field-effect charge transport measurements for quantification of key network parameters including current percolation, metallic nanotubes content, surface coverage, and degree of SWNT alignment. Most importantly, the proposed approach is general and applicable to other nanoscale networks, including metallic nanowires as well as hybrid nanocomposites. PMID- 27375032 TI - The Genetics of Drug Hypersensitivity Reactions. AB - DHRs are induced by various mechanisms and encompass a heterogeneous set of potentially life-threatening clinical entities. In addition to environmental effects, individual factors play a key role in this intricate puzzle. However, despite commendable efforts in recent years to identify individual predisposing factors, our knowledge of the genetic basis of these reactions remains incomplete. In this manuscript, we summarize current research on the genetics of DHRs, focusing on specific immune-mediated reactions (immediate and nonimmediate) and on pharmacologically mediated reactions (cross-intolerance to nonsteroidal anti-inflammatory drugs). We also provide some thoughts on potential technological approaches that would help us to decipher the molecular mechanisms underlying DHRs. We believe this manuscript will be of interest not only for allergists and basic researchers in the field, but also for clinicians from various areas of expertise who manage these reactions in their clinical practice. PMID- 27375033 TI - Updated 2016 EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer. AB - CONTEXT: Invasive bladder cancer is a frequently occurring disease with a high mortality rate despite optimal treatment. The European Association of Urology (EAU) Muscle-invasive and Metastatic Bladder Cancer (MIBC) Guidelines are updated yearly and provides information to optimise diagnosis, treatment, and follow-up of this patient population. OBJECTIVE: To provide a summary of the EAU guidelines for physicians and patients confronted with muscle-invasive and metastatic bladder cancer. EVIDENCE ACQUISITION: An international multidisciplinary panel of bladder cancer experts reviewed and discussed the results of a comprehensive literature search of several databases covering all sections of the guidelines. The panel defined levels of evidence and grades of recommendation according to an established classification system. EVIDENCE SYNTHESIS: Epidemiology and aetiology of bladder cancer are discussed. The proper diagnostic pathway, including demands for pathology and imaging, is outlined. Several treatment options, including bladder-sparing treatments and combinations of treatment modalities (different forms of surgery, radiation therapy, and chemotherapy) are described. Sequencing of these modalities is discussed. Potential indications and contraindications, such as comorbidity, are related to treatment choice. There is a new paragraph on organ-sparing approaches, both in men and in women, and on minimal invasive surgery. Recommendations for chemotherapy in fit and unfit patients are provided including second-line options. Finally, a follow-up schedule is provided. CONCLUSIONS: The current summary of the EAU Muscle-invasive and Metastatic Bladder Cancer Guidelines provides an up-to-date overview of the available literature and evidence dealing with diagnosis, treatment, and follow-up of patients with metastatic and muscle-invasive bladder cancer. PATIENT SUMMARY: Bladder cancer is an important disease with a high mortality rate. These updated guidelines help clinicians refine the diagnosis and select the appropriate therapy and follow-up for patients with metastatic and muscle-invasive bladder cancer. PMID- 27375034 TI - Re: Effects of Testosterone Treatment in Older Men. PMID- 27375035 TI - Highly sensitive myosin phosphorylation analysis in the renal afferent arteriole. AB - The regulation of smooth muscle contraction and relaxation involves phosphorylation and dephosphorylation of regulatory proteins, particularly myosin. To elucidate the regulatory mechanisms, analyzing the phosphorylation signal transduction is crucial. Although a pharmacological approach with selective inhibitors is sensitive and a useful technique, it leads to speculation regarding a signaling pathway but does not provide direct evidence of changes at a molecular level. We developed a highly sensitive biochemical technique to analyze phosphorylation by adapting Phos-tag SDS-PAGE. With this technique, we successfully analyzed myosin light chain (LC20) phosphorylation in tiny renal afferent arterioles. In the rat afferent arterioles, endothelin-1 (ET-1) induced diphosphorylation of LC20 at Ser19 and Thr18 as well as monophosphorylation at Ser19 via ET B receptor activation. Considering that LC20 diphosphorylation can decrease the rate of dephosphorylation and thus relaxation, we concluded that LC20 diphosphorylation contributes, at least in part, to the prolonged contraction induced by ET-1 in the renal afferent arteriole. PMID- 27375036 TI - Countrywide dissemination of a DHA-1-type plasmid-mediated AmpC beta-lactamase producing Klebsiella pneumoniae ST11 international high-risk clone in Hungary, 2009-2013. AB - The first plasmid-mediated AmpC beta-lactamase-producing Klebsiella pneumoniae (pAmpC KP) isolate was detected in December 2009 in Hungary. Hungarian microbiological laboratories were asked to send all KP strains showing cefoxitin resistance and decreased susceptibility or resistance to any third-generation cephalosporins to the Reference Laboratories at the National Center for Epidemiology. Investigation was conducted in order to outline spatio-temporal distribution and genetic characterization of pAmpC-KP isolates in Hungary. Between December 2009 and December 2013, 312 consecutive KP clinical isolates were confirmed as producing pAmpCs. All isolates showed resistance to third generation cephalosporins, aminoglycosides and fluoroquinolones, and 77 % were non-susceptible to at least one carbapenem. Analysis of beta-lactamase genes showed blaDHA-1 in all and additionally blaCTX-M-15 in 90 % of isolates. PFGE typing revealed 12 pulsotypes; of these, KP053 (262/312) and KP070 (38/312) belonged to sequence type ST11 and comprised 96 % of the isolates. The blaDHA-1 and blaCTX-M-15 co-producing KP053/ST11 clone affected 234 patients and spread to 55 healthcare centres across Hungary during the study period. Three KP053 isolates were also resistant to colistin. In two of these, the mgrB gene was truncated by IS10R, while in the third isolate, insertional inactivation of mgrB by ISKPn14 was identified. Hungary is the first European country showing endemic spread of blaDHA-1 facilitated by the international high-risk clone ST11. The rapid countrywide spread of this multidrug-resistant clone seriously endangers Hungarian healthcare facilities and warrants strengthening of infection control practices and prudent use of carbapenems and colistin. PMID- 27375037 TI - Mesophase structure and behaviour in bulk and restricted geometry of a dimeric compound exhibiting a nematic-nematic transition. AB - We present structural studies of a dimeric compound composed of a central heptyl spacer linking two mesogens consisting of terphenyl units at which two adjacent fluoro groups are attached to each central ring. The terminal rings are linked to pentyl chains as terminal groups. The material exhibits a nematic-nematic transition and a low temperature modulated phase. The higher temperature nematic phase was found to exhibit an anomaly of the bend elastic constant similar to that of the dimers with N-Ntb phase sequence, and the physical properties of the low-temperature nematic phase are similar to those of the known Ntb materials. The structure of the low-temperature modulated smectic/columnar phase is described together with its ability to form freely suspended films and fibres. The relation of the modulated structure to the fibre formation and to the appearance of the labyrinthine instability in freely-suspended films is discussed. PMID- 27375038 TI - Deep vein thrombosis and pulmonary embolism. AB - Deep vein thrombosis and pulmonary embolism, collectively referred to as venous thromboembolism, constitute a major global burden of disease. The diagnostic work up of suspected deep vein thrombosis or pulmonary embolism includes the sequential application of a clinical decision rule and D-dimer testing. Imaging and anticoagulation can be safely withheld in patients who are unlikely to have venous thromboembolism and have a normal D-dimer. All other patients should undergo ultrasonography in case of suspected deep vein thrombosis and CT in case of suspected pulmonary embolism. Direct oral anticoagulants are first-line treatment options for venous thromboembolism because they are associated with a lower risk of bleeding than vitamin K antagonists and are easier to use. Use of thrombolysis should be limited to pulmonary embolism associated with haemodynamic instability. Anticoagulant treatment should be continued for at least 3 months to prevent early recurrences. When venous thromboembolism is unprovoked or secondary to persistent risk factors, extended treatment beyond this period should be considered when the risk of recurrence outweighs the risk of major bleeding. PMID- 27375039 TI - Benefits of gene therapy for both eyes. PMID- 27375041 TI - miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4. AB - Breast cancer is a leading cause of cancer-related mortality among women. Altered fucosylation was found to be closely associated with tumorigenesis and metastasis of breast cancer. MicroRNAs (miRNAs) are important regulators of cell proliferation and metastasis, and aberrant miRNA expression has been observed in breast cancer. The present study aimed to evaluate the level of fucosyltransferase IV (FUT4) and miR-493-5p in breast cancer and investigate their relationship. In the present study, we demonstrated the differential expressional profiles of FUT4 and miR-493-5p in 29 clinical breast cancer tissues, matched adjacent tissue samples and two breast carcinoma cell lines (MCF 7 and MDA-MB-231). Briefly, altered expression levels of FUT4 modified the invasive activities and tumorigenicity of the MCF-7 and MDA-MB-231 cells. Further study demonstrated that miR-493-5p plays a role as a suppressor in breast cancer cell invasion and tumorigenicity. Moreover, the expression levels of miR-493-5p were inversely proportional to those of FUT4 both at the mRNA and protein levels. Luciferase reporter assays confirmed that miR-493-5p bound to the 3'-untranslated (3'-UTR) region of FUT4, and inhibited the expression of FUT4 in breast cancer cells. Taken together, our data suggest that FUT4 may have a potential role in the treatment of breast cancer, as well as miR-493-5p is a novel regulator of invasiveness and tumorigenicity of breast cancer cells through targeting FUT4. The miR-493-5p/FUT4 pathway has therapeutic potential in breast cancer. PMID- 27375042 TI - Elucidation of transport mechanism and enhanced alkali ion transference numbers in mixed alkali metal-organic ionic molten salts. AB - Mixed salts of Ionic Liquids (ILs) and alkali metal salts, developed as electrolytes for lithium and sodium batteries, have shown a remarkable ability to facilitate high rate capability for lithium and sodium electrochemical cycling. It has been suggested that this may be due to a high alkali metal ion transference number at concentrations approaching 50 mol% Li(+) or Na(+), relative to lower concentrations. Computational investigations for two IL systems illustrate the formation of extended alkali-anion aggregates as the alkali metal ion concentration increases. This tends to favor the diffusion of alkali metal ions compared with other ionic species in electrolyte solutions; behavior that has recently been reported for Li(+) in a phosphonium ionic liquid, thus an increasing alkali transference number. The mechanism of alkali metal ion diffusion via this extended coordination environment present at high concentrations is explained and compared to the dynamics at lower concentrations. Heterogeneous alkali metal ion dynamics are also evident and, somewhat counter intuitively, it appears that the faster ions are those that are generally found clustered with the anions. Furthermore these fast alkali metal ions appear to correlate with fastest ionic liquid solvent ions. PMID- 27375040 TI - Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial. AB - BACKGROUND: Safety and efficacy have been shown in a phase 1 dose-escalation study involving a unilateral subretinal injection of a recombinant adeno associated virus (AAV) vector containing the RPE65 gene (AAV2-hRPE65v2) in individuals with inherited retinal dystrophy caused by RPE65 mutations. This finding, along with the bilateral nature of the disease and intended use in treatment, prompted us to determine the safety of administration of AAV2-hRPE65v2 to the contralateral eye in patients enrolled in the phase 1 study. METHODS: In this follow-on phase 1 trial, one dose of AAV2-hRPE65v2 (1.5 * 10(11) vector genomes) in a total volume of 300 MUL was subretinally injected into the contralateral, previously uninjected, eyes of 11 children and adults (aged 11-46 years at second administration) with inherited retinal dystrophy caused by RPE65 mutations, 1.71-4.58 years after the initial subretinal injection. We assessed safety, immune response, retinal and visual function, functional vision, and activation of the visual cortex from baseline until 3 year follow-up, with observations ongoing. This study is registered with ClinicalTrials.gov, number NCT01208389. FINDINGS: No adverse events related to the AAV were reported, and those related to the procedure were mostly mild (dellen formation in three patients and cataracts in two). One patient developed bacterial endophthalmitis and was excluded from analyses. We noted improvements in efficacy outcomes in most patients without significant immunogenicity. Compared with baseline, pooled analysis of ten participants showed improvements in mean mobility and full-field light sensitivity in the injected eye by day 30 that persisted to year 3 (mobility p=0.0003, white light full-field sensitivity p<0.0001), but no significant change was seen in the previously injected eyes over the same time period (mobility p=0.7398, white light full-field sensitivity p=0.6709). Changes in visual acuity from baseline to year 3 were not significant in pooled analysis in the second eyes or the previously injected eyes (p>0.49 for all time-points compared with baseline). INTERPRETATION: To our knowledge, AAV2-hRPE65v2 is the first successful gene therapy administered to the contralateral eye. The results highlight the use of several outcome measures and help to delineate the variables that contribute to maximal benefit from gene augmentation therapy in this disease. FUNDING: Center for Cellular and Molecular Therapeutics at The Children's Hospital of Philadelphia, Spark Therapeutics, US National Institutes of Health, Foundation Fighting Blindness, Institute for Translational Medicine and Therapeutics, Research to Prevent Blindness, Center for Advanced Retinal and Ocular Therapeutics, Mackall Foundation Trust, F M Kirby Foundation, and The Research Foundation-Flanders. PMID- 27375043 TI - Commentary on Cavazos-Rehg and Colleagues: Selected State Policies and Associations with Alcohol Use Behaviors and Risky Driving Behaviors Among Youth Findings from the Monitoring the Future Study. PMID- 27375046 TI - Autonomic dysfunction in chronic kidney disease: An old problem in a new era. PMID- 27375044 TI - High resting metabolic rate among Amazonian forager-horticulturalists experiencing high pathogen burden. AB - OBJECTIVES: Resting metabolic rate (RMR) reflects energetic costs of homeostasis and accounts for 60 to 75% of total energy expenditure (TEE). Lean mass and physical activity account for much RMR variability, but the impact of prolonged immune activation from infection on human RMR is unclear in naturalistic settings. We evaluate the effects of infection on mass-corrected RMR among Bolivian forager-horticulturalists, and assess whether RMR declines more slowly with age than in hygienic sedentary populations, as might be expected if older adults experience high pathogen burden. MATERIALS AND METHODS: RMR was measured by indirect calorimetry (Fitmate MED, Cosmed) in 1,300 adults aged 20 to 90 and TEE was measured using doubly labeled water (n = 40). Immune biomarkers, clinical diagnoses, and anthropometrics were collected by the Tsimane Health and Life History Project. RESULTS: Tsimane have higher RMR and TEE than people in sedentary industrialized populations. Tsimane RMR is 18 to 47% (women) and 22 to 40% (men) higher than expected using six standard prediction equations. Tsimane mass-corrected TEE is similarly elevated compared to Westerners. Elevated leukocytes and helminths are associated with excess RMR in multivariate regressions, and jointly result in a predicted excess RMR of 10 to 15%. After age 40, RMR declines by 69 kcal/decade (p < .0001). Controlling for lean mass and height accounts for 71% of age-related RMR decline, and adding indicators of infection minimally affects the age slope. The residual level of age-related decline from age 40 is 1.2% per decade. CONCLUSION: High pathogen burden may lead to higher metabolic costs, which may be offset by smaller body mass or other energy-sparing mechanisms. PMID- 27375045 TI - Sex differences in the effects of social defeat on brain and behavior in the California mouse: Insights from a monogamous rodent. AB - Women are nearly twice as likely as men to be diagnosed with major depressive disorder, yet the use of female animal models in studying the biological basis of depression lags behind that of males. The social defeat model uses social stress to generate depression-like symptoms in order to study the neurobiological mechanisms. In general, social defeat is difficult to apply in female rodents. However, male and female California mice (Peromyscus californicus) are territorial. This allows defeat to be studied in both sexes. Males exposed to defeat tend to exhibit proactive coping mechanisms and demonstrate aggression and reduced cognitive flexibility. Females exposed to defeat engage more in reactive coping mechanisms which is highlighted by social avoidance and low aggression. Importantly, effects of defeat on social interaction behavior in females is independent of adult gonadal steroids. These behavioral phenotypes are associated with sex-specific changes in arginine vasopressin (AVP) and oxytocin (OT), closely related peptides that regulate social behavior and stress reactivity. In brain regions associated with stress responses and social behavior, defeat induced long term decreases in AVP activity and increases in OT activity in males and females respectively. Intranasal OT administration was shown to mimic the effects of defeat-induced increases in endogenous OT activity, causing social withdrawal in undefeated females. This suggests that inhibition of OT activity could reduce the impact of stress on behavior in females. These results highlight the value of maintaining diverse rodent models in the search for sex-specific pharmacological approaches to treating mood disorders. PMID- 27375047 TI - Cyclic fatigue behavior of nickel-titanium dental rotary files in clinical simulated root canals. AB - BACKGROUND/PURPOSE: Dental rotary instruments can be applied in multiple conditions of canals, but unpredictable fatigue fracture may happen. This study evaluated the fatigue lives of two batches of nickel-titanium (NiTi) dental rotary files operating in clinically simulated root canals. METHODS: Single-step cyclic fatigue tests were carried out to assess the performance of two batches of NiTi files (ProTaper and ProFile) in nine combinations of simulated canals (cylinder radii 5 mm, 7.5 mm, and 10 mm, and insertion angles 20 degrees , 40 degrees , and 60 degrees ). Two-step cyclic fatigue tests were carried out in simulated root canals with the same radius by using the following two sets of insertion angles: (20 degrees , 40 degrees ), (20 degrees , 60 degrees ), (40 degrees , 20 degrees ), and (60 degrees , 20 degrees ). Fracture surfaces were observed by scanning electron microscopy. RESULTS: The single-step cyclic fatigue results showed that cyclic fatigue lives of the files decreased with increasing insertion angles or decreasing cylinder radius. The ProFile #25 .04 file was more fatigue resistant than the ProTaper F2 file. In two-step cyclic fatigue tests, the total fatigue lives were usually more than 100% when the files operated at a lower strain and then at a higher strain. By scanning electron microscopy, a larger area of fatigue striation corresponded to a longer fatigue life. CONCLUSION: Cyclic fatigue life can be influenced by the strains and geometries of files. The fatigue life was prolonged when the files operated at a lower strain and then at a higher strain. However, the fatigue life was shortened if the loading sequence was reversed. PMID- 27375048 TI - Schneiderian membrane repair with platelet-rich fibrin during maxillary sinus augmentation with simultaneous implant placement. PMID- 27375049 TI - A study of primary hypophysitis, i.e., two cases of lymphocytic hypophysitis and one IgG4-related variant: The importance of measuring serum IgG4 levels to allow early diagnosis and prompt treatment for the IgG4-related variant. PMID- 27375050 TI - Delineation of the structural and functional role of Arg111 in GSTU4-4 from Glycine max by chemical modification and site-directed mutagenesis. AB - The structural and functional role of Arg111 in GSTU4-4 from Glycine max (GmGSTU4 4) was studied by chemical modification followed by site-directed mutagenesis. The arginine-specific reagent 2,3-butanedione (BTD) inactivates the enzyme in borate buffer at pH8.0, with pseudo-first-order saturation kinetics. The rate of inactivation exhibited a non-linear dependence on the concentration of BTD which can be described by reversible binding of reagent to the enzyme (KD 81.2+/-9.2mM) prior to the irreversible reaction, with maximum rate constants of 0.18+/ 0.01min(-1). Protection from inactivation was afforded by substrate analogues demonstrating the specificity of the reaction. Structural analysis suggested that the modified residue is Arg111, which was confirmed by protein chemistry experiments. Site-directed mutagenesis was used in dissecting the role of Arg111 in substrate binding, specificity and catalytic mechanism. The mutant Arg111Ala enzyme exhibited unchanged Km value for GSH but showed reduced affinity for the xenobiotic substrates, higher kcat and specific activities towards aromatic substrates and lower specific activities towards aliphatic substrates. The biological significance of the specific modification of Arg111 by dicarbonyl compounds and the role of Arg111 as a target for engineering xenobiotic substrate specificity were discussed. PMID- 27375051 TI - Role of conserved Met112 residue in the catalytic activity and stability of ketosteroid isomerase. AB - Ketosteroid isomerase (3-oxosteroid Delta(5)-Delta(4)-isomerase, KSI) from Pseudomonas putida catalyzes allylic rearrangement of the 5,6-double bond of Delta(5)-3-ketosteroid to 4,5-position by stereospecific intramolecular transfer of a proton. The active site of KSI is formed by several hydrophobic residues and three catalytic residues (Tyr14, Asp38, and Asp99). In this study, we investigated the role of a hydrophobic Met112 residue near the active site in the catalysis, steroid binding, and stability of KSI. Replacing Met112 with alanine (yields M112A) or leucine (M112L) decreased the kcat by 20- and 4-fold, respectively. Compared with the wild type (WT), M112A and M112L KSIs showed increased KD values for equilenin, an intermediate analogue; these changes suggest that loss of packing at position 112 might lead to unfavorable steroid binding, thereby resulting in decreased catalytic activity. Furthermore, M112A and M112L mutations reduced melting temperature (Tm) by 6.4 degrees C and 2.5 degrees C, respectively. These changes suggest that favorable packing in the core is important for the maintenance of stability in KSI. The M112K mutation decreased kcat by 2000-fold, compared with the WT. In M112K KSI structure, a new salt bridge was formed between Asp38 and Lys112. This bridge could change the electrostatic potential of Asp38, and thereby contribute to the decreased catalytic activity. The M112K mutation also decreased the stability by reducing Tm by 4.1 degrees C. Our data suggest that the Met112 residue may contribute to the catalytic activity and stability of KSI by providing favorable hydrophobic environments and compact packing in the catalytic core. PMID- 27375052 TI - Precise In Situ Modulation of Local Liquid Chemistry via Electron Irradiation in Nanoreactors Based on Graphene Liquid Cells. AB - A controlled electron-water radiolysis process is used to generate predictable concentrations of radical and ionic species in graphene liquid cells, allowing the concept of a nanoscale chemical reactor. A differential scanning technique is used to generate the desired time- and space-varying electron dose rate. Precise control of the local concentration of H2 , the dominant radiolysis species, is demonstrated experimentally at the nanometer scale. PMID- 27375053 TI - Vitamin D Kinetics and Parathyroid Gland Function in Patients with Congenital Heart Disease. AB - OBJECTIVE: It has been recently reported that vitamin D deficiency may contribute to systemic illnesses that accompany chronic heart failure. These reports also suggest the serum levels of parathormone, which activates vitamin D in the liver, can be a useful marker of heart failure. This study was designed to evaluate the clinical implications of vitamin D and parathormone levels in patients with congenital heart diseases and chronic heart failure. DESIGN: We measured 25 hydroxyvitamin D and parathormone serum levels in 103 adult patients with congenital heart diseases (age range 20-89 years). Of 103 patients, 54 were in New York Heart Association functional classes II or III. Their clinical data regarding cardiothoracic ratio, fractional shortening of the systemic ventricle, brain natriuretic peptide plasma levels, and pulse oximetry were also evaluated. RESULTS: Of 54 patients with chronic heart failure, 50 (93%) exhibited vitamin D deficiency (25-hydroxyvitamin D serum levels <50 nmol/L) or elevation of parathormone (serum levels >65 pg/mL). These two parameters were inversely correlated. In multivariate analyses including age, gender, 25-hydroxyvitamin D, parathormone, pulse oximetry, cardiothoracic ratio, calcium, phosphorus, glomerular filtration rate, albumin, creatine kinase, end-diastolic diameter and fractional shortening of the systemic ventricle, and ratio of early diastolic transmitral flow velocity to mitral annular velosity, only the parathormone serum levels (P < .01) remained independently associated with brain natriuretic peptide plasma levels. Moreover, in multivariate analyses including the same variables minus parathormone serum levels, both pulse oximetry (P < .01) and glomerular filtration rate (P < .01) remained independently associated with parathormone levels. CONCLUSIONS: Vitamin D deficiency and secondary hyperparathyroidism are common in patients with congenital heart diseases and heart failure. Serum parathormone and 25-hydroxyvitamin D levels correlated with several clinical heart failure markers, suggesting that vitamin D deficiency may deteriorate heart function in congenital heart disease patients. PMID- 27375054 TI - A dual-readout chemiluminescent-gold lateral flow test for multiplex and ultrasensitive detection of disease biomarkers in real samples. AB - Even though the gold lateral flow test (GLFT) is low-cost and allows for point-of care testing (POCT), its intrinsic limitations including low sensitivity and incapability of quantification significantly hinder the clinical application of GLFT for assaying disease biomarkers. To improve the performance of the GLFT without sacrificing its simplicity, we develop a chemiluminescent-gold lateral flow test (C-mode GLFT) for quantitative and multiplex detection of disease biomarkers with an ultrahigh sensitivity at a picomolar level. Horseradish peroxidase (HRP) and antibody (Ab) are simultaneously labeled onto the surface of gold nanoparticles (AuNPs) to achieve a dual-readout (chemiluminescent and visual, C&V-mode GLFT). A red color appears at the test line caused by the accumulation of captured AuNPs in the presence of targets, while HRP on the surface of AuNPs catalyzes the chemiluminescence reaction of luminol to amplify the signal. C-mode GLFT is successfully used for detecting tumor biomarkers (alpha fetoprotein, AFP, and carcino embryonic antigen, CEA) and bacterial infection biomarkers (procalcitonin, PCT) in serum samples as well as whole blood. The excellent features of C-mode GLFT such as straightforward operation, ultrahigh sensitivity and quantitative detection, make it a promising platform for POCT of a variety of disease biomarkers in real samples. PMID- 27375055 TI - Mutation of a conserved tryptophan residue in the CBM3c of a GH9 endoglucanase inhibits activity. AB - The presence of the family of 3c cellulose binding module (CBM3c) is important for the catalytic activity of family 9 endoglucanases such as the EngZ from Clostridium cellulovorans. To determine the role of CBM3c in catalytic activity, we made a tryptophan to alanine substitution because tryptophan can bind strongly to both substrates and other amino acids. The conserved tryptophan substitution (W483A) did not influence substrate binding, but it reduced enzyme activity to 10 14% on both amorphous and crystalline cellulose. CBM3c is directly involved in the endoglucanase reaction independent of substrate binding. EngZ W483A was also inactivated independent of substrate concentrations. Specially, EngZ W483A restored its catalytic base activity (31.6+/-1.2U/nM) which is similar to the wild-type (29.4+/-0.3U/nM) on Avicel in the presence of 50mM sodium azide which is instead of catalytic base reaction. These results suggest that CBM3c is deeply involved in the cellulolytic reaction, specifically at the catalytic base region. Moreover, EngZ W483A was also easily denatured by DTT, an outer disulfide bond breaker, compared to the wild-type. CBM3c could influence the surface stability. These features of CBM3c result from the hydrophobic interaction of tryptophan with the catalytic domain that is unrelated to substrate binding. PMID- 27375056 TI - Antitumor activity of polysaccharide from Laminaria japonica on mice bearing H22 liver cancer. AB - Water-soluble polysaccharide was extracted from Laminaria japonica, and its antitumor effect on mice bearing H22 liver cancer was investigated. The mice were inoculated with H22 hepatoma cells and randomly divided into four groups: three treatment groups that received 50, 100 and 150mg/kg L. japonica polysaccharide (LJP) intraperitoneal injection and one control group that received equal volume of physiological saline. Intraperitoneal injection of LJP increased serum interleukin-2 and tumour necrosis factor-alpha levels, as well as tumour inhibition rate of mice, but decreased serum vascular endothelial growth factor level. Therefore, LJP exerts antitumor effect and can be used as a therapeutic agent for cancer. PMID- 27375057 TI - Qualitative and quantitative composition of essential oils: A literature-based database on contact allergens used for safety assessment. AB - The risks related to the use of essential oils are difficult to ascertain at present, due in part to the large number of different oils available on the market, making it difficult for the risk assessor. Essential oils may contain skin allergens in significant amounts, and could thus pose a risk to the consumer. The aim of our study was to collect as much qualitative and quantitative data as possible on allergens present in essential oils. 11 types of essential oils, with 25 respective subspecies, were taken into account based on a previous survey. Based on the literature, 517 dosages were recorded from 112 publications, providing precious information for probabilistic exposure assessment purposes. 22 substances recognized as established allergens were found in the essential oils we included. Of these, 11 are also found in cosmetics as fragrance components. These results are of major importance regarding co-exposure to fragrance allergens. Moreover, this could lead to regulatory measures for essential oils in the future, as it is the case for cosmetic products, in order to better protect consumers against skin allergy. PMID- 27375058 TI - Improving case finding of invasive aspergillosis in children using string searches. AB - Surveillance for invasive Aspergillus (IA) in children is complex. We performed a retrospective study (2004-2013) using string searches of relevant terms within histopathology and radiology reports in efforts to improve detection of IA. Overall, 22 children met IA criteria, of whom 5 (23%) were only identified by string searches. PMID- 27375059 TI - Chlorhexidine avoids skin bacteria recolonization more than triclosan. AB - BACKGROUND: We do not know whether differences exist between the residual effect of 2% chlorhexidine in 70% isopropyl alcohol when compared with 1% triclosan in 70% isopropyl alcohol. METHODS: Using an analytic, longitudinal, controlled, and comparative experimental trial, with blinded measurements, we recruited healthy, adult volunteers from the University of Guanajuato who completed a stabilization phase of skin microbiota and had no history of skin allergies. Four 25-cm2 areas of the inner surface of the forearms were designated for study: unscrubbed control for establishing baseline bacterial counts, scrubbed control with tridistilled water, scrubbed with chlorhexidine, and scrubbed with triclosan. Quantitative cultures were taken of all the areas at 0, 3, and 24 hours, using agar plates with neutralizing agents. RESULTS: A total of 135 healthy volunteers were tested. At 24 hours, the unscrubbed control counts were 288 CFU/cm2, whereas the scrubbed control counts were 96 CFU/cm2; 24 CFU/cm2 for chlorhexidine and 96 CFU/cm2 for triclosan (Kruskal-Wallis chi2H = 64.27; P <.001). CONCLUSIONS: Chlorhexidine is the best antiseptic option when a prolonged antiseptic effect is needed; for instance, when implanting medical devices or performing surgical procedures. PMID- 27375060 TI - Does the new low-frequency ultrasonic debridement technology pose an infection control risk for clinicians, patients, and the clinic environment? AB - BACKGROUND: Low-frequency ultrasonic debridement (LFUD) is a technology that uses sound waves conducted through saline mist to debride wound tissue. Whilst this technology purportedly reduces wound-healing times, the airborne mist generated is potentially problematic. Theoretically, the saline mist could carry an increased number of microbes into the surrounding environment, posing an infection control risk to the patient, clinician, and clinical environment. This research aimed to establish the degree and extent to which there is microbial spread during the use of, and following the use of, LFUD. The total number of colony forming units was identified for use of LFUD without the suction attachment (control) and with the suction attachment (intervention). METHODS: This was a prospective, observational study with repeated measures across each treatment (before, during, and after). Quota sampling in a 2 * 2 * 2 factorial design was undertaken so that half of the 24 treatments were conducted at each health service (Monash Health vs Peninsula Health), in different treatment environments (inpatient vs outpatient), and half were conducted with and without suction. The use of suction was not randomized but was determined at the treating clinician's discretion. Patients treated in the inpatient environment lay on their beds, whereas patients in the outpatient environment sat in a treatment chair. RESULTS: There was higher microbial count during treatment (P < .001) with a higher microbial count associated with lower ultrasound amplitude (P = .028), lower saline flow rate (P = .010), no suction attachment (P = > .001), and a larger wound area (P = .002). All were independently associated with greater microorganism aerosolization. There was no correlation between the type of handpiece selected, the presence of wound infection, and the treatment time or treatment environment. CONCLUSIONS: This research has assisted in developing guidelines for cleaning of equipment and environments following treatment, as well as around the use of personal protective equipment required to protect the staff member and the patient during the use of LFUD. Additionally, recommendations have been made regarding the specific LFUD settings to reduce the risk of cross-infection to the clinic environment. These include selecting a higher ultrasound amplitude and saline flow rate as well as the use of suction where clinically possible. PMID- 27375061 TI - Perioperative hair removal in the 21st century: Utilizing an innovative vacuum assisted technology to safely expedite hair removal before surgery. AB - BACKGROUND: Perioperative hair removal using clippers requires lengthy cleanup to remove loose hairs contaminating the operative field. We compared the amount of hair debris and associated microbiologic contamination produced during clipping of surgical sites using standard surgical clippers (SSC) or clippers fitted with a vacuum-assisted hair collection device (SCVAD). METHODS: Trained nurses conducted bilateral hair clipping of the chest and groin of 18 male subjects using SSC or SCVAD. Before and during clipping, measurements of particulate matter and bacterial contamination were evaluated on settling plates placed next to each subject's chest and groin. Skin condition after clipping and total clipping/cleanup times were compared between SSC and SCVAD. RESULTS: The microbial burden recovered from residual hair during cleanup in the SSC group was 3.9 log10 CFU and 4.6 log10 CFU from respective, chest, and groin areas. Use of the SCVAD resulted in a significant (P < .001) reduction in both residual hair and microbial contamination within the operative field compared with SSC. CONCLUSIONS: Use of SCVAD resulted in significant (P < .001) reduction in total time required to clip and clean up residual hair contaminating the operative field compared with standard practice (ie, SSC), eliminating the need to physically remove dispersed hairs, which can harbor a significant microbial burden, from within the operative field. PMID- 27375062 TI - Nosocomial infection of multidrug-resistant Acinetobacter baumannii in Thailand. AB - Infections caused by Acinetobacter baumannii have become a critical problem for hospital patients worldwide. We investigated the multidrug-resistant A baumannii strain that caused hospital-acquired infections in Uthai Thani Hospital, Thailand, between 2006 and 2014. In summary, the spread of a clonally related multidrug-resistant A baumannii strain was the primary cause of nosocomial infections in Uthai Thani Hospital. PMID- 27375063 TI - Clostridium difficile-associated disease: A primary clinical evaluation of elderly patients in a geriatric hospital. AB - The purpose of this study was to screen all cases of Clostridium difficile associated disease during a 2-year period in a geriatric hospital to determine the incidence and clinical characteristics related to this risk. Twenty percent of suspected cases were diagnosed as positive and analyzed. The C difficile disease-associated clinical factors were ischemic heart disease and chronic obstructive pulmonary disease. Use of acetylsalicylic acid, other nonsteroidal anti-inflammatory drugs, and steroids were more frequently found in the non-C difficile group. There were fewer cases in men than in women and more in patients residing in skilled nursing wards. PMID- 27375064 TI - Decontamination of indoor air to reduce the risk of airborne infections: Studies on survival and inactivation of airborne pathogens using an aerobiology chamber. AB - BACKGROUND: Although indoor air can spread many pathogens, information on the airborne survival and inactivation of such pathogens remains sparse. METHODS: Staphylococcus aureus and Klebsiella pneumoniae were nebulized separately into an aerobiology chamber (24.0 m3). The chamber's relative humidity and air temperature were at 50% +/- 5% and 20 degrees C +/- 2 degrees C, respectively. The air was sampled with a slit-to-agar sampler. Between tests, filtered air purged the chamber of any residual airborne microbes. RESULTS: The challenge in the air varied between 4.2 log10 colony forming units (CFU)/m3 and 5.0 log10 CFU/m3, sufficient to show a >=3 log10 (>=99.9%) reduction in microbial viability in air over a given contact time by the technologies tested. The rates of biologic decay of S aureus and K pneumoniae were 0.0064 +/- 0.00015 and 0.0244 +/ 0.009 log10 CFU/m3/min, respectively. Three commercial devices, with ultraviolet light and HEPA (high-efficiency particulate air) filtration, met the product efficacy criterion in 45-210 minutes; these rates were statistically significant compared with the corresponding rates of biologic decay of the bacteria. One device was also tested with repeated challenges with aerosolized S aureus to simulate ongoing fluctuations in indoor air quality; it could reduce each such recontamination to an undetectable level in approximately 40 minutes. CONCLUSIONS: The setup described is suitable for work with all major classes of pathogens and also complies with the U.S. Environmental Protection Agency's guidelines (2012) for testing air decontamination technologies. PMID- 27375065 TI - FASN, dietary fat intake, and risk of uterine leiomyomata in the Black Women's Health Study. AB - OBJECTIVE: To replicate results from a previous genome-wide association study of European ancestry women, in which a positive association was found between uterine leiomyomata (UL) and rs4247357, a single-nucleotide polymorphism located near the fatty acid synthase (FASN) gene. DESIGN: Prospective cohort study. SETTING: Not applicable. PATIENT(S): African-American women aged 23-50 years, who were premenopausal and had an intact uterus in 1997. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We genotyped rs4247357 among 2,301 incident UL cases and 3,005 controls from the Black Women's Health Study (1997-2011). Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression with control for age, geographic region of residence, and percent European ancestry using a panel of validated ancestry informative markers. RESULT(S): Overall, rs4247357 was not associated with UL risk. Relative to the CC genotype, ORs were 1.04 (95% CI 0.92-1.19) for the AC genotype and 1.09 (95% CI 0.93-1.29) for the AA genotype. A positive association was found, however, among those with higher European ancestry (>=40%). Relative to the CC genotype, ORs were 2.03 (95% CI 1.12-3.69) for the AC genotype and 2.44 (95% CI 1.20-4.96) for the AA genotype. Dietary fat intake also appeared to modify the FASN-UL association. CONCLUSION(S): Although there was little overall association between rs4247357 and UL risk, a positive association was observed among women with >=40% European ancestry. Direct sequencing of this genomic region might be warranted to determine whether rs4247357, or some other variant, is causally related to UL. PMID- 27375066 TI - Comparison of Compass and Humphrey perimeters in detecting glaucomatous defects. AB - PURPOSE: To compare the performance of Compass fundus automated perimetry (FAP) and Humphrey Field Analyzer (HFA) in glaucoma patients. METHODS: A total of 120 patients with glaucoma underwent 1 FAP and 1 HFA perimetric test over the central 24 degrees on one eye. The chosen eye and sequence were randomized and only reliable examinations were considered for analysis. Mean deviation (MD), pattern standard deviation (PSD), visual field index (VFI), and the area of absolute scotoma were compared between perimeters. Glaucoma Staging System (GSS2) data were analyzed by means of k test. RESULTS: Mean sensitivity difference (FAP-HFA) was -1.0 +/- 2.81 dB (p<0.001, 95% confidence interval [CI] -1.61, -0.60 dB), MD difference was +0.27 +/- 2.84 dB (p = 0.36, 95% CI -5.30, 5.83 dB), PSD difference was +0.48 +/- 1.95 dB (p = 0.0075, 95% CI -3.37, 4.33 dB), and VFI difference was +2.4% +/- 8.4% (p = 0.003, 95% CI -14.0%, +18.8% dB). Weighted kappa for GSS2 was 0.87. Points with null sensitivities were 9.9 +/- 10.2 with FAP and 8.2 +/- 8.9 with HFA (difference: 1.7 +/- 4.0 points, p = 0.013). CONCLUSIONS: Mean sensitivity with FAP is 1 dB lower than HFA, a finding due to different threshold strategies. Differences of global indices for FAP and HFA are small, which makes the 2 perimeters equivalent in the clinical setting. However, FAP seems more severe in evaluating glaucomatous damage, with absolute scotoma areas larger than with HFA. We raise the hypothesis that such difference may be the result of the active compensation of eye movements available with FAP. PMID- 27375067 TI - Morphologic changes in the anterior segment using ultrasound biomicroscopy after cataract surgery and intraocular lens implantation. AB - PURPOSE: To evaluate morphologic changes in the anterior segment using ultrasound biomicroscopic imaging (UBM) after phacoemulsification and foldable intraocular lens implantation (IOL). METHODS: Thirty-six patients with a mean age of 68.68 +/ 8.44 years (range 51-89) who had phacoemulsification and foldable IOL implantation were included in this prospective study. Several anterior segment parameters including aqueous depth (AQD), trabecular meshwork-iris angle (TIA), ciliary body thickness (CBT), sclera thickness (ST), trabecular meshwork-ciliary process distance (T-CPD), iris-ciliary processes distance (I-CPD), and iris thickness (IT) were measured using UBM preoperatively and at postoperative month 2. RESULTS: There was a significant increase in AQD (p<0.001) and TIA (p<0.001) at postoperative month 2. However, CBT, ST, T-CPD, I-CPD, and IT did not significantly change (p>0.05) during the study period. CONCLUSIONS: Removal of the crystalline lens results in change in the anterior segment parameters. Our results confirmed that UBM is a helpful option for the analysis of anterior segment structures both qualitatively and quantitatively. PMID- 27375068 TI - Etiology and treatment of choroidal neovascularization in pediatric patients. AB - PURPOSE: To assess the etiology, clinical features, and outcome of choroidal neovascularization (CNV) in children. METHODS: We retrospectively assessed 10 eyes of 8 patients younger than 18 years diagnosed with CNV. The main clinical parameters included predisposing ocular pathologies, best-corrected visual acuity before and after treatment, characteristics of CNV, and treatment modalities. RESULTS: Two boys and 6 girls with CNV and a mean age of 13.9 years (SD 1.9, range 11-16 years) were included. Two patients developed bilateral CNV within the follow-up time. The development of CNV was secondary to the following pathologies: choroidal osteoma (n = 3), pathologic myopia (n = 1), punctate inner choroidopathy (n = 1), hereditary macular dystrophy (n = 2), and angioid streaks (n = 1). Idiopathic CNV was diagnosed in 2 children without any obvious associated ocular pathology. In 9 eyes, CNV was treated by intravitreal anti vascular endothelial growth factor (VEGF) administration (n = 6), photodynamic therapy (n = 1), or combination therapy (n = 3). One eye remained untreated because of advanced disease. CONCLUSIONS: Pediatric CNV is a rare but sight threatening retinal disease. So far, no standard treatment has been validated. Since the establishment of intravitreal anti-VEGF therapy, laser coagulation and photodynamic therapy have lost their significance as therapy for CNV. PMID- 27375069 TI - Photopic and Mesopic Performance of 2 Different Trifocal Diffractive Intraocular Lenses. AB - Purpose To assess photopic and mesopic vision in patients implanted with 2 different trifocal intraocular lenses (IOLs). Methods Fifty patients with cataract in both eyes had surgery with bilateral implantation of a trifocal FineVision (FV, n = 25) or AT LISA tri 839MP (LisaTri, n = 25) IOL. Three months after surgery, high-contrast photopic uncorrected distance visual acuity and corrected distance visual acuity (CDVA) were determined using the Early Treatment Diabetic Retinopathy Study test. Intermediate (65 cm) and near (40 cm) visual acuity were also measured, both with best distance correction (DCIVA and DCNVA, respectively). The CSV1000 test chart was used for binocular and monocular contrast sensitivity. Defocus curves were constructed under photopic and mesopic conditions. Results Mean patient age was 68.4 +/- 5.5 years (FV) and 67.3 +/- 5.6 years (LisaTri) (p = 0.540). No differences were found in terms of visual acuity between the groups. The CDVA, DCIVA, and DCNVA were 0.05 +/- 0.06, 0.25 +/- 0.10, and 0.13 +/- 0.10 logMAR for FV and -0.04 +/- 0.11, 0.32 +/- 0.09, and 0.12 +/- 0.11 logMAR for LisaTri, respectively (p = 0.09, p = 0.08, and p = 0.12). Photopic and mesopic defocus curves were comparable between the 2 IOL groups (p>0.05). Mesopic values were significantly worse than photopic in both groups for all the measured values (p<0.001). No differences in contrast sensitivity were observed between the 2 IOL groups (p>0.05). Conclusions Both trifocal diffractive IOLs provided good visual quality with a statistically significant decrease in mesopic conditions. PMID- 27375070 TI - Leukemia inhibitory factor receptor negatively regulates the metastasis of pancreatic cancer cells in vitro and in vivo. AB - Pancreatic cancer (PC) is one of the leading causes of cancer-related deaths worldwide. Frequent metastasis and recurrence are the main reasons for the poor prognosis of PC patients. Thus, the discovery of new biomarkers and wider insights into the mechanisms involved in pancreatic tumorigenesis and metastasis is crucial. In the present study, we report that leukemia inhibitory factor receptor (LIFR) suppresses tumorigenesis and metastasis of PC cells both in vitro and in vivo. LIFR expression was significantly lower in PC tissues and was associated with local invasion (P=0.047), lymph node metastasis (P=0.014) and tumor-node-metastasis (TNM) stage (P=0.002). Overexpression of LIFR significantly suppressed PC cell colony formation (P=0.005), migration (P=0.003), invasion (P=0.010) and wound healing ability (P=0.013) in vitro, while opposing results were observed after LIFR was silenced. Furthermore, animal xenograft and metastasis models confirm that the in vivo results were consistent with the outcomes in vitro. Meanwhile, LIFR inhibited the expression of beta-catenin, vimentin and slug and induced the expression of E-cadherin, suggesting that the epithelial-mesenchymal transition regulation pathway may underlie the mechanism. These results indicate that LIFR negatively regulates the metastasis of PC cells. PMID- 27375071 TI - Risk Factors for Removal or Revision of Penile Prostheses in the Veteran Population. AB - OBJECTIVE: To identify comorbid conditions that may increase the likelihood of revision surgery after primary penile prosthesis implantation. To evaluate trends in utilization of prostheses and selection of device within the Veterans Affairs (VA) system. METHODS: A retrospective review of the VA Informatics and Computing Infrastructure database was performed using Current Procedural Technology codes to identify any Veteran who underwent penile prosthesis surgery between January 2000 and December 2013. Age, race, procedure type, and relevant comorbidities were identified and compared between groups. RESULTS: A total of 6586 patients underwent primary penile prosthesis placement with at least 1 year of follow-up. Peripheral vascular disease (P <.001), smoking (P <.001), hypertension (P = .012), and history of prostate cancer (P = .043) were each associated with a significant increased risk of revision or removal surgery. There was an increase in overall number of implants placed during the study and increased durability with malleable penile prosthesis (MPP), but there was a downward trend in the number of MPP placed relative to inflatable penile prosthesis (P <.001). MPP were more likely to be placed with increasing age (P <.05) and there was a trend toward increased MPP placement in African Americans compared with Caucasians (P = .06). CONCLUSION: Peripheral vascular disease, hypertension, smoking, and history of prostate cancer are associated with increased risk for secondary surgery. This raises a provocative question of how vascular insufficiency may play a role in the likelihood of secondary surgery after penile prosthesis placement. Utilization of penile prosthesis placement in the VA system is steadily increasing, most notably with increased numbers of inflatable penile prosthesis placement. PMID- 27375072 TI - Does DCD Donor Time-to-Death Affect Recipient Outcomes? Implications of Time-to Death at a High-Volume Center in the United States. AB - For donation after circulatory death (DCD), many centers allow 1 h after treatment withdrawal to donor death for kidneys. Our center has consistently allowed 2 h. We hypothesized that waiting longer would be associated with worse outcome. A single-center, retrospective analysis of DCD kidneys transplanted between 2008 and 2013 as well as a nationwide survey of organ procurement organization DCD practices were conducted. We identified 296 DCD kidneys, of which 247 (83.4%) were transplanted and 49 (16.6%) were discarded. Of the 247 recipients, 225 (group 1; 91.1%) received kidneys with a time to death (TTD) of 0 1 h; 22 (group 2; 8.9%) received grafts with a TTD of 1-2 h. Five-year patient survival was 88.8% for group 1, and 83.9% for group 2 (p = 0.667); Graft survival was also similar, with 5-year survival of 74.1% for group 1, and 83.9% for group 2 (p = 0.507). The delayed graft function rate was the same in both groups (50.2% vs. 50.0%, p = 0.984). TTD was not predictive of graft failure. Nationally, the average maximum wait-time for DCD kidneys was 77.2 min. By waiting 2 h for DCD kidneys, we performed 9.8% more transplants without worse outcomes. Nationally, this practice would allow for hundreds of additional kidney transplants, annually. PMID- 27375073 TI - Defining the Performance Parameters of a Rapid Screening Tool for FMR1 CGG-Repeat Expansions Based on Direct Triplet-Primed PCR and Melt Curve Analysis. AB - Population-based screening for CGG-repeat expansions in the fragile X mental retardation 1 (FMR1) gene that cause fragile X syndrome can now be performed more cost-effectively and simply by combining direct triplet-primed PCR (dTP-PCR) with melting curve analysis (MCA). We have now performed a detailed technical validation to define the operational parameters for achieving robust and reliable performance of the FMR1 dTP-PCR MCA assay. We compared the assay's performance on 2 real-time PCR platforms and determined its analytic sensitivity and specificity. We also assessed the assay's performance on DNA isolated from different sources, the effect of differences in CGG-repeat length and AGG interruption pattern on melt peak temperature (Tm), and the effect of common substances found in DNA solutions on Tms. The assay performed well in distinguishing normal from expansion-carrying samples. The assay had detection sensitivity down to 1 ng and an analytical specificity beyond 150 ng. In addition to peripheral blood DNA, analysis could also be performed on DNA from saliva, buccal swabs, and dried blood spots. Salt increased Tms, glycogen contamination had minimal effect, whereas AGG interruptions lowered Tms. The FMR1 dTP-PCR MCA screening assay is highly sensitive and specific, performs well using DNA from different sources, and is robust and reproducible when reagent concentrations are maintained across all tested samples. PMID- 27375075 TI - Extracellular vesicles in renal tissue damage and regeneration. AB - Extracellular vesicles (EVs) appear as important actors in cell-to-cell communication. EV content is characterized by proteins and RNA species that dynamically reflect cell and tissue state. Urinary EVs in particular may act in inter-nephron communication with possible beneficial or detrimental effects. Increasing interest is addressed to the pharmacological properties of EVs as a cell-free therapy, since several of the effects crAQ/tgqcedited to stem cells have been recapitulated by administration of their EVs. Preclinical data in models of renal damage indicate a general regenerative potential of EVs derived from mesenchymal stromal cells of different sources, including bone marrow, fetal tissues, urine and kidney. In this review we will discuss the results on the effect of EVs in repair of acute and chronic renal injury, and the mechanisms involved. In addition, we will analyse the strategies for EV pharmacological applications in renal regenerative medicine and limits and benefits involved. PMID- 27375074 TI - Reality of Single Circulating Tumor Cell Sequencing for Molecular Diagnostics in Pancreatic Cancer. AB - To understand the potential and limitations of circulating tumor cell (CTC) sequencing for molecular diagnostics, we investigated the feasibility of identifying the ubiquitous KRAS mutation in single CTCs from pancreatic cancer (PC) patients. We used the NanoVelcro/laser capture microdissection CTC platform, combined with whole genome amplification and KRAS Sanger sequencing. We assessed both KRAS codon-12 coverage and the degree that allele dropout during whole genome amplification affected the detection of KRAS mutations from single CTCs. We isolated 385 single cells, 163 from PC cell lines and 222 from the blood of 12 PC patients, and obtained KRAS sequence coverage in 218 of 385 single cells (56.6%). For PC cell lines with known KRAS mutations, single mutations were detected in 67% of homozygous cells but only 37.4% of heterozygous single cells, demonstrating that both coverage and allele dropout are important causes of mutation detection failure from single cells. We could detect KRAS mutations in CTCs from 11 of 12 patients (92%) and 33 of 119 single CTCs sequenced, resulting in a KRAS mutation detection rate of 27.7%. Importantly, KRAS mutations were never found in the 103 white blood cells sequenced. Sequencing of groups of cells containing between 1 and 100 cells determined that at least 10 CTCs are likely required to reliably assess KRAS mutation status from CTCs. PMID- 27375076 TI - Aptamer BC 007 - A broad spectrum neutralizer of pathogenic autoantibodies against G-protein-coupled receptors. AB - The effect of autoantibodies on G-protein coupled receptors in the pathogenesis of diseases, especially of the heart and vascular system, is an increasingly accepted fact today. Dilated cardiomyopathy (DCM) is the most intensively investigated pathological situation of these. With DCM, autoantibodies against the beta1-adrenoceptor and the muscarinic M2-receptor have been found in high percentage of investigated patients. Immunoadsorption for autoantibody removal has already shown a long-term beneficial therapeutic effect, but has remained limited in its application because of the complexity of this method. A new easy applicable treatment strategy has, therefore, been discovered. Because of intra- and inter-loop epitope variability of the beta1-adrenoceptor specific autoantibodies and also the occurrence of further autoantibodies of this class such as the ones against the beta2- and alpha1-adrenoceptor, the ETA-, proteinase activated-, and the AT1-receptors in different pathological situations, this newly discovered broad-spectrum neutralizer of all these autoantibodies - aptamer BC 007 - is under development. The binding and neutralizing effect was investigated applying a bioassay of spontaneously beating neonatal rat cardiomyocytes and enzyme-linked immunosorbent assay (ELISA) - technology. The usefulness of aptamer BC 007 to specify column technology for the removal of serum autoantibodies was also demonstrated. The presented data suggest that aptamer BC 007 might be an appropriate molecule candidate to support future research about the meaning of G-protein-coupled receptor autoantibodies. PMID- 27375078 TI - Renal fibrosis in precision-cut kidney slices. AB - Chronic kidney disease (CKD) is associated with renal fibrosis, a pathological process that is characterized by excessive accumulation of extracellular matrix proteins resulting in loss of organ architecture and function. Currently, renal transplantation and dialysis are the sole treatment options for advanced CKD, yet these therapies have limited impact on fibrogenesis. Even though antifibrotic therapies are being developed, the search for effective antifibrotic drugs is being hampered by the lack of appropriate cell and animal models to study renal fibrosis. In vitro models lack cellular heterogeneity whereas in vivo models do not fully reflect human pathology. Precision-cut tissue slices, prepared from human or rodent tissue, provide a unique ex vivo model system that captures the complexity of organs, and they are widely used for ADME/Tox drug testing. Moreover, precision-cut kidney slices (PCKS) have been recently established as a useful model to study renal fibrosis. This review summarizes the currently available models for renal fibrosis, describes the wide array of possibilities with PCKS and shows its role in the search for antifibrotic drugs. PMID- 27375077 TI - Imaging technologies for monitoring the safety, efficacy and mechanisms of action of cell-based regenerative medicine therapies in models of kidney disease. AB - The incidence of end stage kidney disease is rising annually and it is now a global public health problem. Current treatment options are dialysis or renal transplantation, which apart from their significant drawbacks in terms of increased morbidity and mortality, are placing an increasing economic burden on society. Cell-based Regenerative Medicine Therapies (RMTs) have shown great promise in rodent models of kidney disease, but clinical translation is hampered due to the lack of adequate safety and efficacy data. Furthermore, the mechanisms whereby the cell-based RMTs ameliorate injury are ill-defined. For instance, it is not always clear if the cells directly replace damaged renal tissue, or whether paracrine effects are more important. Knowledge of the mechanisms responsible for the beneficial effects of cell therapies is crucial because it could lead to the development of safer and more effective RMTs in the future. To address these questions, novel in vivo imaging strategies are needed to monitor the biodistribution of cell-based RMTs and evaluate their beneficial effects on host tissues and organs, as well as any potential adverse effects. In this review we will discuss how state-of-the-art imaging modalities, including bioluminescence, magnetic resonance, nuclear imaging, ultrasound and an emerging imaging technology called multispectral optoacoustic tomography, can be used in combination with various imaging probes to track the fate and biodistribution of cell-based RMTs in rodent models of kidney disease, and evaluate their effect on renal function. PMID- 27375079 TI - An introduction to the pharmacology of kidney regeneration. PMID- 27375080 TI - Propyl gallate sensitizes human lung cancer cells to cisplatin-induced apoptosis by targeting heme oxygenase-1 for TRC8-mediated degradation. AB - Heme oxygenase-1 (HO-1) significantly contributes to survival of cancer cells and is being considered as one of therapeutic targets for cancer treatment. Propyl gallate (PG) is a synthetic phenolic compound that possess a potent anti-oxidant and anti-inflammatory activities. In the present study, we investigated whether PG exhibit an anti-cancer effect through modulating HO-1 activation. In human non small cell lung cancer (NSCLC) cells, treatment with PG dose-dependently diminished HO-1 protein levels without changing its mRNA levels and consequently decreased HO-1 activity. PG also significantly enhanced the sensitivity of NSCLC cells to cisplatin-induced apoptosis, and this effect was attenuated by overexpression of HO-1. Mechanistically, PG exerted its chemosensitization effect by down-regulating HO-1 protein expression through a TRC8 (translocation in renal carcinoma, chromosome 8)-mediated ubiquitin-proteasome pathway. Collectively, our data provide the potential application of PG in combination chemotherapy to enhance drug sensitivity in lung cancer by targeting HO-1. PMID- 27375081 TI - Pluripotent stem cell-derived kidney organoids: An in vivo-like in vitro technology. AB - Organoids are self-organizing, multicellular structures that contain multiple cell types, represent organ structure and function, and can be used to model organ development, maintenance and repair ex vivo. Organoids, derived from embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) or adult stem cells, are cultured in extracellular matrix (ECM). Organoid cultures have been developed for multiple organs and for the kidney, pluripotent stem cell (PSCs) derived organoid technology has rapidly developed in the last three years. Here, we review available PSC differentiation protocols, focusing on the pluripotent stem cells to initiate the organoid culture, as well as on growth factors and ECM used to regulate differentiation and expansion. In addition, we will discuss the read out strategies to evaluate organoid phenotype and function. Finally, we will indicate how the choice of both culture parameters and read out strategy should be tailored to specific applications of the organoid culture. PMID- 27375083 TI - Preventing work-related stress among staff working in children's cancer Principal Treatment Centres in the UK: a brief survey of staff support systems and practices. AB - Growing evidence of the association between health professionals' well-being and patient and organisational outcomes points to the need for effective staff support. This paper reports a brief survey of the UK's children's cancer Principal Treatment Centres (PTCs) regarding staff support systems and practices. A short on-line questionnaire, administered in 2012-2013, collected information about the availability of staff support interventions which seek to prevent work related stress among different members of the multi-disciplinary team (MDT). It was completed by a member of staff with, where required, assistance from colleagues. All PTCs (n = 19) participated. Debriefs following a patient death was the most frequently reported staff support practice. Support groups were infrequently mentioned. There was wide variability between PTCs, and between professional groups, regarding the number and type of interventions available. Doctors appear to be least likely to have access to support. A few Centres routinely addressed work-related stress in wider staff management strategies. Two Centres had developed a bespoke intervention. Very few Centres were reported to actively raise awareness of support available from their hospital's Occupational Health department. A minority of PTCs had expert input regarding staff support from clinical psychology/liaison psychiatry. PMID- 27375084 TI - Intercellular transfer of P-glycoprotein in human blood-brain barrier endothelial cells is increased by histone deacetylase inhibitors. AB - The blood-brain barrier (BBB) controls the entry of compounds into the brain, thereby regulating brain homeostasis. Efflux transporters such as P-glycoprotein (Pgp) significantly contribute to BBB function. Multiple signaling pathways modulate the expression and activity of Pgp in response to xenobiotics and disease. A non-genetic way of intercellular transfer of Pgp occurs in cancer cells, but whether this also occurs in non-cancer cells such as endothelial cells that form the BBB is not known. A human brain endothelial cell line (hCMEC/D3) was used to study whether cell-to-cell Pgp transfer occurs during co-culturing with Pgp-EGFP expressing hCMEC/D3 cells. The Pgp-EGFP fusion protein was transferred from donor to recipient cells by cell-to-cell contact and Pgp-EGFP enriched vesicles, which were exocytosed by donor cells and endocytosed by adherent recipient cells. Flow cytometry experiments with the Pgp substrate eFLUXX-ID Gold demonstrated that the transferred Pgp is functional in the recipient cells. Exposure of the donor cells with inhibitors of histone deacetylases (HDACs) resulted in an enhanced intercellular Pgp transfer. Non genetic transfer of a resistance phenotype and its regulation by HDACs is a novel mechanism of altering BBB functionality. This mechanism may have important implications for understanding drug-induced alterations in Pgp expression and activity. PMID- 27375085 TI - Anatomical constraints to C4 evolution: light harvesting capacity in the bundle sheath. AB - In C4 photosynthesis CO2 assimilation and reduction are typically coordinated across mesophyll (M) and bundle sheath (BS) cells, respectively. This system consequently requires sufficient light to reach BS to generate enough ATP to allow ribulose-1,5-bisphosphate (RuBP) regeneration in BS. Leaf anatomy influences BS light penetration and therefore constrains C4 cycle functionality. Using an absorption scattering model (coded in Excel, and freely downloadable) we simulate light penetration profiles and rates of ATP production in BS across the C3 , C3 -C4 and C4 anatomical continua. We present a trade-off for light absorption between BS pigment concentration and space allocation. C3 BS anatomy limits light absorption and benefits little from high pigment concentrations. Unpigmented BS extensions increase BS light penetration. C4 and C3 -C4 anatomies have the potential to generate sufficient ATP in the BS, whereas typical C3 anatomy does not, except some C3 taxa closely related to C4 groups. Insufficient volume of BS, relative to M, will hamper a C4 cycle via insufficient BS light absorption. Thus, BS ATP production and RuBP regeneration, coupled with increased BS investments, allow greater operational plasticity. We propose that larger BS in C3 lineages may be co-opted for C3 -C4 and C4 biochemistry requirements. PMID- 27375086 TI - Early prediction of systematic inflammatory response syndrome (SIRS) after major thoracic operation should not be sneezed at, but it is not a panacea. PMID- 27375087 TI - Functional status, age, and long-term survival after trauma. AB - BACKGROUND: The association between functional status in trauma survivors and long-term outcomes is unknown. METHODS: We performed an observational cohort study on adult trauma patients (>=18 years), who required admission to the intensive care unit and who survived hospitalization between 1997 and 2011. The exposure of interest was a functional status defined as bed mobility, transfers, and gait level assessed at the time of hospital discharge. Adjusted odds ratios were estimated by multivariable logistic regression models. The primary outcome was all-cause, postdischarge mortality. RESULTS: We analyzed 3,565 patients with a mean (standard deviation) age of 55 (12.4) years; 60% were male, and 78% were white. The 720-day postdischarge mortality was 22.8%. In a logistic regression model, the lowest functional status category at hospital discharge was associated with 4-fold increased odds of 720-day postdischarge mortality (adjusted odds ratio 4.06 (95% confidence interval, 2.65-6.20, P < .001) compared with patients with independent functional status. We compared the odds of 720-day postdischarge mortality in patients with independent functional status and in patients in the lowest functional status category at hospital discharge. The odds of 720-day postdischarge mortality were stronger in older adults (>=65 years: adjusted odds ratio 3.34 [95% confidence interval, 1.72-6.50, P < .001]) than in younger adults (<65 years: adjusted odds ratio 2.53 [95% confidence interval, 1.39-4.60, P = .002]). Finally, improvement of functional status prior to discharge was associated with a 52% decrease in the odds of 720-day postdischarge mortality (adjusted odds ratio 0.48; 95% confidence interval, 0.30-0.75; P < .001) compared with patients without a change in functional status prior to discharge. CONCLUSION: In trauma intensive care unit survivors, functional status at hospital discharge is predictive of long-term mortality. PMID- 27375088 TI - Response to: "Modified associating liver partition and portal vein occlusion for a staged hepatectomy procedure with right anterior liver sector congestion: Friend or foe?". PMID- 27375090 TI - The Norwegian versions of the Chronic Pain Acceptance Questionnaire CPAQ-20 and CPAQ-8 - validation and reliability studies. AB - PURPOSE: The aim of this study was to test the validity and reliability of the translated Norwegian version of the Chronic Pain Acceptance Questionnaire (CPAQ 20) and the shorter version CPAQ-8 based on the same data. METHOD: The sample consisted of 120 women with chronic widespread musculoskeletal pain (CWP). The respondents completed CPAQ-20 and visual analogue scales (pain, fatigue, sleep problems and depression), General Health Questionnaire-12, The Pain Catastrophizing Scale, Fibromyalgia Impact Questionnaire and SF-8. Confirmatory factor analyses were performed on a one-factor baseline model, the previous validated CPAQ-20 and CPAQ-8 models, as well as an exploratory generated model based on the current sample. RESULTS: The two-factor model of CPAQ-20 and a two factor model of CPAQ-8 obtained adequate model fit and outperformed the baseline model. The exploratory factor, analysis-generated two-factor model obtained only a marginally better fit, supporting the two-dimensional model of CPAQ-20. CPAQ-20 and CPAQ-8 had Cronbach's alphas between 0.75 (Pain Willingness subscales both versions) and 0.85. Both scales correlated significantly in the hypothesised direction with all the other scales. CONCLUSION: The Norwegian versions of CPAQ 20 and CPAQ-8 are reliable assessment tools with good construct validity for measurement of acceptance. Future studies should validate the scales in other Norwegian samples. Implication for Rehabilitation CPAQ-20 and CPAQ-8 are valid Norwegian instruments for measuring acceptance of pain. Acceptance of pain is an important process in the rehabilitation of persons with chronic widespread pain. Treatment models supporting acceptance can now be developed and measured further in Norway. PMID- 27375089 TI - Observations of movement dynamics of flying insects using high resolution lidar. AB - Insects are fundamental to ecosystem functioning and biodiversity, yet the study of insect movement, dispersal and activity patterns remains a challenge. Here we present results from a novel high resolution laser-radar (lidar) system for quantifying flying insect abundance recorded during one summer night in Sweden. We compare lidar recordings with data from a light trap deployed alongside the lidar. A total of 22808 insect were recorded, and the relative temporal quantities measured matched the quantities recorded with the light trap within a radius of 5 m. Lidar records showed that small insects (wing size <2.5 mm(2) in cross-section) moved across the field and clustered near the light trap around 22:00 local time, while larger insects (wing size >2.5 mm(2) in cross-section) were most abundant near the lidar beam before 22:00 and then moved towards the light trap between 22:00 and 23:30. We could distinguish three insect clusters based on morphology and found that two contained insects predominantly recorded above the field in the evening, whereas the third was formed by insects near the forest at around 21:30. Together our results demonstrate the capability of lidar for distinguishing different types of insect during flight and quantifying their movements. PMID- 27375091 TI - Immobilization of chlorophyll by using layer-by-layer technique for controlled release systems and photodynamic inactivation. AB - The development of systems for the controlled release of drugs is important because they allow the control of drug absorption and tissue distribution and also can reduce local toxicity. This study aimed to assemble and characterize two types of release systems, consisting of layer-by-layer films obtained from poly(allylamine) hydrochloride with chlorophyll (PAH/CHL films) or chlorophyll incorporated into dipalmitoylphosphatidylcholine liposomes (PAH/Lip+CHL films). For these systems, the molecular aggregation, growth process, thermally stimulated desorption, wettability, and controlling release of CHL was studied by using UV-vis spectroscopy and wetting contact angle analysis. In addition, experiments of photodynamic inactivation using PAH/CHL or PAH/Lip+CHL films with a 633-nm laser light were performed and the susceptibility of Candida albicans (C. albicans) to this approach was examined. Fluorescence and atomic force microscopies were used to investigate the surface morphology after the application of the photoinactivation procedure. A redshift of the UV-vis spectrum associated to films when compared with the spectrum of the CHL solution indicated a molecular aggregation of CHL molecules in the films. The film growth process was determined by a nucleation and a growth of spheroids or rods for either PAH/Lip+CHL or PAH/CHL films, respectively. Thermally activated desorption experiments indicated that interactions between CHL and PAH (126kJ/mol) in PAH/CHL or between Lip+CHL and PAH (140kJ/mol) in PAH/Lip+CHL films may be governed by electrostatic interactions. The wettability of PAH/Lip+CHL films was larger than that for PAH/CHL films, which can be attributed to hydrophilic groups on the surface of the DPPC liposomes. Release experiments revealed that free CHL in PAH/CHL films was released more slowly than its partner incorporated into liposomes. After the photodynamic inactivation, results of survival fraction and fluorescence microscopy revealed that C. albicans presented similar susceptibility for the two kinds of films. AFM supported the fluorescence one suggesting that cell death of C. albicans may occur due to damages to its cell wall by C. albicans. PMID- 27375093 TI - Editorial: serologic microbial-associated markers to predict Crohn's disease behaviour. PMID- 27375094 TI - Editorial: serologic microbial associated markers to predict Crohn's disease behaviour - authors' reply. PMID- 27375092 TI - IL-22 exacerbates weight loss in a murine model of chronic pulmonary Pseudomonas aeruginosa infection. AB - BACKGROUND: Interleukin (IL)-22 is a critical mediator of mucosal immunity and tissue regeneration, protecting against a number of respiratory pathogens. Whether IL-22 confers protection against chronic Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) is unknown. METHODS: Explanted CF lungs were examined for IL-22 production and immune-localization. A murine model of persistent pulmonary PA infection was used to examine production of IL-22 following infective challenge. The role of IL-22 was examined using IL-22 knockout (KO) animals. RESULTS: IL-22 is produced within the adult CF lung and localizes to the airway epithelium. IL-22 is produced by murine pulmonary lymph node cells following lung infection. The absence of IL-22 resulted in no significant difference in acute mortality, bacterial burden, chronic infection rates, histological changes or neutrophilic inflammation in the chronic PA infection model. However, IL-22 KO animals lost less weight following infection. CONCLUSION: IL-22 is produced in the CF lung and in response to PA infection yet is dispensable in protection against chronic pulmonary P. aeruginosa infection in a murine model. However, we identified a novel role for the cytokine in promoting infection-related weight-loss, a significant prognostic factor in the CF population. PMID- 27375095 TI - Editorial: mixed soluble fibre in chronic constipation - something new? PMID- 27375096 TI - Editorial: mixed soluble fibre in chronic constipation - something new? Authors' reply. PMID- 27375097 TI - Letter: probing the consequences of potent acid inhibition by vonoprazan. PMID- 27375098 TI - Letter: probing the consequences of potent acid inhibition by vonoprazan - authors' reply. PMID- 27375099 TI - Letter: hydroxypropyl cellulose as therapy for chronic diarrhoea in patients with bile acid malabsorption - possible mechanisms. PMID- 27375100 TI - Letter: the therapeutic potential of targeting CCL25/CCR9 in colonic inflammatory bowel disease - reading between the lines. PMID- 27375101 TI - Letter: irritable bowel syndrome-type symptoms in paediatric inflammatory bowel disease. PMID- 27375102 TI - Letter: irritable bowel syndrome-type symptoms in paediatric inflammatory bowel disease - authors' reply. PMID- 27375103 TI - Letter: a prospective real life comparison of the efficacy of adalimumab vs. golimumab in moderate to severe ulcerative colitis. PMID- 27375104 TI - Transoral robotic surgery for oropharyngeal cancer. PMID- 27375105 TI - Progression-free survival with regorafenib in gastric cancer. PMID- 27375106 TI - The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin. AB - OBJECTIVE: SCN8A encephalopathy (early infantile epileptic encephalopathy; EIEE13) is caused by gain-of-function mutations resulting in hyperactivity of the voltage-gated sodium channel Nav 1.6. The channel is concentrated at the axon initial segment (AIS) and is involved in establishing neuronal excitability. Clinical features of SCN8A encephalopathy include seizure onset between 0 and 18 months of age, intellectual disability, and developmental delay. Seizures are often refractory to treatment with standard antiepileptic drugs, and sudden unexpected death in epilepsy (SUDEP) has been reported in approximately 10% of patients. In a recent study, high doses of phenytoin were effective in four patients with SCN8A encephalopathy. In view of this observation, we have investigated the relationship between the functional effect of the SCN8A mutation p.Ile1327Val and its response to phenytoin. METHODS: The mutation was introduced into the Scn8a cDNA by site-directed mutagenesis. Channel activity was characterized in transfected ND7/23 cells. The effects of phenytoin (100 MUm) on mutant and wild-type (WT) channels were compared. RESULTS: Channel activation parameters were shifted in a hyperpolarizing direction in the mutant channel, whereas inactivation parameters were shifted in a depolarizing direction, increasing Na channel window current. Macroscopic current decay was slowed in I1327V channels, indicating an impairment in the transition from open state to inactivated state. Channel deactivation was also delayed, allowing more channels to remain in the open state. Phenytoin (100 MUm) resulted in hyperpolarized activation and inactivation curves as well as greater tonic block and use dependent block of I1327V mutant channels relative to WT. SIGNIFICANCE: SCN8A - I1327V is a gain-of-function mutation with altered features that are predicted to increase neuronal excitability and seizure susceptibility. Phenytoin is an effective inhibitor of the mutant channel and may be of use in treating patients with gain-of-function mutations of SCN8A. PMID- 27375108 TI - Management of Graves' disease during pregnancy in the Poitou-Charentes Region. AB - : Graves' disease (GD) during pregnancy involves risks for the mother, foetus and neonate. OBJECTIVE: To compile an inventory of the clinical practices regarding the management of GD during pregnancy in the Poitou-Charentes region of France. This was a retrospective, multicentre study covering the period 2005 to 2012. Ninety-five pregnancies were reviewed: 14 GD diagnosed during pregnancy, 24 GD already treated with synthetic antithyroid drugs (SAT) prior to pregnancy, 25 GD in remission before pregnancy and 32 GD who had undergone thyroidectomy prior to pregnancy. In patients under SAT and/or with TSH receptor antibody levels (TRAb)>3N at the 2nd (T2) and/or 3rd trimester (T3) of pregnancy, a foetal thyroid ultrasound (FTU) was performed in 18/32 cases and neonatal thyroid screening (NTS) in 14/20 cases. One case of foetal hyperthyroidism, two of neonatal hyperthyroidism and three of foetal hypothyroidism (including one neonatal hypothyroidism) were observed. Propylthiouracil was the preferred treatment prescribed, whatever the trimester. A congenital malformation was observed in 4/19 foetuses exposed to carbimazole during the 1st trimester (T1). In operated patients, TSH levels were>2.5mIU/L during T1 in 23/32 cases, while TRAb were not assayed during pregnancy in 12/32 cases. The management of GD during pregnancy could be improved by adjusting SAT therapy during its course, titrating levothyroxine prior to conception and in early pregnancy in thyroidectomised patients, and a more targeted use of FTU during T2 and T3 and of neonatal thyroid screening. PMID- 27375107 TI - Antisense antimicrobial therapeutics. AB - Antisense antimicrobial therapeutics are synthetic oligomers that silence expression of specific genes. This specificity confers an advantage over broad spectrum antibiotics by avoiding unintended effects on commensal bacteria. The sequence-specificity and short length of antisense antimicrobials also pose little risk to human gene expression. Because antisense antimicrobials are a platform technology, they can be rapidly designed and synthesized to target almost any microbe. This reduces drug discovery time, and provides flexibility and a rational approach to drug development. Recent work has shown that antisense technology has the potential to address the antibiotic-resistance crisis, since resistance mechanisms for standard antibiotics apparently have no effect on antisense antimicrobials. Here, we describe current reports of antisense antimicrobials targeted against viruses, parasites, and bacteria. PMID- 27375109 TI - Antimicrobial Activity of Sebocytes against Propionibacterium acnes via Toll-Like Receptor 2 and Lysosomal Pathway. PMID- 27375110 TI - Genotype, Clinical Course, and Therapeutic Decision Making in 76 Infants with Severe Generalized Junctional Epidermolysis Bullosa. AB - Severe generalized junctional epidermolysis bullosa, a lethal hereditary blistering disorder, is usually treated by palliative care. Allogeneic stem cell transplantation (SCT) has been proposed as a therapeutic approach, yet without clinical evidence. Decision making was evaluated retrospectively in 76 patients with severe generalized junctional epidermolysis bullosa born in the years 2000 2015. The diagnosis was based on the absence of laminin-332 in skin biopsies. With an incidence of 1 of 150,000, severe generalized junctional epidermolysis bullosa occurred more often than published previously. Eleven as yet unreported mutations in the laminin-332 genes were detected. Although patients homozygous for the LAMB3 mutation c.1903C>T lived longer than the others, life expectancy was greatly diminished (10.8 vs. 4.6 months). Most patients failed to thrive. In two patients with initially normal weight gain, the decision for SCT from haploidentical bone marrow or peripheral blood was made. Despite transiently increasing skin erosions, the clinical status of both subjects stabilized for several weeks after SCT, but finally deteriorated. Graft cells, but no laminin 332, were detected in skin biopsies. The patients died 96 and 129 days after SCT, respectively, one of them after receiving additional skin grafts. Treatment of severe generalized junctional epidermolysis bullosa by SCT is a last-ditch attempt still lacking proof of efficacy. PMID- 27375111 TI - TGFbeta Induces a SAMHD1-Independent Post-Entry Restriction to HIV-1 Infection of Human Epithelial Langerhans Cells. AB - Sterile alpha motif (SAM) and histidine-aspartic (HD) domains protein 1 (SAMHD1) was previously identified as a critical post-entry restriction factor to HIV-1 infection in myeloid dendritic cells. Here we show that SAMHD1 is also expressed in epidermis-isolated Langerhans cells (LC), but degradation of SAMHD1 does not rescue HIV-1 or vesicular stomatitis virus G-pseudotyped lentivectors infection in LC. Strikingly, using Langerhans cells model systems (mutz-3-derived LC, monocyte-derived LC [MDLC], and freshly isolated epidermal LC), we characterize previously unreported post-entry restriction activity to HIV-1 in these cells, which acts at HIV-1 reverse transcription, but remains independent of restriction factors SAMHD1 and myxovirus resistance 2 (MX2). We demonstrate that transforming growth factor-beta signaling confers this potent HIV-1 restriction in MDLC during their differentiation and blocking of mothers against decapentaplegic homolog 2 (SMAD2) signaling in MDLC restores cells' infectivity. Interestingly, maturation of MDLC with a toll-like receptor 2 agonist or transforming growth factor-alpha significantly increases cells' susceptibility to HIV-1 infection, which may explain why HIV-1 acquisition is increased during coinfection with sexually transmitted infections. In conclusion, we report a SAMHD1-independent post-entry restriction in MDLC and LC isolated from epidermis, which inhibits HIV-1 replication. A better understanding of HIV-1 restriction and propagation from LC to CD4(+) T cells may help in the development of new microbicides or vaccines to curb HIV-1 infection at its earliest stages during mucosal transmission. PMID- 27375112 TI - Antagonistic Regulation of Intercellular Cohesion by Plakophilins 1 and 3. AB - Desmosomes are cell-cell adhesive structures essential for tissue integrity of the epidermis and the heart. Their constituents belong to multigene families giving rise to desmosomes of variable composition. So far, the functional significance of context-dependent composition in desmosome formation, dynamics, or stability during epidermal differentiation is incompletely understood. In this comparative study, we have uncovered unique and partially antagonistic functions of plakophilins 1 and 3 that are both expressed in the murine epidermis. These plakophilins differ in their localization patterns and kinetics during de novo desmosome formation and are regulated by distinct mechanisms. Moreover, plakophilin 3-containing desmosomes are more dynamic than desmosomes that contain predominantly plakophilin 1. Further, we show that Ca(2+)-independence of desmosomes strictly depends on plakophilin 1, whereas elevated levels of plakophilin 3 prevent the formation of hyperadhesive desmosomes in a protein kinase C alpha-dependent manner, even in the presence of plakophilin 1. Our study demonstrates that the balance between plakophilins 1 and 3 determines the context dependent properties of epidermal desmosomes. In this setting, plakophilin 1 provides stable intercellular cohesion that resists mechanical stress, whereas plakophilin 3 confers dynamics as required during tissue homeostasis and repair. Our data have implications for the role of plakophilins in carcinogenesis. PMID- 27375113 TI - Molecular epidemiology of GI and GII noroviruses in sewage: 1-year surveillance in eastern China. AB - AIMS: To determine the concentration and molecular epidemiology of GI and GII noroviruses in sewage in China. METHODS AND RESULTS: Twenty-three raw sewage samples were collected in the cities of Jinan and Linyi, eastern China in 2014. GI and GII noroviruses were positive in all samples after TaqMan-based quantitative PCR. The mean concentrations of GI and GII noroviruses were 4.52 * 10(4) and 7.88 * 10(4) genome copies per litre respectively. After reverse transcription-PCR, cloning and sequencing, 16 genotypes were identified. GI.6 (69.6%), GI.2 (65.2%), GII.13 (65.2%), GII.6 (60.9%) and GII.17 (60.9%) were the most common GI and GII genotypes. A recombination event was observed in two GI.6 sequences. GII.4 sequences belonged to Sydney 2012 and Den Haag 2006b variant. Interestingly, the novel GII.17 Kawasaki308 variant was detected. CONCLUSIONS: These results reveal that multiple norovirus genotypes cocirculated in the local population. The risk of acute gastroenteritis outbreak is high in the two cities due to the detection of GII.17 Kawasaki308 variant and the high concentration of norovirus in raw sewage. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates sewage surveillance can be a useful approach to monitor norovirus circulating in the population. PMID- 27375114 TI - Adverse Birth Outcomes And Oral Health. PMID- 27375116 TI - Light-Harvesting Nanotubes Formed by Supramolecular Assembly of Aromatic Oligophosphates. AB - A 2,7-disubstituted phosphodiester-linked phenanthrene trimer forms tubular structures in aqueous media. Chromophores are arranged in H-aggregates. Incorporation of small quantities of pyrene results in the development of light harvesting nanotubes in which phenanthrenes act as antenna chromophores and pyrenes as energy acceptors. Energy collection is most efficient after excitation at the phenanthrene H-band. Fluorescence quantum yields up to 23 % are reached in pyrene doped, supramolecular nanotubes. PMID- 27375115 TI - Mutational Spectrum of MYO15A and the Molecular Mechanisms of DFNB3 Human Deafness. AB - Deafness in humans is a common neurosensory disorder and is genetically heterogeneous. Across diverse ethnic groups, mutations of MYO15A at the DFNB3 locus appear to be the third or fourth most common cause of autosomal-recessive, nonsyndromic deafness. In 49 of the 67 exons of MYO15A, there are currently 192 recessive mutations identified, including 14 novel mutations reported here. These mutations are distributed uniformly across MYO15A with one enigmatic exception; the alternatively spliced giant exon 2, encoding 1,233 residues, has 17 truncating mutations but no convincing deafness-causing missense mutations. MYO15A encodes three distinct isoform classes, one of which is 395 kDa (3,530 residues), the largest member of the myosin superfamily of molecular motors. Studies of Myo15 mouse models that recapitulate DFNB3 revealed two different pathogenic mechanisms of hearing loss. In the inner ear, myosin 15 is necessary both for the development and the long-term maintenance of stereocilia, mechanosensory sound-transducing organelles that extend from the apical surface of hair cells. The goal of this Mutation Update is to provide a comprehensive review of mutations and functions of MYO15A. PMID- 27375117 TI - Harnessing solid-state packing for selective detection of chloride in a macrocyclic anionophore. AB - We report the synthesis of an inherently fluorescent macrocyclic receptor for chloride. The use of a disulphide tether provides for an excellent yield in the macrocyclization step. This compound binds chloride in the solution and solid state, and while unstable over time in aqueous solution, shows a selective response toward chloride over other anions in the solid state due to intermolecular interactions between fluorophore backbones. Surprisingly, the optoelectronic response to anions differs in solution and the films, with a distinct colorimetric response observed only in the film. PMID- 27375118 TI - Mycobacterium lutetiense sp. nov., Mycobacterium montmartrense sp. nov. and Mycobacterium arcueilense sp. nov., members of a novel group of non-pigmented rapidly growing mycobacteria recovered from a water distribution system. AB - From our recent survey of non-pigmented rapidly growing mycobacteria in the Parisian water system, three groups of isolates (taxons 1-3) corresponding to possible novel species were selected for taxonomic study. The three taxa each formed creamy white, rough colonies, had an optimal growth temperature of 30 degrees C, hydrolyzed Tween 80, were catalase-positive at 22 degrees C and expressed arylsulfatase activity. All three were susceptible to amikacin, ciprofloxacin and tigecycline. The three taxa produced specific sets of mycolic acids, including one family that has never previously been described, as determined by thin layer chromatography and nuclear magnetic resonance. The partial rpoB sequences (723 bp) showed 4-6 % divergence from each other and more than 5 % differences from the most similar species. Partial 16S rRNA gene sequences showed 99 % identity within each species. The most similar sequences for 16S rRNA genes (98-99 % identity over 1444-1461 bp) were found in the Mycobacterium fortuitum group, Mycobacterium septicum and Mycobacterium farcinogenes. The three taxa formed a new clade (bootstrap value, 99 %) on trees reconstructed from concatenated partial 16S rRNA, hsp65 and rpoB sequences. The above results led us to propose three novel species for the three groups of isolates, namely Mycobacterium lutetiense sp. nov. [type strain 071T=ParisRGMnew_1T (CIP 110656T=DSM 46713T)], Mycobacterium montmartrense sp. nov. [type strain 196T=ParisRGMnew_2T (CIP 110655T=DSM 46714T)] and Mycobacteriu marcueilense sp. nov. [type strain of 269T=ParisRGMnew_3T (CIP 110654T=DSM 46715T)]. PMID- 27375119 TI - Morphology and Molecular Phylogeny of Two Poorly Known Species of Protocruzia (Ciliophora: Protocruziida). AB - The ciliate genus Protocruzia is a highly confused group, which was formerly placed in the class Heterotrichea or Karyorelictea, and is according to the most recent system tentatively assigned to the class Spirotrichea. In the present study, the morphology, ciliary pattern, and molecular phylogeny of two poorly known species, Protocruzia tuzeti Villeneuve-Brachon, 1940, and Protocruzia granulosa Kahl, 1933, isolated from coastal waters of China, were investigated. Protocruzia tuzeti differs from its congeners mainly in possessing 6 adoral membranelles, 8-11 somatic kineties, and postoral dikinetids. Protocruzia granulosa is characterized by its extremely slender body, three postoral kineties, and 13 or 14 somatic kineties. The morphogenesis of P. granulosa is similar to that of P. tuzeti, especially in the parakinetal mode of stomatogenesis and the reorganization of the parental paroral membrane; however, more than one somatic kinety joins in the formation of the oral primordium in P. granulosa. Phylogenetic analyses based on small subunit ribosomal RNA gene revealed that six Protocruzia species form a fully supported clade that does not belong to any ciliate class; therefore, our data support the establishment of the class Protocruziea Gao et al. (Sci. Rep., 6, 2016, 24874). PMID- 27375120 TI - Partially ordered state of ice XV. AB - Most ice polymorphs have order-disorder "pairs" in terms of hydrogen positions, which contributes to the rich variety of ice polymorphs; in fact, three recently discovered polymorphs- ices XIII, XIV, and XV-are ordered counter forms to already identified disordered phases. Despite the considerable effort to understand order-disorder transition in ice crystals, there is an inconsistency among the various experiments and calculations for ice XV, the ordered counter form of ice VI, i.e., neutron diffraction observations suggest antiferroelectrically ordered structures, which disagree with dielectric measurement and theoretical studies, implying ferroelectrically ordered structures. Here we investigate in-situ neutron diffraction measurements and density functional theory calculations to revisit the structure and stability of ice XV. We find that none of the completely ordered configurations are particular favored; instead, partially ordered states are established as a mixture of ordered domains in disordered ice VI. This scenario in which several kinds of ordered configuration coexist dispels the contradictions in previous studies. It means that the order-disorder pairs in ice polymorphs are not one-to-one correspondent pairs but rather have one-to-n correspondence, where there are n possible configurations at finite temperature. PMID- 27375121 TI - Nanoscale imaging of untreated mammalian cells in a medium with low radiation damage using scanning electron-assisted dielectric microscopy. AB - Imaging of untreated living cells in a medium at a nanometre-scale resolution under physiological conditions is a significant challenge. Scanning electron microscopy (SEM) is widely used to observe cells in various atmospheric holders or special equipment. However, untreated biological specimens in aqueous solution generally incur heavy radiation damage from the direct electron beam (EB); and these images exhibit very poor contrast. Therefore, a new method for generating high-contrast images of living cells under physiological conditions without radiation damage has been strongly desired. Here, we demonstrate the first nanoscale observation of living cultured mammalian cells using our newly developed scanning-electron assisted dielectric microscopy (SE-ADM) method with a culture dish holder. Using the difference in relative permittivity between water and specimens, our SE-ADM system aids in the visualisation of untreated biological samples in aqueous solution. In addition, specimens incurred only a low level of radiation damage because the tungsten (W)-coated silicon nitride (SiN) film absorbs irradiated electrons. Untreated cells and organelles are clearly visible in high-contrast and high-resolution images without staining and fixation. Furthermore, our method enables the detection of changes in organelle structures within cells via time-lapse imaging with minimal radiation damage. PMID- 27375122 TI - Hematopoietic Cell Transplantation for Richter Syndrome. AB - Treatment combining chemotherapy with immunotherapy as well as novel targeted therapies have shown limited efficacy in Richter syndrome. Overall response rates after chemoimmunotherapy range from 43% to 67%, but remissions are generally short-lived. In chronic lymphocytic leukemia (CLL), allogeneic hematopoietic cell transplantation (all-HCT) is considered a potentially curative treatment modality, yielding 3-year overall survival rates exceeding 50% and a plateau in survival curves. In Richter syndrome, efficacy of allo-HCT depends on demonstrating an objective response (complete remission or partial response) before allografting, with resulting 3-year survival rates of 41% to 75%. On the other hand, the efficacy of autologous HCT is limited, especially when considering that patients autografted for Richter syndrome might relapse with CLL in 35% of cases. Notwithstanding the scarcity of published data, we recommend that patients with Richter syndrome should be referred to transplant centers as soon as the diagnosis is confirmed to evaluate their candidacy for allo-HCT. Establishing a clonal relationship to CLL is important considering the more aggressive disease course in clonally related Richter syndrome. Moreover, achievement of a complete remission or partial response to salvage therapy must be a prerequisite before moving forward with allografting for Richter syndrome. Patients who fail to demonstrate an objective response to salvage therapy should be considered for enrollment in clinical trials. PMID- 27375123 TI - Refining the Role of Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia as Novel Therapies Emerge. AB - Acute lymphoblastic leukemia (ALL) is a rare adult neoplasm. The disorder consists of precursor B or T phenotypes. In the pediatric population, ALL was a success story in that 80% of children with ALL enjoy long-term survival. In adults, similar complete remission rates are achieved with current induction regimens; however, less than 50% of patients are alive at 5 years, with most deaths due to relapsed disease. Accordingly, optimizing post remission consolidation therapy might improve in outcomes. Such strategies may include chemotherapy and autologous or allogeneic transplant. Moreover, the ability to modify such therapy based on better disease risk stratification while taking into account patient characteristics such as performance status and presence of comorbidities is necessary to tailor treatment accordingly. Here, we review available medical literature on the use of hematopoietic cell transplantation as a consolidation modality in the treatment of adult ALL. PMID- 27375124 TI - T Cell-Replete HLA Haploidentical Donor Transplantation with Post-Transplant Cyclophosphamide Is an Effective Salvage for Patients Relapsing after an HLA Matched Related or Matched Unrelated Donor Transplantation. AB - A second allogeneic hematopoietic stem cell transplantation (HSCT) using the same donor or another fully matched donor is an effective treatment approach for a subset of patients relapsing after a matched related (MRDT) or matched unrelated donor transplant (MUDT). There are limited data on the use of haploidentical transplantation (HIDT) with post-transplant cyclophosphamide in the setting of a second HSCT after an MRDT or MUDT. We analyzed the outcomes of 20 patients who received HIDT with post-transplant cyclophosphamide as a second HSCT after an MRDT (n = 10) or MUDT (n = 10). The median time from the first to the second HSCT was 20.7 months (range, 2.7 to 65.8). Ten patients had acute myelogenous leukemia/myelodysplastic syndrome, 6 had acute lymphoblastic leukemia, 2 had chronic lymphoblastic leukemia, and 2 had myeloproliferative neoplasms. All patients received cytoreductive therapy before HIDT, with 12 (60%) achieving complete remission and 8 (40%) with active disease at the time of transplant. All patients achieved sustained engraftment with median times to neutrophil and platelet engraftment of 17.5 days (range, 14 to 44) and 32 days (range, 15 to 99), respectively. Nineteen patients (95%) achieved full donor chimerism in both the T cell and myeloid lineages at day 30 post-HSCT. The cumulative incidences of grades II to IV and grades III to IV acute graft-versus-host disease at 180 days were 36% and 10%, respectively. The cumulative incidence of moderate to severe chronic graft-versus-host disease was 13% at 1 year post-HIDT. At a median follow up of 38 months, the probability of overall survival, disease-free survival, nonrelapse mortality, and relapse post-HIDT were 52%, 39%, 29%, and 33% at 1 year and 34%, 31%, 29%, and 40% at 3 years, respectively. These data suggest that HIDT is an effective strategy to treat relapsed hematologic malignancies after MRDT or MUDT. Further studies to confirm these observations are warranted. PMID- 27375125 TI - Cone-beam computed tomography of the orbit and optic canal volumes. AB - PURPOSE: The aim of this study was to measure orbital and optic canal volumes by means of cone-beam computed tomography (CBCT) of human skulls as a prerequisite for estimating alterations of this bony region by this method. MATERIALS AND METHODS: A total of 200 orbits of 100 adult individuals were investigated. These patients had no history of orbital trauma, dysplasia, or other diseases with a putative effect on orbital growth (female/male = 50/50; age: 20-70 years). Each 10 individuals with a male-to-female ratio of 1:1 constituted a 10-year age group. Area measurements and calculations of volumes were performed with OsiriX software. RESULTS: Orbital mean volume values did not differ significantly with respect to site. However, orbital volume slightly increased with age, whereas the optic canal volume declined over time. Mean orbital and optic canal volumes were larger in males than in females. Volumetric measurements of the orbit are in line with published data derived from computed tomograms and magnetic resonance images. CONCLUSION: Orbital and optical canal volumes in adults show sexual dimorphism and alter depending on age. CBCT is suitable for determining orbital volumes and the provided data can be useful, for example, for defining orbital pathologies, to calculate orbital reconstructions, or for use in anthropological studies. PMID- 27375126 TI - HIV-related stigma and universal testing and treatment for HIV prevention and care: design of an implementation science evaluation nested in the HPTN 071 (PopART) cluster-randomized trial in Zambia and South Africa. AB - BACKGROUND: Stigma and discrimination related to HIV and key populations at high risk of HIV have the potential to impede the implementation of effective HIV prevention and treatment programmes at scale. Studies measuring the impact of stigma on these programmes are rare. We are conducting an implementation science study of HIV-related stigma in communities and health settings within a large, pragmatic cluster-randomized trial of a universal testing and treatment intervention for HIV prevention in Zambia and South Africa and will assess how stigma affects, and is affected by, implementation of this intervention. METHODS/DESIGN: A mixed-method evaluation will be nested within HIV prevention trials network (HPTN) 071/PopART (Clinical Trials registration number NCT01900977), a three-arm trial comparing universal door-to-door delivery of HIV testing and referral to prevention and treatment services, accompanied by either an immediate offer of anti-retroviral treatment to people living with HIV regardless of clinical status, or an offer of treatment in-line with national guidelines, with a standard-of-care control arm. The primary outcome of HPTN 071/PopART is HIV incidence measured among a cohort of 52 500 individuals in 21 study clusters. Our evaluation will include integrated quantitative and qualitative data collection and analysis in all trial sites. We will collect quantitative data on indicators of HIV-related stigma over 3 years from large probability samples of community members, health workers and people living with HIV. We will collect qualitative data, including in-depth interviews and observations from members of these same groups sampled purposively. In analysis, we will: (1) compare HIV-related stigma measures between study arms, (2) link data on stigma to measures of the success of implementation of the PopART intervention and (3) explore changes in the dominant drivers and manifestations of stigma in study communities and the health system. DISCUSSION: HIV-related stigma may impede the successful implementation of HIV prevention and treatment programmes. Using a novel study-design nested within a large, community randomized trial we will evaluate the extent to which HIV-related stigma affects and is affected by the implementation of a comprehensive combination HIV prevention intervention including a universal test and treatment approach. PMID- 27375127 TI - Financing institutional long-term care for the elderly in China: a policy evaluation of new models. AB - A rapid ageing population coupled with changes in family structure has brought about profound implications to social policy in China. Although the past decade has seen a steady increase in public funding to long-term care (LTC), the narrow financing base and vast population have created significant unmet demand, calling for reforms in financing. This paper focuses on the financing of institutional LTC care by examining new models that have emerged from local policy experiments against two policy goals: equity and efficiency. Three emerging models are explored: Social Health Insurance (SHI) in Shanghai, LTC Nursing Insurance (LTCNI) in Qingdao and a means-tested model in Nanjing. A focused systematic narrative review of academic and grey literature is conducted to identify and assess these models, supplemented with qualitative interviews with government officials from relevant departments, care home staff and service users. This paper argues that, although SHI appears to be a convenient solution to fund LTC, this model has led to systematic bias in affordable access among participants of different insurance schemes, and has created a powerful incentive for the over provision of unnecessary services. The means-tested method has been remarkably constrained by narrow eligibility and insufficiency of funding resources. The LTCNI model is by far the most desirable policy option among the three studied here, but the narrow definition of eligibility has substantively excluded a large proportion of elders in need from access to care, which needs to be addressed in future reforms. This paper proposes three lines of LTC financing reforms for policy-makers: (1) the establishment of a prepaid financing mechanism pooled specifically for LTC costs; (2) the incorporation of more stringent eligibility rules and needs assessment; and (3) reforming the dominant fee-for-service methods in paying LTC service providers. PMID- 27375128 TI - Health provider responsiveness to social accountability initiatives in low- and middle-income countries: a realist review. AB - Social accountability in the health sector has been promoted as a strategy to improve the quality and performance of health providers in low- and middle-income countries. Whether improvements occur, however, depends on the willingness and ability of health providers to respond to societal pressure for better care. This article uses a realist approach to review cases of collective citizen action and advocacy with the aim to identify key mechanisms of provider responsiveness. Purposeful searches for cases were combined with a systematic search in four databases. To be included in the review, the initiatives needed to describe at least one outcome at the level of frontline service provision. Some 37 social accountability initiatives in 15 countries met these criteria. Using a realist approach, retroductive analysis and triangulation of methods and sources were performed to construct Context-Mechanism-Outcome configurations that explain potential pathways to provider responsiveness. The findings suggest that health provider receptivity to citizens' demands for better health care is mediated by health providers' perceptions of the legitimacy of citizen groups and by the extent to which citizen groups provide personal and professional support to health providers. Some citizen groups activated political or formal bureaucratic accountability channels but the effect on provider responsiveness of such strategies was more mixed. Favourable contexts for health provider responsiveness comprise socio-political contexts in which providers self-identify as activists, health system contexts in which health providers depend on citizens' expertise and capacities, and health system contexts where providers have the self perceived ability to change the system in which they operate. Rather than providing recipes for successful social accountability initiatives, the synthesis proposes a programme theory that can support reflections on the theories of change underpinning social accountability initiatives and interventions to improve the quality of primary health care in different settings. PMID- 27375130 TI - Ni exposure impacts the pool of free Fe and modifies DNA supercoiling via metal induced oxidative stress in Escherichia coli K-12. AB - The biology of nickel has been widely studied in mammals because of its carcinogenic properties, whereas few studies have been performed in microorganisms. In the present work, changes accompanying stress caused by nickel were evaluated at the cellular level using RNA-Seq in Escherichia coli K-12. Interestingly, a very large number of genes were found to be deregulated by Ni stress. Iron and oxidative stress homeostasis maintenance were among the most highly enriched functional categories, and genes involved in periplasmic copper efflux were among the most highly upregulated. These results suggest that the deregulation of Fe and Cu homeostatic genes is caused by a release of free Cu and Fe ions in the cell which in turn activate the Cu and Fe homeostatic systems. The content of Cu was not significantly affected upon the addition of Ni to the growth medium, nor were the Cus and CopA Cu-efflux systems important for the survival of bacteria under Ni stress In contrast the addition of Ni slightly decreased the amount of cellular Fe and activated the transcription of Fur regulated genes in a Fur-dependent manner. Cu or Fe imbalance together with oxidative stress might affect the structure of DNA. Further experiments revealed that Ni alters the state of DNA folding by causing a relaxed conformation, a phenomenon that is reversible by addition of the antioxidant Tiron or the Fe chelator Dip. The Tiron-reversible DNA relaxation was also observed for Fe and to a lesser extent with Cu but not with Co. DNA supercoiling is well recognized as an integral aspect of gene regulation. Moreover our results show that Ni modifies the expression of several nucleoid-associated proteins (NAPs), important agents of DNA topology and global gene regulation. This is the first report describing the impact of metal-induced oxidative on global regulatory networks. PMID- 27375131 TI - Diagnosis of Van den Ende-Gupta syndrome: Approach to the Marden-Walker-like spectrum of disorders. AB - Marden-Walker syndrome is challenging to diagnose, as there is significant overlap with other multi-system congenital contracture syndromes including Beals congenital contractural arachnodactyly, D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome), Schwartz-Jampel syndrome, Freeman-Sheldon syndrome, Cerebro-oculo-facio-skeletal syndrome, and Van den Ende-Gupta syndrome. We discuss this differential diagnosis in the context of a boy from a consanguineous union with Van den Ende-Gupta syndrome, a diagnosis initially confused by the atypical presence of intellectual disability. SNP microarray and whole exome sequencing identified a homozygous frameshift mutation (p.L870V) in SCARF2 and predicted damaging mutations in several genes, most notably DGCR2 (p.P75L) and NCAM2 (p.S147G), both possible candidates for this child's intellectual disability. We review distinguishing features for each Marden-Walker like syndrome and propose a clinical algorithm for diagnosis among this spectrum of disorders. (c) 2016 Wiley Periodicals, Inc. PMID- 27375132 TI - Oxidation-Responsive and "Clickable" Poly(ethylene glycol) via Copolymerization of 2-(Methylthio)ethyl Glycidyl Ether. AB - Poly(ethylene glycol) (PEG) is a widely used biocompatible polymer. We describe a novel epoxide monomer with methyl-thioether moiety, 2-(methylthio)ethyl glycidyl ether (MTEGE), which enables the synthesis of well-defined thioether-functional poly(ethylene glycol). Random and block mPEG-b-PMTEGE copolymers (Mw/Mn = 1.05 1.17) were obtained via anionic ring opening polymerization (AROP) with molecular weights ranging from 5 600 to 12 000 g.mol(-1). The statistical copolymerization of MTEGE with ethylene oxide results in a random microstructure (rEO = 0.92 +/- 0.02 and rMTEG E = 1.06 +/- 0.02), which was confirmed by in situ (1)H NMR kinetic studies. The random copolymers are thermoresponsive in aqueous solution, with a wide range of tunable transition temperatures of 88 to 28 degrees C. In contrast, mPEG-b-PMTEGE block copolymers formed well-defined micelles (Rh ~ 9-15 nm) in water, studied by detailed light scattering (DLS and SLS). Intriguingly, the thioether moieties of MTEGE can be selectively oxidized into sulfoxide units, leading to full disassembly of the micelles, as confirmed by detection of pure unimers (DLS and SLS). Oxidation-responsive release of encapsulated Nile Red demonstrates the potential of these micelles as redox-responsive nanocarriers. MTT assays showed only minor effects of the thioethers and their oxidized derivatives on the cellular metabolism of WEHI-164 and HEK-293T cell lines (1 1000 MUg.mL(-1)). Further, sulfonium PEG polyelectrolytes can be obtained via alkylation or alkoxylation of MTEGE, providing access to a large variety of functional groups at the charged sulfur atom. PMID- 27375133 TI - Decreased neural response for facial emotion processing in subjects with high genetic load for schizophrenia. AB - BACKGROUND: Patients with schizophrenia show impairment in facial emotion processing which is essential for successful social cognition. Using a functional magnetic resonance imaging (fMRI), this study aimed to investigate the implicit facial emotion recognition processing in participants with high genetic load for schizophrenia (GHR) as a possible trait marker of developing schizophrenia. METHODS: Block design fMRI of implicit facial emotion processing was used in 20 participants with GHR aged 16-35, and 17 age, sex, and education year-matched healthy controls (HC). During the facial emotional processing for fearful, happy, and neutral face stimuli, participants were asked to explicitly determine the gender per stimuli. RESULTS: Occipito-temporo-limbic area in fearful face condition and involvement of broader region including prefrontal cortex in neutral face condition revealed significant attenuation of BOLD signal activation in GHR compared to HC. The GHR demonstrated less activity in right amygdala during fearful and neutral face condition. CONCLUSION: The study presented that GHR displayed abnormal brain activity in occipito-temporo-limbic-frontal network implicated in facial emotion processing. It indicates that abnormal facial emotion processing may be influenced by a genetic factor and could be a trait marker in schizophrenia. PMID- 27375134 TI - The gamma-glutamyl transpeptidase-to-platelet ratio predicts liver fibrosis and cirrhosis in HBeAg-positive chronic HBV infection patients with high HBV DNA and normal or mildly elevated alanine transaminase levels in China. AB - The gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is a new serum diagnostic model, which is reported to be more accurate than aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on the four factors (Fib-4) for the diagnosis of significant fibrosis and cirrhosis in chronic HBV infection (CHBVI) patients in West Africa. To evaluate the performance of the GPR model for the diagnosis of liver fibrosis and cirrhosis in HBeAg-positive CHBVI patients with high HBV DNA (>=5 log10 copies/mL) and normal or mildly elevated alanine transaminase (ALT) (<=2 times upper limit of normal (ULN)) in China. A total of 1521 consecutive CHBVI patients who underwent liver biopsies and routine laboratory tests were retrospectively screened. Of these patients, 401 treatment naive HBeAg-positive patients with HBV DNA>=5 log10 copies/mL and ALT<=2 ULN were included. The METAVIR scoring system was adopted as the pathological diagnosis standard of liver fibrosis. Using liver histology as a gold standard, the performances of GPR, APRI, and Fib-4 for the diagnosis of liver fibrosis and cirrhosis were evaluated and compared by receiver operating characteristic (ROC) curves and the area under the ROC curves (AUROCs). Of 401 patients, 121 (30.2%), 49 (12.2%) and 17 (4.2%) were classified as having significant fibrosis (>=F2), severe fibrosis (>=F3) and cirrhosis (=F4), respectively. After estimating the AUROC to predict significant fibrosis, the performance of GPR (AUROC=0.66, 95% CI 0.60-0.72) was higher than APRI (AUROC=0.58, 95% CI 0.52-0.64, P=.002) and Fib-4 scores (AUROC=0.54, 95% CI 0.47 0.60, P<.001). After estimating the AUROC to predict severe fibrosis, the performance of GPR (AUROC=0.71, 95% CI 0.63-0.80) was also higher than APRI (AUROC=0.65, 95% CI 0.56-0.73, P=.003) and Fib-4 scores (AUROC=0.67, 95% CI 0.58 0.75, P=.001). After estimating the AUROC to predict cirrhosis, the performance of GPR (AUROC=0.73, 95% CI 0.56-0.88) was higher than APRI (AUROC=0.69, 95% CI 0.54-0.83, P=.041) and Fib-4 scores (AUROC=0.69, 95% CI 0.55-0.82, P=.012) too. The GPR is a new serum model for the diagnosis of liver fibrosis and cirrhosis and shows obvious advantages in Chinese HBeAg-positive patients with HBV DNA>=5 log10 copies/mL and ALT<=2 ULN compared with APRI and Fib-4, thus warranting its widespread use for this specific population. PMID- 27375135 TI - Evaluation of simple blood counts as inflammation markers for brain tumor patients. AB - AIMS: Hemogram parameters in routine blood panels have been proposed as inflammation markers. These parameters, especially the red cell distribution width (RDW) and mean platelet volume (MPV), were evaluated as surrogate inflammatory markers in brain tumor patients. We aimed to observe RDW and MPV values of tumor patients and compare to those in healthy population. METHODS: We recorded white blood cell count, neutrophil count, lymphocyte count, hemoglobin, hematocrit, RDW, platelet count, and MPV of the study group at the time of diagnosis and compared to those of the control subjects. RESULTS: The RDW was significantly elevated in study group compared to that of the control subjects (p=0.001). The MPV was significantly lower in study group than that of the control group (p=0.01). CONCLUSION: Decreased MPV and increased RDW were both associated with brain tumor. However, prospective studies with larger sample sizes are needed to support the results and expose MPV and RDW variations between metastatic and primary brain tumors. PMID- 27375136 TI - A challenging entity of unruptured giant saccular aneurysms of vertebrobasilar artery. AB - PURPOSE: Giant intracranial aneurysms commonly cause poor clinical outcome and few studies focus on them. This study is to retrospectively report the angiographic and clinical presentations in unruptured giant saccular vertebrobasilar aneurysms with and without endovascular treatment. METHODS: Out of 400 patients who had unruptured posterior circulation aneurysms in a single center, we found 10 unruptured giant (>25mm) saccular vertebrobasilar aneurysms. Clinical and angiographic presentations as well as their clinical outcomes were assessed. RESULTS: Of the 10 giant aneurysms in 10 patients, three were left untreated. During 6 months follow-up, all 3 of these patients died from aneurysm rupture. The remaining 7 patients were treated by endovascular procedure, 5 received stent-assisted coiling, 1 was treated by parent artery occlusion (PAO), and 1 was treated by conventional coiling. Of these treated patients, only one survived during a 22 month period of follow-up. CONCLUSIONS: Patients with giant saccular aneurysms of vertebrobasilar artery presenting mass effect may have extremely poor clinical outcomes and may not benefit from endovascular treatment. PMID- 27375137 TI - Comprehensive imaging of stroke - Looking for the gold standard. AB - BACKGROUND AND PURPOSE: Stroke is the third cause of death worldwide. In recent decade there has been a marked progress in treatment and prevention of stroke, which was possible largely due to modern neuroimaging techniques. Early radiological confirmation of the diagnosis allows for introduction of fibrinolytic therapy and evaluation of ischaemic penumbra. MATERIAL AND METHODS: We have analysed clinical and imaging data of 92 patients with early stages of stroke. The sensitivity, specificity and possible influence on the choice of treatment were assessed for different neuroimaging techniques, including diffusion weighted and perfusion imaging in patients with hyperacute and acute stroke. RESULTS: A non-contrast computed tomography (CT) allowed for the detection of early ischaemic changes with an overall sensitivity of 38% and 42% in patients in hyperacute phase. In a perfusion CT study the perfusion abnormalities in the area corresponding to the clinical symptoms were present in 79% of patients. The sensitivity of diffusion weighted imaging (DWI) alone was 95% and in conjunction with perfusion MR reached 100%. CONCLUSIONS: Our study proves that advanced neuroimaging modalities allow for a substantial increase of sensitivity when detecting changes in patients with acute ischaemic strokes and confirming the clinical diagnosis. We believe that MR in combination with DWI should be the imaging methods of choice in diagnosing acute stroke patients. Perfusion adds significant diagnostic value to structural techniques, particularly in clinically ambiguous cases. In cases with a clear clinical picture the data provided by a non-contrast CT study is sufficient for therapeutic decision making. PMID- 27375138 TI - Bone metabolism and vitamin D status in patients with multiple sclerosis. AB - BACKGROUND: Vitamin D (VD), an important factor for bone health immobilization and immune regulation, has been shown to have low serum concentration in multiple sclerosis (MS) patients. Those patients have also multiple fracture risk factors, including progressive immobilization and long-term glucocorticoids treatment. The aim of the study was to analyze bone health (osteopenia or osteoporosis prevalence) and VD serum concentration in MS patients as well as the influence of disease activity and treatment on bone health. MATERIALS AND METHODS: The study involved 72 MS patients: 52 women and 20 men. Mean age was 40.3+/-10.5 yrs, mean EDSS (Expanded Disability Status Scale) 3.3+/-1.9. Bone health was analyzed using standard densitometry in the lumbar spine and femoral neck. Serum levels of VD, calcium, phosphate and parathormone were assessed. We compared two groups of patients with multiple sclerosis: relapsing - remitting MS (RRMS) and progressive relapsing MS (PRMS). RESULTS: Densitometry revealed osteopenia in twenty-six (36.1%) patients and osteoporosis in eleven (15.3%), no bone fractures were presented. Sixty-eight MS patients (94.4%) had lower VD serum level if compared to population referential values. Thirteen patients (18.1%) had severe VD deficiency. Densitometry parameter (T-score of the lumbar spine) worsened with EDSS increase (r=-0.43, P=0.001). There was a statistically significant negative correlation between VD concentration and EDSS score (r=-0.31; P=0.009). CONCLUSIONS: Our study indicates that patients with MS have high incidence of osteopenia and osteoporosis and vitamin D deficiency. Bone health disturbances studied by densitometry are related to the disability caused by MS. PMID- 27375139 TI - Deep brain stimulation of the internal globus pallidus for disabling haloperidol induced tardive dystonia. Report of two cases. AB - AIM: Tardive dystonia (TD) represents a side effect of prolonged intake of neuroleptic drugs. TD can be a disabling movement disorder persisting despite available medical treatment. Deep brain stimulation (DBS) has been reported successful in this condition although the number of treated patients with TD is still limited to small clinical studies or case reports. In this study, we present 2 additional cases of patients after bilateral globus pallidus internus (GPi) stimulation. METHODS: The formal assessment included the Burke-Fahn Dystonia Rating Scale (BFMDRS). The preoperative and postoperative functional and motor parts of this scale were compared in each patient. The postoperative assessments were done every 6 months. RESULTS: Both patients underwent successful bilateral GPi DBS for TD. The postoperative motor score improved by 78% at 24 months in patient 1 and 69% at 12 months in patient 2. There were no surgical or hardware-related complications over follow-up period. CONCLUSION: Our experience indicates that bilateral GPi DBS can be an effective treatment for disabling TD. The response of TD to bilateral GPi DBS is very rapid and occurs within days after the procedure. PMID- 27375140 TI - Novel mutation of the NOTCH3 gene in a Polish family with CADASIL. AB - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small blood vessels disease caused by mutations in the gene encoding the neurogenic locus notch homolog protein 3 (NOTCH 3). We present a Polish family with a previously unreported novel mutation in exon 12 c.1851C>C/G of the NOTCH3 gene and varying disease expression. One of the two family members with the confirmed mutation presented with all the main CADASIL symptoms; while, his affected father was nearly asymptomatic. Both family members had epilepsy, coronary artery disease, and abdominal aorta aneurysm. Our observation confirms there is phenotypic variability in CADASIL not only between, but also within, families carrying the same mutation. PMID- 27375141 TI - The emotional stress and risk of ischemic stroke. AB - Stroke is the second leading cause of death worldwide, and the leading cause of acquired disability in adults in most regions. There have been distinguished modifiable and non-modifiable risk factors of stroke. Among them the emotional stress was presented as a risk factor. The aim of this review was to present available data regarding the influence of acute and chronic mental stress on the risk of ischemic stroke as well as discussing the potential pathomechanisms of such relationship. There is an evident association between both acute and chronic emotional stress and risk of stroke. Several potential mechanisms are discussed to be the cause. Stress can increase the cerebrovascular disease risk by modulating symphaticomimetic activity, affecting the blood pressure reactivity, cerebral endothelium, coagulation or heart rhythm. The emotional stress seems to be still underestimated risk factor in neurological practice and research. Further studies and analyses should be provided for better understanding of this complex, not fully known epidemiological problem. PMID- 27375142 TI - Cortical laminar necrosis following myocardial infarction. AB - The cortical laminar necrosis (CLN) is a permanent injury characterized by the selective delayed necrosis of the cerebral cortex, mainly of the third layer, and usually greater in the depths and sides of the sulci than over the crest of the gyri. The damage involves all cellular components - either neurons, glia cells and blood vessels - and results in a focal cortical band of pan-necrosis detectable in late sub-acute or chronic stages of reduced energy supply to the brain. The CLN has been described in different conditions as hypoxia, hypoglycemia and status epilepticus. At brain CT or MR scans it appears with pathognomonic highly hyperdense or T1-hyperintense lesions following the gyral anatomy of the cerebral cortex. We reported a case of CLN associated to myocardial infarct and discussed the underlying mechanisms. PMID- 27375143 TI - Simultaneous bilateral hypertensive basal ganglia hemorrhage. AB - CONTEXT: Hypertension is the single most important risk factor for intracerebral hemorrhage (ICH) and often leads to solitary hematoma. Multiple spontaneous simultaneous ICH is not common, and bilateral hemorrhages occurred in symmetrical basal ganglia is extremely rare. Most reported cases accepted conservative treatment and suffered extremely poor outcome. CASE REPORT: A 57-year-old male became unconscious when having supper and was transported to our emergency room immediately. Non-contract CT brain scanning showed simultaneous bilateral hypertensive basal ganglia hemorrhage; he was treated by stereotactic aspiration and thrombolysis for both sides, with subsequent thrombolysis and clot aspiration through hematoma-indwelling catheter. The hematomas were almost totally cleared within a week. His condition improved gradually. Nearly 10 months after onset, he could chow and swallow food, controlling bowels and bladder all by himself, but need some help when feeding and using toilet. CONCLUSION: Simultaneous bilateral hypertensive basal ganglia hemorrhage is a devastating cerebrovascular disease with significant high morbidity and mortality. Stereotactic aspiration and thrombolysis is a safe and effective way to clear hematomas within short time, thus reducing the neurological impairment from hematoma mass effect and secondary brain injury, improving prognosis. PMID- 27375144 TI - Acute infarction of corpus callosum due to transient obstructive hydrocephalus. AB - Acute ischemia of the corpus callosum (CC) is not a well-known feature in patients with acute hydrocephalus. Herein, we describe a case with acute CC infarction due to another rare entity; transient obstructive hydrocephalus. A 66 year-old male was admitted with sudden onset right-sided hemiparesia. CT demonstrated a hematoma on the left basal ganglia with extension to all ventricles. The following day, the patient's neurological status progressed to coma and developed bilateral pyramidal signs. MRI demonstrated obstructive hydrocephalus and acute diffuse infarction accompanied by elevation of the CC. On the same day there was improvement in his neurological status with significant decrease in ventricular size and complete resolution of the clot in the third ventricle. The mechanism of signal abnormalities is probably related with the neural compression of the CC against the falx. Presumably, the clot causing obstruction in the third ventricle dissolved or decayed by the help of fibrinolytic activity of CSF, which was raised after IVH and caused spontaneous improvement of hydrocephalus. Bilateral neurological symptoms suggest diffuse axonal damage and normalization of the intracranial pressure should be performed on the early onset of clinical detorioration in order to prevent axonal injury. PMID- 27375145 TI - Association of myasthenia gravis and Behcet's disease: A case report. AB - Myasthenia gravis is a disease of neuromuscular junction due to auto-immune destruction of the acetylcholine receptors. Behcet's disease, on the other hand, is a multisystemic vascular-inflammatory disease. Both conditions are not common in the general population although their association has not been reported in the literature. We wanted to present our patient who developed clinical course of myasthenia gravis following discontinuation of medications due to complications of corticosteroid for Behcet's disease. It was observed that clinical findings of myasthenia gravis recovered following restarting steroid treatment and he did not experience attacks of both conditions. Although Myasthenia gravis and Behcet's disease are distinct entities clinically as well as in terms of pathogenesis, they share common physiopathological features and their treatment is based on their common features. PMID- 27375146 TI - The molecular pattern of histopathological progression to anaplastic meningioma - A case report. AB - Meningiomas (MGs) are the most frequent primary tumours of the central nervous system (CNS) and exhibit a large spectrum of histological types and clinical phenotypes. The WHO classification of CNS tumours established strict diagnostic criteria of the benign (Grade 1), atypical (Grade 2) and anaplastic (Grade 3) subtypes. Combined with the resection rate, WHO grading has the most crucial role as the prognostic factor. Additionally, such biomarkers as Ki-67/MIB-1, progesterone receptors and phosphor-histone H3 were correlated with MG progression. Recently, it was suggested that the aggressive behaviour of some MGs is attributed to molecular alterations, regardless of their histopathology. The analysis of loss of heterozygosity (LOH) at chromosomes 1, 9, 10, 14 and 22 was performed. The presented case of WHO Grade 2 MG initially exhibited LOH at chromosomes 10, 14 and 22. In the first recurrence, the tumour genetic profiling revealed additional LOH at chromosome 1p and atypical histopathology. During the second recurrence, an aggressive phenotype was observed and tumour progressed to an anaplastic form. Considering the appearance of the tumour relapses, the set of molecular changes overtook the histopathological progression. The genetic and histopathological imbalance in the tumour progression in secondary anaplastic MGs has not been previously described. The evolution of genetic and histopathological changes was presented in the same patient. In the future, the individualised therapy of potentially more aggressive forms of MGs could be based on certain chromosome aberrations. PMID- 27375147 TI - Silent killer: A scalpel in the aortic wall after spinal surgery. AB - Iatrogenic vascular injury during lumbar spinal surgery is rare, but may lead to serious complications in unrecognized cases. Especially, injuries to aorta or its major branches may result in death unless diagnosed and treated immediately. We present a rare case of aortic injury with a scalpel in a 56-year-old male patient undergoing lumbar disk surgery. The vascular injury was successfully treated with open surgery. The post-operative period was uneventful and the patient was discharged in a healthy condition on the 8th day. This case once again reminds us that surgery is always open to complications and that early diagnosis and appropriate interventions are of paramount importance to overcome these complications. PMID- 27375148 TI - Osteolytic clear cell meningioma of the petrous bone occurring 36 years after posterior cranial fossa irradiation: Case report. AB - OBJECTIVE AND IMPORTANCE: While bone invasion and hyperostosis are frequent phenomena in meningiomas, primary intraosseous meningiomas are rare and their occurrence in the skull base is an extraordinary exception. Moreover, radiation induced meningiomas represent a unique clinical dilemma given the fact that patients with these tumors had often received a prior full course of radiotherapy. CLINICAL PRESENTATION: A 42-year-old man presented with a 3-month history of progressively worsening facial asymmetry. His medical history was consistent for a posterior cranial fossa irradiation at the age of 6 years for a non-confirmed brain stem tumor. On admission his Karnofsky performance status was graded as 50% and his neurological examination showed a complete right facial nerve paralysis and hearing impairment. Computed tomography and magnetic resonance imaging demonstrated an osteolytic tumor invading the whole right petrous bone without intracranial involvement. INTERVENTION: As the tumor reached the external auditory canal, a tissue sample was obtained locally. Pathological examination of the lesion identified a grade II clear cell meningioma and the patient was consequently addressed for an intensity modulated radiation therapy. His condition remained unchanged till the most recent follow-up examination, 8 months later. CONCLUSIONS: To the best of our knowledge, a radiation induced osteolytic clear cell meningioma of the petrous bone has not been previously reported. As little literature exists regarding the use of adjuvant therapies for these tumors, intensity modulated radiation therapy remains an attractive treatment option in case of pervious irradiation and general status alteration. PMID- 27375149 TI - Deep brain stimulation or thalamotomy in fragile X-associated tremor/ataxia syndrome? Case report. AB - We present the case of a 66-year-old man who has been treated for essential tremor since the age of 58. He developed mild cerebellar gait ataxia seven years after tremor onset. Moderate, global brain atrophy was identified on MRI scans. At the age of 68, only temporary tremor relief could be achieved by bilateral deep brain stimulation of the ventral intermedius nucleus of the thalamus. Bilateral stimulation of the subthalamic nucleus also resulted only in transient improvement. In the meantime, progressive gait ataxia and tetraataxia developed accompanied by other cerebellar symptoms, such as nystagmus and scanning speech. These correlated with progressive development of bilateral symmetric hyperintensity of the middle cerebellar peduncles on T2 weighted MRI scans. Genetic testing revealed premutation of the FMR1 gene, establishing the diagnosis of fragile X-associated tremor/ataxia syndrome. Although this is a rare disorder, it should be taken into consideration during preoperative evaluation of essential tremor. Postural tremor ceased two years later after thalamotomy on the left side, while kinetic tremor of the right hand also improved. PMID- 27375150 TI - Non-surgical treatment of massive traumatic corpus callosum hematoma after blunt head injury: A case report. AB - Massive hematoma of the corpus callosum caused by blunt head trauma is an extremely rare lesion. Most frequent traumatic lesions involve the corpus callosum are diffuse axonal injuries. They might be associated with small hemorrhagic foci in the hemispheric and brain stem white matter, intraventricular hemorrhages, subarachnoid hemorrhages, traumatic lesions of the septum pellucidum and fornix. Many cases of corpus callosum injury present with permanent disconnection syndrome. We present a case of a 32-year-old female suffered blunt head trauma resulted in massive corpus callosum hematoma which was managed non surgically. The patient initially had a reduced conscious level and symptoms of disconnection syndrome, and significant recovery was observed at 6 months follow up. PMID- 27375151 TI - Intravascular lymphoma mimicking multiple sclerosis. AB - Diagnosis of relapsing-remitting multiple sclerosis requires demonstration disseminated symptoms in time and space on the basis of neurological assessment or magnetic resonance imaging findings. In addition, the diagnosis is conditioned by ruling out other conditions that may explain the clinical symptoms. We describe the patient presenting in the initial stage of the disease neurological symptoms and magnetic resonance imaging lesions, that met criteria for relapsing remitting multiple sclerosis diagnosis. The patient was administered immunomodulatory treatment. However, the subsequent course of the disease tended to verify the diagnosis. Finally, the patient was diagnosed with intravascular B cell lymphoma. Intravascular lymphoma is a rare form of lymphoma characterized by the development of cancerous cells in the lumen of small and medium-sized blood vessels. Due to the lack of characteristic biomarkers in laboratory tests and neuroimaging, the diagnosis is based on histopathological examination of the sample of the affected organ taken by biopsy. It should be consider in all cases of central nervous system damage of unknown, undiagnosed etiology. PMID- 27375152 TI - Hyperdense artery sign in middle cerebral and basilar arteries: A catastrophic stroke. PMID- 27375153 TI - Corrigendum to "Evolution of diagnostic criteria for multiple sclerosis" [Pol. J. Neurol. Neurosurg. 49 (5) (2015) 313-321]. PMID- 27375154 TI - Outcomes of surgical repairs for thoracic aortic pseudoaneurysms after cardiovascular surgery. AB - AIM: A thoracic aortic pseudoaneurysm is a life-threatening complication after cardiovascular surgery. We reviewed the short- and long-term outcomes following the surgical repair of thoracic aortic pseudoaneurysms. METHODS: We reviewed 20 patients (mean age, 63.3 +/- 10.8 years) who underwent surgical repair for a thoracic aortic pseudoaneurysm after cardiovascular surgery over the past 17 years. The mean follow-up period was 5.7 +/- 4.2 years and the rate of follow-up was 90.0%. RESULTS: Ten patients were asymptomatic, and the remaining had preoperative symptoms (rupture, n = 4; dyspnea, n = 4; hemoptysis, n = 2; hoarseness, n = 1; chest pain, n = 1; anemia, n = 1; and jugular venous distension, n = 1). The interval between previous and present surgery was 14.9 +/ 8.0 years. Although aortic injury with massive bleeding occurred during re sternotomy, there were no hospital deaths, and all patients were discharged from our hospital. Late survival rates at 5 years and 10 years were 83.3% +/- 8.8% and 72.9% +/- 12.4%, respectively. There were five late deaths, and no aorta-related deaths. CONCLUSIONS: Outcomes of surgical repair of thoracic aortic pseudoaneurysms are satisfactory. However, even in asymptomatic patients, lifelong patient follow-up is required. PMID- 27375155 TI - Highly Fluorescent Nanotubes with Tunable Diameter and Wall Thickness Self Assembled from Asymmetric Perylene Diimides. AB - Highly fluorescent bilayer-walled and monolayer-walled nanotubes are assembled from elaborately designed asymmetric perylene diimide (PDI) molecules. The diameter of bilayer-walled nanotubes increases with the size of the branched substituents at the meta-position of the phenyl moiety of PDI molecules, whereas that of monolayer-walled nanotubes remains unchanged regardless of the size of branched substituents. PMID- 27375156 TI - Post-Transplantation Natural Killer Cell Count: A Predictor of Acute Graft-Versus Host Disease and Survival Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation. AB - BACKGROUND: Reconstitution of the immune system after allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays an important role in post-transplant outcomes. However, the clinical relevance of the lymphocyte subset (LST) counts to transplant-related complications and survival outcomes after allo-HSCT has not been fully elucidated. PATIENTS AND METHODS: A total of 70 patients who had undergone allo-HSCT from 2007 to 2013, with LST results both 7 days before conditioning and 30 or 90 days after allo-HSCT were included. The LST counts in the peripheral blood were determined using 6-color flow cytometry. Clinical information, including transplant-related events during the first 100 days after allo-HSCT, was reviewed, and any association between these events and LST was analyzed. RESULTS: At 30 days after allo-HSCT, the CD4+ T-cell (P = .009) and B cell (P = .035) counts were lower and the natural killer (NK) cell count was greater (P < .001) than before conditioning. The CD8+ T-cell (P = .001) and NK cell (P < .001) counts were high 90 days after transplantation. The hazard ratios for a low NK cell count on days 30 and 90 for acute graft-versus-host disease were 6.22 and 14.67, respectively. Patients with low NK cell counts at 30 and 90 days after allo-HSCT had poorer overall survival (P = .043 and P = .028, respectively) and greater nonrelapse mortality (P = .036 and P = .033, respectively). A low NK cell count on day 30 was still prognostic for overall survival (P = .039) on multivariable analysis. CONCLUSION: NK cell counts after allo-HSCT, especially on day 30, were predictive of acute graft-versus-host disease, nonrelapse mortality, and survival. Serial lymphocyte subset analysis can be used to identify and treat patients at risk during the early period after allo-HSCT. PMID- 27375157 TI - Survival of Secondary Central Nervous System Lymphoma Patients in the Rituximab Era. PMID- 27375159 TI - Anaplastic Multiple Myeloma: An Aggressive Variant With a Poor Response to Novel Therapies. PMID- 27375158 TI - Diffuse Large B-Cell Lymphoma in the Elderly: Real World Outcomes of Immunochemotherapy in Asian Population. AB - BACKGROUND: We evaluated the real-life treatment outcomes of elderly patients with diffuse large B-cell lymphoma from a homogenous Asian population and defined the cutoff age for "elderly." PATIENTS AND METHODS: The medical records of 192 DLBCL patients aged > 60 years who had received first-line immunochemotherapy were retrospectively evaluated. The treatment schedule, adverse events, and survival outcomes were analyzed overall and stratified by 4 age groups (> 60-64, 65-69, 70-74, and >= 75 years). RESULTS: Patient age of >= 75 years was associated with a significantly lower complete remission rate (86.5% vs. 81.4% vs. 82.0% vs. 51%; P < .001) and greater treatment-related mortality (5.4% vs. 9.3% vs. 13.1% vs. 33.3%; P = .001). Advanced age was also related to dose reductions (24.3% vs. 39.5% vs. 73.8% vs. 100%; P < .001) and a lower likelihood of completing the planned chemotherapy cycle (73% vs. 79.1% vs. 78.7% vs. 51%, P = .005). Significantly poorer progression-free survival (3-year rate, 73.5% vs. 61.5% vs. 65.2% vs. 38.3%; P < .001) and overall survival (3-year rate, 77.9% vs. 74.1% vs. 70.9% vs. 43.6%; P < .001) were observed for patients aged >= 75 years. Multivariate regression analyses identified age >= 75 years and initial Eastern Cooperative Oncology Group performance status as potential risk factors associated with overall survival. CONCLUSION: Elderly patients aged < 75 years were able to tolerate standard immunochemotherapy, with acceptable survival profiles. In an Asian population, 75 years seems to be a judicious cutoff for predicting treatment outcomes. PMID- 27375160 TI - Polymeric Cups for Cavitation-mediated Delivery of Oncolytic Vaccinia Virus. AB - Oncolytic viruses (OV) could become the most powerful and selective cancer therapies. However, the limited transport of OV into and throughout tumors following intravenous injection means their clinical administration is often restricted to direct intratumoral dosing. Application of physical stimuli, such as focused ultrasound, offers a means of achieving enhanced mass transport. In particular, shockwaves and microstreaming resulting from the instigation of an ultrasound-induced event known as inertial cavitation can propel OV hundreds of microns. We have recently developed a polymeric cup formulation which, when delivered intravenously, provides the nuclei for instigation of sustained inertial cavitation events within tumors. Here we report that exposure of tumors to focused ultrasound after intravenous coinjection of cups and oncolytic vaccinia virus , leads to substantial and significant increases in activity. When cavitation was instigated within SKOV-3 or HepG2 xenografts, reporter gene expression from vaccinia virus was enhanced 1,000-fold (P < 0.0001) or 10,000 fold (P < 0.001), respectively. Similar increases in the number of vaccinia virus genomes recovered from tumors were also observed. In survival studies, the application of cup mediated cavitation to a vaccinia virus expressing a prodrug converting enzyme provided significant (P < 0.05) retardation of tumor growth. This technology could improve the clinical utility of all biological therapeutics including OV. PMID- 27375162 TI - Interventions to reduce waiting times for elective procedures: a Cochrane review summary. PMID- 27375161 TI - ATRA modulates mechanical activation of TGF-beta by pancreatic stellate cells. AB - The hallmark of pancreatic ductal adenocarcinoma (PDAC) is abundant desmoplasia, which is orchestrated by pancreatic stellate cells (PSCs) and accounts for the majority of the stroma surrounding the tumour. Healthy PSCs are quiescent, but upon activation during disease progression, they adopt a myofibroblast contractile phenotype and secrete and concomitantly reorganise the stiff extracellular matrix (ECM). Transforming growth factor beta (TGF-beta) is a potent activator of PSCs, and its activation requires spatiotemporal organisation of cellular and extracellular cues to liberate it from an inactive complex with latent TGF-beta binding protein (LTBP). Here we study the mechanical activation of TGF-beta by PSCs in vitro by investigating LTBP-1 organisation with fibrillar fibronectin and show that all trans-retinoic acid (ATRA), which induces PSC quiescence, down-regulates the ability of PSCs to mechanically organise LTBP-1 and activate TGF-beta through a mechanism involving myosin II dependent contractility. Therefore, ATRA inhibits the ability of PSCs to mechanically release active TGF-beta, which might otherwise act in an autocrine manner to sustain PSCs in an active state and a tumour-favouring stiff microenvironment. PMID- 27375163 TI - When the patient must carry the communicative burden. PMID- 27375165 TI - Regioisomer-specific electron affinities and electronic structures of C70para adducts at polar and equatorial positions with (bromo)benzyl radicals: photoelectron spectroscopy and theoretical study. AB - Negative ion photoelectron spectroscopy shows interesting regioisomer-specific electron affinities (EAs) of 2,5- and 7,23-para-adducts of C70 [(ArCH2)2C70] (Ar = Ph, o-, m-, and p-BrC6H4). Their EA values are larger than that of C70 by 5-150 meV with the 2,5-polar adducts' EAs being higher than their corresponding 7,23 equatorial counterparts, exhibiting appreciable EA tunable ranges and regioisomeric specificity. Density functional theory (DFT) calculations reproduce both the experimental EA values and EA trends very well. PMID- 27375166 TI - Carbon-Ion Radiation Therapy for Pelvic Recurrence of Rectal Cancer. AB - PURPOSE: Investigation of the treatment potential of carbon-ion radiation therapy in pelvic recurrence of rectal cancer. METHODS AND MATERIALS: A phase 1/2 dose escalation study was performed. One hundred eighty patients (186 lesions) with locally recurrent rectal cancer were treated with carbon-ion radiation therapy (CIRT) (phase 1/2: 37 and 143 patients, respectively). The relapse locations were 71 in the presacral region, 82 in the pelvic sidewalls, 28 in the perineum, and 5 near the colorectal anastomosis. A 16-fraction in 4 weeks dose regimen was used, with total dose ranging from 67.2 to 73.6 Gy(RBE); RBE-weighted absorbed dose: 4.2 to 4.6 Gy(RBE)/fraction. RESULTS: During phase 1, the highest total dose, 73.6 Gy(RBE), resulted in no grade >3 acute reactions in the 13 patients treated at that dose. Dose escalation was halted at this level, and this dose was used for phase 2, with no other grade >3 acute reactions observed. At 5 years, the local control and survival rates at 73.6 Gy(RBE) were 88% (95% confidence interval [CI], 80%-93%) and 59% (95% CI, 50%-68%), respectively. CONCLUSION: Carbon-ion radiation therapy may be a safe and effective treatment option for locally recurrent rectal cancer and may serve as an alternative to surgery. PMID- 27375167 TI - Toward Prostate Cancer Contouring Guidelines on Magnetic Resonance Imaging: Dominant Lesion Gross and Clinical Target Volume Coverage Via Accurate Histology Fusion. AB - PURPOSE: Defining prostate cancer (PCa) lesion clinical target volumes (CTVs) for multiparametric magnetic resonance imaging (mpMRI) could support focal boosting or treatment to improve outcomes or lower morbidity, necessitating appropriate CTV margins for mpMRI-defined gross tumor volumes (GTVs). This study aimed to identify CTV margins yielding 95% coverage of PCa tumors for prospective cases with high likelihood. METHODS AND MATERIALS: Twenty-five men with biopsy confirmed clinical stage T1 or T2 PCa underwent pre-prostatectomy mpMRI, yielding T2-weighted, dynamic contrast-enhanced, and apparent diffusion coefficient images. Digitized whole-mount histology was contoured and registered to mpMRI scans (error <=2 mm). Four observers contoured lesion GTVs on each mpMRI scan. CTVs were defined by isotropic and anisotropic expansion from these GTVs and from multiparametric (unioned) GTVs from 2 to 3 scans. Histologic coverage (proportions of tumor area on co-registered histology inside the CTV, measured for Gleason scores [GSs] >=6 and >=7) and prostate sparing (proportions of prostate volume outside the CTV) were measured. Nonparametric histologic-coverage prediction intervals defined minimal margins yielding 95% coverage for prospective cases with 78% to 92% likelihood. RESULTS: On analysis of 72 true positive tumor detections, 95% coverage margins were 9 to 11 mm (GS >= 6) and 8 to 10 mm (GS >= 7) for single-sequence GTVs and were 8 mm (GS >= 6) and 6 mm (GS >= 7) for 3-sequence GTVs, yielding CTVs that spared 47% to 81% of prostate tissue for the majority of tumors. Inclusion of T2-weighted contours increased sparing for multiparametric CTVs with 95% coverage margins for GS >=6, and inclusion of dynamic contrast-enhanced contours increased sparing for GS >=7. Anisotropic 95% coverage margins increased the sparing proportions to 71% to 86%. CONCLUSIONS: Multiparametric magnetic resonance imaging-defined GTVs expanded by appropriate margins may support focal boosting or treatment of PCa; however, these margins, accounting for interobserver and intertumoral variability, may preclude highly conformal CTVs. Multiparametric GTVs and anisotropic margins may reduce the required margins and improve prostate sparing. PMID- 27375168 TI - Safety and Efficacy of Radiation Therapy in Advanced Melanoma Patients Treated With Ipilimumab. AB - PURPOSE: Ipilimumab and radiation therapy (RT) are standard treatments for advanced melanoma; preclinical models suggest the potential for synergy. However, limited clinical information exists regarding safety and optimal timing of the combination. METHODS AND MATERIALS: We reviewed the records of consecutive patients with unresectable stage 3 or 4 melanoma treated with ipilimumab. Patients were categorized as having received RT or not. Differences were estimated between these 2 cohorts. RESULTS: We identified 88 patients treated with ipilimumab. At baseline, the ipilimumab-plus-RT group (n=44) had more unfavorable characteristics. Despite this, overall survival, progression-free survival, and both immune-related and non-immune-related toxicity were not statistically different (P=.67). Patients who received ipilimumab before RT had an increased duration of irradiated tumor response compared with patients receiving ipilimumab after RT (74.7% vs 44.8% at 12 months; P=.01, log-rank test). In addition, patients receiving ablative RT had non-statistically significantly improved median overall survival (19.6 vs 10.2 months), as well as 6-month (95.1% vs 72.7%) and 12-month (79.7% vs 48.5%) survival rates, compared with those treated with conventionally fractionated RT. CONCLUSIONS: We found that both ablative and conventionally fractionated RT can be safely administered with ipilimumab without a clinically apparent increase in toxicity. Patients who received ipilimumab before RT had an increased duration of irradiated tumor response. PMID- 27375169 TI - Computed Tomography-Planned High-Dose-Rate Brachytherapy for Treating Uterine Cervical Cancer. AB - PURPOSE: To evaluate the long-term results of computed tomography (CT)-planned high-dose-rate (HDR) brachytherapy (BT) for treating cervical cancer patients. METHODS AND MATERIALS: CT-planned HDR BT was performed according to the adapted Group European de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) recommendations in 216 consecutive patients with locally advanced cervical cancer, International Federation of Gynecology and Obstetrics (FIGO) stage IB to IVA, who were treated with conformal external beam radiation therapy and concomitant chemotherapy. We analyzed outcomes and late side effects evaluated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Subjective, Objective, Management, Analysis evaluation scoring system and compared them with the results from a historical group. RESULTS: The median age was 56 years (range, 32-83 years). The median follow-up time for living patients was 52 months (range 37-63 months). The 5-year cumulative incidence function for the local recurrence rate for patients with FIGO II and III was 5.5% and 20%, respectively (P=.001). The 5-year rates of overall survival (OS) and disease-free survival (DFS) were 66.4% and 58.5%, respectively. The relative risk of failure for OS and DFS for FIGO III in relation to FIGO II was 2.24 (P=.003) and 2.6 (P=.000) and for lymph node enlargement was 2.3 (P=.002) and 2 (P=.006), respectively. In 2 patients, rectovaginal fistula occurred, and in 1 patient, vesicovaginal fistula occurred without local progression. Comparison of late adverse effects in patients treated according to the GEC-ESTRO recommendations and in the historical group revealed a reduction in fistula formation of 59% and also a reduction in rectal grade 3 to 4 late toxicity of >59%. CONCLUSIONS: This is the largest report with mature data of CT-planned BT HDR for the treatment of cervical cancer with good local control and acceptable toxicity. In comparison with the historical series, there is a substantial benefit in terms of severe late effects. FIGO III and enlarged lymph nodes in positron emission tomography-CT/CT are negative prognostic factors, both with a relative risk of failure of approximately 2. PMID- 27375170 TI - Suppressive Effects of Glucose-Dependent Insulinotropic Polypeptide on Cardiac Hypertrophy and Fibrosis in Angiotensin II-Infused Mouse Models. AB - BACKGROUND: Activation of glucose-dependent insulinotropic polypeptide receptor (GIPR) has been shown to be protective against atherosclerosis. However, effects of GIP on the heart have remained unclear. To address this question, in vitro and in vivo experiments were conducted. METHODS AND RESULTS: In isolated mouse cardiomyocytes, GIPR mRNA was detected by reverse transcription-polymerase chain reaction, and GIP stimulation increased adenosine 3',5'-cyclic monophosphate production. In apolipoprotein E-knockout mice, infusion of angiotensin II (AngII; 2,000 ng.kg(-1).min(-1)) significantly increased the heart weights, and co administration of GIP (25 nmol.kg(-1).day(-1)) reversed this increase (both P<0.01). In the left ventricular walls, GIP suppressed AngII-induced cardiomyocyte hypertrophy by 34%, apoptosis by 77%, and interstitial fibrosis by 79% (all P<0.01). Furthermore, GIP reduced AngII-induced expression of transforming growth factor-beta1 (TGF-beta1) and hypoxia inducible factor-1alpha. In wild-type mice, cardiac hypertrophy was induced by AngII to a lesser extent, and prevented by GIP. In contrast, GIP did not show any cardioprotective effect against AngII-induced cardiac hypertrophy in GIPR-knockout mice. In an in vitro experiment using mouse cardiomyocytes, GIP suppressed AngII-induced mRNA expression of B-type natriuretic peptide and TGF-beta1. CONCLUSIONS: It was demonstrated that cardiomyocytes represent a direct target of GIP action in vitro, and that GIP ameliorated AngII-induced cardiac hypertrophy via suppression of cardiomyocyte enlargement, apoptosis, and fibrosis in vivo. (Circ J 2016; 80: 1988-1997). PMID- 27375171 TI - [Cutaneous tuberculosis of the ear due to Mycobacterium bovis]. AB - INTRODUCTION: Isolated cutaneous tuberculosis is uncommon, accounting for only 0.14 to 5% of Mycobacterium tuberculosis infections. We report a rare case of ear cutaneous tuberculosis due to Mycobacterium bovis in an immunocompetent woman. CASE REPORT: A 59-year-old woman presented an erythematous and scaly lesion of the ear present for two years. The histological findings were compatible with a diagnosis of sarcoidosis, with non-necrotic granuloma. After failure of dermal corticosteroid therapy, a further biopsy identified M. bovis; the patient was cured following anti-tubercular treatment. DISCUSSION: Ear lesions are predominantly associated with tumors, fungal infections, chondritis, lupus and sarcoidosis. The ear, like the face in general, is a classic localization of lupus vulgaris, a chronic form of confined tuberculosis infection with progressive evolution. The paucibacillary nature of these lesions is the reason why their diagnosis is based in some cases on clinical, histological and immunological findings without bacteriological evidence. However, given the potential therapeutic implications, it is important to push the microbiological analysis as far as possible. In our case, culture and identification provided evidence of M. bovis infection, enabling suitable and effective therapy to be given. PMID- 27375172 TI - Identification of reliable reference genes for quantitative gene expression studies in oral squamous cell carcinomas compared to adjacent normal tissues in the F344 rat model. AB - Oral squamous cell carcinomas (OSCCs) induced in F344 rats by 4-nitroquinoline-1 oxide (4-NQO) demonstrate considerable phenotypic similarity to human oral cancers and the model has been widely used for carcinogenesis and chemoprevention studies. Molecular characterization of this model needs reliable reference genes (RGs) to avoid false- positive and -negative results for proper interpretation of gene expression data between tumor and adjacent normal tissues. Microarray analysis of 11 pairs of OSCC and site-matched phenotypically normal oral tissues from 4-NQO-treated rats identified 10 stably expressed genes in OSCC compared to adjacent normal tissues (p>0.5, CV<15%) that could serve as potential RGs in this model. The commonly used 27 RGs in the rat were also analyzed based on microarray data and most of them were found unsuitable for RGs in this model. Traditional RGs such as ACTB and GAPDH were significantly altered in OSCC compared to adjacent normal tissues (p<0.01, n=11); however, the Hsp90ab1 was ranked as the best RG candidate and the combination of Hsp90ab1 and HPRT1 was identified by NormFinder to be a superior reference for gene normalization among the commonly used RGs. This result was also validated by RT-PCR based on the selected top RG candidate pool. These data suggest that there are no common RGs suitable for different models and RG(s) should be identified before gene expression analysis. We successfully identified Hsp90ab1 as a stable RG in 4-NQO-induced OSCC compared to adjacent normal tissues in F344 rats. The combination of two stably expressed genes may be a better option for gene normalization in tissue samples. PMID- 27375173 TI - PEDiDBS: The pediatric international deep brain stimulation registry project. AB - BACKGROUND: Interactive neuromodulation represents the evolving frontier in surgical treatment of a variety of disorders involving the sensory organs and nervous system. Building on the advances of pioneering neurologists and neurosurgeons, progress has been made since the introduction of deep brain stimulation (DBS). Microelectrode recording has greatly aided our understanding of the underlying pathogenesis of movement disorders and the effects of electrical stimulation. The introduction of image - guided systems to provide targeted, controlled neuro-stimulation to specific brain areas is an emerging technique for implantation and may have special appeal for pediatric patients. RATIONALE/AIM: DBS is generally accepted as a treatment for some forms of childhood dystonia. Its potential role in other pediatric movement disorders is less well established. This is important, as most forms of dystonia begin in childhood or adolescence and many are inadequately responsive to current pharmacotherapy and other interventions. Nonetheless, many aspects of deep brain stimulation need clarification. CONCLUSION: This can only be accomplished through an organized platform for data sharing that will allow questions to be asked and hopefully answered, with the ultimate goal of developing evidence based practice based guidelines elucidating the role of DBS in pediatric patients. PMID- 27375175 TI - Mixing of exciton and charge-transfer states in light-harvesting complex Lhca4. AB - Lhca4 is one of the peripheral antennae of higher plant photosystem I and it is characterized by the presence of chlorophyll a with absorption and emission bands around 30 nm red-shifted compared to those of the other chlorophylls associated with plant complexes. In this work we have investigated the origin of this red shift by using the recent structure of Lhca4 (Qin et al., Science, 2015, 348, 989) to build an exciton model that includes a charge-transfer (CT) state mixed with the excited-state manifold. A simultaneous quantitative fit of absorption, linear dichroism, fluorescence, and Stark absorption spectra of the wild-type Lhca4 and NH mutant (where the sites involved in CT are affected) enables us to determine the origin of the CT state and explore its spectral signatures. A huge borrowing of dipole strength by the CT, accompanied by anomalous broadening and red-shifting of the fluorescence as well as dramatic changes in the Stark spectrum, can be accounted for by a model implying an exciton-type mixing between excited states and CT states. PMID- 27375174 TI - Alcohol Vapor Inhalation as a Model of Alcohol-Induced Organ Disease. AB - BACKGROUND: Chronic intermittent ethanol vapor (CIEV) exposure has been used extensively to produce rodent models of alcohol dependence, but unlike other models of alcohol abuse, CIEV has not been assessed as a model of end-organ damage. The purpose of this study was to characterize the effects of CIEV on peripheral organ systems affected by alcohol abuse, including the liver, lungs, and cardiovascular system. METHODS: Adult male Sprague-Dawley rats were exposed to daily CIEV for a period of 8 weeks (14HR ON/10HR OFF), producing blood alcohol levels of ~200 mg/dl. Controls were exposed to room air. After 8 weeks, echocardiography was performed to assess cardiac function. Indices of liver injury (alanine and aspartate aminotransferases [ALT and AST]; cytochrome p450 2E1 [CYP2E1]; alcohol dehydrogenase [ADH]; Oil Red O and triglyceride content; lipid peroxidation; inflammatory cytokine expression; and macrophage infiltration), and lung inflammatory cell count, proinflammatory cytokine expression, and lipid peroxidation were measured. RESULTS: Left ventricular posterior wall thickness was significantly decreased, and systolic blood pressure was significantly elevated by CIEV compared with air controls. CIEV led to a significant increase in plasma ALT and triglycerides compared with room air controls. CIEV did not affect liver triglyceride content, lipid staining or peroxidation, but increased CYP2E1 and chemokine (C-C motif) ligand 2 (CCL2) protein expression, while decreasing ADH expression. CIEV significantly increased numbers of both polymorphonuclear neutrophils and lymphocytes in the bronchoalveolar lavage fluid, indicative of pulmonary inflammation. However, CIEV did not produce significant changes in lung mass, pulmonary lipid peroxidation, inflammatory cytokine expression, or edema. CONCLUSIONS: These results show that CIEV produces hepatic, pulmonary, and cardiovascular effects in rats similar to those found in other models of chronic alcohol administration. Alcohol vapor administration is a novel method of alcohol-induced tissue injury with high potential for widespread use in alcohol toxicology research. PMID- 27375176 TI - Identification of factors contributing to phenotypic divergence via quantitative image analyses of autosomal recessive woolly hair/hypotrichosis with homozygous c.736T>A LIPH mutation. AB - BACKGROUND: Autosomal recessive woolly hair/hypotrichosis (ARWH/H) is caused by mutations in LIPH. Homozygotes for the LIPH c.736T>A (p.C246S) mutation, the most prevalent genotype in Japanese patients, present varying degrees of hair loss; however, determinants of this phenotypic diversity remain elusive. OBJECTIVES: To establish methodologies for quantitative assessment of clinical severity and provide a detailed characterization to elucidate the factors contributing to phenotypic divergence. METHODS: Digital image analyses were conducted to convert clinical severities into numerical values. Eight patients with ARWH/H were classified into three groups (mild, severe, very severe), based on severity scores. Dermoscopic images were collected and assessed for total hair numbers and hair thickness for intergroup comparisons. RESULTS: The image analysis detected a difference in hair thickness but not in total hair numbers, between mild and severe cases. A marked decrease in total hair number was noted in an atypical very severe case. Histopathologically, a patient with a mild case demonstrated hair miniaturization and a high telogen/anagen ratio without a decrease in total hair count, endorsing dermoscopic observations. Two children demonstrated spontaneous improvement without an increase in total hair numbers, and two adults responded well to topical minoxidil with increased total hair numbers and hair thickness. CONCLUSIONS: The difference in the frequency of underdeveloped hairs may be a major factor contributing to the clinical diversity of hair sparseness in LIPH c.736T>A homozygotes with ARWH/H. Hence, pharmacological modification to thicken existing fine hairs may provide a therapeutic strategy. PMID- 27375177 TI - Effect of clpP and clpC deletion on persister cell number in Staphylococcus aureus. AB - Staphylococcus aureus is responsible for a wide variety of infections that include superficial skin and soft tissue infections, septicaemia, central nervous system infections, endocarditis, osteomyelitis and pneumonia. Others have demonstrated the importance of toxin-antitoxin (TA) modules in the formation of persisters and the role of the Clp proteolytic system in the regulation of these TA modules. This study was conducted to determine the effect of clpP and clpC deletion on S. aureus persister cell numbers following antibiotic treatment. Deletion of clpP resulted in a significant decrease in persister cells following treatment with oxacillin and erythromycin but not with levofloxacin and daptomycin. Deletion of clpC resulted in a decrease in persister cells following treatment with oxacillin. These differences were dependent on the antibiotic class and the CFU ml-1 in which the cells were treated. Persister revival assays for all the bacterial strains in these studies demonstrated a significant delay in resumption of growth characteristic of persister cells, indicating that the surviving organisms in this study were not likely due to spontaneous antibiotic resistance. Based on our results, ClpP and possibly ClpC play a role in persister cell formation or maintenance, and this effect is dependent on antibiotic class and the CFU ml-1 or the growth phase of the cells. PMID- 27375178 TI - Experimental evolution in fungi: An untapped resource. AB - Historically, evolutionary biology has been considered an observational science. Examining populations and inferring evolutionary histories mold evolutionary theories. In contrast, laboratory evolution experiments make use of the amenability of traditional model organisms to study fundamental processes underlying evolution in real time in simple, but well-controlled, environments. With advances in high-throughput biology and next generation sequencing, it is now possible to propagate hundreds of parallel populations over thousands of generations and to quantify precisely the frequencies of various mutations over time. Experimental evolution combines the ability to simultaneously monitor replicate populations with the power to vary individual parameters to test specific evolutionary hypotheses, something that is impractical or infeasible in natural populations. Many labs are now conducting laboratory evolution experiments in nearly all model systems including viruses, bacteria, yeast, nematodes, and fruit flies. Among these systems, fungi occupy a unique niche: with a short generation time, small compact genomes, and sexual cycles, fungi are a particularly valuable and largely untapped resource for propelling future growth in the field of experimental evolution. Here, we describe the current state of fungal experimental evolution and why fungi are uniquely positioned to answer many of the outstanding questions in the field. We also review which fungal species are most well suited for experimental evolution. PMID- 27375179 TI - [Congenital neuromuscular diseases with neonatal respiratory failure excluding myotonic dystrophy type 1 and infantile spinal muscular atrophy. Diagnosis strategy according to a 19-child series]. AB - Apart from spinal muscular atrophy (SMA) and myotonic dystrophy type 1 (DM1), congenital neuromuscular diseases with early neonatal symptoms mean diagnostic and prognostic challenges mainly when infants require ventilatory support. OBJECTIVES: Consider a standardized strategy for infants suspected of congenital neuromuscular disease from analysis of the literature and retrospective experience with floppy and ventilatory support-dependent infants, after exclusion of well-known diseases (DM1, SMA). PATIENTS AND METHODS: Floppy infants requiring ventilatory support in their 1st month of life, but showing no evidence of DM1, SMA, Prader-Willi syndrome, or encephalopathy. The retrospective multicenter study was based on the response of regional referent neuropediatricians in the Reference Centre for Neuromuscular Diseases of Greater Southwest France to an inquiry about prenatal and perinatal history, investigations, diagnosis, and outcome of the child and family. It was conducted between 2007 and 2012. RESULTS: Among the 19 newborns studied, all had severe hypotonia. Prenatal and perinatal features were similar. Their outcome was generally severe: the median survival as measured by the Kaplan-Meier method was 6.9 months. Thirteen children died at a median age of 61 days; ten of them were treated with a palliative procedure. Five children had achieved respiratory independence but suffered from a small delay in motor development. Among the three children who continuously required ventilatory support, only one survived (follow-up period: 23 months); he was the only one undergoing tracheostomy in the cohort. Diagnostic processes were different, leading to pathological and genetic diagnosis for only six infants. There was only histological orientation for seven and no specific diagnostic orientation for the last six. These difficulties have led us to propose an exploration process based on the literature. CONCLUSION: This study highlights difficulties in obtaining a diagnosis and a precise prognosis for floppy ventilated infants. An exploration-standardized process for infants suspected of congenital neuromuscular diseases was made in order to standardize procedures. It could be used as a tool for all professionals involved. PMID- 27375180 TI - CCL2 level is elevated with metabolic syndrome and CXCL10 level is correlated with visceral fat area in obese children. AB - Recent studies revealed that obesity is a low-grade, chronic inflammatory state that is accompanied by the enhanced production of multiple chemokines. In particular, metabolic syndrome (MS) and visceral adipose tissue (VAT) accumulation are significantly associated with certain chemokines in adults. However, little is known regarding this association in obese children. The aim of this study was to investigate the relationship between circulating chemokine levels and both MS and VAT accumulation in obese children. Forty-four obese schoolchildren (26 boys) with a percentage of overweight (POW) exceeding 20 were evaluated. The median age was 11.4 years (range: 6.8-16.5 years). Blood samples were drawn after overnight fasting, and serum chemokine levels (CCL2, CCL5 and CXCL10) were quantitated. Visceral fat area (VFA) determinations were conducted using computed tomography. The results showed that the median BMI Z-score, POW, waist circumference and VFA of the subjects were 2.24 SD, 49.8%, 88.3 cm and 80.8 cm2, respectively. Eighteen were diagnosed with MS. CCL2 was significantly increased in MS subjects compared with non-MS subjects (p<0.05). CXCL10 was positively correlated with VFA (r=0.425, p<0.01). There were no significant correlations between age and chemokine levels. We showed that CCL2 levels were elevated in MS and CXCL10 levels were associated with VFA in obese children. Our results suggest that CCL2 and CXCL10 play important roles in the progression of obesity-related metabolic complications in children. PMID- 27375181 TI - Detection of prostate cancer using a voltammetric electronic tongue. AB - A simple method based on the multivariate analysis of data from urine using an electronic voltammetric tongue is used to detect patients with prostate cancer. A sensitivity of 91% and a specificity of 73% were obtained to distinguish the urine from cancer patients and the urine from non-cancer patients. PMID- 27375182 TI - Singlet oxygen production by combining erythrosine and halogen light for photodynamic inactivation of Streptococcus mutans. AB - BACKGROUND: Photodynamic inactivation of microorganisms is based on a photosensitizing substance which, in the presence of light and molecular oxygen, produces singlet oxygen, a toxic agent to microorganisms and tumor cells. This study aimed to evaluate singlet oxygen quantum yield of erythrosine solutions illuminated with a halogen light source in comparison to a LED array (control), and the photodynamic effect of erythrosine dye in association with the halogen light source on Streptococcus mutans. METHODS: Singlet oxygen quantum yield of erythrosine solutions was quantified using uric acid as a chemical-probe in an aqueous solution. The in vitro effect of the photodynamic antimicrobial activity of erythrosine in association with the halogen photopolimerizing light on Streptococcus mutans (UA 159) was assessed during one minute. Bacterial cultures treated with erythrosine alone served as negative control. RESULTS: Singlet oxygen with 24% and 2.8% degradation of uric acid in one minute and a quantum yield of 0.59 and 0.63 was obtained for the erythrosine samples illuminated with the halogen light and the LED array, respectively. The bacterial cultures with erythrosine illuminated with the halogen light presented a decreased number of CFU mL(-1) in comparison with the negative control, with minimal inhibitory concentrations between 0.312 and 0.156mgmL(-1). CONCLUSIONS: The photodynamic response of erythrosine induced by the halogen light was capable of killing S. mutans. Clinical trials should be conducted to better ascertain the use of erythrosine in association with halogen light source for the treatment of dental caries. PMID- 27375183 TI - Plum-blossom needling promoted PpIX fluorescence intensity from 5-aminolevulinic acid in porcine skin model and patients with actnic keratosis. AB - BACKGROUND AND OBJECTIVES: Plum-blossom needling might enhance transdermal penetration of topically applied drugs by creating vertical channels. The purpose of this study was to evaluate drug delivery assisted by plum-blossom needling comparing with CO2 laser ablative fractional resurfacing (AFR) using 5 aminolevulinic acid (5-ALA), a porphyrin precursor, as a test drug. MATERIALS AND METHODS: Ex vivo porcine skin was treated with plum-blossom needle(HWATO, Suzhou medical supplies factory Co., Ltd. China) or CO2 laser AFR before topical application of 20% 5-ALA(Sigma-Aldrich, Co., USA)cream, placebo cream and no cream. ALA-induced porphyrin fluorescence was measured by fluorescence microscopy at skin depths down to 1800MUm. Needling was done by tapping the skin vertically from 5cm high above quickly. AFR was performed with a 10.6MUm wavelength prototype CO2 laser, using stacked single pulses of 3 millisecond and 91.6mJ per pulse. Plum-blossom needling after ALA application was also done. Fluorescence intensity on lesion surface was examined by curalux spectrum analyzer (Laser Institute of Munich University, Germany) and VAS pain score was recorded in a randomized split-lesion clinical trial including 6 patients, 8 actinic keratosis lesions. RESULTS: AFR created regular cone-shaped channels surrounded by a 70MUm thin layer of thermally coagulated dermis, respectively. The cone is approximately 200MUm in diameter at the opening and 1850MUm in depth. Plum blossom needle created irregular cone-shaped channels of approximately 180MUm in diameter at the opening and it always drags a tail-which was shaped from the closed deeper channels. There was no porphyrin fluorescence in placebo cream or untreated skin sites. Plum-blossom needling followed by ALA application enhanced drug delivery with significantly higher porphyrin fluorescence at the edge of hole (P<0.005) and 100MUm far from the hole (P=0.000) versus AFR followed by ALA application at skin depths of 120 and 500MUm. Needling after ALA application presented higher porphyrin fluorescence at the edge of hole at skin depths of 120MUm (P<0.005) and lower porphyrin fluorescence at 1000MUm deep hole edge, and 100MUm far from the hole at 120MUm, 500MUm and 1000MUm depths versus AFR followed by ALA application (P<0.005). Skin massage after ALA application did not affect ALA-induced porphyrin fluorescence after pretreatment of plum-blossom needling or AFR. ALA application after plum-blossom needling was better than before plum blossom needling. The clinical trial showed that the surface fluorescence intensity was stronger in needle-pretreated-lesion than in laser-pretreated lesion. While the VAS pain score between needle treatment and laser treatment was almost the same. CONCLUSIONS: Plum-blossom needling facilitates delivery of topical ALA into the dermis. It may help ALA to diffuse a little more broadly than AFR does in superficial dermis and obtain similar clinical effect with a much lower cost. Plum-blossom needling treatment appears to be a clinically practical and economical means for enhancing transdermal delivery of ALA, a photodynamic therapy drug, and presumably many other topical skin medications. PMID- 27375184 TI - Verteporfin photodynamic therapy for the treatment of choroidal haemangioma associated with Sturge-Weber syndrome. AB - PURPOSE: Choroidal haemangiomas associated with Sturge Weber syndrome most commonly affect the posterior pole and consequently result in amblyopia. Treatment is often challenging but usually unwarranted unless there is visual deterioration caused by exudative or neovascular complications. The main objective is to demonstrate the effectivity of photodynamic therapy in this context. DESIGN AND METHODS: Retrospective analysis of prospectively collected data regarding verteporfin photodynamic therapy (PDT) in the treatment of patients with choroidal haemangiomas associated with Sturge Weber syndrome. RESULTS: Six patients (4 male, 2 female) with a median age of 28 years (range, 23 67) had a mean tumour belly diameter of 12.2mm (range, 9-16.8). There was regression of the tumour in all cases, albeit after 3 treatments in a single case. The exudative retinal detachment resolved in 2 out of 3 patients. Visual outcome improved in 3 patients, remaining poor but stable in the other three, due to pre-existing amblyopia. CONCLUSIONS: PDT is an effective and safe treatment for patients with choroidal haemangioma associated with Sturge-Weber syndrome. PMID- 27375185 TI - 2D Black Phosphorus/SrTiO3 -Based Programmable Photoconductive Switch. AB - A novel heterostructure is designed by stacking 2D black phosphorus (BP) on a SrTiO3 substrate. The device demonstrates programmable photoconductive switching under illumination of UV and red light. The light-tunable persistent photoconductivity exhibits a large on/off ratio exceeding 10(5) . The persistent state shows almost no relaxation or decay at low temperature. These features are suitable for a new generation of optoelectronic devices for memory application. PMID- 27375186 TI - Bicuspid and Unicuspid Aortic Valve: Fate of Moderate/Severe Mixed Aortic Valve Disease. AB - OBJECTIVES: There is a paucity of data about mixed aortic valve disease (MAVD) in patients with bicuspid/unicuspid aortic valve (BAV). This study sought to describe the outcomes of patients with moderate/severe MAVD. METHODS: We queried our database for patients with BAV and moderate/severe MAVD seen between 1994 and 2013. We excluded patients with baseline New York Heart Association (NYHA) III/IV symptoms, left ventricular ejection fraction <50%, aortic dimension >50 mm, and significant disease of other valves. The purpose of the study was to determine the freedom from NYHA III/IV symptoms and aortic valve replacement (AVR). RESULTS: We identified 138 patients with moderate/severe MAVD; mean age was 51 +/ 12 years; 112 (81%) were males; and follow-up was 8.5 +/- 4 years. Ninety-two patients (67%) underwent AVR within 3.7 +/- 2.5 years. Mechanical prostheses were implanted in 73 patients (79%); 22 patients (26%) and 36 patients (39%) had concomitant coronary artery bypass graft and aorta replacement during AVR respectively. There were no surgical deaths. Freedom from AVR was 84%, 51%, and 20% at 1, 5 and 10 years respectively. Predictors of AVR were age at presentation (hazard ratio [HR] 5.22; confidence interval [CI] 3.10 to 6.64) for every decade increase in age; and having severe stenosis or regurgitation at the time of presentation (HR 1.32; CI 1.05 to 3.16). CONCLUSIONS: Age and disease severity should be incorporated in the risk assessment of BAV patients with MAVD, and patients with both risk factors should be monitored closely. PMID- 27375188 TI - Recent advances in catalytic decarboxylative acylation reactions via a radical process. AB - The decarboxylative cross-coupling reactions of carboxylic acids have emerged as an efficient strategy for the C-C bond and C-X bond formations. In this field, the decarboxylative cross-coupling of alpha-keto acids has been developed as an attractive strategy to introduce a carbonyl group into versatile organic molecules. In particular, radical-mediated decarboxylative reactions have attracted much attention of chemists owing to their mild conditions, excellent functional group tolerance and high reactivity. In this review, we highlight the recent advances in the radical decarboxylative acylation reactions of alpha-keto acids. PMID- 27375187 TI - Dietary beta-glucan enhances the contents of complement component 3 and factor B in eggs of zebrafish. AB - beta-glucan has been shown to increase non-specific immunity and resistance against infections or pathogenic bacteria in several fish species, but no information is available regarding its trans-generational effects to date. Here we clearly demonstrated that beta-glucan enhanced the contents of immune-relevant molecules C3 and Bf in eggs of zebrafish, and the embryos derived from beta-1,3 glucan-treated zebrafish were more resistant to bacterial challenge than control embryos. Moreover, the transferred C3 and Bf were directly associated with the antimicrobial defense of early embryos. In addition, feeding female zebrafish with beta-glucan had little detrimental effects on the number of spawned eggs and their embryonic development. Collectively, these data show for the first time that beta-glucan can be safely used to promote the non-specific immunity in offspring of fishes. PMID- 27375189 TI - An apolar Pistacia lentiscus L. leaf extract: GC-MS metabolic profiling and evaluation of cytotoxicity and apoptosis inducing effects on SH-SY5Y and SK-N BE(2)C cell lines. AB - In the course of a cytotoxicity screening of Mediterranean plants vs. neuroblastoma cells, Pistacia lentiscus was of interest. Pl-C extract, prepared from dried leaves by ultrasound assisted maceration (UAM) in chloroform, was profiled through using GC-MS techniques. To evaluate Pl-C cytotoxicity towards SH SY5Y and SK-N-BE(2)-C cell lines, MTT, SRB and LDH assays were performed. The caspase-3 activation, DNA fragmentation, as well as micronucleation, were also evaluated. The Pl-C oxidant/antioxidant ability was estimated using different methods. The extract, rich in pentacyclic triterpenes, inhibited mitochondrial redox activity and cell viability of the tested cell lines. LDH assay established that Pl-C did not affect the cell membrane integrity. Indeed, it was able to activate caspase-3 and to cause a ladder pattern of DNA. Western blotting analysis showed that Pl-C processed caspase-3 providing two cleavage products of approximately 20 and 17-kDa, whose densitometric evaluation highlighted that Pl-C was more effective than vinblastine by 3-fold. The pro-apoptotic effect could be related to a disturbance in cell redox balance. In fact, it increased intracellular ROS production, GSSG/GSH ratio and the formation of lipoperoxidation products. The data obtained prompted to further investigate and assess the in vivo efficacy of Pl-C to prevent and/or treat neuroblastoma. PMID- 27375190 TI - Curcumin attenuates quinocetone induced apoptosis and inflammation via the opposite modulation of Nrf2/HO-1 and NF-kB pathway in human hepatocyte L02 cells. AB - The potential toxicity of quinocetone (QCT) has raised widely concern, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on QCT induced apoptosis and the underlying mechanism in human hepatocyte L02 cells. The results showed that QCT treatment significantly decreased the cell viability of L02 cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by curcumin pre-treatment at 1.25, 2.5 and 5 MUM. Compared to the QCT alone group, curcumin pre-treatment significantly attenuated QCT induced oxidative stress, mitochondrial dysfunction and apoptosis. In addition, curcumin pretreatment markedly attenuated QCT-induced increase of iNOS activity and NO production in a dose-dependent manner. Meanwhile, curcumin pretreatment markedly down-regulated the expression of nuclear factor -kB (NF-kB) and iNOS mRNAs, but up-regulated the expressions of Nrf2 and HO-1 mRNAs, compared to the QCT alone group. Zinc protoporphyrin IX, a HO-1 inhibitor, markedly partly abolished the cytoprotective effect of curcumin against QCT-induced caspase activation, NF-kB mRNA expression. These results indicate that curcumin could effectively inhibit QCT induced apoptosis and inflammatory response in L02 cells, which may involve the activation of Nrf2/HO-1 and inhibition of NF-kB pathway. PMID- 27375192 TI - Mechanisms of Acetaminophen Hepatotoxicity: Do We Need JNK for Cell Death? PMID- 27375191 TI - miRNAs as common regulators of the transforming growth factor (TGF)-beta pathway in the preeclamptic placenta and cadmium-treated trophoblasts: Links between the environment, the epigenome and preeclampsia. AB - Preeclampsia (PE) is a pregnancy disorder characterized by high blood pressure and proteinuria that can cause adverse health effects in both mother and fetus. There is no current cure for PE other than delivery of the fetus/placenta. While the etiology is unknown, poor placentation due to aberrant signaling of growth and angiogenic factors has been postulated as a causal factor of PE. In addition, environmental contaminants, such as the metal cadmium (Cd), have been linked to placental toxicity and increased risk of developing PE. Here, we use a translational study design to investigate genomic and epigenomic alterations in both placentas and placental trophoblasts, focused on the angiogenesis-associated transforming growth factor-beta (TGF-beta) pathway. Genes within the TGF-beta pathway displayed increased expression in both the preeclamptic placenta and Cd treated trophoblasts. In addition, miRNAs that target the TGF-beta pathway were also significantly altered within the preeclamptic placenta and Cd-treated trophoblasts. Integrative analysis resulted in the identification of a subset of Cd-responsive miRNAs, including miR-26a and miR-155, common to preeclamptic placentas and Cd-treated trophoblasts. These miRNAs have previously been linked to PE and are predicted to regulate members of the TGF-beta pathway. Results from this study provide future targets for PE treatment. PMID- 27375194 TI - The Esophageal Microbiome in Eosinophilic Esophagitis. PMID- 27375193 TI - Pneumococcal Disease in Inflammatory Bowel Disease: Justification to Vaccinate at Diagnosis. PMID- 27375195 TI - An Unusual Cause of Recurrent Dysphagia. PMID- 27375196 TI - A Peculiar Lump in the Throat. PMID- 27375197 TI - Highly sensitive detection of leukemia cells based on aptamer and quantum dots. AB - Detection of leukemia at the early stage with high sensitivity is a significant clinical challenge for clinicians. In the present study, we developed a sensitive detector consisting of the product of oligonucleotides hybridized with semiconductor quantum dots (QDs) to generate a stronger fluorescent signal so that leukemic cells can be captured. In the present study, a biotin-modified Sgc8 aptamer was used to identify CCRF-CEM cells, and then biotin-appended QDs were labeled with the aptamer via streptavidin and biotin amplification interactions. We described the complex as QDs-bsb-apt. CEM and Ramos cells were used to assess the specificity and sensitivity of the novel complex. These results revealed that the complex could be more effective in diagnosing leukemia at the early stage. In conclusion, an innovative structure based on aptamer and QDs for leukemia diagnosis was provided. It has the potential to image tumor cells in vitro or in vivo and to realize the early diagnosis of disease. Furthermore, it may be used to provide guidance for clinicians to implement individualized patient therapy. PMID- 27375198 TI - Angiotensin II type 1 receptor blockade by telmisartan prevents stress-induced impairment of memory via HPA axis deactivation and up-regulation of brain-derived neurotrophic factor gene expression. AB - Physical and psychological aspects of chronic stress continue to be a persistent clinical problem for which new pharmacological treatment strategies are aggressively sought. By the results of our previous work it has been demonstrated that telmisartan (TLM), an angiotensin type 1 receptor (AT1) blocker (ARB) and partial agonist of peroxisome proliferator-activated receptor gamma (PPARgamma), alleviates stress-induced cognitive decline. Understanding of mechanistic background of this phenomenon is hampered by both dual binding sites of TLM and limited data on the consequences of central AT1 blockade and PPARgamma activation. Therefore, a critical need exists for progress in the characterization of this target for pro-cognitive drug discovery. An unusual ability of novel ARBs to exert various PPARgamma binding activities is commonly being viewed as predominant over angiotensin blockade in terms of neuroprotection. Here we aimed to verify this hypothesis using an animal model of chronic psychological stress (Wistar rats restrained 2.5h daily for 21days) with simultaneous oral administration of TLM (1mg/kg), GW9662 - PPARgamma receptor antagonist (0.5mg/kg), or both in combination, followed by a battery of behavioral tests (open field, elevated plus maze, inhibitory avoidance - IA, object recognition - OR), quantitative determination of serum corticosterone (CORT) and evaluation of brain-derived neurotrophic factor (BDNF) gene expression in the medial prefrontal cortex (mPFC) and hippocampus (HIP). Stressed animals displayed decreased recall of the IA behavior (p<0.001), decreased OR (p<0.001), substantial CORT increase (p<0.001) and significantly downregulated expression of BDNF in the mPFC (p<0.001), which were attenuated in rats receiving TLM and TLM+GW9662. These data indicate that procognitive effect of ARBs in stressed subjects do not result from PPAR-gamma activation, but AT1 blockade and subsequent hypothalamus-pituitary-adrenal axis deactivation associated with changes in primarily cortical gene expression. This study confirms the dual activities of TLM that controls hypertension and cognition through AT1 blockade. PMID- 27375199 TI - The normal modes of lattice vibrations of ice XI. AB - The vibrational spectrum of ice XI at thermal wavelengths using the CASTEP code, a first-principles simulation method, is investigated. A dual-track approach is constructed to verify the validity for the computational phonon spectrum: collate the simulated spectrum with inelastic neutron scattering experiments and assign the photon scattering peaks according to the calculated normal vibration frequencies. The 33 optical normal vibrations at the Brillouin center are illustrated definitely from the ab initio outcomes. The depolarizing field effect of the hydrogen bond vibrations at frequencies of 229 cm(-1) and 310 cm(-1) is found to agree well with the LST relationship. It is a convincing evidence to manifest the LO-TO splitting of hydrogen bonds in ice crystal. We attribute the two hydrogen bond peaks to the depolarization effect and apply this viewpoint to ordinary ice phase, ice Ih, which is difficult to analyse their vibration modes due to proton disorder. PMID- 27375200 TI - Nanosecond pulsed electric field (nsPEF) enhance cytotoxicity of cisplatin to hepatocellular cells by microdomain disruption on plasma membrane. AB - Previous studies showed nanosecond pulsed electric field (nsPEF) can ablate solid tumors including hepatocellular carcinoma (HCC) but its effect on cell membrane is not fully understood. We hypothesized nsPEF disrupt the microdomains on outer cellular membrane with direct mechanical force and as a result the plasma membrane permeability increases to facilitate the small molecule intake. Three HCC cells were pulsed one pulse per minute, an interval longer than nanopore resealing time. The cationized ferritin was used to mark up the electronegative microdomains, propidium iodide (PI) for membrane permeabilization, energy dispersive X-ray spectroscopy (EDS) for the negative cell surface charge and cisplatin for inner-cellular cytotoxicity. We demonstrated that the ferritin marked-microdomain and negative cell surface charge were disrupted by nsPEF caused-mechanical force. The cell uptake of propidium and cytotoxicity of DNA targeted cisplatin increased with a dose effect. Cisplatin gains its maximum inner-cellular cytotoxicity when combining with nsPEF stimulation. We conclude that nsPEF disrupt the microdomains on the outer cellular membrane directly and increase the membrane permeabilization for PI and cisplatin. The microdomain disruption and membrane infiltration changes are caused by the mechanical force from the changes of negative cell surface charge. PMID- 27375201 TI - Revisiting the phosphatidylethanolamine-binding protein (PEBP) gene family reveals cryptic FLOWERING LOCUS T gene homologs in gymnosperms and sheds new light on functional evolution. AB - Angiosperms and gymnosperms are two major groups of extant seed plants. It has been suggested that gymnosperms lack FLOWERING LOCUS T (FT), a key integrator at the core of flowering pathways in angiosperms. Taking advantage of newly released gymnosperm genomes, we revisited the evolutionary history of the plant phosphatidylethanolamine-binding protein (PEBP) gene family through phylogenetic reconstruction. Expression patterns in three gymnosperm taxa and heterologous expression in Arabidopsis were studied to investigate the functions of gymnosperm FT-like and TERMINAL FLOWER 1 (TFL1)-like genes. Phylogenetic reconstruction suggests that an ancient gene duplication predating the divergence of seed plants gave rise to the FT and TFL1 genes. Expression patterns indicate that gymnosperm TFL1-like genes play a role in the reproductive development process, while GymFT1 and GymFT2, the FT-like genes resulting from a duplication event in the common ancestor of gymnosperms, function in both growth rhythm and sexual development pathways. When expressed in Arabidopsis, both spruce FT-like and TFL1-like genes repressed flowering. Our study demonstrates that gymnosperms do have FT-like and TFL1-like genes. Frequent gene and genome duplications contributed significantly to the expansion of the plant PEBP gene family. The expression patterns of gymnosperm PEBP genes provide novel insight into the functional evolution of this gene family. PMID- 27375202 TI - Triple rule-out computed tomography for risk stratification of patients with acute chest pain. AB - AIMS: Clinical evidence supporting triple rule-out computed tomography (TRO-CT) for rapid screening of cardiovascular disease is limited. We investigated the clinical value of TRO-CT in patients with acute chest pain. METHODS: We retrospectively enrolled 1024 patients who visited the emergency department (ED) with acute chest pain and underwent TRO-CT using a 128-slice CT system. TRO-CT was classified as "positive" if it revealed clinically significant cardiovascular disease including obstructive coronary artery disease, pulmonary thromboembolism, or acute aortic syndrome. The clinical endpoint was occurrence of a major adverse cardiovascular event (MACE) within 30 days, defined by a composite of all cause death, myocardial infarction, revascularization, major cardiovascular surgery, or thrombolytic therapy. Clinical risk scores for acute chest pain including TIMI, GRACE, Diamond-Forrester, and HEART were determined and compared to the TRO-CT findings. RESULTS: TRO-CT revealed clinically significant cardiovascular disease in 239 patients (23.3%). MACE occurred in 119 patients (49.8%) with positive TRO CT and in 7 patients (0.9%) with negative TRO-CT (p < 0.001). Sensitivity, specificity, positive predictive value, and negative predictive value of TRO-CT was 95%, 88%, 54%, and 99%, respectively. TRO-CT was a better discriminator between patients with vs. without events as compared to clinical risk scores (c statistics = 0.91 versus 0.64 to 0.71; integrated discrimination improvement = 0.31 to 0.37; p < 0.001 for all comparisons). Patients with a negative TRO-CT showed shorter ED stay times and admission rates compared to patients with positive TRO-CT, irrespective of clinical risk scores (p < 0.001 for all comparisons). CONCLUSION: Triple rule-out CT has high predictive performance for 30-day MACE and permits rapid triage and low admission rates irrespective of clinical risk scores. PMID- 27375203 TI - A Small G Protein as a Novel Component of the Rice Brassinosteroid Signal Transduction. AB - Brassinosteroids (BRs) are a class of steroid hormones that are essential for plant growth and development. The BR signal transduction pathway in the dicot model plant Arabidopsis is well established, but the components connecting the BR signaling steps in rice have not been fully explored. For example, how the BR signaling is fine-tuned in rice, especially at the BR receptor level, is largely unknown. Here we show that OsPRA2, a rice small G protein, plays a repressive role in the BR signaling pathway. Lamina inclination, coleoptile elongation, and root inhibition assays indicated that rice plants with suppressed expression of OsPRA2 were more sensitive to exogenously applied brassinolide than the wild-type plants. Conversely, rice overexpressing OsPRA2 was less sensitive to exogenous brassinolide. Further study uncovered that OsPRA2 inhibited the dephosphorylation of, and thus inactivated the transcription factor BRASSINAZOLE-RESISTANT 1 (OsBZR1). More importantly, OsPRA2 was found to co-localize with and directly bind to rice BR receptor BRASSINOSTEROID-INSENSITIVE 1 (OsBRI1) at the plasma membrane. Additionally, the in vitro assays showed that OsPRA2 inhibits its autophosphorylation. This OsPRA2-OsBRI1 interaction led to the dissociation of OsBRI1 from its co-receptor OsBAK1, and abolished OsBRI1-mediated phosphorylation of OsBAK1. Together, these results reveal a possible working mechanism of OsPRA2 as a novel negative regulator on OsBRI1 and OsBZR1 and extend the knowledge about the regulatory mechanism of rice BR signaling. PMID- 27375204 TI - A Structural Bisulfite Assay to Identify DNA Cruciforms. AB - In the half century since the discovery of the double-helix structure of DNA, it has become increasingly clear that DNA functionality is based on much more than its sequence in a double-helical structure. Further advances have highlighted the importance of additional aspects of DNA structure: its packaging in the higher order chromatin structure, positioning of nucleosomes along the DNA, and the occurrence of non-helical DNA structures. Of these, the latter has been problematic to prove empirically. Here, we describe a method that uses non denaturing bisulfite sequencing on isolated Arabidopsis thaliana nuclei to determine the location of cytosines positioned outside the double helix as a result of non-B-form DNA structures. We couple this with computational methods and S1 nuclease digest to reliably identify stable, non-B-form, cruciform structures. This enables us to identify a palindrome in the promoter of FLOWERING LOCUS T that forms a stable non-B-form structure. The stronger conservation of the ability to form a non-helical secondary structure than of the sequence suggests that this structure is biologically relevant. PMID- 27375205 TI - New insights in Microbial Fuel Cells: novel solid phase anolyte. AB - For the development of long lasting portable microbial fuel cells (MFCs) new strategies are necessary to overcome critical issues such as hydraulic pump system and the biochemical substrate retrieval overtime to sustain bacteria metabolism. The present work proposes the use of a synthetic solid anolyte (SSA), constituted by agar, carbonaceous and nitrogen sources dissolved into diluted seawater. Results of a month-test showed the potential of the new SSA-MFC as a long lasting low energy consuming system. PMID- 27375206 TI - Long interspersed nuclear element (LINE)-1 methylation level as a molecular marker of early gastric cancer. AB - BACKGROUND/AIMS: This study was performed to examine the state of long interspersed nuclear element (LINE)-1 methylation level in gastric epithelial dysplasias (GEDs) and evaluate as a molecular marker for gastric carcinogenesis when it was compared with RUNX3 expression. METHODS: We examined 89 patients with GEDs subcategorized by the Vienna classification - 41 category 3 (low grade) and 48 category 4 (high grade/intramucosal carcinoma) lesion. All tissue samples were evaluated for RUNX3 immunohistochemical staining and the level of LINE-1 methylation. RESULTS: The rate of negative expression of RUNX3 in category 4 lesion was significant higher than category 3 (P<0.01). LINE-1 methylation level was statistically different between category 3 and category 4 lesion (P<0.01). Between positive and negative expression of RUNX3 in GEDs, there was a significant difference of LINE-1 methylation level (P<0.01). The area under the ROC curve (AUC) of LINE-1 methylation level for diagnosis of category 4 lesion was 0.88 (95% CI, 0.76-1.00). CONCLUSIONS: LINE-1 methylation level was well correlated with the Vienna classification of GED and it had a close relationship with the negative expression of RUNX3 in category 4 lesion. LINE-1 methylation level could be a good candidate for a molecular marker of early gastric cancer. PMID- 27375207 TI - Treatment sequence of synchronously (liver) metastasized colon cancer. AB - No standards for staging, systemic therapy or the timing of an operation are defined for patients newly diagnosed with synchronous metastases and a primary in the colon. An expert group of radiologists, medical, radiation and surgical oncologists therefore came together to discuss staging and treatment sequence for these patients and came up with a recommendation based on current evidence of potential therapeutic options. The discussion was organized to debate recommendations centred on 5 topics and therefore the position paper is built upon these titles and their subtitles. PMID- 27375208 TI - A SMAD4 mutation indicative of juvenile polyposis syndrome in a family previously diagnosed with Menetrier's disease. AB - BACKGROUND: Menetrier's disease (MD) is a rare disease with unknown aetiology, characterized by hypertrophic folds within the fundus and body of the stomach. AIMS: We investigated mutations of the candidate genes SMAD4, BMPR1A, TGF-alpha, and PDX1 within a family with MD. METHODS: A large 4-generation family with MD was identified. This family had 5 cases of MD, 1 case of MD and juvenile polyposis syndrome (JPS) and 3 cases of JPS. Participants provided saliva for DNA extraction and completed a health questionnaire designed to assess conditions that may be found in patients with MD. Following pedigree analysis, we sequenced the coding regions of the SMAD4 and BMPR1A genes and the regulatory regions of the TGF-alpha and PDX1 genes in affected and non-affected family members. RESULTS: No mutations were identified in the sequenced regions of BMPR1A, TGF alpha, or PDX1. A dominant 1244_1247delACAG mutation of SMAD4 was identified in each of the subjects with JPS as well as in each of the subjects with MD. Although this mutation segregated with disease, there were also unaffected/undiagnosed carriers. CONCLUSION: The 1244_1247delACAG mutation of SMAD4 is the cause of JPS and the likely cause of MD in a large family initially diagnosed with MD. PMID- 27375209 TI - The CRP level and STATE score predict survival in cirrhotic patients with hepatocellular carcinoma treated by transarterial embolization. AB - BACKGROUND: Prognostic biomarkers are needed in a heterogeneous population of patients with intermediate hepatocellular carcinoma (HCC) treated by transarterial (chemo)embolization. We aimed to validate the prognostic value of serum CRP levels and the STATE score, combining CRP, albumin and tumor burden. METHODS: All cirrhotic patients with HCC treated by a first transarterial (chemo)embolization (2007-2013) in our institution were included. Overall survival was assessed using the Kaplan-Meier method, log rank, univariate and multivariate Cox analyses. RESULTS: Among 157 patients included, 87% were men, 86% had Child Pugh A. Etiologies of liver disease included alcohol (57%), hepatitis C (32%), hepatitis B (11%) and/or metabolic syndrome (32%); 89% of patients were classified BCLC B. 33% of the patients had a CRP >1mg/dl and 33% a STATE score conferring poor prognosis (<18). Patients with CRP <1mg/dl had better overall survival than patients with CRP >1mg/dl (20 vs. 8 months, P=0.00186). Median overall survival was 6.73 months for patients with a STATE score <18 vs. 22.23 months for patients with STATE-score >=18 (P=0.0002). In multivariate analysis, a STATE score <18 was independently associated with increased mortality (HR: 2.06 (CI95%: 1.28-3.34), P=0.0031). CONCLUSION: In cirrhotic patients with HCC who underwent transarterial treatment, serum CRP level and STATE score at baseline can predict overall survival. PMID- 27375210 TI - Steroid dependency and trends in prescribing for inflammatory bowel disease - a 20-year national population-based study. AB - BACKGROUND: It is unclear whether adherence to prescribing standards has been achieved in inflammatory bowel disease (IBD). AIM: To determine how prescribing of 5-aminosalicylates (5-ASAs), steroids and thiopurines has changed in response to emerging evidence. METHODS: We examined trends in oral and topical therapies in 23 509 incident IBD cases (6997 with Crohn's disease and 16 512 with ulcerative colitis) using a nationally representative sample between 1990 and 2010. We created five eras according to the year of diagnosis: era 1 (1990-1993), era 2 (1994-1997), era 3 (1998-2001), era 4 (2002-2005) and era 5 (2006-2010). We calculated the proportion of patients treated with prolonged 5-ASAs (>12 months) and steroid dependency, defined as prolonged steroids (>3 months) or recurrent (restarting within 3 months) steroid exposure. We calculated the cumulative probability of receiving each medication using survival analysis. RESULTS: Half of the Crohn's disease patients were prescribed prolonged oral 5-ASAs during the study, although this decreased between era 3 and 5 from 61.8% to 56.4% (P = 0.002). Thiopurine use increased from 14.0% to 47.1% (P < 0.001) between era 1 and 5. This coincided with a decrease in steroid dependency from 36.5% to 26.8% (P < 0.001) between era 1 and 2 and era 4 and 5 respectively. In ulcerative colitis, 49% of patients were maintained on prolonged oral 5-ASAs. Despite increasing thiopurine use, repeated steroid exposure increased from 15.3% to 17.8% (P = 0.02) between era 1 and 2 and era 4 and 5 respectively. CONCLUSIONS: Prescribing in clinical practice insufficiently mirrors the evidence base. Physicians should direct management towards reducing steroid dependency and optimising 5-ASA use in patients with IBD. PMID- 27375211 TI - The centenary of the discovery of trench fever, an emerging infectious disease of World War 1. AB - In 1915, a British medical officer on the Western Front reported on a soldier with relapsing fever, headache, dizziness, lumbago, and shin pain. Within months, additional cases were described, mostly in frontline troops, and the new disease was called trench fever. More than 1 million troops were infected with trench fever during World War 1, with each affected soldier unfit for duty for more than 60 days. Diagnosis was challenging, because there were no pathognomonic signs and symptoms and the causative organism could not be cultured. For 3 years, the transmission and cause of trench fever were hotly debated. In 1918, two commissions identified that the disease was louse-borne. The bacterium Rickettsia quintana was consistently found in the gut and faeces of lice that had fed on patients with trench fever and its causative role was accepted in the 1920s. The organism was cultured in the 1960s and reclassified as Bartonella quintana; it was also found to cause endocarditis, peliosis hepatis, and bacillary angiomatosis. Subsequently, B quintana infection has been identified in new populations in the Andes, in homeless people in urban areas, and in individuals with HIV. The story of trench fever shows how war can lead to the recrudescence of an infectious disease and how medicine approached an emerging infection a century ago. PMID- 27375212 TI - Harmonisation in study design and outcomes in paediatric antibiotic clinical trials: a systematic review. AB - There is no global consensus on the conduct of clinical trials in children and neonates with complicated clinical infection syndromes. No comprehensive regulatory guidance exists for the design of antibiotic clinical trials in neonates and children. We did a systematic review of antibiotic clinical trials in complicated clinical infection syndromes (including bloodstream infections and community-acquired pneumonia) in children and neonates (0-18 years) to assess whether standardised European Medicines Agency (EMA) and US Food and Drug Administration (FDA) guidance for adults was used in paediatrics, and whether paediatric clinical trials applied consistent definitions for eligibility and outcomes. We searched MEDLINE, Cochrane CENTRAL databases, and ClinicalTrials.gov between Jan 1, 2000, and Nov 18, 2015. 82 individual studies met our inclusion criteria. The published studies reported on an average of 66% of CONSORT items. Study design, inclusion and exclusion criteria, and endpoints varied substantially across included studies. The comparison between paediatric clinical trials and adult EMA and FDA guidance highlighted that regulatory definitions are only variably applicable and used at present. Absence of consensus for paediatric antibiotic clinical trials is a major barrier to harmonisation in research and translation into clinical practice. To improve comparison of therapies and strategies, international collaboration among all relevant stakeholders leading to harmonised case definitions and outcome measures is needed. PMID- 27375213 TI - Morphology and ultrastructure of Brachymystax lenok tsinlingensis spermatozoa by scanning and transmission electron microscopy. AB - This study was conducted to investigate Brachymystax lenok tsinlingensis spermatozoa cell morphology and ultrastructure through scanning and transmission electron microscopy. Findings revealed that the spermatozoa can be differentiated into three major parts: a spherical head without an acrosome, a short mid-piece, and a long, cylindrical flagellum. The mean length of the spermatozoa was 36.11+/ 2.84MUm, with a spherical head length of 2.78+/-0.31MUm. The mean anterior and posterior head widths were 2.20+/-0.42MUm and 2.55+/-0.53MUm, respectively. The nuclear fossa was positioned at the base of the nucleus that contained the anterior portion of flagellum and a centriolar complex (proximal and distal centrioles). The short mid-piece was located laterally to the nucleus and possessed just one spherical mitochondrion with a mean diameter of 0.65+/ 0.14MUm. The spermatozoa flagellum was long and cylindrical, and could be separated into two parts: a long main-piece and a short end-piece. The main piece of the flagellum had short irregular side-fins. The axoneme composed the typical '9+2' microtubular doublet structure and was enclosed by the cell membran e. This study confirmed that B. lenok tsinlingensis spermatozoa can be categorized as teleostean "Type I" spermatozoa; 'primitive' or 'ect-aquasperm type' spermatozoa. To the best of the authers knowledge, this was the first study conducted on the morphology and ultrastructure of B. lenok tsinlingensis spermatozoa. PMID- 27375214 TI - Trends in the sand: Directional evolution in the shell shape of recessing scallops (Bivalvia: Pectinidae). AB - Directional evolution is one of the most compelling evolutionary patterns observed in macroevolution. Yet, despite its importance, detecting such trends in multivariate data remains a challenge. In this study, we evaluate multivariate evolution of shell shape in 93 bivalved scallop species, combining geometric morphometrics and phylogenetic comparative methods. Phylomorphospace visualization described the history of morphological diversification in the group; revealing that taxa with a recessing life habit were the most distinctive in shell shape, and appeared to display a directional trend. To evaluate this hypothesis empirically, we extended existing methods by characterizing the mean directional evolution in phylomorphospace for recessing scallops. We then compared this pattern to what was expected under several alternative evolutionary scenarios using phylogenetic simulations. The observed pattern did not fall within the distribution obtained under multivariate Brownian motion, enabling us to reject this evolutionary scenario. By contrast, the observed pattern was more similar to, and fell within, the distribution obtained from simulations using Brownian motion combined with a directional trend. Thus, the observed data are consistent with a pattern of directional evolution for this lineage of recessing scallops. We discuss this putative directional evolutionary trend in terms of its potential adaptive role in exploiting novel habitats. PMID- 27375215 TI - Nanotoxicological study of polyol-made cobalt-zinc ferrite nanoparticles in rabbit. AB - The increasing use of engineered nanomaterials in commercial manufacturing and consumer products presents an important toxicological concern. Superparamagnetic zinc-cobalt ferrite nanoparticles (SFN) emerge as a promising tool for early cancer diagnostics and targeted therapy. However, toxicity and biological activities of SFN should be evaluated in vitro and in vivo in animal before any clinical application. In this study we aim to synthesize and characterize such objects using polyol process in order to assess its nanotoxicological profile in vitro as well as in vivo. The produced particles consist of a cobalt-zinc ferrite phase corresponding to the Zn0.8Co0.2Fe2O4 composition. They are isotropic in shape single crystals of 8nm in size. The thermal variation of their dc magnetization confirms their superparamagnetic behavior. In vitro, acute exposure (4h) to them (100MUgmL(-1)) induced an important decrease of healthy Human Umbilical Vein Endothelial Cells (HUVECs) viability. In vivo investigation in New Zealand rabbits revealed that they lead to tissue toxicities; in lungs, liver and kidneys. Our investigations report, for the first time as far as we know, that SFN exhibit harmful properties in human cells and mammals. PMID- 27375216 TI - Thymoquinone effectively alleviates lung fibrosis induced by paraquat herbicide through down-regulation of pro-fibrotic genes and inhibition of oxidative stress. AB - The potential preventive and therapeutic effects of thymoquinone (TQ) and its molecular mechanism were evaluated in paraquat (PQ)-induced pulmonary fibrosis in mice. TQ was administered orally at the doses of 20 and 40mg/kg during the course and after development of fibrosis. Pathological changes, expressions of genes involved in fibrogenesis, hydroxyproline (HP) and oxidative stress parameters were determined in the lung tissues. TQ dose-dependently recovered the pathological changes induced by PQ. TQ decreased hydroxyproline content, lipid peroxidation and restored the antioxidant enzymes to the normal values. In molecular level, expressions of TGF-beta1, alpha-SMA, collagen 1a1 and collagen 4a1 genes were also returned to the control level by TQ. This study indicated that TQ has the preventive and therapeutic potentials for the treatment of lung fibrosis by inhibition of oxidative stress and down-regulation of profibrotic genes. PMID- 27375217 TI - Clustering DNA sequences using the out-of-place measure with reduced n-grams. AB - The alignment-free n-gram based method with the out-of-place measures as the distance has been successfully applied to automatic text or natural languages categorization in real time. However, it is not clear about its performance and the selection of n for comparing genome sequences. Here we propose a symmetric version of the out-of-place measure and a new approach for finding the optimal range of n to construct a phylogenetic tree with the symmetric out-of-place measures. Our method is then applied to real genome sequence datasets. The resulting phylogenetic trees are matching with the standard biological classification. It shows that our proposed method is a very powerful tool for phylogenetic analysis in terms of both classification accuracy and computation efficiency. PMID- 27375218 TI - Protein sequence analysis by incorporating modified chaos game and physicochemical properties into Chou's general pseudo amino acid composition. AB - In this contribution we introduced a novel graphical method to compare protein sequences. By mapping a protein sequence into 3D space based on codons and physicochemical properties of 20 amino acids, we are able to get a unique P vector from the 3D curve. This approach is consistent with wobble theory of amino acids. We compute the distance between sequences by their P-vectors to measure similarities/dissimilarities among protein sequences. Finally, we use our method to analyze four datasets and get better results compared with previous approaches. PMID- 27375220 TI - The pre-spawning migratory behaviour of Atlantic salmon Salmo salar in a large lacustrine catchment. AB - The movements of adult Atlantic salmon Salmo salar were determined as they migrated to spawning habitats in a large lacustrine catchment, Lough Neagh, in Northern Ireland. The minimum average ground speed of S. salar through the lake was 2.1 km day(-1) and the mean residence time was 11 days. Tagged S. salar tended to actively migrate through the lake which represented a transitory habitat for adult S. salar. Migration time from the release site, through the lake, to a spawning tributary decreased during the migratory period. During the 4 year study period between 20.5 and 41.6% of tagged S. salar which entered the lake each year, explored at least one other channel before ascending the final spawning tributary. Exploratory behaviour was more likely in S. salar which spawned in the tributaries furthest from the sea. Exploratory behaviour was also more likely to occur during periods of reduced discharge in the natal stream. The fishery management implications of complex pre-spawning behaviour in a mixed stock lacustrine system, are discussed. PMID- 27375219 TI - Mutations Causing Slow-Channel Myasthenia Reveal That a Valine Ring in the Channel Pore of Muscle AChR is Optimized for Stabilizing Channel Gating. AB - We identify two novel mutations in acetylcholine receptor (AChR) causing a slow channel congenital myasthenia syndrome (CMS) in three unrelated patients (Pts). Pt 1 harbors a heterozygous betaV266A mutation (p.Val289Ala) in the second transmembrane domain (M2) of the AChR beta subunit (CHRNB1). Pts 2 and 3 carry the same mutation at an equivalent site in the epsilon subunit (CHRNE), epsilonV265A (p.Val285Ala). The mutant residues are conserved across all AChR subunits of all species and are components of a valine ring in the channel pore, which is positioned four residues above the leucine ring. Both betaV266A and epsilonV265A reduce the amino acid size and lengthen the channel opening bursts by fourfold by enhancing gating efficiency by approximately 30-fold. Substitution of alanine for valine at the corresponding position in the delta and alpha subunit prolongs the burst duration four- and eightfold, respectively. Replacing valine at epsilon codon 265 either by a still smaller glycine or by a larger leucine also lengthens the burst duration. Our analysis reveals that each valine in the valine ring contributes to channel kinetics equally, and the valine ring has been optimized in the course of evolution to govern channel gating. PMID- 27375221 TI - Direct Cross-Couplings of Propargylic Diols. AB - [Pd(PPh3 )4 ] catalyzes a Suzuki-Miyaura-like twofold cross-coupling sequence between underivatized propargylic diols and either aryl or alkenyl boronic acids to furnish highly substituted 1,3-dienes. Thus, 2,3-diaryl-1,3-butadienes and their dialkenic congeners ([4]dendralenes) are delivered in a (pseudo)halogen free, single-step synthesis which supersedes existing methods. Allenols are also readily formed. Treatment of these single- and twofold cross-coupled products with acid leads to remarkably short syntheses of highly-substituted benzofulvenes and aryl indenes, respectively. PMID- 27375222 TI - Facile preparation of aqueous suspensions of WO3/sulfonated PEDOT hybrid nanoparticles for electrochromic applications. AB - An aqueous suspension of WO3/poly(4-(2,3-dihydrothieno[3,4-b]-[1,4]dioxin-2-yl methoxy)-1-butanesulfonic acid) (PEDTS) hybrid nanoparticles (NPs) is prepared by air-assisted oxidative polymerization and simultaneous attachment of PEDTS on WO3 NPs, and used for electrochromic (EC) film fabrication via air-brush spraying. The hybrid EC device exhibits enhanced EC properties compared to the ones based on WO3-NP or PEDTS alone. PMID- 27375223 TI - Update on Post-mastectomy Lymphedema Management. AB - Lymphedema is a chronic, progressive condition caused by an imbalance of lymphatic flow. Upper extremity lymphedema has been reported in 16-40% of breast cancer patients following axillary lymph node dissection. Furthermore, lymphedema following sentinel lymph node biopsy alone has been reported in 3.5% of patients. While the disease process is not new, there has been significant progress in the surgical care of lymphedema that can offer alternatives and improvements in management. The purpose of this review is to provide a comprehensive update and overview of the current advances and surgical treatment options for upper extremity lymphedema. PMID- 27375224 TI - Nightshade Wound Secretion: The World's Simplest Extrafloral Nectar? AB - Wounded nightshade leaves secrete a sugary liquid that, like extrafloral nectar (EFN), attracts ants as defence against herbivores. The secretion of these droplets requires no detectable nectary tissue, showing how little it takes to produce a functioning nectary. Easy de novo formation of extrafloral nectaries explains their 'scattered' phylogenetic distribution. PMID- 27375226 TI - Cell-cell fusion in the nervous system: Alternative mechanisms of development, injury, and repair. AB - Over a century ago, the seminal work of Ramon y Cajal revealed that the nervous system is made of individual units, the neurons, which are related to each other by contiguity rather than continuity. This view overturned the idea that the nervous system was a reticulum of fibers, a rete diffusa nervosa, as proposed and defined by Camillo Golgi. Although the neuron theory has been widely confirmed in every model system studied and constitutes the basis of modern neuroscience, evidence accumulated over the years suggests that neurons, similar to other types of cells, have the potential to fuse their membranes and undergo cell-cell fusion under certain conditions. This concept adds a substantial layer to our view of the nervous system and how it functions. Here, we bring together past and more recent discoveries on multiple aspects of neuronal fusion, discussing how this cellular event is generated, and what consequences it has for our understanding of nervous system development, disease, injury, and repair. PMID- 27375225 TI - Expression of dynein, cytoplasmic 2, heavy chain 1 (DHC2) associated with glioblastoma cell resistance to temozolomide. AB - Temozolomide (TMZ) is the main chemotherapeutic drug utilized for the treatment of glioblastoma multiforme (GMB), however, drug resistance often leads to tumor recurrence and poor outcomes. GMB cell lines were treated with TMZ for up to two weeks and then subjected to proteomics analysis to identify the underlying molecular pathology that is associated with TMZ resistance. Proteomics data showed that TMZ altered expression of proteins that related to cytoskeleton structure and function, such as DHC2 and KIF2B. qRT-PCR and immunofluorescence were used to verify expression of DHC2 and KIF2B in these cells. Immunohistochemistry was used to verify expression of these two proteins in xenografts of a nude mouse model, and ex vivo GBM tissue samples. Their expression was knocked down using siRNA to confirm their role in the regulation of GBM cell sensitivity to TMZ. Knockdown of DHC2 expression enhanced sensitivity of U87 cells to TMZ treatment. Ex vivo data showed that DHC2 expression in GBM tissue samples was associated with tumor recurrence after TMZ chemotherapy. These results indicated cytoskeleton related protein DHC2 reduced sensitivity of GBM cells to TMZ treatment. Further studies should assess DHC2 as a novel target in GBM for TMZ combination treatment. PMID- 27375227 TI - Peromyscus as a model of human disease. AB - Animals of the genus Peromyscus have been a particularly informative model for many areas of study, including behavior, evolution, anatomy, physiology and genetics. While their use in modeling human disease and pathology has been relatively restricted, certain qualities of Peromyscine mice may make them a good candidate for such studies. Pathophysiological conditions where Peromyscus may be of particular value involve aging, reactive oxygen species-associated pathologies, metabolism and detoxification, diabetes, and certain cancers. In this review article we will summarize pathological conditions where Peromyscus have been used effectively, we will discuss factors limiting the use of Peromyscus in studying pathology and we will indicate areas at which the use of this model may be of special value. PMID- 27375228 TI - Childhood medulloblastoma. AB - Medulloblastoma accounts for 15-20% of childhood nervous system tumours. The risk of dying was reduced by 30% in the last twenty years. Patients are divided in risk strata according to post-surgical disease, dissemination, histology and some molecular features such as WNT subgroup and MYC status. Sixty to 70% of patients older than 3 years are assigned to the average-risk group. High-risk patients include those with disseminated and/or residual disease, large cell and/or anaplastic histotypes, MYC genes amplification. Current and currently planned clinical trials will: (1) evaluate the feasibility of reducing both the dose of craniospinal irradiation and the volume of the posterior fossa radiotherapy (RT) for those patients at low biologic risk, commonly identified as those having a medulloblastoma of the WNT subgroup; (2) determine whether intensification of chemotherapy (CT) or irradiation can improve outcome in patients with high-risk disease; (3) find target therapies allowing tailored therapies especially for relapsing patients and those with higher biological risk. PMID- 27375229 TI - Toxicity, bio-distribution and metabolism of CO-releasing molecules based on cobalt. AB - CO-releasing molecules (CORMs) containing [Co2(CO)6] moiety show many bioactivities, such as anti-inflammatory and antitumor cell proliferation. However, so far, no one knows their properties in vivo. So, here, we evaluated some these kind CORMs from drug-like properties including cytotoxicity, toxicity in vivo, distribution and metabolism. The results show all the tested complexes displayed antiproliferative activity to HeLa cell and HepG2 cell lines, and their IC50 values were 36-110uM against HeLa cells and 39-140uM against HepG2 cells. Toxicity tests of mice, we used oral acute toxic class method and got their LD50 values; among them, LD50 of complex 1 and complex 4 were in 2500-5000mgkg(-1) and complex 7 over 5000mgkg(-1). The developmental toxicities of the complexes were investigated in embryonic zebrafish. The mortality, hatch rate, malformation, heart rate, spontaneous movement, and larval behavior were examined, and we found both complexes 4 and 7 have not toxicity at low concentration (<1.0MUM) but have higher toxicity at high concentration (>5.0MUM). After several consecutive i.p administrations, tested complexes severely damaged rat liver and kidney in both functional and morphological aspects. Through metal ion measurement using ICP AES, we found the tested complexes were unevenly distributed in tissues and organs; complex 4 has a big prone to collect in liver, whereas complex 7 easily enters to kidney. After administration 480min later, most of complex 7 excreted from kidney and entered urine, while complex 4 needed 9h at least. This results show cobalt did not accumulate, and could excrete with the urine. In vivo, Co(0) in complexes was oxidised to Co(II). In addition, the substituents significantly affected the rate of CO-release, cytotoxicity and their bio-distribution. In the view of these aspects, the CORMs based cobalt has a potential property to be a medicine. PMID- 27375230 TI - Critical time for neovascularization/angiogenesis to allow free flap survival after delayed postoperative anastomotic compromise without surgical intervention: A review of the literature. AB - BACKGROUND: The aim of this study is to determine the minimal postoperative time required that may allow free flap survival after occlusion or ligation of the microsurgical anastomosis without surgical intervention. METHODS: All reports describing free flap survival and failure after delayed postoperative vascular compromise (after postoperative day 3); including thrombosis and ligation, without revision of the microsurgical anastomoses were reviewed. The type of flap, recipient site, vessel of occlusion, postoperative compromise day, and nonsurgical treatment were analyzed. RESULTS: 22 reports (32 flaps) detailed 16 arterial, 6 venous, and 10 simultaneously arterial and venous (vascular pedicle) compromise in 16 head and neck, 10 lower extremity, 4 breast, and 2 upper extremity free tissue transfers. 12 flaps survived without any intervention, 6 survived with conservative therapy (anticoagulation or leeches), and 14 survived despite pedicle ligation. The range of critical day of occlusion did not differ significantly among vessel types. 75% of arterial compromise occurred between 6 and 15 days. 75% of vascular pedicle compromise occurred between 8.5 and 18 days. When compared to jejunal flaps, skin flaps survived after earlier postoperative occlusion (10.2 vs. 20.8 days; P = 0.01). CONCLUSION: This analysis suggests that free flaps compromised by vascular thrombosis or pedicle ligation may survive with only conservative therapy when the event occurs after a minimal critical time period. Flap survival is more probable when arterial occlusion or pedicle ligation occurs after postoperative day 12, but this minimal critical period may be as low as 6 days for arterial occlusion. (c) 2016 Wiley Periodicals, Inc. Microsurgery 36:604-612, 2016. PMID- 27375231 TI - Baseline HBsAg and HBcrAg titres allow peginterferon-based 'precision medicine' in HBeAg-negative chronic hepatitis B patients. AB - Quantitative hepatitis B core-related antigen (qHBcrAg) has been proposed as an additional marker to quantitative HBsAg (qHBsAg), for management of chronic hepatitis B. Evaluate baseline combination of qHBsAg and qHBcrAg for identification of patients that could benefit from pegylated interferon-alpha-2a (PegIFN)-based therapy. Sixty-two HBeAg-negative patients treated with PegIFN or PegIFN plus tenofovir disoproxil fumarate (PegIFN+TDF). HBsAg and HBcrAg titres were evaluated at baseline. Thirty patients received PegIFN and 32 PegIFN+TDF. SR was 10 of 30 and 17 of 32 in PegIFN and PegIFN+TDF patients, respectively. Cut offs determined by maximized Youden's index for identifying patients likely to respond to therapy were as follows: 3.141 log10 IU/mL and 3.450 log10 U/mL for HBsAg and HBcrAg, respectively. At the end of 3 years post-treatment follow-up, HBsAg loss was observed in 7 of 30 and 6 of 32 in PegIFN and PegIFN+TDF patients, respectively. The AUC was estimated to be 0.716 (95% CI [0.578, 0.855]) for HBsAg and 0.668 (95% CI [0.524, 0.811]) for HBcrAg (P=.5541). PPVs for AUCs(95%CI) were 0.762(0.590-0.947), 0.714(0.533-1.000) and 0.800(0.611-1.000), and NPVs for AUCs(95%CI) were 0.756(0.660-0.899), 0.718(0.630-0.857) and 0.765(0.675-0.889) for qHBsAg, qHBcrAg and the combination of both markers, respectively. Baseline qHBsAg 3.141 log10 IU/mL and qHBcrAg 3.450 log10 U/mL thresholds used separately or in combination allow prediction of response, prior to PegIFN-based therapy, with a PPV of 80.3% and NPV of 76.5%. Baseline qHBsAg is predictive of HBsAg loss. Both markers could be used, separately or in combination, for PegIFN-based 'precision therapy'. Our results emphasize that the combination of PegIFN alpha 2a plus TDF with 53% of SR might be an alternative to finite therapy. PMID- 27375232 TI - Submitral aneurysm in children. AB - BACKGROUND: We report a surgical series of submitral aneurysm in children. METHODS: Between March 2011 and December 2015, eight consecutive patients less than 18 years old with submitral aneurysm underwent surgical correction. RESULTS: Six patients were female, the mean age was 7 +/- 3.8 years old, and mean weight was 21.4 kg. Six patients were in NYHA functional class III or IV. Six patients underwent repair via a transatrial approach, another with a transatrial combined with transaneurysmal approach, and another with a transventricular approach. There were no in-hospital deaths but one 30-day mortality. One patient required reoperation. Two patients required mitral valve replacement. At discharge, one patient had severe and another had moderate mitral regurgitation. The mean follow up time was 26.4 months and five patients were alive. No reintervention was required. CONCLUSIONS: Submitral aneurysm is not restricted to adults. Heart failure is the commonest clinical presentation in the pediatric age. The transatrial approach is feasible, safe, and associated with good short-term results. The mitral valve can be preserved in the majority of cases. PMID- 27375233 TI - Single and combined genotoxicity effects of six pollutants on THP-1 cells. AB - The objective of this study was to evaluate the single and combined genotoxic effects of six food pollutants (Chrysoidine G, Sudan I, acid orange II, malachite green, acrylamide, and potassium bromate) on THP-1 cells through comet assay. The results of the single tests indicated that the pollutants increased the percentage of tail DNA (% tail DNA) in a dose-dependent manner. Moreover, the % tail DNA values induced by synthetic colorants (Chrysoidine G, Sudan I, acid orange II, and malachite green) were significantly higher than those by acrylamide or potassium bromate at most concentrations. In the combined tests, Chrysoidine G (422 MUmol/L) or acrylamide (400 MUmol/L) was mixed with different concentrations of the other five pollutants respectively. In the first combined tests, most mixtures significantly increased the % tail DNA values with the exception of Chrysoidine G and acid orange II. In the second tests, there were no significant differences in the % tail DNA values between the single and combined tests at most cases. PMID- 27375234 TI - SETD5 loss-of-function mutation as a likely cause of a familial syndromic intellectual disability with variable phenotypic expression. AB - Loss-of-function de novo mutations in the SETD5 gene, encoding a putative methyltransferase, are an important cause of moderate/severe intellectual disability as evidenced by the results of sequencing large patient cohorts. We present the first familial case of a SETD5 mutation contributing to a phenotype of congenital heart defects and dysmorphic features, with variable expression, in two siblings and their father. Interestingly, the father demonstrated only mild intellectual impairment. Family based exome sequencing combined to careful parental phenotyping may reveal a more complex clinical picture in newly recognized syndromes. (c) 2016 Wiley Periodicals, Inc. PMID- 27375235 TI - A chaotic self-oscillating sunlight-driven polymer actuator. AB - Nature provides much inspiration for the design of materials capable of motion upon exposure to external stimuli, and many examples of such active systems have been created in the laboratory. However, to achieve continuous motion driven by an unchanging, constant stimulus has proven extremely challenging. Here we describe a liquid crystalline polymer film doped with a visible light responsive fluorinated azobenzene capable of continuous chaotic oscillatory motion when exposed to ambient sunlight in air. The presence of simultaneous illumination by blue and green light is necessary for the oscillating behaviour to occur, suggesting that the dynamics of continuous forward and backward switching are causing the observed effect. Our work constitutes an important step towards the realization of autonomous, persistently self-propelling machines and self cleaning surfaces powered by sunlight. PMID- 27375236 TI - Differentiation of adipose stem cells seeded towards annulus fibrosus cells on a designed poly(trimethylene carbonate) scaffold prepared by stereolithography. AB - Cell-based therapies could potentially restore the biomechanical function and enhance the self-repair capacity of annulus fibrosus (AF) tissue. However, choosing a suitable cell source and scaffold design are still key challenges. In this study, we assessed the in vitro ability of human adipose stem cells (hASCs), an easily available cell source to produce AF-like matrix in novel AF-mimetic designed scaffolds based on poly(trimethylene carbonate) and built by stereolithography. To facilitate efficient differentiation of hASCs towards AF tissue, we tested different culture medium compositions and cell seeding techniques. This is the first study to report that medium supplementation with transforming growth factor (TGF)-beta3 is essential to support AF differentiation of hASCs while TGF-beta1 has negligible effect after 21 days of culture. Fibrin gel seeding resulted in superior cell distribution, proliferation and AF-like matrix production of hASCs compared to direct and micromass seeding under TGF beta3 stimulation. Not only the production of sulphated glycosaminoglycans (sGAG) and collagen was significantly upregulated, but the formed collagen was also oriented and aligned into bundles within the designed pore channels. The differentiated hASCs seeded with fibrin gel were also found to have a comparable sGAG:collagen ratio and gene expression profile as native AF cells demonstrating the high potential of this strategy in AF repair. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27375237 TI - Tunable Lipidoid-Telodendrimer Hybrid Nanoparticles for Intracellular Protein Delivery in Brain Tumor Treatment. AB - A strategy to precisely engineer lipidoid-telodendrimer binary hybrid nanoparticles that offer enhanced cell membrane permeability for therapeutic proteins to reach the intracellular targets is established. The highly controllable biochemical and physical properties of the nanoparticles make them promising for protein-based brain cancer treatment with the assistance of convection-enhanced delivery. PMID- 27375238 TI - Multidrug-resistant and epidemic clones of Escherichia coli from natural beds of Venus clam. AB - Epidemic Escherichia coli clones have been recovered in marine sediment along the coast of Marche, an Adriatic region in central Italy. In the present study, E. coli strains from the clam Chamelea gallina, sampled from seven natural beds in the same area, were detected. Selected E. coli isolates from all sampling sites were screened for antimicrobial susceptibility, genetic diversity and correlation. The majority (60%) belonged to phylogroups A or B1, 31% to the other groups (B2, C, D, E, F), 8% to cryptic clades, and 1% were untypable. Moreover, 33.3% of isolates were resistant to at least one drug and 11% were multidrug resistant (MDR). The most common resistance was to tetracycline, ampicillin, and streptomycin. No clonality was detected, but the strains' high genetic heterogeneity pointed at multiple sources of microbiological contamination. MLST analysis found potentially pathogenic and even epidemic MDR strains in clams collected in class A (ST746 and ST46) and class B (ST393, ST58 and ST131) areas, indicating that strains of clinical origin are detectable in clams. These data highlight that eating raw or lightly cooked clams may pose a health risk if purification is not performed or is ineffective. PMID- 27375240 TI - Influence of Lactobacillus plantarum WCFS1 on post-acidification, metabolite formation and survival of starter bacteria in set-yoghurt. AB - The objectives of this study were to evaluate the growth and survival of the model probiotic strain Lactobacillus plantarum WCFS1 in co-culture with traditional yoghurt starters and to investigate the impact of preculturing on their survival and metabolite formation in set-yoghurt. L. plantarum WCFS1 was precultured under sublethal stress conditions (combinations of elevated NaCl and low pH) in a batch fermentor before inoculation in milk. Adaptive responses of L. plantarum WCFS1 were evaluated by monitoring bacterial population dynamics, milk acidification and changes in volatile and non-volatile metabolite profiles of set yoghurt. The results demonstrated that sublethal preculturing did not significantly affect survival of L. plantarum WCFS1. On the other hand, incorporation of sublethally precultured L. plantarum WCFS1 significantly impaired the survival of Lactobacillus delbrueckii subsp. bulgaricus which consequently reduced the post-acidification of yoghurt during refrigerated storage. A complementary metabolomics approach using headspace SPME-GC/MS and (1)H NMR combined with multivariate statistical analysis revealed substantial impact of sublethally precultured L. plantarum WCFS1 on the metabolite profiles of set-yoghurt. This study provides insight in the technological implications of non-dairy model probiotic strain L. plantarum WCFS1, such as its good stability in fermented milk and the inhibitory effect on post-acidification. PMID- 27375239 TI - Potential for transfer of Escherichia coli O157:H7, Listeria monocytogenes and Salmonella Senftenberg from contaminated food waste derived compost and anaerobic digestate liquid to lettuce plants. AB - The diversion of food wastes from landfill to sustainable disposal methods, such as composting and anaerobic digestion, has led to an increase in the soil amendment products that are now commercially available and which are derived from both of these processes. The use of such products as soil amendments during the production of ready-to-eat (RTE) crops is increasing worldwide. The aim of this study was to investigate the potential of three well-recognised bacterial pathogens of importance to public health, namely Escherichia coli O157:H7, Salmonella Senftenberg and Listeria monocytogenes, to become internalised in lettuce plants from peat growing media amended with contaminated food waste derived compost and anaerobic digestion liquid. The results demonstrated both S. Senftenberg and E. coli O157:H7 are capable of internalisation at lower inoculation levels, compared to previous studies. The internalisation was visualised through confocal microscopy. Internalisation of L. monocytogenes did not occur, however significant levels of L. monocytogenes contamination occurred on the non-sterilised plant surface. Assessing the internalisation potential for each of these pathogens, through the compost and anaerobic digestate matrices, allows for better risk assessment of the use of these products in a horticultural setting. PMID- 27375241 TI - Chitosan boosts the antimicrobial activity of Origanum vulgare essential oil in modified atmosphere packaged pork. AB - The potential of chitosan as a possible booster of the antimicrobial activity of Origanum vulgare EO (OEO) against spoilage bacteria and Listeria monocytogenes was investigated in fresh pork meat. Pork fillets were inoculated with 3 L. monocytogenes strains, dipped either in Origanum vulgare (oregano) Essential Oil (OEO) at 2 and 4%, or in chitosan 1% alone or added with 2 and 4% OEO, then packed under modified atmosphere (70% O2, 20% CO2, 10% N2) and stored at 4 degrees C for 15 days. OEO did not reduce L. monocytogenes growth, while 2 Log decrease was obtained after 2 days of storage in treatments with chitosan alone or with OEO, with growth inhibition up to day 15 in samples with chitosan and OEO 4%. When OEO was combined with chitosan, total viable counts and spoilage bacteria were reduced and contained over time, particularly Pseudomonas (2.0 Log CFU/g at day 15) and Brochothrix thermosphacta (undetectable). All the treatments applied extended meat shelf-life with respect to control, whose commercial shelf life was 10 days. Chitosan treatments enhanced L* and maintained a* values almost stable during storage. Chitosan and OEO singly applied reduced lipid oxidation (0.62-0.75 mg malondialdehyde/Kg meat) compared to control (0.99 mg malondialdehyde/Kg meat). Finally, chitosan treated samples were not recognized with respect to the control, whereas OEO gave bitter taste; chitosan with OEO instead mitigated the effect of OEO addition to meat. Chitosan combined with OEO boosts its antimicrobial activity and shows a potential for application in industrial production of fresh pork in MAP, to achieve shelf-life extension, control of L. monocytogenes growth, stability of color and protective effect from oxidation, with low sensory impact. PMID- 27375242 TI - Variable tellurite resistance profiles of clinically-relevant Shiga toxin producing Escherichia coli (STEC) influence their recovery from foodstuffs. AB - Tellurite (Tel)-amended selective media and resistance (Tel-R) are widely used for detecting Shiga toxin-producing Escherichia coli (STEC) from foodstuffs. Tel R of 81 O157 and non-O157 STEC strains isolated from animal, food and human was thus investigated. Variations of STEC tellurite minimal inhibitory concentration (MIC) values have been observed and suggest a multifactorial and variable tellurite resistome between strains. Some clinically-relevant STEC were found highly susceptible and could not be recovered using a tellurite-based detection scheme. The ter operon was highly prevalent among highly Tel-R STEC but was not always detected among intermediately-resistant strains. Many STEC serogroup strains were found to harbor sublines showing a gradient of MIC values. These Tel R sublines showed statistically significant log negative correlations with increasing tellurite concentration. Whatever the tellurite concentration, the highest number of resistant sublines was observed for STEC belonging to the O26 serogroup. Variations in the number of these Tel-R sublines could explain the poor recovery of some STEC serogroups on tellurite-amended media especially from food products with low levels of contamination. Comparison of tellurite MIC values and distribution of virulence-related genes showed Tel-R and virulence to be related. PMID- 27375243 TI - Industrial application of selected lactic acid bacteria isolated from local semolinas for typical sourdough bread production. AB - Four obligate heterofermentative lactic acid bacteria (LAB) strains (Weissella cibaria PON10030 and PON10032 and Leuconostoc citreum PON 10079 and PON10080) were tested as single strain starters, mono-species dual strain starters, and multiple strain starter for the preparation and propagation of sourdoughs for the production of a typical bread at industrial level. The kinetics of pH and TTA during the daily sourdough refreshments indicated a correct acidification process for all trials. The concentration of lactic and acetic acid increased consistently during fermentation. The resulting molar ratios between these two organic acids in the experimental trials were lower than those observed in the control trial. The microbiological investigation showed levels of approximately 10(9) CFU/mL in almost all sourdoughs and the comparison of the genetic polymorphisms of the dominating LAB with those of the pure cultures evidenced the persistence of the added strains over time. The resulting breads were evaluated for several quality parameters. The breads with the greatest height were obtained with the quadruple combination of leuconostocs and weissellas. The highest softness was registered for the breads obtained from fermentations performed by W. cibaria PON10032 alone and in combination. The different inocula influenced also the color, the void fraction, the cell density and the mean cell area of the breads. Different levels of acids, alcohols, aldehydes, esters, hydrocarbons, ketones, terpenes, furans and phenol were emitted by the breads. The sensory tests indicated the breads from the sourdoughs fermented with the seven LAB inocula as sweeter and less acidic than control breads and the breads from the trials with the highest complexity of LAB inoculums were those more appreciated by tasters. A multivariate approach found strong differences among the trials. In particular, control breads and the breads obtained with different starter LAB were quite distant and a more strict relation was found among the productions carried out by W. cibaria strains. This study proved the suitability of the selected strains of L. citreum and W. cibaria for industrial-scale level applications in sourdough bread production. PMID- 27375244 TI - The spxB gene as a target to identify Lactobacillus casei group species in cheese. AB - This study focused on the spxB gene, which encodes for pyruvate oxidase. The presence of spxB in the genome and its transcription could be a way to produce energy and allow bacterial growth during carbohydrate starvation. In addition, the activity of pyruvate oxidase, which produces hydrogen peroxide, could be a mechanism for interspecies competition. Because this gene seems to provide advantages for the encoding species for adaptation in complex ecosystems, we studied spxB in a large set of cheese isolates belonging to the Lactobacillus casei group. Through this study, we demonstrated that this gene is widely found in the genomes of members of the L. casei group and shows variability useful for taxonomic studies. In particular, the HRM analysis method allowed for a specific discrimination between Lactobacillus rhamnosus, Lactobacillus paracasei and L. casei. Regarding the coding region, the spxB functionality in cheese was shown for the first time by real-time PCR, and by exploiting the heterogeneity between the L. casei group species, we identified the bacterial communities encoding the spxB gene in this ecosystem. This study allowed for monitoring of the active bacterial community involved in different stages of ripening by following the POX pathway. PMID- 27375245 TI - A large factory-scale application of selected autochthonous lactic acid bacteria for PDO Pecorino Siciliano cheese production. AB - The main hypothesis of this study was that the autochthonous lactic acid bacteria (LAB) selected for their dairy traits are able to stabilize the production of PDO (Protected Denomination of Origin) Pecorino Siciliano cheese, preserving its typicality. The experimental plan included the application of a multi-strain lactic acid bacteria (LAB) culture, composed of starter (Lactococcus lactis subsp. lactis CAG4 and CAG37) and non starter (Enterococcus faecalis PSL71, Lactococcus garviae PSL67 and Streptococcus macedonicus PSL72) strains, during the traditional production of cheese at large scale level in six factories located in different areas of Sicily. The cheese making processes were followed from milk to ripened cheeses and the effects of the added LAB were evaluated on the microbiological, chemico-physical and sensorial characteristics of the final products. Results highlighted a high variability for all investigated parameters and the dominance of LAB cocci in bulk milk samples. The experimental curds showed a faster pH drop than control curds and the levels of LAB estimated in 5 month ripened experimental cheeses (7.59 and 7.27 Log CFU/g for rods and cocci, respectively) were higher than those of control cheeses (7.02 and 6.61 Log CFU/g for rods and cocci, respectively). The comparison of the bacterial isolates by randomly amplified polymorphic DNA (RAPD)-PCR evidenced the dominance of the added starter lactococci over native milk and vat LAB, while the added non starter LAB were found at almost the same levels of the indigenous strains. The sensory evaluation showed that the mixed LAB culture did not influence the majority of the sensory attributes of the cheeses and that each factory produced cheeses with unique characteristics. Finally, the multivariate statistical analysis based on all parameters evaluated on the ripened cheeses showed the dissimilarities and the relationships among cheeses. Thus, the main hypothesis of the work was accepted since the quality parameters of the final cheeses were stabilized, but all cheeses maintained their local typicality. PMID- 27375246 TI - Detection and molecular characterization of norovirus from oysters implicated in outbreaks in the US. AB - Human noroviruses are the leading cause of non-bacterial shellfish associated gastroenteritis. Here we report on the detection and characterization of norovirus (NoV) in shellfish associated outbreaks. Requests were received from state and federal officials for technical assistance in the analysis of shellfish for NoV and male specific coliphage (MSC; an enteric virus surrogate) during the years 2009 thru 2014. In outbreaks where NoV was detected, genogroup II (GII) levels ranged from 2.4 to 82.0 RT-qPCR U/g of digestive diverticula (DD) while NoV genogroup I (GI) levels ranged from 1.5 to 29.8 RT-qPCR U/g of DD. Murine norovirus extraction efficiencies ranged between 50 and 85%. MSC levels ranged from <6 to 80 PFU/100 g. Phylogenetic analysis of the outbreak sequences revealed strains clustering with GI.8, GI.4, GII.3, GII.4, GII.7, and GII.21. There was 100% homology between the shellfish and clinical strains occurring in 2 of 8 outbreaks. Known shellfish consumption data demonstrated probable infectious particles ingested as low as 12. These investigations demonstrate effective detection, quantification, and characterization of NoV in shellfish associated with illness. PMID- 27375247 TI - Histamine-producing Lactobacillus parabuchneri strains isolated from grated cheese can form biofilms on stainless steel. AB - The consumption of food containing large amounts of histamine can lead to histamine poisoning. Cheese is one of the most frequently involved foods. Histamine, one of the biogenic amines (BAs) exhibiting the highest safety risk, accumulates in food contaminated by microorganisms with histidine decarboxylase activity. The origin of these microorganisms may be very diverse with contamination likely occurring during post-ripening processing, but the microorganisms involved during this manufacturing step have never been identified. The present work reports the isolation of 21 histamine-producing Lactobacillus parabuchneri strains from a histamine-containing grated cheese. PCR revealed that every isolate carried the histidine decarboxylase gene (hdcA). Eight lineages were identified based on the results of genome PFGE restriction analysis plus endonuclease restriction profile analysis of the carried plasmids. Members of all lineages were able to form biofilms on polystyrene and stainless steel surfaces. L. parabuchneri is therefore an undesirable species in the dairy industry; the biofilms it can produce on food processing equipment represent a reservoir of histamine-producing bacteria and thus a source of contamination of post-ripening-processed cheeses. PMID- 27375248 TI - Enterococci as indicator of potential growth of Salmonella in fresh minced meat at retail. AB - The present study had the purpose of demonstrating a positive correlation between enterococci and Salmonella in minced pork and beef. Data from 2001 to 2002 from retail minced pork and beef in Denmark were used and the association between concentration of enterococci and prevalence and concentration of Salmonella was examined. A total of 2187 and 2747 samples of minced pork and beef, respectively, were collected from butcher shops and supermarkets throughout the country. In pork, 2.1% of all samples were positive for Salmonella whereas 1.5% of beef samples were positive. Among samples with >=100 CFU/g of enterococci, prevalence of Salmonella positive samples was 3.4%, which was significantly higher than 1.2% observed in minced meat with less than 100 CFU/g of enterococci (P < 0.001). A positive association between occurrence of enterococci and presence of Salmonella in retail minced meat was supported as both prevalence and concentration of Salmonella in positive samples increased with increasing concentrations of enterococci in minced meat. From our data, we suggest that minced meat containing more than 500 enterococci per gram is suspected of having been exposed to temperatures allowing growth of Salmonella. This is to our knowledge the first report, which links presence of an indicator to potential growth of Salmonella. PMID- 27375249 TI - Prevalence and behavior of multidrug-resistant shiga toxin-producing Escherichia coli, enteropathogenic E. coli and enterotoxigenic E. coli on coriander. AB - The prevalence and behavior of multidrug-resistant diarrheagenic Escherichia coli pathotypes on coriander was determined. One hundred coriander samples were collected from markets. Generic E. coli were determined using the most probable number procedure. Diarrheagenic E. coli pathotypes (DEPs) were identified using two multiplex polymerase chain reaction procedures. Susceptibility to sixteen antibiotics was tested for the isolated DEPs strains by standard test. The behavior of multidrug-resistant DEPs isolated from coriander was determined on coriander leaves and chopped coriander at 25 degrees +/- 2 degrees C and 3 degrees +/- 2 degrees C. Generic E. coli and DEPs were identified, respectively, in 43 and 7% of samples. Nine DEPs strains were isolated from positive coriander samples. The identified DEPs included Shiga toxin-producing E. coli (STEC, 4%) enterotoxigenic E. coli (ETEC, 2%) and enteropathogenic E. coli (EPEC, 1%). All isolated DEPs strains exhibited multi-resistance to antibiotics. On inoculated coriander leaves stored at 25 degrees +/- 2 degrees C or 3 degrees +/- 2 degrees C, no growth was observed for multidrug-resistant DEPs strains. However, multidrug-resistant DEPs strains grew in chopped coriander: after 24 h at 25 degrees +/- 2 degrees C, DEPs strains had grown to approximately 3 log CFU/g. However, at 3 degrees +/- 2 degrees C the bacterial growth was inhibited. To the best of our knowledge, this is the first report of the presence and behavior of multidrug-resistant STEC, ETEC and EPEC on coriander and chopped coriander. PMID- 27375250 TI - Survival of foodborne pathogens in natural cracked olive brines. AB - This work reports the survival (challenge tests) of foodborne pathogen species (Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, and Salmonella enterica) in Alorena de Malaga table olive brines. The inhibitions were fit using a log-linear model with tail implemented in GInaFIT excel software. The olive brine had a considerable inhibitory effect on the pathogens. The residual (final) populations (Fp) after 24 h was below detection limit (<1.30 log10 cfu/mL) for all species assayed. The maximum death rate (kmax) was 9.98, 51.37, 38.35 and 53.01 h(-1), while the time for 4 log10 reductions (4Dr) was 0.96, 0.36, 0.36 and 0.24 h for E. coli, S. aureus, L. monocytogenes and S. enterica, respectively. Brine dilutions increased Fp and 4Dr, while decreased kmax. A cluster analysis showed that E. coli had an overall quite different behaviour being the most resistant species, but the others bacteria behaved similarly, especially S. aureus and S. enterica. Partial Least Squares regression showed that the most influential phenols on microbial survival were EDA (dialdehydic form of decarboxymethyl elenolic acid), HyEDA (EDA linked to hydroxytyrosol), hydroxytyrosol 4-glucoside, tyrosol, and oleoside 11-methyl ester. Results confirm the adverse habitats of table olives for foodborne pathogenic microorganisms. PMID- 27375251 TI - Fate of Lactococcus lactis starter cultures during late ripening in cheese models. AB - The presence of Lactococcus lactis, commonly employed as starter culture, was, recently, highlighted and investigated during late cheese ripening. Thus, the main goal of the present study was to assess the persistence and viability of this microorganism throughout manufacturing and ripening of model cheeses. Eight commercial starters, constituted of L. lactis subsp. lactis and L. lactis subsp. cremoris, were inoculated in pasteurized milk in order to manufacture miniature cheeses, ripened for six months. Samples were analysed at different steps (milk after inoculum, curd after cutting, curd after pressing and draining, cheese immediately after salting and cheese at 7, 15, 30, 60, 90, 120, 150 and 180 days of ripening) and submitted to both culture-dependent (traditional plating on M17) and -independent analysis (reverse transcription-quantitative PCR). On the basis of direct RNA analysis, L. lactis populations were detected in all miniature cheeses up to the sixth month of ripening, confirming the presence of viable cells during the whole ripening process, including late stages. Noteworthy, L. lactis was detected by RT-qPCR in cheese samples also when traditional plating failed to indicate its presence. This discrepancy could be explain with the fact that lactococci, during ripening process, enter in a stressed physiological state (viable not culturable, VNC), which might cause their inability to grow on synthetic medium despite their viability in cheese matrix. Preliminary results obtained by "resuscitation" assays corroborated this hypothesis and 2.5% glucose enrichment was effective to recover L. lactis cells in VNC state. The capability of L. lactis to persist in late ripening, and the presence of VNC cells which are known to shift their catabolism to peptides and amino acids consumption, suggests a possible technological role of this microorganism in cheese ripening with a possible impact on flavour formation. PMID- 27375252 TI - Combined effect of anaerobiosis, low pH and cold temperatures on the growth capacities of psychrotrophic Bacillus cereus. AB - Psychrotrophic strains of the foodborne pathogen Bacillus cereus can multiply during the refrigerated storage of food products. The aim of this study was to determine the impact of anaerobiosis on the growth of two psychrotrophic B. cereus strains exposed to acidic pH at a cold temperature in a laboratory medium. At 10 degrees C, growth occurred at pH values equal to or higher than 5.7 during anaerobiosis, whereas aerobic growth was observed from pH 5.4. Growth rates during aerobiosis were similar at pH 5.4 and pH 7. No growth was observed for the two tested strains at 8 degrees C without oxygen regardless of the pH; however, both strains grew at this temperature from pH 5.4 in the presence of oxygen. These pH growth limits in aerobiosis are consistent with those reported for different strains and different foods or media, but no other studies have described anaerobic growth at acidic pH values. The maximal B. cereus concentration was approximately 6.0 log10 CFU/ml for cultures in the absence of oxygen and approximately 8.0 log10 CFU/ml for cultures in the presence of oxygen. In conclusion, we found that the combination of anaerobiosis, pH < 5.7 at 10 degrees C, or anaerobiosis and temperatures <=8 degrees C prevent psychrotrophic B. cereus growth. PMID- 27375253 TI - Natural plant products inhibits growth and alters the swarming motility, biofilm formation, and expression of virulence genes in enteroaggregative and enterohemorrhagic Escherichia coli. AB - The purpose of this study was to determine the effects of plant products on the growth, swarming motility, biofilm formation and virulence gene expression in enterohemorrhagic Escherichia coli O157:H7 and enteroaggregative E. coli strain 042 and a strain of O104:H4 serotype. Extracts of Lippia graveolens and Haematoxylon brassiletto, and carvacrol, brazilin were tested by an antimicrobial microdilution method using citral and rifaximin as controls. All products showed bactericidal activity with minimal bactericidal concentrations ranging from 0.08 to 8.1 mg/ml. Swarming motility was determined in soft LB agar. Most compounds reduced swarming motility by 7%-100%; except carvacrol which promoted motility in two strains. Biofilm formation studies were done in microtiter plates. Rifaximin inhibited growth and reduced biofilm formation, but various concentrations of other compounds actually induced biofilm formation. Real time PCR showed that most compounds decreased stx2 expression. The expression of pic and rpoS in E. coli 042 were suppressed but in E. coli O104:H4 they varied depending on compounds. In conclusion, these extracts affect E. coli growth, swarming motility and virulence gene expression. Although these compounds were bactericidal for pathogenic E. coli, sublethal concentrations had varied effects on phenotypic and genotypic traits, and some increased virulence gene expression. PMID- 27375254 TI - Antilisterial peptides from Spanish dry-cured hams: Purification and identification. AB - The typical Spanish dry-cured ham has a particular sensory quality that makes it a distinctive food, highly appreciated for consumers worldwide. Its particular physicochemical properties, such as high salt content and reduced water activity contribute to their shelf-stability. However, post-processing actions carried out for the commercialization of these products such as slicing may increase the risk of development of pathogenic microorganisms as Listeria monocytogenes. During ripening, muscle proteins are hydrolyzed by muscle peptidases releasing peptides and free amino acids. Some of these peptides have been described to exert biological activities such as antioxidant and ACE-inhibition. In this study, a peptidomic strategy using mass spectrometry techniques has been used to identify and sequence those naturally generated peptides showing antilisterial activity. One hundred and five peptides have been identified in active fractions and some synthesized and their MIC calculated. Ten peptides were able to inhibit the growth of L. monocytogenes, being the pentapeptide RHGYM the most effective showing a MIC value of 6.25 mM. This study proves for the first time the potential antimicrobial action against L. monocytogenes of certain naturally generated peptides obtained from Spanish dry-cured ham. PMID- 27375255 TI - Polyphenolic extracts of cherry (Prunus cerasus L.) and blackcurrant (Ribes nigrum L.) leaves as natural preservatives in meat products. AB - The objective of this study was to evaluate the possibility of using polyphenolic extracts from cherry and blackcurrant leaves as natural antimicrobial agents in meat products. The polyphenolic composition of the extracts was analyzed and their impact on the microbial quality, lipid oxidation, color, and sensory evaluation of pork sausages was studied. Polyphenolic extracts were obtained from leaves collected in September. The total polyphenolic content in sour cherry leaf extract was 1.5 times higher than that found in blackcurrant leaf extract. Analysis of the polyphenol profile of each extract revealed two major groups: phenolic acids and flavonoids, including epigallocatechin and glycosides of quercetin and kaempferol. After chilling the sausages for 14 and 28 days, the extracts caused significantly lower MDA generation, indicating an antioxidant effect. Color changes after 28 days of storage were perceptible in the case of all treatments, with and without polyphenols. The application of sour cherry and black currant leaf extracts increased the shelf life of vacuum-packed sausages. Both extracts enhanced the microbial quality of the pork sausages over 14 days of refrigerated storage. Sour cherry leaf polyphenols were more effective against almost all studied groups of microorganisms. PMID- 27375256 TI - Using mixed inocula of Saccharomyces cerevisiae killer strains to improve the quality of traditional sparkling-wine. AB - The quality of traditional sparkling-wine depends on the aging process in the presence of dead yeast cells. These cells undergo a slow autolysis process thereby releasing some compounds, mostly colloidal polymers such as polysaccharides and mannoproteins, which influence the wine's foam properties and mouthfeel. Saccharomyces cerevisiae killer yeasts were tested to increase cell death and autolysis during mixed-yeast-inoculated second fermentation and aging. These yeasts killed sensitive strains in killer plate assays done under conditions of low pH and temperature similar to those used in sparkling-wine making, although some strains showed a different killer behaviour during the second fermentation. The fast killer effect improved the foam quality and mouthfeel of the mixed-inoculated wines, while the slow killer effect gave small improvements over single-inoculated wines. The effect was faster under high pressure than under low-pressure conditions. Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. PMID- 27375257 TI - Brettanomyces bruxellensis, a survivalist prepared for the wine apocalypse and other beverages. AB - Brettanomyces bruxellensis is a common red wine spoilage yeast. Yet, in addition to wine, it has been isolated from other ecological niches that are just as nutritionally deficient as wine. B. bruxellensis can therefore be regarded as a survivor, well adapted to colonise harsh environments not often inhabited by other yeasts. This review is focused on the nutritional requirements of B. bruxellensis and the relevance thereof for its adaptation to the different matrices within which it occurs. Furthermore, the environmental conditions necessary (e.g. aerobic or anaerobic conditions) for the assimilation of the carbon or nitrogenous sources are discussed in this review. From literature, several confusing inconsistencies, regarding nutritional sources necessary for B. bruxellensis survival, in these specialist ecological niches are evidenced. The main focus of this review is wine but other products and niches that B. bruxellensis inhabits namely beer, cider, fruit juices and bioethanol production plants are also considered. This review highlights the lack of knowledge regarding B. bruxellensis when considering its nutritional requirements in comparison to Saccharomyces cerevisiae. However, there is a large enough body of evidence showing that the nutritional needs of B. bruxellensis are meagre, explaining its ability to colonise harsh environments. PMID- 27375258 TI - Exploitation of Leuconostoc mesenteroides strains to improve shelf life, rheological, sensory and functional features of prickly pear (Opuntia ficus indica L.) fruit puree. AB - Strains of Leuconostoc mesenteroides were identified from raw prickly pear (Opuntia ficus-indica L.). Five autochthonous strains were selected based on the kinetics of growth and acidification on prickly pear fruit juice, and the capacity to synthesize exo-polysaccharides. All selected Leuc. mesenteroides strains showed an in vitro mucilage-degrading capability. A protocol for processing and storage of fermented prickly pear fruit puree (FP) was set up. Unstarted FP and chemically acidified FP were used as the controls. Starters grew and remained viable at elevated cell numbers during 21 days of storage at 4 degrees C. Contaminating Enterobacteriaceae and yeasts were found only in the controls. Viscosity and serum separation distinguished started FP compared to the controls. Colour parameters, browning index, sensory attributes, antimicrobial activity, vitamin C and betalains levels were positively affected by lactic acid fermentation. Increase of free radical scavenging activity in ethyl acetate soluble extract suggested an effect of selected strains on phenolic profiles. Started FP markedly inhibited the inflammatory status of Caco-2/TC7 cells, and also contributed to maintaining the integrity of tight junctions. Started FP scavenged the reactive oxygen species generated by H2O2 on Caco-2 cells. All selected strain variously affected the immunomodulatory activity towards anti- and pro-inflammatory cytokines. PMID- 27375259 TI - Long-term survival of the Shiga toxin-producing Escherichia coli O104:H4 outbreak strain on fenugreek seeds. AB - A major outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 occurred in Germany in 2011. The epidemiological investigation revealed that a contaminated batch of fenugreek seeds (Trigonella foenum-graecum) was the most probable source of the pathogen. It was suggested that the most probable point of contamination was prior to leaving the importer, meaning that the seed contamination with STEC O104:H4 should have happened more than one year before the seeds were used for sprout production. Here, we investigated the capacity of STEC O104:H4 and closely related pathogenic as well as non-pathogenic Escherichia coli strains for long-term survival on dry fenugreek seeds. We did not observe a superior survival capacity of STEC O104:H4 on dry seeds. For none of the strains tested cultivatable cells were found without enrichment on contaminated seeds after more than 24 weeks of storage. Our findings suggest that contamination previous to the distribution from the importer may be less likely than previously assumed. We show that seeds contaminated with E. coli in extremely high numbers can be completely sterilized by a short treatment with bleach. This simple and cheap procedure does not affect the germination capacity of the seeds and could significantly improve safety in sprout production. PMID- 27375260 TI - Viable But Not Culturable (VBNC) state of Brettanomyces bruxellensis in wine: New insights on molecular basis of VBNC behaviour using a transcriptomic approach. AB - The spoilage potential of Brettanomyces bruxellensis in wine is strongly connected with the aptitude of this yeast to enter in a Viable But Non Culturable (VBNC) state when exposed to the harsh wine conditions. In this work, we characterized the VBNC behaviour of seven strains of B. bruxellensis representing a regional intraspecific biodiversity, reporting conclusive evidence for the assessment of VBNC as a strain-dependent character. The VBNC behaviour was monitored by fluorescein diacetate staining/flow cytometry for eleven days after addition of 0.4, 0.6, 0.8, 1 and 1.2 mg/L of molecular SO2 (entrance in the VBNC state) and after SO2 removal (exit from the VBNC state). Furthermore, one representative strain was selected and RNA-seq analysis performed after exposure to 1.2 mg/L SO2 and during the recovery phase. 30 and 1634 genes were identified as differentially expressed following VBNC entrance and 'resuscitation', respectively. The results reported strongly suggested that the entrance in the SO2-induced VBNC state in B. bruxellensis is associated with both, sulfite toxicity and oxidative stress response, confirming the crucial role of genes/proteins involved in redox cell homeostasis. Among the genes induced during recovery, the expression of genes involved in carbohydrate metabolism and encoding heat shock proteins, as well as enriched categories including amino acid transport and transporter activity was observed. The evidences of a general repression of genes involved in DNA replication suggest the occurrence of a true resuscitation of cell rather than a simple regrowth. PMID- 27375261 TI - Characterization of the spore surface and exosporium proteins of Clostridium sporogenes; implications for Clostridium botulinum group I strains. AB - Clostridium sporogenes is a non-pathogenic close relative and surrogate for Group I (proteolytic) neurotoxin-producing Clostridium botulinum strains. The exosporium, the sac-like outermost layer of spores of these species, is likely to contribute to adhesion, dissemination, and virulence. A paracrystalline array, hairy nap, and several appendages were detected in the exosporium of C. sporogenes strain NCIMB 701792 by EM and AFM. The protein composition of purified exosporium was explored by LC-MS/MS of tryptic peptides from major individual SDS PAGE-separated protein bands, and from bulk exosporium. Two high molecular weight protein bands both contained the same protein with a collagen-like repeat domain, the probable constituent of the hairy nap, as well as cysteine-rich proteins CsxA and CsxB. A third cysteine-rich protein (CsxC) was also identified. These three proteins are also encoded in C. botulinum Prevot 594, and homologues (75-100% amino acid identity) are encoded in many other Group I strains. This work provides the first insight into the likely composition and organization of the exosporium of Group I C. botulinum spores. PMID- 27375262 TI - Genomic approach to studying nutritional requirements of Clostridium tyrobutyricum and other Clostridia causing late blowing defects. AB - Clostridium tyrobutyricum is the main microorganism responsible for the late blowing defect in hard and semi-hard cheeses, causing considerable economic losses to the cheese industry. Deeper knowledge of the metabolic requirements of this microorganism can lead to the development of more effective control approaches. In this work, the amino acids and B vitamins essential for sustaining the growth of C. tyrobutyricum were investigated using a genomic approach. As the first step, the genomes of four C. tyrobutyricum strains were analyzed for the presence of genes putatively involved in the biosynthesis of amino acids and B vitamins. Metabolic pathways could be reconstructed for all amino acids and B vitamins with the exception of biotin (vitamin B7) and folate (vitamin B9). The biotin pathway was missing the enzyme amino-7-oxononanoate synthase that catalyzes the condensation of pimeloyl-ACP and l-alanine to 8-amino-7 oxononanoate. In the folate pathway, the missing genes were those coding for para aminobenzoate synthase and aminodeoxychorismate lyase enzymes. These enzymes are responsible for the conversion of chorismate into para-aminobenzoate (PABA). Two C. tyrobutyircum strains whose genome was analyzed in silico as well as other 10 strains isolated from cheese were tested in liquid media to confirm these observations. 11 strains showed growth in a defined liquid medium containing biotin and PABA after 6-8 days of incubation. No strain showed growth when only one or none of these compounds were added, confirming the observations obtained in silico. Furthermore, the genome analysis was extended to genomes of single strains of other Clostridium species potentially causing late blowing, namely Clostridium beijerinckii, Clostridium sporogenes and Clostridium butyricum. Only the biotin biosynthesis pathway was incomplete for C. butyricum and C. beijerincki. In contrast, C. sporogenes showed missing enzymes in biosynthesis pathways of several amino acids as well as biotin, folate, and cobalamin (vitamin B12). These observations agree with the results of growth experiments of these species in liquid media reported in the literature. The results of this study suggest that biotin and folate are potential targets for reducing late blowing in cheese and highlight the usefulness of genomic analysis for identifying essential nutrients in bacteria. PMID- 27375264 TI - The butterfly - a well-defined constant-current topography pattern on Si(001):H and Ge(001):H resulting from current-induced defect fluctuations. AB - Dangling bond (DB) arrays on Si(001):H and Ge(001):H surfaces can be patterned with atomic precision and they exhibit complex and rich physics making them interesting from both technological and fundamental perspectives. But their complex behavior often makes scanning tunneling microscopy (STM) images difficult to interpret and simulate. Recently it was shown that low-temperature imaging of unoccupied states of an unpassivated dimer on Ge(001):H results in a symmetric butterfly-like STM pattern, despite the fact that the equilibrium dimer configuration is expected to be a bistable, buckled geometry. Here, based on a thorough characterization of the low-bias switching events on Ge(001):H, we propose a new imaging model featuring a dynamical two-state rate equation. On both Si(001):H and Ge(001):H, this model allows us to reproduce the features of the observed symmetric empty-state images which strongly corroborates the idea that the patterns arise due to fast switching events and provides an insight into the relationship between the tunneling current and switching rates. We envision that our new imaging model can be applied to simulate other bistable systems where fluctuations arise from transiently charged electronic states. PMID- 27375263 TI - Intestinal gas and liver steatosis: a casual association? A prospective multicentre assessment. AB - BACKGROUND & AIMS: Excessive intestinal gas and liver steatosis are frequent sonographic findings. Both of these appear to be caused by variations of the gut microflora. We assessed the relationship between ultrasonographic detection of intestinal gas and liver steatosis. METHODS: This study included 204 consecutive patients (99 male; mean age 53.0 +/- 15.6 years), who underwent ultrasonography for abdominal complaints or follow-up of benign lesions. Body mass index, biochemical liver markers, sonographic presence of liver steatosis and/or degree of intestinal gas interfering with the examination were collected. Both sonographic findings were assessed based on standardized criteria. The association between liver steatosis and intestinal gas was evaluated by means of univariate and multivariate analyses. RESULTS: Eighty (39.2%) of patients showed moderate to large amounts of gas preventing an accurate evaluation of the liver or pancreas and 90 (44.1%) had liver steatosis. A significant correlation between the degree of intestinal gas and liver steatosis both in obese (r=.603; P<.001) and in nonobese patients (r=.555; P<.001) was found. Univariate analysis showed that intestinal gas, body mass index, aspartate transaminase, alanine transaminase, gamma-GT, age and sex were predictors of liver steatosis; only intestinal gas (OR 7.4; 95% CI 3.4-16.1) and body mass index (OR; 1.4, 95% CI 1.2 1.5), however, were independent predictors at multivariate analysis. The presence of excessive gas was also significantly correlated with liver steatosis coupled with elevated ALT (P = .001). CONCLUSION: This study shows a significant correlation between excessive intestinal gas and liver steatosis. The reasons of this finding and its clinical implications remain to be defined. PMID- 27375265 TI - An assessment of the existence and influence of psychoanalytic jurisprudence in the United States. AB - In light of the ongoing controversy over the value of psychoanalysis generally, this article summarizes the standards for scientific expertise in law and concludes that the future of psychoanalytic jurisprudence does not lie in the courtroom. After a brief survey of the history of psychoanalytic jurisprudence in legal contexts and institutions, I identify a revival of psychoanalytic jurisprudence, including (i) its association, primarily as a social theory, with Critical Legal Studies (in the US context), and (ii) the influence of Jacques Lacan in the legal academy. The unifying themes in this critical methodology include the construction of the subject through the language and rituals of the law, the failure of mainstream jurisprudence to be sufficiently critical of the legal status quo, and the repression or denial of injustices in legal history. Paralleling that revival, I note that a field of scholarship employing traditional Freudian conceptions is also currently engaging interdisciplinary legal studies, intervening in law reform efforts (particularly in criminal law), and criticizing the background assumptions and conventions in contemporary judicial opinions. I conclude that psychoanalysis is both threatening to mainstream legal culture and a rich source of insights for contemporary studies of legal processes and institutions. PMID- 27375266 TI - An Update on Fetal Alcohol Syndrome-Pathogenesis, Risks, and Treatment. AB - Alcohol is a well-established teratogen that can cause variable physical and behavioral effects on the fetus. The most severe condition in this spectrum of diseases is known as fetal alcohol syndrome (FAS). The differences in maternal and fetal enzymes, in terms of abundance and efficiency, in addition to reduced elimination, allow for alcohol to have a prolonged effect on the fetus. This can act as a teratogen through numerous methods including reactive oxygen species (generated as by products of CYP2E1), decreased endogenous antioxidant levels, mitochondrial damage, lipid peroxidation, disrupted neuronal cell-cell adhesion, placental vasoconstriction, and inhibition of cofactors required for fetal growth and development. More recently, alcohol has also been shown to have epigenetic effects. Increased fetal exposure to alcohol and sustained alcohol intake during any trimester of pregnancy is associated with an increased risk of FAS. Other risk factors include genetic influences, maternal characteristics, for example, lower socioeconomic statuses and smoking, and paternal chronic alcohol use. The treatment options for FAS have recently started to be explored although none are currently approved clinically. These include prenatal antioxidant administration food supplements, folic acid, choline, neuroactive peptides, and neurotrophic growth factors. Tackling the wider impacts of FAS, such as comorbidities, and the family system have been shown to improve the quality of life of FAS patients. This review aimed to focus on the pathogenesis, especially mechanisms of alcohol teratogenicity, and risks of developing FAS. Recent developments in potential management strategies, including prenatal interventions, are discussed. PMID- 27375267 TI - An accurate cost effective DFT approach to study the sensing behaviour of polypyrrole towards nitrate ions in gas and aqueous phases. AB - Density functional theory (DFT) calculations have been performed to study the response of polypyrrole towards nitrate ions in gas and aqueous phases. First, an accurate estimate of interaction energies is obtained by methods calibrated against the gold standard CCSD(T) method. Then, a number of low cost DFT methods are also evaluated for their ability to accurately estimate the binding energies of polymer-nitrate complexes. The low cost methods evaluated here include dispersion corrected potential (DCP), Grimme's D3 correction, counterpoise correction of the B3LYP method, and Minnesota functionals (M05-2X). The interaction energies calculated using the counterpoise (CP) correction and DCP methods at the B3LYP level are in better agreement with the interaction energies calculated using the calibrated methods. The interaction energies of an infinite polymer (polypyrrole) with nitrate ions are calculated by a variety of low cost methods in order to find the associated errors. The electronic and spectroscopic properties of polypyrrole oligomers nPy (where n = 1-9) and nPy-NO3(-) complexes are calculated, and then extrapolated for an infinite polymer through a second degree polynomial fit. Charge analysis, frontier molecular orbital (FMO) analysis and density of state studies also reveal the sensing ability of polypyrrole towards nitrate ions. Interaction energies, charge analysis and density of states analyses illustrate that the response of polypyrrole towards nitrate ions is considerably reduced in the aqueous medium (compared to the gas phase). PMID- 27375268 TI - In vitro maturation of immature rat oocytes under simple culture conditions and subsequent developmental ability. AB - Rat oocytes can be produced artificially by superovulation. Because some strains show low sensitivity to superovulation treatment, in vitro maturation is an alternative method to produce numerous matured oocytes. Furthermore, establishment of an in vitro maturation system with simple culture conditions is cost effective and leads to easy handling of oocytes. This study examined developmental ability of rat germinal vesicle (GV) oocytes maturing in vitro under simple culture conditions. Significantly different numbers of ovulated oocytes reached the second metaphase of meiosis (MII) among Jcl:Wistar (17.0), F344/Stm (31.0), and BN/SsNSlc (2.2) rats in whom superovulation was induced by pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin. However, similar numbers of GV oocytes were obtained from ovaries of PMSG injected Wistar (27.7), F344 (34.7), and BN (24.7) rats. These GV oocytes were cultured in vitro in HTF, alphaMEM, and a 1:1 HTF + alphaMEM or TYH + alphaMEM mixture. High proportions of Wistar and F344 oocytes that matured to MII in alphaMEM were parthenogenetically activated by strontium chloride treatment (78% and 74%, respectively). Additionally, 10% of matured oocytes of both strains developed into offspring after intracytoplasmic sperm injection and embryo transfer to foster mothers. Although BN oocytes cultured in alphaMEM could be parthenogenetically activated and developed into offspring, the success rate was lower than that for Wistar and F344 oocytes. This study demonstrated that numerous GV oocytes were produced in rat ovaries by PMSG injection. This simple in vitro maturation system of immature oocytes could be further developed to maintain valuable rat strains experiencing reproductive difficulties. PMID- 27375269 TI - Distribution of rotavirus VP7 and VP4 genotypes circulating in Tunisia from 2009 to 2014: Emergence of the genotype G12. AB - Group A rotavirus (RVA) represents the most important aetiological agent of diarrhoea in children worldwide. From January 2009 to December 2014, a multi centre study realized through 11 Tunisian cities was undertaken among children aged <5 years consulting or hospitalized for acute gastroenteritis. A total of 1127 faecal samples were collected. All samples were screened by ELISA for the presence of RVA antigen. RVA-positive samples were further analyzed by PAGE and used for G/P-genotyping by semi-nested multiplex RT-PCR. Globally, 270 specimens (24 %) were RVA-positive, with peaks observed annually between November and March. Nine different electropherotypes could be visualized by PAGE, six with a long profile (173 cases) and two with a short one (seven cases). Mixed profiles were detected in two cases. Among the 267 VP7 genotyped strains, the predominant G- genotype was G1 (39.6 %) followed by G3 (22.2 %), G4 (13 %), G9 (11.5 %), G2 (5.2 %) and G12 (5.2 %). Among the 260 VP4 genotyped strains, P[8] genotype was the predominant (74.5 %) followed by P[6] (10.4 %) and P[4] (5.5 %). A total of 257 strains (95.2 %) could be successfully G- and P-genotyped. G1P[8] was the most prevalent combination (34.4 %), followed by G3P[8] (16.3 %), G9P[8] (10.3 %), G4P[8] (8.9 %), G2P[4] (4 %), G12P[6] (2.6 %) and G12P[8] (1.9 %). Uncommon G/Pgenotype combinations, mixed infections and untypeable strains were also detected. This is the first report, in Tunisia, of multiple detection of an emerging human RVA strain, G12 genotype. This study highlighted the need for maintaining active surveillance of emerging strains in Northern Africa. PMID- 27375270 TI - Robust Anti-Icing Performance of a Flexible Superhydrophobic Surface. AB - A material with superhydrophobic and anti-ice/de-icing properties, which has a micro-/nanostructured surface, is produced by a straightforward method. This material comprises a poly(dimethylsiloxane) (PDMS) microstructure with ZnO nanohairs and shows excellent water and ice repellency even at low temperatures ( 20 degrees C) and relatively high humidity (90%) for over three months. These results are expected to be helpful for designing smart, non-wetting materials that can be adapted to low-temperature environments for the development of anti icing systems. PMID- 27375271 TI - Construction and Characterization of Two Novel Transcriptome Assemblies in the Congeneric Porcelain Crabs Petrolisthes cinctipes and P. manimaculis. AB - Crustaceans have commonly been used as non-model systems in basic biological research, especially physiological regulation. With the recent and rapid adoption of functional genomic tools, crustaceans are increasingly becoming model systems for ecological investigations of development and evolution and for mechanistic examinations of genotype-phenotype interactions and molecular pathways of response to environmental stressors. Comparative transcriptomic approaches, however, remain constrained by a lack of sequence data in closely related crustacean taxa. We identify challenges in the use of functional genomics tools in comparative analysis among decapod crustacean in light of recent advances. We present RNA-seq data from two congeneric species of porcelain crabs (Petrolisthes cinctipes and P. manimaculis) used to construct two de novo transcriptome assemblies with ~194K and ~278K contigs, respectively. We characterize and contrast these assemblies and compare them to a previously generated EST sequence library for P. cinctipes We also discuss the potential use of these data as a case-study system in the broader context of crustacean comparative transcriptomics. PMID- 27375272 TI - Evolution of Venomous Cartilaginous and Ray-Finned Fishes. AB - Venom and its associated delivery systems have evolved in numerous animal groups ranging from jellyfishes to spiders, lizards, shrews, and the male platypus. Building off new data and previously published anatomical and molecular studies, we explore the evolution of and variation within venomous fishes. We show the results of the first multi-locus, ordinal-level phylogenetic analysis of cartilaginous (Chondrichthyes) and ray-finned (Actinopterygii) fishes that hypothesizes 18 independent evolutions of this specialization. Ancestral-states reconstruction indicates that among the 2386-2962 extant venomous fishes, envenomed structures have evolved four times in cartilaginous fishes, once in eels (Anguilliformes), once in catfishes (Siluriformes), and 12 times in spiny rayed fishes (Acanthomorpha). From our anatomical studies and phylogenetic reconstruction, we show that dorsal spines are the most common envenomed structures (~95% of venomous fish species and 15 independent evolutions). In addition to envenomed spines, fishes have also evolved venomous fangs (2% of venomous fish species, two independent evolutions), cleithral spines (2% of venomous fish species, one independent evolution), and opercular or subopercular spines (1% of venomous fish species, three independent evolutions). PMID- 27375273 TI - Introduction to the Symposium: Parasites and Pests in Motion: Biology, Biodiversity and Climate Change. AB - Although climate change can cause extreme alterations to ecosystems, only limited research has investigated how altered physical conditions (e.g., warming, extreme temperature events, sea level rise, ocean acidification, and altered precipitation) influence species interactions. In particular, the interplay between host and parasites in such a changing world is in need of study. Our objective in organizing this symposium was to bring together researchers working on a wide variety of natural enemies (parasites, pathogens, and pests), to exchange knowledge on how aspects of global climate change may alter the distribution and ecology of these organisms and their hosts. It is our intention that the symposium and the resulting articles will foster more accurate modeling of and predictions about the impacts of climate change on the biology and ecology of natural enemies and their hosts. PMID- 27375274 TI - The Impact of Organismal Innovation on Functional and Ecological Diversification. AB - Innovations in organismal functional morphology are thought to be a major force in shaping evolutionary patterns, with the potential to drive adaptive radiation and influence the evolutionary prospects for lineages. But the evolutionary consequences of innovation are diverse and usually do not result in adaptive radiation. What factors shape the macroevolutionary impact of innovations? We assert that little is known in general about the macroevolutionary outcomes associated with functional innovations and we discuss a framework for studying biological innovations in an evolutionary context. Innovations are novel functional mechanisms that enhance organismal performance. The ubiquity of trade offs in functional systems means that enhanced performance on one axis often occurs at the expense of performance on another axis, such that many innovations result in an exchange of performance capabilities, rather than an expansion. Innovations may open up new resources for exploitation but their consequences for functional and ecological diversification depend heavily on the adaptive landscape around these novel resources. As an example of a broader program that we imagine, we survey five feeding innovations in labrid fishes, an exceptionally successful and ecologically diverse group of reef fishes, and explore their impact on the rate of evolution of jaw functional morphology. All of the innovations provide performance enhancements and result in changes in patterns of resource use, but most are not associated with subsequent functional diversification or substantial ecological diversification. Because selection acts on a specific performance enhancement and not on the evolutionary potential of an innovation, the enhancement of diversity may be highly serendipitous. The macroevolutionary potential of innovations depends critically on the interaction between the performance enhancement and the ecological opportunity that is exposed. PMID- 27375275 TI - Combined treatment with cotylenin A and phenethyl isothiocyanate induces strong antitumor activity mainly through the induction of ferroptotic cell death in human pancreatic cancer cells. AB - The treatment of pancreatic cancer, one of the most aggressive gastrointestinal tract malignancies, with current chemotherapeutic drugs has had limited success due to its chemoresistance and poor prognosis. Therefore, the development of new drugs or effective combination therapies is urgently needed. Cotylenin A (CN-A) (a plant growth regulator) is a potent inducer of differentiation in myeloid leukemia cells and exhibits potent antitumor activities in several cancer cell lines. In the present study, we demonstrated that CN-A and phenethyl isothiocyanate (PEITC), an inducer of reactive oxygen species (ROS) and a dietary anticarcinogenic compound, synergistically inhibited the proliferation of MIAPaCa 2, PANC-1 and gemcitabine-resistant PANC-1 cells. A combined treatment with CN-A and PEITC also effectively inhibited the anchorage-independent growth of these cancer cells. The combined treatment with CN-A and PEITC strongly induced cell death within 1 day at concentrations at which CN-A or PEITC alone did not affect cell viability. A combined treatment with synthetic CN-A derivatives (ISIR-005 and ISIR-042) or fusicoccin J (CN-A-related natural product) and PEITC did not have synergistic effects on cell death. The combined treatment with CN-A and PEITC synergistically induced the generation of ROS. Antioxidants (N acetylcysteine and trolox), ferroptosis inhibitors (ferrostatin-1 and liproxstatin), and the lysosomal iron chelator deferoxamine canceled the synergistic cell death. Apoptosis inhibitors (Z-VAD-FMK and Q-VD-OPH) and the necrosis inhibitor necrostatin-1s did not inhibit synergistic cell death. Autophagy inhibitors (3-metyladenine and chloroquine) partially prevented cell death. These results show that synergistic cell death induced by the combined treatment with CN-A and PEITC is mainly due to the induction of ferroptosis. Therefore, the combination of CN-A and PEITC has potential as a novel therapeutic strategy against pancreatic cancer. PMID- 27375278 TI - A general iodine-mediated synthesis of primary sulfonamides from thiols and aqueous ammonia. AB - A general and efficient methodology for preparing primary sulfonamides has been developed. In the presence of iodine as the catalyst and TBHP (70% in water) as the oxidant, a wide range of primary sulfonamides were prepared from the corresponding thiols and aqueous ammonia in moderate to good yields. PMID- 27375277 TI - Human behavioral assessments in current research of Parkinson's disease. AB - Parkinson's disease (PD) is traditionally classified as a movement disorder because patients mainly complain about motor symptoms. Recently, non-motor symptoms of PD have been recognized by clinicians and scientists as early signs of PD, and they are detrimental factors in the quality of life in advanced PD patients. It is crucial to comprehensively understand the essence of behavioral assessments, from the simplest measurement of certain symptoms to complex neuropsychological tasks. We have recently reviewed behavioral assessments in PD research with animal models (Asakawa et al., 2016). As a companion volume, this article will systematically review the behavioral assessments of motor and non motor PD symptoms of human patients in current research. The major aims of this article are: (1) promoting a comparative understanding of various behavioral assessments in terms of the principle and measuring indexes; (2) addressing the major strengths and weaknesses of these behavioral assessments for a better selection of tasks/tests in order to avoid biased conclusions due to inappropriate assessments; and (3) presenting new concepts regarding the development of wearable devices and mobile internet in future assessments. In conclusion we emphasize the importance of improving the assessments for non-motor symptoms because of their complex and unique mechanisms in human PD brains. PMID- 27375276 TI - Active inference and learning. AB - This paper offers an active inference account of choice behaviour and learning. It focuses on the distinction between goal-directed and habitual behaviour and how they contextualise each other. We show that habits emerge naturally (and autodidactically) from sequential policy optimisation when agents are equipped with state-action policies. In active inference, behaviour has explorative (epistemic) and exploitative (pragmatic) aspects that are sensitive to ambiguity and risk respectively, where epistemic (ambiguity-resolving) behaviour enables pragmatic (reward-seeking) behaviour and the subsequent emergence of habits. Although goal-directed and habitual policies are usually associated with model based and model-free schemes, we find the more important distinction is between belief-free and belief-based schemes. The underlying (variational) belief updating provides a comprehensive (if metaphorical) process theory for several phenomena, including the transfer of dopamine responses, reversal learning, habit formation and devaluation. Finally, we show that active inference reduces to a classical (Bellman) scheme, in the absence of ambiguity. PMID- 27375279 TI - Molecular genetics of Leber congenital amaurosis in Chinese: New data from 66 probands and mutation overview of 159 probands. AB - Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophy. We have previously performed a mutational analysis of the known LCA associated genes in probands with LCA by both Sanger and whole exome sequencing. In this study, whole exome sequencing was carried out on 66 new probabds with LCA. In conjunction with these data, the present study provides a comprehensive analysis of the spectrum and frequency of all known genes associated with retinal dystrophy in a total of 159 Chinese probands with LCA. The known genes responsible for all forms hereditary retinal dystrophy were included based on information from RetNet. The candidate variants were filtered by bioinformatics analysis and confirmed by Sanger sequencing. Potentially causative mutations were further validated in available family members. Overall, a total of 118 putative pathogenic mutations from 23 genes were identified in 56.6% (90/159) of probands. These mutations were harbored in 13 LCA-associated genes and in ten genes related to other forms of retinal dystrophy. The most frequently mutated gene in probands with LCA was GUCY2D (10.7%, 17/159). A series of mutational analyses suggests that all known genes associated with retinal dystrophy account for 56.6% of Chinese patients with LCA. A comprehensive molecular genetic analysis of Chinese patients with LCA provides an overview of the spectrum and frequency of ethno specific mutations of all known genes, as well as indications about other unknown genes in the remaining probands who lacked identified mutations. PMID- 27375280 TI - The different effects of twin boundary and grain boundary on reducing tension compression yield asymmetry of Mg alloys. AB - In the present study, a coarse grained AZ31 plate was refined by twin boundaries (TBs) and grain boundaries (GBs), respectively. A comparative study about the different effects of grain refinements by GBs and by TBs on tension-compression yield asymmetry was performed. Our results show that both the refinements by GBs and by TBs increase the tensile and compressive yield strengths, but to a different degree. TBs are more effective to harden twinning, but yield a lower strengthening against prismatic slip, and a much lower tension-compression yield asymmetry is thus obtained. Both the differences in boundary coherence and misorientation between GBs and TBs affect the hardening. The misorientation of TBs provides a lower geometric compatibility factor (a higher hardening) for both prismatic slip and twinning than that of GBs, which in detail is the result of the much higher angle between c-axes of the two sides of TBs (about 86 degrees ) than GBs (0-50 degrees ). It is found that, for hardening of prismatic slip, boundary coherence plays a more important role than misorientation. With regard to twinning, the different misorientation of TBs from GBs mainly accounts for their different hardening effects. PMID- 27375281 TI - Conventional slow freezing cryopreserves mouflon spermatozoa better than vitrification. AB - This work examines the effectiveness of a TCG (Tris, citric acid, glucose, 6% egg yolk and 5% glycerol) and a TEST (TES, Tris, glucose, 6% egg yolk and 5% glycerol) sperm extender in the freezing of mouflon spermatozoa at slow cooling rates, using different pre-freezing equilibration times (2-3 hr). It also examines the tolerance of mouflon spermatozoa to different concentrations of cryoprotectants (5, 10, 20% glycerol; 5%, 10%, 20% dimethyl sulfoxide; 6% polyvinylpyrrolidone) and/or sucrose (100, 300, 500 mm). The highest quality (p < .01) thawed spermatozoa were obtained when using the TEST extender and an equilibration time of 3 hr. Sperm motility and membrane integrity were strongly reduced when using rapid freezing rates (60-85 degrees C min-1 ), independent of the concentration of cryoprotectants. The lowest sucrose concentration (100 mm) provided the highest (p < .05) percentage of motile spermatozoa and live spermatozoa with an intact acrosome. Vitrified-warmed sperm variables were at their best when the spermatozoa was diluted in TCG-6% egg yolk + 100 mm sucrose and warmed at 60 degrees C. Slow warming at 37 degrees C strongly reduced (p < .05) sperm motility and viability. However, sperm vitrification returned lower fertility, sperm motility and sperm viability values than conventional sperm freezing. PMID- 27375282 TI - Lymphadenopathy syndrome in systemic lupus erythematosus: Is it Kikuchi-Fujimoto disease? PMID- 27375283 TI - Long-term lamivudine therapy in chronic hepatitis B. AB - BACKGROUND: One to 5 years of therapy of chronic hepatitis B with oral nucleoside analogues result in significant clinical improvements, but effects of more prolonged therapy are not well defined. AIM: To describe outcomes of chronic hepatitis B with long-term lamivudine therapy. METHODS: Forty-two patients with chronic hepatitis B treated with lamivudine were followed for 3.2-19.5 (median = 16.1) years. Therapy was switched to other agents (n = 16) if patients developed lamivudine resistance and relapse of disease. RESULTS: Among 22 HBeAg-positive patients, 17 (77%) became HBeAg negative, of whom 5 (23%) subsequently cleared HBsAg. Among 20 HBeAg-negative patients, 10 (50%) cleared HBsAg. The time to HBsAg clearance ranged from 0.9 to 16.8 (median = 9.3) years. Lamivudine resistance arose in 24 patients (57%) of whom 6 (25%) lost HBsAg. HBsAg clearance was not always accompanied by seroconversion; anti-HBs appearing concurrently in only five patients (33%). Nevertheless, HBsAg loss allowed for stopping therapy in all patients, none re-developing HBsAg or suffering relapse; all having normal alanine aminotransferase levels and no (n = 13) or unquantifiable HBV DNA levels (n = 2) when last seen. In contrast, seven of 27 patients (26%) who remained HBsAg-positive died of liver disease or liver cancer or underwent liver transplantation, all of whom had cirrhosis. CONCLUSIONS: Long-term viral suppression with nucleoside analogues leads to HBsAg loss in a substantial proportion of patients, particularly if HBeAg-negative. Serious outcomes during the first 10-20 years of treatment occur largely among patients with pre-existing cirrhosis who do not clear HBsAg with therapy. PMID- 27375286 TI - The effects of implant topography on osseointegration under estrogen deficiency induced osteoporotic conditions: Histomorphometric, transcriptional and ultrastructural analysis. AB - Compromised bone quality and/or healing in osteoporosis are recognised risk factors for impaired dental implant osseointegration. This study examined the effects of (1) experimentally induced osteoporosis on titanium implant osseointegration and (2) the effect of modified implant surface topography on osseointegration under osteoporosis-like conditions. Machined and micro-roughened surface implants were placed into the maxillary first molar root socket of 64 ovariectomised and sham-operated Sprague-Dawley rats. Subsequent histological and SEM observations showed tissue maturation on the micro-rough surfaced implants in ovariectomised animals as early as 3days post-implantation. The degree of osseointegration was also significantly higher around the micro-rough implants in ovariectomised animals after 14days of healing although by day 28, similar levels of osseointegration were found for all test groups. The micro-rough implants significantly increased the early (day 3) gene expression of alkaline phosphatase, osteocalcin, receptor activator of nuclear factor kappa-B ligand and dentin matrix protein 1 in implant adherent cells. By day 7, the expression of inflammatory genes decreased while the expression of the osteogenic markers increased further although there were few statistically significant differences between the micro-rough and machined surfaces. Osteocyte morphology was also affected by estrogen deficiency with the size of the cells being reduced in trabecular bone. In conclusion, estrogen deficiency induced osteoporotic conditions negatively influenced the early osseointegration of machined implants while micro-rough implants compensated for these deleterious effects by enhancing osteogenic cell differentiation on the implant surface. STATEMENT OF SIGNIFICANCE: Lower bone density, poor bone quality and osseous microstructural changes are all features characteristic of osteoporosis that may impair the osseointegration of dental implants. Using a clinically relevant trabecular bone model in the rat maxilla, we demonstrated histologically that the negative effects of surgically-induced osteoporosis on osseointegration could be ameliorated by the biomaterial's surface topography. Furthermore, gene expression analysis suggests this may be a result of enhanced osteogenic cell differentiation on the implant surface. PMID- 27375288 TI - Achieving High Aqueous Energy Storage via Hydrogen-Generation Passivation. AB - A new design strategy for polyimides/carbon nanotube networks is reported, aiming to passivate the hydrogen-evolution mechanism on the molecular structures of electrodes, thus substantially boosting their aqueous energy-storage capabilities. The intrinsic sluggish hydrogen-evolution activity of polyimides is further passivated via Li(+) association during battery charging, leading to a much wider voltage window and exceptional energy-storage capability. PMID- 27375285 TI - Matrix directed adipogenesis and neurogenesis of mesenchymal stem cells derived from adipose tissue and bone marrow. AB - Mesenchymal stem cells (MSCs) can differentiate into multiple lineages through guidance from the biophysical and biochemical properties of the extracellular matrix. In this work we conduct a combinatorial study of matrix properties that influence adipogenesis and neurogenesis including: adhesion proteins, stiffness, and cell geometry, for mesenchymal stem cells derived from adipose tissue (AT MSCs) and bone marrow (BM-MSCs). We uncover distinct differences in integrin expression, the magnitude of traction stress, and lineage specification to adipocytes and neuron-like cells between cell sources. In the absence of media supplements, adipogenesis in AT-MSCs is not significantly influenced by matrix properties, while the converse is true in BM-MSCs. Both cell types show changes in the expression of neurogenesis markers as matrix cues are varied. When cultured on laminin conjugated microislands of the same adhesive area, BM-MSCs display elevated adipogenesis markers, while AT-MSCs display elevated neurogenesis markers; integrin analysis suggests neurogenesis in AT-MSCs is guided by adhesion through integrin alphavbeta3. Overall, the properties of the extracellular matrix guides MSC adhesion and lineage specification to different degrees and outcomes, in spite of their similarities in general characteristics. This work will help guide the selection of MSCs and matrix components for applications where high fidelity of differentiation outcome is desired. STATEMENT OF SIGNIFICANCE: Mesenchymal stem cells (MSCs) are an attractive cell type for stem cell therapies; however, in order for these cells to be useful in medicine, we need to understand how they respond to the physical and chemical environments of tissue. Here, we explore how two promising sources of MSCs-those derived from bone marrow and from adipose tissue-respond to the compliance and composition of tissue using model extracellular matrices. Our results demonstrate a source specific propensity to undergo adipogenesis and neurogenesis, and uncover a role for adhesion, and the degree of traction force exerted on the substrate in guiding these lineage outcomes. PMID- 27375287 TI - Risk and treatment effect heterogeneity: re-analysis of individual participant data from 32 large clinical trials. AB - Background: Risk of the outcome is a mathematical determinant of the absolute treatment benefit of an intervention, yet this can vary substantially within a trial population, complicating the interpretation of trial results. Methods: We developed risk models using Cox or logistic regression on a set of large publicly available randomized controlled trials (RCTs). We evaluated risk heterogeneity using the extreme quartile risk ratio (EQRR, the ratio of outcome rates in the lowest risk quartile to that in the highest) and skewness using the median to mean risk ratio (MMRR, the ratio of risk in the median risk patient to the average). We also examined heterogeneity of treatment effects (HTE) across risk strata. Results: We describe 39 analyses using data from 32 large trials, with event rates across studies ranging from 3% to 63% (median = 15%, 25th-75th percentile = 9-29%). C-statistics of risk models ranged from 0.59 to 0.89 (median = 0.70, 25th-75th percentile = 0.65-0.71). The EQRR ranged from 1.8 to 50.7 (median = 4.3, 25th-75th percentile = 3.0-6.1). The MMRR ranged from 0.4 to 1.0 (median = 0.86, 25th-75th percentile = 0.80-0.92). EQRRs were predictably higher and MMRRs predictably lower as the c-statistic increased or the overall outcome incidence decreased. Among 18 comparisons with a significant overall treatment effect, there was a significant interaction between treatment and baseline risk on the proportional scale in only one. The difference in the absolute risk reduction between extreme risk quartiles ranged from -3.2 to 28.3% (median = 5.1%; 25th-75th percentile = 0.3-10.9). Conclusions: There is typically substantial variation in outcome risk in clinical trials, commonly leading to clinically significant differences in absolute treatment effects Most patients have outcome risks lower than the trial average reflected in the summary result. Risk-stratified trial analyses are feasible and may be clinically informative, particularly when the outcome is predictable and uncommon. PMID- 27375290 TI - Use of electronic healthcare records to identify complex patients with atrial fibrillation for targeted intervention. AB - Background: Practice guidelines recommend anticoagulation therapy for patients with atrial fibrillation (AF) who have other risk factors putting them at an elevated risk of stroke. These patients remain undertreated, but, with increasing use of electronic healthcare records (EHRs), it may be possible to identify candidates for treatment. Objective: To test algorithms for identifying AF patients who also have known risk factors for stroke and major bleeding using EHR data. Materials and Methods: We evaluated the performance of algorithms using EHR data from the Partners Healthcare System at identifying AF patients and 16 additional conditions that are risk factors in the CHA 2 DS 2 -VASc and HAS-BLED risk scores for stroke and major bleeding. Algorithms were based on information contained in problem lists, billing codes, laboratory data, prescription data, vital status, and clinical notes. The performance of candidate algorithms in 1000 bootstrap resamples was compared to a gold standard of manual chart review by experienced resident physicians. Results: : Physicians reviewed 480 patient charts. For 11 conditions, the median positive predictive value (PPV) of the EHR derived algorithms was greater than 0.90. Although the PPV for some risk factors was poor, the median PPV for identifying patients with a CHA 2 DS 2 -VASc score >=2 or a HAS-BLED score >=3 was 1.00 and 0.92, respectively. Discussion: We developed and tested a set of algorithms to identify AF patients and known risk factors for stroke and major bleeding using EHR data. Algorithms such as these can be built into EHR systems to facilitate informed decision making and help shift population health management efforts towards patients with the greatest need. PMID- 27375289 TI - COPS5 amplification and overexpression confers tamoxifen-resistance in ERalpha positive breast cancer by degradation of NCoR. AB - Oestrogen receptor alpha (ERalpha) antagonists are used in endocrine therapies for ERalpha-positive (ERalpha+) breast cancer patients. Unfortunately the clinical benefit is limited due to intrinsic and acquired drug resistance. Here using integrated genomic and functional studies, we report that amplification and/or overexpression of COPS5 (CSN5/JAB1) confers resistance to tamoxifen. Amplification and overexpression of COPS5, a catalytic subunit of the COP9 complex, is present in about 9% of the ERalpha+ primary breast cancer and more frequently (86.7%, 26/30) in tamoxifen-refractory tumours. Overexpression of COPS5, through its isopeptidase activity, leads to ubiquitination and proteasome mediated degradation of NCoR, a key corepressor for ERalpha and tamoxifen mediated suppression of ERalpha target genes. Importantly, COPS5 overexpression causes tamoxifen-resistance in preclinical breast cancer models in vitro and in vivo. We also demonstrate that genetic inhibition of the isopeptidase activity of COPS5 is sufficient to re-sensitize the resistant breast cancer cells to tamoxifen-treatment, offering a potential therapeutic approach for endocrine resistant breast cancer patients. PMID- 27375291 TI - Two-year longitudinal assessment of physicians' perceptions after replacement of a longstanding homegrown electronic health record: does a J-curve of satisfaction really exist? AB - This report describes a 2-year prospective, longitudinal survey of attending physicians in 3 clinical areas (family medicine, general pediatrics, internal medicine) who experienced a transition from a homegrown electronic health record (EHR) to a vendor EHR. Participants were already highly familiar with using EHRs. Data were collected 1 month before and 3, 6, 13, and 25 months post implementation. Our primary goal was to determine if perceptions followed a J curve pattern in which they initially dropped but eventually surpassed baseline measures. A J-curve was not found for any measures, including workflow, safety, communication, and satisfaction. Only the reminders and alerts measure dropped and then returned to baseline (U-curve); a few remained flatlined. Most dropped and remained below baseline (L-curve). The only measure that remained above baseline was documenting in the exam room with the patient. This study adds to the literature about current controversies surrounding EHR adoption and physician satisfaction. PMID- 27375292 TI - A framework for evaluating electronic health record vendor user-centered design and usability testing processes. AB - Objective: Currently, there are few resources for electronic health record (EHR) purchasers and end users to understand the usability processes employed by EHR vendors during product design and development. We developed a framework, based on human factors literature and industry standards, to systematically evaluate the user-centered design processes and usability testing methods used by EHR vendors. Materials and Methods: We reviewed current usability certification requirements and the human factors literature to develop a 15-point framework for evaluating EHR products. The framework is based on 3 dimensions: user-centered design process, summative testing methodology, and summative testing results. Two vendor usability reports were retrieved from the Office of the National Coordinator's Certified Health IT Product List and were evaluated using the framework. Results: One vendor scored low on the framework (5 pts) while the other vendor scored high on the framework (15 pts). The 2 scored vendor reports demonstrate the framework's ability to discriminate between the variabilities in vendor processes and to determine which vendors are meeting best practices. Discussion: The framework provides a method to more easily comprehend EHR vendors' usability processes and serves to highlight where EHR vendors may be falling short in terms of best practices. The framework provides a greater level of transparency for both purchasers and end users of EHRs. Conclusion: The framework highlights the need for clearer certification requirements and suggests that the authorized certification bodies that examine vendor usability reports may need to be provided with clearer guidance. PMID- 27375293 TI - The electronic health record audit file: the patient is waiting. AB - Objective: We describe how electronic health record (EHR) audit files can be used to understand how time is spent in primary care (PC). Materials/methods: We used audit file data from the Geisinger Clinic to quantify elements of the clinical workflow and to determine how these times vary by patient and encounter factors. We randomly selected audit file records representing 36 437 PC encounters across 26 clinic locations. Audit file data were used to estimate duration and variance of: (1) time in the waiting room, (2) nurse time with the patient, (3) time in the exam room without a nurse or physician, and (4) physician time with the patient. Multivariate modeling was used to test for differences by patient and by encounter features. Results: On average, a PC encounter took 54.6 minutes, with 5 minutes of nurse time, 15.5 minutes of physician time, and the remaining 62% of the time spent waiting to see a clinician or check out. Older age, female sex, and chronic disease were associated with longer wait times and longer time with clinicians. Level of service and numbers of medications, procedures, and lab orders were associated with longer time with clinicians. Late check-in and same day visits were associated with shorter wait time and clinician time. Conclusions: This study provides insights on uses of audit file data for workflow analysis during PC encounters. Discussion: Scalable ways to quantify clinical encounter workflow elements may provide the means to develop more efficient approaches to care and improve the patient experience. PMID- 27375294 TI - Partial Life History of Chrysodeixis includens (Lepidoptera: Noctuidae) on Summer Hosts. AB - The soybean looper, Chrysodeixis includens (Walker) (Lepidoptera: Noctuidae), is a major defoliating pest of soybeans, Glycine max (L.) Merrill, in Louisiana. However, other alternate host crops in the agroecosystem have the potential to impact C. includens populations. Life table statistics of C. includens on four host plants were evaluated. C. includens larvae were fed leaves of three cotton Gossypium hirsutum L. cultivars 'DP 143 B2RF,' 'DP 174 RF,' and 'PHY 485 WRF'; cowpea Vigna unguiculata (L.) Walpers 'California Blackeye'; three soybean cultivars 'Lyon,' 'PI 227687,' and 'RC 4955'; and sweetpotato Ipomoea batatas (L.) Lamarck 'Evangeline.' All C. includens larvae reared on cotton cultivars DP 143 B2RF and PHY 485 WRF experienced 100% mortality during the first instar. Total developmental period of preadult C. includens was significantly shorter on cotton DP 174 RF and cowpea California Blackeye but longer on sweetpotato Evangeline. Sweetpotato Evangeline had the highest amount of leaf tissue consumed and soybean Lyon had the least. Pupal weight was highest when insects fed on cotton DP 174 RF and lowest on soybean PI 227687. Life table statistics showed that the highest intrinsic rate of increase and net reproductive rate were attained when insects were reared on cotton DP 174 RF and cowpea California Blackeye whilst the lowest were recorded on soybean PI 227687. This study provides valuable information on the role of alternative host crops on the partial life history of C. includens in Louisiana agroecosystems. PMID- 27375295 TI - Strategies to improve phase-stability of ultrafast swept source optical coherence tomography for single shot imaging of transient mechanical waves at 16 kHz frame rate. AB - We present single-shot phase-sensitive imaging of propagating mechanical waves within tissue, enabled by an ultrafast optical coherence tomography (OCT) system powered by a 1.628 MHz Fourier domain mode-locked (FDML) swept laser source. We propose a practical strategy for phase-sensitive measurement by comparing the phases between adjacent OCT B-scans, where the B-scan contains a number of A scans equaling an integer number of FDML buffers. With this approach, we show that micro-strain fields can be mapped with ~3.0 nm sensitivity at ~16 000 fps. The system's capabilities are demonstrated on porcine cornea by imaging mechanical wave propagation launched by a pulsed UV laser beam, promising non contact, real-time, and high-resolution optical coherence elastography. PMID- 27375296 TI - Self-aligned grating couplers on template-stripped metal pyramids via nanostencil lithography. AB - We combine nanostencil lithography and template stripping to create self-aligned patterns about the apex of ultrasmooth metal pyramids with high throughput. Three dimensional patterns such as spiral and asymmetric linear gratings, which can couple incident light into a hot spot at the tip, are presented as examples of this fabrication method. Computer simulations demonstrate that spiral and linear diffraction grating patterns are both effective at coupling light to the tip. The self-aligned stencil lithography technique can be useful for integrating plasmonic couplers with sharp metallic tips for applications such as near-field optical spectroscopy, tip-based optical trapping, plasmonic sensing, and heat assisted magnetic recording. PMID- 27375297 TI - A structure of CdS/CuxS quantum dots sensitized solar cells. AB - This work introduces a type of CdS/CuxS quantum dots (QDs) as sensitizers in quantum dot sensitized solar cells by in-situ cationic exchange reaction method where CdS photoanode is directly immersed in CuCl2 methanol solution to replace Cd2+ by Cu2+. The p-type CuxS layer on the surface of the CdS QDs can be considered as hole transport material, which not only enhances the light harvesting of photoanode but also boosts the charge separation after photo excitation. Therefore, both the electron collection efficiency and power conversion efficiency of the solar cell are improved from 80% to 92% and from 1.21% to 2.78%, respectively. PMID- 27375298 TI - Switching 70Pb(Mg1/3Nb2/3)O3-0.30PbTiO3 single crystal by 3 MHz bipolar field. AB - Polarization switching and associated electromechanical property changes at 3.0 MHz were investigated with and without a direct current (dc) bias for [001]c poled 0.70Pb(Mg1/3Nb2/3)O3-0.30PbTiO3 single crystal. The results showed that the coercive field under a bipolar pulse at 3.0 MHz is 2.75 times as large as conventional defined Ec (2.58 kV/cm at 0.1 Hz), and a dc bias can further enlarge the driving field. Our results point to an innovative transducer operating mechanism at high frequencies since one could drive the crystal under much larger fields at high frequencies to produce much stronger signals from a small array element for deeper penetration imaging. PMID- 27375301 TI - NEW IMPROVEMENTS TO MFIRE TO ENHANCE FIRE MODELING CAPABILITIES. AB - NIOSH's mine fire simulation program, MFIRE, is widely accepted as a standard for assessing and predicting the impact of a fire on the mine ventilation system and the spread of fire contaminants in coal and metal/nonmetal mines, which has been used by U.S. and international companies to simulate fires for planning and response purposes. MFIRE is a dynamic, transient-state, mine ventilation network simulation program that performs normal planning calculations. It can also be used to analyze ventilation networks under thermal and mechanical influence such as changes in ventilation parameters, external influences such as changes in temperature, and internal influences such as a fire. The program output can be used to analyze the effects of these influences on the ventilation system. Since its original development by Michigan Technological University for the Bureau of Mines in the 1970s, several updates have been released over the years. In 2012, NIOSH completed a major redesign and restructuring of the program with the release of MFIRE 3.0. MFIRE's outdated FORTRAN programming language was replaced with an object-oriented C++ language and packaged into a dynamic link library (DLL). However, the MFIRE 3.0 release made no attempt to change or improve the fire modeling algorithms inherited from its previous version, MFIRE 2.20. This paper reports on improvements that have been made to the fire modeling capabilities of MFIRE 3.0 since its release. These improvements include the addition of fire source models of the t-squared fire and heat release rate curve data file, the addition of a moving fire source for conveyor belt fire simulations, improvement of the fire location algorithm, and the identification and prediction of smoke rollback phenomena. All the improvements discussed in this paper will be termed as MFIRE 3.1 and released by NIOSH in the near future. PMID- 27375299 TI - Biosynthetic Polymers as Functional Materials. AB - The synthesis of functional polymers encoded with biomolecules has been an extensive area of research for decades. As such, a diverse toolbox of polymerization techniques and bioconjugation methods has been developed. The greatest impact of this work has been in biomedicine and biotechnology, where fully synthetic and naturally derived biomolecules are used cooperatively. Despite significant improvements in biocompatible and functionally diverse polymers, our success in the field is constrained by recognized limitations in polymer architecture control, structural dynamics, and biostabilization. This Perspective discusses the current status of functional biosynthetic polymers and highlights innovative strategies reported within the past five years that have made great strides in overcoming the aforementioned barriers. PMID- 27375300 TI - RAFT Aqueous Dispersion Polymerization of N-(2 (Methacryloyloxy)ethyl)pyrrolidone: A Convenient Low Viscosity Route to High Molecular Weight Water-Soluble Copolymers. AB - RAFT solution polymerization of N-(2-(methacryoyloxy)ethyl)pyrrolidone (NMEP) in ethanol at 70 degrees C was conducted to produce a series of PNMEP homopolymers with mean degrees of polymerization (DP) varying from 31 to 467. Turbidimetry was used to assess their inverse temperature solubility behavior in dilute aqueous solution, with an LCST of approximately 55 degrees C being observed in the high molecular weight limit. Then a poly(glycerol monomethacylate) (PGMA) macro-CTA with a mean DP of 63 was chain-extended with NMEP using a RAFT aqueous dispersion polymerization formulation at 70 degrees C. The target PNMEP DP was systematically varied from 100 up to 6000 to generate a series of PGMA63-PNMEP x diblock copolymers. High conversions (>=92%) could be achieved when targeting up to x = 5000. GPC analysis confirmed high blocking efficiencies and a linear evolution in Mn with increasing PNMEP DP. A gradual increase in Mw/Mn was also observed when targeting higher DPs. However, this problem could be minimized (Mw/Mn < 1.50) by utilizing a higher purity grade of NMEP (98% vs 96%). This suggests that the broader molecular weight distributions observed at higher DPs are simply the result of a dimethacrylate impurity causing light branching, rather than an intrinsic side reaction such as chain transfer to polymer. Kinetic studies confirmed that the RAFT aqueous dispersion polymerization of NMEP was approximately four times faster than the RAFT solution polymerization of NMEP in ethanol when targeting the same DP in each case. This is perhaps surprising because both 1H NMR and SAXS studies indicate that the core-forming PNMEP chains remain relatively solvated at 70 degrees C in the latter formulation. Moreover, dissolution of the initial PGMA63-PNMEP x particles occurs on cooling from 70 to 20 degrees C as the PNMEP block passes through its LCST. Hence this RAFT aqueous dispersion polymerization formulation offers an efficient route to a high molecular weight water-soluble polymer in a rather convenient low-viscosity form. Finally, the relatively expensive PGMA macro-CTA was replaced with a poly(methacrylic acid) (PMAA) macro-CTA. High conversions were also achieved for PMAA85-PNMEP x diblock copolymers prepared via RAFT aqueous dispersion polymerization for x <= 4000. Again, better control was achieved when using the 98% purity NMEP monomer in such syntheses. PMID- 27375302 TI - Retention of phytosiderophores by the soil solid phase - adsorption and desorption. AB - BACKGROUND AND AIMS: Graminaceous plants exude phytosiderophores (PS) for acquiring Fe. Adsorption of PS and its metal complexes to the soil solid phase reduces the FePS solution concentration and hence Fe uptake. In this study we aimed to quantify adsorption, and to determine to what extent adsorption depends on the complexed metal and on soil properties. Furthermore, we examined if adsorption is a reversible process. METHODS: Adsorption and desorption of PS and metal-PS complexes were examined in batch experiments in which the PS 2' deoxymugineic acid (DMA) and its metal-complexes (FeDMA, CuDMA, NiDMA and ZnDMA) interacted with several calcareous soils. RESULTS: Adsorption of DMA ligand (0 1000 MUM) and metal-DMA complexes (0-100 MUM) was linear in the concentration range examined. Adsorption varied by a factor ~2 depending on the complexed metal and by up to a factor 3.5 depending on the soil. Under field-like conditions (50 % water holding capacity), 50-84 % of the DMA was predicted to be retained to the soil solid phase. Alike adsorption, desorption of metal-DMA complexes is fast (approximate equilibrium within 1 hour). However, only a small fraction of the adsorbed FeDMA (28-35 %) could be desorbed. CONCLUSIONS: Despite this small fraction, the desorbed FeDMA still exceeded the amount in solution, indicating that desorption of FeDMA from soil reactive compounds can be an important process buffering the solution concentration. PMID- 27375303 TI - International Charitable Connections: the Growth in Number, and the Countries of Operation, of English and Welsh Charities Working Overseas. AB - This paper provides new empirical evidence about English and Welsh charities operating internationally. It answers basic questions unaddressed in existing work: how many charities work overseas, and how has this number changed over time? In which countries do they operate, and what underlies these geographical patterns? It makes use of a unique administrative dataset which records every country in which each charity operates. The results show a sizeable increase in the number of charities working overseas since the mid-1990s. They show that charities are much more likely to work in countries with colonial and linguistic ties to the UK, and less likely to work in countries with high levels of instability or corruption. This considerable geographical unevenness, even after controlling for countries' population size and poverty, illustrates the importance of supply-side theories and of institutional factors to an understanding of international voluntary activity. The paper also serves to provide a new perspective on international charitable operation: while it is the large development charities that are household names, the results reveal the extent of small-scale 'grassroots' registered charitable activity that links people and places internationally, and the extent of activity in 'developed' as well as 'developing' country contexts. PMID- 27375304 TI - Payday lending in the UK: the regul(aris)ation of a necessary evil? AB - Concern about the increasing use of payday lending led the UK's Financial Conduct Authority to introduce landmark reforms in 2014/15. While these reforms have generally been welcomed as a way of curbing 'extortionate' and 'predatory' lending, this paper presents a more nuanced picture based on a theoretically informed analysis of the growth and nature of payday lending combined with original and rigorous qualitative interviews with customers. We argue that payday lending has grown as a result of three major and inter-related trends: growing income insecurity for people both in and out of work; cuts in state welfare provision; and increasing financialisation. Recent reforms of payday lending do nothing to tackle these root causes. Our research also makes a major contribution to debates about the 'everyday life' of financialisation by focusing on the 'lived experience' of borrowers. We show that, contrary to the rather simplistic picture presented by the media and many campaigners, various aspects of payday lending are actually welcomed by customers, given the situations they are in. Tighter regulation may therefore have negative consequences for some. More generally, we argue that the regul(aris)ation of payday lending reinforces the shift in the role of the state from provider/redistributor to regulator/enabler. PMID- 27375305 TI - LINKING SURVEY AND ADMINISTRATIVE RECORDS: MECHANISMS OF CONSENT. AB - Survey records are increasingly being linked to administrative databases to enhance the survey data and increase research opportunities for data users. A necessary prerequisite to linking survey and administrative records is obtaining informed consent from respondents. Obtaining consent from all respondents is a difficult challenge and one that faces significant resistance. Consequently, data linkage consent rates vary widely from study-to-study. Several studies have found significant differences between consenters and non-consenters on socio demographic variables, but no study has investigated the underlying mechanisms of consent from a theory-driven perspective. In this study, we describe and test several hypotheses related to respondents' willingness to consent to an earnings and benefit data linkage request based on mechanisms related to financial uncertainty, privacy concerns, resistance towards the survey interview, level of attentiveness during the interview, the respondents' preexisting relationship with the administrative data agency, and matching respondents and interviewers on observable characteristics. The results point to several implications for survey practice and suggestions for future research. PMID- 27375306 TI - Depression and Co-Occurring Health Determinants of Hispanic Men with HIV Infection in the U.S.-Mexico Border Region: A Pilot Study. AB - HIV infection among Hispanic men is a public health concern. Certain factors have been identified that may contribute to the high rates of HIV infection among Hispanic men such as migration, acculturation, poverty, and depression. Hispanic men with HIV infection are at risk for additional co-occurring health issues. Given limited research few studies have focused specifically on Hispanic men with HIV infection residing in a U.S.-Mexico border community. This pilot study surveyed participants (n = 39), to better understand co-occurrence of health determinants, especially depression among Hispanic men with HIV infection. The study's findings indicate that clinicians need to be aware that factors may influence depression among people with Hispanic men with HIV infection. Clinicians also need awareness of the impact of depression on adherence to HIV care and treatment among Hispanic men with HIV infection. More research is needed to explore the relationship of HIV-related stigma, HIV disclosure, social support, and depression among Hispanic men with HIV infection. PMID- 27375307 TI - On point estimation of the abnormality of a Mahalanobis index. AB - Mahalanobis distance may be used as a measure of the disparity between an individual's profile of scores and the average profile of a population of controls. The degree to which the individual's profile is unusual can then be equated to the proportion of the population who would have a larger Mahalanobis distance than the individual. Several estimators of this proportion are examined. These include plug-in maximum likelihood estimators, medians, the posterior mean from a Bayesian probability matching prior, an estimator derived from a Taylor expansion, and two forms of polynomial approximation, one based on Bernstein polynomial and one on a quadrature method. Simulations show that some estimators, including the commonly-used plug-in maximum likelihood estimators, can have substantial bias for small or moderate sample sizes. The polynomial approximations yield estimators that have low bias, with the quadrature method marginally to be preferred over Bernstein polynomials. However, the polynomial estimators sometimes yield infeasible estimates that are outside the 0-1 range. While none of the estimators are perfectly unbiased, the median estimators match their definition; in simulations their estimates of the proportion have a median error close to zero. The standard median estimator can give unrealistically small estimates (including 0) and an adjustment is proposed that ensures estimates are always credible. This latter estimator has much to recommend it when unbiasedness is not of paramount importance, while the quadrature method is recommended when bias is the dominant issue. PMID- 27375308 TI - Determination of 241Am in Urine Using Sector Field Inductively Coupled Plasma Mass Spectrometry (SF-ICP-MS). AB - Quantification of 241Am in urine at low levels is important for assessment of individuals' or populations' accidental, environmental, or terrorism-related internal contamination, but no convenient, precise method has been established to rapidly determine these low levels. Here we report a new analytical method to measure 241Am as developed and validated at the Centers for Disease Control and Prevention (CDC) by means of the selective retention of Am from urine directly on DGA resin, followed by SF-ICP-MS detection. The method provides rapid results with a Limit of Detection (LOD) of 0.22 pg/L (0.028 Bq/L), which is lower than 1/3 of the C/P CDG for 241Am at 5 days post-exposure. The results obtained by this method closely agree with CDC values as measured by Liquid Scintillation Counting, and with National Institute of Standards Technology (NIST) Certified Reference Materials (CRM) target values. PMID- 27375309 TI - Summary report MTAA14-NAMLS11. PMID- 27375310 TI - Automation system for neutron activation analysis at the reactor IBR-2, Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Dubna, Russia. AB - The present status of development of software packages and equipment designed for automation of NAA at the reactor IBR-2 of FLNP, JINR, Dubna, RF, is described. The NAA database, construction of sample changers and software for automation of spectra measurement and calculation of concentrations are presented. Automation of QC procedures is integrated in the software developed. Details of the design are shown. PMID- 27375311 TI - Detection limits should be a thing of the past in gamma-ray spectrometry in general as well as in neutron activation analysis. AB - In gamma-ray spectrometry with high-resolution detectors, full-energy peaks are often to be detected by a peak-search algorithm, with a threshold for detection. Detection limits can be derived from this. Detection limits are often computed along with measured activities or concentrations. When an analyte is not detected, the detection limit remains as the only available information. This leads to inhomogeneous datasets that are difficult or impossible to process correctly without introducing artefacts or biases. Here, it is proposed to determine peak areas at predetermined energies. An unbiased result with its uncertainty always results, obviating the "detection limit" concept. PMID- 27375312 TI - Increased yield stability of field-grown winter barley (Hordeum vulgare L.) varietal mixtures through ecological processes. AB - Crop variety mixtures have the potential to increase yield stability in highly variable and unpredictable environments, yet knowledge of the specific mechanisms underlying enhanced yield stability has been limited. Ecological processes in genetically diverse crops were investigated by conducting field trials with winter barley varieties (Hordeum vulgare), grown as monocultures or as three-way mixtures in fungicide treated and untreated plots at three sites. Mixtures achieved yields comparable to the best performing monocultures whilst enhancing yield stability despite being subject to multiple predicted and unpredicted abiotic and biotic stresses including brown rust (Puccinia hordei) and lodging. There was compensation through competitive release because the most competitive variety overyielded in mixtures thereby compensating for less competitive varieties. Facilitation was also identified as an important ecological process within mixtures by reducing lodging. This study indicates that crop varietal mixtures have the capacity to stabilise productivity even when environmental conditions and stresses are not predicted in advance. Varietal mixtures provide a means of increasing crop genetic diversity without the need for extensive breeding efforts. They may confer enhanced resilience to environmental stresses and thus be a desirable component of future cropping systems for sustainable arable farming. PMID- 27375313 TI - A geometric calibration method for inverse geometry computed tomography using P matrices. AB - Accurate and artifact free reconstruction of tomographic images requires precise knowledge of the imaging system geometry. This work proposes a novel projection matrix (P-matrix) based calibration method to enable C-arm inverse geometry CT (IGCT). The method is evaluated for scanning-beam digital x-ray (SBDX), a C-arm mounted inverse geometry fluoroscopic technology. A helical configuration of fiducials is imaged at each gantry angle in a rotational acquisition. For each gantry angle, digital tomosynthesis is performed at multiple planes and a composite image analogous to a cone-beam projection is generated from the plane stack. The geometry of the C-arm, source array, and detector array is determined at each angle by constructing a parameterized 3D-to-2D projection matrix that minimizes the sum-of-squared deviations between measured and projected fiducial coordinates. Simulations were used to evaluate calibration performance with translations and rotations of the source and detector. In a geometry with 1 mm translation of the central ray relative to the axis-of-rotation and 1 degree yaw of the detector and source arrays, the maximum error in the recovered translational parameters was 0.4 mm and maximum error in the rotation parameter was 0.02 degrees. The relative root-mean-square error in a reconstruction of a numerical thorax phantom was 0.4% using the calibration method, versus 7.7% without calibration. Changes in source-detector-distance were the most challenging to estimate. Reconstruction of experimental SBDX data using the proposed method eliminated double contour artifacts present in a non-calibrated reconstruction. The proposed IGCT geometric calibration method reduces image artifacts when uncertainties exist in system geometry. PMID- 27375314 TI - Method for dose-reduced 3D catheter tracking on a scanning-beam digital x-ray system using dynamic electronic collimation. AB - Scanning-beam digital x-ray (SBDX) is an inverse geometry x-ray fluoroscopy system capable of tomosynthesis-based 3D catheter tracking. This work proposes a method of dose-reduced 3D tracking using dynamic electronic collimation (DEC) of the SBDX scanning x-ray tube. Positions in the 2D focal spot array are selectively activated to create a region-of-interest (ROI) x-ray field around the tracked catheter. The ROI position is updated for each frame based on a motion vector calculated from the two most recent 3D tracking results. The technique was evaluated with SBDX data acquired as a catheter tip inside a chest phantom was pulled along a 3D trajectory. DEC scans were retrospectively generated from the detector images stored for each focal spot position. DEC imaging of a catheter tip in a volume measuring 11.4 cm across at isocenter required 340 active focal spots per frame, versus 4473 spots in full-FOV mode. The dose-area-product (DAP) and peak skin dose (PSD) for DEC versus full field-of-view (FOV) scanning were calculated using an SBDX Monte Carlo simulation code. DAP was reduced to 7.4% to 8.4% of the full-FOV value, consistent with the relative number of active focal spots (7.6%). For image sequences with a moving catheter, PSD was 33.6% to 34.8% of the full-FOV value. The root-mean-squared-deviation between DEC-based 3D tracking coordinates and full-FOV 3D tracking coordinates was less than 0.1 mm. The 3D distance between the tracked tip and the sheath centerline averaged 0.75 mm. Dynamic electronic collimation can reduce dose with minimal change in tracking performance. PMID- 27375315 TI - Hierarchical nucleus segmentation in digital pathology images. AB - Extracting nuclei is one of the most actively studied topic in the digital pathology researches. Most of the studies directly search the nuclei (or seeds for the nuclei) from the finest resolution available. While the richest information has been utilized by such approaches, it is sometimes difficult to address the heterogeneity of nuclei in different tissues. In this work, we propose a hierarchical approach which starts from the lower resolution level and adaptively adjusts the parameters while progressing into finer and finer resolution. The algorithm is tested on brain and lung cancers images from The Cancer Genome Atlas data set. PMID- 27375316 TI - Factors Affecting Morbidity in Solid Organ Injuries. AB - Background and Aim. The aim of this study was to investigate the effects of demographic characteristics, biochemical parameters, amount of blood transfusion, and trauma scores on morbidity in patients with solid organ injury following trauma. Material and Method. One hundred nine patients with solid organ injury due to abdominal trauma during January 2005 and October 2015 were examined retrospectively in the General Surgery Department of Dicle University Medical Faculty. Patients' age, gender, trauma interval time, vital status (heart rate, arterial tension, and respiratory rate), hematocrit (HCT) value, serum area aminotransferase (ALT) and aspartate aminotransferase (AST) values, presence of free abdominal fluid in USG, trauma mechanism, extra-abdominal system injuries, injured solid organs and their number, degree of injury in abdominal CT, number of blood transfusions, duration of hospital stay, time of operation (for those undergoing operation), trauma scores (ISS, RTS, Glasgow coma scale, and TRISS), and causes of morbidity and mortality were examined. In posttraumatic follow-up period, intra-abdominal hematoma infection, emboli, catheter infection, and deep vein thrombosis were monitored as factors of morbidity. Results. One hundred nine patients were followed up and treated due to isolated solid organ injury following abdominal trauma. There were 81 males (74.3%) and 28 females (25.7%), and the mean age was 37.6 +/- 18.28 (15-78) years. When examining the mechanism of abdominal trauma in patients, the following results were obtained: 58 (53.3%) traffic accidents (22 out-vehicle and 36 in-vehicle), 27 (24.7%) falling from a height, 14 (12.9%) assaults, 5 (4.5%) sharp object injuries, and 5 (4.5%) gunshot injuries. When evaluating 69 liver injuries scaled by CT the following was detected: 14 (20.3%) of grade I, 32 (46.4%) of grade II, 22 (31.8%) of grade III, and 1 (1.5%) of grade IV. In 63 spleen injuries scaled by CT the following was present: grade I in 21 (33.3%), grade II in 27 (42.9%), grade III in 11 (17.5%), and grade IV in 4 (6.3%). The mean length of hospital stay after trauma was 6.46 days in the medically followed patients. This ratio was 8.13 days in 22 patients with morbidity and 5.98 days in 78 patients without morbidity. There was a morbidity in 22 (22%) patients medically followed after trauma. In this study, nonoperative treatment was observed to be performed safely in solid organ injuries after trauma in case of absence of hemodynamic stability and peritoneal irritation. It has been emphasized that injury of both liver and spleen (p < 0.01), high respiratory rate (p < 0.01), trauma scores (GKS, ISS, RTS) (p < 0.0001), and elevation of ALT AST values (p < 0.01) are stimulants for morbidity that may occur during follow-up. Conclusion. Medical follow-up can be considered in patients with high grade injuries similar to patients with low-grade solid organ injury after trauma. The injury of both liver and spleen, high respiratory rate, high GCS and ISS, low RTS, and elevation of ALT AST values were found to increase morbidity again in the follow-up of these patients. PMID- 27375317 TI - Regeneration of the power performance of cathodes affected by biofouling. AB - Air cathode microbial fuel cells (MFCs) were used in a cascade-system, to treat neat human urine as the fuel. Their long-term operation caused biodeterioration and biofouling of the cathodes. The cathodes were made from two graphite-painted layers, separated by a current collector. The initial performance of the MFCs was reaching average values of 105.5 +/- 32.2 MUW and current of 1164.5 +/- 120.2 MUA. After 3 months of operation the power performance decreased to 9.8 +/- 3.5 MUW, whilst current decreased to 461.2 +/- 137.5 MUA. Polarisation studies revealed significant transport losses accompanied by a biofilm formation on the cathodes. The alkaline lysis procedure was established to remove the biomass and chemical compounds adsorbed on the cathode's surface. As a result, the current increased from 378.6 +/- 108.3 MUA to 503.8 +/- 95.6 MUA. The additional step of replacing the outer layer of the cathode resulted in a further increase of current to 698.1 +/- 130 MUA. Similarly, the power performance of the MFCs was recovered to the original level reaching 105.3 +/- 16.3 MUW, which corresponds to 100% recovery. Monitoring bacterial cell number on the cathode's surface showed that biofilm formed during operation was successfully removed and composed mainly of dead bacterial cells after treatment. To the best of the authors' knowledge, this is the first time that the performance of deteriorating cathodes, has been successfully recovered for MFCs in-situ. Through this easy, fast and inexpensive procedure, designing multilayer cathodes may help enhance the range of operating conditions, if a biofilm forms on their surface. PMID- 27375318 TI - Analysing reduced tillage practices within a bio-economic modelling framework. AB - Sustainable intensification of agricultural production systems will require changes in farm practice. Within arable cropping systems, reducing the intensity of tillage practices (e.g. reduced tillage) potentially offers one such sustainable intensification approach. Previous researchers have tended to examine the impact of reduced tillage on specific factors such as yield or weed burden, whilst, by definition, sustainable intensification necessitates a system-based analysis approach. Drawing upon a bio-economic optimisation model, 'MEETA', we quantify trade-off implications between potential yield reductions, reduced cultivation costs and increased crop protection costs. We extend the MEETA model to quantify farm-level net margin, in addition to quantifying farm-level gross margin, net energy, and greenhouse gas emissions. For the lowest intensity tillage system, zero tillage, results demonstrate financial benefits over a conventional tillage system even when the zero tillage system includes yield penalties of 0-14.2% (across all crops). Average yield reductions from zero tillage literature range from 0 to 8.5%, demonstrating that reduced tillage offers a realistic and attainable sustainable intensification intervention, given the financial and environmental benefits, albeit that yield reductions will require more land to compensate for loss of calories produced, negating environmental benefits observed at farm-level. However, increasing uptake of reduced tillage from current levels will probably require policy intervention; an extension of the recent changes to the CAP ('Greening') provides an opportunity to do this. PMID- 27375319 TI - Correlation of Intra Vascular Cannula Insertion Technique and Ward Practices with Local Site Infection. AB - BACKGROUND: Peripheral intravascular cannulas are indispensable in modern day medical care. These cannulas, if not inserted properly, predispose a patient to various morbidities. The present study was carried out to assess the incidence of intravascular cannula associated infections and correlate it with cannula insertion techniques and ward practices. METHODS: The study was carried out in the wards of a tertiary care hospital. The study was divided into two phases, each phase comprising of 50 patients. In phase 1, cannula insertion was carried out after normal ward cleaning practices. In phase 2, cleaning of the site was done by standard surgical cleaning procedure. The cannula samples after removal were cultured and local signs of thrombophlebitis looked for at the site of insertion. Thrombophlebitis was considered a surrogate marker of local infection in the vessel wall. RESULT: The relative risk of acquiring thrombophlebitis increased by 2.18 times (applying univariate analysis) by existing methods as compared to the standard method. CONCLUSION: Use of standard cleaning protocol had a significant effect on decreasing the incidence of cannula associated infections and cannula related morbidity. PMID- 27375320 TI - Irritant Dermatitis to Staphylinid Beetle in Indian Troops in Congo. AB - BACKGROUND: Contact dermatitis to Staphylinid beetle is a well known entity worldwide. Paederus sabaeus (Econda) species of this insect was responsible for a widespread occurrence of this dermatitis in United Nations (UN) troops posted in Congo. This study was undertaken to observe the various aspects of this unique dermatitis in the mission area. METHODS: All clinically diagnosed cases of contact dermatitis to Econda occurring in Indian troops posted to UN mission in Congo during the study period were included. Their epidemiological and clinical characteristics with treatment options were studied in detail. RESULT: A wide range of dermatological manifestations were seen in the subjects under study. Few of the manifestations observed in the study have not been reported earlier in literature. Most of the reactions occurred on the exposed areas. Treatment options were guided by the site and the severity of the reaction. CONCLUSION: Contact dermatitis to Staphylinid beetle can mimic various other dermatoses and has to be considered in the differential diagnosis in all dermatological consultations during the peak season in the Congo mission area. The insect was found to have certain definite behavioural patterns, the knowledge of which would help in preventing this dermatosis. PMID- 27375321 TI - Evaluation of Vitreous Substitutes in Managing Complicated Vitreo-retinal Surgeries. AB - BACKGROUND: Vitreous substitutes presently in use for intraoperative tamponade are perfluorocarbon liquids (PFCL) and for post operative tamponade are silicon oil (SO), sulphur hexafluoride (SF6) and perfluorocarbon gas (PFC). Several factors are important for a thorough understanding of each of these vitreous substitutes. The absorption or necessity for removal, indications for use (including clinical studies and special surgical methods), additives and complications of use have to be considered. METHODS: Three port standard pars plana vitrectomy was performed in 60 consecutive cases requiring intra-vitreal intervention. PFCL was used intra-operatively in 30 cases (PFCL group and X group). The eyes were implanted with SO (silicon oil subgroup), PFC (C3F8 sub group) and SF6 (SF6 sub-group) in twenty cases each. Apart from best corrected visual acuity (BCVA), the retinal status and the longevity of gas when used, changes and reaction in both the anterior and posterior segments were noted. RESULT: The difference of postoperative BCVA in the PFCL and non-PFCL groups was statistically significant with p < 0.001. In both the PFCL and non-PFCL groups the difference between preoperative and postoperative BCVA was statistically significant with p < 0.0001. All three vitreous substitutes studied are effective given the case where they had been utilised. CONCLUSION: PFCL is invaluable in the management of complicated retinal detachment (RD). Where a vitreous microsurgery is indicated, the visual outcome is good. SF6 is useful for short term tamponade. Silicon oil and C3F8 are useful for longer tamponade. PMID- 27375323 TI - 5-Fluoro-Uracil and Low Molecular Weight Heparin in the Management of Proliferative Vitreo-retinopathy. AB - BACKGROUND: Proliferative vitreo-retinopathy (PVR) is the most common cause of failed repair of a primary rhegmatogenous retinal detachment (RRD). The success rates for the surgery of complicated RRD has doubled with improved vitreous techniques from 35-40% to approximately 65-75% at six months. However, despite these advances, recurrent vitreo-retinal traction leads to re-detachment in more than one-fourths of the initially successful cases. The use of adjunctive treatments to prevent cellular proliferation holds promise for the prevention of PVR or recurrences after surgery. One focus has been on the use of intra-vitreal antimetabolites to prevent the occurrence of PVR. METHODS: Thirty patients of complicated retinal detachment associated with PVR, C1 or more were managed by vitreo-retinal (VR) surgery with the addition of 250 MUg / ml of 5-fluorouracil (5FU) and 1 IU / ml of low molecular weight heparin (LMWH) to the vitreous infusion. The patients were examined for any evidence of PVR till 180 days as also for any systemic or other ophthalmic complication. RESULT: Out of the 30 cases in the study group, 25 (83.34%) cases had retinal settlement at the end of six weeks, which is similar to the outcomes of conventional VR surgery. There was no case of any serious complication. CONCLUSION: The addition of LMWH and 5FU did not enhance the outcome of VR surgery. PMID- 27375322 TI - Comparative Study of Predeposit and Bedside Leucodepletion Filters. AB - BACKGROUND: Removal of leucocytes from cellular blood components is associated with reduction of several transfusion associated adverse reactions. METHODS: A total of 400 units of packed red blood cells (RBCs) were subjected to leucodepletion at room temperature and 4 degrees C using different commercially available prestorage and bedside filters (Terumo Penpol Immugard III and Pall Medical BPF-4). Pre-filtration and post-filtration parameters were compared to assess the efficacy of prestorage leucodepletion vis-a-vis bedside leucodepletion and the requirement of universal leucodepletion. RESULT: Mean post-filtration red cell recovery ranged from 88.49-93.49% with all bags showing more than 85% red cell recovery. Mean post-filtration residual leucocyte count ranged from 0.205 * 10(6)-0.338 * 10(6)/bag with all bags showing more than log 3 leucoreduction. Prestorage leucoreduction achieved by the polyurethane filter was better than that achieved by the polyester filter. Red cell recovery with the bedside filters at room temperature was significantly less than that with prestorage filters at either temperature. CONCLUSION: This study suggests that prestorage leucoreduction is preferable over bedside leucoreduction and that polyurethane filters are better than polyester filters since leucodepletion achieved with the former is higher. We recommend selective log 3 leucodepletion using polyurethane prestorage filters for patients with specific indications. PMID- 27375324 TI - Picture Quiz. PMID- 27375325 TI - Meconium Aspiration Syndrome: An Insight. AB - Meconium aspiration syndrome (MAS) is respiratory distress in a newborn baby caused by the presence of meconium in the tracheobronchial airways. The aspiration of meconium stained amniotic fluid by the fetus can happen during antepartum or intrapartum periods and can result in airway obstruction, interference with alveolar gas exchange, chemical pneumonitis as well as surfactant dysfunction. These pulmonary effects cause gross ventilation-perfusion mismatching. To complicate matters further, many infants with MAS have primary or secondary persistent pulmonary hypertension of the newborn as a result of chronic in utero stress and thickening of the pulmonary vessels. Although meconium is sterile, its presence in the air passages can predispose the infant to pulmonary infection. MAS is essentially a clinical diagnosis and should always be suspected in a child with respiratory distress and meconium-stained amniotic fluid at delivery. Though a known entity for a long time, its management still remains contentious. Intubation and direct tracheal suction is performed when meconium is observed in the amniotic fluid and the infant is not vigorous. Subsequent management involves ventilation, surfactant instillation and lavage, inhaled nitric oxide and high frequency ventilation. The role of steroids continues to be controversial. PMID- 27375326 TI - Radiotherapy: Basic Concepts and Recent Advances. AB - Radiation therapy (RT) is a clinical modality dealing with the use of ionizing radiations to treat malignant neoplasias (and occasionally benign diseases). Since its inception, the goal of RT has been to cure cancer locally without excessive side effects. The most important factors affecting the results of RT are the tumor type, its location and regional extent, the anatomic area of involvement and the geometric accuracy with which a calculated radiation dose is delivered. Although higher doses of radiation can produce better tumor control, the dosage which can be given is limited by the possibility of normal tissue damage. Approximately 60-65% of all cancer patients require RT as the sole treatment modality and / or in combination with surgery or chemotherapeutic drugs. There is a huge gap between demand and supply of radiotherapy facilities and infrastructure. Most of the oncocentres are located in urban areas in private sector and are beyond the reach of the common man. PMID- 27375327 TI - Use of Surgical Facemasks in the Operation Theatre: Effective or Habit? PMID- 27375328 TI - Antenatally Diagnosed Posterior Urethral Valves: A Dilemma. PMID- 27375329 TI - Radiological quiz. PMID- 27375330 TI - Prenatal Diagnosis of Gaucher Disease. PMID- 27375331 TI - An Unusual Case of Pain Abdomen. PMID- 27375332 TI - Stavudine Induced Acute Pancreatitis in Paediatric Human Immunodeficiency Virus Infection. PMID- 27375333 TI - Spontaneous Resolution of Corneal Oedema after Inadvertent Descemetorhexis during Cataract Surgery. PMID- 27375334 TI - Symptom Triggered Therapy in Delirium Tremens. PMID- 27375335 TI - Upshaw-Schulman Syndrome. PMID- 27375336 TI - Surgically Assisted Maxillo-mandibular Transverse Expansion. PMID- 27375337 TI - Filarial Dance in a Breast Lump. PMID- 27375338 TI - Migrating Extraluminal Foreign Body Hypopharynx. PMID- 27375339 TI - Severe Symptomatic Diuretic Induced Hyponatremia. PMID- 27375340 TI - First reported case of African Viper bite treated with Indian Polyvalent Anti Snake Venom. PMID- 27375341 TI - High transpiration efficiency increases pod yield under intermittent drought in dry and hot atmospheric conditions but less so under wetter and cooler conditions in groundnut (Arachis hypogaea (L.)). AB - Water limitation is a major yield limiting factor in groundnut and transpiration efficiency (TE) is considered the main target for improvement, but TE being difficult to measure it has mostly been screened with surrogates. The paper re explore the contribution of TE to grain yield in peanut by using a novel experimental approach in which TE is measured gravimetrically throughout the crop life cycle, in addition to measurement of TE surrogates. Experimentation was carried out with the groundnut reference collection (n = 288), across seasons varying for the evaporative demand (vapor pressure deficit, VPD) and across both fully irrigated and intermittent water stress conditions. There was large genotypic variation for TE under water stress in both low and high VPD season but the range was larger (5-fold) in the high- than in the low-VPD season (2-fold). Under water stress in both seasons, yield was closely related to the harvest index (HI) while TE related directly to yield only in the high VPD season. After discounting the direct HI effect on yield, TE explained a large portion of the remaining yield variations in both seasons, although marginally in the low VPD season. By contrast, the total water extracted from the soil profile, which varied between genotypes, did not relate directly to pod yield and neither to the yield residuals unexplained by HI. Surrogates for TE (specific leaf area, SLA, and SPAD chlorophyll meter readings, SCMR) never showed any significant correlation to TE measurements. Therefore, TE is an important factor explaining yield differences in groundnut under high VPD environments, suggesting that stomatal regulation under high VPD, rather than high photosynthetic rate as proposed earlier, may have a key role to play in the large TE differences found, which open new opportunities to breed improved groundnut for high VPD. PMID- 27375342 TI - Effect of the chamber wall on fluorocarbon-assisted atomic layer etching of SiO2 using cyclic Ar/C4F8 plasma. AB - The authors studied the effect of the temperature and chemical state of the chamber wall on process performance for atomic layer etching of SiO2 using a steady-state Ar plasma, periodic injection of a defined number of C4F8 molecules, and synchronized plasma-based Ar+ ion bombardment. To evaluate these effects, the authors measured the quartz coupling window temperature. The plasma gas phase chemistry was characterized using optical emission spectroscopy. It was found that although the thickness of the polymer film deposited in each cycle is constant, the etching behavior changed, which is likely related to a change in the plasma gas phase chemistry. The authors found that the main gas phase changes occur after C4F8 injection. The C4F8 and the quartz window react and generate SiF and CO. The emission intensity changes with wall surface state and temperature. Therefore, changes in the plasma gas species generation can lead to a shift in etching performance during processing. During initial cycles, minimal etching is observed, while etching gradually increases with cycle number. PMID- 27375343 TI - Ambient awareness: From random noise to digital closeness in online social networks. AB - Ambient awareness refers to the awareness social media users develop of their online network in result of being constantly exposed to social information, such as microblogging updates. Although each individual bit of information can seem like random noise, their incessant reception can amass to a coherent representation of social others. Despite its growing popularity and important implications for social media research, ambient awareness on public social media has not been studied empirically. We provide evidence for the occurrence of ambient awareness and examine key questions related to its content and functions. A diverse sample of participants reported experiencing awareness, both as a general feeling towards their network as a whole, and as knowledge of individual members of the network, whom they had not met in real life. Our results indicate that ambient awareness can develop peripherally, from fragmented information and in the relative absence of extensive one-to-one communication. We report the effects of demographics, media use, and network variables and discuss the implications of ambient awareness for relational and informational processes online. PMID- 27375345 TI - When and Where to Transfer for Bayes Net Parameter Learning. AB - Learning Bayesian networks from scarce data is a major challenge in real-world applications where data are hard to acquire. Transfer learning techniques attempt to address this by leveraging data from different but related problems. For example, it may be possible to exploit medical diagnosis data from a different country. A challenge with this approach is heterogeneous relatedness to the target, both within and across source networks. In this paper we introduce the Bayesian network parameter transfer learning (BNPTL) algorithm to reason about both network and fragment (sub-graph) relatedness. BNPTL addresses (i) how to find the most relevant source network and network fragments to transfer, and (ii) how to fuse source and target parameters in a robust way. In addition to improving target task performance, explicit reasoning allows us to diagnose network and fragment relatedness across BNs, even if latent variables are present, or if their state space is heterogeneous. This is important in some applications where relatedness itself is an output of interest. Experimental results demonstrate the superiority of BNPTL at various scarcities and source relevance levels compared to single task learning and other state-of-the-art parameter transfer methods. Moreover, we demonstrate successful application to real-world medical case studies. PMID- 27375344 TI - Dynamically adapted context-specific hyper-articulation: Feedback from interlocutors affects speakers' subsequent pronunciations. AB - We ask whether speakers can adapt their productions when feedback from their interlocutors suggests that previous productions were perceptually confusable. To address this question, we use a novel web-based task-oriented paradigm for speech recording, in which participants produce instructions towards a (simulated) partner with naturalistic response times. We manipulate (1) whether a target word with a voiceless plosive (e.g., pill) occurs in the presence of a voiced competitor (bill) or an unrelated word (food) and (2) whether or not the simulated partner occasionally misunderstands the target word. Speakers hyper articulated the target word when a voiced competitor was present. Moreover, the size of the hyper-articulation effect was nearly doubled when partners occasionally misunderstood the instruction. A novel type of distributional analysis further suggests that hyper-articulation did not change the target of production, but rather reduced the probability of perceptually ambiguous or confusable productions. These results were obtained in the absence of explicit clarification requests, and persisted across words and over trials. Our findings suggest that speakers adapt their pronunciations based on the perceived communicative success of their previous productions in the current environment. We discuss why speakers make adaptive changes to their speech and what mechanisms might underlie speakers' ability to do so. PMID- 27375346 TI - Perceived Parenting and Adolescent Cyber-Bullying: Examining the Intervening Role of Autonomy and Relatedness Need Satisfaction, Empathic Concern and Recognition of Humanness. AB - Due to the progress in information technology, cyber-bullying is becoming one of the most common forms of interpersonal harm, especially among teenagers. The present study (N = 548) aimed to investigate the relation between perceived parenting style (in terms of autonomy support and psychological control) and cyber-bullying in adolescence. Thereby, the study tested for the intervening role of adolescent need satisfaction (i.e., autonomy and relatedness), empathic concern towards others, and adolescents' recognition of full humanness to cyber bullying offenders and victims. Findings revealed both a direct and an indirect relation between parenting and cyber-bullying. More specifically, parental psychological control directly predicted cyber-bullying, whereas parental autonomy support related to less cyber-bullying indirectly, as it was associated with the satisfaction of adolescents' need for autonomy, which predicted more empathic concern towards others, which in turn differentially related to recognition of humanness to victims and bullies. The discussion focuses on the implications of the current findings. PMID- 27375347 TI - Group-Schematherapy for Adolescents: Results from a Naturalistic Multiple Case Study. AB - Personality disorders are complex mental health problems, associated with chronic dysfunction in several life domains. Adolescents suffer from these disorders as well. The present study is a naturalistic case study, investigating whether group schematherapy (GST) can be applied to adolescents with personality disorders or personality disorder traits. Four clinically referred patients were included and completed questionnaires on quality of life, symptoms of psychopathology, schema modes, early maladaptive schemas, and schema coping styles. Patients participated in weekly GST sessions complemented by weekly or 2-weekly individual sessions. The parents of the adolescents participated in a separate parent group. From pre- to post-treatment, results demonstrated improvements for some patients in quality of life and symptoms of psychopathology. Changes in a number of modes and schemas were observed in all patients from pre- to post-therapy. In addition to assessing changes from pre- to post-treatment, the current study investigated the temporal changes in modes during therapy as well. Results demonstrated that maladaptive modes decreased, whereas healthy modes increased for all patients across the course of therapy. The present study provides preliminary support for the applicability of GST for adolescents as well as the effectiveness of GST. It is a starting point for further research on this intervention. PMID- 27375348 TI - Expressive visual text-to-speech as an assistive technology for individuals with autism spectrum conditions. AB - Adults with Autism Spectrum Conditions (ASC) experience marked difficulties in recognising the emotions of others and responding appropriately. The clinical characteristics of ASC mean that face to face or group interventions may not be appropriate for this clinical group. This article explores the potential of a new interactive technology, converting text to emotionally expressive speech, to improve emotion processing ability and attention to faces in adults with ASC. We demonstrate a method for generating a near-videorealistic avatar (XpressiveTalk), which can produce a video of a face uttering inputted text, in a large variety of emotional tones. We then demonstrate that general population adults can correctly recognize the emotions portrayed by XpressiveTalk. Adults with ASC are significantly less accurate than controls, but still above chance levels for inferring emotions from XpressiveTalk. Both groups are significantly more accurate when inferring sad emotions from XpressiveTalk compared to the original actress, and rate these expressions as significantly more preferred and realistic. The potential applications for XpressiveTalk as an assistive technology for adults with ASC is discussed. PMID- 27375349 TI - It's Back to School Time!: The Role of School Nurses in Preparing a Medically Safe and Supportive Environment for Students with Diabetes. PMID- 27375350 TI - TRACTABLE DIFFUSION AND COALESCENT PROCESSES FOR WEAKLY CORRELATED LOCI. AB - Widely used models in genetics include the Wright-Fisher diffusion and its moment dual, Kingman's coalescent. Each has a multilocus extension but under neither extension is the sampling distribution available in closed-form, and their computation is extremely difficult. In this paper we derive two new multilocus population genetic models, one a diffusion and the other a coalescent process, which are much simpler than the standard models, but which capture their key properties for large recombination rates. The diffusion model is based on a central limit theorem for density dependent population processes, and we show that the sampling distribution is a linear combination of moments of Gaussian distributions and hence available in closed-form. The coalescent process is based on a probabilistic coupling of the ancestral recombination graph to a simpler genealogical process which exposes the leading dynamics of the former. We further demonstrate that when we consider the sampling distribution as an asymptotic expansion in inverse powers of the recombination parameter, the sampling distributions of the new models agree with the standard ones up to the first two orders. PMID- 27375351 TI - Targeted next-generation sequencing extends the phenotypic and mutational spectrums for EYS mutations. AB - PURPOSE: We aim to determine genetic lesions with a phenotypic correlation in four Chinese families with autosomal recessive retinitis pigmentosa (RP). METHODS: Medical histories were carefully reviewed. All patients received comprehensive ophthalmic evaluations. The next-generation sequencing (NGS) approach targeting a panel of 205 retinal disease-relevant genes and 15 candidate genes was selectively performed on probands from the four recruited families for mutation detection. Online predictive software and crystal structure modeling were also applied to test the potential pathogenic effects of identified mutations. RESULTS: Of the four families, two were diagnosed with RP sino pigmento (RPSP). Patients with RPSP claimed to have earlier RP age of onset but slower disease progression. Five mutations in the eyes shut homolog (EYS) gene, involving two novel (c.7228+1G>A and c.9248G>A) and three recurrent mutations (c.4957dupA, c.6416G>A and c.6557G>A), were found as RP causative in the four families. The missense variant c.5093T>C was determined to be a variant of unknown significance (VUS) due to the variant's colocalization in the same allele with the reported pathogenic mutation c.6416G>A. The two novel variants were further confirmed absent in 100 unrelated healthy controls. Online predictive software indicated potential pathogenicity of the three missense mutations. Further, crystal structural modeling suggested generation of two abnormal hydrogen bonds by the missense mutation p.G2186E (c.6557G>A) and elongation of its neighboring beta-sheet induced by p.G3083D (c.9248G>A), which could alter the tertiary structure of the eys protein and thus interrupt its physicochemical properties. CONCLUSIONS: Taken together, with the targeted NGS approach, we reveal novel EYS mutations and prove the efficiency of targeted NGS in the genetic diagnoses of RP. We also first report the correlation between EYS mutations and RPSP. The genotypic-phenotypic relationship in all Chinese patients carrying mutations in the EYS gene were also reviewed and summarized. PMID- 27375354 TI - Elucidation of Softening Mechanism in Rinse-Cycle Fabric Softeners. Part 2: Uneven Adsorption-The Key Phenomenon to the Effect of Fabric Softeners. AB - We investigated the actual factor determining the softening effect of a fabric softener. The adsorption area of the softener on model cotton cloths and yarns was identified using bromophenol blue. There was almost no softener at the cross points of the yarns in the cloth samples or in the inner part of the yarns. The softening performance was better when there was less softener at the cross-points of the yarns than when the yarns were evenly covered by the softener. Thus we conclude that the presence of softener at the cross-points of yarns is not a vital factor in the softening effect. In addition, more softener was found on the outer part of the yarn than the inner part, indicating gradation in the adsorption pattern of the softener. Thus, we propose that more softener is adsorbed on the exposed part of the yarn in a cloth, and the formation of a hydrogen-bonding network containing bound water is inhibited, thus softening the outer part of the yarn. However, the presence of a small amount of softener in the inner part of the yarn preserves the hydrogen-bonding network. Favorable elasticity, or bounce, of the yarns and cloth is realized when an appropriate amount of softener is used. Excess softener would reach the inner part of the yarn, reducing the diameter of the core part of the yarn, making the cloth appear wilted. PMID- 27375353 TI - Quantitative modeling of the molecular steps underlying shut-off of rhodopsin activity in rod phototransduction. AB - PURPOSE: To examine the predictions of alternative models for the stochastic shut off of activated rhodopsin (R*) and their implications for the interpretation of experimentally recorded single-photon responses (SPRs) in mammalian rods. THEORY: We analyze the transitions that an activated R* molecule undergoes as a result of successive phosphorylation steps and arrestin binding. We consider certain simplifying cases for the relative magnitudes of the reaction rate constants and derive the probability distributions for the time to arrestin binding. In addition to the conventional model in which R* catalytic activity declines in a graded manner with successive phosphorylations, we analyze two cases in which the activity is assumed to occur not via multiple small steps upon each phosphorylation but via a single large step. We refer to these latter two cases as the binary R* shut-off and three-state R* shut-off models. METHODS: We simulate R*'s stochastic reactions numerically for the three models. In the simplifying cases for the ratio of rate constants in the binary and three-state models, we show that the probability distribution of the time to arrestin binding is accurately predicted. To simulate SPRs, we then integrate the differential equations for the downstream reactions using a standard model of the rod outer segment that includes longitudinal diffusion of cGMP and Ca(2+). RESULTS: Our simulations of SPRs in the conventional model of graded shut-off of R* conform closely to the simulations in a recent study. However, the gain factor required to account for the observed mean SPR amplitude is higher than can be accounted for from biochemical experiments. In addition, a substantial minority of the simulated SPRs exhibit features that have not been reported in published experiments. Our simulations of SPRs using the model of binary R* shut-off appear to conform closely to experimental results for wild type (WT) mouse rods, and the required gain factor conforms to biochemical expectations. However, for the arrestin knockout (Arr(-/-)) phenotype, the predictions deviated from experimental findings and led us to invoke a low-activity state that R* enters before arrestin binding. Our simulations of this three-state R* shut-off model are very similar to those of the binary model in the WT case but are preferred because they appear to accurately predict the mean SPRs for four mutant phenotypes, Arr(+/-), Arr(-/-), GRK1(+/-), and GRK1(-/-), in addition to the WT phenotype. When we additionally treated the formation and shut-off of activated phosphodiesterase (E*) as stochastic, the simulated SPRs appeared even more similar to real SPRs, and there was very little change in the ensemble mean and standard deviation or in the amplitude distribution. CONCLUSIONS: We conclude that the conventional model of graded reduction in R* activity through successive phosphorylation steps appears to be inconsistent with experimental results. Instead, we find that two variants of a model in which R* activity initially remains high and then declines abruptly after several phosphorylation steps appears capable of providing a better description of experimentally measured SPRs. PMID- 27375352 TI - Expression pattern in retinal photoreceptors of POMGnT1, a protein involved in muscle-eye-brain disease. AB - PURPOSE: The POMGNT1 gene, encoding protein O-linked-mannose beta-1,2-N acetylglucosaminyltransferase 1, is associated with muscle-eye-brain disease (MEB) and other dystroglycanopathies. This gene's lack of function or expression causes hypoglycosylation of alpha-dystroglycan (alpha-DG) in the muscle and the central nervous system, including the brain and the retina. The ocular symptoms of patients with MEB include retinal degeneration and detachment, glaucoma, and abnormal electroretinogram. Nevertheless, the POMGnT1 expression pattern in the healthy mammalian retina has not yet been investigated. In this work, we address the expression of the POMGNT1 gene in the healthy retina of a variety of mammals and characterize the distribution pattern of this gene in the adult mouse retina and the 661W photoreceptor cell line. METHODS: Using reverse transcription (RT) PCR and immunoblotting, we studied POMGNT1 expression at the mRNA and protein levels in various mammalian species, from rodents to humans. Immunofluorescence confocal microscopy analyses were performed to characterize the distribution profile of its protein product in mouse retinal sections and in 661W cultured cells. The intranuclear distribution of POMT1 and POMT2, the two enzymes preceding POMGnT1 in the alpha-DG O-mannosyl glycosylation pathway, was also analyzed. RESULTS: POMGNT1 mRNA and its encoded protein were expressed in the neural retina of all mammals studied. POMGnT1 was located in the cytoplasmic fraction in the mouse retina and concentrated in the myoid portion of the photoreceptor inner segments, where the protein colocalized with GM130, a Golgi complex marker. The presence of POMGnT1 in the Golgi complex was also evident in 661W cells. However, and in contrast to retinal tissue, POMGnT1 additionally accumulated in the nucleus of the 661W photoreceptors. Colocalization was found within this organelle between POMGnT1 and POMT1/2, the latter associated with euchromatic regions of the nucleus. CONCLUSIONS: Our results indicate that POMGnT1 participates not only in the synthesis of O-mannosyl glycans added to alpha-DG in the Golgi complex but also in the glycosylation of other yet-to-be identified proteins in the nucleus of mouse photoreceptors. PMID- 27375356 TI - Twenty-Five New Viruses Associated with the Drosophilidae (Diptera). AB - Drosophila melanogaster is an important laboratory model for studies of antiviral immunity in invertebrates, and Drosophila species provide a valuable system to study virus host range and host switching. Here, we use metagenomic RNA sequencing of about 1600 adult flies to discover 25 new RNA viruses associated with six different drosophilid hosts in the wild. We also provide a comprehensive listing of viruses previously reported from the Drosophilidae. The new viruses include Iflaviruses, Rhabdoviruses, Nodaviruses, and Reoviruses, and members of unclassified lineages distantly related to Negeviruses, Sobemoviruses, Poleroviruses, Flaviviridae, and Tombusviridae. Among these are close relatives of Drosophila X virus and Flock House virus, which we find in association with wild Drosophila immigrans. These two viruses are widely used in experimental studies but have not been previously reported to naturally infect Drosophila. Although we detect no new DNA viruses, in D. immigrans and Drosophila obscura, we identify sequences very closely related to Armadillidium vulgare iridescent virus (Invertebrate iridescent virus 31), bringing the total number of DNA viruses found in the Drosophilidae to three. PMID- 27375357 TI - Rural, Pregnant, and Opioid Dependent: A Systematic Review. AB - The nature, impact, and treatment of substance use during pregnancy are well described for women living in urban settings. Less is known about pregnant substance-using women living in rural communities. The objective of this review is to describe the existing evidence for the management of substance use in pregnant women living in rural areas. A systematic review of the literature was conducted using PubMed, Embase, and the Cochrane Database of Systematic Reviews, and the quality of the evidence was assessed using the GRADE system. Twenty-two articles that met the inclusion criteria were identified. Descriptive studies document high rates of smoking, marijuana, and polysubstance use among rural, substance-using pregnant women compared to their urban counterparts. Management of substance use disorders is limited by access to and acceptability of treatment modalities. Several innovative, integrated addiction and prenatal care programs have been developed, which may serve as models for management of substance use during pregnancy in rural settings. PMID- 27375355 TI - Freshwater Metaviromics and Bacteriophages: A Current Assessment of the State of the Art in Relation to Bioinformatic Challenges. AB - Advances in bioinformatics and sequencing technologies have allowed for the analysis of complex microbial communities at an unprecedented rate. While much focus is often placed on the cellular members of these communities, viruses play a pivotal role, particularly bacteria-infecting viruses (bacteriophages); phages mediate global biogeochemical processes and drive microbial evolution through bacterial grazing and horizontal gene transfer. Despite their importance and ubiquity in nature, very little is known about the diversity and structure of viral communities. Though the need for culture-based methods for viral identification has been somewhat circumvented through metagenomic techniques, the analysis of metaviromic data is marred with many unique issues. In this review, we examine the current bioinformatic approaches for metavirome analyses and the inherent challenges facing the field as illustrated by the ongoing efforts in the exploration of freshwater phage populations. PMID- 27375358 TI - Mining Health-Related Issues in Consumer Product Reviews by Using Scalable Text Analytics. AB - In an era when most of our life activities are digitized and recorded, opportunities abound to gain insights about population health. Online product reviews present a unique data source that is currently underexplored. Health related information, although scarce, can be systematically mined in online product reviews. Leveraging natural language processing and machine learning tools, we were able to mine 1.3 million grocery product reviews for health related information. The objectives of the study were as follows: (1) conduct quantitative and qualitative analysis on the types of health issues found in consumer product reviews; (2) develop a machine learning classifier to detect reviews that contain health-related issues; and (3) gain insights about the task characteristics and challenges for text analytics to guide future research. PMID- 27375359 TI - Effect of Trapping Methods, Weather, and Landscape on Estimates of the Culex Vector Mosquito Abundance. AB - The local abundance of Culex mosquitoes is a central factor adding to the risk of West Nile virus transmission, and vector abundance data influence public health decisions. This study evaluated differences in abundance estimates from mosquitoes trapped using two common methods: CO2-baited CDC light traps and infusion-baited gravid traps in suburban, Chicago, Illinois. On a weekly basis, the two methods were modestly correlated (r = 0.219) across 71 weeks over 4 years. Lagged weather conditions of up to four weeks were associated with the number of mosquitoes collected in light and gravid traps. Collections in light traps were higher with higher temperature in the same week, higher precipitation one, two, and four weeks before the week of trapping, and lower maximum average wind speed. Collections in gravid traps were higher with higher temperature in the same week and one week earlier, lower temperature four weeks earlier, and with higher precipitation two and four weeks earlier. Culex abundance estimates from light traps were significantly higher in semi-natural areas compared to residential areas, but abundance estimates from gravid traps did not vary by the landscape type. These results highlight the importance of the surveillance methods used in the assessment of local Culex abundance estimates. Measures of risk of exposure to West Nile virus should assess carefully how mosquito abundance has been estimated and integrated into assessments of transmission risk. PMID- 27375360 TI - Liposomal-encapsulated Ascorbic Acid: Influence on Vitamin C Bioavailability and Capacity to Protect Against Ischemia-Reperfusion Injury. AB - Intravenous administration of vitamin C has been shown to decrease oxidative stress and, in some instances, improve physiological function in adult humans. Oral vitamin C administration is typically less effective than intravenous, due in part to inferior vitamin C bioavailability. The purpose of this study was to determine the efficacy of oral delivery of vitamin C encapsulated in liposomes. On 4 separate randomly ordered occasions, 11 men and women were administered an oral placebo, or 4 g of vitamin C via oral, oral liposomal, or intravenous delivery. The data indicate that oral delivery of 4 g of vitamin C encapsulated in liposomes (1) produces circulating concentrations of vitamin C that are greater than unencapsulated oral but less than intravenous administration and (2) provides protection from ischemia-reperfusion-mediated oxidative stress that is similar to the protection provided by unencapsulated oral and intravenous administrations. PMID- 27375361 TI - Chronic Myeloid Leukemia in Nigerian Patients: Anemia is an Independent Predictor of Overall Survival. AB - OBJECTIVES: The advent of the tyrosine kinase inhibitors has markedly changed the prognostic outlook for patients with Ph(+) and/or BCR-ABL1 (+) chronic myeloid leukemia (CML). This study was designed to assess the overall survival (OS) of Nigerian patients with CML receiving imatinib therapy and to identify the significant predictors of OS. METHODS: All patients with CML receiving imatinib from July 2003 to June 2013 were studied. The clinical and hematological parameters were studied. The Kaplan-Meier technique was used to estimate the OS and median survival. P-value of <0.05 was considered as statistically significant. RESULTS: The median age of all 527 patients (male/female = 320/207) was 37 (range 10-87) years. There were 472, 47, and 7 in chronic phase (CP), accelerated phase, and blastic phase, respectively. As at June 2013, 442 patients are alive. The median survival was 105.7 months (95% confidence interval [CI], 91.5-119.9); while OS at one, two, and five years were 95%, 90%, and 75%, respectively. Multivariate Cox regression analysis revealed that OS was significantly better in patients diagnosed with CP (P = 0.001, odds ratio = 1.576, 95% CI = 1.205-2.061) or not in patients with anemia (P = 0.031, odds ratio = 1.666, 95% CI = 1.047-2.649). Combining these variables yielded three prognostic groups: CP without anemia, CP with anemia, and non-CP, with significantly different median OS of 123.3, 92.0, and 74.7 months, respectively (chi (2) = 22.042, P = 0.000016). CONCLUSION: This study has clearly shown that for Nigerian patients with CML, the clinical phase of the disease at diagnosis and the hematocrit can be used to stratify patients into low, intermediate, and high risk groups. PMID- 27375362 TI - Comparing the Roles of EUS, ERCP and MRCP in Idiopathic Acute Recurrent Pancreatitis. AB - Acute recurrent pancreatitis (ARP) is defined as more than two attacks of acute pancreatitis with complete or almost complete resolution of symptoms and signs of pancreatitis between episodes. The initial evaluation fails to detect the cause of ARP in 10%-30% of patients, whose condition is classified as idiopathic ARP. Endoscopic ultrasound (EUS) has gained increasing attention as a useful imaging modality for the pancreas and the extrahepatic biliary tree. The close proximity of the pancreas to the digestive tract allows EUS to obtain detailed images of this organ. This review aims to record pancreaticobiliary endoscopic ultrasound (EUS) and other imaging modalities in the clinical management of patients with idiopathic ARP. PMID- 27375363 TI - Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases. AB - Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and brain tumors. PMID- 27375364 TI - Idelalisib therapy of indolent B-cell malignancies: chronic lymphocytic leukemia and small lymphocytic or follicular lymphomas. AB - Chronic lymphocytic leukemia, small lymphocytic lymphoma, and follicular lymphoma are indolent B-cell lymphoproliferative disorders that mainly affect an older population. Although the majority of patients in need of treatment derive significant benefit from conventional chemotherapeutic agents as well as monoclonal antibodies, less toxic and more effective treatments are needed. Novel agents that inhibit the B-cell receptor signaling pathway have shown promising outcomes in these disorders. Idelalisib is a potent selective oral inhibitor of phosphatidylinositol 3-kinase delta and has shown significant clinical activity in B-cell malignancies. In this review, we summarize the clinical trial data using idelalisib as monotherapy or in combination with rituximab for the treatment of relapsed/refractory disease. The adverse effect profile includes autoimmune disorders such as transaminitis, colitis, and pneumonitis. Given the efficacy and manageable toxicity profile of idelalisib, it is being increasingly incorporated into the management of indolent B-cell malignancies. PMID- 27375366 TI - Design and analysis of UW-OFDM signals. AB - Unique word-orthogonal frequency division multiplexing (UW-OFDM) is a novel signaling concept where the guard interval is implemented as a deterministic sequence, the so-called unique word. The UW is generated by introducing a certain level of redundancy in the frequency domain. Different data estimation strategies and the favourable bit error ratio (BER) performance of UW-OFDM, as well as comparisons to competing concepts have already extensively been discussed in previous papers. This work focuses on the different possibilities on how to generate UW-OFDM signals. The optimality of the two-step over the direct approach in systematic UW-OFDM is proved analytically, we present a heuristic algorithm that allows a fast numerical optimization of the redundant subcarrier positions, and we show that our original intuitive approach of spreading the redundant subcarriers in systematically encoded UW-OFDM by minimizing the mean redundant energy is practically also optimum w.r.t. transceiver based cost functions. Finally, we derive closed form approximations of the statistical symbol distributions on individual subcarriers as well as the redundant energy distribution and compare them with numerically found results. PMID- 27375365 TI - How reliably can a material be classified as a nanomaterial? Available particle sizing techniques at work. AB - ABSTRACT: Currently established and projected regulatory frameworks require the classification of materials (whether nano or non-nano) as specified by respective definitions, most of which are based on the size of the constituent particles. This brings up the question if currently available techniques for particle size determination are capable of reliably classifying materials that potentially fall under these definitions. In this study, a wide variety of characterisation techniques, including counting, fractionating, and spectroscopic techniques, has been applied to the same set of materials under harmonised conditions. The selected materials comprised well-defined quality control materials (spherical, monodisperse) as well as industrial materials of complex shapes and considerable polydispersity. As a result, each technique could be evaluated with respect to the determination of the number-weighted median size. Recommendations on the most appropriate and efficient use of techniques for different types of material are given. GRAPHICAL ABSTRACT: PMID- 27375367 TI - The chemical, mechanical, and physical properties of 3D printed materials composed of TiO2-ABS nanocomposites. AB - To expand the chemical capabilities of 3D printed structures generated from commercial thermoplastic printers, we have produced and printed polymer filaments that contain inorganic nanoparticles. TiO2 was dispersed into acrylonitrile butadiene styrene (ABS) and extruded into filaments with 1.75 mm diameters. We produced filaments with TiO2 compositions of 1%, 5%, and 10% (kg/kg) and printed structures using a commercial 3D printer. Our experiments suggest that ABS undergoes minor degradation in the presence of TiO2 during the different processing steps. The measured mechanical properties (strain and Young's modulus) for all of the composites are similar to those of structures printed from the pure polymer. TiO2 incorporation at 1% negatively affects the stress at breaking point and the flexural stress. Structures produced from the 5 and 10% nanocomposites display a higher breaking point stress than those printed from the pure polymer. TiO2 within the printed matrix was able to quench the intrinsic fluorescence of the polymer. TiO2 was also able to photocatalyze the degradation of a rhodamine 6G in solution. These experiments display chemical reactivity in nanocomposites that are printed using commercial 3D printers, and we expect that our methodology will help to inform others who seek to incorporate catalytic nanoparticles in 3D printed structures. PMID- 27375368 TI - PARG deficiency is neither synthetic lethal with BRCA1 nor PTEN deficiency. AB - BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors have entered the clinics for their promising anticancer effect as adjuvant in chemo- and radiotherapy and as single agent on BRCA-mutated tumours. Poly(ADP-ribose) glycohydrolase (PARG) deficiency was also shown to potentiate the cytotoxicity of genotoxic agents and irradiation. The aim of this study is to investigate the effect of PARG deficiency on BRCA1- and/or PTEN-deficient tumour cells. METHODS: Since no PARG inhibitors are available for in vivo studies, PARG was depleted by siRNA in several cancer cell lines, proficient or deficient for BRCA1 and/or PTEN. The impact on cell survival was evaluated by colony formation assay and short-term viability assays. The effect of simultaneous PARG and BRCA1 depletion on homologous recombination (HR) efficacy was evaluated by immunodetection of RAD51 foci and using an in vivo HR assay. RESULTS: The BRCA1-deficient cell lines MDA-MB-436, HCC1937 and UWB1.289 showed mild sensitivity to PARG depletion, whereas no sensitivity was observed for the BRCA1-proficient MDA-MB-231, MDA-MB 468, MCF10A and U2OS cell lines. However, the BRCA1-reconstituted UWB1.289 cell lines was similarly sensitive to PARG depletion than the BRCA1-deficient UWB1.289, and the simultaneous depletion of PARG and BRCA1 and/or PTEN in MDA-MB 231 or U2OS cells was not more cytotoxic than depletion of BRCA1 or PTEN only. CONCLUSIONS: Some tumour cells displayed slight sensitivity to PARG deficiency, but this sensitivity could not be correlated to BRCA1- or PTEN-deficiency. Therefore, PARG depletion cannot be considered as a strategy to kill tumours cells mutated in BRCA1 or PTEN. PMID- 27375369 TI - CVXPY: A Python-Embedded Modeling Language for Convex Optimization. AB - CVXPY is a domain-specific language for convex optimization embedded in Python. It allows the user to express convex optimization problems in a natural syntax that follows the math, rather than in the restrictive standard form required by solvers. CVXPY makes it easy to combine convex optimization with high-level features of Python such as parallelism and object-oriented design. CVXPY is available at http://www.cvxpy.org/ under the GPL license, along with documentation and examples. PMID- 27375371 TI - Epidemiology of Locomotive Organ Disorders and Symptoms: An Estimation Using the Population-Based Cohorts in Japan. AB - Although locomotive organ diseases such as osteoporotic fractures and osteoarthritis are major reasons for disability and require support, little information is available regarding the epidemiology of musculoskeletal dysfunction and its symptoms including knee pain and lumbar pain in Japan. The research on osteoarthritis/osteoporosis against disability (ROAD) study is a prospective cohort study that aims at elucidating the environmental and genetic background for locomotive organ diseases, and has been ongoing since 2005. In this review, epidemiological indices such as prevalence of locomotive organ diseases including knee osteoarthritis, lumbar spondylosis, and osteoporosis were clarified using baseline survey results of the ROAD study. The number of subjects with such diseases was estimated. In addition, 3-year follow-up data from the ROAD study revealed the effect of osteoarthritis on the occurrence of osteoporosis, and vice versa. The prevalences of osteoarthritis and osteoporosis were shown to be high. Also, the large estimates of patients with these conditions suggest that urgent strategies are needed for addressing locomotive organ diseases that cause disability in the elderly. We also clarified the prevalence of knee pain, lumbar pain, and their co-existence using the survey results of the longitudinal cohorts of motor system organ study. We found that both knee pain and lumbar pain were prevalent in 12.2 % of the total population and the presence of knee pain affected lumbar pain, and vice versa. PMID- 27375370 TI - Locomotive Syndrome: Definition and Management. AB - Locomotive syndrome is a condition of reduced mobility due to impairment of locomotive organs. Since upright bipedal walking involves minutely controlled movement patterns, impairment of any aspect of the locomotive organs has the potential to adversely affect it. In addition to trauma, chronic diseases of the locomotive organs, which progress with repeated bouts of acute exacerbations, are common causes of the locomotive syndrome. In Japan's super-aging society, many people are likely to experience locomotive syndrome in the later part of their lives. Exercise intervention is effective in improving motor function, but because the subjects are elderly people with significant degenerative diseases of the locomotor organs, caution should be taken in choosing the type and intensity of exercise. The present review discusses the definition, current burden, diagnosis and interventions pertaining to the locomotive syndrome. The concept and measures are spreading throughout Japan as one of the national health policy targets. PMID- 27375372 TI - Locomotive Syndrome: Operational Definition Based on a Questionnaire, and Exercise Interventions on Mobility Dysfunction in Elderly People. AB - The increasing elderly population has a great impact on public health, and it is important to understand the progression of musculoskeletal disorders seen in this population. To establish useful preventative methods for such locomotive disorders, we must detect early changes in these individuals and identify those at risk in order to implement early interventions. The purpose of this review was: (1) to introduce an operational definition of locomotion dysfunction to prevent a care-need condition, and to verify its validity through a prospective cohort study, and (2) to review the indication of exercise intervention for multiple musculoskeletal involvements from the preceding literature. We developed a measurement scale called the Geriatric Locomotive Function Scale (GLFS)-25, which clearly reflects the degree of functional deterioration. We used it in a prospective cohort study of 314 patients recruited from 5 clinics or nursing care facilities and investigated the relationship of the GLFS-25 with 46 variables covering various clinical manifestations. The results clearly revealed that the change in the GLFS-25 classification reflected a common pattern seen in those with locomotive dysfunction. Recently, several important movements regarding physical activity and its public promotion have been advocated by international health organizations and journal publishers. Though it has not been confirmed yet that complex musculoskeletal diseases can be treated using therapeutic exercise, the promotion of physical activity appears promising. The degree of activity limitation in aged individuals with locomotive disorders can be evaluated using this scale, which may be useful in predicting the effectiveness of future interventions. PMID- 27375373 TI - The relationship between early maladaptive schemas and eating-disorder symptomatology among individuals seeking treatment for substance dependence. AB - Numerous studies have examined early maladaptive schemas (EMS) and their relationship to psychological disorders, including eating disorders (EDs) and substance use disorders (SUDs). However, to date, there are no empirical investigations that have examined the relationship between EMS and EDs among individuals seeking treatment for substance use. In an attempt to further elucidate this relationship, the purpose of the current, exploratory study was to examine the relationship between EMS, ED symptomatology (i.e., bulimia and binge eating but not anorexia), and substance use and to directly compare EMS among individuals with and without a probable ED diagnosis. Participants were 387 men and 132 women seeking residential treatment for substance use. Results demonstrated that 11 of the 18 EMS were significantly associated with ED. Moreover, patients with a probable ED scored significantly higher than patients without a probable ED on 8 of the 18 EMS. Results suggest that EMS are prevalent among individuals with ED pathology seeking treatment for substance use. Thus treatment programs could potentially benefit from the assessment and treatment of EMS among dually-diagnosed patients. Given the exploratory and preliminary nature of the study, continued research is needed to further examine the relationship between EMS, EDs, and substance use. PMID- 27375375 TI - Combined transversus abdominis plane block and rectus sheath block in laparoscopic peritoneal dialysis catheter insertion. PMID- 27375374 TI - Chitosan-Alginate Microcapsules Provide Gastric Protection and Intestinal Release of ICAM-1-Targeting Nanocarriers, Enabling GI Targeting In Vivo. AB - When administered intravenously, active targeting of drug nanocarriers (NCs) improves biodistribution and endocytosis. Targeting may also improve oral delivery of NCs to treat gastrointestinal (GI) pathologies or for systemic absoption. However, GI instability of targeting moieties compromises this strategy. We explored whether encapsulation of antibody-coated NCs in microcapsules would protect against gastric degradation, providing NCs release and targeting in intestinal conditions. We used nanoparticles coated with antibodies against intercellular adhesion molecule-1 (anti-ICAM) or non-specific IgG. NCs (~160-nm) were encapsulated in ~180-MUm microcapsules with an alginate core, in the absence or presence of a chitosan shell. We found >95% NC encapsulation within microcapsules and <10% NC release from microcapsules in storage. There was minimal NC release at gastric pH (<10%) and burst release at intestinal pH (75-85%), slightly attenuated by chitosan. Encapsulated NCs afforded increased protection against degradation (3-4 fold) and increased cell targeting (8-20 fold) after release vs. non-encapsulated NCs. Mouse oral gavage showed that microencapsulation provided 38-65% greater protection of anti-ICAM NCs in the GI tract, 40% lower gastric retention, and 4-9-fold enhanced intestinal biodistribution vs. non-encapsulated NCs. Therefore, microencapsulation of antibody-targeted NCs may enable active targeting strategies to be effective in the context of oral drug delivery. PMID- 27375376 TI - An infant's airway: A difficult terrain. PMID- 27375377 TI - Depth of insertion of right internal jugular central venous catheter: Comparison of topographic and formula methods. AB - BACKGROUND: Central venous catheters (CVCs) are inserted in many critically ill patients, but there is no gold standard in estimating their approximate depth of insertion. Many techniques have been described in literature. In this study, we compare the topographic method with the standard formula technique. MATERIALS AND METHODS: 260 patients, in whom central venous catheterization was warranted, were randomly assigned to either topographic method or formula method (130 in each group). The position of the CVC tip in relation to carina was measured on a postprocedure chest X-ray. The primary endpoint was the need for catheter repositioning. RESULTS: The majority of the CVCs tips positioned by the formula method were situated below the carina, and 68% of these catheters required repositioning after obtaining postprocedure chest X-ray (P < 0.001). CONCLUSION: The topographic method is superior to formula approach in estimating the depth of insertion of right internal jugular CVCs. PMID- 27375378 TI - To determine block establishment time of supraclavicular brachial plexus block using blunt versus short bevel needle: A prospective randomized trial. AB - BACKGROUND: Unintentional intraneural injection under ultrasound guidance (USG) with fine caliber needles and lower success rate with large caliber Tuohy needles in supraclavicular brachial plexus block (SCB) have been reported. MATERIALS AND METHODS: We undertook study to standardize the use of 20-gauge short versus blunt bevel needle for SCB. After approval of Institutional Ethics Committee and written informed consent, patients were randomized using computer-generated random number table to either of the two groups; blunt bevel needle group (n = 30): SCB under USG using 20-gauge Tuohy needle or short bevel needle group (n = 30): SCB under USG using 20-gauge short bevel needle. The primary outcome of the study was time to establishment of sensory and motor block of individual nerves, and secondary outcome was tolerability and any adverse effects. RESULTS: The time to establishment of sensory and motor block in individual nerve territory was similar in both the groups. The complete sensory and motor anesthesia was achieved in 78.3% patients and complete sensory and motor anesthesia after supplementary block was achieved in 86.6% patients. Paresthesias during SCB were recorded in 15 patients. Out of these eight patients were of blunt bevel group and seven patients were of short bevel group. None of the patients experienced any neurological adverse effects. CONCLUSION: The establishment of sensory and motor blockade of individual nerves was similar to 20-gauge short and blunt bevel needle under ultrasound guide with no neurological adverse events. PMID- 27375379 TI - Lung ultrasound versus chest radiography for the diagnosis of pneumothorax in critically ill patients: A prospective, single-blind study. AB - BACKGROUND: Radiologic data remains the gold standard for the diagnosis of pneumothorax (PTX). The use of ultrasonography (US) has recently emerged as the method of choice with physicians who can perform bedside US. PURPOSE: To compare the diagnostic accuracy of lung US against bedside chest radiography (CR) for the detection of PTX using thoracic computed tomography (CT) as the gold standard. MATERIALS AND METHODS: We conducted a prospective, single-blind study on 192 critically ill patients; each patient received lung US examination, bedside CR, followed by thoracic CT scan searching for PTX. RESULTS: Of the studied patients, CT of the chest confirmed the diagnosis of PTX in 36 (18.75%) patients of which 31 were diagnosed by thoracic US while CR detected only 19 cases. Overall lung US showed a considerable higher sensitivity than bedside CR (86.1% vs. 52.7%), lung US also showed higher, negative predictive values, and diagnostic accuracy against CR (96.8% vs. 90.1%), and (95.3% vs. 90.6%), respectively. CR had a slightly higher specificity than lung US (99.4% vs. 97.4%), and higher positive predictive values (95.0% vs. 88.6%). CONCLUSION: Lung US is an accurate modality more than anteroposterior bedside CR in comparison with CT scanning when evaluating critically ill mechanically ventilated patients, patients underwent thoracocentesis, central venous catheter insertion, or patients with polytrauma. PMID- 27375380 TI - Inaccurate level of intervertebral space estimated by palpation: The ultrasonic revelation. AB - BACKGROUND: Spinal cord injury resulting from spinal anesthesia is a rare, but an alarming scenario. The most likely cause is believed to be misjudged level of intervertebral space (IVS). We evaluated the accuracy of palpation method to locate IVS with the ultrasonography. MATERIALS AND METHODS: A total of 109 patients undergoing spinal anesthesia were included in this observational, double blind study. First anesthesiologist was asked to mark IVS using palpation method. It was followed by ultrasonographic assessment by another anesthesiologist who was unaware of the level estimated for the mark. We evaluated the accuracy of palpation method in sitting and lateral position as well as the impact of the anesthesiologist's experience (Trainee/Consultant). STATISTICAL ANALYSIS USED: Association between the gender, anthropometric parameters, type of anesthesiologists assessing the IVS, and the level of agreement were identified using Chi-square test. The agreement between palpation method and ultrasound assessment of IVS was analyzed using kappa statistic. P < 0.05 was defined as statistical significance. RESULTS: The IVS located by palpation method was in agreement with ultrasound location in 37.14% of the patients. There were no statistically significant differences found in terms of demographic data (sex, age, height, weight, or body mass index [BMI]) between agreement and disagreement group. The rate of errors was found to be significantly higher (P = 0.01) among the trainees (74.51%) than the consultants (51.86%). The rate of errors was not different between the sitting and lateral position. The frequency of errors was more common in cephalad direction (53.31.5%) compared to caudal direction (9.52%). The misidentified spaces were as high as three spaces above the intended space while in caudal direction it differed by only one space. CONCLUSION: The accuracy of palpation method controlled by ultrasound is 37.14% and differs by 1 3 IVS in cephalad direction (53.31%). The accuracy is affected by anesthesiologist's experience but remains unaffected by age, sex height, BMI, and patient positioning. PMID- 27375381 TI - Controlled hypotension in day care functional endoscopic sinus surgery: A comparison between esmolol and dexmedetomidine: A prospective, double-blind, and randomized study. AB - BACKGROUND: Functional endoscopic sinus surgery (FESS) is the cornerstone of therapeutic management for nasal pathologies. This study is to compare the ability of preoperative and intraoperative esmolol versus dexmedetomidine for producing induced hypotension during FESS in adults in a day care setting. MATERIALS AND METHODS: Sixty patients (20-45 years) posted for FESS under general anesthesia were randomly divided into Group E (n = 30) receiving esmolol, loading dose 1 mg/kg over 1 min followed by 0.5 mg/kg/h infusion during maintenance and Group D (n = 30) receiving dexmedetomidine 1 MUg/kg over 15 min before induction of anesthesia followed by 0.5 MUg/Kg/h infusion during maintenance, respectively. Nasal bleeding and Surgeon's satisfaction score; amount and number of patients receiving fentanyl and nitroglycerine for analgesia and deliberate hypotension, Postanesthesia Care Unit (PACU) and hospital stay; hemodynamic parameters and side effects were recorded for each patient. RESULTS: Significantly less number and dosage of nitroglycerine was required (P = 0.0032 and 0.0001, respectively) in Group D compared to that in Group E. Again the number and dosage of patients requiring fentanyl were significantly lower in Group D. However, the duration of controlled hypotension was almost similar in both the groups. Group D patients suffered from significantly less nasal bleeding, and surgeon's satisfaction score was also high in this group. Discharge from PACU and hospital were significantly earlier in Group D. Intraoperative hemodynamics were quite comparable (P > 0.05) without any appreciable side effects. CONCLUSION: Dexmedetomidine found to be providing more effectively controlled hypotension and analgesia and thus allowing less nasal bleeding as well as more surgeons' satisfaction score. PMID- 27375382 TI - Arthroscopic medial meniscus trimming or repair under nerve blocks: Which nerves should be blocked? AB - BACKGROUND: This study aimed to determine the role of the sciatic and obturator nerve blocks (in addition to femoral block) in providing painless arthroscopic medial meniscus trimming/repair. MATERIALS AND METHODS: One hundred and twenty patients with medial meniscus tear, who had been scheduled to knee arthroscopy, were planned to be included in this controlled prospective double-blind study. The patients were randomly allocated into three equal groups; FSO, FS, and FO. The femoral, sciatic, and obturator nerves were blocked in FSO groups. The femoral and sciatic nerves were blocked in FS group, while the femoral and obturator nerves were blocked in FO group. Intraoperative pain and its causative surgical maneuver were recorded. RESULTS: All the patients (n = 7, 100%) in FO group had intraoperative pain. The research was terminated in this group but completed in FS and FSO groups (40 patients each). During valgus positioning of the knee for surgical management of the medial meniscus tear, the patients in FS group experienced pain more frequently than those in FSO group (P = 0.005). CONCLUSION: Adding a sciatic nerve block to the femoral nerve block is important for painless knee arthroscopy. Further adding of an obturator nerve block may be needed when a valgus knee position is required to manage the medial meniscus tear. PMID- 27375383 TI - Intraoperative effect of dexmedetomidine infusion during living donor liver transplantation: A randomized control trial. AB - BACKGROUND: Dexmedetomidine hydrochloride (Dex) is a useful adjuvant for general anesthesia. The aim was to evaluate the effects of Dex infusion during living donors liver transplantation (LDLT) on the general anesthetic requirements, hemodynamics, oxygen consumption (VO2), and CO2 production (VCO2). MATERIALS AND METHODS: Forty LDLT recipients were allocated randomly to receive either Dex (0.2 0.7 MUg/kg/h) or placebo (control [C]). Patient state index (PSI), SEDLine monitored anesthesia depth (25-50) with desflurane (Des) % and fentanyl altered accordingly. Transesophageal Doppler (TED), invasive mean arterial blood pressure (MAP) and heart rate (HR) were monitoring any Dex side effects and altering infusion rate accordingly; TED was used for fluid optimization. Metabolic gas monitoring (VO2, VCO2) and Des consumption were recorded. RESULTS: Dex reduced Des and fentanyl consumption versus C (120.0 +/- 30.2 vs. 248.0 +/- 38.8) ml, (440.0 +/- 195.74 vs. 1300.0 +/- 32) MUg, respectively (P < 0.01). Dex was delivered for 11.35 +/- 2.45 h with comparable HR, MAP, and TED variables versus C and with similar mean noradrenaline support (5.63 +/- 2.44 vs. 5.83 +/- 2.57 mg, P = 0.81). VO2 was reduced with Dex vs. C during anhepatic, 30 min postreperfusion and end of surgery (193.2 +/- 26.78 vs. 239 +/- 14.93) (172.1 +/- 28.14 vs. 202.7 +/- 18.03) and (199.7 +/- 26.63 vs. 283.8 +/- 14.83) ml/min/m(2) respectively (P < 0.01). VCO2 was also reduced with Dex versus C during the same periods (195.2 +/- 46.41 vs. 216.7 +/- 29.90, P = 0.09), (210.6 +/- 60.71 vs. 253.9 +/- 32.51, P = 0.01), and (158.7 +/- 49.96 vs. 209.7 +/- 16.78, P < 0.01), ml/min/m(2) respectively. CONCLUSION: TED and PSI guided Dex infusion helped to reduce Des and fentanyl consumption as well as VO2 and VCO2 at a lower cost with no adverse effects on hemodynamics. PMID- 27375384 TI - Ease of insertion of the laryngeal mask airway in pediatric surgical patients: Predictors of failure and outcome. AB - BACKGROUND: Laryngeal mask airway (LMA) is an useful alternative to endotracheal tube for airway management. The risk of life-threatening adverse respiratory events during its use is rare, but we need to know about the risk-adjusted prediction of its insertion failure requiring rescue tracheal intubation and its impact on patient outcome. MATERIALS AND METHODS: Five hundred patients; 6 months to 12-year-old, American Society of Anesthesiologists I and II scheduled to undergo elective surgical procedures that require general anesthesia were included in this study. LMA was inserted after induction of anesthesia. The insertion conditions, intra, and postoperative events were recorded. Our primary outcome variable was trial success from the first time. RESULTS: We recorded 426 cases (85.2%) of first trial success with clear airway compared to 46 case (9.2%) of second trial success (P <= 0.001). Predictors of failure of first attempt of LMA insertion include abnormal airway anatomy (91%), body weight <16 kg and age below 5 years (44%), the use of LMA size of 1 and 1.5 (3.8%), the intraoperative lateral position (3.8%). CONCLUSION: The data obtained from this study support the use of the LMA as a reliable pediatric supraglottic airway device, demonstrating relatively low failure rates. Predictors of LMA failure in the pediatric surgical population should be independently considered. TRIAL REGISTRATION: The study is registered in the Australian and New Zealand clinical trial registry with the allocated trial number: ACTRN12614000994684. Web address of trial: http://www.ANZCTR.org.au/A CTRN12614000994684.aspx. PMID- 27375385 TI - Comparative effect of propofol versus sevoflurane on renal ischemia/reperfusion injury after elective open abdominal aortic aneurysm repair. AB - BACKGROUND: Renal injury is a common cause of morbidity and mortality after elective abdominal aortic aneurysm (AAA) repair. Propofol has been reported to protect several organs from ischemia/reperfusion (I/R) induced injury. We performed a randomized clinical trial to compare propofol and sevoflurane for their effects on renal I/R injury in patients undergoing elective AAA repair. MATERIALS AND METHODS: Fifty patients scheduled for elective AAA repair were randomized to receive propofol anesthesia in group I or sevoflurane anesthesia in group II. Urinary specific kidney proteins (N-acetyl-beta-glucosamidase, alpha-1 microglobulin, glutathione transferase [GST]-pi, GST-alpha) were measured within 5 min of starting anesthesia as a base line (T0), at the end of surgery (T1), 8 h after surgery (T2), 16 h after surgery (T3), and 24 h postoperatively (T4). Serum pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin 1-beta) were measured at the same time points. In addition, serum creatinine and cystatin C were measured before starting surgery as a baseline and at days 1, 3, and 6 after surgery. RESULTS: Postoperative urinary concentrations of all measured kidney specific proteins and serum pro-inflammatory cytokines were significantly lower in the propofol group. In addition, the serum creatinine and cystatin C were significantly lower in the propofol group compared with the sevoflurane group. CONCLUSION: Propofol significantly reduced renal injury after elective open AAA repair and this could have clinical implications in situations of expected renal I/R injury. PMID- 27375386 TI - Comparison of erythromycin versus metoclopramide for gastric feeding intolerance in patients with traumatic brain injury: A randomized double-blind study. AB - BACKGROUND: No randomized controlled trial demonstrates the efficacy of erythromycin or metoclopramide in patients with traumatic brain injury (TBI). This study was conducted to determine the efficacy of metoclopramide and erythromycin for improving gastric aspirate volume (GAV) in patients with TBI. MATERIALS AND METHODS: Patients with Glasgow coma score more than 5 admitted to trauma Intensive Care Unit within 72 h of head injury were assessed for eligibility. 115 patients were prospectively randomized to receive metoclopramide, erythromycin, or placebo eighth hourly. Gastric feeding intolerance was defined as GAV more than 150 ml with abdominal symptoms. Two consecutive high GAV was defined as feeding failure. Feeding failure was treated by increasing the frequency of dose to 6 hourly in metoclopramide and erythromycin group. Combination therapy with both drugs was given as rescue in the placebo group. RESULTS: Incidence of high GAV was as high as 60.5% in placebo group. Use of erythromycin was associated with a decrease in the incidence of feeding intolerance to 28.9% (P = 0.006). Although feed intolerance decreased to 43.6% in metoclopramide group, values did not reach statistical significance. The proportion of patients not having high GAV at different days were significantly higher in erythromycin group (P = 0.027, log-rank test). There was no difference in the proportion of patients not having feeding failure in three groups with increasing number of days. CONCLUSION: There was a significant decrease in the incidence of high GAV with the use of erythromycin when compared to metoclopramide and placebo. PMID- 27375387 TI - Sonographic detection of tracheal or esophageal intubation: A cadaver study. AB - BACKGROUND: The correct position of the endotracheal tube is confirmed by various modalities, most of which are not entirely reliable. Ultrasound is now increasingly available to anesthesiologists in the operating theater and is an attractive alternative. To investigate the usefulness of sonography in identifying the correct tracheal tube position in human cadavers. MATERIALS AND METHODS: Endotracheal tubes placed randomly into trachea or esophagus was identified with a linear ultrasound probe placed transversely just above the suprasternal notch by a single anesthesiologist. RESULTS: Of the 100 intubations performed at random, 99 were correctly identified to give a sensitivity of 100% and a specificity of 97.9%. CONCLUSION: Sonography is a useful technique to identify correct position of the tracheal tube. PMID- 27375388 TI - Fear of going under general anesthesia: A cross-sectional study. AB - OBJECTIVES: Fears related to anesthesia have affected a considerable number of patients going for surgery. The purpose of this survey was to identify the most common concerns about general anesthesia during the preoperative anesthetic clinic in different healthcare settings, and whether they are affected by patients' sex, age, education, or previous experience of anesthesia or not. MATERIALS AND METHODS: Structured questionnaires with consent forms were distributed to patients in their preanesthesia clinic visit in three tertiary hospitals (King Abdul-Aziz Medical City, King Faisal Specialist Hospital, and King Khalid University Hospital) in Riyadh, Saudi Arabia. Patients' demographics and questions related to their fears regarding general anesthesia were included in the questionnaires. All categorical and interval variables were compared statically using a Chi-square test for independence and a t-test, respectively. All statistical tests were declared significant at alpha level of 0.05 or less. RESULTS: Among 450 questionnaires that were disturbed, 400 questionnaires were collected and analyzed. Eighty-eight percent experienced preoperative fear. The top three causes of their fears were fear of postoperative pain (77.3%), fear of intraoperative awareness (73.7%), and fear of being sleepy postoperatively (69.5%). Patients are less fearful of drains and needles in the operative theater (48%), of revealing personal issues under general anesthesia (55.2%), and of not waking up after surgery (56.4%). Age and gender were significant predictors of the overall fear among preanesthetic patients. Females are 5 times more likely to experience fear before surgery (P = 0.0009). Patients aged more than 40 years old are also at 75% higher risk of being afraid (P = 0.008). CONCLUSION: The majority of the patients going for surgery experienced a fear of anesthesia. Mostly females, especially those over 40, were at a higher risk of being afraid. Fear can bring anxiety which, in turn, might affect the patient's surgery. PMID- 27375389 TI - Efficacy of epidural local anesthetic and dexamethasone in providing postoperative analgesia: A meta-analysis. AB - BACKGROUND: Dexamethasone is a potent anti-inflammatory, analgesic, and antiemetic drug. Individual randomized controlled trials found a possible benefit of epidural dexamethasone. The purpose of this meta-analysis is to estimate the benefit of epidural dexamethasone on postoperative pain and opioid consumption and to formulate a recommendation for evidence-based practice. MATERIALS AND METHODS: Prospective, randomized controlled trials comparing the analgesic efficacy of epidural local anesthetic and dexamethasone combination, with local anesthetic alone for postoperative pain management after abdominal surgery, were planned to be included in this meta-analysis. PubMed, PubMed Central, Scopus, and Central Register of Clinical Trials of the Cochrane Collaboration (CENTRAL) databases were searched for eligible controlled trials using the following search words: "Epidural", "dexamethasone", and "postoperative pain", until February 20, 2015. RESULTS: Data from five randomized control trials have been included in this meta-analysis. Epidural dexamethasone significantly decreased postoperative morphine consumption (mean difference -7.89 mg; 95% confidence interval [CI]: 11.66 to -3.71) and number of patients required postoperative rescue analgesic boluses (risk ratio: 0.51; 95% CI: 0.41-0.63). CONCLUSION: The present data shows that the addition of dexamethasone to local anesthetic in epidural is beneficial for postoperative pain management. PMID- 27375390 TI - Basic concepts for sample size calculation: Critical step for any clinical trials! AB - Quality of clinical trials has improved steadily over last two decades, but certain areas in trial methodology still require special attention like in sample size calculation. The sample size is one of the basic steps in planning any clinical trial and any negligence in its calculation may lead to rejection of true findings and false results may get approval. Although statisticians play a major role in sample size estimation basic knowledge regarding sample size calculation is very sparse among most of the anesthesiologists related to research including under trainee doctors. In this review, we will discuss how important sample size calculation is for research studies and the effects of underestimation or overestimation of sample size on project's results. We have highlighted the basic concepts regarding various parameters needed to calculate the sample size along with examples. PMID- 27375391 TI - Placenta accreta and anesthesia: A multidisciplinary approach. AB - Placenta accreta (an abnormally adherent placenta) is one of the two leading causes of peripartum hemorrhage and the most common indication for peripartum hysterectomy. Placenta accreta may be associated with significant maternal hemorrhage at delivery owing to the incomplete placental separation. When placenta accreta is diagnosed before delivery, a multidisciplinary approach may improve patient outcome. PMID- 27375392 TI - Anesthetic management of Amplatzer atrial septal defect closure device embolization to right ventricular outflow tract. AB - Percutaneous device closure of atrial septal defect (ASD) is an alternative treatment to surgery with advantages of avoidance of surgery, short procedure time, early discharge from hospital, and lower rates of complications. However, percutaneous device closure is associated with infrequent life-threatening complications such as device embolization. We report a case device embolization of the ASD occlude device into right ventricular outflow tract resulting progressive hypoxia. The role of anesthesiologist as a team leader in managing such emergency is discussed. PMID- 27375393 TI - Premedication in an autistic, combative child: Challenges and nuances. AB - Children with autistic spectrum disorders are often encountered in anesthesia practice mainly for outdoor procedural sedation or anesthesia in endoscopy and magnetic resonance imaging suites. We describe a case of a 7-year-old autistic boy who required management of dental caries. He had a phobia to intravenous cannulation, displayed increasing anxiety and became combative on the day of surgery. With parental involvement and distraction, we succeeded in giving oral midazolam by concealing it, with the intent of avoiding intramuscular injection or unnecessary restraint. Lack of knowledge about the medical condition of such a patient can lead to inadequate preoperative preparation and use of restraint on the patient, which might cause anxiety or panic attacks in the operative room. To effectively manage children with special needs one needs to have clear guidelines on the management of uncooperative children, involve parents perioperatively, plan ahead with an emphasis on perioperative analgesia and sometimes incorporate the ethical use of restraint. PMID- 27375394 TI - An accidental intra-arterial injection of phenytoin in a 43-year-old woman. AB - We report an accidental intra-arterial injection of phenytoin in a 43-year-old woman undergoing ventriculoperitoneal shunt for hydrocephalus. To flush the arterial line with heparin, mistakenly phenytoin was injected which caused cutaneous gangrene along the radial side of the forearm and an absence of pulsation in the radial artery. After flushing the artery with normal saline and lidocaine, the patient was transferred to the Intensive Care Unit. There the patient was put on intravenous heparin that resolved the problem leading to complete recovery of the patient. The case is being reported to emphasize the importance of close surveillance in injecting drugs through the arterial line access. PMID- 27375395 TI - Inadvertent intrathecal injection of labetalol. AB - Labetalol is a combined alpha and beta adrenergic receptor blocker. It is used to treat hypertension, especially in pregnant patients. We report a case of a female patient who was given labetalol intrathecally in place of bupivacaine due to a similar appearance of ampoules which resulted in a drop in blood pressure and pulse rate. The patient responded to fluid resuscitation and there occurred no neurological sequelae. PMID- 27375396 TI - Novel use of epidural catheter: Air injection for neuroprotection during radiofrequency ablation of spinal osteoid osteoma. AB - Osteoid osteoma (OO) is a benign bone tumor, with a male-female ratio of approximately 2:1 and mainly affecting long bones. Ten percent of the lesions occur in the spine, mostly within the posterior elements. Treatment options for OO include surgical excision and percutaneous imaging-guided radiofrequency ablation (RFA). Lesions within the spine have an inherent risk of thermal damage to the vital structure because of proximity to the neural elements. We report a novel use of the epidural catheter for air injection for the neuroprotection of nerves close to the OO of the spine. A 12-year-old and 30 kg male child with an OO of the L3 vertebra was taken up for RFA. His preoperative examinations were within normal limits. The OO was very close to the L3 nerve root. Under general anesthesia, lumbar epidural catheter was placed in the L3-L4 space under imaging guidance. Ten ml of aliquots of air was injected under imaging guidance to avoid injury to the neural structures due to RFA. The air created a gap between neural elements and the tumor and served as an insulating material thereby protecting the neural elements from damage due to the RFA. Postoperatively, the patient did not develop any neurological deficit. PMID- 27375397 TI - Multiple pterygium syndrome: Challenge for anesthesiologist. AB - Multiple pterygium syndrome (MPS) is a very rare autosomal recessive disorder characterized by flexion of joint and digit contractures, skin webbing, cleft palate, deformity of the spine, and cervical spine fusion. Difficult airway is associated mainly due to micrognathia, retrognathia, webbing of the neck, and limitation of the mouth opening and neck extension. We are reporting a case of a 5-year-old female diagnosed with MPS and exhibiting a bilateral club foot and congenital vertical talus. The patient was posted for manipulation and above the knee casting under general anesthesia. PMID- 27375398 TI - Malignant hyperthermia in a 6-month-old infant. AB - Malignant hyperthermia (MH) is a rare hypermetabolic disorder of skeletal muscles that manifests as a life-threatening crisis in susceptible individuals, after exposure to triggering agents, most commonly halothane and succinylcholine. MH presents with multiple nonspecific signs and laboratory findings such as tachycardia, hyperthermia, hypercarbia, acidosis, and muscle rigidity. Caffeine halothane contracture test is not available at most centers in India. Larach et al. have described a clinical grading scale for determining the MH raw score based on clinical findings and biochemical tests. The high degree of suspicion, early recognition and aggressive treatment should commence immediately. It is imperative to avoid triggering agents, such as volatile anesthetics and succinylcholine, and promote the use of total intravenous anesthesia in MH susceptible patients. We report a case of 6-month-old child undergoing laparotomy under general anesthesia, who presented with signs and symptoms of MH, had MH rank 5 and raw score 36. PMID- 27375399 TI - Anesthetic management of vallecular cyst excision in an infant: An airway challenge. AB - Vallecular cyst is uncommon but well-recognized cause of upper airway obstruction in newborn and infants. We hereby present anesthetic management of a case of vallecular cyst in an infant posted for excision and marsupialization. A 4-month old female infant weighing 3.5 kg presented with inspiratory stridor progressively worsening over 2 months. Anesthesia plan was to carry out inhalational induction maintaining spontaneous respiration and keeping tracheostomy as standby option. In this case, laryngoscopy was challenging due to the size and extent of the cyst thus necessitating gentle laryngoscopy to prevent cyst rupture and pulmonary aspiration. On performing laryngoscopy, epiglottis was not visualized, which made intubation difficult. At the end of surgery, extubation was not carried out as the possibility of laryngomalacia could not be eliminated and also in view of intraoperative airway manipulation. The patient was electively ventilated postoperatively and extubated on the 2(nd) postoperative day. PMID- 27375400 TI - A case of bronchiectasis needing lung isolation for cerebello pontine angle tumor excision: Anesthetic challenges. AB - The main goals of neuroanesthesia are the maintenance of adequate cerebral perfusion pressure, avoidance of hypercarbia, hypoxemia, and to provide better brain relaxation. Providing anesthesia for a patient with bronchiectasis needing lung isolation for craniotomy can be challenging. A 56-year-old male patient, case of right lung bronchiectasis with a right cerebello pontine angle tumor underwent excision in the left lateral position. Since he had severe bronchiectasis of the right lung, we had isolated the right lung using right sided double lumen tube to avoid spillage. Intraoperative split lung test was performed to assess the right lung contribution on carbon dioxide (CO2) elimination and found that there was a significant contribution from the right lung. Hence, both lungs were ventilated to control CO2. The importance of lung isolation to prevent spillage and avoidance of one lung ventilation to control the arterial CO2 are highlighted in this case report. By providing a balanced anesthetic keeping both, the neurosurgical and thoracic concerns are important for better postoperative outcome. PMID- 27375401 TI - Copper-T, an unusual cause of profuse bleeding during cesarean section. PMID- 27375402 TI - Shoulder soreness due to shoulder braces following robotic surgery in steep Trendelenburg position. PMID- 27375403 TI - Complete recovery after cardiopulmonary resuscitation in the lateral decubitus position: A report of two cases. PMID- 27375404 TI - H1N1 with adult respiratory distress syndrome for emergency lower segment cesarean section: A case report. PMID- 27375405 TI - Effect of Task-Correlated Physiological Fluctuations and Motion in 2D and 3D Echo Planar Imaging in a Higher Cognitive Level fMRI Paradigm. AB - PURPOSE: To compare 2D and 3D echo-planar imaging (EPI) in a higher cognitive level fMRI paradigm. In particular, to study the link between the presence of task-correlated physiological fluctuations and motion and the fMRI contrast estimates from either 2D EPI or 3D EPI datasets, with and without adding nuisance regressors to the model. A signal model in the presence of partly task-correlated fluctuations is derived, and predictions for contrast estimates with and without nuisance regressors are made. MATERIALS AND METHODS: Thirty-one healthy volunteers were scanned using 2D EPI and 3D EPI during a virtual environmental learning paradigm. In a subgroup of 7 subjects, heart rate and respiration were logged, and the correlation with the paradigm was evaluated. FMRI analysis was performed using models with and without nuisance regressors. Differences in the mean contrast estimates were investigated by analysis-of-variance using Subject, Sequence, Day, and Run as factors. The distributions of group level contrast estimates were compared. RESULTS: Partially task-correlated fluctuations in respiration, heart rate and motion were observed. Statistically significant differences were found in the mean contrast estimates between the 2D EPI and 3D EPI when using a model without nuisance regressors. The inclusion of nuisance regressors for cardiorespiratory effects and motion reduced the difference to a statistically non-significant level. Furthermore, the contrast estimate values shifted more when including nuisance regressors for 3D EPI compared to 2D EPI. CONCLUSION: The results are consistent with 3D EPI having a higher sensitivity to fluctuations compared to 2D EPI. In the presence partially task-correlated physiological fluctuations or motion, proper correction is necessary to get expectation correct contrast estimates when using 3D EPI. As such task-correlated physiological fluctuations or motion is difficult to avoid in paradigms exploring higher cognitive functions, 2D EPI seems to be the preferred choice for higher cognitive level fMRI paradigms. PMID- 27375406 TI - Edrophonium Challenge Test for Blepharospasm. AB - BACKGROUND: Blepharospasm is typically diagnosed by excluding any secondary diseases and neuropsychiatric disorders, as specific tests for blepharospasm are currently unavailable. Since anticholinergic agents are used to improve the symptoms of dystonia, we hypothesized that edrophonium chloride, an acetylcholinesterase inhibitor, may make the symptoms of dystonia more apparent. Therefore, we examined whether an edrophonium challenge test would be useful for diagnosing blepharospasm. METHODS: We studied 10 patients with blepharospasm and 10 with hemifacial spasms (as disease controls). We administered edrophonium and saline in this double-blind study. Before and after the injection, we recorded the clinical signs using a video camera to assess the objective symptoms every 2 min. Ten minutes after the isotonic sodium chloride and edrophonium injections, the patients evaluated their subjective signs using a visual analog scale (VAS). The objective signs on the video recordings were scored by specialists who were blind to the treatment. RESULTS: The subjective and objective signs of the patients with blepharospasm were amplified by edrophonium. In contrast, the signs in patients with hemifacial spasms were not changed by the edrophonium challenge test. CONCLUSIONS: The edrophonium challenge test may be used to diagnose blepharospasm. The study was registered with a ICMJE recognized registry, the UMIN-CTR, with the number UMIN000022557. PMID- 27375407 TI - In utero and Lactational Exposure to Acetamiprid Induces Abnormalities in Socio Sexual and Anxiety-Related Behaviors of Male Mice. AB - Neonicotinoids, a widely used group of pesticides designed to selectively bind to insect nicotinic acetylcholine receptors, were considered relatively safe for mammalian species. However, they have been found to activate vertebrate nicotinic acetylcholine receptors and could be toxic to the mammalian brain. In the present study, we evaluated the developmental neurotoxicity of acetamiprid (ACE), one of the most widely used neonicotinoids, in C57BL/6J mice whose mothers were administered ACE via gavage at doses of either 0 mg/kg (control group), 1.0 mg/kg (low-dose group), or 10.0 mg/kg (high-dose group) from gestational day 6 to lactation day 21. The results of a battery of behavior tests for socio-sexual and anxiety-related behaviors, the numbers of vasopressin-immunoreactive cells in the paraventricular nucleus of the hypothalamus, and testosterone levels were used as endpoints. In addition, behavioral flexibility in mice was assessed in a group housed environment using the IntelliCage, a fully automated mouse behavioral analysis system. In adult male mice exposed to ACE at both low and high doses, a significant reduction of anxiety level was found in the light-dark transition test. Males in the low-dose group also showed a significant increase in sexual and aggressive behaviors. In contrast, neither the anxiety levels nor the sexual behaviors of females were altered. No reductions in the testosterone level, the number of vasopressin-immunoreactive cells, or behavioral flexibility were detected in either sex. These results suggest the possibility that in utero and lactational ACE exposure interferes with the development of the neural circuits required for executing socio-sexual and anxiety-related behaviors in male mice specifically. PMID- 27375408 TI - Longitudinal Analysis of Image Time Series with Diffeomorphic Deformations: A Computational Framework Based on Stationary Velocity Fields. AB - We propose and detail a deformation-based morphometry computational framework, called Longitudinal Log-Demons Framework (LLDF), to estimate the longitudinal brain deformations from image data series, transport them in a common space and perform statistical group-wise analyses. It is based on freely available software and tools, and consists of three main steps: (i) Pre-processing, (ii) Position correction, and (iii) Non-linear deformation analysis. It is based on the LCC log Demons non-linear symmetric diffeomorphic registration algorithm with an additional modulation of the similarity term using a confidence mask to increase the robustness with respect to brain boundary intensity artifacts. The pipeline is exemplified on the longitudinal Open Access Series of Imaging Studies (OASIS) database and all the parameters values are given so that the study can be reproduced. We investigate the group-wise differences between the patients with Alzheimer's disease and the healthy control group, and show that the proposed pipeline increases the sensitivity with no decrease in the specificity of the statistical study done on the longitudinal deformations. PMID- 27375410 TI - EEG Responses to Auditory Stimuli for Automatic Affect Recognition. AB - Brain state classification for communication and control has been well established in the area of brain-computer interfaces over the last decades. Recently, the passive and automatic extraction of additional information regarding the psychological state of users from neurophysiological signals has gained increased attention in the interdisciplinary field of affective computing. We investigated how well specific emotional reactions, induced by auditory stimuli, can be detected in EEG recordings. We introduce an auditory emotion induction paradigm based on the International Affective Digitized Sounds 2nd Edition (IADS-2) database also suitable for disabled individuals. Stimuli are grouped in three valence categories: unpleasant, neutral, and pleasant. Significant differences in time domain domain event-related potentials are found in the electroencephalogram (EEG) between unpleasant and neutral, as well as pleasant and neutral conditions over midline electrodes. Time domain data were classified in three binary classification problems using a linear support vector machine (SVM) classifier. We discuss three classification performance measures in the context of affective computing and outline some strategies for conducting and reporting affect classification studies. PMID- 27375409 TI - Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging. AB - Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition's impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition-from entire diets to specific nutrients-affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i) methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns (NBPs), along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI). By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging. PMID- 27375411 TI - The First World Congress on Tourette Syndrome and Tic Disorders: Controversies and Hot Topics in Etiology and Treatment. AB - The first World Congress on Tourette Syndrome and Tic Disorders was held in London, June 2016 by the Tourette Association of America, Tourettes Action (UK), and the European Society for the Study of Tourette Syndrome. Presentations arising from large-scale collaborative projects were an important component of the scientific programme. This article focuses on areas raised in the hot topics session and two moderated debates, which covered emerging research in etiology and treatment. The hot topics ranged across genetics, arguably including the first confirmed Tourette Syndrome (TS) susceptibility gene NRXN1, neurocognition, and neurophysiology, including the possibility of a neurocognitive endophenotype for TS and the use of depth and cortical surface electrodes to investigate the neurophysiology of tics on the background of the evolving field of deep brain stimulation (DBS), to novel treatment approaches such as dental orthotics and an online behavioral intervention. The debates aired controversies in treatment; pharmacotherapy vs. behavioral treatment and the place of medical cannabinoids. These sessions demonstrate the vibrancy of a field that has considerably expanded in the last decade, the significant progress that has been made, and the direction that some of the most fruitful next phases of research will take. PMID- 27375412 TI - Microstructure Informed Tractography: Pitfalls and Open Challenges. AB - One of the major limitations of diffusion MRI tractography is that the fiber tracts recovered by existing algorithms are not truly quantitative. Local techniques for estimating more quantitative features of the tissue microstructure exist, but their combination with tractography has always been considered intractable. Recent advances in local and global modeling made it possible to fill this gap and a number of promising techniques for microstructure informed tractography have been suggested, opening new and exciting perspectives for the quantification of brain connectivity. The ease-of-use of the proposed solutions made it very attractive for researchers to include such advanced methods in their analyses; however, this apparent simplicity should not hide some critical open questions raised by the complexity of these very high-dimensional problems, otherwise some fundamental issues may be pushed into the background. The aim of this article is to raise awareness in the diffusion MRI community, notably researchers working on brain connectivity, about some potential pitfalls and modeling choices that make the interpretation of the outcomes from these novel techniques rather cumbersome. Through a series of experiments on synthetic and real data, we illustrate practical situations where erroneous and severely biased conclusions may be drawn about the connectivity if these pitfalls are overlooked, like the presence of partial/missing/duplicate fibers or the critical importance of the diffusion model adopted. Microstructure informed tractography is a young but very promising technology, and by acknowledging its current limitations as done in this paper, we hope our observations will trigger further research in this direction and new ideas for truly quantitative and biologically meaningful analyses of the connectivity. PMID- 27375414 TI - More Feedback Is Better than Less: Learning a Novel Upper Limb Joint Coordination Pattern with Augmented Auditory Feedback. AB - Motor learning is a process whereby the acquisition of new skills occurs with practice, and can be influenced by the provision of feedback. An important question is what frequency of feedback facilitates motor learning. The guidance hypothesis assumes that the provision of less augmented feedback is better than more because a learner can use his/her own inherent feedback. However, it is unclear whether this hypothesis holds true for all types of augmented feedback, including for example sonified information about performance. Thus, we aimed to test what frequency of augmented sonified feedback facilitates the motor learning of a novel joint coordination pattern. Twenty healthy volunteers first reached to a target with their arm (baseline phase). We manipulated this baseline kinematic data for each individual to create a novel target joint coordination pattern. Participants then practiced to learn the novel target joint coordination pattern, receiving either feedback on every trial i.e., 100% feedback (n = 10), or every other trial, i.e., 50% feedback (n = 10; acquisition phase). We created a sonification system to provide the feedback. This feedback was a pure tone that varied in intensity in proportion to the error of the performed joint coordination relative to the target pattern. Thus, the auditory feedback contained information about performance in real-time (i.e., "concurrent, knowledge of performance feedback"). Participants performed the novel joint coordination pattern with no-feedback immediately after the acquisition phase (immediate retention phase), and on the next day (delayed retention phase). The root-mean squared error (RMSE) and variable error (VE) of joint coordination were significantly reduced during the acquisition phase in both 100 and 50% feedback groups. There was no significant difference in VE between the groups at immediate and delayed retention phases. However, at both these retention phases, the 100% feedback group showed significantly smaller RMSE than the 50% group. Thus, contrary to the guidance hypothesis, our findings suggest that the provision of more, concurrent knowledge of performance auditory feedback during the acquisition of a novel joint coordination pattern, may result in better skill retention. PMID- 27375415 TI - Shielded Coaxial Optrode Arrays for Neurophysiology. AB - Recent progress in the study of the brain has been greatly facilitated by the development of new tools capable of minimally-invasive, robust coupling to neuronal assemblies. Two prominent examples are the microelectrode array (MEA), which enables electrical signals from large numbers of neurons to be detected and spatiotemporally correlated, and optogenetics, which enables the electrical activity of cells to be controlled with light. In the former case, high spatial density is desirable but, as electrode arrays evolve toward higher density and thus smaller pitch, electrical crosstalk increases. In the latter, finer control over light input is desirable, to enable improved studies of neuroelectronic pathways emanating from specific cell stimulation. Here, we introduce a coaxial electrode architecture that is uniquely suited to address these issues, as it can simultaneously be utilized as an optical waveguide and a shielded electrode in dense arrays. Using optogenetically-transfected cells on a coaxial MEA, we demonstrate the utility of the architecture by recording cellular currents evoked from optical stimulation. We also show the capability for network recording by radiating an area of seven individually-addressed coaxial electrode regions with cultured cells covering a section of the extent. PMID- 27375413 TI - Carbon Nanomaterials Interfacing with Neurons: An In vivo Perspective. AB - Developing new tools that outperform current state of the art technologies for imaging, drug delivery or electrical sensing in neuronal tissues is one of the great challenges in neurosciences. Investigations into the potential use of carbon nanomaterials for such applications started about two decades ago. Since then, numerous in vitro studies have examined interactions between these nanomaterials and neurons, either by evaluating their compatibility, as vectors for drug delivery, or for their potential use in electric activity sensing and manipulation. The results obtained indicate that carbon nanomaterials may be suitable for medical therapies. However, a relatively small number of in vivo studies have been carried out to date. In order to facilitate the transformation of carbon nanomaterial into practical neurobiomedical applications, it is essential to identify and highlight in the existing literature the strengths and weakness that different carbon nanomaterials have displayed when probed in vivo. Unfortunately the current literature is sometimes sparse and confusing. To offer a clearer picture of the in vivo studies on carbon nanomaterials in the central nervous system, we provide a systematic and critical review. Hereby we identify properties and behavior of carbon nanomaterials in vivo inside the neural tissues, and we examine key achievements and potentially problematic toxicological issues. PMID- 27375416 TI - Attention Modulates the Auditory Cortical Processing of Spatial and Category Cues in Naturalistic Auditory Scenes. AB - This combined fMRI and MEG study investigated brain activations during listening and attending to natural auditory scenes. We first recorded, using in-ear microphones, vocal non-speech sounds, and environmental sounds that were mixed to construct auditory scenes containing two concurrent sound streams. During the brain measurements, subjects attended to one of the streams while spatial acoustic information of the scene was either preserved (stereophonic sounds) or removed (monophonic sounds). Compared to monophonic sounds, stereophonic sounds evoked larger blood-oxygenation-level-dependent (BOLD) fMRI responses in the bilateral posterior superior temporal areas, independent of which stimulus attribute the subject was attending to. This finding is consistent with the functional role of these regions in the (automatic) processing of auditory spatial cues. Additionally, significant differences in the cortical activation patterns depending on the target of attention were observed. Bilateral planum temporale and inferior frontal gyrus were preferentially activated when attending to stereophonic environmental sounds, whereas when subjects attended to stereophonic voice sounds, the BOLD responses were larger at the bilateral middle superior temporal gyrus and sulcus, previously reported to show voice sensitivity. In contrast, the time-resolved MEG responses were stronger for mono- than stereophonic sounds in the bilateral auditory cortices at ~360 ms after the stimulus onset when attending to the voice excerpts within the combined sounds. The observed effects suggest that during the segregation of auditory objects from the auditory background, spatial sound cues together with other relevant temporal and spectral cues are processed in an attention-dependent manner at the cortical locations generally involved in sound recognition. More synchronous neuronal activation during monophonic than stereophonic sound processing, as well as (local) neuronal inhibitory mechanisms in the auditory cortex, may explain the simultaneous increase of BOLD responses and decrease of MEG responses. These findings highlight the complimentary role of electrophysiological and hemodynamic measures in addressing brain processing of complex stimuli. PMID- 27375417 TI - Altered Onset Response Dynamics in Somatosensory Processing in Autism Spectrum Disorder. AB - Abnormalities in cortical connectivity and evoked responses have been extensively documented in autism spectrum disorder (ASD). However, specific signatures of these cortical abnormalities remain elusive, with data pointing toward abnormal patterns of both increased and reduced response amplitudes and functional connectivity. We have previously proposed, using magnetoencephalography (MEG) data, that apparent inconsistencies in prior studies could be reconciled if functional connectivity in ASD was reduced in the feedback (top-down) direction, but increased in the feedforward (bottom-up) direction. Here, we continue this line of investigation by assessing abnormalities restricted to the onset, feedforward inputs driven, component of the response to vibrotactile stimuli in somatosensory cortex in ASD. Using a novel method that measures the spatio temporal divergence of cortical activation, we found that relative to typically developing participants, the ASD group was characterized by an increase in the initial onset component of the cortical response, and a faster spread of local activity. Given the early time window, the results could be interpreted as increased thalamocortical feedforward connectivity in ASD, and offer a plausible mechanism for the previously observed increased response variability in ASD, as well as for the commonly observed behaviorally measured tactile processing abnormalities associated with the disorder. PMID- 27375418 TI - Beat Keeping in a Sea Lion As Coupled Oscillation: Implications for Comparative Understanding of Human Rhythm. AB - Human capacity for entraining movement to external rhythms-i.e., beat keeping-is ubiquitous, but its evolutionary history and neural underpinnings remain a mystery. Recent findings of entrainment to simple and complex rhythms in non human animals pave the way for a novel comparative approach to assess the origins and mechanisms of rhythmic behavior. The most reliable non-human beat keeper to date is a California sea lion, Ronan, who was trained to match head movements to isochronous repeating stimuli and showed spontaneous generalization of this ability to novel tempos and to the complex rhythms of music. Does Ronan's performance rely on the same neural mechanisms as human rhythmic behavior? In the current study, we presented Ronan with simple rhythmic stimuli at novel tempos. On some trials, we introduced "perturbations," altering either tempo or phase in the middle of a presentation. Ronan quickly adjusted her behavior following all perturbations, recovering her consistent phase and tempo relationships to the stimulus within a few beats. Ronan's performance was consistent with predictions of mathematical models describing coupled oscillation: a model relying solely on phase coupling strongly matched her behavior, and the model was further improved with the addition of period coupling. These findings are the clearest evidence yet for parity in human and non-human beat keeping and support the view that the human ability to perceive and move in time to rhythm may be rooted in broadly conserved neural mechanisms. PMID- 27375419 TI - Resting State Functional Connectivity MRI among Spectral MEG Current Sources in Children on the Autism Spectrum. AB - Social and communicative impairments are among the core symptoms of autism spectrum disorders (ASD), and a great deal of evidence supports the notion that these impairments are associated with aberrant functioning and connectivity of various cortical networks. The present study explored the links between sources of MEG amplitude in various frequency bands and functional connectivity MRI in the resting state. The goal of combining these modalities was to use sources of neural oscillatory activity, measured with MEG, as functionally relevant seed regions for a more traditional pairwise fMRI connectivity analysis. We performed a seed-based connectivity analysis on resting state fMRI data, using seed regions derived from frequency-specific amplitude sources in resting state MEG data in the same nine subjects with ASD (10-17 years of age). We then compared fMRI connectivity among these MEG-source-derived regions between participants with autism and typically developing, age-matched controls. We used a source modeling technique designed for MEG data to detect significant amplitude sources in six frequency bands: delta (2-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low gamma (30-60 Hz), and high gamma (60-120 Hz). MEG-derived source maps for each participant were co-registered in standard MNI space, and group-level source maps were obtained for each frequency. For each frequency band, the 10 largest clusters resulting from these t-tests were used as regions of interest (ROIs) for the fMRI functional connectivity analysis. Pairwise BOLD signal correlations were obtained between each pair of these ROIs for each frequency band. Each pairwise correlation was compared between the ASD and TD groups using t-tests. We also constrained these pairwise correlations to known network structures, resulting in a follow-up set of correlation matrices specific to each network we considered. Frequency-specific MEG sources had distinct patterns of fMRI resting state functional connectivity in the ASD group, but perhaps the most significant was a finding of hypoconnectivity between many sources of low and high gamma activity. These novel findings suggest that in ASD there are differences in functionally defined networks as shown in previous fMRI studies, as well as between sets of regions defined by magnetoencephalographic neural oscillatory activity. PMID- 27375420 TI - Isolation Syndrome after Cardiac Arrest and Therapeutic Hypothermia. AB - Here, we present the first description of an isolation syndrome in a patient who suffered prolonged cardiac arrest and underwent a standard therapeutic hypothermia protocol. Two years after the arrest, the patient demonstrated no motor responses to commands, communication capabilities, or visual tracking at the bedside. However, resting neuronal metabolism and electrical activity across the entire anterior forebrain was found to be normal despite severe structural injuries to primary motor, parietal, and occipital cortices. In addition, using quantitative electroencephalography, the patient showed evidence for willful modulation of brain activity in response to auditory commands revealing covert conscious awareness. A possible explanation for this striking dissociation in this patient is that altered neuronal recovery patterns following therapeutic hypothermia may lead to a disproportionate preservation of anterior forebrain cortico-thalamic circuits even in the setting of severe hypoxic injury to other brain areas. Compared to recent reports of other severely brain-injured subjects with such dissociation of clinically observable (overt) and covert behaviors, we propose that this case represents a potentially generalizable mechanism producing an isolation syndrome of blindness, motor paralysis, and retained cognition as a sequela of cardiac arrest and therapeutic hypothermia. Our findings further support that highly-preserved anterior cortico-thalamic integrity is associated with the presence of conscious awareness independent from the degree of injury to other brain areas. PMID- 27375421 TI - Weighing the Cost and Benefit of Transcranial Direct Current Stimulation on Different Reading Subskills. AB - Adults struggling with low reading skills are underserved by limited available treatments. While brain stimulation techniques such as transcranial direct current stimulation (tDCS) has the potential to improve a variety of cognitive functions, little work has been done examining its potential to treat reading disabilities. Research on the effects of tDCS on reading abilities has been somewhat inconsistent perhaps in part due to discrepancies between studies in the nature of the tasks. In the current study, we examined the effect of tDCS to the left inferior parietal lobe (L IPL) on two reading tasks in low-to-average readers. We compared performance on a sight word efficiency (SWE) task and a rhyme judgment task before and after either stimulation to the L IPL, right superior parietal lobe (R SPL), or sham stimulation. Readers who received stimulation to the L IPL showed greater improvements on the SWE task, but less improvement on the rhyme judgment task compared to the R SPL and sham groups. This study demonstrates for the first time both a positive and negative effect of stimulation under the same stimulation parameters within the same participants. The results highlight the need to consider multiple tasks when assessing the potential of using tDCS as a treatment. PMID- 27375422 TI - Multimodal 7T Imaging of Thalamic Nuclei for Preclinical Deep Brain Stimulation Applications. AB - Precise neurosurgical targeting of electrode arrays within the brain is essential to the successful treatment of a range of brain disorders with deep brain stimulation (DBS) therapy. Here, we describe a set of computational tools to generate in vivo, subject-specific atlases of individual thalamic nuclei thus improving the ability to visualize thalamic targets for preclinical DBS applications on a subject-specific basis. A sequential nonlinear atlas warping technique and a Bayesian estimation technique for probabilistic crossing fiber tractography were applied to high field (7T) susceptibility-weighted and diffusion-weighted imaging, respectively, in seven rhesus macaques. Image contrast, including contrast within thalamus from the susceptibility-weighted images, informed the atlas warping process and guided the seed point placement for fiber tractography. The susceptibility-weighted imaging resulted in relative hyperintensity of the intralaminar nuclei and relative hypointensity in the medial dorsal nucleus, pulvinar, and the medial/ventral border of the ventral posterior nuclei, providing context to demarcate borders of the ventral nuclei of thalamus, which are often targeted for DBS applications. Additionally, ascending fiber tractography of the medial lemniscus, superior cerebellar peduncle, and pallidofugal pathways into thalamus provided structural demarcation of the ventral nuclei of thalamus. The thalamic substructure boundaries were validated through in vivo electrophysiological recordings and post-mortem blockface tissue sectioning. Together, these imaging tools for visualizing and segmenting thalamus have the potential to improve the neurosurgical targeting of DBS implants and enhance the selection of stimulation settings through more accurate computational models of DBS. PMID- 27375424 TI - Third Trimester Equivalent Alcohol Exposure Reduces Modulation of Glutamatergic Synaptic Transmission by 5-HT1A Receptors in the Rat Hippocampal CA3 Region. AB - Fetal alcohol exposure has been associated with many neuropsychiatric disorders that have been linked to altered serotonin (5-hydroxytryptamine; 5-HT) signaling, including depression and anxiety. During the first 2 weeks of postnatal life in rodents (equivalent to the third trimester of human pregnancy) 5-HT neurons undergo significant functional maturation and their axons reach target regions in the forebrain (e.g., cortex and hippocampus). The objective of this study was to identify the effects of third trimester ethanol (EtOH) exposure on hippocampal 5 HT signaling. Using EtOH vapor inhalation chambers, we exposed rat pups to EtOH for 4 h/day from postnatal day (P) 2 to P12. The average serum EtOH concentration in the pups was 0.13 +/- 0.04 g/dl (legal intoxication limit in humans = 0.08 g/dl). We used brain slices to assess the modulatory actions of 5-HT on field excitatory postsynaptic potentials in the hippocampal CA3 region at P13-P15. Application of the GABAA/glycine receptor antagonist, picrotoxin, caused broadening of field excitatory postsynaptic potentials (fEPSPs), an effect that was reversed by application of 5-HT in slices from air exposed rats. However, this effect of 5-HT was absent in EtOH exposed animals. In slices from naive animals, application of a 5-HT1A receptor antagonist blocked the effect of 5-HT on the fEPSPs recorded in presence of picrotoxin, suggesting that third trimester ethanol exposure acts by inhibiting the function of these receptors. Studies indicate that 5-HT1A receptors play a critical role in the development of hippocampal circuits. Therefore, inhibition of these receptors by third trimester ethanol exposure could contribute to the pathophysiology of fetal alcohol spectrum disorders. PMID- 27375423 TI - Drug Design for CNS Diseases: Polypharmacological Profiling of Compounds Using Cheminformatic, 3D-QSAR and Virtual Screening Methodologies. AB - HIGHLIGHTS Many CNS targets are being explored for multi-target drug designNew databases and cheminformatic methods enable prediction of primary pharmaceutical target and off-targets of compoundsQSAR, virtual screening and docking methods increase the potential of rational drug design The diverse cerebral mechanisms implicated in Central Nervous System (CNS) diseases together with the heterogeneous and overlapping nature of phenotypes indicated that multitarget strategies may be appropriate for the improved treatment of complex brain diseases. Understanding how the neurotransmitter systems interact is also important in optimizing therapeutic strategies. Pharmacological intervention on one target will often influence another one, such as the well-established serotonin-dopamine interaction or the dopamine-glutamate interaction. It is now accepted that drug action can involve plural targets and that polypharmacological interaction with multiple targets, to address disease in more subtle and effective ways, is a key concept for development of novel drug candidates against complex CNS diseases. A multi-target therapeutic strategy for Alzheimer's disease resulted in the development of very effective Multi-Target Designed Ligands (MTDL) that act on both the cholinergic and monoaminergic systems, and also retard the progression of neurodegeneration by inhibiting amyloid aggregation. Many compounds already in databases have been investigated as ligands for multiple targets in drug-discovery programs. A probabilistic method, the Parzen Rosenblatt Window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. Based on all these findings, it is concluded that multipotent ligands targeting AChE/MAO-A/MAO-B and also D1-R/D2-R/5-HT2A -R/H3-R are promising novel drug candidates with improved efficacy and beneficial neuroleptic and procognitive activities in treatment of Alzheimer's and related neurodegenerative diseases. Structural information for drug targets permits docking and virtual screening and exploration of the molecular determinants of binding, hence facilitating the design of multi-targeted drugs. The crystal structures and models of enzymes of the monoaminergic and cholinergic systems have been used to investigate the structural origins of target selectivity and to identify molecular determinants, in order to design MTDLs. PMID- 27375425 TI - The Fallacy of Univariate Solutions to Complex Systems Problems. AB - Complex biological systems, by definition, are composed of multiple components that interact non-linearly. The human brain constitutes, arguably, the most complex biological system known. Yet most investigation of the brain and its function is carried out using assumptions appropriate for simple systems univariate design and linear statistical approaches. This heuristic must change before we can hope to discover and test interventions to improve the lives of individuals with complex disorders of brain development and function. Indeed, a movement away from simplistic models of biological systems will benefit essentially all domains of biology and medicine. The present brief essay lays the foundation for this argument. PMID- 27375426 TI - Parkinson's Disease and Neurodegeneration: GABA-Collapse Hypothesis. AB - Neurodegenerative diseases constitute a heterogeneous group of age-related disorders that are characterized by a slow but irreversible deterioration of brain functions. Evidence accumulated over more than two decades has implicated calcium-related homeostatic mechanisms, giving rise to the Ca(2+) hypothesis of brain aging and, ultimately, cell death. Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter within the central (CNS), peripheral and enteric nervous systems. It appears to be involved in a wide variety of physiological functions within and outside the nervous system, that are maintained through a complex interaction between GABA and calcium-dependent neurotransmission and cellular metabolic functions. Within CNS the Ca(2+)/GABA mechanism stabilizes neuronal activity both at cellular and systemic levels. Decline in the Ca(2+)/GABA control initiates several cascading processes leading to both weakened protective barriers (in particular the blood-brain barrier) and accumulations of intracellular deposits of calcium and Lewy bodies. Linking such a vital mechanism of synaptic transmission with metabolism (both at cellular and tissue level) by means of a common reciprocal Ca(2+)/GABA inhibition results in a fragile balance, which is prone to destabilization and auto-destruction. The GABA decline etiology proposed here appears to apply to all human neurodegenerative processes initiated by abnormal intracellular calcium levels. Therefore, the original description of Parkinson's disease (PD) as due to the selective damage of dopaminergic neurons in the mesencephalon should be updated into the concept of a severe multisystemic neurodegenerative disorder of the nervous system, whose clinical symptoms reflect the localization and progression of the most advanced GABA pathology. A future and more complete therapeutic approach to PD should be aimed first at slowing (or stopping) the progression of Ca(2+)/GABA functional decline. PMID- 27375428 TI - The Enigma of the Dichotomic Pressure Response of GluN1-4a/b Splice Variants of NMDA Receptor: Experimental and Statistical Analyses. AB - Professional deep-water divers, exposed to hyperbaric pressure (HP) above 1.1 MPa, develop High Pressure Neurological Syndrome (HPNS), which is associated with central nervous system (CNS) hyperexcitability. It was previously reported that HP augments N-methyl-D-aspartate receptor (NMDAR) synaptic response, increases neuronal excitability and potentially causes irreversible neuronal damage. Our laboratory has reported differential current responses under HP conditions in NMDAR subtypes that contain either GluN1-1a or GluN1-1b splice variants co expressed in Xenopus laevis oocytes with all four GluN2 subunits. Recently, we reported that the increase in ionic currents measured under HP conditions is also dependent on which of the eight splice variants of GluN1 is co-expressed with the GluN2 subunit. We now report that the NMDAR subtype that contains GluN1-4a/b splice variants exhibited "dichotomic" (either increased or decreased) responses at HP. The distribution of the results is not normal thus analysis of variance (ANOVA) test and clustering analysis were employed for statistical verification of the grouping. Furthermore, the calculated constants of alpha function distribution analysis for the two groups were similar, suggesting that the mechanism underlying the switch between an increase or a decrease of the current at HP is a single process, the nature of which is still unknown. This dichotomic response of the GluN1-4a/b splice variant may be used as a model for studying reduced response in NMDAR at HP. Successful reversal of other NMDAR subtypes response (i.e., current reduction) may allow the elimination of the reversible malfunctioning short term effects (HPNS), or even deleterious long term effects induced by increased NMDAR function during HP exposure. PMID- 27375429 TI - Adenosine Kinase Inhibition Protects against Cranial Radiation-Induced Cognitive Dysfunction. AB - Clinical radiation therapy for the treatment of CNS cancers leads to unintended and debilitating impairments in cognition. Radiation-induced cognitive dysfunction is long lasting; however, the underlying molecular and cellular mechanisms are still not well established. Since ionizing radiation causes microglial and astroglial activation, we hypothesized that maladaptive changes in astrocyte function might be implicated in radiation-induced cognitive dysfunction. Among other gliotransmitters, astrocytes control the availability of adenosine, an endogenous neuroprotectant and modulator of cognition, via metabolic clearance through adenosine kinase (ADK). Adult rats exposed to cranial irradiation (10 Gy) showed significant declines in performance of hippocampal dependent cognitive function tasks [novel place recognition, novel object recognition (NOR), and contextual fear conditioning (FC)] 1 month after exposure to ionizing radiation using a clinically relevant regimen. Irradiated rats spent less time exploring a novel place or object. Cranial irradiation also led to reduction in freezing behavior compared to controls in the FC task. Importantly, immunohistochemical analyses of irradiated brains showed significant elevation of ADK immunoreactivity in the hippocampus that was related to astrogliosis and increased expression of glial fibrillary acidic protein (GFAP). Conversely, rats treated with the ADK inhibitor 5-iodotubercidin (5-ITU, 3.1 mg/kg, i.p., for 6 days) prior to cranial irradiation showed significantly improved behavioral performance in all cognitive tasks 1 month post exposure. Treatment with 5-ITU attenuated radiation-induced astrogliosis and elevated ADK immunoreactivity in the hippocampus. These results confirm an astrocyte-mediated mechanism where preservation of extracellular adenosine can exert neuroprotection against radiation-induced pathology. These innovative findings link radiation-induced changes in cognition and CNS functionality to altered purine metabolism and astrogliosis, thereby linking the importance of adenosine homeostasis in the brain to radiation injury. PMID- 27375430 TI - Visualizing K48 Ubiquitination during Presynaptic Formation By Ubiquitination Induced Fluorescence Complementation (UiFC). AB - In recent years, signaling through ubiquitin has been shown to be of great importance for normal brain development. Indeed, fluctuations in ubiquitin levels and spontaneous mutations in (de)ubiquitination enzymes greatly perturb synapse formation and neuronal transmission. In the brain, expression of lysine (K) 48 linked ubiquitin chains is higher at a developmental stage coincident with synaptogenesis. Nevertheless, no studies have so far delved into the involvement of this type of polyubiquitin chains in synapse formation. We have recently proposed a role for polyubiquitinated conjugates as triggering signals for presynaptic assembly. Herein, we aimed at characterizing the axonal distribution of K48 polyubiquitin and its dynamics throughout the course of presynaptic formation. To accomplish so, we used an ubiquitination-induced fluorescence complementation (UiFC) strategy for the visualization of K48 polyubiquitin in live hippocampal neurons. We first validated its use in neurons by analyzing changing levels of polyubiquitin. UiFC signal is diffusely distributed with distinct aggregates in somas, dendrites and axons, which perfectly colocalize with staining for a K48-specific antibody. Axonal UiFC aggregates are relatively stable and new aggregates are formed as an axon grows. Approximately 65% of UiFC aggregates colocalize with synaptic vesicle clusters and they preferentially appear in the axonal domains of axo-somatodendritic synapses when compared to isolated axons. We then evaluated axonal accumulation of K48 ubiquitinated signals in bead-induced synapses. We observed rapid accumulation of UiFC signal and endogenous K48 ubiquitin at the sites of newly formed presynapses. Lastly, we show by means of a microfluidic platform, for the isolation of axons, that presynaptic clustering on beads is dependent on E1-mediated ubiquitination at the axonal level. Altogether, these results indicate that enrichment of K48 polyubiquitin at the site of nascent presynaptic terminals is an important axon intrinsic event for presynaptic differentiation. PMID- 27375432 TI - Characterization of a Synaptic Vesicle Binding Motif on the Distal CaV2.2 Channel C-terminal. AB - Neurotransmitter is released from synaptic vesicles (SVs) that are gated to fuse with the presynaptic membrane by calcium ions that enter through voltage-gated calcium channels (CaVs). There is compelling evidence that SVs associate closely with the CaVs but the molecular linking mechanisms remain poorly understood. Using a cell-free, synaptic vesicle-pull-down assay method (SV-PD) we have recently demonstrated that SVs can bind both to the intact CaV2.2 channel and also to a fusion protein comprising the distal third, C3 segment, of its long C terminal. This site was localized to a 49 amino acid region just proximal to the C-terminal tip. To further restrict the SV binding site we generated five, 10 amino acid mimetic blocking peptides spanning this region. Of these, HQARRVPNGY effectively inhibited SV-PD and also inhibited SV recycling when cryoloaded into chick brain nerve terminals (synaptosomes). Further, SV-PD was markedly reduced using a C3 fusion protein that lacked the HQARRVPNGY sequence, C3HQless. We zeroed in on the SV binding motif within HQARRVPNGY by means of a palette of mutant blocking peptides. To our surprise, peptides that lacked the highly conserved VPNGY sequence still blocked SV-PD. However, substitution of the HQ and RR amino acids markedly reduced block. Of these, the RR pair was essential but not sufficient as the full block was not observed without H suggesting a CaV2.2 SV binding motif of HxxRR. Interestingly, CaV2.1, the other primary presynaptic calcium channel, exhibits a similar motif, RHxRR, that likely serves the same function. Bioinformatic analysis showed that variations of this binding motif, +(+) xRR (where + is a positively charged aa H or R), are conserved from lung fish to man. Further studies will be necessary to identify the C terminal motif binding partner on the SV itself and to determine the role of this molecular interaction in synaptic transmission. We hypothesize that the distal C-terminal participates in the capture of the SVs from the cytoplasm, initiating their delivery to the active zone where additional tethering interactions secure the vesicle within range of the CaV single Ca(2+) domains. PMID- 27375431 TI - Linking Activation of Microglia and Peripheral Monocytic Cells to the Pathophysiology of Psychiatric Disorders. AB - A wide variety of studies have identified microglial activation in psychiatric disorders, such as schizophrenia, bipolar disorder, and major depressive disorder. Relatively fewer, but robust, studies have detected activation of peripheral monocytic cells in psychiatric disorders. Considering the origin of microglia, as well as neuropsychoimmune interactions in the context of the pathophysiology of psychiatric disorders, it is reasonable to speculate that microglia interact with peripheral monocytic cells in relevance with the pathogenesis of psychiatric disorders; however, these interactions have drawn little attention. In this review, we summarize findings relevant to activation of microglia and monocytic cells in psychiatric disorders, discuss the potential association between these cell types and disease pathogenesis, and propose perspectives for future research on these processes. PMID- 27375433 TI - Corrigendum: Local Optogenetic Induction of Fast (20-40 Hz) Pyramidal-Interneuron Network Oscillations in the In Vitro and In Vivo CA1 Hippocampus: Modulation by CRF and Enforcement of Perirhinal Theta Activity. AB - [This corrects the article on p. 108 in vol. 10, PMID: 27199662.]. PMID- 27375427 TI - Regulating Axonal Responses to Injury: The Intersection between Signaling Pathways Involved in Axon Myelination and The Inhibition of Axon Regeneration. AB - Following spinal cord injury (SCI), a multitude of intrinsic and extrinsic factors adversely affect the gene programs that govern the expression of regeneration-associated genes (RAGs) and the production of a diversity of extracellular matrix molecules (ECM). Insufficient RAG expression in the injured neuron and the presence of inhibitory ECM at the lesion, leads to structural alterations in the axon that perturb the growth machinery, or form an extraneous barrier to axonal regeneration, respectively. Here, the role of myelin, both intact and debris, in antagonizing axon regeneration has been the focus of numerous investigations. These studies have employed antagonizing antibodies and knockout animals to examine how the growth cone of the re-growing axon responds to the presence of myelin and myelin-associated inhibitors (MAIs) within the lesion environment and caudal spinal cord. However, less attention has been placed on how the myelination of the axon after SCI, whether by endogenous glia or exogenously implanted glia, may alter axon regeneration. Here, we examine the intersection between intracellular signaling pathways in neurons and glia that are involved in axon myelination and axon growth, to provide greater insight into how interrogating this complex network of molecular interactions may lead to new therapeutics targeting SCI. PMID- 27375435 TI - Effects of an High-Fat Diet Enriched in Lard or in Fish Oil on the Hypothalamic Amp-Activated Protein Kinase and Inflammatory Mediators. AB - The high fat diet (HFD) rich in lard induces obesity, inflammation and oxidative stress, and the deregulation of hypothalamic nuclei plays an important role in this mechanism. One important factor involved in the food intake and inflammation is adenosine monophosphate-dependent kinase (AMPK), a serine/threonine kinase activated by phosphorylation. Omega (omega)3-polyunsaturated fatty acids (PUFA) are dietary compounds known to attenuate the obesity-related diseases, although the molecular mechanisms underlying their actions in the hypothalamus are not completely understood. We hypothesized that the beneficial effects of PUFA may be mediated by AMPK in the hypothalamus. To this aim, rats were fed a control diet (CD), or isocaloric HFD containing either fish oil (FD; rich in omega3-PUFA) or lard for 6 weeks, and the activation of AMPK, inflammatory state (IKKbeta, TNF alpha) and oxidative stress were analyzed in the hypothalamus. In addition, we also studied serum lipid profile, homeostatic model assessment (HOMA) index, and pro-inflammatory parameters. Our results showed, at the hypothalamic level of LD fed rats, an increase of AMPK activation, inflammation and oxidative stress, while no modifications were detected in FD-fed animals compared to CD. In addition body weight gain, serum lipid profile, pro-inflammatory parameters and insulin resistance were reduced in FD animals compared to LD. In conclusion, our data indicate that the substitution of saturated by unsaturated fatty acids in the diet has beneficial effects on modulation of hypothalamic inflammation and function in obesity, underlying, at hypothalamic level, the interaction among insulin and/or leptin resistance, AMPK activation and hyperphagia. PMID- 27375436 TI - Comments and General Discussion on "The Anatomical Problem Posed by Brain Complexity and Size: A Potential Solution". PMID- 27375434 TI - Long-Term Estrogen Receptor Beta Agonist Treatment Modifies the Hippocampal Transcriptome in Middle-Aged Ovariectomized Rats. AB - Estradiol (E2) robustly activates transcription of a broad array of genes in the hippocampal formation of middle-aged ovariectomized rats via estrogen receptors (ERalpha, ERbeta, and G protein-coupled ER). Selective ERbeta agonists also influence hippocampal functions, although their downstream molecular targets and mechanisms are not known. In this study, we explored the effects of long-term treatment with ERbeta agonist diarylpropionitrile (DPN, 0.05 mg/kg/day, sc.) on the hippocampal transcriptome in ovariectomized, middle-aged (13 month) rats. Isolated hippocampal formations were analyzed by Affymetrix oligonucleotide microarray and quantitative real-time PCR. Four hundred ninety-seven genes fulfilled the absolute fold change higher than 2 (FC > 2) selection criterion. Among them 370 genes were activated. Pathway analysis identified terms including glutamatergic and cholinergic synapse, RNA transport, endocytosis, thyroid hormone signaling, RNA degradation, retrograde endocannabinoid signaling, and mRNA surveillance. PCR studies showed transcriptional regulation of 58 genes encoding growth factors (Igf2, Igfb2, Igf1r, Fgf1, Mdk, Ntf3, Bdnf), transcription factors (Otx2, Msx1), potassium channels (Kcne2), neuropeptides (Cck, Pdyn), peptide receptors (Crhr2, Oprm1, Gnrhr, Galr2, Sstr1, Sstr3), neurotransmitter receptors (Htr1a, Htr2c, Htr2a, Gria2, Gria3, Grm5, Gabra1, Chrm5, Adrb1), and vesicular neurotransmitter transporters (Slc32a1, Slc17a7). Protein-protein interaction analysis revealed networking of clusters associated with the regulation of growth/troph factor signaling, transcription, translation, neurotransmitter and neurohormone signaling mechanisms and potassium channels. Collectively, the results reveal the contribution of ERbeta-mediated processes to the regulation of transcription, translation, neurogenesis, neuromodulation, and neuroprotection in the hippocampal formation of ovariectomized, middle-aged rats and elucidate regulatory channels responsible for DPN-altered functional patterns. These findings support the notion that selective activation of ERbeta may be a viable approach for treating the neural symptoms of E2 deficiency in menopause. PMID- 27375438 TI - Universal Darwinism As a Process of Bayesian Inference. AB - Many of the mathematical frameworks describing natural selection are equivalent to Bayes' Theorem, also known as Bayesian updating. By definition, a process of Bayesian Inference is one which involves a Bayesian update, so we may conclude that these frameworks describe natural selection as a process of Bayesian inference. Thus, natural selection serves as a counter example to a widely-held interpretation that restricts Bayesian Inference to human mental processes (including the endeavors of statisticians). As Bayesian inference can always be cast in terms of (variational) free energy minimization, natural selection can be viewed as comprising two components: a generative model of an "experiment" in the external world environment, and the results of that "experiment" or the "surprise" entailed by predicted and actual outcomes of the "experiment." Minimization of free energy implies that the implicit measure of "surprise" experienced serves to update the generative model in a Bayesian manner. This description closely accords with the mechanisms of generalized Darwinian process proposed both by Dawkins, in terms of replicators and vehicles, and Campbell, in terms of inferential systems. Bayesian inference is an algorithm for the accumulation of evidence-based knowledge. This algorithm is now seen to operate over a wide range of evolutionary processes, including natural selection, the evolution of mental models and cultural evolutionary processes, notably including science itself. The variational principle of free energy minimization may thus serve as a unifying mathematical framework for universal Darwinism, the study of evolutionary processes operating throughout nature. PMID- 27375437 TI - Non-image Forming Light Detection by Melanopsin, Rhodopsin, and Long-Middlewave (L/W) Cone Opsin in the Subterranean Blind Mole Rat, Spalax Ehrenbergi: Immunohistochemical Characterization, Distribution, and Connectivity. AB - The blind mole rat, Spalax ehrenbergi, can, despite severely degenerated eyes covered by fur, entrain to the daily light/dark cycle and adapt to seasonal changes due to an intact circadian timing system. The present study demonstrates that the Spalax retina contains a photoreceptor layer, an outer nuclear layer (ONL), an outer plexiform layer (OPL), an inner nuclear layer (INL), an inner plexiform layer (IPL), and a ganglion cell layer (GCL). By immunohistochemistry, the number of melanopsin (mRGCs) and non-melanopsin bearing retinal ganglion cells was analyzed in detail. Using the ganglion cell marker RNA-binding protein with multiple splicing (RBPMS) it was shown that the Spalax eye contains 890 +/- 62 RGCs. Of these, 87% (752 +/- 40) contain melanopsin (cell density 788 melanopsin RGCs/mm(2)). The remaining RGCs were shown to co-store Brn3a and calretinin. The melanopsin cells were located mainly in the GCL with projections forming two dendritic plexuses located in the inner part of the IPL and in the OPL. Few melanopsin dendrites were also found in the ONL. The Spalax retina is rich in rhodopsin and long/middle wave (L/M) cone opsin bearing photoreceptor cells. By using Ctbp2 as a marker for ribbon synapses, both rods and L/M cone ribbons containing pedicles in the OPL were found in close apposition with melanopsin dendrites in the outer plexus suggesting direct synaptic contact. A subset of cone bipolar cells and all photoreceptor cells contain recoverin while a subset of bipolar and amacrine cells contain calretinin. The calretinin expressing amacrine cells seemed to form synaptic contacts with rhodopsin containing photoreceptor cells in the OPL and contacts with melanopsin cell bodies and dendrites in the IPL. The study demonstrates the complex retinal circuitry used by the Spalax to detect light, and provides evidence for both melanopsin and non-melanopsin projecting pathways to the brain. PMID- 27375439 TI - Editorial: Auditory Efferent System: New Insights from Cortex to Cochlea. PMID- 27375440 TI - Intrinsic Hippocampal Excitability Changes of Opposite Signs and Different Origins in CA1 and CA3 Pyramidal Neurons Underlie Aging-Related Cognitive Deficits. AB - Aging-related cognitive deficits have been attributed to dysfunction of neurons due to failures at synaptic or intrinsic loci, or both. Given the importance of the hippocampus for successful encoding of memory and that the main output of the hippocampus is via the CA1 pyramidal neurons, much of the research has been focused on identifying the aging-related changes of these CA1 pyramidal neurons. We and others have discovered that the postburst afterhyperpolarization (AHP) following a train of action potentials is greatly enlarged in CA1 pyramidal neurons of aged animals. This enlarged postburst AHP is a significant factor in reducing the intrinsic excitability of these neurons, and thus limiting their activity in the neural network during learning. Based on these data, it has largely been thought that aging-related cognitive deficits are attributable to reduced activity of pyramidal neurons. However, recent in vivo and ex vivo studies provide compelling evidence that aging-related deficits could also be due to a converse change in CA3 pyramidal neurons, which show increased activity with aging. In this review, we will incorporate these recent findings and posit that an interdependent dynamic dysfunctional change occurs within the hippocampal network, largely due to altered intrinsic excitability in CA1 and CA3 hippocampal pyramidal neurons, which ultimately leads to the aging-related cognitive deficits. PMID- 27375441 TI - Periodic Visuotactile Stimulation Slowly Enhances the Rubber Hand Illusion in Individuals with High Autistic Traits. AB - In a rubber hand illusion (RHI) task, synchronous brush stroking of a rubber hand and a participant's hidden hand induces body ownership of the rubber hand. The effects of spatial distances and temporal lags on the RHI have been extensively examined; however, the effect of periodicity of the stimuli on illusory body ownership has not been examined. Meanwhile, the occurrence of RHI tends to be weak in individuals with autism-spectrum disorders (ASD) and high autistic traits. Preference for stimulus having regularity of tempo is generally observed in individuals with ASD, and thus, periodic stimulation might be more effective to elicit the body ownership illusion in individuals with high autistic traits. Hence, we investigated whether stimulus periodicity influenced RHI as well as its association with participant's autistic traits. Brush strokes were applied to a participant's own hand and the rubber hand periodically (2 s) or non-periodically (1-3 s), either synchronously or asynchronously. Two blocks were performed in each condition. We found that periodic stimulation enhanced the spatial updating of tactile sensation induced by RHI in the subsequent block in participants with high autistic traits, whereas both periodic and non-periodic stimulation strongly elicited RHI in blocks 1 and 2. These results indicate that the periodicity of stimulation has different effects based on an individual's autistic traits. Since individuals with ASD are known to sustain their focus on interoceptive sensations (heartbeats), a periodic stimulation that is potentially correlated with heartbeats might be effective to enhance the visuotactile integration during RHI in individuals with high autistic traits. PMID- 27375442 TI - Profound and Sexually Dimorphic Effects of Clinically-Relevant Low Dose Scatter Irradiation on the Brain and Behavior. AB - Irradiated cells can signal damage and distress to both close and distant neighbors that have not been directly exposed to the radiation (naive bystanders). While studies have shown that such bystander effects occur in the shielded brain of animals upon body irradiation, their mechanism remains unexplored. Observed effects may be caused by some blood-borne factors; however they may also be explained, at least in part, by very small direct doses received by the brain that result from scatter or leakage. In order to establish the roles of low doses of scatter irradiation in the brain response, we developed a new model for scatter irradiation analysis whereby one rat was irradiated directly at the liver and the second rat was placed adjacent to the first and received a scatter dose to its body and brain. This work focuses specifically on the response of the latter rat brain to the low scatter irradiation dose. Here, we provide the first experimental evidence that very low, clinically relevant doses of scatter irradiation alter gene expression, induce changes in dendritic morphology, and lead to behavioral deficits in exposed animals. The results showed that exposure to radiation doses as low as 0.115 cGy caused changes in gene expression and reduced spine density, dendritic complexity, and dendritic length in the prefrontal cortex tissues of females, but not males. In the hippocampus, radiation altered neuroanatomical organization in males, but not in females. Moreover, low dose radiation caused behavioral deficits in the exposed animals. This is the first study to show that low dose scatter irradiation influences the brain and behavior in a sex-specific way. PMID- 27375443 TI - Cohort Removal Induces Changes in Body Temperature, Pain Sensitivity, and Anxiety Like Behavior. AB - Mouse behavior is analyzed to elucidate the effects of various experimental manipulations, including gene mutation and drug administration. When the effect of a factor of interest is assessed, other factors, such as age, sex, temperature, apparatus, and housing, are controlled in experiments by matching, counterbalancing, and/or randomizing. One such factor that has not attracted much attention is the effect of sequential removal of animals from a common cage (cohort removal). Here we evaluated the effects of cohort removal on rectal temperature, pain sensitivity, and anxiety-like behavior by analyzing the combined data of a large number of C57BL/6J mice that we collected using a comprehensive behavioral test battery. Rectal temperature increased in a stepwise manner according to the position of sequential removal from the cage, consistent with previous reports. In the hot plate test, the mice that were removed first from the cage had a significantly longer latency to show the first paw response than the mice removed later. In the elevated plus maze, the mice removed first spent significantly less time on the open arms compared to the mice removed later. The results of the present study demonstrated that cohort removal induces changes in body temperature, pain sensitivity, and anxiety-like behavior in mice. Cohort removal also increased the plasma corticosterone concentration in mice. Thus, the ordinal position in the sequence of removal from the cage should be carefully counterbalanced between groups when the effect of experimental manipulations, including gene manipulation and drug administration, are examined using behavioral tests. PMID- 27375446 TI - Analysis of Individual Mouse Activity in Group Housed Animals of Different Inbred Strains using a Novel Automated Home Cage Analysis System. AB - Central nervous system disorders such as autism as well as the range of neurodegenerative diseases such as Huntington's disease are commonly investigated using genetically altered mouse models. The current system for characterizing these mice usually involves removing the animals from their home-cage environment and placing them into novel environments where they undergo a battery of tests measuring a range of behavioral and physical phenotypes. These tests are often only conducted for short periods of times in social isolation. However, human manifestations of such disorders are often characterized by multiple phenotypes, presented over long periods of time and leading to significant social impacts. Here, we have developed a system which will allow the automated monitoring of individual mice housed socially in the cage they are reared and housed in, within established social groups and over long periods of time. We demonstrate that the system accurately reports individual locomotor behavior within the group and that the measurements taken can provide unique insights into the effects of genetic background on individual and group behavior not previously recognized. PMID- 27375445 TI - Odor Experiences during Preimaginal Stages Cause Behavioral and Neural Plasticity in Adult Honeybees. AB - In eusocial insects, experiences acquired during the development have long-term consequences on mature behavior. In the honeybee that suffers profound changes associated with metamorphosis, the effect of odor experiences at larval instars on the subsequent physiological and behavioral response is still unclear. To address the impact of preimaginal experiences on the adult honeybee, colonies containing larvae were fed scented food. The effect of the preimaginal experiences with the food odor was assessed in learning performance, memory retention and generalization in 3-5- and 17-19 day-old bees, in the regulation of their expression of synaptic-related genes and in the perception and morphology of their antennae. Three-five day old bees that experienced 1-hexanol (1-HEX) as food scent responded more to the presentation of the odor during the 1-HEX conditioning than control bees (i.e., bees reared in colonies fed unscented food). Higher levels of proboscis extension response (PER) to 1-HEX in this group also extended to HEXA, the most perceptually similar odor to the experienced one that we tested. These results were not observed for the group tested at older ages. In the brain of young adults, larval experiences triggered similar levels of neurexins (NRXs) and neuroligins (Nlgs) expression, two proteins that have been involved in synaptic formation after associative learning. At the sensory periphery, the experience did not alter the number of the olfactory sensilla placoidea, but did reduce the electrical response of the antennae to the experienced and novel odor. Our study provides a new insight into the effects of preimaginal experiences in the honeybee and the mechanisms underlying olfactory plasticity at larval stage of holometabolous insects. PMID- 27375447 TI - Waddington, Dynamic Systems, and Epigenetics. AB - Waddington coined the term "epigenetic" to attempt to explain the complex, dynamic interactions between the developmental environment and the genome that led to the production of phenotype. Waddington's thoughts on the importance of both adaptability and canalization of phenotypic development are worth recalling as well, as they emphasize the available range for epigenetic action and the importance of environmental feedback (or lack thereof) in the development of complex traits. We suggest that a dynamic systems view fits well with Waddington's conception of epigenetics in the developmental context, as well as shedding light on the study of the molecular epigenetic effects of the environment on brain and behavior. Further, the dynamic systems view emphasizes the importance of the multi-directional interchange between the organism, the genome and various aspects of the environment to the ultimate phenotype. PMID- 27375444 TI - DYRK1A, a Dosage-Sensitive Gene Involved in Neurodevelopmental Disorders, Is a Target for Drug Development in Down Syndrome. AB - Down syndrome (DS) is one of the leading causes of intellectual disability, and patients with DS face various health issues, including learning and memory deficits, congenital heart disease, Alzheimer's disease (AD), leukemia, and cancer, leading to huge medical and social costs. Remarkable advances on DS research have been made in improving cognitive function in mouse models for future therapeutic approaches in patients. Among the different approaches, DYRK1A inhibitors have emerged as promising therapeutics to reduce DS cognitive deficits. DYRK1A is a dual-specificity kinase that is overexpressed in DS and plays a key role in neurogenesis, outgrowth of axons and dendrites, neuronal trafficking and aging. Its pivotal role in the DS phenotype makes it a prime target for the development of therapeutics. Recently, disruption of DYRK1A has been found in Autosomal Dominant Mental Retardation 7 (MRD7), resulting in severe mental deficiency. Recent advances in the development of kinase inhibitors are expected, in the near future, to remove DS from the list of incurable diseases, providing certain conditions such as drug dosage and correct timing for the optimum long-term treatment. In addition the exact molecular and cellular mechanisms that are targeted by the inhibition of DYRK1A are still to be discovered. PMID- 27375448 TI - A Proof of Concept Study of Function-Based Statistical Analysis of fNIRS Data: Syntax Comprehension in Children with Specific Language Impairment Compared to Typically-Developing Controls. AB - Functional near infrared spectroscopy (fNIRS) is a neuroimaging technology that enables investigators to indirectly monitor brain activity in vivo through relative changes in the concentration of oxygenated and deoxygenated hemoglobin. One of the key features of fNIRS is its superior temporal resolution, with dense measurements over very short periods of time (100 ms increments). Unfortunately, most statistical analysis approaches in the existing literature have not fully utilized the high temporal resolution of fNIRS. For example, many analysis procedures are based on linearity assumptions that only extract partial information, thereby neglecting the overall dynamic trends in fNIRS trajectories. The main goal of this article is to assess the ability of a functional data analysis (FDA) approach for detecting significant differences in hemodynamic responses recorded by fNIRS. Children with and without SLI wore two, 3 * 5 fNIRS caps situated over the bilateral parasylvian areas as they completed a language comprehension task. FDA was used to decompose the high dimensional hemodynamic curves into the mean function and a few eigenfunctions to represent the overall trend and variation structures over time. Compared to the most popular GLM, we did not assume any parametric structure and let the data speak for itself. This analysis identified significant differences between the case and control groups in the oxygenated hemodynamic mean trends in the bilateral inferior frontal and left inferior posterior parietal brain regions. We also detected significant group differences in the deoxygenated hemodynamic mean trends in the right inferior posterior parietal cortex and left temporal parietal junction. These findings, using dramatically different approaches, experimental designs, data sets, and foci, were consistent with several other reports, confirming group differences in the importance of these two areas for syntax comprehension. The proposed FDA was consistent with the temporal characteristics of fNIRS, thus providing an alternative methodology for fNIRS analyses. PMID- 27375449 TI - What Impact does An Angry Context have Upon Us? The Effect of Anger on Functional Connectivity of the Right Insula and Superior Temporal Gyri. AB - Being in a social world requires an understanding of other people that is co determined in its meaning by the situation at hand. Therefore, we investigated the underlying neural activation occurring when we encounter someone acting in angry or joyful situation. We hypothesized a dynamic interplay between the right insula, both involved in mapping visceral states associated with emotional experiences and autonomic control, and the bilateral superior temporal gyri (STG), part of the "social brain", when facing angry vs. joyful situations. Twenty participants underwent a functional magnetic resonance imaging (fMRI) scanning session while watching video clips of actors grasping objects in joyful and angry situations. The analyses of functional connectivity, psychophysiological interaction (PPI) and dynamic causal modeling (DCM), all revealed changes in functional connectivity associated with the angry situation. Indeed, the DCM model showed that the modulatory effect of anger increased the ipsilateral forward connection from the right insula to the right STG, while it suppressed the contralateral one. Our findings reveal a critical role played by the right insula when we are engaged in angry situations. In addition, they suggest that facing angry people modulates the effective connectivity between these two nodes associated, respectively, with autonomic responses and bodily movements and human-agent motion recognition. Taken together, these results add knowledge to the current understanding of hierarchical brain network for social cognition. PMID- 27375450 TI - Repeated, Intermittent Social Defeat across the Entire Juvenile Period Resulted in Behavioral, Physiological, Hormonal, Immunological, and Neurochemical Alterations in Young Adult Male Golden Hamsters. AB - The developing brain is vulnerable to social defeat during the juvenile period. As complements of human studies, animal models of social defeat provide a straightforward approach to investigating the functional and neurobiological consequences of social defeats. Taking advantage of agonist behavior and social defeat in male golden hamster, a set of 6 experiments was conducted to investigate the consequences at multiple levels in young adulthood resulting from repeated, intermittent social defeats or "social threats" across the entire juvenile period. Male hamsters at postnatal day 28 (P28) were randomly assigned to either the social defeat, "social threat", or arena control group, and they correspondingly received a series of nine social interaction trials (i.e., either social defeat, "social threat", or arena control conditions) from P33 to P66. At the behavioral level (Experiment 1), we found that repeated social defeats (but not "social threats") significantly impacted locomotor activity in the familiar context and social interaction in the familiar/unfamiliar social contexts. At the physiological and hormonal levels (Experiments 2 and 3), repeated social defeat significantly enhanced the cortisol and norepinephrine concentrations in blood. Enlargement of the spleen was also found in the social defeat and "social threat" groups. At the immunological level (Experiment 4), the social defeat group showed lower levels of pro-inflammatory cytokines in the hypothalamus and hippocampus but higher concentration of IL-6 in the striatum compared to the other two groups. At the neurochemical level (Experiment 5), the socially defeated hamsters mainly displayed reductions of dopamine, dopamine metabolites, and 5-HT levels in the striatum and decreased level of 5-HT in the hippocampus. In Experiment 6, an increase in the spine density of hippocampal CA1 pyramidal neurons was specifically observed in the "social threat" group. Collectively, our findings indicate that repeated, intermittent social defeats throughout entire adolescence in hamsters impact their adult responses at multiple levels. Our results also suggest that the "social threat" group may serve as an appropriate control. This study further suggest that the alterations of behavioral responses and neurobiological functions in the body and brain might provide potential markers to measure the negative consequences of chronic social defeats. PMID- 27375451 TI - Functional Magnetic Resonance Imaging Neurofeedback-guided Motor Imagery Training and Motor Training for Parkinson's Disease: Randomized Trial. AB - OBJECTIVE: Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback (NF) uses feedback of the patient's own brain activity to self regulate brain networks which in turn could lead to a change in behavior and clinical symptoms. The objective was to determine the effect of NF and motor training (MOT) alone on motor and non-motor functions in Parkinson's Disease (PD) in a 10-week small Phase I randomized controlled trial. METHODS: Thirty patients with Parkinson's disease (PD; Hoehn and Yahr I-III) and no significant comorbidity took part in the trial with random allocation to two groups. Group 1 (NF: 15 patients) received rt-fMRI-NF with MOT. Group 2 (MOT: 15 patients) received MOT alone. The primary outcome measure was the Movement Disorder Society Unified PD Rating Scale-Motor scale (MDS-UPDRS-MS), administered pre- and post intervention "off-medication". The secondary outcome measures were the "on medication" MDS-UPDRS, the PD Questionnaire-39, and quantitative motor assessments after 4 and 10 weeks. RESULTS: Patients in the NF group were able to upregulate activity in the supplementary motor area (SMA) by using motor imagery. They improved by an average of 4.5 points on the MDS-UPDRS-MS in the "off medication" state (95% confidence interval: -2.5 to -6.6), whereas the MOT group improved only by 1.9 points (95% confidence interval +3.2 to -6.8). The improvement in the intervention group meets the minimal clinically important difference which is also on par with other non-invasive therapies such as repetitive Transcranial Magnetic Stimulation (rTMS). However, the improvement did not differ significantly between the groups. No adverse events were reported in either group. INTERPRETATION: This Phase I study suggests that NF combined with MOT is safe and improves motor symptoms immediately after treatment, but larger trials are needed to explore its superiority over active control conditions. PMID- 27375452 TI - Repetitive Transcranial Direct Current Stimulation Induced Excitability Changes of Primary Visual Cortex and Visual Learning Effects-A Pilot Study. AB - Studies on noninvasive motor cortex stimulation and motor learning demonstrated cortical excitability as a marker for a learning effect. Transcranial direct current stimulation (tDCS) is a non-invasive tool to modulate cortical excitability. It is as yet unknown how tDCS-induced excitability changes and perceptual learning in visual cortex correlate. Our study aimed to examine the influence of tDCS on visual perceptual learning in healthy humans. Additionally, we measured excitability in primary visual cortex (V1). We hypothesized that anodal tDCS would improve and cathodal tDCS would have minor or no effects on visual learning. Anodal, cathodal or sham tDCS were applied over V1 in a randomized, double-blinded design over four consecutive days (n = 30). During 20 min of tDCS, subjects had to learn a visual orientation-discrimination task (ODT). Excitability parameters were measured by analyzing paired-stimulation behavior of visual-evoked potentials (ps-VEP) and by measuring phosphene thresholds (PTs) before and after the stimulation period of 4 days. Compared with sham-tDCS, anodal tDCS led to an improvement of visual discrimination learning (p < 0.003). We found reduced PTs and increased ps-VEP ratios indicating increased cortical excitability after anodal tDCS (PT: p = 0.002, ps-VEP: p = 0.003). Correlation analysis within the anodal tDCS group revealed no significant correlation between PTs and learning effect. For cathodal tDCS, no significant effects on learning or on excitability could be seen. Our results showed that anodal tDCS over V1 resulted in improved visual perceptual learning and increased cortical excitability. tDCS is a promising tool to alter V1 excitability and, hence, perceptual visual learning. PMID- 27375453 TI - Decoupling Actions from Consequences: Dorsal Hippocampal Lesions Facilitate Instrumental Performance, but Impair Behavioral Flexibility in Rats. AB - The present study is part of a series of experiments, where we analyze why and how damage of the rat's dorsal hippocampus (dHC) can enhance performance in a sequential reaction time task (SRTT). In this task, sequences of distinct visual stimulus presentations are food-rewarded in a fixed-ratio-13-schedule. Our previous study (Busse and Schwarting, 2016) had shown that rats with lesions of the dHC show substantially shorter session times and post-reinforcement pauses (PRPs) than controls, which allows for more practice when daily training is kept constant. Since sequential behavior is based on instrumental performance, a sequential benefit might be secondary to that. In order to test this hypothesis in the present study, we performed two experiments, where pseudorandom rather than sequential stimulus presentation was used in rats with excitotoxic dorsal hippocampal lesions. Again, we found enhanced performance in the lesion-group in terms of shorter session times and PRPs. During the sessions we found that the lesion-group spent less time with non-instrumental behavior (i.e., grooming, sniffing, and rearing) after prolonged instrumental training. Also, such rats showed moderate evidence for an extinction impairment under devalued food reward conditions and significant deficits in a response-outcome (R-O)-discrimination task in comparison to a control-group. These findings suggest that facilitatory effects on instrumental performance after dorsal hippocampal lesions may be primarily a result of complex behavioral changes, i.e., reductions of behavioral flexibility and/or alterations in motivation, which then result in enhanced instrumental learning. PMID- 27375454 TI - Making Decisions under Ambiguity: Judgment Bias Tasks for Assessing Emotional State in Animals. AB - Judgment bias tasks (JBTs) are considered as a family of promising tools in the assessment of emotional states of animals. JBTs provide a cognitive measure of optimism and/or pessimism by recording behavioral responses to ambiguous stimuli. For instance, a negative emotional state is expected to produce a negative or pessimistic judgment of an ambiguous stimulus, whereas a positive emotional state produces a positive or optimistic judgment of the same ambiguous stimulus. Measuring an animal's emotional state or mood is relevant in both animal welfare research and biomedical research. This is reflected in the increasing use of JBTs in both research areas. We discuss the different implementations of JBTs with animals, with a focus on their potential as an accurate measure of emotional state. JBTs have been successfully applied to a very broad range of species, using many different types of testing equipment and experimental protocols. However, further validation of this test is deemed necessary. For example, the often extensive training period required for successful judgment bias testing remains a possible factor confounding results. Also, the issue of ambiguous stimuli losing their ambiguity with repeated testing requires additional attention. Possible improvements are suggested to further develop the JBTs in both animal welfare and biomedical research. PMID- 27375455 TI - Finding the Beat: From Socially Coordinated Vocalizations in Songbirds to Rhythmic Entrainment in Humans. AB - Humans and oscine songbirds share the rare capacity for vocal learning. Songbirds have the ability to acquire songs and calls of various rhythms through imitation. In several species, birds can even coordinate the timing of their vocalizations with other individuals in duets that are synchronized with millisecond-accuracy. It is not known, however, if songbirds can perceive rhythms holistically nor if they are capable of spontaneous entrainment to complex rhythms, in a manner similar to humans. Here we review emerging evidence from studies of rhythm generation and vocal coordination across songbirds and humans. In particular, recently developed experimental methods have revealed neural mechanisms underlying the temporal structure of song and have allowed us to test birds' abilities to predict the timing of rhythmic social signals. Surprisingly, zebra finches can readily learn to anticipate the calls of a "vocal robot" partner and alter the timing of their answers to avoid jamming, even in reference to complex rhythmic patterns. This capacity resembles, to some extent, human predictive motor response to an external beat. In songbirds, this is driven, at least in part, by the forebrain song system, which controls song timing and is essential for vocal learning. Building upon previous evidence for spontaneous entrainment in human and non-human vocal learners, we propose a comparative framework for future studies aimed at identifying shared mechanism of rhythm production and perception across songbirds and humans. PMID- 27375456 TI - Bihemispheric-tDCS and Upper Limb Rehabilitation Improves Retention of Motor Function in Chronic Stroke: A Pilot Study. AB - BACKGROUND: Single sessions of bihemispheric transcranial direct-current stimulation (bihemispheric-tDCS) with concurrent rehabilitation improves motor function in stroke survivors, which outlasts the stimulation period. However few studies have investigated the behavioral and neurophysiological adaptations following a multi-session intervention of bihemispheric-tDCS concurrent with rehabilitation. OBJECTIVE: This pilot study explored the immediate and lasting effects of 3-weeks of bihemispheric-tDCS and upper limb (UL) rehabilitation on motor function and corticospinal plasticity in chronic stroke survivors. METHODS: Fifteen chronic stroke survivors underwent 3-weeks of UL rehabilitation with sham or real bihemispheric-tDCS. UL motor function was assessed via the Motor Assessment Scale (MAS), Tardieu Scale and grip strength. Corticospinal plasticity was indexed by motor evoked potentials (MEPs), cortical silent period (CSP) and short-interval intracortical inhibition (SICI) recorded from the paretic and non paretic ULs, using transcranial magnetic stimulation (TMS). Measures were taken at baseline, 48 h post and 3-weeks following (follow-up) the intervention. RESULTS: MAS improved following both real-tDCS (62%) and sham-tDCS (43%, P < 0.001), however at 3-weeks follow-up, the real-tDCS condition retained these newly regained motor skills to a greater degree than sham-tDCS (real-tDCS 64%, sham-tDCS 21%, P = 0.002). MEP amplitudes from the paretic UL increased for real tDCS (46%: P < 0.001) and were maintained at 3-weeks follow-up (38%: P = 0.03), whereas no changes were observed with sham-tDCS. No changes in MEPs from the non paretic nor SICI from the paretic UL were observed for either group. SICI from the non-paretic UL was greater at follow-up, for real-tDCS (27%: P = 0.04). CSP from the non-paretic UL increased by 33% following the intervention for real-tDCS compared with sham-tDCS (P = 0.04), which was maintained at 3-weeks follow-up (24%: P = 0.04). CONCLUSION: bihemispheric-tDCS improved retention of gains in motor function, which appears to be modulated through intracortical inhibitory pathways in the contralesional primary motor cortex (M1). The findings provide preliminary evidence for the benefits of bihemispheric-tDCS during rehabilitation. Larger clinical trials are warranted to examine long term benefits of bihemispheric-tDCS in a stroke affected population. PMID- 27375457 TI - Intra-Auditory Integration Improves Motor Performance and Synergy in an Accurate Multi-Finger Pressing Task. AB - Humans detect changes in the air pressure and understand the surroundings through the auditory system. The sound humans perceive is composed of two distinct physical properties, frequency and intensity. However, our knowledge is limited how the brain perceives and combines these two properties simultaneously (i.e., intra-auditory integration), especially in relation to motor behaviors. Here, we investigated the effect of intra-auditory integration between the frequency and intensity components of auditory feedback on motor outputs in a constant finger force production task. The hierarchical variability decomposition model previously developed was used to decompose motor performance into mathematically independent components each of which quantifies a distinct motor behavior such as consistency, repeatability, systematic error, within-trial synergy, or between trial synergy. We hypothesized that feedback on two components of sound as a function of motor performance (frequency and intensity) would improve motor performance and multi-finger synergy compared to feedback on just one component (frequency or intensity). Subjects were instructed to match the reference force of 18 N with the sum of all finger forces (virtual finger or VF force) while listening to auditory feedback of their accuracy. Three experimental conditions were used: (i) condition F, where frequency changed; (ii) condition I, where intensity changed; (iii) condition FI, where both frequency and intensity changed. Motor performance was enhanced for the FI conditions as compared to either the F or I condition alone. The enhancement of motor performance was achieved mainly by the improved consistency and repeatability. However, the systematic error remained unchanged across conditions. Within- and between-trial synergies were also improved for the FI condition as compared to either the F or I condition alone. However, variability of individual finger forces for the FI condition was not significantly decreased as compared to I condition alone. This result indicates an improvement in motor performance is consistent with Bayesian estimation, and changes in multi-finger interaction mostly result in the enhanced motor performance. These findings provide evidence that the central nervous system can take advantage of the intra-auditory integration in a statistically optimal (Bayesian) fashion to enhance motor performance by improving multi-finger synergy. PMID- 27375458 TI - Cortical Signal Analysis and Advances in Functional Near-Infrared Spectroscopy Signal: A Review. AB - Functional near-infrared spectroscopy (fNIRS) is a non-invasive neuroimaging modality that measures the concentration changes of oxy-hemoglobin (HbO) and de oxy hemoglobin (HbR) at the same time. It is an emerging cortical imaging modality with a good temporal resolution that is acceptable for brain-computer interface applications. Researchers have developed several methods in last two decades to extract the neuronal activation related waveform from the observed fNIRS time series. But still there is no standard method for analysis of fNIRS data. This article presents a brief review of existing methodologies to model and analyze the activation signal. The purpose of this review article is to give a general overview of variety of existing methodologies to extract useful information from measured fNIRS data including pre-processing steps, effects of differential path length factor (DPF), variations and attributes of hemodynamic response function (HRF), extraction of evoked response, removal of physiological noises, instrumentation, and environmental noises and resting/activation state functional connectivity. Finally, the challenges in the analysis of fNIRS signal are summarized. PMID- 27375459 TI - Theta Oscillation Reveals the Temporal Involvement of Different Attentional Networks in Contingent Reorienting. AB - In the visual world, rapidly reorienting to relevant objects outside the focus of attention is vital for survival. This ability from the interaction between goal directed and stimulus-driven attentional control is termed contingent reorienting. Neuroimaging studies have demonstrated activations of the ventral and dorsal attentional networks (DANs) which exhibit right hemisphere dominance, but the temporal dynamics of the attentional networks still remain unclear. The present study used event-related potential (ERP) to index the locus of spatial attention and Hilbert-Huang transform (HHT) to acquire the time-frequency information during contingent reorienting. The ERP results showed contingent reorienting induced significant N2pc on both hemispheres. In contrast, our time frequency analysis found further that, unlike the N2pc, theta oscillation during contingent reorienting differed between hemispheres and experimental sessions. The inter-trial coherence (ITC) of the theta oscillation demonstrated that the two sides of the attentional networks became phase-locked to contingent reorienting at different stages. The left attentional networks were associated with contingent reorienting in the first experimental session whereas the bilateral attentional networks play a more important role in this process in the subsequent session. This phase-locked information suggests a dynamic temporal evolution of the involvement of different attentional networks in contingent reorienting and a potential role of the left ventral network in the first session. PMID- 27375460 TI - The Brain from Within. AB - Functional magnetic resonance imaging (fMRI) provides a powerful way to visualize brain functions and observe brain activity in response to tasks or thoughts. It allows displaying brain damages that can be quantified and linked to neurobehavioral deficits. fMRI can potentially draw a new cartography of brain functional areas, allow us to understand aspects of brain function evolution or even breach the wall into cognition and consciousness. However, fMRI is not deprived of pitfalls, such as limitation in spatial resolution, poor reproducibility, different time scales of fMRI measurements and neuron action potentials, low statistical values. Thus, caution is needed in the assessment of fMRI results and conclusions. Additional diagnostic techniques based on MRI such as arterial spin labeling (ASL) and the measurement of diffusion tensor imaging (DTI) provide new tools to assess normal brain development or disruption of anatomical networks in diseases. A cutting edge of recent research uses fMRI techniques to establish a "map" of neural connections in the brain, or "connectome". It will help to develop a map of neural connections and thus understand the operation of the network. New applications combining fMRI and real time visualization of one's own brain activity (rtfMRI) could empower individuals to modify brain response and thus could enable researchers or institutions to intervene in the modification of an individual behavior. The latter in particular, as well as the concern about the confidentiality and storage of sensitive information or fMRI and lie detectors forensic use, raises new ethical questions. PMID- 27375461 TI - Vitality Forms Processing in the Insula during Action Observation: A Multivoxel Pattern Analysis. AB - Observing the style of an action done by others allows the observer to understand the cognitive state of the agent. This information has been defined by Stern "vitality forms". Previous experiments showed that the dorso-central insula is selectively active both during vitality form observation and execution. In the present study, we presented participants with videos showing hand actions performed with different velocities and asked them to judge either their vitality form (gentle, neutral, rude) or their velocity (slow, medium, fast). The aim of the present study was to assess, using multi-voxel pattern analysis, whether vitality forms and velocities of observed goal-directed actions are differentially processed in the insula, and more specifically whether action velocity is encoded per se or it is an element that triggers neural populations of the insula encoding the vitality form. The results showed that, consistently across subjects, in the dorso-central sector of the insula there were voxels selectively tuned to vitality forms, while voxel tuned to velocity were rare. These results indicate that the dorso-central insula, which previous data showed to be involved in the vitality form processing, contains voxels specific for the action style processing. PMID- 27375462 TI - Change in Mean Frequency of Resting-State Electroencephalography after Transcranial Direct Current Stimulation. AB - Transcranial direct current stimulation (tDCS) is proposed as a tool to investigate cognitive functioning in healthy people and as a treatment for various neuropathological disorders. However, the underlying cortical mechanisms remain poorly understood. We aim to investigate whether resting-state electroencephalography (EEG) can be used to monitor the effects of tDCS on cortical activity. To this end we tested whether the spectral content of ongoing EEG activity is significantly different after a single session of active tDCS compared to sham stimulation. Twenty participants were tested in a sham controlled, randomized, crossover design. Resting-state EEG was acquired before, during and after active tDCS to the left dorsolateral prefrontal cortex (15 min of 2 mA tDCS) and sham stimulation. Electrodes with a diameter of 3.14 cm(2) were used for EEG and tDCS. Partial least squares (PLS) analysis was used to examine differences in power spectral density (PSD) and the EEG mean frequency to quantify the slowing of EEG activity after stimulation. PLS revealed a significant increase in spectral power at frequencies below 15 Hz and a decrease at frequencies above 15 Hz after active tDCS (P = 0.001). The EEG mean frequency was significantly reduced after both active tDCS (P < 0.0005) and sham tDCS (P = 0.001), though the decrease in mean frequency was smaller after sham tDCS than after active tDCS (P = 0.073). Anodal tDCS of the left DLPFC using a high current density bi-frontal electrode montage resulted in general slowing of resting-state EEG. The similar findings observed following sham stimulation question whether the standard sham protocol is an appropriate control condition for tDCS. PMID- 27375463 TI - Understanding Neuronal Architecture in Obesity through Analysis of White Matter Connection Strength. AB - Despite the prevalence of obesity, our understanding of its neurobiological underpinnings is insufficient. Diffusion weighted imaging and calculation of white matter connection strength are methods to describe the architecture of anatomical white matter tracts. This study is aimed to characterize white matter architecture within taste-reward circuitry in a population of obese individuals. Obese (n = 18, age = 28.7 +/- 8.3 years) and healthy control (n = 24, age = 27.4 +/- 6.3 years) women underwent diffusion weighted imaging. Using probabilistic fiber tractography (FSL PROBTRACKX2 toolbox) we calculated connection strength within 138 anatomical white matter tracts. Obese women (OB) displayed lower and greater connectivity within taste-reward circuitry compared to controls (Wilks' lambda < 0.001; p < 0.001). Connectivity was lower in white matter tracts connecting insula, amygdala, prefrontal cortex (PFC), orbitofrontal cortex (OFC) and striatum. Connectivity was greater between the amygdala and anterior cingulate cortex (ACC). This study indicates that lower white matter connectivity within white matter tracts of insula-fronto-striatal taste-reward circuitry are associated with obesity as well as greater connectivity within white matter tracts connecting the amygdala and ACC. The specificity of regions suggests sensory integration and reward processing are key associations that are altered in and might contribute to obesity. PMID- 27375464 TI - EEG and Eye Tracking Demonstrate Vigilance Enhancement with Challenge Integration. AB - Maintaining vigilance is possibly the first requirement for surveillance tasks where personnel are faced with monotonous yet intensive monitoring tasks. Decrement in vigilance in such situations could result in dangerous consequences such as accidents, loss of life and system failure. In this paper, we investigate the possibility to enhance vigilance or sustained attention using "challenge integration," a strategy that integrates a primary task with challenging stimuli. A primary surveillance task (identifying an intruder in a simulated factory environment) and a challenge stimulus (periods of rain obscuring the surveillance scene) were employed to test the changes in vigilance levels. The effect of integrating challenging events (resulting from artificially simulated rain) into the task were compared to the initial monotonous phase. EEG and eye tracking data is collected and analyzed for n = 12 subjects. Frontal midline theta power and frontal theta to parietal alpha power ratio which are used as measures of engagement and attention allocation show an increase due to challenge integration (p < 0.05 in each case). Relative delta band power of EEG also shows statistically significant suppression on the frontoparietal and occipital cortices due to challenge integration (p < 0.05). Saccade amplitude, saccade velocity and blink rate obtained from eye tracking data exhibit statistically significant changes during the challenge phase of the experiment (p < 0.05 in each case). From the correlation analysis between the statistically significant measures of eye tracking and EEG, we infer that saccade amplitude and saccade velocity decrease with vigilance decrement along with frontal midline theta and frontal theta to parietal alpha ratio. Conversely, blink rate and relative delta power increase with vigilance decrement. However, these measures exhibit a reverse trend when challenge stimulus appears in the task suggesting vigilance enhancement. Moreover, the mean reaction time is lower for the challenge integrated phase (RTmean = 3.65 +/- 1.4s) compared to initial monotonous phase without challenge (RTmean = 4.6 +/- 2.7s). Our work shows that vigilance level, as assessed by response of these vital signs, is enhanced by challenge integration. PMID- 27375465 TI - Interpretations of Frequency Domain Analyses of Neural Entrainment: Periodicity, Fundamental Frequency, and Harmonics. AB - Brain activity can follow the rhythms of dynamic sensory stimuli, such as speech and music, a phenomenon called neural entrainment. It has been hypothesized that low-frequency neural entrainment in the neural delta and theta bands provides a potential mechanism to represent and integrate temporal information. Low frequency neural entrainment is often studied using periodically changing stimuli and is analyzed in the frequency domain using the Fourier analysis. The Fourier analysis decomposes a periodic signal into harmonically related sinusoids. However, it is not intuitive how these harmonically related components are related to the response waveform. Here, we explain the interpretation of response harmonics, with a special focus on very low-frequency neural entrainment near 1 Hz. It is illustrated why neural responses repeating at f Hz do not necessarily generate any neural response at f Hz in the Fourier spectrum. A strong neural response at f Hz indicates that the time scales of the neural response waveform within each cycle match the time scales of the stimulus rhythm. Therefore, neural entrainment at very low frequency implies not only that the neural response repeats at f Hz but also that each period of the neural response is a slow wave matching the time scale of a f Hz sinusoid. PMID- 27375466 TI - Distinct and Overlapping Brain Areas Engaged during Value-Based, Mathematical, and Emotional Decision Processing. AB - When comparing between the values of different choices, human beings can rely on either more cognitive processes, such as using mathematical computation, or more affective processes, such as using emotion. However, the neural correlates of how these two types of processes operate during value-based decision-making remain unclear. In this study, we investigated the extent to which neural regions engaged during value-based decision-making overlap with those engaged during mathematical and emotional processing in a within-subject manner. In a functional magnetic resonance imaging experiment, participants viewed stimuli that always consisted of numbers and emotional faces that depicted two choices. Across tasks, participants decided between the two choices based on the expected value of the numbers, a mathematical result of the numbers, or the emotional face stimuli. We found that all three tasks commonly involved various cortical areas including frontal, parietal, motor, somatosensory, and visual regions. Critically, the mathematical task shared common areas with the value but not emotion task in bilateral striatum. Although the emotion task overlapped with the value task in parietal, motor, and sensory areas, the mathematical task also evoked responses in other areas within these same cortical structures. Minimal areas were uniquely engaged for the value task apart from the other two tasks. The emotion task elicited a more expansive area of neural activity whereas value and mathematical task responses were in more focal regions. Whole-brain spatial correlation analysis showed that valuative processing engaged functional brain responses more similarly to mathematical processing than emotional processing. While decisions on expected value entail both mathematical and emotional processing regions, mathematical processes have a more prominent contribution particularly in subcortical processes. PMID- 27375467 TI - Attachment Representation Moderates the Influence of Emotional Context on Information Processing. AB - The induction of emotional states has repeatedly been shown to affect cognitive processing capacities. At a neurophysiological level, P3 amplitude responses that are associated with attention allocation have been found to be reduced to task relevant stimuli during emotional conditions as compared to neutral conditions suggesting a draining impact of emotion on cognitive resources. Attachment theory claims that how individuals regulate their emotions is guided by an internal working model (IWM) of attachment that has formed early in life. While securely attached individuals are capable of freely evaluating their emotions insecurely attached ones tend to either suppress or heighten the emotional experience in a regulatory effort. To explore how attachment quality moderates the impact of emotional contexts on information processing event-related potentials (ERPs) in 41 individuals were assessed. Subjects were instructed to detect neutral target letters within an oddball paradigm. Various images taken from the International Affective Picture System (IAPS) served as background pictures and represented negative, positive and neutral task-irrelevant contexts. Attachment representation was assessed using the Adult Attachment Interview (AAI) and individuals were assigned to one of three categories (secure, insecure dismissing, insecure-preoccupied). At a behavioral level, the study revealed that negative emotionally conditions were associated with the detection of less target stimuli in insecure-dismissing subjects. Accordingly, ERPs yielded reduced P3 amplitudes in insecure-dismissing subjects when given a negative emotional context. We interpret these findings in terms of less sufficient emotion regulation strategies in insecure-dismissing subjects at the cost of accurate behavioral performance. The study suggests that attachment representation differentially moderates the relationship between emotional contexts and information processing most evident in insecure-dismissing subjects. PMID- 27375468 TI - Decline of Neuropsychological Abilities in a Large Sample of Patients with Multiple Sclerosis: A Two-Year Longitudinal Study. AB - OBJECTIVE: In this longitudinal study, we monitored two large groups of multiple sclerosis (MS) patients and healthy controls (HC) for 2 years, with the aim of comparing their neuropsychological profile over time. METHOD: Three hundred and twenty-two patients with MS and 303 HC were administered the Brief Repeatable Battery of Neuropsychological tests (BRB-N); neuropsychiatric measures were also administered. Two follow-ups were scheduled at 1 and 2 years, respectively. RESULTS: A linear mixed model (LMM) with random intercept was run by considering participants' performance on each test of the BRB-N at the three assessment points (baseline and follow-ups) as the within-subjects variable, and group (patients and controls) as the between-subjects factor. The interaction term was statistically significant for the tests: Symbol Digit Modalities test (SDMT) (p = 0.044), Paced Auditory Serial Addition test (PASAT) (p = 0.011) and Word List Generation (WLG) (p < 0.001), whereas for the PASAT-3 approached statistical significance (p = 0.05). In addition, a LMM with random intercept was also run by identifying three groups (controls, relapsing-remitting course of MS (i.e. RR MS), and prog-MS). The interaction term was statistically significant for: PASAT 3 (p = 0.017), PASAT-2 (p = 0.0026), and WLG (p = 0.0022). CONCLUSIONS: Our results corroborate on a very large scale evidence that the abilities tapped by the tasks SDMT, PASAT and WLG are particularly sensitive to MS, and further extend this issue by showing that these abilities are likely to be more sensitive than others to the progression of the disease, as compared to HC. PMID- 27375469 TI - The Enhanced Musical Rhythmic Perception in Second Language Learners. AB - Previous research suggests that mastering languages with distinct rather than similar rhythmic properties enhances musical rhythmic perception. This study investigates whether learning a second language (L2) contributes to enhanced musical rhythmic perception in general, regardless of first and second languages rhythmic properties. Additionally, we investigated whether this perceptual enhancement could be alternatively explained by exposure to musical rhythmic complexity, such as the use of compound meter in Turkish music. Finally, it investigates if an enhancement of musical rhythmic perception could be observed among L2 learners whose first language relies heavily on pitch information, as is the case with tonal languages. Therefore, we tested Turkish, Dutch and Mandarin L2 learners of English and Turkish monolinguals on their musical rhythmic perception. Participants' phonological and working memory capacities, melodic aptitude, years of formal musical training and daily exposure to music were assessed to account for cultural and individual differences which could impact their rhythmic ability. Our results suggest that mastering a L2 rather than exposure to musical rhythmic complexity could explain individuals' enhanced musical rhythmic perception. An even stronger enhancement of musical rhythmic perception was observed for L2 learners whose first and second languages differ regarding their rhythmic properties, as enhanced performance of Turkish in comparison with Dutch L2 learners of English seem to suggest. Such a stronger enhancement of rhythmic perception seems to be found even among L2 learners whose first language relies heavily on pitch information, as the performance of Mandarin L2 learners of English indicates. Our findings provide further support for a cognitive transfer between the language and music domain. PMID- 27375470 TI - Model-Based Comparison of Deep Brain Stimulation Array Functionality with Varying Number of Radial Electrodes and Machine Learning Feature Sets. AB - Deep brain stimulation (DBS) leads with radially distributed electrodes have potential to improve clinical outcomes through more selective targeting of pathways and networks within the brain. However, increasing the number of electrodes on clinical DBS leads by replacing conventional cylindrical shell electrodes with radially distributed electrodes raises practical design and stimulation programming challenges. We used computational modeling to investigate: (1) how the number of radial electrodes impact the ability to steer, shift, and sculpt a region of neural activation (RoA), and (2) which RoA features are best used in combination with machine learning classifiers to predict programming settings to target a particular area near the lead. Stimulation configurations were modeled using 27 lead designs with one to nine radially distributed electrodes. The computational modeling framework consisted of a three dimensional finite element tissue conductance model in combination with a multi compartment biophysical axon model. For each lead design, two-dimensional threshold-dependent RoAs were calculated from the computational modeling results. The models showed more radial electrodes enabled finer resolution RoA steering; however, stimulation amplitude, and therefore spatial extent of the RoA, was limited by charge injection and charge storage capacity constraints due to the small electrode surface area for leads with more than four radially distributed electrodes. RoA shifting resolution was improved by the addition of radial electrodes when using uniform multi-cathode stimulation, but non-uniform multi cathode stimulation produced equivalent or better resolution shifting without increasing the number of radial electrodes. Robust machine learning classification of 15 monopolar stimulation configurations was achieved using as few as three geometric features describing a RoA. The results of this study indicate that, for a clinical-scale DBS lead, more than four radial electrodes minimally improved in the ability to steer, shift, and sculpt axonal activation around a DBS lead and a simple feature set consisting of the RoA center of mass and orientation enabled robust machine learning classification. These results provide important design constraints for future development of high-density DBS arrays. PMID- 27375471 TI - BluePyOpt: Leveraging Open Source Software and Cloud Infrastructure to Optimise Model Parameters in Neuroscience. AB - At many scales in neuroscience, appropriate mathematical models take the form of complex dynamical systems. Parameterizing such models to conform to the multitude of available experimental constraints is a global non-linear optimisation problem with a complex fitness landscape, requiring numerical techniques to find suitable approximate solutions. Stochastic optimisation approaches, such as evolutionary algorithms, have been shown to be effective, but often the setting up of such optimisations and the choice of a specific search algorithm and its parameters is non-trivial, requiring domain-specific expertise. Here we describe BluePyOpt, a Python package targeted at the broad neuroscience community to simplify this task. BluePyOpt is an extensible framework for data-driven model parameter optimisation that wraps and standardizes several existing open-source tools. It simplifies the task of creating and sharing these optimisations, and the associated techniques and knowledge. This is achieved by abstracting the optimisation and evaluation tasks into various reusable and flexible discrete elements according to established best-practices. Further, BluePyOpt provides methods for setting up both small- and large-scale optimisations on a variety of platforms, ranging from laptops to Linux clusters and cloud-based compute infrastructures. The versatility of the BluePyOpt framework is demonstrated by working through three representative neuroscience specific use cases. PMID- 27375472 TI - NeuroPigPen: A Scalable Toolkit for Processing Electrophysiological Signal Data in Neuroscience Applications Using Apache Pig. AB - The recent advances in neurological imaging and sensing technologies have led to rapid increase in the volume, rate of data generation, and variety of neuroscience data. This "neuroscience Big data" represents a significant opportunity for the biomedical research community to design experiments using data with greater timescale, large number of attributes, and statistically significant data size. The results from these new data-driven research techniques can advance our understanding of complex neurological disorders, help model long term effects of brain injuries, and provide new insights into dynamics of brain networks. However, many existing neuroinformatics data processing and analysis tools were not built to manage large volume of data, which makes it difficult for researchers to effectively leverage this available data to advance their research. We introduce a new toolkit called NeuroPigPen that was developed using Apache Hadoop and Pig data flow language to address the challenges posed by large scale electrophysiological signal data. NeuroPigPen is a modular toolkit that can process large volumes of electrophysiological signal data, such as Electroencephalogram (EEG), Electrocardiogram (ECG), and blood oxygen levels (SpO2), using a new distributed storage model called Cloudwave Signal Format (CSF) that supports easy partitioning and storage of signal data on commodity hardware. NeuroPigPen was developed with three design principles: (a) Scalability the ability to efficiently process increasing volumes of data; (b) Adaptability the toolkit can be deployed across different computing configurations; and (c) Ease of programming-the toolkit can be easily used to compose multi-step data processing pipelines using high-level programming constructs. The NeuroPigPen toolkit was evaluated using 750 GB of electrophysiological signal data over a variety of Hadoop cluster configurations ranging from 3 to 30 Data nodes. The evaluation results demonstrate that the toolkit is highly scalable and adaptable, which makes it suitable for use in neuroscience applications as a scalable data processing toolkit. As part of the ongoing extension of NeuroPigPen, we are developing new modules to support statistical functions to analyze signal data for brain connectivity research. In addition, the toolkit is being extended to allow integration with scientific workflow systems. NeuroPigPen is released under BSD license at: https://sites.google.com/a/case.edu/neuropigpen/. PMID- 27375473 TI - Underrepresentation of African-Americans in Alzheimer's Trials: A Call for Affirmative Action. PMID- 27375474 TI - Chronic Inflammation Links Cancer and Parkinson's Disease. AB - An increasing number of genetic studies suggest that the pathogenesis of Parkinson's disease (PD) and cancer share common genes, pathways, and mechanisms. Despite a disruption in a wide range of similar biological processes, the end result is very different: uncontrolled proliferation and early neurodegeneration. Thus, the links between the molecular mechanisms that cause PD and cancer remain to be elucidated. We propose that chronic inflammation in neurons and tumors contributes to a microenvironment that favors the accumulation of DNA mutations and facilitates disease formation. This article appraises the key role of microglia, establishes the genetic role of COX2 and CARD15 in PD and cancer, and discusses prevention and treatment with this new perspective in mind. We examine the evidence that chronic inflammation is an important link between cancer and PD. PMID- 27375475 TI - Role of Endolysosomes in Skeletal Muscle Pathology Observed in a Cholesterol-Fed Rabbit Model of Alzheimer's Disease. AB - Deficits in skeletal muscles contribute not only to the functional decline in people living with Alzheimer's disease (AD), but also to AD pathogenesis. We have shown that endolysosome dysfunction plays an important role in the development of AD pathological features in a cholesterol-fed rabbit model of AD. Interestingly we observed in skeletal muscle from the rabbit AD model increased deposition of Abeta, phosphorylated tau, and ubiquitin. Here, we tested the hypothesis that endolysosome dysfunction commonly occurs in skeletal muscle and brain in this rabbit model of AD. In skeletal muscle of rabbits fed a 2% cholesterol-enriched diet for 12 weeks we observed the presence of abnormally enlarged endolysosomes, in which were increased accumulations of free cholesterol and multiple AD marker proteins subject to misfolding and aggregation including Abeta, phosphorylated tau, and ubiquitin. Moreover, in skeletal muscle of rabbits fed the cholesterol enriched diet we observed decreased specific activities of three different lysosome enzymes. Our results suggest that elevated levels of plasma cholesterol can disturb endolysosome structure and function as well as promote the development of AD-like pathological features in skeletal muscle and that these organellar changes might contribute to the development of skeletal muscle deficits in AD. PMID- 27375476 TI - Editorial: Perception and Cognition: Interactions in the Aging Brain. PMID- 27375477 TI - Tendon Extracellular Matrix Alterations in Ullrich Congenital Muscular Dystrophy. AB - Collagen VI (COLVI) is a non-fibrillar collagen expressed in skeletal muscle and most connective tissues. Mutations in COLVI genes cause two major clinical forms, Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD). In addition to congenital muscle weakness, patients affected by COLVI myopathies show axial and proximal joint contractures and distal joint hypermobility, which suggest the involvement of the tendon function. We examined a peroneal tendon biopsy and tenocyte culture of a 15-year-old patient affected by UCMD with compound heterozygous COL6A2 mutations. In patient's tendon biopsy, we found striking morphological alterations of tendon fibrils, consisting in irregular profiles and reduced mean diameter. The organization of the pericellular matrix of tenocytes, the primary site of collagen fibril assembly, was severely affected, as determined by immunoelectron microscopy, which showed an abnormal accumulation of COLVI and altered distribution of collagen I (COLI) and fibronectin (FBN). In patient's tenocyte culture, COLVI web formation and cell surface association were severely impaired; large aggregates of COLVI, which matched with COLI labeling, were frequently detected in the extracellular matrix. In addition, metalloproteinase MMP-2, an extracellular matrix-regulating enzyme, was increased in the conditioned medium of patient's tenocytes, as determined by gelatin zymography and western blot. Altogether, these data indicate that COLVI deficiency may influence the organization of UCMD tendon matrix, resulting in dysfunctional fibrillogenesis. The alterations of tendon matrix may contribute to the complex pathogenesis of COLVI related myopathies. PMID- 27375478 TI - Older Candidates for Subthalamic Deep Brain Stimulation in Parkinson's Disease Have a Higher Incidence of Psychiatric Serious Adverse Events. AB - OBJECTIVE: To investigate the incidence of serious adverse events (SAE) of subthalamic deep brain stimulation (STN-DBS) in elderly patients with Parkinson's disease (PD). METHODS: We investigated a group of 26 patients with PD who underwent STN-DBS at mean age 63.2 +/- 3.3 years. The operated patients from the EARLYSTIM study (mean age 52.9 +/- 6.6) were used as a comparison group. Incidences of SAE were compared between these groups. RESULTS: A higher incidence of psychosis and hallucinations was found in these elderly patients compared to the younger patients in the EARLYSTIM study (p < 0.01). CONCLUSIONS: The higher incidence of STN-DBS-related psychiatric complications underscores the need for comprehensive psychiatric pre- and postoperative assessment in older DBS candidates. However, these psychiatric SAE were transient, and the benefits of DBS clearly outweighed its adverse effects. PMID- 27375479 TI - Six-Year Training Improves Everyday Memory in Healthy Older People. Randomized Controlled Trial. AB - PURPOSE OF THE STUDY: Everyday memory of older persons does not improve with intensive memory training programs. This study proposes a change in these programs based on a time-extended and massive intervention format. DESIGN AND METHODS: The sample of 1007 healthy older persons (mean age 71.85; SD = 5.12) was randomized into 2 groups. The experimental group followed an extended 6 years of training (192 sessions over 192 weeks) whereas the control group received an intensive training (3 sessions per week for a total of 32 sessions in 11 weeks). The program included cognitive and emotional content whose effects were assessed with the Rivermead Behavioral Memory Test (RBMT) and with the Mini-Mental State Examination (MMSE). Both groups were evaluated initially, after 32 sessions, and again after 6 years. RESULTS: The relative improvements measured with Blom's derivative showed that everyday memory and mental status of the experimental group were significantly better both in the short (Delta% 8.31 in RBMT and Delta% 1.51 in MMSE) and in the long term (Delta% 12.54 in RBMT and Delta% 2.56 in MMSE). For everyday memory and mental level, the overall gain estimate representing the mean difference in pre-post change between time-extended and intensive groups was 0.27 (95% CI: 0.13-0.40) and 0.54 (95% CI: 0.40-0.67), respectively. Time-extended programs have significantly improved everyday memory in contrast with the usual intensive programs whose effects decay with time. There are also significant increases in mental level scores while daily life functionality is preserved in all subjects who completed the training. IMPLICATIONS: These results suggest that it is possible to preserve everyday memory in the long term with continuous training and practice. Massive and time extended formats may contribute in the future to a paradigm shift in memory programs for healthy older people. PMID- 27375480 TI - Inhibition of Soluble Epoxide Hydrolase Limits Mitochondrial Damage and Preserves Function Following Ischemic Injury. AB - AIMS: Myocardial ischemia can result in marked mitochondrial damage leading to cardiac dysfunction, as such identifying novel mechanisms to limit mitochondrial injury is important. This study investigated the hypothesis that inhibiting soluble epoxide hydrolase (sEH), responsible for converting epoxyeicosatrienoic acids to dihydroxyeicosatrienoic acids protects mitochondrial from injury caused by myocardial infarction. METHODS: sEH null and WT littermate mice were subjected to surgical occlusion of the left anterior descending (LAD) artery or sham operation. A parallel group of WT mice received an sEH inhibitor, trans-4-[4-(3 adamantan-1-y1-ureido)-cyclohexyloxy]-benzoic acid (tAUCB; 10 mg/L) or vehicle in the drinking water 4 days prior and 7 days post-MI. Cardiac function was assessed by echocardiography prior- and 7-days post-surgery. Heart tissues were dissected into infarct, peri-, and non-infarct regions to assess ultrastructure by electron microscopy. Complexes I, II, IV, citrate synthase, PI3K activities, and mitochondrial respiration were assessed in non-infarct regions. Isolated working hearts were used to measure the rates of glucose and palmitate oxidation. RESULTS: Echocardiography revealed that tAUCB treatment or sEH deficiency significantly improved systolic and diastolic function post-MI compared to controls. Reduced infarct expansion and less adverse cardiac remodeling were observed in tAUCB-treated and sEH null groups. EM data demonstrated mitochondrial ultrastructure damage occurred in infarct and peri-infarct regions but not in non infarct regions. Inhibition of sEH resulted in significant improvements in mitochondrial respiration, ATP content, mitochondrial enzymatic activities and restored insulin sensitivity and PI3K activity. CONCLUSION: Inhibition or genetic deletion of sEH protects against long-term ischemia by preserving cardiac function and maintaining mitochondrial efficiency. PMID- 27375481 TI - Comparative Transcriptome Analysis Identifies CCDC80 as a Novel Gene Associated with Pulmonary Arterial Hypertension. AB - Pulmonary arterial hypertension (PAH) is a heterogeneous disorder associated with a progressive increase in pulmonary artery resistance and pressure. Although various therapies have been developed, the 5-year survival rate of PAH patients remains low. There is thus an important need to identify novel genes that are commonly dysregulated in PAH of various etiologies and could be used as biomarkers and/or therapeutic targets. In this study, we performed comparative transcriptome analysis of five mammalian PAH datasets downloaded from a public database. We identified 228 differentially expressed genes (DEGs) from a rat PAH model caused by inhibition of vascular endothelial growth factor receptor under hypoxic conditions, 379 DEGs from a mouse PAH model associated with systemic sclerosis, 850 DEGs from a mouse PAH model associated with schistosomiasis, 1598 DEGs from one cohort of human PAH patients, and 4260 DEGs from a second cohort of human PAH patients. Gene-by-gene comparison identified four genes that were differentially upregulated or downregulated in parallel in all five sets of DEGs. Expression of coiled-coil domain containing 80 (CCDC80) and anterior gradient two genes was significantly increased in the five datasets, whereas expression of SMAD family member six and granzyme A was significantly decreased. Weighted gene co-expression network analysis revealed a connection between CCDC80 and collagen type I alpha 1 (COL1A1) expression. To validate the function of CCDC80 in vivo, we knocked out ccdc80 in zebrafish using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system. In vivo imaging of zebrafish expressing a fluorescent protein in endothelial cells showed that ccdc80 deletion significantly increased the diameter of the ventral artery, a vessel supplying blood to the gills. We also demonstrated that expression of col1a1 and endothelin 1 mRNA was significantly decreased in the ccdc80-knockout zebrafish. Finally, we examined Ccdc80 immunoreactivity in a rat PAHmodel and found increased expression in the hypertrophied media and adventitia of the pre-acinar pulmonary arteries (PAs) and in the thickened intima, media, and adventitia of the obstructed intra acinar PAs. These results suggest that increased expression of CCDC80 may be involved in the pathogenesis of PAH, potentially by modulating the expression of endothelin-1 and COL1A1. PMID- 27375483 TI - The Urotensin II System and Carotid Atherosclerosis: A Role in Vascular Calcification. AB - BACKGROUND AND AIMS: The aims of the present study were to determine the expression of urotensin II (UII), urotensin-II related peptide (URP), and their receptor (UT) in stable and unstable carotid atherosclerosis, and determine the effects of UII on human aortic smooth muscle cell (SMCs) calcification. METHODS AND RESULTS: We examined UII, URP, and UT protein expression in 88 carotid endarterectomy specimens using immunohistochemistry. Expression of UII, URP, and UT was more evident in unstable compared to stable plaques (P < 0.05). Multivariate Spearman correlation analyses revealed significant positive correlations between UII, URP and UT overall staining and presence of calcification, severity of stenosis and inflammation (P < 0.05). Subjects undergoing carotid endarterectomy had significantly higher plasma UII levels, as assessed by ELISA, when compared with normolipidemic healthy control subjects (P < 0.05). Incubation of human aortic SMCs cultured in phosphate media with varying concentrations of UII resulted in a significant increase in calcium deposition and alkaline phosphatase activity. UII also significantly increased beta-catenin translocation and expression of ALPL, BMP2, ON, and SOX9 (P < 0.05). Incubation of cells with phosphate medium alone increased the expression of the pre-UT and mature UT (P < 0.01), and addition of UII had a synergistic effect on pre-UT protein expression (P < 0.001) compared to phosphate medium alone. CONCLUSIONS: Upregulation of UII, URP, and UT in unstable carotid endarterectomy plaques and plasma, and the stimulatory effect of UII on vascular smooth muscle cell calcification suggest that the UII system may play a role in the pathogenesis of vascular calcification and stability of atherosclerosis. PMID- 27375482 TI - Soft TCPTP Agonism-Novel Target to Rescue Airway Epithelial Integrity by Exogenous Spermidine. AB - A reparative approach of disrupted epithelium in obstructive airway diseases, namely asthma and chronic obstructive pulmonary disease (COPD), may afford protection and long-lasting results compared to conventional therapies, e.g., corticosteroids or immunosuppressant drugs. Here, we propose the polyamine spermidine as a novel therapeutic agent in airways diseases, based on a recently identified mode of action: T-cell protein tyrosine phosphatase (TCPTP) agonism. It may include and surpass single-inhibitors of stress and secondary growth factor pathway signaling, i.e., the new medicinal chemistry in lung diseases. Enhanced polyamine biosynthesis has been charged with aggravating prognosis by competing for L-arginine at detriment of nitric oxide (NO) synthesis with bronchoconstrictive effects. Although excess spermine, a higher polyamine, is harmful to airways physiology, spermidine can pivot the cell homeostasis during stress conditions by the activation of TCPTP. In fact, the dephosphorylating activity of TCPTP inhibits the signaling cascade that leads to the expression of genes involved in detachment and epithelial-to-mesenchymal transition (EMT), and increases the expression of adhesion and tight junction proteins, thereby enhancing the barrier functionality in inflammation-prone tissues. Moreover, a further beneficial effect of spermidine may derive from its ability to promote autophagy, possibly in a TCPTP-dependent way. Since doses of spermidine in the micromolar range are sufficient to activate TCPTP, low amounts of spermidine administered in sustained release modality may provide an optimal pharmacologic profile for the treatment of obstructive airway diseases. PMID- 27375484 TI - Pharmacokinetics of Oral and Inhaled Terbutaline after Exercise in Trained Men. AB - AIM: The aim of the study was to investigate pharmacokinetics of terbutaline after oral and inhaled administration in healthy trained male subjects in relation to doping control. METHODS: Twelve healthy well-trained young men (27 +/ 2 years; mean +/- SE) underwent two pharmacokinetic trials that compared 10 mg oral terbutaline with 4 mg inhaled dry powder terbutaline. During each trial, subjects performed 90 min of bike ergometer exercise at 65% of maximal oxygen consumption. Blood (0-4 h) and urine (0-24 h) samples were collected before and after administration of terbutaline. Samples were analyzed for concentrations of terbutaline by high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). RESULTS: Pharmacokinetics differed between the two routes of administration. Serum Cmax and area under the serum concentration-time curve (AUC) were lower after oral administration compared to inhalation (Cmax: 4.2 +/- 0.3 vs. 8.5 +/- 0.7 ng/ml, P <= 0.001; AUC: 422 +/- 22 vs. 1308 +/- 119 ng/ml * min). Urine concentrations (sum of the free drug and the glucuronide) were lower after oral administration compared to inhalation 2 h (1100 +/- 204 vs. 61 +/- 10 ng/ml, P <= 0.05) and 4 h (734 +/- 110 vs. 340 +/- 48 ng/ml, P <= 0.001) following administration, whereas concentrations were higher for oral administration than inhalation 12 h following administration (190 +/- 41 vs. 399 +/- 108 ng/ml, P <= 0.05). Urine excretion rate was lower after oral administration than inhalation the first 2 h following administration (P <= 0.001). Systemic bioavailability ratio between the two routes of administration was 3.8:1 (inhaled: oral; P <= 0.001). CONCLUSION: Given the higher systemic bioavailability of inhaled terbutaline compared to oral, our results indicate that it is difficult to differentiate allowed inhaled use of terbutaline from prohibited oral ingestion based on urine concentrations in doping control analysis. However given the potential performance enhancing effect of high dose terbutaline, it is essential to establish a limit on the WADA doping list. PMID- 27375487 TI - Erratum: Molecular features of interaction between VEGFA and anti-angiogenic drugs used in retinal diseases: a computational approach. AB - [This corrects the article on p. 248 in vol. 6, PMID: 26578958.]. PMID- 27375485 TI - Modulation of Autophagy by Sorafenib: Effects on Treatment Response. AB - The multikinase inhibitor sorafenib is, at present, the only drug approved for the treatment of hepatocellular carcinoma (HCC), one of the most lethal types of cancer worldwide. However, the increase in the number of sorafenib tumor resistant cells reduces efficiency. A better knowledge of the intracellular mechanism of the drug leading to reduced cell survival could help to improve the benefits of sorafenib therapy. Autophagy is a bulk cellular degradation process activated in a broad range of stress situations, which allows cells to degrade misfolded proteins or dysfunctional organelles. This cellular route can induce survival or death, depending on cell status and media signals. Sorafenib, alone or in combination with other drugs is able to induce autophagy, but cell response to the drug depends on the complex integrative crosstalk of different intracellular signals. In cancerous cells, autophagy can be regulated by different cellular pathways (Akt-related mammalian target of rapamycin (mTOR) inhibition, 5' AMP-activated protein kinase (AMPK) induction, dissociation of B cell lymphoma 2 (Bcl-2) family proteins from Beclin-1), or effects of some miRNAs. Inhibition of mTOR signaling by sorafenib and diminished interaction between Beclin-1 and myeloid cell leukemia 1 (Mcl-1) have been related to induction of autophagy in HCC. Furthermore, changes in some miRNAs, such as miR 30alpha, are able to modulate autophagy and modify sensitivity in sorafenib resistant cells. However, although AMPK phosphorylation by sorafenib seems to play a role in the antiproliferative action of the drug, it does not relate with modulation of autophagy. In this review, we present an updated overview of the effects of sorafenib on autophagy and its related activation pathways, analyzing in detail the involvement of autophagy on sorafenib sensitivity and resistance. PMID- 27375486 TI - Chronic Psychosocial Stress Impairs Bone Homeostasis: A Study in the Social Isolation Reared Rat. AB - Chronic psychosocial stress is a key player in the onset and aggravation of mental diseases, including psychosis. Although a strong association between this psychiatric condition and other medical co-morbidities has been recently demonstrated, few data on the link between psychosis and bone homeostasis are actually available. The aim of this study was to investigate whether chronic psychosocial stress induced by 4 or 7 weeks of social isolation in drug-naive male Wistar rats could alter bone homeostasis in terms of bone thickness, mineral density and content, as well as markers of bone formation and resorption (sclerostin, cathepsin K, and CTX-I). We found that bone mineral density was increased in rats exposed to 7 weeks of social isolation, while no differences were detected in bone mineral content and area. Moreover, 7 weeks of social isolation lead to increase of femur thickness with respect to controls, suggesting the development of a hyperostosis condition. Isolated rats showed no changes in sclerostin levels, a marker of bone formation, compared to grouped animals. Conversely, bone resorption markers were significantly altered after 7 weeks of social isolation in terms of decrease in cathepsin K and increase of CTX I. No alterations were found after 4 weeks of isolation rearing. Our observations suggest that chronic psychosocial stress might affect bone homeostasis, more likely independently from drug treatment. Thus, the social isolation model might help to identify possible new therapeutic targets to treat the burden of chronic psychosocial stress and to attempt alternative therapy choices. PMID- 27375488 TI - A Model of the Cardiorespiratory Response to Aerobic Exercise in Healthy and Heart Failure Conditions. AB - The physiological response to physical exercise is now recognized as an important tool which can aid the diagnosis and treatment of cardiovascular diseases. This is due to the fact that several mechanisms are needed to accommodate a higher cardiac output and a higher oxygen delivery to tissues. The aim of the present work is to provide a fully closed loop cardiorespiratory simulator reproducing the main physiological mechanisms which arise during aerobic exercise. The simulator also provides a representation of the impairments of these mechanisms in heart failure condition and their effect on limiting exercise capacity. The simulator consists of a cardiovascular model including the left and right heart, pulmonary and systemic circulations. This latter is split into exercising and non exercising regions and is controlled by the baroreflex and metabolic mechanisms. In addition, the simulator includes a respiratory model reproducing the gas exchange in lungs and tissues, the ventilation control and the effects of its mechanics on the cardiovascular system. The simulator was tested and compared to the data in the literature at three different workloads whilst cycling (25, 49 and 73 watts). The results show that the simulator is able to reproduce the response to exercise in terms of: heart rate (from 67 to 134 bpm), cardiac output (from 5.3 to 10.2 l/min), leg blood flow (from 0.7 to 3.0 l/min), peripheral resistance (from 0.9 to 0.5 mmHg/(cm(3)/s)), central arteriovenous oxygen difference (from 4.5 to 10.8 ml/dl) and ventilation (6.1-25.5 l/min). The simulator was further adapted to reproduce the main impairments observed in heart failure condition, such as reduced sensitivity of baroreflex and metabolic controls, lower perfusion to the exercising regions (from 0.6 to 1.4 l/min) and hyperventilation (from 9.2 to 40.2 l/min). The simulator we developed is a useful tool for the description of the basic physiological mechanisms operating during exercise. It can reproduce how these mechanisms interact and how their impairments could limit exercise performance in heart failure condition. The simulator can thus be used in the future as a test bench for different therapeutic strategies aimed at improving exercise performance in cardiopathic subjects. PMID- 27375489 TI - Medullary Endocannabinoids Contribute to the Differential Resting Baroreflex Sensitivity in Rats with Altered Brain Renin-Angiotensin System Expression. AB - CB1 cannabinoid receptors are expressed on vagal afferent fibers and neurons within the solitary tract nucleus (NTS), providing anatomical evidence for their role in arterial baroreflex modulation. To better understand the relationship between the brain renin-angiotensin system (RAS) and endocannabinoid expression within the NTS, we measured dorsal medullary endocannabinoid tissue content and the effects of CB1 receptor blockade at this brain site on cardiac baroreflex sensitivity (BRS) in ASrAOGEN rats with low glial angiotensinogen, normal Sprague Dawley rats and (mRen2)27 rats with upregulated brain RAS expression. Mass spectrometry revealed higher levels of the endocannabinoid 2-arachidonoylglycerol in (mRen2)27 compared to ASrAOGEN rats (2.70 +/- 0.28 vs. 1.17 +/- 0.09 ng/mg tissue; P < 0.01), while Sprague-Dawley rats had intermediate content (1.85 +/- 0.27 ng/mg tissue). Microinjection of the CB1receptor antagonist SR141716A (36 pmol) into the NTS did not change cardiac BRS in anesthetized Sprague-Dawley rats (1.04 +/- 0.05 ms/mmHg baseline vs. 1.17 +/- 0.11 ms/mmHg after 10 min). However, SR141716A in (mRen2)27 rats dose-dependently improved BRS in this strain: 0.36 pmol of SR141716A increased BRS from 0.43 +/- 0.03 to 0.71 +/- 0.04 ms/mmHg (P < 0.001), and 36 pmol of SR141716A increased BRS from 0.47 +/- 0.02 to 0.94 +/- 0.10 ms/mmHg (P < 0.01). In contrast, 0.36 pmol (1.50 +/- 0.12 vs. 0.86 +/- 0.08 ms/mmHg; P < 0.05) and 36 pmol (1.38 +/- 0.16 vs. 0.46 +/- 0.003 ms/mmHg; P < 0.01) of SR141716A significantly reduced BRS in ASrAOGEN rats. These observations reveal differential dose-related effects of the brain endocannabinoid system that influence cardiovagal BRS in animals with genetic alterations in the brain RAS. PMID- 27375490 TI - Effects of Kefir on the Cardiac Autonomic Tones and Baroreflex Sensitivity in Spontaneously Hypertensive Rats. AB - AIMS: It has been previously shown that the probiotic kefir (a symbiotic matrix containing acid bacteria and yeasts) attenuated the hypertension and the endothelial dysfunction in spontaneously hypertensive rats (SHR). In the present study, the effect of chronic administration of kefir on the cardiac autonomic control of heart rate (HR) and baroreflex sensitivity (BRS) in SHR was evaluated. METHODS: SHR were treated with kefir (0.3 mL/100 g body weight) for 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Cardiac autonomic vagal (VT) and sympathetic (ST) tones were estimated through the blockade of the cardiac muscarinic receptors (methylatropine) and the blockade of beta1-adrenoceptor (atenolol). The BRS was evaluated by the tachycardia and bradycardia responses to vasoactive drug-induced decreases and increases in arterial blood pressure (BP), respectively. Additionally, spontaneous BRS was estimated by autoregressive spectral analysis. RESULTS: Kefir-treated SHR exhibited significant attenuation of basal BP, HR, and cardiac hypertrophy compared to non-treated SHR (12, 13, and 21%, respectively). Cardiac VT and ST were significantly altered in the SHR (~40 and ~90 bpm) compared with Wistar rats (~120 and ~30 bpm) and were partially recovered in SHR-kefir (~90 and ~25 bpm). SHR exhibited an impaired bradycardic BRS (~50%) compared with Wistar rats, which was reduced to ~40% in the kefir-treated SHR and abolished by methylatropine in all groups. SHR also exhibited a significant impairment of the tachycardic BRS (~23%) compared with Wistar rats and this difference was reduced to 8% in the SHR kefir. Under the action of atenolol the residual reflex tachycardia was smaller in SHR than in Wistar rats and kefir attenuated this abnormality. Spectral analysis revealed increased low frequency components of BP (~3.5-fold) and pulse interval (~2-fold) compared with Wistar rats and these differences were reduced by kefir-treatment to ~1.6- and ~1.5-fold, respectively. Spectral analysis also showed an impairment of spontaneous BRS in SHR, but kefir-treatment caused only a tendency to reverse this result. CONCLUSIONS: The novelty of this study is that daily chronic consumption of a low dose of kefir reduced the impairment of the cardiac autonomic control of HR and of the impaired BRS in SHR. PMID- 27375491 TI - Matrix metalloproteinase-9 Gene-1562C>T Gene Polymorphism and Coronary Artery Disease in the Chinese Han Population: A Meta-Analysis of 5468 Subjects. AB - BACKGROUND: Multiple studies indicate that the matrix metalloproteinase-9 (MMP-9) 1562C>T gene polymorphism may be associated with an increased risk of coronary artery disease (CAD) in the Chinese Han population. However, a clear consensus has yet to be established. OBJECTIVE AND METHODS: A meta-analysis of 5468 subjects from 10 separate studies was performed to explore the possible relationship between the MMP-9-1562C>T gene polymorphism and CAD within the Chinese Han population. Pooled odds ratio (ORs) for the association and the corresponding 95% confidence intervals (CIs) were evaluated by a random or fixed effect model. RESULTS: Our analysis confirms the association between the MMP-9 1562C>T gene polymorphism and an increased risk of CAD within the Chinese Han population under allelic (OR: 1.60, 95% CI: 1.25-2.04, P = 0.0002), recessive (OR: 3.05, 95% CI: 1.67-5.56, P = 0.0003), dominant (OR: 2.23, 95% CI: 1.49-3.35, P = 0.0001), homozygous (OR: 3.41, 95% CI: 1.87-6.23, P < 0.0001), heterozygous (OR: 2.03, 95% CI: 1.40-2.93, P = 0.0002), and additive genetic models (OR: 1.78, 95% CI: 1.33-2.39, P < 0.0001). CONCLUSIONS: In the Chinese Han population, the MMP-9-1562C>T gene polymorphism is correlated with an increased risk of CAD. Therefore, Han Chinese carriers of the -1562T allele may be at an increased risk of CAD. PMID- 27375492 TI - Plasma Hypoxanthine-Guanine Phosphoribosyl Transferase Activity in Bottlenose Dolphins Contributes to Avoiding Accumulation of Non-recyclable Purines. AB - Marine mammals are exposed to ischemia/reperfusion and hypoxia/reoxygenation during diving. During oxygen deprivation, adenosine triphosphate (ATP) breakdown implies purine metabolite accumulation, which in humans is associated with pathological conditions. Purine recycling in seals increases in response to prolonged fasting and ischemia. Concentrations of metabolites and activities of key enzymes in purine metabolism were examined in plasma and red blood cells from bottlenose dolphins (Tursiops truncatus) and humans. Hypoxanthine and inosine monophosphate concentrations were higher in plasma from dolphins than humans. Plasma hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity in dolphins suggests an elevated purine recycling rate, and a mechanism for avoiding accumulation of non-recyclable purines (xanthine and uric acid). Red blood cell concentrations of hypoxanthine, adenosine diphosphate, ATP and guanosine triphosphate were lower in dolphins than in humans; adenosine monophosphate and nicotinamide adenine dinucleotide concentrations were higher in dolphins. HGPRT activity in red blood cells was higher in humans than in dolphins. The lower concentrations of purine catabolism and recycling by-products in plasma from dolphins could be beneficial in providing substrates for recovery of ATP depleted during diving or vigorous swimming. These results suggest that purine salvage in dolphins could be a mechanism for delivering nucleotide precursors to tissues with high ATP and guanosine triphosphate requirements. PMID- 27375493 TI - Greater Beta-Adrenergic Receptor Mediated Vasodilation in Women Using Oral Contraceptives. AB - BACKGROUND: beta-adrenergic receptors play an important role in mitigating the pressor effects of sympathetic nervous system activity in young women. Based on recent data showing oral contraceptive use in women abolishes the relationship between muscle sympathetic nervous system activity and blood pressure, we hypothesized forearm blood flow responses to a beta-adrenergic receptor agonist would be greater in young women currently using oral contraceptives (OC+, n = 13) when compared to those not using oral contraceptives (OC-, n = 10). METHODS: Women (18-35 years) were studied during the early follicular phase of the menstrual cycle (days 1-5) or placebo phase of oral contraceptive use. Forearm blood flow (FBF, Doppler ultrasound) and mean arterial blood pressure (MAP, brachial arterial catheter) were measured at baseline and during graded brachial artery infusion of the beta-adrenergic receptor agonist, Isoproterenol (ISO), as well as Acetylcholine (ACH, endothelium-dependent vasodilation) and Nitroprusside (NTP, endothelium-independent vasodilation). Forearm vascular conductance was calculated (FVC = FBF/MAP, ml/min/100 mmHg) and the rise in FVC from baseline during infusion quantified vasodilation (DeltaFVC = FVCinfusion - FVCbaseline). RESULTS: ISO increased FVC in both groups (p < 0.01) and ISO-mediated DeltaFVC was greater in OC+ compared to OC- (Main effect of group, p = 0.02). Expressing data as FVC and FBF resulted in similar conclusions. FVC responses to both ACH and NTP were also greater in OC+ compared to OC-. CONCLUSIONS: These data are the first to demonstrate greater beta-adrenergic receptor-mediated vasodilation in the forearm of women currently using oral contraceptives (placebo phase) when compared to those not using oral contraceptives (early follicular phase), and suggest oral contraceptive use influences neurovascular control. PMID- 27375494 TI - T Wave Amplitude Correction of QT Interval Variability for Improved Repolarization Lability Measurement. AB - OBJECTIVES: The inverse relationship between QT interval variability (QTV) and T wave amplitude potentially confounds QT variability assessment. We quantified the influence of the T wave amplitude on QTV in a comprehensive dataset and devised a correction formula. METHODS: Three ECG datasets of healthy subjects were analyzed to model the relationship between T wave amplitude and QTV. To derive a generally valid correction formula, linear regression analysis was used. The proposed correction formula was applied to patients enrolled in the Evaluation of Defibrillator in Non-Ischemic Cardiomyopathy Treatment Evaluation trial (DEFINITE) to assess the prognostic significance of QTV for all-cause mortality in patients with non-ischemic dilated cardiomyopathy. RESULTS: A strong inverse relationship between T wave amplitude and QTV was demonstrated, both in healthy subjects (R (2) = 0.68, p < 0.001) and DEFINITE patients (R (2) = 0.20, p < 0.001). Applying the T wave amplitude correction to QTV achieved 2.5-times better group discrimination between patients enrolled in the DEFINITE study and healthy subjects. Kaplan-Meier estimator analysis showed that T wave amplitude corrected QTVi is inversely related to survival (p < 0.01) and a significant predictor of all-cause mortality. CONCLUSION: We have proposed a simple correction formula for improved QTV assessment. Using this correction, predictive value of QTV for all cause mortality in patients with non-ischemic cardiomyopathy has been demonstrated. PMID- 27375496 TI - The Movement- and Load-Dependent Differences in the EMG Patterns of the Human Arm Muscles during Two-Joint Movements (A Preliminary Study). AB - Slow circular movements of the hand with a fixed wrist joint that were produced in a horizontal plane under visual guidance during conditions of action of the elastic load directed tangentially to the movement trajectory were studied. The positional dependencies of the averaged surface EMGs in the muscles of the elbow and shoulder joints were compared for four possible combinations in the directions of load and movements. The EMG intensities were largely correlated with the waves of the force moment computed for a corresponding joint in the framework of a simple geometrical model of the system: arm - experimental setup. At the same time, in some cases the averaged EMGs exit from the segments of the trajectory restricted by the force moment singular points (FMSPs), in which the moments exhibited altered signs. The EMG activities display clear differences for the eccentric and concentric zones of contraction that are separated by the joint angle singular points (JASPs), which present extreme at the joint angle traces. We assumed that the modeled patterns of FMSPs and JASPs may be applied for an analysis of the synergic interaction between the motor commands arriving at different muscles in arbitrary two-joint movements. PMID- 27375495 TI - The Combined Effects of Ethylene and MeJA on Metabolic Profiling of Phenolic Compounds in Catharanthus roseus Revealed by Metabolomics Analysis. AB - Phenolic compounds belong to a class of secondary metabolites and are implicated in a wide range of responsive mechanisms in plants triggered by both biotic and abiotic elicitors. In this study, we approached the combinational effects of ethylene and MeJA (methyl jasmonate) on phenolic compounds profiles and gene expressions in the medicinal plant Catharanthus roseus. In virtue of a widely non targeted metabolomics method, we identified a total of 34 kinds of phenolic compounds in the leaves, composed by 7 C6C1-, 11 C6C3-, and 16 C6C3C6 compounds. In addition, 7 kinds of intermediates critical for the biosynthesis of phenolic compounds and alkaloids were identified and discussed with phenolic metabolism. The combinational actions of ethylene and MeJA effectively promoted the total phenolic compounds, especially the C6C1 compounds (such as salicylic acid, benzoic acid) and C6C3 ones (such as cinnamic acid, sinapic acid). In contrast, the C6C3C6 compounds displayed a notably inhibitory trend in this case. Subsequently, the gene-to-metabolite networks were drawn up by searching for correlations between the expression profiles of 5 gene tags and the accumulation profiles of 41 metabolite peaks. Generally, we provide an insight into the controlling mode of ethylene-MeJA combination on phenolic metabolism in C. roseus leaves. PMID- 27375497 TI - Enhancement of Glucose Metabolism via PGC-1alpha Participates in the Cardioprotection of Chronic Intermittent Hypobaric Hypoxia. AB - BACKGROUND AND AIMS: Previous studies demonstrated that energy metabolism disturbance impairs cardiac function and chronic intermittent hypobaric hypoxia (CIHH) protects heart against ischemia/reperfusion injury. The present study aimed to test the hypothesis that CIHH protects the heart against ischemia/reperfusion (I/R) injury via improvement of cardiac glucose metabolism. METHODS: Male Sprague-Dawley rats received CIHH treatment simulating 5000-m altitude for 28 days, 6 h per day in a hypobaric chamber or no treatment (control). Body weight, fasting blood glucose, blood lipid and glucose tolerance were measured. The left ventricular function of isolated hearts was evaluated during 30 min of ischemia and 60 min of reperfusion using Langendorff method. The mRNA and protein expression involved in cardiac energy metabolism was determined using quantitative PCR and Western blot techniques. RESULTS: 1. There was no difference of body weight, fast blood glucose, blood lipid and glucose tolerance between control and CIHH rats under baseline condition (p > 0.05). 2. The recovery of left ventricular function after I/R was improved significantly in CIHH rats compared to control rats (p < 0.05). 3. The expression of cardiac GLUT4 and PGC-1alpha was increased but PDK4 gene expression was decreased by CIHH treatment at both mRNA and protein level. Also p-AMPK/AMPK ratio was increased in CIHH rats (p < 0.05). CONCLUSION: CIHH ameliorates I/R injury through improving cardiac glucose metabolism via upregulation of GLUT4, p-AMPK, and PGC-1alpha expressions, but downregulation of cardiacPDK4 expression. PMID- 27375498 TI - Chronic Kidney Disease As a Potential Indication for Renal Denervation. AB - Renal denervation is being used as a blood pressure lowering therapy for patients with apparent treatment resistant hypertension. However, this population does not represent a distinct disease condition in which benefit is predictable. In fact, the wide range in effectiveness of renal denervation could be a consequence of this heterogeneous pathogenesis of hypertension. Since renal denervation aims at disrupting sympathetic nerves surrounding the renal arteries, it seems obvious to focus on patients with increased afferent and/or efferent renal sympathetic nerve activity. In this review will be argued, from both a pathophysiological and a clinical point of view, that chronic kidney disease is particularly suited to renal denervation. PMID- 27375499 TI - Muscle MCT4 Content Is Correlated with the Lactate Removal Ability during Recovery Following All-Out Supramaximal Exercise in Highly-Trained Rowers. AB - The purpose of this study was to test if the lactate exchange (gamma1) and removal (gamma2) abilities during recovery following short all-out supramaximal exercise correlate with the muscle content of MCT1 and MCT4, the two isoforms of the monocarboxylate transporters family involved in lactate and H(+) co-transport in skeletal muscle. Eighteen lightweight rowers completed a 3-min all-out exercise on rowing ergometer. Blood lactate samples were collected during the subsequent passive recovery to assess an individual blood lactate curve (IBLC). IBLC were fitted to the bi-exponential time function: La(t) = [La](0) + A1(1 - [Formula: see text]) + A2(1 - [Formula: see text]) where [La](0) is the blood lactate concentration at exercise completion and the velocity constants gamma1 and gamma2 denote the lactate exchange and removal abilities, respectively. An application of the bi-compartmental model of lactate distribution space allowed estimation of the lactate removal rate at exercise completion [LRR(0)]. Biopsy of the right vastus lateralis was taken at rest to measure muscle MCT1 and MCT4 content. Fiber type distribution, activity of key enzymes and capillary density (CD) were also assessed. gamma1 was correlated with [La](0) (r = -0.54, P < 0.05) but not with MCT1, MCT4 or CD. gamma2 and LRR(0) were correlated with MCT4 (r = 0.63, P < 0.01 and r = 0.73, P < 0.001, respectively) but not with MCT1 or cytochrome c oxidase activity. These findings suggest that the lactate exchange ability is highly dependent on the milieu so that the importance of the muscle MCT1 and MCT4 content in gamma1 was hidden in the present study. Our results also suggest that during recovery following all-out supramaximal exercise in well trained rowers, MCT4 might play a significant role in the distribution and delivery of lactate for its subsequent removal. PMID- 27375500 TI - Therapeutic Use of Exercising in Hypoxia: Promises and Limitations. PMID- 27375501 TI - Editorial: New Translational Insights on Metabolic Syndrome: Obesity, Hypertension, Diabetes and Beyond. PMID- 27375502 TI - Transition for Adolescents with Autism Spectrum Disorder: South African Parent and Professional Perspectives. AB - Adolescents with autism and their families experience a significant increase in the number of challenges encountered when leaving the structure of the formal education system. The purpose of this study was to gain an understanding of the factors parents and professionals regard as important in preparing for transition of adolescents with autism spectrum disorder (ASD) to adulthood, vocational, and residential arrangements. Semistructured interviews were conducted with 14 participants (i.e., 7 parents and 7 professionals) who were involved with adolescents with ASD in Johannesburg, South Africa. The findings revealed that there was a need for advocacy on behalf of learners with ASD transitioning into adult working and living environments. The responses of the participants highlighted needs for curriculum transformation from basic literacy skills to development and teaching of functional self-help and daily living skills. The results also indicated lack of planning and the absence of service facilities for adolescents with autism post-school. There was a general feeling of fear and uncertainty when the participants thought about transition of adolescents with autism and their future. However, there was also a sense of hope and optimism. Transition of adolescents with autism into adulthood is a challenging and stressful time for parents and professionals involved in trying to prepare them. With appropriate attention and support structures, individuals with autism can attain a reasonable quality of life, including residential, employment, and social opportunities. PMID- 27375503 TI - Comorbidities, Social Impact, and Quality of Life in Tourette Syndrome. AB - Tourette syndrome (TS) is more than having motor and vocal tics, and this review will examine the varied comorbidities as well as the social impact and quality of life (QoL) in individuals with TS. The relationship between any individual and his/her environment is complex, and this is further exaggerated in the case of a person with TS. For example, tics may play a significant role in shaping the person's experiences, perceptions, and interactions with the environment. Furthermore, associated clinical features, comorbidities, and coexisting psychopathologies may compound or alter this relationship. In this regard, the common comorbidities include attention-deficit hyperactivity disorder and disruptive behaviors, obsessive compulsive disorder, and autism spectrum disorder, and coexistent problems include anxiety, depression, and low self esteem, which can all lead to poorer psychosocial functioning and QoL. Thus, the symptoms of TS and the associated comorbid conditions may interact to result in a vicious cycle or a downward spiraling of negative experiences and poor QoL. The stigma and social maladjustment in TS and the social exclusion, bullying, and discrimination are considered to be caused in large part by misperceptions of the disorder by teachers, peers, and the wider community. Improved community and professional awareness about TS and related comorbidities and other psychopathologies as well as the provision of multidisciplinary services to meet the complex needs of this clinical population are critical. Future research to inform the risk and resilience factors for successful long-term outcomes is also warranted. PMID- 27375504 TI - The Limited Impact of Exposure Duration on Holistic Word Processing. AB - The current study explored the impact of stimuli exposure duration on holistic word processing measured by the complete composite paradigm (CPc paradigm). The participants were asked to match the cued target parts of two characters which were presented for either a long (600 ms) or a short duration (170 ms). They were also tested by two popular versions of the CPc paradigm: the "early-fixed" task where the attention cue was visible from the beginning of each trial at a fixed position, and the "delayed-random" task where the cue showed up after the study character at random locations. The holistic word effect, as indexed by the alignment * congruency interaction, was identified in both tasks and was unaffected by the stimuli duration in both tasks. Meanwhile, the "delayed-random" task did not bring about larger holistic word effect than the "early-fixed" task. These results suggest the exposure duration (from around 150 to 600 ms) has a limited impact on the holistic word effect, and have methodological implications for experiment designs in this field. PMID- 27375506 TI - The Influence of the Pinyin and Zhuyin Writing Systems on the Acquisition of Mandarin Word Forms by Native English Speakers. AB - The role of written input in second language (L2) phonological and lexical acquisition has received increased attention in recent years. Here we investigated the influence of two factors that may moderate the influence of orthography on L2 word form learning: (i) whether the writing system is shared by the native language and the L2, and (ii) if the writing system is shared, whether the relevant grapheme-phoneme correspondences are also shared. The acquisition of Mandarin via the Pinyin and Zhuyin writing systems provides an ecologically valid opportunity to explore these factors. We first asked whether there is a difference in native English speakers' ability to learn Pinyin and Zhuyin grapheme-phoneme correspondences. In Experiment 1, native English speakers assigned to either Pinyin or Zhuyin groups were exposed to Mandarin words belonging to one of two conditions: in the "congruent" condition, the Pinyin forms are possible English spellings for the auditory words (e.g., < nai> for [nai]); in the "incongruent" condition, the Pinyin forms involve a familiar grapheme representing a novel phoneme (e.g., < xiu> for [ciou]). At test, participants were asked to indicate whether auditory and written forms matched; in the crucial trials, the written forms from training (e.g., < xiu>) were paired with possible English pronunciations of the Pinyin written forms (e.g., [ziou]). Experiment 2 was identical to Experiment 1 except that participants additionally saw pictures depicting word meanings during the exposure phase, and at test were asked to match auditory forms with the pictures. In both experiments the Zhuyin group outperformed the Pinyin group due to the Pinyin group's difficulty with "incongruent" items. A third experiment confirmed that the groups did not differ in their ability to perceptually distinguish the relevant Mandarin consonants (e.g., [c]) from the foils (e.g., [z]), suggesting that the findings of Experiments 1 and 2 can be attributed to the effects of orthographic input. We thus conclude that despite the familiarity of Pinyin graphemes to native English speakers, the need to suppress native language grapheme-phoneme correspondences in favor of new ones can lead to less target-like knowledge of newly learned words' forms than does learning Zhuyin's entirely novel graphemes. PMID- 27375505 TI - Deficits in the Mimicry of Facial Expressions in Parkinson's Disease. AB - BACKGROUND: Humans spontaneously mimic the facial expressions of others, facilitating social interaction. This mimicking behavior may be impaired in individuals with Parkinson's disease, for whom the loss of facial movements is a clinical feature. OBJECTIVE: To assess the presence of facial mimicry in patients with Parkinson's disease. METHOD: Twenty-seven non-depressed patients with idiopathic Parkinson's disease and 28 age-matched controls had their facial muscles recorded with electromyography while they observed presentations of calm, happy, sad, angry, and fearful emotions. RESULTS: Patients exhibited reduced amplitude and delayed onset in the zygomaticus major muscle region (smiling response) following happy presentations (patients M = 0.02, 95% confidence interval [CI] -0.15 to 0.18, controls M = 0.26, CI 0.14 to 0.37, ANOVA, effect size [ES] = 0.18, p < 0.001). Although patients exhibited activation of the corrugator supercilii and medial frontalis (frowning response) following sad and fearful presentations, the frontalis response to sad presentations was attenuated relative to controls (patients M = 0.05, CI -0.08 to 0.18, controls M = 0.21, CI 0.09 to 0.34, ANOVA, ES = 0.07, p = 0.017). The amplitude of patients' zygomaticus activity in response to positive emotions was found to be negatively correlated with response times for ratings of emotional identification, suggesting a motor-behavioral link (r = -0.45, p = 0.02, two-tailed). CONCLUSIONS: Patients showed decreased mimicry overall, mimicking other peoples' frowns to some extent, but presenting with profoundly weakened and delayed smiles. These findings open a new avenue of inquiry into the "masked face" syndrome of PD. PMID- 27375507 TI - Decisions at the Brink: Locomotor Experience Affects Infants' Use of Social Information on an Adjustable Drop-off. AB - How do infants decide what to do at the brink of a precipice? Infants could use two sources of information to guide their actions: perceptual information generated by their own exploratory activity and social information offered by their caregivers. The current study investigated the role of locomotor experience in using social information-both encouragement and discouragement-for descending drop-offs. Mothers of 30 infants (experienced 12-month-old crawlers, novice 12 month-old walkers, and experienced 18-month-old walkers) encouraged and discouraged descent on a gradation of drop-offs (safe "steps" and risky "cliffs"). Novice walkers descended more frequently than experienced crawlers and walkers and fell while attempting to walk over impossibly high cliffs. All infants showed evidence of integrating perceptual and social information, but locomotor experience affected infants' use of social messages, especially on risky drop-offs. Experienced crawlers and walkers selectively deferred to social information when perceptual information is ambiguous. In contrast, novice walkers took mothers' advice inconsistently and only at extreme drop-offs. PMID- 27375508 TI - Shared and Unique Risk Factors Underlying Mathematical Disability and Reading and Spelling Disability. AB - High comorbidity rates have been reported between mathematical learning disabilities (MD) and reading and spelling disabilities (RSD). Research has identified skills related to math, such as number sense (NS) and visuospatial working memory (visuospatial WM), as well as to literacy, such as phonological awareness (PA), rapid automatized naming (RAN) and verbal short-term memory (Verbal STM). In order to explain the high comorbidity rates between MD and RSD, 7-11-year-old children were assessed on a range of cognitive abilities related to literacy (PA, RAN, Verbal STM) and mathematical ability (visuospatial WM, NS). The group of children consisted of typically developing (TD) children (n = 32), children with MD (n = 26), children with RSD (n = 29), and combined MD and RSD (n = 43). It was hypothesized that, in line with the multiple deficit view on learning disorders, at least one unique predictor for both MD and RSD and a possible shared cognitive risk factor would be found to account for the comorbidity between the symptom dimensions literacy and math. Secondly, our hypotheses were that (a) a probabilistic multi-factorial risk factor model would provide a better fit to the data than a deterministic single risk factor model and (b) that a shared risk factor model would provide a better fit than the specific multi-factorial model. All our hypotheses were confirmed. NS and visuospatial WM were identified as unique cognitive predictors for MD, whereas PA and RAN were both associated with RSD. Also, a shared risk factor model with PA as a cognitive predictor for both RSD and MD fitted the data best, indicating that MD and RSD might co-occur due to a shared underlying deficit in phonological processing. Possible explanations are discussed in the context of sample selection and composition. This study shows that different cognitive factors play a role in mathematics and literacy, and that a phonological processing deficit might play a role in the occurrence of MD and RSD. PMID- 27375509 TI - Infants Prefer Female Body Phenotypes; Infant Girls Prefer They Have an Hourglass Shape. AB - Adolescents and adults show preferences for male and female body shapes consistent with evolutionary theories of reproductive fitness and mate selection. However, when these preferences for females with narrow waists (i.e., 0.7 waist to-hip ratio) and men with broad shoulders (i.e., mesomorphic body shape) emerge during the lifespan is largely unknown. To address this knowledge gap, eye movements were tracked in 146 infants (3-18 months of age) during computer presentation of three-dimensional human figures varying in body features thought relevant for reproductive success (e.g., secondary sex characteristics, waist-to hip ratio). When presented with pairs of figures differing in apparent sex, male and female infants looked significantly longer at the female figure compared to the male figure, a new finding that extends previous research showing preferences for female faces in infancy. When presented with same-sex figures differing in characteristics associated with mate value, male and female infants looked longer at a low mate value male (i.e., an endomorphic body type) compared to a high mate value male (i.e., a mesomorphic body type), a finding that replicates the results of previous research. In addition, the novel use of high and low mate value female figures showed a sex difference in visual attention, such that female infants looked longer at the high mate value female figure compared to the low mate female figure whereas male infants showed the opposite pattern of results. In sum, these findings suggest that infants generally do not possess preferences for adult-defined attractive male body shapes. However, infant girls' greater attention to a female figure with an adult-preferred waist-to-hip ratio raises the possibility that evolved preferences for 0.7 waist-to-hip ratio influence girls' later preference for toys representing females with an hourglass shape, perhaps supporting elaboration of adult social behaviors that enhance reproductive success (e.g., cooperative breeding). PMID- 27375510 TI - Mindfulness-Oriented Meditation for Primary School Children: Effects on Attention and Psychological Well-Being. AB - Mindfulness-based interventions are increasingly being used as methods to promote psychological well-being of clinical and non-clinical adult populations. Much less is known, however, on the feasibility of these forms of mental training on healthy primary school students. Here, we tested the effects of a mindfulness meditation training on a group of 16 healthy children within 7-8 years of age from an Italian primary school. An active control condition focused on emotion awareness was employed on a group of 15 age-matched healthy children from the same school. Both programs were delivered by the same instructors three times per week, for 8 total weeks. The same main teacher of the two classes did not participate in the trainings but she completed questionnaires aimed at giving comprehensive pre-post training evaluations of behavior, social, emotion, and attention regulation skills in the children. A children's self-report measure of mood and depressive symptoms was also used. From the teacher's reports we found a specific positive effect of the mindfulness-meditation training in reducing attention problems and also positive effects of both trainings in reducing children's internalizing problems. However, subjectively, no child in either group reported less depressive symptoms after the trainings. The findings were interpreted as suggestive of a positive effect of mindfulness-meditation on several children's psychological well-being dimensions and were also discussed in light of the discrepancy between teacher and children's reports. More generally, the results were held to speak in favor of the effectiveness of mindfulness-based interventions for healthy primary school children. PMID- 27375511 TI - Impact of Player Injuries on Teams' Mental States, and Subsequent Performances, at the Rugby World Cup 2015. PMID- 27375512 TI - Studying Different Tasks of Implicit Learning across Multiple Test Sessions Conducted on the Web. AB - Implicit learning is usually studied through individual performance on a single task, with the most common tasks being the Serial Reaction Time (SRT) task, the Dynamic System Control (DSC) task, and Artificial Grammar Learning (AGL). Few attempts have been made to compare performance across different implicit learning tasks within the same study. The current study was designed to explore the relationship between performance on the DSC Sugar factory task and the Alternating Serial Reaction Time (ASRT) task. We also addressed another limitation of traditional implicit learning experiments, namely that implicit learning is usually studied in laboratory settings over a restricted time span lasting for less than an hour. In everyday situations, implicit learning is assumed to involve a gradual accumulation of knowledge across several learning episodes over a longer time span. One way to increase the ecological validity of implicit learning experiments could be to present the learning material repeatedly across shorter test sessions. This can most easily be done by using a web-based setup in which participants can access the material from home. We therefore created an online web-based system for measuring implicit learning that could be administered in either single or multiple sessions. Participants (n = 66) were assigned to either a single session or a multiple session condition. Learning occurred on both tasks, and awareness measures suggested that acquired knowledge was not fully conscious on either of the tasks. Learning and the degree of conscious awareness of the learned regularities were compared across conditions and tasks. On the DSC task, performance was not affected by whether learning had taken place in one or over multiple sessions. On the ASRT task, RT improvement across blocks was larger in the multiple-session condition. Learning in the two tasks was not related. PMID- 27375513 TI - The 2D:4D-Ratio and Neuroticism Revisited: Empirical Evidence from Germany and China. AB - The 2D:4D-Ratio, as an indirect measure of the fetal testosterone to estradiol ratio, is potentially very important for understanding and explaining different personality traits. It was the aim of the present study to replicate the findings from Fink et al. (2004) about the relation between individual differences in 2D:4D-Ratios and the Five Factor Model in different cultural groups. Therefore a sample of n = 78 Chinese and n = 370 German participants was recruited. Every participant provided hand scans of both hands, from which 2D:4D-Ratios were computed. Moreover, all participants filled in the NEO Five Factor Inventory (NEO FFI). Significant sex differences were found for ratios of both hands in the expected direction, with females showing higher ratios than males. With respect to links between personality and the digit ratio, a positive association was observed between 2D:4D-Ratio and Neuroticism in females, as shown in the earlier study. These findings were observed in both female subsamples from China and Germany, as well as in the full sample of participants. But in contrast to the results for the whole and the German female sample, where 2D:4D-Ratio of both hands were related to Neuroticism, in the Chinese female sample only left hand 2D:4D-Ratio was significantly and positively related to Neuroticism. There were no significant correlations found in any of the male samples. Thus, prenatal exposure to sex steroids appears to influence the personality factor Neuroticism in females specifically. This finding potentially has implications for mental health, as Neuroticism has been shown to be a risk factor for various forms of psychopathology. PMID- 27375514 TI - The Effect of Implicit-Explicit Followership Congruence on Benevolent Leadership: Evidence from Chinese Family Firms. AB - Benevolent leadership, a traditional Chinese leadership style generated under the influence of Confucianism, has been under growing discussion since its proposal. However, existing research has focused mainly on the consequences of benevolent leadership, and research probing into its antecedents is scarce. To fill such research gap, the current study aims to explore the effect of the congruence between implicit positive followership prototype (PFP) and explicit positive followership trait (PFT) on benevolent leadership. Polynomial regression combined with the response surface methodology was used to test the hypotheses herein. The results, based on a sample of 241 leader-follower dyads from four Chinese family firms, indicated the following: (1) benevolent leadership is higher when leader PFP is congruent with follower PFT than when they are incongruent; (2) in cases of congruence, benevolent leadership is higher when leader PFP and follower PFT are both high rather than low; (3) in the case of incongruence, there is no significant difference for the level of benevolent leadership in two scenarios: "low leader PFP - high follower PFT" and "high leader PFP - low follower PFT". PMID- 27375515 TI - Music As a Sacred Cue? Effects of Religious Music on Moral Behavior. AB - Religion can have an important influence in moral decision-making, and religious reminders may deter people from unethical behavior. Previous research indicated that religious contexts may increase prosocial behavior and reduce cheating. However, the perceptual-behavioral link between religious contexts and decision making lacks thorough scientific understanding. This study adds to the current literature by testing the effects of purely audial religious symbols (instrumental music) on moral behavior across three different sites: Mauritius, the Czech Republic, and the USA. Participants were exposed to one of three kinds of auditory stimuli (religious, secular, or white noise), and subsequently were given a chance to dishonestly report on solved mathematical equations in order to increase their monetary reward. The results showed cross-cultural differences in the effects of religious music on moral behavior, as well as a significant interaction between condition and religiosity across all sites, suggesting that religious participants were more influenced by the auditory religious stimuli than non-religious participants. We propose that religious music can function as a subtle cue associated with moral standards via cultural socialization and ritual participation. Such associative learning can charge music with specific meanings and create sacred cues that influence normative behavior. Our findings provide preliminary support for this view, which we hope further research will investigate more closely. PMID- 27375516 TI - Addiction: From Context-Induced Hedonia to Appetite, Based on Transition of Micro behaviors in Morphine Abstinent Tree Shrews. AB - Drug addiction is viewed as a maladaptive memory induced by contextual cues even in the abstinent state. However, the variations of hedonia and appetite induced by the context during the abstinence have been neglected. To distinguish the representative behaviors between hedonia and appetite, micro-behaviors in abstinent animal such as psycho-activity and drug seeking behaviors were observed in morphine conditioned place preference (CPP). To confirm the different effects of reward between drug and natural reward, a palatable food CPP paradigm was compared in current work. After a 10-day training in CPP with morphine or food, the preference was tested on day 1, 14, 28, and the changes of micro-behaviors were analyzed further. Our data showed that tree shrews treated with morphine performed more jumps on day 1 and more visits to saline paired side on day 28, which indicated a featured behavioral transition from psycho-activity to seeking behavior during drug abstinence. Meanwhile, food-conditioned animals only displayed obvious seeking behaviors in the three tests. The results suggest that the variations of micro-behaviors could imply such a transition from hedonic response to appetitive behaviors during morphine abstinence, which provided a potential behavioral basis for further neural mechanism studies. PMID- 27375518 TI - Joint-Angle Coordination Patterns Ensure Stabilization of a Body-Plus-Tool System in Point-to-Point Movements with a Rod. AB - When performing a goal-directed action with a tool, it is generally assumed that the point of control of the action system is displaced from the hand to the tool, implying that body and tool function as one system. Studies of how actions with tools are performed have been limited to studying either end-effector kinematics or joint-angle coordination patterns. Because joint-angle coordination patterns affect end-effector kinematics, the current study examined them together, with the aim of revealing how body and tool function as one system. Seated participants made point-to-point movements with their index finger, and with rods of 10, 20, and 30 cm attached to their index finger. Start point and target were presented on a table in front of them, and in half of the conditions a participant displacement compensated for rod length. Results revealed that the kinematics of the rod's tip showed higher peak velocity, longer deceleration time, and more curvature with longer rods. End-effector movements were more curved in the horizontal plane when participants were not displaced. Joint-angle trajectories were similar across rod lengths when participants were displaced, whereas more extreme joint-angles were used with longer rods when participants were not displaced. Furthermore, in every condition the end-effector was stabilized to a similar extent; both variability in joint-angle coordination patterns that affected end-effector position and variability that did not affect end-effector position increased in a similar way vis-a-vis rod length. Moreover, the increase was higher in those conditions, in which participants were not displaced. This suggests that during tool use, body and tool are united in a single system so as to stabilize the end-effector kinematics in a similar way that is independent of tool length. In addition, the properties of the actual trajectory of the end-effector, as well as the actual joint-angles used, depend on the length of the tool and the specifics of the task. PMID- 27375517 TI - Measuring the Performance of Attention Networks with the Dalhousie Computerized Attention Battery (DalCAB): Methodology and Reliability in Healthy Adults. AB - Attention is an important, multifaceted cognitive domain that has been linked to three distinct, yet interacting, networks: alerting, orienting, and executive control. The measurement of attention and deficits of attention within these networks is critical to the assessment of many neurological and psychiatric conditions in both research and clinical settings. The Dalhousie Computerized Attention Battery (DalCAB) was created to assess attentional functions related to the three attention networks using a range of tasks including: simple reaction time, go/no-go, choice reaction time, dual task, flanker, item and location working memory, and visual search. The current study provides preliminary normative data, test-retest reliability (intraclass correlations) and practice effects in DalCAB performance 24-h after baseline for healthy young adults (n = 96, 18-31 years). Performance on the DalCAB tasks demonstrated Good to Very Good test-retest reliability for mean reaction time, while accuracy and difference measures (e.g., switch costs, interference effects, and working memory load effects) were most reliable for tasks that require more extensive cognitive processing (e.g., choice reaction time, flanker, dual task, and conjunction search). Practice effects were common and pronounced at the 24-h interval. In addition, performance related to specific within-task parameters of the DalCAB sub-tests provides preliminary support for future formal assessment of the convergent validity of our interpretation of the DalCAB as a potential clinical and research assessment tool for measuring aspects of attention related to the alerting, orienting, and executive control networks. PMID- 27375519 TI - A New Conceptualization of Human Visual Sensory-Memory. AB - Memory is an essential component of cognition and disorders of memory have significant individual and societal costs. The Atkinson-Shiffrin "modal model" forms the foundation of our understanding of human memory. It consists of three stores: Sensory Memory (SM), whose visual component is called iconic memory, Short-Term Memory (STM; also called working memory, WM), and Long-Term Memory (LTM). Since its inception, shortcomings of all three components of the modal model have been identified. While the theories of STM and LTM underwent significant modifications to address these shortcomings, models of the iconic memory remained largely unchanged: A high capacity but rapidly decaying store whose contents are encoded in retinotopic coordinates, i.e., according to how the stimulus is projected on the retina. The fundamental shortcoming of iconic memory models is that, because contents are encoded in retinotopic coordinates, the iconic memory cannot hold any useful information under normal viewing conditions when objects or the subject are in motion. Hence, half-century after its formulation, it remains an unresolved problem whether and how the first stage of the modal model serves any useful function and how subsequent stages of the modal model receive inputs from the environment. Here, we propose a new conceptualization of human visual sensory memory by introducing an additional component whose reference-frame consists of motion-grouping based coordinates rather than retinotopic coordinates. We review data supporting this new model and discuss how it offers solutions to the paradoxes of the traditional model of sensory memory. PMID- 27375520 TI - Aversive Learning and Trait Aggression Influence Retaliatory Behavior. AB - In two experiments (n = 35, n = 34), we used a modified fear-conditioning paradigm to investigate the role of aversive learning in retaliatory behavior in social context. Participants first completed an initial aversive learning phase in which the pairing of a neutral conditioned stimulus (CS; i.e., neutral face) with a naturally aversive unconditioned stimulus (US; electric shock) was learned. Then they were given an opportunity to interact (i.e., administer 0-2 shocks) with the same faces again, during a Test phase. In Experiment 2, we used the same paradigm with the addition of online trial-by-trial ratings (e.g., US expectancy and anger) to examine the role of aversive learning, anger, and the learned expectancy of receiving punishment more closely. Our results indicate that learned aversions influenced future retaliation in a social context. In both experiments, participants showed largest skin conductance responses (SCRs) to the faces paired with one or two shocks, demonstrating successful aversive learning. Importantly, participants administered more shocks to the faces paired with the most number of shocks when the opportunity was given during test. Also, our results revealed that aggressive traits (Buss and Perry Aggression scale) were associated with retaliation only toward CSs associated with aversive experiences. These two experiments show that aggressive traits, when paired with aversive learning experiences enhance the likelihood to act anti-socially toward others. PMID- 27375521 TI - Combined Cognitive Training vs. Memory Strategy Training in Healthy Older Adults. AB - As mnemonic utilization deficit in older adults associates with age-related decline in executive function, we hypothesized that memory strategy training combined with executive function training might induce larger training effect in memory and broader training effects in non-memory outcomes than pure memory training. The present study compared the effects of combined cognitive training (executive function training plus memory strategy training) to pure memory strategy training. Forty healthy older adults were randomly assigned to a combined cognitive training group or a memory strategy training group. A control group receiving no training was also included. Combined cognitive training group received 16 sessions of training (eight sessions of executive function training followed by eight sessions of memory strategy training). Memory training group received 16 sessions of memory strategy training. The results partly supported our hypothesis in that indeed improved performance on executive function was only found in combined training group, whereas memory performance increased less in combined training compared to memory strategy group. Results suggest that combined cognitive training may be less efficient than pure memory training in memory outcomes, though the influences from insufficient training time and less closeness between trained executive function and working memory could not be excluded; however it has broader training effects in non-memory outcomes. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, identifier ChiCTR-OON-16007793. PMID- 27375522 TI - Should Touch Screen Tablets Be Used to Improve Educational Outcomes in Primary School Children in Developing Countries? PMID- 27375524 TI - Exercising for the Pleasure and for the Pain of It: The Implications of Different Forms of Hedonistic Thinking in Theories of Physical Activity Behavior. PMID- 27375523 TI - Challenges in Internet Addiction Disorder: Is a Diagnosis Feasible or Not? AB - An important international discussion began because of some pioneer studies carried out by Young (a) on the internet addiction disorder (IAD). In the fifth and most recent version of the Diagnostic, and Statistical Manual of Mental Disorders (DSM) there is no mention of this disorder and among researchers there are basically two opposite positions. Those who are in favor of a specific diagnosis and those who are claiming the importance of specific criteria characterizing this behavior and the precise role it has in the patient's life. The aim of the present paper is to answer the question whether it is possible or not to formulate diagnoses of internet-related disorders. We revised literature on the history of diagnostic criteria, on neurocognitive evidence, on the topic debate and on IAD instrumental measures. We found that the disorder was not univocally defined and that the construct was somehow too broad and generic to be explicative for a diagnosis. Indeed, the models are borrowed from other addiction pathologies and they are often formulated before the development of internet as intended in current society. In conclusion, we think we need a more innovative, integrated and comprehensive model for an IAD diagnosis. PMID- 27375526 TI - Interpersonal Harmony and Conflict for Chinese People: A Yin-Yang Perspective. AB - This article provides an overview on a series of original studies conducted by the author. The aim here is to present the ideas that the author reconstructed, based on the dialectics of harmonization, regarding harmony and conflict embodied in traditional Chinese thought, and to describe how a formal psychological theory/model on interpersonal harmony and conflict was developed based on the Yin Yang perspective. The paper also details how essential theories on interpersonal harmony and conflict were constructed under this formal model by conducting a qualitative study involving in-depth interviews with 30 adults. Psychological research in Western society has, intriguingly, long been focused more on interpersonal conflict than on interpersonal harmony. By contrast, the author's work started from the viewpoint of a materialist conception of history and dialectics of harmonization in order to reinterpret traditional Chinese thought. Next, a "dynamic model of interpersonal harmony and conflict" was developed, as a formal psychological theory, based on the real-virtual notions in the Yin-Yang perspective. Under this model, interpersonal harmony and conflict can be classified into genuine versus superficial harmony and authentic versus virtual focus conflict, and implicit/hidden conflict is regarded as superficial harmony. Subsequently, the author conducted a series of quantitative studies on interpersonal harmony and conflict within parent-child, supervisor-subordinate, and friend-friend relationships in order to verify the construct validity and the predictive validity of the dynamic model of interpersonal harmony and conflict. The claim presented herein is that Chinese traditional thought and the psychological theory/model based on the Yin-Yang perspective can be combined. Accordingly, by combining qualitative and quantitative empirical research, the relative substantial theory can be developed and the concepts can be validated. Thus, this work represents the realization of a series of modern Chinese indigenous psychological research studies rooted in traditional cultural thought and the Yin-Yang perspective. The work also mirrors the current conflict management research that has incorporated the Chinese notion of harmony and adopted the Yin-Yang perspective on culture. PMID- 27375525 TI - Salience and Attention in Surprisal-Based Accounts of Language Processing. AB - The notion of salience has been singled out as the explanatory factor for a diverse range of linguistic phenomena. In particular, perceptual salience (e.g., visual salience of objects in the world, acoustic prominence of linguistic sounds) and semantic-pragmatic salience (e.g., prominence of recently mentioned or topical referents) have been shown to influence language comprehension and production. A different line of research has sought to account for behavioral correlates of cognitive load during comprehension as well as for certain patterns in language usage using information-theoretic notions, such as surprisal. Surprisal and salience both affect language processing at different levels, but the relationship between the two has not been adequately elucidated, and the question of whether salience can be reduced to surprisal / predictability is still open. Our review identifies two main challenges in addressing this question: terminological inconsistency and lack of integration between high and low levels of representations in salience-based accounts and surprisal-based accounts. We capitalize upon work in visual cognition in order to orient ourselves in surveying the different facets of the notion of salience in linguistics and their relation with models of surprisal. We find that work on salience highlights aspects of linguistic communication that models of surprisal tend to overlook, namely the role of attention and relevance to current goals, and we argue that the Predictive Coding framework provides a unified view which can account for the role played by attention and predictability at different levels of processing and which can clarify the interplay between low and high levels of processes and between predictability-driven expectation and attention driven focus. PMID- 27375527 TI - A Perspective on Consumers 3.0: They Are Not Better Decision-Makers than Previous Generations. AB - This perspective article builds upon the theory of local thinking in interpretation and prediction of consumer behavior in a contemporary world of information overload. It is shown that even informed and socially and environmentally responsible consumers (consumers 3.0) exhibit selective recall, limited attention, and bounded search in the perception and interpretation of price and quality of purchases. Their decisions fall into local cognitive frames, which specifically focus attention only on a narrow structure and content of the choice. The cognitive frames can be established by recent or regular purchases, but also extreme or primary purchase experiences. The article includes a short conceptual review of car, food, clothing, insurance, drugs, paintings, and other product purchases showing that the local cognitive frames often lead to bad bargains across various sectors. The article presents several suggestions for future research. PMID- 27375528 TI - Anxiolytic Treatment Impairs Helping Behavior in Rats. AB - Despite decades of research with humans, the biological mechanisms that motivate an individual to help others remain poorly understood. In order to investigate the roots of pro-sociality in mammals, we established the helping behavior test, a paradigm in which rats are faced with a conspecific trapped in a restrainer that can only be opened from the outside. Over the course of repeated test sessions, rats exposed to a trapped cagemate learn to open the door to the restrainer, thereby helping the trapped rat to escape (Ben-Ami Bartal et al., 2011). The discovery of this natural behavior provides a unique opportunity to probe the motivation of rodent helping behavior, leading to a deeper understanding of biological influences on human pro-sociality. To determine if an affective response motivates door-opening, rats receiving midazolam, a benzodiazepine anxiolytic, were tested in the helping behavior test. Midazolam treated rats showed less helping behavior than saline-treated rats or rats receiving no injection. Yet, midazolam-treated rats opened a restrainer containing chocolate, highlighting the socially specific effects of the anxiolytic. To determine if midazolam interferes with helping through a sympatholytic effect, the peripherally restricted beta-adrenergic receptor antagonist nadolol was administered; nadolol did not interfere with helping. The corticosterone response of rats exposed to a trapped cagemate was measured and compared to the rats' subsequent helping behavior. Rats with the greatest corticosterone responses showed the least helping behavior and those with the smallest responses showed the most consistent helping at the shortest latency. These results are discussed in terms of their implications for the interaction between stress and pro-social behavior. Finally, we observed that door-opening appeared to be reinforcing. A novel analytical tool was designed to interrogate the pattern of door-opening for signs that a rat's behavior on one session influenced his behavior on the next session. Results suggest that helping a trapped rat has a greater motivational value than does chocolate. In sum, this series of experiments clearly demonstrates the fundamental role of affect in motivating pro-social behavior in rodents and the need for a helper to resonate with the affect of a victim. PMID- 27375529 TI - Dissociating Perceptual Confidence from Discrimination Accuracy Reveals No Influence of Metacognitive Awareness on Working Memory. AB - Visual awareness is hypothesized to be intimately related to visual working memory (WM), such that information present in WM is thought to have necessarily been represented consciously. Recent work has challenged this longstanding view by demonstrating that visual stimuli rated by observers as unseen can nevertheless be maintained over a delay period. These experiments have been criticized, however, on the basis that subjective awareness ratings may contain response bias (e.g., an observer may report no awareness when in fact they had partial awareness). We mitigated this issue by investigating WM for visual stimuli that were matched for perceptual discrimination capacity (d'), yet which varied in subjective confidence ratings (so-called relative blindsight). If the degree of initial subjective awareness of a stimulus facilitates later maintenance of that information, WM performance should improve for stimuli encoded with higher confidence. In contrast, we found that WM performance did not benefit from higher visual discrimination confidence. This relationship was observed regardless of WM load (1 or 3). Insofar as metacognitive ratings (e.g., confidence, visibility) reflect visual awareness, these results challenge a strong relationship between conscious perception and WM using a paradigm that controls for discrimination accuracy and is less subject to response bias (since confidence is manipulated within subjects). Methodologically, we replicate prior efforts to induce relative blindsight using similar stimulus displays, providing a general framework for isolating metacognitive awareness in order to examine the function of consciousness. PMID- 27375530 TI - From Foreground to Background: How Task-Neutral Context Influences Contextual Cueing of Visual Search. AB - Selective attention determines the effectiveness of implicit contextual learning (e.g., Jiang and Leung, 2005). Visual foreground-background segmentation, on the other hand, is a key process in the guidance of attention (Wolfe, 2003). In the present study, we examined the impact of foreground-background segmentation on contextual cueing of visual search in three experiments. A visual search display, consisting of distractor 'L's and a target 'T', was overlaid on a task-neutral cuboid on the same depth plane (Experiment 1), on stereoscopically separated depth planes (Experiment 2), or spread over the entire display on the same depth plane (Experiment 3). Half of the search displays contained repeated target distractor arrangements, whereas the other half was always newly generated. The task-neutral cuboid was constant during an initial training session, but was either rotated by 90 degrees or entirely removed in the subsequent test sessions. We found that the gains resulting from repeated presentation of display arrangements during training (i.e., contextual-cueing effects) were diminished when the cuboid was changed or removed in Experiment 1, but remained intact in Experiments 2 and 3 when the cuboid was placed in a different depth plane, or when the items were randomly spread over the whole display but not on the edges of the cuboid. These findings suggest that foreground-background segmentation occurs prior to contextual learning, and only objects/arrangements that are grouped as foreground are learned over the course of repeated visual search. PMID- 27375531 TI - Chile: Acceptability of a Training Program for Depression Management in Primary Care. AB - BACKGROUND: In Chile, there are inconsistencies in the management of depression in primary care settings, and the National Depression Program, currently in effect, was implemented without a standardized training program. The objective of this study is to evaluate the acceptability of a training program on the management of depression for primary care health teams. METHODS: The study was a randomized controlled trial, and two primary centers from the Metropolitan Region of Santiago were randomly selected to carry out the intervention training program. Pre-post surveys were applied, to evaluate expectations and satisfaction with the intervention, respectively. Descriptive and content analysis was carried out. RESULT: The sample consisted of 41 health professionals, 56.1% of who reported that their expectations for the intervention were met. All of the training activities were evaluated with scores higher than 6.4 (on a 1-7 scale). The trainers, the methodology, and the learning environment were considered strengths and facilitators of the program, while the limited duration of the training, the logistical problems faced during part of the program, and the lack of educational material were viewed as weaknesses. CONCLUSION: The intervention was well accepted by primary health care teams. However, the clinical impact in patients still has to be evaluated. PMID- 27375532 TI - Theory of Mind and Reading Comprehension in Deaf and Hard-of-Hearing Signing Children. AB - Theory of Mind (ToM) is related to reading comprehension in hearing children. In the present study, we investigated progression in ToM in Swedish deaf and hard-of hearing (DHH) signing children who were learning to read, as well as the association of ToM with reading comprehension. Thirteen children at Swedish state primary schools for DHH children performed a Swedish Sign Language (SSL) version of the Wellman and Liu (2004) ToM scale, along with tests of reading comprehension, SSL comprehension, and working memory. Results indicated that ToM progression did not differ from that reported in previous studies, although ToM development was delayed despite age-appropriate sign language skills. Correlation analysis revealed that ToM was associated with reading comprehension and working memory, but not sign language comprehension. We propose that some factor not investigated in the present study, possibly represented by inference making constrained by working memory capacity, supports both ToM and reading comprehension and may thus explain the results observed in the present study. PMID- 27375533 TI - Manufacturing Magic and Computational Creativity. AB - This paper describes techniques in computational creativity, blending mathematical modeling and psychological insight, to generate new magic tricks. The details of an explicit computational framework capable of creating new magic tricks are summarized, and evaluated against a range of contemporary theories about what constitutes a creative system. To allow further development of the proposed system we situate this approach to the generation of magic in the wider context of other areas of application in computational creativity in performance arts. We show how approaches in these domains could be incorporated to enhance future magic generation systems, and critically review possible future applications of such magic generating computers. PMID- 27375534 TI - Bono Bo and Fla Mingo: Reflections of Speech Prosody in German Second Graders' Writing to Dictation. AB - Written German is characterized by an underrepresentation of prosody. During writing acquisition, children have to tackle the question which prosodic features are realized by what means - if any. We examined traces of speech prosody in German children's writing to dictation. A sample of 79 second graders were asked to write down eight sentences to dictation. We analyzed three potential reflections of speech prosody in children's dictations: (a) Merging of preposition and definite article, potentially preferred after monosyllabic prepositions as in this case preposition and article may melt to the canonical trochaic foot in German. (b) The introduction of orthographically inadequate graphemic border markings within trisyllabic animal names, respecting borders of prosodic units like foot or syllable. (c) Omissions of the definite article in non-optimal prosodic positions, deviating from the preferred strong-weak rhythm. The occurrence of border markings was evaluated via graded perceptual judgments. We found no evidence for inter-word border markings being influenced by prosodic context, probably due to a ceiling effect. However, word-internal markings within animal names, although rarely occurring in general, were clearly influenced by prosodic structure: Most of them were produced at borders of feet or syllables, while significantly fewer markings were perceived at borders of syllable constituents or within consonant clusters. Moreover, we observed significantly more omissions of the definite article in non-optimal prosodic positions compared to potentially optimal positions. Thus, our results provide first evidence from writing acquisition for prosodic influences on writing in a language with scarce graphemic marking of prosody. PMID- 27375535 TI - Molecular Signatures of Natural Selection for Polymorphic Genes of the Human Dopaminergic and Serotonergic Systems: A Review. AB - A large body of research has examined the behavioral and mental health consequences of polymorphisms in genes of the dopaminergic and serotonergic systems. Along with this, there has been considerable interest in the possibility that these polymorphisms have developed and/or been maintained due to the action of natural selection. Episodes of natural selection on a gene are expected to leave molecular "footprints" in the DNA sequences of the gene and adjacent genomic regions. Here we review the research literature investigating molecular signals of selection for genes of the dopaminergic and serotonergic systems. The gene SLC6A4, which codes for a serotonin transport protein, was the one gene for which there was consistent support from multiple studies for a selective episode. Positive selection on SLC6A4 appears to have been initiated ~ 20-25,000 years ago in east Asia and possibly in Europe. There are scattered reports of molecular signals of selection for other neurotransmitter genes, but these have generally failed at replication across studies. In spite of speculation in the literature about selection on these genes, current evidence from population genomic analyses supports selectively neutral processes, such as genetic drift and population dynamics, as the principal drivers of recent evolution in dopaminergic and serotonergic genes other than SLC6A4. PMID- 27375536 TI - Abnormal Default System Functioning in Depression: Implications for Emotion Regulation. AB - Depression is widely seen as the result of difficulties in regulating emotions. Based on neuroimaging studies on voluntary emotion regulation, neurobiological models have focused on the concept of cognitive control, considering emotion regulation as a shift toward involving controlled processes associated with activation of the prefrontal and parietal executive areas, instead of responding automatically to emotional stimuli. According to such models, the weaker executive area activation observed in depressed patients is attributable to a lack of cognitive control over negative emotions. Going beyond the concept of cognitive control, psychodynamic models describe the development of individuals' capacity to regulate their emotional states in mother-infant interactions during childhood, through the construction of the representation of the self, others, and relationships. In this mini-review, we link these psychodynamic models with recent findings regarding the abnormal functioning of the default system in depression. Consistently with psychodynamic models, psychological functions associated with the default system include self-related processing, semantic processes, and implicit forms of emotion regulation. The abnormal activation of the default system observed in depression may explain the dysfunctional aspects of emotion regulation typical of the condition, such as an exaggerated negative self-focus and rumination on self-esteem issues. We also discuss the clinical implications of these findings with reference to the therapeutic relationship as a key tool for revisiting impaired or distorted representations of the self and relational objects. PMID- 27375537 TI - Tuned In Emotion Regulation Program Using Music Listening: Effectiveness for Adolescents in Educational Settings. AB - This paper presents an effectiveness study of Tuned In, a novel emotion regulation intervention that uses participant selected music to evoke emotions in session and teaches participants emotional awareness and regulation skills. The group program content is informed by a two dimensional model of emotion (arousal, valence), along with music psychology theories about how music evokes emotional responses. The program has been evaluated in two samples of adolescents: 41 "at risk" adolescents (76% males; M age = 14.8 years) attending an educational re engagement program and 216 students (100% females; M age = 13.6 years) attending a mainstream secondary school. Results showed significant pre- to post-program improvements in measures of emotion awareness, identification, and regulation (p < 0.01 to p = 0.06 in the smaller "at risk" sample and all p < 0.001 in the mainstream school sample). Participant ratings of engagement and likelihood of using the strategies learned in the program were high. Tuned In shows promise as a brief emotion regulation intervention for adolescents, and these findings extend an earlier study with young adults. Tuned In is a-theoretical in regard to psychotherapeutic approach and could be integrated with other program components as required. PMID- 27375538 TI - Augmenting Instructional Animations with a Body Analogy to Help Children Learn about Physical Systems. AB - We investigated whether augmenting instructional animations with a body analogy (BA) would improve 10- to 13-year-old children's learning about class-1 levers. Children with a lower level of general math skill who learned with an instructional animation that provided a BA of the physical system, showed higher accuracy on a lever problem-solving reaction time task than children studying the instructional animation without this BA. Additionally, learning with a BA led to a higher speed-accuracy trade-off during the transfer task for children with a lower math skill, which provided additional evidence that especially this group is likely to be affected by learning with a BA. However, overall accuracy and solving speed on the transfer task was not affected by learning with or without this BA. These results suggest that providing children with a BA during animation study provides a stepping-stone for understanding mechanical principles of a physical system, which may prove useful for instructional designers. Yet, because the BA does not seem effective for all children, nor for all tasks, the degree of effectiveness of body analogies should be studied further. Future research, we conclude, should be more sensitive to the necessary degree of analogous mapping between the body and physical systems, and whether this mapping is effective for reasoning about more complex instantiations of such physical systems. PMID- 27375539 TI - Editorial: Is the Language Faculty Nonlinguistic? PMID- 27375540 TI - The Penefit of Salience: Salient Accented, but Not Unaccented Words Reveal Accent Adaptation Effects. AB - In two eye-tracking experiments, the effects of salience in accent training and speech accentedness on spoken-word recognition were investigated. Salience was expected to increase a stimulus' prominence and therefore promote learning. A training-test paradigm was used on native German participants utilizing an artificial German accent. Salience was elicited by two different criteria: production and listening training as a subjective criterion and accented (Experiment 1) and canonical test words (Experiment 2) as an objective criterion. During training in Experiment 1, participants either read single German words out loud and deliberately devoiced initial voiced stop consonants (e.g., Balken "beam" pronounced as (*) Palken), or they listened to pre-recorded words with the same accent. In a subsequent eye-tracking experiment, looks to auditorily presented target words with the accent were analyzed. Participants from both training conditions fixated accented target words more often than a control group without training. Training was identical in Experiment 2, but during test, canonical German words that overlapped in onset with the accented words from training were presented as target words (e.g., Palme-"palm tree" overlapped in onset with the training word (*) Palken) rather than accented words. This time, no training effect was observed; recognition of canonical word forms was not affected by having learned the accent. Therefore, accent learning was only visible when the accented test tokens in Experiment 1, which were not included in the test of Experiment 2, possessed sufficient salience based on the objective criterion "accent." These effects were not modified by the subjective criterion of salience from the training modality. PMID- 27375541 TI - Differences in Intrusive Memory Experiences in Post-traumatic Stress Disorder after Single, Re- and Prolonged Traumatization. AB - Intrusive memory experiences (IMEs) are a common symptom of post-traumatic stress disorder (PTSD). Sensory perceptions of IMEs in the PTSD context vary substantially. The present research examined 20 patients with a single trauma, 20 re-traumatized patients and 80 Holocaust-traumatized patients who suffered from PTSD. Our results revealed significant differences in IME frequency based on the types of trauma experience. The findings suggest that patients with prolonged (Holocaust) traumata suffered from visual (65%) and combined visual/acoustic intrusive memories (29%), whereas visual memory experiences were most frequent (90%) among single-trauma patients. The trauma experience and the intrusive memory trigger stimulus were interdependent. The type of trauma critically affects the traumatic experience. Future studies should focus on these findings to improve PTSD therapeutic options. PMID- 27375542 TI - When Neuroscience 'Touches' Architecture: From Hapticity to a Supramodal Functioning of the Human Brain. AB - In the last decades, the rapid growth of functional brain imaging methodologies allowed cognitive neuroscience to address open questions in philosophy and social sciences. At the same time, novel insights from cognitive neuroscience research have begun to influence various disciplines, leading to a turn to cognition and emotion in the fields of planning and architectural design. Since 2003, the Academy of Neuroscience for Architecture has been supporting 'neuro-architecture' as a way to connect neuroscience and the study of behavioral responses to the built environment. Among the many topics related to multisensory perceptual integration and embodiment, the concept of hapticity was recently introduced, suggesting a pivotal role of tactile perception and haptic imagery in architectural appraisal. Arguments have thus risen in favor of the existence of shared cognitive foundations between hapticity and the supramodal functional architecture of the human brain. Precisely, supramodality refers to the functional feature of defined brain regions to process and represent specific information content in a more abstract way, independently of the sensory modality conveying such information to the brain. Here, we highlight some commonalities and differences between the concepts of hapticity and supramodality according to the distinctive perspectives of architecture and cognitive neuroscience. This comparison and connection between these two different approaches may lead to novel observations in regard to people-environment relationships, and even provide empirical foundations for a renewed evidence-based design theory. PMID- 27375543 TI - Discovery of a Recursive Principle: An Artificial Grammar Investigation of Human Learning of a Counting Recursion Language. AB - Learning is typically understood as a process in which the behavior of an organism is progressively shaped until it closely approximates a target form. It is easy to comprehend how a motor skill or a vocabulary can be progressively learned-in each case, one can conceptualize a series of intermediate steps which lead to the formation of a proficient behavior. With grammar, it is more difficult to think in these terms. For example, center embedding recursive structures seem to involve a complex interplay between multiple symbolic rules which have to be in place simultaneously for the system to work at all, so it is not obvious how the mechanism could gradually come into being. Here, we offer empirical evidence from a new artificial language (or "artificial grammar") learning paradigm, Locus Prediction, that, despite the conceptual conundrum, recursion acquisition occurs gradually, at least for a simple formal language. In particular, we focus on a variant of the simplest recursive language, a (n) b (n) , and find evidence that (i) participants trained on two levels of structure (essentially ab and aabb) generalize to the next higher level (aaabbb) more readily than participants trained on one level of structure (ab) combined with a filler sentence; nevertheless, they do not generalize immediately; (ii) participants trained up to three levels (ab, aabb, aaabbb) generalize more readily to four levels than participants trained on two levels generalize to three; (iii) when we present the levels in succession, starting with the lower levels and including more and more of the higher levels, participants show evidence of transitioning between the levels gradually, exhibiting intermediate patterns of behavior on which they were not trained; (iv) the intermediate patterns of behavior are associated with perturbations of an attractor in the sense of dynamical systems theory. We argue that all of these behaviors indicate a theory of mental representation in which recursive systems lie on a continuum of grammar systems which are organized so that grammars that produce similar behaviors are near one another, and that people learning a recursive system are navigating progressively through the space of these grammars. PMID- 27375544 TI - The Dark Side of Top Level Sport: An Autobiographic Study of Depressive Experiences in Elite Sport Performers. AB - The general and sport psychology research converge to point to a complex relationship between depressive experiences and human performance. The purpose of this study was to explore the depressive experiences of top level athletes and the relationship of such experiences with sport performance. Twelve autobiographies of elite athletes representing eight sports were analyzed. The autobiographical analysis was informed by narrative tradition, using three types of narrative analysis: categorical content, categorical form, and holistic content. The analysis revealed a temporal aspect to the depressive experiences that the athletes reported. Initially, sport represented a form of escape from the depressive symptoms which had been exacerbated by both external stressors (e.g., experiencing bereavement) and internal stressors (e.g., low self-esteem). However, in time, the athletes typically reached a stage when the demands of their sport shifted from being facilitative to being debilitative in nature with an intensification of their depressive symptoms. This was accompanied by deliberations about continuing their engagement in sport and an acceptance that they could no longer escape from their symptoms, with or without sport. The findings extend the extant literature by suggesting a reciprocal relationship between depressive experiences and sport performance, and they support the general psychology literature relating to the negative impact of depression on performance. The applied implications of these findings are discussed emphasizing the importance of early identification of depressive symptoms and the adoption of a proactive approach in the prevention and management of symptoms. PMID- 27375545 TI - A Comparison of Estimation Methods for a Multi-unidimensional Graded Response IRT Model. AB - This study compared several parameter estimation methods for multi-unidimensional graded response models using their corresponding statistical software programs and packages. Specifically, we compared two marginal maximum likelihood (MML) approaches (Bock-Aitkin expectation-maximum algorithm, adaptive quadrature approach), four fully Bayesian algorithms (Gibbs sampling, Metropolis-Hastings, Hastings-within-Gibbs, blocked Metropolis), and the Metropolis-Hastings Robbins Monro (MHRM) algorithm via the use of IRTPRO, BMIRT, and MATLAB. Simulation results suggested that, when the intertrait correlation was low, these estimation methods provided similar results. However, if the dimensions were moderately or highly correlated, Hastings-within-Gibbs had an overall better parameter recovery of item discrimination and intertrait correlation parameters. The performances of these estimation methods with different sample sizes and test lengths are also discussed. PMID- 27375546 TI - The Effects of External Jugular Compression Applied during Head Impact Exposure on Longitudinal Changes in Brain Neuroanatomical and Neurophysiological Biomarkers: A Preliminary Investigation. AB - OBJECTIVES: Utilize a prospective in vivo clinical trial to evaluate the potential for mild neck compression applied during head impact exposure to reduce anatomical and physiological biomarkers of brain injury. METHODS: This project utilized a prospective randomized controlled trial to evaluate effects of mild jugular vein (neck) compression (collar) relative to controls (no collar) during a competitive hockey season (males; 16.3 +/- 1.2 years). The collar was designed to mildly compress the jugular vein bilaterally with the goal to increase intracranial blood volume to reduce risk of brain slosh injury during head impact exposure. Helmet sensors were used to collect daily impact data in excess of 20 g (games and practices) and the primary outcome measures, which included changes in white matter (WM) microstructure, were assessed by diffusion tensor imaging (DTI). Specifically, four DTI measures: fractional anisotropy, mean diffusivity (MD), axial diffusivity, and radial diffusivity (RD) were used in the study. These metrics were analyzed using the tract-based Spatial Statistics (TBSS) approach - a voxel-based analysis. In addition, electroencephalography-derived event-related potentials were used to assess changes in brain network activation (BNA) between study groups. RESULTS: For athletes not wearing the collar, DTI measures corresponding to a disruption of WM microstructure, including MD and RD, increased significantly from pre-season to mid-season (p < 0.05). Athletes wearing the collar did not show a significant change in either MD or RD despite similar accumulated linear accelerations from head impacts (p > 0.05). In addition to these anatomical findings, electrophysiological network analysis of the degree of congruence in the network electrophysiological activation pattern demonstrated concomitant changes in brain network dynamics in the non-collar group only (p < 0.05). Similar to the DTI findings, the increased change in BNA score in the non-collar relative to the collar group was statistically significant (p < 0.01). Changes in DTI outcomes were also directly correlated with altered brain network dynamics (r = 0.76; p < 0.05) as measured by BNA. CONCLUSION: Group differences in the longitudinal changes in both neuroanatomical and electrophysiological measures, as well as the correlation between the measures, provide initial evidence indicating that mild jugular vein compression may have reduced alterations in the WM response to head impacts during a competitive hockey season. The data indicate sport-related alterations in WM microstructure were ameliorated by application of jugular compression during head impact exposure. These results may lead to a novel line of research inquiry to evaluate the effects of protecting the brain from sports-related head impacts via optimized intracranial fluid dynamics. PMID- 27375547 TI - Restoration of Upper Limb Function in an Individual with Cervical Spondylotic Myelopathy using Functional Electrical Stimulation Therapy: A Case Study. AB - Non-traumatic spinal cord pathology is responsible for 25-52% of all spinal cord lesions. Studies have revealed that spinal stenosis accounts for 16-21% of spinal cord injury (SCI) admissions. Impaired grips as well as slow unskilled hand and finger movements are the most common complaints in patients with spinal cord disorders, such as myelopathy secondary to cervical spondylosis. In the past, our team carried out couple of successful clinical trials, including two randomized control trials, showing that functional electrical stimulation therapy (FEST) can restore voluntary reaching and/or grasping function, in people with stroke and traumatic SCI. Motivated by this success, we decided to examine changes in the upper limb function following FEST in a patient who suffered loss of hand function due to myelopathy secondary to cervical spondylosis. The participant was a 61-year-old male who had C3-C7 posterior laminectomy and instrumented fusion for cervical myelopathy. The participant presented with progressive right hand weakness that resulted in his inability to voluntarily open and close the hand and to manipulate objects unilaterally with his right hand. The participant was enrolled in the study ~22 months following initial surgical intervention. Participant was assessed using Toronto Rehabilitation Institute's Hand Function Test (TRI-HFT), Action Research Arm Test (ARAT), Functional Independence Measure (FIM), and Spinal Cord Independence Measure (SCIM). The pre-post differences in scores on all measures clearly demonstrated improvement in voluntary hand function following 15 1-h FEST sessions. The changes observed were meaningful and have resulted in substantial improvement in performance of activities of daily living. These results provide preliminary evidence that FEST has a potential to improve upper limb function in patients with non-traumatic SCI, such as myelopathy secondary to cervical spondylosis. PMID- 27375548 TI - Minor Stroke and Transient Ischemic Attack: Research and Practice. AB - A majority of patients with ischemic stroke present with mild deficits for which aggressive management is not often pursued. Comprehensive work-up and appropriate intervention for minor strokes and transient ischemic attacks (TIAs) point toward better patient outcomes, lower costs, and fewer cases of disability. Imaging is a key modality to guide treatment and predict stroke recurrence. Patients with large vessel occlusions have been found to suffer worse outcomes and could benefit from intervention. Whether intravenous thrombolytic therapy decreases disability in minor stroke patients and whether acute endovascular intervention improves functional outcomes in patients with minor stroke and known large vessel occlusion remain controversial. Studies are ongoing to determine ideal antiplatelet therapy for stroke and TIA, while ongoing statin therapy, surgical management for patients with carotid stenosis, and anticoagulation for patients with atrial fibrillation have all been proven to decrease the rate of stroke recurrence and improve outcomes. This review summarizes the current evidence and discusses the standard of care for patients with minor stroke and TIA. PMID- 27375550 TI - Effects of Neuroendocrine CB1 Activity on Adult Leydig Cells. AB - Endocannabinoids control male reproduction acting at central and local level via cannabinoid receptors. The cannabinoid receptor CB1 has been characterized in the testis, in somatic and germ cells of mammalian and non-mammalian animal models, and its activity related to Leydig cell differentiation, steroidogenesis, spermiogenesis, sperm quality, and maturation. In this short review, we provide a summary of the insights concerning neuroendocrine CB1 activity in male reproduction focusing on adult Leydig cell ontogenesis and steroid biosynthesis. PMID- 27375549 TI - Sex Differences in Insular Cortex Gyri Responses to the Valsalva Maneuver. AB - Sex differences in autonomic regulation may underlie cardiovascular disease variations between females and males. One key autonomic brain region is the insular cortex, which typically consists of five main gyri in each hemisphere, and shows a topographical organization of autonomic function across those gyri. The present study aims to identify possible sex differences in organization of autonomic function in the insula. We studied brain functional magnetic resonance imaging (fMRI) responses to a series of four 18-s Valsalva maneuvers in 22 healthy females (age +/- SD: 50.0 +/- 7.9 years) and 36 healthy males (45.3 +/- 9.2 years). Comparisons of heart rate (HR) and fMRI signals were performed with repeated measures ANOVA (threshold P < 0.05 for all findings). All subjects achieved the target 30 mmHg expiratory pressure for all challenges. Typical HR responses were elicited by the maneuver, including HR increases from ~4 s into the strain period (Phase II) and rapid declines to below baseline 5-10 s, following strain release (Phase IV). Small, but significant, sex differences in HR percent change occurred during the sympathetic-dominant Phase II (female < male) and parasympathetic-dominant Phase IV (female > male, i.e., greater undershoot in males). The insular cortices showed similar patterns in all gyri, with greater signal decreases in males than females. Both sexes exhibited an anterior-posterior topographical organization of insular responses during Phase II, with anterior gyri showing higher responses than more posterior gyri. The exception was the right anterior-most gyrus in females, which had lower responses than the four other right gyri. Responses were lateralized, with right-sided dominance during Phase II in both sexes, except the right anterior-most gyrus in females, which showed lower responses than the left. The findings confirm the anterior and right-sided sympathetic dominance of the insula. Although sex differences were prominent in response magnitude, organization differences between males and females were limited to the right anterior-most gyrus, which showed a lower fMRI response in females vs. males (and vs. other gyri in females). The sex differences suggest a possible differing baseline state of brain physiology or tonic functional activity between females and males, especially in the right anterior-most gyrus. PMID- 27375551 TI - Ultrasound-Guided Percutaneous Ethanol Injection Protocol to Treat Solid and Mixed Thyroid Nodules. AB - CONTEXT: Ultrasound (US)-guided percutaneous ethanol injection (PEI) has been proposed for treatment of benign thyroid nodules (TNs). However, there is no consensus for the optimal amount of ethanol injection, number of applications, and time to re-evaluation in order to achieve maximum volume reduction with minimum adverse effects. OBJECTIVE: The purpose of the present study was to analyze the effectiveness of an US-guided PEI protocol to treat solid and mixed TNs based on a new target outcome. PATIENTS AND METHODS: We performed a prospective study evaluating the results of PEI in 52 patients with benign solid and mixed TNs. The ethanol dose was fixed in 30% of the nodular volume per session. Patients returned 1 month after each session for US re-evaluation. Therapeutic success was defined as volume reduction of at least 30% associated with disappearance of clinical symptoms and a complete esthetic satisfaction reported by the patient. RESULTS: We performed a mean of 2.8 +/- 1.9 PEI sessions, with an average total volume of ethanol injected of 9.1 +/- 10.3 ml, and a follow-up time of 10.0 +/- 8.7 months. There was a reduction of at least 50% of the initial nodular volume in 33 patients (63.5%). In 11 patients (21.2%), the reduction did not reach 50% (mean reduction of 31 +/- 11%), but 6 of them reported esthetically satisfactory results and treatment was stopped. Our therapeutic success rate considering the patients with esthetic improvement was 75%. There were no severe complications. CONCLUSION: Our protocol is effective and safe to treat solid and mixed benign TNs based on our established outcome. PMID- 27375552 TI - Genetic Rodent Models of Obesity-Associated Ovarian Dysfunction and Subfertility: Insights into Polycystic Ovary Syndrome. AB - Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women and a leading cause of female infertility worldwide. Defined clinically by the presence of hyperandrogenemia and oligomenorrhoea, PCOS represents a state of hormonal dysregulation, disrupted ovarian follicle dynamics, and subsequent oligo or anovulation. The syndrome's prevalence is attributed, at least partly, to a well-established association with obesity and insulin resistance (IR). Indeed, the presence of severe PCOS in human genetic obesity and IR syndromes supports a causal role for IR in the pathogenesis of PCOS. However, the molecular mechanisms underlying this causality, as well as the important role of hyperandrogenemia, remain poorly elucidated. As such, treatment of PCOS is necessarily empirical, focusing on symptom alleviation. The generation of knockout and transgenic rodent models of obesity and IR offers a promising platform in which to address mechanistic questions about reproductive dysfunction in the context of metabolic disease. Similarly, the impact of primary perturbations in rodent gonadotrophin or androgen signaling has been interrogated. However, the insights gained from such models have been limited by the relatively poor fidelity of rodent models to human PCOS. In this mini review, we evaluate the ovarian phenotypes associated with rodent models of obesity and IR, including the extent of endocrine disturbance, ovarian dysmorphology, and subfertility. We compare them to both human PCOS and other animal models of the syndrome (genetic and hormonal), explore reasons for their discordance, and consider the new opportunities that are emerging to better understand and treat this important condition. PMID- 27375553 TI - The Role of Gut Microflora and the Cholinergic Anti-inflammatory Neuroendocrine System in Diabetes Mellitus. AB - The obesity epidemic has drastically impacted the state of health care in the United States. Paralleling this epidemic is the incidence of diabetes mellitus, with a notable shift toward a much younger age of onset. While central to the pathogenesis of diabetes associated with obesity is the role of inflammation attributed to "adiposopathy." Emerging data suggest that changes in sympathetic/parasympathetic balance regulated by the brain precede changes in the inflammatory cascade. It has now been established that the gut microflora contributes significantly to the activation and inhibition of autonomic control and impact the set of the neuroinflammatory inhibitory reflex mediated by the cholinergic nervous system. There has been a paradigm shift toward further investigating commensal bacteria in the pathogenesis of obesity and diabetes mellitus and its complications, as dysbiosis is thought to play a pivotal role in diabetic-associated disorders. This paper is intended to evaluate the role of intestinal dysbiosis in the pathogenesis of diabetes mellitus and examine the potential for restoration of balance via use of probiotics. PMID- 27375554 TI - Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research. AB - Although technical problems of thyroid testing have largely been resolved by modern assay technology, biological variation remains a challenge. This applies to subclinical thyroid disease, non-thyroidal illness syndrome, and those 10% of hypothyroid patients, who report impaired quality of life, despite normal thyrotropin (TSH) concentrations under levothyroxine (L-T4) replacement. Among multiple explanations for this condition, inadequate treatment dosage and monotherapy with L-T4 in subjects with impaired deiodination have received major attention. Translation to clinical practice is difficult, however, since univariate reference ranges for TSH and thyroid hormones fail to deliver robust decision algorithms for therapeutic interventions in patients with more subtle thyroid dysfunctions. Advances in mathematical and simulative modeling of pituitary-thyroid feedback control have improved our understanding of physiological mechanisms governing the homeostatic behavior. From multiple cybernetic models developed since 1956, four examples have also been translated to applications in medical decision-making and clinical trials. Structure parameters representing fundamental properties of the processing structure include the calculated secretory capacity of the thyroid gland (SPINA-GT), sum activity of peripheral deiodinases (SPINA-GD) and Jostel's TSH index for assessment of thyrotropic pituitary function, supplemented by a recently published algorithm for reconstructing the personal set point of thyroid homeostasis. In addition, a family of integrated models (University of California Los Angeles platform) provides advanced methods for bioequivalence studies. This perspective article delivers an overview of current clinical research on the basis of mathematical thyroid models. In addition to a summary of large clinical trials, it provides previously unpublished results of validation studies based on simulation and clinical samples. PMID- 27375555 TI - Possible Pharmacological Approach Targeting Endoplasmic Reticulum Stress to Ameliorate Leptin Resistance in Obesity. AB - Obesity is associated with metabolic syndrome, such as diabetes, hypertension, and hyperlipidemia. Therefore, drug development for the treatment of obesity is needed. Leptin is an anti-obesity hormone that inhibits food intake and increases energy metabolism, and, as such, treatments involving leptin were expected to be beneficial for obesity; however, since most obese patients are in a state of leptin resistance, these treatments may not be useful. Therefore, the amelioration of leptin resistance has recently been attracting interest as a treatment for obesity. The mechanisms underlying the development of leptin resistance need to be elucidated in more detail. Endoplasmic reticulum (ER) stress was recently suggested to be involved in the pathogenesis of leptin resistance. The molecular mechanisms responsible for leptin resistance and possible pharmacological treatments for obesity have been discussed herein, with a focus on ER stress. PMID- 27375557 TI - Genome-Centric Analysis of Microbial Populations Enriched by Hydraulic Fracture Fluid Additives in a Coal Bed Methane Production Well. AB - Coal bed methane (CBM) is generated primarily through the microbial degradation of coal. Despite a limited understanding of the microorganisms responsible for this process, there is significant interest in developing methods to stimulate additional methane production from CBM wells. Physical techniques including hydraulic fracture stimulation are commonly applied to CBM wells, however the effects of specific additives contained in hydraulic fracture fluids on native CBM microbial communities are poorly understood. Here, metagenomic sequencing was applied to the formation waters of a hydraulically fractured and several non fractured CBM production wells to determine the effect of this stimulation technique on the in-situ microbial community. The hydraulically fractured well was dominated by two microbial populations belonging to the class Phycisphaerae (within phylum Planctomycetes) and candidate phylum Aminicenantes. Populations from these phyla were absent or present at extremely low abundance in non fractured CBM wells. Detailed metabolic reconstruction of near-complete genomes from these populations showed that their high relative abundance in the hydraulically fractured CBM well could be explained by the introduction of additional carbon sources, electron acceptors, and biocides contained in the hydraulic fracture fluid. PMID- 27375556 TI - Role of Protein Phosphorylation and Tyrosine Phosphatases in the Adrenal Regulation of Steroid Synthesis and Mitochondrial Function. AB - In adrenocortical cells, adrenocorticotropin (ACTH) promotes the activation of several protein kinases. The action of these kinases is linked to steroid production, mainly through steroidogenic acute regulatory protein (StAR), whose expression and activity are dependent on protein phosphorylation events at genomic and non-genomic levels. Hormone-dependent mitochondrial dynamics and cell proliferation are functions also associated with protein kinases. On the other hand, protein tyrosine dephosphorylation is an additional component of the ACTH signaling pathway, which involves the "classical" protein tyrosine phosphatases (PTPs), such as Src homology domain (SH) 2-containing PTP (SHP2c), and members of the MAP kinase phosphatase (MKP) family, such as MKP-1. PTPs are rapidly activated by posttranslational mechanisms and participate in hormone-stimulated steroid production. In this process, the SHP2 tyrosine phosphatase plays a crucial role in a mechanism that includes an acyl-CoA synthetase-4 (Acsl4), arachidonic acid (AA) release and StAR induction. In contrast, MKPs in steroidogenic cells have a role in the turn-off of the hormonal signal in ERK dependent processes such as steroid synthesis and, perhaps, cell proliferation. This review analyzes the participation of these tyrosine phosphates in the ACTH signaling pathway and the action of kinases and phosphatases in the regulation of mitochondrial dynamics and steroid production. In addition, the participation of kinases and phosphatases in the signal cascade triggered by different stimuli in other steroidogenic tissues is also compared to adrenocortical cell/ACTH and discussed. PMID- 27375558 TI - Listeria ivanovii Infection in Mice: Restricted to the Liver and Lung with Limited Replication in the Spleen. AB - Listeria monocytogenes (LM) vectors have shown much promise in delivery of viral and tumor antigens for the development of vaccines. L. ivanovii (LI) is a closely related bacterium with a similar intracellular life cycle that may offer advantages over LM because it is not a human pathogen, but can infect other animal species. Recent studies show that recombinant LI expressing Mycobacterium tuberculosis antigens is effective in inducing protective immunity in mouse models, demonstrating the potential of LI as a live vaccine vector. However, a key barrier in the development of LI into a live vaccine vector is that its pathogenic and immunogenic characteristics have yet to be fully understood. Therefore, in this research, C57BL/6J mice were inoculated with LM or LI intravenously or intranasally, and bacterial loads, histopathologic changes, and cytokine production were determined at indicated days post inoculation. Results showed that after intravenous infection with LM or LI, bacteria were found proliferating in the liver, spleen, and lung. However, LI could only reach a heavy burden in the liver and its ability to multiply and to resist host immunity seemed limited in the spleen and lung. After intranasal inoculation with LI, bacteria were mainly localized in the lung and failed to infect liver or spleen, while LM could. In organs with heavy LI burden, lesions were isolated, localized and densely packed, compared to lesions caused by LM, which were invasive. In the liver of intravenously inoculated mice and lung of intranasally inoculate mice, LI was able to elicit comparable cytokine production with LM and cause less severe histopathologic damages, and thus could be considered as a vector for treating or preventing hepatic or pulmonary diseases. PMID- 27375559 TI - Comparative Genomics and Proteomic Analysis of Four Non-tuberculous Mycobacterium Species and Mycobacterium tuberculosis Complex: Occurrence of Shared Immunogenic Proteins. AB - The Esx and PE/PPE families of proteins are among the most immunodominant mycobacterial antigens and have thus been the focus of research to develop vaccines and immunological tests for diagnosis of bovine and human tuberculosis, mainly caused by Mycobacterium bovis and Mycobacterium tuberculosis, respectively. In non-tuberculous mycobacteria (NTM), multiple copies of genes encoding homologous proteins have mainly been identified in pathogenic Mycobacterium species phylogenically related to Mycobacterium tuberculosis and Mycobacterium bovis. Only ancestral copies of these genes have been identified in nonpathogenic NTM species like Mycobacterium smegmatis, Mycobacterium sp. KMS, Mycobacterium sp. MCS, and Mycobacterium sp. JLS. In this study we elucidated the genomes of four nonpathogenic NTM species, viz Mycobacterium komanii sp. nov., Mycobacterium malmesburii sp. nov., Mycobacterium nonchromogenicum, and Mycobacterium fortuitum ATCC 6841. These genomes were investigated for genes encoding for the Esx and PE/PPE (situated in the esx cluster) family of proteins as well as adjacent genes situated in the ESX-1 to ESX-5 regions. To identify proteins actually expressed, comparative proteomic analyses of purified protein derivatives from three of the NTM as well as Mycobacterium kansasii ATCC 12478 and the commercially available purified protein derivatives from Mycobacterium bovis and Mycobacterium avium was performed. The genomic analysis revealed the occurrence in each of the four NTM, orthologs of the genes encoding for the Esx family, the PE and PPE family proteins in M. bovis and M. tuberculosis. The identification of genes of the ESX-1, ESX-3, and ESX-4 region including esxA, esxB, ppe68, pe5, and pe35 adds to earlier reports of these genes in nonpathogenic NTM like M. smegmatis, Mycobacterium sp. JLS and Mycobacterium KMS. This report is also the first to identify esxN gene situated within the ESX-5 locus in M. nonchromogenicum. Our proteomics analysis identified a total of 609 proteins in the six PPDs and 22 of these were identified as shared between PPD of M.bovis and one or more of the NTM PPDs. Previously characterized M tuberculosis/M. bovis homologous immunogenic proteins detected in one or more of the nonpathogenic NTM in this study included CFP-10 (detected in M. malmesburii sp. nov. PPD), GroES (detected in all NTM PPDs but M. malmesburii sp. nov.), DnaK (detected in all NTM PPDs), and GroEL (detected in all NTM PPDs). This study confirms reports that the ESX-1, ESX-3, and ESX-4 regions are ancestral regions and thus found in the genomes of most mycobacteria. Identification of NTM homologs of immunogenic proteins warrants further investigation of their ability to cause cross-reactive immune responses with MTBC antigens. PMID- 27375560 TI - A Prescription for Resistance: Management of Staphylococcal Skin Abscesses by General Practitioners in Australia. AB - OBJECTIVES: We investigated the management of staphylococcal abscesses (boils) by general practitioners (GPs) in the context of rising antibiotic resistance in community strains of Staphylococcus aureus. DESIGN, SETTING, PARTICIPANTS: We analyzed patient-reported management of 66 cases of uncomplicated skin abscesses from the frequency matched methicillin-resistant S. aureus (MRSA) and methicillin sensitive S. aureus (MSSA) Community-Onset Staphylococcus aureus Household Cohort (COSAHC) study (Melbourne, Australia, 2008-2012). Susceptibilities in all cases were known: 50/66 abscesses were caused by MRSA. In order to investigate GP reported management of staphylococcal abscesses, we surveyed a random subset of GPs, from the COSAHC study (41), and of GPs (39) who used the same community based pathology service (December 2011-May 2012). MAIN OUTCOME MEASURES: Patient outcomes, antibiotics prescribed, antibiotic resistance profiles of infecting strains, rates of incision and drainage (I&D), and attitudes to ordering microbiological cultures. RESULTS: MRSA was three times more likely to be cultured from an abscess than MSSA. Patient-reported management revealed 100% were prescribed antibiotics and only 60.6% had I&D. Of those 85% who remembered their prescription(s), 81% of MRSA cases and 23% of MSSA cases initially received inactive antibiotics. Repeat GP visits where antibiotics were changed occurred in 45 MRSA and 7 MSSA cases, although at least 33% of subsequent prescriptions were inactive for the MRSA infections. Patients treated with I&D and antibiotics did no better than those treated with only I&D, regardless of the antibiotic activity. In the GP surveys, 89% reported I&D, with or without antibiotics, to be their preferred management. Only 29.9% of GPs would routinely swab abscesses. CONCLUSION: The recommended management of uncomplicated Staphylococcus abscesses is I&D without antibiotics to reduce exposure to unnecessary antibiotics. In our study, I&D was performed in only 60.6% of 66 patients, and antibiotics were always prescribed. The prescribed antibiotics were frequently inactive and often changed, and did not appear to affect patient recovery. Our results show that community GPs can confidently reduce their use of antibiotics for patients with skin abscesses and should be aware that MRSA is a much more common in this type of infection. PMID- 27375561 TI - Aflatoxin-Exposure of Vibrio gazogenes as a Novel System for the Generation of Aflatoxin Synthesis Inhibitors. AB - Aflatoxin is a mycotoxin and a secondary metabolite, and the most potent known liver carcinogen that contaminates several important crops, and represents a significant threat to public health and the economy. Available approaches reported thus far have been insufficient to eliminate this threat, and therefore provide the rational to explore novel methods for preventing aflatoxin accumulation in the environment. Many terrestrial plants and microbes that share ecological niches and encounter the aflatoxin producers have the ability to synthesize compounds that inhibit aflatoxin synthesis. However, reports of natural aflatoxin inhibitors from marine ecosystem components that do not share ecological niches with the aflatoxin producers are rare. Here, we show that a non pathogenic marine bacterium, Vibrio gazogenes, when exposed to low non-toxic doses of aflatoxin B1, demonstrates a shift in its metabolic output and synthesizes a metabolite fraction that inhibits aflatoxin synthesis without affecting hyphal growth in the model aflatoxin producer, Aspergillus parasiticus. The molecular mass of the predominant metabolite in this fraction was also different from the known prodigiosins, which are the known antifungal secondary metabolites synthesized by this Vibrio. Gene expression analyses using RT-PCR demonstrate that this metabolite fraction inhibits aflatoxin synthesis by down regulating the expression of early-, middle-, and late- growth stage aflatoxin genes, the aflatoxin pathway regulator, aflR and one global regulator of secondary metabolism, laeA. Our study establishes a novel system for generation of aflatoxin synthesis inhibitors, and emphasizes the potential of the under explored Vibrio's silent genome for generating new modulators of fungal secondary metabolism. PMID- 27375562 TI - Prevalence of Staphylococcus aureus and Methicillin-Resistant Staphylococcus aureus in Retail Ready-to-Eat Foods in China. AB - Staphylococcus aureus, particularly methicillin-resistant S.aureus (MRSA), is a life-threatening pathogen in humans, and its presence in food is a public health concern. MRSA has been identified in foods in China, but little information is available regarding MRSA in ready-to-eat (RTE) foods. We aimed to investigate the prevalence of S. aureus and MRSA in Chinese retail RTE foods. All isolated S. aureus were tested for antimicrobial susceptibility, and MRSA isolates were further characterized by multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing. Of the 550 RTE foods collected from 2011 to 2014, 69 (12.5%) were positive for S. aureus. Contamination levels were mostly in the range of 0.3-10 most probable number (MPN)/g, with five samples exceeding 10 MPN/g. Of the 69 S. aureus isolates, seven were identified as MRSA by cefoxitin disc diffusion test. Six isolates were mecA-positive, while no mecC positive isolates were identified. In total, 75.8% (47/62) of the methicillin susceptible S. aureus isolates and all of the MRSA isolates were resistant to three or more antibiotics. Amongst the MRSA isolates, four were identified as community-acquired strains (ST59-MRSA-IVa (n = 2), ST338-MRSA-V, ST1-MRSA-V), while one was a livestock-associated strain (ST9, harboring an unreported SCCmec type 2C2). One novel sequence type was identified (ST3239), the SCCmec gene of which could not be typed. Overall, our findings showed that Chinese retail RTE foods are likely vehicles for transmission of multidrug-resistant S. aureus and MRSA lineages. This is a serious public health risk and highlights the need to implement good hygiene practices. PMID- 27375563 TI - Differential Regulation of c-di-GMP Metabolic Enzymes by Environmental Signals Modulates Biofilm Formation in Yersinia pestis. AB - Cyclic diguanylate (c-di-GMP) is essential for Yersinia pestis biofilm formation, which is important for flea-borne blockage-dependent plague transmission. Two diguanylate cyclases (DGCs), HmsT and HmsD and one phosphodiesterase (PDE), HmsP are responsible for the synthesis and degradation of c-di-GMP in Y. pestis. Here, we systematically analyzed the effect of various environmental signals on regulation of the biofilm phenotype, the c-di-GMP levels, and expression of HmsT, HmsD, and HmsP in Y. pestis. Biofilm formation was higher in the presence of non lethal high concentration of CaCl2, MgCl2, CuSO4, sucrose, sodium dodecyl sulfate, or dithiothreitol, and was lower in the presence of FeCl2 or NaCl. In addition, we found that HmsD plays a major role in biofilm formation in acidic or redox environments. These environmental signals differentially regulated expression of HmsT, HmsP and HmsD, resulting in changes in the intracellular levels of c-di-GMP in Y. pestis. Our results suggest that bacteria can sense various environmental signals, and differentially regulate activity of DGCs and PDEs to coordinately regulate and adapt metabolism of c-di-GMP and biofilm formation to changing environments. PMID- 27375564 TI - HoloVir: A Workflow for Investigating the Diversity and Function of Viruses in Invertebrate Holobionts. AB - Abundant bioinformatics resources are available for the study of complex microbial metagenomes, however their utility in viral metagenomics is limited. HoloVir is a robust and flexible data analysis pipeline that provides an optimized and validated workflow for taxonomic and functional characterization of viral metagenomes derived from invertebrate holobionts. Simulated viral metagenomes comprising varying levels of viral diversity and abundance were used to determine the optimal assembly and gene prediction strategy, and multiple sequence assembly methods and gene prediction tools were tested in order to optimize our analysis workflow. HoloVir performs pairwise comparisons of single read and predicted gene datasets against the viral RefSeq database to assign taxonomy and additional comparison to phage-specific and cellular markers is undertaken to support the taxonomic assignments and identify potential cellular contamination. Broad functional classification of the predicted genes is provided by assignment of COG microbial functional category classifications using EggNOG and higher resolution functional analysis is achieved by searching for enrichment of specific Swiss-Prot keywords within the viral metagenome. Application of HoloVir to viral metagenomes from the coral Pocillopora damicornis and the sponge Rhopaloeides odorabile demonstrated that HoloVir provides a valuable tool to characterize holobiont viral communities across species, environments, or experiments. PMID- 27375565 TI - Cocaine Enhances HIV-1 Transcription in Macrophages by Inducing p38 MAPK Phosphorylation. AB - Cocaine is a commonly used illicit drug among HIV-1 infected individuals and is known to increase HIV-1 replication in permissive cells including PBMCs, CD4(+) T cells, and macrophages. Cocaine's potentiating effects on HIV-1 replication in macrophages- the primary targets of the virus in the central nervous system, has been suggested to play an important role in HIV-1 neuro-pathogenesis. However, the mechanism by which cocaine enhances HIV-1 replication in macrophages remain poorly understood. Here, we report the identification of cocaine-induced signaling events that lead to enhanced HIV-1 transcription in macrophages. Treatment of physiologically relevant concentrations of cocaine enhanced HIV-1 transcription in a dose-dependent manner in infected THP-1 monocyte-derived macrophages (THP-1macs) and primary monocyte-derived macrophages (MDMs). Toward decoding the underlying mechanism, results presented in this report demonstrate that cocaine induces the phosphorylation of p38 mitogen activated protein kinase (p38 MAPK), a known activator of HIV-1 transcription. We also present data suggesting that the p38 MAPK-driven HIV-1 transcription is dependent on the induction of mitogen- and stress-activated protein kinase 1 (MSK1). Consequently, MSK1 mediates the phosphorylation of serine 10 residue of histone 3 (H3 Ser10), which is known to activate transcription of genes including that of HIV-1 in macrophages. Importantly, our results show that inhibition of p38 MAPK/MSK1 signaling by specific pharmacological inhibitors abrogated the positive effect of cocaine on HIV-1 transcription. These results validate the functional link between cocaine and p38 MAPK/MSK1 pathways. Together, our results demonstrate for the first time that the p38 MAPK/MSK1 signaling pathway plays a critical role in the cocaine-induced potentiating effects on HIV-1 infection, thus providing new insights into the interplay between cocaine abuse and HIV-1 neuro-pathogenesis. PMID- 27375566 TI - Bacteriophages as Weapons Against Bacterial Biofilms in the Food Industry. AB - Microbiological contamination in the food industry is often attributed to the presence of biofilms in processing plants. Bacterial biofilms are complex communities of bacteria attached to a surface and surrounded by an extracellular polymeric material. Their extreme resistance to cleaning and disinfecting processes is related to a unique organization, which implies a differential bacterial growth and gene expression inside the biofilm. The impact of biofilms on health, and the economic consequences, has promoted the development of different approaches to control or remove biofilm formation. Recently, successful results in phage therapy have boosted new research in bacteriophages and phage lytic proteins for biofilm eradication. In this regard, this review examines the environmental factors that determine biofilm development in food-processing equipment. In addition, future perspectives for the use of bacteriophage-derived tools as disinfectants are discussed. PMID- 27375567 TI - Indole-3-Acetic Acid Is Produced by Emiliania huxleyi Coccolith-Bearing Cells and Triggers a Physiological Response in Bald Cells. AB - Indole-3-acetic acid (IAA) is an auxin produced by terrestrial plants which influences development through a variety of cellular mechanisms, such as altering cell orientation, organ development, fertility, and cell elongation. IAA is also produced by bacterial pathogens and symbionts of plants and algae, allowing them to manipulate growth and development of their host. They do so by either producing excess exogenous IAA or hijacking the IAA biosynthesis pathway of their host. The endogenous production of IAA by algae remains contentious. Using Emiliania huxleyi, a globally abundant marine haptophyte, we investigated the presence and potential role of IAA in algae. Homologs of genes involved in several tryptophan-dependent IAA biosynthesis pathways were identified in E. huxleyi. This suggests that this haptophyte can synthesize IAA using various precursors derived from tryptophan. Addition of L-tryptophan to E. huxleyi stimulated IAA production, which could be detected using Salkowski's reagent and GC * GC-TOFMS in the C cell type (coccolith bearing), but not in the N cell type (bald). Various concentrations of IAA were exogenously added to these two cell types to identify a physiological response in E. huxleyi. The N cell type, which did not produce IAA, was more sensitive to it, showing an increased variation in cell size, membrane permeability, and a corresponding increase in the photosynthetic potential quantum yield of Photosystem II (PSII). A roseobacter (bacteria commonly associated with E. huxleyi) Ruegeria sp. R11, previously shown to produce IAA, was co-cultured with E. huxleyi C and N cells. IAA could not be detected from these co-cultures, and even when stimulated by addition of L tryptophan, they produced less IAA than axenic C type culture similarly induced. This suggests that IAA plays a novel role signaling between different E. huxleyi cell types, rather than between a bacteria and its algal host. PMID- 27375568 TI - Comparative Genomics of Iron-Transporting Systems in Bacillus cereus Strains and Impact of Iron Sources on Growth and Biofilm Formation. AB - Iron is an important element for bacterial viability, however it is not readily available in most environments. We studied the ability of 20 undomesticated food isolates of Bacillus cereus and two reference strains for capacity to use different (complex) iron sources for growth and biofilm formation. Studies were performed in media containing the iron scavenger 2,2-Bipyridine. Transcriptome analysis using B. cereus ATCC 10987 indeed showed upregulation of predicted iron transporters in the presence of 2,2-Bipyridine, confirming that iron was depleted upon its addition. Next, the impact of iron sources on growth performance of the 22 strains was assessed and correlations between growth stimulation and presence of putative iron transporter systems in the genome sequences were analyzed. All 22 strains effectively used Fe citrate and FeCl3 for growth, and possessed genes for biosynthesis of the siderophore bacillibactin, whereas seven strains lacked genes for synthesis of petrobactin. Hemoglobin could be used by all strains with the exception of one strain that lacked functional petrobactin and IlsA systems. Hemin could be used by the majority of the tested strains (19 of 22). Notably, transferrin, ferritin, and lactoferrin were not commonly used by B. cereus for growth, as these iron sources could be used by 6, 3, and 2 strains, respectively. Furthermore, biofilm formation was found to be affected by the type of iron source used, including stimulation of biofilms at liquid-air interphase (FeCl3 and Fe citrate) and formation of submerged type biofilms (hemin and lactoferrin). Our results show strain variability in the genome-encoded repertoire of iron transporting systems and differences in efficacy to use complex iron sources for growth and biofilm formation. These features may affect B. cereus survival and persistence in specific niches. PMID- 27375569 TI - Cytomegalovirus-Infected Cells Resist T Cell Mediated Killing in an HLA Recognition Independent Manner. AB - In order to explore the potential of HLA-independent T cell therapy for human cytomegalovirus (HCMV) infections, we developed a chimeric antigen receptor (CAR) directed against the HCMV encoded glycoprotein B (gB), which is expressed at high levels on the surface of infected cells. T cells engineered with this anti-gB CAR recognized HCMV-infected cells and released cytokines and cytotoxic granules. Unexpectedly, and in contrast to analogous approaches for HIV, Hepatitis B or Hepatitis C virus, we found that HCMV-infected cells were resistant to killing by the CAR-modified T cells. In order to elucidate whether this phenomenon was restricted to the use of CARs, we extended our experiments to T cell receptor (TCR)-mediated recognition of infected cells. To this end we infected fibroblasts with HCMV-strains deficient in viral inhibitors of antigenic peptide presentation and targeted these HLA-class I expressing peptide-loaded infected cells with peptide-specific cytotoxic T cells (CTLs). Despite strong degranulation and cytokine production by the T cells, we again found significant inhibition of lysis of HCMV-infected cells. Impairment of cell lysis became detectable 1 day after HCMV infection and gradually increased during the following 3 days. We thus postulate that viral anti-apoptotic factors, known to inhibit suicide of infected host cells, have evolved additional functions to directly abrogate T cell cytotoxicity. In line with this hypothesis, CAR-T cell cytotoxicity was strongly inhibited in non-infected fibroblasts by expression of the HCMV-protein UL37x1, and even more so by additional expression of UL36. Our data extend the current knowledge on Betaherpesviral evasion from T cell immunity and show for the first time that, beyond impaired antigen presentation, infected cells are efficiently protected by direct blockade of cytotoxic effector functions through viral proteins. PMID- 27375570 TI - Development and Identification of a Novel Anti-HIV-1 Peptide Derived by Modification of the N-Terminal Domain of HIV-1 Integrase. AB - The viral enzyme integrase (IN) is essential for the replication of human immunodeficiency virus type 1 (HIV-1) and represents an important target for the development of new antiretroviral drugs. In this study, we focused on the N terminal domain (NTD), which is mainly involved into protein oligomerization process, for the development and synthesis of a library of overlapping peptide sequences, with specific length and specific offset covering the entire native protein sequence NTD IN 1-50. The most potent fragment, VVAKEIVAH (peptide 18), which includes a His residue instead of the natural Ser at position 39, inhibits the HIV-1 IN activity with an IC50 value of 4.5 MUM. Amino acid substitution analysis on this peptide revealed essential residues for activity and allowed us to identify two nonapeptides (peptides 24 and 25), that show a potency of inhibition similar to the one of peptide 18. Interestingly, peptide 18 does not interfere with the dynamic interplay between IN subunits, while peptides 24 and 25 modulated these interactions in different manners. In fact, peptide 24 inhibited the IN-IN dimerization, while peptide 25 promoted IN multimerization, with IC50 values of 32 and 4.8 MUM, respectively. In addition, peptide 25 has shown to have selective anti-infective cell activity for HIV-1. These results confirmed peptide 25 as a hit for further development of new chemotherapeutic agents against HIV-1. PMID- 27375571 TI - Fungal and Prokaryotic Activities in the Marine Subsurface Biosphere at Peru Margin and Canterbury Basin Inferred from RNA-Based Analyses and Microscopy. AB - The deep sedimentary biosphere, extending 100s of meters below the seafloor harbors unexpected diversity of Bacteria, Archaea, and microbial eukaryotes. Far less is known about microbial eukaryotes in subsurface habitats, albeit several studies have indicated that fungi dominate microbial eukaryotic communities and fungal molecular signatures (of both yeasts and filamentous forms) have been detected in samples as deep as 1740 mbsf. Here, we compare and contrast fungal ribosomal RNA gene signatures and whole community metatranscriptomes present in sediment core samples from 6 and 95 mbsf from Peru Margin site 1229A and from samples from 12 and 345 mbsf from Canterbury Basin site U1352. The metatranscriptome analyses reveal higher relative expression of amino acid and peptide transporters in the less nutrient rich Canterbury Basin sediments compared to the nutrient rich Peru Margin, and higher expression of motility genes in the Peru Margin samples. Higher expression of genes associated with metals transporters and antibiotic resistance and production was detected in Canterbury Basin sediments. A poly-A focused metatranscriptome produced for the Canterbury Basin sample from 345 mbsf provides further evidence for active fungal communities in the subsurface in the form of fungal-associated transcripts for metabolic and cellular processes, cell and membrane functions, and catalytic activities. Fungal communities at comparable depths at the two geographically separated locations appear dominated by distinct taxa. Differences in taxonomic composition and expression of genes associated with particular metabolic activities may be a function of sediment organic content as well as oceanic province. Microscopic analysis of Canterbury Basin sediment samples from 4 and 403 mbsf produced visualizations of septate fungal filaments, branching fungi, conidiogenesis, and spores. These images provide another important line of evidence supporting the occurrence and activity of fungi in the deep subseafloor biosphere. PMID- 27375572 TI - Inactivation of Acinetobacter baumannii Biofilms on Polystyrene, Stainless Steel, and Urinary Catheters by Octenidine Dihydrochloride. AB - Acinetobacter baumannii is a major nosocomial pathogen causing human infections with significant mortality rates. In most cases, infections are acquired through exposure to A. baumannii biofilms that persist on contaminated hospital equipment and surfaces. Thus, it is imperative to develop effective measures for controlling A. baumannii biofilms in nosocomial settings. This study investigated the efficacy of octenidine dihydrochloride (OH), a new generation disinfectant for reducing A. baumannii biofilms on polystyrene, stainless steel and catheters. OH at 0.3% (5 mM), 0.6% (10 mM), and 0.9% (15 mM) was effective in significantly inactivating A. baumannii biofilms on all tested surfaces (P < 0.05). Furthermore, OH was equally effective in inactivating biofilms of multidrug resistant and drug susceptible A. baumannii isolates. In addition, confocal imaging revealed the predominance of dead cells in the OH-treated samples in comparison to the control. Further, scanning electron microscopy of biofilms formed on catheters revealed that OH treatment significantly reduced A. baumannii biofilm populations in corroboration with our antibiofilm assay. These data underscore the efficacy of OH in inactivating A. baumannii biofilms, thereby suggesting its potential use as a disinfectant or a catheter lock solution to control A. baumannii infections. PMID- 27375573 TI - Klebsiella pneumoniae Asparagine tDNAs Are Integration Hotspots for Different Genomic Islands Encoding Microcin E492 Production Determinants and Other Putative Virulence Factors Present in Hypervirulent Strains. AB - Due to the developing of multi-resistant and invasive hypervirulent strains, Klebsiella pneumoniae has become one of the most urgent bacterial pathogen threats in the last years. Genomic comparison of a growing number of sequenced isolates has allowed the identification of putative virulence factors, proposed to be acquirable mainly through horizontal gene transfer. In particular, those related with synthesizing the antibacterial peptide microcin E492 (MccE492) and salmochelin siderophores were found to be highly prevalent among hypervirulent strains. The determinants for the production of both molecules were first reported as part of a 13-kbp segment of K. pneumoniae RYC492 chromosome, and were cloned and characterized in E. coli. However, the genomic context of this segment in K. pneumoniae remained uncharacterized. In this work, we provided experimental and bioinformatics evidence indicating that the MccE492 cluster is part of a highly conserved 23-kbp genomic island (GI) named GIE492, that was integrated in a specific asparagine-tRNA gene (asn-tDNA) and was found in a high proportion of isolates from liver abscesses sampled around the world. This element resulted to be unstable and its excision frequency increased after treating bacteria with mitomycin C and upon the overexpression of the island-encoded integrase. Besides the MccE492 genetic cluster, it invariably included an integrase-coding gene, at least seven protein-coding genes of unknown function, and a putative transfer origin that possibly allows this GI to be mobilized through conjugation. In addition, we analyzed the asn-tDNA loci of all the available K. pneumoniae assembled chromosomes to evaluate them as GI-integration sites. Remarkably, 73% of the strains harbored at least one GI integrated in one of the four asn-tDNA present in this species, confirming them as integration hotspots. Each of these tDNAs was occupied with different frequencies, although they were 100% identical. Also, we identified a total of 47 asn-tDNA-associated GIs that were classified into 12 groups of homology differing in theencoded functionalities but sharing with GIE492 a conserved recombination module and potentially its mobility features. Most of these GIs encoded factors with proven or potential role in pathogenesis, constituting a major reservoir of virulence factors in this species. PMID- 27375574 TI - Genomic and Metagenomic Analysis of Diversity-Generating Retroelements Associated with Treponema denticola. AB - Diversity-generating retroelements (DGRs) are genetic cassettes that can produce massive protein sequence variation in prokaryotes. Presumably DGRs confer selective advantages to their hosts (bacteria or viruses) by generating variants of target genes-typically resulting in target proteins with altered ligand binding specificity-through a specialized error-prone reverse transcription process. The only extensively studied DGR system is from the Bordetella phage BPP 1, although DGRs are predicted to exist in other species. Using bioinformatics analysis, we discovered that the DGR system associated with the Treponema denticola species (a human oral-associated periopathogen) is dynamic (with gains/losses of the system found in the isolates) and diverse (with multiple types found in isolated genomes and the human microbiota). The T. denticola DGR is found in only nine of the 17 sequenced T. denticola strains. Analysis of the DGR-associated template regions and reverse transcriptase gene sequences revealed two types of DGR systems in T. denticola: the ATCC35405-type shared by seven isolates including ATCC35405; and the SP32-type shared by two isolates (SP32 and SP33), suggesting multiple DGR acquisitions. We detected additional variants of the T. denticola DGR systems in the human microbiomes, and found that the SP32 type DGR is more abundant than the ATCC35405-type in the healthy human oral microbiome, although the latter is found in more sequenced isolates. This is the first comprehensive study to characterize the DGRs associated with T. denticola in individual genomes as well as human microbiomes, demonstrating the importance of utilizing both individual genomes and metagenomes for characterizing the elements, and for analyzing their diversity and distribution in human populations. PMID- 27375575 TI - Bacterial Dormancy Is More Prevalent in Freshwater than Hypersaline Lakes. AB - Bacteria employ a diverse array of strategies to survive under extreme environmental conditions but maintaining these adaptations comes at an energetic cost. If energy reserves drop too low, extremophiles may enter a dormant state to persist. We estimated bacterial dormancy and identified the environmental variables influencing our activity proxy in 10 hypersaline and freshwater lakes across the Western United States. Using ribosomal RNA:DNA ratios as an indicator for bacterial activity, we found that the proportion of the community exhibiting dormancy was 16% lower in hypersaline than freshwater lakes. Based on our indicator variable multiple regression results, saltier conditions in both freshwater and hypersaline lakes increased activity, suggesting that salinity was a robust environmental filter structuring bacterial activity in lake ecosystems. To a lesser degree, higher total phosphorus concentrations reduced dormancy in all lakes. Thus, even under extreme conditions, the competition for resources exerted pressure on activity. Within the compositionally distinct and less diverse hypersaline communities, abundant taxa were disproportionately active and localized in families Microbacteriaceae (Actinobacteria), Nitriliruptoraceae (Actinobacteria), and Rhodobacteraceae (Alphaproteobacteria). Our results are consistent with the view that hypersaline communities are able to capitalize on a seemingly more extreme, yet highly selective, set of conditions and finds that extremophiles may need dormancy less often to thrive and survive. PMID- 27375576 TI - Population Dynamics and Community Composition of Ammonia Oxidizers in Salt Marshes after the Deepwater Horizon Oil Spill. AB - The recent oil spill in the Gulf of Mexico had significant effects on microbial communities in the Gulf, but impacts on nitrifying communities in adjacent salt marshes have not been investigated. We studied persistent effects of oil on ammonia-oxidizing archaeal (AOA) and bacterial (AOB) communities and their relationship to nitrification rates and soil properties in Louisiana marshes impacted by the Deepwater Horizon oil spill. Soils were collected at oiled and unoiled sites from Louisiana coastal marshes in July 2012, 2 years after the spill, and analyzed for community differences based on ammonia monooxygenase genes (amoA). Terminal Restriction Fragment Polymorphism and DNA sequence analyses revealed significantly different AOA and AOB communities between the three regions, but few differences were found between oiled and unoiled sites. Community composition of nitrifiers was best explained by differences in soil moisture and nitrogen content. Despite the lack of significant oil effects on overall community composition, we identified differences in correlations of individual populations with potential nitrification rates between oiled and unoiled sites that help explain previously published correlation patterns. Our results suggest that exposure to oil, even 2 years post-spill, led to subtle changes in population dynamics. How, or if, these changes may impact ecosystem function in the marshes, however, remains uncertain. PMID- 27375577 TI - Prevention and Control of Antimicrobial Resistant Healthcare-Associated Infections: The Microbiology Laboratory Rocks! AB - In Europe, each year, more than four milion patients acquire a healthcare associated infection (HAI) and almost 40 thousand die as a direct consequence of it. Regardless of many stategies to prevent and control HAIs, they remain an important cause of morbidity and mortality worldwide with a significant economic impact: a recent estimate places it at the ten billion dollars/year. The control of HAIs requires a prompt and efficient identification of the etiological agent and a rapid communication with the clinician. The Microbiology Laboratory has a significant role in the prevention and control of these infections and is a key element of any Infection Control Program. The work of the Microbiology Laboratory covers microbial isolation and identification, determination of antimicrobial susceptibility patterns, epidemiological surveillance and outbreak detection, education, and report of quality assured results. In this paper we address the role and importance of the Microbiology Laboratory in the prevention and control of HAI and in Antibiotic Stewardship Programs and how it can be leveraged when combined with the use of information systems. Additionally, we critically review some challenges that the Microbiology Laboratory has to deal with, including the selection of analytic methods and the proper use of communication channels with other healthcare services. PMID- 27375578 TI - Biofilm Matrix Composition Affects the Susceptibility of Food Associated Staphylococci to Cleaning and Disinfection Agents. AB - Staphylococci are frequently isolated from food processing environments, and it has been speculated whether survival after cleaning and disinfection with benzalkonium chloride (BC)-containing disinfectants is due to biofilm formation, matrix composition, or BC efflux mechanisms. Out of 35 food associated staphylococci, eight produced biofilm in a microtiter plate assay and were identified as Staphylococcus capitis (2), S. cohnii, S. epidermidis, S. lentus (2), and S. saprophyticus (2). The eight biofilm producing strains were characterized using whole genome sequencing. Three of these strains contained the ica operon responsible for production of a polysaccharide matrix, and formed a biofilm which was detached upon exposure to the polysaccharide degrading enzyme Dispersin B, but not Proteinase K or trypsin. These strains were more tolerant to the lethal effect of BC both in suspension and biofilm than the remaining five biofilm producing strains. The five BC susceptible strains were characterized by lack of the ica operon, and their biofilms were detached by Proteinase K or trypsin, but not Dispersin B, indicating that proteins were major structural components of their biofilm matrix. Several novel cell wall anchored repeat domain proteins with domain structures similar to that of MSCRAMM adhesins were identified in the genomes of these strains, potentially representing novel mechanisms of ica-independent biofilm accumulation. Biofilms from all strains showed similar levels of detachment after exposure to alkaline chlorine, which is used for cleaning in the food industry. Strains with qac genes encoding BC efflux pumps could grow at higher concentrations of BC than strains without these genes, but no differences were observed at biocidal concentrations. In conclusion, the biofilm matrix of food associated staphylococci varies with respect to protein or polysaccharide nature, and this may affect the sensitivity toward a commonly used disinfectant. PMID- 27375579 TI - Sub-Cellular Localization and Complex Formation by Aminoacyl-tRNA Synthetases in Cyanobacteria: Evidence for Interaction of Membrane-Anchored ValRS with ATP Synthase. AB - tRNAs are charged with cognate amino acids by aminoacyl-tRNA synthetases (aaRSs) and subsequently delivered to the ribosome to be used as substrates for gene translation. Whether aminoacyl-tRNAs are channeled to the ribosome by transit within translational complexes that avoid their diffusion in the cytoplasm is a matter of intense investigation in organisms of the three domains of life. In the cyanobacterium Anabaena sp. PCC 7120, the valyl-tRNA synthetase (ValRS) is anchored to thylakoid membranes by means of the CAAD domain. We have investigated whether in this organism ValRS could act as a hub for the nucleation of a translational complex by attracting other aaRSs to the membranes. Out of the 20 aaRSs, only ValRS was found to localize in thylakoid membranes whereas the other enzymes occupied the soluble portion of the cytoplasm. To investigate the basis for this asymmetric distribution of aaRSs, a global search for proteins interacting with the 20 aaRSs was conducted. The interaction between ValRS and the FoF1 ATP synthase complex here reported is of utmost interest and suggests a functional link between elements of the gene translation and energy production machineries. PMID- 27375580 TI - A High Throughput Assay for Screening Host Restriction Factors and Antivirals Targeting Influenza A Virus. AB - Influenza A virus (IAV) is a human respiratory pathogen that causes seasonal epidemics and occasional global pandemics with devastating levels of morbidity and mortality. Currently approved treatments against influenza are losing effectiveness, as new viral strains are often refractory to conventional treatments. Thus, there is an urgent need to find new therapeutic targets with which to develop novel antiviral drugs. The common strategy to discover new drug targets and antivirals is high throughput screening. However, most current screenings for IAV rely on the engineered virus carrying a reporter, which prevents the application to newly emerging wild type flu viruses, such as 2009 pandemic H1N1 flu. Here we developed a simple and sensitive screening assay for wild type IAV by quantitatively analyzing viral protein levels using a Dot Blot Assay in combination with the LI-COR Imaging System (DBALIS). We first validated DBALIS in overexpression and RNAi assays, which are suitable methods for screening host factors regulating viral infection. More importantly, we also validated and initiated drug screening using DBALIS. A pilot compound screening identified a small molecule that inhibited IAV infection. Taken together, our method represents a reliable and convenient high throughput assay for screening novel host factors and antiviral compounds. PMID- 27375582 TI - Editorial: Current Challenges and Future Perspectives on Emerging Bioelectrochemical Technologies. PMID- 27375581 TI - Identification and Characterization of Novel Small RNAs in Rickettsia prowazekii. AB - Emerging evidence implicates a critically important role for bacterial small RNAs (sRNAs) as post-transcriptional regulators of physiology, metabolism, stress/adaptive responses, and virulence, but the roles of sRNAs in pathogenic Rickettsia species remain poorly understood. Here, we report on the identification of both novel and well-known bacterial sRNAs in Rickettsia prowazekii, known to cause epidemic typhus in humans. RNA sequencing of human microvascular endothelial cells (HMECs), the preferred targets during human rickettsioses, infected with R. prowazekii revealed the presence of 35 trans acting and 23 cis-acting sRNAs, respectively. Of these, expression of two trans acting (Rp_sR17 and Rp_sR60) and one cis-acting (Rp_sR47) novel sRNAs and four well-characterized bacterial sRNAs (RNaseP_bact_a, alpha-tmRNA, 4.5S RNA, 6S RNA) was further confirmed by Northern blot or RT-PCR analyses. The transcriptional start sites of five novel rickettsial sRNAs and 6S RNA were next determined using 5' RLM-RACE yielding evidence for their independent biogenesis in R. prowazekii. Finally, computational approaches were employed to determine the secondary structures and potential mRNA targets of novel sRNAs. Together, these results establish the presence and expression of sRNAs in R. prowazekii during host cell infection and suggest potential functional roles for these important post transcriptional regulators in rickettsial biology and pathogenesis. PMID- 27375583 TI - Combinatorial Effects of Aromatic 1,3-Disubstituted Ureas and Fluoride on In vitro Inhibition of Streptococcus mutans Biofilm Formation. AB - Dental caries occur as a result of disequilibrium between acid producing pathogenic bacteria and alkali generating commensal bacteria within a dental biofilm (dental plaque). Streptococcus mutans has been reported as a primary cariogenic pathogen associated with dental caries. Emergence of multidrug resistant as well as fluoride resistant strains of S. mutans due to over use of various antibiotics are a rising problem and prompted the researchers worldwide to search for alternative therapies. In this perspective, the present study was aimed to screen selective inhibitors against ComA, a bacteriocin associated ABC transporter, involved in the quorum sensing of S. mutans. In light of our present in silico findings, 1,3-disubstituted urea derivatives which had better affinity to ComA were chemically synthesized in the present study for in vitro evaluation of S. mutans biofilm inhibition. The results revealed that 1,3-disubstituted urea derivatives showed good biofilm inhibition. In addition, synthesized compounds exhibited potent synergy with a very low concentration of fluoride (31.25-62.5 ppm) in inhibiting the biofilm formation of S. mutans without affecting the bacterial growth. Further, the results were supported by confocal laser scanning microscopy. On the whole, from our experimental results we conclude that the combinatorial application of fluoride and disubstituted ureas has a potential synergistic effect which has a promising approach in combating multidrug resistant and fluoride resistant S. mutans in dental caries management. PMID- 27375584 TI - Use of Potential Probiotic Lactic Acid Bacteria (LAB) Biofilms for the Control of Listeria monocytogenes, Salmonella Typhimurium, and Escherichia coli O157:H7 Biofilms Formation. AB - Use of probiotic biofilms can be an alternative approach for reducing the formation of pathogenic biofilms in food industries. The aims of this study were (i) to evaluate the probiotic properties of bacteriocinogenic (Lactococcus lactis VB69, L. lactis VB94, Lactobacillus sakei MBSa1, and Lactobacillus curvatus MBSa3) and non-bacteriocinogenic (L. lactis 368, Lactobacillus helveticus 354, Lactobacillus casei 40, and Weissela viridescens 113) lactic acid bacteria (LAB) isolated from Brazilian's foods and (ii) to develop protective biofilms with these strains and test them for exclusion of Listeria monocytogenes, Escherichia coli O157:H7, and Salmonella Typhimurium. LAB were tested for survival in acid and bile salt conditions, surface properties, biosurfactant production, beta galactosidase and gelatinase activity, antibiotic resistance and presence of virulence genes. Most strains survived exposure to pH 2 and 4% bile salts. The highest percentages of auto-aggregation were obtained after 24 h of incubation. Sixty-seven percentage auto-aggregation value was observed in W. viridescens 113 and Lactobacillus curvatus MBSa3 exhibited the highest co-aggregation (69% with Listeria monocytogenes and 74.6% with E. coli O157:H7), while the lowest co aggregation was exhibited by W. viridescens 113 (53.4% with Listeria monocytogenes and 38% with E. coli O157:H7). Tests for hemolytic activity, bacterial cell adherence with xylene, and drop collapse confirmed the biosurfactant-producing ability of most strains. Only one strain (L. lactis 368) produced beta-galactosidase. All strains were negative for virulence genes cob, ccf, cylLL, cylLs, cyllM, cylB, cylA and efaAfs and gelatinase production. The antibiotic susceptibility tests indicated that the MIC for ciprofloxacin, clindamycin, gentamicin, kanamycin, and streptomycin did not exceed the epidemiological cut-off suggested by the European Food Safety Authority. Some strains were resistant to one or more antibiotics and resistance to antibiotics was species and strain dependent. In the protective biofilm assays, strains L. lactis 368 (bac-), Lactobacillus curvatus MBSa3 (bac+), and Lactobacillus sakei MBSa1 (bac+) resulted in more than six log reductions in the pathogens counts when compared to the controls. This effect could not be attributed to bacteriocin production. These results suggest that these potential probiotic strains can be used as alternatives for control of biofilm formation by pathogenic bacteria in the food industry, without conferring a risk to the consumers. PMID- 27375585 TI - Anti-viral Effect of Bifidobacterium adolescentis against Noroviruses. AB - This study aims to investigate the effect of Bifidobacterium adolescentis against noroviruses (NoVs). Murine norovirus-1 (MNV-1) used as a surrogate was detected by plaque assay and RT-qPCR. Human NoV virus like particles (VLPs) were detected by cell-binding assay. It was shown that the presence of B. adolescentis could inhibit the multiplication of MNV-1 on RAW 264.7 cells within 48 h of co incubation period at 37 degrees C. This inhibition did not occur at the viral binding stage, as no difference was observed in MNV-1 genomic copies collected from washed RAW 264.7 cells without and with B. adolescentis after co-incubation for 1 h at room temperature. Meanwhile, the presence of B. adolescentis decreased the binding of human NoV GI.1 VLPs to both Caco-2 cells and HT-29 cells, while no reduction was induced for the binding of human NoV GII.4 VLPs to Caco-2 cells. PMID- 27375586 TI - Enterocyte-Associated Microbiome of the Hadza Hunter-Gatherers. AB - By means of a recently developed non-invasive ex vivo minimal model based on the interaction of the human enterocyte-like HT29 cell line and fecal slurries, we explored the enterocyte-associated microbiome of 21 Hadza hunter-gatherers and nine urban living Italians. Though reductionist, this model allows inferring the microbiota structural and functional arrangement as it interacts with enterocytes. Microbial suspensions obtained from Hadza or Italian stools were first evaluated for structural integrity by high resolution-scanning electron microscopy and co-incubated with HT29 cell monolayers. The enterocyte adherent microbiota fraction was then characterized by 16S rRNA gene sequencing and predictive functional profiling using PICRUSt. Compared to Italians, the Hadza enterocyte-associated microbiome was characterized by a greater amount of adhesive microorganisms with pathogenic potential, such as Proteobacteria, Erysipelotrichaceae, Enterococcus, Clostridium and Sarcina. These compositional characteristics were reflected in a functional enrichment in membrane transport, signal transduction, signaling molecules and interaction. Our results depict a new interesting mutualistic configuration of the enterocyte-associated microbiome in Hadza, stressing the importance of microbe-host interaction at the mucosal surface along the course of human evolution. PMID- 27375587 TI - Antimicrobial-Resistant Escherichia coli Survived in Dust Samples for More than 20 Years. AB - In a retrospective study, 119 sedimentation dust samples stored between five and 35 years from various barns of intensive livestock farming were evaluated for the occurrence of cultivatable Escherichia coli. Growth of E. coli occurred in 54 samples. Successful cultivation was achieved in samples from as early as 1994. The frequency of detection increased from earlier to later time periods, but the concentrations, which ranged between 3.4 * 10(2) and 1.1 * 10(5) colony-forming units per gram, did not correlate with sample age (Spearman rank correlation; p > 0.05). We hypothesize that E. coli cells survived in dust samples without cell division because of the storage conditions. Dry material (dust) with low water activities (arithmetic mean < 0.6) and storage at 4 degrees C in the dark likely facilitated long-term survival. E. coli were isolated on MacConkey agar with and without ciprofloxacin supplementation. For 110 isolates (79 from non-supplemented media and 31 from supplemented media), we determined the E. coli phylotype and antimicrobial resistance. Six phylogenetic groups were identified. Phylogroups A and B1 predominated. Compared to group A, phylogroup B1 was significantly associated with growth on ciprofloxacin-supplemented media (chi-square test, p = 0.003). Furthermore, the antibiotic resistance profiles determined by a microdilution method revealed that isolates were phenotypically resistant to at least one antimicrobial substance and that more than 50% were resistant to a minimum of five out of 10 antibiotics tested. A linear mixed model was used to identify factors associated with the number of phenotypic resistances of individual isolates. Younger isolates and isolates from fattening poultry barns tended to be resistant to significantly more antibiotics than older isolates and those from laying-hen houses (p = 0.01 and p = 0.02, respectively). Sample origin and storage conditions may have influenced the number of antimicrobial resistances. Overall, we found that under particular conditions, dust from farm animal houses can be reservoirs for antimicrobial-resistant E. coli for at least 20 years. The survival strategies that allow E. coli to survive such long periods in environmental samples are not fully understood and could be an interesting research topic for future studies. PMID- 27375588 TI - Deciphering Staphylococcus sciuri SAT-17 Mediated Anti-oxidative Defense Mechanisms and Growth Modulations in Salt Stressed Maize (Zea mays L.). AB - Soil salinity severely affects plant nutrient use efficiency and is a worldwide constraint for sustainable crop production. Plant growth-promoting rhizobacteria, with inherent salinity tolerance, are able to enhance plant growth and productivity by inducing modulations in various metabolic pathways. In the present study, we reported the isolation and characterization of a salt-tolerant rhizobacterium from Kallar grass [Leptochloa fusca (L.) Kunth]. Sequencing of the 16S rRNA gene revealed its lineage to Staphylococcus sciuri and it was named as SAT-17. The strain exhibited substantial potential of phosphate solubilization as well as indole-3-acetic acid production (up to 2 M NaCl) and 1-aminocyclopropane 1-carboxylic acid deaminase activity (up to 1.5 M NaCl). Inoculation of a rifampicin-resistant derivative of the SAT-17 with maize, in the absence of salt stress, induced a significant increase in plant biomass together with decreased reactive oxygen species and increased activity of cellular antioxidant enzymes. The derivative strain also significantly accumulated nutrients in roots and shoots, and enhanced chlorophyll and protein contents in comparison with non inoculated plants. Similar positive effects were observed in the presence of salt stress, although the effect was more prominent at 75 mM in comparison to higher NaCl level (150 mM). The strain survived in the rhizosphere up to 30 days at an optimal population density (ca. 1 * 10(6) CFU mL(-1)). It was concluded that S. sciuri strain SAT-17 alleviated maize plants from salt-induced cellular oxidative damage and enhanced growth. Further field experiments should be conducted, considering SAT-17 as a potential bio-fertilizer, to draw parallels between PGPR inoculation, elemental mobility patterns, crop growth and productivity in salt stressed semi-arid and arid regions. PMID- 27375589 TI - Effect of a Ropy Exopolysaccharide-Producing Bifidobacterium animalis subsp. lactis Strain Orally Administered on DSS-Induced Colitis Mice Model. AB - Exopolysaccharide (EPS)-producing bifidobacteria, particularly Bifidobacterium animalis subsp. lactis strains, are used in the functional food industry as promising probiotics with purported beneficial effects. We used three isogenic strains of B. animalis subsp. lactis, with different EPS producing phenotypes (mucoid-ropy and non-ropy), in order to determine their capability to survive the murine gastrointestinal tract transit, as well as to evaluate their role in improving clinical outcomes in a chemically-induced colitis model. The three strains were able to survive in the intestinal tract of C57BL/6J mice during the course of the intervention study. Furthermore, the disease activity index (DAI) of the animal group treated with the ropy strain was significantly lower than of the DAI of the placebo group at the end of the treatment. However, no significant differences were found among the three strains. The analysis of several immune parameters, such as TNFalpha and IL-10 quantified in blood plasma and lymphocyte populations enumerated in mesenteric nodes, showed some significant variations among the four experimental animal groups. Remarkably, a higher capability of the ropy strain to increase regulatory T-cells in mesenteric lymphoid nodes was demonstrated, suggesting a higher ability of this strain to regulate inflammatory responses at mucosal level. Our data indicate that strains of B. animalis subsp. lactis producing EPS that confer a mucoid-ropy phenotype could represent promising candidates to perform further studies targeting intestinal inflammatory processes. PMID- 27375591 TI - Corrigendum: A flexible and economical barcoding approach for highly multiplexed amplicon sequencing of diverse target genes. AB - [This corrects the article on p. 731 in vol. 6, PMID: 26236305.]. PMID- 27375590 TI - Herpesvirus Late Gene Expression: A Viral-Specific Pre-initiation Complex Is Key. AB - During their productive cycle, herpesviruses exhibit a strictly regulated temporal cascade of gene expression that can be divided into three general stages: immediate-early (IE), early (E), and late (L). This expression program is the result of a complex interplay between viral and cellular factors at both the transcriptional and post-transcriptional levels, as well as structural differences within the promoter architecture for each of the three gene classes. Since the cellular enzyme RNA polymerase II (RNAP-II) is responsible for the transcription of herpesvirus genes, most viral promoters contain DNA motifs that are common with those of cellular genes, although promoter complexity decreases from immediate-early to late genes. Immediate-early and early promoters contain numerous cellular and viral cis-regulating sequences upstream of a TATA box, whereas late promoters differ significantly in that they lack cis-acting sequences upstream of the transcription start site (TSS). Moreover, in the case of the beta- and gamma-herpesviruses, a TATT box motif is frequently found in the position where the consensus TATA box of eukaryotic promoters usually localizes. The mechanisms of transcriptional regulation of the late viral gene promoters appear to be different between alpha-herpesviruses and the two other herpesvirus subfamilies (beta and gamma). In this review, we will compare the mechanisms of late gene transcriptional regulation between HSV-1, for which the viral IE transcription factors - especially ICP4 - play an essential role, and the two other subfamilies of herpesviruses, with a particular emphasis on EBV, which has recently been found to code for its own specific TATT-binding protein. PMID- 27375593 TI - Regulation of Intertidal Microphytobenthos Photosynthesis Over a Diel Emersion Period Is Strongly Affected by Diatom Migration Patterns. AB - Changes in biomass and photosynthesis of a diatom-dominated microphytobenthos (MPB) intertidal community were studied over a diel emersion period using a combination of O2 and scalar irradiance microprofiling, variable chlorophyll (Chl) fluorescence, and pigment analysis. The MPB biomass in the photic zone (0 0.5 mm) of the sediment exposed to low irradiance (150 MUmol photons m(-2) s(-1)) showed a >2-fold increase during the first hours of the emersion period, reaching >0.2 mg Chl a cm(-3). Concentrations of Chl a started to decrease half-way through the emersion period, almost 2 h before tidal inundation. Similarly, O2 concentrations and volumetric gross photosynthesis in the photic zone increased during the first half of the emersion period and then decreased toward the timing of incoming tide/darkness. The results suggest that intertidal MPB community level photosynthesis is mainly controlled by changes in the productive biomass of the photic zone determined by cell migration. A diel pattern in the photosynthesis vs. irradiance parameters alpha (photosynthetic efficiency at limiting irradiance) and ETR max (photosynthetic capacity at saturating irradiance) was also observed, suggesting photoacclimation of MPB. Under high light exposure (2000 MUmol photons m(-2) s(-1)), lower alpha, ETR max and sediment O2 concentrations were observed when cell migration was inhibited with the diatom motility inhibitor latrunculin A (Lat A), showing that migration is also used by MPB to maximize photosynthesis by reducing exposure to potentially photoinhibitory light levels. A higher de-epoxidation state in sediment treated with Lat A indicates that the involvement of the xanthophyll cycle in physiological photoprotection is more relevant in MPB when cells are inhibited from migrating. In the studied diatom-dominated MPB intertidal community, cell migration seems to be the key factor regulating photosynthesis over a diel emersion period and upon changes in light exposure. PMID- 27375592 TI - Pseudomonas aeruginosa Outer Membrane Vesicles Triggered by Human Mucosal Fluid and Lysozyme Can Prime Host Tissue Surfaces for Bacterial Adhesion. AB - Pseudomonas aeruginosa is a leading cause of human morbidity and mortality that often targets epithelial surfaces. Host immunocompromise, or the presence of indwelling medical devices, including contact lenses, can predispose to infection. While medical devices are known to accumulate bacterial biofilms, it is not well understood why resistant epithelial surfaces become susceptible to P. aeruginosa. Many bacteria, including P. aeruginosa, release outer membrane vesicles (OMVs) in response to stress that can fuse with host cells to alter their function. Here, we tested the hypothesis that mucosal fluid can trigger OMV release to compromise an epithelial barrier. This was tested using tear fluid and corneal epithelial cells in vitro and in vivo. After 1 h both human tear fluid, and the tear component lysozyme, greatly enhanced OMV release from P. aeruginosa strain PAO1 compared to phosphate buffered saline (PBS) controls (~100-fold). Transmission electron microscopy (TEM) and SDS-PAGE showed tear fluid and lysozyme-induced OMVs were similar in size and protein composition, but differed from biofilm-harvested OMVs, the latter smaller with fewer proteins. Lysozyme induced OMVs were cytotoxic to human corneal epithelial cells in vitro and murine corneal epithelium in vivo. OMV exposure in vivo enhanced Ly6G/C expression at the corneal surface, suggesting myeloid cell recruitment, and primed the cornea for bacterial adhesion (~4-fold, P < 0.01). Sonication disrupted OMVs retained cytotoxic activity, but did not promote adhesion, suggesting the latter required OMV-mediated events beyond cell killing. These data suggest that mucosal fluid induced P. aeruginosa OMVs could contribute to loss of epithelial barrier function during medical device-related infections. PMID- 27375594 TI - Relationship between Cefquinome PK/PD Parameters and Emergence of Resistance of Staphylococcus aureus in Rabbit Tissue-Cage Infection Model. AB - In order to explore the relationship between different antibiotic dosing regimens and selective enrichment of resistant strains, tissue-cage infection model was established in rabbits to study relationship between cefquinome pharmacokinetic/pharmacodynamic parameters and the change of susceptibility of Staphylococcus aureus (S. aureus). In this model, above 10(8) CFU/mL of S. aureus culture were exposed to cefquinome concentrations below the MIC99 (the minimal concentration that inhibits colony formation by 99% in vitro, 0.3 MUg/mL), between the MIC99 and the MPC (the mutant prevent concentration in vitro, 1.6 MUg/mL), and above the MPC after intramuscular injection with cefquinome at doses of 4, 8, 16, and 32 mg/kg of body weight (bw) once daily for 5 days or 4, 8, 16, and 24 mg/kg of bw twice daily for 2.5 days. Samples of tissue-cage fluid were collected from the tissue-cage at 2, 4, 6, 8, 10, 12, 24 h after each dosing (one dosing daily) or at 2, 4, 6, 8, 10, and 12 h (two dosing daily). Cefquinome concentration, susceptibility of S. aureus to cefquinome, and bacterial numbers at the infected site were monitored. The MICs of S. aureus and the fraction of resistant bacteria both increased when cefquinome concentrations fluctuated between the MIC99 and MPC. Resistant bacteria were selected in vivo when %T > MPC was < 58% of administration interval or %T > MIC99 was >=70% of administration interval. These findings demonstrate that low-level, cefquinome-resistant S. aureus were selected predominantly when drug concentrations fell inside a concentration window in in vivo model, which was evidenced by pulsed-field gel electrophoresis. The selection of resistant bacteria arose from both susceptible bacteria being killed and resistant bacteria re-growth. Keeping drug concentrations above the MPC for >=58% of administration interval provides a strategy to achieve effective antibacterial activity and minimize the emergence of resistance to cefquinome. PMID- 27375595 TI - DGV: Dengue Genographic Viewer. AB - Dengue viruses (DENVs) and their vectors are widely distributed throughout the tropical and subtropical regions of the world. An autochthonous case of DENV was reported in Tokyo, Japan, in 2014, for the first time in 70 years. A comprehensive database of DENV sequences containing both serotype and genotype data and epidemiological data is crucial to trace DENV outbreak isolates and promptly respond to outbreaks. We constructed a DENV database containing the serotype, genotype, year and country/region of collection by collecting all publically available DENV sequence information from the National Center for Biotechnology Information (NCBI) and assigning genotype information. We also implemented the web service Dengue Genographic Viewer (DGV), which shows the geographical distribution of each DENV genotype in a user-specified time span. DGV also assigns the serotype and genotype to a user-specified sequence by performing a homology search against the curated DENV database, and shows its homologous sequences with the geographical position and year of collection. DGV also shows the distribution of DENV-infected entrants to Japan by plotting epidemiological data from the Infectious Agents Surveillance Report (IASR), Japan. This overview of the DENV genotype distribution may aid in planning for the control of DENV infections. DGV is freely available online at: (https://gph.niid.go.jp/geograph/dengue/content/genomemap). PMID- 27375597 TI - Phylogenomic Study of Burkholderia glathei-like Organisms, Proposal of 13 Novel Burkholderia Species and Emended Descriptions of Burkholderia sordidicola, Burkholderia zhejiangensis, and Burkholderia grimmiae. AB - Partial gyrB gene sequence analysis of 17 isolates from human and environmental sources revealed 13 clusters of strains and identified them as Burkholderia glathei clade (BGC) bacteria. The taxonomic status of these clusters was examined by whole-genome sequence analysis, determination of the G+C content, whole-cell fatty acid analysis and biochemical characterization. The whole-genome sequence based phylogeny was assessed using the Genome Blast Distance Phylogeny (GBDP) method and an extended multilocus sequence analysis (MLSA) approach. The results demonstrated that these 17 BGC isolates represented 13 novel Burkholderia species that could be distinguished by both genotypic and phenotypic characteristics. BGC strains exhibited a broad metabolic versatility and developed beneficial, symbiotic, and pathogenic interactions with different hosts. Our data also confirmed that there is no phylogenetic subdivision in the genus Burkholderia that distinguishes beneficial from pathogenic strains. We therefore propose to formally classify the 13 novel BGC Burkholderia species as Burkholderia arvi sp. nov. (type strain LMG 29317(T) = CCUG 68412(T)), Burkholderia hypogeia sp. nov. (type strain LMG 29322(T) = CCUG 68407(T)), Burkholderia ptereochthonis sp. nov. (type strain LMG 29326(T) = CCUG 68403(T)), Burkholderia glebae sp. nov. (type strain LMG 29325(T) = CCUG 68404(T)), Burkholderia pedi sp. nov. (type strain LMG 29323(T) = CCUG 68406(T)), Burkholderia arationis sp. nov. (type strain LMG 29324(T) = CCUG 68405(T)), Burkholderia fortuita sp. nov. (type strain LMG 29320(T) = CCUG 68409(T)), Burkholderia temeraria sp. nov. (type strain LMG 29319(T) = CCUG 68410(T)), Burkholderia calidae sp. nov. (type strain LMG 29321(T) = CCUG 68408(T)), Burkholderia concitans sp. nov. (type strain LMG 29315(T) = CCUG 68414(T)), Burkholderia turbans sp. nov. (type strain LMG 29316(T) = CCUG 68413(T)), Burkholderia catudaia sp. nov. (type strain LMG 29318(T) = CCUG 68411(T)) and Burkholderia peredens sp. nov. (type strain LMG 29314(T) = CCUG 68415(T)). Furthermore, we present emended descriptions of the species Burkholderia sordidicola, Burkholderia zhejiangensis and Burkholderia grimmiae. The GenBank/EMBL/DDBJ accession numbers for the 16S rRNA and gyrB gene sequences determined in this study are LT158612-LT158624 and LT158625-LT158641, respectively. PMID- 27375596 TI - Bioactive Molecules Released in Food by Lactic Acid Bacteria: Encrypted Peptides and Biogenic Amines. AB - Lactic acid bacteria (LAB) can produce a huge amount of bioactive compounds. Since their elective habitat is food, especially dairy but also vegetal food, it is frequent to find bioactive molecules in fermented products. Sometimes these compounds can have adverse effects on human health such as biogenic amines (tyramine and histamine), causing allergies, hypertensive crises, and headache. However, some LAB products also display benefits for the consumers. In the present review article, the main nitrogen compounds produced by LAB are considered. Besides biogenic amines derived from the amino acids tyrosine, histidine, phenylalanine, lysine, ornithine, and glutamate by decarboxylation, interesting peptides can be decrypted by the proteolytic activity of LAB. LAB proteolytic system is very efficient in releasing encrypted molecules from several proteins present in different food matrices. Alpha and beta-caseins, albumin and globulin from milk and dairy products, rubisco from spinach, beta conglycinin from soy and gluten from cereals constitute a good source of important bioactive compounds. These encrypted peptides are able to control nutrition (mineral absorption and oxidative stress protection), metabolism (blood glucose and cholesterol lowering) cardiovascular function (antithrombotic and hypotensive action), infection (microbial inhibition and immunomodulation) and gut-brain axis (opioids and anti-opioids controlling mood and food intake). Very recent results underline the role of food-encrypted peptides in protein folding (chaperone-like molecules) as well as in cell cycle and apoptosis control, suggesting new and positive aspects of fermented food, still unexplored. In this context, the detailed (transcriptomic, proteomic, and metabolomic) characterization of LAB of food interest (as starters, biocontrol agents, nutraceuticals, and probiotics) can supply a solid evidence-based science to support beneficial effects and it is a promising approach as well to obtain functional food. The detailed knowledge of the modulation of human physiology, exploiting the health-promoting properties of fermented food, is an open field of investigation that will constitute the next challenge. PMID- 27375599 TI - Autophagy and Reactive Oxygen Species Are Involved in Neutrophil Extracellular Traps Release Induced by C. albicans Morphotypes. AB - Neutrophil extracellular traps (NETs) are a combination of DNA fibers and granular enzymes, such as elastase and myeloperoxidase. In this study, we demonstrate that Candida albicans hyphal (CAH) cells and yeast (CAY) cells induce differential amounts, kinetics and mechanisms of NET release. CAH cells induced larger quantities of NET compared to CAY cells and can stimulate rapid NET formation up to 4 h of incubation. CAY cells are, also, able to induce rapid NET formation, but this ability was lost at 4 h. Both reactive oxygen species (ROS) and autophagy are implicated in NET induced by CAH and CAY cells, but with a time different participation of these two mechanisms. In particular, in the early phase (15 min) CAH cells stimulate NET via autophagy, but not via ROS, while CAY cells induce NET via both autophagy and ROS. At 4 h, only CAH cells stimulate NET formation using autophagy as well as ROS. Finally, we demonstrate that NET release, in response to CAH cells, involves NF-kappaB activation and is strongly implicated in hyphal destruction. PMID- 27375598 TI - Extracellular Proteins: Novel Key Components of Metal Resistance in Cyanobacteria? AB - Metals are essential for all living organisms and required for fundamental biochemical processes. However, when in excess, metals can turn into highly-toxic agents able to disrupt cell membranes, alter enzymatic activities, and damage DNA. Metal concentrations are therefore tightly controlled inside cells, particularly in cyanobacteria. Cyanobacteria are ecologically relevant prokaryotes that perform oxygenic photosynthesis and can be found in many different marine and freshwater ecosystems, including environments contaminated with heavy metals. As their photosynthetic machinery imposes high demands for metals, homeostasis of these micronutrients has been widely studied in cyanobacteria. So far, most studies have focused on how cells are capable of controlling their internal metal pools, with a strong bias toward the analysis of intracellular processes. Ultrastructure, modulation of physiology, dynamic changes in transcription and protein levels have been studied, but what takes place in the extracellular environment when cells are exposed to an unbalanced metal availability remains largely unknown. The interest in studying the subset of proteins present in the extracellular space has only recently begun and the identification and functional analysis of the cyanobacterial exoproteomes are just emerging. Remarkably, metal-related proteins such as the copper-chaperone CopM or the iron-binding protein FutA2 have already been identified outside the cell. With this perspective, we aim to raise the awareness that metal-resistance mechanisms are not yet fully known and hope to motivate future studies assessing the role of extracellular proteins on bacterial metal homeostasis, with a special focus on cyanobacteria. PMID- 27375600 TI - Genetic Manipulation of Competition for Nitrate between Heterotrophic Bacteria and Diatoms. AB - Diatoms are a dominant group of eukaryotic phytoplankton that contribute substantially to global primary production and the cycling of important elements such as carbon and nitrogen. Heterotrophic bacteria, including members of the gammaproteobacteria, are commonly associated with diatom populations and may rely on them for organic carbon while potentially competing with them for other essential nutrients. Considering that bacterioplankton drive oceanic release of CO 2 (i.e., bacterial respiration) while diatoms drive ocean carbon sequestration vial the biological pump, the outcome of such competition could influence the direction and magnitude of carbon flux in the upper ocean. Nitrate availability is commonly a determining factor for the growth of diatom populations, particularly in coastal and upwelling regions. Diatoms as well as many bacterial species can utilize nitrate, however the ability of bacteria to compete for nitrate may be hindered by carbon limitation. Here we have developed a genetically tractable model system using the pennate diatom Phaeodactylum tricornutum and the widespread heterotrophic bacteria Alteromonas macleodii to examine carbon-nitrogen dynamics. While subsisting solely on P. tricornutum derived carbon, A. macleodii does not appear to be an effective competitor for nitrate, and may in fact benefit the diatom; particularly in stationary phase. However, allochthonous dissolved organic carbon addition in the form of pyruvate triggers A. macleodii proliferation and nitrate uptake, leading to reduced P. tricornutum growth. Nitrate reductase deficient mutants of A. macleodii (DeltanasA) do not exhibit such explosive growth and associated competitive ability in response to allochthonous carbon when nitrate is the sole nitrogen source, but could survive by utilizing solely P. tricornutum-derived nitrogen. Furthermore, allocthonous carbon addition enables wild-type A. macleodii to rescue nitrate reductase deficient P. tricornutum populations from nitrogen starvation, and RNA-seq transcriptomic evidence supports nitrogen-based interactions between diatoms and bacteria at the molecular level. This study provides key insights into the roles of carbon and nitrogen in phytoplankton bacteria dynamics and lays the foundation for developing a mechanistic understanding of these interactions using co-culturing and genetic manipulation. PMID- 27375601 TI - Corrigendum: Modulation of Type III Secretion System in Pseudomonas aeruginosa: Involvement of the PA4857 Gene Product. AB - [This corrects the article on p. 7 in vol. 7, PMID: 26858696.]. PMID- 27375602 TI - The Developing World Urgently Needs Phages to Combat Pathogenic Bacteria. PMID- 27375603 TI - Sld3-MCM Interaction Facilitated by Dbf4-Dependent Kinase Defines an Essential Step in Eukaryotic DNA Replication Initiation. AB - Sld3/Treslin is an evolutionarily conserved protein essential for activation of DNA helicase Mcm2-7 and replication initiation in all eukaryotes. Nevertheless, it remains elusive how Sld3 is recruited to origins. Here, we have identified the direct physical association of Sld3 with Mcm2 and Mcm6 subunits in vitro, which is significantly enhanced by DDK in vivo. The Sld3-binding domain (SBD) is mapped to the N-termini of Mcm2 and Mcm6, both of them are essential for cell viability and enriched with the DDK phosphorylation sites. Glutamic acid substitution of four conserved positively charged residues of Sld3 (sld3-4E), near the Cdc45 binding region, interrupts its interaction with Mcm2/6 and causes cell death. By using a temperature-inducible degron (td), we show that deletion of Mcm6 SBD (mcm6DeltaN122) abolishes not only Sld3 enrichment at early origins in G1 phase, but also subsequent recruitment of GINS and RPA during S phase. These findings elucidate the in vivo molecular details of the DDK-dependent Sld3-MCM association, which plays a crucial role in MCM helicase activation and origin unwinding. PMID- 27375604 TI - Fitness Trade-Offs in Competence Differentiation of Bacillus subtilis. AB - In the stationary phase, Bacillus subtilis differentiates stochastically and transiently into the state of competence for transformation (K-state). The latter is associated with growth arrest, and it is unclear how the ability to develop competence is stably maintained, despite its cost. To quantify the effect differentiation has on the competitive fitness of B. subtilis, we characterized the competition dynamics between strains with different probabilities of entering the K-state. The relative fitness decreased with increasing differentiation probability both during the stationary phase and during outgrowth. When exposed to antibiotics inhibiting cell wall synthesis, transcription, and translation, cells that differentiated into the K-state showed a selective advantage compared to differentiation-deficient bacteria; this benefit did not require transformation. Although beneficial, the K-state was not induced by sub-MIC concentrations of antibiotics. Increasing the differentiation probability beyond the wt level did not significantly affect the competition dynamics with transient antibiotic exposure. We conclude that the competition dynamics are very sensitive to the fraction of competent cells under benign conditions but less sensitive during antibiotic exposure, supporting the picture of stochastic differentiation as a fitness trade-off. PMID- 27375605 TI - Epimicrobiota Associated with the Decay and Recovery of Orbicella Corals Exhibiting Dark Spot Syndrome. AB - Dark Spot Syndrome (DSS) is one of the most common diseases of boulder corals in the Caribbean. It presents as sunken brown lesions in coral tissue, which can spread quickly over coral colonies. With this study, we tested the hypothesis that similar to other coral diseases, DSS is a dysbiosis characterized by global shifts in the coral microbiome. Because Black Band Disease (BBD) was sometimes found following DSS lesions, we also tested the hypothesis that DSS is a precursor of BBD. To track disease initiation and progression 24 coral colonies were tagged. Of them five Orbicella annularis corals and three O. faveolata corals exhibited DSS lesions at tagging. Microbiota of lesions and apparently healthy tissues from DSS-affected corals over the course of 18 months were collected. Final visual assessment showed that five of eight corals incurred substantial tissue loss while two corals remained stable and one appeared to recover from DSS lesions. Illumina sequencing of the V6 region of bacterial 16S rRNA genes demonstrated no significant differences in bacterial community composition associated with healthy tissue or DSS lesions. The epimicrobiomes of both healthy tissue and DSS lesions contained high relative abundances of Operational Taxonomic Units assigned to Halomonas, an unclassified gammaproteobacterial genus, Moritella, an unclassified Rhodobacteraceae genus, Renibacterium, Pseudomonas, and Acinetobacter. The relative abundance of bacterial taxa was not significantly different between samples when grouped by tissue type (healthy tissue vs. DSS lesion), coral species, collection month, or the overall outcome of DSS-affected corals (substantial tissue loss vs. stable/recovered). Two of the tagged corals with substantial tissue loss also developed BBD during the 18-month sampling period. The bacterial community of the BBD layer was distinct from both healthy tissue and DSS lesions, with high relative abundances of the presumed BBD pathogen Roseofilum reptotaenium and an unclassified Bacteroidales genus, similar to previous results. Roseofilum was detected in all samples from this study, with the highest relative abundance in healthy tissue from DSS-affected corals sampled in August, suggesting that while DSS is not a precursor to BBD, DSS-affected corals are in a weakened state and therefore more susceptible to additional infections. PMID- 27375606 TI - Differences in Enzymatic Properties of the Saccharomyces kudriavzevii and Saccharomyces uvarum Alcohol Acetyltransferases and Their Impact on Aroma-Active Compounds Production. AB - Higher alcohols and acetate esters belong to the most important yeast secondary metabolites that significantly contribute to the overall flavor and aroma profile of fermented products. In Saccharomyces cerevisiae, esterification of higher alcohols is catalyzed mainly by the alcohol acetyltransferases encoded by genes ATF1 and ATF2. Previous investigation has shown other Saccharomyces species, e.g., S. kudriavzevii and S. uvarum, to vary in aroma-active higher alcohols and acetate esters formation when compared to S. cerevisiae. Here, we aimed to analyze the enzymes encoded by the ATF1 and ATF2 genes from S. kudriavzevii (SkATF1, SkATF2) and S. uvarum (SuATF1, SuATF2). The heterologous expression of the individual ATF1 and ATF2 genes in a host S. cerevisiae resulted in the enhanced production of several higher alcohols and acetate esters. Particularly, an increase of 2-phenylethyl acetate production by the strains that harbored ATF1 and ATF2 genes from S. kudriavzevii and S. uvarum was observed. When grown with individual amino acids as the nitrogen source, the strain that harbored SkATF1 showed particularly high 2-phenylethyl acetate production and the strains with introduced SkATF2 or SuATF2 revealed increased production of isobutyl acetate, isoamyl acetate, and 2-phenylethyl acetate compared to the reference strains with endogenous ATF genes. The alcohol acetyltransferase activities of the individual Atf1 and Atf2 enzymes measured in the cell extracts of the S. cerevisiae atf1 atf2 iah1 triple-null strain were detected for all the measured substrates. This indicated that S. kudriavzevii and S. uvarum Atf enzymes had broad range substrate specificity as S. cerevisiae Atf enzymes. Individual Atf1 enzymes exhibited markedly different kinetic properties since SkAtf1p showed c. twofold higher and SuAtf1p c. threefold higher K m for isoamyl alcohol than ScAtf1p. Together these results indicated that the differences found among the three Saccharomyces species during the aroma-active acetate ester formation may be due, to some extent, to the distinct properties of Atf enzymes. PMID- 27375607 TI - The Role of Neutrophils in the Induction of Specific Th1 and Th17 during Vaccination against Tuberculosis. AB - Mycobacterium tuberculosis causes tuberculosis (TB), a disease that killed more than 1.5 million people worldwide in 2014, and the Bacillus Calmette Guerin (BCG) vaccine is the only currently available vaccine against TB. However, it does not protect adults. Th1 and Th17 cells are crucial for TB control, as well as the neutrophils that are directly involved in DC trafficking to the draining lymph nodes and the activation of T lymphocytes during infection. Although several studies have shown the importance of neutrophils during M. tuberculosis infection, none have shown its role in the development of a specific response to a vaccine. The vaccine mc(2)-CMX was shown to protect mice against M. tuberculosis challenge, mainly due to specific Th1 and Th17 cells. This study evaluated the importance of neutrophils in the generation of the Th1- and Th17 specific responses elicited by this vaccine. The vaccine injection induced a neutrophil rich lesion with a necrotic central area. The IL-17 KO mice did not generate vaccine-specific Th1 cells. The vaccinated IL-22 KO mice exhibited Th1- and Th17-specific responses. Neutrophil depletion during vaccination abrogated the induction of Th1-specific responses and prohibited the bacterial load reduction observed in the vaccinated animals. The results show, for the first time, the role of neutrophils in the generation of specific Th1 and Th17 cells in response to a tuberculosis vaccine. PMID- 27375608 TI - The MqsRA Toxin-Antitoxin System from Xylella fastidiosa Plays a Key Role in Bacterial Fitness, Pathogenicity, and Persister Cell Formation. AB - Through the formation of persister cells, bacteria exhibit tolerance to multidrug and other environmental stresses without undergoing genetic changes. The toxin antitoxin (TA) systems are involved in the formation of persister cells because they are able to induce cell dormancy. Among the TA systems, the MqsRA system has been observed to be highly induced in persister cells of Xylella fastidiosa (causal agent of citrus variegated chlorosis-CVC) activated by copper stress, and has been described in Escherichia coli as related to the formation of persister cells and biofilms. Thus, we evaluated the role of this TA system in X. fastidiosa by overexpressing the MqsR toxin, and verified that the toxin positively regulated biofilm formation and negatively cell movement, resulting in reduced pathogenicity in citrus plants. The overexpression of MqsR also increased the formation of persister cells under copper stress. Analysis of the gene and protein expression showed that this system likely has an autoregulation mechanism to express the toxin and antitoxin in the most beneficial ratio for the cell to oppose stress. Our results suggest that this TA system plays a key role in the adaptation and survival of X. fastidiosa and reveal new insights into the physiology of phytopathogen-host interactions. PMID- 27375609 TI - An Integrated Multi-Omics Approach Reveals the Effects of Supplementing Grass or Grass Hay with Vitamin E on the Rumen Microbiome and Its Function. AB - Rumen function is generally suboptimal leading to losses in methane and nitrogen. Analysis of the rumen microbiome is thus important to understanding the underlying microbial activity under different feeding strategies. This study investigated the effect of forage conservation method and vitamin E supplementation on rumen function using a rumen simulation technique. Ryegrass (GRA) or ryegrass hay (HAY) was supplemented with 20% concentrate containing zero or 50 IU/d vitamin E, as alpha-tocopheryl acetate, according to a 2 * 2 factorial design. The forage conservation method did not substantially change the nutrient composition but had a profound impact on the structure and diversity of the rumen microbiome. HAY diets promoted a more complex bacterial community (+38 OTUs) dominated by Firmicutes. This bacterial adaptation, together with increased rumen protozoa levels and methanogen diversity, was associated with greater fiber disappearance (+12%) in HAY diets, but also with greater rumen true N degradability (+7%) than GRA diets. HAY diets also had a higher metabolic H recovery and methane production (+35%) suggesting more efficient inter-species H transfer between bacteria, protozoa and methanogens. Contrarily, GRA diets promoted more simplified methanogen and bacterial communities, which were dominated by Bacteroidetes and Lactobacillus, thus lactate formation may have acted as an alternative H sink in GRA diets. Moreover the structure of the bacterial community with GRA diets was highly correlated with N utilization, and GRA diets promoted greater bacterial growth and microbial protein synthesis (+16%), as well as a more efficient microbial protein synthesis (+22%). A dose response experiment using batch cultures revealed that vitamin E supplementation increased rumen fermentation in terms of total VFA and gas production, with protozoal activity higher when supplying alpha-tocopheryl acetate vs. alpha tocopherol. Moreover, alpha-tocopheryl acetate promoted a small increase in feed degradability (+8%), possibly as a result of its antioxidant properties which led to higher bacterial and protozoal levels. Vitamin E supplementation also modified the levels of some methanogen species indicating that they may be particularly sensitive to oxidative stresses. Our findings suggested that when possible, grass should be fed instead of grass hay, in order to improve rumen function and to decrease the environmental impact of livestock agriculture. PMID- 27375610 TI - A Friendly Relationship between Endophytic Fungi and Medicinal Plants: A Systematic Review. AB - Endophytic fungi or endophytes exist widely inside the healthy tissues of living plants, and are important components of plant micro-ecosystems. Over the long period of evolution, some co-existing endophytes and their host plants have established a special relationship with one and another, which can significantly influence the formation of metabolic products in plants, then affect quality and quantity of crude drugs derived from medicinal plants. This paper will focus on the increasing knowledge of relationships between endophytic fungi and medicinal plants through reviewing of published research data obtained from the last 30 years. The analytical results indicate that the distribution and population structure of endophytes can be considerably affected by factors, such as the genetic background, age, and environmental conditions of their hosts. On the other hand, the endophytic fungi can also confer profound impacts on their host plants by enhancing their growth, increasing their fitness, strengthening their tolerances to abiotic and biotic stresses, and promoting their accumulation of secondary metabolites. All the changes are very important for the production of bioactive components in their hosts. Hence, it is essential to understand such relationships between endophytic fungi and their host medicinal plants. Such knowledge can be well exploited and applied for the production of better and more drugs from medicinal plants. PMID- 27375611 TI - Genetic Characterization of Staphylococcus aureus Isolated from Retail Meat in Riyadh, Saudi Arabia. AB - Limited data exist from the Gulf Cooperation Council states on the prevalence and population dynamics of Staphylococcus aureus colonizing livestock or contaminating retail meat. This study was designed to determine the presence and genetic characteristics of Staphylococcus aureus isolated from raw retail meat sold in Riyadh, Saudi Arabia. Over a period of 9 months, different raw retail meat types were aseptically processed using the double broth enrichment technique, characteristic colonies from chromogenic and mannitol salt agar were further identified using conventional methods. Susceptibility to 9 antibiotics was determined using the disc diffusion technique. Interpretation of inhibition zone was done according to Clinical and Laboratory Standards Institute guidelines. Molecular characterization was carried out using the StaphyType DNA microarray technology. Twenty-five meat samples yielded Staphylococcus aureus isolates. Camel meat had the highest contamination rate with Methicillin resistant Staphylococcus aureus (MRSA) (20%) and Methicillin susceptible Staphylococcus aureus (28%), while poultry meat had the least contamination rate with MRSA (4%). The MRSA isolates were grouped into 4 clonal complexes (CCs) namely CC1-MRSA-IV/SCCfus (n = 2), CC15-MRSA-V/SCCfus (n = 4), CC80-MRSA-IV/PVL+ (n = 5), and CC88-MRSA-IV/PVL+ (n = 2). All CC15-MRSA-V/SCCfus isolates were obtained from camel meat. This is the first study to demonstrate the novel CC15 MRSA-V/SCCfus in retail camel meat. We recommend that surveillance studies should be incorporated in public health and food hygiene programs. PMID- 27375612 TI - Viable Compositional Analysis of an Eleven Species Oral Polymicrobial Biofilm. AB - PURPOSE: Polymicrobial biofilms are abundant in clinical disease, particularly within the oral cavity. Creating complex biofilm models that recapitulate the polymicrobiality of oral disease are important in the development of new chemotherapeutic agents. In order to do this accurately we require the ability to undertake compositional analysis, in addition to determine individual cell viability, which is difficult using conventional microbiology. The aim of this study was to develop a defined multispecies denture biofilm model in vitro, and to assess viable compositional analysis following defined oral hygiene regimens. METHODS: An in vitro multispecies denture biofilm containing various oral commensal and pathogenic bacteria and yeast was created on poly (methyl methacrylate) (PMMA). Denture hygiene regimens tested against the biofilm model included brushing only, denture cleansing only and combinational brushing and denture cleansing. Biofilm composition and viability were assessed by culture (CFU) and molecular (qPCR) methodologies. Scanning electron microscopy and confocal laser scanning microscopy were also employed to visualize changes in denture biofilms following treatment. RESULTS: Combinational treatment of brushing and denture cleansing had the greatest impact on multispecies denture biofilms, reducing the number of live cells by more than 2 logs, and altering the overall composition in favor of streptococci. This was even more evident during the sequential testing, whereby daily sequential treatment reduced the total and live number of bacteria and yeast more than those treated intermittently. Bacteria and yeast remaining following treatment tended to aggregate in the pores of the PMMA, proving more difficult to fully eradicate the biofilm. CONCLUSIONS: Overall, we are the first to develop a method to enable viable compositional analysis of an 11 species denture biofilm following chemotherapeutic challenge. We were able to demonstrate viable cell reduction and changes in population dynamics following evaluation of various denture cleansing regimens. Specifically, it was demonstrated that daily combinational treatment of brushing and cleansing proved to be the most advantageous denture hygiene regimen, however, residual organisms still remained within the pores of PMMA surface, which could act as a reservoir for further biofilm regrowth. We have identified an industry need for denture cleansing agents with the capacity to penetrate these pores and disaggregate these complex biofilm consortia. PMID- 27375613 TI - HIV-Exposed Uninfected Infants in Zimbabwe: Insights into Health Outcomes in the Pre-Antiretroviral Therapy Era. AB - The ZVITAMBO trial recruited 14,110 mother-infant pairs to a randomized controlled trial of vitamin A between 1997 and 2000, before the availability of antiretroviral therapy for HIV prophylaxis or treatment in Zimbabwe. The HIV status of mothers and infants was well characterized through 1-2 years of follow up, leading to the largest cohort to date of HIV-exposed uninfected (HEU) infants (n = 3135), with a suitable comparison group of HIV-unexposed infants (n = 9510). Here, we draw on 10 years of published findings from the ZVITAMBO trial. HEU infants had increased morbidity compared to HIV-unexposed infants, with 50% more hospitalizations in the neonatal period and 30% more sick clinic visits during infancy, particularly for skin infections, lower respiratory tract infections, and oral thrush. HEU children had 3.9-fold and 2.0-fold higher mortality than HIV unexposed children during the first and second years of life, respectively, most commonly due to acute respiratory infections, diarrhea/dysentery, malnutrition, sepsis, and meningitis. Infant morbidity and mortality were strongly related to maternal HIV disease severity, and increased morbidity remained until maternal CD4 counts were >800 cells/MUL. HEU infants were more likely to be premature and small-for-gestational age than HIV-unexposed infants, and had more postnatal growth failure. Here, we propose a conceptual framework to explain the increased risk of infectious morbidity, mortality, and growth failure among HEU infants, hypothesizing that immune activation and inflammation are key drivers of both infection susceptibility and growth failure. Future studies should further dissect the causes of infection susceptibility and growth failure and determine the impact of ART and cotrimoxazole on outcomes of this vulnerable group of infants in the current era. PMID- 27375615 TI - Evasins: Therapeutic Potential of a New Family of Chemokine-Binding Proteins from Ticks. AB - Blood-sucking parasites, such as ticks, remain attached to their hosts for relatively long periods of time in order to obtain their blood meal without eliciting an immune response. One mechanism used to avoid rejection is the inhibition of the recruitment of immune cells, which can be achieved by a class of chemokine-binding proteins (CKBPs) known as Evasins. We have identified three distinct Evasins produced by the salivary glands of the common brown dog tick, Rhipicephalus sanguineus. They display different selectivities for chemokines, the first two identified show a narrow selectivity profile, while the third has a broader binding spectrum. The Evasins showed efficacy in animal models of inflammatory disease. Here, we will discuss the potential of their development for therapeutic use, addressing both the advantages and disadvantages that this entails. PMID- 27375616 TI - Immunoglobulin Transporting Receptors Are Potential Targets for the Immunity Enhancement and Generation of Mammary Gland Bioreactor. AB - The functions of immunoglobulin transporting receptors (Ig transporting receptors) in immune system encompass from passive immunity to adaptive immunity by transporting immunoglobulins (Igs) and prolonging their half-life as well as enhancing immunosurveillance. Prior to the weaning, Ig transportations from mother to offspring confer the immediate passive immunity for neonates. After the weaning, FcRn and polymeric immunoglobulin receptor on infant intestinal epithelial cells retrieve Ig in intestinal lamina propria into the gut lumen for preventing pathogen invasion. This is not only improving the pathological consequences of infection but also helping the neonates for developing their own immune response; besides it would be the guidance for designing novel vaccines. Moreover, the investigations on Ig transporting receptors over-expressed transgenic animals have been carried out to improve Ig concentrations in serum and milk; thus, it would be a sustainable method to produce antibody-enriched milk-derived colostrum replacer for neonates. In order to generate mammary gland bioreactor, a series of methods have been developed for enhanced regulation of Ig transporting receptors expression and Ig transportation. PMID- 27375614 TI - Role of Natural Autoantibodies and Natural IgM Anti-Leucocyte Autoantibodies in Health and Disease. AB - We review how polyreactive natural IgM autoantibodies (IgM-NAA) protect the host from invading micro-organisms and host neo-antigens that are constantly being produced by oxidation mechanisms and cell apoptosis. Second, we discuss how IgM NAA and IgM anti-leukocyte antibodies (IgM-ALA) inhibits autoimmune inflammation by anti-idiotypic mechanisms, enhancing removal of apoptotic cells, masking neo antigens, and regulating the function of dendritic cells (DC) and effector cells. Third, we review how natural IgM prevents autoimmune disorders arising from pathogenic IgG autoantibodies, triggered by genetic mechanisms (e.g., SLE) or micro-organisms, as well as by autoreactive B and T cells that have escaped tolerance mechanisms. Studies in IgM knockout mice have clearly demonstrated that regulatory B and T cells require IgM to effectively regulate inflammation mediated by innate, adaptive, and autoimmune mechanisms. It is, therefore, not surprising why the host positively selects such autoreactive B1 cells that generate IgM-NAA, which are also evolutionarily conserved. Fourth, we show that IgM-ALA levels and their repertoire can vary in normal humans and disease states and this variation may partly explain the observed differences in the inflammatory response after infection, ischemic injury, or after a transplant. We also show how protective IgM-NAA can be rendered pathogenic under non physiological conditions. We also review IgG-NAA that are more abundant than IgM NAA in plasma. However, we need to understand if the (Fab)(2) region of IgG-NAA has physiological relevance in non-disease states, as in plasma, their functional activity is blocked by IgM-NAA having anti-idiotypic activity. Some IgG-NAA are produced by B2 cells that have escaped tolerance mechanisms and we show how such pathogenic IgG-NAA are regulated to prevent autoimmune disease. The Fc region of IgG-NAA can influence inflammation and B cell function in vivo by binding to activating and inhibitory FcgammaR. IgM-NAA has therapeutic potential. Polyclonal IgM infusions can be used to abrogate on-going inflammation. Additionally, inflammation arising after ischemic kidney injury, e.g., during high-risk elective cardiac surgery or after allograft transplantation, can be prevented by pre-emptively infusing polyclonal IgM or DC pretreated ex vivo with IgM or by increasing in vivo IgM with a vaccine approach. Cell therapy is appealing as less IgM will be required. PMID- 27375617 TI - Detecting the Hidden Properties of Immunological Data and Predicting the Mortality Risks of Infectious Syndromes. AB - BACKGROUND: To extract more information, the properties of infectious disease data, including hidden relationships, could be considered. Here, blood leukocyte data were explored to elucidate whether hidden information, if uncovered, could forecast mortality. METHODS: Three sets of individuals (n = 132) were investigated, from whom blood leukocyte profiles and microbial tests were conducted (i) cross-sectional analyses performed at admission (before bacteriological tests were completed) from two groups of hospital patients, randomly selected at different time periods, who met septic criteria [confirmed infection and at least three systemic inflammatory response syndrome (SIRS) criteria] but lacked chronic conditions (study I, n = 36; and study II, n = 69); (ii) a similar group, tested over 3 days (n = 7); and (iii) non-infected, SIRS negative individuals, tested once (n = 20). The data were analyzed by (i) a method that creates complex data combinations, which, based on graphic patterns, partitions the data into subsets and (ii) an approach that does not partition the data. Admission data from SIRS+/infection+ patients were related to 30-day, in hospital mortality. RESULTS: The non-partitioning approach was not informative: in both study I and study II, the leukocyte data intervals of non-survivors and survivors overlapped. In contrast, the combinatorial method distinguished two subsets that, later, showed twofold (or larger) differences in mortality. While the two subsets did not differ in gender, age, microbial species, or antimicrobial resistance, they revealed different immune profiles. Non-infected, SIRS-negative individuals did not express the high-mortality profile. Longitudinal data from septic patients displayed the pattern associated with the highest mortality within the first 24 h post-admission. Suggesting inflammation coexisted with immunosuppression, one high-mortality sub-subset displayed high neutrophil/lymphocyte ratio values and low lymphocyte percents. A second high mortality subset showed monocyte-mediated deficiencies. Numerous within- and between-subset comparisons revealed statistically significantly different immune profiles. CONCLUSION: While the analysis of non-partitioned data can result in information loss, complex (combinatorial) data structures can uncover hidden patterns, which guide data partitioning into subsets that differ in mortality rates and immune profiles. Such information can facilitate diagnostics, monitoring of disease dynamics, and evaluation of subset-specific, patient specific therapies. PMID- 27375618 TI - The Cellular Bases of Antibody Responses during Dengue Virus Infection. AB - Dengue virus (DENV) is one of the most significant human viral pathogens transmitted by mosquitoes and can cause from an asymptomatic disease to mild undifferentiated fever, classical dengue, and severe dengue. Neutralizing memory antibody (Ab) responses are one of the most important mechanisms that counteract reinfections and are therefore the main aim of vaccination. However, it has also been proposed that in dengue, some of these class-switched (IgG) memory Abs might worsen the disease. Although these memory Abs derive from B cells by T-cell dependent processes, we know rather little about the (acute, chronic, or memory) B cell responses and the complex cellular mechanisms generating these Abs during DENV infections. This review aims to provide an updated and comprehensive perspective of the B cell responses during DENV infection, starting since the very early events such as the cutaneous DENV entrance and the arrival into draining lymph nodes, to the putative B cell activation, proliferation, and germinal centers (GCs) formation (the source of affinity-matured class-switched memory Abs), till the outcome of GC reactions such as the generation of plasmablasts, Ab-secreting plasma cells, and memory B cells. We discuss topics very poorly explored such as the possibility of B cell infection by DENV or even activation-induced B cell death. The current information about the nature of the Ab responses to DENV is also illustrated. PMID- 27375619 TI - PTSD, a Disorder with an Immunological Component. AB - Post-traumatic stress disorder (PTSD) has been associated with an inflammatory state. However, few studies have addressed the mechanisms underlying this immune imbalance that favors inflammation or how this imbalance contributes to PTSD. Whether the immune imbalance influences responsiveness or unresponsiveness of patients to PTSD treatments is currently not known. This review brings forward an immune emphasis to a mental health disorder that is unprecedented in its prevalence among combat Veterans of the ongoing conflicts in Iraq and Afghanistan and which also afflicts civilians who have undergone extreme traumatic experiences, such as following natural disasters, serious accidents, or assaults. Included is an overview of the correlative associations in human subjects between PTSD and inflammation and studies in animal models of PTSD, demonstrating causal contributions of inflammation and immune dysregulation to PTSD-like behavior following stress exposure. PMID- 27375621 TI - Editorial: The Emerging Role of Monocyte-Derived Cells in the Central Nervous System. PMID- 27375622 TI - Atypical Chemokine Receptors and Their Roles in the Resolution of the Inflammatory Response. AB - Chemokines and their receptors are key mediators of the inflammatory process regulating leukocyte extravasation and directional migration into inflamed and infected tissues. The control of chemokine availability within inflamed tissues is necessary to attain a resolving environment and when this fails chronic inflammation ensues. Accordingly, vertebrates have adopted a number of mechanisms for removing chemokines from inflamed sites to help precipitate resolution. Over the past 15 years, it has become apparent that essential players in this process are the members of the atypical chemokine receptor (ACKR) family. Broadly speaking, this family is expressed on stromal cell types and scavenges chemokines to either limit their spatial availability or to remove them from in vivo sites. Here, we provide a brief review of these ACKRs and discuss their involvement in the resolution of inflammatory responses and the therapeutic implications of our current knowledge. PMID- 27375623 TI - Peptidylarginine Deiminase Inhibitor Suppresses Neutrophil Extracellular Trap Formation and MPO-ANCA Production. AB - Myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis is a systemic small-vessel vasculitis, wherein, MPO-ANCA plays a critical role in the pathogenesis. Neutrophil extracellular traps (NETs) released from activated neutrophils are composed of extracellular web-like DNA and antimicrobial proteins, including MPO. Diverse stimuli, such as phorbol myristate acetate (PMA) and ligands of toll-like receptors (TLR), induce NETs. Although TLR mediated NET formation can occur with preservation of living neutrophilic functions (called vital NETosis), PMA-stimulated neutrophils undergo cell death with NET formation (called suicidal NETosis). In the process of suicidal NETosis, histones are citrullinated by peptidylarginine deiminase 4 (PAD4). Since this step is necessary for decondensation of DNA, PAD4 plays a pivotal role in suicidal NETosis. Although NETs are essential for elimination of microorganisms, excessive formation of NETs has been suggested to be implicated in MPO-ANCA production. This study aimed to determine if pan-PAD inhibitors could suppress MPO-ANCA production in vivo. At first, NETs were induced in peripheral blood neutrophils derived from healthy donors (1 * 10(6)/ml) by stimulation with 20 nM PMA with or without 20 MUM propylthiouracil (PTU), an anti-thyroid drug. We then determined that the in vitro NET formation was inhibited completely by 200 MUM Cl amidine, a pan-PAD inhibitor. Next, we established mouse models with MPO-ANCA production. BALB/c mice were given intraperitoneal (i.p.) injection of PMA (50 ng at days 0 and 7) and oral PTU (2.5 mg/day) for 2 weeks. These mice were divided into two groups; the first group was given daily i.p. injection of PBS (200 MUl/day) (n = 13) and the other group with daily i.p. injection of Cl-amidine (0.3 mg/200 MUl PBS/day) (n = 7). Two weeks later, citrullination as an indicator of NET formation in the peritoneum and serum MPO-ANCA titer was compared between the two groups. Results demonstrated that citrullination in the peritoneum was significantly reduced in the Cl-amidine-treated mice compared with the vehicle injected control mice (38% reduction). Additionally, the serum MPO-ANCA titer of the Cl-amidine-treated mice (32.3 +/- 31.0 ng/ml) was significantly lower than that in the vehicle-injected mice (132.1 +/- 41.6 ng/ml). The collective findings indicate that excessive formation of NETs may be implicated in MPO-ANCA production in vivo. PMID- 27375620 TI - Molecular Mechanisms for cAMP-Mediated Immunoregulation in T cells - Role of Anchored Protein Kinase A Signaling Units. AB - The cyclic AMP/protein kinase A (cAMP/PKA) pathway is one of the most common and versatile signal pathways in eukaryotic cells. A-kinase anchoring proteins (AKAPs) target PKA to specific substrates and distinct subcellular compartments providing spatial and temporal specificity for mediation of biological effects channeled through the cAMP/PKA pathway. In the immune system, cAMP is a potent negative regulator of T cell receptor-mediated activation of effector T cells (Teff) acting through a proximal PKA/Csk/Lck pathway anchored via a scaffold consisting of the AKAP Ezrin holding PKA, the linker protein EBP50, and the anchoring protein phosphoprotein associated with glycosphingolipid-enriched microdomains holding Csk. As PKA activates Csk and Csk inhibits Lck, this pathway in response to cAMP shuts down proximal T cell activation. This immunomodulating pathway in Teff mediates clinically important responses to regulatory T cell (Treg) suppression and inflammatory mediators, such as prostaglandins (PGs), adrenergic stimuli, adenosine, and a number of other ligands. A major inducer of T cell cAMP levels is PG E2 (PGE2) acting through EP2 and EP4 prostanoid receptors. PGE2 plays a crucial role in the normal physiological control of immune homeostasis as well as in inflammation and cancer immune evasion. Peripherally induced Tregs express cyclooxygenase-2, secrete PGE2, and elicit the immunosuppressive cAMP pathway in Teff as one tumor immune evasion mechanism. Moreover, a cAMP increase can also be induced by indirect mechanisms, such as intercellular transfer between T cells. Indeed, Treg, known to have elevated levels of intracellular cAMP, may mediate their suppressive function by transferring cAMP to Teff through gap junctions, which we speculate could also be regulated by PKA/AKAP complexes. In this review, we present an updated overview on the influence of cAMP-mediated immunoregulatory mechanisms acting through localized cAMP signaling and the therapeutical increasing prospects of AKAPs disruptors in T-cell immune function. PMID- 27375624 TI - Unique Transcompartmental Bridge: Antigen-Presenting Cells Sampling across Endothelial and Mucosal Barriers. AB - Potentially harmful pathogens can gain access to tissues and organ systems through body sites that are in direct contact with the outside environment, such as the skin, the gut, and the airway mucosa. Antigen-presenting cells (APCs) represent a bridge between the innate and adaptive immunity, and their capacity for constant immune surveillance and rapid sampling of incoming pathogens and other potentially harmful antigens is central for mounting an effective and robust protective host response. The classical view is that APCs perform this task efficiently within the tissue to sense invading agents intra compartmentally. However, recent data based on high resolution imaging support an additional transcompartmental surveillance behavior by APC by reaching across intact physical barriers. In this review, we summarize intravital microscopic evidences of APC to sample antigens transcompartmentally at the gut mucosa and other body sites. PMID- 27375625 TI - Meteorological Drivers of Extremes in Daily Stem Radius Variations of Beech, Oak, and Pine in Northeastern Germany: An Event Coincidence Analysis. AB - Observed recent and expected future increases in frequency and intensity of climatic extremes in central Europe may pose critical challenges for domestic tree species. Continuous dendrometer recordings provide a valuable source of information on tree stem radius variations, offering the possibility to study a tree's response to environmental influences at a high temporal resolution. In this study, we analyze stem radius variations (SRV) of three domestic tree species (beech, oak, and pine) from 2012 to 2014. We use the novel statistical approach of event coincidence analysis (ECA) to investigate the simultaneous occurrence of extreme daily weather conditions and extreme SRVs, where extremes are defined with respect to the common values at a given phase of the annual growth period. Besides defining extreme events based on individual meteorological variables, we additionally introduce conditional and joint ECA as new multivariate extensions of the original methodology and apply them for testing 105 different combinations of variables regarding their impact on SRV extremes. Our results reveal a strong susceptibility of all three species to the extremes of several meteorological variables. Yet, the inter-species differences regarding their response to the meteorological extremes are comparatively low. The obtained results provide a thorough extension of previous correlation-based studies by emphasizing on the timings of climatic extremes only. We suggest that the employed methodological approach should be further promoted in forest research regarding the investigation of tree responses to changing environmental conditions. PMID- 27375626 TI - Metabolic Fate of the Carboxyl Groups of Malate and Pyruvate and their Influence on delta(13)C of Leaf-Respired CO2 during Light Enhanced Dark Respiration. AB - The enhanced CO2 release of illuminated leaves transferred into darkness, termed "light enhanced dark respiration (LEDR)", is often associated with an increase in the carbon isotope ratio of the respired CO2 (delta(13)CLEDR). The latter has been hypothesized to result from different respiratory substrates and decarboxylation reactions in various metabolic pathways, which are poorly understood so far. To provide a better insight into the underlying metabolic processes of delta(13)CLEDR, we fed position-specific (13)C-labeled malate and pyruvate via the xylem stream to leaves of species with high and low delta(13)CLEDR values (Halimium halimifolium and Oxalis triangularis, respectively). During respective label application, we determined label-derived leaf (13)CO2 respiration using laser spectroscopy and the (13)C allocation to metabolic fractions during light-dark transitions. Our results clearly show that both carboxyl groups (C-1 and C-4 position) of malate similarly influence respiration and metabolic fractions in both species, indicating possible isotope randomization of the carboxyl groups of malate by the fumarase reaction. While C 2 position of pyruvate was only weakly respired, the species-specific difference in natural delta(13)CLEDR patterns were best reflected by the (13)CO2 respiration patterns of the C-1 position of pyruvate. Furthermore, (13)C label from malate and pyruvate were mainly allocated to amino and organic acid fractions in both species and only little to sugar and lipid fractions. In summary, our results suggest that respiration of both carboxyl groups of malate (via fumarase) by tricarboxylic acid cycle reactions or by NAD-malic enzyme influences delta(13)CLEDR. The latter supplies the pyruvate dehydrogenase reaction, which in turn determines natural delta(13)CLEDR pattern by releasing the C-1 position of pyruvate. PMID- 27375627 TI - Identification and Characterization of Five BAHD Acyltransferases Involved in Hydroxycinnamoyl Ester Metabolism in Chicory. AB - Chicory (Cichorium intybus) accumulates caffeic acid esters with important significance for human health. In this study, we aim at a better understanding of the biochemical pathway of these bioactive compounds. Detailed metabolic analysis reveals that C. intybus predominantly accumulates caftaric and chicoric acids in leaves, whereas isochlorogenic acid (3,5-diCQA) was almost exclusively accumulated in roots. Chlorogenic acid (3-CQA) was equally distributed in all organs. Interestingly, distribution of the four compounds was related to leaf age. Induction with methyljasmonate (MeJA) of root cell suspension cultures results in an increase of 3-CQA and 3,5-diCQA contents. Expressed sequence tag libraries were screened using members of the BAHD family identified in Arabidopsis and tobacco as baits. The full-length cDNAs of five genes were isolated. Predicted amino acid sequence analyses revealed typical features of BAHD family members. Biochemical characterization of the recombinant proteins expressed in Escherichia coli showed that two genes encode HCTs (hydroxycinnamoyl CoA:shikimate/quinate hydroxycinnamoyltransferases, HCT1 and HCT2) whereas, three genes encode HQTs (hydroxycinnamoyl-CoA:quinate hydroxycinnamoyltransferases, HQT1, HQT2, and HQT3). These results totally agreed with the phylogenetic analysis done with the predicted amino acid sequences. Quantitative real-time polymerase chain reaction analysis of gene expression indicated that HQT3, HCT1, and HCT2 might be more directly associated with CQA accumulation in cell culture in response to MeJA elicitation. Transient expression of HCT1 and HQT1 in tobacco resulted in a higher production of 3-CQA. All together these data confirm the involvement of functionally redundant genes in 3-CQA and related compound synthesis in the Asteraceae family. PMID- 27375628 TI - 3D Surface Reconstruction of Plant Seeds by Volume Carving: Performance and Accuracies. AB - We describe a method for 3D reconstruction of plant seed surfaces, focusing on small seeds with diameters as small as 200 MUm. The method considers robotized systems allowing single seed handling in order to rotate a single seed in front of a camera. Even though such systems feature high position repeatability, at sub millimeter object scales, camera pose variations have to be compensated. We do this by robustly estimating the tool center point from each acquired image. 3D reconstruction can then be performed by a simple shape-from-silhouette approach. In experiments we investigate runtimes, theoretically achievable accuracy, experimentally achieved accuracy, and show as a proof of principle that the proposed method is well sufficient for 3D seed phenotyping purposes. PMID- 27375629 TI - Metabolomic and Proteomic Profiles Reveal the Dynamics of Primary Metabolism during Seed Development of Lotus (Nelumbo nucifera). AB - Sacred lotus (Nelumbo nucifera) belongs to the Nelumbonaceae family. Its seeds are widely consumed in Asian countries as snacks or even medicine. Besides the market value, lotus seed also plays a crucial role in the lotus life cycle. Consequently, it is essential to gain a comprehensive understanding of the development of lotus seed. During its development, lotus seed undergoes cell division, expansion, reserve accumulation, desiccation, and maturation phases. We observed morphological and biochemical changes from 10 to 25 days after pollination (DAP) which corresponded to the reserve synthesis and accumulation phase. The volume of the seed expanded until 20 DAP with the color of the seed coat changing from yellow-green to dark green and gradually fading again. Starch and protein rapidly accumulated from 15 to 20 DAP. To further reveal metabolic adaptation, primary metabolites and proteins profiles were obtained using mass spectrometry based platforms. Metabolites and enzymes involved in sugar metabolism, glycolysis, TCA cycle and amino acid metabolism showed sequential dynamics enabling the clear separation of the different metabolic states during lotus seed development. The integration of the data revealed a highly significant metabolic switch at 15 DAP going through a transition of metabolically highly active tissue to the preparation of storage tissue. The results provide a reference data set for the evaluation of primary metabolism during lotus seed development. PMID- 27375630 TI - Effects of Spatial Patch Arrangement and Scale of Covarying Resources on Growth and Intraspecific Competition of a Clonal Plant. AB - Spatial heterogeneity in two co-variable resources such as light and water availability is common and can affect the growth of clonal plants. Several studies have tested effects of spatial heterogeneity in the supply of a single resource on competitive interactions of plants, but none has examined those of heterogeneous distribution of two co-variable resources. In a greenhouse experiment, we grew one (without intraspecific competition) or nine isolated ramets (with competition) of a rhizomatous herb Iris japonica under a homogeneous environment and four heterogeneous environments differing in patch arrangement (reciprocal and parallel patchiness of light and soil water) and patch scale (large and small patches of light and water). Intraspecific competition significantly decreased the growth of I. japonica, but at the whole container level there were no significant interaction effects of competition by spatial heterogeneity or significant effect of heterogeneity on competitive intensity. Irrespective of competition, the growth of I. japonica in the high and the low water patches did not differ significantly in the homogeneous treatments, but it was significantly larger in the high than in the low water patches in the heterogeneous treatments with large patches. For the heterogeneous treatments with small patches, the growth of I. japonica was significantly larger in the high than in the low water patches in the presence of competition, but such an effect was not significant in the absence of competition. Furthermore, patch arrangement and patch scale significantly affected competitive intensity at the patch level. Therefore, spatial heterogeneity in light and water supply can alter intraspecific competition at the patch level and such effects depend on patch arrangement and patch scale. PMID- 27375631 TI - Is Wortmannin-Induced Reorganization of the trans-Golgi Network the Key to Explain Charasome Formation? AB - Wortmannin, a fungal metabolite and an inhibitor of phosphatidylinositol-3 (PI3) and phosphatidylinositol-4 (PI4) kinases, is widely used for the investigation and dissection of vacuolar trafficking routes and for the identification of proteins located at multivesicular bodies (MVBs). In this study, we applied wortmannin on internodal cells of the characean green alga Chara australis. Wortmannin was used at concentrations of 25 and 50 MUM which, unlike in other cells, arrested neither constitutive, nor wounding-induced endocytosis via coated vesicles. Wortmannin caused the formation of "mixed compartments" consisting of MVBs and membranous tubules which were probably derived from the trans-Golgi network (TGN) and within these compartments MVBs fused into larger organelles. Most interestingly, wortmannin also caused pronounced changes in the morphology of the TGNs. After transient hypertrophy, the TGNs lost their coat and formed compact, three-dimensional meshworks of anastomosing tubules containing a central core. These meshworks had a size of up to 4 MUm and a striking resemblance to charasomes, which are convoluted plasma membrane domains, and which serve to increase the area available for transporters. Our findings indicate that similar mechanisms are responsible for the formation of charasomes and the wortmannin induced reorganization of the TGN. We hypothesize that both organelles grow because of a disturbance of clathrin-dependent membrane retrieval due to inhibition of PI3 and/or PI4 kinases. This leads to local inhibition of clathrin mediated endocytosis during charasome formation in untreated cells and to inhibition of vesicle release from the TGN in wortmannin-treated cells, respectively. The morphological resemblance between charasomes and wortmannin modified TGN compartments suggests that homologous proteins are involved in membrane curvature and organelle architecture. PMID- 27375632 TI - Genomic Tools in Cowpea Breeding Programs: Status and Perspectives. AB - Cowpea is one of the most important grain legumes in sub-Saharan Africa (SSA). It provides strong support to the livelihood of small-scale farmers through its contributions to their nutritional security, income generation and soil fertility enhancement. Worldwide about 6.5 million metric tons of cowpea are produced annually on about 14.5 million hectares. The low productivity of cowpea is attributable to numerous abiotic and biotic constraints. The abiotic stress factors comprise drought, low soil fertility, and heat while biotic constraints include insects, diseases, parasitic weeds, and nematodes. Cowpea farmers also have limited access to quality seeds of improved varieties for planting. Some progress has been made through conventional breeding at international and national research institutions in the last three decades. Cowpea improvement could also benefit from modern breeding methods based on molecular genetic tools. A number of advances in cowpea genetic linkage maps, and quantitative trait loci associated with some desirable traits such as resistance to Striga, Macrophomina, Fusarium wilt, bacterial blight, root-knot nematodes, aphids, and foliar thrips have been reported. An improved consensus genetic linkage map has been developed and used to identify QTLs of additional traits. In order to take advantage of these developments single nucleotide polymorphism (SNP) genotyping is being streamlined to establish an efficient workflow supported by genotyping support service (GSS)-client interactions. About 1100 SNPs mapped on the cowpea genome were converted by LGC Genomics to KASP assays. Several cowpea breeding programs have been exploiting these resources to implement molecular breeding, especially for MARS and MABC, to accelerate cowpea variety improvement. The combination of conventional breeding and molecular breeding strategies, with workflow managed through the CGIAR breeding management system (BMS), promises an increase in the number of improved varieties available to farmers, thereby boosting cowpea production and productivity in SSA. PMID- 27375633 TI - The Potential of Hyperspectral Patterns of Winter Wheat to Detect Changes in Soil Microbial Community Composition. AB - Reliable information on soil status and crop health is crucial for detecting and mitigating disasters like pollution or minimizing impact from soil-borne diseases. While infestation with an aggressive soil pathogen can be detected via reflected light spectra, it is unknown to what extent hyperspectral reflectance could be used to detect overall changes in soil biodiversity. We tested the hypotheses that spectra can be used to (1) separate plants growing with microbial communities from different farms; (2) to separate plants growing in different microbial communities due to different land use; and (3) separate plants according to microbial species loss. We measured hyperspectral reflectance patterns of winter wheat plants growing in sterilized soils inoculated with microbial suspensions under controlled conditions. Microbial communities varied due to geographical distance, land use and microbial species loss caused by serial dilution. After 3 months of growth in the presence of microbes from the two different farms plant hyperspectral reflectance patterns differed significantly from each other, while within farms the effects of land use via microbes on plant reflectance spectra were weak. Species loss via dilution on the other hand affected a number of spectral indices for some of the soils. Spectral reflectance can be indicative of differences in microbial communities, with the Renormalized Difference Vegetation Index the most common responding index. Also, a positive correlation was found between the Normalized Difference Vegetation Index and the bacterial species richness, which suggests that plants perform better with higher microbial diversity. There is considerable variation between the soil origins and currently it is not possible yet to make sufficient reliable predictions about the soil microbial community based on the spectral reflectance. We conclude that measuring plant hyperspectral reflectance has potential for detecting changes in microbial communities yet due to its sensitivity high replication is necessary and a strict sampling design to exclude other 'noise' factors. PMID- 27375634 TI - WRKY Transcription Factors: Molecular Regulation and Stress Responses in Plants. AB - Plants in their natural habitat have to face multiple stresses simultaneously. Evolutionary adaptation of developmental, physiological, and biochemical parameters give advantage over a single window of stress but not multiple. On the other hand transcription factors like WRKY can regulate diverse responses through a complicated network of genes. So molecular orchestration of WRKYs in plant may provide the most anticipated outcome of simultaneous multiple responses. Activation or repression through W-box and W-box like sequences is regulated at transcriptional, translational, and domain level. Because of the tight regulation involved in specific recognition and binding of WRKYs to downstream promoters, they have become promising candidate for crop improvement. Epigenetic, retrograde and proteasome mediated regulation enable WRKYs to attain the dynamic cellular homeostatic reprograming. Overexpression of several WRKYs face the paradox of having several beneficial affects but with some unwanted traits. These overexpression-associated undesirable phenotypes need to be identified and removed for proper growth, development and yeild. Taken together, we have highlighted the diverse regulation and multiple stress response of WRKYs in plants along with the future prospects in this field of research. PMID- 27375636 TI - Improving Rice Zinc Biofortification Success Rates Through Genetic and Crop Management Approaches in a Changing Environment. AB - Though rice is the predominant source of energy and micronutrients for more than half of the world population, it does not provide enough zinc (Zn) to match human nutritional requirements. Moreover, climate change, particularly rising atmospheric carbon dioxide concentration, reduces the grain Zn concentration. Therefore, rice biofortification has been recognized as a key target to increase the grain Zn concentration to address global Zn malnutrition. Major bottlenecks for Zn biofortification in rice are identified as low Zn uptake, transport and loading into the grain; however, environmental and genetic contributions to grain Zn accumulation in rice have not been fully explored. In this review, we critically analyze the key genetic, physiological and environmental factors that determine Zn uptake, transport and utilization in rice. We also explore the genetic diversity of rice germplasm to develop new genetic tools for Zn biofortification. Lastly, we discuss the strategic use of Zn fertilizer for developing biofortified rice. PMID- 27375637 TI - Plasticity in Vulnerability to Cavitation of Pinus canariensis Occurs Only at the Driest End of an Aridity Gradient. AB - Water availability has been considered one of the crucial drivers of species distribution. However, the increasing of temperatures and more frequent water shortages could overcome the ability of long-lived species to cope with rapidly changing conditions. Growth and survival of natural populations adapted to a given site, transferred and tested in other environments as part of provenance trials, can be interpreted as a simulation of ambient changes at the original location. We compare the intraspecific variation and the relative contribution of plasticity to adaptation of key functional traits related to drought resistance: vulnerability to cavitation, efficiency of the xylem to conduct water and biomass allocation. We use six populations of Canary Island pine growing in three provenance trials (wet, dry, and xeric). We found that the variability for hydraulic traits was largely due to phenotypic plasticity, whereas, genetic variation was limited and almost restricted to hydraulic safety traits and survival. Trees responded to an increase in climate dryness by lowering growth, and increasing leaf-specific hydraulic conductivity by means of increasing the Huber value. Vulnerability to cavitation only showed a plastic response in the driest provenance trial located in the ecological limit of the species. This trait was more tightly correlated with annual precipitation, drought length, and temperature oscillation at the origin of the populations than hydraulic efficiency or the Huber value. Vulnerability to cavitation was directly related to survival in the dry and the xeric provenance trials, illustrating its importance in determining drought resistance. In a new climatic scenario where more frequent and intense droughts are predicted, the magnitude of extreme events together with the fact that plasticity of cavitation resistance is only shown in the very dry limit of the species could hamper the capacity to adapt and buffer against environmental changes of some populations growing in dry locations. PMID- 27375635 TI - Exploiting Phenylpropanoid Derivatives to Enhance the Nutraceutical Values of Cereals and Legumes. AB - Phenylpropanoids are a diverse chemical class with immense health benefits that are biosynthesized from the aromatic amino acid L-phenylalanine. This article reviews the progress for accessing variation in phenylpropanoids in germplasm collections, the genetic and molecular basis of phenylpropanoid biosynthesis, and the development of cultivars dense in seed-phenylpropanoids. Progress is also reviewed on high-throughput assays, factors that influence phenylpropanoids, the site of phenylpropanoids accumulation in seed, Genotype * Environment interactions, and on consumer attitudes for the acceptance of staple foods rich in phenylpropanoids. A paradigm shift was noted in barley, maize, rice, sorghum, soybean, and wheat, wherein cultivars rich in phenylpropanoids are grown in Europe and North and Central America. Studies have highlighted some biological constraints that need to be addressed for development of high-yielding cultivars that are rich in phenylpropanoids. Genomics-assisted breeding is expected to facilitate rapid introgression into improved genetic backgrounds by minimizing linkage drag. More research is needed to systematically characterize germplasm pools for assessing variation to support crop genetic enhancement, and assess consumer attitudes to foods rich in phenylpropanoids. PMID- 27375638 TI - Identification of Circular RNAs from the Parental Genes Involved in Multiple Aspects of Cellular Metabolism in Barley. AB - RNA circularization made by head-to-tail back-splicing events is involved in the regulation of gene expression from transcriptional to post-translational levels. By exploiting RNA-Seq data and down-stream analysis, we shed light on the importance of circular RNAs in plants. The results introduce circular RNAs as novel interactors in the regulation of gene expression in plants and imply the comprehensiveness of this regulatory pathway by identifying circular RNAs for a diverse set of genes. These genes are involved in several aspects of cellular metabolism as hormonal signaling, intracellular protein sorting, carbohydrate metabolism and cell-wall biogenesis, respiration, amino acid biosynthesis, transcription and translation, and protein ubiquitination. Additionally, these parental loci of circular RNAs, from both nuclear and mitochondrial genomes, encode for different transcript classes including protein coding transcripts, microRNA, rRNA, and long non-coding/microprotein coding RNAs. The results shed light on the mitochondrial exonic circular RNAs and imply the importance of circular RNAs for regulation of mitochondrial genes. Importantly, we introduce circular RNAs in barley and elucidate their cellular-level alterations across tissues and in response to micronutrients iron and zinc. In further support of circular RNAs' functional roles in plants, we report several cases where fluctuations of circRNAs do not correlate with the levels of their parental-loci encoded linear transcripts. PMID- 27375639 TI - Root Foraging Performance and Life-History Traits. AB - Plants use their roots to forage for nutrients in heterogeneous soil environments, but different plant species vastly differ in the intensity of foraging they perform. This diversity suggests the existence of constraints on foraging at the species level. We therefore examined the relationships between the intensity of root foraging and plant body traits across species in order to estimate the degree of coordination between plant body traits and root foraging as a form of plant behavior. We cultivated 37 perennial herbaceous Central European species from open terrestrial habitats in pots with three different spatial gradients of nutrient availability (steep, shallow, and no gradient). We assessed the intensity of foraging as differences in root placement inside pots with and without a spatial gradient of resource supply. For the same set of species, we retrieved data about body traits from available databases: maximum height at maturity, mean area of leaf, specific leaf area, shoot lifespan, ability to self-propagate clonally, maximal lateral spread (in clonal plants only), realized vegetative growth in cultivation, and realized seed regeneration in cultivation. Clonal plants and plants with extensive vegetative growth showed considerably weaker foraging than their non-clonal or slow-growing counterparts. There was no phylogenetic signal in the amount of expressed root foraging intensity. Since clonal plants foraged less than non-clonals and foraging intensity did not seem to be correlated with species phylogeny, we hypothesize that clonal growth itself (i.e., the ability to develop at least partly self sustaining ramets) may be an answer to soil heterogeneity. Whereas unitary plants use roots as organs specialized for both resource acquisition and transport to overcome spatial heterogeneity in resource supply, clonal plants separate these two functions. Becoming a clonal plant allows higher specialization at the organ level, since a typical clonal plant can be viewed as a network of self sustainable harvesting units connected together with specialized high-throughput connection organs. This may be an effective alternative for coping with spatial heterogeneity in resource availability. PMID- 27375640 TI - Validation of Reference Genes for RT-qPCR Studies of Gene Expression in Preharvest and Postharvest Longan Fruits under Different Experimental Conditions. AB - Reverse transcription quantitative PCR (RT-qPCR) as the accurate and sensitive method is use for gene expression analysis, but the veracity and reliability result depends on whether select appropriate reference gene or not. To date, several reliable reference gene validations have been reported in fruits trees, but none have been done on preharvest and postharvest longan fruits. In this study, 12 candidate reference genes, namely, CYP, RPL, GAPDH, TUA, TUB, Fe-SOD, Mn-SOD, Cu/Zn-SOD, 18SrRNA, Actin, Histone H3, and EF-1a, were selected. Expression stability of these genes in 150 longan samples was evaluated and analyzed using geNorm and NormFinder algorithms. Preharvest samples consisted of seven experimental sets, including different developmental stages, organs, hormone stimuli (NAA, 2,4-D, and ethephon) and abiotic stresses (bagging and girdling with defoliation). Postharvest samples consisted of different temperature treatments (4 and 22 degrees C) and varieties. Our findings indicate that appropriate reference gene(s) should be picked for each experimental condition. Our data further showed that the commonly used reference gene Actin does not exhibit stable expression across experimental conditions in longan. Expression levels of the DlACO gene, which is a key gene involved in regulating fruit abscission under girdling with defoliation treatment, was evaluated to validate our findings. In conclusion, our data provide a useful framework for choice of suitable reference genes across different experimental conditions for RT-qPCR analysis of preharvest and postharvest longan fruits. PMID- 27375641 TI - Quantitative Wood Anatomy-Practical Guidelines. AB - Quantitative wood anatomy analyzes the variability of xylem anatomical features in trees, shrubs, and herbaceous species to address research questions related to plant functioning, growth, and environment. Among the more frequently considered anatomical features are lumen dimensions and wall thickness of conducting cells, fibers, and several ray properties. The structural properties of each xylem anatomical feature are mostly fixed once they are formed, and define to a large extent its functionality, including transport and storage of water, nutrients, sugars, and hormones, and providing mechanical support. The anatomical features can often be localized within an annual growth ring, which allows to establish intra-annual past and present structure-function relationships and its sensitivity to environmental variability. However, there are many methodological challenges to handle when aiming at producing (large) data sets of xylem anatomical data. Here we describe the different steps from wood sample collection to xylem anatomical data, provide guidance and identify pitfalls, and present different image-analysis tools for the quantification of anatomical features, in particular conducting cells. We show that each data production step from sample collection in the field, microslide preparation in the lab, image capturing through an optical microscope and image analysis with specific tools can readily introduce measurement errors between 5 and 30% and more, whereby the magnitude usually increases the smaller the anatomical features. Such measurement errors-if not avoided or corrected-may make it impossible to extract meaningful xylem anatomical data in light of the rather small range of variability in many anatomical features as observed, for example, within time series of individual plants. Following a rigid protocol and quality control as proposed in this paper is thus mandatory to use quantitative data of xylem anatomical features as a powerful source for many research topics. PMID- 27375642 TI - Lights Off for Arbuscular Mycorrhiza: On Its Symbiotic Functioning under Light Deprivation. AB - Plants are often exposed to shade over different time scales and this may substantially affect not only their own growth, but also development and functioning of the energetically dependent organisms. Among those, the root symbionts such as arbuscular mycorrhizal (AM) fungi and rhizobia represent particularly important cases-on the one hand, they consume a significant share of plant carbon (C) budget and, on the other, they generate a number of important nutritional feedbacks on their plant hosts, often resulting in a net positive effect on their host growth and/or fitness. Here we discuss our previous results comparing mycorrhizal performance under different intensities and durations of shade (Konvalinkova et al., 2015) in a broader context of previously published literature. Additionally, we review publicly available knowledge on the root colonization and mycorrhizal growth responses in AM plants under light deprivation. Experimental evidence shows that sudden and intensive decrease of light availability to a mycorrhizal plant triggers rapid deactivation of phosphorus transfer from the AM fungus to the plant already within a few days, implying active and rapid response of the AM fungus to the energetic status of its plant host. When AM plants are exposed to intensive shading on longer time scales (weeks to months), positive mycorrhizal growth responses (MGR) are often decreasing and may eventually become negative. This is most likely due to the high C cost of the symbiosis relative to the C availability, and failure of plants to fully compensate for the fungal C demand under low light. Root colonization by AM fungi often declines under low light intensities, although the active role of plants in regulating the extent of root colonization has not yet been unequivocally demonstrated. Quantitative information on the rates and dynamics of C transfer from the plant to the fungus is mostly missing, as is the knowledge on the involved molecular mechanisms. Therefore, these subjects deserve particular attention in the future. PMID- 27375644 TI - Non-matrix Matched Glass Disk Calibration Standards Improve XRF Micronutrient Analysis of Wheat Grain across Five Laboratories in India. AB - Within the HarvestPlus program there are many collaborators currently using X-Ray Fluorescence (XRF) spectroscopy to measure Fe and Zn in their target crops. In India, five HarvestPlus wheat collaborators have laboratories that conduct this analysis and their throughput has increased significantly. The benefits of using XRF are its ease of use, minimal sample preparation and high throughput analysis. The lack of commercially available calibration standards has led to a need for alternative calibration arrangements for many of the instruments. Consequently, the majority of instruments have either been installed with an electronic transfer of an original grain calibration set developed by a preferred lab, or a locally supplied calibration. Unfortunately, neither of these methods has been entirely successful. The electronic transfer is unable to account for small variations between the instruments, whereas the use of a locally provided calibration set is heavily reliant on the accuracy of the reference analysis method, which is particularly difficult to achieve when analyzing low levels of micronutrient. Consequently, we have developed a calibration method that uses non matrix matched glass disks. Here we present the validation of this method and show this calibration approach can improve the reproducibility and accuracy of whole grain wheat analysis on 5 different XRF instruments across the HarvestPlus breeding program. PMID- 27375643 TI - Haplotypes of the TaGS5-A1 Gene Are Associated with Thousand-Kernel Weight in Chinese Bread Wheat. AB - In previous work, we cloned TaGS5 gene and found the association of TaGS5-A1 alleles with agronomic traits. In this study, the promoter sequence of the TaGS5 A1 gene was isolated from bread wheat. Sequencing results revealed that a G insertion was found in position -1925 bp of the TaGS5-A1 gene (Reference to ATG), which occurred in the Sp1 domain of the promoter sequence. Combined with previous single nucleotide polymorphism (SNP) in the TaGS5-A1 exon sequence, four genotypes were formed at the TaGS5-A1 locus and were designated as TaGS5-A1a-a, TaGS5-A1a-b, TaGS5-A1b-a, and TaGS5-A1b-b, respectively. Analysis of the association of TaGS5-A1 alleles with agronomic traits indicated that cultivars with the TaGS5-A1a-b allele possessed significantly higher thousand-kernel weight (TKW) and lower plant height than cultivars with the TaGS5-A1a-a allele, and cultivars with the TaGS5-A1b-b allele showed higher TKW than cultivars with the TaGS5-A1b-a allele. The differences of these traits between the TaGS5-A1a-a and TaGS5-A1a-b alleles were larger than those of the TaGS5-A1b-a and TaGS5-A1b-b alleles, suggesting that the -1925G insertion plays the more important role in TaGS5-A1a genotypes than in TaGS5-A1b genotypes. qRT-PCR indicated that TaGS5-A1b b possessed the significantly highest expression level among four TaGS5-A1 haplotypes in mature seeds and further showed a significantly higher expression level than TaGS5-A1b-a at five different developmental stages of the seeds, suggesting that high expression of TaGS5-A1 was positively associated with high TKW in bread wheat. This study could provide a relatively superior genotype in view of TKW in wheat breeding programs and could also provide important information for dissection of the regulatory mechanism of the yield-related traits. PMID- 27375645 TI - Field-Grown Grapevine Berries Use Carotenoids and the Associated Xanthophyll Cycles to Acclimate to UV Exposure Differentially in High and Low Light (Shade) Conditions. AB - Light quantity and quality modulate grapevine development and influence berry metabolic processes. Here we studied light as an information signal for developing and ripening grape berries. A Vitis vinifera Sauvignon Blanc field experiment was used to identify the impacts of UVB on core metabolic processes in the berries under both high light (HL) and low light (LL) microclimates. The primary objective was therefore to identify UVB-specific responses on berry processes and metabolites and distinguish them from those responses elicited by variations in light incidence. Canopy manipulation at the bunch zone via early leaf removal, combined with UVB-excluding acrylic sheets installed over the bunch zones resulted in four bunch microclimates: (1) HL (control); (2) LL (control); (3) HL with UVB attenuation and (4) LL with UVB attenuation. Metabolite profiles of three berry developmental stages showed predictable changes to known UV responsive compound classes in a typical UV acclimation (versus UV damage) response. Interestingly, the berries employed carotenoids and the associated xanthophyll cycles to acclimate to UV exposure and the berry responses differed between HL and LL conditions, particularly in the developmental stages where berries are still photosynthetically active. The developmental stage of the berries was an important factor to consider in interpreting the data. The green berries responded to the different exposure and/or UVB attenuation signals with metabolites that indicate that the berries actively managed its metabolism in relation to the exposure levels, displaying metabolic plasticity in the photosynthesis-related metabolites. Core processes such as photosynthesis, photo inhibition and acclimation were maintained by differentially modulating metabolites under the four treatments. Ripe berries also responded metabolically to the light quality and quantity, but mostly formed compounds (volatiles and polyphenols) that have direct antioxidant and/or "sunscreening" abilities. The data presented for the green berries and those for the ripe berries conform to what is known for UVB and/or light stress in young, active leaves and older, senescing tissues respectively and provide scope for further evaluation of the sink/source status of fruits in relation to photosignalling and/or stress management. PMID- 27375646 TI - Genetic Diversity and Elite Allele Mining for Grain Traits in Rice (Oryza sativa L.) by Association Mapping. AB - Mining elite alleles for grain size and weight is of importance for the improvement of cultivated rice and selection for market demand. In this study, association mapping for grain traits was performed on a selected sample of 628 rice cultivars using 262 SSRs. Grain traits were evaluated by grain length (GL), grain width (GW), grain thickness (GT), grain length to width ratio (GL/GW), and 1000-grain weight (TGW) in 2013 and 2014. Our result showed abundant phenotypic and genetic diversities found in the studied population. In total, 2953 alleles were detected with an average of 11.3 alleles per locus. The population was divided into seven subpopulations and the levels of linkage disequilibrium (LD) ranged from 34 to 84 cM. Genome-wide association mapping detected 10 marker trait association (MTAs) loci for GL, 1MTAs locus for GW, 7 MTAs loci for GT, 3 MTAs loci for GL/GW, and 1 MTAs locus for TGW. Twenty-nine, 2, 10, 5, and 3 elite alleles were found for the GL, GW, GT, GL/GW, and TGW, respectively. Optimal cross designs were predicted for improving the target traits. The accessions containing elite alleles for grain traits mined in this study could be used for breeding rice cultivars and cloning the candidate genes. PMID- 27375647 TI - Expression Profiles, Characterization and Function of HbTCTP in Rubber Tree (Hevea brasiliensis). AB - As a highly conserved protein, the translationally controlled tumor protein (TCTP) carries out vital roles in various life processes. In rubber tree, two TCTP genes, HbTCTP and HbTCTP1, were cloned, but only HbTCTP1 was studied in details. In this study, cis-acting regulatory elements, expression patterns, subcellular localization, interacting proteins, and antioxidant activity of HbTCTP were systematically analyzed. Besides the common cis-acting regulatory elements, HbTCTP promoter also harbored various known cis-elements that respond to hormone/stresses. Being consistent with the aforementioned results, HbTCTP was regulated by drought, low temperature, high salt, ethylene (ET), wounding, H2O2, and methyl jasmonate (MeJA) treatments. HbTCTP was expressed throughout different tissues and developmental stages of leaves. In addition, HbTCTP was associated with tapping panel dryness (TPD). HbTCTP was localized in the membrane, cytoplasm and the nucleus, and interacted with four proteins rubber elongation factor (REF), 17.5 kDa heat shock family protein, annexin, and REF-like stress related protein 1. Being similar to HbTCTP1, HbTCTP also indicated antioxidant activity in metal-catalyzed oxidation (MCO) system. Our results are useful for further understanding the molecular characterization and expression profiles of HbTCTP, but also lay a solid foundation for elucidating the function of HbTCTP in rubber tree. PMID- 27375648 TI - Quinoa Seed Quality Response to Sodium Chloride and Sodium Sulfate Salinity. AB - Quinoa (Chenopodium quinoa Willd.) is an Andean crop with an edible seed that both contains high protein content and provides high quality protein with a balanced amino acid profile in embryonic tissues. Quinoa is a halophyte adapted to harsh environments with highly saline soil. In this study, four quinoa varieties were grown under six salinity treatments and two levels of fertilization, and then evaluated for quinoa seed quality characteristics, including protein content, seed hardness, and seed density. Concentrations of 8, 16, and 32 dS m(-1) of NaCl and Na2SO4, were applied to the soil medium across low (1 g N, 0.29 g P, 0.29 g K per pot) and high (3 g N, 0.85 g P, 0.86 g K per pot) fertilizer treatments. Seed protein content differed across soil salinity treatments, varieties, and fertilization levels. Protein content of quinoa grown under salinized soil ranged from 13.0 to 16.7%, comparable to that from non saline conditions. NaCl and Na2SO4 exhibited different impacts on protein content. Whereas the different concentrations of NaCl did not show differential effects on protein content, the seed from 32 dS m(-1) Na2SO4 contained the highest protein content. Seed hardness differed among varieties, and was moderately influenced by salinity level (P = 0.09). Seed density was affected significantly by variety and Na2SO4 concentration, but was unaffected by NaCl concentration. The samples from 8 dS m(-1) Na2SO4 soil had lower density (0.66 g/cm(3)) than those from 16 dS m(-1) and 32 dS m(-1) Na2SO4, 0.74 and 0.72g/cm(3), respectively. This paper identifies changes in critical seed quality traits of quinoa as influenced by soil salinity and fertility, and offers insights into variety response and choice across different abiotic stresses in the field environment. PMID- 27375650 TI - Wheat Phenological Development and Growth Studies As Affected by Drought and Late Season High Temperature Stress under Arid Environment. AB - This study evaluates the potential for adaptability and tolerance of wheat genotypes (G) to an arid environment. We examined the influence of drought stress (DS) (100, 75, and 50% field capacity), planting times (PT) (16-November, 01 December, 16-December and 01-January), and G (Yocoro Rojo, FKAU-10, Faisalabad 08, and Galaxy L-7096) on phenological development, growth indices, grain yield, and water use efficiency of drip-irrigated wheat. Development measured at five phenological growth stages (GS) (tillering, jointing, booting, heading, and maturity) and growth indices 30, 45, 60, and 75 days after sowing (DAS) were also correlated with final grain yield. Tillering occurred earlier in DS plots, to a maximum of 31 days. Days to complete 50% heading and physiological crop maturity were the most susceptible GS that denoted 31-72% reduction in number of days to complete these GS at severe DS. Wheat G grown with severe DS had the shortest grain filling duration. Genotype Fsd-08 presented greater adaptability to studied arid climate and recorded 31, 35, and 38% longer grain filling period as compared with rest of the G at 100-50% field capacity respectively. December sowing mitigated the drought and delayed planting effects by producing superior growth and yield (2162 kg ha(-1)) at severe DS. Genotypes Fsd-08 and L-7096 attained the minimum plant height (36 cm) and the shortest growth cycle (76 days) for January planting with 50% field capacity. At severe DS leaf area index, dry matter accumulation, crop growth rate and net assimilation rate were decreased by 67, 57, 34, and 38% as compared to non-stressed plots. Genotypes Fsd-08 and F-10 were the superior ones and secured 14-17% higher grain yield than genotype YR for severely stressed plots. The correlation between crop growth indices and grain yield depicted the highest value (0.58-0.71) at 60-75 DAS. So the major contribution of these growth indices toward grain yield was at the start of reproductive phase. It's clear that booting and grain filling are the most sensitive GS that are severely affected by both drought and delay in planting. PMID- 27375651 TI - Ecophysiological Modeling of Grapevine Water Stress in Burgundy Terroirs by a Machine-Learning Approach. AB - In a climate change scenario, successful modeling of the relationships between plant-soil-meteorology is crucial for a sustainable agricultural production, especially for perennial crops. Grapevines (Vitis vinifera L. cv Chardonnay) located in eight experimental plots (Burgundy, France) along a hillslope were monitored weekly for 3 years for leaf water potentials, both at predawn (Psipd) and at midday (Psistem). The water stress experienced by grapevine was modeled as a function of meteorological data (minimum and maximum temperature, rainfall) and soil characteristics (soil texture, gravel content, slope) by a gradient boosting machine. Model performance was assessed by comparison with carbon isotope discrimination (delta(13)C) of grape sugars at harvest and by the use of a test set. The developed models reached outstanding prediction performance (RMSE < 0.08 MPa for Psistem and < 0.06 MPa for Psipd), comparable to measurement accuracy. Model predictions at a daily time step improved correlation with delta(13)C data, respect to the observed trend at a weekly time scale. The role of each predictor in these models was described in order to understand how temperature, rainfall, soil texture, gravel content and slope affect the grapevine water status in the studied context. This work proposes a straight-forward strategy to simulate plant water stress in field condition, at a local scale; to investigate ecological relationships in the vineyard and adapt cultural practices to future conditions. PMID- 27375649 TI - Nod Factor Effects on Root Hair-Specific Transcriptome of Medicago truncatula: Focus on Plasma Membrane Transport Systems and Reactive Oxygen Species Networks. AB - Root hairs are involved in water and nutrient uptake, and thereby in plant autotrophy. In legumes, they also play a crucial role in establishment of rhizobial symbiosis. To obtain a holistic view of Medicago truncatula genes expressed in root hairs and of their regulation during the first hours of the engagement in rhizobial symbiotic interaction, a high throughput RNA sequencing on isolated root hairs from roots challenged or not with lipochitooligosaccharides Nod factors (NF) for 4 or 20 h was carried out. This provided a repertoire of genes displaying expression in root hairs, responding or not to NF, and specific or not to legumes. In analyzing the transcriptome dataset, special attention was paid to pumps, transporters, or channels active at the plasma membrane, to other proteins likely to play a role in nutrient ion uptake, NF electrical and calcium signaling, control of the redox status or the dynamic reprogramming of root hair transcriptome induced by NF treatment, and to the identification of papilionoid legume-specific genes expressed in root hairs. About 10% of the root hair expressed genes were significantly up- or down regulated by NF treatment, suggesting their involvement in remodeling plant functions to allow establishment of the symbiotic relationship. For instance, NF induced changes in expression of genes encoding plasma membrane transport systems or disease response proteins indicate that root hairs reduce their involvement in nutrient ion absorption and adapt their immune system in order to engage in the symbiotic interaction. It also appears that the redox status of root hair cells is tuned in response to NF perception. In addition, 1176 genes that could be considered as "papilionoid legume-specific" were identified in the M. truncatula root hair transcriptome, from which 141 were found to possess an ortholog in every of the six legume genomes that we considered, suggesting their involvement in essential functions specific to legumes. This transcriptome provides a valuable resource to investigate root hair biology in legumes and the roles that these cells play in rhizobial symbiosis establishment. These results could also contribute to the long-term objective of transferring this symbiotic capacity to non-legume plants. PMID- 27375652 TI - Fighting Asian Soybean Rust. AB - Phakopsora pachyrhizi is a biotrophic fungus provoking SBR disease. SBR poses a major threat to global soybean production. Though several R genes provided soybean immunity to certain P. pachyrhizi races, the pathogen swiftly overcame this resistance. Therefore, fungicides are the only current means to control SBR. However, insensitivity to fungicides is soaring in P. pachyrhizi and, therefore, alternative measures are needed for SBR control. In this article, we discuss the different approaches for fighting SBR and their potential, disadvantages, and advantages over other measures. These encompass conventional breeding for SBR resistance, transgenic approaches, exploitation of transcription factors, secondary metabolites, and antimicrobial peptides, RNAi/HIGS, and biocontrol strategies. It seems that an integrating approach exploiting different measures is likely to provide the best possible means for the effective control of SBR. PMID- 27375653 TI - Stable Water Use Efficiency under Climate Change of Three Sympatric Conifer Species at the Alpine Treeline. AB - The ability of treeline associated conifers in the Central Alps to cope with recent climate warming and increasing CO2 concentration is still poorly understood. We determined tree ring stable carbon and oxygen isotope ratios of Pinus cembra, Picea abies, and Larix decidua trees from 1975 to 2010. Stable isotope ratios were compared with leaf level gas exchange measurements carried out in situ between 1979 and 2007. Results indicate that tree ring derived intrinsic water-use efficiency (iWUE) of P. cembra, P. abies and L. decidua remained constant during the last 36 years despite climate warming and rising atmospheric CO2. Temporal patterns in Delta(13)C and Delta(18)O mirrored leaf level gas exchange assessments, suggesting parallel increases of CO2-fixation and stomatal conductance of treeline conifer species. As at the study site soil water availability was not a limiting factor iWUE remained largely stable throughout the study period. The stability in iWUE was accompanied by an increase in basal area increment (BAI) suggesting that treeline trees benefit from both recent climate warming and CO2 fertilization. Finally, our results suggest that iWUE may not change species composition at treeline in the Austrian Alps due to similar ecophysiological responses to climatic changes of the three sympatric study species. PMID- 27375654 TI - Low Temperature Affects Stem Cell Maintenance in Brassica oleracea Seedlings. AB - Most of the above ground tissues in higher plants originate from stem cells located in the shoot apical meristem (SAM). Several plant species can suffer from spontaneous stem cell arrest resulting in lack of further shoot development. In Brassica oleracea this SAM arrest is known as blindness and occurs in an unpredictable manner leading to considerable economic losses for plant raisers and farmers. Detailed analyses of seedlings showed that stem cell arrest is triggered by low temperatures during germination. To induce this arrest reproducibly and to study the effect of the environment, an assay was developed. The role of genetic variation on the susceptibility to develop blind seedlings was analyzed by a quantitative genetic mapping approach, using seeds from a double haploid population from a cross between broccoli and Chinese kale, produced at three locations. The analysis revealed, besides an effect of the seed production location, a region on linkage group C3 associated with blindness sensitivity. A subsequent dynamic genome-wide transcriptome analysis resulted in the identification of around 3000 differentially expressed genes early after blindness induction. A large number of cell cycle genes were en masse induced early during the development of blindness, whereas shortly after, all were down regulated. This miss-regulation of core cell cycle genes is accompanied with a strong reduction of cells reaching the DNA replication phase. From the differentially expressed genes, 90 were located in the QTL region C3. Among them are two genes belonging to the MINICHROMOSOMAL MAINTENANCE gene family, known to be involved in DNA replication, a RETINOBLASTOMA-RELATED gene, a key regulator for cell cycle initiation, and several MutS homologs genes, involved in DNA repair. These genes are potential candidates for being involved in the development of blindness in Brassica oleracea sensitive genotypes. PMID- 27375655 TI - De novo Assembly and Characterization of the Fruit Transcriptome of Idesia polycarpa Reveals Candidate Genes for Lipid Biosynthesis. AB - Idesia polycarpa, is a valuable oilseed-producing tree of the Flacourtiaceae family that has the potential to fulfill edible oil production and is also a possible biofuel feedstock. The fruit is unique in that it contains both saturated and unsaturated lipids present in pericarp and seed, respectively. However, triglyceride synthesis and storage in tissues outside of the seeds has been poorly studied in previous researches. To gain insight into the unique properties of I. polycarpa fruit lipid synthesis, biochemical, and transcriptomic approaches were used to compare the lipid accumulation between pericarp and seed of the fruit. Lipid accumulation rates, final lipid content and composition were significantly different between two tissues. Furthermore, we described the annotated transcriptome assembly and differential gene expression analysis generated from the pericarp and seed tissues. The data allowed the identification of distinct candidate genes and reconstruction of lipid pathways, which may explain the differences of oil synthesis between the two tissues. The results may be useful for engineering alternative pathways for lipid production in non-seed or vegetative tissues. PMID- 27375656 TI - Marker-Trait Association for Biomass Yield of Potential Bio-fuel Feedstock Miscanthus sinensis from Southwest China. AB - As a great potential bio-fuel feedstock, the genus Miscanthus has been widely studied around the world, especially Miscanthus * giganteus owing to its high biomass yield in Europe and North America. However, the narrow genetic basis and sterile characteristics of M. * giganteus have become a limitation for utilization and adaptation to extreme climate conditions. In this study, we focused on one of the progenitors of M. * giganteus, Miscanthus sinensis, which was originally distributed in East Asia with abundant genetic resources and comparable biomass yield potential to M. * giganteus in some areas. A collection of 138 individuals was selected for conducting a 3-year trial of biomass production and analyzed by using 104 pairs of SRAP, ISAP, and SSR primers for genetic diversity as well as marker-trait association. Significant differences in biomass yield and related traits were observed among individuals. Tiller number, fresh biomass yield per plant and dry biomass yield per plant had a high level of phenotypic variation among individuals and the coefficient of variation were all above 40% in 2011, 2012, and 2013. The majority of the traits had a significant correlation with the biomass yield except for the length and width of flag leaves. Plant height was a highly stable trait correlated with biomass yield. A total of 1059 discernible loci were detected by markers across individuals. The population structure (Q) and cluster analyses identified three subpopulations in the collection and family relative kinship (K) represented high gene flow among M. sinensis populations from Southwest China. Model testing identified that Q+K was the best model for describing the associations between the markers and traits, compared to the simple linear, Q or K model. Using the Q+K model, 12 significant associations (P < 0.001) were identified including four markers with plant height and one with biomass yield. Such associations would serve an efficient tool for an early selection of M. sinensis and facilitate a genetic improvement of biomass yield for this species. PMID- 27375657 TI - Extensive Natural Variation in Arabidopsis Seed Mucilage Structure. AB - Hydrated Arabidopsis thaliana seeds are coated by a gelatinous layer called mucilage, which is mainly composed of cell wall polysaccharides. Since mucilage is rich in pectin, its architecture can be visualized with the ruthenium red (RR) dye. We screened the seeds of around 280 Arabidopsis natural accessions for variation in mucilage structure, and identified a large number of novel variants that differed from the Col-0 wild-type. Most of the accessions released smaller RR-stained capsules compared to the Col-0 reference. By biochemically characterizing the phenotypes of 25 of these accessions in greater detail, we discovered that distinct changes in polysaccharide structure resulted in gelatinous coatings with a deceptively similar appearance. Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. In addition, most of the natural variants had altered Pontamine Fast Scarlet 4B staining of cellulose and significantly reduced birefringence of crystalline structures. This indicates that the production or organization of cellulose may be affected by the presence of different amounts of hemicellulose. Although, the accessions described in this study were primarily collected from Western Europe, they form five different phenotypic classes based on the combined results of our experiments. This suggests that polymorphisms at multiple loci are likely responsible for the observed mucilage structure. The transcription of MUCILAGE-RELATED10 (MUCI10), which encodes a key enzyme for galactoglucomannan synthesis, was severely reduced in multiple variants that phenocopied the muci10-1 insertion mutant. Although, we could not pinpoint any causal polymorphisms in this gene, constitutive expression of fluorescently-tagged MUCI10 proteins complemented the mucilage defects of a muci10-like accession. This leads us to hypothesize that some accessions might disrupt a transcriptional regulator of MUCI10. Therefore, this collection of publicly-available variants should provide insight into plant cell wall organization and facilitate the discovery of genes that regulate polysaccharide biosynthesis. PMID- 27375658 TI - Natural Allelic Variations in Highly Polyploidy Saccharum Complex. AB - Sugarcane (Saccharum spp.) is an important sugar and biofuel crop with high polyploid and complex genomes. The Saccharum complex, comprised of Saccharum genus and a few related genera, are important genetic resources for sugarcane breeding. A large amount of natural variation exists within the Saccharum complex. Though understanding their allelic variation has been challenging, it is critical to dissect allelic structure and to identify the alleles controlling important traits in sugarcane. To characterize natural variations in Saccharum complex, a target enrichment sequencing approach was used to assay 12 representative germplasm accessions. In total, 55,946 highly efficient probes were designed based on the sorghum genome and sugarcane unigene set targeting a total of 6 Mb of the sugarcane genome. A pipeline specifically tailored for polyploid sequence variants and genotype calling was established. BWA-mem and sorghum genome approved to be an acceptable aligner and reference for sugarcane target enrichment sequence analysis, respectively. Genetic variations including 1,166,066 non-redundant SNPs, 150,421 InDels, 919 gene copy number variations, and 1,257 gene presence/absence variations were detected. SNPs from three different callers (Samtools, Freebayes, and GATK) were compared and the validation rates were nearly 90%. Based on the SNP loci of each accession and their ploidy levels, 999,258 single dosage SNPs were identified and most loci were estimated as largely homozygotes. An average of 34,397 haplotype blocks for each accession was inferred. The highest divergence time among the Saccharum spp. was estimated as 1.2 million years ago (MYA). Saccharum spp. diverged from Erianthus and Sorghum approximately 5 and 6 MYA, respectively. The target enrichment sequencing approach provided an effective way to discover and catalog natural allelic variation in highly polyploid or heterozygous genomes. PMID- 27375659 TI - Complex Physiological Response of Norway Spruce to Atmospheric Pollution - Decreased Carbon Isotope Discrimination and Unchanged Tree Biomass Increment. AB - Atmospheric pollution critically affects forest ecosystems around the world by directly impacting the assimilation apparatus of trees and indirectly by altering soil conditions, which subsequently also leads to changes in carbon cycling. To evaluate the extent of the physiological effect of moderate level sulfate and reactive nitrogen acidic deposition, we performed a retrospective dendrochronological analysis of several physiological parameters derived from periodic measurements of carbon stable isotope composition ((13)C discrimination, intercellular CO2 concentration and intrinsic water use efficiency) and annual diameter increments (tree biomass increment, its inter-annual variability and correlation with temperature, cloud cover, precipitation and Palmer drought severity index). The analysis was performed in two mountain Norway spruce (Picea abies) stands of the Bohemian Forest (Czech Republic, central Europe), where moderate levels of pollution peaked in the 1970s and 1980s and no evident impact on tree growth or link to mortality has been reported. The significant influence of pollution on trees was expressed most sensitively by a 1.880/00 reduction of carbon isotope discrimination (Delta(13)C). The effects of atmospheric pollution interacted with increasing atmospheric CO2 concentration and temperature. As a result, we observed no change in intercellular CO2 concentrations (Ci), an abrupt increase in water use efficiency (iWUE) and no change in biomass increment, which could also partly result from changes in carbon partitioning (e.g., from below- to above-ground). The biomass increment was significantly related to Delta(13)C on an individual tree level, but the relationship was lost during the pollution period. We suggest that this was caused by a shift from the dominant influence of the photosynthetic rate to stomatal conductance on Delta(13)C during the pollution period. Using biomass increment-climate correlation analyses, we did not identify any clear pollution-related change in water stress or photosynthetic limitation (since biomass increment did not become more sensitive to drought/precipitation or temperature/cloud cover, respectively). Therefore, we conclude that the direct effect of moderate pollution on stomatal conductance was likely the main driver of the observed physiological changes. This mechanism probably caused weakening of the spruce trees and increased sensitivity to other stressors. PMID- 27375661 TI - Drought Stress Predominantly Endures Arabidopsis thaliana to Pseudomonas syringae Infection. AB - Plant responses to a combination of drought and bacterial pathogen infection, an agronomically important and altogether a new stress, are not well-studied. While occurring concurrently, these two stresses can lead to synergistic or antagonistic effects on plants due to stress-interaction. It is reported that plant responses to the stress combinations consist of both strategies, unique to combined stress and those shared between combined and individual stresses. However, the combined stress response mechanisms governing stress interaction and net impact are largely unknown. In order to study these adaptive strategies, an accurate and convenient methodology is lacking even in model plants like Arabidopsis thaliana. The gradual nature of drought stress imposition protocol poses a hindrance in simultaneously applying pathogen infection under laboratory conditions to achieve combined stress. In present study we aimed to establish systematic combined stress protocol and to study physiological responses of the plants to various degrees of combined stress. Here, we have comprehensively studied the impact of combined drought and Pseudomonas syringae pv. tomato DC3000 infection on A. thaliana. Further, by employing different permutations of drought and pathogen stress intensities, an attempt was made to dissect the contribution of each individual stress effects during their concurrence. We hereby present two main aspects of combined stress viz., stress interaction and net impact of the stress on plants. Mainly, this study established a systematic protocol to assess the impact of combined drought and bacterial pathogen stress. It was observed that as a result of net impact, some physiological responses under combined stress are tailored when compared to the plants exposed to individual stresses. We also infer that plant responses under combined stress in this study are predominantly influenced by the drought stress. Our results show that pathogen multiplication was reduced by drought stress in combined stressed plants. Combined stressed plants also displayed reduced ROS generation and declined cell death which could be attributed to activation of effective basal defense responses. We hypothesize a model on ABA mediated gene regulation to partly explain the possible mechanistic basis for reduced in planta bacterial numbers under combined stress over individual pathogen stress. PMID- 27375660 TI - Role of Ubiquitin-Mediated Degradation System in Plant Biology. AB - Ubiquitin-mediated proteasomal degradation is an important mechanism to control protein load in the cells. Ubiquitin binds to a protein on lysine residue and usually promotes its degradation through 26S proteasome system. Abnormal proteins and regulators of many processes, are targeted for degradation by the ubiquitin proteasome system. It allows cells to maintain the response to cellular level signals and altered environmental conditions. The ubiquitin-mediated proteasomal degradation system plays a key role in the plant biology, including abiotic stress, immunity, and hormonal signaling by interfering with key components of these pathways. The involvement of the ubiquitin system in many vital processes led scientists to explore more about the ubiquitin machinery and most importantly its targets. In this review, we have summarized recent discoveries of the plant ubiquitin system and its involvement in critical processes of plant biology. PMID- 27375662 TI - Editorial: Transport in Plant Microbe Interactions. PMID- 27375663 TI - Identification and Validation of Reference Genes for RT-qPCR Analysis in Non Heading Chinese Cabbage Flowers. AB - Non-heading Chinese cabbage (Brassica rapa ssp. chinensis Makino) is an important vegetable member of Brassica rapa crops. It exhibits a typical sporophytic self incompatibility (SI) system and is an ideal model plant to explore the mechanism of SI. Gene expression research are frequently used to unravel the complex genetic mechanism and in such studies appropriate reference selection is vital. Validation of reference genes have neither been conducted in Brassica rapa flowers nor in SI trait. In this study, 13 candidate reference genes were selected and examined systematically in 96 non-heading Chinese cabbage flower samples that represent four strategic groups in compatible and self-incompatible lines of non-heading Chinese cabbage. Two RT-qPCR analysis software, geNorm and NormFinder, were used to evaluate the expression stability of these genes systematically. Results revealed that best-ranked references genes should be selected according to specific sample subsets. DNAJ, UKN1, and PP2A were identified as the most stable reference genes among all samples. Moreover, our research further revealed that the widely used reference genes, CYP and ACP, were the least suitable reference genes in most non-heading Chinese cabbage flower sample sets. To further validate the suitability of the reference genes identified in this study, the expression level of SRK and Exo70A1 genes which play important roles in regulating interaction between pollen and stigma were studied. Our study presented the first systematic study of reference gene(s) selection for SI study and provided guidelines to obtain more accurate RT-qPCR results in non-heading Chinese cabbage. PMID- 27375665 TI - Iron Oxide Nanoparticles as a Potential Iron Fertilizer for Peanut (Arachis hypogaea). AB - Nanomaterials are used in practically every aspect of modern life, including agriculture. The aim of this study was to evaluate the effectiveness of iron oxide nanoparticles (Fe2O3 NPs) as a fertilizer to replace traditional Fe fertilizers, which have various shortcomings. The effects of the Fe2O3 NPs and a chelated-Fe fertilizer (ethylenediaminetetraacetic acid-Fe; EDTA-Fe) fertilizer on the growth and development of peanut (Arachis hypogaea), a crop that is very sensitive to Fe deficiency, were studied in a pot experiment. The results showed that Fe2O3 NPs increased root length, plant height, biomass, and SPAD values of peanut plants. The Fe2O3 NPs promoted the growth of peanut by regulating phytohormone contents and antioxidant enzyme activity. The Fe contents in peanut plants with Fe2O3 NPs and EDTA-Fe treatments were higher than the control group. We used energy dispersive X-ray spectroscopy (EDS) to quantitatively analyze Fe in the soil. Peanut is usually cultivated in sandy soil, which is readily leached of fertilizers. However, the Fe2O3 NPs adsorbed onto sandy soil and improved the availability of Fe to the plants. Together, these results show that Fe2O3 NPs can replace traditional Fe fertilizers in the cultivation of peanut plants. To the best of our knowledge, this is the first research on the Fe2O3 NPs as the iron fertilizer. PMID- 27375666 TI - Crossing Methods and Cultivation Conditions for Rapid Production of Segregating Populations in Three Grain Amaranth Species. AB - Grain amaranths (Amaranthus spp.) have been cultivated for thousands of years in Central and South America. Their grains are of high nutritional value, but the low yield needs to be increased by selection of superior genotypes from genetically diverse breeding populations. Amaranths are adapted to harsh conditions and can be cultivated on marginal lands although little is known about their physiology. The development of controlled growing conditions and efficient crossing methods is important for research on and improvement of this ancient crop. Grain amaranth was domesticated in the Americas and is highly self fertilizing with a large inflorescence consisting of thousands of very small flowers. We evaluated three different crossing methods (open pollination, hot water emasculation and hand emasculation) for their efficiency in amaranth and validated them with genetic markers. We identified cultivation conditions that allow an easy control of flowering time by day length manipulation and achieved flowering times of 4 weeks and generation times of 2 months. All three different crossing methods successfully produced hybrid F1 offspring, but with different success rates. Open pollination had the lowest (10%) and hand emasculation the highest success rate (74%). Hot water emasculation showed an intermediate success rate (26%) with a maximum of 94% success. It is simple to perform and suitable for a more large-scale production of hybrids. We further evaluated 11 single nucleotide polymorphism (SNP) markers and found that they were sufficient to validate all crosses of the genotypes used in this study for intra- and interspecific hybridizations. Despite its very small flowers, crosses in amaranth can be carried out efficiently and evaluated with inexpensive SNP markers. Suitable growth conditions strongly reduce the generation time and allow the control of plant height, flowering time, and seed production. In combination, this enables the rapid production of segregating populations which makes amaranth an attractive model for basic plant research but also facilitates further the improvement of this ancient crop by plant breeding. PMID- 27375664 TI - Protein Phosphatase 2A in the Regulatory Network Underlying Biotic Stress Resistance in Plants. AB - Biotic stress factors pose a major threat to plant health and can significantly deteriorate plant productivity by impairing the physiological functions of the plant. To combat the wide range of pathogens and insect herbivores, plants deploy converging signaling pathways, where counteracting activities of protein kinases and phosphatases form a basic mechanism for determining appropriate defensive measures. Recent studies have identified Protein Phosphatase 2A (PP2A) as a crucial component that controls pathogenesis responses in various plant species. Genetic, proteomic and metabolomic approaches have underscored the versatile nature of PP2A, which contributes to the regulation of receptor signaling, organellar signaling, gene expression, metabolic pathways, and cell death, all of which essentially impact plant immunity. Associated with this, various PP2A subunits mediate post-translational regulation of metabolic enzymes and signaling components. Here we provide an overview of protein kinase/phosphatase functions in plant immunity signaling, and position the multifaceted functions of PP2A in the tightly inter-connected regulatory network that controls the perception, signaling and responding to biotic stress agents in plants. PMID- 27375667 TI - Lack of H(+)-pyrophosphatase Prompts Developmental Damage in Arabidopsis Leaves on Ammonia-Free Culture Medium. AB - The plant vacuolar H(+)-pyrophosphatase (H(+)-PPase) functions as a proton pump coupled with the hydrolysis of pyrophosphate (PPi). Loss-of-function mutants (fugu5s and vhp1) of the H(+)-PPase of Arabidopsis thaliana show clear morphological phenotypes in the cotyledons, caused by inhibition of gluconeogenesis from seed storage lipids due to excessive accumulation of PPi. In this study, we investigated the phenotypes of the fugu5 and vhp1 mutants during vegetative growth under a specific nitrogen nutritional regime. When nitrate in the culture medium was the sole nitrogen source, growth of the mutant rosette leaves was severely compromised. Interestingly, trypan blue staining revealed notable cell death at the leaf blade-petiole junctions of young leaves, a region known to have meristematic features. Physical contact of the leaf tip with the culture medium also triggered leaf atrophy, suggesting that absorption of some elements through the hydathodes was probably involved in this phenotype. Prevention of such leaf-medium contact resulted in a marked decrease in phosphate content in the shoots, and suppressed leaf atrophy. Furthermore, fugu5 necrotic symptoms were rescued completely by heterologous expression of yeast cytosolic soluble pyrophosphatase IPP1 or uncoupling-type H(+)-PPases that retained only PPi-hydrolysis activity, indicating that the damage of actively proliferating cells was caused by the loss of the PPi-hydrolyzing function of H(+)-PPase. Importantly, cell death and growth defects of the fugu5 leaves were suppressed completely by the simple addition of ammonium (>1 mM) to the culture medium. The PPi content in the shoots of fugu5 grown on ammonium-free medium was 70% higher than that of the wild type, and PPi levels were restored to normal upon growth on ammonium-supplemented medium. Together, these findings suggest that the PPi hydrolyzing activity of H(+)-PPase is essential to maintain the PPi contents at optimal levels when grown on ammonium-free culture medium, and any direct contact of the leaves with the culture medium may raise PPi levels in the leaves through increased phosphate uptake. PMID- 27375668 TI - Stover Composition in Maize and Sorghum Reveals Remarkable Genetic Variation and Plasticity for Carbohydrate Accumulation. AB - Carbohydrates stored in vegetative organs, particularly stems, of grasses are a very important source of energy. We examined carbohydrate accumulation in adult sorghum and maize hybrids with distinct phenology and different end uses (grain, silage, sucrose or sweetness in stalk juice, and biomass). Remarkable variation was observed for non-structural carbohydrates and structural polysaccharides during three key developmental stages both between and within hybrids developed for distinct end use in both species. At the onset of the reproductive phase (average 65 days after planting, DAP), a wide range for accumulation of non structural carbohydrates (free glucose and sucrose combined), was observed in internodes of maize (11-24%) and sorghum (7-36%) indicating substantial variation for transient storage of excess photosynthate during periods of low grain or vegetative sink strength. Remobilization of these reserves for supporting grain fill or vegetative growth was evident from lower amounts in maize (8-19%) and sorghum (9-27%) near the end of the reproductive period (average 95 DAP). At physiological maturity of grain hybrids (average 120 DAP), amounts of these carbohydrates were generally unchanged in maize (9-21%) and sorghum (16-27%) suggesting a loss of photosynthetic assimilation due to weakening sink demand. Nonetheless, high amounts of non-structural carbohydrates at maturity even in grain maize and sorghum (15-18%) highlight the potential for developing dual purpose (grain/stover) crops. For both species, the amounts of structural polysaccharides in the cell wall, measured as monomeric components (glucose and pentose), decreased during grain fill but remained unchanged thereafter with maize biomass possessing slightly higher amounts than sorghum. Availability of carbohydrates in maize and sorghum highlights the potential for developing energy rich dedicated biofuel or dual-purpose (grain/stover) crops. PMID- 27375669 TI - Characterization and Expression Analysis of PtAGL24, a SHORT VEGETATIVE PHASE/AGAMOUS-LIKE 24 (SVP/AGL24)-Type MADS-Box Gene from Trifoliate Orange (Poncirus trifoliata L. Raf.). AB - The transition from vegetative to reproductive growth in perennial woody plants does not occur until after several years of repeated seasonal changes and alternative growth. To better understand the molecular basis of flowering regulation in citrus, a MADS-box gene was isolated from trifoliate orange (precocious trifoliate orange, Poncirus trifoliata L. Raf.). Sequence alignment and phylogenetic analysis showed that the MADS-box gene is more closely related to the homologs of the AGAMOUS-LIKE 24 (AGL24) lineage than to any of the other MADS-box lineages known from Arabidopsis; it is named PtAGL24. Expression analysis indicated that PtAGL24 was widely expressed in the most organs of trifoliate orange, with the higher expression in mature flowers discovered by real-time PCR. Ectopic expression of PtAGL24 in wild-type Arabidopsis promoted early flowering and caused morphological changes in class I transgenic Arabidopsis. Yeast two-hybrid assay revealed that PtAGL24 interacted with Arabidopsis AtAGL24 and other partners of AtAGL24, suggesting that the abnormal morphology of PtAGL24 overexpression in transgenic Arabidopsis was likely due to the inappropriate interactions between exogenous and endogenous proteins. Also, PtAGL24 interacted with SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (PtSOC1) and APETALA1 (PtAP1) of citrus. These results suggest that PtAGL24 may play an important role in the process of floral transition but may have diverse functions in citrus development. PMID- 27375670 TI - Blue Light-Induced Intracellular Movement of Phototropins: Functional Relevance or Red Herring? PMID- 27375671 TI - Gene Mapping of a Mutant Mungbean (Vigna radiata L.) Using New Molecular Markers Suggests a Gene Encoding a YUC4-like Protein Regulates the Chasmogamous Flower Trait. AB - Mungbean (Vigna radiata L.) is a cleistogamous plant in which flowers are pollinated before they open, which prevents yield improvements through heterosis. We previously generated a chasmogamous mutant (CM) mungbean in which open flowers are pollinated. In this study, we developed insertion/deletion (indel) markers based on the transcriptome differences between CM and Sulu-1 (i.e., normal flowering) plants. An F2 population derived from a cross between CM and Sulu-1 was used for gene mapping. Segregation analyses revealed that a single recessive gene regulates the production of chasmogamous flowers. Using newly developed indel and simple sequence repeat markers, the cha gene responsible for the chasmogamous flower trait was mapped to a 277.1-kb segment on chromosome 6. Twelve candidate genes were detected in this segment, including Vradi06g12650, which encodes a YUCCA family protein associated with floral development. A single base pair deletion producing a frame-shift mutation and a premature stop codon in Vradi06g12650 was detected only in CM plants. This suggested that Vradi06g12650 is a cha candidate gene. Our results provide important information for the molecular breeding of chasmogamous mungbean lines, which may serve as new genetic resources for hybrid cultivar development. PMID- 27375672 TI - Novel Hydraulic Vulnerability Proxies for a Boreal Conifer Species Reveal That Opportunists May Have Lower Survival Prospects under Extreme Climatic Events. AB - Top dieback in 40-60 years old forest stands of Norway spruce [Picea abies (L.) Karst.] in southern Norway is supposed to be associated with climatic extremes. Our intention was to learn more about the processes related to top dieback and in particular about the plasticity of possible predisposing factors. We aimed at (i) developing proxies for P 50 based on anatomical data assessed by SilviScan technology and (ii) testing these proxies for their plasticity regarding climate, in order to (iii) analyze annual variations of hydraulic proxies of healthy looking trees and trees with top dieback upon their impact on tree survival. At two sites we selected 10 tree pairs, i.e., one healthy looking tree and one tree with visual signs of dieback such as dry tops, needle shortening and needle yellowing (n = 40 trees). Vulnerability to cavitation (P 50) of the main trunk was assessed in a selected sample set (n = 19) and we thereafter applied SilviScan technology to measure cell dimensions (lumen (b) and cell wall thickness (t)) in these specimen and in all 40 trees in tree rings formed between 1990 and 2010. In a first analysis step, we searched for anatomical proxies for P 50. The set of potential proxies included hydraulic lumen diameters and wall reinforcement parameters based on mean, radial, and tangential tracheid diameters. The conduit wall reinforcement based on tangential hydraulic lumen diameters ((t/b ht)(2)) was the best estimate for P 50. It was thus possible to relate climatic extremes to the potential vulnerability of single annual rings. Trees with top dieback had significantly lower (t/b ht)(2) and wider tangential (hydraulic) lumen diameters some years before a period of water deficit (2005 2006). Radial (hydraulic) lumen diameters showed however no significant differences between both tree groups. (t/b ht)(2) was influenced by annual climate variability; strongest correlations were found with precipitation in September of the previous growing season: high precipitation in previous September resulted in more vulnerable annual rings in the next season. The results are discussed with respect to an "opportunistic behavior" and genetic predisposition to drought sensitivity. PMID- 27375673 TI - Biochemical, Transcriptional, and Bioinformatic Analysis of Lipid Droplets from Seeds of Date Palm (Phoenix dactylifera L.) and Their Use as Potent Sequestration Agents against the Toxic Pollutant, 2,3,7,8-Tetrachlorinated Dibenzo-p-Dioxin. AB - Contamination of aquatic environments with dioxins, the most toxic group of persistent organic pollutants (POPs), is a major ecological issue. Dioxins are highly lipophilic and bioaccumulate in fatty tissues of marine organisms used for seafood where they constitute a potential risk for human health. Lipid droplets (LDs) purified from date palm, Phoenix dactylifera, seeds were characterized and their capacity to extract dioxins from aquatic systems was assessed. The bioaffinity of date palm LDs toward 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic congener of dioxins was determined. Fractioned LDs were spheroidal with mean diameters of 2.5 um, enclosing an oil-rich core of 392.5 mg mL(-1). Isolated LDs did not aggregate and/or coalesce unless placed in acidic media and were strongly associated with three major groups of polypeptides of relative mass 32-37, 20-24, and 16-18 kDa. These masses correspond to the LD-associated proteins, oleosins, caleosins, and steroleosins, respectively. Efficient partitioning of TCDD into LDs occurred with a coefficient of log K LB/w,TCDD = 7.528 +/- 0.024; it was optimal at neutral pH and was dependent on the presence of the oil-rich core, but was independent of the presence of LD-associated proteins. Bioinformatic analysis of the date palm genome revealed nine oleosin like, five caleosin-like, and five steroleosin-like sequences, with predicted structures having putative lipid-binding domains that match their LD stabilizing roles and use as bio-based encapsulation systems. Transcriptomic analysis of date palm seedlings exposed to TCDD showed strong up-regulation of several caleosin and steroleosin genes, consistent with increased LD formation. The results suggest that the plant LDs could be used in ecological remediation strategies to remove POPs from aquatic environments. Recent reports suggest that several fungal and algal species also use LDs to sequester both external and internally derived hydrophobic toxins, which indicates that our approach could be used as a broader biomimetic strategy for toxin removal. PMID- 27375674 TI - Corrigendum: Effect of temperature on the pathogenesis, accumulation of viral and satellite RNAs and on plant proteome in peanut stunt virus and satellite RNA infected plants. AB - [This corrects the article on p. 903 in vol. 6, PMID: 26579153.]. PMID- 27375675 TI - Zinc Excess Triggered Polyamines Accumulation in Lettuce Root Metabolome, As Compared to Osmotic Stress under High Salinity. AB - Abiotic stresses such as salinity and metal contaminations are the major environmental stresses that adversely affect crop productivity worldwide. Crop responses and tolerance to abiotic stress are complex processes for which "-omic" approaches such as metabolomics is giving us a newest view of biological systems. The aim of the current research was to assess metabolic changes in lettuce (Lactuca sativa L.), by specifically probing the root metabolome of plants exposed to elevated isomolar concentrations of NaCl and ZnSO4. Most of the metabolites that were differentially accumulated in roots were identified for stress conditions, however the response was more intense in plants exposed to NaCl. Compounds identified in either NaCl or ZnSO4 conditions were: carbohydrates, phenolics, hormones, glucosinolates, and lipids. Our findings suggest that osmotic stress and the consequent redox imbalance play a major role in determining lettuce root metabolic response. In addition, it was identified that polyamines and polyamine conjugates were triggered as a specific response to ZnSO4. These findings help improve understanding of how plants cope with abiotic stresses. This information can be used to assist decision-making in breeding programs for improving crop tolerance to salinity and heavy metal contaminations. PMID- 27375677 TI - Random Projection for Fast and Efficient Multivariate Correlation Analysis of High-Dimensional Data: A New Approach. AB - In recent years, the advent of great technological advances has produced a wealth of very high-dimensional data, and combining high-dimensional information from multiple sources is becoming increasingly important in an extending range of scientific disciplines. Partial Least Squares Correlation (PLSC) is a frequently used method for multivariate multimodal data integration. It is, however, computationally expensive in applications involving large numbers of variables, as required, for example, in genetic neuroimaging. To handle high-dimensional problems, dimension reduction might be implemented as pre-processing step. We propose a new approach that incorporates Random Projection (RP) for dimensionality reduction into PLSC to efficiently solve high-dimensional multimodal problems like genotype-phenotype associations. We name our new method PLSC-RP. Using simulated and experimental data sets containing whole genome SNP measures as genotypes and whole brain neuroimaging measures as phenotypes, we demonstrate that PLSC-RP is drastically faster than traditional PLSC while providing statistically equivalent results. We also provide evidence that dimensionality reduction using RP is data type independent. Therefore, PLSC-RP opens up a wide range of possible applications. It can be used for any integrative analysis that combines information from multiple sources. PMID- 27375676 TI - Reviving the RNA World: An Insight into the Appearance of RNA Methyltransferases. AB - RNA, the earliest genetic and catalytic molecule, has a relatively delicate and labile chemical structure, when compared to DNA. It is prone to be damaged by alkali, heat, nucleases, or stress conditions. One mechanism to protect RNA or DNA from damage is through site-specific methylation. Here, we propose that RNA methylation began prior to DNA methylation in the early forms of life evolving on Earth. In this article, the biochemical properties of some RNA methyltransferases (MTases), such as 2'-O-MTases (Rlml/RlmN), spOUT MTases and the NSun2 MTases are dissected for the insight they provide on the transition from an RNA world to our present RNA/DNA/protein world. PMID- 27375679 TI - Corrigendum: A Quantitative Assessment of Factors Affecting the Technological Development and Adoption of Companion Diagnostics. AB - [This corrects the article on p. 357 in vol. 6, PMID: 26858745.]. PMID- 27375678 TI - Choreographing the Double Strand Break Response: Ubiquitin and SUMO Control of Nuclear Architecture. AB - The cellular response to DNA double strand breaks (DSBs) is a multifaceted signaling program that centers on post-translational modifications including phosphorylation, ubiquitylation and SUMOylation. In this review we discuss how ubiquitin and SUMO orchestrate the recognition of DSBs and explore how this influences chromatin organization. We discuss functional outcomes of this response including transcriptional silencing and how pre-existing chromatin states may control the DSB response and the maintenance of genomic stability. PMID- 27375681 TI - Insulin receptor-like ectodomain genes and splice variants are found in both arthropods and human brain cDNA. AB - Truncated receptor ectodomains have been described for several classes of cell surface receptors, including those that bind to growth factors, cytokines, immunoglobulins, and adhesion molecules. Soluble receptor isoforms are typically generated by proteolytic cleavage of the cell surface receptor or by alternative splicing of RNA transcripts arising from the same gene encoding the full-length receptor. Both the epidermal growth factor receptor (EGFR) and the insulin receptor (INSR) families produce soluble receptor splice variants in vertebrates and truncated forms of insulin receptor-like sequences have previously been described in Drosophila. The EGFR and INSR ectodomains share significant sequence homology with each other suggestive of a common evolutionary origin. We discovered novel truncated insulin receptor-like variants in several arthropod species. We performed a phylogenetic analysis of the conserved extracellular receptor L1 and L2 subdomains in invertebrate species. While the segregation of insulin receptor-like L1 and L2 domains indicated that an internal domain duplication had occurred only once, the generation of truncated insulin receptor like sequences has occurred multiple times. The significance of this work is the previously unknown and widespread occurrence of truncated isoforms in arthropods, signifying that these isoforms play an important functional role, potentially related to such isoforms in mammals. PMID- 27375680 TI - Reflections on the Field of Human Genetics: A Call for Increased Disease Genetics Theory. AB - Development of human genetics theoretical models and the integration of those models with experiment and statistical evaluation are critical for scientific progress. This perspective argues that increased effort in disease genetics theory, complementing experimental, and statistical efforts, will escalate the unraveling of molecular etiologies of complex diseases. In particular, the development of new, realistic disease genetics models will help elucidate complex disease pathogenesis, and the predicted patterns in genetic data made by these models will enable the concurrent, more comprehensive statistical testing of multiple aspects of disease genetics predictions, thereby better identifying disease loci. By theoretical human genetics, I intend to encompass all investigations devoted to modeling the heritable architecture underlying disease traits and studies of the resulting principles and dynamics of such models. Hence, the scope of theoretical disease genetics work includes construction and analysis of models describing how disease-predisposing alleles (1) arise, (2) are transmitted across families and populations, and (3) interact with other risk and protective alleles across both the genome and environmental factors to produce disease states. Theoretical work improves insight into viable genetic models of diseases consistent with empirical results from linkage, transmission, and association studies as well as population genetics. Furthermore, understanding the patterns of genetic data expected under realistic disease models will enable more powerful approaches to discover disease-predisposing alleles and additional heritable factors important in common diseases. In spite of the pivotal role of disease genetics theory, such investigation is not particularly vibrant. PMID- 27375682 TI - Medical errors; causes, consequences, emotional response and resulting behavioral change. AB - OBJECTIVE: To determine the causes of medical errors, the emotional and behavioral response of pediatric medicine residents to their medical errors and to determine their behavior change affecting their future training. METHODS: One hundred thirty postgraduate residents were included in the study. Residents were asked to complete questionnaire about their errors and responses to their errors in three domains: emotional response, learning behavior and disclosure of the error. The names of the participants were kept confidential. Data was analyzed using SPSS version 20. RESULTS: A total of 130 residents were included. Majority 128(98.5%) of these described some form of error. Serious errors that occurred were 24(19%), 63(48%) minor, 24(19%) near misses,2(2%) never encountered an error and 17(12%) did not mention type of error but mentioned causes and consequences. Only 73(57%) residents disclosed medical errors to their senior physician but disclosure to patient's family was negligible 15(11%). Fatigue due to long duty hours 85(65%), inadequate experience 66(52%), inadequate supervision 58(48%) and complex case 58(45%) were common causes of medical errors. Negative emotions were common and were significantly associated with lack of knowledge (p=0.001), missing warning signs (p=<0.001), not seeking advice (p=0.003) and procedural complications (p=0.001). Medical errors had significant impact on resident's behavior; 119(93%) residents became more careful, increased advice seeking from seniors 109(86%) and 109(86%) started paying more attention to details. Intrinsic causes of errors were significantly associated with increased information seeking behavior and vigilance (p=0.003) and (p=0.01) respectively. CONCLUSION: Medical errors committed by residents have inadequate disclosure to senior physicians and result in negative emotions but there was positive change in their behavior, which resulted in improvement in their future training and patient care. PMID- 27375683 TI - The Syrian civil war: The experience of the Surgical Intensive Care Units. AB - OBJECTIVE: Since the civilian war in Syria began, thousands of seriously injured trauma patients from Syria were brought to Turkey for emergency operations and/or postoperative intensive care. The aim of this study was to present the demographics and clinical features of the wounded patients in Syrian civil war admitted to the surgical intensive care units in a tertiary care centre. METHODS: The records of 80 trauma patients admitted to the Anaesthesia, General Surgery and Neurosurgery ICUs between June 1, 2012 and July 15, 2014 were included in the study. The data were reviewed regarding the demographics, time of presentation, place of reference, Acute Physiology and Chronic Health Evaluation II (APACHE II) score and Injury Severity Score (ISS), surgical procedures, complications, length of stay and mortality. RESULTS: A total of 80 wounded patients (70 males and 10 females) with a mean age of 28.7 years were admitted to surgical ICUs. The most frequent cause of injury was gunshot injury. The mean time interval between the occurrence of injury and time of admission was 2.87 days. Mean ISS score on admission was 21, and mean APACHE II score was 15.7. APACHE II scores of non survivors were significantly increased compared with those of survivors (P=0.001). No significant differences was found in the age, ISS, time interval before admission, length of stay in ICU, rate of surgery before or after admission. CONCLUSION: The most important factor affecting mortality in this particular trauma-ICU patient population from Syrian civil war was the physiological condition of patients on admission. Rapid transport and effective initial and on-road resuscitation are critical in decreasing the mortality rate in civil wars and military conflicts. PMID- 27375684 TI - Cardiovascular risk score in Rheumatoid Arthritis. AB - OBJECTIVE: To determine the 10-year Cardiovascular risk score with QRISK-2 and Framingham risk calculators in Rheumatoid Arthritis and Non Rheumatoid Arthritis subjects and asses the usefulness of QRISK-2 and Framingham calculators in both groups. METHODS: During the study 106 RA and 106 Non RA patients age and sex matched participants were enrolled from outpatient department. Demographic data and questions regarding other study parameters were noted. After 14 hours of fasting 5 ml of venous blood was drawn for Cholesterol and HDL levels, laboratory tests were performed on COBAS c III (ROCHE). QRISK-2 and Framingham risk calculators were used to get individual 10-year CVD risk score. RESULTS: In this study the mean age of RA group was (45.1+/-9.5) for Non RA group (43.7+/-8.2), with female gender as common. The mean predicted 10-year score with QRISK-2 calculator in RA group (14.2+/-17.1%) and Non RA group was (13.2+/-19.0%) with (p value 0.122). The 10-year score with Framingham risk score in RA group was (12.9+/-10.4%) and Non RA group was (8.9+/-8.7%) with (p-value 0.001). In RA group QRISK-2 (24.5%) and FRS (31.1%) cases with predicted score were in higher risk category. The maximum agreement scores between both calculators was observed in both groups (Kappa = 0.618 RA Group; Kappa = 0.671 Non RA Group). CONCLUSION: QRISK-2 calculator is more appropriate as it takes RA, ethnicity, CKD, and Atrial fibrillation as factors in risk assessment score. PMID- 27375685 TI - Pulmonary artery closure in combination with patch technique for treating congenital heart disease combined with large patent ductus arteriosus: A clinical study of 9 cases. AB - OBJECTIVE: To document clinical experience of treating congenital heart disease combined with large patent ductus arteriosus with pulmonary artery closure in combination with patch technique. METHODS: Thirty-six patients (8 males and 28 females) who suffered from congenital heart disease and underwent hybrid surgery in the First Affiliated Hospital of Zhengzhou University from October 2010 to February 2014 were selected for this study. They aged 14 to 39 years and weighed 32.20 to 61.50 kg. Diameter of arterial duct was between 10 mm and 13 mm; 28 cases were tube type, 4 cases were funnel type and four cases were window type. All patients had moderate or severe pulmonary arterial hypertension; besides, there were 28 cases of ventricular septal defect, 16 cases of atrial septal defect, eight cases of aortic insufficiency, four cases of mitral stenosis and insufficiency and four cases of infectious endocarditis. Cardz Pulmonary Bypass (CPB) was established after chest was opened along the middle line. With the help of Transesophageal echocardiography, large patent ductus arteriosus was blocked off through pulmonary artery. Pulmonary artery was cut apart after blocking of heart. Large patent ductus arteriosus on the side of pulmonary artery was strengthened with autologous pericardial patch. RESULTS: Of 36 patients, 32 patients had patent ductus arteriosus closure device and four patients had atrial septal defect closure device. Pulmonary arteries of 36 cases were all successfully closed. Systolic pressure declined after closure ((54.86+/-19.23) mmHg vs (96.05+/-23.07) mmHg, p<0.05); average pulmonary arterial pressure also declined after closure ((39.15+/-14.83) mmHg vs (72.88+/-15.76) mmHg, p<0.05). The patients were followed up for one to fifty one months (average 11.5 months). Compared to before surgery, left atrial diameter, left ventricular diameter and pulmonary artery diameter all narrowed after surgery. Besides, clinical symptoms were relieved and cardiac function of the patients also improved. CONCLUSION: Hybrid surgery is feasible and safe in treating patients with large patent ductus arteriosus and congenital heart disease, which decreases surgical problems, shortens surgical time and lowers the incidence of complications. PMID- 27375686 TI - The effect of fibromyalgia syndrome to gravidity, parity and duration of breastfeeding; A prospective study from Turkey. AB - OBJECTIVES: Fibromyalgia syndrome (FS) is a chronic pain disorder usually affecting women in their fertile period of life. However, the relationship between FS and pregnancy has not been studied in depth. The effect of FS on the course of pregnancy is poorly investigated in the current literature. Here we aimed to investigate the effects of FS to menarche age, gravidity, parity and duration of breastfeeding. METHODS: One hundred and eighty-seven non-pregnant females attending between March 2015-June 2015, to Malatya State Hospital Physical Medicine and Rehabilitation Outpatient Clinic, were included in this prospective study. One hundred eleven (111) of them were diagnosed with FS according to the American Rheumatology Association (ACR) 2010 criteria and were defined as group 1; group 2 comprised of seventy six (76) non-pregnant healthy volunteers. All participants were asked about their menarche age, marriage age, gravidity, parity, duration of breastfeeding by conducting a basic questionnaire survey. Patients' body mass index (BMI) were recorded. Depression parameters were evaluated by Beck Depression Scale (BDS). RESULTS: The average age of the patients was 39.04+/-9.21 (FS) and 38.47+/-9.65 (Control) years; first menarche age was at 13.28+/-1.38 (FS) and 13.59+/-1.54 years (Control), and marriage age was 20.1+/-3.62 (FS) and 20.69+/-3.90 years (Control), respectively. No statistically significant difference was found (p=0.598) between BMI values (FS, 27.76+/-4.95; Control 26.90+/-4.56 kg/m(2)). The results from both groups were similar in terms of gravidity, parity, and breastfeeding duration, with no statistically significant differences (p=0.252, 0.093, 0.075, respectively). The only significant difference was found in the depression parameter. The BDS results were statistically different between the groups, found higher in FS group (p=0.000). CONCLUSION: FS occurs as a result of symptoms such as mood disorder, anxiety, cognitive and sleep disorders, and also hormonal changes; no exact cause has yet been established. The syndrome usually occurs during fertile period of young female. According to the findings of our study, FS has no negative effect on the outcome of gravidity, parity, and duration of breastfeeding in Turkish women. Further studies about the effects of FS on the course of pregnancy are required. PMID- 27375687 TI - Influence of silane and heated silane on the bond strength of lithium disilicate ceramics - An in vitro study. AB - OBJECTIVES: To evaluate the effect of silane application and silane heat treatment on lithium-disilicate ceramic when bonded to composite resin. METHODS: Twelve blocks of lithium-disilicate (LD) ceramic were fabricated and bonding surfaces were etched using 9.5% hydrofluoric acid (90 seconds). Three experimental groups resulted from the various surface treatment combinations, which included, no silane application (NS) (controls), silane application (S) and silane heat treatment (HS) (100 degrees C for 5 minutesutes). Ceramic and composite resin blocks were bonded using an adhesive resin and light cured restorative composite as a luting agent, under standard conditions. A total of 90 specimen sticks (8 x 1mm2) were subjected to micro-tensile bond strength testing. The means of micro-tensile bond strength (u-tbs) of the study groups were analyzed using t-test and ANOVA. The tested specimens were analyzed for mode of failure using scanning electron microscopy (SEM). RESULTS: The highest u-tbs value (42.6 +/-3.70 MPa) was achieved for LD ceramics with heat-dried silane. Both silane application and heat treatment of silane resulted in significant (p<0.05) improvements in micro-tensile bond strength of LD ceramics when bonded to resin composite. CONCLUSIONS: The application of silane and its heat treatment showed significant improvement in bond strength of lithium disilicate ceramic when bonded to composite. PMID- 27375688 TI - Comparison between the treatment area of electrode used for radiofrequency ablation of liver cancer focusing on 15G cooled-tip and CWT electrode. AB - OBJECTIVES: To analyze the comparison between the treatment area of 15Gage internally cooled electrodes and 17 Gage Cool Wet-tip(CWT) electrodes. They are manufactured to broaden treatment area of the tumor in the radiofrequency ablation of hepatocellular carcinoma(HCC). METHODS: The study was designed for 62 patients with a mean age of 61, ranging from 44 to 87 years. The sample comprised of patients who used 15 G internally cooled electrodes and 17 G CWT electrodes respectively. Computed tomography (CT) images obtained after the procedure were observed, however, for the ablation lesion, the volume was determined by measuring complete necrotic tissue that did not contrast enhancement in the image. RESULTS: The treatment area of the tumor after radiofrequency ablation was 17.26+/-6.02 in the CWT, which was bigger than 15G. The treatment area ratio of the treatment before or after was significant at 581.85+/-339.56 in the CWT. After radiofrequency ablation, the treatment area got bigger, as 15G electrodes went toward CWT electrodes. Treatment area per electrode was 1.34 times higher in CWT than in 15G while the treatment area ratio of the treatment before or after was 1.001 times higher in the CWT than 15G. CONCLUSIONS: Ablation is more common for the safety margin in stable tumor and CWT type electrodes that can make larger ablation to reduce the number of times ablation is required for residual tumor and it decreases recurrence, ablation time and reoperation. Therefore it is considered t useful to reduce patients' pain. PMID- 27375690 TI - Therapeutic outcomes of canal wall up mastoidectomy in combination with Type I tympanoplasty in otitis media. AB - OBJECTIVE: To evaluate the therapeutic effects in terms of disease clearance and hearing improvement of canal wall up mastoidectomy in combination with Type I tympanoplasty in otitis media. METHODS: A total of 78 patients (81 ears) with otitis media were treated by canal wall up mastoidectomy in combination with Type I tympanoplasty. The postoperative tympanic membrane morphology, average of pure tone hearing thresholds and average air-bone gap were used as the indices for evaluating therapeutic effects. RESULTS: The patients were followed up for two years in average. All the tympanic membranes recovered, with the ear canals being dry. There were five cases (5 ears) of tympanic membrane retraction and one case of otitis media recurrence. Hearing was effectively recovered by 76.54% (62/81) after surgery. CONCLUSION: Combining canal wall up mastoidectomy with Type I tympanoplasty can treat otitis media safely and effectively due to high postoperative dry ear canal rate, satisfactory reconstruction of hearing and maintenance of ear morphology. PMID- 27375689 TI - Effect of angiotensin converting enzyme inhibitor on glomerular hyperfiltration in patients with type 1 diabetes. AB - OBJECTIVE: To assess the effect of angiotensin converting enzyme inhibition on glomerular filtration rate (GFR) in normotensive patient with type 1 diabetes. METHODS: A two year non-placebo control prospective study was conducted after ethical approval at Diabetes Centre of Diabetic Association of Pakistan, a WHO collaborating centre in Karachi, Pakistan. All patients with type 1 diabetes visited the out-patients department from August 2009 till July 2011 and those who fulfilled the inclusion criteria were invited to participate. A total of 121 people aged >=18 years and >= 5 years of diabetes were included. Pregnant and lactating woman and those aged <18 years were excluded. GFR was calculated by using CKD-EPI formula (eGFR) at baseline and after two year. On the basis of estimated GFR, patients at baseline were divided according to KDIGO classification of chronic kidney diseases into, hyperfiltration (eGFR >= 100 ml/min) and normal filtration group (eGFR < 100 ml/min). All subjects in hyperfiltration group received ACE inhibitor (treatment group) while patients with normal filtration did not receive ACE inhibitor (control group). RESULTS: Fifty two patients (43%) were in the treatment and sixty nine (57%) were in the control group. At baseline eGFR, systolic and diastolic blood pressures between groups were non-significantly different. After two years, compared to baseline, eGFR of the treatment group declined and the control group increased significantly. No significant difference in systolic while diastolic blood pressure of the treatment group increased significantly after two years compared to baseline. In contrast both systolic and diastolic blood pressure of control group increased significantly after two years compared to their baseline values. CONCLUSION: Present study demonstrated that initiation of ACEI in hyperfiltration stage declined GFR and keep blood pressure within normal range. PMID- 27375691 TI - Flexible ureteroscopy versus laparoscopy for the treatment of patients who initially presented with obstructive pyelonephritis. AB - OBJECTIVE: To compare the safety and effectiveness of flexible ureteroscopy (F URS) with transperitoneal laparoscopic ureterolithotomy (TPLU) in cases of obstructive pyelonephritis secondary to large proximal ureteral stones. METHODS: A series of 42 patients presenting with obstructive pyelonephritis due to proximal ureteral stones larger than 1.5 cm were included from April 2006 to February 2015 in this comparative study. After drainage of pyonephrosis and resolution of sepsis, 22 patients treated with TPLU (Group I), and 20 patients were treated with F-URS (Group II). Preoperative patient and stone characteristics, procedure-related parameters and clinical outcomes were assessed for each group. RESULTS: It was seen that both methods were effective in the treatment of large proximal ureteral stones. However TPLU provided a higher stone free rate (100% vs 80%. p=0.043) and lower retreatment rate. There was no difference between the groups for the operative time and complication rate. On the other hand, patients treated with F-URS had less postoperative pain (p=0.008), a shorter hospital stay (p<0.001) and a faster return to daily activities (p<0.001). CONCLUSIONS: The results of our study show that both F-URS and TPLU are safe and effective surgical procedures for treatment of large proximal ureteral stones after controlling obstructive pyelonephritis. However, TPLU has a higher stone-free rate with comparable operating time and complication rate as compared to F-URS. On the other hand F-URS has the advantages of less postoperative pain, shorter hospital stay and faster return to daily activities. PMID- 27375692 TI - Importance of immature platelet fraction as predictor of immune thrombocytopenic purpura. AB - BACKGROUND AND OBJECTIVE: Immune thrombocytopenic purpura (ITP) is a clinical syndrome in which a decreased number of circulating platelets (thrombocytopenia) manifests as a bleeding tendency, easy bruising (purpura) or extravasation of blood from capillaries into skin and mucous membranes (petechiae). The diagnosis of ITP can be made clinically on the basis of symptoms, we need to see if ITP can be confirmed in patients by quantification of residual RNA containing immature platelets (megakaryocytic mass) or immature platelets fraction (IPF) using automated hematology analyzers (Sysmex XE-2100). METHODS: In order to check the efficacy of IPF% parameter of Sysmex XE-2100 a total of 231 patients of thrombocytopenia were included in this study. Complete blood count (CBC) was estimated. The data was statistically analyzed by SPSS version 17. RESULTS: About 62 patients were diagnosed as ITP and 169 patients were diagnosed as non ITP on the basis of clinical history. The mean IPF % value of ITP patients was 16.39% and the IPF % value of Non ITP patients was ~7.69% respectively. There was no significant difference in IPF% values with respect to time between sampling and acquisition of complete blood count. The diagnostic sensitivity of IPF% as biomarker for ITP and non-ITP was 85.71% (95%CI: 84.04% to 85.96%) and 41.76% (95% CI: 39.87% to 43.65%). CONCLUSION: The mean IPF % value by Sysmex XE-2100 can be used to predict ITP. PMID- 27375693 TI - N-terminal pro-brain natriuretic peptide measurements in hemodynamically significant patent ductus arteriosus in preterm infants. AB - OBJECTIVES: Evaluate the role of NT-proBNP levels in Preterm neonates suffering from PDA and used as a screening tool for predicting HsPDA and guiding physicians to consider early echocardiographic evaluation. METHODS: This is a monocentric prospective blind study which was conducted at Arar Central Hospital, Ar'ar, Saudi Arabia, during the period between Jan 2014 to June 2014. Thirty-three (33) preterm infants born at less than 31 weeks of gestation or weighing less than 1200 g at birth infants were initially enrolled during a 6-month period. Blood samples were collected along with routine blood tests on days 1, 2, 3, and 7 of life for NT-proBNP analysis. Two echocardiographies were systematically performed on day two of life to ascertain about the status of Ductus Arteriosus. RESULTS: The Plasma NT-proBNP levels were high on day one of life and decline from day three to day seven of life except in those infants with significant hsPDA. Plasma NT-proNBP levels on day 2 of infants in the HsPDA group were significantly higher (<0.001) than those in non-HsPDA group. Echocardiogram parameters indicates the significant difference (p<0.002) in Left Atrial and Aortic ratio (LA/AO), Interventricular septum thickness (P<0.03), Left ventricular posterior wall thickness (p<0.05), diastole PDA gradient (p<0.005) between HsPDA and non-HsPDA. CONCLUSIONS: Plasma NT-proBNP level peaked during the first few days after birth and declined rapidly within a week. Therefore, its level may have a role as a screening tool to predict HsPDA and provide more information regarding its spontaneous closure or otherwise. PMID- 27375694 TI - Olfactory neuroblastoma: A clinicopathological experience of a rare entity from Pakistan. AB - OBJECTIVES: To present the clinicopathological experience of Olfactory Neuroblastoma (ONB) with emphasis on histopathological and immunohistochemical features. METHODS: A descriptive cross-sectional study was done on 36 cases of ONB, selected by non-probability purposive sampling. Theses cases of ONB were retrieved and reviewed from surgical pathology database of Aga Khan University Hospital reported between January 1993 and March 2015. RESULTS: Tumor size and age of presentation was wide in range without any distinct bimodal distribution. Nasal cavity was most common site along with involvement of paranasal sinuses. More than 50% cases had Kadish stage A. Microscopically, most cases were Grade-1 and majority showed partial or complete lobular architecture. Neurofibrillary matrix was observed in 2/3(rd) of cases. Among immunohistochemical markers, Neuron Specific Enolase was most frequently expressed. Unusual positive expression of Cytokeratin AE1/AE3 and Cytokeratin CAM5.2 was also seen focally in few cases. CONCLUSION: The ONB has great variability of histological and clinical presentation, and immunohistochemical markers are useful to differentiate from more common small round blue cell tumours of nasal cavity. PMID- 27375695 TI - Nonunion of subtrochanteric fractures: Comminution or Malreduction. AB - OBJECTIVE: This study aimed to investigate the impact on nonunion of the extent of comminution and postoperative displacement in patients surgically treated for subtrochanteric fractures. METHODS: From 2008 to 2013, 44 patients with subtrochanteric fractures underwent surgery and follow-up. Retrospective data collection showed that it had 32 male and 12 female. Their mean age was 45 years. The case distribution according to Seinsheimer classification was as follows: IIA,8; IIB, 5; IIC, 7; IIIA, 8; IIIB, 3; IV, 9; and V, 4. Cephalomedullary nails were used in 28 cases; ordinary nails, in 9; and plates, in 7. After surgery, the fractures were evaluated for displacement on anteroposterior (AP) and lateral radiography. RESULTS: Of the 44 patients, 37 achieved union from primary surgery at a mean time of 8.4 months. Five cases did not show union within the follow-up period. Two cases of nail breakage were diagnosed as non-union. Among the non union cases, two were Seinsheimer classification IIIA; 3, IV; and 2, V. Displacement was observed on the lateral and A Pradiographs of 4 cases, on only the lateral radiographs of two cases, and in neither radiograph of one case. The risk of non-union was approximately 15.4 and 24.2 times higher when displacement was observed on the AP (95% confidence interval [CI]: 1.33-176.82) and lateral images (95% CI: 1.76-335.67), respectively. CONCLUSION: When displacement occurred after surgical treatment for subtrochanteric fractures, the risk of nonunion increased owing to the difficulty achieving stable fixation. PMID- 27375696 TI - Frequency of minimal hepatic encepalopathy in illeterate patients with compensated cirrhosis. AB - OBJECTIVE: To determine frequency of Minimal Hepatic Encephalopathy in illiterate patients with compensated cirrhosis. METHODS: Illiterate patients with compensated cirrhosis with F4 Score on Shear-wave Elastography were selected for study after informed consent. Sample size was estimated at 106. Selected patients were subjected to two tests for detection of MHE, Number Connection Test A and Block Design Test. Patients taking >= 30 seconds were labelled as Positive for MHE. RESULT: Out of 110 selected patients 10.9% were alcoholics and in 8.2% of patients no hepatic virus infection was detected. HCV was positive in 48.2% patients while HBV was positive in 13.6% of patients. MHE was detected in 72 (65.5%) of patients. Major differences were found in MHE Stage II & III by two tests. Over all BDT detected more cases and gave higher Staging in Stage II & III as compared to NCT-A test. CONCLUSION: Minimal Hepatic Encephalopathy (MHE) could be detected in illiterate patients using NCT-A and BDT Tests. PMID- 27375697 TI - Effects of early enteral nutrition on the gastrointestinal motility and intestinal mucosal barrier of patients with burn-induced invasive fungal infection. AB - OBJECTIVE: To evaluate the effects of early enteral nutrition on the gastrointestinal motility and intestinal mucosal barrier of patients with burn induced invasive fungal infection. METHODS: A total of 120 patients with burn induced invasive fungal infection were randomly divided into an early enteral nutrition (EN) group and a parenteral nutrition (PN) group (n=60). The patients were given nutritional support intervention for 14 days, and the expression levels of serum transferrin, albumin, total protein, endotoxin, D-lactic acid and inflammatory cytokines were detected on the 1st, 7th and 14th days respectively. RESULTS: As the treatment progressed, the levels of serum transferrin, albumin and total protein of the EN group were significantly higher than those of the PN group (P<0.05), while the levels of serum endotoxin and D-lactic acid of the form group were significantly lower (P<0.05). After treatment, the expression levels of IL-6 and TNF-alpha were decreased in the EN group, which were significantly different from those of the PN group (P<0.05). During treatment, the incidence rates of complications such as abdominal distension, diarrhea, sepsis, nausea, vomiting and gastric retention were similar. The mean healing time of wound surface was 9.34+/-0.78 days in the EN group and 12.46+/-2.19 days in the PN group, i.e. such time of the former was significantly shorter than that of the latter (P<0.05). CONCLUSION: Treating patients having burn-induced invasive fungal infection by early enteral nutrition support with arginine can safely alleviate malnutrition and stress reaction, strengthen cellular immune function and promote wound healing, thereby facilitating the recovery of gastrointestinal motility and the function of intestinal mucosal barrier. PMID- 27375698 TI - Medication adherence to oral iron therapy in patients with iron deficiency anemia. AB - OBJECTIVE: This study aimed at investigating the factors affecting medication adherence in patients who use oral iron therapy due to iron deficiency anemia. METHODS: A total of 96 female patients in fertile age with mean age of 30+/-10.1 years (range 18-53) who were admitted to Family Medicine Clinic between 01 January and 31 March 2015 and who had received iron therapy within the recent three years were enrolled in the study. Data were collected through a questionnaire form. RESULTS: Of the patients, 39 (40,6%) were detected not to use the medication regularly or during the recommended period. A statistically significant relationship was found between non-adherence to therapy and gastrointestinal side effects and weight gain (p<0.05). CONCLUSION: Medication adherence is deficient in patients with iron deficiency anemia. The most important reason for this seems gastrointestinal side effects, in addition to weight gain under treatment. PMID- 27375699 TI - Cervical Tuberculous Lymphadenitis: Clinico-demographic Profiles of Patients in a Secondary Level Hospital of Bangladesh. AB - OBJECTIVE: Tuberculosis (TB) is a major public health problem in Bangladesh since long. The present incidence and prevalence rates of all forms of TB are 227 and 404/100,000 population respectively. The aim of this study was to find out the clinical characteristics of involved cervical lymph nodes, demographic characteristics of the patients and response to treatment of Cervical Tuberculous Lymphadenitis (CTL) cases. METHODS: A prospective study was performed in Shaheed Shamsuddin Ahmed Hospital, Sylhet, Bangladesh from June 2012 to June 2014. Total 65 patients having CTL attending outpatient department of the hospital were enrolled. RESULTS: Age of the patients ranged from 5 to 60 years with a mean of 25.6 years. Two third (67.7%) of the patients were female. Male: Female ratio was 1:2.1. More than half of the patients came from rural areas (53.8%) and from low socio-economic conditions (58.5%). Most of the patients presented with unilateral (87.7%), multiple (82.3%), matted (68.6%) lymph nodes, <3cm diameter (54%), commonly in right side (57.9%). Abscess was found in 21.5% cases. Discharging sinus was found in 9.2% cases. Most commonly involved lymph node group was level V (59.4%) followed by level II (42.2%). Systemic features were found in 63.07% patients. Associated lung lesion was found in 3.1% cases. FNAC was found positive for tuberculosis in 83.9% cases. Most of the patients (78.46%) were cured with six months anti-tubercular chemotherapy. CONCLUSIONS: Early diagnosis and treatment is critical in reducing the overall prevalence. It is essential to have awareness regarding common presentations of cervical tuberculous lymphadenitis among the general population as well as healthcare professionals working in the resource poor primary and secondary level hospitals. PMID- 27375700 TI - To compare anti-albumin urea effects of valsartan alone with combination of valsartan and amlodipine in patients of chronic kidney disease. AB - OBJECTIVE: To compare anti-albumin urea effects of Valsartan alone with combination of Valsartan and Amlodipine in patients of chronic kidney disease. METHODS: This randomized clinical trial was conducted at the Department of Medicine, Combined Military Hospital Bahawalpur, from April 2014 to 30 September 2014. 140 patients of chronic kidney disease with baseline blood pressure more than 140/90mm Hg having raised urinary albumin: creatinine ratio (UACR). UACR more than 3.5 mg/mmol was considered abnormal. Group-A was treated with Valsartan 80mg daily and Group-B was treated with valsartan 80 and amlodipine 10mg once a day. We did not change the dose of drugs and check spot UACR at base line and after six months with therapy and compare improvement in UACR between Group-A and B. Data was analyzed by statistical software packages (SPSS 16.0). RESULTS: In both the groups, BP was significantly lower than the respective value. Mean decrease in spot UACR in Group-A was 3.18+/-2.64 mg/mmol and UACR in Group-B mean decrease in UACR was 13.01+/-20.11 mg/mmol. P value was< 0.05. CONCLUSION: The combination therapy of valsartan with amlodipine significantly lowers the albuminuria in chronic Kidney disease and reduce the progression of disease as compared to Valsartan alone therapy. PMID- 27375701 TI - Using a double-channel gastroscope reduces procedural time in performing gastric endoscopic submucosal dissection. AB - OBJECTIVE: Complications are important determining factors for safety of endoscopic submucosal dissection (ESD). ESD of large lesions is associated with increased procedural time. This study investigated whether double-channel gastroscope could be used to reduce procedural time in gastric antrum ESD. METHODS: A retrospective cohort study of 46 patients with one gastric antrum lesion resected by ESD was conducted between January 2013 and December 2015. The diameter of a lesion was from 2cm to 4cm in 46 patients. EUS before ESD was used to evaluate the submucosal vascular structure and the location of lesion in gastric wall. Forty six lesions had ESD with either the ordinary gastroscope (OS group) (n=24) or the double-channel gastroscope (DC group) (n=22). RESULTS: The mean procedural time was significantly lower in the DC group than in the OS group (49.1 minutes vs. 20.5 minutes, p=0.04). There were no significant differences in submucosal injection frequency, specimen size, en bloc resection rate and perforation rate between the two endoscopic groups. There was no recurrence in any case during the follow-up period. CONCLUSIONS: Our data suggest that ESD utilizing double-channel gastroscope may provide a better platform for quicker ESD with equal safety. PMID- 27375702 TI - Prevalence of Type II diabetes in District Dir Lower in Pakistan. AB - OBJECTIVE: To investigate the prevalence of type II diabetes and pre-diabetes and its risk factors in the District Dir Lower Pakistan. METHODS: This study was a population based cross--sectional analysis of 1650 individuals of age 20--80 years, using cluster random sampling technique. After an overnight fast, diabetes and pre-diabetes were analyzed according to the World Health Organization recommendation. RESULTS: The prevalence of diabetes and prediabetes was 11.1% and 16.0%, respectively. Type II diabetes was found 11.0% in female and 11.2% in male subjects. Stepwise multiple logistic regression showed that growing age, positive family history, body mass index (obesity), hypertension, exercise (less physical activates), education, monthly income, are statistically significant risk factors with type II diabetes. CONCLUSION: Our results suggest that type II diabetes has become a main health problem in District Dir Lower and better strategies are required to handle this problem. PMID- 27375703 TI - Comparison of cutaneous nerve injury and vessel disruption complications following saphenous vein stripping using big or small olive heads. AB - OBJECTIVE: To compare the nerve injury and vessel disruption complicaitons in patients undergoing saphenous vein stripping using olive heads of different sizes. METHODS: Big olive heads were used in group A (n=50) and small olive heads were used in group B (n=50) from the ankle to the groin; in group C (n=50), the vein was stripped in two sections; in an upward fashion by stripping the distal portion from the ankle to the level of the knee using small olive heads and by stripping the proximal portion from the knee to the level of the groin using big olive heads. RESULTS: Six months after the operation, nerve injury symptoms were identified in 26%, 4%, 6% of patients in groups A, B, and C respectively. Vessel disruption occurred 2% in group A, 32% in group B, and 4% in group C. Both vessel disruption and nerve injury complications of group C were significantly lower than group A and B (p<0.001). CONCLUSION: Saphenous stripping using big olive heads for the proximal portion from the groin down to the level of the knee and using small olive heads for the distal portion from the knee to the level of the ankle is the alternative method which results in minimal nerve injury and vessel disruption. PMID- 27375704 TI - Iron deficiency anaemia is still a major killer of pregnant women. AB - OBJECTIVE: To observe the effects of iron deficiency anaemia on the health and life of pregnant women. METHODS: This cross sectional study was conducted at the Department of Obstetrics and Gynaecology Unit IV, Liaquat University of Medical and Health Sciences Jamshoro from 1st June 2015 to 30(th) November 2015, for the period of 6 months. During this study period all the pregnant women from 13-40 weeks of pregnancy with iron deficiency anaemia having haemoglobin level less than 9 gram% were included, while the pregnant women with other medical disorders were excluded from the study. The data was collected and analyzed on SPSS version 21. RESULT: Out of the 305 pregnant registered women with iron deficiency anaemia most women were young 170(55.73%) between 20-30 years, belonged to low socioeconomic group 254(83.27%), they were multiparous 104(34.09%), having very low haemoglobin level between 1-3 gram % in 54(17.70%) women and between 4-6gram% in162 (53.11%) women. These women were prone to high complications such as ante partum haemorrhage 49(16.06%), renal failure 48(15.73%), disseminated intravascular coagulation 54(17.70%) and 16(5.24%) women died. CONCLUSION: Iron deficiency anaemia is common in pregnant women with higher rates of complications. PMID- 27375705 TI - Clinical comparison of the efficiency and security of balloon dilators versus fascial dilators in percutaneous nephrolithotripsy (PCNL). AB - OBJECTIVE: To compare the efficiency and security of the balloon dilators versus fascial dilators in percutaneous nephrolithotripsy (PCNL), We compared the difference of intraoperative and postoperative parameters of patients using these two different methods of expansion and having no significant statistic differences in peroperative parameters. METHODS: This is a retrospective analysis of 134 patients undergoing PCNL with upper urinary calculi from January 2012 to January 2014 in Luoyang Central Hospital affiliated to Zhengzhou University. These patients meeting the inclusion criteria were divided into two groups: the group of balloon dilators (group A) and the group of fascial dilators (group B). Two groups were compared for success rate of first expansion, clearance of stone, duration of surgery, intraoperative hemorrhage, blood transfusion rate, postoperative hospitalization and the incidence of complications. RESULT: In Group A, a total of 91 patients (51 men and 40 women, mean age 51.22+/-8.96 years, ranged from 28 to 68 years, the calculi maximum diameter from 0.9 to 4.5cm, 28 cases with a history of gravel, mean Body mass index 24.20+/-2.34, 73 cases with hydronephrosis and 26 cases with underlying diseases such as hypertension, diabetes and the like) undergoing PCNL were retrospectively reviewed. Similarly, In Group B, a total of 43 patients (28 men and 15 women, mean age 49.64+/-10.62 years, ranged from 15 to 70 years, the calculi maximum diameter from 1.1 to 5.2cm, 18 cases with a history of gravel, mean Body mass index 24.40+/-2.70, 38 cases with hydronephrosis and 14 cases with underlying diseases such as hypertension, diabetes and the like) undergoing PCNL were retrospectively reviewed. Our results showed that there was a statistically significant better outcome in Group A than in Group B in terms of success rate of first exploration, duration of operation, intraoperative hemorrhage, postoperative hospitalization and the incidence of complications. Additionally, there was no statistically significant difference with respect to clearance of stone and incidence of blood transfusion in the two groups. CONCLUSION: Balloon dilators had shorter operation time, less bleeding, higher success rate of first expansion, less postoperative complications and shorter postoperative hospitalization than fascial dilators in PCNL. PMID- 27375706 TI - Two years' study of Tetanus cases in a Paediatric Intensive Care Unit. AB - OBJECTIVE: To study the demographic and clinical features, outcome, complications and treatment cost of tetanus patients admitted in Paediatirc Intensive Care Unit (PICU) of Civil Hospital Karachi (CHK). METHODS: It is a descriptive observational study conducted at Civil Hospital Karachi from July 2013 to June 2015. Patients of tetanus admitted in PICU during the study period were enrolled. Data was collected from the file records of patients and included the demographic profile, clinical presentation, grade of severity, length of stay, complications and outcome. It also included the cost of treatment. Descriptive statistics were applied to describe the results. RESULTS: During the study period, 23 cases of tetanus were admitted in P.I.C.U. twelve were male and 11 female. Majority of cases (13) belonged to age group 2-6 years. Seventeen cases were unvaccinated and 6 had received only BCG & OPV. None was appropriately vaccinated for age. There were 9 cases of post injury tetanus, 6 of them were males, 5 cases of otogenic tetanus and 9 cases had no clinically identifiable portal of entry. Eleven cases belonged to grade III severity of Ablett classification and 6 had grade IV severity. Mortality in our case series was 26%. Autonomic instability was seen in 17 patients and all of them needed ionotropic support. The estimated cost of per day treatment of a tetanus patient with mechanical ventilation was approximatly 31, 979/Pak Rs and without mechanical ventilation was 20,000/Pak Rs. CONCLUSION: Tetanus is an entirely preventable disease with a high mortality. Treatment is very costly as compared to vaccination which is free of cost. Complete vaccination and proper wound care is the only option to reduce the ongoing burden of tetanus. PMID- 27375707 TI - The healing effect of bone marrow-derived stem cells in acute radiation syndrome. AB - OBJECTIVES: To determine the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on regeneration of bone marrow and intestinal tissue and survival rate in experimental mice with acute radiation syndrome (ARS). METHODS: Forty mice were randomly divided into two equal groups of A receiving no BMSC transplantation and B receiving BMSCs. BMSCs were isolated from the bone marrow and cultured in DMEM media. Both groups were irradiated with 10 Gy (dose rate 0.28 Gy/ min) (60)CO during 35 minutes with a field size of 35*35 for all the body area. Twenty-four hours after gamma irradiation, 150*10(3) cells of passage 5 in 150 ul medium were injected intravenously into the tail. Animals were euthanized one and two weeks after cell transplantation. They were evaluated histologically for any changes in bone marrow and intestinal tissues. The survival rate in mice were also determined. RESULTS: A significant increase for bone marrow cell count and survival rate were observed in group B in comparison to group A. Histological findings denoted to a healing in sample tissues. CONCLUSION: BMSCs could significantly reduce the side effects of ARS and increase the survival rate and healing in injured tissue. As such their transplantation may open a window in treatment of patients with ARS. PMID- 27375708 TI - Passive removal of silicone oil through 23 gauge transconjunctival sutureless vitrectomy system. AB - OBJECTIVE: To study the outcomes of passive removal of silicone oil by 23 Gauge Transconjunctival Sutureless Vitrectomy System. METHODS: This prospective, consecutive case series study was conducted at Ophthalmology Department Unit I, Dow University of Health Sciences, Civil Hospital Karachi from January 2011 to December 2014. Only psuedophakic eyes with silicone oil temponade were selected. Main outcome measures were intra ocular pressure, time taken for removal of silicone oil, per operative and post operative complications. Pre and post operative IOP was compared by using two-tailed paired t-test and mean values with standard deviation were computed using difference of 95% confidence interval. Chi square test was applied for correlation of different variables. P-value of less than 0.05 was considered statistically significant. RESULTS: Out of 79 patients who underwent passive ROSO, 38 (48.1%) were males. Mean age of patients was 47.5+/-7.1 (sd) years. Mean time taken for passive ROSO was 7.31+/-2.41 (sd) minutes. Pre and post operative intra ocular pressure shows statistically significant (p=0.000) decrease in IOP. Retinal redetachment found in 13 (16.5%) cases during follow up period. CONCLUSION: Passive removal of silicone oil with 23 G suture less vitrectomy system is safe and effective in terms of less per operative and post operative complications. In this simple technique, there is less tissue trauma and little time consumed so it provides more comfort to patients and surgeons as well. PMID- 27375709 TI - Comparison of hemorrhoidectomy by LigaSure with conventional Milligan Morgan's hemorrhoidectomy. AB - OBJECTIVE: To compare the efficacy of haemorrhoidectomy done by using LigaSure with conventional Milligan Morgan haemorrhoidectomy. METHODS: This randomized controlled trial was done at Department of Surgery Dow University Hospital Karachi during January 2013 to September 2015. A total of 55 patients were included in the study. Patients were randomly allocated to group A (Haemorrhoidectomy by Ligasure) and group B (Milligan Morgan Haemorrhoiectomy). Efficacies of both procedures were compared by operative time, Blood loss, wound healing, and pain score on immediate, 1st and 7(th) post operative day. RESULTS: Out of total 55 patients 23 were male and 32 were females. The most common group of age involved was between 40 - 60 years. Third degree Heamorrhoids were present in 37 (67.3%) of patients while remaining 18 (32.7%) had fourth degree Heamorrhoids. Group A included 29 cases while Group B included 26 cases. The mean operating time of Group A was 52.5 with standard deviation of 11.9 while it was 36.6+/- 9.8 in the other group. The mean blood loss in group A was 51.92 with standard deviation of 15.68 while it was 70.34+/-25.59 in group B. Overall pain score was less in those patients who underwent Heamorrhoidectomy by Ligasure method. CONCLUSION: The efficacy of Heamorrhoidectomy by Ligasure is better than the traditional Milligan Morgan Heamorrhoidectomy but we need more clinical trials with large sample size and long term follow ups. PMID- 27375710 TI - Comparison of tumor curettage and resection for treatment of giant cell tumor of the bone around the knee joint. AB - OBJECTIVE: To analyze the efficacies of tumor curettage and resection for treatment of giant cell tumor of the bone (GCTB) around the knee joint (KJ). METHODS: A total of 126 KJ-GCTB cases were treated at our department from August 2011 to February 2015. These cases were divided into two groups (A and B) according to treatment methods. Group A underwent tumor curettage, while group B underwent tumor resection. RESULTS: The relapse rates did not differ significantly between the groups (P>0.05), while the complication rate in group A was significantly lower than that in group B (P<0.05). In addition, the Enneking score for group A was significantly higher than that for group B (P<0.05); in addition, postoperative local recurrence, histopathological grading according to Jaffe, and radiographic imaging-based Campanacci's staging positively correlated (P<0.05). CONCLUSION: Tumor curettage was the preferred surgical approach for patients with KJ-GCTB. PMID- 27375711 TI - Therapeutic approaches and long-term follow-up for prenatal hydronephrosis. AB - OBJECTIVE: This study summarises the outcomes of 149 patients who underwent surgery for antenatally diagnosed unilateral hydronephrosis. METHODS: The medical records of such patients over a 23-year period were reviewed retrospectively. Age at the time of operation, preoperative and postoperative mean pelvic diameter on ultrasound, split renal function, washout patterns on scintigraphy, and early and late complications were recorded. RESULTS: The mean preoperative follow-up period was five months (range: 1-66 months). One patient was operated on after 12 months and two patients after five years of follow-up. Mean preoperative pelvic diameter and renal function were 30.8 mm and 38.6%, respectively; all patients had an obstructive wash-out pattern. In the postoperative period, the corresponding measurements were 11.7 mm and 39.2%, with 111 non-obstructive, 24 partially obstructive, and 14 obstructive wash-out patterns. Three patients with severe caliectasis and low renal function underwent surgery despite mild hydronephrosis. The mean postoperative follow-up period was six (range 4-11) years. Complications developed in 14 (9.3%) patients. CONCLUSION: Patients with antenatal hydronephrosis may need surgery even after a follow-up period of six years. Because of the potential late development of complications, postoperative follow up should be continued for 10 years. PMID- 27375712 TI - Conventional clinical and prognostic variables in 150 oral squamous cell carcinoma cases from the indigenous population of Karachi. AB - OBJECTIVE: To analyze clinical and prognostic variables of Oral Squamous Cell Carcinoma (OSCC) cases from the indigenous population of Karachi and to correlate with the common risk factor of tobacco habit. METHODS: The study was conducted at Ziauddin University, Karachi. One hundred fifty OSCC cases were collected from the Oncology Department of Ziauddin University Hospital, North Nazimabad, Karachi and Otolaryngology ward of Civil Hospital, Karachi, during 2011 and 2015. The reporting included demographic details and variables like intra-oral subsites, clinical stage and histological grade. Recurrence of tumor after initial resection was also documented. RESULTS: The patient's population comprised of 98 males and 52 females. The mean age was 47.1+/- 12.22 (range:20-78 years). Maximum numbers were seen in the 41-50 years age group. Urdu-speaking community was the most affected ethnic group (n=75). Clinico-pathological analysis revealed that majority of cases were moderately differentiated (59%) and were either clinical stage II (35%) or IV (29%) tumors. The most common intra-oral subsite came out to be buccal mucosa of cheeks (56%) followed by lateral borders of tongue (21%), lips (13%), alveolar (6%), palate (2.6%) floor of mouth (1.3%), etc. Recurrence was observed in 08 out of 150 cases. All patients underwent primary resection+/ neck dissection and reconstruction where possible. CONCLUSIONS: Overall experience with oral squamous cell carcinoma shows that it has a high tendency for local invasion as well as dissemination to regional lymph nodes, i.e. cervical lymph nodes, both are associated with a poor prognosis. Preventable risk factor of tobacco chewing has been observed in majority of these cases. PMID- 27375713 TI - Clinical effect of minimally invasive intracranial hematoma in treating hypertensive cerebral hemorrhage. AB - OBJECTIVE: To evaluate the clinical effect of minimally invasive intracranial hematoma in treating hypertensive cerebral hemorrhage. METHODS: One hundred and fifty-six patients with hypertensive cerebral hemorrhage were selected. They were randomly divided into the control group (78 cases) and observation group (78 cases). The control group was treated with conventional craniotomy evacuation of hematoma, while the observation group was treated with minimally invasive intracranial hematoma. Neurological impairment score, treatment efficacy and Barthel index were compared between two groups. Comparison results and clinical data of these patients were retrospectively analyzed. RESULTS: Neurological impairment score in observation group had a significantly obvious decrease compared to control group (p < 0.05). Curative effect of observation group was superior to control group and the difference was significant (p < 0.05). Average operation time in observation group (51.20+/-10.30 minutes) was much shorter than control group (108.60+/-12.80 minutes). Amount of hematoma cleared for the first time in control group (75.40+/-10.20 (%)) was more than observation group (45.10+/-8.70 (%)). Hematoma in observation group (3.90+/-0.80 days) disappeared faster than control group (5.80+/-0.90 days). Differences of the above indexes between two groups were all significant (p < 0.05). Moreover, Barthel index of observation group was much better than control group (p < 0.05). CONCLUSION: Treating hypertensive cerebral hemorrhage with minimally invasive intracranial hematoma is remarkably effective. It should be promoted and practiced extensively. PMID- 27375714 TI - Intravenous ketamine, propofol and propofol-ketamine combination used for pediatric dental sedation: A randomized clinical study. AB - BACKGROUND AND OBJECTIVE: Dental treatments cannot bealways performed under local anesthesia inpediatric non-cooperative patients. For this purpose, differentanesthetic techniques have been applied to increase patient comport to dental treatments. METHODS: Sixty children classified as ASA I-II, between aged 3 to 9, who were scheduled to undergo tooth extraction, were enrolled for this randomized study. Group K received 1 mg/kg ketamine, Group P received 1 mg/kg propofol, and Group KP received 0.5 mg/kg propofol plus 0.5 mg/kg ketamine intravenously for anesthesia induction. RESULTS: Recovery time was significantly lower in Group P than Group KP. No significant differences were found between groups regarding HR, before and after the induction, at tenth minute. Fifth minute's HR was higher in Group K than Group KP. Mean arterial pressure (MAP) values were similar at baseline, before and after the induction, and at tenth minute, whereas significantly lower values were found in Group P and Group KP than in Group K at fifth minute. CONCLUSIONS: Although ketamine, propofol and ketamine-propofol combination are effective for sedation in tooth extraction in pediatric patients, propofol may be an excellent alternative, with the shortest recovery, no nausea and vomiting, and reasonable surgical satisfaction. PMID- 27375715 TI - A prospective observational study assessing the outcome of Sepsis in intensive care unit of a tertiary care hospital, Peshawar. AB - OBJECTIVE: The current study aims to explore the factors associated with outcome among patients with severe sepsis and septic shock admitted to the intensive care unit, Northwest General Hospital and Research Centre, Peshawar, Pakistan. METHODS: A prospective observational study was carried out at intensive care unit of our hospital from February 2014 to October 2015. Data was collected using a structured format and statistical analysis was done using SPSS version 20(r). Regression model was applied to identify the factors contributing to the outcome of severe sepsis and septic shock. P-value less than 0.05 was considered statistically significant. RESULTS: Majority of the patients meeting the criteria of this study were male 147 (54.9%) with a mean age of 54.8. The most common source of sepsis was lung infections (42.2%) followed by urinary tract infections (18.7%), soft tissue infections (6.3%) abdominal infections (6%) and in 6.3% patients the source remained unknown. Further analysis has revealed that increase in number of days of hospitalization was observed to be slightly associated with the outcome of the treatment (1.086 [1.002 - 1.178], 0.046). Moreover, the risk of mortality was the higher among the patients with septic shock 22.161[10.055 - 48.840], and having respiratory, kidney and central nervous system complications. Overall it is seen that septic shock alone was found responsible to cause death among 32.0% of the patients (Model 1: R(2) 0.32, p=0.000), and upon involvement of the organ complications the risk of mortality was observed to 42.0%. CONCLUSION: Chances of recovery were poor among the patients with septic shock. Moreover, those patients having respiratory and urinary tract infection are least likely to survive. PMID- 27375716 TI - Anthropometric measurements may be informative for nursing home-acquired pneumonia. AB - OBJECTIVE: To evaluate the relationship between anthropometric measurements and Nursing Home-Acquired Pneumonia (NHAP) risk. METHODS: Consecutive patients of 65 years or elderly who were living in the Balikli Rum Hospital Nursing Homes were included in this prospective study. At the beginning of this study, the patients' anthropometrics values were measured. The patients were followed for one year, and any incidences of pneumonia attacks were recorded. The relationship between the anthropometric measurements and pneumonia occurrences was analyzed. RESULTS: There were 133 inmates at the initial assessments. Of 108 patients who were eligible for the study, 77 (72.2%) were female and 37 (27.8%) were male. The mean age of the group was 79.8+/-10.5. Patients were assigned to a group according to the presence of pneumonia during the one -year follow-up. There were 74 (55.6%) patients who had suffered from at least one attack of pneumonia during the follow up period. The mean triceps skinfold was significantly thinner in the pneumonia group, and the mean handgrip measurements in both the dominant and non-dominant hands were significantly weaker in the pneumonia group. Furthermore, the frequency of Chronic Obstructive Pulmonary Diseases (COPD) was significantly higher in this group (p < 0.001). CONCLUSIONS: The risk of pneumonia was high in the elderly population who live in nursing homes. Simple anthropometric values may be predictive of the potential for Nursing Home-Acquired Pneumonia. PMID- 27375717 TI - Serum IL-17 & eotaxin levels in asthmatic patients with allergic rhinitis. AB - OBJECTIVE: To investigate the serum levels of Interleukin (IL)-17 and eotaxin levels and the relationship between serum IL-17, eotaxin and pulmonary function in asthmatic patients with allergic rhinitis. METHODS: Serum IL-17 and eotaxin levels in asthmatic patients with allergic rhinitis during attacking and remission and in healthy control subjects were measured using enzyme-linked immunosorbent assay (ELISA) kits. Then we studied the correlation between the serum IL-17, eotaxin levels and pulmonary function in patients. RESULTS: Serum IL 17 and eotaxin levels were significantly elevated in patients during asthma attack and remission compared with healthy control subjects. These levels in patients during asthma attack were much higher than those during remission. Furthermore, serum IL-17 and eotaxin levels were negatively correlated with pulmonary function in asthmatic patients with allergic rhinitis, respectively. CONCLUSION: Our findings suggest that IL-17 and eotaxin are important factors in asthma with allergic rhinitis, and the correlation between serum IL-17, eotaxin and lung function possibly lead to improvements in the diagnosis and treatment of asthma with allergic rhinitis and related diseases. PMID- 27375718 TI - Impact of waste management training intervention on knowledge, attitude and practices of teaching hospital workers in Pakistan. AB - OBJECTIVE: To evaluate the sustainability and effectiveness of training as an intervention to improve the knowledge, attitude and practices of hospital workers on health care waste management. METHOD: We conducted this quasi-experimental study in two tertiary care teaching hospitals in Rawalpindi in October 2013. Training, practical demonstrations and reminders on standard waste management were given to 138 hospital workers in one hospital and compared with 137 workers from the control hospital. We collected data 18 months after intervention through a structured questionnaire to assess the impact of the intervention. We used paired t-test to compare the scores on knowledge, attitude and practices at baseline and first follow up and final impact assessment. Chi square test was used to compare group variables between intervention and control groups. RESULTS: After 18 months since intervention the mean scores on knowledge attitude and practices differed statistically significantly since baseline and intervention group had statistically significantly better knowledge positive attitudes and good health care waste management practices (p < 0.001). Health care and sanitary workers in intervention group scored statistically significantly higher (p < 0.001). CONCLUSION: Trainings of health and sanitary workers on health care waste management guidelines were sustainable among the intervention group after 18 months which shows the positive impact of our intervention. It is recommended that the trainings as intervention be included in the overall policies of the public and private sector hospitals in Pakistan and other similar settings. PMID- 27375719 TI - Comparison between continuing midwifery care and standard maternity care in vaginal birth after cesarean. AB - OBJECTIVE: To determine whether continuing midwifery care has more benefits than standard maternity care in vaginal birth after cesarean (VBAC). METHODS: This study was conducted on women in labour who had history of previous cesarean section and received vaginal birth in obstetrical department of our hospital from May 2013 to November 2014. The included patients were divided randomly into observation group and control group. The women in labour allocated to the observation group received continuing midwifery care, and those to control group received standard maternity care in all the stages of labour. The duration of labor stage together with the rate of fetal distress, neonatal asphyxia, vaginal birth and postpartum bleeding were compared between the two groups. RESULTS: Ninety-six participants were included in the current study, forty-eight in each group. The length of labor was significantly longer (p<0.05), the vaginal birth rate was significantly lower (p<0.05) and the postpartum hemorrhage rate was significantly higher (p<0.05) in the control group than the observation group. In addition, the rate of fetal distress and neonatal asphyxia were higher in the control group, but there was no significant difference between the two groups (p>0.05). CONCLUSION: The continuing midwifery care has more benefits than the standard maternity care in vaginal birth after cesarean (VBAC). PMID- 27375720 TI - Pheniramine Maleate is more effective than Lidocaine on Fentanyl Induced Cough. AB - OBJECTIVE: Fentanyl is frequently used during anesthesia induction. The use of fentanyl can cause cough through different mechanisms. Here, we aimed to investigate effects of pheniramine maleate (PM), an antihistaminic agent, and compare it with lidocaine on fentanyl induced cough. METHODS: This is a randomized double-blind prospective clinical study of ASA I-II, 120 patients scheduled for elective abdominal surgery. Patients were administered drugs intravenously and randomly allocated into three groups: Group C (2 ml 0.9 % normal saline), Group L (1mg/kg lidocaine), and Group F (PM 45.5 mg). 90 seconds after administration, 2u/kg fentanyl was applied in three seconds to all patients. Severity of cough (mild: 1-2, moderate: 3-5, severe> 5), time of the cough and vital parameters were recorded 90 seconds after fentanyl injection. RESULTS: Eight patients (25%) in Group C had fentanyl induced cough whereas three patients (7.5%) in Group L and one patient (2.5%) in Group F experienced this phenomenon. There was statistically significant difference between Group F and Group C (p<0.05); however, differences between Group L and Group C or Group F and Group L were not statistically significant (p>0.05). CONCLUSIONS: Pheniramine Maleate 45.5 mg is better that placebo and as effective as lidocaine to prevent fentanyl induced cough. PMID- 27375721 TI - Students' perception of educational environment at Aga Khan University Medical College, Karachi, Pakistan. AB - OBJECTIVE: To assess educational environment in Aga Khan University Medical College (AKUMC) by Dundee Ready Educational Environmental Measure (DREEM) scale. METHODS: A cross-sectional survey of students at the AKUMC with simple random sampling was carried out from June 2014 till March 2015. Responses in five subscales were used to calculate DREEM scores. RESULTS: The average DREEM score was 125.77+/-16.8 with a reliability of 91.3%. With regards to subscales, on the 12-item students' perceptions of learning (PoL) subscale, the maximum score was 48; 11 items of students' perceptions of teachers (PoT) had a maximum score of 44; students' academic self-perceptions (ASP) identified by 8 items showed maximum score of 32; students' perceptions of atmosphere (PoA) with 12 items obtained maximum score 48 and students' social self-perceptions (SSP) subscale of 7 items had a maximum score of 28. CONCLUSION: Students perceived a positive learning environment at AKUMC Karachi. PMID- 27375722 TI - Apparent Diffusion Coefficient analysis of encephalitis: A comparative study with topographic evaluation and conventional MRI findings. AB - OBJECTIVE: Our purpose was to reveal the efficiency of diffusion weighted imaging (DWI) in the diagnosis of encephalitis, and to determine the relation between the apparent diffusion coefficient (ADC) values, the onset of the clinical symptoms, and the lesion extent. METHODS: Conventional magnetic resonance imaging (MRI) was performed in 17 patients with encephalitis diagnosed on the basis of laboratory, clinical and radiologic findings during 2009 and 2015. Based on the duration between the onset of the symptoms and the brain MRI findings, the patients were divided into three groups. ADC values of the encephalitis lesion, the lesions' topographic analysis score, deep gray matter involvement, patients' clinical situation and the duration of the arrival to the clinic was examined. RESULTS: Mean ADC values were 0,988+/-0,335 x10(-3) mm(2)/s in group I (0-2 days), 1,045+/ 0,347 x10(-3) mm(2)/s in Group-II (3-7 days), 1,451+/-0,225 x10(-3) mm(2)/s in Group-III (8 days and over). The relation between the ADC values and the duration of the arrival, topographic analysis score, the relation between the patients' clinical situation and the deep gray matter involvement were found to be statistically significant. The deep gray matter involvement was demonstrated more clearly by FLAIR images when compared with DWI. CONCLUSION: Conventional MRI sequences may be insufficient in showing the encephalitis lesion. DWI must be added to the imaging modalities immediately in the cases suspected of having encephalitis. PMID- 27375723 TI - Factors affecting the decision to hospitalise children admitted to the emergency department due to non-fatal suicide attempts by pills. AB - OBJECTIVE: Suicide attempts (SAs) in the paediatric age group represent an important cause of morbidity and mortality. Our aim was to examine the factors affecting the decision to hospitalize children with a diagnosis of non-fatal SA by pills. METHODS: Children <18 years of age admitted with SA by pills during 2014 were evaluated retrospectively. Patients were divided into two groups: Group I comprised hospitalised patients and Group-II included those who were discharged from the PED. These two groups were compared in terms of clinical and demographic characteristics recorded upon PED admission. RESULTS: A total of 196 patients were included in the study. The number of pills taken for self-poisoning in Group I (median: 20 pills) was higher than that in Group-II (median: 12 pills) (p < 0.001), and the rate of pathological findings during the first paediatric psychiatric consultation was higher in Group-I (91.1%) than in the Group-II (54.8%) (p < 0.001). CONCLUSION: Factors affecting the disposition decision in cases of children who performed non-fatal SA via pills included the amount of medication taken for the suicide attempt and the presence of psychiatric disorders, as determined by a paediatric psychiatrist during the acute phase. PMID- 27375724 TI - Clinical characteristics of Clostridium difficile-associated diarrhea among patients in a tertiary care center in China. AB - OBJECTIVE: This study investigated the incidence, risk factors, and clinical characteristics of Clostridium difficile-associated diarrhea (CDAD) in Chinese patients. METHODS: Fecal specimens of patients with antibiotic-associated diarrhea (AAD) were collected to test C. difficile toxin A and B using enzyme linked fluorescent assay to identify CDAD. By adopting a nested case-control design, the matched people (ratio 1:3) without AAD were included as controls. RESULTS: Out of 56,172 inpatients, 39,882 (71.0%) used antibiotics, 470 suffered from AAD, and 93 were diagnosed with CDAD. The incidence of nosocomial CDAD was 166 per 100,000. The proportion of CDAD in AAD was 19.8%. CDAD patients presented with more severe clinical manifestations and exhibited more concurrent illness. Logistic regression analysis showed the risk factors of CDAD: advanced age, nasogastric tube-feeding, high APACHE II scores, high level of serum C-reaction protein, low level of serum albumin, severe underlining disease or comorbidity, and number of antibiotic intake. Twenty-nine patients (31.2%) were cured with vancomycin, 54 (58.1%) were cured after dual therapy of vancomycin plus metronidazole, 7 (7.5%) died of underlying diseases aggravated with CDAD, and 3 (3.2%) were transferred to other hospitals for personal reasons. CONCLUSION: The incidence of nosocomial CDAD in China was high. Some risk factors could predispose CDAD. PMID- 27375725 TI - Correlation between ovarian morphology and biochemical and hormonal parameters in polycystic ovary syndrome. AB - OBJECTIVE: To determine the biochemical and hormonal differences in polycystic ovary syndrome (PCOS) patients with and without polycystic ovary (PCO) morphology and to evaluate the outcomes resulting from those differences. METHODS: The study included a total of 83 patients with PCOS; 43 of them had PCO morphology (Group I) and 40 did not (Group-II). Serum LDL, HDL, total cholesterol, triglyceride (TG), total testosterone (T), follicle stimulating hormone (FSH), luteinizing hormone (LH), 17b-estradiol (E2), prolactin (PRL), thyroid stimulating hormone (TSH), sex hormone binding globulin (SHBG), glucose and insulin levels were determined. Homoeostatic model assessment insulin resistance (HOMA-IR) index was calculated. RESULTS: The two groups were similar with respect to BMI. The systolic and diastolic blood pressure measurements of Group-I were significantly lower (p<0.01). Serum mean level of LH (p=0.026) and the mean LH/FSH (p=0.001) level of Group-I were significantly higher than Group-II. The total cholesterol and triglyceride levels of Group-I were significantly lower (p<0.05, p<0.01). The mean HOMA-IR level of Group-I was significantly lower than Group-II (p=0.004). CONCLUSIONS: The group without PCO morphology had a higher risk than the other group in terms of increased insulin resistance, dyslipidemia and cardiovascular diseases due to effects of hyperandrogenism. PMID- 27375726 TI - Fournier's gangrene: Causes, presentation and survival of sixty-five patients. AB - OBJECTIVE: To report our experience with Fournier's Gangrene (FG) over the past eight years and evaluate the predisposing factors which affect the mortality. METHODS: Sixty-five patients who were admitted to emergency surgical unit of our institution presenting with FG between January 2006 and August 2014 were included. The anatomical site of infective gangrene, predisposing factors, etiological factors, and outcomes were retrospectively reviewed. RESULTS: Our cases included 8 women and 57 men. The average age of men was 51+/-13.9 (range 19 75) and the average age of women was 63+/-10.5 (range 52-76). Average hospitalization time was 9.2+/-6.6 days (range 5-25) days. The most frequent comorbid disease was diabetes mellitus and the most frequent etiology was perianal abscess. Colostomy was performed in 11 patients, orchidectomy in two patients, cystostomy in two patients. Notably, all of the 8 (12.3%) patients who died from FG had diabetes and low socioeconomic status. A total of six patients who died required more than one surgical debridement. CONCLUSIONS: Fournier's gangrene is a severe surgical emergency, with a high mortality rate. Low socioeconomic status, diabetes and more than one debridement play a major role in mortality and morbidity. PMID- 27375727 TI - Trends of contraception among ladies of local population in Pakistan; why, how, when and what? AB - OBJECTIVE: To analyze trends of use of methods of contraception along with study of impact of various demographic and social factors on contraception in Peshawar, Pakistan. METHODS: A cross-sectional descriptive study with random purposive sampling was conducted at Combined Military Hospital Peshawar, from Mar 2015-Nov 2015. Self-designed questionnaire with demographic details and questions pertinent to contraceptive practices was utilized as study instrument. Females reporting to concerned hospital for contraceptive advice and prescription were distributed with questionnaire and written informed consent form. Formal approval was taken from ethical committee of hospital. Data was analyzed via descriptive analysis (SPSS-21), qualitative data was expressed as frequencies and percentages; quantitative as mean+/-standard deviation (SD). Main outcome variable i-e contraceptive device used; was cross-tabulated with independent variables. RESULTS: Response rate was 53.2% (n-426). Usage of contraceptive device was as follows; 51.2% Nil, 9.4% barriers, 22.3% oral/injectable hormones, 13.4% IUCDs, 3.8% sterilization. There was a strong relationship between type of contraceptives used and age (p<0.001), client's education (p<0.001), husband's education (p<0.001), number of children (p<0.001), religion (p0.013), socioeconomic class (p<0.001), and religious beliefs about use of contraceptives (p<0.001). More Muslims considered contraception irreligious than non-Muslims (p 0.02). There was no significant impact of husbands' pressure to not to use contraceptives on type of contraception practised (p 0.114). CONCLUSION: Contraceptive devices are under-utilized in the study participants. Multidisciplinary approach should be applied to enhance client education, awareness and counseling to utilize these devices more appropriately and regularly. PMID- 27375728 TI - A Needle-Free Injection System (INJEXTM) with lidocaine for epidural needle insertion: A randomized controlled trial. AB - OBJECTIVES: Local anesthetic infiltration is also a process of a painful process itself. INJEXTM technology, known as "Needle-free" drug delivery system, was designed for reducing the pain associated with cutaneous procedures. We conducted a prospective, randomized trial to evaluate the application of lidocaine with INJEXTM system and 27-gauge needle. METHODS: A total of 60 consecutive patients were allocated to receive either INJEX group or 27-gauge needle group. Local anesthetic infiltration was applied two minutes before epidural needle insertion. RESULTS: Mean VAS, at the time of local anesthetic injection was 0 for group I and 2 for group II. When the effect of epidural needle insertion was compared, the mean VAS score was one versus two for Group-I versus Group-II, respectively. Lidocaine applied with the INJEXTM system before epidural needle insertion significantly reduced the intensity of pain during that procedure and was least effective the lidocaine applied with the 27-gauge needle and patients felt less pain during at the time of local anesthetic injection in Group-I. CONCLUSION: Needle-free delivery of lidocaine is an effective, easy to-use and noninvasive method of providing local anesthesia for the epidural needle insertion. PMID- 27375729 TI - Association of blood neutrophil lymphocyte ratio in the patients with postmenopausal osteoporosis. AB - OBJECTIVE: To investigate the relationship between blood neutrophil lymphocyte ratio (NLR) and postmenopausal osteoporosis in Chinese women without diabetes. METHODS: Two hundred and thirty three postmenopausal women without diabetes were included in this study. The clinical data of patients including age, and body mass index (BMI) were recorded. Blood samples were obtained to determine Blood urea nitrogen (BUN), Uric acid (UA), Albumin (ALB), Creatinine (CREA), Total Cholesterol(TC), Triglyceride (TG), Fasting plasma glucose (FPG), Glycosylated Hemoglobin (HbAlc), 25-hydroxyitamin D (25-OHD) level. NLR was calculated using the following formulas: NLR = Neutrophil count / lymphocyte count; Bone mineral density (BMD) of the lumbar vertebrae and the femoral neck was measured. The relationship between NLR and postmenopausal osteoporosis statistical methods was analyzed. RESULTS: Age, BMD, Albumin (ALB), Creatinine(CREA), Triglyceride (TG) and NLR level were different in the three groups (P<0.05). Logistic regression analysis showed that the age and NLR level were risk factors for postmenopausal osteoporosis. CONCLUSIONS: NLR level was strongly associated with BMD in the postmenopausal women without diabetes, suggesting that NLR could become a helpful clinical tool in the assessment of postmenopausal osteoporosis. PMID- 27375731 TI - Application of career related research in Pakistan: The case of apples vs mangoes. AB - Career choice of medical graduates is dependent on a number of factors as identified in literature across the globe. This article presents an overview of contemporary research on career choices of medical graduates and the generalisation of findings in Pakistan. A number of issues are highlighted which include lack of standardised instruments, classification of specialties and mixed evidence regarding variables and socio cultural differences.. PMID- 27375730 TI - Investigative and extrapolative role of microRNAs' genetic expression in breast carcinoma. AB - MicroRNAs (miRs) are non-coding ribonucleic acids consisting of about 18-22 nucleotide bases. Expression of several miRs can be altered in breast carcinomas in comparison to healthy breast tissue, or between various subtypes of breast cancer. These are regulated as either oncogene or tumor suppressors, this shows that their expression is misrepresented in cancers. Some miRs are specifically associated with breast cancer and are affected by cancer-restricted signaling pathways e.g. downstream of estrogen receptor-alpha or HER2/neu. Connection of multiple miRs with breast cancer, and the fact that most of these post transcript structures may transform complex functional networks of mRNAs, identify them as potential investigative, extrapolative and predictive tumor markers, as well as possible targets for treatment. Investigative tools that are currently available are RNA-based molecular techniques. An additional advantage related to miRs in oncology is that they are remarkably stable and are notably detectable in serum and plasma. Literature search was performed by using database of PubMed, the keywords used were microRNA (52 searches) AND breast cancer (169 searches). PERN was used by database of Bahria University, this included literature and articles from international sources; 2 articles from Pakistan on this topic were consulted (one in international journal and one in a local journal). Of these, 49 articles were shortlisted which discussed relation of microRNA genetic expression in breast cancer. These articles were consulted for this review. PMID- 27375732 TI - Mother's perceptions of child mental health problems and services: A cross sectional study from Lahore. AB - OBJECTIVE: To assess the perceptions of mothers regarding child mental health problems, its causes, preferred treatment options, and to determine whom they would consult, if their child had a psychiatric illness. METHODS: Following informed consent, a questionnaire covering perceptions regarding various aspects of child mental illness was used for data collection from mothers. They were asked to identify the symptoms and behaviours they considered psychopathological in children, which treatments they would prefer, where they would turn for help with a mentally ill child, and their understanding of the causes of child psychiatric disorders in addition to ways to increase awareness of child psychiatric issues in the society. RESULTS: Ninety one mothers participated in the study. They equally perceived emotional, behavioural and cognitive symptoms as suggestive of mental ill health in childhood. Mothers perceived multiple causes of child mental health problems, including family problems, economic difficulties, social adversity and possession by evil spirits. A substantial proportion preferred medication, recitation of Holy Quran and psychotherapy as the preferred treatment options. Overall, mothers preferred consulting health professionals than religious scholars and faith healers. They were keen for steps to increase mental health awareness within their society. CONCLUSION: Despite different cultural perspective, mothers exhibit good understanding of symptoms of child mental health issues and appear open to various services and treatment options. Understanding parental perceptions and expectations from child psychiatric services are crucial in increasing families' engagement in treatment. PMID- 27375733 TI - Gastric perforation without generalized peritonitis; A very rare complication after necrosectomy for necrotizing pancreatitis. AB - Gastric perforation is a very rare complication of necrotizing pancreatitis. We present an interesting case of gastric perforation after necrosectomy for necrotizing pancreatitis without generalized peritonitis. Abdominal drain was seen inside the stomach on endoscopy and there were no clinical features of generalized peritonitis even after 10 days of surgery. Patient was re-explored. The drain was removed and stomach was primarily repaired. The patient recovered uneventfully and was discharged home on 6(th) post operative day. On follow-up visit after one month patient was doing very well and had no complications. PMID- 27375734 TI - Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1 Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin. AB - We are reporting a timely case of atypical euglycemic diabetic ketoacidosis in a type 1 diabetic patient treated with sodium-glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin. The clinical history, physical examination findings and laboratory values are described. Other causes of acidosis such as salicylate toxicity or alcohol intoxication were excluded. Ketoacidosis resolved after increasing dextrose and insulin doses supporting the hypothesis that SGLT-2 inhibitors may lead to hypoinsulinemia. Euglycemic ketoacidosis did not recur in our patient after discontinuing canagliflozin. We recommend reserving SGLT2 inhibitor therapy to type 2 diabetics, discontinuing medication and treating patients presenting with ketoacidosis due to SGLT-2 inhibitors with higher concentrations of dextrose with appropriate doses of insulin to help resolve acidosis. PMID- 27375735 TI - Diagnosis and surgical treatment of isolated rectal endometriosis: long term complication of incomplete treatment for pelvic endometriosis. AB - A 40-year-old woman visited our hospital with cyclic hematochezia for four months. The patient had the history of laparoscopic-assisted vaginal hysterectomy because of severe dysmenorrhea two years ago at another tertiary hospital. According to the medical records, the past surgical treatment was incomplete excision of pelvic endometriotic lesions, especially in rectal serosal lesions. A colonoscopy and abdominopelvic computed tomography showed an isolated tumor mimicking neoplasm, in which a biopsy under colonoscopy was performed and the lesion was endometriosis pathologically. Laparoscopic anterior resection (LAR) was performed. There were no complications during intraoperative and postoperative period and the patient was discharged 7 days after the LAR. It is important for reducing of long-term complication like rectal endometriosis that complete and safe excision of pelvic endometriosis with expert surgical strategy. PMID- 27375736 TI - Falsely increased bispectral index values by convective air warming system during kidney transplantation. AB - Bispectral index (BIS) is a reliable parameter for measuring depth of hypnotic level during anesthesia. Convective air warming system is an effective equipment to maintain normothermia during operation. We report falsely elevated BIS value due to convective air warming system while undergoing kidney transplantation. PMID- 27375737 TI - Retraction Announcement. AB - [This retracts the article on p. 972 in vol. 30, PMID: 25225509.]. PMID- 27375738 TI - Metaheuristic Algorithms for Convolution Neural Network. AB - A typical modern optimization technique is usually either heuristic or metaheuristic. This technique has managed to solve some optimization problems in the research area of science, engineering, and industry. However, implementation strategy of metaheuristic for accuracy improvement on convolution neural networks (CNN), a famous deep learning method, is still rarely investigated. Deep learning relates to a type of machine learning technique, where its aim is to move closer to the goal of artificial intelligence of creating a machine that could successfully perform any intellectual tasks that can be carried out by a human. In this paper, we propose the implementation strategy of three popular metaheuristic approaches, that is, simulated annealing, differential evolution, and harmony search, to optimize CNN. The performances of these metaheuristic methods in optimizing CNN on classifying MNIST and CIFAR dataset were evaluated and compared. Furthermore, the proposed methods are also compared with the original CNN. Although the proposed methods show an increase in the computation time, their accuracy has also been improved (up to 7.14 percent). PMID- 27375739 TI - Bowel Perforation in Premature Infants with Necrotizing Enterocolitis: Risk Factors and Outcomes. AB - We aim to determine risk factors and clinical outcomes for bowel perforation in premature infants with NEC. We analyzed clinical data of 57 cases of premature infants with NEC at our NICU between January 2010 and December 2012. Based on the presence of bowel perforation, we divided these infants into two groups: perforated NEC group (n = 10) and nonperforated NEC group (n = 47). We compared general information, clinical characteristics, and laboratory findings between groups. The perforated NEC group, compared to the nonperforated NEC group, had significantly lesser gestational age, lower birth weight, higher prevalence of apnea, mechanical ventilation, sepsis and shock, lower blood pH, higher levels of blood glucose, abnormal WBC count and thrombocytopenia, and elevated CRP (all P < 0.05). Moreover, the perforated NEC group had significantly longer durations of fasting and TPN usage, higher incidences of EUGR and cholestasis, longer duration of antibiotics, higher frequency of advanced antibiotics use, and poorer prognosis than the nonperforated NEC group (all P < 0.05). Bowel perforation in premature infants with NEC was associated with multiple risk factors. Early identification of some of these risk factors in premature infants with NEC may help implement early intervention to reduce the incidence of bowel perforation and thereby improve the prognosis. PMID- 27375740 TI - Chronic Exposure to Arsenic in Drinking Water Causes Alterations in Locomotor Activity and Decreases Striatal mRNA for the D2 Dopamine Receptor in CD1 Male Mice. AB - Arsenic exposure has been associated with sensory, motor, memory, and learning alterations in humans and alterations in locomotor activity, behavioral tasks, and neurotransmitters systems in rodents. In this study, CD1 mice were exposed to 0.5 or 5.0 mg As/L of drinking water for 6 months. Locomotor activity, aggression, interspecific behavior and physical appearance, monoamines levels, and expression of the messenger for dopamine receptors D1 and D2 were assessed. Arsenic exposure produced hypoactivity at six months and other behaviors such as rearing and on-wall rearing and barbering showed both increases and decreases. No alterations on aggressive behavior or monoamines levels in striatum or frontal cortex were observed. A significant decrease in the expression of mRNA for D2 receptors was found in striatum of mice exposed to 5.0 mg As/L. This study provides evidence for the use of dopamine receptor D2 as potential target of arsenic toxicity in the dopaminergic system. PMID- 27375741 TI - Alteration of Thyroid-Related Hormones within Normal Ranges and Early Functional Outcomes in Patients with Acute Ischemic Stroke. AB - This study evaluated the prognostic value of thyroid-related hormones within normal ranges after acute ischemic stroke. This was a retrospective study and we reviewed 1072 ischemic stroke patients consecutively admitted within 72 h after symptom onset. Total triiodothyronine (T3), total thyroxine (T4), free T3, free T4, and thyroid-stimulating hormone (TSH) were assessed to determine their values for predicting functional outcome at the first follow-up clinic visits, which usually occurred 2 to 4 weeks after discharge from the hospital. 722 patients were finally included. On univariate analysis, poor functional outcome was associated with presence of atrial fibrillation as the index event. Furthermore, score of National Institutes of Health Stroke Scale (NIHSS), total T4, free T4, and C-reactive protein at admission were significantly higher in patients with poor functional outcome, whereas free T3 and total T3 were significantly lower. On multiple logistic regression analysis, lower total T3 concentrations remained independently associated with poor functional outcome [odds ratio (OR), 0.10; 95% confidence interval (CI), 0.01-0.84; P = 0.035]. The only other variables independently associated with poor functional outcome were NIHSS scores. In sum, lower total T3 concentrations that were within the normal ranges were independently associated with poor short-term outcomes. PMID- 27375743 TI - Simultaneous Clear Cell Sarcomas of the Duodenum and Jejunum. AB - Clear cell sarcoma (CCS) is an uncommon tumor that usually presents as an extremity mass but can rarely manifest as a gastrointestinal tumor with a diverse spectrum of symptoms, most commonly related to a mass effect or ulceration. Herein we report a case in which two separate tumors, one in the duodenum and the other in the jejunum, present concurrently. The subject presented with symptomatic anemia and underwent imaging and endoscopic studies that culminated in the discovery of the two lesions. He subsequently underwent operative treatment with resection of both tumors and made an unremarkable recovery. The resection specimen consisted of two separate clear cell sarcomas with negative margins. Under microscopic evaluation, they demonstrated nested growths of epithelioid cells with scattered spindled cells infiltrating the enteric wall. The neoplastic cells were positive for S100 with scattered expression of Melan A. Florescence in situ hybridization revealed a translocation at the EWRS1 locus. He was disease-free for 30 months following the procedure; then he developed a rapidly progressing metastatic disease with subsequent death 4 months later. PMID- 27375742 TI - Selective Sensing of Tyrosine Phosphorylation in Peptides Using Terbium(III) Complexes. AB - Phosphorylation of tyrosine residues in proteins, as well as their dephosphorylation, is closely related to various diseases. However, this phosphorylation is usually accompanied by more abundant phosphorylation of serine and threonine residues in the proteins and covers only 0.05% of the total phosphorylation. Accordingly, highly selective detection of phosphorylated tyrosine in proteins is an urgent subject. In this review, recent developments in this field are described. Monomeric and binuclear Tb(III) complexes, which emit notable luminescence only in the presence of phosphotyrosine (pTyr), have been developed. There, the benzene ring of pTyr functions as an antenna and transfers its photoexcitation energy to the Tb(III) ion as the emission center. Even in the coexistence of phosphoserine (pSer) and phosphothreonine (pThr), pTyr can be efficintly detected with high selectivity. Simply by adding these Tb(III) complexes to the solutions, phosphorylation of tyrosine in peptides by protein tyrosine kinases and dephosphorylation by protein tyrosine phosphatases can be successfully visualized in a real-time fashion. Furthermore, the activities of various inhibitors on these enzymes are quantitatively evaluated, indicating a strong potential of the method for efficient screening of eminent inhibitors from a number of candidates. PMID- 27375744 TI - Epidermal Cells Expressing Putative Cell Markers in Nonglabrous Skin Existing in Direct Proximity with the Distal End of the Arrector Pili Muscle. AB - Inconsistent with the view that epidermal stem cells reside randomly spread along the basal layer of the epidermal rete ridges, we found that epidermal cells expressing stem cell markers in nonglabrous skin exist in direct connection with the distal end of the arrector pili muscle. The epidermal cells that express stem cell markers consist of a subpopulation of basal keratinocytes located in a niche at the lowermost portion of the rete ridges at the distal arrector pili muscle attachment site. Keratinocytes in the epidermal stem cell niche express K15, MCSP, and alpha6 integrin. alpha5 integrin marks the distal end of the APM colocalized with basal keratinocytes expressing stem cell markers located in a well-protected and nourished environment at the lowermost point of the epidermis; these cells are hypothesized to participate directly in epidermal renewal and homeostasis and also indirectly in wound healing through communication with the hair follicle bulge epithelial stem cell population through the APM. Our findings, plus a reevaluation of the literature, support the hierarchical model of interfollicular epidermal stem cell units of Fitzpatrick. This new view provides insights into epidermal control and the possible involvement of epidermal stem cells in nonmelanoma skin carcinogenesis. PMID- 27375746 TI - Labeling Adipose-Derived Stem Cells with Hoechst 33342: Usability and Effects on Differentiation Potential and DNA Damage. AB - Adipose-derived stem cells (ASCs) have been extensively studied in the field of stem cell research and possess numerous clinical applications. Cell labeling is an essential component of various experimental protocols and Hoechst 33342 (H33342) represents a cost-effective and easy methodology for live staining. The purpose of this study was to evaluate the labeling of rat ASCs with two different concentrations of H33342 (0.5 MUg/mL and 5 MUg/mL), with particular regard to usability, interference with cell properties, and potential DNA damage. Hoechst 33342 used at a low concentration of 0.5 MUg/mL did not significantly affect cell proliferation, viability, or differentiation potential of the ASCs, nor did it cause any significant DNA damage as measured by the olive tail moment. High concentrations of 5 MUg/mL H33342, however, impaired the proliferation and viability of the ASCs, and considerable DNA damage was observed. Undesirable colabeling of unlabeled cocultivated cells was seen in particular with higher concentrations of H33342, independent of varying washing procedures. Hence, H33342 labeling with lower concentrations represents a usable method, which does not affect the tested cell properties. However, the colabeling of adjacent cells is a drawback of the technique. PMID- 27375745 TI - Utility of Lymphoblastoid Cell Lines for Induced Pluripotent Stem Cell Generation. AB - A large number of EBV immortalized LCLs have been generated and maintained in genetic/epidemiological studies as a perpetual source of DNA and as a surrogate in vitro cell model. Recent successes in reprograming LCLs into iPSCs have paved the way for generating more relevant in vitro disease models using this existing bioresource. However, the overall reprogramming efficiency and success rate remain poor and very little is known about the mechanistic changes that take place at the transcriptome and cellular functional level during LCL-to-iPSC reprogramming. Here, we report a new optimized LCL-to-iPSC reprogramming protocol using episomal plasmids encoding pluripotency transcription factors and mouse p53DD (p53 carboxy-terminal dominant-negative fragment) and commercially available reprogramming media. We achieved a consistently high reprogramming efficiency and 100% success rate using this optimized protocol. Further, we investigated the transcriptional changes in mRNA and miRNA levels, using FC-abs >= 2.0 and FDR <= 0.05 cutoffs; 5,228 mRNAs and 77 miRNAs were differentially expressed during LCL-to-iPSC reprogramming. The functional enrichment analysis of the upregulated genes and activation of human pluripotency pathways in the reprogrammed iPSCs showed that the generated iPSCs possess transcriptional and functional profiles very similar to those of human ESCs. PMID- 27375747 TI - Impact on the Quality of Life When Living Close to a Municipal Wastewater Treatment Plant. AB - The objective of the study was to investigate the impact on the quality of life of people living close to a municipal wastewater treatment plant. A case control study, including 235 inhabitants living within a 500 m radius by a municipal wastewater treatment plant (cases) and 97 inhabitants living in a different area (controls), was conducted. A standardized questionnaire was self-completed by the participants which examined the general health perception and the overall life satisfaction. Also, the concentration of airborne pathogenic microorganisms in aerosol samples collected around the wastewater treatment plant was investigated. Significant risk for symptoms such as headache, unusual tiredness, and concentration difficulties was recorded and an increased possibility for respiratory and skin diseases was reported. A high rate of the cases being irritable and moody was noticed. Significantly higher gastrointestinal symptoms were also reported among the cases in relation to the controls. The prevalence of pathogenic airborne microorganisms originating from the wastewater treatment plant was reported in high numbers in sampling points close to the wastewater treatment plant. More analytical epidemiological investigations are needed to determine the cause as well as the burden of the diseases to inhabitants living surrounding the wastewater treatment plant. PMID- 27375748 TI - Subboiling Moist Heat Favors the Selection of Enteric Pathogen Clostridium difficile PCR Ribotype 078 Spores in Food. AB - Emerging enteric pathogens could have not only more antibiotic resistance or virulence traits; they could also have increased resistance to heat. We quantified the effects of minimum recommended cooking and higher temperatures, individually on a collection of C. difficile isolates and on the survival probability of a mixture of emerging C. difficile strains. While minimum recommended cooking time/temperature combinations (63-71 degrees C) allowed concurrently tested strains to survive, higher subboiling temperatures reproducibly favored the selection of newly emerging C. difficile PCR ribotype 078. Survival ratios for "ribotypes 078" : "other ribotypes" (n = 49 : 45 isolates) from the mid-2000s increased from 1 : 1 and 0.7 : 1 at 85 degrees C (for 5 and 10 minutes, resp.) to 2.3 : 1 and 3 : 1 with heating at 96 degrees C (for 5 and 10 minutes, resp.) indicating an interaction effect between the heating temperature and survival of C. difficile genotypes. In multistrain heating experiments, with PCR ribotypes 027 and 078 from 2004 and reference type strain ATCC 9689 banked in the 1970s, multinomial logistic regression (P < 0.01) revealed PCR ribotype 078 was the most resistant to increasing lethal heat treatments. Thermal processes (during cooking or disinfection) may contribute to the selection of emergent specific virulent strains of C. difficile. Despite growing understanding of the role of cooking on human evolution, little is known about the role of cooking temperatures on the selection and evolution of enteric pathogens, especially spore-forming bacteria. PMID- 27375749 TI - The Validation of a Novel Surveillance System for Monitoring Bloodstream Infections in the Calgary Zone. AB - Background. Electronic surveillance systems (ESSs) that utilize existing information in databases are more efficient than conventional infection surveillance methods. The objective was to assess an ESS for bloodstream infections (BSIs) in the Calgary Zone for its agreement with traditional medical record review. Methods. The ESS was developed by linking related data from regional laboratory and hospital administrative databases and using set definitions for excluding contaminants and duplicate isolates. Infections were classified as hospital-acquired (HA), healthcare-associated community-onset (HCA), or community-acquired (CA). A random sample of patients from the ESS was then compared with independent medical record review. Results. Among the 308 patients selected for comparative review, the ESS identified 318 episodes of BSI of which 130 (40.9%) were CA, 98 (30.8%) were HCA, and 90 (28.3%) were HA. Medical record review identified 313 episodes of which 136 (43.4%) were CA, 97 (30.9%) were HCA, and 80 (25.6%) were HA. Episodes of BSI were concordant in 304 (97%) cases. Overall, there was 85.5% agreement between ESS and medical record review for the classification of where BSIs were acquired (kappa = 0.78, 95% Confidence Interval: 0.75-0.80). Conclusion. This novel ESS identified and classified BSIs with a high degree of accuracy. This system requires additional linkages with other related databases. PMID- 27375751 TI - Diagnosis and Management of Multiple Sclerosis in Children. AB - Growing evidence indicates the safety and well toleration of treatment by Disease modifying in children suffering multiple sclerosis (MS). The treatment is not straight forward in a great number of patients, thus patients with pediatric MS must be managed by experienced specialized centers. Common treatments of multiple sclerosis for adults are first-line therapies. These therapies (firstline) are safe for children. Failure in treatment that leads to therapy alteration is almost prevalent in pediatric MS. Toleration against current second-line therapies has been shown in multiple sclerosis children. Oral agents have not been assessed in children MS patients. Although clinical trials in children are insufficient, immunomodulating managed children, experience a side effect similar to the adult MS patients. However, further prospective clinical studies, with large sample size and long follow-up are needed to distinguish the benefits and probable side effects of pediatric MS therapies. PMID- 27375752 TI - Neurological Manifestations of Renal Diseases in Children in Qazvin/ Iran. AB - OBJECTIVE: Renal diseases are one of the most common causes of referrals and admissions of children, hence it is important to know their neurological presentations. This study aimed to determine neurological presentations of renal diseases in children. MATERIAL & METHODS: A total of 634 children with renal diseases, admitted to Qazvin Pediatric Hospital, Qazvin, central Iran from 2011 to 2013 were studied. Neurological presentations of patients were established and the results were analyzed using statistical tests. RESULTS: Neurological presentations were found in 18 (2.8%) out of 634 patients, of whom 15 had febrile seizures, two thromboembolism, and one encephalopathy. Among patients with urinary tract infection (UTI), 2.6% had febrile seizures, 11.1% of those with glomerulonephritis had encephalopathy, and 3.7% of those with nephrotic syndrome had cerebral thromboembolism. CONCLUSION: Results showed neurological presentations in 2.8% of children with renal diseases, and febrile seizure as the most common presentation. PMID- 27375750 TI - Nutritional Aspects of Treatment in Epileptic Patients. AB - Epilepsy is a neurological disorder characterized by interruption of normal neuronal functions that is manifested by behavioral disorders, changing of awareness level, and presence of some sensory, autonomic and motor symptoms or signs. It is resulted from many different causes. Many antiepileptic drugs (AEDs) are considered to manage epileptic attacks. Some of them change metabolism and absorption of many nutrients. Therefore, epileptic patients may be in higher risk of nutrient deficiency and its unwelcome effects. In the present paper, we intend to review the relationship between nutrition and epilepsy in two aspects. In one aspect we discuss the nutritional status in epileptic patients, the causes of nutritional deficiencies and the way of compensation of the nutrient deficiencies. It will guide these patients to have a healthy life. In another aspect we explain the role of some nutrients and specific diets in management of epileptic attacks. It can help to better control of epileptic attacks in these patients. PMID- 27375753 TI - Effects of Abnormal Oral Reflexes on Speech Articulation in Persian Speaking Children with Spastic Cerebral Palsy. AB - OBJECTIVE: The purpose of this study was to investigate the relationship between the presence of abnormal oral reflexes and speech sound production in children with severe cerebral palsy. MATERIALS & METHODS: Seven oral reflexes such as, rooting, mouth-opening, biting, chewing, lip, tongue, and suckling were examined in 52Persian-speaking monolingual children with spastic cerebral palsy (ages 5-10 yr).Phonetic information tests were administered to investigate their ability for articulation of the speech sounds. RESULTS: A significant relationship between three (i.e. the chewing, lip, and biting reflexes) out of the seven abnormal oral reflexes and the speech articulation was noticed. The presence of the chewing reflex was associated with deficits in production of /s, z, s,c/ sounds. The lip reflex was associated with deficits in the production of /p, m, r, j, f, c/ sounds. The biting reflex was associated with deficits in the production of /z, l, y and s/ sounds. No significant relationship was found between the rooting, mouth-opening, tongue, and suckling reflexes and sound articulation. CONCLUSION: The presence of abnormal reflexes in the children with spastic cerebral palsy would suggest a correlation between these reflexes and sound articulation in Iranian children with spastic cerebral palsy. Hence, these observations might suggest some disturbances in normal speech development. PMID- 27375754 TI - Comparing Mental Health of School-Age Children with and without Epilepsy. AB - OBJECTIVE: Mental health problems frequently occur in children with epilepsy but the diagnosis is frequently missed and therapeutic opportunities are often lost. The aim of this study was to compare mental health statues between school-aged children with epilepsy and the healthy group. MATERIALS & METHODS: In this case, control study, 120 children aged 6 to 12 years with idiopathic epilepsy and 240 healthy control groups were followed up. Children with epilepsy were enrolled from Iranian Epilepsy Association in 2014. The parent version of Child Symptom Inventory-4 questionnaire was used. Mean comparisons were performed using Student's t test while effect sizes were estimated by Cohen's d coefficient. The Chi-Square test was used to assess the difference between frequency distribution of demographic variables in both groups. The significance level was considered less than 0.05. RESULTS: There were statistically significant differences between children with epilepsy and control group as for attention deficit hyperactivity disorder, generalized anxiety disorder, major depression, separation anxiety, social phobia, motor and vocal tics and oppositional defiant disorder. CONCLUSION: The carefully evaluating and prospectively following the psychopathology symptom of children with epilepsy are critical for early identification, prevention and treatment. PMID- 27375755 TI - Phantom Limb Sensation (PLS) and Phantom Limb Pain (PLP) among Young Landmine Amputees. AB - OBJECTIVE: To determine the frequency of phantom limb sensation (PLS) and phantom limb pain (PLP) in children and young adults suffering landmine-related amputation. MATERIALS & METHODS: All youths with amputation due to landmine explosions participated in this study. The proportions of patients with phantom limb sensation/pain, intensity and frequency of pain were reported. Chi square test was used to examine the relationship between variables. Comparison of PLP and PLS between upper and lower amputation was done by unpaired t-test. RESULTS: There were 38 male and 3 female with the mean age of 15.8+/-2.4yr. The mean interval between injury and follow-up was 90.7+/-39.6 months. Twelve (44.4%) upper limb amputees and 11 (26.8%) lower limb amputees had PLS. Nine (33.3%) upper limb amputees and 7 (17.1%) lower limb amputees experienced PLP. Of 27 upper limb amputees, 6 (14.6%) and among 15 lower limb amputees, 6 (14.6%) had both PLS and PLP. One case suffered amputation of upper and lower limbs and was experiencing PLS and PLP in both parts. PLS had a significant difference between the upper and lower amputated groups. Significant relationship was observed between age of casualty and duration of injury with PLP. CONCLUSION: Phantom limb sensation and pain in young survivors of landmine explosions appear to be common, even years after amputation. PMID- 27375756 TI - Predictors of Poor Seizure Control in Children Managed at a Tertiary Care Hospital of Eastern Nepal. AB - OBJECTIVE: Various factors have been claimed to predict outcome of afebrile seizures in children. This study was aimed to find out the predictors of poor seizure control in children at a resource limited setting. MATERIALS & METHODS: This prospective study was done from July 1st, 2009 to January 31st, 2012 at B.P. Koirala Institute of Health Sciences, Nepal. Children (1 month-20 yr of age) with afebrile seizures presenting to pediatric neurology clinic were studied. Significant predictors on bivariate analysis were further analyzed with binary logistic model to find out the true predictors. Positive predictive values (PPVs) and negative predictive values (NPVs) for the true predictors were calculated. RESULTS: Out of 256 patients (male: female ratio 3:2) with afebrile seizures followed up for median duration of 27 (IQR 12-50) months, seizure was poorly controlled in 20% patients. Three factors predicted poor seizure control. They were frequent (>=1 per month) seizures at onset (OR 12.76, 95% CI 1.44-112.73, PPV 25%, NPV 98%); remote symptomatic etiology (OR 3.56, 95% CI 1.04-12.17, PPV 36%, NPV 92%); and need of more than one anticonvulsant drug (polytherapy) (OR 12.83, 95% CI 5.50-29.9, PPV 56%, NPV 96%). The strongest predictor was need of polytherapy. When all three factors were present, PPV and NPV for prediction of poor seizure control were 70% and 90% respectively. CONCLUSION: Frequent seizures at onset, remote symptomatic etiology of seizure and need of polytherapy were associated with poor seizure control in children with afebrile seizures. PMID- 27375757 TI - SerumTrace Elements in Febrile Seizure: A Case-Control Study. AB - OBJECTIVE: Febrile seizure (FS) is one of the most common neurological problems during childhood.Pathogenesis of febrile convulsion is unknown. This study investigated some trace elements among children admitted with FS compared with thoseof febrile without seizure attacks. MATERIALS & METHODS: This case-control study was conducted on48 children (6 months to 5 yrold) diagnosed with febrile seizure as the cases and 48 age-matched febrile children as the control group. Serum levels of magnesium, calcium, sodium, potassium, and serum zinc were measured. Statistical analysis was performed with SPSS (version 15) using Student t-test. RESULTS: There were no significant differences between the cases and controls in terms of gender or age. The means of serum level of zinc, sodium, calcium and magnesium in the case group was lower than those of the control group. There was no significant difference onserum potassium mean level between the case and control groups. CONCLUSION: Deficiency of trace elements was correlated significantly with febrile convulsion, while further investigations on trace elements are required. PMID- 27375758 TI - Relationship of Mothers' Psychological Status with Development of Kindergarten Children. AB - OBJECTIVE: Given the importance of children's development and the role of psychological status of mothers in this regard, this study investigated the relationship of mothers' psychological status (stress, anxiety and depression) with the development of children aged 36-60 months. MATERIALS & METHODS: This descriptive study was performed on 1036 mothers and their children, aged 36 to 60 months, in different kindergartens in Tehran City, Iran, in 2014-2015. Participants were selected through multi-stage random sampling. The following instruments were used in this study: A demographic and obstetric specification questionnaire, children specification questionnaire, the Beck Depression Inventory, Spiel Berger Test, Perceived stress questionnaire and the Ages and Stages Questionnaire to determine the status of the children's development. Data were analyzed using SPSS20 software, Mann-Whitney; independent t-test and logistic-Regression model were used. RESULTS: The prevalence of developmental delay in children aged 36-60 months was 16.2%. The independent t-test showed a relationship between maternal stress and developmental delay in children. The Mann-Whitney test revealed a significant relation between mothers' depression level and developmental delay in their children. There was a significant relation between trait anxiety and developmental delay in children. Moreover, a significant relation was found between maternal stress and developmental delay in fine motor skills. The logistic regression model showed a significant relationship of child gender, economic and social states with developmental delay. CONCLUSION: This study showed mothers' psychological status probably is an effective factor in developmental delay. The assessment of mothers' psychological status is suggested for early interventions. PMID- 27375759 TI - Neurometabolic Diagnosis in Children who referred as Neurodevelopmental Delay (A Practical Criteria, in Iranian Pediatric Patients). AB - OBJECTIVE: We aimed to investigate the clinical and para clinical manifestations of neuro metabolic disorders, in patients who presented by neuro developmental delay in their neuro developmental milestones. MATERIALS & METHODS: The patients diagnosed as neuro developmental delay and regression with or without seizure at the Neurology Department of Mofid Children Hospital in Tehran, Iran between 2004 and 2014 were included in our study. These patients diagnosed as neuro developmental delay by pediatric neurologists in view of diagnostic /screening neuro developmental assessment tests. The patients who completed our inclusion criteria as neuro metabolic disorders were evaluated in terms of metabolic and genetic study in referral lab. RESULTS: Overall, 213 patients with neurometabolic disorders were diagnosed. 54.3% of patients were male. The average age of patients was 41 +-46.1 months. 71.4% of parent's patients had consanguinity of marriages. Eighty seven percent of patients had developmental delay (or/and) regression. 55.5% of them had different type of seizures. Overall, 213 patients with 34 different neurometabolic disorders were diagnosed and classified in the 7 sub classes, consisting of: 1- organic acidemia and aminoacidopathy (122 patients), 2-storage disease (37 patients) 3- eukodystrophy (27 patients), other classes consisted: lipid oxidation disorders, urea cycle disorders, progressive myoclonic epilepsy; and peroxizomal disorders (27 patients). CONCLUSION: In patients with developmental delay or regression, with or without seizure, abnormal neurologic exam along with positive family history of similar disorder or relative parents, abnormal brain imaging with specific patterns, neurometabolic disorders should be considered as one of the important treatable diseases. PMID- 27375760 TI - Cerebellar Infarction in Childhood: Delayed-Onset Complication of Mild Head Trauma. AB - Objective Cerebellar ischemic infarction is a rare complication of minor head trauma. Vertebral artery dissection, vasospasm or systemic hypo perfusion can cause infarct. However, underlying causes of the ischemic infarct cannot be explained in nearly half of cases. The accurate diagnosis is essential to ensure appropriate treatment. Here we report a five yr old boy patient of cerebellar infraction after minor head trauma, admitted to emergency serves of BulentEcevit University, Turkey in 2013. We aimed to remind minor head trauma that causes cerebellar infarction during childhood, and to review the important points of the diagnosis, which should be keep in mind. PMID- 27375761 TI - Hemispherectomy Procedure in Proteus Syndrome. AB - Objective Proteus syndrome is a rare overgrowth disorder including bone, soft tissue, and skin. Central nervous system manifestations were reported in about 40% of the patients including hemimegalencephaly and the resultant hemicranial hyperplasia, convulsions and mental deficiency. We report a 1-month-old male baby referred to Pediatric Neurology Clinic Soetomo Hospital, Surabaya, Indonesia in 2014 presented recurrent seizures since birth with asymmetric dysmorphic face with the right side larger than the left, subcutaneous mass and linear nevi. Craniocervical MRI revealed hemimegalencephaly right cerebral hemisphere. Triple antiepileptic drugs were already given as well as the ketogenic diet, but the seizures persisted. The seizure then was resolved after hemispherectomy procedure. PMID- 27375762 TI - Additive Effect of Qidan Dihuang Grain, a Traditional Chinese Medicine, and Angiotensin Receptor Blockers on Albuminuria Levels in Patients with Diabetic Nephropathy: A Randomized, Parallel-Controlled Trial. AB - Albuminuria is characteristic of early-stage diabetic nephropathy (DN). The conventional treatments with angiotensin receptor blockers (ARB) are unable to prevent the development of albuminuria in normotensive individuals with type 2 diabetes mellitus (T2DM). Purpose. The present study aimed to evaluate the effect of ARB combined with a Chinese formula Qidan Dihuang grain (QDDHG) in improving albuminuria and Traditional Chinese Medicine Symptom (TCMS) scores in normotensive individuals with T2DM. Methods. Eligible patients were randomized to the treatment group and the control group. Results. Compared with baseline (week 0), both treatment and control groups markedly improved the 24-hour albuminuria, total proteinuria (TPU), and urinary albumin to creatinine ratio (A/C) at 4, 8, and 12 weeks. Between treatment and the control group, the levels of albuminuria in the treatment group were significantly lower than in the control group at 8 and 12 weeks (p < 0.05). In addition, treatment group markedly decreased the scores of TCMS after treatment. Conclusion. This trial suggests that QDDHG combined with ARB administration decreases the levels of albuminuria and the scores for TCMS in normotensive individuals with T2DM. PMID- 27375764 TI - Changes in Blood Components in Aphtha Patients with Excess Heat. AB - "Superior heat" is a popularization expression in TCM heat syndrome and has no counterpart in the modern medical system concept. Oral ulcer is considered to be a kind of clinical manifestation of "superior heat." Aphtha is a common and frequently occurring disease, which can be divided into excess heat and Yin deficiency. The aphtha of excess heat manifests the syndromes of acute occurrence, severe local symptoms, obvious swelling and pain, red tongue, yellow coating, and fast-powerful pulse. In this study, we found that there was an abnormal immune regulation in aphtha patients induced by excess heat. There are changes in the blood components, including abnormal serum protein expression (IL 4, MMP-19, MMP-9, and Activin A) and a higher percentage of CD4(+)CD25(+)Treg cells in the peripheral blood lymphocytes of the EXP group. Changes in the blood environment may be an important factor in the occurrence of aphtha caused by excess heat. PMID- 27375763 TI - Supercritical Fluid Extract of Spent Coffee Grounds Attenuates Melanogenesis through Downregulation of the PKA, PI3K/Akt, and MAPK Signaling Pathways. AB - The mode of action of spent coffee grounds supercritical fluid CO2 extract (SFE) in melanogenesis has never been reported. In the study, the spent coffee grounds were extracted by the supercritical fluid CO2 extraction method; the chemical constituents of the SFE were investigated by gas chromatography-mass spectrometry (GC-MS). The effects of the SFE and its major fatty acid components on melanogenesis were evaluated by mushroom tyrosinase activity assay and determination of intracellular tyrosinase activity and melanin content. The expression level of melanogenesis-related proteins was analyzed by western blotting assay. The results revealed that the SFE of spent coffee grounds (1-10 mg/mL) and its major fatty acids such as linoleic acid and oleic acid (6.25-50 MUM) effectively suppressed melanogenesis in the B16F10 murine melanoma cells. Furthermore, the SFE decreased the expression of melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2). The SFE also decreased the protein expression levels of p-JNK, p-p38, p-ERK, and p-CREB. Our results revealed that the SFE of spent coffee grounds attenuated melanogenesis in B16F10 cells by downregulation of protein kinase A (PKA), phosphatidylinositol-3 kinase (PI3K/Akt), and mitogen-activated protein kinases (MAPK) signaling pathways, which may be due to linoleic acid and oleic acid. PMID- 27375765 TI - The Effect of Photoluminescence of Bioceramic Irradiation on Middle Cerebral Arterial Occlusion in Rats. AB - The purpose of this study is to determine the possible effect of photoluminescence of bioceramic (PLB) on ischemic cerebral infarction (stroke), by using an animal model of transient middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were used to induce MCAO to block the origin of the left MCAO; three months later, the positive chronic stroke rats were selected by running tunnel maze; the MCAO rats with significant chronic stroke and neurological defects were used for treadmill experiments with varying speed settings to test their capability for restoration after muscular fatigue under conditions of with and without PLB irradiation. As a result, PLB irradiation could improve exercise completion rate and average running speed during slow and fast treadmill settings. After PLB irradiation, the selected MCAO rats successfully completed all the second-round treadmill exercises at the maximum speed setting, and they had better restoration from muscular fatigue. An in vitro cell study on astrocytes of rats by bioceramic irradiation further demonstrated increased intracellular nitric oxide. To explain these results, we suggest that cortical brain stimulation of microcirculation and enhancement of peripheral muscular activity are the main causes of the improved exercise performance in MCAO rats by PLB. PMID- 27375766 TI - Effect of Kangfuxin Solution on Chemo/Radiotherapy-Induced Mucositis in Nasopharyngeal Carcinoma Patients: A Multicenter, Prospective Randomized Phase III Clinical Study. AB - Objective. To evaluate the efficacy and safety of Kangfuxin Solution, a pure Chinese herbal medicine, on mucositis induced by chemoradiotherapy in nasopharyngeal carcinoma patients. Methods. A randomized, parallel-group, multicenter clinical study was performed. A total of 240 patients were randomized to receive either Kangfuxin Solution (test group) or compound borax gargle (control group) during chemoradiotherapy. Oral mucositis, upper gastrointestinal mucositis, and oral pain were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and the Verbal Rating Scale (VRS). Results. Of 240 patients enrolled, 215 were eligible for efficacy analysis. Compared with the control group, the incidence and severity of oral mucositis in the test group were significantly reduced (P = 0.01). The time to different grade of oral mucositis occurrence (grade 1, 2, or 3) was longer in test group (P < 0.01), and the accumulated radiation dose was also higher in test group comparing to the control group (P < 0.05). The test group showed lower incidence of oral pain and gastrointestinal mucositis than the control group (P < 0.01). No significant adverse events were observed. Conclusion. Kangfuxin Solution demonstrated its superiority to compound borax gargle on mucositis induced by chemoradiotherapy. Its safety is acceptable for clinical application. PMID- 27375767 TI - Elastic band resistance training influences transforming growth factor-beta receptor I mRNA expression in peripheral mononuclear cells of institutionalised older adults: the Vienna Active Ageing Study (VAAS). AB - BACKGROUND: Ageing, inactivity and obesity are associated with chronic low-grade inflammation contributing to a variety of lifestyle-related diseases. Transforming growth factor-beta (TGF-beta) is a multimodal protein with various cellular functions ranging from tissue remodelling to the regulation of inflammation and immune functions. While it is generally accepted that aerobic exercise exerts beneficial effects on several aspects of immune functions, even in older adults, the effect of resistance training remains unclear. The aim of this study was to investigate whether progressive resistance training (6 months) with or without nutritional supplementation (protein and vitamins) would influence circulating C-reactive protein and TGF-beta levels as well as TGF-beta signalling in peripheral mononuclear cells (PBMCs) of institutionalised adults with a median age of 84.5 (65.0-97.4) years. RESULTS: Elastic band resistance training significantly improved performance as shown by the arm-lifting test (p = 0.007), chair stand test (p = 0.001) and 6-min walking test (p = 0.026). These results were paralleled by a reduction in TGF-beta receptor I (TGF-betaRI) mRNA expression in PBMCs (p = 0.006), while circulating inflammatory markers were unaffected. Protein and vitamin supplementation did not provoke any additional effects. Interestingly, muscular endurance of upper and lower body and aerobic performance at baseline were negatively associated with changes in circulating TGF-beta at the early phase of the study. Furthermore, drop-outs of the study were characterised not only by lower physical performance but also higher TGF beta and TGF-betaRI mRNA expression, and lower miRNA-21 expression. CONCLUSIONS: Progressive resistance training with elastic bands did not influence chronic low grade inflammation but potentially affected TGF-beta signalling in PBMCs through altered TGF-betaRI mRNA expression. There appears to be an association between physical performance and TGF-beta expression in PBMCs of older adults, in which the exact mechanisms need to be clarified. PMID- 27375768 TI - Toll-like receptor 9 partially regulates lung inflammation induced following exposure to chicken barn air. AB - BACKGROUND: Exposure to animal barn air is an occupational hazard that causes lung dysfunction in barn workers. Respiratory symptoms experienced by workers are typically associated with endotoxin and TLR4 signalling, but within these environments gram negative bacteria constitute only a portion of the total microbial population. In contrast, unmethylated DNA can be found in all bacteria, some viruses, and mold. We hypothesized that in such environments TLR9, which binds unmethylated DNA, contributes to the overall immune responses in the lung. METHODS: Using a mouse model, wild-type and TLR9(-/-) mice were exposed to chicken barn air for 1, 5, or 20 days. Blood serum and bronchiolar lavage fluid was tested against a panel of six TLR9-induced cytokines (IL-1beta, IL-6, IL-10, IL-12, TNFalpha, and IFNgamma) for changes in expression. Bronchiolar lavage fluid (BAL) was also tested for macrophage as well as monocyte migration. RESULTS: There were significant decreases in serum TNFalpha after a single day exposure in TLR9(-/-) mice. BAL concentrations of TNFalpha and IFNgamma, as well as TNFalpha in serum in TLR9(-/-) mice were also reduced after barn exposure for 5 days. After 20 days of exposure IFNgamma was significantly reduced in lavage of TLR9(-/-) mice. Myeloperoxidase (MPO) accumulation in the lung was reduced at 20 days of exposure in TLR9(-/-) mice, as was total lavage cell counts. However, Masson's staining revealed no apparent lung histological differences between any of the treatment groups. CONCLUSIONS: Taken together our data show TLR9 plays a partial role in lung inflammation induced following exposure to chicken barn air potentially through binding of unmethylated DNA. PMID- 27375769 TI - Antioxidant and physiological effects of Si-Wu-Tang on skin and liver: a randomized, double-blind, placebo-controlled clinical trial. AB - BACKGROUND: Si-Wu-Tang (SWT) is used to treat various gynecological disorders in Chinese medicine. This study investigated the antioxidant and physiological effects of SWT on the skin and liver in healthy adults. METHODS: This randomized, crossover, double-blind, placebo-controlled clinical trial was conducted at Chung Shan Medical University Hospital in December 2008. Participants with uncontrolled diabetes, heart disease, liver disease, kidney disease, cancer, and pregnancy were excluded. Sixty healthy volunteers taking no medications were recruited from the community based on the results of their medical history questionnaires and biochemical analyses to confirm their health status. The participants were assigned to two groups: one group drank 125 mL of placebo (n = 30) and the other drank SWT (n = 30) for six continuous days per month for 6 months. The placebo and SWT were then switched between the groups after a 1-month washout period. Anthropometric measurements (body weight, body fat, and body mass index) were performed and fasting blood samples were drawn for various biochemical assays at 1, 3, 6, 10 and 13 months. Abdominal ultrasound and skin examinations were performed at 1, 6 and 13 months. The skin examinations involved assessment of skin roughness, sebum content, hydration, surface water loss, erythema, melanin index, and elasticity on the face (sunlight-exposed sites: middle of ear and nose) and inner arm (sunlight-unexposed sites: center of wrist and elbow joint). RESULTS: Administration of SWT significantly increased the antioxidant index (P = 0.001) and antioxidant enzymes activities (P = 0.001) from baseline to month 6. SWT also suppressed the concentration of serum lipids (triglycerides, P = 0.01; high-density lipoprotein cholesterol, P = 0.23; low-density lipoprotein cholesterol, P = 0.48) and hepatic marker enzymes (glutamic pyruvic transaminase, P = 0.76; glutamic oxaloacetic transaminase, P = 0.65) when compared with the placebo group. Abdominal ultrasound in the SWT group revealed a positive impact of SWT on mild fatty liver, gallstones, and mild splenomegaly. Moreover, SWT intake concomitantly elevated erythema (P = 0.011) and markedly lowered skin surface water loss (P = 0.016), sebum content (P = 0.021), and wrinkles (P = 0.024). CONCLUSIONS: Oral administration of SWT for 6 months improved the antioxidant level and positively regulated the lipid profile, liver function, and skin integrity and texture. PMID- 27375771 TI - Estimating carbon sequestration in the piedmont ecoregion of the United States from 1971 to 2010. AB - BACKGROUND: Human activities have diverse and profound impacts on ecosystem carbon cycles. The Piedmont ecoregion in the eastern United States has undergone significant land use and land cover change in the past few decades. The purpose of this study was to use newly available land use and land cover change data to quantify carbon changes within the ecoregion. Land use and land cover change data (60-m spatial resolution) derived from sequential remotely sensed Landsat imagery were used to generate 960-m resolution land cover change maps for the Piedmont ecoregion. These maps were used in the Integrated Biosphere Simulator (IBIS) to simulate ecosystem carbon stock and flux changes from 1971 to 2010. RESULTS: Results show that land use change, especially urbanization and forest harvest had significant impacts on carbon sources and sinks. From 1971 to 2010, forest ecosystems sequestered 0.25 Mg C ha-1 yr-1, while agricultural ecosystems sequestered 0.03 Mg C ha-1 yr-1. The total ecosystem C stock increased from 2271 Tg C in 1971 to 2402 Tg C in 2010, with an annual average increase of 3.3 Tg C yr 1. CONCLUSIONS: Terrestrial lands in the Piedmont ecoregion were estimated to be weak net carbon sink during the study period. The major factors contributing to the carbon sink were forest growth and afforestation; the major factors contributing to terrestrial emissions were human induced land cover change, especially urbanization and forest harvest. An additional amount of carbon continues to be stored in harvested wood products. If this pool were included the carbon sink would be stronger. PMID- 27375770 TI - Aikeqing decreases viral loads in SHIV89.6-infected Chinese rhesus macaques. AB - BACKGROUND: Aikeqing (AKQ) has been shown in clinical studies to improve quality of life of HIV/AIDS patients, but anti-HIV activity has not been determined. The SHIV-infected macaque is an important animal model for testing antiviral drugs. This study aimed to determine the anti-HIV activity of AKQ in chronically SHIV89.6-infected Chinese rhesus macaques. METHODS: Nine Chinese rhesus macaques were inoculated intravenously with SHIV89.6 virus. At 11 weeks post-infection, the animals were arbitrarily divided into three groups: high-dose (AKQ 1.65 g/kg; n = 3), low-dose (AKQ 0.55 g/kg; n = 3), and control (water 1 mL/kg; n = 3). Treatment was administered by the intragastric gavage route once-daily for 8 weeks. Blood (5 mL) was collected biweekly. Viral loads were analyzed by real time quantitative RT-PCR assays, and T cell counts were monitored by FACS analyses throughout the treatment. RESULTS: AKQ induced a persistent decline (P = 0.02) in plasma viral loads during treatment in the high-dose group compared with their baseline levels, and cessation of the therapy caused viral load rebound to the pretreatment levels. No significant difference (P = 0.06) was found in the plasma viral loads during treatment in the low-dose group. The CD4(+) T cell counts and CD4/CD8 ratios remained at stable high levels during the treatment period. CONCLUSION: AKQ reduced plasma viral loads in the SHIV89.6-infected Chinese rhesus macaque model. PMID- 27375772 TI - A new tool for prioritization of sequence variants from whole exome sequencing data. AB - BACKGROUND: Whole exome sequencing (WES) has provided a means for researchers to gain access to a highly enriched subset of the human genome in which to search for variants that are likely to be pathogenic and possibly provide important insights into disease mechanisms. In developing countries, bioinformatics capacity and expertise is severely limited and wet bench scientists are required to take on the challenging task of understanding and implementing the barrage of bioinformatics tools that are available to them. RESULTS: We designed a novel method for the filtration of WES data called TAPERTM (Tool for Automated selection and Prioritization for Efficient Retrieval of sequence variants). CONCLUSIONS: TAPERTM implements a set of logical steps by which to prioritize candidate variants that could be associated with disease and this is aimed for implementation in biomedical laboratories with limited bioinformatics capacity. TAPERTM is free, can be setup on a Windows operating system (from Windows 7 and above) and does not require any programming knowledge. In summary, we have developed a freely available tool that simplifies variant prioritization from WES data in order to facilitate discovery of disease-causing genes. PMID- 27375773 TI - Urban Poverty and Neighborhood Effects on Crime: Incorporating Spatial and Network Perspectives. AB - Research on neighborhoods and crime is on a remarkable growth trajectory. In this article, we survey important recent developments in the scholarship on neighborhood effects and the spatial stratification of poverty and urban crime. We advance the case that, in understanding the impact of neighborhoods and poverty on crime, sociological and criminological research would benefit from expanding the analytical focus from residential neighborhoods to the network of neighborhoods individuals are exposed to during their daily routine activities. This perspective is supported by reemerging scholarship on activity spaces and macro-level research on inter-neighborhood connections. We highlight work indicating that non-residential contexts add variation in criminogenic exposure, which in turn influence offending behavior and victimization risk. Also, we draw on recent insights from research on gang violence, social and institutional connections, and spatial mismatch, and call for advancements in the scholarship on urban poverty that investigates the salience of inter-neighborhood connections in evaluating the spatial stratification of criminogenic risk for individuals and communities. PMID- 27375774 TI - Changes in parenting strategies after a young person's self-harm: a qualitative study. AB - BACKGROUND: When faced with the discovery of their child's self-harm, mothers and fathers may re-evaluate their parenting strategies. This can include changes to the amount of support they provide their child and changes to the degree to which they control and monitor their child. METHODS: We conducted an in-depth qualitative study with 37 parents of young people who had self-harmed in which we explored how and why their parenting changed after the discovery of self-harm. RESULTS: Early on, parents often found themselves "walking on eggshells" so as not to upset their child, but later they felt more able to take some control. Parents' reactions to the self-harm often depended on how they conceptualised it: as part of adolescence, as a mental health issue or as "naughty behaviour". Parenting of other children in the family could also be affected, with parents worrying about less of their time being available for siblings. Many parents developed specific strategies they felt helped them to be more effective parents, such as learning to avoid blaming themselves or their child for the self-harm and developing new ways to communicate with their child. Parents were generally eager to pass their knowledge on to other people in the same situation. CONCLUSIONS: Parents reported changes in their parenting behaviours after the discovery of a child's self-harm. Professionals involved in the care of young people who self harm might use this information in supporting and advising parents. PMID- 27375775 TI - Enhanced malic acid production from glycerol with high-cell density Ustilago trichophora TZ1 cultivations. AB - BACKGROUND: In order to establish a cost-efficient biodiesel biorefinery, valorization of its main by-product, crude glycerol, is imperative. Recently, Ustilago trichophora TZ1 was found to efficiently produce malic acid from glycerol. By adaptive laboratory evolution and medium optimization, titer and rate could be improved significantly. RESULTS: Here we report on the investigation of this strain in fed-batch bioreactors. With pH controlled at 6.5 (automatic NaOH addition), a titer of 142 +/- 1 g L(-1) produced at an overall rate of 0.54 +/- 0.00 g L(-1) h(-1) was reached by optimizing the initial concentrations of ammonium and glycerol. Combining the potential of bioreactors and CaCO3 as buffer system, we were able to increase the overall production rate to 0.74 +/- 0.06 g L(-1) h(-1) with a maximum production rate of 1.94 +/- 0.32 g L(-1) reaching a titer of 195 +/- 15 g L(-1). The initial purification strategy resulted in 90 % pure calcium malate as solid component. Notably, the fermentation is not influenced by an increased temperature of up to 37 degrees C, which reduces the energy required for cooling. However, direct acid production is not favored as at a lowered pH value of pH 4.5 the malic acid titer decreased to only 9 +/- 1 g L(-1). When using crude glycerol as substrate, only the product to substrate yield is decreased. The results are discussed in the context of valorizing glycerol with Ustilaginaceae. CONCLUSIONS: Combining these results reveals the potential of U. trichophora TZ1 to become an industrially applicable production host for malic acid from biodiesel-derived glycerol, thus making the overall biodiesel production process economically and ecologically more feasible. PMID- 27375776 TI - Leveraging 3D chemical similarity, target and phenotypic data in the identification of drug-protein and drug-adverse effect associations. AB - BACKGROUND: Drug-target identification is crucial to discover novel applications for existing drugs and provide more insights about mechanisms of biological actions, such as adverse drug effects (ADEs). Computational methods along with the integration of current big data sources provide a useful framework for drug target and drug-adverse effect discovery. RESULTS: In this article, we propose a method based on the integration of 3D chemical similarity, target and adverse effect data to generate a drug-target-adverse effect predictor along with a simple leveraging system to improve identification of drug-targets and drug adverse effects. In the first step, we generated a system for multiple drug target identification based on the application of 3D drug similarity into a large target dataset extracted from the ChEMBL. Next, we developed a target-adverse effect predictor combining targets from ChEMBL with phenotypic information provided by SIDER data source. Both modules were linked to generate a final predictor that establishes hypothesis about new drug-target-adverse effect candidates. Additionally, we showed that leveraging drug-target candidates with phenotypic data is very useful to improve the identification of drug-targets. The integration of phenotypic data into drug-target candidates yielded up to twofold precision improvement. In the opposite direction, leveraging drug-phenotype candidates with target data also yielded a significant enhancement in the performance. CONCLUSIONS: The modeling described in the current study is simple and efficient and has applications at large scale in drug repurposing and drug safety through the identification of mechanism of action of biological effects. PMID- 27375777 TI - Development and Validation of an Index to Predict Personal Prescription Drug Importation by Adults in the United States. AB - OBJECTIVE: Personal prescription drug importation (PPDI) is prevalent in the United States (U.S.) because of the high cost of U.S. medicines and lower cost of foreign equivalents. The practice carries the risk of exposure to counterfeit, adulterated, and substandard medicines. No known tools are available for predicting person-level PPDI risk. The objective of this study was to develop and validate a predictive PPDI index for policymakers, researchers, and clinicians. METHODS: Using 2011 and 2012 National Health Interview Survey (NHIS) data as the development and validation cohorts respectively, we identified predictors, built multivariable logistic regression models, and validated the index by comparing predicted risk of PPDI in the development cohort to the observed risk in the validation cohort. We assessed calibration using the Hosmer-Lemeshow goodness-of fit test and discrimination with C-statistics. The outcome measure was survey reported PPDI (1=yes; 0=no). KEY FINDINGS: In the development cohort, prevalence of PPDI in respondents with 0-2, 3, 4, 5-6, or >=7 risk factors were 0.32%, 0.57%, 1.09%, 2.95%, and 13.67% (C-statistic=0.78), and in the validation cohort, were 0.32%, 0.54%, 0.95%, 2.89%, and 10.80% (C-statistic=0.76). The Hosmer Lemeshow test indicated absence of a gross lack of fit (P=0.58) in the validation cohort. On the basis of index performance in the validation cohort, if an intervention to reduce importation were applied to all patients with scores of >=7, it would be applied to 31.1% of patients who engage in PPDI and 0.6% of the overall population. CONCLUSION: This predictive index accurately stratifies U.S. adults into groups at differential risk of PPDI and may provide value to those who are responsible for health policy and regulation of pharmaceutical importation. PMID- 27375778 TI - Nanostructure-Based Theranostic Systems. AB - This themed issue continues the focus on the recent developments of nanoscaled theranostic systems for early and accurate disease diagnosis, especially cancer diagnosis, as well as effective cancer treatment and management. PMID- 27375779 TI - Green Tea Catechin-Based Complex Micelles Combined with Doxorubicin to Overcome Cardiotoxicity and Multidrug Resistance. AB - Chemotherapy for cancer treatment has been demonstrated to cause some side effects on healthy tissues and multidrug resistance of the tumor cells, which greatly limits therapeutic efficacy. To address these limitations and achieve better therapeutic efficacy, combination therapy based on nanoparticle platforms provides a promising approach through delivering different agents simultaneously to the same destination with synergistic effect. In this study, a novel green tea catechin-based polyion complex (PIC) micelle loaded with doxorubicin (DOX) and ( )-Epigallocatechin-3-O-gallate (EGCG) was constructed through electrostatic interaction and phenylboronic acid-catechol interaction between poly(ethylene glycol)-block-poly(lysine-co-lysine-phenylboronic acid) (PEG-PLys/PBA) and EGCG. DOX was co-loaded in the PIC micelles through pi-pi stacking interaction with EGCG. The phenylboronic acid-catechol interaction endowed the PIC micelles with high stability under physiological condition. Moreover, acid cleavability of phenylboronic acid-catechol interaction in the micelle core has significant benefits for delivering EGCG and DOX to same destination with synergistic effects. In addition, benefiting from the oxygen free radicals scavenging activity of EGCG, combination therapy with EGCG and DOX in the micelle core could protect the cardiomyocytes from DOX-mediated cardiotoxicity according to the histopathologic analysis of hearts. Attributed to modulation of EGCG on P glycoprotein (P-gp) activity, this kind of PIC micelles could effectively reverse multidrug resistance of cancer cells. These results suggested that EGCG based PIC micelles could effectively overcome DOX induced cardiotoxicity and multidrug resistance. PMID- 27375780 TI - Supramolecular PEGylated Dendritic Systems as pH/Redox Dual-Responsive Theranostic Nanoplatforms for Platinum Drug Delivery and NIR Imaging. AB - Recently, self-assembling small dendrimers into supramolecular dendritic systems offers an alternative strategy to develop multifunctional nanoplatforms for biomedical applications. We herein report a dual-responsive supramolecular PEGylated dendritic system for efficient platinum-based drug delivery and near infrared (NIR) tracking. With a refined molecular/supramolecular engineering, supramolecular dendritic systems were stabilized by bioreducible disulfide bonds and endowed with NIR fluorescence probes, and PEGylated platinum derivatives coordinated onto the abundant peripheral groups of supramolecular dendritic templates to generate pH/redox dual-responsive theranostic supramolecular PEGylated dendritic systems (TSPDSs). TSPDSs markedly improved the pharmacokinetics and biodistribution of platinum-based drugs, owing to their stable nanostructures and PEGylated shells during the blood circulation. Tumor intracellular environment (low pH value and high glutathione concentration) could trigger the rapid disintegration of TSPDSs due to acid-labile coordination bonds and redox-cleavable disulfide linkages, and then platinum-based drugs were delivered into the nuclei to exert antitumor activity. In vivo antitumor treatments indicated TSPDSs not only provided high antitumor efficiency which was comparable to clinical cisplatin, but also reduced renal toxicity of platinum based drugs. Moreover, NIR fluorescence of TSPDSs successfully visualized in vitro and in vivo fate of nanoplatforms and disclosed the intracellular platinum delivery and pharmacokinetics. These results confirm tailor-made supramolecular dendritic system with sophisticated nanostructure and excellent performance is a promising candidate as smart theranostic nanoplatforms. PMID- 27375782 TI - HSP90 Inhibitor Encapsulated Photo-Theranostic Nanoparticles for Synergistic Combination Cancer Therapy. AB - Photodynamic therapy (PDT) is a promising non-invasive therapeutic modality that has been proposed for treating prostate cancer, but the procedure is associated with limited efficacy, tumor recurrence and photo-toxicity. In the present study, we proposed to develop a novel multifunctional nano-platform for targeted delivery of heat, reactive oxygen species (ROS) and heat shock protein 90 (Hsp90) inhibitor simultaneously for combination therapy against prostate cancer. This new nano-platform combines two newly developed entities: 1) a unique organic and biocompatible nanoporphyrin-based drug delivery system that can generate efficient heat and ROS simultaneously with light activation at the tumor sites for dual-modal photothermal- and photodynamic- therapy (PTT/PDT), and 2) new nano formulations of Hsp90 inhibitors that can decrease the levels of pro-survival and angiogenic signaling molecules induced by phototherapy, therefore, further sensitizing cancer cells to phototherapy. Furthermore, the nanoparticles have activatable near infrared (NIR) fluorescence for optical imaging to conveniently monitor the real-time drug delivery in both subcutaneous and orthotopic mouse models bearing prostate cancer xenograft. This novel multifunctional nano platform has great potential to improve the care of prostate cancer patients through targeted combination therapy. PMID- 27375781 TI - The Smart Drug Delivery System and Its Clinical Potential. AB - With the unprecedented progresses of biomedical nanotechnology during the past few decades, conventional drug delivery systems (DDSs) have been involved into smart DDSs with stimuli-responsive characteristics. Benefiting from the response to specific internal or external triggers, those well-defined nanoplatforms can increase the drug targeting efficacy, in the meantime, reduce side effects/toxicities of payloads, which are key factors for improving patient compliance. In academic field, variety of smart DDSs have been abundantly demonstrated for various intriguing systems, such as stimuli-responsive polymeric nanoparticles, liposomes, metals/metal oxides, and exosomes. However, these nanoplatforms are lack of standardized manufacturing method, toxicity assessment experience, and clear relevance between the pre-clinical and clinical studies, resulting in the huge difficulties to obtain regulatory and ethics approval. Therefore, such relatively complex stimulus-sensitive nano-DDSs are not currently approved for clinical use. In this review, we highlight the recent advances of smart nanoplatforms for targeting drug delivery. Furthermore, the clinical translation obstacles faced by these smart nanoplatforms have been reviewed and discussed. We also present the future directions and perspectives of stimuli sensitive DDS in clinical applications. PMID- 27375783 TI - Recent Developments of Liposomes as Nanocarriers for Theranostic Applications. AB - Liposomes are nanocarriers comprised of lipid bilayers encapsulating an aqueous core. The ability of liposomes to encapsulate a wide variety of diagnostic and therapeutic agents has led to significant interest in utilizing liposomes as nanocarriers for theranostic applications. In this review, we highlight recent progress in developing liposomes as nanocarriers for a) diagnostic applications to detect proteins, DNA, and small molecule targets using fluorescence, magnetic resonance, ultrasound, and nuclear imaging; b) therapeutic applications based on small molecule-based therapy, gene therapy and immunotherapy; and c) theranostic applications for simultaneous detection and treatment of heavy metal toxicity and cancers. In addition, we summarize recent studies towards understanding of interactions between liposomes and biological components. Finally, perspectives on future directions in advancing the field for clinical translations are also discussed. PMID- 27375784 TI - Accurate Quantification of Disease Markers in Human Serum Using Iron Oxide Nanoparticle-linked Immunosorbent Assay. AB - Accurate and reliable quantification of biomarkers in the blood is essential in disease screening and diagnosis. Here we describe an iron oxide nanoparticle (IONP)-linked immunosorbent assay (ILISA) for detecting biomolecules in human serum. Sandwich ILISA was optimized for the detection of four important serological markers, IgA, IgG, IgM, and C-reactive protein (CRP), and assessed with normal sera, simulated disease-state sera and the serum samples from patients infected with West Nile virus (WNV) or human herpes virus (HHV). Our study shows that using the detection assay formulated with 18.8 nm wustite nanocrystals, ILISA can achieve sub-picomolar detection sensitivity, and all four markers can be accurately quantified over a large dynamic range. In addition, ILISA is not susceptible to variations in operating procedures and shows better linearity and higher stability compared with ELISA, which facilitates its integration into detection methods suitable for point of care. Our results demonstrate that ILISA is a simple and versatile nanoplatform for highly sensitive and reliable detection of serological biomarkers in biomedical research and clinical applications. PMID- 27375785 TI - Targeted Nanotheranostics for Future Personalized Medicine: Recent Progress in Cancer Therapy. AB - Recently, many theranostic nanomaterials have been developed by integrating therapeutic and diagnostic agents in a single regimen. Real-time visualization of nano drug carrier biodistributions, drug release processes and therapeutic responses can provide critical information needed for dynamically optimizing treatment operations in a personalized manner in real time. This review highlights recent progresses in the development of multifunctional nanoparticles possessing both therapeutic and imaging functionalities for cancer therapy. The advantages of using nanoparticle platforms are discussed. Examples demonstrating various combinations of imaging and therapeutic modalities are highlighted. PMID- 27375786 TI - Phenylboronic Acid-Mediated Tumor Targeting of Chitosan Nanoparticles. AB - The phenylboronic acid-conjugated chitosan nanoparticles were prepared by particle surface modification. The size, zeta potential and morphology of the nanoparticles were characterized by dynamic light scattering, zeta potential measurement and transmission electron microscopy. The cellular uptake, tumor penetration, biodistribution and antitumor activity of the nanoparticles were evaluated by using monolayer cell model, 3-D multicellular spheroid model and H22 tumor-bearing mice. The incorporation of phenylboronic acid group into chitosan nanoparticles impart a surface charge-reversible characteristic to the nanoparticles. In vitro evaluation using 2-D and 3-D cell models showed that phenylboronic acid-decorated nanoparticles were more easily internalized by tumor cells compared to non-decorated chitosan nanoparticles, and could deliver more drug into tumor cells due to the active targeting effect of boronic acid group. Furthermore, the phenylboronic acid-decorated nanoparticles displayed a deeper penetration and persistent accumulation in the multicellular spheroids, resulting in better inhibition growth to multicellular spheroids than non-decorated nanoparticles. Tumor penetration, drug distribution and near infrared fluorescence imaging revealed that phenylboronic acid-decorated nanoparticles could penetrate deeper and accumulate more in tumor area than non-decorated ones. In vivo antitumor examination demonstrated that the phenylboronic acid-decorated nanoparticles have superior efficacy in restricting tumor growth and prolonging the survival time of tumor-bearing mice than free drug and drug-loaded chitosan nanoparticles. PMID- 27375788 TI - Serum Stability and Affinity Optimization of an M2 Macrophage-Targeting Peptide (M2pep). AB - Tumor associated macrophages (TAMs) are a major stromal component of the tumor microenvironment in several cancers. TAMs are a potential target for adjuvant cancer therapies due to their established roles in promoting proliferation of cancer cells, angiogenesis, and metastasis. We previously discovered an M2 macrophage-targeting peptide (M2pep) which was successfully used to target and deliver a pro-apoptotic KLA peptide to M2-like TAMs in a CT-26 colon carcinoma model. However, the effectiveness of in vivo TAM-targeting using M2pep is limited by its poor serum stability and low binding affinity. In this study, we synthesized M2pep derivatives with the goals of increasing serum stability and binding affinity. Serum stability evaluation of M2pepBiotin confirmed its rapid degradation attributed to exolytic cleavage from the N-terminus and endolytic cleavages at the W10/W11 and S16/K17 sites. N-terminal acetylation of M2pepBiotin protected the peptide against the exolytic degradation while W10w and K(17,18,19)k substitutions were able to effectively protect endolytic degradation at their respective cleavage sites. However, no tested amino acid changes at the W10 position resulted in both protease resistance at that site and retention of binding activity. Therefore, cyclization of M2pep was investigated. Cyclized M2pep better resisted serum degradation without compromising binding activity to M2 macrophages. During the serum stability optimization process, we also discovered that K9R and W10Y substitutions significantly enhanced binding affinity of M2pep. In an in vitro binding study of different M2pep analogs pre incubated in mouse serum, cyclic M2pep with K9R and W10Y modifications (cyclic M2pep(RY)) retained the highest binding activity to M2 macrophages over time due to its improved serum stability. Finally, we evaluated the in vivo accumulation of sulfo-Cy5-labeled M2pep and cyclic M2pep(RY) in both the CT-26 and 4T1 breast carcinoma models. Cyclic M2pep(RY) outperformed M2pep in both tumor localization and selective accumulation in M2-like TAMs. In conclusion, we report cyclic M2pep(RY) as our lead M2pep analog with improved serum stability and M2 macrophage-binding activity. Its enhanced utility as an in vivo M2-like-TAM targeting agent was demonstrated in two tumor models, and is expected to be applicable for other tumor models or in models of M2 macrophage-related diseases. PMID- 27375787 TI - Interventional Nanotheranostics of Pancreatic Ductal Adenocarcinoma. AB - Pancreatic ductal adenocarcinoma (PDAC) accounts for over 90% of all pancreatic cancer. Nanoparticles (NPs) offer new opportunities for image-guided therapy owing to the unique physicochemical properties of the nanoscale effect and the multifunctional capabilities of NPs. However, major obstacles exist for NP mediated cancer theranostics, especially in PDAC. The hypovascular nature of PDAC may impede the deposition of NPs into the tumor after systemic administration, and most NPs localize predominantly in the mononuclear phagocytic system, leading to a relatively poor tumor-to-surrounding-organ uptake ratio. Image guidance combined with minimally invasive interventional procedures may help circumvent these barriers to poor drug delivery of NPs in PDAC. Interventional treatments allow regional drug delivery, targeted vascular embolization, direct tumor ablation, and the possibility of disrupting the stromal barrier of PDAC. Interventional treatments also have potentially fewer complications, faster recovery, and lower cost compared with conventional therapies. This work is an overview of current image-guided interventional cancer nanotheranostics with specific attention given to their applications for the management of PDAC. PMID- 27375789 TI - Colorimetric TMPRSS2-ERG Gene Fusion Detection in Prostate Cancer Urinary Samples via Recombinase Polymerase Amplification. AB - TMPRSS2 (Exon 1)-ERG (Exon 4) is the most frequent gene fusion event in prostate cancer (PC), and is highly PC-specific unlike the current serum prostate specific antigen (PSA) biomarker. However, TMPRSS2-ERG levels are currently measured with quantitative reverse-transcription PCR (RT-qPCR) which is time-consuming and requires costly equipment, thus limiting its use in clinical diagnostics. Herein, we report a novel rapid, cost-efficient and minimal-equipment assay named "FusBLU" for detecting TMPRSS2-ERG gene fusions from urine. TMPRSS2-ERG mRNA was amplified by isothermal reverse transcription-recombinase polymerase amplification (RT-RPA), magnetically-isolated, and detected through horseradish peroxidase (HRP)-catalyzed colorimetric reaction. FusBLU was specific for TMPRSS2 ERG mRNA with a low visual detection limit of 10(5) copies. We also demonstrated assay readout versatility on 3 potentially useful platforms. The colorimetric readout was detectable by naked eye for a quick yes/no evaluation of gene fusion presence. On the other hand, a more quantitative TMPRSS2-ERG detection was achievable by absorbance/electrochemical measurements. FusBLU was successfully applied to 12 urinary samples and results were validated by gold-standard RT qPCR. We also showed that sediment RNA was likely the main source of TMPRSS2-ERG mRNA in urinary samples. We believe that our assay is a potential clinical screening tool for PC and could also have wide applications for other disease related fusion genes. PMID- 27375790 TI - Clinical Applications of NanoVelcro Rare-Cell Assays for Detection and Characterization of Circulating Tumor Cells. AB - Liquid biopsy of tumor through isolation of circulating tumor cells (CTCs) allows non-invasive, repetitive, and systemic sampling of disease. Although detecting and enumerating CTCs is of prognostic significance in metastatic cancer, it is conceivable that performing molecular and functional characterization on CTCs will reveal unprecedented insight into the pathogenic mechanisms driving lethal disease. Nanomaterial-embedded cancer diagnostic platforms, i.e., NanoVelcro CTC Assays represent a unique rare-cell sorting method that enables detection isolation, and characterization of CTCs in peripheral blood, providing an opportunity to noninvasively monitor disease progression in individual cancer patients. Over the past decade, a series of NanoVelcro CTC Assays has been demonstrated for exploring the full potential of CTCs as a clinical biomarker, including CTC enumeration, phenotyping, genotyping and expression profiling. In this review article, the authors will briefly introduce the development of three generations of NanoVelcro CTC Assays, and highlight the clinical applications of each generation for various types of solid cancers, including prostate cancer, pancreatic cancer, lung cancer, and melanoma. PMID- 27375791 TI - Generating Cell Targeting Aptamers for Nanotheranostics Using Cell-SELEX. AB - Detecting and understanding changes in cell conditions on the molecular level is of great importance for the accurate diagnosis and timely therapy of diseases. Cell-based SELEX (Systematic Evolution of Ligands by EXponential enrichment), a foundational technology used to generate highly-specific, cell-targeting aptamers, has been increasingly employed in studies of molecular medicine, including biomarker discovery and early diagnosis/targeting therapy of cancer. In this review, we begin with a mechanical description of the cell-SELEX process, covering aptamer selection, identification and identification, and aptamer characterization; following this introduction is a comprehensive discussion of the potential for aptamers as targeting moieties in the construction of various nanotheranostics. Challenges and prospects for cell-SELEX and aptamer-based nanotheranostic are also discussed. PMID- 27375792 TI - In Vivo Visualization of Tumor Antigen-containing Microparticles Generated in Fluorescent-protein-elicited Immunity. AB - In vivo optical spatio-temporal imaging of the tumor microenvironment is useful to explain how tumor immunotherapies work. However, the lack of fluorescent antigens with strong immunogenicity makes it difficult to study the dynamics of how tumors are eliminated by any given immune response. Here, we develop an effective fluorescent model antigen based on the tetrameric far-red fluorescent protein KatushkaS158A (tfRFP), which elicits both humoral and cellular immunity. We use this fluorescent antigen to visualize the dynamic behavior of immunocytes as they attack and selectively eliminate tfRFP-expressing tumors in vivo; swarms of immunocytes rush toward tumors with high motility, clusters of immunocytes form quickly, and numerous antigen-antibody complexes in the form of tfRFP(+) microparticles are generated in the tumor areas and ingested by macrophages in the tumor microenvironment. Therefore, tfRFP, as both a model antigen and fluorescent reporter, is a useful tool to visualize specific immune responses in vivo. PMID- 27375794 TI - Explaining the high PM10 concentrations observed in Polish urban areas. AB - The main goal of this paper is to identify the drivers responsible for the high particulate matter concentrations observed in recent years in several urban areas in Poland. The problem was investigated using air quality and meteorological data from routine monitoring network, air mass back trajectories and multivariate statistical modelling. Air pollution in central and southern part of the country was analysed and compared with this in northern-eastern "The Green Lungs of Poland" region. The analysis showed that in all investigated locations, there is a clear annual cycle of observed concentrations, closely following temperature heating cycles, with the highest concentrations noted in January. However, the main drivers differ along the country, being either connected with regional background pollution (in the central part of the country) or with local emission sources (in the southern part). The occurrence of high PM10 concentrations is most commonly associated with the influence of high-pressure systems that brought extremely cold and stable air masses form East or South of Europe. During analysed episodes, industrial point sources had the biggest (up to 70-80 %) share in PM10 levels on the days with maximum PM pollution, while remote and residential/traffic sources determined the air quality in the early stages of the episodes. Principal component analysis (PCA) shows that secondary inorganic aerosols account for long-range transported pollution, As, Cd, Pb and Zn for industrial point sources, while Cr and Cu for residential and traffic sources of PM10, respectively. PMID- 27375793 TI - In Vivo Targeting of Metabolically Labeled Cancers with Ultra-Small Silica Nanoconjugates. AB - Unnatural sugar-mediated metabolic labeling of cancer cells, coupled with efficient Click chemistry, has shown great potential for in vivo imaging and cancer targeting. Thus far, chemical labeling of cancer cells has been limited to the small-sized azido groups, with the large-sized and highly hydrophobic dibenzocyclooctyne (DBCO) being correspondingly used as the targeting ligand. However, surface modification of nanomedicines with DBCO groups often suffers from low ligand density, difficult functionalization, and impaired physiochemical properties. Here we report the development of DBCO-bearing unnatural sugars that could directly label LS174T colon cancer cells with DBCO groups and subsequently mediate cancer-targeted delivery of azido-modified silica nanoconjugates with easy functionalization and high azido density in vitro and in vivo. This study, for the first time, demonstrates the feasibility of metabolic labeling of cancer cells with large-sized DBCO groups for subsequent, efficient targeting of azido modified nanomedicines. PMID- 27375795 TI - Size-segregated urban particulate matter: mass closure, chemical composition, and primary and secondary matter content. AB - Forty-nine components of ambient particulate matter (PM) in size-fractionated PM were investigated at an urban background site in Katowice (Silesian Agglomeration in Southern Poland) in the non-heating season of 2012. PM was analyzed for two groups of carbon compounds (organic (OC) and elemental (EC) carbon, Lab OC-EC Aerosol Analyzer), five major water-soluble ions (NH4+, Cl-, SO42-, NO3-, and Na+ contents in PM water extracts, ion chromatography), 26 elements (X-ray fluorescence spectrometry), and 16 polycyclic aromatic hydrocarbons (PAHs, gas chromatography). The distributions of the masses of these components among 13 basic PM fractions were determined, and chemical mass closure was checked for each of these fractions separately. The particles having their aerodynamic diameters in the interval 0.03-0.26 MUm, the fraction PM0.03-0.26, contributed about 13 % to the total PM mass. This PM fraction consisted of primary particles predominantly composed of various inorganic compounds, primary organic compounds, and, in lesser amounts, of elemental carbon, secondary ions, and secondary organic compounds. The second particle fraction, PM0.26-1.6, consisted mainly of secondary matter, and its mass contribution to the total PM mass was about 59 %. The third fraction, PM1.6-40, was a fraction of coarse particles composed of mineral/soil and organic matter and elemental carbon. It contributed to the PM mass about 28 %. For each of PM0.03-0.26, PM0.26-1.6, and PM1.6-40, the health hazard from its 16 PAH contents was determined by computing toxicity factors. PM0.26-1.6 posed the greatest health hazard from the mixture of the 16 PAHs that it contained, PM1.6-40 was the next, and the hazard from the PM0.03-0.26-bound 16 PAHs was the smallest. The molecular diagnostic ratios computed for these three fractions were specific for coal and wood combustion; some indicated the road traffic effects. PMID- 27375796 TI - Cancer in Japan: Prevalence, prevention and the role of heterocyclic amines in human carcinogenesis. AB - In this article, three topics are being studied in order to understand the present state of cancer in Japan. First, the statistics on cancer mortality indicates that the mortality from cancer in young individuals has been decreasing during the last 50 years, although the total mortality from cancer has been steadily and steeply increasing. Second, epidemiological analyses of cancer causes in Japan indicated that 50 % of cancer cases are preventable, and that prevention of infection and refraining from tobacco smoking will reduce cancer mortality by about 40 %. Third, mutagenic/carcinogenic heterocyclic amines present in cooked meat/fish have been suggested to be carcinogenic in humans in many epidemiological studies carried out in Japan and other countries. PMID- 27375797 TI - What causes human cancer? Approaches from the chemistry of DNA damage. AB - To prevent human cancers, environmental mutagens must be identified. A common mechanism of carcinogenesis is DNA damage, and thus it is quite possible that environmental mutagens can be trapped as adducts by DNA components. It is also important to identify new types of DNA damaging reactions and clarify their mechanisms. In this paper, I will provide typical examples of our efforts to identify DNA damage by environmental agents, from chemistry-based studies. 1) Oxidative DNA damage: 8-Hydroxydeoxyguanosine (8-OHdG, 8-oxodG) was discovered during a structural study of DNA modifications caused in vitro by heating glucose, which was used as a model of cooked foods. We found that various oxygen radical-forming agents induced the formation of 8-OHdG in DNA, in vitro and in vivo. Analyses of the urinary 8-OHdG levels are useful to assess the extent of oxidative DNA damage in a human population. 2) Lipid peroxide-derived DNA adducts: We searched for mutagens that react with deoxynucleosides, in model systems of lipid peroxidation. The reaction mixtures were analyzed by high performance liquid chromatography (HPLC), and we discovered various lipid peroxide-derived mutagens, including new mutagens. Some of these adducts were detected in human DNA. These mutagens may be involved in lipid peroxide-related cancers. 3) Methylation of cytosine by free radicals: Methylation of the cytosine C-5 position is an important mechanism of carcinogenesis, in addition to gene mutations. However, the actual mechanisms of de novo methylation in relation to environmental agents are not clear. We found that cytosine C-5 methylation occurred by a free radical mechanism. The possible role of this radical-induced DNA methylation in carcinogenesis will be discussed, in relation to the presently accepted concept of cancer epigenetics. In these studies, chemical analyses of the adducts formed in model reactions led to the discoveries of new mutagens and important types of DNA modifications, which seem to be involved in human carcinogenesis. PMID- 27375798 TI - Aortic Aneurysm: Etiopathogenesis and Clinicopathologic Correlations. AB - Aortic aneurysm (AA) is one of the life-threatening aortic diseases, leading to aortic rupture of any cause including atherosclerotic and non-atherosclerotic diseases. AA is diagnosed in a variable proportion of patients with dilated aorta by imaging modality. The etiopathogenesis of AA remains unclear in many aortic diseases. Furthermore, although it may be difficult to explain all phenotypes of patients even if genetic mutation could be identified in some proteins such as smooth muscle cell alpha-actin (ACTA2), myosin heavy chain 11 (MYH11) or SMAD3, individualized consideration of these factors in each patient is essential on the basis of clinicopathological characteristics. PMID- 27375799 TI - Long-Term Results of Obturator Bypass. AB - OBJECTIVE: We evaluated the long-term outcomes of obturator bypass. MATERIAL AND METHODS: A total of 16 patients (13 males and 3 females; 17 limbs) who underwent obturator bypass surgery at our department between April 1995 and March 2008 were included. RESULTS: Their ages ranged from 50 to 90 with a mean of 74 years. Inguinal infections observed in the 16 patients consisted of vascular graft infections in 13 patients, hemostatic device infections following endovascular therapy in two patients, and femoral artery infections following coronary angiography in one patient. The cumulative patency rate was 69% for 3 years and 43% for 5 years. The cumulative survival rate was 64% for 3 years and 55% for 5 years. CONCLUSION: Obturator bypass surgery was successfully performed with favorable results for arterial infections and vascular graft infections in the inguinal region. PMID- 27375800 TI - Clinical Features and Developing Risks of Saphenous Vein Thrombophlebitis. AB - We evaluated the clinical features and the risks of 14 patients with 14 limbs affected by saphenous vein thrombophlebitis from April 2007 to May 2013 and compared the results with patients undergoing operative repair of varicose veins (127 patients, 193 limbs) during the study period. The frequency of patients with a body mass index over 25 (78.6% vs. 35.3%, p = 0.0018), varicose change in the saphenous vein (78.6% vs. 6.2%, p <0.0001), and concurrent thrombosis in another vein (50.0% vs. 7.1%, p <0.0001) were all significantly higher than those of the patients under operative repair for varicose veins. These patients with clinical features above may be at an elevated risk of thrombophlebitis of the saphenous trunk. (This article is a translation of J Jpn Coll Angiol 2014; 54: 151-157). PMID- 27375801 TI - Does Triplex Vascular Prosthesis Contribute to Reducing the Inflammatory Reaction after Surgical Repair of Abdominal Aortic Aneurysms? AB - Our aim was to evaluate whether a Triplex vascular prosthesis could contribute to reducing postoperative inflammation after surgical abdominal aortic aneurysm (AAA) repair retrospectively. Between July 2011 and December 2013, a Triplex vascular prosthesis was used in 22 patients (group T) and a coated vascular prosthesis in 18 patients (group H) during AAA repair surgery. Body temperature (BT), white blood cell (WBC) count, and C-reactive protein (CRP) level for 5 days were assessed. There was no hospital death in both groups. During the first 2 days after surgery the BT was higher in group T than in group H reaching its maximum on POD 2. On POD 5, it was similar (p = 0.4850). The postoperative WBC count was higher in group H than in group T. It reached its maximum on POD 1 and it was similar in both groups on POD 5 (p = 0.1870). The CRP value increased postoperatively in both groups, peaking during PODs 2 or 3. On POD 5, it was lower in group H than in group T (p = 0.0415). We could not confirm the superiority of Triplex vascular prostheses to other coated vascular prostheses in inflammatory reactions. PMID- 27375802 TI - Effects of Preoperative Glycyrrhizin Infusion for the Prevention of Venous Thrombosis on the Tissue Expression of Antithrombin in a Rat Model. AB - OBJECTIVE: Using a thrombus model prepared by ligation of the inferior vena cava (IVC), the influences of the glycoside, glycyrrhizin, on plasma antithrombin levels and antithrombin mRNA expression levels in the liver and IVC with the inhibition of venous thrombosis were investigated. MATERIALS AND METHODS: The rat IVC was exposed and ligated for 24 h immediately after the intravenous administration of 300 mg/kg glycyrrhizin. Among antithrombotic drugs, the Xa inhibitor, fondaparinux sodium, was used as a control drug. RESULTS: The mean thrombus weight was significantly smaller in the glycyrrhizin-treated group (18.3 mg) than in the saline-treated group (34.3 mg). In contrast, the inhibition of thrombosis was not observed in the fondaparinux-treated group. Antithrombin mRNA expression levels in the liver were significantly higher in the ligated groups than in the baseline control group. The mean plasma antithrombin level was significantly lower in the glycyrrhizin group (96.6%) than in the saline group (114.4%), but was not significantly different from that in the baseline control group (102.4%). CONCLUSION: The pretreatment with glycyrrhizin inhibited venous thrombosis, and antithrombin mRNA expression levels in the liver and IVC as well as plasma antithrombin levels were significantly lower than those in the saline group. PMID- 27375803 TI - Late Sac Behavior after Endovascular Aneurysm Repair for Abdominal Aortic Aneurysm. AB - BACKGROUND: Sac behavior after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAAs) is considered as a surrogate for the risk of late rupture. The purpose of the study is to assess the sac behavior of AAAs after EVAR. METHODS AND RESULTS: Late sac enlargement (LSE) (>=5 mm) and late sac shrinkage (LSS) (>=5 mm) were analyzed in 589 consecutive patients who were registered at 14 national centers in Japan. The proportions of patients who had LSE at 1, 3 and 5 years were 2.6% +/- 0.7%, 10.0% +/- 1.6% and 19.0% +/- 2.9%. The proportions of patients who had LSS at 1, 3 and 5 years were 50.1% +/- 0.7%, 59.2% +/- 2.3% and 61.7% +/- 2.7%. Multiple logistic regression analysis identified two variables as a risk factor for LSE; persistent endoleak (Odds ratio 9.56 (4.84-19.49), P <0.001) and low platelet count (Odds ratio 0.92 (0.86 0.99), P = 0.0224). The leading cause of endoleak in patients with LSE was type II. CONCLUSIONS: The incidence of LSE is not negligible over 5 year period. Patients with persistent endoleak and/or low platelet count should carefully be observed for LSE. CLINICAL TRIAL REGISTRATION: UMIN-CTR (UMIN000008345). PMID- 27375804 TI - Successful Treatment of Iatrogenic Subclavian Artery Pseudoaneurysm by Ultrasound Guided Thrombin Injection. AB - Ultrasound-guided thrombin injection has been well described as a safe and effective treatment for pseudoaneurysms of the femoral artery. However, cases for subclavian artery pseudoaneurysm are rare. An 82-year-old man developed an iatrogenic right subclavian artery pseudoaneurysm. The pseudoaneurysm, which was partially thrombosed, was successfully treated by ultrasound-guided percutaneous thrombin injection. A trial injection with saline under color Doppler ultrasonography was helpful for confirming that the tip of the needle was in the sac with blood flow in the partially thrombosed pseudoaneurysm. Ultrasound-guided thrombin injection can be the first treatment of choice to treat subclavian artery pseudoaneurysm. PMID- 27375805 TI - Endovascular Repair by Graft-to-Graft Bridging in a Patient with Marfan Syndrome. AB - We report a case of chronic aortic dissection in a patient with Marfan syndrome in which we performed thoracic endovascular repair after aortic root replacement, total arch replacement with open stent grafting and thoracoabdominal aortic repair. We consider that endovascular repair of the dissected descending aorta in a patient with Marfan syndrome can be effective when graft-to-graft bridging is performed as the "finishing procedure". PMID- 27375806 TI - Axillobifemoral Bypass for Aortitis Syndrome in a Living-Donor Liver Transplant Patient. AB - A 64-year-old female patient with aortitis syndrome presented with progressive intermittent claudication for 6 months. Her medical history was notable for living-donor liver transplantation for primary biliary cirrhosis 4-years prior and chronic immunosuppressive therapy. Evaluation included normal laboratory examination, and contrast-enhanced computed tomography angiography which demonstrated severely calcified descending aorta with high-grade stenosis below the diaphragm. The patient was treated by axillobifemoral bypass using an 8-mm ringed expanded polytetrafluoroethylene graft under general anesthesia. Medical management included decreased preoperative doses of immunosuppressants and predonisolone, which were resumed after the operation, and chronic anticoagulation. There were no postoperative complications. PMID- 27375807 TI - A Case of Dissection and Rupture of the Innominate Artery in Acute Type A Aortic Dissection. AB - We report the case of a 59-year-old male presenting with dissection and rupture of the innominate artery with acute type A aortic dissection. We performed total arch replacement via median sternotomy with extension into the right side of the neck. The innominate artery was reconstructed just proximal to the bifurcation of the right subclavian artery and common carotid artery using the 1st limb of a 4 branched graft. This case illustrates an unusual aspect of an isolated innominate artery rupture in the absence of aortic rupture in acute type A aortic dissection. PMID- 27375808 TI - Unique Technique for Open Surgical Repair after Failed Endovascular Aneurysm Repair with Proximal Anastomoses. AB - Endovascular aortic aneurysm repair (EVAR) has revolutionized the management of abdominal aortic aneurysms (AAAs), with lower perioperative morbidity and mortality compared to conventional surgical repair. However, late secondary re interventions after EVAR are still needed before aneurysm rupture in many cases. A patient with impending rupture of an AAA associated with a type I endoleak 7 years after EVAR who was successfully treated with a unique technique of fixation of the proximal aortic neck taking into account the structure of the stent graft is reported. This technique offers a safe solution to late open conversion after failed EVAR. PMID- 27375809 TI - Endovascular Stenting for Non-Traumatic Celiac Artery Stenosis Following Pancreatoduodenectomy. AB - Postoperative celiac artery stenosis (CAS) rarely occurs in the absence of vascular injury or pseudoaneurysm after pancreatoduodenectomy (PD). Because of its low incidence, the optimal treatment for non-traumatic postoperative CAS is unknown. Here, we show a case of CAS possibly due to exacerbated median arcuate ligament compression after PD. The purpose of this report is to describe this rare complication and its successful endovascular treatment with review of literatures. PMID- 27375810 TI - Recanalization of a Heavily Calcified Chronic Total Occlusion in a Femoropopliteal Artery Using a Wingman Crossing Catheter. AB - We present a 77-year-old female with heavily calcified chronic total occlusions (CTO) in a superficial femoral artery treated by endovascular therapy using a Wingman crossing catheter, which is an over-the-wire catheter with a metallic blade, controlled manually. The blade could probe and track the calcified cap of CTO, wherein any hydrophilic guidewires or looped wires could not penetrate. Moreover, the Wingman could proceed through the occlusion and introduce a guidewire into distal intramedial lumen as a support catheter. Finally, wire crossing was achieved using a bi-directional approach. The Wingman can be a simple solution for crossing calcified peripheral CTO. PMID- 27375811 TI - 7(th) Asian PAD Workshop. PMID- 27375812 TI - Morphological plasticity of bacteria-Open questions. AB - Morphological plasticity of bacteria is a cryptic phenomenon, by which bacteria acquire adaptive benefits for coping with changing environments. Some environmental cues were identified to induce morphological plasticity, but the underlying molecular mechanisms remain largely unknown. Physical and chemical factors causing morphological changes in bacteria have been investigated and mostly associated with potential pathways linked to the cell wall synthetic machinery. These include starvation, oxidative stresses, predation effectors, antimicrobial agents, temperature stresses, osmotic shock, and mechanical constraints. In an extreme scenario of morphological plasticity, bacteria can be induced to be shapeshifters when the cell walls are defective or deficient. They follow distinct developmental pathways and transform into assorted morphological variants, and most of them would eventually revert to typical cell morphology. It is suggested that phenotypic heterogeneity might play a functional role in the development of morphological diversity and/or plasticity within an isogenic population. Accordingly, phenotypic heterogeneity and inherited morphological plasticity are found to be survival strategies adopted by bacteria in response to environmental stresses. Here, microfluidic and nanofabrication technology is considered to provide versatile solutions to induce morphological plasticity, sort and isolate morphological variants, and perform single-cell analysis including transcriptional and epigenetic profiling. Questions such as how morphogenesis network is modulated or rewired (if epigenetic controls of cell morphogenesis apply) to induce bacterial morphological plasticity could be resolved with the aid of micro-nanofluidic platforms and optimization algorithms, such as feedback system control. PMID- 27375813 TI - Refinement of current monitoring methodology for electroosmotic flow assessment under low ionic strength conditions. AB - Current monitoring is a well-established technique for the characterization of electroosmotic (EO) flow in microfluidic devices. This method relies on monitoring the time response of the electric current when a test buffer solution is displaced by an auxiliary solution using EO flow. In this scheme, each solution has a different ionic concentration (and electric conductivity). The difference in the ionic concentration of the two solutions defines the dynamic time response of the electric current and, hence, the current signal to be measured: larger concentration differences result in larger measurable signals. A small concentration difference is needed, however, to avoid dispersion at the interface between the two solutions, which can result in undesired pressure driven flow that conflicts with the EO flow. Additional challenges arise as the conductivity of the test solution decreases, leading to a reduced electric current signal that may be masked by noise during the measuring process, making for a difficult estimation of an accurate EO mobility. This contribution presents a new scheme for current monitoring that employs multiple channels arranged in parallel, producing an increase in the signal-to-noise ratio of the electric current to be measured and increasing the estimation accuracy. The use of this parallel approach is particularly useful in the estimation of the EO mobility in systems where low conductivity mediums are required, such as insulator based dielectrophoresis devices. PMID- 27375814 TI - Field amplified sample stacking of amyloid beta (1-42) oligomers using capillary electrophoresis. AB - Oligomeric forms of the amyloid beta (Abeta) protein have been indicated to be an important factor in the development of Alzheimer's disease (AD). Since the oligomeric forms of Abeta can vary in size and conformation, it is vital to understand the early stages of Abeta aggregation in order to improve the care and treatment of patients with AD. This is the first study to determine the effect of field amplified sample stacking (FASS) on the separation of oligomeric forms of Abeta1-42 using capillary electrophoresis (CE) with ultraviolet (UV) detection. UV-CE was able to separate two different species of Abeta1-42 oligomers (<7 mers and 7-22 mers). Although FASS required the use of a higher ionic strength buffer, Abeta1-42 oligomers had the same aggregation behavior as under the non-FASS conditions with only small changes in the amounts of oligomers observed. In general, FASS provided smaller peak widths (>75% average reduction) and increased peak heights (>60% average increase) when compared to non-FASS conditions. UV-CE with FASS also provided higher resolution between the Abeta1-42 oligomers for all aggregation time points studied. In addition, Congo red and Orange G inhibition studies were used to help evaluate the conformation of the observed species. This work demonstrates the ability of UV-CE employing FASS to provide higher resolution between oligomeric forms of Abeta1-42 without significantly altering their aggregation. PMID- 27375815 TI - Modelling of electrokinetic phenomena for capture of PEGylated ribonuclease A in a microdevice with insulating structures. AB - Synthesis of PEGylated proteins results in a mixture of protein-polyethylene glycol (PEG) conjugates and the unreacted native protein. From a ribonuclease A (RNase A) PEGylation reaction, mono-PEGylated RNase A (mono-PEG RNase A) has proven therapeutic effects against cancer, reason for which there is an interest in isolating it from the rest of the reaction products. Experimental trapping of PEGylated RNase A inside an electrokinetically driven microfluidic device has been previously demonstrated. Now, from a theoretical point of view, we have studied the electrokinetic phenomena involved in the dielectrophoretic streaming of the native RNase A protein and the trapping of the mono-PEG RNase A inside a microfluidic channel. To accomplish this, we used two 3D computational models, a sphere and an ellipse, adapted to each protein. The effect of temperature on parameters related to trapping was also studied. A temperature increase showed to rise the electric and thermal conductivities of the suspending solution, hindering dielectrophoretic trapping. In contrast, the dynamic viscosity of the suspending solution decreased as the temperature rose, favoring the dielectrophoretic manipulation of the proteins. Also, our models were able to predict the magnitude and direction of the velocity of both proteins indicating trapping for the PEGylated conjugate or no trapping for the native protein. In addition, a parametric sweep study revealed the effect of the protein zeta potential on the electrokinetic response of the protein. We believe this work will serve as a tool to improve the design of electrokinetically driven microfluidic channels for the separation and recovery of PEGylated proteins in one single step. PMID- 27375816 TI - Enrichment of diluted cell populations from large sample volumes using 3D carbon electrode dielectrophoresis. AB - Here, we report on an enrichment protocol using carbon electrode dielectrophoresis to isolate and purify a targeted cell population from sample volumes up to 4 ml. We aim at trapping, washing, and recovering an enriched cell fraction that will facilitate downstream analysis. We used an increasingly diluted sample of yeast, 10(6)-10(2) cells/ml, to demonstrate the isolation and enrichment of few cells at increasing flow rates. A maximum average enrichment of 154.2 +/- 23.7 times was achieved when the sample flow rate was 10 MUl/min and yeast cells were suspended in low electrically conductive media that maximizes dielectrophoresis trapping. A COMSOL Multiphysics model allowed for the comparison between experimental and simulation results. Discussion is conducted on the discrepancies between such results and how the model can be further improved. PMID- 27375817 TI - Insulator-based dielectrophoretic diagnostic tool for babesiosis. AB - Babesia species are obligate intraerythrocytic tick-borne protozoan parasites that are the etiologic agents of babesiosis, a potentially life-threatening, malaria-like illness in humans and animals. Babesia-infected people have been known to suffer from complications including liver problems, severe hemolytic anemia, and kidney failure. As reported by the Food and Drug Administration, 38% of mortality cases observed in transfusion recipients were associated with transfusion transmitted diseases of which babesiosis is the chief culprit. As of now, no tests have been licensed yet for screening blood donors for babesiosis. Current diagnostic tools for babesiosis including enzyme-linked immunosorbent assay, fluorescence in situ hybridization, and polymerase chain reaction are expensive and burdened with multifarious shortcomings. In this research, a low cost, high-specificity, quick, and easy-to-use insulator-based dielectrophoretic diagnostic tool is developed for characterizing and concentrating Babesia infected cells in their homogenous mixture with healthy cell population. In this work, a mixture of Babesia-infected (varying parasitemia) and healthy red blood cells (RBCs or erythrocytes) was exposed to non-uniform electric fields in a fabricated microfluidic platform to manipulate and sort the Babesia-infected cells within a minute. At DC voltage configurations of 10 V and 0/6 V in the inlet and the two outlet channels, respectively, the diseased cells were seen to flow in a direction different from the healthy RBCs. Bright field and fluorescence microscopy were utilized to present qualitative differentiation of the healthy erythrocytes from the infected cells. The proposed micro device platform was able to enrich RBCs from 0.1% to ~70% parasitemia. This device, when finally developed into a point-of-care diagnostic chip, would enhance the detection of Babesia-infected erythrocytes and as well serve as a precursor to babesiosis vaccine development. PMID- 27375818 TI - Design of a hybrid advective-diffusive microfluidic system with ellipsometric detection for studying adsorption. AB - Establishing and maintaining concentration gradients that are stable in space and time is critical for applications that require screening the adsorption behavior of organic or inorganic species onto solid surfaces for wide ranges of fluid compositions. In this work, we present a design of a simple and compact microfluidic device based on steady-state diffusion of the analyte, between two control channels where liquid is pumped through. The device generates a near linear distribution of concentrations. We demonstrate this via experiments with dye solutions and comparison to finite-element numerical simulations. In a subsequent step, the device is combined with total internal reflection ellipsometry to study the adsorption of (cat)ions on silica surfaces from CsCl solutions at variable pH. Such a combined setup permits a fast determination of an adsorption isotherm. The measured optical thickness is compared to calculations from a triple layer model for the ion distribution, where surface complexation reactions of the silica are taken into account. Our results show a clear enhancement of the ion adsorption with increasing pH, which can be well described with reasonable values for the equilibrium constants of the surface reactions. PMID- 27375819 TI - Multiplexed immunosensing and kinetics monitoring in nanofluidic devices with highly enhanced target capture efficiency. AB - Nanofluidic devices promise high reaction efficiency and fast kinetic responses due to the spatial constriction of transported biomolecules with confined molecular diffusion. However, parallel detection of multiple biomolecules, particularly proteins, in highly confined space remains challenging. This study integrates extended nanofluidics with embedded protein microarray to achieve multiplexed real-time biosensing and kinetics monitoring. Implementation of embedded standard-sized antibody microarray is attained by epoxy-silane surface modification and a room-temperature low-aspect-ratio bonding technique. An effective sample transport is achieved by electrokinetic pumping via electroosmotic flow. Through the nanoslit-based spatial confinement, the antigen antibody binding reaction is enhanced with ~100% efficiency and may be directly observed with fluorescence microscopy without the requirement of intermediate washing steps. The image-based data provide numerous spatially distributed reaction kinetic curves and are collectively modeled using a simple one dimensional convection-reaction model. This study represents an integrated nanofluidic solution for real-time multiplexed immunosensing and kinetics monitoring, starting from device fabrication, protein immobilization, device bonding, sample transport, to data analysis at Peclet number less than 1. PMID- 27375820 TI - Stability and efficacy of synthetic cationic antimicrobial peptides nebulized using high frequency acoustic waves. AB - Surface acoustic wave (SAW), a nanometer amplitude electroelastic wave generated and propagated on low-loss piezoelectric substrates (such as LiNbO3), is an extremely efficient solid-fluid energy transfer mechanism. The present study explores the use of SAW nebulization as a solution for effective pulmonary peptide delivery. In vitro deposition characteristics of the nebulized peptides were determined using a Next Generation Cascade Impactor. 70% of the peptide laden aerosols generated were within a size distribution favorable for deep lung distribution. The integrity of the nebulized peptides was found to be retained, as shown via mass spectrometry. The anti-mycobacterial activity of the nebulized peptides was found to be uncompromised compared with their non-nebulized counterparts, as demonstrated by the minimum inhibition concentration and the colony forming inhibition activity. The peptide concentration and volume recoveries for the SAW nebulizer were significantly higher than 90% and found to be insensitive to variation in the peptide sequences. These results demonstrate the potential of the SAW nebulization platform as an effective delivery system of therapeutic peptides through the respiratory tract to the deep lung. PMID- 27375821 TI - Increasing local density and purity of molecules/bacteria on a sensing surface from diluted blood using 3D hybrid electrokinetics. AB - We present a long-range and selective nanocolloid/molecular/bacteria concentrator based on 3D hybrid AC electrokinetics (ACEK) that includes AC dielectrophoresis (DEP) and biased AC electroosmosis (ACEO). Through a convergency comb-shaped electrode design, this long-range ACEO allows the effective transport of a high number of targets into the centre of the detection zone. In the proposed 3D hybrid electrokinetics model, 3D ACEO provides long-range transportation, and the 3D DEP provides an effective separation mechanism. Thus, detection targets ranging from nanoscale to micrometers could be selectively concentrated long range from diluted blood. The proposed design was used for selectively concentrating nanocolloids and bacteria in the diluted blood sample, respectively. Compared to a 3D short-range dipolar electrode configuration, the detection limit of long-range 3D convergency tripolar electrode configuration is one order of magnitude higher. The result also shows that the 3D hybrid ACEK demonstrated a higher purity of any plane above the electrode, which compared positively to the same design of a 2D hybrid ACEK. The concentration factor of the proposed 3D hybrid electrokinetics device increased by several orders of local density and raised the local purity at least 6 orders (from 0.05% to greater than 99.9%). The chip is capable of making a DNA/protein/bacterial aggregate characterized by high local density and purity for further molecular and bacteria detection/analysis. PMID- 27375822 TI - Student-led microfluidics lab practicals: Improving engagement and learning outcomes. AB - Microfluidics has shown rapid growth in both research and development and offers significant commercialisation potential for biomedical and diagnostic applications in particular. However, there is a lack of awareness of microfluidics outside the field of study, and few dedicated educational programmes are available. While many topics incorporate microfluidics teaching, reported initiatives in the literature have not yet taken a problem based learning (PBL) approach to the delivery of practical sessions. The educational approaches already reported typically focus upon production and testing of pre determined device designs for specific applications, using a "recipe" style of lab teaching. Here, we report on a newly designed lab section of a microfluidic teaching component utilising problem based learning (PBL) to involve the students in all aspects of design, manufacture, and performance characterisation of microfluidic solutions. Details of the lab design and development are given enabling others to replicate the lab structure described here or use it as a basis for the design of similar PBL microfluidics teaching labs. A key focus of the work has been the evaluation of the student experience, and the results of a survey indicate a high degree of student satisfaction and skills development due to the PBL approach. PMID- 27375823 TI - Erratum: "Characterization of the near-field and convectional transport behavior of micro and nanoparticles in nanoscale plasmonic optical lattices" [Biomicrofluidics 10, 034102 (2016)]. PMID- 27375824 TI - Micro-scale extensional rheometry using hyperbolic converging/diverging channels and jet breakup. AB - Understanding the elongational rheology of dilute polymer solutions plays an important role in many biological and industrial applications ranging from microfluidic lab-on-a-chip diagnostics to phenomena such as fuel atomization and combustion. Making quantitative measurements of the extensional viscosity for dilute viscoelastic fluids is a long-standing challenge and it motivates developments in microfluidic fabrication techniques and high speed/strobe imaging of millifluidic capillary phenomena in order to develop new classes of instruments. In this paper, we study the elongational rheology of a family of dilute polymeric solutions in two devices: first, steady pressure-driven flow through a hyperbolic microfluidic contraction/expansion and, second, the capillary driven breakup of a thin filament formed from a small diameter jet ([Formula: see text]). The small length scale of the device allows very large deformation rates to be achieved. Our results show that in certain limits of low viscosity and elasticity, jet breakup studies offer significant advantages over the hyperbolic channel measurements despite the more complex implementation. Using our results, together with scaling estimates of the competing viscous, elastic, inertial and capillary timescales that control the dynamics, we construct a dimensionless map or nomogram summarizing the operating space for each instrument. PMID- 27375825 TI - Parallel temperature-dependent microrheological measurements in a microfluidic chip. AB - Microfluidic stickers are used as a sample environment to measure the microrheology of monoclonal antibody (mAb) protein solutions. A Peltier-based microscope stage is implemented and validated, and is capable of controlling the sample temperature over the range 0.9-40 degrees C. The design accounts for heat transfer to and from the objective, controls the sample environment humidity to mitigate condensation, and provides adequate damping to reduce vibration from the cooling system. A concentrated sucrose solution is used as a standard sample to provide an in situ temperature measurement by the Stokes-Einstein-Sutherland relation. By combining microfluidic stickers and microrheology, 72 temperature concentration viscosity measurements of mAb solutions can be made in 1 day, a significant increase in throughput over conventional rheometry. PMID- 27375826 TI - AC electrified jets in a flow-focusing device: Jet length scaling. AB - We use a microfluidic flow-focusing device with integrated electrodes for controlling the production of water-in-oil drops. In a previous work, we reported that very long jets can be formed upon application of AC fields. We now study in detail the appearance of the long jets as a function of the electrical parameters, i.e., water conductivity, signal frequency, and voltage amplitude. For intermediate frequencies, we find a threshold voltage above which the jet length rapidly increases. Interestingly, this abrupt transition vanishes for high frequencies of the signal and the jet length grows smoothly with voltage. For frequencies below a threshold value, we previously reported a transition from a well-behaved uniform jet to highly unstable liquid structures in which axisymmetry is lost rather abruptly. These liquid filaments eventually break into droplets of different sizes. In this work, we characterize this transition with a diagram as a function of voltage and liquid conductivity. The electrical response of the long jets was studied via a distributed element circuit model. The model allows us to estimate the electric potential at the tip of the jet revealing that, for any combination of the electrical parameters, the breakup of the jet occurs at a critical value of this potential. We show that this voltage is around 550 V for our device geometry and choice of flow rates. PMID- 27375827 TI - Microfluidic rheology of active particle suspensions: Kinetic theory. AB - We analyze the effective rheology of a dilute suspension of self-propelled slender particles confined between two infinite parallel plates and subject to a pressure-driven flow. We use a continuum kinetic model to describe the configuration of the particles in the system, in which the disturbance flows induced by the swimmers are taken into account, and use it to calculate estimates of the suspension viscosity for a range of channel widths and flow strengths typical of microfluidic experiments. Our results are in agreement with previous bulk models, and in particular, demonstrate that the effect of activity is strongest at low flow rates, where pushers tend to decrease the suspension viscosity whereas pullers enhance it. In stronger flows, dissipative stresses overcome the effects of activity leading to increased viscosities followed by shear-thinning. The effects of confinement and number density are also analyzed, and our results confirm the apparent transition to superfluidity reported in recent experiments on pusher suspensions at intermediate densities. We also derive an approximate analytical expression for the effective viscosity in the limit of weak flows and wide channels, and demonstrate good agreement between theory and numerical calculations. PMID- 27375828 TI - Sedentary Behavior and Cardiovascular Risk in Older Adults: a Scoping Review. AB - Sedentary behavior is an emerging risk factor for cardiovascular disease (CVD) and may be particularly relevant to the cardiovascular health of older adults. This scoping review describes the existing literature examining the prevalence of sedentary time in older adults with CVD and the association of sedentary behavior with cardiovascular risk in older adults. We found that older adults with CVD spend >75 % of their waking day sedentary, and that sedentary time is higher among older adults with CVD than among older adults without CVD. High sedentary behavior is consistently associated with worse cardiac lipid profiles and increased cardiac risk scores in older adults; the associations of sedentary behavior with blood pressure, CVD incidence, and CVD-related mortality among older adults are less clear. Future research with larger sample sizes using validated methods to measure sedentary behavior are needed to clarify the association between sedentary behavior and cardiovascular outcomes in older adults. PMID- 27375829 TI - Flexible Bayesian Human Fecundity Models. AB - Human fecundity is an issue of considerable interest for both epidemiological and clinical audiences, and is dependent upon a couple's biologic capacity for reproduction coupled with behaviors that place a couple at risk for pregnancy. Bayesian hierarchical models have been proposed to better model the conception probabilities by accounting for the acts of intercourse around the day of ovulation, i.e., during the fertile window. These models can be viewed in the framework of a generalized nonlinear model with an exponential link. However, a fixed choice of link function may not always provide the best fit, leading to potentially biased estimates for probability of conception. Motivated by this, we propose a general class of models for fecundity by relaxing the choice of the link function under the generalized nonlinear model framework. We use a sample from the Oxford Conception Study (OCS) to illustrate the utility and fit of this general class of models for estimating human conception. Our findings reinforce the need for attention to be paid to the choice of link function in modeling conception, as it may bias the estimation of conception probabilities. Various properties of the proposed models are examined and a Markov chain Monte Carlo sampling algorithm was developed for implementing the Bayesian computations. The deviance information criterion measure and logarithm of pseudo marginal likelihood are used for guiding the choice of links. The supplemental material section contains technical details of the proof of the theorem stated in the paper, and contains further simulation results and analysis. PMID- 27375830 TI - Secondary reconstruction of vaginal stenosis using a posterior labial perforator based Falandry flap. AB - The aim of vaginoplasty should be the creation without excessive morbidity of a neovagina that will be satisfying in appearance, function and feeling. The multitude of methods described in the literature indicates the fact that an ideal approach has not yet been found. In this paper the authors describe the technique for repairing vaginal stenosis by interposing between the vaginal walls, a skin flap pedicled removed using the Falandry technique at a high lip. We achieved a satisfactory result. PMID- 27375831 TI - A case of Kartagener syndrome with rhinolalia clausa. AB - Kartagener syndrome is an autosomal recessive genetic ciliary disorder comprising of a classic triad of sinusitis, situs inversus and bronchiectasis. It's the one of primary ciliary dyskinesia disorders with manifestations present from childhood. Most patients of PCD have situs inversus. We present a case of 18 year old women with recurrent lower and upper respiratory tracts infections, and rhinolalia clausa. PMID- 27375832 TI - Unmasking sarcoidosis following surgery for Cushing disease. AB - We present a patient with Cushing disease apparently suppressing sarcoidosis, which was unmasked following surgical resection of a pituitary adrenocorticotropin (ACTH)-producing microadenoma. Case report and a short review of the literature published in this area. A 46-year-old Caucasian woman presented with symptoms of hypercortisolism such as progressive weight gain, Cushingoid appearance, proximal myopathy, easy bruising, and amenorrhea. Blood testing including inferior petrosal sinus sampling uncovered an ACTH-producing microadenoma in the right aspect of the anterior pituitary gland for which the patient underwent transphenoidal resection. Maintenance corticosteroid therapy was implemented, and the signs and symptoms of Cushing disease began to resolve. Three months after surgery, multiple erythematous painful nodules developed on the patient's arms. Erythema nodosum (EN) was diagnosed clinically and a suspicion of underlying sarcoidosis was substantiated by lung imaging and elevated plasma interleukin (IL)-2 receptor. One month later, the lesions spontaneously resolved without therapy other than maintenance glucocorticoid replacement. Physicians should be aware that patients undergoing successful treatment of Cushing syndrome may have a flare-up or emergence of a corticosteroid-responsive disease. PMID- 27375833 TI - The Role of Imaging in Aortic Valve Disease. AB - PURPOSE OF REVIEW: Aortic valve disease is the most common form of heart valve disease in developed countries. Imaging remains central to the diagnosis and risk stratification of patients with both aortic stenosis and regurgitation and has traditionally been performed with echocardiography. Indeed, echocardiography remains the cornerstone of aortic valve imaging as it is cheap, widely available and provides critical information concerning valve hemodynamics and ventricular function. RECENT FINDINGS: Whilst diagnostic in the vast majority of patients, echocardiography has certain limitations including operator variability, potential for measurement errors and internal inconsistencies in severity grading. In particular, low-gradient severe aortic stenosis is common and challenging to diagnose. Aortic valve imaging may therefore be improved with alternative and complimentary multimodality approaches. SUMMARY: This review investigates established and novel techniques for imaging both the aortic valve and the myocardial remodelling response including echocardiography, computed tomography, cardiovascular magnetic resonance and positron emission tomography. Moreover, we examine how the complementary information provided by each modality may be used in both future clinical practice and the research arena. PMID- 27375834 TI - Molecular and Cellular Effects of Hydrogen Peroxide on Human Lung Cancer Cells: Potential Therapeutic Implications. AB - Lung cancer has a very high mortality-to-incidence ratio, representing one of the main causes of cancer mortality worldwide. Therefore, new treatment strategies are urgently needed. Several diseases including lung cancer have been associated with the action of reactive oxygen species (ROS) from which hydrogen peroxide (H2O2) is one of the most studied. Despite the fact that H2O2 may have opposite effects on cell proliferation depending on the concentration and cell type, it triggers several antiproliferative responses. H2O2 produces both nuclear and mitochondrial DNA lesions, increases the expression of cell adhesion molecules, and increases p53 activity and other transcription factors orchestrating cancer cell death. In addition, H2O2 facilitates the endocytosis of oligonucleotides, affects membrane proteins, induces calcium release, and decreases cancer cell migration and invasion. Furthermore, the MAPK pathway and the expression of genes related to inflammation including interleukins, TNF-alpha, and NF-kappaB are also affected by H2O2. Herein, we will summarize the main effects of hydrogen peroxide on human lung cancer leading to suggesting it as a potential therapeutic tool to fight this disease. Because of the multimechanistic nature of this molecule, novel therapeutic approaches for lung cancer based on the use of H2O2 may help to decrease the mortality from this malignancy. PMID- 27375835 TI - Lipoxin A4 Preconditioning Attenuates Intestinal Ischemia Reperfusion Injury through Keap1/Nrf2 Pathway in a Lipoxin A4 Receptor Independent Manner. AB - Oxidative stress plays a critical role in the pathogenesis of intestinal ischemia reperfusion (IIR) injury. Enhancement in endogenous Lipoxin A4 (LXA4), a potent antioxidant and mediator, is associated with attenuation of IIR. However, the effects of LXA4 on IIR injury and the potential mechanisms are unknown. In a rat IIR (ischemia 45 minutes and subsequent reperfusion 6 hours) model, IIR caused intestinal injury, evidenced by increased serum diamine oxidase, D-lactic acid, intestinal-type fatty acid-binding protein, and the oxidative stress marker 15 F2t-Isoprostane. LXA4 treatment significantly attenuated IIR injury by reducing mucosal 15-F2t-Isoprostane and elevating endogenous antioxidant superoxide dismutase activity, accompanied with Keap1/Nrf2 pathway activation. Meanwhile, LXA4 receptor antagonist Boc-2 reversed the protective effects of LXA4 on intestinal injury but failed to affect the oxidative stress and the related Nrf2 pathway. Furthermore, Nrf2 antagonist brusatol reversed the antioxidant effects conferred by LXA4 and led to exacerbation of intestinal epithelium cells oxidative stress and apoptosis, finally resulting in a decrease of survival rate of rat. Meanwhile, LXA4 pretreatment upregulated nuclear Nrf2 level and reduced hypoxia/reoxygenation-induced IEC-6 cell damage and Nrf2 siRNA reversed this protective effect of LXA4 in vitro. In conclusion, these findings suggest that LXA4 ameliorates IIR injury by activating Keap1/Nrf2 pathway in a LXA4 receptor independent manner. PMID- 27375836 TI - Ultrasonographic Assessment of the Distal Femoral Cartilage Thickness in Patients with Homozygous Sickle Cell Disease. AB - OBJECTIVE: To compare the distal femoral cartilage thickness of patients with sickle cell disease (SCD) with those of healthy subjects using ultrasonography. METHODS: The study comprised 30 patients with SCD (16 male, 14 female; mean age, 30.1 years) and 30 age- and sex-matched healthy subjects. Demographic features and medications of the patients were recorded. With the knees held in maximum flexion, the femoral cartilage thickness was measured bilaterally with a 7- to 12 MHz linear probe. Using ultrasonography, 3 midpoint measurements were taken from both knees: lateral femoral condyle (LFC), intercondylar area (ICA), and medial femoral condyle (MFC). RESULTS: Patients with SCD had thinner femoral cartilage thickness values at LFC (P = 0.004), at MFC (P = 0.000), and ICA (P = 0.002) when compared with those of the healthy subjects. Patients with SCD also had lower Hb levels (P = 0.000) levels. Weak positive correlations were determined between Hemoglobin (Hb) levels and ultrasonographic measurements in the SCD group at MFC (r = 0.331, P = 0.010), and ICA (r = 0.289 , P = 0.025 ). Low levels of Hb seem to affect the femoral cartilage thickness. CONCLUSION: These preliminary findings of decreased femoral cartilage thickness in SCD patients should be complemented with future studies. The possibility of early knee joint degeneration and eventual osteoarthritis in SCD should be kept in mind. PMID- 27375837 TI - Development of a Fresh Osteochondral Allograft Program Outside North America. AB - OBJECTIVE: To standardize and to develop a fresh osteochondral allograft protocol of procurement, processing and surgical utilization in Brazil. This study describes the steps recommended to make fresh osteochondral allografts a viable treatment option in a country without previous fresh allograft availability. DESIGN: The process involves regulatory process modification, developing and establishing procurement, and processing and surgical protocols. RESULTS: Legislation: Fresh osteochondral allografts were not feasible in Brazil until 2009 because the law prohibited preservation of fresh grafts at tissue banks. We approved an amendment that made it legal to preserve fresh grafts for 30 days from 2 degrees C to 6 degrees C in tissue banks. Procurement: We changed the protocol of procurement to decrease tissue contamination. All tissues were procured in an operating room. Processing: Processing of the grafts took place within 12 hours of tissue recovery. A serum-free culture media with antibiotics was developed to store the grafts. Surgeries: We have performed 8 fresh osteochondral allografts on 8 knees obtaining grafts from 5 donors. Mean preoperative International Knee Documentation Committee (IKDC) score was 31.99 +/ 13.4, improving to 81.26 +/- 14.7 at an average of 24 months' follow-up. Preoperative Knee Injury and Oseoarthritis Outcome Score (KOOS) score was 46.8 +/ 20.9 and rose to 85.24 +/- 13.9 after 24 months. Mean preoperative Merle D'Aubigne-Postel score was 8.75 +/- 2.25 rising to 16.1 +/- 2.59 at 24 months' follow-up. CONCLUSION: To our knowledge, this is the first report of fresh osteochondral allograft transplantation in South America. We believe that this experience may be of value for physicians in countries that are trying to establish an osteochondral allograft transplant program. PMID- 27375838 TI - Analysis for Prognostic Factors from a Database for the Intra-Articular Hyaluronic Acid (Euflexxa) Treatment for Osteoarthritis of the Knee. AB - INTRODUCTION: Intra-articular hyaluronic acid (IA-HA) injections are a treatment for knee osteoarthritis (OA), although current literature provides mixed results with regard to their efficacy. We will review a randomized controlled trial (RCT) and subsequent extension trial in order to identify factors that are associated with outcomes in patients with knee OA who received IA-HA. METHODS: We used data recorded by the FLEXX trial and extension trial for secondary analysis of potential prognostic factors. Linear regression was used to examine the predictors of outcomes at 6- and 12-month follow-up visits. RESULTS: Sixty percent of all patients presented with a Kellgren Lawrence (K-L) grade 3. Patients with high baseline outcome scores and a K-L grade 3 demonstrated less response than individuals within an earlier stage of knee OA, although results for both K-L grade 2 and K-L grade 3 patients still showed benefit. Those with more severe radiographic change K-L grade 3 often had a better response with the second series of IA-HA injections. Significantly greater positive response in all outcomes was demonstrated for the patient subgroup classified as K-L grade 2, when compared with K-L grade 3 patients. CONCLUSIONS: The results demonstrate that IA-HA for knee OA was of greater benefit in those with less severe radiographic changes. However, those with more severe radiographic change often had a better response with the second course of IA-HA. Similar analyses are required in order to determine if these results are unique to Euflexxa, or if these results are consistent with other available IA-HA agents. PMID- 27375839 TI - The 50 Most Cited Articles in Orthopedic Cartilage Surgery. AB - OBJECTIVE: To determine the 50 most cited articles in orthopedic cartilage surgery and their characteristics. DESIGN: A systematic review of the Science Citation Index Expanded was performed for articles related to cartilage surgery published in the 66 journals under the category "Orthopedics." The 50 most cited articles were determined, and the following characteristics were analyzed for each article: authors, journal and year of publication, number of citations, geographic origin, article type (basic science or clinical), article subtype by study design, and level of evidence. Citation density (total number of citations/years since publication) was also computed. RESULTS: The 50 most cited articles ranged from 989 to 172 citations, with citation density ranging from 71.5 to 4.1. The publication years spanned from 1968 to 2008, with the 2000s accounting for half (25) of the articles and the highest mean citation density (14.6). The 50 most cited articles were published in 11 journals. The majority of the articles (29) were clinical, with level IV representing the most common level of evidence (10). The remaining basic science articles were most commonly animal in vivo studies (14). Stronger level of evidence was correlated with overall number of citations (P = 0.044), citation density (P < 0.001), and year of publication (P = 0.003). CONCLUSIONS: Articles with stronger levels of evidence are more highly cited, with an increasing trend as evidence-based practice has been emphasized. This article list provides clinicians, researchers, and trainees with a group of "citation classics" in orthopedic cartilage surgery. PMID- 27375840 TI - In Vivo Evaluation of the Potential of High-Frequency Ultrasound for Arthroscopic Examination of the Shoulder Joint. AB - OBJECTIVE: Accurate arthroscopic evaluation of cartilage lesions could significantly improve the outcome of repair surgery. In this study, we investigated for the first time the potential of intra-articular ultrasound as an arthroscopic tool for grading cartilage defects in the human shoulder joint in vivo and compared the outcome to results from arthroscopic evaluation and magnetic resonance imaging findings. DESIGN: A total of 26 sites from 9 patients undergoing routine shoulder arthroscopy were quantitatively evaluated with a clinical intravascular (40MHz) ultrasound imaging system, using the regular arthroscopy portals. Reflection coefficient (R), integrated reflection coefficient (IRC), apparent integrated backscattering (AIB), and ultrasound roughness index (URI) were calculated, and high-resolution ultrasound images were obtained per site. Each site was visually graded according to the International Cartilage Repair Society (ICRS) system. "Ultrasound scores" corresponding to the ICRS system were determined from the ultrasound images. Magnetic resonance imaging was conducted and cartilage integrity at each site was classified into 5 grades (0 = normal, 4 = severely abnormal) by a radiologist. RESULTS: R and IRC were lower at sites with damaged cartilage surface (P = 0.033 and P = 0.043, respectively) and correlated with arthroscopic ICRS grades (r s = -0.444, P = 0.023 and r s = -0.426, P = 0.03, respectively). Arthroscopic ICRS grades and ultrasound scores were significantly correlated (rs = 0.472, P = 0.015), but no significant correlation was found between magnetic resonance imaging data and other parameters. CONCLUSION: The results suggest that ultrasound arthroscopy could facilitate quantitative clinical appraisal of articular cartilage integrity in the shoulder joint and provide information on cartilage lesion depth and severity for quantitative diagnostics in surgery. PMID- 27375841 TI - Superficial Zone Extracellular Matrix Extracts Enhance Boundary Lubrication of Self-Assembled Articular Cartilage. AB - OBJECTIVE: Previous work has shown that increasing the production of boundary lubricant, superficial zone protein (SZP), did not reduce the friction coefficient of self-assembled articular cartilage constructs and was possibly due to poor retention of the lubricant. The aim of this investigation was to reduce the friction coefficient of self-assembled articular cartilage constructs through enhancing SZP retention by the exogenous addition of extracellular matrix (ECM) extracted from the superficial zone of native articular cartilage. DESIGN: Superficial zone cartilage was shaved from juvenile bovine femoral condyles using a dermatome, minced finely with razor blades, extracted with 4 M guanidine hydrochloride, buffer exchanged with culture medium, and added directly to the culture medium of self-assembled articular cartilage constructs at low (10 ug/mL) and high (100 ug/mL) concentrations for 4 weeks. Biochemical and biomechanical properties were determined at the conclusion of 4 weeks culture. RESULTS: ECM treatment increased compressive and tensile stiffness of self-assembled articular cartilage constructs and decreased the friction coefficient. Glycosaminoglycan content decreased and collagen content increased significantly in self-assembled constructs by the ECM treatment. CONCLUSIONS: Friction coefficients of self assembled articular cartilage constructs were reduced by adding extracted superficial zone ECM into the culture medium of self-assembled articular cartilage constructs. PMID- 27375842 TI - A Novel Cross-Linked Hyaluronic Acid Porous Scaffold for Cartilage Repair: An In Vitro Study With Osteoarthritic Chondrocytes. AB - PURPOSE: An important feature of biomaterials used in cartilage regeneration is their influence on the establishment and stabilization of a chondrocytic phenotype of embedded cells. The purpose of this study was to examine the effects of a porous 3-dimensional scaffold made of cross-linked hyaluronic acid on the expression and synthesis performance of human articular chondrocytes. MATERIALS AND METHODS: Osteoarthritic chondrocytes from 5 patients with a mean age of 74 years were passaged twice and cultured within the cross-linked hyaluronic acid scaffolds for 2 weeks. Analyses were performed at 3 different time points. For estimation of cell content within the scaffold, DNA-content (CyQuant cell proliferation assay) was determined. The expression of chondrocyte-specific genes by embedded cells as well as the total amount of sulfated glycosaminoglycans produced during the culture period was analyzed in order to characterize the synthesis performance and differentiation status of the cells. RESULTS: Cells showed a homogenous distribution within the scaffold. DNA quantification revealed a reduction of the cell number. This might be attributed to loss of cells from the scaffold during media exchange connected with a stop in cell proliferation. Indeed, the expression of cartilage-specific genes and the production of sulfated glycosaminoglycans were increased and the differentiation index was clearly improved. CONCLUSIONS: These results suggest that the attachment of osteoarthritic P2 chondrocytes to the investigated material enhanced the chondrogenic phenotype as well as promoted the retention. PMID- 27375843 TI - Mandibular Cartilage Collagen Network Nanostructure: Insights for Regeneration. AB - BACKGROUND: Mandibular condyle cartilage (MCC) has a unique structure among articular cartilages; however, little is known about its nanoscale collagen network architecture, hampering design of regeneration therapies and rigorous evaluation of regeneration experiment outcomes in preclinical research. Helium ion microscopy is a novel technology with a long depth of field that is uniquely suited to imaging open 3D collagen networks at multiple scales without obscuring conductive coatings. OBJECTIVE: The objective of this research was to image, at the micro- and nanoscales, the depth-dependent MCC collagen network architecture. DESIGN: MCC was collected from New Zealand white rabbits. Images of MCC zones were acquired using helium ion, transmission electron, and light microscopy. Network fibril and canal diameters were measured. RESULTS: For the first time, the MCC was visualized as a 3D collagen fibril structure at the nanoscale, the length scale of network assembly. Fibril diameters ranged from 7 to 110 nm and varied by zone. The articular surface was composed of a fine mesh that was woven through thin layers of larger fibrils. The fibrous zone was composed of approximately orthogonal lamellae of aligned fibrils. Fibrocyte processes surrounded collagen bundles forming extracellular compartments. The proliferative, mature, and hypertrophic zones were composed of a branched network that was progressively remodeled to accommodate chondrocyte hypertrophy. Osteoid fibrils were woven around osteoblast cytoplasmic processes to create numerous canals similar in size to canaliculi of mature bone. CONCLUSION: This multiscale investigation advances our foundational understanding of the complex, layered 3D architecture of the MCC collagen network. PMID- 27375845 TI - Potential Application of Novel DNA Editing Techniques in Translational Neuroscience. PMID- 27375844 TI - Repopulating Decellularized Kidney Scaffolds: An Avenue for Ex Vivo Organ Generation. AB - Recent research has shown that fully developed organs can be decellularized, resulting in a complex scaffold and extracellular matrix (ECM) network capable of being populated with other cells. This work has resulted in a growing field in bioengineering focused on the isolation, characterization, and modification of organ derived acellular scaffolds and their potential to sustain and interact with new cell populations, a process termed reseeding. In this review, we cover contemporary advancements in the bioengineering of kidney scaffolds including novel work showing that reseeded donor scaffolds can be transplanted and can function in recipients using animal models. Several major areas of the field are taken into consideration, including the decellularization process, characterization of acellular and reseeded scaffolds, culture conditions, and cell sources. Finally, we discuss future avenues based on the advent of 3D bioprinting and recent developments in kidney organoid cultures as well as animal models of renal genesis. The ongoing mergers and collaborations between these fields hold the potential to produce functional kidneys that can be generated ex vivo and utilized for kidney transplantations in patients suffering with renal disease. PMID- 27375846 TI - Erratum to: Sex differences in the association between infant markers and later autistic traits. PMID- 27366318 TI - Active learning in the lecture theatre using 3D printed objects. AB - The ability to conceptualize 3D shapes is central to understanding biological processes. The concept that the structure of a biological molecule leads to function is a core principle of the biochemical field. Visualisation of biological molecules often involves vocal explanations or the use of two dimensional slides and video presentations. A deeper understanding of these molecules can however be obtained by the handling of objects. 3D printed biological molecules can be used as active learning tools to stimulate engagement in large group lectures. These models can be used to build upon initial core knowledge which can be delivered in either a flipped form or a more didactic manner. Within the teaching session the students are able to learn by handling, rotating and viewing the objects to gain an appreciation, for example, of an enzyme's active site or the difference between the major and minor groove of DNA. Models and other artefacts can be handled in small groups within a lecture theatre and act as a focal point to generate conversation. Through the approach presented here core knowledge is first established and then supplemented with high level problem solving through a "Think-Pair-Share" cooperative learning strategy. The teaching delivery was adjusted based around experiential learning activities by moving the object from mental cognition and into the physical environment. This approach led to students being able to better visualise biological molecules and a positive engagement in the lecture. The use of objects in teaching allows the lecturer to create interactive sessions that both challenge and enable the student. PMID- 27375848 TI - Treatment for substance use disorders: the Belgian Treatment Demand Indicator registration protocol. AB - BACKGROUND: Registration of patients with substance use disorders is of key importance to get insights and to study trends in patients characteristics and substance use patterns. The Treatment Demand Indicator (TDI) is gathering this information at European level since 2000. In Belgium, this registration started at national level in 2011 and an increasing number of facilities of different types are participating in this data collection since then. METHODS/DESIGN: This surveillance register collects information on every treatment episode started by patients for their substance use disorder. Information is collected on socio demographic characteristics of the patient, treatment history and substance use patterns. Patients are identified uniquely using their national identification number in order identify multiple episodes followed by a same person. A large range of treatment facilities have the possibility to participate in this registration to allow a wide coverage of the population. DISCUSSION: The objective of the paper is to facilitate the use of data by authorities or researchers by correctly describing all aspects of the indicator. The case definition, the variables collected and the way data should be reported are of key importance to use and interpret the data correctly. An overview of the data registered in 2014 gives also an idea of the content of the database. The article also pictures the strengths and limitations of the register and foresees some future improvements. PMID- 27375849 TI - Landscape-level movement patterns by lions in western Serengeti: comparing the influence of inter-specific competitors, habitat attributes and prey availability. AB - BACKGROUND: Where apex predators move on the landscape influences ecosystem structure and function and is therefore key to effective landscape-level management and species-specific conservation. However the factors underlying predator distribution patterns within functional ecosystems are poorly understood. Predator movement should be sensitive to the spatial patterns of inter-specific competitors, spatial variation in prey density, and landscape attributes that increase individual prey vulnerability. We investigated the relative role of these fundamental factors on seasonal resource utilization by a globally endangered apex carnivore, the African lion (Panthera leo) in Tanzania's Serengeti National Park. Lion space use was represented by novel landscape-level, modified utilization distributions (termed "localized density distributions") created from telemetry relocations of individual lions from multiple neighbouring prides. Spatial patterns of inter-specific competitors were similarly determined from telemetry re-locations of spotted hyenas (Crocuta crocuta), this system's primary competitor for lions; prey distribution was derived from 18 months of detailed census data; and remote sensing data was used to represent relevant habitat attributes. RESULTS: Lion space use was consistently influenced by landscape attributes that increase individual prey vulnerability to predation. Wet season activity, when available prey were scarce, was concentrated near embankments, which provide ambush opportunities, and dry season activity, when available prey were abundant, near remaining water sources where prey occurrence is predictable. Lion space use patterns were positively associated with areas of high prey biomass, but only in the prey abundant dry season. Finally, at the broad scale of this analysis, lion and hyena space use was positively correlated in the comparatively prey-rich dry season and unrelated in the wet season, suggesting lion movement was unconstrained by the spatial patterns of their main inter-specific competitors. CONCLUSIONS: The availability of potential prey and vulnerability of that prey to predation both motivate lion movement decisions, with their relative importance apparently mediated by overall prey abundance. With practical and theoretical implications, these results suggest that while top carnivores are consistently cognizant of how landscape features influence individual prey vulnerability, they also adopt a flexible approach to range use by adjusting spatial behaviour according to fluctuations in local prey abundance. PMID- 27375850 TI - Diagnostic predictive value of platelet indices for discriminating hypo productive versus immune thrombocytopenia purpura in patients attending a tertiary care teaching hospital in Addis Ababa, Ethiopia. AB - BACKGROUND: Bone marrow examination may be required to discriminate causes of thrombocytopenia as hypoproductive or hyperdestructive. However, this procedure is invasive and time consuming. This study assessed the diagnostic value of Mean Platelet Volume (MPV), Platelet Distribution Width (PDW) and Platelet Large Cell Ratio (P-LCR) in discriminating causes of thrombocytopenia as hypoproductive or hyperdestructive (Immune thrombocytopenia purpura). METHOD: A prospective cross sectional study was conducted on 83 thrombocytopenic patients (Plt < 150 * 10(9)/L). From these, 50 patients had hypoproductive and the rest 33 Immune Thrombocytopenia Purpura (ITP). Age and sex matched 42 healthy controls were included as a comparative group. Hematological analysis was carried out using Sysmex XT 2000i 5 part diff analyzer. SPSS Version16 was used for data analysis. A two by two table and receiver operating characteristic (ROC) curve was used to calculate sensitivity, specificity, positive and negative predictive values, for a given platelet indices (MPV, PDW and P-LCR). Student t test and Mann Whitney U test were used to compare means and medians, respectively. Correlation test was used to determine associations between continuous variables. RESULTS: All Platelet indices were significantly higher in ITP patients (n = 33) than in hypoproductive thrombocytopenic patients (n = 50) (p < 0.0001). In particular MPV and P-LCR have larger area under ROC curve (0.876 and 0.816, respectively), indicating a better predictive capacity, sensitivity and specificity in discriminating the two causes of thrombocytopenia. The indices were still significantly higher in ITP patients compared to 42 healthy controls (p < 0.0001). A significant negative correlation was observed between platelet count and platelet indices in ITP patients, (p < 0.001). CONCLUSION: MPV, PDW and P-LCR help in predicting thrombocytopenic patients as having ITP or hypoproductive thrombocytopenia. If these indices are used in line with other laboratory and clinical information, they may help in delaying/ avoiding unnecessary bone marrow aspiration in ITP patients or supplement a request for bone morrow aspiration or biopsy in hypoproductive thrombocytopenic patients. PMID- 27375851 TI - Perceptions of pediatric nephrologists regarding timing of dialysis initiation in children in Canada. AB - BACKGROUND: Significant practice variation exists in Canada with respect to timing of dialysis initiation in children. In the absence of evidence to guide practice, physicians' perceptions may significantly influence decision-making. OBJECTIVE: The objectives of this study are to (1) evaluate Canadian pediatric nephrologists' perceptions regarding dialysis initiation in children with chronic kidney disease (CKD) and (2) determine the factors guiding practice that may contribute to practice variation across Canada. DESIGN: This study was a cross sectional online survey. SETTING: This study was done in academic pediatric nephrology centers in Canada. PARTICIPANTS: The participants of this study are pediatric nephrologists. MEASUREMENTS AND METHODS: An anonymous web-based survey was administered to pediatric nephrologists in Canada to evaluate perspectives and practice patterns regarding timing of dialysis initiation. We also explored the importance of estimated glomerular filtration rate (eGFR) vs. symptoms and the role of patient and provider factors influencing decisions. RESULTS: Thirty five nephrologists (59 %) completed the survey. Most respondents care for advanced CKD patients in a multidisciplinary clinic (86 %) and no centers have a formal policy on timing of dialysis initiation. Seventy-five percent of centers follow <20 stage 4-5 CKD patients, and 9 % follow >30 patients. Discussions about dialysis initiation are generally informal (75 %) and the decision to start is made by the nephrologist (37 %) or a team (57 %). Fifty percent agreed GFR was important when deciding when to initiate dialysis, 41 % were neutral, and 9 % disagreed. Variability exists in the threshold that nephrologists considered early (vs. late) dialysis initiation: >20 (21 %), >15 (38 %), >12 (26 %), and >10 ml/min/1.73 m(2) (12 %). Practitioners however typically start dialysis in asymptomatic patients at eGFRs of 7-9 (9 %), 10-11 (41 %), 12-14 (38 %), and 15 19 (6 %) ml/min/1.73 m(2). Patient factors important in the decision to start dialysis for >90 % of nephrologists were fatigue, >10 % weight loss, nausea, increasing missed school, and awaiting a pre-emptive transplant. Age was only a factor for 56 %. LIMITATIONS: This study has a 59 % response rate. CONCLUSIONS: Variability exists in Canada regarding the importance and threshold of eGFR guiding the decision as to when to start dialysis in children, whereas patient symptoms are almost universally important to pediatric nephrologists' decision making. Additional studies evaluating outcomes of children starting dialysis earlier vs. later are needed to standardize decision-making and care for children with kidney failure. PMID- 27375852 TI - Motherside care of the term neonate at birth. AB - The rationale for keeping the mother and her newborn together even when neonatal resuscitation is required is presented. The development of a customised mobile resuscitation trolley is detailed explaining how the resuscitation team can be provided with all the facilities of a standard resuscitation trolley to resuscitate the neonate at the mother's side with an intact cord. Alternative low tech solutions which may be appropriate in low resource setting and with a low risk population are also described. PMID- 27375853 TI - Effect of supplementation of feed with Flaxseed (Linumusitatisimum) oil on libido and semen quality of Nilli-Ravi buffalo bulls. AB - BACKGROUND: The current study was designed to investigate the effect of supplementation of Flaxseed (Linumusitatisimum) oil on libido and semen quality of Nilli-Ravi buffalo bulls. METHODS: In this study, 12 adult healthy bulls kept at the Semen Production Unit, Qadirabad district Sahiwal, were used. These bulls were divided into three equal groups, A, B and C. Group A was kept as control, while in groups B and C supplementation of feed was provided by using flaxseed oil @125 ml/day and 250 ml/day,respectively for 12 weeks. Two ejaculates per animal were collected at 0 day then 5th, 6th, 7th, 8th, 9th, 10th, 11th and 12th week of treatment. In this way a total 216 samples were taken, and each semen sample was evaluated for color, volume, mass activity, percent motility, sperm cell concentration per ml, percentage of live sperm, and plasma membrane integrity. Libido of bulls was also evaluated before every collection. RESULTS: Analysis of data revealed that these parameters were significantly (P < 0.01) increased in flax oil treated animals as compared to control. CONCLUSION: It was concluded from the present study that flax seed oil has beneficial effects on reproductive health of buffalo bull. PMID- 27375854 TI - Machine learning identification of EEG features predicting working memory performance in schizophrenia and healthy adults. AB - BACKGROUND: With millisecond-level resolution, electroencephalographic (EEG) recording provides a sensitive tool to assay neural dynamics of human cognition. However, selection of EEG features used to answer experimental questions is typically determined a priori. The utility of machine learning was investigated as a computational framework for extracting the most relevant features from EEG data empirically. METHODS: Schizophrenia (SZ; n = 40) and healthy community (HC; n = 12) subjects completed a Sternberg Working Memory Task (SWMT) during EEG recording. EEG was analyzed to extract 5 frequency components (theta1, theta2, alpha, beta, gamma) at 4 processing stages (baseline, encoding, retention, retrieval) and 3 scalp sites (frontal-Fz, central-Cz, occipital-Oz) separately for correctly and incorrectly answered trials. The 1-norm support vector machine (SVM) method was used to build EEG classifiers of SWMT trial accuracy (correct vs. incorrect; Model 1) and diagnosis (HC vs. SZ; Model 2). External validity of SVM models was examined in relation to neuropsychological test performance and diagnostic classification using conventional regression-based analyses. RESULTS: SWMT performance was significantly reduced in SZ (p < .001). Model 1 correctly classified trial accuracy at 84 % in HC, and at 74 % when cross-validated in SZ data. Frontal gamma at encoding and central theta at retention provided highest weightings, accounting for 76 % of variance in SWMT scores and 42 % variance in neuropsychological test performance across samples. Model 2 identified frontal theta at baseline and frontal alpha during retrieval as primary classifiers of diagnosis, providing 87 % classification accuracy as a discriminant function. CONCLUSIONS: EEG features derived by SVM are consistent with literature reports of gamma's role in memory encoding, engagement of theta during memory retention, and elevated resting low-frequency activity in schizophrenia. Tests of model performance and cross-validation support the stability and generalizability of results, and utility of SVM as an analytic approach for EEG feature selection. PMID- 27375855 TI - Attenuation of high sucrose diet-induced insulin resistance in ABC transporter deficient white mutant of Drosophila melanogaster. AB - Exposure to high sugar diet (HSD) is an experimental model of insulin resistance (IR) and type 2 diabetes (T2D) in mammals and insects. In Drosophila, HSD-induced IR delays emergence of pupae from larvae and eclosion of imago from pupae. Understanding of mechanisms of IR/T2D is essential for refining T2D prevention and treatment strategies. Dysregulation of tryptophan (Trp)-kynurenine (Kyn) pathway was suggested as one of the mechanisms of IR/T2D development. Rate limiting enzyme of Trp-Kyn pathway in Drosophila is Trp 2,3-dioxygenase (TDO), an evolutionary conserved ortholog of human TDO. We previously reported attenuation of HSD-induced IR in vermilion mutants with inactive TDO. Conversion of Trp to Kyn is regulated not only by TDO activity but by intracellular Trp transport via ATP-binding cassette (ABC) transporter encoded by white gene in Drosophila. In order to evaluate the possible impact of deficient intracellular Trp transport on the inducement of IR by HSD, we compared the effect of HSD on pre-imago development in wild type flies, Canton-Special (C-S), and C-S flies containing white gene, white (C-S). Presence of white gene attenuated (by 50%) HSD-induced delay of pupae emergence from larvae and female and male imago eclosion from pupae. Present study together with our earlier report reveals that both decreased TDO activity (due to vermilion gene mutation) or deficient Trp transport into cell without affecting TDO levels (due to white gene mutation) attenuate HSD induced development of IR in Drosophila model of T2D. Our data provide further support for hypothesis that dysregulation of Trp-Kyn pathway is one of the pathophysiological mechanisms and potential target for early diagnosis, prevention and treatment of IR/T2D. PMID- 27375856 TI - Crystal structures of N-(3-fluoro-benzo-yl)benzene-sulfonamide and N-(3-fluoro benzo-yl)-4-methyl-benzene-sulfonamide. AB - The crystal structures of two N-(aryl-sulfon-yl)aryl-amides, namely N-(3-fluoro benzo-yl)benzene-sulfonamide, C13H10FNO3S, (I), and N-(3-fluoro-benzo-yl)-4 methyl-benzene-sulfonamide, C14H12FNO3S, (II), are described and compared with related structures. The dihedral angle between the benzene rings is 82.73 (10) degrees in (I) compared to 72.60 (12) degrees in (II). In the crystal of (I), the mol-ecules are linked by C-H?O and C-H?pi inter-actions, resulting in a three dimensional grid-like architecture, while C-H?O inter-actions lead to one dimensional ribbons in (II). The crystals of both (I) and (II) feature strong but non-structure-directing N-H?O hydrogen bonds with R 2 (2)(8) ring motifs. The structure of (I) also features pi-pi stacking inter-actions. PMID- 27375857 TI - Crystal structure of bis-(N-tert-butyl-benzamidinium) hexa-chlorido-zirconate(IV) di-chloro-methane disolvate. AB - In the Zr(IV) complex anion of the title complex salt, [(C4H9)HNC(C6H5)NH2]2[ZrCl6].2CH2Cl2, the Zr(IV) cation, located on an inversion centre, is coordinated by six Cl(-) anions in a distorted octa-hedral geometry with Zr-Cl distances in the range 2.433 (2)-2.4687 (19) A; in the amidinium cation, the dihedral angle between the aromatic ring and [NCN] plane is 43.3 (4) degrees . In the crystal, the amidinium cations and [ZrCl6](2-) anions are linked by N-H?Cl hydrogen bonds, forming a two-dimensional network extending along the b axis; two di-chloro-methane solvent mol-ecules are linked by a pair of weak C H?Cl hydrogen bonds, forming a centrosymmetric [CHCl]2 six-membered ring. PMID- 27375858 TI - Crystal structure of 4-carbamoylpyridinium chloride. AB - The hydro-chloride salt of isonicotinamide, C6H7N2O(+).Cl(-), has been synthesized from a dilute solution of hydro-chloric acid in aceto-nitrile. The compound displays monoclinic symmetry (space group C2/c) at 150 K, similar to the related hydro-chloride salt of nicotinamide. The asymmetric unit contains one protonated isonicotinamide mol-ecule and a chloride anion. An array of hydrogen bonding inter-actions, including a peculiar bifurcated pyridinium-chloride inter action, results in linear chains running almost perpendicularly in the [150] and [1-50] directions within the structure. A description of the hydrogen-bonding network and comparison with similar compounds are presented. PMID- 27375860 TI - Crystal structure of bis-[(acetato-kappaO)(imidazolidine-2-thione-kappaS)bis-(tri phenyl-phosphane-kappaP)silver(I)] di-MU-imidazol-idine-2-thione-kappa(4) S:S-bis [(imidazol-id-ine-2-thione-kappaS)bis-(tri-phenyl-phosphane-kappaP)silver(I)] di acetate aceto-nitrile disolvate tetra-hydrate. AB - In the title compound, [Ag2(C3H6N2S)4(C18H15P)2](C2H3O2)2.[Ag(C2H3O2)(C3H6N2S)(C18H15P)2]2.2C2H3N.4H2O, the Ag(I) ion in the mononuclear neutral complex exhibits a distorted tetra hedral environment with coordination by two P atoms from tri-phenyl-phosphane (PPh3) ligands, one S atom of an imidazolidine-2-thione (etu) ligand and one O atom of an acetate anion. The binuclear cationic complex comprises two inversion related [Ag(C3H6N2S)2(C18H15P)] units with Ag(I) ions bridged by two S atoms from etu ligands forming a four-membered Ag-S-Ag-S ring. Each Ag(I) ion is coordinated by a P atom of a PPh3 ligand, two S atoms of bridging etu ligands and the terminal S atom of an etu ligand in a distorted tetra-hedral environment. In the crystal, the mononuclear complex is linked to lattice water mol-ecules through O H?O and N-H?O hydrogen bonds, forming a chain along [100]. In addition, the binuclear complex mol-ecules are connected to acetate anions and lattice water mol-ecules via O-H?O, N-H?O and O-H?S hydrogen bonds, also along [100]. PMID- 27375859 TI - Crystal structure of poly[(4-amino-pyridine-kappaN)(N,N-di-methyl-formamide kappaO)(MU3-pyridine-3,5-di-carboxyl-ato-kappa(3) N:O (3):O (5))copper(II)]. AB - The title compound, [Cu(C7H3NO4)(C5H6N2)(C3H7NO] n , is an amino-function-alized chiral metal-organic framework with (10,3)-a topology. It has been constructed via the assembly of the achiral triconnected pyridine-3,5-di-carboxyl-ate (3,5 PDC) building block and a triconnected Cu(II) atom. Each Cu(II) ion is coordinated by two O atoms and one N atom, respectively, of three crystallographically independent 3,5-PDC ligands. The square-pyramidal (CuN2O3) coordination geometry of the Cu(II) ion is completed by an N atom of a terminal 4 amino-pyridine (4-APY) ligand and the O atom of a terminal N,N-di-methyl formamide (DMF) ligand to give a triconnected 'T'-shaped secondary building unit, which becomes trigonal in the resulting (10,3)-a topology. In the three dimensional structure, weak N-H?O hydrogen bonds are observed in which the donor N-H groups are provided by the 4-APY ligands and the acceptor O atoms are provided by the non-coordinating carboxylate O atoms of the 3,5-PDC ligands. PMID- 27375861 TI - Crystal structure of octa-kis-(N,N-di-methyl-formamide-kappaO)europium(III) tetra cosa-MU2-oxido-dodeca-oxido-MU12-phosphato-dodeca-molybdate(VI). AB - In the title salt, [Eu(C3H7NO)8][PMo12O40], the asymmetric unit comprises one alpha-Keggin-type [PMo12O40](3-) polyoxidometalate anion and one distorted dodeca hedral [Eu(C3H7NO)8](3+) complex cation. In the crystal, the isolated polyoxidometalate anions are packed into hexa-gonally arranged rows extending parallel to [001]. The complex cations are situated between the rows and are linked to the neighbouring anions through weak C-H?O hydrogen-bonding inter actions, leading to the formation of a three-dimensional network structure. PMID- 27375862 TI - Crystal structure of (E)-9-(4-nitro-benzyl-idene)-8,9-di-hydro-pyrido[2,3 d]pyrrolo-[1,2-a]pyrimidin-5(7H)-one. AB - The title compound, C17H12N4O3, a pyrido-pyrrolo-pyrimidine derivative, is almost planar. The nitro-benzene ring is inclined to the mean plane of the 8,9-di-hydro pyrido[2,3-d]pyrrolo-[1,2-a]pyrimidin-5(7H)-one moiety (r.m.s. deviation = 0.023 A) by 6.8 (1) degrees . In the crystal, mol-ecules are linked via C-H?O and C-H?N hydrogen bonds, forming layers parallel to (101). PMID- 27375863 TI - Crystal structure of trans-diammine(1,4,8,11-tetra-aza-cyclo-tetra-decane kappa(4) N)chromium(III) tetra-chlorido-zincate chloride monohydrate from synchrotron data. AB - The asymmetric unit of the title complex salt, [Cr(C10H24N4)(NH3)2][ZnCl4]Cl.H2O, is comprised of four halves of the Cr(III) complex cations (the counterparts being generated by application of inversion symmetry), two tetra-chlorido-zincate anions, two chloride anions and two water mol-ecules. Each Cr(III) ion is coordinated by the four N atoms of the cyclam (1,4,8,11-tetra-aza-cyclo-tetra deca-ne) ligand in the equatorial plane and by two N atoms of ammine ligands in axial positions, displaying an overall distorted octa-hedral coordination environment. The Cr-N(cyclam) bond lengths range from 2.0501 (15) to 2.0615 (15) A, while the Cr-(NH3) bond lengths range from 2.0976 (13) to 2.1062 (13) A. The macrocyclic cyclam moieties adopt the trans-III conformation with six- and five membered chelate rings in chair and gauche conformations. The [ZnCl4](2-) anions have a slightly distorted tetra-hedral shape. In the crystal, the Cl(-) anions link the complex cations, as well as the solvent water mol-ecules, through N-H?Cl and O-H?Cl hydrogen-bonding inter-actions. The supra-molecular set-up also includes N-H?Cl, C-H?Cl, N-H?O and O-H?Cl hydrogen bonding between N-H or C-H groups of cyclam, ammine N-H and water O-H donor groups, and O atoms of the water mol-ecules, Cl(-) anions or Cl atoms of the [ZnCl4](2-) anions as acceptors, leading to a three-dimensional network structure. PMID- 27375864 TI - Crystal structure of a bioactive sesquiterpene isolated from Artemisia reticulata. AB - The title compound, C15H24O2 {systematic name: 1-[6-hy-droxy-7-(propan-2-yl)-4 methyl-idene-2,3,3a,4,5,6,7,7a-octa-hydro-1H-inden-1-yl]ethanone} was iso-la-ted from A. reticulata by column chromatography over silica gel by gradient solvent elution. The mol-ecule comprises a bi-cyclo-[4.3.0]nonane ring bearing acet-oxy, hy-droxy and isopropyl substituents, and an exocyclic double bond on the cyclo hexane ring. In the bicyclic skeleton, the cyclo-hexane ring adopts a chair conformation ring and the cyclo-pentane ring is in an envelope conformation. In the crystal, mol-ecules are linked by O-H?O hydrogen bonds, forming chains along [010]. These chains are cross-linked by C-H?O hydrogen bonds. PMID- 27375865 TI - Crystal structure of a photobiologically active furan-ocoumarin from Artemisia reticulata. AB - The title furan-ocoumarin, C14H12O4 [systematic name: 9-hy-droxy-2-(prop-1-en-2 yl)-2,3-di-hydro-7H-furo[3,2-g]chromen-7-one], crystallizes with two independent mol-ecules (A and B) in the asymmetric unit. The two mol-ecules differ essentially in the orientation of the propenyl group with respect to the mean plane of the furan-ocoumarin moiety; the O-C(H)-C=C torsion angle is 122.2 (7) degrees in mol-ecule A and -10.8 (11) degrees in mol-ecule B. In the crystal, the A and B mol-ecules are linked via O-H?O hydrogen bonds, forming zigzag -A-B-A B- chains propagating along [001]. The chains are reinforced by bifurcated C H?(O,O) hydrogen bonds, forming ribbons which are linked via C-H?pi and pi-pi inter-actions [inter-centroid distance = 3.602 (2) A], forming a three dimensional structure. PMID- 27375866 TI - Crystal structure of (E,E)-2',4'-di-hydroxy-aceto-phenone azine di-methyl formamide disolvate. AB - In the title compound {systematic name: 4,4'-[1,1'-(hydrazinediyl-idene)bis (ethan-1-yl-1-yl-idene)]bis-(benzene-1,3-diol)}, C16H16N2O4.2C3H7NO, the (E,E) 2',4'-di-hydroxy-aceto-phenone azine mol-ecule is centrosymmetric, the mid-point of the N-N bond being located on an inversion centre. All the non-H atoms of the azine mol-ecule are approximately coplanar, the maximum deviation being 0.017 (2) A. An intra-molecular O-H?N hydrogen bond occurs between the azine N atom and the hy-droxy group. In the crystal, azine and di-methyl-formamide solvent mol-ecules are linked by O-H?O hydrogen bonds. PMID- 27375867 TI - Bis{bis-(azido-kappaN)bis-[bis-(pyridin-2-yl-kappaN)amine]cobalt(III)} sulfate dihydrate. AB - The search for new mol-ecular materials with inter-esting magnetic properties, using the pseudohalide azide ion and di-2-pyridyl-amine (dpa, C10H9N3) as a chelating ligand, led to the synthesis and structure determination of the title compound, [Co(N3)2(dpa)2]2SO4.2H2O. The crystal structure comprises discrete [Co(dpa)2(N3)2](+) cations, sulfate anions, as well as H2O solvent mol-ecules. The Co(III) cations display a slightly distorted octa-hedral coordination sphere defined by two N atoms from azide anions and four N atoms from the pyridyl rings of two dpa ligands. In the crystal, extensive C-H?O, N-H?O, and O-H?O inter actions result in supra-molecular sheets that lie parallel to the ab plane. The sheets are further linked through O-H?N inter-actions between the water mol ecules of one sheet and azide anions of another sheet, forming a supra-molecular framework. PMID- 27375868 TI - Comparison of the crystal structures of methyl 4-bromo-2-(meth-oxy-meth oxy)benzoate and 4-bromo-3-(meth-oxy-meth-oxy)benzoic acid. AB - The title compounds, C10H11BrO4, (I), and C9H9BrO4, (II), are derivatives of bromo-hy-droxy-benzoic acids. Compound (II) crystallizes with two independent mol ecules (A and B) in the asymmetric unit. In both (I) and (II), the O-CH2-O-CH3 side chain is not in its fully extended conformation; the O-C-O-C torsion angle is 67.3 (3) degrees in (I), and -65.8 (3) and -74.1 (3) degrees in mol-ecules A and B, respectively, in compound (II). In the crystal of (I), mol-ecules are linked by C-H?O hydrogen bonds, forming C(5) chains along [010]. The chains are linked by short Br?O contacts [3.047 (2) A], forming sheets parallel to the bc plane. The sheets are linked via C-H?pi inter-actions, forming a three dimensional architecture. In the crystal of (II), mol-ecules A and B are linked to form R 2 (2)(8) dimers via two strong O-H?O hydrogen bonds. These dimers are linked into ?A-B?A-B?A-B? [C 2 (2)(15)] chains along [011] by C-H?O hydrogen bonds. The chains are linked by slipped parallel pi-pi inter-actions [inter centroid distances = 3.6787 (18) and 3.8431 (17) A], leading to the formation of slabs parallel to the bc plane. PMID- 27375869 TI - Crystal structures of the two salts 2-methyl-1H-imidazol-3-ium nitrate-2-methyl 1H-imidazole (1/1) and 2-methyl-1H-imidazol-3-ium nitrate. AB - The title salts, C4H7N2 (+).NO3 (-).C4H6N2, (I), and C4H7N2 (+).NO3 (-), (II), were obtained from solutions containing 2-methyl-imidazole and nitric acid in different concentrations. In the crystal structure of salt (I), one of the -NH H atoms of the imidazole ring shows half-occupancy, hence only every second mol ecule is in its cationic form. The nitrate anion in this structure lies on a twofold rotation axis. The neutral 2-methyl-imidazole mol-ecule and the 2-methyl 1H-imidazol-3-ium cation inter-act through N-H?N hydrogen bonds to form [(C4H6N2)?(C4H7N2)(+)] pairs. These pairs are linked with two nitrate anions on both sides through bifurcated N-H?(O,O) hydrogen bonds into chains running parallel to [001]. In the crystal structure of salt (II), the C4H7N2 (+) cation and the NO3 (-) anion are both located on a mirror plane, leading to a statistical disorder of the methyl H atoms. The cations and anions again inter act through bifurcated N-H?(O,O) hydrogen bonds, giving rise to the formation of chains consisting of alternating anions and cations parallel to [100]. PMID- 27375870 TI - Crystal structure of bis-{MU2-3-(pyridin-2-yl)-5-[(1,2,4-triazol-1-yl)meth-yl] 1,2,4-triazolato}bis-[aqua-nitrato-copper(II)] dihydrate. AB - The structure of the dinuclear title complex, [Cu2(C10H8N7)2(NO3)2(H2O)2].2H2O, consists of centrosymmetric dimeric units with a copper-copper separation of 4.0408 (3) A. The Cu(II) ions in the dimer display a distorted octa-hedral coordination geometry and are bridged by two triazole rings, forming an approximately planar Cu2N4 core (r.m.s. deviation = 0.049 A). In the crystal, O H?O, O-H?N and C-H?O hydrogen bonds and pi-pi inter-actions link the mol-ecules into a three-dimensional network. PMID- 27375871 TI - Crystal structure of tetra-kis-[MU2-2-(di-methyl-amino)-ethano-lato-kappa(3) N,O:O]di-MU3-hydroxido-di-thio-cyanato-kappa(2) N-dichromium(III)dilead(II) di thio-cyanate aceto-nitrile monosolvate. AB - The tetra-nuclear complex cation of the title compound, [Cr2Pb2(NCS)2(OH)2(C4H10NO)4](SCN)2.CH3CN, lies on an inversion centre. The main structural feature of the cation is a distorted seco-norcubane Pb2Cr2O6 cage with a central four-membered Cr2O2 ring. The Cr(III) ion is coordinated in a distorted octa-hedron, which involves two N atoms of one bidentate ligand and one thio cyanate anion, two MU2-O atoms of 2-(di-methyl-amino)-ethano-late ligands and two MU3-O atoms of hydroxide ions. The coordination geometry of the Pb(II) ion is a distorted disphenoid, which involves one N atom, two MU2-O atoms and one MU3-O atom. In addition, weak Pb?S inter-actions involving the coordinating and non coordinating thio-cyanate anions are observed. In the crystal, the complex cations are linked through the thio-cyanate anions via the Pb?S inter-actions and O-H?N hydrogen bonds into chains along the c axis. The chains are further linked together via S?S contacts. The contribution of the disordered solvent aceto nitrile mol-ecule was removed with the SQUEEZE [Spek (2015 ?). Acta Cryst. C71, 9 18] procedure in PLATON. The solvent is included in the reported mol-ecular formula, weight and density. PMID- 27375872 TI - A [Cu3(MU3-O)]-pyrazolate metallacycle with terminal nitrate ligands exhibiting point group symmetry 3. AB - The trinuclear triangular cuprate anion of the title compound, tris-[bis-(tri phenyl-phospho-ranyl-idene)ammonium] tris-(MU2-4-chloro-pyrazolato-kappa(2) N:N') MU3-oxido-tris-[(nitrato-kappa(2) O,O')cuprate(II)] nitrate monohydrate, (C36H30P2N)[Cu3(C3H2ClN2)3(NO3)3O]NO3.H2O, has point group symmetry 3., with the MU3-O atom located on the threefold rotation axis. The distorted square-pyramidal coordination sphere of the Cu(II) atom is completed by two N atoms of trans bridging pyrazolate groups and a chelating nitrate anion. The complex anion is slightly bent, with the nitrate and pyrazolate groups occupying positions above and below the Cu3 plane, respectively. In the crystal, weak O-H?O and C-H?O hydrogen bonds, as well as pi-pi inter-actions, are present. PMID- 27375873 TI - Crystal structure of Na4Co7-x Al0.67x (As1-y P y O4)6 (x = 1.60; y = 0.116). AB - The title compound, tetra-sodium hepta-(cobalt/aluminium) hexa (arsenate/phosphate), Na4Co5.40Al1.07(As0.883P0.116O4)6, was prepared by a solid state reaction. It is a new member of the family of isostructural compounds with the general formula A 4 M 7(XO4)6 (A: Na, K; M: Ni, Co; X: P, As) that is most similar to Na4Co5.63Al0.91(AsO4)6. The Co(2+) ions in the title compound are substituted by Al(3+) in a fully occupied octa-hedral site (site symmetry 2/m) and a partially occupied tetra-hedral site (site symmetry 2). A third octa-hedral site is fully occupied by Co(2+) ions only. With regard to the P and As atoms, one site (site symmetry m) is simultaneously occupied by As and P, whereas in the second site there is only arsenic. The alkali cations are, as in the isostructural compounds, distributed over half-occupied crystallographic sites, with a positional disorder of one of them. The proposed structural model is based both on a careful investigation of the crystal data, as well as validation by means of bond-valence-sum (BVS) and charge-distribution (CHARDI) calculations. The correlation between the X-ray refinement and the validation results is discussed. PMID- 27375874 TI - Crystal structure of di-aqua-bis-(N,N-di-ethyl-nicotinamide-kappaN (1))bis-(2,4,6 tri-methyl-benzoato-kappaO (1))cobalt(II). AB - The centrosymmetric mol-ecule in the monomeric title cobalt complex, [Co(C10H11O2)2(C10H14N2O)2(H2O)2], contains two water mol-ecules, two 2,4,6-tri methyl-benzoate (TMB) ligands and two di-ethyl-nicotinamide (DENA) ligands. All ligands coordinate to the Co(II) atom in a monodentate fashion. The four O atoms around the Co(II) atom form a slightly distorted square-planar arrangement, with the distorted octa-hedral coordination sphere completed by two pyridine N atoms of the DENA ligands. The dihedral angle between the planar carboxyl-ate group and the adjacent benzene ring is 84.2 (4) degrees , while the benzene and pyridine rings are oriented at a dihedral angle of 38.87 (10) degrees . The water mol ecules exhibit both intra-molecular (to the non-coordinating carboxyl-ate O atom) and inter-molecular (to the amide carbonyl O atom) O-H?O hydrogen bonds. The latter lead to the formation of layers parallel to (100), enclosing R 4 (4)(32) ring motifs. These layers are further linked via weak C-H?O hydrogen bonds, resulting in a three-dimensional network. One of the two ethyl groups of the DENA ligand is disordered over two sets of sites with an occupancy ratio of 0.490 (13):0.510 (13). PMID- 27375875 TI - Crystal structure of trans-bis-(di-ethano-lamine-kappa(3) O,N,O')manganese(II) bis-(3-amino-benzoate). AB - Reaction of m-amino-benzoic acid (MABA), di-ethano-lamine (DEA) and MnCl2.4H2O led to the formation of the title salt, [Mn(C4H11NO2)2](C7H6NO2)2. In the complex cation, the Mn(2+) ion is located on an inversion centre and is coordinated by two symmetry-related tridentate DEA mol-ecules, leading to the formation of a slightly distorted MnN2O4 octa-hedron. The MABA(-) counter-anions are connected to the complex ion by a pair of rather strong O-H?O hydrogen bonds, yielding a 1:2 supra-molecular aggregate. Much weaker N-H?O hydrogen bonds connect neighbouring aggregates into a three-dimensional network structure. PMID- 27375876 TI - Crystal structure of spinel-type Li0.64Fe2.15Ge0.21O4. AB - Spinel-type Li0.64Fe2.15Ge0.21O4, lithium diiron(III) germanium tetra-oxide, has been formed as a by-product during flux growth of an Li-Fe-Ge pyroxene-type material. In the title compound, lithium is ordered on the octa-hedral B sites, while Ge(4+) orders onto the tetra-hedral A sites, and iron distributes over both the octa-hedral and tetra-hedral sites, and is in the trivalent state as determined from Mossbauer spectroscopy. The oxygen parameter u is 0.2543; thus, the spinel is close to having an ideal cubic closed packing of the O atoms. The title spinel is compared with other Li- and Ge-containing spinels. PMID- 27375877 TI - Redetermination of cytosinium hydrogen maleate-cytosine (1/1) from the original data. AB - The title salt, C4H6N3O(+).C4H3O4 (-).C4H5N3O, has been redetermined from the data published by Benali-Cherif, Falek & Direm [Acta Cryst. (2009), E65, o3058 o3059]. The improvement of the present redetermination consists in the discovery of the splitting of one of the H atoms into two disordered positions, the occupancies of which are equal to 0.55 (2) and 0.45 (2). These H atoms are involved in an N?N hydrogen bond and are shifted towards its centre. The disorder of these H atoms is in agreement with a similar environment of the two independent, but chemically equivalent, cytosinium/cytosine mol-ecules. PMID- 27375878 TI - A redetermination from the original data of the crystal structure of 2-amino-4,6 di-meth-oxy-pyrimidin-1-ium 4-amino-benzoate. AB - The title structure, C6H9.5N3O2 (0.5+).C7H6.5NO2 (0.5-), which might be named schematically as 2-amino-4,6-di-meth-oxy-pyrimidine-(MU2-hydrogen)-4-amino benzoate to indicate a bridging H atom, has been redetermined from the data published by Thanigaimani, Mu-thiah & Lynch [Acta Cryst. (2006), E62, o2976 o2978]. The improvement of the present redetermination consists in a released geometry of the primary amine groups, which were originally assumed to be planar, as well as in a redetermination of the position of the hy-droxy H atom. This H atom, whose parameters were originally constrained, turns out to be situated about the centre of the O?N hydrogen bond in two disordered positions with occupancies of 0.5 each. PMID- 27375879 TI - 2-[(1E)-({[(Benzyl-sulfan-yl)methane-thio-yl]amino}-imino)-meth-yl]-6-meth-oxy phenol: crystal structure and Hirshfeld surface analysis. AB - The title di-thio-carbazate ester, C16H16N2O2S2, comprises two almost planar residues, i.e. the phenyl ring and the remaining 14 non-H atoms (r.m.s. deviation = 0.0410 A). These are orientated perpendicularly, forming a dihedral angle of 82.72 (5) degrees . An intra-molecular hy-droxy-O-H?N(imine) hydrogen bond, leading to an S(6) loop, is noted. An analysis of the geometric parameters is consistent with the mol-ecule existing as the thione tautomer, and the conformation about the C=N bond is E. The thione S and imine H atoms lie to the same side of the mol-ecule, facilitating the formation of inter-molecular N-H?S hydrogen bonds leading to eight-membered {?HNCS}2 synthons in the crystal. These aggregates are connected by phenyl-C-H?O(hy-droxy) inter-actions into a supra molecular layer in the bc plane; these stack with no directional inter-actions between them. An analysis of the Hirshfeld surface confirms the nature of the inter-molecular inter-actions. PMID- 27375880 TI - Crystal structure of 3-(4-hy-droxy-phen-yl)-2-[(E)-2-phenyl-ethen-yl]quinazolin 4(3H)-one. AB - The title compound, C22H16N2O2 {systematic name: 3-(4-hy-droxy-phen-yl)-2-[(E)-2 phenyl-ethen-yl]quinazolin-4(3H)-one}, consists of a substituted 2-[(E)-2-aryl ethen-yl]-3-aryl-quinazolin-4(3H)-one skeleton. The substituents at the ethyl-ene fragment are located in trans positions. The phenyl ring is inclined to the quinazolone ring by 26.44 (19) degrees , while the 4-hy-droxy-phenyl ring is inclined to the quinazolone ring by 81.25 (8) degrees . The phenyl ring and the 4 hy-droxy-phenyl ring are inclined to one another by 78.28 (2) degrees . In the crystal, mol-ecules are connected via O-H?O hydrogen bonds, forming a helix along the a-axis direction. The helices are linked by C-H?pi inter-actions, forming slabs parallel to (001). PMID- 27375881 TI - Crystal structure of the salt bis-(tri-ethano-lamine-kappa(4) N,O,O',O'')cadmium bis[2-(2-oxo-2,3-di-hydro-1,3-benzo-thia-zol-3-yl)acetate]. AB - The reaction of 2-(2-oxo-2,3-di-hydro-1,3-benzo-thia-zol-3-yl)acetic acid (NBTA) and tri-ethano-lamine (TEA) with Cd(CH3OO)2 resulted in the formation of the title salt, [Cd(C6H15NO3)2](C9H6NO3S)2. In its crystal structure, the complex cation [Cd(TEA)2](2+) and two independent NBTA(-) units with essentially similar geometries and conformations are present. In the complex cation, each TEA mol ecule behaves as an N,O,O',O''-tetra-dentate ligand, giving rise to an eight coordinate Cd(II) ion with a bicapped trigonal-prismatic configuration. All ethanol groups of each TEA mol-ecule form three five-membered chelate rings around the Cd(II) ion. The Cd-O and Cd-N distances are in the ranges 2.392 (2) 2.478 (2) and 2.465 (2)-2.475 (3) A, respectively. O-H?O hydrogen bonds between the TEA hy-droxy groups and carboxyl-ate O atoms connect cationic and anionic moieties into chains parallel to [110]. Each NBTA(-) anion is additionally linked to a symmetry-related anion through pi-pi stacking inter-actions between the benzene and thia-zoline rings [minimum centroid-to-centroid separation = 3.604 (2) A]. Together with additional C-H?O inter-actions, these establish a double layer polymeric network parallel to (001). PMID- 27375882 TI - Crystal structure of bis-(2-amino-anilinium) hydrogen phosphate. AB - The asymmetric unit of the title compound, 2C6H9N2 (+).HPO4 (2-), comprises two 2 amino-anilinium cations and one hydrogen phosphate dianion. In the crystal, the HPO4 (2-) dianions are linked by O-H?O hydrogen bonds into chains along [100]. The inorganic anionic chains and organic cations are linked by N-H?O and N-H?N hydrogen bonds, forming a two-dimensional supra-molecular network extending parallel to (001). PMID- 27375883 TI - Synthesis and crystal structure of trans-di-chlorido[3-methyl-1-(4-vinyl-benz-yl) 1H-imidazol-3-ium-2-yl-kappaC (2)](4-phenyl-pyridine-kappaN)palladium(II). AB - The title compound, [PdCl2(C11H9N)(C13H14N2)], represents a new class of palladium-based polymerizable monomer which could give a potentially catalytically active polymer. It was synthesized via transmetallation from the corresponding silver complex. The Pd(II) ion coordinates two Cl anions, one C atom from the N-heterocyclic carbene (NHC) ligand and one N atom from the 4 phenyl-pyridine ligand, displaying a slightly distorted square-planar geometry. The dihedral angle between the imidazole ring and the pyridine ring is 34.53 (8) degrees . The Pd-C bond length between the NHC ligand and the Pd(II) ion is 1.9532 (16) A. In the crystal, weak non-classical C-H?Cl hydrogen bonds link the mol-ecules into a tape structure along [101]. A weak pi-pi inter-action is also observed [centroid-centroid distance = 3.9117 (11) A]. PMID- 27375884 TI - Trinuclear nickel coordination complexes of phenanthrene-9,10-dione dioxime. AB - A trinuclear nickel complex of phenanthrene-9,10-dione dioxime (H2pqd), namely bis-[MU2-9,10-bis-(oxido-imino)-phenanthrene]-bis-[MU2-10-(oxido imino)phenanthrene-9-one oxime](phenanthrene-9,10-dione dioxime)trinickel(II) toluene disolvate, [Ni3(C14H8N2O2)2(C14H9N2O2)2(C14H10N2O2)].2C7H8, has been isolated and its crystal structure determined. This complex features three independent Ni(II) atoms that are arranged in a triangular fashion along with five supporting ligands. There are two square-planar Ni(II) atoms and a third pseudo-octa-hedral Ni(II) atom. While the square-planar Ni(II) atoms are stacked, there are no ligand bridges between them. Each square-planar Ni(II) atom, however, bridges with the pseudo-octa--hedral Ni(II) atom through Ni-N-O-Ni and Ni-O-Ni bonds. A fluorido-bor-ation reaction of the proton-bridged species gave the analogous complex bis-(MU2-bis-{[10-(oxido-imino)-9,10-di-hydro-phenanthren-9 yl-idene]amino}di-fluorido-borato)(phenanthrene-9,10-dione dioxime)trinickel(II) dichloromethane trisolvate, [Ni3(C28H16BF2N4O2)4(C14H10N2O2)].3CH2Cl2, which shows the same binding structure, but features a widened Ni-Ni inter-action between the square-planar Ni(II) atoms. The proton-bridged complex completes the macrocyclic coordination around the square-planar Ni(II) atoms by means of an O H?O hydrogen bond. Both compounds feature O-H?N hydrogen bonds between the oxime and the N atoms attached to square-planar nickel atom. The nickel units show no direct inter-action with their nearest neighbors in the extended lattice. Two pi stacking inter-actions between adjacent mol-ecules are found: one with a centroid centroid distance of 3.886 (2) A and the other with a centroid-centroid distance of 4.256 (3) A. In the latter case, although not aromatic, the distance to the centroid of the central phenanthrene ring is shorter, with a distance of 3.528 (3) A. Toluene mol-ecules occupy the solvent channels that are oriented along the c axis. In the fluorido-boronate structure, the solvent (DCM) was too badly disordered to be modelled, so its contribution was removed using SQUEEZE [Spek (2015 ?). Acta Cryst. C71, 9-18]. PMID- 27375885 TI - Crystal structures of bis-[2-(pyridin-2-yl)phenyl-kappa(2) N,C (1)]rhodium(III) complexes containing an aceto-nitrile or monodentate thyminate(1-) ligand. AB - The crystal structures of bis-[2-(pyridin-2-yl)phen-yl]rhodium(III) complexes with the metal in an octahedral coordination containing chloride and aceto nitrile ligands, namely (OC-6-42)-aceto-nitrile-chlorido-bis-[2-(pyridin-2 yl)phenyl-kappa(2) N,C (1)]rhodium(III), [RhCl(C11H8N)2(CH3CN)] (1), thyminate(1 ) and methanol, namely (OC-6-42)-methanol(5-methyl-2,4-dioxo-1,2,3,4-tetrahydro pyrimidin-1-ido-kappaN (1))bis-[2-(pyridin-2-yl)phenyl-kappa(2) N,C (1)]rhodium(III), [Rh(C11H8N)2(C5H5N2O2)(CH3OH)].CH3OH.0.5H2O (2), and thy-min ate(1-) and ethanol, namely (OC-6-42)-ethanol(5-methyl-2,4-dioxo-1,2,3,4-tetra hydro-pyrimidin-1-ido-kappaN (1))bis[2-(pyridin-2-yl)phenyl-kappa(2) N,C (1)]rhodium(III), [Rh(C11H8N)2(C5H5N2O2)(C2H5OH)].C2H5OH (3), are reported. The aceto-nitrile complex, 1, is isostructural with the Ir(III) analog. In complexes 2 and 3, the monodeprotonated thyminate (Hthym(-)) ligand coordinates to the Rh(III) atom through the N atom, and the resulting Rh-N(Hthym) bond lengths are relatively long [2.261 (2) and 2.252 (2) A for 2 and 3, respectively] as compared to the Rh-N bonds in the related thyminate complexes. In each of the crystals of 2 and 3, the complexes are linked via a pair of inter-molecular N-H?O hydrogen bonds between neighbouring Hthym(-) ligands, forming an inversion dimer. A strong intra-molecular O-H?O hydrogen bond between the thyminate(1-) and alcohol ligands in mutually cis positions to each other is also observed. PMID- 27375886 TI - Orientational disorder in the one-dimensional coordination polymer catena poly[[bis-(acetyl-acetonato-kappa(2) O,O')cobalt(II)]-MU-1,4-di-aza-bicyclo [2.2.2]octane-kappa(2) N (1):N (4)]. AB - The title compound, [Co(C5H7O2)2(C6H12N2)] n , was obtained as a one-dimensional coordination polymer from bis-(acetyl-acetonato)di-aqua-cobalt(II), [Co(acac)2(OH2)2], and 1,4-di-aza-bicyclo-[2.2.2]octane (DABCO), a di-amine with good bridging ability and rod-like spacer function. In the chain complex that extends along the c axis, the Co(II) atom is six-coordinated, the O-donor atoms of the chelating acac ligands occupying the equatorial positions and the bridging DABCO ligands being in trans-axial positions. In the crystal structure, the DABCO ligand is conformationally disordered in a 50:50 manner as a result of its location across a crystallographic mirror plane. The metal-metal distance is very close to that in a related compound exhibiting weak anti-ferromagnetic exchange between the Co(II) ions, and the title compound can thus be useful for obtaining more information about the contribution of different bridges to the magnetic coupling between paramagnetic ions. PMID- 27375887 TI - Hydrogen-bonding patterns in 5-fluoro-cytosine-melamine co-crystal (4/1). AB - The asymmetric unit of the title compound, 4C4H4FN3O.C3H6N6, comprises of two independent 5-fluoro-cytosine (5FC) mol-ecules (A and B) and one half-mol-ecule of melamine (M). The other half of the melamine mol-ecule is generated by a twofold axis. 5FC mol-ecules A and B are linked through two different homosynthons [R 2 (2)(8) ring motif]; one is formed via a pair of N-H?O hydrogen bonds and the second via a pair of N-H?N hydrogen bonds. In addition to this pairing, the O atoms of 5FC mol-ecules A and B inter-act with the N2 amino group on both sides of the melamine mol-ecule, forming a DDAA array of quadruple hydrogen bonds and generating a supra-molecular pattern. The 5FC (mol-ecules A and B) and two melamine mol-ecules inter-act via N-H?O, N-H?N and N-H?O, N-H?N, C H?F hydrogen bonds forming R 6 (6)(24) and R 4 (4)(15) ring motifs. The crystal structure is further strengthened by C-H?F, C-F?pi and pi-pi stacking inter actions. PMID- 27375888 TI - Crystal structure of 1,2-bis-[(1H-imidazol-2-yl)methylidene]hydrazine and its one dimensional hydrogen-bonding network. AB - In the title compound, C8H8N6, two imidazolyl groups are separated by a zigzag CH=N-N=CH- linkage. An inversion center is located at the mid-point of the N-N single bond and the complete molecule is generated by symmetry. In the crystal, each mol-ecule forms four N-H?N hydrogen bonds with two neighbouring mol-ecules to constitute a one-dimensional ladder-like structure propagating along the a axis direction. PMID- 27375889 TI - Crystal structure of (+/-)-[trans-cyclo-hexane-1,2-diylbis(aza-nedi-yl)]di phospho-nium dibromide dichloro-methane disolvate. AB - The cation of the title solvated salt, C42H42N2P2 (2+).2Br(-).2CH2Cl2, lies on a crystallographic twofold rotation axis. The 1,2-di-amino-cyclo-hexane fragment has a chair conformation with two N atoms in a transoid conformation [N-C-C-N = 163.4 (2) degrees ]. In the crystal, the cations are linked to the anions by N H?Br and C-H?Br hydrogen bonds, forming a chain structure along the c axis. The di-chloro-methane mol-ecule takes part in the hydrogen-bond network through C H?pi and C-H?Br inter-actions. PMID- 27375890 TI - 4-[(1-Benzyl-1H-1,2,3-triazol-4-yl)meth-oxy]benzene-1,2-dicarbo-nitrile: crystal structure, Hirshfeld surface analysis and energy-minimization calculations. AB - In the solid state, the title compound, C18H13N5O, adopts a conformation whereby the phenyl ring and meth-oxy-benzene-1,2-dicarbo-nitrile residue (r.m.s. deviation of the 12 non-H atoms = 0.041 A) lie to opposite sides of the central triazolyl ring, forming dihedral angles of 79.30 (13) and 64.59 (10) degrees , respectively; the dihedral angle between the outer rings is 14.88 (9) degrees . This conformation is nearly 7 kcal mol(-1) higher in energy than the energy minimized structure which has a syn disposition of the outer rings, enabling intra-molecular pi-pi inter-actions. In the crystal, methyl-ene-C-H?N(triazol-yl) and carbo-nitrile-N?pi(benzene) inter-actions lead to supra-molecular chains along the a axis. Supra-molecular layers in the ab plane arise as the chains are connected by benzene-C-H?N(carbo-nitrile) inter-actions; layers stack with no directional inter-actions between them. The specified inter-molecular contacts along with other, weaker contributions to the supra-molecular stabilization are analysed in a Hirshfeld surface analysis. PMID- 27375891 TI - Isoquinolinium 5-(2,4-di-nitro-phen-yl)-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetra hydro-pyrimidin-4-olate: crystal structure, Hirshfeld surface analysis and pharmacological evaluation. AB - The asymmetric unit of the title salt C9H8N(+).C12H9N4O7 (-), which exhibits anti convulsant and hypnotic activities, comprises one anion and one cation inter acting via an N-H?O hydrogen bond. In the anion, the six-membered rings are inclined each to other at 42.78 (9) degrees . The nitro groups in the 2,4-di nitro-phenyl fragment attached to the aromatic ring in the para and ortho positions are twisted from its plane by 3.1 (2) and 45.5 (2) degrees , respectively. In the crystal, weak C-H?O hydrogen bonds consolidate the crystal packing. The Hirshfeld surface analysis revealed that O?H/H?O inter-molecular contacts predominate in the crystal packing. PMID- 27375892 TI - Crystal structures of three N-(aryl-sulfon-yl)-4-fluoro-benzamides. AB - The crystal structures of three N-aryl-sulfonyl-4-fluoro-benzamides, namely 4 fluoro-N-(2-methyl-phenyl-sulfon-yl)benzamide, C14H12FNO3S, (I), N-(2-chloro phenyl-sulfon-yl)-4-fluorobenzamide, C13H9ClFNO3S, (II), and N-(4-chloro-phenyl sulfon-yl)-4-fluoro-benzamide monohydrate, C13H9ClFNO3S.H2O, (III), are described and compared with related structures. The asymmetric unit of (I) contains two independent mol-ecules (A and B), while that of (II) contains just one mol-ecule, and that of (III) contains a mol-ecule of water in addition to one main mol ecule. The dihedral angle between the benzene rings is 82.83 (11) degrees in mol ecule A and 85.01 (10) degrees in mol-ecule B of (I), compared to 89.91 (10) degrees in (II) and 81.82 (11) degrees in (III). The crystal structure of (I) features strong N-H?O hydrogen bonds between the A and B mol-ecules, resulting in an R 4 (4)(16) tetra-meric unit. These tetra-meric units are connected into sheets in the bc plane by various C-H?O inter-actions, and adjacent sheets are further inter-linked via C-H?piar-yl inter-actions, forming a three-dimensional architecture. The crystal structure is further stabilized by piar-yl-piar-yl and S=O?piar-yl inter-actions. In the crystal of (II), mol-ecules are connected into R 2 (2)(8) and R 2 (2)(14) dimers via N-H?O hydrogen bonds and C-H?O inter actions, respectively; the dimers are further inter-connected via a weak C=O?piar yl inter-action, leading to the formation of chains along [1-10]. In the crystal of (III), N-H?O and O-H?O hydrogen bonds involving both the main mol-ecule and the solvent water mol-ecule results in the formation of sheets parallel to the bc plane. The sheets are further connected by C-H?O inter-actions and weak C-Cl?piar yl, C-F?piar-yl and S=O?piar-yl inter-actions, forming a three-dimensional architecture. PMID- 27375893 TI - Crystal structures of ten enanti-opure Schiff bases bearing a naphthyl group. AB - Using a general solvent-free procedure for the synthesis of chiral Schiff bases, the following compounds were synthesized and their crystal structures determined: (S)-(+)-2-{[(1-phenyl-eth-yl)imino]-meth-yl}naphthalene, C19H17N, (1), (S)-(+)-2 ({[(4-methyl-phen-yl)eth-yl]imino}-meth-yl)naphthalene, C20H19N, (2), (R)-(-)-2 ({[(4-meth-oxy-lphen-yl)eth-yl]imino}-meth-yl)naphthalene, C20H19NO, (3), (R)-(-) 2-({[(4-fluoro-phen-yl)eth-yl]imino}-meth-yl)naphthalene, C19H16FN, (4), (S)-(+) 2-({[(4-chloro-phen-yl)eth-yl]imino}-meth-yl)naphthalene, C19H16ClN, (5), (S)-(+) 2-({[(4-bromo-phen-yl)eth-yl]imino}-meth-yl)naphthalene, C19H16BrN, (6), (S)-(+) 2-({[1-(naphthalen-1-yl)eth-yl]imino}-meth-yl)naph-thalene, C23H19N, (7), (S)-(+) 2-{[(1-cyclo-hexyl-eth-yl)imino]-meth-yl}naph-tha-lene, C19H23N, (8), (S)-(-)-2 {[(1,2,3,4-tetra-hydro-naphthalen-1-yl)imino]meth-yl}naphthalene, C21H19N, (9), and (+)-2-({[(1S,2S,3S,5R)-2,6,6-tri-methylbi-cyclo-[3.1.1]hept-3-yl]imino}-meth yl}naphthalene, C21H25N, (10). The moiety provided by the amine generates conformational flexibility for these imines. In the crystals, no strong inter molecular contacts are observed, in spite of the presence of aromatic groups. PMID- 27375894 TI - Crystal structure of fac-aquatricarbonyl[(S)-valin-ato-kappa(2) N,O]-rhenium(I). AB - In the mol-ecule of the title compound, [Re(C5H10NO2)(CO)3(H2O)], the Re(I) atom adopts a distorted octa-hedral coordination sphere defined by one aqua and three carbonyl ligands as well as one amino N and one carboxyl-ate O atom of the chelating valinate anion. The carbonyl ligands are arranged in a fac configuration around the Re(I) ion. In the crystal, an intricate hydrogen-bonding system under participation of two O-H, two N-H and one C-H donor groups and the carboxyl-ate and carbonyl O atoms as acceptor groups contribute to the formation of a three-dimensional supra-molecular network. PMID- 27375896 TI - Crystal structure of a tetranuclear Cu(II) complex with an O,N,N'-donor Schiff base ligand: hexa-MU2-acetato-bis-(2-{[(2,2,6,6-tetra-methyl-piperidin-4 yl)imino]-meth-yl}phenolato-kappa(3) O,N,N')tetra-copper(II). AB - The title compound, [Cu4(CH3COO)6(C16H23N2O)2], lies across a twofold rotation axis. The asymmetric unit contains two independent Cu(II) ions. The symmetry unique terminal Cu(II) ion is O,N,N'-coordinated by a 2-{[(2,2,6,6-tetra-methyl piperidin-4-yl)imino]-meth-yl}phenolate ligand and an O atom from an acetate group in a slightly distorted square-planar coordination environment. The symmetry-unique central Cu(II) ion is coordinated by a different O atom from the same acetate group and by four bridging acetate ligands, which connect the asymmetric unit into a dimeric complex and form a distorted square-pyramidal coordination environment. Within the complex there are two symmetry-equivalent intra-molecular N-H?O hydrogen bonds. In the crystal, weak C-H?O hydrogen bonds link the complex mol-ecules, forming a three-dimensional network. PMID- 27375895 TI - trans-2,5-Di-methyl-piperazine-1,4-diium bis(perchlorate) dihydrate: crystal structure and Hirshfeld surface analysis. AB - The asymmetric unit of the title hydrated mol-ecular salt, C6H16N2 (2+).2ClO4 ( ).2H2O, contains a half dication (completed by inversion symmetry), a perchlorate anion and a water mol-ecule. The extended structure consists of infinite chains of formula [(ClO4)H2O] n (n) (-) ions extending along the b axis linked by Ow-H?O (w = water) hydrogen bonds. These chains are cross-linked by the dications via N H?Ow and weak C-H?O hydrogen bonds, thus forming a three-dimensional supra molecular network. Three-dimensional Hirshfeld surface analysis and two dimensional fingerprint maps reveal that the structure is dominated by H?O/O?H and H?H contacts. PMID- 27375897 TI - Crystal structure of 4'-bromo-2',5'-dimeth-oxy-2,5-dioxo-[1,1'-biphen-yl]-3,4 dicarbo-nitrile [BrHBQ(CN)2] benzene hemisolvate. AB - In the crystal of the title compound, C16H9BrN2O4.0.5C6H6, the mol-ecules stack in a centrosymmetric unit cell in a 2:1 stoichiometry with co-crystallized benzene solvent mol-ecules and inter-act via various weak inter-actions. This induces a geometry different from that predicted by theory, and is unique among the hemibi-quinones heretofore reported. PMID- 27375898 TI - HIV-host interactome revealed directly from infected cells. AB - Although genetically compact, HIV-1 commandeers vast arrays of cellular machinery to sustain and protect it during cycles of viral outgrowth. Transposon-mediated saturation linker scanning mutagenesis was used to isolate fully replication competent viruses harbouring a potent foreign epitope tag. Using these viral isolates, we performed differential isotopic labelling and affinity-capture mass spectrometric analyses on samples obtained from cultures of human lymphocytes to classify the vicinal interactomes of the viral Env and Vif proteins as they occur during natural infection. Importantly, interacting proteins were recovered without bias, regardless of their potential for positive, negative or neutral impact on viral replication. We identified specific host associations made with trimerized Env during its biosynthesis, at virological synapses, with innate immune effectors (such as HLA-E) and with certain cellular signalling pathways (for example, Notch1). We also defined Vif associations with host proteins involved in the control of nuclear transcription and nucleoside biosynthesis as well as those interacting stably or transiently with the cytoplasmic protein degradation apparatus. Our approach is broadly applicable to elucidating pathogen host interactomes, providing high-certainty identification of interactors by their direct access during cycling infection. Understanding the pathophysiological consequences of these associations is likely to provide strategic targets for antiviral intervention. PMID- 27375899 TI - Differences in Central Corneal Thickness between Spectral Domain-Optical Coherence Tomography and Ultrasound Pachymetry in Patients with Dry Eye Disease. AB - Purpose. To compare central corneal thickness (CCT) values via Spectral Domain Optical Coherence Tomography (SD-OCT) and ultrasonic pachymetry in patients with severe dry eye disease (DED) to determine the level of agreement between these 2 methods. Methods. The paired samples t-test was used to compare CCT values in severe DED patients. Matching analysis between methods was performed using intraclass correlation coefficient (ICC). Intrasession reliability of the measurement methods was calculated via the concordance correlation coefficient (CCC), variation equivalent, and Pearson's correlation coefficient. The Bland Altman procedure was used to graphically represent the differences between CCT values. Results. The study included 56 eyes of 24 female and 4 male patients. Mean age of the patients was 50.9 +/- 11.3 years. Mean CCT via Cirrus SD-OCT was 523.82 +/- 30.98 MUm versus 530.050 +/- 31.85 MUm via ultrasonic pachymetry (paired samples t-test, P < 0.001). The Bland-Altman plot showed good agreement between the examiners. The ICC for repeatability was 0.974. The CCC between the 2 methods' CCT values was 0.973. The variation equivalent was 0.976 and Pearson's correlation coefficient was 99.3%, which also indicated high correlation between the 2 methods' measurements. Conclusions. The present findings show that in patients with severe DED Cirrus SD-OCT provides reliable intraobserver CCT values. PMID- 27375900 TI - A Systematic Review and Meta-Analysis of Outcomes for Type 1 Diabetes after Bariatric Surgery. AB - Background. The utility of bariatric surgery in type 1 diabetes remains controversial. The aim of the present study is to evaluate glycemic control outcomes in obese patients with type 1 diabetes after bariatric surgery. Methods. A comprehensive search of electronic databases was completed. Inclusion criteria included human adult subjects with BMI >=35 kg/m(2) and a confirmed diagnosis of type 1 diabetes who underwent a bariatric surgical procedure. Results. Thirteen primary studies (86 patients) were included. Subjects had a mean age of 41.16 +/- 6.76 years with a mean BMI of 42.50 +/- 2.65 kg/m(2). There was a marked reduction in BMI postoperatively at 12 months and at study endpoint to 29.55 +/- 1.76 kg/m(2) (P < 0.00001) and 30.63 +/- 2.09 kg/m(2) (P < 0.00001), respectively. Preoperative weighted mean total daily insulin requirement was 98 +/- 26 IU/d, which decreased significantly to 36 +/- 15 IU/d (P < 0.00001) and 42 +/- 11 IU/d (P < 0.00001) at 12 months and at study endpoint, respectively. An improvement in HbA1c was also seen from 8.46 +/- 0.78% preoperatively to 7.95 +/- 0.55% (P = 0.01) and 8.13 +/- 0.86% (P = 0.03) at 12 months and at study endpoint, respectively. Conclusion. Bariatric surgery in patients with type 1 diabetes leads to significant reductions in BMI and improvements in glycemic control. PMID- 27375901 TI - Accuracy of Transcutaneous Carbon Dioxide Measurement in Premature Infants. AB - Background. In premature infants, maintaining blood partial pressure of carbon dioxide (pCO2) value within a narrow range is important to avoid cerebral lesions. The aim of this study was to assess the accuracy of a noninvasive transcutaneous method (TcpCO2), compared to blood partial pressure of carbon dioxide (pCO2). Methods. Retrospective observational study in a tertiary neonatal intensive care unit. We analyzed the correlation between blood pCO2 and transcutaneous values and the accuracy between the trends of blood pCO2 and TcpCO2 in all consecutive premature infants born at <33 weeks' gestational age. Results. 248 infants were included (median gestational age: 29 + 5 weeks and median birth weight: 1250 g), providing 1365 pairs of TcpCO2 and blood pCO2 values. Pearson's R correlation between these values was 0.58. The mean bias was 0.93 kPa with a 95% confidence limit of agreement of -4.05 to +2.16 kPa. Correlation between the trends of TcpCO2 and blood pCO2 values was good in only 39.6%. Conclusions. In premature infants, TcpCO2 was poorly correlated to blood pCO2, with a wide limit of agreement. Furthermore, concordance between trends was equally low. We warn about clinical decision-making on TcpCO2 alone when used as continuous monitoring. PMID- 27375903 TI - Active Ageing Level of Older Persons: Regional Comparison in Thailand. AB - Active ageing level and its discrepancy in different regions (Bangkok, Central, North, Northeast, and South) of Thailand have been examined for prioritizing the policy agenda to be implemented. Attempt has been made to test preliminary active ageing models for Thai older persons and hence active ageing index (AAI, ranges from 0 to 1) has been estimated. Using nationally representative data and confirmatory factor analysis approach, this study justified active ageing models for female and male older persons in Thailand. Results revealed that active ageing level of Thai older persons is not high (mean AAIs for female and male older persons are 0.64 and 0.61, resp., and those are significantly different (p < 0.001)). Mean AAI in Central region is lower than North, Northeast, and South regions but there is no significant difference in the latter three regions of Thailand. Special emphasis should be given to Central region and policy should be undertaken for increasing active ageing level. Implementation of an Integrated Active Ageing Package (IAAP), containing policies for older persons to improve their health and economic security, to promote participation in social groups and longer working lives, and to arrange learning programs, would be helpful for increasing older persons' active ageing level in Thailand. PMID- 27375902 TI - Molecular and Growth-Based Drug Susceptibility Testing of Mycobacterium tuberculosis Complex for Ethambutol Resistance in the United States. AB - Ethambutol (EMB) is used as a part of drug regimens for treatment of tuberculosis (TB). Susceptibility of Mycobacterium tuberculosis complex (MTBC) isolates to EMB can be discerned by DNA sequencing to detect mutations in the embB gene associated with resistance. US Public Health Laboratories (PHL) primarily use growth-based drug susceptibility test (DST) methods to determine EMB resistance. The Centers for Disease Control and Prevention (CDC) provides a service for molecular detection of drug resistance (MDDR) by DNA sequencing and concurrent growth-based DST using agar proportion. PHL and CDC test results were compared for 211 MTBC samples submitted to CDC from September 2009 through February 2011. Concordance between growth-based DST results from PHL and CDC was 88.2%. A growth based comparison of 39 samples, where an embB mutation associated with EMB resistance was detected, revealed a higher percentage of EMB resistance by CDC (84.6%) than by PHL (59.0%) which was significant (P value = 0.002). Discordance between all growth-based test results from PHL and CDC was also significant (P value = 0.003). Most discordance was linked to false susceptibility using the BACTECTM MGITTM 960 (MGIT) growth-based system. Our analysis supports coalescing growth-based and molecular results for an informed interpretation of potential EMB resistance. PMID- 27375904 TI - Dynamic Changes in Local Protein Synthetic Machinery in Regenerating Central Nervous System Axons after Spinal Cord Injury. AB - Intra-axonal localization of mRNAs and protein synthesis machinery (PSM) endows neurons with the capacity to generate proteins locally, allowing precise spatiotemporal regulation of the axonal response to extracellular stimuli. A number of studies suggest that this local translation is a promising target to enhance the regenerative capacity of damaged axons. Using a model of central nervous system (CNS) axons regenerating into intraspinal peripheral nerve grafts (PNGs) we established that adult regenerating CNS axons contain several different mRNAs and protein synthetic machinery (PSM) components in vivo. After lower thoracic level spinal cord transection, ascending sensory axons regenerate into intraspinal PNGs but axon growth is stalled when they reach the distal end of the PNG (3 versus 7 weeks after grafting, resp.). By immunofluorescence with optical sectioning of axons by confocal microscopy, the total and phosphorylated forms of PSMs are significantly lower in stalled compared with actively regenerating axons. Reinjury of these stalled axons increased axonal localization of the PSM proteins, indicative of possible priming for a subcellular response to axotomy. These results suggest that axons downregulate protein synthetic capacity as they cease growing, yet they retain the ability to upregulate PSM after a second injury. PMID- 27375905 TI - Cervical Necrotizing Fasciitis Caused by Dental Extraction. AB - Cervical necrotizing fasciitis is an unusual infection characterized by necrosis of the subcutaneous tissue and fascial layers. Risk factors for the development of necrotizing fasciitis include diabetes mellitus, chronic renal disease, peripheral vascular disease, malnutrition, advanced age, obesity, alcohol abuse, intravenous drug use, surgery, and ischemic ulcers. This report presents a case of necrotizing fasciitis in the cervical area caused by dental extraction in a 73 year-old woman. Cervical necrotizing fasciitis in geriatric patient is rare, and even when establishing the diagnosis and having it timely treated, the patient can suffer irreversible damage or even death. Clinical manifestations in the head and neck usually have an acute onset characterized by severe pain, swelling, redness, erythema, presence of necrotic tissue, and in severe cases obstruction of the upper airways. Therefore, the presentation of this clinical case can serve as guidance to dentists as a precaution to maintain an aseptic chain and be aware of the clinical condition of older patients and the systemic conditions that may increase the risk of infections. PMID- 27375906 TI - New Parameter for In-Office Dental Bleaching. AB - Dental bleaching is considered a conservative and biologically safe treatment for discolored teeth. Despite this, one of the major undesirable effects of bleaching is dentin sensitivity which may occur during and after treatment. To address these sensitivity issues, new dental bleaching preparations with lower concentrations of hydrogen peroxide (H2O2) have recently been introduced to the market. This paper presents a clinical case report of a 20-year-old female patient admitted to the Araraquara Dental School, UNESP, Brazil. The patient underwent dental bleaching using one of the new products with reduced hydrogen peroxide concentration, Lase Peroxide Lite 6%, a 6% H2O2 gel containing titanium oxide nanoparticles doped with nitrogen (6% H2O2/N-doped TiO2). PMID- 27375907 TI - Adrenal Insufficiency under Standard Dosage of Glucocorticoid Replacement after Unilateral Adrenalectomy for Cushing's Syndrome. AB - Glucocorticoid replacement is needed for patients after adrenal surgery for Cushing's syndrome; however, the adequate dosage is not easily determined. The patient was a 62-year-old woman who has had hypertension for 5 years and presented with heart failure due to hypertrophic cardiomyopathy. She consulted with us because of general fatigue, facial edema, and muscle weakness and was diagnosed with Cushing's syndrome. A laparoscopic left adrenalectomy was performed, standard dosage of postoperative replacement was administered, and she was discharged with 30 mg/day of hydrocortisone (cortisol). However, she suffered from loss of appetite and was transferred to an emergency unit with the symptoms of adrenal insufficiency on postoperative day 15. After initial hydrocortisone replacement with 200 mg/day, the dosage was gradually decreased during hospitalization; however, reduction of hydrocortisone dosage lower than 60 mg/day was difficult because of nausea and fatigue. Her circadian cortisol profile after hydrocortisone administration showed delayed and lowered peaks, which suggested that hydrocortisone absorption in the intestine was impaired. Therefore, complicated heart failure may have led to the adrenal insufficiency in the patient. In such cases, we should consider postoperative administration of more than the standard dosage of hydrocortisone to avoid adrenal insufficiency after surgery for Cushing's syndrome. PMID- 27375908 TI - Common Hepatic Duct Mixed Adenoneuroendocrine Carcinoma Masquerading as Cholangiocarcinoma. AB - Bile duct mixed adenoneuroendocrine carcinoma (MANEC) is a rare entity. It is defined as having mixed elements of both neuroendocrine tumors (NET) and an adenocarcinoma element, the lesser component forming at least 30% of the tumor. It is a subtype of neuroendocrine carcinoma (NEC) showing both gland-forming epithelial tumor cells and neuroendocrine cells. It is generally misdiagnosed as cholangiocarcinoma on imaging studies. The preoperative pathological workup from the endoscopic retrograde cholangiography brush cytology usually misses the NET/NEC component since it often lies deeper in the tumor. However, it is reported that it is the NEC component that defines the prognosis of the tumor; hence, it is vital to identify the NEC component. We present a rare case of common hepatic duct (CHD) MANEC that was preoperatively misdiagnosed as cholangiocarcinoma. PMID- 27375909 TI - Adult Prader-Willi Syndrome: An Update on Management. AB - With the advancement of medical care, the survival of most patients with syndromal genetic disease is greatly improved. In this case report, we have reported an adult Prader-Willi syndrome patient who is being diagnosed at the age of 33. The clinical features and their associated complications during adulthood have been reviewed. PMID- 27375910 TI - Nonobstructive Acute Renal Failure with a Large Solitary Fibroid. AB - A 38-year-old African American woman presenting with acute abdominal pain and nonobstructive renal failure was found to have an enlarged fibroid uterus. A differential for sepsis was considered. Lab evaluation revealed an elevated creatinine and myoglobin level at 3.9 mg/dL and 2140 ng/mL, respectively. Ongoing hemodynamic instability mandated surgery for acute abdomen. A 25 cm fibroid uterus was extirpated through a total abdominal hysterectomy. Immediate improvement of acute nephropathy mirrored the postoperative decline in serum myoglobin levels. Myoglobinemia from a massive degenerating fibroid is associated with nonobstructive acute renal failure. PMID- 27375911 TI - Placenta Increta Complicating Persistent Cesarean Scar Ectopic Pregnancy following Failed Excision with Subsequent Preterm Cesarean Hysterectomy. AB - Introduction. Cesarean scar pregnancies (CSPs) are one of the rarest forms of ectopic pregnancy. Given their rarity, there is lack of consensus regarding the management and natural course of CSPs. Case. A 37-year-old G10 P3063 female with a history of two prior cesarean deliveries was diagnosed with her second CSP at 6 weeks and 5 days in her tenth pregnancy. The patient underwent vertical hysterotomy, excision of a gestational sac implanted in the cesarean sac, and bilateral salpingectomy via a laparotomy incision. The histopathology report confirmed immature chorionic villi. The patient returned 10 weeks later and was found to be still pregnant. Obstetric ultrasound confirmed a viable fetus of 19 weeks and 4 days of gestational age with a thin endometrium and an anteroposterior and right lateral placenta with multiple placental lakes. The patient ruptured her membranes at 31 weeks of gestation and pelvic MRI revealed an anterior placenta invading the myometrium and extending to the external serosal surface consistent with placenta increta. Following obstetric interventions, a live female infant was delivered by cesarean hysterectomy (because of placenta increta) at 32 weeks of gestation. Conclusion. Development of standardized guidelines for management of CSPs, as well as heightened vigilance for possible complications, is required for proper care and avoidance of potential morbidity and mortality. PMID- 27375912 TI - Metastatic Malignant Ovarian Steroid Cell Tumor: A Case Report and Review of the Literature. AB - We report a case of malignant ovarian steroid cell tumor not otherwise specified (NOS) in a 47-year-old female who presented with hirsutism, virilization, and amenorrhea. At the time of laparotomy, the tumor had already spread to the pelvic cul-de-sac. She underwent a total hysterectomy, bilateral salpingo-oophorectomy, and tumor resection with no residual disease. She received three cycles of bleomycin, etoposide, and cisplatin (BEP) and is now free of disease 24 months after surgery. Literature review of ovarian steroid cell tumors NOS including clinicopathological features and clinical management was performed. PMID- 27375913 TI - Ophthalmic Manifestations of Hematopoietic Malignancy. AB - Purpose. To report the ocular findings in patients with hematopoietic malignancy with optic nerve involvement and abducens nerve palsy. Methods. The medical records of all cases of hematopoietic cancer with ophthalmic involvements seen in the Department of Ophthalmology of the National Center for Global Health and Medicine between 2009 and 2014 were reviewed. Results. Eight patients with hematopoietic cancer with optic nerve invasion or abducens nerve palsy were studied. The primary diseases were 3 cases of multiple myeloma, 1 case of acute lymphocytic leukemia, 1 case of follicular lymphoma, and 3 cases of AIDS-related lymphoma. Six cases had optic nerve invasion, 2 cases had abducens nerve palsy, and 1 case had optic nerve invasion of both eyes. The median visual acuity of eyes with optic nerve invasion was 0.885 logarithm of the minimum angle of resolution (logMAR) units. The final visual acuity of eyes with optic nerve invasion was 1.25 logMAR units, and that of those with sixth-nerve palsy was -0.1 logMAR units. Six cases died during the five-year follow-up period. An ophthalmic involvement in patients with hematopoietic cancer, especially AIDS-related lymphoma, was associated with poor prognosis. Conclusion. Because ophthalmic involvement in patients with hematopoietic malignancy has a poor prognosis, an early diagnosis of the cancers by the ophthalmologic findings by ophthalmologists could improve the prognosis. PMID- 27375914 TI - Supraglottic Kaposi's Sarcoma in HIV-Negative Patients: Case Report and Literature Review. AB - This paper presents a case report of an HIV-negative, supraglottic Kaposi's sarcoma patient. The 80-year-old male patient was admitted with complaints of hoarseness, difficulty in swallowing, and a stinging sensation in his throat for approximately six months. The endoscopic larynx examination revealed a lesion which had completely infiltrated the epiglottis, reached right aryepiglottic fold, was vegetating, pink and purple in color, multilobular, fragile, and shaped like a bunch of grapes, and partially blocked the bleeding airway passage. The case was discussed by the hospital's head-neck cancer committee and a surgery decision was made. A tracheotomy was performed under local anesthesia before the operation due to respiratory distress and endotracheal intubation difficulty. Direct laryngoscopy showed that the mass was limited in the supraglottic area, had invaded the entire left aryepiglottic fold and one-third of the front right aryepiglottic fold, and completely covered epiglottis. It should be remembered that although rare, Kaposi's sarcoma may be encountered in larynx malignancy cases. Disease-free survival may be achieved through local excision and postoperative radiotherapy. PMID- 27375915 TI - Endovascular Embolization of an Aberrant Bronchial Artery Originating from the Internal Mammary Artery in a Patient with Hemoptysis. AB - Massive hemoptysis is a life threatening respiratory emergency with high mortality and the bronchial artery (BA) is its most frequent source. Herein, we report a case of a 76-year-old man with recurrent hemoptysis due to an aberrant right BA arising from the right internal mammary artery (IMA), an extremely rare origin, that was clearly depicted on pretreatment computed tomography angiography (CTA). The patient was treated successfully by transcatheter bronchial artery embolization (BAE) of the aberrant BA and the hemoptysis has since been controlled for 9 months. Knowledge of the detailed BA anatomy is essential for performing BAE, especially in cases of aberrant BA. CTA is a promising tool for pretreatment planning of emergency BAE in patients with hemoptysis. PMID- 27375916 TI - Catastrophic Antiphospholipid Syndrome. AB - This paper reports one case of successfully treated patients suffering from a rare entity, the catastrophic antiphospholipid syndrome (CAPS). Management of this patient is discussed in detail. PMID- 27375917 TI - Multiple Gastric Gastrointestinal Stromal Tumors in a Patient with Neurofibromatosis Type 1. AB - Gastrointestinal stromal tumors (GISTs) are relatively common in neurofibromatosis type 1 (NF 1) patients. Approximately 90% of GISTs associated with NF 1 are located in the small intestine, while sporadic GISTs are most commonly located in the stomach. Here we report an extremely rare case of an NF 1 patient with multiple gastric GITs (90 or more) but without multiple small intestinal tumors. A 63-year-old female patient who had a history of NF 1 underwent surgery for a gastric neuroendocrine tumor and gastric submucosal tumor (SMT). During the operation, multiple small nodules were identified on the serosal surface of the upper stomach. SMT and multiple nodules on the serosal surface were diagnosed as GISTs consisting of spindle cells positive for KIT, CD34, and DOG-1. Both GIST and the normal gastric mucosa showed no mutations not only in the c-kit gene (exons 8, 9, 11, 13, and 17) but also in the PDGFRA gene (exons 12, 14, and 18). This patient is being followed up without the administration of a tyrosine kinase inhibitor. PMID- 27375918 TI - The Association between C9orf72 Repeats and Risk of Alzheimer's Disease and Amyotrophic Lateral Sclerosis: A Meta-Analysis. AB - C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in Caucasian populations. However, the relationship between C9orf72 repeats and Alzheimer's disease (AD) was not clear. Additionally, there were few articles assessing C9orf72 in other ethnicities with ALS. In this meta-analysis, we aimed to investigate the relationship between C9orf72 repeat expansions (>=30 repeats) and intermediate repeat copies (20-29 repeats) and AD or ALS. The results suggested positive correlations between C9orf72 repeat expansions and the risk of Alzheimer's disease (OR = 6.36, 95% CI = 3.13-12.92, and p < 0.00001), while intermediate repeat copies of C9orf72 gene were not associated with the risk of the disease. C9orf72 repeat expansions were positively correlated with the risk of familial and sporadic ALS (OR = 293.25, 95% CI = 148.17-580.38, and p < 0.00001; OR = 35.57, 95% CI = 19.61-64.51, and p < 0.00001). There was a positive correlation between the gene variations and ALS risk among Caucasians and Asians (OR = 57.56, 95% CI = 36.73-90.22, and p < 0.00001; OR = 6.35, 95% CI = 1.39-29.02, and p = 0.02). PMID- 27375919 TI - Identification and Discrimination of Brands of Fuels by Gas Chromatography and Neural Networks Algorithm in Forensic Research. AB - The detection of adulteration of fuels and its use in criminal scenes like arson has a high interest in forensic investigations. In this work, a method based on gas chromatography (GC) and neural networks (NN) has been developed and applied to the identification and discrimination of brands of fuels such as gasoline and diesel without the necessity to determine the composition of the samples. The study included five main brands of fuels from Spain, collected from fifteen different local petrol stations. The methodology allowed the identification of the gasoline and diesel brands with a high accuracy close to 100%, without any false positives or false negatives. A success rate of three blind samples was obtained as 73.3%, 80%, and 100%, respectively. The results obtained demonstrate the potential of this methodology to help in resolving criminal situations. PMID- 27375920 TI - Knowledge about Danger Signs of Obstetric Complications and Associated Factors among Postnatal Mothers of Mechekel District Health Centers, East Gojjam Zone, Northwest Ethiopia, 2014. AB - Background. Developing countries like Ethiopia contributed highest level of maternal mortality due to obstetric complications. Women awareness of obstetric danger sign to recognize complications to seek medical care early is the first intervention in an effort to decrease maternal death. Objective. To assess knowledge about danger signs of obstetric complications and associated factors among postnatal mothers at Mechekel district health centers, East Gojjam zone, Northwest Ethiopia, 2014. Methods. An institution based cross-sectional study was conducted from August to October, 2014, in Mechekel district health centers. Systematic random sampling was used to select four hundred eleven study participants. A pretested structured questionnaire was used to collect data. Data were entered to Epi Info version 3.5.3 and exported to SPSS 20.0 for further analysis. Descriptive and summary statistics were done. Logistic regression analyses were used to see the association of different variables. Odds ratios and 95% confidence interval were computed to determine the presence and strength of association. Results. According to this study, 55.1% participants were knowledgeable about danger signs of obstetric complications. Maternal and husband educational level ((AOR = 1.977, 95% CI: 1.052, 3.716) and (AOR = 3.163, 95% CI: 1.860, 5.3770), resp.), family monthly income >= 1500 (AOR = 2.954, 95% CI: 1.289, 6.770), being multipara (AOR = 7.463, 95% CI: 1.301, 12.800), ANC follow up during last pregnancy (AOR = 2.184, 95% CI: 1.137, 4.196), and place of last delivery (AOR = 1.955, 95% CI: 1.214, 3.150) were variables found to be significantly associated with women's knowledge on danger signs of obstetric complications. Conclusion. Significant proportion of respondents were not knowledgeable about obstetric danger signs and factors like educational status, place of last delivery, and antenatal follow-up were found to be associated. PMID- 27375921 TI - Properties of Particle Size Distribution from Milled White Nixtamalized Corn Kernels as a Function of Steeping Time. AB - This paper focuses on the particle size distribution (PSD) changes during nixtamalized corn kernels (NCK) as a function of the steeping time (ST). The process to obtain powder or corn flour from NCK was as follows: (i) the NCK with different STs were wet-milled in a stone mill, (ii) dehydrated by a Flash type dryer, and (iii) pulverized with a hammer mill and sieved with a 20 mesh. The powder was characterized by measuring the PSD percentage, calcium percentage (CP), peak viscosity at 90 degrees C (PV), and crystallinity percentage (CP). The PSD of the powder as a function of ST was determined by sieving in Ro-TAP equipment. By sieving, five fractions of powder were obtained employing meshes 30, 40, 60, 80, and 100. The final weight of the PSD obtained from the sieving process follows a Gaussian profile with the maximum corresponding to the average particle obtained with mesh 60. The calcium percentage as a function of ST follows a behavior similar to the weight of the PSD. The study of crystallinity versus the mesh number shows that it decreases for smaller mesh number. A similar behavior is observed as steeping time increases, except around ST = 8 h where the gelatinization of starch is observed. The trend of increasing viscosity values of the powder samples occurs when increasing ST and decreasing particle size. The ST significantly changes the crystallinity and viscosity values of the powder and, in both cases, a minimum value is observed in the region 7-9 h. The experimental results show that the viscosity increases (decreases) if the particle size decreases (increases). PMID- 27375922 TI - Addressing Benefits, Risks and Consent in Next Generation Sequencing Studies. AB - The sequencing of the human genome and technological advances in DNA sequencing have led to a revolution with respect to DNA sequencing and its potential to diagnose genetic disorders. However, requests for open access to genomic data must be balanced against the guiding principles of the Common Rule for human subject research. Unfortunately, the risks to patients involved in genomic studies are still evolving and as such may not be clear to learned and well intentioned scientists. Central to this issue are the strategies that enable human participants in such studies to remain anonymous, or de-identified. The wealth of genomic data on the Internet in genomic data repositories and other databases has enabled de-identified data to be broken and research subjects to be identified. The security of de-identification neglects the fact that DNA itself is an identifying element. Therefore, it is questionable whether data security standards can ever truly protect the identity of a patient, under the current conditions or in the future. As Big Data methodologies advance, additional sources of data may enable the re-identification of patients enrolled in next generation sequencing (NGS) studies. As such, it is time to re-evaluate the risks of sharing genomic data and establish new guidelines for good practices. In this commentary, I address the challenges facing federally funded investigators who need to strike a balance between compliance with federal (US) rules for human subjects and the recent requirement for open access/sharing of data from National Institute for Health (NIH)-funded studies involving human subjects. PMID- 27375923 TI - E. coli Heat-labile Enterotoxin B Subunit as a Platform for the Delivery of HIV Gag p24 Antigen. AB - Multiple vaccination strategies have been devised against HIV-1 including delivery of HIV moieties in attenuated or replication defective recombinant microbial agents alone or in combination with priming agents in form of soluble proteins or naked DNA. For the priming agents to be effective, adjuvants might be essential in directing the immune response to a desired outcome. E. coli enterotoxin B subunit (LTB) is an effective adjuvant and carrier for other proteins and epitopes. Here we show that conjugation of HIV gag p24 to LTB enhances the T cell response to gag p24 by increasing rate of T cell division compared to other treatments. Because HIV vaccines are likely to be multivalent, we further investigated whether gag p24 inhibits antigen presentation of an unrelated antigen, OVA. Addition of gag p24 to OVA-responsive DO.11.10 cell culture did not have adverse effects on antigen presentation. Interestingly, the presence of LTB in these cultures significantly increased proliferation of DO.11.10 cells. In all, the results suggest the use of LTB to boost immune responses against HIV gag p24 in systemic priming regimens with oral recombinant HIV vaccines. PMID- 27375924 TI - The Quest for an HIV-1 Vaccine Adjuvant: Bacterial Toxins as New Potential Platforms. AB - While tremendous efforts are undergoing towards finding an effective HIV-1 vaccine, the search for an HIV-1 vaccine adjuvant lags behind and is understudied. More recently, however, efforts have focused on testing adjuvant formulations that can boost the immune response and generate broadly neutralizing antibodies to HIV-1 ENV (gp160). Despite this, there remain a number of challenges towards achieving this goal. These include safety of adjuvant formulations; stability of the incorporated antigens; maintenance of ENV immunogenicity; optimal inoculation sites; the effective combination of adjuvants; stability of ENV neutralizing epitopes in some adjuvant formulations; mucosal immunity; and long-term maintenance of the immune response. A new class of adjuvants for HIV-1 proteins is suggested to overcome many of the limitations of some other adjuvants. Type 1 (LT-I) and type 2 (LT-II) human E. coli enterotoxins (HLTs) and their non-toxic B-subunits derivatives are strong systemic and mucosal adjuvants and effective carriers for other proteins and epitopes. Their stable molecular structure in the presence of fused proteins and epitopes, and their ability to target surface receptors on antigen presenting cells make them ideal for the delivery of HIV-1 ENV or HIV other proteins. Importantly, unlike some other adjuvants, HLTs and derivatives have well-defined modes of immune system activation. The challenges in finding optimal HIV-1 vaccine adjuvant formulation and the important properties of HLTs are discussed. PMID- 27375925 TI - Antibodies to the RNA Binding Protein Heterogeneous Nuclear Ribonucleoprotein A1 Colocalize to Stress Granules Resulting in Altered RNA and Protein Levels in a Model of Neurodegeneration in Multiple Sclerosis. AB - OBJECTIVE: Multiple sclerosis (MS) is the most common demyelinating disorder of the central nervous system (CNS). Data suggest that antibodies to CNS targets contribute to the pathogenesis of MS. MS patients produce autoantibodies to heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1). hnRNP A1 is an RNA binding protein (RBP) overexpressed in neurons that functions in pre-mRNA splicing, mRNA trafficking, and translation. Previously, we showed that anti-hnRNP A1 antibodies entered neuronal cells (in vitro) via clathrin-mediated endocytosis, caused mislocalization of endogenous hnRNP A1 protein and increased markers of neurodegeneration including decreased ATP concentration and apoptosis. In this study, we hypothesized that anti-hnRNP A1 antibodies might cause stress granule formation and altered levels of RNAs and proteins that bind hnRNP A1. METHODS: Neuronal cell lines were exposed to anti-hnRNP A1 and isotype-matched control antibodies in vitro and examined for neuronal granule formation, including stress granules, P bodies and transport granules. In addition, RNAs that bound hnRNP A1 were determined. Levels of RNA and their translated proteins were measured upon exposure to the anti-hnRNP A1 antibodies. RESULTS: Anti-hnRNP A1 antibodies induced and localized to stress granules, a marker of neurodegeneration, within a neuronal cell line. The anti-hnRNP A1 antibodies did not induce P bodies or neuronal granules. Clinically relevant RNAs were found to bind hnRNP A1. In addition, the anti-hnRNP A1 antibodies caused reduced levels of RNA and protein of the spinal paraplegia genes (SPGs) 4 and 7, which when mutated mimic progressive MS. CONCLUSIONS: Taken together, these data suggest potential mechanisms by which autoantibodies may contribute to neurodegeneration in MS. PMID- 27375926 TI - Particle streak velocimetry-optical coherence tomography: a novel method for multidimensional imaging of microscale fluid flows. AB - We present a new OCT method for flow speed quantification and directional velocimetry: particle streak velocimetry-OCT (PSV-OCT). PSV-OCT generates two dimensional, 2.5-vector component (vx ,|vy |,vz ) maps of microscale flow velocity fields. Knowledge of 2.5-vector components also enables the estimation of total flow speed. The enabling insight behind PSV-OCT is that tracer particles in sparsely-seeded fluid flow trace out streaks in (x,z,t)-space. The streak orientations in x-t and z-t yield vx and vz , respectively. The in-plane (x-z plane) residence time yields the out-of-plane speed |vy |. Vector component values are generated by fitting streaks to a model of image formation that incorporates equations of motion in 3D space. We demonstrate cross-sectional estimation of (vx ,|vy |,vz ) in two important animal models in ciliary biology: Xenopus embryos (tadpoles) and mouse trachea. PMID- 27375927 TI - In vivo optical monitoring of transcutaneous delivery of calcium carbonate microcontainers. AB - We have developed a method for delivery of biocompatible CaCO3 microcontainers (4.0 +/- 0.8 um) containing Fe3O4 nanoparticles (14 +/- 5 nm) into skin in vivo using fractional laser microablation (FLMA) provided by a pulsed Er:YAG laser system. Six laboratory rats have been used for the microcontainer delivery and weekly monitoring implemented using an optical coherence tomography and a standard histological analysis. The use of FLMA allowed for delivery of the microcontainers to the depth about 300 MUm and creation of a depot in dermis. On the seventh day we have observed the dissolving of the microcontainers and the release of nanoparticles into dermis. PMID- 27375928 TI - Nanoparticle-free tissue-mimicking phantoms with intrinsic scattering. AB - We present an alternative to the conventional approach, phantoms without scattering nanoparticles, where scattering is achieved by the material itself: spherical cavities trapped in a silicone matrix. We describe the properties and fabrication of novel optical phantoms based on a silicone elastomer polydimethylsiloxane (PDMS) and glycerol mixture. Optical properties (absorption coefficient ua , reduced scattering coefficient us' , and anisotropy factor g) of the fabricated phantoms were retrieved from spectrophotometric measurements (in the 400-1100 nm wavelength range) using the inverse adding-doubling method. The internal structure of the phantoms was studied under a scanning electron microscope, and the chemical composition was assessed by Raman spectroscopy. Composition of the phantom material is reported along with the full characterization of the produced phantoms and ways to control their parameters. PMID- 27375929 TI - Noninvasive and high-resolving photoacoustic dermoscopy of human skin. AB - We proposed and developed a photoacoustic (PA) dermoscope equipped with an integrated PA probe to achieve quantification and high-resolution, high-contrast deep imaging of human skin. The PA probe, with light-sound confocal excitation and reception, is specially designed, and integrated with an objective lens, an ultrasound transducer, and an inverted-triangle coupling cup to facilitate convenient implementation in a clinical setting. The PA dermoscope was utilized for noninvasive and high-resolution imaging of epidermal and dermal structure in volunteers. The imaging results demonstrated that the characteristic parameters of skin disease, including pigment distribution and thickness, vascular diameter, and depth, can be obtained by the PA dermoscope, confirming that PA dermoscopy can serve as a potential tool for the diagnosis and curative effect evaluation of human skin disease. PMID- 27375930 TI - Reconstruction of burst activity from calcium imaging of neuronal population via Lq minimization and interval screening. AB - Calcium imaging is becoming an increasingly popular technology to indirectly measure activity patterns in local neuronal networks. Based on the dependence of calcium fluorescence on neuronal spiking, two-photon calcium imaging affords single-cell resolution of neuronal population activity. However, it is still difficult to reconstruct neuronal activity from complex calcium fluorescence traces, particularly for traces contaminated by noise. Here, we describe a robust and efficient neuronal-activity reconstruction method that utilizes Lq minimization and interval screening (IS), which we refer to as LqIS. The simulation results show that LqIS performs satisfactorily in terms of both accuracy and speed of reconstruction. Reconstruction of simulation and experimental data also shows that LqIS has advantages in terms of the recall rate, precision rate, and timing error. Finally, LqIS is demonstrated to effectively reconstruct neuronal burst activity from calcium fluorescence traces recorded from large-size neuronal population. PMID- 27375931 TI - Light distribution modulated diffuse reflectance spectroscopy. AB - Typically, a diffuse reflectance spectroscopy (DRS) system employing a continuous wave light source would need to acquire diffuse reflectances measured at multiple source-detector separations for determining the absorption and reduced scattering coefficients of turbid samples. This results in a multi-fiber probe structure and an indefinite probing depth. Here we present a novel DRS method that can utilize a few diffuse reflectances measured at one source-detector separation for recovering the optical properties of samples. The core of innovation is a liquid crystal (LC) cell whose scattering property can be modulated by the bias voltage. By placing the LC cell between the light source and the sample, the spatial distribution of light in the sample can be varied as the scattering property of the LC cell modulated by the bias voltage, and this would induce intensity variation of the collected diffuse reflectance. From a series of Monte Carlo simulations and phantom measurements, we found that this new light distribution modulated DRS (LDM DRS) system was capable of accurately recover the absorption and scattering coefficients of turbid samples and its probing depth only varied by less than 3% over the full bias voltage variation range. Our results suggest that this LDM DRS platform could be developed to various low-cost, efficient, and compact systems for in-vivo superficial tissue investigation. PMID- 27375932 TI - Characterisation of signal enhancements achieved when utilizing a photon diode in deep Raman spectroscopy of tissue. AB - We characterise the performance of a beam enhancing element ('photon diode') for use in deep Raman spectroscopy (DRS) of biological tissues. The optical component enhances the number of laser photons coupled into a tissue sample by returning escaping photons back into it at the illumination zone. The method is compatible with transmission Raman spectroscopy, a deep Raman spectroscopy concept, and its implementation leads to considerable enhancement of detected Raman photon rates. In the past, the enhancement concept was demonstrated with a variety of samples (pharmaceutical tablets, tissue, etc) but it was not systematically characterized with biological tissues. In this study, we investigate the enhancing properties of the photon diode in the transmission Raman geometry as a function of: a) the depth and b) the optical properties of tissue samples. Liquid tissue phantoms were employed to facilitate systematic variation of optical properties. These were chosen to mimic optical properties of human tissues, including breast and prostate. The obtained results evidence that a photon diode can enhance Raman signals of tissues by a maximum of * 2.4, although it can also decrease the signals created towards the back of samples that exhibit high scattering or absorption properties. PMID- 27375933 TI - Optically controlled release of DNA based on nonradiative relaxation process of quenchers. AB - Optically controlled release of a DNA strand based on a nonradiative relaxation process of black hole quenchers (BHQs), which are a sort of dark quenchers, is presented. BHQs act as efficient energy sources because they relax completely via a nonradiative process, i.e., without fluorescent emission-based energy losses. A DNA strand is modified with BHQs and the release of its complementary strand is controlled by excitation of the BHQs. Experimental results showed that up to 50% of the target strands were released, and these strands were capable of inducing subsequent reactions. The controlled release was localized on a substrate within an area of no more than 5 micrometers in diameter. PMID- 27375934 TI - Ultrathin lensed fiber-optic probe for optical coherence tomography. AB - We investigated and validated a novel method to develop ultrathin lensed fiber optic (LFO) probes for optical coherence tomography (OCT) imaging. We made the LFO probe by attaching a segment of no core fiber (NCF) to the distal end of a single mode fiber (SMF) and generating a curved surface at the tip of the NCF using the electric arc of a fusion splicer. The novel fabrication approach enabled us to control the length of the NCF and the radius of the fiber lens independently. By strategically choosing these two parameters, the LFO probe could achieve a broad range of working distance and depth of focus for different OCT applications. A probe with 125MUm diameter and lateral resolution up to 10MUm was demonstrated. The low-cost, disposable and robust LFO probe is expected to have great potential for interstitial OCT imaging. PMID- 27375935 TI - Astigmatic multifocus microscopy enables deep 3D super-resolved imaging. AB - We have developed a 3D super-resolution microscopy method that enables deep imaging in cells. This technique relies on the effective combination of multifocus microscopy and astigmatic 3D single-molecule localization microscopy. We describe the optical system and the fabrication process of its key element, the multifocus grating. Then, two strategies for localizing emitters with our imaging method are presented and compared with a previously described deep 3D localization algorithm. Finally, we demonstrate the performance of the method by imaging the nuclear envelope of eukaryotic cells reaching a depth of field of ~4um. PMID- 27375936 TI - Designed Er(3+)-singly doped NaYF4 with double excitation bands for simultaneous deep macroscopic and microscopic upconverting bioimaging. AB - Simultaneous deep macroscopic imaging and microscopic imaging is in urgent demand, but is challenging to achieve experimentally due to the lack of proper fluorescent probes. Herein, we have designed and successfully synthesized simplex Er(3+)-doped upconversion nanoparticles (UCNPs) with double excitation bands for simultaneous deep macroscopic and microscopic imaging. The material structure and the excitation wavelength of Er(3+)-singly doped UCNPs were further optimized to enhance the upconversion emission efficiency. After optimization, we found that NaYF4:30%Er(3+)@NaYF4:2%Er(3+) could simultaneously achieve efficient two-photon excitation (2PE) macroscopic tissue imaging and three-photon excitation (3PE) deep microscopic when excited by 808 nm continuous wave (CW) and 1480 nm CW lasers, respectively. In vitro cell imaging and in vivo imaging have also been implemented to demonstrate the feasibility and potential of the proposed simplex Er(3+)-doped UCNPs as bioprobe. PMID- 27375938 TI - Dual CARS and SHG image acquisition scheme that combines single central fiber and multimode fiber bundle to collect and differentiate backward and forward generated photons. AB - In coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) imaging, backward and forward generated photons exhibit different image patterns and thus capture salient intrinsic information of tissues from different perspectives. However, they are often mixed in collection using traditional image acquisition methods and thus are hard to interpret. We developed a multimodal scheme using a single central fiber and multimode fiber bundle to simultaneously collect and differentiate images formed by these two types of photons and evaluated the scheme in an endomicroscopy prototype. The ratio of these photons collected was calculated for the characterization of tissue regions with strong or weak epi-photon generation while different image patterns of these photons at different tissue depths were revealed. This scheme provides a new approach to extract and integrate information captured by backward and forward generated photons in dual CARS/SHG imaging synergistically for biomedical applications. PMID- 27375937 TI - Portable, parallel 9-wavelength near-infrared spectral tomography (NIRST) system for efficient characterization of breast cancer within the clinical oncology infusion suite. AB - A portable near-infrared spectral tomography (NIRST) system was developed with simultaneous frequency domain (FD) and continuous-wave (CW) optical measurements for efficient characterization of breast cancer in a clinical oncology setting. Simultaneous FD and CW recordings were implemented to speed up acquisition to 3 minutes for all 9 wavelengths, spanning a range from 661nm to 1064nm. An adjustable interface was designed to fit various breast sizes and shapes. Spatial images of oxy- and deoxy-hemoglobin, water, lipid, and scattering components were reconstructed using a 2D FEM approach. The system was tested on a group of 10 normal subjects, who were examined bilaterally and the recovered optical images were compared to radiographic breast density. Significantly higher total hemoglobin and water were estimated in the high density relative to low density groups. One patient with invasive ductal carcinoma was also examined and the cancer region was characterized as having a contrast ratio of 1.4 in total hemoglobin and 1.2 in water. PMID- 27375940 TI - Improved illumination system of laparoscopes using an aspherical lens array. AB - The current fiber-based illumination systems of laparoscopes are unable to uniformly illuminate a large enough area in abdomen due to the limited numerical aperture (NA) of the fiber bundle. Most energy is concentrated in a small region at the center of the illumination area. This limitation becomes problematic in laparoscopes which require capturing a wide field of view. In this paper, we propose an aspherical lens array which is used to direct the outgoing rays from the fiber bundle of laparoscope to produce a more uniformly illuminated, substantially larger field coverage than standalone fiber source. An intensity feedback method is developed to design the aspherical lens unit for extended non Lambertian sources, which is the key to the design of this lens array. By this method, the lens unit is obtained after only one iteration, and the lens array is constructed by Boolean operation. Then, the ray-tracing technique is used to verify the design. Further, the lens array is fabricated and experimental tests are performed. The results clearly show that the well-illuminated area is increased to about 0.107m(2) from 0.02m(2) (about 5x larger than a standard fiber illumination source). More details of the internal organs can be clearly observed under this improved illumination condition, which also reflects the significant improvement in the optical performance of the laparoscope. PMID- 27375939 TI - Single objective light-sheet microscopy for high-speed whole-cell 3D super resolution. AB - We have developed a method for performing light-sheet microscopy with a single high numerical aperture lens by integrating reflective side walls into a microfluidic chip. These 45 degrees side walls generate light-sheet illumination by reflecting a vertical light-sheet into the focal plane of the objective. Light sheet illumination of cells loaded in the channels increases image quality in diffraction limited imaging via reduction of out-of-focus background light. Single molecule super-resolution is also improved by the decreased background resulting in better localization precision and decreased photo-bleaching, leading to more accepted localizations overall and higher quality images. Moreover, 2D and 3D single molecule super-resolution data can be acquired faster by taking advantage of the increased illumination intensities as compared to wide field, in the focused light-sheet. PMID- 27375941 TI - Analysis of dengue infection based on Raman spectroscopy and support vector machine (SVM). AB - The current study presents the use of Raman spectroscopy combined with support vector machine (SVM) for the classification of dengue suspected human blood sera. Raman spectra for 84 clinically dengue suspected patients acquired from Holy Family Hospital, Rawalpindi, Pakistan, have been used in this study.The spectral differences between dengue positive and normal sera have been exploited by using effective machine learning techniques. In this regard, SVM models built on the basis of three different kernel functions including Gaussian radial basis function (RBF), polynomial function and linear functionhave been employed to classify the human blood sera based on features obtained from Raman Spectra.The classification model have been evaluated with the 10-fold cross validation method. In the present study, the best performance has been achieved for the polynomial kernel of order 1. A diagnostic accuracy of about 85% with the precision of 90%, sensitivity of 73% and specificity of 93% has been achieved under these conditions. PMID- 27375942 TI - Line-scanning fiber bundle endomicroscopy with a virtual detector slit. AB - Coherent fiber bundles can be used to relay the image plane from the distal tip of an endomicroscope to an external confocal microscopy system. The frame rate is therefore determined by the speed of the microscope's laser scanning system which, at 10-20 Hz, may be undesirably low for in vivo clinical applications. Line-scanning allows an increase in the frame rate by an order of magnitude in exchange for some loss of optical sectioning, but the width of the detector slit cannot easily be adapted to suit different imaging conditions. The rolling shutter of a CMOS camera can be used as a virtual detector slit for a bench-top line-scanning confocal microscope, and here we extend this idea to endomicroscopy. By synchronizing the camera rolling shutter with a scanning laser line we achieve confocal imaging with an electronically variable detector slit. This architecture allows us to acquire every other frame with the detector slit offset by a known distance, and we show that subtracting this second image leads to improved optical sectioning. PMID- 27375943 TI - In vivo assessment of optical properties of basal cell carcinoma and differentiation of BCC subtypes by high-definition optical coherence tomography. AB - High-definition optical coherence tomography (HD-OCT) features of basal cell carcinoma (BCC) have recently been defined. We assessed in vivo optical properties (IV-OP) of BCC, by HD-OCT. Moreover their critical values for BCC subtype differentiation were determined. The technique of semi-log plot whereby an exponential function becomes linear has been implemented on HD-OCT signals. The relative attenuation factor (uraf ) at different skin layers could be assessed.. IV-OP of superficial BCC with high diagnostic accuracy (DA) and high negative predictive values (NPV) were (i) decreased uraf in lower part of epidermis and (ii) increased epidermal thickness (E-T). IV-OP of nodular BCC with good to high DA and NPV were (i) less negative uraf in papillary dermis compared to normal adjacent skin and (ii) significantly decreased E-T and papillary dermal thickness (PD-T). In infiltrative BCC (i) high uraf in reticular dermis compared to normal adjacent skin and (ii) presence of peaks and falls in reticular dermis had good DA and high NPV. HD-OCT seems to enable the combination of in vivo morphological analysis of cellular and 3-D micro-architectural structures with IV OP analysis of BCC. This permits BCC sub-differentiation with higher accuracy than in vivo HD-OCT analysis of morphology alone. PMID- 27375944 TI - Simultaneous multicolor imaging of wide-field epi-fluorescence microscopy with four-bucket detection. AB - We demonstrate simultaneous imaging of multiple fluorophores using wide-field epi fluorescence microscopy with a monochrome camera. The intensities of the three lasers are modulated by a sinusoidal waveform in order to excite each fluorophore with the same modulation frequency and a different time-delay. Then, the modulated fluorescence emissions are simultaneously detected by a camera operating at four times the excitation frequency. We show that two different fluorescence beads having crosstalk can be clearly separated using digital processing based on the phase information. In addition, multiple organelles within multi-stained single cells are shown with the phase mapping method, demonstrating an improved dynamic range and contrast compared to the conventional fluorescence image. These findings suggest that wide-field epi-fluorescence microscopy with four-bucket detection could be utilized for high-contrast multicolor imaging applications such as drug delivery and fluorescence in situ hybridization. PMID- 27375946 TI - Quantitative and simultaneous non-invasive measurement of skin hydration and sebum levels. AB - We report a method on quantitative and simultaneous non-contact in-vivo hydration and sebum measurements of the skin using an infrared optical spectroscopic set up. The method utilizes differential detection with three wavelengths 1720, 1750, and 1770 nm, corresponding to the lipid vibrational bands that lay "in between" the prominent water absorption bands. We have used an emulsifier containing hydro and lipophilic components to mix water and sebum in various volume fractions which was applied to the skin to mimic different oily-dry skin conditions. We also measured the skin sebum and hydration values on the forehead under natural conditions and its variations to external stimuli. Good agreement was found between our experimental results and reference values measured using conventional biophysical methods such as Corneometer and Sebumeter. PMID- 27375945 TI - Applicability, usability, and limitations of murine embryonic imaging with optical coherence tomography and optical projection tomography. AB - We present an analysis of imaging murine embryos at various embryonic developmental stages (embryonic day 9.5, 11.5, and 13.5) by optical coherence tomography (OCT) and optical projection tomography (OPT). We demonstrate that while OCT was capable of rapid high-resolution live 3D imaging, its limited penetration depth prevented visualization of deeper structures, particularly in later stage embryos. In contrast, OPT was able to image the whole embryos, but could not be used in vivo because the embryos must be fixed and cleared. Moreover, the fixation process significantly altered the embryo morphology, which was quantified by the volume of the eye-globes before and after fixation. All of these factors should be weighed when determining which imaging modality one should use to achieve particular goals of a study. PMID- 27375947 TI - Detection of retinal blood vessel changes in multiple sclerosis with optical coherence tomography. AB - Although retinal vasculitis is common in multiple sclerosis (MS), it is not known if MS is associated with quantitative abnormalities in retinal blood vessels (BVs). Optical coherence tomography (OCT) is suitable for examining the integrity of the anterior visual pathways in MS. In this paper we have compared the size and number of retinal blood vessels in patients with MS, with and without a history of optic neuritis (ON), and control subjects from the cross-sectional retinal images from OCT. Blood vessel diameter (BVD), blood vessel number (BVN), and retinal nerve fiber layer thickness (RNFLT) were extracted from OCT images collected from around the optic nerves of 129 eyes (24 control, 24 MS + ON, 81 MS ON) of 71 subjects. Associations between blood vessel metrics, MS diagnosis, MS disability, ON, and RNFLT were evaluated using generalized estimating equation (GEE) models. MS eyes had a lower total BVD and BVN than control eyes. The effect was more pronounced with increased MS disability, and persisted in multivariate models adjusting for RNFLT and ON history. Twenty-nine percent (29%) of MS subjects had fewer retinal blood vessels than all control subjects. MS diagnosis, disability, and ON history were not associated with average blood vessel size. The relationship between MS and lower total BVD/BVN is not accounted for by RNFLT or ON. Further study is needed to determine the relationship between OCT blood vessel metrics and qualitative retinal blood vessel abnormalities in MS. PMID- 27375948 TI - Dynamic absorption and scattering of water and hydrogel during high-repetition rate (>100 MHz) burst-mode ultrafast-pulse laser ablation. AB - High-repetition-rate burst-mode ultrafast-laser ablation and disruption of biological tissues depends on interaction of each pulse with the sample, but under those particular conditions which persist from previous pulses. This work characterizes and compares the dynamics of absorption and scattering of a 133-MHz repetition-rate, burst-mode ultrafast-pulse laser, in agar hydrogel targets and distilled water. The differences in energy partition are quantified, pulse-by pulse, using a time-resolving integrating-sphere-based device. These measurements reveal that high-repetition-rate burst-mode ultrafast-laser ablation is a highly dynamical process affected by the persistence of ionization, dissipation of plasma plume, neutral material flow, tissue tensile strength, and the hydrodynamic oscillation of cavitation bubbles. PMID- 27375949 TI - Novel l 2,1-norm optimization method for fluorescence molecular tomography reconstruction. AB - Fluorescence molecular tomography (FMT) is a promising tomographic method in preclinical research, which enables noninvasive real-time three-dimensional (3-D) visualization for in vivo studies. The ill-posedness of the FMT reconstruction problem is one of the many challenges in the studies of FMT. In this paper, we propose a l 2,1-norm optimization method using a priori information, mainly the structured sparsity of the fluorescent regions for FMT reconstruction. Compared to standard sparsity methods, the structured sparsity methods are often superior in reconstruction accuracy since the structured sparsity utilizes correlations or structures of the reconstructed image. To solve the problem effectively, the Nesterov's method was used to accelerate the computation. To evaluate the performance of the proposed l 2,1-norm method, numerical phantom experiments and in vivo mouse experiments are conducted. The results show that the proposed method not only achieves accurate and desirable fluorescent source reconstruction, but also demonstrates enhanced robustness to noise. PMID- 27375950 TI - Erratum: Particle streak velocimetry-optical coherence tomography: a novel method for multidimensional imaging of microscale fluid flows: erratum. AB - [This corrects the article on p. 1590 in vol. 7.]. PMID- 27375952 TI - Angle correction for small animal tumor imaging with spatial frequency domain imaging (SFDI). AB - Spatial frequency domain imaging (SFDI) is a widefield imaging technique that allows for the quantitative extraction of tissue optical properties. SFDI is currently being explored for small animal tumor imaging, but severe imaging artifacts occur for highly curved surfaces (e.g. the tumor edge). We propose a modified Lambertian angle correction, adapted from the Minnaert correction method for satellite imagery, to account for tissue surface angles up to 75 degrees . The method was tested in a hemisphere phantom study as well as a small animal tumor model. The proposed method reduced ua and us' extraction errors by an average of 64% and 16% respectively compared to performing no angle correction, and provided more physiologically agreeable optical property and chromophore values on tumors. PMID- 27375951 TI - Combination of an optical parametric oscillator and quantum-dots 655 to improve imaging depth of vasculature by intravital multicolor two-photon microscopy. AB - Simultaneous imaging of different cell types and structures in the mouse central nervous system (CNS) by intravital two-photon microscopy requires the characterization of fluorophores and advances in approaches to visualize them. We describe the use of a two-photon infrared illumination generated by an optical parametric oscillator (OPO) on quantum-dots 655 (QD655) nanocrystals to improve resolution of the vasculature deeper in the mouse brain both in healthy and pathological conditions. Moreover, QD655 signal can be unmixed from the DsRed2, CFP, EGFP and EYFP fluorescent proteins, which enhances the panel of multi parametric correlative investigations both in the cortex and the spinal cord. PMID- 27375953 TI - Cell morphology-based classification of red blood cells using holographic imaging informatics. AB - We present methods that automatically select a linear or nonlinear classifier for red blood cell (RBC) classification by analyzing the equality of the covariance matrices in Gabor-filtered holographic images. First, the phase images of the RBCs are numerically reconstructed from their holograms, which are recorded using off-axis digital holographic microscopy (DHM). Second, each RBC is segmented using a marker-controlled watershed transform algorithm and the inner part of the RBC is identified and analyzed. Third, the Gabor wavelet transform is applied to the segmented cells to extract a series of features, which then undergo a multivariate statistical test to evaluate the equality of the covariance matrices of the different shapes of the RBCs using selected features. When these covariance matrices are not equal, a nonlinear classification scheme based on quadratic functions is applied; otherwise, a linear classification is applied. We used the stomatocyte, discocyte, and echinocyte RBC for classifier training and testing. Simulation results demonstrated that 10 of the 14 RBC features are useful in RBC classification. Experimental results also revealed that the covariance matrices of the three main RBC groups are not equal and that a nonlinear classification method has a much lower misclassification rate. The proposed automated RBC classification method has the potential for use in drug testing and the diagnosis of RBC-related diseases. PMID- 27375954 TI - Fluorescence properties of several chemotherapy drugs: doxorubicin, paclitaxel and bleomycin. AB - Several chemo-drugs act as the biocompatible fluorophores. Here, the laser induced fluorescence (LIF) properties of doxorubicin, paclitaxel and bleomycin are investigated. The absorption lines mostly lie over UV range according to the UV-VIS spectra. Therefore, a single XeCl laser provokes the desired transitions of the chemo-drugs of interest at 308 nm. It is shown that LIF spectra are strongly dependent on the fluorophore concentration giving rise to the sensible red shift. This happens when large overlapping area appears between absorption and emission spectra accordingly. The red shift is taken into account as a characteristic parameter of a certain chemo-drug. The fluorescence extinction (alpha) and self-quenching (k) coefficients are determined based on the best fitting of the adopted Lambert-Beer equation over experimental data. The quantum yield of each chemo-drug is also measured using the linearity of the absorption and emission rates. PMID- 27375955 TI - SERS-active Au/SiO2 clouds in powder for rapid ex vivo breast adenocarcinoma diagnosis. AB - In the present work, we report a dry-based application technique of Au/SiO2 clouds in powder for rapid ex vivo adenocarcinoma diagnosis through surface enhanced Raman scattering (SERS); using low laser power and an integration time of one second. Several characteristic Raman peaks frequently used for the diagnosis of breast adenocarcinoma in the range of the amide III are successfully enhanced by breading the tissue with Au/SiO2 powder. The SERS activity of these Au/SiO2 powders is attributed to their rapid rehydration upon contact with the wet tissues, which promotes the formation of gold nanoparticle aggregates. The propensity of the Au/SiO2 cloud structures to adsorb biomolecules in the vicinity of the gold nanoparticle clusters promotes the necessary conditions for SERS detection. In addition, electron microscopy, together with elemental analysis, have been used to confirm the structure of the new Au/SiO2 cloud material and to investigate its distribution in breast tissues. PMID- 27375956 TI - Infrared spectroscopic imaging detects chemical modifications in liver fibrosis due to diabetes and disease. AB - The importance of stroma as a rich diagnostic region in tissue biopsies is growing as there is an increasing understanding that disease processes in multiple organs can affect the composition of adjacent connective tissue regions. This may be especially true in the liver, since this organ's central metabolic role exposes it to multiple disease processes. We use quantum cascade laser infrared spectroscopic imaging to study changes in the chemical status of hepatocytes and fibrotic regions of liver tissue that result from the progression of liver cirrhosis to hepatocellular carcinoma and the potentially confounding effects of diabetes mellitus. PMID- 27366584 TI - If Numbers Can Speak, Who Listens? Creating Engagement and Learning for Effective Uptake of DRR Investment in Developing Countries. AB - INTRODUCTION: With a renewed emphasis on evidence-based risk sensitive investment promoted under the Sendai Framework for Disaster Risk Reduction 2015-2030, technical demands for analytical tools such as probabilistic cost-benefit analysis (CBA) will likely increase in the foreseeable future. This begs a number of pragmatic questions such as whether or not sophisticated quantitative appraisal tools are effective in raising policy awareness and what alternatives are available. METHOD: This article briefly reviews current practices of analytical tools such as probabilistic cost-benefit analysis and identifies issues associated with its applications in small scale community based DRR interventions. RESULTS: The article illustrate that while best scientific knowledge should inform policy and practice in principle, it should not create an unrealistic expectation that the state-of-the art methods must be used in all cases, especially for small scale DRR interventions in developing countries, where data and resource limitations and uncertainty are high, and complex interaction and feedback may exist between DRR investment, community response and longer-term development outcome. DISCUSSION: Alternative and more participatory approaches for DRR appraisals are suggested which includes participatory serious games that are increasingly being used to raise awareness and identify pragmatic strategies for change that are needed to bring about successful uptake of DRR investment and implementation of DRR mainstreaming. PMID- 27375959 TI - Short-Term Change in Couples' Conflict Following a Transition to Parenthood Intervention. AB - Conflict among couples was examined following a transition to parenthood intervention to determine both short-term efficacy of the program and elucidate the process of change postintervention. A randomized clinical trial design was used to examine conflict in couples who participated in a transition to parenthood psycho-educational workshop compared with controls. The beginnings of improved communication in conflict were evident at 3 months postbirth through decreased husband contempt and increased husband positive affect during conflict in a sample that demonstrated more substantial improvement at 1 year postintervention. Increases in husband positive affect in the workshop group at 3 months postbirth predicted more positive and less negative wife affect during conflict at 1 year postbirth. Results suggest that some indicators of intervention efficacy were evident, postintervention change can be gradual, husbands may be more receptive to implementing change shortly after birth, and early changes can be associated with later positive outcomes. Findings have implications for preparing couples for the gradual and complex nature of change associated with intervention. PMID- 27375958 TI - Pilin Vaccination Stimulates Weak Antibody Responses and Provides No Protection in a C57Bl/6 Murine Model of Acute Clostridium difficile Infection. AB - Clostridium difficile is the leading cause of nosocomial infections in the United States, adding billions of dollars per year to health care costs. A vaccine targeted against the bacterium would be extremely beneficial in decreasing the morbidity and mortality caused by C. difficile-associated disease; a vaccine directed against a colonization factor would hinder the spread of the bacterium as well as prevent disease. Type IV pili (T4Ps) are extracellular appendages composed of protein monomers called pilins. They are involved in adhesion and colonization in a wide variety of bacteria and archaea, and are putative colonization factors in C. difficile. We hypothesized that vaccinating mice with pilins would lead to generation of anti-pilin antibodies, and would protect against C. difficile challenge. We found that immunizing C57Bl/6 mice with various pilins, whether combined or as individual proteins, led to low anti-pilin antibody titers and no protection upon C. difficile challenge. Passive transfer of anti-pilin antibodies led to high serum anti-pilin IgG titers, but to undetectable fecal anti-pilin IgG titers and did not protect against challenge. The low antibody titers observed in these experiments may be due to the particular strain of mice used. Further experiments, possibly with a different animal model of C. difficile infection, are needed to determine if an anti-T4P vaccine would be protective against C. difficile infection. PMID- 27375961 TI - Late-Onset Psychogenic Chronic Phonic-Tics. AB - BACKGROUND: Tics beginning in late adulthood often have an identifiable etiology. Psychogenic tics with onset around 60 years of age are rarely described in the literature. CASE REPORT: A 67-year-old female had experienced phonic tics for 8 years. Episodes occurred without premonitory sensations and precipitant factors, and she could not suppress them. She had no history of childhood tic disorder, and secondary causes of tics were excluded. She was diagnosed with psychogenic tics and treated with quetiapine with mild improvement. DISCUSSION: When physicians are faced with no identifiable cause of tics combined with certain clinical clues, a psychogenic disorder must be suspected. PMID- 27375960 TI - Cerebellar Dysfunction and Ataxia in Patients with Epilepsy: Coincidence, Consequence, or Cause? AB - Basic epilepsy teachings assert that seizures arise from the cerebral cortex, glossing over infratentorial structures such as the cerebellum that are believed to modulate rather than generate seizures. Nonetheless, ataxia and other clinical findings in epileptic patients are slowly but inevitably drawing attention to this neural node. Tracing the evolution of this line of inquiry from the observed coincidence of cerebellar atrophy and cerebellar dysfunction (most apparently manifested as ataxia) in epilepsy to their close association, this review considers converging clinical, physiological, histological, and neuroimaging evidence that support incorporating the cerebellum into epilepsy pathology. We examine reports of still controversial cerebellar epilepsy, studies of cerebellar stimulation alleviating paroxysmal epileptic activity, studies and case reports of cerebellar lesions directly associated with seizures, and conditions in which ataxia is accompanied by epileptic seizures. Finally, the review substantiates the role of this complex brain structure in epilepsy whether by coincidence, as a consequence of deleterious cortical epileptic activity or antiepileptic drugs, or the very cause of the disease. PMID- 27375962 TI - Wearable Sensor System Powered by a Biofuel Cell for Detection of Lactate Levels in Sweat. AB - An NAD+-dependent enzymatic sensor with biofuel cell power source system for non invasive monitoring of lactate in sweat was designed, developed, and tested. The sensor component, based on lactate dehydrogenase, showed linear current response with increasing lactate concentrations with limits of detection from 5 to 100 mM lactate and sensitivity of 0.2 uA.mM-1 in the presence of target analyte. In addition to the sensor patch a power source was also designed, developed and tested. The power source was a biofuel cell designed to oxidize glucose via glucose oxidase. The biofuel cell showed excellent performance, achieving over 80 mA at 0.4 V (16 mW) in a footprint of 3.5 * 3.5 * 0.7 cm. Furthermore, in order to couple the sensor to the power source, system electronic components were designed and fabricated. These consisted of an energy harvester (EH) and a micropotentiostat (MP). The EH was employed for harvesting power provided by the biofuel cell as well as up-converting the voltage to 3.0 V needed for the operation of the MP. The sensor was attached to MP for chronoamperometric detection of lactate. The Sensor Patch System was demonstrated under laboratory conditions. PMID- 27375964 TI - Using homogenization, sonication and thermo-sonication to inactivate fungi. AB - Ultrasound (US), Thermo-sonication (TS) and High Pressure Homogenization (HPH) were studied as tools to inactivate the spores of Penicillium spp. and Mucor spp. inoculated in distilled water. For US, the power ranged from 40% to 100%, pulse from 2 to 10 s, and duration of the treatment from 2 to 10 min. TS was performed combining US (40-80% of power, for 8 min and pulse of 2 s) with a thermal treatment (50, 55 and 60 degrees C at 4, 8 and 12 min). Homogenization was done at 30-150 MPa for 1, 2 and 3 times. Power was the most important factors to determine the antifungal effect of US and TS towards the conidia of Penicillium spp.; on the other hand, in US treatments Mucor spp. was also affected by pulse and time. HPH exerted a significant antifungal effect only if the highest pressures were applied for 2-3 times. PMID- 27375963 TI - Stressful life events moderate the relationship between genes and biased attention to emotional faces in youth. AB - Attention bias to emotion may be an intermediate trait for stress-reactive psychopathology associated with biologically plausible candidate genes, yet the precise direction of effects within the youth literature remains unclear. The present study investigated whether stressful life events (SLEs) moderate the link between genetic risk (5-HTTLPR and COMT) and attention bias to emotion among youth (n= 467). Analyses revealed a differential effect of gene. Among youth who had experienced more recent SLEs, those homozygous for the low expressing allele of 5-HTTLPR (S/S) demonstrated preferential attention toward negative emotional expressions, whereas youth homozygous for the high expressing COMT genotype (Val/Val) showed attentional avoidance of positive facial expressions. No interaction between 5-HTTLPR and COMT was found. These findings highlight the importance of investigating stress as a moderator within the intermediate trait literature and suggest that biologically plausible candidate genes may have a differential effect in the pathway to psychological disorders. PMID- 27375966 TI - Protein-RNA linkage and posttranslational modifications of feline calicivirus and murine norovirus VPg proteins. AB - Members of the Caliciviridae family of positive sense RNA viruses cause a wide range of diseases in both humans and animals. The detailed characterization of the calicivirus life cycle had been hampered due to the lack of robust cell culture systems and experimental tools for many of the members of the family. However, a number of caliciviruses replicate efficiently in cell culture and have robust reverse genetics systems available, most notably feline calicivirus (FCV) and murine norovirus (MNV). These are therefore widely used as representative members with which to examine the mechanistic details of calicivirus genome translation and replication. The replication of the calicivirus RNA genome occurs via a double-stranded RNA intermediate that is then used as a template for the production of new positive sense viral RNA, which is covalently linked to the virus-encoded protein VPg. The covalent linkage to VPg occurs during genome replication via the nucleotidylylation activity of the viral RNA-dependent RNA polymerase. Using FCV and MNV, we used mass spectrometry-based approach to identify the specific amino acid linked to the 5' end of the viral nucleic acid. We observed that both VPg proteins are covalently linked to guanosine diphosphate (GDP) moieties via tyrosine positions 24 and 26 for FCV and MNV respectively. These data fit with previous observations indicating that mutations introduced into these specific amino acids are deleterious for viral replication and fail to produce infectious virus. In addition, we also detected serine phosphorylation sites within the FCV VPg protein with positions 80 and 107 found consistently phosphorylated on VPg-linked viral RNA isolated from infected cells. This work provides the first direct experimental characterization of the linkage of infectious calicivirus viral RNA to the VPg protein and highlights that post translational modifications of VPg may also occur during the viral life cycle. PMID- 27375965 TI - Complete plastid genome sequence of Primula sinensis (Primulaceae): structure comparison, sequence variation and evidence for accD transfer to nucleus. AB - Species-rich genus Primula L. is a typical plant group with which to understand genetic variance between species in different levels of relationships. Chloroplast genome sequences are used to be the information resource for quantifying this difference and reconstructing evolutionary history. In this study, we reported the complete chloroplast genome sequence of Primula sinensis and compared it with other related species. This genome of chloroplast showed a typical circular quadripartite structure with 150,859 bp in sequence length consisting of 37.2% GC base. Two inverted repeated regions (25,535 bp) were separated by a large single-copy region (82,064 bp) and a small single-copy region (17,725 bp). The genome consists of 112 genes, including 78 protein-coding genes, 30 tRNA genes and four rRNA genes. Among them, seven coding genes, seven tRNA genes and four rRNA genes have two copies due to their locations in the IR regions. The accD and infA genes lacking intact open reading frames (ORF) were identified as pseudogenes. SSR and sequence variation analyses were also performed on the plastome of Primula sinensis, comparing with another available plastome of P. poissonii. The four most variable regions, rpl36-rps8, rps16-trnQ, trnH-psbA and ndhC-trnV, were identified. Phylogenetic relationship estimates using three sub-datasets extracted from a matrix of 57 protein-coding gene sequences showed the identical result that was consistent with previous studies. A transcript found from P. sinensis transcriptome showed a high similarity to plastid accD functional region and was identified as a putative plastid transit peptide at the N-terminal region. The result strongly suggested that plastid accD has been functionally transferred to the nucleus in P. sinensis. PMID- 27375967 TI - Modulation of the behavioral and electrical responses to the repellent DEET elicited by the pre-exposure to the same compound in Blattella germanica. AB - Insects under different stimuli from the environment modify behavioural responses due to changes in the sensitivity of neurons at the peripheral and/or at the central level of the nervous system. This phenomenon is called neuronal plasticity, and sensory adaptation is an example of it. An insect repellent is a chemical that produces oriented movements of the insects away from its source. In this work we studied the modulation of the behavioural and electrical response to the repellent N, N-diethyl-3-methylbenzamide (DEET) in males of the German cockroach B. germanica produced by previous exposure to the same repellent. Methods. We determined repellency using a circular arena, one half of which was treated with DEET. The time spent by insects in each half of the arena was measured, and a repellency coefficient (RC) was calculated. The RCs of pre exposed and non-pre-exposed insects were compared. To determine a possible role of nitric oxide in the modulation of the response to DEET after pre-exposure, the nitric oxide donor S-nitroso-acetyl-cysteine (SNAC) was applied on cockroaches' antennae. The electrical activity of the cockroaches' antennae in response to DEET was recorded using electroantennogram (EAG) technique. The response to DEET was recorded also after a long stimulation with the same repellent, and after topical application of SNAC and dbcGMP (a cGMP analogue) on the antennae. Results. We found that previous exposure of B. germanica males to the repellent DEET produced an increase of the repellency at the behavioural level, measured as RC. A possible role of nitric oxide (NO) in the transduction pathway of this phenomenon is suggested, since treatment of the cockroaches with the NO donor SNAC also produced an increase of the repellency elicited by DEET. On the other hand, the response of the cockroaches' antennae exposed to DEET was determined electrophysiologically. The electrical activity in response to DEET decreased when the insects' antennae were stimulated with a long pulse of the repellent. The activity of the antennae was restored after 10 min. Treatment of the antennae either with SNAC or dbGMPc also produced a decrease in the response of the antennae to the repellent. Discussion.The previous exposure to a chemical stimulus can modify the behaviour associated to the same stimulus, increasing or decreasing the behavioural response. In the case of DEET we found that pre exposure increased DEET repellency in male cockroaches. We also found NO involvement in a similar phenomenon. On the other hand, the test showed that DEET is perceived by insects' antennae as an odour. A long exposure of the antennae to DEET caused a transient decrease in the response of the antennae to the same compound. The same effect was achieved by treating the antennae with SNAC or dbcGMP, suggesting the involvement of the NO/cGMP system in the transduction pathway of the sensory adaptation phenomenon elicited by an odour in this species. PMID- 27375968 TI - Design and validation of a next generation sequencing assay for hereditary BRCA1 and BRCA2 mutation testing. AB - Hereditary breast and ovarian cancer syndrome, caused by a germline pathogenic variant in the BRCA1 or BRCA2 (BRCA1/2) genes, is characterized by an increased risk for breast, ovarian, pancreatic and other cancers. Identification of those who have a BRCA1/2 mutation is important so that they can take advantage of genetic counseling, screening, and potentially life-saving prevention strategies. We describe the design and analytic validation of the Counsyl Inherited Cancer Screen, a next-generation-sequencing-based test to detect pathogenic variation in the BRCA1 and BRCA2 genes. We demonstrate that the test is capable of detecting single-nucleotide variants (SNVs), short insertions and deletions (indels), and copy-number variants (CNVs, also known as large rearrangements) with zero errors over a 114-sample validation set consisting of samples from cell lines and deidentified patient samples, including 36 samples with BRCA1/2pathogenic germline mutations. PMID- 27375969 TI - Shapes of leaves with parallel venation. Modelling of the Epipactis sp. (Orchidaceae) leaves with the help of a system of coupled elastic beams. AB - Static properties of leaves with parallel venation, with particular emphasis on the genus EpipactisZinn, 1757 (Orchidaceae, Neottieae) have been modelled with coupled quasi-parallel elastic "beams." The non-linear theory of strongly bended beams have been employed. The resulting boundary-value problem has been solved numerically with the help of the finite-difference method. Possible dislocations resulting in additional Dirac-delta like forces have been take into account. Morphological similarity of the model and real leaves has been obtained. In particular, the concentrated forces have been shown to cause undulation in the leaves. PMID- 27375970 TI - Monitoring coastal pollution associated with the largest oil refinery complex of Venezuela. AB - This study evaluated pollution levels in water and sediments of Peninsula de Paraguana and related these levels with benthic macrofauna along a coastal area where the largest Venezuelan oil refineries have operated over the past 60 years. For this, the concentration of heavy metals, of hydrocarbon compounds and the community structure of the macrobenthos were examined at 20 sites distributed along 40 km of coastline for six consecutive years, which included windy and calm seasons. The spatial variability of organic and inorganic compounds showed considerably high coastal pollution along the study area, across both years and seasons. The southern sites, closest to the refineries, had consistently higher concentrations of heavy metals and organic compounds in water and sediments when compared to those in the north. The benthic community was dominated by polychaetes at all sites, seasons and years, and their abundance and distribution were significantly correlated with physical and chemical characteristics of the sediments. Sites close to the oil refineries were consistently dominated by families known to tolerate xenobiotics, such as Capitellidae and Spionidae. The results from this study highlight the importance of continuing long-term environmental monitoring programs to assess the impact of effluent discharge and spill events from the oil refineries that operate in the western coast of Paraguana, Venezuela. PMID- 27375971 TI - Collecting reliable clades using the Greedy Strict Consensus Merger. AB - Supertree methods combine a set of phylogenetic trees into a single supertree. Similar to supermatrix methods, these methods provide a way to reconstruct larger parts of the Tree of Life, potentially evading the computational complexity of phylogenetic inference methods such as maximum likelihood. The supertree problem can be formalized in different ways, to cope with contradictory information in the input. Many supertree methods have been developed. Some of them solve NP-hard optimization problems like the well-known Matrix Representation with Parsimony, while others have polynomial worst-case running time but work in a greedy fashion (FlipCut). Both can profit from a set of clades that are already known to be part of the supertree. The Superfine approach shows how the Greedy Strict Consensus Merger (GSCM) can be used as preprocessing to find these clades. We introduce different scoring functions for the GSCM, a randomization, as well as a combination thereof to improve the GSCM to find more clades. This helps, in turn, to improve the resolution of the GSCM supertree. We find this modifications to increase the number of true positive clades by 18% compared to the currently used Overlap scoring. PMID- 27375972 TI - Reciproc vs. hand instrumentation in dental practice: a study in routine care. AB - Background. Little is known about the clinical impact of new root canal preparation systems in general dental practice under routine care conditions. Therefore, we compared hand instrumentation (H) with Reciproc (R) (VDW, Munich, Germany) preparation. The outcomes were endodontic related pain and oral health related quality of life (OHRQoL), evaluation of the procedures by the patients and the strain felt by the dentists during root canal therapy. Methods. Six dentists participated in the trial as practitioner-investigators. In the first phase of the trial they prepared root canals with H and in the second phase with R. The patients documented their pain felt with a visual analogue scale (VAS 100) and OHRQoL with the German short version of the oral health impact profile (OHIP G-14) before treatment and before the completion of therapy and answered questions about how they experienced the treatment. The dentists documented their physical strain during treatment. Results. A total of 137 patients were included in the evaluation. 66 patients were treated with H, 71 with R. Pain reduction was 32.6 (SD 32.9) VAS (H) vs. 29.4 (SD 26.9) VAS (R) (p = 0.550), and the improvement of the OHIP-14 score was 5.5 (SD 9.2) (H) vs. 6.7 (SD 7.4) (R) (p = 0.383). There were no statistical differences in both groups. Significantly fewer patients felt stressed by the duration of treatment with R as with H (p = 0.018). Significantly more dentists reported that their general physical strain and the strain on their fingers were less severe with R than with H (p = 0.013 and p < 0.001). Discussion. H as well as R effectively reduced endodontic related pain and OHRQoL without statistical differences. R has advantages in terms of how patients experience the treatment and regarding the physical strain felt by the dentists. PMID- 27375973 TI - A novel baculovirus-derived promoter with high activity in the baculovirus expression system. AB - The baculovirus expression vector system (BEVS) has been widely used to produce a large number of recombinant proteins, and is becoming one of the most powerful, robust, and cost-effective systems for the production of eukaryotic proteins. Nevertheless, as in any other protein expression system, it is important to improve the production capabilities of this vector. The orf46 viral gene was identified among the most highly abundant sequences in the transcriptome of Spodoptera exigua larvae infected with its native baculovirus, the S. exigua multiple nucleopolyhedrovirus (SeMNPV). Different sequences upstream of the orf46 gene were cloned, and their promoter activities were tested by the expression of the GFP reporter gene using the Autographa californica nucleopolyhedrovirus (AcMNPV) vector system in different insect cell lines (Sf21, Se301, and Hi5) and in larvae from S. exigua and Trichoplusia ni. The strongest promoter activity was defined by a 120 nt sequence upstream of the ATG start codon for the orf46 gene. On average, GFP expression under this new promoter was more than two fold higher than the expression obtained with the standard polyhedrin (polh) promoter. Additionally, the orf46 promoter was also tested in combination with the polh promoter, revealing an additive effect over the polh promoter activity. In conclusion, this new characterized promoter represents an excellent alternative to the most commonly used baculovirus promoters for the efficient expression of recombinant proteins using the BEVS. PMID- 27375974 TI - To Screen or not to Screen: Low Dose Computed Tomography in Comparison to Chest Radiography or Usual Care in Reducing Morbidity and Mortality from Lung Cancer. AB - Lung cancer has the highest mortality rate of all cancers. This paper seeks to address the question: Can the mortality of lung cancer be decreased by screening with low-dose computerized tomography (LDCT) in higher risk patients compared to chest X-rays (CXR) or regular patient care? Currently, CXR screening is recommended for certain high-risk patients. Several recent trials have examined the effectiveness of LDCT versus chest radiography or usual care as a control. These trials include National Lung Screening Trial (NLST), Detection And screening of early lung cancer with Novel imaging TEchnology (DANTE), Lung Screening Study (LSS), Depiscan, Italian Lung (ITALUNG), and Dutch-Belgian Randomized Lung Cancer Screening Trial (Dutch acronym: NELSON study). NLST, the largest trial (n=53, 454), demonstrated a decrease in mortality from lung cancer in the LDCT group (RRR=20%, P=0.004). LSS demonstrated a greater sensitivity in detecting both early stage and any stage of lung cancer in comparison to traditional CXR. Although the DANTE trial yielded data consistent with findings in LSS, it also showed that via LDCT screening a greater proportion of patients were placed under unnecessary surgical procedures. The Depiscan trial yielded a high nodule detection rate at the cost of a high false-positive rate compared to CXR screening. The ITALUNG and NELSON trials demonstrated the early detection capabilities of LDCT for lung cancers compared to usual care without surveillance imaging. False-positive findings with unnecessary workup, intervention, and radiation exposure remain significant concerns for routine LDCT screening. However, current data suggests LDCT may provide a highly sensitive and specific means for detecting lung cancers and reducing mortality. PMID- 27375976 TI - Cheap talk communication with dynamic information searching. AB - We build an agent-based cheap talk communication model with dynamic information searching behavior. In this model, agent communicates with its neighbors freely to get true or false information. Moreover, the uninformed receivers has ability to break up one link of his neighbor who is considered as a dishonest sender and searches for a new neighbor in the market. We study the impacts of the accuracy of information, the number of neighbors and the percentage of relinking neighbors on the information identification of uninformed receivers. The results suggest that the effect of the accuracy of information and the number of neighbors on information identification is linear, but the effect of the percentage of relinking neighbors presents a first increasing and then decreasing trend. PMID- 27375975 TI - Keeping It in Three Dimensions: Measuring the Development of Mental Rotation in Children with the Rotated Colour Cube Test (RCCT). AB - This study introduces the new Rotated Colour Cube Test (RCCT) as a measure of object identification and mental rotation using single 3D colour cube images in a matching-to-sample procedure. One hundred 7- to 11-year-old children were tested with aligned or rotated cube models, distracters and targets. While different orientations of distracters made the RCCT more difficult, different colours of distracters had the opposite effect and made the RCCT easier because colour facilitated clearer discrimination between target and distracters. Ten-year-olds performed significantly better than 7- to 8-year-olds. The RCCT significantly correlated with children's performance on the Raven's Coloured Progressive Matrices Test (RCPM) presumably due to the shared multiple-choice format, but the RCCT was easier, as it did not require sequencing. Children from families with a high socio-economic status performed best on both tests, with boys outperforming girls on the more difficult RCCT test sections. PMID- 27375977 TI - In vitro and in vivo probiotic assessment of Leuconostoc mesenteroides P45 isolated from pulque, a Mexican traditional alcoholic beverage. AB - Pulque is a Mexican traditional alcoholic, non-distilled, fermented beverage produced by the fermentation of the sap, known as aguamiel, extracted from several maguey (Agave) species. Pulque has traditionally been considered a healthy beverage due to its nutrient content and also a traditional medicine for the treatment of gastrointestinal disorders and intestinal infections. During pulque fermentation, the development of acidity, alcohol and viscosity define its final sensorial properties, developing an enriched environment where dominant lactic acid bacteria (LAB), including diverse Leuconostoc species, are present. Because traditional pulque is consumed directly from the fermentation vessel, the naturally associated LAB are ingested and reach the human small intestine alive. Here, we report the in vitro and in vivo probiotic assessment of Leuconostoc mesenteroides strain P45 isolated from pulque. This isolated LAB species exhibited lysozyme, acid (pH 3.5) and bile salts (0.1 and 0.3 % oxgall) resistance. Antibacterial activity against the pathogens Listeria monocytogenes, enteropathogenic Escherichia coli, Salmonella enterica serovar Typhi and S. enterica serovar Typhimurium were observed in assays involving cell-to-cell contact, cell-free 2* concentrated supernatants and cell-to-cell contact under exopolysaccharide-producing conditions. The in vivo probiotic assessment showed an anti-infective activity of L. mesenteroides P45 against S. enterica serovar Typhimurium in challenged male and female BALB/c mice. Analysis of the available genome sequence of strain P45 allowed identified a pre-bacteriocin coding gene and six peptidoglycan hydrolase enzymes, probably involved in the antimicrobial activity of this strain. The results presented in this study support some potential microbial mechanisms associated with the beneficial effects on human health of this LAB involved in the fermentation of pulque. PMID- 27375978 TI - Pooled bioequivalence study database from Turkey: characterization of adverse events and determination of split points based on Gini Index as a promising method. AB - BACKGROUND: Manufacturing of and medication with generic drugs is increasing around the world. Bioequivalence (BE) studies are being performed routinely by Contract Research Organisations (CROs) in Turkey. However, an overall evaluation for the attended volunteers, examined Active Pharmaceutical Ingredients (APIs) and the observed adverse events have not been studied in the field. OBJECTIVE: Our aim was to revisit and compile the BE studies carried out between the years 2000-2013 of a CRO (N-CRO) in Turkey. METHODS: A dataset of 261 BE studies has been created for the observed adverse events with regards to the frequency, type, and drug subgroups. As an advanced evaluation, the Gini Index method has been used in the 63 available BE studies to obtain split points for two pharmacokinetic parameters, area under the plasma/serum concentration (AUC) and maximum plasma/serum concentration (Cmax), in order to investigate their likely effect on the adverse events. RESULTS: Thousand six hundred and forty two adverse events were found in the 261 BE studies involving 7828 volunteers with the frequency of 6.29 per study and 0.21 per volunteer. The most frequently observed adverse events were; headache, somnolence, nausea, dizziness and vomiting, respectively. Hundred and nine different APIs were observed. 'Genitourinary system and sex hormones' subgroup drugs had the highest frequency of the adverse events. Adverse event frequencies above the identified split points for Cmax and AUC values were higher than the frequencies below them. CONCLUSION: The review of 13 years period of BE studies revealed that the demographic properties of the volunteers and the study designs were in compliance with national and international guidelines. The promising outcome could be showing the increase of the adverse event frequencies above the obtained split points as the reflection of the likely individual pharmacokinetic differences in the adverse event occurence. PMID- 27375979 TI - Changing the thickness of two layers: i-ZnO nanorods, p-Cu2O and its influence on the carriers transport mechanism of the p-Cu2O/i-ZnO nanorods/n-IGZO heterojunction. AB - In this study, two layers: i-ZnO nanorods and p-Cu2O were fabricated by electrochemical deposition. The fabricating process was the initial formation of ZnO nanorods layer on the n-IGZO thin film which was prepared by sputtering method, then a p-Cu2O layer was deposited on top of rods to form the p-Cu2O/i-ZnO nanorods/n-ZnO heterojunction. The XRD, SEM, UV-VIS, I-V characteristics methods were used to define structure, optical and electrical properties of these heterojunction layers. The fabricating conditions and thickness of the Cu2O layers significantly affected to the formation, microstructure, electrical and optical properties of the junction. The length of i-ZnO nanorods layer in the structure of the heterojunction has strongly affected to the carriers transport mechanism and performance of this heterojunction. PMID- 27375980 TI - SNP haplotyping technique for evaluation of MGP 5' UTR power in osteoblast cells. AB - Matrix Gla protein (MGP) is involved in calcium trafficking and arterial calcification. The aim of study was to investigate the role of three polymorphisms within the MGP gene promoter region on reporter gene (luciferase) expression level. The fragments containing rs1800799 (C/T), rs1800802 (T/C), and rs1800801 (G/A) sites were constructed and transferred into human G292 osteoblast cells using pGL3-Basic plasmid. The reporter gene expression was calculated for the high and low frequency polymorphic haplotypes (CTG and TCA, respectively). Results showed that the reporter gene expression levels are not statistically different (p > 0.3). We concluded that the investigated polymorphic sites are not able to change the gene expression pattern in human G292 osteoblast cells. PMID- 27375981 TI - Impact of psychological inflexibility on depressive symptoms and sleep difficulty in a Japanese sample. AB - BACKGROUND: Psychological inflexibility is a core concept in the acceptance and commitment therapy (ACT) model. The current study hypothesized and tested two models in which psychological inflexibility was linked with higher levels of depressive symptoms and sleep difficulty. RESULTS: To attain data, Japanese university students (N = 633) completed questionnaires related to psychological inflexibility, depressive symptoms, and sleep difficulty. Psychological inflexibility was significantly correlated with higher levels of both depressive symptoms (r = 0.61) and sleep difficulty (r = 0.39). Structural equation modeling showed that psychological inflexibility was associated with higher levels of depressive symptoms after controlling for the effect of sleep difficulty. Additionally, psychological inflexibility was correlated with higher levels of sleep difficulty after controlling for the effect of depressive symptoms. These findings might assist with motivating clinicians to use ACT for insomnia. CONCLUSIONS: The current study found that greater psychological inflexibility was linked with high levels of depressive symptoms and sleep difficulties. These findings might assist with motivating clinicians to use ACT for insomnia. PMID- 27375982 TI - Missing phonemes are perceptually restored but differently by native and non native listeners. AB - This study investigates how similarly present and absent English phonemes behind noise are perceived by native and non-native speakers. Participants were English native speakers and Japanese native speakers who spoke English as a second language. They listened to English words and non-words in which a phoneme was covered by noise (added; phoneme + noise) or replaced by noise (replaced; noise only). The target phoneme was either a nasal (/m/ and /n/) or a liquid (/l/ and /r/). In experiment, participants listened to a pair of a word (or non-word) with noise (added or replaced) and a word (or non-word) without noise (original) in a row, and evaluated the similarity of the two on an eight-point scale (8: very similar, 1: not similar). The results suggested that both native and non-native speakers perceived the 'added' phoneme more similar to the original sound than the 'replaced' phoneme to the original sound. In addition, both native and non native speakers restored missing nasals more than missing liquids. In general, a replaced phoneme was better restored in words than non-words by native speakers, but equally restored by non-native speakers. It seems that bottom-up acoustic cues and top-down lexical cues are adopted differently in the phonemic restoration of native and non-native speakers. PMID- 27375983 TI - Diversity climate enhances work outcomes through trust and openness in workgroup communication. AB - Diversity climate, defined as an organizational climate characterized by openness towards and appreciation of individual differences, has been shown to enhance outcomes in culturally diverse teams. To date, it remains unclear which processes are responsible for these findings. This paper presents two quantitative studies (n = 91; 246) that identify trust and openness in workgroup communication as possible mediators. We replicate earlier findings that perceived diversity climate positively relates to job satisfaction, sense of inclusion, work group identification and knowledge sharing in teams. In study 1, trust is shown to mediate the effects of perceived diversity climate on team members' sense of inclusion. In study 2, trust mediates the relationship between perceived diversity climate and workgroup identification and openness mediates its relationship with knowledge sharing. PMID- 27375984 TI - Accumulation of heavy metals in mosses: a biomonitoring study. AB - The metropolitan area of the Toluca Valley (MATV) extends over an area of 1208.55 km(2) and has 1,361,500 inhabitants making it the fifth highest populated area in the country and the second highest in the state. The MATV has several environmental problems, with regards to the air quality. Particles PM10 and PM2.5 are considered to be the main pollutant due to these particles frequently exceeding the limit laid down in the standards of the air quality in the country. For this reason, samples of the mosses Fabriona ciliaris and Leskea angustata were collected at different sites in MATV, Mexico in order to establish the atmospheric deposition of heavy metals by means of the analysis of the mosses tissues. Results show the average metal concentrations in the mosses in the order of: Zn > Pb > Cr > Cd. The concentration capacities of heavy metals were higher in Fabriona ciliaris than Leskea angustata. Enrichment factors for Cr, Zn, Pb and Cd were obtained using the soils from the same sampling area. Enrichment factors results show that Cr is conservative in both sampling seasons with a terrigenous origin; Zn is moderately enriched in both sampling seasons and mainly associated to pedological-soil or substrate contribution and anthropogenic activities and Cd is highly enriched in the rainy season and Pb is highly enriched in both sampling seasons, with a predominantly anthropogenic origin. This study provides information to be considered in the strategies for similar environmental problems in the world. PMID- 27375985 TI - Pressure-controlled inverse ratio ventilation as a rescue therapy for severe acute respiratory distress syndrome. AB - PURPOSE: Low tidal volume ventilation improves the outcomes of acute respiratory distress syndrome (ARDS). However, no studies have investigated the use of a rescue therapy involving mechanical ventilation when low tidal volume ventilation cannot maintain homeostasis. Inverse ratio ventilation (IRV) is one candidate for such rescue therapy, but the roles and effects of IRV as a rescue therapy remain unknown. METHODS: We undertook a retrospective review of the medical records of patients with ARDS who received IRV in our hospital from January 2007 to May 2014. Gas exchange, ventilation, and outcome data were collected and analyzed. RESULTS: Pressure-controlled IRV was used for 13 patients during the study period. Volume-controlled IRV was not used. IRV was initiated on 4.4 ventilation days when gas exchange could not be maintained. IRV significantly improved the PaO2/FiO2 from 76 +/- 27 to 208 +/- 91 mmHg without circulatory impairment. The mean duration of IRV was 10.5 days, and all survivors were weaned from mechanical ventilation and discharged. The 90-day mortality rate was 38.5 %. Univariate analysis showed that the duration of IRV was associated with the 90-day mortality rate. No patients were diagnosed with pneumothorax. CONCLUSIONS: Pressure controlled IRV provided acceptable gas exchange without apparent complications and served as a successful bridge to conventional treatment when used as a rescue therapy for moderate to severe ARDS. PMID- 27375986 TI - Assessment of feed resources, feeding practices and coping strategies to feed scarcity by smallholder urban dairy producers in Jimma town, Ethiopia. AB - Smallholder dairy production is increasingly becoming popular in Jimma town. However, feed shortage is a major constraint to dairy production. The objectives of this study was to assess feed resources, feeding practices and farmers' perceived causes of feed shortage and coping strategies to feed scarcity in smallholder dairy producers in Jimma town, Oromia Regional State, Ethiopia. A total of 54 randomly selected dairy farmers were interviewed using a pre-tested structured questionnaire and through direct observations. Twenty major feed types used by dairy farmers were identified and categorized into five classes: natural pasture grazing, green feeds, hay, concentrate (commercial mix and agro industrial by-products) and non-conventional feed resources. Green feeds-fresh or succulent grasses and legumes (mean rank = 0.361), concentrate (0.256), hay (0.198), non-conventional feeds (0.115) and natural pasture grazing (0.070) were ranked as the main feed resources in that order of importance. Green feed (94.4 % of the respondents) was found to be the main basal diet of dairy cattle. Overall, wheat bran (85.2 % of the respondents), commercial concentrate (55.6 %), noug (Guizotia abyssinica) cake (20.4 %), cotton seed cake (7.4 %) and molasses (7.4 %) were the main concentrate supplements used (P > 0.05). Local brew waste (attela) (77.8 % of the respondents), bean and pea hulls (42.6 %) enset (Ensete ventricosum) leaf and pseudo-stem (37 %), sugarcane tops (33.3 %), banana leaf and stem/stover (16.7 %) and papaya stem (16.7 %) were the dominant non conventional feed resources in the surveyed area (P > 0.05). About 79.6, 7.4, 1.9 and 11.1 % of the farmers used zero-, semi-zero-, and the combination of zero- and semi-zero- and free-grazing systems, respectively. Most farmers (90.7 %) offered concentrate supplements to milking cows. However, supplementation did not consider milk yield, physiological status and condition of cows. All the farmers (100 %) offered common salt to their cattle as mineral supplement. The majority (98.1 %) of the farmers experience feed shortage in the dry season. Land scarcity (55.6 % of the respondents) was reported as the most important cause of feed scarcity followed by a combination of land scarcity and poor feed availability (42.2 %). Increasing use of agro-industrial by-products and commercial concentrate mix (87 % of the respondents), increasing use of hay (74.1 %), increasing use of non-conventional feeds (50 %), purchasing green feeds (19.8 %) and reducing herd size (2.7 %) were the strategies adopted for coping with feed scarcity. From results of this study, it could be concluded that to ensure sustainable availability of dairy cattle feed in the surveyed area, technological, technical and institutional innovations would be vital. PMID- 27375987 TI - Effect of dried Chlorella vulgaris and Chlorella growth factor on growth performance, meat qualities and humoral immune responses in broiler chickens. AB - This experiment was carried out to investigate the effects of dried chlorella powder (Chlorella vulgaris; DCP) and chlorella growth factor (CGF) on growth performance, serum characteristics, meat qualities and humoral immune responses in broiler chicks. A total of 1050 day-old Ross male broiler chicks were randomly divided into 35 pens (30 chicks/pen) and subjected to one of seven dietary treatments. A non-medicated corn-soybean meal base diet was considered as negative control (NC) and added with either antibiotic (PC), three levels of DCP (NC diets added with 0.05, 0.15 or 0.5 % DCP) or two levels of CGF (NC diets added with 0.05 or 0.15 % CGF). The final body weight and daily weight gain in PC and groups fed diets with 0.15 or 0.5 % DCP were heavier (p < 0.001) than those of NC and CGF-treated groups. Serum total lipid concentrations were lower (p = 0.001) in groups fed diets with 0.5 % DCP and 0.05 or 0.15 % CGF compared with PC group. The levels of serum IgG (p = 0.050) and IgM (p = 0.010) were elevated in chicks fed diets with DCP and CGF compared with the PC or NC group. Meat qualities such as cooking loss, meat color, and pH, of edible meats were not altered by dietary treatments. Collectively, these results indicate that dietary DCP, but not CGF, exerted growth-promoting effect, and both DCP and CGF affected humoral immune response in broiler chicks. PMID- 27375988 TI - Simultaneous decompression of the orbital lateral wall and optic canal for fibrous dysplasia in early adolescence. AB - INTRODUCTION: Patients with fronto-orbital fibrous dysplasia (FD) occasionally present fronto-orbital protrusion, exophthalmos, and visual acuity disturbance. Simultaneous management of these conditions has not been previously described. CASE DESCRIPTION: A-10-year-old female with fronto-orbital FD complained of left visual acuity disturbance. Head computed tomography showed compressed optic canal secondary to thickened bone. Decompression of the optic canal via the left frontotemporal extradural approach, opening of the lateral orbital wall, and dissection of the prominent zygoma were done simultaneously. The patient's visual acuity disturbance and exophthalmos subsequently improved postoperatively. DISCUSSION AND EVALUATION: When optic canal decompression is performed by the fronto-temporal approach, opening of the lateral orbital wall can be done simultaneously to decrease the intraorbital pressure and to prevent exophthalmos. In addition, although aesthetic plastic surgery is not generally recommended during the growing phase (due to the possibility of recurrence), this approach can prevent skin loosening and adverse cosmetic outcomes. CONCLUSIONS: Aesthetic plastic surgery for fronto-orbital FD is recommended to prevent skin loosening. Opening of the lateral orbital wall should be performed when optic canal decompression is planned. PMID- 27375989 TI - Personal values, subjective well-being and destination-loyalty intention of international students. AB - What are the factors that predict international students' destination-loyalty intention? This is the main question this paper addresses, using an online survey among 396 (short-term, N = 182) and (long-term, N = 214) international students at a Norwegian university. Structural equation model-AMOS was conducted to examine relationships among personal values, subjective well-being and destination-loyalty intentions. The results showed that: (1) universalism was positively related to subjective well-being for short-term students; and (2) subjective well-being was positively related to destination-loyalty intention for all groups. We found that relatively stable and happy individuals might be important for ensuring destination-loyalty intentions. Results also indicated that personal values that emphasize justice and equity are also important for short-term international students' well-being. PMID- 27375990 TI - Results from a pharmacy-based patient survey on the use of a fixed combination analgesic containing acetylsalicylic acid, paracetamol and caffeine by self diagnosing and self-treating patients. AB - BACKGROUND: Patients suffering from migraine or tension-type headache (TTH) often treat their complaints with over-the-counter (OTC) medications. Fixed dose combinations of acetylsalicylic acid, paracetamol and caffeine (APC) are among the most commonly used analgesics, and their efficacy for treating acute headache pain has been well demonstrated. This investigation was run to better characterize patients who treat their headache with OTC APC combinations, as well as treatment effects. METHODS: A pharmacy-based patient survey in 164 German pharmacies was performed. Patients (age >=18 years) who purchased APC analgesics (of the brand Thomapyrin((r))) were handed a questionnaire, which had to be filled out at patients own discretion after taking the medication. Demographics, pain characteristics and perceived efficacy and tolerability data were analysed with descriptive statistics. RESULTS: Questionnaires from 1298 patients were analysed, of whom 71.9 % were females and 28.1 % were males. Headache patients were assigned to TTH or migraine according to diagnosis criteria of the International Headache Classification-II (ICHD-II), with 828 patients for TTH and 206 for migraine. About one third of patients in the subgroup migraine did not report their pain as migraine. Nausea, photophobia/phonophobia turned out to be the most distinguishing feature between migraine and TTH. The main reasons for purchasing the product were recommendation by the pharmacists (40.5 %) and/or friends or relatives (24.4 %). 74 % of TTH and 55 % of migraine patients reported onset of pain relief within the first 30 min. More than 90 % rated efficacy as well as tolerability to be "good" or "very good". CONCLUSIONS: The main reason for purchasing APC products in the pharmacy are TTH or migraine. About a third of patients fulfilling the IHCD-II criteria for migraine failed to recognize their headache as migraine. This could be explained e.g. by patients' misconceptions about their pain. Patients' assessments of efficacy and tolerability showed that the investigated APC combinations are valuable for the treatment of TTH and migraine headache. These data complement those of randomized clinical studies on such preparations. PMID- 27375991 TI - The analysis of the SIRS alcoholism models with relapse on weighted networks. AB - Two SIRS alcoholism models with relapse on networks with fixed and adaptive weight are introduced. The spread of alcoholism threshold [Formula: see text] is calculated by the next generation matrix method. For the model with fixed weight, we prove that when [Formula: see text] the alcohol free equilibrium is globally asymptotically stable, then the drinking crowd gradually disappear. When [Formula: see text], the alcoholism equilibrium is global attractivity, then the density of alcoholics will remain in a stable value. For the model with adaptive weight, we only make some numerical simulations. We also give two effective strategies. Our results show that the treatment of recuperator for stopping relapsing and preventing the susceptible people to drink are two effective measures to eliminate alcoholism problem, and preventing the susceptible people to drink is more effective when the proportion of recuperator to accept treatment is equal to the proportion of susceptible people to refuse drinking alcohol. PMID- 27375992 TI - A note on a difference-type estimator for population mean under two-phase sampling design. AB - In this manuscript, we have proposed a difference-type estimator for population mean under two-phase sampling scheme using two auxiliary variables. The properties and the mean square error of the proposed estimator are derived up to first order of approximation; we have also found some efficiency comparison conditions for the proposed estimator in comparison with the other existing estimators under which the proposed estimator performed better than the other relevant existing estimators. We show that the proposed estimator is more efficient than other available estimators under the two phase sampling scheme for this one example; however, further study is needed to establish the superiority of the proposed estimator for other populations. PMID- 27375993 TI - Improving fundamental movement skills in Hong Kong students through an assessment for learning intervention that emphasizes fun, mastery, and support: the A + FMS randomized controlled trial study protocol. AB - BACKGROUND: Assessment for learning has been identified as an effective strategy to help children learn more effectively. Developing children to master basic movement skills in primary school requires formative assessments to inform instruction and learning. This study reports the rationale and methods for an assessment-based intervention that emphasizes fun, mastery and support (A + FMS) designed to improve fundamental movement skill (FMS) proficiency of primary schoolchildren. METHODS/DESIGN: Utilizing a cluster randomized controlled trial, the A + FMS intervention was designed to improve FMS proficiency of Hong Kong Chinese schoolchildren. A target sample of 282 students or more from 10 Grade 3 classes (from five schools) will be recruited and randomly assigned into an experimental group or a wait-list control group. Competence motivation theory provided a framework for the intervention that emphasizes fun activities to develop basic fundamentals, improving mastery of movement, and providing support for teaching and learning skills. Primary outcome measures are the raw scores of six objectively measured FMS (i.e., jump, hop, skip, dribble, catch, and overhand throw). Secondary outcomes include self-reported measures: enjoyment in physical education, perceived physical competence, perceived skill competence, and perceived social support. Teachers in the experimental group are required to attend a six-h training workshop and integrate 550 min of assessment for learning strategies into their physical education lessons. Resources such as videos, skills checklists, and equipment will also be provided to support children to accumulate extra learning and practice time after school. The rate of changes in primary and secondary outcomes across the experimental and control groups will be compared to determine the effectiveness of the program. DISCUSSION: The A + FMS is an innovative school-based intervention targeting improvements in movement mastery by supporting physical education teachers in FMS instruction and assessment practices. The findings from the study may be used to guide pre service teacher education and continuous professional development in FMS teaching and assessment. Trial registration CUHK_CCRB00479. PMID- 27375994 TI - Factors affecting satisfaction on antenatal care services in Sarawak, Malaysia: evidence from a cross sectional study. AB - BACKGROUND: High levels of satisfaction among women with the antenatal care services will increase the compliance of antenatal visits during pregnancy. Thus, this study was done to assess the level of satisfaction among women on the quality of antenatal care received and the factors influencing thereof. METHODS: This was a cross-sectional study conducted in the three zones of Sarawak. Women aged 18 years and above, irrespective of ethnic groups, having children aged 3 years and below were included in the study. Data was collected by face-to-face interview using interview schedule. A validated Patient Satisfaction Questionnaire (PSQ-18) was used to assess the satisfaction with antenatal care. A total of 1236 data was analysed using IBM SPSS version 22.0. A p value <0.05 was considered as statistically significant. RESULTS: A multinomial logistic regression analysis revealed that Bidayuh 17.4 % was less likely to be highly satisfied with antenatal care. Similarly, respondents with secondary level of education 29.9 % were less likely to be highly satisfied, whereas, respondents having primary level of education, 1.6 % were less likely to be highly satisfied. However, those who did not spend any money as out of pocket expenses were 1.935 times more likely to be highly satisfied with antenatal care. CONCLUSION: Overall the studied women were satisfied with the antenatal care services. Ethnicity, level of education and out of pocket expenses appeared to be important predictors of satisfaction with antenatal care. The finding recommends the community-based and language-specific interventions should be implemented to sustain the satisfaction of maternal care. PMID- 27375995 TI - An assessment of the levels of perceived social support among older adults living with HIV and AIDS in Dublin. AB - OBJECTIVES: To determine the level of perceived social support among older adults living with HIV and AIDS in Dublin. METHODS: The study utilized a cross-sectional survey design to collect data from 46 adults aged 50 years or older who are members of open heart house (OHH) in Ireland, a peer support network for people living with HIV and AIDS. Participants completed a set of interviewer-assisted questionnaires, which included the multidimensional measure of perceived social support (PSS) to assess the level of social support. RESULTS: Levels of PSS among participants were observed as follows: 54 % had low PSS, 33 % had a moderate PSS and 13 % had high PSS. A fifth of the study participants had a history of injection drug use (IDU) and this group reported higher PSS scores in general than non-IDU's (H = 79.500, Z = -2.678, p = 0.006). PSS scores were observed to be higher in general among participants with longer duration of infection [H(2) = 7.856, p = 0.020]. CONCLUSION: Despite its limitations, this study provides vital information about the level of social support among older people living with HIV and AIDS at OHH Dublin. An unexpected but interesting finding was the positive relationship between IDU and PSS level. Formulation of strategies to enable older PLHA to be more proactive members of their community through a peer support network sponsored volunteer services should be encouraged. PMID- 27375996 TI - A nonlinear bi-level programming approach for product portfolio management. AB - Product portfolio management (PPM) is a critical decision-making for companies across various industries in today's competitive environment. Traditional studies on PPM problem have been motivated toward engineering feasibilities and marketing which relatively pay less attention to other competitors' actions and the competitive relations, especially in mathematical optimization domain. The key challenge lies in that how to construct a mathematical optimization model to describe this Stackelberg game-based leader-follower PPM problem and the competitive relations between them. The primary work of this paper is the representation of a decision framework and the optimization model to leverage the PPM problem of leader and follower. A nonlinear, integer bi-level programming model is developed based on the decision framework. Furthermore, a bi-level nested genetic algorithm is put forward to solve this nonlinear bi-level programming model for leader-follower PPM problem. A case study of notebook computer product portfolio optimization is reported. Results and analyses reveal that the leader-follower bi-level optimization model is robust and can empower product portfolio optimization. PMID- 27375997 TI - The role of adjuvant chemotherapy for patients with stage II and stage III gastric adenocarcinoma after surgery plus D2 lymph node dissection: a real-world observation. AB - BACKGROUND: The influence of adjuvant chemotherapy on the survival of gastric adenocarcinoma patients in a stage-specific manner is controversial. METHODS: To further explore this topic, we retrospectively analyzed the impact of adjuvant chemotherapy on the clinical outcomes of 77 stage II and 117 stage III patients diagnosed between January 2008 and December 2012. RESULTS: All 194 patients underwent radical operation plus D2 dissection, and were followed a median time of 23.3 (range 0.4-80.2) months. Median patient age was 67.7 (range 33.9-97.5) years. Adjuvant chemotherapy prolonged the relapse-free survival [22.9 (95 % confidence interval 9.4-36.4) vs. 14.2 (95 % CI 8.6-19.8) months, P = 0.009] and overall survival [32.3 (95 % CI 22.6-42.0) vs. 13.4 (95 % CI 9.5-17.2) months, P < 0.001] for patients with stage III, but not stage II, disease. Higher overall survival from adjuvant chemotherapy in stage II patients with node involvement did not reach the level of statistical significance (P = 0.102). To reduce the selection bias, 142 patients aged <75 years were included in a subgroup analysis in which the benefit of adjuvant chemotherapy on relapse-free survival and overall survival were demonstrated for patients with stage III disease. CONCLUSIONS: Adjuvant chemotherapy prolongs relapse-free and overall survival for patients with stage III gastric cancer in a real-world situation. Tailoring therapy based on different characteristics for patients with stage II gastric cancer may produce better outcomes. PMID- 27375998 TI - Applying machine learning techniques to the identification of late-onset hypogonadism in elderly men. AB - In the diagnosis of late-onset hypogonadism (LOH), the Androgen Deficiency in the Aging Male (ADAM) questionnaire or Aging Males' Symptoms (AMS) scale can be used to assess related symptoms. Subsequently, blood tests are used to measure serum testosterone levels. However, results obtained using ADAM and AMS have revealed no significant correlations between ADAM and AMS scores and LOH, and the rate of misclassification is high. Recently, many studies have reported significant associations between clinical conditions such as the metabolic syndrome, obesity, lower urinary tract symptoms, and LOH. In this study, we sampled 772 clinical cases of men who completed both a health checkup and two questionnaires (ADAM and AMS). The data were obtained from the largest medical center in Taiwan. Two well known classification techniques, the decision tree (DT) and logistic regression, were used to construct LOH prediction models on the basis of the aforementioned features. The results indicate that although the sensitivity of ADAM is the highest (0.878), it has the lowest specificity (0.099), which implies that ADAM overestimates LOH occurrence. In addition, DT combined with the AdaBoost technique (AdaBoost DT) has the second highest sensitivity (0.861) and specificity (0.842), resulting in having the best accuracy (0.851) among all classifiers. AdaBoost DT can provide robust predictions that will aid clinical decisions and can help medical staff in accurately assessing the possibilities of LOH occurrence. PMID- 27375999 TI - Application research of computational mass-transfer differential equation in MBR concentration field simulation. AB - After conducting the intensive research on the distribution of fluid's velocity and biochemical reactions in the membrane bioreactor (MBR), this paper introduces the use of the mass-transfer differential equation to simulate the distribution of the chemical oxygen demand (COD) concentration in MBR membrane pool. The solutions are as follows: first, use computational fluid dynamics to establish a flow control equation model of the fluid in MBR membrane pool; second, calculate this model by adopting direct numerical simulation to get the velocity field of the fluid in membrane pool; third, combine the data of velocity field to establish mass-transfer differential equation model for the concentration field in MBR membrane pool, and use Seidel iteration method to solve the equation model; last but not least, substitute the real factory data into the velocity and concentration field model to calculate simulation results, and use visualization software Tecplot to display the results. Finally by analyzing the nephogram of COD concentration distribution, it can be found that the simulation result conforms the distribution rule of the COD's concentration in real membrane pool, and the mass-transfer phenomenon can be affected by the velocity field of the fluid in membrane pool. The simulation results of this paper have certain reference value for the design optimization of the real MBR system. PMID- 27376000 TI - Developing a weighted reward criterion for the Markov-based decision of road maintenance. AB - Reward criterion is an important decision factor in a Markov-based road maintenance optimization model. At present, average reward criterion or discounted reward criterion is widely used to optimize life cycle costs of road maintenance. However, the former one cannot reflect the time value of life cycle costs whereas the latter one tends to neglect the costs accumulated in the later periods over the decision horizon. In this regard, a weighted reward criterion is developed for the Markov-based road maintenance optimization model. It measures the trade-off of the average reward and the discounted reward by setting the weights of two rewards. In addition, the existence of the optimal plan under the weighted reward criterion is proven by two numerical examples under two scenarios with and without considering the inflation on maintenance costs. Finally, comparison is conducted between the proposed criterion and the average reward criterion/the discounted reward criterion to check the impacts of discount rates and inflation rates on the optimal plan. PMID- 27376001 TI - Biosynthesis of Se-methyl-seleno-l-cysteine in Basidiomycetes fungus Lentinula edodes (Berk.) Pegler. AB - BACKGROUND: The aim of the current study was to investigate whether the Basidiomycetes fungus Lentinula edodes can biosynthesize Se-methyl-seleno-l cysteine, a seleno-amino acid with strong anticancer activity, and to optimize the culture conditions for its biosynthesis. We hypothesize that preparations obtained from Se-methyl-seleno-l-cysteine-enriched mycelia from this medicinal mushroom would possess stronger cancer-preventive properties than current preparations. RESULTS: By optimizing the concentration of selenium in the culture medium, we increased the mycelial concentration of Se-methyl-seleno-l-cysteine from essentially non-detectable levels to 120 ug/g dry weight. Significantly elevated levels of this amino acid also correlated with significant (twofold) inhibition of mycelial growth. Increases in the concentration of mycelial Se methyl-seleno-l-cysteine appeared to be highly correlated with the enhanced biosynthesis of selenomethionine and total selenium content in mycelium. CONCLUSIONS: We have demonstrated that in L. edodes, enhanced biosynthesis of this non-protein amino acid eliminates excess selenium. PMID- 27376002 TI - Range expansion of the invasive insect Greenidea (Trichosiphon) psidii (Hemiptera: Aphididae) in the Neotropical Region. AB - Greenidea psidii is an invasive insect from Asia that feeds on a diverse variety of agriculturally and environmentally important plant species. As an essential component of research necessary for development of a better understanding of biodiversity and its conservation, this study documents a major recent expansion in range of G. psidii in the Neotropics to the region of the tropical restinga ecosystem of Brazil, where it was found infesting guava (Psidium guajava) and jabuticaba (Plinia cauliflora). A summary of information on the geographic distribution, host plants, identification, and potential natural enemies of G. psidii that may be useful for integrated management of this pest in the Neotropical Region and other areas where this invasive insect has recently become established and is likely to further spread is also provided. PMID- 27376003 TI - Diagnostic accuracy of metastatic axillary lymph nodes in breast MRI. AB - PURPOSE: The most important prognostic variable for early stage breast cancer is the status of axillary lymph nodes. The aim of this study was to evaluate the diagnostic accuracy of preoperative magnetic resonance imaging (MRI) for metastatic axillary lymph node in breast cancer cases with post-operative sentinel lymph node biopsy (SLNB) results. MATERIALS AND METHODS: Women aged between 21 and 73 years who were diagnosed with malignant mass lesion of the breast between 2013 and 2015 were included in this study. The preoperative MR images of patients with diagnosis of breast cancer was evaluated to determine axillary lymph node status. Axillary lymph node size, long axis to short axis ratio, lymph node contours, cortical thickness to anteroposterior diameter ratio, the presence of a fatty hilum and contrast enhancement patterns (homogenous or heterogenous) was noted. Additionally, the presence of comet tail sign which a tail extending from an enhancing breast lesion into the parenchyma and might represent ductal infiltration on post-contrast series was also noted. All data obtained from this evaluation was compared with postoperative SLNB results. RESULTS: Metastatic nodes were found to have a longer short axis when compared to reactive nodes (p = 0.042; p < 0.05). The long axis to short axis ratio was notably lower in metastatic nodes when compared to reactive nodes. Cortical thickness was higher in metastatic nodes when compared to reactive nodes (p = 0.024; p < 0.05). Comet sign was observed in 15 of metastatic nodes (73.3 %) and in one (5 %) reactive node. This difference was statistically significant (p = 0.001; p < 0.01). While fatty hilum was seen in 40 % of metastatic nodes (n = 6), it was seen in all (n = 20) reactive nodes. This difference was statistically significant (p = 0.001; p < 0.01). CONCLUSIONS: MRI is a non invasive sensitive and specific imaging modality for evaluating the axilla. We have shown that with the help of comet tail sign and status of fatty hilum contrast enhanced MRI has the highest sensitivity of 84.7 % for detecting axillary lymph node metastases (Singletary et al. in Semin Surg Oncol 21(1):53-59, 2003). PMID- 27376004 TI - Determination of optimal parameters of MAFFT program based on BAliBASE3.0 database. AB - BACKGROUND: Multiple sequence alignment (MSA) is one of the most important research contents in bioinformatics. A number of MSA programs have emerged. The accuracy of MSA programs highly depends on the parameters setting, mainly including gap open penalties (GOP), gap extension penalties (GEP) and substitution matrix (SM). This research tries to obtain the optimal GOP, GEP and SM rather than MAFFT default parameters. RESULTS: The paper discusses the MAFFT program benchmarked on BAliBASE3.0 database, and the optimal parameters of MAFFT program are obtained, which are better than the default parameters of CLUSTALW and MAFFT program. CONCLUSIONS: The optimal parameters can improve the results of multiple sequence alignment, which is feasible and efficient. PMID- 27376005 TI - Modeling the prediction of business intelligence system effectiveness. AB - Although business intelligence (BI) technologies are continually evolving, the capability to apply BI technologies has become an indispensable resource for enterprises running in today's complex, uncertain and dynamic business environment. This study performed pioneering work by constructing models and rules for the prediction of business intelligence system effectiveness (BISE) in relation to the implementation of BI solutions. For enterprises, effectively managing critical attributes that determine BISE to develop prediction models with a set of rules for self-evaluation of the effectiveness of BI solutions is necessary to improve BI implementation and ensure its success. The main study findings identified the critical prediction indicators of BISE that are important to forecasting BI performance and highlighted five classification and prediction rules of BISE derived from decision tree structures, as well as a refined regression prediction model with four critical prediction indicators constructed by logistic regression analysis that can enable enterprises to improve BISE while effectively managing BI solution implementation and catering to academics to whom theory is important. PMID- 27376006 TI - Remodeling an infarcted heart: novel hybrid treatment with transmyocardial revascularization and stem cell therapy. AB - Transmyocardial revascularization (TMR) has emerged as an additional therapeutic option for patients suffering from diffuse coronary artery disease (CAD), providing immediate angina relief. Recent studies indicate that the volume of surgical cases being performed with TMR have been steadily rising, utilizing TMR as an adjunctive therapy. Therefore the purpose of this review is to provide an up-to-date appreciation of the current state of TMR and its future developmental directions on CAD treatment. The current potential of this therapy focuses on the implementation of stem cells, in order to create a synergistic angiogenic effect while increasing myocardial repair and regeneration. Although TMR procedures provide increased vascularization within the myocardium, patients suffering from ischemic cardiomyopathy may not benefit from angiogenesis alone. Therefore, the goal of introducing stem cells is to restore the functional state of a failing heart by providing these cells with a favorable microenvironment that will enhance stem cell engraftment. PMID- 27376007 TI - Effect of proteolytic activities in combination with the pectolytic activities on extractability of the fat and phenolic compounds from olives. AB - During the extraction, a portion of oil remains trapped inside the cells and its release requires the degradation of the walls and cell membranes, especially when the fruits have not reached a maximum maturity which is likely to cause an optimal embrittlement of the parietal structures and cell membrane. This can be done by specific enzymes necessary for the degradation of various cellular barriers. Three different enzyme treatments proteolytic, pectolytic or both are applied on the Moroccan Picholine olives from veraison to maturity of the fruit. The effect of these treatments is evaluated by olive oil diffusion, its phenolic content (PC) and cellular embrittlement determination of olives during ripening. The pectolytic activities lead to a significant increase in both the oil extractability (76 % at veraison and 14 % at maturity) and the PC (up to 50 % of gain compared to the control at veraison and 27 % at maturity). The proteolytic activities applied alone have no significant effect on the extractability and the polyphenols levels of oils. Furthermore, when these proteolytic activities are added in combination with the pectolytic activities, the oil extractability is doubled at veraison and its flowing up to 99 % at maturity that barely 84 % in the control in addition to a richness of polyphenols which can reach 84 % more compared to the control. This increase in polyphenols wealth is probably due to the degradation of cell walls, cellular and vacuolar membranes by enzyme activities releasing PCs that were previously associated with these structures in the drupe. PMID- 27376008 TI - Exploration of virtual body-representation in adolescence: the role of age and sex in avatar customization. AB - The malleable nature of the self led researchers to investigate the meaning of virtual identity by exploring virtual self-representation through avatars and its association with users' identity. The present study aims to investigate the changes in virtual body-representation in adolescence related to age levels and sex and the association with adolescents' self-esteem and body esteem. Anthropometric features, body esteem and self-esteem were used to assess adolescents' body image and identity. The scoring code of the "Drawing Me" graphical test was used to evaluate the avatars. The sample is composed of 63 adolescents of different ages-early, middle and late adolescence-balanced by sex. Results show that the creation of a digital avatar changes with age and is partially associated with adolescents' perceptions in terms of body esteem and self-esteem. Moreover, the creation of avatars occurs differently for boys, who enrich their avatars with many sexual features, than for girls, who prefer to detail their avatars' clothing to enrich them. Critical reflections and implications for psychological interventions that may use avatars to investigate adolescents' identity in integration with other tools will be discussed. PMID- 27376009 TI - Effects of substrates on N2O emissions in an anaerobic ammonium oxidation (anammox) reactor. AB - N2O emission in the anaerobic ammonium oxidation (anammox) process is of growing concern. In this study, effects of substrate concentrations on N2O emissions were investigated in an anammox reactor. Extremely high N2O emissions of 1.67 % were led by high NH4-N concentrations. Results showed that N2O emissions have a positive correlation with NH4-N concentrations in the anammox reactor. Reducing NH4-N concentrations by recycling pump resulted in decreasing N2O emissions. In addition, further studies were performed to identify a key biological process that is contributed to N2O emissions from the anammox reactor. Based on the results obtained, Nitrosomonas, which can oxidize ammonia to nitrite, was deemed as the main sources of N2O emissions. PMID- 27376010 TI - Pterocellin A isolated from marine bryozoan Pterocella vesiculosa is cytotoxic to human HeLa cells via mitochondrial apoptotic processes. AB - Pterocellin A is a novel bioactive alkaloid isolated from the New Zealand marine bryozoan Pterocella vesiculosa. It exhibits potent antitumour activity towards the P388 (murine leukaemia) cell line in vitro and is selectively sensitive towards certain non-small cell lung, melanoma, and breast cancer cell lines, however, the biological mode of action of pterocellin A is unknown. Using the human cervical cancer cell line HeLa, we show that pterocellin A exhibited cytotoxicity against HeLa cells with an IC50 of 886 ng/mL. Time-course MTT and LDH assays were carried out and the results showed only a low level of cytosolic LDH was detected in the supernatant after all the cells have died from pterocellin A treatment at 2000 ng/mL. This indicated the cells maintained membrane integrity upon cell death which suggested apoptotic cell death. Additionally, morphological changes were observed under the microscope after 6 h of treatment. Cell shrinkage and nucleus condensation were observed, as well as apparent membrane blebbing, a key feature of apoptosis. The MTT data was also indicative of mitochondria impairment which could suggest that pterocellin A targets the mitochondria. This idea was supported by the observed changes in the morphology and location of the mitochondria after exposure to pterocellin A. Furthermore, the level of activated caspase-3 in HeLa cells increased after treatment with pterocellin A; activated caspase-3 can only be detected after a series of signalling events following the induction of apoptosis. These data support the notion that pterocellin A is an inducer of apoptosis in HeLa cells possibly via mitochondria related processes. PMID- 27376011 TI - CXCL13 chemokine as a promising biomarker to diagnose neurosyphilis in HIV negative patients. AB - BACKGROUND: Chemokine ligand 13 (CXCL13) is believed to play a role in the recruitment of B cells in the central nervous system during neuroinflammation. Neurosyphilis is a group of clinical syndromes of the central nervous system caused by Treponema pallidum (T. pallidum) infection. The relationship between CXCL13 and neurosyphilis still needs further study. In our study, CSF and serum CXCL13 concentrations were detected among 40 neurosyphilis patients, 31 syphilis/non-neurosyphilis patients, 26 non-syphilis/other central nervous system diseases patients. Serum CXCL13 concentrations were detected in 49 healthy persons. All enrolled persons were HIV-negative. Receiver operating characteristic (ROC) analysis was performed to determine the threshold value that could distinguish neurosyphilis from syphilis. RESULTS: We found that the CSF CXCL13 concentrations and CXCL13 quotient (QCXCL13) were significantly increased in neurosyphilis patients compared to syphilis/non-neurosyphilis (chi(2) = 21.802, P < 0.001) and non-syphilis patients (chi(2) = 7.677, P = 0.002). ROC curve analyses revealed that CSF CXCL13 concentrations and QCXCL13 could serve as valuable biomarkers for differentiating neurosyphilis from non neurosyphilis/syphilis. CONCLUSIONS: The CSF CXCL13 and QCXCL13 could serve as valuable biomarkers for differentiating neurosyphilis from non neurosyphilis/syphilis in HIV-negative patients. PMID- 27376013 TI - Influences of specific ions in groundwater on concrete degradation in subsurface engineered barrier system. AB - Many disposal concepts currently show that concrete is an effective confinement material used in engineered barrier systems (EBS) at a number of low-level radioactive waste (LLW) disposal sites. Cement-based materials have properties for the encapsulation, isolation, or retardation of a variety of hazardous contaminants. The reactive chemical transport model of HYDROGEOCHEM 5.0 was applied to simulate the effect of hydrogeochemical processes on concrete barrier degradation in an EBS which has been proposed to use in the LLW disposal site in Taiwan. The simulated results indicated that the main processes that are responsible for concrete degradation are the species induced from hydrogen ion, sulfate, and chloride. The EBS with the side ditch drainage system effectively discharges the infiltrated water and lowers the solute concentrations that may induce concrete degradation. The redox processes markedly influence the formations of the degradation materials. The reductive environment in the EBS reduces the formation of ettringite in concrete degradation processes. Moreover, the chemical conditions in the concrete barriers maintain an alkaline condition after 300 years in the proposed LLW repository. This study provides a detailed picture of the long-term evolution of the hydrogeochemical environment in the proposed LLW disposal site in Taiwan. PMID- 27376012 TI - Training for happiness: the impacts of different positive exercises on hedonism and eudaemonia. AB - Theoretical conceptions on happiness have generally considered two broad perspectives: hedonic enjoyment and eudaemonia. However, most research on how to improve people's happiness has focused primarily on the enhancement of hedonic happiness. In this longitudinal experimental study we test the differential impact of two positive exercises-Best Possible Selves and the Lottery Question-on hedonic and eudaemonic happiness. The hypothesis that the practice of the Best Possible Selves exercise would increase hedonic happiness was confirmed. This effect was immediate and maintained a week after the exercise. Furthermore, this exercise also increased eudaemonic happiness. However, its effect decreased after a week. Contrary to what was expected the Lottery Question exercise decreased both eudaemonic happiness and hedonic happiness over time. We discuss implications of this study for the literature on positive psychological and behavioral interventions to increase happiness. PMID- 27376014 TI - NaCl-, protease-tolerant and cold-active endoglucanase from Paenibacillus sp. YD236 isolated from the feces of Bos frontalis. AB - Bos frontalis, which consumes bamboo and weeds, may have evolved unique gastrointestinal microorganisms that digest cellulase. A Paenibacillus sp. YD236 strain was isolated from B. frontalis feces, from which a GH8 endoglucanase gene, pglue8 (1107 bp, 54.5 % GC content), encoding a 368-residue polypeptide (PgluE8, 40.4 kDa) was cloned. PgluE8 efficiently hydrolyzed barley-beta-d-glucan followed by CMC-Na, soluble starch, laminarin, and glucan from black yeast optimally at pH 5.5 and 50 degrees C, and retained 78.6, 41.6, and 34.5 % maximum activity when assayed at 20, 10, and 0 degrees C, respectively. Enzyme activity remained above 176.6 % after treatment with 10.0 mM beta-mercaptoethanol, and was 83.0, 78, and 56 % after pre-incubation in 30 % (w/v) NaCl, 16.67 mg/mL trypsin, and 160.0 mg/mL protease K, respectively. Cys23 and Cys364 residues were critical for PgluE8 activity. pglue8, identified from B. frontalis feces for the first time in this study, is a potential alternative for applications including food processing, washing, and animal feed preparation. PMID- 27376015 TI - Using Bayesian networks to guide the assessment of new evidence in an appeal case. AB - When new forensic evidence becomes available after a conviction there is no systematic framework to help lawyers to determine whether it raises sufficient questions about the verdict in order to launch an appeal. This paper presents such a framework driven by a recent case, in which a defendant was convicted primarily on the basis of audio evidence, but where subsequent analysis of the evidence revealed additional sounds that were not considered during the trial. The framework is intended to overcome the gap between what is generally known from scientific analyses and what is hypothesized in a legal setting. It is based on Bayesian networks (BNs) which have the potential to be a structured and understandable way to evaluate the evidence in a specific case context. However, BN methods suffered a setback with regards to the use in court due to the confusing way they have been used in some legal cases in the past. To address this concern, we show the extent to which the reasoning and decisions within the particular case can be made explicit and transparent. The BN approach enables us to clearly define the relevant propositions and evidence, and uses sensitivity analysis to assess the impact of the evidence under different assumptions. The results show that such a framework is suitable to identify information that is currently missing, yet clearly crucial for a valid and complete reasoning process. Furthermore, a method is provided whereby BNs can serve as a guide to not only reason with incomplete evidence in forensic cases, but also identify very specific research questions that should be addressed to extend the evidence base and solve similar issues in the future. PMID- 27376017 TI - Wellbeing in the Making: Peoples' Experiences with Wearable Activity Trackers. AB - BACKGROUND: Wearable activity trackers have become a viable business opportunity. Nevertheless, research has raised concerns over their potentially detrimental effects on wellbeing. For example, a recent study found that while counting steps with a pedometer increased steps taken throughout the day, at the same time it decreased the enjoyment people derived from walking. This poses a serious threat to the incorporation of healthy routines into everyday life. Most studies aim at proving the effectiveness of activity trackers. In contrast, a wellbeing-oriented perspective calls for a deeper understanding of how trackers create and mediate meaningful experiences in everyday life. METHODS: We present a study of real life experiences with three wearable activity trackers: Fitbit, Jawbone Up and Nike + Fuelband. Using need fulfillment as a theoretical lens, we study recent, memorable experiences submitted by 133 users of activity trackers. RESULTS: We reveal a two-dimensional structure of users' experience driven by the needs of physical thriving or relatedness. Our qualitative findings further show a nuanced picture of the adoption of activity trackers and their impact on wellbeing. For instance, while reflection about own exercising practices lost its relevance over time, users continued to wear the tracker to document and collect their runs. More than just supporting behavioral change, we find trackers to provide multiple psychological benefits. For instance, they enhance feelings of autonomy as people gain more control about their exercising regime. Others experience relatedness, when family members purchase a tracker for relatives and join them in their efforts towards a better, healthier self. CONCLUSIONS: The study highlights that activity trackers can be more than "tools" to change behavior. Through incorporation in daily life, they offer new social experiences, new ways of boosting our self-esteem and getting closer to our ideal selves. PMID- 27376016 TI - Treating Negative Symptoms in Schizophrenia: an Update. AB - Interest in the negative symptoms of schizophrenia has increased rapidly over the last several decades, paralleling a growing interest in functional, in addition to clinical, recovery, and evidence underscoring the importance negative symptoms play in the former. Efforts continue to better define and measure negative symptoms, distinguish their impact from that of other symptom domains, and establish effective treatments as well as trials to assess these. Multiple interventions have been the subject of investigation, to date, including numerous pharmacological strategies, brain stimulation, and non-somatic approaches. Level and quality of evidence vary considerably, but to this point, no specific treatment can be recommended. This is particularly problematic for individuals burdened with negative symptoms in the face of mild or absent positive symptoms. Presently, clinicians will sometimes turn to interventions that are seen as more "benign" and in line with routine clinical practice. Strategies include use of atypical antipsychotics, ensuring the lowest possible antipsychotic dose that maintains control of positive symptoms (this can involve a shift from antipsychotic polypharmacy to monotherapy), possibly an antidepressant trial (given diagnostic uncertainty and the frequent use of these drugs in schizophrenia), and non-somatic interventions (e.g., cognitive behavioral therapy, CBT). The array and diversity of strategies currently under investigation highlight the lack of evidence-based treatments and our limited understanding regarding negative symptoms underlying etiology and pathophysiology. Their onset, which can precede the first psychotic break, also means that treatments are delayed. From this perspective, identification of biomarkers and/or endophenotypes permitting earlier diagnosis and intervention may serve to improve treatment efficacy as well as outcomes. PMID- 27376018 TI - Methods, units and quality requirements for the analysis of haemoglobin A1c in diabetes mellitus. AB - The formation of glycohemoglobin, especially the hemoglobin A1c (HbA1c) fraction, occurs when glucose becomes coupled with the amino acid valine in the beta-chain of Hb; this reaction is dependent on the plasma concentration of glucose. Since the early 1970s it has been known that diabetics display higher values OF HbA1C because they have elevated blood glucose concentrations. Thus HbA1c has acquired a very important role in the treatment and diagnosis of diabetes mellitus. After the introduction of the first quantitative measurement OF HbA1C, numerous methods for glycohemoglobin have been introduced with different assay principles: From a simple mini-column technique to the very accurate automated high-pressure chromatography and lastly to many automated immunochemical or enzymatic assays. In early days, the results of the quality control reports for HbA1c varied extensively between laboratories, therefore in United States and Canada working groups (WG) of the Diabetes Controls and Complications Trial (DCCT) were set up to standardize the HbA1c assays against the DCCT/National Glycohemoglobin Standardization Program reference method based on liquid chromatography. In the 1990s, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) appointed a new WG to plan a reference preparation and method for the HBA1c measurement. When the reference procedures were established, in 2004 IFCC recommended that all manufacturers for equipment used in HbA1c assays should calibrate their methods to their proposals. This led to an improvement in the coefficient of variation (CV%) associated with the assay. In this review, we describe the glycation of Hb, methods, standardization of the HbA1c assays, analytical problems, problems with the units in which HbA1c values are expressed, reference values, quality control aspects, target requirements for HbA1c, and the relationship of the plasma glucose values to HbA1c concentrations. We also note that the acceptance of the mmol/mol system for HbA1c as recommended by IFCC, i.e., the new unit and reference ranges, are becoming only slowly accepted outside of Europe where it seems that expressing HbA1c values either only in per cent units or with parallel reporting of percent and mmol/mol will continue. We believe that these issues should be resolved in the future and that it would avoid confusion if mmol/mol unit for HbA1c were to gain worldwide acceptance. PMID- 27376019 TI - Methodology in improving antibiotic implementation policies. AB - The basic requirements of antibiotic prescribing are components of methodology; knowledge, logical reasoning, and analysis. Antimicrobial drugs are valuable but limited resources, different from other drugs and they are among the most commonly prescribed drugs all over the world. They are the only drugs which do not intentionally affect the patient. They affect the pathogens which invade the host. The emergence and spread of antibiotic-resistant pathogens are accelerated by heavy antibiotic usage. The effective antimicrobial stewardship and infection control program have been shown to limit the emergence of antimicrobial-resistant bacteria. In this respect, education for antibiotic prescribing could be designed by going through the steps of scientific methodology. A defined leadership and a coordinated multidisciplinary approach are necessary for optimizing the indication, selection, dosing, route of administration, and duration of antimicrobial therapy. In scenarios, knowledge is also as important as experience for critical decision making as is designated. In this setting, the prevalence and resistance mechanisms of antimicrobials, and their interactions with other drugs need to be observed. In this respect, infectious disease service should play an important role in improving antimicrobial use by giving advice on the appropriate use of antimicrobial agents, and implementing evidence-based guidelines. PMID- 27376020 TI - Rat model of cholelithiasis with human gallstones implanted in cholestasis induced virtual gallbladder. AB - AIM: To facilitate translational research on cholelithiasis, we have developed a rat model of human gallstones by exploiting the unique biliopancreatic features of this species. METHODS: Under anesthesia, 16 adult rats of equal genders underwent two times of abdominal surgery. First, their common bile duct (CBD) was ligated to cause cholestasis by total biliary obstruction (TBO). On day 0, 1, 3, 7, 14, 21 and 28 after TBO, magnetic resonance imaging (MRI) was conducted to monitor the dilatation of the CBD, and blood was sampled to analyze total serum bilirubin (TSB). Secondly, on day 30, the abdomen was re-opened and gallstone(s) collected from human patients were implanted in the dilated CBD as a virtual gallbladder (VGB), which was closed by suture ligation. This rat cholelithiasis model was examined by MRI, clinical observation, microcholangiography and histology. RESULTS: All rats survived two laparotomies. After ligation, the CBD was dilated to a stable size of 4 to 30 mm in diameter on day 21-28, which became a VGB. The rats initially showed signs of jaundice that diminished over time, which paralleled with the evolving TSB levels from 0.6 +/- 0.3 mg/dL before ligation, through a peak of 10.9 +/- 1.9 mg/dL on day 14, until a nearly normalized value after day 28. The dilated CBD with thickened wall allowed an incision for implantation of human gallstones of 1-10 mm in diameter. The rat cholelithiasis was proven by in vivo MRI and postmortem microcholangiography and histomorphology. CONCLUSION: A rat model cholelithiasis with human gallstones has been established, which proves feasible, safe, reliable, nontoxic and cost effective. Given the gallstones of human origin, applications of this model may be of help in translational research such as optical detection and lysis of gallstones by systemic drug administration. PMID- 27376021 TI - Mild oxidative stress is beneficial for sperm telomere length maintenance. AB - AIM: To evaluate telomere length in sperm DNA and its correlation with oxidative stress (normal, mild, severe). METHODS: The study included infertile men (n = 112) and age matched fertile controls (n = 102). The average telomere length from the sperm DNA was measured using a quantitative real time PCR based assay. Seminal reactive oxygen species (ROS) and 8-Isoprostane (8-IP) levels were measured by chemiluminescence assay and ELISA respectively. RESULTS: Average sperm telomere length in infertile men and controls was 0.609 +/- 0.15 and 0.789 +/- 0.060, respectively (P < 0.0001). Seminal ROS levels in infertile was higher [66.61 +/- 28.32 relative light units (RLU)/s/million sperm] than in controls (14.04 +/- 10.67 RLU/s/million sperm) (P < 0.0001). The 8-IP level in infertile men was significantly higher (421.55 +/- 131.29 pg/mL) than in controls (275.94 +/- 48.13 pg/mL) (P < 0.001). When correlated to oxidative stress, in normal range of oxidative stress (ROS, 0-21.3 RLU/s/million sperm) the average telomere length in cases was 0.663 +/- 0.14, in mild oxidative stress (ROS, 21.3-35 RLU/s/million sperm) it was elevated (0.684 +/- 0.12) and in severe oxidative stress (ROS > 35 RLU/s/million sperm) average telomere length was decreased to 0.595 +/- 0.15. CONCLUSION: Mild oxidative stress results in lengthening of telomere length, but severe oxidative stress results in shorter telomeres. Although telomere maintenance is a complex trait, the study shows that mild oxidative stress is beneficial in telomere length maintenance and thus a delicate balance needs to be established to maximize the beneficial effects of free radicals and prevent harmful effects of supra physiological levels. Detailed molecular evaluation of telomere structure, its correlation with oxidative stress would aid in elucidating the cause of accelerated telomere length attrition. PMID- 27376022 TI - Footwear modification following hallux valgus surgery: The all-or-none phenomenon. AB - AIM: To define footwear outcomes following hallux valgus surgery, focusing on patient return to comfortable and heeled footwear and patterns of post-operative footwear selection. METHODS: Surgical intervention is indicated for symptomatic cases of hallux valgus unresponsive to conservative methods, with favourable reported outcomes. The return to various types of footwear post-operatively is reflective of the degree of correction achieved, and corresponds to patient satisfaction. Patients are expected to return to comfortable footwear post operatively without significant residual symptoms. Many female patients will additionally attempt to return to high-heeled, narrow toe box shoes. However, minimal evidence exists to guide their expectations. Sixty-five female hallux valgus patients that had undergone primary surgery between 2011 and 2013 were retrospectively identified using our hospital surgical database. Patients were reviewed using a footwear-specific outcome questionnaire at a mean 18.5 mo follow up. RESULTS: Eighty-six percent of patients were able to return to comfortable footwear post-operatively with minimal discomfort. Of those intending to resume wearing heeled footwear, 62% were able to do so, with 77% of these patients wearing these as or more frequently than pre-operatively. No significant difference was observed between pre- and post-operative heel size. Mean time to return to heeled footwear was 21.4 wk post-operation. Cosmetic outcomes were very high and did not adversely impact footwear selection. CONCLUSION: We report high rates of return to both comfortable and heeled shoes in female patients following primary hallux valgus surgery. We observed an "all-or-none phenomenon" where patients rejected a return to heeled footwear unless able to tolerate them at the same frequency and heel size as pre-operatively. A minority of patients were unable to return to comfortable footwear post-operatively, which had adverse ramifications on their quality-of-life. We recommend that the importance of managing patient expectations through appropriate pre-operative counselling be emphasized in forefoot surgery. PMID- 27376023 TI - Evaluation of Superconducting Magnet Shield Configurations for Long Duration Manned Space Missions. AB - A manned mission to Mars would present an important long-term health risk to the crew members due to the prolonged exposure to the ionizing radiation of galactic cosmic-rays. The radiation levels would largely exceed those encountered in the Apollo missions. An increase in the passive shielding provided by the spacecraft implies a significant increase of the mass. The advent of superconducting magnets in the early 1960s was considered an attractive alternative. The technology allows to generate magnetic fields capable to deflect the cosmic-rays in a manner analogous to the reduction of the particle fluxes in the upper atmosphere due to the Earth's dipole magnetic field. A series of the three studies have been conducted over the last 5 years, funded successively by European Space Agency (ESA), the NASA Innovative Advanced Concepts (NIAC) program, and the Union European's Seventh Framework Programme (FP7). The shielding configurations studied are based on high-temperature superconductors, which eliminate the need to operate with liquid helium. The mass estimates of the coils and supporting structure of the engineering designs are based on the current and expected near future performance of the superconducting materials. In each case, the shield performance, in terms of dose reduction, is provided by a 3-dimensional Monte Carlo simulation, which treats in detail the electromagnetic and hadronic interactions of the galactic-cosmic rays, and the secondary particles they produce in the materials of the shield and spacecraft. A summary of the results of the studies, representing one of the most detailed and comprehensive efforts made in the field, is presented. PMID- 27376024 TI - Short DNA Fragments Are a Hallmark of Heavy Charged-Particle Irradiation and May Underlie Their Greater Therapeutic Efficacy. AB - Growing interest in proton and heavy ion therapy has reinvigorated research into the fundamental biological mechanisms underlying the therapeutic efficacy of charged-particle radiation. To improve our understanding of the greater biological effectiveness of high-LET radiations, we have investigated DNA double strand breaks (DSBs) following exposure of plasmid DNA to low-LET Co-60 gamma photon and electron irradiation and to high-LET Beryllium and Argon ions with atomic force microscopy. The sizes of DNA fragments following radiation exposure were individually measured to construct fragment size distributions from which the DSB per DNA molecule and DSB spatial distributions were derived. We report that heavy charged particles induce a significantly larger proportion of short DNA fragments in irradiated DNA molecules, reflecting densely and clustered damage patterns of high-LET energy depositions. We attribute the enhanced short DNA fragmentation following high-LET radiations as an important determinant of the observed, enhanced biological effectiveness of high-LET irradiations. PMID- 27376025 TI - Opioid-Induced Constipation among a Convenience Sample of Patients with Cancer Pain. AB - BACKGROUND: Little is known regarding the burden of opioid-induced constipation (OIC) among patients who suffer from cancer-related pain. METHODS: A prospective longitudinal study was conducted among cancer patients in the United Kingdom (UK), Canada, and Germany, which included medical record data abstraction, Internet-based patient surveys, and physician surveys. Patients on daily opioid therapy (>=30 mg for >=4 weeks) for treatment of cancer pain with self-reported OIC were recruited. Response to laxatives was defined by classifying participants into categories of laxative use and evaluating the prevalence of inadequate response. Descriptive statistics were used to evaluate outcomes, including the patient assessment of constipation-symptom (PAC-SYM), patient assessment of constipation-quality of life, EuroQOL-5 dimensions, and global assessment of treatment benefit, satisfaction, and willingness to continue. RESULTS: Recruitment was difficult for this study with only 31 participants completing the baseline survey and meeting criteria for opioid use and OIC (26 UK, 1 Canada, and 4 Germany). Fifty-two percent (n = 16) of participants were male, and all were White. Breast (23%, n = 7), pancreatic (13%, n = 4), and multiple myeloma (13%, n = 4) were the most common cancers. Mean duration of chronic pain and opioid use were 2.3 and 1.3 years, respectively. Participants reported having a mean of 4.4 bowel movements/week in the 2 weeks prior to baseline, of which a mean of 0.9 were spontaneous. Most participants (90%, n = 28) were using at least 1 lifestyle approach to manage their constipation; 65% (n = 20) were taking >=1 over-the counter laxative; 19% (n = 6) were taking >=1 prescription laxative; 23% (n = 7) reported no laxative use in the prior 2 weeks. Moderate-to-severe constipation symptoms on the PAC-SYM were common, and mean scores on health-related quality of life outcomes were comparable to chronic pain populations. CONCLUSION: In this primarily UK sample, there appears to be considerable unmet OIC treatment needs among cancer patients. PMID- 27376026 TI - Editorial: Hereditary Cancer Risk Assessment: New Perspectives and Challenges for the Next-Gen Sequencing Era. PMID- 27376027 TI - Hypothesis: The Intratumoral Immune Response against a Cancer Progenitor Cell Impacts the Development of Well-Differentiated versus Dedifferentiated Disease in Liposarcoma. AB - Well-differentiated/dedifferentiated (WD/DD) liposarcoma is a rare malignancy of adipocyte origin ("fat cancer"). Tumors may be entirely WD, WD with a DD component, or rarely DD without a clear WD component. WD tumors are low grade and generally indolent, while tumors with a DD component are high grade and behave much more aggressively, with a modest potential for distant metastasis. The presence of cancer progenitor cells in WD/DD liposarcoma is suggested by clinical evidence and reported research findings. In addition, there are emerging data to support the existence of a naturally occurring, antigen-driven, and adaptive immune response within the tumor microenvironment. We hypothesize that the intratumoral immune response is directed against a cancer progenitor cell and that the outcome of this response impacts the development of WD versus DD disease. Further study will likely provide interesting insights into the disease biology of WD/DD liposarcoma that may be readily translated to other more common cancers. PMID- 27376028 TI - Polymorphisms of Insulin-Like Growth Factor 1 Pathway Genes and Breast Cancer Risk. AB - Genetic variants of insulin-like growth factor 1 (IGF1) pathway genes have been shown to be associated with breast density and IGF1 levels and, therefore, may also influence breast cancer risk via pro-survival signaling cascades. The aim of this study was to investigate associations between IGF1 pathway single nucleotide polymorphisms (SNPs) and breast cancer risk among European and East Asian women, and potential interactions with menopausal status and breast tumor subtype. Stratified analyses of 1,037 cases and 1,050 controls from a population-based case-control study were conducted to assess associations with breast cancer for 22 SNPs across 5 IGF1 pathway genes in European and East Asian women. Odds ratios were calculated using logistic regression in additive genetic models. Polytomous logistic regression was used to assess heterogeneity by breast tumor subtype. Two SNPs of the IGF1 gene (rs1019731 and rs12821878) were associated with breast cancer risk among European women. Four highly linked IGF1 SNPs (rs2288378, rs17727841, rs7136446, and rs7956547) were modified by menopausal status among East Asian women only and associated with postmenopausal breast cancers. The association between rs2288378 and breast cancer risk was also modified by breast tumor subtype among East Asian women. Several IGF1 polymorphisms were found to be associated with breast cancer risk and some of these associations were modified by menopausal status or breast tumor subtype. Such interactions should be considered when assessing the role of these variants in breast cancer etiology. PMID- 27376029 TI - Translational Research to Improve the Efficacy of Carbon Ion Radiotherapy: Experience of Gunma University. AB - Carbon ion radiotherapy holds great promise for cancer therapy. Clinical data show that carbon ion radiotherapy is an effective treatment for tumors that are resistant to X-ray radiotherapy. Since 1994 in Japan, the National Institute of Radiological Sciences has been heading the development of carbon ion radiotherapy using the Heavy Ion Medical Accelerator in Chiba. The Gunma University Heavy Ion Medical Center (GHMC) was established in the year 2006 as a proof-of-principle institute for carbon ion radiotherapy with a view to facilitating the worldwide spread of compact accelerator systems. Along with the management of more than 1900 cancer patients to date, GHMC engages in translational research to improve the treatment efficacy of carbon ion radiotherapy. Research aimed at guiding patient selection is of utmost importance for making the most of carbon ion radiotherapy, which is an extremely limited medical resource. Intratumoral oxygen levels, radiation-induced cellular apoptosis, the capacity to repair DNA double strand breaks, and the mutational status of tumor protein p53 and epidermal growth factor receptor genes are all associated with X-ray sensitivity. Assays for these factors are useful in the identification of X-ray-resistant tumors for which carbon ion radiotherapy would be beneficial. Research aimed at optimizing treatments based on carbon ion radiotherapy is also important. This includes assessment of dose fractionation, normal tissue toxicity, tumor cell motility, and bystander effects. Furthermore, the efficacy of carbon ion radiotherapy will likely be enhanced by research into combined treatment with other modalities such as chemotherapy. Several clinically available chemotherapeutic drugs (carboplatin, paclitaxel, and etoposide) and drugs at the developmental stage (Wee-1 and heat shock protein 90 inhibitors) show a sensitizing effect on tumor cells treated with carbon ions. Additionally, the efficacy of carbon ion radiotherapy can be improved by combining it with cancer immunotherapy. Clinical validation of preclinical findings is necessary to further improve the treatment efficacy of carbon ion radiotherapy. PMID- 27376030 TI - The Emerging Role of Carbon-Ion Radiotherapy. AB - Carbon-ion radiotherapy (CIRT) has progressed rapidly in technological delivery, indications, and efficacy. Owing to a focused dose distribution in addition to high linear energy transfer and subsequently high relative biological effect, CIRT is uniquely able to target otherwise untreatable hypoxic and radioresistant disease while opening the door for substantially hypofractionated treatment of normal and radiosensitive disease. CIRT has increasingly garnered international attention and is nearing the tipping point for international adoption. PMID- 27376031 TI - The T6SSs of Pseudomonas aeruginosa Strain PAO1 and Their Effectors: Beyond Bacterial-Cell Targeting. AB - Pseudomonas aeruginosa is an opportunistic pathogen responsible for many diseases such as chronic lung colonization in cystic fibrosis patients and acute infections in hospitals. The capacity of P. aeruginosa to be pathogenic toward several hosts is notably due to different secretion systems. Amongst them, P. aeruginosa encodes three Type Six Secretion Systems (T6SS), named H1- to H3-T6SS, that act against either prokaryotes and/or eukaryotic cells. They are independent from each other and inject diverse toxins that interact with different components in the host cell. Here we summarize the roles of these T6SSs in the PAO1 strain, as well as the toxins injected and their targets. While H1-T6SS is only involved in antiprokaryotic activity through at least seven different toxins, H2-T6SS and H3-T6SS are also able to target prokaryotic as well as eukaryotic cells. Moreover, recent studies proposed that H2- and H3-T6SS have a role in epithelial cells invasion by injecting at least three different toxins. The diversity of T6SS effectors is astounding and other effectors still remain to be discovered. In this review, we present a table with other putative P. aeruginosa strain PAO1 T6SS-dependent effectors. Altogether, the T6SSs of P. aeruginosa are important systems that help fight other bacteria for their ecological niche, and are important in the pathogenicity process. PMID- 27376032 TI - Interactions "Candidatus Liberibacter solanacearum"-Bactericera cockerelli: Haplotype Effect on Vector Fitness and Gene Expression Analyses. AB - "Candidatus Liberibacter solanacearum" (Lso) has emerged as a serious threat world-wide. Five Lso haplotypes have been identified so far. Haplotypes A and B are present in the Americas and/or New Zealand, where they are vectored to solanaceous plants by the potato psyllid, Bactericera cockerelli (Sulc) (Hemiptera: Triozidae). The fastidious nature of these pathogens has hindered the study of the interactions with their eukaryotic hosts (vector and plant). To understand the strategies used by these pathogens to infect their vector, the effects of each Lso haplotype (A or B) on psyllid fitness was investigated, and genome-wide transcriptomic and RT-qPCR analyses were performed to evaluate Lso gene expression in association with its vector. Results showed that psyllids infected with haplotype B had significantly lower percentage of nymphal survival compared to psyllids infected with haplotype A. Although overall gene expression across Lso genome was similar between the two Lso haplotypes, differences in the expression of key candidate genes were found. Among the 16 putative type IV effector genes tested, four of them were differentially expressed between Lso haplotypes, while no differences in gene expression were measured by qPCR or transcriptomic analysis for the rest of the genes. This study provides new information regarding the pathogenesis of Lso haplotypes in their insect vector. PMID- 27376033 TI - Targeted CYP2E1 quantification and its correlation to currently acceptable clinical biochemical indices. AB - BACKGROUND: The Cytochrome P450 enzymes are commonly known for their major role in metabolism. Besides its metabolic role, CYP2E1 gene expression has been associated with the onset of diabetic nephropathy. CYP2E1 protein elevation has also been reported to be responsible for the production of reactive oxygen species. The aims of this study were (i) to optimize and validate a targeted proteomic approach for quantitating CYP2E1 and validating it as a suitable clinical test, (ii) to investigate the concurrency between ESI-LCMS-MS quantitated circulating CYP2E1 and gold standard indices in the context of outpatient point-of-care clinical settings involving various groups of diabetic patients and (iii) to investigate the concurrency profile of circulating CYP2E1 protein, CYP2E1 gene expression and reactive oxygen species (ROS). This is a cross sectional study involving three groups of subjects (n = 166): control, pre diabetes, and diabetes. We optimized a targeted proteomic approach for absolute quantification of CYP2E1. "YPEIEEK" and "GTVVVPTLYDNQEFPDPEK" were the representative peptides of CYP2E1 for our analytical method. Deuterated forms of "YPEIEEK" and "GTVVVPTLYDNQEFPDPEK" were used as internal standards. Lymphocytes were isolated from whole blood, microsomes were prepared, followed by in-solution digestion for production of tryptic peptides. Amounts of "YPEIEEK" and "GTVVVPTLYDNQEFPDPEK" from patients' samples were calculated from a calibration curve. RESULTS: "YPEIEEK" is a unique and reliable representative peptide for CYP2E1 quantification. "GTVVVPTLYDNQEFPDPEK" showed poor reproducibility and sensitivity. Incremental amounts of CYP2E1 protein in the peripheral circulation clearly showed concurrency with CYP2E1 gene expression and ROS levels in our study population. Elevations of CYP2E1 were observed even when gold standard clinical indicator for glycemic control (HbA1c) was within normal reference limits. Quantitated amounts of CYP2E1 protein in the pre-diabetes and diabetes groups showed significant difference relative to control group (p < 0.001). No significant differences were observed between the medians of pre-diabetes and diabetes groups (p = 0.870). CONCLUSIONS: CYP2E1 protein in peripheral blood can be reliably quantitated by the validated targeted proteomic approach method. Quantifiable amounts of CYP2E1 preceded abnormal HbA1C levels which indicates quantitation of CYP2E1 could be useful as an additional tool for early indication of diabetic risks and it complications. PMID- 27376034 TI - Illustrated Imaging Essay on Congenital Heart Diseases: Multimodality Approach Part I: Clinical Perspective, Anatomy and Imaging Techniques. AB - Rapid evolution in technology in the recent years has lead to availability of multiple options for cardiac imaging. Availability of multiple options of varying capability, poses a challenge for optimal imaging choice. While new imaging choices are added, some of the established methods find their role re-defined. State of the art imaging practices are limited to few specialist cardiac centres, depriving many radiologists and radiologist in-training of optimal exposure to the field. This presentation is aimed at providing a broad idea about complexity of clinical problem, imaging options and a large library of images of congenital heart disease. Some emphasis is made as to the need of proper balance between performing examination with technical excellence in an ideal situation against the need of the majority of patients who are investigated with less optimal resources. Cases of congenital cardiac disease are presented in an illustrative way, showing imaging appearances in multiple modalities, highlighting specific observations in given instance. PMID- 27376035 TI - Impaired endothelial function in siblings of patients with diabetic mellitus type 2. AB - BACKGROUND: Endothelial dysfunction is considered as a risk factor for cardiovascular disease, which is a consistent finding in diabetic mellitus type 2 (DMT2). First-degree relatives of DMT2 patients have a higher risk of developing DMT2 later on the life. We aimed to investigate whether impaired endothelial function exists in siblings of DMT2 patients. METHODS: As endothelial function markers, plasma E-selectin, soluble inter-cellular adhesion molecule-1 (sICAM-1), and endothelin-1 (ET-1) were measured on 27 DMT2 patients (9 m/18f; mean age: 48.48 +/- 6.75 years), 28 siblings of DMT2 patients (14 m/14f; mean age: 44.54 +/ 7.10 years), and 30 control subjects (18 m/12f; mean age: 44.72+/- 7.56 years) without any family history of diabetes. All the groups were matched by gender, age, and body mass index (BMI). RESULTS: Plasma levels of ET-1, sICAM-1, and E selectin were significantly higher in the DMT2 group compared to the control group (ET-1:0.79 +/- 1.63 pg/ml vs. 0.33 +/- 0.08 pg/ml; PCD = 0.049, sICAM-1: 71.15 +/- 27.20 ng/ml vs. 34.57 +/- 22.56 ng/ml; PCD = 0.001, E-selectin: 22.45 +/- 11.57 ng/ml vs. 16.28 +/- 7.50 ng/ml; PCD =0.026). There was a significant difference in sICAM-1 levels between siblings (62.08 +/- 26.37 ng/ml) and controls (PCS = 0.002), but not between siblings and DMT2 patients (PSD = 0.411). Moreover, a significant difference was observed in ET-1 levels between siblings (0.75 +/- 1.26 pg/ml) and controls (PCS = 0.031), but not between siblings and DMT2 patients (PSD = 0.751). There was also a significant difference in E selectin levels between DMT2 patients and siblings (16.56 +/- 8.71 ng/ml; PSD =0.028); however, the difference in E-selectin levels was not statistically significant between siblings and controls (PCS = 0.919). CONCLUSION: Endothelial function markers in the siblings of DMT2 patients are increased in comparision to the control group Therefore; family history in the DMT2 patients seems to be a risk factor for endothelial function. Furthermore, endothelial dysfunction is available very early in the DMT2 patients, even before overt hyperglycemia ensues (in siblings), and may play a key role in the etiopathology of the vasculopathy associated with DMT2. PMID- 27376036 TI - Recall for postpartum follow-up of women with gestational diabetes mellitus: Climbing a mountain. PMID- 27376037 TI - The environmental risk factors in multiple sclerosis susceptibility: A case control study. AB - BACKGROUND: Multiple sclerosis (MS) is a demyelinating and degenerating disease which involves central nervous system. Environmental risk factors have a key role in MS susceptibility. Here we aim to investigate different risk factors effect on MS susceptibility in a large population of MS patients in Isfahan, Iran. MATERIALS AND METHODS: This study is a cross-sectional hospital-based study, which was conducted on a large group of MS patients registered in Kashani hospital and a control group from normal healthy population. Demographic data, age at onset of the disease, history of viral infections, vaccination, history of trauma to head, recent stressful events, alimentation, familial history, method of delivery (caesarean section, normal vaginal delivery), disability score and history of smoking were gathered using a designed questionnaire. RESULTS: Totally 536 MS patient with the mean age of 34.37 +/- 9.22 and 399 individuals from healthy population with the mean age of 32.53 +/- 9.91 were recruited. Significant difference in history of measles infection (control = 15.5%, case = 22.4%, P = 0.009), consumption of dairy products (case = 56.6%, control = 67.5%, P = 0.01) and major stressful life events (case = 62.2%, control = 52.7%, P < 0.05) between these two groups were demonstrated. CONCLUSION: A significant relation between stress, history of infection and milk consumption was reached that highlights the importance of environmental risk factors in MS pathogenesis. PMID- 27376038 TI - Adverse effects of BCG vaccine 1173 P2 in Iran: A meta-analysis. AB - Although in the last two decades the World Health Organization (WHO) has introduced tuberculosis as "a threat to global", the vaccination with the Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the only way for the prevention of this fatal infectious disease. Despite of the efficacy of BCG vaccine especially against infants' meningitis, it has still some limitations due to a variety of adverse effects. Many studies have evaluated the side effects of different strains of BCG vaccines in different countries. In Iran, some studies have been done so far to evaluate the adverse effects of 1173 P2 strain which is used for BCG vaccination. Each of these studies have used different standardization and sampling methods. This review will survey all studies that have been published about adverse effects of 1173 P2 strain of BCG vaccine in Iran using data mining methods. PMID- 27376039 TI - Colored petri net modeling of small interfering RNA-mediated messenger RNA degradation. AB - BACKGROUND: Mathematical modeling of biological systems is an attractive way for studying complex biological systems and their behaviors. Petri Nets, due to their ability to model systems with various levels of qualitative information, have been wildly used in modeling biological systems in which enough qualitative data may not be at disposal. These nets have been used to answer questions regarding the dynamics of different cell behaviors including the translation process. In one stage of the translation process, the RNA sequence may be degraded. In the process of degradation of RNA sequence, small-noncoding RNA molecules known as small interfering RNA (siRNA) match the target RNA sequence. As a result of this matching, the target RNA sequence is destroyed. MATERIALS AND METHODS: In this context, the process of matching and destruction is modeled using Colored Petri Nets (CPNs). The model is constructed using CPNs which allow tokens to have a value or type on them. Thus, CPN is a suitable tool to model string structures in which each element of the string has a different type. Using CPNs, long RNA, and siRNA strings are modeled with a finite set of colors. The model is simulated via CPN Tools. RESULTS: A CPN model of the matching between RNA and siRNA strings is constructed in CPN Tools environment. CONCLUSION: In previous studies, a network of stoichiometric equations was modeled. However, in this particular study, we modeled the mechanism behind the silencing process. Modeling this kind of mechanisms provides us with a tool to examine the effects of different factors such as mutation or drugs on the process. PMID- 27376040 TI - ELISA reader does not interfere by mobile phone radiofrequency radiation. AB - BACKGROUND: The increasing number of mobile phones can physically cause electromagnetic interference (EMI) in medical environments; can also cause errors in immunoassays in laboratories. The ELISA readers are widely used as a useful diagnostic tool for Enzymun colorimetric assay in medicine. The aim of this study was to investigate whether the ELISA reader could be interfered by the exposure to the 900 MHz cell phones in the laboratory. MATERIALS AND METHODS: Human serum samples were collected from 14 healthy donors (9 women and 5 men) and each sample was divided into four aliquots and was placed into four batches for the in-vitro quantitative determination of human chorionic gonadotropin (hCG). During colorimetric reading of the first, second, and third batches, the ELISA reader (Stat Fax 2100, Awareness Technology, Inc., USA) was exposed to 0.5, 1.0, and 2.0 W exposure of 900 MHz radiation, respectively. For the forth batch (control group), no radiation was applied. All experiments were performed comparing ELISA read out results of the I, II, and III batches with the control batch, using the Wilcoxon test with criterion level of P = 0.050. RESULTS: The final scores in the exposed batches I, II, and III were not statistically significant relative to the control batch (P > 0.05). The results showed that 900 MHz radiation exposure did not alter the ELISA measured levels of hCG hormone in I (P = 0.219), II (P = 0.909), and III (P = 0.056) batches compared to the control batch. CONCLUSION: This study showed that ELISA reader does not interfere by mobile phone RF radiation at a closed contact (less than 5 cm distance). However, we recommend that medical institutions discuss these issues in the context of their specific use of technologies and frame a policy that is clear and straightforward to guide staff, patients, and visitors. PMID- 27376041 TI - The autonomic dysfunction in patients with lupus disease: An electrophysiological study. AB - BACKGROUND: The aim of this study was to investigate autonomic nervous system (ANS) function by using electrophysiological tests in patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: This descriptive analytical study was done on 28 individuals with a history of lupus and ten age- and sex matched healthy objects were being selected randomly. The autonomy questionnaire has been used to determine clinical symptom of ANS involvement. The electrophysiological assessments of ANS function were performed by sympathetic skin response (SSR). The mean values of sympathetic (SSR latency and amplitude) parameters were compared to determine any correlations between SSR parameters and clinical characteristics of ANS. RESULTS: 28 SLE patients (3 males, 25 females) with a mean age of 34.6 +/- 9.74 years and 10 control subjects (4 males, 6 females) with a mean age of 36.8 +/- 6.43 years were included in the study. Among patients 17 (60.7%) exhibited autonomic symptoms. Headache was the most common issue with the highest percentage rate (41.17%). The mean latency and amplitude of SSR were increased (1.52 +/- 0.16 vs. 1.39 +/- 0.16 and 107 +/- 15.6 vs. 110 +/- 15.6, respectively), compared to control. A significant difference was observed between the SSR test results of patients with lupus compared to normal healthy objects (P < 0.05). R = 0.43 correlation was found between autonomy questionnaire scores and SSR (P < 0.05). CONCLUSION: It could be concluded that latency measures in SSR test can be used as a valuable and accurate evaluation guideline for autonomic system assessment. PMID- 27376042 TI - Association between serum myeloperoxidase levels and coronary artery disease in patients without diabetes, hypertension, obesity, and hyperlipidemia. AB - BACKGROUND: Myeloperoxidase (MPO) is an enzyme, elevated in the atheroma and serum of a patient with atherosclerotic vessels. The aim of this study is to investigate whether the serum MPO level is related to the presence of plaque in patients without risk factors, such as, diabetes, hypertension, obesity, and hyperlipidemia. MATERIALS AND METHODS: A serum sample was collected from patients who referred for angiography. The MPO level was measured in the serum samples of 40 patients without risk factors for atherosclerosis using the enzyme-linked immunosorbent assay (ELISA). RESULTS: The MPO level was 245.5 +/- 13.8 (ng/ml) in patients with atherosclerosis and 213.9 +/- 8.9 (ng/ml) in patients without atherosclerosis. There was a significant difference between the groups (P = 0.002). The odds ratio was 0.67 (0.95 CI, 0.17 - 2.5) for patients with and without coronary atherosclerosis. CONCLUSION: Although the MPO concentration is higher in patients suffering from atherosclerosis, it is not a predictor of coronary artery disease in patients without diabetes, hypertension, obesity, and hyperlipidemia. PMID- 27376043 TI - Differential expression of several drug transporter genes in HepG2 and Huh-7 cell lines. AB - BACKGROUND: Cell culture techniques have many advantages for investigation of drug transport to target organ like liver. HepG2 and Huh-7 are two cell lines available from hepatoma that can be used as a model for hepatic drug transport. The present study is aimed to analyze the expression level of several drug transporter genes in two hepatoma cell lines, HepG2 and Huh-7 and their response to inhibitors. MATERIALS AND METHODS: This is an in vitro study using HepG2 and Huh-7 cells. The expression level of the following drug transporter genes was quantified: P-glycoprotein/multidrug resistance protein 1, Organic Anionic Transporter Protein 1B1 (OATP1B1) and Organic Cationic Transporter-1 (OCT1). Ribonucleic acid was extracted from the cells using Tripure isolation reagent, then gene expression level of the transporters is quantified using Applied Biosystems quantitative reverse transcriptase polymerase chain reaction. Verapamil (P-glycoprotein inhibitor), nelfinavir (OATP1B1 inhibitor), quinidine (OCT1 inhibitor) were used to differentiate the inhibitory properties of these agents to the transporter expressions in HepG2 and Huh-7 cells. RESULTS: Huh-7 shows a higher level of P-glycoprotein, OATP1B1 and OCT1 expressions compared with those of HepG2. Verapamil reduces the expressions of P-glycoprotein in HepG2 and Huh-7; nelfinavir reduces the expression of OATP1B1 in HepG2 and Huh-7; while quinidine reduces the OCT1 gene expressions in HepG2, but not in Huh-7 cells. CONCLUSION: This study indicates that HepG2 might be a more suitable in vitro model than Huh-7 to study drug transport in hepatocytes involving drug transporters. PMID- 27376044 TI - ALS1 and ALS3 gene expression and biofilm formation in Candida albicans isolated from vulvovaginal candidiasis. AB - BACKGROUND: A cluster of genes are involved in the pathogenesis and adhesion of Candida albicans to mucosa and epithelial cells in the vagina, the important of which is agglutinin-like sequence (ALS) genes. As well as vaginitis is a significant health problem among women, the antifungal resistance of Candida species is continually increasing. This cross-sectional study investigates the expression of ALS1 and ALS3 genes and biofilm formation in C. albicans isolate isolated from vaginitis. MATERIALS AND METHODS: Fifty-three recognized isolates of C. albicans were collected from women with recurrent vulvovaginal candidiasis in Iran, cultured on sabouraud dextrose agar, and then examined for gene expression. Total messenger RNA (mRNA) extracted from C. albicans isolates and complementary DNA synthesized using reverse transcriptase enzyme. Reverse transcription-polymerase chain reaction (RT-PCR) using specific primer was used to evaluate the expression of ALS1 and ALS3 through housekeeping (ACT1) genes. 3 (4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide assay was performed to assess adherence capacity and biofilm formation in the isolated. RESULTS: Forty isolates (75.8%) expressed ALS1 and 41 isolates (77.7%) expressed ALS3 gene. Moreover, 39 isolates (74%) were positive for both ALS1 and ALS3 mRNA by the RT-PCR. Adherence capability in isolates with ALS1 or ALS3 genes expression was greater than the control group (with any gene expression), besides, it was significantly for the most in the isolates that expressed both ALS1 and ALS3 genes simultaneously. CONCLUSION: The results attained indicated that there is an association between the expression of ALS1 and ALS3 genes and fluconazole resistance in C. albicans. A considerable percent of the isolates expressing the ALS1 and ALS3 genes may have contributed to their adherence to vagina and biofilm formation. PMID- 27376045 TI - The effect of angiotensin II microinjection into the bed nucleus of the stria terminalis on serum lipid peroxidation and nitric oxide metabolite levels. AB - BACKGROUND: Overactivity of renin-angiotensin system is involved in the pathophysiology of renal and cardiovascular diseases. It is suggested that endothelial cells can release nitric oxide (NO) and reactive oxygen species in response to angiotensin II (Ang II). Angiotensin type 1 (AT1) receptor of Ang II has been found in the bed nucleus of the stria terminalis (BST). BST is involved in autonomic function. This study was performed to find the role of central Ang II in serum lipid peroxidation product and in releasing NO into circulation. MATERIALS AND METHODS: Twenty-one catheterized rats were placed in stereotaxic instrument. A hole was drilled above BST. In the control group, saline 0.9% (100 nl) was microinjected into the BST. In the second group, Ang II (100 MUM, 100-150 nl) was microinjected into the BST. In the third group losartan (an AT1 antagonist) was microinjected (100 MUM, 200 nl) before Ang II into the BST. Systolic blood pressure was recorded. The NO metabolite (nitrite) and malondialdehyde (MDA) were measured in the rat's serum. RESULTS: The data indicated that microinjection of Ang II into the BST produced a pressor response (P < 0.0001). It also increased MDA and nitrite levels of the serum significantly (P < 0.001, P < 0.0001). Pretreatment with losartan before Ang II microinjection attenuated serum's levels of MDA and nitrite (P < 0.001, P < 0.0001). CONCLUSION: Our findings suggest that central effect of Ang II on blood pressure is accompanied with increased levels of MDA and nitrite in the circulation. PMID- 27376046 TI - Neurological outcome after arterial ischemic stroke in children. AB - BACKGROUND: Stroke is an important cause of disability in children. Pediatric stroke may be due to significant permanent cognitive and motor handicap in children. In this study, we evaluated long-term outcomes of stroke in pediatric patients who have been discharged with definite diagnosis of stroke in Tehran Mofid children's Hospital and Imam Hossein children's Hospital located in Isfahan, Iran, from 2005 to 2012. MATERIALS AND METHODS: A total of 53 children with stroke were included in the study. Stroke outcomes as motor disability, seizures, and cognitive dysfunctions were assessed. RESULTS: After a median follow-up of 4 years, 15 (29%) patients experienced full recovery. Thirty-eight (71%) patients had some degree of neurological handicap. CONCLUSION: Approximately 70% of children with arterial ischemic stroke suffer from long-term neurological disabilities including motor deficits, cognitive impairment, and late seizures. Stroke recurrence is the most important risk factor responsible for severe adverse neurological outcomes in pediatric stroke. PMID- 27376047 TI - Comparison of the effect of co-trimoxazole and co-trimoxazole plus ciprofloxacin in urinary tract infection prophylaxis in kidney transplant patients. AB - BACKGROUND: Urinary tract infection (UTI) as an important infection in the setting of renal transplantation carries the high mortality and morbidity rate. Thus, the prevention of this infection should receive higher priority. However, bacterial resistance to antibiotics is on the rise, with limited data to guide prophylaxis. The purpose of this study was to compare the effect of sulfamethoxazole-trimethoprim (SMZ/TMP) and SMZ/TMP plus ciprofloxacin for prophylaxis of UTI in renal transplant recipients. MATERIALS AND METHODS: In a clinical trial study, 50 patients were included and divided into two groups of 25 using block randomization. Patients in Group I received prophylactic SMZ/TMP and those in Group II received ciprofloxacin plus SMZ/TMP. The incidence of UTI in the two groups at 1, 3, and 6 months after transplantation was evaluated. This study was registered in Iranian Registry of Clinical Trial (IRCT number: IRCT 2015120823743N1). RESULTS: Of the 61 patients older than 18 years at the time of transplantation, 50 were included. UTI was documented in 8 patients (32%) in Group I and 3 (12%) in Group II (P = 0.026). The average time for the development of the first case of infection was the same for both groups (P = 0.241), and it was at its maximum in the 1(st) month. Urinary infections caused by Escherichia coli, the dominant strain, were the same in both groups (P = 0.673). CONCLUSIONS: Our study shows that the addition of 1 month course of ciprofloxacin lowered the incidence of UTI. More studies are needed to confirm the efficacy of this approach. PMID- 27376048 TI - Feasibility of establishing deletion of the late cornified envelope genes LCE3B and LCE3C as a susceptibility factor for psoriasis. AB - BACKGROUND: Psoriasis is a chronic hyperproliferative inflammatory disease of the skin, genetic predisposition to which is well-established. The late cornified envelope genes LCE3B and LCE3C are involved in maintaining the integrity of skin barrier especially following skin barrier disruption. The deletion of these genes would lead to an impaired epidermal response following damage to the skin barrier thus predisposing to psoriatic lesions. This study aimed to evaluate the common deletion of late cornified envelope genes (LCE 3B/3C) in psoriasis patients of Kashmiri ethnic population of North India. MATERIALS AND METHODS: It was a hospital-based, case-control study which included 100 psoriasis cases and an equal number of controls. Blood samples were obtained, and DNA was extracted from all the samples by a kit-based method. To determine the LCE3C_LCE3B-del genotype, a three-primer polymerase chain reaction assay was performed. RESULTS: The genotype for the common LCE3C_LCE3B deletion in 100 psoriasis patients and 100 controls was determined. Among the cases, 17 cases were homozygous for insertion genotype (I/I), 40 cases were heterozygous for insertion/deletion genotype (I/D) and 43 cases were homozygous for deletion genotype (D/D), compared to controls where 20 cases were homozygous for insertion genotype (I/I), 45 cases were heterozygous for insertion/deletion genotype (I/D), and 35 cases were homozygous for deletion genotype (D/D). The del/del frequency was higher among psoriatic patients compared to controls (43% vs. 35%) although the difference was not statistically significant (P = 0.507). CONCLUSION: We hereby infer that LCE3C_LCE3B deletion does not appear to be associated with the risk of psoriasis in our population. PMID- 27376049 TI - The role of median nerve terminal latency index in the diagnosis of carpal tunnel syndrome in comparison with other electrodiagnostic parameters. AB - BACKGROUND: Carpal tunnel syndrome (CTS) considers the most common compression neuropathy, which nerve conduction studies (NCSs) used for its detection routinely and universally. This study was performed to determine the value of the median TLI and other NCS variables and to investigate their sensitivity and specificity in the diagnosis of CTS. MATERIALS AND METHODS: The study was carried out among 100 hands of healthy volunteers and 50 hands of patients who had a positive history of paresthesia and numbness in upper extremities. Information including age, gender, and result of sensory and motor nerve conduction velocity (MNCV), peak latency difference of median and ulnar nerves of fourth digit (M4-U4 peak latency difference), and TLI were recorded for analysis. Sensitivity and specificity of electro diagnostic parameters in the diagnosis of CTS was investigated. RESULTS: Normal range of the median nerve TLI was 0.43 +/- 0.077. There was no significant difference between two groups for MNCV means (P = 0. 45). Distal sensory latency and distal motor latency (DML) of median nerve and fourth digit median-ulnar peak latency differences (PM4-PU4) for CTS group was significantly higher (P < 0.001) and mean for sensory nerve conduction velocity was significantly higher in control group (P < 0.001). The most sensitive electrophysiological finding in CTS patients was median TLI (82%), but the most specific one was DML (98%). CONCLUSION: Although in early stages of CTS, we usually expect only abnormalities in the sensory studies, but TLI may better demonstrate the effect on median nerve motor fiber even in mild cases of CTS. PMID- 27376051 TI - The Effect of Light Rail Transit on Physical Activity: Design and Methods of the Travel-Related Activity in Neighborhoods Study. AB - BACKGROUND: Use of mass transit has been proposed as a way to incorporate regular physical activity into daily life because transit use typically requires additional travel to access and depart the stop or station. If this additional travel is active, a small but potentially important amount of physical activity can be achieved daily. Although prior research has shown that transit use is associated with physical activity, important questions remain unanswered. Utilizing a major expansion of the Houston, TX, USA light-rail system as a natural experiment, the Houston Travel-Related Activity in Neighborhoods (TRAIN) Study was developed to address these unanswered questions. PURPOSE: The purpose of the TRAIN Study is to determine if the development of light-rail lines in Houston, TX, USA will prospectively affect both transit use and physical activity over 4 years. We also aim to understand how contextual effects (i.e., moderators or interaction effects), such as the neighborhood built environment and socioeconomic factors, affect the primary relations under study. METHODS: The TRAIN Study is a longitudinal cohort design, in which participants are recruited at baseline from a 3-mile buffer around each of the three new lines and measured annually four times. Recruitment is accomplished via telephone contact, ads in newspapers and advertising circulars, and targeted community outreach. Data are collected via mail and include questionnaire-assessed factors, such as perceived neighborhood characteristics, attitudes about transportation, demographics, and reported physical activity; a travel diary; and accelerometry. Additionally, field-based neighborhood audits are conducted to capture micro-scale environmental features. To assess macro-scale environmental characteristics, we utilize GIS mapping and spatial analyses. Statistical analyses will be conducted using latent growth curve modeling and discrete choice models, with a focus on identifying moderating factors (i.e., statistical interaction effects). Selection bias will be controlled via propensity score analysis. CONCLUSION: The TRAIN study is a unique opportunity to study how a multi-billion dollar investment in mass transit can simultaneously affect transportation needs and physical activity behavior. This comprehensive evaluation will provide needed evidence for policy makers, and can inform health impact assessments of future transportation projects around the world. PMID- 27376050 TI - Rediscovering Pertussis. AB - Pertussis, caused by Bordetella (B.) pertussis, a Gram-negative bacterium, is a highly contagious airway infection. Especially in infants, pertussis remains a major health concern. Acute infection with B. pertussis can cause severe illness characterized by severe respiratory failure, pulmonary hypertension, leucocytosis, and death. Over the past years, rising incidence rates of intensive care treatment in young infants were described. Due to several virulence factors (pertussis toxin, tracheal cytotoxin, adenylate cyclase toxin, filamentous hemagglutinin, and lipooligosaccharide) that promote bacterial adhesion and invasion, B. pertussis creates a unique niche for colonization within the human respiratory tract. The resulting long-term infection is mainly caused by the ability of B. pertussis to interfere with the host's innate and adaptive immune system. Although pertussis is a vaccine-preventable disease, it has persisted in vaccinated populations. Epidemiological data reported a worldwide increase in pertussis incidence among children during the past years. Either acellular pertussis (aP) vaccines or whole-cell vaccines are worldwide used. Recent studies did not detect any differences according to pertussis incidence when comparing the different vaccines used. Most of the currently used aP vaccines protect against acute infections for a period of 6-8 years. The resurgence of pertussis may be due to the lack of herd immunity caused by missing booster immunizations among adolescents and adults, low vaccine coverages in some geographic areas, and genetic changes of different B. pertussis strains. Due to the rising incidence of pertussis, probable solution strategies are discussed. Cocooning strategies (vaccination of close contact persons) and immunizations during pregnancy appear to be an approach to reduce neonatal contagiousness. During the past years, studies focused on the pathway of the immune modulation done by B. pertussis to provide a basis for the identification of new therapeutic targets to enhance the host's immune response and to probably modulate certain virulence factors. PMID- 27376052 TI - Explanatory Models of Genetics and Genetic Risk among a Selected Group of Students. AB - This exploratory qualitative study focuses on how college students conceptualize genetics and genetic risk, concepts essential for genetic literacy (GL) and genetic numeracy (GN), components of overall health literacy (HL). HL is dependent on both the background knowledge and culture of a patient, and lower HL is linked to increased morbidity and mortality for a number of chronic health conditions (e.g., diabetes and cancer). A purposive sample of 86 students from three Southwestern universities participated in eight focus groups. The sample ranged in age from 18 to 54 years, and comprised primarily of female (67.4%), single (74.4%), and non-White (57%) participants, none of whom were genetics/biology majors. A holistic-content approach revealed broad categories concerning participants' explanatory models (EMs) of genetics and genetic risk. Participants' EMs were grounded in highly contextualized narratives that only partially overlapped with biomedical models. While higher education levels should be associated with predominately knowledge-based EM of genetic risk, this study shows that even in well-educated populations cultural factors can dominate. Study findings reveal gaps in how this sample of young adults obtains, processes, and understands genetic/genomic concepts. Future studies should assess how individuals with low GL and GN obtain and process genetics and genetic risk information and incorporate this information into health decision making. Future work should also address the interaction of communication between health educators, providers, and genetic counselors, to increase patient understanding of genetic risk. PMID- 27376053 TI - Plague in Arab Maghreb, 1940-2015: A Review. AB - We reviewed the epidemiology of 49 plague outbreaks that resulted in about 7,612 cases in 30 localities in the Arabic Maghreb (Mauritania, Morocco, Algeria, Tunisia, Libya, and Egypt) over 75 years. Between 1940 and 1950, most cases recorded in Morocco (75%) and Egypt (20%), resulted from plague imported to Mediterranean harbors and transmitted by rat ectoparasites. By contrast, the re emergence of plague in the southern part of Western Sahara in 1953 and in northeast Libya in 1976 was traced to direct contact between nomadic populations and infected goats and camels in natural foci, including the consumption of contaminated meat, illustrating this neglected oral route of contamination. Further familial outbreaks were traced to human ectoparasite transmission. Efforts to identify the factors contributing to natural foci may guide where to focus the surveillance of sentinel animals in order to eradicate human plague, if not Yersinia pestis from the Arab Maghreb. PMID- 27376054 TI - Exploring the Cross-Sectional Association between Transit-Oriented Development Zoning and Active Travel and Transit Usage in the United States, 2010-2014. AB - BACKGROUND: In response to traditional zoning codes that contribute to car dependent sprawling and disconnected neighborhoods, communities are reforming their land use laws to create pedestrian-friendly areas that promote physical activity. One such reform is the adoption of transit-oriented developments or districts (TODs). TODs are higher density, compact, and mixed use areas located around transit stops that are designed to encourage walking. PURPOSE: To identify the characteristics of communities that have adopted TODs in their land use laws and examine if communities that have included TODs in their zoning codes are more likely to have adults that commute by any form of active transportation (i.e., walking, biking, or public transportation) or by using public transportation specifically. METHODS: Zoning codes effective as of 2010 were obtained for a purposeful sample of the largest 3,914 municipal jurisdictions located in 473 of the most populous U.S. counties and consolidated cities within 48 states and the District of Columbia. They were evaluated to determine whether they included TOD districts or regulations using a coding tool developed by the study team. Descriptive statistics together with t-tests and Pearson's chi-squared independence test were used to compare characteristics of jurisdictions with and without TOD zoning. Multivariate linear regressions were used to compute the adjusted association between TOD zoning and taking public or active transportation to work. RESULTS: Jurisdictions with TOD zoning were located more in the South and West than non-TOD jurisdictions and were more populous, higher income, more racially diverse, and younger. Jurisdictions with TOD zoning had significantly higher percentages of occupied housing with no vehicle than those without TOD zoning. TOD zoning was associated with significantly higher rates of public transportation to work (beta = 2.10, 95% CI = 0.88, 3.32) and active transportation to work (beta = 2.48, 95% CI = 1.03, 3.94). CONCLUSION: Communities that have or are considering developing public transit infrastructure may want to modify their zoning codes to include TODs to promote physical activity and active travel to work. PMID- 27376055 TI - Health Economics at the Crossroads of Centuries - From the Past to the Future. AB - Health economics, as an interdisciplinary science, has experienced exceptionally bold evolution through the past eight decades. Generations of committed scholars have built up huge body of knowledge and developed a set of methodological tools to assist health-care authorities with resource allocation process. Following its conception at the US National Bureau of Economic Research and Ivy League US Universities, this science has spread across the Globe. It has adapted to a myriad of local conditions and needs of the national health systems with diverse historical legacies, medical services provision, and financing patterns. Challenge of financial sustainability facing modern day health systems remains primarily attributable to population aging, prosperity diseases, large scale migrations, rapid urbanization, and technological innovation in medicine. Despite promising developments in developing countries with emerging BRICS markets on the lead, rising out-of-pocket health spending continues to threaten affordability of medical care. Universal health coverage extension will likely remain serious challenge even for some of the most advanced OECD nations. These complex circumstances create strong drivers for inevitable further development of health economics. We believe that this interdisciplinary health science shall leave long lasting blue print to be visible for decades to come. PMID- 27376056 TI - The Ebola Virus Disease Outbreak in West Africa: A Wake-up Call to Revitalize Implementation of the International Health Regulations. AB - The 2014/15 Ebola virus disease (EVD) outbreak in West Africa has highlighted the inherent weaknesses associated with the implementation of the International Health Regulations (IHR). In this perspective article, the lessons learnt from the outbreak are used to review the challenges impeding effective implementation of the IHR and to propose policy and strategic options for enhancing its application. While some progress has been achieved in implementing the IHR in several countries, numerous challenges continue to impede its effectiveness, especially in developing countries, such as those affected by the West Africa EVD outbreak. Political and economic sensitivities associated with reporting public health emergencies of international concern (PHEIC), inadequate resources (human and financial), and lack of technical know-how required for implementation of the IHR are weaknesses that continue to constrain the implementation of the regulations. In view of the complex sociopolitical, cultural, and public health dimensions of PHEICs, frameworks, such as the IHR, which have legal backing, seem to be the most effective and sustainable option for assuring timely detection, notification, and response to such events. Renewed efforts to strengthen national and global institutional frameworks for implementation of the IHR are therefore required. Improvements in transparency, commitment, and accountability of parties to the IHR, mainstreaming of the IHR into national public health governance structures, use of multidisciplinary approaches, and mobilization of the required resources for the implementation of the IHR are imperative. PMID- 27376057 TI - Accurate Prediction of the Statistics of Repetitions in Random Sequences: A Case Study in Archaea Genomes. AB - Repetitive patterns in genomic sequences have a great biological significance and also algorithmic implications. Analytic combinatorics allow to derive formula for the expected length of repetitions in a random sequence. Asymptotic results, which generalize previous works on a binary alphabet, are easily computable. Simulations on random sequences show their accuracy. As an application, the sample case of Archaea genomes illustrates how biological sequences may differ from random sequences. PMID- 27376058 TI - Lost in Translation: The Gap in Scientific Advancements and Clinical Application. AB - The evolution of medicine and medical technology hinges on the successful translation of basic science research from the bench to clinical implementation at the bedside. Out of the increasing need to facilitate the transfer of scientific knowledge to patients, translational research has emerged. Significant leaps in improving global health, such as antibiotics, vaccinations, and cancer therapies, have all seen successes under this paradigm, yet today, it has become increasingly difficult to realize this ideal scenario. As hospital revenue demand increases, and financial support declines, clinician-protected research time has been limited. Researchers, likewise, have been forced to abandon time- and resource-consuming translational research to focus on publication-generating work to maintain funding and professional advancement. Compared to the surge in scientific innovation and new fields of science, realization of transformational scientific findings in device development and materials sciences has significantly lagged behind. Herein, we describe: how the current scientific paradigm struggles in the new health-care landscape; the obstacles met by translational researchers; and solutions, both public and private, to overcoming those obstacles. We must rethink the old dogma of academia and reinvent the traditional pathways of research in order to truly impact the health-care arena and ultimately those that matter most: the patient. PMID- 27376059 TI - Submillimeter Diameter Poly(Vinyl Alcohol) Vascular Graft Patency in Rabbit Model. AB - Microvascular surgery is becoming a prevalent surgical practice. Replantation, hand reconstruction, orthopedic, and free tissue transfer procedures all rely on microvascular surgery for the repair of venous and arterial defects at the millimeter and submillimeter levels. Often, a vascular graft is required for the procedure as a means to bridge the gap between native arteries. While autologous vessels are desired for their bioactivity and non-thrombogenicity, the tedious harvest process, lack of availability, and caliber or mechanical mismatch contribute to graft failure. Thus, there is a need for an off-the-shelf artificial vascular graft that has low thrombogenic properties and mechanical properties matching those of submillimeter vessels. Poly(vinyl alcohol) hydrogel (PVA) has excellent prospects as a vascular graft due to its bioinertness, low thrombogenicity, high water content, and tunable mechanical properties. Here, we fabricated PVA grafts with submillimeter diameter and mechanical properties that closely approximated those of the rabbit femoral artery. In vitro platelet adhesion and microparticle release assay verified the low thrombogenicity of PVA. A stringent proof-of-concept in vivo test was performed by implanting PVA grafts in rabbit femoral artery with multilevel arterial occlusion. Laser Doppler measurements indicated the improved perfusion of the distal limb after implantation with PVA grafts. Moreover, ultrasound Doppler and angiography verified that the submillimeter diameter PVA vascular grafts remained patent for 2 weeks without the aid of anticoagulant or antithrombotics. Endothelial cells were observed in the luminal surface of one patent PVA graft. The advantageous non-thrombogenic and tunable mechanical properties of PVA that are retained even in the submillimeter diameter dimensions support the application of this biomaterial for vascular replacement in microvascular surgery. PMID- 27376060 TI - Biomimetic Scaffold with Aligned Microporosity Designed for Dentin Regeneration. AB - Tooth loss is a common result of a variety of oral diseases due to physiological causes, trauma, genetic disorders, and aging and can lead to physical and mental suffering that markedly lowers the individual's quality of life. Tooth is a complex organ that is composed of mineralized tissues and soft connective tissues. Dentin is the most voluminous tissue of the tooth and its formation (dentinogenesis) is a highly regulated process displaying several similarities with osteogenesis. In this study, gelatin, thermally denatured collagen, was used as a promising low-cost material to develop scaffolds for hard tissue engineering. We synthetized dentin-like scaffolds using gelatin biomineralized with magnesium-doped hydroxyapatite and blended it with alginate. With a controlled freeze-drying process and alginate cross-linking, it is possible to obtain scaffolds with microscopic aligned channels suitable for tissue engineering. 3D cell culture with mesenchymal stem cells showed the promising properties of the new scaffolds for tooth regeneration. In detail, the chemical physical features of the scaffolds, mimicking those of natural tissue, facilitate the cell adhesion, and the porosity is suitable for long-term cell colonization and fine cell-material interactions. PMID- 27376061 TI - Probing Functional Changes in Exocyst Configuration with Monoclonal Antibodies. AB - Spatial regulation of exocytosis relies on the exocyst, a hetero-octameric protein complex that tethers vesicles to fusion sites at the plasma membrane. Nevertheless, our understanding of mechanisms regulating exocyst assembly/disassembly, localization, and function are incomplete. Here, we have exploited a panel of anti-Sec6 monoclonal antibodies (mAbs) to probe possible configurational changes accompanying transitions in exocyst function in epithelial MDCK cells. Sec6 is quantitatively associated with Sec8 in high molecular weight complexes, as shown by gel filtration and co-immunoprecipitation studies. We mapped epitopes recognized by more than 20 distinct mAbs to one of six Sec6 segments. Surprisingly, mAbs that bound epitopes in each segment labeled distinct subcellular structures. In general, antibodies to epitopes in N-terminal domains labeled Sec6 in either cytosolic or nuclear pools, whereas those that bound epitopes in C-terminal domains labeled membrane-associated Sec6. In this latter group, we identified antibodies that labeled distinct Sec6 populations at the apical junctional complex, desmosomes, endoplasmic reticulum and vimentin type intermediate filaments. That each antibody was specific was verified by both Sec6 RNAi and competition with fusion proteins containing each domain. Comparison of non-polarized and polarized cells revealed that many Sec6 epitopes either redistribute or become concealed during epithelial polarization. Transitions in exocyst configurations may be regulated in part by the actions of Ral GTPases, because the exposure of Sec6 C-terminal domain epitopes at the plasma membrane is significantly reduced upon RalA RNAi. To determine whether spatio-temporal changes in epitope accessibility was correlated with differential stability of interactions between Sec6 and other exocyst subunits, we quantified relative amounts of each subunit that co-immunoprecipitated with Sec6 when antibodies to N terminal or C-terminal epitopes were used. Antibodies to Sec6NT co-precipitated substantially more Sec5, -10, -15, Exo70 and -84 than did those to Sec6CT. In contrast, antibodies to Sec6CT co-precipitated more Sec3 and Sec8 than did those to Sec6NT. These results are consistent with a model in which exocyst activation during periods of rapid membrane expansion is accompanied by molecular rearrangements within the holocomplex or association with accessory proteins, which expose the Sec6 C-terminal domain when the complex is membrane-bound and conceal it when the complex is cytoplasmic. PMID- 27376063 TI - Efficient Use of a Crude Drug/Herb Library Reveals Ephedra Herb As a Specific Antagonist for TH2-Specific Chemokine Receptors CCR3, CCR4, and CCR8. AB - Chemokine receptors CCR3 and CCR4 are preferentially expressed by TH2 cells, mast cells, and/or eosinophils, all of which are involved in the pathogenesis of allergic diseases. Therefore, CCR3 and CCR4 have long been highlighted as potent therapeutic targets for allergic diseases. Japanese traditional herbal medicine Kampo consists of multiple crude drugs/herbs, which further consist of numerous chemical substances. Recent studies have demonstrated that such chemical substances appear to promising sources in the development of novel therapeutic agents. Based on these findings, we hypothesize that Kampo-related crude drugs/herbs would contain chemical substances that inhibit the cell migration mediated by CCR3 and/or CCR4. To test this hypothesis, we screened 80 crude drugs/herbs to identify candidate substances using chemotaxis assay. Among those tested, Ephedra Herb inhibited the chemotaxis mediated by both CCR3 and CCR4, Cornus Fruit inhibited that mediated by CCR3, and Rhubarb inhibited that mediated by CCR4. Furthermore, Ephedra Herb specifically inhibited the chemotaxis mediated by not only CCR3 and CCR4 but CCR8, all of which are selectively expressed by TH2 cells. This result led us to speculate that ephedrine, a major component of Ephedra Herb, would play a central role in the inhibitory effects on the chemotaxis mediated by CCR3, CCR4, and CCR8. However, ephedrine exhibited little effects on the chemotaxis. Therefore, we fractionated Ephedra Herb into four subfractions and examined the inhibitory effects of each subfraction. As the results, ethyl acetate-insoluble fraction exhibited the inhibitory effects on chemotaxis and calcium mobilization mediated by CCR3 and CCR4 most significantly. In contrast, chloroform-soluble fraction exhibited a weak inhibitory effect on the chemotaxis mediated by CCR8. Furthermore, maoto, one of the Kampo formulations containing Ephedra Herb, exhibited the inhibitory effects on the chemotaxis mediated by CCR3, CCR4, and CCR8. Taken together, our data suggest that these crude drugs/herbs might be useful sources to develop new drugs targeting TH2-mediated allergic diseases. PMID- 27376062 TI - ERK1 and ERK2 Map Kinases: Specific Roles or Functional Redundancy? AB - The MAP kinase signaling cascade Ras/Raf/MEK/ERK has been involved in a large variety of cellular and physiological processes that are crucial for life. Many pathological situations have been associated to this pathway. More than one isoform has been described at each level of the cascade. In this review we devoted our attention to ERK1 and ERK2, which are the effector kinases of the pathway. Whether ERK1 and ERK2 specify functional differences or are in contrast functionally redundant, constitutes an ongoing debate despite the huge amount of studies performed to date. In this review we compiled data on ERK1 vs. ERK2 gene structures, protein sequences, expression levels, structural and molecular mechanisms of activation and substrate recognition. We have also attempted to perform a rigorous analysis of studies regarding the individual roles of ERK1 and ERK2 by the means of morpholinos, siRNA, and shRNA silencing as well as gene disruption or gene replacement in mice. Finally, we comment on a recent study of gene and protein evolution of ERK isoforms as a distinct approach to address the same question. Our review permits the evaluation of the relevance of published studies in the field especially when measurements of global ERK activation are taken into account. Our analysis favors the hypothesis of ERK1 and ERK2 exhibiting functional redundancy and points to the concept of the global ERK quantity, and not isoform specificity, as being the essential determinant to achieve ERK function. PMID- 27376064 TI - Focal Targeting of the Bacterial Envelope by Antimicrobial Peptides. AB - Antimicrobial peptides (AMPs) are utilized by both eukaryotic and prokaryotic organisms. AMPs such as the human beta defensins, human neutrophil peptides, human cathelicidin, and many bacterial bacteriocins are cationic and capable of binding to anionic regions of the bacterial surface. Cationic AMPs (CAMPs) target anionic lipids [e.g., phosphatidylglycerol (PG) and cardiolipins (CL)] in the cell membrane and anionic components [e.g., lipopolysaccharide (LPS) and lipoteichoic acid (LTA)] of the cell envelope. Bacteria have evolved mechanisms to modify these same targets in order to resist CAMP killing, e.g., lysinylation of PG to yield cationic lysyl-PG and alanylation of LTA. Since CAMPs offer a promising therapeutic alternative to conventional antibiotics, which are becoming less effective due to rapidly emerging antibiotic resistance, there is a strong need to improve our understanding about the AMP mechanism of action. Recent literature suggests that AMPs often interact with the bacterial cell envelope at discrete foci. Here we review recent AMP literature, with an emphasis on focal interactions with bacteria, including (1) CAMP disruption mechanisms, (2) delocalization of membrane proteins and lipids by CAMPs, and (3) CAMP sensing systems and resistance mechanisms. We conclude with new approaches for studying the bacterial membrane, e.g., lipidomics, high resolution imaging, and non detergent-based membrane domain extraction. PMID- 27376065 TI - Emerging Roles of the Mitogen and Stress Activated Kinases MSK1 and MSK2. AB - Mitogen- and stress-activated kinases (MSK) 1 and 2 are nuclear proteins activated downstream of the ERK1/2 or p38 MAPK pathways. MSKs phosphorylate multiple substrates, including CREB and Histone H3, and their major role is the regulation of specific subsets of Immediate Early genes (IEG). While MSKs are expressed in multiple tissues, their levels are high in immune and neuronal cells and it is in these systems most is known about their function. In immunity, MSKs have predominantly anti-inflammatory roles and help regulate production of the anti-inflammatory cytokine IL-10. In the CNS they are implicated in neuronal proliferation and synaptic plasticity. In this review we will focus on recent advances in understanding the roles of MSKs in the innate immune system and neuronal function. PMID- 27376066 TI - Pulmonary Hypertension and Indicators of Right Ventricular Function. AB - Pulmonary hypertension (PH) is a rare disease, whose underlying mechanisms are not fully understood. It is characterized by pulmonary arterial vasoconstriction and vessels wall thickening, mainly intimal and medial layers. Several molecular pathways have been studied, but their respective roles remain unknown. Cardiac repercussions of PH are hypertrophy, dilation, and progressive right ventricular dysfunction. Multiple echocardiographic parameters are being used, in order to assess anatomy and cardiac function, but there are no guidelines edited about their usefulness. Thus, it is now recommended to associate the best-known parameters, such as atrial and ventricular diameters or tricuspid annular plane systolic excursion. Cardiac catheterization remains necessary to establish the diagnosis of PH and to assess pulmonary hemodynamic state. Concerning energetic metabolism, free fatty acids, normally used to provide energy for myocardial contraction, are replaced by glucose uptake. These abnormalities are illustrated by increased (18)F-fluorodeoxyglucose ((18)F-FDG) uptake on positron emission tomography/computed tomography, which seems to be correlated with echocardiographic and hemodynamic parameters. PMID- 27376067 TI - Enabled or Disabled: Is the Environment Right for Using Biodiversity to Improve Nutrition? AB - How can we ensure that 9 billion people will have access to a nutritious and healthy diet that is produced in a sustainable manner by 2050? Despite major advances, our global food system still fails to feed a significant part of humanity adequately. Diversifying food systems and diets to include nutrient-rich species can help reduce malnutrition, while contributing other multiple benefits including healthy ecosystems. While research continues to demonstrate the value of incorporating biodiversity into food systems and diets, perverse subsidies, and barriers often prevent this. Countries like Brazil have shown that, by strategic actions and interventions, it is indeed possible to create better contexts to mainstream biodiversity for improved nutrition into government programs and public policies. Despite some progress, there are few global and national policy mechanisms or processes that effectively join biodiversity with agriculture and nutrition efforts. This perspective paper discusses the benefits of biodiversity for nutrition and explores what an enabling environment for biodiversity to improve nutrition might look like, including examples of steps and actions from a multi-country project that other countries might replicate. Finally, we suggest what it might take to create enabling environments to mainstream biodiversity into global initiatives and national programs and policies on food and nutrition security. With demand for new thinking about how we improve agriculture for nutrition and growing international recognition of the role biodiversity, the 2030 Agenda for Sustainable Development presents an opportunity to move beyond business-as-usual to more holistic approaches to food and nutrition security. PMID- 27376068 TI - Independent and Combined Effects of Lactitol, Polydextrose, and Bacteroides thetaiotaomicron on Postprandial Metabolism and Body Weight in Rats Fed a High Fat Diet. AB - Obesity is related to the consumption of energy-dense foods in addition to changes in the microbiome where a higher abundance of gut Bacteroidetes can be found in lean subjects or after weight loss. Lactitol, a sweet-tasting sugar alcohol, is a common sugar-replacement in foods. Polydextrose (PDX), a highly branched glucose polymer, is known to reduce energy intake. Here, we test if the combined effects of lactitol or PDX in combination with Bacteroides species will have a beneficial metabolic response in rats fed a high-fat (HF) diet. A total of 175 male Wistar rats were fed either a LF or HF diet. Bacteroides thetaiotaomicron (10(10) bacteria/animal/day) was orally administered with or without lactitol (1.6-2 g/animal/day) or PDX (2 g/animal/day) for 8 days. Postprandial blood samples, cecal digesta, and feces were collected on the last day. Measurements included: body weight, feed consumption, cecal short-chain fatty acids, fecal dry matter and heat value, blood glucose, insulin, triglyceride, and satiety hormone concentrations. Lactitol and PDX decreased the mean body weight when administered with B. thetaiotaomicron or when lactitol was administered alone. Levels of postprandial plasma triglycerides declined with lactitol and PDX when administered with B. thetaiotaomicron. For intestinal hormone release, lactitol - alone or with B. thetaiotaomicron - increased the release of gastrointestinal peptide tyrosine tyrosine (PYY) as well as the area under the curve (AUC) measured for PYY (0-8 h). In addition, levels of insulin AUC (0-8 h) decreased in the lactitol and PDX-supplemented groups. Lactitol and PDX may both provide additional means to regulate postprandial metabolism and weight management, whereas the addition of B. thetaiotaomicron in the tested doses had only minor effects on the measured parameters. PMID- 27376069 TI - Gender Role Orientation with Health Literacy and Self-Efficacy for Healthy Eating among Japanese Workers in Early Adulthood. AB - Gender role, independent of biological sex, affects health. However, research on healthy eating that considers the importance of gender norms is scarce. People who are androgynous and have high masculinity and femininity are reported to have better health practices than other people. The present study aimed to examine the differences in health literacy (HL) and self-efficacy for healthy eating by gender role in Japanese men and women. Participants were 629 men and women aged 25-34 years, recruited via a Japanese Internet research company database. Participants were categorized into four gender role groups using the Japanese Gender Role Index. HL and self-efficacy for healthy eating were assessed using the healthy eating literacy (HEL) scale and the healthy eating and weight self efficacy (HEWSE) scale. Analysis of variance with Bonferroni-adjusted post hoc tests and hierarchical multiple regression were used to test the research hypotheses. We found that the Androgynous group had significantly higher HEL and HEWSE scores than the Feminine and Undifferentiated groups. The Masculine group scored significantly higher on both measures than the Undifferentiated group. Being Androgynous (HEL: beta = 0.34, p < 0.001; HEWSE: beta = 0.30, p < 0.001) was a strong predictor for higher scores even after considering other predictors. The results showed significant associations between gender role orientation and individual HL and self-efficacy for healthy eating. These findings may be relevant for promoting healthy eating from the perspective of gender norms. PMID- 27376072 TI - The Grand Challenge of Characterizing Ribonucleoprotein Networks. PMID- 27376071 TI - A Novel and Fast Purification Method for Nucleoside Transporters. AB - Nucleoside transporters (NTs) play critical biological roles in humans, and to understand the molecular mechanism of nucleoside transport requires high resolution structural information. However, the main bottleneck for structural analysis of NTs is the production of pure, stable, and high quality native protein for crystallization trials. Here we report a novel membrane protein expression and purification strategy, including construction of a high-yield membrane protein expression vector, and a new and fast purification protocol for NTs. The advantages of this strategy are the improved time efficiency, leading to high quality, active, stable membrane proteins, and the efficient use of reagents and consumables. Our strategy might serve as a useful point of reference for investigating NTs and other membrane proteins by clarifying the technical points of vector construction and improvements of membrane protein expression and purification. PMID- 27376070 TI - Increased Hydration Can Be Associated with Weight Loss. AB - This mini-review develops the hypothesis that increased hydration leads to body weight loss, mainly through a decrease in feeding, and a loss of fat, through increased lipolysis. The publications cited come from animal, mainly rodent, studies where manipulations of the central and/or the peripheral renin angiotensin system lead to an increased drinking response and a decrease in body weight. This hypothesis derives from a broader association between chronic hypohydration (extracellular dehydration) and raised levels of the hormone angiotensin II (AngII) associated with many chronic diseases, such as obesity, diabetes, cancer, and cardiovascular disease. Proposed mechanisms to explain these effects involve an increase in metabolism due to hydration expanding cell volume. The results of these animal studies often can be applied to the humans. Human studies are consistent with this hypothesis for weight loss and for reducing the risk factors in the development of obesity and type 2 diabetes. PMID- 27376073 TI - Multivariate Methods for Genetic Variants Selection and Risk Prediction in Cardiovascular Diseases. AB - Over the last decade, high-throughput genotyping and sequencing technologies have contributed to major advancements in genetics research, as these technologies now facilitate affordable mapping of the entire genome for large sets of individuals. Given this, genome-wide association studies are proving to be powerful tools in identifying genetic variants that have the capacity to modify the probability of developing a disease or trait of interest. However, when the study's goal is to evaluate the effect of the presence of genetic variants mapping to specific chromosomes regions on a specific phenotype, the candidate loci approach is still preferred. Regardless of which approach is taken, such a large data set calls for the establishment and development of appropriate analytical methods in order to translate such knowledge into biological or clinical findings. Standard univariate tests often fail to identify informative genetic variants, especially when dealing with complex traits, which are more likely to result from a combination of rare and common variants and non-genetic determinants. These limitations can partially be overcome by multivariate methods, which allow for the identification of informative combinations of genetic variants and non genetic features. Furthermore, such methods can help to generate additive genetic scores and risk stratification algorithms that, once extensively validated in independent cohorts, could serve as useful tools to assist clinicians in decision making. This review aims to provide readers with an overview of the main multivariate methods for genetic data analysis that could be applied to the analysis of cardiovascular traits. PMID- 27376074 TI - Molecular and Genetic Insights into Thoracic Aortic Dilation in Conotruncal Heart Defects. AB - Thoracic aortic dilation (AD) has commonly been described in conotruncal defects (CTDs), such as tetralogy of Fallot, double outlet right ventricle and transposition of the great arteries, and truncus arteriosus. Several theories for this have been devised, but fairly recent data indicate that there is likely an underlying histologic abnormality, similar to that seen in Marfan and other connective tissue disease. The majority of aortic dissection in the general population occurs after the age of 45 years, and there have been very few case reports of aortic dissection in CTD. Given advances in cardiac surgery and increasing survival over the past several decades, there has been rising concern that, as patients who have survived surgical correction of these defects age, there may be increased morbidity and mortality due to aortic dissection and aortic regurgitation. This review discusses the most recent developments in research into AD in CTD, including associated genetic mutations. PMID- 27376075 TI - 18F-FDG Positron Emission Tomography - An Innovative Technique for the Diagnosis of a Canine Lameness. AB - INTRODUCTION: Positron emission tomography (PET) imaging with fluorine-18 fluorodeoxyglucose (18F-FDG) is widely known for its use in the diagnosis and tracking of primary and metastatic tumors via uptake and retention of the radiopharmaceutical by hypermetabolic cells. 18F-FDG is also used to study the normal physiology of glucose uptake, metabolism, and muscle activity during and after exercise. BACKGROUND: A pilot study adding PET imaging to the diagnostic evaluation of canine patients undergoing computed tomography (CT) for mild or intermittent thoracic and pelvic limb lameness is ongoing. Dogs with an observable (grade 1-2/5) lameness that have undergone routine radiography and complete physical examination by board-certified veterinary surgeons and sports medicine and rehabilitation specialists are enrolled. Each patient undergoes leash walking for 15 min prior to premedication and induction of general anesthesia for the PET-CT examination. 18F-FDG is injected intravenously, and a whole-body PET examination is conducted after 1 h of radiopharmaceutical uptake time. Standard algorithm, whole-body pre- and post-contrast CT examinations, and focused, standard, and bone algorithm CT scans of the thoracic or pelvic limb areas of interest are obtained concurrently. Abnormal PET-CT findings are further investigated with additional diagnostic imaging or at surgery (e.g., ultrasound, MRI, and arthroscopy). DISCUSSION: This case report uses a canine patient referred for thoracic limb lameness to illustrate the role of advanced imaging in a diagnostic plan and to discuss a recommended PET-CT procedure for lameness evaluation. The PET-CT imaging protocol recommended in this report was designed to significantly enhance a routine thoracic limb CT examination and to identify areas of muscle, tendon, or ligament overuse, inflammation, or injury for further diagnostic procedures or definitive treatment. CONCLUDING REMARKS: 18F-FDG PET-CT adds valuable physiologic and anatomic information to the diagnostic evaluation of patients presenting with indistinct or intermittent clinical signs of musculoskeletal inflammation or injury. In addition, tailoring the PET acquisition and radiopharmaceutical parameters allows for detailed information gathering to more closely assess normal and abnormal physiology, unlocking a new frontier in the study of canine athletic injury and optimal performance. PMID- 27376076 TI - Integrating Genomic Data Sets for Knowledge Discovery: An Informed Approach to Management of Captive Endangered Species. AB - Many endangered captive populations exhibit reduced genetic diversity resulting in health issues that impact reproductive fitness and quality of life. Numerous cost effective genomic sequencing and genotyping technologies provide unparalleled opportunity for incorporating genomics knowledge in management of endangered species. Genomic data, such as sequence data, transcriptome data, and genotyping data, provide critical information about a captive population that, when leveraged correctly, can be utilized to maximize population genetic variation while simultaneously reducing unintended introduction or propagation of undesirable phenotypes. Current approaches aimed at managing endangered captive populations utilize species survival plans (SSPs) that rely upon mean kinship estimates to maximize genetic diversity while simultaneously avoiding artificial selection in the breeding program. However, as genomic resources increase for each endangered species, the potential knowledge available for management also increases. Unlike model organisms in which considerable scientific resources are used to experimentally validate genotype-phenotype relationships, endangered species typically lack the necessary sample sizes and economic resources required for such studies. Even so, in the absence of experimentally verified genetic discoveries, genomics data still provides value. In fact, bioinformatics and comparative genomics approaches offer mechanisms for translating these raw genomics data sets into integrated knowledge that enable an informed approach to endangered species management. PMID- 27376077 TI - De Novo Assembly and Comparative Transcriptome Analysis Provide Insight into Lysine Biosynthesis in Toona sinensis Roem. AB - Toona sinensis Roem is a popular leafy vegetable in Chinese cuisine and is also used as a traditional Chinese medicine. In this study, leaf samples were collected from the same plant on two development stages and then used for high throughput Illumina RNA-sequencing (RNA-Seq). 125,884 transcripts and 54,628 unigenes were obtained through de novo assembly. A total of 25,570 could be annotated with known biological functions, which indicated that the T. sinensis leaves and shoots were undergoing multiple developmental processes especially for active metabolic processes. Analysis of differentially expressed unigenes between the two libraries showed that the lysine biosynthesis was an enriched KEGG pathway, and candidate genes involved in the lysine biosynthesis pathway in T. sinensis leaves and shoots were identified. Our results provide a primary analysis of the gene expression files of T. sinensis leaf and shoot on different development stages and afford a valuable resource for genetic and genomic research on plant lysine biosynthesis. PMID- 27376078 TI - Biosensor for Hepatocellular Injury Corresponds to Experimental Scoring of Hepatosplenic Schistosomiasis in Mice. AB - Severe hepatosplenic injury of mansonian schistosomiasis is caused by Th2 mediated granulomatous response against parasite eggs entrapped within the periportal tissue. Subsequent fibrotic scarring and deformation/sclerosing of intrahepatic portal veins lead to portal hypertension, ascites, and oesophageal varices. The murine model of Schistosoma mansoni (S. mansoni) infection is suitable to establish the severe hepatosplenic injury of disease within a reasonable time scale for the development of novel antifibrotic or anti-infective strategies against S. mansoni infection. The drawback of the murine model is that the material prepared for complex analysis of egg burden, granuloma size, hepatic inflammation, and fibrosis is limited due to small amounts of liver tissue and blood samples. The objective of our study was the implementation of a macroscopic scoring system for mice livers to determine infection-related organ alterations of S. mansoni infection. In addition, an in vitro biosensor system based on the detection of hepatocellular injury in HepG2/C3A cells following incubation with serum of moderately (50 S. mansoni cercariae) and heavily (100 S. mansoni cercariae) infected mice affirmed the value of our scoring system. Therefore, our score represents a valuable tool in experimental schistosomiasis to assess severity of hepatosplenic schistosomiasis and reduce animal numbers by saving precious tissue samples. PMID- 27376079 TI - Microchips in Medicine: Current and Future Applications. AB - With the objective of improving efficacy and morbidity, device manufacturers incorporate chemicals or drugs into medical implants. Using multiple reservoirs of discrete drug doses, microchips represent a new technology capable of on demand release of various drugs over long periods of time. Herein, we review drug delivery systems, how microchips work, recent investigations, and future applications in various fields of medicine. PMID- 27376080 TI - The Hearing Outcomes of Cochlear Implantation in Waardenburg Syndrome. AB - Objectives. This study aimed to determine the feasibility of cochlear implantation for sensorineural hearing loss in patients with Waardenburg syndrome. Method. A retrospective chart review was performed on patients who underwent cochlear implantation at the University of Tokyo Hospital. Clinical classification, genetic mutation, clinical course, preoperative hearing threshold, high-resolution computed tomography of the temporal bone, and postoperative hearing outcome were assessed. Result. Five children with Waardenburg syndrome underwent cochlear implantation. The average age at implantation was 2 years 11 months (ranging from 1 year 9 months to 6 years 3 months). Four patients had congenital profound hearing loss and one patient had progressive hearing loss. Two patients had an inner ear malformation of cochlear incomplete partition type 2. No surgical complication or difficulty was seen in any patient. All patients showed good hearing outcome postoperatively. Conclusion. Cochlear implantation could be a good treatment option for Waardenburg syndrome. PMID- 27376081 TI - High b-Value Diffusion MRI to Differentiate Recurrent Tumors from Posttreatment Changes in Head and Neck Squamous Cell Carcinoma: A Single Center Prospective Study. AB - Recently DW-MR Imaging has shown promising results in distinguishing between recurrent tumors and posttreatment changes in Head and Neck Squamous Cell Carcinoma (HNSSC). Aim of this study was to evaluate the diagnostic performances of DWI at high b-value (b = 2000 s/mm(2)) compared to standard b-value (b = 1000 s/mm(2)) and ADCratio values (ADCratio = ADC2000/ADC1000 * 100) to differentiate recurrent tumors from posttreatment changes after treatment of HSNCC. 20 patients (16 M, 4 F) underwent MR Imaging between 2 and 16 months (mean 7) after treatment. Besides morphological sequences, we performed single-shot echo-planar DWI at b = 1000 s/mm(2) and b = 2000 s/mm(2), and corresponding ADC maps were generated (ADC1000 and ADC2000, resp.). By considering contrast-enhanced T1 weighted images as references, ROIs were drawn in order to evaluate mean ADC1000, ADC2000, and ADCratio. The mean ADC1000 and ADC2000 in recurrent tumors were significantly lower than those in posttreatment changes (P = 0.001 and P = 0.016, resp.). Moreover, the mean ADCratio between the two groups showed a statistically significant difference (P = 0.002). Sensitivity, specificity, and accuracy of ADCratio were 82.0%, 100%, and 90%, respectively, by considering an optimal cutoff value of 65.5%. ADCratio is a promising value to differentiate between recurrent tumors and posttreatment changes in HNSCC and may be more useful than ADC1000 and ADC2000. PMID- 27376082 TI - Role of Autophagy and Apoptosis in the Postinfluenza Bacterial Pneumonia. AB - The risk of influenza A virus (IAV) is more likely caused by secondary bacterial infections. During the past decades, a great amount of studies have been conducted on increased morbidity from secondary bacterial infections following influenza and provide an increasing number of explanations for the mechanisms underlying the infections. In this paper, we first review the recent research progress that IAV infection increased susceptibility to bacterial infection. We then propose an assumption that autophagy and apoptosis manipulation are beneficial to antagonize post-IAV bacterial infection and discuss the clinical significance. PMID- 27376083 TI - Hospital Mortality in the United States following Acute Kidney Injury. AB - Acute kidney injury (AKI) is a common reason for hospital admission and complication of many inpatient procedures. The temporal incidence of AKI and the association of AKI admissions with in-hospital mortality are a growing problem in the world today. In this review, we discuss the epidemiology of AKI and its association with in-hospital mortality in the United States. AKI has been growing at a rate of 14% per year since 2001. However, the in-hospital mortality associated with AKI has been on the decline starting with 21.9% in 2001 to 9.1 in 2011, even though the number of AKI-related in-hospital deaths increased almost twofold from 147,943 to 285,768 deaths. We discuss the importance of the 71% reduction in AKI-related mortality among hospitalized patients in the United States and draw on the discussion of whether or not this is a phenomenon of hospital billing (coding) or improvements to the management of AKI. PMID- 27376084 TI - Safety Irradiation Parameters of Nd:YAP Laser Beam for Endodontic Treatments: An In Vitro Study. AB - Objective. Nd:YAP laser has several potentialities of clinical applications in endodontics. The aim of our study is to determine the safety range of irradiation parameters during endodontic application of Nd:YAP laser that can be used without damaging and overheating the periodontal tissue. Material and Methods. Twenty seven caries-free single-rooted extracted human teeth were used. Crowns were sectioned to obtain 11 mm root canal length. Temperature increases at root surfaces were measured by a thermocouple during Nd:YAP laser irradiation of root canals at different energy densities. Canal irradiation was accomplished with a circular and retrograde movement from the apex until the cervical part of the canal during 10 seconds with an axial speed of 1 mm/s. Each irradiation was done in a canal irrigated continuously with 2.25% NaOCl solution. Results. Periodontal temperature increase depends on the value of energy density. Means and standard deviations of temperature increases at root surfaces were below 10 degrees C (safe threshold level) when the average energy densities delivered per second were equal to or below 4981 J/cm(2) and 9554 J/cm(2), respectively, for irradiations using a fiber diameter of 320 MUm and 200 MUm. Conclusions. Within the limitations of this study and under specific irradiation conditions, Nd:YAP laser beam may be considered harmless for periodontal tissues during endodontic applications. PMID- 27376085 TI - Evaluation of Culture Conditions to Obtain Fatty Acids from Saline Microalgae Species: Dunaliella salina, Sinecosyfis sp., and Chroomonas sp. AB - The use of the saline microalgae, Dunaliella salina, Sinecosyfis sp., and Chroomonas sp., was explored as an alternative source for the production of fatty acids using fertilizer and glycerol as culture media. The nutrient medium used contained "Nutrifoliar," a commercial fertilizer, and/or glycerol, in natural sea water. The microalgae were placed in cultures with different conditions. The parameters that favored the largest production of fatty acids were 24 hours of agitation and illumination, 1620 L/day of air supply, 2.25 L of air/min, and a temperature of 32 degrees C using "Nutrifoliar" as the culture media. Results indicated that, from 3 g of microalgae in wet base of Chroomonas sp., 54.43 mg of oil was produced. The chromatographic characterization of oil obtained revealed the presence of essential fatty acids such as 9,12,15-octadecatrienoic acid (omega-3) and 4,7,10-hexadecatrienoic acid (omega-6) from the species Dunaliella salina. On the other hand, 9,12-octadecadienoic acid (omega-6) and cis-11 eicosenoic acid (omega-9) were identified from the species Chroomonas sp. The temperature variations played an important role in the velocity of growth or the production of the algae biomass, the amount of oil, and the ability to produce fatty acids. PMID- 27376086 TI - Molecular Background of miRNA Role in Asthma and COPD: An Updated Insight. AB - Inflammatory airway diseases are a significant health problems requiring new approaches to the existing therapies and addressing fundamental issues. Difficulties in developing effective therapeutic strategies might be caused by lack of understanding of their exact molecular mechanism. MicroRNAs (miRNAs) are a class of regulators that already revolutionized the view of gene expression regulation. A cumulating number of investigations show a pivotal role of miRNAs in the pathogenesis of asthma, chronic obstructive pulmonary disease (COPD), or airway remodeling through the regulation of many pathways involved in their pathogenesis. Expression changes of several miRNAs have also been found to play a role in the development and/or improvement in asthma or COPD. Still, relatively little is known about the role of miRNAs in inflammatory disorders. The microRNA profiles may differ depending on the cell type or antigen-presenting cell. Based on the newest literature, this review discusses the current knowledge concerning miRNA contribution and influence on lung inflammation and chosen inflammatory airway diseases: asthma and COPD. PMID- 27376087 TI - Mathematical Based Calculation of Drug Penetration Depth in Solid Tumors. AB - Cancer is a class of diseases characterized by out-of-control cells' growth which affect cells and make them damaged. Many treatment options for cancer exist. Chemotherapy as an important treatment option is the use of drugs to treat cancer. The anticancer drug travels to the tumor and then diffuses in it through capillaries. The diffusion of drugs in the solid tumor is limited by penetration depth which is different in case of different drugs and cancers. The computation of this depth is important as it helps physicians to investigate about treatment of infected tissue. Although many efforts have been made on studying and measuring drug penetration depth, less works have been done on computing this length from a mathematical point of view. In this paper, first we propose phase lagging model for diffusion of drug in the tumor. Then, using this model on one side and considering the classic diffusion on the other side, we compute the drug penetration depth in the solid tumor. This computed value of drug penetration depth is corroborated by comparison with the values measured by experiments. PMID- 27376088 TI - A Comparative Study of Land Cover Classification by Using Multispectral and Texture Data. AB - The main objective of this study is to find out the importance of machine vision approach for the classification of five types of land cover data such as bare land, desert rangeland, green pasture, fertile cultivated land, and Sutlej river land. A novel spectra-statistical framework is designed to classify the subjective land cover data types accurately. Multispectral data of these land covers were acquired by using a handheld device named multispectral radiometer in the form of five spectral bands (blue, green, red, near infrared, and shortwave infrared) while texture data were acquired with a digital camera by the transformation of acquired images into 229 texture features for each image. The most discriminant 30 features of each image were obtained by integrating the three statistical features selection techniques such as Fisher, Probability of Error plus Average Correlation, and Mutual Information (F + PA + MI). Selected texture data clustering was verified by nonlinear discriminant analysis while linear discriminant analysis approach was applied for multispectral data. For classification, the texture and multispectral data were deployed to artificial neural network (ANN: n-class). By implementing a cross validation method (80-20), we received an accuracy of 91.332% for texture data and 96.40% for multispectral data, respectively. PMID- 27376089 TI - The Role of Hyperglycemia and Insulin Resistance in the Development and Progression of Pulmonary Arterial Hypertension. AB - Pulmonary hypertension is a progressive disorder which often leads to right ventricular failure and death. While the existing classification system for pulmonary hypertension does not account for the impact of diabetes mellitus, evidence is emerging that suggests that diabetes is associated with pulmonary hypertension and that diabetes modifies the course of pulmonary hypertension. There is also growing radiographic, hemodynamic, biochemical, and pathologic data supporting an association between diabetes and pulmonary hypertension. More robust epidemiologic studies are needed to confirm an association between diabetes and pulmonary hypertension and to show that diabetes is a disease modifier in pulmonary hypertension. In addition, evaluating the effects of glucose control in animals with pulmonary hypertension and diabetes (as well as in humans) is warranted. PMID- 27376091 TI - Monocyte Differentiation towards Protumor Activity Does Not Correlate with M1 or M2 Phenotypes. AB - Macrophages facilitate breast cancer progression. Macrophages were initially classified as M1 or M2 based on their distinct metabolic programs and then expanded to include antitumoral (M1) and protumoral (M2) activities. However, it is still uncertain what markers define the pro- and antitumoral phenotypes and what conditions lead to their formation. In this study, monocytic cell lines and primary monocytes were subjected to commonly reported protocols of M1/M2 polarization and conditions known to engage monocytes into protumoral functions. The results showed that only IDO enzyme and CD86 M1 markers were upregulated correlating with M1 polarization. TNF-alpha, CCR7, IL-10, arginase I, CD36, and CD163 were expressed indistinguishably from M1 or M2 polarization. Similarly, protumoral engaging resulted in upregulation of both M1 and M2 markers, with conditioned media from the most aggressive breast cancer cell line promoting the greatest changes. In spite of the mixed phenotype, M1-polarized macrophages exhibited the highest expression/secretion of inflammatory mediators, many of which have previously been associated with breast cancer aggressiveness. These data argue that although the existence of protumoral macrophages is unquestionable, their associated phenotypes and the precise conditions driving their formation are still unclear, and those conditions may need both M1 and M2 stimuli. PMID- 27376092 TI - Using the laws of thermodynamics to understand how matrix metalloproteinases coordinate the myocardial response to injury. AB - Following myocardial infarction (MI), the left ventricle (LV) undergoes a series of molecular, cellular, and functional alterations that are both part of the wound healing response to form a scar in the infarct region and the consequence of that response. Using the laws of thermodynamics as an analogy, we present here three laws for categorizing the post-MI LV remodeling process. The first law is that the LV will attempt to maintain equilibrium and compensate as a way to maximize function, the second law is that remodeling is progressive and unidirectional, and the third law is that the final goal is (ideally, but not always achievable) a stable, equilibrated scar. This comparison helps to define the boundaries of the system, whether it be the infarct zone, the LV, the heart, or the entire body. This review provides an overview for those not directly in the field and establishes a framework to help prioritize future research directions. PMID- 27376093 TI - Using Na3PO4 to Enhance In vitro Animal Models of Aortic Valve Calcification. AB - BACKGROUND/OBJECTIVES: The pathogenesis of calcific aortic valvular disease (CAVD) involves an active inflammatory process of valvular interstitial cells (VICs) characterized by the activation of specific osteogenic signaling pathways and apoptosis. This process can be studied by analyzing certain molecular markers and gene expression pathways of spontaneous calcification. The purpose of our study is to investigate the role of sodium phosphate (Na3PO4) as a calcification promoter, with the aim of improving in vitro animal models for testing potential calcification inhibitors. MATERIALS AND METHODS: VICs were extracted from 6 healthy 6-month-old fresh porcine hearts by serial collagenase digestion. Quantitative polymerase chain reaction (qPCR) was used to quantify trans differentiation of genes of interest during spontaneous calcification of VICs. Spontaneous calcification of VICs was increased by adding Na3PO4 (3 mM, pH 7.4). The degree of calcification was estimated by Alizarin Red staining for calcium deposition, and Sirius Red staining for collagen. Colorimetric techniques were used to determine calcium and collagen deposition quantitatively. Additionally, the enzymatic activity of alkaline phosphatase (ALP) was measured by a kinetic assay. For statistical analysis we used SPSS and Microsoft Office Excel 2013. RESULTS: Porcine VICs calcify spontaneously with demonstrable calcium and collagen deposition. In this study we observed an increase of calcium and collagen deposition from day 0 to day 14 (calcium: 376%; P<0.001, collagen: 3553%; P<0.001). qPCR analysis of mRNA by day 14 showed the following results: alpha-actin, a marker of myoblast phenotype, was increased to 1.6-fold; P<0.001. Runx2, an osteoblast marker, rose to 1.3 fold; P<0.05, TGF-beta, a promoter of osteogenesis, increased to 3.2-fold; P<0.001, and RhoA, a regulator of nodular formation in myoblasts, increased to 4.5-fold; P<0.001, compared to their levels at day 0. RANKL mRNA and calponin did not change significantly. Treatment of porcine VICs with Na3PO4 (3 mM, pH 7.4) led to a marked increase in calcium deposition by day 14 (522%; P<0.001), and a significant increase in ALP activity by day 7 (228%; P<0.05). There were no significant changes in ALP activity between the groups by day 14. CONCLUSION: This study has demonstrated the upregulation of some specific molecules during spontaneous calcification of aortic VICs with an active increase of calcium, collagen and ALP activity. In this in vitro model it was possible to increase spontaneous VICs calcification with Na3PO4 (3 mM, pH 7.4) to a level in which inhibitors of calcification could be tested to identify a novel potential therapeutic strategy against calcific aortic stenosis. PMID- 27376090 TI - Circulating Biomarkers of Diabetic Retinopathy: An Overview Based on Physiopathology. AB - Diabetic retinopathy (DR) is the main cause of working-age adult-onset blindness. The currently available treatments for DR are applicable only at advanced stages of the disease and are associated with significant adverse effects. In early stages of DR the only therapeutic strategy that physicians can offer is a tight control of the risk factors for DR. Therefore, new pharmacological treatments for these early stages of the disease are required. In order to develop therapeutic strategies for early stages of DR new diagnostic tools are urgently needed. In this regard, circulating biomarkers could be useful to detect early disease, to identify those diabetic patients most prone to progressive worsening who ought to be followed up more often and who could obtain the most benefit from these therapies, and to monitor the effectiveness of new drugs for DR before more advanced DR stages have been reached. Research of biomarkers for DR has been mainly based on the pathogenic mechanism involved in the development of DR (i.e., AGEs, oxidative stress, endothelial dysfunction, inflammation, and proangiogenic factors). This review focuses on circulating biomarkers at both early and advanced stages that could be relevant for the prediction or detection of DR. PMID- 27376094 TI - The (in)dependence of articulation and lexical planning during isolated word production. AB - The number of phonological neighbors to a word (PND) can affect its lexical planning and pronunciation. Similar parallel effects on planning and articulation have been observed for other lexical variables, such as a word's contextual predictability. Such parallelism is frequently taken to indicate that effects on articulation are mediated by effects on the time course of lexical planning. We test this mediation assumption for PND and find it unsupported. In a picture naming experiment, we measure speech onset latencies (planning), word durations, and vowel dispersion (articulation). We find that PND predicts both latencies and durations. Further, latencies predict durations. However, the effects of PND and latency on duration are independent: parallel effects do not imply mediation. We discuss the consequences for accounts of lexical planning, articulation, and the link between them. In particular, our results suggest that ease of planning does not explain effects of PND on articulation. PMID- 27376095 TI - Performance of a Natural Language Processing (NLP) Tool to Extract Pulmonary Function Test (PFT) Reports from Structured and Semistructured Veteran Affairs (VA) Data. AB - INTRODUCTION/OBJECTIVE: Pulmonary function tests (PFTs) are objective estimates of lung function, but are not reliably stored within the Veteran Health Affairs data systems as structured data. The aim of this study was to validate the natural language processing (NLP) tool we developed-which extracts spirometric values and responses to bronchodilator administration-against expert review, and to estimate the number of additional spirometric tests identified beyond the structured data. METHODS: All patients at seven Veteran Affairs Medical Centers with a diagnostic code for asthma Jan 1, 2006-Dec 31, 2012 were included. Evidence of spirometry with a bronchodilator challenge (BDC) was extracted from structured data as well as clinical documents. NLP's performance was compared against a human reference standard using a random sample of 1,001 documents. RESULTS: In the validation set NLP demonstrated a precision of 98.9 percent (95 percent confidence intervals (CI): 93.9 percent, 99.7 percent), recall of 97.8 percent (95 percent CI: 92.2 percent, 99.7 percent), and an F-measure of 98.3 percent for the forced vital capacity pre- and post pairs and precision of 100 percent (95 percent CI: 96.6 percent, 100 percent), recall of 100 percent (95 percent CI: 96.6 percent, 100 percent), and an F-measure of 100 percent for the forced expiratory volume in one second pre- and post pairs for bronchodilator administration. Application of the NLP increased the proportion identified with complete bronchodilator challenge by 25 percent. DISCUSSION/CONCLUSION: This technology can improve identification of PFTs for epidemiologic research. Caution must be taken in assuming that a single domain of clinical data can completely capture the scope of a disease, treatment, or clinical test. PMID- 27376096 TI - Observational Studies of Drug Safety in Multi-Database Studies: Methodological Challenges and Opportunities. AB - INTRODUCTION/OBJECTIVE: The Canadian Network for Observational Drug Effect Studies (CNODES), a network of researchers and databases, is a collaborating center of the Drug Safety and Effectiveness Network. CNODES' main mandate is to conduct observational studies of drug safety based on queries developed and submitted by Health Canada and other federal, provincial, and territorial stakeholders. Through a case study we explore several methodological opportunities and challenges that arise in distributed pharmacoepidemiology networks. CASE STUDY: We use as a case study a study of proton pump inhibitors and hospitalization for community-acquired pneumonia. Challenges arise in the design and conduct of studies at individual sites, and then with processes and methods for combining data. On the other hand, distributed networks provide opportunities, such as the ability to detect and understand heterogeneity, in sample sizes that would typically be impossible for a single study. CONCLUSIONS: Networks such as CNODES provide the opportunity to detect and quantify important safety signals from administrative data, and provide many challenges for methods research in pharmacoepidemiology using distributed data. As networks increase in size and scope of research questions, the need for methodological developments should continue to grow. PMID- 27376097 TI - Appreciating the Nuance of Daily Symptom Variation to Individualize Patient Care. AB - INTRODUCTION: Improving symptoms for patients with chronic illness is difficult due to poor recall and imprecise assessments of therapeutic response to inform treatment decisions. Daily variation in symptoms may obscure subtle improvement or lead to erroneous associations between symptom changes and alteration in medication or dietary regimens. This may lead to mistaken impressions of treatment efficacy (or inefficacy). Mobile health technologies that collect daily patient reported outcome (PRO) data have the potential to improve care by providing more detailed information for clinical decision-making in practice and may facilitate conducting single subject (n-of-1) trials. METHODS: Interrupted time series to prototype mobile health enabled data collection for three patients. We recruited pediatric patients with established inflammatory bowel disease who had persistent symptoms. Based on their self-identified most troubling symptoms, patients were sent customized, daily-automated text messages to assess the extent of their symptoms. Standardized, PRO Measurement Information System (PROMIS) surveys were deployed weekly. Individual statistical process control charts were used to assess variation. Patients met with physicians regularly to interpret their data jointly. RESULTS: We report the experience of 3 patients with inflammatory bowel disease, each with different symptoms. Daily symptom monitoring uncovered important patterns, some of which even patients were unaware before reviewing their symptom data. Important associations were found between symptom variation and changes in medications and diet. PROMIS survey results assessed longitudinally accurately reflected changes in patient symptoms. CONCLUSIONS: We demonstrated how PROs can be implemented in practice. Monitoring and analyzing daily symptom data, using both customized and standard PROs, has the potential to detect meaningful variation in symptom patterns, which can inform clinical decision-making or can facilitate conducting formal n-of-1 trials to further improve outcomes. PMID- 27376098 TI - EBOLA: A PUBLIC HEALTH AND LEGAL PERSPECTIVE. PMID- 27376099 TI - Self-Administration of an Endogenous Cannabinoid 2-Arachidonoylglycerol in Experimentally Naive Rats. PMID- 27376100 TI - (-)-Trans-Delta9-Tetrahydrocannabinol-Like Discriminative-Stimulus Effects of Gabapentin in Cannabis Users. PMID- 27376101 TI - Identification of the Sigma-2 Receptor: Distinct from the Progesterone Receptor Membrane Component 1 (PGRMC1). PMID- 27376102 TI - Time-resolved X-ray spectroscopies of chemical systems: New perspectives. AB - The past 3-5 years have witnessed a dramatic increase in the number of time resolved X-ray spectroscopic studies, mainly driven by novel technical and methodological developments. The latter include (i) the high repetition rate optical pump/X-ray probe studies, which have greatly boosted the signal-to-noise ratio for picosecond (ps) X-ray absorption spectroscopy studies, while enabling ps X-ray emission spectroscopy (XES) at synchrotrons; (ii) the X-ray free electron lasers (XFELs) are a game changer and have allowed the first femtosecond (fs) XES and resonant inelastic X-ray scattering experiments to be carried out; (iii) XFELs are also opening the road to the development of non-linear X-ray methods. In this perspective, I will mainly focus on the most recent technical developments and briefly address some examples of scientific questions that have been addressed thanks to them. I will look at the novel opportunities in the horizon. PMID- 27376103 TI - Ultrafast electron crystallography of the cooperative reaction path in vanadium dioxide. AB - Time-resolved electron diffraction with atomic-scale spatial and temporal resolution was used to unravel the transformation pathway in the photoinduced structural phase transition of vanadium dioxide. Results from bulk crystals and single-crystalline thin-films reveal a common, stepwise mechanism: First, there is a femtosecond V-V bond dilation within 300 fs, second, an intracell adjustment in picoseconds and, third, a nanoscale shear motion within tens of picoseconds. Experiments at different ambient temperatures and pump laser fluences reveal a temperature-dependent excitation threshold required to trigger the transitional reaction path of the atomic motions. PMID- 27376104 TI - Rotational and vibrational dynamics in the excited electronic state of deprotonated and protonated fluorescein studied by time-resolved photofragmentation in an ion trap. AB - Excited state dynamics of deprotonated and protonated fluorescein were investigated by polarization dependent femtosecond time-resolved pump-probe photofragmentation in a 3D ion trap. Transients of deprotonated fluorescein exhibit vibrational wavepacket dynamics with weak polarization dependence. Transients of protonated fluorescein show only effects of molecular alignment and rotational dephasing. The time resolved rotational anisotropy of protonated fluorescein is simulated by the calculated orientational correlation function. The observed differences between deprotonated and protonated fluorescein are ascribed to their different higher lying electronically excited states and corresponding structures. This is partially supported by time-dependent density functional theory calculations of the excited state structures. PMID- 27376105 TI - Is 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Combined With 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23) Superior to PPSV23 Alone for Reducing Incidence or Severity of Pneumonia in Older Adults? A Clin-IQ. AB - Pneumonia infection is a significant cause of morbidity and mortality worldwide. In addition to the public health concerns, pneumonia also accounts for a significant cost to the health care system. Currently there are two leading vaccines targeted against S. pneumoniae: 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13). Until recently the recommendation for adult pneumonia vaccination has been a single dose of PPSV23 for all adults 65 years and older. However, concerns were raised regarding the vaccine's efficacy due to the persistent burden of pneumococcal disease in the elderly population. This paper focuses on two trials which evaluate the safety and efficacy of PCV13 in the adult population. The first study reveals improved immune response with the addition of PCV13 to PPSV23, while the second shows PCV13 was effective in the prevention of vaccine-type community-acquired pneumonia. The two studies observed adequate safety profiles for PCV13 in series with PPSV23 and with PCV13 compared to placebo. PMID- 27376106 TI - Isolation of Mouse Embryo Fibroblasts. AB - Preparation of primary cultures of embryo fibroblasts from genetically engineered mouse strains can provide a valuable resource for analyzing the consequences of genetic alterations at the cellular level. Mouse embryo fibroblasts (MEFs) have been particularly useful in cancer research, as they have facilitated the identification of the genetic changes that allow cells to overcome senescence and proliferate indefinitely in culture. The immortalized MEFs can then acquire additional mutations that lead to anchorage-independent growth and the ability to form tumors in mice. Recently we developed an MEF model system for analysis of the role of the tumor suppressor gene DLC1 in cellular transformation (Qian et al., 2012). In this communication we describe a protocol for the isolation of MEFs from day 13.5-day 14.5 mouse embryos. The MEFs obtained by this procedure are suitable for use in biochemical assays and for further genetic manipulations. PMID- 27376107 TI - Enzymatic Activity Assays in Yeast Cell Extracts. AB - Saccharomyces cerevisiae (S. cerevisiae) (commonly known as baker's yeast) is a model organism that has a similar upstream base excision repair (BER) pathway for the repair of methylated bases as that in mammalian cells, and it is very easy to maintain in the laboratory environment. Here, we described a method to prepare cell extracts from yeast to investigate their enzymatic activities. This protocol is a quick and efficient way to make yeast cell extracts without using commercial kits. PMID- 27376108 TI - Isolation of Splenic Dendritic Cells Using Fluorescence-activated Cell Sorting. AB - The spleen is a vastly vasculated organ and consists of a complex organized network of innate and adaptive immune cells. This permits the specialized functions of the spleen such as antibacterial and antifungal immunity and iron metabolism among others (Mebius and Kraal, 2005). Different dendritic cell (DC) subsets reside in the spleen and can be defined by the expression of unique surface markers. These DC subsets are recognized to perform non-redundant functions in the immune system (Merad et al., 2013). In our recent study, we found that Inositol Requiring Enzyme (IRE)-1 is specifically activated in splenic CD8a+ DCs. Furthermore, loss of X-box binding protein (XBP)-1 - the transcription factor regulated by IRE-1 - resulted in defective cross-presentation of dead cell associated antigens by splenic CD8a+ DCs (Osorio et al., 2014). This protocol allows the isolation of specific DC subsets for experimental use ex-vivo. PMID- 27376109 TI - Quantification of HIV RNA and Human Herpesvirus DNA in Seminal Plasma. AB - Multiple viruses can co-infect the genital tract, modifying the immunologic and virologic milieu and possibly playing a role in viral transmission and pathogenesis. The aim of our studies has been to understand the complex relationships between HIV-1 RNA, and multiple human herpesviruses known to frequently replicate in the genital tract of HIV-infected men (i.e. cytomegalovirus [CMV], Epstein Bar virus [EBV], herpes simplex virus [HSV] types 1 and 2, and human herpesviruses [HHV] 6, 7 and 8) (Gianella et al., 2013a; Gianella et al., 2013b; Gianella et al., 2013c; Gianella et al., 2014). This protocol was designed to collect and process male genital secretion (GS), and to isolate and further quantify HIV RNA and DNA of seven HHV from seminal plasma using quantitative real time PCR technology. PMID- 27376110 TI - Is bone equally responsive to calcium and vitamin D intake from food vs. supplements? Use of (41)calcium tracer kinetic model. AB - BACKGROUND: Few interventions directly compare equivalent calcium and vitamin D from dairy vs. supplements on the same bone outcomes. The radioisotope calcium-41 ((41)Ca) holds promise as a tracer method to directly measure changes in bone resorption with differing dietary interventions. OBJECTIVE: Using (41)Ca tracer methodology, determine if 4 servings/day of dairy foods results in greater (41)Ca retention than an equivalent amount of calcium and vitamin D from supplements. Secondary objective was to evaluate the time course for the change in (41)Ca retention. METHODS: In this crossover trial, postmenopausal women (n = 12) were dosed orally with 100 nCi of (41)Ca and after a 180 day equilibration period received dairy (4 servings/day of milk or yogurt; ~ 1300 mg calcium, 400 IU cholecalciferol (vitamin D3/day)) or supplement treatments (1200 mg calcium carbonate/day and 400 IU vitamin D3/day) in random order. Treatments lasted 6 weeks separated by a 6 week washout (WO). Calcium was extracted from weekly 24 h urine collections; accelerator mass spectrometry (AMS) was used to determine the (41/40)Ca ratio. Primary outcome was change in (41/40)Ca excretion. Secondary outcome was the time course for change in (41)Ca excretion during intervention and WO periods. RESULTS: The (41/40)Ca ratio decreased significantly over time during both treatments; there was no difference between treatments. Both treatments demonstrated a significant retention of (41)Ca within 1-2 weeks (p = 0.0007 and p < 0.001 for dairy and supplements, respectively). WO demonstrated a significant decrease (p = 0.0024) in (41)Ca retention within 1-2 weeks, back to pre-intervention levels. CONCLUSION: These data demonstrate that urinary (41)Ca retention is increased with an increase in calcium and vitamin D intake regardless of the source of calcium, and the increased retention occurs within 1 2 weeks. PMID- 27376111 TI - Editorial. PMID- 27376112 TI - Bacillus Calmette-Guerin (BCG) Treatment Failures in Non-Muscle Invasive Bladder Cancer: What Truly Constitutes Unresponsive Disease. AB - Bacillus Calmette-Guerin (BCG) remains the most effective intravesical therapy for non-muscle invasive bladder cancer but will fail in up to 40% of patients. The ability to identify patients who are least likely to respond to further BCG therapy allows urologists to pursue secondary treatments more likely to convey a recurrence or survival benefit to the patient. We examined the literature to determine what constitutes BCG unresponsive disease. After review, we believe that BCG unresponsive disease should be defined as (1) patients with recurrent high grade T1 disease within 6 months of their primary tumor after at least one course of BCG or patients who have failed at least 2 courses of BCG with either (2) persistent or recurrent pure papillary (Ta) disease within 6 months or (3) persistent or recurrent carcinoma in situ (CIS) within 12 months. PMID- 27376113 TI - The Role of Population-Based Observational Research in Bladder Cancer. AB - While clinical trials have led to many advances in the treatment of bladder cancer, important gaps in knowledge persist. Population-based studies have made important contributions to what is known about bladder cancer and can contribute unique insights to practice and policy. In addition to evaluating effectiveness of interventions in routine practice, population-based studies can identify gaps between evidence and practice, and generate knowledge that cannot be gained from clinical trials. In this review we will highlight how population-based research has informed practice, policy, and the research agenda for bladder cancer. PMID- 27376114 TI - Novel Simulation Model of Non-Muscle Invasive Bladder Cancer: A Platform for a Virtual Randomized Trial of Conservative Therapy vs. Cystectomy in BCG Refractory Patients. AB - Introduction: There have been no randomized controlled trials (RCTs) evaluating the clinical or economic benefit of mitomycin C intravesical therapy vs. radical cystectomy in patients with high-risk non-muscle invasive bladder cancer (NMIBC). We used the Archimedes computational model to simulate RCT comparing radical cystectomy versus intravesical mitomycin C (MMC) therapy to evaluate the clinical and economic outcomes for BCG-refractory NMIBC as well demonstrate the utility of computer based models to simulate a clinical trial. Methods: The Archimedes model was developed to generate a virtual population using the Surveillance Epidemiology and End Results database, other clinical trials, and expert opinions. Patients selected were diagnosed with NMIBC (=T2a) or BCG-refractory stage Tis-T1 urothelial bladder cancer. Patients were excluded if prior RT exposure was used as treatment for bladder cancer or if cause of death was due to post-operative complications. A digit matching propensity score algorithm was used to match patients with prior radiation treatment to those without prior treatment. Cox regression analysis for time until death was performed following creation of the propensity score matched sample. Results: 29 patients with history of RT were matched with two controls each, resulting in a dataset of 87 observations in the event model. Results from the Cox model indicate a significantly increased hazard ratio for death at 2.22 (p = 0.047, 95% CI: 1.015-4.860) given a history of prior radiation therapy. Conclusions: In a small cohort, bladder cancer patients who underwent cystectomy had a significantly higher risk of death in the face of prior pelvic RT. This effect was found to be independent of surgical complications, numerous established patient characteristics and comorbidities traditionally predictive of survival. PMID- 27376121 TI - Inhibiting Immune Checkpoints for the Treatment of Bladder Cancer. AB - BACKGROUND: Increasing evidence supporting the role of immune checkpoint blockade in cancer management has been bolstered by recent reports demonstrating significant and durable clinical responses across multiple tumour types, including metastatic urothelial carcinoma (mUC). The majority of these results are achieved via blockade of the programmed death (PD) axis, which like CTLA-4 blockade permits T-cell activation and immune-mediated anti-tumour activity- essentially harnessing the patient's own immune system to mount an anti neoplastic response. However, while clinical responses can be striking, our understanding of the biology of immune checkpoint blockade is only beginning to shed light on how to maximize and even improve patient outcomes with immune checkpoint blockade, especially in UC. METHODS: We performed a literature review for immune checkpoint blockade with a focus on rationale for checkpoint therapy and outcomes in UC. We also highlight the advances made in other tumour types, with a focus on the recent 2015 meeting of the American Society for Clinical Oncology. RESULTS: In heavily pre-treated UC, trials are suggesting objective response rates above 30% . These impressive results are seen across multiple different tumour types, especially those with high burden of DNA level mutations. Identification of prognostic biomarkers is currently under investigation, in order to improve patient selection. Interestingly, response to PD-1 directed therapy is seen even in patients with no evidence of PD-1 positivity on immunohistochemistry. This has led to the development of enhanced biomarkers including assessing DNA mutation rates and immune gene signatures, to improve patient selection. CONCLUSIONS: Immune checkpoint blockade is an exciting cancer treatment modality which is demonstrating impressive clinical results across multiple tumour types. For UC, anti-PD directed therapy represents a much needed treatment in the metastatic, post chemotherapy context. Potential for these agents to have clinical utility in non-metastatic UC is still to be assessed. PMID- 27376120 TI - Management of T1 Urothelial Carcinoma of the Bladder: What Do We Know and What Do We Need To Know? AB - T1 bladder cancer constitutes approximately 25% of incident bladder cancers, and as such carries an important public health impact. Notably, it has a heterogeneous natural history, with large variation in reported oncologic outcomes. Optimal risk-stratification is essential to individualize patient management, targeting those at greatest risk of progression for aggressive therapies such as early cystectomy, while allowing others to safely pursue bladder-preserving approaches including intravesical bacillus Calmette-Guerrin (BCG). Current strategies for diagnosis, risk-stratification, and treatment are imperfect, but emerging technologies and molecular approaches represent exciting opportunities to advance clinical paradigms in management of this disease entity. PMID- 27376122 TI - Comparison of Guidelines on Non-Muscle Invasive Bladder Cancer (EAU, CUA, AUA, NCCN, NICE). AB - BACKGROUND: Non-muscle invasive bladder cancer (NMIBC) represents a considerably diverse patient group and the management of this complex disease is debatable. A number of panels from Europe and North America have convened on the topic and recently released guideline documents. OBJECTIVE: The purpose was to compare and contrast the NMIBC guideline recommendations from the EAU (Europe), CUA (Canada), NCCN (United States), AUA (United States), and NICE (United Kingdom). METHODS: All unabridged guideline documents were reviewed by the authors and comparisons were completed according to major topics in NMIBC. RESULTS: Despite a paucity of high level evidence regarding the majority of management topics in NMIBC, there was general agreement among the various guideline panels. Differences mainly centered on the categories of evidence synthesized and grades of recommendations. Each document offers a unique presentation of the available literature and guideline recommendation. CONCLUSIONS: The guidelines for NMIBC from the EAU, CUA, AUA, NCCN, and NICE provide considerable consensus regarding the management of this often difficult disease. Clinicians are encouraged to familiarize themselves with all of the guidelines in order to determine which style of presentation would be most useful to their current practice. PMID- 27376123 TI - Bladder Cancer Molecular Taxonomy: Summary from a Consensus Meeting. AB - The advent of Omics technologies has been key to the molecular subclassification of urothelial bladder cancer. Several groups have used different strategies to this aim, with partially overlapping findings. The meeting at the Spanish National Cancer Research Center-CNIO was held to discuss such classifications and reach consensus where appropriate. After updated presentations on the work performed by the teams attending the meeting, a consensus was reached regarding the existence of a group of Basal-Squamous-like tumors - designated BASQ - charaterized the high expression of KRT5/6 and KRT14 and low/undetectable expression of FOXA1 and GATA3. An additional tumor subgroup with urothelial differentiation features was recognized whose optimal molecular definition is required. For other subtypes described, more work is needed to determine how robust they are and how to best define them at the molecular level. PMID- 27376124 TI - Limited Funds for Bladder Cancer Research and What Can We Do About It. AB - Bladder cancer is frequent, has a high mortality, is expensive and treatment options have not improved over a long time. One of the most important reasons for the relative lack of improvement in treatment of bladder cancer is the low funding for research on bladder cancer. A second reason is that incidence figures in some countries are too low because non-muscle invasive tumors are not registered. We suggest that the bladder cancer community advocates research on bladder cancer and informs policy makers on the underfunding situation. In addition, we need to convince the statisticians that registration should encompass all bladder tumors. PMID- 27376125 TI - Pelvic Lymph Node Dissection may be Limited on the Contralateral Side in Strictly Unilateral Bladder Cancer without Compromising Oncological Radicality. AB - BACKGROUND: Results of a dynamic multimodality mapping study showed no lymphatic drainage of the lateral bladder wall to the contralateral internal iliac region. OBJECTIVES: To validate whether pathoanatomical mapping in bladder cancer (BC) patients can confirm these results. METHODS: Between 01/2000 and 07/2013, 825 BC patients preoperatively staged >=pT1 and without clinical signs of metastases (cN0 cM0) underwent extended pelvic lymph node dissection (ePLND) and radical cystectomy at our department. Of these patients, 23% (193/825) were lymph node (LN) positive in the pathological specimen; 26% (51/193) of this subgroup had strictly unilateral BC. Pathoanatomical mapping was used to retrospectively validate the distribution of LN involvement in these 51 patients. RESULTS: A median of 35 LNs were removed per patient (range: 13-80 LNs), with a median of 2 positive LNs (range: 1-14 LNs). 27% (14/51) of patients presented with LN metastases on the contralateral side. No positive LNs were found in the contralateral internal iliac region or the contralateral fossa of Marcille. 10% (5/51) of patients had LN metastases only on the contralateral side without evidence of metastases on the tumor-bearing side. CONCLUSIONS: Our findings corroborate the data of a dynamic mapping study showing bilateral lymphatic drainage in almost one third of patients with strictly unilateral BC, but no lymphatic drainage from the lateral bladder wall to the contralateral internal iliac region. If prospective studies confirm these results, the contralateral internal iliac region may be omitted during ePLND in patients with strictly unilateral BC. PMID- 27376126 TI - Editorial concerning "Pelvic lymph node dissection may be limited on the contralateral side in strictly unilateral bladder cancer without compromising oncological radicality". PMID- 27376127 TI - Reply from Authors to the Editorial Comment. PMID- 27376128 TI - BcCluster: A Bladder Cancer Database at the Molecular Level. AB - BACKGROUND: Bladder Cancer (BC) has two clearly distinct phenotypes. Non-muscle invasive BC has good prognosis and is treated with tumor resection and intravesical therapy whereas muscle invasive BC has poor prognosis and requires usually systemic cisplatin based chemotherapy either prior to or after radical cystectomy. Neoadjuvant chemotherapy is not often used for patients undergoing cystectomy. High-throughput analytical omics techniques are now available that allow the identification of individual molecular signatures to characterize the invasive phenotype. However, a large amount of data produced by omics experiments is not easily accessible since it is often scattered over many publications or stored in supplementary files. OBJECTIVE: To develop a novel open-source database, BcCluster (http://www.bccluster.org/), dedicated to the comprehensive molecular characterization of muscle invasive bladder carcinoma. MATERIALS: A database was created containing all reported molecular features significant in invasive BC. The query interface was developed in Ruby programming language (version 1.9.3) using the web-framework Rails (version 4.1.5) (http://rubyonrails.org/). RESULTS: BcCluster contains the data from 112 published references, providing 1,559 statistically significant features relative to BC invasion. The database also holds 435 protein-protein interaction data and 92 molecular pathways significant in BC invasion. The database can be used to retrieve binding partners and pathways for any protein of interest. We illustrate this possibility using survivin, a known BC biomarker. CONCLUSIONS: BcCluster is an online database for retrieving molecular signatures relative to BC invasion. This application offers a comprehensive view of BC invasiveness at the molecular level and allows formulation of research hypotheses relevant to this phenotype. PMID- 27376129 TI - Independent Replication of Published Germline Polymorphisms Associated with Urinary Bladder Cancer Prognosis and Treatment Response. AB - BACKGROUND: Many studies investigated the prognostic or predictive relevance of single nucleotide polymorphisms (SNPs) in biologically plausible genes in urinary bladder cancer (UBC) patients. Most published SNP associations have never been replicated in independent patient series. OBJECTIVE: To independently replicate all previously reported associations between germline SNPs and disease prognosis or treatment response in UBC. METHODS: A Pubmed search was performed to identify studies published by July 1, 2014 reporting on germline SNP associations with UBC prognosis or treatment response. For the replication series, consisting of 1,284 non-muscle-invasive bladder cancer (NMIBC) and 275 muscle-invasive or metastatic bladder cancer (MIBC) patients recruited through the Netherlands Cancer Registry, detailed clinical data were retrieved from medical charts. Patients were genotyped using a genome-wide SNP array. SNP association with recurrence-free, progression-free, and overall survival (OS) within specific patient and treatment strata was tested using Cox regression analyses. RESULTS: For only six of the 114 evaluated SNPs, the association with either UBC prognosis or treatment response was replicated at the p < 0.05 level: rs1799793 (ERCC2) and rs187238 (IL18) for BCG recurrence; rs6678136 (RGS4) and rs11585883 (RGS5) for NMIBC progression; rs12035879 (RGS5) and rs2075786 (TERT) for MIBC OS. CONCLUSIONS: Non-replicated genetic associations in the literature require cautious interpretation. This single replication does not provide definitive proof of association for the six SNPs, and non-replication of other SNPs may result from population-specific effects or the retrospective patient enrollment. PMID- 27376130 TI - Concordance in Biomarker Status Between Bladder Tumors at Time of Transurethral Resection and Subsequent Radical Cystectomy: Results of a 5-year Prospective Study. AB - PURPOSE: To assess the concordance rate in alterations of molecular markers at the time of transurethral resection (TUR) and subsequent radical cystectomy (RC) among patients with high-grade urothelial carcinoma of the bladder (UCB). METHODS: We prospectively performed immunohistochemical staining p53, p21, p27, Ki-67 and cyclin E1 on TUR and on RC specimens from 102 patients treated with RC and bilateral lymphadenectomy for high-grade UCB. We analyzed the concordance rate of individual markers and of the number of altered markers. Concordant and discordant findings were reported in the overall population and according to clinical stage. RESULTS: Median patient age was 74 years (IQR 67-79) and mostly male (86%). Median time from TUR to RC was 1.5 months (IQR 1.0-2.4). Clinical stage at time of RC was cTa/Tis/T1 in 50% , cT2 in 47% , and cT4 in 1% of patients Nine (9%) patients received neoadjuvant chemotherapy. The concordance of biomarkers between TUR and RC specimens was 92.2% , 77.5% , 80.4% , 77.5% , and 83.3% for cyclin E1, p21, p27, p53 and Ki-67, respectively. The concordance between number of altered biomarkers was 51.0%. CONCLUSIONS: The rate of individual marker alterations at time of TUR closely approximates that found at RC specimens. However, the correlation of number of altered markers is lower. Molecular marker status at TUR could help predict the marker status at RC and may help guide multimodal therapeutic planning. PMID- 27376131 TI - Hypoxia Marker GLUT-1 (Glucose Transporter 1) is an Independent Prognostic Factor for Survival in Bladder Cancer Patients Treated with Radical Cystectomy. AB - BACKGROUND: Tumour hypoxia, which is frequent in many cancer types, is associated with treatment resistance and poor prognosis. The role of hypoxia in surgically treated bladder cancer (BC) is not well described. We studied the role of hypoxia in two independent series of urothelial bladder cancers treated with radical cystectomy. METHODS: 279 patients from the University Hospital Network (UHN), Toronto, Canada, and Turku University, Finland were studied. Hypoxia biomarkers (HIF1-alpha, CAIX, GLUT-1) and proliferation marker Ki-67 were analyzed with immunohistochemistry using defined tissue microarrays. Kaplan-Meier methods and Cox proportional hazards regression models were used to investigate prognostic role of the factors. RESULTS: In univariate analyses, strong GLUT-1 positivity and a high Ki-67 index were associated with poor survival. In multivariate model containing clinical prognostic variables, GLUT-1 was an independent prognostic factor associated with worse disease-specific survival (HR 2.9, 95% CI 0.7-12.6, Wald p = 0.15 in the Toronto cohort and HR 3.2, 95% CI 1.3-7.5, Wald p = 0.0085 in the Turku cohort). CONCLUSION: GLUT-1 is frequently upregulated and is an independent prognostic factor in surgically treated bladder cancer. Further studies are needed to evaluate the potential role of hypoxia-based and targeted therapies in hypoxic bladder tumours. PMID- 27376132 TI - Phase I Study of Everolimus in Combination with Gemcitabine and Split-Dose Cisplatin in Advanced Urothelial Carcinoma. AB - BACKGROUND: Cisplatin-based combination chemotherapy is standard first-line treatment for patients with advanced urothelial carcinoma (UC). Molecular profiling studies reveal that the PI3K/AKT/mTOR pathway is altered in a significant percentage of UCs. OBJECTIVE: We conducted a phase I trial to evaluate the feasibility of combining the mTOR inhibitor everolimus with gemcitabine and split-dose cisplatin (GC) in advanced UC in the first-line setting. METHODS: Patients received gemcitabine 800 mg/m2 and cisplatin 35 mg/m2 on days 1 and 8 of 21-day cycles for a total of 6 cycles in combination with everolimus at increasing dose levels (DL1:5 mg QOD, DL2:5 mg daily, DL3:10 mg daily) following a standard 3+3 design. Responses were assessed every 2 cycles. Patients with at least stable disease (SD) continued everolimus until progression. Goals were to establish dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) for the combination. RESULTS: 12 patients were enrolled, 3 at DL1, 3 at DL2, and an additional 6 at DL1 *(DL1 following de-escalation). 3/3 patients at DL2 had DLTs during cycle 1. 2/8 evaluable patients at DL1/DL1 * had DLTs during cycle 1. DLTs were primarily hematologic. Further toxicities, also primarily hematologic, were observed during later treatment cycles, leading to 8 chemotherapy dose reductions overall. Partial responses were observed in 4/10 evaluable patients, and SD in 5/10. Median overall survival was 10.8 months (95% CI 6.9, not reached). CONCLUSIONS: The maximum tolerated dose was reached at the lowest dose level, 5 mg QOD, for everolimus in combination with gemcitabine and split-dose cisplatin in advanced UC. The regimen was limited by hematologic toxicity. PMID- 27376133 TI - Clinical Trials Corner. PMID- 27376135 TI - Effects of Androgen and Estrogen Receptor Signaling Pathways on Bladder Cancer Initiation and Progression. AB - Epidemiologic studies have long demonstrated clear differences in incidence and progression of bladder cancer between genders suggesting that the mechanisms of development and progression in these tumors have a strong association with steroid hormonal pathways. Such observations led to preclinical studies investigating the role of androgen and estrogen receptors, as well as their cognate hormones in bladder cancer initiation and progression. Using various in vitro cell line assays and in vivo mouse models, studies have elucidated different mechanisms and signaling pathways through which these steroid receptors may participate in this disease. More recently, RNA expression data from multiple studies revealed a luminal subtype of bladder cancer that exhibited an estrogen receptor signaling pathway, making it a strong candidate for further consideration of targeted therapies in the future. Despite the promising preclinical data demonstrating potential roles for both antiandrogen and antiestrogen strategies targeting these pathways in different stages of bladder cancer, only two clinical trials are currently active and accruing patients for such clinical studies. Targeted therapies in bladder cancer are a large unmet need and have the potential to change treatment paradigms and improve oncological outcomes of patients with bladder cancer. PMID- 27376136 TI - Pursuing Quality in the Application of Bladder Cancer Quality of Life Research. AB - Patient-reported outcomes (PRO), including health-related quality of life (HRQOL) measures, represent important means for evaluating patients' health outcomes and for guiding health care decisions made by patients, practitioners, investigators, and policy makers. In spite of the large number of studies examining HRQOL in patients with bladder cancer, very few review articles investigated this topic. Because these review studies report mixed results, incorporating bladder cancer HRQOL measures into standard urological practice is not a viable option. In this non-systematic review of the literature and commentary we note some general concerns regarding PRO research, but our primary focus is on the HRQOL methodology within the context of two types of bladder cancer: muscle invasive and non-muscle invasive bladder cancer. Considering bladder cancer HRQOL as the interaction of four areas of the assessment process (i.e., what model of HRQOL to choose, what instruments are available to fit the choice, how interpretation of the resulting data fits the model, and how to derive some utility from the chosen model) and the two types of disease (i.e., muscle invasive and non-muscle invasive) may move us toward a better understanding of bladder cancer HRQOL. Establishing a useful model of perceived general health or specific symptoms is the first and most important step in developing the responsive bladder cancer HRQOL measures necessitated by clinical settings. PMID- 27376137 TI - Bladder Preservation for Muscle Invasive Bladder Cancer. AB - The standard treatment for muscle invasive bladder cancer (MIBC) has been considered to be radical cystectomy (RC) with pelvic lymphadenectomy. However morbidity and impact on quality of life is significant. Radiotherapy has been used in MIBC patients who choose bladder preservation or who are unfit for RC with comparable outcomes. Evidence from some prospective and large retrospective series supports the use of radiotherapy as an attractive alternative option. In this paper we review the evidence and practice of bladder preservation strategies with radiotherapy for muscle invasive bladder cancer. PMID- 27376139 TI - Collaborating to Move Research Forward: Proceedings of the 10th Annual Bladder Cancer Think Tank. AB - The 10th Annual Bladder Cancer Think Tank was hosted by the Bladder Cancer Advocacy Network and brought together a multidisciplinary group of clinicians, researchers, representatives and Industry to advance bladder cancer research efforts. Think Tank expert panels, group discussions, and networking opportunities helped generate ideas and strengthen collaborations between researchers and physicians across disciplines and between institutions. Interactive panel discussions addressed a variety of timely issues: 1) data sharing, privacy and social media; 2) improving patient navigation through therapy; 3) promising developments in immunotherapy; 4) and moving bladder cancer research from bench to bedside. Lastly, early career researchers presented their bladder cancer studies and had opportunities to network with leading experts. PMID- 27376138 TI - Summary and Recommendations from the National Cancer Institute's Clinical Trials Planning Meeting on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer. AB - The NCI Bladder Cancer Task Force convened a Clinical Trials Planning Meeting (CTPM) Workshop focused on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer (NMIBC). Meeting attendees included a broad and multi-disciplinary group of clinical and research stakeholders and included leaders from NCI, FDA, National Clinical Trials Network (NCTN), advocacy and the pharmaceutical and biotech industry. The meeting goals and objectives were to: 1) create a collaborative environment in which the greater bladder research community can pursue future optimally designed novel clinical trials focused on the theme of molecular targeted and immune-based therapies in NMIBC; 2) frame the clinical and translational questions that are of highest priority; and 3) develop two clinical trial designs focusing on immunotherapy and molecular targeted therapy. Despite successful development and implementation of large Phase II and Phase III trials in bladder and upper urinary tract cancers, there are no active and accruing trials in the NMIBC space within the NCTN. Disappointingly, there has been only one new FDA approved drug (Valrubicin) in any bladder cancer disease state since 1998. Although genomic-based data for bladder cancer are increasingly available, translating these discoveries into practice changing treatment is still to come. Recently, major efforts in defining the genomic characteristics of NMIBC have been achieved. Aligned with these data is the growing number of targeted therapy agents approved and/or in development in other organ site cancers and the multiple similarities of bladder cancer with molecular subtypes in these other cancers. Additionally, although bladder cancer is one of the more immunogenic tumors, some tumors have the ability to attenuate or eliminate host immune responses. Two trial concepts emerged from the meeting including a window of opportunity trial (Phase 0) testing an FGFR3 inhibitor and a second multi-arm multi-stage trial testing combinations of BCG or radiotherapy and immunomodulatory agents in patients who recur after induction BCG (BCG failure). PMID- 27376140 TI - Bacillus Calmette-Guerin (BCG) Treatment Failures with Non-Muscle Invasive Bladder Cancer: A Data-Driven Definition for BCG Unresponsive Disease. AB - Objective: To create the first data-driven definition for those unlikely to benefit from further BCG treatment. Materials and Methods: The database created for the Phase 2 BCG-Interferon-alpha 2B (IFN) study was queried and BCG failure patients were identified (n = 334). Full study protocols have previously been published. Separate models were constructed for analysis of patients with any CIS (pure or concomitant) and pure papillary disease. Variables considered included age, gender, stage, grade, tumor size and focality (for papillary only), number of prior BCG courses, and prior BCG failure interval. Results: Patients with recurrent CIS within 6 months of their most recent prior BCG course (HR 2.56, p < 0.01) and >=2 prior BCG failures (HR 1.54, p < 0.01) responded worst to repeat intravesical therapy. Those with CIS recurrence at 6-12 months did not differ from those recurring within 6 months (HR = 0.88, p = 0.71). Patients with recurrent papillary disease within 6 months (HR 1.82, p = 0.02), >=2 BCG failures (HR 1.54, p = 0.03), and multifocal disease (HR 2.05, p < 0.01) responded worst to therapy. Patients with T1 disease remained disease free in 38% of cases (24 51% 95% CI) at 2 years with low rates of progression. Conclusions: Patients who fail two courses of BCG with either persistent or recurrent multifocal papillary disease within 6 months or CIS within 12 months of their prior BCG should be considered BCG unresponsive. Recurrent T1 disease respond reasonably well to another course with low progression rates but further investigation is warranted. PMID- 27376141 TI - Do African American Patients Treated with Radical Cystectomy for Bladder Cancer have Worse Overall Survival? Accounting for Pathologic Staging and Patient Demographics Beyond Race Makes a Difference. AB - Background: It is estimated that 74,000 men and women in the United States will be diagnosed with bladder cancer and 16,000 will die from the disease in 2015. The incidence of bladder cancer in Caucasian males is double that of African American males, but African American men and women have worse survival. Although factors contributing to this disparity have been analyzed, there is still great uncertainty as to why this disparity exists. Objective: To evaluate whether the disparities in bladder cancer survival after radical cystectomy for transitional cell carcinoma (TCC) of the bladder amongst African American (AA) and Caucasian patients is attributable to patient demographics, year of diagnosis, and/or tumor characteristics. Methods: Using Surveillance, Epidemiology, and End Results Program (SEER) data from 1973-2011, African American and Caucasian patients treated with a radical cystectomy for TCC of the bladder were identified. Primary outcomes were all-cause and cancer-specific mortality. Differences in survival between African Americans and Caucasian patients were assessed using chi-square tests for categorical variables and Student's t-tests for continuous variables. Cox proportional hazards regression was used to measure the hazard ratio for African Americans compared to Caucasians for all-cause and cancer-specific mortality. In addition, coarsened matching techniques within narrow ranges, were used to match African American and Caucasian patients on the basis of age, sex, and cancer stage. Following matching, differences in all-cause and cancer specific mortality were again assessed using a stratified Cox proportional hazards model, using the matching strata for the regression strata. Results: The study cohort consisted of 21,406 African American and Caucasian patients treated with radical cystectomy for bladder urothelial cancer, with 6.2% being African American and 73.9% male. African American patients had worse all-cause and cancer specific mortality in the univariable analysis (all-cause: HR: 1.23; 95% CI 1.15 1.32, p < 0.001); bladder-cancer specific: HR 1.21; 95% CI 1.11-1.33; p < 0.001). However, after accounting for sex, age, year of diagnosis, marital status, region of treatment, and stage at cystectomy, all-cause mortality was significant (HR 1.20; 95% CI 1.12-1.29; p < 0.0001), but not bladder-cancer specific mortality (HR 1.09; 95% CI 1.00-1.20; p < 0.053). Predictors of bladder cancer specific mortality were age, sex, stage of disease, and marital status. The matched analysis yielded a roughly 1 : 15 match, with 22,511 Caucasians being matched to 1,509 African American patients. In the matched analysis, African Americans had increased all-cause mortality (HR 1.17; 95% CI 1.09-1.26; p < 0.0001), but bladder-cancer specific mortality was no longer significant (HR 1.08; 95% CI 0.99-1.18; p < 0.102). Conclusions: African Americans who undergo a cystectomy are more likely to die, but not necessarily solely because of bladder cancer. Although African American patients have worse all-cause and cancer specific mortality in univariable models, after controlling for sex, age, year of diagnosis, marital status, region of treatment, and stage at cystectomy, African American patients still have worse overall survival, but equivalent bladder cancer specific survival. Differences in age, sex, and stage at diagnosis explain some, but not all of the differences in survival. PMID- 27376142 TI - Using Analytic Morphomics to Understand Short-Term Convalescence after Radical Cystectomy. AB - Background: Data from the general surgery literature suggests that patient morphometric data obtained from preoperative imaging may help predict a patient's risk around surgery. Objectives: In this context, we evaluated for associations between psoas muscle area and short-term convalescence following radical cystectomy. Methods: After identifying patients who underwent radical cystectomy at our institution (2008 to 2013), we calculated their psoas muscle area from staging computed tomography scans using established analytic morphomic techniques. We then determined early recovery among patients with high and low psoas muscle area using the validated Convalescence and Recovery Evaluation (CARE) questionnaire-a 27-item survey, divided into four domains (activity, cognitive, gastrointestinal, and pain recovery). Finally, we assessed the relationship between psoas muscle area and changes in CARE scores with nested linear regression models. Results: Among the 86 men and among 31 women in our cohort, the median total psoas muscle area was 2,544 mm2 and 1,511 mm2, respectively (P < 0.001 for the comparison). While there was no association between psoas muscle area and recovery in men, women with higher (versus lower) total psoas muscle area had smaller decreases in their pain scores postoperatively and a quicker return to their baseline level (P = 0.05). Activity scores also approached baseline levels faster among women with higher psoas muscle area, although this finding did not reach statistical significance. Conclusions: Psoas muscle area is potentially an important preoperative predictor of recovery for women undergoingradical cystectomy. More broadly speaking, analytic morphomics may represent a novel approach to better understand perioperative risk. PMID- 27376143 TI - A Nonselective Cyclooxygenase Inhibitor Enhances the Activity of Vinblastine in a Naturally-Occurring Canine Model of Invasive Urothelial Carcinoma. AB - Background: Chemotherapy is expected to remain an important part of invasive urothelial carcinoma (UC) treatment. Strategies to enhance chemotherapy efficacy are needed. Objective: To determine the chemotherapy-enhancing effects of a nonselective cyclooxygenase (COX) inhibitor on vinblastine in a naturally occurring canine model of invasive UC. Methods: With IACUC approval, privately owned dogs with naturally-occurring histologically-diagnosed invasive UC, expected survival >=6 weeks, and informed owner consent were randomly allocated to receive vinblastine (2.5 mg/m2 intravenously every 2 weeks) plus piroxicam (0.3 mg/kg daily per os) or vinblastine alone (same dose) with the option to receive piroxicam alone when vinblastine failed. Scheduled evaluations included physical exam, standard laboratory analyses, thoracic radiography, abdominal ultrasonography, and standardized measurement of urinary tract tumors. Results: Dogs receiving vinblastine alone (n = 27) and vinblastine-piroxicam (n = 24) were similar in age, sex, breed, tumor stage, and grade. Remission occurred more frequently (P < 0.02) with vinblastine-piroxicam (58.3%) than with vinblastine alone (22.2%). The median progression free interval was 143 days with vinblastine alone and 199 days with the combination. Interestingly, the overall median survival time was significantly longer (P < 0.03) in dogs receiving vinblastine alone followed by piroxicam alone (n = 20, 531 days) than in dogs receiving the combination (299 days). Treatment was well tolerated in both arms. Conclusions: Piroxicam significantly enhanced the activity of vinblastine in dogs with UC where the cancer closely mimics the human condition, clearly justifying further study. The study suggest the potential importance of tracking COX inhibitor use in patients in clinical trials as COX inhibitors could affect treatment response. PMID- 27376144 TI - A Multi-Center International Study Assessing the Impact of Differences in Baseline Characteristics and Perioperative Care Following Radical Cystectomy. AB - Background: To identify potential avenues for quality improvement, we compared the variations in clinical practice and their association with perioperative morbidity and mortality following radical cystectomy (RC) for bladder cancer in the United States (US) and Japan. Methods: We reviewed our retrospectively collected database of 2240 patients who underwent RC for bladder cancer at the University of Michigan (n = 1427) and in 21 Japanese institutions (n = 813) between 1997 and 2014. We performed a systematic comparison of clinical and perioperative factors and assessed predictors of perioperative morbidity and mortality. Death within 90 days of surgery was the primary outcome. Results: There were apparent differences between the two study populations. Notably, US patients had a significantly greater BMI and higher ASA score. In Japanese institutions, median postoperative hospital stay was significantly higher (40 days vs. 7 days, p < 0.001) and 90-day readmission rates were significantly lower (0.6% vs. 26.8% , p < 0.001). There was a total of 1372/2240 (61.2%) patients with complications within 90 days and 66/2240 (2.9%) patient deaths. Significant predictors of 90-day mortality were older age (OR 1.04, CI 1.01 1.07), higher body mass index (OR 1.07, CI 1.02-1.12), node-positive disease (OR 3.14, CI 1.78-5.47), increased blood loss (OR 1.02, CI 1.01-1.03), and major (Clavien-grade 3 or greater) complication (OR 3.29, CI 1.88-5.71). Conclusion: Despite major differences in baseline characteristics and care of cystectomy patients between the two study populations, peri-operative mortality rates proved to be comparable. This data supports an exploration of non-traditional factors that may influence mortality after cystectomy. PMID- 27376147 TI - Clinical Trials Corner. PMID- 27376145 TI - Benefit of Adjuvant Chemotherapy and Pelvic Lymph Node Dissection in pT3 and Node Positive Bladder Cancer Patients Treated with Radical Cystectomy. AB - Background: Benefits of adjuvant chemotherapy (AC) and extent of pelvic lymph node dissection (PLND) in radical cystectomy (RC) are debated. Results from randomized trials are still expected. Objective: To analyze the effects of AC and PLND in two academic centers with opposite policies regarding their use. Methods: 581 bladder cancer patients who underwent RC without neoadjuvant chemotherapy, from Toronto (University Health Network), Canada, and Turku University Hospital, Finland were included. Disease specific survival (DSS) and failure patterns were assessed. Results: Centers differed in PLND rate (93% and 36% in Toronto and Turku respectively, p < 0.001), PLND extent (>=10 removed nodes, 58% vs. 8%, p < 0.001) and AC rate (21% vs. 2%, p < 0.001). Survival between centers among pT<=1 or pT4 patients was similar. pT3 patients in Toronto had an improved 10 year DSS (43% vs. 22%, p = 0.025). Distant failures were less common after AC (HR 0.56, 95% CI 0.33-0.98, p < 0.042). In node positive (N+) patients, mortality was significantly higher in Turku (HR 2.19, 95% CI 1.44-3.34, p < 0.001) and lower in patients receiving AC (HR 0.60, 95% CI 0.37-0.99, p = 0.044). 41% DSS at 10 years was observed in N+ Toronto patients. Limitations included the non randomized retrospective design and absence of propensity score analysis. Conclusion: Combining AC and PLND to RC is associated with improved survival in pT3 and N+ patients. PLND did not affect survival independently but helps in selecting patients for AC. Our data adds to the growing body of evidence supporting the usefulness of AC in addition to PLND in high risk patients operated by cystectomy. PMID- 27376146 TI - The Impact of Blue Light Cystoscopy with Hexaminolevulinate (HAL) on Progression of Bladder Cancer - A New Analysis. AB - Background: The International Bladder Cancer Group (IBCG) recently proposed a new definition of disease progression in non-muscle invasive bladder cancer (NMIBC), including change in T-stage, change to T2 or higher or change from low to high grade. Objective: To establish whether blue light cystoscopy with hexaminolevulinate (HAL) impacts the rate of progression and time to progression using the revised definition. Methods: An earlier long-term follow-up of a controlled Phase III study reported outcomes following blue light cystoscopy with HAL (255 patients) or white light (WL) cystoscopy (261 patients) in NMIBC patients. The data was re-analysed according to the new definition. Results: In the original analysis, after 4.5 years (median), eight HAL and 16 WL patients were deemed to have progressed (transition from NMIBC to muscle invasive bladder cancer, (T2-4)). According to the new definition, additional patients in both groups were found to have progressed: 31 (12.2%) HAL vs 46 (17.6%) WL (p = 0.085) with four (1.6%) HAL and 11 (4.2%) WL patients progressing from Ta to CIS. Time to progression was longer in the HAL group (p = 0.05). Conclusions: Applying the new IBCG definition there was a trend towards a lower rate of progression in HAL patients, particularly in those progressing from Ta to CIS. Time to progression was significantly prolonged. This suggests that patients should receive blue light cystoscopy with HAL rather than WL at resection. Adoption of the new definition could allow more patients at risk of progression to be treated appropriately earlier. PMID- 27376149 TI - The Process of Separating Bovine Serum Albumin Using Hydroxyapatite and Active Babassu Coal (Orbignya martiana). AB - Bovine serum albumin is one of the major serum proteins; it plays an important role as a result of its functional and nutritional properties which have bioactive peptides. Adsorption method was used to separate protein, which involves hydroxyapatite, synthetic hydroxyapatite, and active babassu coal. Initially, characterization was carried out using the zeta potential of the adsorbents. Kinetic pseudo-first- and pseudo-second-order models were applied. For isotherms, equilibrium data studies were carried out using the Langmuir and Freundlich models, in addition to determining the efficiency of adsorptive process. The results of the zeta potential showed loads ranging from +6.9 to 42.8 mV. The kinetic data were better represented in the pseudo-second-order model with chemisorption characteristics. The adsorption capacity of the adsorbents decreased as pH increased, indicating that the electrostatic bonds and some functional groups of active babassu coal contributed to the reduction of adsorption, especially oxygen linked to carbon atoms. The value of pH 4.0 showed the best results of adsorption, being obtained as the maximum adsorption capacity (q m ) and yield (%) (where q m = 87.95 mg g(-1) and 74.2%; 68.26 mg g(-1) and 68.6%; and 36.18 mg g(-1), 37.4%) of hydroxyapatite, synthetic hydroxyapatite, and active babassu coal, respectively. PMID- 27376150 TI - A Versatile Gene Delivery System for Efficient and Tumor Specific Gene Manipulation in vivo. AB - The Replication-Competent Avian Sarcoma-leukosis virus long-terminal repeat with splice acceptor (RCAS)-Tumor Virus A (TVA) gene delivery system has been created based on the fact that avian sarcoma leukosis virus subgroup A only infects cells expressing its receptor, TVA. This system has been successfully applied to create various mouse models for human cancers. Here we briefly discuss the advantages and the potential caveats of using this RCAS-TVA gene delivery system in cancer research. We also introduce and discuss how our newly designed RCAS-based gene delivery system (RCI-Oncogene, for RCAS-Cre-IRES-Oncogene) allows concise and efficient manipulation of gene expression in tumors in vivo, and how this system can be used to rapidly study the biological function of gene(s) and/or the collaborative actions of multiple genes in regulating tumor initiation, progression and/or metastasis. PMID- 27376151 TI - Malnutrition and Total Joint Arthroplasty. AB - Malnutrition is prevalent in patients undergoing elective total joint arthroplasty (TJA). Malnutrition has been shown to be an independent risk factor for multiple postsurgical complications following TJA in addition to increasing postoperative mortality. In the current healthcare environment, it is important to recognize and correct modifiable risk factors preoperatively to minimize perioperative complications and improve patient outcomes. Recently, multiple studies have been published focusing on the association between malnutrition and perioperative complications following TJA. The findings of these studies are summarized in this review. Further research is required to determine if optimization of nutritional status preoperatively influence surgical outcomes in the elective TJA patient. PMID- 27376152 TI - Whole-exome sequencing identifies ADRA2A mutation in atypical familial partial lipodystrophy. AB - Despite identification of causal genes for various lipodystrophy syndromes, the molecular basis of some peculiar lipodystrophies remains obscure. In an African American pedigree with a novel autosomal dominant, atypical familial partial lipodystrophy (FPLD), we performed linkage analysis for candidate regions and whole-exome sequencing to identify the disease-causing mutation. Affected adults reported marked loss of fat from the extremities, with excess fat in the face and neck at age 13-15 years, and developed metabolic complications later. A heterozygous g.112837956C>T mutation on chromosome 10 (c.202C>T, p.Leu68Phe) affecting a highly conserved residue in adrenoceptor alpha 2A (ADRA2A) was found in all affected subjects but not in unaffected relatives. ADRA2A is the main presynaptic inhibitory feedback G protein-coupled receptor regulating norepinephrine release. Activation of ADRA2A inhibits cAMP production and reduces lipolysis in adipocytes. As compared with overexpression of a wild-type ADRA2A construct in human embryonic kidney-293 cells and differentiated 3T3-L1 adipocytes, the mutant ADRA2A produced more cAMP and glycerol, which were resistant to the effects of the alpha2-adrenergic receptor agonist clonidine and the alpha2-adrenergic receptor antagonist yohimbine, suggesting loss of function. We conclude that heterozygous p.Leu68Phe ADRA2A mutation causes a rare atypical FPLD, most likely by inducing excessive lipolysis in some adipose tissue depots. PMID- 27376154 TI - Understanding the Importance of Gene and Environment in the Etiology and Prevention of Type 2 Diabetes Mellitus in High-Risk Populations. AB - Current literature focuses on the complications and treatment of Type 2 Diabetes Mellitus (T2DM) while clustering environmental and genetic factors to explain the disease. Interventions proposed to reduce diabetes prevalence should focus predominantly on initiating active rapports of family members and promoting a more communication-oriented preventative approach between diabetics and non diabetics. Due to varying risks in T2DM by race and ethnicity, these populations should follow race-appropriate guidelines to prevent further T2DM occurrence and complications. The review consists of information related to the genetic component of T2DM to help identify high-risk groups and focuses on the environmental aspect of the disease to help consider appropriate techniques to reduce disease burden. Genetic factors play important roles in the pathogenesis of diabetes and thus are an essential element of understanding the cause of the disease and possible methods of prevention. Focusing on high-risk groups with T2DM could have profound effects on the current health care situation. In this review, we discuss the epidemiology of diabetes in the United States and propose methods of preventing and delaying the development of T2DM in high-risk individuals. PMID- 27376153 TI - Temporal Regulation of the Bacillus subtilis Acetylome and Evidence for a Role of MreB Acetylation in Cell Wall Growth. AB - : Nepsilon-Lysine acetylation has been recognized as a ubiquitous regulatory posttranslational modification that influences a variety of important biological processes in eukaryotic cells. Recently, it has been realized that acetylation is also prevalent in bacteria. Bacteria contain hundreds of acetylated proteins, with functions affecting diverse cellular pathways. Still, little is known about the regulation or biological relevance of nearly all of these modifications. Here we characterize the cellular growth-associated regulation of the Bacillus subtilis acetylome. Using acetylation enrichment and quantitative mass spectrometry, we investigate the logarithmic and stationary growth phases, identifying over 2,300 unique acetylation sites on proteins that function in essential cellular pathways. We determine an acetylation motif, EK(ac)(D/Y/E), which resembles the eukaryotic mitochondrial acetylation signature, and a distinct stationary-phase-enriched motif. By comparing the changes in acetylation with protein abundances, we discover a subset of critical acetylation events that are temporally regulated during cell growth. We functionally characterize the stationary-phase-enriched acetylation on the essential shape-determining protein MreB. Using bioinformatics, mutational analysis, and fluorescence microscopy, we define a potential role for the temporal acetylation of MreB in restricting cell wall growth and cell diameter. IMPORTANCE: The past decade highlighted Nepsilon lysine acetylation as a prevalent posttranslational modification in bacteria. However, knowledge regarding the physiological importance and temporal regulation of acetylation has remained limited. To uncover potential regulatory roles for acetylation, we analyzed how acetylation patterns and abundances change between growth phases in B. subtilis. To demonstrate that the identification of cell growth-dependent modifications can point to critical regulatory acetylation events, we further characterized MreB, the cell shape-determining protein. Our findings led us to propose a role for MreB acetylation in controlling cell width by restricting cell wall growth. PMID- 27376155 TI - Co-Expression Network Analysis of Fbxw7-Associated LncRNAs Reveals Their Functions in Radiation-Induced Thymic Lymphoma. AB - FBXW7, an E3-ubiquitin protein ligase in SCFs (SKP1-cullin-F-box) complex, is a major human tumor suppressor gene, and understanding mechanisms by which FBXW7 contributes to tumorigenesis is critical for the treatment of human cancers with FBXW7 deficiency. Long non-coding RNAs (lncRNAs) have emerged as key regulators of various biological processes. Here we have identified a set of lncRNAs that are associated with Fbxw7 deficiency. The correlation network and functional annotation analysis revealed that Fbxw7-associated lncRNAs regulate genes involved in cell cycle, DNA repair, metabolic process, and cell communication and adhesion. The number of coding genes that correlated with individual lncRNAs varied largely. A lncRNA on chromosome 15 (A_30_P01032978), which was upregulated in tumors from Fbxw7 deficient mice was positively correlated with 15 coding genes. High expression of this 15-gene signature was associated with poor prognosis in two independent human breast cancer studies. Our results open possible new avenues to understand mechanisms by which Fbxw7 deficiency increases tumor susceptibility via the alteration of lncRNAs. PMID- 27376156 TI - DNA-PK Deficiency in Alzheimer's Disease. AB - Alzheimer's disease (AD) is characterized by neuronal death with an accumulaton of intra-cellular neurofibrillary tangles (NFT) and extracellular amyloid plaques. Reduced DNA repair ability has been reported in AD brains. In neurons, the predominant mechanism to repair double-strand DNA breaks (DSB) is non homologous end joining (NHEJ) that requires DNA-dependent protein kinase (DNA-PK) activity. DNA-PK is a holoenzyme comprising the p460 kD DNA-PK catalytic subunit (DNA-PKcs) and its activator Ku, a heterodimer of p86 (Ku80) and p70 (Ku70) subunits. Upon binding to double-stranded DNA ends, Ku recruits DNA-PKcs to process NHEJ. In AD brains, reduced NHEJ activity as well as DNA-PKcs and Ku protein levels have been shown. Normal aging brains also show a reduction in both DNA-PKcs and Ku levels questioning a direct link between NHEJ ability and AD, and suggesting additional players/events in AD pathogenesis. Deficiency of Ku80, a somatostatin receptor, can disrupt somatostatin signaling thus inducing amyloid beta (Abeta) generation, which in turn can potentiate DNA-PKcs degradation and consequently loss of NHEJ activity, an additional step negatively affecting DSB repair. Trigger of these two different pathways culminating in genome instability may differentiate the outcomes between AD and normal aging. PMID- 27376157 TI - MicroRNA-124 suppresses tumor cell proliferation and invasion by targeting CD164 signaling pathway in non-small cell lung cancer. AB - MicroRNAs play critical roles in regulating gene expression and various cellular processes in human cancer malignant progression. Down-regulated expression of miR 124 gene has been shown to be significantly associated with a poor prognosis in patients with non-small cell lung cancer (NSCLC) but its biological function and regulatory roles in lung cancer tumorigenesis are largely unknown. In this study, we aimed to determine effects of ectopic expression of miR-124 on tumor cell proliferation, invasion, and induction of apoptosis by DOTAP:Cholesterol nanoparticle-mediated gene transfer and identify its endogenous targets under physiological conditions in NSCLC cells. Overexpression of miR-124 significantly suppresses tumor cell proliferation, colony formation, migration, and induction of apoptosis in H322 and A549 cells. Two endogenous miR-124 targeting sites in the 3'UTR of CD164 mRNA are identified by a stem-loop-array reverse transcription PCR (SLA-RT-PCR) assay in H1299 cells under physiological condition. Ectopic expression of miR-124 induces CD164 mRNA cleavage and down-regulated its gene and protein expression. Our results suggest that miR-124 function as a tumor suppressor miRNA and suppress tumor proliferation and aggression by directly targeting oncogenic CD164 signaling pathway in NSCLC. PMID- 27376158 TI - Identity Management and Mental Health Discourse in Social Media. AB - Social media is increasingly being adopted in health discourse. We examine the role played by identity in supporting discourse on socially stigmatized conditions. Specifically, we focus on mental health communities on reddit. We investigate the characteristics of mental health discourse manifested through reddit's characteristic 'throwaway' accounts, which are used as proxies of anonymity. For the purpose, we propose affective, cognitive, social, and linguistic style measures, drawing from literature in psychology. We observe that mental health discourse from throwaways is considerably disinhibiting and exhibits increased negativity, cognitive bias and self-attentional focus, and lowered self-esteem. Throwaways also seem to be six times more prevalent as an identity choice on mental health forums, compared to other reddit communities. We discuss the implications of our work in guiding mental health interventions, and in the design of online communities that can better cater to the needs of vulnerable populations. We conclude with thoughts on the role of identity manifestation on social media in behavioral therapy. PMID- 27376159 TI - A systematic review of lifestyle interventions for chronic diseases in rural communities. AB - BACKGROUND: Rural Americans suffer disproportionately from lifestyle-related chronic diseases (e.g., obesity, diabetes, hypertension, cardiovascular disease, and breast cancer). Interventions that consider the distinctive characteristics of rural communities (e.g., access to healthcare, income, and education) are needed. As an initial step in planning future research, we completed a systematic review of dietary intake and physical activity interventions targeting rural populations. METHODS: Manuscripts focused on dietary intake and physical activity and published through March 15, 2016, were identified by use of PubMed and CINAHL databases and MeSH terms and keyword searches. RESULTS: A total of 18 studies met the inclusion criteria. Six involved randomized controlled trials; 7 used quasi experimental designs; 4 had a pre-/post-design; and 1 was an observational study. Eight studies were multi-site (or multi-county), and 3 focused on churches. Primary emphasis by racial/ethnic group included: African Americans (6); Whites (2); Hispanics (3); and two or more groups (7). Most studies (17) sampled adults; one included children. Two studies targeted families. CONCLUSIONS: Additional lifestyle intervention research is needed to identify effective approaches promoting healthy diet and exercise and chronic disease prevention in rural communities. Studies that include rigorous designs, adequate sample sizes, and generalizable results are needed to overcome the limitations of published studies. PMID- 27376160 TI - Asfotase alfa: enzyme replacement for the treatment of bone disease in hypophosphatasia. AB - Hypophosphatasia (HPP) is a rare disease caused by loss-of-function mutations in the tissue-nonspecific alkaline phosphatase (TNAP, TNSALP) gene. HPP causes a multisystemic syndrome with a predominant bone phenotype. The clinical spectrum ranges from high lethality in early onset (<6 months) HPP to mild late-onset syndromes. HPP management so far has been only supportive. Subcutaneous asfotase alfa, a first-in-class bone-targeted human TNAP enzyme replacement therapy, is the first compound to be approved for long-term treatment of bone manifestations in pediatric-onset HPP. In noncomparative clinical trials (treatment up to 7 years), this treatment was associated with skeletal, respiratory and functional improvement in perinatal, infantile and childhood-onset HPP. Compared with age matched historical controls, patients with life-threatening perinatal and infantile HPP treated with asfotase alfa had substantially improved bone mineralization, survival and ventilation-free survival. In childhood HPP, asfotase alfa improved growth, gross motor function, strength and agility and decreased pain. The compound was well tolerated and most adverse events were of mild to moderate intensity. To date, data and experience concerning its efficacy and safety in long-term treatment are not yet available. Further studies to evaluate risks and benefits of enzyme replacement therapy with asfotase alfa in adults are in progress and are also strongly needed. PMID- 27376161 TI - Sebelipase alfa: enzymatic replacement treatment for lysosomal acid lipase deficiency. AB - Sebelipase alfa was approved for use in 2015 for patients suffering from lysosomal acid lipase deficiency in either of its two forms. The more severe, early-onset form, Wolman disease, occurs in young infants in whom it is normally fatal within the first year of life. Sebelipase alfa has allowed a small number of such infants to achieve a relatively normal growth rate and to survive for 2 or more years. In older children and adults, the enzyme has corrected their dyslipidemia and produced significant improvement in markers of hepatic function. Important unanswered questions remain, such as to what extent treatment with sebelipase alfa alters the long-term cardiovascular and hepatic consequences of this rare recessive genetic disorder. Further research is also required to determine the true frequency of the disorder in different populations and ethnic groups. The high cost of treatment with sebelipase alfa also poses a very significant obstacle for many health plans. PMID- 27376162 TI - Sonidegib phosphate: new approval for basal cell carcinoma. AB - Basal cell carcinoma (BCC), although mostly locally confined, is the most common cancer. Most BCCs harbor inactivating mutations in the membrane receptor/gene Ptch, thereby activating the Hedgehog signaling pathway (Hh) via the essential signaling molecule Smoothened (SMO). Novel small-molecule inhibitors or antagonists of SMO have shown excellent response rates in patients with locally advanced, unresectable and metastatic BCC in roughly 35-60% of patients, with disease control rates and clinical benefit being even higher. Sonidegib is the second-in-class SMO inhibitor approved for locally advanced, unresectable and metastatic BCC. Sonidegib is given once daily continuously, with specific side effects as listed in the label indication. Resistance develops over time and knowledge gleaned from other SMO inhibitors indicates that SMO mutations preventing drug binding as well as mechanisms activating the Hh pathway downstream of SMO are responsible, ultimately reactivating Hh pathway signaling. The next challenge will be to define novel salvage and SMO combination strategies for BCC and other tumors. PMID- 27376163 TI - 28th Annual DIA EuroMeeting (April 6-8, 2016 - Hamburg, Germany). AB - The 28(th) Drug Information Association (DIA) Annual EuroMeeting took place in Hamburg, Germany, gathering together participants from different industries, organizations, academic research centers, regulatory agencies and health ministries, mainly from the E.U. The conference began with a regulatory Town Hall meeting focusing on the E.U. Medicines Agencies Network strategy to 2020. This was followed by an opening plenary session where the diverse roles of innovation in drug development were discussed. Areas for discussion over the meeting were classified into 14 main themes, and for each session, profession!als from the pharmaceutical industry, regulatory agencies and health ministries, as well as delegates from patient organizations, presented their considerations for debate. This report covers some regulatory sessions presented at the meeting. PMID- 27376164 TI - Biosimilar Medicines Group - 14th Annual Medicines for Europe Conference (April 28-29, 2016 - London, UK). AB - Biotechnology has enabled the development of treatments for many diseases benefiting millions of people. Similar biologics or 'biosimilar' versions of originator biologic medicines are a relatively new category of biologics, usually developed when the originator is protected by patent exclusivity and introduced to healthcare systems as a cheaper option to treat disease. Biosimilars provide value and thus access for new groups of patients because they bring cost savings to the healthcare ecosystem. Generics achieved cost savings of EUR 100 billion in 2014, which allows the system to finance more innovative methods of bringing medicines to patients. The Medicines for Europe Biosimilars Medicines Group Conference in London is the main annual biosimilars gathering and attracts the world's experts. A recurring theme throughout this year's conference was the promotion of a multi-stakeholder approach; if stakeholders work together they will collectively give patients more opportunity to benefit from biologic medicines. In discussion were the latest developments in the biosimilars market, including the ongoing challenges against adoption of biosimilars. PMID- 27376165 TI - American Urological Association (AUA) - 111th Annual Meeting (May 6-10, 2016 - San Diego, California, USA). AB - The 111(th) Annual Meeting of the American Urological Association (AUA) brought together a wide range of researchers in the field of urology to share knowledge and set standards in urological research. The meeting consisted of plenary, podium and moderated poster sessions, in which the latest research and advances in urologic medicine were presented. This report will highlight some of the presentations on therapeutic developments for a range of urological conditions. PMID- 27376166 TI - Electrostatic gating in carbon nanotube aptasensors. AB - Synthetic DNA aptamer receptors could boost the prospects of carbon nanotube (CNT)-based electronic biosensors if signal transduction can be understood and engineered. Here, we report CNT aptasensors for potassium ions that clearly demonstrate aptamer-induced electrostatic gating of electronic conduction. The CNT network devices were fabricated on flexible substrates via a facile solution processing route and non-covalently functionalised with potassium binding aptamers. Monotonic increases in CNT conduction were observed in response to increasing potassium ion concentration, with a level of detection as low as 10 picomolar. The signal was shown to arise from a specific aptamer-target interaction that stabilises a G-quadruplex structure, bringing high negative charge density near the CNT channel. Electrostatic gating is established via the specificity and the sign of the current response, and by observing its suppression when higher ionic strength decreases the Debye length at the CNT water interface. Sensitivity towards potassium and selectivity against other ions is demonstrated in both resistive mode and real time transistor mode measurements. The effective device architecture presented, along with the identification of clear response signatures, should inform the development of new electronic biosensors using the growing library of aptamer receptors. PMID- 27376167 TI - 'Accepting where I'm at' - a qualitative study of the mechanisms, benefits, and impact of a behavioral memory intervention for community-dwelling older adults. AB - OBJECTIVE: Gain novel, in-depth insight into therapeutic mechanisms, benefits, and impact of a multi-modal behavioral memory intervention for older adults with concerns about memory. METHODS: Participants were11 community-dwelling older adults (aged 63-88) who completed the Memory and Aging Program, an evidence-based multi-modal group intervention for normal age-related memory change. Semi structured interviews were administered post-intervention. Responses were analyzed using qualitative content analysis until meaningful themes were agreed upon. RESULTS: Analyses revealed a main theme of normalization as the overarching benefit of participation. The mechanism for this comprised both specific intervention content and the process of participating with others. A positive impact of the intervention was demonstrated at emotional (feelings of reassurance, hope, and confidence) and functional (increasing motivation for lifestyle change) levels; for some, there was a direct link between emotion and function. CONCLUSION: This study highlighted a single, prominent therapeutic benefit of normalization, illustrated a dual mechanism for achieving this, and characterized a nuanced inter-relationship of the emotional and functional impact of the intervention for participants. Results support the notion that group behavioral interventions can educate, empower, and promote psychological well being in older adults and may be an effective avenue to reduce risk of disease and promote sustained functional independence. PMID- 27376168 TI - Challenges faced in long term ventricular assist device support. AB - INTRODUCTION: The development of ventricular assist device (VAD) has been one of the revolutionary advancements in end-stage heart failure management. Although the device has developed and improved significantly over the last few decades, we still face multiple challenges. AREAS COVERED: This review will discuss quality of life, survival, and clinically encountered complications in patients with VAD support. The literature was extensively reviewed for studies describing the above topic area. We describe the impact of major challenges faced in VAD support and discuss their future and expectations. Expert commentary: The technological advancement of VADs has contributed to major improvement of overall survival, enhancement of quality of life and decrease of incidence of complications. It is expected that technologies will continue to evolve. At the same time, the indications for and timing of device implantation, and selection of device type are continuously important in clinical practice setting. PMID- 27376169 TI - Caregiving styles and anxiety among couples: coping versus not coping with cardiac illness. AB - BACKGROUND AND OBJECTIVES: partners' caregiving efforts are not always beneficial to both recipient and provider. Bowlby's conceptualization of caregiving style as a stable predisposition may clarify such caregiving effects. The relationship between caregiving style (compulsive and sensitive) and anxiety among couples coping with cardiac illness and a matching control group not coping with cardiac illness were assessed. We hypothesized that one's compulsive caregiving would associate positively, and one's sensitive caregiving would associate negatively, with one's and one's partner's anxiety across contexts (cardiac and non-cardiac) and gender. DESIGN: A comparative design of 131 couples with a diagnosis of husbands' acute cardiac syndrome and 68 matched couples in the community was applied. METHODS: The Adult Caregiving Questionnaire and the Brief Symptoms Inventory were administered. RESULTS: Structural equation modeling revealed that one's compulsive caregiving was positively associated with one's anxiety, across most contexts. Multi-group analyses revealed that the associations between one's compulsive caregiving and one's partner's anxiety levels differed depending on gender and context. CONCLUSIONS: The distress which emerges in an individual who takes on a caregiving role and in his/her partner seems to result not only from the demands of the concrete caregiving situation but also from one's and one's partner's developmental history. PMID- 27376171 TI - Psychosocial stress based on public speech in humans: is there a real life/laboratory setting cross-adaptation? AB - Repeated or chronic exposure to stressors is associated with changes in neuroendocrine responses depending on the type, intensity, number and frequency of stress exposure as well as previous stress experience. The aim of the study was to test the hypothesis that salivary cortisol and cardiovascular responses to real-life psychosocial stressors related to public performance can cross-adapt with responses to psychosocial stress induced by public speech under laboratory setting. The sample consisted of 22 healthy male volunteers, which were either actors, more precisely students of dramatic arts or non-actors, students of other fields. The stress task consisted of 15 min anticipatory preparation phase and 15 min of public speech on an emotionally charged topic. The actors, who were accustomed to public speaking, responded with a rise in salivary cortisol as well as blood pressure to laboratory public speech. The values of salivary cortisol, systolic blood pressure and state anxiety were lower in actors compared to non actors. Unlike non-actors, subjects with experience in public speaking did not show stress-induced rise in the heart rate. Evaluation of personality traits revealed that actors scored significantly higher in extraversion than the subjects in the non-actor group. In conclusion, neuroendocrine responses to real life stressors in actors can partially cross-adapt with responses to psychosocial stress under laboratory setting. The most evident adaptation was at the level of heart rate responses. The public speech tasks may be of help in evaluation of the ability to cope with stress in real life in artists by simple laboratory testing. PMID- 27376172 TI - Cooking and coughing: Estimating the effects of clean fuel for cooking on the respiratory health of children in the Philippines. AB - Household air pollution (HAP) arising from the use of solid fuels for cooking is known to have adverse health effects including acute respiratory infections in children, which remains a major public health concern in developing countries. Hence, various interventions to reduce HAP have been advocated or piloted in many countries. To provide additional evidence on the effectiveness and applicability of the interventions in various settings, we investigate the effects of clean fuel for cooking on the risks of respiratory illness of children below five years old in the Philippines. We apply the propensity score matching method on a subsample of households culled from the 2013 round of the National Demographic and Health Survey to account for the systematic differences in their characteristics that could influence their choices of cooking fuel. We find that the use of electricity, liquefied petroleum gas, natural gas or biogas can lower by 2.4 percentage points the incidence of severe coughing with difficulty in breathing in young children. Our results support worldwide initiatives to promote the household use of clean fuels for cooking and heating to reduce HAP and its undesirable impacts on population health. PMID- 27376170 TI - Advances in PET/MR instrumentation and image reconstruction. AB - The combination of positron emission tomography (PET) and MRI has attracted the attention of researchers in the past approximately 20 years in small-animal imaging and more recently in clinical research. The combination of PET/MRI allows researchers to explore clinical and research questions in a wide number of fields, some of which are briefly mentioned here. An important number of groups have developed different concepts to tackle the problems that PET instrumentation poses to the exposition of electromagnetic fields. We have described most of these research developments in preclinical and clinical experiments, including the few commercial scanners available. From the software perspective, an important number of algorithms have been developed to address the attenuation correction issue and to exploit the possibility that MRI provides for motion correction and quantitative image reconstruction, especially parametric modelling of radiopharmaceutical kinetics. In this work, we give an overview of some exemplar applications of simultaneous PET/MRI, together with technological hardware and software developments. PMID- 27376173 TI - Metaproteomic data analysis at a glance: advances in computational microbial community proteomics. AB - INTRODUCTION: Within the last decade, the study of microbial communities has gained increasing research interest also driven by the recognition of the important role of these consortia in human health and disease. Metaproteomics, the analysis of the entire set of proteins from all microorganisms present in one ecosystem, has become a prominent technique for studying the relation between taxonomic diversity and functional profile of microbial communities. AREAS COVERED: The aim of this review is to address opportunities and challenges of metaproteomics from a computational perspective. Appealing to an audience of microbial ecologists and proteomic researchers alike, we provide an overview on state-of-the-art software and databases by which metaproteome data can be readily analyzed. Expert commentary: While tailored protein databases, combined search algorithms and iterative workflows are means to improve the identification yield, software tools for taxonomic and functional analysis are challenged by the vast amount of unannotated sequences in metaproteomics. PMID- 27376174 TI - The effect of pavement markings on driving behaviour in curves: a simulator study. AB - This study investigates the effect of two pavement markings (transverse rumble strips (TRS) and a backward pointing herringbone pattern (HP)) on speed and lateral control in and nearby curves. Two real-world curves with strong indications of a safety problem were replicated as realistic as possible in the simulator. Results show that both speed and lateral control differ between the curves. These behavioural differences are probably due to curve-related dissimilarities with respect to geometric alignment, cross-sectional design and speed limit. TRS and HP both influenced mean speed and mean acceleration/deceleration but not lateral control. TRS generated an earlier and more stable speed reduction than HP which induced significant speed reductions along the curve. The TRS gives drivers more time to generate the right expectations about the upcoming curve. When accidents occur primarily near the curve entry, TRS is recommended. The HP has the potential to reduce accidents at the curve end. Practitioner Summary: Two pavement markings (transversal rumble strips and HP) nearby dangerous curves were investigated in the driving simulator. TRS generated an earlier and more stable speed reduction than HP which induced speed reductions along the curve. The TRS gives drivers more time to generate right expectations about the upcoming curve. PMID- 27376175 TI - Non-fatal strangulation in sexual assault: A study of clinical and assault characteristics highlighting the role of intimate partner violence. AB - OBJECTIVE: To describe the prevalence, risk factors, signs and symptoms of non fatal strangulation (NFS) in women referred to a Sexual Assault Resource Centre (SARC) following recent sexual assault. METHODS: A cross-sectional study using data routinely collected at time of forensic examination of women (age >= 13 years) referred to the Western Australian SARC between Jan-2009 and Mar-2015 alleging a recent sexual assault. Data on demographics, assault characteristics and forensic findings were available. RESULTS: A total of 1064 women were included in the study; 79 (7.4%) alleged NFS during the sexual assault. The prevalence of NFS varied significantly by age-group and assailant type. Of women aged 30-39 years 15.1% gave a history of NFS compared to less than 8.2% in all other age groups. Of women assaulted by an intimate partner, 22.5% gave a history of NFS compared to less than 6% of women assaulted by other assailant types. Of all sexual assaults with NFS, intimate partners were the assailant in 58.2% of cases, whereas in sexual assault cases without NFS, intimate partners were the assailant in 15.9% of cases. Odds of NFS were 8.4 times higher in women sexually assaulted by an intimate partner compared to women assaulted by an acquaintance/friend and 4.9 times higher compared to women assaulted by a stranger. When considering both age and assailant type the highest proportion of NFS (33.9%) was in women aged 30-39 years sexually assaulted by an intimate partner. Other factors associated with NFS during sexual assault included deprivation of liberty, verbal threats, being assaulted in the woman's home and use of additional blunt force. External physical signs of NFS were absent in 49.4% of all NFS sexual assault cases. CONCLUSIONS: This study identifies and quantifies NFS risk factors in female sexual assault and highlights the strong association with intimate partner sexual assault. Greater awareness of NFS in sexual assault should lead to improvement in medical screening, forensic management and safety risk assessment by sexual assault and domestic violence services, emergency departments and police. PMID- 27376176 TI - Legends about Legends: Abraham Eleazar's Adaptation of Nicolas Flamel. AB - This paper explores the relationship between three illustrated alchemical treatises, all of which are associated with Jewish adepts: the famous Le Livre des figures hieroglyphiques attributed to Nicolas Flamel, and two treatises published in 1735 in Erfurt-the Uraltes Chymisches Werckh and the Donum Dei. The Werckh is supposedly written by Rabbi Abraham Eleazar, while the Donum Dei is attributed to an ancient alchemist-cabalist, Rabbi Samuel Baruch. I argue that these authors are fictitious, and that both works were in fact written in the early eighteenth century by their supposed editor, the probably pseudonymous Julius Gervasius. Gervasius connects the Werckh with the legend of Nicolas Flamel by suggesting that it is based on the original, Jewish manuscript which helped Flamel to find the Stone of the Sages. Gervasius used various strategies to confer a sense of Jewish "authenticity" on these works, borrowing from contemporary (non-Jewish) perceptions of Jewish ritual, Hebrew language, and Christian Cabala. The Werckh also borrows and adapts a sequence of allegorical illustrations from those in pseudo-Flamel's Livre, and I compare the two sets of figures and, where possible, interpret them. I conclude that the later works in fact teach us far more about the state of alchemy in the seventeenth and eighteenth centuries than they do about either medieval alchemy or Judaism. PMID- 27376177 TI - Polyurethane Foam-Based Ultramicroporous Carbons for CO2 Capture. AB - A series of sustainable porous carbon materials were prepared from waste polyurethane foam and investigated for capture of CO2. The effects of preparation conditions, such as precarbonization, KOH to carbon precursor weight ratio, and activation temperature, on the porous structure and CO2 adsorption properties were studied for the purpose of controlling pore sizes and nitrogen content and developing high-performance materials for capture of CO2. The sample prepared at optimum conditions shows CO2 adsorption capacities of 6.67 and 4.33 mmol.g(-1) at 0 and 25 degrees C under 1 bar, respectively, which are comparable to those of the best reported porous carbons prepared from waste materials. The HCl treatment experiment reveals that about 80% of CO2 adsorption capacity arises from physical adsorption, while the other 20% is due to the chemical adsorption originated from the interaction of basic N groups and CO2 molecules. The relationship between CO2 uptake and pore size at different temperatures indicates that the micropores with pore size smaller than 0.86 and 0.70 nm play a dominant role in the CO2 adsorption at 0 and 25 degrees C, respectively. It was found that the obtained carbon materials exhibited high recyclability and high selectivity to adsorption of CO2 from the CO2 and N2 mixture. PMID- 27376178 TI - The influence of the human TMJ eminence inclination on predicted masticatory muscle forces. AB - Aim of this paper was to investigate the change in masticatory muscle forces and temporomandibular joint (TMJ) reaction forces simulated by inverse dynamics when thesteepness of the anterior fossa slope was varied. We used the model by de Zee et al. (2007) created in AnyBodyTM. The model was equipped with 24musculotendon actuators. Mandibular movement was governed by thetrajectory of theincisal point. The TMJ was modelled as a planar constraint canted 5 degrees medially and thecaudal inclination relative to the occlusal plane was varied from 10 degrees to 70 degrees . Our models showed that for the two simulated movements (empty chewing and unilateral clenching) the joint reaction forces were smallest for the eminence inclination of 30 degrees and 40 degrees and highest for 70 degrees . The muscle forces were relatively insensitive to change of the eminence inclination for the angles between 20 degrees and 50 degrees . This did not hold for the pterygoid muscle, for which the muscle forces increased continually with increasing fossa inclination. For empty chewing the muscle force reached smaller values than for clenching. During clenching, the muscle forces changed by up to 200N. PMID- 27376179 TI - Gnathodiaphyseal Dysplasia: Surgical Treatment and Prosthetic Rehabilitation of 2 Members of the Same Family. AB - Gnathodiaphyseal dysplasia (GDD) is a rare hereditary syndrome characterized by cemento-ossifying fibromas of the maxillary bones, fragile bones, curvature and cortical thinning of the tubular bones, and diaphyseal sclerosis of the long bones. In this study, 2 complex clinical cases of 2 members of the same family had GDD and were treated in the authors' odonto-stomatology department. The first was treated with a block bone graft and implant-prosthetic therapy; the other, who had extensive osteomyelitis of the second quadrant, was managed with extraction of the involved teeth, surgical revision of the site, and a graft of autologous platelet concentrate. PMID- 27376181 TI - Unusual Presentation of an Adenocarcinoma of the Lung Metastasizing to the Mandible, Including Molecular Analysis and a Review of the Literature. AB - Lung cancer is the most frequent cause of cancer-related death worldwide. Metastases of non-small cell lung carcinoma to the oral and maxillofacial region are rare. Thus, the diagnosis of a metastatic lesion in the oral cavity is challenging to the clinician and to the pathologist. This report presents a case of a 72-year-old man with metastatic lung adenocarcinoma located in the posterior mandibular region. Next-generation sequencing analysis showed no important mutations in the relevant genes except in the TP53 tumor suppressor gene. PMID- 27376180 TI - Patients Receiving Parenteral Bisphosphonates for Malignant Disease and Having Developed an Atypical Femoral Fracture Are at Risk of Concomitant Osteonecrosis of the Jaw: An Evidence-Based Review. AB - PURPOSE: The risk of developing concomitant medication-related osteonecrosis of the jaw (MRONJ) in patients who have sustained an atypical femoral fracture (AFF) in association with parental administration of a bisphosphonate osteoclastic inhibitor medication for malignant disease is unclear. Published data were searched to determine the prevalence of these concomitant adverse medication events, if any. MATERIALS AND METHODS: A systematic review of published case series in the PubMed database was undertaken to ascertain the prevalence of patients having a concomitant history of AFF and MRONJ. The data were analyzed to provide prevalence rates of these events from the literature. RESULTS: Two case series were identified that delineated the risk (25 and 33%, respectively) of concomitant development of MRONJ and AFF in recipients of parenteral bisphosphonate medication administered for malignant disease. CONCLUSION: The published data suggest that approximately 30% of patients receiving parenteral bisphosphonates and having sustained an AFF could develop comorbid MRONJ. PMID- 27376182 TI - Outcomes of Immediate Allograft Reconstruction of Long-Span Defects of the Inferior Alveolar Nerve. AB - PURPOSE: Contemporary management of ablative jaw defects includes not only hard and soft tissue reconstruction, but also restoration of neurosensory function. The goal of this study was to determine the outcomes of immediate reconstruction of long-span defects (>=50 mm) of the inferior alveolar nerve (IAN) after ablative mandibular resection using allogeneic nerve grafts. MATERIALS AND METHODS: A retrospective cohort study of patients who underwent immediate reconstruction of IAN gaps of at least 50 mm with allogeneic nerve graft (AxoGen Avance, Alachua, FL) at a single academic medical center by a single surgeon (M.M.) from September 2013 to March 2015 was completed. Demographic and clinical data were collected for each patient and analyzed using clinical neurosensory testing and were reported using the Medical Research Council Scale (MRCS) for functional sensory recovery. In addition, patient subjective perception of neurosensory recovery was recorded using a visual analog scale (VAS). Subjective (VAS) and objective (MRCS) measurements of functional sensory recovery were recorded and compared across the study population. In addition, examined demographic and clinical data included patient age, gender, pathology, length of nerve allograft, and follow-up period. RESULTS: Of 12 with nerve repairs, 7 patients met the inclusion criteria. The average age was 34.7 years (range, 18 to 61 yr) and 71.4% were men. All IAN defects resulted from resection of mandibular pathology (6 benign lesions, 1 malignant lesion). Six of the 7 IAN defects were reconstructed with a 70-mm nerve allograft, and 1 nerve defect was reconstructed with a 50-mm graft. Mean follow-up time was 17.7 months (range, 10 to 27.5 months). Mean VAS score reported was 3.7 (range, 0 to 7). In addition, 85.7% of patients displayed return of some superficial pain and tactile sensation without over-response (S3), with 14.3% displaying good stimulation localization (S3+). The patient who displayed S3+ recovery underwent reconstruction with the 50-mm graft. Only 1 of the 7 patients had no neurosensory recovery (S0). CONCLUSIONS: Immediate reconstruction of the IAN with allogeneic nerve grafting of long-span defects (>=5 cm) is a viable and predictable option to achieve useful functional sensory recovery. PMID- 27376184 TI - Does Injection of Corticosteroid After Arthrocentesis Improve Outcomes of Temporomandibular Joint Osteoarthritis? A Randomized Clinical Trial. AB - PURPOSE: The purpose of this study is to answer the following clinical question: Among patients with temporomandibular joint (TMJ) osteoarthritis (OA), do those undergoing arthrocentesis and corticosteroid (CS) injection, when compared with those undergoing arthrocentesis alone, have better outcomes in terms of range of motion and clinical symptoms? MATERIALS AND METHODS: A randomized clinical trial in adult patients with TMJ OA referred to our clinic between May 2012 and September 2013 was implemented. The sample was composed of 24 consecutive patients with TMJ OA treated randomly with either arthrocentesis alone (control group) or arthrocentesis plus CS injection (CS group). The outcome variables were visual analog scale evaluations (ie, masticatory efficiency, joint sounds, and pain complaints), maximal interincisal opening, and mandibular motions. The outcome variables were recorded at baseline and at 12 months postoperatively. The Mann-Whitney U test was used for intergroup comparison. The paired t test and Wilcoxon signed rank test were used for intragroup comparisons. RESULTS: The sample was composed of 32 joints in 24 patients with TMJ OA (15 joints in 12 patients with a mean age of 35.08 +/- 14.84 years comprising the control group and 17 joints in 12 adult patients with a mean age of 32.58 +/- 9.58 years comprising the CS group). Pain complaints and joint sounds showed statistically significant decreases (P < .01) in both groups, whereas painless interincisal opening showed a statistically significant increase (P < .001) in only the CS group. After estimation of differences between the follow-up and baseline outcomes, the mean change in the primary outcome variables showed no statistically significant differences between the 2 groups (P > .05). CONCLUSIONS: These findings suggest that arthrocentesis plus intra-articular CS injection produced no better outcomes in terms of range of motion and clinical symptoms in patients with TMJ OA, as compared with those undergoing arthrocentesis alone. PMID- 27376183 TI - Changes in Peri-Implant Bone Level and Effect of Potential Influential Factors on Dental Implants in Irradiated and Nonirradiated Patients Following Multimodal Therapy Due to Head and Neck Cancer: A Retrospective Study. AB - PURPOSE: The aim of the present study was to evaluate changes in the marginal bone level of dental implants in irradiated and nonirradiated patients and to identify possible influential factors. MATERIALS AND METHODS: Thirty-six patients with 194 implants were involved in the study (7 women and 29 men). The mean age of the patients was 65.8 years (39 to 90 yr). In all patients, a squamous cell carcinoma in the floor of the mouth involving the mandible or tongue was surgically removed. In 17 patients, adjuvant radiochemotherapy was completed a minimum of 6 months before implant placement. Mean crestal bone changes using standardized orthopantomographs were evaluated. The Spearman rank-order correlation coefficient and Mann-Whitney U test were used to determine correlations between bone crestal changes and age, gender, radiation therapy (yes vs no), augmentation (yes vs no), and type of superstructure. RESULTS: In total, 194 implants were placed (73 in the maxilla and 121 in the mandible). Mean amounts of peri-implant bone loss were 1 mm mesially and 0.9 mm distally after 1 year and 1.4 mm mesially and 1.3 mm distally after 3 years. During the observation period, 4 implants were lost. The overall success rate was 98.4% (maxilla, 100%; mandible, 96.7%). There was no relevant difference in changes in bone level according to age, gender, prosthetic superstructure, or augmentation procedure (yes vs no). Radiation therapy was found to have an effect on crestal bone loss. CONCLUSION: The present study showed a high success rate of dental implants after 3 years. Peri-implant crestal bone loss was comparable to that in patients without tumor. The mean amount of crestal bone change in irradiated patients was twice as high as that in nonirradiated patients. PMID- 27376185 TI - Homozygous familial hypercholesterolaemia in two boys aged 5 and 10 years. AB - Familial hypercholesterolaemia (FH) is an autosomal dominant lipid disorder. Homozygous FH (HFH), though rare, presents in early childhood. Two different presentations of HFH are reported. The first child presented at 5 years of age with xanthomas on the knees, elbows and buttocks and failure to thrive since the second year of life. He was found to be hypertensive with moderate aortic regurgitation. He is now stable on statins and antihypertensives. The second child presented at 10 years of age with multiple xanthomas and severe aortic stenosis. He died of refractory cardiac failure despite emergency aortic balloon valvoplasty due to diffuse coronary artery disease. Strong clinical suspicion can aid early diagnosis and delay cardiovascular complications. PMID- 27376186 TI - Come to think of it: Contributions of reasoning abilities and training schedule to skill acquisition in a virtual throwing task. AB - According to Schmidt's schema theory skill acquisition is based on schema formation where multiple learning incidents with varying task features are abstracted to a unifying pattern, the schema. Practice can be scheduled block wise, with low contextual interference (CI) or randomly, with high CI. The greater effort during high CI training usually results in reduced training success but enhanced retention and transfer performance. In contrast to well established CI effects for simple tasks, findings for complex tasks are heterogeneous, supposedly due to the detrimental accumulation of task demands. We assumed that in complex tasks, cognitive reasoning abilities might impose a limit upon schema formation and hence the effectiveness of CI. In a virtual overarm throwing experiment participants practiced target positions at center, left, or right and were retested for retention - at the center position - and transfer with a larger target distance. Although there was no main effect of CI on performance, either in training, retention or transfer, under high CI, training performance was better for participants with higher reasoning ability, as measured with the Raven matrices. This advantage persisted across retention and transfer. Under low CI, reasoning was positively related to performance improvement only in the last third of training. We argue, that variability of practice is a necessary prerequisite for beneficial effects of reasoning abilities. Based on previous findings, we discuss feedback evaluation as a possible locus of the relationship between reasoning and performance in motor skill acquisition. PMID- 27376187 TI - Age-related differences in task switching and task preparation: Exploring the role of task-set competition. AB - The present study focused on the role of task preparation in age-related task switching deficits. In Experiment 1, we assessed the preparatory reduction of alternation costs (i.e., alternating-task conditions vs. single-task conditions) in twenty-two older adults (65-78years) and 22 young adults (20-28years) by varying the response-stimulus interval (RSI) in a task-switching paradigm with a predictable task sequence and univalent stimuli. In Experiment 2, in which new groups of 22 older adults (65-78years) and 22 young adults (18-24years) took part, we replicated Experiment 1 with bivalent stimuli, which were associated with both tasks and thus increased task-set competition. Whereas in Experiment 1, in which we used univalent stimuli, there were no age-related differences in the preparatory reduction of alternation costs, the data showed impaired task preparation in old age with bivalent stimuli in Experiment 2. These data support the notion that task-preparation deficits in old age occur particularly in situations of increased task-set competition. PMID- 27376188 TI - Allogeneic mesenchymal precursor cells (MPCs): an innovative approach to treating advanced heart failure. AB - INTRODUCTION: Over 37 million people worldwide are living with Heart Failure (HF). Advancements in medical therapy have improved mortality primarily by slowing the progression of left ventricular dysfunction and debilitating symptoms. Ultimately, heart transplantation, durable mechanical circulatory support (MCS), or palliative care are the only options for patients with end stage HF. Regenerative therapies offer an innovative approach, focused on reversing myocardial dysfunction and restoring healthy myocardial tissue. Initial clinical trials using autologous (self-donated) bone marrow mononuclear cells (BMMCs) demonstrated excellent safety, but only modest efficacy. Challenges with autologous stem cells include reduced quality and efficacy with increased patient age. The use of allogeneic mesenchymal precursor cells (MPCs) offers an "off the shelf" therapy, with consistent potency and less variability than autologous cells. AREAS COVERED: Preclinical and initial clinical trials with allogeneic MPCs have been encouraging, providing the support for a large ongoing Phase III trial-DREAM-HF. We provide a comprehensive review of preclinical and clinical data supporting MPCs as a therapeutic option for HF patients. EXPERT OPINION: The current data suggest allogeneic MPCs are a promising therapy for HF patients. The results of DREAM-HF will determine whether allogeneic MPCs can decrease major adverse clinical events (MACE) in advanced HF patients. PMID- 27376189 TI - Treatment of muscle weakness in neuromuscular disorders. AB - INTRODUCTION: Weakness is one of the predominant clinical manifestations of neuromuscular disorders (NMDs), which strongly influences daily life, prognosis, and outcome of affected patients. One of the major therapeutic goals in NMD patients is to completely resolve muscle weakness. Various treatment options are available and include physical therapy, electrotherapy, diet, drugs, avoidance or withdrawal of muscle-toxic and weakness-inducing agents, detoxification, stem cell-therapy, plasma-exchange, respiratory therapy, or surgery. Most accessible to treatment is weakness from immune-mediated neuropathies, immune-mediated transmission-disorders, and idiopathic immune myopathies. Areas covered: This manuscript aims to summarize and discuss recent findings and future perspectives concerning the treatment of muscle weakness in NMDs. Data were obtained by a literature search in databases such as PubMed and Current-Contents. Expert commentary: Weakness is most easily treatable in acquired NMDs and in hereditary myopathies and neuropathies beneficial treatment options are also available. Research needs to be encouraged and intensified to further expand the spectrum of treatment options for weakness. PMID- 27376190 TI - Foundations of heavy-fermion superconductivity: lattice Kondo effect and Mott physics. AB - This article overviews the development of heavy-fermion superconductivity, notably in such rare-earth-based intermetallic compounds which behave as Kondo lattice systems. Heavy-fermion superconductivity is of unconventional nature in the sense that it is not mediated by electron-phonon coupling. Rather, in most cases the attractive interaction between charge carriers is apparently magnetic in origin. Fluctuations associated with an antiferromagnetic (AF) quantum critical point (QCP) play a major role. The first heavy-fermion superconductor CeCu2Si2 turned out to be the prototype of a larger group of materials for which the underlying, often pressure-induced, AF QCP is likely to be of a three dimensional (3D) spin-density-wave (SDW) variety. For UBe13, the second heavy fermion superconductor, a magnetic-field-induced 3D SDW QCP inside the superconducting phase can be conjectured. Such a 'conventional', itinerant QCP can be well understood within Landau's paradigm of order-parameter fluctuations. In contrast, the low-temperature normal-state properties of a few heavy-fermion superconductors are at odds with the Landau framework. They are characterized by an 'unconventional', local QCP which may be considered a zero-temperature 4 f orbital selective Mott transition. Here, as concluded for YbRh2Si2, the breakdown of the Kondo effect concurring with the AF instability gives rise to an abrupt change of the Fermi surface. Very recently, superconductivity was discovered for this compound at ultra-low temperatures. Therefore, YbRh2Si2 along with CeRhIn5 under pressure provide a natural link between the large group of about fifty low temperature heavy-fermion superconductors and other families of unconventional superconductors with substantially higher T c, e.g. the doped Mott insulators of the perovskite-type cuprates and the organic charge-transfer salts. PMID- 27376191 TI - A sensitive sandwich-type electrochemical aptasensor for thrombin detection based on platinum nanoparticles decorated carbon nanocages as signal labels. AB - In this work, a novel and sensitive sandwich-type electrochemical aptasensor has been developed for thrombin detection based on platinum nanoparticles (Pt NPs) decorated carbon nanocages (CNCs) as signal tags. The morphological and compositional of the Pt NPs/CNCs were examined using transmission electron microscopy, X-ray diffraction, and Raman spectroscopy. The results showed that the Pt NPs with about 3-5nm in diameter were well dispersed on the surface of CNCs. The thiolated aptamer was firstly immobilized on the gold electrode to capture the thrombin molecules, and then aptamer functionalized Pt NPs/CNCs nanocomposites were used to fabricate a sandwich sensing platform. Then, the high content Pt NPs on carbon nanocages acting as hydrogen peroxide-mimicking enzyme catalyzed the reduction of H2O2, resulting in significant electrochemical signal amplification. Differential pulse voltammetry is employed to detect thrombin with different concentrations. Under optimized conditions, the approach provided a good linear response range from 0.05 pM to 20nM with a low detection limit of 10fM. This Pt NPs/CNCs-based aptasensor shows good precision, acceptable stability and reproducibility, which provided a promising strategy for electrochemical aptamer-based detection of other biomolecules. PMID- 27376192 TI - A one-pot strategy for the detection of proteins based on sterically and allosterically tunable hybridization chain reaction. AB - In this work, we report a facile one-pot strategy for protein detection based on sterically and allosterically tunable hybridization chain reaction (HCR). In our strategy, DNA hairpins H1 and H2 are dual-labeled with pyrene moieties through a six-carbon-atom spacer at each end; and a single-stranded DNA primer is designed to contain two small molecules near each end. In the absence of target protein, the primer can trigger HCR events between alternating H1 and H2 hairpins to form a nicked double-helix. As a result, the pyrene excimers are formed to emit at approximately 485nm. On the contrary, upon binding of the specific target protein onto the primer through the protein-small molecule interaction, the HCR will be inhibited due to the steric and allosteric effect. The changes of the fluorescent signals of pyrene excimers are in response to the concentration of target protein, so that the detection of protein can be realized. We have demonstrated the feasibility of this strategy by using streptavidin (SA) and folate receptor (FR) as model targets. Results show that both of them can be well detected with a detection limit of 1.07nM and 2.7nM, respectively. The developed method for protein assay is flexible, so we infer that the one-pot strategy holds great potential for the detection of other proteins. PMID- 27376193 TI - 8-hydroxy-2'-deoxyguanosine (8-OHdG) biomarker detection down to picoMolar level on a plastic antibody film. AB - An innovative biosensor assembly relying on a simple and straightforward in-situ construction is presented to monitor urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) down to the pmol/L level. The sensing film of the biosensor consisted of a molecularly imprinted polymer (MIP) layer for 8-OHdG assembled on a gold electrode through electropolymerization of monomer combined with the template. The analytical features of the resulting biosensor were assessed by Cyclic Voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS). Some experimental parameters such as the initial concentration of the monomer and the ratio template-monomer were investigated and optimized in order to finely tune the performance of the MIP-based sensor. Under optimal conditions, the developed biosensor was able to rebind 8-OHdG with a linear response against EIS from 0.1 to 100pg/ml 3.5-3500 pM. The interference of coexisting species was tested, also with calibrations on urine samples, and good selectivity towards 8-OHdG was obtained. RAMAN spectroscopy, FTIR and SEM evaluations of the prepared films confirmed the formation of a polyphenol thin-film on the electrode surface. The presence and distribution of the imprinted cavities on the MIP layer was confirmed by confocal microscopy imaging of the film, after a post-treatment with Fluorescein Isothiocyanate (FITC) labeled 8-OHdG antibody. Overall, this label free biosensor for urinary 8-OHdG detection constitutes a promising low-cost alternative to the conventional immunoassay approaches, due to its simplicity, stability, high sensitivity and selectivity for biological sample assays, opening new doors for other applications. PMID- 27376194 TI - Lateral flow based immunobiosensors for detection of food contaminants. AB - Safety of food is of great concern these days due to various contaminations including toxins, infectious agents and chemical contaminants. Therefore, there is a need to develop promising and user's friendly method to monitor food safety. Lateral flow tests are new, simple and rapid alternative for detection of food borne pathogens compared with traditional methods. In this review article, we surveyed application of lateral flow biosensors in detection of different food contaminants and labels used to enhance the efficiency of the system. Finally, the unique feature of multi-parametric analysis of analytes by lateral flow device has been reported, proving a lateral flow system is able to be designed in a way to detect multiple targets, simultaneously. PMID- 27376195 TI - Integrated microfluidic device using a single universal aptamer to detect multiple types of influenza viruses. AB - DNA aptamers that can bind specific molecular targets have great potential as probes for microbial diagnostic applications. However, aptamers may change their conformation under different operating conditions, thus affecting their affinity and specificity towards the target molecules. In this study, a new integrated microfluidic system was developed that exploited the predictable change in conformation of a single universal influenza aptamer exposed to differing ion concentrations in order to detect multiple types of the influenza virus. Furthermore, the fluorescent-labeled universal aptamer used in this system could distinguish and detect three different influenza viruses (influenza A H1N1, H3N2, and influenza B) at the same time in 20min and therefore has great potential for point-of-care applications requiring rapid diagnosis of influenza viruses. PMID- 27376196 TI - An immunoassay-based reverse-transcription loop-mediated isothermal amplification assay for the rapid detection of avian influenza H5N1 virus viremia. AB - Avian influenza virus (AIV) subtype H5N1 attracts particular consideration because it is a continuous threat to animals and public health systems. The viremia caused by AIV H5N1 infection may increase the risk of blood-borne transmission between humans. Therefore, there is a need to rapidly evaluate and implement screening measures for AIV H5N1 viremia that allows for rapid response to this potentially pandemic threat. The present report describes an immunoassay based reverse-transcription loop-mediated isothermal amplification (immuno-RT LAMP) assay for the rapid detection of AIV H5N1 in whole blood samples. Using PCR tubes coated with an H5 subtype monoclonal antibody, AIV H5N1 virions were specifically captured from blood samples. After a thermal lysis step, the released viral N1 gene was exponentially amplified using RT-LAMP on either a real time PCR instrument for quantitative analysis, or in a water bath system for endpoint analysis. The detection limit of the newly developed immuno-RT-LAMP assay was as low as 1.62*10(1) 50% embryo infectious dose/mL of virus in both regular samples and simulated viremia samples. There were no cross-reactions with non-H5N1 influenza viruses or other avian viruses. The reproducibility of the assay was confirmed using intra- and inter-assay tests with variability ranging from 1.05% to 3.37%. Our results indicate that immuno-RT-LAMP is a novel, effective point-of-care virus identification solution for the rapid diagnosis and monitoring of AIV H5N1 in blood samples. PMID- 27376197 TI - Impact of CCL2 and CCR2 chemokine/receptor deficiencies on macrophage recruitment and continuous glucose monitoring in vivo. AB - The accumulation of macrophages (MPhi) at the sensor-tissue interface is thought to be a major player in controlling tissue reactions and sensor performance in vivo. Nevertheless until recently no direct demonstration of the causal relationship between MPhi aggregation and loss of sensor function existed. Using a Continuous Glucose Monitoring (CGM) murine model we previously demonstrated that genetic deficiencies of MPhi or depletion of MPhi decreased MPhi accumulation at sensor implantation sites, which led to significantly enhanced CGM performance, when compared to normal mice. Additional studies in our laboratories have also demonstrated that MPhi can act as "metabolic sinks" by depleting glucose levels at the implanted sensors in vitro and in vivo. In the present study we extended these observations by demonstrating that MPhi chemokine (CCL2) and receptor (CCR2) knockout mice displayed a decrease in inflammation and MPhi recruitment at sensor implantation sites, when compared to normal mice. This decreased MPhi recruitment significantly enhanced CGM performance when compared to control mice. These studies demonstrated the importance of the CCL2 family of chemokines and related receptors in MPhi recruitment and sensor performance and suggest chemokine targets for enhancing CGM in vivo. PMID- 27376198 TI - Facile synthesis of red emitting 3-aminophenylboronic acid functionalized copper nanoclusters for rapid, selective and highly sensitive detection of glycoproteins. AB - As an emerging class of fluorescent probes, copper nanoclusters (Cu NCs) have been considered as an intriguing candidate for detecting biomoleculars due to their outstanding fluorescent properties, excellent biocompatibility and low cost. Herein, we fabricated bovine serum albumin (BSA) protected Cu NCs (BSA-Cu NCs) and further functionalized them with 3-aminophenylboronic acid (APBA) for selectively discerning glycoproteins. In aqueous solution, Cu(2+) ions were directly reduced into BSA-Cu NCs by hydrazine hydrate (N2H4.H2O) at room temperature using BSA as the capping agent. The synthetic process was very rapid, simple and easy for controlling due to the lack of any other complicated procedure such as heating and adjusting the pH value of the reactive mixture. The APBA-Cu NCs showed strong fluorescent emission at 630nm in the red range. So it can effectively avoid the disturbance of auto-fluorescence in biosamples. The fluorescence of the APBA-Cu NCs was obviously quenched by glycoprotein samples. Then, the APBA-Cu NCs were employed as a probe for selective capture and sensitive detection of glycoproteins with a wide linear range of 5-220nM and a low detection limit of 2.60nM owing to the covalent reaction between the boric acid group of APBA and the cis-glycol groups of the glycoproteins. The developed method was also successfully applied to determine glycoproteins in egg white of chickens and human urine samples with quantitative spike recoveries from 95% to 104%. PMID- 27376199 TI - Products derived from olive leaves and fruits can alter in vitro ruminal fermentation and methane production. AB - BACKGROUND: The industrial processing of olive generates a high quantity of by products. The objective of this study was to examine the effects of products derived from olive trees, i.e. leaves, fruits or kernels as a sole substrate (part A), and crude extract from leaves combined with a substrate (part B) on rumen microbial fermentation in an in vitro batch fermentation system. In this study, total gas production, methane production, and concentrations of volatile fatty acids (VFA) and ammonia in ruminal fluid were measured. RESULTS: In part A, in vitro fermentation of leaves or fruits yielded a gas and total VFA production that were comparable with control substrate, while most of them produced significantly less methane (up to 55.6%) when compared to control substrate. In part B, amongst leaf extracts, only addition of chloroform extract reduced methane production, which was also associated with a decrease (P < 0.01) in gas production. This effect was associated with a significant reduction (P < 0.01) in acetate to propionate ratio and ammonia production, but not in reduction in VFA concentrations. CONCLUSION: Olive leaf and olive leaf chloroform extract reduced ammonia production and increased the molar proportion of propionate in the rumen and can assist in developing novel feed additives for methane mitigation from the rumen. (c) 2016 Society of Chemical Industry. PMID- 27376201 TI - Improved selectivity of mIBG uptake into neuroblastoma cells in vitro and in vivo by inhibition of organic cation transporter 3 uptake using clinically approved corticosteroids. AB - INTRODUCTION: Radiolabeled meta-iodobenzylguanidine (mIBG) is used for imaging and therapy of neuroblastoma as well as pheochromocytoma. However, non-tumorous tissues also incorporate mIBG mainly by organic cation transporters (OCTs). In this study, we tested different clinically approved corticosteroids as potential inhibitors of the OCT3-mediated uptake in vitro and in vivo, to achieve a more selective mIBG tumor uptake. METHODS: The in vitro incorporation of [(3)H]norepinephrine ([(3)H]NE), [(3)H]dopamine ([(3)H]DA) and [(123)I]mIBG in neuroblastoma cells (SK-N-SH, Kelly, IMR-32) and in HEK-293 cells transfected with human OCT3 was measured with and without supplemental corticosteroids (hydrocortisone, prednisolone, dexamethasone, corticosterone). The in vivo biodistribution of [(123)I]mIBG in absence and presence of corticosteroids was studied in non-tumor bearing NOD scid gamma mice. Retrospectively, we selected patients with and without corticosteroid treatment prior to [(123)I]mIBG scintigraphy. RESULTS: A concentration-dependent inhibitory effect of different corticosteroids on the [(3)H]NE and [(3)H]DA uptake via OCT3 was illustrated in vitro. The highest OCT3 inhibition was observed for corticosterone, but clinically used corticosteroids, showed also promising inhibitory effects. In contrast, the uptake in neuroblastoma cells was reduced only moderately. Hydrocortisone or prednisolone had only minor effects on [(123)I]mIBG uptake of both neuroblastoma cells, but reduced uptake in OCT3 expressing cells significantly. In mice tissues, [(123)I]mIBG uptake was inhibited by corticosteroids especially in the small intestine and kidney. Finally, in one patient with hydrocortisone treatment performed prior to [(123)I]mIBG scan, heart and liver uptake was reduced compared to untreated patients. CONCLUSIONS: The OCT3 is widely spread in many organs and responsible for non-targeted uptake of radiolabeled mIBG. In our study, clinically approved corticosteroids inhibited mIBG uptake in OCT3 expressing cells effectively, whereas tracer accumulation in NT (norepinephrine transporter) expressing neuroblastoma cells showed consistency. We conclude, that a single dose of hydrocortisone or prednisolone prior to [(123)I]mIBG scintigraphy may improve specificity and reduce radiation dose to non-target organs. PMID- 27376202 TI - The role of SLAMF7 in multiple myeloma: impact on therapy. AB - INTRODUCTION: Multiple myeloma (MM), a mature B-cell neoplasm, is the second most common hematologic malignancy worldwide. Despite significant improvements in outcome with new therapies, the majority of responding patients will eventually develop resistance to treatment. Furthermore, patients swith disease refractory to both proteasome inhibitors and immunomodulatory drugs (IMiDs) have a poor prognosis. Areas covered: Several new therapeutic approaches are emerging and immunotherapeutic strategies present an important advance for the treatment of patients with relapsed or refractory MM. Among the monoclonal antibodies under development in MM, those targeting SLAMF7 and CD38 have shown the most consistent benefit in trials to date. In this review, we will specifically focus on elotuzumab (anti-SLAMF7 antibody), and provide a summary of the mechanism of action, the clinical results and the safety profile of this new drug. Expert commentary: Although elotuzumab has no single agent activity in MM, randomized trials in relapsed/refractory MM have demonstrated significantly improved progression-free survival when the agent is added to bortezomib-dexamethasone or lenalidomide-dexamethasone. Furthermore, this agent with its novel mechanism of action can be combined with standard therapies without a significant increase in toxicity. Elotuzumab is a highly effective therapy and future data are necessary to identify the best place for this therapy in the setting of MM. PMID- 27376203 TI - Case Reports. PMID- 27376204 TI - Acute Appendicitis Complicating into Portal and Superior Mesenteric Vein Thrombosis. AB - This case report describes a young man who presented with 9-day history of sudden onset epigastric and right-sided lower abdominal pain. He was tachycardiac with temperature of 102 degrees F. Tenderness was present in the peri-umbilical area and right iliac fossa. Investigations revealed a raised total leucocyte count (predominantly neutrophilic). Triphasic CTscan abdomen found thrombosis of right portal vein and its hepatic tributaries alongwith superior mesenteric vein (SMV) and its tributaries. Co-existent fluid in right hemipelvis abutting the cecum and appendiceal tip was suggestive of acute appendicitis. He was resuscitated with fluids and analgesics and started on intravenous metronidazole and ceftriaxone. Anticoagulation with subcutaneous heparin was commenced and eventually switched over to warfarin. Appendicectomy was not performed as the patient responded to conservative treatment. Appendicitis is associated with multiple complications but secondary venous thrombosis has rarely been reported with it. PMID- 27376206 TI - Pseudomyxoma Retroperitonei: ARare Cause of Retroperitoneal Cystic Mass. AB - Pseudomyxoma retroperitonei is a rare condition, characterized by accumulation of mucinous material in the retroperitoneal space, originating predominantly from the appendiceal mucinous neoplasms. A72-year-old male patient presented with a history of progressive right side abdominal pain for 5 months with a palpable abdominal mass. Ultrasound, computerized tomography, and magnetic resonance imaging showed large right abdominal multiloculated cystic lesion with heterogeneous echoic contents. Colonoscopy revealed normal mucosa with extramural pressure on the right colon and cecum. He underwent complete excision of the mass along with right hemicolectomy. The cystic mass was containing gelatinous material. Histopathology revealed low grade mucinous neoplasm. Pseudomyxoma retroperitonei should be considered in the differential diagnosis of patient presenting with progressive right side abdominal pain and retroperitoneal cystic mass. PMID- 27376205 TI - Successful Parenchyma-Sparing Anatomical Surgery by 3-Dimensional Reconstruction of Hilar Cholangiocarcinoma Combined with Anatomic Variation. AB - The combination of hilar cholangiocarcinoma and anatomic variation constitutes a rare and complicated condition. Precise understanding of 3-dimensional position of tumor in the intrahepatic structure in such cases is important for operation planning and navigation. We report a case of a 61-year woman presenting with hilar cholangiocarcinoma. Anatomic variation and tumor location were well depicted on preoperative multidetector computed tomography (MDCT) combined with 3 dimensional reconstruction as the right posterior segmental duct drained to left hepatic duct. The common hepatic duct, biliary confluence, right anterior segmental duct, and right anterior branch of portal vein were involved by the tumor (Bismuth IIIa). After carefully operation planning, we successfully performed a radical parenchyma-sparing anatomical surgery of hilar cholangiocarcinoma: Liver segmentectomy (segments 5 and 8) and caudate lobectomy. MDCTcombined with 3-dimensional reconstruction is a reliable non-invasive modality for preoperative evaluation of hilar cholangiocarcinoma. PMID- 27376207 TI - Fallopian Tube Herniation through Left Sided Abdominal Drain Site. AB - Intra-abdominal drains have been used since long to prevent intra-abdominal collection, and detect any anastomotic leaks. We report a case of left sided fallopian tube herniation from a left lower abdominal drain site in a 27-year female who underwent caesarian section for breach presentation. Several complications related to drain usage has been described but left sided fallopian tube prolapse through drain site has not been reported in literature. PMID- 27376208 TI - Hyperdominant Left Anterior Descending Artery: ARare Coronary Artery Anomaly. AB - The posterior descending artery supplying the posterior one-third of the inter ventricular septum usually arise from the right coronary artery (RCA) or the left circumflex artery (LCx). Posterior descending artery arising from the left anterior descending artery is a rare anomaly. A66-year man presented with chest pain, ECG changes, and raised biomarkers. A diagnosis of non-STelevation myocardial infarction was made. Coronary angiogram, done on the next day, revealed the posterior descending artery as a continuation of the left anterior descending artery (LAD) beyond the crux and a rudimentary right coronary artery. The left anterior descending artery had subcritical stenosis in proximal course (confirmed on fractional flow reserve) and was advised medical treatment. PMID- 27376209 TI - Complete Impulsive Migration of Feeding Jejunostomy Tube and Jejunal Intussusception - Sporadic Complications of a Common Procedure. AB - Feeding jejunostomy is one of the most widely used procedures for enteral nutrition. It is associated with several complications which can be grouped into mechanical, metabolic, nutritional, and infectious. Amongst mechanical complications, complete impulsive tube migration is rarely seen. We hereby report the case of a 60-year old woman, with advanced esophageal carcinoma, re-admitted in the ward with blocked and stuck Foley's catheter placed in the jejenum for feeding purpose. Within hours of admission, patient developed rapid peristalsis and catheter completely disappeared in the abdomen. Exploratory laparotomy was performed to retrieve the catheter, which revealed jejunal intussception and erosions. Migration of the feeding tube is infrequent complication; however, complete migration is even rarer and needs urgent intervention. PMID- 27376210 TI - Resection-Reconstruction of Aberrant Right Hepatic Artery During Whipple Procedure (Pancreaticoduodenectomy). AB - Aberrant hepatic arterial anatomy poses a challenge for the surgeon during Whipple procedure. Intraoperative injury to the aberrant vasculature results in hemorrhagic or ischemic complications involving the liver and biliary tree. We report a case of replaced right hepatic artery arising from the superior mesenteric artery in a patient with periampullary carcinoma of the pancreas, undergoing pancreaticoduodenectomy. The aberrant artery was found to be coursing through the pancreatic parenchyma. This is a rare vascular anomaly. Resection of the arterial segment and end-to-end anastomosis was fashioned. Intrapancreatic course of the replaced right hepatic artery is a rare anomaly and is best managed by preoperative identification on radiology and meticulous intra-operative dissection and preservation. However, for an intrapancreatic course, resection and reconstruction may occasionally be required. PMID- 27376211 TI - Guide Wire Loss of Femoral Venous Cannulation: Case Report and Literature Review. AB - Placement of a central venous catheter (CVC) is a common procedure, often replaced by femoral vein cannulation. The overall complication rate is 12 - 15%. Loss of a complete guide wire into the circulation is a rare and preventable complication. Here we report a case of guide wire loss during femoral venous cannulation and literature review. PMID- 27376212 TI - Epithelioid Haemangioendothelioma (EHE) of the Liver. AB - A45-year previously known hypertensive lady presented with 2-year history of upper abdominal pain, heaviness, and weight loss. Her radiological assessment suggested the possibility of hepatoma or liver metastases. Considering her age, overall good health and absence of cirrhosis, a liver biopsy was taken which showed hepatic epithelioidhaemangioendothelioma (HEHE), a rare and unusual intermediate grade vascular tumor which can easily be confused with hepatoma or metastatic liver disease. To the best of their knowledge, the authors are most probably reporting the first ever case of HEHE from Pakistan with special emphasis on its clinical presentations, clinico-radiological diagnostic clues, and the management options in the light of the limited retrospective studies. PMID- 27376213 TI - Hepatitis Aand E Co-Infection with Worst Outcome. AB - Infections are still a major problem in the developing countries like Pakistan because of poor sewage disposal and economic restraints. Acute viral hepatitis like Aand E are not uncommon in pediatric age group because of unhygienic food handling and poor sewage disposal, but majority recovers well without any complications. Co-infections are rare occurrences and physicians need to be well aware while managing such conditions to avoid worst outcome. Co-infection with hepatitis Aand E is reported occasionally in the literature, however, other concurrent infections such as hepatitis A with Salmonellaand hepatotropic viruses like viral hepatitis B and C are present in the literature. Co-infections should be kept in consideration when someone presents with atypical symptoms or unusual disease course like this presented case. We report here a girl child who had acute hepatitis A and E concurrent infections and presented with hepatic encephalopathy and had worst outcome, despite all the supportive measures being taken. PMID- 27376215 TI - Urinogenital Myiasis From Blow Fly in a Pakistani Child. AB - Herein is reported the first case of urogenital myiasis from Peshawar, Pakistan. Third instar blow fly larvae were recovered from the urinogenital tract of a 5 year old female child. The larvae were identified as Chrysomya bezziana(Villeneuve), using Light and Scanning Electron microscopic techniques. The study brings into focus the subject of human myiasis, about which little is known in Pakistan. PMID- 27376214 TI - Dengue Fever Presenting Atypically with Viral Conjunctivitis and Subacute Thyroiditis. AB - The majority of dengue viral infections are asymptomatic, though symptoms may range from self-limiting febrile illness to life threatening hemorrhagic manifestations. As the burden of disease is dramatically rising in recent years, more patients with atypical presentations and rare complications are increasingly reported. Dengue virus may rarely involve different organ systems including CNS, liver, and heart. However, involvement of eye and thyroid is extremely rare. We present a case of 32-year old patient who presented with conjunctivitis and subacute thyroiditis and was found to have dengue viral infection as the cause of these conditions. PMID- 27376216 TI - Leishmaniasis with Femoral Bone Involvement. AB - Visceral leishmaniasis is mostly subclinical, but it can become symptomatic and take acute, subacute or chronic forms. Its incubation period varies from weeks to months and can even be as long as years. Avast variety of organ involvement may be there. We report a case of osseous leishmaniasis presenting with only a long standing mild knee pain without any laboratory or organ abnormality and showed a pure bone involvement on X-ray and CTscan. Later on, it developed into a discharging sinus and the discharge showed Leishman bodies which was reconfirmed the rough bite. As the patient had reactions with amphotericin B, systemic glucantine was given which led to clinical improvement and smaller radiological lesion. PMID- 27376217 TI - Intra-cranial Toxoplasmosis in an Immunocompetent Female. AB - Intra-cranial toxoplasmosis is a rare entity occurring mostly in immunosuppressed individuals. It is extremely rare in an immune competent patient. Toxoplasmosis is the third leading cause of food borne illness. Depending upon the site, degree of inflammation and local damage, toxoplasmosis encephalitis and cranial abscess can cause long lasting neurologic sequel. With modern imaging techniques, toxoplasmosis antibody titers, slit lamp examination and brain biopsy, there is improvement in diagnosis along with reduction in the mortality rate. We present a case illustrating the radiological manifestations, complications, potential pitfalls in diagnosis and treatment of intra-cranial toxoplasmosis in immunocompetent patient. PMID- 27376218 TI - Retrograde Percutaneous Coronary Intervention for Left Anterior Descending Chronic Total Occlusion Via an Ipsilateral Intraseptal Collateral Channel Using a Single Guiding Catheter. AB - Successful recanalization of chronic total occlusion (CTO) of coronary arteries has improved symptoms and mortality. In CTO cases, retrograde approach from opposite coronary artery has a better chance of procedural success. But the retrograde approach from opposite site is not always suitable. In certain CTO cases, the distal left anterior descending (LAD) artery is supplied from the intraseptal collateral channel. Controlled antegrade and retrograde tracking (CART) strategy has been developed to improve guidewire crossing and successful recanalization. We report a case of the retrograde percutaneous coronary intervention for the LAD CTO lesion via an ipsilateral intraseptal collateral channel, which was successfully revascularized with reverse CARTtechnique using a single 8-French guiding catheter. PMID- 27376219 TI - Antiphospholipid Antibody Syndrome Presenting with Unilateral Adrenal Hemmorhage. AB - The antiphospholipid antibody syndrome presents with vascular thrombosis which involve both arterial and venous systems. The clinical presentation of antiphospholipid antibody syndrome includes obstetric complications leading to recurrent abortions, presence of circulating antibodies against phospholipids, and multi-organ thromboembolisms. We report a case of a patient who presented with unilateral adrenal hemorrhage and subsequently found to have antiphospholipid antibody syndrome and lupus nephritis. PMID- 27376220 TI - Clinical Overlap of Multiple Sclerosis and Autoimmune Hepatitis: Three Cases. AB - Multiple sclerosis (MS) is an autoimmune, inflammatory disease characterized by demyelination and axonal degeneration in the central nervous system. MS is the second major cause of disability following trauma, and is mostly seen between the ages of 20 - 40 years and in women. Autoimmune hepatitis (AH) is a chronic disease characterized by hypergammaglobulinemia, high levels of transaminases, presence of antibodies, and histologically by the necroinflammatory process with interface hepatitis. In AH, the etiological agent of the disease and the cause of liver injury remain unknown. MS may be associated with AH, autoimmune thyroiditis, and type 1 diabetes mellitus (DM). In literature, 8 cases with overlap of MS and AH have been reported. In this report, we present 3 cases which were detected with overlap of MS and AH, and are very rare condition in literature. PMID- 27376221 TI - Atrial Thrombus in a Premature Newborn Following Cardio-Pulmonary Resuscitation. AB - Critically ill newborns, whether term or preterm, are at great risk for developing symptomatic thromboembolic disease. Comorbidities like inflammation, DIC, fluctuations in cardiac output, congenital heart disease, as well as central venous or arterial catheters, are the predisposing risk factors. Clinically symptomatic or asymptomatic cases are usually picked up by echocardiography, usually done for other indications. Management usually comprises of observation, heparin therapy, thrombo-embolectomy, and catheter directed revascularization. We present a case of premature neonate who developed thrombus at inter-atrial septum as a possible consequence of cardiopulmonary resuscitation, detected by echocardiography. Conversely, there is always a possibility of paradoxical emboli in neonates with patent foramen ovale (PFO). Subsequent clinical course remained asymptomatic and baby was discharged home after 6 weeks with cardiac follow-up. Atrial septal findings of organized clot/thrombus in asymptomatic newborns need to be correlated with the details of neonatal care. Long-term follow-up is dependent on underlying pathology. PMID- 27376222 TI - Torsion of a Term Uterus. AB - Torsion of the pregnant uterus, at term, is a very rare event in obstetric practice. It is associated with high perinatal mortality. We are reporting a case of uterine torsion, where a booked second gravida with previous lower segment cesarean section underwent an emergency cesarean section due to severe lower abdominal pain, persistent fetal tachycardia and poor Bishop Score. Following delivery of baby and placenta, uterus untwisted on itself through 180 degrees and it was realized that the incision had been made on the posterior wall of the uterus. Bilateral tubal ligation (BTL) was done after proper informed consent. This decision was based on unavailability of data on safety of future pregnancies in patients with both anterior and posterior uterine scars. Efforts need to be made to develop consensus for management of these cases, in future. PMID- 27376223 TI - Isolated Uterine Myeloid Sarcoma Preceding the Diagnosis of Acute Myeloid Leukemia. AB - Myeloid sarcoma (MS) is an extramedullary solid tumor composed of leukemic myeloid cells. MS is an uncommon tumor complicating acute myeloid leukemia (AML), or less often myelodysplestic syndrome (MDS) and myeloproliferative disorders. Rarely, MS may precede the systemic onset of AML, which usually follows within months. We report a 36 year-old lady who presented with a cervical-uterine mass, which proved to be MS. Initially, she had no systemic AMLand was treated with hysterectomy and systemic chemotherapy. She developed bilateral-flank pain and renal impairment after 9 months. Imaging revealed a soft-tissue mass in the para aortic and peri-sacral region with bilateral hydronephrosis. Biopsy from the mass confirmed recurrence of MS. Bone marrow (BM) biopsy revealed 20% blasts consistent with AML. She was treated with aggressive chemotherapy and local radiotherapy. Despite these measures, she died of progressive disease. MS should be considered and treated as systemic AML, rather than an isolated mass; and we discuss management issues in such patients. PMID- 27376224 TI - Hemophagocytic Lymphohistiocytosis in an Adult: A Rapidly Progressive Disease with Grave Outcome. AB - Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal syndrome seen primarily in children. It is characterized by pathologic systemic hyper inflammation which in adults is easily overlooked due to non-specific clinical features. Most of the data available are on paedriatic population, making the diagnosis of HLH in adults challenging for the clinician. Here we report a case of HLH in a 48-year male who presented with pyrexia of unknown origin for 2 months but remained undiagnosed despite extensive workup. Due to a high index of suspicion, re-evaluation of bone marrow biopsy was done which showed hemophagocytosis, earlier reported as normal. It led to specific investigations, needed for establishing the diagnostic criteria of HLH. Even though chemotherapy was initiated, the patient did not survive. The aggressive nature of this disease makes it crucial for the physician to be aware of its signs and symptoms for the early diagnosis and immediate introduction of adequate treatment. PMID- 27376225 TI - Glomus Tumor of Trachea in an Adult Male. AB - Glomus tumors most commonly occur in distal extremities, particularly in the subungual region. The origin of these tumors is modified smooth muscle cells of glomus bodies. Trachea is one of the rare sites where normal glomus bodies may be sparse or absent, so occurrence of glomus tumor in trachea is very rare. Only 30 cases have been reported in the literature so far. In this case report, the authors describe a very rare and in fact first case of glomus tumor of trachea in a 45-year male Pakistani patient. PMID- 27376226 TI - Lung Metastasis of Renal Cell Carcinoma: ACase Report of Pulmonary Sarcomatoid Carcinoma. AB - Pulmonary sarcomatoid carcinoma (PSC) is a rare malignant cancer composed of sarcoma and sarcoma-like elements with spindle or giant cell features. We report the case of a 60-year-old male with past medical history of right renal cell carcinoma 2 years earlier. Apulmonary nodule was detected in the left upper lobe, 23 months after nephrectomy. Systemic positron emission tomography-computerized tomography (PET-CT) revealed one high metabolic mass shadow in the left upper lobe. Chest CTscan with contrast revealed a left upper lobe mass (2.9 x 2.5 cm). The case was suspected to be a lung metastasis of renal cell carcinoma. After surgery, the pathology revealed PSC-giant cell carcinoma. The tumor's pathology and treatment methods are discussed. PMID- 27376227 TI - Nasal Pseudotumor in Female. AB - Inflammatory pseudotumor is a solid fibro-inflammatory tumor that clinically mimics a neoplastic lesion. Inflammatory pseudotumor is usually found in the orbits and lungs, but rarely in the sinonasal area. Presence of pseudotumor in nasal cavity is even scarce and there are only a few reports to date. We present a case of pseudotumor involving the nasal tip area in an adult female mimicking as a slowly enlarging mass. PMID- 27376228 TI - Peripheral Primitive Neuroectodermal Tumor of Breast. AB - Peripheral primitive neuroectodermal tumor (PNET) is a malignant tumor of the young, usually found in bony structures. It is extremely rare to find it in the breast. Only 9 cases have been reported in the medical literature. A35-year lady had a painless lump in upper left outer quadrant of her left breast which appeared as a BIRADS III lesion on mammography. However, biopsy and later surgery was done on clinical grounds. Histopathology and immunohistochemistry diagnosed a PNETtumor. It had recurred 8 years after surgery and required chemotherapy. PMID- 27376229 TI - Sympathetic Chain Schwannoma Resembling Carotid Body Tumour. AB - Schwannomas are rare, benign nerve sheath tumours of parapharyngeal space. Differential diagnosis should include salivary gland tumours, paragangliomas, neurofibromas, and metastatic lymph nodes. The tumours may arise from vagus nerve and cervical sympathetic chain (CSC). Diagnosis is usually made by imaging techniques: contrast CT, magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA). Fine needle aspiration cytology (FNAC) is useful diagnostic procedure but poor results are seen in neurogenic tumours. Rarely, a vascular CSC schwannoma at the level of carotid arteries bifurcation may mimic carotid body tumour (CBT) on imaging techniques, especially if they are vascular, causing splaying of internal and external carotid arteries. Clinically patient was asymptomatic except for a pulsatile swelling in neck for 5 years. The presented case resembled CBTclinically, on ultrasound and on imaging techniques causing splaying of carotid arteries. FNAC was inconclusive and was always hemorrhagic. During operation, it was found to be CSC schwannoma just posterior to carotid body. CSC was sacrificed and patient developed Horner syndrome postoperatively. PMID- 27376230 TI - Bomb Blast and Its Consequences: Successful Intensive Care Management of Massive Pulmonary Embolsim. AB - A suicide bomb blast in 2013 at a distant city of Pakistan killed 84 and wounded more than 150 people. Some patients were transferred to our tertiary care hospital because of extreme load on medical services there. This patient arrived at the Aga Khan Hospital, 2 days after the bomb blast injury and underwent an orthopedic procedure. Next day, he developed sudden tachypnea, desaturation, and circulatory collapse. After initial cardiopulmonary resuscitation, he was immediately transferred to surgical intensive care unit. Based on history, echocardiography findings and patient parameters, a clinical diagnosis of massive pulmonary embolism was made and immediate thrombolytic therapy with alteplase was started. The immediate improvement in hemodynamic status was evident following 2 hours of alteplase infusion. This case also highlights the aggressiveness of resuscitation, decision making in initiating thrombolytic therapy on clinical grounds, importance of deep venous thrombosis prophylaxis, and exhaustion of health resources due to blast related mass destruction. PMID- 27376231 TI - Strategies for the Management of Congenital Iris Cysts. AB - Iris cysts can arise from iris pigment epithelium or stroma. We present 3 cases of iris cysts which have been managed in different ways. In a one-month neonate, cyst was punctured with keratome and gentle diode laser endophotocoagulation was applied to the base. A2.5-month infant presented with watering and blepharospasm since birth. Clear fluid was aspirated from the cyst with a 27-gauge needle and Ethanol 96% (ETOH) was injected into the cyst and then aspirated. It was followed by injection/aspiration of 0.3 ml of balanced salt solution thrice. Cyst wall was excised. A13-month toddler presented with 4-month history of intermittent irritation and photophobia. The cyst was aspirated with a 25-gauge needle and the cyst walls were nibbled with 20-gauge vitrectomy cutter. Excision is better than injection of sclerosing solutions. The aim is to remove the whole cyst to avoid recurrence and to prevent amblyopia. PMID- 27376232 TI - Appendicitis in an Infant with Atypical Features. AB - Acute appendicitis is an uncommon and challenging disease in infancy. Usually, the clinical presentation in neonates and infants is non-specific and varies depending on the age of the child and duration of the disease. Diagnosis of incomplete and atypical Kawasaki disease (KD) in infants is also a challenging aspect and there is no gold standard for this diagnosis and sometimes fever is the only symptom that could be found. Herein, we report a 6-month infant with a 7 days of fever and bilateral pleural effusion, elevated erythrocyte sedimentation rate, thrombocytosis, hypo-albominemia, normal abdominal ultrasound, and primary diagnosis of KD. Final diagnosis was perforated retrocecal appendicitis and abscess formation. Physicians should be aware of the vague signs and symptoms of acute appendicitis in neonates and infants and consider this diagnosis to prevent delayed diagnosis, inappropriate treatment, and consequent morbidity and mortality. PMID- 27376233 TI - An Unusual Presentation of Opioid Induced Cerebral Infarction. AB - Opioid induced cerebral infarction is one of the most dreadful complications encountered in clinical practice. A30-year known hypertensive male presented to the emergency department of Shalamar Hospital, Lahore, Pakistan, with altered state of consciousness. He had been in his usual state of health a day before the presentation. On examination he was afebrile, his GCS was 3/15 having pinpoint pupils with absent doll's eye movements. His blood pressure was 90/60 mmHg, pulse rate was 62/minute, and respiratory rate was 10/minute. His right plantar was upgoing. He was resuscitated in emergency and was placed on ventilator due to hypoxemia. Computed tomography (CT) of brain revealed bilateral internal capsule hypolucencies and bilateral frontal lobe infarction. His urinary toxicological screening revealed extremely high concentrations of opioids and benzodiazepine. Patient made an uneventful recovery with antidote and supportive care. PMID- 27376234 TI - Perilipin 5 is protective in the ischemic heart. AB - BACKGROUND: Myocardial ischemia is associated with alterations in cardiac metabolism, resulting in decreased fatty acid oxidation and increased lipid accumulation. Here we investigate how myocardial lipid content and dynamics affect the function of the ischemic heart, and focus on the role of the lipid droplet protein perilipin 5 (Plin5) in the pathophysiology of myocardial ischemia. METHODS AND RESULTS: We generated Plin5(-/-) mice and found that Plin5 deficiency dramatically reduced the triglyceride content in the heart. Under normal conditions, Plin5(-/-) mice maintained a close to normal heart function by decreasing fatty acid uptake and increasing glucose uptake, thus preserving the energy balance. However, during stress or myocardial ischemia, Plin5 deficiency resulted in myocardial reduced substrate availability, severely reduced heart function and increased mortality. Importantly, analysis of a human cohort with suspected coronary artery disease showed that a common noncoding polymorphism, rs884164, decreases the cardiac expression of PLIN5 and is associated with reduced heart function following myocardial ischemia, indicating a role for Plin5 in cardiac dysfunction. CONCLUSION: Our findings indicate that Plin5 deficiency alters cardiac lipid metabolism and associates with reduced survival following myocardial ischemia, suggesting that Plin5 plays a beneficial role in the heart following ischemia. PMID- 27376235 TI - Genetic dissection of the alpha-globin super-enhancer in vivo. AB - Many genes determining cell identity are regulated by clusters of Mediator-bound enhancer elements collectively referred to as super-enhancers. These super enhancers have been proposed to manifest higher-order properties important in development and disease. Here we report a comprehensive functional dissection of one of the strongest putative super-enhancers in erythroid cells. By generating a series of mouse models, deleting each of the five regulatory elements of the alpha-globin super-enhancer individually and in informative combinations, we demonstrate that each constituent enhancer seems to act independently and in an additive fashion with respect to hematological phenotype, gene expression, chromatin structure and chromosome conformation, without clear evidence of synergistic or higher-order effects. Our study highlights the importance of functional genetic analyses for the identification of new concepts in transcriptional regulation. PMID- 27376236 TI - Rapid genotype imputation from sequence without reference panels. AB - Inexpensive genotyping methods are essential for genetic studies requiring large sample sizes. In human studies, array-based microarrays and high-density haplotype reference panels allow efficient genotype imputation for this purpose. However, these resources are typically unavailable in non-human settings. Here we describe a method (STITCH) for imputation based only on sequencing read data, without requiring additional reference panels or array data. We demonstrate its applicability even in settings of extremely low sequencing coverage, by accurately imputing 5.7 million SNPs at a mean r(2) value of 0.98 in 2,073 outbred laboratory mice (0.15* sequencing coverage). In a sample of 11,670 Han Chinese (1.7* coverage), we achieve accuracy similar to that of alternative approaches that require a reference panel, demonstrating that our approach can work for genetically diverse populations. Our method enables straightforward progression from low-coverage sequence to imputed genotypes, overcoming barriers that at present restrict the application of genome-wide association study technology outside humans. PMID- 27376237 TI - Genome-wide association study of behavioral, physiological and gene expression traits in outbred CFW mice. AB - Although mice are the most widely used mammalian model organism, genetic studies have suffered from limited mapping resolution due to extensive linkage disequilibrium (LD) that is characteristic of crosses among inbred strains. Carworth Farms White (CFW) mice are a commercially available outbred mouse population that exhibit rapid LD decay in comparison to other available mouse populations. We performed a genome-wide association study (GWAS) of behavioral, physiological and gene expression phenotypes using 1,200 male CFW mice. We used genotyping by sequencing (GBS) to obtain genotypes at 92,734 SNPs. We also measured gene expression using RNA sequencing in three brain regions. Our study identified numerous behavioral, physiological and expression quantitative trait loci (QTLs). We integrated the behavioral QTL and eQTL results to implicate specific genes, including Azi2 in sensitivity to methamphetamine and Zmynd11 in anxiety-like behavior. The combination of CFW mice, GBS and RNA sequencing constitutes a powerful approach to GWAS in mice. PMID- 27376239 TI - Hierarchy within the mammary STAT5-driven Wap super-enhancer. AB - Super-enhancers comprise dense transcription factor platforms highly enriched for active chromatin marks. A paucity of functional data led us to investigate the role of super-enhancers in the mammary gland, an organ characterized by exceptional gene regulatory dynamics during pregnancy. ChIP-seq analysis for the master regulator STAT5A, the glucocorticoid receptor, H3K27ac and MED1 identified 440 mammary-specific super-enhancers, half of which were associated with genes activated during pregnancy. We interrogated the Wap super-enhancer, generating mice carrying mutations in STAT5-binding sites within its constituent enhancers. Individually, the most distal site displayed the greatest enhancer activity. However, combinatorial mutation analysis showed that the 1,000-fold induction in gene expression during pregnancy relied on all enhancers. Disabling the binding sites of STAT5, NFIB and ELF5 in the proximal enhancer incapacitated the entire super-enhancer. Altogether, these data suggest a temporal and functional enhancer hierarchy. The identification of mammary-specific super-enhancers and the mechanistic exploration of the Wap locus provide insights into the regulation of cell-type-specific expression of hormone-sensing genes. PMID- 27376240 TI - Nonlinear multiscale regularisation in MR elastography: Towards fine feature mapping. AB - : Fine-featured elastograms may provide additional information of radiological interest in the context of in vivo elastography. Here a new image processing pipeline called ESP (Elastography Software Pipeline) is developed to create Magnetic Resonance Elastography (MRE) maps of viscoelastic parameters (complex modulus magnitude |G*| and loss angle phi) that preserve fine-scale information through nonlinear, multi-scale extensions of typical MRE post-processing techniques. METHODS: A new MRE image processing pipeline was developed that incorporates wavelet-domain denoising, image-driven noise estimation, and feature detection. ESP was first validated using simulated data, including viscoelastic Finite Element Method (FEM) simulations, at multiple noise levels. ESP images were compared with MDEV pipeline images, both in the FEM models and in three ten subject cohorts of brain, thigh, and liver acquisitions. ESP and MDEV mean values were compared to 2D local frequency estimation (LFE) mean values for the same cohorts as a benchmark. Finally, the proportion of spectral energy at fine frequencies was quantified using the Reduced Energy Ratio (RER) for both ESP and MDEV. RESULTS: Blind estimates of added noise (sigma) were within 5.3% +/- 2.6% of prescribed, and the same technique estimated sigma in the in vivo cohorts at 1.7 +/- 0.8%. A 5 * 5 * 5 truncated Gabor filter bank effectively detects local spatial frequencies at wavelengths lambda <= 10px. For FEM inversions, mean |G*| of hard target, soft target, and background remained within 8% of prescribed up to sigma=20%, and mean phi results were within 10%, excepting hard target phi, which required redrawing around a ring artefact to achieve similar accuracy. Inspection of FEM |G*| images showed some spatial distortion around hard target boundaries and inspection of phi images showed ring artefacts around the same target. For the in vivo cohorts, ESP results showed mean correlation of R=0.83 with MDEV and liver stiffness estimates within 7% of 2D-LFE results. Finally, ESP showed statistically significant increase in fine feature spectral energy as measured with RER for both |G*| (p<1*10-9) and phi (p<1*10-3). CONCLUSION: Information at finer frequencies can be recovered in ESP elastograms in typical experimental conditions, however scatter- and boundary-related artefacts may cause the fine features to have inaccurate values. In in vivo cohorts, ESP delivers an increase in fine feature spectral energy, and better performance with longer wavelengths, than MDEV while showing similar stability and robustness. PMID- 27376238 TI - Genome-wide association of multiple complex traits in outbred mice by ultra-low coverage sequencing. AB - Two bottlenecks impeding the genetic analysis of complex traits in rodents are access to mapping populations able to deliver gene-level mapping resolution and the need for population-specific genotyping arrays and haplotype reference panels. Here we combine low-coverage (0.15*) sequencing with a new method to impute the ancestral haplotype space in 1,887 commercially available outbred mice. We mapped 156 unique quantitative trait loci for 92 phenotypes at a 5% false discovery rate. Gene-level mapping resolution was achieved at about one fifth of the loci, implicating Unc13c and Pgc1a at loci for the quality of sleep, Adarb2 for home cage activity, Rtkn2 for intensity of reaction to startle, Bmp2 for wound healing, Il15 and Id2 for several T cell measures and Prkca for bone mineral content. These findings have implications for diverse areas of mammalian biology and demonstrate how genome-wide association studies can be extended via low-coverage sequencing to species with highly recombinant outbred populations. PMID- 27376241 TI - Emerging Targets in Photopharmacology. AB - The field of photopharmacology uses molecular photoswitches to establish control over the action of bioactive molecules. It aims to reduce systemic drug toxicity and the emergence of resistance, while achieving unprecedented precision in treatment. By using small molecules, photopharmacology provides a viable alternative to optogenetics. We present here a critical overview of the different pharmacological targets in various organs and a survey of organ systems in the human body that can be addressed in a non-invasive manner. We discuss the prospects for the selective delivery of light to these organs and the specific requirements for light-activatable drugs. We also aim to illustrate the druggability of medicinal targets with recent findings and emphasize where conceptually new approaches have to be explored to provide photopharmacology with future opportunities to bring "smart" molecular design ultimately to the realm of clinical use. PMID- 27376242 TI - Instantaneous ballistic velocity of suspended Brownian nanocrystals measured by upconversion nanothermometry. AB - Brownian motion is one of the most fascinating phenomena in nature. Its conceptual implications have a profound impact in almost every field of science and even economics, from dissipative processes in thermodynamic systems, gene therapy in biomedical research, artificial motors and galaxy formation to the behaviour of stock prices. However, despite extensive experimental investigations, the basic microscopic knowledge of prototypical systems such as colloidal particles in a fluid is still far from being complete. This is particularly the case for the measurement of the particles' instantaneous velocities, elusive due to the rapid random movements on extremely short timescales. Here, we report the measurement of the instantaneous ballistic velocity of Brownian nanocrystals suspended in both aqueous and organic solvents. To achieve this, we develop a technique based on upconversion nanothermometry. We find that the population of excited electronic states in NaYF4:Yb/Er nanocrystals at thermal equilibrium can be used for temperature mapping of the nanofluid with great thermal sensitivity (1.15% K-1 at 296 K) and a high spatial resolution (<1 MUm). A distinct correlation between the heat flux in the nanofluid and the temporal evolution of Er3+ emission allows us to measure the instantaneous velocity of nanocrystals with different sizes and shapes. PMID- 27376243 TI - A charge-density-wave oscillator based on an integrated tantalum disulfide-boron nitride-graphene device operating at room temperature. AB - The charge-density-wave (CDW) phase is a macroscopic quantum state consisting of a periodic modulation of the electronic charge density accompanied by a periodic distortion of the atomic lattice in quasi-1D or layered 2D metallic crystals. Several layered transition metal dichalcogenides, including 1T-TaSe2, 1T-TaS2 and 1T-TiSe2 exhibit unusually high transition temperatures to different CDW symmetry reducing phases. These transitions can be affected by the environmental conditions, film thickness and applied electric bias. However, device applications of these intriguing systems at room temperature or their integration with other 2D materials have not been explored. Here, we demonstrate room temperature current switching driven by a voltage-controlled phase transition between CDW states in films of 1T-TaS2 less than 10 nm thick. We exploit the transition between the nearly commensurate and the incommensurate CDW phases, which has a transition temperature of 350 K and gives an abrupt change in current accompanied by hysteresis. An integrated graphene transistor provides a voltage tunable, matched, low-resistance load enabling precise voltage control of the circuit. The 1T-TaS2 film is capped with hexagonal boron nitride to provide protection from oxidation. The integration of these three disparate 2D materials in a way that exploits the unique properties of each yields a simple, miniaturized, voltage-controlled oscillator suitable for a variety of practical applications. PMID- 27376245 TI - Analysis of single nucleotide polymorphism among Varicella-Zoster Virus and identification of vaccine-specific sites. AB - Varicella-zoster virus (VZV) is a causative agent for chickenpox and zoster. Live attenuated vaccines have been developed based on Oka and MAV/06 strains. In order to understand the molecular mechanisms of attenuation, complete genome sequences of vaccine and wild-type strains were compared and single nucleotide polymorphism (SNP) was analyzed. ORF22 and ORF62 contained the highest number of SNPs. The detailed analysis of the SNPs suggested 24 potential vaccine-specific sites. All the mutational events found in vaccine-specific sites were transitional, and most of them were substitution of AT to GC pair. Interestingly, 18 of the vaccine specific sites of the vaccine strains appeared to be genetically heterogeneous. The probability of a single genome of vaccine strain to contain all 24 vaccine type sequences was calculated to be less than 4%. The average codon adaptation index (CAI) value of the vaccine strains was significantly lower than the CAI value of the clinical strains. PMID- 27376246 TI - Highlights from Faraday Discussion: Chemistry in the urban atmosphere, United Kingdom, April 2016. PMID- 27376244 TI - Optical imaging of individual biomolecules in densely packed clusters. AB - Recent advances in fluorescence super-resolution microscopy have allowed subcellular features and synthetic nanostructures down to 10-20 nm in size to be imaged. However, the direct optical observation of individual molecular targets (~5 nm) in a densely packed biomolecular cluster remains a challenge. Here, we show that such discrete molecular imaging is possible using DNA-PAINT (points accumulation for imaging in nanoscale topography)-a super-resolution fluorescence microscopy technique that exploits programmable transient oligonucleotide hybridization-on synthetic DNA nanostructures. We examined the effects of a high photon count, high blinking statistics and an appropriate blinking duty cycle on imaging quality, and developed a software-based drift correction method that achieves <1 nm residual drift (root mean squared) over hours. This allowed us to image a densely packed triangular lattice pattern with ~5 nm point-to-point distance and to analyse the DNA origami structural offset with angstrom-level precision (2 A) from single-molecule studies. By combining the approach with multiplexed exchange-PAINT imaging, we further demonstrated an optical nanodisplay with 5 * 5 nm pixel size and three distinct colours with <1 nm cross channel registration accuracy. PMID- 27376247 TI - Multifunctional Mesoporous Silica Nanoparticles with Thermal-Responsive Gatekeeper for NIR Light-Triggered Chemo/Photothermal-Therapy. AB - In this work, a matrix metalloproteinase (MMP)-triggered tumor targeted mesoporous silica nanoparticle (MSN) is designed to realize near-infrared (NIR) photothermal-responsive drug release and combined chemo/photothermal tumor therapy. Indocyanine green (ICG) and doxorubicin (DOX) are both loaded in the MSN modified with thermal-cleavable gatekeeper (Azo-CD), which can be decapped by ICG generated hyperthermia under NIR illumination. A peptidic sequence containing a short PEG chain, matrix metalloproteinase (MMP) substrate (PLGVR) and tumor cell targeting motif (RGD) are further decorated on the MSN via a host-guest interaction. The PEG chain can protect the MSN during the circulation and be cleaved off in the tumor tissues with overexpressed MMP, and then the RGD motif is switched on to target tumor cells. After the tumor-triggered targeting process, the NIR irradiation guided by ICG fluorescence can trigger cytosol drug release and realize combined chemo/photothermal therapy. PMID- 27376248 TI - Dimethyl- and monomethylfumarate regulate indoleamine 2,3-dioxygenase (IDO) activity in human immune cells. AB - Fumaric acid esters (FAEs) are used as an oral treatment for psoriasis. Dimethylfumarate (DMF) and its metabolite monomethylfumarate (MMF) are regarded as the pharmacologically active moieties. Indoleamine 2,3-dioxygenase (IDO) is the key enzyme for the metabolism of tryptophan. The kynurenine pathway is established as a major regulator of innate and adaptive immunity. Here, we investigated the effect of DMF and MMF on IDO activity and expression in human peripheral blood mononuclear cells (PBMCs). IDO activity was determined by measuring the concentration of kynurenine in the culture medium using a HPLC technique. IDO and kynureninase protein expressions were analysed by Western blot. Our results demonstrated that DMF and MMF dose-dependently reduced the levels of L-kynurenine in PBMCs activated by interferon-gamma (IFN-gamma). Furthermore, MMF had an inhibitory effect on IDO activity in vitro with an ED50 of 10 MUmol/L, a value within the therapeutic concentration range for this molecule. We also observed that IDO and kynureninase expressions were reduced in PBMCs in a dose-dependent manner by DMF and MMF. The results of our study show that DMF and MMF (in therapeutic concentrations) inhibited IDO and kynureninase activity and expression in a NF-kappaB-dependent manner in PBMCs while also decreasing the level of L-kynurenine in these cells. As we found that FAEs inhibit both IDO expression and enzymatic activity leading to a modulation of tryptophan degradation, we believe this effect may contribute to the clinical efficacy of this drug in psoriasis by downregulating pro-inflammatory mediators generated by the kynurenine pathway. PMID- 27376249 TI - Changes in the microbiota of lamb packaged in a vacuum and in modified atmospheres during chilled storage analysed by high-throughput sequencing. AB - Changes in the microbiota of lamb were investigated under vacuum packaging (VP) and under 20% CO2/80% N2 (LC), 60% CO2/40% N2 (MC), and 100% CO2 (HC) modified atmosphere packaging (MAP) during chilled storage. Viable counts were monitored, and the total microbial communities were assessed by high-throughput sequencing. The starting community had the highest microbial diversity, after which Lactococcus and Carnobacterium spp. outcompeted during the 28-day storage. The relative abundances of Brochothrix spp. in the LC atmosphere were much higher than those of the other groups on days 7 and 28. The bacterial inhibiting effect of the MAP environments on microbial growth was positively correlated with the CO2 concentration. The HC atmosphere inhibited microbial growth and delayed changes in the microbial community composition, extending the lamb's shelf life by approximately 7days compared with the VP atmosphere. Lamb packaged in the VP atmosphere had a more desirable colour but a higher weight loss than lamb packaged in the MAP atmospheres. PMID- 27376250 TI - Relationship between phenotype, carcass characteristics and the incidence of dark cutting in heifers. AB - Previous research has suggested that cattle predisposed to dark cutting can be identified from live animal or carcass characteristics. This hypothesis was tested using production and phenotype data from an existing data set collected from heifers (n=467) on study at three farms. Carcasses in the data set graded Canada AAA (n=136), AA (n=296), A (n=14), and B4 (dark cutting, n=21). Farm was identified as significant (P=0.0268) by CATMOD analysis and slaughter weight and carcass weight accounted for the variation in dark cutting frequency across the farms. Analysis of variance indicated that dark cutting heifers had reduced weight at weaning (P<0.0001) and at slaughter (P<0.0001), and produced reduced weight carcasses (P<0.0001). Results of logistic regression indicated that the probability of dark cutting was decreased in heifers slaughtered at live weight greater than 550kg and in carcasses weighing greater than 325kg. PMID- 27376251 TI - Clinicopathological characteristics of serrated polyps as precursors to colorectal cancer: Current status and management. AB - Serrated polyps have long been thought to lack malignant potential in the human colorectum. However, identification of the serrated pathway to colorectal cancer based on molecular biology has improved our understanding of the pathogenesis of colorectal cancers. Accordingly, serrated polyps such as traditional serrated adenoma and sessile serrated adenoma/polyps (SSA/P) are now considered to be precursor lesions of the serrated pathway. Recently, serrated polyps were classified into three subtypes, consisting of hyperplastic polyp, SSA/P, and traditional serrated adenoma, according to the World Health Organization classification. It has been suggested that SSA/P in the proximal colon are a precursor lesion of pathogenesis of colorectal cancer and are characterized by BRAF mutation and a CpG island methylator phenotype with or without microsatellite instability. However, SSA/P is more challenging to detect by colonoscopy and is likely to account for some interval cancers, particularly in the proximal colon because it presents flat or sessile, isochroous appearance, and occasionally has a mucous cap. Furthermore, the possibility has been raised that pathologists misclassify SSA/P as hyperplastic polyp. It is important for gastroenterologists to recognize the endoscopic features of serrated polyps to facilitate their detection and removal and also to establish postpolypectomy surveillance guidelines. In this review, we discuss the recent classification of serrated polyps; the molecular characteristics of the serrated pathway; appropriate diagnostic methods using endoscopy, including a new image-enhanced endoscopic technique; and management of these lesions. PMID- 27376252 TI - Nucleobase-Functionalized Supramolecular Micelles with Tunable Physical Properties for Efficient Controlled Drug Release. AB - Complementary nucleobase-functionalized polymeric micelles, a combination of adenine-thymine (A-U) base pairs and a blend of hydrophilic-hydrophobic polymer pairs, can be used to construct 3D supramolecular polymer networks; these micelles exhibit excellent self-assembly ability in aqueous solution, rapid pH responsiveness, high drug loading capacity, and triggerable drug release. In this study, a multi-uracil functionalized poly(epsilon-caprolactone) (U-PCL) and adenine end-capped difunctional oligomeric poly(ethylene glycol) (BA-PEG) are successfully developed and show high affinity and specific recognition in solution owing to dynamically reversible A-U-induced formation of physical cross links. The U-PCL/BA-PEG blend system produces supramolecular micelles that can be readily adjusted to provide the desired critical micellization concentration, particle size, and stability. Importantly, in vitro release studies show that doxorubicin (DOX)-loaded micelles exhibit excellent DOX-encapsulated stability under physiological conditions. When the pH value of the solution is reduced from 7.4 to 5.0, DOX-loaded micelles can be rapidly triggered to release encapsulated DOX, suggesting these polymeric micelles represent promising candidate pH responsive nanocarriers for controlled-release drug delivery and pharmaceutical applications. PMID- 27376253 TI - Synthesis and Antimicrobial Activity of 1,2-Benzothiazine Derivatives. AB - A number of 1,2-benzothiazines have been synthesized in a three-step process. Nine chalcones 1-9 bearing methyl, fluoro, chloro and bromo substituents were chlorosulfonated with chlorosulfonic acid to generate the chalcone sulfonyl chlorides 10-18. These were converted to the dibromo compounds 19-27 through reaction with bromine in glacial acetic acid. Compounds 19-27 were reacted with ammonia, methylamine, ethylamine, aniline and benzylamine to generate a library of 45 1,2-benzothiazines 28-72. Compounds 28-72 were evaluated for their antimicrobial activity using broth microdilution techniques against two Gram positive bacteria (Bacillus subtilis and Staphylococcus aureus) and two Gram negative bacteria (Proteus vulgaris and Salmonella typhimurium). The results demonstrated that none of the compounds showed any activity against Gram-negative bacteria P. vulgaris and S. typhimurium; however, compounds 31, 33, 38, 43, 45, 50, 53, 55, 58, 60, 63 and 68 showed activity against Gram-positive bacteria Bacillus subtilis and Staphylococcous aureus. The range of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was 25-600 ug/mL, though some of the MIC and MBC concentrations were high, indicating weak activity. Structure activity relationship studies revealed that the compounds with a hydrogen atom or an ethyl group on the nitrogen of the thiazine ring exerted antibacterial activity against Gram-positive bacteria. The results also showed that the compounds where the benzene ring of the benzoyl moiety contained a methyl group or a chlorine or bromine atom in the para position showed higher antimicrobial activity. Similar influences were identified where either a bromine or chlorine atom was in the meta position. PMID- 27376254 TI - Pingyangmycin and Bleomycin Share the Same Cytotoxicity Pathway. AB - Pingyangmycin is an anticancer drug known as bleomycin A5 (A5), discovered in the Pingyang County of Zhejiang Province of China. Bleomycin (BLM) is a mixture of mainly two compounds (A2 and B2), which is on the World Health Organization's list of essential medicines. Both BLM and A5 are hydrophilic molecules that depend on transporters or endocytosis receptors to get inside of cells. Once inside, the anticancer activities rely on their abilities to produce DNA breaks, thus leading to cell death. Interestingly, the half maximal inhibitory concentration (IC50) of BLMs in different cancer cell lines varies from nM to MUM ranges. Different cellular uptake, DNA repair rate, and/or increased drug detoxification might be some of the reasons; however, the molecules and signaling pathways responsible for these processes are largely unknown. In the current study, we purified the A2 and B2 from the BLM and tested the cytotoxicities and the molecular mechanisms of each individual compound or in combination with six different cell lines, including a Chinese hamster ovary (CHO) cell line defective in glycosaminoglycan biosynthesis. Our data suggested that glycosaminoglycans might be involved in the cellular uptake of BLMs. Moreover, both BLM and A5 shared similar signaling pathways and are involved in cell cycle and apoptosis in different cancer cell lines. PMID- 27376255 TI - A Macrosphelide as the Unexpected Product of a Pleurotus ostreatus Strain Mediated Biotransformation of Halolactones Containing the gem-Dimethylcyclohexane Ring. Part 1. AB - The aim of the study was to obtain new compounds during biotransformation of two halocompounds, the delta-bromo and delta-iodo-gamma-bicyclolactones 1 and 2. Unexpectedly Pleurotus ostreatus produced together with the hydroxylactone, 2 hydroxy-4,4-dimethyl-9-oxabicyclo[4.3.0]nonane-8-one (3), its own metabolite (3S,9S,15S)-(6E,12E)-3,9,15-trimethyl-4,10,16-trioxacyclohexa-deca-6,12-diene 1,5,8,11,14-pentaone (4). The method presented here, in which this macrosphelide 4 was obtained by biotransformation, has not been previously described in the literature. To the best of our knowledge, this compound has been prepared only by chemical synthesis to date. This is the first report on the possibility of the biosynthesis of this compound by the Pleurotus ostreatus strain. The conditions and factors, like temperature, salts, organic solvents, affecting the production of this macrosphelide by Pleurotus ostreatus strain were examined. The highest yield of macroshphelide production was noticed for halolactones, as well with iodide, bromide, iron and copper (2+) ions as inductors. PMID- 27376256 TI - Phenolic Profiles and Antioxidant Activity of Lotus Root Varieties. AB - Lotus root attracts increasing attention mainly because of its phenolic compounds known as natural antioxidants. Its thirteen varieties were systematically analyzed on the content, distribution, composition and antioxidant activity of phenolic compounds for a better understanding of this aquatic vegetable. The respective mean contents of total phenolics in their flesh, peel and nodes were 1.81, 4.30 and 7.35 mg gallic acid equivalents (GAE)/g fresh weight (FW), and those of total flavonoids were 3.35, 7.69 and 15.58 mg rutin equivalents/g FW. The phenolic composition determined by a high-performance liquid chromatography method varied significantly among varieties and parts. The phenolics of flesh were mainly composed of gallocatechin and catechin; those of peel and node were mainly composed of gallocatechin, gallic acid, catechin and epicatechin. The antioxidant activities of phenolic extracts in increasing order were flesh, peel and node; their mean concentrations for 50% inhibition of 2,2-diphenyl-1 picrylhydrazyl radical were 46.00, 26.43 and 21.72 ug GAE/mL, and their mean values representing ferric reducing antioxidant power were 75.91, 87.66 and 100.43 ug Trolox equivalents/100 ug GAE, respectively. "Zoumayang", "Baheou", "No. 5 elian" and "Guixi Fuou" were the hierarchically clustered varieties with relatively higher phenolic content and stronger antioxidant activity as compared with the others. Especially, their nodes and peels are promising sources of antioxidants for human nutrition. PMID- 27376257 TI - Photochemistry of 1,4-Dihydropyridine Derivatives: Diradical Formation, Delocalization and Trapping as a Route to Novel Tricyclic and Tetracyclic Nitrogen Heterocyclic Ring Systems. AB - Irradiation of an acetonitrile solution of 4-aryl-3,5-dibenzoyl-1,4 dihydropyridine derivatives 1a-c and maleimides 2a-c using medium pressure Hg-arc lamp (lambda > 290) nm afforded three different cycloadducts 4, 5, 6 in addition to the oxidation products 3. These results indicate that compounds 1a-c undergoes intermolecular cycloaddition reaction through three biradical intermediates and behave photochemically different than those reported previously for the analogous 3,5-diacetyl and 3,5-dicarboxylic acid derivatives. The present work also offers simple access to novel tricyclic and tetracyclic nitrogen heterocyclic ring systems of potential biological and synthetic applications. The structure of the photoproducts was established spectroscopically and by single crystal X-ray crystallography. PMID- 27376258 TI - Pyridine and p-Nitrophenyl Oxime Esters with Possible Photochemotherapeutic Activity: Synthesis, DNA Photocleavage and DNA Binding Studies. AB - Compared to standard treatments for various diseases, photochemotherapy and photo dynamic therapy are less invasive approaches, in which DNA photocleavers represent promising tools for novel "on demand" chemotherapeutics. A series of p nitrobenzoyl and p-pyridoyl ester conjugated aldoximes, amidoximes and ethanone oximes were subjected to UV irradiation at 312 nm with supercoiled circular plasmid DNA. The compounds which possessed appropriate properties were additionally subjected to UVA irradiation at 365 nm. The ability of most of the compounds to photocleave DNA was high at 312 nm, whereas higher concentrations were required at 365 nm as a result of their lower UV absorption. The affinity of selected compounds to calf-thymus (CT) DNA was studied by UV spectroscopy, viscosity experiments and competitive studies with ethidium bromide (EB) revealing that all compounds interacted with CT DNA. The fluorescence emission spectra of the pre-treated EB-DNA exhibited a moderate to significant quenching in the presence of the compounds indicating the binding of the compounds to CT DNA via intercalation as concluded also by DNA-viscosity experiments. For the oxime esters the DNA photocleavage and affinity studies aimed to clarify the role of the oxime nature (aldoxime, ketoxime, amidoxime) and the role of the pyridine and p-nitrophenyl moieties both as oxime substituents and ester conjugates. PMID- 27376260 TI - Advanced Nanobiomaterials: Vaccines, Diagnosis and Treatment of Infectious Diseases. AB - The use of nanoparticles has contributed to many advances due to their important properties such as, size, shape or biocompatibility. The use of nanotechnology in medicine has great potential, especially in medical microbiology. Promising data show the possibility of shaping immune responses and fighting severe infections using synthetic materials. Different studies have suggested that the addition of synthetic nanoparticles in vaccines and immunotherapy will have a great impact on public health. On the other hand, antibiotic resistance is one of the major concerns worldwide; a recent report of the World Health Organization (WHO) states that antibiotic resistance could cause 300 million deaths by 2050. Nanomedicine offers an innovative tool for combating the high rates of resistance that we are fighting nowadays, by the development of both alternative therapeutic and prophylaxis approaches and also novel diagnosis methods. Early detection of infectious diseases is the key to a successful treatment and the new developed applications based on nanotechnology offer an increased sensibility and efficiency of the diagnosis. The aim of this review is to reveal and discuss the main advances made on the science of nanomaterials for the prevention, diagnosis and treatment of infectious diseases. Highlighting innovative approaches utilized to: (i) increasing the efficiency of vaccines; (ii) obtaining shuttle systems that require lower antibiotic concentrations; (iii) developing coating devices that inhibit microbial colonization and biofilm formation. PMID- 27376259 TI - Study of the UV Light Conversion of Feruloyl Amides from Portulaca oleracea and Their Inhibitory Effect on IL-6-Induced STAT3 Activation. AB - Two new feruloyl amides, N-cis-hibiscusamide (5) and (7'S)-N-cis feruloylnormetanephrine (9), and eight known feruloyl amides were isolated from Portulaca oleracea L. and the geometric conversion of the ten isolated feruloyl amides by UV light was verified. The structures of the feruloyl amides were determined based on spectroscopic data and comparison with literature data. The NMR data revealed that the structures of the isolated compounds showed cis/trans isomerization under normal laboratory light conditions. Therefore, cis and trans isomers of feruloyl amides were evaluated for their convertibility and stability by UV light of a wavelength of 254 nm. After 96 h of UV light exposure, 23.2% 35.0% of the cis and trans-isomers were converted to trans-isomers. Long-term stability tests did not show any significant changes. Among all compounds and conversion mixtures collected, compound 6 exhibited the strongest inhibition of IL-6-induced STAT3 activation in Hep3B cells, with an IC50 value of 0.2 MUM. This study is the first verification of the conversion rates and an equilibrium ratio of feruloyl amides. These results indicate that this natural material might provide useful information for the treatment of various diseases involving IL-6 and STAT3. PMID- 27376261 TI - 18alpha-Glycyrrhetinic Acid Induces Apoptosis of HL-60 Human Leukemia Cells through Caspases- and Mitochondria-Dependent Signaling Pathways. AB - In this study we investigate the molecular mechanisms of caspases and mitochondria in the extrinsic and intrinsic signal apoptosis pathways in human leukemia HL-60 cells after in vitro exposure to 18alpha-glycyrrhetinic acid (18alpha-GA). Cells were exposed to 18alpha-GA at various concentrations for various time periods and were harvested for flow cytometry total viable cell and apoptotic cell death measurements. Cells treated with 18alpha-GA significantly inhibited cell proliferation and induced cell apoptosis in a dose-dependent manner, with an IC50 value of 100 MUM at 48 h. The cell growth inhibition resulted in induction of apoptosis and decreased the mitochondria membrane potential (DeltaPsim) and increased caspase-8, -9 and -3 activities. Furthermore, cytochrome c and AIF were released from mitochondria, as shown by western blotting and confirmed by confocal laser microscopy. Western blotting showed that 18alpha-GA increased the levels of pro-apoptotic proteins such as Bax and Bid and decreased the anti-apoptotic proteins such as Bcl-2 and Bcl-xl, furthermore, results also showed that 18alpha-GA increased Fas and Fas-L which are associated with surface death receptor in HL-60 cells. Based on those observations, the present study supports the hypothesis that 18alpha-GA-induced apoptosis in HL-60 cells involves the activation of the both extrinsic and intrinsic apoptotic pathways. PMID- 27376262 TI - Doping-Promoted Solar Water Oxidation on Hematite Photoanodes. AB - As one of the most promising materials for solar water oxidation, hematite has attracted intense research interest for four decades. Despite their desirable optical band gap, stability and other attractive features, there are great challenges for the implementation of hematite-based photoelectrochemical cells. In particular, the extremely low electron mobility leads to severe energy loss by electron hole recombination. Elemental doping, i.e., replacing lattice iron with foreign atoms, has been shown to be a practical solution. Here we review the significant progresses in metal and non-metal element doping-promoted hematite solar water oxidation, focusing on the role of dopants in adjusting carrier density, charge collection efficiency and surface water oxidation kinetics. The advantages and salient features of the different doping categories are compared and discussed. PMID- 27376263 TI - Assessing and Broadening Genetic Diversity of Elymus sibiricus Germplasm for the Improvement of Seed Shattering. AB - Siberian wild rye (Elymus sibiricus L.) is an important native grass in the Qinghai-Tibet Plateau of China. It is difficult to grow for commercial seed production, since seed shattering causes yield losses during harvest. Assessing the genetic diversity and relationships among germplasm from its primary distribution area contributes to evaluating the potential for its utilization as a gene pool to improve the desired agronomic traits. In the study, 40 EST-SSR primers were used to assess the genetic diversity and population structure of 36 E. sibiricus accessions with variation of seed shattering. A total of 380 bands were generated, with an average of 9.5 bands per primer. The polymorphic information content (PIC) ranged from 0.23 to 0.50. The percentage of polymorphic bands (P) for the species was 87.11%, suggesting a high degree of genetic diversity. Based on population structure analysis, four groups were formed, similar to results of principal coordinate analysis (PCoA). The molecular variance analysis (AMOVA) revealed the majority of genetic variation occurred within geographical regions (83.40%). Two genotypes from Y1005 and ZhN06 were used to generate seven F1 hybrids. The molecular and morphological diversity analysis of F1 population revealed rich genetic variation and high level of seed shattering variation in F1 population, resulting in significant improvement of the genetic base and desired agronomic traits. PMID- 27376264 TI - Enhancement of Exposure and Reduction of Elimination for Paeoniflorin or Albiflorin via Co-Administration with Total Peony Glucosides and Hypoxic Pharmacokinetics Comparison. AB - There is evidence suggesting that herbal extracts demonstrate greater bioactivities than their isolated constituents at an equivalent dose. This phenomenon could be attributed to the absence of interacting substances present in the extracts. By measuring the pharmacokinetic parameters of paeoniflorin (PF) and albiflorin (AF) after being orally administered to rats in isolated form, in combination with each other and within total peony glucosides (TPG), respectively, the current study aimed to identify positive pharmacokinetic interactions between components of peony radix extracts. Moreover, the pharmacokinetic profiles of PF and AF under normoxia and hypoxia were also investigated and compared. In order to achieve these goals, a highly sensitive and reproducible ultra-peformance liquid chromatography-mass spectrometry (UPLC MS) method was developed and validated for simultaneously quantitation of PF and AF in rat plasma. This study found that compared with that of single component (PF/AF), the exposure of PF in rat plasma after combination administration or TPG administration was significantly increased, meanwhile the elimination of PF/AF was remarkably reduced. It was also noticed that AUC and Cmax of PF in hypoxia rats were significantly decreased compared with that of normaxia rats, suggesting that there was a decreased exposure of PF in rats under hypoxia. The current study, for the first time, revealed the pharmacokinetic interactions between PF/AF and other constitutes in TGP and the pharmacokinetic profiles of PF and AF under hypoxia. In view of the current findings, it could be supposed that the clinical performance of total peony glucosides would be better than that of single constitute (PF/AF). The outcomes of this animal study are expected to serve as a basis for development of clinical guidelines on total peony glucosides usage. PMID- 27376265 TI - The Role of p38 MAPK in the Development of Diabetic Cardiomyopathy. AB - Diabetic cardiomyopathy (DCM) is a major complication of diabetes that contributes to an increase in mortality. A number of mechanisms potentially explain the development of DCM including oxidative stress, inflammation and extracellular fibrosis. Mitogen-activated protein kinase (MAPK)-mediated signaling pathways are common among these pathogenic responses. Among the diverse array of kinases, extensive attention has been given to p38 MAPK due to its capacity for promoting or inhibiting the translation of target genes. Growing evidence has indicated that p38 MAPK is aberrantly expressed in the cardiovascular system, including the heart, under both experimental and clinical diabetic conditions and, furthermore, inhibition of p38 MAPK activation in transgenic animal model or with its pharmacologic inhibitor significantly prevents the development of DCM, implicating p38 MAPK as a novel diagnostic indicator and therapeutic target for DCM. This review summarizes our current knowledge base to provide an overview of the impact of p38 MAPK signaling in diabetes-induced cardiac remodeling and dysfunction. PMID- 27376266 TI - Prognostic Value of Affective Symptoms in First-Admission Psychotic Patients. AB - BACKGROUND: Very little research has been conducted in patients with first episode psychosis using a dimensional approach. Affective dimensional representations might be useful to predict the clinical course and treatment needs in such patients. METHODS: Weincluded 112 patients with first-episode psychosis in a longitudinal-prospective study with a five-year follow-up (N = 82). Logistic analyses were performed to determine the predictive factors associated with depressive, manic, activation, and dysphoric dimensions. RESULTS: High scores on the depressive dimension were associated with the best prognosis. On the other hand, high scores on the activation dimension and the manic dimension were associated with a poorer prognosis in terms of relapses. Only the dysphoric dimension was not associated with syndromic or functional prognosis. CONCLUSION: Ourresults suggest that the pattern of baseline affective symptoms helps to predict the course of psychotic illness. Therefore, the systematic assessment of affective symptoms would enable us to draw important conclusions regarding patients' prognosis. Interventions for patients with high scores on manic or activation dimensions could be beneficial in decreasing relapses in first-episode psychosis. PMID- 27376267 TI - Usefulness of Aquaporin 1 as a Prognostic Marker in a Prospective Cohort of Malignant Mesotheliomas. AB - (1) BACKGROUND: Malignant mesothelioma (MM) is an aggressive tumour of the serosal membranes, associated with exposure to asbestos. Survival is generally poor, but prognostication for individual patients is difficult. We recently described Aquaporin 1 (AQP1) as independent prognostic factor in two separate retrospective cohorts of MM patients. Here we assess the usefulness of AQP1 prospectively, and determine the inter-observer agreement in assessing AQP1 scores; (2) METHODS: A total of 104 consecutive cases of MM were included. Sufficient tissue for immunohistochemistry was available for 100 cases, and these cases were labelled for AQP1. Labelling was assessed by two pathologists. Complete clinical information and follow up was available for 91 cases; (3) RESULTS: Labelling of >=50% of tumour cells for AQP indicated improved prognosis in a univariate model (median survival 13 versus 8 months, p = 0.008), but the significance was decreased in a multivariate analysis. Scoring for AQP1 was robust, with an inter-observer kappa value of 0.722, indicating substantial agreement between observers; (4) CONCLUSION: AQP1 is a useful prognostic marker that can be easily incorporated in existing diagnostic immunohistochemical panels and which can be reliably interpreted by different pathologists. PMID- 27376268 TI - PD-L1 Immunohistochemical Detection in Tumor Cells and Tumor Microenvironment: Main Considerations on the Use of Tissue Micro Arrays. AB - PD-1/PD-L1 (programmed death 1/programmed death ligand 1) pathway plays a critical role in immune escape of tumor cells. Recent studies have described that PD-L1 is heterogeneously expressed in various types of cancer, although its prognostic/predictive value is still uncertain. These problems are partly due to a not well defined operating protocol for its detection by immunohistochemistry, but also because most of the studies conducted on large case series were made by Tissue Micro Array (TMA). We are going to discuss this latter point, to highlight that TMA must be set up in an appropriate manner, especially for some markers, such as PD-L1, which, besides being poorly expressed in tumor cells, can be expressed by cells of the tumor microenvironment. PMID- 27376270 TI - The Effect and Action Mechanisms of Oligochitosan on Control of Stem Dry Rot of Zanthoxylum bungeanum. AB - In this report, the effects of two oligochitosans, i.e., oligochitosan A (OCHA) and oligochitosan B (OCHB), on control of dry rot of Zanthoxylum bungeanum (Z. bungeanum) caused by Fusarium sambucinum (F. sambucinum) were evaluated. First, both oligochitosans show desirable ability to decrease the infection of F. sambucinum. Second, the oligochitosans strongly inhibit the radial colony and submerged biomass growth of F. sambucinum. Lastly, these oligochitosans are capable of increasing the activities of phenylalanine ammonia lyase (PAL), polyphenoloxidase (PPO) and peroxidase (POD) significantly, as well as enhancing the content of total phenolics in Z. bungeanum stems. These findings indicate that the protective effects of OCHA and OCHB on Z. bungeanum stems against dry rot may be associated with the direct fungitoxic function against pathogen and the elicitation of biochemical defensive responses in Z. bungeanum stems. The outcome of this report suggests that oligochitosans may serve as a promising natural fungicide to substitute, at least partially, for synthetic fungicides in the disease management of Z. bungeanum. PMID- 27376269 TI - Clinical Application of Human Urinary Extracellular Vesicles in Kidney and Urologic Diseases. AB - Extracellular vesicles (EVs) have been isolated in different body fluids, including urine. The cargo of urinary EVs is composed of nucleic acids and proteins reflecting the physiological and possibly pathophysiological state of cells lining the nephron and the urinary tract. Urinary EVs have been confirmed to contain low amounts of various types of RNA that play a role in intercellular communication by transferring genetic information. This communication through EV RNAs includes both continuation of normal physiological processes and conditioning in disease mechanisms. Although proteins included in urinary EVs represent only 3% of the whole-urine proteome, urinary EVs can influence cells in the renal epithelia not only by delivering RNA cargo, but also by delivering a wide range of proteins. Since urine is a readily available biofluid, the discovery of EVs has opened a new field of biomarker research. The potential use of urinary EV RNAs and proteins as diagnostic biomarkers for various kidney and urologic diseases is currently being explored. Here, we review recent studies that deal in identifying biomarker candidates for human kidney and urologic diseases using urinary EVs and might help to understand the pathophysiology. PMID- 27376271 TI - Novel NSAID-Derived Drugs for the Potential Treatment of Alzheimer's Disease. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested for the potential treatment of neurodegenerative diseases, such as Alzheimer's disease (AD). Prolonged use of NSAIDs, however, produces gastrointestinal (GI) toxicity. To overcome this serious limitation, the aim of this study was to develop novel NSAID-derived drug conjugates (Anti-inflammatory-Lipoyl derivatives, AL4-9) that preserve the beneficial effects of NSAIDS without causing GI problems. As such, we conjugated selected well-known NSAIDs, such as (S)-naproxen and (R) flurbiprofen, with (R)-alpha-lipoic acid (LA) through alkylene diamine linkers. The selection of the antioxidant LA was based on the proposed role of oxidative stress in the development and/or progression of AD. Our exploratory studies revealed that AL7 containing the diaminoethylene linker between (R)-flurbiprofen and LA had the most favorable chemical and in vitro enzymatic stability profiles among the synthesized compounds. Upon pretreatment, this compound exhibited excellent antioxidant activity in phorbol 12-miristate 13-acetate (PMA) stimulated U937 cells (lymphoblast lung from human) and Abeta(25-35)-treated THP 1 cells (leukemic monocytes). Furthermore, AL7 also modulated the expression of COX-2, IL-1beta and TNF-alpha in these cell lines, suggesting anti-inflammatory activity. Taken together, AL7 has emerged as a potential lead worthy of further characterization and testing in suitable in vivo models of AD. PMID- 27376272 TI - Demethyleneberberine Protects against Hepatic Fibrosis in Mice by Modulating NF kappaB Signaling. AB - Demethyleneberberine (DMB) is an essential metabolite of Berberine (BBR) in vivo. Recent reports have revealed multiple novel therapeutic applications of BBR. However, the pharmacological activities of DMB remain to be elucidated. This study aimed to demonstrate the hepatoprotective and anti-fibrotic effects of DMB both in vitro and in vivo. Here we showed that DMB protects against thioacetamide (TAA)-induced hepatic fibrosis in mice and exhibits a higher safety profile as compared to BBR. Flow cytometry and Western blotting analysis showed that DMB is able to suppress the activation of hepatic stellate cells (HSCs) and induce cell apoptosis through the nuclear factor-kappaB (NF-kappaB) cascade. Immunohistochemical (IHC) and quantitative polymerase chain reaction (qPCR) analysis indicated that DMB also has inhibitory effects on collagen synthesis and is able to increase collagen degradation by blocking the transforming growth factor beta 1 (TGF-beta1)-Smad signaling and reducing the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMP (TIMPs). These findings indicate that DMB has the potential to attenuate hepatic fibrosis via suppressing HSC activation. PMID- 27376274 TI - Age-Specific Lipid and Fatty Acid Profiles of Atlantic Salmon Juveniles in the Varzuga River. AB - The age-specific lipid and fatty acid profiles of juvenile Atlantic salmon at different ages (0+, 1+, and 2+ years) after hatching from nests located in the mainstream of a large Arctic River, the Varzuga River, and resettling to the favorable Sobachji shoal in autumn before overwinter are herein presented. The contemporary methods of the lipid analysis were used: thin layer chromatography and gas chromatography. The results show that the stability of the regulation of important functions in developing organisms is maintained through structural alterations in lipids. These alterations can be considered as a sequence of the modifications and changes in the ratios of certain lipid classes and fatty acids constituents. In general, changes in the lipids and fatty acids (FAs) maintained the physiological limits and controls through the adaptive systems of the organism. The mechanisms of juvenile fish biochemical adaptation to the environmental conditions in the studied biotope include the modification of the energy metabolism and anabolism, and here belongs to the energy characteristics of metabolic processes. PMID- 27376273 TI - Cell Models and Their Application for Studying Adipogenic Differentiation in Relation to Obesity: A Review. AB - Over the last several years, the increasing prevalence of obesity has favored an intense study of adipose tissue biology and the precise mechanisms involved in adipocyte differentiation and adipogenesis. Adipocyte commitment and differentiation are complex processes, which can be investigated thanks to the development of diverse in vitro cell models and molecular biology techniques that allow for a better understanding of adipogenesis and adipocyte dysfunction associated with obesity. The aim of the present work was to update the different animal and human cell culture models available for studying the in vitro adipogenic differentiation process related to obesity and its co-morbidities. The main characteristics, new protocols, and applications of the cell models used to study the adipogenesis in the last five years have been extensively revised. Moreover, we depict co-cultures and three-dimensional cultures, given their utility to understand the connections between adipocytes and their surrounding cells in adipose tissue. PMID- 27376275 TI - Analysis of the Interaction of Dp44mT with Human Serum Albumin and Calf Thymus DNA Using Molecular Docking and Spectroscopic Techniques. AB - Di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT) exhibits significant antitumor activity. However, the mechanism of its pharmacological interaction with human serum albumin (HSA) and DNA remains poorly understood. Here, we aimed to elucidate the interactions of Dp44mT with HSA and DNA using MTT assays, spectroscopic methods, and molecular docking analysis. Our results indicated that addition of HSA at a ratio of 1:1 did not alter the cytotoxicity of Dp44mT, but did affect the cytotoxicity of the Dp44mT-Cu complex. Data from fluorescence quenching and UV-VIS absorbance measurements demonstrated that Dp44mT could bind to HSA with a moderate affinity (Ka = approximately 104 M(-1)). CD spectra revealed that Dp44mT could slightly disrupt the secondary structure of HSA. Dp44mT could also interact with Ct-DNA, but had a moderate binding constant (KEB = approximately 104 M(-1)). Docking studies indicated that the IB site of HSA, but not the IIA and IIIA sites, could be favorable for Dp44mT and that binding of Dp44mT to HSA involved hydrogen bonds and hydrophobic force, consistent with thermodynamic results from spectral investigations. Thus, the moderate binding affinity of Dp44mT with HSA and DNA partially contributed to its antitumor activity and may be preferable in drug design approaches. PMID- 27376276 TI - Plasma Folate and Vitamin B12 Levels in Patients with Hepatocellular Carcinoma. AB - Folate and vitamin B12 involved in the one-carbon metabolism may play a key role in carcinogenesis and progression of hepatocellular carcinoma (HCC) through influencing DNA integrity. The purpose of this study is to evaluate the association of plasma folate and vitamin B12 levels with HCC in a case-control study on 312 HCC patients and 325 cancer-free controls. Plasma concentrations of folate and vitamin B12 in all the subjects were measured by electrochemiluminescence immunoassay. Meanwhile, the information of HCC patients' clinical characteristics including tumor-node-metastasis (TNM) stage, tumor size and tumor markers were collected. The patients of HCC had significantly lower folate levels than those of controls; there was no significant difference in the mean of plasma vitamin B12 levels. We also observed an inverse association between the levels of plasma folate and HCC: the adjusted odds ratios (OR) (95% confidence intervals (CI)) of HCC from the highest to lowest quartile of folate were 0.30 (0.15-0.60), 0.33 (0.17-0.65), and 0.19 (0.09-0.38). Compared to the subjects in the lowest quartile of plasma vitamin B12, only the subjects in the highest quartile of vitamin B12 exhibited a significant positive relationship with HCC, the adjusted OR was 2.01 (95% CI, 1.02-3.98). HCC patients with Stage III and IV or bigger tumor size had lower folate and higher vitamin B12 levels. There was no significant difference in the mean plasma folate levels of the HCC cases in tumor markers status (AFP, CEA and CA19-9 levels), whereas patients with higher CEA or CA19-9 levels retained significantly more plasma vitamin B12 than those with normal-CEA or CA19-9 level. In conclusion, plasma folate and vitamin B12 levels could be associated with HCC, and might be used as predictors of clinical characteristics of HCC patients. However, further prospective studies are essential to confirm the observed results. PMID- 27376278 TI - Phase Transitions of Isotropic to Anisotropic Biocompatible Lipid-Based Drug Delivery Systems Overcoming Insoluble Benznidazole Loading. AB - Previous studies reported low benznidazole (BNZ) loading in conventional emulsions due to the weak interaction of the drug with the most common oils used to produce foods or pharmaceuticals. In this study, we focused on how the type of surfactant, surfactant-to-oil ratio w/w (SOR) and oil-to-water ratio w/w (OWR) change the phase behavior of different lipid-based drug delivery systems (LBDDS) produced by emulsion phase inversion. The surfactant mixture composed of soy phosphatidylcholine and sodium oleate (1:7, w/w, hydrophilic lipophilic balance = 16) stabilized medium chain triglyceride in water. Ten formulations with the clear aspect or less turbid dispersions (five with the SOR ranging from 0.5 to 2.5 and five with the OWR from 0.06 to 0.4) were selected from the phase behavior diagram to assess structural features and drug-loading capacity. The rise in the SOR induced the formation of distinct lipid-based drug delivery systems (nanoemulsions and liquid crystal lamellar type) that were identified using rheological measurements and cross-polarized light microscopy images. Clear dispersions of small and narrow droplet-sized liquid-like nanoemulsions, Newtonian flow-type, were produced at SOR from 0.5 to 1.5 and OWR from 0.12 to 0.4, while clear liquid or gel-like liquid crystals were produced at SOR from 1.5 to 2.5. The BNZ loading was improved according to the composition and type of LBDDS produced, suggesting possible drug location among surfactant layers. The cell viability assays proved the biocompatibility for all of the prepared nanoemulsions at SOR less than 1.5 and liquid crystals at SOR less than 2.5, demonstrating their promising features for the oral or parenteral colloidal delivery systems containing benznidazole for Chagas disease treatment. PMID- 27376279 TI - In Situ Electron Microscopy of Lactomicroselenium Particles in Probiotic Bacteria. AB - Electron microscopy was used to test whether or not (a) in statu nascendi synthesized, and in situ measured, nanoparticle size does not differ significantly from the size of nanoparticles after their purification; and (b) the generation of selenium is detrimental to the bacterial strains that produce them. Elemental nano-sized selenium produced by probiotic latic acid bacteria was used as a lactomicroselenium (lactomicroSel) inhibitor of cell growth in the presence of lactomicroSel, and was followed by time-lapse microscopy. The size of lactomicroSel produced by probiotic bacteria was measured in situ and after isolation and purification. For these measurements the TESLA BS 540 transmission electron microscope was converted from analog (aTEM) to digital processing (dTEM), and further to remote-access internet electron microscopy (iTEM). Lactobacillus acidophilus produced fewer, but larger, lactomicroSel nanoparticles (200-350 nm) than Lactobacillus casei (L. casei), which generated many, smaller lactomicroSel particles (85-200 nm) and grains as a cloudy, less electrodense material. Streptococcus thermophilus cells generated selenoparticles (60-280 nm) in a suicidic manner. The size determined in situ in lactic acid bacteria was significantly lower than those measured by scanning electron microscopy after the isolation of lactomicroSel particles obtained from lactobacilli (100-500 nm), but higher relative to those isolated from Streptococcus thermopilus (50-100 nm). These differences indicate that smaller lactomicroSel particles could be more toxic to the producing bacteria themselves and discrepancies in size could have implications with respect to the applications of selenium nanoparticles as prebiotics. PMID- 27376277 TI - Role of Aquaporins in a Composite Model of Water Transport in the Leaf. AB - Water-transport pathways through the leaf are complex and include several checkpoints. Some of these checkpoints exhibit dynamic behavior that may be regulated by aquaporins (AQPs). To date, neither the relative weight of the different water pathways nor their molecular mechanisms are well understood. Here, we have collected evidence to support a putative composite model of water pathways in the leaf and the distribution of water across those pathways. We describe how water moves along a single transcellular path through the parenchyma and continues toward the mesophyll and stomata along transcellular, symplastic and apoplastic paths. We present evidence that points to a role for AQPs in regulating the relative weight of each path in the overall leaf water-transport system and the movement of water between these paths as a result of the integration of multiple signals, including transpiration demand, water potential and turgor. We also present a new theory, the hydraulic fuse theory, to explain effects of the leaf turgor-loss-point on water paths alternation and the subsequent reduction in leaf hydraulic conductivity. An improved understating of leaf water-balance management may lead to the development of crops that use water more efficiently, and responds better to environmental changes. PMID- 27376280 TI - The Salicylic Acid-Mediated Release of Plant Volatiles Affects the Host Choice of Bemisia tabaci. AB - The whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) causes serious crop losses worldwide by transmitting viruses. We have previously shown that salicylic acid (SA)-related plant defenses directly affect whiteflies. In this study, we applied exogenous SA to tomato plants in order to investigate the interaction between SA-induced plant volatiles and nonviruliferous B. tabaci B and Q or B- and Q-carrying tomato yellow leaf curl virus (TYLCV). The results showed that exogenous SA caused plants to repel nonviruliferous whiteflies, but the effect was reduced when the SA concentration was low and when the whiteflies were viruliferous. Exogenous SA increased the number and quantity of plant volatiles-especially the quantity of methyl salicylate and delta-limonene. In Y tube olfactometer assays, methyl salicylate and delta-limonene repelled the whiteflies, but the repellency was reduced for viruliferous Q. We suggest that the release of plant volatiles as mediated by SA affects the interaction between whiteflies, plants, and viruses. Further studies are needed to determine why viruliferous Q is less sensitive than nonviruliferous Q to repellent plant volatiles. PMID- 27376282 TI - Analysis of the Mitochondrial Genome in Hypomyces aurantius Reveals a Novel Twintron Complex in Fungi. AB - Hypomyces aurantius is a mycoparasite that causes cobweb disease, a most serious disease of cultivated mushrooms. Intra-species identification is vital for disease control, however the lack of genomic data makes development of molecular markers challenging. Small size, high copy number, and high mutation rate of fungal mitochondrial genome makes it a good candidate for intra and inter species differentiation. In this study, the mitochondrial genome of H. H.a0001 was determined from genomic DNA using Illumina sequencing. The roughly 72 kb genome shows all major features found in other Hypocreales: 14 common protein genes, large and small subunit rRNAs genes and 27 tRNAs genes. Gene arrangement comparison showed conserved gene orders in Hypocreales mitochondria are relatively conserved, with the exception of Acremonium chrysogenum and Acremonium implicatum. Mitochondrial genome comparison also revealed that intron length primarily contributes to mitogenome size variation. Seventeen introns were detected in six conserved genes: five in cox1, four in rnl, three in cob, two each in atp6 and cox3, and one in cox2. Four introns were found to contain two introns or open reading frames: cox3-i2 is a twintron containing two group IA type introns; cox2-i1 is a group IB intron encoding two homing endonucleases; and cox1-i4 and cox1-i3 both contain two open reading frame (ORFs). Analyses combining secondary intronic structures, insertion sites, and similarities of homing endonuclease genes reveal two group IA introns arranged side by side within cox3-i2. Mitochondrial data for H. aurantius provides the basis for further studies relating to population genetics and species identification. PMID- 27376281 TI - Roles of d-Amino Acids on the Bioactivity of Host Defense Peptides. AB - Host defense peptides (HDPs) are positively-charged and amphipathic components of the innate immune system that have demonstrated great potential to become the next generation of broad spectrum therapeutic agents effective against a vast array of pathogens and tumor. As such, many approaches have been taken to improve the therapeutic efficacy of HDPs. Amongst these methods, the incorporation of d amino acids (d-AA) is an approach that has demonstrated consistent success in improving HDPs. Although, virtually all HDP review articles briefly mentioned about the role of d-AA, however it is rather surprising that no systematic review specifically dedicated to this topic exists. Given the impact that d-AA incorporation has on HDPs, this review aims to fill that void with a systematic discussion of the impact of d-AA on HDPs. PMID- 27376283 TI - Discovery of a Potential HER2 Inhibitor from Natural Products for the Treatment of HER2-Positive Breast Cancer. AB - Breast cancer is one of the most lethal types of cancer in women worldwide due to the late stage detection and resistance to traditional chemotherapy. The human epidermal growth factor receptor 2 (HER2) is considered as a validated target in breast cancer therapy. Even though a substantial effort has been made to develop HER2 inhibitors, only lapatinib has been approved by the U.S. Food and Drug Administration (FDA). Side effects were observed in a majority of the patients within one year of treatment initiation. Here, we took advantage of bioinformatics tools to identify novel effective HER2 inhibitors. The structure based virtual screening combined with ADMET (absorption, distribution, metabolism, excretion and toxicity) prediction was explored. In total, 11,247 natural compounds were screened. The top hits were evaluated by an in vitro HER2 kinase inhibition assay. The cell proliferation inhibition effect of identified inhibitors was evaluated in HER2-overexpressing SKBR3 and BT474 cell lines. We found that ZINC15122021 showed favorable ADMET properties and attained high binding affinity against HER2. Moreover, ZINC15122021 showed high kinase inhibition activity against HER2 and presented outstanding cell proliferation inhibition activity against both SKBR3 and BT474 cell lines. Results reveal that ZINC15122021 can be a potential HER2 inhibitor. PMID- 27376284 TI - Effects and Mechanisms of Low-Intensity Pulsed Ultrasound for Chronic Prostatitis and Chronic Pelvic Pain Syndrome. AB - Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is one of the most common urologic diseases, and no curative treatments have been identified. Low intensity pulsed ultrasound (LIPUS) has been successfully used in promoting tissue healing, inhibiting inflammation and pain, differentiating stem cells, and stimulating nerve regeneration/muscle regeneration, as well as enhancing angiogenesis. Very recently, LIPUS has been proven an effective approach for CP/CPPS. This review summarizes the possible mechanisms responsible for the therapeutic effect of LIPUS for CP/CPPS. To search publications relevant to the topics of this review, the search engine for life sciences of Entrez was used. We reviewed the available evidence from 1954 through 2015 concerning LIPUS for CP/CPPS. According to the literature, both transrectal and transperineal approaches of LIPUS are effective for CP/CPPS. PMID- 27376285 TI - Increased Efficacy of Brentuximab Vedotin (SGN-35) in Combination with Cytokine Induced Killer Cells in Lymphoma. AB - Brentuximab vedotin (SGN-35) is an antibody-drug conjugate with a high selectivity against CD30+ cell lines and more than 300-fold less activity against antigen-negative cells. In the last years, the results of many in vitro and in vivo studies have led to the fast approval of this drug to treat lymphoma patients. Another innovative method to treat tumor cells including lymphoma cells is the use cytokine-induced killer (CIK) cells, which have also been approved and proven to be a safe treatment with only minor adverse events. In this study, a possible additive effect when combining SGN-35 with CIK cells was investigated. The combinational treatment showed that it reduces the viability of CD30+ cell lines significantly in vitro. Additionally, the amount of lymphoma cells was significantly reduced when exposed to CIK cells as well as when exposed to SGN 35. A significant negative effect of SGN-35 on the function of CIK cells could be excluded. These results lead to the assumption that SGN-35 and CIK cells in combination might achieve better results in an in vitro setting compared to the single use of SGN-35 and CIK cells. Further investigations in in vivo models must be conducted to obtain a better understanding of the exact mechanisms of both treatments when applied in combination. PMID- 27376287 TI - Molecularly Imprinted Polymer Nanoparticles for Formaldehyde Sensing with QCM. AB - Herein, we report on molecularly imprinted polymers (MIPs) for detecting formaldehyde vapors in air streams. A copolymer thin film consisting of styrene, methacrylic acid, and ethylene glycol dimethacrylate on quartz crystal microbalance (QCM) yielded a detection limit of 500 ppb formaldehyde in dry air. Surprisingly, these MIPs showed specific behavior when tested against a range of volatile organic compounds (VOCs), such as acetaldehyde, methanol, formic acid, and dichloromethane. Despite thus being a suitable receptor in principle, the MIPs were not useful for measurements at 50% humidity due to surface saturation by water. This was overcome by introducing primary amino groups into the polymer via allyl amine and by changing the coating morphology from thin film to nanoparticles. This led to the same limit of detection (500 ppb) and selectivity as before, but at the real-life conditions of 50% relative humidity. PMID- 27376286 TI - Transcriptome Sequencing Analyses between the Cytoplasmic Male Sterile Line and Its Maintainer Line in Welsh Onion (Allium fistulosum L.). AB - Cytoplasmic male sterility (CMS) is important for exploiting heterosis in crop plants and also serves as a model for investigating nuclear-cytoplasmic interaction. The molecular mechanism of cytoplasmic male sterility and fertility restoration was investigated in several important economic crops but remains poorly understood in the Welsh onion. Therefore, we compared the differences between the CMS line 64-2 and its maintainer line 64-1 using transcriptome sequencing with the aim of determining critical genes and pathways associated with male sterility. This study combined two years of RNA-seq data; there were 1504 unigenes (in May 2013) and 2928 unigenes (in May 2014) that were differentially expressed between the CMS and cytoplasmic male maintainer Welsh onion varieties. Known CMS-related genes were found in the set of differentially expressed genes and checked by qPCR. These genes included F-type ATPase, NADH dehydrogenase, cytochrome c oxidase, etc. Overall, this study demonstrated that the CMS regulatory genes and pathways may be associated with the mitochondria and nucleus in the Welsh onion. We believe that this transcriptome dataset will accelerate the research on CMS gene clones and other functional genomics research on A. fistulosum L. PMID- 27376288 TI - Robust Behavior Recognition in Intelligent Surveillance Environments. AB - Intelligent surveillance systems have been studied by many researchers. These systems should be operated in both daytime and nighttime, but objects are invisible in images captured by visible light camera during the night. Therefore, near infrared (NIR) cameras, thermal cameras (based on medium-wavelength infrared (MWIR), and long-wavelength infrared (LWIR) light) have been considered for usage during the nighttime as an alternative. Due to the usage during both daytime and nighttime, and the limitation of requiring an additional NIR illuminator (which should illuminate a wide area over a great distance) for NIR cameras during the nighttime, a dual system of visible light and thermal cameras is used in our research, and we propose a new behavior recognition in intelligent surveillance environments. Twelve datasets were compiled by collecting data in various environments, and they were used to obtain experimental results. The recognition accuracy of our method was found to be 97.6%, thereby confirming the ability of our method to outperform previous methods. PMID- 27376289 TI - An Improved Simulated Annealing Technique for Enhanced Mobility in Smart Cities. AB - Vehicular traffic congestion is a significant problem that arises in many cities. This is due to the increasing number of vehicles that are driving on city roads of limited capacity. The vehicular congestion significantly impacts travel distance, travel time, fuel consumption and air pollution. Avoidance of traffic congestion and providing drivers with optimal paths are not trivial tasks. The key contribution of this work consists of the developed approach for dynamic calculation of optimal traffic routes. Two attributes (the average travel speed of the traffic and the roads' length) are utilized by the proposed method to find the optimal paths. The average travel speed values can be obtained from the sensors deployed in smart cities and communicated to vehicles via the Internet of Vehicles and roadside communication units. The performance of the proposed algorithm is compared to three other algorithms: the simulated annealing weighted sum, the simulated annealing technique for order preference by similarity to the ideal solution and the Dijkstra algorithm. The weighted sum and technique for order preference by similarity to the ideal solution methods are used to formulate different attributes in the simulated annealing cost function. According to the Sheffield scenario, simulation results show that the improved simulated annealing technique for order preference by similarity to the ideal solution method improves the traffic performance in the presence of congestion by an overall average of 19.22% in terms of travel time, fuel consumption and CO2 emissions as compared to other algorithms; also, similar performance patterns were achieved for the Birmingham test scenario. PMID- 27376290 TI - An Energy-Efficient Game-Theory-Based Spectrum Decision Scheme for Cognitive Radio Sensor Networks. AB - A cognitive radio sensor network (CRSN) is a wireless sensor network in which sensor nodes are equipped with cognitive radio. In this paper, we propose an energy-efficient game-theory-based spectrum decision (EGSD) scheme for CRSNs to prolong the network lifetime. Note that energy efficiency is the most important design consideration in CRSNs because it determines the network lifetime. The central part of the EGSD scheme consists of two spectrum selection algorithms: random selection and game-theory-based selection. The EGSD scheme also includes a clustering algorithm, spectrum characterization with a Markov chain, and cluster member coordination. Our performance study shows that EGSD outperforms the existing popular framework in terms of network lifetime and coordination overhead. PMID- 27376291 TI - Development of a Nafion/MWCNT-SPCE-Based Portable Sensor for the Voltammetric Analysis of the Anti-Tuberculosis Drug Ethambutol. AB - Herein we describe the development, characterization and application of an electrochemical sensor based on the use of Nafion/MWCNT-modified screen-printed carbon electrodes (SPCEs) for the voltammetric detection of the anti-tuberculosis (anti-TB) drug ethambutol (ETB). The electrochemical behaviour of the drug at the surface of the developed Nafion/MWCNT-SPCEs was studied through cyclic voltammetry (CV) and square wave voltammetry (SWV) techniques. Electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM) were employed to characterize the modified surface of the electrodes. Results showed that, compared to both unmodified and MWCNTs-modified SPCEs, negatively charged Nafion/MWCNT-SPCEs remarkably enhanced the electrochemical sensitivity and selectivity for ETB due to the synergistic effect of the electrostatic interaction between cationic ETB molecules and negatively charged Nafion polymer and the inherent electrocatalytic properties of both MWCNTs and Nafion. Nafion/MWCNT-SPCEs provided excellent biocompatibility, good electrical conductivity, low electrochemical interferences and a high signal-to-noise ratio, providing excellent performance towards ETB quantification in microvolumes of human urine and human blood serum samples. The outcomes of this paper confirm that the Nafion/MWCNT-SPCE-based device could be a potential candidate for the development of a low-cost, yet reliable and efficient electrochemical portable sensor for the low-level detection of this antimycobacterial drug in biological samples. PMID- 27376292 TI - Classification of Kiwifruit Grades Based on Fruit Shape Using a Single Camera. AB - This study aims to demonstrate the feasibility for classifying kiwifruit into shape grades by adding a single camera to current Chinese sorting lines equipped with weight sensors. Image processing methods are employed to calculate fruit length, maximum diameter of the equatorial section, and projected area. A stepwise multiple linear regression method is applied to select significant variables for predicting minimum diameter of the equatorial section and volume and to establish corresponding estimation models. Results show that length, maximum diameter of the equatorial section and weight are selected to predict the minimum diameter of the equatorial section, with the coefficient of determination of only 0.82 when compared to manual measurements. Weight and length are then selected to estimate the volume, which is in good agreement with the measured one with the coefficient of determination of 0.98. Fruit classification based on the estimated minimum diameter of the equatorial section achieves a low success rate of 84.6%, which is significantly improved using a linear combination of the length/maximum diameter of the equatorial section and projected area/length ratios, reaching 98.3%. Thus, it is possible for Chinese kiwifruit sorting lines to reach international standards of grading kiwifruit on fruit shape classification by adding a single camera. PMID- 27376293 TI - Joint Parameter Estimation for the Two-Wave with Diffuse Power Fading Model. AB - Wireless sensor networks deployed within metallic cavities are known to suffer from a very severe fading, even in strong line-of-sight propagation conditions. This behavior is well-captured by the Two-Wave with Diffuse Power (TWDP) fading distribution, which shows great fit to field measurements in such scenarios. In this paper, we address the joint estimation of the parameters K and Delta that characterize the TWDP fading model, based on the observation of the received signal envelope. We use a moment-based approach to derive closed-form expressions for the estimators of K and Delta, as well as closed-form expressions for their asymptotic variance. Results show that the estimation error is close to the Cramer-Rao lower bound for a wide range of values of the parameters K and Delta. The performance degradation due to a finite number of observations is also analyzed. PMID- 27376294 TI - Parameter Estimation of a Ground Moving Target Using Image Sharpness Optimization. AB - Motion parameter estimation of a ground moving target is an important issue in synthetic aperture radar ground moving target indication (SAR-GMTI) which has significant applications for civilian and military. The SAR image of a moving target may be displaced and defocused due to the radial and along-track velocity components, respectively. The sharpness cost function presents a measure of the degree of focus of the image. In this work, a new ground moving target parameter estimation algorithm based on the sharpness optimization criterion is proposed. The relationships between the quadratic phase errors and the target's velocity components are derived. Using two-dimensional searching of the sharpness cost function, we can obtain the velocity components of the target and the focused target image simultaneously. The proposed moving target parameter estimation method and image sharpness metrics are analyzed in detail. Finally, numerical results illustrate the effective and superior velocity estimation performance of the proposed method when compared to existing algorithms. PMID- 27376295 TI - A Novel Pre-Processing Technique for Original Feature Matrix of Electronic Nose Based on Supervised Locality Preserving Projections. AB - An electronic nose (E-nose) consisting of 14 metal oxide gas sensors and one electronic chemical gas sensor has been constructed to identify four different classes of wound infection. However, the classification results of the E-nose are not ideal if the original feature matrix containing the maximum steady-state response value of sensors is processed by the classifier directly, so a novel pre processing technique based on supervised locality preserving projections (SLPP) is proposed in this paper to process the original feature matrix before it is put into the classifier to improve the performance of the E-nose. SLPP is good at finding and keeping the nonlinear structure of data; furthermore, it can provide an explicit mapping expression which is unreachable by the traditional manifold learning methods. Additionally, some effective optimization methods are found by us to optimize the parameters of SLPP and the classifier. Experimental results prove that the classification accuracy of support vector machine (SVM combined with the data pre-processed by SLPP outperforms other considered methods. All results make it clear that SLPP has a better performance in processing the original feature matrix of the E-nose. PMID- 27376296 TI - Sequential Total Variation Denoising for the Extraction of Fetal ECG from Single Channel Maternal Abdominal ECG. AB - Fetal heart rate (FHR) is an important determinant of fetal health. Cardiotocography (CTG) is widely used for measuring the FHR in the clinical field. However, fetal movement and blood flow through the maternal blood vessels can critically influence Doppler ultrasound signals. Moreover, CTG is not suitable for long-term monitoring. Therefore, researchers have been developing algorithms to estimate the FHR using electrocardiograms (ECGs) from the abdomen of pregnant women. However, separating the weak fetal ECG signal from the abdominal ECG signal is a challenging problem. In this paper, we propose a method for estimating the FHR using sequential total variation denoising and compare its performance with that of other single-channel fetal ECG extraction methods via simulation using the Fetal ECG Synthetic Database (FECGSYNDB). Moreover, we used real data from PhysioNet fetal ECG databases for the evaluation of the algorithm performance. The R-peak detection rate is calculated to evaluate the performance of our algorithm. Our approach could not only separate the fetal ECG signals from the abdominal ECG signals but also accurately estimate the FHR. PMID- 27376297 TI - Heterogeneous Multi-Robot System for Mapping Environmental Variables of Greenhouses. AB - The productivity of greenhouses highly depends on the environmental conditions of crops, such as temperature and humidity. The control and monitoring might need large sensor networks, and as a consequence, mobile sensory systems might be a more suitable solution. This paper describes the application of a heterogeneous robot team to monitor environmental variables of greenhouses. The multi-robot system includes both ground and aerial vehicles, looking to provide flexibility and improve performance. The multi-robot sensory system measures the temperature, humidity, luminosity and carbon dioxide concentration in the ground and at different heights. Nevertheless, these measurements can be complemented with other ones (e.g., the concentration of various gases or images of crops) without a considerable effort. Additionally, this work addresses some relevant challenges of multi-robot sensory systems, such as the mission planning and task allocation, the guidance, navigation and control of robots in greenhouses and the coordination among ground and aerial vehicles. This work has an eminently practical approach, and therefore, the system has been extensively tested both in simulations and field experiments. PMID- 27376298 TI - A Distributed Learning Method for l 1 -Regularized Kernel Machine over Wireless Sensor Networks. AB - In wireless sensor networks, centralized learning methods have very high communication costs and energy consumption. These are caused by the need to transmit scattered training examples from various sensor nodes to the central fusion center where a classifier or a regression machine is trained. To reduce the communication cost, a distributed learning method for a kernel machine that incorporates l 1 norm regularization ( l 1 -regularized) is investigated, and a novel distributed learning algorithm for the l 1 -regularized kernel minimum mean squared error (KMSE) machine is proposed. The proposed algorithm relies on in network processing and a collaboration that transmits the sparse model only between single-hop neighboring nodes. This paper evaluates the proposed algorithm with respect to the prediction accuracy, the sparse rate of model, the communication cost and the number of iterations on synthetic and real datasets. The simulation results show that the proposed algorithm can obtain approximately the same prediction accuracy as that obtained by the batch learning method. Moreover, it is significantly superior in terms of the sparse rate of model and communication cost, and it can converge with fewer iterations. Finally, an experiment conducted on a wireless sensor network (WSN) test platform further shows the advantages of the proposed algorithm with respect to communication cost. PMID- 27376299 TI - Single-Use Disposable Electrochemical Label-Free Immunosensor for Detection of Glycated Hemoglobin (HbA1c) Using Differential Pulse Voltammetry (DPV). AB - A single-use disposable in vitro electrochemical immunosensor for the detection of HbA1c in undiluted human serum using differential pulse voltammetry (DPV) was developed. A three-electrode configuration electrochemical biosensor consisted of 10-nm-thin gold film working and counter electrodes and a thick-film printed Ag/AgCl reference electrode was fabricated on a polyethylene terephthalate (PET) substrate. Micro-fabrication techniques including sputtering vapor deposition and thick-film printing were used to fabricate the biosensor. This was a roll-to-roll cost-effective manufacturing process making the single-use disposable in vitro HbA1c biosensor a reality. Self-assembled monolayers of 3-Mercaptopropionic acid (MPA) were employed to covalently immobilize anti-HbA1c on the surface of gold electrodes. Electrochemical impedance spectroscopy (EIS) and X-ray photoelectron spectroscopy (XPS) confirmed the excellent coverage of MPA-SAM and the upward orientation of carboxylic groups. The hindering effect of HbA1c on the ferricyanide/ferrocyanide electron transfer reaction was exploited as the HbA1c detection mechanism. The biosensor showed a linear range of 7.5-20 ug/mL of HbA1c in 0.1 M PBS. Using undiluted human serum as the test medium, the biosensor presented an excellent linear behavior (R2 = 0.999) in the range of 0.1-0.25 mg/mL of HbA1c. The potential application of this biosensor for in vitro measurement of HbA1c for diabetic management was demonstrated. PMID- 27376300 TI - Collaboration-Centred Cities through Urban Apps Based on Open and User-Generated Data. AB - This paper describes the IES Cities platform conceived to streamline the development of urban apps that combine heterogeneous datasets provided by diverse entities, namely, government, citizens, sensor infrastructure and other information data sources. This work pursues the challenge of achieving effective citizen collaboration by empowering them to prosume urban data across time. Particularly, this paper focuses on the query mapper; a key component of the IES Cities platform devised to democratize the development of open data-based mobile urban apps. This component allows developers not only to use available data, but also to contribute to existing datasets with the execution of SQL sentences. In addition, the component allows developers to create ad hoc storages for their applications, publishable as new datasets accessible by other consumers. As multiple users could be contributing and using a dataset, our solution also provides a data level permission mechanism to control how the platform manages the access to its datasets. We have evaluated the advantages brought forward by IES Cities from the developers' perspective by describing an exemplary urban app created on top of it. In addition, we include an evaluation of the main functionalities of the query mapper. PMID- 27376301 TI - Model Study of the Influence of Ambient Temperature and Installation Types on Surface Temperature Measurement by Using a Fiber Bragg Grating Sensor. AB - Surface temperature is an important parameter in clinical diagnosis, equipment state control, and environmental monitoring fields. The Fiber Bragg Grating (FBG) temperature sensor possesses numerous significant advantages over conventional electrical sensors, thus it is an ideal choice to achieve high-accuracy surface temperature measurements. However, the effects of the ambient temperature and installation types on the measurement of surface temperature are often overlooked. A theoretical analysis is implemented and a thermal transfer model of a surface FBG sensor is established. The theoretical and simulated analysis shows that both substrate strain and the temperature difference between the fiber core and hot surface are the most important factors which affect measurement accuracy. A surface-type temperature standard setup is proposed to study the measurement error of the FBG temperature sensor. Experimental results show that there are two effects influencing measurement results. One is the "gradient effect". This results in a positive linear error with increasing surface temperature. Another is the "substrate effect". This results in a negative non-linear error with increasing surface temperature. The measurement error of the FBG sensor with single-ended fixation are determined by the gradient effect and is a linear error. It is not influenced by substrate expansion. Thus, it can be compensated easily. The measurement errors of the FBG sensor with double-ended fixation are determined by the two effects and the substrate effect is dominant. The measurement error change trend of the FBG sensor with fully-adhered fixation is similar to that with double-ended fixation. The adhesive layer can reduce the two effects and measurement error. The fully-adhered fixation has lower error, however, it is easily affected by substrate strain. Due to its linear error and strain-resistant characteristics, the single-ended fixation will play an important role in the FBG sensor encapsulation design field in the near future. PMID- 27376302 TI - Content-Based Multi-Channel Network Coding Algorithm in the Millimeter-Wave Sensor Network. AB - With the development of wireless technology, the widespread use of 5G is already an irreversible trend, and millimeter-wave sensor networks are becoming more and more common. However, due to the high degree of complexity and bandwidth bottlenecks, the millimeter-wave sensor network still faces numerous problems. In this paper, we propose a novel content-based multi-channel network coding algorithm, which uses the functions of data fusion, multi-channel and network coding to improve the data transmission; the algorithm is referred to as content based multi-channel network coding (CMNC). The CMNC algorithm provides a fusion driven model based on the Dempster-Shafer (D-S) evidence theory to classify the sensor nodes into different classes according to the data content. By using the result of the classification, the CMNC algorithm also provides the channel assignment strategy and uses network coding to further improve the quality of data transmission in the millimeter-wave sensor network. Extensive simulations are carried out and compared to other methods. Our simulation results show that the proposed CMNC algorithm can effectively improve the quality of data transmission and has better performance than the compared methods. PMID- 27376303 TI - Field Measurement-Based System Identification and Dynamic Response Prediction of a Unique MIT Building. AB - Tall buildings are ubiquitous in major cities and house the homes and workplaces of many individuals. However, relatively few studies have been carried out to study the dynamic characteristics of tall buildings based on field measurements. In this paper, the dynamic behavior of the Green Building, a unique 21-story tall structure located on the campus of the Massachusetts Institute of Technology (MIT, Cambridge, MA, USA), was characterized and modeled as a simplified lumped mass beam model (SLMM), using data from a network of accelerometers. The accelerometer network was used to record structural responses due to ambient vibrations, blast loading, and the October 16th 2012 earthquake near Hollis Center (ME, USA). Spectral and signal coherence analysis of the collected data was used to identify natural frequencies, modes, foundation rocking behavior, and structural asymmetries. A relation between foundation rocking and structural natural frequencies was also found. Natural frequencies and structural acceleration from the field measurements were compared with those predicted by the SLMM which was updated by inverse solving based on advanced multiobjective optimization methods using the measured structural responses and found to have good agreement. PMID- 27376304 TI - Development of Torque Sensor with High Sensitivity for Joint of Robot Manipulator Using 4-Bar Linkage Shape. AB - The torque sensor is used to measure the joint torque of a robot manipulator. Previous research showed that the sensitivity and the stiffness of torque sensors have trade-off characteristics. Stiffness has to be sacrificed to increase the sensitivity of the sensor. In this research, a new torque sensor with high sensitivity (TSHS) is proposed in order to resolve this problem. The key idea of the TSHS comes from its 4-bar linkage shape in which the angular displacement of a short link is larger than that of a long link. The sensitivity of the torque sensor with a 4-bar link shape is improved without decreasing stiffness. Optimization techniques are applied to maximize the sensitivity of the sensor. An actual TSHS is constructed to verify the validity of the proposed mechanism. Experimental results show that the sensitivity of TSHS can be increased 3.5 times without sacrificing stiffness. PMID- 27376305 TI - The Integration of the Image Sensor with a 3-DOF Pneumatic Parallel Manipulator. AB - The study aims to integrate the image sensor for a three-axial pneumatic parallel manipulator which can pick and place objects automatically by the feature information of the image processed through the SURF algorithm. The SURF algorithm is adopted for defining and matching the features of a target object and an object database. In order to accurately mark the center of target and strengthen the feature matching results, the random sample and consensus method (RANSAC) is utilized. The ASUS Xtion Pro Live depth camera which can directly estimate the 3 D location of the target point is used in this study. A set of coordinate estimation calibrations is developed for enhancing the accuracy of target location estimation. This study also presents hand gesture recognition exploiting skin detection and noise elimination to determine the active finger count for input signals of the parallel manipulator. The end-effector of the parallel manipulator can be manipulated to the desired poses according to the measured finger count. Finally, the proposed methods are successfully to achieve the feature recognition and pick and place of the target object. PMID- 27376306 TI - Design of Diaphragm and Coil for Stable Performance of an Eddy Current Type Pressure Sensor. AB - The aim of this work was to develop an eddy current type pressure sensor and investigate its fundamental characteristics affected by the mechanical and electrical design parameters of sensor. The sensor has two key components, i.e., diaphragm and coil. On the condition that the outer diameter of sensor is 10 mm, two key parts should be designed so as to keep a good linearity and sensitivity. Experiments showed that aluminum is the best target material for eddy current detection. A round-grooved diaphragm is suggested in order to measure more precisely its deflection caused by applied pressures. The design parameters of a round-grooved diaphragm can be selected depending on the measuring requirements. A developed pressure sensor with diaphragm of t = 0.2 mm and w = 1.05 mm was verified to measure pressure up to 10 MPa with very good linearity and errors of less than 0.16%. PMID- 27376307 TI - Production of the Marine Carotenoid Astaxanthin by Metabolically Engineered Corynebacterium glutamicum. AB - Astaxanthin, a red C40 carotenoid, is one of the most abundant marine carotenoids. It is currently used as a food and feed additive in a hundred-ton scale and is furthermore an attractive component for pharmaceutical and cosmetic applications with antioxidant activities. Corynebacterium glutamicum, which naturally synthesizes the yellow C50 carotenoid decaprenoxanthin, is an industrially relevant microorganism used in the million-ton amino acid production. In this work, engineering of a genome-reduced C. glutamicum with optimized precursor supply for astaxanthin production is described. This involved expression of heterologous genes encoding for lycopene cyclase CrtY, beta carotene ketolase CrtW, and hydroxylase CrtZ. For balanced expression of crtW and crtZ their translation initiation rates were varied in a systematic approach using different ribosome binding sites, spacing, and translational start codons. Furthermore, beta-carotene ketolases and hydroxylases from different marine bacteria were tested with regard to efficient astaxanthin production in C. glutamicum. In shaking flasks, the C. glutamicum strains developed here overproduced astaxanthin with volumetric productivities up to 0.4 mg.L(-1).h(-1) which are competitive with current algae-based production. Since C. glutamicum can grow to high cell densities of up to 100 g cell dry weight (CDW).L(-1), the recombinant strains developed here are a starting point for astaxanthin production by C. glutamicum. PMID- 27376309 TI - Seroprevalence of Antibodies against Measles, Rubella and Varicella among Asylum Seekers Arriving in Lower Saxony, Germany, November 2014-October 2015. AB - The number of asylum seekers arriving in Germany has increased rapidly since 2014 and cases of vaccine-preventable diseases at reception centres were reported. Asylum seekers 12 years and older arriving in Lower Saxony were serologically screened for antibodies against measles, rubella and varicella between November 2014 and October 2015. We calculated the seroprevalence from the screening data by disease, country of origin and age group and compared them to literature-based herd immunity thresholds in order to identify immunisation gaps. In total, 23,647 specimens were included in our study. Although the vast majority of asylum seekers tested positive for antibodies against measles, rubella and varicella, the seroprevalences were not sufficient to ensure herd immunity. The seroprevalences varied substantially between countries of origin and increased with age. Immunisation of asylum seekers against measles, rubella and varicella is needed and the detailed information on seroprevalences among subgroups of asylum seekers can be used for targeted immunisations at reception centres. PMID- 27376308 TI - Health Service Utilization and Poor Health Reporting in Asthma Patients. AB - The management and treatment of adult asthma has been associated with utilization of health services. OBJECTIVES: First, to investigate the likelihood of health service utilization, including primary care, emergency department, and hospital stays, among persons diagnosed with an asthma condition relative to those that do not have an asthma condition. Second, to examine the likelihood of poor physical health among asthma respondents relative to those that do not have an asthma condition. Third, to demonstrate that these relationships vary with frequency of utilization. Fourth, to discuss the magnitude of differences in frequent utilization between asthma and non-asthma respondents. DATA SOURCE: Data is derived from a random, stratified sampling of Hampton Roads adults, 18 years and older (n = 1678). STUDY DESIGN: Study participants are interviewed to identify asthma diagnosis, access to primary care, frequency of emergency department utilization, hospital admissions, and days of poor physical health. Odds-ratios establish relationships with the covariates on the outcome variable. FINDINGS: Those with asthma are found more likely (OR 1.50, 95% CI 1.05-2.15) to report poor physical health relative to non-asthma study participants. Further, asthma respondents are found more likely (OR 4.23, 95% CI 1.56-11.69) to frequently utilize primary care that may be associated with the management of the condition and are also more likely to utilize treatment services, such as the emergency department (OR 1.87, 95% CI 1.32-2.65) and hospitalization (OR 2.21, 95% CI 1.39 3.50), associated with acute and episodic care. Further, it is a novel finding that these likelihoods increase with frequency of utilization for emergency department visits and hospital stays. CONCLUSION: Continuity in care and better management of the diseases may result in less demand for emergency department services and hospitalization. Health care systems need to recognize that asthma patients are increasingly more likely to be characterized as frequent utilizers of both primary and emergency department care as the threshold for what constitutes frequent utilization increases. Investments in prevention and better management of the chronic condition may result in less demand for acute care services, especially among high frequency utilizers. PMID- 27376310 TI - Smokers' and E-Cigarette Users' Perceptions about E-Cigarette Warning Statements. AB - Cigarette warning labels are important sources of risk information, but warning research for other tobacco products is limited. This study aimed to gauge perceptions about warnings that may be used for e-cigarettes. We conducted six small focus groups in late 2014/early 2015 with adult current e-cigarette users and cigarette-only smokers. Participants rated and discussed their perceptions of six e-cigarette warning statements, and warnings in two existing Vuse and MarkTen e-cigarette ads. Participants were open to e-cigarette warnings and provided the strongest reactions to statements warning that e-liquid/e-vapor or e-cigarettes can be poisonous, contain toxins, or are "not a safe alternative to smoking". However, many also noted that these statements were exaggerated, potentially misleading, and could scare smokers away from reducing their harm by switching to e-cigarettes. Opinions on the Food and Drug Administration's proposed nicotine addiction warning and warnings that e-cigarettes had not been approved for smoking cessation or had unknown health effects were mixed. Participants perceived MarkTen's advertisement warning to be stronger and more noticeable than Vuse's. Care should be taken in developing e-cigarette warnings given their relative recentness and potential for harm reduction compared to other tobacco products. Additional research, including with varied audiences, would be instructive. PMID- 27376311 TI - Influence of Chicken Manure Fertilization on Antibiotic-Resistant Bacteria in Soil and the Endophytic Bacteria of Pakchoi. AB - Animal manure is commonly used as fertilizer for agricultural crops worldwide, even though it is believed to contribute to the spread of antibiotic resistance from animal intestines to the soil environment. However, it is unclear whether and how there is any impact of manure fertilization on populations and community structure of antibiotic-resistant endophytic bacteria (AREB) in plant tissues. To investigate the effect of manure and organic fertilizer on endophytic bacterial communities, pot experiments were performed with pakchoi grown with the following treatments: (1) non-treated; (2) chicken manure-treated and (3) organic fertilizer-treated. Manure or organic fertilizer significantly increased the abundances of total cultivable endophytic bacteria (TCEB) and AREB in pakchoi, and the effect of chicken manure was greater than that of organic fertilizer. Further, 16S rDNA sequencing and the phylogenetic analysis indicated that chicken manure or organic fertilizer application increased the populations of multiple antibiotic-resistant bacteria (MARB) in soil and multiple antibiotic-resistant endophytic bacteria (MAREB) in pakchoi. The identical multiple antibiotic resistant bacterial populations detected in chicken manure, manure- or organic fertilizer-amended soil and the vegetable endophytic system were Brevundimonas diminuta, Brachybacterium sp. and Bordetella sp., suggesting that MARB from manure could enter and colonize the vegetable tissues through manure fertilization. The fact that some human pathogens with multiple antibiotic resistance were detected in harvested vegetables after growing in manure-amended soil demonstrated a potential threat to human health. PMID- 27376312 TI - How and Why Do Smokers Start Using E-Cigarettes? Qualitative Study of Vapers in London, UK. AB - The aims of the study were to (1) describe how and why smokers start to vape and what products they use; (2) relate findings to the COM-B theory of behaviour change (three conditions are necessary for behaviour change (B): capability (C), opportunity (O), and motivation (M)); and (3) to consider implications for e cigarette policy research. Semi-structured interviews (n = 30) were conducted in London, UK, with smokers or ex-smokers who were currently using or had used e cigarettes. E-cigarette initiation (behaviour) was facilitated by: capability (physical capability to use an e-cigarette and psychological capability to understand that using e-cigarettes was less harmful than smoking); opportunity (physical opportunity to access e-cigarettes in shops, at a lower cost than cigarettes, and to vape in "smoke-free" environments, as well as social opportunity to vape with friends and family); and motivation (automatic motivation including curiosity, and reflective motivation, including self conscious decision-making processes related to perceived health benefits). The application of the COM-B model identified multiple factors that may lead to e cigarette initiation, including those that could be influenced by policy, such as price relative to cigarettes and use in smoke-free environments. The effects of these policies on initiation should be further investigated along with the possible moderating/mediating effects of social support. PMID- 27376313 TI - Meta-Analysis for the Association between Polymorphisms in Interleukin-17A and Risk of Coronary Artery Disease. AB - Coronary artery disease (CAD) is a disease which has become a leading cause of death worldwide. The polymorphisms in Interleukin-17 (IL-17A), including rs2275913, rs3819024, rs3819025, rs3748067, rs8193037, rs4711998, and rs8193036, have been found to be probably associated with the risk of CAD. However, the results were inconsistent and inconclusive. The present study performed a meta analysis to get a more precise and comprehensive estimation of the association between the IL-17A polymorphisms and CAD risk. The Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Databases were searched for related studies. A total of six studies, including 3542 cases and 3212 controls, were identified for the meta-analysis. The main findings of the present meta-analysis show that the TT genotype of IL-17A rs3748067 is associated with a significant lower risk of CAD in the homozygous model odds ratio (OR) (OR = 0.37) in Asians. No significant association was found for rs2275913, rs3819024, rs3819025, rs8193037, rs4711998, and rs8193036 with CAD susceptibility in the overall analysis. However, subgroup analysis indicated a significant decreased risk of CAD for the GG genotype and G allele of rs2275913 in a small sample size group, and a higher risk of CAD for the GG genotype and G allele of rs8193037 in a heterozygous model (OR = 1.56), dominant model (OR = 1.54), and allelic model (OR = 1.47) in Asians. In conclusion, the current meta-analysis suggests a significant relationship between rs3748067, rs8193037, and CAD in Asians, while for rs2275913, rs3819024, rs3819025, rs4711998, rs8193036, no such relations were found. Thus, IL-17A rs3748067 and rs8193037 might be recommended as a predictor for susceptibility of CAD for Asians. However, the results of this meta-analysis are hypothesis generating results which should be interpreted with caution because of the heterogeneity and publication bias among study designs. PMID- 27376314 TI - Sounding the Alarm: Health in the Anthropocene. AB - There is growing scientific and public recognition that human actions, directly and indirectly, have profoundly changed the Earth system, in a still accelerating process, increasingly called the "Anthropocene". Planetary transformation, including of the atmosphere, climate, ecosystems and biodiversity, has enormous implications for human health, many of which are deeply disturbing, especially in low-income settings. A few health consequences of the Anthropocene have been partially recognized, including within environmental epidemiology, but their long term consequences remain poorly understood and greatly under-rated. For example Syria could be a "sentinel" population, giving a glimpse to a much wider dystopian future. Health-Earth is a research network, co-founded in 2014, which seeks, with other groups, to catalyse a powerful curative response by the wider health community. This paper builds on a symposium presented by Health-Earth members at the 2015 conference of the International Society for Environmental Epidemiology. It reviews and synthesizes parts of the large literature relevant to the interaction between the changing Earth system and human health. It concludes that this topic should be prominent within future environmental epidemiology and public health. Created by our species, these challenges may be soluble, but solutions require far more understanding and resources than are currently being made available. PMID- 27376315 TI - Physical Activity Programs with Post-Intervention Follow-Up in Children: A Comprehensive Review According to Categories of Intervention. AB - Only 9% of Canadian children meet the National Guidelines of 60 min of daily moderate-to-vigorous intensity physical activity. The aim of this review is to assess the mid- and long-term effectiveness of physical activity interventions and their impact on cardiovascular risk factors in children. We assessed the success of interventions within three different categories: those using a behavioural and social approach, an informational approach or an environmental approach. The average number of children included in these studies was 860 (range of 30-5106); the age range was from 2 to 18 years; and the mean intervention duration was 1607 min (range of 12-8160 min). The length of follow-up post intervention averaged 13 months (ranging from 0.25 to 96 months). A positive impact on physical activity was found in 74% and on any measured outcomes in 90% of the studies reviewed. However, the benefits of physical activity interventions decreased with longer follow-up. Regardless of the approaches, physical activity interventions improved cardiovascular risk factors. However, the challenge of any program is to maintain beneficial effects once the intervention is completed. These findings will inform the development of future intervention programs in order to optimize sustained cardiovascular benefits. PMID- 27376316 TI - Health Risk Assessment of Heavy Metals in Soils from Witwatersrand Gold Mining Basin, South Africa. AB - The study evaluates the health risk caused by heavy metals to the inhabitants of a gold mining area. In this study, 56 soil samples from five mine tailings and 17 from two mine villages were collected and analyzed for Asernic (As), Lead (Pb), Mercury (Hg), Cadmium (Cd), Chromium (Cr), Cobalt (Co), Nickel (Ni), Copper (Cu) and Zinc (Zn) using ICP-MS. Measured concentrations of these heavy metals were then used to calculate the health risk for adults and children. Their concentrations were such that Cr > Ni > As > Zn > Cu > Co > Pb > Hg > Cd, with As, Cr and Ni higher than permissible levels. For the adult population, the Hazard Index value for all pathways was found to be 2.13, making non-carcinogenic effects significant to the adult population. For children, the Hazard Index value was 43.80, a value >>1, which poses serious non-carcinogenic effect to children living in the gold mining area. The carcinogenic risk was found to be 1.7 * 10( 4) implying that 1 person in every 5882 adults may be affected. In addition, for children, in every 2725 individuals, 1 child may be affected (3.67 * 10(-4)). These carcinogenic risk values were both higher than acceptable values. PMID- 27376317 TI - Community-Based Management of Child Malnutrition in Zambia: HIV/AIDS Infection and Other Risk Factors on Child Survival. AB - (1) BACKGROUND: Supplementary feeding programs (SFPs) are effective in the community-based treatment of moderate acute malnutrition (MAM) and prevention of severe acute malnutrition (SAM); (2) METHODS: A retrospective study was conducted on a sample of 1266 Zambian malnourished children assisted from 2012 to 2014 in the Rainbow Project SFPs. Nutritional status was evaluated according to WHO/Unicef methodology. We performed univariate and multivariate Cox proportional risk regression to identify the main predictors of mortality. In addition, a time to event analysis was performed to identify predictors of failure and time to cure events; (3) RESULTS: The analysis included 858 malnourished children (19 months +/- 9.4; 49.9% males). Program outcomes met international standards with a better performance for MAM compared to SAM. Cox regression identified SAM (3.8; 2.1-6.8), HIV infection (3.1; 1.7-5.5), and WAZ <-3 (3.1; 1.6-5.7) as predictors of death. Time to event showed 80% of children recovered by SAM/MAM at 24 weeks. (4) CONCLUSIONS: Preventing deterioration of malnutrition, coupled to early detection of HIV/AIDS with adequate antiretroviral treatment, and extending the duration of feeding supplementation, could be crucial elements for ensuring full recovery and improve child survival in malnourished Zambian children. PMID- 27376318 TI - Suicide: Incidence or Prevalence? Comments on Hernandez-Alvarado et al. Increase in Suicide Rates by Hanging in the Population of Tabasco, Mexico between 2003 and 2012. Int. J. Environ. Res. Public Health 2016, 13, 552. AB - I recently reviewed the paper published in this journal by Hernandez-Alvarado et al., titled "Increase in Suicide Rates by Hanging in the Population of Tabasco, Mexico between 2003 and 2012" [1], and I noticed that the epidemiological concept "prevalence" is not correctly used.[...]. PMID- 27376319 TI - Response to the Fernandez-Nino Comments on Hernandez-Alvarado et al. Increase in Suicide Rates by Hanging in the Population of Tabasco, Mexico between 2003 and 2012. Int. J. Environ. Res. Public Health 2016, 13, 552. AB - We thank the comments of Fernandez-Nino [1] addressing our article [2] "Increase in Suicide Rates by Hanging in the Population of Tabasco, Mexico between 2003 and 2012", which pointed out that the use of the epidemiological concept "prevalence" is not correctly applied in the present manuscript. PMID- 27376320 TI - Approaches to Children's Exposure Assessment: Case Study with Diethylhexylphthalate (DEHP). AB - Children's exposure assessment is a key input into epidemiology studies, risk assessment and source apportionment. The goals of this article are to describe a methodology for children's exposure assessment that can be used for these purposes and to apply the methodology to source apportionment for the case study chemical, diethylhexylphthalate (DEHP). A key feature is the comparison of total (aggregate) exposure calculated via a pathways approach to that derived from a biomonitoring approach. The 4-step methodology and its results for DEHP are: (1) Prioritization of life stages and exposure pathways, with pregnancy, breast-fed infants, and toddlers the focus of the case study and pathways selected that are relevant to these groups; (2) Estimation of pathway-specific exposures by life stage wherein diet was found to be the largest contributor for pregnant women, breast milk and mouthing behavior for the nursing infant and diet, house dust, and mouthing for toddlers; (3) Comparison of aggregate exposure by pathways vs biomonitoring-based approaches wherein good concordance was found for toddlers and pregnant women providing confidence in the exposure assessment; (4) Source apportionment in which DEHP presence in foods, children's products, consumer products and the built environment are discussed with respect to early life mouthing, house dust and dietary exposure. A potential fifth step of the method involves the calculation of exposure doses for risk assessment which is described but outside the scope for the current case study. In summary, the methodology has been used to synthesize the available information to identify key sources of early life exposure to DEHP. PMID- 27376321 TI - Dairy Intake Enhances Body Weight and Composition Changes during Energy Restriction in 18-50-Year-Old Adults-A Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND/AIMS: A meta-analysis of randomized controlled trials (RCTs) was performed to investigate the effects of dairy food or supplements during energy restriction on body weight and composition in 18-50-year-old. METHODS: RCTs >= 4 weeks comparing the effect of dairy consumption (whole food or supplements) with control diets lower in dairy during energy restriction on body weight, fat and lean mass were identified by searching MEDLINE, EMBASE, Pubmed, Cochrane Central and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) until March 2016. Reports were identified and critically appraised in duplicate. Data were pooled using random-effects meta-analysis. Chi2- and I2 statistics indicated heterogeneity. Dose effect was assessed using meta regression analysis. GRADE guidelines were used to rate the quality (QR) of the evidence considering risk of bias, inconsistency, indirectness, imprecision, publication bias and effect estimates. RESULTS: 27 RCTs were reviewed. Participants consumed between 2 and 4 standard servings/day of dairy food or 20 84 g/day of whey protein compared to low dairy control diets, over a median of 16 weeks. A greater reduction in body weight (-1.16 kg [-1.66, -0.66 kg], p < 0.001, I2 = 11%, QR = high, n = 644) and body fat mass (-1.49 kg [-2.06, -0.92 kg], p < 0.001, I2 = 21%, n = 521, QR = high) were found in studies largely including women (90% women). These effects were absent in studies that imposed resistance training (QR = low-moderate). Dairy intake resulted in smaller loss of lean mass (all trials pooled: 0.36 kg [0.01, 0.71 kg], p = 0.04, I2 = 64%, n = 651, QR = moderate). No between study dose-response effects were seen. CONCLUSIONS: Increased dairy intake as part of energy restricted diets resulted in greater loss in bodyweight and fat mass while attenuating lean mass loss in 18-50-year old adults. Further research in males is needed to investigate sex effects. PMID- 27376322 TI - Protecting Skeletal Muscle with Protein and Amino Acid during Periods of Disuse. AB - Habitual sedentary behavior increases risk of chronic disease, hospitalization and poor quality of life. Short-term bed rest or disuse accelerates the loss of muscle mass, function, and glucose tolerance. Optimizing nutritional practices and protein intake may reduce the consequences of disuse by preserving metabolic homeostasis and muscle mass and function. Most modes of physical inactivity have the potential to negatively impact the health of older adults more than their younger counterparts. Mechanistically, mammalian target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis are negatively affected by disuse. This contributes to reduced muscle quality and is accompanied by impaired glucose regulation. Simply encouraging increased protein and/or energy consumption is a well-intentioned, but often impractical strategy to protect muscle health. Emerging evidence suggests that leucine supplemented meals may partially and temporarily protect skeletal muscle during disuse by preserving anabolism and mitigating reductions in mass, function and metabolic homeostasis. PMID- 27376323 TI - Impact of Food Components on in vitro Calcitonin Gene-Related Peptide Secretion-A Potential Mechanism for Dietary Influence on Migraine. AB - Calcitonin gene-related peptide (CGRP) is a pivotal messenger in the inflammatory process in migraine. Limited evidence indicates that diet impacts circulating levels of CGRP, suggesting that certain elements in the diet may influence migraine outcomes. Interruption of calcium signaling, a mechanism which can trigger CGRP release, has been suggested as one potential route by which exogenous food substances may impact CGRP secretion. The objective of this study was to investigate the effects of foods and a dietary supplement on two migraine related mechanisms in vitro: CGRP secretion from neuroendocrine CA77 cells, and calcium uptake by differentiated PC12 cells. Ginger and grape pomace extracts were selected for their anecdotal connections to reducing or promoting migraine. S-petasin was selected as a suspected active constituent of butterbur extract, the migraine prophylactic dietary supplement. Results showed a statistically significant decrease in stimulated CGRP secretion from CA77 cells following treatment with ginger (0.2 mg dry ginger equivalent/mL) and two doses of grape pomace (0.25 and 1.0 mg dry pomace equivalent/mL) extracts. Relative to vehicle control, CGRP secretion decreased by 22%, 43%, and 87%, respectively. S-petasin at 1.0 MUM also decreased CGRP secretion by 24%. Meanwhile, S-petasin and ginger extract showed inhibition of calcium influx, whereas grape pomace had no effect on calcium. These results suggest that grape pomace and ginger extracts, and S petasin may have anti-inflammatory propensity by preventing CGRP release in migraine, although potentially by different mechanisms, which future studies may elucidate further. PMID- 27376324 TI - The Emerging Role of Branched-Chain Amino Acids in Insulin Resistance and Metabolism. AB - Insulin is required for maintenance of glucose homeostasis. Despite the importance of insulin sensitivity to metabolic health, the mechanisms that induce insulin resistance remain unclear. Branched-chain amino acids (BCAAs) belong to the essential amino acids, which are both direct and indirect nutrient signals. Even though BCAAs have been reported to improve metabolic health, an increased BCAA plasma level is associated with a high risk of metabolic disorder and future insulin resistance, or type 2 diabetes mellitus (T2DM). The activation of mammalian target of rapamycin complex 1 (mTORC1) by BCAAs has been suggested to cause insulin resistance. In addition, defective BCAA oxidative metabolism might occur in obesity, leading to a further accumulation of BCAAs and toxic intermediates. This review provides the current understanding of the mechanism of BCAA-induced mTORC1 activation, as well as the effect of mTOR activation on metabolic health in terms of insulin sensitivity. Furthermore, the effects of impaired BCAA metabolism will be discussed in detail. PMID- 27376325 TI - Therapeutic Effectiveness of Anticancer Phytochemicals on Cancer Stem Cells. AB - Understanding how to target cancer stem cells (CSCs) may provide helpful insights for the development of therapeutic or preventive strategies against cancers. Dietary phytochemicals with anticancer properties are promising candidates and have selective impact on CSCs. This review summarizes the influence of phytochemicals on heterogeneous cancer cell populations as well as on specific targeting of CSCs. PMID- 27376326 TI - Biofilm-Forming Methicillin-Resistant Staphylococcus aureus Survive in Kupffer Cells and Exhibit High Virulence in Mice. AB - Although Staphylococcus aureus is part of the normal body flora, heavy usage of antibiotics has resulted in the emergence of methicillin-resistant strains (MRSA). MRSA can form biofilms and cause indwelling foreign body infections, bacteremia, soft tissue infections, endocarditis, and osteomyelitis. Using an in vitro assay, we screened 173 clinical blood isolates of MRSA and selected 20 high biofilm formers (H-BF) and low-biofilm formers (L-BF). These were intravenously administered to mice and the general condition of mice, the distribution of bacteria, and biofilm in the liver, lung, spleen, and kidney were investigated. MRSA count was the highest in the liver, especially within Kupffer cells, which were positive for acid polysaccharides that are associated with intracellular biofilm. After 24 h, the general condition of the mice worsened significantly in the H-BF group. In the liver, bacterial deposition and aggregation and the biofilm-forming spot number were all significantly greater for H-BF group than for L-BF. CFU analysis revealed that bacteria in the H-BF group survived for long periods in the liver. These results indicate that the biofilm-forming ability of MRSA is a crucial factor for intracellular persistence, which could lead to chronic infections. PMID- 27376328 TI - Tumor Targeting and Drug Delivery by Anthrax Toxin. AB - Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor binding component of the toxin, protective antigen, needs to be cleaved by furin like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associated proteases. This initial idea of re-targeting anthrax toxin to tumor cells was further elaborated in recent years and resulted in the design of many modifications of anthrax toxin, which resulted in successful tumor therapy in animal models. These modifications include the combination of different toxin variants that require activation by two different tumor associated proteases for increased specificity of toxin activation. The anthrax toxin system has proved to be a versatile system for drug delivery of several enzymatic moieties into cells. This highly efficient delivery system has recently been further modified by introducing ubiquitin as a cytosolic cleavage site into lethal factor fusion proteins. This review article describes the latest developments in this field of tumor targeting and drug delivery. PMID- 27376327 TI - Augmenting the Efficacy of Immunotoxins and Other Targeted Protein Toxins by Endosomal Escape Enhancers. AB - The toxic moiety of almost all protein-based targeted toxins must enter the cytosol of the target cell to mediate its fatal effect. Although more than 500 targeted toxins have been investigated in the past decades, no antibody-targeted protein toxin has been approved for tumor therapeutic applications by the authorities to date. Missing efficacy can be attributed in many cases to insufficient endosomal escape and therefore subsequent lysosomal degradation of the endocytosed toxins. To overcome this drawback, many strategies have been described to weaken the membrane integrity of endosomes. This comprises the use of lysosomotropic amines, carboxylic ionophores, calcium channel antagonists, various cell-penetrating peptides of viral, bacterial, plant, animal, human and synthetic origin, other organic molecules and light-induced techniques. Although the efficacy of the targeted toxins was typically augmented in cell culture hundred or thousand fold, in exceptional cases more than million fold, the combination of several substances harbors new problems including additional side effects, loss of target specificity, difficulties to determine the therapeutic window and cell type-dependent variations. This review critically scrutinizes the chances and challenges of endosomal escape enhancers and their potential role in future developments. PMID- 27376329 TI - Characterization of the Deep-Sea Streptomyces sp. SCSIO 02999 Derived VapC/VapB Toxin-Antitoxin System in Escherichia coli. AB - Toxin-antitoxin (TA) systems are small genetic elements that are ubiquitous in prokaryotes. Most studies on TA systems have focused on commensal and pathogenic bacteria; yet very few studies have focused on TAs in marine bacteria, especially those isolated from a deep sea environment. Here, we characterized a type II VapC/VapB TA system from the deep-sea derived Streptomyces sp. SCSIO 02999. The VapC (virulence-associated protein) protein belongs to the PIN (PilT N-terminal) superfamily. Overproduction of VapC strongly inhibited cell growth and resulted in a bleb-containing morphology in E. coli. The toxicity of VapC was neutralized through direct protein-protein interaction by a small protein antitoxin VapB encoded by a neighboring gene. Antitoxin VapB alone or the VapB/VapC complex negatively regulated the vapBC promoter activity. We further revealed that three conserved Asp residues in the PIN domain were essential for the toxic effect of VapC. Additionally, the VapC/VapB TA system stabilized plasmid in E. coli. Furthermore, VapC cross-activated transcription of several TA operons via a partially Lon-dependent mechanism in E. coli, and the activated toxins accumulated more preferentially than their antitoxin partners. Collectively, we identified and characterized a new deep sea TA system in the deep sea Streptomyces sp. and demonstrated that the VapC toxin in this system can cross activate TA operons in E. coli. PMID- 27376330 TI - Botulinum Toxin A for Bladder Pain Syndrome/Interstitial Cystitis. AB - Botulinum neurotoxin A (BoNT-A), derived from Clostridium botulinum, has been used clinically for several diseases or syndrome including chronic migraine, spasticity, focal dystonia and other neuropathic pain. Chronic pelvic or bladder pain is the one of the core symptoms of bladder pain syndrome/interstitial cystitis (BPS/IC). However, in the field of urology, chronic bladder or pelvic pain is often difficult to eradicate by oral medications or bladder instillation therapy. We are looking for new treatment modality to improve bladder pain or associated urinary symptoms such as frequency and urgency for patients with BPS/IC. Recent studies investigating the mechanism of the antinociceptive effects of BoNT A suggest that it can inhibit the release of peripheral neurotransmitters and inflammatory mediators from sensory nerves. In this review, we will examine the evidence supporting the use of BoNTs in bladder pain from basic science models and review the clinical studies on therapeutic applications of BoNT for BPS/IC. PMID- 27376331 TI - Relationship between VacA Toxin and Host Cell Autophagy in Helicobacter pylori Infection of the Human Stomach: A Few Answers, Many Questions. AB - Helicobacter pylori is a Gram-negative bacterium that colonizes the stomach of about half the global population and represents the greatest risk factor for gastric malignancy. The relevance of H. pylori for gastric cancer development is equivalent to that of tobacco smoking for lung cancer. VacA toxin seems to play a pivotal role in the overall strategy of H. pylori towards achieving persistent gastric colonization. This strategy appears to involve the modulation of host cell autophagy. After an overview of autophagy and its role in infection and carcinogenesis, I critically review current knowledge about the action of VacA on host cell autophagy during H. pylori infection of the human stomach. Although VacA is a key player in modulation of H. pylori-induced autophagy, a few discrepancies in the data are also evident and many questions remain to be answered. We are thus still far from a definitive understanding of the molecular mechanisms through which VacA affects autophagy and the consequences of this toxin action on the overall pathogenic activity of H. pylori. PMID- 27376332 TI - Getting Ready for the Dance: FANCJ Irons Out DNA Wrinkles. AB - Mounting evidence indicates that alternate DNA structures, which deviate from normal double helical DNA, form in vivo and influence cellular processes such as replication and transcription. However, our understanding of how the cellular machinery deals with unusual DNA structures such as G-quadruplexes (G4), triplexes, or hairpins is only beginning to emerge. New advances in the field implicate a direct role of the Fanconi Anemia Group J (FANCJ) helicase, which is linked to a hereditary chromosomal instability disorder and important for cancer suppression, in replication past unusual DNA obstacles. This work sets the stage for significant progress in dissecting the molecular mechanisms whereby replication perturbation by abnormal DNA structures leads to genomic instability. In this review, we focus on FANCJ and its role to enable efficient DNA replication when the fork encounters vastly abundant naturally occurring DNA obstacles, which may have implications for targeting rapidly dividing cancer cells. PMID- 27376333 TI - Collision of Trapped Topoisomerase 2 with Transcription and Replication: Generation and Repair of DNA Double-Strand Breaks with 5' Adducts. AB - Topoisomerase 2 (Top2) is an essential enzyme responsible for manipulating DNA topology during replication, transcription, chromosome organization and chromosome segregation. It acts by nicking both strands of DNA and then passes another DNA molecule through the break. The 5' end of each nick is covalently linked to the tyrosine in the active center of each of the two subunits of Top2 (Top2cc). In this configuration, the two sides of the nicked DNA are held together by the strong protein-protein interactions between the two subunits of Top2, allowing the nicks to be faithfully resealed in situ. Top2ccs are normally transient, but can be trapped by cancer drugs, such as etoposide, and subsequently processed into DSBs in cells. If not properly repaired, these DSBs would lead to genome instability and cell death. Here, I review the current understanding of the mechanisms by which DSBs are induced by etoposide, the unique features of such DSBs and how they are repaired. Implications for the improvement of cancer therapy will be discussed. PMID- 27376335 TI - Estimation of Median Lethal Concentration of Three Isolates of Beauveria bassiana for Control of Megacopta cribraria (Heteroptera: Plataspidae) Bioassayed on Solid Lygus spp. Diet. AB - The kudzu bug, Megacopta cribraria (F.), is an urban nuisance and significant agricultural pest. The median lethal concentrations of three strains of Beauveria bassiana (Balsamo), including the Mississippi Delta native strain (NI8) isolated from Lygus lineolaris (Palisot de Beauvois), the commercial strain BotaniGard((r)) (GHA) (Victor, NY, USA), and the B. bassiana strain isolated from M. cribraria (KUDSC), were estimated on kudzu bug adults. A technique developed to evaluate B. bassiana against L. lineolaris was used. Younger adults (eight days after collection) were treated with NI8 and GHA and older adult (50 days after collection) were treated with NI8, GHA and KUDSC. Higher concentrations (n * 106, n * 107) of NI8 and GHA caused kudzu bug mortality two days after treatment in younger adults and similar concentrations of NI8, GHA, and KUDSC caused mortality one day after treatment in older adults. Lower concentrations (n * 104, n * 105) were not significantly different in mortality between strains. LS50 values of the KUDSC were significantly lower than NI8 and GHA values in older adults. This is the first available information on median lethal concentration of B. bassiana on kudzu bug adults bioassayed on artificial diet. It was determined that B. bassiana (KUDSC and NI8) are highly effective for young adults at very low doses (LC50 1.98-4.98 viable spores per mm2). PMID- 27376334 TI - The Cosmic Zoo: The (Near) Inevitability of the Evolution of Complex, Macroscopic Life. AB - Life on Earth provides a unique biological record from single-cell microbes to technologically intelligent life forms. Our evolution is marked by several major steps or innovations along a path of increasing complexity from microbes to space faring humans. Here we identify various major key innovations, and use an analytical toolset consisting of a set of models to analyse how likely each key innovation is to occur. Our conclusion is that once the origin of life is accomplished, most of the key innovations can occur rather readily. The conclusion for other worlds is that if the origin of life can occur rather easily, we should live in a cosmic zoo, as the innovations necessary to lead to complex life will occur with high probability given sufficient time and habitat. On the other hand, if the origin of life is rare, then we might live in a rather empty universe. PMID- 27376336 TI - Simultaneous Quantification and Differentiation of Streptococcus suis Serotypes 2 and 9 by Quantitative Real-Time PCR, Evaluated in Tonsillar and Nasal Samples of Pigs. AB - Invasive Streptococcus suis (S. suis) infections in pigs are often associated with serotypes 2 and 9. Mucosal sites of healthy pigs can be colonized with these serotypes, often multiple serotypes per pig. To unravel the contribution of these serotypes in pathogenesis and epidemiology, simultaneous quantification of serotypes is needed. A quantitative real-time PCR (qPCR) targeting cps2J (serotypes 2 and 1/2) and cps9H (serotype 9) was evaluated with nasal and tonsillar samples from S. suis exposed pigs. qPCR specifically detected serotypes in all pig samples. The serotypes loads in pig samples estimated by qPCR showed, except for serotype 9 in tonsillar samples (correlation coefficient = 0.25), moderate to strong correlation with loads detected by culture (correlation coefficient > 0.65), and also in pigs exposed to both serotypes (correlation coefficient > 0.75). This qPCR is suitable for simultaneous differentiation and quantification of important S. suis serotypes. PMID- 27376337 TI - Efficiently Combining Water Reuse and Desalination through Forward Osmosis Reverse Osmosis (FO-RO) Hybrids: A Critical Review. AB - Forward osmosis (FO) is a promising membrane technology to combine seawater desalination and water reuse. More specifically, in a FO-reverse osmosis (RO) hybrid process, high quality water recovered from the wastewater stream is used to dilute seawater before RO treatment. As such, lower desalination energy needs and/or water augmentation can be obtained while delivering safe water for direct potable reuse thanks to the double dense membrane barrier protection. Typically, FO-RO hybrid can be a credible alternative to new desalination facilities or to implementation of stand-alone water reuse schemes. However, apart from the societal (public perception of water reuse for potable application) and water management challenges (proximity of wastewater and desalination plants), FO-RO hybrid has to overcome technical limitation such as low FO permeation flux to become economically attractive. Recent developments (i.e., improved FO membranes, use of pressure assisted osmosis, PAO) demonstrated significant improvement in water flux. However, flux improvement is associated with drawbacks, such as increased fouling behaviour, lower rejection of trace organic compounds (TrOCs) in PAO operation, and limitation in FO membrane mechanical resistance, which need to be better considered. To support successful implementation of FO-RO hybrid in the industry, further work is required regarding up-scaling to apprehend full scale challenges in term of mass transfer limitation, pressure drop, fouling and cleaning strategies on a module scale. In addition, refined economics assessment is expected to integrate fouling and other maintenance costs/savings of the FO/PAO-RO hybrid systems, as well as cost savings from any treatment step avoided in the water recycling. PMID- 27376338 TI - Development of Formaldehyde Biosensor for Determination of Formalin in Fish Samples; Malabar Red Snapper (Lutjanus malabaricus) and Longtail Tuna (Thunnus tonggol). AB - Electrochemical biosensors are widely recognized in biosensing devices due to the fact that gives a direct, reliable, and reproducible measurement within a short period. During bio-interaction process and the generation of electrons, it produces electrochemical signals which can be measured using an electrochemical detector. A formaldehyde biosensor was successfully developed by depositing an ionic liquid (IL) (e.g., 1-ethyl-3-methylimidazolium trifluoromethanesulfonate ([EMIM][Otf])), gold nanoparticles (AuNPs), and chitosan (CHIT), onto a glassy carbon electrode (GCE). The developed formaldehyde biosensor was analyzed for sensitivity, reproducibility, storage stability, and detection limits. Methylene blue was used as a redox indicator for increasing the electron transfer in the electrochemical cell. The developed biosensor measured the NADH electron from the NAD+ reduction at a potential of 0.4 V. Under optimal conditions, the differential pulse voltammetry (DPV) method detected a wider linear range of formaldehyde concentrations from 0.01 to 10 ppm within 5 s, with a detection limit of 0.1 ppm. The proposed method was successfully detected with the presence of formalin in fish samples, Lutjanus malabaricus and Thunnus Tonggol. The proposed method is a simple, rapid, and highly accurate, compared to the existing technique. PMID- 27376339 TI - Impedimetric Label-Free Immunosensor on Disposable Modified Screen-Printed Electrodes for Ochratoxin A. AB - An impedimetric label-free immunosensor on disposable screen-printed carbon electrodes (SPCE) for quantitative determination of Ochratoxin A (OTA) has been developed. After modification of the SPCE surface with gold nanoparticles (AuNPs), the anti-OTA was immobilized on the working electrode through a cysteamine layer. After each coating step, the modified surfaces were characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The capacitance was chosen as the best parameter that describes the reproducible change in electrical properties of the electrode surface at different OTA concentrations and it was used to investigate the analytical parameters of the developed immunosensor. Under optimized conditions, the immunosensor showed a linear relationship between 0.3 and 20 ng/mL with a low detection limit of 0.25 ng/mL, making it suitable to control OTA content in many common food products. Lastly, the immunosensor was used to measure OTA in red wine samples and the results were compared with those registered with a competitive ELISA kit. The immunosensor was sensitive to OTA lower than 2 MUg/kg, which represents the lower acceptable limit of OTA established by European legislation for common food products. PMID- 27376340 TI - Variations in the Life Cycle of Anemone patens L. (Ranunculaceae) in Wild Populations of Canada. AB - Based on a study of a perennial herb Anemone patens L. (Ranunculaceae) in a variety of natural habitats in Saskatchewan, Canada, eight life stages (seed, seedling, juvenile, immature, vegetative, generative, subsenile, and senile) are distinguished and characterized in detail. The species ontogenetic growth patterns are investigated. A. patens has a long life cycle that may last for several decades which leads to the formation of compact clumps. The distribution and age of clumps vary substantially in different environments with different levels of disturbance. The plant ontogeny includes the regular cycle with reproduction occurring through seeds. There is an optional subsenile vegetative disintegration at the end of the life span. The following variations in the life cycle of A. patens are identified: with slower development in young age, with an accelerated development, with omission of the generative stage, with retrogression to previous life stages in mature age, and with vegetative dormancy. The range of variations in the life cycle of A. patens may play an important role in maintaining population stability in different environmental conditions and management regimes. PMID- 27376341 TI - The tripeptide KdPT ameliorates ongoing psoriasis-like skin inflammation in murine and human skin. AB - Psoriasis is a chronic inflammatory disease appearing as scaly erythematous cutaneous lesions, which are characterized by parakeratosis and acanthosis as well as the infiltration of immune cells, such as T helper-1 and T helper-17 cells. Here, we demonstrated that KdPT, a tripeptide structurally related to the C-terminal amino acids of alpha-melanocyte-stimulating hormone, which was previously shown to exhibit anti-inflammatory effects in intestinal inflammation, ameliorated ongoing disease in the mouse model of imiquimod-induced psoriasis like skin inflammation and in the small xenotransplant mouse model of psoriasis. We could show that systemic KdPT treatment significantly reduced hyperkeratosis and acanthosis in murine as well as human skin. Moreover, KdPT upregulated Foxp3 in CD4+ T cells from mice and from peripheral blood of individuals with psoriasis and decreased the expression of type 1 inflammatory cytokines, indicating that the beneficial effect of KdPT was, at least in part, mediated by the induction of functional regulatory T cells that suppressed the activation of pathogenic CD4+ IFN-gamma+ and CD4+ IL-17+ T cells. Thus, these data might suggest KdPT as a potential novel therapeutic alternative for the treatment of psoriasis. PMID- 27376346 TI - Circulating Cell-Free Unmethylated DNA as a Marker of Graft Dysfunction in Pancreas Transplantation. PMID- 27376347 TI - Assessing Fidelity of a Community-Based Opioid Overdose Prevention Program: Modification of the Fidelity Checklist. AB - BACKGROUND: The evaluation and maintenance of treatment fidelity is an important methodological consideration in intervention research. Treatment fidelity is the degree to which interventions are delivered as outlined by the program developers. A lack of fidelity to the intervention model has the potential to be a large source of error, including type I and type II error. Monitoring and assuring fidelity is critical to assuring the validity of the interventions. The Fidelity Checklist is a reliable and valid tool designed to measure fidelity in a group-based parenting program. The Fidelity Checklist assesses group leaders' maintenance of the intervention protocol (adherence) and their group facilitation and process skills (competence). OBJECTIVES: The purpose of this article is to describe the systematic process of modifying the Fidelity Checklist for use in a community-based opioid overdose prevention group educational intervention. METHODS: A biphasic approach was used to modify the Fidelity Checklist. Phase 1 included engaging key stakeholders during a full-day meeting to determine adherence subscale components. Phase 2 included: (a) the modification of the competence subscale of the Fidelity Checklist, (b) adaptation of the coding manual defining the components of the Fidelity Checklist, and (c) creating a fidelity checklist to guide interventionists. RESULTS: The biphasic systematic modification approach resulted in a revised Fidelity Checklist that was successfully used to measure treatment fidelity in a community-based opioid overdose prevention program. CLINICAL RELEVANCE: The findings of this study provide information for nurse researchers and nurse educators for modifying a fidelity checklist that can be used to enhance community-based educational interventions. PMID- 27376348 TI - Nanosilver inhibits nitrification and reduces ammonia-oxidising bacterial but not archaeal amoA gene abundance in estuarine sediments. AB - Silver nanoparticles (AgNPs) enter estuaries via wastewater treatment effluents, where they can inhibit microorganisms, because of their antimicrobial properties. Ammonia-oxidising bacteria (AOB) and archaea (AOA) are involved in the first step of nitrification and are important to ecosystem function, especially where effluent discharge results in high nitrogen inputs. Here, we investigated the effect of a pulse addition of AgNPs on AOB and AOA ammonia monooxygenase (amoA) gene abundances and benthic nitrification potential rates (NPR) in low-salinity and mesohaline estuarine sediments. Whilst exposure to 0.5 mg L-1 AgNPs had no significant effect on amoA gene abundances or NPR, 50 mg L-1 AgNPs significantly decreased AOB amoA gene abundance (up to 76% over 14 days), and significantly decreased NPR by 20-fold in low-salinity sediments and by twofold in mesohaline sediments, after one day. AgNP behaviour differed between sites, whereby greater aggregation occurred in mesohaline waters (possibly due to higher salinity), which may have reduced toxicity. In conclusion, AgNPs have the potential to reduce ammonia oxidation in estuarine sediments, particularly where AgNPs accumulate over time and reach high concentrations. This could lead to long-term risks to nitrification, especially in polyhaline estuaries where ammonia oxidation is largely driven by AOB. PMID- 27376349 TI - Variability in Saponin Content, Cancer Antiproliferative Activity and Physicochemical Properties of Concentrated Agave Sap. AB - Concentrated agave sap (CAS) has gained popularity as an unrefined sweetener. It is obtained by boiling "aguamiel" that contains phytochemicals with diverse bioactivities. Saponins have been the most widely studied agave phytochemicals due to their cancer antiproliferative effect but their concentration may vary due to maturity of the agave plant and collection site. In this study, 18 CAS samples produced in different states of Mexico were analyzed using multivariate methods to determine which physicochemical or phytochemical parameters were responsible for variation. Additionally, extracts with different saponin profiles were tested to determine possible correlations with antiproliferative activity. Total soluble solids, pH, and water activity were similar to those reported for other agave sweeteners. Antioxidant capacity of samples was correlated to browning index. Eleven steroidal saponins were found in CAS samples and they were the main source of variability. Magueyoside B, a kammogenin tetraglycoside, was the most abundant saponin in all samples. With respect to bioactivity, multivariate analysis indicated that magueyoside B and a gentrogenin tetraglycoside were compounds strongly related with bioactivity. CAS from Hidalgo, Puebla, and Veracruz had higher concentration of magueyoside B than from the other kamogenin tetraglycoside found in the samples from other Mexican states. These results could be used as a first approach to characterize and standardize CAS to validate the potential health benefits derived from its consumption. PMID- 27376350 TI - Graphene oxide alleviates the ecotoxicity of copper on the freshwater microalga Scenedesmus obliquus. AB - The extensive industrial application of graphene oxide (GO), has increased its exposure risk to various aquatic organisms and its potential to affect the toxicity of other environmental pollutants. In this study, we investigated the combined toxicity of GO and copper on the freshwater microalga Scenedesmus obliquus, using the MIXTOX model. The effects of low concentration (1mg/L) exposure to GO were investigated with environmentally relevant concentrations of copper by using a 12-d subacute toxicity test, with pre- and post-GO treatment. Results showed that there were significant antagonistic effects between GO and copper on S. obliquus, and GO was found to reduce ecotoxicity of copper even at low and environmentally relevant concentrations (1mg/L). PMID- 27376351 TI - Effects of multigenerational exposure to elevated temperature on reproduction, oxidative stress, and Cu toxicity in Daphnia magna. AB - This study evaluated the effect of temperature (20 and 25 degrees C) on reproduction, oxidative stress, and copper (Cu) toxicity in Daphnia magna across three generations (F0, F1, and F2). Exposing D. magna to elevated temperature significantly decreased the number of offspring per female per day, the time to first brood, and body length compared to exposure to the optimal temperature (p<0.05). In addition, elevated temperature induced a significantly higher production of reactive oxygen species and lipid peroxidation (p<0.05). These findings suggest that D. magna likely responded to thermal stress by investing more energy into defense mechanisms, rather than growth and reproduction. In addition, oxidative stress at the elevated temperature gradually increased with each generation, possibly owing to the reduced fitness of the offspring. Exposing D. magna to 25 degrees C (EC50=34+/-3ugL(-1)) substantially increased the median effective concentration of Cu in all generations compared to exposure to 20 degrees C (EC50=25+/-3ugL(-1)), indicating a decrease in acute toxicity at elevated temperature. However, elevated temperature significantly increased the oxidative stress induced by a sublethal concentration of Cu (10ugL(-1)). The interaction between elevated temperature and Cu exposure appears to be synergistic; however, this needs to be confirmed using multiple generations in a long-term experiment. PMID- 27376352 TI - Graphene oxide induces plasma membrane damage, reactive oxygen species accumulation and fatty acid profiles change in Pichia pastoris. AB - During the past couple of years, graphene nanomaterials were extremely popular among the scientists due to the promising properties in many aspects. Before the materials being well applied, we should first focus on their biosafety and toxicity. In this study, we investigated the toxicity of synthesized graphene oxide (GO) against the model industrial organism Pichia pastoris. We found that the synthesized GO showed dose-dependent toxicity to P. pastoris, through cell membrane damage and intracellular reactive oxygen species (ROS) accumulation. In response to these cell stresses, cells had normal unsaturated fatty acid (UFA) levels but increased contents of polyunsaturated fatty acid (PUFA) with up regulation of UFA synthesis-related genes on the transcriptional level, which made it overcome the stress under GO attack. Two UFA defective strains (spt23Delta and fad12Delta) were used to demonstrate the results above. Hence, this study suggested a close connection between PUFAs and cell survival against GO. PMID- 27376353 TI - Secondary biomarkers of insecticide-induced stress of honey bee colonies and their relevance for overwintering strength. AB - The evaluation of pesticide side-effects on honeybees is hampered by a lack of colony-level bioassays that not only are sensitive to physiological changes, but also allow predictions about the consequences of exposure for longer-term colony productivity and survival. Here we measured 28 biometrical, biochemical and behavioural indicators in a field study with 63 colonies and 3 apiaries. Colonies were stressed in early summer by feeding them for five days with either the carbamate growth regulator fenoxycarb or the neurotoxic neonicotinoid imidacloprid, or left untreated. Candidate stress indicators were measured 8-64 days later. We determined which of the indicators were influenced by the treatments, and which could be used as predictors in regression analyses of overwintering strength. Among the indicators influenced by fenoxycarb were the amount of brood in colonies as well as the learning performance and 24h-memory of bees, and the concentration of the brood food component 10HDA in head extracts. Imidacloprid significantly affected honey production, total number of bees and activity of the immune-related enzyme phenoloxidase in forager bee extracts. Indicators predictive of overwintering strength but unrelated to insecticide feeding included vitellogenin titer and glucose oxidase-activity in haemolymph/whole body-extracts of hive bees. Apart from variables that were themselves components of colony strength (numbers of bees/brood cells), the only indicator that was both influenced by an insecticide and predictive of overwintering strength was the concentration of 10HDA in worker bee heads. Our results show that physiological and biochemical bioassays can be used to study effects of insecticides at the colony level and assess the vitality of bee colonies. At the same time, most bioassays evaluated here appear of limited use for predicting pesticide effects on colony overwintering strength, because those that were sensitive to the insecticides were not identical with those that were predictive of colony overwintering. Our study therefore illustrates the difficulties involved in evaluating the economic/ecological significance of pesticide-induced stress in honey bee field studies. PMID- 27376354 TI - The ceramide inhibitor fumonisin B1 mitigates the pulmonary effects of low-dose diesel exhaust inhalation in mice. AB - Recent studies have suggested that inhalation of diesel exhaust (DE), a major source of air pollution, results in pulmonary alterations; however, the effects of DE at low concentrations are poorly understood. Therefore, this study was conducted to elucidate the pulmonary effects of low-level exposure to DE and the potential role of a ceramide de novo biosynthesis inhibitor, fumonisin B1 (FB1) to ameliorate the DE-toxicity. Male C57BL/6J mice underwent 1- or 7-day experiments (4 equal groups/experiment) and were assigned to the control, DE (0.1mg/m(3)), FB1 (6.75mg/kg body weight SC at days 0, 3 and 6) or DE+FB1 groups. DE and/or FB1 treatment had no effect on the expression of Nos2, a biomarker of oxidative stress. Ceramide production in the bronchial epithelial cells and Sphk1 mRNA expression were induced in the lung after the 7-day DE exposure and were partially suppressed by the FB1 treatment. Additionally, the effects of DE on SP A and SP-D mRNA expression were also suppressed by the FB1 treatment. These results suggest that ceramide and Sphk1 may be sensitive biomarkers for low-level DE-induced pulmonary effects. Collectively, ceramide likely contributes to the DE induced early stage of airway inflammation, which is considered a potential pulmonary target during low-level DE exposure. PMID- 27376356 TI - Erratum to: Association of cardiovascular disease risk factors with left ventricular mass, biventricular function, and the presence of silent myocardial infarction on cardiac MRI in an asymptomatic population. PMID- 27376355 TI - Protein intake during pregnancy and offspring body composition at 6 years: the Generation R Study. AB - PURPOSE: Intra-uterine exposure to protein may affect body composition and may increase the prevalence of childhood adiposity. Therefore, we examined whether protein intake during pregnancy is associated with offspring body composition at the age of 6 years and whether associations differ for animal protein and vegetable protein. METHODS: We included 2694 Dutch mother-child pairs participating in a prospective population-based cohort in Rotterdam, the Netherlands. Energy-adjusted protein was measured in pregnancy using a food frequency questionnaire and analyzed in quartiles. At a mean age of 6.1 +/- 0.4 years, we measured children's body mass index, and fat-free mass index and fat mass index using dual-energy X-ray absorptiometry. Outcomes were standardized for age and sex. BMI was used to classify children's overweight status. RESULTS: After adjustment for sociodemographic and lifestyle factors, a higher maternal protein intake was associated with a higher children's fat-free mass index [difference 0.14 standard deviation (95 % CI 0.03, 0.25) for highest vs. lowest quartile of protein intake], but not with children's fat mass index or body mass index. Comparable associations were found for animal protein and vegetable protein. Maternal protein intake was not associated with children's overweight. CONCLUSIONS AND RELEVANCE: This study suggests that higher protein intake during pregnancy is associated with a higher fat-free mass in children at the age of 6 years, but not with their fat mass. Our results do not suggest specific recommendations regarding maternal protein intake during pregnancy to prevent overweight in the offspring. PMID- 27376357 TI - Real-time analysis of the polymerization kinetics of 1,4-butanediol and 4,4' diphenylmethanediisocyanate by fiber-coupled Fourier transform infrared spectroscopy. AB - Polyurethanes are a polymer class with large property diversity. However, despite their extreme technical importance, only few research data regarding the on-line analysis and the derivation of kinetic polymerization data are available in the literature. The present work focuses on the in-line monitoring of the solution polymerization of 4,4'-diphenylmethanediisocyanate and 1,4-butanediol by fiber coupled FT-IR spectroscopy in the attenuated total reflection (ATR) mode at variable temperatures and the interpretation of the spectral changes as a function of polymerization progress. Furthermore, the activation energy of the solution polymerization will be derived from the kinetic data and experimental issues of the ATR in-line measurement mode will be addressed. PMID- 27376358 TI - Propagation of measurement accuracy to biomass soft-sensor estimation and control quality. AB - In biopharmaceutical process development and manufacturing, the online measurement of biomass and derived specific turnover rates is a central task to physiologically monitor and control the process. However, hard-type sensors such as dielectric spectroscopy, broth fluorescence, or permittivity measurement harbor various disadvantages. Therefore, soft-sensors, which use measurements of the off-gas stream and substrate feed to reconcile turnover rates and provide an online estimate of the biomass formation, are smart alternatives. For the reconciliation procedure, mass and energy balances are used together with accuracy estimations of measured conversion rates, which were so far arbitrarily chosen and static over the entire process. In this contribution, we present a novel strategy within the soft-sensor framework (named adaptive soft-sensor) to propagate uncertainties from measurements to conversion rates and demonstrate the benefits: For industrially relevant conditions, hereby the error of the resulting estimated biomass formation rate and specific substrate consumption rate could be decreased by 43 and 64 %, respectively, compared to traditional soft-sensor approaches. Moreover, we present a generic workflow to determine the required raw signal accuracy to obtain predefined accuracies of soft-sensor estimations. Thereby, appropriate measurement devices and maintenance intervals can be selected. Furthermore, using this workflow, we demonstrate that the estimation accuracy of the soft-sensor can be additionally and substantially increased. PMID- 27376360 TI - Mixed Polymer-Coated Magnetic Nanoparticles as Forward Osmosis Draw Agents of Tuned Hydrophilicity. AB - We recently reported a polymer-coated magnetic nanoparticle (MNP) draw agent for the forward osmosis (FO) water desalination process. The water flux was found to increase when the polymer poly(sodium acrylate) (PSA) was anchored to the MNP surface as compared to the polymer (or polyelectrolyte solution) alone, due to the polymer chains being stretched out and most of the hydrophilic groups on the polymer contributing to water flux. We herein report the use of a secondary polymer poly(N-isopropylacrylamide) PNIPAM to manipulate the PSA polymer conformation and influence inter- and intrachain interactions to enhance the efficiency of the FO draw agent. These PSA-PNIPAM-coated MNPs generated a much higher water flux of ~11.66 LMH when compared to the 100 % PSA-coated MNPs featuring a value of ~5.32 LMH under identical FO conditions. The osmotic pressure and water flux driven by the mixed polymer-coated MNPs were found to be a strong function of the net polymer coverage on MNPs, that is, net available hydrophilic groups. Our new draw agent demonstrates potential for use in the water industry due to its improved efficiency and cost effectiveness as it uses only ~0.062 % (w/v) of the draw agent solution. PMID- 27376359 TI - [Focal dose escalation in the treatment of prostate cancer : Long-term results of HDR brachytherapy]. AB - BACKGROUND: We prospectively examined the effect and the safety of intensity modulated HDR brachytherapy (IMBT) with focal dose escalation. MATERIALS AND METHODS: A total of 139 patients undergoing primary therapy for prostate cancer and 11 patients with recurrence were included. Data analysis focused on the following factors: date of primary diagnosis, Gleason score, initial prostate specific antigen (PSA) value, PSA nadir, volume of the prostate in the transrectal ultrasound, biopsy of the prostate gland, androgen deprivation, chemotherapy, uroflowmetry, pre- and postoperative post-void residual urine (PVR), number of the needles in the prostate lobes and analysis of follow-up data. RESULTS: In the primary therapy group, 87.6 % of the patients had a PSA of 0-4 ng/ml at the time of follow-up, while in the recurrence group 81.8 % of patients were within this range. Overall, 55.8 % of patients in the primary group had a PSA nadir under 0.1 ng/ml, 37.2 % under 1 ng/ml, 5.8 % under 5 ng/ml and 1.2 % (1 patient) over 5 ng/ml. In the recurrence group, 100 % had a PSA nadir under 0.1 ng/dl. Fifty patients of the primary group reported grade 1 toxicity (Common Toxicity Criteria): 29 localized to the bladder and 21 to the rectum. Seventeen patients had grade 2 toxicity of the bladder and 1 patient had grade 3 toxicity of the bladder. Finally there was one grade 4 toxicity due to perforation of the sigmoid colon. In the recurrence group, 3 patients with grade 1 toxicity were observed (2 bladder and 1 bowl). Also 3 patients had grade 2 toxicity of the bladder, 1 patient had a grade 3 bladder toxicity and 1 patient had grade 4 toxicity due to bowl fistula. There were no grade 5 toxicities. CONCLUSION: The modifications of the "Kiel method" with focal dose escalation was proven as effective in locally advanced prostate carcinoma and in local recurrences of the disease with low level toxicity. PMID- 27376361 TI - Prognostic value of CALR vs. JAK2V617F mutations on splenomegaly, leukemic transformation, thrombosis, and overall survival in patients with primary fibrosis: a meta-analysis. AB - The understanding of genetic basis for Philadelphia-negative myeloproliferative neoplasm (MPN) has got much progress in recent years. But the effect of CALR vs. JAK2V617F mutations on the clinical progression and prognosis of primary fibrosis (PMF) remains relatively obscure. In this meta-analysis, we searched Pubmed, Embase, and Web of Science databases for observational studies published until February 2016. Researches that evaluated CALR vs. JAK2V617F mutations on PMF relevant complications (splenomegaly, leukemic transformation, or thrombosis) and overall survival were selected. Pooled adjust odds ratio (OR), hazard risk (HR), and the corresponding 95 % confidence intervals (CI) were calculated for the CALR mutant versus the JAK2-mutant categories. Twelve studies involving 435 CALR mutated and 1116 JAK2V617F PMF patients were analyzed. CALR-mutated patients displayed a lower risk of splenomegaly (OR 0.47, 95 % CI 0.29-0.78) and thrombosis (OR 0.52, 95 % CI 0.29-0.92) but showed no significant difference in the risk of leukemic transformation (OR 0.90, 95 % CI 0.55-1.47) when compared with JAK2-mutated patients. CALR mutation favorably affected overall survival while JAK2 mutation led to poorer survival rate (HR 2.58, 95 % CI 2.08-3.20). This meta-analysis confirmed that a genetic classification of PMF by CALR and JAK2 mutations carried significant prognostic relevance. PMID- 27376362 TI - Impact of Fc gamma-receptor polymorphisms on the response to rituximab treatment in children and adolescents with mature B cell lymphoma/leukemia. AB - Recent studies in adult lymphoma patients have indicated a correlation between polymorphisms of Fc gamma-receptors (FcgammaRs, encoded by the respective FCGR genes) and the response to rituximab treatment. In vitro, cells expressing FcgammaRIIIa-158V mediate antibody-dependent cellular cytotoxicity (ADCC) more efficiently than cells expressing FcgammaRIIIa-158F. The impact of the FCGR2A 131HR polymorphism is unclear. In this study, the FCGR polymorphisms FCGR3A-158VF and FCGR2A-131HR were analyzed in pediatric patients with mature aggressive B cell non-Hodgkin lymphoma/leukemia (B-NHL). Pediatric patients received a single dose of rituximab monotherapy. Response was evaluated on day 5 followed by standard chemotherapy for B-NHL. Among 105 evaluable patients, a response to rituximab was observed in 21 % of those homozygous for FcgammaRIIa-131RR (5/24) compared to 48 % of patients who were HH and HR FcgammaRIIa-131 allele carriers (18/34 and 21/47, respectively; p = 0.044). Among patients with the FCGR3A-158 polymorphism, those homozygous for the FF genotype had a significantly favorable rituximab response rate of 59 % (22/37) compared to 32 % in patients who were FcgammaRIIIa-158VV and FcgammaRIIIa-VF allele carriers (2/9 and 20/59, respectively; p = 0.022). A stringent phase II response evaluation of children and adolescents with B-NHL after one dose of rituximab monotherapy showed a significant association between the rituximab response rate and FCGR polymorphisms. These findings support the hypothesis that FCGR polymorphisms represent patient-specific parameters that influence the response to rituximab. PMID- 27376363 TI - Outcome analysis of high-dose chemotherapy and autologous stem cell transplantation in adolescent and young adults with relapsed or refractory Hodgkin lymphoma. AB - High-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) can salvage many patients with relapsed or refractory Hodgkin's lymphoma (HL). We are reporting the outcome of HDC auto-SCT and the impact of 21 prognostic factors in relapsed and refractory adolescent (14-21 years) and young adult (>21-30 years) (AYA) HL patients. We used Fine and Gray's competing risk analysis method and regression model for outcome analysis. From 1996 to 2013, 290 consecutive patients with biopsy-proven HL underwent HDC auto-SCT for relapsed/refractory HL; 216 patients (74.5 %) were AYA at the time of auto-SCT. Male/female were equal, median age at auto-SCT was 22.4 years, and there were 94 adolescent (43.5 %) and 122 young adults (56.5 %). There was refractory disease in 121 (56 %) patients, relapsed in 95 (44 %). Median follow-up was 72.6 months. The Kaplan-Meier method estimated that 5-year overall survival is 62.7 % (adolescents (63.5 %), young adults (62 %)) and event-free survival was 51.3 %. Five-year cumulative incidence of disease-specific death (DS-death) is 33 % and that of DS-event is 45 %. For DS death, the multivariate analysis identified complete remission (CR) duration of <12 months (hazard ratio (HR) 3.61, P = 0.0009), no CR after salvage (HR: 3.93, P = 0.0002), and nodular sclerosis pathology (HR 3.3, P = 0.016) and positive B symptoms (HR 2, P = 0.028) as negative factors. For DS-event, CR duration of <12 months (HR 1.88, P = 0.02), no CR after salvage (HR 3.47, P = 0.000005) and nodular sclerosis pathology (HR 1.88, P = 0.02) were found significant. The Kaplan-Meier method estimated overall survival (OS) at 36 months with 0-2:3:4 factors being 93.6:54:21 %, respectively (P value <0.001). Kaplan-Meier estimated event-free survival (EFS) at 36 months with 0-1:2:3 factors being 84.6:65:31 %, respectively (P value <0.001). Clinically, adolescents have similar outcomes as young adults. PMID- 27376364 TI - The Sangre Por Salud Biobank: Facilitating Genetic Research in an Underrepresented Latino Community. AB - BACKGROUND/AIMS: The Sangre Por Salud (Blood for Health; SPS) Biobank was created for the purpose of expanding precision medicine research to include underrepresented Latino patients. It is the result of a unique collaboration between Mayo Clinic and Mountain Park Health Center, a federally qualified community health center in Phoenix, Arizona. This report describes the rationale, development, implementation, and characteristics of the SPS Biobank. METHODS: Latino adults (ages 18-85 years) who were active patients within Mountain Park Health Center's internal medicine practice in Phoenix, Ariz., and had no history of diabetes were eligible. Participants provided a personal and family history of chronic disease, completed a sociodemographic, psychosocial, and behavioral questionnaire, underwent a comprehensive cardiometabolic risk assessment (anthropometrics, blood pressure and labs), and provided blood samples for banking. Laboratory results of cardiometabolic testing were returned to the participants and their providers through the electronic health record. RESULTS: During the first 2 years of recruitment into the SPS Biobank, 2,335 patients were approached and 1,432 (61.3%) consented to participate; 1,354 (94.5%) ultimately completed all requisite questionnaires and medical evaluations. The cohort is primarily Spanish-speaking (72.9%), female (73.3%), with a mean age of 41.3 +/- 12.5 years. Most participants were born outside of the US (77.9%) and do not have health insurance (77.5%). The prevalence of overweight (35.5%) and obesity (45.0%) was high, as was previously unidentified prediabetes (55.9%), type 2 diabetes (7.4%), prehypertension (46.8%), and hypertension (16.2%). The majority of participants rated their health as good to excellent (72.1%) and, as a whole, described their overall quality of life as high (7.9/10). CONCLUSION: Collaborative efforts such as the SPS Biobank are critical for ensuring that underrepresented minority populations are included in precision medicine initiatives and biomedical research that seeks to improve human health and reduce the burdens of disease. PMID- 27376365 TI - UCP2 and PLIN1 Expression Affects the Resting Metabolic Rate and Weight Loss on Obese Patients. AB - BACKGROUND: Analysis of the expression of genes related to the energy metabolism can elucidate the understanding of physiological and genetic factors that contribute to obesity. This study aimed to evaluate the expression of genes and its influence on resting metabolic rate and weight loss in obese patients before and after bariatric surgery. METHODS: This study was conducted on 23 women, who were divided into two groups: bariatric surgery (preoperative and 6 months after surgery) and control. Abdominal subcutaneous adipose tissue samples were collected to analyze the gene expression, and the resting metabolic rate (RMR) was measured by indirect calorimetry. RESULTS: Significant differences were observed in weight reduction (22 %, p = 0.01), BMI (22.5 %, p = 0.01), and RMR values (10.5 %, p = 0.01) after the bariatric surgery, while the weight-adjusted RMR increased (15.8 %, p = 0.01). Increased UCP2 expression after 6 months of Roux-en-Y gastric bypass (RYGB) as compared to preoperative period (0.764 to 1.268, p = 0.01) was observed. Analysis with weight-adjusted RMR as dependent variable revealed that UCP2 (r 2 = 0.517, p = 0.01) and PLIN1 (r 2 = 0.420, p = 0.04) expression determine the RMR values in preoperative period. Moreover, UCP2 and PLIN1 expression in preoperative period influenced the percentage of weight loss, even when adjusted for age and BMI. CONCLUSIONS: We have demonstrated that after 6 months of bariatric surgery, there is significant increase in the UCP2 expression. Additionally, the expression of UCP2 and PLIN1 genes influences the resting metabolic rate in obese individuals and could predict the weight loss after bariatric surgery. PMID- 27376366 TI - How can we restore biodiversity and ecosystem services in mining and industrial sites? PMID- 27376367 TI - Occurrence of Legionella in wastewater treatment plants linked to wastewater characteristics. AB - In recent years, the occurrence of Legionella in wastewater treatment plants (WWTP) has often been reported. However, until now there is limited knowledge about the factors that promote Legionella's growth in such systems. The aim of this study was to investigate the chemical wastewater parameters that might be correlated to the concentration of Legionella spp. in WWTP receiving industrial effluents. For this purpose, samples were collected at different processes in three WWTP. In 100 % of the samples taken from the activated sludge tanks Legionella spp. were detected at varying concentrations (4.8 to 5.6 log GU/mL) by the quantitative real-time polymerase chain reaction method, but not by the culture method. Statistical analysis with various parameters yielded positive correlations of Legionella spp. concentration with particulate chemical oxygen demand, Kjeldahl nitrogen and protein concentration. Amino acids were quantified in wastewater and activated sludge samples at concentrations that may not support the growth of Legionella, suggesting that in activated sludge tanks this bacterium multiplied in protozoan hosts. PMID- 27376369 TI - Depletion of tropospheric ozone associated with mineral dust outbreaks. AB - From May to September 2012, ozone reductions associated with 15 Saharan dust outbreaks which occurred between May to September 2012 have been evaluated. The campaign was performed at a mountain station located near the eastern coast of the Iberian Peninsula. The study has two main goals: firstly, to analyze the decreasing gradient of ozone concentration during the course of the Saharan episodes. These gradients vary from 0.2 to 0.6 ppb h(-1) with an average value of 0.39 ppb h(-1). The negative correlation between ozone and coarse particles occurs almost simultaneously. Moreover, although the concentration of coarse particles remained high throughout the episode, the time series shows the saturation of the ozone loss. The highest ozone depletion has been obtained during the last hours of the day, from 18:00 to 23:00 UTC. Outbreaks registered during this campaign have been more intense in this time slot. The second objective is to establish from which coarse particle concentration a significant ozone depletion can be observed and to quantify this reduction. In this regard, it has been confirmed that when the hourly particle concentration recorded during the Saharan dust outbreaks is above the hourly particle median values (N > N median), the ozone concentration reduction obtained is statistically significant. An average ozone reduction of 5.5 % during Saharan events has been recorded. In certain cases, this percentage can reach values of higher than 15 %. PMID- 27376368 TI - Antimicrobial activity against Gram-positive and Gram-negative bacteria during gatifloxacin degradation by hydroxyl radicals. AB - Gatifloxacin, an antimicrobial drug belonging to the fluoroquinolone family, is active against Gram-positive and Gram-negative bacteria and is extensively used for the control of infections in humans. The presence of the drug in environmental matrices has already been reported. This study investigated the degradation of gatifloxacin in water by hydroxyl radicals generated by the UV254 nm/H2O2 process ([Formula: see text] 0.4-2.4 mmol L-1) and evaluated the capacity of the radicals to reduce the antimicrobial activity against Gram-positive and Gram-negative bacteria. Acute toxicity assays were performed with Vibrio fischeri, and the degradation products were proposed. The hydroxyl radicals formed in the processes were able to degrade the fluoroquinolone and remove the antimicrobial activity from the aqueous solution. Approximately 97 % gatifloxacin degradation was observed after applying 2.4 mmol L-1 of initial H2O2 concentration and 20 min of UVC254nm irradiation (130 J s-1). The acute toxicity assays showed that the toxicity of the treated solution for V. fischeri increased as the gatifloxacin concentration in the solution decreased. PMID- 27376370 TI - Prevalence of hypertension and its associated factors in contaminated areas of the Santos-Sao Vicente Estuarine region and Bertioga, Brazil: 2006-2009. AB - In Brazil, cardiovascular diseases account for 33% of deaths and the prevalence of hypertension is of approximately 22%. The Santos and Sao Vicente Estuarine System is the most important example of environmental degradation by chemicals from industrial sources. The aim of the present study was to evaluate the prevalence of hypertension and its associated factors in the population of this estuary in the period 2006-2009. A cross-sectional study was conducted to assess the aforementioned prevalence of hypertension in the evaluated areas, as well as risk factors for this disease in four contaminated areas located in the Estuary, and one area outside Estuary, the city of Bertioga. Associations between categorical variables were tested using Pearson's chi-square test incorporating Yates' correction, or Fisher's exact test. Single and multiple logistic regression models were applied to evaluate the risk factors for hypertension. The highest prevalence of hypertension was found in Continental Sao Vicente (28.4%). The risk factors for hypertension were the following: living in Center of Cubatao (OR: 1.3; IC95%: 1.0 - 1.6) and Continental Sao Vicente (OR: 1.4; IC95%: 1.1 - 1.8); illiterate (OR: 1.9; IC95%: 1.1 - 3.2); living in the area for more than 20 years (OR: 1.2; IC95%: 1.0 - 1.5); group of people aged 36-60 years (OR: 3.9; IC95%: 3.3 - 4.6) and who have had past occupational exposure (OR: 1.3; IC95%: 1.1 - 1.6). Results indicate that living in contaminated areas, especially for a longer time, is a risk factor for hypertension. PMID- 27376371 TI - Hispanics' Satisfaction with Free Clinic Providers: An Analysis of Patient Centered Medical Home Characteristics. AB - Hispanic Americans are less likely to be insured and they experience cultural and linguistic barriers that may prevent them from obtaining necessary and preventive healthcare. Adoption of Patient Centered Medical Home (PCMH) concepts in healthcare settings utilized by Hispanics could improve Hispanic patients' satisfaction with their healthcare providers. This study examined the association between Spanish-speaking and non-Spanish-speaking patients' perceptions of PCMH characteristics and satisfaction with the provider. Data were collected using a self-administered survey from two unaffiliated free clinics. Logistic regression modeled the associations between patients' perceptions of PCMH and their satisfaction with their provider, and their desire to see the same provider in the future. The sample consisted of 367 adults; 44 % were Spanish-speaking. Spanish-speaking patients were younger, less educated, and had fewer chronic conditions than non-Spanish-speaking patients. In adjusted analyses for each population, better ratings of the provider's communication skills were associated with increased satisfaction with the provider (Spanish-speaking: OR = 8.33, 95 % CI = 2.19-31.76; non-Spanish-speaking: OR = 31.39, 95 % CI = 6.91-142.62), and willingness to see the provider again (Spanish-speaking: OR = 12.54, 95 % CI = 2.80-56.24; non-Spanish-speaking: OR = 8.77, 95 % CI = 2.40-31.96). Among Spanish speakers, lower perceived discrimination was associated with 137 % increased odds and higher perceived staff helpfulness had 212 % increased odds of seeing the provider again. Relative to other PCMH components, interpersonal skills were the most important factors in patient satisfaction with free clinics. Increased training for clinicians on cultural competence and clinician-patient communication may lead to improved patient satisfaction for both Spanish and non Spanish speakers seen at free clinics, particularly clinics in states without Medicaid expansion. PMID- 27376374 TI - Biographic Characteristics and Factors Perceived as Affecting Female and Male Careers in Academic Surgery: The Tenured Gender Battle to Make It to the Top. AB - PURPOSE: Given the high attrition rate in the field of academic surgery, we aimed to characterise the professional and personal situations of female and male academic surgeons as well as to gather data on their respective perceptions of career advancement and work satisfaction. METHODS: We conducted a cross-sectional survey in Germany, inviting all identifiable academically highly qualified female surgeons and their male counterparts in a 1:2 ratio to participate. An anonymous 103-item online questionnaire was designed and the data collected between July and September 2014. RESULTS: The questionnaire was sent to 93 female and 200 male surgeons, of whom 63 women (67.7%) and 70 men (35.0%) replied. The average age was 47.5 and 47.1 years, respectively. Respondents identified 'high degree of expertise', 'ambition', and 'clarity of one's professional aims' as important factors affecting professional career development. Both groups felt 'workload', 'working hours/shifts', and 'gender' to be a hindrance, the latter of significantly greater importance to female surgeons. The mean work satisfaction scores were high in both female (69.5%) and male (75.7%) surgeons. The predictors 'support from superiors' (standardised beta coefficient = 0.41) and 'manual aptitude' (beta = 0.41) contributed incrementally to the variance in 'high degree of work satisfaction' (90-100%) observed for female surgeons. However, childcare provided by 'kindergarten/creche/after-school care' had the greatest negative predictive value (beta = -1.33). CONCLUSIONS: Although there are many parallels, female faculty members experience the culture of academic surgery to some extent differently from their male counterparts, especially when impacted by parenthood and childcare. Faculty development programmes need to develop strategies to improve perceived equality in career opportunities by respecting individuals' requirements as well as offering gender-appropriate career guidance. PMID- 27376373 TI - Efficacy and Treatment Costs of Monotherapy with bDMARDs in the Treatment of Rheumatoid Arthritis in Patients Intolerant to or Inappropriate to Continue Treatment with Methotrexate. AB - INTRODUCTION: Only limited information is available on cost efficacy of the various biological agents used to treat patients with rheumatoid arthritis with intolerance or for whom it would be inappropriate to continue treatment with conventional agents. We estimated the efficacy and treatment costs of monotherapy with biological agents in the treatment of this group of patients. METHODS: Data from two previous meta-analyses in the treatment of patients who are intolerant to methotrexate (MTX), or for whom it would be inappropriate to continue treatment with MTX was used. Pharmacoeconomic comparison between biological agents was carried out to estimate the respective cost for the number needed to treat (NNT) compared to placebo using both American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria. The analysis involved the four agents approved in Italy: adalimumab (ADA), etanercept (ETN), certolizumab pegol (CTZ), and tocilizumab (TCZ). A six-month period was considered sufficient to understand the most important differences in efficacy and treatment costs. Direct medical costs, including pharmacological therapy, administration and monitoring were considered. RESULTS: Using both ACR and EULAR criteria, TCZ (intravenous [iv]/subcutaneous [sc]) had a lower NNT than the other agents. The difference in NNT observed for ETN was more pronounced with EULAR criteria, whereas in the comparison with ADA, the most sensitive differences were observed with ACR criteria. ETN had the lowest treatment cost (?6402.19), followed by ADA (?6698.84), TCZ sc (?6887.61), and TCZ iv (?7130.83). TCZ sc had the lowest cost for NNT with both ACR and EULAR criteria. The differences compared to ETN and ADA were significant and related with the level of efficacy. Sensitivity analysis confirmed these results. CONCLUSION: TCZ is a cost-effective therapeutic option compared to other tumor necrosis factor-alpha inhibitors (ADA, ETA, CTZ) as first-line monotherapy for patients who are intolerant to MTX, or for whom it is inappropriate to continue treatment with MTX. FUNDING: Roche SpA. PMID- 27376375 TI - Experimental infection with non-cytopathic bovine viral diarrhea virus 1 in mice induces inflammatory cell infiltration in the spleen. AB - Previously, our study showed that oral inoculation of mice with cytopathic (cp) bovine viral diarrhea virus (BVDV) led to lymphocyte depletion and increased numbers of megakaryocytes in the spleen as well as thrombocytopenia and lymphopenia. In the present study, to investigate the possible differences in the detection of viral antigen, histopathological lesions, and hematologic changes between non-cytopathic (ncp) BVDV1 and cp BVDV1, mice were orally administered low and high doses of ncp BVDV1 and were necropsied at days 0, 2, 5, and 9 postinfection (pi). None of the ncp BVDV1-infected mice exhibited clinical signs of illness, unlike those infected with cp BVDV1. Statistically significant thrombocytopenia was observed during ncp BVDV1 infection, and lymphopenia was found only in mice infected with a high dose at day 9 pi. Interestingly, ncp BVDV1 infection increased the numbers of basophils, eosinophils, neutrophils, and monocytes in some infected mice. Viral antigen was detected in the lymphocytes of the spleen, mesenteric lymph nodes, Peyer's patches, and bone marrow by immunohistochemistry. Lymphoid depletion was evident in the mesenteric lymph nodes of mice infected with a high dose and also found in the Peyer's patches of some infected mice. Infiltration of inflammatory cells, including neutrophils and monocytes, and an increased number of megakaryocytes were seen in the spleen. These results suggest that the distribution of viral antigens is not associated with the presence of histopathological lesions. Inflammatory cell infiltration was observed in the spleens as a result of viral replication and may be attributable to the host reaction to ncp BVDV1 infection. Together, these findings support the possibility that mice can be used as an animal model for BVDV infection. PMID- 27376372 TI - Localization of the delta opioid receptor and corticotropin-releasing factor in the amygdalar complex: role in anxiety. AB - It is well established that central nervous system norepinephrine (NE) and corticotropin-releasing factor (CRF) systems are important mediators of behavioral responses to stressors. More recent studies have defined a role for delta opioid receptors (DOPR) in maintaining emotional valence including anxiety. The amygdala plays an important role in processing emotional stimuli, and has been implicated in the development of anxiety disorders. Activation of DOPR or inhibition of CRF in the amygdala reduces baseline and stress-induced anxiety like responses. It is not known whether CRF- and DOPR-containing amygdalar neurons interact or whether they are regulated by NE afferents. Therefore, this study sought to better define interactions between the CRF, DOPR and NE systems in the basolateral (BLA) and central nucleus of the amygdala (CeA) of the male rat using anatomical and functional approaches. Irrespective of the amygdalar subregion, dual immunofluorescence microscopy showed that DOPR was present in CRF containing neurons. Immunoelectron microscopy confirmed that DOPR was localized to both dendritic processes and axon terminals in the BLA and CeA. Semi quantitative dual immunoelectron microscopy analysis of gold-silver labeling for DOPR and immunoperoxidase labeling for CRF revealed that 55 % of the CRF neurons analyzed contained DOPR in the BLA while 67 % of the CRF neurons analyzed contained DOPR in the CeA. Furthermore, approximately 41 % of DOPR-labeled axon terminals targeted BLA neurons that expressed CRF while 29 % of DOPR-labeled axon terminals targeted CeA neurons that expressed CRF. Triple label immunofluorescence microscopy revealed that DOPR and CRF were co-localized in common cellular profiles that were in close proximity to NE-containing fibers in both subregions. These anatomical results indicate significant interactions between DOPR and CRF in this critical limbic region and reveal that NE is poised to regulate these peptidergic systems in the amygdala. Functional studies were performed to determine if activation of DOPR could inhibit the anxiety produced by elevation of NE in the amygdala using the pharmacological stressor yohimbine. Administration of the DOPR agonist, SNC80, significantly attenuated elevated anxiogenic behaviors produced by yohimbine as measured in the rat on the elevated zero maze. Taken together, results from this study demonstrate the convergence of three important systems, NE, CRF, and DOPR, in the amygdala and provide insight into their functional role in modulating stress and anxiety responses. PMID- 27376378 TI - [Not Available]. PMID- 27376377 TI - The complete genome sequence of a novel Fusarium graminearum RNA virus in a new proposed family within the order Tymovirales. AB - The complete nucleotide sequence of Fusarium graminearum deltaflexivirus 1 (FgDFV1), a novel positive single-stranded (+ss) RNA mycovirus, was sequenced and analyzed. The complete genome of FgDFV1/BJ59 was shown to be 8246 nucleotides (nt) long excluding the poly(A) tail. FgDFV1/BJ59 was predicted to contain a large open reading frame (ORF 1) and four smaller ORFs (2-5). ORF1 encodes a putative replication-associated polyprotein (RP) of 2042 amino acids (aa) and contains three conserved domains, viral RNA methyltransferase (Mtr), viral RNA helicase (Hel) and RNA-dependent RNA polymerase (RdRp). ORFs 2-5 encode four putative small hypothetical proteins (12-18 kDa) with unknown biological functions. Phylogenetic analysis based on RP sequences indicated that FgDFV1 is phylogenetically related to soybean leaf-associated mycoflexivirus 1 (SlaMyfV1) and Sclerotinia sclerotiorum deltaflexivirus 1 (SsDFV1), which form a well supported and independent group belonging to a newly proposed family Deltaflexiviridae within the order Tymovirales. However, FgDFV1 is markedly different from SsDFV1 and SlaMyfV1 in genome organization and nucleotide sequence. FgDFV1 may represent an additional species in the new genus Deltaflexivirus or possibly a new genus in the proposed family Deltaflexiviridae. PMID- 27376376 TI - The Vibrio parahaemolyticus-infecting bacteriophage qdvp001: genome sequence and endolysin with a modular structure. AB - Vibrio parahaemolyticus, a marine pathogen, is a causative agent of gastroenteritis in humans after consumption of contaminated seafood. In recent years, infections with V. parahaemolyticus have become an increasingly frequent factor in microbial food poisoning; therefore, it is urgent to figure out ways to control Vibrio parahaemolyticus. Endolysins, lytic enzymes encoded by bacteriophages, have been regarded as a therapeutic alternative to antibiotics in control of bacterial growth and have been successfully utilized in various areas. Here, we report the full genome sequence of the novel phage qdvp001, which lyses Vibrio parahaemolyticus 17802. The qdvp001 genome consists of a 134,742-bp DNA with a G+C content of 35.35 % and 227 putative open reading frames. Analysis revealed that the qdvp001 open reading frames encoded various putative functional proteins with a putative endolysin gene (ORF 60). No holin genes were identified in qdvp001. ORF 60 was cloned and expressed. The results showed that the purified endolysin Lysqdvp001 had a high hydrolytic activity toward Vibrio parahaemolyticus and a broader spectrum compared to that of the parental bacteriophage qdvp001. Thus, purified endolysin Lysqdvp001 has a potential to be used as an antibacterial agent in the future. PMID- 27376379 TI - [Not Available]. PMID- 27376380 TI - [Not Available]. PMID- 27376381 TI - [Not Available]. PMID- 27376382 TI - [Not Available]. PMID- 27376383 TI - [Not Available]. PMID- 27376384 TI - [Not Available]. PMID- 27376385 TI - [Not Available]. PMID- 27376386 TI - [Not Available]. PMID- 27376387 TI - [Not Available]. PMID- 27376388 TI - [Not Available]. PMID- 27376389 TI - [Not Available]. PMID- 27376390 TI - [Not Available]. PMID- 27376391 TI - [Not Available]. PMID- 27376393 TI - [Not Available]. PMID- 27376392 TI - [Not Available]. PMID- 27376394 TI - [Not Available]. PMID- 27376395 TI - A Plasmonic Platform with Disordered Array of Metal Nanoparticles for Three-Order Enhanced Upconversion Luminescence and Highly Sensitive Near-Infrared Photodetector. AB - Three-order enhanced upconversion luminescence from upconversion nanoparticles is suggested by way of a promising platform utilizing a disordered array of plasmonic metal nanoparticles. Its application toward highly sensitive NIR photodetectors is discussed. PMID- 27376396 TI - Insights into the structural patterns of the antileishmanial activity of bi- and tricyclic N-heterocycles. AB - The influence of various structural patterns in a series of novel bi- and tricyclic N-heterocycles on the activity against Leishmania major and Leishmania panamensis has been studied and compounds that are active in the low micromolar region have been identified. Both quinolines and tetrahydrooxazinoindoles (TOI) proved to have significant antileishmanial activities, while substituted indoles were inactive. We have also showed that a chloroquine analogue induces Leishmania killing by modulating macrophage activation. PMID- 27376397 TI - Indicators of a health-promoting local food environment: a conceptual framework to inform urban planning policy and practice. PMID- 27376398 TI - The importance of personality and life-events in anxious depression: from trait to state anxiety. AB - OBJECTIVES: Anxious depression is associated with severe impairment and bad prognoses. We hypothesize that recent life-events are associated with more anxiety in late-life depression and that this is conditional upon the level of certain personality traits. METHOD: Baseline data of the Netherlands Study of Depression in Older Persons (NESDO) were used. In 333 patients (>=60 years) suffering from a major depressive disorder, anxiety was assessed with the BAI, personality traits with the NEO-FFI and the Mastery Scale, and life-events with the Brugha questionnaire. Multiple linear regression analyses were applied with anxiety severity as dependent and life-events and personality traits as independent variables. RESULTS: 147 patients (44.1%) had recently experienced one or more life-events. The presence of a life-event is not associated with anxiety (p = .161) or depression severity (p = .440). However, certain personality traits interacted with life-events in explaining anxiety severity. Stratified analyses showed that life-events were associated with higher anxiety levels in case of high levels of neuroticism and openness and low levels of conscientiousness or mastery. CONCLUSIONS: In the face of a life-event, personality traits may play a central role in increased anxiety levels in late-life depression. PMID- 27376399 TI - Cotesia vestalis parasitization suppresses expression of a Plutella xylostella thioredoxin. AB - Thioredoxins (Trxs) are a family of small, highly conserved and ubiquitous proteins involved in protecting organisms against toxic reactive oxygen species. In this study, a typical thioredoxin gene, PxTrx, was isolated from Plutella xylostella. The full-length cDNA sequence is composed of 959 bp containing a 321 bp open reading frame that encodes a predicted protein of 106 amino acids, a predicted molecular weight of 11.7 kDa and an isoelectric point of 5.03. PxTrx was mainly expressed in larval Malpighian tubules and the fat body. An enriched recombinant PxTrx had insulin disulphide reductase activity and stimulated Human Embryonic Kidney 293 (HEK293) cell proliferation. It also protected supercoiled DNA and living HEK293 cells from H2 O2 -induced damage. Parasitization by Cotesia vestalis and injections of 0.05 and 0.01 equivalents of C. vestalis Bracovirus (CvBv), the symbiotic virus carried by the parasitoid, led to down-regulation of PxTrx expression in host fat body. Taken together, our results indicate that PxTrx contributes to the maintenance of P. xylostella cellular haemostasis. Host fat body expression of PxTrx is strongly attenuated by parasitization and by injections of CvBv. PMID- 27376400 TI - Apatinib for the treatment of gastric cancer. AB - INTRODUCTION: Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor 2, has demonstrated encouraging anti-cancer activity in gastric cancer within both in vitro and in vivo models. AREAS COVERED: Apatinib's efficacy, tolerability and safety have been evaluated in one Phase II and one Phase III study in metastatic/advanced gastric cancer. In this review, we focus on the mechanism of action of apatinib, its pharmacokinetic profile and its clinical activity in the treatment of advanced/metastatic gastric cancer. Expert commentary: Unfortunately, as yet, there is no definitive biomarker data for apatinib in gastric cancer. PMID- 27376401 TI - Bacterial infections in HIV-infected children admitted with severe acute malnutrition in Durban, South Africa. AB - BACKGROUND: Bacterial infections in HIV-infected children admitted with severe acute malnutrition (SAM) contribute to higher mortality and poorer outcomes. This study describes the spectrum of bacterial infections in antiretroviral treatment (ART)-naive, HIV-infected children admitted with SAM. METHODS: Between July 2012 and February 2015, 82 children were prospectively enrolled in the King Edward VIII Hospital, Durban. Specimens obtained on and during admission for microbiological evaluation, if clinically indicated, included blood, urine (obtained by catheterisation or suprapubic aspiration), induced sputum and cerebrospinal fluid. All positive bacterial cultures between admission and 30 days after enrollment were documented and characterised into samples taken either within 2 days of admission (infections on admission) or within 2-30 days of admission (hospital-acquired infections, HAIs). RESULTS: On admission, 67% of patients had abnormal white blood cell counts (WBCC) (>12 or <4 * 109/L) and 70% had elevated CRP; 65% were classified as severely immunosuppressed according to the WHO immunological classification.1 A pathogen was isolated on the admission blood culture in four patients (6%) and in 27% of urine specimens. HAIs were predominately Gram-negative (39/43), and 39.5% were extended-spectrum beta lactamase-positive. Mortality was not significantly associated with isolation of a bacterial pathogen. CONCLUSIONS: Routine pre-hospital administration of antibiotics as per the Integrated Management of Childhood Illness (IMCI) guidelines may be responsible for the low rates of positive admission blood cultures. HAIs with drug-resistant Gram-negative organisms are an area of concern and strategies to improve the prevention of HAIs in this vulnerable population are urgently needed. PMID- 27376402 TI - Fast blood-flow simulation for large arterial trees containing thousands of vessels. AB - Blood flow modelling has previously been successfully carried out in arterial trees to study pulse wave propagation using nonlinear or linear flow solvers. However, the number of vessels used in the simulations seldom grows over a few hundred. The aim of this work is to present a computationally efficient solver coupled with highly detailed arterial trees containing thousands of vessels. The core of the solver is based on a modified transmission line method, which exploits the analogy between electrical current in finite-length conductors and blood flow in vessels. The viscoelastic behaviour of the arterial-wall is taken into account using a complex elastic modulus. The flow is solved vessel by vessel in the frequency domain and the calculated output pressure is then used as an input boundary condition for daughter vessels. The computational results yield pulsatile blood pressure and flow rate for every segment in the tree. This solver is coupled with large arterial trees generated from a three-dimensional constrained constructive optimisation algorithm. The tree contains thousands of blood vessels with radii spanning ~1 mm in the root artery to ~30 MUm in leaf vessels. The computation takes seconds to complete for a vasculature of 2048 vessels and less than 2 min for a vasculature of 4096 vessels on a desktop computer. PMID- 27376403 TI - Complete response in metastatic renal cell carcinoma after radiotherapy and everolimus: a clinical case and review of the literature. AB - We report the case of a man affected by renal cell carcinoma with vertebral metastases, who presented a radiological complete response after systemic treatment with everolimus. PMID- 27376404 TI - Economic impact of expanded use of biologic therapy for the treatment of rheumatoid arthritis and Crohn's disease in Argentina, Brazil, Colombia, and Mexico. AB - OBJECTIVES: To estimate economic impact resulting from increased biologics use for treatment of rheumatoid arthritis (RA) and Crohn's disease (CD) in Argentina, Brazil, Colombia, and Mexico. METHODS: The influence of increasing biologics use for treatment of RA during 2012-2022 and for treatment of CD during 2013-2023 was modeled from a societal perspective. The economic model incorporated current and projected medical, indirect, and drug costs and epidemiologic and economic factors. Costs associated with expanded biologics use for RA were compared with non-expanded use in Argentina, Brazil, Colombia, and Mexico. A similar analysis was conducted for CD in Brazil, Colombia, and Mexico. RESULTS: Accounting for additional costs of biologics and medical and indirect cost offsets, the model predicts that expanded use of biologics for patients with RA from 2012 to 2022 will result in cumulative net cost savings of ARS$2.351 billion in Argentina, R$9.004 billion in Brazil, COP$728.577 billion in Colombia, and MXN$18.02 billion in Mexico; expanded use of biologics for patients with CD from 2013 to 2023 will result in cumulative net cost savings for patients with CD of R$0.082 billion in Brazil, COP$502.74 billion in Colombia, and MXN$1.80 billion in Mexico. Indirect cost offsets associated with expanded biologics use were a key driver in reducing annual per-patient net costs for RA and CD. LIMITATIONS: Future economic projections are limited by the potential variance between projected and actual future values of biologic prices, wages, medical costs, and gross national product for each country. CONCLUSIONS: Increasing biologics use to treat RA and CD may limit cost growth over time by reducing medical and indirect costs. These findings may inform policy decisions regarding biologics use in Argentina, Brazil, Colombia, and Mexico. PMID- 27376406 TI - Pressure-induced exotic states in rare earth hexaborides. AB - Finding the exotic phenomena in strongly correlated electron systems (SCESs) and understanding the corresponding microphysics have long been the research frontiers of condensed matter physics. The remarkable examples for the intriguing phenomena discovered in past years include unconventional superconductivity, heavy Fermion behaviors, giant magneto-resistance and so on. A fascinating type of rare earth hexaboride RB6 (R = Sm, Yb, Eu and Ce) belongs to a strongly correlated electron system (SCES), but shows unusual ambient-pressure and high pressure behaviors beyond the phenomena mentioned above. Particularly, the recent discovery of the coexistence of an unusual metallic surface state and an insulating bulk state in SmB6, known to be a Kondo insulator decades ago, by theoretical calculations and many experimental measurements creates new interest for the investigation of the RB6. This significant progress encourages people to revisit the RB6 with an attempt to establish a new physics that links the SCES and the unusual metallic surface state which is a common feature of a topological insulator (TI). It is well known that pressure has the capability of tuning the electronic structure and modifying the ground state of solids, or even inducing a quantum phase transition which is one of the kernel issues in studies of SCESs. In this brief review, we will describe the progress in high pressure studies on the RB6 based on our knowledge and research interests, mainly focusing on the pressure-induced phenomena in YbB6 and SmB6, especially on the quantum phase transitions and their connections with the valence state of the rare earth ions. Moreover, some related high-pressure results obtained from CeB6 and EuB6 are also included. Finally, a summary is given in the conclusions and perspectives section. PMID- 27376405 TI - Effects of Rosuvastatin and MiR-126 on Myocardial Injury Induced by Acute Myocardial Infarction in Rats: Role of Vascular Endothelial Growth Factor A (VEGF A). AB - BACKGROUND The present study investigated the effects of VEGF-A targeted by miR 126 on myocardial injury after acute myocardial infarction (AMI) in rats, along with the contributions of rosuvastatin to the synergic effect. MATERIAL AND METHODS SD rats were obtained to construct AMI models by ligating their left anterior descending coronary arteries (LAD). We conducted echocardiography to check the 6 involved indexes: left ventricular ejection fractions (LVEF), fractional shortening (FS), left ventricular end-systolic volume (LVV), left ventricular end-diastolic volume (LVVd), cardiac output (CO), and heart rate (HR). Moreover, antibody sandwich enzyme-linked immunosorbent assay was carried out to determine MI markers: creatine kinase (CK), CK Isoenzyme (CK-MB), and Troponin I (cTn I). Dual-Luciferase Reporter Assay was performed to confirm the targeting of miR-126 and VEGF-A. MTT assay provided insight into the proliferation of myocardial fibroblasts. Finally, RT-RCR and Western blot were used for the detection of miR-126 and VEGF-A expressions in vivo and in vitro. RESULTS Luciferase activity assay showed that miR-126 transfection significantly decreased the relative luciferase activity in HEK293T cells when it was bound to normal 3' UTR of VEGF-A (P<0.05). In comparison to the control group, rats in the AMI model group had significantly lower LVEF, FS, and CO, and substantially higher LVVs, LVVd, HR, CK/U, CK-MB/U, and cTn-1/U (all P<0.05). Down-regulated miR-126 and up-regulated VEGF-A were also observed in MI models (P<0.05). CONCLUSIONS miR-126 and rosuvastatin have protective effects on AMI risk, and VEGF-A antagonizes effects on AMI is imposed by. PMID- 27376407 TI - Excited Oxidized-Carbon Nanodots Induced by Ozone from Low-Temperature Plasma to Initiate Strong Chemiluminescence for Fast Discrimination of Metal Ions. AB - Carbon nanodots (C-dots) are recently well examined due to the emissions with color-tuning and nonblinking properties, while more studies are still needed for the appropriate understanding and application of distinct emissions. In this work, we found the emission of chemiluminescence (CL) by introducing low temperature plasma (LTP) into C-dots solutions without any reagent added, whose intensity was affected by the presence of different metal ions. Based on both experimental data and theoretical calculations, we found with the ozonation by ozone from LTP, excited oxidized-C-dots would be generated with the addition of ozone onto the conjugated double bonds of C-dots, and these excited species could directly initiate strong CL combining with the deactivation of excited species to the ground state. Significantly, the cross-reactive CL signals were obtained from different kinds of C-dots with the presence of different metal ions. Therefore, a new sensor array (electronic tongue) composed of five different C-dots was designed for fast discrimination of metal ions, which achieved the accurate discrimination of 13 kinds of metal ions in pure water and real samples. It exhibited good reproducibility and sensitivity, which can be used for the quantitative analysis of metal ions such as showing a linear range from 4 * 10( 7) to 6 * 10(-5) mol.L(-1) (R(2) > 0.99) for Fe(3+) with a detection limit of 2.5 * 10(-7) mol.L(-1). This work not only provides a novel finding of CL from C-dots revealing explicit relationship between structures and CL properties, but also realizes the fast discrimination of metal ions, showing potentials in environmental monitoring and quality identifications. PMID- 27376408 TI - Automated SDS Depletion for Mass Spectrometry of Intact Membrane Proteins though Transmembrane Electrophoresis. AB - Membrane proteins are underrepresented in proteome analysis platforms because of their hydrophobic character, contributing to decreased solubility. Sodium dodecyl sulfate is a favored denaturant in proteomic workflows, facilitating cell lysis and protein dissolution; however, SDS impedes MS detection and therefore must be removed prior to analysis. Although strategies exist for SDS removal, they provide low recovery, purity, or reproducibility. Here we present a simple automated device, termed transmembrane electrophoresis (TME), incorporating the principles of membrane filtration, but with an applied electric current to ensure near-complete (99.9%) removal of the surfactant, including protein-bound SDS. Intact proteins are recovered in solution phase in high yield (90-100%) within 1 h of operation. The strategy is applied to protein standards and proteome mixtures, including an enriched membrane fraction from E. coli, resulting in quality MS spectra free of SDS adducts. The TME platform is applicable to both bottom-up MS/MS as well as LC-ESI-MS analysis of intact proteins. SDS-depleted fractions reveal a similar number of protein identifications (285) compared wit a non-SDS control (280), being highly correlated in terms of protein spectral counts. This fully automated approach to SDS removal presents a viable tool for proteome sample processing ahead of MS analysis. Data are available via ProteomeXchange, identifier PXD003941. PMID- 27376409 TI - Musculoskeletal disorders as a fatigue failure process: evidence, implications and research needs. AB - Mounting evidence suggests that musculoskeletal disorders (MSDs) may be the result of a fatigue failure process in musculoskeletal tissues. Evaluations of MSD risk in epidemiological studies and current MSD risk assessment tools, however, have not yet incorporated important principles of fatigue failure analysis in their appraisals of MSD risk. This article examines the evidence suggesting that fatigue failure may play an important role in the aetiology of MSDs, assesses important implications with respect to MSD risk assessment and discusses research needs that may be required to advance the scientific community's ability to more effectively prevent the development of MSDs. Practitioner Summary: Evidence suggests that musculoskeletal disorders (MSDs) may result from a fatigue failure process. This article proposes a unifying framework that aims to explain why exposure to physical risk factors contributes to the development of work-related MSDs. Implications of that framework are discussed. PMID- 27376412 TI - Correction: Dynamic ruffling distortion of the heme substrate in non-canonical heme oxygenase enzymes. AB - Correction for 'Dynamic ruffling distortion of the heme substrate in non canonical heme oxygenase enzymes' by Amanda B. Graves et al., Dalton Trans., 2016, 45, 10058-10067. PMID- 27376410 TI - A prospective comparative study to evaluate the displacement of four commercially available breast biopsy markers. AB - OBJECTIVE: Radiopaque markers are commonly deployed following breast biopsies to indicate the location of the targeted lesion. A frequently encountered complication is the displacement of these markers. This study compared the degree of displacement among four newer generation markers after stereotactic core needle biopsy. METHODS: 80 consecutive biopsies were performed at three breast centre sites. The markers included: HydroMARK((r)) (Mammotome, Cincinnati, OH), MammoMARKTM (Mammotome, Cincinnati, OH), MammoStarTM (Mammotome, Cincinnati, OH) and SecurMark((r)) (Hologic, Bedford, MA). Each marker was composed of a radiopaque core with a unique polymeric encasing component. Post-procedure mammograms were obtained and the degree of marker displacement was measured. RESULTS: MammoMARKTM exhibited the greatest mean net displacement, followed by HydroMARK((r)), SecurMark((r)) and MammoStarTM (13.9, 7.7, 5.8 and 4.7 mm, respectively), although these differences did not reach statistical significance (p = 0.398). 73% of the markers did not displace at all. However, in the 19 of 22 markers in which displacement occurred, the distance from the biopsy cavity was >10 mm. No statistically significant contributing factors to predict displacement were found. CONCLUSION: Newer generation biopsy markers perform comparably with one another. However, clinically significant and unpredictable marker displacement persists. Compared with multiple similar studies of older generation bare metallic markers, the overall displacement rate of newer generation markers seems to be lower, possibly owing to the use of polymeric embedding agents that self-expand within the biopsy cavity. ADVANCES IN KNOWLEDGE: This article compares the post-procedure displacement of breast biopsy markers, which have not been evaluated or discussed in detail since markers with polymeric embedding agents gained widespread use. PMID- 27376411 TI - Separate and combined effects of genetic variants and pre-treatment whole blood gene expression on response to exposure-based cognitive behavioural therapy for anxiety disorders. AB - OBJECTIVES: Exposure-based cognitive behavioural therapy (eCBT) is an effective treatment for anxiety disorders. Response varies between individuals. Gene expression integrates genetic and environmental influences. We analysed the effect of gene expression and genetic markers separately and together on treatment response. METHODS: Adult participants (n <= 181) diagnosed with panic disorder or a specific phobia underwent eCBT as part of standard care. Percentage decrease in the Clinical Global Impression severity rating was assessed across treatment, and between baseline and a 6-month follow-up. Associations with treatment response were assessed using expression data from 3,233 probes, and expression profiles clustered in a data- and literature-driven manner. A total of 3,343,497 genetic variants were used to predict treatment response alone and combined in polygenic risk scores. Genotype and expression data were combined in expression quantitative trait loci (eQTL) analyses. RESULTS: Expression levels were not associated with either treatment phenotype in any analysis. A total of 1,492 eQTLs were identified with q < 0.05, but interactions between genetic variants and treatment response did not affect expression levels significantly. Genetic variants did not significantly predict treatment response alone or in polygenic risk scores. CONCLUSIONS: We assessed gene expression alone and alongside genetic variants. No associations with treatment outcome were identified. Future studies require larger sample sizes to discover associations. PMID- 27376413 TI - Use of conducting polymers to facilitate neurite branching in schizophrenia related neuronal development. AB - Schizophrenia (SCZ) is a debilitating mental disorder which results in high healthcare and loss of productivity costs to society. This disease remains poorly understood, however there is increasing evidence suggesting a role for oxidative damage in the disease etiology. We aimed to examine the effect of the conducting polymer polypyrrole on the growth and morphology of both wildtype and neuregulin 1 knock out (NRG-1 +/-) explant cells. Polypyrrole is an organic conducting polymer known to be cytocompatible and capable of acting as a platform for effective stimulation of neurons. Here we demonstrate for the first time the ability of this material to mediate processes occurring in disease affected neurons: schizophrenic model cortical neurons. Prefrontal cortical cells were grown on conducting polymer scaffolds of specific composition and showed significantly increased neurite branching and outgrowth length on the polymers compared to controls. Concurrently, a more significant enhancement was seen in both parameters in the NRG-1 +/- model cells. This finding implies that conducting polymers such as polypyrrole may be utilised to overcome neuro functional deficits associated with neurological disease in humans. PMID- 27376414 TI - Highlights from the 51st EUCHEM conference on stereochemistry, Burgenstock, Switzerland, May 2016. PMID- 27376415 TI - Modern mass spectrometry for synthetic biology and structure-based discovery of natural products. AB - Covering: up to 2016In this highlight, we describe the current landscape for dereplication and discovery of natural products based on the measurement of the intact mass by LC-MS. Often it is assumed that because better mass accuracy (provided by higher resolution mass spectrometers) is necessary for absolute chemical formula determination (<=1 part-per-million), that it is also necessary for dereplication of natural products. However, the average ability to dereplicate tapers off at ~10 ppm, with modest improvement gained from better mass accuracy when querying focused databases of natural products. We also highlight some recent examples of how these platforms are applied to synthetic biology, and recent methods for dereplication and correlation of substructures using tandem MS data. We also offer this highlight to serve as a brief primer for those entering the field of mass spectrometry-based natural products discovery. PMID- 27376416 TI - Variations in leptin and insulin levels within one swimming season in non-obese female cold water swimmers. AB - AIM: We examined whether cold water swimming for seven consecutive months changes basal leptin and insulin concentrations and insulin sensitivity in healthy non obese women. MATERIALS AND METHODS: Fourteen recreational female swimmers aged 45 +/- 8.7 years, regularly swimming outdoors during winter months were exposed to cold water at least twice a week. Fasting blood samples were collected in October, January and April. Serum leptin, insulin and glucose concentrations were tested and insulin sensitivity was calculated using updated model HOMA2. RESULTS: Repeated cold water baths significantly increased insulin sensitivity and decreased insulin and leptin concentrations (p = 0.006, p = 0.032, p = 0.042, respectively). Leptin concentration positively correlated with body-mass index (BMI) and insulin level (r = 0.412, r = 0.868, respectively). Insulin level inversely correlated with insulin sensitivity and positively with glucose (r = 0.893, r = 0.166, respectively). No associations between leptin and insulin sensitivity were found. CONCLUSION: Regular cold water swimming may stimulate metabolic changes suggesting that leptin and insulin participate in adaptive metabolic mechanisms triggered by repeated cold exposure accompanied by mild exercise in healthy non-obese women. PMID- 27376417 TI - Mesoscale aggregation properties of C60 in toluene and chlorobenzene. AB - The mesoscale aggregation properties of C60 in two distinct aromatic solvents (toluene and chlorobenzene) and a practical range of concentrations (c = 1-2 and c = 1-5 mg mL(-1), respectively) were systematically explored by static/dynamic light scattering (SLS/DLS), small angle X-ray scattering (SAXS), depolarized dynamic light scattering (DDLS), and cryogenic transmission electron microscopy (cryo-TEM) analyses. The central observations were as follows: (1) aggregate species of sizes in the range of several hundred nanometers have been independently revealed by SLS, DLS, and DDLS analyses for both solvent systems. (2) DDLS and cryo-TEM measurements further revealed that while C60 clusters are notably anisotropic (rod-like) in chlorobenzene, they are basically isotropic (spherical) in toluene. (3) Detailed analyses of combined SLS and SAXS profiles suggested that varied, yet self-similar, solvent-induced aggregate units were responsible for the distinct (mesoscale) aggregation features noted above. (4) From a dynamic perspective, specially commissioned DLS measurements ubiquitously displayed two relaxation modes (fast and slow mode), with the second (slow) mode being q (wave vector) independent. While the fast mode in both solvent systems was basically diffusive by nature and leads to geometrical features in good agreement with the above static analyses, the slow mode was analyzed and tentatively suggested to reflect the effect of mutual confinement. (5) Micron scale aggregate morphology of drop-cast thin films displays similar contrasting features for the two solvent media used. Overall, this study suggests that solvent-induced, nanoscale, aggregate units may be a promising factor to control a hierarchy of microscopic aggregation properties of C60 solutions and thin films. PMID- 27376418 TI - Salivary testosterone responses to a physical and psychological stimulus and subsequent effects on physical performance in healthy adults. AB - OBJECTIVE: To address the rapid influence of testosterone (T) on neuromuscular performance, we compared the T and physical performance responses of adults exposed to a physical and psychological stimulus. DESIGN: A group of healthy men (n=12) and women (n=14) each completed three treatments using a randomised, crossover design: exercise involving five * ten-second cycle sprints, viewing a video clip with aggressive content and a control session. Salivary T concentrations, hand-grip strength (HGS) and countermovement jump peak power (CMJ PP) were assessed before and 15 minutes after each session. RESULTS: The relative changes in T (17+/-29%) and CMJ PP (-0.1+/-4.4%) following sprint exercise were superior to the aggressive video (-6.3+/-19%, -2.2+/-5.9%) and control (-4.8+/ 23%, -2.8+/-4.4%) treatments, respectively (p <=0.05). Pre-treatment T levels correlated (r= -0.58 to -0.61, p <0.05) with the T responses of men (sprint exercise) and women (sprint exercise, aggressive video), but no variables were significantly correlated with the relative changes in HGS or CMJ PP. CONCLUSIONS: Sprint exercise promoted a general rise in T and maintained CMJ PP, relative to the video and control treatments. In both sexes, those individuals with higher pre-test T levels tended to produce smaller T responses to one or more treatments. These data highlight the importance of stimulus selection and individual predispositions when attempting to acutely modify T and associated physical performance. PMID- 27376419 TI - Clinical impact of strict criteria for selectivity and lateralization in adrenal vein sampling. AB - INTRODUCTION: Selectivity index (SI) and lateralization index (LI) thresholds determine the adequacy of adrenal vein sampling (AVS) and the degree of lateralization. The purpose of this study was investigate the clinical outcome of patients whose adrenal vein sampling was interpreted using "strict criteria" (SC) (SIpre-stimuli>=3, SIpost-stimuli>=5 and LIpre-stimuli>=4, LIpost-stimuli>=4). MATERIALS AND METHODS: A retrospective review of 73 consecutive AVS procedures was performed and 67 were technically successful. Forty-three patients showed lateralization and underwent surgery, while 24 did not lateralize and were managed conservatively. Systolic blood pressure (SBP), diastolic blood pressure (DBP), kalemia (K(+)), and the change in number of blood pressure (BP) medications were recorded for each patient before and after AVS and potential surgery were performed. RESULTS: In the surgery group, BP and K(+) changed respectively from 160+/-5.3/100+/-2.0 mmHg to 127+/-3.3/80+/-1.9 (p <0.001) and from 3.00+/-0.10 to 4.4+/-0.09 (p <0.001). In the medically managed group, BP and K(+) changed respectively from 148+/-7.3/93+/-4.3 to 135+/-3.3/86+/-1.9 (p <0.001) and from 2.68+/-0.10 to 4.3+/-0.09. After surgery or AVS, the patients who took >=3 blood pressure medications were six (14.0%) in the lateralized group and 22 (91.7%) in the non-lateralized group (p <0.001). CONCLUSIONS: AVS interpretation with SC leads to significant clinical improvement in both patients who underwent surgery and those managed conservatively. PMID- 27376420 TI - Laparoscopic surgery for pancreatic insulinomas: an update. AB - Insulinomas are the most common functioning neuroendocrine tumors of the pancreas, occurring in almost 1-4 per 1 million persons each year. In contrast to other pancreatic neuroendocrine tumors, they are usually benign and solitary at the time of diagnosis. Due to their benign nature, surgical excision is the treatment of choice, with excellent long-term results. The introduction of minimally invasive techniques in the surgical treatment of insulinoma has been gaining popularity due to shorter length of hospital stay and better cosmetic results, with serious complications being comparable to those of open surgery. Preoperative localization is of paramount importance in the determination of the appropriate surgical approach. Many invasive and non-invasive methods exist for localization of an insulinoma. A combination of these modalities is usually adequate to preoperatively localize the vast majority of tumors. Laparoscopic ultrasound is mandatory to localize these tumors intraoperatively. Despite extensive experience in highly specialized centers producing encouraging results, no randomized trials have been realized to conclusively validate these case series, this partly due to the rarity of insulinoma in the population. In this article we present the current state of laparoscopic management of insulinoma delineating still unanswered issues and we underscore some of the technical details of the most common laparoscopic procedures employed. PMID- 27376421 TI - Cardiovascular safety of type 2 diabetes medications: Review of existing literature and clinical implications. AB - Type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD) and the cardiovascular effect of antidiabetic drugs are today critical medical issues, with the prevalence of T2DM in particular showing a steep increase worldwide, mainly due to unhealthy lifestyle habits. T2DM in association with obesity and other cardiovascular risk factors, results in the development of CVD, the leading cause of morbidity and mortality in patients with T2DM. Thus, treatment of T2DM is an individualized and complex challenge in which targeting cardiovascular risk factors is an important component in the decision making. Given the cardiovascular adverse events associated with rosiglitazone, both the Food and Drug Administration and the European Medicines Agency currently require the demonstration of cardiovascular safety of new antidiabetic drugs. Consequently, clinical trials to guarantee their cardiovascular safety are now obligatory. This review aims to summarize the available evidence on the cardiovascular effects and safety of the major drugs used in T2DM treatment and also to provide an overview of upcoming and ongoing clinical trials in this field. Our belief is that this review will be of substantial assistance to all medical doctors who are treating diabetic patients, namely primary care physicians, internal medicine doctors, endocrinologists, diabetologists and less well experienced personnel such as young doctors in training. PMID- 27376422 TI - Effects of ghrelin in energy balance and body weight homeostasis. AB - Ghrelin is a gut peptide composed of 28 amino acids mostly secreted in the gastric fundus mucosa. It was isolated and described in 1999 by Kojima et al. and only three years later its specific receptor, GHSR1a, was also identified. Ghrelin, the endogenous ligand for the GH secretagogue receptor, is the only peripheral orexigenic hormone that activates the receptors to be found especially in the appetite center (hypothalamus and pituitary gland). Ghrelin is present in human plasma in two forms: an inactive form known as deacylated ghrelin, and an active form called acylated ghrelin synthesized under the action of ghrelin O acyltransferase enzyme (GOAT). The literature even mentions an extremely complex ghrelin/GOAT/GHSR system involved in the regulation of human energy, metabolism and adaptation of energy homeostasis to environmental changes. In humans, there is a preprandial rise and a postprandial fall in plasma ghrelin levels, which strongly suggest that the peptide plays a physiological role in meal initiation and may be employed in determining the amount and quality of ingested food. Besides the stimulation of food intake, ghrelin determines a decrease in energy expenditure and promotes the storage of fatty acids in adipocytes. Thus, in the human body ghrelin induces a positive energy balance, an increased adiposity gain, as well as an increase in caloric storage, seen as an adaptive mechanism to caloric restriction conditions. In the current world context, when we are witnessing an increasing availability of food and a reduction of energy expenditure to a minimum level, these mechanisms have become pathogenic. As a consequence, the hypothesis that ghrelin is involved in the current obesity epidemic has been embraced by many scholars and researchers. PMID- 27376423 TI - Comparison of color-Doppler and qualitative and quantitative strain-elastography for differentiation of thyroid nodules in daily practice. AB - OBJECTIVE: Strain-elastography provides a new ultrasound-based method that can offer information about the stiffness of thyroid nodules as an indicator of malignancy. The aim of our study was to compare the utility of color-Doppler and strain-elastography in differentiating between benign and malignant nodules. DESIGN AND METHODS: 77 thyroid nodules (70 benign and 7 malignant) from 70 unselected patients (48 female/22 male, mean age 49.7+/-14.3 years) were evaluated with color-Doppler and elastography based on a five-scale elastogram score for qualitative elastography and strain ratio for quantitative elastography. As reference tissue we chose normal thyroid tissue [strain ratio a (SR a)] and cervical muscles [strain ratio b (SR b)]. The cytological or histological results were used as a reference standard. Diagnostic performances of qualitative and quantitative elastography were compared using ROC curves. RESULTS: Vascularization score 3 or 4 was associated with malignancy (p=0.024) as well as elastogram score 4 or 5 (p=0.070, n.s.s.). SR a was indicatively higher and SR b lower in the group of malignant nodules (p=0.065 and p=0.246, n.s.s.). The best cut-off points predicting malignancy were 3.32 for SR a (66.7% sensitivity, 83.3% specificity) and 0.10 for SR b (71.4% sensitivity, 67.1% specificity). CONCLUSION: In our study, the accuracy of elastography did not surpass other sonographic parameters in differentiating thyroid nodules. The technique can play a role as a supplementary parameter in assessment of malignancy to improve diagnostic efficacy. The best parameter is SR a, but SR b can serve as an alternative if SR a is not assessable. PMID- 27376424 TI - Vitamin D levels in a large Mediterranean cohort: reconsidering normal cut-off values. AB - OBJECTIVE: The determination of the normal range of 25-hydroxyvitamin D [25 (OH)D], though currently based on suppression of PTH levels, still remains a controversial issue. The 25-(OH)D levels exhibit gender and seasonal variability, the latter attributed in part to changes of insolation. DESIGN: The aim of this cross-sectional study was to estimate the levels of 25-(OH)D on the island of Crete and their correlation with metabolic, hormonal and bone turnover parameters. The study was performed over a period of five years and involved 8,183 male and female individuals (8,042 analyzed). RESULTS: Our results are as follows: (1) 25-(OH)D was significantly lower than expected (19.48+/-9.51 and 18.01+/-9.01 (ng/mL+SD) in males and females, respectively); (2) seasonal variation of 25-(OH)D was observed in both sexes (females < males), with values peaking in August; (3) a decline of 25-(OH)D was evident with advancing age, with lower levels in females compared to males up to menopause and no apparent difference between the genders thereafter; (4) levels of 25-(OH)D were lower in renal function impairment, diabetes/insulin resistance and inflammation, while no correlation was detectable in thyroid dysfunction; (5) normalization of PTH levels was observed at ~20 ng/mL 25-(OH)D. At the same cut-off level, a significant decrease of all measured bone turnover indices (b-ALP, osteocalcin and CTX) was evident. CONCLUSION: Based on the above data, it appears that a cut off level of 25-(OH)D close to 20 ng/mL better reflects the physiology of our population. PMID- 27376425 TI - Beneficial effect of dose escalation and surgical debulking in patients with acromegaly treated with somatostatin analogs in a Romanian tertiary care center. AB - BACKGROUND: Somatostatin analogs (SSA) are now considered standard therapy for acromegaly, as primary or adjunctive treatment after pituitary surgery. OBJECTIVE: To evaluate the efficacy of SSA and the effect of dose escalation in non-operated patients with acromegaly as compared to patients treated after pituitary surgery in a Romanian tertiary care center. DESIGN: Retrospective study of 73 consecutively evaluated patients with acromegaly treated with SSA, divided into 2 groups: 11 patients (4M/7F, 21-62 years) with primary treatment and 62 patients (22M/40F, 21-68 years) treated after surgery. They received Octreotide LAR 20-30 mg i.m./28 days or Lanreotide SR 30 mg i.m./14/10/7 days. Random serum growth hormone (GH) was measured using IRMA, sensitivity 0.2-0.01 MUg/L IGF-1 was measured using different assays and compared with ULN for age and sex. RESULTS: Overall, random GH <=2.5 MUg/L was attained in 39 patients (53.4%) and optimal GH <=1 ng/mL) in 30 patients (41%), while normal IGF-1 was recorded in 22/72 patients (30.5%). The final random GH <=2.5 MUg/L was achieved in 27.2% of non operated patients (3/11) as compared with 58% (36/62) of patients treated medically after pituitary surgery, p<0.05. Escalation of doses of SSA applied in 43 patients improved the number of controlled patients by 5 (12.1%, p=0.059) and the number of optimally controlled patients by 9.7%. Of the 8 patients who switched from Lanreotide to Octreotide, 2 patients achieved GH normalization. CONCLUSION: The rate of biochemical control via SSA treatment in patients with acromegaly could be improved by rise of the SSA dose or by debulking surgery. Occasionally, substituting one SSA for another may be of benefit. PMID- 27376426 TI - Genetic screening of non-classic CAH females with hyperandrogenemia identifies a novel CYP11B1 gene mutation. AB - OBJECTIVE: Congenital adrenal hyperplasia (CAH) is an endocrine autosomal recessive disorder with various symptoms of diverse severity. Mild hyperandrogenemia is the most commonclinical feature in non-classic CAH patients and 95% of the cases are identified by mutations in the CYP21A2 gene. In the present study, the second most common cause for non-classic CAH (NC-CAH), 11beta hydroxylase deficiency due to mutations in the CYP11B1 gene, is investigated. DESIGN: Screening of the CYP21A2 and CYP11B1 genes by direct sequencing was carried out for the detection of possible genetic defects in patients with suspected CAH. RES ULTS: It wasobserved that CYP11B1 variants co-exist only in rare cases along with mutations in CYP21A2 in patients clinically diagnosed with CAH. A total of 23 NC-CAH female patients out of 75 were identified with only one mutation in the CYP21A2 gene. The novel CYP11B1 gene mutation, p.Val484Asp, was identified in a patient with CAH in the heterozygous state. The structural characterization of the novel p.Val484Asp was found to likely cause distortion of the surrounding beta sheet and indirect destabilization of the cavity that occurs on the opposite face of the structural elements, leading to partial impairment of the enzymatic activity. CONCLUSIONS: CYP21A2 gene mutations are the most frequent genetic defects in cases of NC-CAH even when these patients are in the heterozygous state. These mutations have a diverse phenotype giving rise to a variable extent of cortisol synthesis impairment; it is also clear that CYP11B1 mutants are a rare type of defects causing CAH. PMID- 27376427 TI - The gonadotroph origin of null cell adenomas. AB - OBJECTIVE: The term "null cell" adenoma was first proposed in 1980 to designate pituitary adenomas lacking clinical, biochemical and morphological markers to disclose their cell origin. DESIGN: The aim of this study was to investigate the presence of alpha- and beta-gonadotropin subunits in clinically nonfunctioning pituitary tumors, which were initially immunonegative and thus diagnosed as null cell adenomas. For this reason, we reapplied immunohistochemistry using a more sensitive method comprising a tyramide signal amplification technique, combined with a polymer antibody immunohistochemical detection system. RESULTS: With this approach, all these previously negative tumors became positive for alpha- and beta-gonadotropin hormone subunits. CONCLUSIONS: Our results prove that so-called "null cell" adenomas produce alpha-SU or/and beta-FSH or beta-LH and therefore are gonadotrph adenomas in origin. PMID- 27376428 TI - Which is the best predictor of thyroid cancer: thyrotropin, thyroglobulin or their ratio? AB - OBJECTIVE: Since documented incidence of thyroid cancer has been rising over time, in part due to incidental small papillary cancer, several studies have been carried out to investigate the role of possible serum markers of thyroid cancer prior to surgery. DESIGN: Prospective cohort study. AIM: To investigate the role of thyroglobulin (Tg), thyrotropin (TSH) and the TSH:Tg, Tg:TSH ratio in the preoperative diagnosis of thyroid cancer. PATIENTS AND METHODS: Between January 2014 and January 2015, 202 of 242 consecutive patients scheduled for surgical treatment for thyroid disorders at Sisli Etfal Training and Research Hospital, General Surgery Clinic were included in the study. Prospective data collection included demographics, thyroid function tests, Tg levels, fine needle aspiration biopsy (FNAB) results (208 FNABs in 187 patients), surgical procedures and final histopathological examinations. RESULTS: There were 134 patients with benign thyroid diseases and 68 patients with thyroid gland malignancy. Preoperative Tg level was significantly lower in the malignant group (64 ng/mL vs. 20ng/mL, p<0.001, respectively), whereas there was no difference in TSH between groups. TSH:Tg levels were found to be significantly higher in patients with malignant thyroid diseases (0.24+/-1 vs. 0.87+/-3.4, p=0.024). Although univariate analysis showed that the TSH:Tg ratio was a predictor for thyroid malignancy (OR 0.001; 95% CI, 0.01-0.125; p=0.007) in conjunction with FNAB, multivariate analysis failed to demonstrate any statistical significance for any factor except FNAB. CONCLUSION: Preoperative assessment of serum Tg and TSH levels appear not to be helpful in identifying patients with thyroid cancer. However, a higher preoperative serum TSH:Tg ratio may hint at an increased risk for thyroid carcinoma. Further studies are needed to elucidate the potential role of preoperative laboratory values of thyroid function. PMID- 27376429 TI - Delayed diagnosis of disorder of sex development (DSD) due to P450 oxidoreductase (POR) deficiency. AB - CASE PRESENTATION: A 36-year old man, operated on for cryptorchidism at the age of 8 years, was referred to the Outpatient Clinic of Reproductive Endocrinology for investigation of infertility. Clinical examination revealed ambiguous genitalia: penis 4-5 cm, testicular volume 2-3 ml, hypospadias, hypertrophic foreskin and scrotum bifida. Mild hypertension was confirmed. No skeletal malformations were detected. DESIGN: Hormonal and electrolytic determinations as well as semen analysis were conducted. PCR of the coding regions of 17 hydroxylase/17,20 lyase (P450c17) and of P450 oxidoreductase (POR) genes was also performed. RESULTS: Normal levels of electrolytes, low levels of androgens, high levels of gonadotropins and 17-hydroxyprogesterone as well as azoospermia were detected. Karyotype was shown to be 46,XY. Both hCG and ACTH stimulation significantly increased 17-hydroxyprogesterone with no increase in androgens. The diagnosis was congenital adrenal hyperplasia with apparent combined P450c17 and P450c21 deficiency due to mutations in the POR gene. Sequencing of the POR gene revealed: one deletion in exon 12 (Del 1696_1698delGTC >del531Valine) and one missense mutation in exon 7 (A259G) as well as two polymorphisms: rs1057868 (C/T A503V) and rs1057870 (G/A S572S) in exons 12 and 13, respectively. No nucleotide changes were detected in the 8 exons of P450c17. CONCLUSIONS: Molecular findings were consistent with the diagnosis of P450 oxidoreductase deficiency. Despite this severe deficiency, skeletal malformations simulating Antley-Bixler syndrome, which usually characterize the most severe forms, were not confirmed. This discrepancy could be attributed to the differential impact of a POR variant on each one of the P450 enzymes. PMID- 27376430 TI - Adrenal malignant melanoma masquerading as a pheochromocytoma in a patient with a history of a multifocal papillary and medullary thyroid carcinoma. AB - OBJECTIVE: Adrenal masses usually represent benign and nonfunctional adrenal adenomas; however, primary or metastatic malignancy should also be considered. Discovery of an adrenal mass needs further evaluation in order to exclude malignancy and hormonal secretion. We present a rare case of a possibly primary adrenal malignant melanoma with imaging and biochemical features of a pheochromocytoma. CASE REPORT: A 61-year-old male farmer was referred for evaluation of a mass in the right supraclavicular region and a left adrenal lesion. The patient had a history of a multifocal papillary and medullary thyroid carcinoma. Laboratory tests revealed increased 24hour urinary dopamine and also increased serum calcitonin and neuron specific enolase. A pathology report of the resected right supraclavicular mass and left adrenal showed a malignant melanoma. CONCLUSION: This is a case of a possibly primary adrenal malignant melanoma with imaging and biochemical features of a pheochromocytoma. Although this case is very rare and there are rigid diagnostic criteria for the diagnosis of primary adrenal melanoma, it underlines the fact that the differential diagnosis of a dopamine secreting adrenal mass should include primary or metastatic malignant melanoma in order to determine the best diagnostic approach for the patient and select the most appropriate surgical management. PMID- 27376431 TI - A complicated case of primary hypophysitis with bilateral intracavernous carotid artery occlusion. AB - Primary hypophysitis (PH) is a rare clinical entity characterized by inflammatory infiltration of the pituitary gland with various degrees of pituitary dysfunction. OBJECTIVE: To present a complicated case of aggressive PH with bilateral cavernous sinuses infiltration, successfully treated with azathioprine after failure of corticosteroid treatment. METHODS AND RESULTS: A 48-year-old woman presented with episodes of recurrent headache and progressively worsening muscle weakness. Magnetic resonance imaging (MRI) identified an intrasellar pituitary lesion with thickened pituitary stalk extending to the cavernous sinuses and causing asymptomatic occlusion of both internal carotid arteries (ICAs). Hormonal investigation showed severe anterior pituitary deficiency. The diagnosis of PH, and more specifically of lymphocytic hypophysitis (LYH), was suspected and glucocorticoid treatment was initiated. Because of the patient's susceptibility to infections, the attempt to gradually reduce glucocorticoid dosage induced a relapse of PH. Immunosuppressive therapy with azathioprine was administered. Significant pituitary mass reduction with regression of the inflammation to the cavernous sinuses was documented. At follow-up the pituitary function was normal, while the patient was on the minimum dose of azathioprine. Thereafter, azathioprine was discontinued without any clinical/biochemical or radiological evidence of PH except for the permanent ICA occlusion. CONCLUSIONS: Despite its rarity, PH should be included in the differential diagnosis of pituitary masses and involvement of ICAs occlusion should not be underestimated. Azathioprine, applied as an alternative treatment, was shown to result in remarkable PH improvement. PMID- 27376432 TI - A case of dyskeratosis congenita associated with hypothyroidism and hypogonadism. PMID- 27376433 TI - A novel CYP11B1 mutation in a Turkish patient with 11beta-hydroxylase deficiency: An association with the severe hypokalemia leading to rhabdomyolysis. PMID- 27376434 TI - A case of multiple immune toxicities from Ipilimumab and pembrolizumab treatment. PMID- 27376436 TI - Egg collagen content is increased by a diet supplemented with wood charcoal powder containing wood vinegar liquid. AB - The aims of the present study were to examine whether collagen exists in egg, particularly in egg yolk; to establish a Fourier transform-near infrared (FT-NIR) measurement method for collagen in egg and to assess the possibility of increasing the collagen content by feeding hens a diet containing wood charcoal powder containing wood vinegar liquid (WCV). The collagen in eggs from 67-week old hens fed on the dietary 0 and 9.9 g/kg WCV diets was investigated using a combination of histochemical, matrix-assisted laser desorption ionisation with time-of-flight mass spectrometry (MALDI-TOF MS), Fourier transform infrared (FT IR) and FT-NIR approaches. All approaches used to identify collagen in egg yolk yielded positive results. The collagen in egg yolk measured using colorimetry, collagen in egg yolk, egg white and eggshell membrane using FT-NIR and collagen in egg yolk determined by treating the egg yolk with collagenase were abundant after feeding a dietary WCV (p<0.05). These results suggest that egg yolk contains collagen, that the collagen in egg can be measured using FT-NIR, and that the collagen content of egg yolk can be increased by feeding dietary WCV diets. PMID- 27376437 TI - Cancer screening education: can it change knowledge and attitudes among culturally and linguistically diverse communities in Queensland, Australia? AB - Issue addressed: Screening for cancer of the cervix, breast and bowel can reduce morbidity and mortality. Low participation rates in cancer screening have been identified among migrant communities internationally. Attempting to improve low rates of cancer screening, the Ethnic Communities Council of Queensland developed a pilot Cancer Screening Education Program for breast, bowel and cervical cancer. This study determines the impact of education sessions on knowledge, attitudes and intentions to participate in screening for culturally and linguistically diverse (CALD) communities living in Brisbane, Queensland.Methods: Seven CALD groups (Arabic-speaking, Bosnian, South Asian (including Indian and Bhutanese), Samoan and Pacific Island, Spanish-speaking, Sudanese and Vietnamese) participated in a culturally-tailored cancer screening education pilot program that was developed using the Health Belief Model. A pre- and post-education evaluation session measured changes in knowledge, attitudes and intention related to breast, bowel and cervical cancer and screening. The evaluation focussed on perceived susceptibility, perceived seriousness and the target population's beliefs about reducing risk by cancer screening.Results: There were 159 participants in the three cancer screening education sessions. Overall participants' knowledge increased, some attitudes toward participation in cancer screening became more positive and intent to participate in future screening increased (n=146).Conclusion: These results indicate the importance of developing screening approaches that address the barriers to participation among CALD communities and that a culturally-tailored education program is effective in improving knowledge, attitudes about and intentions to participate in cancer screening.So what?: It is important that culturally-tailored programs are developed in conjunction with communities to improve health outcomes. PMID- 27376435 TI - Methylphenidate-triggered ROS generation promotes caveolae-mediated transcytosis via Rac1 signaling and c-Src-dependent caveolin-1 phosphorylation in human brain endothelial cells. AB - Methylphenidate (MPH) is an amphetamine-like stimulant commonly prescribed for attention deficit hyperactivity disorder. Despite its widespread use, the cellular/molecular effects of MPH remain elusive. Here, we report a novel direct role of MPH on the regulation of macromolecular flux through human brain endothelial cells (ECs). MPH significantly increased caveolae-mediated transcytosis of horseradish peroxidase through ECs without affecting paracellular permeability. Using FRET-based live cell imaging, together with pharmacological inhibitors and lentiviral-mediated shRNA knockdown, we demonstrate that MPH promoted ROS generation via activation of Rac1-dependent NADPH oxidase (NOX) and c-Src activation at the plasma membrane. c-Src in turn was shown to mediate the phosphorylation of caveolin-1 (Cav1) on Tyr14 leading to enhanced caveolae formation and transendothelial transport. Accordingly, the inhibition of Cav1 phosphorylation by overexpression of a phosphodefective Cav1Y14F mutant or knocking down Cav1 expression abrogated MPH-induced transcytosis. In addition, both vitamin C and inhibition of NOX blocked MPH-triggered vesicular transport. This study, therefore, identifies Rac1/NOX/c-Src-dependent signaling in MPH induced increase in transendothelial permeability of brain endothelial cell monolayers via caveolae-mediated transcytosis. PMID- 27376438 TI - Brainstem micro-abscesses caused by Burkholderia pseudomallei in a 10-month-old infant: a case report. AB - Melioidosis is an uncommon tropical infectious disease caused by Burkholderia pseudomallei. Neurological complications of melioidosis are extremely uncommon in infants. A 10-month-old girl is described who presented with disseminated melioidosis with subcutaneous nodules, arthritis, hepatomegaly and a lung cavity, and developed a left medial rectus palsy. Cranial MRI demonstrated mid-brain, pontine and basal ganglia micro-abscesses. Therapy with meropenem and cotrimoxazole led to resolution of the medial nerve palsy. At 5-month follow-up, the child had no residual neurological deficits. PMID- 27376439 TI - Deep tissue biopsy vs. superficial swab culture, including microbial loading determination, in the microbiological assessment of Skin and Soft Tissue Infections (SSTIs). AB - Thirty-two patients affected by SSTIs including DFIs were enrolled between 2013 and 2014. Superficial swab was obtained before and after cleansing with sterile saline, and after ultrasonic debridement; deep tissue biopsy was obtained from ulcer base. Samples were diluted with 1 mL of saline, serial 10-fold dilutions to 10-6 were made and 50 MUL of each dilution was plated onto appropriate media. Bacteria were identified by Vitek II system. Microbial load was expressed as CFU/mL. Statistical analysis was performed by chi2. Incidence of Gram positives was higher than Gram negatives (S. aureus and P. aeruginosa being the most frequent); concordance (same bacteria isolated before and after debridement) never exceeded 60%. Ultrasonic debridement significantly reduced bacterial load or even suppressed bacterial growth. While reliability of superficial swab is poor for microbiological diagnosis of SSTIs, swabbing after ultrasonic debridement and biopsy of the ulcer base may be equally reliable. PMID- 27376440 TI - A novel paediatric thumb web splint. PMID- 27376441 TI - Avoiding iatrogenic injury during portal placement in hip arthroscopy. PMID- 27376442 TI - Wrist function in malunion: Is the distal radius designed to retain function in the face of fracture? AB - Introduction Fractures of the distal radius are the most common fracture in humans and are the sempiternal hazard of 3.5 million years of bipedalism. Despite the antiquity of the injury, one of the most controversial topics in current orthopaedics is the management of distal radius fractures. It has been suggested that radiographic appearances rarely correlate with functional outcomes. As the success of the human species is predicated almost exclusively on its dexterity and intelligence, it is conceivable that the distal radius has evolved to preserve function even in the face of injury. We therefore hypothesise that the distal radius is designed to accommodate the possibility of fracture. Methods We conducted a review of studies comparing fracture pattern and form with function. We also explore the paleoanthropological evidence and comparative studies with other primates. Findings The evidence points to the human distal radius being highly tolerant of post-fracture deformity in terms of preservation of function. In addition, the distal radius appears to have apparently anatomically 'redundant' features that confer this capability. We believe these phenomena to be an evolved trait that developed with bipedalism, increasing the chances of survival for a species whose success depends upon its dexterity. PMID- 27376443 TI - Use of non-absorbable nasal packs as a platform for microvascular anastomosis. PMID- 27376444 TI - Enhanced recovery after surgery: An opportunity to improve fractured neck of femur management. AB - Introduction Approximately 67,000 hip fractures occurred in England, Wales and Northern Ireland in 2014, and annual hospital costs for fracture are around L1.1 billion. We review the potential scope for improving length of stay (LOS). Methods Hospital Episode Statistics data on non-elective admissions to 137 hospital trusts between November 2013 and October 2015 with a primary diagnosis of fractured neck of femur were analysed. The primary outcome was superspell LOS, which is the total LOS for all related spells for a single patient during an episode of care. Secondary outcomes were discharge to home, readmission at 28 days and in-hospital mortality. Results The mean observed LOS was 22.1+/-3.8 days (range 12.3-33.7 days). The range for case mix-adjusted expected LOS was 21.5 24.4 days. On average, 6.7+/-1.5% (range 3.6%-10.9%) of patients died while in hospital, at a relative risk of in-hospital mortality of 28.2-182.9. A mean of 12.3+/-3.2% (range 3.9% to 23.0%) of patients were readmitted at 28 days, at a relative relative risk of 34.8-203.2. Conclusions The wide range of observed LOS in our study is unlikely to be due to the case mix, as the case mix-adjusted range of LOS is less than 3 days, but rather due to local processes and pathways. There is therefore considerable scope for quality and efficiency of care improvements in our hospitals. We propose this could be best achieved if clinicians experienced in enhanced recovery focused on FNOF pathways. PMID- 27376445 TI - Heterogeneous response to recombinant thrombomodulin by grade of sinusoidal obstructive syndrome after pediatric stem cell transplantation. PMID- 27376446 TI - Cardiac autonomic functioning is impaired among allogeneic hematopoietic stem cell transplantation survivors: a controlled study. AB - Healthy cardiac autonomic functioning (CAF) is essential for maintaining homeostasis in response to the environmental demands of everyday life. Impaired CAF is associated with higher morbidity and higher mortality. To explore CAF in survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) 1-10 years after transplant (median=4.3 years), an ambulatory assessment was performed with 104 patients, and 45 age- and gender-matched healthy controls. Heart rate (HR) and respiratory sinus arrhythmia (RSA, that is, high-frequency HR variability) were measured in a laboratory setting and during a 12-hour naturalistic period of daily life. Cancer-related fatigue was assessed by the Functional Assessment of Chronic Illness - Fatigue questionnaire; physical fitness by bicycle-ergometry VO2max. In contrast to healthy controls, 4-year post HSCT fatigue was greater in patients (P<0.0001, Cohen's d effect size [d]=1.14), and fitness was lower in patients (P<0.0001, d=1.09). In both laboratory and real life ambulatory conditions, average HR was persistently higher (P<0.0001, d=0.88) and mean RSA magnitude lower (P<0.001, d=0.69) among patients, compared with controls. Severely fatigued patients showed higher HR and lower parasympathetic cardiac control than non-fatigued patients (HR: P=0.02, d=0.47; RSA: P=0.02, d=0.72), and this was unrelated to fitness. These findings may have important implications for predicting long-term treatment outcome and consequences for routine post-HSCT care. PMID- 27376447 TI - Autologous stem cell transplant for multiple myeloma patients 70 years or older. AB - Autologous stem cell transplant (Auto-SCT) is increasingly used in older patients with multiple myeloma (MM), despite lack of phase 3 trials in this age-defined population. For 207 consecutive MM patients who underwent Auto-SCT and were 70 years or older at transplant (study cohort), data were analyzed and compared with a younger cohort (1764 Auto-SCT patients <70 years old). The proportion of Auto SCT in the older patients increased from 7.8% of all transplants in 1998-2006 to 12.9% in 2007-2015. Sixty percent of patients required stem cell mobilization with chemotherapy or plerixafor. Full-dose melphalan conditioning was given to 55% of the older patients compared with 93% of the younger patients (P<0.001). Older patients were more likely to be hospitalized (64% vs 55%; P=0.01), but hospitalization duration was comparable. For newly diagnosed patients, median PFS was 33.5 months for the older cohort and 33.8 months for the younger cohort (P=0.91), and median overall survival was 6.1 and 7.8 years, respectively (P=0.11). Presumably, a smaller fraction of patients, age 70-76, is selected for Auto-SCT, but the benefits are comparable to those seen for younger patients. Reduced-dose melphalan was given to approximately half the patients to avoid excessive toxicity. PMID- 27376448 TI - Haploidentical transplantation with post-transplant cyclophosphamide following reduced-intensity conditioning for osteopetrosis: outcomes in three children. PMID- 27376449 TI - Thirty years of Bone Marrow Transplantation. PMID- 27376450 TI - Differences in stem cell transplantation activity among regions in Spain: an economic explanation. PMID- 27376451 TI - Bacterial meningitis in hematopoietic stem cell transplant recipients: a population-based prospective study. AB - We performed a nationwide prospective cohort study on the epidemiology and clinical features of community-acquired bacterial meningitis. Patients with a medical history of autologous or allogeneic hematopoietic stem cell transplantation (HSCT) were identified from the cohort performed from March 2006 to October 2014. Fourteen of 1449 episodes (1.0%) of bacterial meningitis occurred in patients with a history of HSCT. The incidence of bacterial meningitis in HSCT recipients was 40.4 per 100 000 patients per year (95% confidence interval (CI) 23.9-62.2), which is 30-fold (95% CI 18-51; P<0.001) higher compared with persons without HSCT. Incidence was higher in allogeneic HSCT compared with autologous HSCT (70.0 vs 15.8 per 100 000 patients per year). Causative organisms were Streptococcus pneumoniae in 11 patients, Neisseria meningitidis in two and Streptococcus mitis in one patient. Mortality was 3 of 14 (21%) and 6 of 11 (55%) survivors had sequelae. Nine of 11 patients (82%) with pneumococcal meningitis were infected with a serotype included in the 23-valent pneumococcal polysaccharide vaccine, of whom four developed meningitis despite vaccination. In conclusion, HSCT recipients have a substantially increased risk compared with the general population of acquiring bacterial meningitis, which is mostly due to S. pneumoniae, and disease is associated with high mortality and morbidity. Vaccination is important to prevent disease although vaccine failures did occur. PMID- 27376452 TI - Dexamethasone palmitate for patients with engraftment syndrome is associated with favorable outcome for children with hematological malignancy. PMID- 27376453 TI - Clinical separation of cGvHD and GvL and better GvHD-free/relapse-free survival (GRFS) after unrelated cord blood transplantation for AML. AB - Few studies have presented a comparison of myeloablative cord blood transplantation (CBT) and HLA-identical sibling hematopoietic cell transplantation (HCT) for AML in a disease-specific analysis, and the evaluation of GvHD-free and relapse-free survival (GRFS) in AML patients after unrelated CBT has not been reported. A total of 162 consecutive AML patients receiving intensified myeloablative unrelated CBT (n=107) or allogeneic PBSC transplantation (allo-PBSCT) or bone marrow transplantation (BMT) from an HLA identical sibling donor (n=55) were investigated. Neutrophil or platelet engraftment was slower in the CBT cohort compared with that in the allo-PBSCT/BMT cohort. The incidence of grade II-IV or grade III-IV acute GvHD (aGvHD) and transplant-related mortality (TRM) were not significantly different in the two cohorts. Compared with the allo-PBSCT/BMT cohort, the CBT cohort had a significantly lower rate of chronic GvHD (cGvHD) (13.7% vs 28.3%; P=0.047) or extensive cGvHD (9.9% vs 24.1%; hazard ratio (HR)=2.06, P=0.039). The incidence of relapse at 5 years in the CBT cohort was significantly lower than that in the allo-PBSCT/BMT cohort (15.3% vs 36.1%; HR=4.62, P=0.009). The probabilities of overall survival and leukemia-free survival were similar between the two cohorts. The adjusted 5-year probability of GRFS was higher after CBT than that after allo PBSCT/BMT (55.4% vs 39.2%; HR=1.63, P=0.042). The present study suggests that, for AML patients, intensified myeloablative unrelated CBT is associated with less cGvHD and a lower risk of relapse. In addition, these patients do not experience excessive TRM or severe aGvHD that translates into better GRFS compared with those patients who undergo HLA-identical sibling allo-PBSCT/BMT; this observation may reflect the clinical separation between cGvHD and GvL within our CBT protocol. PMID- 27376454 TI - Childhood multi-drug resistant tuberculosis with paradoxical granulomas - role of steroids. PMID- 27376455 TI - Adjustable thermal resistor by reversibly folding a graphene sheet. AB - Phononic (thermal) devices such as thermal diodes, thermal transistors, thermal logic gates, and thermal memories have been studied intensively. However, tunable thermal resistors have not been demonstrated yet. Here, we propose an instantaneously adjustable thermal resistor based on folded graphene. Through theoretical analysis and molecular dynamics simulations, we study the phonon folding scattering effect and the dependence of thermal resistivity on the length between two folds and the overall length. Furthermore, we discuss the possibility of realizing instantaneously adjustable thermal resistors in experiment. Our studies bring new insights into designing thermal resistors and understanding the thermal modulation of 2D materials by adjusting basic structure parameters. PMID- 27376456 TI - Detection and treatment of Trypanosoma cruzi: a patent review (2011-2015). AB - INTRODUCTION: Trypanosoma cruzi is the etiologic agent of American trypanosomiasis (Chagas disease), which is one of the important parasitic diseases worldwide. The number of infected people with T. cruzi diminished from 18 million in 1991 to 6 million in 2010, but it is still the most prevalent parasitic disease in the Americas. The existing chemotherapy is still deficient and based on two drugs: nifurtimox and benznidazole, which are not FDA-approved in the United States. AREAS COVERED: This review covers the current and future directions of Chagas disease chemotherapy based on drugs that interfere with relevant metabolic pathways. This article also illustrates the challenges of diagnosis, which in recent infections, is only detected when the parasitemia is high (direct detection); whereas, in the chronic phase is reached after multiple serological tests. EXPERT OPINION: The current chemotherapy is associated with long term treatments and severe side effects. Nifurtimox and benznidazole are able to cure at least 50% of recent infections. Nevertheless, they suffer from major drawbacks: selective drug sensitivity on different T. cruzi strains and serious side effects. The aim of this review is focused on presenting an up-to date status of the chemotherapy and diagnosis. PMID- 27376457 TI - Clinical study of contrast-enhanced digital mammography and the evaluation of blood and lymphatic microvessel density. AB - OBJECTIVE: To correlate image parameters in contrast-enhanced digital mammography (CEDM) with blood and lymphatic microvessel density (MVD). METHODS: 18 Breast Imaging-Reporting and Data System (BI-RADS)-4 to BI-RADS-5 patients were subjected to CEDM. Craniocaudal views were acquired, two views (low and high energy) before iodine contrast medium (CM) injection and four views (high energy) 1-5 min afterwards. Processing included registration and two subtraction modalities, traditional single-energy temporal (high-energy) and "dual-energy temporal with a matrix", proposed to improve lesion conspicuity. Images were calibrated into iodine thickness, and iodine uptake, contrast, time-intensity and time-contrast kinetic curves were quantified. Image indicators were compared with MVD evaluated by anti-CD105 and anti-podoplanin (D2-40) immunohistochemistry. RESULTS: 11 lesions were cancerous and 7 were benign. CEDM subtraction strongly increased conspicuity of lesions enhanced by iodine uptake. A strong correlation was observed between lymphatic vessels and blood vessels; all benign lesions had <30 blood microvessels per field, and all cancers had more than this value. MVD showed no correlation with iodine uptake, nor with contrast. The most frequent curve was early uptake followed by plateau for uptake and contrast in benign and malignant lesions. The positive-predictive value of uptake dynamics was 73% and that of contrast was 64%. CONCLUSION: CEDM increased lesion visibility and showed additional features compared with conventional mammography. Lack of correlation between image parameters and MVD is probably due to tumour tissue heterogeneity, mammography projective nature and/or dependence of extracellular iodine irrigation on tissue composition. ADVANCES IN KNOWLEDGE: Quantitative analysis of CEDM images was performed. Image parameters and MVD showed no correlation. Probably, this is indication of the complex dependence of CM perfusion on tumour microenvironment. PMID- 27376458 TI - Elective single embryo transfer in women less than age 38 years reduces multiple birth rates, but not live birth rates, in United States fertility clinics. AB - OBJECTIVE: To determine the effect of elective single ET (eSET) on live birth and multiple birth rates by a cycle-level and clinic-level analysis. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): Patient ages <35 and 35-37 years old. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinics were divided into groups based on eSET rate for each age group and aggregate rates of live birth per ET and multiple birth per delivery were calculated. A cycle-level analysis comparing eSET and double ET (DET) live birth and multiple birth rates was also performed, stratified based on total number (2, 3, or 4+) of embryos available, embryo stage, and patient age. RESULT(S): There was a linear decrease in multiple birth rate with increasing eSET rate and no significant difference in clinic-level live birth rates for each age group. Cycle-level analysis found slightly higher live birth rates with double ET, but this was mainly observed in women aged 35-37 years or with four or more embryos available for transfer, and confirmed the marked reduction in multiple births with eSET. CONCLUSION(S): Our study showed a marked and linear reduction in multiple birth rates, and important, little to no effect on clinic-level live birth rates with increasing rates of eSET supporting the growing evidence that eSET is effective in decreasing the high multiple birth rates associated with IVF and suggests that eSET should be used more frequently than is currently practiced. PMID- 27376459 TI - Antidepressants detection and quantification in whole blood samples by GC-MS/MS, for forensic purposes. AB - Depression is among the most prevalent psychiatric disorders of our society, leading to an increase in antidepressant drug consumption that needs to be accurately determined in whole blood samples in Forensic Toxicology Laboratories. For this purpose, this work presents a new gas chromatography tandem mass spectrometry (GC-MS/MS) method targeting the simultaneous and rapid determination of 14 common Antidepressants in whole blood: 13 Antidepressants (amitriptyline, citalopram, clomipramine, dothiepin, fluoxetine, imipramine, mianserin, mirtazapine, nortryptiline, paroxetine, sertraline, trimipramine and venlafaxine) and 1 Metabolite (N-desmethylclomipramine). Solid-phase extraction was used prior to chromatographic separation. Chromatographic and MS/MS parameters were selected to improve sensitivity, peak resolution and unequivocal identification of the eluted analyte. The detection was performed on a triple quadrupole tandem MS in selected ion monitoring (SIM) mode in tandem, using electronic impact ionization. Clomipramine-D3 and trimipramine-D3 were used as deutered internal standards. The validation parameters included linearity, limits of detection, lower limit of quantification, selectivity/specificity, extraction efficiency, carry-over, precision and robustness, and followed internationally accepted guidelines. Limits of quantification and detection were lower than therapeutic and sub therapeutic concentration ranges. Overall, the method offered good selectivity, robustness and quick response (<16min) for typical concentration ranges, both for therapeutic and lethal levels. PMID- 27376460 TI - Synthesis, anti-inflammatory, analgesic, 5-lipoxygenase (5-LOX) inhibition activities, and molecular docking study of 7-substituted coumarin derivatives. AB - In the present study, 7-subsituted coumarin derivatives were synthesized using various aromatic and heterocyclic amines, and evaluated in vivo for anti inflammatory and analgesic activity, and for ulcerogenic risk. The most active compounds were evaluated in vitro for 5-lipoxygenase (5-LOX) inhibition. Docking study was performed to predict the binding affinity, and orientation at the active site of the enzyme. In vivo anti-inflammatory and analgesic activity, and in vitro 5-LOX enzyme inhibition study revealed that compound 33 and 35 are the most potent compounds in all the screening methods. In vitro kinetic study of 35 showed mixed or non-competitive type of inhibition with 5-LOX enzyme. Presence of OCH3 group in 35 and Cl in 33 at C6-position of benzothiazole ring were found very important substitutions for potent activity. PMID- 27376461 TI - Frustration and chiral orderings in correlated electron systems. AB - The term frustration refers to lattice systems whose ground state cannot simultaneously satisfy all the interactions. Frustration is an important property of correlated electron systems, which stems from the sign of loop products (similar to Wilson products) of interactions on a lattice. It was early recognized that geometric frustration can produce rather exotic physical behaviors, such as macroscopic ground state degeneracy and helimagnetism. The interest in frustrated systems was renewed two decades later in the context of spin glasses and the emergence of magnetic superstructures. In particular, Phil Anderson's proposal of a quantum spin liquid ground state for a two-dimensional lattice S = 1/2 Heisenberg magnet generated a very active line of research that still continues. As a result of these early discoveries and conjectures, the study of frustrated models and materials exploded over the last two decades. Besides the large efforts triggered by the search of quantum spin liquids, it was also recognized that frustration plays a crucial role in a vast spectrum of physical phenomena arising from correlated electron materials. Here we review some of these phenomena with particular emphasis on the stabilization of chiral liquids and non-coplanar magnetic orderings. In particular, we focus on the ubiquitous interplay between magnetic and charge degrees of freedom in frustrated correlated electron systems and on the role of anisotropy. We demonstrate that these basic ingredients lead to exotic phenomena, such as, charge effects in Mott insulators, the stabilization of single magnetic vortices, as well as vortex and skyrmion crystals, and the emergence of different types of chiral liquids. In particular, these orderings appear more naturally in itinerant magnets with the potential of inducing a very large anomalous Hall effect. PMID- 27376462 TI - Role of sequence evolution and conformational dynamics in the substrate specificity and oligomerization mode of thymidylate kinases. AB - Thymidylate kinase (TMK) is a key enzyme for the synthesis of DNA, making it an important target for the development of anticancer, antibacterial, and antiparasitic drugs. TMK homologs exhibit significant variations in sequence, residue conformation, substrate specificity, and oligomerization mode. However, the influence of sequence evolution and conformational dynamics on its quaternary structure and function has not been studied before. Based on extensive sequence and structure analyses, our study detected several non-conserved residues which are linked by co-evolution and are implicated in the observed variations in flexibility, oligomeric assembly, and substrate specificity among the homologs. These lead to differences in the pattern of interactions at the active site in TMKs of different specificity. The method was further tested on TMK from Sulfolobus tokodaii (StTMK) which has substantial differences in sequence and structure compared to other TMKs. Our analyses pointed to a more flexible dTMP binding site in StTMK compared to the other homologs. Binding assays proved that the protein can accommodate both purine and pyrimidine nucleotides at the dTMP binding site with comparable affinity. Additionally, the residues responsible for the narrow specificity of Brugia malayi TMK, whose three-dimensional structure is unavailable, were detected. Our study provides a residue-level understanding of the differences observed among TMK homologs in previous experiments. It also illustrates the correlation among sequence evolution, conformational dynamics, oligomerization mode, and substrate recognition in TMKs and detects co-evolving residues that affect binding, which should be taken into account while designing novel inhibitors. PMID- 27376463 TI - Visible light photo catalytic inactivation of bacteria and photo degradation of methylene blue with Ag/TiO2 nanocomposite prepared by a novel method. AB - Water purification is one of the worldwide problem and most of the conventional methods are associated with a number of drawbacks. Therefore it is the need of the day to develop new methods and materials to overcome the problem of water purification. In this research work we present a simple and green approach to synthesize silver decorated titanium dioxide (Ag/TiO2) nanocomposite with an efficient photo catalytic activities. Phytochemicals of the Cestrum nocturnum leaf extract were used to synthesize silver nanoparticles (AgNPs), Titanium dioxide (TiO2) and Ag/TiO2 nanocomposite. To confirm the formation, crystal structure, particle size and shape of green synthesized nanoparticles and nanocomposite, they were characterized by UV-visible spectroscopy (UV-vis), X-ray diffraction spectroscopy (XRD), high resolution transmission electron microscopy (HRTEM), Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). The AgNPs, TiO2 and Ag/TiO2 were evaluated for photo degradation of methylene blue (MB) and photo inhibition of Bacteria. The bio synthesized Ag/TiO2 nanocomposite was observed to have strong catalytic activities for photo reduction of MB and photo inactivation of bacteria as compared to bare AgNPs and TiO2. In the presence of Ag/TiO2, 90% of MB was degraded only in 40min of irradiation. Alternatively the bare AgNPs and TiO2 degraded less than 30% and 80% respectively of MB even in more than 100min of irradiation. Similarly the Ag/TiO2 has very strong photo inhibition efficiency towards Escherichia coli and Pseudomonas aeruginosa. The zone of inhibition of irradiated Ag/TiO2 nanocomposites against E. coli and P. aeruginosa was 19mm and 17mm respectively which was two times higher than in dark. These promising photocatalytic activities of nanocomposite may be due to the highly decorated AgNPs over the surface of TiO2. PMID- 27376464 TI - An estimate of the prevalence of developmental phonagnosia. AB - A web-based survey estimated the distribution of voice recognition abilities with a focus on determining the prevalence of developmental phonagnosia, the inability to identify a familiar person based on their voice. Participants matched clips of 50 celebrity voices to 1-4 named headshots of celebrities whose voices they had previously rated for familiarity. Given a strong correlation between rated familiarity and recognition performance, a residual was calculated based on the average familiarity rating on each trial, which thus constituted each respondent's voice recognition ability that could not be accounted for by familiarity. 3.2% of the respondents (23 of 730 participants) had residual recognition scores 2.28 SDs below the mean (whereas 8 or 1.1% would have been expected from a normal distribution). They also judged whether they could imagine the voice of five familiar celebrities. Individuals who had difficulty in imagining voices were also generally below average in their accuracy of recognition. PMID- 27376465 TI - In vitro antioxidant activity of rice protein affected by alkaline degree and gastrointestinal protease digestion. AB - BACKGROUND: To elucidate whether and how alkali treatment, which is a common process for rice protein (RP) extraction, affects antioxidant activity of RP, the different degree of alkali (from 0.1% to 0.4% of NaOH) was used to extract RP (RP 1, RP-2, RP-3, RP-4). RESULTS: The antioxidant capacities of scavenging free radicals [2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid] diammonium salt, ABTS; 1,1-diphenyl-2-picrylhydrazyl, DPPH), chelating metals (iron, copper) and reducing power investigated in the hydrolysates of RPs (RP-1, RP-2, RP-3, RP-4) during in vitro pepsin-pancreatin digestion were effectively affected by alkali treatment. The present study demonstrated that the weakest antioxidant responses to ABTS radical-scavenging activity, DPPH radical-scavenging activity, iron chelating activity, copper chelating activity and reducing power were produced by RP-4 extracted by the highest alkali proportion (0.4% NaOH). CONCULSION: The present study indicates that antioxidant capacity of RP could be more readily depressed by strict alkali degree and affected by gastrointestinal proteases. Results suggest that alkali extraction is a vital process to regulate the antioxidant activity of RP through modifying the compositions of amino acids, which are dependent on alkali magnitude. (c) 2016 Society of Chemical Industry. PMID- 27376467 TI - Electrochemical exfoliation of carbon dots with the narrowest full width at half maximum in their fluorescence spectra in the ultraviolet region using only water as electrolyte. AB - Here, a novel kind of CDs were electrochemically exfoliated from graphite rods using distilled water as the only electrolyte. The as-exfoliated CDs showed two significant features: the narrowest fluorescence spectra with a FWHM of only 10 nm and ultraviolet fluorescence spectra in the region up to 360 nm. PMID- 27376466 TI - TNF-alpha inhibitors reduce the pathological Th1 -Th17 /Th2 imbalance in cutaneous mesenchymal stem cells of psoriasis patients. AB - Psoriasis is a disease characterized by an imbalance between Th1 and Th17 and Th2 inflammatory axes, in which cutaneous mesenchymal stem cells (MSCs) are early involved, as they show a greater relative expression of several genes encoding for Th1 and Th17 cytokines. Therapeutic implications of TNF-alpha inhibitors on differentiated skin cells have been largely described in psoriasis; however, their effects on MSCs derived from patients with psoriasis have been only partially described. The aim of this work was to evaluate the effect of TNF-alpha inhibitors on cytokine milieu expressed by MSCs isolated from the skin of patients with psoriasis. Resident MSCs from skin of patients with psoriasis and healthy subjects have been isolated, characterized and profiled by PCR and ELISA for the expression of 22 cytokines involved in Th1 , Th2 and Th17 pathways, both before and after 12 weeks therapy with TNF-alpha inhibitors. The administration of TNF-alpha inhibitors for 12-weeks acts on MSCs as follows: it reduces the expression of several Th1 -Th17 cytokines whose levels are elevated at baseline (IL-6, IL-8, IL-12, IL-23A, IFN-gamma, TNF-alpha, CCL2, CCL20, CXCL2, CXCL5, IL 17A, IL-17C, IL-17F, IL-21, G-CSF). Similarly, it enhances the expression of several Th2 cytokines which are underexpressed at baseline (IL-2, IL-4, IL-5), reducing the expression of those overexpressed at baseline (TGF-beta and IL-13). TNF-alpha inhibitors could contribute to reduce the pathological imbalance between the Th1 -Th17 vs Th2 axis in MSCs of patients with psoriasis. PMID- 27376468 TI - Indium-Free Fully Transparent Electronics Deposited Entirely by Atomic Layer Deposition. AB - Indium-free, fully transparent thin-film transistors are fabricated entirely by the atomic layer deposition technique on rigid and flexible substrates at a low temperature of 160 degrees C. The transistors show high saturation mobility, large switching ratio, and small subthreshold swing value. The inverters and ring oscillators show large gain value and small propagation delay time, indicating the potential of this process in transparent electronic devices. PMID- 27376469 TI - Activin A programs the differentiation of human TFH cells. AB - Follicular helper T cells (TFH cells) are CD4(+) T cells specialized in helping B cells and are associated both with protective antibody responses and autoimmune diseases. The promise of targeting TFH cells therapeutically has been limited by fragmentary understanding of extrinsic signals that regulate the differentiation of human TFH cells. A screen of a human protein library identified activin A as a potent regulator of TFH cell differentiation. Activin A orchestrated the expression of multiple genes associated with the TFH program, independently or in concert with additional signals. TFH cell programming by activin A was antagonized by the cytokine IL-2. Activin A's ability to drive TFH cell differentiation in vitro was conserved in non-human primates but not in mice. Finally, activin-A-induced TFH programming was dependent on signaling via SMAD2 and SMAD3 and was blocked by pharmacological inhibitors. PMID- 27376470 TI - Asynchronous combinatorial action of four regulatory factors activates Bcl11b for T cell commitment. AB - During T cell development, multipotent progenitors relinquish competence for other fates and commit to the T cell lineage by turning on Bcl11b, which encodes a transcription factor. To clarify lineage commitment mechanisms, we followed developing T cells at the single-cell level using Bcl11b knock-in fluorescent reporter mice. Notch signaling and Notch-activated transcription factors collaborate to activate Bcl11b expression irrespectively of Notch-dependent proliferation. These inputs work via three distinct, asynchronous mechanisms: an early locus 'poising' function dependent on TCF-1 and GATA-3, a stochastic permissivity function dependent on Notch signaling, and a separate amplitude control function dependent on Runx1, a factor already present in multipotent progenitors. Despite their necessity for Bcl11b expression, these inputs act in a stage-specific manner, providing a multitiered mechanism for developmental gene regulation. PMID- 27376471 TI - CD69 controls the uptake of L-tryptophan through LAT1-CD98 and AhR-dependent secretion of IL-22 in psoriasis. AB - The activation marker CD69 is expressed by skin gammadelta T cells. Here we found that CD69 controlled the aryl hydrocarbon receptor (AhR)-dependent secretion of interleukin 22 (IL-22) by gammadelta T cells, which contributed to the development of psoriasis induced by IL-23. CD69 associated with the aromatic amino-acid-transporter complex LAT1-CD98 and regulated its surface expression and uptake of L-tryptophan (L-Trp) and the intracellular quantity of L-Trp-derived activators of AhR. In vivo administration of L-Trp, an inhibitor of AhR or IL-22 abrogated the differences between CD69-deficient mice and wild-type mice in skin inflammation. We also observed LAT1-mediated regulation of AhR activation and IL 22 secretion in circulating Vgamma9(+) gammadelta T cells of psoriatic patients. Thus, CD69 serves as a key mediator of the pathogenesis of psoriasis by controlling LAT1-CD98-mediated metabolic cues. PMID- 27376472 TI - Coccidioidomycosis Transmission Through Organ Transplantation: A Report of the OPTN Ad Hoc Disease Transmission Advisory Committee. AB - Donor-derived coccidioidomycosis has caused unexpected morbidity and mortality in transplant recipients. All proven or probable reports of donor-derived coccidioidomycosis to the Disease Transmission Advisory Committee between 2005 and August 2012 were reviewed. Six reports of proven or probable coccidioidomycosis were discovered. In four of six, the infection was first detected at autopsy in the recipient. In two cases it was first identified in the donor. Twenty-one recipients received organs from these six donors. Transmission occurred in 43% at a median of 30 days posttransplant with a mortality rate of 28.5%. Eleven recipients received preemptive antifungals, seven did not receive treatment, and treatment information was not reported for three recipients. Five of seven who did not receive prophylaxis/treatment died and all 11 who received early therapy survived. Six deaths occurred 14 to 55 days after transplant, with a median of 21 days. For exposed recipients, donor-derived coccidioidomycosis is a significant cause of morbidity and mortality. Evidence of infection in one recipient should prompt immediate evaluation for treatment of all other recipients from the same donor as preemptive treatment was effective. Further studies are needed to decide whether all donors from endemic areas should have routine serologic screening. PMID- 27376473 TI - Smaller hippocampal volumes predict lower antidepressant response/remission rates in depressed patients: A meta-analysis. AB - OBJECTIVES: Whether hippocampal volume predicts response and/or remission after antidepressant treatment of major depressive episodes (MDE) in major depressive disorder (MDD) remains unclear. We meta-analysed prospective studies comparing baseline hippocampal volume in patients with or without response/remission after antidepressant treatment. METHODS: Pubmed, Embase and Google Scholar were searched for studies of patients with current MDE in MDD, with hippocampal volume assessments at baseline, initiation of antidepressant drug treatment, and prospective assessment of response/remission after treatment. RESULTS: Six studies (374 patients), of which two were positive and four negative, were meta analysed. Compared to responders/remitters, patients who failed to achieve response/remission had smaller total hippocampus volumes at baseline (mean volume difference = 260 mm3, 95% CI [93; 427], P = 0.002). These results remained significant in patients under 60 years of age (P = 0.02), in those over 60 years old (P = 0.04), and for right (P = 0.006) and left (P = 0.02) hippocampi. The probability of non-response/non-remission was 68.6% for patients with a total hippocampal volume at least 10% lower than the average, and 47.1% for patients with a total hippocampal volume 10% higher than the average. CONCLUSIONS: In depressed patients treated with antidepressant drugs, smaller hippocampal volumes predict lower response/remission rates. PMID- 27376474 TI - Performance Characteristics and Validation of Next-Generation Sequencing for Human Leucocyte Antigen Typing. AB - High-resolution human leukocyte antigen (HLA) matching reduces graft-versus-host disease and improves overall patient survival after hematopoietic stem cell transplant. Sanger sequencing has been the gold standard for HLA typing since 1996. However, given the increasing number of new HLA alleles identified and the complexity of the HLA genes, clinical HLA typing by Sanger sequencing requires several rounds of additional testing to provide allele-level resolution. Although next-generation sequencing (NGS) is routinely used in molecular genetics, few clinical HLA laboratories use the technology. The performance characteristics of NGS HLA typing using TruSight HLA were determined using Sanger sequencing as the reference method. In total, 211 samples were analyzed with an overall accuracy of 99.8% (2954/2961) and 46 samples were analyzed for precision with 100% (368/368) reproducibility. Most discordant alleles were because of technical error rather than assay performance. More important, the ambiguity rate was 3.5% (103/2961). Seventy-four percentage of the ambiguities were within the DRB1 and DRB4 loci. HLA typing by NGS saves approximately $6000 per run when compared to Sanger sequencing. Thus, TruSight HLA assay enables high-throughput HLA typing with an accuracy, precision, ambiguity rate, and cost savings that should facilitate adoption of NGS technology in clinical HLA laboratories. PMID- 27376475 TI - Clinical Next-Generation Sequencing Pipeline Outperforms a Combined Approach Using Sanger Sequencing and Multiplex Ligation-Dependent Probe Amplification in Targeted Gene Panel Analysis. AB - Advances in next-generation sequencing (NGS) have facilitated parallel analysis of multiple genes enabling the implementation of cost-effective, rapid, and high throughput methods for the molecular diagnosis of multiple genetic conditions, including the identification of BRCA1 and BRCA2 mutations in high-risk patients for hereditary breast and ovarian cancer. We clinically validated a NGS pipeline designed to replace Sanger sequencing and multiplex ligation-dependent probe amplification analysis and to facilitate detection of sequence and copy number alterations in a single test focusing on a BRCA1/BRCA2 gene analysis panel. Our custom capture library covers 46 exons, including BRCA1 exons 2, 3, and 5 to 24 and BRCA2 exons 2 to 27, with 20 nucleotides of intronic regions both 5' and 3' of each exon. We analyzed 402 retrospective patients, with previous Sanger sequencing and multiplex ligation-dependent probe amplification results, and 240 clinical prospective patients. One-hundred eighty-three unique variants, including sequence and copy number variants, were detected in the retrospective (n = 95) and prospective (n = 88) cohorts. This standardized NGS pipeline demonstrated 100% sensitivity and 100% specificity, uniformity, and high-depth nucleotide coverage per sample (approximately 7000 reads per nucleotide). Subsequently, the NGS pipeline was applied to the analysis of larger gene panels, which have shown similar uniformity, sample-to-sample reproducibility in coverage distribution, and sensitivity and specificity for detection of sequence and copy number variants. PMID- 27376477 TI - Transport evidence for Fermi-arc-mediated chirality transfer in the Dirac semimetal Cd3As2. AB - The dispersion of charge carriers in a metal is distinctly different from that of free electrons owing to their interactions with the crystal lattice. These interactions may lead to quasiparticles mimicking the massless relativistic dynamics of high-energy particle physics, and they can twist the quantum phase of electrons into topologically non-trivial knots-producing protected surface states with anomalous electromagnetic properties. These effects intertwine in materials known as Weyl semimetals, and in their crystal-symmetry-protected analogues, Dirac semimetals. The latter show a linear electronic dispersion in three dimensions described by two copies of the Weyl equation (a theoretical description of massless relativistic fermions). At the surface of a crystal, the broken translational symmetry creates topological surface states, so-called Fermi arcs, which have no counterparts in high-energy physics or conventional condensed matter systems. Here we present Shubnikov-de Haas oscillations in focused-ion beam-prepared microstructures of Cd3As2 that are consistent with the theoretically predicted 'Weyl orbits', a kind of cyclotron motion that weaves together Fermi-arc and chiral bulk states. In contrast to conventional cyclotron orbits, this motion is driven by the transfer of chirality from one Weyl node to another, rather than momentum transfer of the Lorentz force. Our observations provide evidence for direct access to the topological properties of charge in a transport experiment, a first step towards their potential application. PMID- 27376476 TI - Dissociated functional significance of decision-related activity in the primate dorsal stream. AB - During decision making, neurons in multiple brain regions exhibit responses that are correlated with decisions. However, it remains uncertain whether or not various forms of decision-related activity are causally related to decision making. Here we address this question by recording and reversibly inactivating the lateral intraparietal (LIP) and middle temporal (MT) areas of rhesus macaques performing a motion direction discrimination task. Neurons in area LIP exhibited firing rate patterns that directly resembled the evidence accumulation process posited to govern decision making, with strong correlations between their response fluctuations and the animal's choices. Neurons in area MT, in contrast, exhibited weak correlations between their response fluctuations and choices, and had firing rate patterns consistent with their sensory role in motion encoding. The behavioural impact of pharmacological inactivation of each area was inversely related to their degree of decision-related activity: while inactivation of neurons in MT profoundly impaired psychophysical performance, inactivation in LIP had no measurable impact on decision-making performance, despite having silenced the very clusters that exhibited strong decision-related activity. Although LIP inactivation did not impair psychophysical behaviour, it did influence spatial selection and oculomotor metrics in a free-choice control task. The absence of an effect on perceptual decision making was stable over trials and sessions and was robust to changes in stimulus type and task geometry, arguing against several forms of compensation. Thus, decision-related signals in LIP do not appear to be critical for computing perceptual decisions, and may instead reflect secondary processes. Our findings highlight a dissociation between decision correlation and causation, showing that strong neuron-decision correlations do not necessarily offer direct access to the neural computations underlying decisions. PMID- 27376478 TI - Allergic-like reactions to asparaginase: Atypical allergies without asparaginase inactivation. AB - BACKGROUND: Asparaginase is an important component of pediatric acute lymphoblastic leukemia (ALL) therapy. Unfortunately, this treatment is hampered by hypersensitivity reactions. In general, allergies - regardless of severity - cause complete inactivation of the drug. However, we report atypical allergic reactions without inactivation of asparaginase, here called allergic-like reactions. PROCEDURE: Patients with an allergic-like reaction, who were treated according to the Dutch Childhood Oncology Group ALL-11 or the CoALL 08-09 protocol, were described. The reactions were identified by continual measurement of asparaginase activity levels. Characteristics, including timing of occurrence, symptoms, grade, and the presence of antiasparaginase antibodies, were compared to those of real allergies. RESULTS: Fourteen allergic-like reactions occurred in nine patients. Five reactions were to PEGasparaginase and nine to Erwinia asparaginase. Allergic-like reactions occurred relatively late after the start of infusion compared to real allergies. Antibodies were absent in all but one patient with an allergic-like reaction, while they were detected in all patients with a real allergy. Symptoms and grade did not differ between the groups. Asparaginase was continued with the same formulation in six patients of whom four finished treatment with adequate activity levels. CONCLUSIONS: In conclusion, allergic-like reactions occur relatively late after the start of infusion and without antibodies. Despite these clinical differences, allergic-like reactions can only be distinguished from real allergies by continually measuring asparaginase activity levels. If clinically tolerated, formulations should not be switched in case of allergic-like reactions. Moreover, failure to recognize these reactions may lead to a less favorable prognosis if asparaginase therapy is terminated unnecessarily. PMID- 27376479 TI - Simultaneous time course analysis of multiple markers based on DNA microarray in incised wound in skeletal muscle for wound aging. AB - Assessment of incised wound age in skeletal muscles is important because fatal injuries are often complicated with muscle involvement. Transcriptome of injured skeletal muscle along with histopathological and immunohistochemistry staining, were analyzed to explore the biological effect of incised injuries using a mouse incised injury model. An incisional wound was made at the biceps femoris muscle of anesthetized mice, and the muscles were sampled at 6, 12, 24, 36 and 48h post injury. DNA microarray analysis using RNA extracted from the muscle samples of 12h post-injury identified 3,655 upregulated and 3,583 downregulated genes. Referring to the results of the gene ontology and gene expression pathway analysis, time course expression of five cytokines, namely chemokine (C-C motif) ligand 4 (CCL4), chemokine (C-X-C motif) ligand 5 (CXCL5), interleukin-1 beta (IL 1beta), interleukin- 6 (IL-6) and interleukin-7 (IL-7), were analyzed by quantative reverse transcription PCR (qRT-PCR). CXCL5 was the most upregulated gene throughout the post-injury period with higher expression from 6 through 36h post injury. Upregulation of CCL4 and IL-1beta was also persisted until 36h post injury. IL-6 mRNA was highly and rapidly expressed at 6h post-injury followed by significant decrease at 12h. Unlike other four cytokines, IL-7 showed slow and steady increasing over time until 48h post-injury. Immunohistochemical staining of post-injury samples showed gradual mild increase of staining intensity proportional to increasing time points especially around the wound edges. The present study highlights the unique dynamics of each cytokine and reflects their roles in the process of muscle wound healing, and suggests the potential of them as a tool for forensic wound age estimation. PMID- 27376480 TI - A Bioinspired Synthesis of (+/-)-Rubrobramide, (+/-)-Flavipucine, and (+/-) Isoflavipucine. AB - A biomimetic synthesis of naturally occurring lactams rubrobramide, flavipucine, and isoflavipucine is described. The key step is a regioselective Darzens reaction between isobutyl glyoxal and an alpha-bromo-beta-ketoamide. The construction of the core tricyclic ring system of rubrobramide was achieved by a cascade reaction in a single step from an alpha,beta-epoxy-gamma-lactam. Furthermore, the absolute configuration of naturally occurring (+)-rubrobramide was determined by vibrational circular dichroism. (+/-)-Flavipucine and (+/-) isoflavipucine were synthesized from an epoxyimide, which was prepared by reaction of isobutyl glyoxal with a protected alpha-bromo-beta-ketoamide. Deprotection of the epoxyimide and formation of the pyridone ring gave (+/-) flavipucine, which was converted into (+/-)-isoflavipucine by thermal isomerization. PMID- 27376481 TI - A novel supine isocentric approach for craniospinal irradiation and its clinical outcome. AB - OBJECTIVE: To report a novel approach for craniospinal irradiation (CSI) using a supine isocentric technique. METHODS: Patients were treated in the supine position using CT simulation. Half-beam-blocked lateral cranial fields and superior spinal fields have the same isocentre, and their beam divergences match. Tangential irradiation provides a non-divergent junction for the other two full beam spinal fields. Shielding for cranial fields was generated, and dose distribution was calculated using a three-dimensional planning system. When sacral spinal fields were required, two lateral opposite fields were designed to protect the urogenital organs. All treatment portals were filmed once per week. RESULTS: At a median follow-up of 49.8 months, 5 relapses and no cases of radiation myelitis developed in 26 consecutive patients. In the junctions of the brain-spine or spine-spine field, no failure occurred. Three failures occurred in the primary site alone, two in the spinal axis alone. CONCLUSION: The results of our study have shown that our novel approach for CSI was not associated with increased failures at the field junction and deaths. In addition, no radiation myelitis, pneumonia, severe damage to the heart and gastrointestinal tract, and second cancers occurred in our study. ADVANCES IN KNOWLEDGE: This new approach is an optimal alternative in cancer centre without tomotherapy because of its convenience for immobilization, repeatability, optimal dose distribution and satisfactory clinical outcome. PMID- 27376482 TI - Cisplatin for testicular germ cell tumors: a rapid review. AB - OBJECTIVE: Cisplatin is one of efficacious medicines for TGCT, but is not in 18th WHO EML now. The Union for International Cancer Control recommended cisplatin to the 19th WHO EML for TGCT. To evaluate the effectiveness, safety and cost of cisplatin for TGCT according to the requirements of WHO EML Expert Committee, and to provide the evidence whether cisplatin should be included in WHO EML. METHOD: We searched The Cochrane Library, PubMed, EMbase, NHS EED, US National Guideline Clearinghouse (NGC) and WHO guidelines. Guidelines and systematic reviews (SRs) on cisplatin for TGCT were included. Two reviewers selected studies and extracted relevant information independently. Quality of SRs was appraised through AMSTAR. RESULTS: Seven guidelines and four SRs were included in this rapid review. Quality of SRs was moderate according to AMSTAR. The results showed that: (a) effectiveness: cisplatin-based chemotherapy significantly improved in response rates and overall survival for more advanced disease (stage II and stage III). Bleomycin, etoposide, and cisplatin (BEP)-one of the most widely used of cisplatin-based chemotherapy regimens should be considered as the standard treatment of good-prognosis patients with survival rates of 90% and as the best option for intermediate- or poor-prognosis patients with survival rates of 75% and 50%, respectively. (b) Safety: nephrotoxicity, ototoxicity and peripheral neuropathy are common adverse effects of cisplatin. (c) Cost: there was no relevant study about cost of cisplatin for TGCT. But the affordability of cispaltin is good for Chinese patients, due to it is in health insurance directory of China. CONCLUSIONS: We recommend cisplatin to be listed in 19th WHO EML for TGCT, due to adequate evidence of effectiveness and good affordability. PMID- 27376483 TI - Increased Expression of GM1 Detected by Electrospray Mass Spectrometry in Rat Primary Embryonic Cortical Neurons Exposed to Glutamate Toxicity. AB - Neurons within different brain regions have varying levels of vulnerability to external stress and respond differently to injury. A potential reason to explain this may lie within a key lipid class of the cell's plasma membrane called gangliosides. These glycosphingolipid species have been shown to play various roles in the maintenance of neuronal viability. The purpose of this study is to use electrospray ionization mass spectrometry (ESI-MS) and immunohistochemistry to evaluate the temporal expression profiles of gangliosides during the course of neurodegeneration in rat primary cortical neurons exposed to glutamate toxicity. Primary embryonic (E18) rat cortical neurons were cultured to DIV (days in vitro) 14. Glutamate toxicity was induced for 1, 3, 6, and 24 h to injure and kill neurons. Immunofluorescence was used to stain for GM1 and GM3 species, and ESI-MS was used to quantify the ganglioside species expressed within these injured neurons. ESI-MS data revealed that GM1, GM2, and GM3 were up-regulated in neurons exposed to glutamate. Interestingly, using immunofluorescence, we demonstrated that the GM1 increase following glutamate exposure occurred in viable neurons, possibly indicating a potential intrinsic neuroprotective response. To test this potential neuroprotective property, neurons were pretreated with GM1 for 24 h prior to glutamate exposure. Pretreatment with GM1 conferred significant neuroprotection against glutamate-induced cell death. Overall, work from this study validates the use of ESI-MS for cell-derived gangliosides and supports the further development of lipid based strategies to protect against neuron cell death. PMID- 27376484 TI - CLOCK-BMAL1 regulate the cardiac L-type calcium channel subunit CACNA1C through PI3K-Akt signaling pathway. AB - The heterodimerized transcription factors CLOCK-BMAL1 regulate the cardiomyocyte circadian rhythms. The L-type calcium currents play important role in the cardiac electrogenesis and arrhythmogenesis. Whether and how the CLOCK-BMAL1 regulate the cardiac L-type calcium channels are yet to be determined. The functions of the L type calcium channels were evaluated with patch clamping techniques. Recombinant adenoviruses of CLOCK and BMAL1 were used in the expression experiments. We reported that the expressions and functions of CACNA1C (the alpha-subunit of the L-type calcium channels) showed circadian rhythms, with the peak at zeitgeber time 3 (ZT3). The endocardial action potential durations 90 (APD90) were correspondingly longer at ZT3. The protein levels of the phosphorylated Akt at threonine 308 (pAkt T308) also showed circadian rhythms. Overexpressions of CLOCK BMAL1 significantly reduced the levels of CACNA1C while increasing the levels of pAkt T308 and pik3r1. Furthermore, the inhibitory effects of CLOCK-BMAL1 on CACNA1C could be abolished by the Akt inhibitor MK2206 or the PDK1 inhibitor GSK2334470. Collectively, our findings suggested that the expressions of the cardiac CACNA1C were under the CLOCK-BMAL1 regulation, probably through the PI3K Akt signal pathway. PMID- 27376485 TI - Effect of horizontal curves on urban arterial crashes. AB - The crash prediction models of the Highway Safety Manual (HSM), 2010 estimate the expected number of crashes for different facility types. Models in Part C Chapter 12 of the first edition of the HSM include crash prediction models for divided and undivided urban arterials. Each of the HSM crash prediction models for highway segments is comprised of a "Safety Performance Function," a function of AADT and segment length, plus, a series of "Crash Modification Factors" (CMFs). The SPF estimates the expected number of crashes for the site if the site features are of base condition. The effects of the other features of the site, if their values are different from base condition, are carried out through use of CMFs. The existing models for urban arterials do not have any CMF for horizontal curvature. The goal of this research is to investigate if the horizontal alignment has any significant effect on crashes on any of these types of facilities and if so, to develop a CMF for this feature. Washington State cross sectional data from the Highway Safety Information System (HSIS), 2014 was used in this research. Data from 2007 to 2009 was used to conduct the investigation. The 2010 data was used to validate the results. As the results showed, the horizontal curvature has significant safety effect on two-lane undivided urban arterials with speed limits of 35 mph and higher and using a CMF for horizontal curvature in the crash prediction model of this type of facility improves the prediction of crashes significantly, for both tangent and curve segments. PMID- 27376486 TI - Unravelling post-transcriptional PrmC-dependent regulatory mechanisms in Pseudomonas aeruginosa. AB - Transcriptional regulation has a central role in cellular adaptation processes and is well investigated. In contrast, the importance of the post-transcriptional regulation on these processes is less well defined. The technological advancements have been critical to precisely quantify protein and mRNA level changes and hold promise to provide more insights into how post-transcriptional regulation determines phenotypes. In Pseudomonas aeruginosa the methyltransferase PrmC methylates peptide chain release factors to facilitate translation termination. Loss of PrmC activity abolishes anaerobic growth and leads to reduced production of quorum sensing-associated virulence factors. Here, by applying SILAC technology in combination with mRNA-sequencing, they provide evidence that the P. aeruginosa phenotype can be attributed to a change in protein to mRNA ratios of selected protein groups. The UAG-dependent translation termination was more dependent on PrmC activity than the UAA- and UGA-dependent translation termination. Additionally, a bias toward UAG stop codons in global transcriptional regulators was found. The finding that this bias in stop codon usage determines the P. aeruginosa phenotype is unexpected and adds complexity to regulatory circuits. Via modulation of PrmC activity the bacterial cell can cross regulate targets independently of transcriptional signals, a process with an underestimated impact on the bacterial phenotype. PMID- 27376487 TI - Gene duplication and divergence produce divergent MHC genotypes without disassortative mating. AB - Genes of the major histocompatibility complex (MHC) exhibit heterozygote advantage in immune defence, which in turn can select for MHC-disassortative mate choice. However, many species lack this expected pattern of MHC-disassortative mating. A possible explanation lies in evolutionary processes following gene duplication: if two duplicated MHC genes become functionally diverged from each other, offspring will inherit diverse multilocus genotypes even under random mating. We used locus-specific primers for high-throughput sequencing of two expressed MHC Class II B genes in Leach's storm-petrels, Oceanodroma leucorhoa, and found that exon 2 alleles fall into two gene-specific monophyletic clades. We tested for disassortative vs. random mating at these two functionally diverged Class II B genes, using multiple metrics and different subsets of exon 2 sequence data. With good statistical power, we consistently found random assortment of mates at MHC. Despite random mating, birds had MHC genotypes with functionally diverged alleles, averaging 13 amino acid differences in pairwise comparisons of exon 2 alleles within individuals. To test whether this high MHC diversity in individuals is driven by evolutionary divergence of the two duplicated genes, we built a phylogenetic permutation model. The model showed that genotypic diversity was strongly impacted by sequence divergence between the most common allele of each gene, with a smaller additional impact of monophyly of the two genes. Divergence of allele sequences between genes may have reduced the benefits of actively seeking MHC-dissimilar mates, in which case the evolutionary history of duplicated genes is shaping the adaptive landscape of sexual selection. PMID- 27376488 TI - The life aquatic: advances in marine vertebrate genomics. AB - The ocean is hypothesized to be where life on earth originated, and subsequent evolutionary transitions between marine and terrestrial environments have been key events in the origin of contemporary biodiversity. Here, we review how comparative genomic approaches are an increasingly important aspect of understanding evolutionary processes, such as physiological and morphological adaptation to the diverse habitats within the marine environment. In addition, we highlight how population genomics has provided unprecedented resolution for population structuring, speciation and adaptation in marine environments, which can have a low cost of dispersal and few physical barriers to gene flow, and can thus support large populations. Building upon this work, we outline the applications of genomics tools to conservation and their relevance to assessing the wide-ranging impact of fisheries and climate change on marine species. PMID- 27376490 TI - An update on repurposed medications for the treatment of drug-resistant tuberculosis. AB - INTRODUCTION: Drug-resistant forms of tuberculosis are a major public health problem with a serious global impact. Although there have recently been two new drugs introduced for the treatment of drug-resistant TB (bedaquiline and delamanid), the current therapeutic armamentarium is limited. Because treatment of drug-resistant TB requires the use of a multidrug-regimen, there has been growing interest in the use of antibiotics developed for other infectious pathogens but that have shown efficacy in the treatment of TB. AREAS COVERED: This paper will review these 're-purposed' agents - including the beta-lactams, clarithromycin, clofazimine, the fluoroquinolones, and linezolid - with a focus on their efficacy, safety, and pharmacokinetic properties. Expert commentary: There is growing evidence on the efficacy and safety of repurposed drugs for the treatment of drug-resistant TB, supporting their program-wide inclusion in treatment regimens as recommended in revised WHO guidelines. However, additional work is needed to define optimum dosing as well as describe their role in regimen optimization. PMID- 27376491 TI - Design and synthesis of pyrimidinyl acyl thioureas as novel Hsp90 inhibitors in invasive ductal breast cancer and its bone metastasis. AB - Invasive ductal carcinoma is the most common breast malignancies tumors and has tendency to bone metastases. Many oncogenic client proteins involved in formation of metastatic pathways. Stabilization, regulation, and maintenance of these oncogenic client proteins are provided with Heat Shock Protein 90 (Hsp90). Hsp90 perform these processes through its ATP binding and subsequent hydrolysis energy. Therefore, designing Hsp90 inhibitors is a novel cancer treatment method. However, many Hsp90 inhibitors have solubility problems and showed adverse effects in clinical trials. Thus, we designed and synthesized novel pyrimidinyl acyl thiourea derivatives to selectively inhibit Hsp90 alpha in human invasive ductal breast (MCF-7) and human bone osteosarcoma (Saos-2) cell lines. In vitro experiments showed that the compounds inhibited cell proliferation, ATP hydrolysis, and exhibited cytotoxic effect on these cancer cell lines. Further, gene expression was analyzed by microarray studies on MCF-7 cell lines. Several genes that play vital roles in breast cancer pathogenesis displayed altered gene expression in the presence of a selected pyrimidinyl acyl thiourea compound. Molecular docking studies were also performed to determine interaction between Hsp90 ATPase domain and pyrimidinyl acyl thiourea derivatives. The results indicated that the compounds are able to interact with Hsp90 ATP binding pocket and inhibit ATPase function. The designed compounds powerfully inhibit Hsp90 by an average of 1 MUM inhibition constant. And further, the compounds perturb Hsp90 N terminal domain proper orientation and ATP may not provide required conformational change for Hsp90 function as evidenced by in silico experiments. Therefore, the designed compounds effectively inhibited both invasive ductal breast carcinoma and bone metastasis. Pyrimidinyl acyl thiourea derivatives may provide a drug template for effective treatment of invasive ductal breast carcinoma and its bone metastasis as well as new therapeutic perspective for drug design. PMID- 27376489 TI - Computational genomics tools for dissecting tumour-immune cell interactions. AB - Recent breakthroughs in cancer immunotherapy and decreasing costs of high throughput technologies have sparked intensive research into tumour-immune cell interactions using genomic tools. The wealth of the generated data and the added complexity pose considerable challenges and require computational tools to process, to analyse and to visualize the data. Recently, various tools have been developed and used to mine tumour immunologic and genomic data effectively and to provide novel mechanistic insights. Here, we review computational genomics tools for cancer immunology and provide information on the requirements and functionality in order to assist in the selection of tools and assembly of analytical pipelines. PMID- 27376492 TI - New, highly potent and non-toxic, chromone inhibitors of the human breast cancer resistance protein ABCG2. AB - Breast cancer resistance protein (BCRP/ABCG2) is one of the major transporters involved in the efflux of anticancer compounds, contributing to multidrug resistance (MDR). Inhibition of ABCG2-mediated transport is then considered a promising strategy for overcoming MDR in tumors. We recently identified a chromone derivative, namely MBL-II-141 as a selective ABCG2 inhibitor, with relevant in vivo activity. Here, we report the pharmacomodulation of MBL-II-141, with the aim of identifying key pharmacophoric elements to design more potent selective and non-toxic inhibitors. Through rational structural modifications of MBL-II-141, using simple and affordable chemistry, we obtained highly active and easily-made inhibitors of ABCG2. Among the investigated compounds, derivative 4a, was found to be 3-fold more potent than MBL-II-141. It was similarly efficient as the reference inhibitor Ko143 but with the advantage of a lower intrinsic cytotoxicity, and therefore constitutes the best ABCG2 inhibitor ever reported displaying a very high therapeutic ratio. PMID- 27376493 TI - Natural product-inspired rational design, synthesis and biological evaluation of 2,3-dihydropyrano[2,3-f]chromen-4(8H)-one based hybrids as potential mitochondrial apoptosis inducers. AB - Synthesis of novel pyranochromanone amide hybrids, by combining pyranochromanone pharmacophore and privileged scaffolds such as 2-amino-1,3,4-thiadiaole/2 aminothiazole/aminopyridine/aminonaphthalene and anti-cancer evaluation of a series led us to discover a series of new chemical entities (NCEs) showing broad spectrum of anti-cancer activity against three different human cancer cell lines (MCF-7, A549 and HeLa), at IC50 values ranging from 14.3 to 97.8 MUM. Among them, some compounds such as 15b, 15d, 20a and 20b displayed excellent activity against breast cancer cell line MCF-7. Detailed biological studies such as AO/EB dual staining, Hoechst 33342 staining, FACS analysis of mitochondrial membrane potential (Deltapsim) using JC-1 dye and DNA fragmentation confirmed the apoptosis induced by the hybrids. Gene expression studies by Real time RT-PCR has shown that these compounds are efficient regulator of anti-apoptotic gene Bcl-2. Western blot analysis also revealed that these compounds persuade apoptosis through intrinsic pathway by up-regulating the pro-apoptotic protein Bax and down regulating the anti-apoptotic protein Bcl-2. Molecular docking studies reveal that compounds 15b and 20b binds efficiently with Bcl-2 promoter G-quadruplex. PMID- 27376494 TI - Bicyclic octahydrocyclohepta[b]pyrrol-4(1H)one derivatives as novel selective anti-hepatitis C virus agents. AB - We report the discovery of the bicyclic octahydrocyclohepta[b]pyrrol-4(1H)-one scaffold as a new chemotype with anti-HCV activity on genotype 1b and 2a subgenomic replicons. The most potent compound 34 displayed EC50 values of 1.8 MUM and 4.5 MUM in genotype 1b and 2a, respectively, coupled with the absence of any antimetabolic effect (gt 1b SI = 112.4; gt 2a SI = 44.2) in a cell-based assay. Compound 34 did not target HCV NS5B, IRES, NS3 helicase, or selected host factors, and thus future work will involve the unique mechanism of action of these new antiviral compounds. PMID- 27376495 TI - Avarol derivatives as competitive AChE inhibitors, non hepatotoxic and neuroprotective agents for Alzheimer's disease. AB - Avarol is a marine sesquiterpenoid hydroquinone, previously isolated from the marine sponge Dysidea avara Schmidt (Dictyoceratida), with antiinflammatory, antitumor, antioxidant, antiplatelet, anti-HIV, and antipsoriatic effects. Recent findings indicate that some thio-avarol derivatives exhibit acetylcholinesterase (AChE) inhibitory activity. The multiple pharmacological properties of avarol, thio-avarol and/or their derivatives prompted us to continue the in vitro screening, focusing on their AChE inhibitory and neuroprotective effects. Due to the complex nature of Alzheimer's disease (AD), there is a renewed search for new, non hepatotoxic anticholinesterasic compounds. This paper describes the synthesis and in vitro biological evaluation of avarol-3'-thiosalicylate (TAVA) and thiosalycil-prenyl-hydroquinones (TPHs), as non hepatotoxic anticholinesterasic agents, showing a good neuroprotective effect on the decreased viability of SHSY5Y human neuroblastoma cells induced by oligomycin A/rotenone and okadaic acid. A molecular modeling study was also undertaken on the most promising molecules within the series to elucidate their AChE binding modes and in particular the role played by the carboxylate group in enzyme inhibition. Among them, TPH4, bearing a geranylgeraniol substituent, is the most significant Electrophorus electricus AChE (EeAChE) inhibitor (IC50 = 6.77 +/- 0.24 MUM), also endowed with a moderate serum horse butyrylcholinesterase (eqBuChE) inhibitory activity, being also the least hepatotoxic and the best neuroprotective compound of the series. Thus, TPHs represents a new family of synthetic compounds, chemically related to the natural compound avarol, which has been discovered for the potential treatment of AD. Findings prove the relevance of TPHs as a new possible generation of competitive AChE inhibitors pointing out the importance of the salycilic substituents on the hydroquinone ring. Since these compounds do not belong to the class of alkaloids, which are notorious for their capability to inhibit AChE while exhibiting side effects, they may constitute novel active AChE inhibitors with fewer side effects. PMID- 27376496 TI - Detailed Investigation of the Immunodominant Role of O-Antigen Stoichiometric O Acetylation as Revealed by Chemical Synthesis, Immunochemistry, Solution Conformation and STD-NMR Spectroscopy for Shigella flexneri 3a. AB - Shigella flexneri 3a causes bacillary dysentery. Its O-antigen has the {2)-[alpha d-Glcp-(1->3)]-alpha-l-Rhap-(1->2)-alpha-l-Rhap-(1->3)-[Ac->2]-alpha-l-Rhap-(1 >3)-[Ac->6]~40 % -beta-d-GlcpNAc-(1->} ([(E)ABAc CAc D]) repeating unit, and the non-O-acetylated equivalent defines S. flexneri X. Propyl hepta-, octa-, and decasaccharides sharing the (E')A'BAc CD(E)A sequence, and their non-O-acetylated analogues were synthesized from a fully protected BAc CD(E)A allyl glycoside. The stepwise introduction of orthogonally protected mono- and disaccharide imidate donors was followed by a two-step deprotection process. Monoclonal antibody binding to twenty-six S. flexneri types 3a and X di- to decasaccharides was studied by an inhibition enzyme-linked immunosorbent assay (ELISA) and STD-NMR spectroscopy. Epitope mapping revealed that the 2C -acetate dominated the recognition by monoclonal IgG and IgM antibodies and that the BAc CD segment was essential for binding. The glucosyl side chain contributed to a lesser extent, albeit increasingly with the chain length. Moreover, tr-NOESY analysis also showed interaction but did not reveal any meaningful conformational change upon antibody binding. PMID- 27376497 TI - Characterization of Active Dry Wine Yeast During Starter Culture (Pied de Cuve) Preparation for Sparkling Wine Production. AB - The preparation of yeast starter culture (Pied de Cuve) for producing sparkling wine with the traditional method is a key factor for manufacturing a good Prise de mousse. In this paper, the evolution of total yeast population, its viability during Pied de Cuve preparation, and the pressure profile during the 2nd fermentation in 2 different base wines made from Bombino bianco and Chardonnay grapes were investigated using 4 different commercial active dried yeasts. The study proves that despite the initial differences observed throughout the acclimatization phase, all the tested strains showed similar results on either the total population (from 8.2 * 10(7) cells/mL to 1.3 * 10(8) cells/mL) or cellular viability (from 70% to 84%). Independently from the base wine tested, the kinetic of sugar consumption was faster during the gradual acclimatization to the alcoholic medium (phase II) and slower during the preparation of starter culture in active growth phase (phase III). During both of these phases Saccharomyces cerevisiae bayanus Vitilevure DV10((r)) (Station oenotechnique de Champagne) proved to have a higher sugar consumption rate than the other strains. During the Prise de mousse, S. cerevisiae bayanus Lalvin EC-1118((r)) (Lallemand) reached the maximum pressure increase within time in both base wines. PMID- 27376498 TI - Tuning Surface Properties of Low Dimensional Materials via Strain Engineering. AB - The promising and versatile applications of low dimensional materials are largely due to their surface properties, which along with their underlying electronic structures have been well studied. However, these materials may not be directly useful for applications requiring properties other than their natal ones. In recent years, strain has been shown to be an additionally useful handle to tune the physical and chemical properties of materials by changing their geometric and electronic structures. The strategies for producing strain are summarized. Then, the electronic structure of quasi-two dimensional layered non-metallic materials (e.g., graphene, MX2, BP, Ge nanosheets) under strain are discussed. Later, the strain effects on catalytic properties of metal-catalyst loaded with strain are focused on. Both experimental and computational perspectives for dealing with strained systems are covered. Finally, an outlook on engineering surface properties utilizing strain is provided. PMID- 27376499 TI - Identification of miRNAs and their targets involved in the secondary metabolic pathways of Mentha spp. AB - The endogenous, small and non-coding functional microRNAs govern the regulatory system of gene expression and control the growth and development of the plants. Mentha spp. are well known herbs for its flavor, fragrance and medicinal properties. In the present study, we used a computational approach to identify miRNAs and their targets involved in different secondary metabolic pathways of Mentha spp. Additionally, phylogenetic and conservation analysis were also done for the predicted miRNAs. Eleven miRNAs families were identified from Mentha spp., out of which five miRNA families were reported for the first time from Lamiaceae. Overall, 130 distinct target transcripts were predicted for eight miRNAs families. All the predicted targets regulated by predicted miRNAs control the reproduction, signaling, stimulus response, developmental and different metabolic process. miRNA mediated gene regulatory network was also constructed on the basis of hybridized minimum free energy of identified miRNAs and their targets. The study revealed that the gene regulatory system of essential oil biosynthesis may be governed by miR156, miR414 and miR5021 in mint family. Furthermore, three miRNA candidates (miR156, miR5021, and miR5015b) were observed to be involved in trichome development also. This is the first in-silico study describing miRNAs and their role in the regulation of secondary metabolic pathways in Mentha spp. PMID- 27376500 TI - Implication of vector characteristics of Phlebotomus argentipes in the kala-azar elimination programme in the Indian sub-continent. AB - BACKGROUND: Visceral leishmaniasis (VL), also known as kala-azar in the Indian sub-continent (ISC), is a major public health concern in Bangladesh, India, and Nepal, where it is caused by Leishmania donovani transmitted by the sand fly Phlebotomus argentipes. Various ecological parameters including air temperature, rainfall, wind speed, relative humidity, soil moisture, pH, and organic carbon are known to influence the oviposition of female sand flies, as well as the survival and development of larvae. However, more detailed knowledge on vector behavior, such as biting times, breeding places, and preferred hosts are needed to design optimal evidence-based vector control interventions. METHODS: In order to facilitate rational decisions regarding VL vector control, a systematic review was conducted to identify the prevailing practice and knowledge gaps in relation to vector bionomics and behavior. Search terms included 'sand fly bionomics', 'habitat', and 'visceral leishmaniasis/kala-azar vector control' using the Boolean operator AND to identify the country of interest, namely: Bangladesh, India, and Nepal. Both PubMed and Google search engines were used. Additional unpublished documents in the three countries were also analyzed. RESULTS: Information on the life cycle of VL vectors, their breeding behavior, infection rate with L. donovani, feeding behavior, and seasonal variation are useful for designing vector control operations. Unfortunately, none of the studies on the life cycle of P. argentipes was conducted in field settings of the ISC, so the publications from other locations had to be used for determining the duration of life cycle and development from egg to adult. However, information about breeding places, seasonal variation of vector densities, and 47 out of the selected 51 papers are available from the ISC and can be used for intelligent design of control operations. CONCLUSION: Vector control services should undertake routine insecticide resistance monitoring and adapt indoor residual spraying rounds to the seasonality of vector densities. Further research is needed on potential animal reservoirs for L. donovani, on the breeding habitat, and life cycle of sand flies in the ISC. PMID- 27376501 TI - Mansonella ozzardi: a neglected New World filarial nematode. AB - Mansonella ozzardi (Nematoda: Onchocercidae) is an understudied filarial nematode, originally described by Patrick Manson in 1897, that can be transmitted by two families of dipteran vectors, biting midges (most of them members of the genus Culicoides) and black flies (genus Simulium). With a patchy geographic distribution from southern Mexico to northwestern Argentina, human infection with M. ozzardi is highly prevalent in some of the Caribbean islands, along riverine communities in the Amazon Basin, and on both sides of the border between Bolivia and Argentina. There is no clinical entity unequivocally associated with M. ozzardi infection, although fever, arthralgia, headache, cold lower extremities, and itchy cutaneous rashes are occasionally mentioned in case report series. More recently, ocular manifestations (especially keratitis) have been associated with mansonelliasis, opening an important area of investigation. Here, we briefly review the biology, epidemiology, pathogenesis, and clinical aspects of M. ozzardi infection and point to some existing knowledge gaps, aiming to stimulate a research agenda to help filling them. PMID- 27376502 TI - Distribution of Aedes mosquitoes in the Kilimanjaro Region of northern Tanzania. AB - Little is known about the presence and distribution of Aedes mosquitoes in northern Tanzania despite the occurence of viruses transmitted by these mosquitoes such as Chikungunya virus (CHIKV) and Dengue virus (DENV) in the region. Adult and larval mosquitoes were collected from rural and urban settings across a wide range of altitudes in the Kilimanjaro Region using the Mosquito Magnet CO2 Trap for collection of adults and old tires for breeding of larvae. Polymerase chain reaction assays were performed on captured adult mosquitoes to detect the presence of CHIKV and DENV. A total of 2609 Aedes aegypti adult mosquitoes were collected; no other Aedes species larvae were found. Mosquito yields were significantly higher in urban settings than rural settings (26.5 vs. 1.9 mosquitoes per day, p = 0.037). A total of 6570 Ae. aegypti larvae were collected from old tires; no other Aedes species larvae were found. Of the 2609 adult mosquitoes collected, none tested positive for CHIKV or DENV. As far as we are aware, this paper reports for the first time the presence of Ae. aegypti in the Kilimanjaro Region of northern Tanzania. Although CHIKV and DENV were not isolated from any of the collected mosquitoes in this study, the apparent absence of other Aedes species in the area suggests that Ae. aegypti is the primary local vector of these infections. PMID- 27376503 TI - Kato-Katz and Lumbreras rapid sedimentation test to evaluate helminth prevalence in the setting of a school-based deworming program. AB - The sensitivity of the Kato-Katz test is suboptimal for the evaluation of intestinal helminth prevalence. Moreover, during mass deworming, as helminth egg burden decreases, the sensitivity is likely to decrease. The Lumbreras rapid sedimentation (Lumbreras) is a low-cost non-quantitative test, but may provide useful information in low burden areas. We compared the prevalence of intestinal helminth infections assessed by the Kato-Katz and the Lumbreras rapid sedimentation test on 3 stool specimens from each of 1083 children. The sensitivities were compared using the McNemar paired test. Using the combined outcome of the 3 different stool tests as the standard, Kato-Katz had lower sensitivity than Lumbreras rapid sedimentation tests for Ascaris lumbricoides (85.1% vs. 95.1%, p = 0.03), Hymenolepis nana (77.7% vs. 97.9%, p < 0.01), Trichuris trichura (41.7% vs. 100%, p = 0.01), hookworm (0% vs. 100%, p = 0.01), and Strongyloides stercoralis (0% vs. 88%, p < 0.01). Kato-Katz demonstrated significantly lower sensitivity, missing most T. trichiura, hookworm, and S. stercoralis infections. The combination of Kato-Katz and Lumbreras rapid sedimentation tests enables the detection of more intestinal helminths infections in post-deworming low prevalence areas. PMID- 27376504 TI - Enhancing best practices in ophthalmology for prevention of nosocomial epidemic keratoconjunctivitis infections. AB - Epidemic keratoconjunctivitis (EKC) outbreaks were reported as early as the 1940s in the United States. Nearly 80 years later, EKC remains a major eye health concern in the US and worldwide. Of particular concern is that a significant number of EKC cluster outbreaks in the US are healthcare acquired infections (HAIs) at ophthalmology offices. Therefore, immediate attention to enhancing best practices of standardization and universal precautions in ophthalmology is paramount. PMID- 27376505 TI - Everolimus for neurological and psychiatric diseases: Friend or foe? PMID- 27376506 TI - Evidence of altered membrane phospholipid metabolism in the anterior cingulate cortex and striatum of patients with bipolar disorder I: A multi-voxel (1)H MRS study. AB - BACKGROUND: Previous proton magnetic resonance spectroscopy ((1)H MRS) studies have reported elevated glycerophosphocholine plus phosphocholine (GPC+PC) in the basal ganglia of patients with bipolar disorders (BD), which implicates an imbalance between synthesis and degradation activity of neuronal and glia membrane phospholipids (MPLs). However, the full extent of altered metabolites of MPLs in subareas within the basal ganglia, such as caudate and putamen, as well as anterior cingulate cortex (ACC) of BD patients is poorly understood. METHODS: Multi-voxel (1)H MRS measurements were acquired in 50 type-one BD (BD-I) and 44 healthy controls (HC) on a 3-T MRI scanner. Four different anatomically defined voxels covering ACC, caudate and putamen were systematically extracted and quantified using LCModel. Group differences in absolute GPC+PC and other metabolites were tested with age and gender as covariates. RESULTS: BD-I patients had higher GPC+PC levels in the anterior-dorsal ACC (p = 0.037), caudate (p = 0.005) and putamen (p = 0.004) compared to HC. GPC+PC levels in the caudate were elevated most significantly in currently unmediated BD-I patients (p = 0.022) and were positively correlated with HAM-D scores (r = 0.51, p = 0.005). PCr+Cr and myo-inositol levels were also significantly higher in the caudate head (F(1,45) = 6.010, p = 0.018) of patients compared to HC. NAA and glutamate levels were not significantly different between BD-I and HC in these regions (p > 0.05). CONCLUSION: The increased GPC+PC in BD-I patients may reflect an imbalance in the MPL metabolism. Caudate GPC+PC levels may be a potential biomarker for depressive symptoms in BD. PMID- 27376508 TI - Multi-locus sequence analysis for identification of Achromobacter xylosoxidans from blood culture. PMID- 27376510 TI - Fluorescence and visual detection of fluoride ions using a photoluminescent graphene oxide paper sensor. AB - The instant and on-site detection of trace aqueous fluoride ions is still a challenge for environmental monitoring and protection. This work demonstrates a new analytical method and its utility of a paper sensor for visual detection of F(-) on the basis of the fluorescence resonance energy transfer (FRET) between photoluminescent graphene oxide (GO) and silver nanoparticles (AgNPs) through the formation of cyclic esters between phenylborinic acid and diol. The fluorescence of GO was quenched by the AgNPs, and trace F(-) can recover the fluorescence of the quenched photoluminescent GO. The increase in fluorescence intensity is proportional to the concentration of F(-) in the range of 0.05-0.55 nM, along with a limit of detection (LOD) as low as 9.07 pM. Following the sensing mechanism, a paper-based sensor for the visual detection of aqueous F(-) has been successfully developed. The paper sensor showed high sensitivity for aqueous F( ), and the LOD could reach as low as 0.1 MUM as observed by the naked eye. The very simple and effective strategy reported here could be extended to the visual detection of a wide range of analytes in the environment by the construction of highly efficient FRET nanoprobes. PMID- 27376507 TI - Long-term live-cell imaging reveals new roles for Salmonella effector proteins SseG and SteA. AB - Salmonella Typhimurium is an intracellular bacterial pathogen that infects both epithelial cells and macrophages. Salmonella effector proteins, which are translocated into the host cell and manipulate host cell components, control the ability to replicate and/or survive in host cells. Due to the complexity and heterogeneity of Salmonella infections, there is growing recognition of the need for single-cell and live-cell imaging approaches to identify and characterize the diversity of cellular phenotypes and how they evolve over time. Here, we establish a pipeline for long-term (17 h) live-cell imaging of infected cells and subsequent image analysis methods. We apply this pipeline to track bacterial replication within the Salmonella-containing vacuole in epithelial cells, quantify vacuolar replication versus survival in macrophages and investigate the role of individual effector proteins in mediating these parameters. This approach revealed that dispersed bacteria can coalesce at later stages of infection, that the effector protein SseG influences the propensity for cytosolic hyper replication in epithelial cells, and that while SteA only has a subtle effect on vacuolar replication in epithelial cells, it has a profound impact on infection parameters in immunocompetent macrophages, suggesting differential roles for effector proteins in different infection models. PMID- 27376509 TI - Gene signatures of estrogen and progesterone receptor pathways predict the prognosis of colorectal cancer. AB - The associations of estrogen receptor (ER) and progesterone receptor (PR) pathways with the prognosis of colorectal cancer (CRC) are still controversial. The aim of this study was to readdress these issues by introducing a gene signature-based approach to semiquantitate pathway activity. In this approach, the ER and PR pathway activities in CRC were computed based on the expression profiles of the signature genes of ER and PR pathways, respectively. The results showed that the ER pathway activity was progressively significantly decreased from normal colorectal mucosa, colorectal adenoma to CRC. ER pathway signaling was a favorable factor for the presence of microsatellite stability (MSS) in CRC in seven cohorts tested, while was an unfavorable factor for cancer recurrence in all four CRC cohorts tested (n = 1122; overall HR: 0.311, 95% CI: 0.199-0.488, P < 0.001). Subset stratification in stage II patients showed that ER pathway remained significantly inversely associated with recurrence. PR pathway was also suppressed in colorectal tumors and inversely associated with recurrence of CRC, but to a much lesser extent than ER pathway. Moreover, the inverse association of PR pathway with cancer recurrence was more likely observed in CRC with high ER pathway activity, suggesting the interactions between the two pathways. PR pathway was not associated with MSS in CRC, but it was more significant than ER pathway associated with advance cancer stages and cancer response to adjuvant chemotherapy. These results suggested the potential application of the gene signatures of ER and PR pathways, especially the former, as novel markers for prognosis and management of CRC. PMID- 27376511 TI - Near-Zero Thermal Expansion and High Ultraviolet Transparency in a Borate Crystal of Zn4 B6 O13. AB - Intrinsic isotropic near-zero thermal expansion is discovered in borate crystal Zn4 B6 O13 with high transparency in the ultraviolet region. First-principles calculations demonstrate that the very low thermal expansion originates mainly from the invariability of the solid [B24 O48 ] truncated octahedra that are fixed by the [Zn4 O13 ] clusters in the ZBO structure. PMID- 27376512 TI - DNA methyltransferase inhibitors: an updated patent review (2012-2015). AB - INTRODUCTION: DNA methyltransferases (DNMTs), important enzymes involved in epigenetic regulation of gene expression, represent promising targets in cancer therapy. DNMT inhibitors (DNMTi), which can modulate the aberrant DNA methylation pattern in a reversible way via inhibiting DNMT activity, have attracted significant attention in recent years. AREAS COVERED: This review outlines the newly patented inhibitors targeting DNMTs, mainly incorporating small molecular inhibitors and oligonucleotide derivatives. The chemical structures, biological activity, and the encouraging clinical research in progress are delineated in detail. EXPERT OPINION: Two drugs, azacitidine and decitabine, have evidently shown efficacy in hematologic malignancies, yet do not work well on solid tumors, have low specificity, substantial toxicity, and poor bioavailability. With the rapid advancement in systems biology, drug combinations, such as DNMTi, in conjugation with histone deacetylase inhibitors (HDACi) or immunotherapy, probably serve as an efficient way of implementing epigenetic therapy. Meanwhile, the resolved autoinhibitory structures of DNMTs afford a novel strategy for targeting the protein-protein interface involved in the autoinhi-bitory interactions. The molecular mechanism underlying the conformational transitions would also shed new light on the design of allosteric inhibitors. Both strategies would produce inhibitors with more selectivity compared to nucleotide derivatives. PMID- 27376513 TI - An Unusual Storm Within the Gastroduodenal Tract. PMID- 27376514 TI - Stone-containing Cystic Mass at the Portal Hilus of the Liver in an Asymptomatic Young Female Patient. PMID- 27376515 TI - Reply. PMID- 27376516 TI - The Intensiveness of Intensive Enteral Nutrition Therapy. PMID- 27376518 TI - An Unusually Located Colonic Mass. PMID- 27376519 TI - Reply. PMID- 27376520 TI - An Unusual Case of Right Lower Abdominal Pain. PMID- 27376521 TI - He Did Not Cry Wolf: The Case of a Man With Lupus and 10 Years of Dysphagia. PMID- 27376522 TI - Abdominal Pain With an Unusual Radiographic Image. PMID- 27376523 TI - Reply. PMID- 27376524 TI - A Rare Cause of a Positive Fecal Occult Blood Test. PMID- 27376525 TI - Reply. PMID- 27376526 TI - Distressing Trespass. PMID- 27376527 TI - Statin Use in Patients With Hepatitis C-related Cirrhosis: True Benefit or Immortal Time Bias? PMID- 27376528 TI - Is Magnetic Resonance Imaging Really More Accurate for Classifying Steatosis Than Controlled Attenuation Parameter? PMID- 27376529 TI - Discordant inflammatory changes in the apophyseal and sacroiliac joints: serial observations in enthesitis-related arthritis. AB - OBJECTIVE: To determine the extent to which inflammation of the sacroiliac joints (SIJs) and apophyseal joints (AJs) changes concordantly after treatment in enthesitis-related arthritis (ERA). METHODS: A retrospective study was performed with institutional review board approval. 31 young patients with ERA who had been scanned between March 2009 and November 2014 were included. All patients had post contrast imaging of the SIJs and lumbar spine and short tau inversion-recovery (STIR) images of the SIJs. The severity of sacroiliitis was scored using a modification of an established technique, and inflammation of the AJs was evaluated using a recently described grading system. The changes in SIJ and AJ scores after treatment were classified as either concordant or discordant, and the proportion of scan pairs in these groups was recorded. In addition, the correlation between change in SIJ STIR score (Deltanfla) and change in AJ score (DeltaAJ) was assessed using Spearman's correlation coefficient. RESULTS: Of a total of 43 scan pairs, the changes in inflammation were concordant in 16 scan pairs and discordant in 27 scan pairs. There was no significant correlation between Deltanfla and DeltaAJ (R = 0.14, p = 0.37). CONCLUSION: Inflammatory changes in the SIJs and AJs are often discordant. This may be a reason why patients experience ongoing back pain despite apparent improvement in one or the other site. ADVANCES IN KNOWLEDGE: Inflammation may behave differently at different anatomical sites. The SIJs and AJs should both be imaged in patients with ERA with back pain. PMID- 27376530 TI - Potential Role of DARC-Chemokine Interaction in the Recruitment of Osteoclast Precursors in Response to Bacterial Lipopolysaccharide Challenge. AB - Duffy antigen receptor for chemokines (DARC) binds to a number of pro inflammatory chemokines, and since chemokines are known to regulate trafficking of osteoclast (OC) precursors, we predicted that DARC would regulate OC recruitment to sites of inflammation by modulating chemokine activity. To test this hypothesis, we evaluated the mRNA expression of Darc and the chemokines known to bind to DARC, in endothelial cells treated with bacterial lipopolysaccharide (LPS). The mRNA expression of Mcp-1, Rantes, Darc and Ccr5 was significantly increased in endothelial cells in response to LPS treatment. Blocking the function of DARC with neutralizing antibody partially abrogated the effect of LPS on the mRNA expression of Mcp-1 and Rantes. In vivo, mice with targeted disruption of Darc gene (Darc-KO) and control wild-type (WT) mice were used to assess the role of DARC in response to single LPS application on the top of parietal bones. Five hours post-LPS injection, local expression of Cd14 mRNA (a marker of inflammatory monocytes) was significantly increased in both lines of mice. However, the magnitude of increase was greater in WT mice compared with Darc-KO mice suggesting a role for DARC in mediating the recruitment of monocytes in response to LPS. Histological staining for tartrate-resistant acid phosphatase (TRAP) in calvaria sections taken from the injection sites revealed a significant reduction in TRAP-labeled surface per bone surface in response to LPS in Darc-KO mice compared with WT mice. Based on these findings, we concluded that DARC regulates recruitment of OC precursors at the inflammation site, probably through regulation of chemokines transcytosis across endothelial cell barrier. PMID- 27376531 TI - From contraction to gene expression: nanojunctions of the sarco/endoplasmic reticulum deliver site- and function-specific calcium signals. AB - Calcium signals determine, for example, smooth muscle contraction and changes in gene expression. How calcium signals select for these processes is enigmatic. We build on the "panjunctional sarcoplasmic reticulum" hypothesis, describing our view that different calcium pumps and release channels, with different kinetics and affinities for calcium, are strategically positioned within nanojunctions of the SR and help demarcate their respective cytoplasmic nanodomains. SERCA2b and RyR1 are preferentially targeted to the sarcoplasmic reticulum (SR) proximal to the plasma membrane (PM), i.e., to the superficial buffer barrier formed by PM-SR nanojunctions, and support vasodilation. In marked contrast, SERCA2a may be entirely restricted to the deep, perinuclear SR and may supply calcium to this sub-compartment in support of vasoconstriction. RyR3 is also preferentially targeted to the perinuclear SR, where its clusters associate with lysosome-SR nanojunctions. The distribution of RyR2 is more widespread and extends from this region to the wider cell. Therefore, perinuclear RyR3s most likely support the initiation of global calcium waves at L-SR junctions, which subsequently propagate by calcium-induced calcium release via RyR2 in order to elicit contraction. Data also suggest that unique SERCA and RyR are preferentially targeted to invaginations of the nuclear membrane. Site- and function-specific calcium signals may thus arise to modulate stimulus-response coupling and transcriptional cascades. PMID- 27376532 TI - Single-cell RNA-seq technology lends a hand into HSC ontogeny. PMID- 27376533 TI - Effects of improved fat meat products consumption on emergent cardiovascular disease markers of male volunteers at cardiovascular risk. AB - High meat-product consumption has been related to cardiovascular disease (CVD). However, previous results suggest the benefits of consuming improved fat meat products on lipoprotein-cholesterol and anthropometric measurements. Present study aims to assess the effect of consuming different Pate and Frankfurter formulations on emergent CVD biomarkers in male volunteers at increased CVD risk. Eighteen male volunteers with at least two CVD risk factors were enrolled in a sequentially controlled study where different pork-products were tested: reduced fat (RF), omega-3-enriched-RF (n-3RF), and normal-fat (NF). Pork-products were consumed during 4-week periods separated by 4-week washout. The cardiometabolic index (CI), oxidized low density lipoproteins (oxLDL), apolipoproteins (Apo) A1 and B, homocysteine (tHcys), arylesterase (AE), C-reactive Protein (CRP), tumor necrotic factor-alpha (TNFalpha), and lipoprotein (a) (Lp(a)) were tested and some other related ratios calculated. AE, oxLDL and Lp(a), AE/HDLc, LDLc/Apo B, and AE/oxLDL rate of change were differently affected (P<0.01) by pork-products consumption. RF increased (P < 0.05) AE, AE/HDLc and AE/oxLDL ratios and decreased TNFalpha, tHcys; n-3RF increased (P < 0.001) AE, AE/HDLc and AE/oxLDL ratios and decreased (P < 0.05) Lp(a); while NF increased (P<0.05) oxLDL and Lp(a) levels. In conclusion, RF and n-3RF products affected positively the level of some emergent CVD markers. The high regular consumption of NF-products should be limited as significantly increased Lp(a) and oxLDL values. The high variability in response observed for some markers suggests the need to perform more studies to identify targets for RF- and n-3RF-products. Graphical Abstract Emergent CVD markers. PMID- 27376534 TI - PrP aggregation can be seeded by pre-formed recombinant PrP amyloid fibrils without the replication of infectious prions. AB - Mammalian prions are unusual infectious agents, as they are thought to consist solely of aggregates of misfolded prion protein (PrP). Generation of synthetic prions, composed of recombinant PrP (recPrP) refolded into fibrils, has been utilised to address whether PrP aggregates are, indeed, infectious prions. In several reports, neurological disease similar to transmissible spongiform encephalopathy (TSE) has been described following inoculation and passage of various forms of fibrils in transgenic mice and hamsters. However, in studies described here, we show that inoculation of recPrP fibrils does not cause TSE disease, but, instead, seeds the formation of PrP amyloid plaques in PrP-P101L knock-in transgenic mice (101LL). Importantly, both WT-recPrP fibrils and 101L recPrP fibrils can seed plaque formation, indicating that the fibrillar conformation, and not the primary sequence of PrP in the inoculum, is important in initiating seeding. No replication of infectious prions or TSE disease was observed following both primary inoculation and subsequent subpassage. These data, therefore, argue against recPrP fibrils being infectious prions and, instead, indicate that these pre-formed seeds are acting to accelerate the formation of PrP amyloid plaques in 101LL Tg mice. In addition, these data reproduce a phenotype which was previously observed in 101LL mice following inoculation with brain extract containing in vivo-generated PrP amyloid fibrils, which has not been shown for other synthetic prion models. These data are reminiscent of the "prion-like" spread of aggregated forms of the beta-amyloid peptide (Abeta), alpha-synuclein and tau observed following inoculation of transgenic mice with pre-formed seeds of each misfolded protein. Hence, even when the protein is PrP, misfolding and aggregation do not reproduce the full clinicopathological phenotype of disease. The initiation and spread of protein aggregation in transgenic mouse lines following inoculation with pre-formed fibrils may, therefore, more closely resemble a seeded proteinopathy than an infectious TSE disease. PMID- 27376535 TI - Biology of lung cancer: genetic mutation, epithelial-mesenchymal transition, and cancer stem cells. AB - At present, most cases of unresectable cancer cannot be cured. Genetic mutations, EMT, and cancer stem cells are three major issues linked to poor prognosis in such cases, all connected by inter- and intra-tumor heterogeneity. Issues on inter-/intra-tumor heterogeneity of genetic mutation could be resolved with recent and future technologies of deep sequencers, whereas, regarding such issues as the "same genome, different epigenome/phenotype", we expect to solve many of these problems in the future through further research in stem cell biology. We herein review and discuss the three major issues in the biology of cancers, especially from the standpoint of stem cell biology. PMID- 27376536 TI - Interplay Between Expression of Sulfur Assimilation Pathway Genes and Zn(2+) and Pb(2+) Stress in Acidithiobacillus ferrooxidans. AB - We have previously demonstrated that in Acidithiobacillus ferrooxidans, resistance to the highly toxic divalent cation Cd(2+) is mediated in part by the sulfur assimilation pathway (SAP) and enhanced intracellular concentrations of cysteine and glutathione(GSH) (Zheng et al., Extremophiles 19:429-436, 2015). In this paper, we investigate the interplay between Zn(2+) and Pb(2+) resistances, SAP gene expression, and thiol-containing metabolite levels. Cells grown in the presence of 300 mM Zn(2+) had enhanced activities of the following enzymes: adenosylphosphosulphate reductase (APR, 40-fold), serine acetyltransferase (SAT, 180-fold), and O-acetylserine (thiol) lyase (OAS-TL, 230-fold). We investigated the concentrations of mRNA transcripts of the genes encoding these enzymes in cells grown in the presence of 600 mM Zn(2+): transcripts for 4 SAP genes ATPS(ATP sulphurylase), APR, SiR(sulfite reductase), SAT, and OAS-TL-each showed a more than three-fold increase in concentration. At the metabolite level, concentrations of intracellular cysteine and glutathione (GSH) were nearly doubled. When cells were grown in the presence of 10 mM Pb(2+), SAP gene transcript concentrations, cysteine, and GSH concentrations were all decreased, as were SAP enzyme activities. These results suggested that Zn(2+) induced SAP pathway gene transcription, while Pb(2+) inhibited SAP gene expression and enzyme activities compared to the pathway in most organisms. Because of the detoxification function of thiol pool, the results also suggested that the high resistance of A. ferrooxidans to Zn(2+) may also be due to regulation of GSH and the cysteine synthesis pathway. PMID- 27376538 TI - [Therapy of severe barbiturate intoxications]. PMID- 27376537 TI - In silico proposition to predict cluster of B- and T-cell epitopes for the usefulness of vaccine design from invasive, virulent and membrane associated proteins of C. jejuni. AB - PURPOSE: Campylobacter jejuni is the one of the leading causes of bacterial diarrheal illness worldwide. This study aims to design specific epitopes for the utility of designing peptide vaccine(s) against C. jejuni by targeting invasive, virulent and membrane associated proteins like FlaA, Cia, CadF, PEB1, PEB3 and MOMP. METHODS: In the present study, various immunoinformatics approaches have been applied to design a potential epitope based vaccine against C. jejuni. The tools include Bepipred, ABCpred, Immune Epitope databse (IEDB) resource portal, Autodock vina etc. RESULTS: Peptides "EINKN", "TGSRLN", "KSNPDI", "LDENGCE" respectively from FlaA, MOMP, PEB3, CadF proteins were found to be the most potential B cell epitopes while peptides "FRINTNVAA", "NYFEGNLDM", "YKYSPKLNF", "YQDAIGLLV", "FRNNIVAFV" and "LIMPVFHEL" respectively from Fla, CadF, MOMP, PEB1A, PEB3 and Cia might elicit cell mediated immunity and "IFYTTGSRL" from MOMP protein might elicit both humoral and cell-mediated immunity. All these potential peptidic epitopes showed almost 80-100 % conservancy in different strains of C jejuni with varying proportions of population coverage ranging from 22-60 %. Further authentication of these peptide epitopes as probable vaccine candidate was mediated by their binding to specific HLA alleles using in silico docking technique. CONCLUSION: Based on the present study, it could be concluded that these predicted epitopes might be used to design a vaccine against C. jejuni bacteria and thus, could be validated in model hosts to verify their efficacy as vaccine. PMID- 27376539 TI - [Decrease of surfactant release by phenobarbital intoxication is possible]. PMID- 27376540 TI - [Procalcitonin as a tool for the assessment of successful therapy of severe sepsis : An analysis using clinical routine data]. AB - INTRODUCTION: Procalcitonin (PCT) is a well-evaluated biomarker for the detection of severe bacterial infections and monitoring effectiveness of antibiotic therapy. This study aims to evaluate the usefulness of PCT in a clinical routine setting. MATERIALS AND METHODS: Of 358,763 clinical cases from 7 German hospitals in 2012 and 2013, 3854 cases had an ICD-10 code representing sepsis. A total of 1778 cases had pathologic PCT and one episode of infection. Of those, 671 showed a series of measures that was suitable to assess treatment success using PCT reduction. Propensity score matching was used to create two comparable groups with 211 patients in each group. RESULTS: The group with PCT reduction within 12 days showed a highly significant better proportion of survival (146/211 vs. 17/211; p < 0.0001). The odds ratio for death according to PCT reduction vs. nonreduction is 25.64 (p < 0.0001; 95 % CI: 14.49-45.45). PCT was normalized after an average of 6.2 days. DISCUSSION: The difference in survival implicates that PCT reduction is a suitable surrogate parameter to indicate successful antimicrobial therapy. Successful antibiotic therapy is a proven predictor for survival in sepsis. This study also showed concordant results in the group of patients with sepsis after abdominal surgery. Results from subgroup analyses confirm the initial findings. PCT reduction was used as surrogate for therapy success, as the antimicrobial therapy was not electronically available. CONCLUSION: PCT reduction is a strong predictor for survival. However, the data show that overall use of PCT to monitor sepsis therapy is not yet routinely established. Hospitals should establish algorithms for sepsis treatment that include PCT for the assessment of adequacy and the monitoring of success of the antimicrobial therapy. PMID- 27376541 TI - [Hospital emergency plan: the consequence-based model]. AB - A very basic aim of disaster planning is to reduce complexity. This is not only the case for emergency services outside of hospitals, but also for hospitals facing the pressure to manage any kind of disaster. Despite some disadvantages, hospital disaster planning is traditionally based on the distinction between internal and external scenarios. In this article, we describe for the first time a new model used to prepare a hospital emergency plan. We call it the consequence based model. It is based on the two major consequences that any possible scenario will have on a hospital: breakdown of functionality and overrun of capacity. The consequence-based model will automatically focus the planning on restoring functionality and increasing capacity. PMID- 27376542 TI - Using systems biology to evaluate targets and mechanism of action of drugs for diabetes comorbidities. AB - Medications approved for diabetes-associated renal and cardiovascular morbidities and candidate drugs currently in development are subject to substantial variability in drug response. Heterogeneity on a molecular phenotype level is not apparent at clinical presentation, which means that inter-individual differences in drug effect at the molecular level are masked. These findings identify the need for optimising patient phenotyping via use of molecular biomarkers for a personalised therapy approach. Molecular diversity may, on the one hand, result from the effect of genetic polymorphisms on drug transport, metabolism and effective target modulation. Equally relevant, differences may be due to molecular pathologies. The presence of distinct molecular phenotypes is suggested by classifiers aimed at modelling progressive disease. Such functions for prognosis incorporate a complex set of clinical variables or a multitude of molecular markers reflecting a diverse set of molecular disease mechanisms. This information on disease pathology and the mechanism of action of the drug needs to be systematically integrated with data on molecular biomarkers to develop an experimental tool for personalising medicine. The large amount of molecular data available for characterising diabetes-associated morbidities allows for elucidation of molecular process model representations of disease pathologies. Selecting biomarker candidates on such grounds and, in turn identifying their association with progressive disease allows for the identification of molecular processes associated with disease progression. The molecular effect of a drug can also be modelled at a molecular process level, and the integration of disease pathology and drug effect molecular models reveals candidate biomarkers for assessing drug response. Such tools serve as enrichment strategies aimed at adding precision to drug development and use. PMID- 27376543 TI - Metabolic flexibility and oxidative capacity independently associate with insulin sensitivity in individuals with newly diagnosed type 2 diabetes. AB - AIMS/HYPOTHESIS: Both inherited and acquired insulin resistance have been associated with abnormal muscle mitochondrial function. At whole-body level, maximal oxygen uptake ([Formula: see text]) and/or metabolic flexibility (as given by DeltaRQ) reflect certain features of mitochondrial function. This study tests the hypotheses (1) that [Formula: see text] and DeltaRQ correlate tightly with each other and with insulin sensitivity and (2) that glycaemia, lipidaemia or subclinical inflammation would explain such relationships. METHODS: Near normoglycaemic individuals with type 2 diabetes mellitus (n = 136) with a short known disease duration (<12 months) underwent cycling spiroergometry, indirect calorimetry and hyperinsulinaemic-euglycaemic clamp tests. RESULTS: Both [Formula: see text] (r = 0.39, p < 0.0001) and DeltaRQ (r = 0.32, p < 0.0001) correlated positively with whole-body insulin sensitivity, even after adjusting for anthropometric variables, glycaemia and glucose-lowering medication, but not after adjusting for NEFA. [Formula: see text] further correlated negatively with circulating high-sensitivity C-reactive protein concentration. However, [Formula: see text] did not relate to DeltaRQ, even after adjusting for whole-body insulin sensitivity. CONCLUSIONS/INTERPRETATION: Oxidative capacity and metabolic flexibility are independent determinants of insulin sensitivity but are influenced by circulating NEFA in recent-onset type 2 diabetes. ClinicalTrial.gov registration no: NCT01055093. PMID- 27376544 TI - Clinical evaluation of composite restorations in Er:YAG laser-prepared cavities re-wetting with chlorhexidine. AB - OBJECTIVES: The objective of this study was to evaluate longitudinally the composite restorations, performed in cavities prepared by Er:YAG or conventional bur, and dentin re-wetting with water or chlorhexidine. MATERIALS AND METHODS: Twenty individuals with four active caries with cavitation reaching the dentin located on the occlusal surface of molars counterparts are selected. The teeth of each individual were randomly assigned into four groups: (I) Er:YAG laser (260 mJ/4 Hz) re-wetting with chlorhexidine, (II) Er:YAG laser (260 mJ/4 Hz) re wetting with deionized water, (III) conventional method re-wetting with chlorhexidine, and (IV) conventional method re-wetting with deionized water. The teeth were isolated, prepared cavities, phosphoric acid etching, and re-wetting according to previously assigned method. Restoration was performed employing the Single Bond 2 and Z350XT resin. Clinical follow-up was held after the polishing of the restoration (baseline) and 6 and 12 months of the making of the restoration using the modified USPHS criteria. The restorations were qualitatively analyzed by means of photographs. In the evaluation period, replicas of the restorations were analyzed by SEM. Data were analyzed by statistics using chi-square test (p < 0.05). RESULTS: After 12 months of clinical evaluation, groups prepared with laser and re-wetting with chlorhexidine and water showed the lowest marginal staining value. There was no statistical difference between the groups for other factors. SEM analysis revealed that a non expressive amount of restorations showed gaps and irregularities of tooth restoration interface after 6 and 12 months compared to the baseline. CONCLUSION: The restorations performed in laser-prepared cavities, regardless of the re wetting, presented the best clinical performance over the evaluated period. CLINICAL RELEVANCE: Laser-prepared teeth, regardless of re-wetting, showed greater resistance to marginal discoloration. PMID- 27376545 TI - Umbilical cord blood transplantation for adults using tacrolimus with two-day very-short-term methotrexate for graft-versus-host disease prophylaxis. AB - Cord blood transplantation (CBT) is an alternative approach to allogeneic stem cell transplantation. However, CBT is associated with issues including pre engraftment immune reaction (PIR), engraftment syndrome (ES), and graft failure (GF). Tacrolimus (TAC) and short-term methotrexate (sMTX: days 1, 3, 6, and/or 11) are used for graft-versus-host disease (GVHD) prophylaxis during CBT; however, sMTX does not accelerate neutrophil engraftment. Therefore, we hypothesized that lower doses of sMTX [very-short-term MTX (vsMTX): 10 and 7mg/m(2) on days 1 and 3, respectively] with TAC reduce the risk of GF without increasing post-transplantation immune reactions during CBT. We retrospectively analyzed 40 patients who received TAC with vsMTX for GVHD prophylaxis. PIR and ES developed in 4 patients. The cumulative incidence of neutrophil engraft at day 60 was 92.5%. No cases of primary graft failure were noted. The cumulative incidence of grades II-III GVHD was 48.1% at day 100, and the cumulative 100-day incidence of nonrelapse mortality was 12.5%. This study suggests that TAC with vsMTX reduces the risk of PIR and ES during CBT and stimulates neutrophil engraftment, but may be associated with slightly higher aGVHD compared with calcineurin inhibitor and sMTX. Therefore, we recommend vsMTX plus TAC as an option for GVHD prophylaxis during CBT. PMID- 27376547 TI - Charge density waves in strongly correlated electron systems. AB - Strong electron correlations are at the heart of many physical phenomena of current interest to the condensed matter community. Here we present a survey of the mechanisms underlying such correlations in charge density wave (CDW) systems, including the current theoretical understanding and experimental evidence for CDW transitions. The focus is on emergent phenomena that result as CDWs interact with other charge or spin states, such as magnetism and superconductivity. In addition to reviewing the CDW mechanisms in 1D, 2D, and 3D systems, we pay particular attention to the prevalence of this state in two particular classes of compounds, the high temperature superconductors (cuprates) and the layered transition metal dichalcogenides. The possibilities for quantum criticality resulting from the competition between magnetic fluctuations and electronic instabilities (CDW, unconventional superconductivity) are also discussed. PMID- 27376546 TI - The prognostic significance of surface dipeptidylpeptidase IV (CD26) expression in B-cell chronic lymphocytic leukemia. AB - A number of factors related to B-cell chronic lymphocytic leukemia (B-CLL) patients' prognosis have been identified. However, still some factors better reflecting disease activity in individual cases are explored. The study aimed to evaluate prognostic significance of dipeptidylpeptidase IV/CD26 expression on B CLL cells and its relationship with other well established prognostic factors. The study included 94 patients with newly diagnosed B-CLL and involved analysis of clinical, laboratory, flow-cytometry and cytogenetic data. Detailed analysis showed that CD26 expression on B-CLL cells correlates with Rai's clinical stage of the disease at diagnosis (p=0.034), beta2-microglobulin concentration (p=0.012), lactic acid dehydrogenase activity (p=0.045) and absolute lymphocytes' count (p=0.027) in the blood. The multivariate analysis revealed that time to treatment (TTT) was significantly influenced by Rai clinical stage, LDH activity in blood and CD26 expression on B-CLL cell's. Moreover, in the multivariate analysis restricted to the group of patients with documented cytogenetic risk (n=36) CD26 expression, Rai clinical stage and cytogenetic profile remained their independent impact on TTT. The results of our study indicate that the CD26 expression should be incorporated in B-CLL patients risk assessment along with well known prognostic factors, since it seems to have a relationship with the tumor mass and influences TTT. PMID- 27376548 TI - Poly(L-lactide) crystallization topography directs MC3T3-E1 cells response. AB - Biomaterial surface topography significantly influences cellular form and function. Using poly(L-lactic acid) films with normal spherulites, banded spherulites, and amorphous surfaces as model substrates, we conducted a systematic assessment of the role for polymer crystallization induced surface morphologies on cell growth and contact guidance. Microscopy and image analysis showed that the MC3T3-E1 cells spread out in a random fashion on the amorphous substrate. At 24 h post-seeding, MC3T3-E1 cells on both types of spherulite surfaces were elongated and aligned along the spherulite radius direction. For the banded spherulite surface with radial stripes and coupling annular grooves, the cell orientation and cell nuclear localization were related to the grooves structure. With increasing time, this orientation preference was weaker. These results demonstrate that the patterning of polymer crystallization structure provide important signals for guiding cells to exhibit characteristic orientation and morphology especially in the early stages of regeneration. PMID- 27376550 TI - Persistence of Lactobacilli in Postmenopausal Women - A Double-Blind, Randomized, Pilot Study. AB - AIM: To investigate the ability of lactobacilli to persist in the genital area (vagina and labia) of women after the topical application of an ointment containing Lactobacillus gasseri LN40, L. fermentum LN99 and L. rhamnosus LN113. Secondary objectives were to study the presence of Escherichia coli and other contaminants, as well as subjective symptoms in the genital tract. METHODS: Eighteen healthy postmenopausal women were randomized to use either the study product or placebo for 10 days. Gynecological examinations, labial and vaginal samplings for bacterial cultivation were performed at baseline (visit 1), after treatment (visit 2), and at a 10-day follow-up (visit 3). LN strains were identified by specific cultivation methods. Subjective symptoms were evaluated by a self-administered questionnaire. RESULTS: The presence of LN99 was shown in 7 out of 8 women in the investigational group at visit 2 (p < 0.001 compared to placebo) and in 5 out of 8 at visit 3 (p < 0.05), whereas the presence of LN113 was shown in 2 out of 8 at visit 2 and in 1 out of 8 at visit 3. Subjective symptoms were significantly reduced (p < 0.01) at visits 2 and 3 for both products. CONCLUSION: Topical application of a probiotic ointment is feasible to achieve persistence of lactobacilli for at least 10 days. PMID- 27376549 TI - Affinity and dose of TCR engagement yield proportional enhancer and gene activity in CD4+ T cells. AB - Affinity and dose of T cell receptor (TCR) interaction with antigens govern the magnitude of CD4+ T cell responses, but questions remain regarding the quantitative translation of TCR engagement into downstream signals. We find that while the response of mouse CD4+ T cells to antigenic stimulation is bimodal, activated cells exhibit analog responses proportional to signal strength. Gene expression output reflects TCR signal strength, providing a signature of T cell activation. Expression changes rely on a pre-established enhancer landscape and quantitative acetylation at AP-1 binding sites. Finally, we show that graded expression of activation genes depends on ERK pathway activation, suggesting that an ERK-AP-1 axis plays an important role in translating TCR signal strength into proportional activation of enhancers and genes essential for T cell function. PMID- 27376551 TI - Authors' Reply. PMID- 27376552 TI - Distribution of high-level mupirocin resistance among clinical MRSA. AB - Mupirocin is a topical antibiotic for methicillin-resistant Staphylococcus aureus (MRSA) decolonization in hospital settings and nursing homes and is used as a highly effective antibiotic against MRSA. In this study, we aimed to evaluate the frequency of high-level mupirocin-resistant (HLMR) strains among the MRSA subtypes. A total of 188 clinical MRSA isolates were collected from 2011 to 2014, and their susceptibility to antimicrobial agents and vancomycin resistance was evaluated using disc diffusion method and micro-dilution method, respectively. Furthermore, the presence of mecA, SSCmec, mupA and mupB was assessed by PCR. All isolates were multi-drug resistant (MDR) but 2 strains (1.06%) were resistant to mupirocin. Minimum inhibitory concentration (MIC) of vancomycin for 8 strains (4.7%) was higher than 2 MUg/ml. Of 188 isolates, 188 (100%), 64 (34.04%), 8 (4.3%), 150 (79.8%), 26 (13.8%), 2 (1.06) and 2 (1.06%) isolates possessed mecA, SCCmec types I, II, III, IV, mupA and mupB genes, respectively. Our data showed that despite infection control policy enforced by health care committee, the rate of mupirocin resistance among MRSA strains is continuously rising. PMID- 27376553 TI - Rapid and simple determination of T1 relaxation times in time-domain NMR by Continuous Wave Free Precession sequence. AB - Longitudinal (T1) and transverse (T2) relaxation times have been widely used in time-domain NMR (TD-NMR) to determine several physicochemical properties of petroleum, polymers, and food products. The measurement of T2 through the CPMG pulse sequence has been used in most of these applications because it denotes a rapid, robust method. On the other hand, T1 has been occasionally used in TD-NMR due to the long measurement time required to collect multiple points along the T1 relaxation curve. Recently, several rapid methods to measure T1 have been proposed. Those methods based upon single shot, known as Continuous Wave Free Precession (CWFP) pulse sequences, have been employed in the simultaneous measurement of T1 and T2 in a rapid fashion. However, these sequences can be used exclusively in instrument featuring short dead time because the magnitude of the signal at thermal equilibrium is required. In this paper, we demonstrate that a special CWFP sequence with a low flip angle can be a simple and rapid method to measure T1 regardless of instruments dead time. Experimental results confirmed that the method called CWFP-T1 may be used to measure both single T1 value and T1 distribution in heterogeneous samples. Therefore, CWFP-T1 sequence can be a feasible alternative to CPMG in the determination of physicochemical properties, particularly in processes where fast protocols are requested such as industrial applications. PMID- 27376554 TI - Effect of biophysical cues on reprogramming to cardiomyocytes. AB - Reprogramming of fibroblasts to cardiomyocytes offers exciting potential in cell therapy and regenerative medicine, but has low efficiency. We hypothesize that physical cues may positively affect the reprogramming process, and studied the effects of periodic mechanical stretch, substrate stiffness and microgrooved substrate on reprogramming yield. Subjecting reprogramming fibroblasts to periodic mechanical stretch and different substrate stiffness did not improve reprogramming yield. On the other hand, culturing the cells on microgrooved substrate enhanced the expression of cardiomyocyte genes by day 2 and improved the yield of partially reprogrammed cells at day 10. By combining microgrooved substrate with an existing optimized culture protocol, yield of reprogrammed cardiomyocytes with striated cardiac troponin T staining and spontaneous contractile activity was increased. We identified the regulation of Mkl1 activity as a new mechanism by which microgroove can affect reprogramming. Biochemical approach could only partially recapitulate the effect of microgroove. Microgroove demonstrated an additional effect of enhancing organization of sarcomeric structure, which could not be recapitulated by biochemical approach. This study provides insights into new mechanisms by which topographical cues can affect cellular reprogramming. PMID- 27376555 TI - Cyclopamine disrupts tumor extracellular matrix and improves the distribution and efficacy of nanotherapeutics in pancreatic cancer. AB - The dense extracellular matrix in pancreatic ductal adenocarcinoma dramatically reduces the penetration and efficacy of nanotherapeutics. Disruption of the tumor extracellular matrix may help improve the distribution and efficacy of nanotherapeutics in pancreatic cancer. In this study, we tested whether cyclopamine, a special inhibitor of the hedgehog signaling pathway with powerful anti-fibrotic activity, could promote the penetration and efficacy of nanotherapeutics in pancreatic cancer. It was shown that cyclopamine disrupted tumor extracellular fibronectins, decompressed tumor blood vessels, and improved tumor perfusion. Furthermore, cyclopamine improved the accumulation and intratumoral distribution of i.v.-administered fluorescence indicator-labeled nanoparticles. Finally, cyclopamine also significantly improved the tumor growth inhibition effect of i.v.-injected nanotherapeutics in pancreatic tumor xenograft mouse models. Thus, cyclopamine may have great potential to improve the therapeutic effects of nanomedicine in patients with pancreatic cancer. PMID- 27376556 TI - Approximating bone ECM: Crosslinking directs individual and coupled osteoblast/osteoclast behavior. AB - Osteoblast and osteoclast communication (i.e. osteocoupling) is an intricate process, in which the biophysical profile of bone ECM is an aggregate product of their activities. While the effect of microenvironmental cues on osteoblast and osteoclast maturation has been resolved into individual variables (e.g. stiffness or topography), a single cue can be limited with regards to reflecting the full biophysical scope of natural bone ECM. Additionally, the natural modulation of bone ECM, which involves collagenous fibril and elastin crosslinking via lysyl oxidase, has yet to be reflected in current synthetic platforms. Here, we move beyond traditional substrates and use cell-derived ECM to examine individual and coupled osteoblast and osteoclast behavior on a physiological platform. Specifically, preosteoblast-derived ECM is crosslinked with genipin, a biocompatible crosslinker, to emulate physiological lysyl oxidase-mediated ECM crosslinking. We demonstrate that different concentrations of genipin yield changes to ECM density, stiffness, and roughness while retaining biocompatibility. By approximating various bone ECM profiles, we examine how individual and coupled osteoblast and osteoclast behavior are affected. Ultimately, we demonstrate an increase in osteoblast and osteoclast differentiation on compact and loose ECM, respectively, and identify ECM crosslinking density as an underlying force in osteocoupling behavior. PMID- 27376557 TI - An implantable and controlled drug-release silk fibroin nanofibrous matrix to advance the treatment of solid tumour cancers. AB - The development of more effective cancer therapeutic strategies are still critically required. The maximization of the therapeutic effect in combination with avoiding the severe side effects on normal tissues when using chemotherapy drugs is still an urgent problem that requires improvements urgently. Here we provide implantable and controllable drug-release that utilises silk fibroin (SF) as a nanofibrous drug delivery system (DDS) for cancer treatment. A nanofibrous structure with controllable fibre diameter (<100 nm) was produced. The drug release rate of the SF DDS was controlled by applying a post-treatment process. In vitro anti-cancer (HCT116) results indicated that curcumin (CM)-SF nanofibrous matrix had a superior anti-cancer potential when the concentration was >5 MUg/mL. The mechanism could be explained by the cell cycle being held in the S phase. The toxic effect on normal cells (NCM460) was minimized by using a treatment concentration range (5-20 MUg/mL). Implantation of this DDS into the tumour site inhibited the growth of solid tumour; this offers an alternative approach for novel cancer therapy. PMID- 27376558 TI - Nanoparticle-facilitated autophagy inhibition promotes the efficacy of chemotherapeutics against breast cancer stem cells. AB - Cancer stem cells (CSCs) have garnered increasing attention over the past decade, as they are believed to play a crucial role in tumor initiation, progression and metastasis, relapse and drug resistance. Therapeutic strategies which simultaneously exterminate both bulk tumor cells and the rare CSC subpopulation may produce striking response and result in long-term tumor remission. Accumulating evidence provides insight into the function of autophagy in maintenance, plasticity and survival of CSCs. The role of autophagy in the susceptibility of breast CSCs to chemotherapeutics was investigated in the present work, reduced 'stemness' and increased susceptibility to chemotherapy drugs (doxorubicin, DOX and docetaxel, DTXL) were observed after chloroquine (CQ) mediated autophagy inhibition in sorted ALDH(hi) cells of breast cancer cell line MDA-MB-231. We further proved that nanoparticle-mediated autophagy inhibition promoted the efficacy of chemotherapeutics against ALDH(hi) MDA-MB-231 cells in vitro. Administration of drug delivery systems significantly prolonged the circulation half-life and augmented enrichment of two different drugs in tumor tissues and ALDH(hi) cells. More importantly, compared with single treatment, the combined delivery systems NPCQ/NPDOX and NPCQ/DOX (NPCQ/NPDTXL and NPCQ/DTXL) showed most effective and persistent tumor growth inhibitory effect by eliminating bulk tumor cells as well as CSCs (p < 0.01) in an MDA-MB-231 orthotopic tumor murine model. Therefore, our research provides new insights into the nanoparticle-facilitated combination of autophagy inhibition and chemotherapy for effective therapy of breast cancer. PMID- 27376559 TI - Fullerene/photosensitizer nanovesicles as highly efficient and clearable phototheranostics with enhanced tumor accumulation for cancer therapy. AB - A novel phototheranostic platform based on tri-malonate derivative of fullerene C70 (TFC70)/photosensitizer (Chlorin e6, Ce6) nanovesicles (FCNVs) has been developed for effective tumor imaging and treatment. The FCNVs were prepared from amphiphilic TFC70-oligo ethylene glycol -Ce6 molecules. The developed FCNVs possessed the following advantages: (i) high loading efficiency of Ce6 (up to ~57 wt%); (ii) efficient absorption in near-infrared light region; (iii) enhanced cellular uptake efficiency of Ce6 in vitro and in vivo; (iv) good biocompatibility and total clearance out from the body. These unique properties suggest that the as-prepared FCNVs could be applied as an ideal theranostic agent for simultaneous imaging and photodynamic therapy of tumor. This finding may provide a good solution to highly efficient phototheranostic applications based on fullerene derivatives fabricated nanostructures. PMID- 27376560 TI - 808 nm-excited upconversion nanoprobes with low heating effect for targeted magnetic resonance imaging and high-efficacy photodynamic therapy in HER2 overexpressed breast cancer. AB - To avoid the overheating effect of excitation light and improve the efficacy of photodynamic therapy (PDT) of upconversion nanoplatform, a novel nanoprobe based on 808 nm-excited upconversion nanocomposites (T-UCNPs@Ce6@mSiO2) with low heating effect and deep penetration has been successfully constructed for targeted upconversion luminescence, magnetic resonance imaging (MRI) and high efficacy PDT in HER2-overexpressed breast cancer. In this nanocomposite, photosensitizers (Ce6) were covalently conjugated inside of mesoporous silica to enhance the PDT efficacy by shortening the distance of fluorescence resonance energy transfer and to decrease the cytotoxicity by preventing the undesired leakage of Ce6. Compared with UCNPs@mSiO2@Ce6, UCNPs@Ce6@mSiO2 greatly promoted the singlet oxygen generation and amplified the PDT efficacy under the excitation of 808 nm laser. Importantly, the designed nanoprobe can greatly improve the uptake of HER2-positive cells and tumors by modifying the site-specific peptide, and the in vivo experiments showed excellent MRI and PDT via intravenous injection by modeling MDA-MB-435 tumor-bearing nude mice. Our strategy may provide an effective solution for overcoming the heating effect and improving the PDT efficacy of upconversion nanoprobes, and has potential application in visualized theranostics of HER2-overexpressed breast cancer. PMID- 27376561 TI - Mechanisms by which acellular biologic scaffolds promote functional skeletal muscle restoration. AB - Acellular biologic scaffolds derived from extracellular matrix have been investigated in preclinical and clinical studies as a regenerative medicine approach for volumetric muscle loss treatment. The present manuscript provides a review of previous studies supporting the use of extracellular matrix derived biologic scaffolds for the promotion of functional skeletal muscle tissue formation that is contractile and innervated. The manuscript also identifies key mechanisms that have been associated with ECM-mediated skeletal muscle repair, and provides hypotheses as to why there have been variable outcomes, ranging from successful to unsatisfactory, associated with ECM bioscaffold implantation in the skeletal muscle injury microenvironment. PMID- 27376562 TI - Integration of antimicrobial peptides with gold nanoparticles as unique non-viral vectors for gene delivery to mesenchymal stem cells with antibacterial activity. AB - Gold nanoparticles (AuNPs) have emerged as attractive non-viral gene vectors. However their application in regenerative medicine is still limited partially due to a lack of an intrinsic capacity to transfect difficult-to-transfect cells such as primary cells or stem cells. In current study, we report the synthesis of antimicrobial peptide conjugated cationic AuNPs (AuNPs@PEP) as highly efficient carriers for gene delivery to stem cells with antibacterial ability. The AuNPs@PEP integrate the advantages of cationic AuNPs and antibacterial peptides: the presence of cationic AuNPs can effectively condense DNA and the antimicrobial peptides are essential for the cellular & nucleus entry enhancement to achieve high transfection efficiency and antibacterial ability. As a result, antimicrobial peptides conjugated AuNPs significantly promoted the gene transfection efficiency in rat mesenchymal stem cells than pristine AuNPs, with a similar extent to those expressed by TAT (a well-known cell-penetrating peptide) modified AuNPs. More interestingly, the combinational system has better antibacterial ability than free antimicrobial peptides in vitro and in vivo, possibly due to the high density of peptides on the surface of AuNPs. Finally we present the concept-proving results that AuPs@PEP can be used as a carrier for in vivo gene activation in tissue regeneration, suggesting its potential as a multifunctional system with both gene delivery and antibacterial abilities in clinic. PMID- 27376563 TI - Three times greater weight of daytime than of night-time temperature on leaf unfolding phenology in temperate trees. AB - The phenology of spring leaf unfolding plays a key role in the structure and functioning of ecosystems. The classical concept of heat requirement (growing degree days) for leaf unfolding was developed hundreds of years ago, but this model does not include the recently reported greater importance of daytime than night-time temperature. A manipulative experiment on daytime vs night-time warming with saplings of three species of temperate deciduous trees was conducted and a Bayesian method was applied to explore the different effects of daytime and night-time temperatures on spring phenology. We found that both daytime and night time warming significantly advanced leaf unfolding, but the sensitivities to increased daytime and night-time temperatures differed significantly. Trees were most sensitive to daytime warming (7.4 +/- 0.9, 4.8 +/- 0.3 and 4.8 +/- 0.2 d advancement per degree Celsius warming (d degrees C-1 ) for birch, oak and beech, respectively) and least sensitive to night-time warming (5.5 +/- 0.9, 3.3 +/- 0.3 and 2.1 +/- 0.9 d degrees C-1 ). Interestingly, a Bayesian analysis found that the impact of daytime temperature on leaf unfolding was approximately three times higher than that of night-time temperatures. Night-time global temperature is increasing faster than daytime temperature, so model projections of future spring phenology should incorporate the effects of these different temperatures. PMID- 27376564 TI - Treatment of extensive erythema multiforme with topical gentian violet. AB - Topical and systemic therapies for erythema multiforme have been widely described in the literature. The pathogenesis of erythema multiforme involves increased expression of vascular endothelial growth factor resulting in the promotion of microvascular permeability and angiogenesis. Gentian violet has been shown to have antiangiogenic properties. Here, we present a case of erythema multiforme successfully treated with topical gentian violet. We report the case of a patient who presented with erythema multiforme. Prior pertinent history included diabetes mellitus type I, limiting the clinical use of systemic corticosteroids. Topical gentian violet was used to treat the cutaneous lesions. Our patient responded well to treatment with topical gentian violet with stabilization and resolution of the lesions without using systemic therapy that may pose serious side effects in the setting of other comorbidities such as diabetes mellitus type I. This case highlights the variable therapeutic options available for treatment of erythema multiforme, including topical gentian violet. While further studies are needed, this case demonstrates the antiangiogenic properties and clinical utility of topical gentian violet in the treatment of erythema multiforme. PMID- 27376565 TI - Clinical and morphological presentations of acute coronary syndrome without coronary plaque rupture - An intravascular ultrasound study. AB - BACKGROUND: Although acute coronary syndrome (ACS) mainly arises from plaque ruptures (PR), precise mechanisms underlying ACS without PR are unknown. We sought to examine clinical, angiographic and intravascular ultrasound (IVUS) characteristics of ACS without PR. METHODS AND RESULTS: Culprit lesions of 161 ACS patients were categorized by the presence or absence of PR (PR group: n=57, Non-PR group: n=104). Lower abdominal circumference (86+/-10cm vs 90+/-9cm, p=0.02), lower prevalence of myocardial infarction (53% vs 82%, p=0.0002), and higher prevalence of definite vasospasm (15% vs 2%, p=0.006) were found in Non-PR group. Morphologically, Non-PR group was associated with simpler Ambrose classification (36% vs 14%, p=0.004), less hypoechoic plaque (45% vs 65%, p=0.04) and lower incidence of IVUS-detected thrombus (21% vs 54%, p<0.0001), compared with PR group. On quantitative IVUS, although minimum lumen area (MLA) was similar between the groups, vessel (14.2+/-5.4mm(2) vs 17.5+/-5.1mm(2), p=0.0002) and plaque (11.6+/-5.0mm(2) vs 14.9+/-4.9mm(2), p<0.0001) areas were significantly smaller at MLA site in Non-PR group than in PR group. On multivariate analysis, average plaque area was only an independent IVUS-predictor of non-rupture ACS (odds ratio: 0.85, p=0.01). CONCLUSION: Compared to ACS with PR, non-rupture ACS arise from more hyperechoic (allegedly "stable") plaque with smaller vessel and plaque area, leading to lower incidence of thrombotic occlusion. Coronary vasospasm might be a possible pathogenic mechanism underlying non-rupture ACS. PMID- 27376566 TI - Evaluation of the characterization of thrombi in vitro by optical coherence tomography. AB - AIM: The purpose of this study was to provide a new assessable method of the optical coherence tomography (OCT) in characterization of thrombi with different concentrations of red blood cell (RBC). METHODS AND RESULTS: A series of thrombus models were constructed by using human blood in vitro. The thrombi were made by using human blood with different concentration of RBC (from 1% to 35%). Then tip of an FD-OCT catheter was put on the top of the thrombus to scan. After OCT being performed, all the acquired images were processed by a newly developed software to analyze the RBC levels related thrombus characteristics including attenuation, backscattering and light penetration depth. The attenuation was correlated with RBC concentration up to 9%. However, no apparent change was observed in thrombus with RBC concentration range from 10% to 35%. The same trend was seen in backscattering and penetration depth. CONCLUSIONS: FD-OCT is able to detect thrombus with different RBC concentrations up to 9%. PMID- 27376568 TI - In-stent accordion phenomenon. PMID- 27376567 TI - Stroke symptoms and risk for incident coronary heart disease in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. AB - BACKGROUND: Many adults without cerebrovascular disease report a history of stroke symptoms, which is associated with higher risk for stroke. Because stroke and coronary heart disease (CHD) share many risk factors, we examined the association between a history of stroke symptoms and incident CHD. METHODS: We analyzed data from 8999 black and 12,499 white REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants without a prior myocardial infarction, stroke or transitory ischemic attack enrolled in 2003-2007 (total participants=21,498, all >=45years of age). A history of stroke symptoms (i.e., unilateral weakness, unilateral numbness, full-field vision loss, half-field vision loss, understanding problems and communication problems) was assessed at baseline using the Questionnaire for Verifying Stroke-Free Status. Participants were followed for incident CHD and CHD death through December 2011. RESULTS: Overall, 3432 (16.0%) participants reported a history of stroke symptoms (1771 [19.7%] blacks and 1661 [13.3%] whites). There were 701 incident CHD events including 209 CHD deaths over a median follow-up of 5.8years. After adjustment for CHD risk factors, hazard ratios (95% confidence interval [95% CI]) for incident CHD associated with reporting any versus no stroke symptoms were 1.26 (1.04-1.51) in the overall population, 1.28 (0.99-1.65) among blacks and 1.23 (0.94-1.61) among whites. Multivariable-adjusted hazard ratios (95% CI) for CHD death associated with any versus no stroke symptoms were 1.50 (1.10-2.06) overall, 1.58 (1.07-2.32) among blacks and 1.41 (0.82-2.43) among whites. CONCLUSION: A history of stroke symptoms is associated with a higher incidence of CHD among black and white adults. PMID- 27376569 TI - Ventricular tachyarrhythmia during pregnancy in women with heart disease: Data from the ROPAC, a registry from the European Society of Cardiology. AB - OBJECTIVES: To describe the incidence, onset, predictors and outcome of ventricular tachyarrhythmia (VTA) in pregnant women with heart disease. BACKGROUND: VTA during pregnancy will cause maternal morbidity and even mortality and will have impact on fetal outcome. Insufficient data exist on the incidence and outcome of VTA in pregnancy. METHODS AND RESULTS: From January 2007 up to October 2013, 99 hospitals in 39 countries enrolled 2966 pregnancies in women with structural heart disease. Forty-two women (1.4%) developed clinically relevant VTA during pregnancy, which occurred mainly in the third trimester (48%). NYHA class >1 before pregnancy was an independent predictor for VTA. Heart failure during pregnancy was more common in women with VTA than in women without VTA (24% vs. 12%, p=0.03) and maternal mortality was respectively 2.4% and 0.3% (p=0.15). More women with VTA delivered by Cesarean section than women without VTA (68% vs. 47%, p=0.01). Neonatal death, preterm birth (<37weeks), low birthweight (<2500g) and Apgar score <7 occurred more often in women with VTA (4.8% vs. 0.3%, p=0.01; 36% vs. 16%, p=0.001; 33% vs. 15%, p=0.001 and 25% vs. 7.3%, p=0.001, respectively). CONCLUSIONS: VTA occurred in 1.4% of pregnant women with cardiovascular disease, mainly in the third trimester, and was associated with heart failure during pregnancy. NYHA class before pregnancy was predictive. VTA during pregnancy had clear impact on fetal outcome. PMID- 27376571 TI - Electric Field Induce Blue Shift and Intensity Enhancement in 2D Exciplex Organic Light Emitting Diodes; Controlling Electron-Hole Separation. AB - A simple but novel method is designed to study the characteristics of the exciplex state pinned at a donor-acceptor abrupt interface and the effect an external electric field has on these excited states. The reverse Onsager process, where the field induces blue-shifted emission and increases the efficiency of the exciplex emission as the e-h separation reduces, is discussed. PMID- 27376570 TI - Metformin and contrast-induced acute kidney injury in diabetic patients treated with primary percutaneous coronary intervention for ST segment elevation myocardial infarction: Amulticenter study. AB - AIM: To analyze the association between chronic metformin treatment and the development of contrast-induced acute kidney injury (CI-AKI) after primary percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI). METHODS: Patients with type 2 diabetes mellitus (T2DM) treated with PCI <24h in 2 coronary care units were included. Serum creatinine (Cr) was measured before and <48h after PCI. CI-AKI was defined as an increase in Cr>27MUmol/l (0.3mg/dl) or >50% over baseline after PCI. Since PCI was urgent, metformin could not be withheld prior to PCI but was usually stopped after PCI. RESULTS: Among the 372 patients included, 147 (40%) were using metformin, which had older diabetes, but had risk factors similar to patients without metformin. Baseline eGFR was better in patients under metformin therapy. After PCI, we observed an increase of ~10% in Cr, for both groups. There was a trend toward a lower rate of CI-AKI in patients under metformin (16% vs 25%, p=0.051). In patients with chronic kidney disease, 31 (26%) were under metformin therapy, and the rate of CI-AKI was similar in both groups (41% vs 40%, p=0.915). By multivariate analysis, metformin showed a trend toward a reduced rate of CI-AKI, even when adjusted for confounding (OR (95% CI): 0.548 (0.276-1.087)). No case of lactic acidosis was reported during the hospital stay. Moreover, there was no increased rate of cardiogenic shock or death with metformin treatment. CONCLUSION: In this multicenter observational study, chronic metformin treatment prior to primary PCI had no significant impact on CI-AKI. PMID- 27376572 TI - How fast is optically induced electron transfer in organic mixed valence systems? AB - The rate of thermally induced electron transfer in organic mixed valence compounds has thoroughly been investigated by e.g. temperature dependent ESR spectroscopy. However, almost nothing is known about the dynamics of optically induced electron transfer processes in such systems. Therefore, we investigated these processes in mixed valence compounds based on triphenylamine redox centres bridged by conjugated spacers by NIR transient absorption spectroscopy with fs time resolution. These experiments revealed an internal conversion (IC) process to be on the order of 50-200 fs which is equivalent to the back electron transfer after optical excitation into the intervalence charge transfer band. This IC is followed by ultrafast cooling to the ground state within 1 ps. Thus, in the systems investigated optically induced electron transfer is about 3-4 orders of magnitude faster than thermally induced ET. PMID- 27376573 TI - Novel and scalable solid-state synthesis of a nanocrystalline FeF3/C composite and its excellent electrochemical performance. AB - A scalable solid-state reaction is presented to synthesize an FeF3 cathode material by using PTFE as a source of both fluorine and carbon. The method yields nanocrystalline FeF3/C showing excellent electrochemical performance even without any conducting additive. This method can be utilized for engineering MFs' properties and developing other fluorine compounds. PMID- 27376574 TI - Inter-individual variability and genetic influences on cytokine responses to bacteria and fungi. AB - Little is known about the inter-individual variation of cytokine responses to different pathogens in healthy individuals. To systematically describe cytokine responses elicited by distinct pathogens and to determine the effect of genetic variation on cytokine production, we profiled cytokines produced by peripheral blood mononuclear cells from 197 individuals of European origin from the 200 Functional Genomics (200FG) cohort in the Human Functional Genomics Project (http://www.humanfunctionalgenomics.org), obtained over three different years. We compared bacteria- and fungi-induced cytokine profiles and found that most cytokine responses were organized around a physiological response to specific pathogens, rather than around a particular immune pathway or cytokine. We then correlated genome-wide single-nucleotide polymorphism (SNP) genotypes with cytokine abundance and identified six cytokine quantitative trait loci (QTLs). Among them, a cytokine QTL at the NAA35-GOLM1 locus markedly modulated interleukin (IL)-6 production in response to multiple pathogens and was associated with susceptibility to candidemia. Furthermore, the cytokine QTLs that we identified were enriched among SNPs previously associated with infectious diseases and heart diseases. These data reveal and begin to explain the variability in cytokine production by human immune cells in response to pathogens. PMID- 27376575 TI - Targeting beta1-integrin signaling enhances regeneration in aged and dystrophic muscle in mice. AB - Interactions between stem cells and their microenvironment, or niche, are essential for stem cell maintenance and function. Our knowledge of the niche for the skeletal muscle stem cell, i.e., the satellite cell (SC), is incomplete. Here we show that beta1-integrin is an essential niche molecule that maintains SC homeostasis, and sustains the expansion and self-renewal of this stem cell pool during regeneration. We further show that beta1-integrin cooperates with fibroblast growth factor 2 (Fgf2), a potent growth factor for SCs, to synergistically activate their common downstream effectors, the mitogen-activated protein (MAP) kinase Erk and protein kinase B (Akt). Notably, SCs in aged mice show altered beta1-integrin activity and insensitivity to Fgf2. Augmenting beta1 integrin activity with a monoclonal antibody restores Fgf2 sensitivity and improves regeneration after experimentally induced muscle injury. The same treatment also enhances regeneration and function of dystrophic muscles in mdx mice, a model for Duchenne muscular dystrophy. Therefore, beta1-integrin senses the SC niche to maintain responsiveness to Fgf2, and this integrin represents a potential therapeutic target for pathological conditions of the muscle in which the stem cell niche is compromised. PMID- 27376576 TI - Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. AB - Single-agent immunotherapy has achieved limited clinical benefit to date in patients with pancreatic ductal adenocarcinoma (PDAC). This may be a result of the presence of a uniquely immunosuppressive tumor microenvironment (TME). Critical obstacles to immunotherapy in PDAC tumors include a high number of tumor associated immunosuppressive cells and a uniquely desmoplastic stroma that functions as a barrier to T cell infiltration. We identified hyperactivated focal adhesion kinase (FAK) activity in neoplastic PDAC cells as an important regulator of the fibrotic and immunosuppressive TME. We found that FAK activity was elevated in human PDAC tissues and correlated with high levels of fibrosis and poor CD8(+) cytotoxic T cell infiltration. Single-agent FAK inhibition using the selective FAK inhibitor VS-4718 substantially limited tumor progression, resulting in a doubling of survival in the p48-Cre;LSL-Kras(G12D);Trp53(flox/+) (KPC) mouse model of human PDAC. This delay in tumor progression was associated with markedly reduced tumor fibrosis and decreased numbers of tumor-infiltrating immunosuppressive cells. We also found that FAK inhibition rendered the previously unresponsive KPC mouse model responsive to T cell immunotherapy and PD 1 antagonists. These data suggest that FAK inhibition increases immune surveillance by overcoming the fibrotic and immunosuppressive PDAC TME and renders tumors responsive to immunotherapy. PMID- 27376577 TI - Activation of the reward system boosts innate and adaptive immunity. AB - Positive expectations contribute to the clinical benefits of the placebo effect. Such positive expectations are mediated by the brain's reward system; however, it remains unknown whether and how reward system activation affects the body's physiology and, specifically, immunity. Here we show that activation of the ventral tegmental area (VTA), a key component of the reward system, strengthens immunological host defense. We used 'designer receptors exclusively activated by designer drugs' (DREADDs) to directly activate dopaminergic neurons in the mouse VTA and characterized the subsequent immune response after exposure to bacteria (Escherichia coli), using time-of-flight mass cytometry (CyTOF) and functional assays. We found an increase in innate and adaptive immune responses that were manifested by enhanced antibacterial activity of monocytes and macrophages, reduced in vivo bacterial load and a heightened T cell response in the mouse model of delayed-type hypersensitivity. By chemically ablating the sympathetic nervous system (SNS), we showed that the reward system's effects on immunity are, at least partly, mediated by the SNS. Thus, our findings establish a causal relationship between the activity of the VTA and the immune response to bacterial infection. PMID- 27376580 TI - The Cost of Residency Training in Teaching Health Centers. PMID- 27376578 TI - p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity. AB - In a search for mediators of the p53 tumor suppressor pathway, which induces pleiotropic and often antagonistic cellular responses, we identified the long noncoding RNA (lncRNA) NEAT1. NEAT1 is an essential architectural component of paraspeckle nuclear bodies, whose pathophysiological relevance remains unclear. Activation of p53, pharmacologically or by oncogene-induced replication stress, stimulated the formation of paraspeckles in mouse and human cells. Silencing Neat1 expression in mice, which prevents paraspeckle formation, sensitized preneoplastic cells to DNA-damage-induced cell death and impaired skin tumorigenesis. We provide mechanistic evidence that NEAT1 promotes ATR signaling in response to replication stress and is thereby engaged in a negative feedback loop that attenuates oncogene-dependent activation of p53. NEAT1 targeting in established human cancer cell lines induced synthetic lethality with genotoxic chemotherapeutics, including PARP inhibitors, and nongenotoxic activation of p53. This study establishes a key genetic link between NEAT1 paraspeckles, p53 biology and tumorigenesis and identifies NEAT1 as a promising target to enhance sensitivity of cancer cells to both chemotherapy and p53 reactivation therapy. PMID- 27376579 TI - Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice. AB - Age-related changes in the niche have long been postulated to impair the function of somatic stem cells. Here we demonstrate that the aged stem cell niche in skeletal muscle contains substantially reduced levels of fibronectin (FN), leading to detrimental consequences for the function and maintenance of muscle stem cells (MuSCs). Deletion of the gene encoding FN from young regenerating muscles replicates the aging phenotype and leads to a loss of MuSC numbers. By using an extracellular matrix (ECM) library screen and pathway profiling, we characterize FN as a preferred adhesion substrate for MuSCs and demonstrate that integrin-mediated signaling through focal adhesion kinase and the p38 mitogen activated protein kinase pathway is strongly de-regulated in MuSCs from aged mice because of insufficient attachment to the niche. Reconstitution of FN levels in the aged niche remobilizes stem cells and restores youth-like muscle regeneration. Taken together, we identify the loss of stem cell adhesion to FN in the niche ECM as a previously unknown aging mechanism. PMID- 27376581 TI - In the Wake of Orlando - Taking Steps against Gun Violence. PMID- 27376582 TI - Beyond Bathrooms--Meeting the Health Needs of Transgender People. PMID- 27376583 TI - Thrombalexins: Cell-Localized Inhibition of Thrombin and Its Effects in a Model of High-Risk Renal Transplantation. AB - Allograft transplantation into sensitized recipients with antidonor antibodies results in accelerated antibody-mediated rejection (AMR), complement activation, and graft thrombosis. We have developed a membrane-localizing technology of wide applicability that enables therapeutic agents, including anticoagulants, to bind to cell surfaces and protect the donor endothelium. We describe here how this technology has been applied to thrombin inhibitors to generate a novel class of drugs termed thrombalexins (TLNs). Using a rat model of hyperacute rejection, we investigated the potential of one such inhibitor (thrombalexin-1 [TLN-1]) to prevent acute antibody-mediated thrombosis in the donor organ. TLN-1 alone was able to reduce intragraft thrombosis and significantly delay rejection. The results confirm a pivotal role for thrombin in AMR in vivo. This approach targets donor organs rather than the recipient and is intended to be directly translatable to clinical use. PMID- 27376584 TI - Protein-retention expansion microscopy of cells and tissues labeled using standard fluorescent proteins and antibodies. AB - Expansion microscopy (ExM) enables imaging of preserved specimens with nanoscale precision on diffraction-limited instead of specialized super-resolution microscopes. ExM works by physically separating fluorescent probes after anchoring them to a swellable gel. The first ExM method did not result in the retention of native proteins in the gel and relied on custom-made reagents that are not widely available. Here we describe protein retention ExM (proExM), a variant of ExM in which proteins are anchored to the swellable gel, allowing the use of conventional fluorescently labeled antibodies and streptavidin, and fluorescent proteins. We validated and demonstrated the utility of proExM for multicolor super-resolution (~70 nm) imaging of cells and mammalian tissues on conventional microscopes. PMID- 27376586 TI - Autofluorescent gelatin nanoparticles as imaging probes to monitor matrix metalloproteinase metabolism of cancer cells. AB - In this paper, autofluorescent gelatin nanoparticles were synthesized as matrix metalloproteinase (MMP) responsive probes for cancer cell imaging. A modified two step desolvation method was employed to generate these nanoparticles whose size was controllable and had stable autofluorescence. As glutaraldehyde was introduced as the crosslinking agent, the generation of Schiff base (C?N) and double carbon bond (C?C) between glutaraldehyde and gelatin endowed these gelatin nanoparticles distinct autofluorescence. Considering MMPs were usually overexpressed on the surface of cancer cells and they had degradation ability toward gelatin, we utilized these nanoparticles as imaging probes to responsively monitor the MMP metabolism of cancer cells according to the luminance change. As fluorescent probes, these nanoparticles had facile synthesis procedure and good biocompatibility, and provided a smart strategy to monitor cancer cell behaviors. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2854-2860, 2016. PMID- 27376585 TI - Large-scale phenome analysis defines a behavioral signature for Huntington's disease genotype in mice. AB - Rapid technological advances for the frequent monitoring of health parameters have raised the intriguing possibility that an individual's genotype could be predicted from phenotypic data alone. Here we used a machine learning approach to analyze the phenotypic effects of polymorphic mutations in a mouse model of Huntington's disease that determine disease presentation and age of onset. The resulting model correlated variation across 3,086 behavioral traits with seven different CAG-repeat lengths in the huntingtin gene (Htt). We selected behavioral signatures for age and CAG-repeat length that most robustly distinguished between mouse lines and validated the model by correctly predicting the repeat length of a blinded mouse line. Sufficient discriminatory power to accurately predict genotype required combined analysis of >200 phenotypic features. Our results suggest that autosomal dominant disease-causing mutations could be predicted through the use of subtle behavioral signatures that emerge in large-scale, combinatorial analyses. Our work provides an open data platform that we now share with the research community to aid efforts focused on understanding the pathways that link behavioral consequences to genetic variation in Huntington's disease. PMID- 27376587 TI - The effects of napping on the risk of hypertension: a systematic review and meta analysis. AB - OBJECTIVE: The risk of hypertension in adults who regularly take a nap is controversial. The objective of this meta-analysis was to assess the associations between napping and hypertension. METHODS: A literature search was performed using MEDLINE, EMbase and The Cochrane Database of Systematic Reviews from inception through October, 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risk of hypertension in individuals who regularly take nap were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Nine observational studies with 112,267 individuals were included in the analysis to assess the risk of hypertension in nappers. The pooled RR of hypertension in nappers was 1.13 with 95% CI (0.98 to 1.30). When meta-analysis was limited only to studies assessing the risk of hypertension in daytime nappers, the pooled RR of hypertension was 1.19 with 95% CI (1.06 to 1.35). The data on association between nighttime napping in individuals who work night shift and hypertension were limited, only one observational study reported reduced risk of hypertension in nighttime nappers with odds ratio of 0.79 with 95% CI (0.63 to 1.00). CONCLUSIONS: Our meta-analysis demonstrates a significant association between daytime napping and hypertension. Future study is needed to assess the potential benefits of HTN screening for daytime nappers. PMID- 27376588 TI - The bicoid mRNA localization factor Exuperantia is an RNA-binding pseudonuclease. AB - Anterior patterning in Drosophila is mediated by the localization of bicoid (bcd) mRNA at the anterior pole of the oocyte. Exuperantia (Exu) is a putative exonuclease (EXO) associated with bcd and required for its localization. We present the crystal structure of Exu, which reveals a dimeric assembly with each monomer consisting of a 3'-5' EXO-like domain and a sterile alpha motif (SAM) like domain. The catalytic site is degenerate and inactive. Instead, the EXO-like domain mediates dimerization and RNA binding. We show that Exu binds RNA directly in vitro, that the SAM-like domain is required for RNA binding activity and that Exu binds a structured element present in the bcd 3' untranslated region with high affinity. Through structure-guided mutagenesis, we show that Exu dimerization is essential for bcd localization. Our data demonstrate that Exu is a noncanonical RNA-binding protein with EXO-SAM-like domain architecture that interacts with its target RNA as a homodimer. PMID- 27376589 TI - Free backbone carbonyls mediate rhodopsin activation. AB - Conserved prolines in the transmembrane helices of G-protein-coupled receptors (GPCRs) are often considered to function as hinges that divide the helix into two segments capable of independent motion. Depending on their potential to hydrogen bond, the free C=O groups associated with these prolines can facilitate conformational flexibility, conformational switching or stabilization of the receptor structure. To address the role of conserved prolines in family A GPCRs through solid-state NMR spectroscopy, we focus on bovine rhodopsin, a GPCR in the visual receptor subfamily. The free backbone C=O groups on helices H5 and H7 stabilize the inactive rhodopsin structure through hydrogen-bonds to residues on adjacent helices. In response to light-induced isomerization of the retinal chromophore, hydrogen-bonding interactions involving these C=O groups are released, thus facilitating repacking of H5 and H7 onto the transmembrane core of the receptor. These results provide insights into the multiple structural and functional roles of prolines in membrane proteins. PMID- 27376590 TI - Effects of omitting elective neck irradiation to nodal Level IB in nasopharyngeal carcinoma patients with negative Level IB lymph nodes treated by intensity modulated radiotherapy: a Phase 2 study. AB - OBJECTIVE: To investigate the need for elective neck irradiation (ENI) to nodal Level IB in patients with nasopharyngeal carcinoma (NPC) with negative Level IB lymph nodes (IB-negative) treated by intensity-modulated radiotherapy (IMRT). METHODS: We conducted a Phase 2 prospective study in 123 newly diagnosed IB negative patients with NPC treated by IMRT, who met at least 1 of the following criteria: (1) unilateral or bilateral Level II involvement with 1 of the following: Level IIA involvement or any Level II node >=2 cm/with extracapsular spread; (2) >=2 unilateral node-positive regions. Bilateral Level IB nodes were not contoured as part of the treatment target and treated electively. Level IB regional recurrence rate; pattern of treatment failure; 3-year overall survival (3y-OS), 3-year local control (3y-LC) and 3-year regional control (3y-RC) rates; toxicities; and dosimetric data for planning target volumes, organs at risk, Level IB and submandibular glands (SMGs) were evaluated. RESULTS: Two patients developed failures at Level IB (1.6%). The 3y-LC, 3y-RC and 3y-OS rates were 93.5%, 93.5% and 78.0%, respectively. Bilateral Level IB received unplanned high dose irradiation with a mean dose (Dmean) >=50 Gy in 60% of patients. The average Dmean of bilateral SMGs was approximately 53 Gy. CONCLUSION: ENI to Level IB may be unnecessary in IB-negative patients with NPC treated by IMRT. A further Phase 3 study is warranted. ADVANCES IN KNOWLEDGE: Based on the results of this first Phase 2 study, we suggest omitting ENI to Level IB in Ib-negative patients with NPC with extensive nodal disease treated by IMRT. PMID- 27376591 TI - Animal models of chronic pain: Advances and challenges for clinical translation. AB - Chronic pain is a global problem that has reached epidemic proportions. An estimated 20% of adults suffer from pain, and another 10% are diagnosed with chronic pain each year (Goldberg and McGee, ). Despite the high prevalence of chronic pain (an estimated 1.5 billion people are afflicted worldwide), much remains to be understood about the underlying causes of this condition, and there is an urgent requirement for better pain therapies. The discovery of novel targets and the development of better analgesics rely on an assortment of preclinical animal models; however, there are major challenges to translating discoveries made in animal models to realized pain therapies in humans. This review discusses common animal models used to recapitulate clinical chronic pain conditions (such as neuropathic, inflammatory, and visceral pain) and the methods for assessing the sensory and affective components of pain in animals. We also discuss the advantages and limitations of modeling chronic pain in animals as well as highlighting strategies for improving the predictive validity of preclinical pain studies. (c) 2016 Wiley Periodicals, Inc. PMID- 27376592 TI - Optimisation of percutaneous coronary intervention: indispensables for bioresorbable scaffolds. AB - INTRODUCTION: With new developments in percutaneous coronary intervention (PCI), such as the introduction of bioresorbable scaffolds (BRS), percutaneous treatment of coronary artery diseases has entered a new era. Without metallic remnants, BRSs appear able to overcome several limitations of the existing metallic stents and provide a physiologic treatment of coronary artery pathology. AREAS COVERED: BRS have different mechanical properties compared to the traditional metallic stents that should be taken into account during their implantation. Lesion selection, device sizing and satisfied pre-dilatation should be implemented prudently. Although intravascular imaging is not mandatory for the implantation of BRSs it may have a value in optimizing device deployment assess final results and reduce the risk of device related adverse events such as re-stenosis, or scaffold thrombosis. This review aims to reveal the crucial points about the methods of optimization in each steps of BRS implantation. Expert commentary: The target lesions for BRS should be selected meticulously. Pre-dilatation, post dilatation and intra-vascular imaging techniques should be implemented appropriately to avoid undesirable events after scaffold implantation. PMID- 27376593 TI - "Whenever they cry, I cry with them": Reciprocal relationships and the role of ethics in a verbal autopsy study in Papua New Guinea. AB - Verbal autopsy (VA) methods usually involve an interview with a recently bereaved individual to ascertain the most probable cause of death when a person dies outside of a hospital and/or did not receive a reliable death certificate. A number of concerns have arisen around the ethical and social implications of the use of these methods. In this paper we examine these concerns, looking specifically at the cultural factors surrounding death and mourning in Papua New Guinea, and the potential for VA interviews to cause emotional distress in both the bereaved respondent and the VA fieldworker. Thirty one semi-structured interviews with VA respondents, the VA team and community relations officers as well as observations in the field and team discussions were conducted between June 2013 and August 2014. While our findings reveal that VA participants were often moved to cry and feel sad, they also expressed a number of ways they benefited from the process, and indeed welcomed longer transactions with the VA interviewers. Significantly, this paper highlights the ways in which VA interviewers, who have hitherto been largely neglected in the literature, navigate transactions with the participants and make everyday decisions about their relationships with them in order to ensure that they and VA interviews are accepted by the community. The role of the VA fieldworker should be more carefully considered, as should the implications for training and institutional support that follow. PMID- 27376595 TI - "It's not if I get cancer, it's when I get cancer": BRCA-positive patients' (un)certain health experiences regarding hereditary breast and ovarian cancer risk. AB - RATIONALE: Women with a harmful mutation in the BReast CAncer (BRCA) gene are at significantly increased risk of developing hereditary breast and ovarian cancer (HBOC) during their lifetime, compared to those without. Such patients-with a genetic predisposition to develop cancer but who have not yet been diagnosed with cancer-live in a constant state of uncertainty and wonder not if they might get cancer but when. OBJECTIVE: Framed by uncertainty management theory, the purpose of this study was to explore BRCA-positive patients' health experiences after testing positive for the BRCA genetic mutation, specifically identifying their sources of uncertainty. METHODS: Thirty-four, qualitative interviews were conducted with female patients. Participants responded to online research postings on the non-profit organization Facing Our Risk of Cancer Empowered's (FORCE) message board and social media pages as well as HBOC-specific Facebook groups. The interview data were coded using the constant comparison method. RESULTS: Two major themes representing BRCA-positive patients' sources of uncertainty regarding their genetic predisposition and health experiences emerged from the data. Medical uncertainty included the following three subthemes: the unknown future, medical appointments, and personal cancer scares. Familial uncertainty encompassed the subthemes traumatic family cancer memories and motherhood. CONCLUSIONS: Overall, the study supports and extends existing research on uncertainty-revealing uncertainty is inherent in BRCA-positive patients' health experiences-and offers new insight regarding uncertainty management and HBOC risk. PMID- 27376594 TI - Can cash transfers improve determinants of maternal mortality? Evidence from the household and community programs in Indonesia. AB - Despite global efforts in maternal health, 303,000 maternal deaths still occurred globally in 2015. One explanation is a considerable inequality in maternal mortality and the sources such as nutritional status and health utilization. One strategy to fight health inequality due to poverty is conditional cash transfer (CCT). Taking advantage of two large clustered-randomized trials in Indonesia from 2007 to 2009, this paper provides evidence on the effects of household cash transfers (PKH) and community cash transfers (Generasi) on determinants of maternal mortality. The sample sizes are 14,000 households for PKH and 12,000 households for Generasi. After two years of implementation, difference-in differences (DID) analyses show that the two programs can improve determinants of maternal mortality with Generasi provides positive impact in some aspects of determinants, but PKH does not. Generasi improves maternal health knowledge, reduces financial barriers to accessing health services and improves utilization of health services, increases utilization among higher-risk women, improves posyandu equipment, and increases nutritional intake. As for PKH, evidence shows its strongest effects only on utilization of health services. Both programs, however, are unlikely to have a large effect on maternal mortality due to design and implementation issues that might significantly reduce program effectiveness. While the programs improved utilization, they did so at community-based facilities not equipped with emergency obstetric care. In the midst of popularity of household cash transfer, our results show that community cash transfer offers a viable policy alternative to improve the determinants of maternal mortality by allowing more flexibility in activities and at lower cost by monitoring at community level. PMID- 27376597 TI - Survival of Sickest. PMID- 27376598 TI - Is it Right Time to Introduce Mumps Vaccine in Indias Universal Immunization Program? AB - Measles, mumps and rubella are vaccine preventable diseases. However, morbidity and mortality due to these diseases remain largely unnoticed in India. Measles has received much attention; mumps and rubella still need to garner attention. According to the World Health Organization, near-elimination of mumps could be achieved by maintaining high vaccine coverage using a two-dose strategy. However, Government of India has not yet decided on mumps vaccine. In this review, we have reviewed sero-prevalence studies, vaccine studies, outbreak investigations, virus isolation and virus genotyping studies on mumps. Overall, mumps seems to be a significant public health problem in India, but does not garner attention due to the absence of a surveillance and documentation system. Thus, inclusion of mumps antigen in the Universal immunization program would have added advantages, the economic burden imposed by the cost of the vaccine offset by a reduction in disease burden. PMID- 27376596 TI - Microelectrode Arrays of Diamond-Insulated Graphitic Channels for Real-Time Detection of Exocytotic Events from Cultured Chromaffin Cells and Slices of Adrenal Glands. AB - A microstructured graphitic 4 * 4 multielectrode array was embedded in a single crystal diamond substrate (4 * 4 MUG-SCD MEA) for real-time monitoring of exocytotic events from cultured chromaffin cells and adrenal slices. The current approach relies on the development of a parallel ion beam lithographic technique, which assures the time-effective fabrication of extended arrays with reproducible electrode dimensions. The reported device is suitable for performing amperometric and voltammetric recordings with high sensitivity and temporal resolution, by simultaneously acquiring data from 16 rectangularly shaped microelectrodes (20 * 3.5 MUm(2)) separated by 200 MUm gaps. Taking advantage of the array geometry we addressed the following specific issues: (i) detect both the spontaneous and KCl evoked secretion simultaneously from several chromaffin cells directly cultured on the device surface, (ii) resolve the waveform of different subsets of exocytotic events, and (iii) monitoring quantal secretory events from thin slices of the adrenal gland. The frequency of spontaneous release was low (0.12 and 0.3 Hz, respectively, for adrenal slices and cultured cells) and increased up to 0.9 Hz after stimulation with 30 mM KCl in cultured cells. The spike amplitude as well as rise and decay time were comparable with those measured by carbon fiber microelectrodes and allowed to identify three different subsets of secretory events associated with "full fusion" events, "kiss-and-run" and "kiss-and-stay" exocytosis, confirming that the device has adequate sensitivity and time resolution for real-time recordings. The device offers the significant advantage of shortening the time to collect data by allowing simultaneous recordings from cell populations either in primary cell cultures or in intact tissues. PMID- 27376599 TI - Vitamin D in Critical Illness: Not a Panacea for All Ills! PMID- 27376600 TI - Improving Access and Reducing Childhood Deaths due to Pneumonia. PMID- 27376601 TI - Vitamin D Deficiency and Parathyroid Response in Critically-ill Children: Association with Illness Severity and Clinical Outcomes. AB - OBJECTIVE: To determine the prevalence of vitamin D deficiency in critically ill children, and to study its association with parathyroid response, severity of illness and clinical outcomes. DESIGN: Prospective observational study. SETTING: Medical Pediatric Intensive Care Unit of a tertiary care centre of Northern India. PARTICIPANTS: 154 children in-patients: August 2011-January 2013. MAIN OUTCOME MEASURES: Vitamin D deficient children were (serum 25-hydroxy vitamin D <20 ug/mL) divided into parathyroid-responder [serum parathyroid hormone >65 pg/mL with 25(OH)D<20 ug/mL and/or calcium corrected for albumin <8.5 mg/dL] and non parathyroid-responder. Illness severity was assessed by Pediatric Index of Mortality-2 (PIM-2) score at admission. Biochemical parameters, illness severity scores and clinical outcomes were compared between parathyroid-responders and non parathyroid-responders. RESULTS: Vitamin D deficiency and hypocalcemia were observed in 125 (83.1%) and 91 (59%) children, respectively at admission. There were no differences in illness severity score at admission, mortality rate and length of stay between vitamin D-deficient children and 19.8% of non-vitamin D deficient children. Among Vitamin D-deficient children, parathyroid-responders had higher PIM-2 score at admission compared to non-parathyroid-responder [12.8 (7.4,20.6) vs. 6.5 (2.5,12.2), P=0.01]. However, there were no differences in other clinical outcomes between two groups. CONCLUSION: Critically ill children have high prevalence of vitamin D deficiency. Parathyroid gland response secondary to hypocalcemia or vitamin D defiency is impaired in critical illness. PMID- 27376602 TI - Cognitive Functions and Psychological Problems in Children with Sickle Cell Anemia. AB - OBJECTIVE: To study the cognitive functions and psychological problems in children with Sickle cell anemia (SCA). METHODS: Children with SCA were compared with an age, sex- and community- matched control group of children with no SCA. Malins Intelligence Scale for Indian children, modified PGI memory scale, and Childhood Psychopathology Measurement Schedule were used to assess cognitive functions and psychological problems. RESULTS: Verbal quotient, performance quotient and intelligence quotient in SCA group were 77, 81, 78, respectively versus 92, 95, 93, respectively in non-SCA group (P <0.001). Borderline intellectual functioning and mild mental retardation were more common in SCA (70< and 16<, respectively). Children with SCA had impaired attention, concentration and working memory and more behavior problems compared to children without SCA. CONCLUSION: Cognitive functions are impaired in children with SCA and they have more psychological problems. Facilities for early identification and remediation of psychological and intellectual problems should be incorporated with health care services for children with sickle cell anemia. PMID- 27376603 TI - Oral Antibiotics for Community acquired Pneumonia with Chest indrawing in Children Aged Below Five Years: A Systematic Review. AB - OBJECTIVE: To determine the efficacy of oral antibiotics in under-five children with pneumonia and chest indrawing. METHODS: We included controlled clinical trials (randomized or quasi randomized) that compared the efficacy of oral antibiotics versus parenteral antibiotics for treatment of community acquired pneumonia with chest indrawing (severe pneumonia as defined by the World Health Organizations guidelines) in children below 60 months of age. Data were extracted and managed using RevMan software. Main outcome variables were: treatment failure rate, relapse rate, death rate, need for hospitalization, and severe adverse effects. RESULTS: We identified four randomized controlled trials involving 4400 children who were diagnosed to have severe pneumonia but were feeding well and not hypoxic. Baseline characteristics of children in the two treatment arms (oral and parenteral antibiotics) were similar. In two studies, oral antibiotics were administered on an ambulatory basis, while in two, oral antibiotics were used in hospitalized children. Failure rate in children receiving oral antibiotics was 13% (288/2208) while that in children receiving parenteral antibiotics was 13.8% (302/2183) (OR 0.93; 95% CI 0.78, 1.11). Failure rates were not affected by the type of oral antibiotic, or presence of wheeze. Relapse rates, hospitalization or serious adverse events were similar in the two groups. CONCLUSIONS: Children with tachypnea with chest indrawing without signs and symptoms of very severe pneumonia may be treated with oral antibiotics. PMID- 27376604 TI - Teaching and Assessing Communication Skills in Medical Undergraduate Training. AB - Good communication skills are essential for an optimal doctor-patient relationship, and also contribute to improved health outcomes. Although the need for training in communication skills is stated as a requirement in the 1997 Graduate Medical Education Regulations of the Medical Council of India, formal training in these skills has been fragmentary and non-uniform in most Indian curricula. The Vision 2015 document of the Medical Council of India reaffirms the need to include training in communication skills in the MBBS curriculum. Training in communication skills needs approaches which are different from that of teaching other clinical subjects. It is also a challenge to ensure that students not only imbibe the nuances of communication and interpersonal skills, but adhere to them throughout their careers. This article addresses the possible ways of standardizing teaching and assessment of communication skills and integrating them into the existing curriculum. PMID- 27376605 TI - Hemophagocytic Lymphohistiocytosis in a Young Child. AB - Hemophagocytic lymphohistiocytosis (HLH) is a multisystem disorder mediated by cytokine storm and is characterized by fever, pancytopenia and organomegaly coupled with laboratory features like hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia and transaminitis. Etiology can be genetic or acquired such as infections, malignancy and autoimmune disorders. Diagnosis, identification of underlying etiology and management of HLH remain tough clinical puzzles to sort out for the managing physician. We report a clinico-pathological conference of a three-year-old boy who had such a presentation and succumbed during the hospital stay. PMID- 27376606 TI - Sharing Clinical Experience with the Scientific Community: How to Write a Case Report? PMID- 27376607 TI - Pediatric Tuberculosis, What has Changed. PMID- 27376608 TI - Can We Predict Antibiotic-resistance in Urinary Tract Infection: Evidence-based Medicine Viewpoint. PMID- 27376609 TI - Can We Predict Antibiotic-resistance in Urinary Tract Infection?: Pediatric Nephrologists Viewpoint. PMID- 27376610 TI - Blue Rubber Bleb Nevus Syndrome with Musculo-skeletal Involvement and Pulmonary Stenosis. AB - BACKGROUND: Blue rubber bleb nevus syndrome is a rare clinical entity. CASE CHARACTERISTICS: A 13-year-old Indian boy presented with characteristic cutaneous lesions, gastrointestinal malformations, skeletal involvement and pulmonary stenosis. OBSERVATIONS: Diagnosis was confirmed on skin biopsy, radiographic evaluation, colonoscopy and echocardiography. Echocardiography revealed pulmonary stenosis, an association hitherto undescribed. MESSAGE: Detailed evaluation in a patient of blue rubber bleb nerves syndrome is mandatory. PMID- 27376611 TI - X-linked Congenital Adrenal Hypoplasia with a Novel NR0B1/DAX Gene Mutation. AB - BACKGROUND: The etiology of primary adrenal insufficiency has implications for further management of the condition. CASE CHARACTERISTICS: A 5-year-old boy presented in adrenal crisis with glucocorticoid and mineralocorticoid deficiency. OBSERVATION: Investigations confirmed primary adrenal insufficiency and ruled out the common etiologies. Genetic testing identified a novel NR0B1/DAX gene mutation. MESSAGE: A genetic diagnosis in children with primary adrenal insufficiency is useful to provide genetic counselling. PMID- 27376612 TI - Generics Drugs,Are They Really Equivalent to Brands. PMID- 27376613 TI - Effective Prevention of Parent-to- Child Transmission of HIV. PMID- 27376614 TI - Effective Prevention of Parent-to-Child Transmission of HIV: Authors Reply. PMID- 27376615 TI - Nasopharyngeal Carriage of Organisms in Children With Severe Pneumonia. PMID- 27376616 TI - Nasopharyngeal Carriage of Organisms in Children With Severe Pneumonia: Authors reply. PMID- 27376617 TI - Centralized Newborn Hearing screening in Mumbai: Success or Failure? PMID- 27376618 TI - Transfusion-associated Necrotizing Enterocolitis. PMID- 27376619 TI - Transfusion-associated Necrotizing Enterocolitis: Authors Reply. PMID- 27376620 TI - Spatial and temporal variability of aerobic anoxygenic photoheterotrophic bacteria along the east coast of Australia. AB - Aerobic Anoxygenic Phototrophic Bacteria (AAnPB) are ecologically important microorganisms, widespread in oceanic photic zones. However, the key environmental drivers underpinning AAnPB abundance and diversity are still largely undefined. The temporal patterns in AAnPB dynamics at three oceanographic reference stations spanning at approximately 15 degrees latitude along the Australian east coast were examined. AAnPB abundance was highly variable, with pufM gene copies ranging from 1.1 * 102 to 1.4 * 105 ml-1 and positively correlated with day length and solar radiation. pufM gene Miseq sequencing revealed that the majority of sequences were closely related to those obtained previously, suggesting that key AAnPB groups are widely distributed across similar environments globally. Temperature was a major structuring factor for AAnPB assemblages across large spatial scales, correlating positively with richness and Gammaproteobacteria (phylogroup K) abundance but negatively with Roseobacter-clade (phylogroup E) abundance, with temperatures between 16 degrees C and 18 degrees C identified as a potential transition zone between these groups. Network analysis revealed that discrete AAnPB populations exploit specific niches defined by varying temperature, light and nutrient conditions in the Tasman Sea system, with evidence for both niche sharing and partitioning amongst closely related operational taxonomic units. PMID- 27376622 TI - Buprenorphine dosing choices in specific populations: review of expert opinion. AB - INTRODUCTION: Treatment of opioid dependence with buprenorphine improves outcomes. Typical dosing ranges for all patients from clinical evidence and as defined in the product information are wide. For specific groups with complex clinical scenarios, there is no clear consensus on dosing choices to achieve best possible outcomes. AREAS COVERED: The doses of buprenorphine used in 6 European countries was reviewed. A review of published evidence supported rapid induction with buprenorphine and the benefits of higher doses but did not identify clearly useful guidance on dosing choices for groups with complex clinical scenarios. An expert group of physicians with experience in addiction care participated in a discussion meeting to share clinical practice experience and develop a consensus on dosing choices. EXPERT OPINION: There was general agreement that treatment outcomes can be improved by optimising buprenorphine doses in specific subgroups. Specific groups in whom buprenorphine doses may be too low and who could have better outcomes with optimised dosing were identified on the basis of clinical practice experience. These groups include people with severe addiction, high tolerance to opioids, and psychiatric comorbidities. In these groups it is recommended to review dosing choices to ensure buprenorphine dosing is sufficient. PMID- 27376623 TI - A Hydrophobic Metal-Organic Framework Based on Cubane-Type [Co4 (MU3 -F)3 (MU3 SO4 )](3+) Clusters for Gas Storage and Adsorption Selectivity of Benzene over Cyclohexane. AB - Hydrophobic metal-organic frameworks (MOFs) not only have high water stability, but also exhibit high adsorption capacity towards organic molecules, in particular hydrocarbons. Herein we report a rare metal fluoride organic framework MFOF-1 with high hydrophobicity, which is constructed from unprecedented fluoride and sulfate-bridged cubane-type tetranuclear cobalt clusters. MFOF-1 consists of three types of polyhedral cages with face-sharing configurations, and possesses a novel (3,9)-connected 3D+3D->3D self-interpenetrating array or the rare pyr topology. MFOF-1 shows high thermal stability and high stability in water and even acid/base aqueous solutions, and exhibits rather high H2 and CO2 storage capacities at ambient pressure. Remarkably, MFOF-1 shows little adsorption of water but considerably high uptakes of methanol, n-hexane, cyclohexane, and benzene, and exhibits a certain degree of adsorption selectivity of benzene over cyclohexane. PMID- 27376621 TI - The antioxidant edaravone prevents cardiac dysfunction by suppressing oxidative stress in type 1 diabetic rats and in high-glucose-induced injured H9c2 cardiomyoblasts. AB - Edaravone, a radical scavenger, has been recognized as a potential protective agent for cardiovascular diseases. However, little is known about the effect of edaravone in cardiac complications associated with diabetes. Here, we have demonstrated that edaravone prevents cardiac dysfunction and apoptosis in the streptozotocin-induced type 1 diabetic rat heart. Mechanistic studies revealed that edaravone treatment improved cardiac function and restored superoxide dismutase levels. In addition, treatment of diabetic animals by edaravone increased protein expressions of sirtuin-1 (SIRT-1), peroxisome proliferator activated receptor gamma coactivator alpha (PGC-1alpha), nuclear factor like-2 (NRF-2), and B cell lymphoma 2 (Bcl-2), and reduced protein expressions of Bax and Caspase-3 compared to the control group. High glucose incubation resulted in the production of reactive oxygen species (ROS) and cell death. Treatment of high glucose-incubated H9c2 cells by edaravone reduced ROS production and cell death. In addition, the treatment of high-glucose-incubated H9c2 cells by edaravone increased the activity of antioxidative stress by increasing SIRT-1, PGC-1alpha, and NRF-2, and this treatment also reduced apoptosis by increasing Bcl-2 expression and reducing Bax and Caspase-3 expressions. Knockdown SIRT-1 with small interferer RNA abolished the effects of edaravone. Overall, our data demonstrated that edaravone may be an effective agent against the development of diabetic cardiomyopathy. PMID- 27376624 TI - Low-carbohydrate diets increase LDL-cholesterol, and thereby indicate increased risk of CVD. PMID- 27376626 TI - Global consensus statement on menopausal hormone therapy - an update. PMID- 27376625 TI - Enantioselective Allylic C-H Oxidation of Terminal Olefins to Isochromans by Palladium(II)/Chiral Sulfoxide Catalysis. AB - The enantioselective synthesis of isochroman motifs has been accomplished by palladium(II)-catalyzed allylic C-H oxidation from terminal olefin precursors. Critical to the success of this goal was the development and utilization of a novel chiral aryl sulfoxide-oxazoline (ArSOX) ligand. The allylic C-H oxidation reaction proceeds with the broadest scope and highest levels of asymmetric induction reported to date (avg. 92 % ee, 13 examples with greater than 90 % ee). PMID- 27376627 TI - Probing the Microporous Structure of Silica Shell Via Aggregation-Induced Emission in Au(I)-Thiolate@SiO2 Nanoparticle. AB - An efficient method to investigate the window size of the silica shell generated via the classical Stober method is reported by making use of the unique aggregation-induced emission property of Au(I)-thiolate complexes, which can precisely probe the porosity of the silica shell in Au(I)-thiolate@SiO2 nanoparticles. PMID- 27376628 TI - A Comparison Study of Frying Conditions on Furan Formation in 3 Potato Varieties. AB - Furan, a typical food contaminant formed by heating process, is classified as a possible carcinogen to humans. Many factors lead to the formation of furan in food processing. In our present study, 3 potato varieties, white potato, sweet potato, and purple potato were selected to investigate the effect of thermal processing temperature and time on furan formation. The results showed that the formation of furan was highly correlated with frying temperature and time. Among the 3 potato varieties, sweet potato resulted in the highest furan concentration when fried at 200 degrees C for 5 min. In addition, the frying temperature and time also influenced the water activity and the color of the 3 kinds of potato slices, which had significant correlation with the formation of furan. Furan concentration decreased along with the increasing of water activity in the 3 potato varieties and the changes presented regression relationships. Meanwhile, there was an inverse correlation between furan content and color changes in the 3 potato varieties. The level of furan decreased as total color changes (DeltaE) increased and the changes also presented regression relationships. These results could be used to estimate the possibility of furan formation in the 3 varieties of potato slices systems. PMID- 27376629 TI - Continuous counter-current chromatography for capture and polishing steps in biopharmaceutical production. AB - The economic advantages of continuous processing of biopharmaceuticals, which include smaller equipment and faster, efficient processes, have increased interest in this technology over the past decade. Continuous processes can also improve quality assurance and enable greater controllability, consistent with the quality initiatives of the FDA. Here, we discuss different continuous multi column chromatography processes. Differences in the capture and polishing steps result in two different types of continuous processes that employ counter-current column movement. Continuous-capture processes are associated with increased productivity per cycle and decreased buffer consumption, whereas the typical purity-yield trade-off of classical batch chromatography can be surmounted by continuous processes for polishing applications. In the context of continuous manufacturing, different but complementary chromatographic columns or devices are typically combined to improve overall process performance and avoid unnecessary product storage. In the following, these various processes, their performances compared with batch processing and resulting product quality are discussed based on a review of the literature. Based on various examples of applications, primarily monoclonal antibody production processes, conclusions are drawn about the future of these continuous-manufacturing technologies. PMID- 27376630 TI - Extensional Flow-Induced Dynamic Phase Transitions in Isotactic Polypropylene. AB - With a combination of fast extension rheometer and in situ synchrotron radiation ultra-fast small- and wide-angle X-ray scattering, flow-induced crystallization (FIC) of isotactic polypropylene (iPP) is studied at temperatures below and above the melting point of alpha crystals (Tmalpha). A flow phase diagram of iPP is constructed in strain rate-temperature space, composing of melt, non-crystalline shish, alpha and alpha&beta coexistence regions, based on which the kinetic and dynamic competitions among these four phases are discussed. Above Tmalpha , imposing strong flow reverses thermodynamic stabilities of the disordered melt and the ordered phases, leading to the occurrence of FIC of beta and alpha crystals as a dynamic phase transition. Either increasing temperature or stain rate favors the competiveness of the metastable beta over the stable alpha crystals, which is attributed to kinetic rate rather than thermodynamic stability. The violent competitions among four phases near the boundary of crystal-melt may frustrate crystallization and result in the non-crystalline shish winning out. PMID- 27376631 TI - Editorial Comment. PMID- 27376633 TI - Molecular design driving tetraporphyrin self-assembly on graphite: a joint STM, electrochemical and computational study. AB - Tuning the intermolecular interactions among suitably designed molecules forming highly ordered self-assembled monolayers is a viable approach to control their organization at the supramolecular level. Such a tuning is particularly important when applied to sophisticated molecules combining functional units which possess specific electronic properties, such as electron/energy transfer, in order to develop multifunctional systems. Here we have synthesized two tetraferrocene porphyrin derivatives that by design can selectively self-assemble at the graphite/liquid interface into either face-on or edge-on monolayer-thick architectures. The former supramolecular arrangement consists of two-dimensional planar networks based on hydrogen bonding among adjacent molecules whereas the latter relies on columnar assembly generated through intermolecular van der Waals interactions. Scanning Tunneling Microscopy (STM) at the solid-liquid interface has been corroborated by cyclic voltammetry measurements and assessed by theoretical calculations to gain multiscale insight into the arrangement of the molecule with respect to the basal plane of the surface. The STM analysis allowed the visualization of these assemblies with a sub-nanometer resolution, and cyclic voltammetry measurements provided direct evidence of the interactions of porphyrin and ferrocene with the graphite surface and offered also insight into the dynamics within the face-on and edge-on assemblies. The experimental findings were supported by theoretical calculations to shed light on the electronic and other physical properties of both assemblies. The capability to engineer the functional nanopatterns through self-assembly of porphyrins containing ferrocene units is a key step toward the bottom-up construction of multifunctional molecular nanostructures and nanodevices. PMID- 27376632 TI - Threonine 80 phosphorylation of non-structural protein 1 regulates the replication of influenza A virus by reducing the binding affinity with RIG-I. AB - Influenza A virus evades host antiviral defense through hijacking innate immunity by its non-structural protein 1 (NS1). By using mass spectrometry, threonine 80 (T80) was identified as a novel phosphorylated residue in the NS1 of the influenza virus A/WSN/1933(H1N1). By generating recombinant influenza viruses encoding NS1 T80 mutants, the roles of this phosphorylation site were characterized during viral replication. The T80E (phosphomimetic) mutant attenuated virus replication, whereas the T80A (non-phosphorylatable) mutant did not. Similar phenotypes were observed for these mutants in a mouse model experiment. In further study, the T80E mutant decreased the binding capacity between NS1 and viral nucleoprotein (NP), leading to impaired viral ribonucleoprotein (vRNP)-mediated viral transcription. The T80E mutant was also unable to inhibit interferon (IFN) production by reducing the binding affinity between NS1 and retinoic acid-induced gene 1 protein (RIG-I), causing attenuation of virus replication. Taken together, the present study reveals that T80 phosphorylation of NS1 reduced influenza virus replication through controlling RIG-I-mediated IFN production and vRNP activity. PMID- 27376634 TI - Meta-analysis of technology-assisted interventions for social anxiety disorder. AB - This meta-analysis investigated the efficacy of technology-assisted interventions for individuals with social anxiety disorder (SAD). A systematic literature search in the databases Medline, PsychInfo, and Web of Science revealed 37 randomized controlled trials (2991 participants) that were grouped into internet delivered cognitive behavior therapy (ICBT; 21 trials), virtual reality exposure therapy (VRET; 3 trials), and cognitive bias modification (CBM; 13 trials). Patients undergoing ICBT and VRET showed significantly less SAD symptoms at postassessment than passive control conditions (g=0.84 and 0.82, respectively). Compared to active control conditions, ICBT had a small advantage (g=0.38) and VRET showed comparable effects (p>0.05). CBM was not more effective than passive control conditions, except when delivered in the laboratory (g=0.35). While the efficacy of CBM was limited, substantial evidence for ICBT and preliminary evidence for VRET suggests that both can effectively reduce SAD symptoms indicating the potential of technology-assisted interventions for SAD. PMID- 27376635 TI - Mechanoreceptors of the ligaments and tendons around the knee. AB - Proprioceptive inputs from the joints and limbs arise from mechanoreceptors in the muscles, ligaments and tendons. The knee joint has a wide range of movements, and proper neuroanatomical organization is critical for knee stability. Four ligaments (the anterior (ACL) and posterior (PCL) cruciate ligaments and the medial (MCL) and lateral (LCL) collateral ligaments) and four tendons (the semitendinosus (STT), gracilis (GT), popliteal (PoT), and patellar (PaT) tendons) from eight fresh frozen cadavers were harvested. Each harvested tissue was divided into its bone insertion side and its tendinous part for immunohistochemical examination using S100 staining. Freeman-Wyke's classification was used to identify the mechanoreceptors. The mechanoreceptors were usually located close to the bone insertion. Free nerve endings followed by Ruffini endings were the most common mechanoreceptors overall. No Pacini corpuscles were observed; free nerve endings and Golgi-like endings were most frequent in the PCL (PCL-PaT: P = 0.0.1, PCL-STT: P = 0.00), and Ruffini endings in the popliteal tendon (PoT-PaT: P = 0.00, Pot-STT: P = 0.00, PoT-LCL: P = 0.00, PoT-GT: P = 0.00, PoT-ACL: P = 0.09). The cruciate ligaments had more mechanoreceptors than the medial structures (MS) or the patellar tendon (CR-Pat: P = 0.000, CR-MS: P = 0.01). The differences in mechanoreceptor distributions between the ligaments and tendons could reflect the different roles of these structures in the dynamic coordination of knee motion. Clin. Anat. 29:789-795, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27376636 TI - How are service users instructed to measure home furniture for provision of minor assistive devices? AB - PURPOSE: Measurements play a vital role in providing devices that meet the individual needs of users. There is increasing evidence of devices being abandoned. The reasons for this are complex but one key factor that plays a role in non-use of equipment is the lack of fit between the device, environment and person. In addition, the abandonment of devices can be seen as a waste of public money. The aim of this paper is to examine the type, the readability, and the content of existing guidance in relation to measuring home furniture. METHOD: An online national survey involving health and social care trusts in the UK. We conducted a synthesis of leaflets associated with measurement of furniture to identify existing guidance. The content and readability of this guidance was then evaluated. RESULTS: From the 325 responses received, 64 therapists reported using guidance. From the 13 leaflets that were analysed, 8 leaflets were found to meet Level 3 Adult Literacy Standards (age 9-11). There were differences in the way in which the measurement of furniture items occurred within the leaflets with no measurement guidance reported for baths. CONCLUSION: There is a need to standardize guidance to ensure that measurements are reliable. Implications for Rehabilitation Our research has highlighted the need to confirm and agree measurement techniques for home furniture in the provision of assistive devices. Inaccurate guidance can lead to abandonment of devices. Inaccurate guidance could prevent service users from not participating within the self-assessment process for devices. PMID- 27376637 TI - Particle therapy of moving targets-the strategies for tumour motion monitoring and moving targets irradiation. AB - Particle therapy of moving targets is still a great challenge. The motion of organs situated in the thorax and abdomen strongly affects the precision of proton and carbon ion radiotherapy. The motion is responsible for not only the dislocation of the tumour but also the alterations in the internal density along the beam path, which influence the range of particle beams. Furthermore, in case of pencil beam scanning, there is an interference between the target movement and dynamic beam delivery. This review presents the strategies for tumour motion monitoring and moving target irradiation in the context of hadron therapy. Methods enabling the direct determination of tumour position (fluoroscopic imaging of implanted radio-opaque fiducial markers, electromagnetic detection of inserted transponders and ultrasonic tumour localization systems) are presented. Attention is also drawn to the techniques which use external surrogate motion for an indirect estimation of target displacement during irradiation. The role of respiratory-correlated CT [four-dimensional CT (4DCT)] in the determination of motion pattern prior to the particle treatment is also considered. An essential part of the article is the review of the main approaches to moving target irradiation in hadron therapy: gating, rescanning (repainting), gated rescanning and tumour tracking. The advantages, drawbacks and development trends of these methods are discussed. The new accelerators, called "cyclinacs", are presented, because their application to particle therapy will allow making a breakthrough in the 4D spot scanning treatment of moving organs. PMID- 27376638 TI - Multilayer Dielectric Elastomers for Fast, Programmable Actuation without Prestretch. AB - A novel method for the fabrication of dielectric elastomer actuators (DEAs) combines acrylic polymers and single wall carbon nanotube network electrodes. DEAs made using this technique do not require prestretching, have extremely thin electrodes, and can be actuated at low voltage. The method is applied to create a multimorph device with nine actuation modes based on just four inputs. PMID- 27376639 TI - Pharmacokinetic patterns of risperidone-associated adverse drug reactions. AB - PURPOSE: The aim of the study was to investigate a correlation between plasma concentrations of risperidone (RIS), its active metabolite 9-hydroxyrisperidone (9-OH-RIS) and the active moiety (AM) (RIS + 9-OH-RIS), and adverse drug reactions (ADRs) in a naturalistic sample. METHODS: Plasma concentrations of RIS, 9-OH-RIS, and AM in patients out of a therapeutic drug monitoring (TDM) database complaining ADRs were categorized according to the Udvalg for Kliniske Undersogelser side effect rating scales (UKU) (n = 97) and compared to patients without ADRs (n = 398). RESULTS: Patients in the ADR group received a significantly lower daily dosage of risperidone (trimmed mean 3.64 mg/day) than patients without ADRs (4.40 mg/day). No differences were found for active moiety plasma concentrations between the groups (p = 0.454). Differences were detected only in the case of dose-adjusted plasma concentration values (concentration-by dose, C/D) for 9-OH-RIS, being higher in patients reporting ADRs (4.78 ng/mL/mg) than in patients without ADRs (4.3 ng/mL/mg) (p = 0.037 for Mann-Whitney U test). Note that differences for non-adjusted 9-OH-RIS plasma levels between groups failed to reach significance (p = 0.697). CONCLUSIONS: Our findings are consistent with previous data supporting a prominent role of 9 hydroxyrisperidone, but not of risperidone with regard to ADRs. When studying the various subgroups of reported ADRs separately, the size of these subsamples offers some plausible limitations by reducing the power of the analysis. PMID- 27376640 TI - Whole-genome sequencing in French Canadians from Quebec. AB - Genome-wide association studies (GWAS) have had a tremendous success in the identification of common DNA sequence variants associated with complex human diseases and traits. However, because of their design, GWAS are largely inappropriate to characterize the role of rare and low-frequency DNA variants on human phenotypic variation. Rarer genetic variation is geographically more restricted, supporting the need for local whole-genome sequencing (WGS) efforts to study these variants in specific populations. Here, we present the first large scale low-pass WGS of the French-Canadian population. Specifically, we sequenced at ~5.6* coverage the whole genome of 1970 French Canadians recruited by the Montreal Heart Institute Biobank and identified 29 million bi-allelic variants (31 % novel), including 19 million variants with a minor allele frequency (MAF) <0.5 %. Genotypes from the WGS data are highly concordant with genotypes obtained by exome array on the same individuals (99.8 %), even when restricting this analysis to rare variants (MAF <0.5, 99.9 %) or heterozygous sites (98.9 %). To further validate our data set, we showed that we can effectively use it to replicate several genetic associations with myocardial infarction risk and blood lipid levels. Furthermore, we analyze the utility of our WGS data set to generate a French-Canadian-specific imputation reference panel and to infer population structure in the Province of Quebec. Our results illustrate the value of low-pass WGS to study the genetics of human diseases in the founder French-Canadian population. PMID- 27376641 TI - MR image segmentation and bias field estimation based on coherent local intensity clustering with total variation regularization. AB - Though numerous segmentation algorithms have been proposed to segment brain tissue from magnetic resonance (MR) images, few of them consider combining the tissue segmentation and bias field correction into a unified framework while simultaneously removing the noise. In this paper, we present a new unified MR image segmentation algorithm whereby tissue segmentation, bias correction and noise reduction are integrated within the same energy model. Our method is presented by a total variation term introduced to the coherent local intensity clustering criterion function. To solve the nonconvex problem with respect to membership functions, we add auxiliary variables in the energy function such as Chambolle's fast dual projection method can be used and the optimal segmentation and bias field estimation can be achieved simultaneously throughout the reciprocal iteration. Experimental results show that the proposed method has a salient advantage over the other three baseline methods on either tissue segmentation or bias correction, and the noise is significantly reduced via its applications on highly noise-corrupted images. Moreover, benefiting from the fast convergence of the proposed solution, our method is less time-consuming and robust to parameter setting. PMID- 27376642 TI - [The third and new face of Chagas disease]. AB - After the publication of the results of the BENEFIT study concluding that the benznidazole (5 mg/kg/d/60 d) is ineffective to stop the progression of the established Chagas' cardiomyopathy in adults, the author evokes the new experiences and the new challenges of 2016 regarding Chagas disease while speculating on its future and by calling back some elements little known of his history, in particular the fact that it is Chagas who invented about it to some extent the concept of "neglected disease". PMID- 27376643 TI - Awareness and daily practices of family physicians and trainees towards laryngopharyngeal reflux. AB - Laryngopharyngeal reflux (LPR) is a type of reflux, seen with complaints of hoarseness, chronic cough, and globus sensation, different from gastroesophageal reflux disease (GERD). The aim of this study was to evaluate the awareness, knowledge, and practices of family physicians and trainees who were being trained in medical branches other than ENT and to determine the effective factors on decision making for diagnosis of this disorder. The study was designed as a two stage study. At the first stage, a data collection tool, involving 29 questions by which the knowledge, awareness, and applications of the physicians about LPR would be determined, was developed with 12 specialists, using Delphi method. At the second stage, 101 family physicians replied the questionnaire online. For 45 trainees other than ENT, the questionnaire was filled face-to-face by one of the investigators. In patients admitted with complaints of hoarseness, lasting longer than 2 weeks, cough, lasting longer than 3 weeks, and globus sensation, the physicians considered LPR as the preliminary diagnosis with rates of 88.4, 82.2, and 62.8 %, respectively. 87.0 % of physicians, participating in the study, started treatment for reflux empirically in patients having complaints of hoarseness, chronic cough, and globus sensation; however, only 29.0 % of physicians prescribed this treatment for periods of 3 or 6 months. 69.9 % of physicians, participating in the study, made a diagnosis of reflux in general during their daily practices; only 6.9 % made the discrimination between LPR and GERD. Of all physicians, 27.9 % prescribed double-dose PPI or H2. PMID- 27376644 TI - A 1842 skull from Dupuytren's museum of Paris: an original artifact of Joseph Gensoul first maxillectomy technique. AB - Joseph Gensoul was a pioneer of ENT surgery. In 1827, he performed the first total maxillectomy on 17-year-old boy. His work inspired many surgeons, who were previously unwilling to remove maxillary tumours. A paleopathological study performed in the Dupuytren museum allowed us to identify a skull from the early 19th century, with a large maxillar tumour. There were indications that this skull was operated according to Gensoul's technique. The aim of this study is to confirm that this patient had, in fact, received this surgical treatment. This is a historical and descriptive paleopathological study of a skull of the early 19th century of Dupuytren Museum in Paris. The historical research was conducted in collaboration with the French Academy of Medicine and the Museum of Medicine History (Paris). Bones mark cut studies allowed us to confirm that the patient was operated according to the method described by Gensoul in his "Surgical letter" in 1833. Our historical research has allowed us to understand the perspectives of surgeons in the 19th century and the intellectual processes that led to this discovery. At a time when the robotization and industrialization dominate our art, it is interesting to look to our past, our origins, and our history. The study of ancient humans remains and allows us to understand the origin of our specialty and pay tribute to these pioneering surgeons. Their intellectual approach and boldness should be acknowledged and applauded, especially as it is also the key to our success. PMID- 27376645 TI - Incidence and predictors of 30-day cardiovascular complications in patients undergoing head and neck cancer surgery. AB - Incidence and predictors of peri-operative or post-operative cardiovascular complications in head and neck cancer surgery remain poorly elucidated. In this retrospective study, we investigated the rate and pre-operative risk factors for cardiovascular and cerebrovascular complications. This study included all patients (n = 456) operated for head and neck cancer between 1999 and 2008. Patients' medical records were reviewed and the adjudication of endpoints was performed by adjudication committee. The 30-day incidence of cardiovascular and cerebrovascular complications was 7.2 %. Cardiac mortality at 30 days was 1.0 %. Univariate predictors of MACCE (major adverse cardiac and cerebrovascular events) at the 30-day follow-up were history of myocardial infarction (OR 4.56, 95 % CI 1.73-11.97, p = 0.002); history of heart failure (OR 4.14, 95 % CI 1.32-13.02, p = 0.015); pre-existing coronary artery disease (OR 3.98, 95 % CI 1.75-9.06, p = 0.001); prior aspirin medication (OR 3.73, 95 % CI 1.81-7.71, p < 0.001); prior betablocker medication (OR 3.67, 95 % CI 1.79-7.51, p < 0.001); hypertension (OR 2.55, 95 % CI 1.25-5.19, p = 0.010); and increasing age (OR 1.08, 95 % CI 1.05 1.12, p < 0.001). In a multivariate model, independent predictors of MACCE were pre-existing coronary artery disease (OR 2.45, 95 % CI 1.03-5.80, p = 0.042) and increasing age (OR 1.08, 95 % CI 1.04-1.11, p < 0.001). Patients having surgery for head and neck cancer are at high (>5 %) risk of developing vascular complications. Prior coronary artery disease and increasing age are independent risk factors for MACCE. PMID- 27376646 TI - Anti-adhesive effect of solid mixture of sodium hyaluronate/carboxymethylcellulose in murine nasal cavities. AB - The purpose of the study was to evaluate the effect of a solid mixture of sodium hyaluronate and carboxymethylcellulose (S-HA/CMC) for the prevention of adhesions after iatrogenic mucosal injury in murine nasal cavities. We introduced iatrogenic adhesions into the bilateral nasal cavities of 20 male Sprague-Dawley rats. S-HA/CMC was applied to the left nasal cavity, while no packing was placed in the right nasal cavity as a control. At 1, 2, and 4 weeks post-procedure, we examined the number of adhesions, the ratio of the longest cross-sectional length of adhesion to septal cartilage length (RAC), and the degree of fibrosis. S HA/CMC significantly reduced the number of adhesions when compared to the control group in total (p = 0.031), but not at each individual time point. The S-HA/CMC group showed significantly shorter RAC than the control group in total (p = 0.044), but not at each individual time point. The total fibrosis score was less severe in the S-HA/CMC group than in the control group (p < 0.001), with a significant difference between the two groups at the second week (p = 0.001). Therefore, in an animal model, S-HA/CMC can prevent post-injury mucosal adhesions suggesting a potential for clinical applications in endoscopic sinus surgery. Further clinical trials are needed to determine the safety and efficacy of S HA/CMC as nasal packing after endoscopic sinus surgery. PMID- 27376647 TI - Endovascular Management of Abdominal Aortic Aneurysms: the Year in Review. AB - OPINION STATEMENT: Endovascular aneurysm repair (EVAR) has become the predominant method of treatment for abdominal aortic aneurysms (AAA). The use of conscious sedation with local anesthesia and percutaneous femoral access has further decreased the morbidity of the procedure. Current devices can more effectively manage increasingly "hostile" aneurysm necks, while chimney grafts or dedicated fenestrated stent-grafts can be used for juxta-renal disease with favorable results. However, endovascular repair does present a new set of challenges, and endoleaks remain an area of concern. While there is general consensus that type I and type III endoleaks require treatment, type II endoleaks are the topic of ongoing research and debate. Development of devices and techniques to prevent and treat endoleak continues to progress. Advances in contrast-enhanced ultrasound are reducing reliance on computed tomography for post-operative monitoring. This is an important step in this population at high risk for the development of kidney failure. Despite these many innovations, further research is needed to optimize the care of patients with AAA. PMID- 27376649 TI - [Paratracheal lymph node with suspicion of carcinoma]. AB - Three paratracheal lymph nodes of a 20-year-old patient were submitted for examination, of which one showed numerous thyrocytes with large void nuclei and was suspected of being metastatic papillary thyroid carcinoma. The simultaneously resected thyroid gland, which was subsequently submitted showed findings consistent with Hashimoto's autoimmune thyroiditis (AIT). In the context of the resected goiter tissue, the suspected lymph node metastasis was identified as a hyperplastic ectopic (so-called parasitic) goiter nodule with thyrocytic changes typically seen in Hashimoto's AIT, such as oxyphilic cell alterations and a high plasma cell content. The re-examination of the suspicious lymph node revealed complete lack of a marginal sinus, thus excluding the diagnosis of a lymph node as well as the diagnosis of thyroid carcinoma metastasis. PMID- 27376648 TI - [HER2 testing in gastric cancer : Results of a meeting of German experts]. AB - Valid HER2 testing is essential for the optimal care of patients with HER2 positive gastric cancer and the correct use of first-line treatment. Although all cases of breast cancer are routinely tested for the HER2 status, HER2 testing in gastric cancer has still not become part of the routine and is usually only done upon request by the therapist. An interdisciplinary group of German experts has taken on the challenges of HER2 testing in gastric cancer as an opportunity to address essential aspects and questions on the practical use of HER2 testing in this indication from the perspective of pathologists and therapists. The recommendations made in this article reflect the consensus of all participants and correspond to their opinions and long-term experience. PMID- 27376651 TI - The association between characteristics of fathering in infancy and depressive symptoms in adolescence: A UK birth cohort study. AB - Evidence suggests that the quality of fathers' parenting has an impact on psychological outcomes during adolescence, but less is known about which aspects of fathering have the strongest effects. This study, using the Avon Longitudinal Study of Parents and Children (ALSPAC), considers which paternal attitudes towards and experiences of child care in infancy are most strongly associated with depressive symptoms in adolescence, and whether father effects are independent of maternal influence and other risk factors. Primary exposures were fathers' attitudes to and experiences of child care at 8 weeks, 8 months and 21 months coded as continuous scores; the primary outcome was self-reported depressive symptoms at 16 years (Short Moods and Feelings Questionnaire score >=11). Multivariable logistic regression models showed reasonably strong evidence that parental reports indicating potential paternal abuse when children were toddlers were associated with a 22% increased odds of depressive symptoms at age 16 (odds ratio [OR] 1.22 [95% CI 1.11, 1.34] per SD). There was some evidence for an interaction with social class (p=0.04): for children living in higher social class households (professional, managerial and technical classes), an increase in the potential abuse scale increased the odds of depressive symptoms by 31% (OR 1.31 [1.13, 1.53] per SD), whereas there was no effect in the lower social class categories. The potential paternal abuse measure needs to be validated and research is needed on what circumstances predict anger and frustration with child care. Effective interventions are needed to help fathers cope better with parenting stress. PMID- 27376650 TI - The role of oncostatin M regulates osteoblastic differentiation of dental pulp stem cells through STAT3 pathway. AB - Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells, which have the self-renewal and multi-lineage differentiation potential, including chondrocytes, adipocytes, neural cells and osteoblasts. So they play a significant role in pulp repair and bone regeneration. Oncostatin M (OSM), one of the IL-6 family cytokines, inhibits adipogenic differentiation and stimulates osteogenic differentiation of human bone marrow mesenchymal stem cells. However, the effect of OSM on DPSCs is unclear. We found that OSM induced osteogenic differentiation of DPSCs, promoting matrix mineralization as measured by Alizarin Red S staining. OSM also increased expression of osteogenesis-associated gene products Alkaline phosphatase, Bone morphogenetic protein 2 (BMP2), Runt-related transcription factor 2 and Osteocalcin (OCN) as assessed by immunoblotting. We also found that OSM activated the Signal Transducer And Activator Of Transcription 3 (STAT3) pathway during the osteogenic differentiation of DPSCs. Blocking the osteogenic differentiation by silencing of STAT3 can significantly inhibit OSM-induced osteogenic differentiation of DPSCs and the expression of related genes, furthermore matrix mineralization was also suppressed. In summary, OSM promotes osteoblastic differentiation of DPSCs and osteogenesis-related genes expression through the JAK3/STAT3 signaling pathway which may be useful for the autologous transplantation of DPSCs. PMID- 27376652 TI - School bus travel is associated with bullying victimization among Canadian male, but not female, middle and high school students. AB - Previous research has found a link between active school transportation and bullying victimization among school-aged children. However, the link with other school travel modes (such as car, school bus, and public transportation) and bullying victimization is largely unknown. The purpose of this study was to investigate the association between school travel mode and report of bullying victimization among Canadian middle and high school students. The sample consisted of 5065 students aged 11-20 years (mean age: 15.2+/-1.9 years; 56% females) who participated in the 2013 Ontario Students Drug Use and Health Survey (OSDUHS). Overall, 24.7% of students reported school bullying victimization in the past year. Females (27.2%) were more likely than males (22.3%) to be victims of school bullying (p<0.01). After adjustment for age, ethnicity, subjective socioeconomic status and parental education, multivariable logistic regression analyses indicated that, compared to active school transportation, school bus travel to (adjusted odd ratio (OR)=1.83; 95% confidence interval (CI)=1.25-2.68) and from (OR=1.79; 95% CI=1.70-2.67) school was associated with greater odds of bullying victimization among males, but not females. However, the use of public transportation to get to school was associated with lower odds of bullying victimization compared to active transportation among females only (OR=0.59; 95% CI=0.36-0.97). These findings suggest that school travel mode should be considered when considering risks for bullying victimization. Bullying prevention efforts should target school buses to make children's commute a safe and enjoyable experience. PMID- 27376653 TI - Drug interactions between antiretrovirals and drugs used to treat benign prostatic hyperplasia/lower urinary tract symptoms. AB - INTRODUCTION: Significant advances in antiretroviral (ARV) therapy have transformed HIV into a chronic manageable disease. Co-morbidities associated with aging, such as benign prostatic hyperplasia (BPH), are becoming increasingly prevalent in the HIV-infected population. The pharmacological treatment of BPH involves medications mainly metabolized by CYP 450 enzymes, while many ARVs have inducing or inhibiting effects on the CYP 450 system. Consequently, there is potential for significant pharmacokinetic (PK) interactions between these two classes of medications. AREAS COVERED: This article reviews the pharmacology and metabolism of selected BPH drug therapies and ARVs, in addition to highlighting potential interactions between these two drug categories. The authors also present PK evidence of interactions from available clinical trials, product monographs and international conference abstracts. Potentially significant drug interactions are summarized and strategies for management are discussed. EXPERT OPINION: Drugs most likely to interact with BPH medications include protease inhibitors, the non-nucleoside reverse transcriptase inhibitors efavirenz, nevirapine, etravirine, and the cobicistat-boosted integrase inhibitor elvitegravir. Clinically significant PK interactions with BPH medications and dolutegravir, raltegravir, rilpivirine, or the investigational agent doravirine do not appear to exist. Clinicians working with HIV-infected individuals need to recognize the potential for interactions involving BPH and ARV treatments to ensure effective and safe drug therapy use. PMID- 27376654 TI - A long survivor with local relapse of hilar cholangiocarcinoma after R1 surgery treated with chemoradiotherapy: a case report and literature review. AB - The treatment outcome of extrahepatic cholangiocarcinoma remains insufficient because it is difficult to obtain accurate diagnosis of tumor spreading and effective treatment agent is quite limited in spite of substantial current efforts, all of which have been unsuccessful except for gemcitabine plus cisplatin. The patient was a 60-year-old female who had developed hilar cholangiocarcinoma and underwent extrahepatic bile duct resection. Although it was conceivable that it would be the R1 resection, the patient wanted to receive limited resection to avoid postoperative complication mainly because she was depressed. In histology, interstitial spreading of tumor was appreciated at the surgical margin of bile duct. The patient did not accept to receive the additional treatment after the surgery and hardly visited the hospital to take the periodical test for monitoring the residual cancer cells. As expected, the local relapse of tumor was appreciated 1 year after the R1 surgery. She chose radiotherapy and agreed with subsequent S-1 treatment for 26 months. Consequently, elevated CA19-9 was decreased, and local relapse has been successfully controlled for more than 7 years after the relapse of tumor. Here, we report quite a rare case in terms of long survivor after chemoradiotherapy on locally relapsed unresectable hilar cholangiocarcinoma. PMID- 27376655 TI - [Analysis of contemporary hospital infrastructure pertaining to infection prevention in Germany]. AB - BACKGROUND: A high percentage of single-bed rooms and antiseptic hand rub dispensers in hospitals are required for infection prevention OBJECTIVE: Data acquisition of the hospitals' current status of infrastructure pertaining to infection prevention MATERIALS AND METHODS: A electronic questionnaire was sent in March 2015 to all hospitals participating in the nosocomial infection surveillance system (KISS) to collect operational infrastructure data. RESULTS: Completed questionnaires were received from 621 hospitals (response rate 46 %) and provided data about the building infrastructure of 534 intensive care units and 621 representative medical wards. While most beds in the intensive care unit are equipped with an antiseptic hand rub dispenser at the bedside, only 31.5 % of the medical ward beds are so equipped. Moreover, only 27.1 % of intensive care beds and 6.4 % of medical ward beds are in single-bed rooms. The intensive care room size showed a median of 18 m2 for single-bed rooms and 28 m2 for two-bed rooms. In the medical wards, 28.2 % of the patient rooms are not equipped with an ensuite toilet. CONCLUSIONS: The paucity of bedside antiseptic hand rub dispensers in medical wards should be rectified at once to optimize hand hygiene compliance of health care workers. Likewise, the lack of single-bed rooms on medical wards and intensive care units should be considered when renovating old or planning new buildings in the near future. PMID- 27376656 TI - The interactive role of income (material position) and income rank (psychosocial position) in psychological distress: a 9-year longitudinal study of 30,000 UK parents. AB - PURPOSE: Parents face an increased risk of psychological distress compared with adults without children, and families with children also have lower average household incomes. Past research suggests that absolute income (material position) and income status (psychosocial position) influence psychological distress, but their combined effects on changes in psychological distress have not been examined. Whether absolute income interacts with income status to influence psychological distress are also key questions. METHODS: We used fixed effects panel models to examine longitudinal associations between psychological distress (measured on the Kessler scale) and absolute income, distance from the regional mean income, and regional income rank (a proxy for status) using data from 29,107 parents included in the UK Millennium Cohort Study (2003-2012). RESULTS: Psychological distress was determined by an interaction between absolute income and income rank: higher absolute income was associated with lower psychological distress across the income spectrum, while the benefits of higher income rank were evident only in the highest income parents. Parents' psychological distress was, therefore, determined by a combination of income related material and psychosocial factors. CONCLUSIONS: Both material and psychosocial factors contribute to well-being. Higher absolute incomes were associated with lower psychological distress across the income spectrum, demonstrating the importance of material factors. Conversely, income status was associated with psychological distress only at higher absolute incomes, suggesting that psychosocial factors are more relevant to distress in more advantaged, higher income parents. Clinical interventions could, therefore, consider both the material and psychosocial impacts of income on psychological distress. PMID- 27376657 TI - Maternal psychopathology and offspring clinical outcome: a four-year follow-up of boys with ADHD. AB - Previous cross-sectional research has shown that parents of children with attention deficit hyperactivity disorder (ADHD) have high rates of psychopathology, especially ADHD and depression. However, it is not clear whether different types of parent psychopathology contribute to the course and persistence of ADHD in the child over time. The aim of this two wave study was to investigate if mother self-reported ADHD and depression influence persistence of offspring ADHD and conduct disorder symptom severity in adolescents diagnosed with ADHD in childhood. A sample of 143 males with a confirmed diagnosis of ADHD participated in this study. ADHD and conduct disorder symptoms were assessed at baseline and reassessed 4 years later. The boys in this sample had a mean age of 10.7 years at Time 1 (SD 2.14, range 6-15 years) and 13.73 years at Time 2 (SD 1.74, range 10-17 years). Questionnaire measures were used to assess ADHD and depression symptoms in mothers at Time 1. Mother self-reported ADHD was not associated with a change in child ADHD or conduct symptom severity over time. Mother self-reported depression was found to predict an increase in child conduct disorder symptoms, but did not contribute to ADHD symptom levels. This study provides the first evidence that concurrent depression in mothers may be a predictor of worsening conduct disorder symptoms in adolescents with ADHD. It may, therefore, be important to screen for depression in mothers of children with ADHD in clinical practice to tailor interventions accordingly. PMID- 27376659 TI - Limits on lexical prediction during reading. AB - Efficient language processing may involve generating expectations about upcoming input. To investigate the extent to which prediction might facilitate reading, a large-scale survey provided cloze scores for all 2689 words in 55 different text passages. Highly predictable words were quite rare (5% of content words), and most words had a more-expected competitor. An eye-tracking study showed sensitivity to cloze probability but no mis-prediction cost. Instead, the presence of a more-expected competitor was found to be facilitative in several measures. Further, semantic and morphosyntactic information was highly predictable even when word identity was not, and this information facilitated reading above and beyond the predictability of the full word form. The results are consistent with graded prediction but inconsistent with full lexical prediction. Implications for theories of prediction in language comprehension are discussed. PMID- 27376658 TI - Investigating the effects of tropomyosin mutations on its flexibility and interactions with filamentous actin using molecular dynamics simulation. AB - Tropomyosin (Tpm) is a two-chained alpha-helical coiled-coil protein that binds to filamentous actin (F-actin), and regulates its interactions with myosin by occupying three average positions on F-actin (blocked, closed, and open). Mutations in the Tpm are linked to heart diseases including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). To elucidate the molecular mechanisms of Tpm mutations (including DCM mutation E54K, HCM mutations E62Q, A63V, K70T, V95A, D175N, E180G, L185R, E192K, and a designed synthetic mutation D137L) in terms of their effects on Tpm flexibility and its interactions with F actin, we conducted extensive molecular dynamics simulations for the wild-type and mutant Tpm in complex with F-actin (total simulation time 160 ns per mutant). The mutants exhibited distinct changes (i.e., increase or decrease) in the overall and local flexibility of the Tpm coiled-coil, with each mutation causing both local and long-range modifications of the Tpm flexibility. In addition, our binding calculations revealed weakened Tpm-F-actin interactions (except for L185R, D137L and A63V) involving five periods of Tpm, which correlate with elevated fluctuation of Tpm relative to the blocked position on F-actin that may lead to easier activation and increased Ca2+-sensitivity. We also simulated the alphabeta/betaalpha-Tpm heterodimer in comparison with the alphaalpha-Tpm homodimer, which revealed greater flexibility and weaker actin binding in the heterodimer. Our findings are consistent with a complex mechanism underlying how different Tpm mutations perturb the Tpm function in distinct ways (e.g., by affecting specific sites of Tpm), which bear no simple links to the disease phenotypes (e.g., HCM vs. DCM). PMID- 27376660 TI - Risk and protective factors for antepartum and postpartum depression: a prospective study. AB - INTRODUCTION: Antepartum risk and protective factors for postpartum depression (PPD; the most common mental disorder after childbirth besides postpartum anxiety), have been frequently investigated in cross-sectional studies, but less often longitudinally. This study examined linear and moderator effects of risk and protective factors for peripartum depression. First, we investigated the predictive power of risk factors (physical problems during pregnancy, pregnancy related anxiety, stressful life events, dysfunctional self-consciousness (DSC)) and protective factors (resilience, social support) for antepartum depression (APD) and PPD. Second, as DSC plays an important role in major depression, we examined whether the protective factors moderate the association between the risk factors DSC and APD as well as PPD. METHODS: We conducted a prospective study with three measurement time points: six weeks antepartum (N = 297), as well as six weeks (N = 278) and twelve weeks (N = 266) postpartum. Direct and moderator effects on APD were analyzed using hierarchical regression analysis. Moderated mediation effects were investigated to explore whether the indirect, long-term effect of DSC on PPD six weeks after birth (PPD-6) and PPD twelve weeks after birth (PPD-12) is moderated by resilience. RESULTS: Predictors for APD were high DSC, high concerns about one's appearance, low resilience and low social support. Resilience buffered (weakened) the impact of DSC on APD and affected PPD-6 and PPD-12 indirectly through APD. DISCUSSION: The results suggest that PPD-12 is influenced directly and indirectly through PPD-6 by APD, but that this effect depends upon risk and protective factors, especially on the combined effects of resilience and DSC. The key finding of our study is the moderating (i.e. weakening) effect of resilience on the relationship between DSC and depression. Resilience and DSC may be an important issue for depression prevention and treatment programs in the peripartum period. PMID- 27376661 TI - Influence of Statin Pretreatment on Initial Neurological Severity and Short-Term Functional Outcome in Acute Ischemic Stroke Patients: The Fukuoka Stroke Registry. AB - BACKGROUND: Statins have neuroprotective effects against ischemic stroke. However, associations between pre-stroke statin treatment and initial stroke severity and between the treatment and functional outcome remain controversial. This study aimed at determining these associations in ischemic stroke patients. METHODS: Among patients registered in the Fukuoka Stroke Registry from June 2007 to October 2014, 3,848 patients with ischemic stroke within 24 h of onset, who had been functionally independent before onset, were enrolled in this study. Ischemic stroke was classified as cardioembolic or non-cardioembolic infarction. Primary and secondary study outcomes were mild neurological symptoms defined as a National Institutes of Health Stroke Scale score of <=4 on admission and favorable functional outcome defined as a modified Rankin Scale score of <=2 at discharge, respectively. Multivariable logistic regression models were used to quantify associations between pre-stroke statin treatment and study outcomes. RESULTS: Of all 3,848 participants, 697 (18.1%) were taking statins prior to the stroke. The frequency of mild neurological symptoms was significantly higher in patients with pre-stroke statin treatment (64.1%) than in those without the treatment (58.3%, p < 0.01). Multivariable analysis showed that pre-stroke statin treatment was significantly associated with mild neurological symptoms (OR 1.31; 95% CI 1.04-1.65; p < 0.01). Sensitivity analysis in patients with dyslipidemia (n = 1,998) also showed the same trend between pre-stroke statin treatment and mild neurological symptoms (multivariable-adjusted OR 1.26; 95% CI 0.99-1.62; p = 0.06). In contrast, the frequency of favorable functional outcome was not different between patients with (67.0%) and without (65.3%) the treatment (p = 0.40). Multivariable analysis also showed no significant association between pre stroke statin treatment and favorable functional outcome (OR 1.21; 95% CI 0.91 1.60; p = 0.19). Continuation of statin treatment, however, was significantly associated with favorable functional outcome among patients with pre-stroke statin treatment (multivariable-adjusted OR 2.17; 95% CI 1.16-4.00; p = 0.02). CONCLUSIONS: Pre-stroke statin treatment in ischemic stroke patients was significantly associated with mild neurological symptoms within 24 h of onset. Pre-stroke statin treatment per se did not significantly influence the short-term functional outcome; however, continuation of statin treatment during the acute stage of stroke seems to relate with favorable functional outcome for patients with pre-stroke statin treatment. PMID- 27376662 TI - Memory as embodiment: The case of modality and serial short-term memory. AB - Classical explanations for the modality effect-superior short-term serial recall of auditory compared to visual sequences-typically recur to privileged processing of information derived from auditory sources. Here we critically appraise such accounts, and re-evaluate the nature of the canonical empirical phenomena that have motivated them. Three experiments show that the standard account of modality in memory is untenable, since auditory superiority in recency is often accompanied by visual superiority in mid-list serial positions. We explain this simultaneous auditory and visual superiority by reference to the way in which perceptual objects are formed in the two modalities and how those objects are mapped to speech motor forms to support sequence maintenance and reproduction. Specifically, stronger obligatory object formation operating in the standard auditory form of sequence presentation compared to that for visual sequences leads both to enhanced addressability of information at the object boundaries and reduced addressability for that in the interior. Because standard visual presentation does not lead to such object formation, such sequences do not show the boundary advantage observed for auditory presentation, but neither do they suffer loss of addressability associated with object information, thereby affording more ready mapping of that information into a rehearsal cohort to support recall. We show that a range of factors that impede this perceptual-motor mapping eliminate visual superiority while leaving auditory superiority unaffected. We make a general case for viewing short-term memory as an embodied, perceptual-motor process. PMID- 27376663 TI - Accumulation of neurotoxic organochlorines and trace elements in brain of female European eel (Anguilla anguilla). AB - Xenobiotics such as organochlorine compounds (OCs) and metals have been suggested to play a significant role in the collapse of European eel stocks in the last decades. Several of these pollutants could affect functioning of the nervous system. Still, no information is so far available on levels of potentially neurotoxic pollutants in eel brain. In present study, carried out on female eels caught in Belgian rivers and canals, we analyzed brain levels of potentially neurotoxic trace elements (Ag, Al, As, Cd, Co, Cr, Cu, Fe, Hg, MeHg, Mn, Ni, Pb, Sn, Sb, Zn) and OCs (Polychlorinated biphenyls, PCBs; Hexachlorocyclohexanes, HCHs; Dichlorodiphenyltrichloroethane and its metabolites, DDTs). Data were compared to levels in liver and muscle tissues. Eel brain contained very high amounts of OCs, superior to those found in the two other tissues. Interestingly, the relative abundance of PCB congeners markedly differed between tissues. In brain, a predominance of low chlorinated PCBs was noted, whereas highly chlorinated congeners prevailed in muscle and liver. HCHs were particularly abundant in brain, which contains the highest amounts of beta-HCH and Upsilon HCH. p,p'-DDTs concentration was similar between brain and muscle (i.e., about twice that of liver). A higher proportion of p,p'-DDT was noticed in brain. Except for Cr and inorganic Hg, all potentially neurotoxic metals accumulated in brain to levels equal to or lower than hepatic levels. Altogether, results indicate that eel brain is an important target for organic and, to a lesser extent, for inorganic neurotoxic pollutants. PMID- 27376664 TI - Comparison of beta-lactam plus aminoglycoside versus beta-lactam plus fluoroquinolone empirical therapy in serious nosocomial infections due to Gram negative bacilli. AB - We sought to compare clinical cure on day 7 and a 28-day all-cause mortality in patients who received an anti-pseudomonal beta-lactam with a fluoroquinolone or an aminoglycoside for treatment of nosocomial bacteremia or pneumonia due to Gram negative bacilli while in the ICU. This retrospective cohort study was conducted in critically ill patients at an academic medical centre from January 2005 to August 2011. A total of 129 patients (83 receiving aminoglycoside and 46 receiving fluoroquinolone combinations) were included. Seven-day clinical cure rates were 74% and 72% for fluoroquinolone and aminoglycoside groups, respectively (p = 0.84). There was no significant difference in the odds of clinical cure with a fluoroquinolone as compared to an aminoglycoside combination (adjusted odds ratio 2.4, 95% confidence interval [CI] 0.7-9.0). There was no significant difference in 28-day mortality in patients who received a fluoroquinolone or an aminoglycoside combination (22% vs. 18%, adjusted hazard ratio 0.82, 95% CI 0.29-2.28). PMID- 27376666 TI - Prevalence and correlates of psychotic experiences amongst children of depressed parents. AB - Psychotic experiences in young people are substantially more common than psychotic disorders, and are associated with distress and functional impairment. Family history of depression as well as of schizophrenia increases risk for psychotic experiences, but the prevalence of such experiences and their clinical relevance in offspring of depressed parents is unknown. Our objectives were to explore i) the prevalence of psychotic experiences amongst offspring of parents with recurrent unipolar depression and ii) the relationship between psychotic experiences and other psychopathology. Data were drawn from the 'Early Prediction of Adolescent Depression' longitudinal study of high-risk offspring (aged 9-17 years at baseline) of 337 parents with recurrent depression. Three assessments were conducted over four years. Psychopathology was assessed using the Child and Adolescent Psychiatric Assessment. Seventy-eight percent of families (n=262) had complete data on psychotic experiences at each of the three time points. During the study, 8.4% (n=22; 95% CI 5.0%, 11.8%) of offspring reported psychotic experiences on at least one occasion, and these were associated with psychiatric disorder, specifically mood and disruptive disorders, and suicidal thoughts/behaviour. Psychotic experiences amongst offspring of depressed parents index a range of psychopathology. Further research is needed to examine their clinical significance and long-term consequences. PMID- 27376667 TI - Prevalence of depression and its associated factors among Chinese elderly people: A comparison study between community-based population and hospitalized population. AB - Depression is common among elderly people, but people from various study settings were at different levels of risk for depression. However, most of the existing studies were conducted among community population, and little was known about depression among institutionalized population. In this study, using a national sample, we aimed to compare the prevalence rate of depression and its associated factors between community-dwelling elderly people (CDEP) and elderly medical inpatients (EMI). Data for this study was derived from a national survey of the 2011 Comprehensive Assessment of Elderly Health. The Geriatric Depression Scale was used to assess depression. The results indicated that the prevalence rate of depression among EMI was significantly higher than that in CDEP (18.1% vs 11.6%, P<0.001). Physical health status was found to be the most important factor associated with depression among both groups. This study revealed a high prevalence rate of depression among Chinese elderly people, especially for those medically institutionalized. It's essential to pay more efforts on the training of general practitioners for early screening and identification of depression on the admission of elderly patients and during their hospitalization, and case management of the elderly medical inpatients on assessment and treatment for depression may be beneficial. PMID- 27376665 TI - Engineering membrane and cell-wall programs for tolerance to toxic chemicals: Beyond solo genes. AB - Metabolite toxicity in microbes, particularly at the membrane, remains a bottleneck in the production of fuels and chemicals. Under chemical stress, native adaptation mechanisms combat hyper-fluidization by modifying the phospholipids in the membrane. Recent work in fluxomics reveals the mechanism of how membrane damage negatively affects energy metabolism while lipidomic and transcriptomic analyses show that strains evolved to be tolerant maintain membrane fluidity under stress through a variety of mechanisms such as incorporation of cyclopropanated fatty acids, trans-unsaturated fatty acids, and upregulation of cell wall biosynthesis genes. Engineered strains with modifications made in the biosynthesis of fatty acids, peptidoglycan, and lipopolysaccharide have shown increased tolerance to exogenous stress as well as increased production of desired metabolites of industrial importance. We review recent advances in elucidation of mechanisms or toxicity and tolerance as well as efforts to engineer the bacterial membrane and cell wall. PMID- 27376668 TI - The psychometric properties of the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) and the Patient Health Questionnaire-9 (PHQ-9) in depressed inpatients in China. AB - This study examined the psychometric properties of the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) and Patient Health Questionnaire 9 (PHQ-9). The study sample comprised 297 depressed inpatients. The severity of depressive symptoms was assessed with the Hamilton Rating Scale for Depression, the QIDS-SR and the PHQ-9 in all subjects at baseline and a random sample of 50 subjects two weeks later. The internal consistency, convergent validity, factor structure and sensitivity to change of these scales were assessed. Internal consistency (Cronbach's alpha) of the PHQ-9 and QIDS-SR were 0.88 and 0.83, respectively at baseline and 0.91 and 0.87, respectively at exit. Item to total score correlations were higher for the PHQ-9 than those for the QIDS-SR at baseline and exit. Three domains at baseline and two at study exit of the QIDS-SR had a correlation less than 0.65; while only two items at baseline and no item at exit were less than 0.65 for the PHQ-9. Both the PHQ-9 and the QIDS-SR showed uni dimensional measurement properties at baseline; the two instruments were less sensitive than the HAMD to detect changes of depressive symptoms suggesting low convergent validity. The QIDS-SR and the PHQ-9 have similar and acceptable psychometric properties in most domains as tested in depressed inpatients. PMID- 27376669 TI - A 12-Month prospective study of the effects of PTSD-depression comorbidity on suicidal behavior in Iraq/Afghanistan-era veterans. AB - The present study used validated clinical interviews to assess the effect of comorbid PTSD-depression on suicidal behavior over the course of 12 months in 309 Iraq/Afghanistan-era veterans. Logistic regression models demonstrated that comorbid PTSD-depression was a statistically significant predictor of suicide attempts at the 12-month follow-up in both the total sample and in the subset of veterans with PTSD/depression (n=98). In contrast, gender, age, race, sexual orientation, and baseline history of suicide attempts did not have significant effects. These findings suggest that comorbid PTSD-depression may be a significant risk factor for future suicidal behavior in veterans. PMID- 27376670 TI - Causal beliefs about intellectual disability and schizophrenia and their relationship with awareness of the condition and social distance. AB - Evidence on mental illness stigma abounds yet little is known about public perceptions of intellectual disability. This study examined causal beliefs about intellectual disability and schizophrenia and how these relate to awareness of the condition and social distance. UK lay people aged 16+(N=1752), in response to vignettes depicting intellectual disability and schizophrenia, noted their interpretation of the difficulties, and rated their agreement with 22 causal and four social distance items. They were most likely to endorse environmental causes for intellectual disability, and biomedical factors, trauma and early disadvantage for schizophrenia. Accurate identification of both vignettes was associated with stronger endorsement of biomedical causes, alongside weaker endorsement of adversity, environmental and supernatural causes. Biomedical causal beliefs and social distance were negatively correlated for intellectual disability, but not for schizophrenia. Causal beliefs mediated the relationship between identification of the condition and social distance for both conditions. While all four types of causal beliefs acted as mediators for intellectual disability, for schizophrenia only supernatural causal beliefs did. Educating the public and promoting certain causal beliefs may be of benefit in tackling intellectual disability stigma, but for schizophrenia, other than tackling supernatural attributions, may be of little benefit in reducing stigma. PMID- 27376671 TI - The similarities and differences in impulsivity and cognitive ability among ketamine, methadone, and non-drug users. AB - The study aimed to identify similarities and differences among ketamine, methadone users, and non-drug-using controls, on impulsivity, antisocial personality, and related cognitive abilities. A case-control observational design was used to compare the impulsivity and cognitive function of ketamine users (n = 51), methadone users (n=59), and controls (n=60). Antisocial personality traits and emotion states were also measured. One-way ANOVAs and planned post hoc pair wise tests were used to analyze the data. Compared to non-drug-using controls, ketamine and methadone users had elevated scores on BIS and Pd scale of the MMPI, poorer performance on 2-back task, Stop-signal task, and Stroop test. Ketamine users performed the worst in the 2-back accuracy and Stop miss rate compared to methadone users and controls. There were no significant differences between the groups on the Iowa Gambling Task. Ketamine users did not show deficits in decision-making but exhibited strong impulsivity, antisocial personality, and poor response inhibition and working memory at levels similar to methadone users. These deficits may reflect vulnerability to addiction. This suggests that future treatment programs for ketamine users could address drug users' impulsive cognition and psychopathic deviance. PMID- 27376672 TI - SV40 T-Antigen Amino Acid Changes that Disrupt Cul-7 or Bub-1 Binding Do Not Globally Distort the T-Common Region. AB - BACKGROUND: Amino acids 1-107 of the SV40 T antigen constitute a functionally important and complex region. Cellular proteins, Hsc70, Bub-1, Cul-7, and Rb, each of which is involved in cell growth control or genomic stability, bind within this portion of the T antigen. Mutational analysis has mapped the J domain/Hsc70, Bub-1, and the Rb binding motifs. Two regions of the T antigen have been implicated in Cul-7 binding. Mutation of F98A diminished Cul-7 binding, and deletion of amino acids 68-83 abolished it. The authors suggest, based on T antigen structure, that F98 is inaccessible and that the F98A change altered the configuration of the upstream region, preventing Cul-7 binding. Our objective was to determine, by using monoclonal T-antigen antibodies, whether F98 is accessible and whether F98A substitution globally distorted the T-common region. METHODS: Cell-expressing T antigens, immunoprecipitation, and immunoblot were used to determine the accessibility of amino acids. CONCLUSION: Full-length T-antigen and N-terminal fragments containing F98A were immunoprecipitated by monoclonal antibody PAb902, which recognizes a conformation-dependent epitope within the first 82 amino acids. Therefore, this alteration does not globally distort the entire T-common region. Additionally, PAb416, which displaces Cul-7 from the T antigen and immunoprecipitates bound pRb peptides, depends on F98 for binding, implying that amino acid 98 is part of the epitope and accessible in the native T antigen. PMID- 27376673 TI - How Octogenarians with Bladder Cancer Are Treated in a Maximum-Care Hospital: The Real-Life Experience. AB - INTRODUCTION: With increasing life expectancy, curative treatment of octogenarians with urothelial carcinoma of the bladder (UCB) becomes more important. MATERIALS AND METHODS: The treatment modalities of 276 octogenarians with UCB who were treated at the University Hospital of Erlangen between 1982 and 2011 were assessed retrospectively. RESULTS: One hundred forty-six patients had non-muscle invasive bladder cancer (NMIBC) while 71 had muscle invasive bladder cancer (MIBC). No data was available for 59 patients. Eighty-five (58.2%) of the 146 patients with NMIBC received transurethral resection of the bladder tumor (TURBT) only, another 38 patients (26%) underwent additional intravesical therapy; and 8.9% were treated with radiochemotherapy (RCT), 4.1% with radiotherapy (RT), 1.4% with systemic chemotherapy and 1.4% with radical cystectomy (RC). Of the 71 patients suffering from MIBC, 39 (54.9%) received TURBT alone. A potentially curative therapy was performed on 31 of the 71 patients with MIBC (43.7%). Of these, 16 patients (51.6%) received RCT, 9 patients (29.0%) RT and 6 patients (19.4%) RC. In Kaplan-Meier analysis, patients with MIBC had better median overall survival with curative treatment compared to TURBT alone (28 vs. 9 months; p < 0.001, log-rank test). CONCLUSIONS: By offering a wide range of treatment options, over 43% of octogenarians with MIBC received a curative therapy at a maximum care hospital. PMID- 27376674 TI - Knockdown of strigolactone biosynthesis genes in Populus affects BRANCHED1 expression and shoot architecture. AB - Plant architecture is modified by a regulatory system that controls axillary bud outgrowth. Key components in this system are strigolactones (SLs) and BRANCHED1, which inhibit bud outgrowth. Their role has been described in herbaceous model systems, including Arabidopsis, rice and pea. However, a role in woody perennial species, including the model tree poplar, has not been unequivocally proven. In this study, we tested a role for SLs in Populus * canescens by treatment with the synthetic SL GR24. We generated MORE AXILLARY BRANCHING4 (MAX4) knockdown lines to study the architectural phenotype of poplar SL biosynthesis mutants and the expression of SL-regulated genes. We show that GR24 is perceived by the model tree poplar. MAX4 knockdown lines exhibit typical SL deficiency symptoms. The observed changes in branching pattern, internode length and plant height can be rescued by grafting. We identified putative poplar BRANCHED1 and BRANCHED2 genes and provide evidence for a regulation of BRANCHED1 by SLs. Our results suggest a conservation of major regulatory mechanisms in bud outgrowth control in the model tree poplar. This may facilitate further research, pinpointing the role of SLs and BRANCHED1 in the complex regulation of bud outgrowth in trees. PMID- 27376676 TI - Efficient Low-Temperature Solution-Processed Lead-Free Perovskite Infrared Light Emitting Diodes. AB - Lead-free perovskite infrared light-emitting diodes are achieved by using a halide perovskite CsSnI3 as an emissive layer. The film shows compact micrometer sized grains with only a few pinholes and cracks at the grain boundaries. The device exhibits maximum radiance of 40 W sr-1 m-2 at a current density of 364.3 mA cm-2 and maximum external quantum efficiency of 3.8% at 4.5 V. PMID- 27376675 TI - RNA-based therapies for genodermatoses. AB - Genetic disorders affecting the skin, genodermatoses, constitute a large and heterogeneous group of diseases, for which treatment is generally limited to management of symptoms. RNA-based therapies are emerging as a powerful tool to treat genodermatoses. In this review, we discuss in detail RNA splicing modulation by antisense oligonucleotides and RNA trans-splicing, transcript replacement and genome editing by in vitro-transcribed mRNAs, and gene knockdown by small interfering RNA and antisense oligonucleotides. We present the current state of these therapeutic approaches and critically discuss their opportunities, limitations and the challenges that remain to be solved. The aim of this review was to set the stage for the development of new and better therapies to improve the lives of patients and families affected by a genodermatosis. PMID- 27376677 TI - A polyphasic approach for characterization of a collection of cereal isolates of the Fusarium incarnatum-equiseti species complex. AB - DNA-based phylogenetic analyses have resolved the fungal genus Fusarium into multiple species complexes. The F. incarnatum-equiseti species complex (FIESC) includes fusaria associated with several diseases of agriculturally important crops, including cereals. Although members of FIESC are considered to be only moderately aggressive, they are able to produce a diversity of mycotoxins, including trichothecenes, which can accumulate to harmful levels in cereals. High levels of cryptic speciation have been detected within the FIESC. As a result, it is often necessary to use approaches other than morphological characterization to distinguish species. In the current study, we used a polyphasic approach to characterize a collection of 69 FIESC isolates recovered from cereals in Europe, Turkey, and North America. In a species phylogeny inferred from nucleotide sequences from four housekeeping genes, 65 of the isolates were resolved within the Equiseti clade of the FIESC, and four isolates were resolved within the Incarnatum clade. Seven isolates were resolved as a genealogically exclusive lineage, designated here as FIESC 31. Phylogenies based on nucleotide sequences of trichothecene biosynthetic genes and MALDI-TOF MS (Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry) were largely concordant with phylogeny inferred from the housekeeping gene. Finally, Liquid Chromatography (Time-Of-Flight) Mass Spectrometry [LC-(TOF-)MS(/MS)] revealed variability in mycotoxin production profiles among the different phylogenetic species investigated in this study. PMID- 27376678 TI - Survival and growth of Listeria monocytogenes on whole cantaloupes is dependent on site of contamination and storage temperature. AB - Whole cantaloupes (Cucumis melo L.), marketed as 'Rocky Ford', were implicated in a large multi-state outbreak of listeriosis in the United States in 2011; however, survival and growth of Listeria monocytogenes on whole cantaloupes remains relatively unexplored. The research presented here evaluated three different storage temperatures, two sites of contamination of cantaloupes, and two cantaloupe varieties to determine their effect on the survival of L. monocytogenes. 'Athena' and 'Rocky Ford' cantaloupe cultivars were grown in soil and harvested, and individual melons subsequently received a multi-strain inoculum of L. monocytogenes (6 log CFU/melon), which were then stored at 4 degrees C, 10 degrees C, and 25 degrees C. Changes in L. monocytogenes populations on the rinds and stem scars of cantaloupes stored at each temperature were determined at selected times for up to 15days. An analysis of variance revealed that inoculation site and storage temperature significantly affected survival of L. monocytogenes on cantaloupes during storage (p<0.05), but cultivar did not influence L. monocytogenes (p>0.05). Populations of L. monocytogenes on stem scars of cantaloupes stored at 25 degrees C increased by 1-2 log CFU/melon on day 1, and were significantly greater than those on cantaloupes stored at 4 degrees C or 10 degrees C (p<0.05), which remained constant or increased by approximately 0.3 log CFU/melon, respectively, over the same time period. A decrease of 2-5 log CFU/melon of L. monocytogenes occurred on the rinds of cantaloupes during storage by day 7, and were not significantly different at the three different storage temperatures (p>0.05). In trials performed in rind juice extracts, populations of L. monocytogenes decreased by 3 log CFU/mL when stored at 25 degrees C by day 3, but grew by 3-4 log CFU/mL when stored at 4 degrees C over 7days. Overall, site of contamination and storage temperature influenced the survival of L. monocytogenes on cantaloupes more than cantaloupe cultivar type. PMID- 27376680 TI - A first-principles study of the thermodynamic and electronic properties of Mg and MgH2 nanowires. AB - In this article, we studied the thermodynamic and electronic properties of Mg and MgH2 nanowires with different diameters, and elucidated why MgH2 nanowires are good hydrogen storage materials through first-principles calculations. Previous experiments have shown that the orientation relationship between Mg and MgH2 nanowires is the Mg[0001] direction parallel to the MgH2[110] direction. In our calculations, Mg nanowires oriented along the [0001] direction and MgH2 nanowires oriented along the [110] direction were built from bulk Mg and MgH2 crystals, respectively. We found that as the diameters of Mg and MgH2 nanowires decrease, Mg and MgH2 nanowires become more unstable, and the hydrogen desorption energies and temperatures of MgH2 nanowires decrease. That is, the thinner the MgH2 nanowires get, the more dramatically hydrogen desorption temperatures (Td) will decrease. Meanwhile, we also found that when the diameters of MgH2 nanowires are larger than 1.94 nm, the Td almost maintain the same value at about 440 K, only about 40 K lower than that of bulk MgH2 crystal; if the diameters are less than 1.94 nm, the Td reduce very quickly. In particular, compared with bulk MgH2 crystal, the Td of the thinnest MgH2 nanowire with a diameter of 0.63 nm can be reduced by 164 K. In addition, the electronic structure calculations showed that Mg nanowires are metals, while MgH2 nanowires are semiconductors. In particular, our results showed that the electronic structures of MgH2 nanowires are influenced by the surface effect and quantum size effect. That is to say, the band gaps of MgH2 nanowires are controlled by surface electronic states and the size of MgH2 nanowires. PMID- 27376679 TI - Comparison of N-acetylcysteine and cysteine in their ability to replenish intracellular cysteine by a specific fluorescent probe. AB - A specific fluorescent probe, designed by a substitution-rearrangement mechanism, can discriminate cysteine from other thiols. Using this probe, N-acetylcysteine is revealed to be superior to cysteine to replenish intracellular cysteine in cells. PMID- 27376681 TI - Topological insulators and superconductivity: The integrity of two sides. PMID- 27376682 TI - Mechanical plasticity of cells. AB - Under mechanical loading, most living cells show a viscoelastic deformation that follows a power law in time. After removal of the mechanical load, the cell shape recovers only incompletely to its original undeformed configuration. Here, we show that incomplete shape recovery is due to an additive plastic deformation that displays the same power-law dynamics as the fully reversible viscoelastic deformation response. Moreover, the plastic deformation is a constant fraction of the total cell deformation and originates from bond ruptures within the cytoskeleton. A simple extension of the prevailing viscoelastic power-law response theory with a plastic element correctly predicts the cell behaviour under cyclic loading. Our findings show that plastic energy dissipation during cell deformation is tightly linked to elastic cytoskeletal stresses, which suggests the existence of an adaptive mechanism that protects the cell against mechanical damage. PMID- 27376683 TI - Plasmon-driven chemical synthesis: Growing gold nanoprisms with light. PMID- 27376684 TI - Topological edge states in a high-temperature superconductor FeSe/SrTiO3(001) film. AB - Superconducting and topological states are two most intriguing quantum phenomena in solid materials. The entanglement of these two states, the topological superconducting state, will give rise to even more exotic quantum phenomena. While many materials are found to be either a superconductor or a topological insulator, it is very rare that both states exist in one material. Here, we demonstrate by first-principles theory as well as scanning tunnelling spectroscopy and angle-resolved photoemission spectroscopy experiments that the recently discovered 'two-dimensional (2D) superconductor' of single-layer FeSe also exhibits 1D topological edge states within an energy gap of ~40 meV at the M point below the Fermi level. It is the first 2D material that supports both superconducting and topological states, offering an exciting opportunity to study 2D topological superconductors through the proximity effect. PMID- 27376685 TI - Pursuing prosthetic electronic skin. AB - Skin plays an important role in mediating our interactions with the world. Recreating the properties of skin using electronic devices could have profound implications for prosthetics and medicine. The pursuit of artificial skin has inspired innovations in materials to imitate skin's unique characteristics, including mechanical durability and stretchability, biodegradability, and the ability to measure a diversity of complex sensations over large areas. New materials and fabrication strategies are being developed to make mechanically compliant and multifunctional skin-like electronics, and improve brain/machine interfaces that enable transmission of the skin's signals into the body. This Review will cover materials and devices designed for mimicking the skin's ability to sense and generate biomimetic signals. PMID- 27376686 TI - Polyvinylpyrrolidone-induced anisotropic growth of gold nanoprisms in plasmon driven synthesis. AB - After more than a decade, it is still unknown whether the plasmon-mediated growth of silver nanostructures can be extended to the synthesis of other noble metals, as the molecular mechanisms governing the growth process remain elusive. Herein, we demonstrate the plasmon-driven synthesis of gold nanoprisms and elucidate the details of the photochemical growth mechanism at the single-nanoparticle level. Our investigation reveals that the surfactant polyvinylpyrrolidone preferentially adsorbs along the nanoprism perimeter and serves as a photochemical relay to direct the anisotropic growth of gold nanoprisms. This discovery confers a unique function to polyvinylpyrrolidone that is fundamentally different from its widely accepted role as a crystal-face-blocking ligand. Additionally, we find that nanocrystal twinning exerts a profound influence on the kinetics of this photochemical process by controlling the transport of plasmon-generated hot electrons to polyvinylpyrrolidone. These insights establish a molecular-level description of the underlying mechanisms regulating the plasmon-driven synthesis of gold nanoprisms. PMID- 27376687 TI - Structure and dynamics of the retro-form of the bacteriophage T5 endolysin. AB - Using high-resolution NMR spectroscopy we conducted a comparative analysis of the structural and dynamic properties of the bacteriophage T5 endolysin (EndoT5) and its retro-form; i.e., a protein with the reversed direction of the polypeptide chain (R-EndoT5). We show that structurally, retro-form can be described as the molten globule-like polypeptide that is easily able to form large oligomers and aggregates. To avoid complications associated with this high aggregation propensity of the retro protein, we compared EndoT5 and R-EndoT5 in the presence of strong denaturants. This analysis revealed that these two proteins possess different internal dynamics in solutions containing 8M urea, with the retro-form being characterized by larger dimensions and slower internal dynamics. We also show that in the absence of denaturant, both forms of the bacteriophage T5 endolysin are able to interact with micelles formed by the zwitterionic detergent dodecylphosphocholine (DPC), and that the formation of the protein-micelle complexes leads to the significant structural rearrangement of polypeptide chain and to the formation of stable hydrophobic core in the R-Endo T5. PMID- 27376688 TI - Optimisation of triple therapy for patients with chronic hepatitis C: a systematic review. AB - BACKGROUND: Triple therapy with Pegylated-Interferon alpha (PEG IFNalpha)/Ribavirin (RBV) and Boceprevir (Boc) or Telaprevir (Tel) significantly improved sustained virological response (SVR) rates for patients with genotype 1 HCV infection compared to PEG-IFNalpha/RBV alone (dual therapy). However, less is known about factors associated with rates of SVR and of adverse events (AEs). MATERIAL AND METHODS: The aim of this systematic review was to evaluate the evidence regarding the factors affecting response and rate of AEs associated with triple therapy. We performed systematic electronic searches in Medline, Embase, Scopus and Central as well as a list of reference literature. We included randomised controlled trials examining triple therapy compared with dual therapy and reporting data according to patients features and about AEs. Odds ratios (OR) were pooled using either fixed or random effect model, as appropriate. RESULTS: We included data from 14 studies. Treatment with triple therapy increased SVR rate compared to dual therapy especially in patients previously treated with PEG IFNalpha/RBV and with increased pretreatment alanine aminotransferase (ALT) levels. Higher rate of serious AEs and treatment discontinuation due to AEs was also observed particularly in treatment-experienced patients. CONCLUSIONS: The present study shows how improved results of triple therapy are mainly observed in some patients' subsets and are accompanied by increased risk of AEs compared to dual therapy. These results might be useful for optimising treatment of chronic hepatitis C when IFN-free regimens are unavailable. PMID- 27376689 TI - Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition. AB - Here we show that acute myeloid leukemia (AML) cells require the BRD9 subunit of the SWI-SNF chromatin-remodeling complex to sustain MYC transcription, rapid cell proliferation and a block in differentiation. Based on these observations, we derived small-molecule inhibitors of the BRD9 bromodomain that selectively suppress the proliferation of mouse and human AML cell lines. To establish these effects as on-target, we engineered a bromodomain-swap allele of BRD9 that retains functionality despite a radically altered bromodomain pocket. Expression of this allele in AML cells confers resistance to the antiproliferative effects of our compound series, thus establishing BRD9 as the relevant cellular target. Furthermore, we used an analogous domain-swap strategy to generate an inhibitor resistant allele of EZH2. To our knowledge, our study provides the first evidence for a role of BRD9 in cancer and reveals a simple genetic strategy for constructing resistance alleles to demonstrate on-target activity of chemical probes in cells. PMID- 27376690 TI - A reactivity-based probe of the intracellular labile ferrous iron pool. AB - Improved methods for studying intracellular reactive Fe(II) are of significant interest for studies of iron metabolism and disease-relevant changes in iron homeostasis. Here we describe a highly selective reactivity-based probe in which a Fenton-type reaction with intracellular labile Fe(II) leads to unmasking of the aminonucleoside puromycin. Puromycin leaves a permanent and dose-dependent mark on treated cells that can be detected with high sensitivity and precision using a high-content, plate-based immunofluorescence assay. Using this new probe and screening approach, we detected alteration of cellular labile Fe(II) in response extracellular iron conditioning, overexpression of iron storage and/or export proteins, and post-translational regulation of iron export. We also used this new tool to demonstrate that labile Fe(II) pools are larger in cancer cells than in nontumorigenic cells. PMID- 27376693 TI - Population data of 15 autosomal STR loci in Chinese Han population from Jiangsu Province, Eastern China. PMID- 27376691 TI - Tbx16 regulates hox gene activation in mesodermal progenitor cells. AB - The transcription factor T-box 16 (Tbx16, or Spadetail) is an essential regulator of paraxial mesoderm development in zebrafish (Danio rerio). Mesodermal progenitor cells (MPCs) fail to differentiate into trunk somites in tbx16 mutants and instead accumulate within the tailbud in an immature state. However, the mechanisms by which Tbx16 controls mesoderm patterning have remained enigmatic. We describe here the use of photoactivatable morpholino oligonucleotides to determine the Tbx16 transcriptome in MPCs. We identified 124 Tbx16-regulated genes that were expressed in zebrafish gastrulae, including several developmental signaling proteins and regulators of gastrulation, myogenesis and somitogenesis. Unexpectedly, we observed that a loss of Tbx16 function precociously activated posterior hox genes in MPCs, and overexpression of a single posterior hox gene was sufficient to disrupt MPC migration. Our studies support a model in which Tbx16 regulates the timing of collinear hox gene activation to coordinate the anterior-posterior fates and positions of paraxial MPCs. PMID- 27376692 TI - Tolerance of Vascularized Islet-Kidney Transplants in Rhesus Monkeys. AB - We previously reported that transplantation (Tx) of prevascularized donor islets as composite islet-kidneys (IK) reversed diabetic hyperglycemia in both miniature swine and baboons. In order to enhance this strategy's potential clinical applicability, we have now combined this approach with hematopoietic stem cell (HSC) Tx in an attempt to induce tolerance in nonhuman primates. IKs were prepared by isolating islets from 70% partial pancreatectomies and injecting them beneath the autologous renal capsule of five rhesus monkey donors at least 3 months before allogeneic IK Tx. HSC Tx was performed after mobilization and leukapheresis of the donors and conditioning of the recipients with total body irradiation, T cell depletion, and cyclosporine. One IK was harvested for histologic analysis and four were transplanted into diabetic recipients. IK Tx was performed either 20-22 (n = 3) or 208 (n = 1) days after HSC Tx. All animals accepted IKs without rejection. All recipients required >20 U/day insulin before IK Tx to maintain <200 mg/dL, whereas after IK Tx, three animals required minimal doses of insulin (1-3 U/day) and one animal was insulin free. These results constitute a proof-of-principle that this IK tolerance strategy may provide a cure for both end-stage renal disease and diabetes without the need for immunosuppression. PMID- 27376694 TI - A novel cell culture model as a tool for forensic biology experiments and validations. AB - To improve and advance DNA forensic casework investigation outcomes, extensive field and laboratory experiments are carried out in a broad range of relevant branches, such as touch and trace DNA, secondary DNA transfer and contamination confinement. Moreover, the development of new forensic tools, for example new sampling appliances, by commercial companies requires ongoing validation and assessment by forensic scientists. A frequent challenge in these kinds of experiments and validations is the lack of a stable, reproducible and flexible biological reference material. As a possible solution, we present here a cell culture model based on skin-derived human dermal fibroblasts. Cultured cells were harvested, quantified and dried on glass slides. These slides were used in adhesive tape-lifting experiments and tests of DNA crossover confinement by UV irradiation. The use of this model enabled a simple and concise comparison between four adhesive tapes, as well as a straightforward demonstration of the effect of UV irradiation intensities on DNA quantity and degradation. In conclusion, we believe this model has great potential to serve as an efficient research tool in forensic biology. PMID- 27376695 TI - Synthesis and in vitro safety assessment of magnetic bacterial cellulose with porcine aortic smooth muscle cells. AB - Bacterial cellulose (BC) has been used as a scaffold for tissue regeneration (TR). Improving functional TR requires highly selective strategies for specific cell attraction. Embedding iron oxide nanoparticles into a BC matrix can drive magnetically labeled cells to specific tissues where they may begin to heal injured tissue. This article focuses on characterization and in vitro toxicity assessment of magnetic BC (MBC). We proposed to detect the production of radical oxygen species (ROS), esterase activity, and apoptosis to study cytotoxic interactions of MBC within its bioenvironment. Morphological characterization was performed using scanning electron microscopy where evidence shows that the diameter of MBC fibers compared to BC fibers was 33% smaller, and the pore areas were 25% bigger. Cytotoxicity assays in porcine aortic smooth muscle cells exposed for 24 hours to BC, MBC, and poly(ethylene glycol)-coated MBC (MBC-PEG) reveals 96% viability and 9% ROS production for MBC-PEG. In contrast, 25% of cells exposed to MBC were apoptotic, suggesting that even when the cells were metabolically active, MBC can induce damage. These outcomes support the need for more integral assessment in the hopes of assessing the potential biosafety and uses of nanocomposites for TR. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2801-2809, 2016. PMID- 27376696 TI - Self-reported depression in psoriasis is associated with subclinical vascular diseases. AB - BACKGROUND AND AIMS: Psoriasis is a chronic inflammatory disorder associated with vascular inflammation, measured by 18-fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG PET/CT), and an increased risk of myocardial infarction. Patients with psoriasis are also more likely to suffer from comorbid depression. Whether depression accelerates the development of subclinical atherosclerosis in psoriasis is unknown. METHODS: Patients were selected from within a larger psoriasis cohort. Those who reported a history of depression (N = 36) on survey were matched by age and gender to patients who reported no history of psychiatric illness (N = 36). Target-to-background ratio from FDG PET/CT was used to assess aortic vascular inflammation and coronary CT angiography scans were analyzed to determine coronary plaque burden. Multivariable linear regression was performed to understand the effect of self reported depression on vascular inflammation and coronary plaque burden after adjustment for Framingham risk (standardized beta reported). RESULTS: In unadjusted analyses, vascular inflammation and coronary plaque burden were significantly increased in patients with self-reported depression as compared to patients with psoriasis alone. After adjustment for Framingham Risk Score, vascular inflammation (beta = 0.26, p = 0.02), total plaque burden (beta = 0.17, p = 0.03), and non-calcified burden (beta = 0.17, p = 0.03) were associated with self-reported depression. CONCLUSIONS: Self-reported depression in psoriasis is associated with increased vascular inflammation and coronary plaque burden. Depression may play an important role in promoting subclinical atherosclerosis beyond traditional cardiovascular risk factors. PMID- 27376698 TI - The effect of consuming low- versus high-glycemic index meals after exercise on postprandial blood lipid response following a next-day high-fat meal. AB - BACKGROUND/OBJECTIVES: Exercise performed shortly before (that is, within half a day of) a high-fat meal is beneficial for stimulating fat oxidation after the meal and reducing postprandial triglycerides (TG). This benefit of exercise is unfortunately negated if the after-exercise food choice to replace the calories expended during exercise is one containing high-glycemic index (HGI) carbohydrates. We determined the effect of consuming low-glycemic index (LGI) carbohydrates after an exercise session on fat oxidation and TG after a subsequent high-fat meal. SUBJECTS/METHODS: Using a randomized, counterbalanced crossover design, 23 overweight or obese individuals (body mass index ?25 kg m( 2)) performed: walking exercise (90 min) at 1800 h followed by no meal (EX); exercise followed by a meal with LGI carbohydrates (that is, lentils, EX-LGI); exercise followed by a meal with HGI carbohydrates (that is, instant potatoes, white bread, EX-HGI); and a control condition with no exercise or meal. After a 10-h overnight fast, participants were given a standardized high-fat meal. Fat oxidation was estimated before and for 6 h after this meal from respiratory gas measures and TG determined from blood samples. RESULTS: Fat oxidation (mean+/ s.d.) was higher with EX (6.9+/-1.7 g h(-1)) than EX-HGI (6.3+/-1.6 g h(-1); P=0.007) and Control (5.9+/-1.7 g h(-1); P=0.00002), and EX-LGI (6.6+/-1.7 g h( 1)) was higher than Control (P=0.002). TG total area under the curve was 18-32% lower with EX and EX-LGI compared with control (P=0.0005 and P=0.0001, respectively) and EX-HGI (P=0.05 and P=0.021, respectively). CONCLUSIONS: A meal containing HGI carbohydrates consumed after an evening exercise session cancels the beneficial effect of exercise for stimulating fat oxidation and lowering TG after a subsequent high-fat meal, whereas consuming a post-exercise meal with LGI carbohydrates retains the positive effect of exercise. PMID- 27376697 TI - Defective phosphoinositide metabolism in autism. AB - Phosphoinositides are essential components of lipid membranes and crucial regulators of many cellular functions, including signal transduction, vesicle trafficking, membrane receptor localization and activity, and determination of membrane identity. These functions depend on the dynamic and highly regulated metabolism of phosphoinositides and require finely balanced activity of specific phosphoinositide kinases and phosphatases. There is increasing evidence from genetic and functional studies that these enzymes are often dysregulated or mutated in autism spectrum disorders; in particular, phosphoinositide 3-kinases and their regulatory subunits appear to be affected frequently. Examples of autism spectrum disorders with defective phosphoinositide metabolism are fragile X syndrome and autism disorders associated with mutations in the phosphoinositide 3-phosphatase tensin homolog deleted on chromosome 10 (PTEN), but recent genetic analyses also suggest that select nonsyndromic, idiopathic forms of autism may have altered activity of phosphoinositide kinases and phosphatases. Isoform specific inhibitors for some of the phosphoinositide kinases have already been developed for cancer research and treatment, and a few are being evaluated for use in humans. Altogether, this offers exciting opportunities to explore altered phosphoinositide metabolism as a therapeutic target in individuals with certain forms of autism. This review summarizes genetic and functional studies identifying defects in phosphoinositide metabolism in autism and related disorders, describes published preclinical work targeting phosphoinositide 3 kinases in neurological diseases, and discusses the opportunities and challenges ahead to translate these findings from animal models and human cells into clinical application in humans. (c) 2016 Wiley Periodicals, Inc. PMID- 27376701 TI - Perspectives for microbial community composition in anaerobic digestion: from abundance and activity to connectivity. AB - Microbial management in anaerobic digestion is mainly focused on physically present and metabolically active species. Because of its complexity and operation near the thermodynamic equilibria, it is equally important to address functional regulation, based on spatial organisation and interspecies communication. Further establishment of the knowledge on microbial communication in anaerobic digestion through quorum sensing and nanowires is needed. Methods to detect centres of concentrated activity, related to the presence of highly active and well connected species that take a central role in the anaerobic digestion process, have to be optimized. Bioaugmentation could serve as a crucial tool to introduce keystone species that may create or sustain such centres. Functional stability can be maintained by keeping the microbial community active. This results in a clear trade-off between functionally active and redundant microorganisms as primary basis for microbial community organization. Finally, a microbial community based prediction strategy for advanced process control is formulated. PMID- 27376699 TI - Differences in glycemic control across world regions: a post-hoc analysis in patients with type 2 diabetes mellitus on dual antidiabetes drug therapy. AB - OBJECTIVE: This post-hoc analysis of the EDGE (Effectiveness of Diabetes control with vildaGliptin and vildagliptin/mEtformin) study assessed inter-regional differences in baseline characteristics and response to treatment intensification with dual oral antidiabetes drugs (OADs) in patients with type 2 diabetes mellitus (T2DM). METHODS: Patients with T2DM inadequately controlled with first line monotherapy were assigned to receive a dipeptidyl peptidase-4 (DPP-4) inhibitor, vildagliptin, or comparator OADs as add-on dual therapy. The primary effectiveness end point (PEP) was achieving glycated hemoglobin (HbA1c) reduction >0.3% without hypoglycemia, peripheral edema, discontinuation owing to gastrointestinal events or weight gain ?5% at 12 months. The secondary effectiveness end point (SEP) was achieving HbA1c of <7% without hypoglycemia or weight gain ?3% at 12 months. RESULTS: Baseline characteristics of patients (N=43 791), including mean HbA1c (8.2%), varied across regions. Baseline age (62.3 years) and T2DM duration (6.3 years) were greater in patients from Europe than those from India and the Middle East (age: 51.8 and 52.1 years; T2DM duration: 4.3 and 4.2 years, respectively). The probability of achieving PEP with dual therapy was higher in India (odds ratio (OR): 1.5), Latin America (OR: 1.2) and Middle East (OR: 2.0) than in Europe (OR: 0.8) and East Asia (OR: 0.3). Achievement of SEP in patients receiving dual therapy was greater in Latin America (OR: 1.7) and Middle East (OR: 1.7). Vildagliptin add-on therapy allowed more patients to achieve SEP across regions. Women aged ?45 years less often attained glycemic target (HbA1c<7%) without significant weight gain ?5% compared with women aged <45 years (OR: 0.876, 95% confidence interval: 0.774, 0.992; P=0.037). CONCLUSIONS: Baseline HbA1c and T2DM duration differed considerably across all regions. Treatment intensification with second OAD, particularly with a DPP-4 inhibitor vildagliptin, resulted in good treatment response without tolerability issues despite delayed intensification of failing monotherapy across regions. PMID- 27376700 TI - Association of pasta consumption with body mass index and waist-to-hip ratio: results from Moli-sani and INHES studies. AB - BACKGROUND/OBJECTIVES: Pasta as a traditional component of Mediterranean diet (MeD) in Italy has not been studied in detail in the management of body weight. This study aimed at evaluating the association of pasta intake with body mass index (BMI) and waist-to-hip ratio, in two large epidemiological datasets. SUBJECTS/METHODS: A total of 14 402 participants aged ?35 years randomly recruited from the general population of the Molise region (Moli-sani cohort) and 8964 participants aged >18 years from all over Italy (Italian Nutrition & HEalth Survey, INHES) were separately analyzed. The European Prospective Investigation into Cancer and Nutrition (EPIC)-food frequency questionnaire and one 24-h dietary recall were used for dietary assessment. Weight, height, waist and hip circumference were measured in Moli-sani or self-reported in INHES. Residuals methodology corrected for either total energy intake or body weight was used for the analysis of pasta intake. RESULTS: Higher pasta intake was associated with better adhesion to MeD in both genders (P for both<0.001). In the Moli-sani study, after multivariable analysis, pasta-energy residuals were negatively associated with BMI in women but not in men (beta-coef=-0.007, P=0.003 for women and beta-coef=-0.001, P=0.58 for men). When pasta intake-body weight residuals were used, pasta intake was significantly and negatively associated with BMI in crude and multi-adjusted models (including adhesion to MeD) in both genders and Moli-sani and INHES studies (for all beta-coef<0, P<0.05). In the Moli-sani study, pasta-body weight residuals were significantly and negatively associated with waist and hip circumference and waist-to-hip ratio (for all beta-coef<0, P<0.05). CONCLUSIONS: As a traditional component of MeD, pasta consumption was negatively associated with BMI, waist circumference and waist-to-hip ratio and with a lower prevalence of overweight and obesity. PMID- 27376702 TI - Assessment of three methods of geometric image reconstruction for digital subtraction radiography. AB - OBJECTIVES: To evaluate three methods of geometric image reconstruction for digital subtraction radiography (DSR). METHODS: Digital periapical radiographs were acquired of 24 teeth with the X-ray tube at 6 different geometric configurations of vertical (V) and horizontal (H) angles: V0 degrees H0 degrees , V0 degrees H10 degrees , V10 degrees H0 degrees , V10 degrees H10 degrees , V20 degrees H0 degrees and V20 degrees H10 degrees . All 144 images were registered in pairs (Group V0 degrees H0 degrees + 1 of the 6 groups) 3 times by using the Emago((r)) (Oral Diagnostic Systems, Amsterdam, Netherlands) with manual selection and Regeemy with manual and automatic selections. After geometric reconstruction on the two software applications under different modes of selection, all images were subtracted and the standard deviation of grey values was obtained as a measure of image noise. All measurements were repeated after 15 days to evaluate the method error. Values of image noise were statistically analyzed by one-way ANOVA for differences between methods and between projection angles, followed by Tukey's test at a level of significance of 5%. RESULTS: Significant differences were found between most of the projection angles for the three reconstruction methods. Image subtraction after manual selection-based reconstruction on Regeemy presented the lowest values of image noise, except on group V0 degrees H0 degrees . The groups V10 degrees H0 degrees and V20 degrees H0 degrees were not significantly different between the manual selection-based reconstruction in Regeemy and automatic selection-based reconstruction in Regeemy methods. CONCLUSIONS: The Regeemy software on manual mode revealed better quality of geometric image reconstruction for DSR than the Regeemy on automatic mode and the Emago on manual mode, when the radiographic images were obtained at V and H angles used in the present investigation. PMID- 27376703 TI - The use of cone beam CT in achieving unipedicular spinal augmentation. AB - OBJECTIVE: To assess the feasibility of cone beam CT (CBCT) in achieving unipedicular access during spinal cement augmentation. METHODS: A retrospective review of all patients who underwent CBCT-guided unipedicular spinal augmentation procedures between 1 January 2012 and 15 June 2015 was performed. 59 patients (43 females 16 males; mean-age, 74.0 years; range, 52-90 years) underwent unipedicular spinal augmentation in 78 vertebral levels (T5-T9, n = 14; T10-L2, n = 42; L3-L5, n = 22). Degree of cross-over in contralateral hemivertebral body, complications and 30-day mortality were recorded. RESULTS: 97% (76/78) of procedures were technically successful. Two procedures failed owing to vertebral sclerosis. For vertebroplasty, all cases (6/6) demonstrated cross-over filling of cement and 50% (3/6) showed cement cross-over >50% of contralateral half of the vertebral body. For kyphoplasty, 13 out of 15 procedures demonstrated balloon and cement cross-over >50% of contralateral half of the vertebral body. Two kyphoplasty procedures required the second pedicle after midline cross-over of cement failed. Of the kyphoplasty procedures that were successfully performed with the unipedicular approach, 76.9% (10/13) showed cement cross-over >50% of contralateral half of the vertebral body. For stentoplasty, all cases (55/55) showed midline stent-cement complex cross-over and 78.2% (43/55) exhibited stent cement complex cross-over >50% of contralateral half of the vertebral body. There was no major complication or mortality. Minor complications included asymptomatic cement extravasation (6.4%, n = 5) and self-limiting haematoma (1.3%, n = 1). CONCLUSION: Unipedicular access for spinal augmentation procedures is achieved at a high success rate with the use of CBCT. ADVANCES IN KNOWLEDGE: This article describes the novel use of CBCT to achieve unipedicular spinal augmentation. Unipedicular spinal augmentation has the potential to reduce risk, duration, radiation and cost while achieving similar results. PMID- 27376704 TI - A Single Methylene Group in Oligoalkylamine-Based Cationic Polymers and Lipids Promotes Enhanced mRNA Delivery. AB - The development of chemically modified mRNA holds great promise as a new class of biologic therapeutics. However, the intracellular delivery and endosomal escape of mRNA encapsulated in nanoparticles has not been systematically investigated. Here, we synthesized a diverse set of cationic polymers and lipids from a series of oligoalkylamines and subsequently characterized their mRNA delivery capability. Notably, a structure with an alternating alkyl chain length between amines showed the highest transfection efficiency, which was linked to a high buffering capacity in a narrow range of pH 6.2 to 6.5. Variation in only one methylene group resulted in enhanced mRNA delivery to both the murine liver as well as porcine lungs after systemic or aerosol administration, respectively. These findings reveal a novel fundamental structure-activity relationship for the delivery of mRNA that is independent of the class of mRNA carrier and define a promising new path of exploration in the field of mRNA therapeutics. PMID- 27376705 TI - Regiospecific Hydration of N-(Diphenylphosphinoyl)propargyl Amines: Synthesis of beta-Amino Ketones by Au(III) Catalysis. AB - A Au(III)-catalyzed regiospecific hydration of N-(diphenylphosphinoyl)propargyl amines has been developed to produce various beta-amino ketones. These reactions are conducted in the presence of NaAuCl4.2H2O (10 mol %) in a mixed solvent of EtOH/H2O/CH2Cl2 (4:1:1) at room temperature to give the products in 45-71% yield. The high enantiomeric purity of a chiral N-(diphenylphosphinoyl)propargyl amine (85% ee) is maintained after hydration, which makes this method useful for the asymmetric synthesis of chiral beta-amino ketones. Reduction of a beta-amino ketone product with Zn(BH4)2 gives a 1,3-amino alcohol with modest diastereoselectivity. PMID- 27376706 TI - Efficacy of sofosbuvir plus ribavirin in treatment-naive patients with genotype-1 and -3 HCV infection: results from a Russian Phase IIIb study. AB - BACKGROUND: In this Phase IIIb study, we evaluated the efficacy and safety of the oral nucleotide analogue inhibitor sofosbuvir plus ribavirin, with special attention given to viral resistance, in Russian patients with HCV genotype-1 or 3. METHODS: Treatment-naive patients with and without compensated cirrhosis were randomized (1:1) to receive 16 or 24 weeks of once-daily sofosbuvir 400 mg plus twice-daily oral ribavirin 1,000 or 1,200 mg/day. The primary efficacy end point was the proportion of patients with sustained viral response 12 weeks after the end of treatment (SVR12). Viral resistance testing was performed by deep sequencing on all baseline samples and for patients who experienced virological failure. RESULTS: SVR12 rates for patients with genotype-1 HCV were 50% and 76% for those in the 16-week and 24-week groups, respectively, and for patients with genotype-3 HCV, SVR12 rates were 87% and 90% for patients in the 16-week and 24 weeks groups, respectively. Genotype-1 patients with the L159F resistance associated variant who received 16 weeks of treatment had lower SVR12 rates than those without, but in patients who received 24 weeks of treatment, response rates were similar in those with and without L159F (80% versus 74%). Sofosbuvir plus ribavirin was well tolerated with no deaths, adverse event-related study drug discontinuations, or grade 3 or 4 adverse events, and few grade 3 or 4 laboratory abnormalities. CONCLUSIONS: Sofosbuvir plus ribavirin for 16 or 24 weeks was associated with a high SVR rate in patients with HCV genotype-3. Among HCV genotype-1b patients, the presence of the L159F variant at baseline was associated with a lower SVR rate in those treated for 16 weeks but not in those treated for 24 weeks. Sofosbuvir plus ribavirin was safe and well tolerated regardless of treatment duration. Clinicaltrials.gov number NCT01896193. PMID- 27376707 TI - Ferrocenyl Paclitaxel and Docetaxel Derivatives: Impact of an Organometallic Moiety on the Mode of Action of Taxanes. AB - A series of ferrocenyl analogues and derivatives of paclitaxel and docetaxel were synthesised and assayed for their antiproliferative/cytotoxic effects, impact on the cell cycle distribution and ability to induce tubulin polymerisation. The replacement of the 3'-N-benzoyl group of paclitaxel with a ferrocenoyl moiety, in particular, led to formation of an analogue that was at least one order of magnitude more potent in terms of antiproliferative activity than the parent compound (IC50 values of 0.11 versus 1.11 MUm, respectively), but still preserved the classical taxane mode of action, that is, microtubule stabilisation leading to mitotic arrest. Molecular docking studies revealed an unexpected binding pocket in the tubulin structure for the ferrocenoyl group introduced in the paclitaxel backbone. PMID- 27376708 TI - Freezing Molecular Orientation under Stretch for High Mechanical Strength but Anisotropic Hydrogels. AB - The poor mechanical strength of hydrogels has largely limited their wide applications, and improving hydrogels' mechanical strength is a hot and important topic in the hydrogel research field. Although many successful strategies have been proposed to improve hydrogels' mechanical strength during the past decades, a hydrogel with a tensile stress surpassing dozens of mega Pascal is desirable, yet still a big challenge. To address this issue, the Fe(3+) -mediated physical crosslinking formed under stretch conditions was employed in a chemically crosslinked poly (acrylamide-co-acrylic acid) network to achieve a dual crosslinked hydrogel. The expected molecular orientation occurs under stretch and allows the maximumu chelating interaction between pendant carboxylic anions and Fe(3+) and molecules conformation being frozen, leading to the mechanical strength improving dramatically. As a result, an unprecedentedly high mechanical strength, but anisotropic dual-crosslinked hydrogel was obtained. By optimizing the experimental parameters, the nominal tensile stress along pre-stretching direction can reach as high as ~40 MPa with elastic modulus of ~40 MPa at large strain (>200%). In addition, the molecular orientation also leads to big difference of mechanical performance between parallel and perpendicular direction. PMID- 27376709 TI - Local Grafting of Ionic Liquid in Poly(vinylidene fluoride) Amorphous Region and the Subsequent Microphase Separation Behavior in Melt. AB - Polymer-based nanostructures can be generally created by self-assembly of block copolymers that are commonly synthesized by living radical polymerization. In this study, a new strategy is proposed to fabricate block-like copolymers by using the template of binary phase structure of semicrystalline polymers. Poly(vinylidene fluoride) (PVDF) is thermodynamically miscible with an unsaturated ionic liquid (IL) (1-vinyl-3-ethylimidazolium tetrafluoroborate) in the melt and IL molecules are expelled out from the crystalline parts during the crystallization of PVDF. Therefore, the IL molecules are only located at the amorphous region of PVDF crystals. The electron beam irradiation of the IL incorporated PVDF leads to the local grafting of IL molecules onto the PVDF molecular chains in the amorphous region, so block-like grafting polymer chains of crystalline PVDF-b-(amorphous PVDF-g-IL)-b-crystalline PVDF can be achieved. The subsequent heating of the irradiated sample induces the microphase separation of PVDF-g-IL from the ungrafted PVDF chains. PMID- 27376710 TI - Posturographic limits of stability can predict the increased risk of falls in elderly patients with instability? AB - CONCLUSIONS: There was a difference in average score of the sensory organization test (SOT) of the case group (elderly instability) compared to the control group (healthy subjects). Cases had worse scores on the limits of stability (LOS) than controls, but were only able to confirm statistically significant differences in the movement velocity. OBJECTIVE: To study the LOS of elderly patients with instability vs healthy subjects of the same age to try to explain the increased risk of falls in elderly patients with instability. METHODS: Fifty individuals >=65 years, 30 cases (at least one of the next inclusion criteria: >=1 fall in the last 12 months, >15 s or some support in the timed up and go test, composite <68 in SOT, >=1 fall during production of the SOT) compared to 20 controls. Postural study: SOT and LOS, Smart Equitest Neurocom(r) platform. STATISTICAL ANALYSIS: t-Student test (p < 0.05). RESULT: Mean value of overall balance: patients with instability =56% vs controls =77.1% (p < 0.001). Movement velocity: cases =2243 degrees /s vs controls =2860 degrees /s (p = 0.029). The reaction time (cases =1217 s vs controls =1.077 s), excursion (56.95% vs 59.35%) and directional control (56.95% vs 59.35%) differences were not statistically significant. PMID- 27376712 TI - Single-particle spectroscopy of I-III-VI semiconductor nanocrystals: spectral diffusion and suppression of blinking by two-color excitation. AB - Ternary I-III-VI semiconductor nanocrystals have been explored as non-toxic alternatives to II-VI semiconductors for optoelectronic and sensing applications, but large photoluminescence spectral width and moderate brightness restrict their practical use. Here, using single-particle photoluminescence spectroscopy on nanocrystals of (AgIn)xZn2(1-x)S2 we show that the photoluminescence band is inhomogeneously broadened and that size distribution is the dominant factor in the broadening. The residual homogeneous linewidth of individual nanocrystals reaches up to 75% of the ensemble spectral width. Single nanocrystals undergo spectral diffusion which also contributes to the inhomogeneous band. Excitation with two lasers with energies above and below the bandgap reveals coexistence of two emitting donor states within one particle. Spectral diffusion in such particles is due to temporal activation and deactivation of one such state. Filling of a trap state with a lower-energy laser enables optical modulation of photoluminescence intermittency (blinking) and leads to an almost two-fold increase in brightness. PMID- 27376711 TI - Efficacy and safety of liraglutide compared to sulphonylurea during Ramadan in patients with type 2 diabetes (LIRA-Ramadan): a randomized trial. AB - AIMS: Compare effects of liraglutide 1.8 mg and sulphonylurea, both combined with metformin, on glycaemic control in patients with type 2 diabetes (T2D) fasting during Ramadan. MATERIALS AND METHODS: In this up to 33-week, open-label, active controlled, parallel-group trial, adults [glycated haemoglobin (HbA1c) 7%-10% (53 86 mmol/mol); body mass index >=20 kg/m(2) ; intent to fast] were randomized (1:1) >=10 weeks before Ramadan to either switch to once-daily liraglutide (final dose 1.8 mg) or continue pre-trial sulphonylurea at maximum tolerated dose, both with metformin. PRIMARY ENDPOINT: change in fructosamine, a validated marker of short-term glycaemic control, during Ramadan. RESULTS: Similar reductions in fructosamine levels were observed for both groups during Ramadan [liraglutide ( 12.8 umol/L); sulphonylurea (-16.4 umol/L); estimated treatment difference (ETD) 3.51 umol/L (95% CI: -5.26; 12.28); p = 0.43], despite lower fructosamine levels in the liraglutide group at start of Ramadan. Fewer documented symptomatic hypoglycaemic episodes were reported in liraglutide-treated (2%, three subjects) versus sulphonylurea-treated patients (11%, 18 subjects). No severe hypoglycaemic episodes were reported by either group. Body weight decreased more during Ramadan with liraglutide (ETD: -0.54 kg; 95% CI: -0.94;-0.14; p = 0.0091). The proportion of patients reporting adverse events was similar between groups. Liraglutide led to greater HbA1c reduction [ETD: -0.59% (-6.40 mmol/mol), 95% CI: -0.79; -0.38%; 8.63; -4.17 mmol/mol; p < 0.0001]. CONCLUSIONS: Despite lower fructosamine levels and body weight at the beginning of Ramadan, use of liraglutide showed similar glycaemic improvements, fewer hypoglycaemic episodes and greater body weight reduction compared with sulphonylurea. LIRA-Ramadan provides evidence for liraglutide being safe and efficacious for management of T2D during Ramadan fasting. PMID- 27376714 TI - Isolation, Stereochemical Study, and Antioxidant Activity of Benzofuranone Derivatives from a Mangrove-derived Fungus Eurotium rubrum MA-150. AB - Enantiomers of a 2-benzofuran-1(3H)-one derivative [(-)- and (+)-] and four known analogs () were isolated and identified from the culture extract of Eurotium rubrum MA-150, a fungus obtained from the mangrove-derived rizospheric soil. Their structures were established by detailed interpretation of nuclear magnetic resonance (NMR) data and the structure of (+/-)- was confirmed by single-crystal X-ray diffraction analysis. The absolute configuration of the enantiomers (-)- and (+)- was determined by means of online high-performance liquid chromatography - electronic circular dichroism (HPLC-ECD) measurements and time-dependent Density Functional Theory - electronic circular dichroism (TDDFT-ECD) calculations. Compounds (+/-)- as well as and exhibited potent DPPH radical scavenging activities with IC50 values of 1.23, 2.26, and 3.99 MUg/mL, respectively. Chirality 28:581-584, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27376713 TI - Monomeric C-reactive protein and inflammation in age-related macular degeneration. AB - Age-related macular degeneration (AMD) is a devastating disease characterized by central vision loss in elderly individuals. Previous studies have suggested a link between elevated levels of total C-reactive protein (CRP) in the choroid, CFH genotype, and AMD status; however, the structural form of CRP present in the choroid, its relationship to CFH genotype, and its functional consequences have not been assessed. In this report, we studied genotyped human donor eyes (n = 60) and found that eyes homozygous for the high-risk CFH (Y402H) allele had elevated monomeric CRP (mCRP) within the choriocapillaris and Bruch's membrane, compared to those with the low-risk genotype. Treatment of choroidal endothelial cells in vitro with mCRP increased migration rate and monolayer permeability compared to treatment with pentameric CRP (pCRP) or medium alone. Organ cultures treated with mCRP exhibited dramatically altered expression of inflammatory genes as assessed by RNA sequencing, including ICAM-1 and CA4, both of which were confirmed at the protein level. Our data indicate that mCRP is the more abundant form of CRP in human choroid, and that mCRP levels are elevated in individuals with the high risk CFH genotype. Moreover, pro-inflammatory mCRP significantly affects endothelial cell phenotypes in vitro and ex vivo, suggesting a role for mCRP in choroidal vascular dysfunction in AMD. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 27376716 TI - Training wheelchair navigation in immersive virtual environments for patients with spinal cord injury - end-user input to design an effective system. AB - PURPOSE: A user-centred design was used to develop and test the feasibility of an immersive 3D virtual reality wheelchair training tool for people with spinal cord injury (SCI). METHOD: A Wheelchair Training System was designed and modelled using the Oculus Rift headset and a Dynamic Control wheelchair joystick. The system was tested by clinicians and expert wheelchair users with SCI. Data from focus groups and individual interviews were analysed using a general inductive approach to thematic analysis. RESULTS: Four themes emerged: Realistic System, which described the advantages of a realistic virtual environment; a Wheelchair Training System, which described participants' thoughts on the wheelchair training applications; Overcoming Resistance to Technology, the obstacles to introducing technology within the clinical setting; and Working outside the Rehabilitation Bubble which described the protective hospital environment. CONCLUSIONS: The Oculus Rift Wheelchair Training System has the potential to provide a virtual rehabilitation setting which could allow wheelchair users to learn valuable community wheelchair use in a safe environment. Nausea appears to be a side effect of the system, which will need to be resolved before this can be a viable clinical tool. Implications for Rehabilitation Immersive virtual reality shows promising benefit for wheelchair training in a rehabilitation setting. Early engagement with consumers can improve product development. PMID- 27376715 TI - Pharmacological blockage of fibro/adipogenic progenitor expansion and suppression of regenerative fibrogenesis is associated with impaired skeletal muscle regeneration. AB - Acute skeletal muscle injury triggers an expansion of fibro/adipogenic progenitors (FAPs) and a transient stage of fibrogenesis characterized by extracellular matrix deposition. While the perpetuation of such phase can lead to permanent tissue scarring, the consequences of its suppression remain to be studied. Using a model of acute muscle damage we were able to determine that pharmacological inhibition of FAP expansion by Nilotinib, a tyrosine kinase inhibitor with potent antifibrotic activity, exerts a detrimental effect on myogenesis during regeneration. We found that Nilotinib inhibits the damage induced expansion of satellite cells in vivo, but it does not affect in vitro proliferation, suggesting a non cell-autonomous effect. Nilotinib impairs regenerative fibrogenesis by preventing the injury-triggered expansion and differentiation of resident CD45(-):CD31(-):alpha7integrin(-):Sca1(+) mesenchymal FAPs. Our data support the notion that the expansion of FAPs and transient fibrogenesis observed during regeneration play an important trophic role toward tissue-specific stem cells. PMID- 27376717 TI - Superb Electrically Conductive Graphene Fibers via Doping Strategy. AB - Graphene fibers (GFs) with superb electrical conductivity are produced via a chemical doping strategy. The electrical conductivities reach up to 0.77 * 107 2.24 * 107 S m-1 , which are the highest values among all the reported GFs. The combination of lightness, superb conductivity, and easy scalability makes GFs a promising new carbonaceous fiber species with high performance and advanced functionality. PMID- 27376718 TI - The correlation between retrograde leak point pressure and 24-hour pad weight. AB - AIM: To assess the correlation between retrograde leak point pressure (RLPP) and 24-hr pad weight (24PW) in men with post-prostatectomy incontinence. METHODS: We performed RLPP and 24PW measurements on 61 patients with a history of post prostatectomy stress urinary incontinence (SUI). We examined the relationship of RLPP and 24PW. We also reviewed the urodynamic and clinical data of these patients to explain our findings. RESULTS: The mean age was 70 years (SD +/- 7.4, range: 51-87). The mean RLPP was 36.8 cmH2 O (SD +/- 15.3, range: 9-76), the mean 24PW was 499 g (+/-677 g, range: 16.5-3,177 g). There was a good and significant negative correlation between RLPP and 24PW (r = 0.56, P < 0.01). RLPP was able to differentiate between cases of mild/moderate (<400 g) and severe (>=400 g) incontinence. Patients with RLPP <30 cmH2 O had significantly higher 24PW (mean 825 g, median 768 g) when compared with patients with RLPP >30 cmH2 O (mean 257.8 g, median 100 g, P < 0.01). CONCLUSIONS: RLPP could be used as an objective and potentially more reliable substitute to pad weight to objectify and stratify SUI in post-prostatectomy patients. Neurourol. Urodynam. 36:1119-1123, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27376719 TI - Fluoroscopy versus ultrasonography guided mini-percutaneous nephrolithotomy in patients with autosomal dominant polycystic kidney disease. AB - The objective of the study was to compare the therapeutic outcomes between the ultrasonography-guided (USG) and the fluoroscopy-guided (FG) mini-percutaneous nephrolithotomy (MPCNL) for the treatment of large or complex upper urinary tract stones (S.T.O.N.E. scores 5-11) in patients with autosomal dominant polycystic kidney disease (ADPKD). 45 ADPKD patients who were suffering from large or complex upper urinary tract stones (S.T.O.N.E. scores 5-11, mean score 7.6) in 45 renal units were accrued into this retrospective study. They were treated by either USG (20 patients) or FG (25 patients) MPCNL in our center. The treatment results as well as the complications according to the modified Clavien system were assessed and compared. The FG MPCNL group had a higher success rate in accessing the targeted calyces than the USG MPCNL group (96 vs. 70 %, p = 0.048). There was no significant difference observed between the two groups with respect to the operative time, the mean hemoglobin drop, and the stone free rate. The overall operative complications and the perioperative blood transfusion rates were significantly higher in the USG than the FG MPCNL groups, 71.4 vs. 29.2 %, p = 0.011, and 35.7 vs. 4.2 %, p = 0.018, respectively. There was no significant difference between these two groups in terms of major complications (Clavien score 3a-4a) (p = 0.542). In our center, the FG MPCNL was a superior modality to the USG MPCNL in the treatment of large or complex kidney stones in the ADPKD patients. It resulted in higher successful calyceal punctures and less operative complications. PMID- 27376720 TI - On-patient see-through augmented reality based on visual SLAM. AB - PURPOSE: An augmented reality system to visualize a 3D preoperative anatomical model on intra-operative patient is proposed. The hardware requirement is commercial tablet-PC equipped with a camera. Thus, no external tracking device nor artificial landmarks on the patient are required. METHODS: We resort to visual SLAM to provide markerless real-time tablet-PC camera location with respect to the patient. The preoperative model is registered with respect to the patient through 4-6 anchor points. The anchors correspond to anatomical references selected on the tablet-PC screen at the beginning of the procedure. RESULTS: Accurate and real-time preoperative model alignment (approximately 5-mm mean FRE and TRE) was achieved, even when anchors were not visible in the current field of view. The system has been experimentally validated on human volunteers, in vivo pigs and a phantom. CONCLUSIONS: The proposed system can be smoothly integrated into the surgical workflow because it: (1) operates in real time, (2) requires minimal additional hardware only a tablet-PC with camera, (3) is robust to occlusion, (4) requires minimal interaction from the medical staff. PMID- 27376722 TI - Impedance cardiography signal denoising using discrete wavelet transform. AB - Impedance cardiography (ICG) is a non-invasive technique for diagnosing cardiovascular diseases. In the acquisition procedure, the ICG signal is often affected by several kinds of noise which distort the determination of the hemodynamic parameters. Therefore, doctors cannot recognize ICG waveform correctly and the diagnosis of cardiovascular diseases became inaccurate. The aim of this work is to choose the most suitable method for denoising the ICG signal. Indeed, different wavelet families are used to denoise the ICG signal. The Haar, Daubechies (db2, db4, db6, and db8), Symlet (sym2, sym4, sym6, sym8) and Coiflet (coif2, coif3, coif4, coif5) wavelet families are tested and evaluated in order to select the most suitable denoising method. The wavelet family with best performance is compared with two denoising methods: one based on Savitzky-Golay filtering and the other based on median filtering. Each method is evaluated by means of the signal to noise ratio (SNR), the root mean square error (RMSE) and the percent difference root mean square (PRD). The results show that the Daubechies wavelet family (db8) has superior performance on noise reduction in comparison to other methods. PMID- 27376721 TI - A methodological, task-based approach to Procedure-Specific Simulations training. AB - PURPOSE: Procedure-Specific Simulations (PSS) are 3D realistic simulations that provide a platform to practice complete surgical procedures in a virtual-reality environment. While PSS have the potential to improve surgeons' proficiency, there are no existing standards or guidelines for PSS development in a structured manner. METHOD: We employ a unique platform inspired by game design to develop virtual reality simulations in three dimensions of urethrovesical anastomosis during radical prostatectomy. 3D visualization is supported by a stereo vision, providing a fully realistic view of the simulation. The software can be executed for any robotic surgery platform. Specifically, we tested the simulation under windows environment on the RobotiX Mentor. RESULT: Using urethrovesical anastomosis during radical prostatectomy simulation as a representative example, we present a task-based methodological approach to PSS training. The methodology provides tasks in increasing levels of difficulty from a novice level of basic anatomy identification, to an expert level that permits testing new surgical approaches. CONCLUSION: The modular methodology presented here can be easily extended to support more complex tasks. We foresee this methodology as a tool used to integrate PSS as a complementary training process for surgical procedures. PMID- 27376723 TI - Spectral feature extraction of EEG signals and pattern recognition during mental tasks of 2-D cursor movements for BCI using SVM and ANN. AB - Brain computer interface (BCI) is a new communication way between man and machine. It identifies mental task patterns stored in electroencephalogram (EEG). So, it extracts brain electrical activities recorded by EEG and transforms them machine control commands. The main goal of BCI is to make available assistive environmental devices for paralyzed people such as computers and makes their life easier. This study deals with feature extraction and mental task pattern recognition on 2-D cursor control from EEG as offline analysis approach. The hemispherical power density changes are computed and compared on alpha-beta frequency bands with only mental imagination of cursor movements. First of all, power spectral density (PSD) features of EEG signals are extracted and high dimensional data reduced by principle component analysis (PCA) and independent component analysis (ICA) which are statistical algorithms. In the last stage, all features are classified with two types of support vector machine (SVM) which are linear and least squares (LS-SVM) and three different artificial neural network (ANN) structures which are learning vector quantization (LVQ), multilayer neural network (MLNN) and probabilistic neural network (PNN) and mental task patterns are successfully identified via k-fold cross validation technique. PMID- 27376725 TI - Structure and evolution of the gorilla and orangutan growth hormone loci. AB - In primates, the unigenic growth hormone (GH) locus of prosimians expressed primarily in the anterior pituitary, evolved by gene duplications, independently in New World Monkeys (NWM) and Old World Monkeys (OWMs)/apes, to give complex clusters of genes expressed in the pituitary and placenta. In human and chimpanzee, the GH locus comprises five genes, GH-N being expressed as pituitary GH, whereas GH-V (placental GH) and CSHs (chorionic somatomammotropins) are expressed (in human and probably chimpanzee) in the placenta; the CSHs comprise CSH-A, CSH-B and the aberrant CSH-L (possibly a pseudogene) in human, and CSH-A1, CSH-A2 and CSH-B in chimpanzee. Here, the GH locus in two additional great apes, gorilla (Gorilla gorilla gorilla) and orangutan (Pongo abelii), is shown to contain six and four GH-like genes, respectively. The gorilla locus possesses six potentially expressed genes, gGH-N, gGH-V and four gCSHs, whereas the orangutan locus has just three functional genes, oGH-N, oGH-V and oCSH-B, plus a pseudogene, oCSH-L. Analysis of regulatory sequences, including promoter, enhancer and P-elements, shows significant variation; in particular the proximal Pit-1 element of GH-V genes differs markedly from that of other genes in the cluster. Phylogenetic analysis shows that the initial gene duplication led to distinct GH-like and CSH-like genes and that a second duplication provided separate GH-N and GH-V. However, evolution of the CSH-like genes remains unclear. Rapid adaptive evolution gave rise to the distinct CSHs, after the first duplication, and to GH-V after the second duplication. Analysis of transcriptomic databases derived from gorilla tissues establishes that the gGH-N, gGH-V and several gCSH genes are expressed, but the significance of the many CSH genes in gorilla remains unclear. PMID- 27376727 TI - Preface. PMID- 27376726 TI - Toward a Method for Exposing and Elucidating Ethical Issues with Human Cognitive Enhancement Technologies. AB - To develop a method for exposing and elucidating ethical issues with human cognitive enhancement (HCE). The intended use of the method is to support and facilitate open and transparent deliberation and decision making with respect to this emerging technology with great potential formative implications for individuals and society. Literature search to identify relevant approaches. Conventional content analysis of the identified papers and methods in order to assess their suitability for assessing HCE according to four selection criteria. Method development. Amendment after pilot testing on smart-glasses. Based on three existing approaches in health technology assessment a method for exposing and elucidating ethical issues in the assessment of HCE technologies was developed. Based on a pilot test for smart-glasses, the method was amended. The method consists of six steps and a guiding list of 43 questions. A method for exposing and elucidating ethical issues in the assessment of HCE was developed. The method provides the ground work for context specific ethical assessment and analysis. Widespread use, amendments, and further developments of the method are encouraged. PMID- 27376728 TI - Lactobacillus salivarius reverse diabetes-induced intestinal defense impairment in mice through non-defensin protein. AB - Altered intestinal microbiota and subsequent endotoxemia play pathogenic roles in diabetes. We aimed to study the mechanisms of intestinal defense impairment in type 1 diabetes and the effects of Lactobacillus salivarius as well as fructooligosaccharides (FOS) supplementation on diabetes-induced bacterial translocation. Alterations in the enteric microbiome, expression of mucosal antibacterial proteins and bacteria-killing activity of the intestinal mucosa in streptozotocin (STZ)-induced diabetic mice and Ins2(Akita) mice were investigated. The effects of dead L. salivarius (2*10(8)CFU/ml) and FOS (250 mg per day) supplementation for 1 week on endotoxin levels and Klebsiella pneumoniae translocation were also examined. Finally, germ-free mice were cohoused with wild type or Ins2(Akita) mice for 2 weeks to examine the contribution of microbiota on the antibacterial protein expression. STZ-induced diabetic mice developed intestinal defense impairment as demonstrated by decreased mucosal bacteria killing activity; reduction of non-defensin family proteins, such as Reg3beta, Reg3gamma, CRP-ductin and RELMbeta, but not the defensin family proteins; and increased bacterial translocation. Intestinal bacteria overgrowth, enteric dysbiosis and increased intestinal bacterial translocation, particularly pathogenic K. pneumoniae in STZ-induced diabetic mice and Ins2(Akita) mice, were noted. Treating diabetic mice with dead L. salivarius or FOS reversed enteric dysbiosis, restored mucosal antibacterial protein and lessened endotoxin levels as well as K. pneumoniae translocation. Moreover, germ-free mice cohoused with wild-type mice demonstrated more intestinal Reg3beta and RELMbeta expression than those cohoused with Ins2(Akita) mice. These results indicate that hyperglycemia induces enteric dysbiosis, reduction of non-defensin proteins as well as bacteria killing activity of the intestinal mucosa and intestinal defense impairment. Reversal of enteric dysbiosis with dead L. salivarius or FOS supplementation decreases diabetes-induced K. pneumoniae translocation and endotoxin levels through the induction of non-defensin proteins. PMID- 27376724 TI - Kinetochore assembly and function through the cell cycle. AB - The kinetochore is an essential structure for the chromosome segregation machinery in eukaryotes; it serves as a bridge between the spindle microtubules and chromosomes. The kinetochore consists of multiple interconnecting components on the centromere; therefore, understanding its formation, molecular function, and regulation has remained an ongoing challenge. Recent studies have provided new insights into centromere identity, kinetochore assembly, and function. In this review, we discuss recent advances in our understanding of the function and regulation of key kinetochore components. We highlight the reciprocal localization dependencies of the different sub-complexes of the kinetochore and describe their regulation during the cell cycle. PMID- 27376729 TI - Pharmacodynamic assessment of apremilast for the treatment of moderate-to-severe plaque psoriasis. AB - INTRODUCTION: Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the population. Certain systemic drugs currently available for its treatment could be associated, in the long term, with organ toxicity and adverse events, thus, clinical monitoring throughout treatment is required. Moreover, tolerability issues, parenteral administration, and barriers to patient access, such as high cost and specialist management lead to treatment failure. AREAS COVERED: Apremilast is an oral small molecule inhibitor of phosphodiesterase 4 (PDE4i). PDE is the major enzyme class responsible for the hydrolysis of cyclic adenosine monophosphate in immune cells (cAMP). With PDE4 inhibition, apremilast works intracellularly to modulate pro-inflammatory and anti-inflammatory mediator production critically involved in psoriasis. The aim of this paper is to focus the attention on apremilast pharmacodynamics effects, its efficacy and safety in treating moderate-to-severe plaque psoriasis. EXPERT OPINION: Apremilast is an effective and well-tolerated option in treating moderate-to-severe plaque psoriasis. Its safety profile and the oral administration offer significant advantages in prescribing apremilast for the treatment of psoriasis, particularly in some subsets of patients. PMID- 27376731 TI - The Working Modules of Long Noncoding RNAs in Cancer Cells. AB - It is clear that RNA is more than just a messenger between gene and protein. The mammalian genome is pervasively transcribed, giving rise to tens of thousands of noncoding transcripts, especially long noncoding RNAs (lncRNAs). Whether all of these large transcripts are functional remains to be elucidated, but it is evident that there are many lncRNAs that seem not to be the "noise" of the transcriptome. Recent studies have set out to decode the regulatory role and functional diversity of lncRNAs in human physiological and pathological processes, and accumulating evidence suggests that most of the functional lncRNAs achieve their biological functions by controlling gene expression. In this chapter, we will organize these studies to provide a detailed description of the involvement of lncRNAs in the major steps of gene expression that include epigenetic regulation, RNA transcription, posttranscriptional RNA processing, protein translation, and posttranslational protein modification and highlight the molecular mechanisms through which lncRNAs function, involving the interactions between lncRNAs and other biological macromolecules. PMID- 27376730 TI - Noncoding RNAs: New Players in Cancers. AB - The world of noncoding RNAs (ncRNAs) has gained widespread attention in recent years due to their novel and crucial potency of biological regulation. Noncoding RNAs play essential regulatory roles in a broad range of developmental processes and diseases, notably human cancers. Regulatory ncRNAs represent multiple levels of structurally and functionally distinct RNAs, including the best-known microRNAs (miRNAs), the complicated long ncRNAs (lncRNAs), and the newly identified circular RNAs (circRNAs). However, the mechanisms by which they act remain elusive. In this chapter, we will review the current knowledge of the ncRNA field, discussing the genomic context, biological functions, and mechanisms of action of miRNAs, lncRNAs, and circRNAs. We also highlight the implications of the biogenesis and gene expression dysregulation of different ncRNA subtypes in the initiation and development of human malignancies. PMID- 27376732 TI - Methods to Study Long Noncoding RNA Biology in Cancer. AB - Thousands of long noncoding RNAs (lncRNAs) have been discovered in recent years. The functions of lncRNAs range broadly from regulating chromatin structure and gene expression in the nucleus to controlling messenger RNA (mRNA) processing, mRNA posttranscriptional regulation, cellular signaling, and protein activity in the cytoplasm. Experimental and computational techniques have been developed to characterize lncRNAs in high-throughput scale, to study the lncRNA function in vitro and in vivo, to map lncRNA binding sites on the genome, and to capture lncRNA-protein interactions with the identification of lncRNA-binding partners, binding sites, and interaction determinants. In this chapter, we will discuss these technologies and their applications in decoding the functions of lncRNAs. Understanding these techniques including their advantages and disadvantages and developing them in the future will be essential to elaborate the roles of lncRNAs in cancer and other diseases. PMID- 27376733 TI - Relationship Between Noncoding RNA Dysregulation and Epigenetic Mechanisms in Cancer. AB - Epigenetic alterations, including aberrant DNA methylation and histone modification, play key roles in the dysregulation of tumor-related genes, thereby affecting numerous cellular processes, including cell proliferation, cell adhesion, apoptosis, and metastasis. In recent years, studies have demonstrated that short and long noncoding RNAs (ncRNAs) are key players in the initiation and progression of cancer, and epigenetic mechanisms are deeply involved in their dysregulation. Indeed, the growing list of microRNA (miRNA) genes aberrantly methylated in cancer suggests that a large number of miRNAs act as tumor suppressors or oncogenes. In addition, emerging evidence suggests that dysregulation of long ncRNAs (lncRNAs) plays critical roles in tumorigenesis. And because ncRNAs are involved in regulating gene expression through interaction with epigenetic modifiers, their dysregulation appears causally related to epigenetic alterations in cancer. Dissection of the interrelationships between ncRNAs and epigenetic alterations has the potential to reveal novel approaches to the diagnosis and treatment of cancer. PMID- 27376734 TI - Noncoding RNAs in Growth and Death of Cancer Cells. AB - The mammalian genomes are mostly comprised of noncoding genes. And mammalian genomes are characterized by pervasive expression of different types of noncoding RNAs (ncRNAs). In sharp contrast to previous collections, these ncRNAs show strong purifying selection evolutionary conservation. Previous studies indicated that only a small fraction of the mammalian genome codes for messenger RNAs destined to be translated into peptides or proteins, and it is generally assumed that a large portion of transcribed sequences-including pseudogenes and several classes of ncRNAs-do not give rise to peptides or proteins. However, ribosome profiling suggests that ribosomes occupy many regions of the transcriptome thought to be noncoding. Moreover, these observations highlight a potentially large and complex set of biologically regulated translational events from transcripts formerly thought to lack coding potential. Furthermore, accumulating evidence from previous studies has suggested that the novel translation products exhibit temporal regulation similar to that of proteins known to be involved in many biological activity processes. In this review, we focus on the coding potential of noncoding genes and ncRNAs. We also sketched the possible mechanisms for their coding activities. Overall, our review provides new insights into the word of central dogma and is an expansive resource of functional annotations for biomedical research. At last, the outcome of the majority of the translation events and their potential biological purpose remain an intriguing topic for future investigation. PMID- 27376735 TI - Noncoding RNAs in Cancer Cell Plasticity. AB - Accumulating evidence has shown the presence of cancer stem cells in a wide spectrum of human cancers, which have the ability to self-renew and differentiate, thus leading to tumorigenesis, proliferation, cancer dissemination, drug resistance, and tumor relapse. Cancer cell plasticity allows tumor to invade and grow at primary or distant sites. Epithelial-mesenchymal transition (EMT) is the most important mechanism of cancer cell plasticity and cancer stem cells. Substantial evidence has supported a noncoding RNA network, especially miRNA, in regulating cancer cell plasticity and cancer stem cell biology. Besides, lncRNA is also found to participate in cancer development. Understanding the mechanisms of these processes might be valuable for developing accurate targeted therapies to tackle cancer progression and cancer stem cells. PMID- 27376736 TI - Noncoding RNAs in Regulation of Cancer Metabolic Reprogramming. AB - Since the description of the Warburg effect 90 years ago, metabolic reprogramming has been gradually recognized as a major hallmark of cancer cells. Mounting evidence now indicates that cancer is a kind of metabolic disease, quite distinct from conventional perception. While metabolic alterations in cancer cells have been extensively observed in glucose, lipid, and amino acid metabolisms, its underlying regulatory mechanisms are still poorly understood. Noncoding RNA, also known as the "dark matter in life," functions through various mechanisms at RNA level regulating different biological pathways. The last two decades have witnessed the booming of noncoding RNA study on microRNA (miRNA), long noncoding RNA (lncRNA), circular RNA (circRNA), PIWI-interacting RNA (piRNA), etc. In this chapter, we will discuss the regulatory roles of noncoding RNAs on cancer metabolism. PMID- 27376737 TI - Noncoding RNAs in Tumor Angiogenesis. AB - Solid tumors require angiogenesis to grow beyond 2 mm in size. In most cases, tumor cells undergo angiogenic switch and secrete substances that are required for generation of new capillary sprouting from existing blood vessels. Tumor angiogenesis is driven by a complex interplay between pro-angiogenic (VEGF/VEGFR, PDGF/PDGFR) and anti-angiogenic factors (TSP-1/TSP-2) within the tumor microenvironment. In addition, control of tissue remodeling and degradation by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) contribute to tumor angiogenesis. Furthermore, tumor suppressors or oncogenes that control cellular motility and maintain or promote hypoxia (HIFs and MYC) are also actively playing roles in tumor angiogenesis. Noncoding RNAs (ncRNAs), including microRNAs, are a novel class of regulatory molecules that control the gene expression in a posttranscriptional manner. MicroRNAs regulate important physiological processes, such as proliferation, apoptosis, and differentiation, as well as pathological conditions including oncogenesis. Accumulating evidence suggests that microRNAs directly modulate the process of angiogenesis by targeting important angiogenic factors and signaling molecules. Understanding the molecular mechanism behind the regulation of angiogenesis by microRNAs is important due to their therapeutic potential which may lead to improving outcome for cancer patients. Besides, ncRNAs with a regulatory role in angiogenesis, such as long noncoding RNAs (lncRNAs), have been identified in the genome. However, the mechanisms of the vast majority of lncRNAs are currently unknown. For the few lncRNAs characterized at the functional level, accumulating evidence shows that they play important roles in malignant diseases. The function and mechanism in angiogenesis will be described in this chapter. PMID- 27376738 TI - Noncoding RNAs in Cancer Immunology. AB - Cancer immunology is the study of interaction between cancer cells and immune system by the application of immunology principle and theory. With the recent approval of several new drugs targeting immune checkpoints in cancer, cancer immunology has become a very attractive field of research and is thought to be the new hope to conquer cancer. This chapter introduces the aberrant expression and function of noncoding RNAs, mainly microRNAs and long noncoding RNAs, in tumor-infiltrating immune cells, and their significance in tumor immunity. It also illustrates how noncoding RNAs are shuttled between tumor cells and immune cells in tumor microenvironments via exosomes or other microvesicles to modulate tumor immunity. PMID- 27376739 TI - Noncoding RNAs in Therapeutic Resistance of Cancer. AB - Despite the encouraging advances made to date in cancer therapy, the benefits to patients are frequently offset by the development of resistance to therapeutics. Given their involvement in regulating multiple aspects of gene expression and cell signaling that dictates the behaviors of malignant cells, it is not surprising that noncoding RNAs (ncRNAs) play pivotal roles in the resistance of cancers to clinically available therapeutics. Aberrant expression of these ncRNAs, attributed to inherent defects or stress-responsive variations, mediates cellular signaling that compensates for unfavorable molecular events elicited by the therapeutics, thereby preventing the pharmaceuticals from exerting their desired effects on their cellular targets; alternatively, ncRNAs may regulate cancer therapeutic sensitivity by affecting drug accessibility to neoplastic cells and in vivo drug metabolism. In addition, dysregulation of ncRNA expression in cancer stromal cells can impair the responsiveness of neoplastic cells to appropriate therapies. In this chapter, we will describe ncRNA-related mechanisms underlying cancer resistance to routine therapeutics, hopefully providing rationales for the development of drug-sensitizing strategies targeted against or based on these ncRNAs. PMID- 27376740 TI - Noncoding RNAs Regulating Cancer Signaling Network. AB - The cellular signaling network plays a fundamental role during development and disease, especially cancer progression. By deregulating signaling pathways, cancer cells acquire hallmarks of the disease including uncontrolled proliferation, evasion from cell death, activation of angiogenesis, invasion, and metastasis. Noncoding RNAs make substantial contributions to regulating signal transduction in cancer, thereby promoting or suppressing different biological processes during tumorigenesis. This chapter provides an overview on the regulatory functions of noncoding RNAs in the signaling network in cancer cells. It summarizes examples of noncoding RNAs that act as oncogenes or tumor suppressing genes involved in key signal pathways as well as signal crosstalk in cancer cells. PMID- 27376741 TI - Noncoding RNAs Regulating NF-kappaB Signaling. AB - As transcription factors that regulate expression of a variety of genes essential for diverse physiological and pathological processes, nuclear factor kappa B (NF kappaB) family molecules play important roles in the development and progression of malignant tumor, and constitutive activation of NF-kappaB has been evidenced in various types of tumor tissues. Underlying its pathologic role, deregulated expression and/or transactivating activity of NF-kappaB usually involves multiple layers of molecular mechanisms. Noncoding RNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are known to modulate expression and biological functions of regulatory proteins in a variety of cancer contexts. In this chapter, the regulatory role of miRNAs and lncRNAs in NF-kappaB signaling in malignant diseases will be discussed. PMID- 27376742 TI - Noncoding RNAs Regulating p53 and c-Myc Signaling. AB - p53 is one of the most important tumor suppressors and is known to play critical roles in the process of tumor development. Similarly, as an important proto oncogenes, c-Myc is activated in over half of human cancers. Both p53 and c-Myc participate in almost every crucial decision of almost every cell. Therefore, it is utmost important to gain a better understanding of how they affect multiple cellular processes. The physiological and pathologic patterns of p53 and c-Myc regulations are modulated by a large number of cis-elements and transfactors (RNAs and proteins). These elements and factors are composed of a complicated network of intracellular and extracellular pathways. How the noncoding RNAs are involved in their regulations has not been comprehensively reviewed. In this chapter, we will list and describe recently published important noncoding RNAs including microRNAs and long noncoding RNAs, which act as effectors and regulators for both p53 and c-Myc regulation. The purpose of this chapter is to provide a recent progress of noncoding RNA in the regulation of p53 and c-Myc on network of cellular signaling and its potential implications in both basic science and clinical application. PMID- 27376743 TI - Viral Noncoding RNAs in Cancer Biology. AB - Over 12 % of all human cancers are caused by oncoviruses, primarily including Epstein-Barr virus (EBV), high-risk human papillomaviruses (HPVs), hepatitis B and C viruses (HBV and HCV, respectively), and Kaposi's sarcoma herpesvirus (KSHV). In addition to viral oncoproteins, a variety of noncoding RNAs (ncRNAs) produced by oncoviruses have been recognized as important cofactors that contribute to the oncogenic events. In this chapter, we will focus on the recent understanding of the long and short noncoding RNAs, as well as microRNAs of the viruses, and discuss their roles in the biology of multistep oncogenesis mediated by established human oncoviruses. PMID- 27376744 TI - Noncoding RNAs in Cancer Diagnosis. AB - The accuracy and efficiency of tumor treatment depends mainly on early and precise diagnosis. Although histopathology is always the gold standard for cancer diagnosis, noninvasive biomarkers represent an opportunity for early detection and molecular staging of cancer. Besides the classical tumor markers, noncoding RNAs (ncRNAs) emerge to be a novel category of biomarker for cancer diagnosis since the dysregulation of ncRNAs is closely associated with the development and progression of human cancers such as liver, lung, breast, gastric, and other kinds of cancers. In this chapter, we will summarize the different types of ncRNAs in the diagnosis of major human cancers. In addition, we will introduce the recent advances in the detection and applications of circulating serum or plasma ncRNAs and non-blood fluid ncRNAs because the noninvasive body fluid-based assays are easy to examine for cancer diagnosis and monitoring. PMID- 27376745 TI - Therapeutic Potentials of Noncoding RNAs: Targeted Delivery of ncRNAs in Cancer Cells. AB - Knowledge of multiple actions of short noncoding RNAs (ncRNAs) has truly allowed for viewing DNA, RNA, and protein in novel ways. The ncRNAs are an attractive new class of therapeutics, especially against undruggable targets for the treatment of cancer and other diseases. Despite the potential of ncRNAs in cancer therapy, many challenges remain, including rapid degradation and clearance, poor cellular uptake, off-target effects, and immunogenicity. Rational design, chemical modifications, and delivery carriers offer significant opportunities to overcome these challenges. In this chapter, the development of ncRNAs as cancer therapeutics from early stages to clinical trials and strategies for ncRNA targeted delivery to cancer cells will be introduced. PMID- 27376746 TI - Lung protective properties of the volatile anesthetics. PMID- 27376747 TI - Ring opening of epoxides with C-nucleophiles. AB - Ring opening of epoxides has been an area of interest for organic chemists, owing to their reactivity toward nucleophiles. Such reactions yield important products depending on the type of nucleophiles used. This review article covers the synthetic approaches (1991-2015) used for the ring opening of epoxides via carbon nucleophiles. PMID- 27376748 TI - Electrochemical regeneration of phenol-saturated activated carbon - proposal of a reactor. AB - An electrochemical process was used to investigate the activated carbon regeneration efficiency (RE) saturated with aromatics. For this purpose, an electrochemical reactor was developed and the operational conditions of this equipment were investigated, which is applied in activated carbon regeneration process. The influence of regeneration parameters such as processing time, the current used, the polarity and the processing fluid (electrolyte) were studied. The performance of electrochemical regeneration was evaluated by adsorption tests, using phenol as adsorbate. The increase in current applied and the process time was found to enhance the RE. Another aspect that indicated a better reactor performance was the type of electrolyte used, showing best results for NaCl. The polarity showed the highest influence on the process, when the cathodic regeneration was more efficient. The electrochemical regeneration process developed in this study presented regeneration capacities greater than 100% when the best process conditions were used, showing that this form of regeneration for activated carbon saturated with aromatics is very promising. PMID- 27376749 TI - Psychometric properties of WLEIS as a measure of emotional intelligence in the Portuguese and Spanish medical students. AB - The psychometric properties of Wong and Law's (2002) Emotional Intelligence Scale (WLEIS) were analyzed. Participants were 954 medical students: 481 from the University of Extremadura (Spain) and 473 from the University of Lisbon (Portugal). Following Messicks' validation framework, we analyzed the scale's response process, internal structure and relationship with other variables (i.e., engagement). Descriptive statistics, scale reliability, item characteristics, and exploratory and confirmatory analyses supported the distribution of the sixteen items across four factors. Convergent validity analyzed through the rhovc (eta) index showed that all the factors were in the 50% criterion. The factors shared, on average, 23% of the variance showing adequate discriminant validity. Furthermore, the correlations among EI dimensions and engagement were all positive and significant. Overall, the WLEIS demonstrated good psychometric properties. Thus, this study ensures that WLEIS is a valid instrument in Portugal and Spain to evaluate EI in medical students. PMID- 27376750 TI - Studying the teaching of kindness: A conceptual model for evaluating kindness education programs in schools. AB - Recent research suggests that school-based kindness education programs may benefit the learning and social-emotional development of youth and may improve school climate and school safety outcomes. However, how and to what extent kindness education programming influences positive outcomes in schools is poorly understood, and such programs are difficult to evaluate in the absence of a conceptual model for studying their effectiveness. In partnership with Kind Campus, a widely adopted school-based kindness education program that uses a bottom-up program framework, a methodology called concept mapping was used to develop a conceptual model for evaluating school-based kindness education programs from the input of 123 middle school students and approximately 150 educators, school professionals, and academic scholars. From the basis of this model, recommendations for processes and outcomes that would be useful to assess in evaluations of kindness education programs are made, and areas where additional instrument development may be necessary are highlighted. The utility of the concept mapping method as an initial step in evaluating other grassroots or non-traditional educational programming is also discussed. PMID- 27376751 TI - [Pruritus in psoriasis : Profile and therapy]. AB - Psoriasis is a common chronic inflammatory disease with an incidence of about 0.5 3 %. Previously psoriasis was not primarily regarded to be associated with pruritus; however, this perception has changed in recent years. Meanwhile data conclusively show that between 64 and 97 % of patients report about pruritus that can be severe in a number of cases. Apart from suffering from psoriasis, the presence of pruritus causes additional stress and leads to a significant impairment of health-related quality of life. Neurogenic inflammation at least in part contributes to the development of pruritus in psoriasis skin lesions. A number of neuropeptides including substance P and calcitonin gene related peptide can act as pro-inflammatory mediators. There is evidence for a dysbalance between kappa- and u-opioid receptors in lesional skin favoring inflammation and pruritus. After clearing of psoriasis lesions, pruritus is relieved as well. Therefore, specific treatment of pruritus is not necessary in general. In cases where severe pruritus is a prominent symptom, targeted therapy with mirtazapin or doxepin or neuroleptic compounds such as pregabalin or gabapentin or drugs affecting the kappa- und u-opioid receptor balance can be administered. Today the importance of pruritus as a prominent symptom of psoriasis lesions has been widely accepted. In recent and running clinical trials with new drugs, pruritus at baseline and the effect of these drugs on pruritus is always assessed. This awareness also fuels basic research about pruritus in psoriasis. PMID- 27376752 TI - [Pruritus in systemic diseases : Common and rare etiologies]. AB - Chronic pruritus is a symptom of various internal disorders. In contrast to dermatological diseases, pruritus does not present with primary skin alterations in these patients. However, intense scratching may cause secondary skin changes such as abrasion, excoriation, prurigo nodularis, or in rare cases even scaring. The most common internal medicine causes for chronic pruritus are chronic kidney disease, hepatobiliary and hematological disorders as well as adverse drug reactions. Pruritus is less commonly seen in patients with endocrine or metabolic diseases, malabsorption syndromes, infectious diseases and solid tumors. The pathogenesis of pruritus in these disorders remains largely elusive, albeit preliminary insights have been gained for uremic and cholestatic pruritus. Antipruritic treatment is therefore symptomatic in most cases and may represent a clinical challenge. The calcium channel blockers gabapentin and pregabalin have the best proven efficacy in chronic kidney disease-associated pruritus. In Japan nalfurafine, a kappa-opioid receptor agonist, has been licensed for this indication. UVB light may also attenuate uremic symptoms. In patients suffering from hepatobiliary disorders the sequestrant cholestyramine and the enzyme inducer rifampicin are effective. Furthermore, MU-opioid receptor antagonists and sertraline may be used to ameliorate cholestatic pruritus. So far, no randomized controlled trials have been performed for chronic itch in other internal medicine disorders. Antipruritic treatment is mainly based on effective therapy of the underlying disease. PMID- 27376753 TI - Transient Retinal Dysfunctions after Acute Cannabis Use. AB - Although cannabis is very widespread worldwide, the impact of cannabis on visual function remains poorly understood. This is partly due to numerous difficulties met in developing clinical studies in cannabis users. Here, we report the first documented case of neuroretinal dysfunction after acute cannabis smoking. This observation was favored by the need of an annual ophthalmic evaluation in the context of a chloroquine intake for a systemic lupus erythematosus in a 47-year old heavy cannabis user. A complete ophthalmic evaluation including visual acuity tests, intraocular pressure, fundoscopic examination, automated 10 degrees central visual field, full-field electroretinogram (ERG) and multifocal ERG was performed twice - 30 min and 5 h after cannabis smoking. A strong decrease (up to 48%) in the a-wave amplitude of the full-field ERG was measured 30 min after cannabis smoking for all scotopic responses compared with the responses 5 h after smoking. Other tests showed reproducible results between the 2 series of measurements. This clinical case suggests that acute inhalation of cannabis affects the photoreceptors functioning. This rare situation suggests further investigations are required on the impact of cannabis on retinal processing, especially since cannabis has been incriminated in car injuries. PMID- 27376755 TI - Exploring women's sensory experiences of undergoing colposcopy and related procedures: implications for preparatory sensory information provision. AB - INTRODUCTION: Some women experience distress during colposcopy examinations which is partly related to women's fear, or experience, of pain during the procedure. However, little is known about women's sensory experiences of colposcopy (other than pain) or what might impact on these experiences. The aim of this study was to explore women's sensory experiences of colposcopy and related procedures and identify factors which influenced negative sensory experiences. METHODS: In-depth interviews were conducted with 23 women who had undergone, for the first time, a colposcopy (some with related procedures, including punch biopsies and loop excision) as part of follow-up for abnormal cervical cytology. Interviews were analysed thematically using the Framework Approach to organise the data and identify emerging higher-order themes. RESULTS: Women described a range of sensory experiences including pain or discomfort, cramping, stinging and cold sensations (due to the application of acetic acid to the cervix). Four key themes emerged as important aspects of the overall sensory experience: levels of pain, treatment-specific sensations, anaesthetic-specific sensations and solution specific sensations. Factors that may influence women having a negative sensory experience were sensory expectations of the procedure(s) and lack of preparatory sensory information. DISCUSSION: Our study provides unique in-depth insight into women's sensory experiences of colposcopy and related procedures and suggests women require more preparatory sensory information. The issues identified as contributing to women having a negative sensory experience may help inform the development of pre-colposcopy information which may better prepare women with abnormal cervical cytology for follow-up examinations. PMID- 27376754 TI - Voriconazole-induced periostitis: a new rheumatic disorder. AB - Over the past few years, several reports of periostitis affecting patients treated with voriconazole appeared in the literature. As rheumatologists are likely to be called to see such patients, a review of the reported cases was undertaken. A systematic search of Pubmed and Google scholar for case reports, case series and observational studies was undertaken. Twenty-six articles including 23 case reports/case series (total 40 patients), a prospective study and two retrospective studies of 58 cases were included. Age ranged from 3 months to 77 years. Eleven cases (27.5 %) were male and 29 cases (72.5 %) were female. The duration of treatment varied from 6 weeks to 8 years (mean 53.6, SD 77.4 weeks). Most cases presented with diffuse skeletal pain affecting various sites in association with elevated alkaline phosphatase. Periostitis is increasingly reported and should be considered in patients taking voriconazole who present with bone pain and/or alkaline phosphatase elevation. PMID- 27376756 TI - Parasites of freshwater fishes and the Great American Biotic Interchange: a bridge too far? AB - We examine the extent to which adult helminths of freshwater fishes have been part of the Great American Biotic Interchange (GABI), by integrating information in published studies and new data from Panama with fish biogeography and Earth history of Middle America. The review illustrates the following: (1) the helminth fauna south of the Trans-Mexican Volcanic Belt, and especially south of the Isthmus of Tehuantepec, shows strong Neotropical affinities; (2) host-parasite associations follow principles of the 'biogeographic core fauna' in which host lineage specificity is pronounced; (3) phylogenetic analysis of the widespread freshwater trematode family Allocreadiidae reveals a complex history of host shifting and co-diversification involving mainly cyprinodontiforms and characids; (4) allocreadiids, monogeneans and spiruridan nematodes of Middle American cyprinodontiforms may provide clues to the evolutionary history of their hosts; and (5) phylogenetic analyses of cryptogonimid trematodes may reveal whether or how cichlids interacted with marine or brackish-water environments during their colonization history. The review shows that 'interchange' is limited and asymmetrical, but simple narratives of northward isthmian dispersal will likely prove inadequate to explain the historical biogeography of many host-parasite associations in tropical Middle America, particularly those involving poeciliids. Finally, our study highlights the urgent need for targeted survey work across Middle America, focused sampling in river drainages of Colombia and Venezuela, and deeper strategic sampling in other parts of South America, in order to develop and test robust hypotheses about fish-parasite associations in Middle America. PMID- 27376757 TI - Evaluation by fluorescence, STD-NMR, docking and semi-empirical calculations of the o-NBA photo-acid interaction with BSA. AB - Serum albumins present reversible pH dependent conformational transitions. A sudden laser induced pH-jump is a methodology that can provide new insights on localized protein (un)folding processes that occur within the nanosecond to microsecond time scale. To generate the fast pH jump needed to fast-trigger a protein conformational event, a photo-triggered acid generator as o nitrobenzaldehyde (o-NBA) can be conveniently used. In order to detect potential specific or nonspecific interactions between o-NBA and BSA, we have performed ligand-binding studies using fluorescence spectroscopy, saturation transfer difference (STD) NMR, molecular docking and semi-empirical calculations. Fluorescence quenching indicates the formation of a non-fluorescent complex in the ground-state between the fluorophore and the quencher, but o-NBA does not bind much effectively to the protein (Ka~4.34*10(3)M(-1)) and thus can be considered a relatively weak binder. The corresponding thermodynamic parameters: DeltaG degrees , DeltaS degrees and DeltaH degrees showed that the binding process is spontaneous and entropy driven. Results of (1)H STD-NMR confirm that the photo-acid and BSA interact, and the relative intensities of the signals in the STD spectra show that all o-NBA protons are equally involved in the binding process, which should correspond to a nonspecific interaction. Molecular docking and semi-empirical calculations suggest that the o-NBA binds preferentially to the Trp-212-containing site of BSA (FA7), interacting via hydrogen bonds with Arg 217 and Tyr-149 residues. PMID- 27376758 TI - Raman microspectroscopy of Hematoporphyrins. Imaging of the noncancerous and the cancerous human breast tissues with photosensitizers. AB - Raman microspectroscopy combined with fluorescence were used to study the distribution of Hematoporphyrin (Hp) in noncancerous and cancerous breast tissues. The results demonstrate the ability of Raman spectroscopy to distinguish between noncancerous and cancerous human breast tissue and to identify differences in the distribution and photodegradation of Hematoporphyrin, which is a photosensitizer in photodynamic therapy (PDT), photodynamic diagnosis (PDD) and photoimmunotherapy (PIT) of cancer. Presented results show that Hematoporphyrin level in the noncancerous breast tissue is lower compared to the cancerous one. We have proved also that the Raman intensity of lipids and proteins doesn't change dramatically after laser light irradiation, which indicates that the PDT treatment destroys preferably cancer cells, in which the photosensitizer is accumulated. The specific subcellular localization of photosensitizer for breast tissues samples soaked with Hematoporphyrin was not observed. PMID- 27376759 TI - Effect of low-intensity pure tone auditory stimulation on patients with rapid eye movement sleep behavior disorder. AB - OBJECTIVE: This study aimed to investigate the influence of low-intensity pure tone auditory stimulation on patients with rapid eye movement (REM), sleep behavior disorder (RBD), and attempt to identify a new method of RBD intervention. METHODS: Patients diagnosed with idiopathic RBD (iRBD) or symptomatic RBD (sRBD) were given auditory stimulation of low-intensity pure tones during their REM sleep. Sleep parameters including sleep process, sleep architecture as well as eye movements (EMs) frequency, and amplitude were recorded by polysomnography monitoring at pre-, intra-, and post-stimulation. RESULTS: Thirteen iRBD and 18 sRBD patients completed this study. Auditory stimulation significantly reduced the EMs frequency and amplitude in iRBD and sRBD patients (p < 0.05). In the iRBD group, the intra-stimulated FSL increased significantly than the pre-stimulated FSL (p < 0.05). After stimulation, patients had similar sleep latency (FSL), rapid eye movement sleep latency (RSL) and periodic limb movements in sleep (PLMS) compared with control. In the sRBD group, the intra-stimulated total sleep time, sleep efficiency was significantly increased, whereas the RSL and PLMS were significantly reduced compared with the pre-stimulated ones (all p < 0.05). The sRBD patients had similar time in bed, FSL and RBD episodes compared with control (all p < 0.05) in spite of significant difference before stimulation (all p < 0.05). However, the sleep architecture was not influenced by the stimulation despite the decrease in N3% in iRBD group (p < 0.05). CONCLUSION: Low-intensity pure tone auditory stimulation may be a potentially effective intervention for RBD, especially for sRBD. PMID- 27376760 TI - Alexithymia and psychosocial problems among Italian preadolescents. A latent class analysis approach. AB - The study, conducted on Italian preadolscents aged 11 to 13 belonging to the general population, aims to investigate the relationship between the emotional functioning, namely, alexithymia, and the risk of developing behavioral and emotional problems measured using the Strength and Difficulty Questionnaire. The latent class analysis approach allowed to identify two latent variables, accounting for the internalizing (emotional symptoms and difficulties in emotional awareness) and for the externalizing problems (conduct problems and hyperactivity, problematic relationships with peers, poor prosocial behaviors and externally oriented thinking). The two latent variables featured two latent classes: the difficulty in dealing with problems and the strength to face problems that was representative of most of the healthy participants with specific gender differences. Along with the analysis of psychopathological behaviors, the study of resilience and strengths can prove to be a key step in order to develop valuable preventive approaches to tackle psychiatric disorders. PMID- 27376761 TI - Telomerase, Autophagy and Acute Kidney Injury. AB - In humans, aging is associated with telomere shortening and increased susceptibility to acute kidney injury. Telomerase is essential to maintain telomere length. The fourth generation mice with telomerase deletion have progressive shortening of telomeres. Those mice delayed recovery from ischemia reperfusion injury, due to an increase in tubule cell senescence and impairment of autophagy, the latter of which may be mediated in part by increased mTOR signaling. (c) 2016 S. Karger AG, Basel. PMID- 27376762 TI - The role of food stiffness in dental microwear feature formation. AB - OBJECTIVE: The etiology of dental microwear is incompletely understood, despite copious documentation of wear patterns from wild and captive specimens across numerous vertebrate taxa. Among the contested issues with respect to microwear formation is the question of whether materials softer than enamel (specifically, foods themselves) can produce wear features. DESIGN: We examine the creation of enamel microwear features in vitro from foods that vary in hardness and toughness on a sample of mammalian lower molars (pig, bear, deer, and primate). These experiments involved applying loads at a constant displacement rate perpendicular to an occlusal enamel surface. Changes in surface microwear textures were assessed after 10 loads. RESULTS: Our experiments demonstrate that even relatively soft foods free of exogenous abrasives modify surface texture to produce distinctive microwear fabrics. Consequently, these data provide clear evidence that materials softer than enamel are capable of indenting and abrading enamel surfaces. Foods with a relatively high elastic modulus are associated with larger and more extensive microwear features, although the relationship between food stiffness and rate of microwear formation does not appear to be a simple one. CONCLUSIONS: These observations refute recent arguments that food material is an insignificant agent in the formation and accumulation of enamel microwear. Relative hardness of ingested materials is only one factor in the etiology of microwear formation. PMID- 27376763 TI - Prostate Volume Index Associates with a Decreased Risk of Prostate Cancer: Results of a Large Cohort of Patients Elected to a First Biopsy Set. AB - : Background/Aims/Objectives: In patients elected to the first prostate biopsy set, the risk of prostate cancer (PCA) may be predicted by clinical factors. The aim of this study was to investigate on prostate volume index (PVI), defined as the ratio of volume of the transitional zone to the volume of the peripheral zone, and PCA risk. METHODS: The study retrospectively evaluated 1,327 patients and included only the first biopsy set with 14 cores. PCA risk was assessed by using the multivariate logistic regression model. RESULTS: The analysis evaluated 596 patients. The detection rate of PCA was 49%. Age, prostate specific antigen, PVI and digital rectal exam were independent factors of PCA risk, which was decreased by PVI (OR 0.224; 95% CI 0.157-0.380). The goodness of fit statistics assessed model efficacy. CONCLUSIONS: In a large cohort undergoing the first biopsy set, PVI associated with a decreased risk of PCA. Confirmatory studies are required. PMID- 27376764 TI - Pulsed Laser Deposited Dysprosium-Doped Gadolinium-Vanadate Thin Films for Noncontact, Self-Referencing Luminescence Thermometry. AB - Lanthanide-doped vanadate thin films offer (i) a promising platform for luminescence-based noncontact temperature sensing; (ii) ratiometric/self referencing absolute measurements; (iii) exceptional repeatability and reversibility for multirun uses and a long life cycle; (iv) 2% K(-1) maximum temperature sensitivity (among the highest recorded for inorganic nanothermometers); (v) a temperature resolution greater than 0.5 K; and (vi) the potential for high-resolution 2D temperature mapping. PMID- 27376765 TI - Multilaminar networks of cortical neurons integrate common inputs from sensory thalamus. AB - Neurons in the thalamorecipient layers of sensory cortices integrate thalamic and recurrent cortical input. Cortical neurons form fine-scale, functionally cotuned networks, but whether interconnected cortical neurons within a column process common thalamocortical inputs is unknown. We tested how local and thalamocortical connectivity relate to each other by analyzing cofluctuations of evoked responses in cortical neurons after photostimulation of thalamocortical axons. We found that connected pairs of pyramidal neurons in layer (L) 4 of mouse visual cortex share more inputs from the dorsal lateral geniculate nucleus than nonconnected pairs. Vertically aligned connected pairs of L4 and L2/3 neurons were also preferentially contacted by the same thalamocortical axons. Our results provide a circuit mechanism for the observed amplification of sensory responses by L4 circuits. They also show that sensory information is concurrently processed in L4 and L2/3 by columnar networks of interconnected neurons contacted by the same thalamocortical axons. PMID- 27376766 TI - Illuminating current pitfalls in optimal photobiomodulation device development and assessment for treating hair loss. PMID- 27376767 TI - Anakinra Protects Against Serum Deprivation-Induced Inflammation and Functional Derangement in Islets Isolated From Nonhuman Primates. AB - We investigated whether serum deprivation induces islet amyloid polypeptide (IAPP) oligomer accumulation and/or a proinflammatory response and, if so, whether the addition of interleukin (IL)-1 receptor antagonist to the culture medium can relieve the proinflammatory response during serum-deprived culture of nonhuman primate (NHP) islets. After culture in medium with and without Ana under serum-deprived culture conditions, IAPP oligomer/amyloid accumulation, in vitro viability, islet function, cytokine secretion, and posttransplantation outcome in streptozotocin-induced diabetic nude mice were determined in islets isolated from heterozygote human IAPP transgenic (hIAPP+/- ) mice and/or NHP islets. Serum deprivation induced accumulation of IAPP oligomer, but not amyloid, in NHP islets. Anakinra (Ana) protected islets from the serum deprivation-induced impairment of in vitro viability and glucose-stimulated insulin secretion and attenuated serum deprivation-induced caspase-1 activation, transcription, and secretion of IL-1beta, IL-6, and tumor necrosis factor-alpha in hIAPP+/- mice and NHP islets. Supplementation of medium with Ana during serum-deprived culture also improved posttransplantation in vivo outcomes of NHP islets. In conclusion, serum deprivation induced accumulation of IAPP oligomers and proinflammatory responses in cultured isolated islets. Supplementation of the culture medium with Ana attenuated the functional impairment and proinflammatory responses induced by serum deprivation in ex vivo culture of NHP islets. PMID- 27376768 TI - UMI-4C for quantitative and targeted chromosomal contact profiling. AB - We developed a targeted chromosome conformation capture (4C) approach that uses unique molecular identifiers (UMIs) to derive high-complexity quantitative chromosome contact profiles with controlled signal-to-noise ratios. UMI-4C detects chromosomal interactions with improved sensitivity and specificity, and it can easily be multiplexed to allow robust comparison of contact distributions between loci and conditions. This approach may open the way to the incorporation of contact distributions into quantitative models of gene regulation. PMID- 27376769 TI - m(6)A-LAIC-seq reveals the census and complexity of the m(6)A epitranscriptome. AB - N(6)-Methyladenosine (m(6)A) is a widespread, reversible chemical modification of RNA molecules, implicated in many aspects of RNA metabolism. Little quantitative information exists as to either how many transcript copies of particular genes are m(6)A modified ('m(6)A levels') or the relationship of m(6)A modification(s) to alternative RNA isoforms. To deconvolute the m(6)A epitranscriptome, we developed m(6)A-level and isoform-characterization sequencing (m(6)A-LAIC-seq). We found that cells exhibit a broad range of nonstoichiometric m(6)A levels with cell-type specificity. At the level of isoform characterization, we discovered widespread differences in the use of tandem alternative polyadenylation (APA) sites by methylated and nonmethylated transcript isoforms of individual genes. Strikingly, there is a strong bias for methylated transcripts to be coupled with proximal APA sites, resulting in shortened 3' untranslated regions, while nonmethylated transcript isoforms tend to use distal APA sites. m(6)A-LAIC-seq yields a new perspective on transcriptome complexity and links APA usage to m(6)A modifications. PMID- 27376771 TI - Let me take the wheel: Illusory control and sense of agency. AB - Illusory control refers to an effect in games of chance where features associated with skilful situations increase expectancies of success. Past work has operationalized illusory control in terms of subjective ratings or behaviour, with limited consideration of the relationship between these definitions, or the broader construct of agency. This study used a novel card-guessing task in 78 participants to investigate the relationship between subjective and behavioural illusory control. We compared trials in which participants (a) had no opportunity to exercise illusory control, (b) could exercise illusory control for free, or (c) could pay to exercise illusory control. Contingency Judgment and Intentional Binding tasks assessed explicit and implicit sense of agency, respectively. On the card-guessing task, confidence was higher when participants exerted control than in the baseline condition. In a complementary model, participants were more likely to exercise control when their confidence was high, and this effect was accentuated in the pay condition relative to the free condition. Decisions to pay were positively correlated with control ratings on the Contingency Judgment task, but were not significantly related to Intentional Binding. These results establish an association between subjective and behavioural illusory control and locate the construct within the cognitive literature on agency. PMID- 27376770 TI - Nanoscale imaging of RNA with expansion microscopy. AB - The ability to image RNA identity and location with nanoscale precision in intact tissues is of great interest for defining cell types and states in normal and pathological biological settings. Here, we present a strategy for expansion microscopy of RNA. We developed a small-molecule linker that enables RNA to be covalently attached to a swellable polyelectrolyte gel synthesized throughout a biological specimen. Then, postexpansion, fluorescent in situ hybridization (FISH) imaging of RNA can be performed with high yield and specificity as well as single-molecule precision in both cultured cells and intact brain tissue. Expansion FISH (ExFISH) separates RNAs and supports amplification of single molecule signals (i.e., via hybridization chain reaction) as well as multiplexed RNA FISH readout. ExFISH thus enables super-resolution imaging of RNA structure and location with diffraction-limited microscopes in thick specimens, such as intact brain tissue and other tissues of importance to biology and medicine. PMID- 27376772 TI - Intestinal stenosis of Garre: A rare cause of small bowel obstruction in the virgin abdomen. AB - INTRODUCTION: Small bowel obstruction (SBO) in the virgin abdomen usually requires operative intervention. Intestinal stenosis of Garre is a rare and frequently missed cause of SBO following hernia repair. METHODS: We describe a case of intestinal stenosis of Garre and provide a comprehensive review of the literature. Statistical analysis was performed using IBM SPSS Statistics V.22 software and included descriptive analysis. RESULTS: Most males developed a delayed stricture following an inguinal hernia repair (93.3%). 84.6% of females, on the other hand, developed intestinal stenosis following repair of a femoral hernia. 87.5% of strictures developed on the right side. The timing of development of a bowel obstruction is very variable and ranges from 5days to 22 years. 22 patients (68.8%), however, presented with an obstruction within 5 months of hernia repair. CONCLUSIONS: Intestinal stenosis of Garre is an under reported cause of delayed stricture formation.It is most common following right inguinal hernia repair in men and right femoral hernia repair in women. PMID- 27376773 TI - Atypical leg ulcers after sclerotherapy for treatment of varicose veins: Case reports and literature review. AB - INTRODUCTION: Skin necrosis is a rare complication of foam sclerotherapy, a common form of treatment for varicose veins. PRESENTATION OF CASE: Both patients presented to the outpatient clinic within 2-14days after foam sclerotherapy with Aethoxysklerol((r)) 1%, with severe soft tissue and skin necrosis. Further aggressive treatment of the ulcer was required to resolve the necrosis, resulting in marked residual scar and well granulated leg ulcer respectively. DISCUSSION: Foam sclerotherapy is a common and usually well-tolerated treatment modality for varicose veins. The aetiology of skin necrosis is conventionally related to extravasation of sclerosant. In order to minimise the risk of necrosis, the lowest concentration and lowest volume of sclerosant necessary to achieve adequate treatment of the target vein should be used. CONCLUSION: We would like to emphasise that whilst skin and soft tissue necrosis is a rare complication of foam sclerotherapy, it is a complication that is highly disfiguring and requires aggressive treatment. As such, it should be adequately discussed with the patient prior to obtaining informed consent. PMID- 27376774 TI - Herniation through gastrostomy site: Case report. AB - INTRODUCTION: Herniation through gastrostomy site is an extremely rare complication of percutaneous endoscopic gastrostomy (PEG). We present two unusual cases of gastrostomy site herniation, the surgical management thereof, and a corresponding review of the literature. CASE PRESENTATION: The first patient is a 65year old Caucasian male who complained of epigastric pain and a bulge at his previous gastrostomy tube incision site three weeks after its removal. Initial exam revealed a hernia measuring approximately 10cm which was later repaired by laparoscopic surgery with a composite mesh. The second case is 66year old obese Caucasian male who complained of continued pain in the midepigastric region around his gastrostomy site scar five months after removal of his PEG tube. On physical exam he was found to have a hernia of 6cm in the midepigastrium. His hernia was later repaired by open surgery with a composite mesh. Both patients recovered uneventfully postoperatively. CONCLUSION: Herniation through gastrostomy site is a possible complication of PEG tube and clinicians should consider this possibility in patients with ongoing leakage, bulge or pain at the gastrostomy site. This entity can be safely corrected via laparoscopic or open techniques. PMID- 27376776 TI - Proteomic profiling of muscle fibre type shifting in neuromuscular diseases. AB - INTRODUCTION: Mature skeletal muscles are composed of a complex assembly of slow twitching, fast-twitching and hybrid fibres. Since muscle fibres exhibit a high degree of cellular plasticity, changed physiological conditions or pathophysiological disturbances have generally a substantial impact on fibre specification. AREAS COVERED: This article reviews the findings from comparative proteomic profiling studies that have focused on neuromuscular diseases and discusses the identified protein changes of fibre type shifting. The reviewed literature on weight loss, obesity, diabetes, cancer cachexia, disuse atrophy, motor neuron disease, myotonia, inflammatory myopathies, myofibrillar myopathies, muscular dystrophies and sarcopenia of old age suggests that proteome-wide alterations occur in the expression of distinct protein families, encompassing especially contractile and regulatory proteins of the acto-myosin apparatus. Expert commentary: The systematic determination of proteome-wide changes in neuromuscular disorders can now be used to design novel diagnostic and therapy monitoring tools for evaluating fibre transitions in pathological muscles. PMID- 27376775 TI - A rare case of ischaemic pneumatosis intestinalis and hepatic portal venous gas in an elderly patient with good outcome following conservative management. AB - INTRODUCTION: Pneumatosis intestinalis (PI) and hepatic portal venous gas (HPVG) are typically associated and are likely to represent a spectrum of the same disease. The causes of both entities range from benign to life-threatening conditions. Ischaemic causes are known to be fatal without emergency surgical intervention. PRESENTATION OF CASE: In this case a 93year old male experienced acute abdominal pain radiating to his back, with nausea and vomiting and a 2-week history of altered bowel habit. Examination revealed abdominal tenderness and distension. He had deranged white cell count (WCC) and renal function. Computed tomography (CT) revealed PI with associated HPVG. The cause was due to ischaemic pathology. The patient was managed conservatively with antibiotics and was discharged 7days later with resolution of his abdominal pain and WCC. DISCUSSION: The pathogenesis of HPVG secondary to PI is poorly understood but usually indicates intestinal ischaemia, thought to carry a mortality of around 75%. HPVG in the older patient usually necessitates emergency surgery however this is not always in the patient's best interest. CONCLUSION: There are few reported cases of patient survival following conservative management of PI and HPVG secondary to ischaemic pathology. This case demonstrates the possibility of managing this condition without aggressive surgical intervention especially when surgery would likely result in mortality due to frailty and morbidity. Further work is required to identify suitable patients. PMID- 27376777 TI - Alpha plus beta annealed and aged Ti-15 Mo alloy for high strength implant applications. AB - Management of femur fractures requires titanium alloy implants that provide a good combination of static strength and ductility plus sufficient high cycle fatigue strength to resist repetitive loading. A research program was initiated to determine whether aging treatments could increase the strength of alpha + beta Ti-15Mo while maintaining acceptable tensile ductility. A pilot heat treating study indicated the best combination of strength and ductility was obtained using an alpha + beta annealing temperature of 705 degrees C +/- 10 degrees C followed by an aging treatment of 482 degrees C +/- 10 degrees C. EBSD data for four suppliers revealed that the alpha phase ratios ranged from 16.3% to 18.6% and the beta phase ratios ranged from 81.4% to 83.7%. Mean beta grain size diameters ranged between 1.42 and 1.78 um. Tensile testing qualification data from four suppliers was statistically analyzed and reviewed. Minimum reproducible tensile values were established and incorporated into ASTM F2066-13 implant material standard. Cantilever fatigue testing was performed with proximal femoral nail implants that were fabricated into fully finished implant constructs. Fatigue results for 125 degrees , 130 degrees , and 135 degrees implant constructs met the acceptance criteria regarding the fatigue runout load limits and failure modes that were identified. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2010-2018, 2017. PMID- 27376778 TI - Parental responses to youths' reports of teen dating violence: Recommendations from parents and youth. AB - Parental responses to teen dating violence (TDV) can influence children's behaviors. This qualitative study presents findings from focus groups analyzing parental responses to TDV. Thirty-one parents and 55 teens, recruited from local family service agencies located in southwestern part of the country, participated in separate focus groups that presented dating violence scenarios. Focus group results indicated that parents and teens both urge communication that included parents asking questions, educating the teen, sharing their personal experiences, and giving teens advice. Parental and teens' comments also focused on the importance of protecting teens, providing support for teens, refraining from overreacting and offering counseling services. Parents, more than teens, stressed the importance of educating teens; teens, more than parents, stressed the importance of parents supporting and providing comfort to teens while refraining from overreacting and yelling. Implications for programming with parents and future research are included. PMID- 27376779 TI - 10-DHGD ameliorates cisplatin-induced nephrotoxicity in rats. AB - : Organs subjected to chronic injuries may develop tissue fibrosis. Several factors contribute to the combat injurious stimuli to repair, heal and alleviate any disturbance. Secretion of chemokines, migration of inflammatory cells to the affected site and activation of fibroblast for production of extracellular matrix (ECM) are examples. Recently, few studies have delt with 10-dehydrogingerdione (10-DHGD), one of the active constituent of ginger extracts that has been published. This constituent proved to be potent antioxidant, anti-inflammatory, cholesterol ester transfer protein (CETP) inhibitor, indeed, a hypolipemic agent. It has been selected in the present study as a natural anti-inflammatory agent to combat inflammation, nephrotoxicity and renal fibrosis-induced by cisplatin. Renal fibrosis state demonstrated a significant increase in creatinine, urea, nuclear factor kappa (NF-kB), insulin like growth factor I (IGF-I), fibroblast growth factor-23 (FGF-23) along with a significant decrease of hepatocytes growth factor (HGF), renal glutathione (GSH) and in confirm to histopathological examination of kidney tissue. Administration of 10-DHGD orally daily for 4 weeks resulted in a significant improvement of both the biomarkers studied in addition to the histopathological profile of the renal tissues. CONCLUSION: 10-DHGD exhibited a marked anti-inflammatory potential, alleviated to a great extent of nephrotoxicity and renal fibrosis induced by cisplatin. PMID- 27376780 TI - Nm23H1 mediates tumor invasion in esophageal squamous cell carcinoma by regulation of CLDN1 through the AKT signaling. AB - Esophageal cancer is a lethal malignancy worldwide. Previously, low expression of metastasis suppressor Nm23H1 and tight junction (TJ) protein claudin-1 (CLDN1) have been known to correlate with poor prognosis in esophageal squamous cell carcinoma (ESCC). However, the molecular interaction between them has not been clarified. In the present study, we first examined the expression of Nm23H1 and CLDN1 in 74 surgical ESCC samples by immunohistochemistry (IHC) to verify their clinicopathologic significance. The biologic effects of Nm23H1 gene silencing or overexpression in ESCC cell lines were then studied by migration and invasion studies, and its regulation on CLDN1 expression was also investigated by western blot analysis. Moreover, the expression of Nm23H1 and CLDN1 at the same invasion front of ESCC tumors was verified by immunofluorescence. The results showed a significantly positive correlation between the expression of Nm23H1 and CLDN1 (gamma=0.296, P=0.011) in surgical specimens, especially for the 34 tumors with lymph-node metastasis (gamma=0.455, P=0.007). In ESCC cell lines, silencing of Nm23H1 expression markedly enhanced cell invasiveness, accompanied by increased Akt phosphorylation and decreased CLDN1 expression. Conversely, Nm23H1-expressed transfectants exhibited reduced invasiveness, decreased Akt phosphorylation and correspondingly increased CLDN1 expression. Regain of CLDN1 expression in ESCC cells significantly suppressed invasiveness, but did not influence the Akt phosphorylation. Moreover, treating Nm23H1-depleted cells with the AKT inhibitor MK2206 recovered CLDN1 expression, and diminished the invasiveness of ESCC cells. Finally, decreased expressions of both CLDN1 and E-cadherin were observed at the invasive front of the Nm23H1-negative tumors. Overall, our current study documented that reduced Nm23H1 expression activates the AKT signaling pathway, results in diminished CLDN1 expression and potentiates invasiveness of ESCC cells. Enhancement of Nm23H1 expression, inhibition of the AKT signaling pathway, or combined, might be a potential treatment strategy in selective ESCC patients. PMID- 27376781 TI - Petroleum hydrocarbon contamination, plant identity and arbuscular mycorrhizal fungal (AMF) community determine assemblages of the AMF spore-associated microbes. AB - The root-associated microbiome is a key determinant of pollutant degradation, soil nutrient availability and plant biomass productivity, but could not be examined in depth prior to recent advances in high-throughput sequencing. Arbuscular mycorrhizal fungi (AMF) form symbioses with the majority of vascular plants. They are known to enhance mineral uptake and promote plant growth and are postulated to influence the processes involved in phytoremediation. Amplicon sequencing approaches have previously shown that petroleum hydrocarbon pollutant (PHP) concentration strongly influences AMF community structure in in situ phytoremediation experiments. We examined how AMF communities and their spore associated microbiomes were structured within the rhizosphere of three plant species growing spontaneously in three distinct waste decantation basins of a former petrochemical plant. Our results show that the AMF community was only affected by PHP concentrations, while the AMF-associated fungal and bacterial communities were significantly affected by both PHP concentrations and plant species identity. We also found that some AMF taxa were either positively or negatively correlated with some fungal and bacterial groups. Our results suggest that in addition to PHP concentrations and plant species identity, AMF community composition may also shape the community structure of bacteria and fungi associated with AMF spores. PMID- 27376782 TI - Classification of human meningiomas: lights, shadows, and future perspectives. AB - Meningiomas represent the most common primary tumors of the central nervous system (CNS) in adulthood. They are currently classified into several histotypes and into three grades of malignancy according to the criteria of the World Health Organization (WHO) classification of tumors of the CNS. WHO histological grade is currently the most significant morphological predictor of recurrence risk of meningiomas. For this reason, it is fully taken into consideration in postsurgical therapeutic decision making in patients with meningioma. However, the main drawback of the WHO grading system system is that criteria for its assessment are rather subjective and poorly standardized. Hence, additional factors are warranted to predict recurrence risk of meningiomas, so that patients may actually receive the most appropriate therapy. In recent years, biomolecular pathogenesis of meningiomas has been partially clarified, and many efforts have been made in the identification of molecular factors associated with recurrence risk of meningioma. Here we review WHO criteria currently used for classification of meningiomas and discuss on pitfalls and limits of grading assessment. In addition we present the latest advancement in the knowledge of biomolecular alterations involved in the pathogenesis and progression of meningiomas. Similarly to what has already happened for gliomas, a novel classification integrating histology and molecular information might overcome the limits of histological classification in terms of reproducibility as well as of prognostic and predictive relevance. (c) 2016 Wiley Periodicals, Inc. PMID- 27376783 TI - On detector linearity and precision of beam shift detection for quantitative differential phase contrast applications. AB - Differential phase contrast is a STEM imaging mode where minute sideways deflections of the electron probe are monitored, usually by using a position sensitive device (Chapman, 1984 [1]; Lohr et al., 2012 [2]) or, alternatively in some cases, a fast camera (Muller et al., 2012 [3,4]; Yang et al., 2015 [5]; Pennycook et al., 2015 [6]) as a pixelated detector. While traditionally differential phase contrast electron microscopy was mainly focused on investigations of micro-magnetic domain structures and their specific features, such as domain wall widths, etc. (Chapman, 1984 [1]; Chapman et al., 1978, 1981, 1985 [7-9]; Sannomiya et al., 2004 [10]), its usage has recently been extended to mesoscopic (Lohr et al., 2012, 2016 [2,12]; Bauer et al., 2014 [11]; Shibata et al., 2015 [13]) and nano-scale electric fields (Shibata et al., 2012 [14]; Mueller et al., 2014 [15]). In this paper, the various interactions which can cause a beam deflection are reviewed and expanded by two so far undiscussed mechanisms which may be important for biological applications. As differential phase contrast microscopy strongly depends on the ability to detect minute beam deflections we first treat the linearity problem for an annular four quadrant detector and then determine the factors which limit the minimum measurable deflection angle, such as S/N ratio, current density, dwell time and detector geometry. Knowing these factors enables the experimenter to optimize the set-up for optimum performance of the microscope and to get a clear figure for the achievable field resolution error margins. PMID- 27376784 TI - Radiographer reporting in the UK: is the current scope of practice limiting plain film reporting capacity? AB - OBJECTIVE: To update knowledge on individual radiographer contribution to plain film reporting workloads; to assess whether there is scope to further increase radiographer reporting capacity within this area. METHODS: Reporting radiographers were invited to complete an online survey. Invitations were posted to every acute National Health Service trust in the UK whilst snowball sampling was employed via a network of colleagues, ex-colleagues and acquaintances. Information was sought regarding the demographics, geographical location and anatomical and referral scope of practice. RESULTS: A total of 259 responses were received. 15.1% and 7.7% of respondents are qualified to report chest and abdomen radiographs, respectively. The mean time spent reporting per week is 14.5 h (range 1-37.5). 23.6% of radiographers report only referrals from emergency departments whilst 50.6% of radiographers have limitations on their practice. CONCLUSION: The scope of practice of reporting radiographers has increased since previous studies; however, radiographer reporting of chest and abdomen radiographs has failed to progress in line with demand. There remain opportunities to increase radiographer capacity to assist the management of reporting backlogs. ADVANCES IN KNOWLEDGE: This study is the first to examine demographic factors of reporting radiographers across the UK and is one of the largest in-depth studies of UK reporting radiographers, at individual level, to date. PMID- 27376785 TI - Asymmetric Ring Opening/Cyclization/Retro-Mannich Reaction of Cyclopropyl Ketones with Aryl 1,2-Diamines for the Synthesis of Benzimidazole Derivatives. AB - A highly efficient asymmetric ring-opening/cyclization/retro-Mannich reaction of cyclopropyl ketones with aryl 1,2-diamines has been realized using a chiral N,N' dioxide/Sc(III) catalyst. Benzimidazoles containing chiral side chains were generated under mild reaction conditions in excellent outcomes (up to 99 % yield and 97 % ee). This method also provides efficient access to chiral benzimidazole substituted amide and cycloheptene derivatives. PMID- 27376786 TI - Formation of Reactant Complex Structure for Initiation Reaction of Lactone Ring Opening Polymerization by Cooperation of Multiple Cyclodextrin. AB - Ring-opening polymerization of lactones initiated by cyclodextrins has been reported as a promising polymer synthetic method. To investigate the unknown molecular level mechanism of the initiation reaction, we executed molecular dynamics simulations of model systems composed of single or multiple beta cyclodextrin (beta-CD) molecules in delta-valerolactone (VL) solvent and explored the reactant complex structures satisfying three conditions (VL inclusion in the beta-CD cavity, hydrogen bonding, and nucleophilic attack) at the same time. As a result, we confirmed the formation of the reactant complex structure. Comparison between the single and multiple beta-CD models revealed that the formation is more frequent and the distance for the nucleophilic attack is shorter in the multiple model. Therefore, we anticipate that the reaction proceeds more efficiently by the cooperation of multiple beta-CDs. This finding will contribute to understanding the reaction mechanism from the atomistic point of view. PMID- 27376787 TI - A solid state NMR study of layered double hydroxides intercalated with para-amino salicylate, a tuberculosis drug. AB - Para-amino salicylate (PAS), a tuberculosis drug, was intercalated in three different layered double hydroxides (MgAl, ZnAl, and CaAl-LDH) and the samples were studied by multi-nuclear ((1)H, (13)C, and (27)Al) solid state NMR (SSNMR) spectroscopy in combination with powder X-ray diffraction (PXRD), elemental analysis and IR-spectroscopy to gain insight into the bulk and atomic level structure of these LDHs especially with a view to the purity of the LDH-PAS materials and the concentration of impurities. The intercalations of PAS in MgAl , ZnAl-, and CaAl-LDH's were confirmed by (13)C SSNMR and PXRD. Moreover, (13)C MAS NMR and infrared spectroscopy show that PAS did not decompose during synthesis. Large amounts (20-41%) of amorphous aluminum impurities were detected in the structure using (27)Al single pulse and 3QMAS NMR spectra, which in combination with (1)H single and double quantum experiments also showed that the M(II):Al ratio was higher than predicted from the bulk metal composition of MgAl PAS and ZnAl-PAS. Moreover, the first high-resolution (1)H SSNMR spectra of a CaAl LDH is reported and assigned using (1)H single and double quantum experiments in combination with (27)Al{(1)H} HETCOR. PMID- 27376788 TI - Charged, dipolar soft matter systems from a combined microscopic-mesoscopic viewpoint. AB - As an example of charged, dipolar soft matter, the ionic liquid 1-ethyl-3-methyl imidazolium dicyanamide is studied by coarse-grained molecular dynamics simulations. We focus on the link between microscopic and mesoscopic properties for both structure and dynamics. Thereby, the generalized Kirkwood g K-factor plays a central role in establishing this link which is not possible on the basis of molecular hydrodynamics. The decoupling between translational and rotational motion is indicative of the dynamical heterogeneity in ionic liquids. PMID- 27376789 TI - Towards autonomous motion control in minimally invasive robotic surgery. AB - INTRODUCTION: While autonomous surgical robotic systems exist primarily at the research level, recently these systems have made a strong push into clinical settings. The autonomous or semi-autonomous control of surgical robotic platforms may offer significant improvements to a diverse field of surgical procedures, allowing for high precision, intelligent manipulation of these systems and opening the door to advanced minimally invasive surgical procedures not currently possible. AREAS COVERED: This review highlights those experimental systems currently under development with a focus on in vivo modeling and control strategies designed specifically for the complex and dynamic surgical environment. Expert review: Novel methods for state estimation, system modeling and disturbance rejection, as applied to these devices, continues to improve the performance of these important surgical tools. Procedures such as Natural Orifice Transluminal Endoscopic Surgery and Laparo-Endoscopic Single Site surgery, as well as more conventional procedures such as Colonoscopy, serve to benefit tremendously from the development of these automated robotic systems, enabling surgeons to minimize tissue damage and shorten procedure times while avoiding the consequences of laparotomy. PMID- 27376790 TI - Birch pollen immunotherapy inhibits anaphylaxis to the cross-reactive apple allergen Mal d 1 in mice. AB - BACKGROUND: Cross-reactive apple allergy is a common co-morbidity of birch pollen allergy, caused by the presence of a Bet v 1 homologue allergen in apple, Mal d 1. Treatment of tree pollen hay fever by immunotherapy is well established, but its effect on the accompanying apple allergy is debated. OBJECTIVE: To establish a mouse model of birch pollen induced cross-reactivity to Mal d 1 and investigate the effect of birch pollen immunotherapy on the cross-reactivity to Mal d 1. METHODS: Respiratory allergy was induced in Balb/c mice by intraperitoneal exposure to alum-adsorbed birch pollen extract (BPE) in combination with short or prolonged intranasal exposure to BPE. To evaluate the response to Mal d 1, mice were exposed intraperitoneally to Mal d 1. Immunoglobulin responses and cytokine production by splenocytes were measured by ELISA. Allergic symptoms were evaluated by measuring airway hyper-reactivity and hypothermia as a surrogate marker for anaphylaxis. Immunotherapy was performed subcutaneously with alum adsorbed BPE. RESULTS: Mice exposed to BPE develop cross-reactive IgE to Mal d 1. Early after exposure to BPE, this response is still weak and does not yet translate into anaphylaxis. Interestingly, later re-challenge with BPE increased cross-reactivity to a level where Mal d 1 exposure induced anaphylaxis. Cross sensitization can also be induced by systemic Mal d 1 exposure. Birch pollen immunotherapy significantly reduced the anaphylactic response of mice to Mal d 1. CONCLUSION & CLINICAL RELEVANCE: A mouse model mimicking birch pollen induced cross-reactivity to Mal d 1 was successfully established. In this model, birch pollen immunotherapy significantly ameliorated the anaphylaxis induced by Mal d 1. Our experimental data suggest that boosting of Mal d 1 recognizing immunoglobulins by BP SCIT is important for the amelioration of apple allergy in human. PMID- 27376791 TI - Psychiatry meets pharmacogenetics for the treatment of revolving door patients with psychiatric disorders. AB - INTRODUCTION: Therapeutic failures (TFs) and adverse drug reactions (ADRs), together with the recurring nature of the clinical course of psychiatric disorders, mainly bipolar disorders (BDs), strongly contributed to the prevalence and frequency of hospital readmissions observed in these patients. This is the revolving door (RD) condition, dramatically rising costs for the management of these patients in psychiatric settings. Areas covered: We searched in the medical literature until May 2016 to review the role of functional variants in the cytochrome P450 (CYP) 2D6 gene on observed ADRs and TFs in RD patients with BDs, conferring a different capacity to metabolize psychotropic drugs. Expert commentary: CYP2D6 functional polymorphisms might directly contributed to the prevalence and frequency of the RD condition, commonly observed in BD patients. Although several environmental and socio-demographic/diagnostic variables such as alcohol/drug abuse, and medication non-compliance accounted for a significant proportion of the ability to predict RD prevalence and frequency, the pharmacogenetics of CYP, particularly CYP2D6, may help to identify BD patients at risk for ADRs and TFs. These patients may be addressed towards alternative treatments, thus improving their quality of life, and reducing RD prevalence and frequency and the overall costs for their management. PMID- 27376792 TI - Molybdenum Disulfide-Coated Lithium Vanadium Fluorophosphate Anode: Experiments and First-Principles Calculations. AB - To develop a new anode material to meet the increasing demands of lithium-ion battery, MoS2 is used for the first time to modify the C/LiVPO4 F anode to improve its lithium-storage performance between 3 and 0.01 V. Morphological observations reveal that the MoS2 -modified C/LiVPO4 F particles (M-LVPF) are wrapped by an amorphous carbon as interlayer and layered MoS2 as external surface. Charge-discharge tests show that M-LVPF delivers a high reversible capacity of 308 mAh g(-1) at 50 mA g(-1) . After 300 cycles at 1.0 A g(-1) , a capacity retention of 98.7 % is observed. Moreover, it exhibits high rate capability with a specific capacity of 199 mAh g(-1) at 1.6 A g(-1) . Electrochemical impedance spectroscopy tests indicate that the lithium-ion diffusion and charge-exchange reaction at the surface of M-LVPF are greatly enhanced. First-principles calculations for the MoS2 (001)/C/LiVPO4 F (010) system demonstrate that the absorption of MoS2 on C/LiVPO4 F is exothermic and spontaneous and that the electron transfer at the MoS2 -absorbed C/LiVPO4 F surface is enhanced. PMID- 27376793 TI - A novel NADPH-dependent reductase of Sulfobacillus acidophilus TPY phenol hydroxylase: expression, characterization, and functional analysis. AB - The reductase component (MhpP) of the Sulfobacillus acidophilus TPY multicomponent phenol hydroxylase exhibits only 40 % similarity to Pseudomonas sp. strain CF600 phenol hydroxylase reductase. Amino acid sequence alignment analysis revealed that four cysteine residues (Cys-X 4 -Cys-X 2 -Cys-X 29-35 Cys) are conserved in the N terminus of MhpP for [2Fe-2S] cluster binding, and two other motifs (RXYS and GXXS/T) are conserved in the C terminus for binding the isoalloxazine and phosphate groups of flavin adenine dinucleotide (FAD). Two motifs (S/T-R and yXCGp) responsible for binding to reduce nicotinamide adenine dinucleotide phosphate (NADPH) are also conserved in MhpP, although some residues differ. To confirm the function of this reductase, MhpP was heterologously expressed in Escherichia coli BL21(DE3) and purified. UV-visible spectroscopy and electron paramagnetic resonance spectroscopy revealed that MhpP contains a [2Fe 2S] cluster. MhpP mutants in which the four cysteine residues were substituted via site-directed mutagenesis lost the ability to bind the [2Fe-2S] cluster, resulting in a decrease in enzyme-specific oxidation of NADPH. Thin-layer chromatography revealed that MhpP contains FAD. Substrate specificity analyses confirmed that MhpP uses NADPH rather than NADH as an electron donor. MhpP oxidizes NADPH using cytochrome c, potassium ferricyanide, or nitro blue tetrazolium as an electron acceptor, with a specific activity of 1.7 +/- 0.36, 0.78 +/- 0.13, and 0.16 +/- 0.06 U/mg, respectively. Thus, S. acidophilus TPY MhpP is a novel NADPH-dependent reductase component of phenol hydroxylase that utilizes FAD and a [2Fe-2S] cluster as cofactors. PMID- 27376794 TI - Influence of osmotic stress on the profile and gene expression of surface layer proteins in Lactobacillus acidophilus ATCC 4356. AB - In this work, we studied the role of surface layer (S-layer) proteins in the adaptation of Lactobacillus acidophilus ATCC 4356 to the osmotic stress generated by high salt. The amounts of the predominant and the auxiliary S-layer proteins SlpA and SlpX were strongly influenced by the growth phase and high-salt conditions (0.6 M NaCl). Changes in gene expression were also observed as the mRNAs of the slpA and slpX genes increased related to the growth phase and presence of high salt. A growth stage-dependent modification on the S-layer protein profile in response to NaCl was observed: while in control conditions, the auxiliary SlpX protein represented less than 10 % of the total S-layer protein, in high-salt conditions, it increased to almost 40 % in the stationary phase. The increase in S-layer protein synthesis in the stress condition could be a consequence of or a way to counteract the fragility of the cell wall, since a decrease in the cell wall thickness and envelope components (peptidoglycan layer and lipoteichoic acid content) was observed in L. acidophilus when compared to a non-S-layer-producing species such as Lactobacillus casei. Also, the stationary phase and growth in high-salt medium resulted in increased release of S-layer proteins to the supernatant medium. Overall, these findings suggest that pre growth in high-salt conditions would result in an advantage for the probiotic nature of L. acidophilus ATCC 4356 as the increased amount and release of the S layer might be appropriate for its antimicrobial capacity. PMID- 27376796 TI - Prognostic value of Sox2 expression in digestive tract cancers: A meta-analysis. AB - The aim of the present study was to accurately evaluate the association of Sox2 expression with the survival of patients with digestive tract cancers. Relevant literatures were identified by comprehensively searching databases including the Pubmed, Embase, CBMdisc, and Wanfang (up to October 2014). A meta-analysis was performed to clarify the association between Sox2 expression and overall survival or clinicopathological parameters of patients with digestive tract cancers (esophageal, gastric, and colorectal cancers). The results showed a significant association between high Sox2 expression and poor overall survival in patients with digestive tract carcinomas (HR=1.55, 95% CI=1.04-2.31), especially for patients with esophageal cancer (HR=2.04, 95%CI=1.30-3.22), colorectal cancer (HR=1.40, 95% CI=1.04-1.89), and digestive tract adenocarcinoma (HR=1.80, 95% CI=1.12-2.89), for Europeans (HR=1.98, 95% CI=1.44-2.71) or patients who did not receive neoadjuvant treatment (HR=1.73, 95% CI=1.10-2.72). Furthermore, Sox2 over expression was highly correlated with vascular invasion (OR=1.86, 95% CI=1.25 2.77) and poor differentiation (OR=1.88, 95% CI=1.14-3.08), especially in esophageal and colorectal cancers. In conclusion, Sox2 expression may serve as a novel prognostic factor for patients with digestive tract cancers. Over expression of Sox2 that is correlated with vascular invasion and poor differentiation suggests poor outcomes of patients with digestive tract cancers. PMID- 27376797 TI - A meta-analysis reveals prognostic role of programmed death ligand-1 in Asian patients with non-small cell lung cancer. AB - Accumulating studies explored the clinicopathologic and prognostic value of programmed death ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC), but the results were controversial. We therefore conducted a meta-analysis to evaluate the predictive role of PD-L1 in NSCLC patients. We systematically collected relevant studies from PubMed, Embase, Web of Science and China National Knowledge Infrastructure. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS), and odd ratios (ORs) with 95% CIs for clinicopathologic factors were calculated. A total of 15 studies involving 3605 patients were included in this meta-analysis. The results showed no prognostic role of PD-L1 in the whole patients (HR=1.60, 95% CI: 0.88-2.89, P=0.123). Subgroup analysis showed that PD-L1 was associated with decreased OS in Asian patients (HR=2.00, 95% CI: 1.55-2.57, P<0.001). Among all the clinicopathologic factors, PD-L1 overexpression was significantly in relevance with poor tumor cell differentiation (HR=1.84, 95% CI: 1.49-2.28, P<0.001), late stage (HR=1.21, 95% CI: 1.02-1.43, P=0.026) and anaplastic lymphoma kinase (ALK) translocation (HR=2.63, 95% CI: 1.08-6.40, P=0.034), but not with other factors. In conclusion, our meta-analysis demonstrated that PD-L1 has a prognostic role in Asian patients with NSCLC. PMID- 27376798 TI - Clinicopathological and prognostic significance of hypoxia-inducible factor-1 alpha in lung cancer: a systematic review with meta-analysis. AB - Hypoxia-inducible factor-1 alpha (HIF-1alpha) plays a vital role in the initiation, evaluation and prognosis in lung cancer. The prognostic value of HIF 1alpha reported in diverse study remains disputable. Accordingly, a meta-analysis was implemented to further understand the prognostic role of HIF-1alpha in lung cancer. The relationship between HIF-1alpha and the clinicopathological characteristics and prognosis of lung cancer were investigated by a meta analysis. PubMed and Embase were searched from their inception to January 2015 for observational studies. Fixed-effects or random-effects meta-analyses were used to calculate odds ratios and 95% confidence intervals of different comparisons. A total of 20 studies met the criteria. The results showed that HIF 1alpha expression in lung cancer tissues was significantly higher than that in normal lung tissues. Expression of HIF-1alpha in patients with squamous cell carcinoma was significantly higher than that of patients with adenocarcinomas. Similarly, non-small cell lung cancer (NSCLC) patients had higher HIF-1alpha expression than small cell lung cancer (SCLC) patients. Moreover, lymph node metastasized tissues had higher HIF-1alpha expression than non-lymph node metastasized tissues. A high level HIF-1alpha expression was well correlated with the expression of vascular endothelial growth factor and epidermal growth factor receptor in the NSCLC. Notably, NSCLC or SCLC patients with positive HIF-1alpha expression in tumor tissues had lower overall survival rate than patients with negative HIF-1alpha expression. It was suggested that HIF-1alpha expression may be a prognostic biomarker and a potential therapeutic target for lung cancer. PMID- 27376795 TI - High risk factors of pancreatic carcinoma. AB - Over the past decades, cancer has become one of the toughest challenges for health professionals. The epidemiologists are increasingly directing their research efforts on various malignant tumor worldwide. Of note, incidence of cancers is on the rise more quickly in developed countries. Indeed, great endeavors have to be made in the control of the life-threatening disease. As we know it, pancreatic cancer (PC) is a malignant disease with the worst prognosis. While little is known about the etiology of the PC and measures to prevent the condition, so far, a number of risk factors have been identified. Genetic factors, pre-malignant lesions, predisposing diseases and exogenous factors have been found to be linked to PC. Genetic susceptibility was observed in 10% of PC cases, including inherited PC syndromes and familial PC. However, in the remaining 90%, their PC might be caused by genetic factors in combination with environmental factors. Nonetheless, the exact mechanism of the two kinds of factors, endogenous and exogenous, working together to cause PC remains poorly understood. The fact that most pancreatic neoplasms are diagnosed at an incurable stage of the disease highlights the need to identify risk factors and to understand their contribution to carcinogenesis. This article reviews the high risk factors contributing to the development of PC, to provide information for clinicians and epidemiologists. PMID- 27376799 TI - Thymosin beta4 impeded murine stem cell proliferation with an intact cardiovascular differentiation. AB - Thymosin beta4 (Tbeta4) is a key factor in cardiac development, growth, disease, epicardial integrity, blood vessel formation and has cardio-protective properties. However, its role in murine embryonic stem cells (mESCs) proliferation and cardiovascular differentiation remains unclear. Thus we aimed to elucidate the influence of Tbeta4 on mESCs. Target genes during mESCs proliferation and differentiation were detected by real-time PCR or Western blotting, and patch clamp was applied to characterize the mESCs-derived cardiomyocytes. It was found that Tbeta4 decreased mESCs proliferation in a partial dose-dependent manner and the expression of cell cycle regulatory genes c myc, c-fos and c-jun. However, mESCs self-renewal markers Oct4 and Nanog were elevated, indicating the maintenance of self-renewal ability in these mESCs. Phosphorylation of STAT3 and Akt was inhibited by Tbeta4 while the expression of RAS and phosphorylation of ERK were enhanced. No significant difference was found in BMP2/BMP4 or their downstream protein smad. Wnt3 and Wnt11 were remarkably decreased by Tbeta4 with upregulation of Tcf3 and constant beta-catenin. Under mESCs differentiation, Tbeta4 treatment did not change the expression of cardiovascular cell markers alpha-MHC, PECAM, and alpha-SMA. Neither the electrophysiological properties of mESCs-derived cardiomyocytes nor the hormonal regulation by Iso/Cch was affected by Tbeta4. In conclusion, Tbeta4 suppressed mESCs proliferation by affecting the activity of STAT3, Akt, ERK and Wnt pathways. However, Tbeta4 did not influence the in vitro cardiovascular differentiation. PMID- 27376800 TI - Molecular cloning, characterization and expression analysis of woodchuck retinoic acid-inducible gene I. AB - Cytosolic retinoic acid-inducible gene I (RIG-I) is an important innate immune RNA sensor and can induce antiviral cytokines, e.g., interferon-beta (IFN-beta). Innate immune response to hepatitis B virus (HBV) plays a pivotal role in viral clearance and persistence. However, knowledge of the role that RIG-I plays in HBV infection is limited. The woodchuck is a valuable model for studying HBV infection. To characterize the molecular basis of woodchuck RIG-I (wRIG-I), we analyzed the complete coding sequences (CDSs) of wRIG-I, containing 2778 base pairs that encode 925 amino acids. The deduced wRIG-I protein was 106.847 kD with a theoretical isoelectric point (pI) of 6.07, and contained three important functional structures [caspase activation and recruitment domains (CARDs), DExD/H box helicases, and a repressor domain (RD)]. In woodchuck fibroblastoma cell line (WH12/6), wRIG-I-targeted small interfering RNA (siRNA) down-regulated RIG-I and its downstrean effector-IFN-beta transcripts under RIG-I' ligand, 5'-ppp double stranded RNA (dsRNA) stimulation. We also measured mRNA levels of wRIG-I in different tissues from healthy woodchucks and in the livers from woodchuck hepatitis virus (WHV)-infected woodchucks. The basal expression levels of wRIG-I were abundant in the kidney and liver. Importantly, wRIG-I was significantly up regulated in acutely infected woodchuck livers, suggesting that RIG-I might be involved in WHV infection. These results may characterize RIG-I in the woodchuck model, providing a strong basis for further study on RIG-I-mediated innate immunity in HBV infection. PMID- 27376801 TI - Opacity proteins of neisseria gonorrhoeae in lipooligosaccharide mutants lost ability to interact with neutrophil-restricted CEACAM3 (CD66d). AB - Lipooligosacharide (LOS) of Neisseria gonorrhoeae (gonococci, GC) is involved in the interaction of GC with host cells. Deletion of the alpha-oligosaccharide (alpha-OS) moiety of LOS (lgtF mutant) significantly impairs invasion of GC into epithelial cell lines. GC opacity (Opa) proteins, such as OpaI, mediate phagocytosis and stimulate chemiluminescence responses in neutrophils in part through interaction with members of the carcinoembryonic antigen (CEA) family, which includes CEACAM3 (CD66d), a human neutrophil specific receptor for phagocytosis of bacteria. In the present work, we examined the effects of OpaI expressing lgtF mutant on phagocytosis by HeLa-CEACAM3 cells and chemiluminescence responses in neutrophils. The results showed that lgtF mutant even expressing OpaI completely lost the ability to promote either phagocytosis mediated by CEACAM3 interaction in HeLa cells or chemiluminescence responses in neutrophils. These data indicated that Opa proteins in the lgtF mutant, which might result from the conformational change, cannot be functional. PMID- 27376802 TI - Inhibitory effects of SRT1720 on the apoptosis of rabbit chondrocytes by activating SIRT1 via p53/bax and NF-kappaB/PGC-1alpha pathways. AB - SRT1720, a new discovered drug, was reported to activate silent information regulator 1 (SIRT1) and inhibit the chondrocyte apoptosis. However, the underlying mechanism remains elusive. In the present study, the chondrocytes were extracted from the cartilage tissues of New Zealand white rabbits, cultured in the presence of sodium nitroprusside (SNP) (2.5 mmol/L) and divided into five groups: 1, 5, 10, and 20 MUmol/L SRT1720 groups and blank control group (0 MUmol/L SRT1720). MTT assay was used to detect the chondrocyte viability and proliferation, and DAPI staining and flow cytometry to measure the chondrocyte apoptosis. The expression levels of SIRT1, p53, NF-kappaB/p65, Bax, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha) were detected by Western blotting and the expression levels of SIRT1, type II collagen, and aggrecan mRNA by RT-PCR. The results showed that in the SRT1720 treated groups, the nuclei of chondrocytes were morphologically intact and had uniform chromatin. In the blank control group, nuclear rupture into debris was observed in chondrocytes. With the SRT1720 concentration increasing, the chondrocyte viability increased, the apoptosis rate decreased, the protein expression levels of SIRT1 and PGC-1alpha and the mRNA expression levels of type II collagen and aggrecan increased ({ptP}<0.05), and the expression levels of p53, NF-kappaB and bax decreased (P<0.05). It was suggested that SRT1720 inhibits chondrocyte apoptosis by activating the expression of SIRT1 via p53/bax and NF kappaB/PGC-1alpha pathways. PMID- 27376803 TI - Protective effect of reduced glutathione C60 derivative against hydrogen peroxide induced apoptosis in HEK 293T cells. AB - Hydrogen peroxide (H2O2) and free radicals cause oxidative stress, which induces cellular injuries, metabolic dysfunction, and even cell death in various clinical abnormalities. Fullerene (C60) is critical for scavenging oxygen free radicals originated from cell metabolism, and reduced glutathione (GSH) is another important endogenous antioxidant. In this study, a novel water-soluble reduced glutathione fullerene derivative (C60-GSH) was successfully synthesized, and its beneficial roles in protecting against H2O2-induced oxidative stress and apoptosis in cultured HEK 293T cells were investigated. Fourier Transform infrared spectroscopy and (1)H nuclear magnetic resonance were used to confirm the chemical structure of C60-GSH. Our results demonstrated that C60-GSH prevented the reactive oxygen species (ROS)-mediated cell damage. Additionally, C60-GSH pretreatment significantly attenuated H2O2-induced superoxide dismutase (SOD) consumption and malondialdehyde (MDA) elevation. Furthermore, C60-GSH inhibited intracellular calcium mobilization, and subsequent cell apoptosis via bcl-2/bax-caspase-3 signaling pathway induced by H2O2 stimulation in HEK 293T cells. Importantly, these protective effects of C60-GSH were superior to those of GSH. In conclusion, these results suggested that C60-GSH has potential to protect against H2O2-induced cell apoptosis by scavenging free radicals and maintaining intracellular calcium homeostasis without evident toxicity. PMID- 27376804 TI - High-density lipoprotein cholesterol and in-hospital mortality in patients with acute aortic dissection. AB - The association between high-density lipoprotein cholesterol (HDL-C) and mortality in patients with acute aortic dissection (AAD) is unclear. From January 2007 to January 2014, a total of 928 consecutive AAD patients who were admitted within 48 h after the onset of symptoms were enrolled in the study. Patients were divided into two groups according to whether serum HDL-C level was below the normal lower limit or not. The Cox proportional hazard regression model was used to identify the predictive value of HDL-C for in-hospital mortality in patients with AAD. As compared with normal HDL-C group (n=585), low HDL-C group (n=343) had lower levels of systolic blood pressure and hemoglobin and higher levels of leukocyte, alanine aminotransferase, blood glucose, blood urea nitrogen, creatinine and urea acid. Low HDL-C group had significantly higher in-hospital mortality than normal HDL-C group (21.6% vs. 12.6%, log-rank=10.869, P=0.001). After adjustment for baseline variables including demographics and biologic data, the increased risk of in-hospital mortality in low HDL-C group was substantially attenuated and showed no significant difference (adjusted hazard ratio, 1.23; 95% confidence interval, 0.86-1.77; P=0.259). Low HDL-C is strongly but not independently associated with in-hospital mortality in patients with AAD. PMID- 27376805 TI - Human brucellosis mimicking axial spondyloarthritis: a challenge for rheumatologists when applying the 2009 ASAS criteria. AB - Although the development of the 2009 SpA classification criteria by Assessment of SpondyloArthritis international Society (ASAS) represents an important step towards a better definition of the early disease stage particularly in axial spondyloarthritis (axSpA), the specificity of the criteria has been criticized these days. As the commonest zoonotic infection worldwide, human brucellosis can mimic a large number of diseases, including SpA. This study was performed to determine the frequency of rheumatologic manifestations in patients with brucellosis and the chance of misdiagnosing them as having axSpA in central China. The results showed that clinical manifestations of axSpA could be observed in brucellosis. Over half of patients had back pain, and one fifth of the patients with back pain were less than 45 years old at onset and had the symptom for more than 3 months. Two young males were falsely classified as suffering from axSpA according to the ASAS criteria, and one with MRI proved sacroiliitis was once given Etanercept for treatment. Therefore, differential diagnosis including human brucellosis should always be kept in mind when applying the ASAS criteria, even in traditionally non-endemic areas. PMID- 27376806 TI - Pentoxifylline inhibits liver fibrosis via hedgehog signaling pathway. AB - Infection of schistosomiasis japonica may eventually lead to liver fibrosis, and no effective antifibrotic therapies are available but liver transplantation. Hedgehog (HH) signaling pathway has been involved in the process and is a promising target for treating liver fibrosis. This study aimed to explore the effects of pentoxifylline (PTX) on liver fibrosis induced by schistosoma japonicum infection by inhibiting the HH signaling pathway. Phorbol12-myristate13 acetate (PMA) was used to induce human acute mononuclear leukemia cells THP-1 to differentiate into macrophages. The THP-1-derived macrophages were stimulated by soluble egg antigen (SEA), and the culture supernatants were collected for detection of activation of macrophages. Cell Counting Kit-8 (CCK-8) was used to detect the cytotoxicity of the culture supernatant and PTX on the LX-2 cells. The LX-2 cells were administered with activated culture supernatant from macrophages and(or) PTX to detect the transforming growth factor-beta gene expression. The mRNA expression of shh and gli-1, key parts in HH signaling pathway, was detected. The mRNA expression of shh and gli-1 was increased in LX-2 cells treated with activated macrophages-derived culture supernatant, suggesting HH signaling pathway may play a key role in the activation process of hepatic stellate cells (HSCs). The expression of these genes decreased in LX-2 cells co cultured with both activated macrophages-derived culture supernatant and PTX, indicating PTX could suppress the activation process of HSCs. In conclusion, these data provide evidence that PTX prevents liver fibrogenesis in vitro by the suppression of HH signaling pathway. PMID- 27376808 TI - Protein kinase C enhances the swelling-induced chloride current in human atrial myocytes. AB - Swelling-activated chloride currents (ICl.swell) are thought to play a role in several physiologic and pathophysiologic processes and thus represent a target for therapeutic approaches. However, the mechanism of ICl.swell regulation remains unclear. In this study, we used the whole-cell patch-clamp technique to examine the role of protein kinase C (PKC) in the regulation of ICl.swell in human atrial myocytes. Atrial myocytes were isolated from the right atrial appendages of patients undergoing coronary artery bypass and enzymatically dissociated. ICl.swell was evoked in hypotonic solution and recorded using the whole-cell patch-clamp technique. The PKC agonist phorbol dibutyrate (PDBu) enhanced ICl.swell in a concentration-dependent manner, which was reversed in isotonic solution and by a chloride current inhibitor, 9 anthracenecarboxylicacid. Furthermore, the PKC inhibitor bis-indolylmaleimide attenuated the effect and 4alpha-PDBu, an inactive PDBu analog, had no effect on ICl.swell. These results, obtained using the whole-cell patch-clamp technique, demonstrate the ability of PKC to activate ICl,swell in human atrial myocytes. This observation was consistent with a previous study using a single-channel patch-clamp technique, but differed from some findings in other species. PMID- 27376807 TI - IFN-gamma secretion in gut of Ob/Ob mice after vertical sleeve gastrectomy and its function in weight loss mechanism. AB - Vertical sleeve gastrectomy (VSG) is becoming more and more popular among the world. Despite its dramatic efficacy, however, the mechanism of VSG remains largely undetermined. This study aimed to test interferon (IFN)-gamma secretion n of mesenteric lymph nodes in obese mice (ob/ob mice), a model of VSG, and its relationship with farnesoid X receptor (FXR) expression in the liver and small intestine, and to investigate the weight loss mechanism of VSG. The wild type (WT) mice and ob/ob mice were divided into four groups: A (WT+Sham), B (WT+VSG), C (ob/ob+Sham), and D (ob/ob+VSG). Body weight values were monitored. The IFN gamma expression in mesenteric lymph nodes of ob/ob mice pre- and post-operation was detected by flow cytometry (FCM). The FXR expression in the liver and small intestine was detected by Western blotting. The mouse AML-12 liver cells were stimulated with IFN-gamma at different concentrations in vitro. The changes of FXR expression were also examined. The results showed that the body weight of ob/ob mice was significantly declined from (40.6+/-2.7) g to (27.5+/-3.8) g on the 30th day after VSG (P<0.05). At the same time, VSG induced a higher level secretion of IFN-gamma in mesenteric lymph nodes of ob/ob mice than that pre operation (P<0.05). The FXR expression levels in the liver and small intestine after VSG were respectively 0.97+/-0.07 and 0.84+/-0.07 fold of GAPDH, which were significantly higher than pre-operative levels of 0.50+/-0.06 and 0.48+/-0.06 respectively (P<0.05). After the stimulation of AML-12 liver cells in vitro by different concentrations of IFN-gamma (0, 10, 25, 50, 100, and 200 ng/mL), the relative FXR expression levels were 0.22+/-0.04, 0.31+/-0.04, 0.39+/-0.05, 0.38+/ 0.05, 0.56+/-0.06, and 0.35+/-0.05, respectively, suggesting IFN-gamma could distinctly promote the FXR expression in a dose-dependent manner in comparison to those cells without IFN-gamma stimulation (P<0.05). It was concluded that VSG induces a weight loss in ob/ob mice by increasing IFN-gamma secretion of mesenteric lymph nodes, which then increases the FXR expression of the liver and small intestine. PMID- 27376809 TI - A comparative study of high-viscosity cement percutaneous vertebroplasty vs. low viscosity cement percutaneous kyphoplasty for treatment of osteoporotic vertebral compression fractures. AB - The clinical effects of two different methods-high-viscosity cement percutaneous vertebroplasty (PVP) and low-viscosity cement percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fractures (OVCFs) were investigated. From June 2010 to August 2013, 98 cases of OVCFs were included in our study. Forty-six patients underwent high-viscosity PVP and 52 patients underwent low-viscosity PKP. The occurrence of cement leakage was observed. Pain relief and functional activity were evaluated using the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI), respectively. Restoration of the vertebral body height and angle of kyphosis were assessed by comparing preoperative and postoperative measurements of the anterior heights, middle heights and the kyphotic angle of the fractured vertebra. Nine out of the 54 vertebra bodies and 11 out of the 60 vertebra bodies were observed to have cement leakage in the high viscosity PVP and low-viscosity PKP groups, respectively. The rate of cement leakage, correction of anterior vertebral height and kyphotic angles showed no significant differences between the two groups (P>0.05). Low-viscosity PKP had significant advantage in terms of the restoration of middle vertebral height as compared with the high-viscosity PVP (P<0.05). Both groups showed significant improvements in pain relief and functional capacity status after surgery (P<0.05). It was concluded that high-viscosity PVP and low-viscosity PKP have similar clinical effects in terms of the rate of cement leakage, restoration of the anterior vertebral body height, changes of kyphotic angles, functional activity, and pain relief. Low-viscosity PKP is better than high-viscosity PVP in restoring the height of the middle vertebra. PMID- 27376810 TI - Role of axl in preeclamptic EPCs functions. AB - Axl encodes the tyrosine-protein kinase receptor, participating in the proliferation and migration of many cells. This study examined the role of Axl in functions of endothelial progenitor cells (EPCs). Axl was detected by RT-PCR and Western blotting in both placentas and EPCs from normal pregnancy and preeclampsia patients. The Axl inhibitor, BMS777-607, was used to inhibit the Axl signalling pathway in EPCs. Cell proliferation, differentiation, migration and adhesion were measured by CCK-8 assay, cell differentiation assay, Transwell assay, and cell adhesion assay, respectively. Results showed the expression levels of Axl mRNA and protein were significantly higher in both placentas and EPCs from preeclampsia patients than from normal pregnancy (P<0.05). After treatment with BMS777-607, proliferation, differentiation, migration and adhesion capability of EPCs were all significantly decreased. Our study suggests Axl may play a role in the function of EPCs, thereby involving in the pathogenesis of preeclampsia. PMID- 27376811 TI - Association between p53 polymorphism at codon 72 and recurrent spontaneous abortion. AB - p53 gene plays an important role in apoptosis, which is necessary for successful invasion of trophoblast cells. The change from an arginine (Arg) to a proline (Pro) at codon 72 can influence the biological activity of p53, which predisposes to an increased risk of recurrent spontaneous abortion (RSA). In order to investigate the association between p53 polymorphism at codon 72 and RSA, we conducted this meta-analysis. Pubmed, Embase and Web of science were used to identify the eligible studies. Odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of the association. Six studies containing 937 cases of RSA and 830 controls were included, and there was one study deviated from Hardy-Weinberg equilibrium (HWE). There was a significant association between p53 polymorphism at codon 72 and RSA in recessive model (Pro/Pro vs. Pro/Arg+Arg/Arg; OR=1.60, 95% CI: 1.14-2.24) and co-dominant model (Pro/Pro vs. Arg/Arg; OR=1.47, 95% CI: 1.02-2.12) whether the study that was deviated from HWE was eliminated or not. A significant association was observed in allelic model (Pro vs. Arg; OR=1.28, 95% CI: 1.04-1.57) after exclusion of the study that was deviated from HWE. No association was noted in recessive model (Pro/Pro+Pro/Arg vs. Arg/Arg; OR=1.05, 95% CI: 0.86-1.30) and co-dominant model (Pro/Arg vs. Arg/Arg; OR=0.96, 95% CI: 0.77-1.19). Subgroup analysis by ethnicity also indicated a significant association between p53 polymorphism at codon 72 and RSA in Caucasian group. No heterogeneity and publication bias were found. Our meta analysis implied that p53 polymorphism at codon 72 carries high maternal risk of RSA. PMID- 27376812 TI - Downregulation of inwardly rectifying potassium channel 5.1 expression in C57BL/6J cochlear lateral wall. AB - Age-related hearing loss (AHL) is one of the most common sensory disorders among elderly persons. The inwardly rectifying potassium channel 5.1 (Kir5.1) plays a vital role in regulating cochlear K(+) circulation which is necessary for normal hearing. The distribution of Kir5.1 in C57BL/6J mice cochleae, and the relationship between the expression of Kir5.1 and the etiology of AHL were investigated. Forty C57BL/6J mice were randomly divided into four groups at 4, 12, 24 and 52 weeks of age respectively. The location of Kir5.1 was detected by immunofluorescence technique. The mRNA and protein expression of Kir5.1 was evaluated in mice cochleae using real-time polymerase-chain reactions (RT-PCR) and Western blotting respectively. Kir5.1 was detected in the type II and IV fibrocytes of the spiral ligament in the cochlear lateral wall of C57BL/6J mice. The expression levels of Kir5.1 mRNA and protein in the cochleae of aging C57BL/6J mice were down-regulated. It was suggested that the age-related decreased expression of Kir5.1 in the lateral wall of C57BL/6J mice was associated with hearing loss. Our results indicated that Kir5.1 may play an important role in the pathogenesis of AHL. PMID- 27376813 TI - Clinical and laboratory features, and quality of life assessment in wheat dependent exercise-induced anaphylaxis patients from central China. AB - Wheat dependent exercise-induced anaphylaxis (WDEIA) is a rare but potentially severe food allergy caused by the combination of wheat ingestion and physical exercise. The impact of WDEIA on quality of life (QOL) is unclear. This study characterized the clinical and laboratory features and investigated the QOL in WDEIA patients from Central China. Twenty-eight WDEIA patients were analyzed, and QOL was measured by validated Chinese version Food Allergy Quality of Life Questionnaire-Adult Form (FAQLQ-AF) and Food Allergy Independent Measure (FAIM) after obtaining the diagnosis. The results showed that half of the patients were females. The median onset age was 37 years old. The symptoms occurred within 1 h after wheat ingestion (26/28). Symptoms of anaphylaxis included cutaneous (26/28), respiratory (11/28), gastro-intestinal (5/28) and cardiovascular manifestations (27/28). Skin prick tests were positive to salt soluble (89.3%) and salt insoluble wheat allergen extracts (100%). Positive rate to wheat, gluten and omega-5 gliadin specific IgE was 64.3%, 92.9% and 92.9% respectively. Specific IgE to omega-5 gliadin with a cut-off value 0.83 KU/L offered highly efficient diagnostic criterion for WDEIA (sensitivity: 89.3%; and specificity: 88.9%). The mean scores of FAQLQ-AF and FAIM were 4.70 and 4.98 respectively and level of anti-omega-5 gliadin IgE had positive correlations with FAQLQ scores. Thereby, WDEIA is commonly found in mid-age adults. In most cases, multi-organs especially skin and cardiovascular systems are involved. Salt insoluble wheat allergen skin test and serum specific IgE to gluten and omega-5 gliadin help to diagnose WDEIA. QOL in WDEIA patients is severely impaired. PMID- 27376815 TI - Three-dimensional finite element analysis of a newly designed onplant miniplate anchorage system. AB - The purpose of this research was to evaluate the structural stress and deformation of a newly designed onplant miniplate anchorage system compared to a standard anchorage system. A bone block integrated with a novel miniplate and fixation screw system was simulated in a three-dimensional model and subjected to force at different directions. The stress distribution and deformation of the miniplate system and cortical bone were evaluated using the three-dimensional finite element method. The results showed that the stress on the plate system and bone was linearly proportional to the force magnitude and was higher when the force was in a vertical direction (Y-axis). Stress and deformation values of the two screws (screw 1 and 2) were asymmetric when the force was added along Y-axis and was greater in screw 1. The highest deformation value of the screws was 7.5148 MUm, much smaller than the limit value. The load was decreased for each single miniscrew, and the ability of the new anchorage system to bear the load was also enhanced to some degree. It was suggested that the newly designed onplant miniplate anchorage system is effective, easily implanted and minimally invasive. PMID- 27376814 TI - Immunogenicity and prediction of epitopic region of antigen Ag I/II and glucosyltransferase from Streptococcus mutans. AB - The levels of Streptococcus (S.) mutans infections in saliva were evaluated and a comparison for specific antibody levels among children with different levels of S. mutans infection was made. The promising epitopic regions of antigen AgI/II (PAc) and glucosyltransferase (GTF) for potential vaccine targets related to S. mutans adherence were screened. A total of 94 children aged 3-4 years were randomly selected, including 53 caries-negative and 41 caries-positive children. The values of S. mutans and those of salivary total secretory immunoglobulin A (sIgA), anti-PAc and anti-Glucan binding domain (anti-GLU) were compared to determine the correlation among them. It was found the level of s-IgA against specific antigens did not increase with increasing severity of S. mutans infection, and the complete amino acid sequence of PAc and GTFB was analyzed using the DNAStar Protean system for developing specific anti-caries vaccines related to S. mutans adherence. A significantly positive correlation between the amount of S. mutans and children decayed, missing, and filled teeth index was observed. No significant difference was detected in specific sIgA against PAc or GLU between any two groups. No significant correlation was found between such specific sIgA and caries index. A total of 16 peptides from PAc as well as 13 peptides from GTFB were chosen for further investigation. S. mutans colonization contributed to early children caries as an important etiological factor. The level of sIgA against specific antigens did not increase with increasing severity of S. mutans infection in children. The epitopes of PAc and GTF have been screened to develop the peptide-based or protein-based anti-caries vaccines. PMID- 27376816 TI - Propofol target-controlled infusion modeling in rabbits: Pharmacokinetic and pharmacodynamic analysis. AB - This study aimed to establish a new propofol target-controlled infusion (TCI) model in animals so as to study the general anesthetic mechanism at multi-levels in vivo. Twenty Japanese white rabbits were enrolled and propofol (10 mg/kg) was administrated intravenously. Artery blood samples were collected at various time points after injection, and plasma concentrations of propofol were measured. Pharmacokinetic modeling was performed using WinNonlin software. Propofol TCI within the acquired parameters integrated was conducted to achieve different anesthetic depths in rabbits, monitored by narcotrend. The pharmacodynamics was analyzed using a sigmoidal inhibitory maximal effect model for narcotrend index (NI) versus effect-site concentration. The results showed the pharmacokinetics of propofol in Japanese white rabbits was best described by a two-compartment model. The target plasma concentrations of propofol required at light anesthetic depth was 9.77+/-0.23 MUg/mL, while 12.52+/-0.69 MUg/mL at deep anesthetic depth. NI was 76.17+/-4.25 at light anesthetic depth, while 27.41+/-5.77 at deep anesthetic depth. The effect-site elimination rate constant (ke0) was 0.263/min, and the propofol dose required to achieve a 50% decrease in the NI value from baseline was 11.19 MUg/mL (95% CI, 10.25-13.67). Our results established a new propofol TCI animal model and proved the model controlled the anesthetic depth accurately and stably in rabbits. The study provides a powerful method for exploring general anesthetic mechanisms at different anesthetic depths in vivo. PMID- 27376817 TI - Echocardiographic evaluation of cardiac dyssynchrony in patients with congestive heart failure. AB - The present study investigated the application of echocardiography to evaluation of cardiac dyssynchrony in patients with congestive heart failure (CHF). A total of 348 consecutive CHF patients who were admitted for cardiac resynchronization (CRT) and presented with low ejection fraction (EF) and wide QRS duration were enrolled in this study, along with 388 healthy individuals. Dyssynchrony was assessed based on filling time ratio (FT/RR), left ventricular pre-ejection delay (PED), interventricular mechanical delay (IVMD), longitudinal opposing wall delay (LOWD) and radial septal to posterior wall delay (RSPWD). Response to CRT was defined as a >=15% increase in EF. The results showed that FT/RR was decreased while PED, IVMD, LOWD and RSPWD were increased in the CHF group compared with the control group (P<0.01). In the CHF group, FT/RR was negatively correlated with the QRS duration, LV end-diastolic diameter (LVESd), LV end-diastolic volume (LVEDV) and LV end-systolic volume (LVESV) (P<0.01), but positively with the LVEF (P<0.01). Additionally, PED, IVMD, LOWD and RSPWD were positively correlated with the QRS duration, LVESd, LVEDV and LVESV (P<0.01), but negatively with the LVEF (P<0.01). The CHF group was divided into three subgroups according to the varying degrees of LVEF. FT/RR decreased successively from the LVEF-1 group to the LVEF-2 group to the LVEF-3 group, while the PED, IVMD, LOWD and RSPWD successively increased in the same order (P<0.01). The CHF group was divided into three subgroups according to the varying degrees of QRS duration, and FT/RR decreased successively in a sequence from the QRS-1 group to the QRS-2 group to the QRS-3 group, while the PED, IVMD, LOWD and RSPWD successively increased in the same order (P<0.01). Speckle tracking radial dyssynchrony >=130 ms was predictive of an EF response in patients in QRS-1 group (78% sensitivity, 83% specificity), those in QRS-2 group (83% sensitivity, 77% specificity) and in QRS-3 group (89% sensitivity, 79% specificity). In conclusion, echocardiography is a convenient and sensitive method for evaluating cardiac dyssynchrony in patients with CHF. PMID- 27376818 TI - Evaluating arterial stiffness in type 2 diabetes patients using ultrasonic radiofrequency. AB - Differences in arterial stiffness between the two sides of the carotid arteries were investigated using ultrasonic radiofrequency in 88 patients with type 2 diabetes and 70 controls. The compliance coefficient (CC), pulse wave velocity (PWV), intima-media thickness (CIMT) and diameter (CCAD) of the common carotid arteries (CCAs) were measured. The ratio of the left to right CCAs was calculated to provide four indexes: CC ratio, PWV ratio, CIMT ratio and CCAD ratio. In the diabetes group, the PWV on the left side was significantly higher than that on the right side, while the CC on the left side was significantly lower than that on the right side. The bilateral CIMT was thicker and CCAD was wider, the left PWV traveled faster, and the right CC was higher in the diabetes group than in the control group. The PWV ratio between the two groups was significantly different and correlated positively with duration of diabetes and systolic blood pressure (SBP). The differences between the two sides of CCAs in patients with diabetes suggested that disease duration and SBP were important risk factors for arterial stiffness. Identifying the difference could potentially lead to the much earlier diagnosis of arteriosclerosis. PMID- 27376819 TI - Antioxidant activities of crude phlorotannins from Sargassum hemiphyllum. AB - Brown algae are well known as a source of biologically active compounds, especially those having antioxidant activities, such as phlorotannins. In this study we examined the antioxidant activities of crude phlorotannins extracts (CPEs) obtained from Sargassum hemiphyllum (SH) and fractionated according to the molecular weights. When CPEs were administrated at a dose of 30 mg/kg to Kunming mice pre-treated with carbon tetrachloride (CCl4), the levels of oxidative stress indicators in the liver, kidney and brain were significantly reduced in vivo. All the components of various molecular weight fractions of CPEs exhibited greater scavenging capacities in clearing hydroxyl free radical and superoxide anion than the positive controls gallic acid, vitamin C and vitamin E. Particularly, the components greater than 30 kD obtained from ethyl acetate phase showed the highest antioxidant capacities. These results indicated that SH is a potential source for extracting phlorotannins, the algal antioxidant compounds. PMID- 27376820 TI - Anti-inflammatory and analgesic effects of Bi-yuan-ling granules. AB - Bi-yuan-ling granule (BLG) is a traditional Chinese medicine compound composed mainly of baicalin and chlorogenic acid. It has been demonstrated to be clinically effective for various inflammatory diseases such as acute rhinitis, chronic rhinitis, atrophic rhinitis and allergic rhinitis. However, the underlying mechanisms of BLG against these diseases are not fully understood. This study aimed to explore the anti-inflammatory and analgesic activities of BLG, and examine its protective effects on mouse acute lung injury (ALI). The hot plate test and acetic acid-induced writhing assay in Kunming mice were adopted to evaluate the pain-relieving effects of BLG. The anti-inflammatory activities of BLG were determined by examining the effects of BLG on xylene-caused ear swelling in Kunming mice, the cotton pellet-induced granuloma in rats, carrageenan-induced hind paw edema and lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The results showed that BLG at 15.5 mg/g could significantly relieve the pain by 82.5% (P<0.01) at 1 h after thermal stimulation and 91.2% (P<0.01) at 2 h after thermal stimulation. BLG at doses of 7.75 and 15.5 mg/g reduced the writhing count up to 33.3% (P<0.05) and 53.4% (P<0.01), respectively. Additionally, the xylene-induced edema in mice was markedly restrained by BLG at 7.75 mg/g (P<0.05) and 15.5 mg/g (P<0.01). BLG at 5.35 and 10.7 mg/g significantly reduced paw edema by 34.8% (P<0.05) and 37.9% (P<0.05) at 5 h after carrageenan injection. The granulomatous formation of the cotton pellet was profoundly suppressed by BLG at 2.68, 5.35 and 10.7 mg/g by 15.4%, 38.2% (P<0.01) and 58.9% (P<0.001), respectively. BLG also inhibited lung W/D ratio and the release of prostaglandin E2 (PGE2) in ALI mice. In addition, the median lethal dose (LD50), median effective dose (ED50) and half maximal inhibitory concentration (IC50) of BLG were found to be 42.7, 3.2 and 12.33 mg/g, respectively. All the findings suggest that BLG has significantly anti inflammatory and analgesic effects and it may help reduce the damage of ALI. PMID- 27376821 TI - In silico investigation of agonist activity of a structurally diverse set of drugs to hPXR using HM-BSM and HM-PNN. AB - The human pregnane X receptor (hPXR) plays a critical role in the metabolism, transport and clearance of xenobiotics in the liver and intestine. The hPXR can be activated by a structurally diverse of drugs to initiate clinically relevant drug-drug interactions. In this article, in silico investigation was performed on a structurally diverse set of drugs to identify critical structural features greatly related to their agonist activity towards hPXR. Heuristic method (HM) Best Subset Modeling (BSM) and HM-Polynomial Neural Networks (PNN) were utilized to develop the linear and non-linear quantitative structure-activity relationship models. The applicability domain (AD) of the models was assessed by Williams plot. Statistically reliable models with good predictive power and explain were achieved (for HM-BSM, r (2)=0.881, q LOO (2) =0.797, q EXT (2) =0.674; for HM PNN, r (2)=0.882, q LOO (2) =0.856, q EXT (2) =0.655). The developed models indicated that molecular aromatic and electric property, molecular weight and complexity may govern agonist activity of a structurally diverse set of drugs to hPXR. PMID- 27376822 TI - A protocol for developing a clinical practice guideline for therapeutic drug monitoring of vancomycin. AB - This study aimed to develop a guideline for therapeutic drug monitoring (TDM) of vancomycin. We adopted the new guideline definition from the Institute of Medicine (IOM), adhered closely to the six domains of the Appraisal of Guidelines for Research & Evaluation II (AGREE II), and made recommendations based on systematic reviews. We established a Guideline Steering Group and a Guideline Development Group, formulated 12 questions in the form of Population, Intervention, Comparison, Outcome (PICO) and completed a literature search. As far as we know, we will develop the first evidenced-based guideline for vancomycin TDM under the framework of the Grade of Recommendations Assessment, Development and Evaluation (GRADE). PMID- 27376823 TI - Sarcopenia in critically ill patients. AB - Sarcopenia occurring as a primary consequence of aging and secondary due to certain medical problems including chronic disease, malnutrition and inactivity is a progressive generalized loss of skeletal muscle mass, strength and function. The prevalence of sarcopenia increases with aging (approximately 5-13 % in the sixth and seventh decades). However, data showing the prevalence and clinical outcomes of sarcopenia in intensive care units (ICUs) are limited. A similar condition to sarcopenia in the ICU, called ICU-acquired weakness (ICU-AW), has been reported more frequently. Here, we aim to examine the importance of sarcopenia, especially ICU-AW, in ICU patients via related articles in Medline. PMID- 27376824 TI - Predictive risk factors for radiation retinopathy and optic neuropathy after proton beam therapy for uveal melanoma. AB - PURPOSE: This study was performed in order to evaluate the incidence of radiation retinopathy and optic neuropathy occurring after proton beam therapy for uveal melanoma. METHODS: Included in this study were all patients who had been treated with primary proton beam therapy for uveal melanoma at the oncology service between May 1998 and June 2014 with a minimum follow-up of 12 months. Excluded were all patients who underwent re-irradiation, or vitrectomy due to exudative retinal detachment or for tumor-resection. RESULTS: During this period, 1127 patients matched the inclusion criteria, of whom 768 (68.1 %) and 463 (41.0 %) developed radiation retinopathy and optic neuropathy after a median time of 18.9 months (2.0-99.84 months) and 19.8 months (0.2-170.4 months), respectively. Mean follow-up was 53.4 months (12-170.4 months). Included were 558 men (49.5 %) and 569 women (50.5 %). Mean age was 61 years (16-89 years). Visual acuity slightly decreased from initial levels of 0.3 logMAR-0.4 logMAR in patients without developing any radiation-induced complication but severely decreased to 1.0 logMAR or 1.5 logMAR in the case of developing radiation retinopathy only or optic neuropathy, respectively. Independent risk factors for radiation retinopathy were a centrally (<2.5 mm from sensitive structures) located tumor or a thick tumor located more than 2.5 mm from sensitive structures, while those for radiation optic neuropathy comprised a short distance and applied dose to the optic disk. CONCLUSION: The risk for radiation retinopathy is higher in central uveal melanoma. Mid-/peripheral tumors are at high risk for radiation retinopathy and maculopathy if presenting with increased thickness. PMID- 27376825 TI - New azo-decorated N-pyrrolidinylthiazoles: synthesis, properties and an unexpected remote substituent effect transmission. AB - New 5-azo substituted thiazole derivatives have been obtained, under mild conditions and in good yields, by the reaction between 2-N-pyrrolidinylthiazole and a series of aryldiazonium salts bearing, mainly in the para position, groups with different electronic effects. The NMR spectra of the products show broad signals of the methylene groups in the alpha position to the pyrrolidinyl nitrogen, suggesting a hindered rotation around the C2-N bond, of which a double bond character was also evidenced by X-ray diffraction analyses. The free energies of activation for the rotational processes have been obtained from (1)H NMR experiments and computer simulations at different temperatures and provided good correlation with the sigma constants of the substituents on the 'remote' benzene ring. This represents an unexpected and peculiar result since the restricted rotation around the C2-N bond was shown to be influenced by a substituent situated very far away. 2,4-Di-N-pyrrolidinylthiazole showed a much greater reactivity than 2-N-pyrrolidinylthiazole with aryldiazonium salts. PMID- 27376826 TI - A allele of SNP12 in estrogen receptor 1 was a risk factor for cryptorchidism in Asians: a systematic review with meta-analysis and trial sequential analysis. AB - OBJECTIVE: Some studies have been carried out to evaluate the association between SNP12 in estrogen receptor 1 and cryptorchidism, but the results remain inconsistent. We carried out a meta-analysis to explore the association between this polymorphism and cryptorchidism risk. METHODS: All eligible studies were searched in PubMed, Web of Science, Embase and Cochrane Library. Pooled odds ratios, with 95 % confidence intervals, were assessed for the association using fixed- and random-effects models. RESULTS: Overall, four case-control studies (363 cases, 415 controls) were included in the meta-analysis. No significant publication bias (P Begg = 0.308, P Egger = 0.288) was found. A allele of SNP12 in estrogen receptor 1 was protective factor to cryptorchidism in allele model, dominant genetic model and heterozygote comparison in Caucasians, but the result was turned out to be false positive by trial sequential analysis. However, A in allele model was risk factor to cryptorchidism in Asians (odds ratio 2.02, 95 % confidence interval 1.03-3.01, p = 0.946 for heterogeneity) and the result was turned out to be true positive by trial sequential analysis, even though there were merely two original studies. CONCLUSIONS: The results of this meta-analysis suggest that A allele of SNP12 in estrogen receptor 1 may increase the risk of cryptorchidism in Asians. Meanwhile, further well-designed studies with large sample sizes are required to confirm the present findings, especially in Caucasians. PMID- 27376827 TI - Practice variability exists in the management of high-grade pediatric pancreatic trauma. AB - PURPOSE: Management of high-grade pancreatic trauma in children is controversial, although recent evidence supports early operation. We sought to evaluate whether practice variability exists regarding the management of these rare and complex injuries. METHODS: A study group of pediatric trauma centers within the Pediatric Trauma Society completed a survey following a query of their institutional database. Results are presented using descriptive statistics. RESULTS: Over a 3 year period (2012-2014), 123 pancreatic injuries (grades II-IV) were reported from 19 pediatric trauma centers (median 6, range 1-22). Sixty-two injuries involving injury to the pancreatic duct (clear/suspected) were reported (median 1, range 0-9). Of these, 49 % were managed with non-operative management (NOM) and 51 % with operative management. Surgeons at the majority (63 %) of institutions used both approaches. Of the operative cases, 21 % were laparoscopic. There was wide variability in clinical management of NOM patients: the most common feeding strategy was reported by 52 % of centers, percutaneous drainage of traumatic pseudocyst by 42 % and ERCP (early/after pseudocyst) by 72 %. CONCLUSION: Wide practice variability exists among North American pediatric surgeons regarding both the initial approach to high-grade pancreatic injury and non-operative management. These results highlight the need for a prospective trial to determine the optimal strategy for these patients. PMID- 27376828 TI - Mechanism of Inhibition of Hsp90 Dimerization by Gyrase B Inhibitor Coumermycin A1 (C-A1) Revealed by Molecular Dynamics Simulations and Thermodynamic Calculations. AB - Heat shock protein (Hsp) 90 an emerging and attracting target in the anti-HIV drug discovery process due to the key role it plays in the pathogenicity of HIV-1 virus. In this research study, long-range all-atom molecular dynamics simulations were engaged for the bound and the unbound proteins to enhance the understanding of the molecular mechanisms of the Hsp90 dimerization and inhibition. Results evidently showed that coumermycin A1 (C-A1), a recently discovered Hsp90 inhibitor, binds at the dimer's active site of the Hsp90 protein and leads to a substantial parting between dimeric opposed residues, which include Arg591.B, Lys594.A, Ser663.A, Thr653.B, Ala665.A, Thr649.B, Leu646.B and Asn669.A. Significant differences in magnitudes were observed in radius of gyration, root mean-square deviation and root-mean-square fluctuation, which confirms a reasonably more flexible state in the apo conformation associated with it dimerization. In contrast, the bound conformer of Hsp90 showed less flexibility. This visibly highpoints the inhibition process resulting from the binding of the ligand. These findings were further validated by principal component analysis. We believe that the detailed dynamic analyses of Hsp90 presented in this study, would give an imperative insight and better understanding to the function and mechanisms of inhibition. Furthermore, information obtained from the binding mode of the inhibitor would be of great assistance in the design of more potent inhibitors against the HIV target Hsp90. PMID- 27376829 TI - Development and validation of rapid multiresidue and multi-class analysis for antibiotics and anthelmintics in feed by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. AB - A new multi-residue method for the analysis of veterinary drugs, namely amoxicillin, chlortetracycline, colistins A and B, doxycycline, fenbendazole, flubendazole, ivermectin, lincomycin, oxytetracycline, sulfadiazine, tiamulin, tilmicosin and trimethoprim, was developed and validated for feed. After acidic extraction, the samples were centrifuged, purified by SPE and analysed by ultra high-performance liquid chromatography coupled to tandem mass spectrometry. Quantitative validation was done in accordance with the guidelines laid down in European Commission Decision 2002/657/CE. Matrix-matched calibration with internal standards was used to reduce matrix effects. The target level was set at the authorised carryover level (1%) and validation levels were set at 0.5%, 1% and 1.5%. Method performances were evaluated by the following parameters: linearity (0.986 < R(2) < 0.999), precision (repeatability < 12.4% and reproducibility < 14.0%), accuracy (89% < recovery < 107%), sensitivity, decision limit (CCalpha), detection capability (CCbeta), selectivity and expanded measurement uncertainty (k = 2).This method has been used successfully for three years for routine monitoring of antibiotic residues in feeds during which period 20% of samples were found to exceed the 1% authorised carryover limit and were deemed non-compliant. PMID- 27376830 TI - MicroRNA-21 promotes the proliferation and invasion of cholesteatoma keratinocytes. AB - CONCLUSIONS: The present study revealed that miR-21 promotes the proliferation and invasion of cholesteatoma keratinocytes. These results provide a partial explanation for the more aggressive clinical behavior observed in cholesteatoma. OBJECTIVE: This study aims to investigate the post-transcriptional regulatory effects that control proliferation, apoptosis, and invasion in cholesteatoma keratinocytes. In particular, the potential role of miR-21 was focused on in this study. METHODS: Thirty cholesteatoma tissues were processed for RNA and cell culture. Cholesteatoma keratinocytes were transfected with miR-21 mimics, miR-21 inhibitors, or negative control miRNAs; and growth curves were drawn. RT-PCR was used to assess the expression levels of miR-21. EdU incorporation assay and TUNEL staining were used to assess the proliferation and apoptosis of cholesteatoma keratinocytes, respectively. The invasive abilities of cholesteatoma keratinocytes were examined using 6-well Transwell plates. RESULTS: MiRNA-21 was upregulated when cholesteatoma keratinocytes were transfected with miR-21 mimics. Furthermore, the number of proliferative EdU + cells increased in cholesteatoma keratinocytes transfected with miR-21 mimics; and the number of TUNEL-positive cells also increased in cells transfected with miR-21 mimics. In addition, the number of migrated cells transfected with miR-21 mimics was higher, compared with migrated cells transfected miR-21 inhibitors or control miRNA. PMID- 27376831 TI - Cardiovascular safety of empagliflozin in patients with type 2 diabetes: a meta analysis of data from randomized placebo-controlled trials. AB - AIM: To assess the effect of empagliflozin on cardiovascular (CV) risk in patients with type 2 diabetes (T2DM) through a meta-analysis of data from eight placebo-controlled trials. METHODS: Data were analysed from eight randomized placebo-controlled trials undertaken to investigate the efficacy and safety of empagliflozin 10 and 25 mg once daily in patients with T2DM, comprising patients at low/medium and high CV risk. Suspected CV events were prospectively adjudicated. The empagliflozin 10 and 25 mg groups were pooled for the primary analysis. The primary endpoint was a composite of CV death, non-fatal myocardial infarction (MI), non-fatal stroke and hospitalization for unstable angina [4 point major adverse CV events (MACE)]. The secondary endpoint was a composite of CV death, non-fatal MI and non-fatal stroke (3-point MACE). Risk estimates were calculated using Cox regression analysis. RESULTS: A total of 3835 patients received placebo and 7457 received empagliflozin. Total exposure was 7448.3 years for placebo and 15482.1 years for empagliflozin. Four-point MACE occurred in 365 (9.5%) patients receiving placebo and 635 (8.5%) patients receiving empagliflozin [hazard ratio for empagliflozin vs. placebo 0.86 (95% CI 0.76, 0.98)]. Three point MACE occurred in 307 (8.0%) patients receiving placebo and 522 (7.0%) patients receiving empagliflozin [hazard ratio for empagliflozin vs. placebo 0.84 (95% CI 0.73, 0.96)]. CONCLUSIONS: In a meta-analysis of data from eight randomized trials involving 11 292 patients with T2DM at low/medium or high CV risk, empagliflozin was associated with a reduced risk of 4-point MACE and 3 point MACE compared with placebo. PMID- 27376832 TI - Improving green waste composting by addition of sugarcane bagasse and exhausted grape marc. AB - The composting of lignocellulosic waste into compost is a potential way of sustainably disposing of a waste while generating a useful product. The current study determined whether the addition of sugarcane bagasse (SCB) (at 0, 15, and 25%) and/or exhausted grape marc (EGM) (at 0, 10, and 20%) improved the two-stage composting of green waste (GW). The combined addition of SCB and EGM improved composting conditions and the quality of the compost product in terms of temperature, water-holding capacity, particle-size distribution, coarseness index, pH, electrical conductivity, water-extractable organic carbon and nitrogen, microbial numbers, enzymatic activities, polysaccharide and lignin content, nutrient content, respiration, and phytotoxicity. The optimal two-stage composting and the best quality compost were obtained with the combined addition of 15% SCB and 20% EGM. With the optimized two-stage composting method, the compost matured in only 21days rather than in the 90-270days required for traditional composting. PMID- 27376833 TI - Using tobacco waste extract in pre-culture medium to improve xylose utilization for l-lactic acid production from cellulosic waste by Rhizopus oryzae. AB - The aim of this work was to study the high-titer l-lactic acid production from cellulosic waste using Rhizopus oryzae. The tobacco waste water-extract (TWE) added with 5g/L glucose and 0.1g/L vitamin C was optimized as pre-culture medium for R. oryzae. Results found that compared to traditional pre-culture medium, it improved xylose consumption rate up to 2.12-fold and enhanced l-lactic acid yield up to 1.73-fold. The highest l-lactic acid concentration achieved was 173.5g/L, corresponding to volumetric productivity of 1.45g/Lh and yield of 0.860g/g total reducing sugar in fed-batch fermentation. This process achieves efficient production of polymer-grade l-lactic acid from cellulosic feedstocks, lowers the cost of fungal cell pre-culture and provides a novel way for re-utilization of tobacco waste. PMID- 27376834 TI - Investigation of the adsorption-reduction mechanisms of hexavalent chromium by ramie biochars of different pyrolytic temperatures. AB - To investigate the relationship between Cr(VI) adsorption mechanisms and physio chemical properties of biochar, ramie residues were oxygen-limited pyrolyzed under temperature varying from 300 to 600 degrees C. Batch adsorption experiments indicated that higher pyrolysis temperature limits Cr(VI) sorption in terms of capacity and affinity due to a higher aromatic structure and fewer polar functional groups in biochar. Both electrostatic (physical) and ionic (chemical) interactions were involved in the Cr(VI) removal. For low-temperature biochar, the simple physical adsorption was limited and the significant improvement in Cr(VI) sorption was attributed to abundant carboxyl and hydroxyl groups. The adsorption-reduction mechanisms could be concluded that Cr(VI) ions were electrostatically attracted by the positively charged biochar surface and reduced to Cr(III), and then the converted Cr(III) was retained or discharged into the solution. The study demonstrates ramie residues can be converted into biochar as a low-cost and effective sorbent for Cr(VI) removal. PMID- 27376835 TI - Improvement of poly-gamma-glutamic acid biosynthesis in a moving bed biofilm reactor by Bacillus subtilis NX-2. AB - The production of poly-gamma-glutamic acid (gamma-PGA) by Bacillus subtilis NX-2 using a moving bed biofilm reactor (MBBR) system was tested for the first time in this study. Polypropylene TL-2 was chosen as a suitable carrier, and gamma-PGA concentration of 42.7+/-0.86g/L and productivity of 0.59+/-0.06g/(Lh) were obtained in batch fermentation. After application of the strategy of dissolved oxygen (DO)-stat feeding, higher gamma-PGA concentration and productivity were achieved than with glucose feedback feeding. Finally, the repeated fed-batch cultures implemented in the MBBR system showed high stability, and the maximal gamma-PGA concentration and productivity of 74.2g/L and 1.24g/(Lh) were achieved, respectively. In addition, the promotion of oxygen transfer by an MBBR carrier was well explained by a computational fluid dynamics (CFD) simulation. These results suggest that an MBBR system could be applied to large-scale gamma-PGA production. PMID- 27376836 TI - "I'm taking control": how people living with HIV/AIDS manage stigma in health interactions. AB - Despite international efforts, stigma is still a significant issue for people living with HIV/AIDS (PLWHA). This paper explores the stigma encountered in health interactions, focusing on strategies PLWHA use to manage and reduce it. It is hoped that our findings will improve future interactions by contributing towards a more understanding practitioner-patient relationship. The data have been drawn from a small qualitative study conducted in Christchurch, New Zealand. Fourteen participants took part in semi-structured face-to-face interviews in 2013 and 11 of these participants were then interviewed again in 2014. Codes and themes were developed through inductive thematic analysis of the interview transcripts. Our findings identified that whilst the majority of participants had positive experiences, nearly all had faced stigma during their health interactions. Most of these encounters were due to healthcare workers holding exaggerated fears of transmission or not maintaining confidentiality and privacy. The main way that participants managed this stigma was through seeking control in their interactions. This overarching strategy could be further divided into three key themes: selective disclosure of their HIV status, self-advocacy and developing their HIV knowledge. We discuss these findings in the context of the current literature, comparing our results to strategies that have been previously identified in social settings. PMID- 27376837 TI - The reminiscence bump without memories: The distribution of imagined word-cued and important autobiographical memories in a hypothetical 70-year-old. AB - The reminiscence bump is the disproportionate number of autobiographical memories dating from adolescence and early adulthood. It has often been ascribed to a consolidation of the mature self in the period covered by the bump. Here we stripped away factors relating to the characteristics of autobiographical memories per se, most notably factors that aid in their encoding or retention, by asking students to generate imagined word-cued and imagined 'most important' autobiographical memories of a hypothetical, prototypical 70-year-old of their own culture and gender. We compared the distribution of these fictional memories with the distributions of actual word-cued and most important autobiographical memories in a sample of 61-70-year-olds. We found a striking similarity between the temporal distributions of the imagined memories and the actual memories. These results suggest that the reminiscence bump is largely driven by constructive, schematic factors at retrieval, thereby challenging most existing theoretical accounts. PMID- 27376838 TI - Nitric oxide increases the migratory activity of non-small cell lung cancer cells via AKT-mediated integrin alphav and beta1 upregulation. AB - BACKGROUND: Previously, nitric oxide (NO) has been found to affect the metastatic behavior of various types of cancer. In addition, it has been found that alterations in integrin expression may have profound effects on cancer cell survival and migration. Here, we aimed at assessing the effects of non-toxic concentrations of NO on human non-small cell lung cancer (NSCLC) cells, including the expression of integrins and the migration of these cells. METHODS: The cytotoxic and proliferative effects of NO on human NSCLC-derived H460, H292 and H23 cells were tested by MTT assay. The migration capacities of these cells was evaluated by wound healing and transwell migration assays. The expression of integrins and migration-associated proteins was determined by Western blot analyses. RESULTS: We found that NO treatment caused a significant increase in the expression of integrin alphav and beta1 in all three NSCLC-derived cell lines tested. Known migration-associated proteins acting downstream of these integrins, including focal adhesion kinase (FAK), active RhoA (Rho-GTP) and active cell division control 42 (Cdc42-GTP), were found to be significantly activated in response to NO. In addition, we found that NO-treated cells showed an increased motility and that this motility was associated with a significant increase in the number of filopodia per cell. We also found that NO-treated cells exhibited increased active protein kinase G (PKG), protein kinase B (AKT) and FAK expression levels. Using a pharmacological approach, we found that the integrin modulating effect of NO is most likely brought about by a PKG/AKT-dependent mechanism, since the observed changes in integrin expression were abolished by AKT inhibitors, but not by FAK inhibitors. CONCLUSION: Our data suggest a novel role of NO in the regulation of integrin expression and, concomitantly, the migratory capacity of NSCLC cells. PMID- 27376840 TI - Alendronate- and risedronate-induced acute polyarthritis. AB - Bisphosphonates are the mainstay treatment for postmenopausal osteoporosis. Although bisphosphonates are safety drugs, they have numerous side-effects such as arthralgia, elevated erythrocyte sedimentation rate and C-reactive protein, gastrointestinal disturbances, and flu-like illness with symptoms of fatigue, fever, chills, malaise, and myalgia. We present a case of acute polyarthritis after administration of alendronate and risedronate in a 52-year-old woman. To the best of the author's knowledge, this is the first case of acute polyarthritis induced by per os administration of both alendronate and risedronate during weekly usage. This is a report of a 52-year-old woman admitted to our hospital every week in a month, within 48 h, after receiving three times alendronate and one time risedronate with diffuse arthralgias, miyalgias, and swelling with effusions in both wrists, both ankles, interphalangeal joints in both hands and feet, and in both knees. When we discontinued alendronate and risedronate, oral raloxifene (60 mg/day) with oral calcium (1 g/day), and vitamin D3 (800 IU/day) was initiated. The symptoms regressed in 1 week. During the 1 year follow-up period, no myalgia, arthritis, or synovitis was detected. The side-effects of bisphosphonates are rarely reported in the literature. We believe that the prevalance of these side-effects would increase by closer follow-up of patients receiving these medications. To our knowledge, this patient is the first reported case of acute polyarthritis induced by per os administration of both alendronate and risedronate during weekly usage. PMID- 27376839 TI - Hypoxia-inducible microRNA-488 regulates apoptosis by targeting Bim in osteosarcoma. AB - BACKGROUND: Osteosarcoma is a malignant bone cancer of which the survival rate is still low. One reason for this low survival rate is drug resistance. In the past, it has been shown that microRNAs may play critical roles in osteosarcoma development and drug resistance. The mechanisms by which osteosarcoma cells acquire this resistance have, however, remained largely unknown. Here, we aimed at assessing the role of microRNA-488 in the acquisition of drug resistance by osteosarcoma cells. METHODS: Quantitative RT-PCR was used to measure the expression of microRNA-488 in primary osteosarcoma samples and in osteosarcoma derived cells, whereas microRNA-488 mimics and inhibitors were used to modify its expression in these cells. Luciferase reporter, Western blotting, cell viability, apoptosis and ChIP assays were used to assess the various effects of modified microRNA-488 expression in osteosarcoma-derived cells. RESULTS: We found that microRNA-488 is over-expressed in primary osteosarcoma tissues and osteosarcoma derived cells and that hypoxia can induce microRNA-488 expression via binding to the hypoxia response element (HRE) in its promoter. We also found that exogenous over-expression of microRNA-488 promotes the proliferation, reduces the apoptosis and decreases the sensitivity to chemotherapy (doxorubicin) of osteosarcoma cells via direct targeting of the tumor suppressor Bim, which is a mediator of apoptosis. In contrast, we found that transfection of a microRNA-488 inhibitor resulted in an increase in both apoptosis and drug sensitivity, and a decrease in proliferation. CONCLUSIONS: Our data suggest that miRNA-488 may serve as a predictor of response to chemotherapy and as a therapeutic target in human osteosarcomas. PMID- 27376841 TI - Band gap in tubular pillar phononic crystal plate. AB - In this paper, a phononic crystal (PC) plate with tubular pillars is presented and investigated. The band structures and mode displacement profiles are calculated by using finite element method. The result shows that a complete band gap opens when the ratio of the pillar height to the plate thickness is about 1.6. However, for classic cylinder pillar structures, a band gap opens when the ratio is equal or greater than 3. A tubular pillar design with a void room in it enhances acoustic multiple scattering and gives rise to the opening of the band gap. In order to verify it, a PC structure with double tubular pillars different in size (one within the other) is introduced and a more than 2times band gap enlargement is observed. Furthermore, the coupling between the resonant mode and the plate mode around the band gap is characterized, as well as the effect of the geometrical parameters on the band gap. The behavior of such structure could be utilized to design a pillar PC with stronger structural stability and to enlarge band gaps. PMID- 27376843 TI - Long-term clinical evaluation of the automatic stance-phase lock-controlled prosthetic knee joint in young adults with unilateral above-knee amputation. AB - PURPOSE: The purpose of this study was to clinically evaluate the automatic stance-phase lock (ASPL) knee mechanism against participants' existing weight activated braking (WAB) prosthetic knee joint. METHOD: This prospective crossover study involved 10 young adults with an above-knee amputation. Primary measurements consisted of tests of walking speeds and capacity. Heart rate was measured during the six-minute walk test and the Physiological Cost Index (PCI) which was calculated from heart rate estimated energy expenditure. Activity was measured with a pedometer. User function and quality of life were assessed using the Lower Limb Function Questionnaire (LLFQ) and Prosthetic Evaluation Questionnaire (PEQ). Long-term follow-up over 12 months were completed. RESULTS: Walking speeds were the same for WAB and APSL knees. Energy expenditure (PCI) was lower for the ASPL knees (p = 0.007). Step counts were the same for both knees, and questionnaires indicated ASPL knee preference attributed primarily to knee stability and improved walking, while limitations included terminal impact noise. Nine of 10 participants chose to keep using the ASPL knee as part of the long term follow-up. CONCLUSIONS: Potential benefits of the ASPL knee were identified in this study by functional measures, questionnaires and user feedback, but not changes in activity or the PEQ. PMID- 27376844 TI - [On the assessment of noise-induced hearing loss]. PMID- 27376842 TI - The plastoquinol-plastoquinone exchange mechanism in photosystem II: insight from molecular dynamics simulations. AB - In the photosystem II (PSII) of oxygenic photosynthetic organisms, the reaction center (RC) core mediates the light-induced electron transfer leading to water splitting and production of reduced plastoquinone molecules. The reduction of plastoquinone to plastoquinol lowers PSII affinity for the latter and leads to its release. However, little is known about the role of protein dynamics in this process. Here, molecular dynamics simulations of the complete PSII complex embedded in a lipid bilayer have been used to investigate the plastoquinol release mechanism. A distinct dynamic behavior of PSII in the presence of plastoquinol is observed which, coupled to changes in charge distribution and electrostatic interactions, causes disruption of the interactions seen in the PSII-plastoquinone complex and leads to the "squeezing out" of plastoquinol from the binding pocket. Displacement of plastoquinol closes the second water channel, recently described in a 2.9 A resolution PSII structure (Guskov et al. in Nat Struct Mol Biol 16:334-342, 2009), allowing to rule out the proposed "alternating" mechanism of plastoquinol-plastoquinone exchange, while giving support to the "single-channel" one. The performed simulations indicated a pivotal role of D1-Ser264 in modulating the dynamics of the plastoquinone binding pocket and plastoquinol-plastoquinone exchange via its interaction with D1-His252 residue. The effects of the disruption of this hydrogen bond network on the PSII redox reactions were experimentally assessed in the D1 site-directed mutant Ser264Lys. PMID- 27376845 TI - Fatigue Improvement after Switching Multiple Sclerosis Treatment from Interferon beta to Glatiramer Acetate in Clinical Practice. AB - BACKGROUND/AIMS: The immunomodulatory effect of glatiramer acetate may help in reducing multiple sclerosis (MS)-related fatigue; however, evidence to prove this notion especially after switching from another immunomodulatory therapy is limited. We assessed the 6-month effect of glatiramer acetate on MS-related fatigue in patients switching from interferon-beta (IFN-beta) in clinical practice. METHODS: This was an observational study including 54 patients with relapsing-remitting MS that showed moderate/severe fatigue primarily caused by MS before switching from IFN-beta to glatiramer acetate and received glatiramer acetate for >=6 months in daily practice. Study data were retrospectively collected through chart review at treatment switch and over the following 6 months on glatiramer acetate. RESULTS: Over the 6-month administration of glatiramer acetate, scores on the Modified Fatigue Impact Scale decreased: overall (p < 0.001), physical scale (p < 0.001), cognitive scale (p < 0.001), and psychosocial scale (p < 0.001). The Work Productivity and Activity Impairment Questionnaire showed improvements in work (p = 0.009) and other daily activity impairment (p < 0.001). Health-related quality of life as per the Multiple Sclerosis Impact Scale also improved: physical score (p < 0.001) and psychological score (p < 0.001). CONCLUSION: Patients with moderate/severe fatigue switching from IFN-beta to glatiramer acetate may benefit from fatigue improvements that contribute to reduce their work/activity impairment and improve their quality of life. PMID- 27376846 TI - The effects of environmental and socioeconomic factors on land-use changes: a study of Alberta, Canada. AB - Various environmental and socioeconomic issues have been attributed to land-use changes, and therefore, the underlying mechanisms merit investigation and quantification. This study assesses a comprehensive series of land-use conversions that were implemented over a recent 12-year period in the province of Alberta, Canada, where rapid economic and population growth has occurred. Spatial autocorrelation models are applied to identify the comprehensive effects of environmental and socioeconomic factors in each conversion case. The empirical results show that the impacts of key environmental and socioeconomic factors varied in intensity depending on the type of land-use conversion involved. Overall, land suitability for agricultural uses, road density, elevation, and population growth were found to be significant predictors of land-use changes. High land suitability, low elevation, and moderate road density were associated with land conversion for agricultural purposes. PMID- 27376847 TI - Analysis of land suitability for urban development in Ahwaz County in southwestern Iran using fuzzy logic and analytic network process (ANP). AB - The ever-increasing development of cities due to population growth and migration has led to unplanned constructions and great changes in urban spatial structure, especially the physical development of cities in unsuitable places, which requires conscious guidance and fundamental organization. It is therefore necessary to identify suitable sites for future development of cities and prevent urban sprawl as one of the main concerns of urban managers and planners. In this study, to determine the suitable sites for urban development in the county of Ahwaz, the effective biophysical and socioeconomic criteria (including 27 sub criteria) were initially determined based on literature review and interviews with certified experts. In the next step, a database of criteria and sub-criteria was prepared. Standardization of values and unification of scales in map layers were done using fuzzy logic. The criteria and sub-criteria were weighted by analytic network process (ANP) in the Super Decision software. Next, the map layers were overlaid using weighted linear combination (WLC) in the GIS software. According to the research findings, the final land suitability map was prepared with five suitability classes of very high (5.86 %), high (31.93 %), medium (38.61 %), low (17.65 %), and very low (5.95 %). Also, in terms of spatial distribution, suitable lands for urban development are mainly located in the central and southern parts of the Ahwaz County. It is expected that integration of fuzzy logic and ANP model will provide a better decision support tool compared with other models. The developed model can also be used in the land suitability analysis of other cities. PMID- 27376848 TI - Epitaxial 2D PbS Nanoplates Arrays with Highly Efficient Infrared Response. AB - 2D nonlayered semiconductors attract intense interest due to their unique planar structure and various fascinating optoelectronic properties. Here, a method is developed to design orientation-controlled and well-defined single-crystalline PbS nanoplates arrays on mica. Furthermore, the single PbS nanoplate device displays great photoresponsivity, detectivity, and photogain values as high as 1621 A W-1 , 1.72 * 1011 Jones, and 2512, respectively. PMID- 27376849 TI - Poly(paraphenylene sulfide) and Poly(metaphenylene sulfide) via Light-Initiated SRN 1-Type Polymerization of Halogenated Thiophenols. AB - In this work, the synthesis of various halogenated thiophenol derivatives is presented. These thiophenols are used as monomers in light-initiated SRN 1-type radical polymerization reactions. The method provides easy access to industrially relevant poly(paraphenylene sulfide) and poly(metaphenylene sulfide). The influence of the halide leaving group and of other substituents in the thiophenol monomer on the polymerization process is investigated. PMID- 27376851 TI - [Update: Tuberculosis among adults in Germany]. PMID- 27376850 TI - The vaginal vestibule: assessing the case for an anterior and posterior division. AB - The vaginal vestibule has not been the subject of a dedicated journal article. Recent terminology has suggested its division into anterior and posterior components. The case for this division has not yet been assessed. Both components extend laterally from the hymen to the junction with the labia minora. The posterior vaginal vestibule is proposed to extend from the posterior aspect of the hymen to the anterior edge of the perineum whilst the anterior vestibule extends from the posterior aspect of the hymen to just below the clitoris. Anatomical considerations (differing layers) might firstly support the above division. The posterior vestibule, by necessity, is far more flexible with the superficial aspect (approximately 1.5 cm), anatomically and histologically, comprising skin and subcutaneous tissue, with perineal musculature deep to this. In turn, it is more likely to be subject to obstetric and surgical considerations than the anterior vaginal vestibule. Obstetric trauma, in particular, would tend to create defects, particularly at its posterior margin. Many dermatological and microbiological considerations may be common to both anterior and posterior vestibule. Any dermatological condition of the vestibule can result in sexual dysfunction and can be complicated by secondary muscular spasm. Congenital anomalies will differ anteriorly and posteriorly. Multiple considerations can be identified to support the case for division of the vaginal vestibule into anterior and posterior components. Neurourol. Urodynam. 36:979-983, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27376852 TI - A novel compound 2-(4-{2-[(phenylthio)acetyl]carbonohydrazonoyl}phenoxy)acetamide downregulates TSLP through blocking of caspase-1/NF-kappaB pathways. AB - Thymic stromal lymphopoietin (TSLP) is regarded as the main factor responsible for the pathogenesis of allergic disorders such as atopic dermatitis, chronic obstructive pulmonary diseases, and allergic rhinitis. As part of our continuing search for novel anti-inflammatory compounds, 2-(4-{2 [(phenylthio)acetyl]carbonohydrazonoyl}phenoxy)acetamide (PA) was analyzed. In the present study, we examined how PA regulates the mRNA expression and production of TSLP in the human mast cell line, HMC-1 cells. Computer-aided docking simulation, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, caspase-1 assay, and Western blotting were used to investigate the effects of PA. PA decreased the mRNA expression and production of TSLP in HMC 1 cells. PA (1MUM) inhibited the TSLP production up to 87.710+/-5.201%. PA also improved the activation and phosphorylation of nuclear factor-kappaB as well as the degradation and phosphorylation of IkappaBalpha. Caspase-1 activation was up regulated in activated HMC-1 cells, whereas caspase-1 activation was down regulated by PA. Finally, PA inhibited ear swelling response induced by phorbol myristate acetate in mice. These results indicate that PA would be effective to treat inflammatory and atopic disorders through the down-regulations of TSLP. PMID- 27376853 TI - Berberine alleviates postoperative cognitive dysfunction by suppressing neuroinflammation in aged mice. AB - Postoperative cognitive dysfunction (POCD) is a significant cause of morbidity after surgery, especially for the elderly. Accumulating evidence has demonstrated that neuroinflammation plays a key role in the pathogenesis of POCD. Thus, we hypothesized that berberine, an isoquinoline alkaloid with anti-inflammatory effects, could improve surgery-induced cognitive impairment. Twenty-month-old male C57BL/6 mice were subjected to exploratory laparotomy with isoflurane anesthesia to mimic the clinical human abdominal surgery. For the interventional studies, mice received berberine (10mg/kg) or vehicle intraperitoneally. For the in vitro study, we examined the effects of berberine on lipopolysaccharide (LPS) induced inflammatory mediators by cultured BV2 cells. Behavioral tests, expressions of IBA1, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 were performed at the indicated time points. In the present study, we showed that surgery impaired the contextual fear memory, as evidenced by the significantly decreased freezing time to the context. This behavioral change coincided with marked increases in IBA1, TNF-alpha, IL-1beta, and IL-6 in the prefrontal cortex and hippocampus only at 24h but not 7 d after surgery. In BV2 cells, LPS induced significantly increased TNF-alpha and IL-1beta expressions. Notably, berberine treatment rescued surgery-induced cognitive impairment and inhibited the release of IBA1, IL-1beta, and IL-6 in the hippocampus. In line with the in vivo study, berberine treatment suppressed LPS stimulated production of TNF-alpha and IL-1beta in BV2 cells. In conclusion, our study suggests that berberine could alleviate POCD by suppressing neuroinflammation in aged mice. PMID- 27376854 TI - Potentiation of indomethacin-induced anti-inflammatory response by pioglitazone in carrageenan-induced acute inflammation in rats: Role of PPARgamma receptors. AB - This study aimed to assess the interaction between anti-inflammatory effects of pioglitazone (peroxysome proliferator activated receptor-gamma (PPARgamma) agonist, PGL), and indomethacin (cyclooxygenase (COX) inhibitor, IND) and to evaluate the possible underlying mechanisms. Paw edema induced by carrageenan was used to induce inflammation. Different doses of IND (0.3-10mg/kg) and PGL (1 20mg/kg) alone or in combination were administered intraperitoneally to rats. Paw tissue levels of PPARgamma, COX-2, and prostaglandin E2 and serum levels of TNF alpha and IL-10 were also estimated. Doses of IND and PGL showed a statistically significant anti-inflammatory effect. Combination of a non-effective dose of IND (0.3mg/kg) with increasing doses of PGL (1-10mg/kg) resulted in potentiated anti inflammation and vise versa. IND, PGL and the combination were able to reduce the COX-2, PGE2 contents and TNF-alpha level. Moreover, all these treatments caused elevation in PPARgamma levels and IL-10 levels. However, when the rats were pre treated with GW-9662 (a selective PPARgamma antagonist), all the anti inflammation and alterations in the biochemical factors were antagonized. These results showed that PGL markedly enhanced the anti-inflammatory activity of IND and this effect mediated partly at least, through PPARgamma. Possible mechanisms of the interaction were that PGL stimulates the PPARgamma and inhibits COX-2 by those cytokines that trigger the PPARgamma and also inhibit COX-2. This study suggests that combination therapy with pioglitazone and indomethacin may provide an alternative for the clinical control of inflammation especially in patients with diabetes. PMID- 27376855 TI - Species difference in reactivity to lignin-like enzymatically polymerized polyphenols on interferon-gamma synthesis and involvement of interleukin-2 production in mice. AB - Recent studies have revealed that lignin-like polymerized polyphenols can activate innate immune systems. In this study, we aimed to evaluate whether these polymerized polyphenols could activate leukocytes from different murine strains. Splenocytes from 12 mouse strains were investigated. Our results revealed species differences in reactivity to phenolic polymers on interferon-gamma (IFN-gamma) release. Mice that possessed the H2(a) or H2(k) haplotype antigens were the highly responsive strains. To clarify these different points in soluble factors, multiplex cytokine profiling analysis was carried out and we identified interleukin (IL)-2 as a key molecule for IFN-gamma induction by polymerized polyphenols. Furthermore, inhibition of IL-2 and IL-2Ralpha by neutralizing antibodies significantly decreased cytokine production in the highly responsive mice strains. Our results indicate that species difference in reactivity to phenolic polymers is mediated by adequate release of IL-2 and its receptor, IL 2Ralpha. PMID- 27376856 TI - Systematic determination of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in outdoor jackets. AB - Sixteen outdoor jackets were purchased in 2011/12 and analyzed for 23 different perfluoroalkyl and polyfluoroalkyl substances (PFASs). The jackets were selected based on their origin of production, price, market, and textile, such as polyester, nylon, polyamide, and content of poly(tetrafluoroethylene) membranes. Two robust analytical methods based on high pressure liquid chromatography combined with tandem mass spectrometry, as well as two liquid extractions, were developed enabling the analysis of PFASs with widely different physico-chemical properties. The jackets were found to contain PFASs in a range between 0.03 and 719 MUg/m(2). Perfluorooctanoic acid (PFOA) was omnipresent (0.02-171 MUg/m(2)), although at lower concentrations compared to the precursors of perfluoroalkyl carboxylic acids (PFCAs), namely fluorotelomer alcohols (FTOHs) (<0.001-698 MUg/m(2)). Perfluoroalkane sulfonic acids and their putative precursors, in particular perfluoroalkane sulfonamides, were detected much less frequently at concentrations up to 5 MUg/m(2). To determine the effect of the volatility of FTOHs, four selected jackets were stored in a sealed bag in the dark at room temperature and re-analyzed after 3.5 years. Only 10%-20% of the initial concentration of 8:2-FTOH and 20%-50% of 10:2-FTOH were found, whereas the concentrations of PFOA and perfluorodecanoic acid increased significantly. This supports the hypothesis that PFAS concentrations in textiles are also strongly dependent on age, and conditions of transport and storage. PMID- 27376857 TI - Environmental risk assessment of Polish wastewater treatment plant activity. AB - Wastewater treatment plants (WWTPs) play an extremely important role in shaping modern society's environmental well-being and awareness, however only well operated and supervised systems can be considered as environmentally sustainable. For this reason, an attempt was undertaken to assess the environmental burden posed by WWTPs in major Polish cities by collecting water samples prior to and just after wastewater release points. Both classical and biological methods (Microtox((r)), Ostracodtoxkit FTM and comet assay) were utilized to assess environmental impact of given WWTP. Interestingly, in some cases, water quality improvement indicated as a toxicity decrement toward one of the bio-indicating organisms makes water worse for others in the systems. This fact is particularly noticeable in case of Silesian cities where heavy industry and high population density is present. It proves that WWTP should undergo individual evaluation of pollutant removal efficiency and tuned to selectively remove pollutants of highest risk to surrounding regional ecosystems. Biotests again proved to be an extremely important tool to fully assess the impact of environmental stressors on water bodies receiving effluents from WWTPs. PMID- 27376858 TI - Influences of NOM composition and bacteriological characteristics on biological stability in a full-scale drinking water treatment plant. AB - The influences of natural organic matter (NOM) and bacteriological characteristics on the biological stability of water were investigated in a full scale drinking water treatment plant. We found that prechlorination decreased the hydrophobicity of the organic matter and significantly increased the high molecular-weight (MW) dissolved organic matter, such as biopolymers and humic substances. High-MW organic matter and structurally complex compounds are known to be relatively slowly biodegradable; however, because of the prechlorination step, the indigenous bacteria could readily utilise these fractions as assimilable organic carbon. Sequential coagulation and sedimentation resulted in the substantial removal of biopolymer (74%), humic substance (33%), bacterial cells (79%), and assimilable organic carbon (67%). Rapid sand and granular activated carbon filtration induced an increase in the low-nucleic-acid content bacteria; however, these bacteria were biologically less active in relation to enzymatic activity and ATP. The granular activated carbon step was essential to securing biological stability (the ability to prevent bacterial growth) by removing the residual assimilable organic carbon that had formed during the ozone treatment. The growth potential of Escherichia coli and indigenous bacteria were found to differ in respect to NOM characteristics. In comparison with E. coli, the indigenous bacteria utilised a broader range of NOM as a carbon source. Principal component analysis demonstrated that the measured biological stability of water could differ, depending on the NOM characteristics, as well as on the bacterial inoculum selected for the analysis. PMID- 27376859 TI - Elevated CO2 affects secondary metabolites in Robinia pseudoacacia L. seedlings in Cd- and Pb-contaminated soils. AB - Secondary metabolites play important roles in plant interactions with the environment. The co-occurrence of heavy metal contamination of soils and rising atmospheric CO2 has important effects on plant. It is important to explore the ways in which production of plant secondary metabolites is affected by heavy metals under elevated atmospheric CO2. We examined the effects of elevated CO2 on secondary metabolite contents in Robinia pseudoacacia seedlings grown in Cd- and lead (Pb)-contaminated soils. The increase in secondary metabolites was greater under Cd + Pb exposure than under exposure to individual metals regardless of elevated CO2 with the exception of condensed tannins in leaves and total alkaloids in stems. Except for phenolic compounds and condensed tannins, elevated CO2 was associated with increased secondary metabolite contents in leaves and stems of plants exposed to Cd, Pb, and Cd + Pb compared to plants exposed to ambient CO2 + metals. Changes in saponins in leaves and alkaloids in stems were greater than changes in the other secondary metabolites. Significant interactive effects of CO2, Cd, and Pb on secondary metabolites were observed. Saponins in leaves and alkaloids in stems were more sensitive than other secondary metabolites to elevated CO2 + Cd + Pb. Elevated CO2 could modulate plant protection and defense mechanisms in R. pseudoacacia seedlings exposed to heavy metals by altering the production of secondary metabolites. The increased Cd and Pb uptake under elevated CO2 suggested that R. pseudoacacia may be used in the phytoremediation of heavy metal-contaminated soils under global environmental scenarios. PMID- 27376860 TI - Determination of illicit drugs in aqueous environmental samples by online solid phase extraction coupled to liquid chromatography-tandem mass spectrometry. AB - In this study, a fully automated analytical method, based on online solid phase extraction coupled to liquid chromatography-triple quadrupole tandem mass spectrometry (online SPE-LC-MS/MS), has been developed and optimized for the quantification of 10 illicit drugs and metabolites in environmentally aqueous samples collected from China. The particular attention was devoted to minimize the matrix effects through a washing step, which washed out the interferences effectively and helped to reduce the matrix effect significantly. The key advantages of the method are high sensitivity, selectivity and reliability of results, smaller sample manipulation, full automation, and fairly high throughput. The whole procedure was then successfully applied in the analysis of various surface water and wastewater effluents samples. Pseudoephedrine have been detected at trace levels (several tens ng L(-1) or less), while MDA, MDMA, benzoylecgonine and methadone were below the LOQ in all samples. Caffeine, cotinine and paraxanthine, which may be derived from medicines and foods, were detected with the highest frequencies and concentrations. PMID- 27376861 TI - Acidification and sulfide formation control during reductive dechlorination of 1,2-dichloroethane in groundwater: Effectiveness and mechanistic study. AB - To enhance the reductive dechlorination of 1,2-dichloroethane (DCA) in groundwater, substrate injection may be required. However, substrate biodegradation causes groundwater acidification and sulfide production, which inhibits the bacteria responsible for DCA dechlorination and results in an odor problem. In the microcosm study, the effectiveness of the addition of ferrous sulfate (FS), desulfurization slag (DS), and nanoscale zero-valent iron (nZVI) on acidification and sulfide control was studied during reductive dechlorination of DCA, and the emulsified substrate (ES) was used as the substrate. Up to 94% of the sulfide was removed with FS and DS addition (0.25 wt%) (initial DCA concentration = 13.5 mg/L). FS and DS amendments resulted in the formation of a metal sulfide, which reduced the hydrogen sulfide concentration as well as the subsequent odor problem. Approximately 96% of the DCA was degraded under reductive dechlorination with nZVI or DS addition using ES as the substrate. In microcosms with nZVI or DS addition, the sulfide concentration was reduced to less than 15 MUg/L. Acidification can be controlled via hydroxide ions production after nZVI oxidation and reaction of free CaO (released from DS) with water, which enhanced DCA dechlorination. The quantitative polymerase chain reaction results confirmed that the microcosms with nZVI added had the highest Dehalococcoides population (up to 2.5 * 10(8) gene copies/g soil) due to effective acidification control. The alpha-elimination mechanism was the main abiotic process, and reductive dechlorination dominated by Dehalococcides was the biotic mechanism that resulted in DCA removal. More than 22 bacterial species were detected, and dechlorinating bacteria existed in soils under alkaline and acidic conditions. PMID- 27376862 TI - Childhood maltreatment and attention deficit hyperactivity disorder symptoms in adults: a large twin study. AB - BACKGROUND: Childhood maltreatment (CM) has been associated with increased risk of attention deficit hyperactivity disorder (ADHD) in children and adults. It is, however, unclear whether this association is causal or due to familial confounding. METHOD: Data from 18 168 adult twins, aged 20-46 years, were drawn from the population-based Swedish twin registry. Retrospective self-ratings of CM (emotional and physical neglect, physical and sexual abuse and witnessing family violence), and self-ratings for DSM-IV ADHD symptoms in adulthood were analysed. Possible familial confounding was investigated using a within twin-pair design based on monozygotic (MZ) and dizygotic (DZ) twins. RESULTS: CM was significantly associated with increased levels of ADHD symptom scores in adults [regression coefficient: 0.40 standard deviations, 95% confidence interval (CI) 0.37-0.43]. Within twin-pair analyses showed attenuated but significant estimates within DZ (0.29, 95% CI 0.21-0.36) and MZ (0.18, 95% CI 0.10-0.25) twin pairs. Similar results emerged for hyperactive/impulsive and inattentive ADHD symptom scores separately in association with CM. We conducted sensitivity analyses for early maltreatment, before age 7, and for abuse and neglect separately, and found similarly reduced estimates in DZ and MZ pairs. Re-traumatization after age 7 did not significantly influence results. CONCLUSIONS: CM was significantly associated with increased ADHD symptoms in adults. Associations were partly due to familial confounding, but also consistent with a causal interpretation. Our findings support cognitive neuroscience studies investigating neural pathways through which exposure to CM may influence ADHD. Clinicians treating adults with ADHD should be aware of the association with maltreatment. PMID- 27376863 TI - Integrative concepts of rosacea pathophysiology, clinical presentation and new therapeutics. AB - Rosacea is a chronic relapsing inflammatory skin disease with high prevalence worldwide. Recent research suggests that dysregulation of innate and adaptive immune pathways as well as neurovascular changes is present, with different degrees of importance in the various subtypes. Neither the aetiology, genetics nor pathophysiological basis of the vascular, inflammatory or fibrotic changes is well understood. The clinical spectrum comprises a huge variability from erythema (vasodilation) to papules/pustules (inflammatory infiltrate) to phymata (fibrosis, glandular hyperplasia) making it a valuable human disease model to understand the interplay between the neurovascular and immune systems as well as the progression from chronic inflammation to fibrosis in skin. The lack of appropriate animal models emphasizes the importance of further translational research validating observed molecular pathways under disease conditions. A wide spectrum of physical (UV, temperature), biological (microbiota, food) and endogenous (genetic, stress) stimuli has been discussed as "trigger factors" of rosacea. Novel findings implicate keratinocytes, smooth muscle cells, endothelial cells, macrophages, mast cells, fibroblasts, Th1/Th17 cells, antibody-producing B cells and neurons in the pathobiology of rosacea. So far, pattern recognition receptors like TLR2, transient receptor potential ion channels, cytokines, chemokines and proteases have been implicated as critical receptors/mediators. However, our understanding of the interactive networks on the molecular level is very limited. Identification of critical molecular components of the inflammatory cascade including antimicrobial peptides, the IL-1beta inflammasome, TNF, IFN gamma, proteases and neuropeptides may provide the basis for novel pathomechanism based therapeutic approaches for this frequent and bothersome skin disease. PMID- 27376864 TI - Perceived benefits following completion of a clinical dermatology online programme for general practitioners. PMID- 27376865 TI - Toward translating near-infrared spectroscopy oxygen saturation data for the non invasive prediction of spatial and temporal hemodynamics during exercise. AB - Image-based computational fluid dynamics (CFD) studies conducted at rest have shown that atherosclerotic plaque in the thoracic aorta (TA) correlates with adverse wall shear stress (WSS), but there is a paucity of such data under elevated flow conditions. We developed a pedaling exercise protocol to obtain phase contrast magnetic resonance imaging (PC-MRI) blood flow measurements in the TA and brachiocephalic arteries during three-tiered supine pedaling at 130, 150, and 170 % of resting heart rate (HR), and relate these measurements to non invasive tissue oxygen saturation [Formula: see text] acquired by near-infrared spectroscopy (NIRS) while conducting the same protocol. Local quantification of WSS indices by CFD revealed low time-averaged WSS on the outer curvature of the ascending aorta and the inner curvature of the descending aorta (dAo) that progressively increased with exercise, but that remained low on the anterior surface of brachiocephalic arteries. High oscillatory WSS observed on the inner curvature of the aorta persisted during exercise as well. Results suggest locally continuous exposure to potentially deleterious indices of WSS despite benefits of exercise. Linear relationships between flow distributions and tissue oxygen extraction calculated from [Formula: see text] were found between the left common carotid versus cerebral tissue [Formula: see text] and the dAo versus leg tissue [Formula: see text]. A resulting six-step procedure is presented to use NIRS data as a surrogate for exercise PC-MRI when setting boundary conditions for future CFD studies of the TA under simulated exercise conditions. Relationships and ensemble-averaged PC-MRI inflow waveforms are provided in an online repository for this purpose. PMID- 27376866 TI - Infant patterns of reactivity to tactile stimulation during parent-child interaction. AB - Touch is the primary modality infants use to engage with the world; atypical responses to tactile stimuli may indicate risk for disordered outcomes. The current study examined infants' responses to tactile stimulation within parent child interaction, adding to prior knowledge based on parent report. Nine-month old infants (N=497) were observed while parents painted and pressed infants' hands and feet to paper to make designs. Positive and negative affect and gazing away, exploring, and resistance behaviors were coded. Latent Class Analysis of observed behaviors yielded four tactile response patterns partially consistent with current nosology for sensory processing patterns: Low Reactive, Sensory Overreactive, Sensory Seeking, and Mixed Over/Underreactive. To evaluate whether patterns made valid distinctions among infants, latent classes were examined in relation to parent-reported temperament. Infants in the Mixed Over/Underreactive class were rated higher in distress to limitations and activity level than other infants. Sensory processing patterns observed in parent-child interaction are consistent with those identified by parent-report and may be used in future research to elucidate relations with temperament and typical and atypical development. PMID- 27376867 TI - Design and Rationale of 'Tackling Acute Kidney Injury', a Multicentre Quality Improvement Study. AB - Acute kidney injury (AKI) is common and associated with extremely poor outcomes. While strategies to tackle deficiencies in basic care delivery are advocated, robust testing of their effectiveness is also needed. The Tackling AKI study was designed to test whether a complex intervention (consisting of an e-alert, care bundle and education programme) can be successfully implemented across a range of UK hospitals, and whether this will deliver improved patient outcomes. This multicentre, pragmatic clinical trial will employ a cluster randomised stepped wedge design to study this in all adult patients who sustain AKI in the 5 participating hospitals over a 2-year period. The intervention will be supported by a comprehensive change management framework. Data collection will include patient outcomes, process measures and a qualitative assessment of barriers and enablers to implementation. This article describes the rationale and design behind the Tackling AKI study. (c) 2016 S. Karger AG, Basel. PMID- 27376868 TI - Enuresis and Punishment: The Adverse Effects on Child Development and on Treatment. AB - OBJECTIVE: To investigate the role of punishment in enuretic children and how the punishments can influence therapy response. METHODS: We enrolled 218 enuretic children. The children and their families were asked to participate in the study at the end of the clinical evaluation. RESULTS: The analysis of the questionnaires shows that at least one punishment because of nocturnal enuresis (NE) had been applied to 27 out of 218 (12.4%) children. Punishment methods were reprimanding in 19 out of 27 (70.4%), depriving of sleep in 11 out of 27 (40.7%), mildly beating in 3 out of 27 (11.1%), leaving the child wet in 1 out of 27 (3.7%) and other methods in 2 out of 27 (7.4%). In the group of punished children, a full or partial response in terms of a decreased number of wet nights was achieved in 40.7 vs. 59.2% in children who had not been punished. CONCLUSIONS: Parents should be sensitized on the adverse effects of punishment on child development. It is important in childcare to explain the definitions of the disorder and find the best treatment (behavioural and/or medicinal) depending on the single patient, his/her family and compliance of both. Successful management of NE has benefits to both the child and the family. PMID- 27376869 TI - Source insights into the 11-h daytime and nighttime fine ambient particulate matter in China as well as the synthetic studies using the new Multilinear Engine 2-species ratios (ME2-SR) method. AB - Modeled results are very important for environmental management. Unreasonable modeled result can lead to wrong strategy for air pollution management. In this work, an improved physically constrained source apportionment (PCSA) technology known as Multilinear Engine 2-species ratios (ME2-SR) was developed to the 11-h daytime and nighttime fine ambient particulate matter in urban area. Firstly, synthetic studies were carried out to explore the effectiveness of ME2-SR. The estimated source contributions were compared with the true values. The results suggest that, compared with the positive matrix factorization (PMF) model, the ME2-SR method could obtain more physically reliable outcomes, indicating that ME2 SR was effective, especially when apportioning the datasets with no unknown source. Additionally, 11-h daytime and nighttime PM2.5 samples were collected from Tianjin in China. The sources of the 11-h daytime and nighttime fine ambient particulate matter in China were identified using the new method and the PMF model. The calculated source contributions for ME2-SR for daytime PM2.5 samples are resuspended dust (38.91 MUg m(-3), 26.60%), sulfate and nitrate (38.60 MUg m( 3), 26.39%), vehicle exhaust and road dust (38.26 MUg m(-3), 26.16%) and coal combustion (20.14 MUg m(-3), 13.77%), and those for nighttime PM2.5 samples are resuspended dust (18.78 MUg m(-3), 12.91%), sulfate and nitrate (41.57 MUg m(-3), 28.58%), vehicle exhaust and road dust (38.39 MUg m(-3), 26.39%), and coal combustion (36.76 MUg m(-3), 25.27%). The comparisons of the constrained versus unconstrained outcomes clearly suggest that the physical meaning of the ME2-SR results is interpretable and reliable, not only for the specified species values but also for source contributions. The findings indicate that the ME2-SR method can be a useful tool in source apportionment studies, for air pollution management. PMID- 27376870 TI - To manage inland fisheries is to manage at the social-ecological watershed scale. AB - Approaches to managing inland fisheries vary between systems and regions but are often based on large-scale marine fisheries principles and thus limited and outdated. Rarely do they adopt holistic approaches that consider the complex interplay among humans, fish, and the environment. We argue that there is an urgent need for a shift in inland fisheries management towards holistic and transdisciplinary approaches that embrace the principles of social-ecological systems at the watershed scale. The interconnectedness of inland fisheries with their associated watershed (biotic, abiotic, and humans) make them extremely complex and challenging to manage and protect. For this reason, the watershed is a logical management unit. To assist management at this scale, we propose a framework that integrates disparate concepts and management paradigms to facilitate inland fisheries management and sustainability. We contend that inland fisheries need to be managed as social-ecological watershed system (SEWS). The framework supports watershed-scale and transboundary governance to manage inland fisheries, and transdisciplinary projects and teams to ensure relevant and applicable monitoring and research. We discuss concepts of social-ecological feedback and interactions of multiple stressors and factors within/between the social-ecological systems. Moreover, we emphasize that management, monitoring, and research on inland fisheries at the watershed scale are needed to ensure long term sustainable and resilient fisheries. PMID- 27376871 TI - Patient-reported outcome after radical cystectomy: translation and psychometric validation of the Swedish version of the Functional Assessment of Cancer Therapy Scale Vanderbilt Cystectomy Index. AB - OBJECTIVE: The aim of this study was to translate and validate the Swedish version of the Functional Assessment of Cancer Therapy Scale - Vanderbilt Cystectomy Index (FACT-VCI). MATERIALS AND METHODS: For adaptation into Swedish, a multiprofessional team was used for translation including cultural adjustment, followed by back-translation. Test and retest in 10 individuals was followed by assessing metric properties in 75 consecutive patients with bladder cancer treated with radical cystectomy. Reliability and internal consistency were measured by Cronbach's alpha. Face validity was tested with two laypersons and construct validity was tested by correlation to the dimensions in the Functional Assessment of Cancer Therapy Scale - General (FACT-G). RESULTS: The translated Swedish instrument showed validity and reliability similar to the original, and the results were comparable to published studies using FACT-VCI. The correlation between the VCI sum score and FACT-G dimensions was significant in all dimensions and the item-total correlation was over 0.3; therefore, the construct validity was acceptable. In addition, it was possible to detect differences in separate items in the translated version of FACT-VCI between age groups, type of diversion and those treated with chemotherapy, even though the samples were small. CONCLUSIONS: The Swedish version of FACT-VCI is a valid and reliable instrument for use in the follow-up of patients with bladder cancer treated with urinary diversion. To measure changes after surgery, preoperative assessment with the related FACT-G instrument is advisable. PMID- 27376872 TI - Efficacy and safety of retigabine/ezogabine as adjunctive therapy in adult Asian patients with drug-resistant partial-onset seizures: A randomized, placebo controlled Phase III study. AB - PURPOSE: The purpose of this study was to evaluate the efficacy and safety of adjunctive retigabine/ezogabine (RTG/EZG) therapy in Asian adults with partial onset seizures. METHODS: A Phase III, randomized, double-blind, placebo controlled, parallel-group study was conducted at 26 centers in Asia. Eligible patients were randomized in a 1:1:1 ratio to receive RTG/EZG 600mg/day (200mg 3 times daily), RTG/EZG 900mg/day (300mg 3 times daily), or placebo. The study consisted of an 8-week screening/baseline phase, followed by a 16-week treatment phase (4-week titration phase and 12-week maintenance phase). RESULTS: The study was terminated early because of emerging safety information on RTG/EZG (i.e., retinal pigmentation and skin/mucosal discoloration) from long-term trials. Of 132 patients screened and 76 randomized, 75 (placebo, n=25; RTG/EZG 600mg/day, n=26; RTG/EZG 900mg/day, n=24) received at least 1 dose of the study drug and were included in the safety and intent-to-treat populations. The responder rate (>=50% reduction in 28-day total partial-onset seizure frequency) was 31% with RTG/EZG 600mg/day and 17% with RTG/EZG 900mg/day versus 0% with placebo. Median percent change from baseline in 28-day total partial-onset seizure frequency during the maintenance phase was -33.90% and -22.46% with RTG/EZG 600 and 900mg/day, respectively, versus -22.21% with placebo. No new safety concerns were identified. CONCLUSIONS: Insufficient data were obtained to permit definitive conclusions. However, the results appear to be broadly in line with those from previous studies that included primarily Caucasian patients. PMID- 27376873 TI - Deformation-Induced Martensite: A New Paradigm for Exceptional Steels. AB - Martensite steel is induced from pearlitic steel by a newly discovered method, which is completely different from the traditional route of quenching austenitic steel. Both experimental and theoretical studies demonstrate that Fe-C martensite forms by severe deformation at room temperature. The new mechanism identified here opens a paths to material-design strategies based on deformation-driven nanoscale phase transformations. PMID- 27376874 TI - Genomics of human fatty liver disease reveal mechanistically linked lipid droplet associated gene regulations in bland steatosis and nonalcoholic steatohepatitis. AB - Nonalcoholic fatty liver disease (NAFLD) is a common disorder hallmarked by excessive lipid deposits. Based on our recent research on lipid droplet (LD) formation in hepatocytes, we investigated LD-associated gene regulations in NAFLD of different grades, that is, steatosis vs steatohepatitis by comparing liver biopsies from healthy controls (N = 13) and NAFLD patients (N = 102). On average, more than 700 differentially expressed genes (DEGs) were identified of which 146 are mechanistically linked to LD formation. We identified 51 LD-associated DEGs frequently regulated in patient samples (range >=5 to <=102) with the liver receptor homolog-1(NR5A2), that is, a key regulator of cholesterol metabolism being commonly repressed among 100 patients examined. With bland steatosis, notable regulations involved hypoxia-inducible lipid droplet-associated-protein and diacylglycerol-O-acyltransferase-2 renowned for their role in LD-growth. Conversely, nonalcoholic steatohepatitis-associated DEGs coded for epidermal growth factor receptor and TLR4 signaling with decreased expression of the GTPase Rab5 and the lipid phosphohydrolase PPAP2B thus highlighting adaptive responses to inflammation, LDL-mediated endocytosis and lipogenesis, respectively. Studies with steatotic primary human hepatocyte cultures demonstrated induction of LD associated PLIN2, CIDEC, DNAAF1, whereas repressed expression of CPT1A, ANGPTL4, and PKLR informed on burdened mitochondrial metabolism. Equally, repressed expression of the B-lymphocyte chemoattractant CXCL13 and STAT4 as well as induced FGF21 evidenced amelioration of steatosis-related inflammation. In vitro/in-vivo patient sample comparisons confirmed C-reactive protein, SOCS3, NR5A2, and SOD2 as commonly regulated. Lastly, STRING network analysis highlighted potential "druggable" targets with PLIN2, CIDEC, and hypoxia inducible lipid droplet-associated-protein being confirmed by immunofluorescence microscopy. In conclusion, steatosis and steatohepatitis specific gene regulations informed on the pathogenesis of NAFLD to broaden the perspective of targeted therapies. PMID- 27376875 TI - The role of autosuggestion in geriatric patients' quality of life: a study on psycho-neuro-endocrine-immunology pathway. AB - BACKGROUND: There has been no study conducted about the effect of autosuggestion on quality of life for geriatric patients. Our aim was to evaluate the efficacy of autosuggestion for geriatric patients' quality of life and its impact on psycho-neuro-endocrine-immune pathway. METHODS: Sixty geriatric patients aged >=60 years in a ward were randomly assigned to either receive autosuggestion or not. Autosuggestion was recorded in a tape to be heard daily for 30 days. Both groups received the standard medical therapy. Primary outcome was quality of life by COOP chart. Secondary outcomes were serum cortisol level, interleukin-2, interleukin-6, interferon-gamma, and N-acetylaspartate/creatine ratio in limbic/paralimbic system by magnetic resonance spectroscopy. The study was single blinded due to the nature of the intervention studied. RESULTS: Out of 60 subjects, 51 finished the study. The autosuggestion group reported better scores than the control one for quality of life, COOP chart 1.95 vs. 2.22 (95% CI, p = 0.02). There were increments of serum cortisol (p = 0.03) and interleukin-6 in the autosuggestion group (p = 0.04). Interleukin-2, interferon-gamma, and N acetylaspartate/creatine ratio in prefrontal cortex showed a tendency to increase in the autosuggestion groups. CONCLUSION: Autosuggestion is associated with improvement of geriatrics' quality of life, serum cortisol level, and adaptive immunity. There is a better trend for neuroplasticity in prefrontal cortex in the autosuggestion group. PMID- 27376876 TI - The effect of fatigue on the corrosion resistance of common medical alloys. AB - The effect of mechanical fatigue on the corrosion resistance of medical devices has been a concern for devices that experience significant fatigue during their lifespan and devices made from metallic alloys. The Food and Drug Administration had recommended in some instances for corrosion testing to be performed on post fatigued devices [Non-clinical tests and recommended labeling for intravascular stents and associated delivery systems: guidance for industry and FDA staff. 2005: Food and Drug Administration, Center for Devices and Radiological Health], although the need for this has been debated [Nagaraja S, et al., J Biomed Mater Res Part B: Appl Biomater 2016, 8.] This study seeks to evaluate the effect of fatigue on the corrosion resistance of 5 different materials commonly used in medical devices: 316 LVM stainless steel, MP35N cobalt chromium, electropolished nitinol, mechanically polished nitinol, and black oxide nitinol. Prior to corrosion testing per ASTM F2129, wires of each alloy were split into subgroups and subjected to either nothing (that is, as received); high strain fatigue for less than 8 min; short-term phosphate buffered saline (PBS) soak for less than 8 min; low strain fatigue for 8 days; or long-term PBS soak for 8 days. Results from corrosion testing showed that the rest potential trended to an equilibrium potential with increasing time in PBS and that there was no statistical (p > 0.05) difference in breakdown potential between the fatigued and matching PBS soak groups for 9 out of 10 test conditions. Our results suggest that under these nonfretting conditions, corrosion susceptibility as measured by breakdown potential per ASTM F2129 was unaffected by the fatigue condition. 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2019-2026, 2017. PMID- 27376877 TI - Anion recognition by a bidentate chalcogen bond donor. AB - Perfluoroaryl-substituted tellurophenes act as anion receptors through noncovalent chalcogen bonding interactions. Linking two tellurophenes through an ethynylene group results in a significant level of chelate cooperativity, thus demonstrating that chalcogen bonding can be used to achieve multidentate anion recognition. PMID- 27376878 TI - Gastro-intestinal basidiobolomycosis in a 2-year-old boy: dramatic response to potassium iodide. AB - Gastro-intestinal basidiobolomycosis (GIB) is a rare fungal infection caused by Basidiobolus ranarum. Treatment includes surgical resection and long-term antifungal therapy. A 2.5-year-old boy presented with a 10-day history of abdominal pain, fever and diarrhoea, and a palpable abdominal mass was detected. Resection was undertaken and histology confirmed basidiobolomycosis. Treatment with amphotericin B and itraconazole was commenced, but the infection progressed and spread to involve the intestines, liver, ribs and lung, and also the abdominal wall after 6 months, requiring four operative procedures. Because of unresponsiveness to amphotericin and itraconazole, oral potassium iodide was added which resulted in complete resolution of the infection. Potassium iodide is an essential component of the treatment of systemic B. ranarum. PMID- 27376879 TI - Four New Steroidal Glycosides, Protolinckiosides A - D, from the Starfish Protoreaster lincki. AB - Four new steroidal glycosides, protolinckiosides A - D (1 - 4, resp.), were isolated along with four previously known glycosides, 5 - 8, from the MeOH/EtOH extract of the starfish Protoreaster lincki. The structures of 1 - 4 were elucidated by extensive NMR and ESI-MS techniques as (3beta,4beta,5alpha,6beta,7alpha,15alpha,16beta,25S)-4,6,7,8,15,16,26 heptahydroxycholestan-3-yl 2-O-methyl-beta-d-xylopyranoside (1), (3beta,5alpha,6beta,15alpha,24S)-3,5,6,8,15-pentahydroxycholestan-24-yl alpha-l arabinofuranoside (2), sodium (3beta,6beta,15alpha,16beta,24R)-29-(beta-d galactofuranosyloxy)-6,8,16-trihydroxy-3-[(2-O-methyl-beta-d xylopyranosyl)oxy]stigmast-4-en-15-yl sulfate (3), and sodium (3beta,6beta,15alpha,16beta,22E,24R)-28-(beta-d-galactofuranosyloxy)-6,8,16 trihydroxy-3-[(2-O-methyl-beta-d-xylopyranosyl)oxy]ergosta-4,22-dien-15-yl sulfate (4). The unsubstituted beta-d-galactofuranose residue at C(28) or C(29) of the side chains was found in starfish steroidal glycosides for the first time. Compounds 1 - 4 significantly decreased the intracellular reactive oxygen species (ROS) content in RAW 264.7 murine macrophages at induction by proinflammatory endotoxic lipopolysaccharide (LPS) from E. coli. PMID- 27376880 TI - P2 receptors, microglial cytokines and chemokines, and neuropathic pain. AB - Neuropathic pain is a debilitating chronic pain and represents a major clinical challenge. The molecular and cellular mechanisms underlying its development and maintenance are not fully understood but involve abnormal excitability in the dorsal horn of the spinal cord. A growing body of evidence has shown that this aberrant excitability may be a consequence not merely of changes in neurons but rather of multiple alterations in microglia, which are resident macrophages in the central nervous system. This review highlights recent advances in our understanding of the mechanisms that underlie neuropathic pain caused by peripheral nerve injury, with a specific focus on purinergic signaling in spinal cord microglia. This provides convincing evidence for a crucial role for microglial purinergic signaling in the pathogenesis of neuropathic pain, and P2 receptors may be potential therapeutic targets for managing neuropathic pain. (c) 2016 Wiley Periodicals, Inc. PMID- 27376881 TI - The Saccharomyces cerevisiae response to stress caused by the herbicidal active substance alachlor requires the iron regulon transcription factor Aft1p. AB - In the Saccharomyces cerevisiae eukaryotic model, the induction of the iron regulon genes ARN1, FIT2 and CTH2 by growth-inhibitory concentrations of alachlor (ALA) was dependent on Aft1p expression. This transcription factor was found to be activated through its nuclear localization. The hypersensitivity of the aft1Delta mutant to ALA was abrogated by surplus exogenous iron, suggesting that the role of Aft1p in ALA tolerance may be associated with iron limitation under ALA stress. A transient decrease in the cellular iron content in the ALA-stressed cells supported this idea. In contrast to the upregulation of the nonreductive iron uptake genes ARN1 and FIT2 by ALA, the quantity of FET3 and FTR1 transcripts encoding the high-affinity iron uptake reductive pathway decreased. Yeast cells were apparently more sensitive to ALA when iron uptake occurred through the reductive pathway than when the nonreductive uptake of ferrichrome-bound ferric iron was dominant. On the other hand, the ALA hypersensitivity of the aft1Delta mutant was reversed by medium supplementation with glutathione or N-acetyl-L cysteine. The results are compatible with possible links between ALA toxicity and perturbations in metal and antioxidant homeostasis, which may be relevant for environmental microbes and higher eukaryotes in situations of inadvertent herbicide contamination. PMID- 27376882 TI - Associations between nicotine dependence, anhedonia, urgency and smoking motives. AB - Models of nicotine dependence have suggested that the association between urgency, a subconstruct of impulsivity, and smoking behaviors may be mediated by motivations. Motives that are driven by expectations that smoking will relieve negative affect or increase positive affect may be especially salient in persons who have depression symptoms such as anhedonia. Support for associations between symptoms of depression, urgency, and addiction has been found for alcohol dependence, but empirical analysis is lacking for an interactive effect of urgency and depression symptoms on nicotine dependence. The current study investigated relationships among the urgency facet of impulsivity, anhedonia, smoking motives, and nicotine dependence with secondary analyses of a sample of 1084 daily smokers using simultaneous moderation and multiple mediation analyses. The moderation analysis revealed that although urgency was significantly associated with smoking at average or higher levels of anhedonia, it was unrelated to smoking when few anhedonia symptoms were endorsed. Further, multiple mediation analyses revealed that the smoking motives of craving, cue exposure, positive reinforcement, and tolerance significantly mediated the relationship between urgency and nicotine dependence. Results suggest that models of alcohol addiction that include an interactive effect of urgency and certain symptoms of depression may be applied to nicotine dependence. Examination of the multiple mediational pathways between urgency and nicotine dependence suggests directions for intervention efforts. PMID- 27376884 TI - Active site densities, oxygen activation and adsorbed reactive oxygen in alcohol activation on npAu catalysts. AB - The activation of molecular O2 as well as the reactivity of adsorbed oxygen species is of central importance in aerobic selective oxidation chemistry on Au based catalysts. Herein, we address the issue of O2 activation on unsupported nanoporous gold (npAu) catalysts by applying a transient pressure technique, a temporal analysis of products (TAP) reactor, to measure the saturation coverage of atomic oxygen, its collisional dissociation probability, the activation barrier for O2 dissociation, and the facility with which adsorbed O species activate methanol, the initial step in the catalytic cycle of esterification. The results from these experiments indicate that molecular O2 dissociation is associated with surface silver, that the density of reactive sites is quite low, that adsorbed oxygen atoms do not spill over from the sites of activation onto the surrounding surface, and that methanol reacts quite facilely with the adsorbed oxygen atoms. In addition, the O species from O2 dissociation exhibits reactivity for the selective oxidation of methanol but not for CO. The TAP experiments also revealed that the surface of the npAu catalyst is saturated with adsorbed O under steady state reaction conditions, at least for the pulse reaction. PMID- 27376885 TI - Formamides as Lewis Base Catalysts in SN Reactions-Efficient Transformation of Alcohols into Chlorides, Amines, and Ethers. AB - A simple formamide catalyst facilitates the efficient transformation of alcohols into alkyl chlorides with benzoyl chloride as the sole reagent. These nucleophilic substitutions proceed through iminium-activated alcohols as intermediates. The novel method, which can be even performed under solvent-free conditions, is distinguished by an excellent functional group tolerance, scalability (>100 g) and waste-balance (E-factor down to 2). Chiral substrates are converted with excellent levels of stereochemical inversion (99 %->>=95 % ee). In a practical one-pot procedure, the primary formed chlorides can be further transformed into amines, azides, ethers, sulfides, and nitriles. The value of the method was demonstrated in straightforward syntheses of the drugs rac-Clopidogrel and S-Fendiline. PMID- 27376883 TI - Improved pulmonary function in the nitrofen model of congenital diaphragmatic hernia following prenatal maternal dexamethasone and/or sildenafil. AB - BACKGROUND: Pulmonary hypoplasia and hypertension is a leading cause of morbidity and mortality in congenital diaphragmatic hernia (CDH). The etiologic insult occurs early in gestation highlighting the potential of prenatal interventions. We evaluated prenatal pharmacologic therapies in the nitrofen CDH model. METHODS: Olive oil or nitrofen were administered alone or with dexamethasone (DM), sildenafil, or DM+sildenafil to pregnant rats. Newborn pups were assessed for lung function, structure and pulmonary artery (PA) flow and resistance. RESULTS: Prenatal DM treatment of CDH pups increased alveolar volume density (Vva), decreased interalveloar septal thickness, increased tidal volumes and improved ventilation without improving oxygenation or PA resistance. Sildenafil decreased PA resistance and improved oxygenation without improving ventilation or resulting in significant histologic changes. DM+sildenafil decreased PA resistance, improved oxygenation and ventilation while increasing Vva and decreasing interalveolar septal and pulmonary arteriole medial wall thickness. Lung and body weights were decreased in pups treated with DM and/or sildenafil. CONCLUSION: Prenatal DM or sildenafil treatment increased pulmonary compliance and decreased pulmonary vascular resistance respectively, and was associated with improved neonatal gas exchange but had a detrimental effect on lung and fetal growth. This study highlights the potential of individual and combined prenatal pharmacologic therapies for CDH management. PMID- 27376886 TI - Don't forget the dentist: Dental care use and needs of women with breast cancer. AB - PURPOSE: Patients with breast cancer may develop dental problems due to treatment. We examined the prevalence of their dental care use and needs, compared the prevalence of use with that of the general population, and examined which factors predict patients' dental care use. METHODS: Patients with primary breast cancer completed a questionnaire at 6 and 15 months post-diagnosis. Medical data were retrieved from medical records. The prevalence of dental care use and needs was examined with descriptive analyses. Associations between predictors and dental care use were examined with multivariate analyses. RESULTS: Twenty-one percent of 746 participants visited their dentist at least once in the past three months at 6 months, and 23% at 15 months post-diagnosis. The estimated percentage of women with at least one contact with their dentist in 12 months was low compared to the general female population (31.9% versus 79.5%). One to two percent of the respondents wanted more contact. Having dental care insurance (odds ratio 1.80; 95% CI, 1.08-3.00), chemotherapy (odds ratio 1.93; 95% CI, 1.21 3.06), and clinical distress 6 months post-diagnosis (odds ratio 2.53; 95% CI, 1.70-3.79) predicted use of dental care 9 months later. CONCLUSIONS: Up to 15 months post-diagnosis, breast cancer patients' dental care use is lower than warranted. Oncologists and cancer nurses are recommended to inform patients about dental risks, and to encourage them - particularly those without insurance - to visit their dentist. Occurrence of dental problems should be monitored, especially in patients who receive chemotherapy or who are clinically distressed. PMID- 27376887 TI - Efficacy of localization of non-palpable, invasive breast cancer: Wire localization vs. Iodine-125 seed: A historical comparison. AB - BACKGROUND: To achieve radical tumour excision in non-palpable breast cancer accurate tumour localization is essential. Historically, this has been achieved by wire localization (WL). Recently, new techniques like Iodine-125 seeds (IL) have become available. The aim of this study was to determine whether the results in case of IL are better than when WL is used. METHOD: A consecutive series of patients operated on because of non-palpable breast cancer was analysed. Between January 2007 and April 2011 WL was method of choice. From April 2011 till January 2013 IL was introduced and became the standard procedure. PRIMARY OUTCOMES WERE: success rate of (peri-) operative localization and radicality of the excision. Secondary outcomes were duration of operation and volumes of the excised tissue specimen. RESULTS: A total of 236 women were included; 149 women underwent WL and 87 women IL. The overall success rate for WL was 93.3%. In 10 patients (6.7%) WL failed because of peri-operative dislocation of the wire compared to only one failure to locate the seed in de postoperative specimen in the IL-group (1.1%, p = 0.098). Radical resection was obtained in 126/149 (84.6%) of the WL-patients, in comparison with 81/87 (93.1%) in the IL-group (p = 0.054). Median operation time and volume of the specimen was not significantly different between both groups. CONCLUSION: Localization of non-palpable breast cancer using Iodine-125 seeds is, at least, as good as the standard wire localization procedure. PMID- 27376888 TI - Mixed valent metals. AB - We review the theory of mixed-valent metals and make comparison with experiments. A single-impurity description of the mixed-valent state is discussed alongside the description of the nearly-integer valent or Kondo limit. The degeneracy N of the f-shell plays an important role in the description of the low-temperature Fermi-liquid state. In particular, for large N, there is a rapid cross-over between the mixed-valent and the Kondo limit when the number of f electrons is changed. We discuss the limitations on the application of the single-impurity description to concentrated compounds such as those caused by the saturation of the Kondo effect and those due to the presence of magnetic interactions between the impurities. This discussion is followed by a description of a periodic lattice of mixed-valent ions, including the role of the degeneracy N. The article concludes with a comparison of theory and experiment. Topics covered include the single-impurity Anderson model, Luttinger's theorem, the Friedel sum rule, the Schrieffer-Wolff transformation, the single-impurity Kondo model, Kondo screening, the Wilson ratio, local Fermi-liquids, Fermi-liquid sum rules, the Nozieres exhaustion principle, Doniach's diagram, the Anderson lattice model, the Slave-Boson method, etc. PMID- 27376889 TI - Enhanced binding of necrosis-targeting immunocytokine NHS-IL12 after local tumour irradiation in murine xenograft models. AB - PURPOSE: NHS-IL12 is an immunocytokine targeting necrotic tumour areas. IL12 shows anti-tumour activity. As local irradiation might induce additional necrosis in solid tumours, we aimed to evaluate the increase in intratumoural accumulation of NHS-IL12 after irradiation and correlate the findings with diffusion-weighted MRI studies in two xenograft models. METHODS: Human rhabdomyosarcoma (A204) and prostate cancer (PC3) cells were studied in vitro and as subcutaneous xenografts. Radiation sensitivity of the cell lines was assessed in vitro by colony formation assays. In vivo tumour necrosis was assessed based on apparent diffusion coefficients (ADC). Biodistribution of NHS-IL12 was evaluated with and without tumour irradiation using in vivo small-animal PET and ex vivo biodistribution. RESULTS: A204 and PC3 differed in their intrinsic radiation sensitivity. Accordingly, radiation-induced tumour necrosis was found only in A204 xenografts. In comparison with control, ADC was significantly increased after irradiation of A204 tumours with 1 * 8.0 Gy and 5 * 2.0 Gy, whereas no change in ADC was observed in PC3 xenografts in all irradiation regimes. ADC correlated with histology. An enhanced uptake of radiolabelled NHS-IL12 in A204 tumours was detected by PET and ex vivo biodistribution after tumour irradiation. In PC3 tumours, no increase in NHS-IL12 uptake was observed. CONCLUSIONS: In dependence of the tumour model, tumour irradiation enhanced tumour necrosis measured in MRI and histology. In vivo PET and ex vivo biodistribution showed enhanced binding of NHS-IL12 in rhabdomyosarcoma xenografts. Thus, enhanced binding of necrosis targeting immunocytokines might be a novel mechanism of additive effects in combination with irradiation. PMID- 27376890 TI - Red flags presented in current low back pain guidelines: a review. AB - OBJECTIVE: The purpose of this study was to identify and descriptively compare the red flags endorsed in guidelines for the detection of serious pathology in patients presenting with low back pain to primary care. METHOD: We searched databases, the World Wide Web and contacted experts aiming to find the multidisciplinary clinical guideline in low back pain in primary care, and selected the most recent one per country. We extracted data on the number and type of red flags for identifying patients with higher likelihood of serious pathology. Furthermore, we extracted data on whether or not accuracy data (sensitivity/specificity, predictive values, etc.) were presented to support the endorsement of specific red flags. RESULTS: We found 21 discrete guidelines all published between 2000 and 2015. One guideline could not be retrieved and after selecting one guideline per country we included 16 guidelines in our analysis from 15 different countries and one for Europe as a whole. All guidelines focused on the management of patients with low back pain in a primary care or multidisciplinary care setting. Five guidelines presented red flags in general, i.e., not related to any specific disease. Overall, we found 46 discrete red flags related to the four main categories of serious pathology: malignancy, fracture, cauda equina syndrome and infection. The majority of guidelines presented two red flags for fracture ('major or significant trauma' and 'use of steroids or immunosuppressors') and two for malignancy ('history of cancer' and 'unintentional weight loss'). Most often pain at night or at rest was also considered as a red flag for various underlying pathologies. Eight guidelines based their choice of red flags on consensus or previous guidelines; five did not provide any reference to support the choice of red flags, three guidelines presented a reference in general, and data on diagnostic accuracy was rarely provided. CONCLUSION: A wide variety of red flags was presented in guidelines for low back pain, with a lack of consensus between guidelines for which red flags to endorse. Evidence for the accuracy of recommended red flags was lacking. PMID- 27376891 TI - A longitudinal study on urinary cadmium and renal tubular protein excretion of nickel-cadmium battery workers after cessation of cadmium exposure. AB - PURPOSE: This study aimed to predict the outcome of urinary cadmium (Cd) excretion and renal tubular function by analyzing their evolution through 10 years after Cd exposure ceased. METHODS: Forty-one female, non-smoking workers were recruited from the year 2004 to 2009 when being removed from a nickel cadmium battery factory, and they were asked to provide morning urine samples on three consecutive days at enrollment and in every follow-up year until 2014. Urinary Cd and renal tubular function biomarkers including urinary beta2 microglobulin (beta2-m) and retinol-binding protein (RBP) concentrations were determined with the graphite furnace atomic absorption spectrometry and the enzyme-linked immunosorbent assays, respectively. RESULTS: The medians of baseline Cd, beta2-m and RBP concentrations at enrollment were 6.19, 105.38 and 71.84 MUg/g creatinine, respectively. Urinary beta2-m and RBP concentrations were both related to Cd concentrations over the years (beta absolute-beta2-m = 9.16, P = 0.008 and beta absolute-RBP = 6.42, P < 0.001, respectively). Cd, beta2-m and RBP concentrations in the follow-up years were all associated with their baseline concentrations (beta absolute-Cd = 0.61, P < 0.001; beta absolute-beta2-m = 0.64, P < 0.001; and beta absolute-RBP = 0.60, P < 0.001, respectively), and showed a decreasing tendency with the number of elapsed years relative to their baseline concentrations (beta relative-Cd = -0.20, P = 0.010; beta relative-beta2-m = 17.19, P = 0.002; and beta relative-RBP = -10.66, P < 0.001, respectively). CONCLUSIONS: Urinary Cd might eventually decrease to the general population level, and Cd-related tubular function would improve under the baseline conditions of this cohort. PMID- 27376892 TI - Effort-reward imbalance, cortisol secretion, and inflammatory activity in police officers with 24-h work shifts. AB - PURPOSE: Accumulating evidence shows that effort-reward imbalance (ERI) at work can cause various health problems. However, few studies have investigated the biological pathways linking ERI and health outcomes, and their findings have been inconsistent. In this study, we investigated the associations between ERI, the hypothalamic-pituitary-adrenocortical axis, and inflammation in a sample of police officers. METHODS: One hundred forty-two male police officers that were engaged in a working system of 24-h shifts were followed up during the work shift as well as during the two subsequent work-free days. Throughout this period, the participants provided two saliva samples each day for the 3-day period, and we measured the concentrations of cortisol and C-reactive protein (CRP) in the saliva. The police officers also completed the Japanese short version of the Effort-Reward Imbalance Questionnaire. RESULTS: The results of linear mixed model analyses controlled for possible confounding variables indicated that higher effort scores (p = 0.031) as well as effort-reward ratio (p = 0.080) were associated with lower cortisol levels, and the effect of effort was strengthened in the younger police officers (p = 0.017). Furthermore, higher effort scores were associated with higher CRP levels in younger police officers (p = 0.037). CONCLUSIONS: Our results indicate that effort, a component of ERI, has physiological effects in younger police officers, which possibly contribute to the development of stress-related diseases. PMID- 27376893 TI - [Nutritional management in geriatric traumatology]. AB - The prevalence of malnutrition or the risk of malnourishment is high among orthogeriatric patients and a poor nutritional status is associated with a negative outcome. A comprehensive management of preoperative and postoperative nutritional and fluid intake in these patients can help to improve the situation. The management includes identification of patients affected, a thorough assessment of the nutritional status, work-up of possible underlying causes, documentation of nutritional and fluid intake and, most importantly, procedures to improve the preoperative and postoperative nutritional situation. This article gives an overview of the recently updated recommendations on nutritional management in orthogeriatric patients as published by the orthogeriatric working group of the German Geriatric Society. PMID- 27376894 TI - SYBR Green II Dye-Based Real-Time Assay for Measuring Inhibitor Activity Against HIV-1 Reverse Transcriptase. AB - There are arrays of in vitro assays to quantify the activity of HIV-1 reverse transcriptase (HIV-1 RT). These assays utilize either chemically customized/labelled nucleotides, or TaqMan probes, or radiolabeled nucleotides/primers. Although several real-time PCR assays exist commercially for measuring the RT activity, which are usually used for quantifying the viral titres, these assays are not optimized for measuring the inhibitory concentrations (IC50) of HIV-1 RT inhibitors. Moreover, a recently established inorganic pyrophosphate-coupled enzyme assay cannot be employed for studying nonphosphorylated nucleoside reverse transcriptase inhibitors (NRTIs). In the present study, we have developed a novel one-step assay with native nucleotide substrates and SYBR Green II dye to determine IC50 values of triphosphorylated NRTIs against HIV-1 RT. Using exact batches of wild-type and mutant RT, and triphosphorylated NRTIs, we showed that our method gave IC50 values for inhibitors similar to that of an earlier published colorimetric assay with BrdUTP substrate (CABS). Our assay should be suitable for high-throughput screening of antiretroviral drugs and could also be suitable for studying drug resistance profiles. Additionally, we also used our assay to study inhibition by AZT in its nonphosphorylated form by supplementing the reaction mixture with necessary kinases and ATP. PMID- 27376895 TI - Micro/Nano Multilayered Scaffolds of PLGA and Collagen by Alternately Electrospinning for Bone Tissue Engineering. AB - The dual extrusion electrospinning technique was used to fabricate multilayered 3D scaffolds by stacking microfibrous meshes of poly(lactic acid-co-glycolic acid) (PLGA) in alternate fashion to micro/nano mixed fibrous meshes of PLGA and collagen. To fabricate the multilayered scaffold, 35 wt% solution of PLGA in THF DMF binary solvent (3:1) and 5 wt% solution of collagen in hexafluoroisopropanol (HFIP) with and without hydroxyapatite nanorods (nHA) were used. The dual and individual electrospinning of PLGA and collagen were carried out at flow rates of 1.0 and 0.5 mL/h, respectively, at an applied voltage of 20 kV. The density of collagen fibers in multilayered scaffolds has controlled the adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. The homogeneous dispersion of glutamic acid-modified hydroxyapatite nanorods (nHA-GA) in collagen solution has improved the osteogenic properties of fabricated multilayered scaffolds. The fabricated multilayered scaffolds were characterized using FT-IR, X-ray photoelectron spectroscopy, and transmission electron microscopy (TEM). The scanning electron microscopy (FE-SEM) was used to evaluate the adhesion and spreads of MC3T3-E1 cells on multilayered scaffolds. The activity of MC3T3-E1 cells on the multilayered scaffolds was evaluated by applying MTT, alkaline phosphatase, Alizarin Red, von Kossa, and cytoskeleton F-actin assaying protocols. The micro/nano fibrous PLGA-Col-HA scaffolds were found to be highly bioactive in comparison to pristine microfibrous PLGA and micro/nano mixed fibrous PLGA and Col scaffolds. PMID- 27376896 TI - Cholinesterase inhibitors, donepezil and rivastigmine, attenuate spatial memory and cognitive flexibility impairment induced by acute ethanol in the Barnes maze task in rats. AB - Central cholinergic dysfunction contributes to acute spatial memory deficits produced by ethanol administration. Donepezil and rivastigmine elevate acetylcholine levels in the synaptic cleft through the inhibition of cholinesterases-enzymes involved in acetylcholine degradation. The aim of our study was to reveal whether donepezil (acetylcholinesterase inhibitor) and rivastigmine (also butyrylcholinesterase inhibitor) attenuate spatial memory impairment as induced by acute ethanol administration in the Barnes maze task (primary latency and number of errors in finding the escape box) in rats. Additionally, we compared the influence of these drugs on ethanol-disturbed memory. In the first experiment, the dose of ethanol (1.75 g/kg, i.p.) was selected that impaired spatial memory, but did not induce motor impairment. Next, we studied the influence of donepezil (1 and 3 mg/kg, i.p.), as well as rivastigmine (0.5 and 1 mg/kg, i.p.), given either before the probe trial or the reversal learning on ethanol-induced memory impairment. Our study demonstrated that these drugs, when given before the probe trial, were equally effective in attenuating ethanol-induced impairment in both test situations, whereas rivastigmine, at both doses (0.5 and 1 mg/kg, i.p.), and donepezil only at a higher dose (3 mg/kg, i.p.) given prior the reversal learning, attenuated the ethanol-induced impairment in cognitive flexibility. Thus, rivastigmine appears to exert more beneficial effect than donepezil in reversing ethanol-induced cognitive impairments-probably due to its wider spectrum of activity. In conclusion, the ethanol-induced spatial memory impairment may be attenuated by pharmacological manipulation of central cholinergic neurotransmission. PMID- 27376897 TI - Bone remodeling markers as lithogenic risk factors in patients with osteopenia osteoporosis. AB - PURPOSE: To analyze the presence of phosphocalcic metabolism disorders in patients with osteopenia-osteoporosis without nephrolithiasis with respect to a control group. METHODS: A cross-sectional study was conducted in patients with osteopenia-osteoporosis without nephrolithiasis (n = 67) in lumbar spine or femur and in a control group (n = 61) with no lithiasis or bone disorders. Blood bone markers, phosphocalcic metabolism, fasting urine, 24-h urine lithogenic risk factors, and densitometry were recorded in both groups. SPSS 20.0 was used for statistical analysis. RESULTS: In comparison with the controls, significantly higher blood calcium (9.27 +/- 0.36 vs. 9.57 +/- 0.38, p = 0.0001), intact parathormone (45.6 +/- 14.9 vs. 53.8 +/- 18.9, p = 0.008), and alkaline phosphatase (61.9 +/- 20.9 vs. 70.74 +/- 18.9, p = 0.014) levels were found in patients with osteopenia-osteoporosis. In the 24-h urine test, citrate (1010.7 +/ 647.8 vs. 617.6 +/- 315.8, p = 0.0001) and oxalate (28.21 +/- 17.65 vs. 22.11 +/ 16.49, p = 0.045) levels were significantly lower in osteopenia-osteoporosis patients than in controls, with no significant difference in calcium (187.3 +/- 106.9 vs. 207.06 +/- 98.12, p = 0.27) or uric acid (540.7 +/- 186.2 vs. 511.9 +/- 167.06, p = 0.35) levels. Patients with osteopenia-osteoporosis had significantly higher levels of lithogenic risk factors associated with bone remodeling, including significantly increased beta-crosslaps and osteocalcin values and higher beta-crosslaps/osteocalcin ratios. CONCLUSION: Patients with osteopenia osteoporosis without nephrolithiasis showed phosphocalcic metabolism disorders as well as lower urinary citrate and higher beta-crosslaps/osteocalcin and fasting calcium/creatinine ratios, which would increase the risk of nephrolithiasis. Hence, prospective studies are warranted to evaluate the long-term risks. PMID- 27376898 TI - Treatment strategies for upper tract urothelial carcinoma (UTUC) of a solitary kidney: a single-institutional analysis of 61 cases. AB - OBJECTIVE: To explore the treatment strategies for patients with upper tract urothelial carcinoma (UTUC) of a solitary kidney. METHODS: A retrospective analysis of 61 cases who underwent operation for UTUC of a solitary kidney from 2000 to 2012 was performed. Radical nephroureterectomy (RNU) or conservative management was performed. Patients were divided into three groups according to preoperative renal function: group A (eGFR >= 60 mL/min), group B (15 mL/min <= eGFR < 60 mL/min) and group C (eGFR < 15 mL/min). We analyzed treatment outcomes of patients with different renal function and surgical approaches. RESULTS: No significant complications were observed, and short-time recovery after operation was satisfactory in all patients. The 5-year cancer-specific survival (CSS) rates for the groups A, B and C were 92.9, 75.3 and 63.7 %, respectively (p = 0.683). The 5-year overall survival (OS) and recurrence-free survival rates were 92.9 and 53 % for group A, respectively, 75.3 and 64.8 % for group B, respectively, and 63.7 and 29.5 % for group C, respectively (all p > 0.1). The conservative management arm was associated with older age (p = 0.002), smaller tumor size (p = 0.013), lack of renal replacement history (p = 0.007) and better preoperative renal function (p = 0.002). There were no significant differences in 5-year CSS, OS or recurrence-free survival between the RNU and conservative management groups. Long-term hemodialysis was required in only three patients in the conservative management arm. CONCLUSION: Long-term oncological outcomes after conservative management are comparable to RNU in selected cases, and conservative management should be considered an alternative treatment measure. Preoperative renal function and clinicopathological characteristics are important in surgery selection for patients with UTUC of a solitary kidney. PMID- 27376899 TI - Status of dosage compensation of X chromosome in bovine genome. AB - Dosage compensation system with X chromosome upregulation and inactivation have evolved to overcome the genetic imbalance between sex chromosomes in both male and female of mammals. Although recent development of chromosome-wide technologies has allowed us to test X upregulation, discrete data processing and analysis methods draw disparate conclusions. A series of expression studies revealed status of dosage compensation in some species belonging to monotremes, marsupials, rodents and primates. However, X upregulation in the Artiodactyla order including cattle have not been studied yet. In this study, we surveyed the genome-wide transcriptional upregulation in X chromosome in cattle RNA-seq data using different gene filtration methods. Overall examination of RNA-seq data revealed that X chromosome in the pituitary gland expressed more genes than in other peripheral tissues, which was consistent with the previous results observed in human and mouse. When analyzed with globally expressed genes, a median X:A expression ratio was 0.94. The ratio of 1-to-1 ortholog genes between chicken and mammals, however, showed considerable reduction to 0.68. These results indicate that status of dosage compensation for cattle is not deviated from those found in rodents and primate, and this is consistent with the evolutionary history of cattle. PMID- 27376901 TI - Care Bundles for Acute Kidney Injury: Do They Work? AB - Acute kidney injury (AKI) is common and is associated with poor patient outcomes, which in some cases appear associated with deficiencies in the provision of care. Care bundles (CBs) are a structured set of practices designed to improve the processes of care delivery and ultimately patient outcomes, and there have been some demonstrations of their utility in areas such as ventilator-associated pneumonia and in sepsis management. While there is a strong rationale for their use, the evidence base around AKI CBs is small but growing. Here, we review the existing data on the effectiveness of AKI CB and discuss optimal approaches to their future study. (c) 2016 S. Karger AG, Basel. PMID- 27376900 TI - Relationship of Stigma and Depression Among Newly HIV-Diagnosed Chinese Men Who Have Sex with Men. AB - Little is known about the relationship between HIV stigma and depression among newly diagnosed HIV-infected men who have sex with men (MSM). We measured HIV related stigma and current depression using standard scales among 367 Chinese MSM who had been diagnosed very recently with HIV infection, analyzing key associations with multivariable ordinal logistic regression. Current depression prevalence was 36 %. Median scores for felt, vicarious, and internalized stigma were 17, 2, and 5, respectively, each on a 0-30 scale. A one-point increase in the total stigma score was associated with a 4 % increase in the odds of current depression [adjusted odds ratio (aOR) = 1.04, 95 % confidence interval (CI) 1.03 1.05]. Internalized stigma had the strongest association with depression (aOR = 1.09, 95 % CI 1.07-1.12). Effective interventions to address coping with HIV related stigma immediately following HIV-diagnosis might help reduce depression, improve long-term mental health, and improve engagement in their care. PMID- 27376902 TI - Chemoselective Synthesis of Carbamates using CO2 as Carbon Source. AB - Synthesis of carbamates directly from amines using CO2 as the carbon source is a straightforward and sustainable approach. Herein, we describe a highly effective and chemoselective methodology for the synthesis of carbamates at room temperature and atmospheric pressure. This methodology can also be applied to protect the amino group in amino acids and peptides, and also to synthesize important pharmaceuticals. PMID- 27376906 TI - Laryngotracheal reconstruction with a prefabricated fasciocutaneous free flap for recurrent papillary thyroid carcinoma. AB - BACKGROUND: Prefabricated composite free flaps have been described as a technique for reconstruction of laryngotracheal defects. METHODS: We present a 74-year-old woman with recurrent papillary thyroid carcinoma (PTC) who was initially treated with thyroidectomy, tracheal resection, and subsequent vocal cord medialization. The patient's recurrent disease was treated with partial laryngectomy and reconstruction using a prefabricated composite free flap. A 2-stage procedure was performed using conchal cartilage to create a prefabricated radial forearm free flap. RESULTS: The patient's airway was successfully reconstructed with preservation of speech and swallow function. CONCLUSION: This case provides further evidence supporting the use of prefabricated free flaps in airway reconstruction and the ability to obtain successful outcomes in a patient with multiple prior surgeries in the operative field and requiring adjuvant external beam radiation therapy. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2512 E2514, 2016. PMID- 27376907 TI - Prior Lubrication of the Urethra Does Not Reduce Pain Perception in Men Undergoing Flexible Cystoscopy. AB - OBJECTIVE: The study aimed to test the hypothesis that the instillation of lidocaine gel does not reduce the pain related to flexible cystoscopy. MATERIAL AND METHODS: A prospective randomized study was designed to compare the pain perception between intraurethral instillation of lidocaine gel and saline solution in flexible cystoscopy. One hundred consecutive male patients attending for flexible cystoscopy were randomized to receive 10 ml of lidocaine gel or 10 ml of saline solution. Saline solution was also used for the irrigation pressure. Patients recorded their pain on a 10 cm Visual Analog Scale before and after the procedure. Patients also assessed whether the cystoscopy was more painful than the previous one. Statistical comparison was made using the t test for parametrical data and the Mann-Whitney U test for non-parametrical data. RESULTS: Mean pain score in the lidocaine group was 0.67 +/- 1.11 cm (range 0-5) compared to 0.55 +/- 1.10 cm (range 0-5) in the saline solution group. Pain perception did not differ significantly between the 2 groups (mean difference 0.12 cm, 95% CI 0.32 to 0.55, p = 0.40). CONCLUSIONS: Prior lubrication of the urethra does not reduce the pain produced during flexible cystoscopy. The introduction of flexible cystoscopes under direct vision and with an irrigation pressure might guarantee sufficient comfort and the lubricant gel instillation could be avoided. PMID- 27376908 TI - Shock, but no shift: Hospitals' responses to changes in patient insurance mix. AB - Medicaid reimburses healthcare providers for services at a lower rate than any other type of insurance coverage. To account for the burden of treating Medicaid patients, providers claim that they must cost-shift by raising the rates of individuals covered by private insurance. Previous investigations of cost shifting has produced mixed results. In this paper, I exploit a disabled Medicaid expansion where crowd-out was complete to investigate cost-shifting. I find that hospitals reduce the charge rates of the privately insured. Given that Medicaid is expanding in several states under the Affordable Care Act, these results may alleviate cost-shifting concerns of the reform. PMID- 27376909 TI - Quantile treatment effects of job loss on health. AB - Studies on health effects of job loss mostly estimate mean effects. We argue that the effects might differ over the distribution of the health status and use quantile regression methods to provide a more complete picture. To take the potential endogeneity of job loss into account, we estimate quantile treatment effects where we rely on job loss due to plant closures. We find that the effect of job loss indeed varies across the mental and physical health distribution. Job loss due to plant closures affects physical health adversely for individuals in the middle and lower part of the health distribution while those in best physical condition do not seem to be affected. The results for mental health, though less distinct, point in the same direction. We find no effects on BMI. PMID- 27376910 TI - Reactive Multifunctional Template-Induced Preparation of Fe-N-Doped Mesoporous Carbon Microspheres Towards Highly Efficient Electrocatalysts for Oxygen Reduction. AB - A novel in situ replication and polymerization strategy is developed for the synthesis of Fe-N-doped mesoporous carbon microspheres (Fe-NMCSs). This material benefits from the synergy between the high catalytic activity of Fe-N-C and the fast mass transport of the mesoporous microsphere structure. Compared to commercial Pt/C catalysts, the Fe-NMCSs show a much better electrocatalytic performance in terms of higher catalytic activity, selectivity, and durability for the oxygen reduction reaction. PMID- 27376911 TI - Automated seizure detection systems and their effectiveness for each type of seizure. AB - Epilepsy affects almost 1% of the population and most of the approximately 20-30% of patients with refractory epilepsy have one or more seizures per month. Seizure detection devices allow an objective assessment of seizure frequency and a treatment tailored to the individual patient. A rapid recognition and treatment of seizures through closed-loop systems could potentially decrease morbidity and mortality in epilepsy. However, no single detection device can detect all seizure types. Therefore, the choice of a seizure detection device should consider the patient-specific seizure semiologies. This review of the literature evaluates seizure detection devices and their effectiveness for different seizure types. Our aim is to summarize current evidence, offer suggestions on how to select the most suitable seizure detection device for each patient and provide guidance to physicians, families and researchers when choosing or designing seizure detection devices. Further, this review will guide future prospective validation studies. PMID- 27376912 TI - A transactivation switchboard in wound healing. PMID- 27376913 TI - Sacral nerve stimulation lead implantation in partial sacral agenesis using intra operative computerized tomography. AB - AIM: Sacral nerve stimulation (SNS) lead implantation is a straightforward procedure for individuals with intact spinal vertebrae. When sacral anomalies are present, however, the anatomical and radiological reference points used for the accurate placement of the electrode may be absent or difficult to identify. METHOD: We describe an innovative surgical procedure of percutaneous nerve evaluation for SNS in a patient with faecal incontinence secondary to a congenital imperforate anus and partial sacral agenesis using a surgical imaging platform (O-arm system) under neurophysiological control. RESULTS: Using intra operative CT and neuronavigation, the insertion point at the skin was identified. The lead was introduced into the right-sided S3 foramen and placed at the correct depth. An appropriate motor response was obtained after stimulation and neurophysiological control confirmed that the right S3 root was being stimulated. CONCLUSION: Our experience showed that O-arm guided navigation can be used to overcome the difficulty of SNS lead placement in patients with partial sacral agenesis who have faecal incontinence. PMID- 27376914 TI - Modelling of marine radionuclide dispersion in IAEA MODARIA program: Lessons learnt from the Baltic Sea and Fukushima scenarios. AB - State-of-the art dispersion models were applied to simulate (137)Cs dispersion from Chernobyl nuclear power plant disaster fallout in the Baltic Sea and from Fukushima Daiichi nuclear plant releases in the Pacific Ocean after the 2011 tsunami. Models were of different nature, from box to full three-dimensional models, and included water/sediment interactions. Agreement between models was very good in the Baltic. In the case of Fukushima, results from models could be considered to be in acceptable agreement only after a model harmonization process consisting of using exactly the same forcing (water circulation and parameters) in all models. It was found that the dynamics of the considered system (magnitude and variability of currents) was essential in obtaining a good agreement between models. The difficulties in developing operative models for decision-making support in these dynamic environments were highlighted. Three stages which should be considered after an emergency, each of them requiring specific modelling approaches, have been defined. They are the emergency, the post-emergency and the long-term phases. PMID- 27376915 TI - Comparison of regional air dispersion simulation and ambient air monitoring data for the soil fumigant 1,3-dichloropropene. AB - SOFEA v2.0 is an air dispersion modeling tool used to predict acute and chronic pesticide concentrations in air for large air sheds resulting from agronomic practices. A 1,3-dichloropropene (1,3-D) air monitoring study in high use townships in Merced County, CA, logged 3-day average air concentrations at nine locations over a 14.5month period. SOFEA, using weather data measured at the site, and using a historical CDPR regulatory assumption of a constant 320m mixing height, predicted the general pattern and correct order of magnitude for 1,3-D air concentrations as a function of time, but failed to estimate the highest observed 1,3-D concentrations of the monitoring study. A time series and statistical comparison of the measured and modeled data indicated that the model underestimated 1,3-D concentrations during calm periods (wind speed <1m/s), such that the annual average concentration was under predicted by approximately 4.7 fold, and the variability was not representative of the measured data. Calm periods are associated with low mixing heights (MHs) and are more prevalent in the Central Valley of CA during the winter months, and thus the assumption of a constant 320m mixing height is not appropriate. An algorithm was developed to calculate the MH using the air temperature in the weather file when the wind speed was <1m/s. When the model was run using the revised MHs, the average of the modeled 1,3-D concentration Probability Distribution Function (PDF) was within 5% of the measured PDF, and the variability in modeled concentrations more closely matched the measured dataset. Use of the PCRAMMET processed weather data from the site (including PCRAMMET MH) resulted in the global annual average concentration within 2-fold of measured data. Receptor density was also found to have an effect on the modeled 1,3-D concentration PDF, and a 50*50 receptor grid in the nine township domain captured the measured 1,3-D concentration distribution much better than a 3*3 receptor grid (i.e., simulated receptors at the nine monitoring locations). Comparison of the monitored and simulated PDF for 72-h 1,3-D concentrations indicated that SOFEA slightly over predicts the 1,3-D concentration distribution at all percentiles below the 99th with slight under prediction of the 99-100th percentile values. This suggests that without further refinement, the SOFEA2 model, based upon field validation observations, will result in representative but conservative estimates of lifetime exposure to 1,3-D for bystanders in 1,3-D use areas. PMID- 27376916 TI - A sustainable on-line CapLC method for quantifying antifouling agents like irgarol-1051 and diuron in water samples: Estimation of the carbon footprint. AB - In this work, in-tube solid phase microextraction (in-tube SPME) coupled to capillary LC (CapLC) with diode array detection has been reported, for on-line extraction and enrichment of booster biocides (irgarol-1051 and diuron) included in Water Frame Directive 2013/39/UE (WFD). The analytical performance has been successfully demonstrated. Furthermore, in the present work, the environmental friendliness of the procedure has been quantified by means of the implementation of the carbon footprint calculation of the analytical procedure and the comparison with other methodologies previously reported. Under the optimum conditions, the method presents good linearity over the range assayed, 0.05 10MUg/L for irgarol-1051 and 0.7-10MUg/L for diuron. The LODs were 0.015MUg/L and 0.2MUg/L for irgarol-1051 and diuron, respectively. Precision was also satisfactory (relative standard deviation, RSD<3.5%). The proposed methodology was applied to monitor water samples, taking into account the EQS standards for these compounds. The carbon footprint values for the proposed procedure consolidate the operational efficiency (analytical and environmental performance) of in-tube SPME-CapLC-DAD, in general, and in particular for determining irgarol 1051 and diuron in water samples. PMID- 27376917 TI - Chemical profiles of urban fugitive dust PM2.5 samples in Northern Chinese cities. AB - Urban fugitive dust PM2.5 samples were collected in 11 selected cities in North China, and 9 ions (SO4(2-), NO3(-), Cl(-), F(-), Na(+), NH4(+), K(+), Mg(2+), and Ca(2+)) and 22 elements (Si, Al, S, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Br, Rb, Sr, Sn, Sb, Ba, and Pb) were determined to investigate chemical profiles of PM2.5. The coefficient of divergence (CD) was used to compare the similarities of the chemical profiles for fugitive dust among three regions in North China, and the results showed that their composition are quite similar. Total water soluble ions occupied 9.3% and 10.0% on average of road dust and construction dust, respectively, indicating that most of the materials in urban fugitive dust samples were insoluble. Ca(2+) was the most abundant cation and SO4(2-) dominated in anions. Soil dust loading was calculated to occupy 70.8% and 83.6% in road dust and construction dust, respectively. Ca, Si, Fe, and Al were the most abundant elements in all the samples, and Ca was absolutely the most abundant specie among the 22 detected elements in construction dust samples. Chemical species ratios were used to highlight the characteristics of urban fugitive dust by comparing with other types of aerosols. High Ca/Al ratio was a good marker to distinguish urban fugitive dust from Asian dust and Chinese loess. In addition, low K(+)/K and NO3(-)/SO4(2-), and high Zn/Al and Pb/Al ratios were good indicators to separate urban fugitive dust from desert dust, Chinese loess, or urban PM2.5 samples. PMID- 27376918 TI - Heat-related mortality in Cyprus for current and future climate scenarios. AB - Extreme temperatures have long been associated with adverse health impacts, ranging from minor illness, to increased hospitalizations and mortality. Heat related mortality during summer months is likely to become an increasing public health problem in future due to the effects of climate change. We performed a health impact assessment for heat-related mortality for the warm months of April September for the years 2004 to 2009 inclusive, for the city of Nicosia and for Cyprus as a whole, based on separately derived exposure-response functions. We further estimated the potential future heat-related mortality by including climate projections for southern Europe, which suggest changes in temperature of between 1 degrees C and 5 degrees C over the next century. There were 32 heat related deaths per year in Cyprus over the study period. When adding the projected increase in temperature due to climate change, there was a substantial increase in mortality: for a 1 degrees C increase in temperature, heat related mortality in Cyprus was estimated to double to 64 per year, and for a 5 degrees C increase, heat-related mortality was expected to be 8 times the baseline rate for the warm season (281 compared with 32). This analysis highlights the importance of preparing for potential health impacts due to heat in Cyprus, particularly under a changing climate. PMID- 27376919 TI - An integrated numerical framework for water quality modelling in cold-region rivers: A case of the lower Athabasca River. AB - There is a great deal of interest to determine the state and variations of water quality parameters in the lower Athabasca River (LAR) ecosystem, northern Alberta, Canada, due to industrial developments in the region. As a cold region river, the annual cycle of ice cover formation and breakup play a key role in water quality transformation and transportation processes. An integrated deterministic numerical modelling framework is developed and applied for long term and detailed simulation of the state and variation (spatial and temporal) of major water quality constituents both in open-water and ice covered conditions in the lower Athabasca River (LAR). The framework is based on the a 1D and a 2D hydrodynamic and water quality models externally coupled with the 1D river ice process models to account for the cold season effects. The models are calibrated/validated using available measured data and applied for simulation of dissolved oxygen (DO) and nutrients (i.e., nitrogen and phosphorus). The results show the effect of winter ice cover on reducing the DO concentration, and a fluctuating temporal trend for DO and nutrients during summer periods with substantial differences in concentration between the main channel and flood plains. This numerical frame work can be the basis for future water quality scenario-based studies in the LAR. PMID- 27376921 TI - Assessment of the impact of sea-level rise due to climate change on coastal groundwater discharge. AB - An assessment of sea intrusion into coastal aquifers as a consequence of local sea-level rise (LSLR) due to climate change was carried out at Murgia and Salento in southern Italy. The interpolation of sea-level measurements at three tide gauge stations was performed during the period of 2000 to 2014. The best fit of measurements shows an increasing rate of LSLR ranging from 4.4mm/y to 8.8mm/y, which will result in a maximum LSLR of approximately 2m during the 22nd century. The local rate of sea-level rise matches recent 21st and 22nd century projections of mean global sea-level rise determined by other researchers, which include increased melting rates of the Greenland and Antarctic ice sheets, the effect of ocean thermal expansion, the melting of glaciers and ice caps, and changes in the quantity of stored land water. Subsequently, Ghyben-Herzberg's equation for the freshwater/saltwater interface was rewritten in order to determine the decrease in groundwater discharge due to the maximum LSLR. Groundwater flow simulations and ArcGIS elaborations of digital elevation models of the coast provided input data for the Ghyben-Herzberg calculation under the assumption of head-controlled systems. The progression of seawater intrusion due to LSLR suggests an impressive depletion of available groundwater discharge during the 22nd century, perhaps as much as 16.1% of current groundwater pumping for potable water in Salento. PMID- 27376920 TI - Real-time monitoring of nutrients and dissolved organic matter in rivers: Capturing event dynamics, technological opportunities and future directions. AB - Excessive riverine nutrient concentrations threaten aquatic ecosystem structure and functioning and can pose substantial risks to human health. Robust monitoring strategies are therefore required to generate reliable estimates of river nutrient loads and to improve understanding of the catchment processes that drive nutrient fluxes. Furthermore, these data are vital for prediction of future trends under changing environmental conditions and thus the development of appropriate mitigation measures. In recent years, technological developments have led to an increase in the use of in-situ nutrient analysers, which enable measurements at far higher temporal resolutions than can be achieved with discrete sampling and subsequent laboratory analysis. In this paper, we review the principles underlying the key techniques used for in-situ nutrient monitoring and highlight both the advantages, opportunities and challenges associated with high-resolution sampling programs. We then suggest how adaptive monitoring strategies, comprising several different temporal sample frequencies, controlled by one or more 'trigger variables' (e.g. river stage, turbidity, or nutrient concentration), can advance our understanding of catchment nutrient dynamics while simultaneously overcoming many of the practical and economic challenges encountered in typical in-situ river nutrient monitoring applications. We present examples of short-term variability in river nutrient dynamics, driven by complex catchment behaviour, which support our case for the development of monitoring systems that can adapt in real-time to rapid changes in environmental conditions. Finally, we suggest future research directions based on emerging technologies in this field. PMID- 27376922 TI - Inhibition of multixenobiotic resistance transporters (MXR) by silver nanoparticles and ions in vitro and in Daphnia magna. AB - The P-glycoprotein (P-gp, ABCB1) and multidrug resistance associated protein 1 (MRP1), important members of the ABC (ATP-binding cassette) transporters, protect cells and organisms via efflux of xenobiotics and are responsible for the phenomenon of multidrug or multixenobiotic resistance (MXR). In this study we first evaluated, in vitro, the interaction of silver nanoparticles (Ag NPs, 20, 23 and 27nm), Ag 200nm particles and Ag ions (AgNO3) with MXR efflux transporters using MDCKII and the P-gp over-expressing MDCKII-MDR1 cells and calcein-AM as a substrate of the transporters. Next the in vivo modulation of MXR activity was studied in Daphnia magna juveniles with the model P-gp and MRP1 inhibitors verapamil-HCl and MK571, respectively. The common environmental contaminants perfluorooctane sulfonate and bisphenol A, previously observed to interfere with the P-gp in vitro, also inhibited the efflux of calcein in vivo. Small-sized Ag NPs (with biomolecules present on the surface) and AgNO3 inhibited the MXR activity in daphnids and MDCKII-MDR1 cells, but abcb1 gene expression remained unchanged. Both Ag NPs and dissolved ions contributed to the effects. This study provides evidence of the interference of Ag NPs and AgNO3 with the MXR activity both in vitro and in D. magna, and should be taken into account when Ag NP toxicity is assessed. PMID- 27376923 TI - Acidification of stratum corneum prevents the progression from atopic dermatitis to respiratory allergy. AB - The presence of congenitally impaired skin barrier followed by atopic dermatitis (AD) is an initial step in the atopic march. The maintenance of acidic pH in the stratum corneum (SC) has been suggested as a therapeutic or preventive strategy for barrier impairment caused by skin inflammation. To determine whether an AD murine model, flaky tail mice, with inherited filaggrin deficiency could develop airway inflammation by repeated topical application followed by nasal inhalation of house dust mite (HDM) antigen (defined as a novel "atopic march animal model"), and whether maintenance of an acidic SC environment by continuous application of acidic cream could interrupt the following atopic march. During the course of HDM treatment, acidic cream (pH2.8) or neutral cream (pH7.4) was applied to flaky tail mice twice daily. Repeated applications and inhalations of HDM to flaky tail mice induced AD skin lesions followed by respiratory allergies. Maintenance of SC acidity inhibited the occurrence of respiratory allergic inflammation as well as AD-like skin lesions. Collectively, a novel atopic march model could be developed by repeated epicutaneous and nasal applications of HDM to flaky tail mice, and that the acidification of SC could prevent the atopic march from AD to respiratory allergy. PMID- 27376924 TI - Development of SNARC and distance effects and their relation to mathematical and visuospatial abilities. AB - The current experiment measured symbolic SNARC (Spatial-Numeric Association of Response Codes) and distance effects in school-aged children and investigated the relation between these measures and visuospatial skills and mathematics ability. In the experiment, 6-, 7-, and 8-year-olds performed a magnitude-relevant SNARC task, in which they indicated whether a target number was less or greater than 5, as well as standardized tests of visuospatial skills (Developmental Test of Visual Perception-Second Edition, DTVP-2) and mathematics ability (Test of Early Mathematics Ability-Third Edition, TEMA-3). Consistent with previous research using numerical SNARC tasks with Western children, all age groups exhibited robust distance effects, and SNARC effects were observed only in 7- and 8-year olds. Distance effects, but not SNARC effects, were moderately but significantly correlated with a subtest of the DTVP-2 measuring the ability to mentally manipulate objects in space but no other subtest. These data suggest that mental orientation abilities, but perhaps not visuospatial skills involved in visual perception and visuomotor coordination, are related to some aspects of mental number line development. Nevertheless, no relation was observed between SNARC or distance effects and mathematics ability. This result is consistent with previous developmental studies investigating the association between SNARC and math skill. However, these data are inconsistent with most experiments assessing the relationship between distance effect strength and math-a difference that can likely be attributed to the fact that a magnitude-relevant SNARC task was employed as opposed to a traditional SNARC parity task. PMID- 27376925 TI - Children's experiences of dental anxiety. AB - BACKGROUND: Dental anxiety is common among children. Although there is a wealth of research investigating childhood dental anxiety, little consideration has been given to the child's perspective. AIM: This qualitative study sought to explore with children their own experiences of dental anxiety using a cognitive behavioural therapy assessment model. DESIGN: Face-to-face, semi-structured interviews were conducted with dentally anxious children aged 11-16 years. The Five Areas model was used to inform the topic guide and analysis. Data were analysed using a framework approach. RESULTS: In total, 13 children were interviewed. Participants described their experiences of dental anxiety across multiple dimensions (situational factors and altered thoughts, feelings, physical symptoms, and behaviours). Participants placed considerable value on communication by dental professionals, with poor communication having a negative influence on dental anxiety and the dentist-patient relationship. CONCLUSIONS: This study confirms the Five Areas model as an applicable theoretical model for the assessment of childhood dental anxiety. Children provided insights about their own dental anxiety experiences that have not previously been described. PMID- 27376926 TI - Racial disparities in primary prevention of incontinence among older adults at nursing home admission. AB - AIMS: Maintaining continence of nursing home (NH) residents promotes dignity and well-being and may reduce morbidity and healthcare treatment costs. To determine the prevalence of older continent adults who received primary prevention of incontinence at NH admission, assess whether there were racial or ethnic disparities in incontinence prevention, and describe factors associated with any disparities. METHODS: The design was an observational cross-sectional study of a nation-wide cohort of older adults free of incontinence at NH admission (n = 42,693). Four US datasets describing NH and NH resident characteristics, practitioner orders for NH treatment/care, and socioeconomic and sociodemographic status of the community surrounding the NHs were analyzed. Disparities were analyzed for four minority groups identified on the minimum data set using the Peters-Belson method and covariates at multiple levels. RESULTS: Twelve percent of NH admissions received incontinence prevention. There was a significant disparity (2%) in incontinence prevention for Blacks (P < 0.05): Fewer Black admissions (8.6%) were observed to receive incontinence prevention than was expected had they been part of the White group (10.6%). The percentage of White admissions receiving incontinence prevention was 10.6%. Significant factors associated with disparity in receiving incontinence prevention were having greater deficits in ADL function and cognition and more comorbidities. No disparity disadvantaging the other minority groups was found. CONCLUSIONS: Greater efforts for instituting incontinence prevention at the time of NH admission are needed. Eliminating racial disparities in incontinence prevention seems an attainable goal. Appropriate staff training, organizational commitment, and monitoring progress toward equitable outcomes can help achieve this goal. Neurourol. Urodynam. 36:1124-1130, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27376927 TI - Understanding mechanism of sea cucumber Apostichopus japonicus aestivation: Insights from TMT-based proteomic study. AB - Marine invertebrate aestivation is a unique strategy for summer survival in response to hot marine conditions. The sea cucumber, Apostichopus japonicus, is an excellent model marine invertebrate for studies of environmentally-induced aestivation. In the present study, we used a tandem mass tag (TMT)-coupled LC MS/MS approach to identify and quantify the global proteome expression profile over the aestivation-arousal cycle of A. japonicus. A total of 3920 proteins were identified from the intestine of sea cucumber. Among them, 630 proteins showed significant differential expression when comparing three conditions of sea cucumbers: non-aestivating (active), deep-aestivation (at least 15days of continuous aestivation), and arousal after aestivation (renewed moving and feeding). Sea cucumbers in deep aestivation showed substantial differentially expressed proteins (143 up-regulated and 267 down-regulated proteins compared with non-aestivating controls). These differentially expressed proteins suggested that protein and phospholipid probably are major fuel sources during hypometabolism and a general attenuation of carbohydrate metabolism was observed during deep aestivation. Differentially expressed proteins also provided the first global picture of a shift in protein synthesis, protein folding, DNA binding, apoptosis, cellular transport and signaling, and cytoskeletal proteins during deep aestivation in sea cucumbers. A comparison of arousal from aestivation with deep aestivation, revealed a general reversal of the changes that occurred in aestivation for most proteins. Western blot detection further validated the significant up-regulation of HSP70 and down-regulation of methyltransferase-like protein 7A-like in deep-aestivation. Our results suggest that there is substantial post-transcriptional regulation of proteins during the aestivation-arousal cycle in sea cucumbers. PMID- 27376929 TI - Interactive and additive influences of Gender, BMI and Apolipoprotein 4 on cognition in children chronically exposed to high concentrations of PM2.5 and ozone. APOE 4 females are at highest risk in Mexico City. AB - Children's air pollution exposures are associated with systemic and brain inflammation and the early hallmarks of Alzheimer's disease (AD). The Apolipoprotein E (APOE) 4 allele is the most prevalent genetic risk for AD, with higher risk for women. We assessed whether gender, BMI, APOE and metabolic variables in healthy children with high exposures to ozone and fine particulate matter (PM2.5) influence cognition. The Wechsler Intelligence Scale for Children (WISC-R) was administered to 105 Mexico City children (12.32+/-5.4 years, 69 APOE 3/3 and 36 APOE 3/4). APOE 4v 3 children showed decrements on attention and short term memory subscales, and below-average scores in Verbal, Performance and Full Scale IQ. APOE 4 females had higher BMI and females with normal BMI between 75 94% percentiles had the highest deficits in Total IQ, Performance IQ, Digit Span, Picture Arrangement, Block Design and Object Assembly. Fasting glucose was significantly higher in APOE 4 children p=0.006, while Gender was the main variable accounting for the difference in insulin, HOMA-IR and leptin (p<.05). Gender, BMI and APOE influence children's cognitive responses to air pollution and glucose is likely a key player. APOE 4 heterozygous females with >75% to <94% BMI percentiles are at the highest risk of severe cognitive deficits (1.5-2SD from average IQ). Young female results highlight the urgent need for gender targeted health programmes to improve cognitive responses. Multidisciplinary intervention strategies could provide paths for prevention or amelioration of female air pollution targeted cognitive deficits and possible long-term AD progression. PMID- 27376928 TI - Leiodermatolide, a novel marine natural product, has potent cytotoxic and antimitotic activity against cancer cells, appears to affect microtubule dynamics, and exhibits antitumor activity. AB - Pancreatic cancer, the fourth leading cause of cancer death in the United States, has a negative prognosis because metastasis occurs before symptoms manifest. Leiodermatolide, a polyketide macrolide with antimitotic activity isolated from a deep water sponge of the genus Leiodermatium, exhibits potent and selective cytotoxicity toward the pancreatic cancer cell lines AsPC-1, PANC-1, BxPC-3, and MIA PaCa-2, and potent cytotoxicity against skin, breast and colon cancer cell lines. Induction of apoptosis by leiodermatolide was confirmed in the AsPC-1, BxPC-3 and MIA PaCa-2 cells. Leiodermatolide induces cell cycle arrest but has no effects on in vitro polymerization or depolymerization of tubulin alone, while it enhances polymerization of tubulin containing microtubule associated proteins (MAPs). Observations through confocal microscopy show that leiodermatolide, at low concentrations, causes minimal effects on polymerization or depolymerization of the microtubule network in interphase cells, but disruption of spindle formation in mitotic cells. At higher concentrations, depolymerization of the microtubule network is observed. Visualization of the growing microtubule in HeLa cells expressing GFP-tagged plus end binding protein EB-1 showed that leiodermatolide stopped the polymerization of tubulin. These results suggest that leiodermatolide may affect tubulin dynamics without directly interacting with tubulin and hint at a unique mechanism of action. In a mouse model of metastatic pancreatic cancer, leiodermatolide exhibited significant tumor reduction when compared to gemcitabine and controls. The antitumor activities of leiodermatolide, as well as the proven utility of antimitotic compounds against cancer, make leiodermatolide an interesting compound with potential chemotherapeutic effects that may merit further research. PMID- 27376930 TI - Association of cold temperature and mortality and effect modification in the subtropical plateau monsoon climate of Yuxi, China. AB - BACKGROUND: Consistent evidence has shown excess mortality associated with cold temperature, but some important details of the cold-mortality association (e.g. slope and threshold) have not been adequately investigated and few studies focused on the cold effect in high-altitude areas of developing countries. We attempted to quantify the cold effect on mortality, identify the details, and evaluate effect modification in the distinct subtropical plateau monsoon climate of Yuxi, a high plateau region in southwest China. METHODS: From daily mortality and meteorological data during 2009-2014, we used a quasi-Poisson model combined with a "natural cubic spline-natural cubic spline" distributed lag non-linear model to estimate the temperature-mortality relationship and then a simpler "hockey-stick" model to investigate the cold effect and details. RESULTS: Cold temperature was associated with increased mortality, and the relative risk of cold effect (1st relative to 10th temperature percentile) on non-accidental, cardiovascular, and respiratory mortality for lag 0-21 days was 1.40 (95% confidence interval: 1.19-1.66), 1.61 (1.28-2.02), and 1.13 (0.78-1.64), respectively. A 1 degrees C decrease below a cold threshold of 9.1 degrees C (8th percentile) for lags 0-21 was associated with a 7.35% (3.75-11.09%) increase in non-accidental mortality. The cold-mortality association was not significantly affected by cause-specific mortality, gender, age, marital status, ethnicity, occupation, or previous history of hypertension. CONCLUSIONS: There is an adverse impact of cold on mortality in Yuxi, China, and a temperature of 9.1 degrees C is an important cut-off for cold-related mortality for residents. PMID- 27376931 TI - Waterscape determinants of net mercury methylation in a tropical wetland. AB - The periphyton associated with freshwater macrophyte roots is the main site of Hg methylation in different wetland environments in the world. The aim of this study was to test the use of connectivity metrics of water bodies, in the context of patches, in a tropical waterscape wetland (Guapore River, Amazonia, Brazil) as a predictor of potential net methylmercury (MeHg) production by periphyton communities. We sampled 15 lakes with different patterns of lateral connectivity with the main river channel, performing net mercury methylation potential tests in incubations with local water and Eichhornia crassipes root-periphyton samples, using (203)HgCl2 as a tracer. Physico-chemical variables, landscape data (morphological characteristics, land use, and lateral connection type of water bodies) using GIS resources and field data were analyzed with Generalized Additive Models (GAM). The net Me(203)Hg production (as % of total added (203)Hg) was expressive (6.2-25.6%) showing that periphyton is an important matrix in MeHg production. The model that best explained the variation in the net Me(203)Hg production (76%) was built by the variables: connection type, total phosphorus and dissolved organic carbon (DOC) in water (AICc=48.324, p=0.001). Connection type factor was the best factor to model fit (r(2)=0.32; p=0.008) and temporarily connected lakes had higher rates of net mercury methylation. Both DOC and total phosphorus showed positive significant covariation with the net methylation rates (r(2)=0.26; p=0.008 and r(2)=0.21; p=0.012 respectively). Our study suggests a strong relationship between rates of net MeHg production in this tropical area and the type of water body and its hydrological connectivity within the waterscape. PMID- 27376932 TI - Tool use disorders in neurodegenerative diseases: Roles of semantic memory and technical reasoning. AB - In the field of apraxia, it has been suggested that the ability to use tools and objects in daily life depends not only on semantic knowledge about tool function and context of use but also on technical reasoning about mechanical properties of tools and objects. The aim of the present work was to assess tool use abilities regarding these hypotheses in patients with neurodegenerative diseases and reduced autonomy. Performance of patients with Alzheimer's disease (AD) (n = 31), semantic dementia (SD) (n = 16) and corticobasal syndrome (CBS) (n = 7) was compared to that of healthy control participants (n = 31) in familiar tool use tasks, functional/contextual associations and mechanical problem solving (MPS). A conversion method was applied to data in order to avoid ceiling effects. Tool use disorders were found in all patient groups but the underlying reasons were different. Patients with SD had difficulties in imagining and selecting familiar tools due to the semantic loss but they performed in normal range in MPS tasks. Interestingly, they performed better with only one tool and its corresponding object, which is interpreted as a partial compensation of semantic loss by spared technical reasoning. Patients with CBS exhibited the reverse pattern, that is, MPS deficits without semantic loss. However, additional qualitative research is needed to disentangle the relative contributions of motor and technical reasoning deficits to this pattern. Both of these profiles were found in patients with AD. For all that, these patients did not commit the same errors as stroke patients with left brain-damage documented in previous works. Several hypotheses are proposed to account for the specificity of tool use disorders in neurodegenerative diseases, and recommendations are provided to caregivers. PMID- 27376933 TI - Meta-analytical and electrophysiological evidence for executive dysfunction in primary dystonia. AB - Impaired motor control in primary dystonia has been linked to cortico-basal ganglia alterations that may also give rise to changes in executive functioning. However, no conclusive evidence for executive dysfunction in patients with primary dystonia has been reported yet. We conducted a meta-analysis of the relationship between primary dystonia and performance on the Wisconsin Card Sorting Test (WCST), an established test of executive functioning. Its results revealed a significant effect of medium size, indicating that primary dystonia is associated with moderate performance deficits on the WCST. Building on this finding, we conducted an event-related potential (ERP) study to elucidate the cognitive and neural mechanisms underlying executive dysfunction in primary dystonia. Eighteen patients with blepharospasm, a common form of primary focal dystonia, and 34 healthy matched controls completed a computerized version of the WCST. We specifically compared indicators of two distinct components of executive functioning: set shifting and rule inference. On a behavioral level, blepharospasm patients seemed to have particular difficulty integrating information to infer the correct task rule. In addition, P3a amplitude (as an electrophysiological marker of rule-inference processes) was selectively attenuated in blepharospasm patients. Executive dysfunction in blepharospasm can thus rather be attributed to a rule-inference deficit, whereas set-shifting abilities appear to be relatively unaffected by the disease. Moreover, P3a amplitude attenuation was related to disease duration, indicating that this ERP might serve as a neural indicator of disease progression and executive dysfunction in primary dystonia. These results demonstrate for the first time that pathophysiological alterations in primary dystonia might affect cortical activation for executive functioning. PMID- 27376934 TI - [Supported Housing in Families - Alternative to Residential Care for Patients with Severe Mental Illness]. PMID- 27376935 TI - [Supported Employment - A Wrong Policy for Germany? - Pro]. PMID- 27376936 TI - [Supported Employment - A Wrong Policy for Germany? - Contra]. PMID- 27376937 TI - [Not Available]. PMID- 27376938 TI - [Not Available]. PMID- 27376939 TI - Landscape Visual Quality and Meiofauna Biodiversity on Sandy Beaches. AB - Sandy beaches are central economic assets, attracting more recreational users than other coastal ecosystems. However, urbanization and landscape modification can compromise both the functional integrity and the attractiveness of beach ecosystems. Our study aimed at investigating the relationship between sandy beach artificialization and the landscape perception by the users, and between sandy beach visual attractiveness and biodiversity. We conducted visual and biodiversity assessments of urbanized and semiurbanized sandy beaches in Brazil and Uruguay. We specifically examined meiofauna as an indicator of biodiversity. We hypothesized that urbanization of sandy beaches results in a higher number of landscape detractors that negatively affect user evaluation, and that lower-rated beach units support lower levels of biodiversity. We found that urbanized beach units were rated lower than semiurbanized units, indicating that visual quality was sensitive to human interventions. Our expectations regarding the relationship between landscape perception and biodiversity were only partially met; only few structural and functional descriptors of meiofauna assemblages differed among classes of visual quality. However, lower-rated beach units exhibited signs of lower environmental quality, indicated by higher oligochaete densities and significant differences in meiofauna structure. We conclude that managing sandy beaches needs to advance beyond assessment of aesthetic parameters to also include the structure and function of beach ecosystems. Use of such supporting tools for managing sandy beaches is particularly important in view of sea level rise and increasing coastal development. PMID- 27376940 TI - Correlation of tunnel widening and tunnel positioning with short-term functional outcomes in single-bundle anterior cruciate ligament reconstruction using patellar tendon versus hamstring graft: a prospective study. AB - OBJECTIVE: To study the correlation between tunnel widening and tunnel position with short-term functional outcomes post-ACL reconstruction with patellar tendon and hamstring autografts in young adults. MATERIALS AND METHODS: A total of 33 patients who underwent ACL reconstruction between October 2013 and February 2015 were included and followed up for 6 months. A standardized surgical technique was used for each graft type. Intra-op arthroscopy findings and drilled tunnel diameters were noted. They were followed up for 3 and 6 months. Radiological assessment was done at 3 and 6 months with clinical score assessment at 6 months. RESULTS: At 6 months, clinical scores were comparable in both groups. Tunnel widening in both femoral and tibial tunnel at 3 and 6 months were significantly higher in STG group (p values <0.05). The rate of widening was higher in 0-3 months and reduced in 3-6 months. There was statistically significant negative correlation between femoral tunnel widening by CT and IKDC score at 6 months (p value 0.049). We found a positive correlation between posterior positioning of femoral tunnel and Lysholm and IKDC scores. The correlation with Lysholm scores was statistically significant (p value 0.046). CONCLUSION: To conclude, tunnel widening is more with hamstrings graft. Femoral tunnel widening has significant negative correlation with that of IKDC scores at 6 months. Posterior femoral tunnel positioning and Lysholm scores at 6 months had significant correlation. PMID- 27376941 TI - Reversible sinus node injury during circumferential pulmonary vein ablation. PMID- 27376942 TI - Differences in drought- and freeze-induced embolisms in deciduous ring-porous plant species in Japan. AB - MAIN CONCLUSION: Deciduous ring-porous species in Japan shed all of their leaves under severe water stress before large vessels in earlywood are embolized, and embolization take place during winter. Water in deciduous ring-porous species is mainly conducted upward via large earlywood vessels of the current year. Water columns in large vessels are vulnerable to drought-induced and freeze stress induced embolisms. Although a vulnerability curve can be created to estimate the hydraulic capacity of plants, it remains unclear why the loss of conductivity in potted plants of ring-porous species does not reach 100 % under severe drought stress. In this study, two deciduous ring-porous species in Japan (Kalopanax septemlobus and Toxicodendron trichocarpum) were used to explain the species specific pattern in the water-conducting pathway of the stem. We monitored and visualized the spatial distribution of xylem embolisms in the stem of K. septemlobus saplings under drought stress and freeze stress using compact magnetic resonance imaging and cryo-scanning microscopy. In addition, we evaluated the water ascent in the stems of both species using a dye uptake method. Although embolisms of large vessels were observed under drought stress and in winter, all leaves were dropped to avoid fatal water loss after embolization of some large vessels. In contrast, all large vessels were embolized in winter. Larger-diameter vessels of latewood in T. trichocarpum tended to function in trees growing in the warm temperate zone. Thus, our results suggest that the unclear curve may be derived from a discrepancy between leaf water potential and actual water potential in the xylem under severe drought stress. The frequency of xylem embolisms in deciduous ring-porous species in Japan mainly depends on the number of freeze-thaw cycles. PMID- 27376943 TI - A monocentric retrospective study comparing pulse cyclophosphamide therapy versus low dose rituximab in the treatment of refractory autoimmune hemolytic anemia in adults. AB - This retrospective study aims at confirming the efficacy and safety of low dose rituximab and pulse cyclophosphamide in the treatment of refractory AIHA in adults and making comparison of the two. Forty-nine adult patients with refractory AIHA have been enrolled. Results showed low dose rituximab combined with steroid therapy (group B) got more CR (78.9 %, 15/19) compared to that in intermittent intravenous cyclophosphamide combined with steroid therapy (group A) (42.1 %, 8/19) (P = 0.04) at 6 months after treatment. The hemoglobin level in group B was higher than group A at the time point of 1 month (P = 0.02) after treatments. The RFS in group A was 87.9 % at 6 months and 82.7 % at 12 months, which were no significant difference with group B (91.1 % at 6 months and 86.0 % at 12 months) (P = 0.81). Both the two therapies were well tolerated with pulmonary infections as the most common side effects. In conclusion, low dose rituximab combined with steroid therapy presents to be a better choice in the treatment of refractory AIHA in adults comparing with pulse cyclophosphamide therapy. PMID- 27376944 TI - Efficacy of rabbit antithymocyte globulin as first-line treatment of severe aplastic anemia: an Asian multicenter retrospective study. AB - Due to the unavailability of horse antithymocyte globulin (ATG) in many markets worldwide, patients with severe aplastic anemia (SAA) are limited to the use of rabbit ATG. We aimed to analyze hematologic response and overall survival (OS) of Asian patients treated with rabbit ATG as first-line therapy of SAA. We retrospectively reviewed the medical records of 97 consecutive patients who received rabbit ATG as first-line treatment of SAA from 2006 to 2012 at centers in four Asian countries. The primary endpoint was 6- and 12-month overall response rates (ORR) for patients receiving rabbit ATG within the recommended dose range (2.5-3.75 mg/kg/day). Secondary endpoints included ORR in patients receiving any dose of rabbit ATG and 2-year OS. For patients who received rabbit ATG within the recommended dose range, 6- and 12-month ORRs were 17.4 and 63.6 %, respectively. For patients who received any dose of rabbit ATG, 6- and 12-month ORRs were 24.3 and 68.6 %, respectively. The 2-year OS rate was 86.3 %. Rabbit ATG is effective for treatment of SAA in Asian patients. The 12-month ORR and 2 year OS with rabbit ATG were comparable to historical results obtained with horse ATG. PMID- 27376945 TI - Prevalence of 'Candidatus Accumulibacter phosphatis' type II under phosphate limiting conditions. AB - P-limitation in enhanced biological phosphorus removal (EBPR) systems fed with acetate, has generally been considered as a condition leading to enrichment of organisms of the genotype' Candidatus Competibacter phosphatis' expressing the glycogen-accumulating organisms (GAO) phenotype. Recent studies have demonstrated in short-term experiments that organisms of the genotype 'Candidatus Accumulibacter phosphatis' clade I and II, known to express the polyphosphate accumulating organisms (PAO) phenotype can switch to the GAO phenotype when poly P is absent, but are performing the HAc-uptake at lower kinetic rates, where clade I showed the lowest rates. The objective of this study was to verify whether organisms of the genotype 'Candidatus Accumulibacter phosphatis' can also be enriched under P-limiting conditions while expressing a GAO phenotype and more specifically to see which specific clade prevails. A sequencing batch reactor was inoculated with activated sludge to enrich an EBPR culture for a cultivation period of 128 days (16 times the solids retention time) under P-limiting conditions. A mixed culture was obtained comprising of 49 % 'Candidatus Accumulibacter phosphatis' clade II and 46 % 'Candidatus Competibacter phosphatis'. The culture performed a full GAO metabolism for anaerobic HAc uptake, but was still able to switch to a PAO metabolism, taking up excessive amounts of phosphate during the aerobic phase when it became available in the influent. These findings show that P-limitation, often used as strategy for enrichment of 'Candidatus Competibacter phosphatis', does not always lead to enrichment of only 'Candidatus Competibacter phosphatis'. Furthermore, it demonstrates that 'Candidatus Accumulibacter phosphatis' are able to proliferate in activated sludge systems for periods of up to 128 days or longer when the influent phosphate concentrations are just enough for assimilation purposes and no poly-P is formed. The 'Candidatus Accumulibacter phosphatis' retain the ability to switch to the PAO phenotype, taking up phosphate from the influent as soon as it becomes available. PMID- 27376946 TI - Maladaptive choices by defeated rats: link between rapid approach to social threat and escalated cocaine self-administration. AB - RATIONALE: Intermittent social defeat stress engenders persistent neuroadaptations and can result in later increased cocaine taking and seeking. However, there are individual differences in stress-escalated cocaine self administration behavior, which may be a direct result of individual differences in the manner in which rats experience social defeat stress. OBJECTIVE: The present study dissected the discrete behavioral phases of social defeat and analyzed which behavioral characteristics may be predictive of subsequent cocaine self-administration. METHODS: Male Long-Evans rats underwent nine intermittent social defeat episodes over 21 days in a three-compartment apparatus permitting approach to and escape from a confrontation with an aggressive resident rat. Rats then self-administered intravenous cocaine, which culminated in a 24-h unlimited access "binge." Behaviors during social defeat and cocaine self-administration were evaluated by principal component analysis (PCA). RESULTS: PCA revealed that the latency to enter the threatening environment was highly predictive of later cocaine self-administration during the 24-h binge. This behavior was not associated with other cocaine-predictive traits, such as reactivity to novelty in an open field, saccharin preference, and motor impulsivity. Additionally, there was no effect of latency to enter a threatening environment on physiological measures of stress, including plasma corticosterone and corticotropin releasing factor (CRF) in the extended amygdala. However, latency to enter the threatening environment was negatively correlated with brain-derived neurotropic factor (BDNF) and its receptor, tyrosine kinase B (TrkB) in the hippocampus. CONCLUSION: These data suggest that latency to enter a threatening environment is a novel behavioral characteristic predictive of later cocaine self-administration. PMID- 27376947 TI - Effects of food restriction on expression of place conditioning and biochemical correlates in rat nucleus accumbens. AB - RATIONALE: When ad libitum-fed rats undergo cocaine place preference conditioning (CPP) but are switched to food restriction for testing, CPP becomes resistant to extinction and correlates with phosphorylation of alpha-amino-3-hydroxy-5-methyl 4-isoxazolepropionic acid (AMPA) receptor GluA1 at Ser845 in nucleus accumbens (NAc) core. OBJECTIVES: This study tested whether food restriction increases persistence of morphine CPP and conditioned place aversions (CPA) induced by LiCl and naloxone-precipitated morphine withdrawal. MATERIALS AND METHODS: Ad libitum fed rats were conditioned with morphine (6.0 mg/kg, i.p.), LiCl (50.0/75.0 mg/kg, i.p.), or naloxone (1.0 mg/kg, s.c.) 22 h post-morphine (20.0 mg/kg, s.c.). Half of the subjects were then switched to food restriction. Daily testing resumed 3 weeks later, and brains were harvested when one diet group met extinction criterion. Western analyses probed for pSer845-GluA1, pERK1, and pERK2 in NAc. RESULTS: Food restriction increased persistence of morphine CPP and preference scores correlated with pSer845-GluA1 in NAc core and shell. LiCl CPA was curtailed by food restriction, yet pSer845-GluA1 and pERK2 were elevated in NAc core of food-restricted rats. Food restriction increased persistence of naloxone CPA and elevated pSer845-GluA1 in NAc core and shell, and aversion scores were negatively correlated with pERK1 and pERK2 in NAc core. CONCLUSIONS: These results suggest that food restriction prolongs responsiveness to environmental contexts paired with subjective effects of both morphine and morphine withdrawal. A mechanistic scheme, attributing these effects to upregulation of pSer845-GluA1, but subject to override by CPA-specific, pERK2-mediated extinction learning, is explored to accommodate opposite effects of food restriction on LiCl and naloxone CPA. PMID- 27376948 TI - Pituitary adenylate cyclase-activating polypeptide (PACAP) in the central nucleus of the amygdala induces anxiety via melanocortin receptors. AB - RATIONALE: Anxiety disorders are the most common mental disorders in the USA. Characterized by feelings of uncontrollable apprehension, they are accompanied by physical, affective, and behavioral symptoms. The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor PAC1 (PAC1R) are highly expressed in the central nucleus of the amygdala (CeA), and they have gained growing attention for their proposed role in mediating the body's response to stress. OBJECTIVES: The aim of this study was to evaluate the anxiogenic effects of PACAP in the CeA and its effects on the hypothalamic-pituitary-adrenal (HPA) axis. Furthermore, the mechanism of action of PACAP in the CeA was investigated. METHODS: PACAP was microinfused into the CeA of rats, and its effects in the elevated plus maze (EPM), the defensive withdrawal tests, and plasma corticosterone levels were evaluated. The ability of the melanocortin receptor antagonist SHU9119 to block PACAP effect in the EPM was assessed. RESULTS: Intra-CeA PACAP exerted a dose-dependent anxiogenic effect and activated the HPA axis. In contrast, PACAP microinfused into the basolateral nucleus of the amygdala (BlA) had no effect. Finally, the anxiogenic effect of intra-CeA PACAP was prevented by SHU9119. CONCLUSIONS: These data prove an anxiogenic role for the PACAP system of the CeA and reveal that the melanocortin receptor 4 (MC4R) system of CeA mediates these effects. Our data provide insights into this neuropeptide system as a mechanism for modulating the behavioral and endocrine response to stress and suggest that dysregulations of this system may contribute to the pathophysiology of anxiety-related disorders. PMID- 27376949 TI - Consent Issues in Genetic Research: Views of Research Participants. AB - BACKGROUND: With the arrival of large-scale population-based genomic research studies, such as the Precision Medicine Initiative (PMI), the question of how to best consent participants is significant, and in an era of patient-centered research, few studies have evaluated participants' preferences about re-consent and broad consent. Using quantitative methods, this study evaluates participants' views regarding the acceptability of re-consent and broad consent in subjects from the Participant Issues Project. METHODS: A total of 450 participants were recruited from a cancer genetics registry, including cancer patients, their relatives, and controls. Participants completed a secure online survey. RESULTS: Most participants endorsed re-consent when investigating an unrelated health condition or sharing their de-identified data with an investigator at a different institution. Notification rather than re-consent was preferred when studying a different gene but the same disease. Over 80% of respondents endorsed re-consent when parents of a child gave the original consent and the child has now reached adulthood. Preferences for some scenarios varied by history of cancer at baseline, gender, stage of cancer, or case versus control group. The large majority of participants preferred the option to select broad consent categories of research. CONCLUSION: Understanding research participants' preferences, including their views on the need for re-consent, are critical to the success of the PMI. PMID- 27376951 TI - Biomimetic Immuno-Magnetosomes for High-Performance Enrichment of Circulating Tumor Cells. AB - A novel biomimetic immuno-magnetosome (IMS) is developed by coating a leukocyte membrane (decorated with anti-epithelial cell-adhesion molecule antibody) on a magnetic nanocluster. In addition to the good stability and magnetic controllability, the IMS also exhibits satisfactory binding avidity to circulating tumor cells but stealth property to leukocytes. As a result, rare tumor cells can be effectively enriched with undetectable leukocyte background. PMID- 27376950 TI - Alternative splicing of inner-ear-expressed genes. AB - Alternative splicing plays a fundamental role in the development and physiological function of the inner ear. Inner-ear-specific gene splicing is necessary to establish the identity and maintain the function of the inner ear. For example, exon 68 of Cadherin 23 (Cdh23) gene is subject to inner-ear-specific alternative splicing, and as a result, Cdh23(+ 68) is only expressed in inner ear hair cells. Alternative splicing along the tonotopic axis of the cochlea contributes to frequency tuning, particularly in lower vertebrates, such as chickens and turtles. Differential splicing of Kcnma1, which encodes for the alpha subunit of the Ca(2+)-activated K(+) channel (BK channel), has been suggested to affect the channel gating properties and is important for frequency tuning. Consequently, deficits in alternative splicing have been shown to cause hearing loss, as we can observe in Bronx Waltzer (bv) mice and Sfswap mutant mice. Despite the advances in this field, the regulation of alternative splicing in the inner ear remains elusive. Further investigation is also needed to clarify the mechanism of hearing loss caused by alternative splicing deficits. PMID- 27376952 TI - Examining the Social Benefits Principle in Research with Human Participants. AB - The idea that research with human participants should benefit society has become firmly entrenched in various regulations, policies, and guidelines, but there has been little in-depth analysis of this ethical principle in the bioethics literature. In this paper, I distinguish between strong and weak versions and the social benefits principle and examine six arguments for it. I argue that while it is always ethically desirable for research with human subjects to offer important benefits to society (or the public), the reasonable expectation of substantial public benefit should be a necessary condition for regarding research as ethical only when (a) it imposes more than minimal risks on non-consenting subjects; or (b) it is supported by public resources. PMID- 27376954 TI - Phenotyping GABA transaminase deficiency: a case description and literature review. AB - Gamma-aminobutyric acid transaminase (GABA-T) deficiency is an autosomal recessive disorder reported in only three unrelated families. It is caused by mutations in the ABAT gene, which encodes 4-aminobutyrate transaminase, an enzyme of GABA catabolism and mitochondrial nucleoside salvage. We report the case of a boy, deceased at 12 months of age, with early-onset epileptic encephalopathy, severe psychomotor retardation, hypotonia, lower-limb hyporeflexia, central hypoventilation, and rapid increase in weight and, to a lesser rate, length and head circumference. He presented signs of premature pubarche, thermal instability, and water-electrolyte imbalance. Serum total testosterone was elevated (43.3 ng/dl; normal range <16), as well as serum growth hormone (7.7 ng/ml; normal range <1). Brain magnetic resonance imaging (MRI) showed decreased myelination and generalized brain atrophy, later confirmed by post-mortem examination. ABAT gene sequencing was performed post-mortem, identifying a homozygous variant c.888G > T (p.Gln296His),not previously described. In vitro analysis concluded that this variant is pathogenic. The clinical features of this patient are similar to those reported so far in GABA-T deficiency. However, distinct mutations may have a different effect on enzymatic activity, which potentially could lead to a variable clinical outcome. Clinical investigation aiming for a diagnosis should not end with the patient's death, as it may allow a more precise genetic counselling for the family. PMID- 27376955 TI - Laparoscopic Partial Nephrectomy for Peripelvic Cystic Renal Cell Carcinoma: A Single-Center Experience. AB - OBJECTIVE: The study aimed to report our experiences of laparoscopic and open partial nephrectomies on patients with peripelvic cystic renal cell carcinoma (cRCC). METHODS: From July 2003 and October 2014, 18 patients with suspected peripelvic cRCCs underwent partial nephrectomies via an open or laparoscopic approach at Nanjing Drum Tower Hospital. Patients' perioperative and oncological outcomes were analyzed and compared between the open partial nephrectomy (OPN) and the laparoscopic partial nephrectomy (LPN) groups. RESULTS: Seven patients underwent OPNs, and 11 patients underwent LPNs for their peripelvic lesions. All procedures were performed successfully; no conversion to open surgery was encountered in the LPN group. There was no significant difference between the groups in mean operation time, blood loss, warm ischemia time or complication rates. The mean hospital stay in the LPN group was significantly shorter than in the OPN group (p = 0.004). The mean follow-up of the OPN and LPN group was 95.0 and 65.1 months, respectively. No local recurrence or metastasis has been noted during the follow-up period. CONCLUSIONS: Peripelvic cRCC represents an uncommon variant of RCCs; few cases have been reported addressing peripelvic cRCC treatment. Although technically challenging, LPN is an effective minimally invasive modality for treating peripelvic cRCC in experienced hands. PMID- 27376956 TI - Damage mechanisms at the cement-implant interface of polished cemented femoral stems. AB - The occurrence of damage on polished femoral stems has been widely reported in the literature, and bone cement has been implicated in a tribocorrosive failure process. However, the mechanisms of cement-mediated damage and the impact of cement formulation on this process are not well understood. In this study, 13 Zimmer CPT polished femoral stems, and the corresponding cement specimens were retrieved at revision surgery and analyzed using high-resolution imaging techniques. Surface damage attributed to tribocorrosion was observed on all stems. Corrosion product, in the form of black flaky surface debris, was observed on the surface of cement specimens; both energy-dispersive X-ray spectroscopy and inductively coupled plasma mass spectrometry(ICP-MS) confirmed the presence of cobalt and chromium, with the ICP-MS showing much higher levels of Cr compared to Co when compared to the original stem material. Agglomerates of ZrO2 radiopacifier were also identified on the cement surface and, in some cases, showed evidence of abrasive wear; the size of these particles correlated well with elliptical pitting evident on the surfaces of the corresponding stems. This evidence supports the hypothesis that agglomerates of hard radiopacifier particles within the cement may induce a wear-dominated tribocorrosive interaction at the stem-cement interface that damages the surface of polished CoCr femoral stems. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2027-2033, 2017. PMID- 27376957 TI - Chemical Constituents of the Rare Cliff Plant Oresitrophe rupifraga and Their Antineuroinflammatory Activity. AB - Four new (1 - 4) and thirteen known (5 - 17) compounds were isolated from a rare cliff plant, Oresitrophe rupifraga. Based on spectroscopic evidence, the new structures were established to be [(2S,3R,4R)-4-(4-methoxybenzyl)-2-(4 methoxyphenyl)-tetrahydrofuran-3-yl]methanol (1), (3alpha)-23-(acetyloxy)-3 hydroxyolean-12-en-29-oic acid (2), 3alpha,23-(isopropylidenedioxy)olean-12-en-29 oic acid (3, artifact of isolation), and (3beta,15beta)-3-hydroxycholest-5-en-15 yl beta-d-glucopyranoside (4), respectively. Among the isolates, compounds 1, 4, epieudesmin (7), and 1-O-(9Z,12Z,15Z-octadecatrienoyl)glycerol (17) were found to show significant antineuroinflammatory effects by inhibiting the NO production in lipopolysaccharide (LPS)-stimulated murine BV-2 microglial cells, with IC50 values of 7.21, 9.39, 4.96, and 8.51 MUm, respectively. PMID- 27376959 TI - Thirty-three years of 2-acetyl-1-pyrroline, a principal basmati aroma compound in scented rice (Oryza sativa L.): a status review. AB - Rice is the staple food of around 3 billion people, most of them in Asia which accounts for 90% of global rice consumption. Aromatic rices have been preferred over non-aromatic rice for hundreds of years. They have a premium value in national as well as international market owing to their unique aroma and quality. Many researchers were involved in identifying the compound responsible for the pleasant aroma in aromatic rice in the 20th century. However, due to its unstable nature, 2-acetyl-1-pyrroline (2AP) was discovered very late, in 1982. Buttery and co-workers found 2AP to be the principal compound imparting the pleasant aroma to basmati and other scented rice varieties. Since then, 2AP has been identified in all fragrant rice (Oryza sativa L.) varieties and a wide range of plants, animals, fungi, bacteria and various food products. The present article reviews in detail biochemical and genetic aspects of 2AP in living systems. The site of synthesis, site of storage and stability in plant systems in vivo is of interest. This compound requires more research on stability to facilitate use as a food additive. (c) 2016 Society of Chemical Industry. PMID- 27376958 TI - MiRNA-203 suppresses cell proliferation, migration and invasion in colorectal cancer via targeting of EIF5A2. AB - While it is known that miR-203 is frequently downregulated in many types of human cancer, little is known regarding its expression and functional role in colorectal cancer (CRC). In this study, we aimed to investigate the expression and the potential mechanisms of miR-203 in colorectal cancer. MiR-203 was significantly downregulated in CRC tissues compared with matched normal adjacent tissues. Our clinical data show that decreased miR-203 was associated with an advanced clinical tumor-node-metastasis stage, lymph node metastasis, and poor survival in CRC patients. Furthermore, externally induced expression of miR-203 significantly inhibited CRC cell proliferation and invasion in vitro and in vivo. Mechanistically, we identified EIF5A2 as a direct and functional target of miR 203. The levels of miR-203 were inversely correlated with levels of the EIF5A2 in the CRC tissues. Restoration of EIF5A2 in the miR-203-overexpressing CRC cells reversed the suppressive effects of miR-203. Our results demonstrate that miR-203 serves as a tumor suppressor gene and may be useful as a new potential therapeutic target in CRC. PMID- 27376960 TI - Comparative study of toxicity and biochemical responses induced by sublethal levels of the pesticide azinphosmethyl in two fish species from North-Patagonia, Argentina. AB - Biochemical effects of azinphosmethyl (AZM), an organophosphate pesticide, were determined in gill, brain and muscle tissues of Odontesthes hatcheri and Jenynsia multidentata. The 96-h toxicity was first assessed, estimating lethal concentrations fifty (LC50) of 7 and 30MUgL(-1) AZM for O. hatcheri and J. multidentata, respectively. Considering the LC50, sublethal 96-h static exposures were designed for O. hatcheri (0.1-0.5MUgL(-1) AZM) and J. multidentata (5 10MUgL(-1)AZM) to determine biochemical endpoints. Brain acetylcholinesterase (AchE) was inhibited by AZM in both species, while the buffer enzyme carboxylesterase (CarbE) was not affected in this tissue. Conversely, muscular AchE was not affected but CarbE was augmented by AZM. The enzymes glutathione reductase, glutathione-S-transferase and CarbE were significantly inhibited in O. hatcheri gills but none of them was affected by AZM in J. multidentata gills compared to control. GSH levels were augmented in gills of both species in exposed fish compared to controls and in addition, lipid peroxidation was significantly increased in O. hatcheri gills. Ex vivo histochemical analysis of ROS by fluorescence microscopy was also performed in J. multidentata gills, indicating a significant increase upon exposure to 10MUgL(-1) AZM. Principal component analyses (PCA) were applied, both to the species together or separately. The general analysis demonstrated a clear separation of responses in the two species. For O. hatcheri, the variable that explains the major variation in PC1 is gill catalase and brain AchE in PC2. In J. multidentata in turn, the variable that explains the major variation in PC1 is brain AchE and total oxyradical scavenging capacity in PC2. The toxicity data and biomarker responses obtained for both species were compared to environmental concentrations of AZM detected in superficial water from different points in the Alto Valle region and risk quotients (RQ) were calculated. This approach indicated probable acute effects for O. hatcheri in river and irrigation channels (RQ>0.1), while the risk was unacceptable in drainage superficial water (RQ>1). In contrast, J. multidentata showed minimal risk in river or channel water (RQ<0.1) and probable risk in drainage water (RQ=0.75). We conclude that not only the differential susceptibility of both species to AZM is environmentally relevant, but also that the different biomarkers responding in each case underlie particular pathways stressed by this agrochemical. PMID- 27376961 TI - Impact of molt-disrupting BDE-47 on epidermal ecdysteroid signaling in the blue crab, Callinectes sapidus, in vitro. AB - Polybrominated diphenyl ethers (PBDEs) are environmentally pervasive flame retardants that have been linked with endocrine disruption in a variety of organisms. BDE-47, one of the most prevalent congeners found in aquatic environments, has recently been shown to inhibit crustacean molting, but little is known about the specific mechanism through which molt-inhibition occurs. This study examined whether the inhibitory effect on molting arises from the disruption of hormone signaling in the epidermis using the blue crab, Callinectes sapidus, as the model crustacean. First, we partially sequenced cDNA of N-acetyl beta-glucosaminidase (NAG) from the epidermis, a terminal enzyme in the molting hormone-signaling cascades that is commonly used as the biomarker for ecdysteroid signaling. This partial cDNA sequence was then used to create primers for quantification of NAG gene expression. Then, a new tissue culture technique was developed and dubbed the epidermis-with-exoskeleton (EWE) method, wherein epidermal tissue, along with the overlying exoskeleton, is immersed in a medium of physiologically relevant osmolarity. Using this EWE tissue culture method, we assessed the inducibility of NAG mRNA by 20-hydroxyecdysone (20-HE) in vitro. Exposures to 1MUM 20-HE were found to induce NAG mRNA at a significantly higher level than the control. Using NAG expression as a biomarker for ecdysteroid signaling, the effects of BDE-47 were measured. BDE-47 alone at 100nM and a combination of 1MUM BDE-47 and 1MUM 20-HE were found to significantly increase NAG mRNA. A trend of increasing NAG gene expression in the binary BDE-47 exposure as compared to 1MUM BDE-47 and 1MUM 20-HE alone is suggestive of a synergistic effect of these two chemicals on ecdysteroid signaling in the cultured epidermis. Discussion on the mechanism for inhibition of crustacean molting by BDE-47 is presented. PMID- 27376962 TI - Effects of diadenylate cyclase deficiency on synthesis of extracellular polysaccharide matrix of Streptococcus mutans revisit. AB - An emerging secondary messenger c-di-AMP plays an important role in bacterial physiology. It was reported by Cheng et al. that inactivation of a gene coding for diadenylate cyclase (DAC), a c-di-AMP producing enzyme, resulted in enhanced synthesis of extracellular polysaccharides (EPS) by a cariogenic bacterium, Streptococcus mutans (Cheng et al., 2016). We constructed a similar mutant and observed a completely different effect, the DAC deficiency resulted in a decrease in the production of EPS. Our studies provided the following compelling evidence, (1) the DAC mutant we constructed can be readily complemented for the production of EPS, while the mutant from the Cheng group cannot; (2) Our mutant exhibits the regular pattern of key enzymes that produce EPS, glucosyltransferases (Gtfs), while Cheng et al. reported an irregular pattern, which was inconsistent with their earlier studies. (3) We demonstrated that the response of the DAC mutant to oxidative stress is independent of GtfB, the key enzyme producing EPS, while the Cheng report suggests that overproduction of EPS is a responsive mechanism for the DAC mutant to adapt to the oxidative stress. Therefore, the validity of the relationship between DAC and EPS reported by Cheng et al. warrants further investigation and clarification. PMID- 27376963 TI - Giant Negative Electrocaloric Effects of Hf0.5 Zr0.5 O2 Thin Films. AB - Hafnia (HfO2 )-zirconia (ZrO2 ) solid solution films show giant positive (DeltaT = 13.4 K) and negative (DeltaT = -10.8 K) electrocaloric effects that can be simply controlled by tuning the Hf/Zr ratio. It is expected that the combination of the electrocaloric effects with opposite signs in this lead-free, simple, binary oxide can significantly improve the efficiency of electrocaloric cooling. PMID- 27376964 TI - High Performance and Cost-Effective Direct Methanol Fuel Cells: Fe-N-C Methanol Tolerant Oxygen Reduction Reaction Catalysts. AB - Direct methanol fuel cells (DMFCs) offer great advantages for the supply of power with high efficiency and large energy density. The search for a cost-effective, active, stable and methanol-tolerant catalyst for the oxygen reduction reaction (ORR) is still a great challenge. In this work, platinum group metal-free (PGM free) catalysts based on Fe-N-C are investigated in acidic medium. Post-treatment of the catalyst improves the ORR activity compared with previously published PGM free formulations and shows an excellent tolerance to the presence of methanol. The feasibility for application in DMFC under a wide range of operating conditions is demonstrated, with a maximum power density of approximately 50 mW cm(-2) and a negligible methanol crossover effect on the performance. A review of the most recent PGM-free cathode formulations for DMFC indicates that this formulation leads to the highest performance at a low membrane-electrode assembly (MEA) cost. Moreover, a 100 h durability test in DMFC shows suitable applicability, with a similar performance-time behavior compared to common MEAs based on Pt cathodes. PMID- 27376965 TI - Cryopreserved platelet concentrate transfusions in 43 dogs: a retrospective study (2007-2013). AB - OBJECTIVE: To clinically characterize a group of thrombocytopenic dogs that received cryopreserved platelet concentrate (cPC) transfusion, assess efficacy of cPC treatment in improving patient outcome, and compare treated dogs to a control population of thrombocytopenic dogs that did not receive cPC transfusions. DESIGN: Retrospective study. SETTING: University teaching hospital. ANIMALS: Eighty-six client-owned dogs (43 in treatment group, 43 in control group). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records of thrombocytopenic dogs that received cPC transfusions and those of thrombocytopenic dogs that did not receive cPC (control population) from January 2007 through March 2013 were reviewed. Dogs receiving cPC were statistically more likely than controls to have a platelet trigger for cPC transfusion (P = 0.01), lower platelet count (P = 0.009) and hematocrit at presentation (P = 0.001), and lower hematocrit after cPC (P = 0.02). Although there was a statistically significant increase in platelet count from pre- to post-cPC transfusion (P = 0.002), cPC was not found to be effective in improving clinical bleeding or increasing survival compared to the control group. No other characteristics were statistically different between groups. No dogs receiving cPC had an acute transfusion reaction during hospitalization. CONCLUSIONS: In the population described in this study, cPC was not found to increase survival, but was well tolerated. Controlled, prospective studies are necessary to determine indications for and efficacy of cPC transfusions. PMID- 27376966 TI - Desired response to phototherapy vs photoaggravation in psoriasis: what makes the difference? AB - Psoriasis commonly responds beneficially to UV radiation from natural sunlight or artificial sources. Therapeutic mechanisms include the proapoptotic and immunomodulating effects of UV, affecting many cells and involving a variety of pro- and anti-inflammatory cytokines, downregulating the Th17/IL-23 response with simultaneous induction of regulatory immune cells. However, exposure to UV radiation in a subset of psoriasis patients leads to exacerbation of the disease. We herein shed light on the predisposing factors of photosensitive psoriasis, including genetics (such as HLA-Cw*0602 or CARD14), gender and coexisting photodermatoses such as polymorphic light eruption (PLE) in the context of potential molecular mechanisms behind therapeutic photoresponsiveness or photoaggravation. UV-induced damage/pathogen-associated molecular patterns, damage to self-coding RNA (signalling through Toll-like receptors), certain antimicrobial peptides and/or inflammasome activation may induce innate immunity, leading to psoriasis at the site of UV exposure when there is concomitant, predisposing resistance against UV-induced suppression of the adaptive immune response (like in PLE) that otherwise would act to reduce psoriasis. PMID- 27376967 TI - Synthesis of Polyester Dendritic Scaffolds for Biomedical Applications. AB - Using a well-defined poly(2,2-bis(hydroxymethyl)propanoic acid) dendrimer scaffold, a series of G1 to G3 dendrons is functionalized at the periphery with alkynes to enable "Click" functionalization via the copper-catalyzed alkyne-azide cycloaddition (CuAAC). The resulting dendrons are further functionalized at the core with a dipicolylamine (DPA) moiety to enable radiolabeling with 99m Tc for molecular imaging applications. Efficient CuAAC coupling is achieved using an azide-functionalized triethylene glycol monomethyl ether (TEG-N3 ). Removal of copper from the DPA ligand is successfully performed on G1 and G2 dendrimers prior to radiolabeling with 99m Tc. Radiolabeling of the G3 dendrimer is accomplished via transmetallation of the [CuDPA]2+ ligand with 99m Tc, further demonstrating the feasibility of the synthetic strategies in the preparation of dendritic imaging agents. Subsequent attachment of an acyloxymethyl ketone (AOMK) derivative for targeting of cathepsin B is also explored. Despite demonstrating the ability to ligate multiple AOMK ligands, the AOMK-dendrimer conjugates are not able to bind to cathepsin B, which may be attributed to steric hindrance at the dendrimer periphery. PMID- 27376969 TI - Peripheral Nerve Field Stimulation Therapy for Patients With Thoracic Pain: A Prospective Study. AB - OBJECTIVE: Relative to the number of patients suffering chronic lumbar and cervical pain, fewer patients suffer persistent thoracic pain. Consequently there is less literature, with smaller sample sizes, reporting treatment of this cohort. Here, we assess peripheral nerve field stimulation (PNfS) as a potential treatment for chronic thoracic pain. MATERIALS AND METHODS: This study included 20 consecutive chronic thoracic pain sufferers that responded successfully to PNfS trial. The patients were subsequently implanted with permanent eight-contact electrode linear percutaneous leads within their major area of pain. Patients were followed up at 12 months for outcome reporting. All 20 patients were considered in the statistical analysis, despite removal of three devices prior to follow up. RESULTS: The average baseline pre-treatment Numerical Pain Rating Scale (NPRS) score was 7.75 +/- 1.4. Following PNfS, the mean NPRS score was 2.25 +/-2.14, reflecting a significant average improvement of 5.5 +/- 3.31. Three patients were explanted prior to follow up: the first gained excellent thoracic pain relief but pain at the Implantable Pulse Generator (IPG) site could not be overcome, the second achieved excellent pain relief but the PNfS was removed due to recurrent infection and in the final instance, the intervention offered only poor relief and the device removed. CONCLUSION: PNfS is an effective intervention for intractable disabling thoracic pain, offering sustained and worthwhile pain relief, for the overwhelming majority of the cohort. This may be especially true when considering a combined treatment approach of PNfS and analgesic use to manage remnant pain. PMID- 27376970 TI - Re: Urethral bulking for recurrent urinary stress incontinence after midurethral sling failure. PMID- 27376968 TI - The yeast transcription elongation factor Spt4/5 is a sequence-specific RNA binding protein. AB - The heterodimeric transcription elongation factor Spt4/Spt5 (Spt4/5) tightly associates with RNAPII to regulate both transcriptional elongation and co transcriptional pre-mRNA processing; however, the mechanisms by which Spt4/5 acts are poorly understood. Recent studies of the human and Drosophila Spt4/5 complexes indicate that they can bind nucleic acids in vitro. We demonstrate here that yeast Spt4/5 can bind in a sequence-specific manner to single stranded RNA containing AAN repeats. Furthermore, we show that the major protein determinants for RNA-binding are Spt4 together with the NGN domain of Spt5 and that the KOW domains are not required for RNA recognition. These findings attribute a new function to a domain of Spt4/5 that associates directly with RNAPII, making significant steps towards elucidating the mechanism behind transcriptional control by Spt4/5. PMID- 27376971 TI - Effect of intrinsic angular momentum in the capillary filling dynamics of viscous fluids. AB - In this study, an analytical model is provided to describe the filling dynamics of a capillary filled with a viscous fluid containing spinning particles. The aim is to demonstrate the effect of angular momentum on the capillary filling dynamics of molecular fluids which has not been explored before. The presence of spinning particles generates additional coefficients of viscosity, namely, spin viscosity and vortex viscosity, which couples rotational and translational movements. Three different time stages have been noticed during the capillary filling phenomenon: inertia force dominated, visco-inertial, and viscous dominated regions. The last two regions are found to be mainly affected by the spinning particles. An increase in the spin and vortex viscosities is found to increase the viscous force and thus reduce the front position of the moving liquid. The results of this study are validated using the literature no-angular momentum (NAM) base-case results and an excellent agreement is observed. PMID- 27376972 TI - Comments on the Rebuttal to the criticism on the paper "Application of Mn/MCM-41 as an adsorbent to remove Methyl Blue from aqueous solution". PMID- 27376973 TI - Enhanced photocatalytic activity of degrading short chain chlorinated paraffins over reduced graphene oxide/CoFe2O4/Ag nanocomposite. AB - Short chain chlorinated paraffins have recently attracted great attention because of their environmental persistence and biological toxicity as an important organic pollutant. In this work, reduced graphene oxide/CoFe2O4/Ag (RGO/CoFe2O4/Ag) nanocomposite was prepared and employed for photocatalytic degradation of short chain chlorinated paraffins. The process of photocatalytic degradation of short chain chlorinated paraffins over RGO/CoFe2O4/Ag under visible light (lambda>400nm) was investigated by in situ Fourier transform infrared spectroscopy and the related mechanisms were proposed. An apparent degradation ratio of 91.9% over RGO/CoFe2O4/Ag could be obtained under visible light illumination of 12h, while only about 21.7% was obtained with commercial P25 TiO2 under the same experimental conditions, which demonstrates that the RGO/CoFe2O4/Ag nanocomposite is a potential candidate for effective photocatalytic removal of short chain chlorinated paraffins. PMID- 27376974 TI - Precipitation of anionic emulsifier with ordinary Portland cement. AB - Cement has traditionally been used to accelerate bitumen emulsion breaking in cold mix asphalt and cold recycling asphalt. For cold emulsion mixtures, the mixing stability of bitumen emulsion is a crucial property, because it determines the distribution of bitumen and eventually affects the microstructure and the strength development of asphalt mixtures. Recent studies have proven that the interaction between cement and emulsifiers causes the destabilization of bitumen emulsions. The objective of this study is to understand the interaction between cement particles and rosin emulsifiers. For this purpose, the Ca(2+) ions and rosin emulsifier concentration after filtration were measured to identify the interaction between cement and rosin emulsifiers. The consumed emulsifier increases linearly with the amount of added cement or CaCl2 concentration in the case of diluted rosin emulsifier solutions in which the rosin emulsifier concentration is below the CMC (critical micelle concentration). In the case of concentrated rosin emulsifier solutions (above the CMC), the rosin emulsifier concentration shows a sharp decrease when a certain amount of cement or CaCl2 is added. This study indicates that cement destabilizes anionic bitumen emulsion due to the precipitation of rosin emulsifiers caused by Ca(2+) ions which are released by early cement hydration. Further studies on precipitation behavior have shown that micelles of rosin emulsifier can complex Ca(2+) ions but do not precipitate. These findings explain why slow-setting bitumen emulsions, which contain a higher concentration of emulsifier, show better mixing stability. PMID- 27376975 TI - A predictive model of reverse micelles solubilizing water for solvent extraction. AB - Herein, a minimal model for the common case of W/O solubilization of badly soluble compounds present in an excess phase by reverse micellar aggregates in chemical equilibrium with its single compounds is introduced. A simple model of such liquid-liquid extractions is crucial for obtaining predictive parameter for the modelling of nuclear waste management and hydrometallurgic recycling strategies. The standard Gibbs free energy of aggregation and the concentration of the corresponding aggregate is calculated within a multiple-equilibria approach for a set of aggregate compositions of solute and amphiphilic extractant molecules. This minimal model provides potential surfaces estimating the stability of different aggregate compositions with 6.2kJmol(-1) as a generalized bending constant. The complete concentrations of free and aggregated extractant species as well as the favored aggregation numbers, the polydispersity, the activity of the organic solvent, and the critical concentrations are captured by this thermodynamic model. An increase of the apparent critical micelle concentration for an increasing solute content in the aqueous phase is detected by this method. PMID- 27376976 TI - Te inclusion-induced electrical field perturbation in CdZnTe single crystals revealed by Kelvin probe force microscopy. AB - To understand the effects of tellurium (Te) inclusions on the device performance of CdZnTe radiation detectors, the perturbation of the electrical field in and around Te inclusions was studied in CdZnTe single crystals via Kelvin probe force microscopy (KPFM). Te inclusions were proved to act as lower potential centers with respect to surrounding CdZnTe matrix. Based on the KPFM results, the energy band diagram at the Te/CdZnTe interface was established, and the bias-dependent effects of Te inclusion on carrier transportation is discussed. PMID- 27376977 TI - Knowledge, attitudes and awareness regarding fertility preservation among oncologists and clinical practitioners in Lebanon. AB - Fertility preservation (FP) aims to help individuals overcome the infertility associated with cancer treatments such as chemotherapy and radiation. The objective of this study was to assess the awareness, attitudes and knowledge of oncologists' and clinical practitioners' (CPs) about fertility preservation and its options in Lebanon. This was a cross-sectional study with surveys carried out between March 2012 and February 2013 on CPs at the American University of Beirut Medical Centre and Saint Jude's Children Cancer Centre as well as all registered oncologists in Lebanon. Ninety percent of CPs (n = 88) and 94% of oncologists (n = 53) agreed that fertility preservation should be discussed with patient before their cancer treatment. Our data showed a gender bias in relation to patients being informed of their FP options, as well as conflicting knowledge of FP options available in Lebanon among oncologists. The CPs were more likely to have accurate knowledge of FP options and treatment than oncologists. A proactive approach is required to: (1) increase the awareness and knowledge of FP; (2) improve attitudes towards FP; and (3) encourage its communication between CPs, oncologists and patients in Lebanon. Increased education programs, awareness campaigns and development of dedicated FP centres are needed. PMID- 27376978 TI - Solitary fibrous tumor of the pleura with associated Doege-Potter syndrome. AB - Doege-Potter syndrome is a paraneoplastic syndrome characterized by tumor associated hypoglycemia secondary to a solitary fibrous tumor of the pleura. We present a case of an 84-year-old man, who presented with acute mental confusion and therapy-resistant hypoglycemia. Diagnostic imaging revealed a large sharply defined pleural tumor based on the left diaphragm, after surgical resection the diagnosis was made of a malignant solitary fibrous tumor of the pleura and restoration of the glucose homeostasis was observed. PMID- 27376979 TI - The molecularization of identity: science and subjectivity in the 21st century. AB - Recent advances in biological and computational technologies are changing the way different social groups imagine race, gender, kinship, citizenship and disease risk. Existing taxonomies are being displaced or reconfigured, impacting the ways in which people are governed, how lives are lived, how groups are known and how power is exercised. Herein we report on a two-day international symposium that we co-organized, titled 'The molecularization of identity: science and subjectivity in the 21st century,' that was held on 29-30 April 2016 at the Program on Science, Technology and Society, at Harvard University. The symposium drew upon the tools and expertise from multiple disciplines and diverse geographical regions and consisted of 24 original research presentations and an interdisciplinary roundtable. Specific attention was paid to the bioethical, material and lived dimensions of recent developments in molecular technologies, and discussions interrogated the complex ways in which the 'molecular realm' is an emerging site for constituting human identities in the 21st century. Herein we summarize some of the key findings of the conference and raise three further issues for practitioners and researchers to consider in relation to the broader impact of genetics research. Namely: transnational governance of emerging biotechnologies; representation of different interest groups in policy decisions; and rights of access to emerging technologies. PMID- 27376980 TI - Effect of Intestinal Flora on Protein Expression of Drug-Metabolizing Enzymes and Transporters in the Liver and Kidney of Germ-Free and Antibiotics-Treated Mice. AB - Dysbiosis (alteration of intestinal flora) is associated with various host physiologies, including diseases. The purpose of this study was to clarify the effect of dysbiosis on protein expression levels in mouse liver and kidney by quantitative proteomic analysis, focusing in particular on drug-metabolizing enzymes and transporters in order to investigate the potential impact of dysbiosis on drug pharmacokinetics. Germ-free (GF) mice and antibiotics-treated mice were used as dysbiosis models. Expression levels of 825 and 357 proteins were significantly changed in the liver and kidney, respectively, of GF mice (vs specific-pathogen-free mice), while 306 and 178 proteins, respectively, were changed in antibiotics-treated mice (vs vehicle controls). Among them, 52 and 16 drug-metabolizing enzyme and transporter proteins were significantly changed in the liver and kidney, respectively, of GF mice, while 25 and 8, respectively were changed in antibiotics-treated mice. Expression of mitochondrial proteins was also changed in the liver and kidney of both model mice. In GF mice, Oatp1a1 was decreased in both the liver and kidney, while Sult1a1 and two Cyp enzymes were increased and Gstp1, four Cyp enzymes, three Ces enzymes, Bcrp1, and Oct1 were decreased in the liver. In antibiotics-treated mice, Cyp51a1 was increased and three Cyp enzymes, Bcrp1, and Bsep were decreased in the liver. Notably, the expression of Cyp2b10 and Cyp3a11 was greatly decreased in the liver of both models. Cyp2b activity in the liver microsomal fraction was also decreased. Our results indicate that dysbiosis changes the protein expression of multiple drug metabolizing enzymes and transporters in the liver and kidney and may alter pharmacokinetics in the host. PMID- 27376981 TI - Thorium Compounds with Bonds to Sulfur or Selenium: Synthesis, Structure, and Thermolysis. AB - Thorium chalcogenolates Th(ER)4 (E = S, Se; R = Ph, C6F5) form pyridine complexes with a variety of coordination numbers. Four compounds, (py)4Th(SPh)4, (py)3Th(SePh)4, (py)3Th(SC6F5)4, and (py)4Th(SeC6F5)4, have been isolated and characterized by spectroscopic methods and low-temperature single crystal X-ray diffraction. Two of the products, (py)4Th(SPh)4 and (py)4Th(SeC6F5)4, have classic eight coordinate A4B4 square-antiprism geometries. The SePh compound is the only seven coordinate (4Se, 3N) product, and the fluorinated thiolate is distinctive in that the structure contains two dative interactions between Th and fluoride, to give a nine coordinate (3N, 4S, 2F) structure. The EPh compounds decompose thermally to give ThE2 and EPh2, while the fluorinated compounds give primarily ThF4, E2(C6F5)2, and E(C6F5)2. PMID- 27376982 TI - C-type natriuretic peptide is closely associated to obesity in Caucasian adolescents. AB - CNP is a natural regulator of adipogenesis playing a role in the development of obesity in childhood. Aim of the study was to evaluate CNP plasma levels in normal-weight (N), overweight (OW) and obese adolescents (O). Eighty two subjects (age:12.8+/-2.4, years) without cardiac dysfunction were enrolled and CNP plasma levels were measured by RIA. NT-proBNP, MR-proANP, AGEs, reactive hyperemia index (RHI) and standard clinical chemistry parameters were also measured. O and OW adolescents had higher values of BMI and fat mass than N. CNP levels were significantly lower in OW:4.79[3.29-21.15] and O:3.81[1.55-13.4] than in N:13.21[7.6-37.8]; p<0.0001N vs O, p=0.0003N vs OW). LogCNP values correlated significantly and inversely with BMI z-score, FM%, TF% and circulating levels of CRP, insulin, total cholesterol, LDL, and triglycerides, in addition to an inverse relationship with skin AGEs and a direct correlation with RHI. LogCNP was also inversely associated with LogNT-proBNP and LogMR-proANP values. Using ROC analysis the risk of obesity resulted significantly (p?0.0001) associated with CNP values (AUC=0.9724). These results suggest that CNP may play a more important role than BNP and ANP related peptides, as risk marker of obesity, in addition to its involvement in adipogenesis and endothelial dysfunction. PMID- 27376983 TI - Quantification of specific IgE antibodies in immediate drug hypersensitivity: More shortcomings than potentials? AB - BACKGROUND: For many physicians, quantification of serum drug-specific IgE (sIgE) antibodies constitutes the first measure in the diagnostic approach of immediate drug hypersensitivity reactions (IDHR). AIM: To review the accuracy and limitations of the main drug-sIgE tests, especially those that are commercially available. METHODS: A literature search was conducted, using the key-words allergy, diagnosis, drugs, hypersensitivity, specific IgE antibodies; this was complemented by the authors' own experience. RESULTS: The drugs that have mostly been studied appeared to be beta-lactam antibiotics, neuromuscular blocking agents (NMBA) and morphine, the latter as a biomarker for sensitisation to substituted ammonium structures that constitute the major epitope of NMBA. For beta-lactams sensitivity and specificity varied between 0-85% and 52-100%, respectively. For NMBA, sensitivity and specificity varied between 38.5-92% and 92-100%, respectively. With respect to sIgE to morphine it appears this drug to be a sensitive biomarker for sensitisation to rocuronium and suxamethonium but not for atracurium. However, sIgE morphine should not be applied in isolation to diagnose IDHR to NMBA nor opiates. CONCLUSIONS: Although drug-sIgE assay can provide valuable information they should not be performed in isolation to establish correct diagnosis, as their predictive value is not per se absolute. Larger comprehensive studies are urgently required to determine the accuracy of drug-sIgE assays. PMID- 27376984 TI - Dedifferentiated Schwann Cell Precursors Secreting Paracrine Factors Are Required for Regeneration of the Mammalian Digit Tip. AB - Adult mammals have lost multi-tissue regenerative capacity, except for the distal digit, which is able to regenerate via mechanisms that remain largely unknown. Here, we show that, after adult mouse distal digit removal, nerve-associated Schwann cell precursors (SCPs) dedifferentiate and secrete growth factors that promote expansion of the blastema and digit regeneration. When SCPs were dysregulated or ablated, mesenchymal precursor proliferation in the blastema was decreased and nail and bone regeneration were impaired. Transplantation of exogenous SCPs rescued these regeneration defects. We found that SCPs secrete factors that promote self-renewal of mesenchymal precursors, and we used transcriptomic and proteomic analysis to define candidate factors. Two of these, oncostatin M (OSM) and platelet-derived growth factor AA (PDGF-AA), are made by SCPs in the regenerating digit and rescued the deficits in regeneration caused by loss of SCPs. As all peripheral tissues contain nerves, these results could have broad implications for mammalian tissue repair and regeneration. PMID- 27376985 TI - Size-selective toxicity effects of the antimicrobial tylosin on estuarine phytoplankton communities. AB - The purpose of this study was to determine the lethal and sublethal effects of the antimicrobial tylosin on natural estuarine phytoplankton communities. Bioassays were used in experimental treatments with final concentrations of 5 to 1000 MUg tylosin l(-1). Maximum percent inhibition ranged from 57 to 85% at concentrations of 200-400 MUg tylosin l(-1). Half maximum inhibition concentrations of tylosin were ca. 5x lower for small phytoplankton (<20 MUm) relative to larger phytoplankton (>20 MUm) and suggests that small phytoplankton are more sensitive to tylosin exposure. Sublethal effects occurred at concentrations as low as 5 MUg tylosin l(-1). Environmental concentrations of tylosin (e.g., 0.2-3 MUg l(-1)) may have a significant sublethal effect that alters the size structure and composition of phytoplankton communities. The results of this study highlight the potential importance of cell size on toxicity responses of estuarine phytoplankton. PMID- 27376986 TI - Quality screening for air quality monitoring data in China. AB - Particulate matter data obtained from the national air quality monitoring network in China has become an essential and critical data source for many current and forthcoming studies as well as the formulation and implementation of air pollution regulatory policies on particulate matter (PM2.5 and PM10). However, the quality control of this data is dubitable and can affect many future studies and policies. This study identifies and elucidates two significant quality control issues with the data. They are PM2.5 levels exceeding concurrent co located PM10 levels and the registration of same concentrations for consecutive hours at some stations. Future studies utilizing particulate matter data need to acknowledge and address these issues to ensure accurate and reliable results. PMID- 27376987 TI - High-resolution imaging of labile phosphorus and its relationship with iron redox state in lake sediments. AB - A thorough understanding of the labile status and dynamics of phosphorus (P) and iron (Fe) across the sediment-water interface (SWI) is essential for managing internal P release in eutrophic lakes. Fe-coupled inactivation of P in sediments is an important factor which affects internal P release in freshwater lakes. In this study, two in-situ high-resolution diffusive gradients in thin films (DGT) techniques, Zr-Oxide DGT and ZrO-Chelex DGT, were used to investigate the release characteristics of P from sediments in a large freshwater lake (Dongting Lake, China; area of 2691 km2) experiencing a regional summer algal bloom. Two dimensional distributions of labile P in sediments were imaged with the Zr-Oxide DGT without destruction of the original structure of the sediment layer at four sites of the lake. The concentration of DGT-labile P in the sediments, ranging from 0.007 to 0.206 mg L-1, was highly heterogeneous across the profiles. The values of apparent diffusion flux (Fd) and release flux (Fr) of P varied between 0.027-0.197 mg m-2 d-1 and 0.037-0.332 mg m-2 d-1, respectively. Labile P showed a high and positive correlation (p < 0.01) with labile Fe(II) in the profiles, providing high-resolution evidence for the key role of Fe-redox cycling in labile P variation in sediments. PMID- 27376988 TI - Efficient arsenate removal by magnetite-modified water hyacinth biochar. AB - Magnetic biochars (MW) prepared by chemical co-precipitation of Fe(2+)/Fe(3+) on water hyacinth biomass followed by pyrolysis exhibited important potential in aqueous As(V) elimination. In comparison, MW2501 outperformed other MWs and exhibited the highest As(V) sorption capacity which was estimated to be 7.4 mg g( 1) based on Langmuir-Freundlic model. With solution pH ranging from 3 to 10, As(V) removal efficiency by MW2501 kept stable and consistently higher than 90%. Besides, ~100% removal of 0.5 mM As(V) can be obtained in the presence of P <= 0.1 mM or Cr/Sb <= 0.5 mM, indicating a wide applicability of MW2501 for treatment of As-containing water. The predominance of Fe3O4 on MW2501 surface was evidenced by XRD. Ligand exchange between As(V) anion and the hydroxylated surface of Fe3O4 as well as H bond was largely responsible for As(V) sorption as suggested by FTIR. XPS analysis further revealed the dominance of As(V) in the sorbed As on MW2501 surface with co-occurrence of a minor proportion of As(III) (11.45%). In parallel, oxidative transformation of Fe3O4 to Fe2O3 was also suggested by XPS. By a lab-scale column test, the potential and suitability of MW2501 in As-containing water treatment was further confirmed, which could also provide an alternative way to manage and utilize this highly problematic invasive species. PMID- 27376989 TI - Preliminary evidence of nutrients release from sediment in response to oxygen across benthic oxidation layer by a long-term field trial. AB - In aquatic ecosystems, ecological processes such as organic matter mineralization and nutrient cycling are regulated by benthic O2 in sediments, and application of in situ techniques in field environments has the potential to better define the links between O2 dynamics and the unique biogeochemical phenomena occurring in these regions. The effects of benthic O2 on sediment nutrients release were identified on the basis of field specific observations conducted over one and a half years at Taihu Lake. Sediment dredging (SD) practices have sharply reworked the benthic boundary oxidation layer, and the oxygen penetration depth (OPD) in the SD responded as expected to the new-born surface, increasing immediately (7.5 +/- 0.8 - 10.5 +/- 0.6 mm) after dredging, then further increasing with an unusually high heterogeneity when a significant submersed macrophytes (SM) coverage of about 40% was implemented. Multiple correlation analysis revealed that OPD was responsible for PO43- and NH4+ release. A lower benthic oxygen flux was immediately observed in dredging-related sediments in the case of dredging compared to SM or the control (CK), which suggested that oxygen demand is low in the uppermost sediments because of the degradable fresh organic carbon removal. SD and SDSM implementation was most successful at continuously reducing the size of PO43- released from sediments over one and a half years, and a significant seasonal-dependent release was also observed. The direction of flux was consistent among SD and SDSM, suggesting the potential to reduce internal PO43- release even further with the invasion of SM communities. Our results indicated that ecological engineering practices could alleviate internal nutrient loads from the contaminated bottom sediment, which was probably in positive response to benthic oxygen changes. PMID- 27376990 TI - Metal enrichment and lead isotope analysis for source apportionment in the urban dust and rural surface soil. AB - To understand the metal accumulation in the environment and identify its sources, 29 different metal contents and lead (Pb) isotope ratios were determined for 40 urban dust samples, 36 surface soil samples, and one river sediment sample collected in the municipality of Beijing, China. Results showed that cadmium, copper (Cu), mercury, Pb, antimony (Sb), and zinc demonstrated to be the typical urban contaminants and mostly influenced by the adjacent human activities with higher content to background ratios and SD values. Among the 29 metal elements investigated, Cu and Sb were found to be the most distinct elements that were highly affected by the developing level and congestion status of the cities with much higher contents in dust in more developed and congested cities. There was a relatively wider range of Pb isotope ratios of country surface soil than those of urban dust. The results of source identification based on Pb isotope ratios showed that coal combustion was the first largest Pb source and vehicle exhaust was the second largest source. The sum of them accounted for 74.6% mass proportion of overall Pb pollution on average. The surface soil sample collected at an iron mine had the highest (204)Pb/(206)Pb, (207)Pb/(206)Pb, and (208)Pb/(206)Pb ratios indicating ore had much higher ratios than other sources. The fine particle subsamples had higher (204)Pb/(206)Pb, (207)Pb/(206)Pb, and (208)Pb/(206)Pb ratios than the coarse particle subsamples indicating more anthropogenic sources of coal combustion and vehicle exhaust for fine particles and more background influence for coarse particles. These results help with pinpointing the major Pb sources and applying suitable measures for the target sources. PMID- 27376991 TI - Bioassay-directed identification of toxicants in sediments of Liaohe River, northeast China. AB - Contaminants accumulated in sediments may directly harm benthic organisms, however, the specific contaminants responsible for adverse effects have been poorly described. In this study, a bioassay-directed analysis combined with toxicity tests and chemistry analysis was conducted to determine the compounds eliciting the greatest toxicological effect in the sediments in Liaohe River, northeast China. A total of 24 sediment samples were examined to determine their acute toxicity to midge Chironomus tentans (C. tentans). Of these samples, 15 exhibited significant toxicity, with a mortality of 23%-93% (p < 0.05). Numerous contaminants, including 16 polycyclic aromatic hydrocarbons, 32 polychlorinated biphenyls, 20 organochlorine pesticides, 6 organophosphate pesticides, 8 pyrethroids, and 5 heavy metals were analyzed. On the basis of toxic unit (TU) analysis results, pyrethroids may contribute to the toxicity of 9 of the 15 toxic samples with concentrations of >1 TU. The significant correlation between the TUs of pyrethroids and the mortality of C. tentans (r2 = 0.74, p < 0.01) confirmed the major role of pyrethroids in toxicity. The selected sediment samples responding to piperonyl butoxide and low temperature with the increased toxicity exhibited the characteristics of pyrethroids. The bioassay-based screening framework provided strong evidence that pyrethroids were the primary cause of sediment toxicity in Liaohe River. Further studies should therefore be conducted to regulate this important class of pollutants. PMID- 27376992 TI - Potential toxicity of improperly discarded exhausted photovoltaic cells. AB - Low tech photovoltaic panels (PVPs) installed in the early '80s are now coming to the end of their life cycle and this raises the problem of their proper disposal. As panels contain potentially toxic elements, unconventional, complex and costly procedures are required to avoid environmental health risks and in countries where environmental awareness and economic resources are limited this may be especially problematic. This work was designed to investigate potential risks from improper disposal of these panels. To accomplish this aim an exhausted panel was broken into pieces and these were placed in water for 30 days. The resulting leached solution was analyzed to determine chemical release or used in toto, to determine its potential toxicity in established tests. The end points were seed germination (on Cucumis sativus and Lens culinaris) and effects on early development in three larval models: two crustaceans, Daphnia magna and Artemia salina, and the sea urchin Paracentrotus lividus. Our results show that the panels release small amounts of electrolytes (Na, Ca and Mg) into solution, along with antimony and manganese, with a concentration under the accepted maximum contaminant level, and nickel at a potentially toxic concentration. Developmental defects are seen in the plant and animal test organisms after experimental exposure to the whole solution leached from the broken panel. The toxic effects revealed in in vitro tests are sufficient to attract attention considering that they are exerted on both plants and aquatic animals and that the number of old PVPs in disposal sites will be very high. PMID- 27376993 TI - Limited recovery of soil microbial activity after transient exposure to gasoline vapors. AB - During gasoline spills complex mixtures of toxic volatile organic compounds (VOCs) are released to terrestrial environments. Gasoline VOCs exert baseline toxicity (narcosis) and may thus broadly affect soil biota. We assessed the functional resilience (i.e. resistance and recovery of microbial functions) in soil microbial communities transiently exposed to gasoline vapors by passive dosing via headspace for 40 days followed by a recovery phase of 84 days. Chemical exposure was characterized with GC-MS, whereas microbial activity was monitored as soil respiration (CO2 release) and soil bacterial growth ([(3)H]leucine incorporation). Microbial activity was strongly stimulated and inhibited at low and high exposure levels, respectively. Microbial growth efficiency decreased with increasing exposure, but rebounded during the recovery phase for low-dose treatments. Although benzene, toluene, ethylbenzene and xylene (BTEX) concentrations decreased by 83-97% during the recovery phase, microbial activity in high-dose treatments did not recover and numbers of viable bacteria were 3-4 orders of magnitude lower than in control soil. Re-inoculation with active soil microorganisms failed to restore microbial activity indicating residual soil toxicity, which could not be attributed to BTEX, but rather to mixture toxicity of more persistent gasoline constituents or degradation products. Our results indicate a limited potential for functional recovery of soil microbial communities after transient exposure to high, but environmentally relevant, levels of gasoline VOCs which therefore may compromise ecosystem services provided by microorganisms even after extensive soil VOC dissipation. PMID- 27376994 TI - Reconstructing the Chernobyl Nuclear Power Plant (CNPP) accident 30 years after. A unique database of air concentration and deposition measurements over Europe. AB - 30 years after the Chernobyl Nuclear Power Plant (CNPP) accident, its radioactive releases still remain of great interest mainly due to the long half-lives of many radionuclides emitted. Observations from the terrestrial environment, which hosts radionuclides for many years after initial deposition, are important for health and environmental assessments. Furthermore, such measurements are the basis for validation of atmospheric transport models and can be used for constraining the still not accurately known source terms. However, although the "Atlas of cesium deposition on Europe after the Chernobyl accident" (hereafter referred to as "Atlas") has been published since 1998, less than 1% of the direct observations of (137)Cs deposition has been made publicly available. The remaining ones are neither accessible nor traceable to specific data providers and a large fraction of these data might have been lost entirely. The present paper is an effort to rescue some of the data collected over the years following the CNPP accident and make them publicly available. The database includes surface air activity concentrations and deposition observations for (131)I, (134)Cs and (137)Cs measured and provided by Former Soviet Union authorities the years that followed the accident. Using the same interpolation tool as the official authorities, we have reconstructed a deposition map of (137)Cs based on about 3% of the data used to create the Atlas map. The reconstructed deposition map is very similar to the official one, but it has the advantage that it is based exclusively on documented data sources, which are all made available within this publication. In contrast to the official map, our deposition map is therefore reproducible and all underlying data can be used also for other purposes. The efficacy of the database was proved using simulated activity concentrations and deposition of (137)Cs from a Langrangian and a Euleurian transport model. PMID- 27376995 TI - The status of organochlorine pesticide contamination in the soils of the Campanian Plain, southern Italy, and correlations with soil properties and cancer risk. AB - The distribution, inventory, and potential risk of organochlorine pesticides (OCPs), including Hexachlorocyclohexanes (HCHs) and Dichlorodiphenyltrichloroethanes (DDTs), and their correlation with soil properties and anthropogenic factors were investigated in soils of the Campanian Plain. The total concentrations of HCHs and DDTs ranged from 0.03 to 17.3 ng/g (geometric mean: GM = 0.05 ng/g), and 0.08-1231 ng/g (GM = 14.4 ng/g), respectively. In general, the concentration of OCPs in farmland and orchards was higher than on land used for non-agricultural purposes. There are significant differences in the concentration of OCPs in the soils across the region, more specifically, the Acerra-Marigliano conurbation (AMC) and Sarno River Basin (SRB) are recognized as severely OCP-contaminated areas. The recent application of technical HCHs and DDTs in large quantities appears unlikely in light of the ratio of alpha-HCH/beta-HCH and p,p'-DDT/p,p'-DDE, and the prohibition of the use of these chemicals in Italy nearly forty years ago. The clear correlation between the concentration of DDTs and organic carbon suggests a typical secondary distribution pattern. The mass inventory of OCPs in soils of the Campanian Plain is estimated to have a GM of 17.3 metric tons. There is no clear evidence linking the impact of geographical distribution of OCPs on the incidence of cancer, and the 95% confidence interval of total incremental lifetime cancer risk (TILCR) data falls below the internationally accepted benchmark value of 1 * 10(-5). PMID- 27376996 TI - Detection of environmental impacts of shrimp farming through multiple lines of evidence. AB - In order to evaluate the impact of semi-intensive shrimp farming, comparisons between Control and Impact areas were made based on multiple lines of evidence using an asymmetrical design. Water and sediment samples were collected in four shrimp farms located in Todos os Santos Bay, Bahia, Brazil. Nutrients, trace elements and macrobenthic assemblages were evaluated using uni- and multivariate analyzes. Significant differences were observed between Impact and Control areas for the water column dataset (i.e., ancillary variables, SPM, dissolved nutrients and major and trace elements in SPM), whereas no significant differences were observed for the chemistry of sediments. Macrobenthic assemblages were negatively affected by shrimp farm activities. Impacted sites presented the lowest abundance, richness and different structure of macrofaunal benthic assemblages. Farms clearly produced negative impacts in the Todos os Santos Bay. This conclusion was only possible to be reached through the use of multiple lines of evidence. Chemistry and benthic assemblages data combined produced a better description of the quality and impacts of the evaluated environments. Different conclusions would have been reached if chemistry and ecology results were studied separately vs. together. PMID- 27376997 TI - Increasing Occurrence of Postoperative Atrial Fibrillation in Contemporary Cardiac Surgery. AB - OBJECTIVE: Patients referred for cardiac surgery are increasingly older, with a higher prevalence of significant comorbidities and undergoing more extensive surgery. The aim of the study was to ascertain the incidence and presentation of postoperative atrial fibrillation in contemporary patients. DESIGN: A prospective single-center study. SETTING: A tertiary academic center. PARTICIPANTS: Between January 2013 and December 2014, 1,356 consecutive patients (72% male, median age 68), including urgent and emergency cases, were analyzed. Preoperative paroxysmal atrial fibrillation was present in 163 (12%) and chronic in 156 (12%) patients. INTERVENTIONS: No interventions. MEASUREMENTS AND MAIN RESULTS: Of the 1,164 patients without chronic atrial fibrillation and surviving at least 5 days, 599 (51%) developed postoperative atrial fibrillation, 43% after bypass, 55% after single valve, 74% after multiple valve, 66% after combined bypass and valve, and 54% after aortic procedures, p<0.001, respectively. In 29%, the duration of postoperative atrial fibrillation was less than 48 hours and did not recur, whereas in 71% the arrhythmia persisted for at least 48 hours or recurred during hospitalization. Patients with postoperative atrial fibrillation were significantly older, had a higher prevalence of previous atrial fibrillation and hypertension, larger left atrium, and required longer hospitalization with increased rates of reoperations and infectious complications. CONCLUSIONS: The authors report high, 10% to 20% greater than previously described, occurrence of postoperative atrial fibrillation in contemporary patients undergoing cardiac surgery. Most patients with postoperative atrial fibrillation experienced prolonged duration or recurrence of the arrhythmia. The type of surgery, advanced age, and previous atrial fibrillation were the most important risk factors. PMID- 27376998 TI - Deaths: Leading Causes for 2014. AB - Objectives-This report presents final 2014 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2014," the National Center for Health Statistics' annual report of final mortality statistics. PMID- 27376999 TI - Patterns of trace element bioaccumulation in jellyfish Rhizostoma pulmo (Cnidaria, Scyphozoa) in a Mediterranean coastal lagoon from SE Spain. AB - The effects of an abandoned mining area, exploited for centuries in the mining district of Cartagena-La Union, result in a continuous supply of heavy metals into the Mar Menor coastal lagoon after rain episodes. As a consequence, concentration of trace elements in water column and sediments of this ecosystem is usually higher than in other areas. For monitoring ecosystem health, this study assessed the ability of Rhizostoma pulmo to bioaccumulate trace elements. A total of 57 individuals were sampled at eight different sampling stations during the summer of 2012. Although the concentrations of different analyzed elements (Al, Ti, Cr, Mn, Fe, Ni, Cu, Zn, As, Cd, Sn, and Pb) were moderate, bioconcentration levels in relation to seawater metal concentration were extremely high. In any case, the use or disposal of these organisms should consider their metal content, because of their potential environmental and health implications. PMID- 27377000 TI - Is existing legislation fit-for-purpose to achieve Good Environmental Status in European seas? AB - Recent additions to marine environmental legislation are usually designed to fill gaps in protection and management, build on existing practices or correct deficiencies in previous instruments. Article 13 of the European Marine Strategy Framework Directive (MSFD) requires Member States to develop a Programme of Measures (PoM) by 2015, to meet the objective of Good Environmental Status (GES) for their waters by 2020. This review explores key maritime-related policies with the aim to identify the opportunities and threats that they pose for the achievement of GES. It specifically examines how Member States have relied on and will integrate existing legislation and policies to implement their PoM and the potential opportunities and difficulties associated with this. Using case studies of three Member States, other external impediments to achieving GES are discussed including uses and users of the marine environment who are not governed by the MSFD, and gives recommendations for overcoming barriers. PMID- 27377001 TI - Estimating the input of submarine groundwater discharge (SGD) and SGD-derived nutrients in Geoje Bay, Korea using (222)Rn-Si mass balance model. AB - In order to evaluate the main source of nutrients for maintaining the high production in shellfish farming bay, we have measured (222)Rn activities and the concentrations of nutrients in stream water, seawater, and coastal groundwater around Geoje Bay, one of the largest cultivation areas of oyster in the southern sea of Korea in April 2013. Using the (222)Rn and Si mass balance model, the residence time of bay seawater was about 5days and the submarine groundwater discharge (SGD) into the bay was estimated to be approximately 1.8*10(6)m(3) d( 1). The SGD-derived nutrient fluxes contributed approximately 54% for DIN, 5% for DIP, and 50% for DSi of total nutrient input entering into the bay. Thus, our results suggest that SGD is the major source of nutrients in Geoje Bay, and SGD derived nutrients are very important to support the biological production of this shellfish farming bay. PMID- 27377002 TI - Dynamic fugacity model for accidental oil release during Arctic shipping. AB - Improved understanding of ecological risk associated with Arctic shipping would help advance effective oil spill prevention, control, and mitigation strategies. Ecological risk assessment involves analysis of a release (oil), its fate, and dispersion, and the exposure and intake of the contaminant to different receptors. Exposure analysis is a key step of the detailed ecological risk assessment, which involves the evaluation of the concentration and persistence of released pollutants in the media of contact. In the present study, a multimedia fate and transport model is presented, which is developed using a fugacity-based approach. This model considers four media: air, water, sediment, and ice. The output of the model is the concentration of oil (surrogate hydrocarbons naphthalene) in these four media, which constitutes the potential exposure to receptors. The concentration profiles can subsequently be used to estimate ecological risk thereby providing guidance to policies for Arctic shipping operations, ship design, and ecological response measures. PMID- 27377003 TI - Benthic assemblages associated with native and non-native oysters are similar. AB - Invasive species can impact native species and alter assemblage structure, which affects associated ecosystem functioning. The pervasive Pacific oyster, Crassostrea gigas, has been shown to affect the diversity and composition of many host ecosystems. We tested for effects of the presence of the invasive C. gigas on native assemblages by comparing them directly to assemblages associated with the declining native European oyster, Ostrea edulis. The presence of both oyster species was manipulated in intertidal and subtidal habitats and reefs were constructed at horizontal and vertical orientation to the substratum. After 12months, species diversity and benthic assemblage structure between assemblages with C. gigas and O. edulis were similar, but differed between habitats and orientation, suggesting that both oyster species were functionally similar in terms of biodiversity facilitation. These findings support evidence, that non native species could play an important role in maintaining biodiversity in systems with declining populations of native species. PMID- 27377004 TI - Corrigendum to "Changes of Nf-kappaB expression in the context of differential EAAT2 level in selected brain structures of rats showing addiction-vulnerable or addiction-resistant phenotype" [Toxicol. Lett. 238 (2015) s382]. PMID- 27377005 TI - Statin-induced myotoxicity is exacerbated by aging: A biophysical and molecular biology study in rats treated with atorvastatin. AB - Statin-induced skeletal muscle damage in rats is associated to the reduction of the resting sarcolemmal chloride conductance (gCl) and ClC-1 chloride channel expression. These drugs also affect the ClC-1 regulation by increasing protein kinase C (PKC) activity, which phosphorylate and close the channel. Also the intracellular resting calcium (restCa) level is increased. Similar alterations are observed in skeletal muscles of aged rats, suggesting a higher risk of statin myotoxicity. To verify this hypothesis, we performed a 4-5-weeks atorvastatin treatment of 24-months-old rats to evaluate the ClC-1 channel function by the two intracellular microelectrodes technique as well as transcript and protein expression of different genes sensitive to statins by quantitative real-time-PCR and western blot analysis. The restCa was measured using FURA-2 imaging, and histological analysis of muscle sections was performed. The results show a marked reduction of resting gCl, in agreement with the reduced ClC-1 mRNA and protein expression in atorvastatin-treated aged rats, with respect to treated adult animals. The observed changes in myocyte-enhancer factor-2 (MEF2) expression may be involved in ClC-1 expression changes. The activity of PKC was also increased and further modulate the gCl in treated aged rats. In parallel, a marked reduction of the expression of glycolytic and mitochondrial enzymes demonstrates an impairment of muscle metabolism. No worsening of restCa or histological features was found in statin-treated aged animals. These findings suggest that a strong reduction of gCl and alteration of muscle metabolism coupled to muscle atrophy may contribute to the increased risk of statin-induced myopathy in the elderly. PMID- 27377006 TI - P-gp, MRP2 and OAT1/OAT3 mediate the drug-drug interaction between resveratrol and methotrexate. AB - The purpose of present study was to investigate the effect of resveratrol (Res) on altering methotrexate (MTX) pharmacokinetics and clarify the related molecular mechanism. Res significantly increased rat intestinal absorption of MTX in vivo and in vitro. Simultaneously, Res inhibited MTX efflux transport in MDR1-MDCK and MRP2-MDCK cell monolayers, suggesting that the target of drug interaction was MDR1 and MRP2 in the intestine during the absorption process. Furthermore, there was a significant decrease in renal clearance of MTX after simultaneous intravenous administration. Similarly, MTX uptake was markedly inhibited by Res in rat kidney slices and hOAT1/3-HEK293 cell, indicating that OAT1 and OAT3 were involved in the drug interaction in the kidney. Additionally, concomitant administration of Res decreased cytotoxic effects of MTX in hOAT1/3-HEK293 cells, and ameliorated nephrotoxicity caused by MTX in rats. Conversely, intestinal damage caused by MTX was not exacerbated after Res treatment. In conclusion, Res enhanced MTX absorption in intestine and decreased MTX renal elimination by inhibiting P-gp, MRP2, OAT1 and OAT3 in vivo and in vitro. Res improved MTX induced renal damage without increasing intestinal toxicity. PMID- 27377007 TI - Proteome-wide measurement of non-canonical bacterial mistranslation by quantitative mass spectrometry of protein modifications. AB - The genetic code is virtually universal in biology and was likely established before the advent of cellular life. The extent to which mistranslation occurs is poorly understood and presents a fundamental question in basic research and production of recombinant proteins. Here we used shotgun proteomics combined with unbiased protein modification analysis to quantitatively analyze in vivo mistranslation in an E. coli strain with a defect in the editing mechanism of leucyl-tRNA synthetase. We detected the misincorporation of a non-proteinogenic amino acid norvaline on 10% of all measured leucine residues under microaerobic conditions and revealed preferential deployment of a tRNA(Leu)(CAG) isoacceptor during norvaline misincorporation. The strain with the norvalylated proteome demonstrated a substantial reduction in cell fitness under both prolonged aerobic and microaerobic cultivation. Unlike norvaline, isoleucine did not substitute for leucine even under harsh error-prone conditions. Our study introduces shotgun proteomics as a powerful tool in quantitative analysis of mistranslation. PMID- 27377008 TI - Generally representative is representative of none: commentary on the pitfalls of IQ test standardization in multicultural settings. AB - OBJECTIVE: The aim of this paper is to address the issue of IQ testing within the multicultural context, with a focus on the adequacy of nationwide population based norms vs. demographically stratified within-group norms for valid assessment purposes. Burgeoning cultural diversity worldwide creates a pressing need to cultivate culturally fair psychological assessment practices. METHOD: Commentary is provided to highlight sources of test-taking bias on tests of intellectual ability that may incur invalid placement and diagnostic decisions in multicultural settings. Methodological aspects of population vs. within-group norming solutions are delineated and the challenges of culturally relevant norm development are discussed. Illustrative South African within-group comparative data are supplied to support the review. A critical evaluation of the South African WAIS-III and the WAIS-IV standardizations further serves to exemplify the issues. RESULTS: A flaw in both South African standardizations is failure to differentiate between African first language individuals with a background of advantaged education vs. those from educationally disadvantaged settings. In addition, the standardizations merge the performance outcomes of distinct racial/ethnic groups that are characterized by differentially advantaged or disadvantaged backgrounds. Consequently, the conversion tables are without relevance for any one of the disparate South African cultural groups. CONCLUSIONS: It is proposed that the traditional notion of a countrywide unitary norming (also known as 'population-based norms') of an IQ test is an unsatisfactory model for valid assessment practices in diverse cultural contexts. The challenge is to develop new solutions incorporating data from finely stratified within-group norms that serve to reveal rather than obscure cross cultural disparity in cognitive test performance. PMID- 27377009 TI - Piecewise linear approximations to model the dynamics of adaptation to osmotic stress by food-borne pathogens. AB - Addition of salt to food is one of the most ancient and most common methods of food preservation. However, little is known of how bacterial cells adapt to such conditions. We propose to use piecewise linear approximations to model the regulatory adaptation of Escherichiacoli to osmotic stress. We apply the method to eight selected genes representing the functions known to be at play during osmotic adaptation. The network is centred on the general stress response factor, sigma S, and also includes a module representing the catabolic repressor CRP cAMP. Glutamate, potassium and supercoiling are combined to represent the intracellular regulatory signal during osmotic stress induced by salt. The output is a module where growth is represented by the concentration of stable RNAs and the transcription of the osmotic gene osmY. The time course of gene expression of transport of osmoprotectant represented by the symporter proP and of the osmY is successfully reproduced by the network. The behaviour of the rpoS mutant predicted by the model is in agreement with experimental data. We discuss the application of the model to food-borne pathogens such as Salmonella; although the genes considered have orthologs, it seems that supercoiling is not regulated in the same way. The model is limited to a few selected genes, but the regulatory interactions are numerous and span different time scales. In addition, they seem to be condition specific: the links that are important during the transition from exponential to stationary phase are not all needed during osmotic stress. This model is one of the first steps towards modelling adaptation to stress in food safety and has scope to be extended to other genes and pathways, other stresses relevant to the food industry, and food-borne pathogens. The method offers a good compromise between systems of ordinary differential equations, which would be unmanageable because of the size of the system and for which insufficient data are available, and the more abstract Boolean methods. PMID- 27377010 TI - Worsening Hypoxemia in the Face of Increasing PEEP: A Case of Large Pulmonary Embolism in the Setting of Intracardiac Shunt. AB - BACKGROUND Patent foramen ovale (PFO) are common, normally resulting in a left-to right shunt or no net shunting. Pulmonary embolism (PE) can cause sustained increased pulmonary vascular resistance (PVR) and right atrial pressure. Increasing positive end-expiratory pressure (PEEP) improves oxygenation at the expense of increasing intrathoracic pressures (ITP). Airway pressure release ventilation (APRV) decreases shunt fraction, improves ventilation/perfusion (V/Q) matching, increases cardiac output, and decreases right atrial pressure by facilitating low airway pressure. CASE REPORT A 40-year-old man presented with dyspnea and hemoptysis. Oxygen saturation (SaO2) 80% on room air with A-a gradient of 633 mmHg. Post-intubation SaO2 dropped to 71% on assist control, FiO2 100%, and PEEP of 5 cmH20. Successive PEEP dropped SaO2 to 60-70% and blood pressure plummeted. APRV was initaiated with improvement in SaO2 to 95% and improvement in blood pressure. Hemiparesis developed and CT head showed infarction. CT pulmonary angiogram found a large pulmonary embolism. Transthoracic echocardiogram detected right-to left intracardiac shunt, with large PFO. CONCLUSIONS There should be suspicion for a PFO when severe hypoxemia paradoxically worsens in response to increasing airway pressures. Concomitant venous and arterial thromboemboli should prompt evaluation for intra-cardiac shunt. Patients with PFO and hypoxemia should be evaluated for causes of sustained right-to-left pressure gradient, such as PE. Management should aim to decrease PVR and optimize V/Q matching by treating the inciting incident (e.g., thrombolytics in PE) and by minimizing ITP. APRV can minimize PVR and maximize V/Q ratios and should be considered in treating patients similar to the one whose case is presented here. PMID- 27377011 TI - Transporter-targeted cholic acid-cytarabine conjugates for improved oral absorption. AB - Cytarabine has a poor oral absorption due to its rapid deamination and poor membrane permeability. Bile acid transporters are highly expressed both in enterocytes and hepatocytes and to increase the oral bioavailability and investigate the potential application of cytarabine for liver cancers, a transporter- recognizing prodrug strategy was applied to design and synthesize four conjugates of cytarabine with cholic acid (CA), chenodeoxycholic acid (CDCA), hyodeoxycholic acid (HDCA) and ursodeoxycholic acid (UDCA). The anticancer activities against HepG2 cells were evaluated by MTT assay and the role of bile acid transporters during cellular transport was investigated in a competitive inhibition experiment. The in vitro and in vivo metabolic stabilities of these conjugates were studied in rat plasma and liver homogenates. Finally, an oral bioavailability study was conducted in rats. All the cholic acid-cytarabine conjugates (40MUM) showed potent antiproliferative activities (up to 70%) against HepG2 cells after incubation for 48h. The addition of bile acids could markedly reduce the antitumor activities of these conjugates. The N(4)-ursodeoxycholic acid conjugate of cytarabine (compound 5) exhibited optimal stability (t1/2=90min) in vitro and a 3.9-fold prolonged half-life of cytarabine in vivo. More importantly, compound 5 increased the oral bioavailability 2-fold compared with cytarabine. The results of the present study suggest that the prodrug strategy based on the bile acid transporters is suitable for improving the oral absorption and the clinical application of cytarabine. PMID- 27377012 TI - Solid state stability and solubility of triethylenetetramine dihydrochloride. AB - The API triethylenetetramine dihydrochloride used as an alternative treatment of Wilson's disease is sensitive to water and it exhibits polymorphism. As this may become an issue for the drug formulation, the physical stability has been studied by differential scanning calorimetry, high-pressure thermal analysis, dynamic vapor sorption, and X-ray diffraction as a function of temperature. In addition, high-pressure liquid chromatography and mass spectrometry have been used to study the purity and chemical stability of the API. A pressure-temperature phase diagram of the pure compound has been constructed and it can be concluded that form II is monotropic in relation to form I, which is the only stable solid. The solubilities of the different solid forms have been determined with the help of a temperature - composition phase diagram. The API is very soluble, at 20 degrees C about 10% of the saturated solution with respect to the dihydrate consists of API and the solubility of the pure form I is twice as high. Moreover, it has been shown that at 20 degrees C, a relative humidity above 40% induces the formation of the dihydrate and at 70% a saturated solution appears. At higher temperatures, the formation of the dihydrate appears at lower relative humidity values. A clear link has been established between the API's chemical stability, its physical stability and the relative humidity in the air. Humidity levels above 40% are detrimental to the quality of the API. PMID- 27377013 TI - The modification of the thrombin generation test for the clinical assessment of dabigatran etexilate efficiency. AB - A new oral anticoagulant, dabigatran etexilate (DE, a prodrug of direct thrombin inhibitor (DTI) dabigatran), has been used clinically to prevent thrombosis. The assessment of dabigatran efficiency is necessary in some clinical cases, such as renal insufficiency, risk of bleeding, and drug interactions. However, a specific thrombin generation test (TGT) that is one of the most informative and sensitive to anticoagulant therapy (calibrated automated thrombinography (SAT)) shows a paradoxical increase of test parameters, such as endogenous thrombin potential (ETP) and peak thrombin, in patients receiving DE. The paradoxical behaviour of ETP and peak thrombin in these patients in the presence of DTIs is mostly caused by a decrease in the activity of thrombin in the alpha2-macroglobulin-thrombin complex that is used as a calibrator in CAT. For a correct estimation of the TGT parameters in patient's plasma containing DTIs we proposed to use our previously described alternative calibration method that is based on the measurement of the fluorescence signal of a well-known concentration of the reaction product (7 amino-4-methylcoumarin). In this study, the validity of such approach was demonstrated in an ex vivo study in patients with knee replacement and two special patients with multiple myeloma, who received DE for thrombosis prophylaxis. PMID- 27377014 TI - MKS1 mutations cause Joubert syndrome with agenesis of the corpus callosum. AB - Joubert syndrome (JS) is a clinically and genetically heterogeneous ciliopathy characterized by episodic hyperpnea and apnea, hypotonia, ataxia, cognitive impairment and ocular motor apraxia. The "molar tooth sign" is pathognomonic of this condition. Mutations in the MKS1 gene are a major cause of Meckel-Gruber syndrome (MKS), the most common form of syndromic neural tube defects, frequently resulting in perinatal lethality. We present the phenotype and genotype of a child with severe JS and agenesis of the corpus callosum (ACC). In our patient, a next generation sequencing (NGS) approach revealed the following two variants of the MKS1 gene: first, a novel missense variant [ c.240G > T (p.Trp80Cys)], which affects a residue that is evolutionarily highly conserved in mammals and ciliates; second, a 29 bp deletion in intron 15 [c.1408-35_1408-7del29], a founder mutation, which in a homozygous state constitutes the major cause of MKS in Finland. We review the MKS1-variants in all of the eleven JS patients reported to date and compare these patients to our case. To our knowledge, this is the first patient with Joubert syndrome and agenesis of the corpus callosum where a potentially causal genotype is provided. PMID- 27377016 TI - Mapping the HLA diversity of the Iberian Peninsula. AB - The polymorphism of HLA genes can be used to reconstruct human peopling history. However, this huge diversity impairs successful matching in stem cell transplantation, a situation which has led to the recruitment of millions of donors worldwide. In parallel to the increase of recruitment, registries are progressively relying on information from population genetics to optimize their donor pools in terms of HLA variability. In this study, the HLA data of 65,000 Spanish bone marrow donors were analyzed together with 60,000 Portuguese individuals to provide a comprehensive HLA genetic map of the Iberian Peninsula. The frequencies of many alleles were shown to vary continuously across the Peninsula, either increasing or decreasing from the Mediterranean coast to the Atlantic domain or from the Strait of Gibraltar to the Pyrenees and Bay of Biscay. Similar patterns were observed for several haplotypes. In addition, within some regions neighboring provinces share a close genetic similarity. These results outline the genetic landscape of the Iberian Peninsula, and confirm that the analysis of the HLA polymorphism may reveal relevant signatures of past demographic events even when data from donor registries are used. This conclusion stimulates future developments of the Spanish registry, presented here for the first time. PMID- 27377017 TI - Unraveling low-resolution structural data of large biomolecules by constructing atomic models with experiment-targeted parallel cascade selection simulations. AB - Various low-resolution experimental techniques have gained more and more popularity in obtaining structural information of large biomolecules. In order to interpret the low-resolution structural data properly, one may need to construct an atomic model of the biomolecule by fitting the data using computer simulations. Here we develop, to our knowledge, a new computational tool for such integrative modeling by taking the advantage of an efficient sampling technique called parallel cascade selection (PaCS) simulation. For given low-resolution structural data, this PaCS-Fit method converts it into a scoring function. After an initial simulation starting from a known structure of the biomolecule, the scoring function is used to pick conformations for next cycle of multiple independent simulations. By this iterative screening-after-sampling strategy, the biomolecule may be driven towards a conformation that fits well with the low resolution data. Our method has been validated using three proteins with small angle X-ray scattering data and two proteins with electron microscopy data. In all benchmark tests, high-quality atomic models, with generally 1-3 A from the target structures, are obtained. Since our tool does not need to add any biasing potential in the simulations to deform the structure, any type of low-resolution data can be implemented conveniently. PMID- 27377018 TI - Care for children and adolescents with diabetes in New Zealand District Health Boards: Is the clinical resourcing ready for the challenge? AB - AIM: Landmark studies, including the Diabetes Control and Complications Trial, have demonstrated the need for intensive management and improvement of glycaemic control in children and adolescents with Type 1 Diabetes (T1DM). Our aim was to determine what clinical resources were present in New Zealand to manage diabetes in children and adolescents and compare this with international recommendations, via the Paediatric Society of New Zealand clinical network. METHOD: All 21 District Health Board (DHB) secondary care sites in New Zealand managing children and adolescents with diabetes were invited to complete a survey about the specialist services they provided in 2012. RESULTS: All of the identified 21 sites (encompassing 20 centres) replied. These centres managed 1,587 children and adolescents with diabetes up to 18 years of age (>95% with T1DM), including 251 (16%) on insulin pumps. Average clinic HbA1c was not available for many centres. Staffing for specialists (general paediatricians or paediatric endocrinologists) was low (median 0.2/100 patients, range 0.1-0.4), but was relatively higher in diabetes nurses (median 0.7/100 patients, range 0.1-1.8). Despite the psychological and social burden of diabetes, the two allied health disciplines (psychology services and social worker) were the hardest to quantify as dedicated resource in these disciplines did not exist in all but three centres. CONCLUSIONS: This survey suggests that the majority of clinical services providing care for children with diabetes in New Zealand are significantly under resourced. PMID- 27377019 TI - Care versus convenience: Examining paracetamol overdose in New Zealand and harm reduction strategies through sale and supply. AB - AIM: To examine statistics on paracetamol overdose in New Zealand and investigate options to reduce paracetamol overdose rates, through supply reduction strategies. METHOD: Data was gathered from the Ministry of Health's National Minimum Dataset and Wellington Hospital Emergency Department attendances. Twenty articles on supply reduction strategies were sourced through article database searches. A survey on paracetamol availability from online pharmacies within New Zealand was conducted by searching for New Zealand online pharmacies through Google. RESULTS: A five-year audit of data (2007-2012) from the Wellington Hospital Emergency Department revealed that paracetamol was the most common medication used for overdose (23%). National data on aminophenol derivatives accounted for 22.4% of poisonings in New Zealand's public hospitals. An online search found that 25 out of 27 online pharmacies sold packets containing 50 grams of paracetamol. However, the literature supported restricting packets to the minimum threshold for an acute exposure (10 g). CONCLUSION: Paracetamol poisoning is the most common form of drug overdose in many developed countries. Tightening restrictions on the quantity of paracetamol sold per packet, in all outlets in New Zealand, may be an effective strategy to reduce overdose rates. This includes online pharmacies where large quantities of paracetamol per packet are available for sale. PMID- 27377020 TI - Differences in acute general surgical admissions between obese or overweight patients compared to normal-sized patients. AB - AIM: Obesity is changing the pattern of modern health and illness. Despite its adverse effect on medical ailments such as diabetes and ischaemic heart disease, its effect on acute general surgical conditions is unknown. This study aims to determine the effect that excess weight and obesity have on acute general surgical conditions. METHODS: A prospective observational cohort study comparing the pattern of acute general surgical admissions in patients with a BMI >25 kg/m(2) to those with a normal BMI from a single tertiary-level hospital. RESULTS: There were 2,676 (21.5%) patients who were overweight or obese (mean BMI 32.4 +/- 6.3 kg/m(2)). These patients were significantly younger than those with normal BMI (48.3 +/- 18.1 years versus 50.5 +/- 22.4 years; p<0.0001). They had a shorter average hospital stay (2.9 +/- 4.2 compared to 3.2 +/- 5.0 days; p=0.14). However, more overweight patients required a visit to theatre (34% compared to 29%; p<0.0001, OR 1.25 (1.14 to 1.37; 95% CI)). Overweight patients were more likely to suffer from biliary conditions (13% compared to 8%; p<0.0001; OR 1.84 (1.60-2.10)) and pancreatitis (6% compared to 4 %; p<0.0001; OR 1.71 (1.42 to 2.06)). In contrast, they were less likely to present with bowel obstruction (4% compared to 6%; p<0.0001, OR 0.63 (0.5 to 0.78)) or GI bleeding (4% compared to 6%; p<0.0001; OR 0.64 (0.51 to 0.79)). CONCLUSIONS: Overweight or obese patients present at a younger age and with a higher predominance of gallstone related diseases. PMID- 27377015 TI - Role of Inflammation in Suicide: From Mechanisms to Treatment. AB - Suicidal behavior is complex and manifests because of a confluence of diverse factors. One such factor involves dysregulation of the immune system, which has been linked to the pathophysiology of suicidal behavior. This review will provide a brief description of suicidality and discuss the contribution of upstream and downstream factors in the etiology of suicidal behavior, within the contextual framework of inflammation. The contribution of inflammatory conditions such as traumatic brain injury, autoimmune disorders, and infections to neuropsychiatric symptoms and suicidality is only beginning to be explored. We will summarize studies of inflammation in the etiology of suicide, and provide a neurobiological basis for different mechanisms by which inflammation might contribute to the pathophysiology. Finally, we will review treatments that affect upstream and downstream pathways related to inflammation in suicidality. PMID- 27377021 TI - Risk management and clinical practice. PMID- 27377022 TI - The case for a systematic policy approach to free primary health care for vulnerable groups in New Zealand. AB - Unmet health care needs and health inequities are prevalent in New Zealand. Throughout New Zealand's history, the power dynamic between general practitioners, as a professional group, and the government has contributed to policies directed at primary-care access barriers not being fully realised. This has given 'third sector' (non-government, non-profit) clinics a continuing role in delivering primary care services to vulnerable populations. The viability of free clinics, 18 of which were identified in our survey, is threatened by their funding and staffing structures. We contend that general practitioners have a stake in reducing health inequities and that there is a strong case for a more systematic policy approach to primary health care provision for vulnerable populations in New Zealand. PMID- 27377023 TI - Reducing perioperative harm in New Zealand: the WHO Surgical Safety Checklist, briefings and debriefings, and venous thrombembolism prophylaxis. AB - New Zealand appears to have a relatively high rate of perioperative adverse events. The Health Quality & Safety Commission's Safe Surgery NZ programme was introduced to address the rates of perioperative harm in New Zealand by promoting proper and effective use of the World Health Organization (WHO) Surgical Safety Checklist, and by encouraging use of operating room (OR) team briefings and debriefings. Venous thromboembolism prophylaxis is a key part of the checklist as deployed in New Zealand ORs, but it remains underused or variably used as well. Communication and teamwork are critical to improving patient safety and efficiency in the OR, and these interventions have demonstrated effectiveness in building and melding effective teams. PMID- 27377024 TI - Protrusion of nasal floor. PMID- 27377025 TI - Massive localised lymphoedema: a new benign entity in the morbidly obese patient. PMID- 27377026 TI - Bilateral vertebral artery dissection in a patient with Turner Syndrome following manipulation of the cervical spine. PMID- 27377027 TI - RNA-Seq revealed the impairment of immune defence of tilapia against the infection of Streptococcus agalactiae with simulated climate warming. AB - Global warming is one of the causes of disease outbreaks in fishes. Understanding its mechanisms is critical in aquaculture and fisheries. We used tilapia to study the effects of a high temperature on the infection of a bacterial pathogen Streptococcus agalactiae using RNA-Seq. We found that the dissolved oxygen level in water at 32 degrees C is lower than at 22 degrees C, and tilapia infected with the pathogen died more rapidly at 32 degrees C. The gene expression profiles showed significant differences in fish raised under different conditions. We identified 126 and 576 differentially expressed genes (DEGs) at 4 and 24 h post infection at 22 degrees C, respectively, whereas at 32 degrees C, the data were 312 and 1670, respectively. Almost all responding pathways at 22 degrees C were involved in the immune responses, whereas at 32 degrees C, the enriched pathways were not only involved in immune responses but also involved in oxygen and energy metabolisms. We identified significant signals of immunosuppression of immune responses at 32 degrees C. In addition, many of the enriched transcription factors and DEGs under positive selection were involved in immune responses, oxygen and/or energy metabolisms. Our results suggest that global warming could reduce the oxygen level in water and impair the defence of tilapia against bacterial infection. PMID- 27377028 TI - Immunity enhancement with administration of Gracilaria corticata and Saccharomyces cerevisiae compared to gamma irradiation in expose to WSSV in shrimp, in juvenile Litopenaeus vannamei: A comparative study. AB - This paper investigates the efficacy of Gracilaria corticata, Saccharomyces cerevisiae and gamma irradiation WSSV as immunostimulants to white shrimp Litopenaeus vannamei. Seven hundred and twenty healthy shrimp SPF L. vannamei subadult with average weight of 10 +/- 1.02 g were collected and divided into 8 groups. The first group (T1) was fed with commercial pellet, the second group (T2) fed with S. cerevisiae (2 g/kg), the third group (T3) fed with G. corticata powder mixed with shrimp feed (2 g/kg) and, finally, the fourth group (T4) was fed with commercial pellet and injected intramuscularly gamma irradiant WSSV (1 MUl/gbw) for 10 days. The shrimps were then injected with WSSV and maintained for 25 days. The positive control group for each treatment was maintained in the same manner but without injection with WSSV. Moreover, survival rate and immune parameters such as total hemocyte count (THC), total protein plasma (TPP), superoxide dismutase (SOD) activity, peroxidase (POD) activity and phenoloxidase activity (PO) were determined. Results indicated that the survival rates for groups T4, T3 T2 and T1 were 57.05 +/- 3.52%, 22.5 +/- 0.5%, 15 +/- 1.05% and 00.0 +/- 0%, respectively. Ultimately, at the end of the study the shrimp group T4 showed higher hematological data: THC, TPP, SOD, POD and PO. The study concluded that gamma irradiant WSSV is effective immunostimulants in shrimp L. vannamei and the immunity has better performances than those of the G. corticata and S. cerevisiae. PMID- 27377029 TI - Analysis of digital gene expression profiling in hemocytes of white shrimp Litopenaeus vannamei under nitrite stress. AB - Accumulation of nitrite in water is highly toxic to aquatic animals. To understand immune responses in shrimp under such environmental stress, a digital gene expression (DGE) technology was applied to detect the gene expression profile of the Litopenaeus vannamei hemocytes in response to nitrite for 48 h. A total of 1922 differently expressed unigenes were generated. Of these transcripts, 1269 and 653 genes were up- or down-regulated respectively. Functional categorization and pathways of the differentially expressed genes revealed that immune defense, xenobiotics biodegradation and metabolism, amino acid and nucleobase metabolic process, apoptosis were the differentially regulated processes occurring during nitrite stress. We selected 19 differential expression transcripts (DETs) to validate the sequencing results by real time quantitative PCR (qPCR). The Pearson's correlation coefficient (R) of the 19 DETs was 0.843, which confirmed the consistency and accuracy between these two approaches. Subsequently, we screened 10 genes to examine the changes in the time course of gene expression in more detail. The results indicated that expressions of ATP-binding cassette transporter (ABC transporter), caspase10, QM protein, C type lectin 4 (CTL4), protein disulfide isomerase (PDI), serine protease inhibitor 8 (SPI8), transglutaminase (TGase), chitinase1, inhibitors of apoptosis proteins (IAP) and cytochrome P450 enzyme (CYP450) were induced to participate in the anti-stress defense against nitrite. These results will provide a reference for follow-up study of molecular toxicology and valuable gene information for better understanding of immune response in L. vannamei under environmental stress. PMID- 27377030 TI - Determinants of self-efficacy and quality of life in patients with temporary enterostomy: a cross-sectional survey. AB - AIMS AND OBJECTIVES: To identify determinants of self-efficacy and quality of life in patients with temporary enterostomy. BACKGROUND: Anterior resection with temporary enterostomy is the preferred treatment for patients with rectal cancer, which may impair patients' quality of life. So far, most studies have focused on quality of life in patients with permanent enterostomy, but few studies have looked at that in those with temporary enterostomy. Self-efficacy may determine quality of life in these patients, but few studies have identified determinants of self-efficacy and quality of life. DESIGN: Multicentre, cross-sectional survey and regression analysis to identify determinants of self-efficacy and quality of life. METHODS: A convenience sample of patients undergoing temporary enterostomy at five hospitals in Guangdong Province (China) were surveyed at least four weeks after stoma surgery using validated Chinese versions of internationally recognised questionnaires, including a Stoma Self-Efficacy Scale and the City of Hope Quality of Life-Ostomy Questionnaire. Backward multiple regression analysis was performed to identify whether quality of life was determined by self-efficacy and other clinico-demographic characteristics. RESULTS: Of the 180 questionnaires distributed, 149 (82.8%) were returned, and 135 (75%) were used in the final analysis. Mean global quality of life was 5.40 +/- 1.58, and mean global self efficacy was 79.59 +/- 20.21. Significant determinants of self-efficacy and quality of life were identified (beta = 0.62, p < 0.01). Quality of life was determined by type of enterostomy (beta = 0.18, p = 0.01) and payment method (beta = 0.14, p = 0.03). CONCLUSIONS: Quality of life may be determined by self efficacy, type of enterostomy and payment method, after temporary enterostomy. RELEVANCE TO CLINICAL PRACTICE: Promoting stoma-related self-efficacy in patients with temporary enterostomy may improve their quality of life. Healthcare providers should focus on quality of life in those either with temporary loop ileostomy or entirely self-funded for medicine. PMID- 27377031 TI - Glycogen synthase kinase 3beta suppresses polyglutamine aggregation by inhibiting Vaccinia-related kinase 2 activity. AB - Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormal expansion of polyglutamine repeats in the N-terminal of huntingtin. The amount of aggregate-prone protein is controlled by various mechanisms, including molecular chaperones. Vaccinia-related kinase 2 (VRK2) is known to negatively regulate chaperonin TRiC, and VRK2-facilitated degradation of TRiC increases polyQ protein aggregation, which is involved in HD. We found that VRK2 activity was negatively controlled by glycogen synthase kinase 3beta (GSK3beta). GSK3beta directly bound to VRK2 and inhibited the catalytic activity of VRK2 in a kinase activity independent manner. Furthermore, GSK3beta increased the stability of TRiC and decreased the formation of HttQ103-GFP aggregates by inhibiting VRK2. These results indicate that GSK3beta signaling may be a regulatory mechanism of HD progression and suggest targets for further therapeutic trials for HD. PMID- 27377032 TI - Three-dimensional posture changes of the vocal fold from paired intrinsic laryngeal muscles. AB - OBJECTIVES/HYPOTHESIS: Although the geometry of the vocal fold medial surface affects voice quality and is critical in the treatment of glottic insufficiency, the prephonatory shape of the vocal fold medial surface is not well understood. In this study, we activated intrinsic laryngeal muscles individually and in combinations, and recorded the temporal sequence and precise three-dimensional configurational changes of the vocal fold medial surface. STUDY DESIGN: In vivo canine hemilarynx model. METHODS: A hemilaryngectomy was performed in an in vivo canine model and ink was used to mark the medial surface of the in situ vocal fold in a grid-like fashion. The thyroarytenoid (TA), lateral cricoarytenoid (LCA), cricothyroid (CT), and posterior cricoarytenoid (PCA) muscles were stimulated individually and in combinations. A right-angle prism whose hypotenuse formed the glottal midline provided two distinct views of the medial surface for a high-speed digital camera. Image-processing package DaVis (LaVision Inc., Goettingen, Germany) allowed time series cross-correlation analysis for three dimensional deformation calculations of the vocal fold medial surface. RESULTS: Combined TA and LCA activation yields an evenly adducted rectangular glottal surface. Addition of thyroarytenoid to cricoarytenoid adducts the vocal fold from inferior to superior in a graded fashion allowing formation of a divergent glottis. Posterior cricoarytenoid has a bimodal relationship with thyroarytenoid favoring abduction. Cricothyroid and lateral cricoarytenoid yield unique glottal postures necessary but likely not conducive for efficient phonation. CONCLUSIONS: Understanding the three-dimensional geometry of the vocal fold medial surface will help us better understand the cause-effect relationship between laryngeal physiology and phonation. LEVEL OF EVIDENCE: NA Laryngoscope, 127:656-664, 2017. PMID- 27377033 TI - Design of functionalized gold nanoparticle probes for computed tomography imaging. AB - The development of new molecules able to efficiently act as long-circulating computed tomography (CT) contrast agents is one of the most crucial topics in the biomedical field. In the last years, the chance to manipulate materials at the nano-size level gave new boost to this research, with the specific aim to design innovative nanoprobes. Gold nanoparticles (AuNPs) have showed unique X-rays attenuation properties which, combined with their easy surface functionalization, makes them ideal candidates for the next generation of contrast agents. In this paper, we present a rational and facile approach to synthesize engineered and water-stable AuNPs, achieving concentrated colloidal solution with high Hounsfield Units (HU). An accurate control of reagents ratio allowed us to design AuNPs with different shapes, from symmetrical to anisotropic morphology, in a convenient 'one-pot' fashion. Their activity as efficient and reliable CT contrast agents has been evaluated and compared. Moreover, glucosamine functionalized gold nanoparticles have been developed ([Au] = 31.20 mg/mL; HU = 2453), in order to obtain a CT contrast agent able to combine spatial resolution with metabolic information. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27377034 TI - Predictive Model for the Meniscus-Guided Coating of High-Quality Organic Single Crystalline Thin Films. AB - A model that describes solvent evaporation dynamics in meniscus-guided coating techniques is developed. In combination with a single fitting parameter, it is shown that this formula can accurately predict a processing window for various coating conditions. Organic thin-film transistors (OTFTs), fabricated by a zone casting setup, indeed show the best performance at the predicted coating speeds with mobilities reaching 7 cm2 V-1 s-1 . PMID- 27377035 TI - Rational Design of Biomolecular Templates for Synthesizing Multifunctional Noble Metal Nanoclusters toward Personalized Theranostic Applications. AB - Biomolecule-templated or biotemplated metal nanoclusters (NCs) are ultrasmall (<2 nm) metal (Au, Ag) particles stabilized by a certain type of biomolecular template (e.g., peptides, proteins, and DNA). Due to their unique physiochemical properties, biotemplated metal NCs have been widely used in sensing, imaging, delivery and therapy. The overwhelming applications in these individual areas imply the great promise of harnessing biotemplated metal NCs in more advanced biomedical aspects such as theranostics. Although applications of biotemplated metal NCs as theranostic agents are trending, the rational design of biomolecular templates suitable for the synthesis of multifunctional metal NCs for theranostics is comparatively underexplored. This progress report first identifies the essential attributes of biotemplated metal NCs for theranostics by reviewing the state-of-art applications in each of the four modalities of theranostics, namely sensing, imaging, delivery and therapy. To achieve high efficacy in these modalities, we elucidate the design principles underlying the use of biomolecules (proteins, peptides and nucleic acids) to control the NC size, emission color and surface chemistries for post-functionalization of therapeutic moieties. We then propose a unified strategy to engineer biomolecular templates that combine all these modalities to produce multifunctional biotemplated metal NCs that can serve as the next-generation personalized theranostic agents. PMID- 27377036 TI - COMPUTED TOMOGRAPHY OF TOOTH RESORPTION IN CATS. AB - Tooth resorption is the most common dental disease in cats and can be a source of oral pain. The current clinical gold standard for diagnosis includes a combination of oral exam and dental radiography, however early lesions are not always detected. Computed tomography (CT) of the skull, including the dental arches, is a commonly performed diagnostic procedure, however the appearance of tooth resorption on CT and the diagnostic ability of CT to detect tooth resorption have not been evaluated. The purpose of this prospective, descriptive, diagnostic accuracy study was to characterize the CT appearance of tooth resorption in a sample of affected cats and to evaluate the sensitivity and specificity of CT for tooth resorption compared to the clinical gold standard of oral exam and intraoral dental radiography. Twenty-eight cat cadaver specimens were recruited for inclusion. Each specimen was evaluated using oral exam, intraoral dental radiography, and computed tomography (four different slice thicknesses). Each tooth was evaluated for the presence or absence of tooth resorption. Teeth with lesions and a subset of normal teeth were evaluated with histopathology. On CT, tooth resorption appeared as irregularly marginated hypoattenuating defects in the mineral attenuating tooth components, most commonly involving the root or cementoenamel junction. Sensitivity for CT detection of tooth resorption was fair to poor (42.2-57.7%) and specificity was good to excellent (92.8-96.3%). Findings from this study indicated that CT has high specificity but low sensitivity for detection of tooth resorption in cats. PMID- 27377037 TI - Synthesis of photoactivatable azido-acyl caged oxazine fluorophores for live-cell imaging. AB - We report the design and synthesis of a photoactivatable azido-acyl oxazine fluorophore. Photoactivation is achieved cleanly and rapidly with UV light, producing a single fluorescent oxazine photoproduct. We demonstrate the utility of azido-acyl caged oxazines for protein specific labeling in living mammalian cells using the TMP-tag technology. PMID- 27377038 TI - Copper induced hollow carbon nanospheres by arc discharge method: controlled synthesis and formation mechanism. AB - Hollow carbon nanospheres with controlled morphologies were synthesized via the copper-carbon direct current arc discharge method by alternating the concentrations of methane in the reactant gas mixture. A self-healing process to keep the structural integrity of encapsulated graphitic shells was evolved gradually by adding methane gas from 0% to 20%. The outer part of the coated layers expanded and hollow nanospheres grew to be large fluffy ones with high methane concentrations from 30% to 50%. A self-repairing function by the reattachment of broken graphitic layers initiated from near-electrode space to distance was also distinctly exhibited. By comparing several comparable metals (e.g. copper, silver, gold, zinc, iron and nickel)-carbon arc discharge products, a catalytic carbon-encapsulation mechanism combined with a core-escaping process has been proposed. Specifically, on the basis of the experimental results, copper could be applied as a unique model for both the catalysis of graphitic encapsulation and as an adequate template for the formation of hollow nanostructures. PMID- 27377039 TI - Diagnostic characteristics of lower limb venous compression ultrasonography in suspected pulmonary embolism: a meta-analysis. AB - Essentials Lower limb ultrasonography (CUS) could be useful in suspected pulmonary embolism (PE). We performed a metaanalysis on the diagnostic characteristics of CUS in suspected PE. With a sensitivity of 41%, proximal CUS would be positive in one of every 7.3 patients. Complete CUS has a higher sensitivity but specificity for PE is too low to use it in suspected PE. SUMMARY: Background Diagnosis of pulmonary embolism (PE) is commonly based on D-dimer measurement and computed tomography (CT) angiography. Lower limb vein compression ultrasonography (CUS) for diagnosing deep vein thrombosis may be of interest in patients with suspected PE. Objectives We aimed to summarize the data on the diagnostic characteristics of CUS in suspected PE patients. Patients/Methods We conducted a literature review by using PUBMED and EMBASE and included 15 prospective studies in which CUS was performed in consecutive patients with suspected PE. Results Of the 6991 included patients, 2001 (30%) had pulmonary embolism. Eight of the 15 studies included only outpatients, two included hospitalized patients and five involved both in- and outpatients. In 13 studies, only proximal CUS was performed. Two studies analyzed the added value of distal CUS including the calf veins (whole-leg CUS). Pooled estimate of proximal CUS sensitivity was 41% (95% confidence interval [CI], 36-46%) with strong heterogeneity (I square, 79%). Specificity of proximal CUS was 96% (95% CI, 94 98%). The overall positive likelihood ratio for proximal CUS was 11.9 (95% CI, 7.1-19.8), whereas the overall negative likelihood ratio was 0.6 (95% CI, 0.5 0.7). The sensitivity of whole-leg CUS was 79% (95% CI, 24-98%) and specificity was 84% (95% CI, 76-90%). Conclusions Proximal CUS has low sensitivity and cannot be used to rule out PE. Nevertheless, its high specificity allows confirming PE, which may be useful in patients with contraindications to CT angiography. Whole leg CUS has a higher sensitivity but low specificity for PE and can therefore not be recommended. PMID- 27377040 TI - Pharmacokinetic parameters of three active ingredients hederacoside C, hederacoside D, and alpha-hederin in Hedera helix in rats. AB - In Hedera helix hederacoside C, hederacoside D, and alpha-hederin are three major bioactive saponins and play pivotal roles in the overall biological activity. In this study, a specific and sensitive ultra-high performance liquid chromatography with tandem mass spectrometry method has been developed and validated for the quantification of three major bioactive saponins in rat plasma. Chromatographic separation was performed on a reversed-phase Thermo Hypersil GOLD C18 column (2.1 mm * 50 mm, 1.9 MUm) using a gradient mobile phase system of acetonitrile-water containing 0.1% formic acid. The assay was successfully applied to study the pharmacokinetic behavior of the three analytes in rats after oral and intravenous administration of a mixture of saponins (hederacoside C, hederacoside D, and alpha-hederin). Further research was performed to compare the pharmacokinetic behavior of the three analytes after the oral administration of a mixture of saponins and an extract of saponins from Hedera helix, and results showed that double peaks were evident on concentration-time profile for each of the three saponins. The difference in the pharmacokinetic characteristics of three saponins between a mixture of saponins and an extract of saponins from Hedera helix was found in rat, which would be beneficial for the preclinical research and clinical use of Hedera helix. PMID- 27377041 TI - Effect of early vs. late tracheostomy on clinical outcomes in critically ill pediatric patients. AB - BACKGROUND: Few studies investigated the optimal timing for tracheostomy and its influence on the clinical outcomes in critically ill pediatric patients. This study evaluated the differences in clinical outcomes between early and late tracheostomy in pediatric intensive care unit (ICU) patients. METHODS: We assessed 111 pediatric patients. Patients who underwent a tracheostomy within 14 days of mechanical ventilation (MV) were assigned to the early tracheostomy group, whereas those who underwent tracheostomy after 14 days of MV were included in the late tracheostomy group. Clinical outcomes, including mortality, duration of MV, length of ICU and hospital stays, and incidence of ventilator-associated pneumonia (VAP) were compared between the groups. RESULTS: Of the 111 pediatric patients, 61 and 50 were included in the early and late tracheostomy groups, respectively. Total MV duration and the length of ICU and hospital stay were significantly longer in the late tracheostomy group than in the early tracheostomy group (all P < 0.01). The VAP rate per 1000 ventilator days before tracheostomy was 2.6 and 3.8 in the early and late tracheostomy groups, respectively. There were no significant differences in mortality rate between the groups. No severe complications were associated with tracheostomy itself. CONCLUSIONS: Tracheostomy performed within 14 days after the initiation of MV was associated with reduced duration of MV and length of ICU and hospital stay. Although there was no effect on mortality rate, children may benefit from early tracheostomy without severe complications. PMID- 27377042 TI - Local Inhibition of Complement Improves Mesenchymal Stem Cell Viability and Function After Administration. AB - The results of recent clinical trials using mesenchymal stem cells (MSCs) have been unsatisfactory, indicating that current MSC-based therapies need to be improved. We and others have previously demonstrated that MSCs activate complement by unknown mechanisms after infusion, leading to damaged MSCs. In the study reported here, we found that incorporation of N-glycolylneuraminic acid onto MSCs during in vitro culture was a factor in the activation of complement by MSCs. In addition, we developed a way to "paint" heparin onto MSCs. This novel method improved the viability of MSCs and enhanced their function after infusion by directly inhibiting complement and by recruiting factor H, another potent complement inhibitor in serum, onto the surface of the MSCs. These data suggest that cell-surface engineering of MSCs with heparin to locally inhibit complement activation on MSCs might be a straightforward and effective method for improving the outcome of current MSC-based therapies. PMID- 27377045 TI - A Case of Angioinvasive Cutaneous Anaplastic Large Cell Lymphoma Completely Regressed After Low-dose Systemic Methotrexate. PMID- 27377043 TI - Enhancing Antitumor Immune Responses by Optimized Combinations of Cell penetrating Peptide-based Vaccines and Adjuvants. AB - Cell penetrating peptides (CPPs) from the protein ZEBRA are promising candidates to exploit in therapeutic cancer vaccines, since they can transport antigenic cargos into dendritic cells and induce tumor-specific T cells. Employing CPPs for a given cancer indication will require engineering to include relevant tumor associated epitopes, administration with an appropriate adjuvant, and testing for antitumor immunity. We assessed the importance of structural characteristics, efficiency of in vitro transduction of target cells, and choice of adjuvant in inducing the two key elements in antitumor immunity, CD4 and CD8 T cells, as well as control of tumor growth in vivo. Structural characteristics associated with CPP function varied according to CPP truncations and cargo epitope composition, and correlated with in vitro transduction efficiency. However, subsequent in vivo capacity to induce CD4 and CD8 T cells was not always predicted by in vitro results. We determined that the critical parameter for in vivo efficacy using aggressive mouse tumor models was the choice of adjuvant. Optimal pairing of a particular ZEBRA-CPP sequence and antigenic cargo together with adjuvant induced potent antitumor immunity. Our results highlight the irreplaceable role of in vivo testing of novel vaccine constructs together with adjuvants to select combinations for further development. PMID- 27377046 TI - Activation of Platinum(IV) Prodrugs By Motexafin Gadolinium as a Redox Mediator. AB - Water-soluble platinum(IV) prodrugs, which proved kinetically stable to reduction in the presence of physiological concentration of ascorbate, were quickly reduced to their active form, oxaliplatin, when co-incubated with a macrocycle metallotexaphyrin (i.e., Motexafin Gadolinium (MGd)). The reduction of Pt(IV) to Pt(II) promoted by MGd occurs in cell culture as well, leading to an increase in the antiproliferative activity of the Pt(IV) species in question. The mediated effect is proportional to the concentration of MGd and gives rise to an enhancement when the prodrug is relatively hydrophilic. MGd is known to localize/accumulate preferentially in tumor tissues. Thus, the present "activation by reduction" approach may allow for the cancer-selective enhancement in the cytotoxicity of Pt(IV) prodrugs. PMID- 27377047 TI - Synthesis, structure, magnetic and biological activity studies of bis-hydrazone derived Cu(ii) and Co(ii) coordination compounds. AB - Four coordination compounds of formulae [Cu(II)2(H2L(1))(HL(1))](ClO4)3.H2O (1), [Cu(II)2(H2L(2))(CH3OH)2](ClO4)2.2CH3OH (2), [Co(II)2(H2L(1))2](ClO4)4 (3) and [Co(II)2(H2L(2))2].2H2O (4) were synthesized via self-assembly of succinohydrazone derived ligands (H2L(1) = N',N'-4-bis(2 pyridyl)succinohydrazide, H4L(2) = N',N'-4-bis(2 hydroxybenzylidene)succinohydrazide) and Cu(2+) and Co(2+) ions, respectively. The compounds were characterized by crystal structure determination, magnetic measurements and biological activities. Compounds 1, 3 and 4 have discrete double helicate structures, whereas compound 2 is a one-dimensional chain. Magnetic studies show antiferromagnetic exchange interactions in 2 with a J value of -67.1 cm(-1) and antiferromagnetic spin-canting in compound 3 originates through supramolecular H-bonding. For compound 3, a clear bifurcation was observed in zero field cooled (ZFC) and field cooled (FC) measurement at a temperature of 3.5 K and field of 0.1 T, implying long range magnetic ordering below this temperature. Interestingly, all of compounds 1-4 show significant changes in their absorption (hypo- and hyperchromism) in the presence of SS-DNA, inferring interaction between the compounds and DNA. In addition, compounds 1-4 significantly exhibited nuclease activities on both RNA and pUC19 plasmid DNA. Moreover, the nuclease activity was further enhanced in the presence of oxidant (H2O2) and suggests the possible role of reactive oxygen species in DNA nicking ability of compounds 1-4. Furthermore, compounds 1, 2 and 4 exhibited significant cytotoxicity against mammalian cancer cell lines (HeLa, A549 and MDAMB-231). In addition, our results from Annexin/PI staining and DNA fragmentation assays revealed that these compounds are capable of inducing apoptosis and have potential to act as anticancer drugs. PMID- 27377048 TI - Finite-size scaling in silver nanowire films: design considerations for practical devices. AB - We report the first application of finite-size scaling theory to nanostructured percolating networks, using silver nanowire (AgNW) films as a model system for experiment and simulation. AgNWs have been shown to be a prime candidate for replacing Indium Tin Oxide (ITO) in applications such as capacitive touch sensing. While their performance as large area films is well-studied, the production of working devices involves patterning of the films to produce isolated electrode structures, which exhibit finite-size scaling when these features are sufficiently small. We demonstrate a generalised method for understanding this behaviour in practical rod percolation systems, such as AgNW films, and study the effect of systematic variation of the length distribution of the percolating material. We derive a design rule for the minimum viable feature size in a device pattern, relating it to parameters which can be derived from a transmittance-sheet resistance data series for the material in question. This understanding has direct implications for the industrial adoption of silver nanowire electrodes in applications where small features are required including single-layer capacitive touch sensors, LCD and OLED display panels. PMID- 27377044 TI - Viral and Synthetic RNA Vector Technologies and Applications. AB - Use of RNA is an increasingly popular method to transiently deliver genetic information for cell manipulation in basic research and clinical therapy. In these settings, viral and nonviral RNA platforms are employed for delivery of small interfering RNA and protein-coding mRNA. Technological advances allowing RNA modification for increased stability, improved translation and reduced immunogenicity have led to increased use of nonviral synthetic RNA, which is delivered in naked form or upon formulation. Alternatively, highly efficient viral entry pathways are exploited to transfer genes of interest as RNA incorporated into viral particles. Current viral RNA transfer technologies are derived from Retroviruses, nonsegmented negative-strand RNA viruses or positive stranded Alpha- and Flaviviruses. In retroviral particles, the genes of interest can either be incorporated directly into the viral RNA genome or as nonviral RNA. Nonsegmented negative-strand virus-, Alpha- and Flavivirus-derived vectors support prolonged expression windows through replication of viral RNA encoding genes of interest. Mixed technologies combining viral and nonviral components are also available. RNA transfer is ideal for all settings that do not require permanent transgene expression and excludes potentially detrimental DNA integration into the target cell genome. Thus, RNA-based technologies are successfully applied for reprogramming, transdifferentiation, gene editing, vaccination, tumor therapy, and gene therapy. PMID- 27377049 TI - Fluorescent-based evaluation of chaperone-mediated autophagy and microautophagy activities in cultured cells. AB - The autophagy-lysosome protein degradation is further classified into macroautophagy (MA), microautophagy (mA), and chaperone-mediated autophagy (CMA). While MA is involved in various functions and disease pathogenesis, little is known about CMA and mA because of the absence of easy methods to assess their activities. We have recently established a method to assess CMA activity using glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a CMA substrate, and HaloTag (HT) system. Another group has recently identified a mammalian mA pathway, in which substrates are delivered to late endosomes in an heat shock cognate protein (Hsc)70-dependent manner. Because Hsc70 is also involved in CMA, our method would detect both CMA and mA activities. In this study, we attempted to assess CMA and mA activities separately through the siRNA-mediated knockdown of CMA- and mA related proteins. Knockdown of LAMP2A, a CMA-related protein, and TSG101, an mA related protein, significantly but only partially decreased the punctate accumulation of GAPDH-HT in AD293 cells and primary cultured rat cortical neurons. Compounds that activate CMA significantly increased GAPDH-HT puncta in TSG101-knockdown cells, but not in LAMP2A-knockdown cells, suggesting that punctate accumulation of GAPDH-HT under LAMP2A- and TSG101-knockdown represents mA and CMA activities, respectively. We succeeded in establishing the method to separately evaluate CMA and mA activities by fluorescence observation. PMID- 27377050 TI - Radiation Recall Dermatitis Secondary to Dactinomycin. AB - Radiation recall dermatitis (RRD) is an uncommon reaction typically triggered by the use of chemotherapeutic agents in the months after treatment with radiation therapy. It usually presents as dermatitis in the irradiated field with prominent intertriginous involvement, and because internal involvement occurs in up to one third of cases, early recognition is important. RRD has rarely been reported in the pediatric literature. We report the case of a 15-month-old boy with RRD to dactinomycin. PMID- 27377051 TI - GSK-3beta inhibitors reverse cocaine-induced synaptic transmission dysfunction in the nucleus accumbens. AB - Nucleus accumbens receives glutamatergic projection from the prefrontal cortex (PFC) and dopaminergic input from the Ventral tegmental area (VTA). Recent studies have suggested a critical role for serine/threonine kinase glycogen synthase kinase 3beta (GSK3beta) in cocaine-induced hyperactivity; however, the effect of GSK3beta on the modulation of glutamatergic and dopaminergic afferents is unclear. In this study, we found that the GSK3 inhibitors, LiCl (100 mg/kg, i.p.) or SB216763 (2.5 mg/kg, i.p.), blocked the cocaine-induced hyperlocomotor activity in rats. By employing single-unit recordings in vivo, we found that pretreatment with either SB216763 or LiCl for 15 min reversed the cocaine inhibited firing frequency of medium spiny neuron (MSN) in the nucleus accumbens (NAc). Preperfusion of SB216763 (5 MUM) ameliorated the inhibitory effect of cocaine on both the alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (up to 99 +/- 6.8% inhibition) and N-methyl-D-aspartic acid receptor (NMDAR)-mediate EPSC (up to 73 +/- 9.7% inhibition) in the NAc in brain slices. The effect of cocaine on AMPA and NMDA receptor-mediate excitatory postsynaptic current (EPSC) were mimicked by the D1 -like receptor agonist SKF 38393 and blocked by the D1 -like receptor antagonist SCH 23390, whereas D2 -like receptor agonist or antagonist failed to mimic or to block the action of cocaine. Preperfusion of SB216763 for 5 min also ameliorated the inhibitory effect of SKF38393 on both AMPA and NMDA receptor-mediated components of EPSC, indicate the effect of SB216763 on cocaine was via the D1 -like receptor. Moreover, cocaine inhibited the presynaptic release of glutamate in the NAc, and SB216763 reversed this effect. In conclusion, D1 receptor-GSK3beta pathway, which mediates glutamatergic transmission in the NAc core through a presynaptic mechanism, plays an important role in acute cocaine-induced hyperlocomotion. PMID- 27377052 TI - A compact short-capillary based high-speed capillary electrophoresis bioanalyzer. AB - Here, a compact high-speed CE bioanalyzer based on a short capillary has been developed. Multiple modules of picoliter scale sample injection, high-speed CE separation, sample changing, LIF detection, as well as a custom designed tablet computer for data processing, instrument controlling, and result displaying were integrated in the bioanalyzer with a total size of 23 * 17 * 19 cm (length * width * height). The high-speed CE bioanalyzer is capable of performing automated sample injection and separation for multiple samples and has been successfully applied in fast separations of amino acids, chiral amino acids, proteins and DNA fragments. For instance, baseline separation of six FITC-labeled amino acids and ultrahigh-speed separation of three amino acids could be achieved within 7 and 1 s, respectively. The separation speed and efficiency of the optimized high-speed CE system are comparable to or even better than those reported in microchip-based CE systems. We believe this bioanalyzer could provide an advanced platform for fundamental research in bioscience and clinical diagnosis, as well as in quality control for drugs, foods, and feeds. PMID- 27377053 TI - The phenotype and clinical course of Japanese Fanconi Anaemia infants is influenced by patient, but not maternal ALDH2 genotype. AB - Studies using Fanconi anaemia (FA) mutant mouse models suggested that the combination of a defective FA pathway and aldehyde dehydrogenase-2 (ALDH2) dysfunction could provoke bone marrow failure, leukaemia and developmental defects, and that both maternal and fetal aldehyde detoxification are crucial to protect the developing embryo from DNA damage. We studied the ALDH2 genotypes of 35 Japanese FA patients and their mothers. We found that a normal maternal ALDH2 allele was not essential for fetal development of ALDH2-deficient patients, and none of the post-natal clinical parameters were clearly affected by the maternal ALDH2 genotype in these patients. PMID- 27377054 TI - Robust anti-obesity and metabolic effects of a dual GLP-1/glucagon receptor peptide agonist in rodents and non-human primates. AB - AIMS: To characterize the pharmacology of MEDI0382, a peptide dual agonist of glucagon-like peptide-1 (GLP-1) and glucagon receptors. MATERIALS AND METHODS: MEDI0382 was evaluated in vitro for its ability to stimulate cAMP accumulation in cell lines expressing transfected recombinant or endogenous GLP-1 or glucagon receptors, to potentiate glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cell lines and stimulate hepatic glucose output (HGO) by primary hepatocytes. The ability of MEDI0382 to reduce body weight and improve energy balance (i.e. food intake and energy expenditure), as well as control blood glucose, was evaluated in mouse models of obesity and healthy cynomolgus monkeys following single and repeated daily subcutaneous administration for up to 2 months. RESULTS: MEDI0382 potently activated rodent, cynomolgus and human GLP-1 and glucagon receptors and exhibited a fivefold bias for activation of GLP-1 receptor versus the glucagon receptor. MEDI0382 produced superior weight loss and comparable glucose lowering to the GLP-1 peptide analogue liraglutide when administered daily at comparable doses in DIO mice. The additional fat mass reduction elicited by MEDI0382 probably results from a glucagon receptor-mediated increase in energy expenditure, whereas food intake suppression results from activation of the GLP-1 receptor. Notably, the significant weight loss elicited by MEDI0382 in DIO mice was recapitulated in cynomolgus monkeys. CONCLUSIONS: Repeated administration of MEDI0382 elicits profound weight loss in DIO mice and non-human primates, produces robust glucose control and reduces hepatic fat content and fasting insulin and glucose levels. The balance of activities at the GLP-1 and glucagon receptors is considered to be optimal for achieving weight and glucose control in overweight or obese Type 2 diabetic patients. PMID- 27377055 TI - Involvement of EGF receptor signaling and NLRP12 inflammasome in fine particulate matter-induced lung inflammation in mice. AB - Epidemiological studies have shown that exposure to ambient fine particulate matter (PM2.5 ) is associated with respiratory diseases. Lung inflammation is a central feature of many pulmonary diseases, which can be induced by PM2.5 exposure. However, the mechanisms underlying PM2.5 -induced lung inflammation remain unclear. To characterize the role of epidermal growth factor receptor (EGFR) and inflammasome in PM2.5 -induced lung inflammation in mice, 30 BALB/c mice were intrabroncheally instilled with saline and PM2.5 suspension (4.0 mg/kg b.w.) for 5 consecutive days, respectively. Bronchoalveolar lavage (BAL) was conducted and BAL fluid (BALF) was collected. The levels of reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), epidermal growth factor (EGF), CXCL1, interleukin (IL)-1beta, and IL-18 in BALF were determined using ELISA. mRNA levels of IL-6, IL-1beta, IL-18, CXCL1, IL-10, NLRP3, Caspase-1, and NLRP12 in lung tissues were determined by RT-PCR. Phospho-EGFR (Tyr1068) and phospho-Akt (Thr308) in lung tissues were examined using immunohistochemical staining and Western blotting, respectively. Protein levels of Caspase-1, NLRP3, NF-kappaB-p52/p100, and NF-kappaB-p65 in bronchial epithelium were examined using immunohistochemical staining. It was shown that PM2.5 exposure induced lung inflammation. Levels of total protein, ROS, iNOS, EGF, and CXCL1 and cell number in the BALF of mice exposed to PM2.5 were markedly elevated relative to the control. mRNA levels of CXCL1, IL-1beta, and IL-18 in lung tissues of PM2.5 exposed mice were increased in comparison with the control. However, level of NLRP12 mRNA in lung tissues of PM2.5 -exposed mice was reduced. Phospho-EGFR (Tyr1068) and phospho-Akt (Thr308) levels in the lungs of PM2.5 -instilled mice were higher than those in the lungs of the control. The protein levels of NF kappaB-p52/p100 and NF-kappaB-p65 in bronchial epithelium of PM2.5 -exposed mice were also increased compared with the control. This study suggests that EGF-EGFR Akt-NF-kappaB signaling and NLRP12 inflammasome may be associated with PM2.5 induced lung inflammation in mice. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1121-1134, 2017. PMID- 27377056 TI - A novel oxime-derived 3d-4f single-molecule magnet exhibiting two single-ion magnetic relaxations. AB - A new oxime-derived {DyNi} cluster with a paramagnetic butterfly-shaped Dy core and peripheral diamagnetic planar-square Ni(II) ions was solvothermally synthesized. The weak ferromagnetically coupled cluster exhibits field-induced single-molecule magnetic behavior with two thermally activated single-ion relaxations. PMID- 27377057 TI - Erratum: Secondary reconstruction of vaginal stenosis using a posterior labial perforator based Falandry flap. AB - [This corrects the article DOI: 10.11604/pamj.2015.21.185.6559.]. PMID- 27377058 TI - Phosphate bioisostere containing amphiphiles: a novel class of squaramide-based lipids. AB - We describe a novel class of amphiphiles with squaramide moiety as a phosphate bioisostere. Most synthesized squaramide-based amphiphiles have the favorable physicochemical properties of lipids, such as: formation of stable liposomes or giant unilamellar vesicles in aqueous solution, high phase-transition temperature, low vesicle leakage and phospholipase resistance properties. PMID- 27377059 TI - Adenocarcinoma risk in patients registered with Polish Barrett's Oesophagus Registry. AB - Barrett's Oesophagus (BO) is a complication of chronic gastro-oesophageal reflux disease (GORD) and is a major risk factor for oesophageal adenocarcinoma. Current guidelines are based on data showing a 0.5% annual malignancy progression rate. The Polish Barrett's Oesophagus Registry (POBOR) was established to characterize Polish patients with BO and estimate the risk of malignant progression. POBOR was established in 1999 after a dedicated training of endoscopists and histopathologists. Physicians registered patients using a dedicated registry form. After excluding patients known to have endoscopic treatment for BO, follow up <1 year and adenocarcinoma found at index endoscopy we have linked patients personal identification numbers (PESEL) with the National Cancer Registry to identify those with a diagnosis of oesophageal or gastric cardia adenocarcinoma. In total, 843 patients were registered [609 men (72.2%), male to female ratio 2.6:1] with median age at diagnosis of 56 years (IQR:47-67). Long segment BE was found at index endoscopy in 294 patients (39.4%) whereas low grade dysplasia in 147 (17.4%). 112 patients (13.3%) fulfilled the exclusion criteria and the remaining 731 were followed for a median of 9.8 years (IQR: 9.3-10.0). After 6779 patient-years, 6 adenocarcinomas were diagnosed yielding an incidence rate of 0.89 per 1000 patients-years (95% confidence interval [CI 0.40-1.97]) which corresponds to annual malignancy progression rate of less than 0.1%. The malignancy rate in patients with low grade dysplasia was 3.70 per 1000 patient years (95% CI 1.39-9.85). In Polish BO patients the risk of malignant progression was lower than previously reported. It was notably higher in patients with low grade dysplasia than in those with no dysplasia at index endoscopy, which may warrant strict surveillance in these patients. PMID- 27377060 TI - Hormone concentrations throughout uncomplicated pregnancies: a longitudinal study. AB - BACKGROUND: Evidence suggests that the hormonal milieu of pregnancy is an important determinant of subsequent cancer and other chronic diseases in both the mother and the offspring. Many of the existing maternity and birth cohorts include specimens drawn only once during pregnancy. How well a single blood specimen collected during a pregnancy characterizes exposure to these hormones throughout gestation, and also in subsequent pregnancies, is not well understood. METHODS: We used serial serum samples from 71 pregnant women (25 primiparous, 25 multiparous, and 21 with two consecutive pregnancies) with natural, complication free pregnancies and a healthy offspring at term who participated in a population based screening trial for congenital infections in Finland between January 1st, 1988 and June 30, 1989 and provided a blood sample in each trimester. RESULTS: Hormone levels were more strongly correlated between consecutive trimesters of a pregnancy than between the 1st and 3rd trimester (e.g., estradiol, rT1 vs. T2 = 0.51 and rT2 vs. T3 = 0.60, p < 0.01; rT1 vs. T3 = 0.32, p < 0.05). Concentrations of sRANKL remained stable throughout gestation, whereas estradiol, estrone, progesterone, testosterone, prolactin, and osteoprotegerin increased throughout pregnancy. First trimester hormone concentrations explained less of the variation in the third trimester on their own than second trimester hormone levels (e.g. estradiol R(2) T1 = 16 % and R(2) T2 = 42 %). Addition of maternal (e.g., smoking) and/or child characteristics (e.g., sex) improved the accuracy of the 3rd trimester estimates for some of the hormones. CONCLUSIONS: One hormone measurement in early pregnancy, in conjunction with maternal and fetal characteristics, permits estimation of 3rd trimester hormone concentrations. Therefore, single hormone measurements available from maternity cohorts are suitable to quantify hormone exposure during pregnancy. To our knowledge, we provide the first data on correlations between hormone concentrations both across trimesters of a single pregnancy, as well as between two subsequent pregnancies. PMID- 27377061 TI - Expansive hematoma in delayed cerebral radiation necrosis in patients treated with T-DM1: a report of two cases. AB - BACKGROUND: Multiple new targeted agents have been developed for patients with human epidermal growth factor receptor type 2 (HER2) - positive breast cancer. Patients with HER2- positive breast cancer will develop brain metastases with greater incidence than patients with non-HER2 cancers, and many of them will undergo stereotactic radiosurgery (SRS) or other CNS radiotherapy. The interaction between radiation effects and new targeted agents is not well understood. We report two cases suggesting a novel adverse effect of T-DM1 (trastuzumab emtansine) on symptomatic enlargement of radiation necrosis (RN) after SRS. CASE PRESENTATION: Two patients with HER2-positive breast cancer had received SRS for single brain metastasis more than 5-years ago. They had been heavily treated for HER2-positive metastatic breast cancer (trastuzumab and pacritaxel, lapatinib and capecitabine). They initiated T-DM1 therapy for progressive systematic disease 5.5 years after stereotactic irradiation, when a small RN was recognized on brain MR images of each patient. The RN lesions increased in size and became symptomatic during 13 or 14 months of T-DM1 treatment. The patients underwent surgical resection of the lesion. Pathological examination revealed necrosis, hematoma, granulation tissue and telangiectasia without neoplastic cells. CONCLUSIONS: A potential enhancement of RN by T-DM1 in the brain may be one of important adverse events associated with the use of T-DM1 for patients after SRS. These cases highlight the need of careful follow-up when combining new systemic targeted therapies and SRS for brain metastases. PMID- 27377062 TI - Association between trial registration and treatment effect estimates: a meta epidemiological study. AB - BACKGROUND: To increase transparency in research, the International Committee of Medical Journal Editors required, in 2005, prospective registration of clinical trials as a condition to publication. However, many trials remain unregistered or retrospectively registered. We aimed to assess the association between trial prospective registration and treatment effect estimates. METHODS: This is a meta epidemiological study based on all Cochrane reviews published between March 2011 and September 2014 with meta-analyses of a binary outcome including three or more randomised controlled trials published after 2006. We extracted trial general characteristics and results from the Cochrane reviews. For each trial, we searched for registration in the report's full text, contacted the corresponding author if not reported and searched ClinicalTrials.gov and the International Clinical Trials Registry Platform in case of no response. We classified each trial as prospectively registered (i.e. registered before the start date); retrospectively registered, distinguishing trials registered before and after the primary completion date; and not registered. Treatment effect estimates of prospectively registered and other trials were compared by the ratio of odds ratio (ROR) (ROR <1 indicates larger effects in trials not prospectively registered). RESULTS: We identified 67 meta-analyses (322 trials). Overall, 225/322 trials (70 %) were registered, 74 (33 %) prospectively and 142 (63 %) retrospectively; 88 were registered before the primary completion date and 54 after. Unregistered or retrospectively registered trials tended to show larger treatment effect estimates than prospectively registered trials (combined ROR = 0.81, 95 % CI 0.65-1.02, based on 32 contributing meta-analyses). Trials unregistered or registered after the primary completion date tended to show larger treatment effect estimates than those registered before this date (combined ROR = 0.84, 95 % CI 0.71-1.01, based on 43 contributing meta-analyses). CONCLUSIONS: Lack of trial prospective registration may be associated with larger treatment effect estimates. PMID- 27377063 TI - Quantification by real-time PCR of Trypanosoma cruzi DNA in samples of Triatoma infestans used in xenodiagnosis of chronic Chagas disease patients. AB - BACKGROUND: Trypanosoma cruzi multiplies and differentiates in the digestive tract of triatomine insects. Xenodiagnosis (XD) is a parasitological tool in which the insect vectors acts as a biological culture medium to amplify and detect T. cruzi infection in mammals. The sensitivity of XD has been overcome by the application of PCR in fecal samples (FS) of XD (PCR-XD). In this study, T. cruzi amplified in Triatoma infestans fed by XD on individuals with chronic Chagas disease (CChD) is quantified by real-time PCR (qPCR-XD). FINDINGS: Under informed consent, 100 individuals were evaluated. In 21 of them XD, PCR-XD and qPCR-XD were positive. For the contrary, 79 were negative XD. In 58 (73.4 %) and 66 cases (83.5 %) of them, PCR-XD (Fisher's exact test P = 0.005) and qPCR-XD (Fisher's exact test: P = 0.037) respectively, were positive. In cases with positive XD, qPCR-XD allowed to establish that in 9/21 cases (42.9 %) the parasite burden fluctuated between 100 and 1,000 par. eq./ml. Otherwise, in 32/79 (40.5 %) cases with negative XD, a parasite burden between 1 and 10 par. eq./ml was determined. All samples showed amplification of exogenous internal control (X12, Ct average: 31.8), so problems in the DNA extraction (excess or loss of genetic material), unspecific amplification and/or inhibition in qPCR-XD reactions were ruled out. Additionally, in all the patients qPCR in blood (qPCR B) was performed. In the cases with positive XD, the concordance between the positivity of qPCR-XD and qPCR-B was 100 %, nevertheless, the parasite burden in blood was lower and different than XD (Chi-square test: chi (2) = 91.82, df = 5, P = 0.0001). In the cases with negative XD the ranges of qPCR-XD and qPCR-B were similar (Chi-square test: chi (2) = 6.71, df = 5, P = 0.1520). CONCLUSIONS: This study allowed the detection and quantification of T. cruzi by qPCR-XD in FS of Tr. infestans fed on patients with CChD. The highest parasite burden was observed in positive XD cases. qPCR-XD could be used in different studies related with the complex T. cruzi-vector-host interactions. PMID- 27377065 TI - Disclosing drug companies payments should be compulsory, say top earners. PMID- 27377064 TI - Retrovirus Integration Database (RID): a public database for retroviral insertion sites into host genomes. AB - The NCI Retrovirus Integration Database is a MySql-based relational database created for storing and retrieving comprehensive information about retroviral integration sites, primarily, but not exclusively, HIV-1. The database is accessible to the public for submission or extraction of data originating from experiments aimed at collecting information related to retroviral integration sites including: the site of integration into the host genome, the virus family and subtype, the origin of the sample, gene exons/introns associated with integration, and proviral orientation. Information about the references from which the data were collected is also stored in the database. Tools are built into the website that can be used to map the integration sites to UCSC genome browser, to plot the integration site patterns on a chromosome, and to display provirus LTRs in their inserted genome sequence. The website is robust, user friendly, and allows users to query the database and analyze the data dynamically. AVAILABILITY: https://rid.ncifcrf.gov ; or http://home.ncifcrf.gov/hivdrp/resources.htm . PMID- 27377066 TI - Cardiovascular risk factors and inflammatory activity among centenarians with and without dementia. AB - A better knowledge of the differences existing between individuals who maintain cognition up to 100 years of age or more and those of the same age who present dementia syndrome may be of help in understanding the dementia of the very elderly people. The aim of this study was to assess cardiovascular risk factors and inflammatory markers among centenarians with and without dementia. A population-based cross-sectional study was conducted on centenarians residing in a middle-size city. Volunteers were evaluated by comprehensive geriatric assessment at home. General laboratory examinations were performed and cardiovascular risk and inflammatory activity markers were determined. Mean subject age was 101 +/- 2 years, and 82 % were women. Assessment of dementia syndrome revealed that 36.4 % of the centenarians had preserved cognition. Centenarians with dementia had lower schooling (p < 0.01), lower body mass index (p = 0.02) and higher homocysteine levels (p < 0.01) and tended to have a lower systolic blood pressure (p = 0.05). Regarding the markers of inflammatory activity, demented subjects had high levels of interleukin-6 (p < 0.01), high sensitivity C-reactive protein (p = 0.02), and erythrocyte sedimentation rate (p = 0.01) and lower albumin levels (p = 0.02) compared to centenarians without dementia. Concluding, centenarians with preserved cognition had better nutritional status, lower homocysteinemia, tendency to higher blood pressure and lower inflammatory activity compared to demented subjects. PMID- 27377067 TI - L-Ascorbic Acid Protected Against Extrinsic and Intrinsic Apoptosis Induced by Cobalt Nanoparticles Through ROS Attenuation. AB - Currently, tissue damage induced by cobalt nanoparticles (CoNPs) and cobalt ions (Co2+) are the most serious syndrome in the patients with metal-on-metal hip prostheses. Therefore, an urgent need exists for the identification of the mechanisms and the development of therapeutic strategies to limit it. The purpose of this study was to explore the mechanism of this damage and to demonstrate if L ascorbic acid (L-AA) could protect against the cell toxicities induced by CoNPs and Co2+ in vitro. With CoNPs and Co2+ treatment, cell viability was significantly decreased; the ROS (reactive oxygen species) level in mitochondria was dramatically increased in CoNPs treated cells, but cobalt ions could barely induce the ROS. Consistently, the level of cell apoptosis was increased with the upregulation of pro-apoptotic factors (caspases 8, 9, and 3, and Bax) and the downregulation of anti-apoptotic factor Bcl-2. Besides that, the levels of cytochrome c and AIF were increased and released from mitochondria into the cytoplasm. After the cells were pretreated with L-AA, the cell viability decreased by CoNPs was reversed and the ROS induced by CoNPs was suppressed. The level of cell apoptosis induced by CoNPs was decreased as well. But it could not reverse the effects induced by Co2+. These studies demonstrated that CoNPs induce extrinsic and intrinsic apoptotic pathways via generation of ROS, and L-AA could prevent the cytotoxicity by reducing the level of ROS. While Co2+ may induce cytotoxicity through other signals, it could not be protected by L-AA treatment. PMID- 27377068 TI - All laser cataract surgery compared to femtosecond laser phacoemulsification surgery: corneal trauma. AB - The aim of this study was to evaluate corneal tissue trauma after femtosecond laser-assisted cataract surgery (FLACS) and phacoemulsification (femtophaco surgery) compared to FLACS and nanolaser emulsification (all laser surgery). This is a prospective nonrandomized clinical study conducted at the Ophthalmology Clinic, University "G. d'Annunzio" of Chieti-Pescara, Italy, involving forty-two eyes of 42 patients candidates to cataract surgery. Patients were enrolled in two groups: femtophaco surgery (group 1 with 21 eyes) and all laser surgery (group 2 with 21 eyes). Main outcome measures included uncorrected visual acuity and distance corrected visual acuity, corneal endothelial cell count, and corneal thickness at the tunnel site and at the center of the cornea. Best correct visual acuity was not significantly different between the two groups. Postoperatively, a significant decrement of endothelial cell count at the center of the cornea was observed in group 1 compared with preoperative values at 90 days (p < 0.001) while t remained stable in group 2. The central corneal thickness showed a statistically significant increase for both groups that reached a maximum thickness at 7 days and then returned to presurgery levels after 90 days for group 1 and after 60 days for group 2. The tunnel corneal thickness showed a statistically significant increase for both groups that reached a maximum thickness at 7 days, which did not return to presurgery level for group 1 but did return to presurgery levels after 60 days for group 2. All laser surgery induced lower central endothelial cell loss and lower increase of corneal thickness compared to femtophaco surgery. PMID- 27377069 TI - Revisiting the global effect and inhibition of return. AB - Saccades toward previously cued locations have longer latencies than saccades toward other locations, a phenomenon known as inhibition of return (IOR). Watanabe (Exp Brain Res 138:330-342. doi: 10.1007/s002210100709 , 2001) combined IOR with the global effect (where saccade landing points fall in between neighboring objects) to investigate whether IOR can also have a spatial component. When one of two neighboring targets was cued, there was a clear bias away from the cued location. In a condition where both targets were cued, it appeared that the global effect magnitude was similar to the condition without any cues. However, as the latencies in the double cue condition were shorter compared to the no cue condition, it is still an open question whether these results are representative for IOR. Considering the double cue condition can provide valuable insight into the interaction of the mechanisms underlying the two phenomena, here, we revisit this condition in an adapted paradigm. Our paradigm does result in longer latencies for the cued locations, and we find that the magnitude of the global effect is reduced significantly. Unexpectedly, this holds even when only including saccades with the same latencies for both conditions. Thus, the increased latencies associated with IOR cannot directly explain the reduction in global effect. The global effect reduction can likely best be seen as either a result of short-term depression of exogenous visual signals or a result of IOR established at the center of gravity of cues. PMID- 27377070 TI - Near-infrared light treatment reduces astrogliosis in MPTP-treated monkeys. AB - We have reported previously that intracranial application of near-infrared light (NIr) reduces clinical signs and offers neuroprotection in a subacute MPTP (1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson's disease. In this study, we explored whether NIr reduces the gliosis in this animal model. Sections of midbrain (containing the substantia nigra pars compacta; SNc) and striatum were processed for glial fibrillary acidic protein (to label astrocytes; GFAP) and ionised calcium-binding adaptor molecule 1 (to label microglia; IBA1) immunohistochemistry. Cell counts were undertaken using stereology, and cell body sizes were measured using ImageJ. Our results showed that NIr treatment reduced dramatically (~75 %) MPTP-induced astrogliosis in both the SNc and striatum. Among microglia, however, NIr had a more limited impact in both nuclei; although there was a reduction in overall cell size, there were no changes in the number of microglia in the MPTP-treated monkeys after NIr treatment. In summary, we showed that NIr treatment influenced the glial response, particularly that of the astrocytes, in our monkey MPTP model of Parkinson's disease. Our findings raise the possibility of glial cells as a future therapeutic target using NIr. PMID- 27377072 TI - The value of sound waves and pleural manometry in diagnosing a pleural effusion with the dual diagnosis. PMID- 27377071 TI - Retention during capsule endoscopy: Is it a real problem in routine practice? AB - OBJECTIVE: This study evaluated the risks and outcomes of capsule retention during capsule endoscopy (CE) for investigating small bowel disease. Capsule retention is the most serious complication of CE. METHODS: Before CE, the gastrointestinal tract was evaluated for blockages with computerized tomography. Analysis of CE was made retrospectively. RESULTS: Capsule endoscopy was used to investigate obscure bleeding (90.2%; n = 324) or other symptoms (9.8%; n = 35). The capsule retention rate was 11/359 (3.1%); it was retained in a malignant lesion area (adenocarcinoma or melanoma) in two patients (18.2%), in the small bowel in an ulcerated area in five patients (45.5%), and in the oesophagus/stomach in four patients (36.4%) due to dysmotility. None of the patients had symptoms of obstruction. CONCLUSIONS: Scanning patients before CE did not predict capsule retention. Retention is a complication of CE, but occurs as a result of the underlying disease. The risk of retention is increased in patients with motility disorders, suspected small bowel ulcers or malignancies. PMID- 27377073 TI - BREATHER (PENTA 16) short-cycle therapy (SCT) (5 days on/2 days off) in young people with chronic human immunodeficiency virus infection: an open, randomised, parallel-group Phase II/III trial. AB - BACKGROUND: For human immunodeficiency virus (HIV)-infected adolescents facing lifelong antiretroviral therapy (ART), short-cycle therapy (SCT) with long-acting agents offers the potential for drug-free weekends, less toxicity, better adherence and cost savings. OBJECTIVES: To determine whether or not efavirenz (EFV)-based ART in short cycles of 5 days on and 2 days off is as efficacious (in maintaining virological suppression) as continuous EFV-based ART (continuous therapy; CT). Secondary objectives included the occurrence of new clinical HIV events or death, changes in immunological status, emergence of HIV drug resistance, drug toxicity and changes in therapy. DESIGN: Open, randomised, non inferiority trial. SETTING: Europe, Thailand, Uganda, Argentina and the USA. PARTICIPANTS: Young people (aged 8-24 years) on EFV plus two nucleoside reverse transcriptase inhibitors and with a HIV-1 ribonucleic acid level [viral load (VL)] of < 50 copies/ml for > 12 months. INTERVENTIONS: Young people were randomised to continue daily ART (CT) or change to SCT (5 days on, 2 days off ART). MAIN OUTCOME MEASURES: Follow-up was for a minimum of 48 weeks (0, 4 and 12 weeks and then 12-weekly visits). The primary outcome was the difference between arms in the proportion with VL > 50 copies/ml (confirmed) by 48 weeks, estimated using the Kaplan-Meier method (12% non-inferiority margin) adjusted for region and age. RESULTS: In total, 199 young people (11 countries) were randomised (n = 99 SCT group, n = 100 CT group) and followed for a median of 86 weeks. Overall, 53% were male; the median age was 14 years (21% >= 18 years); 13% were from the UK, 56% were black, 19% were Asian and 21% were Caucasian; and the median CD4% and CD4 count were 34% and 735 cells/mm(3), respectively. By week 48, only one participant (CT) was lost to follow-up. The SCT arm had a 27% decreased drug exposure as measured by the adherence questionnaire and a MEMSCap(TM) Medication Event Monitoring System (MEMSCap Inc., Durham, NC, USA) substudy (median cap openings per week: SCT group, n = 5; CT group, n = 7). By 48 weeks, six participants in the SCT group and seven in the CT group had a confirmed VL > 50 copies/ml [difference -1.2%, 90% confidence interval (CI) -7.3% to 4.9%] and two in the SCT group and four in the CT group had a confirmed VL > 400 copies/ml (difference -2.1%, 90% CI -6.2% to 1.9%). All six participants in the SCT group with a VL > 50 copies/ml resumed daily ART, of whom five were resuppressed, three were on the same regimen and two with a switch; two others on SCT resumed daily ART for other reasons. Overall, three participants in the SCT group and nine in the CT group (p = 0.1) changed ART regimen, five because of toxicity, four for simplification reasons, two because of compliance issues and one because of VL failure. Seven young people (SCT group, n = 2; CT group, n = 5) had major non nucleoside reverse transcriptase inhibitor mutations at VL failure, of whom two (n = 1 SCT group, n = 1 CT group) had the M184V mutation. Two young people had new Centers for Disease Control B events (SCT group, n = 1; CT group, n = 1). There were no significant differences between SCT and CT in grade 3/4 adverse events (13 vs. 14) or in serious adverse events (7 vs. 6); there were fewer ART related adverse events in the SCT arm (2 vs. 14; p = 0.02). At week 48 there was no evidence that SCT led to increased inflammation using an extensive panel of markers. Young people expressed a strong preference for SCT in a qualitative substudy and in pre- and post-trial questionnaires. In total, 98% of the young people are taking part in a 2-year follow-up extension of the trial. CONCLUSIONS: Non-inferiority of VL suppression in young people on EFV-based first-line ART with a VL of < 50 copies/ml was demonstrated for SCT compared with CT, with similar resistance, safety and inflammatory marker profiles. The SCT group had fewer ART-related adverse events. Further evaluation of the immunological and virological impact of SCT is ongoing. A limitation of the trial is that the results cannot be generalised to settings where VL monitoring is either not available or infrequent, nor to use of low-dose EFV. Two-year extended follow-up of the trial is ongoing to confirm the durability of the SCT strategy. Further trials of SCT in settings with infrequent VL monitoring and with other antiretroviral drugs such as tenofovir alafenamide, which has a long intracellular half-life, and/or dolutegravir, which has a higher barrier to resistance, are planned. TRIAL REGISTRATION: Current Controlled Trials ISRCTN97755073; EUDRACT 2009-012947-40; and CTA 27505/0005/001-0001. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (projects 08/53/25 and 11/136/108), the European Commission through EuroCoord (FP7/2007/2015), the Economic and Social Research Council, the PENTA Foundation, the Medical Research Council and INSERM SC10-US19, France, and will be published in full in Health Technology Assessment; Vol. 20, No. 49. See the NIHR Journals Library website for further project information. PMID- 27377074 TI - Predictors of sinus rhythm after electrical cardioversion of atrial fibrillation: results from a data mining project on the Flec-SL trial data set. AB - Aims: Data mining is the computational process to obtain information from a data set and transform it for further use. Herein, through data mining with supportive statistical analyses, we identified and consolidated variables of the Flecainide Short-Long (Flec-SL-AFNET 3) trial dataset that are associated with the primary outcome of the trial, recurrence of persistent atrial fibrillation (AF) or death. Methods and results: The 'Ranking Instances by Maximizing the Area under the ROC Curve' (RIMARC) algorithm was applied to build a classifier that can predict the primary outcome by using variables in the Flec-SL dataset. The primary outcome was time to persistent AF or death. The RIMARC algorithm calculated the predictive weights of each variable in the Flec-SL dataset for the primary outcome. Among the initial 21 parameters, 6 variables were identified by the RIMARC algorithm. In univariate Cox regression analysis of these variables, increased heart rate during AF and successful pharmacological conversion (PC) to sinus rhythm (SR) were found to be significant predictors. Multivariate Cox regression analysis revealed successful PC as the single relevant predictor of SR maintenance. The primary outcome risk was 3.14 times (95% CI:1.7-5.81) lower in those who had successful PC to SR than those who needed electrical cardioversion. Conclusions: Pharmacological conversion of persistent AF with flecainide without the need for electrical cardioversion is a powerful and independent predictor of maintenance of SR. A strategy of flecainide pretreatment for 48 h prior to planned electrical cardioversion may be a useful planning of a strategy of long term rhythm control. PMID- 27377075 TI - Contact-force-guided vs. contact-force-blinded catheter ablation of typical atrial flutter: a prospective study. AB - Aims: It remains unknown whether contact force (CF) sensing technology is of value for cavotricuspid isthmus (CTI) ablation. We prospectively evaluated procedural parameters and outcomes of CF-guided vs. CF-blinded CTI ablation for typical atrial flutter (AFL). Methods and results: A total of 70 consecutive patients (62.5 +/- 10.9 years) undergoing CTI ablation for AFL were prospectively enrolled, 35 in CF-blinded and 35 in CF-guided groups. A CF-sensing catheter (power 25-35 W) was used in all. In the CF-guided group, CF target range was 10 25 g, whereas in the CF-blinded group, the operator was blinded to CF. The isthmus was divided into anterior, middle, and posterior segments for region specific CF analysis. The procedural endpoint of bidirectional isthmus block following a 20-min observation period was achieved in all. A trend towards lower fluoroscopy and procedure duration was observed when the CF-guided group was compared with the CF-blinded group. The total radiofrequency (RF) energy delivery time required to achieve bidirectional block was significantly lower in the CF guided vs. CF-blinded group [10.0 min (IQR 8.3;15.1) vs. 15.9 min (IQR 9.6;24.7), P= 0.0020], with a significant inverse correlation between CF and total RF delivery time (r = -0.36; P= 0.0027). Mean CF measurements significantly increased from anterior to posterior anatomical zones of CTI in the CF-blinded group (ANOVA P= 0.0466). Conclusions: Catheter ablation of AFL guided by real time CF assessment results in a significant reduction in total RF delivery time. Real-time CF measurements facilitate the maintenance of homogenous efficient contact all along the CTI, particularly in the anterior segment where CF is generally lower. PMID- 27377076 TI - All that wheezes is not asthma: adult tracheomalacia resulting from innominate artery compression. PMID- 27377077 TI - A snapshot survey of perceptions of healthcare professionals on ageing surgeons. AB - OBJECTIVE: The aim of this research was to understand healthcare professionals' perception of the continued practice of ageing surgeons in Singapore. METHODOLOGY: A quantitative method was chosen for this research to determine healthcare professionals' perception of the practice of ageing surgeons. Ethical approval was obtained from the local ethical review board. A cross-sectional method using a population survey was performed among healthcare professionals in two tertiary institutions and the study was confined to stakeholders in practices of ageing surgeons. The population sampled was limited to nurses in the theatre, anaesthetists, surgeons and geriatricians (physicians). An online questionnaire was designed for the survey that took into consideration the various conceptual frameworks of ageing surgeons' practice that was obtained from a literature review. RESULTS: There were 104 respondents of a population of 350 sampled (theatre nurses, anaesthetists, physicians and surgeons) giving a respondent rate of 30%. The mean age of the participants was 39.7; 72% were doctors (surgeons 34%, physicians 20% and anaesthetists 18%) and 28% nurses. Only 35% agreed with the statement that older surgeons face deterioration in cognitive faculties and 29% remained neutral. A similar trend was seen with the perception that older surgeons face a decline in memory. However, 44% agreed with the statement that older surgeons face a decline in visuospatial ability and another 40% agreed that they had a decline in psychomotor skills and reaction time. Fifty per cent agreed with the statement that they face deterioration in physical abilities. Sixty three per cent did not think that older surgeons face a decline in reasoning and judgement. Forty-eight per cent believed that older surgeons' vast fund of knowledge and experience could compensate for physical and cognitive changes. Only 13% agreed with the statement that older surgeons have higher surgical mortality. Forty-five per cent agreed that the retirement age should be 65 while 22% believed it should be over 65. Forty-four per cent agreed that a regular multidisciplinary, objective and comprehensive evaluation of an older surgeon's physical and cognitive function would help to identify and treat reversible problems which when corrected would aid in restoring the surgeon's function. Seventy-four per cent felt that it was the responsibility of all stakeholders to decide or report on when an ageing surgeon is unsafe to continue practicing. Fifty-five per cent disagreed with a mandatory retirement age for surgeons. CONCLUSIONS: This study showed that, in Singapore, stakeholders agreed there are changes in physical and cognitive abilities of ageing surgeons but they thought that these can be overcome with selective strategies to optimise their role in the workforce. They also disagreed on a mandatory retirement age. PMID- 27377079 TI - Prognostic impact of ReTURB in high grade T1 primary bladder cancer. AB - PURPOSE: To evaluate whether pathological outcomes of ReTURB have a prognostic impact on recurrence and progression of primitive T1HG bladder cancer. MATERIAL AND METHODS: Patients affected by primitive T1HG TCC of bladder underwent restaging TURB (ReTURB). Patients with muscle invasive disease at ReTURB underwent radical cystectomy; those with non-muscle invasive residual (NMI-RT) and those with no residual tumour (NRT) received an intravesical BCG therapy. We compared recurrence and progression in NMIRT patients and NRT patients at restaging TURB. Patients were followed every 3-6 months with cystoscopy and urine cytology. RESULTS: 212 patients were enrolled in the study. At ReTURB, residual cancer was detected in 92 of 196 (46.9%) valuable patients: 14.3% of these were upstaged to T2. At follow up of 26.3 +/- 22.8 months, there were differences in recurrence and progression rates between NRT and NMIRT patients: 26.9% and 45.3% (p < 0.001), 10.6% and 23.4% (p 0.03), respectively. Recurrence-free and progression-free survivals were significantly higher in NRT compared to NMIRT patients: 73.1% and 54.7% (p < 0.001), 89.4% and 76.6 (p 0.03), respectively. CONCLUSIONS: ReTURB allows to identify a considerable number of residual and understaged cancer. Patients with NMIRT on ReTURB have worse prognosis than those with NRT in terms of recurrence and progression free survival. These outcomes seem to suggest a prognostic impact of findings on ReTURB that could be a valid tool in management of high grade T1 TCC. PMID- 27377078 TI - The Related Risk Factors Analysis of Snake-Bite Induced Acute Kidney Injury. AB - BACKGROUND The pathogenic mechanism of snake-bite induced acute kidney injury (AKI) remains unclear. Analyzing the risk factors for snake-bite induced AKI may provide the guidance needed for AKI prevention and early treatment. MATERIAL AND METHODS This retrospective study included 119 snake-bite patients who were hospitalized at the emergency department of Sichuan Provincial People's Hospital from January 2011 to September 2013. The patients were divided into AKI and non AKI groups according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guideline. Gender, age, and clinical examination data of the patients were recorded. The Mann-Whitney U test and Fisher exact test were performed to analyze the collected data; preliminary analysis of independent risk factors was performed with multivariate logistic regression. RESULTS Among the snake-bite patients, 98.3% were farmers. The mean age of patients was 46+/-12 years. Of the 119 patients (13.4%), 16 suffered from AKI. There were statistically significant differences between the AKI and non-AKI groups with respect to age, time interval from snake bite to antivenin therapy, creatine kinase, blood myoglobin, advanced age, regional lymphadenopathy, incision drainage, and hemoglobin. Preliminary analysis with multivariate logistic regression showed that advanced age and increased time interval from snake bite to antivenin therapy might be independent risk factors for snake-bite induced AKI. CONCLUSIONS Age, time interval from snake bite to antivenin therapy, creatine kinase, blood myoglobin, advanced age, regional lymphadenopathy, incision drainage, and hemoglobin were risk factors for snake-bite induced AKI. Advanced age and delayed antivenin therapy might be independent risk factors for snake-bite induced AKI. PMID- 27377080 TI - Is a second look necessary in multiple and/or large Ta tumors? AB - INTRODUCTION: Most of the bladder cancers are tumors without muscle invasion at the time of diagnosis. Transurethral resection is the standard treatment in bladder tumors without muscle invasion. Proper review of transurethral resection is important for correct risk classification. In this study, our main objective was to show that a "second look" in patients with multiple and/or > 3 cm tumors regardless of T stage during the early term can be helpful in detection of possible residues and determining risk classification. MATERIALS AND METHODS: 156 patients with primary, multiple and/or > 3 cm tumors were included in the study. Patients were divided into 3 groups as Group 1 (Ta), Group 2 (T1 without second TUR) and Group 3 (T1 with second TUR). Macroscopic tumor occurrence rates were compared in their 3rd month control cystoscopy. RESULTS: Macroscopic tumor detection rates in patients' 3rd month control cystoscopy were 21 (46.7%) in Group 1, 18 (30%) in Group 2 and 4 (7.8%) in Group 3. When compared with Group 3 patients, Group 1 and Group 2 had higher statistically significant macroscopic tumor detection rates (p = 0.001) CONCLUSION: A second look in patients with multiple and/or > 3 cm tumors during early term will enable the surgeons to detect possible tumors and do a better job in risk classification. PMID- 27377081 TI - Can perineural invasion detected in prostate needle biopsy specimens predict surgical margin positivity in D'Amico low risk patients? AB - OBJECTIVES: In this study, our aim was to estimate the value of perineural invasion (PNI) in prostate needle biopsy (PNB) specimens in the prediction of surgical margin positivity (SMP) and its prognostic significance (upgrade Gleason Score) in patients who had undergone radical retropubic prostatectomy (RRP) with low risk prostate cancer according to D'Amico risk assessment. MATERIALS AND METHODS: We retrospectively analyzed the data of 65 patients who were diagnosed as clinical stage T1c prostate cancer (PC) and underwent RRP between January 2010 and June 2013. Pathological specimens of PNB and RRP were separately examined for the parameters of PNI, vascular invasion (VI), Gleason Score (GS) and SMP. RESULTS: The patients' mean age was 63.65 +/- 4.93 (range 47- 75) years. PNI in PNB specimens were identified in 12 of 65 patients and 11 of 12 patients showed SMP on RRP specimens. While 53 of 65 patients had not PNI on PNB, only 11 of them demonstrated SMP on RRP specimens. SMP was 30.64-fold more frequently encountered in PNB specimens obtained from PNI-positive patients relative to PNI-negative patients. In our study, PNI detected in PNB specimens was statistically significantly associated with SMP on RRP specimens (P = 0.0001). CONCLUSION: It is well known that higher PSA values and GS were independent predictors of SMP in clinically localized prostate cancer (CLPC). We think that PNI in PNB specimens may be a useful prognostic factor for predicting SMP in cases with CLPC. PMID- 27377082 TI - Safety and efficacy of percutaneous nephrolithotomy in the Galdakao - Modified Supine Valdivia position: A prospective analysis. AB - OBJECTIVE: Aim of the present study was to evaluate the safety and efficacy of Percutaneous Nephrolithotomy (PCNL) in the Galdakao- Modified Supine Valdivia (GMSV) position in order to predict operative time, stone-free rate and onset of complications taking into account comorbidity, stone-related parameters and anatomic upper urinary tract abnormalities. MATERIAL AND METHODS: A prospective evaluation of patients who underwent to PCNL in GMSV position for renal stones > 2 cm, from January 2009 to February 2015 was performed. According to the technique, upper urinary tract abnormalities, stone chemical and morphological characteristics, and patients' history were matched with operative outcome, in terms of stone-free, intervention time and incidence of perioperative complications. RESULTS: Seventy-two cases were collected; mean operative time was 105 minutes (DS 41): staghorn stones and the presence of comorbidity resulted statistically significant variables. The complication-rate resulted in line with data showed in literature: hyperpyrexia and hemorrhage were the more frequently complications found. The overall stone-free was reached in 48 patients (67%), and it was influenced by patients' anatomic abnormalities. CONCLUSIONS: In the treatment of renal stones, PCNL may be a safe and effective choice; nevertheless, patients' anatomic abnormalities or staghorn-stones may influence the outcomes. Thus, a prospective study with a larger population is needed to verify our outcomes. PMID- 27377083 TI - The management of total avulsion of the ureter from both ends: Our experience and literature review. AB - OBJECTIVE: To evaluate the treatment modalities of total ureteral avulsion and to clarify the risk factors of this serious complication. METHODS: This study retrospectively analyzed the data of 3 patients with complete ureteral avulsion during ureteroscopy. Of the three patients, two had distal ureteral complete avulsion, and one total ureteral avulsion on both ends. Ureteroneocystostomy (UNC) was immediately performed after distal ureteral avulsion cases. Ileal ureter substition was performed on the same session after the total ureteral avulsion in both ends. Two of the patients were under chronic use of corticosteroid treatment due to diagnosis of idiopathic trombocytopenic purpura and myastenia gravis and all patients had unsuccesful shockwave litotripsy (SWL) treatment history with at least 1 month period before surgery. RESULTS: The patient who had ileal ureter substitution was followed at 3-month intervals by ultrasonography and renal function tests and she was uneventful after a 2 year follow-up period. The patients treated with UNC were followed up at 3 month interval by ultrasonography and renal function tests. They had normal renal function 1 year after the operation CONCLUSION: Complete ureteral avulsion is a rare but severe complication. Treatment modality can vary and ileal ureter can be applied succesfully in the total ureter avulsion in both ends when bladder capacity is not enough for a Boari flap. Failed SWL and/or corticosteroid treatment history of patients seems to increase the risk of the ureteral avulsion. PMID- 27377084 TI - Metabolic assessment of recurrent and first renal calcium oxalate stone formers. AB - OBJECTIVES: This study aimed to demonstrate the dominant role of metabolic disorders in the formation of calcium oxalate stones in patients with recurrent urolithiasis, as well as in patients experiencing their first episode of urolithiasis. PATIENTS AND METHODS: The records of the patients who attended our kidney stone outpatient clinics between 2008 and 2012 were reviewed, and the data of 318 calcium oxalate stone patients who had undergone a metabolic assessment were retrospectively analysed. The patients were divided in two groups. The first group included the patients who presented with their first episode of urolithiasis (Group 1, n = 170), and the second group included patients with recurrent urolithiasis (Group 2, n = 148); intergroup comparisons of metabolic disorders were performed. RESULTS: A significant difference was found between the two groups in mean urine calcium levels (Group 1, 0.25; Group 2, 0.31; p = 0.001); the mean serum calcium level was found to be significantly higher although at less extent in Group 2 (Group 1, 9.4; Group 2, 9.6); p = 0.04). Significant differences were also found in mean urine citrate (Group 1, 481.9; Group 2, 397.2, p < 0.0001) and oxalate levels (Group 1, 22.1; Group 2, 28.5; p < 0.0001) . CONCLUSIONS: This study revealed a metabolic tendency to hypercalciuria in calcium oxalate stone patients, predominantly in those with recurrent calcium oxalate urolithiasis. Urinary oxalate excretion was found to be higher in recurrent urolithiasis in comparison to the first episode of calcium oxalate urolithiasis and urinary citrate excretion lower in recurrent urolithiasis. PMID- 27377085 TI - The effects of stress incontinence surgery on sexual function and life quality of women. AB - OBJECTIVE: To evaluate Transobturator tape (TOT) and Burch colposuspension procedure's effects on sexual functions and life quality. MATERIALS AND METHODS: A total of 81 patients who underwent TOT (n = 49) or Burch (n = 32) with stress incontinence were included in this prospective study. Preoperatively and at postoperative 6 month follow up pad and stress tests, physical examinations, Female Sexual Function Index (FSFI), International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF), Urinary Distress Inventory (UDI-6), Incontinence Impact Questionnaire (IIQ-7) questionnaires were performed. Patient Global Impression of Improvement (PGI-I) questionnare was added postoperatively. RESULTS: According to stress test, success rate was found to be 69% and 45%, in the TOT and Burch groups respectively. Pad test decreased in both groups (p < 0.05). PGI-I scores was higher in the TOT group when compared to Burch group (p = 0.031). ICIQ-SF scores were improved in both TOT (p < 0.0001) and Burch groups (p < 0.012). IUDI-6 and IIQ-7 scores improved only in TOT group. Total FSFI scores did not change in both groups but only in TOT group sexual desire improved. Total FSFI scores did not change in patients that were successful and unsuccessful according to the stress test in both TOT and Burch groups (p < 0.05). CONCLUSIONS: TOT and Burch procedures have no effect on the sexual functions. However TOT improved life quality of patients. PMID- 27377086 TI - The relationship of enuresis nocturna and adenoid hypertrophy. AB - OBJECTIVES: This study was organized to assess the relationship of enuresis nocturna (EN) and upper airway obstruction (UAO) in children. MATERIAL AND METHODS: This study was multi-centrically and prospectively designed including 79 children who presented to a urology clinic with symptoms of EN between January 2013 and February 2014. Sixty-four age-matched children with no history of urological complaints were randomly recruited from children admitted to a pediatric clinic as a control group. All children and parents were asked to fill out a dysfunctional elimination syndrome (DES) questionnaire and children were examined by an ear, nose and throat (ENT) specialist to evaluate the UAO. Descriptive statistics, chisquare and Mann-Whitney-U tests were used to compare variables. RESULTS: The mean ages of the 79 children (48 male, 31 female) in the study group and the 64 children (41 male, 23 female) in the control group were 10.14+/-3.38 and 9.17+/- 2.85, respectively. Family history of the study showed that 19% of the children's mothers, 10% of the children's fathers and 37% of the children's siblings had experienced EN. There was a significant difference between the study and the control groups in terms of urge to urinate, bladder emptying, bowel symptoms and psychological stress. There was also a significant difference between rates of tonsillar hypertrophy and nasopharynx obstruction in the EN group (p = 0.009). CONCLUSION: In this study we found that half of the children with EN had tonsillar hypertrophy, which was significantly higher than in the control group. Further studies are needed to clarify the exact relationship between UAO and EN. PMID- 27377087 TI - Buccal mucosa is a promising graft in Peyronie's disease surgery. Our experience and a brief literature review on autologous grafting materials. AB - AIM: Peyronie's Disease (PD) is an under reported acquired benign condition that, at the moment, is not curable with medical therapy. Surgery represent the gold standard of treatment. Surgical approaches are several and they consist in "plication techniques" or plaque incision/excision with grafting of resulting albuginea defect. Among grafting procedures, albuginea defect substitution with autologous materials demonstrated over the years not inferior results respect to heterologous grafts. Buccal mucosa graft (BMG) is not usually emphasized in many review articles and clinical series are yet limited. METHODS: We present our experience with seventeen plaque incision procedures and BMG in surgical correction of complex penile curvatures due to PD performed in a period of 30 months. Our analyses was focused on buccal mucosa graft characteristics as major determinant of the surgical success. We also conducted a brief literature review on autologous grafting materials used in reconstructive penile surgery for PD. RESULTS: Our cosmetics and functional results consists in a 100% of functional penile straightening with no relapses and 5,8% of de novo erectile dysfunction. Mean age was 56.4 years, mean follow-up of 22.5 (6-36) months. No complications graft related were observed. Operative time was 115.3 minutes in mean. Over 94% of patients referred they were "really much better" and "much better" satisfied based on PGI-I questionnaire administrated at the last follow- up visit. CONCLUSION: BMG is revealing as an optimal choice for reconstructive surgery in PD. Anatomical characteristics consisting in the great elasticity, the quick integration time and the easy harvesting technique lead to high cosmetics and functional success rate, without omitting economical and invasiveness aspects. PMID- 27377088 TI - INSIST-ED: Italian Society of Andrology registry on penile prosthesis surgery. First data analysis. AB - OBJECTIVES: The Italian Society of Andrology, i.e. "Societa Italiana di Andrologia" (S.I.A.), launched on December 2014 a prospective, multicenter, monitored and internal review board approved Registry for penile implants, the "INSIST-ED" (Italian Nationwide Systematic Inventarisation of Surgical Treatment for ED) Registry. Purpose of this first report is to present a baseline data analysis of the characteristics of penile implant surgery in Italy. MATERIAL AND METHODS: The INSIST-ED Registry is open to all surgeons implanting penile prostheses (all brands, all models) in Italy, providing anonymous patient, device, surgical procedure, outcome, follow-up data, for both first and revision surgeries. A Registry project Board overviews all the steps of the project, and a Registry Monitor interacts with the Registry implanting surgeons. RESULTS: As by April 8, 2016, 31 implanting surgeons actively joined the Registry, entering 367 surgical procedures in its database, that comprise: 310 first implants, 43 prosthesis substitutions, 14 device explants without substitution. Implanted devices account for: 288 three-component devices (81,3%), 20 two-component devices (5,4%), 45 non-hydraulic devices (12,3%). Leading primary ED etiologies in first implant surgeries resulted: former radical pelvic surgery in 111 cases (35,8%), Peyronie's disease in 66 cases (21,3%), diabetes in 39 cases (12,6%). Two intraoperative complications have been recorded. Main reasons for 57 revision surgeries were: device failure (52,6%), erosion (19,3%), infection (12,3%), patient dissatisfaction (10,5%). Surgical settings for patients undergoing a first penile implant were: public hospitals in 251 cases (81%), private environments in 59 cases (19%). CONCLUSIONS: The INSIST-ED Registry represents the first European experience of penile prosthesis Registry. This baseline data analysis shows that: three-pieces inflatable prosthesis is the most implanted device, leading etiology of erectile dysfunction (ED) in patient receiving a prosthesis is former radical pelvic surgery, primary reason for revision surgery is device failure, primary settings for first penile implant surgery are public hospitals. Evaluation of penile implant impact on recipients quality of life is presently ongoing. PMID- 27377089 TI - A survey on the experience of 136 Italian urologists in the treatment of erectile dysfunction with PDE5 inhibitors and recommendations for the use of Avanafil in the clinical practice. AB - INTRODUCTION: PDE5 inhibitors are the firstline treatment for erectile dysfunction. Although all these drugs share the same mechanism of action, each agent could have different characteristics in terms of selectivity, pharmacokinetics and tolerability profile. MATERIALS AND METHODS: This manuscript illustrates a project, undertaken by the Italian Society of Urology in order to obtain a "snapshot" of the experience of Italian urologists with the use of PDE5 inhibitors in the clinical practice. This project included a survey, targeting a sample of 136 Italian urologists experienced in the treatment of ED, and the organization of a conference of experts who, based on the findings of the survey, the scientific literature and the clinical experience, would define some recommendations for the use of PDE5 inhibitors in clinical practice with a particular focus on Avanafil, the most recent drug in this class. RESULTS: The following recommendations on the use of Avanafil were issued: 1) In patients who are candidates for the use of Avanafil, it is advisable to use the 200-mg dose from the first administration; 2) When used at the highest dose (200 mg), Avanafil shows a favourable tolerability profile with an efficacy similar to that of other agents; 3) The patient should be instructed to take Avanafil on an empty stomach, i.e., 30-45 minutes before or 2 hours after a meal; 4) The efficacy window of Avanafil is between 30 minutes and 6 hours after dosing, which qualifies this molecule as a new drug with an intermediate duration of action; 5) Avanafil at a dose of 50-100 mg/day may be a therapeutic option in chronic rehabilitation. CONCLUSIONS: Among PDE5 inhibitors, Avanafil is a new agent with an intermediate duration of action, characterized by high efficacy and good tolerability even at the highest dose (200 mg). PMID- 27377090 TI - The role of Cajal cells in chronic prostatitis. AB - Types of prostatitis can be defined as groups of syndromes in adult men associated with infectious and noninfectious causes characterized frequently by lower abdominal and perineal signs and diverse clinical symptoms and complications. Etiopathogenesis of chronic prostatitis is not well defined. Moreover, its treatment outcomes are not satisfactory. Presence of c-kit positive interstitial cells in human prostate is already known. It has been demonstrated that these cells can be pacemaker cells which trigger spontaneous slow-wave electrical activity in the prostate and can be responsible for the transport of glandular secretion from acinar cells into major and minor prostatic ducts and finally into urethra. In the light of all these data, when presence of a possible inflammatory pathology is thought to involve prostate that secretes and has a reservoir which drains its secretion (for prostate, prostatic urethra), two points are worth mentioning. Impairment of secretion mechanism and collection of secretion within the organ with reflux of the microbial material from its reservoir back into prostate gland. Both of these potential conditions can be explained by ductal neuromuscular mechanism, which induces secretion. We think that in this neuromuscular mechanism interstitial Cajal cells have an important role in chronic prostatitis. Our hypothesis is that curability of prostatitis is correlated with the number of Cajal cells not subjected to apoptosis. PMID- 27377091 TI - The role of Cucurbita pepo in the management of patients affected by lower urinary tract symptoms due to benign prostatic hyperplasia: A narrative review. AB - OBJECTIVE: Phytotherapeutic compounds are largely used in the treatment of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH) due to low side-effect profiles and costs, high level of acceptance by patients and a low rate of dropout. Here, we aimed to analyze all available evidence on the role of Cucurbita pepo in the treatment of LUTS-BPH. MATERIAL AND METHODS: In May 2016 a systematic search was carried out thorough National Library of Medicine Pubmed, Scopus database and the ISI Web of Knowledge official website in order to identify all published studies on Cucurbita pepo and BPH. The following search strings were used: "Cucurbita pepo" OR "pumpkin seed" AND "prostate"; "Cucurbita pepo" AND "antiandrogen" OR "antiproliferative" OR "anti-inflammatory" OR "antioxidant activities"; "cucurbita pepo" OR "pumpkin seed" AND "LUTS" AND "symptoms improvement" OR "quality of life". We consider for the present analysis only studies related to LUTS-BPH. RESULTS: Among all 670 screened, 16 were related to LUTSBPH and finally analyzed. Among all, ten of them were performed in "in vitro setting" showing anti-inflammatory and antiandrogen effect, and a reduction in prostate growth and detrusor activity, while six were clinical studies. In all studies an improvement in International Prostatic Symptoms Score (IPSS) and uroflowmetry parameters has been reported. In 4 studies, an improvement in quality of life has been reported. CONCLUSION: On the basis of our narrative review, the use of Cucurbita pepo in the management of patients affected by LUTS-BPH seems to be useful for improving symptoms and quality of life. However, future clinical trials are requested to confirm these promising results. PMID- 27377092 TI - Robot-assisted laparoscopic resection of a huge pelvic tumor: A case report. AB - The traditional open surgery, for the treatment of huge tumor in the narrow space of pelvic cavity and in close proximity to pelvic organs and neurovascular structures, is very difficult and challenging. We report a case of huge neurilemmoma operated using the robot-assisted laparoscopy. We used interventional pre-operation embolization to control blood supply of tumor because MRI showed the tumor had a sufficient blood supply. PMID- 27377093 TI - Lymphoepithelioma-like carcinoma of the bladder: A case report. AB - type of low differentiated carcinoma of the nasopharyngeal region characterized by marked infiltration of lymphocytes in the area involved by tumor. However, carcinomas with this peculiar morphologic feature have been also described in various anatomic locations and they are generally designated "lymphoepithelioma like carcinomas". Those of the urinary bladder are uncommon as they account of 0.4%-1.3% of all bladder carcinomas. They may coexist with the conventional urothelial carcinoma. Given their rarity, there is poor information regarding their behaviour. Here we present a new case of lymphoepithelioma-like carcinoma in the bladder and we discuss its characteristics and prognosis. PMID- 27377094 TI - Malignant priapism due to penile metastases: Case series and literature review. AB - Malignant priapism secondary to penile metastases is a rare condition. This term was originally used by Peacock in 1938 to describe a condition of painful induration and erection of the penis due to metastatic infiltration by a neoplasm. In the current literature there are 512 case reports. The primary tumor sites are bladder, prostate and rectum. The treatment has only palliative intent and consists of local tumor excision, penectomy, radiotherapy and chemotherapy. We present one case of malignant priapism originated from prostate cancer, and two from urothelial carcinoma of the bladder. Different approaches in diagnosis and therapy were performed. The entire three patient reported a relief of the pain following the treatment, with an improvement of their quality of life, even though it was only temporary as a palliative. Malignant priapism is a rare medical emergency. Penile/pelvis magnetic resonance imaging (MRI) scan and corporal biopsies are considered an effective method of diagnosis of the primary organ site. PMID- 27377095 TI - We really need a classification of prostatic abscess? AB - Not available. PMID- 27377096 TI - Reply to the letter: We really need a classification of prostatic abscess? AB - Not available. PMID- 27377097 TI - Room-Temperature Energy-Sampling Kbeta X-ray Emission Spectroscopy of the Mn4Ca Complex of Photosynthesis Reveals Three Manganese-Centered Oxidation Steps and Suggests a Coordination Change Prior to O2 Formation. AB - In oxygenic photosynthesis, water is oxidized and dioxygen is produced at a Mn4Ca complex bound to the proteins of photosystem II (PSII). Valence and coordination changes in its catalytic S-state cycle are of great interest. In room-temperature (in situ) experiments, time-resolved energy-sampling X-ray emission spectroscopy of the Mn Kbeta1,3 line after laser-flash excitation of PSII membrane particles was applied to characterize the redox transitions in the S-state cycle. The Kbeta1,3 line energies suggest a high-valence configuration of the Mn4Ca complex with Mn(III)3Mn(IV) in S0, Mn(III)2Mn(IV)2 in S1, Mn(III)Mn(IV)3 in S2, and Mn(IV)4 in S3 and, thus, manganese oxidation in each of the three accessible oxidizing transitions of the water-oxidizing complex. There are no indications of formation of a ligand radical, thus rendering partial water oxidation before reaching the S4 state unlikely. The difference spectra of both manganese Kbeta1,3 emission and K-edge X-ray absorption display different shapes for Mn(III) oxidation in the S2 -> S3 transition when compared to Mn(III) oxidation in the S1 -> S2 transition. Comparison to spectra of manganese compounds with known structures and oxidation states and varying metal coordination environments suggests a change in the manganese ligand environment in the S2 -> S3 transition, which could be oxidation of five-coordinated Mn(III) to six-coordinated Mn(IV). Conceivable options for the rearrangement of (substrate) water species and metal ligand bonding patterns at the Mn4Ca complex in the S2 -> S3 transition are discussed. PMID- 27377098 TI - Recurrent Cellulitis Caused by Helicobacter cinaedi in a Patient with X-linked Agammaglobulinaemia. PMID- 27377099 TI - Use of HMUREL Human Coculture System for Prediction of Intrinsic Clearance and Metabolite Formation for Slowly Metabolized Compounds. AB - Design of slowly metabolized compounds is an important goal in many drug discovery projects. Standard hepatocyte suspension intrinsic clearance (CLint) methods can only provide reliable CLint values above 2.5 MUL/min/million cells. A method that permits extended incubation time with maintained performance and metabolic activity of the in vitro system is warranted to allow in vivo clearance predictions and metabolite identification of slowly metabolized drugs. The aim of this study was to evaluate the static HMUREL coculture of human hepatocytes with stromal cells to be set up in-house as a standard method for in vivo clearance prediction and metabolite identification of slowly metabolized drugs. Fourteen low CLint compounds were incubated for 3 days, and seven intermediate to high CLint compounds and a cocktail of cytochrome P450 (P450) marker substrates were incubated for 3 h. In vivo clearance was predicted for 20 compounds applying the regression line approach, and HMUREL coculture predicted the human intrinsic clearance for 45% of the drugs within 2-fold and 70% of the drugs within 3-fold of the clinical values. CLint values as low as 0.3 MUL/min/million hepatocytes were robustly produced, giving 8-fold improved sensitivity of robust low CLint determination, over the cutoff in hepatocyte suspension CLint methods. The CLint values of intermediate to high CLint compounds were at similar levels both in HMUREL coculture and in freshly thawed hepatocytes. In the HMUREL coculture formation rates for five P450-isoform marker reactions, paracetamol (CYP1A2), 1 OH-bupropion (CYP2B6), 4-OH-diclofenac (CYP2C9), and 1-OH-midazolam (3A4) were within the range of literature values for freshly thawed hepatocytes, whereas 1 OH-bufuralol (CYP2D6) formation rate was lower. Further, both phase I and phase II metabolites were detected and an increased number of metabolites were observed in the HMUREL coculture compared to hepatocyte suspension. In conclusion, HMUREL coculture can be applied to accurately estimate intrinsic clearance of slowly metabolized drugs and is now utilized as a standard method for in vivo clearance prediction of such compounds in-house. PMID- 27377100 TI - Theoretical Analysis of Electrochemical Formation and Phase Transition of Oxygenated Adsorbates on Pt(111). AB - The electrochemical oxygenation processes of Pt(111) surface are investigated by combining density functional theory (DFT) calculations and Monto Carlo (MC) simulations. DFT calculations are performed to construct force-field parameters for computing the energy of (?3 * ?3)R30 degrees -structured OH*-H2O* hydrogen bonding networks (differently dissociated water bilayer) on the Pt(111) surface, with which MC simulations are conducted to probe the reversible H2O* <-> OH* conversion in OH*-H2O* networks. The simulated isotherm (relation between electrode potential and OH* coverage) agrees well with that predicted by the experimental cyclic voltammetry (CV) in the potential region of 0.55-0.85 V (vs RHE). It is suggested that the butterfly shape of CV in this region is due to different variation trends of Pt-H2O* distance in low and high OH* coverages. DFT calculation results indicate that the oxidative voltammetry in the potential region from 0.85 V to ca. 1.07 V is associated with the dissociation of OH* to O*, which yields surface structures consisting of OH*-H2O* networks and (?3 * ?3) structured O* clusters. The high stability of the half-dissociated water bilayer (OH*-H2O* hydrogen-bonding network with equal OH* and H2O* coverages) formed in the butterfly region makes OH* dissociation initially very difficult in energetics, but become facile once starts due to the destabilization of OH* by the formed O* nearby. This explains the experimentally observed nucleation and growth behavior of O* phase formation and the high asymmetry of oxidation reduction voltammetry in this potential region. PMID- 27377101 TI - Five lung nodules, four different pathologic findings: not all lung lesions are the same. AB - A patient with a history of colon adenocarcinoma was referred for resection of two lung lesions suspect for metastases. Three additional nodular areas were removed by wedge excision. Pathologic examination revealed four different diagnoses. This particular case demonstrates that the number of lesions may be underestimated on preoperative imaging, even on high-resolution computed tomography and positron emission tomography. Equally, pathologic examination of all detected lesions is vitally important to decide optimal treatment and to determine prognosis. This should be taken into account when discussing alternative treatment options to surgery such as stereotactic radiotherapy and radiofrequency ablation. PMID- 27377102 TI - Location-based technologies for supporting elderly pedestrian in "getting lost" events. AB - PURPOSE: Localization-based technologies promise to keep older adults with dementia safe and support them and their caregivers during getting lost events. This paper summarizes mainly technological contributions to support the target group in these events. Moreover, important aspects of the getting lost phenomenon such as its concept and ethical issues are also briefly addressed. METHODS: Papers were selected from scientific databases and gray literature. Since the topic is still in its infancy, other terms were used to find contributions associated with getting lost e.g. wandering. RESULTS: Trends of applying localization systems were identified as personal locators, perimeter systems and assistance systems. The first system barely considered the older adult's opinion, while assistance systems may involve context awareness to improve the support for both the elderly and the caregiver. Since few studies report multidisciplinary work with a special focus on getting lost, there is not a strong evidence of the real efficiency of localization systems or guidelines to design systems for the target group. CONCLUSIONS: Further research about getting lost is required to obtain insights for developing customizable systems. Moreover, considering conditions of the older adult might increase the impact of developments that combine localization technologies and artificial intelligence techniques. Implications for Rehabilitation Whilst there is no cure for dementia such as Alzheimer's, it is feasible to take advantage of technological developments to somewhat diminish its negative impact. For instance, location-based systems may provide information to early diagnose the Alzheimer's disease by assessing navigational impairments of older adults. Assessing the latest supportive technologies and methodologies may provide insights to adopt strategies to properly manage getting lost events. More user-centered designs will provide appropriate assistance to older adults. Namely, customizable systems could assist older adults in their daily walks with the aim to increase their self-confidence, independence and autonomy. PMID- 27377104 TI - Stem cells, a resource for patients and dentists. PMID- 27377103 TI - Anion Effects in Oxidative Aliphatic Carbon-Carbon Bond Cleavage Reactions of Cu(II) Chlorodiketonate Complexes. AB - Aliphatic oxidative carbon-carbon bond cleavage reactions involving Cu(II) catalysts and O2 as the terminal oxidant are of significant current interest. However, little is currently known regarding how the nature of the Cu(II) catalyst, including the anions present, influence the reaction with O2. In previous work, we found that exposure of the Cu(II) chlorodiketonate complex [(6 Ph2TPA)Cu(PhC(O)CClC(O)Ph)]ClO4 (1) to O2 results in oxidative aliphatic carbon carbon bond cleavage within the diketonate unit, leading to the formation of benzoic acid, benzoic anhydride, benzil, and 1,3-diphenylpropanedione as organic products. Kinetic studies of this reaction revealed a slow induction phase followed by a rapid decay of the absorption features of 1. Notably, the induction phase is not present when the reaction is performed in the presence of a catalytic amount of chloride anion. In the studies presented herein, a combination of spectroscopic (UV-vis, EPR) and density functional theory (DFT) methods have been used to examine the chloride and benzoate ion binding properties of 1 under anaerobic conditions. These studies provide evidence that each anion coordinates in an axial position of the Cu(II) center. DFT studies reveal that the presence of the anion in the Cu(II) coordination sphere decreases the barrier for O2 activation and the formation of a Cu(II)-peroxo species. Notably, the chloride anion more effectively lowers the barrier associated with O O bond cleavage. Thus, the nature of the anion plays an important role in determining the rate of reaction of the diketonate complex with O2. The same type of anion effects were observed in the O2 reactivity of the simple Cu(II) bipyridine complex [(bpy)Cu(PhC(O)C(Cl)C(O)Ph)ClO4] (3). PMID- 27377105 TI - Familial and dietary risk factors in Early Childhood Caries. AB - AIM: To evaluate the causes of Early Childhood Caries. METHODS: STUDY DESIGN: A statistical comparison of two groups of patients, aged between 3 and 6, and their parents, in the 3-year period 2013-2015 was performed. Two groups of patients were selected: 40 children with early childhood caries (ECC group) and 40 children with no decay (controls). Parents were asked to fill out a questionnaire on food habits, oral hygiene habits, fluoride prophylaxis and family history of caries. A dental visit of children and parents was performed (collection of dmft and DMFT index). The saliva features of the two groups of children (concentration of Streptococcus mutans, pH of the oral cavity and buffer capability of stimulated saliva) were examined by means of salivary tests. The distribution of the population was analysed and parametric and non-parametric tests for continuous and non-continuous variables, were used when appropriate. The statistical significance was set at p > 0.005. RESULTS AND STATISTICS: The average age, gender and BMI index of children of the two groups was similar. The difference between the two groups is statistically significant for pH (p=0.000) and buffer capability (p=0.001). The DMFT index in the group of mothers of ECC children is higher compared to the mothers of controls (p=0.004). The comparison among the means, for the parameters connected to the consumption of fruit juice, tea, soft drinks, candies, use of pacifier dipped in sugar or honey and the length (in months) of consumption of candies show statistically significant differences (p>0.05). The pH is higher in those children (24) who never consumed fruit juice, tea, soft drinks before the information received (p<0.05). CONCLUSIONS: Children developing Early Childhood Caries have a diet characterised by high free sugars intake. Diet and, in particular, the consumption of drinks containing free sugars is the most important factor in determining the onset of ECC, being able to affect the oral environment and, in particular, saliva. There is a relationship between maternal and child's oral health, with a DMFT higher in mothers of ECC subjects than in controls' mothers. PMID- 27377106 TI - Aneurismal bone cyst: a conservative surgical technique. A case report treated with a small access osteotomy. AB - BACKGROUND: Aneurismal bone cysts (ABCs) are benign, non-neoplastic, expansive, and locally destructive lesions that may occur rarely. They are well defined and usually occur in the long bones, pelvis and vertebrae. According to the 2005 World Health Organization (WHO) histological classification of odontogenic tumours, ABC is classified as a bone-related lesion as ossyfing fibroma, fibrous dysplasia, osseous dysplasia, central giant cell lesion (granuloma-CGCL), cherubism and simple bone cyst (SBC). ABCs, as CGCLs and SBCs may arise as a consequence of an earlier trauma causing an overflow of blood into the bone, though a number of pathogenic theories have been put forward. The aim of this study is to present an unusual case of aneurismal bone cyst and to compare the different possibilities of surgical treatment after review of the literature. CASE REPORT: ABC was localised in the posterior right region of the mandible in an 11-year-old boy, and removed by a surgical procedure involving a small access osteotomy of the mandibular ramus with removal of the cortical bone in order to enucleate the whole lesion, the wisdom tooth and to preserve the healthy bone. PMID- 27377107 TI - Unusually intruded primary upper incisor: potential threat after 7 years of asymptomatic course. Diagnosis and treatment. AB - BACKGROUND: Misdiagnosis of traumatic injuries can lead to inadequate treatment and complications both in the short and in the long term. Diagnosis and treatment of a patient who underwent an unusual dental trauma to the primary teeth is described. CASE REPORT: A misdiagnosed deeply intruded primary upper central incisor caused massive bleeding after seven years of asymptomatic course. The adequate diagnosis and management of the intrusion and oronasal connection is described. Furthermore, the importance of a thorough dental examination is addressed in the discussion. CONCLUSION: The proper immediate diagnosis and knowledge regarding traumatised mixed dentition is important to reduce the extent of damage and late complications. That is why every child that undergoes head injury should be examined by a dental professional. PMID- 27377108 TI - Indirect pulp capping versus pulpotomy for treating deep carious lesions approaching the pulp in primary teeth: a systematic review. AB - AIM: To assess dental practice regarding the use of indirect pulp capping or pulpotomy in children with deep carious lesions approaching the pulp in primary teeth and to compare the efficacy of the two pulp treatments. METHODS: STUDY DESIGN: Systematic review. We searched the Cochrane Library, PubMed via MEDLINE, and EMBASE as well as the reference lists of included reports and ClinicalTrials.gov (for ongoing trials). Eligible studies were surveys of dental practice sent to dentists regarding the use of indirect pulp capping and pulpotomy in children with deep carious lesions approaching the pulp in primary teeth and any type of clinical study. Two review authors independently extracted data and assessed risk of bias in duplicate. RESULTS: Of the 481 potentially eligible articles, 11 were included in the review: 8 described surveys of dental practice, 1 a non-randomised study, and 2 ongoing randomised trials. The surveys of dental practice showed an overall increase in the teaching and practice of indirect pulp capping in primary teeth. The non- randomised study found a statistically significant difference in favour of indirect pulp capping for clinical and radiological success at 3 years but with high overall risk of bias. CONCLUSIONS: Despite the success rate of indirect pulp capping for treating deep carious lesions approaching the pulp in primary teeth, practitioners still hesitate to practice this technique because of lack of evidence and studies on this topic. Thus, for strong evidence, investigators are encouraged to conduct randomised trials comparing the efficacy of indirect pulp capping and pulpotomy for treating deep carious lesions approaching the pulp in primary teeth. PMID- 27377109 TI - Restorative approaches to treat dentin caries in preschool children: systematic review. AB - AIM: Dental restorations have long been used for the management of early childhood caries, but there is a need to have an evidence based approach when selecting the most appropriate restorative intervention to treat dentin caries in preschool children. This systematic review aimed to assess the effectiveness of restorative treatments of dentin caries in primary teeth in preschool children. MATERIALS AND METHODS: DESIGN: A systematic search of the main electronic databases (Pubmed, Cochrane Collaboration, EMBASE) was conducted to identify peer reviewed papers published in English in the years 1947-2014. Search keywords and MeSH headings were "dental caries", "primary dentition" and "dental restoration". The inclusion criteria were clinical studies conducted in children under 6 years old, and reported findings on the longevity or failure of restorations in primary teeth. Retrieved papers were read by two reviewers independently to assess suitability for inclusion, and the final decision was made by consensus. The quality of the included studies was assessed and data were extracted for analysis. RESULTS: The search identified 348 papers for screening. Among these, 218 papers did not satisfy the study inclusion criteria. Consequently, 130 full papers were retrieved and reviewed. Finally, 9 papers were included. Most of the trials were assessed as having high risk of bias. Five included studies that compared the success rates of restorations with different filling materials and liner materials. Two studies showed clinical advantages of using minimally invasive approaches in caries removal and cavity preparation. The other two trials showed low success rates of interim GI restorations done in a field setting, compared to the high caries arrest rates of silver diammine fluoride application. CONCLUSION: Within the limitation of this systematic review, there is insufficient evidence to make recommendations regarding which material and technique is the most appropriate for restorative treatment in young children. Minimally invasive approaches are advantageous in operative caries management in primary teeth in preschool children. More well-designed randomised controlled trials are required to confirm these findings. PMID- 27377110 TI - Electromyographic evaluation of a patient treated with extraoral traction: a case report. AB - BACKGROUND: This work seeks to provide information on the utility of surface electromyography (SEMG) as an aid for diagnosing orthodontic conditions. Classic orthodontic monitoring by radiography, plaster models, cephalometry, and photography can be improved by using SEMG before and during treatment, to prevent clinical worsening and relapses. CASE REPORT: This paper presents the SEMG results for a 10-year-old female patient, orthodontically treated by extraoral traction (EOT). Significant muscular variations in the patient's EMG were observed as she changed different postures and as headgear device was used. CONCLUSION: SEMG should be performed prior to the orthodontic treatment to assess the neuromuscular patient's pattern, in order to prevent strain induced by extraoral forces. EMG can be a valid aid for evaluating the patient's neuromuscular condition before, during, and after orthodontic treatment. PMID- 27377111 TI - The need for repeated dental care under general anaesthesia in children. AB - AIM: Though the use of advanced behaviour management may facilitate dental treatment in children, some patients still require comprehensive care under general anaesthesia (GA). This is especially true for young children and/or medically compromised children. Thus, this study aimed to provide information about children undergoing GA with regard to age, sex and medical conditions (ICD 10), repeated treatments, dental procedures and recall. MATERIALS AND METHODS: A total of 464 medically compromised children treated under GA in a dental university clinic between 2004 and 2012 were included. Patients' records were analysed retrospectively using SPSS (Version 21.0) and R for statistical analysis. RESULTS: More than 75% of the patients were younger than six years when receiving initial GA. The proportion of children subjected to repeated treatments was low, at 11% for a second and <2% for a third round of GA. The greatest proportion of dental care consisted of restorative therapy and tooth extractions. The recall behaviour observed between the first and second GA revealed no significant influence on the time elapsed in between events (p>0.05). CONCLUSION: Oral care in children with medical conditions is mostly caries-related, and repeated treatment may be necessary, though it was generally uncommon in this university-based study population. PMID- 27377112 TI - Indicators of jawbone asymmetry through analysis of panoramic radiographs. AB - AIM: To assess the degree of jawbone asymmetry by drawing vertical lines on digital panoramic radiographs of paediatric patients with right or left unilateral cross-bite. MATERIALS AND METHODS: STUDY DESIGN: The sample consisted of 217 paediatric patients of both genders, aged 6-9 years. A set of vertical lines was drawn on the side of the mandible with the cross-bite and on the side without the cross-bite, using software program tpsDigs version 2. Subsequently, the differences in the measurements of the two sides were determined through statistical analysis. RESULTS: Analysis of the vertical jaw lines on the radiographic bite indices indicated, in every case, quantifiable differences between the side with the cross-bite and the side without the cross-bite. The differences between vertical variables, related to the heights of the mandible body and the condyle, were statistically significant (p>0.005) for the whole sample and both genders. Statistically significant differences in the heights of the mandible body were found for all the age groups (6 to 9 years old), except for the 9-year-old group, which registered differences in the variables of condylar height. CONCLUSION: Throughout the sample and regardless of the side affected by cross-bite, the vertical variables corresponding to the total height of the ramus were always smaller on the side with the cross-bite. Gender did not affect the results obtained and age influenced some of the mandible's vertical heights. PMID- 27377113 TI - Chloral hydrate for sedation of children with asthma during dental treatment. AB - AIM: We hypothesised that chloral hydrate is safe and effective for sedation during dental treatments for children with mild asthma. We evaluated the safety and efficacy of chloral hydrate by measuring changes in heart rate (HR), transcutaneous oxygen saturation, (SpO2), asthma score, behaviour, types and frequency of adverse reactions associated with chloral hydrate were assessed throughout treatment. MATERIALS AND METHODS: Children (<10 years old) with mild asthma undergoing dental treatments received a single 65 mg/kg oral dose of chloral hydrate liquid 1 hour prior to treatment in an open label trial. Heart rate (HR), SpO2, asthma score, behaviour, types and frequency of adverse reactions associated with chloral hydrate were assessed throughout treatment. Asthma score was obtained before and after treatment. Thirty minutes after treatment, SpO2, HR, and level of consciousness was assessed. RESULTS: Twenty four children were enrolled and 92% (22/24) recovered from sedation without respiratory depression. Two experienced mild respiratory depression related to chloral hydrate. Asthma was not a contributing factor as they did not experience wheezing, cough, tachypnoea, or retractions. Inhaled nitrous oxide supplemented chloral hydrate sedation in 63% (15/24) children to achieve effective cooperation. Three children had a SpO2 <95% (2 during treatment, 1 during recovery). CONCLUSION: Chloral hydrate 65 mg/kg administered a as single oral dose appears to be safe with respect to disease exacerbation for children with mild asthma undergoing dental treatment. Due to ineffective sedation and mild respiratory depression associated with chloral hydrate, newer, easily titrated medications, such as midazolam, may offer advantages. PMID- 27377114 TI - Transverse maxillary deficit and its influence on the cervical vertebrae maturation index. AB - AIM: The aim of this study is to evaluate whether a transverse maxillary deficit can cause an alteration of vertebral development and therefore of the skeletal maturation comparing the cervical maturation stages index with the hand-wrist index. MATERIALS AND METHODS: For the study were selected 200 patients aged 7-14 years, equally distributed by gender and divided into 100 study subjects with maxillary deficit and 100 controls without maxillary deficit. The skeletal maturation index (SM according to Fishman) was evaluated and compared with the hand-wrist x-rays and the cervical vertebrae maturation (CVM according to Hassel and Farmann). RESULTS: Forty-one per cent of the subjects in the test group show a discrepancy between CVM and SM. Among these 73% (30 subjects) present an advanced stage of CVM compared with the corresponding SM. Only 16% of the subjects in the control group show a discrepancy between CVM and SM. Among these 69% (11 subjects) appear in an advanced CVM stage. CONCLUSION: The analysis of the CVM stage in subjects with transverse maxillary deficit appears to be altered compared with the SM identified through a hand-wrist x-ray. In the case of individuals with transverse maxillary deficit it is advisable to use also a hand wrist x-ray, thus not relying only on CVM for the evaluation of the skeletal growth stages. PMID- 27377115 TI - Pain management during needle insertion with low level laser. AB - AIM: To date, there is no safe, effective, and rapid method to eliminate the pain associated with needle insertion. It is noticed that using a low-energy laser before intradermal and intramuscular injection would help rapid local anaesthesia with a lidocaine product. However, there is no valuable data on the effect of the concomitant use of laser and benzocaine as a pre-treatment option, compared to local application of benzocaine products alone before needle insertion. MATERIALS AND METHODS: A prospective single-blind clinical trial was designed to assess pain perception during needle insertion into mucosa in 66 healthy volunteer dental students. They received a topical anaesthetic agent on one side (control) applied for one minute and a topical anaesthetic agent plus low-power laser on the other side (experimental) prior to needle insertion. The first pre-treatment method was chosen based on block randomisation table. A dentist recorded the subjects' reaction based on the visual analogue scale (VAS) during insertion of needle in the two groups. SPSS version 15 was used for data analysis. The statistical significant level was defined at P-value< 0.01. RESULTS: The mean scores of VAS for the experimental and control groups was 21+/- and 19+/- 2.70 respectively, with a statistically significant higher VAS score in the experimental group, although it was not clinically significant. CONCLUSION: Simultaneous application of laser with local anaesthetic products containing benzocaine in the buccal mucosa before dental needle insertion does not reduce pain perception. PMID- 27377116 TI - Palate and alveolar ridge development in predental infants: a longitudinal study. AB - AIM: To investigate the developmental process of palate morphology, including the alveolar ridge, in healthy infants for the predental period of 7 months from immediately after birth. METHODS: The subjects were 32 healthy infants. Four or more dental casts were taken of each subject from immediately after birth until 7 months, for a total of 144 dental casts. Twelve characteristics were then measured in order to morphologically study the subjects' palate development. Principal component analysis (PCA) was performed to investigate morphological changes in the palatal vault. RESULTS: The 12 characteristics were classified into either the alveolar ridge characteristics group, which determined the size of the alveolar ridge, or the palate characteristics group, which determined palate morphology, with each group showing different growth patterns. The characteristics of width and length increased with age in the alveolar ridge characteristics group; this correlation was maintained throughout the predental period. Meanwhile, in the palate characteristics group, the characteristics showed major developmental changes in the first 2 to 3 months after birth, but the changes were subsequently fewer from 3 to 7 months. The PCA of the palatal vault showed that the first principal component increased until 3 months but subsequently ceased to change. CONCLUSIONS: In predental infants, growth patterns of palate morphology differed according to their characteristics. There were major developmental changes in the palate during the first 3 months after birth. The study findings suggest that palate growth in the first half of the predental period may affect subsequent palate growth. PMID- 27377117 TI - Oral manifestations of gastrointestinal diseases in children. Part 2: Crohn's disease. AB - Alterations within the oral cavity can be the first sign of systemic diseases and may thus allow for an early diagnosis and treatment. In particular, being the oral cavity a part of the gastrointestinal system, oral alterations can be an expression of a gastrointestinal disease. Diffuse mucosal swelling, cobblestone mucosa, localised mucogingivitis, deep linear ulceration, fibrous tissue tags, polyps, nodules, pyostomatitis vegetans, and aphthous-like ulcers have been described in Crohn's disease. A prompt recognition of systemic diseases through a careful examination of the oral cavity allows for proper investigations and timely treatment. PMID- 27377118 TI - Management of airway obstruction with nebulised adrenaline resulting in takotsubo cardiomyopathy: case report. AB - BACKGROUND: Takotsubo cardiomyopathy has been associated with the use of catecholamines; however, its development after the use of nebulised adrenaline for the management of acute airway obstruction has not previously been described. CASE REPORT: A 66-year-old man with squamous cell carcinoma of the larynx, with tumour-node-metastasis staging of T3N2cM0, confirmed by biopsy and computed tomography, presented to the emergency department with acute airway obstruction. He was treated twice with nebulised adrenaline and intravenous dexamethasone. After a period of 24 hours, cardiac rhythm changes were noted on telemetry. A 12 lead electrocardiogram showed widespread T-wave inversion and QT prolongation suggestive of an acute coronary syndrome. Coronary angiography demonstrated no coronary artery disease, but left ventricular angiography showed marked apical ballooning and apical wall akinesia consistent with a diagnosis of takotsubo cardiomyopathy. CONCLUSION: Takotsubo cardiomyopathy can mimic true ischaemic heart disease and the diagnosis requires a high index of suspicion in patients managed with nebulised adrenaline. PMID- 27377119 TI - Complex tribomechanical characterization of ZnO nanowires: nanomanipulations supported by FEM simulations. AB - In the present work, we demonstrate a novel approach to nanotribological measurements based on the bending manipulation of hexagonal ZnO nanowires (NWs) in an adjustable half-suspended configuration inside a scanning electron microscope. A pick-and-place manipulation technique was used to control the length of the adhered part of each suspended NW. Static and kinetic friction were found by a 'self-sensing' approach based on the strain profile of the elastically bent NW during manipulation and its Young's modulus, which was separately measured in a three-point bending test with an atomic force microscope. The calculation of static friction from the most bent state was completely reconsidered and a novel more realistic crack-based model was proposed. It was demonstrated that, in contrast to assumptions made in previously published models, interfacial stresses in statically bent NW are highly localized and interfacial strength is comparable to the bending strength of NW measured in respective bending tests. PMID- 27377120 TI - In Vivo Significance of In Vitro Studies on G-Protein-Coupled Receptor Heteromers. PMID- 27377122 TI - Practice manager expectations of new graduate registered nurses in Australian general practice: a national survey. AB - Practice managers are often involved in the employment of practice nurses and are likely to have a significant role in future transition programs in general practice. Therefore, the aim of the study was to explore practice managers' expectations of new graduate registered nurses working in general practice. A nation-wide web-based electronic survey distributed by the Australian Association of Practice Management was used to collect demographic data and practice managers' expectations of new graduate nurses directly transitioning into general practice in their first year of practice. The sample was broadly representative of the Australian state and territory population numbers. Respondents were predominantly female with postgraduate qualifications. The findings of this study highlight that practice managers who currently work with practice nurses would be supportive of graduate registered nurses in general practice in their first year with preceptor support. The results of this study have important implications for nursing workforce development and it is recommended that such initiatives are widely introduced with appropriate financial support. PMID- 27377121 TI - Classical Hodgkin Lymphoma with Positive Epstein-Barr Virus Status is Associated with More FOXP3 Regulatory T Cells. AB - BACKGROUND Classical Hodgkin lymphoma (cHL) is characterized by sparse malignant Hodgkin and Reed-Sternberg cells dispersed in an inflammatory microenvironment. Immune evasion of malignant cells is partially due to the existence of a subpopulation of immunosuppressive regulatory T cells (Treg). The aim of this study was to analyze T cell composition in cHL with special emphasis on Treg in regard to Epstein-Barr virus (EBV) status, subtype, and patient age. MATERIAL AND METHODS The study included 102 patients with cHL diagnosed during a 12-year period. EBV status of cHL was assessed immunohistochemically using antibodies directed to the EBV- encoded LMP1. To define T lymphocyte populations, slides were double-stained with FOXP3 for Treg, and CD4 or CD8 for T cells. In each case the number of single- and/or double-positive cells was counted on an image analyzer in 10 high-power fields. Statistical analysis was performed and differences were considered significant at P<0.05. RESULTS EBV-positive status of cHL was confirmed in 30 (29%) cases, mainly in patients older than 54 years and in mixed cellularity subtype. In EBV-positive cHL, higher numbers of CD8+ cells were found. In cHL with positive EBV status, more FOXP3+ Treg were found, as well as higher numbers of FOXP3+CD4+ Treg compared with EBV-negative cHL. The number of CD4+ cells decreased with age. The frequency of FOXP3+CD8+ Treg was variable, without a statistically significant association with age or EBV status. CONCLUSIONS EBV status has an impact on composition of T cell populations in the cHL microenvironment. PMID- 27377123 TI - A Test-Retest Reliability Study of Human Experimental Models of Histaminergic and Non-histaminergic Itch. AB - Numerous exploratory, proof-of-concept and interventional studies have used histaminergic and non-histaminergic human models of itch. However, no reliability studies for such surrogate models have been conducted. This study investigated the test-retest reliability for the response to histamine- and cowhage- (5, 15, 25 spiculae) induced itch in healthy volunteers. Cowhage spiculae were individually applied with tweezers and 1% histamine was applied with a skin prick test (SPT) lancet, both on the volar forearm. The intensity of itch was recorded on a visual analogue scale and self-reported area of itch was assessed 5 and 10 min after itch provocation. Reliability of the evoked itch (area under the curve and peak intensity) was assessed by the coefficient of variation (CV), intra class correlation coefficient (ICC), and sample size estimation for parallel and cross-over designs. Cowhage (ICC = 0.57-0.77, CVbetween = 97%, CVwithin = 41%) and histamine: (ICC = 0.83-0.93, CVbetween = 97%, CVwithin = 20%) exhibited moderate-to-excellent intra-individual reliability and moderate inter-individual reliability for the itch intensity. For a test-retest observation period of one week, SPT-delivered histamine and application of cowhage-spiculae are reproducible human models of itch. The high inter-individual and low intra individual variability suggests cross-over designed studies when applicable. PMID- 27377124 TI - In-Depth Characterization of a Pro-Antibody-Drug Conjugate by LC-MS. AB - Pro-antibody-drug conjugate (PDC) is a hybrid structural format of immunoconjugate, where the structural complexity of pro-antibody and intrinsic heterogeneity of ADCs impose a prominent analytical challenge to the in-depth characterization of PDCs. In the present study, we successfully prepared and characterized PanP-DM1 as a model of PDCs, which is an anti-EGFR pro-antibody following conjugation with DM1 at lysine residues. The drug-to-antibody ratio (DAR) of PanP-DM1 was determined by LC-MS after deglycosylation, and verified by UV/vis spectroscopy. Following reduction or IdeS digestion, the pro-antibody fragments linked with DM1 were investigated by middle-down mass spectrometry. Furthermore, more than 20 modified lysine conjugation sites were determined by peptide mapping after trypsin digestion. Additionally, more than ten glycoforms of PanP-DM1 were also identified and quantified. In summary, critical quality attributes (CQAs) of PDCs including DAR, drug load distribution, and conjugation sites were fully characterized, which would contribute to the development of other PDCs for cancer treatment. PMID- 27377125 TI - Direct Chemical Synthesis of MnO2 Nanowhiskers on Transition-Metal Carbide Surfaces for Supercapacitor Applications. AB - Transition-metal carbides (MXenes) are an emerging class of two-dimensional materials with promising electrochemical energy storage performance. Herein, for the first time, by direct chemical synthesis, nanocrystalline epsilon-MnO2 whiskers were formed on MXene nanosheet surfaces (epsilon-MnO2/Ti2CTx and epsilon MnO2/Ti3C2Tx) to make nanocomposite electrodes for aqueous pseudocapacitors. The epsilon-MnO2 nanowhiskers increase the surface area of the composite electrode and enhance the specific capacitance by nearly 3 orders of magnitude compared to that of pure MXene-based symmetric supercapacitors. Combined with enhanced pseudocapacitance, the fabricated epsilon-MnO2/MXene supercapacitors exhibited excellent cycling stability with ~88% of the initial specific capacitance retained after 10000 cycles which is much higher than pure epsilon-MnO2-based supercapacitors (~74%). The proposed electrode structure capitalizes on the high specific capacitance of MnO2 and the ability of MXenes to improve conductivity and cycling stability. PMID- 27377126 TI - A compact tunable polarized X-ray source based on laser-plasma helical undulators. AB - Laser wakefield accelerators have great potential as the basis for next generation compact radiation sources because of their extremely high accelerating gradients. However, X-ray radiation from such devices still lacks tunability, especially of the intensity and polarization distributions. Here we propose a tunable polarized radiation source based on a helical plasma undulator in a plasma channel guided wakefield accelerator. When a laser pulse is initially incident with a skew angle relative to the channel axis, the laser and accelerated electrons experience collective spiral motions, which leads to elliptically polarized synchrotron-like radiation with flexible tunability on radiation intensity, spectra and polarization. We demonstrate that a radiation source with millimeter size and peak brilliance of 2 * 10(19) photons/s/mm(2)/mrad(2)/0.1% bandwidth can be made with moderate laser and electron beam parameters. This brilliance is comparable with third generation synchrotron radiation facilities running at similar photon energies, suggesting that laser plasma based radiation sources are promising for advanced applications. PMID- 27377127 TI - Role of Epigenetics in Biology and Human Diseases. AB - For a long time, scientists have tried to describe disorders just by genetic or environmental factors. However, the role of epigenetics in human diseases has been considered from a half of century ago. In the last decade, this subject has attracted many interests, especially in complicated disorders such as behavior plasticity, memory, cancer, autoimmune disease, and addiction as well as neurodegenerative and psychological disorders. This review first explains the history and classification of epigenetic modifications, and then the role of epigenetic in biology and connection between the epigenetics and environment are explained. Furthermore, the role of epigenetics in human diseases is considered by focusing on some diseases with some complicated features, and at the end, we have given the future perspective of this field. The present review article provides concepts with some examples to reveal a broad view of different aspects of epigenetics in biology and human diseases. PMID- 27377128 TI - RIP3 induces ischemic neuronal DNA degradation and programmed necrosis in rat via AIF. AB - We have reported that nuclear translocation of Receptor-interacting protein 3 (RIP3) involves in neuronal programmed necrosis after 20-min global cerebral ischemia/reperfusion (I/R) injury. Herein, the underlying mechanisms and the nuclear role of RIP3 were investigated further. The necroptosis inhibitor necrostatin-1 (Nec-1), the autophagy inhibitor 3-methyladenine (3-MA), and the caspase-3 inhibitor acetyl-L-aspartyl-L-methionyl-L-glutaminyl-L-aspart-1-al (Ac DMQD-CHO) were administered intracerebroventricularly 1 h before ischemia. Protein expression, location and interaction was determined by western blot, immunofluorescence or immunoprecipitation. Most CA1 neuronal death induced by 20 min global cerebral I/R injury was TUNEL-positive. Neuronal death and rat mortality rates were greatly inhibited by Nec-1 and 3-MA pre-treatment, but not by Ac-DMQD-CHO. And no activation of caspase-3 was detected after I/R injury. Caspase-8 was expressed richly in GFAP-positive astrocytes and Iba-1-positive microglia, but was not detected in Neun-positive neurons. The nuclear translocation and co-localization of RIP3 and AIF, and their interaction were detected after I/R injury. These processes were inhibited by Nec-1 and 3-MA pre treatment, but not by Ac-DMQD-CHO. The formation of an RIP3-AIF complex and its nuclear translocation are critical to ischemic neuronal DNA degradation and programmed necrosis. Neurons are more likely to enter the programmed necrosis signal pathway for the loss of caspase-8 suppression. PMID- 27377129 TI - Conformational stability of digestion-resistant peptides of peanut conglutins reveals the molecular basis of their allergenicity. AB - Conglutins represent the major peanut allergens and are renowned for their resistance to gastro-intestinal digestion. Our aim was to characterize the digestion-resistant peptides (DRPs) of conglutins by biochemical and biophysical methods followed by a molecular dynamics simulation in order to better understand the molecular basis of food protein allergenicity. We have mapped proteolysis sites at the N- and C-termini and at a limited internal segment, while other potential proteolysis sites remained unaffected. Molecular dynamics simulation showed that proteolysis only occurred in the vibrant regions of the proteins. DRPs appeared to be conformationally stable as intact conglutins. Also, the overall secondary structure and IgE-binding potency of DRPs was comparable to that of intact conglutins. The stability of conglutins toward gastro-intestinal digestion, combined with the conformational stability of the resulting DRPs provide conditions for optimal exposure to the intestinal immune system, providing an explanation for the extraordinary allergenicity of peanut conglutins. PMID- 27377130 TI - Simultaneous SPECT imaging of multi-targets to assist in identifying hepatic lesions. AB - Molecular imaging technique is an attractive tool to detect liver disease at early stage. This study aims to develop a simultaneous dual-isotope single photon emission computed tomography (SPECT)/CT imaging method to assist diagnosis of hepatic tumor and liver fibrosis. Animal models of liver fibrosis and orthotopic human hepatocellular carcinoma (HCC) were established. The tracers of (131)I-NGA and (99m)Tc-3P-RGD2 were selected to target asialoglycoprotein receptor (ASGPR) on the hepatocytes and integrin alphavbeta3 receptor in tumor or fibrotic liver, respectively. SPECT imaging and biodistribution study were carried out to verify the feasibility and superiority. As expected, (99m)Tc-3P-RGD2 had the ability to evaluate liver fibrosis and detect tumor lesions. (131)I-NGA showed that it was effective in assessing the anatomy and function of the liver. In synchronized dual-isotope SPECT/CT imaging, clear fusion images can be got within 30 minutes for diagnosing liver fibrosis and liver cancer. This new developed imaging approach enables the acquisition of different physiological information for diagnosing liver fibrosis, liver cancer and evaluating residual functional liver volume simultaneously. So synchronized dual-isotope SPECT/CT imaging with (99m)Tc 3P-RGD2 and (131)I-NGA is an effective approach to detect liver disease, especially liver fibrosis and liver cancer. PMID- 27377131 TI - Effectiveness of iPad apps on visual-motor skills among children with special needs between 4y0m-7y11m. AB - AIMS: The aim of this randomized controlled trial was to assess the effectiveness of interventions using iPad applications compared to traditional occupational therapy on visual-motor integration (VMI) in school-aged children with poor VMI skills. METHODS: Twenty children aged 4y0m to 7y11m with poor VMI skills were randomly assigned to the experimental group (interventions using iPad apps targeting VMI skills) or control group (traditional occupational therapy intervention sessions targeting VMI skills). The intervention phase consisted of two 40-min sessions per week, over a period of 10 weeks. Participants were required to attend a minimum of 8 and a maximum of 12 sessions. The subjects were tested using the Beery-VMI and the visual-motor subscale of the M-FUN, at baseline and follow-up. RESULTS: Results from a 2-way mixed design ANOVA yielded significant results for the main effect of time for the M-FUN total raw score, as well as in the subscales Amazing Mazes, Hidden Forks, Go Fishing and VM Behavior. However, gains did not differ between intervention types over time. No significant results were found for the Beery-VMI. CONCLUSIONS: This study supports the need for further research into the use of iPads for the development of VMI skills in the pediatric population. Implications for Rehabilitation This is the first study to look at the use of iPads with school-aged children with poor visual-motor skills. There is limited literature related to the use of iPads in pediatric occupational therapy, while they are increasingly being used in practice. When compared to the traditional occupational therapy interventions, participants in the iPad intervention appeared to be more interested, engaged and motivated to participate in the therapy sessions. Using iPad apps as an adjunct to therapy in intervention could be effective in improving VMI skills over time. PMID- 27377133 TI - Colorectal cancer: CpG island methylation indicates inferior survival outcomes. PMID- 27377132 TI - Combine and conquer: challenges for targeted therapy combinations in early phase trials. AB - Our increasing understanding of cancer biology has led to the development of molecularly targeted anticancer drugs. The full potential of these agents has not, however, been realised, owing to the presence of de novo (intrinsic) resistance, often resulting from compensatory signalling pathways, or the development of acquired resistance in cancer cells via clonal evolution under the selective pressures of treatment. Combinations of targeted treatments can circumvent some mechanisms of resistance to yield a clinical benefit. We explore the challenges in identifying the best drug combinations and the best combination strategies, as well as the complexities of delivering these treatments to patients. Recognizing treatment-induced toxicity and the inability to use continuous pharmacodynamically effective doses of many targeted treatments necessitates creative intermittent scheduling. Serial tumour profiling and the use of parallel co-clinical trials can contribute to understanding mechanisms of resistance, and will guide the development of adaptive clinical trial designs that can accommodate hypothesis testing, in order to realize the full potential of combination therapies. PMID- 27377134 TI - An Amphiphilic Peptide Induces Apoptosis Through the miR29b-p53 Pathway in Cancer Cells. AB - Peptides have been in the limelight, as therapeutic agents for cancer treatment through various applications due to their high target selectivity and exceptional ability to penetrate the cell membrane. Recent studies have revealed that synthesized peptides bind to hairpin structures of RNA that affect their activities such as changing the efficacy of microRNA maturation. MicroRNA mediated p53 activation by the microRNA-29 (miR29) family is one of the most important regulatory pathways in cancer therapeutics. By targeting the suppressors of p53, a tumor suppressor protein, miR29 induces apoptosis of cancer cells through p53 stabilization. Here, we identify a novel synthesized amphiphilic peptide, LK-L1C/K6W/L8C, which enhances expression of miR29b and promotes p53 activity. In the presence of LK-L1C/K6W/L8C, pre-miR29b preferentially forms a complex with the Dicer protein through interaction of LK L1C/K6W/L8C with the terminal loop region of pre-miR29b, leading to an increase in Dicer processing. Furthermore, LK-L1C/K6W/L8C stimulates apoptosis by improving p53 stability in miR29-inducible HeLa and MCF7 cells. Collectively, our study shows that a peptide can directly influence the miR29b-mediated p53 activation pathway in cancer cells. Therefore, our findings provide the basis for a new, potentially promising peptide-based drug for cancer therapy. PMID- 27377135 TI - Altered Levels of MicroRNA-9, -206, and -132 in Spinal Muscular Atrophy and Their Response to Antisense Oligonucleotide Therapy. AB - The identification of noninvasive biomarkers to monitor the disease progression in spinal muscular atrophy (SMA) is becoming increasingly important. MicroRNAs (miRNAs) regulate gene expression and are implicated in the pathogenesis of neuromuscular diseases, including motor neuron degeneration. In this study, we selectively characterized the expression of miR-9, miR-206, and miR-132 in spinal cord, skeletal muscle, and serum from SMA transgenic mice, and in serum from SMA patients. A systematic analysis of miRNA expression was conducted in SMA mice with different disease severities (severe type I-like and mild type III-like) at different disease stages (pre-, mid-, and late-symptomatic stages), and in morpholino antisense oligonucleotide-treated mice. There was differential expression of all three miRNAs in spinal cord, skeletal muscle and serum samples in SMA mice. Serum miRNAs were altered prior to the changes in spinal cord and skeletal muscle at the presymptomatic stage. The altered miR-132 levels in spinal cord, muscle, and serum transiently reversed to normal level after a single-dose morpholino antisense oligomer PMO25 treatment in SMA mice. We also confirmed a significant alteration of miR-9 and miR-132 level in serum samples from SMA patients. Our study indicates the potential of developing miRNAs as noninvasive biomarkers in SMA. PMID- 27377136 TI - A group-enhanced sprint interval training program for amateur athletes. AB - Sprint interval training (SIT) can elicit improvements in aerobic and anaerobic capacity. While variations in SIT protocols have been investigated, the influence of social processes cannot be overlooked. As research supports the use of groups to influence individual cognitions and behaviours, the current project assessed the effectiveness of a group-based intervention with participants conducting SIT. Specifically, 53 amateur athletes (age, 21.9 +/- 2.9 years; 53% females) took part in a 4-week training program (3 sessions per week, 30-s "all-out" efforts with 4 min active recovery, repeated 4-6 times per session), and were assigned to "true group", aggregate, or individual conditions. Results indicated no significant differences between groups for the physiological measures. With regards to training improvements from baseline for all participants- regardless of condition - significant main effects for time were identified for maximal oxygen uptake (2.5-2.8 mL.kg(-1).min(-1), p < 0.001, eta(2) = 0.03), time-trial performance (14-32 s, p < 0.001, eta(2) = 0.37), and anaerobic power (1.1-1.7 k.h(-1), p < 0.001, eta(2) = 0.66). With regards to the psychological measures, significant main effects between groups were found for motivation (p = 0.033, eta(2) = 0.13), task self-efficacy (p = 0.018, eta(2) = 0.15), and scheduling self-efficacy (p = 0.003, eta(2) = 0.22). The true group experienced greater improvements in motivation than the individual condition, but the aggregate and individual conditions demonstrated greater increases in task and scheduling self efficacy. Though the SIT paradigm employed induced training improvements similar to previous work, the group intervention was not able to further these improvements. PMID- 27377138 TI - Upcoming Changes for Inorganic Chemistry: Adding Titles to References and Adjusting Communication Length Requirements. PMID- 27377137 TI - Interleukin-6 and associated cytokine responses to an acute bout of high intensity interval exercise: the effect of exercise intensity and volume. AB - Acute increases in interleukin (IL)-6 following prolonged exercise are associated with the induction of a transient anti-inflammatory state (e.g., increases in IL 10) that is partly responsible for the health benefits of regular exercise. The purposes of this study were to investigate the IL-6-related inflammatory response to high-intensity interval exercise (HIIE) and to determine the impact of exercise intensity and volume on this response. Ten participants (5 males and 5 females) completed 3 exercise bouts of contrasting intensity and volume (LOW, MOD, and HIGH). The HIGH protocol was based upon standard HIIE protocols, while the MOD and LOW protocols were designed to enable a comparison of exercise intensity and volume with a fixed duration. Inflammatory cytokine concentrations were measured in plasma (IL-6, IL-10) and also determined the level of gene expression (IL-6, IL-10, and IL-4R) in peripheral blood. The plasma IL-6 response to exercise (reported as fold changes) was significantly greater in HIGH (2.70 +/ 1.51) than LOW (1.40 +/- 0.32) (P = 0.04) and was also positively correlated to the mean exercise oxygen uptake (r = 0.54, P < 0.01). However, there was no change in anti-inflammatory IL-10 or IL-4R responses in plasma or at the level of gene expression. HIIE caused a significant increase in IL-6 and was greater than that seen in low-intensity exercise of the same duration. The increases in IL-6 were relatively small in magnitude, and appear to have been insufficient to induce the acute systemic anti-inflammatory effects, which are evident following longer duration exercise. PMID- 27377139 TI - Screening for arteriovenous malformations in hereditary haemorrhagic telangiectasia. AB - OBJECTIVE: To determine whether patients with hereditary haemorrhagic telangiectasia were being screened according to international guidelines, and to review recent evidence in order to provide up-to-date guidelines for the initial systemic management of hereditary haemorrhagic telangiectasia. METHODS: A retrospective case note analysis was conducted, assessing patients in terms of screening for: genetics, cerebral arteriovenous malformations, pulmonary and hepatic arteriovenous malformations, and gastrointestinal telangiectasia. Databases searched included Medline, the Cumulative Index to Nursing and Allied Health Literature, and Embase. RESULTS: Screening investigations were most frequently performed for hepatic arteriovenous malformations and least frequently for genetics. Recent data suggest avoiding routine genetic and cerebral arteriovenous malformation screening because of treatment morbidities; performing high-resolution chest computed tomography for pulmonary arteriovenous malformation screening; using capsule endoscopy (if possible) to reduce complications from upper gastrointestinal endoscopy; and omitting routine liver enzyme testing in favour of Doppler ultrasound. CONCLUSION: Opportunities for systemic arteriovenous malformation screening are frequently overlooked. This review highlights the need for screening and considers the form in which it should be undertaken. PMID- 27377140 TI - Satellitosis and CD117 immunohistochemical expression correlates with poor outcome in thick vulvar melanoma. AB - BACKGROUND: Melanoma of the vulva is the second most common vulvar cancer after epidermoid carcinoma. Patients suffering from this disease usually present with a late-stage disease with a poor prognosis. The prognostic factors reported in previous studies are not homogeneous and the clinical/pathogenic role of c-KIT expression is not clear. Breslow staging currently is the most accurate predictor factor. METHODS: A clinicopathological study with literature review was performed to identify predictors of prognosis and survival in melanoma of the vulva and investigated the expression of c-KIT (by immunohistochemistry) in 10 patients from the National Institute for Cancer Research (Mexico City). RESULTS: The 10 patients enrolled were all older women with delayed presentation, high-stage disease and limited response to treatment. Five patients (50%) were found to have c-KIT expression; 4 of them recurred (P=0.01), and ultimately 3 died (P=0.038). We identified satellitosis and c-KIT expression as prognostic predictors for death. CONCLUSIONS: We conclude that c-KIT expression is a valuable predictor of prognosis and survival, especially in thick (>4 mm) melanomas. PMID- 27377141 TI - Efficacy and tolerability of a spray product containing hydroxypropyl chitosan, climbazole and piroctone olamine, applied twice weekly for the treatment of the pitiriasis versicolor. AB - BACKGROUND: The aim of this study was to demonstrate the effectiveness of a product containing hydroxypropyl chitosan, climbazole and piroctone olamine, by monitoring the adherence and the penetration of the molecules in the skin. Confocal microscopy led us to show the persistence of the active compound for a long time in the stratum corneum, thanks to the presence of hydroxypropyl chitosan. This evidence suggests a new protocol of application (a biweekly application, rather than daily). METHODS: Thirty patients (17 males, 13 females; average age 20.8 years) were selected from 3 dermatological centers: the Dermatological Clinic of "Federico II" University of Naples; the Dermatological outpatient clinic of Bologna private hospital "Villa Nigrisoli"; the Section of Cutaneous Appendages of the European Dermatological Institute of Milan. The study protocol entailed application of a topical spray product 2 evenings a week for 2 months. Confocal microscopy, dermoscopy and photographic documentation were performed at the moment of diagnosis (T0), 12 hours after the first application (T1), after 7 days (T2), after 1 month (T3) and after 2 months (T4). RESULTS: The improvements of clinical symptoms were documented by dermoscopy and digital photos. Confocal microscopy shows the persistence of the product in the stratum corneum, at different times of observations. CONCLUSIONS: A biweekly application of a product containing hydroxypropyl chitosan, climbazole and piroctone olamine shows a clinical significative improvement, evaluated through digital photographs and dermoscopic images, with complete resolution at T4 in 100% of cases. PMID- 27377142 TI - Electrochemotherapy for basocellular and squamocellular head and neck cancer: preliminary experience in Day Surgery Unit. AB - BACKGROUND: The aim of this study was to evaluate feasibility, safety and efficacy in day surgery of electrochemotherapy (ECT) using bleomycin in non melanoma head and neck skin cancer. METHODS: We performed a prospective study on fifteen patients treated at the General Surgery Department at University Hospital of Tor Vergata, Rome between April 2011 and February 2013. RESULTS: We observed 100% complete response evaluated with WHO criteria at 6 weeks after treatment. No partial response was achieved. CONCLUSIONS: ECT is a simple, highly effective and safe treatment for head and neck non melanoma skin cancer. In our experience ECT can be performed safely in Day Surgery also in patients ASA III. Side effects associated with ECT are minimal and the treatment is well tolerated also by older patients, with minimal impairment of organ function and healthy tissues and with good esthetic results. We would encourage this treatment especially for older patients with multiple comorbidities, in which conventional surgical approach is not easily practicable. PMID- 27377143 TI - Vibrational and mechanical properties of single layer MXene structures: a first principles investigation. AB - MXenes, carbides, nitrides and carbonitrides of early transition metals are the new members of two dimensional materials family given with a formula of [Formula: see text] X n . Recent advances in chemical exfoliation and CVD growth of these crystals together with their promising performance in electrochemical energy storage systems have triggered the interest in these two dimensional structures. In this work, we employ first principles calculations for n = 1 structures of Sc, Ti, Zr, Mo and Hf pristine MXenes and their fully surface terminated forms with F and O. We systematically investigated the dynamical and mechanical stability of both pristine and fully terminated MXene structures to determine the possible MXene candidates for experimental realization. In conjunction with an extensive stability analysis, we report Raman and infrared active mode frequencies for the first time, providing indispensable information for the experimental elaboration of MXene field. After determining dynamically stable MXenes, we provide their phonon dispersion relations, electronic and mechanical properties. PMID- 27377144 TI - Normal Skin Microbiota is Altered in Pre-clinical Hidradenitis Suppurativa. AB - Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease defined by recurrent nodules, tunnels (sinus tracts) and scarring involving the intertriginous regions. The clinical course of HS is compatible with a biofilm driven disease, and biofilm has been described in lesional HS skin. We therefore hypothesized that clinically unaffected HS skin would also have an increased presence of biofilm compared with that of healthy controls. We conducted a case control study, investigating the morphology of the axillary skin microbiota. Peptide nucleic acid - fluorescence in situ hybridization probes were used in combination with confocal laser scanning microscopy. Significant differences were found in both distribution and quantity of the cutaneous microbiota in clinically non-affected axillary skin of patients with HS compared with healthy controls. Surprisingly, we detected fewer bacteria and less biofilm in patients with HS. The reduced microbiota in patients with HS may play an important role in the early course of the disease. PMID- 27377145 TI - Laser Crystallization of Organic-Inorganic Hybrid Perovskite Solar Cells. AB - Organic-inorganic hybrid perovskites attract enormous research interest for next generation solar energy harvest. Synergistic crystalline structures comprising organic and inorganic components enable solution processing of perovskite films. A reliable crystallization method for perovskites, compatible with fast continuous process over large-area flexible substrates, is crucial for high performance solar cell production. Here, we present laser crystallization of hybrid perovskite solar cells using near-infrared (NIR) laser (lambda = 1064 nm). Crystalline morphology of CH3NH3PbI3 (MAPbI3) perovskite films are widely controllable with laser irradiation condition while maintaining film uniformity. Photothermal heating effectively assisted by interfacial photoconversion layers is critical for phase transformation without beam damage of multilayered device structures. Notably, laser crystallization attains higher device performances than conventional thermal annealing. Fast laser crystallization with manufacture level scan rate (1 m min(-1)) demonstrates inverted-type perovskite solar cells with 11.3 and 8.0% efficiencies on typical glass and flexible polymer substrates, respectively, without rigorous device optimization. PMID- 27377146 TI - Nano-Self-Assemblies Based on Synthetic Analogues of Mycobacterial Monomycoloyl Glycerol and DDA: Supramolecular Structure and Adjuvant Efficacy. AB - The mycobacterial cell-wall lipid monomycoloyl glycerol (MMG) is a potent immunostimulator, and cationic liposomes composed of a shorter synthetic analogue (MMG-1) and dimethyldioctadecylammonium (DDA) bromide represent a promising adjuvant that induces strong antigen-specific Th1 and Th17 responses. In the present study, we investigated the supramolecular structure and in vivo adjuvant activity of dispersions based on binary mixtures of DDA and an array of synthetic MMG-1 analogues (MMG-2/3/5/6) displaying longer (MMG-2) or shorter (MMG-3) alkyl chain lengths, or variations in stereochemistry of the polar headgroup (MMG-5) or of the hydrophobic moiety (MMG-6). Synchrotron small-angle X-ray scattering experiments and cryo transmission electron microscopy revealed that DDA:MMG 1/2/5/6 dispersions consisted of unilamellar and multilamellar vesicles (ULVs/MLVs), whereas a coexistence of both ULVs and hexosomes was observed for DDA:MMG-3, depending on the DDA:MMG molar ratio. The studies also showed that ULVs were formed, regardless of the structural characteristics of the neat MMG analogues in excess buffer [lamellar (MMG-1/2/5) or inverse hexagonal (MMG-3/6) phases]. Immunization of mice with a chlamydia antigen surface-adsorbed to DDA:MMG-1/3/6 dispersions revealed that all tested adjuvants were immunoactive and induced strong Th1 and Th17 responses with a potential for a central effector memory profile. The MMG-1 and MMG-6 analogues were equally immunoactive in vivo upon incorporation into DDA liposomes, despite the reported highly different immunostimulatory properties of the neat analogues in vitro, which were attributed to the different nanostructural characteristics. This clearly demonstrates that optimal formulation and delivery of MMG analogues to the immune system is of major importance and challenges the use of in vitro screening assays with nondispersed compounds to identify potential new vaccine adjuvants. PMID- 27377148 TI - Assessing the uptake and effectiveness of a quick reference guide to antibiotic prescribing in Australian general practice. AB - Prescribing guidelines are an essential component of antimicrobial stewardship programs in Australian hospitals. Nonetheless, the majority of antibiotic prescribing occurs in the community and the effectiveness of guidelines developed specifically to meet the needs of Australian general practice is unknown. This study aims to assess the uptake and effectiveness of a quick reference guide to antibiotic prescribing among primary care prescribers. A quick reference guide to antibiotic prescribing was developed and prescribers in five Tasmanian practices were surveyed regarding use of this guide. Thirty-three surveys were returned and, of those answering specific sections, 75% were aware of the guide and 71% had used it within the last month. The guide affected the antibiotic prescribing practice of 74% of responding prescribers; most often on choice of antibiotic; but also on duration of treatment, dose and dosing frequency. A quick reference guide to antibiotic prescribing was well received by prescribers and may usefully support efforts to improve antimicrobial stewardship in the community. PMID- 27377147 TI - Structural and Magnetic Properties of LaCoO3/SrTiO3 Multilayers. AB - Structural and magnetic properties of the LaCoO3/SrTiO3 (LCO/STO) multilayers (MLs) with a fixed STO layer of 4 nm but varied LCO layer thicknesses have been systematically studied. The MLs grown on Sr0.7La0.3Al0.65Ta0.35O3 (LSAT) and SrTiO3 (STO) exhibit the in-plane lattice constant of the substrates, but those on LaAlO3 (LAO) show the in-plane lattice constant between those of the first two kinds of MLs. Compared with the LCO single layer (SL), the magnetic order of the MLs is significantly enhanced, as demonstrated by a very slow decrease, which is fast for the SL, of the Curie temperature and the saturation magnetization as the LCO layer thickness decreases. For example, clear ferromagnetic order is observed in the ML with the LCO layer of ~1.5 nm, whereas it vanishes below ~6 nm for the LCO SL. This result is consistent with the observation that the dark stripes, which are believed to be closely related to the magnetic order, remain clear in the MLs while they are vague in the corresponding LCO SL. The present work suggests a novel route to tune the magnetism of perovskite oxide films. PMID- 27377149 TI - Exotic skyrmion crystals in chiral magnets with compass anisotropy. AB - The compass-type anisotropy appears naturally in diverse physical contexts with strong spin-orbit coupling (SOC) such as transition metal oxides and cold atomic gases etc, and it has been receiving substantial attention. Motivated by recent studies and particularly recent experimental observations on helimagnet MnGe, we investigate the critical roles of this compass-type anisotropy in modulating various spin textures of chiral magnets with strong SOC, by Monte Carlo simulations based on a classical Heisenberg spin model with Dzyaloshinsky-Moriya interaction and compass anisotropy. A phase diagram with emergent spin orders in the space of compass anisotropy and out-of-plane magnetic field is presented. In this phase diagram, we propose that a hybrid super-crystal structure consisting of alternating half-skyrmion and half-anti-skyrmion is the possible zero-field ground state of MnGe. The simulated evolution of the spin structure driven by magnetic field is in good accordance with experimental observations on MnGe. Therefore, this Heisenberg spin model successfully captures the main physics responsible for the magnetic structures in MnGe, and the present work may also be instructive to research on the magnetic states in other systems with strong SOC. PMID- 27377150 TI - Assessment of upscaling potential of alternative adsorbent materials for highway stormwater treatment in cold climates. AB - Generally, studies on alternative adsorbents focus on adsorbent removal capacity, as a function of pollutant concentration, and other practical aspects, such as costs, environmental impact and end of life costs, that can affect the upscaling of adsorbents for real-life applications, are not explicitly considered. Therefore, this study combines multi-criteria modeling with experimental evaluation to integrate both technical and non-technical factors in assessing the upscaling potential of alternative adsorbents. The experimental step was used to verify the reported pollutant removal as well as testing environmental stability, of the alternative adsorbents, in cold climates. Important factors/criteria for the upscaling process were identified with the help of principal component analysis. The results indicated that adsorbents such as pine bark, olivine and charcoal were the best available options for upscaling. The statistical analysis revealed that factors such as initial costs, hydraulic loads and end-of-life costs were important for the upscaling process and, therefore, should be explicitly included in any future evaluation of the alternative adsorbents. PMID- 27377151 TI - An Eye on Animacy and Intention. PMID- 27377152 TI - Micro-motors: A motile bacteria based system for liposome cargo transport. AB - Biological micro-motors (microorganisms) have potential applications in energy utilization and nanotechnology. However, harnessing the power generated by such motors to execute desired work is extremely difficult. Here, we employ the power of motile bacteria to transport small, large, and giant unilamellar vesicles (SUVs, LUVs, and GUVs). Furthermore, we demonstrate bacteria-bilayer interactions by probing glycolipids inside the model membrane scaffold. Fluorescence Resonance Energy Transfer (FRET) spectroscopic and microscopic methods were utilized for understanding these interactions. We found that motile bacteria could successfully propel SUVs and LUVs with a velocity of 28 MUm s(-1) and 13 MUm s( 1), respectively. GUVs, however, displayed Brownian motion and could not be propelled by attached bacteria. Bacterial velocity decreased with the larger loaded cargo, which agrees with our calculations of loaded bacteria swimming at low Reynolds number. PMID- 27377153 TI - Paper-based microreactor array for rapid screening of cell signaling cascades. AB - Investigation of cell signaling pathways is important for the study of pathogenesis of cancer. However, the related operations used in these studies are time consuming and labor intensive. Thus, the development of effective therapeutic strategies may be hampered. In this work, gel-free cell culture and subsequent immunoassay has been successfully integrated and conducted in a paper based microreactor array. Study of the activation level of different kinases of cells stimulated by different conditions, i.e., IL-6 stimulation, starvation, and hypoxia, was demonstrated. Moreover, rapid screening of cell signaling cascades after the stimulations of HGF, doxorubicin, and UVB irradiation was respectively conducted to simultaneously screen 40 kinases and transcription factors. Activation of multi-signaling pathways could be identified and the correlation between signaling pathways was discussed to provide further information to investigate the entire signaling network. The present technique integrates most of the tedious operations using a single paper substrate, reduces sample and reagent consumption, and shortens the time required by the entire process. Therefore, it provides a first-tier rapid screening tool for the study of complicated signaling cascades. It is expected that the technique can be developed for routine protocol in conventional biological research laboratories. PMID- 27377154 TI - A spliceosome intermediate with loosely associated tri-snRNP accumulates in the absence of Prp28 ATPase activity. AB - The precise role of the spliceosomal DEAD-box protein Prp28 in higher eukaryotes remains unclear. We show that stable tri-snRNP association during pre-catalytic spliceosomal B complex formation is blocked by a dominant-negative hPrp28 mutant lacking ATPase activity. Complexes formed in the presence of ATPase-deficient hPrp28 represent a novel assembly intermediate, the pre-B complex, that contains U1, U2 and loosely associated tri-snRNP and is stalled before disruption of the U1/5'ss base pairing interaction, consistent with a role for hPrp28 in the latter. Pre-B and B complexes differ structurally, indicating that stable tri snRNP integration is accompanied by substantial rearrangements in the spliceosome. Disruption of the U1/5'ss interaction alone is not sufficient to bypass the block by ATPase-deficient hPrp28, suggesting hPrp28 has an additional function at this stage of splicing. Our data provide new insights into the function of Prp28 in higher eukaryotes, and the requirements for stable tri-snRNP binding during B complex formation. PMID- 27377156 TI - Prostate cancer: Inhibiting initiation - targeting BMI1 is effective. PMID- 27377155 TI - Real-life effectiveness of omalizumab in severe allergic asthma above the recommended dosing range criteria. AB - BACKGROUND: Omalizumab (Xolair) dosing in severe allergic asthma is based on serum IgE and bodyweight. In Australia, patients eligible for omalizumab but exceeding recommended ranges for IgE (30-1500 IU/mL) and bodyweight (30-150 kg) may still receive a ceiling dose of 750 mg/4 weeks. About 62% of patients receiving government-subsidized omalizumab are enrolled in the Australian Xolair Registry (AXR). OBJECTIVES: To determine whether AXR participants above the recommended dosing ranges benefit from omalizumab and to compare their response to within-range participants. METHODS: Data were stratified according to dose range status (above-range or within-range). Further sub-analyses were conducted according to the reason for being above the dosing range (IgE only vs. IgE and weight). RESULTS: Data for 179 participants were analysed. About 55 (31%) were above recommended dosing criteria; other characteristics were similar to within range participants. Above-range participants had higher baseline IgE [812 (IQR 632, 1747) IU/mL vs. 209 (IQR 134, 306) IU/mL] and received higher doses of omalizumab [750 (IQR 650, 750) mg] compared to within-range participants [450 (IQR, 300, 600) mg]. At 6 months, improvements in Juniper 5-item Asthma Control Questionnaire (ACQ-5, 3.61 down to 2.01 for above-range, 3.47 down to 1.93 for within-range, P < 0.0001 for both) and Asthma Quality of Life Questionnaire (AQLQ mean score (3.22 up to 4.41 for above-range, 3.71 up to 4.88 for within-range, P < 0.0001) were observed in both groups. Forced expiratory volume in one second (FEV1 ) improved among above-range participants. There was no difference in response between above-range and within-range participants. Above-range participants due to either IgE alone or IgE and weight had similar improvements in ACQ-5, AQLQ and FEV1 . CONCLUSIONS AND CLINICAL RELEVANCE: Patients with severe allergic asthma above recommended dosing criteria for omalizumab have significantly improved symptom control, quality of life and lung function to a similar degree to within-range participants, achieved without dose escalation above 750 mg. PMID- 27377157 TI - Prostate cancer: Hypofractionated radiotherapy confirmed effective and safe. PMID- 27377158 TI - Kidney cancer: Cytoreductive nephrectomy improves outcomes in the era of targeted therapy. PMID- 27377159 TI - Prostate cancer: Novel subtyping could aid stratification and therapy. PMID- 27377160 TI - Bladder cancer: ASCO endorses EAU muscle-invasive bladder cancer guidelines. PMID- 27377162 TI - Branched and crosslinked supracolloidal chains with diblock copolymer micelles having three well-defined patches. AB - We report controlled branching and eventual crosslinking in supracolloidal chains by introducing well-defined trifunctional patchy micelles. Uniform micelles having three patches were induced from core-crosslinked micelles of diblock copolymers. Three patches in the micelles served as functional groups for crosslinking as well as branching in supracolloidal polymerization. PMID- 27377161 TI - The endocannabinoid system - a target for the treatment of LUTS? AB - Lower urinary tract symptoms (LUTS) are common in all age groups and both sexes, resulting in tremendous personal suffering and a substantial burden to society. Antimuscarinic drugs are the mainstay of symptom management in patients with LUTS, although their clinical utility is limited by the high prevalence of adverse effects, which often limit patients' long-term adherence to these agents. Data from controversial studies in the 1990s revealed the positive effects of marijuana-based compounds on LUTS, and sparked an interest in the possibility of treating bladder disorders with cannabis. Increased understanding of cannabinoid receptor pharmacology and the discovery of endogenous ligands of these receptors has prompted debate and further research into the clinical utility of exogenous cannabinoid receptor agonists relative to the unwanted psychotropic effects of these agents. Currently, the endocannabinoid system is considered as a potential drug target for pharmacological management of LUTS, with a more favourable adverse event profile than antimuscarinic agents. PMID- 27377163 TI - Successful Treatment of Pediatric Alopecia Areata of the Scalp Using Topical Bimatoprost. AB - Alopecia areata (AA) is a genetic and immune-mediated disease that targets anagen hair follicles. Despite limited evidence supporting the efficacy of corticosteroid treatments, they are often prescribed as first-line therapy because of their favorable safety profile. Prostaglandin analogues are currently being studied as an alternate therapy for scalp AA in adults. Herein we present a case of steroid-resistant multifocal AA that was successfully treated with topical bimatoprost. PMID- 27377165 TI - Purification of Logic-Qubit Entanglement. AB - Recently, the logic-qubit entanglement shows its potential application in future quantum communication and quantum network. However, the entanglement will suffer from the noise and decoherence. In this paper, we will investigate the first entanglement purification protocol for logic-qubit entanglement. We show that both the bit-flip error and phase-flip error in logic-qubit entanglement can be well purified. Moreover, the bit-flip error in physical-qubit entanglement can be completely corrected. The phase-flip in physical-qubit entanglement error equals to the bit-flip error in logic-qubit entanglement, which can also be purified. This entanglement purification protocol may provide some potential applications in future quantum communication and quantum network. PMID- 27377164 TI - Transition of differential histone H3 methylation in photoreceptors and other retinal cells during retinal differentiation. AB - To analyze cell lineage-specific transitions in global transcriptional and epigenetic changes during retinogenesis, we purified retinal cells from normal mice during postnatal development into two fractions, namely, photoreceptors and other retinal cells, based on Cd73 expression, and performed RNA sequencing and ChIP sequencing of H3K27me3 and H3K4me3. Genes expressed in the photoreceptor lineage were marked with H3K4me3 in the Cd73-positive cell fraction; however, the level of H3K27me3 was very low in both Cd73-positive and -negative populations. H3K27me3 may be involved in spatio-temporal onset of a subset of bipolar-related genes. Subsets of genes expressed in amacrine and retinal ganglion cells, which are early-born retinal cell types, were suggested to be maintained in a silent state by H3K27me3 during late-stage retinogenesis. In the outer nuclear layer, upregulation of Rho and rod-related genes were observed in Ezh2-ablated retina, suggesting a role for H3K27me3 in the maintenance of proper expression levels. Taken together, our data on the transition of lineage-specific molecular signatures during development suggest that histone methylation is involved in retinal differentiation and maintenance through cell lineage-specific mechanisms. PMID- 27377166 TI - Heveochlorella (Trebouxiophyceae): a little-known genus of unicellular green algae outside the Trebouxiales emerges unexpectedly as a major clade of lichen photobionts in foliicolous communities. AB - Foliicolous lichens are formed by diverse, highly specialized fungi that establish themselves and complete their life cycle within the brief duration of their leaf substratum. Over half of these lichen-forming fungi are members of either the Gomphillaceae or Pilocarpaceae, and associate with Trebouxia-like green algae whose identities have never been positively determined. We investigated the phylogenetic affinities of these photobionts to better understand their role in lichen establishment on an ephemeral surface. Thallus samples of Gomphillaceae and Pilocarpaceae were collected from foliicolous communities in southwest Florida and processed for sequencing of photobiont marker genes, algal cultivation and/or TEM. Additional specimens from these families and also from Aspidothelium (Thelenellaceae) were collected from a variety of substrates globally. Sequences from rbcL and nuSSU regions were obtained and subjected to Maximum Likelihood and Bayesian analyses. Analysis of 37 rbcL and 7 nuSSU algal sequences placed all photobionts studied within the provisional trebouxiophycean assemblage known as the Watanabea clade. All but three of the sequences showed affinities within Heveochlorella, a genus recently described from tree trunks in East Asia. The photobiont chloroplast showed multiple thylakoid stacks penetrating the pyrenoid centripetally as tubules lined with pyrenoglobuli, similar to the two described species of Heveochlorella. We conclude that Heveochlorella includes algae of potentially major importance as lichen photobionts, particularly within (but not limited to) foliicolous communities in tropical and subtropical regions worldwide. The ease with which they may be cultivated on minimal media suggests their potential to thrive free living as well as in lichen symbiosis. PMID- 27377167 TI - Improvement of the Water Resistance of a Narrow-Band Red-Emitting SrLiAl3 N4 :Eu(2+) Phosphor Synthesized under High Isostatic Pressure through Coating with an Organosilica Layer. AB - A SrLiAl3 N4 :Eu(2+) (SLA) red phosphor prepared through a high-pressure solid state reaction was coated with an organosilica layer with a thickness of 400-600 nm to improve its water resistance. The observed 4f(6) 5d->4f(7) transition bands are thought to result from the existence of Eu(2+) at two different Sr(2+) sites. Luminescence spectra at 10 K revealed two zero-phonon lines at 15377 (for Eu(Sr1)) and 15780 cm(-1) (for Eu(Sr2)). The phosphor exhibited stable red emission under high pressure up to 312 kbar. The configurational coordinate diagram gave a theoretical explanation for the Eu(2+/3+) result. The coated samples showed excellent moisture resistance while retaining an external quantum efficiency (EQE) of 70 % of their initial EQE after aging for 5 days under harsh conditions. White-light-emitting diodes of the SLA red phosphor and a commercial Y3 Al5 O12 :Ce(3+) yellow phosphor on a blue InGaN chip showed high color rendition (CRI=89, R9=69) and a low correlated color temperature of 2406 K. PMID- 27377168 TI - Risk factors predicting outcomes for primary refractory hodgkin lymphoma patients treated with salvage chemotherapy and autologous stem cell transplantation. AB - We aimed to identify risk factors that predict functional imaging (FI) response to salvage chemotherapy and evaluate outcomes following autologous stem cell transplant (ASCT) in primary refractory Hodgkin Lymphoma (HL). From 1 October 1994 to 10 July 2015, 192 primary refractory HL patients were treated on sequential second line protocols. Event-free survival (EFS) and overall survival (OS) were calculated from the date of histological confirmation of refractory disease. Covariates were analysed for relationship with FI response and EFS. By intent-to-treat, the median EFS was 8.9 years and OS 10.4 years with 41% having positive post-salvage FI. On multivariate analysis, the presence of B symptoms and bulk >=5 cm predicted for positive FI, with odds ratios of 2.15 and 2.03, respectively. For the 167 (87%) transplanted patients, 60% had a negative pre ASCT FI. Median EFS and OS were not reached with at a median follow-up of 3.6 years in surviving patients. Both stage IV refractory disease and persistent FI abnormality pre- ASCT were associated with worse outcomes: 3-year EFS was 84%, 54% and 28% for zero, 1 and 2 risk factors, respectively (P < 0.001). Further studies are needed to validate our prognostic model and to determine optimal therapy for patients with multiple risk factors. PMID- 27377169 TI - Low-grade myofibroblastic sarcoma: A population-based study. AB - OBJECTIVES/HYPOTHESIS: Low-grade myofibroblastic sarcoma (LGMS) is a rare entity that is described as having a predilection for occurring in the head and neck region. Here we analyze its demographics, clinic-pathologic, and survival characteristics. STUDY DESIGN: Retrospective database analysis. METHODS: A cohort from the Surveillance, Epidemiology, and End Results Program database of cases with LGMS between 2001 and 2012. RESULTS: There were 49 cases with a 5-year overall survival of 71.6% and disease- specific survival of 76.3%. The majority of cases were in patients <60 years old, female, and white ethnicity. The most common sites were the extremities in 40.8% of cases followed by the head and neck region with 26.5% of cases. Multivariate analysis showed that only older age was significantly associated with worse survival (P < .05). CONCLUSIONS: LGMS is uncommon in the United States and occurs most commonly in the extremities followed by the head and neck region, despite an existing characterization of a predilection for the head and neck region. Treatment most commonly involves surgery, but the optimal surgical extent and/or radiotherapy needs to be further investigated. LEVEL OF EVIDENCE: 2c Laryngoscope, 127:116-121, 2017. PMID- 27377170 TI - Compression of Morbidity Is Observed Across Cohorts with Exceptional Longevity. AB - OBJECTIVES: To determine, in a sample of Ashkenazi Jewish aged 95 and older, whether there is a compression of morbidity similar to what has been reported in other cohorts with exceptional longevity. DESIGN: Case-control study. SETTING: Longevity Genes Project (LGP) and New England Centenarian Study (NECS). PARTICIPANTS: LGP (n = 439, mean age 97.8 +/- 2.8) and NECS (n = 1,498, mean age 101.4 +/- 4.0) participants with exceptional longevity and their respective younger referent cohorts (LGP, n = 696; NECS, n = 302). MEASUREMENTS: Self- and proxy reports of age of onset of cancer, cardiovascular disease, diabetes mellitus, hypertension, osteoporosis, and stroke. RESULTS: Long-lived individuals from LGP and NECS had later age of onset of cancer, cardiovascular disease, diabetes mellitus, hypertension, and osteoporosis than their respective younger reference groups. The risk of overall morbidity was lower in participants with exceptional longevity than in younger participants (NECS men: relative risk (RR) = 0.12, women: RR = 0.20; LGP men: RR = 0.18, women: RR = 0.24). The age at which 20% of each of the groups with exceptional longevity experienced specific diseases was between 18 and 24 years later than in the reference groups, stratified according to sex. CONCLUSION: The similar extension of health span and compression of morbidity seen in NECS and LGP participants with exceptional longevity further validates the utility of these rare individuals for the study of factors that delay or prevent a broad spectrum of diseases otherwise associated with mortality and disability. PMID- 27377171 TI - Wheeled-mobility correlates of life-space and social participation in adult manual wheelchair users aged 50 and older. AB - PURPOSE: To characterize the life-space mobility and social participation of manual wheelchair users using objective measures of wheeled mobility. METHOD: Individuals (n = 49) were included in this cross-sectional study if they were aged 50 or older, community-dwelling and used their wheelchair on a daily basis for the past 6 months. Life-space mobility and social participation were measured using the life-space assessment and late-life disability instrument. The wheeled mobility variables (distance travelled, occupancy time, number of bouts) were captured using a custom-built data logger. RESULTS: After controlling for age and sex, multivariate regression analyses revealed that the wheeled mobility variables accounted for 24% of the life-space variance. The number of bouts variable, however, did not account for any appreciable variance above and beyond the occupancy time and distance travelled. Occupancy time and number of bouts were significant predictors of social participation and accounted for 23% of the variance after controlling for age and sex. CONCLUSIONS: Occupancy time and distance travelled are statistically significant predictors of life-space mobility. Lower occupancy time may be an indicative of travel to more distant life-spaces, whereas the distance travelled is likely a better reflection of mobility within each life-space. Occupancy time and number of bouts are significant predictors of participation frequency. Implications for rehabilitation Component measures of wheelchair mobility, such as distance travelled, occupancy time and number of bouts, are important predictors of life space mobility and social participation in adult manual wheelchair users. Lower occupancy time is an indication of travel to more distant life-spaces, whereas distance travelled is likely a better reflection of mobility within each life space. That lower occupancy time and greater number of bouts are associated with more frequent participation raises accessibility and safety issues for manual wheelchair users. PMID- 27377172 TI - Role of perfusion CT in the evaluation of functional primary tumour response after radiochemotherapy in head and neck cancer: preliminary findings. AB - OBJECTIVE: To report the initial results of a prospective study aimed at evaluating the CT perfusion parameter changes (?PCTp) of the primary tumour after radiochemotherapy (RCT) in head and neck cancer (HNC) and to correlate with positron emission tomography (PET)/CT response. METHODS: Eligibility criteria included HNC (Stage III-IV) candidates for RCT. Patients underwent perfusion CT (PCT) at baseline and at 3 weeks and 3 months after treatment. Blood volume, blood flow, mean transit time (MTT) and permeability surface (PS) product were computed. Moreover, PET/CT was performed at baseline and 3 months after treatment. The ?PCTp were evaluated between baseline and 3-week/3-month evaluations, whereas PET/CT response was based on the maximum standardized uptake value changes according to the European Organization for Research and Treatment of Cancer criteria. RESULTS: Between July 2012 and July 2015, 25 patients were enrolled. A significant reduction of all CT tumour perfusion parameters (PCTp) was observed from the baseline to after RCT (p < 0.001). Specifically, a significant reduction was shown at 3 weeks for all PCTp except MTT (from 6.18 to 5.14 s; p = 0.722). Differently, a significant reduction of all PCTp (p < 0.001) including MTT (from 6.18 to 2.24 s; p = 0.001) was shown at 3 months. Moreover, the reduction of PS resulted in a significant prediction of PET/CT response at 3 months (p = 0.037) with the trend also at 3 weeks (p = 0.099) at the multivariate analysis. CONCLUSION: Our preliminary findings seem to show that almost all PCTp are significantly reduced after RCT, whereas PS seems to come out as the strongest factor in predicting the PET/CT response. ADVANCES IN KNOWLEDGE: This article provides information on the potential useful role of PCT in evaluating tumour response after both early and late RCT. PMID- 27377174 TI - Flow-Through Electroporation of HL-60 White Blood Cell Suspensions using Nanoporous Membrane Electrodes. AB - A flow-through electroporation system, based on a novel nanoporous membrane/electrode design, for the delivery of cell wall-impermeant molecules into model leukocytes, HL-60 promyelocytes, was demonstrated. The ability to apply low voltages to cell populations, with nm-scale concentrated electric field in a periodic array, contributes to high cell viability. With applied biases of 1 4V, delivery of target molecules was achieved with 90% viability and up to 65% transfection efficiency. More importantly, the system allowed electrophoretic pumping of molecules from a microscale reservoir across the membrane/electrode system into a microfluidic flow channel for transfection of cells, a design that can reduce reagent amount by eightfold compared to current strategies. The flow through system, which forces intimate membrane/electrode contact by using a 10MUm channel height, can be easily scaled-up by adjusting the microfluidic channel geometry and/or the applied voltage pulse frequency to control cell residence times at the cell membrane/electrode interface. The demonstrated system shows promise in clinical applications where low-cost, high cell viability and high volume transfection methods are needed without the risk of viral vectors. In particular genetic modification of freely mobile white blood cells to either target disease cells or to express desired protein/enzyme biomolecules is an important target platform enabled by this device system. PMID- 27377173 TI - CO2-evoked release of PGE2 modulates sighs and inspiration as demonstrated in brainstem organotypic culture. AB - Inflammation-induced release of prostaglandin E2 (PGE2) changes breathing patterns and the response to CO2 levels. This may have fatal consequences in newborn babies and result in sudden infant death. To elucidate the underlying mechanisms, we present a novel breathing brainstem organotypic culture that generates rhythmic neural network and motor activity for 3 weeks. We show that increased CO2 elicits a gap junction-dependent release of PGE2. This alters neural network activity in the preBotzinger rhythm-generating complex and in the chemosensitive brainstem respiratory regions, thereby increasing sigh frequency and the depth of inspiration. We used mice lacking eicosanoid prostanoid 3 receptors (EP3R), breathing brainstem organotypic slices and optogenetic inhibition of EP3R(+/+) cells to demonstrate that the EP3R is important for the ventilatory response to hypercapnia. Our study identifies a novel pathway linking the inflammatory and respiratory systems, with implications for inspiration and sighs throughout life, and the ability to autoresuscitate when breathing fails. PMID- 27377175 TI - Semi-Automatic Rating Method for Neutrophil Alkaline Phosphatase Activity. AB - BACKGROUND: The neutrophil alkaline phosphatase (NAP) score is a valuable test for the diagnosis of myeloproliferative neoplasms, but it has still manually rated. Therefore, we developed a semi-automatic rating method using Photoshop(r) and Image-J, called NAP-PS-IJ. METHODS: Neutrophil alkaline phosphatase staining was conducted with Tomonaga's method to films of peripheral blood taken from three healthy volunteers. At least 30 neutrophils with NAP scores from 0 to 5+ were observed and taken their images. From which the outer part of neutrophil was removed away with Image-J. These were binarized with two different procedures (P1 and P2) using Photoshop(r) . NAP-positive area (NAP-PA) and granule (NAP-PGC) were measured and counted with Image-J. RESULTS: The NAP-PA in images binarized with P1 significantly (P < 0.05) differed between images with NAP scores from 0 to 3+ (group 1) and those from 4+ to 5+ (group 2). The original images in group 1 were binarized with P2. NAP-PGC of them significantly (P < 0.05) differed among all four NAP score groups. The mean NAP-PGC with NAP-PS-IJ indicated a good correlation (r = 0.92, P < 0.001) to results by human examiners. CONCLUSIONS: The sensitivity and specificity of NAP-PS-IJ were 60% and 92%, which might be considered as a prototypic method for the full-automatic rating NAP score. PMID- 27377176 TI - Simple field-based automated dispersive liquid-liquid microextraction of trace level phthalate esters in natural waters with gas chromatography and mass spectrometric analysis. AB - A small, simple, and field-based automated dispersive liquid-liquid microextraction method followed by gas chromatography mass spectrometric analysis was developed for trace level phthalate esters analysis in natural waters. With a single syringe pump that is coupled with a multiposition valve, the whole extraction procedure including cleaning, sampling, mixing of extractant and disperser solvents, extraction, phase separation, and analytes collection was carried out in a totally automated way with a sample throughput of 21 h(-1) . Key factors, such as type and ratio of the extractant and disperser solvent, aspiration flow rate, extraction time, and matrix effect, were thoroughly investigated. Under the optimum conditions, linearity was found in the range from 0.03 to 60 MUg/L. Limits of detection ranged from 0.0015 to 0.003 MUg/L. Enrichment factors were in a range of 106-141. Reproducibility and recoveries were assessed by testing a series of three natural water samples that were spiked with different concentration levels. Finally, the proposed method was successfully applied in analysis of real surface waters. The developed system is inexpensive, light (2.6 kg), simple to use, applicable in the field, with high sample throughput, and sensitive enough for trace level phthalate esters analysis in natural waters. PMID- 27377177 TI - Ligand-controlled stereodivergent 1,3-dipolar cycloaddition of azomethine ylides with 3-methyl-4-nitro-5-styrylisoxazoles. AB - An unprecedented Ag(i)-catalyzed ligand-controlled stereodivergent 1,3-dipolar cycloaddition of azomethine ylides with 3-methyl-4-nitro-5-styrylisoxazoles has been developed to afford heterocycles bearing both methylisoxazole and pyrrolidine moieties. The endo- and exo-cycloadducts were obtained in good yields with excellent stereoselectivities, assisted by (t)Bu-Phosferrox and phosphoramidite as chiral ligands, respectively. PMID- 27377178 TI - Acute Lower Limb Ischaemia and Diabetes in a Patient Treated with Anti-PD1 Monoclonal Antibody for Metastatic Melanoma. PMID- 27377180 TI - The intricacy of biomarker complexity-the identification of a genuine proteomic biomarker is more complicated than believed. AB - Several reasons have been put forward to explain the irreproducibility of proteomic biomarker search. However, these reasons pertain to almost every part of biomarker search across the entire analytical workflow but are entirely experimental or methodological. However, in this article we point out that there is a further cause of such irreproducibility. This is not an additional methodological or experimental cause but arises directly from the biology of protein expression. It arises from the fact that disease changes the diversity within protein families. This cause of irreproducibility has been very little studied in relation to proteomic biomarker search. Gene expression is highly variable even in healthy people. Therefore, multiple proteoforms are also to be expected when gene expression is disrupted by disease, proteoforms that may be differently altered by pathology. In consequence, it is illogical to expect that the whole protein family produces a reliably usable biomarker. It is more reasonable to expect that a specific proteoform fulfills this role. Appropriate sample pre-fractionation methods and data analyses could help to identify this version, carrying the modification or the epitope required. PMID- 27377181 TI - Preserved entropy and fragile magnetism. AB - A large swath of quantum critical and strongly correlated electron systems can be associated with the phenomena of preserved entropy and fragile magnetism. In this overview we present our thoughts and plans for the discovery and development of lanthanide and transition metal based, strongly correlated systems that are revealed by suppressed, fragile magnetism, quantum criticality, or grow out of preserved entropy. We will present and discuss current examples such as YbBiPt, YbAgGe, YbFe2Zn20, PrAg2In, BaFe2As2, CaFe2As2, LaCrSb3 and LaCrGe3 as part of our motivation and to provide illustrative examples. PMID- 27377182 TI - Changes in antithrombotic therapy after a cerebrovascular or coronary ischemic event in the WARfarin and coronary STENTing (WAR-STENT) registry. PMID- 27377183 TI - Size dependent electrochemical detection of trace heavy metal ions based on nano patterned carbon sphere electrodes. AB - The challenge in efficient electrochemical detection of trace heavy metal ions (HMI) for early warning is to construct an electrode with a nano-patterned architecture. In this study, a range of carbon electrodes with ordered structures were fabricated using colloidal hollow carbon nanospheres (HCSs) as sensing materials for trace HMI (represented by Pb(ii)) detection by square wave anodic stripping voltammetry. The regular geometrical characteristics of the carbon electrode allow it to act as a model system for the estimation of electron transfer pathways by calculating contact points between HCSs and a glassy carbon electrode. A clear correlation between the contact points and the electron transfer resistance has been established, which fits well with the quadratic function model and is dependent on the size of HCSs. To our knowledge, this is the first clear function that expresses the structure-sensing activity relationship of carbon-based electrodes. The prepared carbon electrode is capable of sensing Pb(ii) with a sensitivity of 0.160 MUA nM(-1), which is much higher than those of other electrodes reported in the literature. Its detection limit of 0.6 nM is far below the guideline value (72 nM) given by the US Environmental Protection Agency. In addition, the carbon electrode could be a robust alternative to various heavy metal sensors. PMID- 27377184 TI - Dearomatization through Halofunctionalization Reactions. AB - Recent advances in dearomatization through halofunctionalization reactions are summarized in this Minireview. Two general categories of strategies are currently employed in this field. On one hand, the reaction can be initiated with electrophilic halogenation at an alkyne or alkene moiety. The resulting halonium ion intermediate is then captured by a pendant aromatic ring at the ipso position, affording the dearomatization product. On the other hand, electrophilic halogenation can directly take place at a substituted arene, and the final dearomatization product is furnished by deprotonation or intramolecular nucleophilic trap. Highly enantioselective variants have been realized in the latter case by organocatalysis or transition metal catalysis. By applying these methods, various valuable halogenated polycyclic molecular architectures have been obtained from readily available starting materials. PMID- 27377185 TI - High Dielectric and Mechanical Properties Achieved in Cross-Linked PVDF/alpha-SiC Nanocomposites with Elevated Compatibility and Induced Polarization at the Interface. AB - Remarkably improved dielectric properties including high-k, low loss, and high breakdown strength combined with promising mechanical performance such as high flexibility, good heat, and chemical resistivity are hard to be achieved in high k dielectric composites based on the current composite fabrication strategy. In this work, a family of high-k polymer nanocomposites has been fabricated from a facile suspension cast process followed by chemical cross-linking at elevated temperature. Internal double bonds bearing poly(vinylidene fluoride chlorotrifluoroethylene) (P(VDF-CTFE-DB)) in total amorphous phase are employed as cross-linkable polymer matrix. alpha-SiC particles with a diameter of 500 nm are surface modified with 3-aminpropyltriethoxysilane (KH-550) as fillers for their comparable dielectric performance with PVDF polymer matrix, low conductivity, and high breakdown strength. The interface between SiC particles and PVDF matrix has been finely tailored, which leads to the significantly elevated dielectric constant from 10 to over 120 in SiC particles due to the strong induced polarization. As a result, a remarkably improved dielectric constant (ca. 70) has been observed in c-PVDF/m-SiC composites bearing 36 vol % SiC, which could be perfectly predicted by the effective medium approximation (EMA) model. The optimized interface and enhanced compatibility between two components are also responsible for the depressed conductivity and dielectric loss in the resultant composites. Chemical cross-linking constructed in the composites results in promising mechanical flexibility, good heat and chemical stability, and elevated tensile performance of the composites. Therefore, excellent dielectric and mechanical properties are finely balanced in the PVDF/alpha-SiC composites. This work might provide a facile and effective strategy to fabricate high-k dielectric composites with promising comprehensive performance. PMID- 27377186 TI - Identification, Characterization, and X-ray Crystallographic Analysis of a Novel Type of Mannose-Specific Lectin CGL1 from the Pacific Oyster Crassostrea gigas. AB - A novel mannose-specific lectin, named CGL1 (15.5 kDa), was isolated from the oyster Crassostrea gigas. Characterization of CGL1 involved isothermal titration calorimetry (ITC), glycoconjugate microarray, and frontal affinity chromatography (FAC). This analysis revealed that CGL1 has strict specificity for the mannose monomer and for high mannose-type N-glycans (HMTGs). Primary structure of CGL1 did not show any homology with known lectins but did show homology with proteins of the natterin family. Crystal structure of the CGL1 revealed a unique homodimer in which each protomer was composed of 2 domains related by a pseudo two-fold axis. Complex structures of CGL1 with mannose molecules showed that residues have 8 hydrogen bond interactions with O1, O2, O3, O4, and O5 hydroxyl groups of mannose. The complex interactions that are not observed with other mannose binding lectins revealed the structural basis for the strict specificity for mannose. These characteristics of CGL1 may be helpful as a research tool and for clinical applications. PMID- 27377187 TI - Proteolysis of plasminogen activator inhibitor-1 by Yersinia pestis remodulates the host environment to promote virulence. AB - Essentials Effect of plasminogen activator inhibitor (PAI)-1 on plague and its Y. pestis cleavage is unknown. An intranasal mouse model of infection was used to determine the role of PAI-1 in pneumonic plague. PAI-1 is cleaved and inactivated by the Pla protease of Y. pestis in the lung airspace. PAI-1 impacts both bacterial outgrowth and the immune response to respiratory Y. pestis infection. Click to hear Dr Bock discuss pathogen activators of plasminogen. SUMMARY: Background The hemostatic regulator plasminogen activator inhibitor-1 (PAI-1) inactivates endogenous plasminogen activators and aids in the immune response to bacterial infection. Yersinia pestis, the causative agent of plague, produces the Pla protease, a virulence factor that is required during plague. However, the specific hemostatic proteins cleaved by Pla in vivo that contribute to pathogenesis have not yet been fully elucidated. Objectives To determine whether PAI-1 is cleaved by the Pla protease during pneumonic plague, and to define the impact of PAI-1 on Y. pestis respiratory infection in the presence or absence of Pla. Methods An intranasal mouse model of pneumonic plague was used to assess the levels of total and active PAI-1 in the lung airspace, and the impact of PAI-1 deficiency on bacterial pathogenesis, the host immune response and plasmin generation following infection with wild-type or ?pla Y. pestis. Results We found that Y. pestis cleaves and inactivates PAI-1 in the lungs in a Pla-dependent manner. The loss of PAI-1 enhances Y. pestis outgrowth in the absence of Pla, and is associated with increased conversion of plasminogen to plasmin. Furthermore, we found that PAI-1 regulates immune cell recruitment, cytokine production and tissue permeability during pneumonic plague. Conclusions Our data demonstrate that PAI-1 is an in vivo target of the Pla protease in the lungs, and that PAI-1 is a key regulator of the pulmonary innate immune response. We conclude that the inactivation of PAI-1 by Y. pestis alters the host environment to promote virulence during pneumonic plague. PMID- 27377188 TI - Structure-Function Correlation of Aminated Poly(alpha)glutamate as siRNA Nanocarriers. AB - It has been two decades since cationic polymers were introduced to the world of oligonucleotides delivery. However, the optimal physicochemical properties to make them a successful delivery vehicle are yet unknown. An ideal system became particularly interesting and necessary with the introduction of RNA interference as a promising therapeutic approach. Such nanocarrier should overcome challenges such as low plasma stability, poor cellular internalization and endosomal escape to induce gene silencing. To that end, we synthesized a library of biodegradable aminated poly(alpha)glutamate varied by amine moieties. In an attempt to elucidate the structure-function relationship, our polyplexes were physicochemically characterized and their silencing activity and cytotoxicity were evaluated. We found several structures that demonstrated improved cellular internalization. These candidates silenced gene expression to less than 50% of their initial levels, while being safe to cells and mice. Based on our research, an improved and promising tailor-designed siRNA delivery platform can be developed. PMID- 27377189 TI - Dispersive liquid-liquid microextraction of quinolones in porcine blood: Optimization of extraction procedure and CE separation using experimental design. AB - A dispersive liquid-liquid microextraction procedure was developed to extract nine fluoroquinolones in porcine blood, six of which were quantified using a univariate calibration method. Extraction parameters including type and volume of extraction and dispersive solvent and pH, were optimized using a full factorial and a central composite designs. The optimum extraction parameters were a mixture of 250 MUL dichloromethane (extract solvent) and 1250 MUL ACN (dispersive solvent) in 500 MUL of porcine blood reached to pH 6.80. After shaking and centrifugation, the upper phase was transferred in a glass tube and evaporated under N2 steam. The residue was resuspended into 50 MUL of water-ACN (70:30, v/v) and determined by CE method with DAD, under optimum separation conditions. Consequently, a tenfold enrichment factor can potentially be reached with the pretreatment, taking into account the relationship between initial sample volume and final extract volume. Optimum separation conditions were as follows: BGE solution containing equal amounts of sodium borate (Na2 B4 O7 ) and di-sodium hydrogen phosphate (Na2 HPO4 ) with a final concentration of 23 mmol/L containing 0.2% of poly (diallyldimethylammonium chloride) and adjusted to pH 7.80. Separation was performed applying a negative potential of 25 kV, the cartridge was maintained at 25.0 degrees C and the electropherograms were recorded at 275 nm during 4 min. The hydrodynamic injection was performed in the cathode by applying a pressure of 50 mbar for 10 s. PMID- 27377190 TI - Influence of arginine on the growth, arginine metabolism and amino acid consumption profiles of Streptococcus thermophilus T1C2 in controlled pH batch fermentations. AB - AIMS: The aim of this study was to elucidate the effect of arginine on the growth, arginine metabolism and amino acid consumption profiles of Streptococcus thermophilus T1C2. METHODS AND RESULTS: The growth kinetics, intracellular pH, extracellular osmotic pressure, expression of key genes in the arginine metabolism pathway and amino acid consumption profiles were analysed in chemically defined medium with different initial arginine concentrations. The results showed that arginine stimulated the growth of Strep. thermophilus T1C2 under low intracellular pH and high extracellular osmotic pressure. The expression of key genes in the arginine degradation pathway indicated that arginine relieved the drop in the intracellular pH by consuming protons and generating NH3 . Additionally, the results showed that arginine degradation did not occur via the arginine deiminase pathway but through the arginine decarboxylase-urease pathway. Furthermore, the utilization efficiency of amino acids was improved in the presence of arginine. CONCLUSIONS: Arginine improved the growth of Strep. thermophilus due to protecting Strep. thermophilus against intracellular acid stress, which was revealed at the transcriptional level of key genes. This study showed that the acid resistance of Strep. thermophilus was achieved through the arginine decarboxylase-urease pathway. SIGNIFICANCE AND IMPACT OF THE STUDY: The arginine-stimulated growth of Strep. thermophilus improved the utilization efficiency of amino acids and reduced nitrogen waste, which could be useful for the optimization of cultivation media. PMID- 27377191 TI - Immobilized Artificial Membrane HPLC Derived Parameters vs PAMPA-BBB Data in Estimating in Situ Measured Blood-Brain Barrier Permeation of Drugs. AB - The affinity indexes for phospholipids (log kW(IAM)) for 42 compounds were measured by high performance liquid chromatography (HPLC) on two different phospholipid-based stationary phases (immobilized artificial membrane, IAM), i.e., IAM.PC.MG and IAM.PC.DD2. The polar/electrostatic interaction forces between analytes and membrane phospholipids (Deltalog kW(IAM)) were calculated as the differences between the experimental values of log kW(IAM) and those expected for isolipophilic neutral compounds having polar surface area (PSA) = 0. The values of passage through a porcine brain lipid extract (PBLE) artificial membrane for 36 out of the 42 compounds considered, measured by the so-called PAMPA-BBB technique, were taken from the literature (P0(PAMPA-BBB)). The values of blood-brain barrier (BBB) passage measured in situ, P0(in situ), for 38 out of the 42 compounds considered, taken from the literature, represented the permeability of the neutral forms on "efflux minimized" rodent models. The present work was aimed at verifying the soundness of Deltalog kW(IAM) at describing the potential of passage through the BBB as compared to data achieved by the PAMPA-BBB technique. In a first instance, the values of log P0(PAMPA-BBB) (32 data points) were found significantly related to the n-octanol lipophilicity values of the neutral forms (log P(N)) (r(2) = 0.782) whereas no significant relationship (r(2) = 0.246) was found with lipophilicity values of the mixtures of ionized and neutral forms existing at the experimental pH 7.4 (log D(7.4)) as well as with either log kW(IAM) or Deltalog kW(IAM) values. log P0(PAMPA-BBB) related moderately to log P0(in situ) values (r(2) = 0.604). The latter did not relate with either n-octanol lipophilicity indexes (log P(N) and log D(7.4)) or phospholipid affinity indexes (log kW(IAM)). In contrast, significant inverse linear relationships were observed between log P0(in situ) (38 data points) and Deltalog kW(IAM) values for all the compounds but ibuprofen and chlorpromazine, which behaved as moderate outliers (r(2) = 0.656 and r(2) = 0.757 for values achieved on IAM.PC.MG and IAM.PC.DD2, respectively). Since log P0(in situ) refer to the "intrinsic permeability" of the analytes regardless their ionization degree, no correction for ionization of Deltalog kW(IAM) values was needed. Furthermore, log P0(in situ) were found roughly linearly related to log BB values (i.e., the logarithm of the ratio brain concentration/blood concentration measured in vivo) for all the analytes but those predominantly present at the experimental pH 7.4 as anions. These results suggest that, at least for the data set considered, Deltalog kW(IAM) parameters are more effective than log P0(PAMPA BBB) at predicting log P0(in situ) values for all the analytes. Furthermore, ionization appears to affect differently, and much more markedly, BBB passage of acids (yielding anions) than that of the other ionizable compounds. PMID- 27377193 TI - Spontaneous bilateral and concurrent cerebrospinal fluid otorrhoea: case presentation and literature review. AB - BACKGROUND: Cerebrospinal fluid otorrhoea is a rare entity. Only a few cases of spontaneous bilateral cerebrospinal fluid otorrhoea have been reported. In all cases, there was a definite time interval between the two (left and right) presentations. OBJECTIVES: To raise awareness and report on the very rare entity of bilateral spontaneous cerebrospinal fluid otorrhoea. CASE REPORT: This paper reports the case of a bilateral, synchronous, spontaneous cerebrospinal fluid otorrhoea in a 44-year-old female. The patient had grommets surgically inserted on two separate occasions for treatment of otitis media with effusion, and received several courses of oral and topical antibiotics. Five years following the patient's initial presentation, a suspicion of concurrent bilateral cerebrospinal fluid otorrhoea was raised. The otorrhoea sample collected proved to be cerebrospinal fluid. Cross-sectional imaging revealed bilateral defects in the tegmen tympani of the skull base. She underwent staged middle fossa craniotomies to repair the defects. CONCLUSION: Careful observation of the middle ear fluid characteristics following myringotomy can allow for prompt diagnosis. PMID- 27377192 TI - Safety, complications and patients' acceptance of Mohs micrographic surgery under local anaesthesia: results from the U.K. MAPS (Mohs Acceptance and Patient Safety) Collaboration Group. PMID- 27377194 TI - EX VIVO CORRELATION OF ULTRASONOGRAPHIC SMALL INTESTINAL WALL LAYERING WITH HISTOLOGY IN DOGS. AB - Canine ultrasonographic intestinal layers have been reported to correlate with histological layering. However, discrepancies have been reported in people, and additional layers visualized. The aim of this method comparison study was to describe ex vivo canine small intestinal layering and correlate it with histology. Small intestinal samples of 12 adult dogs euthanized for reasons unrelated to gastrointestinal disease were resected immediately following euthanasia, pinned on a Petri dish, and transverse ultrasonographic images acquired in a water bath, using a high-frequency linear transducer. Transverse histological sections were obtained at the same level. Measurements of the intestinal layers were performed on the ultrasonographic and histological images. No significant statistical differences were noted between the ultrasonographic and histological measurements and strong to very strong (r > 0.7) positive correlation was observed for all layers, except for the serosa, which had a low moderate positive correlation (r = 0.479). In addition to the five established layers, a dual mucosal echogenicity was consistently observed, with seven samples presenting an additional inner mucosal severe hyperechogenicity. Histologically, this dual echogenicity was attributed to the intestinal villi (mildly echogenic) and lamina propria (hypoechoic). The additional inner mucosal severe hyperechogenicity observed in seven samples was attributed to mild-to-moderate lacteal dilation histologically. In 4/12 ileal samples, an additional hyperechoic mucosal line was also observed parallel to the submucosa, corresponding histologically to prominent Peyer's patches. Finally, a hyperechoic line was observed within the muscularis of all samples, corresponding histologically to the interface between the muscularis longitudinal and circular layers. PMID- 27377195 TI - Supplementation of Diabetic Rats with Leucine, Zinc, and Chromium: Effects on Function and Histological Structure of Testes. AB - The objective was to study whether leucine, zinc, and chromium supplementations influence function and histological structure of testes in a rat model of type 2 diabetes. Seventy seven adult male rats were categorized into 11 groups of 7 animals each: (1) nondiabetic (negative control); (2) non-treated (positive control); (3) treated with insulin; (4) treated with glibenclamide; (5) treated with leucine; (6) treated with zinc; (7) treated with chromium; (8) treated with leucine + zinc; (9) treated with leucine + chromium; (10) treated with zinc + chromium; (11) treated with leucine + zinc + chromium. In the non-treated group, hyperglycemia severely damaged testes morphology as well as the spermatogenic process. Diabetes induction decreased testicular length, height, width, volume, total number of epididymal sperm, and number of live sperm. Seminiferous tubules of diabetic rats showed a decrease in diameter of tubules and height of epithelium. Diabetes induction decreased the number of cells (spermatogonia, spermatocyte, spermatid, and Sertoli) in cross sections of seminiferous tubules. Administration of nutritional supplements to the diabetic rats improved testes morphology and reversed, although not completely, impairment of spermatogenesis. Treatment with nutritional supplements increased testicular length, height, width, and volume. All treatments increased the number of live sperm and the total number of epididymal sperm. Furthermore, nutritional supplements increased diameter of tubules, height of epithelium, and the number of cells in seminiferous tubules. These alleviating effects were more pronounced in animals treated with the leucine-zinc-chromium combination. The present results demonstrate beneficial effects of zinc, leucine, and chromium supplements to improve testes morphology and to restore spermatogenesis in type 2 diabetic rats. PMID- 27377196 TI - Multiplexing slanted spiral microchannels for ultra-fast blood plasma separation. AB - Blood and blood products are critical components of health care. Blood components perform distinct functions in the human body and thus the ability to efficiently fractionate blood into its individual components (i.e., plasma and cellular components) is of utmost importance for therapeutic and diagnostic purposes. Although conventional approaches like centrifugation and membrane filtration for blood processing have been successful in generating relatively pure fractions, they are largely limited by factors such as the required blood sample volume, component purity, clogging, processing time and operation efficiency. In this work, we developed a high-throughput inertial microfluidic system for cell focusing and blood plasma separation from small to large volume blood samples (1 100 mL). Initially, polystyrene beads and blood cells were used to investigate the inertial focusing performance of a single slanted spiral microchannel as a function of particle size, flow rate, and blood cell concentration. Afterwards, blood plasma separation was conducted using an optimised spiral microchannel with relatively large dimensions. It was found that the reject ratio of the slanted spiral channel is close to 100% for blood samples with haematocrit (HCT) values of 0.5% and 1% under an optimal flow rate of 1.5 mL min(-1). Finally, through a unique multiplexing approach, we built a high-throughput system consisting of 16 spiral channels connected together, which can process diluted samples with a total flow rate as high as 24 mL min(-1). The proposed multiplexed system can surmount the shortcomings of previously reported microfluidic systems for plasma separation and cell sorting in terms of throughput, yield and operation efficiency. PMID- 27377197 TI - Single-pixel three-dimensional imaging with time-based depth resolution. AB - Time-of-flight three-dimensional imaging is an important tool for applications such as object recognition and remote sensing. Conventional time-of-flight three dimensional imaging systems frequently use a raster scanned laser to measure the range of each pixel in the scene sequentially. Here we show a modified time-of flight three-dimensional imaging system, which can use compressed sensing techniques to reduce acquisition times, whilst distributing the optical illumination over the full field of view. Our system is based on a single-pixel camera using short-pulsed structured illumination and a high-speed photodiode, and is capable of reconstructing 128 * 128-pixel resolution three-dimensional scenes to an accuracy of ~3 mm at a range of ~5 m. Furthermore, by using a compressive sampling strategy, we demonstrate continuous real-time three dimensional video with a frame-rate up to 12 Hz. The simplicity of the system hardware could enable low-cost three-dimensional imaging devices for precision ranging at wavelengths beyond the visible spectrum. PMID- 27377198 TI - Labeling Pathological Tau: An Important Quest for the Unknown. PMID- 27377199 TI - Clinical and neuroimaging differences between posterior cortical atrophy and typical amnestic Alzheimer's disease patients at an early disease stage. AB - To identify clinical and neuroimaging characteristics between posterior cortical atrophy (PCA) and typical amnestic Alzheimer's disease (tAD) patients at an early disease stage, 16 PCA and 13 age-matched tAD patients were enrolled. Compared with tAD patients, PCA patients showed higher mean recognition and recall test scores, and lower mean calculation, spatial attention, shape discrimination, and writing test scores. Mean right hippocampal volume was larger in PCA patients compared with tAD patients, while cortical gray matter (GM) volume of bilateral parietal and occipital lobes was smaller in PCA patients. Further, when compared with tAD patients, significant hypometabolism was observed in bilateral parietal and occipital lobes, particularly the right occipitotemporal junction in PCA patients. Additionally, there were significant positive correlations in recognition and recall scores with hippocampal volumes. In PCA patients, calculation and visuospatial ability scores are positively associated with GM volume of parietal and occipital lobes. And only spatial attention and shape discrimination scores are positively associated with regional glucose metabolism of parietal and occipital lobes. Therefore, PCA patients display better recognition and recall scores, which are associated with larger hippocampal volumes and poorer performance in visual spatial tasks because of marked GM atrophy and hypometabolism of parietal and occipital lobes. PMID- 27377201 TI - New address of ARSMB/KVBMG The ARSMB - KVBMG Royal Association of the Medical Scientific Societies of Belgium Moves to Avenue Winston Churchill 11, box 30 - B 1180 Brussels (Uccle). PMID- 27377200 TI - Multi agency working in forensic psychiatry: Theory and practice in Europe. PMID- 27377202 TI - Twelve Steps to Writing an Effective "Materials and Methods"-section. PMID- 27377203 TI - Percutaneous Viabahn-Assisted Subintimai Recanalization (VASIR) for Severe Femoropopliteal Occlusive Disease. PMID- 27377204 TI - Risk of Active Tuberculosis among Index Case of Householders-A Long-Term Assessment after the Conventional Contacts Study. AB - OBJECTIVES: The aim of this study was to determine the incidence of active tuberculosis (TB) among household contacts of TB-index cases diagnosed during a 7 year period in a public Primary Care Center located in a high-incidence area. DESIGN AND SAMPLE: A retrospective cohort study was performed. Data collection was based on the capture-recapture method; the two main sources crossed information from TB-index and contact cases from the El Fondo Primary Care Center (Santa Coloma de Gramenet, Spain) and their reports to the National Epidemiologic Surveillance Service. MEASURES: Variables were divided into demographic and health data (result of the Mantoux test, chest X-ray, presence of risk factors, and indication for chemoprophylaxis). RESULTS: Community nurses identified 103 household contacts that underwent the conventional contact study. Overall, 60.19% were male; the mean age was 29.08 years. Only one case of secondary active TB was found, representing an incidence of 0.56% per TB-index case and year. CONCLUSION: The incidence of new secondary TB among household contacts with TB-index cases was of a case. Nevertheless, a long-term follow-up of these householders beyond the conventional contacts study should be considered in areas with higher incidences of TB or among specific high-risk populations. PMID- 27377205 TI - Polysomnography findings in spinocerebellar ataxia type 6. AB - Spinocerebellar ataxia type 6 (SCA6) is usually described as a pure ataxia syndrome. However, SCA6 patients may have sleep complaints. In this paper, sleep disorders were investigated in patients with SCA6. Twelve SCA6 patients and 12 subjects matched by gender, age and body mass index (control group) underwent polysomnography and clinical investigation for sleep disorders. SCA6 had a higher frequency of snoring (P = 0.01), a higher index of awakening due to respiratory events (P = 0.003) and central apnea events during sleep (P = 0.024), a longer sleep Stage N1 (P = 0.02) and a lower sleep Stage N3 (P = 0.05) in SCA6 patients than in control subjects. SCA6 patients had a reduction in slow wave sleep and a higher frequency of snoring and respiratory disorders during sleep when compared to the control group. PMID- 27377206 TI - Reference values for maximum respiratory pressures in patients with type 2 diabetes mellitus. PMID- 27377207 TI - Do skeletal-related events predict overall survival in men with metastatic castration-resistant prostate cancer? AB - BACKGROUND: Skeletal-related events (SREs) including pathologic fracture, spinal cord compression, radiation to bone and surgery to bone, are common in men with bone metastatic castration-resistant prostate cancer (mCRPC). Men with mCRPC are at high risk of death. Whether SREs predict mortality is unclear. We tested the association between SREs and overall survival (OS) in a multiethnic cohort with bone mCRPC, controlling for key covariates unavailable in claims data such as bone pain, number of bone metastases and PSA doubling time (PSADT). METHODS: We collected data on 233 men diagnosed with nonmetastatic castration-resistant prostate cancer (CRPC) in 2000-2013 at two Veterans Affairs hospitals who later progressed to bone metastases. First occurrence of SRE and OS were collected from the medical records. Cox models were used to test the association between SRE and OS, treating SRE as a time-dependent variable. We adjusted for age, year, race, treatment center, biopsy Gleason, primary treatment to the prostate, PSA, PSADT, months from androgen deprivation therapy to CRPC, months from CRPC to metastasis and number of bone metastases at initial bone metastasis diagnosis. In a secondary analysis, we also adjusted for bone pain. RESULTS: During follow-up, 88 (38%) patients had an SRE and 198 (85%) died. After adjusting for risk factors, SRE was associated with increased mortality (hazard ratio (HR)=1.67; 95% confidence interval (CI) 1.22-2.30; P=0.001). When bone pain was added to the model, the association of SREs and OS was attenuated, but remained significant (HR=1.42; 95% CI 1.01-1.99; P=0.042). CONCLUSIONS: SREs are associated with increased mortality in men with bone mCRPC. Further studies on the impact of preventing SREs to increase survival are warranted. PMID- 27377208 TI - Growth and fertilization of porcine fetal oocytes grafted under the renal capsules of nude mice. AB - The fetal ovary contains a larger pool of oocytes than the adult ovary, but utilization of the fetal oocytes of large animals has hardly been examined. In this study, we investigated the developmental competence of oocytes grown in host mice harboring ovarian grafts obtained from fetal pigs. Ovarian fragments from fetuses at 55, 70, and 90 days postartificial insemination (dpi) were grafted into ovariectomized nude mice (Crlj:CD1-Foxn1(nu); 55-, 70- and 90-dpi groups, respectively). For comparison, ovarian fragments from 20-day postpartum (dpp) piglets were also grafted (20-dpp group). About 60 days after detection of vaginal opening, the mice were given 62.5 U/mL porcine FSH for 13 days by infusion to enhance their follicular development. In the fetal ovaries before grafting, the percentage of germ cells in primordial follicles (termed primordial oocytes) relative to the total number of germ cells was 0.06% at 55 dpi, 2.4% at 70 dpi, and 7.2% at 90 dpi, but the majority was contained within egg nests. At 20 dpp, primordial oocytes accounted for 91.7% of the total number of germ cells and the rest were mostly in primary follicles. After FSH stimulation of host mice, formation of antral follicles was promoted in the grafts of the 70- and 90 dpi groups as well as the 20-dpp group, but a very small number of antral follicles developed in the 55-dpi group consistent with the lowest (P < 0.05) levels of circulating inhibin in that group. The mean number of full-sized oocytes with meiotic competence recovered per mouse was 6.0 in the 70-dpi, 18.0 in the 90-dpi, and 21.2 in the 20-dpp groups, whereas virtually no oocytes were recovered from mice in the 55-dpi group. Moreover, the mature oocytes in the 70- and 90-dpi groups were fertilized in vitro, as shown by formation of male and female pronuclei, but the percentage of oocytes penetrated by sperm was low in the 70- (49%) and 90-dpi (29%) groups as compared with the 20-dpp group (88%). These results clearly indicate that porcine fetal ovaries during the late pregnancy period are able to grow and produce oocytes with fertilization ability after being grafted into nude mice. The presence of primordial follicles is likely to be associated with the ability of fetal ovaries to produce antral follicles after xenografting. PMID- 27377209 TI - Effect of medium variations (zinc supplementation during oocyte maturation, perifertilization pH, and embryo culture protein source) on equine embryo development after intracytoplasmic sperm injection. AB - Prospective studies were conducted to help define procedural factors affecting in vitro embryo production via intracytoplasmic sperm injection (ICSI) of equine oocytes. In experiment 1, use of 10% fetal bovine serum as a protein source in embryo culture medium resulted in a higher blastocyst rate than did use of a combination of 3% fetal bovine serum, 3% equine preovulatory follicular fluid, and 4% human serum substitute (37% vs. 15%, respectively, P < 0.05). In experiment 2, the effect of zinc supplementation (0, 0.5, 1, or 1.5 MUg/mL) during IVM was examined. There were no significant differences in rates of cleavage or blastocyst development (20%-31%). However, the proportion of blastocysts that developed on Day 7 for the added-zinc treatments was significantly higher than that for the control treatment (45% vs. 8%). In experiment 3, we tested whether use of high-pH medium (pH 8.0-8.4) during ICSI procedures would improve blastocyst rate when sperm with low cleavage rates after ICSI was used. When high-pH conditions were used for sperm preparation and also for the first 2 hours of incubation of injected oocytes after ICSI, the cleavage rate was unaffected but no blastocysts developed (0% vs. 24% for control). When high-pH conditions were used for sperm preparation only, the blastocyst rate was 37%. This was repeated using sperm from a second stallion; there was no significant difference in cleavage or blastocyst rates between sperm preparation in high pH vs. control medium. These findings add to our knowledge of factors affecting in vitro production of equine embryos. PMID- 27377210 TI - A 31-kDa seminal plasma heparin-binding protein reduces cold shock stress during cryopreservation of cross-bred cattle bull semen. AB - In the present study, a 31-kDa protein, purified from cattle bull seminal plasma heparin-binding proteins (SP-HBP), was characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis and mass spectrometry. Raw semen of six cross bred bulls was treated with 31-kDa HBP before cryopreservation to observe its effect on motility, viability, hypo-osmotic swelling test, acrosome integrity, in vitro capacitation/acrosome reaction, and oxidative stress at pre-freeze and frozen-thawed phases of cryopreservation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of 31-kDa protein eluted and purified from SP-HBP (separated on acrylamide gels) resulted in a single band of 40 kDa. In matrix-assisted laser desorption/ionization-time of flight analysis, 12 peptides were identified with matching significantly (P < 0.05) to interlukin-6 of bovine with a top score of 55. Addition of 25 MUg/mL of fluorescein isothiocyanate-conjugated 31-kDa protein to raw semen and incubation at 37 degrees C for 20 minutes before cryopreservation resulted in its binding mainly to head region. Treatment of semen with 31-kDa HBP resulted in a significant (P < 0.05) average increase of 9.2%, 6.8%, and 11.7% and 5.5%, 6.5%, and 11.0% in motile, viable, hypo-osmotic swelling-responsive spermatozoa in six bulls at pre-freeze and frozen-thawed phases of cryopreservation, respectively. Percentage of spermatozoa with intact acrosomes nonsignificantly enhanced in the semen treated with 31-kDa HBP at both phases of cryopreservation. An average nonsignificant increase of 3.1% in in vitro capacitated and acrosome-reacted spermatozoa was obtained in semen supplemented with 31-kDa HBP. Addition of 31-kDa HBP also nonsignificantly reduced Malonadialdehyde (MDA) level by 10.7 and 19.3 MUM/10(9) spermatozoa in prefrozen and frozen-thawed semen, respectively. The results obtained here indicate to conclude that treatment of cross-bred cattle bull semen with 31-kDa HBP protects the spermatozoa from cold shock effect by coating the sperm surface. PMID- 27377212 TI - Association between acetylcholinesterase inhibitors and risk of stroke in patients with dementia. AB - Patients with dementia are at increased risk of stroke. Acetylcholinesterase inhibitors (AChEIs) have endothelial function protection effects and anti inflammatory properties. We investigated the ischemic stroke risk in AChEIs use in dementia patients without stroke history. Using Taiwan National Health Insurance Database from 1999 to 2008, 37,352 dementia patients over 50 years old without stroke history were eligible. The results were analyzed by propensity score-matched Cox proportional hazard models with competing risk adjustment. AChEIs users had lower incidence of ischemic stroke (160.3/10,000 person-years), compared to the propensity score-matched reference (240.8/10,000 person-years). The adjusted hazard ratio for ischemic stroke based on propensity score-matched Cox proportional hazard model was 0.508 (95% confidence interval, 0.434-0.594; P < 0.001). There was no significant difference in all-cause mortality between AChEIs users and nonusers. In conclusion, among dementia patients without previous ischemic stroke history, AChEIs treatment was associated with a decreased risk of ischemic stroke but not greater survival. PMID- 27377213 TI - Surface effects of vapour-liquid-solid driven Bi surface droplets formed during molecular-beam-epitaxy of GaAsBi. AB - Herein we investigate a (001)-oriented GaAs1-xBix/GaAs structure possessing Bi surface droplets capable of catalysing the formation of nanostructures during Bi rich growth, through the vapour-liquid-solid mechanism. Specifically, self aligned "nanotracks" are found to exist trailing the Bi droplets on the sample surface. Through cross-sectional high-resolution transmission electron microscopy the nanotracks are revealed to in fact be elevated above surface by the formation of a subsurface planar nanowire, a structure initiated mid-way through the molecular-beam-epitaxy growth and embedded into the epilayer, via epitaxial overgrowth. Electron microscopy studies also yield the morphological, structural, and chemical properties of the nanostructures. Through a combination of Bi determination methods the compositional profile of the film is shown to be graded and inhomogeneous. Furthermore, the coherent and pure zincblende phase property of the film is detailed. Optical characterisation of features on the sample surface is carried out using polarised micro-Raman and micro-photoluminescence spectroscopies. The important light producing properties of the surface nanostructures are investigated through pump intensity-dependent micro-PL measurements, whereby relatively large local inhomogeneities are revealed to exist on the epitaxial surface for important optical parameters. We conclude that such surface effects must be considered when designing and fabricating optical devices based on GaAsBi alloys. PMID- 27377214 TI - [Expression of miR-22 and miR-150 in type 1 diabetes mellitus: Possible relationship with autoimmunity and clinical characteristics]. AB - BACKGROUND AND OBJECTIVE: Type 1 diabetes (T1D) is an autoimmune disease of complex aetiology. Several microRNAs (miR) have been linked to the pathogenesis of autoimmune diseases. To analyze the possible association of miR-22 and miR-150 with autoimmunity and clinical severity of T1D. PATIENTS AND METHODS: The study was performed in peripheral blood mononuclear cells of 20 patients with T1D and 20 control subjects. The expression of miR-22 and miR-150 was performed in peripheral blood mononuclear cells using TaqMan probes to different glucose concentrations (baseline, 11mm, 25mm). RESULTS: Our results suggest that the expression of miR-22 is increased in T1D patients compared to the controls. This effect was observed in baseline glucose conditions and decreased in 11 and 25mM of glucose. The expression of miR-150 was lower in T1D patients versus the controls. There was no correlation between the autoimmune profile and the two studied miRNAs. miR-22 (baseline condition) and miR-150 (11mM condition) or the ketoacidosis component. CONCLUSION: miR-22 and 150 were not associated with the autoimmune component present in T1D patients. PMID- 27377215 TI - [Chronic bacterial prostatitis. Clinical and microbiological study of 332 cases]. AB - BACKGROUND AND OBJECTIVE: Chronic bacterial prostatitis (CBP) is characterized by long-lasting symptoms, frequently associated with psychosomatic disorders. The objective of the study was to study PCB in our environment clinically and microbiologically. METHODS: Between January 2013 and December 2014 761 patients with suspected CBP were studied. Of these patients 332 (43.6%) underwent a complete microbiological study and the major clinical signs and symptoms were collected. RESULTS: Eighteen point four percent of patients were diagnosed microbiologically with CBP, Enterococcus faecalis being the main aetiologic agent (37.7%), followed by Escherichia coli (22.2%). Ninety-six point seven percent of the CBP had positive semen cultures, while only 22.9% had positive urine post semen cultures. Data of sensitivity, specificity, positive predictive value and negative predictive value of semen were 96.7%, 95.9%, 84.3% and 99.3%, respectively and urine post-semen 22.9%, 99.3%, 87.5% and 85.1%, respectively. Testicular perineum pain (44.3%), ejaculatory discomfort (27.9%) and haemospermia (26.2%) were highlighted as the patients' main clinical manifestations. CONCLUSIONS: Fractionated culture for the microbiological diagnosis of CBP could be simplified by the culture of urine pre-semen and semen, without the need for the culture of urine post-semen. The main aetiologic agent of CBP in our media was Enterococcus faecalis, followed by Escherichia coli. PMID- 27377216 TI - Filtration markers and determination methods for the assessment of kidney function. AB - Estimation of renal function is crucial for a number of clinical situations. Endogenous markers such as creatinine, as well as several exogenous agents including inulin, 99mTc-DTPA and iothalamate are used for evaluation of kidney function. At present, new generation filtration markers and determination methods based on organic fluorescent dyes and fluorescent detection technique are developed. This review gives an overview of filtration markers and clearance methods for the assessment of kidney function. New filtration markers and transcutaneous measurement of renal function are described. Problems and issues relating to the reabsorption or secretion of each of markers and the applicability of methods are also discussed. PMID- 27377217 TI - The flavonoid fisetin as an anticancer agent targeting the growth signaling pathways. AB - Epidemiological studies show that consumption of diets rich in fruits and vegetables is associated with lower risks of cancer. This evidence has kindled interest into research on bioactive food components and has till date resulted in the identification of many compounds with cancer preventive and therapeutic potential. Among such compounds is fisetin (3,7,3,4-tetrahydroxyflavone), a flavonol that is commonly found in many fruits and vegetables such as apples, persimmons, grapes, kiwis, strawberries, onions and cucumbers. Fisetin has been shown to inhibit or retard the growth of various cancer cells in culture and implanted tumors in vivo. Fisetin targets many components of intracellular signaling pathways including regulators of cell survival and apoptosis, tumor angiogenic and metastatic switches by modulating a distinct set of upstream kinases, transcription factors and their regulators. Current evidence supports the idea that fisetin is a promising agent for cancer treatment. This review summarizes reported anticancer effects of fisetin, and re-emphasizes its potential therapeutic role in the treatment of cancer. PMID- 27377218 TI - Use of a novel pulmonary artery cannula to provide extracorporeal membrane oxygenation as a bridge to lung transplantation. PMID- 27377219 TI - Roles of inflammation and apoptosis in experimental brain death-induced right ventricular failure. AB - BACKGROUND: Right ventricular (RV) dysfunction remains the leading cause of early death after cardiac transplantation. Methylprednisolone is used to improve graft quality; however, evidence for that remains empirical. We sought to determine whether methylprednisolone, acting on inflammation and apoptosis, might prevent brain death-induced RV dysfunction. METHODS: After randomization to placebo (n = 11) or to methylprednisolone (n = 8; 15 mg/kg), 19 pigs were assigned to a brain death procedure. The animals underwent hemodynamic evaluation at 1 and 5 hours after Cushing reflex (i.e., hypertension and bradycardia). The animals euthanized, and myocardial tissue was sampled. This was repeated in a control group (n = 8). RESULTS: At 5 hours after the Cushing reflex, brain death resulted in increased pulmonary artery pressure (27 +/- 2 vs 18 +/- 1 mm Hg) and in a 30% decreased ratio of end-systolic to pulmonary arterial elastances (Ees/Ea). Cardiac output and right atrial pressure did not change. This was prevented by methylprednisolone. Brain death-induced RV dysfunction was associated with increased RV expression of heme oxygenase-1, interleukin (IL)-6, IL-10, IL-1beta, tumor necrosis factor (TNF)-alpha, IL-1 receptor-like (ST)-2, signal transducer and activator of transcription-3, intercellular adhesion molecules-1 and -2, vascular cell adhesion molecule-1, and neutrophil infiltration, whereas IL-33 expression decreased. RV apoptosis was confirmed by terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling staining. Methylprednisolone pre-treatment prevented RV-arterial uncoupling and decreased RV expression of TNF-alpha, IL-1 receptor-like-2, intercellular adhesion molecule 1, vascular cell adhesion molecule-1, and neutrophil infiltration. RV Ees/Ea was inversely correlated to RV TNF-alpha and IL-6 expression. CONCLUSIONS: Brain death-induced RV dysfunction is associated with RV activation of inflammation and apoptosis and is partly limited by methylprednisolone. PMID- 27377220 TI - Lung transplantation in the spotlight: Reasons for high-cost procedures. AB - BACKGROUND: Hospital treatment costs of lung transplantation are insufficiently analyzed. Accordingly, it remains unknown, whether current Diagnosis Related Groups, merely accounting for 3 ventilation time intervals and length of hospital stay, reproduce costs properly, even when an increasing number of complex recipients are treated. Therefore, in this cost determination study, actual costs were calculated and cost drivers identified. METHODS: A standardized microcosting approach allowed for individual cost calculations in 780 lung transplant patients taken care of at Hannover Medical School and University of Munich from 2009 to 2013. A generalized linear model facilitated the determination of characteristics predictive for inpatient costs. RESULTS: Lung transplantation costs varied substantially by major diagnosis, with a mean of ?85,946 (median ?52,938 +/- 3,081). Length of stay and ventilation time properly reproduced costs in many cases. However, complications requiring prolonged ventilation or reinterventions were identified as additional significant cost drivers, responsible for high costs. CONCLUSIONS: Diagnosis Related Groups properly reproduce actual lung transplantation costs in straightforward cases, but costs in complex cases may remain underestimated. Improved grouping should consider major diagnosis, a higher gradation of ventilation time, and the number of reinterventions to allow for more reasonable reimbursement. PMID- 27377221 TI - Temporo-parietal connectivity uniquely predicts reading change from childhood to adolescence. AB - Previous research has shown that left posterior middle temporal gyrus (pMTG) is a core node in the semantic network, and cross-sectional studies have shown that activation in this region changes developmentally and is related to skill measured concurrently. However, it is not known how functional connectivity with this region changes developmentally, and whether functional connectivity is related to future gains in reading. We conducted a longitudinal functional magnetic resonance imaging (fMRI) study in 30 typically developing children (aged 8-15) to examine whether initial brain measures, including activation and connectivity, can predict future behavioral improvement in a semantic judgment task. Participants were scanned on entering the study (time 1, T1) and a follow up period of 2years (time 2, T2). Character pairs were arranged in a continuous variable according to association strength (i.e. strong versus weak), and participants were asked to determine if these visually presented pairs were related in meaning. Our results demonstrated greater developmental changes from time 1 to time 2 for weaker association pairs in the left pMTG for the children (aged 8-11) as compared to the adolescents (aged 12-15). Moreover, the results showed greater developmental changes from time 1 to time 2 for weaker association pairs in connectivity between the pMTG and inferior parietal lobule (IPL) for the children as compared to the adolescents. Furthermore, a hierarchical stepwise regression model revealed that connectivity between the pMTG and IPL in weak association pairs was uniquely predictive of behavioral improvement from time 1 to time 2 for the children, but not the adolescents. Taken together, the activation results suggest relatively rapid development before adolescence of semantic representations in the pMTG. Moreover, the connectivity results of pMTG with IPL tentatively suggest that early development of semantic representations may be facilitated by enhanced engagement of phonological short-term memory. PMID- 27377222 TI - A multi-time-point modality-agnostic patch-based method for lesion filling in multiple sclerosis. AB - Multiple sclerosis lesions influence the process of image analysis, leading to tissue segmentation problems and biased morphometric estimates. Existing techniques try to reduce this bias by filling all lesions as normal-appearing white matter on T1-weighted images, considering each time-point separately. However, due to lesion segmentation errors and the presence of structures adjacent to the lesions, such as the ventricles and deep grey matter nuclei, filling all lesions with white matter-like intensities introduces errors and artefacts. In this paper, we present a novel lesion filling strategy inspired by in-painting techniques used in computer graphics applications for image completion. The proposed technique uses a five-dimensional (5D), patch-based (multi-modality and multi-time-point), Non-Local Means algorithm that fills lesions with the most plausible texture. We demonstrate that this strategy introduces less bias, fewer artefacts and spurious edges than the current, publicly available techniques. The proposed method is modality-agnostic and can be applied to multiple time-points simultaneously. In addition, it preserves anatomical structures and signal-to-noise characteristics even when the lesions are neighbouring grey matter or cerebrospinal fluid, and avoids excess of blurring or rasterisation due to the choice of the segmentation plane, shape of the lesions, and their size and/or location. PMID- 27377223 TI - Curcumin has protective and antioxidant properties on bull spermatozoa subjected to induced oxidative stress. AB - Over the past decades, there has been an emphasis on assessment of the use of natural compounds in the prevention or repair of oxidative injury to spermatozoa. Curcumin (CUR) is a natural phenol with powerful antioxidant properties. The aim of the present study was to examine if CUR could reverse reactive oxygen species (ROS)-mediated alterations to the motility, viability and intracellular antioxidant profile of bull spermatozoa subjected to a prooxidant (i.e., ferrous ascorbate - FeAA). Spermatozoa were washed from recently collected semen samples, suspended in 2.9% sodium citrate and subjected to CUR treatment (5, 10, 25 and 50MUmol/L) in the presence or absence of FeAA (150MUmol/L FeSO4 and 750MUmol/L ascorbic acid) during a 6h in vitro culture. Spermatozoa motility characteristics were assessed using the SpermVision computer-aided spermatozoa analysis (CASA) system. Cell viability was examined with the metabolic activity (MTT) assay, ROS generation was quantified using luminometry and the nitroblue-tetrazolium (NBT) test was used to quantify the intracellular superoxide formation. Cell lysates were prepared at the end of the culture to assess the intracellular activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) as well as the concentrations of glutathione (GSH) and malondialdehyde (MDA). Treatment with FeAA led to a reduced spermatozoa motility (P<0.001), viability (P<0.001) and decreased the antioxidant characteristics of the samples (P<0.001) but increased the ROS generation (P<0.001), superoxide production (P<0.001) and lipid peroxidation (P<0.001). The CUR treatment led to a preservation of spermatozoa motion (P<0.001), mitochondrial activity (P<0.001) and antioxidant characteristics (P<0.05 with SOD and GSH; P<0.01 with CAT and GPx), revealing the concentration range of 25-50MUmol/L CUR to be the most effective for sustaining spermatozoa viability. Data from the present study suggest that CUR exhibits significant protective and ROS-scavenging characteristics which may prevent oxidative insults to spermatozoa and thus preserve the functional activity of male gametes. PMID- 27377224 TI - Lumbar Neuroforaminal Decompression with a Flexible Microblade Shaver System: Results of a Cadaveric Study. AB - BACKGROUND: The lumbar neural foraminal stenosis still is a challenging condition in minimally invasive spine surgery. Because of the anatomic situation a complete decompression of the nerve root often leads to a subtotal facetectomy associated with potential instability and the need for additional instrumentation of the decompressed segment. The iO-Flex system was introduced to address this problem by using a minimally invasive wire-guided microblade shaver to increase the neuroforaminal space by reducing the stenosis from intraforaminal while sparing bigger parts of the facet joint. In this study, we evaluated the feasibility and the surgical and radiological success in relation to the experience of the surgeon. METHODS: We performed decompression of the neuroforamen in 10 lumbar levels of 2 fresh-frozen human cadavers. Before and after decompression, we obtained high-resolution computed tomography data to evaluate the diameter of the neural foramen. RESULTS: The mean foraminal width (7.88-10.94 mm, P < 0.0001) and area (123.27-149.18 mm2, P < 0.003) increased significantly after the decompression, whereas the facet joints area (131.9-107.51 mm2, P < 0.005) and width (16.4-13.75 mm, P < 0.001) indeed decreased significantly but with an overall reduction of facet joint width by 16% and facet joint area by 18%. No complications such as nerve root damages or dural tears were observed. CONCLUSIONS: The flexible micro blade shaver system is feasible with a steep learning curve and achieves sufficient decompression of the neuroforamen in this cadaveric study. PMID- 27377225 TI - Functional Hemispherectomy for Refractory Status Epilepticus in 2 Adults. AB - BACKGROUND: Status epilepticus (SE) is a medical emergency, as deleterious long term effects are well known. Medically induced burst suppression is often required if first-line and second-line treatments fail. Surgical intervention can be considered in some patients after prolonged treatment failure of medically induced coma. Multiple surgical options for terminating SE have been demonstrated in the literature, with only 2 reports including hemispherectomy in adults. CASE DESCRIPTION: We present 2 cases of adults with refractory SE who failed more conservative medical/surgical treatment but responded to functional hemispherectomy. Pertinent electroencephalography and imaging findings are discussed. In addition, all previously published pediatric and adult cases are briefly reviewed. CONCLUSIONS: Functional hemispherectomy can be considered in patients, including adults, with super-refractory SE and diffuse hemispheric onset. We report acceptable outcomes and quality of life in our 2 patients. PMID- 27377226 TI - Radial Artery Graft Bypass with Endovascular Trapping of the Internal Carotid Artery for Recurrent Carotid Cavernous Fistula: Different Surgical Fields, Different Surgical Considerations. AB - BACKGROUND: Venous infarction in the brainstem caused by venous congestion is an extremely rare complication of traumatic carotid cavernous fistulas (CCFs). This condition requires immediate treatment and a multimodal treatment strategy is needed to prevent recurrence. CASE DESCRIPTION: A 24-year-old man presented with exophthalmos and chemosis after a bicycle accident. Cerebral angiography showed an engorged right superior ophthalmic vein and a right carotid cavernous fistula. Transvenous coil embolization was successfully performed without severe complications. Two months later, a decline in mental status occurred. Follow-up angiography showed recanalization of the CCF. The patient underwent radial artery graft bypass surgery combined with endovascular trapping of the internal carotid artery. Sylvian veins and other cortical veins became intraoperatively arterialized and we observed marked brain edema after high-flow CCF. After surgery, the patient's mental status recovered and angiography showed good patency of the bypass graft and complete obliteration of the recurrent CCF. CONCLUSIONS: To ensure prevention of recurrent CCF, internal carotid artery trapping combined with high-flow bypass surgery can be a good salvage treatment for urgent cases in which an endovascular approach already failed. PMID- 27377227 TI - Acute typhlitis caused by a caecal faecolith. AB - Isolated acute typhlitis caused by a caecal faecolith is extremely rare. Hereby we report such a case. A 30-year-old man presented clinically as acute appendicitis. During open surgery, an inflamed caecal mass was found. A limited colectomy including the mass and grossly health margins was performed. Histopathological examination confirmed that acute typhlitis was caused by an impacted caecal faecolith. The appendix was normal. Faecolith is an extremely rare cause of acute inflammation of the caecum presenting as a mass which is usually treated by limited right hemicolectomy. PMID- 27377228 TI - Strengthening aerobic granule by salt precipitation. AB - Structural stability of aerobic granules is generally poor during long-term operation. This study precipitated seven salts inside aerobic granules using supersaturated solutions of (NH4)3PO4, CaCO3, CaSO4, MgCO3, Mg3(PO4)2, Ca3(PO4)2 or SiO2 to enhance their structural stability. All precipitated granules have higher interior strength at ultrasonic field and reveal minimal loss in organic matter degradation capability at 160-d sequential batch reactor tests. The strength enhancement followed: Mg3(PO4)2=CaSO4>SiO2>(NH4)3PO4>MgCO3>CaCO3=Ca3(PO4)2>original. Also, the intra granular solution environment can be buffered by the precipitate MgCO3 to make the aerobic granules capable of degradation of organic matters at pH 3. Salt precipitation is confirmed a simple and cost-effective modification method to extend the applicability of aerobic granules for wastewater treatments. PMID- 27377229 TI - Preclinical evaluation of three polyspecific antivenoms against the venom of Echis ocellatus: Neutralization of toxic activities and antivenomics. AB - Snakebite envenoming has a heavy burden in the public health in sub-Saharan Africa. The viperid species Echis ocellatus (carpet viper or saw-scaled viper) is the medically most important snake in the savannahs of western sub-Saharan Africa. Several antivenoms are being distributed and used in this region for the treatment of envenomings by E. ocellatus, but the preclinical efficacy of some of these antivenoms has not been assessed. The present study evaluated the preclinical efficacy against E. ocellatus venom of three polyspecific antivenoms: (a) Snake Venom Antiserum (Pan Africa), manufactured by Premium Serums and Vaccines (India); (b) Snake Venom Antiserum (Africa), manufactured by VINS Bioproducts (India); and (c) Antivipmyn((r)) Africa, manufactured by Instituto Bioclon (Mexico). Antivenomics analysis revealed the ability of the three antivenoms to immunocapture the majority of components of the venoms of E. ocellatus from Cameroon, Nigeria and Mali, although their maximal immunocapturing capability varied. Bioclon and Premium Serums antivenoms were effective in the neutralization of lethal, hemorrhagic and in vitro coagulant activities of the venom of E. ocellatus from Cameroon, albeit with different potencies. VINS antivenom neutralized hemorrhagic activity of this venom, but failed to neutralize lethality at the highest antivenom dose tested, and had a low neutralizing efficacy against in vitro coagulant effect. PMID- 27377231 TI - Reply to Letter to the Editor. PMID- 27377230 TI - Rapid and selective detection of experimental snake envenomation - Use of gold nanoparticle based lateral flow assay. AB - In this study, we have developed a gold nanoparticle based simple, rapid lateral flow assay (LFA) for detection of Indian Cobra venom (CV) and Russell's viper venom (RV). Presently, there is no rapid, reliable, and field diagnostic test available in India, where snake bite cases are rampant. Therefore, this test has an immense potential from the public health point of view. The test is based on the principle of the paper immunochromatography assay for detection of two snake venom species using polyvalent antisnake venom antibodies (ASVA) raised in equines and species-specific antibodies (SSAbs) against venoms raised in rabbits for conjugation and impregnation respectively. The developed, snake envenomation detection immunoassay (SEDIA) was rapid, selective, and sensitive to detect venom concentrations up to 0.1 ng/ml. The functionality of SEDIA strips was confirmed by experimental envenomation in mice and the results obtained were specific for the corresponding venom. The SEDIA has a potential to be a field diagnostic test to detect snake envenomation and assist in saving lives of snakebite victims. PMID- 27377232 TI - Effects of Radioactive Iodine Ablation Therapy on Voice Quality. AB - OBJECTIVE: The goal of this study was to evaluate the effects of radioactive iodine ablation therapy on voice quality of patients diagnosed with well differentiated thyroid carcinoma. METHODS: We enrolled 36 patients who underwent total or subtotal thyroidectomy due to well-differentiated thyroid carcinoma. Voice recordings from patients were analyzed for acoustic and aerodynamic voice. The Voice Handicap Index-10 was used for subjective analysis. The control group consisted of 36 healthy participants. Results taken before and after therapy were compared statistically. RESULTS: There were no differences in the results taken before and after therapy for the radioactive iodine ablation group. The Voice Handicap Index-10 results did not differ between groups before and after therapy. CONCLUSION: Radioactive iodine ablation therapy has no effect on voice quality objectively or subjectively. PMID- 27377233 TI - Endolymph movement visualized with light sheet fluorescence microscopy in an acute hydrops model. AB - There are a variety of techniques available to investigate endolymph dynamics, primarily seeking to understand the cause of endolymphatic hydrops. Here we have taken the novel approach of injecting, via a glass micropipette, fluorescein isothiocyanate-dextran (FITC-dex) and artificial endolymph into scala media of anaesthetized guinea pigs, with subsequent imaging of the inner ear using Light Sheet Fluorescence Microscopy (LSFM) as a means to obtain highly resolved 3D visualization of fluid movements. Our results demonstrate endolymph movement into the utricle, semicircular canals and endolymphatic duct and sac when more than 2.5 MUl of fluid had been injected into scala media, with no apparent movement of fluid into the perilymphatic compartments. There was no movement of endolymph into these compartments when less than 2.5 MUl was injected. The remarkable uptake of the FITC-dex into the endolymphatic duct, including an absorption into the periductal channels surrounding the endolymphatic duct, highlights the functional role this structure plays in endolymph volume regulation. PMID- 27377234 TI - An assessment of formaldehyde emissions from laminate flooring manufactured in China. AB - Formaldehyde emissions from two laminate flooring products, labeled as California Air Resources Board (CARB) compliant, were evaluated. Passive 24-hr samples (n = 79) and real-time measurements were collected following installation and removal of the products in two rooms of similar size. Mean formaldehyde concentrations following installation were 0.038 and 0.022 ppm for Products 1 and 2 respectively, and 7 days after flooring removal the concentrations returned to background pre-installation levels. Both products were also evaluated in a small chamber (ASTM D6007) using Deconstructive (de-laminated product) and Non Deconstructive (intact product) methods. Deconstructive testing showed that Product 1 exceeded the applicable CARB emission standard by 4-fold, while Product 2 was equivalent to the standard. Non-Deconstructive measurements were far below the Deconstructive results and were used to predict 24-hr steady-state room air concentrations. Based on the products that we tested (one of which was found to not be compliant with the CARB standard), the airborne formaldehyde concentrations measured following installation in a real-world setting would not be expected to elicit adverse acute health effects. PMID- 27377236 TI - A new species of Dactylogyrus (Monogenea: Dactylogyridae) parasitic on an endangered freshwater fish, Rhodeus atremius atremius, endemic to Japan. AB - A new dactylogyrid monogenean Dactylogyrus bicorniculus sp. nov. is described from the gills of the kazetoge bitterling, Rhodeus atremius atremius (Jordan and Thompson, 1914), an endemic species in Japan, from Saga Prefecture, northern Kyushu. D. bicorniculus sp. nov. resembles Dactylogyrus bicornis Malevitskaja, 1941 and Dactylogyrus lophogonus Zhang and Ji, 1980 because they have two common features, a large V-shaped ventral bar and well-developed second marginal hooks. However, the new species is distinguished from these congeners by a shorter penis and an accessory piece. A phylogenetic analysis of 28S rDNA shows that D. bicorniculus sp. nov. is a basal species with the T-shaped ventral bar in the genus. The new species has strict host-specificity to R. a. atremius, one of the endangered freshwater fishes in Japan, and may face the danger of co-extinction with its host. PMID- 27377235 TI - N-linked glycosylation of Kv1.2 voltage-gated potassium channel facilitates cell surface expression and enhances the stability of internalized channels. AB - KEY POINTS: Kv1.2 and related voltage-gated potassium channels have a highly conserved N-linked glycosylation site in the first extracellular loop, with complex glycosylation in COS-7 cells similar to endogenous Kv1.2 glycosylation in hippocampal neurons. COS-7 cells expressing Kv1.2 show a crucial role of this N linked glycosylation in the forward trafficking of Kv1.2 to the cell membrane. Although both wild-type and non-glycosylated mutant Kv1.2 channels that have reached the cell membrane are internalized at a comparable rate, mutant channels are degraded at a faster rate. Treatment of wild-type Kv1.2 channels on the cell surface with glycosidase to remove sialic acids also results in the faster degradation of internalized channels. Glycosylation of Kv1.2 is important with respect to facilitating trafficking to the cell membrane and enhancing the stability of channels that have reached the cell membrane. ABSTRACT: Studies in cultured hippocampal neurons and the COS-7 cell line demonstrate important roles for N-linked glycosylation of Kv1.2 channels in forward trafficking and protein degradation. Kv1.2 channels can contain complex N-linked glycans, which facilitate cell surface expression of the channels. Additionally, the protein stability of cell surface-expressed Kv1.2 channels is affected by glycosylation via differences in the degradation of internalized channels. The present study reveals the importance of N-linked complex glycosylation in boosting Kv1.2 channel density. Notably, sialic acids at the terminal sugar branches play an important role in dampening the degradation of Kv1.2 internalized from the cell membrane to promote its stability. PMID- 27377237 TI - Selective and Efficient Reduction of Carbon Dioxide to Carbon Monoxide on Oxide Derived Nanostructured Silver Electrocatalysts. AB - In this work, the selective electrocatalytic reduction of carbon dioxide to carbon monoxide on oxide-derived silver electrocatalysts is presented. By a simple synthesis technique, the overall high faradaic efficiency for CO production on the oxide-derived Ag was shifted by more than 400 mV towards a lower overpotential compared to that of untreated Ag. Notably, the Ag resulting from Ag oxide is capable of electrochemically reducing CO2 to CO with approximately 80 % catalytic selectivity at a moderate overpotential of 0.49 V, which is much higher than that (ca. 4 %) of untreated Ag under identical conditions. Electrokinetic studies show that the improved catalytic activity is ascribed to the enhanced stabilization of COOH(.) intermediate. Furthermore, highly nanostructured Ag is likely able to create a high local pH near the catalyst surface, which may also facilitate the catalytic activity for the reduction of CO2 with suppressed H2 evolution. PMID- 27377238 TI - Sound Body Sound Mind? Physical Performance and the Risk of Dementia in the Oldest-Old: The 90+ Study. AB - OBJECTIVES: To examine the longitudinal association between physical performance and risk of dementia in individuals aged 90 and older without dementia. DESIGN: Population-based longitudinal study. SETTINGS: The 90+ Study, Laguna Woods, California. PARTICIPANTS: Men n = 176 and women n = 402 without dementia from The 90+ Study (n = 578, mean age 93.3). At baseline, 54% of participants were cognitively normal, and 46% had cognitive impairment, no dementia. MEASUREMENTS: Physical performance measures (4-m walk, 5 chair stands, handgrip, standing balance) were scored from 0 (unable to perform) to 4 (best performance). The outcome was dementia, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. Hazard ratios (HRs) for dementia in relation to baseline physical performance were estimated using Cox regression after adjustment for potential confounders. HRs and P-values for the overall Wald chi-square are reported to show the magnitude of each physical performance measure and the strength of the association between each measure and incident dementia. RESULTS: Poor physical performance in most measures was associated with greater risk of incident dementia over a mean follow-up of 2.6 years (range 0.6-9.0 years). After controlling for potential confounders, standing balance had the strongest association with incident dementia (HRs = 1.9 2.5, overall P = .02), followed by 4-m walk (HRs = 1.1-1.8, overall P = .04) and handgrip (HRs = 1.0-2.0, overall P = .03). The association with five chair stands was not significant. In a subanalysis limited to cognitively normal participants, HRs were attenuated, but most remained in the same direction. CONCLUSION: Poor physical performance is associated with risk of developing dementia over an average 2.6-year follow-up in the oldest-old, indicating that poor physical performance may be an early sign of late-age dementia. PMID- 27377239 TI - Transoral robotic surgery in the seated position: Rethinking our operative approach. AB - OBJECTIVES/HYPOTHESIS: Transoral surgery (TOS) is commonly performed in a supine patient with an oral retractor. Paradoxically, this strategy can create difficulty with visualizing and accessing pathology at the base of tongue, inferior pharynx, and larynx. We investigate the feasibility of TOS with the patient in the seated position. STUDY DESIGN: Pilot study. METHODS: TOS utilizing the da Vinci Robotic Surgical Xi and Si systems (Intuitive Surgical, Sunnyvale, CA) was performed on a fresh cadaver placed in both the traditional supine position and the seated position. Transoral robotic surgery (TORS) in the seated position was then performed on two patients for a supraglottic laryngectomy and a hypopharyngeal carcinoma resection. RESULTS: Visualization of the entire upper aerodigestive tract was possible in the cadaver and two patients in the seated position. The Si was superior for docking, instrumentation, and assistant access. The minimum operating table height is critical for successful access. Advantages of this position included increased posterior airway/operative space by approximately 2 cm, ability to manipulate the surgical field (nonrigid retraction), and improved visualization. Surgical procedures were completed in comparable times compared with standard TORS procedures. There were no complications related to seated TORS. CONCLUSIONS: TORS in the seated position was both safe and effective in this pilot study. It allows the surgeon to optimally operate in the inferior pharynx and larynx without the limitation of line of site access and visualization. A paradigm shift in patient positioning during TOS may allow improved surgical access and even greater patient candidacy. Further clinical investigation into this technique is warranted. LEVEL OF EVIDENCE: NA Laryngoscope, 127:122-126, 2017. PMID- 27377240 TI - IIAM (important information about me): a patient portability profile app for adults, children and families with neurodevelopmental disabilities. AB - PURPOSE: To describe the development of important information about me (IIAM), an application (app) used to communicate and organize healthcare information for people with neurodevelopmental disabilities (NDD). METHODS: Prior to the development of IIAM version 1.0, households with NDD were selected to participate in a focus group. Respondents (n = 7) were parents of children with NDD. Participants were asked to use a beta version for at least 2 months in day-to-day applications and to complete a questionnaire at the end of the trial. RESULTS: Over half (57%) of the participants found the beta version to be useful. The greatest limitation in usability was the child's age and literacy level. All participants found the app to be visually appealing and easy to navigate. IIAM was commonly used to communicate information to caregivers, and to facilitate quality interactions between the child and others. CONCLUSION: Mobile technology has become ubiquitous and has emerged as an important tool in healthcare. New applications could potentially promote accessible, cost-effective and self managed interventions for the disability community. IIAM is a user-friendly, well accepted and useful app for people with NDD. The focus group feedback elicited from the beta testing was used to develop the IIAM app version 1.0. However, the sample size in this initial feasibility study is small, and warrants a prospective study that evaluates the overall benefits of this app in improving quality of life and helping individuals with developmental disabilities manage their day-to-day activities. Implications for Rehabilitation Mobile technology has been more ubiquitous in health care and has emerged as a tool in communicating healthcare needs. New applications could potentially promote accessible, cost-effective and self-managed interventions for the disability community. IIAM (important information about me) is a new iOS application that enables adults and children with neurodevelopmental disabilities to organize their medical records, advocate for their healthcare needs, and help overcome communication and time limitations with health professionals and caregivers. PMID- 27377241 TI - The impact of the introduction of a palliative Macmillan consultant radiographer at one UK cancer centre. AB - OBJECTIVE: The UK radiotherapy (RT) workforce needs novel strategies to manage increasing demand. The appointment of a palliative RT (PRT) consultant radiographer (CR) offers a potential solution to enhance patient pathways providing timely RT. This article examined the impact of one such appointment. METHODS: Two prospective audits were completed 1 year apart. All patients receiving PRT for bone metastases between 01/01/2014-31/03/2014 (Audit 1) and 01/01/2015-31/01/2015 (Audit 2) were included. Data collected included demographics, treatment site, dose, fractionation, treatment indication and professionals who planned the PRT. The patient pathway from decision to treat (DTT) to commencement of PRT was scrutinized. RESULTS: 97 patients were identified for Audit 1 and 87 patients for Audit 2. Demographics were similar. Figures relate to Audit 1 and in brackets Audit 2. Indications for treatment: pain 55% (61%), metastatic spinal cord compression 41% (38%) and other neurological symptoms 4% (1%). The CR independently planned 13% (60%), being supervised for 36% (3%). Consultant clinical oncologists planned 43% (31%), with 7% (6%) planned by specialist registrars (SpRs). The pathway was enhanced in Audit 2, with 85% of patients treated within 14 days compared with 73% of patients treated in Audit 1. CONCLUSION: A CR has the potential to impact on the patient pathway, enabling quicker times from DTT to treatment. Continued audit of the role is required to ensure that it complements SpR training. ADVANCES IN KNOWLEDGE: Increasing longevity and improved systemic therapies have led to greater numbers of patients living longer with metastatic disease. The appointment of a CR offers a potential solution to the capacity difficulties faced by UK RT services. PMID- 27377242 TI - Polydopamine-Functionalized Graphene Oxide Loaded with Gold Nanostars and Doxorubicin for Combined Photothermal and Chemotherapy of Metastatic Breast Cancer. AB - Breast cancer is the leading cancer type diagnosed in the female population, and cancer metastasis is the main reason for cancer-caused mortality. A novel nanoplatform is herein presented integrating polydopamine-functionalized nanosized reduced graphene oxide (NRGO), gold nanostars (GNS), and doxorubicin (DOX) (denoted as NRGO-GNS@DOX) for combinational treatment of metastatic breast cancer. Upon localized near infrared (NIR) laser irradiation, the NRGO-GNS@DOX nanocomposites induce significant cytotoxicity in 4T1 breast cancer cells due to a cumulative therapy effect of NRGO-GNS-elicited hyperthermia and DOX-induced cytotoxicity. Antitumor studies in orthotopic 4T1 breast tumor-bearing nude mice demonstrate that NRGO-GNS@DOX in combination with NIR laser irradiation inhibit the tumor growth and suppress the lung metastasis. Contribution of DOX-caused apoptosis of the cancer cells and hyperthermia-induced deconstruction of the tumor-associated blood vessels may account for the superior antitumor performance of the NRGO-GNS@DOX nanocomposites. These results imply a good potential of NRGO GNS@DOX for combined photothermal and chemotherapy of the metastatic cancer. PMID- 27377243 TI - Comparison of Two Risk Models in Predicting the Incidence of Contrast-Induced Nephropathy after Percutaneous Coronary Intervention. AB - OBJECTIVES: We sought to compare 2 contrast-induced nephropathy (CIN) risk prediction models in a validation cohort using a consensus definition. BACKGROUND: Contrast-induced nephropathy (CIN) is independently associated with mortality following percutaneous coronary intervention (PCI). Multiple prediction models for the development of CIN have been published using heterogeneous outcome definitions. METHODS: We analyzed 5,540 patients who underwent PCI from January 2005 to June 2012 at a single academic medical center. The primary outcome was development of CIN, defined as an increase in serum creatinine of >=0.5 mg/dl or a relative increase of >=25% from baseline. Receiver operator characteristic (ROC) curves were used to evaluate the discriminatory power of Mehran and WBH prediction models. RESULTS: The mean age of our cohort was 68 +/- 12 years. The mean baseline creatinine was 1.2 +/- 0.53 mg/dl (eGFR 73 +/- 27 ml/min). The mean contrast volume used was 212 +/- 92 ml. CIN occurred in 436 patients (7.9%). The Mehran risk score demonstrated better discrimination than the William Beaumont Hospital (WBH) risk score to predict the occurrence of CIN (c statistic: 0.82 vs. 0.73, respectively). Mortality at 30 days was approximately 8 times higher among patients with CIN as compared to those without (14.7% vs. 1.8% P < 0.01). CONCLUSIONS: In an independent validation cohort, the Mehran risk model demonstrates greater discriminatory power than the WBH model in predicting the incidence of CIN. Mortality was significantly higher in patients who developed CIN after PCI. PMID- 27377245 TI - Ion chromatography with the indirect ultraviolet detection of alkali metal ions and ammonium using imidazolium ionic liquid as ultraviolet absorption reagent and eluent. AB - Indirect ultraviolet detection was conducted in ultraviolet-absorption-agent added mobile phase to complete the detection of the absence of ultraviolet absorption functional group in analytes. Compared with precolumn derivatization or postcolumn derivatization, this method can be widely used, has the advantages of simple operation and good linear relationship. Chromatographic separation of Li(+) , Na(+) , K(+) , and NH4 (+) was performed on a carboxylic acid base cation exchange column using imidazolium ionic liquid/acid/organic solvent as the mobile phase, in which imidazolium ionic liquids acted as ultraviolet absorption reagent and eluting agent. The retention behaviors of four kinds of cations are discussed, and the mechanism of separation and detection are described. The main factors influencing the separation and detection were the background ultraviolet absorption reagent and the concentration of hydrogen ion in the ion chromatography-indirect ultraviolet detection. The successful separation and detection of Li(+) , Na(+) , K(+) , and NH4 (+) within 13 min was achieved using the selected chromatographic conditions, and the detection limits (S/N = 3) were 0.02, 0.11, 0.30, and 0.06 mg/L, respectively. A new separation and analysis method of alkali metal ions and ammonium by ion chromatography with indirect ultraviolet detection method was developed, and the application range of ionic liquid was expanded. PMID- 27377244 TI - Bile salt receptor complex activates a pathogenic type III secretion system. AB - Bile is an important component of the human gastrointestinal tract with an essential role in food absorption and antimicrobial activities. Enteric bacterial pathogens have developed strategies to sense bile as an environmental cue to regulate virulence genes during infection. We discovered that Vibrio parahaemolyticus VtrC, along with VtrA and VtrB, are required for activating the virulence type III secretion system 2 in response to bile salts. The VtrA/VtrC complex activates VtrB in the presence of bile salts. The crystal structure of the periplasmic domains of the VtrA/VtrC heterodimer reveals a beta-barrel with a hydrophobic inner chamber. A co-crystal structure of VtrA/VtrC with bile salt, along with biophysical and mutational analysis, demonstrates that the hydrophobic chamber binds bile salts and activates the virulence network. As part of a family of conserved signaling receptors, VtrA/VtrC provides structural and functional insights into the evolutionarily conserved mechanism used by bacteria to sense their environment. PMID- 27377246 TI - Megan King: A force to be reckoned with. PMID- 27377248 TI - Lysosome acidification by photoactivated nanoparticles restores autophagy under lipotoxicity. AB - In pancreatic beta-cells, liver hepatocytes, and cardiomyocytes, chronic exposure to high levels of fatty acids (lipotoxicity) inhibits autophagic flux and concomitantly decreases lysosomal acidity. Whether impaired lysosomal acidification is causally inhibiting autophagic flux and cellular functions could not, up to the present, be determined because of the lack of an approach to modify lysosomal acidity. To address this question, lysosome-localizing nanoparticles are described that, upon UV photoactivation, enable controlled acidification of impaired lysosomes. The photoactivatable, acidifying nanoparticles (paNPs) demonstrate lysosomal uptake in INS1 and mouse beta-cells. Photoactivation of paNPs in fatty acid-treated INS1 cells enhances lysosomal acidity and function while decreasing p62 and LC3-II levels, indicating rescue of autophagic flux upon acute lysosomal acidification. Furthermore, paNPs improve glucose-stimulated insulin secretion that is reduced under lipotoxicity in INS1 cells and mouse islets. These results establish a causative role for impaired lysosomal acidification in the deregulation of autophagy and beta-cell function under lipotoxicity. PMID- 27377247 TI - Chromatin assembly: Journey to the CENter of the chromosome. AB - All eukaryotic genomes are packaged into basic units of DNA wrapped around histone proteins called nucleosomes. The ability of histones to specify a variety of epigenetic states at defined chromatin domains is essential for cell survival. The most distinctive type of chromatin is found at centromeres, which are marked by the centromere-specific histone H3 variant CENP-A. Many of the factors that regulate CENP-A chromatin have been identified; however, our understanding of the mechanisms of centromeric nucleosome assembly, maintenance, and reorganization remains limited. This review discusses recent insights into these processes and draws parallels between centromeric and noncentromeric chromatin assembly mechanisms. PMID- 27377249 TI - The Sam68 nuclear body is composed of two RNase-sensitive substructures joined by the adaptor HNRNPL. AB - The mammalian cell nucleus contains membraneless suborganelles referred to as nuclear bodies (NBs). Some NBs are formed with an architectural RNA (arcRNA) as the structural core. Here, we searched for new NBs that are built on unidentified arcRNAs by screening for ribonuclease (RNase)-sensitive NBs using 32,651 fluorescently tagged human cDNA clones. We identified 32 tagged proteins that required RNA for their localization in distinct nuclear foci. Among them, seven RNA-binding proteins commonly localized in the Sam68 nuclear body (SNB), which was disrupted by RNase treatment. Knockdown of each SNB protein revealed that SNBs are composed of two distinct RNase-sensitive substructures. One substructure is present as a distinct NB, termed the DBC1 body, in certain conditions, and the more dynamic substructure including Sam68 joins to form the intact SNB. HNRNPL acts as the adaptor to combine the two substructures and form the intact SNB through the interaction of two sets of RNA recognition motifs with the putative arcRNAs in the respective substructures. PMID- 27377250 TI - A qualitative exploration of the work of embodiment in adolescent girls with obesity. AB - Social representations generally associate obesity, especially in adolescent girls, with sedentariness, lack of self-control and laziness. These girls thus have substantial problems of self-esteem. Dietary, lifestyle and behavioural approaches alone cannot address this issue, for they do not apprehend all of the complexity of obesity. This qualitative study is based on a dual observation: that the work performed by adolescents is unrecognized and that the body is not considered as a subject of analysis. It raises the question of the corporality of these teens through an original perspective: that of the perspective of their organization of actions on, to and by the body, in specific situations. The objective is to have access to the corporal experience of young girls with obesity, so that we can understand and support them better. The data come from semi-directive interviews with 10 adolescent girls with obesity. The content was analysed in terms of concepts of professional didactics (a branch of educational psychology) and enaction. Five situations were identified from these interviews: the first, shopping with friends, concerns actions by the subjects towards their bodies; the other four are enacted actions: conduct towards a normal-weight person, conduct in public transportation, performing physical activity, and eating. The results show the work of these young women with obesity, the means they mobilize to live in their bodies and their considerable efforts of embodiment. Recognition of this work should help to enhance their self-esteem. Treatment and support may take this dimension of work into account and help them to become aware of the efforts they make every day. PMID- 27377251 TI - The impact of rapid weight loss (4%) on leptin, adiponectin, and insulin resistance in elite adult free style wrestlers. AB - BACKGROUND: The effect of rapid weight loss program on adipocytokines is not yet clear. Therefore the aim of the present study was the effect of rapid weight loss (4%) on leptin, adiponectin, and insulin resistance in elite free style wrestlers. METHODS: For this purpose, fifteen young freestyle wrestlers (weight 67.6+/-0.8, BMI 22.5+/-0.21 kg/m2, body fat percent 6.12+/-0.18, waist to hip circumference ratio 0.82+/-0.08) in two weight categories (60 and 66 kg) were randomly selected. Caloric intake (mean 7 days measured by Food analyzer software) measured at 1 week before weight loss program by standard methods. Wrestlers performed a week rapid weight loss (average of 4% of body weight loss) protocol by caloric and water restriction by 60% (600-700 kcal per day), under the supervision of their coach. Anthropometric characteristics, leptin, adiponectin and insulin resistance were measured before and 12 and 36 hours after rapid weight loss program. RESULTS: Rapid weight loss program with 4% of weight loss had a significantly reduced impact on anthropometric factors; leptin level, insulin resistance, and increased beta cell function, while the changes of adiponectin were not significant after rapid weight loss. CONCLUSIONS: Findings of this study shows that rapid weight loss program significantly decreased leptin, L/A ratio and HOMA-IR, without significant changes on adiponectin levels. These changes may have harmful physiological effects on wrestlers' bodies but they can be useful to regulate of fatty acid, glucose metabolism, and insulin resistance. PMID- 27377252 TI - Effects of mental training on muscular force, hormonal and physiological changes in kickboxers. AB - BACKGROUND: The aim of the present study was to examine the effects of mental training on muscular force generation, hormonal alterations, and physiological adaptations in male trained kickboxers. METHODS: Fifty-three male trained kickboxers (24.2+/-4.4 years, 1.75+/-0.08 m and 70.4+/-10.2 kg) were randomly assigned to a physical-training group (PG; N.=20), physical and mental training group (PMG: N.=18, mental-training package [MTP] plus physical training] or control group (CG: N.=15). Physical fitness tests: countermovement jump (CMJ), medicine ball throw (MBT), bench press, and half-squat tests; hormones: resting cortisol (C) blood sample, plasma testosterone (T) concentration, and T/C ratio; and physiological variables: resting heart rate (HR), and blood pressure (BP) were assessed before training commenced (baseline) and at week 6 and 12 of training. RESULTS: PMG and PG improved performance in CMJ height (16.2%, 8.4%), MBT (27.9%, 14.2%), bench press (26.5%, 15.7%), half-squat (27.2%, 16.3%), T concentration (35.2%, 22.4%), and T/C ratio (60%, 0%, for PMG only), respectively. In contrast, the C concentration decreased for the PMG (16.3%) and increased for the PG (22%) after 12 weeks. The PMG and PG had significant decrease from pre- to post-training for the resting HR (9.1%, 3%, respectively) and BP (8.5%, 5.3%, respectively). Furthermore, there was a significant increase in MBT (9.3%) after 6 weeks in PMG. Outlined improvements (PMG and PG) were favorable compared to CG (P<0.05) in all instances. CONCLUSIONS: The greater muscular force generation in PMG than PG seem to be explained by the reduction of hormonal and physiological stress after 12 weeks. PMID- 27377253 TI - Effects of manual resistance training and free weight resistance training on postexercise blood pressure in hypertensive men: a pilot study. AB - BACKGROUND: Manual resistance training (MRT) is a low cost and practically applicable alternative form of resistance training that is ideal for weight rooms with limited equipment. The aim of this study was to compare the acute and subacute hemodynamic responses between MRT and free weight resistance training (FWRT) in normotensive (NT) and hypertensive (HT) men. METHODS: Twenty-six untrained men performed a single bout of MRT and FWRT with a minimum 72-hour rest in between. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) were measured, and double product (DP) was calculated. Variables were assessed at different time points: SBP, DBP and MBP (pre- and 15, 30, 45 and 60 minutes postexercise); DP (half-time and postintervention). RESULTS: The blood pressure values (BP) were greater in HT men in all analyses and interventions. BP responses were similar between MRT and FWRT in both groups of men. In HT men, there was postexercise hypotension (PEH) after 15, 30 and 60 minutes in MBP measured for both interventions. The DP was greater for the MRT intervention, but within the cardiovascular safety limits. CONCLUSIONS: MRT induces PEH in similar levels to FWRT in HT men. Therefore, MRT is a viable and safe alternative for application of FWRT in NT and HT men, reducing the need for expensive equipment. PMID- 27377254 TI - Upcoming Paralympic summer games in Rio: what did the German medical team learn from the London Games? AB - BACKGROUND: Musculoskeletal complaints are frequently diagnosed in Paralympic athletes. Despite the increased professionalism in Paralympic Sports, the documentation of injuries and other health complaints during high-level competition is sparse. With respect to the upcoming Paralympic Summer Games in Rio de Janeiro, the aim of this study was the analysis of all musculoskeletal complaints within the German Paralympic Athletes during the London 2012 Paralympic Games. METHODS: All musculoskeletal complaints (MSC) of the 150 German athletes seeking medical attention, hereby defined as "injury", were recorded during the in-competition period of the London Paralympics Games (22 days), regardless of their severity and consequences. Standardized documentation included the onset of symptoms, the medical diagnoses, the therapeutic measures taken as well as consecutive restrictions in training and competition. Incidence rates and localizations were analyzed by sports discipline. RESULTS: A total of 201 musculoskeletal complaints were recorded for 140 athletes (93.3%), corresponding to 1.4 musculoskeletal complaints per "injured" athlete. The incidence of musculoskeletal complaints in German athletes was 62.9+/-15.4/1000 athlete-days. High incidence rates (IR) were observed in wheelchair basketball (IR 72/1000 athlete-days, 1.6 injuries per athlete) and equestrian events (IR 72.7, 1.6). Musculoskeletal complaints were mainly located in the upper extremities (37.6%) and the spine (37.6%). The most frequent diagnoses were myalgia (N.=105, 52%). CONCLUSIONS: We noted a high rate of musculoskeletal complaints among German Paralympic athletes across sports and body parts, highlighting the need for prevention programs that focus on the upper extremities and spine. PMID- 27377255 TI - Aerobic power and field test results of amateur 15-a-side rugby union players. AB - BACKGROUND: The aim of the present study was to verify whether it is possible to predict aerobic power in amateur 15-a-side rugby union players through the Yo-Yo Intermittent Recovery Test Level 1 (Yo-Yo IRT1) and the 5-meter Multiple Shuttle Test (5-m MST). METHODS: Forty-two amateur players - 22 forwards and 20 backs - were evaluated in three phases: 1) maximum treadmill test in the laboratory; 2) field test set by a drawing in the first phase; and 3) second field test. Descriptive, comparison, correlation, regression and level of agreement analyses were performed. RESULTS: Backs, when compared to forwards, showed a higher VO2max (61.7+/-15 mL/kg/min and 51.6+/-10.1 mL/kg/min, respectively), Yo-Yo IRT1 final level (16.4+/-0.8 and 14.9+/-0.9, respectively) and Yo-Yo IRT1 total distance (1283.3+/-312.5 m and 792+/-277.6 m, respectively), and a higher final distance in the 5-m MST (686.8+/-36.6 and 642.9+/-46.5, respectively). Significant correlations were found between the result and the total distance on the Yo-Yo IRT1 and the VO2max (r=0.425 and r=0.459, respectively). Using the total distance covered in the Yo-Yo IRT1, the VO2max of amateur 15-a-side rugby union players can be estimated through the equation VO2max = 0.016 * (DIST Yo-Yo) + 40.578. CONCLUSIONS: Yo-Yo IRT1 is most useful when the objective is to evaluate the aerobic power of amateur RU players in comparison with the 5-m MST. PMID- 27377256 TI - Feasibility of higher intensity exercise in patients with chronic kidney disease. AB - BACKGROUND: Higher intensity exercise is a more effective way of evoking improvements in cardiorespiratory fitness in many chronic disease populations compared to moderate intensity continuous training. The aim of this study was to investigate the feasibility of participation in higher intensity exercise in patients with chronic kidney disease (CKD). METHODS: This study is an observational sub-study of the intervention arm of a randomized control trial. Forty-four participants with stage 3-4 CKD in the intervention arm were required to complete a predominantly home-based 12 month individualized exercise intervention. Physical activity levels, exercise capacity (METs) and blood biochemistry were measured at baseline and 12 months. The physical activity groups (higher intensity, moderate intensity and not meeting guidelines) were determined from the six months activity prior to the 12 month testing visit. RESULTS: At 12 months, the number of patients who reported performing weekly higher intensity exercise in the previous six months of the intervention increased by 23%. Participants completing higher intensity exercise had a significantly greater exercise capacity at 12 months (11.9+/-3.7 METs) than participants reporting moderate intensity exercise and those not meeting guidelines (9.2+/-1.7, 7.6+/-3.2 METs). Hemoglobin levels and exercise capacity were significantly higher at baseline in patients who reported exercising at higher intensities (142.9+/-16.1 g/L and 9.8+/-4.2 METs) compared to those reporting moderate intensity exercise (129.8+/-12.9 g/L and 8+/-3.1 METs) and not meeting guidelines (127.3+/-12.5 g/L and 6+/-2 METs). CONCLUSIONS: The study was successful in increasing higher intensity physical activity in a large proportion of patients with CKD. PMID- 27377257 TI - Effects of beta-alanine supplementation on performance and muscle fatigue in athletes and non-athletes of different sports: a systematic review. AB - INTRODUCTION: Beta-alanine (BA) is a non-essential amino acid that can be synthesized in the liver and obtained from diet, particularly from white and red meat. Increased availability of BA via dietary supplement, may improve performance of athletes. The aim of this study was to conduct a review of the use of BA supplementation as an ergogenic aid to improve performance and fatigue resistance in athletes and non-athletes. EVIDENCE ACQUISITION: In this systematic review, a search in PubMed and Bireme databases was performed for the terms "beta alanine," "beta-alanine and exercise," "carnosine" or "carnosine and exercise" in the titles or abstracts. We included randomized, clinical trials published between 2005 and 2015. EVIDENCE SYNTHESIS: Twenty-three studies were selected. Most of them included physically active individuals. The mean intervention period was 5.2+/-1.8 weeks, and mean BA dose was 4.8+/-1.3 g/day. The main outcome measures were blood lactate, pH, perceived exertion, power and physical working capacity at fatigue threshold. After BA supplementation, no statistically significant difference was observed in total work, exercise performance time, oxygen consumption and time to exhaustion. CONCLUSIONS: BA supplementation seems to improve perceived exertion and biochemical parameters related to muscle fatigue and less evidence was found for improvement in performance. PMID- 27377258 TI - Proteomic characterization of platelet gel releasate from adult peripheral and cord blood. AB - PURPOSE: Activated platelet gel (PG) derived from adult peripheral blood (APB) has been extensively used for topical therapy of various clinical conditions. Conversely, few observations on PG from umbilical cord blood (CB) have been reported so far. Although PG preparations are known to contain a high concentration of a large number of biological factors involved in inflammation and tissue repair, their comprehensive characterization is still missing. The innovative goal of our research was to use proteomics technologies in order to profile biologically active components in these blood derivatives. EXPERIMENTAL DESIGN: Supernatants recovered from three independent APB and CB-derived PGs, prepared using batroxobin, were enriched for low-abundance proteins with ProteoMiner and subsequently analyzed by GeLC-MS/MS. RESULTS: The 751 and 760 proteins were identified in the APB and CB-derived PG releasates, respectively. A core dataset including only proteins found in 2/3 and 3/3 biological replicates was generated and functionally characterized by gene ontology. Searching against Vesiclepedia database showed that 33% of our dataset consists of novel releasate proteins. Comparison between the two types of PG secretomes revealed that 117 proteins are present only in the APB-derived samples, 104 proteins are distinctive of the CB-derived samples, and 229 are in common. CONCLUSION AND CLINICAL RELEVANCE: Our study highlighted a differential content of proteins supporting tissue repair and regeneration between APB and CB-derived PGs. These findings may help better identifying future appropriate clinical applications. PMID- 27377259 TI - The kinetics and mechanism of the organo-iridium catalysed racemisation of amines. AB - The dimeric iodo-iridium complex [IrCp*I2]2 (Cp* = pentamethylcyclopentadiene) is an efficient catalyst for the racemisation of secondary and tertiary amines at ambient and higher temperatures with a low catalyst loading. The racemisation occurs with pseudo-first-order kinetics and the corresponding four rate constants were obtained by monitoring the time dependence of the concentrations of the (R) and (S) enantiomers starting with either pure (R) or (S) and show a first-order dependence on catalyst concentration. Low temperature (1)H NMR data is consistent with the formation of a 1 : 1 complex with the amine coordinated to the iridium and with both iodide anions still bound to the metal-ion, but at the higher temperatures used for kinetic studies binding is weak and so no saturation zero order kinetics are observed. A cross-over experiment with isotopically labelled amines demonstrates the intermediate formation of an imine which can dissociate from the iridium complex. Replacing the iodides in the catalyst by other ligands or having an amide substituent in Cp* results in a much less effective catalysts for the racemisation of amines. The rate constants for a deuterated amine yield a significant primary kinetic isotope effect kH/kD = 3.24 indicating that hydride transfer is involved in the rate-limiting step. PMID- 27377260 TI - Noria: A Highly Xe-Selective Nanoporous Organic Solid. AB - Separation of xenon and krypton is of industrial and environmental concern; the existing technologies use cryogenic distillation. Thus, a cost-effective, alternative technology for the separation of Xe and Kr and their capture from air is of significant importance. Herein, we report the selective Xe uptake in a crystalline porous organic oligomeric molecule, noria, and its structural analogue, PgC-noria, under ambient conditions. The selectivity of noria towards Xe arises from its tailored pore size and small cavities, which allows a directed non-bonding interaction of Xe atoms with a large number of carbon atoms of the noria molecular wheel in a confined space. PMID- 27377261 TI - Radiosurgery with flattening-filter-free techniques in the treatment of brain metastases : Plan comparison and early clinical evaluation. AB - BACKGROUND: Radiosurgical treatment of brain metastases is well established in daily clinical routine. Utilization of flattening-filter-free beams (FFF) may allow for more rapid delivery of treatment doses and improve clinical comfort. Hence, we compared plan quality and efficiency of radiosurgery in FFF mode to FF techniques. MATERIALS AND METHODS: Between November 2014 and June 2015, 21 consecutive patients with 25 brain metastases were treated with stereotactic radiosurgery (SRS) in FFF mode. Brain metastases received dose-fractionation schedules of 1 * 20 Gy or 1 * 18 Gy, delivered to the conformally enclosing 80 % isodose. Three patients with critically localized or large (>3 cm) brain metastases were treated with 6 * 5 Gy. Plan quality and efficiency were evaluated by analyzing conformity, dose gradients, dose to healthy brain tissue, treatment delivery time, and number of monitor units. FFF plans were compared to those using the FF method, and early clinical outcome and toxicity were assessed. RESULTS: FFF mode resulted in significant reductions in beam-on time (p < 0.001) and mean brain dose (p = 0.001) relative to FF-mode comparison plans. Furthermore, significant improvements in dose gradients and sharper dose falloffs were found for SRS in FFF mode (-1.1 %, -29.6 %; p <= 0.003), but conformity was slightly superior in SRS in FF mode (-1.3 %; p = 0.001). With a median follow-up time of 5.1 months, 6-month overall survival was 63.3 %. Local control was observed in 24 of 25 brain metastases (96 %). CONCLUSION: SRS in FFF mode is time efficient and provides similar plan quality with the opportunity of slightly reduced dose exposure to healthy brain tissue when compared to SRS in FF mode. Clinical outcomes appear promising and show only modest treatment-related toxicity. PMID- 27377262 TI - Transient Grating Spectroscopy in Magnetic Thin Films: Simultaneous Detection of Elastic and Magnetic Dynamics. AB - Surface magnetoelastic waves are coupled elastic and magnetic excitations that propagate along the surface of a magnetic material. Ultrafast optical techniques allow for a non-contact excitation and detection scheme while providing the ability to measure both elastic and magnetic components individually. Here we describe a simple setup suitable for excitation and time resolved measurements of high frequency magnetoelastic waves, which is based on the transient grating technique. The elastic dynamics are measured by diffracting a probe laser pulse from the long-wavelength spatially periodic structural deformation. Simultaneously, a magnetooptical measurement, either Faraday or Kerr effect, is sensitive to the out-of-plane magnetization component. The correspondence in the response of the two channels probes the resonant interaction between the two degrees of freedom and reveals their intimate coupling. Unraveling the observed dynamics requires a detailed understanding of the spatio-temporal evolution of temperature, magnetization and thermo-elastic strain in the ferromagnet. Numerical solution of thermal diffusion in two dimensions provides the basis on which to understand the sensitivity in the magnetooptic detection. PMID- 27377263 TI - Conductive Polymer-Coated VS4 Submicrospheres As Advanced Electrode Materials in Lithium-Ion Batteries. AB - VS4 as an electrode material in lithium-ion batteries holds intriguing features like high content of sulfur and one-dimensional structure, inspiring the exploration in this field. Herein, VS4 submicrospheres have been synthesized via a simple solvothermal reaction. However, they quickly degrade upon cycling as an anode material in lithium-ion batteries. So, three conductive polymers, polythiophene (PEDOT), polypyrrole (PPY), and polyaniline (PANI), are coated on the surface to improve the electron conductivity, suppress the diffusion of polysulfides, and modify the interface between electrode/electrolyte. PANI is the best in the polymers. It improves the Coulombic efficiency to 86% for the first cycle and keeps the specific capacity at 755 mAh g(-1) after 50 cycles, higher than the cases of naked VS4 (100 mAh g(-1)), VS4@PEDOT (318 mAh g(-1)), and VS4@PPY (448 mAh g(-1)). The good performances could be attributed to the improved charge-transfer kinetics and the strong interaction between PANI and VS4 supported by theoretical simulation. The discharge voltage ~2.0 V makes them promising cathode materials. PMID- 27377265 TI - Erratum to: Detection of chikungunya virus in saliva and urine. PMID- 27377264 TI - Occurrence of canine parvovirus in dogs from Henan province of China in 2009 2014. AB - BACKGROUND: There is no information concerning the genotype of Canine parvovirus (CPV) currently circulating in Henan province, China. Therefore, the aim of the present study was to provide insights into the epidemiology and molecular characterization of CPV circulating in Henan province from 2009 to 2014. RESULTS: Nineteen thousand nine hundred seven dogs from pet hospitals in the cities of Luoyang, Anyang, Jiaozuo, Sanmenxia, Xinxiang, Zhengzhou in Henan province between 2009 and 2014 were investigated. Over the 6-year period, 1169 CPV positive cases were identified and the morbidity of CPV infection ranged from 4.16 to 8.06 %, although morbidity was not significant (P > 0.05) between 2009 and 2014. Factors associated with morbidity included sampling season, dog age, breed, vaccination status, and sex. CPV co-infection with coccidium (10.00 %), canine distemper virus (4.79 %), hookworm (2.40 %), canine coronavirus (1.11 %), roundworm (1.03 %), tapeworm (0.17 %) and Babesia spp. (0.09 %) were observed. The new CPV-2a variant was more prevalent than the new CPV-2b variant in Henan province. CPV 2c was not observed in this study. CONCLUSIONS: The epidemiology of CPV infection and identification of the circulating genotypes in Henan province, China from 2009 to 2014 determined that the new CPV-2a variant was more prevalent. PMID- 27377267 TI - Erratum to: Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses vasculogenic mimicry and proliferation of highly aggressive pancreatic cancer PaTu8988 cells. PMID- 27377266 TI - Evaluation of diagnostic performance of rK28 ELISA using urine for diagnosis of visceral leishmaniasis. AB - BACKGROUND: Recombinant fusion proteins are now commonly used to detect circulating antibodies for the serodiagnosis of visceral leishmaniasis (VL) in Asia, Africa and the Americas. Although simple, these tests still require blood collection and their use in remote settings can be limited due to the need of collection devices, serum fractionation instrument and generation of biohazardous waste. The development of an accurate and non-invasive diagnostic algorithm for VL, such as could be achieved with urine, is desirable. METHODS: We enrolled 87 VL patients and 81 non-VL individuals, including 33 healthy endemic controls, 16 healthy non-endemic controls, 16 disease controls and 16 tuberculosis (TB) patients. We compared the efficacy of recombinant antigens rK28, rK39 and rKRP42 for the diagnosis of VL when either serum or urine were used to develop antibody detection ELISA. RESULTS: As expected, each of the antigens readily detected antibodies in the serum of VL patients. rK28 ELISA showed the highest sensitivity (98.9 %), followed by rK39 and rKRP42 ELISA (97.7 and 94.4 %, respectively); overall specificity was > 96 %. When urine was used as the test analyte, only a marginal drop in sensitivity was observed, with rK28 ELISA again demonstrating the greatest sensitivity (95.4 %), followed by rK39 and rKRP42 ELISA, respectively. Again, the overall specificity was > 96 %. CONCLUSIONS: Our data indicate the potential for using urine in the diagnosis of VL. Detection of antibodies against rK28 demonstrated the greatest sensitivity. Together, our results indicate that rK28-based antibody detection tests using urine could provide a completely non-invasive tool amenable for diagnosis of VL in remote locations. PMID- 27377269 TI - A Pd4Br4 macrocycle trapped by cocrystallization from a highly dynamic equilibrium of eta(3)-cycloheptatrienide complexes. AB - In the coordination chemistry of palladium, dimers bridged via halides are a common motif. Higher oligomers, however, are still rare. We report the structure of an alternating eight-membered [Pd4Br4](4-) ring framed by cycloheptatrienide ligands, which was obtained by cocrystallization of dimers and tetramers of the complex salt bromido{eta(3)-[3-(2,6-diisopropylphenyl)imidazolium-1 yl]cycloheptatrienido}palladium(II) tetrafluoroborate, namely bis[di-MU-bromido bis({eta(3)-[3-(2,6-diisopropylphenyl)imidazolium-1 yl]cycloheptatrienido}palladium(II))] cyclo-tetra-MU-bromido-tetrakis({eta(3)-[3 (2,6-diisopropylphenyl)imidazolium-1-yl]cycloheptatrienido}palladium(II)) octakis(tetrafluoroborate) dichloromethane octasolvate, [Pd4Br4(C22H26N2)4][Pd2Br2(C22H26N2)2]2(BF4)8.8CH2Cl2. These dimers and tetramers form a highly dynamic equilibrium in solution which was studied by low temperature NMR spectroscopy. In the light of the presented results, tetrameric Pd(II) species can be assumed to co-exist as a second species in many cases where by current knowledge only a dimeric compound would be expected. PMID- 27377270 TI - Diminished electron density in the Vaska-type rhodium(I) complex trans [Rh(NCBH3)(CO)(PPh3)2]. AB - Vaska-type complexes, i.e. trans-[RhX(CO)(PPh3)2] (X is a halogen or pseudohalogen), undergo a range of reactions and exhibit considerable catalytic activity. The electron density on the Rh(I) atom in these complexes plays an important role in their reactivity. Many cyanotrihydridoborate (BH3CN(-)) complexes of Group 6-8 transition metals have been synthesized and structurally characterized, an exception being the rhodium(I) complex. Carbonyl(cyanotrihydridoborato-kappaN)bis(triphenylphosphine-kappaP)rhodium(I), [Rh(NCBH3)(CO)(C18H15P)2], was prepared by the metathesis reaction of sodium cyanotrihydridoborate with trans-[RhCl(CO)(PPh3)2], and was characterized by single-crystal X-ray diffraction analysis and IR, (1)H, (13)C and (11)B NMR spectroscopy. The X-ray diffraction data indicate that the cyanotrihydridoborate ligand coordinates to the Rh(I) atom through the N atom in a trans position with respect to the carbonyl ligand; this was also confirmed by the IR and NMR data. The carbonyl stretching frequency nu(CO) and the carbonyl carbon (1)JC-Rh and (1)JC-P coupling constants of the Cipso atoms of the triphenylphosphine groups reflect the diminished electron density on the central Rh(I) atom compared to the parent trans-[RhCl(CO)(PPh3)2] complex. PMID- 27377268 TI - Suppression of cell migration is promoted by miR-944 through targeting of SIAH1 and PTP4A1 in breast cancer cells. AB - BACKGROUND: Aberrant expression of microRNAs has been associated with migration of tumor cells. In this study, we aimed to investigate the biological significance of miR-944 whose function is unknown in breast cancer. METHODS: MiR 944 expression in breast cancer cells and tumors was evaluated by Taqman qRT-PCR assays. Transcriptional profiling of MDA-MB-231 cells expressing miR-944 was performed using DNA microarrays. Cell viability, migration and invasion were assessed by MTT, scratch/wound-healing and transwell chamber assays, respectively. The luciferase reporter assay was used to evaluate targeting of SIAH1, PTP4A1 and PRKCA genes by miR-944. SIAH1 protein levels were measured by Western blot. Silencing of SIAH1 gene was performed by RNA interference using shRNAs. RESULTS: Our data showed that miR-944 expression was severely repressed in clinical specimens and breast cancer cell lines. Suppression of miR-944 levels was independent of hormonal status and metastatic potential of breast cancer cells. Gain-of-function analysis indicated that miR-944 altered the actin cytoskeleton dynamics and impaired cell migration and invasion. Genome-wide transcriptional profiling of MDA-MB-231 cells that ectopically express miR-944 showed that 15 genes involved in migration were significantly repressed. Notably, luciferase reporter assays confirmed the ability of miR-944 to bind the 3'UTR of SIAH1 and PTP4A1 genes, but not PRKCA gene. Congruently, an inverse correlation between miR-944 and SIAH1 protein expression was found in breast cancer cells. Moreover, SIAH1 was upregulated in 75 % of miR-944-deficient breast tumors. Finally, SIAH1 gene silencing by RNA interference significantly impaired cell migration of breast cancer cells. CONCLUSIONS: Our results pointed out that miR 944 is a novel upstream negative regulator of SIAH1 and PTP4A1 genes and provided for the first time evidence for its functional role in migration and invasion of breast cancer cells. They also suggest that miR-944 restoration may represent a potential strategy for breast cancer therapy. PMID- 27377271 TI - A study of the planarity of the pyrrolone fragment in 2-isopropyl-2,3-dihydro-1H isoindol-1-one. AB - Orthophthalaldehyde (o-phthalaldehyde, OPA) is an aromatic dialdehyde bearing two electron-withdrawing carbonyl groups. The reactions of OPA with primary amines are broadly applied for the synthesis of important heterocyclic compounds with biological relevance. A number of such reactions have been investigated recently and several structures of condensation products have been reported, however, the complex reaction mechanism is still not fully understood and comprises concurrent as well as consecutive reactions. The reaction products depend on the primary amine which reacts with OPA, the reaction environment (solvent) and the proportion of the reactants. The title molecule, C11H13NO, the product of the reaction of OPA with isopropylamine, contains a five-membered pyrrole C4N ring with a carbonyl substituent, which forms part of the isoindolinone unit. Though this pyrrole ring contains one C atom in the sp(3)-hybridized state, it is fairly planar. The title molecule has been compared with similar structures retrieved from the Cambridge Structural Database in order to study this phenomenon. The planarity of this fragment has been explained by the presence of partially delocalized C-C, C-N and C-O bonds, and by an inner angle in the planar pentagonal ring (~108 degrees ), which is close to the ideal tetrahedral value for the sp(3)-hybridized state of the constituent C atom. Due to this propitious angle, this C atom can be present in states intermediate between sp(3)- and sp(2) hybridized in different structures, while still maintaining the planarity of the ring. There are only weak intermolecular C-H...O hydrogen bonds and C-H...pi electron ring interactions in the structure. In particular, it is the pyrrole ring which is involved in these interactions. PMID- 27377272 TI - Intermolecular Pb...N interactions in lead(II) dimers producing a supramolecular two-dimensional metal-organic compound: bis[MU2-N'-(2 oxidobenzylidene)benzohydrazidato-kappa(4)O:O,N',O']dilead(II). AB - Aroylhydrazones of ortho-hydroxy aldehydes are Schiff base ligands that typically coordinate as a chelate in an O,N,O'-manner. Dinuclear complexes are normally observed, with the phenolate O atom acting as the bridging atom. The switchable protonation state of the tridentate N'-(2-hydroxybenzylidene)benzohydrazide (H2sabhz) ligand can lead to variations in the resulting supramolecular structure. The title compound, [Pb2(C14H10N2O2)2], was prepared by the reaction of [Pb(OAc)2].3H2O (OAc is acetate) with the benzoylhydrazone derivative of salicylaldehyde, i.e. H2sabhz, in the presence of triethylamine in methanol. In the crystal structure, each Pb(II) atom of the dimer has an NO3 coordination environment, with one sabhz ligand coordinating in an O,N,O'-manner and with the second sabhz ligand coordinating via the bridging phenolate O atom, since the dimers are located on a centre of inversion. It has been found that the dimers are connected by Pb...N interactions, resulting in a two-dimensional supramolecular network which shows the [3(2).5(2),3.5(3)] net topology. The s(2) electron pair of the Pb(II) ion clearly influences the observed intermolecular interactions. PMID- 27377273 TI - A new three-dimensional zinc(II) coordination polymer involving 2-[(1H-1,2,4 triazol-1-yl)methyl]-1H-benzimidazole and benzene-1,4-dicarboxylate ligands. AB - Metal-organic frameworks (MOFs) based on multidentate N-heterocyclic ligands involving imidazole, triazole, tetrazole, benzimidazole, benzotriazole or pyridine present intriguing molecular topologies and have potential applications in ion exchange, magnetism, gas sorption and storage, catalysis, optics and biomedicine. The 2-[(1H-1,2,4-triazol-1-yl)methyl]-1H-benzimidazole (tmb) ligand has four potential N-atom donors and can act in monodentate, chelating, bridging and tridentate coordination modes in the construction of complexes, and can also act as both a hydrogen-bond donor and acceptor. In addition, the tmb ligand can adopt different coordination conformations, resulting in complexes with helical structures due to the presence of the flexible methylene spacer. A new three dimensional coordination polymer, poly[[bis(MU2-benzene-1,4-dicarboxylato) kappa(4)O(1),O(1'):O(4),O(4');kappa(2)O(1):O(4)-bis{MU2-2-[(1H-1,2,4-triazol-1 yl)methyl-kappaN(4)]-1H-benzimidazole-kappaN(3)}dizinc(II)] trihydrate], {[Zn(C8H4O4)(C10H9N5)].1.5H2O}n, has been synthesized by the reaction of ZnCl2 with tmb and benzene-1,4-dicarboxylic acid (H2bdic) under solvothermal conditions. There are two crystallographically distinct bdic(2-) ligands [bdic(2 )(A) and bdic(2-)(B)] in the structure which adopt different coordination modes. The Zn(II) ions are bridged by tmb ligands, leading to one-dimensional helical chains with different handedness, and adjacent helices are linked by bdic(2-)(A) ligands, forming a two-dimensional network structure. The two-dimensional layers are further connected by bdic(2-)(B) ligands, resulting in a three-dimensional framework with the topological notation 6(6). The IR spectra and thermogravimetric curves are consistent with the results of the X-ray crystal structure analysis and the title polymer exhibits good fluorescence in the solid state at room temperature. PMID- 27377274 TI - A phase transition from monoclinic C2 with Z' = 1 to triclinic P1 with Z' = 4 for the quasiracemate L-2-aminobutyric acid-D-methionine (1/1). AB - Racemates of hydrophobic amino acids with linear side chains are known to undergo a unique series of solid-state phase transitions that involve sliding of molecular bilayers upon heating or cooling. Recently, this behaviour was shown to extend also to quasiracemates of two different amino acids with opposite handedness [Gorbitz & Karen (2015). J. Phys. Chem. B, 119, 4975-4984]. Previous investigations are here extended to an L-2-aminobutyric acid-D-methionine (1/1) co-crystal, C4H9NO2.C5H11NO2S. The significant difference in size between the CH2CH3 and -CH2CH2SCH3 side chains leads to extensive disorder at room temperature, which is essentially resolved after a phase transition at 229 K to an unprecedented triclinic form where all four D-methionine molecules in the asymmetric unit have different side-chain conformations and all three side-chain rotamers are used for the four partner L-2-aminobutyric acid molecules. PMID- 27377275 TI - A novel binuclear copper complex incorporating a nalidixic acid derivative displaying a one-dimensional coordination polymeric structure. AB - The identification of the antibacterial action of nalidixic acid (nx) was central to the development of the quinolone antibacterial compounds. The ability of the nx naphthyridyl ring to interact with and inhibit some proteins has encouraged the investigation of similar structures in the search for more active compounds with less adverse effects. The possibility of structural modification by attachment of other biologically active moieties to the naphthyridyl ring of nx allowed the development of new active antimicrobial molecules. Hydrazone derivatives of nx can be synthesized easily based on the condensation of the hydrazide derivative of nx with the desired aldehyde or ketone. Only a few complexes with nx hydrazone derivatives have been described but for none were the crystal structures elucidated. The synthesis of a new one-dimensional Cu(II) coordination polymer, namely catena-poly[[copper(II)-di-MU-chlorido-copper(II) {MU-1-ethyl-N'-[(1H-imidazol-4-yl)methylidene]-7-methyl-4-oxo-1,4-dihydro-1,8 naphthyridine-3-carbohydrazidato}-[dimethanolcopper(II)]-{MU-1-ethyl-N'-[(1H imidazol-3-yl)methylidene]-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3 carbohydrazidato}] dichloride methanol tetrasolvate], {[Cu3(C16H15N6O2)2Cl2(CH3OH)2]Cl2.4CH3OH}n, with the (1H-imidazol-4 yl)methylidene carbohydrazide derivative of nalidixic acid (denoted h4imi), is presented and its structure is compared to the density functional theory (DFT) optimized structure of free h4imi. The title structure presents an octahedral Cu(II) ion on an inversion centre alternating along a polymer chain with a square pyramidal Cu(II) ion, with the two Cu(II) centres bridged by two chloride ligands. Hydrogen bonds involving chloride counter-ions and methanol solvent molecules mediate the three-dimensional packing of the polymer. Comparison of the geometrical results from the structure analysis with those derived from a DFT study of the free ligand reveal the differences that arise upon coordination. PMID- 27377276 TI - Diastereoisomeric forms of 11-ethyl-6,11-dihydro-5H-dibenzo[b,e]azepine-6 carboxamide: syntheses and the molecular and supramolecular structure of the minor form (6RS,11RS)-11-ethyl-6,11-dihydro-5H-dibenzo[b,e]azepine-6-carboxamide. AB - Compounds containing the tricyclic dibenzo[b,e]azepine system have potential activity in the treatment of a number of diseases. Continuing with our studies on the synthesis of new small and potentially bioactive molecules, a synthetic route, involving acid-catalysed intramolecular Friedel-Crafts cyclization, to the readily separable diastereoisomers of 11-ethyl-6,11-dihydro-5H dibenzo[b,e]azepine-6-carboxamide, a potentially useful precursor in the synthesis of analogues of some anti-allergenic, antidepressant and antihistaminic drugs currently in use, has been developed starting from 2-allylphenylamine and methyl 2-bromo-2-phenylacetate and proceeding via racemic methyl 2-[(2 allylphenyl)amino]-2-phenylacetate (A) and racemic 2-[(2-allylphenyl)amino]-2 phenylacetamide (B), to give the two diastereoisomers (I) and (II), C17H18N2O. Isomers (I) and (II), and their precursors (A) and (B), have all been fully characterized spectroscopically. Structure analysis of the minor isomer (I) shows that it has the (6RS,11RS) configuration, and that the azepine ring adopts a conformation intermediate between the boat and twist-boat forms, with the carboxamide and ethyl substituents both occupying quasi-equatorial sites. The molecules of (I) are linked by a combination of N-H...O, N-H...pi(arene) and C H...pi(arene) hydrogen bonds to form complex sheets. Comparisons are made with the structures of some related compounds. PMID- 27377277 TI - A cyanide-bridged heterometallic coordination polymer constructed from square planar [Ni(CN)4](2-): synthesis, crystal structure, thermal decomposition, electron paramagnetic resonance (EPR) spectrum and magnetic properties. AB - Square-planar complexes are commonly formed by transition metal ions having a d(8) electron configuration. Planar cyanometallate anions have been used extensively as design elements in supramolecular coordination systems. In particular, square-planar tetracyanometallate(II) ions, i.e. [M(CN)4](2-) (M(II) = Ni, Pd or Pt), are used as good building blocks for bimetallic Hofmann-type assemblies and their analogues. Square-planar tetracyanonickellate(II) complexes have been extensively developed with N-donor groups as additional co-ligands, but studies of these systems using O-donor ligands are scarce. A new cyanide-bridged Cu(II)-Ni(II) heterometallic compound, poly[[diaquatetra-MU2-cyanido-kappa(8)C:N nickel(II)copper(II)] monohydrate], {[Cu(II)Ni(II)(CN)4(H2O)2].H2O}n, has been synthesized and characterized by X-ray single-crystal diffraction analyses, vibrational spectroscopy (FT-IR), thermal analysis, electron paramagnetic resonance (EPR) and magnetic moment measurements. The structural analysis revealed that it has a two-dimensional grid-like structure built up of cationic [Cu(H2O)2](2+) and anionic [Ni(CN)4](2-) units connected through bridging cyanide ligands. The overall three-dimensional supramolecular network is expanded by a combination of interlayer O-H...N and intralayer O-H...O hydrogen-bond interactions. The first decomposition reactions take place at 335 K under a static air atmosphere, which illustrates the existence of guest water molecules in the interlayer spaces. The electron paramagnetic resonance (EPR) spectrum confirms that the Cu(II) cation has an axial coordination symmetry and that the unpaired electrons occupy the d(x(2)-y(2)) orbital. In addition, magnetic investigations showed that antiferromagnetic interactions exist in the Cu(II) atoms through the diamagnetic [Ni(CN)4](2-) ion. PMID- 27377278 TI - Li4Ge2B as a new derivative of the Mo2B5 and Li5Sn2 structure types. AB - Binary and multicomponent intermetallic compounds based on lithium and p-elements of Groups III-V of the Periodic Table are useful as modern electrode materials in lithium-ion batteries. However, the interactions between the components in the Li Ge-B ternary system have not been reported. The structure of tetralithium digermanium boride, Li4Ge2B, exhibits a new structure type, in the noncentrosymmetric space group R3m, in which all the Li, Ge and B atoms occupy sites with 3m symmetry. The title structure is closely related to the Mo2B5 and Li5Sn2 structure types, which crystallize in the centrosymmetric space group R 3m. All the atoms in the title structure are coordinated by rhombic dodecahedra (coordination number = 14), similar to the atoms in related structures. According to electronic structure calculations using the tight-binding-linear muffin-tin orbital-atomic spheres approximation (TB-LMTO-ASA) method, strong covalent Ge-Ge and Ge-B interactions were established. PMID- 27377279 TI - Conformational dimorphism in o-nitrobenzoic acid: alternative ways to avoid the O...O clash. AB - Polymorphism is a challenging phenomenon and the competitive packing alternatives which are characteristic for polymorphs may be encountered for essentially rigid molecules. A second crystal form of the well known compound o-nitrobenzoic acid, C7H5NO4, an important intermediate in the production of dyes, pharmaceuticals and agrochemicals, is described. Although obtained serendipitously, its intra- and intermolecular features match expectations from database searches and theoretical calculations. O-H...O hydrogen-bonded carboxylic acid dimers represent the building blocks in both polymorphs. For steric reasons and in agreement with a calculated potential energy surface, the carboxylic acid and nitro groups cannot simultaneously be coplanar with the benzene ring but have to tilt. In the well established crystal form, this out-of-plane torsion is more pronounced for the nitro substituent. In contrast, the new polymorph is characterized by a major tilt of the carboxylic acid group. The molecules in both alternative crystal forms achieve a similar compromise with respect to acceptable intramolecular O...O contacts. PMID- 27377280 TI - A polymeric silver thiosaccarinate complex with a two-dimensional triply entangled mesh and argentophilic interactions. AB - Silver(I) complexes with sulfur-donor ligands have a broad range of pharmacological applications. One of the most important factors for tuning the biological activity is the type of donor atom and the ease of ligand replacement. Silver thiosaccharinates display a wide range of structures from mono- to polynuclear complexes. We report the synthesis, crystal structure and vibrational spectroscopic analysis of a two-dimensional Ag(I)-thiosaccharinate coordination polymer, namely poly[tris(MU2-4,4'-bipyridine-kappa(2)N:N')bis(MU3-1,1-dioxo-1,2 benzisothiazole-3-thiolato-kappa(3)N:S(3):S(3))bis(MU2-1,1-dioxo-1,2 benzisothiazole-3-thiolato-kappa(2)S(3):S(3))tetrasilver(I)], [Ag2(C7H4NO2S2)2(C10H8N2)1.5]n, with 4,4'-bipyridine acting as a spacer. A relevant feature of the structure is the presence of an unusually short Ag...Ag separation of 2.8859 (10) A, well within the range of argentophilic interactions and confirmed as such by Raman analysis of the low-frequency spectrum. From a topological point of view, the structure presents interpenetration in the form of a threefold entangled 2D->2D mesh (2D is two-dimensional). PMID- 27377281 TI - Di- and triphenylacetate complexes of yttrium and europium. AB - The significant variety in the crystal structures of rare-earth carboxylate complexes is due to both the large coordination numbers of the rare-earth cations and the ability of the carboxylate anions to form several types of bridges between rare-earth metal atoms. Therefore, these complexes are represented by mono-, di- and polynuclear complexes, and by coordination polymers. The interaction of LnCl3(thf)x (Ln = Eu or Y; thf is tetrahydrofuran) with sodium or diethylammonium diphenylacetate in methanol followed by recrystallization from a DME/THF/hexane solvent mixture (DME is 1,2-dimethoxyethane) leads to crystals of the non-isomorphic dinuclear complexes tetrakis(MU-2,2-diphenylacetato) kappa(4)O:O';kappa(3)O,O':O';kappa(3)O:O,O'-bis[(1,2-dimethoxyethane kappa(2)O,O')(2,2-diphenylacetato-kappa(2)O,O')europium(III)], [Eu(C14H11O2)6(C4H10O2)2], (I), and tetrakis(MU-2,2-diphenylacetato) kappa(4)O:O';kappa(3)O,O':O';kappa(3)O:O,O'-bis[(1,2-dimethoxyethane kappa(2)O,O')(2,2-diphenylacetato-kappa(2)O,O')yttrium(III)], [Y(C14H11O2)6(C4H10O2)2], (II), possessing monoclinic (P21/c) symmetry. The [Ln(Ph2CHCOO)3(dme)]2 molecule (Ln = Eu or Y) lies on an inversion centre and exhibits three different coordination modes of the diphenylacetate ligands, namely bidentate kappa(2)O,O'-terminal, bidentate MU2-kappa(1)O:kappa(1)O' bridging and tridentate MU2-kappa(1)O:kappa(2)O,O'-semibridging. The terminal and bridging ligands in (I) are disordered over two positions, with an occupancy ratio of 0.806 (2):0.194 (2). The interaction of EuCl3(thf)2 with Na[Ph3CCOO] in methanol followed by crystallization from hot methanol produces crystals of tetrakis(methanol-kappaO)tris(2,2,2-triphenylacetato)-kappa(4)O:O';kappaO europium(III) methanol disolvate, [Eu(C19H15O2)3(CH3OH)4].2CH3OH, (III).2MeOH, with triclinic (P-1) symmetry. The molecule of (III) contains two O,O'-bidentate and one O-monodentate terminal triphenylacetate ligand. (III).2MeOH possesses one intramolecular and four intermolecular hydrogen bonds, forming a [(III).2MeOH]2 dimer with two bridging methanol molecules. PMID- 27377282 TI - X-ray characterization and magnetic properties of dioxygen-bridged Cu(II) and Mn(III) Schiff base complexes. AB - The coordination chemistry of multinuclear metal compounds is important because of their relevance to the multi-metal active sites of various metalloproteins and metalloenzymes. Multinuclear Cu(II) and Mn(III) compounds are of interest due to their various properties in the fields of coordination chemistry, inorganic biochemistry, catalysis, and optical and magnetic materials. Oxygen-bridged binuclear Mn(III) complexes generally exhibit antiferromagnetic interactions and a few examples of ferromagnetic interactions have also been reported. Binuclear Cu(II) complexes are important due to the fact that they provide examples of the simplest case of magnetic interaction involving only two unpaired electrons. Two novel dioxygen-bridged copper(II) and manganese(III) Schiff base complexes, namely bis(MU-4-bromo-2-{[(3-oxidopropyl)imino]methyl}phenolato)dicopper(II), [Cu2(C10H10BrNO2)2], (1), and bis(diaqua{4,4'-dichloro-2,2'-[(1,1-dimethylethane 1,2-diyl)bis(nitrilomethanylylidene)]diphenolato}manganese(III)) bis{MU-4,4' dichloro-2,2'-[(1,1-dimethylethane-1,2 diyl)bis(nitrilomethanylylidene)]diphenolato}bis[aquamanganese(III)] tetrakis(perchlorate) ethanol disolvate, [Mn(C18H16Cl2N2O2)(H2O)2]2[Mn2(C18H16Cl2N2O2)2(H2O)2](ClO4)4.2C2H5OH, (2), have been synthesized and single-crystal X-ray diffraction has been used to analyze their crystal structures. The structure analyses of (1) and (2) show that each Cu(II) atom is four-coordinated, with long weak Cu...O interactions of 2.8631 (13) A linking the dinuclear halves of the centrosymmetric tetranucelar molecules, while each Mn(III) atom is six-coordinated. The shortest intra- and intermolecular nonbonding Mn...Mn separations are 3.3277 (16) and 5.1763 (19) A for (2), while the Cu...Cu separations are 3.0237 (3) and 3.4846 (3) A for (1). The magnetic susceptibilities of (1) and (2) in the solid state were measured in the temperature range 2-300 K and reveal the presence of antiferromagnetic spin exchange interactions between the transition metal ions. PMID- 27377283 TI - Monitoring photo-induced transformations in crystals of 2,6-difluorocinnamic acid under ambient conditions. AB - Several conditions need to be fulfilled for a photochemical reaction to proceed in crystals. Some of these conditions, for example, geometrical conditions, depend on the particular type of photochemical reaction, but the rest are common for all reactions. The mutual directionality of two neighbouring molecules determines the kind of product obtained. The influence of temperature on the probability of a photochemical reaction occurring varies for different types of photochemical reaction and different compounds. High pressure imposed on crystals also has a big influence on the free space and the reaction cavity. The wavelength of the applied UV light is another factor which can initiate a reaction and sometimes determine the structure of a product. It is possible, to a certain degree, to control the packing of molecules in stacks by using fluoro substituents on benzene rings. The crystal and molecular structure of 2,6 difluorocinnamic acid [systematic name: 3-(2,6-difluorophenyl)prop-2-enoic acid], C9H6F2O2, (I), was determined and analysed in terms of a photochemical [2 + 2] dimerization. The molecules are arranged in stacks along the a axis and the values of the intermolecular geometrical parameters indicate that they may undergo this photochemical reaction. The reaction was carried out in situ and the changes of the unit-cell parameters during crystal irradiation by a UV beam were monitored. The values of the unit-cell parameters change in a different manner, viz. cell length a after an initial increase starts to decrease, b after a decrease starts to increase, c increases and the unit-cell volume V after a certain increase starts to decrease. The structure of a partially reacted crystal, i.e. containing both the reactant and the product, namely 2,6 difluorocinnamic acid-3,4-bis(2,6-difluorophenyl)cyclobutane-1,2-dicarboxylic acid (0.858/0.071), 0.858C9H6F2O2.0.071C18H12F4O4, obtained in situ, is also presented. The powder of compound (I) was irradiated with UV light and afterwards crystallized [as 3,4-bis(2,6-difluorophenyl)cyclobutane-1,2-dicarboxylic acid toluene hemisolvate, C18H12F4O4.0.5C7H8] in a space group different from that of the crystal containing the in-situ dimer. PMID- 27377285 TI - Genetic risk factors for venous thrombosis in the elderly in a case-control study. AB - Essentials Risk of venous thrombosis (VT) related to common genetic variants in those aged 70+ is unknown. We studied Factor V Leiden, prothrombin mutation, non O blood group and family history (FH) of VT. Risk of VT was increased 2.2-, 1.4-, 1.3- and 2.1-fold respectively. FH is easy to obtain and can be implemented in clinical decision rules of VT risk in the elderly. Click to hear Prof. Reitsma discuss genetic risk factors of arterial and venous thrombosis SUMMARY: Background As the incidence of venous thrombosis (VT) increases steeply with age and the number of elderly people is on the rise, studies of VT in this age group are important. Objectives We aimed to study the associations of common genetic risk factors (i.e. the factor V Leiden and prothrombin G20210A mutations, non-O blood group and family history of VT) with risk of a first VT in older age (> 70 years). Methods Four hundred and one consecutive cases with a first-time thrombosis and 431 controls (all >= 70 years) were included in the AT-AGE case control study. Information on risk factors for VT, including family history of VT in first-degree relatives, was obtained by interview. Unprovoked VT was defined as thrombosis not related to surgery, fracture, plaster cast or immobility within 3 months prior to VT. Results The risk of VT was 2.2-fold increased in factor V Leiden carriers (95% confidence interval [CI], 1.2-3.9), 1.4-fold increased in prothrombin mutation carriers (95% CI, 0.5-3.9), and 1.3-fold increased in those with non-O blood group (95% CI, 1.0-1.8). Positive family history of VT was associated with a 2.1-fold increased risk of VT (95% CI, 1.5-3.1). The highest risk of VT was found in individuals who had both a positive family history and were carriers of one of the two prothrombotic mutations. Conclusions Genetic factors clearly related to VT in younger populations were also risk factors in older age and a positive family history was also important in this age group. PMID- 27377286 TI - Multicapillary gel electrophoresis based analysis of genetic variants in the WFS1 gene. AB - The WFS1 gene is one of the thoroughly investigated targets in diabetes research, variants of the gene were suggested to be the genetic components of the common forms (type 1 and type 2) of diabetes. Our project focused on the analysis of polymorphisms (rs4689388, rs148797429, rs4273545) localized in the WFS1 promoter region. Although submarine gel electrophoresis based approaches were also employed in the genetic tests, it was demonstrated that multicapillary electrophoresis offers a state of the art approach for reliable high-throughput SNP and VNTR analysis. Association studies were carried out in a case-control setup. Luciferase reporter assay was employed to test the effect of the investigated loci on the activity of gene expression in vitro. Significant association could be demonstrated between all three polymorphisms and type 2 diabetes in both allele- and genotype-wise settings even using Bonferroni correction. It is notable; however, that the three loci were in strong linkage disequilibrium, thus the observed associations cannot be considered as separate effects. Molecular analyses showed that the rs4273545 GT SNP played a role in the regulation of transcription in vitro. However, this effect took place only in the presence of the region including the rs148797429 site, although this latter locus did not have its own impact on the regulation of gene expression. The paper provides genotyping protocols readily applicable in any multiplex SNP and VNTR analyses, moreover confirms and extends previous results about the role of WFS1 polymorphisms in the genetic risk of diabetes mellitus. PMID- 27377287 TI - The application of phage-based faecal pollution markers to predict the concentration of adenoviruses in mussels (Mytilus edulis) and their overlying waters. AB - AIM: This study set out to determine whether phage-based indicators may provide a 'low-tech' alternative to existing approaches that might help maintain the microbial safety of shellfish and their overlying waters. METHODS AND RESULTS: Mussels and their overlying waters were collected biweekly from an estuary in southeast England over a 2-year period (May 2013-April 2015) (n = 48). Levels of bacterial indicators were determined using membrane filtration and most probable number methods and those of bacteriophages were determined by direct plaque assay. The detection of adenovirus was determined using real-time polymerase chain reaction. The results revealed that somatic coliphages demonstrated the most significant correlations with AdV F and G in mussels (rho = 0.55) and overlying waters (rho = 0.66), followed by GB124 phages (rho = 0.43) while Escherichia coli showed no correlation with AdV F and G in mussels. CONCLUSION: This study demonstrates that the use of somatic coliphages and GB124 phages may provide a better indication of the risk of adenovirus contamination of mussels and their overlying waters than existing bacterial indicators. SIGNIFICANCE AND IMPACT OF THE STUDY: Phage-based detection may be particularly advantageous in low-resource settings where viral infectious disease presents a significant burden to human health. PMID- 27377288 TI - Increased epidermal thickness and abnormal epidermal differentiation in keloid scars. AB - BACKGROUND: The pathogenesis underlying keloid formation is still poorly understood. Research has focused mostly on dermal abnormalities, while the epidermis has not yet been studied. OBJECTIVES: To identify differences within the epidermis of mature keloid scars compared with normal skin and mature normotrophic and hypertrophic scars. METHODS: Rete ridge formation and epidermal thickness were evaluated in tissue sections. Epidermal proliferation was assessed using immunohistochemistry (Ki67, keratins 6, 16 and 17) and with an in vitro proliferation assay. Epidermal differentiation was evaluated using immunohistochemistry (keratin 10, involucrin, loricrin, filaggrin, SPRR2, SKALP), reverse-transcriptase polymerase chain reaction (involucrin) and transmission electron microscopy (stratum corneum). RESULTS: All scars showed flattening of the epidermis. A trend of increasing epidermal thickness correlating to increasing scar abnormality was observed when comparing normal skin, normotrophic scars, hypertrophic scars and keloids. No difference in epidermal proliferation was observed. Only the early differentiation marker involucrin showed abnormal expression in scars. Involucrin was restricted to the granular layer in healthy skin, but showed panepidermal expression in keloids. Normotrophic scars expressed involucrin in the granular and upper spinous layers, while hypertrophic scars resembled normotrophic scars or keloids. Abnormal differentiation was associated with ultrastructural disorganization of the stratum corneum in keloids compared with normal skin. CONCLUSIONS: Keloids showed increased epidermal thickness compared with normal skin and normotrophic and hypertrophic scars. This was not due to hyperproliferation, but possibly caused by abnormal early terminal differentiation, which affects stratum corneum formation. Our findings indicate that the epidermis is associated with keloid pathogenesis and identify involucrin as a potential diagnostic marker for abnormal scarring. PMID- 27377289 TI - IMAGING DIAGNOSIS-ECTOPIC SPLEEN MIMICKING HEPATIC TUMOR WITH INTRA-ABDOMINAL METASTASES INVESTIGATED VIA TRIPLE-PHASE HELICAL COMPUTED TOMOGRAPHY IN A DOG. AB - A 10-year-old castrated male miniature dachshund was presented with an abdominal mass. The dog had a history of splenectomy. Triple-phase helical computed tomography was utilized, revealing a hepatic mass and multiple intra-abdominal solid masses. In triple-phase helical computed tomography the images, hepatic mass and two of four intra-abdominal masses were heterogenous in all phases. Therefore, we diagnosed a malignant hepatic tumor and presumed intra-abdominal metastases. The masses were surgically removed and were histologically composed of normal spleen tissues, findings which were consistent with ectopic spleen. PMID- 27377290 TI - Life events and escape in conversion disorder. AB - BACKGROUND: Psychological models of conversion disorder (CD) traditionally assume that psychosocial stressors are identifiable around symptom onset. In the face of limited supportive evidence such models are being challenged. METHOD: Forty-three motor CD patients, 28 depression patients and 28 healthy controls were assessed using the Life Events and Difficulties Schedule in the year before symptom onset. A novel 'escape' rating for events was developed to test the Freudian theory that physical symptoms of CD could provide escape from stressors, a form of 'secondary gain'. RESULTS: CD patients had significantly more severe life events and 'escape' events than controls. In the month before symptom onset at least one severe event was identified in 56% of CD patients - significantly more than 21% of depression patients [odds ratio (OR) 4.63, 95% confidence interval (CI) 1.56 13.70] and healthy controls (OR 5.81, 95% CI 1.86-18.2). In the same time period 53% of CD patients had at least one 'high escape' event - again significantly higher than 14% in depression patients (OR 6.90, 95% CI 2.05-23.6) and 0% in healthy controls. Previous sexual abuse was more commonly reported in CD than controls, and in one third of female patients was contextually relevant to life events at symptom onset. The majority (88%) of life events of potential aetiological relevance were not identified by routine clinical assessments. Nine per cent of CD patients had no identifiable severe life events. CONCLUSIONS: Evidence was found supporting the psychological model of CD, the Freudian notion of escape and the potential aetiological relevance of childhood traumas in some patients. Uncovering stressors of potential aetiological relevance requires thorough psychosocial evaluation. PMID- 27377291 TI - Physics-Inspired Micro/Nanotherapeutics: Same Problem, Different Approaches. PMID- 27377292 TI - Effects of two different exercise programs on chronic fatigue in lupus patients. AB - OBJECTIVES: Fatigue is a major complaint of patients with systemic lupus erythemasosus (SLE). While several studies have demonstrated the benefits of exercise, the effects of supervised training were never compared to those of home training. METHODS: Forty-five SLE patients suffering from fatigue, as defined by Krupp's fatigue severity scale (FSS) >= 3.7, were randomized in 3 groups: supervised training group (STG), home training group (HTG), and control group (CG). Primary outcome was the change in FSS at month 3. In parallel, we measured the physical working capacity measured at 75% of the predicted maximal heart rate (PWC75%/kg) and the modified Borg's scale to assess perception of exertion. RESULTS: Both STG and HTG, but not the CG, statistically improved their FSS at month 3. By contrast, the PWC75%/kg and the Borg's scale did not improve in none of the groups. Surprinsingly, compliance was similar and low (+/-50%) in both exercise groups. Moreover, less compliant patients improved their fatigue as much as more compliant patients. CONCLUSIONS: Patients included in the STG and the HTG similarly improved their fatigue, irrespectively of their level of compliance, raising the possibility that the beneficial effect on fatigue was not only exercise-related. PMID- 27377293 TI - L929 fibroblast bioassay on the in vitro toxicity of SnCl2, H3PO4, Clearfil SE primer and combinations thereof. AB - Stannous chloride (SnCl(2), 35%) can increase microtensile bond strength between a self-etching adhesive and dental hard tissue either alone or in combination with phosphoric acid (H(3)PO(4), 35%). Whereas cell toxicity of H(3)PO(4) has been sufficiently investigated, little is known about the toxicity of concentrated SnCl(2). The present study determined the in vitro toxicity of SnCl(2), H(3)PO(4), the primer of a self-etching adhesive (Clearfil SE) and combinations thereof at three concentrations (0.01%?0.3%) in a L929 fibroblast bioassay. Cell viability was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) assay, the integrity of cell membranes was visualised by trypan blue staining (cell necrosis assay). Cell viability was impaired at concentrations between 0.09% and 0.13% for SnCl(2), between 0.06% and 0.09% for H(3)PO(4), and between 0.19% and 0.29% for Clearfil SE primer. Combinations of agents showed additive toxic effects. SnCl(2) showed a slightly lower but comparable in vitro toxicity to H(3)PO(4), which gives a perspective for further in vitro, in situ and clinical studies on this issue, and for the intraoral use of SnCl(2) to increase bond strength between an adhesive system and both enamel and dentine. PMID- 27377294 TI - Spirituality and mood pathology in severe skin conditions: a prospective observational study. AB - Although the association between spirituality and parameters of psychological health and disease has been investigated extensively, little evidence is available for its potential role in dermatology. In a single-centre observational prospective study, 149 outpatients (107 women) with systemic sclerosis (SSc; n = 44), lupus erythematosus (LE; n = 48), or early stage malignant melanoma (MM; n = 57) were investigated using the multidimensional inventory for religious/spiritual well-being together with the Brief Symptom Inventory for psychiatric symptoms (BSI-18). SSc patients reported the highest amount of Somatization in comparison with LE and MM patients (p < 0.05). Furthermore, in line with the previous research, spiritual dimensions, such as Hope for a better future (p < 0.01) or Hope for a better afterlife (p < 0.01), proved to be especially negatively predictive for the global amount of psychiatric symptom burden in these dermatological patient groups. Our findings suggest that greater attention should be given to spiritual issues, such as encouraging patients, imbuing them with optimism, and offering interventions that address spiritual well-being. PMID- 27377295 TI - Role of F225 in O-phosphoserine sulfhydrylase from Aeropyrum pernix K1. AB - O-Phosphoserine sulfhydrylase (OPSS) synthesizes cysteine from O-phospho-L-serine (OPS) and sulfide. We have determined the three-dimensional structures of OPSS from hyperthermophilic archaeon Aeropyrum pernix K1 (ApOPSS) in complex with aminoacrylate intermediate (AA) formed from pyridoxal 5'-phosphate with OPS or in complex with cysteine and compared them with that of ApOPSS. We found an orientational change of F225 at the active-site entrance and constructed an F225A mutant to examine its activities and AA stability and clarify the role of F225 in ApOPSS. The OPS and O-acetyl-L-serine (OAS) sulfhydrylase activities of the F225A mutant decreased by 4.2- and 15-fold compared to those of the wild-type (wt) ApOPSS, respectively. The ability of OPS and OAS to form AA also decreased by 12- and 27-fold, respectively. AA was less stable in the F225A mutant than in the wt ApOPSS. Simulated docking showed that leaving groups, such as phosphate and acetate, were oriented to the inside of the active site in the F225A mutant, whereas they were oriented to the entrance in the wt ApOPSS. These results suggest that F225 in ApOPSS plays important roles in maintaining the hydrophobic environment of AA from solvent water and in controlling the orientation of leaving groups. PMID- 27377296 TI - Crystal structure of a putative oligopeptide-binding periplasmic protein from a hyperthermophile. AB - Oligopeptide-binding proteins (Opps) are part of the ATP-binding cassette system, playing a crucial role in nutrient uptake and sensing the external environment in bacteria, including hyperthermophiles. Opps serve as a binding platform for diverse peptides; however, how these peptides are recognized by Opps is still largely unknown and few crystal structures of Opps from hyperthermophiles have been determined. To facilitate such an understanding, the crystal structure of a putative Opp, OppA from Thermotoga maritima (TmOppA), was solved at 2.6-A resolution in the open conformation. TmOppA is composed of three domains. The N terminal domain consists of twelve strands, nine helices, and four 310 helices, and the C-terminal domain consists of five strands, ten helices, and one 310 helix. These two domains are connected by the linker domain, which consists of two strands, three helices, and three 310 helices. Based on structural comparisons of TmOppA with other OppAs and binding studies, we suggest that TmOppA might be a periplasmic Opp. The most distinct feature of TmOppA is the insertion of two helices, which are lacking in other OppAs. A cavity volume between the N-terminal and C-terminal domains is suggested to be responsible for binding peptides of various lengths. PMID- 27377297 TI - Anti-phospholipid Antibodies and Smoking: An Overview. AB - Antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies, specifically lupus anticoagulant, anticardiolipin antibodies, and anti-beta2 glycoprotein-I antibodies. Antiphospholipid syndrome can occur on its own or in association with other autoimmune diseases, most commonly systemic lupus erythematosus (SLE). A connection between cigarette smoking and anti phospholipid antibodies (aPL) was first reported in the late1980s. Systemic lupus erythematosus patients with aPL are more likely to be smokers than those without aPL. These patients have a particularly high frequency of vascular events. Recently, a potential link between periodontitis, tobacco, and aPL has been proposed. Research has also suggested that periodontitis and Porphyromonas gingivalis infection are associated with citrullination through the action of peptidylarginine deiminase. A strong correlation between smoking and the presence of citrillunated autoantibodies, which are characteristic of rheumatoid arthritis, has also been observed. While many studies have investigated possible links between infection and aPL in patients with autoimmune diseases, the association of smoking with aPL has not been systematically examined. The fact that both aPL and tobacco are risk factors for thrombosis has complicated efforts to evaluate these factors separately. Also, there has been great variability in measurement techniques, and laboratories lack routine methods for differentiating transient and persistent aPL; both of these factors can make interpretation of autoantibody results quite challenging. This review summarizes the clinical evidence supporting a posited link between aPL and smoking, both in patients with a systemic autoimmune disease and in patients with other medical conditions. PMID- 27377298 TI - Bacterial and Viral Infections in Atopic Dermatitis: a Comprehensive Review. AB - Atopic dermatitis (AD) is the most common allergic skin disease in the general population. It is a chronic inflammatory skin disease complicated by recurrent bacterial and viral infections that, when left untreated, can lead to significant complications. The current article will review immunologic and molecular mechanisms underlying the propensity of AD patients to microbial infections. These infections include Staphylococcus aureus (S. aureus) skin infections, eczema herpeticum, eczema vaccinatum, and eczema coxsackium. Previous studies have shown that skin barrier defects, a decrease in antimicrobial peptides, increased skin pH, or Th2 cytokines such as IL-4 and IL-13 are potential contributing factors for the increased risk of skin infections in AD. In addition, bacterial virulence such as methicillin-resistant S. aureus (MRSA) produces significantly higher number of superantigens that increase their potential in causing infection and more severe cutaneous inflammation in AD patients. More recent studies suggest that skin microbiome including Staphylococcus epidermidis or other coagulase-negative staphylococci may play an important role in controlling S. aureus skin infections in AD. Other studies also suggest that genetic variants in the innate immune response may predispose AD patients to increased risk of viral skin infections. These genetic variants include thymic stromal lymphopoietin (TSLP), type I interferon (alpha, beta, omega), type II interferon (gamma), and molecular pathways that lead to the production of interferons (interferon regulatory factor 2). A common staphylococcal toxin, alpha-toxin, may also play a role in enhancing herpes simplex virus skin infections in AD. Further understanding of these disease processes may have important clinical implications for the prevention and treatment of skin infections in this common skin disease. PMID- 27377300 TI - The splanchnic anti-inflammatory pathway: could it be the efferent arm of the inflammatory reflex? AB - What is the topic of this review? We review the current literature on the neural reflex termed the 'inflammatory reflex' that inhibits an excessive release of inflammatory mediators in response to an immune challenge. What advances does it highlight? The original model proposed that the inflammatory reflex is a vago vagal reflex that controls immune function. We posit that, in the endotoxaemic animal model, the vagus nerves do not appear to play a role. The evidence suggests that the efferent motor pathway, termed here the 'splanchnic anti inflammatory pathway', is purely sympathetic, travelling via the greater splanchnic nerves to regulate the ensuing inflammatory response to immune challenges. Exposure to immune challenges results in the development of inflammation. An insufficient inflammatory response can be life-threatening, whereas an exaggerated response is also detrimental because it causes tissue damage and, in extreme cases, septic shock that can lead to death. Hence, inflammation must be finely regulated. It is generally accepted that the brain inhibits inflammation induced by an immune challenge in two main ways: humorally, by activating the hypothalamic-pituitary-adrenal axis to release glucocorticoids; and neurally, via a mechanism that has been termed the 'inflammatory reflex'. The efferent arm of this reflex (the neural-to-immune link) was thought to be the 'cholinergic anti-inflammatory pathway'. Here, we discuss data that support the hypothesis that the vagus nerves play no role in the control of inflammation in the endotoxaemic animal model. We have shown and posit that it is the greater splanchnic nerves that are activated in response to the immune challenge and that, in turn, drive postganglionic sympathetic neurons to inhibit inflammation. PMID- 27377299 TI - The use of intracranial recordings to decode human language: Challenges and opportunities. AB - Decoding speech from intracranial recordings serves two main purposes: understanding the neural correlates of speech processing and decoding speech features for targeting speech neuroprosthetic devices. Intracranial recordings have high spatial and temporal resolution, and thus offer a unique opportunity to investigate and decode the electrophysiological dynamics underlying speech processing. In this review article, we describe current approaches to decoding different features of speech perception and production - such as spectrotemporal, phonetic, phonotactic, semantic, and articulatory components - using intracranial recordings. A specific section is devoted to the decoding of imagined speech, and potential applications to speech prosthetic devices. We outline the challenges in decoding human language, as well as the opportunities in scientific and neuroengineering applications. PMID- 27377301 TI - Five-year follow-up of polymer-free sirolimus- and probucol-eluting stents versus new generation zotarolimus-eluting stents in patients presenting with st elevation myocardial infarction. AB - BACKGROUND: Patients with ST-segment elevation myocardial infarction (STEMI) undergoing drug-eluting stent (DES) implantation are at increased risk of late adverse events, partly explained by an exaggerated inflammatory reaction to durable-polymer stent coatings. OBJECTIVES: We sought to investigate whether implantation of polymer-free DES would reduce this risk. METHODS: In the ISAR TEST 5 (the Intracoronary Stenting and Angiographic Results: Test Efficacy of Sirolimus- and Probucol- and Zotarolimus-Eluting Stents) trial, patients were randomly allocated to receive a polymer-free sirolimus- and probucol-eluting stent or a new generation durable-polymer zotarolimus-eluting stent. We analyzed late clinical outcomes in the subgroup of patients presenting with STEMI. The primary endpoint was the combined incidence of cardiac death, target vessel related myocardial infarction or target lesion revascularization at 5 years. RESULTS: 311 patients with STEMI were randomized to receive sirolimus- and probucol-eluting stents (n = 215) or zotarolimus-eluting stents (n = 96). At 5 years, there was no difference in the incidence of the primary endpoint in patients treated with sirolimus- and probucol-eluting stents versus zotarolimus eluting stents (18.3% versus 20.1% respectively, hazard ratio = 0.87, 95% CI, 0.50-1.51; P = 0.62). Rates of the individual components of the primary endpoint were also comparable in both groups. The incidence of definite/probable stent thrombosis was 1.4% versus 1.0% respectively (hazard ratio = 1.35, 95% CI, 0.14 12.94, P = 0.80). CONCLUSIONS: Long-term outcomes of patients with STEMI treated with polymer-free sirolimus- and probucol-eluting stents versus durable-polymer zotarolimus-eluting stents were similar. Stent thrombosis rates were low and comparable in both treatment groups, with no events beyond 12 months. CLINICAL TRIAL REGISTRATION: Registered at ClinicalTrials.gov (Identifier NCT 00598533) (c) 2016 Wiley Periodicals, Inc. PMID- 27377302 TI - Electroacupuncture at Zusanli (ST36) ameliorates colonic neuronal nitric oxide synthase upregulation in rats with neurogenic bowel dysfunction following spinal cord injury. AB - Study designExperimental study.ObjectiveTo determine the effects of electroacupuncture (EA) at Zusanli (ST36) on colonic motility and neuronal nitric oxide synthase (nNOS) expression in rats with neurogenic bowel dysfunction (NBD) after spinal cord injury (SCI).SettingSecond School of Clinical Medical, Nanjing University of Chinese Medicine, Jiangsu, China.MethodsWe divided 30 adult Sprague Dawley rats into a sham group (10 rats), a model group (SCI alone, 10 rats) and a EA group (SCI+EA at ST36, 10 rats). Defecation time was recorded as the time from activated carbon administration (on day 15) to evacuation of the first black stool. Immunohistochemical, real-time PCR and western blot analyses were performed to assess changes in nNOS-immunoreactive cells, and nNOS messenger RNA (mRNA) and protein, respectively, after 14 experimental days.ResultsDefecation time was lower in the EA group than in the model group (P<0.01). On immunohistochemical analysis, nNOS was localized in the myenteric plexus of the colon. The number of nNOS-immunoreactive cells and the intensity of nNOS staining were greater in the model group than in the sham group and lesser in the EA group than in the model group. Consistent with the immunohistochemical findings, nNOS mRNA and protein expression was higher in the model group than in the sham group and lower in the EA group than in the model group (P<0.05 for both).ConclusionIncreased colonic nNOS expression can induce/aggravate NBD in SCI rats. EA at ST36 ameliorated NBD, possibly by downregulating colonic nNOS expression. PMID- 27377303 TI - Cardiovascular disease risk in people with spinal cord injury: is there a possible association between reduced lung function and increased risk of diabetes and hypertension? AB - STUDY DESIGN: Retrospective, descriptive study of medical files 253 patients with chronic traumatic spinal cord injury (SCI). OBJECTIVES: To determine the frequency of cardiovascular disease (CVD) risk factors in SCI people, to estimate CVD risk in this population according to the Framingham Risk Score (FRS) and to determine whether reduced lung function parameters are significant predictors of diabetes mellitus (DM) and hypertension. SETTING: Academic Rehabilitation Hospital. METHODS: Demographic and clinical records of the patients and lung function parameters were obtained. RESULTS: The FRS could not be calculated in 26 (10.3%) patients because this tool is designed for adults aged 20 years and older. According to the FRS guideline, ~6.7% of the SCI patients had high risk, 5.9% of them had intermediate risk and 77.1% of the study group had low risk for CVD. Regression analysis showed that impaired lung function parameters (FEV1, FVC and MVV) were significant predictors for the future development of hypertension (odds ratio (OR): 0.483 (0.258-0.903 95% confidence interval (CI)), OR: 0.549 (0.319-0.946 95% CI) and OR: 0.981 (0.965-0.998 95% CI), respectively) and DM (OR: 0.335 (0.140-0.801 95% CI), OR: 0.391 (0.183-0.839 95% CI) and OR: 0.970 (0.947-0.993 95% CI), respectively) in the SCI population. CONCLUSION: This study showed that there might be a significant relationship between reduced lung function and the risk of DM and hypertension in people with SCI. Therefore, systematic measurement of these parameters should be performed in the routine clinical follow-up of SCI patients. Once reduced lung parameters are determined, the higher risk for developing hypertension and DM should be considered. PMID- 27377304 TI - Exploratory study to suggest the possibility of MMP-8 and MMP-9 serum levels as early markers for remission after traumatic spinal cord injury. AB - STUDY DESIGN: A prospective observational study reporting the correlation between matrix metalloprotein serum levels and remission after traumatic spinal cord injury (SCI). OBJECTIVES: To investigate serum cytokine levels as predictive markers. SETTING: Germany, Rhineland-Palatinate (Rheinland-Pfalz). METHODS: Between 2010 and 2015, data sets from 115 patients (33 female, 82 male) after traumatic SCI were recorded at the BG Trauma Centre Ludwigshafen. We examined the serum levels of Matix metallopraoteinases (MMPs) MMP-2, MMP-8, MMP-9, MMP-10 and MMP-12 over a 12-week period, that is, at admission and 4, 9, 12 h, 1 and 3 days and 1, 2, 4, 8 and 12 weeks after trauma. Following the same match-pair procedure as in our previous studies, we selected 10 patients with SCI and neurological remission (Group 1) and 10 patients with an initial American Spinal Injury Association (ASIA) A grade and no neurological remission (Group 0). Ten patients with an isolated vertebral fracture without neurological deficits served as a control group (Group C). Our analysis was performed using a Luminex Performance Human High Sensitivity Cytokine Panel. Multivariate logistic regression models were used to examine the predictive value of MMPs with respect to neurological remission vs no neurological remission. RESULTS: MMP-8 and MMP-9 provided significantly different values. The favoured predictive model allows to differentiate between neurological remission and no neurological remission in 97% of cases. CONCLUSIONS: The results indicate that further studies with an enlarged collective are warranted in order to investigate current monitoring, prognostic and tracking techniques as well as scoring systems. PMID- 27377305 TI - Mechanistic insights into chemical and photochemical transformations of bismuth vanadate photoanodes. AB - Artificial photosynthesis relies on the availability of semiconductors that are chemically stable and can efficiently capture solar energy. Although metal oxide semiconductors have been investigated for their promise to resist oxidative attack, materials in this class can suffer from chemical and photochemical instability. Here we present a methodology for evaluating corrosion mechanisms and apply it to bismuth vanadate, a state-of-the-art photoanode. Analysis of changing morphology and composition under solar water splitting conditions reveals chemical instabilities that are not predicted from thermodynamic considerations of stable solid oxide phases, as represented by the Pourbaix diagram for the system. Computational modelling indicates that photoexcited charge carriers accumulated at the surface destabilize the lattice, and that self passivation by formation of a chemically stable surface phase is kinetically hindered. Although chemical stability of metal oxides cannot be assumed, insight into corrosion mechanisms aids development of protection strategies and discovery of semiconductors with improved stability. PMID- 27377308 TI - Better working environments could boost recruitment to anaesthesia, says study. PMID- 27377307 TI - Knockdown of Pentraxin 3 suppresses tumorigenicity and metastasis of human cervical cancer cells. AB - Pentraxin 3 (PTX3) as an inflammatory molecule has been shown to be involved in immune response, inflammation, and cancer. However, the effects of PTX3 on the biological features of cervical cancer cells in vitro and in vivo have not been delineated. Immunohistochemical staining showed that increased PTX3 expression was significantly associated with tumor grade (P < 0.011) and differentiation (P < 0.019). Knocking down PTX3 with lentivirus-mediated small hairpin RNA (shRNA) in cervical cancer cell lines resulted in inhibited cell viability, diminished colony-forming ability, and induced cell cycle arrest at the G2/M phase of the cell cycle, along with downregulated expression of cyclin B1, cdc2, and cdc25c, and upregulated expression of p-cdc2, p-cdc25c, p21, and p27. Furthermore, knockdown of PTX3 significantly decreased the potential of migration and invasion of cervical cancer cells by inhibiting matrix metalloproteidase-2 (MMP-2), MMP-9, and urokinase plasminogen activator (uPA). Moreover, in vivo functional studies showed PTX3-knockdown in mice suppressed tumorigenicity and lung metastatic potential. Conversely, overexpression of PTX3 enhanced proliferation and invasion both in vitro and in vivo. Our results demonstrated that PTX3 contributes to tumorigenesis and metastasis of human cervical cancer cells. Further studies are warranted to demonstrate PTX3 as a novel therapeutic biomarker for human cervical cancer. PMID- 27377309 TI - A Qualitative Study of Physician Perspectives on Prognostication in Neonatal Hypoxic Ischemic Encephalopathy. AB - Hypoxic ischemic encephalopathy is the most frequent cause of neonatal encephalopathy and yields a great degree of morbidity and mortality. From an ethical and clinical standpoint, neurological prognosis is fundamental in the care of neonates with hypoxic ischemic encephalopathy. This qualitative study explores physician perspectives about neurological prognosis in neonatal hypoxic ischemic encephalopathy. This study aimed, through semistructured interviews with neonatologists and pediatric neurologists, to understand the practice of prognostication. Qualitative thematic content analysis was used for data analysis. The authors report 2 main findings: (1) neurological prognosis remains fundamental to quality-of-life predictions and considerations of best interest, and (2) magnetic resonance imaging is presented to parents with a greater degree of certainty than actually exists. Further research is needed to explore both the parental perspective and, prospectively, the impact of different clinical approaches and styles to prognostication for neonatal hypoxic ischemic encephalopathy. PMID- 27377310 TI - LOCC indistinguishable orthogonal product quantum states. AB - We construct two families of orthogonal product quantum states that cannot be exactly distinguished by local operation and classical communication (LOCC) in the quantum system of (2k+i) ? (2l+j) (i, j ? {0, 1} and i >= j ) and (3k+i) ? (3l+j) (i, j ? {0, 1, 2}). And we also give the tiling structure of these two families of quantum product states where the quantum states are unextendible in the first family but are extendible in the second family. Our construction in the quantum system of (3k+i) ? (3l+j) is more generalized than the other construction such as Wang et al.'s construction and Zhang et al.'s construction, because it contains the quantum system of not only (2k) ? (2l) and (2k+1) ? (2l) but also (2k) ? (2l+1) and (2k+1) ? (2l+1). We calculate the non-commutativity to quantify the quantumness of a quantum ensemble for judging the local indistinguishability. We give a general method to judge the indistinguishability of orthogonal product states for our two constructions in this paper. We also extend the dimension of the quantum system of (2k) ? (2l) in Wang et al.'s paper. Our work is a necessary complement to understand the phenomenon of quantum nonlocality without entanglement. PMID- 27377314 TI - Editorial. PMID- 27377311 TI - Physiologically-based pharmacokinetic modeling to predict the clinical pharmacokinetics of monoclonal antibodies. AB - Accurate prediction of the clinical pharmacokinetics of new therapeutic entities facilitates decision making during drug discovery, and increases the probability of success for early clinical trials. Standard strategies employed for predicting the pharmacokinetics of small-molecule drugs (e.g., allometric scaling) are often not useful for predicting the disposition monoclonal antibodies (mAbs), as mAbs frequently demonstrate species-specific non-linear pharmacokinetics that is related to mAb-target binding (i.e., target-mediated drug disposition, TMDD). The saturable kinetics of TMDD are known to be influenced by a variety of factors, including the sites of target expression (which determines the accessibility of target to mAb), the extent of target expression, the rate of target turnover, and the fate of mAb-target complexes. In most cases, quantitative information on the determinants of TMDD is not available during early phases of drug discovery, and this has complicated attempts to employ mechanistic mathematical models to predict the clinical pharmacokinetics of mAbs. In this report, we introduce a simple strategy, employing physiologically-based modeling, to predict mAb disposition in humans. The approach employs estimates of inter-antibody variability in rate processes of extravasation in tissues and fluid-phase endocytosis, estimates for target concentrations in tissues derived through use of categorical immunohistochemical scores, and in vitro measures of the turnover of target and target-mAb complexes. Monte Carlo simulations were performed for four mAbs (cetuximab, figitumumab, dalotuzumab, trastuzumab) directed against three targets (epidermal growth factor receptor, insulin-like growth factor receptor 1, human epidermal growth factor receptor 2). The proposed modeling strategy was able to predict well the pharmacokinetics of cetuximab, dalotuzumab, and trastuzumab at a range of doses, but trended towards underprediction of figitumumab concentrations, particularly at high doses. The general agreement between model predictions and experimental observations suggests that PBPK modeling may be useful for the a priori prediction of the clinical pharmacokinetics of mAb therapeutics. PMID- 27377312 TI - Understanding Multiple Behavioral Risk Factors for Cancer in Rural Women. AB - OBJECTIVES: To examine the demographic and health-related factors associated with risk behaviors that have been linked to cancer including smoking, high BMI, and low physical activity. DESIGN AND SAMPLE: A secondary analysis was conducted using data from Rural Families Speak about Health, a multistate, epidemiologic study of rural American women and their families (N = 444). MEASURES: Validated measures for various demographic and health-related items including tobacco use, BMI, physical activity, and depression were used. RESULTS: Of the total sample with complete data (n = 399), the mean age was 32 years and the majority were White (64%), married (67%), had a high school education or higher (73%), and had an annual household income of less than $40,000 (90%). Regarding cancer risk behaviors, 36% of the sample were smokers, 39% reported low levels of physical activity, and 45% had a calculated BMI over 30. Thirty-five percent of participants reported engaging in two or more risk behaviors. There were significant differences in income, perceived health status, and depression depending on the number of risk behaviors reported. CONCLUSIONS: Understanding combinations of risk behaviors can assist nurses and other health professionals in tailoring multiple health behavior change interventions to prevent cancer among rural women. PMID- 27377315 TI - Purulent Thyroiditis-a Clinical Study of 5 Cases. AB - Between 1 January 1990 and 31 December 2006, 13279 patients were operated on due to various forms of goitre, of which five cases were diagnosed with purulent thyroiditis-one child aged 8, three women and one man all between 35 and 81 years of age. The course of the disease was unusual. In three of the patients cancer was suspected. In all of the patients hard nodules were discovered within the thyroid gland, ultrasonographically heterogeneous and hypo-echogenic, although scintigraphic examination showed "cold" nodules. The child presented regional lymph node enlargement. Except in one case, all patients were apyretic. The rapid growth of the thyroid gland and symptoms of compression were observed in 2 cases. In one of them, trache-ostomy was required. Fine needle aspiration biopsy of the thyroid gland revealed the presence of profuse purulent infiltration in one case. Neither thyroid dysfunction nor autoimmune changes were detected. A subtotal thyroidectomy was performed in all patients. In the paediatric case, the enlarged lymph nodes were also resected. In 3 cases, thyroid abscess was diagnosed and drained and staphylococcus epidermidis, streptococcus epidermidis and streptococcus pyogenes were found. Microscopic examination proved the presence of aspergillus fumigatus in one case. Antibiotic therapy was applied postoperatively and all the patients recovered. CONCLUSIONS: 1. The clinical course of purulent thyroiditis leads to a diagnostic challenge. The surgical treatment of purulent thyroiditis allows for a faster recovery for the patient. PMID- 27377316 TI - Insights into Chronic Functional Movement Disorders: The Value of Qualitative Psychiatric Interviews. AB - BACKGROUND: Patients with functional movement disorders (FMDs) are commonly seen by neurologists and psychosomatic medicine psychiatrists. Research literature provides scant information about the subjective experiences of individuals with this often chronic problem. OBJECTIVE: To enhance our understanding of psychologic aspects of FMDs by conducting qualitative interviews of research subjects. METHODS: In total, 36 patients with FMDs were recruited from the Human Motor Control clinic at the National Institutes of Health. Each subject participated in a qualitative psychiatric interview and a structured diagnostic psychiatric interview. RESULTS: Of our 36 subjects, 28 had current or lifetime psychiatric disorders in addition to conversion disorder and 22 had current disorders. Qualitative interviews provided rich information on patients' understanding of their illnesses and impaired cognitive processing of emotions. CONCLUSION: Our study supports the addition of open-ended qualitative interviews to delineate emotional dynamics and conceptual frameworks among such patients. Exploratory interviews generate enhanced understanding of such complex patients, above and beyond that gained by assessing DSM diagnostic comorbidities. PMID- 27377317 TI - A dinosaurian facial deformity and the first occurrence of ameloblastoma in the fossil record. AB - Despite documentation of various types of neoplastic pathologies encountered in the vertebrate fossil record, no ameloblastic tumours have been recognised so far. Ameloblastoma is a benign neoplasic tumour with a strong preponderance for the mandible. Here, we report for the first time the presence of an ameloblastoma neoplasm in the lower jaw of a specimen referred to the derived non-hadrosaurid hadrosauroid dinosaur Telmatosaurus transsylvanicus from the uppermost Cretaceous of the Haeg Basin in Romania. The location, external appearance and internal structure of the pathological outgrowth provide clear evidence for the diagnosis of ameloblastoma in Telmatosaurus. This report extends the range of pathologies encountered in hadrosauroid dinosaurs. In addition, recognition of an ameloblastoma neoplasm in a taxon lying close to the origin of 'duck-billed' hadrosaurid dinosaurs confirms the predisposition of this clade towards neoplasia pathologies already in its basal members. PMID- 27377318 TI - Response: Commentary: Past, present and future of epigenetics applied to livestock breeding. PMID- 27377319 TI - Neuropeptide Y (NPY) and posttraumatic stress disorder (PTSD): A translational update. AB - Posttraumatic stress disorder (PTSD) is a trauma-evoked syndrome, with variable prevalence within the human population due to individual differences in coping and resiliency. In this review, we discuss evidence supporting the relevance of neuropeptide Y (NPY), a stress regulatory transmitter in PTSD. We consolidate findings from preclinical, clinical, and translational studies of NPY that are of relevance to PTSD with an attempt to provide a current update of this area of research. NPY is abundantly expressed in forebrain limbic and brainstem areas that regulate stress and emotional behaviors. Studies in rodents demonstrate a role for NPY in stress responses, anxiety, fear, and autonomic regulation, all relevant to PTSD symptomology. Genetic studies support an association of NPY polymorphisms with stress coping and affect. Importantly, cerebrospinal fluid (CSF) measurements in combat veterans provide direct evidence of NPY association with PTSD diagnosis and symptomology. In addition, NPY involvement in pain, depression, addiction, and metabolism may be relevant to comorbidities associated with PTSD. Collectively, the literature supports the relevance of NPY to PTSD pathophysiology, although knowledge gaps remain. The NPY system is an attractive target in terms of understanding the physiological basis of PTSD as well as treatment of the disorder. PMID- 27377320 TI - Epigenetics changes caused by the fusion of human embryonic stem cell and ovarian cancer cells. AB - To observe the effect of gene expression and tumorigenicity in hybrid cells of human embryonic stem cells (hESCs) and ovarian cancer cells in vitro and in vivo using a mouse model, and to determine its feasibility in reprogramming tumour cells growth and apoptosis, for a potential exploration of the role of hESCs and tumour cells fusion in the management of ovarian cancer. Stable transgenic hESCs (H1) and ovarian cancer cell line OVCAR-3 were established before fusion, and cell fusion system was established to analyse the related indicators. PTEN expression in HO-H1 cells was higher than those in the parental stem cells and lower than those in parental tumour cells; the growth of OV-H1 (RFP+GFP) hybrid cells with double fluorescence expressions were obviously slower than that of human embryonic stem cells and OVCAR-3 ovarian cancer cells. The apoptosis signal of the OV-H1 hybrid cells was significantly higher than that of the hESCs and OVCAR-3 ovarian cancer cells. In vivo results showed that compared with 7 days, 28 days and 35 days after inoculation of OV-H1 hybrid cells; also, apoptotic cell detection indicated that much stronger apoptotic signal was found in OV-H1 hybrid cells inoculated mouse. The hESCs can inhibit the growth of OVCAR-3 cells in vitro by suppressing p53 and PTEN expression to suppress the growth of tumour that may be achieved by inducing apoptosis of OVCAR-3 cells. The change of epigenetics after fusion of ovarian cancer cells and hESCs may become a novel direction for treatment of ovarian cancer. PMID- 27377321 TI - Tau pathology in Creutzfeldt-Jakob disease revisited. AB - Creutzfeldt-Jakob disease (CJD) is a human prion disease with different etiologies. To determine the spectrum of tau pathologies in CJD, we assessed phospho-Tau (pTau) immunoreactivities in 75 sporadic CJD cases including an evaluation of the entorhinal cortex and six hippocampal subregions. Twelve cases (16%) showed only small tau-immunoreactive neuritic profiles. Fifty-two (69.3%) showed additional tau pathology in the medial temporal lobe compatible with primary age related tauopathy (PART). In 22/52 cases the lower pTau immunoreactivity load in the entorhinal cortex as compared to subiculum, dentate gyrus or CA4 region of the hippocampus was significantly different from the typical distribution of the Braak staging. A further 11 cases (14.7%) showed widespread tau pathologies compatible with features of primary tauopathies or the gray matter type of ageing-related tau astrogliopathy (ARTAG). Prominent gray matter ARTAG was also observed in two out of three additionally examined V203I genetic CJD cases. Analysis of cerebrospinal fluid revealed prominent increase of total tau protein in cases with widespread tau pathology, while pTau (T181) level was increased only in four. This correlated with immunohistochemical observations showing less pathology with anti-pTau T181 antibody when compared to anti-pTau S202/T205, T212/S214 and T231. The frequency of tau pathologies is not unusually high in sporadic CJD and does not precisely relate to PrP deposition. However, the pattern of hippocampal tau pathology often deviates from the stages of Braak. Currently applied examination of cerebrospinal fluid pTau (T181) level does not reliably reflect primary tauopathies, PART and ARTAG seen in CJD brains. PMID- 27377322 TI - PhyPA: Phylogenetic method with pairwise sequence alignment outperforms likelihood methods in phylogenetics involving highly diverged sequences. AB - While pairwise sequence alignment (PSA) by dynamic programming is guaranteed to generate one of the optimal alignments, multiple sequence alignment (MSA) of highly divergent sequences often results in poorly aligned sequences, plaguing all subsequent phylogenetic analysis. One way to avoid this problem is to use only PSA to reconstruct phylogenetic trees, which can only be done with distance based methods. I compared the accuracy of this new computational approach (named PhyPA for phylogenetics by pairwise alignment) against the maximum likelihood method using MSA (the ML+MSA approach), based on nucleotide, amino acid and codon sequences simulated with different topologies and tree lengths. I present a surprising discovery that the fast PhyPA method consistently outperforms the slow ML+MSA approach for highly diverged sequences even when all optimization options were turned on for the ML+MSA approach. Only when sequences are not highly diverged (i.e., when a reliable MSA can be obtained) does the ML+MSA approach outperforms PhyPA. The true topologies are always recovered by ML with the true alignment from the simulation. However, with MSA derived from alignment programs such as MAFFT or MUSCLE, the recovered topology consistently has higher likelihood than that for the true topology. Thus, the failure to recover the true topology by the ML+MSA is not because of insufficient search of tree space, but by the distortion of phylogenetic signal by MSA methods. I have implemented in DAMBE PhyPA and two approaches making use of multi-gene data sets to derive phylogenetic support for subtrees equivalent to resampling techniques such as bootstrapping and jackknifing. PMID- 27377323 TI - Estimating Influenza Outbreaks Using Both Search Engine Query Data and Social Media Data in South Korea. AB - BACKGROUND: As suggested as early as in 2006, logs of queries submitted to search engines seeking information could be a source for detection of emerging influenza epidemics if changes in the volume of search queries are monitored (infodemiology). However, selecting queries that are most likely to be associated with influenza epidemics is a particular challenge when it comes to generating better predictions. OBJECTIVE: In this study, we describe a methodological extension for detecting influenza outbreaks using search query data; we provide a new approach for query selection through the exploration of contextual information gleaned from social media data. Additionally, we evaluate whether it is possible to use these queries for monitoring and predicting influenza epidemics in South Korea. METHODS: Our study was based on freely available weekly influenza incidence data and query data originating from the search engine on the Korean website Daum between April 3, 2011 and April 5, 2014. To select queries related to influenza epidemics, several approaches were applied: (1) exploring influenza-related words in social media data, (2) identifying the chief concerns related to influenza, and (3) using Web query recommendations. Optimal feature selection by least absolute shrinkage and selection operator (Lasso) and support vector machine for regression (SVR) were used to construct a model predicting influenza epidemics. RESULTS: In total, 146 queries related to influenza were generated through our initial query selection approach. A considerable proportion of optimal features for final models were derived from queries with reference to the social media data. The SVR model performed well: the prediction values were highly correlated with the recent observed influenza-like illness (r=.956; P<.001) and virological incidence rate (r=.963; P<.001). CONCLUSIONS: These results demonstrate the feasibility of using search queries to enhance influenza surveillance in South Korea. In addition, an approach for query selection using social media data seems ideal for supporting influenza surveillance based on search query data. PMID- 27377325 TI - Extramedullary haematopoiesis: radiological imaging features. AB - Extramedullary haematopoiesis (EMH) is defined as the production of blood cells outside of the bone marrow, which occurs when there is inadequate production of blood cells. The most common causes of EMH are myelofibrosis, diffuse osseous metastatic disease replacing the bone marrow, leukaemia, sickle cell disease, and thalassemia. The purpose of this article is to review the common and uncommon imaging appearances of EMH by anatomical compartment. In the thorax, EMH most commonly presents as paravertebral fat-containing masses, and typically does not present a diagnostic dilemma; however, EMH in the abdomen most commonly manifests as hepatosplenomegaly with or without focal soft-tissue masses in the liver, spleen, perirenal space, and in the peritoneum. Hepatosplenomegaly, a non specific feature, most often occurs without an associated focal mass, which makes suggestion of EMH difficult. EMH manifesting as visceral soft-tissue masses often requires biopsy as the differential diagnosis can include lymphoma, metastatic disease, and sarcoma. Many of these soft-tissue masses do not contain adipose elements, making the diagnosis of EMH difficult. Clinical history is crucial, as EMH would likely not otherwise be in the differential in patients with non specific abdominal masses. Careful biopsy planning is necessary when EMH is a diagnostic consideration, given the propensity for haemorrhage. Understanding the typical imaging appearances of EMH based on its site of manifestation can help the radiologist when encountered with a finding that is diagnostic for EMH, and can help the radiologist suggest the need and plan appropriately for image-guided biopsy. PMID- 27377324 TI - [Spanish patients with central hypoventilation syndrome included in the European Registry. The 2015 data]. AB - INTRODUCTION: Congenital Central Hypoventilation Syndrome (CCHS) is a very rare genetic disease. In 2012 the European Central Hypoventilation Syndrome (EuCHS) Consortium created an online patient registry in order to improve care. AIM: To determine the characteristics and outcomes of Spanish patients with CCHS, and detect clinical areas for improvement. MATERIALS AND METHOD: An assessment was made on the data from Spanish patients in the European Registry, updated on December 2015. RESULTS: The Registry contained 38 patients, born between 1987 and 2013, in 18 hospitals. Thirteen (34.2%) were older than 18 years. Three patients had died. Genetic analysis identified PHOX2B mutations in 32 (86.5%) out of 37 patients assessed. The 20/25, 20/26 and 20/27 polyalanine repeat mutations (PARMs) represented 84.3% of all mutations. Longer PARMs had more, as well as more severe, autonomic dysfunctions. Eye diseases were present in 47%, with 16% having Hirschsprung disease, 13% with hypoglycaemia, and 5% with tumours. Thirty patients (79%) required ventilation from the neonatal period onwards, and 8 (21%) later on in life (late onset/presentation). Eight children (21%) were using mask ventilation at the first home discharge. Five of them were infants with neonatal onset, two of them, both having a severe mutation, were switched to tracheostomy after cardiorespiratory arrest at home. Approximately one-third (34.3%) of patients were de-cannulated and switched to mask ventilation at a mean age of 13.7 years. Educational reinforcement was required in 29.4% of children attending school. CONCLUSION: The implementation of the EuCHS Registry in Spain has identified some relevant issues for optimising healthcare, such as the importance of genetic study for diagnosis and assessment of severity, the high frequency of eye disease and educational reinforcement, as well as some limitations in ventilatory techniques. PMID- 27377326 TI - WITHDRAWN: Discovery of SHR1977: A highly potent and selective ROMK inhibitor. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 27377327 TI - Novel potent pyridoxine-based inhibitors of AChE and BChE, structural analogs of pyridostigmine, with improved in vivo safety profile. AB - We report a novel class of carbamate-type ChE inhibitors, structural analogs of pyridostigmine. A small library of congeneric pyridoxine-based compounds was designed, synthesized and evaluated for AChE and BChE enzymes inhibition in vitro. The most active compounds have potent enzyme inhibiting activity with IC50 values in the range of 0.46-2.1MUM (for AChE) and 0.59-8.1MUM (for BChE), with moderate selectivity for AChE comparable with that of pyridostigmine and neostigmine. Acute toxicity studies using mice models demonstrated excellent safety profile of the obtained compounds with LD50 in the range of 22-326mg/kg, while pyridostigmine and neostigmine are much more toxic (LD50 3.3 and 0.51mg/kg, respectively). The obtained results pave the way to design of novel potent and safe cholinesterase inhibitors for symptomatic treatment of neuromuscular disorders. PMID- 27377329 TI - Technical Comment: Response to Camacho. PMID- 27377330 TI - Image guidance in orthopaedics and traumatology: A historical perspective. AB - In this note we summarize the history of computer aided surgery in orthopaedics and traumatology from the end of the nineteenth century to currently observable future trends. We concentrate on the two major components of such systems, pre operative planning and intra-operative execution. The evolution of the necessary technological components, the numerous platforms and components offered commercially as well as their clinical use are surveyed. PMID- 27377328 TI - Quinoxaline-based inhibitors of Ebola and Marburg VP40 egress. AB - We prepared a series of quinoxalin-2-mercapto-acetyl-urea analogs and evaluated them for their ability to inhibit viral egress in our Marburg and Ebola VP40 VLP budding assays in HEK293T cells. We also evaluated selected compounds in our bimolecular complementation assay (BiMC) to detect and visualize a Marburg mVP40 Nedd4 interaction in live mammalian cells. Antiviral activity was assessed for selected compounds using a live recombinant vesicular stomatitis virus (VSV) (M40 virus) that expresses the EBOV VP40 PPxY L-domain. Finally selected compounds were evaluated in several ADME assays to have an early assessment of their drug properties. Our compounds had low nM potency in these assays (e.g., compounds 21, 24, 26, 39), and had good human liver microsome stability, as well as little or no inhibition of P450 3A4. PMID- 27377331 TI - (Hyper)-graphical models in biomedical image analysis. AB - Computational vision, visual computing and biomedical image analysis have made tremendous progress over the past two decades. This is mostly due the development of efficient learning and inference algorithms which allow better and richer modeling of image and visual understanding tasks. Hyper-graph representations are among the most prominent tools to address such perception through the casting of perception as a graph optimization problem. In this paper, we briefly introduce the importance of such representations, discuss their strength and limitations, provide appropriate strategies for their inference and present their application to address a variety of problems in biomedical image analysis. PMID- 27377332 TI - Statistical shape analysis: From landmarks to diffeomorphisms. AB - We offer a blazingly brief review of evolution of shape analysis methods in medical imaging. As the representations and the statistical models grew more sophisticated, the problem of shape analysis has been gradually redefined to accept images rather than binary segmentations as a starting point. This transformation enabled shape analysis to take its rightful place in the arsenal of tools for extracting and understanding patterns in large clinical image sets. We speculate on the future developments in shape analysis and potential applications that would bring this mathematically rich area to bear on clinical practice. PMID- 27377333 TI - LVAD patients' and surrogates' perspectives on SPIRIT-HF: An advance care planning discussion. AB - OBJECTIVES: To describe LVAD patients' and surrogates' experiences with, and perspectives on SPIRIT-HF, an advance care planning (ACP) intervention. BACKGROUND: ACP is important for patients with LVAD, yet little is known about their experiences or those of their surrogates who have participated in ACP discussions. METHODS: We used qualitative content analysis techniques to conduct a secondary analysis of 28 interviews with patients with LVAD (n = 14) and their surrogates (n = 14) who had participated in an RCT pilot study of SPIRIT-HF. RESULTS: Main themes from the data include: 1) sharing their HF stories was very beneficial; 2) participating in SPIRIT-HF led to greater peace of mind for patients and surrogates; 3) "one size does not fit all" when it comes to timing of ACP discussions. CONCLUSIONS: An understanding patient and surrogate perspectives may inform clinicians' approach to ACP discussions. PMID- 27377334 TI - The effect of reintubation on ventilator-associated pneumonia and mortality among mechanically ventilated patients with intubation: A systematic review and meta analysis. AB - OBJECTIVES: This meta-analysis summarized the risks that reintubation impose on ventilator-associated pneumonia (VAP) and mortality. BACKGROUND: Extubation failure increases the probability of poor clinical outcomes pertaining to mechanical ventilation. METHODS: Literature published during a 15-year period was retrieved from PubMed, Web of Knowledge databases, the Embase (Excerpa Medica database), and the Cochrane Library. Data involving reintubation, VAP, and mortality were extracted for a meta-analysis. RESULTS: Forty-one studies involving 29,923 patients were enrolled for the analysis. The summary odds ratio (OR) between VAP and reintubation was 7.57 (95% confidence interval [CI] = 3.63 15.81). The merged ORs for mortality in hospital and intensive care unit were 3.33 (95% CI = 2.02-5.49) and 7.50 (95% CI = 4.60-12.21), respectively. CONCLUSIONS: Reintubation can represent a threat to survival and increase the risk of VAP. The risk of mortality after reintubation differs between planned and unplanned extubation. Extubation failure is associated with a higher risk of VAP in the cardiac surgery population than in the general population. PMID- 27377335 TI - Adverse family experiences and obesity in children and adolescents in the United States. AB - While exposure to adverse family experiences (AFEs), subset of adverse childhood experiences (ACEs), has been associated with childhood obesity, less is known about the impact of exposures to each type of AFE. Using 2011-2012 National Survey of Children's Health data, we evaluated associations between exposure to individual AFEs and overweight/obesity status in children 10years or older, adjusting for socio-demographic factors. Caregivers reported their child's height, weight, and exposure to nine AFEs; body mass index (BMI) was classified by Center for Disease Control and Prevention's (CDC) guidelines. At Mayo Clinic, we calculated frequencies and weighted estimates of socio-demographic factors and AFEs. Unadjusted and adjusted weighted multinomial logistic regression models were employed to assess the independent associations of each AFE and the different AFE composite scores with BMI category. Exposure to two or more AFEs was independently associated with increased odds of overweight (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.13, 1.56) and obese (OR, 1.45; 95% CI, 1.21, 1.73) status after adjustment for age, household income, parents' education level, race and sex. Death of parent (OR, 1.59; 95% CI, 1.18, 2.15) and hardship due to family income (OR, 1.26; 95% CI, 1.06, 1.50) were independently associated with obesity status with adjustment for other AFEs and socio-demographic factors. Our results suggest that, in addition to cumulative exposure to AFEs, exposure to certain childhood experiences are more strongly associated with childhood obesity than others. Death of parent and hardship due to family income are individual AFEs, which are strongly predictive of obesity. PMID- 27377336 TI - Antidiabetic and antihyperlipidemic activities of Forsythia suspensa (Thunb.) Vahl (fruit) in streptozotocin-induced diabetes mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Forsythia suspense (Thunb.) Vahl, a well-known Chinese Materia Medica, has been traditionally used in traditional Chinese medicine for the treatment of diabetes and some other diseases, but the rational for the usage of this plant is unclear. The aim of this study was to investigate the therapeutic effect and potential mechanism of the fruit of F. suspensa using streptozotocin (STZ)-induced diabetic mice. MATERIALS AND METHODS: Crude methanol extract of F. suspense fruit was fractionated with different solvents and the ethyl acetate fraction (EAF) was selected for in vivo studies based on the in vitro alpha-amylase and HMG-CoA reductase (3-hydroxy-3-methyl glutaryl coenzyme A) inhibiting activities. For in vivo study, diabetes mellitus was induced in mice with STZ. Diabetic mice were orally administrated with 50, 100 and 200mg/kg body weight of EAF for 4 weeks. Mouse body weight, blood glucose, glucose tolerance, biochemical parameters and gene expression related to pancreas and liver function were analyzed after EAF administration. RESULTS: After 4 weeks of EAF intervention, a significant decrease in blood glucose, triglyceride, creatinine total cholesterol, acid phosphatase, alkaline phosphatase, aspartate transaminase, alanine transaminase, and hepatic lipid (triglycerides and cholesterol) content as well as a significant increase in body weight, insulin secretion and glucose tolerance was observed in EAF treated diabetic mice. qRT-PCR analysis revealed that EAF antagonized STZ-induced alteration of the expression of rate-limiting enzymes (glucokinase and phosphorenolpyruvate carboxykinase) in liver and insulin secretion related genes insulin-1, insulin-2 and duodenal homeobox factor-1 in pancreas. CONCLUSION: The ethyl acetate extract of Forsythia suspense (Thunb.) Vahl fruit has potency to develop an antihyperglycemic and antihyperlipidemic agent for the treatment of diabetes mellitus via modulation of oxidative stress, the hepatic glucose metabolism and pancreatic insulin secretion. PMID- 27377337 TI - The rhizome of Gastrodia elata Blume - An ethnopharmacological review. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodia elata Blume (Orchidaceae) is commonly called Tian ma in Chinese and mainly distributed in the mountainous areas of eastern Asia, such as China, Korea, Japan and India. It is an extensively used traditional Chinese herbal medicine in the clinical practice of traditional Chinese medicine, to treat headache, migraine, dizziness, epilepsy, infantile convulsion, tetany and so on. The present paper reviews the advancements in investigation of botany and ethnopharmacology, phytochemistry, pharmacology, toxicology and quality control of Gastrodia elata Blume. Finally, the possible tendency and perspective for future investigation of this plant are also put forward. MATERIALS AND METHODS: The information on Gastrodia elata Blume was collected via piles of resources including classic books about Chinese herbal medicine, and scientific databases including Pubmed, Google Scholar, ACS, Web of science, ScienceDirect databases, CNKI and others. Plant taxonomy was validated by the databases "The Plant List", and "Mansfeld's Encyclopedia". RESULTS: Over 81 compounds from this plant have been isolated and identified, phenolics and polysaccharides are generally considered as the characteristic and active constituents of Gastrodia elata Blume. Its active compounds possess wide-reaching biological activities, including sedative, hypnotic, antiepileptic, anticonvulsive, antianxietic, antidepressant, neuroprotective, antipsychotic, anti-vertigo, circulatory system modulating, anti-inflammationary, analgesic, antioxidative, memory-improving and antiaging, antivirus and antitumor effects. CONCLUSION: Despite the publication of various papers on Gastrodia elata Blume, there is still, however, the need for definitive research and clarification of other bioactive compounds using bioactivity-guided isolation strategies, and the possible mechanism of action as well as potential synergistic or antagonistic effects of multi-component mixtures derived from Gastrodia elata Blume need to be evaluated. It is also necessary and important to do more quality control and toxicological study on human subjects in order to maintain its efficacy stable in the body and validate its safety in clinical uses. In addition, more investigations on other parts of this plant beyond the tubers are needed. Further studies on Gastrodia elata Blume will lead to the development of new drugs and therapeutics for various diseases, and how to utilize it better should be paid more attention to. PMID- 27377338 TI - 1HNMR-based metabonomic study of sub-chronic hepatotoxicity induced by realgar. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Realgar has been used as a traditional Chinese medicine (TCM) for thousands of years. Recently, a number of realgar or realgar containing medicines poisoning cases have been reported. However, the toxicological mechanism of realgar has not been clearly clarified. In present study, the subchronic hepatotoxicity of realgar on mice was investigated using 1HNMR-based metabonomic approaches. MATERIALS AND METHODS: Twenty-eight male mice were divided into control group and low (0.15g/kg), middle (0.45g/kg), high (1.35g/kg) dosage realgar exposed groups. Their plasma and urine samples were used for NMR spectroscopic metabolic profiling. Principal component analysis (PCA) and pathway analysis were used to detect the hepatotoxic effects of realgar. Liver histopathological examination and plasma clinical chemistry analyses were also performed. RESULTS: Plasma clinical chemistry analyses showed increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein (TP), total cholesterol (TC) and choline esterase (CHE) in realgar-exposed mice indicating liver injury. The PCA score plots showed the metabolic profiles of realgar-exposed mice apparently separated from the controls. Obvious dose-dependent changes of metabolites in urine and plasma of realgar-exposed mice were observed. From the loading plots and boxplots results, the concentrations of VLDL/LDL, 3-HB, lactate, acetate, acetoacetate, creatine, glutamate, methionine, NAc, TMAO, alanine in plasma and pyruvate, succinate, 2-oxoglutarate, DMA, citrate, hippurate, glycine, taurine, phenylalanine, lactate in urine were significantly changed in realgar-exposed mice. The change trends of metabolites in urine and plasma from mice sub-chronic exposed to realgar are similar to those reported in rats acute exposed to realgar, which indicate the acute and sub-chronic toxic mechanism of realgar are same. The disturbed metabolic pathway include energy metabolism, amino acids metabolism and gut bacteria metabolism. CONCLUSIONS: The present work illustrated the NMR-based metabonomic approach can capture and probe the metabolic alterations induced by traditional Chinese medicine in the toxicological effects. PMID- 27377339 TI - Safety and bioactivity studies of Jasad Bhasma and its in-process intermediate in Swiss mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Bhasma, Ayurvedic medicinal preparations, are prepared using herbs and minerals on following long iterative procedures. However, industrially mercury and sulphur are more commonly used to prepare bhasma from its raw material. The end point of this iterative procedure is mainly judged by the traditional tests specifying physical appearance of the powders. They fail to give better idea about chemical nature of the material. Moreover, the differences in biological activity of final product verses intermediate are not addressed. AIM OF THE STUDY: To compare the physicochemical as well as biological properties of the Jasad bhasma and its in-process intermediate using modern science methods. MATERIALS AND METHODS: The Jasad bhasma and its in process intermediate are characterized for their physicochemical properties using electron microscopy, x-ray diffraction and CHNS(O) analysis. The biological effects of both the preparations are then studied. The bioaccumulation of zinc, effect on liver antioxidant status, liver and kidney function (by conventional tests as well as SPECT: Single Photon Emission Computed Tomography), effect on blood cells and effect on immune system are studied in mice model, Swiss albino. Since bhasma is given with an accompaniment (anupan), all the bioactivity studies were carried out by administering the preparation with and without Amala powder (Phyllanthus emblica L., fruit, dry powder) as anupan. RESULTS: The XRD results accompanied with Rietveld analysis indicate that the final bhasma is mainly oxide of zinc, whereas the intermediate is mainly sulphide of zinc. The animal studies show that the bhasma as well as its intermediate do not lead to any bioaccumulation of zinc in major organs, when administered with and without anupan. Both, bhasma and intermediate do not cause any deleterious effects on kidney and liver as indicated by blood biochemistry and SPECT studies. However, the intermediate perturbs antioxidant status more and affects the platelet turnover, in comparison with bhasma. On 28day treatment, the bhasma treated animals show prominence of TH1 mediated immune response whereas, intermediate treated animals show prominence of TH2 mediated immune response. CONCLUSION: A set of simple modern microscopy and diffraction techniques can affirmatively identify in-process intermediate from the final preparation. These can be used to decide the end point of long and iterative preparation methods in accordance with modern science practices. The differences in physicochemical properties of particles from the two preparations reflect in their different biological effects. Moreover, the bhasma affects several components of biological systems which again in-turn interact with each other, which emphasizes the need of multifaceted studies in this field. PMID- 27377341 TI - Historical versus contemporary medicinal plant uses in the US Virgin Islands. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Hidden in the documents of the dark past of the trans-Atlantic slavery are gems of ethnomedicinal observations, supported by herbarium specimens, which tell of the traditional medicine of a by-gone slave society in the Caribbean. In the context of the former Danish West Indies (now US Virgin Islands), we identify pre-1900 medicinal plants and their historical uses, and trace their status in the traditional medicine of St. Croix today (2014). By a combined historical and ethnobotanical approach we assess the scale of loss and preservation of traditional medicinal knowledge on St. Croix, and explore the drivers involved in the disappearance of knowledge in the oral tradition of medicine. MATERIALS AND METHODS: Names, uses and identities of 18th and 19th century medicinal plant uses in the Danish West Indies were derived from manuscripts and publications of Von Rohr (1757/58), Oldendorp (1777), West (1793), Benzon (1822), Riise (1853), Eggers (1876;1879) and Berg and Eggers (1888). The presence of the plant species in the pre-1900 Danish West Indies was confirmed by review of herbarium specimens in the University of Copenhagen Herbarium (C). The same species were collected on St. Croix in 2014 or their ecological status discussed with local specialists. Semi-structured interviews supported by photographs and specimens were conducted with six medicinal plant specialist on St. Croix, to document and compare contemporary names and uses of the historically used medicinal plants. RESULTS AND DISCUSSION: The historic ethnomedicinal sources revealed 102 medicinal uses of 64 plant species. Thirty eight (37%) of the pre-1900 medicinal uses were traced in interviews, while sixty four uses (63%) appear to be forgotten, discontinued or otherwise lost. Thirteen species appear to have entirely lost their status as medicinal plants on St. Croix, while 32 species (50%) have lost uses while retaining or gaining others. While 20% of the lost medicinal plant uses can be explained by biodiversity loss, and others likely have become obsolete due to advances in public health and scientific medicine, 33 of the 64 lost medicinal uses of non-rare species uses fall in the same categories as the preserved uses (fever, stomach, wound, laxative, pulmonary, intestinal, pain, anthelmintic, blood purifier, eye inflammation). We therefore argue that at least half of the known pre-1900 medicinal plant uses have become culturally extinct for other reasons than to biodiversity loss or modern obsoleteness. CONCLUSIONS: The present study utilized knowledge from an oral medicinal tradition, documented in the context of a colonial society. Without doubt, basis for further similar studies exists in the more or less accessible archives, herbaria and collections of former colonial powers. Such studies could directly benefit the descendants of the original intellectual property holders culturally and economically, or serve as stepping stones to integrate, or re-integrate, lost medicinal plant uses in both local and wider evidence-based contexts. PMID- 27377340 TI - Evidence of anti-inflammatory and antinociceptive activities of Plinia edulis leaf infusion. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Plinia edulis (Vell.) Sobral (Myrtaceae) is native and endemic to the Brazilian Atlantic Rainforest. Popularly known as "cambuca", it has been used in folk medicine for the treatment of stomach disorders, diabetes, bronchitis, inflammation and as tonic. Although there are numerous records concerning its popular use as analgesic and anti-inflammatory, scientific information regarding these pharmacological activities is limited. Therefore, the aim of this study was to characterize the anti-inflammatory and antinociceptive activity of P. edulis leaf infusion (AEPe) in mice. MATERIALS AND METHODS: The acetic acid-induced writhing response and mechanical nociceptive paw tests were used to evaluate the antinociceptive activity. Carrageenan-induced paw edema and lipopolysaccharide-induced peritonitis were used to investigate the anti-inflammatory activity. The substances in AEPe were identified by HPLC-MS analysis. RESULTS: At the test doses 30-300mg/kg p.o., AEPe has clearly exhibited anti-inflammatory effects, reducing carrageenan-induced paw edema and inhibiting leukocyte recruitment into the peritoneal cavity. The infusion has shown significant antinociceptive activity in both models of nociception. Gallic acid, myricitrin, guaijaverin, quercitrin, quercetin, corosolic acid, maslinic acid, oleanolic acid and ursolic acid were identified in AEPe. CONCLUSION: P. edulis infusion presented antinociceptive and anti-inflammatory activities in all experiments realized in this study, which could be related to the presence of triterpenoids and flavonoids. These results provide scientific support for the traditional use of this species in the management of pain and inflammation. PMID- 27377342 TI - Impact of removing point-of-sale tobacco displays: data from a New Zealand youth survey. AB - INTRODUCTION: The tobacco industry increasingly invests in point-of-sale (POS) marketing. In July 2012, New Zealand required the removal of POS tobacco displays concurrently with increased enforcement and penalties for selling tobacco to minors, and additional restrictions on tobacco sponsorship. We evaluated the impact of these measures using a before-after study. METHODS: We analysed data from annual surveys of more than 25 000 year 10 (14-15 years) students from 2007 and 2011 to 2014. Measures included prevalence of smoking-related behaviours and strength of association between visiting tobacco-retailing stores and smoking behaviours. RESULTS: Between 2011 and 2014, smoking experimentation (had smoked ever but smoked less than monthly currently) decreased from 23% in 2011 to 17% in 2014 (adjusted odds ratio (aOR) 0.73, 95% CI 0.69 to 0.78); current smoking (at least monthly) prevalence from 9% to 7% (aOR 0.71, 0.64 to 0.79) and initiation in the last year from 13% to 11% (aOR 0.91, 0.84 to 0.98). Attempted purchase of cigarettes in the past 30 days among smokers decreased from 30% in 2012 to 26% in 2013 (aOR 0.77, 0.63 to 0.91). Positive associations between frequency of visiting tobacco-retailing stores and smoking-related behaviours weakened post implementation. CONCLUSIONS: The introduction of a POS display ban and concurrent measures was followed by significant reductions in initiation, experimental and regular smoking, attempted purchase of cigarettes, and reduced association between visiting tobacco-retailing stores and smoking behaviours. The findings suggest that POS display bans are important components of strategies to reduce smoking initiation among youth and young people. PMID- 27377343 TI - Demographic ageing and the evolution of smoking-attributable mortality: the example of Germany. AB - OBJECTIVE: We sought to quantify the evolution of smoking-attributable mortality (SAM) in Germany and explore the impact of demographic ageing. METHODS: Smoking and mortality statistics from 1992 to 2013 were obtained from the German Statistical Office, from which SAM was calculated separately for each cause of death. The impact of demographic ageing was explored by comparing actual (crude) and age-standardised SAM. In order to estimate the impact of demographic ageing on future SAM, a forward projection until 2035 was modelled (assuming continuation of recent trends in smoking rates and constant cause-specific mortality rates). RESULTS: Total SAM only slightly declined from 139 000 cases in 1992 to 125 000 cases in 2013 (-10%), despite a decrease in age-adjusted SAM by 33%. Differences between actual and age-standardised SAM were particularly striking in men. While the age-standardised SAM in men decreased nearly by half, SAM remained more or less stable in women. The forward projection of SAM suggests that demographic ageing will lead to a further steady increase in SAM within the next two decades, for both, men and women. CONCLUSIONS: Especially in men, actual SAM hardly declined despite a sharp drop in age-standardised SAM, indicating that decreases were largely compensated by demographic ageing. The increasing number of deaths resulting from the ageing population will lead to a steady increase in SAM in the near future if no efforts are taken to curb smoking. PMID- 27377345 TI - Proinflammatory responses driven by non-gluten factors are masked when they appear associated to gliadins. AB - Cereal proteins are of clinical interest because of their cytotoxic and immunogenic features being associated to allergic processes and intestinal disorders. In addition to gliadins, there has been suggested an important role for non-gluten modulating factors (nGMF) on the onset of intestinal inflammatory processes. In this study, the amino acid sequences generated after a simulated human gastrointestinal (sGI) digestion of a commercial extract of gliadins (GEF) and the nGMF-enriched fraction (nGEF) obtained from them were characterized (nanoESI-qQTOF). These fractions were fed (20 days) to Wistar rats, sensitized with interferon (IFN)-gamma (1000 IU/rat) and further treated with indomethacin (2 mg/kg). The production of inflammatory mediators (ELISAs) and the expression (rt-qPCR) of innate biomarkers was monitored in duodenal tissue sections. There were also evaluated changes in defined leukocyte (flow cytometry) populations quantified in peripheral blood samples. Expected nGMF components, CM3 and 0.19, as well as toxic gliadin-derived peptides were generated after sGI digestion. Rats fed with the nGEF showed higher concentrations of IFNgamma, as well as expression levels of TLR-4 and the peroxisome proliferator activated receptor alpha in duodenal samples than those animals fed with GEF. Rats fed with GEF showed higher expression levels of the endocannabinoid receptor-1 and an increased CD4(+)CD3(+)Foxp3(+) cell population. The data points out significant different cytotoxic and immunogenic potential of the nGEF when administered independently of the GEF to which are commonly associated. However, proinflammatory responses to nGMF are masked when present associated to gliadins. PMID- 27377344 TI - Parallel processing of afferent olfactory sensory information. AB - KEY POINTS: The functional synaptic connectivity between olfactory receptor neurons and principal cells within the olfactory bulb is not well understood. One view suggests that mitral cells, the primary output neuron of the olfactory bulb, are solely activated by feedforward excitation. Using focal, single glomerular stimulation, we demonstrate that mitral cells receive direct, monosynaptic input from olfactory receptor neurons. Compared to external tufted cells, mitral cells have a prolonged afferent-evoked EPSC, which serves to amplify the synaptic input. The properties of presynaptic glutamate release from olfactory receptor neurons are similar between mitral and external tufted cells. Our data suggest that afferent input enters the olfactory bulb in a parallel fashion. ABSTRACT: Primary olfactory receptor neurons terminate in anatomically and functionally discrete cortical modules known as olfactory bulb glomeruli. The synaptic connectivity and postsynaptic responses of mitral and external tufted cells within the glomerulus may involve both direct and indirect components. For example, it has been suggested that sensory input to mitral cells is indirect through feedforward excitation from external tufted cells. We also observed feedforward excitation of mitral cells with weak stimulation of the olfactory nerve layer; however, focal stimulation of an axon bundle entering an individual glomerulus revealed that mitral cells receive monosynaptic afferent inputs. Although external tufted cells had a 4.1-fold larger peak EPSC amplitude, integration of the evoked currents showed that the synaptic charge was 5-fold larger in mitral cells, reflecting the prolonged response in mitral cells. Presynaptic afferents onto mitral and external tufted cells had similar quantal amplitude and release probability, suggesting that the larger peak EPSC in external tufted cells was the result of more synaptic contacts. The results of the present study indicate that the monosynaptic afferent input to mitral cells depends on the strength of odorant stimulation. The enhanced spiking that we observed in response to brief afferent input provides a mechanism for amplifying sensory information and contrasts with the transient response in external tufted cells. These parallel input paths may have discrete functions in processing olfactory sensory input. PMID- 27377346 TI - Factors regulating the substrate specificity of cytosolic phospholipase A2-alpha in vitro. AB - Cytosolic phospholipase A2 alpha (cPLA2alpha) plays a key role in signaling in mammalian cells by releasing arachidonic acid (AA) from glycerophospholipids (GPLs) but the factors determining the specificity of cPLA2alpha for AA containing GPLs are not well understood. Accordingly, we investigated those factors by determining the activity of human cPLA2alpha towards a multitude of GPL species present in micelles or bilayers. Studies on isomeric PC sets containing a saturated acyl chain of 6 to 24 carbons in the sn1 or sn2 position in micelles showed an abrupt decrease in hydrolysis when the length of the sn1 or sn2 chain exceeded 17 carbons suggesting that the acyl binding cavity on the enzyme is of the corresponding length. Notably, the saturated isomer pairs were hydrolyzed identically in micelles as well as in bilayers suggesting promiscuous binding of acyl chains to the active site of cPLA2alpha. Such promiscuous binding would explain the previous finding that cPLA2alpha has both PLA1 and PLA2 activities. Interestingly, increasing the length of either the sn1 or sn2 acyl chain inhibited the hydrolysis in bilayers far more than that in micelles suggesting that with micelles (loosely packed) substrate accommodation at the active site of cPLA2alpha is rate-limiting, while with bilayers (tightly packed) upward movement of the substrate from the bilayer (efflux) is the rate-limiting step. With the AA-containing PCs, the length of the saturated acyl chain also had a much stronger effect on hydrolysis in bilayers vs. micelles in agreement with this model. In contrast to saturated PCs, a marked isomer preference was observed for AA-containing PCs both in micelles and bilayers. In conclusion, these data significantly help to understand the mode of action and specificity of cPLA2alpha. PMID- 27377347 TI - Mitochondrial acyltransferases and glycerophospholipid metabolism. AB - Our understanding of the synthesis and remodeling of mitochondrial phospholipids remains incomplete. Two isoforms of glycerol-3-phosphate acyltransferase (GPAT1 and 2) and two isoforms of acylglycerol-3-phosphate acyltransferase (AGPAT4 and 5) are located on the outer mitochondrial membrane, suggesting that both lysophosphatidic acid and phosphatidic acid are synthesized in situ for de novo glycerolipid biosynthesis. However, it is believed that the phosphatidic acid substrate for cardiolipin and phosphatidylethanolamine biosynthesis is produced at the endoplasmic reticulum whereas the phosphatidic acid synthesized in the mitochondria must be transferred to the endoplasmic reticulum before it undergoes additional steps to form the mature phospholipids that are trafficked back to the mitochondria. It is unclear whether mitochondrial phospholipids are remodeled by mitochondrial acyltransferases or whether lysophospholipids must return to the endoplasmic reticulum or to the mitochondrial associated membrane for reesterification. In this review we will focus on the few glycerolipid acyltransferases that are known to be mitochondrial. This article is part of a Special Issue entitled: Lipids of Mitochondria edited by Guenther Daum. PMID- 27377348 TI - The effect of Nurse GraduaTeness on patient mortality: a cross-sectional survey (the NuGaT study). AB - AIM: To investigate the relationship between patient mortality and the educational preparation (graduateness) of the nurses who cared for them. BACKGROUND: There have been 18 studies over the last two decades examining the effect of nurses' educational qualifications on mortality. All but three have used mortality data aggregated at the hospital level that has been combined with surveys of nurses to estimate the level of graduateness in the population. Data collection and extraction generally has been done at different points in time. DESIGN: A retrospective, cross-sectional study. METHOD: Routine administrative patient data were extracted (May-August 2015). The primary outcome was all-cause patient mortality at discharge. We were able to identify the individual nurses who provided care during patients inpatient stay using an identification number. We were then able to calculate the 'graduateness' of the nursing care patients received by dividing the number of recorded episodes of care provided by baccalaureate prepared nurses with the total number of care episodes. RESULTS: After adjusting for confounding, we observed a significant association between patient mortality and nurse graduateness. Our observations suggest an optimum level of baccalaureate prepared nurses of approximately 70%. Above this level, there appears to be no additional decrease in mortality rates. CONCLUSION: This study represents an important methodological step forward over previous approaches. Our observations are generally consistent with existing literature and confirm the importance of baccalaureate nurse education. PMID- 27377349 TI - One-Step Assembly of Phytic Acid Metal Complexes for Superhydrophilic Coatings. AB - While of immense scientific interest, superhydrophilic surfaces are usually difficult to prepare, and preparation methods are typically substrate specific. Herein, a one-step coating method is described that can endow superhydrophilicity to a variety of substrates, both inorganic and organic, using the coordination complexes of natural phytic acid and Fe(III) ions. Coating deposition occurs in minutes, and coatings are ultrathin, colorless, and transparent. Superhydrophilicity is attributed, in part, to the high density of phosphonic acid groups. The ease, rapidness, and mildness of the assembly process, which is also cost-effective and environmental-friendly, points towards potential applications, such as self-cleaning, oil/water separation, antifogging. PMID- 27377351 TI - Prevalence of age-related hearing loss, including sex differences, in older adults in a large cohort study. AB - OBJECTIVES/HYPOTHESIS: To obtain actual status of age-related hearing loss in a general unscreened population of older Dutch adults and to investigate whether the prevalence or degree has changed over time. STUDY DESIGN: To investigate the prevalence and degree of hearing loss, we conducted a large prospective cohort study of older adults between February 2011 and July 2015. METHODS: Pure-tone air and bone-conduction thresholds were measured for 4,743 participants. Results were compared to previous cohort studies. RESULTS: As expected, hearing loss increased with age. We found a correlation of R2 = 0.317 for men and R2 = 0.354 for women (right ears). A prevalence of hearing loss greater than 35 dB hearing level the average of 0.5/1/2/4 kHz in the better ear, was found in 33% of the male and almost 29% of the female participants aged 65 years and older. Compared with previous studies, men had less hearing loss at the frequencies of 2 kHz and above. Hearing thresholds in women were significantly higher at 4 and 8 kHz. The difference in hearing loss between men and women is significantly less than in earlier studies. CONCLUSIONS: Our study confirms that hearing loss is highly prevalent in the general unscreened population of older adults. However, the difference in hearing between sexes was considerably less than previously reported. This is probably due to changing lifestyle and environmental circumstances, LEVEL OF EVIDENCE: 2b Laryngoscope, 127:725-730, 2017. PMID- 27377350 TI - Incorporating Geriatric Assessment into a Nephrology Clinic: Preliminary Data from Two Models of Care. AB - Older adults with advanced chronic kidney disease (CKD) experience functional impairment that can complicate CKD management. Failure to recognize functional impairment may put these individuals at risk of further functional decline, nursing home placement, and missed opportunities for timely goals-of-care conversations. Routine geriatric assessment could be a useful tool for identifying older adults with CKD who are at risk of functional decline and provide contextual information to guide clinical decision-making. Two innovative programs were implemented in the Veterans Health Administration that incorporate geriatric assessment into a nephrology visit. In one program, a geriatrician embedded in a nephrology clinic used standardized geriatric assessment tools with individuals with CKD aged 70 and older (Comprehensive Geriatric Assessment for CKD) (CGA-4-CKD). In the second program, a nephrology clinic used comprehensive appointments for individuals aged 75 and older to conduct geriatric assessments and CKD care (Renal Silver). Data on 68 veterans who had geriatric assessments through these programs between November 2013 and May 2015 are reported. In CGA-4 CKD, difficulty with one or more activities of daily living (ADLs), history of falls, and cognitive impairment were each found in 27.3% of participants. ADL difficulty was found in 65.7%, falls in 28.6%, and cognitive impairment in 51.6% of participants in Renal Silver. Geriatric assessment guided care processes in 45.4% (n = 15) of veterans in the CGA-4-CKD program and 37.1% (n = 13) of those in Renal Silver. Findings suggest there is a significant burden of functional impairment in older adults with CKD. Knowledge of this impairment is applicable to CKD management. PMID- 27377352 TI - Supporting grocery shopping for students with intellectual disability:a preliminary study. AB - PURPOSE: Decades of research exist supporting various types of self-operating prompting systems, including picture, audio and video to help students with disabilities acquire skills, especially to teach life skills. While many facets of life skills are important to target for instruction for secondary students with intellectual disability, one receiving declining attention is grocery shopping. METHOD: Using a single subject alternating treatment design with two high school students with intellectual disability, the authors analysed the impact of three self-operating prompts systems - picture, audio and video - on students' successful selection of grocery items, independence in completing the task (i.e., percent of steps not prompted), and task completion time. RESULTS: Results showed video prompting to be most successful prompting system for both students for selecting grocery items. However, independence and task completion time varied significantly for the students across the prompting systems. CONCLUSIONS: It is important to match the correct prompting system to individual students' skills, needs and preference, but also to balance efficiency - both for educators and students. Implications for Rehabilitation Video prompting is an effective instructional strategy, but must be considered in light of time and skill to create the video prompts as well as social stigmatization of use in natural community settings. It is important to match the correct prompting system to each student, but also to balance efficiency - both for educators and students. PMID- 27377354 TI - 3D Printed Micro Free-Flow Electrophoresis Device. AB - The cost, time, and restrictions on creative flexibility associated with current fabrication methods present significant challenges in the development and application of microfluidic devices. Additive manufacturing, also referred to as three-dimensional (3D) printing, provides many advantages over existing methods. With 3D printing, devices can be made in a cost-effective manner with the ability to rapidly prototype new designs. We have fabricated a micro free-flow electrophoresis (MUFFE) device using a low-cost, consumer-grade 3D printer. Test prints were performed to determine the minimum feature sizes that could be reproducibly produced using 3D printing fabrication. Microfluidic ridges could be fabricated with dimensions as small as 20 MUm high * 640 MUm wide. Minimum valley dimensions were 30 MUm wide * 130 MUm wide. An acetone vapor bath was used to smooth acrylonitrile-butadiene-styrene (ABS) surfaces and facilitate bonding of fully enclosed channels. The surfaces of the 3D-printed features were profiled and compared to a similar device fabricated in a glass substrate. Stable stream profiles were obtained in a 3D-printed MUFFE device. Separations of fluorescent dyes in the 3D-printed device and its glass counterpart were comparable. A MUFFE separation of myoglobin and cytochrome c was also demonstrated on a 3D-printed device. Limits of detection for rhodamine 110 were determined to be 2 and 0.3 nM for the 3D-printed and glass devices, respectively. PMID- 27377353 TI - Target margins in radiotherapy of prostate cancer. AB - We reviewed the literature on the use of margins in radiotherapy of patients with prostate cancer, focusing on different options for image guidance (IG) and technical issues. The search in PubMed database was limited to include studies that involved external beam radiotherapy of the intact prostate. Post prostatectomy studies, brachytherapy and particle therapy were excluded. Each article was characterized according to the IG strategy used: positioning on external marks using room lasers, bone anatomy and soft tissue match, usage of fiducial markers, electromagnetic tracking and adapted delivery. A lack of uniformity in margin selection among institutions was evident from the review. In general, introduction of pre- and in-treatment IG was associated with smaller planning target volume (PTV) margins, but there was a lack of definitive experimental/clinical studies providing robust information on selection of exact PTV values. In addition, there is a lack of comparative research regarding the cost-benefit ratio of the different strategies: insertion of fiducial markers or electromagnetic transponders facilitates prostate gland localization but at a price of invasive procedure; frequent pre-treatment imaging increases patient in room time, dose and labour; online plan adaptation should improve radiation delivery accuracy but requires fast and precise computation. Finally, optimal protocols for quality assurance procedures need to be established. PMID- 27377355 TI - Collagen Substrate Stiffness Anisotropy Affects Cellular Elongation, Nuclear Shape, and Stem Cell Fate toward Anisotropic Tissue Lineage. AB - Rigidity of substrates plays an important role in stem cell fate. Studies are commonly carried out on isotropically stiff substrate or substrates with unidirectional stiffness gradients. However, many native tissues are anisotropically stiff and it is unknown whether controlled presentation of stiff and compliant material axes on the same substrate governs cytoskeletal and nuclear morphology, as well as stem cell differentiation. In this study, electrocompacted collagen sheets are stretched to varying degrees to tune the stiffness anisotropy (SA) in the range of 1 to 8, resulting in stiff and compliant material axes orthogonal to each other. The cytoskeletal aspect ratio increased with increasing SA by about fourfold. Such elongation was absent on cellulose acetate replicas of aligned collagen surfaces indicating that the elongation was not driven by surface topography. Mesenchymal stem cells (MSCs) seeded on varying anisotropy sheets displayed a dose-dependent upregulation of tendon-related markers such as Mohawk and Scleraxis. After 21 d of culture, highly anisotropic sheets induced greater levels of production of type-I, type III collagen, and thrombospondin-4. Therefore, SA has direct effects on MSC differentiation. These findings may also have ramifications of stem cell fate on other anisotropically stiff tissues, such as skeletal/cardiac muscles, ligaments, and bone. PMID- 27377356 TI - Basal ganglia output reflects internally-specified movements. AB - How movements are selected is a fundamental question in systems neuroscience. While many studies have elucidated the sensorimotor transformations underlying stimulus-guided movements, less is known about how internal goals - critical drivers of goal-directed behavior - guide movements. The basal ganglia are known to bias movement selection according to value, one form of internal goal. Here, we examine whether other internal goals, in addition to value, also influence movements via the basal ganglia. We designed a novel task for mice that dissociated equally rewarded internally-specified and stimulus-guided movements, allowing us to test how each engaged the basal ganglia. We found that activity in the substantia nigra pars reticulata, a basal ganglia output, predictably differed preceding internally-specified and stimulus-guided movements. Incorporating these results into a simple model suggests that internally specified movements may be facilitated relative to stimulus-guided movements by basal ganglia processing. PMID- 27377357 TI - Bottom-up and top-down influences at untrained conditions determine perceptual learning specificity and transfer. AB - Perceptual learning is often orientation and location specific, which may indicate neuronal plasticity in early visual areas. However, learning specificity diminishes with additional exposure of the transfer orientation or location via irrelevant tasks, suggesting that the specificity is related to untrained conditions, likely because neurons representing untrained conditions are neither bottom-up stimulated nor top-down attended during training. To demonstrate these top-down and bottom-up contributions, we applied a "continuous flash suppression" technique to suppress the exposure stimulus into sub-consciousness, and with additional manipulations to achieve pure bottom-up stimulation or top-down attention with the transfer condition. We found that either bottom-up or top-down influences enabled significant transfer of orientation and Vernier discrimination learning. These results suggest that learning specificity may result from under activations of untrained visual neurons due to insufficient bottom-up stimulation and/or top-down attention during training. High-level perceptual learning thus may not functionally connect to these neurons for learning transfer. PMID- 27377358 TI - Polymeric black tea polyphenols (PBPs) inhibit benzo(a)pyrene and 4 (methylnitrosamino)-1-(3-pyridyl)-1- butanone-induced lung carcinogenesis potentially through down-regulation of p38 and Akt phosphorylation in A/J mice. AB - The aim of our study was to evaluate chemopreventive efficacy and possible mechanism of most abundant polyphenolic fraction in black tea, polymeric black tea polyphenols (PBPs), in experimental lung carcinogenesis model. Effect of 1.5% black tea derived PBPs on benzo(a)pyrene [B(a)P] and 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone (NNK) induced lung lesions were studied over 28 wks. Chemopreventive efficacy was studied using decrease in tumor incidence and/or multiplicity and/or delay in the latency period in A/J mice. Histopathological analysis of lung was carried out post-carcinogen treatment weeks to analyze the microscopic lung lesions. Inflammation, cell proliferation, and apoptosis markers along with signaling kinases like p38, Akt, and their phosphorylated forms were studied using immunoblotting and immunohistochemistry at 4th, 10th, and 18th wk post-carcinogen treatment. Administration of PBPs throughout the treatment period significantly decreased the multiplicity of surface tumors as well as microscopic lung lesions, including adenomas. Although tumor incidence and latency period remains unaffected, histopathological evaluation of lung at 6, 10, and 18 wks post- carcinogen treatment period showed decrease in tumor multiplicity which was also correlated with different molecular markers. Anti- inflammatory action of PBPs was demonstrated by reduced Cox-2 expression. PBPs down-regulated the B(a)P and NNK-induced cell proliferation (diminished PCNA expression, proliferation index, and Bcl-2 expression) and enhanced apoptosis (increased Bax expression and apoptotic index) potentially through phosphorylation of p38 and Akt. PBPs, most abundant polyphenolic component in the black tea, have chemopreventive effect through inhibition of inflammation, cellular proliferation, and induction of apoptosis possibly via modulation of signaling kinases. (c) 2016 Wiley Periodicals, Inc. PMID- 27377359 TI - Medication safety in the home care setting: Development and piloting of a Critical Incident Reporting System AB - Background: While drug-related problems are among the most frequent adverse events in health care, little is known about their type and prevalence in home care in the current literature. The use of a Critical Incident Reporting System (CIRS), known as an economic and efficient tool to record medication errors for subsequent analysis, is widely implemented in inpatient care, but less established in ambulatory care. Recommendations on a possible format are scarce. A manual CIRS was developed based on the literature and subsequently piloted and implemented in a Swiss home care organization. Aim: The aim of this work was to implement a critical incident reporting system specifically for medication safety in home care. Results: The final CIRS form was well accepted among staff. Requiring limited resources, it allowed preliminary identification and trending of medication errors in home care. The most frequent error reports addressed medication preparation at the patients' home, encompassing the following errors: omission (30 %), wrong dose (17.5 %) and wrong time (15 %). The most frequent underlying causes were related to working conditions (37.9 %), lacking attention (68.2 %), time pressure (22.7 %) and interruptions by patients (9.1 %). Conclusions: A manual CIRS allowed efficient data collection and subsequent analysis of medication errors in order to plan future interventions for improvement of medication safety. The development of an electronic CIRS would allow a reduction of the expenditure of time regarding data collection and analysis. In addition, it would favour the development of a national CIRS network among home care institutions. PMID- 27377360 TI - ? PMID- 27377361 TI - Does general anesthesia have a clinical impact on intraocular pressure in children? AB - BACKGROUND: Reliable measurement of intraocular pressure (IOP) is crucial in pediatric patients with suspected glaucoma. General anesthesia (GA) is usually needed in infants to allow a thorough examination. However, anesthesia itself may influence IOP, depending on the type used and the depth of sedation. The purpose of this study was to evaluate the normal distribution of IOP during GA in healthy children and to analyze differences in IOP relative to the anesthetics used and the measurement time point. METHODS: Approval for this observational study was received from the local institutional review boards and written informed consent was obtained from the children's parents. A total of 100 pediatric patients with no history of glaucoma scheduled for nonintraocular surgery underwent general anesthesia, induced with sevoflurane (s) or propofol (p) and maintained with either sevoflurane with remifentanil (S) or propofol with remifentanil (P). The patients were grouped to one of four subgroups (sS, sP, pP, pS) depending on the anesthetics used during induction and maintenance. Hemodynamic parameters and IOP were measured in both eyes at four defined time points: before anesthesia induction (M1); in apnea immediately after induction and before insertion of a laryngeal mask airway (M2); in deep anesthesia during mechanical ventilation (M3); and after extubation (M4), using a handheld Perkins applanation tonometer. Differences in IOP in both eyes during the measurement periods were analyzed using multivariate repeated-measures analysis of variance and Tukey-HSD as a posthoc test with statistical significance set at P < 0.05. Pearson correlation coefficient was used to investigate further relationships between heart rate, systolic blood pressure, and IOP. RESULTS: General anesthesia reduced IOP significantly. The mean IOP was normally distributed, with a mean of 7.4 +/- 2.89 mmHg at M1. It decreased significantly to a minimum of 5.6 +/- 3.04 mmHg (P < 0.01) at M2 and increased significantly to 7.2 +/- 2.51 mmHg (P < 0.01) at M3 and again to 8.4 +/- 3.72 mmHg (P = 0.03) at M4. All four subgroups (sS, sP, pP, pS) showed comparable decreases in IOP between M1 and M2. During deep anesthesia (M3) and during reversal (M4), the IOP increased again in all groups. During reversal (M4), however, the sS group had a significantly lower IOP than the pP group (P = 0.001) and sP group (P = 0.02). There were no correlations between changes in IOP and gender, age, or type of surgery. CONCLUSIONS: Sevoflurane and propofol, both in combination with remifentanil, significantly lower IOP in children. Individual IOP levels rise and fall during anesthesia, depending on the time point of measurement. The lowest IOP can be measured immediately after induction of anesthesia. This needs to be taken into account when measuring IOP in children. PMID- 27377362 TI - Polyimide-coated magnetic nanoparticles as a sorbent in the solid-phase extraction of polycyclic aromatic hydrocarbons in seawater samples. AB - Magnetic polyimide poly(4,4'-oxydiphenylene-pyromellitimide) nanoparticles were successfully synthesized and developed for the solid-phase extraction of polycyclic aromatic hydrocarbons in seawater samples. The aromatic rings of polyimide coating provided a good adsorption capacity (28.3-42.5 mg/g) for polycyclic aromatic hydrocarbons because of the pi-pi stacking interaction. The developed method was used as a simple, fast, and efficient extraction and preconcentration technique for the trace analysis of polycyclic aromatic hydrocarbons. The high chemical, physical and thermal stability, excellent reusability, and good magnetic properties are the merits of the sorbent. High preconcentration factors (41-63) were obtained. The sorbent was also characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray spectrometry, transmission electron microscopy, and vibrating sample magnetometry. After optimizing several appropriate extraction parameters, the results indicated that the extraction recoveries of polycyclic aromatic hydrocarbons were in the range of 61.6-94.7%, with relative standard deviations between 2.9 and 5.4%, the calibration graph was linear in the concentration range of 1-100 MUg/L (r > 0.9991) with limit of detection in the range of 0.15-0.19 MUg/L (n = 3). Seawater samples were analyzed as real samples and good recoveries (68.5-99.5%) were obtained at different spiked values. PMID- 27377363 TI - MoYcp4 is required for growth, conidiogenesis and pathogenicity in Magnaporthe oryzae. AB - The transcription factor MoAP1 has been shown previously to be required for pathogenicity in Magnaporthe oryzae via mediation of the oxidative stress response. In the serial analysis gene expression database, it was found that expression of MoYcp4, a homologue of the Saccharomyces cerevisiae flavodoxin-like protein ScYcp4, was affected by MoAP1. Transcriptional analysis demonstrated that MoYCP4 was significantly up-regulated during conidiation, appressorium formation and infection. The growth rate of a DeltaMoycp4 mutant was reduced slightly, but conidial production was increased significantly (more than 10-fold), compared with the wild-type strain. Although the rate of appressorium formation was unaffected, the appressorial turgor was abnormal and the ability to infect rice and barley was reduced, resulting in decreased pathogenicity. In summary, MoYcp4, a target of MoAP1, is involved in the growth, conidiogenesis and pathogenicity of M. oryzae. Our studies provide a comprehensive analysis of flavodoxin-like proteins and will aid in the study of pathogen-related molecular mechanisms. PMID- 27377364 TI - Fracture of the clavicle and second rib: an indirect injury from tricep dips. AB - Due to the recent rise in the interest in strength training, an increment in the number of lesions is expected, whether of the tendons, muscles, or bones. We describe a case of fracture involving the middle third of the clavicle and the second rib in a low-demand weightlifter. The fractures occurred suddenly while performing a triceps dips exercise, and the patient had no previous symptoms. He was treated conservatively and was able to return to sports six months later. To our knowledge, this is the first study describing the association of these fractures triggered by a single event of muscle contraction. PMID- 27377365 TI - Cysteine redox proteomics of the hemoglobin-depleted cytosolic fraction of stored red blood cells. AB - PURPOSE: Erythrocyte concentrates (ECs) represent the most transfused labile blood products. They are stored at 4 degrees C in additive solutions for up to 56 days. Protein oxidation is a marker of oxidative stress and cysteine residues, whose oxidations are required for physiological cell functions, are highly prone to such modification. EXPERIMENTAL DESIGN: Five ECs from independent donations were followed. Soluble protein extracts were prepared at days 6, 27, and 41, and cysteines were alkylated, reduced, and labeled with infrared dyes. Samples were mixed two by two (day 6 as reference) and analyzed by 2D-DIGE. Detection of labeled cysteines allows quantitative comparison of oxidative status. Spots of interest were analyzed by proteomics. RESULTS: Thirty-two spots containing 43 proteins were classified as increasing, decreasing, or exhibiting a peak of expression during storage. Proteins having catalytic and antioxidant activities were particularly affected during storage, for example, peroxiredoxin-1 and DJ-1 were reversibly oxidized and catalase was irreversibly oxidized. These proteins could be used to evaluate different storage strategies to maintain proper protein function during the overall storage period. CONCLUSIONS AND CLINICAL RELEVANCE: This redox-DIGE approach brings new quantitative data on oxidized proteins in stored red blood cells. As previously reported on carbonylation, the oxidative damages differently affect protein functions. PMID- 27377366 TI - Longitudinal latent variable models given incompletely observed biomarkers and covariates. AB - In this paper, we analyze a two-level latent variable model for longitudinal data from the National Growth and Health Study where surrogate outcomes or biomarkers and covariates are subject to missingness at any of the levels. A conventional method for efficient handling of missing data is to re-express the desired model as a joint distribution of variables, including the biomarkers, that are subject to missingness conditional on all of the covariates that are completely observed, and estimate the joint model by maximum likelihood, which is then transformed to the desired model. The joint model, however, identifies more parameters than desired, in general. We show that the over-identified joint model produces biased estimation of the latent variable model and describe how to impose constraints on the joint model so that it has a one-to-one correspondence with the desired model for unbiased estimation. The constrained joint model handles missing data efficiently under the assumption of ignorable missing data and is estimated by a modified application of the expectation-maximization algorithm. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27377367 TI - A novel bis(pinacolato)diboron-mediated N-O bond deoxygenative route to C6 benzotriazolyl purine nucleoside derivatives. AB - Reaction of amide bonds in t-butyldimethylsilyl-protected inosine, 2' deoxyinosine, guanosine, 2'-deoxyguanosine, and 2-phenylinosine with commercially available peptide-coupling agents (benzotriazol-1H yloxy)tris(dimethylaminophosphonium) hexafluorophosphate (BOP), (6-chloro benzotriazol-1H-yloxy)trispyrrolidinophosphonium hexafluorophosphate (PyClocK), and (7-azabenzotriazol-1H-yloxy)trispyrrolidinophosphonium hexafluorophospate (PyAOP) gave the corresponding O(6)-(benzotriazol-1-yl) nucleoside analogues containing a C-O-N bond. Upon exposure to bis(pinacolato)diboron and base, the O(6)-(benzotriazol-1-yl) and O(6)-(6-chlorobenzotriazol-1-yl) purine nucleoside derivatives obtained from BOP and PyClocK, respectively, underwent N-O bond reduction and C-N bond formation, leading to the corresponding C6 benzotriazolyl purine nucleoside analogues. In contrast, the 7-azabenzotriazolyloxy purine nucleoside derivatives did not undergo efficient deoxygenation, but gave unsymmetrical nucleoside dimers instead. This is consistent with a prior report on the slow reduction of 1-hydroxy-1H-4-aza and 1-hydroxy-1H-7-azabenzotriazoles. Because of the limited number of commercial benzotriazole-based peptide coupling agents, and to show the applicability of the method when such coupling agents are unavailable, 1-hydroxy-1H-5,6-dichlorobenzotriazole was synthesized. Using this compound, silyl-protected inosine and 2'-deoxyinosine were converted to the O(6) (5,6-dichlorobenzotriazol-1-yl) derivatives via in situ amide activation with PyBroP. The O(6)-(5,6-dichlorobenzotriazol-1-yl) purine nucleosides so obtained also underwent smooth reduction to afford the corresponding C6 5,6 dichlorobenzotriazolyl purine nucleoside derivatives. A total of 13 examples were studied with successful reactions occurring in 11 cases (the azabenzotriazole derivatives, mentioned above, being the only unreactive entities). To understand whether these reactions are intra or intermolecular processes, a crossover experiment was conducted. The results of this experiment as well as those from reactions conducted in the absence of bis(pinacolato)diboron and in the presence of water indicate that detachment of the benzotriazoloxy group from the nucleoside likely occurs, followed by reduction, and reattachment of the ensuing benzotriazole, leading to products. PMID- 27377369 TI - Dual-Shell Fluorescent Nanoparticles for Self-Monitoring of pH-Responsive Molecule-Releasing in a Visualized Way. AB - The rational design and controlled synthesis of a smart device with flexibly tailored response ability is all along desirable for bioapplication but long remains a considerable challenge. Here, a pH-stimulated valve system with a visualized "on-off" mode is constructed through a dual-shell fluorescence resonance energy transfer (FRET) strategy. The dual shells refer to carbon dots and fluorescent molecules embedded polymethacrylic acid (F-PMAA) layers successively coating around a SiO2 core (ca. 120 nm), which play the roles as energy donor and acceptor, respectively. The total thickness of the dual-shell in the solid composite is ca. 10 nm. The priorities of this dual-shell FRET nanovalve stem from three facts: (1) the thin shell allows the formation of efficient FRET system without chemical bonding between energy donor and acceptor; (2) the maximum emission wavelength of CD layer is tunable in the range of 400 600 nm, thus providing a flexible energy donor for a wide variety of energy acceptors; (3) the outer F-PMAA shell with a pH-sensitive swelling-shrinking (on off) behavior functions as a valve for regulating the FRET process. As such, a sensitive and stable pH ratiometric sensor with a working pH range of 3-6 has been built by simply encapsulating pH-responsive fluorescein isothiocyanate (FITC) into PMAA; a pH-dependent swelling-shrinking shuttle carrier with a finely controllable molecule-release behavior has been further fabricated using rhodamine B isothiocyanate (RBITC) as the energy donor and model guest molecule. Significantly, the controlled releasing process is visually self-monitorable. PMID- 27377368 TI - The reemergence of long-term potentiation in aged Alzheimer's disease mouse model. AB - Mouse models of Alzheimer's disease (AD) have been developed to study the pathophysiology of amyloid beta protein (Abeta) toxicity, which is thought to cause severe clinical symptoms such as memory impairment in AD patients. However, inconsistencies exist between studies using these animal models, specifically in terms of the effects on synaptic plasticity, a major cellular model of learning and memory. Whereas some studies find impairments in plasticity in these models, others do not. We show that long-term potentiation (LTP), in the CA1 region of hippocampal slices from this mouse, is impared at Tg2576 adult 6-7 months old. However, LTP is inducible again in slices taken from Tg2576 aged 14-19 months old. In the aged Tg2576, we found that the percentage of parvalbumin (PV) expressing interneurons in hippocampal CA1-3 region is significantly decreased, and LTP inhibition or reversal mediated by NRG1/ErbB signaling, which requires ErbB4 receptors in PV interneurons, is impaired. Inhibition of ErbB receptor kinase in adult Tg2576 restores LTP but impairs depotentiation as shown in aged Tg2576. Our study suggests that hippocampal LTP reemerges in aged Tg2576. However, this reemerged LTP is an insuppressible form due to impaired NRG1/ErbB signaling, possibly through the loss of PV interneurons. PMID- 27377370 TI - Accuracy of Latarjet graft and screw position after using novel drill guide. AB - PURPOSE: For the success of Latarjet procedure a correct graft positioning is mandatory. Furthermore, the correct screw placement is important to avoid cartilage damage and soft tissue irritation. Due to a cadaveric experimental study, the accuracy of graft and screw positioning utilizing a novel drill guide for a minimal-invasive Latarjet procedure was analyzed. METHODS: Five human fresh frozen shoulder specimens have been treated in accordance with the Congruent-Arc Latarjet technique using the glenoid bone loss set (Arthrex, Naples, FL, USA) with 3.75 mm cannulated screws throughout a 5 cm skin incision without detachment of the scapularis tendon. All procedures were performed by one single, experienced shoulder surgeon. The accuracy of graft and screw positioning was assessed due to a CT scan. RESULTS: A noticeable learning curve was noted during the study period as the first surgery took 45 min and the last 33 min. All grafts were correctly positioned with regard to the articular line of the glenoid surface. Impingement with the maximum head circumference was not encountered. The screw positions did not affect the suprascapular nerve. A damage of the graft was not noticed. CONCLUSIONS: The authors can recommend the usage of the new drill guide tested in this study. It seems to be beneficial in the Latarjet procedure and may ease correct graft positioning and prevent screw misplacement. Compared to fully arthroscopically performed Latarjet procedures it provides much steeper learning curve and seems technically easier and quicker to handle. PMID- 27377371 TI - Bowel preparation prior to percutaneous ilio-sacral screw insertion: is it necessary? AB - PURPOSE: The aim of this study was to compare the outcomes of ilio-sacral (IS) screw fixation with and without the use of bowel preparation, in terms of obtaining adequate visualisation, malpositioning of screw requiring revision surgery and neurovascular injury. METHODS: A retrospective case control study was performed. We reviewed 74 consecutive cases of IS screw fixation performed at our institution within the last 5 years. We included all patients who had undergone percutaneous IS screw fixation. Two groups, one consisting of patients who underwent bowel preparation prior to surgery (Group 1) and one consisting of patients who had no bowel preparation (Group 2), were compared in terms of the above outcomes. There were 37 patients in each group. The mean age in Group 1 was 41 years (17-63) and in Group 2 was 47 years (12-89). RESULTS: In Group 1 there were two procedures abandoned due to poor visualisation. In Group 2 there were no cases abandoned for poor visualisation. There were two nerve injuries in Group 1 and no nerve injuries in Group 2. Revision surgery was performed in four patients in Group 1-for malposition, persistent buttock pain, sciatic nerve palsy and inadequate fixation while one revision performed in Group 2 for persistent buttock pain. CONCLUSION: Based on these results, we conclude that bowel preparation is not necessary to obtain adequate visualisation for safe and accurate percutaneous IS screw insertion. In fact, in Group 1 two procedures were abandoned and there was higher incidence of complications. Therefore, it would appear that this treatment arm should be abandoned all together. Further studies to prove it conclusively and explain the reasons are required. PMID- 27377372 TI - Well-defined, persistent, chiral phthalocyanine nanoclusters via G-quadruplex assembly. AB - Octameric near-IR dye nanoclusters are produced by complexation of potassium cations with a phthalocyanine-guanosine conjugate. The combination of hydrogen bonding, K(+) coordination, pi-pi stacking and steric interactions between the chiral side groups is responsible for defining a specific helical chromophore arrangement in the clusters, which display high stability and maintain their supramolecular identity onto substrates. PMID- 27377373 TI - Plasma total antioxidant capacity and peroxidation biomarkers in psoriasis. AB - Systemic biomarkers of oxidative stress can be relevant for assessment of psoriasis severity, for prediction of the outcome of therapy and of the development of comorbidities. In this review we aimed to evaluate the relationship between plasma total antioxidant capacity (TAC) and peroxidation biomarkers, as well as their association with dyslipidemia and systemic inflammation in psoriasis. The review of 59 case-control comparisons (from 41 studies) and 17 interventions (from 13 studies) suggests that peroxidation markers are more sensitive than TAC in the evaluation of oxidative stress in psoriasis. Although few studies investigated the effect of treatment on oxidative stress, it seems that biological drugs could be the better choice in the treatment of psoriasis. However, considering the limitations of TAC and plasma peroxidation markers, this review suggests that new methods should be developed in order to evaluate systemic oxidative stress in psoriasis. PMID- 27377374 TI - Seroprevalence of Orthopoxvirus in rural Brazil: insights into anti-OPV immunity status and its implications for emergent zoonotic OPV. AB - BACKGROUND: Bovine vaccinia (BV) is a zoonosis caused by Vaccinia virus, a virus from Orthopoxvirus genus (OPV) that affects mainly cattle herds and humans in rural areas in Brazil. Because most studies have focused on outbreaks situations, data on BV epidemiology is limited. A cross sectional study in Brazilian rural areas during 2012-2013 was conducted to determine the neutralizing antibodies seroprevalence and risk factors for BV. METHODS: A structured questionnaire was applied to elicit demographics data and farming practices considered risk factors for BV exposure. Neutralizing anti-OPV antibodies were investigated using plaque reduction neutralization test. The neutralizing antibodies prevalence rates were calculated and the risk factor analysis was performed using multivariate logistic regression. RESULTS: Two hundred and forty participants were enrolled in this study with a prevalence of neutralizing antibodies of 30.8 % (95 % confidence interval [CI], 25.3-36.9). In multivariate analysis, age > 35 years (Odds Ratio [OR] = 18.2; CI 95 % = 7.7 - 43.2) and previous outbreak in property (OR = 3.9; C I95 % = 1.2 - 12.6) were independently associated with anti-OPV neutralizing antibodies. CONCLUSIONS: In this study, anti-OPV protective immunity (neutralizing antibody titers) was assessed in an endemic BV Brazilian rural area. Our findings indicate that epidemiological surveillance is required and should be applied by public health authorities to create interventions and/or prevention strategies to avoid viral spread causing future outbreaks among individuals who are under risk of infection. PMID- 27377375 TI - CD80 down-regulation is associated to aberrant DNA methylation in non inflammatory colon carcinogenesis. AB - BACKGROUND: The lack of positive costimulatory molecules represents one of the mechanisms by which tumor cells evade immune surveillance. Promoter hypermethylation plays a major role in cancer development through transcriptional silencing of critical genes. The aim of this study was to examine the expression of the costimulatory molecule CD80 in relationship with genomic methylation in non-inflammatory colon carcinogenesis. METHODS: Colonic mucosal samples were collected from healthy subjects (n = 30) and from dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b and CD80 mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation specific PCR. CD80 expression was assessed in HT29, HCT-15 and LoVo cell lines after treatment with the DNA-methyltransferase inhibitor 5-Aza-2'-deoxycytidine. RESULTS: CD80 mRNA levels were significantly lower in the non-inflammatory dysplastic colonic mucosa of patients with one or more methylated genes and inversely correlated with patients' methylation scores (tau = -0.41, p = 0.05 and tau = -0.37, p = 0.05, respectively). Treatment with 5-Aza-2'-deoxycytidine significantly increased CD80 expression both in terms of the level of CD80 mRNA (p = 0.007) and of CD80+ cells (p = 0.003). CONCLUSIONS: These results indicate that the failure of immune surveillance mechanisms in non-inflammatory colon carcinogenesis may be linked to genomic methylation directly or indirectly affecting CD80 expression. PMID- 27377377 TI - Comparative Efficacy of Selected Dust Insecticides for Controlling Cimex lectularius (Hemiptera: Cimicidae). AB - Bed bugs, Cimex lectularius L., are one of the most difficult urban pests to control. Pest management professionals rely heavily on insecticide sprays and dusts to control bed bugs. Dust formulations are considered to provide longer residual control than sprays. However, there are no scientific data available on the comparative efficacy of the commonly used insecticide dusts. We evaluated the efficacy of eight insecticide dust products using three exposure methods: 1) brief exposure-bed bugs crossed a 2.54-cm-wide dust-treated band, 2) forced exposure-bed bugs were continuously exposed to a dust-treated substrate, and 3) choice exposure-bed bugs were given a choice to stay on either dust-treated or untreated substrate. The brief exposure method was the most sensitive in detecting the differences among the insecticides. Only CimeXa (silica gel) dust caused 100% mortality from all three exposure methods. Other tested dusts (1% cyfluthrin, 0.05% deltamethrin, 0.075% zeta-cypermethrin + 0.15% piperonyl butoxide, 1% pyrethrins, 1% 2-phenethyl propionate + 0.4% pyrethrin, 0.25% dinotefuran + 95% diatomaceous earth, 100% diatomaceous earth) caused <=65% mortality in a brief exposure assay. We also evaluated the horizontal transfer effect of the silica gel dust. Silica gel dust-exposed bed bugs transferred the dust horizontally to unexposed bed bugs resulting in 100% mortality at 4:6 donor: recipient ratio and 88.0 +/- 5.0% mortality at 1:5 donor: recipient ratio. The results suggest silica gel is the most promising insecticide dust for controlling C. lectularius. PMID- 27377376 TI - Adult attention-deficit/hyperactivity disorder and nicotine withdrawal: a qualitative study of patient perceptions. AB - BACKGROUND: Nicotine use has been reported to ameliorate symptoms of Attention Deficit/Hyperactivity Disorder (ADHD). Furthermore, adults with ADHD have a relatively high prevalence of cigarette smoking and greater difficulty abstaining from smoking. Overall, though, there is scant literature investigating the beliefs, perceptions and experiences of smokers with ADHD regarding smoking cessation and withdrawal. METHODS: Our participants (n = 20) fulfilling criteria for ADHD and a past or current dependence from nicotine were recruited from the in- and outpatient clinic of the Zurich University Psychiatric Hospital and the Psychiatric Services Aargau (Switzerland). We conducted in-depth interviews to explore their motivations to quit, past experiences with and expectations about quitting using a purposeful sampling plan. The sample was selected to provide diversity in relation to level of nicotine dependence, participation in a smoking cessation program, gender, age, martial status and social class. Mayring's qualitative content analysis approach was used to evaluate findings. RESULTS: Adult smokers with ADHD had made several attempts to quit, experienced intense withdrawal symptoms, and relapsed early and often. They also often perceived a worsening of ADHD symptoms with nicotine abstinence. We identified three motives to quit smoking: 1) health concerns, 2) the feeling of being addicted, and 3) social factors. Most participants favored a smoking cessation program specifically designed for individuals with ADHD because they thought ADHD complicated their nicotine withdrawal and that an ADHD-specific smoking cessation program should address specific symptoms of this disorder. CONCLUSIONS: Since treatment initiation and adherence associate closely with perception, we hope these findings will result in better cessation interventions for the vulnerable subgroup of smokers with ADHD. PMID- 27377378 TI - Annual Fluctuations of Early Immigrant Populations of Sogatella furcifera (Hemiptera: Delphacidae) in Jiangxi Province, China. AB - The white-backed planthopper, Sogatella furcifera (Horvath), is a destructive migratory pest in east and southeast Asia. Huge populations stemming from annual migrations by this insect have caused a series of devastating losses to rice production. There have been numerous early immigrations in five of the past 10 yr but few early immigrations in the others. The annual fluctuation in early immigration is evident, but the mechanism behind these annual fluctuations is unclear. This research aimed to determine the underlying causes for the annual fluctuations in early immigration. We used trajectory analysis to explore the source areas and investigated the meteorological conditions to determine the reason for the annual fluctuations. The results showed that 1) the source areas of S. furcifera are mainly located west of Guangdong and east of Guangxi; 2) the annual fluctuations of the immigrant population size is significantly correlated with the frequency of prevailing winds; and 3) early immigration is influenced by both winter and spring temperatures in the south central Indochina peninsula. These results indicated that an allopatric prediction and sustainable management of rice planthoppers would be difficult to implement within one country. International cooperation and information exchange about this pest between China and other countries in Southeast Asia should be implemented. PMID- 27377379 TI - Neutron and X-ray single-crystal diffraction from protein microcrystals via magnetically oriented microcrystal arrays in gels. AB - Protein microcrystals magnetically aligned in D2O hydrogels were subjected to neutron diffraction measurements, and reflections were observed for the first time to a resolution of 3.4 A from lysozyme microcrystals (~10 * 10 * 50 um). This result demonstrated the possibility that magnetically oriented microcrystals consolidated in D2O gels may provide a promising means to obtain single-crystal neutron diffraction from proteins that do not crystallize at the sizes required for neutron diffraction structure determination. In addition, lysozyme microcrystals aligned in H2O hydrogels allowed structure determination at a resolution of 1.76 A at room temperature by X-ray diffraction. The use of gels has advantages since the microcrystals are measured under hydrated conditions. PMID- 27377380 TI - Ab initio phasing by molecular averaging in real space with new criteria: application to structure determination of a betanodavirus. AB - Molecular averaging, including noncrystallographic symmetry (NCS) averaging, is a powerful method for ab initio phase determination and phase improvement. Applications of the cross-crystal averaging (CCA) method have been shown to be effective for phase improvement after initial phasing by molecular replacement, isomorphous replacement, anomalous dispersion or combinations of these methods. Here, a two-step process for phase determination in the X-ray structural analysis of a new coat protein from a betanodavirus, Grouper nervous necrosis virus, is described in detail. The first step is ab initio structure determination of the T = 3 icosahedral virus-like particle using NCS averaging (NCSA). The second step involves structure determination of the protrusion domain of the viral molecule using cross-crystal averaging. In this method, molecular averaging and solvent flattening constrain the electron density in real space. To quantify these constraints, a new, simple and general indicator, free fraction (ff), is introduced, where ff is defined as the ratio of the volume of the electron density that is freely changed to the total volume of the crystal unit cell. This indicator is useful and effective to evaluate the strengths of both NCSA and CCA. Under the condition that a mask (envelope) covers the target molecule well, an ff value of less than 0.1, as a new rule of thumb, gives sufficient phasing power for the successful construction of new structures. PMID- 27377381 TI - Structural basis for acyl-group discrimination by human Gcn5L2. AB - Gcn5 is a conserved acetyltransferase that regulates transcription by acetylating the N-terminal tails of histones. Motivated by recent studies identifying a chemically diverse array of lysine acyl modifications in vivo, the acyl-chain specificity of the acetyltransferase human Gcn5 (Gcn5L2) was examined. Whereas Gcn5L2 robustly catalyzes lysine acetylation, the acyltransferase activity of Gcn5L2 becomes progressively weaker with increasing acyl-chain length. To understand how Gcn5 discriminates between different acyl-CoA molecules, structures of the catalytic domain of human Gcn5L2 bound to propionyl-CoA and butyryl-CoA were determined. Although the active site of Gcn5L2 can accommodate propionyl-CoA and butyryl-CoA without major structural rearrangements, butyryl CoA adopts a conformation incompatible with catalysis that obstructs the path of the incoming lysine residue and acts as a competitive inhibitor of Gcn5L2 versus acetyl-CoA. These structures demonstrate how Gcn5L2 discriminates between acyl chain donors and explain why Gcn5L2 has weak activity for acyl moieties that are larger than an acetyl group. PMID- 27377382 TI - Second harmonic generation correlation spectroscopy for characterizing translationally diffusing protein nanocrystals. AB - Second harmonic generation correlation spectroscopy (SHG-CS) is demonstrated as a new approach to protein nanocrystal characterization. A novel line-scanning approach was performed to enable autocorrelation analysis without sample damage from the intense incident beam. An analytical model for autocorrelation was developed, which includes a correction for the optical scattering forces arising when focusing intense, infrared beams. SHG-CS was applied to the analysis of BaTiO3 nanoparticles ranging from 200 to ~500 nm and of photosystem I nanocrystals. A size distribution was recovered for each sample and compared with the size histogram measured by scanning electron microscopy (SEM). Good agreement was observed between the two independent measurements. The intrinsic selectivity of the second-order nonlinear optical process provides SHG-CS with the ability to distinguish well ordered nanocrystals from conglomerates and amorphous aggregates. Combining the recovered distribution of particle diameters with the histogram of measured SHG intensities provides the inherent hyperpolarizability per unit volume of the SHG-active nanoparticles. Simulations suggest that the SHG activity per unit volume is likely to exhibit relatively low sensitivity to the subtle distortions within the lattice that contribute to resolution loss in X-ray diffraction, but high sensitivity to the presence of multi-domain crystals. PMID- 27377384 TI - Angular-split/temporal-delay approach to ultrafast protein dynamics at XFELs. AB - X-ray crystallography promises direct insights into electron-density changes that lead to and arise from structural changes such as electron and proton transfer and the formation, rupture and isomerization of chemical bonds. The ultrashort pulses of hard X-rays produced by free-electron lasers present an exciting opportunity for capturing ultrafast structural events in biological macromolecules within femtoseconds after photoexcitation. However, shot-to-shot fluctuations, which are inherent to the very process of self-amplified spontaneous emission (SASE) that generates the ultrashort X-ray pulses, are a major source of noise that may conceal signals from structural changes. Here, a new approach is proposed to angularly split a single SASE pulse and to produce a temporal delay of picoseconds between the split pulses. These split pulses will allow the probing of two distinct states before and after photoexcitation triggered by a laser pulse between the split X-ray pulses. The split pulses originate from a single SASE pulse and share many common properties; thus, noise arising from shot-to-shot fluctuations is self-canceling. The unambiguous interpretation of ultrafast structural changes would require diffraction data at atomic resolution, as these changes may or may not involve any atomic displacement. This approach, in combination with the strategy of serial crystallography, offers a solution to study ultrafast dynamics of light-initiated biochemical reactions or biological processes at atomic resolution. PMID- 27377385 TI - Mechanism of the allosteric regulation of Streptococcus mutans 2'-deoxycytidylate deaminase. AB - In cells, dUMP is the intermediate precursor of dTTP in its synthesis during deoxynucleotide metabolism. In Gram-positive bacteria and eukaryotes, zinc dependent deoxycytidylate deaminases (dCDs) catalyze the conversion of dCMP to dUMP. The activity of dCD is allosterically activated by dCTP and inhibited by dTTP. Here, the crystal structure of Streptococcus mutans dCD (SmdCD) complexed with dTTP is presented at 2.35 A resolution, thereby solving the first pair of activator-bound and inhibitor-bound structures from the same species to provide a more definitive description of the allosteric mechanism. In contrast to the dTTP bound dCD from the bacteriophage S-TIM5 (S-TIM5-dCD), dTTP-bound SmdCD adopts an inactive conformation similar to the apo form. A structural comparison suggests that the distinct orientations of the triphosphate group in S-TIM5-dCD and SmdCD are a result of the varying protein binding environment. In addition, calorimetric data establish that the modulators bound to dCD can be mutually competitively replaced. The results reveal the mechanism underlying its regulator specific activity and might greatly enhance the understanding of the allosteric regulation of other dCDs. PMID- 27377383 TI - Structural and functional studies of the glycoside hydrolase family 3 beta glucosidase Cel3A from the moderately thermophilic fungus Rasamsonia emersonii. AB - The filamentous fungus Hypocrea jecorina produces a number of cellulases and hemicellulases that act in a concerted fashion on biomass and degrade it into monomeric or oligomeric sugars. beta-Glucosidases are involved in the last step of the degradation of cellulosic biomass and hydrolyse the beta-glycosidic linkage between two adjacent molecules in dimers and oligomers of glucose. In this study, it is shown that substituting the beta-glucosidase from H. jecorina (HjCel3A) with the beta-glucosidase Cel3A from the thermophilic fungus Rasamsonia emersonii (ReCel3A) in enzyme mixtures results in increased efficiency in the saccharification of lignocellulosic materials. Biochemical characterization of ReCel3A, heterologously produced in H. jecorina, reveals a preference for disaccharide substrates over longer gluco-oligosaccharides. Crystallographic studies of ReCel3A revealed a highly N-glycosylated three-domain dimeric protein, as has been observed previously for glycoside hydrolase family 3 beta glucosidases. The increased thermal stability and saccharification yield and the superior biochemical characteristics of ReCel3A compared with HjCel3A and mixtures containing HjCel3A make ReCel3A an excellent candidate for addition to enzyme mixtures designed to operate at higher temperatures. PMID- 27377388 TI - Extremely Well-Differentiated Gastric Adenocarcinoma Arising in Pylorus with Minor Diffuse Adenocarcinoma Component. PMID- 27377389 TI - Merkel Cell Carcinoma Metastasis to Stomach: an Infrequent Culmination of a Rare Neoplasm. PMID- 27377386 TI - Visualizing the Bohr effect in hemoglobin: neutron structure of equine cyanomethemoglobin in the R state and comparison with human deoxyhemoglobin in the T state. AB - Neutron crystallography provides direct visual evidence of the atomic positions of deuterium-exchanged H atoms, enabling the accurate determination of the protonation/deuteration state of hydrated biomolecules. Comparison of two neutron structures of hemoglobins, human deoxyhemoglobin (T state) and equine cyanomethemoglobin (R state), offers a direct observation of histidine residues that are likely to contribute to the Bohr effect. Previous studies have shown that the T-state N-terminal and C-terminal salt bridges appear to have a partial instead of a primary overall contribution. Four conserved histidine residues [alphaHis72(EF1), alphaHis103(G10), alphaHis89(FG1), alphaHis112(G19) and betaHis97(FG4)] can become protonated/deuterated from the R to the T state, while two histidine residues [alphaHis20(B1) and betaHis117(G19)] can lose a proton/deuteron. alphaHis103(G10), located in the alpha1:beta1 dimer interface, appears to be a Bohr group that undergoes structural changes: in the R state it is singly protonated/deuterated and hydrogen-bonded through a water network to betaAsn108(G10) and in the T state it is doubly protonated/deuterated with the network uncoupled. The very long-term H/D exchange of the amide protons identifies regions that are accessible to exchange as well as regions that are impermeable to exchange. The liganded relaxed state (R state) has comparable levels of exchange (17.1% non-exchanged) compared with the deoxy tense state (T state; 11.8% non-exchanged). Interestingly, the regions of non-exchanged protons shift from the tetramer interfaces in the T-state interface (alpha1:beta2 and alpha2:beta1) to the cores of the individual monomers and to the dimer interfaces (alpha1:beta1 and alpha2:beta2) in the R state. The comparison of regions of stability in the two states allows a visualization of the conservation of fold energy necessary for ligand binding and release. PMID- 27377387 TI - Comparison of full-night and ambulatory polysomnography with ApneaGraph in the subjects with obstructive sleep apnea syndrome. AB - The localization of the obstruction is crucial in determining the appropriate surgical treatment for obstructive sleep apnea syndrome (OSAS); ApneaGraph has been introduced for diagnosis of OSAS and localization of airway obstruction level. This study aims to evaluate the diagnostic value of ApneaGraph for both clinical staging and site of obstruction. Thirty male OSAS patients were prospectively enrolled in this clinical trial. The following parameter were included to the study: Body mass indexes and neck circumferences of the subjects, Epworth sleepiness scale, site of obstruction detected by flexible endoscopy and ApneaGraph, apnea hypopnea index (AHI), apnea index, hypopnea index, maximal oxygen desaturation and average oxygen saturation which were detected by both polysomnography (PSG) and ApneaGraph devices. Our data presented that, although AHI measured by ApneaGraph and PSG were significantly correlated; severity stages of the subjects were different in 44 % of the subjects when based on AHI of ApneaGraph, compared to PSG. Majority of the changes were from severe OSAS to mild or moderate levels. Similar dominant collapse levels were detected in 64 % of the subjects by both devices. It was seen that transpalatal obstruction was better correlated between ApneaGraph and flexible endoscopy. As a conclusion, we might assume that ApneaGraph can be used as a screener for OSAS and it appears to be a more reliable device to confirm dominancy of palatal level obstruction. PMID- 27377390 TI - Spiritual Well-Being and Psychological Adjustment: Mediated by Interpersonal Needs? AB - Spiritual well-being has been shown to reduce suicidal behavior, depressive symptoms, and hopelessness. Thwarted interpersonal needs have been shown to increase risk of suicidal behavior. This paper aims to explore the interrelationships among spiritual well-being, thwarted interpersonal needs, and negative outcomes including suicidal ideation, hopelessness, and depressive symptoms among African American women. Sixty-six African American women (M = 36.18; SD = 11.70), from a larger study of women who had experienced interpersonal violence within the past year, completed self-report questionnaires. Mediation analyses revealed that thwarted belongingness, but not perceived burdensomeness, significantly mediated the relations between spiritual well-being and the three outcomes. This study provides the first examination of the role of thwarted interpersonal needs on the link between spiritual well-being and negative psychological outcomes. Spiritual well-being serves a protective role against feelings of social isolation, which may reduce one's risk of negative psychological outcomes. Treatments that bolster a sense of spirituality and social connectedness may reduce suicidal ideation, hopelessness, and depressive symptoms. PMID- 27377391 TI - Government rejects BMA's call to invest extra L350m a week in NHS. PMID- 27377392 TI - Tolerability of Enteral Nutrition in Mechanically Ventilated Patients With Septic Shock Who Require Vasopressors. AB - PURPOSE: Enteral nutrition (EN) is often held in patients receiving vasopressor support for septic shock. The rationale for this practice is to avoid mesenteric ischemia. The objective of this study is to evaluate the tolerability of EN in patients with septic shock who require vasopressor support and determine factors associated with tolerance of EN. MATERIALS AND METHODS: This was a single-center retrospective review of adult patients admitted to the intensive care unit with a diagnosis of septic shock and an order for EN. The primary outcome was EN tolerance. Secondary outcomes included time to initiation of EN from the start of vasopressor(s), length of stay, and mortality. RESULTS: A total of 120 patients were included. Sixty-two percent of patients tolerated EN. The most common reason for intolerance of EN was gastric residuals > 250 mL (74%). No reports of mesenteric ischemia were observed. A multivariate analysis demonstrated that patients with septic shock initiating EN within 48 hours and receiving norepinephrine-equivalent doses of 0.14 MUg/kg/min or less were more likely to tolerate EN. CONCLUSION: Based on our observation, early EN may be tolerated and safely administered in patients with septic shock who are adequately fluid resuscitated and receive doses of < 0.14 MUg/kg/min of norepinephrine equivalents. PMID- 27377394 TI - Floor space covered by broiler chickens kept at stocking densities according to Council Directive 2007/43/EC. AB - It is controversially discussed whether the stocking densities set by the EU Directive 2007/43/EC allow a species-appropriate housing of broiler chickens. To calculate the exact area broilers occupy due to their physical size and shape, planimetric measurements using a colour-contrast method were carried out. In total, 1949 photographs of standing and 1482 of squatting chickens, taken from a top view, were analysed. A computer program counted the pixels representing the previously weighed animal in the photograph and calculated the animal area. The average area covered by chickens with 400 g live weight was 116.64+/-13.12 cm(2) in a standing and 138.61+/-12.92 cm(2) in a squatting position. These areas increased linearly as a function of live weight to 452.57+/-58.89 cm(2) (R(2)=0.90 standing) and 513.54+/-42.70 cm(2) (R(2)=0.82 squatting) at the end of the study (3200 g live weight). Squatting chickens occupied more space compared with a standing position in most of the tested weight classes (P<0.05). Depending on target weights, stocking densities and body positions, broilers occupied 48.5 77.7 per cent of 1 m(2) Thus, from a physical point of view, simultaneous resting is possible at any stocking density provided by the EU Directive and at common target weights. PMID- 27377393 TI - Drug-related hospital admissions among old people with dementia. AB - PURPOSE: Drug treatment associated problems are common and are the cause of a large proportion of hospitalizations in old people. People with dementia are especially at risk of drug-related problems. The objectives of this study were to assess the occurrence and character of drug-related problems that lead to acute hospital admissions among old people (>=65 years) with dementia or cognitive impairment. METHODS: This study was conducted in orthopedic and internal medicine wards in two hospitals in Northern Sweden. Information about acute admissions was collected from the medical records. A total of 458 people aged 65 years or older with dementia or cognitive impairment were included in the study. The contribution of drug-related problems to each hospitalization was assessed. RESULTS: Of 458 acute hospital admissions, 189 (41.3 %) were determined to be drug-related. The most common drug-related problem (86/189; 45.5 %) was an adverse drug reaction. In total, 264 drugs were judged to be involved in 189 drug related admissions, of which cardiovascular (29.5 %) and psychotropic (26.9 %) drugs were the most commonly involved drug classes. The relationship between the drug-related problem and the admission was judged certain in 25 cases, probable in 78 cases, and possible in 86 cases. Drug-related admissions were more common among people taking more drugs (p = 0.035) and among younger patients (p = 0.031). CONCLUSION: Drug-related problems appear to be responsible for a major proportion of hospitalizations among old people with dementia or cognitive impairment. Targeted interventions such as education and medication reviews may be warranted to reduce drug-related problems. PMID- 27377395 TI - Adjuvant therapy for highly malignant canine mammary tumours: Cox-2 inhibitor versus chemotherapy: a case-control prospective study. AB - Cyclooxygenase-2 (Cox-2) enzyme participates in different steps of the carcinogenetic process and in canine mammary tumours (CMTs), a high expression of Cox-2 is associated with malignancy and tumour angiogenesis. The objectives of the study were to evaluate the disease-free survival (DFS) and overall survival (OS) of a Cox-2 inhibitor as adjuvant therapy in dogs with highly malignant (HM) CMTs and compare it with that of dogs treated with chemotherapy and with control dogs. Twenty-eight dogs were prospectively included. After surgery, dogs were alternatively allocated into two treatment groups (chemotherapy with mitoxantrone n=8; Cox-2 inhibitor, firocoxib n=7). Control group (n=13) included dogs whose owners rejected adjuvant therapy. All dogs were followed up for two years or until death. The DFS was significantly higher in dogs that received adjuvant treatment (mitoxantrone or firocoxib) (P=0.030) than in control dogs. Dogs on firocoxib treatment had significantly higher DFS (P=0.015) and OS (P=0.048) than control dogs. The DFS and OS of dogs on mitoxantrone treatment were not statistically different from controls. In conclusion, this study supports the use of firocoxib for the treatment of HM-CMTs. Further studies are needed to compare the efficacy of chemotherapy drugs versus Cox-2 inhibitors as adjuvant treatment in these cases. PMID- 27377396 TI - Comparing survival of patients with single or multiple primary melanoma in the Netherlands: 1994-2009. PMID- 27377397 TI - Simple, rapid and, cost-effective fabrication of PDMS electrophoresis microchips using poly(vinyl acetate) as photoresist master. AB - This study describes a simple, rapid, and cost-effective fabrication of PDMS electrophoresis microchips using poly(vinyl acetate) (PVAc) emulsion as photoresist master. High-relief microfluidic structures were defined on poly(vinyl acetate) previously deposited on printed circuit boards surfaces without cleanroom facilities and sophisticated instrumentation. After a UV exposure, channels with heights ranging from 30 to 140 MUm were obtained by controlling the emulsion mass deposited on the master surface. The developing stage was performed using water rather than the organic solvents that are applied for conventional masks. The surface morphology was characterized by optical imaging, profilometry, and SEM. Based on the achieved results, the proposed method offers suitable reproducibility for the prototyping of electrophoresis microchips in PDMS. The feasibility of the resulting PDMS electrophoresis chips was successfully demonstrated with the separation of major inorganic cations within 100 s using a contactless conductivity detection system. The separation efficiencies ranged from ca. 67 900 to 125 600 plates/m. Due to the satisfactory performance and simplified instrumentation, we believe this fabrication protocol presents potential to be implemented in any chemical, biochemical, or biological laboratory. PMID- 27377401 TI - Continuous hydrogenation of ethyl levulinate to gamma-valerolactone and 2-methyl tetrahydrofuran over alumina doped Cu/SiO2 catalyst: the potential of commercialization. AB - Hydrogenation of levulinic acid (LA) and its esters to produce gamma valerolactone (GVL) and 2-methyl tetrahydrofuran (2-MTHF) is a key step for the utilization of cellulose derived LA. Aiming to develop a commercially feasible base metal catalyst for the production of GVL from LA, with satisfactory activity, selectivity, and stability, Al2O3 doped Cu/SiO2 and Cu/SiO2 catalysts were fabricated by co-precipitation routes in parallel. The diverse physio chemical properties of these two catalysts were characterized by XRD, TEM, dissociative N2O chemisorptions, and Py-IR methods. The catalytic properties of these two catalysts were systematically assessed in the continuous hydrogenation of ethyl levulinate (EL) in a fixed-bed reactor. The effect of acidic property of the SiO2 substrate on the catalytic properties was investigated. To justify the potential of its commercialization, significant attention was paid on the initial activity, proper operation window, by-products control, selectivity, and stability of the catalyst. The effect of reaction conditions, such as temperature and pressure, on the performance of the catalyst was also thoroughly studied. The development of alumina doped Cu/SiO2 catalyst strengthened the value-chain from cellulose to industrially important chemicals via LA and GVL. PMID- 27377402 TI - [Correction of congenital malformations by custom-made silicone implants: Contribution of computer-aided design. Experience of 611 cases]. AB - INTRODUCTION: Modern techniques of computer-aided design and tridimensional prototyping for manufacturing silicone elastomer custom implants are growing. They have widely modified the surgical indications in our unit. MATERIALS AND METHODS: By presenting their experience of 611 cases managed between 1993 and 2016, the authors describe the method of conception from CT-scans, the virtual image of the body and the manufacture of the custom-made implant perfectly adapted to the anatomy of each one. The operative techniques are described for the three main indications: the funnel chest or pectus excavatum (474 cases) according to a modified CHIN classification is corrected simply and very satisfactorily. This approach may render thoracic surgery techniques obsolete. Indeed, these operations remain risky and of doubtful functional utility; Poland syndrome (116 cases), where the use of a custom-made implant for compensation of muscle volume is frequently used, but can be improved by a transfer of adipose tissue or a classic breast implant; the leg atrophies (21 cases) receive custom elastomer implants introduced in a sub-fascial plane. RESULTS: The results are excellent for pectus excavatum but more difficult to optimize for the other two indications, requiring sometimes complementary techniques. Complications are rare and often benign, implants endure for life. Quality of life, psychological comfort and self-esteem have been improved with low morbidity and without having undergone a painful surgical experience. CONCLUSION: Reconstructive procedures of congenital malformations by custom-made silicone implants open a new field of activity for our surgical specialty with vast opportunities. PMID- 27377403 TI - Erratum to: Monitoring iCCM referral systems: Bugoye Integrated Community Case Management Initiative (BIMI) in Uganda. PMID- 27377404 TI - Testing the use of practice facilitation in a cluster randomized stepped-wedge design trial to improve adherence to cardiovascular disease prevention guidelines: HealthyHearts NYC. AB - BACKGROUND: HealthyHearts NYC (HHNYC) will evaluate the effectiveness of practice facilitation as a quality improvement strategy for implementing the Million Hearts' ABCS treatment guidelines for reducing cardiovascular disease (CVD) among high-risk patients who receive care in primary care practices in New York City. ABCS refers to (A) aspirin in high-risk individuals; (B) blood pressure control; (C) cholesterol management; and (S) smoking cessation. The long-term goal is to create a robust infrastructure for implementing and disseminating evidence-based practice guidelines (EBPG) in primary care practices. METHODS/DESIGN: We are using a stepped-wedge cluster randomized controlled trial design to evaluate the implementation process and the impact of practice facilitation (PF) versus usual care on ABCS outcomes in 250 small primary care practices. Randomization is at the practice site level, all of which begin as part of the control condition. The intervention consists of one year of PF that includes a combination of one-on-one onsite visits and shared learning across practice sites. PFs will focus on helping sites implement evidence-based components of patient-centered medical home (PCMH) and the chronic care model (CCM), which include decision support, provider feedback, self-management tools and resources, and linkages to community based services. DISCUSSION: We hypothesize that practice facilitation will result in superior clinical outcomes compared to usual care; that the effects of practice facilitation will be mediated by greater adoption of system changes in accord with PCMH and CCM; and that there will be increased adaptive reserve and change capacity. TRIAL REGISTRATION: NCT02646488. PMID- 27377405 TI - Morpho-functional variety of the coxal glands in cheyletoid mites (Prostigmata). I. Syringophilidae. AB - The anatomy and fine structure of the osmoregulatory coxal glands have been investigated in the parasitic quill mites, Syringophylopsis fringilla (Fritsch) and Torotrogla cardueli Bochkov & Mironov (Syringophilidae). In both species, tubular coxal organs are the only pair of propodosomal glands, whereas in most Prostigmata, several acinous (salivary) glands are also present entering a pair of podocephalic canals, which are continuations of the coxal glands' excretory ducts. In the adults and tritonymphs of the quill mites, the coxal glands show the same basic morphology with slight differences in their packing mode between the studied species. A filtering sacculus is absent. Each gland consists of a long tubular gland body comprising 4 to 6 longitudinal trunks and a cuticle-lined excretory duct continuous into the podocephalic canal. The gland body is composed of 4 morphologically distinct regions: proximal and distal tubes followed by the two granule-containing regions denoted as the "violet" and "green" gland portions. Electron microscopy showed the epithelium of the proximal and distal tubes to be rich in deep apical membrane invaginations associated with branched pinocytotic canals or vacuoles, especially extensive in the distal tube. A number of large mitochondria are concentrated basally to maintain ionic and water transport. The enlarged penultimate "violet" portion is composed of high epithelial cells that show certain endocytotic activity and also produce a large amount of uniform secretory granules derived from numerous small Golgi bodies. The terminal "green" portion produces dense protein-like inclusions and might functionally substitute lost salivary glands. The fine structure of the podocephalic canal is also thoroughly described and compared to the information available in the literature. PMID- 27377406 TI - Noncoding RNAs in the regulation of skeletal muscle biology in health and disease. AB - Skeletal muscle is composed of multinucleated myofibers that arise from the fusion of myoblasts during development. Skeletal muscle is essential for various body functions such as maintaining posture, locomotion, breathing, and metabolism. Skeletal muscle undergoes remarkable adaptations in response to environmental stimuli leading to atrophy or hypertrophy. Moreover, degeneration of skeletal muscle is a common feature in a number of muscular disorders including muscular dystrophy. Emerging evidence suggests that noncoding RNAs, such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are critical for skeletal muscle physiology. Several miRNAs and lncRNAs have now been found to control skeletal muscle development and regeneration. Noncoding RNAs also play an important role in the regulation of skeletal muscle mass in adults. Furthermore, aberrant expression of miRNAs and lncRNAs has been observed in several muscular disorders. In this article, we discuss the mechanisms of action of miRNAs and lncRNAs in skeletal muscle formation, growth, regeneration, and disease. We further highlight potential therapeutic strategies for utilizing noncoding RNAs to improve skeletal muscle function. PMID- 27377407 TI - Lifestyle in Multiple Myeloma - a longitudinal cohort study protocol. AB - BACKGROUND: Deterioration in bone health is one of the presenting symptoms of Multiple Myeloma (MM), a cancer of plasma cells. As a consequence of this condition, patients suffer bone pain and bone damage and report cancer-related fatigue, resulting in deterioration in their quality of life. Evidence in patients with solid tumours shows promise for the positive effects of physical activity on quality of life. However, in the case of patients with MM a better understanding of the association between physical fitness and quality of life factors is still required. Therefore, this cohort study aims to objectively and longitudinally assess activity and fitness levels in patients with MM in order to explore their role in bone health, fatigue and quality of life for this patient population. METHODS/DESIGN: The study is a prospective cohort study of MM patients in remission to assess physical activity, fatigue and bone health. Clinical markers of health, self-reported measures of psychological and physical well-being, and lifestyle behaviours are assessed at baseline, 3, 6 and 12 months. At each time point, patients complete cardiopulmonary exercise testing (CPET) along with a series of objective tests to assess physical fitness (eg accelerometry) and a number of self-report measures. A complementary qualitative study will be carried out in order to explore patients' desire for lifestyle advice and when in their cancer journey they deem such advice to be useful. DISCUSSION: This study will be the first to prospectively and longitudinally explore associations between physical fitness and well-being, bone health, and fatigue (along with a number of other physical and clinical outcomes) in a cohort of patients with MM with the use of objective measures. The findings will also help to identify time points within the MM pathway at which physical activity interventions may be introduced for maximum benefit. PMID- 27377408 TI - Mental health help seeking patterns and associations among Australian same sex attracted women, trans and gender diverse people: a survey-based study. AB - BACKGROUND: Same sex attracted women (SSAW) are disproportionately affected by depression and anxiety, due to experiences of sexuality and gender based discrimination. They access mental health services at higher rates than heterosexual women, however with lower levels of satisfaction. This study examined the range of professional and social help seeking by same-sex attracted women, and patterns according to sexual orientation and gender identity subgroup. METHODS: Eight key stakeholders were interviewed, and a convenience sample of 1628 Australian SSAW completed an online survey in 2015. This included several scales to measure mental health, community connectedness and resilience; and measured past 12 month help seeking behaviour, enablers, barriers and preferences for mental health care. Chi-square analyses and binary logistic regression analyses examined demographic associations with mental health. Correlations between help seeking, mental and physical health, and connectedness were run. RESULTS: A high proportion (80 %) of the total sample had perceived mental health problems over the past 12 months. Over half had depression, and over 96 % had anxiety. Trans and gender diverse participants were twice as likely as female participants to have mental health problems, and lesbians were least likely. High levels of past 12 month help seeking included 74.4 % seeing a GP, 44.3 % seeing a psychologist/counsellor, 74.7 % seeking family/friends support and 55.2 % using internet based support. Professional help was prioritised by those with higher mental health need. Trans participants were most likely to have sought professional help and participated in support groups, but least likely to have sought help from friends or family. The most common barriers to help seeking were discrimination and lack of LGBTI sensitivity of services, particularly for gender diverse, queer and pansexual participants. Enablers included mainstream community connectedness, having a trustworthy GP, and encouragement by friends. CONCLUSIONS: Mental health services need to be LGBTI inclusive and to understand the emerging diverse sexual and gender identities. Peer support is an important adjunct to professional support, however may not be fully meeting the needs of some identity sub-groups. Mental health promotion should be tailored for diverse sub-groups to build mental health literacy and resilience in the face of ongoing discrimination. PMID- 27377410 TI - Spatiotemporal dataset on Chinese population distribution and its driving factors from 1949 to 2013. AB - Spatio-temporal data on human population and its driving factors is critical to understanding and responding to population problems. Unfortunately, such spatio temporal data on a large scale and over the long term are often difficult to obtain. Here, we present a dataset on Chinese population distribution and its driving factors over a remarkably long period, from 1949 to 2013. Driving factors of population distribution were selected according to the push-pull migration laws, which were summarized into four categories: natural environment, natural resources, economic factors and social factors. Natural environment and natural resources indicators were calculated using Geographic Information System (GIS) and Remote Sensing (RS) techniques, whereas economic and social factors from 1949 to 2013 were collected from the China Statistical Yearbook and China Compendium of Statistics from 1949 to 2008. All of the data were quality controlled and unified into an identical dataset with the same spatial scope and time period. The dataset is expected to be useful for understanding how population responds to and impacts environmental change. PMID- 27377409 TI - miR-155 in the progression of lung fibrosis in systemic sclerosis. AB - BACKGROUND: MicroRNA (miRNA) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from patients with SSc-ILD. A chronic lung fibrotic murine model was used. METHODS: RNA was isolated from lung tissue of 12 patients with SSc-ILD and 5 controls. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. Lung fibroblasts and peripheral blood mononuclear cells (PBMC) were isolated from healthy controls and patients with SSc-ILD. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DNA Intelligent Analysis (DIANA)-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. RESULTS: Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q < 0.25). DIANA-miRPath revealed 57 Kyoto Encyclopedia of Genes and Genomes pathways related to the most dysregulated miRNA. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts only mildly expressed miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and weaker lung induction of several genes after bleomycin exposure compared to wild type mice. CONCLUSIONS: miRNA are dysregulated in the lungs and PBMC of patients with SSc-ILD. Based on mRNA-miRNA interaction analysis and pathway tools, miRNA may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD. PMID- 27377411 TI - Survival and expression of acid resistance genes in Shiga toxin-producing Escherichia coli acid adapted in pineapple juice and exposed to synthetic gastric fluid. AB - AIMS: The aim of this research was to determine the ability of non-O157 Shiga toxin-producing Escherichia coli (STEC) serogroups to survive with exposure to synthetic gastric fluid (SGF) after adaptation to pineapple juice (PJ) at room and refrigerated temperatures compared to E. coli O157:H7 and to examine the relative transcriptional expression of acid resistance (AR) genes, rpoS, gadA and adiA. METHODS AND RESULTS: Resistant and sensitive strains belonging to five different STEC serogroups (O26, O103, O104, O111 and O157; n = 10) were used in this study. All strains were adapted in PJ (pH 3.8) stored at 4 and 20 degrees C for 24 h, and then the relative transcription levels of genes in all strains were quantified using a real-time quantitative-PCR assay. After adaptation in PJ, the STEC strains were exposed to SGF (pH 1.5 and 2.0) at 37 degrees C for 2 h. Generally, the STEC adapted in PJ at 4 degrees C displayed enhanced survival compared to acid adaptation in PJ at 20 degrees C and nonadapted controls with exposure to SGF (P < 0.05). Moreover, resistant strains exhibited higher survival rates compared to sensitive strains (P < 0.05). Overall, adaptation at 4 degrees C resulted in significantly (P < 0.05) enhanced gene expression levels in PJ, and transcript levels of gadA were higher than those of the rpoS and adiA genes. CONCLUSIONS: The up-regulation of AR genes due to adaptation in PJ at low temperature may increase STEC survival in acidic environments such as the gastrointestinal tract. Some non-O157 STEC strains, including serotypes O103:H2 and O111:H8, showed relatively high AR levels similar to those of STEC O157:H7. SIGNIFICANCE AND IMPACT OF THE STUDY: Induction of AR genes in acidic fruit juice, and potentially in other acidic foods may increase the risk of foodborne illness by non-O157 STEC serogroups. PMID- 27377412 TI - Classification of CFTR mutation classes. PMID- 27377413 TI - Classification of CFTR mutation classes - Authors' reply. PMID- 27377414 TI - Classification of CFTR mutation classes. PMID- 27377415 TI - Treatment landscape of metastatic prostate cancer: the role of radium-223. AB - The landscape of metastatic prostate cancer has changed recently with the availability of six new molecules showing an overall survival benefit. The development of compounds able to decrease the rate of complications from bone metastasis has also led to improvements in overall morbidity associated with this disease. In this paper, we briefly review the currently available drugs indicated in the treatment of metastatic prostate cancer, focusing on the place of the radiopharmaceutical agent radium-223 and its very unique mechanism of action and safety profile. PMID- 27377418 TI - Selective prevention of combat-related post-traumatic stress disorder using attention bias modification training: a randomized controlled trial. AB - BACKGROUND: Efficacy of pre-trauma prevention for post-traumatic stress disorder (PTSD) has not yet been established in a randomized controlled trial. Attention bias modification training (ABMT), a computerized intervention, is thought to mitigate stress-related symptoms by targeting disruptions in threat monitoring. We examined the efficacy of ABMT delivered before combat in mitigating risk for PTSD following combat. METHOD: We conducted a double-blind, four-arm randomized controlled trial of 719 infantry soldiers to compare the efficacy of eight sessions of ABMT (n = 179), four sessions of ABMT (n = 184), four sessions of attention control training (ACT; n = 180), or no-training control (n = 176). Outcome symptoms were measured at baseline, 6-month follow-up, 10 days following combat exposure, and 4 months following combat. Primary outcome was PTSD prevalence 4 months post-combat determined in a clinical interview using the Clinician-Administered PTSD Scale. Secondary outcomes were self-reported PTSD and depression symptoms, collected at all four assessments. RESULTS: PTSD prevalence 4 months post-combat was 7.8% in the no-training control group, 6.7% with eight session ABMT, 2.6% with four-session ABMT, and 5% with ACT. Four sessions of ABMT reduced risk for PTSD relative to the no-training condition (odds ratio 3.13, 95% confidence interval 1.01-9.22, p < 0.05, number needed to treat = 19.2). No other between-group differences were found. The results were consistent across a variety of analytic techniques and data imputation approaches. CONCLUSIONS: Four sessions of ABMT, delivered prior to combat deployment, mitigated PTSD risk following combat exposure. Given its low cost and high scalability potential, and observed number needed to treat, research into larger-scale applications is warranted. The ClinicalTrials.gov identifier is NCT01723215. PMID- 27377419 TI - Shortening of the electromechanical window in the ketamine/xylazine-anesthetized guinea pig model to assess pro-arrhythmic risk in early drug development. AB - BACKGROUND: A negative electromechanical window (EMw) was recently proposed as a better preclinical tool than QTc interval to predict clinical pro-arrhythmic potential. As such, we utilized the ketamine/xylazine anesthetized guinea pig to characterize the EMw and QTc interval for a diverse set of reference agents with known clinical pro-arrhythmic potential. Then we determined the clinical proarrhythmia predictive capacity of EMw shortening compared to hERG inhibition or QTc interval prolongation alone. METHODS: Changes in EMw and QTc interval by 26 reference agents were evaluated in the ketamine/xylazine-anesthetized guinea pig. Confusion matrix analysis using the hERG, QTc and EMw indexes (hERG IC50, QTc EC5 or the EMw EC-10 divided by their respective free therapeutic maximal plasma concentration) at various folds the therapeutic concentrations was conducted to assess the concordance of each index to predict clinical pro arrhythmic risk. RESULTS: Shortening of the EMw concomitant to an increase in QTc interval was observed in the GP with known pro-arrhythmic drugs. Non-torsadogenic compounds did not cause EMw shortening, although some prolonged the QTc interval. The preclinical:clinical concordance of the EMw index (88%) was similar (p>0.05) to using QTc interval prolongation alone (85%) but significantly greater (p<0.05) than using hERG inhibition alone (69%). In addition, the specificity when using the EMw (87%) was largely greater (p<0.05) than using QTc interval (73%) or hERG inhibition (60%) alone. When the components of the response (duration of left ventricular pressure (LVP) cycle (QLVPend) or QT interval) that caused EMw shortening were considered, the concordance is further improved (>95%). CONCLUSION: EMw shortening improves QTc interval prolongation recording in early drug development and increases the translatability over existing preclinical tools in predicting clinical arrhythmias. PMID- 27377417 TI - Psychiatric disorders biochemical pathways unraveled by human brain proteomics. AB - Approximately 25 % of the world population is affected by a mental disorder at some point in their life. Yet, only in the mid-twentieth century a biological cause has been proposed for these diseases. Since then, several studies have been conducted toward a better comprehension of those disorders, and although a strong genetic influence was revealed, the role of these genes in disease mechanism is still unclear. This led most recent studies to focus on the molecular basis of mental disorders. One line of investigation that has risen in the post-genomic era is proteomics, due to its power of revealing proteins and biochemical pathways associated with biological systems. Therefore, this review compiled and analyzed data of differentially expressed proteins, which were found in postmortem brain studies of the three most prevalent psychiatric diseases: schizophrenia, bipolar disorder and major depressive disorders. Overviewing both the proteomic methods used in postmortem brain studies, the most consistent metabolic pathways found altered in these diseases. We have unraveled those disorders share about 21 % of proteins affected, and though most are related to energy metabolism pathways deregulation, the main differences found are 14-3-3 mediated signaling in schizophrenia, mitochondrial dysfunction in bipolar disorder and oxidative phosphorylation in depression. PMID- 27377420 TI - Adolescent Pregnancy and Smoking in West Virginia: Pregnancy Risk Assessment Monitoring System (PRAMS) 2005-2010. AB - Objective The purpose of this study was to examine the association between prenatal smoking and small for gestational age (SGA) infants among adolescent women in West Virginia, taking into account sociodemographic and health-related factors. Methods Secondary data analysis was conducted using the 2005-2010 West Virginia Pregnancy Risk Assessment and Monitoring Systems weighted dataset. The study population using complete case analysis procedure consisted of 886 adolescent women ages 19 and younger who delivered a live singleton infant in West Virginia. Results The prevalence of smoking among adolescents during the last 3 months of pregnancy was 67 %. Nearly a quarter (22.0 %) of the adolescents gave birth to SGA infants. Results from the logistic regression analysis showed that after controlling for sociodemographic and health-related variables, adolescents who smoked during the last 3 months of pregnancy were more likely to have SGA infants than those who did not smoke during the last 3 months of pregnancy (OR = 1.86, 95 % CI 1.06-3.27, P = 0.0307). Conclusion This study highlights the importance of recognizing that prenatal smoking is an issue among West Virginia adolescents and the need for evidence-based, culturally, and developmentally appropriate interventions for this Appalachian population. PMID- 27377422 TI - Noninvasive fractional flow reserve derived from coronary computed tomography angiography for identification of ischemic lesions: a systematic review and meta analysis. AB - Detection of coronary ischemic lesions by fractional flow reserve (FFR) has been established as the gold standard. In recent years, novel computer based methods have emerged and they can provide simulation of FFR using coronary artery images acquired from coronary computed tomography angiography (FFRCT). This meta analysis aimed to evaluate diagnostic performance of FFRCT using FFR as the reference standard. Databases of PubMed, Cochrane Library, EMBASE, Medion and Web of Science were searched. Seven studies met the inclusion criteria, including 833 stable patients (1377 vessels or lesions) with suspected or known coronary artery disease (CAD). The patient-based analysis showed pooled estimates of sensitivity, specificity and diagnostic odds ratio (DOR) for detection of ischemic lesions were 0.89 [95%confidence interval (CI), 0.85-0.93], 0.76 (95%CI, 0.64-0.84) and 26.21 (95%CI, 13.14-52.28). At a per-vessel or per-lesion level, the pooled estimates were as follows: sensitivity 0.84 (95%CI, 0.80-0.87), specificity 0.76 (95%CI, 0.67-0.83) and DOR 16.87 (95%CI, 9.41-30.25). Area under summary receiver operating curves was 0.90 (95%CI, 0.87-0.92) and 0.86 (95%CI, 0.83-0.89) at the two analysis levels, respectively. In conclusion, FFRCT technology achieves a moderate diagnostic performance for noninvasive identification of ischemic lesions in stable patients with suspected or known CAD in comparison to invasive FFR measurement. PMID- 27377423 TI - Oral cancer during pregnancy. PMID- 27377424 TI - Unmet needs for patients with salivary gland cancer. PMID- 27377421 TI - Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes. AB - Synchronous colorectal cancers (syCRCs) are physically separated tumours that develop simultaneously. To understand how the genetic and environmental background influences the development of multiple tumours, here we conduct a comparative analysis of 20 syCRCs from 10 patients. We show that syCRCs have independent genetic origins, acquire dissimilar somatic alterations, and have different clone composition. This inter- and intratumour heterogeneity must be considered in the selection of therapy and in the monitoring of resistance. SyCRC patients show a higher occurrence of inherited damaging mutations in immune related genes compared to patients with solitary colorectal cancer and to healthy individuals from the 1,000 Genomes Project. Moreover, they have a different composition of immune cell populations in tumour and normal mucosa, and transcriptional differences in immune-related biological processes. This suggests an environmental field effect that promotes multiple tumours likely in the background of inflammation. PMID- 27377426 TI - Comparison of the ipsi-lateral versus contra-lateral retrograde approach of percutaneous coronary interventions in chronic total occlusions. AB - BACKGROUND: Retrograde recanalization of coronary chronic total occlusions (CTO) via contralateral (CL) collateral connections (CCs) is successful in 60-70% of patients in whom conventional antegrade approach fails or is unpromising. This study describes our experience with retrograde CTO-PCI via ipsi-lateral (IL) CCs in patients with unfavorable CL CCs. METHODS: Between January 2013 and September 2015, 392 consecutive CTO procedures were performed by two high volume CTO operators and the relevant data were fed into an online registry (ERCTO(r) EuroCTO-club). Most patients (222/392; 57%) were approached antegradely, whereas 43% were attempted retrogradely (170/392). After exclusion of all procedures performed via bypass-grafts (n = 12), PCI via CL CCs, the CL-group (n = 114/158; 72%), was compared with the IL-group that was attempted via IL CCs (n = 44/158; 28%). RESULTS: Both groups were similar with respect to risk factors and morphologic criteria of CTO-severity. The initial primary strategy was successful in 78% in the CL-group and in 68% in the IL-group. In both patient groups, the initial strategy had to be switched in five patients from CL toward IL (4.4%, n = 5/114) and from IL to CL (11.3% n = 5/44). The rate of major complications was 7% (CL) and 5% (IL), respectively (n.s.). After retrograde failure and cross-over to an antegrade controlled re-entry strategy the overall success rates increased to 92% (CL) and 93% (IL). CONCLUSIONS: In experienced hands retrograde CTO-PCI via IL CCs appears as safe and successful as the CL approach. (c) 2016 Wiley Periodicals, Inc. PMID- 27377425 TI - Obesity and associated lifestyles modify the effect of glucose metabolism-related genetic variants on impaired glucose homeostasis among postmenopausal women. AB - PURPOSE: Impaired glucose metabolism-related genetic variants likely interact with obesity-modifiable factors in response to glucose intolerance, yet their interconnected pathways have not been fully characterized. METHODS: With data from 1,027 postmenopausal participants of the Genomics and Randomized Trials Network study and 15 single-nucleotide polymorphisms (SNPs) associated with glucose homeostasis, we assessed whether obesity, physical activity, and high dietary fat intake interact with the SNP-glucose variations. We used regression analysis plus stratification and graphic approaches. RESULTS: Across carriers of the 15 SNPs, fasting levels of glucose, insulin, and homeostatic model assessment insulin resistance (HOMA-IR) were higher in obese, inactive, and high fat-diet women than in their respective counterparts. Carriers within subgroups differently demonstrated the direction and/or magnitude of the variants' effect on glucose-relevant traits. Variants in GCKR, GCK, DGKB/TMEM195 (P for interactions = 0.02, 0.02, and 0.01), especially, showed interactions with obesity: obese, inactive, and high fat-diet women had greater increases in fasting glucose, insulin, and HOMA-IR levels. Obese carriers at TCF7L2 variant had greater increases in fasting glucose levels than nonobese carriers (P for interaction = 0.04), whereas active women had greater decreases in insulin and HOMA-IR levels than inactive women (P for interaction = 0.02 in both levels). CONCLUSIONS: Our data support the important role of obesity in modifying glucose homeostasis in response to glucose metabolism-relevant variants. These findings may inform research on the role of glucose homeostasis in the etiology of chronic disease and the development of intervention strategies to reduce risk in postmenopausal women. PMID- 27377427 TI - On the distribution of intranuclear and cytoplasmic aggregates in the brainstem of patients with spinocerebellar ataxia type 2 and 3. AB - The polyglutamine (polyQ) diseases are a group of genetically and clinically heterogeneous neurodegenerative diseases, characterized by the expansion of polyQ sequences in unrelated disease proteins, which form different types of neuronal aggregates. The aim of this study was to characterize the aggregation pathology in the brainstem of spinocerebellar ataxia type 2 (SCA2) and 3 (SCA3) patients. For good recognition of neurodegeneration and rare aggregates, we employed 100 um PEG embedded brainstem sections, which were immunostained with the 1C2 antibody, targeted at polyQ expansions, or with an antibody against p62, a reliable marker of protein aggregates. Brainstem areas were scored semiquantitatively for neurodegeneration, severity of granular cytoplasmic staining (GCS) and frequency of neuronal nuclear inclusions (NNI). SCA2 and SCA3 tissue exhibited the same aggregate types and similar staining patterns. Several brainstem areas showed statistically significant differences between disease groups, whereby SCA2 showed more severe GCS and SCA3 showed more numerous NNI. We observed a positive correlation between GCS severity and neurodegeneration in SCA2 and SCA3 and an inverse correlation between the frequency of NNI and neurodegeneration in SCA3. Although their respective disease proteins are unrelated, SCA2 and SCA3 showed the same aggregate types. Apparently, the polyQ sequence alone is sufficient as a driver of protein aggregation. This is then modified by protein context and intrinsic properties of neuronal populations. The severity of GCS was the best predictor of neurodegeneration in both disorders, while the inverse correlation of neurodegeneration and NNI in SCA3 tissue implies a protective role of these aggregates. PMID- 27377428 TI - Morphological convergence in the pubis of slow-moving primates and xenarthrans. AB - OBJECTIVES: Determining the functional significance of pubic rami is important for reconstructing locomotor behavior of fossil species. The slow loris pelvis, characterized by long pubic rami, is unusual among primates. Long pubic rami may be related to increasing the moment arm of the abdominal musculature during ventroflexion after the termination of hindlimb suspension, which is a common component of slow arboreal quadrupedalism (AQ). Some extant xenarthran species are also slow AQ taxa, and provide an ideal group to test hypotheses of morphologically convergent adaptations to slow AQ. MATERIALS AND METHODS: A model relating abdominal moment arms to pubic morphology is tested in three genera of slow-moving xenarthrans (Bradypus, Choloepus, and Cyclopes) and two species of slow loris (Nycticebus coucang and Perodicticus potto), using a comparative sample of 37 species of primates and xenarthrans. Phylogenetic analyses of variance and regression were performed on pubic dimensions (superior and inferior pubic ramus length, pubic symphysis length). RESULTS: As a locomotor group, slow moving xenarthrans and lorises share superior pubic rami that are longer than all other locomotor groups; at the species level, there is some overlap among slow AQ and non-slow-AQ taxa. Inferior pubic ramus and pubic symphysis lengths also differ according to locomotor category, but multiple comparisons among locomotor groups are non-significant. DISCUSSION: These results support the hypothesis that superior pubic ramus length is functionally related to slow, suspensory locomotion by increasing the leverage of the ventral abdominal musculature, and demonstrates morphological convergence among two phylogenetically distant groups of mammals that have evolved adaptations for slow, suspensory locomotion. PMID- 27377430 TI - Recombinant C-terminal 311 amino acids of HapS adhesin as a vaccine candidate for nontypeable Haemophilus influenzae: A study on immunoreactivity in Balb/C mouse. AB - Hap, an auto-transporter protein, is an antigenically conserved adhesion protein which is present on both typeable and nontypeable Haemophilus influenzae. This protein has central role in bacterial attachment to respiratory tract epithelial cells. A 1000bp C-terminal fragment of Hap passenger domain (HapS) from nontypeable Haemophilus influenzae was cloned into a prokaryotic expression vector, pET-24a. BALB/c mice were immunized subcutaneously with purified rC-HapS. Serum IgG responses to purified rC-HapS, serum IgG subclasses were determined by ELISA and functional activity of antibodies was examined by Serum Bactericidal Assay. The output of rC-HapS was approximately 62% of the total bacterial proteins. Serum IgG responses were significantly increased in immunized group with rC-HapS mixed with Freund's adjuvant in comparison with control groups. Analysis of the serum IgG subclasses showed that the IgG1 subclass was predominant after subcutaneous immunization in BALB/c mice (IgG2a/IgG1 < 1). The sera from rC-HapS immunized animals were strongly bactericidal against nontypeable Haemophilus influenzae. These results suggest that rC-HapS may be a potential vaccine candidate for nontypeable Haemophilus influenzae. PMID- 27377429 TI - The Efficacy and Cost-Effectiveness of Stepped Care Prevention and Treatment for Depressive and/or Anxiety Disorders: A Systematic Review and Meta-Analysis. AB - Stepped care is an increasingly popular treatment model for common mental health disorders, given the large discrepancy between the demand and supply of healthcare service available. In this review, we aim to compare the efficacy and cost-effectiveness of stepped care prevention and treatment with care-as-usual (CAU) or waiting-list control for depressive and/or anxiety disorders. 5 databases were utilized from its earliest available records up until April 2015. 10 randomized controlled trials were included in this review, of which 6 examined stepped care prevention and 4 examined stepped care treatment, specifically including ones regarding depressive and/or anxiety disorders. Only trials with self-help as a treatment component were included. Results showed stepped care treatment revealed a significantly better performance than CAU in reducing anxiety symptoms, and the treatment response rate of anxiety disorders was significantly higher in stepped care treatment than in CAU. No significant difference was found between stepped care prevention/treatment and CAU in preventing anxiety and/or depressive disorders and improving depressive symptoms. In conclusion, stepped care model appeared to be better than CAU in treating anxiety disorders. The model has the potential to reduce the burden on existing resources in mental health and increase the reach and availability of service. PMID- 27377431 TI - Hepatic cholinesterase of laying hens naturally infected by Salmonella Gallinarum (fowl typhoid). AB - Salmonella is a facultative intracellular pathogen that may cause foodborne gastroenteritis in humans and animals consisting of over 2000 serovars. The serovar Salmonella Gallinarum is an important worldwide pathogen of poultry. However, little is known on the mechanisms of pathogenesis of Salmonella in chickens. The aim of this study was to evaluate cholinesterase and myeloperoxidase activities in hepatic tissue of laying hens naturally infected by S. Gallinarum. Twenty positive liver samples for S. Gallinarum were collected, in addition to seven liver samples from healthy uninfected laying hens (control group). The right liver lobe was homogenized for analysis of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and myeloperoxidase (MPO), and the left lobe was divided into two fragments, one for histopathology and the other for Salmonella isolation. The results showed changes in AChE and BchE activity in the liver of infected laying hens compared to the control group (P < 0.05), i.e. reduced AChE and increased BChE activities in liver samples. Infected animals showed increased MPO activity compared to healthy animals (P < 0.05). Furthermore, the histopathological findings showed fibrinoid necrosis associated to the infiltration of lymphocytes, plasma cells, macrophages,heterophils in the liver of infected hens. These findings suggest that the inflammatory process was attenuated providing a pro-inflammatory action of both enzyme analyzed in order to reduce the free ACh, a molecule which has an anti-inflammatory action. Therefore, our results lead to the hypothesis that cholinesterase plays an important role on the modulation of immune response against S. Gallinarum with an inflammatory effect, contributing to the response against this bacterium. This study should contribute to a better understanding on the pathogenic mechanisms involved in laying hens infected by S. Gallinarum. PMID- 27377433 TI - [Mineral trioxide aggregate (MTA) a success story in apical surgery]. AB - The objective of apical surgery is to retain teeth with persistent apical pathosis following orthograde root canal treatment if endodontic non-surgical revision is difficult or associated with risks, or is even declined by the patient. Since the most frequent cause of recurrent apical disease is bacterial reinfection from the (remaining) root canal system, the bacteria-tight root-end filling is the most important step in apical surgery. In the early 1990s, mineral trioxide aggregate (MTA) was developed at the Loma Linda University in California/USA. Preclinical studies clearly showed that MTA has a high sealing capability, a good material stability and an excellent biocompatbility. Multiple experimental studies in animals highlighted the mild tissue reactions observed adjacent to this material. Furthermore, histological analysis of the periapical regions demonstrated a frequent deposition of new cementum not only onto the resection plane (cut dentinal surface), but also directly onto MTA. For these reasons, MTA is considered a bioactive material. In 1997 MTA was cleared for clinical use in patients. Multiple prospective clinical and randomized studies have documented high and constant success rates of MTA-treated teeth in apical surgery. A recently published longitudinal study showed that MTA-treated teeth remained stable over five years; hence the high healed rates documented after one year are maintained during long-term observation. PMID- 27377432 TI - New approaches in tail-bleeding assay in mice: improving an important method for designing new anti-thrombotic agents. AB - This report describes a modified, simple, low-cost and more sensitive method to determine bleeding patterns and haemoglobin concentration in a tail-bleeding assay using BALB/c mice and tail tip amputation. The cut tail was immersed in Drabkin's reagent to promote erythrocyte lysis and haemoglobin release, which was monitored over 30 min. The operator was blinded to individual conditions of the mice, which were treated with either saline (NaCl 0.15m), DMSO (0.5%) or clinical anti-thrombotic drugs. Our experimental protocols showed good reproducibility and repeatability of results when using Drabkin's reagent than water. Thus, the use of Drabkin's reagent offered a simple and low-cost method to observe and quantify the bleeding and rebleeding episodes. We also observed the bleeding pattern and total haemoglobin loss using untreated animals or those under anti-coagulant therapy in order to validate the new Drabkin method and thus confirm that it is a useful protocol to quantify haemoglobin concentrations in tail-bleeding assay. This modified method provided a more accurate results for bleeding patterns in mice and for identifying new anti-thrombotic drugs. PMID- 27377434 TI - 1,2-Alkylarylation of Styrenes with alpha-Carbonyl Alkyl Bromides and Indoles Using Visible-Light Catalysis. AB - A new intermolecular 1,2-alkylarylation of styrenes with alpha-carbonyl alkyl bromides and indoles using fac-[Ir(ppy)3] as the photoredox catalyst has been developed. The method allows the simultaneous formation of two new carbon-carbon bonds through three component reaction, and represents a new single-electron transfer (SET) strategy for the 1,2-alkylarylation of the styrenes with broad substrate scope and excellent functional group tolerance. PMID- 27377435 TI - Objective and perceptual comparisons of two bluetooth hearing aid assistive devices. AB - PURPOSE: With the advent of Bluetooth technology, many of the assistive listening devices for hearing have become manufacturer specific, with little objective information about the performance provided. METHOD: Thirty native English speaking adults (mean age 29.8) with normal hearing were tested pseudo-randomly with two major hearing aid manufacturers' proprietary Bluetooth connectivity devices paired to the accompanying manufacturer's specific hearing aids. Sentence recognition performance was objectively measured for each system with signals transmitted via a land-line to the same iPhone in two conditions. RESULTS: There was a significant effect of participant's performance according to listening condition. There was no significant effect between device manufacturers according to listening condition, but there was a significant effect in participant's perception of "quality of sound". CONCLUSIONS: Despite differences in signal transmission for each devise, when worn by participants both the systems performed equally. In fact, participants expressed personal preferences for specific technology that was largely due to their perceived quality of sound while listening to recorded signals. While further research is necessary to investigate other measures of benefit for Bluetooth connectivity devices, preliminary data suggest that in order to ensure comfort and compatibility, not only should objective measures of the patient benefit be completed, but also assessing the patient's perception of benefit is equally important. Implications for Rehabilitation All professionals who work with individuals with hearing loss, become aware of the differences in the multiple choices for assistive technology readily available for hearing loss. With the ever growing dispensing of Bluetooth connectivity devices coupled to hearing aids, there is an increased burden to determine whether performance differences could exist between manufacturers. There is a growing need to investigate other measures of benefit for Bluetooth hearing aid connectivity devices that not only include objective measures, but also patient perception of benefit. PMID- 27377437 TI - Synthesis of a Molecule with Four Different Adjacent Pnictogens. AB - The synthesis of a molecule containing four adjacent different pnictogens was attempted by conversion of a Group 15 allyl analogue anion [Mes*NAsPMes*](-) (Mes*=2,4,6-tri-tert-butylphenyl) with antimony(III) chloride. A suitable precursor is Mes*N(H)AsPMes* (1) for which several syntheses were investigated. The anions afforded by deprotonation of Mes*N(H)AsPMes* were found to be labile and, therefore, salts could not be isolated. However, the in situ generated anions could be quenched with SbCl3 , yielding Mes*N(SbCl2 )AsPMes* (4). PMID- 27377438 TI - Tissue-Engineered Fibrin-Based Heart Valve with Bio-Inspired Textile Reinforcement. AB - The mechanical properties of tissue-engineered heart valves still need to be improved to enable their implantation in the systemic circulation. The aim of this study is to develop a tissue-engineered valve for the aortic position - the BioTexValve - by exploiting a bio-inspired composite textile scaffold to confer native-like mechanical strength and anisotropy to the leaflets. This is achieved by multifilament fibers arranged similarly to the collagen bundles in the native aortic leaflet, fixed by a thin electrospun layer directly deposited on the pattern. The textile-based leaflets are positioned into a 3D mould where the components to form a fibrin gel containing human vascular smooth muscle cells are introduced. Upon fibrin polymerization, a complete valve is obtained. After 21 d of maturation by static and dynamic stimulation in a custom-made bioreactor, the valve shows excellent functionality under aortic pressure and flow conditions, as demonstrated by hydrodynamic tests performed according to ISO standards in a mock circulation system. The leaflets possess remarkable burst strength (1086 mmHg) while remaining pliable; pronounced extracellular matrix production is revealed by immunohistochemistry and biochemical assay. This study demonstrates the potential of bio-inspired textile-reinforcement for the fabrication of functional tissue-engineered heart valves for the aortic position. PMID- 27377439 TI - Bioinspired Collagen-Apatite Nanocomposites for Bone Regeneration. AB - INTRODUCTION: Natural bone has a complex hierarchical nanostructure composed of well-organized collagen fibrils embedded with apatite crystallites. Bone tissue engineering requires scaffolds with structural properties and functionality similar to the natural bone. Inspired by bone, a collagen-apatite (Col-Ap) nanocomposite was fabricated with bonelike subfibrillar nanostructures using a modified bottom-up biomimetic approach and has a potential role in the healing of large bone defects in unresolved apical periodontitis. METHODS: The bone regeneration potential of the Col-Ap nanocomposite was investigated by comparing it with inorganic beta-tricalcium phosphate and organic pure collagen using a critical-sized rodent mandibular defect model. Micro-computed tomographic imaging and histologic staining were used to evaluate new bone formation in vivo. RESULTS: When compared with the beta-tricalcium phosphate and collagen scaffolds, the Col-Ap nanocomposite scaffold exhibited superior regeneration properties characterized by profuse deposition of new bony structures and vascularization at the defect center. Immunohistochemistry showed that the transcription factor osterix and vascular endothelial growth factor receptor 1 were highly expressed in the Col-Ap group. The results indicate that the Col-Ap nanocomposite activates more bone-forming cells and stimulates more vascular tissue ingrowth. Furthermore, the Col-Ap nanocomposite induces extracellular matrix secretion and mineralization of rat bone marrow stem cells. The increased expression of transforming growth factor beta 1 may contribute to the formation of a mineralized extracellular matrix. CONCLUSIONS: The present study lays the foundation for the development of Col-Ap nanocomposite-based bone grafts for future clinical applications in bone regeneration of large periapical lesions after apical curettage or apicoectomy. PMID- 27377440 TI - Microbial Ecosystem Analysis in Root Canal Infections Refractory to Endodontic Treatment. AB - INTRODUCTION: The purpose of this study was to combine multiple displacement amplification and checkerboard DNA-DNA hybridization to qualitatively and quantitatively evaluate the microbiota present in infections refractory to endodontic treatment. METHODS: The subjects of this study were 40 patients presenting with periapical lesions refractory to endodontic treatment. Samples were taken by scraping or filing root canal walls with a #10 K-type hand file. Sample DNA was amplified by multiple displacement amplification, and the levels of 107 bacterial taxa were analyzed by checkerboard DNA-DNA hybridization. The taxa were divided into 3 distinct microbial populations depending on their mean proportion in samples (% DNA probe counts +/- standard error of the mean) as follows: dominant (>=3.0%), subdominant (>1.6%-3.0%), and residual (<=1.6%) populations. The significance of differences was determined using the Mann Whitney test. RESULTS: The taxa present with the highest mean proportions (constituting the dominant population) were Corynebacterium diphtheriae (8.03 +/- 0.98), Porphyromonas gingivalis (5.42 +/- 2.09), Streptococcus sobrinus (5.33 +/- 0.69), and Stenotrophomonas maltophilia (4.72 +/- 1.73). Among the subdominant population were Eubacterium saphenum (3.85 +/- 1.06), Helicobacter pylori (3.16 +/- 0.62), Dialister pneumosintes (3.12 +/- 1.1), Clostridium difficile (2.74 +/- 0.41), Enterobacter agglomerans (2.64 +/- 0.54), Salmonella enterica (2.51 +/- 0.52), Mobiluncus mulieris (2.44 +/- 0.6), and Klebsiella oxytoca (2.32 +/- 0.66). In the population of bacteria present at the lowest mean proportions (the residual population), Bacteroides ureolyticus (0.04 +/- 0.01), Haemophilus influenzae (0.04 +/- 0.02), and Prevotella oris (0.01 +/- 0.01) were found at the lowest mean proportions. Enterococcus faecalis was detected in the residual population (0.52 +/- 0.26). CONCLUSIONS: The microbial climax community in teeth refractory to endodontic treatment not only harbors medically important species but also contains distinct microbial consortia present with different population levels. PMID- 27377441 TI - Muscarinic M1 receptor partially modulates higher sensitivity to cadmium-induced cell death in primary basal forebrain cholinergic neurons: A cholinesterase variants dependent mechanism. AB - Cadmium is a toxic compound reported to produce cognitive dysfunctions, though the mechanisms involved are unknown. In a previous work we described how cadmium blocks cholinergic transmission and induces greater cell death in primary cholinergic neurons from the basal forebrain. It also induces cell death in SN56 cholinergic neurons from the basal forebrain through M1R blockage, alterations in the expression of AChE variants and GSK-3beta, and an increase in Abeta and total and phosphorylated Tau protein levels. It was observed that the silencing or blockage of M1R altered ChAT activity, GSK-3beta, AChE splice variants gene expression, and Abeta and Tau protein formation. Furthermore, AChE-S variants were associated with the same actions modulated by M1R. Accordingly, we hypothesized that cholinergic transmission blockage and higher sensitivity to cadmium-induced cell death of primary basal forebrain cholinergic neurons is mediated by M1R blockage, which triggers this effect through alteration of the expression of AChE variants. To prove this hypothesis, we evaluated, in primary culture from the basal forebrain region, whether M1R silencing induces greater cell death in cholinergic neurons than cadmium does, and whether in SN56 cells M1R mediates the mechanisms described so as to play a part in the cadmium induction of cholinergic transmission blockage and cell death in this cell line through alteration of the expression of AChE variants. Our results prove that M1R silencing by cadmium partially mediates the greater cell death observed on basal forebrain cholinergic neurons. Moreover, all previously described mechanisms for blocking cholinergic transmission and inducing cell death on SN56 cells after cadmium exposure are partially mediated by M1R through the alteration of AChE expression. Thus, our results may explain cognitive dysfunctions observed in cadmium toxicity. PMID- 27377442 TI - Possibilities and limitations of 2DE-based analyses for identifying low-abundant tumor markers in human serum and plasma. AB - Hallmarks of malignancy can be monitored by protein signatures in serum or plasma. The current challenge in cancer research is the identification of clinically reliable protein biomarkers for diagnostic and prognostic purposes. A widely used and powerful technique to screen tumor markers is two-dimensional gel electrophoresis (2DE). This review provides an overview of 2DE functionality with its advantages and drawbacks as well as a current literature overview of gel based cancer biomarker discovery in serum/plasma. In this context, 11 of the 12 studies reviewed here identified at least one of eight classical serum or high abundant proteins (HAPs). Expression levels of those proteins are regulated by a vast variety of different physiological, metabolic and immunological stimuli leading to a questionable application as cancer-specific markers. Misinterpretation of HAPs as tumor markers might be caused by either the experimental setup or the technical and analytical potential in gel-based serum or plasma proteomics to detect low-abundant proteins, or a combination thereof. Additionally, based on currently available technology we propose an optimized experimental workflow to allow detecting cancer-specific protein markers of low abundance in future 2DE studies. PMID- 27377443 TI - Community-acquired Clostridium difficile infections in emergency departments. AB - OBJECTIVE: Clostridium difficile infection (CDI) has become an emerging infectious disease, especially in community settings. Little data is available on its frequency and characteristics in France. We aimed to describe CDI case patients consulting at the emergency department and to compare community-acquired and nosocomial CDIs. PATIENTS AND METHODS: We conducted a multicenter retrospective study over a three-year period of community-acquired and nosocomial CDI case patients seen at the emergency department and compared their characteristics. RESULTS: A total of 2055 patients consulted for diarrhea during the study period and had a stool culture performed: 66 (3.2%) presented with a CDI, of which 28 were community-acquired and 26 were nosocomial. Community acquired CDI patients had a mean age of 57.7years (18-91), with a sex-ratio of 0.65. At least one risk factor was observed in 24 patients (85.7%), of whom 22 (78.6%) had been prescribed a previous antimicrobial treatment. Diabetes mellitus and renal failure were more frequently observed in patients presenting with nosocomial CDI. They required fluid replacement and needed be to re-hospitalized more often than community-acquired patients. CONCLUSION: Community-acquired CDIs in the emergency department account for approximately 1.4% of patients presenting with diarrhea. One risk factor is present in 85.7% of cases. In our study, their presentation and outcome seemed less severe than nosocomial CDIs. PMID- 27377444 TI - Community-acquired pneumonia and positive urinary antigen tests: Factors associated with targeted antibiotic therapy. AB - BACKGROUND: The use of rapid microbiological tests is supported by antimicrobial stewardship policies. Targeted antibiotic therapy (TAT) for community-acquired pneumonia (CAP) with positive urinary antigen test (UAT) has been associated with a favorable impact on outcome. We aimed to determine the factors associated with TAT prescription. PATIENTS AND METHODS: We conducted a retrospective multicenter study including all patients presenting with CAP and positive UAT for Streptococcus pneumoniae or Legionella pneumophila from January 2010 to December 2013. Patients presenting with aspiration pneumonia, coinfection, and neutropenia were excluded. CAP severity was assessed using the Pneumonia Severity Index (PSI). TAT was defined as the administration of amoxicillin for pneumococcal infection and either macrolides or fluoroquinolones (inactive against S. pneumoniae) for Legionella infection. RESULTS: A total of 861 patients were included, including 687 pneumococcal infections and 174 legionellosis from eight facilities and 37 medical departments. TAT was prescribed to 273 patients (32%). Four factors were found independently associated with a lower rate of TAT: a PSI score>=4 (OR 0.37), Hospital A (OR 0.41), hospitalization in the intensive care unit (OR 0.44), and cardiac comorbidities (OR 0.60). Four other factors were associated with a high rate of TAT: positive blood culture for S. pneumoniae (OR 2.32), Hospitals B (OR 2.34), E (OR 2.68), and H (OR 9.32). CONCLUSION: TAT in CAP with positive UAT was related to the hospitals as well as to patient characteristics. PMID- 27377445 TI - Inflammatory reaction to hyaluronic acid: A newly described complication in vocal fold augmentation. AB - OBJECTIVES/HYPOTHESIS: To establish the rate of inflammatory reaction to hyaluronic acid (HA) in vocal fold injection augmentation, determine the most common presenting signs and symptoms, and propose an etiology. STUDY DESIGN: Retrospective chart review. METHODS: Patients injected with HA over a 5-year period were reviewed to identify those who had a postoperative inflammatory reaction. Medical records were reviewed for patient demographic information, subjective complaints, Voice Handicap Index-10 (VHI-10) scores, medical intervention, and resolution time. Videolaryngostroboscopy examinations were also evaluated. RESULTS: A total of 186 patients (245 vocal folds) were injected with HA over a 5-year period, with a postoperative inflammatory reaction rate of 3.8%. The most common complaints in these patients were odynophagia, dysphonia, and dyspnea with vocal fold erythema, edema, and loss of pliability on videolaryngostroboscopy. All patients were treated with corticosteroids. Return of vocal fold vibration ranged from 3 weeks to 26 months, with VHI-10 scores normalizing in 50% of patients. CONCLUSIONS: This reaction may be a form of hypersensitivity related to small amounts of protein linked to HA. Alternatively, extravascular compression from the HA could lead to venous congestion of the vocal fold. The possibility of equipment contamination is also being investigated. Further studies are needed to determine the etiology and best treatment. LEVEL OF EVIDENCE: 4 Laryngoscope, 2016 127:445-449, 2017. PMID- 27377447 TI - Commentary: Police and Suicide Prevention. PMID- 27377448 TI - Organization of care for persons with HIV-infection: a systematic review. AB - The objective of this systematic review was to examine the effectiveness of the organization of care: case management, multidisciplinary care, multi-faceted treatment, hours of service, outreach programs and health information systems on medical, immunological, virological, psychosocial and economic outcomes for persons living with HIV/AIDS. We searched PubMed (MEDLINE) and 10 other electronic databases from 1 January 1980 to April, 2012 for both experimental and controlled observational studies. Thirty-three studies met the inclusion criteria. Eleven studies were randomized controlled trials (RCTs), three of which were conducted in low-middle income settings. Patient characteristics, study design, organization measures and outcomes data were abstracted independently by two reviewers from all studies. A risk of bias tool was applied to RCTs and a separate tool was used to assess the quality of observational studies. This review concludes that case management interventions were most consistently associated with improvements in immunological outcomes but case management demonstrates no clear association with other outcome measures. The same mixed results were also identified for multidisciplinary and multi-faceted care interventions. Eight studies with an outreach intervention were identified and demonstrated improvements or non-inferiority with respect to mortality, receipt of antiretroviral medications, immunological outcomes, improvements in healthcare utilization and lower reported healthcare costs when compared to usual care. Of the interventions examined in this review, sustained in-person case management and outreach interventions were most consistently associated with improved medical and economic outcomes, in particular antiretroviral prescribing, immunological outcomes and healthcare utilization. No firm conclusions can be reached about the impact of any one intervention on patient mortality. PMID- 27377449 TI - Constructing Interfacial Energy Transfer for Photon Up- and Down-Conversion from Lanthanides in a Core-Shell Nanostructure. AB - We report a new mechanistic strategy for controlling and modifying the photon emission of lanthanides in a core-shell nanostructure by using interfacial energy transfer. By taking advantage of this mechanism with Gd(3+) as the energy donor, we have realized efficient up- and down-converted emissions from a series of lanthanide emitters (Eu(3+) , Tb(3+) , Dy(3+) , and Sm(3+) ) in these core-shell nanoparticles, which do not need a migratory host sublattice. Moreover, we have demonstrated that the Gd(3+) -mediated interfacial energy transfer, in contrast to energy migration, is the leading process contributing to the photon emission of lanthanide dopants for the NaGdF4 @NaGdF4 core-shell system. Our finding suggests a new direction for research into better control of energy transfer at the nanometer length scale, which would help to stimulate new concepts for designing and improving photon emission of the lanthanide-based luminescent materials. PMID- 27377450 TI - Effect of cognitive behavioral group therapy for recovery of self-esteem on community-living individuals with mental illness: Non-randomized controlled trial. AB - AIM: The aim of this study was to examine over a 12-month post-intervention period whether the participation of community-living individuals with mental illness in cognitive behavioral group therapy for recovery of self-esteem (CBGTRS) resulted in improved outcomes. METHODS: This was a non-randomized controlled trial. The participants were persons with mental illness who resided in communities in the Chugoku region of Japan. In total, 41 were assigned to an experimental group (CBGTRS intervention, 12 group sessions), and 21 to a control group. Outcome indices (self-esteem, moods, cognition, subjective well-being, psychiatric symptoms) were measured for the experimental group prior to intervention (T0), immediately post-intervention (T1), and at 3 (T2) and 12 (T3) months post-intervention. The control group was measured at the same intervals. RESULTS: For the experimental group, self-esteem scores at T1, T2, and T3 were significantly higher than at T0. Moods and cognition scores remained significantly low until T2. Scores for Inadequate Mental Mastery in the subjective well-being index had not decreased by T3. Confidence in Coping remained significantly high until T2. Psychiatric symptoms scores at T0, T1, T2, and T3 were significantly lower than at T0. The means and standard errors for self-esteem and Inadequate Mental Mastery increased until T3, and those for Tension-Anxiety, Depression-Dejection, and Confusion decreased until T2. CONCLUSION: From within-group trends and between-group differences in self esteem, we conclude that CBGTRS may have a relatively long-term effect on self esteem recovery. T2 is the turning point for moods and cognition; thus, follow-up is needed 3 months following the initial program. PMID- 27377451 TI - Familial mediterranean fever treated with anakinra: A case report. PMID- 27377452 TI - Calcinosis universalis in adult-onset dermatomyositis. PMID- 27377453 TI - A comprehensive review of the clinical approach to pregnancy and systemic lupus erythematosus. AB - Nowadays, most of the young women affected by Systemic Lupus Erythematosus (SLE) can carry out one or more pregnancies thanks to the improvement in treatment and the consequent reduction in morbidity and mortality. Pregnancy outcome in these women has also greatly improved in the last decades. A correct timing for pregnancy (tailored on disease activity and established during a preconception counselling), together with a tight monitoring during the three trimesters and the post-partum period (to timely identify and treat possible obstetric complications or maternal disease flares), as well as the concept of multidisciplinary management, are currently milestones of the management of pregnancy in SLE patients. Nevertheless, the increasing knowledge on the compatibility of drugs with pregnancy has allowed a better treatment of these patients, by choosing medications that control maternal disease activity without harming the foetus. However, particular attention and strict monitoring should be dedicated to SLE pregnant women in particular clinical settings: patients with lupus nephritis and patients with aPL positivity or Antiphospholipid syndrome, who are at higher risk for maternal and foetal complications, but also patients with anti-Ro/SSA and/or anti-La/SSB antibodies, because of the risk of neonatal lupus. A discussion on family planning, as well as counselling on contraception, should be part of the everyday-practice for physicians caring for SLE women during their reproductive age. Another issue is the possible reduction of fertility in these women, that can be due to different reasons. Consequently, the request for assisted reproduction techniques has been increasing in the last years, so that rheumatologists and gynaecologists should be prepared to counsel SLE patients also in this particular setting. PMID- 27377454 TI - IgG4 autoantibodies are inhibitory in the autoimmune disease bullous pemphigoid. AB - The IgG4 subclass of antibodies exhibits unique characteristics that suggest it may function in an immunoregulatory capacity. The inhibitory function of IgG4 has been well documented in allergic disease by the demonstration of IgG4 blocking antibodies, but similar functions have not been explored in autoimmune disease. Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease characterized by autoantibodies directed against BP180 and an inflammatory infiltrate including eosinophils and neutrophils. Animal models have revealed that the NC16A region within BP180 harbors the critical epitopes necessary for autoantibody mediated disease induction. BP180 NC16A-specific IgG belong to the IgG1, IgG3, and IgG4 subclasses. The purpose of this study was to determine effector functions of different IgG subclasses of NC16A-specific autoantibodies in BP. We find that IgG4 anti-NC16A autoantibodies inhibit the binding of IgG1 and IgG3 autoantibodies to the NC16A region. Moreover, IgG4 anti-NC16A blocks IgG1 and IgG3 induced complement fixation, neutrophil infiltration, and blister formation clinically and histologically in a dose-dependent manner following passive transfer to humanized BP180-NC16A mice. These findings highlight the inhibitory role of IgG4 in autoimmune disease and have important implications for the treatment of BP as well as other antibody mediated inflammatory and autoimmune diseases. PMID- 27377455 TI - Mortality in patients with ankylosing spondylitis in Argentina. AB - Some reports describe an increased mortality in patients with ankylosing spondylitis (AS) compared to the general population. The aims of this study were to evaluate the cumulative survival in patients with AS and to establish possible factors associated with mortality. In cross-sectional retrospective study, AS patients were included according to 1984 modified NY criteria, in the 2000-2010 period, the prevalence of mortality was determined by review of medical records, telephone contact, family reports, and death certificates, and it was compared with mortality in Argentina's general population. One hundred twenty-seven patients were studied, 96 (75.6 %) were male, median age 49 years (interquartile range (IQR) 34-60) and median disease duration 8 years (IQR 4-17). During the follow-up period, 9 patients died (7.1 %). The median estimated survival from diagnosis of AS was 39 years (IQR 34-50) and median cumulative survival was 76 years (IQR 74-85). Cardiovascular disease was the most frequent cause of death (5/9 patients). Deceased patients had a mean age and a mean AS disease duration significantly higher than living patients (68.1 +/- 12.4 years vs 46.4 +/- 15.09 years, p = 0.0001 and 33 +/- 13.7 years vs 12 +/- 10.7 years, p = 0.001, respectively), higher frequency of total surgeries [3/5 (60 %) vs 5/105 (4.76 %), p = 0.002] and cauda equina syndrome [3/6 (50 %) vs 2/116 (1.72 %), p = 0.001], respectively. Frequency of mortality in AS patients was higher than the crude mortality rate of Argentina's general population in the same period, with cardiovascular cause being the most frequent one. PMID- 27377456 TI - Development and psychometric analysis of the Patient Perceptions of Patient Empowering Nurse Behaviours Scale (PPPNBS). AB - AIM: To (1) develop and psychometrically test the Patient Perceptions of Patient Empowering Nurse Behaviours Scale, which measures patient perceptions of empowering nurse behaviours during hospitalization; and (2) refine to a shorter, more useful form, for measurement in clinical settings. BACKGROUND: Although patient empowerment has been promoted as a way to engage patients in chronic illness care, there is not a measure reported by patients as recipients of empowering nurse behaviours during hospitalization. DESIGN: Psychometric evaluation of construct and predictive validity, reliability and item reduction. METHOD: Data gathered during hospitalization and six weeks postdischarge between April 2012 - August 2014 were used to determine the validity and reliability of the long and short-form Patient Perceptions of Patient-Empowering Nurse Behaviours Scale in a sample of 395 chronically ill medical and surgical adult patients. RESULTS: The long and short-form Patient Perceptions of Patient Empowering Nurse Behaviours Scale demonstrated strong reliability and convergent validity with pre-discharge 13-item Patient Activation Measure scores. Both forms of the Patient Perceptions of Patient-Empowering Nurse Behaviours Scale predicted postdischarge 13-item Patient Activation Measure scores and the long-form predicted physical health status. Confirmatory factor analysis demonstrated improved model fit for the short-form instrument when compared with the long-form fit. The short-form Patient Perceptions of Patient-Empowering Nurse Behaviours Scale explained 98% of the variance of the long-form Patient Perceptions of Patient-Empowering Nurse Behaviours Scale. CONCLUSION: The results provide evidence supporting reliability and validity of both forms. While the scales measure patient reports and not direct observation of empowering nurse behaviours, incorporating patients' experiences as recipients of care is necessary to validate the contribution of nursing care to patients' engagement in chronic illness management. PMID- 27377457 TI - Bioactivities, isolation and purification methods of polysaccharides from natural products: A review. AB - Polysaccharides play multiple roles and have extensive bioactivities in life process and an immense potential in healthcare, food and cosmetic industries, due to their therapeutic effects and relatively low toxicity. This review describes their major functions involved in antitumor, anti-virus, and anti-inflammatory bioactivities. Due to their enormous structural heterogeneity, the approaches for isolation and purification of polysaccharides are distinct from that of the other macromolecules such as proteins, etc. Yet, to achieve the homogeneity is the initial step for studies of polysaccharide structure, pharmacology, and its structure-activity relationships. According to the experiences accumulated by our lab and the published literatures, this review also introduces the methods widely used in isolation and purification of polysaccharides. PMID- 27377458 TI - Molecular cloning and in silico studies of physiologically significant trehalase from Drosophila melanogaster. AB - Trehalase, a physiologically important glycosidase is known for its crucial role in insect glycometabolism and stress recovery. The present study describes the molecular cloning of a gene fragment, encoding the catalytically active trehalase from Drosophila melanogaster (DmTre) and its heterologous expression in Escherichia coli. The 1275bp gene was overexpressed in two different vectors viz., pET28a and pCOLD TF and investigated for variable soluble expression, purification and activity of the recombinant enzyme with optimum pH and temperature of enzyme as 6 and 55 degrees C, respectively. The sequence was characterized in silico by subjecting it to homology search, multiple sequence alignment and phylogenetic tree construction revealing its identity to other trehalases which belong to glycoside hydrolase family 37. The deduced amino acid sequence and modeled 3D structure of DmTre possessed all features of trehalase superfamily, including signature motifs and catalytic domain. The active site pocket of recombinant DmTre was compared with the crystal structure of E. coli trehalase identifying Glu424 and Asp226 as the putative catalytic residues. Additionally, enzyme-substrate docking suggests possible involvement of other residues in the catalysis along with Asp226. The present study holds significance in understanding the structural aspects of Drosophila trehalase in spite of unavailabilty of eukaryotic trehalase crystal structure. PMID- 27377459 TI - A mini-review of chemical and biological properties of polysaccharides from Momordica charantia. AB - Recently, isolation and characterization of bioactive polysaccharides from natural resources have attracted increasing interest. Momordica charantia L. (M. charantia), belongs to the Curcubitaceae family, which is widely distributed in the tropical and subtropical regions of the world, and has been used as herbal medicine and a vegetable for thousands of years. M. charantia polysaccharides, as major active ingredients of M. charantia, have attracted a great deal of attention because of their various biological activities, such as antitumor, immunomodulation, antioxidant, anti-diabetes, radioprotection, and hepatoprotection. The present review provides the most complete summary of the research progress on the polysaccharides isolated from M. charantia, including the extraction, separation, physical-chemical properties, structural characteristics, and bioactivities during the last ten years. This review also provides a foundation for the further development and application in the field of M. charantia polysaccharides. PMID- 27377460 TI - Inhibitory effect on HT-29 colon cancer cells of a water-soluble polysaccharide obtained from highland barley. AB - A water-soluble polysaccharide (BP-1) was obtained from highland barley (Hordeum vulgare L.) by hot water extraction and purification of sepharose column chromatography. BP-1 had an average molecular weight of about 6.7*104Da and was composed of glucose (Glc), xylose (Xyl), arabinose (Ara) and rhamnose (Rha) with a relative molar ratio of 8.82:1.92:1.50:1.00. It was found that BP-1 inhibited proliferation of human colon cancer cells (HT-29) in a time- and dose-dependent manner with half maximal inhibitory concentration at 48h of 48.18MUg/mL. Western blotting results showed that BP-1 enhanced the phosphorylation of c-Jun N terminal kinase (JNK), processes associated with the reactive oxygen species (ROS) formation and inhibited nuclear factor-kappaB (NF-kappaB) translocation from cytoplasm into nucleus. Meanwhile, the BP-1-induced apoptosis was related to the regulation of apoptosis-associated proteins, such as B-cell lymphoma-2 (Bcl 2), release of cytochrome C from mitochondria to cytoplasm and activation of caspase-8 and caspase-9. These results suggest that BP-1-induced HT-29 apoptosis through ROS-JNK and NF-kappaB-mediated caspase pathways. PMID- 27377461 TI - Isolation and characterisation of a novel alpha-amylase from the extreme haloarchaeon Haloterrigena turkmenica. AB - An extracellular halophilic alpha-amylase (AmyA) was produced by the haloarchaeon Haloterrigena turkmenica grown in medium enriched with 0.2% (w/v) starch. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and size exclusion chromatography (SEC) analyses showed a major band at 66.0kDa and a peak of 54.0kDa, respectively. Analysis of tryptic fragments of the protein present in the major SDS-PAGE band by nano-LC-ESI-MS/MS led to identification of the alpha amylase catalytic region, encoded by the htur2110 gene, as the protein possessing the described activity. Optimal values for activity were 55 degrees C, pH 8.5 and 2M NaCl, and high thermostability was showed at 55 degrees C and 3M NaCl. AmyA activity was enhanced by Triton X-100 and was not influenced by n-hexane and chloroform. Starch hydrolysis produced different oligomers with maltose as the smallest end-product. The efficiency of AmyA in degrading starch contained in agronomic residues was tested in grape cane chosen as model substrate. Preliminary results showed that starch was degraded making the enzyme a potential candidate for utilization of agro-industrial waste in fuel and chemicals production. AmyA is one of the few investigated amylases produced by haloarchaea, and the first alpha-amylase described among microorganisms belonging to the genus Haloterrigena. PMID- 27377462 TI - Structural and thermodynamic characterisation of L94F mutant of horse cytochrome c. AB - Mammalian mitochondrial cytochromes c (cyts c) has a conserved Leu94 which is replaced by valine/isoleucine in some lower eukaryotes and prokaryotes. It is expected that nature substituted Leu94 with Val/Ile, for they have similar van der Waals volume and hydrophobicity with a difference in side chain branching only. Reports also suggested the presence of phenylalanine at position 94, which leads to questions: (i) How bulky aromatic amino acid residue fitted at position 94 in cyt c family proteins? (ii) What is the effect of L94F mutation on protein stability and folding? Here, we selected horse cyt-c as a model to answer the second question. We generated L94F mutant of horse cytochrome c and subsequently characterised using far-UV, near-UV and Soret circular dichroism, absorbance, intrinsic and extrinsic ANS (8-anilino-1-napthalenesulfonic acid) fluorescence and dynamic light scattering measurements. We observed that this mutation affects the native state and arrests the protein folding at the molten globule state. Thermal stability of L94F mutant is also measured by spectroscopic techniques and differential scanning calorimetry. The midpoint of thermal denaturation of L94F mutant is 17 degrees C less than wild type. Molecular dynamics simulation study also supports our in vitro observation that this mutant has stable backbone conformation. PMID- 27377464 TI - In Memoriam Rudy Vanmaele (1945-2010). PMID- 27377465 TI - Novel stereoselective bufadienolides reveal new insights into the requirements for Na(+), K(+)-ATPase inhibition by cardiotonic steroids. AB - Cardiotonic steroids (CTS) are clinically important drugs for the treatment of heart failure owing to their potent inhibition of cardiac Na(+), K(+)-ATPase (NKA). Bufadienolides constitute one of the two major classes of CTS, but little is known about how they interact with NKA. We report a remarkable stereoselectivity of NKA inhibition by native 3beta-hydroxy bufalin over the 3alpha-isomer, yet replacing the 3beta-hydroxy group with larger polar groups in the same configuration enhances inhibitory potency. Binding of the two (13)C labelled glycosyl diastereomers to NKA were studied by solid-state NMR (SSNMR), which revealed interactions of the glucose group of the 3beta- derivative with the inhibitory site, but much weaker interactions of the 3alpha- derivative with the enzyme. Molecular docking simulations suggest that the polar 3beta-groups are closer to the hydrophilic amino acid residues in the entrance of the ligand binding pocket than those with alpha-configuration. These first insights into the stereoselective inhibition of NKA by bufadienolides highlight the important role of the hydrophilic moieties at C3 for binding, and may explain why only 3beta hydroxylated bufadienolides are present as a toxic chemical defence in toad venom. PMID- 27377466 TI - Online Health Information-Seeking Behavior and Confidence in Filling Out Online Forms Among Latinos: A Cross-Sectional Analysis of the California Health Interview Survey, 2011-2012. AB - BACKGROUND: Health information is increasingly being disseminated online, but there is a knowledge gap between Latinos and non-Hispanic whites, particularly those whose English language proficiency is poor, in terms both of online health information-seeking behavior and computer literacy skills. This knowledge gap may also exist between US- and foreign-born Latinos. OBJECTIVE: The specific aim of this study was to examine Internet use, online health information-seeking behavior, and confidence in filling out online forms among Latinos, particularly as it relates to health-risk behaviors. We then stratified our sample by nativity. METHODS: We used the adult population file of the 2011-2012 California Health Interview Survey, analyzing Internet use, online health information seeking behavior, and confidence in filling out online forms using binary logistic regression among Latinos and whites (N=27,289), Latinos (n=9506), and Latinos who use the Internet (n=6037). RESULTS: Foreign-born Latinos (OR 0.71, 95% CI 0.58-0.88, P=.002) have lower odds of engaging in online health information-seeking behavior, and higher odds (OR 2.90, 95% CI 2.07-4.06, P<.001) of reporting a lack of confidence in filling out online forms compared to US-born Latinos. Correlates of online health information-seeking behavior and form confidence varied by nativity. CONCLUSIONS: Latinos, particularly foreign-born individuals, are at an increased risk of being left behind as the move to increase online content delivery and care expands. As online health information dissemination and online health portals become more popular, the impact of these sites on Latino gaps in coverage and care should be considered. PMID- 27377463 TI - A Frameshift in CSF2RB Predominant Among Ashkenazi Jews Increases Risk for Crohn's Disease and Reduces Monocyte Signaling via GM-CSF. AB - BACKGROUND & AIMS: Crohn's disease (CD) has the highest prevalence in Ashkenazi Jewish populations. We sought to identify rare, CD-associated frameshift variants of high functional and statistical effects. METHODS: We performed exome sequencing and array-based genotype analyses of 1477 Ashkenazi Jewish individuals with CD and 2614 Ashkenazi Jewish individuals without CD (controls). To validate our findings, we performed genotype analyses of an additional 1515 CD cases and 7052 controls for frameshift mutations in the colony-stimulating factor 2 receptor beta common subunit gene (CSF2RB). Intestinal tissues and blood samples were collected from patients with CD; lamina propria leukocytes were isolated and expression of CSF2RB and granulocyte-macrophage colony-stimulating factor responsive cells were defined by adenomatous polyposis coli (APC) time-of-flight mass cytometry (CyTOF analysis). Variants of CSF2RB were transfected into HEK293 cells and the expression and functions of gene products were compared. RESULTS: In the discovery cohort, we associated CD with a frameshift mutation in CSF2RB (P = 8.52 * 10(-4)); the finding was validated in the replication cohort (combined P = 3.42 * 10(-6)). Incubation of intestinal lamina propria leukocytes with granulocyte-macrophage colony-stimulating factor resulted in high levels of phosphorylation of signal transducer and activator of transcription (STAT5) and lesser increases in phosphorylation of extracellular signal-regulated kinase and AK straining transforming (AKT). Cells co-transfected with full-length and mutant forms of CSF2RB had reduced pSTAT5 after stimulation with granulocyte-macrophage colony-stimulating factor, compared with cells transfected with control CSF2RB, indicating a dominant-negative effect of the mutant gene. Monocytes from patients with CD who were heterozygous for the frameshift mutation (6% of CD cases analyzed) had reduced responses to granulocyte-macrophage colony-stimulating factor and markedly decreased activity of aldehyde dehydrogenase; activity of this enzyme has been associated with immune tolerance. CONCLUSIONS: In a genetic analysis of Ashkenazi Jewish individuals, we associated CD with a frameshift mutation in CSF2RB. Intestinal monocytes from carriers of this mutation had reduced responses to granulocyte-macrophage colony-stimulating factor, providing an additional mechanism for alterations to the innate immune response in individuals with CD. PMID- 27377468 TI - Different magnetic responses observed in Co, Co and Co-based MOFs. AB - Four magnetic MOFs with anisotropic Co(II) ions, {[Co5(H2O)2(MU3 OH)2(atz)2(stp)2].1.5H2O}n (1), {[Co5(H2O)2(MU3-OH)2(trz)2(stp)2].1.3H2O}n (2), {[Co5(H2O)6(MU3-OH)2(trz)2(stp)2].2.5CH3OH}n (3) and {[Co3(H2O)4(Hdatrz)2(stp)2].3H2O}n (4) (stp(3-) = 2-sulfoterephthalate, trz(-) = 1,2,4-triazolate, atz(-) = 3-amino-1,2,4-triazolate and Hdatrz = 3,5-diamino 1,2,4-triazole) were solvothermally isolated by varying the substituent groups appended on the N-heterocyclic triazole and structurally and magnetically characterized. Structural analyses indicate that the former two complexes are crystallographically isostructural, exhibiting pillared-layer frameworks with mixed triazolyl and carboxylate extended Co + Co layers supported by rigid stp(3 ) connectors. Complex 3 is built from butterfly-shaped Co cluster-based layers, which are interconnected with single cobalt(ii) octahedra by ditopic stp(3-) bridges. By contrast, complex 4 consists of linear {Co3(MU-N1,N4-Hdatrz)2} subunits, which are extended by 3-connected stp(3-) linkers into a stable 3D framework. Magnetically, 1 exhibits ferromagnetic ordering below 2.7 K due to the well-organized alignment of the non-compensated resultant moment from octahedra and tetrahedral cobalt(ii) carriers, while 3 is in a non-zero paramagnetic state above 2.0 K resulting from the coexistence of intermetallic ferromagnetic and antiferromagnetic interactions. The magnetic competition between weak inter subunit antiferromagnetic interactions and the external magnetic field makes 4 behave as a field-induced metamagnet with a critical field of 27.5 kOe. These interesting magnetostructural results suggest that the anisotropy of the moment carrier and the interlayer/intersubunit separations significantly dominate the magnetic responses in extended MOFs, providing an informative platform for the further development of interesting magnetic materials, both of academic and industrial interest. PMID- 27377467 TI - Secondary hyperalgesia is mediated by heat-insensitive A-fibre nociceptors. AB - KEY POINTS: It is believed that secondary hyperalgesia (the increased sensitivity to mechanical nociceptive stimuli that develops after cutaneous tissue injury in the surrounding uninjured skin) is mediated by a subclass of nociceptors: the slowly adapting A-fibre mechano-heat nociceptors (AMH-type I). Here we tested this hypothesis. By using intense long-lasting heat stimuli, which are known to activate these slowly adapting AMH-type I nociceptors, we show that the perceived intensity elicited by these stimuli is not increased in the area of secondary hyperalgesia. Moreover, we show that during an A-fibre nerve conduction block the perception elicited by the long-lasting heat stimuli is significantly reduced in a time window that matches the response profile of the AMH-type I nociceptors. AMH-type I nociceptors contribute to the perception of sustained heat, but they do not mediate secondary hyperalgesia. Therefore, we propose that secondary hyperalgesia is mediated by high threshold mechanoreceptors. ABSTRACT: Secondary hyperalgesia refers to the increase in sensitivity to mechanical nociceptive stimuli delivered outside the area of tissue injury. Previous studies have suggested that secondary hyperalgesia is mediated by a specific class of myelinated nociceptors: slowly adapting A-fibre mechano- and heat-sensitive (AMH) type I nociceptors. Here, we tested this hypothesis by examining whether long lasting heat stimuli, which are known to activate AMH-type I nociceptors, elicit enhanced responses when delivered to the area of secondary hyperalgesia induced by high frequency electrical stimulation of the skin (HFS). Before and 20 min after HFS, sustained 30 s radiant heat stimuli were delivered to the area of increased mechanical pinprick sensitivity while participants continuously rated intensity of perception using an online visual analog scale (0-100 mm). After HFS, no significant enhancement of heat perception was observed in the area of increased pinprick sensitivity. To establish that myelinated nociceptors actually contribute to the perception of sustained heat, we conducted a second experiment in which sustained heat stimuli were presented before and during an A-fibre nerve conduction block, achieved by applying a rubber band with weights which compresses the superficial radial nerve against the radius. During the block, heat perception was significantly reduced 17-33 s after the onset of the heat stimulus (before: mean = 53 mm, during: mean = 31 mm; P = 0.03), matching the response profile of AMH-type I nociceptors. These results support the notion that AMH-type I nociceptors contribute to the perception of sustained heat, but also show that these afferents do not mediate secondary hyperalgesia. PMID- 27377469 TI - CD24 is a genetic modifier for risk and progression of prostate cancer. AB - CD24 plays an oncogenic role in the onset and progression of various human cancers, including prostate cancer. In the present study, we identified two linkage disequilibrium blocks with four recombination hotspot motifs in human CD24 locus. To elucidate whether genetic variants of CD24 are associated with susceptibility to prostate cancer and its disease status, we conducted a case control association study with two P170 C/T and P-534 A/C polymorphisms of CD24 in 590 patients with prostate cancer and 590 healthy controls. A significant increased risk of prostate cancer was found in men with the P170T/T genotype over the P170C/C genotype (odd ratio = 1.74, 95% confidence interval = 1.16-2.63, P = 0.008), and in men with the P-534C/C genotype over the P-534A/A genotype (odd ratio = 1.47, 95% CI = 1.18-2.26, P = 0.003). Cochran-Armitage trend analysis showed that the P170T allele was significantly correlated with an increased risk of prostate cancer progression (P = 0.029, trend between genotypes and stages) and this observation was also validated in an independent sample cohort. Next, we found that tumors with P170T or P-534C alleles had more twofold increased protein expressions of CD24 as compared to those with P170C or P-534A alleles, respectively. Likewise, tumors with a combination of P170T/T and P-534C/C genotypes were associated with a high mRNA level of CD24. Our data suggest a significant association of CD24 genetic variants with prostate cancer onset and progression, which provides new insight into molecular genetics of prostate cancer; however, these findings need to be validated in multiple independent cohorts. (c) 2016 Wiley Periodicals, Inc. PMID- 27377471 TI - Compound-Specific Isotope Analyses to Assess TCE Biodegradation in a Fractured Dolomitic Aquifer. AB - The potential for trichloroethene (TCE) biodegradation in a fractured dolomite aquifer at a former chemical disposal site in Smithville, Ontario, Canada, is assessed using chemical analysis and TCE and cis-DCE compound-specific isotope analysis of carbon and chlorine collected over a 16-month period. Groundwater redox conditions change from suboxic to much more reducing environments within and around the plume, indicating that oxidation of organic contaminants and degradation products is occurring at the study site. TCE and cis-DCE were observed in 13 of 14 wells sampled. VC, ethene, and/or ethane were also observed in ten wells, indicating that partial/full dechlorination has occurred. Chlorine isotopic values (delta37 Cl) range between 1.39 to 4.690/00 SMOC for TCE, and 3.57 to 13.860/00 SMOC for cis-DCE. Carbon isotopic values range between -28.9 and -20.70/00 VPDB for TCE, and -26.5 and -11.80/00 VPDB for cis-DCE. In most wells, isotopic values remained steady over the 15-month study. Isotopic enrichment from TCE to cis-DCE varied between 0 and 130/00 for carbon and 1 and 40/00 for chlorine. Calculated chlorine-carbon isotopic enrichment ratios (epsilonCl /epsilonC ) were 0.18 for TCE and 0.69 for cis-DCE. Combined, isotopic and chemical data indicate very little dechlorination is occurring near the source zone, but suggest bacterially mediated degradation is occurring closer to the edges of the plume. PMID- 27377470 TI - Risk of second primary malignancies among cancer survivors in the United States, 1992 through 2008. AB - BACKGROUND: In the current study, the authors attempted to describe the incidence, most common sites, and mortality of second primary malignancies among survivors of common cancers. METHODS: The authors identified patients aged >=18 years who were diagnosed with a primary malignancy from the 10 most common cancer sites (prostate, breast, lung, colon, rectum, bladder, uterus, kidney, melanoma, and non-Hodgkin lymphoma) between 1992 and 2008 from Surveillance, Epidemiology, and End Results data. Factors associated with the incidence of second primary malignancies were explored using bivariable and multivariable models, and mortality attributable to first and second primary malignancies was examined. RESULTS: A cohort of 2,116,163 patients was identified, 170,865 of whom (8.1%) developed a second primary malignancy. Survivors of bladder cancer had the highest risk of developing a second cancer. In a multivariable model controlling for age, race, tumor grade, stage of disease, marital status, educational level, and income, a history of non-Hodgkin lymphoma (hazard ratios of 2.70 and 2.88, respectively, for men and women) and bladder cancer (hazard ratios of 1.88 and 1.66, respectively, for men and women) predicted the highest risk of developing a second cancer. For patients with 2 incident cancers, 13% died of their initial cancer, but greater than one-half (55%) died of their second primary malignancy. Lung cancer was the cause of death in 12% of patients with 2 incident cancers. CONCLUSIONS: Nearly 1 in 12 patients diagnosed with a common cancer developed a second malignancy, the most common of which was lung cancer. Greater than one half of patients with 2 incident cancers died of their secondary malignancy. The findings from the current study may inform care strategies among cancer survivors. Cancer 2016;122:3075-3086. (c) 2016 American Cancer Society. PMID- 27377472 TI - Local Time-Dependent Charging in a Perovskite Solar Cell. AB - Efficient charge extraction within solar cells explicitly depends on the optimization of the internal interfaces. Potential barriers, unbalanced charge extraction, and interfacial trap states can prevent cells from reaching high power conversion efficiencies. In the case of perovskite solar cells, slow processes happening on time scales of seconds cause hysteresis in the current voltage characteristics. In this work, we localized and investigated these slow processes using frequency-modulation Kelvin probe force microscopy (FM-KPFM) on cross sections of planar methylammonium lead iodide (MAPI) perovskite solar cells. FM-KPFM can map the charge density distribution and its dynamics at internal interfaces. Upon illumination, space charge layers formed at the interfaces of the selective contacts with the MAPI layer within several seconds. We observed distinct differences in the charging dynamics at the interfaces of MAPI with adjacent layers. Our results indicate that more than one process is involved in hysteresis. This finding is in agreement with recent simulation studies claiming that a combination of ion migration and interfacial trap states causes the hysteresis in perovskite solar cells. Such differences in the charging rates at different interfaces cannot be separated by conventional device measurements. PMID- 27377473 TI - 217th ENMC International Workshop: RYR1-related myopathies, Naarden, The Netherlands, 29-31 January 2016. PMID- 27377474 TI - New ways to promote public health: lessons from the international Ice Bucket Challenge. PMID- 27377475 TI - Three novel Cu6S6 cluster-based coordination compounds: synthesis, framework modulation and the sensing of small molecules and Fe(3+) ions. AB - Three novel Cu6S6 cluster-based coordination compounds formulated as [Cu(mpymt)3]2 (1), {(CuBr4)[Cu(mpymt)6]}n (2), and {(CuI6)[Cu(mpymt)6]}n (3) (Hmpymt = 4-methylpyrimidine-2-thione), have been synthesized under solvothermal conditions and characterized by elemental analysis, infrared (IR) spectroscopy, thermal gravimetric analysis, powder X-ray diffraction and single-crystal X-ray diffraction. Structural analysis reveals that compound 1 shows a distorted octahedral core of six copper atoms (Cu6S6) constructed from four alpha and two beta type N[double bond, length as m-dash]C-SH parts from six mpymt(-) anions. Compound 2 displays an interesting 3D framework constructed from Cu6S6 and Cu4Br4 Cu(i) clusters simultaneously, interestingly, six mpymt(-) with alpha type N[double bond, length as m-dash]C-SH parts are involved in the formation of Cu6S6. Compound 3 displays an infinite 1D framework constructed from Cu6S6 and Cu6I6 Cu(i) clusters, notably, four alpha and two beta type N[double bond, length as m-dash]C-SH parts are involved in the formation of the Cu6S6 cluster, however, only mpymt(-) ligands containing alpha type N[double bond, length as m-dash]C-SH parts form the bridged Cu6I6 cluster. The experimental results reveal that halogen ions finely modulate the structural features of compounds 1-3. The fluorescent properties of compounds 1-3 in the solid state and in various solvent emulsions were investigated in detail, the results of which indicate that compounds 1-3 are all highly sensitive naked eye colorimetric sensors for NB, 2 NT and Fe(3+) (NB = nitrobenzene and 2-NT = 2-nitrotoluene). PMID- 27377477 TI - Extending the Dynamic Range in Metabolomics Experiments by Automatic Correction of Peaks Exceeding the Detection Limit. AB - Metabolomics, the analysis of potentially all small molecules within a biological system, has become a valuable tool for biomarker identification and the elucidation of biological processes. While metabolites are often present in complex mixtures at extremely different concentrations, the dynamic range of available analytical methods to capture this variance is generally limited. Here, we show that gas chromatography coupled to atmospheric pressure chemical ionization mass spectrometry (GC-APCI-MS), a state of the art analytical technology applied in metabolomics analyses, shows an average linear range (LR) of 2.39 orders of magnitude for a set of 62 metabolites from a representative compound mixture. We further developed a computational tool to extend this dynamic range on average by more than 1 order of magnitude, demonstrated with a dilution series of the compound mixture, using robust and automatic reconstruction of intensity values exceeding the detection limit. The tool is freely available as an R package (CorrectOverloadedPeaks) from CRAN ( https://cran.r-project.org/ ) and can be incorporated in a metabolomics data processing pipeline facilitating large screening assays. PMID- 27377476 TI - Tolerance to oxidative stress is required for maximal xylem colonization by the xylem-limited bacterial phytopathogen, Xylella fastidiosa. AB - Bacterial plant pathogens often encounter reactive oxygen species (ROS) during host invasion. In foliar bacterial pathogens, multiple regulatory proteins are involved in the sensing of oxidative stress and the activation of the expression of antioxidant genes. However, it is unclear whether xylem-limited bacteria, such as Xylella fastidiosa, experience oxidative stress during the colonization of plants. Examination of the X. fastidiosa genome uncovered only one homologue of oxidative stress regulatory proteins, OxyR. Here, a knockout mutation in the X. fastidiosa oxyR gene was constructed; the resulting strain was significantly more sensitive to hydrogen peroxide (H2 O2 ) relative to the wild-type. In addition, during early stages of grapevine infection, the survival rate was 1000-fold lower for the oxyR mutant than for the wild-type. This supports the hypothesis that grapevine xylem represents an oxidative environment and that X. fastidiosa must overcome this challenge to achieve maximal xylem colonization. Finally, the oxyR mutant exhibited reduced surface attachment and cell-cell aggregation and was defective in biofilm maturation, suggesting that ROS could be a potential environmental cue stimulating biofilm development during the early stages of host colonization. PMID- 27377478 TI - [Zika virus: chronicle of an "unexpected" pandemic]. PMID- 27377479 TI - Rapid identification of the NAT2 genotype in tuberculosis patients by multicolor melting curve analysis. AB - AIM: NAT2 genotype is an indicator for isoniazid dosage adjusting for tuberculosis treatment. Multicolor melting curve analysis (MMCA) was evaluated as a potential method for NAT2 genotyping. MATERIALS & METHODS: 352 blood samples were analyzed by MMCA kit (Zeesan Biotech Co., Xiamen, China) targeting NAT2 SNPs at T341C, C481T, G590A and G857A, and direct sequencing was used as control. RESULTS: The sensitivity, specificity and accuracy of the MMCA assay for rapid NAT2 genotype detection were 97.9, 99.6 and 99.1% respectively, whereas for intermediate genotypes the values were 99.5, 98.7 and 99.1%, respectively, and for slow genotypes the values were 100% for the three aspects. The 24 saliva and blood for the control samples were also successfully analyzed using the MMCA assay, both produced uniform outcomes. CONCLUSION: The MMCA assay described in our study is very promising for the efficient determination of NAT2 genotype, and can facilitate the personalized dosing of isoniazid. PMID- 27377480 TI - A short and modular approach towards 3,5-disubstituted indolizidine alkaloids. AB - 3,5-Dialkyl indolizidines have been prepared in four linear steps from commercially available starting materials. The sequence involves two direct alpha functionalization steps and a subsequent reductive amination and provides diastereoselective access to both C-3 epimers of the 5,9-trans-substituted indolizines. The naturally occurring indolizidines 195B and 223AB have been synthesized using this methodology. PMID- 27377481 TI - Ultrabroad Photoluminescence and Electroluminescence at New Wavelengths from Doped Organometal Halide Perovskites. AB - Doping of semiconductors by introducing foreign atoms enables their widespread applications in microelectronics and optoelectronics. We show that this strategy can be applied to direct bandgap lead-halide perovskites, leading to the realization of ultrawide photoluminescence (PL) at new wavelengths enabled by doping bismuth (Bi) into lead-halide perovskites. Structural and photophysical characterization reveals that the PL stems from one class of Bi doping-induced optically active center, which is attributed to distorted [PbI6] units coupled with spatially localized bipolarons. Additionally, we find that compositional engineering of these semiconductors can be employed as an additional way to rationally tune the PL properties of doped perovskites. Finally, we accomplished the electroluminescence at cryogenic temperatures by using this system as an emissive layer, marking the first electrically driven devices using Bi-doped photonic materials. Our results suggest that low-cost, earth-abundant, solution processable Bi-doped perovskite semiconductors could be promising candidate materials for developing optical sources operating at new wavelengths. PMID- 27377482 TI - Targeting tumor hypoxia with the epigenetic anticancer agent, RRx-001: a superagonist of nitric oxide generation. AB - This study reveals a novel interaction between deoxyhemoglobin, nitrite and the non-toxic compound, RRx-001, to generate supraphysiologic levels of nitric oxide (NO) in blood. We characterize the nitrite reductase activity of deoxyhemoglobin, which in the presence of bound RRx-001 reduces nitrite at a much faster rate, leading to markedly increased NO generation. These data expand on the paradigm that hemoglobin generates NO via nitrite reduction during hypoxia and ischemia when nitric oxide synthase (NOS) function is limited. Here, we demonstrate that RRx-001 greatly enhances NO generation from nitrite reduction. RRx-001 is thus the first example of a functional superagonist for nitrite reductase. We hypothesize that physiologically this reaction releases the potentially cytotoxic effector NO selectively in hypoxic tumor regions. It may be that a binary NO-H2O2 trigger is indirectly responsible for the observed tumoricidal activity of RRx 001 since NO is known to inhibit mitochondrial respiration. PMID- 27377483 TI - The photoprotective effects of 2-benzoyl-3-phenylquinoxaline 1,4-dioxide against UVB-induced damage in HaCaT cells. AB - With the increasing levels of atmospheric ozone depletion, there has been much concern about the causal effects of high levels of ultraviolet radiation reaching the Earth's surface on skin cancer. This has led to growing interest in identifying new active ingredients for use in commercial sunscreens. In our study, the chemical compound 2-benzoyl-3-phenylquinoxaline 1,4-dioxide (BPQ) prepared by the Beirut reaction was tested for its ability to protect a human keratinocyte cell line (HaCaT) against ultraviolet B radiation (280-315 nm). We show that BPQ exhibited strong absorbance in the UVB range, with an overall absorption spectrum very similar to that of Padimate-O, a well-known active ingredient used in commercial sunscreens. HaCaT cells, which were irradiated with UVB in the presence of multiple doses of BPQ, exhibited, in a dose-dependent fashion, a significantly higher viability and lower oxidative stress levels than cells irradiated in the absence of drug. Our results show that BPQ is a potential photoprotective drug that holds great promise for use as an active ingredient in commercial sunscreens. PMID- 27377484 TI - Drug Addiction: A Global Challenge. PMID- 27377485 TI - Current Status of Substance Abuse in East Asia and Therapeutic Prospects. AB - The abuse of drugs, including opioids and stimulants, is a major public health problem worldwide, including in East Asia. Nonetheless, there are no pharmacological treatments for many psychiatric or neurological symptoms associated with that abuse. Abused drugs exert several detrimental effects on structural plasticity in brain regions associated with reward circuits. Understanding the molecular mechanisms that underlie this structural plasticity in brain neurons will aid in the development of novel therapeutic drugs for substance abuse. In this review, we discuss recent topics in substance abuse in East Asia and the therapeutic drugs available. Finally, we discuss potential therapeutic signalling pathways involved in long-term changes to structural plasticity in the brain after repeated administration of opioids and stimulants. PMID- 27377486 TI - Developing Treatments for Stimulant Abuse: A Brief Overview. AB - The abuse of stimulants such as cocaine, amphetamine, and methamphetamine is a huge problem in many parts of the world. Abuse of these drugs does not ruin just the user's life, but also adversely affects those around them. Despite many years of research, there are no approved medications for stimulant dependence, and treatment is focused on psychotherapy and abstinence. Over the last 10 to 20 years, there have been some major changes in approach to medication development for stimulant dependence. These include assessing ligands for non-dopaminergic sites, atypical dopamine transporter ligands, blocking long-term potentiation and / or memory reconsolidation, vaccines against the stimulant, and molecular approaches including pharmacogenomics and gene silencing. Also included in this overview are non-drug treatments such as deep brain stimulation and psychosurgery. This overview highlights recent preclinical and clinical studies of treatment development for stimulant dependence. PMID- 27377488 TI - Acupuncture for Detoxification in Treatment of Opioid Addiction. AB - Opioid is a popular drug of abuse and addiction. We evaluated acupuncture as a non-pharmacological treatment with a focus on managing withdrawal symptoms. Electrical stimulation at a low frequency (2 Hz) accelerates endorphin and encephalin production. High-frequency stimulation (100 Hz) up-regulates the dynorphin level that in turn suppresses withdrawal at the spinal level. The effect of 100-Hz electroacupuncture may be associated with brain-derived neurotrophic factor activation at the ventral tegmental area, down-regulation of cAMP response element-binding protein, and enhanced dynorphin synthesis in the spinal cord, periaqueductal grey, and hypothalamus. Clinical trials of acupuncture for the management of different withdrawal symptoms were reviewed. The potential of acupuncture to allay opioid-associated depression and anxiety, and its possible use as an adjuvant treatment were evident. A lack of effect was indicated for opioid craving. Most studies were hampered by inadequate reporting details and heterogeneity, thus future well-designed studies are needed to confirm the efficacy of acupuncture in opioid addiction treatment. PMID- 27377487 TI - Permissive Attitude Towards Drug Use, Life Satisfaction, and Continuous Drug Use Among Psychoactive Drug Users in Hong Kong. AB - OBJECTIVES: To examine the effects of a permissive attitude towards regular and occasional drug use, life satisfaction, self-esteem, depression, and other psychosocial variables in the drug use of psychoactive drug users. Psychosocial factors that might affect a permissive attitude towards regular / occasional drug use and life satisfaction were further explored. METHODS: We analysed data of a sample of psychoactive drug users from a longitudinal survey of psychoactive drug abusers in Hong Kong who were interviewed at 6 time points at 6-month intervals between January 2009 and December 2011. Data of the second to the sixth time points were stacked into an individual time point structure. Random-effects probit regression analysis was performed to estimate the relative contribution of the independent variables to the binary dependent variable of drug use in the last 30 days. RESULTS: A permissive attitude towards drug use, life satisfaction, and depression at the concurrent time point, and self-esteem at the previous time point had direct effects on drug use in the last 30 days. Interestingly, permissiveness to occasional drug use was a stronger predictor of drug use than permissiveness to regular drug use. These 2 permissive attitude variables were affected by the belief that doing extreme things shows the vitality of young people (at concurrent time point), life satisfaction (at concurrent time point), and self-esteem (at concurrent and previous time points). Life satisfaction was affected by sense of uncertainty about the future (at concurrent time point), self-esteem (at concurrent time point), depression (at both concurrent and previous time points), and being stricken by stressful events (at previous time point). CONCLUSIONS: A number of psychosocial factors could affect the continuation or discontinuation of drug use, as well as the permissive attitude towards regular and occasional drug use, and life satisfaction. Implications of the findings for prevention and intervention work targeted at psychoactive drug users are discussed. PMID- 27377489 TI - Depression and Associated Factors in Patients with Type 2 Diabetes Mellitus. AB - OBJECTIVES: To determine the prevalence of major depressive disorder and its association with socio-demographic and clinical factors in patients with type 2 diabetes mellitus. METHODS: This was a cross-sectional study of patients with type 2 diabetes mellitus who attended the hospital-based primary care clinics at the University Malaya Medical Centre, Kuala Lumpur, Malaysia. The patients were interviewed using the Mini-International Neuropsychiatric Interview to diagnose depression based on the DSM-IV criteria. The socio-demographic and clinical data were obtained by interviewing the patients and subsequently verified against their respective case notes. RESULTS: A total of 204 patients were recruited. The prevalence of major depressive disorder was 15.7%. Major depressive disorder was significantly associated with younger age of patients (mean +/- standard deviation, 57.8 +/- 15.1 years, p = 0.04), younger age at diagnosis of diabetes mellitus (46.2 +/- 13.0 years, p = 0.01), having secondary education (p = 0.02), and having a history of depression (p = 0.002). Multivariate analysis showed that current age (p = 0.04), duration of diabetes mellitus (p = 0.04), age at diagnosis of diabetes mellitus (p = 0.01), and secondary education (p = 0.01) were significant factors. CONCLUSIONS: The prevalence of major depressive disorder was high among patients with type 2 diabetes mellitus. Screening of patients with type 2 diabetes mellitus for depression should be performed periodically or routinely, especially in the primary care setting. PMID- 27377490 TI - Diabetes - An ancient disease, epidemic & an economic burden for the present era. PMID- 27377491 TI - Role of anticoagulation in neurological practice. PMID- 27377492 TI - Metabolic syndrome, serious mental illnesses & lifestyle. PMID- 27377493 TI - Deleting the 'neglect' from two neglected tropical diseases in India. PMID- 27377494 TI - Intervening at prediabetes stage is critical to controlling the diabetes epidemic among Asian Indians. PMID- 27377495 TI - Evolving locally appropriate models of care for indian sickle cell disease. AB - The sickle cell gene in India represents a separate occurrence of the HbS mutations from those in Africa. Sickle cell disease in India occurs against different genetic and environmental backgrounds from those seen in African patients and there is evidence of clinical differences between the populations. Knowledge of the clinical features of African disease was drawn from the Jamaican Cohort Study, based on prospective follow up of all cases of sickle cell disease detected by the screening of 100,000 consecutive newborns in Kingston, Jamaica, and supplemented by observations from the Cooperative Study of Sickle Cell Disease in the US. Defining the principal causes of early morbidity in African sickle cell disease led to successful interventions including pneumococcal prophylaxis, parental education in the early diagnosis of acute splenic sequestration, and the early detection by trans-cranial Doppler of cerebral vessel stenosis predictive of stroke but their success depended on early diagnosis, ideally at birth. Although reducing mortality among patients with African forms of SS disease, the question remains whether these interventions are appropriate or justified in Indian patients. This dilemma is approached by comparing the available data in African and Indian forms of SS disease seeking to highlight the similarities and differences and to identify the deficiencies in knowledge of Indian disease. These deficiencies could be most readily addressed by cohort studies based on newborn screening and since much of the morbidity of African disease occurs in the first five years of life, these need not be a daunting prospect for Indian health care personnel. Newborn screening programmes for sickle cell disease are already underway in India and appropriate protocols and therapeutic trials could quickly answer many of these questions. Without this knowledge, Indian physicians may continue to use possibly unnecessary and expensive models of care. PMID- 27377496 TI - Role of laparoscopy in hepatobiliary malignancies. AB - The many benefits of laparoscopy, including smaller incision, reduced length of hospital stay and more rapid return to normal function, have seen its popularity grow in recent years. With concurrent improvements in non-surgical cancer management the importance of accurate staging is becoming increasingly important. There are two main applications of laparoscopic surgery in managing hepato pancreatico-biliary (HPB) malignancy: accurate staging of disease and resection. We aim to summarize the use of laparoscopy in these contexts. The role of staging laparoscopy has become routine in certain cancers, in particular T[2] staged, locally advanced gastric cancer, hilar cholangiocarcinoma and non-Hodgkin's lymphoma. For other cancers, in particular colorectal, laparoscopy has now become the gold standard management for resection such that there is no role for stand alone staging laparoscopy. In HPB cancers, although staging laparoscopy may play a role, with ever improving radiology, its role remains controversial. PMID- 27377497 TI - Early menopause: A hazard to a woman's health. AB - Early menopause or premature ovarian insufficiency (POI) is a common cause of infertility in women and affects about one per cent of young women. This disorder has significant psychological sequelae and major health implications. Its relevance has increased in recent years due to the fact that age of motherhood is being delayed in developed countries, with the risk of having either primary ovarian insufficiency or less possibilities of pregnancy. The main characteristics are absence of ovulation, amenorrhoea and high levels of serum gonadotropins (hypergonadotropic hypogonadism). Although the aetiology remains uncertain in most cases, several rare specific causes have been elucidated. Potential causes for POI are iatrogenic (ovarian surgery, radiotherapy or chemotherapy), environmental factors, viral infections, metabolic and autoimmune diseases, and genetic alterations. Because of the association with other autoimmune diseases, close follow up is recommended in patients with POI. The traditional indicators to evaluate ovarian ageing are age, serum hormonal levels, anti-Mullerian hormone, antral follicle count, and ultrasonography of ovaries. Hormone replacement therapy remains the mainstay of treatment, and the best chance of achieving a pregnancy is through oocyte donation. This article aims to present an overview of potential causes, clinical manifestations, and treatment options of POI. PMID- 27377498 TI - Quality of anticoagulation therapy in neurological patients in a tertiary care hospital in north India. AB - BACKGROUND & OBJECTIVES: There is paucity of studies on the quality of anticoagulation in neurological patients from India. This study evaluates the quality of oral anticoagulation therapy in neurology patients. METHODS: Consecutive patients attending a tertiary care neurology service in north India who were prescribed oral anticoagulant (OAC), were included. Their international normalized ratio (INR) values were prospectively monitored and the earlier INR values of the patients who were already on OAC were retrospectively analyzed. The patients with multi-organ dysfunction, pregnancy and those below 18 yr of age were excluded. The therapeutic INR range was defined as per standard recommendations. The level of anticoagulation, factors interfering with OAC and complications were noted. RESULTS: The results were based on 77 patients with median age 40 yr. Fifty one patients received OAC for secondary stroke prevention, 23 for cerebral venous sinus thrombosis (CVST) and three for deep vein thrombosis (DVT). A total 167.9 person-years of follow up was done with a median of 1.2 (0.3-9.3) years. of the 1287 INR reports, 505 (39.3%) reports were in the therapeutic range, 496 (38.5%) were below and 282 (21.91%) were above the therapeutic level. Stable INR was obtained in 33 (42.86%) patients only. INR level was improved by dose adjustment in 20 (26%), drug modification in two (2.6%), and dietary adjustment in six (7.8%) patients. Three patients were sensitive and five were resistant to OAC. Complications were noted in 28 instances; thromboembolic in 16 and haemorrhagic stroke in 12. The overall complication rate was 16.7 per 100 person-years. INTERPRETATION & CONCLUSIONS: It may be concluded that stable therapeutic INR is difficult to maintain in neurological patients. Optimal modification of diet, drug and dose of oral anticoagulant may help in stabilization of INR. PMID- 27377499 TI - Lifestyle related factors & impact of metabolic syndrome on quality of life, level of functioning & self-esteem in patients with bipolar disorder & schizophrenia. AB - BACKGROUND & OBJECTIVES: Though studies have reported high prevalence rates of metabolic syndrome among patients with bipolar disorder (BPAD) and schizophrenia, there is lack of data on the impact of the same on the patients' life. This study was aimed to assess the lifestyle related factors associated with metabolic syndrome (MetS) and to study the impact of MetS on functioning and quality of life (QOL) in patients with BPAD and schizophrenia. METHODS: A total of 102 patients with BPAD and 72 patients with schizophrenia attending the output unit of a tertiary care hospital in north India were evaluated for MetS. These patients were assessed on Health Promoting Lifestyle Profile scale II (HPLP II), World Health Organization QOL -Bref Version (WHOQOL-Bref), Impact of Weight on Quality of Life- Lite version (IWOQOL -Lite), Body weight, Image and Self-esteem Evaluation questionnaire (BWISE), Obesity-related Problem scale (OP scale) and Global Assessment of Functioning (GAF) scale. RESULTS: MetS was associated with lower scores on domains of health responsibility and nutrition habit domain on HPLP-II scale in both groups, and additionally on physical activity and stress management domain in BPAD group. On WHOQOL-Bref, MetS was associated with lower scores on the domains of physical and psychological health in both groups. On IWQOL-Lite, scores on personal distress and self esteem domains were higher in those with obesity in both groups and also on physical activity domain in schizophrenia group. Those with MetS had lower level of functioning as measured by GAF in schizophrenia group. Fulfillment of higher number of criteria of MetS correlated with poorer quality of life and higher problems in both groups. INTERPRETATION & CONCLUSIONS: Many modifiable lifestyle factors increase the risk of MetS. MetS was found to be associated with poorer QOL in patients with BPAD and schizophrenia; in addition, obesity led to poor self-esteem and excessive personal distress. PMID- 27377501 TI - Association of BCL11A genetic variant (rs11886868) with severity in beta thalassaemia major & sickle cell anaemia. AB - BACKGROUND & OBJECTIVES: The amount of foetal haemoglobin that persists in adulthood affects the clinical severity of haemoglobinopathies including beta thalassaemia major and sickle cell anaemia (SCA). The present study was undertaken to analyse beta-thalassaemia as well as SCA patients for the single nucleotide polymorphism (SNP), rs11886868 (T/C) in BCL11A gene and to evaluate the association between this polymorphism and severity of beta-thalassaemia major and SCA. METHODS: a total of 620 samples (420 beta-thalassaemia major and 200 SCA cases) were analysed before blood transfusion using basic screening tests like complete blood analysis and osmotic fragility and further confirmed by high performance liquid chromatography (HPLC), amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and reverse dot blot techniques. All patients were transfusion dependent. Patients with beta-thalassaemia and SCA were classified into mild, moderate, severe according to the severity score based on Hb levels, age of onset, age at which patients received their first blood transfusion, the degree of growth retardation and splenectomy. beta-thalassaemia as well as SCA patients were analysed for the SNP, rs11886868 (T/C) in BCL11A gene and association between this polymorphism and severity of beta-thalassaemia major as well as SCA was evaluated. RESULTS: There was a significant difference in genotypic and allelic frequencies of BCL11A gene polymorphism between mild and moderate and mild and severe cases in both the groups. A significant (P<0.001) difference was observed in the mean HbF levels between the three genotypes in different severity groups. HbF levels were found to be high in CC genotype bearing individuals followed by TC and TT in beta-thalassaemia major as well as SCA. INTERPRETATION & CONCLUSIONS: This study confirms that the T/C variant (rs11886868) of the BCL11A gene causing downregulation of BCL11A gene expression in adult erythroid precursors results in the induction of HbF and ameliorates the severity of beta-thalassaemia as well as SCA. PMID- 27377500 TI - Evaluation of carotid artery dynamics & correlation with cardiac & hepatic iron in beta-thalassaemia patients. AB - BACKGROUND & OBJECTIVES: Early atherosclerosis and vascular complication have been described in thalassaemia patients. There is lack of data or guidelines regarding monitoring of vascular health in thalassaemia. This study was conducted to compare carotid artery structural and functional indices such as carotid artery intima-media thickness (CIMT), stiffness index (SI) and Young's elastic modulus (YEM) in beta-thalassemia patients with age and sex matched controls, and to correlate these parameters with serum ferritin, cardiac iron, and hepatic iron. METHODS: This cross-sectional study included 53 beta-thalassaemia patients receiving regular blood transfusions. Carotid artery indices such as CIMT, SI, and YEM were calculated by duplex ultrasound and colour Doppler. Serum ferritin levels were measured by chemiluminescence. Cardiac and hepatic iron estimation were done using MRI T2* sequences analyzed by a special thalassaemia software. RESULTS: Mean CIMT of cases and controls were 0.48 +/- 0.04 and 0.44+/-0.02 mm, respectively and these were significantly different (P<0.001). Similarly significant differences were noted in SI and YEM of cases (2.45+/-0.79 and 96.12+/-34.85, respectively) as compared to controls (1.98+/-0.54 and 68.60+/ 24.29, respectively) (p<0.001). There was significant inverse correlation between stiffness index and cardiac iron overload assessed by MRI cardiac T2* (p=0.03). Mean SI and YEM of cases were (2.1736 +/- 0.2986 and 107.3+/- 41.6, respectively) significantly higher among non-splenectomized patients compared to splenectomized patients (2.0136 +/- 0.263 and 86.9 +/- 25.2, respectively) (p<0.05). INTERPRETATION & CONCLUSIONS: CIMT and arterial stiffness indices were significantly increased in beta-thalassaemia patients compared to controls which was indicative of early atherogenic changes. This study supports the hypothesis that iron overload is a risk factor for early atherosclerosis and cardiovascular disease. PMID- 27377502 TI - Association of CDKAL1, CDKN2A/B & HHEX gene polymorphisms with type 2 diabetes mellitus in the population of Hyderabad, India. AB - BACKGROUND & OBJECTIVES: The genome-wide association studies (GWAS) have shown an association of type 2 diabetes mellitus (T2DM) with several novel genes. We report here the findings on the pattern of genetic association of three genes (CDKAL1, CDKN2A/B and HHEX) with T2DM in the population of Hyderabad, south India. METHODS: A sample of 1379 individuals (758 T2DM cases and 621 controls) from Hyderabad, India, were genotyped for five single nucleotide polymorphisms (SNPs) of CDKAL1 (rs7754840, rs7756992) CDKN2A/B (rs10811661) and HHEX (rs1111875, rs7923837) genes on Sequenom Mass Array platform. RESULTS: The risk allele frequencies of the CDKAL1 and CDKN2A/B SNPs were relatively higher in cases than in the controls and the logistic regression analysis yielded significant odds ratios suggesting that the variant alleles conferred risk for developing T2DM in this population. the HHEX gene did not show either allelic or genotypic association with T2DM. The multivariate logistic regression analysis with reference to both alleles and genotypes of CDKAL1 SNPs showed significant association, suggesting an important role for this gene in the T2DM pathophysiology. INTERPRETATION & CONCLUSIONS: A significant association was seen of all the three SNPs of CDKAL1 and CDKN2A/B genes with T2DM but none of the two SNPs of HHEX. Further studies are required to cross-validate our findings in a relatively larger sample. It is also necessary to explore other SNPs of HHEX gene to unequivocally establish the pattern of association of this gene with T2DM in this population. PMID- 27377503 TI - Linking HIV & family planning services to improve dual methods of contraception among women infected with HIV in Mumbai, Maharashtra, India. AB - BACKGROUND & OBJECTIVES: Preventing unintended pregnancies among people living with HIV (PLHIV) is one of the strategies of WHO for preventing parent-to-child transmission (PPTCT). Given the limitation of only condom use, the objective of this study was to improve use of dual contraceptive methods among HIV infected women. METHODS: An experimental study among HIV positive women was conducted at two tertiary care level hospitals in Mumbai. Linking HIV with family planning services was the focus of intervention at one site and standard level of care was maintained at the control site. At each site, 150 HIV+ve women attending counselling and testing centres, who did not intend to get pregnant in the next one year and were eligible to use dual methods, were enrolled and followed up to one year. RESULTS: At the end of one year, 60 per cent women in the intervention group reached Family Planning centres compared to eight per cent in the control group. There was three times more acceptance and continuation of use of dual methods along with increase in consistent use of condoms and less number of unplanned pregnancies in the intervention group than the control group. INTERPRETATION & CONCLUSIONS: The study findings demonstrate that linking HIV and family planning services may facilitate the uptake of dual methods of contraception without reducing consistent condom use among HIV infected women. The PPTCT programmes need to focus on the component of Prong 2 of PPTCT which aims to prevent unintended pregnancies among HIV positive women. PMID- 27377504 TI - Pattern of episiotomy use & its immediate complications among vaginal deliveries in 18 tertiary care hospitals in India. AB - BACKGROUND & OBJECTIVES: In developed countries, efforts have been made to restrict episiotomy practice. However, in developing countries the episiotomy rates continue to be high. This study was conducted to evaluate the pattern of episiotomy use and its immediate complications among women delivering at tertiary level public hospitals in India. METHODS: Prospective data of all women undergoing vaginal delivery including instrumental delivery were collected daily from the labour room registers of the 18 tertiary care hospitals on a structured proforma. Weekly data from all sites were sent to a central unit for compilation and analysis. Odds ratio was used to compare the proportion of genital trauma among women with and without episiotomy both in nulliparous and multiparous women. RESULTS: Among 1,20,243 vaginal deliveries, episiotomy was performed in 63.4 per cent (n=76,305) cases. Nulliparaous women were 8.8 times more likely to undergo episiotomy than multiparous women. The various genital tract injuries reported were first degree perineal tear (n=4805, 3.9%), second degree perineal tear (n=1082, 0.9%), third and fourth degree perineal tear (n=186, 0.2%), anterior vaginal trauma requiring suturing (n=490, 0.4%), extension of episiotomy/vaginal laceration/excessive bleeding from episiotomy or tear (n=177, 0.15%), vulval/vaginal haematoma (n=70, 0.06%) and cervical tear (n=108, 0.08%). The combined rate of third and fourth degree perineal tears was observed to be significantly lower (p<0.001) among nullipara who received episiotomy (0.13%) compared to those who delivered without episiotomy (0.62%). INTERPRETATIONS & CONCLUSIONS: Significantly lower rates of third or fourth degree perineal tear were seen among nulliparous women undergoing episiotomy. The risk and benefit of episiotomy and its complications need to be evaluated through randomized clinical trials in the Indian context. PMID- 27377505 TI - Genetic diversity of Mycobacterium tuberculosis isolates from central India. AB - BACKGROUND & OBJECTIVES: There is a paucity of data available on genetic biodiversity of Mycobacterium tuberculosis isolates from central India. The present study was carried out on isolates of M. tuberculosis cultured from diagnostic clinical samples of patients from Bhopal, central India, using spoligotyping as a method of molecular typing. METHODS: DNA was extracted from 340 isolates of M. tuberculosis from culture, confirmed as M. tuberculosis by molecular and biochemical methods and subjected to spoligotyping. The results were compared with the international SITVIT2 database. RESULTS: Sixty five different spoligo international type (SIT) patterns were observed. A total of 239 (70.3%) isolates could be clustered into 25 SITs. The Central Asian (CAS) and East African Indian (EAI) families were found to be the two major circulating families in this region. SIT26/CAS1_DEL was identified as the most predominant type, followed by SIT11/EAI3_IND and SIT288/CAS[2]. Forty (11.8%) unique (non clustered) and 61 (17.9%) orphan isolates were identified in the study. There was no significant association of clustering with clinical and demographic characteristics of patients. INTERPRETATION & CONCLUSIONS: Well established SITs were found to be predominant in our study. SIT26/CAS1_DEL was the most predominant type. However, the occurrence of a substantial number of orphan isolates may indicate the presence of active spatial and temporal evolutionary dynamics within the isolates of M. tuberculosis. PMID- 27377506 TI - Analysis of expression profile of mce operon genes (mce1, mce2, mce3 operon) in different Mycobacterium tuberculosis isolates at different growth phases. AB - BACKGROUND & OBJECTIVES: Mycobacterium tuberculosis (M. tuberculosis) has four homologous mammalian cell entry (mce) operons (mce1-4) that encode exported proteins and have a possible role in the virulence mechanism of this pathogen. The expression of mce operon is considered to be complex and not completely understood. Although expression of mce operon at different in vitro growth phases has been studied earlier, its expression in different M. tuberculosis isolates under different growth phases is not yet studied. The present preliminary study was conducted on a limited number of isolates to know the trend of expression pattern of mce operon genes in different M. tuberculosis isolates under different growth stages. METHODS: In this study, we monitored the transcriptional profile of selected mce operon genes (mce1A, mce1D, mce2A, mce2D, mce3A, mce3C) in different M.tuberculosis isolates (MDR1, MDR2, and sensitive isolate) at early exponential and stationary phases using real-time quantitative PCR. RESULTS: The expression ratio of all selected mce operon genes in all M. tuberculosis isolates was reduced at the initial phase and increased substantially at a later phase of growth. Higher expression of mce1 operon genes was found in all M. tuberculosis isolates as compared to other mce operon genes (mce2 and mce3 operons) at stationary growth phase. INTERPRETATION & CONCLUSIONS: the higher expression of mce operon genes at stationary phase (as compared to early exponential phase) suggested growth phase dependent expression of mce operon genes. This indicated that the mce operon genes might have a role in M. tuberculosis survival and adaptation on the onset of adverse condition like stationary phase. Identification of differentially expressed genes will add to our understanding of the bacilli involved in adaptation to different growth conditions. PMID- 27377507 TI - Species distribution & antifungal susceptibility pattern of oropharyngeal Candida isolates from human immunodeficiency virus infected individuals. AB - BACKGROUND & OBJECTIVES: The changing spectrum of Candida species in causation of oropharyngeal candidiasis and their antifungal susceptibility pattern among the HIV infected individuals has made the identification to species level mandatory and detection of drug resistance necessary for patient care. The present study was carried out to determine the species distribution and antifungal susceptibility profile of oral Candida isolates colonizing or infecting both HIV seropositive and seronegative individuals. METHODS: A case-control study was conducted including 141 consecutive, non-repeat HIV-seropositive individuals and an equal number of sex and age matched HIV-seronegative control. Speciation of the oropharyngeal Candida isolates was done using standard yeast identification protocol. Antifungal susceptibility testing was done by the disk-diffusion method as well as by Fungitest method. RESULTS: From the 59 culture positive HIV seropositive cases, 61 Candida isolates were recovered; Candidaalbicans (n=47, 77.0%), C. dubliniensis (n=9, 14.7%), C. parapsilosis (n=2, 3.2%), C. glabrata (n=2, 3.2%), and C. famata (n=1, 1.6%). Candida colonization in HIV-seropositive individuals was significantly higher than that of HIV-seronegative (control) group. Antifungal susceptibility testing revealed (n=6, 9.3%) C. albicans isolates resistant to voriconazole and fluconazole by disk-diffusion method whereas no resistance was seen by Fungitest method. INTERPRETATION & CONCLUSIONS: C. albicans was the commonest Candida species infecting or colonizing HIV seropositive individuals. Oropharyngeal Candida isolates had high level susceptibility to all the major antifungals commonly in use. Increased level of immunosuppression in HIV-seropositives and drug resistance of non-albicans Candida species makes identification and susceptibility testing of Candida species necessary in different geographical areas of the country. PMID- 27377508 TI - Healthcare associated infections in Paediatric Intensive Care Unit of a tertiary care hospital in India: Hospital stay & extra costs. AB - BACKGROUND & OBJECTIVES: Healthcare associated infections (HAIs) increase the length of stay in the hospital and consequently costs as reported from studies done in developed countries. The current study was undertaken to evaluate the impact of HAIs on length of stay and costs of health care in children admitted to Paediatric Intensive Care Unit (PICU) of a tertiary care hospital in north India. METHODS: This prospective study was done in the seven bedded PICU of a large multi-specialty tertiary care hospital in New Delhi, India. A total of 20 children with HAI (cases) and 35 children without HAI (controls), admitted to the PICU during the study period (January 2012 to June 2012), were matched for gender, age, and average severity of illness score. Each patient's length of stay was obtained prospectively. Costs of healthcare were estimated according to traditional and time driven activity based costing methods approach. RESULTS: The median extra length of PICU stay for children with HAI (cases), compared with children with no HAI (controls), was seven days (IQR 3-16). The mean total costs of patients with and without HAI were ' 2,04,787 (US$ 3,413) and ' 56,587 (US$ 943), respectively and the mean difference in the total cost between cases and controls was ' 1,48,200 (95% CI 55,716 to 2,40,685, p<0.01). INTERPRETATION & CONCLUSIONS: This study highlights the effect of HAI on costs for PICU patients, especially costs due to prolongation of hospital stay, and suggests the need to develop effective strategies for prevention of HAI to reduce costs of health care. PMID- 27377509 TI - Prescription pattern of antidepressants in five tertiary care psychiatric centres of India. AB - BACKGROUND & OBJECTIVES: Limited data are available on prescription patterns of the antidepressants from India. We studied antidepressants' prescription pattern from five geographically distant tertiary psychiatric care centers of the India. METHOD: In this cross-sectional study, all patients who attended outpatients department or were admitted in the psychiatry wards at Lucknow, Chandigarh, Tiruvalla, Mumbai and Guwahati on a fixed day, who were using or had been prescribed antidepressant medications, were included. The data were collected on a unified research protocol. RESULTS: A total of 312 patients were included. Mean age was 39+/-14.28 yr and 149 (47.76%) were females, 277 (87.5%) were outpatients. Among the patients receiving antidepressants, 150 (48.1%) were of diagnoses other than depression. Diabetes mellitus 18 (5.78%) was the most common co-morbid medical illness. A total of 194 (62.2%) patients were using selective serotonin reuptake inhibitors (SSRIs) with escitalopram 114 (36.53%) being the most common antidepressant used. Overall, 272 (87.18%) patients were using newer antidepressants. Thirty (9.62%) were prescribed more than one antidepressant; 159 (50.96%) patients were prescribed hypnotic or sedative medications with clonazepam being the most common (n=116; 37.18%). INTERPRETATION & CONCLUSIONS: About half of the patients with diagnoses other than depression were prescribed antidepressants. SSRIs were the most common group and escitalopram was the most common medication used. Concomitant use of two antidepressants was infrequent. Hypnotic and sedatives were frequently prescribed along with antidepressants. PMID- 27377510 TI - Fatal infection in adults by pneumolysin & autolysin producing, non-vaccine serotype Streptococcus pneumonia. PMID- 27377511 TI - Declining HIV seropositivity: Ten years experience from a tertiary care hospital in central India. PMID- 27377513 TI - Adherence to research reporting guidelines is needed. PMID- 27377512 TI - Serogroup distribution, antibiogram patterns & prevalence of ESBL production in Escherichia coli. PMID- 27377514 TI - Authors' response. PMID- 27377515 TI - Superior mesenteric artery (Wilkie's) syndrome following expeditious weight loss. PMID- 27377516 TI - Warfarin induced skin necrosis. PMID- 27377517 TI - Mean platelet volume as a predictive marker for venous thromboembolism and mortality in patients treated for diffuse large B-cell lymphoma. AB - It has been suggested that mean platelet volume (MPV) is associated with the risk of venous thromboembolism (VTE) and increased mortality in patients with cancer. We evaluated the association of MPV with VTE and mortality in patients treated for diffuse large B-cell lymphoma (DLBCL). Retrospective analyses were performed on 184 adult patients (median age 59, 55% men), of whom 141 were newly diagnosed, and 43 had relapse/refractory DLBCL. During the observation period (median 499 days), 39 (21.2%) patients developed VTE. Thirty-nine patients died of various causes. In univariate analysis, only the MPV and the treatment line were associated with the occurrence of VTE. In multivariate analysis, MPV <=10th percentile (odd ratio 1.81; 95% confidence interval 1.06-3.11, p = 0.03) and salvage therapy (odd ratio 2.46; 95% confidence interval 1.66-3.65, p < 0.001) remained significant factors for developing VTE. Other patient-related factors age, gender, disease-related factors-stage, the International Prognostic Index score, DLBCL subclassification (the germinal centre type and the activated B-cell type), Ki-67 index and VTE risk assessment model failed to be prognostic for VTE. In a Kaplan-Meier analysis, patients with MPV >10th percentile had statistically significantly longer VTE-free survival than patients with lower MPV. In multivariable Cox regression analysis, MPV <=10th percentile (hazard ratio 5.56, p < 0.001), male gender, age, Ki-67 index, high or high-intermediate International Prognostic Index and VTE development (hazard ratio 7.81, p = 0.029) all significantly correlated with the risk of mortality. The probability of survival was higher in patients with MPV >10th percentile. In conclusion, our results suggest that the pre-chemotherapy MPV value is a cheap and available parameter that may be a useful prognostic marker for a significant risk of VTE and inferior survival rates in patients with DLBCL. PMID- 27377518 TI - Preventing Endoscopy Clinic No-Shows: Prospective Validation of a Predictive Overbooking Model. AB - OBJECTIVES: Patient absenteeism for scheduled visits and procedures ("no-show") occurs frequently in healthcare systems worldwide, resulting in treatment delays and financial loss. To address this problem, we validated a predictive overbooking system that identifies patients at high risk for missing scheduled gastrointestinal endoscopy procedures ("no-shows" and cancellations), and offers their appointments to other patients on short notice. METHODS: We prospectively tested a predictive overbooking system at a Veterans Administration outpatient endoscopy clinic over a 34-week period, alternating between traditional booking and predictive overbooking methods. For the latter, we assigned a no-show risk score to each scheduled patient, utilizing a previously developed logistic regression model built with electronic health record data. To compare booking methods, we measured service utilization-defined as the percentage of daily total clinic capacity occupied by patients-and length of clinic workday. RESULTS: Compared to typical booking, predictive overbooking resulted in nearly all appointment slots being filled-2.5 slots available during control weeks vs. 0.35 slots during intervention weeks, t(161)=4.10, P=0.0001. Service utilization increased from 86% during control weeks to 100% during intervention weeks, allowing 111 additional patients to undergo procedures. Physician and staff overages were more common during intervention weeks, but less than anticipated (workday length of 7.84 h (control) vs. 8.31 h (intervention), t(161)=2.28, P=0.02). CONCLUSIONS: Predictive overbooking may be used to maximize endoscopy scheduling. Future research should focus on adapting the model for use in primary care and specialty clinics. PMID- 27377519 TI - Randomized Trial of Endoscopist-Controlled vs. Assistant-Controlled Wire-Guided Cannulation of the Bile Duct. AB - OBJECTIVES: Biliary cannulation is frequently the most difficult component of endoscopic retrograde cholangiopancreatography (ERCP). Techniques employed to improve safety and efficacy include wire-guided access and the use of sphincterotomes. However, a variety of options for these techniques are available and optimum strategies are not defined. We assessed whether the use of endoscopist- vs. assistant-controlled wire guidance and small vs. standard diameter sphincterotomes improves safety and/or efficacy of bile duct cannulation. METHODS: Patients were randomized using a 2 * 2 factorial design to initial cannulation attempt with endoscopist- vs. assistant-controlled wire systems (1:1 ratio) and small (3.9Fr tip) vs. standard (4.4Fr tip) sphincterotomes (1:1 ratio). The primary efficacy outcome was successful deep bile duct cannulation within 8 attempts. Sample size of 498 was planned to demonstrate a significant increase in cannulation of 10%. Interim analysis was planned after 200 patients-with a stopping rule pre-defined for a significant difference in the composite safety end point (pancreatitis, cholangitis, bleeding, and perforation). RESULTS: The study was stopped after the interim analysis, with 216 patients randomized, due to a significant difference in the safety end point with endoscopist- vs. assistant-controlled wire guidance (3/109 (2.8%) vs. 12/107 (11.2%), P=0.016), primarily due to a lower rate of post-ERCP pancreatitis (3/109 (2.8%) vs. 10/107 (9.3%), P=0.049). The difference in successful biliary cannulation for endoscopist- vs. assistant-controlled wire guidance was -0.5% (95% CI-12.0 to 11.1%) and for small vs. standard sphincerotome -0.9% (95% CI-12.5 to 10.6%). CONCLUSIONS: Use of the endoscopist- rather than assistant-controlled wire guidance for bile duct cannulation reduces complications of ERCP such as pancreatitis. PMID- 27377520 TI - Long-Term Clinical Outcomes of Rectal Neuroendocrine Tumors According to the Pathologic Status After Initial Endoscopic Resection: A KASID Multicenter Study. AB - OBJECTIVES: With advances in diagnostic endoscopy, the detection of rectal neuroendocrine tumors (NETs) has increased. However, clinical outcomes, especially after endoscopic treatment, are still unclear. The aim of this study was to determine the long-term clinical outcomes of endoscopically resected rectal NETs according to the pathologic status after initial resection. METHODS: In this large, multicenter, retrospective cohort study, we analyzed the medical records of patients who underwent endoscopic resection of rectal NETs and were followed for >=24 months at 16 university hospitals. The outcomes of interest were local or distant recurrence and metachronous lesions. RESULTS: On the pathologic assessment of 407 patients, the resection margin status was positive in 76 (18.7%) and indeterminate in 72 (17.7%) patients. Patients whose rectal NETs were diagnosed or suspected as NETs before resection showed a much higher complete resection rate than those whose tumors were resected as polyps and then diagnosed (P<0.001). Fourteen patients received salvage treatment at 1.9+/-2.8 months after initial treatment. During a median follow-up period of 45.0 months, local recurrence occurred in 3 (0.74%) patients, but there was no recurrence in the lymph nodes or distant organs. Metachronous rectal NETs were diagnosed in 3 (0.74%) patients. According to the pathologic status after initial resection, local recurrence and metachronous lesions occurred in 1 (0.4%) and 2 (0.8%) patients, respectively, in the pathologic tumor-free group, whereas they occurred in 2 (1.4%) and 1 (0.7%) patients, respectively, in the indeterminate group. CONCLUSIONS: Considering the long-term prognosis including that for recurrences or metachronous lesions, endoscopic resection is an efficient and a safe modality for the treatment of rectal NETs. This treatment may result in favorable clinical outcomes in patients with tumors of indeterminate pathology, as well as in pathologic tumor-free cases after initial resection. PMID- 27377522 TI - Pushing the Limit: How to Get the Most Out of Cold Snares. PMID- 27377521 TI - Impact of Single- vs. Split-Dose Low-Volume Bowel Preparations on Bowel Movement Kinetics, Patient Inconvenience, and Polyp Detection: A Prospective Trial. AB - OBJECTIVES: There are little data on bowel movement (BM) kinetics induced by bowel preparation. Whether single-dose (SID) or split-dose (SPD) regimens differ in terms of patient convenience is unclear. We compared BM kinetics, sleep and travel disruptions, and polyp detection rates in patients undergoing colonoscopy assigned to SID vs. SPDs. METHODS: Patients were randomly assigned to 2-L SID or SPD (SPD1 and SPD2) bowel preparations. Surveys were completed querying the onset, duration, cessation, and intensity of BMs, along with sleep and travel disruption en route to the endoscopy center. Colon cleansing quality and polyp histology were recorded. RESULTS: A total of 341 patients were enrolled, 51% in SPD and 49% in SID. Over half of patients had their first BM within 60 min of starting the preparation. After dosing, 92% of SID and 66% of SPD1 patients achieved clear effluent (P<0.001), whereas it was reported in 97% of SPD2 patients (P=0.028 vs. SID). Total duration (P=0.041) and intensity (P<0.001) of BMs were greater in SID. More patients in SID woke up for BMs (65.9 vs. 48.8%, P<0.003). No differences in the need to stop driving en route to colonoscopy were noted. Bowel prep quality was better in SPD (P<0.001). Although no difference in the adenoma detection rate was noted, the sessile-serrated polyp detection rate was greater in SPD than in SID (9.9 vs. 2.4%, P=0.004). CONCLUSIONS: Our data demonstrate that SPD bowel preparation results in decreased intensity and duration of BMs, less patient inconvenience, improved bowel preparation, and increased sessile-serrated polyp detection rates. PMID- 27377523 TI - The Development of Irritable Bowel Syndrome: A Prospective Community-Based Cohort Study. AB - OBJECTIVES: It remains controversial whether psychosocial burden is an independent predictor of irritable bowel syndrome (IBS) or occurs concurrently as an epiphenomenon. Here we prospectively examine the individual contribution of psychosocial risk factors, demographic factors, somatic symptoms, and gastrointestinal infection within a non-clinical, IBS-free population before infection occurred. METHODS: A prospective community-based cohort study including a consecutive sample of healthy participants with an elevated risk of developing gastrointestinal infection during long-distance travel was conducted. Potential predictive factors were investigated using validated self-report scales pre travel, 1 week after return, and 7 months post-travel. IBS was assessed using the ROME-III Diagnostic Questionnaire. RESULTS: Of the 1,964 eligible long-distance travelers, 1,464 responded at follow-up directly after their journey, and 1,190 participants completed the study 7 months post-journey. Fifty-three percent of study completers were female, mean age was 39.9 (s.d.=15.7) years. The mean travel duration was 40.8 (s.d.=52.8) days, and 43.3% (95% confidence interval (CI)=40.4-46.1%) of participants experienced at least moderate infectious travelers' diarrhea. The incidence of newly developed IBS 7 months post-travel was 7.2% (95%CI=5.8-8.6%). In multivariate analyses, female gender, vulnerability to diarrhea under stress, baseline somatic symptom burden, baseline illness anxiety, diarrhea within the 4 months pre-travel, and travelers' diarrhea during the journey significantly predicted IBS post-travel. CONCLUSION: This study indicates that gastrointestinal infection as well as predisposing factors such as female gender, vulnerability to diarrhea under stress, illness anxiety, and somatic symptom burden predict the development of IBS. The results indicate the necessity of simultaneously addressing both somatic and psychological needs in patients with IBS as early as possible. PMID- 27377524 TI - Outcomes of Patients with Pulmonary Atresia and Major Aortopulmonary Collaterals Without Intervention in Infancy. AB - Treatment of pulmonary atresia with major aortopulmonary collaterals (PA MAPCAs) remains a challenge. Despite variations in surgical technique, contemporary strategies all include initial intervention in the first year of life. However, a subset of patients presents later in life, and contemporary outcomes of this group have not been reported previously. We performed a retrospective case series of consecutive cases of PA MAPCAs who were seen at our center between January 2001 and February 2016, who had not undergone surgery before the age of 1 year. We describe their presenting characteristics, operative and transcatheter interventions, and outcomes. A total of eight cases were identified from 76 children with PA MAPCAs treated over the study period. Median age at presentation was 5.9 years. Seventy-five percent had confluent pulmonary arteries with a median Nakata index of 113 mm(2)/m(2). Operative intervention was performed in 5/6 cases. Two are awaiting intervention. The combination of operative and transcatheter interventions allowed for ventricular septal defect closure in 60 % of cases, all of whom had subsystemic right ventricular pressures. Operative intervention is possible in some older cases with PA and MAPCAs. Though multiple operations and transcatheter therapies are necessary, some can achieve operative correction of serial circulation with tolerable physiology. Subjects with ventricular hypoplasia and those without confluent pulmonary arteries are more challenging. PMID- 27377525 TI - Oral Enoximone as an Alternative to Protracted Intravenous Medication in Severe Pediatric Myocardial Failure. AB - Phosphodiesterase 3 inhibitors have been used successfully in pediatric patients with acute or chronic myocardial dysfunction over the last two decades. Their protracted continuous intravenous administration is associated with risk of infectious and thromboembolic complications. Weaning intravenous medication and starting oral angiotensin-converting enzyme (ACE) inhibitors and/or beta-blockers can be challenging. We reviewed retrospectively hospital records of 48 patients receiving oral enoximone treatment in a single tertiary pediatric cardiac center between November 2005 and April 2014. Failure to wean from intravenous milrinone infusion and/or intolerance of ACE inhibitors and/or beta-blockers was indications for oral enoximone treatment. Age of the patients ranged between 0.5 and 191 months (median 7.5 months) at the time of starting enoximone treatment. There were 14 patients (29 %) with left ventricular dysfunction due to myocarditis or dilated cardiomyopathy and 34 patients (71 %) with myocardial dysfunction complicating congenital heart disease. Fifteen (44 %) of these 34 patients had left ventricular dysfunction, 13 (38 %) right ventricular dysfunction, and in 6 (18 %) both ventricles were failing. Duration of oral enoximone treatment was between 3 days and 34 months (median of 2.3 months). Myocardial functional recovery allowed for weaning of enoximone treatment in 15 patients (31 %) after 6 days-15 months (median 5 months). No adverse hemodynamic effects were noted. Blood stained gastric aspirates encountered in two patients resolved with concomitant milk administration. Based on our limited experience, oral enoximone is a well-tolerated and promising alternative to intravenous medication and/or other commonly used oral medications in selected pediatric patients with chronic heart failure. PMID- 27377527 TI - Bone-Specific Alkaline Phosphatase in Patients Who Have Undergone the Fontan Operation. AB - Bone-specific alkaline phosphatase (BALP) is produced by osteoblasts. A recent series noted a positive association between cardiac index (CI) and BALP in patients with Fontan circulation. CI is low at baseline in these patients, and small decreases in CI may result in diverting of blood away from bone. We prospectively enrolled 15 patients (males <= 14 yo, females <= 12 yo) who had previously undergone Fontan operation and were undergoing cardiac catheterization. Serum BALP was measured at catheterization, and analysis performed to evaluate association between age-/gender-specific BALP z-score and CI as well as other patient variables. The median age at catheterization was 5.6 years (3.1-13.1), and time from Fontan was 1.5 years (0.1-12.1). The median superior vena cava saturation (SVC) was 65 % (52-74), median average between SVC and inferior vena cava (IVC) saturations was 62.5 % (51-70), and median CI was 3.8 L/min/m(2) (2.0-8.4). The median BALP was 65 IU/L and BALP z-score was -2.1 ( 3.2 to 0.9). BALP z-score was not associated with CI (rho = -0.1, p = 0.7), but a positive correlation was noted with the average of SVC and IVC saturation (rho = 0.5, p = 0.052) and with SVC saturation (rho = 0.4, p = 0.07), both nearly reaching statistical significance. In our cohort of children with Fontan circulation undergoing catheterization, BALP z-score was not associated with CI, but an association with estimates of mixed venous saturation was noted that nearly reached statistical significance. We hypothesize that BALP is a marker of oxygen delivery in those with Fontan circulation and may represent a valuable biomarker in this population. PMID- 27377526 TI - Noninvasive Assessment of Pulmonary Artery Pressure in Patients with Extracardiac Conduit Total Cavopulmonary Connection. AB - To assess quantitative measurement of mean pulmonary artery pressure (PAP) in extracardiac total cavopulmonary connection (TCPC) patients by noninvasive echocardiographic inferior vena cava collapsibility index (IVC-CI) and also correlation between the peripheral vein pressure and mean PAP. In 19 TCPC patients with at least 1-year follow-up after completion of TCPC, complete echocardiography including IVC-CI was recorded. All patients underwent cardiac catheterization for mean PAP pressure, peripheral vein pressure (PVP) and contrast study. Different cutoff points of mean PAP were analyzed, and based on the highest cutoff point, patients were categorized into two groups: mean PAP < 17 mmHg (acceptable) and > = 17 mmHg (high) for comparison analysis. Between 2006 and 2015, from 43 patients who had undergone TCPC, nineteen patients with a mean age 12.9 +/- 6.6 years and mean follow-up time of 3.4 +/- 1.9 years were included in this study. Mean PAP was 14.6 +/- 3.97 (range 8-22 mmHg). Thirteen (68 %) patients had PAP < 17 mmHg. No significant statistical difference was detected with respect to age, sex, type of congenital heart disease and fenestration between these two groups. But, right ventricular dominancy was more prevalent in the high PAP group (50 % vs. 7.7 % P value 0.03). IVC-CI had a correlation with mean PAP (r 0.67, P < 0.001). IVC-CI < 21.8 % can predict PAP > = 17 mmHg with 83 % sensitivity and 100 % specificity. Regression analysis proposed an equation for PAP measurement: PAP (mmHg) = 20.2097-0.1796 * (IVC-CI), (r2 = 0.56). Peripheral vein pressure measurement also showed a good correlation with mean PAP and may be used to estimate PAP with the following equation: PAP (mmHg) = 0. 8675 * PVP, (r 0.90, P < 0.0001). In conclusion, IVC-CI as noninvasive and peripheral vein pressure measurement as a minimal invasive method may be useful for quantitative estimation of PAP in patients with extracardiac TCPC. PMID- 27377528 TI - Radiation Dose and Image Quality in Pediatric Cardiac Computed Tomography: A Comparison Between Sequential and Third-Generation Dual-Source High-Pitch Spiral Techniques. AB - The aim of this study was to investigate whether there is a reduction in radiation dose and improvement in image quality of pediatric cardiac computed tomography scans performed using the high-pitch spiral technique on a new third generation dual-source 2 * 192-slice scanner (group B) compared with scans performed using the sequential technique on a single-source 256-slice scanner (group A). We performed a retrospective observational study on 40 patients aged <=18 years who underwent prospectively electrocardiogram-triggered cardiac computed tomography. Image quality was assessed by pre-defined objective indices and a four-point subjective score. Apart from a higher mean heart rate in group A (P = 0.016), there were otherwise no significant inter-group differences in patient characteristics. The median effective dose was 4.41 mSv (interquartile range 2.58-5.90 mSv) in group A and 0.52 mSv (interquartile range 0.39-0.59 mSv) in group B (P < 0.001), representing a 88 % reduction. Subjective image quality score was significantly better in group B (4 = excellent with no artifact, mode 57.1 %) than in group A (3 = good with mild artifact, mode 57.9 %) (P < 0.001). Noise index, signal-to-noise ratio and contrast-to-noise ratio between both groups were not statistically significant. New third-generation dual-source high pitch spiral scan technique can deliver excellent image quality with low radiation dose. Our results suggest that it should be considered as a first choice technique for performing cardiac computed tomography in the pediatric population. PMID- 27377529 TI - Red Blood Cell Transfusion in the Postoperative Care of Pediatric Cardiac Surgery: Survey on Stated Practice. AB - The optimal red blood cell transfusion threshold for postoperative pediatric cardiac surgery patients is unknown. This study describes the stated red blood cell transfusion practice of physicians who treat postoperative pediatric cardiac surgery patients in intensive care units. A scenario-based survey was sent to physicians involved in postoperative intensive care of pediatric cardiac surgery patients in all Canadian centers that perform such surgery. Respondents reported their red blood cell transfusion practice in four postoperative scenarios: acyanotic or cyanotic cardiac lesion, in a neonate or an infant. In part A of each scenario, the patient was critically ill, but stabilized; in part B, the patient became unstable. Response rate was 58 % (71 of 123), with 45 respondents indicating direct involvement in postoperative intensive care. There was a wide variability in stated transfusion threshold, ranging from <7.0-14.0 g/dL for stabilized cases. There was no significant difference between neonates and infants in stated transfusion threshold. The mean hemoglobin level below which respondents would transfuse a stabilized patient was 9 g/dL for acyanotic and 11.2 g/dL for cyanotic patients, a statistically significant difference (2.2 +/- 0.9 g/dL, p < 0.001). All clinical determinants of instability significantly increased transfusion threshold. Hemodynamic instability increased transfusion threshold by 2.3 +/- 1.3 g/dL in acyanotic patients and by 1.3 +/- 1.1 g/dL in cyanotic patients. Cyanotic lesion and clinical instability, but not patient age, increased stated red blood cell transfusion threshold. Significant variation in reported red blood cell transfusion practice exists among physicians treating pediatric patients in intensive care following cardiac surgery. PMID- 27377530 TI - Pigmentary traits and use of indoor tanning beds in a cohort of women. PMID- 27377531 TI - The application of cholesky decomposition in valence bond calculation. AB - The Cholesky decomposition (CD) technique, used to approximate the two-electron repulsion integrals (ERIs), is applied to the valence bond self-consistent field (VBSCF) method. Test calculations on ethylene, C2 n H2 n +2 , and C2 n H4 n -2 molecules (n = 1-7) show that the performance of the VBSCF method is much improved using the CD technique, and thus, the integral transformation from basis functions to VB orbitals is no longer the bottleneck in VBSCF calculations. The errors of the CD-based ERIs and of the total energy are controlled by the CD threshold, for which a value of 10(-6) ensures to control the total energy error within 10(-6) Hartree. (c) 2016 Wiley Periodicals, Inc. PMID- 27377532 TI - Origin of Nanobubbles Electrochemically Formed in a Magnetic Field: Ionic Vacancy Production in Electrode Reaction. AB - As a process complementing conventional electrode reactions, ionic vacancy production in electrode reaction was theoretically examined; whether reaction is anodic or cathodic, based on the momentum conservation by Newton's second law of motion, electron transfer necessarily leads to the emission of original embryo vacancies, and dielectric polarization endows to them the same electric charge as trans- ferred in the reaction. Then, the emitted embryo vacancies immediately receive the thermal relaxation of solution particles to develop steady-state vacancies. After the vacancy production, nanobubbles are created by the collision of the vacancies in a vertical magnetic field. PMID- 27377533 TI - Plasma IFN-gamma and IL-6 levels correlate with peripheral T-cell numbers but not toxicity in RCC patients treated with CAR T-cells. AB - Autologous T-cells genetically modified to express a chimeric antigen receptor (CAR) against carboxy-anhydrase-IX (CAIX) were administered to twelve patients with CAIX-positive metastatic renal cell carcinoma. Here, we questioned whether plasma cytokine levels following treatment or in vitro cytokine production from the T-cell infusion products could serve as predictors for peripheral T-cell persistence or in vivo T-cell activity. We demonstrated that CAR surface as well as gene expression are down-regulated following T-cell infusion, and that peripheral numbers of CAR T-cells are best captured by flow cytometry and not by qPCR. Numbers of CAR T-cells in blood correlated with plasma levels of IFN-gamma and IL-6, but not with any of the other cytokines tested. Plasma IFN-gamma or IL 6 levels did not correlate with liver enzyme values. Thus, out of 27 cytokines tested, IFN-gamma and IL-6 levels in plasma are potential surrogate markers for CAR T-cell persistence in solid tumors. PMID- 27377535 TI - Distinct origins, gene expression and function of microglia and monocyte-derived macrophages in CNS myelin injury and regeneration. AB - Central nervous system (CNS) injury incurs a rapid innate immune response, including that from macrophages derived from endogenous microglia and circulating monocytes infiltrating the lesion site. One example of such injury is the demyelination observed in the autoimmune disease multiple sclerosis (MS), where macrophages are implicated in both myelin injury and regeneration. Although initially microglia and monocyte-derived macrophages were considered to have identical origins, gene expression, and function, recent advances have revealed important distinctions in all three categories and have caused a paradigm shift in view of their unique identity and roles. This has important consequences for understanding their individual contribution to neurological function and therapeutic targeting of these populations in diseases like MS. Here, we address the differences between CNS endogenous and exogenously-derived macrophages with a particular focus on myelin damage and regeneration. PMID- 27377534 TI - Adoptive transfer of natural killer cells promotes the anti-tumor efficacy of T cells. AB - The density of NK cells in tumors correlates positively with prognosis in many types of cancers. The average number of infiltrating NK cells is, however, quite modest (approximately 30 NK cells/sq.mm), even in tumors deemed to have a "high" density of infiltrating NK cells. It is unclear how such low numbers of tumor infiltrating NK cells can influence outcome. Here, we used ovalbumin-expressing tumor cell lines and TCR transgenic, OVA-specific cytotoxic T lymphocytes (OT-I CTLs) to determine whether the simultaneous attack by anti-tumor CTLs and IL-2 activated NK (A-NK) cells synergistically increases the overall tumor cell kill and whether upregulation of tumor MHC class-I by NK cell-derived interferon-gamma (IFNgamma) improves tumor-recognition and kill by anti-tumor CTLs. At equal E:T ratios, A-NK cells killed OVA-expressing tumor cells better than OT-I-CTLs. The cytotoxicity against OVA-expressing tumor cells increased by combining OT-I-CTLs and A-NK cells, but the increase was additive rather than synergistic. A-NK cells adenovirally-transduced to produce IL-12 (A-NKIL-12) produced high amounts of IFNgamma. The addition of a low number of A-NKIL-12 cells to OT-I-CTLs resulted in a synergistic, albeit modest, increase in overall cytotoxicity. Pre-treatment of tumor cells with NK cell-conditioned medium increased tumor MHC expression and sensitivity to CTL-mediated killing. Pre-treatment of CTLs with NK cell conditioned medium had no effect on CTL cytotoxicity. In vivo, MHC class-I expression by OVA-expressing B16 melanoma lung metastases increased significantly within 24-48h after adoptive transfer of A-NKIL-12 cells. OT-I-CTLs and A-NKIL-12 cells localized selectively and equally well into OVA-expressing B16 lung metastases and treatment of mice bearing 7-days-old OVA-B16 lung metastases with both A-NKIL-12 cells and OT-I-CTLs lead to a significant prolongation of survival. Thus, an important function of tumor-infiltrating NK cells may be to increase tumor cell expression of MHC class-I through secretion of IFNgamma, to prepare them for recognition by tumor-specific CTLs. PMID- 27377536 TI - The contribution of neutrophils to CNS autoimmunity. AB - Multiple sclerosis (MS) is believed to be initiated when myelin-specific T cells infiltrate the central nervous system (CNS), triggering subsequent recruitment of inflammatory leukocytes to the CNS. The contribution of neutrophils to CNS autoimmune disease has been underappreciated, but several studies in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, indicate that neutrophils have an important role in inflammation. Neutrophils are hypothesized to contribute to the pathogenesis of EAE by producing cytokines and promoting breakdown of the blood brain barrier. Neutrophils may also influence the manifestation of EAE by facilitating parenchymal brain inflammation. This review summarizes evidence supporting a functional role for neutrophils in EAE and MS, highlighting the differential regulation of neutrophil recruitment in the brain and spinal cord. PMID- 27377537 TI - Downscaled and debiased climate simulations for North America from 21,000 years ago to 2100AD. AB - Increasingly, ecological modellers are integrating paleodata with future projections to understand climate-driven biodiversity dynamics from the past through the current century. Climate simulations from earth system models are necessary to this effort, but must be debiased and downscaled before they can be used by ecological models. Downscaling methods and observational baselines vary among researchers, which produces confounding biases among downscaled climate simulations. We present unified datasets of debiased and downscaled climate simulations for North America from 21 ka BP to 2100AD, at 0.5 degrees spatial resolution. Temporal resolution is decadal averages of monthly data until 1950AD, average climates for 1950-2005 AD, and monthly data from 2010 to 2100AD, with decadal averages also provided. This downscaling includes two transient paleoclimatic simulations and 12 climate models for the IPCC AR5 (CMIP5) historical (1850-2005), RCP4.5, and RCP8.5 21st-century scenarios. Climate variables include primary variables and derived bioclimatic variables. These datasets provide a common set of climate simulations suitable for seamlessly modelling the effects of past and future climate change on species distributions and diversity. PMID- 27377539 TI - Occurrence of enteric viruses in reclaimed and surface irrigation water: relationship with microbiological and physicochemical indicators. AB - AIMS: To assess the prevalence of enteric viruses in different irrigation water sources and in the irrigated produce, and the possible links with microbiological and physicochemical water characteristics. METHODS AND RESULTS: The prevalence and levels of Escherichia coli, Norovirus (NoV) genogroup I (GI) and II (GII), as well as Hepatitis A virus were assessed in three types of water: surface water (surface-W), reclaimed water subjected to secondary treatment (secondary-W) and reclaimed water subjected to tertiary treatment (tertiary-W), as well as in zucchini irrigated with these irrigation water sources. Chemical oxygen demand (COD), turbidity, total suspended solids, alkalinity and maximum filterable volume (MFV) were also measured in the water. Higher prevalence of NoV in secondary-W (GI 100%, GII 55.6%) and tertiary-W (GI 91.7%, GII 66.7%) compared with surface-W (GI 58.4%, GII 22.2%) was observed. Nov GI showed positive correlation with E. coli (Spearman's correlation coefficient = 0.68, P < 0.01), and with some physicochemical parameters such as COD (0.52, P < 0.01), turbidity (0.52, P < 0.01) and MFV (0.54, P < 0.01). Escherichia coli and enteric viruses were not detected in zucchini. CONCLUSION: There is a potential risk of contamination of crops with NoV when reclaimed water is used for irrigation. SIGNIFICANCE AND IMPACT OF THE STUDY: Increase the knowledge on the prevalence of enteric viruses in different irrigation water sources, and its consequences for fresh produce safety. PMID- 27377538 TI - Assessing supply-side barriers to uptake of intermittent preventive treatment for malaria in pregnancy: a qualitative study and document and record review in two regions of Uganda. AB - BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP), provided as part of routine antenatal care (ANC), is one of three malaria-in-pregnancy prevention and control mechanisms recommended by the World Health Organization (WHO). However, despite high ANC attendance and increased efforts to address known obstacles, IPTp uptake figures have remained low. This study aimed to identify and assess barriers that continue to impede IPTp uptake in Uganda, in particular for women who attend ANC. The paper focuses on supply-side barriers, i.e., challenges relating to the health service provider. METHODS: In-depth interviews were conducted in two regions of Uganda in November 2013 and April/May 2014 with four different target audiences: seven district health officials, 15 health workers, 19 women who had attended ANC, and five opinion leaders. In addition, a document and record review was carried out at four health facilities. RESULTS: Guidelines with regard to IPTp provision in Uganda have been shown to be inconsistent and, at the time of the research, did not reflect the most recent WHO policy recommendation. There is a lack of training and supervision opportunities for health workers, resulting in poor knowledge of IPTp guidelines and uncertainty about the safety and efficacy of SP. ANC is not consistently offered in health facilities, leading to some women being denied services. While strengthening of the supply chain appears to have reduced the occurrence of stock-outs of SP in public facilities, stock-outs reportedly continue to occur in the private sector. There are also sources of data inaccuracy along the data recording and reporting chain, limiting policy makers' ability to react adequately to trends and challenges. CONCLUSIONS: Given the high ANC attendance rates in Uganda, supply-side barriers are likely to account for many missed opportunities for the provision of IPTp in Uganda. Improvements will require consistent provision of ANC, implementation of current WHO IPTp policy recommendations, supply of SP to the private sector, availability of clear guidelines, as well as improved training and supervision for health workers. Improving facility and district-level recording and reporting will further strengthen the country's ability to address uptake of IPTp. PMID- 27377540 TI - Biventricular repair of pulmonary atresia with intact ventricular septum and severely hypoplastic right ventricle: a case report of a minimum intervention surgical approach. AB - BACKGROUND: In patients who have pulmonary atresia with an intact ventricular septum and severe right ventricular hypoplasia, biventricular repair is considered to be impossible and multiple interventions are generally required for definitive repair. CASE PRESENTATION: An initial palliative procedure was performed in a 1-month-old boy to promote right ventricular development by pulmonary valvectomy without disrupting the annulus, and appropriate oxygenation was achieved with a central funnel shunt. The retained annulus caused functional stenosis and prevented unfavorable right ventricular dilatation due to regurgitation. Thirteen years later, without any other intervention, reconstruction of the right ventricular outflow tract was successfully performed for definitive biventricular repair by using a new expanded polytetrafluoroethylene bulging valved conduit with extended longevity. CONCLUSIONS: The successful outcome in this case suggests that our minimal palliation strategy could be one option for management of these patients. PMID- 27377541 TI - EU regulation of endocrine disruptors: a missed opportunity. PMID- 27377542 TI - Effects of long-term testosterone administration on cognition in older men with low or low-to-normal testosterone concentrations: a prespecified secondary analysis of data from the randomised, double-blind, placebo-controlled TEAAM trial. AB - BACKGROUND: The effects of testosterone on cognitive function in older men are incompletely understood. We aimed to establish the effects of long-term testosterone administration on multiple domains of cognitive function in older men with low or low-to-normal testosterone concentrations. METHODS: We did the randomised, double-blind, placebo-controlled, parallel-group TEAAM trial at three medical centres in Boston, Phoenix, and Los Angeles, USA. Men aged 60 years and older with low or low-to-normal testosterone concentrations (3.47-13.9 nmol/L, or free testosterone <173 pmol/L) were randomly assigned (1:1), via computer generated randomisation, to receive either 7.5 g of 1% testosterone gel or placebo gel daily for 3 years. Randomisation was stratified by age (60-75 years vs >75 years) and study site. The testosterone dose was adjusted to achieve concentrations of 17.3-31.2 nmol/L. Participants and all study personnel were masked to treatment allocation. Multiple domains of cognitive function were assessed as prespecified secondary outcomes by use of standardised tests at baseline and months 6, 18, and 36. We did analyses by intention to treat (in men who had baseline assessments of cognitive function) and per protocol (restricted to participants who completed the study drug and had both baseline and 36 month assessments of cognitive function). The TEAAM trial is registered with ClinicalTrials.gov, number NCT00287586. FINDINGS: Between Sept 1, 2004, and Feb 12, 2009, we randomly assigned 308 participants to receive either testosterone (n=156) or placebo (n=152). 280 men had baseline cognitive assessments (n=140 per group). Mean follow-up time was 29.0 months (SD 11.5) in the testosterone group and 31.1 months (9.5) in the placebo group. The last participant completed the study on May 11, 2012. In the testosterone group, mean concentrations of serum total testosterone increased from 10.6 nmol/L (SD 2.2) to 19.7 nmol/L (9.2) and free testosterone concentrations increased from 222 pmol/L (62) to 364 pmol/L (222). In the placebo group, mean concentrations of serum total testosterone were 10.7 nmol/L (SD 2.3) at baseline and 11.1 nmol/L (3.2) post-intervention and free testosterone concentrations were 210 pmol/L (61) and 172 pmol/L (49), respectively. We recorded no between-group differences in changes in visuospatial ability (mean difference: Complex Figure Test -0.51, 95% CI -2.0 to 1.0), phonemic or category verbal fluency (phonemic fluency test 0.90, -1.3 to 3.1; categorical fluency test 1.1, -0.3 to 2.6), verbal memory (paragraph recall test 0.29, -1.2 to 1.8), manual dexterity (Grooved Pegboard Test 4.2, -1.3 to 9.7), and attention or executive function (Stroop Interference Test -2.6, -7.4 to 2.3) after adjustment for age, education, and baseline cognitive function. In both the intention-to-treat and per-protocol (n=86 per group) populations, changes in cognitive function scores were not related significantly to changes in total or free testosterone, or oestradiol concentrations. INTERPRETATION: Testosterone administration for 36 months in older men with low or low-to-normal testosterone concentrations did not improve cognitive function. Future long-term trials are needed to investigate the efficacy of testosterone replacement in patients with impaired cognition, such as people with Alzheimer's disease. FUNDING: AbbVie Pharmaceuticals, Aurora Foundation, Boston Claude D Pepper Older Americans Independence Center, and Boston University's Clinical and Translational Science Institute. PMID- 27377543 TI - Testosterone and the brain: the power of a negative study. PMID- 27377545 TI - Measuring Congestion in Acute Heart Failure: The "Holy Grail" Still Awaits. PMID- 27377546 TI - Why is Mini-Mental state examination performance correlated with estimated premorbid cognitive ability? AB - BACKGROUND: Tests requiring the pronunciation of irregular words are used to estimate premorbid cognitive ability in patients with clinical diagnoses, and prior cognitive ability in normal ageing. However, scores on these word-reading tests correlate with scores on the Mini-Mental State Examination (MMSE), a widely used screening test for possible cognitive pathology. This study aimed to test whether the word-reading tests' correlations with MMSE scores in healthy older people are explained by childhood IQ or education. METHOD: Wechsler Test of Adult Reading (WTAR), National Adult Reading Test (NART), MMSE scores and information about education were obtained from 1024 70-year-olds, for whom childhood intelligence test scores were available. RESULTS: WTAR and NART were positively correlated with the MMSE (r ~ 0.40, p < 0.001). The shared variance of WTAR and NART with MMSE was significantly attenuated by ~70% after controlling for childhood intelligence test scores. Education explained little additional variance in the association between the reading tests and the MMSE. CONCLUSIONS: MMSE, which is often used to index cognitive impairment, is associated with prior cognitive ability. MMSE score is related to scores on WTAR and NART largely due to their shared association with prior ability. Obtained MMSE scores should be interpreted in the context of prior ability (or WTAR/NART score as its proxy). PMID- 27377547 TI - Identification of candidate domestication regions in the radish genome based on high-depth resequencing analysis of 17 genotypes. AB - KEY MESSAGE: This study provides high-quality variation data of diverse radish genotypes. Genome-wide SNP comparison along with RNA-seq analysis identified candidate genes related to domestication that have potential as trait-related markers for genetics and breeding of radish. Radish (Raphanus sativus L.) is an annual root vegetable crop that also encompasses diverse wild species. Radish has a long history of domestication, but the origins and selective sweep of cultivated radishes remain controversial. Here, we present comprehensive whole genome resequencing analysis of radish to explore genomic variation between the radish genotypes and to identify genetic bottlenecks due to domestication in Asian cultivars. High-depth resequencing and multi-sample genotyping analysis of ten cultivated and seven wild accessions obtained 4.0 million high-quality homozygous single-nucleotide polymorphisms (SNPs)/insertions or deletions. Variation analysis revealed that Asian cultivated radish types are closely related to wild Asian accessions, but are distinct from European/American cultivated radishes, supporting the notion that Asian cultivars were domesticated from wild Asian genotypes. SNP comparison between Asian genotypes identified 153 candidate domestication regions (CDRs) containing 512 genes. Network analysis of the genes in CDRs functioning in plant signaling pathways and biochemical processes identified group of genes related to root architecture, cell wall, sugar metabolism, and glucosinolate biosynthesis. Expression profiling of the genes during root development suggested that domestication-related selective advantages included a main taproot with few branched lateral roots, reduced cell wall rigidity and favorable taste. Overall, this study provides evolutionary insights into domestication-related genetic selection in radish as well as identification of gene candidates with the potential to act as trait-related markers for background selection of elite lines in molecular breeding. PMID- 27377548 TI - Use and misuse of common terminology criteria for adverse events in cancer clinical trials. AB - BACKGROUND: Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) were released in 2003 and have been used widely to report toxicity in publications or presentations describing cancer clinical trials. Here we evaluate whether guidelines for reporting toxicity are followed in publications reporting randomized clinical trials (RCTs) for cancer. METHODS: Phase III RCTs evaluating systemic cancer therapy published between 2011 and 2013, were reviewed to identify eligible studies, which stated explicitly that CTCAE v3.0 was used to report toxicity. Each AE term and its grade were located in CTCAE v3.0 to determine if they fell within the guidelines provided in the explanatory file. RESULTS: A total of 166 publications were included in this analysis. Criteria from CTCAE v3.0 were frequently used incorrectly. For example, CATEGORY names such as Metabolic were misreported as AEs in 19 trials, and inappropriate grades for AEs assigned frequently. For example, febrile neutropenia was graded 1 or 2 in 35 of 91 studies (38 %), but the minimum grade for this toxicity is 3. Alopecia was graded 3 or more in 19 of 77 studies (25 %), but the maximum is only grade 2. CONCLUSION: The present study provides evidence of poor reporting of toxicity in clinical trials. The study provides a lower estimate for the misuse of AE terms and grades, and implies that other AE terms and grades that conform to CTCAE v3.0 guidelines may have been assigned incorrectly. Inaccurate reporting of toxicity in clinical trials can lead clinicians to make inappropriate treatment decisions. PMID- 27377549 TI - Results of a pilot cluster randomised trial of the use of a Medication Review Tool for people taking antipsychotic medication. AB - BACKGROUND: Government policy encourages increasing involvement of patients in their long-term care. This paper describes the development and pilot evaluation of a 'Medication Review Tool' designed to assist people to participate more effectively in discussions about antipsychotic drug treatment. METHODS: The Medication Review Tool developed consisted of a form to help patients identify pros and cons of their current antipsychotic treatment and any desired changes. It was associated with a website containing information and links about antipsychotics. For the trial, participants diagnosed with psychotic disorders were recruited from community mental health services. Cluster randomisation was used to allocate health professionals (care co-ordinators) and their associated patients to use of the Medication Review Tool or usual care. All participants had a medical consultation scheduled, and those in the intervention group completed the Medication Review Tool, with the help of their health professional prior to this, and took the completed Form into the consultation. Two follow-up interviews were conducted up to three months after the consultation. The principal outcome was the Decision Self Efficacy Scale (DSES). Qualitative feedback was collected from patients in the intervention group. RESULTS: One hundred and thirty patients were screened, sixty patients were randomised, 51 completed the first follow-up assessment and 49 completed the second. Many patients were not randomised due to the timing of their consultation, and involvement of health professionals was inconsistent. There was no difference between the groups on the DSES (-4.16 95 % CI -9.81, 1.49), symptoms, side effects, antipsychotic doses or patient satisfaction. Scores on the Medication Adherence Questionnaire indicated an increase in participants' reported inclination to adherence in the intervention group (coefficient adjusted for baseline values -0.44; 95 % CI -0.76, -0.11), and there was a small increase in positive attitudes to antipsychotic medication (Drug Attitude Inventory, adjusted coefficient 1.65; 95 % CI -0.09, 3.40). Qualitative feedback indicated patients valued the Tool for identifying both positive and negative aspects of drug treatment. CONCLUSIONS: The trial demonstrated the design was feasible, although challenges included service re configurations and maintaining health professional involvement. Results may indicate a more intensive and sustained intervention is required to facilitate participation in decision-making for this group of patients. TRIAL REGISTRATION: Current controlled trials ISRCTN12055530 , Retrospectively registered 9/12/2013. PMID- 27377550 TI - Selective catalytic two-step process for ethylene glycol from carbon monoxide. AB - Upgrading C1 chemicals (for example, CO, CO/H2, MeOH and CO2) with C-C bond formation is essential for the synthesis of bulk chemicals. In general, these industrially important processes (for example, Fischer Tropsch) proceed at drastic reaction conditions (>250 degrees C; high pressure) and suffer from low selectivity, which makes high capital investment necessary and requires additional purifications. Here, a different strategy for the preparation of ethylene glycol (EG) via initial oxidative coupling and subsequent reduction is presented. Separating coupling and reduction steps allows for a completely selective formation of EG (99%) from CO. This two-step catalytic procedure makes use of a Pd-catalysed oxycarbonylation of amines to oxamides at room temperature (RT) and subsequent Ru- or Fe-catalysed hydrogenation to EG. Notably, in the first step the required amines can be efficiently reused. The presented stepwise oxamide-mediated coupling provides the basis for a new strategy for selective upgrading of C1 chemicals. PMID- 27377551 TI - Erratum to: The prevalence and clinical characteristics of nonradiographic axial spondyloarthritis among patients with inflammatory back pain in rheumatology practices: a multinational, multicenter study. PMID- 27377553 TI - Identification of radical structures on 1-pentamethylbenzyl-3 ethylimidazoliumsilver(I)bromide and 1,3-bis(pentamethylbenzyl)-4,5 dimethylbenzimidazoliumsilver(I)bromide exposed to gamma rays: an EPR study. AB - 1-Pentamethylbenzyl-3-ethylimidazoliumsilver(I)bromide and 1,3 bis(pentamethylbenzyl)-4,5dimethylbenzimidazoliumsilver(I)bromide and their Ag+ complexes were synthesized and their polycrystal forms were produced by recrystallization in dichloromethane/Et2 O solvent system. Structural determinations were carried out by 1 H NMR and 13 C NMR with a Varian 400 NMR system using tetramethylsilane as internal standard and CDCl3 as solvent. The disappearance of acidic N-heterocyclic carbene proton showed the formation of Ag(I) complexes. Also, elemental analyses were carried out. Electron paramagnetic resonance (EPR) measurements were performed to determine the formed radical structure on the samples irradiated at the room temperature for 72 h by using 60 Co-source with dose rate of 0.680 kGy. The EPR measurements were carried out in the temperature range of 200 K-450 K. Identical radicals were determined on the irradiated compounds. It was observed that the shapes of the spectra of the samples were independent of the temperature but, the resonance line intensities changed linearly with the temperature. Also, it was detected that the free radical on the 1-pentamethylbenzyl-3-ethylimidazoliumsilver(I)bromide is not stable compared to that on the 1,3-bis(pentamethylbenzyl) 4,5dimethylbenzimidazoliumsilver(I)bromide. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27377552 TI - Hyper-resting brain entropy within chronic smokers and its moderation by Sex. AB - Cigarette smoking is a chronic relapsing brain disorder, and remains a premier cause of morbidity and mortality. Functional neuroimaging has been used to assess differences in the mean strength of brain activity in smokers' brains, however less is known about the temporal dynamics within smokers' brains. Temporal dynamics is a key feature of a dynamic system such as the brain, and may carry information critical to understanding the brain mechanisms underlying cigarette smoking. We measured the temporal dynamics of brain activity using brain entropy (BEN) mapping and compared BEN between chronic non-deprived smokers and non smoking controls. Because of the known sex differences in neural and behavioral smoking characteristics, comparisons were also made between males and females. Associations between BEN and smoking related clinical measures were assessed in smokers. Our data showed globally higher BEN in chronic smokers compared to controls. The escalated BEN was associated with more years of smoking in the right limbic area and frontal region. Female nonsmokers showed higher BEN than male nonsmokers in prefrontal cortex, insula, and precuneus, but the BEN sex difference in smokers was less pronounced. These findings suggest that BEN mapping may provide a useful tool for probing brain mechanisms related to smoking. PMID- 27377554 TI - Safety and efficacy profile of bioresorbable-polylactide-polymer-biolimus-A9 eluting stents versus durable-polymer-everolimus- and zotarolimus-eluting stents in patients with acute coronary syndrome. AB - BACKGROUND: Comparative data on long-term safety and efficacy of bioresorbable polymer-BES versus durable-polymer-EES/ZES in ACS setting have hitherto been lacking. We sought to assess the safety and efficacy of bioresorbable-polymer biolimus-A9-eluting stents (BES) compared with thin-strut-durable-polymer everolimus- and zotarolimus-eluting stents (EES/ZES) in patients with acute coronary syndrome (ACS) undergoing PCI. METHODS AND RESULTS: Between 2007 and 2012, 1,547 patients were implanted with new-generation drug-eluting stents (DES). Out of these, 369 received BES and 1,178 EES/ZES. The primary endpoint was probable/definite stent thrombosis (ST) while the secondary endpoint was a composite of all-cause death, myocardial infarction (MI), target vessel revascularization (TVR) and definite ST up to 5 years. As stent assignment was not random, we performed a propensity score matching (PSM), with 1:3 ratio, to account for potential confounders. Primary analysis demonstrated no significant differences between both groups for the primary endpoint of ST (BES vs. EES/ZES: 1.6% vs. 1.9%; mean-event-time = 1,797 days vs. 1,795 days, respectively; P = 0.75) and composite safety endpoint (BES vs. EES/ZES: 12.5% vs. 12.9%; mean-event time = 1,631 days vs. 1,620 days, respectively; P = 0.88). Results regarding the 5-year-ST- and safety endpoint remained non-significant after PSM (P = 0.85, P = 0.56; respectively). After stratification based on cardiovascular risk, no difference regarding ST and composite outcome measure has been documented between both stent groups in high-risk- and low-risk patients. The type of stent did neither predict ST (HR 1.11, 95%CI 0.45-2.74, P = 0.82) nor composite safety endpoint (HR 0.93, 95%CI 0.67-1.30, P = 0.69). CONCLUSIONS: Long-term safety and efficacy of bioresorbable-polymer-BES and durable-polymer-EES/ZES appear comparable in patients with ACS. (c) 2016 Wiley Periodicals, Inc. PMID- 27377555 TI - Highly Conductive PEDOT:PSS Films with 1,3-Dimethyl-2-Imidazolidinone as Transparent Electrodes for Organic Light-Emitting Diodes. AB - Highly conductive poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS) films as transparent electrodes for organic light-emitting diodes (OLEDs) are doped with a new solvent 1,3-dimethyl-2-imidazolidinone (DMI) and are optimized using solvent post-treatment. The DMI doped PEDOT: PSS films show significantly enhanced conductivities up to 812.1 S cm(-1) . The sheet resistance of the PEDOT: PSS films doped with DMI is further reduced by various solvent post treatment. The effect of solvent post-treatment on DMI doped PEDOT: PSS films is investigated and is shown to reduce insulating PSS in the conductive films. The solvent posttreated PEDOT: PSS films are successfully employed as transparent electrodes in white OLEDs. It is shown that the efficiency of OLEDs with the optimized DMI doped PEDOT: PSS films is higher than that of reference OLEDs doped with a conventional solvent (ethylene glycol). The results present that the optimized PEDOT: PSS films with the new solvent of DMI can be a promising transparent electrode for low-cost, efficient ITO-free white OLEDs. PMID- 27377556 TI - Diagnosing misspecification of the random-effects distribution in mixed models. AB - It is traditionally assumed that the random effects in mixed models follow a multivariate normal distribution, making likelihood-based inferences more feasible theoretically and computationally. However, this assumption does not necessarily hold in practice which may lead to biased and unreliable results. We introduce a novel diagnostic test based on the so-called gradient function proposed by Verbeke and Molenberghs (2013) to assess the random-effects distribution. We establish asymptotic properties of our test and show that, under a correctly specified model, the proposed test statistic converges to a weighted sum of independent chi-squared random variables each with one degree of freedom. The weights, which are eigenvalues of a square matrix, can be easily calculated. We also develop a parametric bootstrap algorithm for small samples. Our strategy can be used to check the adequacy of any distribution for random effects in a wide class of mixed models, including linear mixed models, generalized linear mixed models, and non-linear mixed models, with univariate as well as multivariate random effects. Both asymptotic and bootstrap proposals are evaluated via simulations and a real data analysis of a randomized multicenter study on toenail dermatophyte onychomycosis. PMID- 27377557 TI - Optimal processes for probabilistic work extraction beyond the second law. AB - According to the second law of thermodynamics, for every transformation performed on a system which is in contact with an environment of fixed temperature, the average extracted work is bounded by the decrease of the free energy of the system. However, in a single realization of a generic process, the extracted work is subject to statistical fluctuations which may allow for probabilistic violations of the previous bound. We are interested in enhancing this effect, i.e. we look for thermodynamic processes that maximize the probability of extracting work above a given arbitrary threshold. For any process obeying the Jarzynski identity, we determine an upper bound for the work extraction probability that depends also on the minimum amount of work that we are willing to extract in case of failure, or on the average work we wish to extract from the system. Then we show that this bound can be saturated within the thermodynamic formalism of quantum discrete processes composed by sequences of unitary quenches and complete thermalizations. We explicitly determine the optimal protocol which is given by two quasi-static isothermal transformations separated by a finite unitary quench. PMID- 27377559 TI - Formation of Curvature Subunit of Carbon in Combustion. AB - Curvature prevalently exists in the world of carbon materials (e.g., fullerenes, buckyl bowls, carbon nanotubes, and onions), but traditional C2-addition mechanisms fail to elucidate the mechanism responsible for the formation of carbon curvature starting from a pentagonal carbon ring in currently available chemical-physical processes such as combustion. Here, we show a complete series of nascent pentagon-incorporating C5-C18 that are online produced in the flame of acetylene-cyclopentadiene-oxygen and in situ captured by C60 or trapped as polycyclic aromatic hydrocarbons for clarifying the growth of the curved subunit of C20H10. A mechanism regarding C1-substitution and C2-addition has been proposed for understanding the formation of curvature in carbon materials, as exemplified by the typical curved molecule containing a single pentagon completely surrounded by five hexagons. The present mechanism, supported by the intermediates characterized by X-ray crystallography as well as NMR, has been experimentally validated for the rational synthesis of curved molecule in the commercially useful combustion process. PMID- 27377558 TI - First Data on Efficacy and Safety of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis and Forced Vital Capacity of <=50 % of Predicted Value. AB - In the Phase III INPULSIS((r)) trials, 52 weeks' treatment with nintedanib reduced decline in forced vital capacity (FVC) versus placebo in patients with idiopathic pulmonary fibrosis (IPF). Patients who completed the INPULSIS((r)) trials could receive nintedanib in an open-label extension trial (INPULSIS((r)) ON). Patients with FVC <50 % predicted were excluded from INPULSIS((r)), but could participate in INPULSIS((r))-ON. In patients with baseline FVC <=50 % and >50 % predicted at the start of INPULSIS((r))-ON, the absolute mean change in FVC from baseline to week 48 of INPULSIS((r))-ON was -62.3 and -87.9 mL, respectively (n = 24 and n = 558, respectively). No new safety signals were identified in INPULSIS((r))-ON compared with INPULSIS((r)). The decline in FVC in INPULSIS((r)) ON in both subgroups by baseline FVC % predicted was similar to that in INPULSIS((r)), suggesting that nintedanib may have a similar effect on disease progression in patients with advanced disease as in less advanced disease. PMID- 27377560 TI - Young coconut water ameliorates depression via modulation of neurotransmitters: possible mechanism of action. AB - In the current era, plants are frequently tested for its antidepressant potential. Therefore young coconut water, a commonly used plant based beverage, was selected to explore its antidepressant potential. Rodents were selected for this study and forced swim test was conducted to explore antidepressant activity. Analysis of brain biogenic amines using high performance liquid chromatography coupled with electrochemical detection and potentiation of noradrenaline toxicity model were also incorporated in this study to demonstrate probable antidepressant mechanism of action. Coconut water was administered orally at the dose of 4 ml/100 g. Young coconut water showed highly significant increase in struggling time (p < 0.001) in forced swim test. This suggests antidepressant effect of young coconut water. In noradrenaline toxicity model, it was observed that young coconut water is not a good adrenergic component as its lethality percentage in this test was observed 0 % unlike imipramine which showed lethality of 100 %. High performance liquid chromatography-electrochemical detection of rodent's brain revealed decline in 5-hydroxytryptamine, noradrenaline and dopamine, with concomitant decline in metabolites 5-hydroxyindoleacetic acid, 3,4 dihydroxyphenylacetic acid, homovanillic acid and increase in 5 hydroxyindoleacetic acid/5-hydroxytryptamine ratio. Findings from the exploration of monoamines suggest antidepressant effect of young coconut water via homeostasis of monoamines synthesis. PMID- 27377562 TI - Knowledge Dissemination of Intimate Partner Violence Intervention Studies Measured Using Alternative Metrics: Results From a Scoping Review. AB - Alternative metrics measure the number of online mentions that an academic paper receives, including mentions in social media and online news outlets. It is important to monitor and measure dispersion of intimate partner violence (IPV) victim intervention research so that we can improve our knowledge translation and exchange (KTE) processes improving utilization of study findings. The objective of this study is to describe the dissemination of published IPV victim intervention studies and to explore which study characteristics are associated with a greater number of alternative metric mentions and conventional citations. As part of a larger scoping review, we conducted a literature search to identify IPV intervention studies. Outcomes included znumber of alternative metric mentions and conventional citations. Fifty-nine studies were included in this study. The median number of alternative metric mentions was six, and the median number of conventional citations was two. Forty-one percent of the studies (24/59) had no alternative metric mentions, and 27% (16/59) had no conventional citations. Longer time since publication was significantly associated with a greater number of mentions and citations, as were systematic reviews and randomized controlled trial designs. The majority of IPV studies receive little to no online attention or citations in academic journals, indicating a need for the field to focus on implementing strong knowledge dissemination plans. The papers receiving the most alternative metric mentions and conventional citations were also the more rigorous study designs, indicating a need to focus on study quality. We recommend using alternative metrics in conjunction with conventional metrics to evaluate the full dissemination of IPV research. PMID- 27377561 TI - Sex differences in the association between stressor-evoked interleukin-6 reactivity and C-reactive protein. AB - Individuals differ consistently in the magnitude of their inflammatory responses to acute stressors, with females often showing larger responses than males. While the clinical significance of these individual differences remains unclear, it may be that greater inflammatory responses relate to increased systemic inflammation and thereby risk for chronic inflammatory disease. Here, we examined whether acute stressor-evoked interleukin (IL)-6 responses associate with resting levels of C-reactive protein (CRP), a marker of systemic inflammation, and whether this association differs by sex. Subjects were 57 healthy midlife adults (30-51years; 33% female; 68% white). Blood was drawn before and 30-min after two mental stress tasks: a multisource interference task and a Stroop color word task. Hierarchical regressions controlling for age, sex, race, and BMI tested whether stressor evoked IL-6 responses were associated with resting CRP and whether this association differed by sex. Results indicated that sex and stressor-evoked IL-6 responses interacted to predict CRP (DeltaR2=0.08, B=-1.33, beta=-0.39, p=0.02). In males, larger stressor-evoked IL-6 responses associated with higher CRP, whereas in females, stressor-evoked IL-6 responses showed a non-significant negative association with CRP. These findings indicate that inflammatory responses to acute stressors associate with resting levels of CRP; however, this association differs by sex. Previous literature suggests that there are sex differences in stressor-evoked IL-6 responses, but this is the first study to show sex differences in the relationship between acute inflammatory responses and systemic inflammation. The contribution of these sex differences to inflammatory disease risk warrants further investigation. PMID- 27377563 TI - Relationships Between Mental Health, Skill Sets, and Violence Perpetration Among Adolescent Girls. AB - This study examines relationships between emotional health, stress management skills, fight-avoidance skills, and two forms of violence perpetration among adolescent girls at high risk for violence involvement. Participants ( n = 253) were 13- to 17-year-old girls enrolled in a randomized controlled trial. The current study was completed with baseline data collected prior to the start of the intervention. Analyses examined self-report outcome measures of physical violence perpetration in the past 6 months (five-item scale, alpha = .79) and relational aggression perpetration in the past 30 days (six-item scale, alpha = .77). Independent variables included baseline measures of self-esteem (four-item scale, alpha = .89), emotional distress (six-item scale, alpha = .89), stress management skills (eight-item scale, alpha = .86), and fight avoidance skills (five-item scale, alpha = .70). Multivariate regression models predicted each form of violence perpetration controlling for age, race/ethnicity, violence victimization, and clustering of participants within clinics. Initial bivariate results showed that stress management skills and fight avoidance skills were inversely and significantly related to perpetration of both relational and physical violence. Emotional distress was related to significantly higher levels of both violence outcomes. In contrast, self-esteem was not significantly related to either violence outcome. Multivariate analyses revealed that stress management skills and fight avoidance skills were significantly protective against perpetration of both relational aggression and physical violence. In conclusion, findings suggest that clinicians providing services to adolescent girls involved in high risk behaviors assess and foster girls' development of stress management and fight avoidance skills to help reduce their risk of involvement in relational violence and physical fighting. PMID- 27377565 TI - Pregnancy and lactation period: Which antibiotic and rinsing solutions? AB - The aim of this paper is to show aspects of dental treatment in pregnancy. The reader should gain security in the election of the proper drugs for antibiotic therapy and rinsing solutions. Antibiotics as penicillins are the first choice in case of dental infections in pregnancy. In allergic patients, macrolides may be an alternative. Wound and mouth rinsing solutions containing chlorhexidine should be preferred in pregnancy. Ledermix((r)) in endodontic treatment should be avoided in the pregnant woman. Solcoseryl((r)) can be used for wound healing. Elective dental procedures should be postponed after delivery and after lactation period. PMID- 27377566 TI - Palladium-Catalyzed Environmentally Benign Acylation. AB - Recent trends in research have gained an orientation toward developing efficient strategies using innocuous reagents. The earlier reported transition-metal catalyzed carbonylations involved either toxic carbon monoxide (CO) gas as carbonylating agent or functional-group-assisted ortho sp(2) C-H activation (i.e., ortho acylation) or carbonylation by activation of the carbonyl group (i.e., via the formation of enamines). Contradicting these methods, here we describe an environmentally benign process, [Pd]-catalyzed direct carbonylation starting from simple and commercially available iodo arenes and aldehydes, for the synthesis of a wide variety of ketones. Moreover, this method comprises direct coupling of iodoarenes with aldehydes without activation of the carbonyl and also without directing group assistance. Significantly, the strategy was successfully applied to the synthesis n-butylphthalide and pitofenone. PMID- 27377564 TI - Phenotypic reversion in fas mutants of Arabidopsis thaliana by reintroduction of FAS genes: variable recovery of telomeres with major spatial rearrangements and transcriptional reprogramming of 45S rDNA genes. AB - Arabidopsis thaliana mutants dysfunctional in the evolutionarily conserved protein complex chromatin assembly factor-1 (CAF-1), which deposits the canonical histone H3 variant H3.1 during DNA synthesis-dependent chromatin assembly, display complex phenotypic changes including meristem and growth alterations, sensitivity to DNA-damaging agents, and reduced fertility. We reported previously that mutants in the FAS1 subunit of CAF-1 progressively lose telomere and 45S rDNA repeats. Here we show that multiple aspects of the fas phenotype are recovered immediately on expression of a reintroduced FAS1 allele, and are clearly independent of the recovery of rDNA copy-numbers and telomeres. In reverted lines, 45S rDNA genes are recovered to diverse levels with a strikingly different representation of their variants, and the typical association of nucleolar organizing region 4 with the nucleolus is perturbed. One of 45S rDNA variants (VAR1), which is silenced in wild-type (WT) plants without mutation history (Col-0 WT), dominates the expression pattern, whereas VAR2 is dominant in Col-0 WT plants. We propose an explanation for the variability of telomere and 45S rDNA repeats associated with CAF-1 function, suggesting that the differences in nuclear partitioning and expression of the rDNA variants in fas mutants and their revertants provide a useful experimental system to study genetic and epigenetic factors in gene dosage compensation. PMID- 27377567 TI - The value of serum pro-oxidant/antioxidant balance in the assessment of asphyxia in term neonates. AB - OBJECTIVE: Asphyxia is a major cause of disabilities in term-born infants. Here we have explored the value in HIE (hypoxic-ischemic-encephalopathy) of using a combination of serum pro-oxidant/antioxidant balance (PAB) assay for predicting the prognosis of asphyxia. METHOD: Ninety term neonates with asphyxia were enrolled and followed up for two years. Serum PAB, demographic/biochemical characteristics of mothers, and their neonates were determined. The Denver II test was used to assess outcomes. RESULTS: Of the 90 asphyxiated neonates, 47 (52.2%) had a normal outcome and 43 babies (47.8%) had abnormal outcome. Serum PAB levels in neonates with normal and abnormal outcomes were 17.1 +/- 9.23 and 48.27 +/- 41.30 HK, respectively. A combination of HIE intensity and PAB, compared to other indicators, had a higher predictive-value (95.2%) for outcomes in asphyxiated babies. CONCLUSION: We demonstrate that PAB in combination with HIE grade may have a better predictive value for the prognosis of asphyxiated babies and predicting future neurologic problems in asphyxiated term infants. PMID- 27377568 TI - Indazole, Pyrazole, and Oxazole Derivatives Targeting Nitric Oxide Synthases and Carbonic Anhydrases. AB - Nitric oxide (NO) is an essential endogenous mediator with a physiological role in the central nervous system as neurotransmitter and neuromodulator. A growing number of studies have demonstrated that abnormal nitrergic signaling is a crucial event in the development of neurodegeneration. In particular, the uncontrolled production of NO by neuronal nitric oxide synthase (nNOS) is observed in several neurodegenerative diseases. Moreover, it is well recognized that specific isoforms of human carbonic anhydrase (hCA) physiologically modulate crucial pathways of signal processing and that low expression of CA affects cognition, leading to mental retardation, Alzheimer's disease, and aging-related cognitive impairments. In light of this, dual agents that are able to target both NOS (inhibition) and CA (activation) could be useful drug candidates for the treatment of Alzheimer's disease, aging, and other neurodegenerative diseases. In the present work, we show the design, synthesis, and in vitro biological evaluation of new nitrogen-based heterocyclic compounds. Among the tested molecules, 2-amino-3-(4-hydroxyphenyl)-N-(1H-indazol-5-yl)propanamide hydrochloride (10 b) was revealed to be a potent dual agent, able to act as a selective nNOS inhibitor and activator of the hCA I isoform. PMID- 27377569 TI - Hydroboration of Phosphaalkynes by HB(C6 F5 )2. AB - The hydroboration of phosphaalkynes with Piers' borane (HB(C6 F5 )2 ) generated unusual phosphaalkenylboranes [RCH=PB(C6 F5 )2 ]2 that persisted as dimers in both solution and the solid state. These P2 B2 heterocycles underwent ring opening when subjected to nucleophiles, such as pyridine and tert butylisocyanide, to yield monomeric phosphaalkenylborane adducts RCH=PB(C6 F5 )2 (L). DFT calculations were performed to probe the nature of the interaction of phosphaalkynes with boranes. PMID- 27377570 TI - HD Flow Cytometry: An Improved Way to Quantify Cellular Interactions with Nanoparticles. AB - Histogram deconvolution flow cytometry enables improved quantification of nanomaterial-cell interactions. The algorithm identifies the positive cells in highly overlapped populations and calculates the fluorescence intensity of the positive population. This technique performs better than commercially available methods with the additional benefit of visualizing the output. PMID- 27377571 TI - The effect of the final irrigant on the antimicrobial activity of root canal sealers. AB - OBJECTIVE: Root canal irrigation is an essential step in root canal therapy as it enables the elimination of microorganisms. The final irrigant may affect the properties of the root canal sealer used during obturation particularly with tricalcium silicate-based sealers, which interact with dentine. The aim of this study was to assess the antimicrobial activity of tricalcium silicate-containing sealers in contact with different irrigants. Furthermore the sealer surface in contact with the irrigant was characterized. METHODOLOGY: The antimicrobial activity of BioRoot RCS, MTA Fillapex and AH Plus in contact with water, ethylenediaminetetracetic acid (EDTA) and phosphate buffered saline (PBS) was assessed by agar diffusion test and by the intratubular infection test against Enterococcus faecalis. The sealer surface in contact with the three solutions was characterized after 1min contact and also after simulation of in vivo sealer contact with irrigating solution inside a tooth model by grazing angle X-ray diffraction analysis. RESULTS: Irrigation with EDTA showed the highest antimicrobial properties of the three root canal sealers followed by water without significant differences. The antimicrobial activity of BioRoot RCS was significantly higher than the other sealers after exposition to the three root canal irrigants followed by MTA Fillapex. AH Plus lost its antimicrobial properties after irrigation with water and PBS. CONCLUSIONS: BioRoot RCS showed the greatest antimicrobial activity. The root canal sealers exerted a higher antimicrobial activity when EDTA was used as final irrigant. PBS may be contraindicated as a final irrigant as it reduces the antimicrobial activity of sealers. PMID- 27377572 TI - Hyaluronic Acid Derivative with Improved Versatility for Processing and Biological Functionalization. AB - A hydrophobic/amino functionalized derivative of hyaluronic acid (HA-EDA-C18 ) has been processed by salt leaching technique as porous scaffold without need of chemical crosslinking. Aim of this work is to demonstrate the improved versatility of HA-EDA-C18 in terms of processing and biological functionalization. In particular, the chemical procedure to tether thiol bearing RGD peptide has been described. Moreover, the possibility to load and to control the release of slightly water soluble effectors has been demonstrated by using dexamethasone. First, the swelling and degradation profiles of the scaffolds have been investigated, then the evaluation of metabolic activity of bovine chondrocytes, the histological analysis, and microscope observations has been performed to evaluate cellular adhesion and proliferation as well as the production of collagen type II. PMID- 27377573 TI - Current updates in catheters, tubes and drains in the pediatric chest: A practical evaluation approach. AB - Chest radiographs are very helpful tool not only in the evaluation of respiratory and/or cardiac pathologies, but also to help clinicians in the assessment of various tubes and catheters inserted in pediatric patients. This review article focuses on the indications, contraindications, ideal locations of the tips of these tubes and catheters, as well as the consequences of malpositioning. Clinical outcomes of pediatric patients can be affected by the placement of these medical devices. The radiologist therefore has a critical role in detecting and relaying such malpositioned devices for prompt revisions or removal. PMID- 27377575 TI - Low 22-item sinonasal outcome test scores in chronic rhinosinusitis: Why do patients seek treatment? AB - OBJECTIVES/HYPOTHESIS: Patients with chronic rhinosinusitis (CRS) who experience minimal reductions in quality of life (QoL) may present for treatment despite QoL scores comparable to controls without CRS. This study seeks to identify cofactors influencing patients with CRS and low 22-item Sinonasal Outcome Test (SNOT-22) scores to seek care. STUDY DESIGN: Prospective, multicenter, observational cohort. METHODS: Patients with CRS were enrolled between April 2011 and September 2015. Patients with sinonasal mucocele or unilateral sinus opacification were excluded. Control subjects without CRS were enrolled for comparison. Low-SNOT CRS was defined as a SNOT-22 score < 20. RESULTS: A total of 774 subjects (low-SNOT CRS, n = 38; high-SNOT CRS, SNOT-22 >= 20, n = 641; controls without CRS, n = 95) were enrolled. Low SNOT scores were identified in 6% of subjects with CRS. After adjustment, low-SNOT CRS and control groups without CRS reported similar baseline average SNOT-22 total scores (P = .879). Unexpectedly, compared to controls, low SNOT CRS patients had significantly better average psychological (2.1 +/- 2.3 vs. 5.8 +/- 6.0; P = .030) and sleep dysfunction (2.7 +/- 3.4 vs. 6.0 +/- 5.2; P = .016) scores. Fourteen of 38 (37%) low-SNOT patients elected to undergo endoscopic sinus surgery (ESS), with a significantly lower likelihood of reporting a minimal clinically important difference (MCID) when compared to high SNOT patients (43% vs. 82%; P < .001) after a mean follow-up of ~15 months. CONCLUSIONS: Low-SNOT CRS patients represent an outlier population for which measures of QoL fail to identify factors influencing the decision to seek treatment. Low-SNOT CRS patients electing ESS have a decreased likelihood of reporting MCIDs following ESS. Further study is required to identify novel factors associated with treatment-seeking behavior in this population. LEVEL OF EVIDENCE: 3B Laryngoscope, 127:22-28, 2017. PMID- 27377576 TI - Blood glucose on admission and mortality in patients with venous thromboembolism. AB - AIMS: Evaluate association between admission blood glucose (ABG) and mortality in patients with or without diabetes mellitus (DM) hospitalized for venous thromboembolism (VTE). METHODS: Observational data derived from the electronic records of hospitalized patients >=18years, admitted for VTE (including deep vein thrombosis and pulmonary embolism) between January 2011 and December 2013. ABG levels were classified to categories: <=70 (low), 70-110 (normal), 111-140 (mildly elevated), 141-180mg/dl (moderately elevated) and>180mg/dl (markedly elevated). Main outcome was all-cause mortality at the end of follow-up. We had complete follow-up data at 12months for all patients; median follow-up time was 1126days. RESULTS: Cohort included 567 patients, 137 with (mean age 73, 45% male), and 430 without DM (mean age 65, 40% male). There was a significant interaction between DM, ABG and mortality (p<=0.05). In patients without DM there was a significant association between ABG and mortality: [hazard ratios 1.6, 2.3, and 4.7 respectively for mildly, moderately and markedly elevated ABG (p<=0.01)]. A significant association between ABG and mortality persisted following multivariable analysis only in patients with markedly elevated ABG (HR=2.3 95% CI 1.2-4.5). Similar results were evident in patients with deep vein thrombosis or pulmonary embolism. In patients with DM there was no significant association between ABG and mortality. CONCLUSION: In patients without DM hospitalized for VTE, markedly elevated ABG is associated with increased mortality. PMID- 27377577 TI - Pilot trial of a parenting and self-care intervention for HIV-positive mothers: the IMAGE program. AB - A pilot study was conducted to assess the effects of the IMAGE pilot intervention (Improving Mothers' parenting Abilities, Growth, and Effectiveness) on mothers living with HIV (MLH). Based on Fisher and Fisher's IMB model [1992. Changing AIDS risk behavior. Psychological Bulletin, 111, 455-474], the intervention focused on self-care and parenting behavior skills of MLH that affect maternal, child, and family outcomes. A randomized pre-test-post-test two-group design with repeated assessments was used. MLH (n = 62) and their children aged 6-14 (n = 62; total N = 124) were recruited for the trial and randomized to the theory-based skills training condition or a standard care control condition. Assessments were conducted at baseline with follow-ups at 3, 6, and 12 months. Maternal, child, and family outcomes were assessed. Results show significant effects of the intervention for improving parenting practices for mothers. The intervention also improved family outcomes, and showed improvements in the parent-child relationship. IMAGE had a positive impact on parenting behaviors, and on maternal, child, and family outcomes. Given MLH can be challenged by their illness and also live in under-resourced environments, IMAGE may be viewed as a viable way to improve quality of life and family outcomes. PMID- 27377578 TI - Reconsidering "Unprotected" and HIV Risk in the Twenty-First Century. PMID- 27377579 TI - Altered resting-state functional organization within the central executive network in obsessive-compulsive disorder. AB - AIM: Obsessive-compulsive disorder (OCD) is associated with deficits in response inhibition and planning, which are governed by the central executive network. The objective of this study was to investigate both intra- and inter-regional resting state connectivity within the central executive network in OCD. METHODS: Thirty OCD patients and 30 matched healthy controls were scanned using resting-state functional magnetic resonance imaging. The independent component analysis was used on a separate sample of healthy controls to generate the central executive network mask for the subsequent OCD analyses. Regional homogeneity (ReHo) and seed-based functional connectivity analyses were used to explore the differences between intra- and inter-regional synchronized activity within the central executive network in OCD patients at rest. RESULTS: Increased ReHo and functional connectivity in the key regions of the central executive network, such as the orbitofrontal cortex, dorsolateral prefrontal cortex, and the angular gyrus, were found in OCD patients. Furthermore, changes in both the ReHo within the orbitofrontal cortex and the functional connectivity between the orbitofrontal cortex and angular gyrus were negatively correlated with OCD duration. CONCLUSION: The increased resting-state functional organization within the central executive network may be related to OCD patients' deficits in cognitive control and symptom progression. PMID- 27377581 TI - Association of the FTO (rs9939609) and MC4R (rs17782313) gene polymorphisms with maternal body weight during pregnancy. AB - OBJECTIVE: The fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) genes have been consistently associated with the risk for obesity, but few studies have examined the association of the obesity risk alleles with gestational outcomes. The aim of this study was to evaluate the association between single nucleotide polymorphisms (SNPs) of the FTO (rs9939609) and MC4R (rs17782313) genes with changes in maternal body weight during pregnancy. METHODS: A sample of 136 pregnant women were followed in a prospective cohort at 5 to 13, 20 to 26, and 30 to 36 wk gestation and 30 to 45 d postpartum. SNPs were analyzed by real-time polymerase chain reaction. Associations between polymorphisms and the outcomes were investigated through longitudinal linear mixed-effects models, multiple linear regression models, and Poisson regression models. RESULTS: An SNP in the FTO (rs9939609) gene but not in the MC4R (rs17782313) gene was significantly associated with prepregnancy body mass index (BMI) >=25 kg/m(2) (relative riskFTO = 2.1; 95% confidence interval [CI], 1.4 3.1). SNPs were not statistically associated with excessive gestational weight gain (GWG) or postpartum weight retention (PPWR). For the FTO (rs9939609) gene, women with the AA genotype were heavier in the body weight trajectory of pregnancy, but not when their weight had been adjusted for prepregnancy BMI (betaFTO = 0.5 kg; 95% CI, -1.9 to 3). These women started pregnancy heavier but gained less weight (FTO*gestational age = -0.1; 95% CI, -0.2 to 0.03) compared with those who had at least one T allele. CONCLUSIONS: The FTO (rs9939609) AA genotype is positively associated with prepregnancy excessive weight. We found no evidence of a significant effect of the MC4R (rs17782313) or the FTO (rs9939609) gene polymorphisms on the GWG and PPWR. PMID- 27377580 TI - Caffeine consumption, insomnia, and sleep duration: Results from a nationally representative sample. AB - OBJECTIVE: Insomnia symptoms have been individually associated with both caffeine consumption and sleep duration abnormalities in prior studies. The goal of this study was to determine whether caffeine consumption was associated with insomnia symptoms from a population perspective and whether this relationship depended on habitual sleep duration. METHODS: Data were extracted from the 2007-2008 National Health and Nutritional Examination Survey (N = 4730). Caffeine consumption was quantified as mg/d from 2 typical days of use, 7 to 10 d apart. Insomnia symptoms were evaluated using frequencies of difficulty falling asleep (DFA), difficulty staying asleep (DSA), non-restorative sleep (NRS), and daytime sleepiness (DS). Habitual sleep duration was assessed as the hours of sleep obtained on a typical night. Binomial logistic regression analysis evaluated the relationships of individual insomnia and sleepiness symptoms (DFA, DSA, NRS, and DS) with caffeine consumption and sleep duration variables, after adjusting for covariates. RESULTS: The mean +/- SD caffeine consumption was 176.6 +/- 201 mg/d. Mean habitual sleep duration was 6.8 +/- 1.4 h. Insomnia symptoms were prevalent in 19.1% to 28.4% of the respondents. Although caffeine consumption was associated with all insomnia symptoms in the unadjusted models, the adjusted models demonstrated a trend toward significance with DSA. Sleep duration was inversely associated with the insomnia symptoms in unadjusted and adjusted analysis. Finally, NRS was associated with an interaction between increased caffeine consumption and sleep duration. CONCLUSION: The association between caffeine use and insomnia symptoms depends on habitual sleep duration at a population level. PMID- 27377582 TI - A path analysis of stress and premenstrual symptoms in Korean international and Korean domestic students. AB - AIMS: To identify the relationships between perceived stress, acculturative stress and premenstrual symptoms, among other associated factors (e.g. depressive symptoms, coping self-efficacy, perceived social support) of premenstrual symptoms suggested in the literature by testing the conceptual framework of the 'Stress and Premenstrual Experience Model: Women in Cultural Transition'. BACKGROUND: Level of perceived stress has been cited as a major influencing factor for women's premenstrual symptoms; however, how these two elements are related, including possible mediators and moderators, remains unclear. DESIGN: A longitudinal causal-comparative web-based study design. METHODS: Data collection occurred between November, 2014 - February, 2015. The convenience sampling method was used to recruit 98 Korean international students and 89 Korean domestic students. Weekly surveys were conducted for 10 weeks to capture women's levels of perceived stress, acculturative stress and premenstrual symptoms from two menstrual cycles. The survey data collected during the premenstrual phase was analysed using path analyses. RESULTS/FINDINGS: The hypothesized pathways based on the conceptual model were partially supported in the study. Depressive symptoms were a partial mediator between perceived stress and premenstrual symptoms and between acculturative stress and symptoms in Korean international students. The perceived social support was a moderator between perceived stress and premenstrual symptoms in Korean domestic students. CONCLUSION: This study proposes a revised conceptual model that will contribute to the understanding of stress and premenstrual symptom severity in women in the acculturation process and concludes with suggestions and implications for future nursing practice and research. PMID- 27377583 TI - Identification of secreted and membrane-bound bat immunoglobulin using a Microchiropteran-specific mouse monoclonal antibody. AB - Bat immunity has received increasing attention because some bat species are being decimated by the fungal disease, White Nose Syndrome, while other species are potential reservoirs of zoonotic viruses. Identifying specific immune processes requires new specific tools and reagents. In this study, we describe a new mouse monoclonal antibody (mAb) reactive with Eptesicus fuscus immunoglobulins. The epitope recognized by mAb BT1-4F10 was localized to immunoglobulin light (lambda) chains; hence, the mAb recognized serum immunoglobulins and B lymphocytes. The BT1-4F10 epitope appeared to be restricted to Microchiropteran immunoglobulins and absent from Megachiropteran immunoglobulins. Analyses of sera and other E. fuscus fluids showed that most, if not all, secreted immunoglobulins utilized lambda light chains. Finally, mAb BT1-4F10 permitted the identification of B cell follicles in splenic white pulp. This Microchiropteran-specific mAb has potential utility in seroassays; hence, this reagent may have both basic and practical applications for studying immune process. PMID- 27377584 TI - CYP1A1 mediates the suppression of major inflammatory cytokines in pulmonary alveolar macrophage (PAM) cell lines caused by Mycoplasma hyponeumoniae. AB - Mycoplasmal pneumonia is a lung infection disease caused by Mycoplasma hyopneumoniae in swine. We previously reported that Cytochrome P450 1A1 (CYP1A1) expression was significantly downregulated in pigs infected with M. hyopneumoniae compared to the healthy controls. In this study, pulmonary alveolar macrophage (PAM) cell lines with CYP1A1 overexpression or siRNA-mediated CYP1A1 silencing were used to explore the biological function and regulatory mechanism of CYP1A1 gene expression changed on the inflammatory response of pigs infected with M. hyopneumoniae. The results showed that the cells overexpressing CYP1A1 infected with M. hyopneumoniae led to a rapid increase in PPAR-gamma expression, which resulted in decreasing the levels of several inflammatory cytokines including IL 1beta, IL-6, IL-8 and TNF-alpha. On the contrary, this effect was just opposite in CYP1A1-RNAi cells infected with M. hyopneumoniae. We suggest that CYP1A1 suppress the inflammatory response caused by M. hyopneumoniae infection, via PPAR gamma signaling pathway in pigs. PMID- 27377585 TI - miR-34a(-/-) mice are susceptible to diet-induced obesity. AB - OBJECTIVE: MicroRNA (miR)-34a regulates inflammatory pathways, and increased transcripts have been observed in serum and subcutaneous adipose of subjects who have obesity and type 2 diabetes. Therefore, the role of miR-34a in adipose tissue inflammation and lipid metabolism in murine diet-induced obesity was investigated. METHODS: Wild-type (WT) and miR-34a(-/-) mice were fed chow or high fat diet (HFD) for 24 weeks. WT and miR-34a(-/-) bone marrow-derived macrophages were cultured in vitro with macrophage colony-stimulating factor (M-CSF). Brown and white preadipocytes were cultured from the stromal vascular fraction (SVF) of intrascapular brown and epididymal white adipose tissue (eWAT), with rosiglitazone. RESULTS: HFD-fed miR-34a(-/-) mice were significantly heavier with a greater increase in eWAT weight than WT. miR-34a(-/-) eWAT had a smaller adipocyte area, which significantly increased with HFD. miR-34a(-/-) eWAT showed basal increases in Cd36, Hmgcr, Lxralpha, Pgc1alpha, and Fasn. miR-34a(-/-) intrascapular brown adipose tissue had basal reductions in c/ebpalpha and c/ebpbeta, with in vitro miR-34a(-/-) white adipocytes showing increased lipid content. An F4/80(high) macrophage population was present in HFD miR-34a(-/-) eWAT, with increased IL-10 transcripts and serum IL-5 protein. Finally, miR-34a( /-) bone marrow-derived macrophages showed an ablated CXCL1 response to tumor necrosis factor-alpha. CONCLUSIONS: These findings suggest a multifactorial role of miR-34a in controlling susceptibility to obesity, by regulating inflammatory and metabolic pathways. PMID- 27377586 TI - Brain-resident memory T cells represent an autonomous cytotoxic barrier to viral infection. AB - Tissue-resident memory T cells (TRM) persist at sites of prior infection and have been shown to enhance pathogen clearance by recruiting circulating immune cells and providing bystander activation. Here, we characterize the functioning of brain-resident memory T cells (bTRM) in an animal model of viral infection. bTRM were subject to spontaneous homeostatic proliferation and were largely refractory to systemic immune cell depletion. After viral reinfection in mice, bTRM rapidly acquired cytotoxic effector function and prevented fatal brain infection, even in the absence of circulating CD8(+) memory T cells. Presentation of cognate antigen on MHC-I was essential for bTRM-mediated protective immunity, which involved perforin- and IFN-gamma-dependent effector mechanisms. These findings identify bTRM as an organ-autonomous defense system serving as a paradigm for TRM functioning as a self-sufficient first line of adaptive immunity. PMID- 27377588 TI - CD6 modulates thymocyte selection and peripheral T cell homeostasis. AB - The CD6 glycoprotein is a lymphocyte surface receptor putatively involved in T cell development and activation. CD6 facilitates adhesion between T cells and antigen-presenting cells through its interaction with CD166/ALCAM (activated leukocyte cell adhesion molecule), and physically associates with the T cell receptor (TCR) at the center of the immunological synapse. However, its precise role during thymocyte development and peripheral T cell immune responses remains to be defined. Here, we analyze the in vivo consequences of CD6 deficiency. CD6( /-) thymi showed a reduction in both CD4(+) and CD8(+) single-positive subsets, and double-positive thymocytes exhibited increased Ca(2+) mobilization to TCR cross-linking in vitro. Bone marrow chimera experiments revealed a T cell autonomous selective disadvantage of CD6(-/-) T cells during development. The analysis of TCR-transgenic mice (OT-I and Marilyn) confirmed that abnormal T cell selection events occur in the absence of CD6. CD6(-/-) mice displayed increased frequencies of antigen-experienced peripheral T cells generated under certain levels of TCR signal strength or co-stimulation, such as effector/memory (CD4(+)TEM and CD8(+)TCM) and regulatory (T reg) T cells. The suppressive activity of CD6(-/-) T reg cells was diminished, and CD6(-/-) mice presented an exacerbated autoimmune response to collagen. Collectively, these data indicate that CD6 modulates the threshold for thymocyte selection and the generation and/or function of several peripheral T cell subpopulations, including T reg cells. PMID- 27377587 TI - Genetically distinct leukemic stem cells in human CD34- acute myeloid leukemia are arrested at a hemopoietic precursor-like stage. AB - Our understanding of the perturbation of normal cellular differentiation hierarchies to create tumor-propagating stem cell populations is incomplete. In human acute myeloid leukemia (AML), current models suggest transformation creates leukemic stem cell (LSC) populations arrested at a progenitor-like stage expressing cell surface CD34. We show that in ~25% of AML, with a distinct genetic mutation pattern where >98% of cells are CD34(-), there are multiple, nonhierarchically arranged CD34(+) and CD34(-) LSC populations. Within CD34(-) and CD34(+) LSC-containing populations, LSC frequencies are similar; there are shared clonal structures and near-identical transcriptional signatures. CD34(-) LSCs have disordered global transcription profiles, but these profiles are enriched for transcriptional signatures of normal CD34(-) mature granulocyte macrophage precursors, downstream of progenitors. But unlike mature precursors, LSCs express multiple normal stem cell transcriptional regulators previously implicated in LSC function. This suggests a new refined model of the relationship between LSCs and normal hemopoiesis in which the nature of genetic/epigenetic changes determines the disordered transcriptional program, resulting in LSC differentiation arrest at stages that are most like either progenitor or precursor stages of hemopoiesis. PMID- 27377590 TI - Toxicity of Bacillus thuringiensis crystal proteins against eri silkworm, Samia cynthia ricini (Lepidoptera: Saturniidae). AB - Ten purified crystal proteins of Bacillus thuringiensis (Bt) were tested at concentrations ranging from 2.93 to 3000ng/cm(2) for their toxicity to eri silkworm through protein paint bioassays using castor leaves. Based on LC50 values, Cry1Aa (2.6ng/cm(2)) was highly toxic followed by Cry1Ac (29.3ng/cm(2)) and Cry1Ab (68.7ng/cm(2)). The Cry1Ca and Cry1Ea proteins were moderately toxic to eri silkworm larvae and resulted in 23% and 28% mortality, respectively at the highest concentration tested (3000ng/cm(2)). Only reduction in larval weight was observed with Cry2Aa, Cry1Da and Cry9Aa proteins while Cry3Aa and Cry1Ba proteins were found to be nontoxic. PMID- 27377591 TI - Pelvic Exenteration: Surgical Aspects and Analysis of Early and Late Morbidity in a Series of 106 Patients. AB - INTRODUCTION: The aim of this study was to report the surgical results in a series of pelvic exenterations, its peroperative difficulties, postoperative complications, mortality and long-term complications. PATIENTS AND METHODS: Between November 1980 and December 2008, pelvic exenteration with curative intent has been performed in 106 patients, 87 female and 19 male, for gynecologic malignancy in 69, intestinal tumors in 29, urologic in 6 and advanced skin carcinomas in 2. The exenteration was performed as primary treatment in only 21 patients, in the others it was for persistent or recurrent tumors after radiotherapy and/or surgery. RESULTS: In 86 patients a total exenteration was performed and in 55 the resection involved an extension beyond the classical planes of dissection. An incontinent urinary diversion was made in 100 patients, a colo-anal anastomis in 35, omentoplasty was standard and muscle flaps were used in 15 patients. Blood loss necessitating transfusion of more than 10 packed cell units or gauze packing did occur in 27 patients with extended resection. Postoperative complications occurred in 64 patients necessitating relaparotomy in 14. Mortality within 30 days was 2%, in hospital 5% but did not occur in the last 44 patients. During the very long follow-up serious late complications were observed in the kidneys of 12 patients and in the small bowel of 5. CONCLUSIONS: Pelvic exenteration is still a major surgical undertaking with a 60% complication rate but can nowadays be performed with a low mortality. Postoperative complications were related to radiotherapy dose above 50 Gy, extension of dissection, the empty pelvis, the urinary diversion and the small intestine. A protected colo-anal anastomosis should be offered when the pelvic floor can be conserved and muscle flaps should be considered after total infralevatoric exenteration. Bricker's urinary diversion still is the golden standard. Long-term complications were observed in 40 patients requiring surgery in 19. PMID- 27377589 TI - Siglec-H protects from virus-triggered severe systemic autoimmunity. AB - It is controversial whether virus infections can contribute to the development of autoimmune diseases. Type I interferons (IFNs) are critical antiviral cytokines during virus infections and have also been implicated in the pathogenesis of systemic lupus erythematosus. Type I IFN is mainly produced by plasmacytoid dendritic cells (pDCs). The secretion of type I IFN of pDCs is modulated by Siglec-H, a DAP12-associated receptor on pDCs. In this study, we show that Siglec H-deficient pDCs produce more of the type I IFN, IFN-alpha, in vitro and that Siglec-H knockout (KO) mice produce more IFN-alpha after murine cytomegalovirus (mCMV) infection in vivo. This did not impact control of viral replication. Remarkably, several weeks after a single mCMV infection, Siglec-H KO mice developed a severe form of systemic lupus-like autoimmune disease with strong kidney nephritis. In contrast, uninfected aging Siglec-H KO mice developed a mild form of systemic autoimmunity. The induction of systemic autoimmune disease after virus infection in Siglec-H KO mice was accompanied by a type I IFN signature and fully dependent on type I IFN signaling. These results show that Siglec-H normally serves as a modulator of type I IFN responses after infection with a persistent virus and thereby prevents induction of autoimmune disease. PMID- 27377592 TI - Climate threat on the Macaronesian endemic bryophyte flora. AB - Oceanic islands are of fundamental importance for the conservation of biodiversity because they exhibit high endemism rates coupled with fast extinction rates. Nowhere in Europe is this pattern more conspicuous than in the Macaronesian biogeographic region. A large network of protected areas within the region has been developed, but the question of whether these areas will still be climatically suitable for the globally threatened endemic element in the coming decades remains open. Here, we make predictions on the fate of the Macaronesian endemic bryophyte flora in the context of ongoing climate change. The potential distribution of 35 Macaronesian endemic bryophyte species was assessed under present and future climate conditions using an ensemble modelling approach. Projections of the models under different climate change scenarios predicted an average decrease of suitable areas of 62-87% per species and a significant elevational increase by 2070, so that even the commonest species were predicted to fit either the Vulnerable or Endangered IUCN categories. Complete extinctions were foreseen for six of the studied Macaronesian endemic species. Given the uncertainty regarding the capacity of endemic species to track areas of suitable climate within and outside the islands, active management associated to an effective monitoring program is suggested. PMID- 27377593 TI - The versatility of profunda femoral artery perforator flap for oncological reconstruction after cancer resection-Clinical cases and review of literature. AB - BACKGROUND: The profunda feomris artery perforator (PAP) flap was recently revisited and gains popularity as an alternative method of autologous breast reconstruction. The purpose of this article is to demonstrate that PAP flap can be used reliably for reconstruction of various soft tissue defects. METHODS: A total of 55 free PAP flaps and 16 pedicle PAP flaps were transferred in 63 patients. Each case was reviewed to verify a PAP flap was performed identifying defect location, flap size, flap design, and postoperative complications. RESULTS: Seven flaps in five patients underwent breast reconstructions, 48 patients underwent head and neck reconstructions using free PAP flaps. The mean perforator number was 1.9, and the average pedicles length was 9.7 cm. The majority of perforators were musculocutaneous, and the others were septocutaneous. The mean ischemia time was 121.4 min. Minor complications included wound poor healing, flap partial necrosis, and pedicle vessels problems. Sixteen pedicle PAP flaps were transferred in 10 patients for vulvar reconstruction. Minor complications included urinary tract infection, poor wound healing, wound infection, hematoma. CONCLUSIONS: The anatomy and number of perforators of PAP flap are reliable with adequate pedicle length. This flap can be an excellent option for reconstruction of most soft tissue defects. J. Surg. Oncol. 2016;114:193-201. (c) 2016 Wiley Periodicals, Inc. PMID- 27377594 TI - Rb silencing mediated by the down-regulation of MeCP2 is involved in cell transformation induced by long-term exposure to hydroquinone. AB - Hydroquinone (HQ), a metabolite of benzene, is a well-known human carcinogen; however, its molecular mechanisms of action remain unclear. MeCP2 has been traditionally described as a transcriptional repressor, though growing evidence indicates that it also activates gene expression. Here, we investigated whether some epigenetic machinery genes are aberrantly expressed as target tumor suppressor genes in HQ-transformed TK6 lymphoblastoid cells. Our results showed that treatment with 5-Aza-2'-deoxycytidine or trichostatin A enhanced the expression of Rb, resulting in cell arrest in G1-phase, and subsequently, an increase in apoptosis and a decrease in cell growth. Moreover, we hypothesised that Rb was silenced by the down-regulation of MeCP2 in HQ-transformed cells, resulting in the dynamic expression of Rb and epigenetic machinery proteins in HQ transformed cells at different time points. The expression of Rb and MeCP2 in patients with B-cell non-Hodgkin's lymphoma (B-NHL) showed that positive staining for MeCP2 or Rb was significantly lower in B-NHL tumor tissues, and these changes were significantly and negatively correlated with the grade of B-NHL. The restoration of MeCP2 in HQ-transformed cells enhanced the expression of Rb, promoted cell apoptosis, and inhibited cell growth. The changes in the expression patterns of MeCP2 and Rb were inversely correlated with the degree of DNA methylation. A ChiP assay revealed that MeCP2 proteins were recruited to the Rb promoter with lower 5'-methylcytosine levels. In conclusion, we demonstrated that the down-regulation of MeCP2 silences Rb, a process involved in cell transformation resulting from long-term exposure to HQ. (c) 2016 Wiley Periodicals, Inc. PMID- 27377595 TI - Gender Differences in Child Aggression: Relations With Gender-Differentiated Parenting and Parents' Gender-Role Stereotypes. AB - This longitudinal study examines the association between child gender and child aggression via parents' physical control, moderated by parents' gender-role stereotypes in a sample of 299 two-parent families with a 3-year-old child in the Netherlands. Fathers with strong stereotypical gender-role attitudes and mothers were observed to use more physical control strategies with boys than with girls, whereas fathers with strong counterstereotypical attitudes toward gender roles used more physical control with girls than with boys. Moreover, when fathers had strong attitudes toward gender roles (stereotypical or counterstereotypical), their differential treatment of boys and girls completely accounted for the gender differences in children's aggressive behavior a year later. Mothers' gender-differentiated parenting practices were unrelated to gender differences in child aggression. PMID- 27377596 TI - Transnuclear CD8 T cells specific for the immunodominant epitope Gra6 lower acute phase Toxoplasma gondii burden. AB - We generated a CD8 T-cell receptor (TCR) transnuclear (TN) mouse specific to the Ld -restricted immunodominant epitope of GRA6 from Toxoplasma gondii as a source of cells to facilitate further investigation into the CD8 T-cell-mediated response against this pathogen. The TN T cells bound Ld -Gra6 tetramer and proliferated upon unspecific and peptide-specific stimulation. The TCR beta sequence of the Gra6-specific TN CD8 T cells is identical in its V- and J-region to the TCR-beta harboured by a hybridoma line generated in response to Gra6 peptide. Adoptively transferred Gra6 TN CD8 T cells proliferated upon Toxoplasma infection in vivo and exhibited an activated phenotype similar to host CD8 T cells specific to Gra6. The brain of Toxoplasma-infected mice carried Gra6 TN cells already at day 8 post-infection. Both Gra6 TN mice as well as adoptively transferred Gra6 TN cells were able to significantly reduce the parasite burden in the acute phase of Toxoplasma infection. Overall, the Gra6 TN mouse represents a functional tool to study the protective and immunodominant specific CD8 T-cell response to Toxoplasma in both the acute and the chronic phases of infection. PMID- 27377598 TI - Identification of a novel mutation of the PRKAR1A gene in a patient with Carney complex with significant osteoporosis and recurrent fractures. AB - OBJECTIVE: Carney complex (CNC) is a rare autosomal dominant multiple neoplasia syndrome characterized by the presence of endocrine and non-endocrine tumors. More than 125 different germline mutations of the protein Kinase A type 1-alpha regulatory subunit (PRKAR1A) gene have been reported. We present a novel PRKAR1A gene germline mutation in a patient with severe osteoporosis and recurrent vertebral fractures. DESIGN: Clinical case report. CASE REPORT: A 53-year-old male with a medical history of surgically removed recurrent cardiac myxomas was evaluated for repeated low-pressure vertebral fractures and severe osteoporosis. Physical examination revealed spotty skin pigmentation of the lower extremities and papules in the nuchal and thoracic region. The presence of hypercortisolism due to micronodular adrenal disease and the history of cardiac myxomas suggested the diagnosis of CNC; the patient underwent detailed imaging investigation and genetic testing. METHODS: Standard imaging and clinical testing; DNA was sequenced by the Sanger method. RESULTS: Sequence analysis from peripheral lymphocytes DNA revealed a novel heterozygous point mutation at codon 172 of exon 2 (c.172G>T) of the PRKAR1A gene, resulting in early termination of the PRKAR1A transcript [p.Glu58Ter (E58X)]. CONCLUSION: We report a novel point mutation of the PRKAR1A gene in a patient with CNC who presented with significant osteoporosis and fractures. Low bone mineral density along with recurrent myxomas should point to the diagnosis of CNC. PMID- 27377597 TI - Corticotropin-releasing factor (CRF) system localization in human fetal heart. AB - OBJECTIVE: The corticotropin-releasing factor (CRF) family consists of the neuropeptides CRF, Ucn I, II and III and the binding sites CRFR1, CRFR2 and CRF BP. It regulates stress response and the homeostasis of an organism. In this study, we examined the presence of the CRF system in the human hearts of normal and pathological fetuses. DESIGN: Heart tissues from 40 archival human fetuses were divided into Group A (without pathology, 'normal'), Group B (with chromosomal abnormalities) and Group C (with congenital disorders). Immunohistochemistry was used to localize the CRF system. Results correlated to gestational trimester and pathology. RESULTS: Immunoreactivity for all antigens was found in cardiac myocytes of all groups, in almost all samples, except Ucn III which was present in almost half of the fetuses of Groups B and C and was not detected at all in Group A. Ucn III was more often present during the earlier stage of development (<21weeks) and in fetuses with congenital disorders. In a fetus diagnosed with heart pathology, all but Ucn III antigens were also present. CONCLUSIONS: We localized a complete CRF system in the human fetal heart and correlated the presence of Ucn III to development and pathology. More studies are needed to verify and clarify the exact role of the CRF system in the human fetal heart. PMID- 27377599 TI - A Dewetting-Induced Assembly Strategy for Precisely Patterning Organic Single Crystals in OFETs. AB - Simple methods for patterning single crystals are critical to fully realize their applications in electronics. However, traditional vapor and solution methods are deficient in terms of crystals with random spatial and quality distributions. In this work, we report a dewetting-induced assembly strategy for obtaining large scale and highly oriented organic crystal arrays. We also demonstrate that organic field-effect transistors (OFETs) fabricated from patterned n-alkyl substituted tetrachloroperylene diimide (R-4ClPDI) single crystals can reach a maximum mobility of 0.65 cm(2) V(-1) s(-1) for C8-4ClPDI in ambient conditions. This technique constitutes a facile method for fabricating OFETs with high performances for large-scale electronics applications. PMID- 27377600 TI - Co-Adaptation Is Key to Coexisting with Large Carnivores. AB - There is a pressing need to integrate large carnivore species into multi-use landscapes outside protected areas. However, an unclear understanding of coexistence hinders the realization of this goal. Here, we provide a comprehensive conceptualization of coexistence in which mutual adaptations by both large carnivores and humans have a central role. PMID- 27377601 TI - Science Communication Through Art: Objectives, Challenges, and Outcomes. AB - The arts are becoming a favored medium for conveying science to the public. Tracking trending approaches, such as community-engaged learning, alongside challenges and goals can help establish metrics to achieve more impactful outcomes, and to determine the effectiveness of arts-based science communication for raising awareness or shaping public policy. PMID- 27377602 TI - Coexistence with Large Carnivores Informed by Community Ecology. AB - Conserving predators on an increasingly crowded planet brings very difficult challenges. Here, we argue that community ecology theory can help conserve these species in human-dominated landscapes. Letting humans and predators share the same landscapes is similar to maintaining a community of predatory species, one of which is humans. PMID- 27377603 TI - Corrigendum to "Results of hepatic and renal function tests to different CO2 pneumoperitoneum conditions: An experimental capnoperitoneum study in dogs" [Res. Vet. Sci. 101 (August 2015) 1-5]. PMID- 27377604 TI - Cardiovascular effects of dexmedetomidine, with or without MK-467, following intravenous administration in cats. AB - OBJECTIVE: To characterize the cardiovascular effects of dexmedetomidine, with or without MK-467, following intravenous (IV) administration in cats. STUDY DESIGN: Prospective Latin square experimental study. ANIMALS: Six healthy adult purpose bred cats. METHODS: Cats were anesthetized with desflurane in oxygen for instrumentation with a carotid artery catheter and a thermodilution catheter in the pulmonary artery. One hour after discontinuation of desflurane, cats were administered dexmedetomidine (25 MUg kg-1), MK-467 (600 MUg kg-1), or dexmedetomidine (25 MUg kg-1) and MK-467 (600 MUg kg-1). All treatments were administered IV as a bolus. Cardiovascular variables were measured prior to drug administration and for 8 hours thereafter. Only data from the dexmedetomidine and dexmedetomidine-MK-467 treatments were analyzed. RESULTS: Dexmedetomidine produced significant decreases in heart rate, cardiac index and right ventricular stroke work index, and significant increases in arterial blood pressure, central venous pressure, pulmonary artery pressure and systemic vascular resistance index. Dexmedetomidine combined with MK-467 resulted in significant but transient decrease in blood pressure and right ventricular stroke work index. CONCLUSION AND CLINICAL RELEVANCE: Following IV co-administration, MK-467 effectively attenuated dexmedetomidine-induced cardiovascular effects in cats. The drug combination resulted in transient reduction in arterial blood pressure, without causing hypotension. PMID- 27377605 TI - Topotactic Conversion of Copper(I) Phosphide Nanowires for Sensitive Electrochemical Detection of H2O2 Release from Living Cells. AB - In this work, we clearly demonstrate for the first time the use of transition metal phosphides to set up a new cathodic analysis platform for sensitive and selective electrochemical nonenzymatic detection of H2O2. With the help of a facile topotactic conversion method, the noble metal-free electrocatalyst of copper(I) phosphide nanowires on three-dimensional porous copper foam (Cu3P NWs/CF) is fabricated with electrochemical anodized Cu(OH)2 NWs as precursor. The Cu3P NWs/CF-based sensor presents excellent electrocatalytic activity for H2O2 reduction with a detection limit of 2 nM, the lowest detection limit achieved by noble-metal free electrocatalyst, which guarantees the possibility of sensitive and reliable detection of H2O2 release from living tumorigenic cells, thus showing the potential application as a sensitive cancer cell detection probe. PMID- 27377606 TI - Thin Ice Films at Mineral Surfaces. AB - Ice films formed at mineral surfaces are of widespread occurrence in nature and are involved in numerous atmospheric and terrestrial processes. In this study, we studied thin ice films at surfaces of 19 synthetic and natural mineral samples of varied structure and composition. These thin films were formed by sublimation of thicker hexagonal ice overlayers mostly produced by freezing wet pastes of mineral particles at -10 and -50 degrees C. Vibration spectroscopy revealed that thin ice films contained smaller populations of strongly hydrogen-bonded water molecules than in hexagonal ice and liquid water. Thin ice films at the surfaces of the majority of minerals considered in this work [i.e., metal (oxy)(hydr)oxides, phyllosilicates, silicates, volcanic ash, Arizona Test Dust] produced intense O-H stretching bands at ~3400 cm(-1), attenuated bands at ~3200 cm(-1), and liquid-water-like bending band at ~1640 cm(-1) irrespective of structure and composition. Illite, a nonexpandable phyllosilicate, is the only mineral that stabilized a form of ice that was strongly resilient to sublimation in temperatures as low as -50 degrees C. As mineral-bound thin ice films are the substrates upon which ice grows from water vapor or aqueous solutions, this study provides new constraints from which their natural occurrences can be understood. PMID- 27377607 TI - SXR rs3842689: a prognostic factor for steroid sensitivity or resistance in pediatric idiopathic nephrotic syndrome. AB - AIM: of the study was to analyse the impact of SXR rs3842689 polymorphism on the response to corticosteroids in pediatric idiopathic nephrotic syndrome. PATIENTS & METHODS: 66 children (56 steroid-sensitive, ten steroid-resistant) were studied for SXR gene polymorphism distribution. RESULTS: Steroid sensitive patients accounted for 96% of cases with In/In polymorphism, but only for 53% of cases with Del/Del polymorphism At odds ratio analysis, Del/Del represented a clear risk factor of steroid resistance (OR: 20.57; p = 0.009), while In/In was a favourable prognostic factor of steroid sensitivity. CONCLUSION: The analysis of SXR polymorphism is a promising tool to predict both the favourable response to corticosteroids and the risk of developing steroid resistance. PMID- 27377608 TI - Ground and excited state interactions of metalloporphyrin PtTMPyP4 with polynucleotides [poly(dG-dC)]2 and [poly(dA-dT)]2. AB - The ground- and excited-state interactions of Pt(ii) meso-tetrakis(4-N methylpyridyl)porphyrin (PtTMPyP4) with polynucleotides [poly(dG-dC)]2 and [poly(dA-dT)]2 have been investigated using UV/visible, circular dichroism, and steady-state and time-resolved emission spectroscopy. PtTMPyP4 intercalates into [poly(dG-dC)]2 with K~ 10(6) M(-1). When bound to [poly(dG-dC)]2 in aerated solution there is a six-fold emission enhancement with 18 nm red-shift in emission maximum. Emission lifetimes are biexponential. In the presence of [poly(dA-dT)]2 at least two distinct groove-binding modes are observed, depending on the binding ratio. In [poly(dA-dT)]2 the emission intensity increases by a maximum factor of 17 with no shift in the emission spectrum. Three exponentials were required for lifetime fitting. The lower extent of emission enhancement in the presence of [poly(dG-dC)]2 suggests that a slow electron transfer may take place to guanine, which is significantly less efficient than that previously observed for PtTMPyP4 in the presence of guanosine 5'-monophosphate (GMP). The results are compared to those previously recorded with free base H2TMPyP4. PMID- 27377609 TI - The Evolving Field of Wound Measurement Techniques: A Literature Review. AB - OBJECTIVE: Wound healing is a complex and multifactorial process that requires the involvement of a multidisciplinary approach. Methods of wound measurement have been developed and continually refined with the purpose of ensuring precision in wound measurement and documentation as the primary indicator of healing. This review aims to ascertain the efficacies of current wound area measurement techniques, and to highlight any perceived gaps in the literature so as to develop suggestions for future studies and practice. METHODS: Med- line, PubMed, CliniKey, and CINAHL were searched using the terms "wound/ulcer measurement techniques," "wound assessment," "digi- tal planimetry," and "structured light." Articles between 2000 and 2014 were selected, and secondary searches were carried out by exam- ining the references of relevant articles. Only papers written in English were included. RESULTS: A universal, standardized method of wound as- sessment has not been established or proposed. At present, techniques range from the simple to the more complex - most of which have char- acteristics that allow for applicability in both rural and urban settings. Techniques covered are: ruler measurements, acetate tracings/contact planimetry, digital planimetry, and structured light devices. Conclu- sion. In reviewing the literature, the precision and reliability of digital planimetry over the more conventional methods of ruler measurements and acetate tracings are consistently demonstrated. The advent and utility of the laser or structured light approach, however, is promising, has only been analyzed by a few, and opens up the scope for further evaluation of this technique. PMID- 27377610 TI - Femoral Vein Cannulation in the Treatment of Osteomyelitis. AB - OBJECTIVE: The main objective was to investigate the feasibil- ity of using the femoral vein for long-term venous access. This was accomplished in the course of treating osteomyelitis patients, using a combination of long-term (6 weeks), outpatient, intravenous (IV) an- tibiotics administered through a femoral central line. This was com- bined subsequently with the use of hyperbaric oxygen (HBO) therapy. Using the femoral vein for central venous access means there is no risk of creating an iatrogenic pneumothorax, which would prohibit the subsequent use of HBO therapy. In addition, the propitious nature of the groin skin flora, Propionibacteriaceae, seems less inclined to par- ticipate in biofilm production, the root cause of central line infections. METHODS: The femoral central lines were all inserted in the operating room (OR) and handled like a regular outpatient surgery with a me- ticulous skin prep completed by experienced OR nurses. Experienced technicians assisted with the surgery. After insertion, the lines were then specially secured to prevent sliding. Vancomycin was adminis- tered preoperatively. RESULTS: Surprisingly, femoral lines placed in this way remained free of infection for up to 70 days. Eight patients with Wagner stage 2 ulcers and underlying osteomyelitis were treated with a course of 6 weeks of vancomycin, followed by HBO therapy. A cure rate of 75% was achieved. CONCLUSION: Femoral vein cannulation for antibi- otic administration is safe and effective in treating patients with osteo- myelitis. The lines should be placed in the OR with the help of skilled personnel. Femoral cannulation avoids the risk of pneumothorax, and the lines can be used for up to 70 days. By avoiding pneumothorax, the patients remain candidates for HBO therapy. PMID- 27377611 TI - Reliability Assessment of an Innovative Wound Score. AB - The authors describe an innovative wound score and demonstrate its versatility for scoring a variety of wound types in addition to diabetic foot ulcers (DFUs). To further test its merits, they determined its interobserver reliability in a prospective series of patients. The Wound Score system the authors created integrates the most important features of 4 predominantly used wound scoring systems. It utilizes a logical 0 to 10 format based on 5 assessments each graded from 2 (best) to 0 (worst). The versatility and reliability of the Wound Score were studied in a prospective series of 94 patients with lower extremity wounds. The Wound Score was quick to determine, applicable to a variety of wound types and locations, and highly objective for grading the severity of each of the 5 assessments. The Wound Score categorized wound types as "healthy," "problem," or "futile" for evaluation and management. Diabetes was present in 75.9%, with 70% of the DFUs scoring in the "problem" wound range. Interobserver reli- ability was high (r = 0.81). The objectivity, versatility, and reliability of the Wound Score system facilitates making decisions about the management of wounds, whether DFUs or not, and provides quantification for compara- tive effectiveness research for wound management. PMID- 27377612 TI - Evidence Corner: Evidence-based Care for Malignant Wounds. AB - Malignant fungating wounds occur in 5% to 10% of individuals with cancer.1 They arise "when malignant tumour cells infiltrate and erode through the skin."2 Guidelines for treating these malignant wounds (MW) often lack randomized, clinical trial (RCT) evidence supporting local wound care interventions that meet patients' physical or psychosocial needs or facilitate healing.3 The rarity of RCTs exploring healing of MWs likely results from their very low expectation of complete closure.1 Affected patients and their professional and family caregivers rate pain, infection, and odor management among the most important challenges in minimizing distress.4-6 Though a recently updated Cochrane review3 reminds us that evidence remains insufficient for firm conclusions supporting management of MW, it does cite 2 recent RCTs described herein7,8 that can serve as "current best evidence"9 to inform clinical decisions for alleviating some aspects of these patients' distress. PMID- 27377613 TI - VAC Therapy Direct to the Medullary Cavity for Chronic Tibial Osteomyelitis. AB - BACKGROUND: Vacuum-assisted wound closure (VAC) is useful for difficult wound beds, although sites where bleeding or infection is expected are usually regarded as problematic for this therapy. This report outlines the treatment of chronic tibial osteomyelitis (Cierny- Mader type III) due to mixed infection with Nocardia spp and Bacteroi- des fragilis by postoperative VAC therapy direct to the medullary cavity, followed by wound coverage with a gastrocnemius myocutaneous skin flap. CASE REPORT: A 64-year-old man developed chronic left tibial os- teomyelitis after a work injury. The nonviable tissues were debrided, including a sequestrum. Nocardia spp and B. fragilis were isolated from surgical bone specimens, and chronic tibial osteomyelitis due to mixed infection was diagnosed. Postoperatively, VAC therapy was performed directly to the open medullary cavity of the tibia and sub- sequently covered the residual soft tissue defect with a gastrocnemius myocutaneous flap. DISCUSSION: The authors could not find any English literature on VAC therapy direct to the medullary cavity combined with transplantation of a myocutaneous flap for osteomyelitis. Nocardia spp can cause a variety of infections, among which osteomyelitis occupies a relatively small percentage. CONCLUSION: This case raises the possibil- ity of treating chronic tibial osteomyelitis caused by mixed infection with Nocardia spp and B. fragilis by applying postoperative VAC ther- apy directly to the medullary cavity and covering the residual wound with a gastrocnemius myocutaneous flap. PMID- 27377614 TI - Comparative toxicities of 3 platinum-containing chemotherapy regimens in relapsed/refractory lymphoma patients. AB - Optimal salvage chemotherapy regimen for patients with relapsed or refractory Hodgkin and non-Hodgkin lymphoma remains unclear but often based on platinum regimens. This retrospective study assesses in real life the toxicities profiles of patients with relapsed or refractory lymphoma treated with DHA (dexamethasone, high dose aracytine cytarabine) plus platinum salt (dexamethasone-High dose aracytine (cis)platin (DHAP), dexamethasone-High dose aracytine carboplatin (DHAC), or dexamethasone-High dose aracytine Oxaliplatin (DHAOX)), from February 2007 to May 2013 in 2 French hospitals. Toxicities were recorded from medical files and assessed according to the National Cancer Institute Common Toxicity Criteria version 3.0. Potential risk factors of renal insufficiency were tested by univariate analyses. A total of 276 patients were treated: 168 with DHAP (60.9%), 79 with DHAOX (28.6%), and 29 with DHAC (10.5%). Rituximab was associated in 80.1% of patients (n = 221). Renal failure was reported in 97 patients, mainly with cisplatin regimen (86.6%) leading to 8.9% grade III to IV renal failure (P = .001). Renal insufficiency was reversible in most patients but remained persistent in 24, with all of them being treated with DHAP except 1. Cisplatin-based regimen (50.0% versus 12.0%, P < .05) and female (44.6% versus 29.7%, P < .05) appeared to be at higher risks of renal failure. Platinum cumulative dose is a significant risk factor of nephrotoxicity. Hematologic toxicity was more frequent with carboplatin and cisplatin with at least 1 event (all toxicity grade) respectively in 79.3% and 71.4% of patients treated (P < .005). Auditory toxicity was mainly reported with cisplatin (n = 19; 4 grade I-II and 15 grade III-IV). Oxaliplatin was implicated in 77.6% of neurotoxicity (n = 59), mainly moderate (grade I-II). In conclusion, DHAOX and DHAC regimens have more favorable toxicity profile than DHAP regimen. Their lack of renal toxicity makes them attractive regimens, which may be interesting for patients eligible for autologous stem cell transplantation. Nevertheless, these results have to be confirmed by the therapeutic efficacy of these 3 regimens. PMID- 27377616 TI - Comparison of lidocaine/tetracaine cream and lidocaine/prilocaine cream for local anaesthesia during laser treatment of acne keloidalis nuchae and tattoo removal: results of two randomized controlled trials. AB - BACKGROUND: Pain is a common adverse effect of dermatological laser procedures. Currently, no standard topical anaesthetic cream exists for deeper dermal laser procedures. OBJECTIVES: To compare the efficacy of lidocaine/tetracaine cream and lidocaine/prilocaine cream in reducing self-reported pain during deeper dermal laser treatment of acne keloidalis nuchae (AKN) and tattoos. METHODS: We conducted two randomized, double-blind, controlled clinical trials with intrapatient, split-lesion designs: study A included patients with AKN (n = 15); study B included patients with black tattoos (n = 15). The primary end point was the patients' self-reported pain on a 10-cm visual analogue scale (VAS). Secondary objectives were the percentage of patients with adequate pain relief, willingness to pay ?25 for the cream that provided the best pain relief and safety of the creams. RESULTS: In both studies, VAS scores were lower for lidocaine/prilocaine cream, with a mean VAS difference in study A of 1.9 [95% confidence interval (CI) 1.0-2.8] and in study B of 0.6 (95% CI -0.7 to 1.9). In study A, adequate pain relief was achieved in 13% (n = 2) with lidocaine/tetracaine cream vs. 73% (n = 11) with lidocaine/prilocaine cream (P = 0.004), and in study B in 53% (n = 8) vs. 80% (n = 12), respectively (P = 0.289). In study A, 47% (n = 7) were willing to pay an additional ?25 vs. 73% (n = 11) in study B. No serious adverse events occurred. CONCLUSIONS: Lidocaine/prilocaine cream under plastic occlusion is the preferred topical anaesthetic during painful laser procedures targeting dermal chromophores. PMID- 27377615 TI - Expression and Secretion of Endostar Protein by Escherichia Coli: Optimization of Culture Conditions Using the Response Surface Methodology. AB - Endostar as a specific drug in treatment of the nonsmall cell lung cancer is produced using Escherichia coli expression system. Plackett-Burman design (PBD) and response surface methodology (RSM) are statistical tools for experimental design and optimization of biotechnological processes. This investigation aimed to predict and develop the optimal culture condition and its components for expression and secretion of endostar into the culture medium of E. coli. The synthetic endostar coding sequence was fused with PhoA signal peptide. The nine factors involved in the production of recombinant protein-postinduction temperature, cell density, rotation speed, postinduction time, concentration of glycerol, IPTG, peptone, glycine, and triton X-100-were evaluated using PBD. Four significant factors were selected based on PBD results for optimizing culture condition using RSM. Endostar was purified using cation exchange chromatography and size exclusion chromatography. The maximum level of endostar was obtained under the following condition: 13.57-h postinduction time, 0.76 % glycine, 0.7 % triton X-100, and 4.87 % glycerol. The predicted levels of endostar was significantly correlated with experimental levels (R 2 = 0.982, P = 0.00). The obtained results indicated that PBD and RSM are effective tools for optimization of culture condition and its components for endostar production in E. coli. The most important factors in the enhancement of the protein production are glycerol, glycine, and postinduction time. PMID- 27377617 TI - Couples Therapy for Intimate Partner Violence: A Systematic Review and Meta Analysis. AB - Intimate partner violence is a serious public health problem accompanied by substantial morbidity and mortality. Despite its documented impact on health, there is no widely recognized treatment of choice. Some studies indicate that couples suffering from situational violence may benefit from couples therapy, but professionals are cautious to risk the possibility of violent retaliation between partners. After a comprehensive literature search of 1,733 citations, this systematic review and meta-analysis compiles the results of six studies to investigate the effectiveness of couples therapy as a treatment for violence. Preliminary data suggest that couples therapy is a viable treatment in select situations. PMID- 27377619 TI - X-ray Absorption Spectroscopic Quantification and Speciation Modeling of Sulfate Adsorption on Ferrihydrite Surfaces. AB - Sulfate adsorption on mineral surfaces is an important environmental chemical process, but the structures and respective contribution of different adsorption complexes under various environmental conditions are unclear. By combining sulfur K-edge XANES and EXAFS spectroscopy, quantum chemical calculations, and surface complexation modeling (SCM), we have shown that sulfate forms both outer-sphere complexes and bidentate-binuclear inner-sphere complexes on ferrihydrite surfaces. The relative fractions of the complexes vary with pH, ionic strength (I), and sample hydration degree (wet versus air-dried), but their structures remained the same. The inner-sphere complex adsorption loading decreases with increasing pH while remaining unchanged with I. At both I = 0.02 and 0.1 M, the outer-sphere complex loading reaches maximum at pH ~5 and then decreases with pH, whereas it monotonically decreases with pH at I = 0.5 M. These observations result from a combination of the ionic-strength effect, the pH dependence of anion adsorption, and the competition between inner- and outer-sphere complexation. Air-drying drastically converts the outer-sphere complexes to the inner-sphere complexes. The respective contributions to the overall adsorption loading of the two complexes were directly modeled with the extended triple layer SCM by implementing the bidentate-binuclear inner-sphere complexation identified in the present study. These findings improve our understanding of sulfate adsorption and its effects on other environmental chemical processes and have important implications for generalizing the adsorption behavior of anions forming both inner- and outer-sphere complexes on mineral surfaces. PMID- 27377618 TI - Germline viral "fossils" guide in silico reconstruction of a mid-Cenozoic era marsupial adeno-associated virus. AB - Germline endogenous viral elements (EVEs) genetically preserve viral nucleotide sequences useful to the study of viral evolution, gene mutation, and the phylogenetic relationships among host organisms. Here, we describe a lineage specific, adeno-associated virus (AAV)-derived endogenous viral element (mAAV EVE1) found within the germline of numerous closely related marsupial species. Molecular screening of a marsupial DNA panel indicated that mAAV-EVE1 occurs specifically within the marsupial suborder Macropodiformes (present-day kangaroos, wallabies, and related macropodoids), to the exclusion of other Diprotodontian lineages. Orthologous mAAV-EVE1 locus sequences from sixteen macropodoid species, representing a speciation history spanning an estimated 30 million years, facilitated compilation of an inferred ancestral sequence that recapitulates the genome of an ancient marsupial AAV that circulated among Australian metatherian fauna sometime during the late Eocene to early Oligocene. In silico gene reconstruction and molecular modelling indicate remarkable conservation of viral structure over a geologic timescale. Characterisation of AAV-EVE loci among disparate species affords insight into AAV evolution and, in the case of macropodoid species, may offer an additional genetic basis for assignment of phylogenetic relationships among the Macropodoidea. From an applied perspective, the identified AAV "fossils" provide novel capsid sequences for use in translational research and clinical applications. PMID- 27377620 TI - United States National Pain Strategy for Population Research: Concepts, Definitions, and Pilot Data. AB - National Pain Strategy population research objectives include: estimating chronic pain prevalence, studying pain treatment with electronic health care data, and developing metrics to assess progress in reducing chronic pain impact. In this article, the National Pain Strategy Population Research Workgroup reviews concepts relevant to achieving these aims. High-impact chronic pain was defined as persistent pain with substantial restriction of life activities lasting 6 months or more. In pilot work, we tested a brief assessment of high-impact chronic pain, and used electronic health records data to describe pain-related health care. A mail survey of adult health plan enrollees (N = 770) reported that 14% had high-impact chronic pain. Relative to persons with lower-impact chronic pain, those with high-impact chronic pain were more often frequent users of health care for pain, reported lower quality of life, greater pain-related interference with activities, and more often reported pain at multiple anatomic locations. Analyses of health care data (N = 289,464) reported that pain patients had higher health care costs compared with others and that pain services were typically delivered in primary care. These results support the feasibility of developing data on chronic pain through national health interview surveys and large electronic health care databases. PERSPECTIVE: Pilot analyses supported the feasibility of brief chronic pain assessments suitable for national health surveys and use of electronic health care databases to develop data regarding trends in the delivery of pain treatments, costs, and effectiveness. These methods are relevant to achieving the aims of the US National Pain Strategy. PMID- 27377621 TI - Resident Macrophages in Muscle Contribute to Development of Hyperalgesia in a Mouse Model of Noninflammatory Muscle Pain. AB - Macrophages play a role in innate immunity within the body, are located in muscle tissue, and can release inflammatory cytokines that sensitize local nociceptors. In this study we investigate the role of resident macrophages in the noninflammatory muscle pain model induced by 2 pH 4.0 preservative-free sterile saline (pH 4.0) injections 5 days apart in the gastrocnemius muscle. We showed that injecting 2 pH 4.0 injections into the gastrocnemius muscle increased the number of local muscle macrophages, and depleting muscle macrophages with clodronate liposomes before acid injections attenuated the hyperalgesia produced by this model. To further examine the contribution of local macrophages to this hyperalgesia, we injected mice intramuscularly with C34, a toll-like receptor 4 (TLR4) antagonist. When given before the first pH 4.0 injection, C34 attenuated the muscle and tactile hyperalgesia produced by the model. However, when given before the second injection C34 had no effect on the development of hyperalgesia. Then to test whether activation of local macrophages sensitizes nociceptors to normally non-nociceptive stimuli we replaced either the first or second acid injection with the immune cell activator lipopolysaccharide, or the inflammatory cytokine interleukin (IL)-6. Injecting LPS or IL-6 instead of the either the first or second pH 4.0 injection resulted in a dose-dependent increase in paw withdrawal responses and decrease in muscle withdrawal thresholds. The highest doses of LPS and IL-6 resulted in development of hyperalgesia bilaterally. The present study showed that resident macrophages in muscle are key to development of chronic muscle pain. PERSPECTIVE: This article presents evidence for the role of macrophages in the development of chronic muscle pain using a mouse model. These data suggest that macrophages could be a potential therapeutic target to prevent transition of acute to chronic muscle pain particularly in tissue acidosis conditions. PMID- 27377622 TI - A catalogue of 136 microbial draft genomes from Red Sea metagenomes. AB - Earth is expected to continue warming and the Red Sea is a model environment for understanding the effects of global warming on ocean microbiomes due to its unusually high temperature, salinity and solar irradiance. However, most microbial diversity analyses of the Red Sea have been limited to cultured representatives and single marker gene analyses, hence neglecting the substantial uncultured majority. Here, we report 136 microbial genomes (completion minus contamination is >=50%) assembled from 45 metagenomes from eight stations spanning the Red Sea and taken from multiple depths between 10 to 500 m. Phylogenomic analysis showed that most of the retrieved genomes belong to seven different phyla of known marine microbes, but more than half representing currently uncultured species. The open-access data presented here is the largest number of Red Sea representative microbial genomes reported in a single study and will help facilitate future studies in understanding the physiology of these microorganisms and how they have adapted to the relatively harsh conditions of the Red Sea. PMID- 27377624 TI - Variations of rhizosphere bacterial communities in tea (Camellia sinensis L.) continuous cropping soil by high-throughput pyrosequencing approach. AB - AIMS: The goal was to investigate the dynamics of soil bacterial community in the chronosequence tea orchards. METHOD AND RESULTS: In this study, soils from tea orchards with continuously cropping histories for 1, 10 and 20 years were collected for investigating rhizosphere bacterial communities using 454 pyrosequencing. The results indicated that Gammaproteobacteria, Alphaproteobacteria, Acidobacteria and Actinobacteria were the main phyla in the tea orchard soils and accounted for more than 60% of the bacterial sequences. At the genus level, the relative abundance of beneficial bacteria, such as Pseudomonas, Rhodanobacter, Bradyrhizobium, Mycobacterium and Sphingomonas, significantly decreased in the 20-year tea orchard soils. Similar patterns of bacterial community structure were observed between 1-year and 10-year tea orchards, which significantly differed from those of 20-year tea orchards. Redundancy analysis indicated that soil organic carbon and pH showed high correlations (positive or negative) with the majority of the taxa. CONCLUSION: Long-term tea cultivation altered the composition and structure of soil bacterial community, which led to the reduction in the beneficial bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: The results can provide clues on how to regulate the soil microbial community and maintain the health of soils in tea orchard systems. PMID- 27377625 TI - Virtual drug screening for prion diseases: A valuable step? PMID- 27377623 TI - Glycolipid activators of invariant NKT cells as vaccine adjuvants. AB - Natural Killer T cells (NKT cells) are a subpopulation of T lymphocytes with unique phenotypic properties and a remarkably broad range of immune effector and regulatory functions. One subset of these cells, known as invariant NKT cells (iNKT cells), has become a significant focus in the search for new and better ways to enhance immunotherapies and vaccination. These unconventional T cells are characterized by their ability to be specifically activated by a range of foreign and self-derived glycolipid antigens presented by CD1d, an MHC class I-related antigen presenting molecule that has evolved to bind and present lipid antigens. The development of synthetic alpha-galactosylceramides as a family of powerful glycolipid agonists for iNKT cells has led to approaches for augmenting a wide variety of immune responses, including those involved in vaccination against infections and cancers. Here we review the basic background biology of iNKT cells that is relevant to their potential for improving immune responses, and summarize recent work supporting the further development of glycolipid activators of iNKT cells as a new class of vaccine adjuvants. PMID- 27377626 TI - Identification of Circulating Tumor DNA for the Early Detection of Small-cell Lung Cancer. AB - Circulating tumor DNA (ctDNA) is emerging as a key potential biomarker for post diagnosis surveillance but it may also play a crucial role in the detection of pre-clinical cancer. Small-cell lung cancer (SCLC) is an excellent candidate for early detection given there are no successful therapeutic options for late-stage disease, and it displays almost universal inactivation of TP53. We assessed the presence of TP53 mutations in the cell-free DNA (cfDNA) extracted from the plasma of 51 SCLC cases and 123 non-cancer controls. We identified mutations using a pipeline specifically designed to accurately detect variants at very low fractions. We detected TP53 mutations in the cfDNA of 49% SCLC patients and 11.4% of non-cancer controls. When stratifying the 51 initial SCLC cases by stage, TP53 mutations were detected in the cfDNA of 35.7% early-stage and 54.1% late-stage SCLC patients. The results in the controls were further replicated in 10.8% of an independent series of 102 non-cancer controls. The detection of TP53 mutations in 11% of the 225 non-cancer controls suggests that somatic mutations in cfDNA among individuals without any cancer diagnosis is a common occurrence, and poses serious challenges for the development of ctDNA screening tests. PMID- 27377627 TI - Factors associated with use of malaria control interventions by pregnant women in Buwunga subcounty, Bugiri District. AB - BACKGROUND: In Uganda, the Government has promoted the use of intermittent preventive treatment of malaria in pregnancy (IPTp) and insecticide-treated bed nets (ITNs) as malaria control strategies for pregnant women. However, their utilization among pregnant women is low. This study aimed at assessing factors associated with use of IPTp for malaria and ITNs by pregnant women in Buwunga sub county, Bugiri District. METHODS: This was a cross-sectional study, conducted in Buwunga sub-county, Bugiri District, employing quantitative data collection tools. A total of 350 household members were randomly selected to participate in the study. Data were entered and analysed using Epi info version 3.5.1; bivariable and multivariable analysis was done to assess the factors associated with use of IPTp and ITNs among pregnant women. RESULTS: The level of uptake of IPTp1 (at least one dose) was 63.7 % while IPTp2 (at least two doses) was 42.0 %. More than half (58.6 %) of the mothers had slept under an ITN the night before the survey. Slightly more than half (51.9 %) of the mothers mentioned stock outs as the major reason for not accessing IPTp and ITNs. The main factors that were statistically significant for IPTp2 uptake were the knowledge of mothers on IPTp2 (AOR 2.48 95 % CI 1.53-4.02) and providing women with free clean water at the antenatal care (ANC) clinic (AOR 3.63 95 % CI 2.06-6.39). Factors that were significant for ITN utilization included education level of mothers (AOR 2.03 95 % CI 1.09-3.78), ease of access (AOR 2.74 95 % CI 1.65-4.52), and parity (AOR 1.71 95 % CI 1.01-1.29). CONCLUSION: The level of uptake of the two recommended doses of sulfadoxine-pyrimethamine (SP) tablets for malaria prevention (IPTp2) was low, slightly more than half of the mothers slept under an ITN the night before the survey. Appropriate measures to increase the level of uptake of IPTp2 and coverage of ITNs among pregnant women should be implemented, and these include providing health education about IPTp and ITNs, and ensuring that mothers are provided with free safe clean water at ANC clinic. PMID- 27377628 TI - Risk and functional significance of psychotic experiences among individuals with depression in 44 low- and middle-income countries. AB - BACKGROUND: Studies on whether the co-occurrence of psychotic experiences (PEs) and depression confers a more pronounced decrement in health status and function compared with depression alone are scarce in the general adult population. METHOD: Data on 195 479 adults aged ?18 years from the World Health Survey were analysed. Using the World Mental Health Survey version of the Composite International Diagnostic Interview (CIDI), depression in the past 12 months was categorized into four groups: depressive episode, brief depressive episode, subsyndromal depression, and no depression. Past 12-month psychotic symptoms were assessed using four questions on positive symptoms from the CIDI. Health status across seven domains (cognition, interpersonal activities, sleep/energy, self care, mobility, pain/discomfort, vision) and interviewer-rated presence of a mental health problem were assessed. Multivariable logistic and linear regression analyses were performed to assess the associations. RESULTS: When compared with those with no depression, individuals with depression had higher odds of reporting at least one PE, and this was seen across all levels of depression severity: subsyndromal depression [odds ratio (OR) 2.38, 95% confidence interval (CI) 2.02-2.81], brief depressive episode (OR 3.84, 95% CI 3.31-4.46) and depressive episode (OR 3.75, 95% CI 3.24-4.33). Having coexisting PEs and depression was associated with a higher risk for observable illness behavior and a significant decline in health status in the cognition, interpersonal activities and sleep/energy domains, compared with those with depression alone. CONCLUSIONS: This coexistence of depression and PEs is associated with more severe social, cognitive and sleep disturbances, and more outwardly apparent illness behavior. Detecting this co-occurrence may be important for treatment planning. PMID- 27377630 TI - Cognitive deficits in single App knock-in mouse models. AB - Transgenic mouse models of Alzheimer's disease (AD) with nonphysiologic overexpression of amyloid precursor protein (APP) exhibit various unnatural symptoms/dysfunctions. To overcome this issue, mice with single humanized App knock-in (KI) carrying Swedish (NL), Beyreuther/Iberian (F), and Arctic (G) mutations in different combinations were recently developed. The validity of these mouse models of AD from a behavioral viewpoint, however, has not been extensively evaluated. Thus, using an automated behavior monitoring system, we analyzed various behavioral domains, including executive function, and learning and memory. The App-KI mice carrying NL-G-F mutations showed clear deficits in spatial memory and flexible learning, enhanced compulsive behavior, and reduced attention performance. Mice carrying NL-F mutations exhibited modest abnormalities. The NL-G-F mice had a greater and more rapid accumulation of Abeta deposits and glial responses. These findings reveal that single pathologic App-KI is sufficient to produce deficits in broad cognitive domains and that App-KI mouse lines with different levels of pathophysiology are useful models of AD. PMID- 27377631 TI - Isolated right ventricular hypoplasia caused by giant aneurysm of right coronary artery to left ventricle fistula in an adult: a case report. AB - BACKGROUND: Right ventricular hypoplasia (RVH) is often caused by tricuspid valve atresia and pulmonary valve atresia. this condition leads to low right ventricular blood volume and right ventricular maldevelopment. But, in adults, the main cause of RVH may also be associated with alloplasia of the right coronary artery, which results in an insufficient blood supply to the right ventricular myocardium. Isolated RVH caused by a right coronary artery fistula is very rare and requires immediate treatment. CASE PRESENTATION: We herein report a case involving a 45-year-old man who presented with isolated RVH caused by a giant aneurysm from the right coronary artery to a left ventricle fistula. Echocardiography showed that the right coronary artery was extremely tortuous and obviously dilated with a huge aneurysm. A fistula drained from the right coronary artery into the left ventricle. Moreover, the right heart chamber was significantly collapsed due to extrinsic compression of multiple tortuous, dilated vascular structures. The patient was referred to cardiac surgery. The giant aneurysm was resected, and the proximal and distal openings were closed directly. The fistula was also closed directly, and bypasses were constructed sequentially from the ascending aorta to three branches of the right coronary artery. CONCLUSIONS: Although standard therapeutic strategies of isolated RVH secondary to a right coronary artery fistula are not well established because of the rarity of this condition, our clinical results show that diagnostic echocardiography, coronary artery angiography, and cardiac computed tomography angiography followed by surgical treatment may be an effective management option. PMID- 27377632 TI - End-Cretaceous extinction in Antarctica linked to both Deccan volcanism and meteorite impact via climate change. AB - The cause of the end-Cretaceous (KPg) mass extinction is still debated due to difficulty separating the influences of two closely timed potential causal events: eruption of the Deccan Traps volcanic province and impact of the Chicxulub meteorite. Here we combine published extinction patterns with a new clumped isotope temperature record from a hiatus-free, expanded KPg boundary section from Seymour Island, Antarctica. We document a 7.8+/-3.3 degrees C warming synchronous with the onset of Deccan Traps volcanism and a second, smaller warming at the time of meteorite impact. Local warming may have been amplified due to simultaneous disappearance of continental or sea ice. Intra shell variability indicates a possible reduction in seasonality after Deccan eruptions began, continuing through the meteorite event. Species extinction at Seymour Island occurred in two pulses that coincide with the two observed warming events, directly linking the end-Cretaceous extinction at this site to both volcanic and meteorite events via climate change. PMID- 27377634 TI - Managed Activity Graded Exercise iN Teenagers and pre-Adolescents (MAGENTA) feasibility randomised controlled trial: study protocol. AB - INTRODUCTION: Paediatric chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a relatively common and disabling condition, yet there is a limited evidence base for treatment. There is good evidence that graded exercise therapy is moderately effective in adults with CFS/ME, but there is little evidence for the effectiveness, cost-effectiveness, acceptability or best method of delivery for paediatric CFS/ME. This study aims to investigate the acceptability and feasibility of carrying out a multicentre randomised controlled trial investigating the effectiveness of graded exercise therapy compared with activity management for children/teenagers who are mildly or moderately affected with CFS/ME. METHODS AND ANALYSIS: 100 paediatric patients (8-17 years) with CFS/ME will be recruited from 3 specialist UK National Health Service (NHS) CFS/ME services (Bath, Cambridge and Newcastle). Patients will be randomised (1:1) to receive either graded exercise therapy or activity management. Feasibility analysis will include the number of young people eligible, approached and consented to the trial; attrition rate and treatment adherence; questionnaire and accelerometer completion rates. Integrated qualitative methods will ascertain perceptions of feasibility and acceptability of recruitment, randomisation and the interventions. All adverse events will be monitored to assess the safety of the trial. ETHICS AND DISSEMINATION: The trial has received ethical approval from the National Research Ethics Service (South West-Frenchay 15/SW/0124). TRIAL REGISTRATION NUMBER: ISRCTN23962803; Pre-results. PMID- 27377636 TI - Diagnosis and mortality in prehospital emergency patients transported to hospital: a population-based and registry-based cohort study. AB - OBJECTIVE: Knowledge about patients after calling for an ambulance is limited to subgroups, such as patients with cardiac arrest, myocardial infarction, trauma and stroke, while population-based studies including all diagnoses are few. We examined the diagnostic pattern and mortality among all patients brought to hospital by ambulance after emergency calls. DESIGN: Registry-based cohort study. SETTING AND PARTICIPANTS: We included patients brought to hospital in an ambulance dispatched after emergency calls during 2007-2014 in the North Denmark Region (580 000 inhabitants). We reported hospital diagnosis according to the chapters of the International Classification of Diseases, 10th Edition (ICD-10), and studied death on days 1 and 30 after the call. Cohort characteristics and diagnoses were described, and the Kaplan-Meier method was used to estimate mortality and 95% CIs. RESULTS: In total, 148 757 patients were included, mean age 52.9 (SD 24.3) years. The most frequent ICD-10 diagnosis chapters were: 'injury and poisoning' (30.0%), and the 2 non-specific diagnosis chapters: 'symptoms and abnormal findings, not elsewhere classified' (17.5%) and 'factors influencing health status and contact with health services' (14.1%), followed by 'diseases of the circulatory system' (10.6%) and 'diseases of the respiratory system' (6.7%). The overall 1-day mortality was 1.8% (CI 1.7% to 1.8%) and 30-day mortality 4.7% (CI 4.6% to 4.8%). 'Diseases of the circulatory system' had the highest 1-day mortality of 7.7% (CI 7.3% to 8.1%) accounting for 1209 deaths. After 30 days, the highest number of deaths were among circulatory diseases (2313), respiratory diseases (1148), 'symptoms and abnormal findings, not elsewhere classified' (1119) and 'injury and poisoning' (741), and 30 days mortality in percentage was 14.7%, 11.6%, 4.3% and 1.7%, respectively. CONCLUSIONS: Patients' diagnoses from hospital stay after calling 1-1-2 in this population-based study were distributed across all ICD-10 chapters. Mortality varied widely between diagnostic groups. Non-specific diagnoses accounted for one third of the patients and contributed to mortality in terms of total number of deaths. PMID- 27377635 TI - Sleeve gastrectomy versus Roux-en-Y gastric bypass for type 2 diabetes and morbid obesity: double-blind randomised clinical trial protocol. AB - INTRODUCTION: Type 2 diabetes (T2D) in association with obesity is an increasing disease burden. Bariatric surgery is the only effective therapy for achieving remission of T2D among those with morbid obesity. It is unclear which of the two most commonly performed types of bariatric surgery, laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB), is most effective for obese patients with T2D. The primary objective of this study is to determine whether LSG or LRYGB is more effective in achieving HbA1c<6% (<42 mmol/mol) without the use of diabetes medication at 5 years. METHODS AND ANALYSIS: Single-centre, double-blind (assessor and patient), parallel, randomised clinical trial (RCT) conducted in New Zealand, targeting 106 patients. Eligibility criteria include age 20-55 years, T2D of at least 6 months duration and body mass index 35-65 kg/m(2) for at least 5 years. Randomisation 1:1 to LSG or LRYGB, used random number codes disclosed to the operating surgeon after induction of anaesthesia. A standard medication adjustment schedule will be used during postoperative metabolic assessments. Secondary outcomes include proportions achieving HbA1c<5.7% (39 mmol/mol) or HbA1c<6.5% (48 mmol/mol) without the use of diabetes medication, comparative weight loss, obesity-related comorbidity, operative complications, revision rate, mortality, quality of life, anxiety and depression scores. Exploratory outcomes include changes in satiety, gut hormone and gut microbiota to gain underlying mechanistic insights into T2D remission. ETHICS AND DISSEMINATION: Ethics approval was obtained from the New Zealand regional ethics committee (NZ93405) who also provided independent safety monitoring of the trial. Study commenced in September 2011. Recruitment completed in October 2014. Data collection is ongoing. Results will be reported in manuscripts submitted to peer-reviewed journals and in presentations at national and international meetings. TRIAL REGISTRATION NUMBERS: ACTRN12611000751976, NCT01486680; Pre-results. PMID- 27377633 TI - Early prediction of typical outcome and mild developmental delay for prioritisation of service delivery for very preterm and very low birthweight infants: a study protocol. AB - INTRODUCTION: Over 80% of very preterm (<32 weeks) and very low birthweight (<1500 g) infants will have either typical development (TD) or mild developmental delay (MDD) in multiple domains. As differentiation between TD and MDD can be difficult, infants with MDD often miss opportunities for intervention. For many clinicians, the ongoing challenge is early detection of MDD without over servicing the population. This study aims to: (1) identify early clinical biomarkers for use in this population to predict and differentiate between TD and MDD at 24 months corrected age. (2) Determine the extent to which family and caregiver factors will contribute to neurodevelopmental and behavioural outcomes. METHODS AND ANALYSIS: Participants will be a prospective cohort of 90 infants (<32 weeks and/or <1500 g). Between 34 weeks gestational age and 16 weeks post term, infants will have a series of 5 neurological, neuromotor, neurobehavioural and perceptual assessments including General Movement Assessment at preterm, writhing and fidgety age. Primary caregivers will complete questionnaires to identify social risk, maternal depression and family strain. Extensive perinatal data will be collected from the medical record. At 24 months, corrected age (c.a) infants will be assessed using standardised tools including the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley III). Longitudinal trajectories of early assessment findings will be examined to determine any predictive relationship with motor and cognitive outcomes at 24 months c.a. Published data of a cohort of Australian children assessed with the Bayley III at 24 months c.a will provide a reference group of term-born controls. ETHICS: Ethical approval has been obtained from the Queensland Children's Health Services Human Research Ethics Committee (HREC/13/QRCH/66), the University of Queensland (2013001019) and the Sunshine Coast Hospital and Health Service, SC-Research Governance (SSA/13/QNB/66). Publication of all study outcomes will be in peer reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12614000480684; Pre-results. PMID- 27377637 TI - Research funding for addressing tobacco-related disease: an analysis of UK investment between 2008 and 2012. AB - INTRODUCTION: Tobacco use is the leading cause of preventable death in the UK. However, research spending on tobacco-related disease, and particularly smoking prevention, is thought to be low. We therefore aimed to assess the relation between tobacco-related research investment and disease burden from 2008 to 2012. METHODS: We used the Health Research Classification System to classify UK government and charitable research funding by broad health category and then by tobacco prevention research and 18 WHO defined tobacco-related diseases. We used UK mortality figures to calculate disease-specific tobacco attributable deaths and then compared disease specific and tobacco prevention research investment with all cause and tobacco attributable mortality over the 5-year period and as annual averages. RESULTS: 12 922 research grants were identified with a total value of L6.69bn, an annual average of L1.34bn. Annually an average of 110 000 people die from tobacco-related disease, approximately 20% of total deaths. L130m is invested in researching tobacco-related disease each year and L5m on tobacco prevention, 10.8% and 0.42% of total annual research funding, respectively. Prevention research equated to an annual average of L46 per tobacco attributable death or one pound for every L29 spent on tobacco-related disease. Funding varied widely for diseases with different numbers of deaths (eg, lung cancer L68 per all cause death, cervical cancer L2500), similar numbers of deaths (leukaemia L983 per death, stomach cancer L43) or similar numbers of tobacco attributable deaths (eg, colorectal cancer L5k, pancreatic cancer L670, bladder cancer L340). CONCLUSIONS: Tobacco-related research funding is not related to burden of disease or level of risk. As a result certain diseases receive a disproportionately low level of research funding and disease prevention funding is even lower. PMID- 27377638 TI - Doctors' experiences and their perception of the most stressful aspects of complaints processes in the UK: an analysis of qualitative survey data. AB - OBJECTIVES: To examine doctors' experiences of complaints, including which aspects are most stressful. We also investigated how doctors felt complaints processes could be improved. DESIGN AND METHODS: A qualitative study based on a cross-sectional survey of members of the British Medical Association (BMA). We asked the following: (1) Try to summarise as best as you can your experience of the complaints process and how it made you feel. (2) What were the most stressful aspects of the complaint? (3) What would you improve in the complaints system? PARTICIPANTS: We sent the survey to 95 636 doctors, and received 10 930 (11.4%) responses. Of these, 6146 had a previous, recent or current complaint and 3417 (31.3%) of these respondents answered questions 1 and 2. We randomly selected 1000 answers for analysis, and included 100 using the saturation principle. Of this cohort, 93 responses for question 3 were available. MAIN RESULTS: Doctors frequently reported feeling powerless, emotionally distressed, and experiencing negative feelings towards both those managing complaints and the complainants themselves. Many felt unsupported, fearful of the consequences and that the complaint was unfair. The most stressful aspects were the prolonged duration and unpredictability of procedures, managerial incompetence, poor communication and perceiving that processes are biased in favour of complainants. Many reported practising defensively or considering changing career after a complaint, and few found any positive outcomes from complaints investigations. Physicians suggested procedures should be more transparent, competently managed, time limited, and that there should be an open dialogue with complainants and policies for dealing with vexatious complaints. Some felt more support for doctors was needed. CONCLUSIONS: Complaints seriously impact on doctors' psychological wellbeing, and are associated with defensive practise. This is not beneficial to patient care. To improve procedures, doctors propose they are simplified, time limited and more transparent. PMID- 27377640 TI - Correction: Study protocol for a pilot, randomised, double-blinded, placebo controlled trial of perineural local anaesthetics and steroids for chronic posttraumatic neuropathic pain in the ankle and foot: the PREPLANS study. PMID- 27377639 TI - Epidemiology of major depressive disorder in South Africa (1997-2015): a systematic review protocol. AB - INTRODUCTION: Major depressive disorder (MDD) is a leading cause of disease and disability globally and in South Africa. Epidemiological data for MDD are essential to estimate the overall disease burden in a country. The objective of the systematic review is to examine the evidence base for prevalence, incidence, remission, duration, severity, case fatality and excess mortality of MDD in South Africa from 1997 to 2015. METHODS AND ANALYSIS: We will perform electronic searches in PubMed, PsycINFO, Scopus and other bibliographical databases. Articles published between January 1997 and December 2015 will be eligible for inclusion in this review. The primary outcomes will be prevalence, incidence, remission, duration, severity, case fatality and excess mortality of MDD. The secondary outcomes will be risk factors and selected populations for MDD. If appropriate, a meta-analysis will be performed. If a meta-analysis is not possible, the review findings will be presented narratively and in tables. Subgroup analyses will be conducted with subgroups defined by population group, rural/urban settings and study designs, if sufficient data are available. ETHICS AND DISSEMINATION: The systematic review will use published data that are not linked to individuals. The review findings may have implications for future research prioritisation and disease modelling of MDD to estimate its morbidity burden in South Africa, and will be disseminated electronically and in print through peer-reviewed publications. TRIAL REGISTRATION NUMBER: International Prospective Register of Systematic Reviews (PROSPERO) CRD42015024885. PMID- 27377642 TI - Laterality of motor control as revealed in biceps electromyography: Why seizures always start in the major hemisphere. PMID- 27377641 TI - Self-Assembly of Amphiphilic Dendrimers: The Role of Generation and Alkyl Chain Length in siRNA Interaction. AB - An ideal nucleic-acid transfection system should combine the physical and chemical characteristics of cationic lipids and linear polymers to decrease cytotoxicity and uptake limitations. Previous research described new types of carriers termed amphiphilic dendrimers (ADs), which are based on polyamidoamine dendrimers (PAMAM). These ADs display the cell membrane affinity advantage of lipids and preserve the high affinity for DNA possessed by cationic dendrimers. These lipid/dendrimer hybrids consist of a low-generation, hydrophilic dendron (G2, G1, or G0) bonded to a hydrophobic tail. The G2-18C AD was reported to be an efficient siRNA vector with significant gene silencing. However, shorter tail ADs (G2-15C and G2-13C) and lower generation (G0 and G1) dendrimers failed as transfection carriers. To date, the self-assembly phenomenon of this class of amphiphilic dendrimers has not been molecularly explored using molecular simulation methods. To gain insight into these systems, the present study used coarse-grained molecular dynamics simulations to describe how ADs are able to self-assemble into an aggregate, and, specifically, how tail length and generation play a key role in this event. Finally, explanations are given for the better efficiency of G2/18-C as gene carrier in terms of binding of siRNA. This knowledge could be relevant for the design of novel, safer ADs with well optimized affinity for siRNA. PMID- 27377643 TI - 13 C dynamic nuclear polarization using isotopically enriched 4-oxo-TEMPO free radicals. AB - The nitroxide-based free radical 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) is a widely used polarizing agent in NMR signal amplification via dissolution dynamic nuclear polarization (DNP). In this study, we have thoroughly investigated the effects of 15 N and/or 2 H isotopic labeling of 4-oxo-TEMPO free radical on 13 C DNP of 3 M [1-13 C] sodium acetate samples in 1 : 1 v/v glycerol : water at 3.35 T and 1.2 K. Four variants of this free radical were used for 13 C DNP: 4-oxo-TEMPO, 4-oxo-TEMPO-15 N, 4-oxo-TEMPO-d16 and 4-oxo-TEMPO-15 N,d16 . Our results indicate that, despite the striking differences seen in the electron spin resonance (ESR) spectral features, the 13 C DNP efficiency of these 15 N and/or 2 H-enriched 4-oxo-TEMPO free radicals are relatively the same compared with 13 C DNP performance of the regular 4-oxo-TEMPO. Furthermore, when fully deuterated glassing solvents were used, the 13 C DNP signals of these samples all doubled in the same manner, and the 13 C polarization buildup was faster by a factor of 2 for all samples. The data here suggest that the hyperfine coupling contributions of these isotopically enriched 4-oxo-TEMPO free radicals have negligible effects on the 13 C DNP efficiency at 3.35 T and 1.2 K. These results are discussed in light of the spin temperature model of DNP. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27377645 TI - TAS-102, the first "cardio-gentle" fluoropyrimidine in the colorectal cancer landscape? AB - BACKGROUND: Cardiotoxicity in the form of cardiac arrhythmia, myocardial infarction, and angina-like symptoms are not rare complications of fluoropyrimidines as 5-Fluorouracil (5FU) and capecitabine. DISCUSSION: Tas-102, a novel oral fluoropyrimidine, was recently approved by FDA for the treatment of advanced and refractory colorectal cancer. Its unique mechanism of action doesn't seem linked with cardiotoxicity in clinical trials reported so far. TAS 102 may represent one of the drugs of choice for patients with advanced colorectal cancer with cardiac disease. This intriguing and clinically relevant issue is briefly examined. PMID- 27377644 TI - Luteolin reduces obesity-associated insulin resistance in mice by activating AMPKalpha1 signalling in adipose tissue macrophages. AB - AIMS/HYPOTHESIS: Inflammatory polarisation of adipose tissue macrophages (ATMs) plays a critical role in the development of obesity-associated metabolic diseases such as insulin resistance and diabetes. Our previous study indicated that dietary luteolin (LU) could prevent the establishment of insulin resistance in mice fed a high-fat diet (HFD). Here, we further investigated the effects of LU, which is a natural flavonoid, on pre-established insulin resistance and obesity associated ATM polarisation in mice. METHODS: Five-week-old C57/BL6 mice were fed on a low-fat diet or HFD for 20 weeks, with some mice receiving supplementation with 0.01% LU from weeks 1 or 10 of the HFD to assess the actions of LU on insulin resistance and ATM polarisation. Furthermore, the role of LU in metabolic dysfunction-associated macrophage phenotypes was investigated in vitro. RESULTS: Dietary LU supplementation, either for 20 weeks or from weeks 10 to 20 of an HFD, significantly improved insulin resistance in HFD-fed mice. In addition, inflammatory macrophage infiltration and polarisation were suppressed in mouse epididymal adipose tissues. Furthermore, LU treatment directly reversed lipopolysaccharide-stimulated and metabolism-regulated molecules, and induced inflammatory polarisation in mouse RAW264.7 cells and peritoneal cavity resident macrophages. Finally, using the selective AMP-activated protein kinase (AMPK) inhibitor compound C and Ampkalpha1 (also known as Prkaa1) silencing with siRNA, we found that LU activated AMPKalpha1 in macrophages to inhibit their inflammatory polarisation and enhanced insulin signals in adipocytes that were stimulated with macrophage-conditioned media. CONCLUSIONS/INTERPRETATION: Dietary LU ameliorated insulin resistance in diet-induced obese mice by promoting AMPKalpha1 signalling in ATMs. PMID- 27377646 TI - Metal Coordination Stoichiometry Controlled Formation of Linear and Hyperbranched Supramolecular Polymers. AB - Controlling the topologies of polymers is a hot topic in polymer chemistry because the physical and/or chemical properties of polymers are determined (at least partially) by their topologies. This study exploits the host-guest interactions between dibenzo-24-crown-8 and secondary ammonium salts and metal coordination interactions between 2,6-bis(benzimidazolyl)-pyridine units with metal ions (Zn(II) and/or Eu(III) ) as orthogonal non-covalent interactions to prepare supramolecular polymers. By changing the ratios of the metal ion additives (Zn(NO3 )2 and Eu(NO3 )3 ) linkers to join the host-guest dimeric complex, the linear supramolecular polymers (100 mol% Zn(NO3 )2 per ligand) and hyperbranched supramolecular polymers (97 mol% Zn(NO3 )2 and 3 mol% Eu(NO3 )3 per ligand) are separately and successfully constructed. This approach not only expands topological control over polymeric systems, but also paves the way for the functionalization of smart and adaptive materials. PMID- 27377647 TI - Off-label use of the amplatzer ductal occluder II additional size for percutaneous treatment of acute aortic occlusion in a baby. AB - We describe the case of a 5-month-old baby with a pro-coagulative condition, referred for rapid atrial tachycardia. At echocardiography we found a large free floating atrial thrombus that spontaneously embolized into the descending aorta and produced acute sub-renal occlusion. Aorta and iliac vessels were cleared using the ADO II additional sizes device. (c) 2016 Wiley Periodicals, Inc. PMID- 27377648 TI - Comparing large covariance matrices under weak conditions on the dependence structure and its application to gene clustering. AB - Comparing large covariance matrices has important applications in modern genomics, where scientists are often interested in understanding whether relationships (e.g., dependencies or co-regulations) among a large number of genes vary between different biological states. We propose a computationally fast procedure for testing the equality of two large covariance matrices when the dimensions of the covariance matrices are much larger than the sample sizes. A distinguishing feature of the new procedure is that it imposes no structural assumptions on the unknown covariance matrices. Hence, the test is robust with respect to various complex dependence structures that frequently arise in genomics. We prove that the proposed procedure is asymptotically valid under weak moment conditions. As an interesting application, we derive a new gene clustering algorithm which shares the same nice property of avoiding restrictive structural assumptions for high-dimensional genomics data. Using an asthma gene expression dataset, we illustrate how the new test helps compare the covariance matrices of the genes across different gene sets/pathways between the disease group and the control group, and how the gene clustering algorithm provides new insights on the way gene clustering patterns differ between the two groups. The proposed methods have been implemented in an R-package HDtest and are available on CRAN. PMID- 27377649 TI - Nationwide population-based cohort study of psychiatric disorders in individuals with Ehlers-Danlos syndrome or hypermobility syndrome and their siblings. AB - BACKGROUND: To assess the risk of psychiatric disorders in Ehlers-Danlos syndrome (EDS) and hypermobility syndrome. METHODS: Nationwide population-based matched cohort study. EDS, hypermobility syndrome and psychiatric disorders were identified through Swedish national registries. Individuals with EDS (n = 1,771) were matched with comparison individuals (n = 17,710). Further, siblings to individuals with EDS who did not have an EDS diagnosis themselves were compared with matched comparison siblings. Using conditional logistic regression, risk of autism spectrum disorder (ASD), bipolar disorder, attention deficit hyperactivity disorder (ADHD), depression, attempted suicide, suicide and schizophrenia were estimated. The same analyses were conducted in individuals with hypermobility syndrome (n = 10,019) and their siblings. RESULTS: EDS was associated with ASD: risk ratio (RR) 7.4, 95 % confidence interval (95 % CI) 5.2-10.7; bipolar disorder: RR 2.7, CI 1.5-4.7; ADHD: RR 5.6, CI 4.2-7.4; depression: RR 3.4, 95 % CI 2.9-4.1; and attempted suicide: RR 2.1, 95 % CI 1.7-2.7, but not with suicide or schizophrenia. EDS siblings were at increased risk of ADHD: RR 2.1, 95 % CI 1.4-3.3; depression: RR 1.5, 95 % CI 1.1-1.8; and suicide attempt: RR 1.8, 95 % CI 1.4-2.3. Similar results were observed for individuals with hypermobility syndrome and their siblings. CONCLUSIONS: Individuals with EDS and hypermobility syndrome are at increased risks of being diagnosed with psychiatric disorders. These risk increases may have a genetic and/or early environmental background as suggested by evidence showing that siblings to patients have elevated risks of certain psychiatric disorders. PMID- 27377650 TI - Nucleotide-binding oligomerization domain-containing protein 2 prompts potent inflammatory stimuli during Neospora caninum infection. AB - Neospora caninum is an apicomplexan parasite responsible for major economic losses due to abortions in cattle. Innate immune responses are crucial for host resistance against the infection, however the molecules involved in parasite recognition are still poorly understood. Nod2 is a cytosolic receptor that recognizes several pathogens and its role during N. caninum infection has not yet been described. In that sense, we evaluated the role of Nod2 in host response against this parasite. We found that infection of macrophages induced increased expression of Nod2, which colocalized with the parasites' vacuoles. Nod2 deficient macrophages showed an impaired induction of pro-inflammatory cytokines, increased production of modulatory molecules, and failure to restrict parasite replication. In vivo, Nod2-knockout mice showed a reduction of MAPK phosphorylation and proinflammatory cytokines, followed by decreased inflammation in target organs and increment in parasite burden. Surprisingly, these mice were partially resistant to lethal doses of tachyzoites. In addition, these phenomena were not observed in Rip2-/- mice. In conclusion, our study indicates that Nod2 dependent responses account for N. caninum elimination. On the other hand, the inflammatory milieu induced by this innate receptor provoked pathogenesis and death in severe experimental neosporosis. PMID- 27377651 TI - Comparing the performance of the public, social security and private health subsystems in Argentina by core dimensions of primary health care. AB - BACKGROUND: Most Latin American health systems are comprised of public (PubS), social security (SSS) and private (PrS) subsystems. These subsystems coexist, causing health care fragmentation and population segmentation. OBJECTIVE: To estimate the extent of subsystem cross-coverage in a geographically bounded population (Rosario city) and to compare the subsystems' performance on primary health care (PHC) dimensions. METHODS: Through a cross-sectional, interviewer administered survey to a representative sample (n = 822) of the Rosario population, we measured the percentage of cross-coverage (people with usual source of care in one subsystem but also covered by another subsystem) and the health services' performance by core PHC dimensions, as reported by each subsystem's usual users. We compared the subsystems' performance using chi-square analysis and one-way analysis of variance testing. We analyzed whether the observed differences were coherent with the predominant institutional and organizational features of each subsystem. RESULTS: Overall, 39.3% of the population was affiliated with the PubS, 44.8% with the SSS and 15.9% with the PrS. Cross-coverage was reported by 40.6% of respondents. The performance of the PubS was weak on accessibility but strong on person-and-community-oriented care, the opposite of the PrS. The SSS combined the strengths of the other two subsystems. CONCLUSION: Rosario's health system has a high percentage of cross coverage, contributing to issues of fragmentation, segmentation, financial inequity and inefficiency. The overall performance of the SSS was better than that of the PrS and PubS, though each subsystem had a particular performance pattern with areas of strength and weakness that were consistent with their institutional and organizational profiles. PMID- 27377652 TI - The Cell Ontology 2016: enhanced content, modularization, and ontology interoperability. AB - BACKGROUND: The Cell Ontology (CL) is an OBO Foundry candidate ontology covering the domain of canonical, natural biological cell types. Since its inception in 2005, the CL has undergone multiple rounds of revision and expansion, most notably in its representation of hematopoietic cells. For in vivo cells, the CL focuses on vertebrates but provides general classes that can be used for other metazoans, which can be subtyped in species-specific ontologies. CONSTRUCTION AND CONTENT: Recent work on the CL has focused on extending the representation of various cell types, and developing new modules in the CL itself, and in related ontologies in coordination with the CL. For example, the Kidney and Urinary Pathway Ontology was used as a template to populate the CL with additional cell types. In addition, subtypes of the class 'cell in vitro' have received improved definitions and labels to provide for modularity with the representation of cells in the Cell Line Ontology and Reagent Ontology. Recent changes in the ontology development methodology for CL include a switch from OBO to OWL for the primary encoding of the ontology, and an increasing reliance on logical definitions for improved reasoning. UTILITY AND DISCUSSION: The CL is now mandated as a metadata standard for large functional genomics and transcriptomics projects, and is used extensively for annotation, querying, and analyses of cell type specific data in sequencing consortia such as FANTOM5 and ENCODE, as well as for the NIAID ImmPort database and the Cell Image Library. The CL is also a vital component used in the modular construction of other biomedical ontologies-for example, the Gene Ontology and the cross-species anatomy ontology, Uberon, use CL to support the consistent representation of cell types across different levels of anatomical granularity, such as tissues and organs. CONCLUSIONS: The ongoing improvements to the CL make it a valuable resource to both the OBO Foundry community and the wider scientific community, and we continue to experience increased interest in the CL both among developers and within the user community. PMID- 27377654 TI - Pembrolizumab: first experience with recurrent primary central nervous system (CNS) tumors. AB - Patients with progressive primary brain tumors (PBT) are attracted to promising new treatments, even prior to convincing data. Anti-PD1 immunotherapies have been in the spotlight since publication of groundbreaking results for metastatic melanoma with pembrolizumab (PBL). Our objective was to report on the response and toxicity of PBL in patients with advanced PBT. We retrospectively reviewed the charts of 22 patients (17 adults and 5 children) with recurrent central nervous system tumors treated with PBL. We analyzed prior antineoplastic therapies, steroid usage, and outcomes. Patients received a median of two neoplastic therapies prior to PBL, and a median of three infusions of PBL in adults and four in children. Twelve patients (9 adults and 3 children) started PBL on steroids (median dose in adults 4 mg; range 2-8, and in children 1.5 mg, range 0.5-4) and five patients received steroids later during PBL treatment. Twelve patients (10 adults and 2 children) received concomitant bevacizumab with PBL. Side effects were minimal. All patients showed progressive tumor growth during therapy. Median OS from the start of PBL was 2.6 months in adults and 3.2 months in children. Two GB patients underwent tumor resection following treatment with PBL. Tumor-lymphocytic response in these cases was unremarkable, and PD-L1 immuno-staining was negative. In this series of 22 patients with recurrent primary brain tumors, PBL showed no clinical or histologic efficacy. We do not recommend further use of PBL for recurrent PBT unless convincing prospective clinical trial data are published. PMID- 27377653 TI - Does the choice of antiepileptic drug affect survival in glioblastoma patients? AB - Patients with glioblastoma (GBM) often suffer from symptomatic epilepsy. Older antiepileptic drugs (AEDs) which affect the enzyme system cytochrome P450 have been in extensive use, but there is an increasing focus on interactions with other drugs. This study investigated whether newer AEDs with little or no enzyme effect are increasingly preferred. Previous research has indicated that valproate improves survival in GBM. We investigated the impact of AEDs on overall survival in GBM patients. All GBM patients diagnosed in Norway 2004-2010 were included through a linkage of national registries, and follow-up data on the malignancy and drug usage were analyzed. In a multivariate cox proportional-hazards regression, AEDs were adjusted for each other and for relevant factors. Immortal time bias was eliminated with time-dependent variables. The study population was 1263 patients with histologically confirmed GBM. Carbamazepine was the most frequently prescribed AED to patients diagnosed with GBM during 2004-2006, while levetiracetam was increasingly prescribed to patients diagnosed later. Taking AEDs on a reimbursement code of epilepsy was not beneficial for survival. None of the six AEDs valproate, levetiracetam, carbamazepine, oxcarbazepine, lamotrigine or phenytoin significantly altered overall survival. There has been a shift in the prescriptions of AEDs to GBM patients from older to newer AEDs over time. We found no significant survival benefit in GBM patients neither from treatment with AEDs for epilepsy in general, nor from the usage of six separate AEDs. PMID- 27377656 TI - Alzheimer's disease: A review of its visual system neuropathology. Optical coherence tomography-a potential role as a study tool in vivo. AB - Alzheimer's disease (AD) is a prevalent, long-term progressive degenerative disorder with great social impact. It is currently thought that, in addition to neurodegeneration, vascular changes also play a role in the pathophysiology of the disease. Visual symptoms are frequent and are an early clinical manifestation; a number of psychophysiologic changes occur in visual function, including visual field defects, abnormal contrast sensitivity, abnormalities in color vision, depth perception deficits, and motion detection abnormalities. These visual changes were initially believed to be solely due to neurodegeneration in the posterior visual pathway. However, evidence from pathology studies in both animal models of AD and humans has demonstrated that neurodegeneration also takes place in the anterior visual pathway, with involvement of the retinal ganglion cells' (RGCs) dendrites, somata, and axons in the optic nerve. These studies additionally showed that patients with AD have changes in retinal and choroidal microvasculature. Pathology findings have been corroborated in in-vivo assessment of the retina and optic nerve head (ONH), as well as the retinal and choroidal vasculature. Optical coherence tomography (OCT) in particular has shown great utility in the assessment of these changes, and it may become a useful tool for early detection and monitoring disease progression in AD. The authors make a review of the current understanding of retinal and choroidal pathological changes in patients with AD, with particular focus on in vivo evidence of retinal and choroidal neurodegenerative and microvascular changes using OCT technology. PMID- 27377655 TI - A Large Outbreak of Fulminant Bacterial Endophthalmitis after Intravitreal Injection of Counterfeit Bevacizumab. AB - PURPOSE: This study reports the findings in a large series of patients with acute bacterial endophthalmitis after intravitreal injection of bevacizumab (IVB) in two eye hospitals. METHODS: Medical records were reviewed for patients who presented with acute fulminant endophthalmitis in one or two eyes following intravitreal injection of bevacizumab from two separate batches in two eye hospitals. RESULTS: Twenty-eight eyes of 21 patients presented with acute endophthalmitis 12-48 hours after IVB injection. Cultures from the eyes and the vials were positive for E. coli and Citrobacter, each in one of the hospitals. All patients were initially treated with topical, intravitreal, and systemic antibiotics. Twenty-four eyes underwent pars plana vitrectomy. Best corrected visual acuity (BCVA) was 1.27 +/- 0.89 logMAR before IVB injecti,on which decreased to 2.80 +/- 0.45 LogMAR after presentation of endophthalmitis and 2.12 +/- 0.97 logMAR three months after IVB injection. Final visual acuity was found to be no light perception in four eyes. CONCLUSIONS: This large outbreak of E.coli and Citrobacter endophthalmitis occurred after intravitreal injection of counterfeit bevacizumab. Visual outcomes were very poor. PMID- 27377657 TI - Plasma E-selectin levels can play a role in the development of diabetic retinopathy. AB - PURPOSE: Diabetic retinopathy is one of the leading causes of blindness. There are several risk factors, such as the duration of diabetes or glycemic control of the patient; however, several biochemical factors also alter the process. Our aim was to investigate the role of soluble E-selectin in the formation of diabetic retinopathy. PATIENTS AND METHODS: Fifty-seven patients (37 female and 20 male, aged 61.71 +/- 12.31 years) and 14 healthy control subjects (ten female and four male, aged 63.06 +/- 10.46 years) were enrolled in the study. We measured the soluble E-selectin level in the plasma of patients by ELISA. All patients underwent careful ophthalmological examination, including ophthalmoscopy and color fundus photography, while diabetic retinopathy grading was performed in line with the 2012 classification of the American Academy of Ophthalmology (AAO). RESULTS: The soluble E-selectin level was significantly higher in patients with diabetes compared to controls (32.95 ng/ml vs. 26.55 ng/ml, p = 0.03). Dividing patients into groups by the presence of retinopathy, the E-selectin level was also significantly higher in the retinopathy group (p < 0.05). When we examined diabetic patients by the severity of retinopathy (groups A, B, and C, by the guidelines of the AAO), however, we did not find any significant difference in soluble E-selectin levels, although it tended to be higher in group B. CONCLUSIONS: An elevated E-selectin level can play a role in the development of diabetic retinopathy, but it does not seem to alter disease severity. However, glycemic control and the reduction of cardiovascular risk factors may also alter the level of E-selectin that might play a role in the prevention of diabetic retinopathy. PMID- 27377658 TI - Accuracy and reproducibility of the ETDRS visual acuity chart: methodological issues. PMID- 27377660 TI - Editorial. PMID- 27377659 TI - Protection against death and renal failure by renin-angiotensin system blockers in patients with diabetes and kidney disease. AB - INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are widely used to block the renin-angiotensin system (RAS). Yet it remains uncertain whether these drugs are equally effective and safe. METHODS: Systematic reviews and meta-analyses of ACEis/ARBs in diabetes and kidney disease published in PubMed, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases were searched for clinical outcomes including all cause mortality, end-stage renal disease (ESRD), hyperkalemia and cough. RESULTS: Eight meta-analyses included 2177-61,264 patients with follow-up of 6-108 months. RAS blockers reduced mortality (relative risk ratio (RR), 0.90, 95% confidence interval (CI), 0.86-0.95) without heterogeneity. The death protection was significant specifically with ACEis (RR, 0.85, 95% CI, 0.79-0.91), but not with ARBs. Protection against ESRD was homogenously evident by ARBs (RR, 0.79, 95% CI, 0.73-0.87), ACEis (RR, 0.79, 95% , 0.64-0.94), and both (RR, 0.79, 95% CI, 0.73 0.87). Significant side effects were hyperkalemia by ARBs (RR, 2.44, 95% CI, 1.13 5.26), and cough by ACEis (RR, 2.38, 95% CI, 1.75-3.22) CONCLUSIONS: In patients with diabetes and kidney disease, ACEis and ARBs are consistently protective for the development of ESRD. Use of ACEis alone additionally reduces deaths and increases the risk for cough. Use of ARBs alone increases the risk for hyperkalemia without additional benefit of death protection. PMID- 27377661 TI - Sparse Bayesian Learning for Obtaining Sparsity of EEG Frequency Bands Based Feature Vectors in Motor Imagery Classification. AB - Effective common spatial pattern (CSP) feature extraction for motor imagery (MI) electroencephalogram (EEG) recordings usually depends on the filter band selection to a large extent. Subband optimization has been suggested to enhance classification accuracy of MI. Accordingly, this study introduces a new method that implements sparse Bayesian learning of frequency bands (named SBLFB) from EEG for MI classification. CSP features are extracted on a set of signals that are generated by a filter bank with multiple overlapping subbands from raw EEG data. Sparse Bayesian learning is then exploited to implement selection of significant features with a linear discriminant criterion for classification. The effectiveness of SBLFB is demonstrated on the BCI Competition IV IIb dataset, in comparison with several other competing methods. Experimental results indicate that the SBLFB method is promising for development of an effective classifier to improve MI classification. PMID- 27377662 TI - Which Brain Regions are Important for Seizure Dynamics in Epileptic Networks? Influence of Link Identification and EEG Recording Montage on Node Centralities. AB - Nodes in large-scale epileptic networks that are crucial for seizure facilitation and termination can be regarded as potential targets for individualized focal therapies. Graph-theoretical approaches based on centrality concepts can help to identify such important nodes, however, they may be influenced by the way networks are derived from empirical data. Here we investigate evolving functional epileptic brain networks during 82 focal seizures with different anatomical onset locations that we derive from multichannel intracranial electroencephalographic recordings from 51 patients. We demonstrate how the various methodological steps (from the recording montage via node and link inference to the assessment of node centralities) affect importance estimation and discuss their impact on the interpretability of findings in the context of pathophysiological aspects of seizure dynamics. PMID- 27377663 TI - Asynchronous Detection of Trials Onset from Raw EEG Signals. AB - Clinical processing of event-related potentials (ERPs) requires a precise synchrony between the stimulation and the acquisition units that are guaranteed by means of a physical link between them. This precise synchrony is needed since temporal misalignments during trial averaging can lead to high deviations of peak times, thus causing error in diagnosis or inefficiency in classification in brain computer interfaces (BCIs). Out of the laboratory, mobile EEG systems and BCI headsets are not provided with the physical link, thus being inadequate for acquisition of ERPs. In this study, we propose a method for the asynchronous detection of trials onset from raw EEG without physical links. We validate it with a BCI application based on the dichotic listening task. The user goal was to attend the cued auditory message and to report three keywords contained in it while ignoring the other message. The BCI goal was to detect the attended message from the analysis of auditory ERPs. The rate of successful onset detection in both synchronous (using the real onset) and asynchronous (blind detection of trial onset from raw EEG) was 73% with a synchronization error of less than 1[Formula: see text]ms. The level of synchronization provided by this proposal would allow home-based acquisition of ERPs with low cost BCI headsets and any media player unit without physical links between them. PMID- 27377664 TI - Hydroxyapatite nanoparticle injectable hydrogel scaffold to support osteogenic differentiation of human mesenchymal stem cells. AB - Bone loss associated with degenerative disease and trauma is a clinical problem increasing with the aging population. Thus, effective bone augmentation strategies are required; however, many have the disadvantages that they require invasive surgery and often the addition of expensive growth factors to induce osteoblast differentiation. Here, we investigated a LaponiteO crosslinked, pNIPAM DMAc copolymer (L-pNIPAM-co-DMAc) hydrogel with hydroxyapatite nanoparticles (HAPna), which can be maintained as a liquid ex vivo, injected via narrow-gauge needle into affected bone, followed by in situ gelation to deliver and induce osteogenic differentiation of human mesenchymal stem cells (hMSC). L-pNIPAM-co DMAc hydrogels were synthesised and HAPna added post polymerisation. Commercial hMSCs from one donor (Lonza) were incorporated in liquid hydrogel, the mixture solidified and cultured for up to 6 weeks. Viability of hMSCs was maintained within hydrogel constructs containing 0.5 mg/mL HAPna. SEM analysis demonstrated matrix deposition in cellular hydrogels which were absent in acellular controls. A significant increase in storage modulus (G') was observed in cellular hydrogels with 0.5 mg/mL HAPna. Semi-quantitative immunohistochemistry and histological analysis demonstrated that bone differentiation markers and collagen deposition was induced within 48 h, with increased calcium deposition with time. The thermally triggered hydrogel system, described here, was sufficient without the need of additional growth factors or osteogenic media to induce osteogenic differentiation of commercial hMSCs. Preliminary data presented here will be expanded on multiple patient samples to ensure differentiation is seen in these samples. This system could potentially reduce treatment costs and simplify the treatment strategy for orthopaedic repair and regeneration. PMID- 27377665 TI - Xenotransplantation of pig chondrocytes: therapeutic potential and barriers for cartilage repair. AB - Transplantation may be the best option for the repair of many cartilage lesions including early osteoarthritis. Currently, autologous and allogeneic chondrocytes are grafted into cartilage defects to treat selected patients with moderate clinical success. However, their limited use justifies exploring novel therapies for cartilage repair. Xenotransplantation could become a solution by offering high cell availability, quality and genetic engineering capabilities. The rejection process of xenogeneic cartilage is thus being elucidated in order to develop counteractive strategies. Initial studies determined that pig cartilage xenografts are rejected by a slow process comprising humoral and cellular responses in which the galactose alpha1,3-galactose antigen participates. Since then, our group has identified key mechanisms of the human response to pig chondrocytes (PCs). In particular, human antibody and complement contribute to PC rejection by inducing a pro-inflammatory milieu. Furthermore, PCs express and up regulate molecules which are functionally relevant for a variety of cellular immune responses (SLA-I, the potent co-stimulatory molecule CD86, and adhesion molecules VCAM-1 and ICAM-1). These participate by triggering a T cell response, as well as supporting a prominent role of the innate immune responses led by natural killer (NK) cells and monocytes/macrophages. Human NK cells lyse PCs by using selected NK activating receptors, whereas human monocytes are activated by PCs to secrete cytokines and chemokines. All this knowledge sets the bases for the development of genetic engineering approaches designed to avert rejection of xenogeneic chondrocytes and leads the way to developing new clinical applications for cartilage repair. PMID- 27377666 TI - Pericellular colocalisation and interactive properties of type VI collagen and perlecan in the intervertebral disc. AB - The aim of this study was to immunolocalise type VI collagen and perlecan and determine their interactive properties in the intervertebral disc (IVD). Confocal laser scanning microscopy co-localised perlecan with type VI collagen as pericellular components of IVD cells and translamellar cross-bridges in ovine and murine IVDs. These cross-bridges were significantly less abundant in the heparin sulphate deficient Hspg2 exon 3 null mouse IVD than in wild type. This association of type VI collagen with elastic components provides clues as to its roles in conveying elastic recoil properties to annular tissues. Perlecan and type VI collagen were highly interactive in plasmon resonance studies. Pericellular colocalisation of perlecan and type VI collagen provides matrix stabilisation and cell-matrix communication which allows IVD cells to perceive and respond to perturbations in their biomechanical microenvironment. Perlecan, at the cell surface, provides an adhesive interface between the cell and its surrounding extracellular matrix. Elastic microfibrillar structures regulate tensional connective tissue development and function. The 2010 Global Burden of Disease study examined 291 disorders and identified disc degeneration and associated low back pain as the leading global musculoskeletal disorder emphasising its massive socioeconomic impact and the need for more effective treatment strategies. A greater understanding of how the IVD achieves its unique biomechanical functional properties is of great importance in the development of such therapeutic measures. PMID- 27377667 TI - Palladium-Catalyzed Asymmetric Arylation of Trifluoromethylated/Perfluoroalkylated 2-Quinazolinones with High Enantioselectivity. AB - Asymmetric arylation of 4-fluoroalkyl-2-quinazolinone derivatives with arylboronic acids proceeded smoothly in the presence of a cationic palladium catalyst (1 mol %) coordinated with a chiral phosphinooxazoline (phox) ligand to create the corresponding fluorine-containing arylated dihydroquinazolinones in high yields and with greater than 99 % ee. PMID- 27377669 TI - Resuscitative endovascular balloon occlusion of the aorta (REBOA) in the pre hospital setting: An additional resuscitation option for uncontrolled catastrophic haemorrhage. AB - This report describes the first use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in the pre-hospital setting to control catastrophic haemorrhage. The patient, who had fallen 15 meters, suffered catastrophic internal haemorrhage associated with a pelvic fracture. He was treated by London's Air Ambulance's Physician-Paramedic team. This included insertion of a REBOA balloon catheter at the scene to control likely fatal exsanguination. The patient survived transfer to hospital, emergency angio embolization and subsequent surgery. He was discharged neurologically normal after 52 days and went on to make a full recovery. The poor prognosis in catastrophic torso haemorrhage and novel endovascular methods of haemorrhage control are discussed. Also the challenges of Pre-Hospital REBOA are discussed together with the training and governance required for a safe system. PMID- 27377668 TI - Isolation of protein complexes from the model legume Medicago truncatula by tandem affinity purification in hairy root cultures. AB - Tandem affinity purification coupled to mass spectrometry (TAP-MS) is one of the most powerful techniques to isolate protein complexes and elucidate protein interaction networks. Here, we describe the development of a TAP-MS strategy for the model legume Medicago truncatula, which is widely studied for its ability to produce valuable natural products and to engage in endosymbiotic interactions. As biological material, transgenic hairy roots, generated through Agrobacterium rhizogenes-mediated transformation of M. truncatula seedlings, were used. As proof of concept, proteins involved in the cell cycle, transcript processing and jasmonate signalling were chosen as bait proteins, resulting in a list of putative interactors, many of which confirm the interologue concept of protein interactions, and which can contribute to biological information about the functioning of these bait proteins in planta. Subsequently, binary protein protein interactions among baits and preys, and among preys were confirmed by a systematic yeast two-hybrid screen. Together, by establishing a M. truncatula TAP MS platform, we extended the molecular toolbox of this model species. PMID- 27377670 TI - Echocardiographic left ventricular systolic dysfunction early after resuscitation from cardiac arrest does not predict mortality or vasopressor requirements. AB - BACKGROUND/AIMS: Echocardiographic abnormalities are common after resuscitation from cardiac arrest. The association between echocardiographic findings with vasopressor requirements and mortality are not well described. We sought to determine the associations between echocardiographic abnormalities and mortality, vasopressor requirements and organ failure after cardiac arrest. METHODS: We prospectively evaluated 55 adult subjects undergoing transthoracic echocardiography within 24h after resuscitation from cardiac arrest. We evaluated the association between 2D echocardiographic and Doppler measurements and mortality, Sequential Organ Failure Assessment (SOFA) scores and vasopressor requirements. RESULTS: Inpatient mortality was 60%. Mean left ventricular ejection fraction (LVEF) was 43.6%; LVEF was <40% in 36% of subjects. None of the measured echocardiographic parameters (including LVEF) was significantly associated with inpatient mortality (all p>0.1). Subjects with LVEF <40% more often had shockable arrest rhythms and patients resuscitated from shockable rhythms had lower mean LVEF (36.2% vs. 52.3%, p=0.001). There was no correlation between markers of right and left ventricular systolic or diastolic function (including LVEF and Doppler parameters) with vasopressor requirements, lactate levels or SOFA scores. CONCLUSION: Echocardiographic parameters (including LVEF) were not associated with inpatient mortality after cardiac arrest. Vasopressor requirements and organ failure severity were not associated with multiple echocardiographic markers of systolic function. PMID- 27377671 TI - Synthesis and Biological Evaluation of Iodoglucoazomycin (I-GAZ), an Azomycin Glucose Adduct with Putative Applications in Diagnostic Imaging and Radiotherapy of Hypoxic Tumors. AB - Iodoglucoazomycin (I-GAZ; N-(2-iodo-3-(6-O-glucosyl)propyl)-2-nitroimidazole), a non-glycosidic nitroimidazole-6-O-glucose adduct, was synthesized, radioiodinated, and evaluated as a substrate of glucose transporter 1 (GLUT1) for radiotheranostic (therapy+diagnostic) management of hypoxic tumors. Nucleophilic iodination of the nosylate synthon of I-GAZ followed by deprotection afforded I GAZ in 74 % overall yield. I-GAZ was radioiodinated via 'exchange' labeling using [(123/131) I]iodide (50-70 % RCY) and then purified by Sep-PakTM (>96 % RCP). [(131) I]I-GAZ was stable in 2 % ethanolic solution in sterile water for 14 days when stored at 5 degrees C. In cell culture, I-GAZ was found to be nontoxic to EMT-6 cells at concentrations <0.5 mm, and weakly radiosensitizing (SER 1.1 at 10 % survival of EMT-6 cells; 1.2 at 0.1 % survival in MCF-7 cells). The hypoxic/normoxic uptake ratio of [(123) I]I-GAZ in EMT-6 cells was 1.46 at 2 h, and under normoxic conditions the uptake of [(123) I]I-GAZ by EMT-6 cells was unaltered in the presence of 5 mm glucose. The biodistribution of [(131) I]I-GAZ in EMT-6 tumor-bearing Balb/c mice demonstrated rapid clearance from blood and extensive renal and hepatic excretion. Tumor/blood and tumor/muscle ratios reached ~3 and 8, respectively, at 4 h post-injection. Regression analysis of the first order polynomial plots of the blood and tumor radioactivity concentrations supported a perfusion-excretion model with low hypoxia-dependent binding. [(131) I]I-GAZ was found to be stable in vivo, and did not deiodinate. PMID- 27377672 TI - TRPC3-mediated Ca(2+) entry contributes to mouse airway smooth muscle cell proliferation induced by lipopolysaccharide. AB - Airway remodeling is a histopathological hallmark of chronic respiratory diseases that includes airway smooth muscle cell (ASMC) proliferation. Canonical transient receptor potential channel-3 (TRPC3)-encoded nonselective cation channels (NSCCs) are important native constitutively active channels that play significant roles in physiological and pathological conditions in ASMCs. Lipopolysaccharides (LPSs), known as lipoglycans and endotoxin, have been proven to be inducers of airway remodeling, though the mechanisms remain unclear. We hypothesized that TRPC3 is important in LPS-induced airway remodeling by regulating ASMC proliferation. To test this hypothesis, mouse ASMCs were cultured with or without LPS for 48h. Cell viability, TRPC3 protein expression, NSCC currents and changes in intracellular calcium concentration ([Ca(2+)]i) were then analyzed using an MTT assay, western blotting, whole-cell patch clamp and calcium imaging, respectively. The results showed that LPS treatment significantly induced ASMC proliferation, up-regulation of TRPC3 protein expression and enhancement of NSCC currents, resting [Ca(2+)]i and ACh-elicited changes in [Ca(2+)]i. TRPC3 blocker Gd(3+), TRPC3 blocking antibody or TRPC3 gene silencing by siRNA significantly inhibited LPS-induced up-regulation of TRPC3 protein, enhancement of NSCC currents, resting [Ca(2+)]i and ACh-elicited changes in [Ca(2+)]i, eventually inhibiting LPS-induced ASMCproliferation. These results demonstrated that TRPC3 mediated Ca(2+) entry contributed to LPS-induced ASMC proliferation and identified TRPC3 as a possible key target in airway remodeling intervention. PMID- 27377673 TI - Redox Reducible and Hydrolytically Degradable PEG-PLA Elastomers as Biomaterial for Temporary Drug-Eluting Medical Devices. AB - With the aim to develop biomaterials for temporary medical devices, a series of novel reducible and/or degradable elastomers has been prepared from PLA-b-PEG-b PLA copolymers photo-crosslinked with diallyl sulfide or pentaerythritol tetrakis(3-mercaptopropionate). Thermal and mechanical properties, including elastic limit and Young modulus, are assessed. Degradation is then evaluated under standard hydrolytic conditions. Reducibility of a selected elastomer is then illustrated using 2-mercaptoethanol or glutathione as reducing agents. The redox-sensitivity of the selected elastomer and the possibility to modulate the degradability are shown. Considering drug-eluting elastomeric devices applications, anti-inflammatory drug ibuprofen loading is illustrated with the two simplest elastomer formulations. A rapid or slow linear release is observed as a function of the low or high molecular weight of the triblock pre-polymers. Finally, the cytocompatibility of the degradable elastomers is assessed with regard to their potential to favor or inhibit L929 murine fibroblasts proliferation as a function of the hydrophilicity/hydrophobicity of the triblock copolymers. PMID- 27377674 TI - Underdiagnosing of Mycoplasma pneumoniae infections as revealed by use of a respiratory multiplex PCR panel. AB - We compared a multiplex PCR diagnostic approach against specific PCR diagnosis for detection of Mycoplasma pneumoniae infection. Seventy-five percent of all M. pneumoniae infections were only detected "unintentionally" by the use of the multiplex PCR indicating underdiagnosing of M. pneumoniae due to absence of clinical suspicion. PMID- 27377675 TI - The potential of molecular diagnostics and serum procalcitonin levels to change the antibiotic management of community-acquired pneumonia. AB - Two diagnostic bundles were compared in 127 evaluable patients admitted with community-acquired pneumonia (CAP). Diagnostic modalities in all patients included cultures of sputum (if obtainable) and blood, urine for detection of the antigens of Streptococcus pneumoniae and Legionella pneumophila, and nasal swabs for PCR probes for S. pneumoniae and Staphylococcus aureus. At least one procalcitonin level was measured in all patients. For virus detection, patients were randomized to either a 5-virus, lab-generated PCR panel or the broader and faster FilmArray PCR panel. Overall, an etiologic diagnosis was established in 71% of the patients. A respiratory virus was detected in 39%. The potential for improved antibiotic stewardship was evident in 25 patients with only detectable respiratory virus and normal levels of PCT. PMID- 27377677 TI - An electronic interface to routinize outcomes assessment and streamline clinic workflow. PMID- 27377678 TI - Trimethylamine-N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: A randomized controlled trial. AB - SCOPE: Trimethylamine-N-oxide (TMAO), a metabolite linked to the gut microbiota, is associated with excess risk of heart disease. We hypothesized that (i) TMAO response to animal source foods would vary among healthy men and (ii) this response would be modified by their gut microbiome. METHODS AND RESULTS: A crossover feeding trial in healthy young men (n = 40) was conducted with meals containing TMAO (fish), its dietary precursors, choline (eggs) and carnitine (beef), and a fruit control. Fish yielded higher circulating and urinary concentrations of TMAO (46-62 times; p < 0.0001), trimethylamine (8-14 times; p < 0.0001), and dimethylamine (4-6-times; P<0.0001) than eggs, beef, or the fruit control. Circulating TMAO concentrations were increased within 15 min of fish consumption, suggesting that dietary TMAO can be absorbed without processing by gut microbes. Analysis of 16S rRNA genes indicated that high-TMAO producers (>=20% increase in urinary TMAO in response to eggs and beef) had more Firmicutes than Bacteroidetes (p = 0.04) and less gut microbiota diversity (p = 0.03). CONCLUSION: Consumption of fish yielded substantially greater increases in circulating TMAO than eggs or beef. The higher Firmicutes to Bacteroidetes enrichment among men exhibiting a greater response to dietary TMAO precursor intake indicates that TMAO production is a function of individual differences in the gut microbiome. PMID- 27377679 TI - Rural residence, farming environment, and allergic diseases in Argentinean adolescents. AB - RATIONALE: Little is known about residence in a rural or farming environment and allergic diseases in Latin America. METHODS: Cross-sectional study of rural residence and current wheeze, current asthma and current symptoms of allergic rhino-conjunctivitis in 1,804 adolescents (ages 13-14 years) attending 31 schools in urban and rural areas of San Francisco (Cordoba, Argentina). Rural residence was classified as never, previous, and current. Duration of rural residence was categorized as 0, >0 but <=5 years, and >5 years. Current wheeze, current asthma, and current allergic rhino-conjunctivitis were defined on the basis of responses to an extensively validated questionnaire from the International Study of Asthma and Allergies in Childhood. Logistic regression was used for the multivariable analysis of rural residence and the outcomes of interest. RESULTS: After adjustment for current smoking and other covariates, current rural residence (odds ratio [OR] = 0.15, 95% confidence interval [CI] = 0.03-0.81) and rural residence for >5 years (OR = 0.32, 95%CI = 0.12-0.84) were significantly associated with reduced odds of current wheeze. In a multivariable analysis, current residence in a rural area (OR = 0.52, 95%CI = 0.32-0.86) and rural residence for >5 years (OR = 0.44, 95%CI = 0.26-0.73) were significantly associated with reduced odds of allergic rhino-conjunctivitis. This association was no longer significant after additional adjustment for current residence in a dairy farm, which was significantly associated with reduced odds of allergic rhino-conjunctivitis. Similarly, current regular contact with farm animals was significantly associated with reduced odds of allergic rhino-conjunctivitis. CONCLUSIONS: Among Argentinean adolescents, current rural residence and rural residence for >5 years were associated with reduced odds of current wheeze and allergic rhino-conjunctivitis. These potential protective effects may be explained by a dairy farm environment, including regular contact with farm animals. Pediatr Pulmonol. 2017;52:21-28. (c) 2016 Wiley Periodicals, Inc. PMID- 27377680 TI - The Metalloprotease Neprilysin Degrades and Inactivates Apelin Peptides. AB - The apelinergic system is a mammalian peptide hormone network with key physiological roles. Apelin isoforms and analogues are believed to be promising therapeutics for cardiovascular disease. Despite extensive studies on apelin-13 degradation patterns, only one protease, angiotensin-converting enzyme 2 (ACE2), had been implicated in its physiological regulation. Through use of a peptide based fluorescent probe, we identified the metalloprotease neprilysin (NEP, a target for Entresto used in treatment of heart failure) as an enzyme that cleaves apelin isoforms. In vitro NEP proteolysis generated fragments that lacked the ability to bind to the apelin receptor, thereby making NEP the first protease to fully inactivate apelin. The involvement of NEP in the apelinergic system contributes to the understanding of its role in cardiovascular physiology. PMID- 27377681 TI - Temporomandibular joint involvement in patients with multiple myeloma-a retrospective study. AB - Multiple myeloma (MM) is a common hematological malignancy that has widespread manifestations in multiple organs, including bones and joints. This retrospective study aimed to evaluate the involvement of the temporomandibular joint (TMJ) in patients with MM. Consecutive subjects with a diagnosis of MM who presented to the oral and maxillofacial surgery clinic for routine evaluation between 2008 and 2014 were identified. Patients who had a computed tomography (CT) scan of the TMJs as part of their MM staging were included in the study. Outcome variables were the presence of TMJ myelomatous changes on CT and the presence of TMJ symptoms. Of the 88 patients included in the study, 28 demonstrated TMJ myelomatous lesions on CT scans and 10 patients complained of TMJ pain or dysfunction. The CT scans of seven of the 10 symptomatic patients demonstrated myelomatous involvement of the TMJ area. Myelomatous involvement of the TMJ is common in MM patients and the majority of lesions are asymptomatic. An MM patient complaining of temporomandibular symptoms is relatively highly likely to having a lesion in the TMJ. Diagnosing the myelomatous lesions in the TMJ is important for accurate hemato-oncologic staging and providing treatment without delay. PMID- 27377682 TI - A study of the prevalence of dyslipidemia among the adult population of Ahvaz, Iran. AB - BACKGROUND: Hypercholesterolemia is one of the main causes of the disease burden in developed and developing countries. The present study is planned to access the prevalence of dyslipidemia and its risk factors among the general population of Ahvaz over 20 years of age. METHOD: In this descriptive-analytic study, using multi-stage cluster method, out of the 25 existing health centers in the city of Ahvaz (four health centers in the Eastern Ahvaz and two centers in the west were chosen based on the population they covered). The blood samples of the participants were taken after 12h of fasting for measure FBS, TG, Chol, HDLand LDL level their heights, and weights were measured using the standard methods. Interviewing the participants, the research questionnaires were filled by the trained health workers. RESULTS: Out of 2505 participants, 1155 samples (%46.1) were male with mean age of 42.9+/-14.5years and 1350 samples (%53.9) were women with the mean age of 39.9+/-12.6 years. The prevalence of dyslipidemia among the individuals over 20 years of age in Ahvaz was %80.9 (%75.9 in male and %85.1 in female). Age and BMI were positively correlated with increase in the risk of dyslipidemia. Women had a higher risk of dyslipidemia CONCLUSION: This study showed that more than %80 over 20 years old Ahvazian population had dyslipidemia(female more than male). Age and BMI are positively correlated with increasing dyslipidemia in my population. PMID- 27377683 TI - Metabolic syndrome and C reactive protein in patients undergoing angiography: Inevitable association? AB - BACKGROUND: The Metabolic Syndrome (MS) is characterized by a set of risk factors, which causes metabolic and inflammatory changes that increase vascular risk and may promote the development of atherosclerosis. Changes in lifestyle are related to obesity and associated diseases such as hypertension, type 2 diabetes mellitus, MS and cardiovascular disease (CVD). AIMS: This study aimed to evaluate the relationship of MS components and high sensitivity C Reactive Protein (hsCRP) in patients undergoing arteriography. METHODS: A group of patients undergoing arteriography was recruited in order we could evaluate the metabolic profile, levels of hsCRP and number of obstructions in the arteries. RESULTS: Most of our patients underwent arteriography are more likely to have hypertension, glucose intolerance, dyslipidemia, and central obesity, thus, MS is prevalent in this group. They also tend to exhibit higher values of hsCRP, lower values for the estimative of the size of the LDL-c particle and higher number of obstruction in the arteries. CONCLUSION: We may say that the improvement of the above parameters could reduce inflammation and oxidative stress and vascular damages what would extend life expectancy and quality of life of this group of patients. PMID- 27377684 TI - Association of glutathione-S-transferase with patients of type 2 diabetes mellitus with and without nephropathy. AB - STATEMENTS OF THE PROBLEM: Hyperglycemia induced oxidative stress is implicated as a contributor to the onset and progression of type 2 diabetes mellitus (T2DM) and its complications like diabetic nephropathy (DN). Glutathione-S-transferase (GST) is primarily involved in the neutralization of reactive oxygen species (ROS) by enzymatic conjugation with the scavenger peptide glutathione (GSH). Therefore, present study was aimed to evaluate the role of GST along with oxidative stress markers and their correlation in patients with Type 2 diabetes mellitus with and without nephropathy. METHODS: This study comprised of 300 participants divided into three groups of 100 each: healthy controls (HC), T2DM without complications and DN. Plasma GST, malondialdehyde (MDA), reduced GSH levels and ferric reducing ability of plasma (FRAP) were estimated spectrophotometrically. RESULTS: Highest GST levels was observed in T2DM which was significantly higher (p<0.05) as compared to DN and HC. However, GSH and FRAP levels were found to be significantly lowest whereas MDA levels were significantly highest in DN as compared to T2DM and HC. GST showed a significant negative correlation with GSH, FRAP and positive correlation with MDA in both patients groups. CONCLUSIONS: Highest activity of GST in T2DM might be as a compensatory mechanism in response to oxidative stress. GST is found to have significant negative association with decreased GSH. Altered redox milieu in DN collectively conspire to increase the risk of renal damage in T2DM. PMID- 27377685 TI - Predictors of sleep disorders among patients with type 2 diabetes mellitus. AB - AIMS: This study examined the prevalence of sleep disorders (SD) and self reported sleep symptoms and risk factors among adult patients diagnosed with T2DM. METHODS: Data were obtained from the 2012 US National Health and Wellness Survey, an annual Internet-based survey. A total of 7239 participants reported a diagnosis of T2DM. Patients also provided information on diagnosis of SD (e.g., insomnia, sleep breathing disorder, other sleep conditions, etc.) and regularly experienced sleep symptoms (e.g., difficulty falling asleep, sleep apnea, daytime sleepiness, difficulty staying awake, etc.). Logistic regressions were used to examine factors associated with SD and symptoms. RESULTS: The average age was 59.9 (standard deviation=12.2), 59.5% were male, 24.4% were diagnosed with SD, 76.8% reported experiencing any sleep symptom regularly (difficulty falling asleep, 30.5%; sleep apnea, 17.4%; daytime sleepiness, 26.8%; difficulty staying awake, 10.1%). Logistic regression models showed the strongest predictors of diagnosed SD were obesity class (OC) III (OR=2.20), White (OR=1.92), OC II (OR=1.57), smoking (OR=1.57), lower income (OR=1.49-1.19), unemployment (OR=1.38), and comorbidities (OR=1.35), all p<0.05. The strongest predictors of any sleep symptom were OC III (OR=2.22), OC II (OR=1.78), lower income (OR=1.74 1.24), female gender (OR=1.72), OC I (OR=1.60), White (OR=1.54), and smoking (OR=1.47), all p<0.05. CONCLUSIONS: Almost 25% of patients with T2DM were diagnosed with SD and over 75% reported experiencing at least one sleep symptom regularly. SD and symptoms were strongly associated with obesity, White ethnicity, gender, low income, and smoking. Interventions focusing on weight management and smoking cessation have shown to improve T2DM and may improve SD. PMID- 27377686 TI - Medical cost of type 2 diabetes attributable to physical inactivity in the United States in 2012. AB - AIMS: Type 2 diabetes has grown to epidemic proportions in the U.S. and physical activity levels in the population continues to remain low, although it is one of the primary preventive strategies for diabetes. The objectives of this study were to estimate the direct medical costs of type 2 diabetes attributable to not meeting physical activity Guidelines and to physical inactivity in the U.S. in 2012. METHODS: This was a cross sectional study that used physical activity prevalence data from the Behavioral Risk Factor Surveillance System to estimate the population attributable risk percentage for type 2 diabetes. These data were combined with the prevalence and cost data of type 2 diabetes to estimate the cost of type 2 diabetes attributable to not meeting physical activity Guidelines and to inactivity in 2012. RESULTS: The cost of type 2 diabetes in the U.S. in 2012, attributable to not meeting physical activity guidelines was estimated to be $18.3 billion, and that attributable to physical inactivity was estimated to be $4.65 billion. Based on sensitivity analyses, these estimates ranged from $10.19 billion to $27.43 billion for not meeting physical activity guidelines and $2.59 billion-$6.98 billion for physical inactivity in the year 2012. CONCLUSIONS: This study shows that billions of dollars could be saved annually just in terms of type 2 diabetes cost in the U.S., if the entire adult population met physical activity guidelines. Physical activity promotion, particularly at the environmental and policy level should be a priority in the population. PMID- 27377687 TI - Understanding Diabetic Foot Infection and its Management. AB - Diabetic Foot Ulcers (DFUs), a dreadful micro-vascular complication is liable for substantial increase in morbidity and mortality. DFU is a complicated amalgam of neuropathy, peripheral arterial diseases, foot deformities and infection. Spanning the spectrum from superficial cellulitis, microbial flora leads to chronic ostemyelitis and gangrenous extremity lower limb amputations. Wounds without affirmation of soft tissue or bone infection do not require antibiotic therapy. Treatment of mild and moderate infection requires empiric therapy covering gram-positive cocci, whereas severe or infection caused by drug resistant organisms needs broad spectrum anti-microbial targeting aggressive gram negative aerobes and obligate anaerobes. Definitive therapy employed should be based on culture reports and clinical response. Evaluation of bone infection requires imaging by plain radiographs or MRI to increase sensitivity and specificity. Surgical interventions are must and may range from minor debridement to resections or revascularization and major amputations depending upon wound severity. On time and forceful management of diabetic foot ulcers by employing multidisciplinary management approaches focusing on prevention, learning, regular foot assessment, aggressive intervention, and optimal use of therapeutic footwear can often prevent exacerbation of the difficulty and eliminate the potential for amputation. Here, we review recent studies addressing diabetic foot infections with emphasis on pathophysiology, exclusive risk factors; evaluation including physical inspection, laboratory investigations, relevant treatment strategies and assessment of infection severity. PMID- 27377689 TI - Cardiovascular medication adherence among patients with cardiac disease: a systematic review. AB - AIMS: The aim of this study was to critically appraise and synthesize the best available evidence on the effectiveness of interventions suitable for delivery by nurses, designed to enhance cardiac patients' adherence to their prescribed medications. BACKGROUND: Cardiac medications have statistically significant health benefits for patients with heart disease, but patients' adherence to prescribed medications remains suboptimal. DESIGN: A systematic quantitative review of intervention effects. DATA SOURCES: We conducted systematic searches for English-language, peer-reviewed randomized controlled trial publications via Medline, EMBASE, CINAHL, the Cochrane Library, ProQuest, Web of Science and Google Scholar published between January 2004-December 2014. REVIEW METHODS: According to pre-determined inclusion and exclusion criteria, eligible studies were identified and data extracted using a predefined form. Of 1962 identified papers; 14 studies met the study inclusion criteria, were assessed for risk of bias using the Cochrane Collaboration tool; and included in the review. RESULTS: Study findings were presented descriptively; due to the heterogeneity of studies meta-analysis was not possible. Included papers described interventions categorized as: (1) multifaceted; and (2) behavioural and educational, comprising: (a) text message and mail message; (b) telephone calls; (c) motivational interviewing and (d) nurse-led counselling and education. CONCLUSIONS: Substantial heterogeneity limited the robustness of conclusions, but this review indicated that motivational interviewing, education and phone or text messaging appeared promising as means to enhance cardiac medication adherence. Future research should integrate multifaceted interventions that target individual behaviour change to enhance adherence to cardiovascular medications, to build on the beneficial outcomes indicated by this review. PMID- 27377688 TI - An association of serum vistafin level and number of circulating endothelial progenitor cells in type 2 diabetes mellitus patients. AB - BACKGROUND: The decreased number and impaired functions of endothelial progenitor cells (EPCs) may associate with cardiovascular disease (CV) including atherosclerosis. However, the role of vistafin in regulation of angiogenic EPC subset maturation in T2DM patients without known atherosclerosis is still not fully understood. THE AIM OF THE STUDY: To investigate an association of serum vistafin level and number of circulating EPCs in T2DM patients beyond known CV disease. METHODS: This case-control observational investigation was evolved 54 subjects with T2DM and 35 healthy volunteers. The flow cytometry was used for predictably distinguishing cell subsets, which depend on expression of CD45, CD34, CD14, Tie-2, and VEGFR2. Biomarkers were measured at baseline of the study. RESULTS: All T2DM patients were divided depending median of vistafin level (5.88ng/mL) in to two cohorts with low vistafin level (<5.88ng/mL; n=29) and high vistafin level (>=5.88ng/mL; n=25) respectively. Logistic regression analysis has shown that visfatin, hs-CRP, age and BMI were the best variables in the prediction of EPC number labeled as CD14+CD309+ and CD14+CD309+Tie2+ cells. After adjustment of the model to age and BMI elevated visfatin level remained the best predictor for both CD14+CD309+ and CD14+CD309+Tie2+ EPCs (OR 0.92, 95% CI: 0.88 0.95; P=0.001 and OR 0.90, 95% CI: 0.87-0.96; P=0.001 respectively). CONCLUSION: We found that elevated level of vistafin was an independent predictor for declined numerous of non-classical EPCs labeled as CD14+CD309+ and CD14+CD309+Tie2+, whereas CD34+ subsets of EPCs did not associate with vistafin level in T2DM individuals. PMID- 27377690 TI - Type 2 diabetes is associated with a higher incidence of hospitalization for pulmonary embolism in Spain: Analysis of hospital discharge data during 2004 2013. AB - BACKGROUND AND OBJECTIVE: We compared the incidence and outcome of pulmonary embolism (PE) in individuals with and without type 2 diabetes mellitus (T2DM) in Spain during 2004-2013. METHODS: The study was based on National Hospital Discharge Data, and the study population comprised patients hospitalized for PE. Annual incidence rates were classified according to T2DM status. In-hospital mortality (IHM), length of hospital stay (LOHS), comorbidities and use of diagnosis and therapeutic procedures were analysed. RESULTS: We identified 123 872 discharges of patients (56 361 men and 67 511 women) with PE as their primary diagnosis (15.3% with T2DM). Incidence of discharge diagnoses of PE increased significantly in all groups. Crude rates were higher in diabetic patients. A positive association was identified between T2DM and PE: adjusted IRR was 2.00 (95% CI: 1.95-2.05) for men and 2.50 (95% CI: 2.45-2.57) for women. LOHS, readmissions and IHM decreased significantly for both groups. An association between IHM and risk factors (older age, Charlson comorbidity index >3, atrial fibrillation and cancer) was observed. T2DM was associated with higher IHM in men (OR: 1.22, 95% CI: 1.12-1.32) and women (OR: 1.24, 95% CI: 1.15-1.33). The use of computed tomography pulmonary angiography increased significantly overtime. CONCLUSION: We confirmed that in both men and women, diabetes was an independent risk factor for IHM. The incidence of discharge of patients with PE increased significantly during the study period. Diabetic men and women had a higher risk of hospitalization for PE than non-diabetic men and women. Diabetic women had higher IHM than diabetic men. PMID- 27377693 TI - Mitochondrial dysfunction in bipolar disorder: Evidence, pathophysiology and translational implications. AB - Bipolar disorder (BD) is a chronic psychiatric illness characterized by severe and biphasic changes in mood. Several pathophysiological mechanisms have been hypothesized to underpin the neurobiology of BD, including the presence of mitochondrial dysfunction. A confluence of evidence points to an underlying dysfunction of mitochondria, including decreases in mitochondrial respiration, high-energy phosphates and pH; changes in mitochondrial morphology; increases in mitochondrial DNA polymorphisms; and downregulation of nuclear mRNA molecules and proteins involved in mitochondrial respiration. Mitochondria play a pivotal role in neuronal cell survival or death as regulators of both energy metabolism and cell survival and death pathways. Thus, in this review, we discuss the genetic and physiological components of mitochondria and the evidence for mitochondrial abnormalities in BD. The final part of this review discusses mitochondria as a potential target of therapeutic interventions in BD. PMID- 27377691 TI - Neurobiological signatures associated with alcohol and drug use in the human adolescent brain. AB - Magnetic resonance (MR) techniques provide opportunities to non-invasively characterize neurobiological milestones of adolescent brain development. Juxtaposed to the critical finalization of brain development is initiation of alcohol and substance use, and increased frequency and quantity of use, patterns that can lead to abuse and addiction. This review provides a comprehensive overview of existing MR studies of adolescent alcohol and drug users. The most common alterations reported across substance used and MR modalities are in the frontal lobe (63% of published studies). This is not surprising, given that this is the last region to reach neurobiological adulthood. Comparatively, evidence is less consistent regarding alterations in regions that mature earlier (e.g., amygdala, hippocampus), however newer techniques now permit investigations beyond regional approaches that are uncovering network-level vulnerabilities. Regardless of whether neurobiological signatures exist prior to the initiation of use, this body of work provides important direction for ongoing prospective investigations of adolescent brain development, and the significant impact of alcohol and substance use on the brain during the second decade of life. PMID- 27377694 TI - Commentary: Are Children Like Werewolves? Full Moon and Its Association with Sleep and Activity Behaviors in an International Sample of Children. PMID- 27377692 TI - Aging and the HPA axis: Stress and resilience in older adults. AB - Hypothalamic-pituitary-adrenal (HPA) axis function may change over the course of aging, and altered diurnal or stress-induced secretion of the hormone cortisol could predispose older adults to negative health outcomes. We propose that psychological resilience may interact with diurnal cortisol to affect health outcomes later in life. Emotion regulation and social support are two constructs that contribute to resilience and exhibit age-specific patterns in older adults. Determining how the use of resilience resources interacts with age-related diurnal cortisol will improve our understanding of the pathways between stress, resilience, and well-being. In this review, we assess published studies evaluating diurnal cortisol in older adults to better understand differences in their HPA axis functioning. Evidence thus far suggests that diurnal cortisol may increase with age, although cross-sectional studies limit the conclusions that can be drawn. We also review extant evidence connecting age-specific signatures of emotion regulation and social support with diurnal cortisol. Conclusions are used to propose a preliminary model demonstrating how resilience resources may modulate the effects of cortisol on health in aging. PMID- 27377695 TI - Effects of Imiquimod on Hair Follicle Stem Cells and Hair Cycle Progression. AB - Topical imiquimod (IMQ) application is widely used as a model for psoriasiform like skin inflammation in mice. Although the effects on the epidermis are well characterized, it is unclear how IMQ affects hair follicles and cycling. Here we investigated how IMQ affects hair follicle stem cells and whether the timing of IMQ application influences the immune infiltrate. Our results show that IMQ application at mid and late telogen activated hair follicle stem cells leading to premature hair cycle entry (anagen), which was accompanied by massive infiltration of inflammatory macrophages and gamma delta T cells, whereas the number of the respective resident populations decreased. Interestingly, high resident macrophage numbers were present in Rag2-/- mice and were maintained after IMQ treatment explaining why IMQ-induced anagen was reduced. This could be rescued after macrophage depletion suggesting that resident macrophages inhibit whereas inflammatory infiltrating macrophages stimulate hair follicle stem cell activation. The expression of the anagen-inhibiting factor BMP-4 was reduced by IMQ treatment as well as the activating factors Wnt showing that IMQ-induced hair follicle stem cell activation occurs by a Wnt-independent mechanism involving inflammatory cytokines such as CCL2 and TNF-alpha. On the basis of our findings, we recommend conducting experiments with IMQ during mid and late telogen as the biggest differences in immune cell composition are observed. PMID- 27377696 TI - Different Propionibacterium acnes Phylotypes Induce Distinct Immune Responses and Express Unique Surface and Secreted Proteomes. AB - Propionibacterium acnes is a skin commensal bacterium that contributes to the development of acne vulgaris and other infections. Recent work revealed that P. acnes clinical isolates can be classified into distinct phylotypes, several of which have associations with healthy skin or acne. We sought to determine if these phylotypes induce different immunological responses and express protein factors that may contribute to their disease associations. We found that acne associated P. acnes phylotypes induced 2- to 3-fold higher levels of IFN-gamma and IL-17 in peripheral blood mononuclear cells compared with healthy phylotypes. On the other hand, P. acnes phylotypes associated with healthy skin induced 2- to 4-fold higher levels of IL-10. Comparative proteomic analysis of P. acnes phylotypes revealed a differential expression of several proteins, including an adhesion protein that was expressed at least 10-fold higher in acne-associated phylotypes and a cell surface hydrolase expressed in all phylotypes except those associated with healthy skin. Taken together, our data provide insight into how specific P. acnes phylotypes influence immune responses and the pathogenesis of acne. PMID- 27377697 TI - Inactivation of RUNX3/p46 Promotes Cutaneous T-Cell Lymphoma. AB - The key role of RUNX3 in physiological T-cell differentiation has been extensively documented. However, information on its relevance for the development of human T-cell lymphomas or leukemias is scarce. Here, we show that alterations of RUNX3 by either heterozygous deletion or methylation of its distal promoter can be observed in the tumor cells of 15 of 21 (71%) patients suffering from Sezary syndrome, an aggressive variant of cutaneous T-cell lymphoma. As a consequence, mRNA levels of RUNX3/p46, the isoform controlled by the distal promoter, are significantly lower in Sezary syndrome tumor cells. Re-expression of RUNX3/p46 reduces cell viability and promotes apoptosis in a RUNX3/p46low cell line of cutaneous T-cell lymphoma. Based on this, we present evidence that RUNX3 can act as a tumor suppressor in a human T-cell malignancy and suggest that this effect is predominantly mediated through transcripts from its distal promoter, in particular RUNX3/p46. PMID- 27377698 TI - The Cutaneous Microbiome and Aspects of Skin Antimicrobial Defense System Resist Acute Treatment with Topical Skin Cleansers. AB - The human skin microbiome has been suggested to play an essential role in maintaining health by contributing to innate defense of the skin. These observations have inspired speculation that the use of common skin washing techniques may be detrimental to the epidermal antibacterial defense system by altering the microbiome. In this study, several common skin cleansers were used to wash human forearms and the short-term effect on the abundance of the antimicrobial peptide LL-37 and the abundance and diversity of bacterial DNA was measured. Despite small but significant decreases in the amount of LL-37 on the skin surface shortly after washing, no significant change in the bacterial community was detected. Furthermore, Group A Streptococcus did not survive better on the skin after washing. In contrast, the addition of antimicrobial compounds such as benzalkonium chloride or triclocarban to soap before washing decreased the growth of Group A Streptococcus applied after rinse. These results support prior studies that hand washing techniques in the health care setting are beneficial and should be continued. Additional research is necessary to better understand the effects of chronic washing and the potential impact of skin care products on the development of dysbiosis in some individuals. PMID- 27377699 TI - Molecular Profiling of Immune Activation Associated with Regression of Melanoma Metastases Induced by Diphencyprone. PMID- 27377700 TI - Discrimination of Dysplastic Nevi from Common Melanocytic Nevi by Cellular and Molecular Criteria. AB - Dysplastic nevi (DNs), also known as Clark's nevi or atypical moles, are distinguished from common melanocytic nevi by variegation in pigmentation and clinical appearance, as well as differences in tissue patterning. However, cellular and molecular differences between DNs and common melanocytic nevi are not completely understood. Using cDNA microarray, quantitative RT-PCR, and immunohistochemistry, we molecularly characterized DNs and analyzed the difference between DNs and common melanocytic nevi. A total of 111 probesets (91 annotated genes, fold change > 2.0 and false discovery rate < 0.25) were differentially expressed between the two lesions. An unexpected finding in DNs was altered differentiation and activation of epidermal keratinocytes with increased expression of hair follicle-related molecules (keratin 25, trichohyalin, ribonuclease, RNase A family, 7) and inflammation-related molecules (S100A7, S100A8) at both genomic and protein levels. The immune microenvironment of DNs was characterized by an increase of T helper type 1 (IFNgamma) and T helper type 2 (IL13) cytokines as well as an upregulation of oncostatin M and CXCL1. DUSP3, which regulates cellular senescence, was identified as one of the disease discriminative genes between DNs and common melanocytic nevi by three independent statistical approaches and its altered expression was confirmed by immunohistochemistry. The molecular and cellular changes in which the epidermal melanin unit undergoes follicular differentiation as well as upregulation of defined cytokines could drive complex immune, epidermal, and pigmentary alterations. PMID- 27377702 TI - Professor Jean-Pierre Lambilliotte (1933-2011). PMID- 27377701 TI - Smyd5 plays pivotal roles in both primitive and definitive hematopoiesis during zebrafish embryogenesis. AB - Methylation of histone tails plays a pivotal role in the regulation of a wide range of biological processes. SET and MYND domain-containing protein (SMYD) is a methyltransferase, five family members of which have been identified in humans. SMYD1, SMYD2, SMYD3, and SMYD4 have been found to play critical roles in carcinogenesis and/or the development of heart and skeletal muscle. However, the physiological functions of SMYD5 remain unknown. To investigate the function of Smyd5 in vivo, zebrafish were utilised as a model system. We first examined smyd5 expression patterns in developing zebrafish embryos. Smyd5 transcripts were abundantly expressed at early developmental stages and then gradually decreased. Smyd5 was expressed in all adult tissues examined. Loss-of-function analysis of Smyd5 was then performed in zebrafish embryos using smyd5 morpholino oligonucleotide (MO). Embryos injected with smyd5-MO showed normal gross morphological development, including of heart and skeletal muscle. However, increased expression of both primitive and definitive hematopoietic markers, including pu.1, mpx, l-plastin, and cmyb, were observed. These phenotypes of smyd5-MO zebrafish embryos were also observed when we introduced mutations in smyd5 gene with the CRISPR/Cas9 system. As the expression of myeloid markers was elevated in smyd5 loss-of-function zebrafish, we propose that Smyd5 plays critical roles in hematopoiesis. PMID- 27377703 TI - Prostaglandin E2 stimulates urokinase-type plasminogen activator receptor via EP2 receptor-dependent signaling pathways in human AGS gastric cancer cells. AB - Aberrant expression of urokinase-type plasminogen activator receptor (uPAR) has been observed in human gastric cancers. Prostaglandin E2 (PGE2 ), whose biosynthesis is catalyzed by cyclooxygenase-2 (COX-2), is implicated in cancer metastasis; however, the cellular and molecular mechanisms of PGE2 -driven uPAR expression are yet to be elucidated in human gastric cancer AGS cells. In this study, we showed that PGE2 induces uPAR expression in concentration- and time dependent manners. Furthermore, using antagonists and siRNA, we found that among the four subtypes of PGE2 receptors, EP2 receptors are involved in PGE2 -induced uPAR expression. PGE2 induced the activation of Src, epidermal growth factor receptor (EGFR), c-Jun NH2 -terminal kinase (JNK), extracellular signal-regulated kinase (Erk), and p38 mitogen activated protein kinase (p38 MAPK). Specific inhibitor and mutagenesis studies showed that Src, EGFR, JNK1/2, and Erk1/2 are involved in PGE2 -induced uPAR expression. PGE2 induces EP2-dependent phosphorylation of Src, while the activation of Src-dependent EGFR leads to the phosphorylation of JNK1/2 and Erk1/2. Deletion and site-directed mutagenesis studies demonstrated the involvement of transcription factor activator protein (AP)-1 and nuclear factor-kappa B (NF-kappaB) in PGE2 -induced uPAR expression. EGFR-dependent MAPKs (JNK1/2 and Erk1/2) function as the upstream signaling molecules in the activation of AP-1 and NF-kappaB, respectively. AGS cells pre treated with PGE2 showed remarkably enhanced invasiveness, which was partially abrogated by uPAR-neutralizing antibodies. To the best of our knowledge, this is the first report that PGE2 -induced uPAR expression, which stimulates invasiveness of human gastric cancer AGS cells, is mediated by the EP2 receptor dependent Src/EGFR/JNK1/2, Erk1/2/AP-1, and Src/EGFR/JNK1/2, Erk1/2/NF-kappaB cascades. (c) 2016 Wiley Periodicals, Inc. PMID- 27377704 TI - Partial recovery of senescence and differentiation disturbances in CD8+ T cell effector-memory cells in HIV-1 infection after initiation of anti-retroviral treatment. AB - Immune senescence as well as disturbed CD8+ T cell differentiation are a hallmark of chronic HIV infection. Here, we investigated to what extent immune senescence is reversible after initiation of anti-retroviral treatment (ART). Peripheral blood mononuclear cells (PBMCs) from a cohort of HIV patients with different disease courses, including untreated viral controllers (n = 10), viral non controllers (n = 16) and patients on ART (n = 20), were analysed and compared to uninfected controls (n = 25) by flow cytometry on bulk and HIV-specific major histocompatibility complex (MHC) class I tetramer+ CD8+ T cells for expression of the memory markers CCR7 and CD45RO, as well as the senescence marker CD57 and the differentiation and survival marker CD127. Furthermore, a subset of patients was analysed longitudinally before and after initiation of ART. Frequencies of CD57+ CD8+ T cells decreased after initiation of ART in central memory (Tcm) but not in effector memory T cell populations (TemRO and TemRA). The frequency of CD127+ CD8+ cells increased in Tcm and TemRO. We observed a reduction of CD127- T cells in Tcm, TemRO and partially in TemRA subsets after initiation of ART. Importantly, HIV-specific CD8+ TemRO cells predominantly displayed a CD127- CD57+ phenotype in untreated HIV-patients, whereas the CD127+ CD57- phenotype was under represented in these patients. The frequency of the CD127+ CD57- CD8+ T cell subpopulation correlated strongly with absolute CD4+ counts in HIV-infected patients before and after initiation of ART. These findings can be interpreted as a phenotypical correlate of CD8+ memory T cell differentiation and the premature 'ageing' of the immune system, which was even observed in successfully virally suppressed HIV patients. PMID- 27377705 TI - Patterns of expressed emotion in adolescent eating disorders. AB - BACKGROUND: This goal of this study was to understand the patterns of expressed emotions (EEs) in adolescent eating disorders. As such, this study compared EE among families of adolescents with anorexia nervosa (AN), bulimia nervosa (BN), and a psychiatric control group, major depressive disorder (MDD). This study also examined the influence of family status (intact vs. nonintact) and the presence of siblings on EE. METHODS: Two-hundred and fifteen adolescents (ages 12-19) and their families were recruited for this study including 121 adolescents with AN, 54 adolescents with BN, and 40 adolescents with MDD. Adolescents with at least one parent completed the Standardized Clinical Family Interview. Adolescents completed structured diagnostic interviews to assess eligibility for the study, as well as a standardized questionnaire to assess depression. RESULTS: Analyses revealed that fathers showed higher levels of critical comments to adolescents with BN or MDD than those with AN, whereas mothers made more critical comments toward patients with BN. Mothers made the least number of positive remarks toward patients with MDD. In terms of the influence of family status, fathers from intact families showed more expressions of warmth and were less critical than fathers from nonintact families, whereas mothers from intact families were less critical but also made fewer positive remarks than mothers from nonintact families. The presence of siblings appeared to reduce mothers' expression of warmth and emotional overinvolvement. CONCLUSIONS: Unique patterns of EE were found to characterize AN, BN, and MDD. Family status and the presence of siblings exert an influence on EE that should be taken into consideration in future research. PMID- 27377708 TI - Blocked Shape Memory Effect in Negative Poisson's Ratio Polymer Metamaterials. AB - We describe a new class of negative Poisson's ratio (NPR) open cell PU-PE foams produced by blocking the shape memory effect in the polymer. Contrary to classical NPR open cell thermoset and thermoplastic foams that return to their auxetic phase after reheating (and therefore limit their use in technological applications), this new class of cellular solids has a permanent negative Poisson's ratio behavior, generated through multiple shape memory (mSM) treatments that lead to a fixity of the topology of the cell foam. The mSM-NPR foams have Poisson's ratio values similar to the auxetic foams prior their return to the conventional phase, but compressive stress-strain curves similar to the ones of conventional foams. The results show that by manipulating the shape memory effect in polymer microstructures it is possible to obtain new classes of materials with unusual deformation mechanisms. PMID- 27377706 TI - Therapeutic efficacy and safety of Botulinum Toxin A Therapy in Trigeminal Neuralgia: a systematic review and meta-analysis of randomized controlled trials. AB - BACKGROUND: Several different interventions have been examined to alleviate pain and reduce frequency of trigeminal neuralgia (TN) paroxysms. However, some patients continue to have persistent or recurrent painful attacks. Using a systematic review and meta-analysis approach, we aimed to synthesize evidence from published randomized controlled trials (RCTs) regarding safety and efficacy of botulinum toxin type A (BTX-A) as a possible emerging choice of treatment for TN. METHODS: We conducted an electronic search in 10 databases/electronic search engines to access relevant publications. All articles in all languages reporting RCTs on the efficacy and safety of BTX-A in the treatment of TN were included for systematic review and meta-analysis. RESULTS: A total of four RCTs (n = 178) were identified for final meta-analysis. The overall effect favored BTX-A versus placebo in terms of proportion of responders (risk ratio RR = 2.87, 95 % confidence interval CI [1.76, 4.69], p <0.0001) with no significant detected heterogeneity (p = 0.31; I(2) = 4 %). Paroxysms frequency per day was significantly lower for BTX-A group (mean difference MD = -29.79, 95 % CI [ 38.50,-21.08], p <0.00001) with no significant heterogeneity (p = 0.21; I(2) = 36 %). CONCLUSION: Despite limited data, our results suggest that BTX-A may be an effective and safe treatment option for patients with TN. Further larger and well designed RCTs are encouraged to translate these findings into better clinical outcome and better quality of life for TN patients. PMID- 27377709 TI - Human beta-defensin-2 and -3 enhance pro-inflammatory cytokine expression induced by TLR ligands via ATP-release in a P2X7R dependent manner. AB - Our previous results indicate that HBD2 and HBD3 are chemotactic for a broad spectrum of leukocytes in a CCR6- and CCR2-dependent manner. In this study we report that pre-stimulation of primary human macrophages or THP-1 cells with HBD2 or HBD3 results in a synergistic, enhanced expression of pro-inflammatory cytokines and chemokines induced by TLR ligand re-stimulation. Experiments using specific inhibitors of the ATP-gated channel receptor P2X7 or its functional ligand ATP, suggest that the enhanced expression of pro-inflammatory cytokines and chemokines seems to be mediated by P2X7R. Furthermore, our data provide evidence that beta-defensins do not directly interact with P2X7R but rather induce the release of intracellular ATP. Interference with ATP release abrogated the synergistic effect mediated by HBD2 and HBD3 pre-stimulation in THP-1 cells. However, extracellular ATP alone seems not to be sufficient to elicit the enhanced synergistic effect on cytokine and chemokine expression observed by pre stimulation of primary human macrophages or THP-1 cells with HBD2 or HBD3. Collectively, our findings provide new insights into the molecular mechanisms how HBD2 and HBD3 interact with cells of myeloid origin and demonstrate their immuno modulating functions during innate immune responses. PMID- 27377707 TI - KYNA analogue SZR72 modifies CFA-induced dural inflammation- regarding expression of pERK1/2 and IL-1beta in the rat trigeminal ganglion. AB - BACKGROUND: Neurogenic inflammation has for decades been considered an important part of migraine pathophysiology. In the present study, we asked the question if administration of a novel kynurenic acid analogue (SZR72), precursor of an excitotoxin antagonist and anti-inflammatory substance, can modify the neurogenic inflammatory response in the trigeminal ganglion. METHODS: Inflammation in the trigeminal ganglion was induced by local dural application of Complete Freunds Adjuvant (CFA). Levels of phosphorylated MAP kinase pERK1/2 and IL-1beta expression in V1 region of the trigeminal ganglion were investigated using immunohistochemistry and Western blot. FINDINGS: Pretreatment with one dose of SZR72 abolished the CFA-induced pERK1/2 and IL-1beta activation in the trigeminal ganglion. No significant change was noted in case of repeated treatment with SZR72 as compared to a single dose. CONCLUSIONS: This is the first study that demonstrates that one dose of KYNA analog before application of CFA can give anti inflammatory response in a model of trigeminal activation, opening a new line for further investigations regarding possible effects of KYNA derivates. PMID- 27377711 TI - Novel Regulation of Wnt Signaling at the Proximal Membrane Level. AB - Wnt pathways are crucial for embryonic development and adult tissue homeostasis in all multicellular animals. Our understanding of Wnt signaling networks has grown increasingly complex. Recent studies have revealed many regulatory proteins that function at the proximal membrane level to fine-tune signaling output and enhance signaling specificity. These proteins regulate crucial points in Wnt signaling, including post-translational modification of Wnt proteins, regulation of Wnt receptor degradation, internalization of Wnt receptor complex, and specific ligand-receptor complex formation. Such regulators not only provide us with molecular details of Wnt regulation but also serve as potential targets for therapeutic intervention. In this review we highlight new insights into Wnt regulation at the plasma membrane, especially newly identified feedback regulators. PMID- 27377710 TI - The collectins CL-L1, CL-K1 and CL-P1, and their roles in complement and innate immunity. AB - Both the complement system and collectins play important roles in our innate immune system. The collectins, which are characterized by their inclusion of a collagen-like region and a calcium-dependent carbohydrate recognition domain, are pattern recognition molecules and include the well characterized proteins mannan binding lectin (MBL) and the surfactant proteins SP-A/-D. Collectin liver 1 (CL L1), collectin kidney 1 (CL-K1) and collectin placenta 1 (CL-P1) are the most recently discovered collectins. Although their function is still under investigation, accumulating information suggests that CL-L1, CL-K1 and CL-P1 play important roles in host defense by recognizing a variety of microorganisms and interacting with effector proteins, including complement components. The recent establishment of the existence of CL-K1 in the circulation in form of heteromeric complexes with CL-L1 (known as CL-LK) and its activation of the lectin pathway via MASPs, drew new attention in the complement biology, which was further strengthened by the observed interactions between CL-P1 and CRP-C1q-factor H or properdin. Deficiency of either CL-K1 or MASP-3 has been demonstrated in 3MC syndrome patients with developmental abnormalities, showing that lectin pathway components, regulation and/or activation are essential during the embryonic development; another feature that they most likely share CL-P1. Herein, we discuss the recent characteristics and roles of the collectins CL-L1, CL-K1 and CL-P1 in the complement system, in innate immunity and their possible association with disease development and pathogenesis. PMID- 27377712 TI - The different roles of a cationic gold(i) complex in catalysing hydroarylation of alkynes and alkenes with a heterocycle. AB - The mechanism of twofold hydroarylation of terminal alkynes with pyrrole catalyzed by a cationic gold(i) complex was investigated using DFT. It was found that while both the hydroarylation reactions proceed via a Friedel-Crafts-type mechanism, the first hydroarylation is directly promoted by gold(i) but the second hydroarylation by a proton released through interaction of the alkene product with gold-bound acidic organic species such as acetic acid and terminal alkynes. PMID- 27377713 TI - Current practice in regional anaesthesia in South America: An online survey. AB - OBJECTIVE: A survey was conducted in order to obtain a profile of the practice of regional anesthesia in South America, and determine the limitations of its use. METHODS: After institutional ethics committee approval, a link to an online questionnaire was sent by e-mail to anaesthesiologists in Argentina, Bolivia, Chile, Colombia, Panama, Paraguay, Peru, and Uruguay. The questionnaire was processed anonymously. RESULTS: A total of 1,260 completed questionnaires were received. The results showed that 97.6% of the anaesthesiologists that responded used regional anaesthesia in clinical practice, 66.9% performed peripheral nerve block (PNB) regularly, 21.6% used continuous PNB techniques, and 4.6% used stimulating catheters. The primary source of training was residency programs. As regards PNB, the most common performed were interscalene (52.3%), axillary (45.1%), femoral (43.2%), and ankle block (43%). As regards the localisation technique employed, 16% used paraesthesia, 44.2% used a peripheral nerve stimulator, and 18.1% ultrasound guidance. CONCLUSIONS: Regional anaesthesia and PNB are commonly used among South American anaesthesiologists. Considering that each country has its own profile for use, this profile should guide training in clinical practice, especially in residency programs. PMID- 27377715 TI - Improved 6-Plex Tandem Mass Tags Quantification Throughput Using a Linear Ion Trap-High-Energy Collision Induced Dissociation MS(3) Scan. AB - The use of tandem mass tags (TMT) as an isobaric labeling strategy is a powerful method for quantitative proteomics, yet its accuracy has traditionally suffered from interference. This interference can be largely overcome by selecting MS(2) fragment precursor ions for high-energy collision induced dissociation (HCD) MS(3) analysis in an Orbitrap scan. While this approach minimizes the interference effect, sensitivity suffers due to the high AGC targets and long acquisition times associated with MS(3) Orbitrap detection. We investigated whether acquiring the MS(3) scan in a linear ion trap with its lower AGC target would increase overall quantification levels with a minimal effect on precision and accuracy. Trypsin-digested proteins from Saccharomyces cerevisiae were tagged with 6-plex TMT reagents. The sample was subjected to replicate analyses using either the Orbitrap or the linear ion trap for the HCD MS(3) scan. HCD MS(3) detection in the linear ion trap vs Orbitrap increased protein identification by 66% with minor loss in precision and accuracy. Thus, the use of a linear ion trap HCD MS(3) scan during a 6-plex TMT experiment can improve overall identification levels while maintaining the power of multiplexed quantitative analysis. PMID- 27377716 TI - Extranodal diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow up. PMID- 27377717 TI - Pharmacogenomic and personalized approaches to tackle nonalcoholic fatty liver disease. AB - Nonalcoholic fatty liver disease (NAFLD) is a raising liver disease with increasing prevalence due to the epidemics of obesity and diabetes, with end points in cirrhosis or hepatocellular carcinoma. A multitude of genetic and metabolic perturbations, together with environmental factors, likely drive the disease. However, to date only a few genes, primarily PNPLA3 and TM6SF2, associate with NAFLD and there is no specific treatment. In this review we focus on the therapeutical aspects of NAFLD, taking into account drugs and lifestyle interventions. Sex also influences disease progression and treatment outcomes. Lastly, we discuss the present and potential future of personalized approaches to tackle NAFLD and how the known polymorphisms of NAFLD associated genes influence the choice and success of therapy. PMID- 27377718 TI - Store-operated Ca2+ channels in airway epithelial cell function and implications for asthma. AB - The epithelial cells of the lung are at the interface of a host and its environment and are therefore directly exposed to the inhaled air-borne particles. Rather than serving as a simple physical barrier, airway epithelia detect allergens and other irritants and then help organize the subsequent immune response through release of a plethora of secreted signals. Many of these signals are generated in response to opening of store-operated Ca(2+) channels in the plasma membrane. In this review, we describe the properties of airway store operated channels and their role in regulating airway epithelial cell function.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID- 27377719 TI - Ca2+ toxicity and mitochondrial damage in acute pancreatitis: translational overview. AB - Acute pancreatitis (AP) is a leading cause of hospitalization among non-malignant gastrointestinal disorders. The mortality of severe AP can reach 30-50%, which is most probably owing to the lack of specific treatment. Therefore, AP is a major healthcare problem, which urges researchers to identify novel drug targets. Studies from the last decades highlighted that the toxic cellular Ca(2+) overload and mitochondrial damage are key pathogenic steps in the disease development affecting both acinar and ductal cell functions. Moreover, recent observations showed that modifying the cellular Ca(2+) signalling might be beneficial in AP. The inhibition of Ca(2+) release from the endoplasmic reticulum or the activity of plasma membrane Ca(2+) influx channels decreased the severity of AP in experimental models. Similarly, inhibition of mitochondrial permeability transition pore (MPTP) opening also seems to improve the outcome of AP in in vivo animal models. At the moment MPTP blockers are under detailed clinical investigation to test whether interventions in MPTP openings and/or Ca(2+) homeostasis of the cells can be specific targets in prevention or treatment of cell damage in AP.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID- 27377720 TI - Running out of time: the decline of channel activity and nucleotide activation in adenosine triphosphate-sensitive K-channels. AB - KATP channels act as key regulators of electrical excitability by coupling metabolic cues-mainly intracellular adenine nucleotide concentrations-to cellular potassium ion efflux. However, their study has been hindered by their rapid loss of activity in excised membrane patches (rundown), and by a second phenomenon, the decline of activation by Mg-nucleotides (DAMN). Degradation of PI(4,5)P2 and other phosphoinositides is the strongest candidate for the molecular cause of rundown. Broad evidence indicates that most other determinants of rundown (e.g. phosphorylation, intracellular calcium, channel mutations that affect rundown) also act by influencing KATP channel regulation by phosphoinositides. Unfortunately, experimental conditions that reproducibly prevent rundown have remained elusive, necessitating post hoc data compensation. Rundown is clearly distinct from DAMN. While the former is associated with pore-forming Kir6.2 subunits, DAMN is generally a slower process involving the regulatory sulfonylurea receptor (SUR) subunits. We speculate that it arises when SUR subunits enter non-physiological conformational states associated with the loss of SUR nucleotide-binding domain dimerization following prolonged exposure to nucleotide-free conditions. This review presents new information on both rundown and DAMN, summarizes our current understanding of these processes and considers their physiological roles.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID- 27377721 TI - P2X receptors. AB - Extracellular adenosine 5'-triphosphate (ATP) activates cell surface P2X and P2Y receptors. P2X receptors are membrane ion channels preferably permeable to sodium, potassium and calcium that open within milliseconds of the binding of ATP. In molecular architecture, they form a unique structural family. The receptor is a trimer, the binding of ATP between subunits causes them to flex together within the ectodomain and separate in the membrane-spanning region so as to open a central channel. P2X receptors have a widespread tissue distribution. On some smooth muscle cells, P2X receptors mediate the fast excitatory junction potential that leads to depolarization and contraction. In the central nervous system, activation of P2X receptors allows calcium to enter neurons and this can evoke slower neuromodulatory responses such as the trafficking of receptors for the neurotransmitter glutamate. In primary afferent nerves, P2X receptors are critical for the initiation of action potentials when they respond to ATP released from sensory cells such as taste buds, chemoreceptors or urothelium. In immune cells, activation of P2X receptors triggers the release of pro inflammatory cytokines such as interleukin 1beta. The development of selective blockers of different P2X receptors has led to clinical trials of their effectiveness in the management of cough, pain, inflammation and certain neurodegenerative diseases.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID- 27377723 TI - Impairments of neural circuit function in Alzheimer's disease. AB - An essential feature of Alzheimer's disease (AD) is the accumulation of amyloid beta (Abeta) peptides in the brain, many years to decades before the onset of overt cognitive symptoms. We suggest that during this very extended early phase of the disease, soluble Abeta oligomers and amyloid plaques alter the function of local neuronal circuits and large-scale networks by disrupting the balance of synaptic excitation and inhibition (E/I balance) in the brain. The analysis of mouse models of AD revealed that an Abeta-induced change of the E/I balance caused hyperactivity in cortical and hippocampal neurons, a breakdown of slow wave oscillations, as well as network hypersynchrony. Remarkably, hyperactivity of hippocampal neurons precedes amyloid plaque formation, suggesting that hyperactivity is one of the earliest dysfunctions in the pathophysiological cascade initiated by abnormal Abeta accumulation. Therapeutics that correct the E/I balance in early AD may prevent neuronal dysfunction, widespread cell loss and cognitive impairments associated with later stages of the disease.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID- 27377724 TI - Effect of knockout of alpha2delta-1 on action potentials in mouse sensory neurons. AB - Gene deletion of the voltage-gated calcium channel auxiliary subunit alpha2delta 1 has been shown previously to have a cardiovascular phenotype, and a reduction in mechano- and cold sensitivity, coupled with delayed development of neuropathic allodynia. We have also previously shown that dorsal root ganglion (DRG) neuron calcium channel currents were significantly reduced in alpha2delta-1 knockout mice. To extend our findings in these sensory neurons, we have examined here the properties of action potentials (APs) in DRG neurons from alpha2delta-1 knockout mice in comparison to their wild-type (WT) littermates, in order to dissect how the calcium channels that are affected by alpha2delta-1 knockout are involved in setting the duration of individual APs and their firing frequency. Our main findings are that there is reduced Ca(2+) entry on single AP stimulation, particularly in the axon proximal segment, reduced AP duration and reduced firing frequency to a 400 ms stimulation in alpha2delta-1 knockout neurons, consistent with the expected role of voltage-gated calcium channels in these events. Furthermore, lower intracellular Ca(2+) buffering also resulted in reduced AP duration, and a lower frequency of AP firing in WT neurons, mimicking the effect of alpha2delta-1 knockout. By contrast, we did not obtain any consistent evidence for the involvement of Ca(2+)-activation of large conductance calcium-activated potassium (BK) and small conductance calcium-activated potassium (SK) channels in these events. In conclusion, the reduced Ca(2+) elevation as a result of single AP stimulation is likely to result from the reduced duration of the AP in alpha2delta-1 knockout sensory neurons.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID- 27377722 TI - The homeostatic astroglia emerges from evolutionary specialization of neural cells. AB - Evolution of the nervous system progressed through cellular diversification and specialization of functions. Conceptually, the nervous system is composed from electrically excitable neuronal networks connected with chemical synapses and non excitable glial cells that provide for homeostasis and defence. Astrocytes are integrated into neural networks through multipartite synapses; astroglial perisynaptic processes closely enwrap synaptic contacts and control homeostasis of the synaptic cleft, supply neurons with glutamate and GABA obligatory precursor glutamine and contribute to synaptic plasticity, learning and memory. In neuropathology, astrocytes may undergo reactive remodelling or degeneration; to a large extent, astroglial reactions define progression of the pathology and neurological outcome.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID- 27377725 TI - Acid-sensing ion channels regulate spontaneous inhibitory activity in the hippocampus: possible implications for epilepsy. AB - Acid-sensing ion channels (ASICs) play an important role in numerous functions in the central and peripheral nervous systems ranging from memory and emotions to pain. The data correspond to a recent notion that each neuron and many glial cells of the mammalian brain express at least one member of the ASIC family. However, the mechanisms underlying the involvement of ASICs in neuronal activity are poorly understood. However, there are two exceptions, namely, the straightforward role of ASICs in proton-based synaptic transmission in certain brain areas and the role of the Ca(2+)-permeable ASIC1a subtype in ischaemic cell death. Using a novel orthosteric ASIC antagonist, we have found that ASICs specifically control the frequency of spontaneous inhibitory synaptic activity in the hippocampus. Inhibition of ASICs leads to a strong increase in the frequency of spontaneous inhibitory postsynaptic currents. This effect is presynaptic because it is fully reproducible in single synaptic boutons attached to isolated hippocampal neurons. In concert with this observation, inhibition of the ASIC current diminishes epileptic discharges in a low Mg(2+) model of epilepsy in hippocampal slices and significantly reduces kainate-induced discharges in the hippocampus in vivo Our results reveal a significant novel role for ASICs.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID- 27377726 TI - Intertwining extracellular nucleotides and their receptors with Ca2+ in determining adult neural stem cell survival, proliferation and final fate. AB - In the central nervous system (CNS), during both brain and spinal cord development, purinergic and pyrimidinergic signalling molecules (ATP, UTP and adenosine) act synergistically with peptidic growth factors in regulating the synchronized proliferation and final specification of multipotent neural stem cells (NSCs) to neurons, astrocytes or oligodendrocytes, the myelin-forming cells. Some NSCs still persist throughout adulthood in both specific 'neurogenic' areas and in brain and spinal cord parenchyma, retaining the potentiality to generate all the three main types of adult CNS cells. Once CNS anatomical structures are defined, purinergic molecules participate in calcium-dependent neuron-to-glia communication and also control the behaviour of adult NSCs. After development, some purinergic mechanisms are silenced, but can be resumed after injury, suggesting a role for purinergic signalling in regeneration and self repair also via the reactivation of adult NSCs. In this respect, at least three different types of adult NSCs participate in the response of the adult brain and spinal cord to insults: stem-like cells residing in classical neurogenic niches, in particular, in the ventricular-subventricular zone (V-SVZ), parenchymal oligodendrocyte precursor cells (OPCs, also known as NG2-glia) and parenchymal injury-activated astrocytes (reactive astrocytes). Here, we shall review and discuss the purinergic regulation of these three main adult NSCs, with particular focus on how and to what extent modulation of intracellular calcium levels by purinoceptors is mandatory to determine their survival, proliferation and final fate.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID- 27377728 TI - Calcium and ATP control multiple vital functions. AB - Life on Planet Earth, as we know it, revolves around adenosine triphosphate (ATP) as a universal energy storing molecule. The metabolism of ATP requires a low cytosolic Ca(2+) concentration, and hence tethers these two molecules together. The exceedingly low cytosolic Ca(2+) concentration (which in all life forms is kept around 50-100 nM) forms the basis for a universal intracellular signalling system in which Ca(2+) acts as a second messenger. Maintenance of transmembrane Ca(2+) gradients, in turn, requires ATP-dependent Ca(2+) transport, thus further emphasizing the inseparable links between these two substances. Ca(2+) signalling controls the most fundamental processes in the living organism, from heartbeat and neurotransmission to cell energetics and secretion. The versatility and plasticity of Ca(2+) signalling relies on cell specific Ca(2+) signalling toolkits, remodelling of which underlies adaptive cellular responses. Alterations of these Ca(2+) signalling toolkits lead to aberrant Ca(2+) signalling which is fundamental for the pathophysiology of numerous diseases from acute pancreatitis to neurodegeneration. This paper introduces a theme issue on this topic, which arose from a Royal Society Theo Murphy scientific meeting held in March 2016.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID- 27377727 TI - Vitamin D, reactive oxygen species and calcium signalling in ageing and disease. AB - Vitamin D is a hormone that maintains healthy cells. It functions by regulating the low resting levels of cell signalling components such as Ca(2+) and reactive oxygen species (ROS). Its role in maintaining phenotypic stability of these signalling pathways depends on the ability of vitamin D to control the expression of those components that act to reduce the levels of both Ca(2+) and ROS. This regulatory role of vitamin D is supported by both Klotho and Nrf2. A decline in the vitamin D/Klotho/Nrf2 regulatory network may enhance the ageing process, and this is well illustrated by the age-related decline in cognition in rats that can be reversed by administering vitamin D. A deficiency in vitamin D has also been linked to two of the major diseases in man: heart disease and Alzheimer's disease (AD). In cardiac cells, this deficiency alters the Ca(2+) transients to activate the gene transcriptional events leading to cardiac hypertrophy and the failing heart. In the case of AD, it is argued that vitamin D deficiency results in the Ca(2+) landscape that initiates amyloid formation, which then elevates the resting level of Ca(2+) to drive the memory loss that progresses to neuronal cell death and dementia.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID- 27377730 TI - The zinc sensing receptor, ZnR/GPR39, triggers metabotropic calcium signalling in colonocytes and regulates occludin recovery in experimental colitis. AB - Impaired epithelial barrier function is a hallmark of inflammatory bowel diseases, such as colitis, contributing to diarrhoea and perpetuating inflammation. We show that the zinc sensing receptor, ZnR/GPR39, triggers intracellular Ca(2+) signalling in colonocytes thereby inducing occludin expression. Moreover, ZnR/GPR39 is essential for epithelial barrier recovery in the dextran sodium sulfate (DSS) ulcerative colitis model. Loss of ZnR/GPR39 results in increased susceptibility to DSS-induced inflammation, owing to low expression of the tight junction protein occludin and impaired epithelial barrier. Recovery of wild-type (WT) mice from the DSS insult was faster than that of ZnR/GPR39 knockout (KO) mice. Enhanced recovery of the epithelial layer and increased crypt regeneration were observed in WT mice compared with ZnR/GPR39 KO, suggesting that ZnR/GPR39 is promoting epithelial barrier integrity following DSS insult. Indeed, cell proliferation and apical expression of occludin, following the DSS-induced epithelial erosion, were increased in WT tissue but not in ZnR/GPR39 KO tissue. Importantly, survival following DSS treatment was higher in WT mice compared with ZnR/GPR39 KO mice. Our results support a direct role for ZnR/GPR39 in promoting epithelial renewal and barrier function following DSS treatment, thereby affecting the severity of the disease. We suggest ZnR/GPR39 as a novel therapeutic target that can improve epithelial barrier function in colitis.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID- 27377732 TI - Calcium and adenosine triphosphate control of cellular pathology: asparaginase induced pancreatitis elicited via protease-activated receptor 2. AB - Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca(2+) signals, occurring as repetitive short lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca(2+) elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca(2+) signals can be evoked by products of alcohol and fatty acids as well as bile acids. Here, we have investigated the mechanism by which l-asparaginase evokes AP. Asparaginase is an essential element in the successful treatment of acute lymphoblastic leukaemia, the most common type of cancer affecting children, but AP is a side effect occurring in about 5-10% of cases. Like other pancreatitis-inducing agents, asparaginase evoked intracellular Ca(2+) release followed by Ca(2+) entry and also substantially reduced Ca(2+) extrusion because of decreased intracellular ATP levels. The toxic Ca(2+) signals caused extensive necrosis. The asparaginase-induced pathology depended on protease-activated receptor 2 and its inhibition prevented the toxic Ca(2+) signals and necrosis. We tested the effects of inhibiting the Ca(2+) release-activated Ca(2+) entry by the Ca(2+) channel inhibitor GSK-7975A. This markedly reduced asparaginase-induced Ca(2+) entry and also protected effectively against the development of necrosis.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID- 27377729 TI - Inseparable tandem: evolution chooses ATP and Ca2+ to control life, death and cellular signalling. AB - From the very dawn of biological evolution, ATP was selected as a multipurpose energy-storing molecule. Metabolism of ATP required intracellular free Ca(2+) to be set at exceedingly low concentrations, which in turn provided the background for the role of Ca(2+) as a universal signalling molecule. The early-eukaryote life forms also evolved functional compartmentalization and vesicle trafficking, which used Ca(2+) as a universal signalling ion; similarly, Ca(2+) is needed for regulation of ciliary and flagellar beat, amoeboid movement, intracellular transport, as well as of numerous metabolic processes. Thus, during evolution, exploitation of atmospheric oxygen and increasingly efficient ATP production via oxidative phosphorylation by bacterial endosymbionts were a first step for the emergence of complex eukaryotic cells. Simultaneously, Ca(2+) started to be exploited for short-range signalling, despite restrictions by the preset phosphate-based energy metabolism, when both phosphates and Ca(2+) interfere with each other because of the low solubility of calcium phosphates. The need to keep cytosolic Ca(2+) low forced cells to restrict Ca(2+) signals in space and time and to develop energetically favourable Ca(2+) signalling and Ca(2+) microdomains. These steps in tandem dominated further evolution. The ATP molecule (often released by Ca(2+)-regulated exocytosis) rapidly grew to be the universal chemical messenger for intercellular communication; ATP effects are mediated by an extended family of purinoceptors often linked to Ca(2+) signalling. Similar to atmospheric oxygen, Ca(2+) must have been reverted from a deleterious agent to a most useful (intra- and extracellular) signalling molecule. Invention of intracellular trafficking further increased the role for Ca(2+) homeostasis that became critical for regulation of cell survival and cell death. Several mutually interdependent effects of Ca(2+) and ATP have been exploited in evolution, thus turning an originally unholy alliance into a fascinating success story.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID- 27377734 TI - The Efficiency of Intravenous Iron Therapy in Korean Inflammatory Bowel Disease Patients. PMID- 27377731 TI - Short- and long-term (trophic) purinergic signalling. AB - There is long-term (trophic) purinergic signalling involving cell proliferation, differentiation, motility and death in the development and regeneration of most systems of the body, in addition to fast purinergic signalling in neurotransmission, neuromodulation and secretion. It is not always easy to distinguish between short- and long-term signalling. For example, adenosine triphosphate (ATP) can sometimes act as a short-term trigger for long-term trophic events that become evident days or even weeks after the original challenge. Examples of short-term purinergic signalling during sympathetic, parasympathetic and enteric neuromuscular transmission and in synaptic transmission in ganglia and in the central nervous system are described, as well as in neuromodulation and secretion. Long-term trophic signalling is described in the immune/defence system, stratified epithelia in visceral organs and skin, embryological development, bone formation and resorption and in cancer. It is likely that the increase in intracellular Ca(2+) in response to both P2X and P2Y purinoceptor activation participates in many short- and long-term physiological effects.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID- 27377735 TI - Is Elderly Age a Simple Predictive Factor for Inadequate Bowel Preparation before Colonoscopy? PMID- 27377733 TI - Alterations of p14 ARF , p15 INK4b , and p16 INK4a Genes in Primary Laryngeal Squamous Cell Carcinoma. AB - The 9p21 gene cluster, harboring growth suppressive genes p14 ARF , p15 INK4b , and p16 INK4a , is one of the major aberration hotspots in head and neck cancers. We try to elucidate specific aberrations affecting this region, throughout methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. Methylation of the gene was investigated by MS-MLPA in a well characterized series of 27 laryngeal squamous cell carcinomas and 20 samples of healthy mucosa. Aberrant promoter hypermethylation was confirmed using and methylation-specific. All samples studied except 3 (11 %) presented losses at 9p21 segment. The most common finding was the small deletion (exon 1alpha) of the p16 INK4a locus (44 %). Deletion of the 9p21 gene cluster was identified in 5 cases (18 %). We only found methylation in 8 samples (30 %) for p15 IK4b -exon 1. Promoter methylation of p14 ARF , p15 IK4b and p16 INK4a was not detected in any tumor sample. Methylation-specific polymerase chain reaction confirmed the results. Our data indicate that there may be a subgroup of patients in which epigenetic regulation of 9p21 segment might have little relevance. Nevertheless, MS-MLPA could not be suitable for the study of methylation at this region and further research is required. PMID- 27377736 TI - Serum Procalcitonin Is a Candidate Biomarker to Differentiate Bacteremia from Disease Flares in Patients with Inflammatory Bowel Disease. PMID- 27377737 TI - Proton Pump Inhibitors Should be Used with Caution in Critically Ill Patients to Prevent the Risk of Clostridium difficile Infection. PMID- 27377738 TI - Towards Steroid-Free Immunosuppression after Liver Transplantation. PMID- 27377739 TI - Is There Room for Improvement in Increasing the Stent Patency of Biliary Plastic Stents? PMID- 27377740 TI - Navigating the Microbial Basis of Inflammatory Bowel Diseases: Seeing the Light at the End of the Tunnel. AB - Inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis, are chronic inflammatory conditions affecting the gastrointestinal tract with variable presentations and disease courses. The cause of IBD is unknown, but it is hypothesized that individuals with a genetic predisposition to disease develop an aberrant immune response to environmental triggers. Evidence suggests that microbiota residing in the gastrointestinal tract play an important role in the development and perpetuation of the disease. In this review, we discuss the role of microbes in the development of a healthy gut, their role in the development of diseases in general, and their role in the development of IBD. Advances in molecular technologies and bioinformatics will continue to further our insight into the structure of the microbial community, the function of the microbial community as a whole, and the interaction of this community with the host immune system. The latter two are crucial to understanding the role of microbes in IBD. The field has advanced significantly in recent years, and the future is very promising as we begin to elucidate the microbial basis of IBD. PMID- 27377741 TI - Evaluation and Management of Hepatic Encephalopathy: Current Status and Future Directions. AB - Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without liver injury. It can be divided into minimal (covert) hepatic encephalopathy and overt hepatic encephalopathy, depending on the severity. Patients with hepatic encephalopathy have compromised clinical outcomes, decreased quality of life, and increased healthcare utilization, often resulting in a heavy financial and personal burden on caregivers. The diagnosis remains largely clinical, with the exclusion of possible other causes for the altered mental status. Current treatment strategies include nonabsorbable disaccharides and antibiotics. This review will focus on the diagnosis, management and clinical impact of hepatic encephalopathy. PMID- 27377742 TI - Comparison of AIMS65 Score and Other Scoring Systems for Predicting Clinical Outcomes in Koreans with Nonvariceal Upper Gastrointestinal Bleeding. AB - BACKGROUND/AIMS: The AIMS65 score has not been sufficiently validated in Korea. The objective of this study was to compare the AIMS65 and other scoring systems for the prediction of various clinical outcomes in Korean patients with acute nonvariceal upper gastrointestinal bleeding (NVUGIB). METHODS: The AIMS65 score, clinical and full Rockall scores (cRS and fRS) and Glasgow-Blatchford (GBS) score were calculated in patients with NVUGIB in a single center retrospectively. The performance of these scores for predicting mortality, rebleeding, transfusion requirement, and endoscopic intervention was assessed by calculating the area under the receiver-operating characteristic curve. RESULTS: Of the 523 patients, 3.4% died within 30 days, 2.5% experienced rebleeding, 40.0% required endoscopic intervention, and 75.7% needed transfusion. The AIMS65 score was useful for predicting the 30-day mortality, the need for endoscopic intervention and for transfusion. The fRS was superior to the AIMS65, GBS, and cRS for predicting endoscopic intervention and the GBS was superior to the AIMS65, fRS, and cRS for predicting the transfusion requirement. CONCLUSIONS: The AIMS65 score was useful for predicting the 30-day mortality, transfusion requirement, and endoscopic intervention in Korean patients with acute NVUGIB. However, it was inferior to the GBS and fRS for predicting the transfusion requirement and endoscopic intervention, respectively. PMID- 27377743 TI - Erratum: Predicting Liver-Related Events Using Transient Elastography in Chronic Hepatitis C Patients with Sustained Virological Response. PMID- 27377744 TI - Endotoxin Tolerance Inhibits Degradation of Tumor Necrosis Factor Receptor Associated Factor 3 by Suppressing Pellino 1 Expression and the K48 Ubiquitin Ligase Activity of Cellular Inhibitor of Apoptosis Protein 2. AB - Pellino 1 positively regulates Toll-like receptor 4 signaling by regulating tumor necrosis factor receptor-associated factor 3 (TRAF3) degradation and is suppressed with the induction of endotoxin tolerance. However, the role of TRAF3 in endotoxin tolerance is largely unknown. In this study, we found that lipopolysaccharide (LPS) stimulation decreased TARF3 protein expression in mouse Kupffer cells (KCs) and liver tissues, whereas endotoxin tolerization abrogated this effect. Degradative TRAF3 K48-linked ubiquitination and the cytoplasmic translocation of the MYD88-associated multiprotein complex were significantly inhibited in tolerized KCs, which led to markedly impaired activation of MYD88 dependent JNK and p38 and downregulation of inflammatory cytokines. TRAF3 ablation failed to induce a fully endotoxin-tolerant state in RAW264.7 cells. Pellino 1 knockdown in Raw264.7 cells did not impair induction of cIAP2 in response to LPS but inhibited the K63-linked ubiquitination of cellular inhibitor of apoptosis protein 2 (cIAP2) and K48-linked ubiquitination of TRAF3 protein. We also found upregulation of Pellino 1 and downregulation of TRAF3 in liver tissues of patients with cholangitis. Our findings reveal a novel mechanism that endotoxin tolerance reprograms mitogen-activated protein kinase signaling by suppressing Pellino 1-mediated K63-linked ubiquitination of cIAP2, K48-linked ubiquitination, and degradation of TRAF3. PMID- 27377745 TI - Type III Secretion System of Pseudomonas aeruginosa Affects Matrix Metalloproteinase 12 (MMP-12) and MMP-13 Expression via Nuclear Factor kappaB Signaling in Human Carcinoma Epithelial Cells and a Pneumonia Mouse Model. AB - The type III secretion system (T3SS) in Pseudomonas aeruginosa has been linked to severe disease and poor clinical outcomes in animal and human studies. We aimed to investigate whether the ExoS and ExoT effector proteins of P. aeruginosa affect the expression of matrix metalloproteinase 12 (MMP-12) and MMP-13 via nuclear factor kappaB (NF-kappaB) signaling pathways. To understand the T3SS, we used DeltaExoS, DeltaExoT, and ExsA::Omega mutants, as well as P. aeruginosa strain K (PAK)-stimulated NCI-H292 cells. We investigated the effects of DeltaExoS, DeltaExoT, and ExsA::Omega on the development of pneumonia in mouse models. We examined the effects of DeltaExoS, DeltaExoT, and ExsA::Omega on MMP 12 and MMP-13 production in NCI-H292 cells. DeltaExoS and DeltaExoT markedly decreased the neutrophil count in bronchoalveolar lavage fluid, with a reduction in proinflammatory mediators, MMP-12, and MMP-13. DeltaExoS and DeltaExoT reduced NF-kappaB phosphorylation, together with MMP-12 and MMP-13 expression in PAK infected mouse models and NCI-H292 cells. To conclude, P. aeruginosa infection induced the expression of MMPs, and P. aeruginosa T3SS appeared to be a key player in MMP-12 and MMP-13 expression, which is further controlled by NF-kappaB signaling. These findings might be useful in devising a novel therapeutic approach to chronic pulmonary infections that involves decreasing the ExoS and ExoT levels. PMID- 27377747 TI - Erratum to: A method of extending the depth of focus of the high-resolution X-ray imaging system employing optical lens and scintillator: a phantom study. PMID- 27377746 TI - Ebola Virus Epidemiology and Evolution in Nigeria. AB - Containment limited the 2014 Nigerian Ebola virus (EBOV) disease outbreak to 20 reported cases and 8 fatalities. We present here clinical data and contact information for at least 19 case patients, and full-length EBOV genome sequences for 12 of the 20. The detailed contact data permits nearly complete reconstruction of the transmission tree for the outbreak. The EBOV genomic data are consistent with that tree. It confirms that there was a single source for the Nigerian infections, shows that the Nigerian EBOV lineage nests within a lineage previously seen in Liberia but is genetically distinct from it, and supports the conclusion that transmission from Nigeria to elsewhere did not occur. PMID- 27377748 TI - The influence of environmental variables on platelet concentration in horse platelet-rich plasma. AB - Platelet-rich plasma (PRP) commonly refers to blood products which contain a higher platelet (PLT) concentration as compared to normal plasma. Autologous PRP has been shown to be safe and effective in promoting the natural processes of soft tissue healing or reconstruction in humans and horses. Variability in PLT concentration has been observed in practice between PRP preparations from different patients or from the same individual under different conditions. A change in PLT concentration could modify PRP efficacy in routine applications. The aim of this study was to test the influence of environmental, individual and agonistic variables on the PLT concentration of PRP in horses. Six healthy Standardbred mares were exposed to six different variables with a one-week washout period between variables, and PRP was subsequently obtained from each horse. The variables were time of withdrawal during the day (morning/evening), hydration status (overhydration/dehydration) treatment with anti-inflammatory drugs and training periods on a treadmill. The platelet concentration was significantly higher in horses treated with a non-steroidal anti-inflammatory drug (P = 0.03). The leukocyte concentration increased 2-9 fold with respect to whole blood in the PRP which was obtained after exposure to all the variable considered. Environmental variation in platelet concentration should be taken into consideration during PRP preparation. PMID- 27377749 TI - Autocatalytic activation of a thermostable glutamyl endopeptidase capable of hydrolyzing proteins at high temperatures. AB - Glutamyl endopeptidases (GSEs) specifically hydrolyze peptide bonds formed by alpha-carboxyl groups of Glu and Asp residues. We cloned the gene for a thermophilic GSE (designated TS-GSE) from Thermoactinomyces sp. CDF. A proform of TS-GSE that contained a 61-amino acid N-terminal propeptide and a 218-amino acid mature domain was produced in Escherichia coli. We found that the proform possessed two processing sites and was capable of autocatalytic activation via multiple pathways. The N-terminal propeptide could be autoprocessed at the Glu-1 Ser1 bond to directly generate the mature enzyme. It could also be autoprocessed at the Glu-12-Lys-11 bond to yield an intermediate, which was then converted into the mature form after removal of the remaining part of the propeptide. The segment surrounding the two processing sites was flexible, which allowed the proform and the intermediate form to be trans-processed into the mature form by either active TS-GSE or heterogeneous proteases. Deletion analysis revealed that the N-terminal propeptide is important for the correct folding and maturation of TS-GSE. The propeptide, even its last 11-amino acid peptide segment, could inhibit the activity of its cognate mature domain. The mature TS-GSE displayed a temperature optimum of 85 degrees C and retained approximately 90 % of its original activity after incubation at 70 degrees C for 6 h, representing the most thermostable GSE reported to date. Mutational analysis suggested that the disulfide bonds Cys32-Cys48 and Cys180-Cys183 cumulatively contributed to the thermostability of TS-GSE. PMID- 27377750 TI - Elevated Cytosolic Cl- Concentrations in Dendritic Knobs of Mouse Vomeronasal Sensory Neurons. AB - In rodents, the vomeronasal system controls social and sexual behavior. However, several mechanistic aspects of sensory signaling in the vomeronasal organ remain unclear. Here, we investigate the biophysical basis of a recently proposed vomeronasal signal transduction component-a Ca(2+)-activated Cl(-) current. As the physiological role of such a current is a direct function of the Cl(-) equilibrium potential, we determined the intracellular Cl(-) concentration in dendritic knobs of vomeronasal neurons. Quantitative fluorescence lifetime imaging of a Cl(-)-sensitive dye at the apical surface of the intact vomeronasal neuroepithelium revealed increased cytosolic Cl(-) levels in dendritic knobs, a substantially lower Cl(-) concentration in vomeronasal sustentacular cells, and an apparent Cl(-) gradient in vomeronasal neurons along their dendritic apicobasal axis. Together, our data provide a biophysical basis for sensory signal amplification in vomeronasal neuron microvilli by opening Ca(2+)-activated Cl(-) channels. PMID- 27377751 TI - Organochlorine Pesticides in the Ferruginous Pygmy Owl (Glaucidium brasilianum) in Chiapas, Mexico. AB - Concentrations of organochlorine pesticides were quantified in samples of feathers (n = 17) and blood (n = 15) of the ferruginous pygmy owl (Glaucidium brasilianum). The individuals were captured near the Protected Natural Area Cerro Sonsonate, Chiapas, Mexico, between February and June 2014. In both tissues, pesticides belonging to seven organochlorine chemical families were detected. However, the organochlorine pesticide concentrations differed between feathers and blood. The highest concentrations of hexachlorocyclohexanes were found in feathers (0.63 +/- 0.89 MUg/g), whereas the highest concentrations of SigmaDrines were found in blood (0.31 +/- 0.47 MUg/mL). By using the summed concentrations for each of the seven families of pesticides found in feathers, we did not find any significant correlation between the pesticides and pectoral muscle or body weight (p > 0.15). The SigmaDDT group was the only pesticide family that showed a positive correlation with owl body weight (r = 0.60, p = 0.05); the concentrations of these pesticides were also high in feather and blood tissues (r = 0.87, p = 0.02). Our results confirm that ferruginous pygmy owls in the study area are exposed to these pesticides. PMID- 27377752 TI - Cadmium Uptake by Cuttings of Impatiens walleriana in Response to Different Cadmium Concentrations and Growth Periods. AB - Impatiens walleriana (I. walleriana), a potential cadmium (Cd) hyperaccumulator, can propagate by cuttings, which are less expensive to grow than seedlings. Different growth periods for cuttings, however, may lead to different physiological characteristics. In this study, I. walleriana cuttings were hydroponically grown in Cd-containing solutions (1.0-10.0 MUM) for various growth periods (10-60 days). Experimental results showed that the Cd treatments had negative effects on growth compared to the controls that were not spiked with Cd. The extension of the growth period promoted most of the growth exhibitions of I. walleriana, except for SPAD readings for cuttings grown in the 5.0 and 10.0 MUM solutions. The accumulation of Cd also increased over time, except in the roots of the cuttings grown in the 5.0 and 10.0 MUM solutions. The subcellular distribution and chemical forms of Cd showed that I. walleriana developed better tolerance and detoxification capacities in the cuttings grown in the 5.0 and 10.0 MUM solutions than in the cuttings grown in the other two Cd treatments. PMID- 27377753 TI - A case of lymphangioleiomyomatosis associated with endometrial cancer and severe systemic lupus erythematosus. AB - BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare idiopathic disorder that occurs in women of childbearing age, and consists of a diffuse proliferation of abnormal smooth muscle cells along the thoracic and abdominal lymphogenous route. CASE PRESENTATION: We experienced a case of a 47-yo woman with recent history of systemic lupus erythematosus (SLE) diagnosed with endometrial cancer, initially suspected to have metastasized to pelvic and para-aortic lymph nodes based on preoperative diagnostic imaging. Subsequent pathological diagnosis revealed stage IB endometrial cancer without evidence of lymph node involvement. Instead, enlarged pelvic and para-aortic lymph nodes were found to be due to extrapulmonary LAM, from a primary lesion found inside the uterine myometrium. SLE improved after surgery. CONCLUSION: This is the first reported case of comorbid endometrial cancer, SLE, and aggressive LAM metastasizing to regional lymph nodes, and strengthens the clinical evidence for a common role of mTOR pathway hyperactivity and estrogen responsiveness in the pathophysiology of metastasizing lesions of the genital tract. PMID- 27377754 TI - No association between the rs10503253 polymorphism in the CSMD1 gene and schizophrenia in a Han Chinese population. AB - BACKGROUND: Schizophrenia (SCZ) is a complex, heritable, and devastating psychiatric disorder. Recent genome-wide association studies have identified a single-nucleotide polymorphism (SNP; rs10503253) in the CUB and SUSHI multiple domains 1 (CSMD1) gene as a risk factor for SCZ. In this study, we investigated whether the rs10503253 in CSMD1 contributes to the risk of SCZ in a Han Chinese population. METHODS: We conducted a case-control study in a population from eastern China, involving 1378 SCZ patients and 1091 unrelated healthy controls, using the ligase detection reaction-polymerase chain reaction method to genotype the rs10503253 polymorphism in the CSMD1 gene. RESULTS: No significant association was found between the SCZ patients and controls for any allele or genotype frequency of the SNP rs10503253 (all P > 0.05). CONCLUSIONS: Our findings do not support an association between CSMD1 rs10503253 and SCZ in a Han Chinese population. PMID- 27377755 TI - Comprehensive RNA-Seq profiling to evaluate lactating sheep mammary gland transcriptome. AB - RNA-Seq enables the generation of extensive transcriptome information providing the capability to characterize transcripts (including alternative isoforms and polymorphism), to quantify expression and to identify differential regulation in a single experiment. Our aim in this study was to take advantage of using RNA-Seq high-throughput technology to provide a comprehensive transcriptome profiling of the sheep lactating mammary gland. Eight ewes of two dairy sheep breeds with differences in milk production traits were used in this experiment (four Churra and four Assaf ewes). Milk samples from these animals were collected on days 10, 50, 120 and 150 after lambing to cover the various physiological stages of the mammary gland across the complete lactation. RNA samples were extracted from milk somatic cells. The RNA-Seq dataset was generated using an Illumina HiSeq 2000 sequencer. The information reported here will be useful to understand the biology of lactation in sheep, providing also an opportunity to characterize their different patterns on milk production aptitude. PMID- 27377756 TI - Percutaneous alcohol septal ablation to acutely reduce left ventricular outflow tract obstruction induced by transcatheter mitral valve replacement. AB - Transcatheter implantation of balloon expandable valves in native mitral valves (MV) has been performed in patients with severe MV annular calcification who are not good candidates for standard surgical MV replacement. Significant left ventricular outflow tract (LVOT) obstruction with hemodynamic compromise has been described as one of the potential complications of transcatheter MV replacement. Surgical rescue carries significant risk in this high-risk patient population. We describe a percutaneous technique to acutely decrease transcatheter MV replacement-induced LVOT obstruction. (c) 2016 Wiley Periodicals, Inc. PMID- 27377757 TI - Effects of age and non-oropharyngeal proprioceptive and exteroceptive sensation on the magnitude of anticipatory mouth opening during eating. AB - To best prevent and treat eating/swallowing problems, it is essential to understand how components of oral physiology contribute to the preservation and/or degradation of eating/swallowing in healthy ageing. Anticipatory, pre swallow motor movements may be critical to safe and efficient eating/swallowing, particularly for older adults. However, the nature of these responses is relatively unknown. This study compared the magnitude of anticipatory mouth opening during eating in healthy older (aged 70-85) and younger (aged 18-30) adults under four eating conditions: typical self-feeding, typical assisted feeding (being fed by a research assistant resulting in proprioceptive loss), sensory loss self-feeding (wearing blindfold/headphones resulting in exteroceptive loss) and sensory loss assisted feeding (proprioceptive and exteroceptive loss). Older adults opened their mouths wider than younger adults in anticipation of food intake under both typical and most non-oropharyngeal sensory loss conditions. Further, the loss of proprioceptive and exteroceptive cues resulted in decreased anticipatory mouth opening for all participants. Greater mouth opening in older adults may be a protective compensation, contributing to the preservation of function associated with healthy ageing. Our finding that the loss of non-oropharyngeal sensory cues resulted in decreased anticipatory mouth opening highlights how important proprioception, vision, and hearing are in pre-swallow behaviour. Age- and disease-related changes in vision, hearing, and the ability to self-feed may reduce the effectiveness of these pre swallow strategies. PMID- 27377758 TI - Clinical evaluation of local hyperthermia at 44 degrees C for molluscum contagiosum: pilot study with 21 patients. PMID- 27377759 TI - No attentional capture from invisible flicker. AB - We tested whether fast flicker can capture attention using eight flicker frequencies from 20-96 Hz, including several too high to be perceived (>50 Hz). Using a 480 Hz visual display rate, we presented smoothly sampled sinusoidal temporal modulations at: 20, 30, 40, 48, 60, 69, 80, and 96 Hz. We first established flicker detection rates for each frequency. Performance was at or near ceiling until 48 Hz and dropped sharply to chance level at 60 Hz and above. We then presented the same flickering stimuli as pre-cues in a visual search task containing five elements. Flicker location varied randomly and was therefore congruent with target location on 20% of trials. Comparing congruent and incongruent trials revealed a very strong congruency effect (faster search for cued targets) for all detectable frequencies (20-48 Hz) but no effect for faster flicker rates that were detected at chance. This pattern of results (obtained with brief flicker cues: 58 ms) was replicated for long flicker cues (1000 ms) intended to allow for entrainment to the flicker frequency. These results indicate that only visible flicker serves as an exogenous attentional cue and that flicker rates too high to be perceived are completely ineffective. PMID- 27377760 TI - Investigation of the Coupled Effects of Molecular Weight and Charge-Transfer Interactions on the Optical and Photochemical Properties of Dissolved Organic Matter. AB - We studied the formation of photochemically produced reactive intermediates (RI) from dissolved organic matter (DOM). Specifically, we focused on the effects of variable molecular weight and chemical reduction on the optical properties of DOM (absorbance and fluorescence) and the formation of singlet oxygen ((1)O2), DOM triplet excited states ((3)DOM*), and the hydroxyl radical ((*)OH). The data are largely evaluated in terms of a charge-transfer (CT) model, but deficiencies in the model to explain the data are pointed out when evident. A total of two sets of samples were studied that were subjected to different treatments; the first set included secondary-treated wastewaters and a wastewater-impacted stream, and the second was a DOM isolate. Treatments included size fractionation and chemical reduction using sodium borohydride. Taken as a whole, the results demonstrate that decreasing molecular weight and borohydride reduction work in opposition regarding quantum efficiencies for (1)O2 and (3)DOM* production but in concert for fluorescence and (*)OH production. The optical and photochemical data provide evidence for a limited role of CT interactions occurring in lower-molecular weight DOM molecules. In addition, the data suggest that the observed optical and photochemical properties of DOM are a result of multiple populations of chromophores and that their relative contribution is changed by molecular-weight fractionation and borohydride reduction. PMID- 27377761 TI - Dog or chien? Translation equivalents in the receptive and expressive vocabularies of young French-English bilinguals. AB - In order to address gaps in the literature surrounding the acquisition of translation equivalents (TEs) in young bilinguals, two experiments were conducted. In Experiment 1, TEs were measured in the expressive vocabularies of thirty-four French-English bilinguals at 1;4, 1;10, and 2;6 using the MacArthur Bates CDI. Children's acquisition of TEs occurred gradually, with more balanced ratios of exposure and vocabulary associated with larger proportions of TEs at each wave. Experiment 2 compared a direct measure of TE comprehension with parent report of the same set of words. Results showed that parents may over-report children's TE comprehension, as our sample of two-year-old French-English bilinguals (n = 20) comprehended fewer TEs on a direct measure of receptive vocabulary than parents reported on the vocabulary checklist. The present study provides an original contribution to the literature on bilingual vocabulary development by employing both a longitudinal design and a direct measure of TE comprehension. PMID- 27377762 TI - Staphylococcus haemolyticus as a potential producer of biosurfactants with antimicrobial, anti-adhesive and synergistic properties. AB - Staphylococcus haemolyticus is an opportunistic human pathogen that usually gains entry into the host tissue in association with medical device contamination. Biofilm formation is a key factor for the establishment of this bacterium and its arrangement and dynamics can be influenced by the synthesis of biosurfactants. Biosurfactants are structurally diverse amphiphilic molecules with versatile biotechnological applications, but information on their production by staphylococci is still scarce. In this work, two Staph. haemolyticus strains, showing high potential for biosurfactant production - as observed by four complementary methods - were investigated. Biosurfactant extracts were produced and studied for their capacity to inhibit the growth and biofilm formation by other bacterial human pathogens. The biosurfactant produced by the one of the strains inhibited the growth of most bacteria tested and subinhibitory concentrations of the biosurfactant were able to decrease biofilm formation and showed synergistic effects with tetracycline. Because these results were also positive when the biosurfactants were tested against the producing strains, it is likely that biosurfactant production by Staph. haemolyticus may be an unexplored virulence factor, important for competition and biofilm formation by the bacterium, in addition to the biotechnological potential. SIGNIFICANCE AND IMPACT OF THE STUDY: This work is the first to show the production of biosurfactants by Staphylococcus haemolyticus strains. Extracts showed antimicrobial, anti-adhesive and synergistic properties against a variety of relevant human pathogens, including the producing strains. In addition to the biotechnological potential, biosurfactants produced by Staph. haemolyticus are potentially undescribed virulence determinants in their producing strains. PMID- 27377763 TI - Genome-scale DNA variant analysis and functional validation of a SNP underlying yellow fruit color in wild strawberry. AB - Fragaria vesca is a species of diploid strawberry being developed as a model for the octoploid garden strawberry. This work sequenced and compared the genomes of three F. vesca accessions: 'Hawaii 4', 'Rugen', and 'Yellow Wonder'. Genome-scale analyses of shared and distinct SNPs among these three accessions have revealed that 'Rugen' and 'Yellow Wonder' are more similar to each other than they are to 'Hawaii 4'. Though all three accessions are inbred seven generations, each accession still possesses extensive heterozygosity, highlighting the inherent differences between individual plants even of the same accession. The identification of the impact of each SNP as well as the large number of Indel markers provides a foundation for locating candidate mutations underlying phenotypic variations among these F. vesca accessions and for mapping new mutations generated through forward genetics screens. Through systematic analysis of SNP variants affecting genes in anthocyanin biosynthesis and regulation, a candidate SNP in FveMYB10 was identified and then functionally confirmed to be responsible for the yellow color fruits made by many F. vesca accessions. As a whole, this study provides further resources for F. vesca and establishes a foundation for linking traits of economic importance to specific genes and variants. PMID- 27377764 TI - Intensity of language treatment: contribution to children's language outcomes. AB - BACKGROUND: Treatment intensity is an important factor in designing and delivering treatments to children with language impairment (LI). However, to date very little is understood about cumulative intervention intensity for children with LI in the US public school system. AIMS: To examine treatment intensity (dose: time spent on language; frequency: number of sessions; duration: one academic year) as delivered to children with LI within US public schools and to explore its relation to children's language outcomes. METHODS & PROCEDURES: A total of 233 children with LI on the caseloads of 73 speech-language pathologists (SLPs) participated. Direct child measures, weekly treatment logs and videotapes were collected to characterize children's language outcomes and treatment experiences. OUTCOMES & RESULTS: Children on average received 36 min of treatment during 1.3 treatment sessions per week. Children's language severity did not predict children's treatment intensity. Structural equation modelling indicated a significant interaction between frequency and dose of treatment: children receiving high frequency and low dose, or low frequency and high dose treatment had better outcomes than children receiving high frequency, high dose or low frequency, low dose treatment. CONCLUSIONS & IMPLICATIONS: Findings suggest that more intensive language treatment, measured as time, is not necessarily associated with better treatment outcomes. PMID- 27377766 TI - Taming pathogenic gammadelta T cells with vitamin A. PMID- 27377765 TI - Mevalonate kinase deficiency leads to decreased prenylation of Rab GTPases. AB - Mevalonate kinase deficiency (MKD) is caused by mutations in a key enzyme of the mevalonate-cholesterol biosynthesis pathway, leading to recurrent autoinflammatory disease characterised by enhanced release of interleukin-1beta (IL-1beta). It is currently believed that the inflammatory phenotype of MKD is triggered by temperature-sensitive loss of mevalonate kinase activity and reduced biosynthesis of isoprenoid lipids required for the prenylation of small GTPase proteins. However, previous studies have not clearly shown any change in protein prenylation in patient cells under normal conditions. With lymphoblast cell lines from two compound heterozygous MKD patients, we used a highly sensitive in vitro prenylation assay, together with quantitative mass spectrometry, to reveal a subtle accumulation of unprenylated Rab GTPases in cells cultured for 3 days or more at 40 degrees C compared with 37 degrees C. This included a 200% increase in unprenylated Rab7A, Rab14 and Rab1A. Inhibition of sterol regulatory element binding protein (SREBP) activation by fatostatin led to more pronounced accumulation of unprenylated Rab proteins in MKD cells but not parent cells, suggesting that cultured MKD cells may partially overcome the loss of isoprenoid lipids by SREBP-mediated upregulation of enzymes required for isoprenoid biosynthesis. Furthermore, while inhibition of Rho/Rac/Rap prenylation promoted the release of IL-1beta, specific inhibition of Rab prenylation by NE10790 had no effect in human peripheral blood mononuclear cells or human THP-1 monocytic cells. These studies demonstrate for the first time that mutations in mevalonate kinase can lead to a mild, temperature-induced defect in the prenylation of small GTPases, but that loss of prenylated Rab GTPases is not the cause of enhanced IL 1beta release in MKD. PMID- 27377767 TI - Rabies awareness and dog ownership among rural northern and southern Chadian communities-Analysis of a community-based, cross-sectional household survey. AB - Canine rabies represents a major - but preventable - public health threat in Chad. In preparation for a nation-wide canine parenteral mass vaccination campaign we conducted a community-based, cross-sectional multi-stage cluster survey in 40 villages in two southern and two northern regions of Chad. Our objective was to investigate rabies awareness and dog-ownership among the rural population. Almost half of the households (45%) owned dogs, with an overall dog:human ratio of 1:7.8. Southern households owned almost two thirds (701/918) of all dogs and the number of dogs per household was twice as high compared to the north (2.7 vs. 1.3, respectively). This translates into a dog:human ratio of 1:5.2 in the south and 1:16.4 in the north. Only 76% of the respondents had heard of rabies. Respondents who (1) were male, (2)>19 years, (3) had primary education or higher and (4) were of Muslim faith were more likely to have heard of rabies (p<0.01). High level of rabies knowledge was positively associated with (1) southern residence, (2) any kind of education and (3) Christian or "other" religions. In contrast to rabies awareness, high level of knowledge was negatively associated with increasing age. 11% of respondents reported that at least one family member had been bitten by a dog in the past year and half of these bite victims were children. 31% of respondents knew someone who had died of rabies and twice as many (58%) reported having encountered a rabid animal. Most of the respondents could identify classical rabies symptoms (58-94%), however they lacked knowledge about rabies prevention and appropriate wound management. Only 2 out of 963 (0.5%) reported to have vaccinated their dog. A major proportion of our study population is at great risk of rabies (likely higher than 7 rabies death per million per year) due to lack of awareness of the disease, inappropriate post-bite treatment and insufficient knowledge about preventive measures. This reflects the urgent need for advocacy programs to raise rabies awareness among the community. Close intersectoral collaboration between the public health and veterinary sector and integration of local authorities, is a key element in the fight against rabies. PMID- 27377768 TI - Serological detection and epidemiology of Neospora caninum and Cryptosporidium parvum antibodies in cattle in southern Egypt. AB - Neospora caninum and Cryptosporidium parvum are intracellular protozoan parasites that are distributed worldwide and of major economical concern in cattle industry. N. caninum can cause abortion storms and high culling rates, whereas C. parvum has zoonotic implications and can cause diarrhea in calves. There are currently no data on the prevalence of neosporosis and cryptosporidiosis in humans or animals in southern Egypt. Prevalence of these two infections was determined in a sample of cattle from two different areas in southern Egypt, Sohag and Qena, using enzyme-linked immunosorbent assay. A total 301 cattle were sampled, of which 18.9% were positive for N. caninum, 35.9% were positive for C. parvum and 10.0% were positive for both. Geographical location and breeding system were considered as potential risk factors for C. parvum infection. A higher prevalence of infection was identified on small scale farms, compared with larger, intensive systems, with a prevalence of 50.2% compared with 37.8%, respectively. Animals in Sohag had a significantly higher prevalence compared with Qena, with a seroprevalence of 46.1% compared with 31.6%, respectively. In brief, marked seroprevalence recorded in this study indicates a high incidence of N. caninum and C. parvum infections in cattle, and this necessitates the application of more effective strategies for combating these types of infections on farms in Egypt. PMID- 27377769 TI - 'It's a bit too much fathering this seed': the meaning-making of the sperm donor in Italian lesbian mother families. AB - How do female-partnered mothers deal with the third-party involved in their reproductive arrangement? The aim of this study is to identify the meaning-making of the sperm donor, exploring different patterns between genetic and non-genetic mothers, as well as between open-identity and anonymous donation. Semi-structured interviews were conducted with 24 Italian female-partnered mothers, who at the time of data collection had at least one donor-conceived child. Interpretative Phenomenological Analysis was performed to identify emergent themes. None of the mothers considered the donor as the father of their child. Three patterns of thoughts and feelings recurred: 'donor as an entity', 'donor as a medical process', 'donor as a person'. Genetic and non-genetic mothers constructed shared meanings regarding the donor. Mothers who opted for anonymous donors were more likely to describe the donor as an entity and as a medical process compared with mothers who opted for open-identity donors. Different images of the donor lay beneath each meaning: respectively, donor as a ghost, donor as a place, donor as a kind man. Findings offer important insights for healthcare providers working in fertility clinics. They further suggest the most appropriate terms for third party reproduction and specific psychological counselling needs of prospective female-partnered mothers. PMID- 27377770 TI - Does slow embryo development predict a high aneuploidy rate on trophectoderm biopsy? AB - The aneuploidy rates in expanded blastocysts biopsied on days 5 and 6 development were assessed in women undergoing IVF followed by array comparative genomic hybridization. This study included 1171 expanded blastocysts from 465 patients. Among the 465 patients, 215 and 141 underwent embryo biopsy on day 5 and day 6 (46.2% and 30.3%, respectively), and 109 underwent biopsy on both days 5 and 6 (23.4%). The cycles of 206 women were cancelled because only aneuploidy embryos were present (44.3%). The aneuploid embryos were classified according to the type as single, double or complex aneuploidy. No differences were observed in the distributions of these three categories according to the day of the biopsy. The aneuploidy rate was also evaluated according to maternal age, and was found to be higher in older patients; however, no differences in this rate were detected between embryos biopsied on days 5 and 6 according to maternal age. Biopsy was carried out when blastocysts reached the expanded stage. The embryos biopsied on day 6 had a higher rate of aneuploidy (69.9%) than those biopsied on day 5 (61.4%); however, the euploid embryos transferred had similar chances for successful and healthy gestation. PMID- 27377771 TI - Small Players Ruling the Hard Game: siRNA in Bone Regeneration. PMID- 27377772 TI - Sclerostin Antibody Preserves the Morphology and Structure of Osteocytes and Blocks the Severe Skeletal Deterioration After Motor-Complete Spinal Cord Injury in Rats. PMID- 27377773 TI - Nonparametric inference on quantile lost lifespan. AB - In this article, the existing concept of reversed percentile residual life, or percentile inactivity time, is recast to show that it can be used for routine analysis of time-to-event data under right censoring to summarize "life lost," which poses several advantages over the existing methods for survival analysis. An estimating equation approach is adopted to avoid estimation of the probability density function of the underlying time-to-event distribution to estimate the variance of the quantile estimator. Additionally a K-sample test statistic is proposed to test the ratio of the quantile lost lifespans. Simulation studies are performed to assess finite properties of the proposed K-sample statistic in terms of coverage probability and power. The proposed method is illustrated with a real data example from a breast cancer study. PMID- 27377776 TI - Heat shock increases conjugation efficiency in Clostridium difficile. AB - Clostridium difficile infection has increased in incidence and severity over the past decade, and poses a unique threat to human health. However, genetic manipulation of C. difficile remains in its infancy and the bacterium remains relatively poorly characterised. Low-efficiency conjugation is currently the only available method for transfer of plasmid DNA into C. difficile. This is practically limiting and has slowed progress in understanding this important pathogen. Conjugation efficiency varies widely between strains, with important clinically relevant strains such as R20291 being particularly refractory to plasmid transfer. Here we present an optimised conjugation method in which the recipient C. difficile is heat treated prior to conjugation. This significantly improves conjugation efficiency in all C. difficile strains tested including R20291. Conjugation efficiency was also affected by the choice of media on which conjugations were performed, with standard BHI media giving most transconjugant recovery. Using our optimised method greatly increased the ease with which the chromosome of R20291 could be precisely manipulated by homologous recombination. Our method improves on current conjugation protocols and will help speed genetic manipulation of strains otherwise difficult to work with. PMID- 27377774 TI - Temperature mediates continental-scale diversity of microbes in forest soils. AB - Climate warming is increasingly leading to marked changes in plant and animal biodiversity, but it remains unclear how temperatures affect microbial biodiversity, particularly in terrestrial soils. Here we show that, in accordance with metabolic theory of ecology, taxonomic and phylogenetic diversity of soil bacteria, fungi and nitrogen fixers are all better predicted by variation in environmental temperature than pH. However, the rates of diversity turnover across the global temperature gradients are substantially lower than those recorded for trees and animals, suggesting that the diversity of plant, animal and soil microbial communities show differential responses to climate change. To the best of our knowledge, this is the first study demonstrating that the diversity of different microbial groups has significantly lower rates of turnover across temperature gradients than other major taxa, which has important implications for assessing the effects of human-caused changes in climate, land use and other factors. PMID- 27377777 TI - A case of multiple recurrence of Clostridium difficile infection with severe hematochezia in an immunocompromised host. AB - Clostridium difficile infection (CDI) is increasing in incidence and severity. Clinically, diarrhea frequently occurs, but severe hematochezia is rarely seen with CDI. We describe here a hematopoietic stem cell transplantation (HSCT) recipient who experienced life-threatening gastrointestinal bleeding due to severe CDI. Subsequent stool surveillance and molecular typing observed the patient who had two episodes of recurrence with a new strain of C. difficile distinct from the initial infection. We analyze C. difficile strains obtained from the patient, and also discuss the diagnosis and treatment of this case. PMID- 27377779 TI - Erratum to: Phenotypic differentiation of gastrointestinal microbes is reflected in their encoded metabolic repertoires. PMID- 27377778 TI - COL4A6 is dispensable for autosomal recessive Alport syndrome. AB - Alport syndrome is caused by mutations in the genes encoding alpha3, alpha4, or alpha5 (IV) chains. Unlike X-linked Alport mice, alpha5 and alpha6 (IV) chains are detected in the glomerular basement membrane of autosomal recessive Alport mice, however, the significance of this finding remains to be investigated. We therefore generated mice lacking both alpha3 and alpha6 (IV) chains and compared their renal function and survival with Col4a3 knockout mice of 129 * 1/Sv background. No significant difference was observed in the renal function or survival of the two groups, or when the mice were backcrossed once to C57BL/6 background. However, the survival of backcrossed double knockout mice was significantly longer than that of the mice of 129 * 1/Sv background, which suggests that other modifier genes were involved in this phenomenon. In further studies we identified two Alport patients who had a homozygous mutation in intron 46 of COL4A4. The alpha5 and alpha6 (IV) chains were focally detected in the glomerular basement membrane of these patients. These findings indicate that although alpha5 and alpha6 (IV) chains are induced in the glomerular basement membrane in autosomal recessive Alport syndrome, their induction does not seem to play a major compensatory role. PMID- 27377780 TI - Inhibitory nitrosylation of mammalian thioredoxin reductase 1: Molecular characterization and evidence for its functional role in cellular nitroso-redox imbalance. AB - Mammalian thioredoxin 1 (Trx1) and the selenoprotein Trx reductase 1 (TrxR1) are key cellular enzymes that function coordinately in thiol-based redox regulation and signaling. Recent studies have revealed that the Trx1/TrxR1 system has an S nitrosothiol reductase (denitrosylase) activity through which it can regulate nitric oxide-related cellular processes. In this study we revealed that TrxR1 is itself susceptible to nitrosylation, characterized the underlying mechanism, and explored its functional significance. We found that nitrosothiol or nitric oxide donating agents rapidly and effectively inhibited the activity of recombinant or endogenous TrxR1. In particular, the NADPH-reduced TrxR1 was partially and reversibly inhibited upon exposure to low concentrations (<10MUM) of S nitrosocysteine (CysNO) and markedly and continuously inhibited at higher doses. Concurrently, TrxR1 very efficiently reduced low, but not high, levels of CysNO. Biochemical and mass spectrometric analyses indicated that its active site selenocysteine residue renders TrxR1 highly susceptible to nitrosylation-mediated inhibition, and revealed both thiol and selenol modifications at the two redox active centers of the enzyme. Studies in HeLa cancer cells demonstrated that endogenous TrxR1 is sensitive to nitrosylation-dependent inactivation and pointed to an important role for glutathione in reversing or preventing this process. Notably, depletion of cellular glutathione with l-buthionine-sulfoximine synergized with nitrosating agents in promoting sustained nitrosylation and inactivation of TrxR1, events that were accompanied by significant oxidation of Trx1 and extensive cell death. Collectively, these findings expand our knowledge of the role and regulation of the mammalian Trx system in relation to cellular nitroso-redox imbalance. The observations raise the possibility of exploiting the nitrosylation susceptibility of TrxR1 for killing tumor cells. PMID- 27377781 TI - Equity in access to health care in a rural population in Malaysia: A cross sectional study. AB - OBJECTIVE: To examine the extent of equity in access to health care, their determinants and reasons of unmet need of a rural population in Malaysia. DESIGN: Exploratory cross-sectional survey administered by trained interviewers among participants of a health screening program. SETTING: A rural plantation estate in the West Coast of Peninsular Malaysia. PARTICIPANTS: One hundred and thirty out of 142 adults above 18 years old who attended the program. MAIN OUTCOME MEASURE: Percentages of respondents reporting realised access and unmet need to health care, determinants of both access indicators and reasons for unmet need. Realised access associated with need but not predisposing or enabling factors and unmet need not associated with any variables were considered equitable. RESULTS: A total of 88 (67.7%) respondents had visited a doctor (realised access) in the past 6 months and 24.8% (n = 31) experienced unmet need in the past 12 months. Using logistic regression, realised access was associated with presence of chronic disease (OR 6.97, P < 0.001), whereas unmet need was associated with low education level (OR 6.50, P < 0.05), 'poor' or 'fair' self-assessed health status (OR 6.03, P < 0.05) and highest income group (> RM 2000 per month) (OR 51.27, P < 0.05). Personal choice (67.7%) was more commonly expressed than barriers (54.8%) as reasons for unmet need. CONCLUSIONS: The study found equity in realised access and inequity in unmet need among the rural population, the latter associated with education level, subjective health status and income. Despite not being generalisable, the findings highlight the need for a national level study on equity in access before the country reforms its health system. PMID- 27377782 TI - Effect of abdominal bracing training on strength and power of trunk and lower limb muscles. AB - PURPOSE: It is unknown whether maximal voluntary co-contraction of abdominal muscles, called abdominal bracing, can be a training maneuver for improving strength and power of trunk and lower limb muscles. The present study aimed to elucidate this. METHODS: Twenty young adult men (23.3 +/- 1.8 years) were allocated to training (TG, n = 11) or control (CG, n = 9) group. TG conducted an 8-week training program (3 days/week) consisting of 2-s maximal abdominal bracing followed by 2-s muscle relaxation (5 * 10 repetitions/day). Maximal voluntary isometric strength during trunk flexion and extension, hip extension, and knee extension, maximal lifting power from sitting position, and the thicknesses of abdominal muscles were measured before and after the intervention. In addition, surface electromyograms from trunk and lower limb muscles and intra-abdominal pressure (IAP) during the maximal abdominal bracing and maximal lifting tasks were also determined. RESULTS: After the intervention, TG showed significant increases in isometric trunk extension (+14.4 %) and hip extension (+34.7 %) strength and maximal lifting power (+15.6 %), while CG did not show any changes in strength and power variables. Furthermore, TG had significant gains in the muscle thickness of the oblique internal (+22.4 %), maximal IAP during abdominal bracing (+36.8 %), and the rate of IAP rise during lifting task (+58.8 %), without corresponding changes in CG. CONCLUSION: The current study indicates that a training style with maximal voluntary co-contraction of abdominal muscles can be an effective maneuver for increasing strength and power during movements involving trunk and hip extensions, without using external load. PMID- 27377783 TI - Reusable, extensible, and modifiable R scripts and Kepler workflows for comprehensive single set ChIP-seq analysis. AB - BACKGROUND: There has been an enormous expansion of use of chromatin immunoprecipitation followed by sequencing (ChIP-seq) technologies. Analysis of large-scale ChIP-seq datasets involves a complex series of steps and production of several specialized graphical outputs. A number of systems have emphasized custom development of ChIP-seq pipelines. These systems are primarily based on custom programming of a single, complex pipeline or supply libraries of modules and do not produce the full range of outputs commonly produced for ChIP-seq datasets. It is desirable to have more comprehensive pipelines, in particular ones addressing common metadata tasks, such as pathway analysis, and pipelines producing standard complex graphical outputs. It is advantageous if these are highly modular systems, available as both turnkey pipelines and individual modules, that are easily comprehensible, modifiable and extensible to allow rapid alteration in response to new analysis developments in this growing area. Furthermore, it is advantageous if these pipelines allow data provenance tracking. RESULTS: We present a set of 20 ChIP-seq analysis software modules implemented in the Kepler workflow system; most (18/20) were also implemented as standalone, fully functional R scripts. The set consists of four full turnkey pipelines and 16 component modules. The turnkey pipelines in Kepler allow data provenance tracking. Implementation emphasized use of common R packages and widely-used external tools (e.g., MACS for peak finding), along with custom programming. This software presents comprehensive solutions and easily repurposed code blocks for ChIP-seq analysis and pipeline creation. Tasks include mapping raw reads, peakfinding via MACS, summary statistics, peak location statistics, summary plots centered on the transcription start site (TSS), gene ontology, pathway analysis, and de novo motif finding, among others. CONCLUSIONS: These pipelines range from those performing a single task to those performing full analyses of ChIP-seq data. The pipelines are supplied as both Kepler workflows, which allow data provenance tracking, and, in the majority of cases, as standalone R scripts. These pipelines are designed for ease of modification and repurposing. PMID- 27377784 TI - Re: Scientific basis for standardization of fetal head measurements by ultrasound: a reproducibility study. R. Napolitano, V. Donadono, E. O. Ohuma, C. L. Knight, S. Z. Wanyonyi, B. Kemp, T. Norris and A. T. Papageorghiou. Ultrasound Obstet Gynecol 2016; 48: 80-85. PMID- 27377785 TI - Re: Angle of fetal head progression measured using transperineal ultrasound as a predictive factor of vacuum extraction failure. T. Bultez, T. Quibel, P. Bouhanna, T. Popowski, M. Resche-Rigon and P. Rozenberg. Ultrasound Obstet Gynecol 2016; 48: 86-91. PMID- 27377786 TI - Reply. PMID- 27377787 TI - Re: Accuracy of first-trimester ultrasound in diagnosis of tubal ectopic pregnancy in the absence of an obvious extrauterine embryo: systematic review and meta-analysis. PMID- 27377788 TI - Neural correlates of mindful self-awareness in mindfulness meditators and meditation-naive subjects revisited. AB - Mindful self-awareness is central to mindfulness meditation and plays a key role in its salutary effects. It has been related to decreased activation in cortical midline structures (CMS) and amygdala, and increased activation in somatosensory regions. However, findings in untrained individuals are contradictory, and scarce in experienced meditators. Using fMRI, we investigated experienced mindfulness meditators (LTM, n=21, average 4652 practice-hours) and matched meditation-naive participants (MNP, n=19) during short periods of mindful self-awareness (FEEL) and self-referential thinking (THINK). We report somatosensory activations and decreases in CMS during FEEL for both groups, but significantly stronger decreases in prefrontal CMS in LTM. LTM further showed decreases in language related and amygdala regions, but the latter was not significantly different between groups. Overall, higher activations in amygdala and mid-line regions during FEEL were related to levels of depressiveness. Neural patterns of mindful self-awareness emerge already in MNP but more pronounced in LTM. Specifically, meditation training might reduce self-reference and verbalization during mindful awareness. We further corroborate the suggested link between mindfulness and healthy self-related functions on the neural level. Longitudinal studies need to corroborate these findings. PMID- 27377789 TI - Distinguishing shyness and sociability in adults: An event-related electrocortical-neuroendocrine study. AB - Shyness and sociability are orthogonal personality dimensions, but little is known about how the two traits are instantiated in the brain and body. Using a 3 stimulus auditory oddball task, we examined whether shyness and sociability were distinguishable on P300 event-related potentials (ERPs) in processing task relevant, novel, and standard auditory tones in 48 young adults. ERP amplitudes were measured at four midline scalp sites (Fz, FCz, Cz, Pz). We found that shyness, but not sociability, was related to reduced frontal novelty P300 amplitudes and to high emotionality. We also found that low baseline salivary cortisol levels mediated the relation between: (a) high shyness and reduced frontal P300 amplitudes to novel tones, and (b) high shyness and high scores of emotionality. We speculate that low baseline cortisol may serve as a putative mechanism influencing central attentional states of avoidance to threat and novelty and emotional arousal in adults who are shy. PMID- 27377790 TI - Investigating the behavioural effects of a mobile-phone based home telehealth intervention in people with insulin-requiring diabetes: Results of a randomized controlled trial with patient interviews. AB - Introduction Evidence supporting home telehealth effects on clinical outcomes in diabetes is available, yet mechanisms of action for these improvements remain poorly understood. Behavioural change is one plausible explanation. This study investigated the behavioural effects of a mobile-phone based home telehealth (MTH) intervention in people with diabetes. It was hypothesized that MTH would improve self-efficacy, illness beliefs, and diabetes self-care. Methods A randomized controlled trial compared standard care to standard care supplemented with MTH (self-monitoring, data transmission, graphical and nurse-initiated feedback, educational calls). Self-report measures of self-efficacy, illness beliefs, and self-care were repeated at baseline, three months, and nine months. MTH effects were based on the group by time interactions in hierarchical linear models and effect sizes with 95% confidence intervals (CIs). Interviews with MTH participants explored the perceived effects of MTH on diabetes self-management. Results Eighty-one participants were randomized to the intervention ( n = 45) and standard care ( n = 36). Significant group by time effects were observed for five out of seven self-efficacy subscales. Effect sizes were large, particularly at nine months. Interaction effects for illness beliefs and self-care were non significant, but effect sizes and confidence intervals suggested MTH may positively affect diet and exercise. In interviews, MTH was associated with increased awareness, motivation, and a greater sense of security. Improved self monitoring and diet were reported by some participants. Discussion MTH empowers people with diabetes to manage their condition and may influence self-care. Future MTH research would benefit from investigating behavioural mechanisms and determining patient profiles predictive of greater behavioural effectiveness. PMID- 27377791 TI - An asynchronous telemedicine program: Three years' experience with African patients treated in Spain. PMID- 27377792 TI - Technology-enhanced suicide prevention interventions: A systematic review. AB - Objective Suicide prevention is a high priority. Scalable and sustainable interventions for suicide prevention are needed to set the stage for population level impact. This systematic review explores how technology-enhanced interventions target suicide risk and protective factors, using the Centers for Disease Control and Prevention (CDC, 2015) Risk and Protective Factors Ecological Model. Methods Information databases (PsycINFO, PubMed and CINAHL) were systematically searched and records including technology-enhanced interventions for suicide prevention ( n = 3764) were reviewed. Records with varying technologies and diverse methodologies were integrated into the search. Results Review of the records resulted in the inclusion of 16 studies that utilized technology-enhanced interventions to address determinants of suicidal behaviour. This includes the use of standalone or, in most cases, adjunct technology enhanced interventions for suicide prevention delivered by mobile phone application, text message, telephone, computer, web, CD-ROM and video. Conclusion Intervention effectiveness was variable, but several technology-enhanced interventions have demonstrated effectiveness in reducing suicidal ideation and mental health co-morbidities. Large-scale research and evaluation initiatives are needed to evaluate the costs and long-term population-level impact of these interventions. PMID- 27377793 TI - The effectiveness of risk assessment methods: Commentary on "Deciding on child maltreatment: A literature review on methods that improve decision-making". PMID- 27377795 TI - Early prediction of maxillary canine impaction: number doubts: Author response. PMID- 27377796 TI - First Isolation and Characterization of the Highly Coordinated Group 14 Enolates: Effects of the Coordination Controls on the Geometry and Tautomerization of Germyl Enolates. AB - The Group 14 enolates play an important part in many organic reactions. Herein, the reduction of an alpha-bromo ketone with germanium(II) salts cleanly afforded the corresponding germyl enolate as an isolatable species. This experimental reductive generation of a germyl enolate enabled us to characterize both C- and O bound tautomers derived from an identical precursor and to unveil the tautomeric mechanisms, including the kinetic parameters and the relative stability of these tautomers, along with confirmation from DFT calculations. Moreover, the highly coordinated germyl enolates were isolated by a stabilization process induced by adding ligands. All products were characterized by NMR spectroscopy and X-ray crystallography. PMID- 27377794 TI - The pan-Kv7 (KCNQ) Channel Opener Retigabine Inhibits Striatal Excitability by Direct Action on Striatal Neurons In Vivo. AB - Central Kv7 (KCNQ) channels are voltage-dependent potassium channels composed of different combinations of four Kv7 subunits, being differently expressed in the brain. Notably, striatal dopaminergic neurotransmission is strongly suppressed by systemic administration of the pan-Kv7 channel opener retigabine. The effect of retigabine likely involves the inhibition of the activity in mesencephalic dopaminergic neurons projecting to the striatum, but whether Kv7 channels expressed in the striatum may also play a role is not resolved. We therefore assessed the effect of intrastriatal retigabine administration on striatal neuronal excitability in the rat determined by c-Fos immunoreactivity, a marker of neuronal activation. When retigabine was applied locally in the striatum, this resulted in a marked reduction in the number of c-Fos-positive neurons after a strong excitatory striatal stimulus induced by acute systemic haloperidol administration in the rat. The relative mRNA levels of Kv7 subunits in the rat striatum were found to be Kv7.2 = Kv7.3 = Kv7.5 > >Kv7.4. These data suggest that intrastriatal Kv7 channels play a direct role in regulating striatal excitability in vivo. PMID- 27377797 TI - A rapid and simple method for the determination of psychoactive alkaloids by CE UV: application to Peganum Harmala seed infusions. AB - The beta-carboline alkaloids of the harmala (HAlks) group are compounds widely spread in many natural sources, but found at relatively high levels in some specific plants like Peganum harmala (Syrian rue) or Banisteriopsis caapi. HAlks are a reversible Mono Amino Oxidase type A Inhibitor (MAOI) and, as a consequence, these plants or their extracts can be used to produce psychotropic effects when are combined with psychotropic drugs based on amino groups. Since the occurrence and the levels of the HAlks in natural sources are subject to significant variability, more widespread use is not clinical but recreational or ritual, for example B. caapi is a known part of the Ayahuasca ritual mixture. The lack of simple methods to control the variable levels of these compounds in natural sources restricts the possibilities to dose in strict quantities and, as a consequence, limits its use with pharmacological or clinical purposes. In this work, we present a fast, simple, and robust method of quantifying simultaneously the six HAlks more frequently found in plants, i.e., harmine, harmaline, harmol, harmalol, harmane, and norharmane, by capillary electrophoresis instruments equipped with the more common detector UV. The method is applied to analyze these HAlks in P. Harmala seeds infusion which is a frequent intake form for these HAlks. The method is validated in three different instruments in order to evaluate the transferability and to compare the performances between them. In this case, harmaline, harmine, and harmol were found in the infusion samples. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27377798 TI - The effect of 3-ketosteroid-Delta(1)-dehydrogenase isoenzymes on the transformation of AD to 9alpha-OH-AD by Rhodococcus rhodochrous DSM43269. AB - Rhodococcus rhodochrous DSM43269 is well known for its 3-ketosteroid-9alpha hydroxylases. However, the function of its 3-ketosteroid-Delta(1)-dehydrogenases (KSDD) remains unknown. This study compared the involvement of ksdds in the strain's androst-4-ene-3,17-dione (AD) transformation via gene deletion. The conversion was performed using AD as substrate or directly with 9alpha hydroxyandrost-4-ene-3,17-dione (9alpha-OH-AD). The single deletion of ksdd1 or ksdd3 did not appear to result in the accumulation of 9alpha-OH-AD, whereas the single mutant ?ksdd2 could preserve this compound to some extent. To further compare the role of ksdds in this strain, double mutants were constructed. All ksdd2 mutants combined with ksdd1 and/or ksdd3 resulted in the accumulation of 9alpha-OH-AD, among which the double mutant ?ksdd2,3 behaved similarly to the single mutant ?ksdd2 in this process. The mutant that lacked both ksdd1 and ksdd3 was still displayed, with no effect on the degradation of 9alpha-OH-AD. The triple mutant ?ksdd1,2,3 was then constructed and exhibited the same capability as ?ksdd1,2, accumulating more 9alpha-OH-AD than ?ksdd2,3 and ?ksdd2. The transcription of KSDD1 and KSDD2 increased, whereas that of KSDD3 seemed to exhibit no change, despite the use of the inducer AD or 9alpha-OH-AD. Thus, only ksdd1 and ksdd2 were involved in the transformation of AD to 9alpha-OH-AD. ksdd2 had the main role, ksdd1 had a minor effect on 9alpha-OH-AD degradation, and ksdd3 did not exhibit any action in this course. PMID- 27377799 TI - A method for simultaneous gene overexpression and inactivation in the Corynebacterium glutamicum genome. AB - The gene integration method is an important tool to stably express desirable genes in bacteria. To avoid heavy workload and cost, we constructed a rapid and efficient method for genome modification. This method depended on a mobilizable plasmid, which contains a P tac promoter, an introduced multiple cloning site (iMCS), and rrnBT1T2 terminator. Briefly, the mobilizable plasmid pK18-MBPMT with the P tac-iMCS-rrnBT1T2 cartridge derived from pK18mobsacB was prepared to directly integrate hetero-/homologous DNA into the Corynebacterium glutamicum genome. Like our previous method, this method was based on insertional inactivation and double-crossover homologous recombination, which simultaneously achieved gene overexpression and inactivation in the genome without the use of genetic markers. Compared to the previous method, this protocol omitted the construction of a recombinant expression plasmid and clone of the target gene(s) cassette, which significantly decreased the workload, cost, and operational time. Using this method, the heterologous gene amy and the homologous gene lysC (T311I) were successfully integrated into the C. glutamicum genome at alaT and avtA loci, respectively. Moreover, the operation time of this method was shorter than that of the previous method, especially for repeated integration. This method, which is based on the mobilizable plasmid pK18-MBPMT, thus represents a potentially attractive protocol for the integration of genes in the course of genetic modification of C. glutamicum. PMID- 27377800 TI - A broken heart in a broken car. AB - Takotsubo syndrome (TTS) is still a relatively understudied and often undetected disease. It is usually preceded by emotional or physical triggers. We here report a case of TTS following a car accident. Typical apical ballooning with moderate reduction of left ventricular ejection fraction (LVEF) and increased level of pro B-type natriuretic peptide (BNP) as well as slightly increased creatine kinase and troponin T values were found in this 76-year-old female patient, 6 h after a car accident. At 10 weeks follow-up, we observed a normalization of regional wall motion, LVEF, electrocardiogram and pro-BNP. TTS is an acute heart failure syndrome and an important differential diagnosis of acute coronary syndrome. PMID- 27377801 TI - Commentary to the article "Metabolic syndrome is associated with different clinical outcome after cardiac resynchronization therapy in patients with ischemic and non-ischemic cardiomyopathy". PMID- 27377802 TI - Response to the letter regarding article "Metabolic syndrome is associated with different clinical outcome after cardiac resynchronization therapy in patients with ischemic and non-ischemic cardiomyopathy". PMID- 27377803 TI - Whole blood cell parameters help us predict the prognosis in patients with acute ST segment elevation myocardial infarction: Myth or reality? PMID- 27377804 TI - White blood cell count to mean platelet volume ratio as a novel blood cell parameter. Authors' reply. PMID- 27377805 TI - Pericardial effusion can affect the Tp-e interval and Tp-e/QT ratio. PMID- 27377806 TI - Pericardial effusion: The key point is the underlying etiology. Authors' reply. PMID- 27377807 TI - Inflammatory parameters must always be taken into account in ST-segment elevation myocardial infarction. PMID- 27377808 TI - Response to the comments to the article "Does SYNTAX score II predict poor myocardial perfusion in ST-segment elevation myocardial infarction?". PMID- 27377809 TI - Utilization of public oral health services by New South Wales teenagers, 2004-05 to 2014-15. AB - BACKGROUND: The aims of this study were to examine variations in levels of access to public oral health services in New South Wales by teenagers from 2004-05 to 2014-15 and to determine whether more teenagers have been treated with preventive dental items in keeping with the strategic shift statewide towards prevention and early intervention. METHODS: This study involved an analysis of a subset of the New South Wales Oral Health Data Collection for teenagers treated in the New South Wales Public Oral Health Service in the financial years 2004-05 to 2014-15. Relevant Australian Dental Association dental service item groups are reported for teenagers by year as a percentage of total visits delivered in that year. RESULTS: The utilization of the New South Wales Public Oral Health Service by teenagers has remained relatively stable over the 11 years at approximately 6%, while the provision of some preventive items increased over the time period. CONCLUSIONS: There were important differences found in access by teenagers to preventive items by socio-economic status and rurality, and these differences will be targeted over the coming years by New South Wales Public Oral Health Services and better monitored by a new electronic oral health record being implemented statewide from 2016. PMID- 27377810 TI - Ulceration in bladder cancer associates with extravesical disease, independent of cell cycle, or hypoxia pathways status: Integrating gross morphology and expression profiles in cystectomies. AB - OBJECTIVE: Ulceration is common in bladder tumors, but its prognostic role, although intuitive, is not established. We aim to explore the presence of gross ulceration and its relationship with other morphological and biological features classically associated with extravesical disease, in patients submitted to radical cystectomy. METHODS: Tumor size and morphology were noted on 101 cystectomy patients (2000-2010). Papillary, exophytic, and vegetant tumors were grouped as "papillary" and solid/nodular, ulcerated and infiltrative as "nonpapillary." Ulceration was noted grossly in every case as a binary parameter, regardless of morphology. Immunohistochemistry was performed for hypoxia (hypoxia inducible factor-1alpha and vascular endothelial growth factor), and cell cycle proteins (pRb, p53, and cyclin D1). RESULTS: Mean age was 66.7 year, male:female ratio was 2:1, 20 patients received bacillus Calmette-Guerin and 10 neoadjuvant chemotherapy. Upstaging rate was 56.4%. Ulcerated lesions presented mostly as nonpapillary and nonorgan confined (nOC), whereas nonulcerated tumors were often papillary and organ confined (OC). Tumor size was smaller in nonpapillary tumors (P = 0.002), but did not associate with altered hypoxia or cell cycle expressions. pRb and cyclin D1 loss and p53 overexpression were more frequent in ulcerated and non-OC tumors as did the phenotype vascular endothelial growth factor-negative/hypoxia-inducible factor-1alpha-low (P<0.001). On a multivariate model, ulceration was an independent predictor of non-OC and extravesical disease. CONCLUSION: Patients with ulcerated tumors were often staged with extravesical disease, independent of other morphologic and biological features known to affect prognosis. Prospective studies are needed to confirm the predictive value of tumor ulceration at cystoscopy, which could improve patient stratification for neoadjuvant chemotherapy. PMID- 27377811 TI - Enantioselective Total Synthesis of RQN-18690A (18-Deoxyherboxidiene). AB - The first total synthesis of RQN-18690A (18-deoxyherboxidiene) and the determination of its absolute stereochemical configuration are described. The synthesis features an organocatalytic aldol reaction for the first step, 1,4- and 1,2- dual reductions of alpha,beta-unsaturated delta-lactone followed by a domino reaction in a one-pot operation, and diastereoselective epoxidation with kinetic resolution. PMID- 27377813 TI - The Potent Inhibitory Effect of a Naproxen-Appended Cobalt(III)-Cyclam Complex on Cancer Stem Cells. AB - We report the potency against cancer stem cells (CSCs) of a new cobalt(III) cyclam complex (1) that bears the nonsteroidal anti-inflammatory drug, naproxen. The complex displays selective potency for breast CSC-enriched HMLER-shEcad cells over breast CSC-depleted HMLER cells. Additionally, it inhibited the formation of three-dimensional tumour-like mammospheres, and reduced their viability to a greater extent than clinically used breast cancer drugs (vinorelbine, cisplatin and paclitaxel). The anti-mammosphere potency of 1 was enhanced under hypoxia mimicking conditions. Detailed mechanistic studies revealed that DNA damage and cyclooxygenase-2 (COX-2) inhibition contribute to the cytotoxic mechanism of 1. To the best of our knowledge, 1 is the first cobalt-containing compound to show selective potency for CSCs over bulk cancer cells. PMID- 27377812 TI - IGFBP-3 inhibits Wnt signaling in metastatic melanoma cells. AB - In previous works, we have shown that insulin-like growth factor-binding protein 3 (IGFBP-3), a tissue and circulating protein able to bind to IGFs, decreases drastically in the blood serum of patients with diffuse metastatic melanoma. In agreement with the clinical data, recombinant IGFBP-3 was found to inhibit the motility and invasiveness of cultured metastatic melanoma cells and to prevent growth of grafted melanomas in mice. The present work was aimed at identifying the signal transduction pathways underlying the anti-tumoral effects of IGFBP-3. We show that the anti-tumoral effect of IGFBP-3 is due to inhibition of the Wnt pathway and depends upon the presence of CD44, a receptor protein known to modulate Wnt signaling. Once it has entered the cell, IGFBP-3 binds the Wnt signalosome interacting specifically with its component GSK-3beta. As a consequence, the beta-catenin destruction complex dissociates from the LRP6 Wnt receptor and GSK-3beta is activated through dephosphorylation, becoming free to target cytoplasmic beta-catenin which is degraded by the proteasomal pathway. Altogether, the results suggest that IGFBP-3 is a novel and effective inhibitor of Wnt signaling. As IGFBP-3 is a physiological protein which has no detectable toxic effects either on cultured cells or live mice, it might qualify as an interesting new therapeutic agent in melanoma, and potentially many other cancers with a hyperactive Wnt signaling. (c) 2016 The Authors. Molecular Carcinogenesis Published by Wiley Periodicals, Inc. PMID- 27377814 TI - Correction: Near infrared activation of an anticancer Pt(IV) complex by Tm-doped upconversion nanoparticles. AB - Correction for 'Near infrared activation of an anticancer Pt(IV) complex by Tm doped upconversion nanoparticles' by Emmanuel Ruggiero et al., Chem. Commun., 2015, 51, 2091-2094. PMID- 27377815 TI - EULAR revised recommendations for the management of fibromyalgia. AB - OBJECTIVE: The original European League Against Rheumatism recommendations for managing fibromyalgia assessed evidence up to 2005. The paucity of studies meant that most recommendations were 'expert opinion'. METHODS: A multidisciplinary group from 12 countries assessed evidence with a focus on systematic reviews and meta-analyses concerned with pharmacological/non-pharmacological management for fibromyalgia. A review, in May 2015, identified eligible publications and key outcomes assessed were pain, fatigue, sleep and daily functioning. The Grading of Recommendations Assessment, Development and Evaluation system was used for making recommendations. RESULTS: 2979 titles were identified: from these 275 full papers were selected for review and 107 reviews (and/or meta-analyses) evaluated as eligible. Based on meta-analyses, the only 'strong for' therapy-based recommendation in the guidelines was exercise. Based on expert opinion, a graduated approach, the following four main stages are suggested underpinned by shared decision-making with patients. Initial management should involve patient education and focus on non-pharmacological therapies. In case of non-response, further therapies (all of which were evaluated as 'weak for' based on meta analyses) should be tailored to the specific needs of the individual and may involve psychological therapies (for mood disorders and unhelpful coping strategies), pharmacotherapy (for severe pain or sleep disturbance) and/or a multimodal rehabilitation programme (for severe disability). CONCLUSIONS: These recommendations are underpinned by high-quality reviews and meta-analyses. The size of effect for most treatments is relatively modest. We propose research priorities clarifying who will benefit from specific interventions, their effect in combination and organisation of healthcare systems to optimise outcome. PMID- 27377816 TI - Forced exercise-induced osteoarthritis is attenuated in mice lacking the small leucine-rich proteoglycan decorin. AB - OBJECTIVE: Interterritorial regions of articular cartilage matrix are rich in decorin, a small leucine-rich proteoglycan and important structural protein, also involved in many signalling events. Decorin sequesters transforming growth factor beta (TGFbeta), thereby regulating its activity. Here, we analysed whether increased bioavailability of TGFbeta in decorin-deficient (Dcn-/-) cartilage leads to changes in biomechanical properties and resistance to osteoarthritis (OA). METHODS: Unchallenged knee cartilage was analysed by atomic force microscopy (AFM) and immunohistochemistry. Active transforming growth factor beta 1 (TGFbeta1) content within cultured chondrocyte supernatants was measured by ELISA. Quantitative real-time (RT)-PCR was used to analyse mRNA expression of glycosaminoglycan (GAG)-modifying enzymes in C28/I2 cells following TGFbeta1 treatment. In addition, OA was induced in Dcn-/- and wild-type (WT) mice via forced exercise on a treadmill. RESULTS: AFM analysis revealed a strikingly higher compressive stiffness in Dcn-/- than in WT cartilage. This was accompanied by increased negative charge and enhanced sulfation of GAG chains, but not by alterations in the levels of collagens or proteoglycan core proteins. In addition, decorin-deficient chondrocytes were shown to release more active TGFbeta1. Increased TGFbeta signalling led to enhanced Chst11 sulfotransferase expression inducing an increased negative charge density of cartilage matrix. These negative charges might attract more water resulting in augmented compressive stiffness of the tissue. Therefore, decorin-deficient mice developed significantly less OA after forced exercise than WT mice. CONCLUSIONS: Our study demonstrates that the disruption of decorin-restricted TGFbeta signalling leads to higher stiffness of articular cartilage matrix, rendering joints more resistant to OA. Therefore, the loss of an important structural component can improve cartilage homeostasis. PMID- 27377817 TI - Oxygen saturation/minute heart rate index: Simple lung function test for children. AB - BACKGROUND: The severity of airway obstruction can be accurately determined on spirometry in children with asthma. Other assessments may include peak expiratory flow and pulse oximetry. In the present study, we evaluated the validity and reliability of oxygen saturation/minute heart rate (SpO2 /MHR) index in the prediction of degree of severe airway obstruction in children with asthma. METHODS: This was a retrospective study of children aged 7-17 followed for asthma at Mersin Women and Children's Hospital. The study compared SpO2 /MHR ratio with forced expiratory volume in 1 s (FEV1 ) measured on spirometry, an important indicator of small airway obstruction. A total of 296 patients were included in the study, and classified either as having normal FEV1 (FEV1 > 80% of predicted, n = 178) or severely reduced FEV1 (FEV1 < 60% of predicted, n = 118). Positive and negative predictive values (PPV and NPV), sensitivity and specificity of SpO2 /MHR index in predicting low FEV1 were calculated on receiver operating characteristics analysis. RESULTS: An SpO2 /MHR ratio cut-off <0.90 was associated with a PPV of 83.14%, NPV of 71.77%, sensitivity of 80.34% and specificity of 75.42% in predicting low FEV1 . CONCLUSIONS: SpO2 /MHR ratio appears to be a highly useful index to assess airway obstruction in older children with asthma. Thus, it can be used as a marker of airway obstruction severity when spirometry is not available. PMID- 27377818 TI - Effects of CYP2C9 genetic polymorphisms on the pharmacokinetics of zafirlukast. AB - Zafirlukast, a cysteinyl leukotriene receptor antagonist, is indicated for the treatment of patients with mild to moderate asthma. Zafirlukast is metabolized mainly by CYP3A4 and CYP2C9. We investigated the effects of the major CYP2C9 variant alleles in Asian populations, CYP2C9*3 and CYP2C9*13, on the pharmacokinetics of zafirlukast in healthy Korean subjects. A single 20-mg oral dose of zafirlukast was given to 23 Korean male subjects divided into two genotype groups according to CYP2C9 genotypes, CYP2C9EM (n = 11; CYP2C9*1/*1) and CYP2C9IM (n = 12; 9 and 3 carriers of CYP2C9*1/*3 and *1/*13, respectively). Zafirlukast concentrations were determined using a validated HPLC-MS/MS analytical method in plasma samples collected after the drug intake. Compared with the CYP2C9EM group, the Cmax and AUCinf of zafirlukast in the CYP2C9IM group were 1.44- and 1.70-fold higher, respectively (p < 0.01 and p < 0.0001). The CL/F of zafirlukast was 42.8 % lower in the CYP2C9IM group compared with the CYP2C9EM group (p < 0.001). Slightly higher Cmax and AUC, and lower CL/F of zafirlukast were observed in subjects with the CYP2C9*1/*13 genotype compared with the CYP2C9*1/*3 genotype subjects. CYP2C9*3 and CYP2C9*13 alleles significantly affected the plasma concentrations of zafirlukast. PMID- 27377820 TI - Respiratory sinus arrhythmia reactivity of internet addiction abusers in negative and positive emotional states using film clips stimulation. AB - BACKGROUND AND AIMS: People with internet addiction (IA) suffer from mental, physical, social, and occupational problems. IA includes psychological and physiological syndromes, and among the syndromes, emotion was suggested important mental and physiological expressions of IA. However, few physiologically emotional characters of IA were investigated. Autonomic nervous system (ANS) activity was a good link between IA and emotion, and respiratory sinus arrhythmia (RSA) gained from ANS was hypothesized related to IA. METHODS: An emotional induction experiment using negative and positive emotional films was conducted to validate the hypotheses. Thirty-four participants recruited from college were classified into high-risk IA group (HIA) and low-risk IA group (LIA). The respiratory signals, ECG signals, and self-assessed emotional intensity were acquired. The relationship and difference between IA and RSA was tested using descriptive statistics and inferential statistics. RESULTS: The RSA values of HIA were lower than those of LIA both before and after the induction of positive and negative emotions. When participants experienced a negative emotion (anger or fear), their RSA values declined; the decline for HIA was greater than that for LIA. The RSA values of HIA participants before induction of fear, happiness, or surprise, statistically significantly differed from that after induction of those emotions, with p values of 0.007, 0.04 and 0.01 respectively. The difference between the changes in RSA values upon the induction of surprise of HIA and LIA was statistically significant difference (p = 0.03). The interaction between two IA groups among emotional induction states was statistically significant difference. CONCLUSIONS: RSA value here was the main variable that reflected ANS activity, and especially vagus nerve regulation. The results revealed that the changes in RSA values were biologically significantly different between HIA and LIA, especially when sadness, happiness, or surprise was induced. HIA people exhibited stronger RSA reactivity following negative emotion than LIA people, but the RSA reactivity following positive emotion was weaker. This study provides more physiological information about IA and assists further investigation on the regulation of the ANS for IA abusers. The results will benefit the further application, early detection, therapy, and even early prevention. Clinical trial registration details This study was approved by the Institution Review Board of the National Taiwan University Hospital, Hsinchu Branch (Hsinchu, Taiwan), under the research project: A study of interactions between cognition, emotion and physiology (contract no.100IRB-32). PMID- 27377819 TI - Azacytidine mitigates experimental sclerodermic chronic graft-versus-host disease. AB - BACKGROUND: Previous studies have demonstrated that regulatory T cells (Tregs) play a protective role in the pathogenesis of chronic graft-versus-host disease (cGVHD). Tregs constitutively express the gene of the transcription factor Foxp3 whose CNS2 region is heavily methylated in conventional CD4(+) T cells (CD4(+)Tconvs) but demethylated in Tregs. METHODS: Here, we assessed the impact of azacytidine (AZA) on cGVHD in a well-established murine model of sclerodermic cGVHD (B10.D2 (H-2d) -> BALB/cJ (H-2d)). RESULTS: The administration of AZA every 48 h from day +10 to day +30 at the dose of 0.5 mg/kg or 2 mg/kg mitigated chronic GVHD. Further, AZA-treated mice exhibited higher blood and thymic Treg frequencies on day +35, as well as higher demethylation levels of the Foxp3 enhancer and the IL-2 promoter in splenocytes at day +52. Interestingly, Tregs from AZA-treated mice expressed more frequently the activation marker CD103 on day +52. AZA-treated mice had also lower counts of CD4(+)Tconvs and CD8(+) T cells from day +21 to day +35 after transplantation, as well as a lower proportion of CD4(+)Tconvs expressing the Ki67 antigen on day +21 demonstrating an anti-proliferating effect of the drug on T cells. CONCLUSIONS: Our results indicate that AZA prevented sclerodermic cGVHD in a well-established murine model of cGVHD. These data might serve as the basis for a pilot study of AZA administration for cGVHD prevention in patients at high risk for cGVHD. PMID- 27377822 TI - Bipolar switching in chalcogenide phase change memory. AB - Phase change materials based on chalcogenides are key enabling technologies for optical storage, such as rewritable CD and DVD, and recently also electrical nonvolatile memory, named phase change memory (PCM). In a PCM, the amorphous or crystalline phase affects the material band structure, hence the device resistance. Although phase transformation is extremely fast and repeatable, the amorphous phase suffers structural relaxation and crystallization at relatively low temperatures, which may affect the temperature stability of PCM state. To improve the time/temperature stability of the PCM, novel operation modes of the device should be identified. Here, we present bipolar switching operation of PCM, which is interpreted by ion migration in the solid state induced by elevated temperature and electric field similar to the bipolar switching in metal oxides. The temperature stability of the high resistance state is demonstrated and explained based on the local depletion of chemical species from the electrode region. PMID- 27377821 TI - Relationship between nongenital tender point tenderness and intravaginal muscle pain intensity: ratings in women with provoked vestibulodynia and implications for treatment. AB - BACKGROUND: Vulvodynia is a chronic vulvar pain disorder and fibromyalgia is a chronic widespread musculoskeletal pain disorder, both of unknown etiology. Association of these conditions is well documented. Intravaginal algometer measurement of tenderness to pressure applied to the pelvic floor muscles helps define vulvodynia associated with musculoskeletal factors. Women with both vulvodynia and fibromyalgia might have increased pelvic muscle pain compared to women with vulvodynia alone, defining the possible link of these 2 conditions. OBJECTIVE: We sought to: (1) correlate pain intensity during the nongenital tender point tenderness examination to pain intensity with the vaginal algometer in women with provoked vestibulodynia, and (2) determine whether subjects with provoked vestibulodynia and fibromyalgia had higher pain intensity scores with the vaginal algometer than those without fibromyalgia. STUDY DESIGN: In all, 92 subjects referred for vulvar pain were confirmed to have provoked vestibulodynia using the cotton swab test. A diagnosis of fibromyalgia was made if pain was present (numeric rating scale >1) in at least 11 sites of the 18-point nongenital tender point tenderness exam. Vaginal pain sensitivity was measured using an intravaginal pressure algometer, where 0.1, 0.3, and 0.5 kg/cm2 forces were applied digitally in random assignment by force and location to the right and left iliococcygeus muscle regions and the posterior vaginal wall. Both tender point tenderness and algometer pain intensity were reported on a 0 (no pain) to 10 (worse pain) numeric rating scale. Correlations were computed between the composite pain intensity (total of rating scale from each pressure threshold at specified site) of nongenital and those of iliococcygeus regions and the posterior vaginal wall. Independent t tests were used to determine differences in iliococcygeus regions and the posterior vaginal algometer pain ratings and presence or absence of fibromyalgia. The significance level was at P < .05. The data were expressed as mean +/- SD. RESULTS: A significant correlation was found between numeric rating scale pain scores on the nongenital tender point tenderness exam and algometer testing on the iliococcygeus region (r = 0.44, P < .0001) and the posterior vaginal wall (r = 0.45, P < .0001). Subjects with fibromyalgia by tender point tenderness had significantly higher iliococcygeal pain (6.14 +/- 2.07 vs 3.74 +/- 2.22, P = .0001) and posterior vaginal wall pain (5.67 +/- 2.10 vs 3.07 +/- 2.16, P < .0001) than women without fibromyalgia by tender point tenderness. CONCLUSION: Women with provoked vestibulodynia who experience more severe pain with nongenital tender point palpation also experience more deep vaginal pain on pelvic exam. Those who fulfill the diagnosis of fibromyalgia show significantly more intense deep vaginal pain to palpation of iliococcygeus muscles and posterior vaginal wall. Further research using a more precise definition of fibromyalgia is necessary to confirm this relationship, but findings suggest that women with provoked vestibulodynia coexisting with fibromyalgia have greater risk of superimposed vaginal muscle pain and may be candidates for early adjunctive pelvic floor physical therapy. These findings need to be explored in women with generalized, nonprovoked vulvodynia. PMID- 27377823 TI - Genetic variation and the D2 dopamine receptor: implications for the treatment of neuropsychiatric disease. PMID- 27377824 TI - Long non-coding RNA expression profiling in the NCI60 cancer cell line panel using high-throughput RT-qPCR. AB - Long non-coding RNAs (lncRNAs) form a new class of RNA molecules implicated in various aspects of protein coding gene expression regulation. To study lncRNAs in cancer, we generated expression profiles for 1707 human lncRNAs in the NCI60 cancer cell line panel using a high-throughput nanowell RT-qPCR platform. We describe how qPCR assays were designed and validated and provide processed and normalized expression data for further analysis. Data quality is demonstrated by matching the lncRNA expression profiles with phenotypic and genomic characteristics of the cancer cell lines. This data set can be integrated with publicly available omics and pharmacological data sets to uncover novel associations between lncRNA expression and mRNA expression, miRNA expression, DNA copy number, protein coding gene mutation status or drug response. PMID- 27377825 TI - The impending financial healthcare burden and ethical dilemma of systemic therapy in metastatic cancer. AB - Metastatic cancer remains a devastating disease that threatens to disrupt entire family structures creating economic and psychosocial stress. Fortunately, great strides have resulted in improved therapies over the years but at a huge social economic cost. The economic burden has risen greatly and carries with it new ethical concerns when deciding treatment. Here, we discuss the financial and ethical challenges that oncologists and their patients face in the era of novel treatment strategies. J. Surg. Oncol. 2016;114:323-328. (c) 2016 Wiley Periodicals, Inc. PMID- 27377826 TI - Web-Based Positive Psychology Interventions: A Reexamination of Effectiveness. AB - OBJECTIVE: Seligman, Steen, Park, and Peterson (2005) suggested that positive psychology interventions (PPIs) contain specific, powerful, therapeutic ingredients that effect greater increases in happiness and reductions in depression than a placebo control. This study reexamined the three PPIs that Seligman et al. found to be most effective when delivered over the internet. METHOD: Three PPIs and a placebo control, identical with the interventions used by Seligman et al., were examined in a web-based, randomized assignment design. RESULTS: Mixed-design analysis of variance and multilevel modeling showed that all interventions, including the placebo, led to significant increases in happiness and reductions in depression. The effects of PPIs were indistinguishable from those of the placebo control. CONCLUSION: Using web-based delivery, both PPIs and theoretically neutral placebos can increase happiness and reduce depression in self-selected populations. Possible explanations include that non-specific factors common to most therapeutic treatments are responsible for the observed changes, or that cultural or other context-related variables operate to account for the divergent findings. PMID- 27377827 TI - Long-term survival and BRCA status in male breast cancer: a retrospective single center analysis. AB - BACKGROUND: Male breast cancer (MBC) is rare. Given the paucity of randomized trials, treatment is generally extrapolated from female breast cancer guidelines. METHODS: This is a retrospective analysis of all male patients presenting with MBC at the Department of Oncology at University Federico II of Naples between January 1989 and January 2014. We recorded the following data: baseline characteristics (age, height, weight, body mass index, risk factors, family history), tumor characteristics (side affected, stage, histotype, hormonal and HER2 status, and Ki-67 expression), treatment (type of surgery, chemotherapy, endocrine therapy, and/or radiotherapy), BRCA1/2 mutation status (if available), other tumors, and long-term survival. RESULTS: Forty-seven patients were analyzed. Median age was 62.0 [55.0-72.0]. Among risk factors, obesity and family history of breast cancer were associated with 21 % and 30 % of MBC cases, respectively. The majority of tumors were diagnosed at an early stage: stage I (34.0 %) and stage II (44.7 %). Infiltrating ductal carcinoma was the most frequent histologic subtype (95.8 %). Hormone receptors were generally positive (88.4 % of cases were Estrogen receptor [ER] positive and 81.4 % Progesteron receptor [PgR] positive). Human epidermal growth factor receptor 2 (HER2) was positive in 26.8 % of cases; 7.0 % of MBCs were triple negative. The tumor had high proliferation index (Ki67 >= 20 %) in 64.7 %. Surgery was predominantly mastectomy (85.1 %), whereas quadrantectomy was performed in 14.9 % of patients. Adjuvant chemotherapy was administered to 70.7 % of patients, endocrine therapy to 90.2 %, trastuzumab to 16.7 % and radiotherapy to 32.6 %. BRCA status was available for 17 patients: 10 wild-type, 1 BRCA1 carrier, 5 BRCA2 carriers, 1 unknown variant sequence. The overall estimated long-term survival was about 90 % at 5 years, 80 % at 10 years and 70 % at 20 years. Patients carrying a BRCA mutation had a significantly lower survival than patients with wild-type BRCA (p = 0.04). CONCLUSIONS: Long-term survival was high in MBC patients referred to our clinical unit. Survival was poorer in BRCA-mutated patients than in patients with wild-type BRCA. PMID- 27377828 TI - French Guidelines For the Emergency Management of Headaches. PMID- 27377830 TI - Access to Intensive Care Medicine for Undocumented Migrants: The Destiny of an ECMO Center in the Middle of the Mediterranean Basin. PMID- 27377831 TI - AFM mapping of the elastic properties of brain tissue reveals kPa MUm(-1) gradients of rigidity. AB - It is now well established that the mechanical environment of the cells in tissues deeply impacts cellular fate, including life cycle, differentiation and tumor progression. Designs of biomaterials already include the control of mechanical parameters, and in general, their main focus is to control the rheological properties of the biomaterials at a macroscopic scale. However, recent studies have demonstrated that cells can stress their environment below the micron scale, and therefore could possibly respond to the rheological properties of their environment at this micron scale. In this context, probing the mechanical properties of physiological cellular environments at subcellular scales is becoming critical. To this aim, we performed in vitro indentation measurements using AFM on sliced human pituitary gland tissues. A robust methodology was implemented using elasto-adhesive models, which shows that accounting for the adhesion of the probe on the tissue is critical for the reliability of the measurement. In addition to quantifying for the first time the rigidity of normal pituitary gland tissue, with a geometric mean of 9.5 kPa, our measurements demonstrated that the mechanical properties of this tissue are far from uniform at subcellular scales. Gradients of rigidity as large as 12 kPa MUm( 1) were observed. This observation suggests that physiological rigidity can be highly non-uniform at the micron-scale. PMID- 27377833 TI - Postoperative Complications in Children With Crohn Disease Treated With Infliximab. AB - OBJECTIVES: Infliximab (IFX) has become a mainstay of therapy for children with Crohn disease (CD). Despite medical advances, many children with CD, however, still require operative interventions. The risk of complications following resection in children treated with IFX remains largely unknown. We compare surgical outcomes stratified by IFX therapy in a cohort of children with CD who require bowel resection. METHODS: We reviewed the postoperative complications in 123 children with CD who underwent bowel resection with primary anastomosis at our institution between 1977 and 2011. Demographics, medications, types of operations, and inpatient courses were analyzed. Complications and length of stay were compared based on medical therapy. RESULTS: Overall, the postoperative complication rate was 13%. Of the 123 surgical cases, 24 children had received IFX before their operation. In the children treated with IFX, we identified 3 major complications, including anastomotic leak, acute renal failure, and intraabdominal abscess. There were 9 major complications in the non-IFX group, including infections (2), intraabdominal abscesses (2), bowel obstruction, shock, supraventricular tachycardia, phlegmon, and anastomotic stricture. No significant differences in complication rates or postoperative lengths of stay were identified between those who did or did not receive IFX. CONCLUSIONS: In this cohort, surgical procedures in children and young adults treated with IFX were not associated with an increased number of complications or prolonged length of stay. Given that postoperative complications are infrequent in children, larger multicenter studies may be required to determine whether IFX therapy increases the risk of surgical complications in pediatric CD. PMID- 27377834 TI - The clinical findings in young adults with acute scrotal pain. AB - BACKGROUND: Acute scrotal pain (ASP) is a common symptom of young adults. Testicular torsion is the most important diagnosis in these cases. It is a medical emergency in which the diagnosis must be made rapidly to prevent testicular loss. This requires a high index of clinical suspicion and prompt surgical intervention. This study was conducted to examine the spectrum of diagnoses in young man with ASP in a prehospital setting, the frequency of significant diagnoses, and their outcomes. METHODS: The medical records of young adults in their obligatory military service presenting with ASP to primary care clinics from 2004 to 2014 were reviewed using the keywords: pain, testis, torsion, and orchialgia. Anamnestic data, physical findings, primary care physician decisions, and final outcomes were analyzed. RESULTS: A total of 9922 medical visits were recorded. Idiopathic scrotal pain, varicocele, scrotal trauma, and genital tract infections were the most common diagnoses. In 3 visits (0.03%), testicular cancer was diagnosed. Testicular torsion was the etiology of ASP in only 12 (0.12%) visits, and 60% the testes were salvaged. The mean duration of symptoms in the salvaged group was 6.33 hours; and in the nonsalvaged group, 44 hours. CONCLUSIONS: Testicular torsion is the etiology of ASP in only 0.12% of the visits to the primary care clinic. Patient delay before attending the primary care is responsible for most of the testes lost. Patient education in addition to high index of suspicion of primary care physicians is needed for salvage of more testicles. PMID- 27377832 TI - Heart rate response during 6-minute walking testing predicts outcome in operable chronic thromboembolic pulmonary hypertension. AB - BACKGROUND: Six-minute walk test (6MWT) is routinely performed in chronic thromboembolic pulmonary hypertension (CTEPH) before pulmonary endarterectomy (PEA). However, the clinical relevance of heart rate response (DeltaHR) and exercise-induced oxygen desaturation (EID) during 6MWT is remaining unknown. METHODS: Patients undergoing PEA in our center between 03/2013-04/2014 were assessed prospectively with hemodynamic and exercise parameters prior to and 1 year post-PEA. Patients with symptomatic chronic thromboembolic disease (mean pulmonary artery pressure (mPAP) <25 mmHg) and clinical relevant obstructive pulmonary disease were excluded. The following definitions were used: DeltaHR = (peak HR - resting HR), percent heart rate reserve (HRR) = (peak HR -rest HR)/(220 - age - rest HR) x 100 and EID = SpO2 <=88 %. RESULTS: Thirty-seven patients (of 116 patients screened) with mPAP of 43.2 +/- 8.7 mmHg, pulmonary vascular resistance (PVR) of 605.5 +/- 228.7 dyn*s/cm(5), cardiac index (CI) of 2.4 +/- 0.5 l/min/m(2) and a 6MWT-distance of 404.7 +/- 148.4 m and a peak VO2 of 12.3 +/- 3.4 ml/min/kg prior to PEA were included. Baseline DeltaHR during 6MWT was significantly associated with PVR 1 year post-PEA using linear regression analysis (r = 0.43, p = 0.01). Multivariate analysis indicated an association of HRR during 6MWT and residual PH with a hazard ratio of 1.06 (95 % Confidence interval for hazard ratio 0.99-1.14, p = 0.08). EID was observed commonly during 6MWT but no correlations to outcome parameters were found. CONCLUSIONS: This is the first prospective study to describe an association of DeltaHR during 6MWT with pulmonary hemodynamics 1 year post-PEA. Our preliminary results indicate that HRR derived from 6MWT is of clinical significance. EID was commonly observed, albeit failed as a significant prognostic factor. PMID- 27377835 TI - Hyperammonemia: clinical, therapeutic, and educational aspects. PMID- 27377836 TI - Sool's method of dislocated shoulder reduction-Cunningham technique redux? PMID- 27377837 TI - A rare cause of postpartum coma: isolated hyperammonemia due to urea cycle disorder. PMID- 27377838 TI - "Cunningham technique" dislocated shoulder reduction. PMID- 27377839 TI - Grief and loss in older people residing in nursing homes: (un)detected by nurses and care-assistants? AB - AIM: The aim of this study was to explore how nurses and care-assistants (nursing staff) working in six Flemish nursing homes experience and describe their involvement in grief care. BACKGROUND: Although grief in older people is widely described in literature, less is known about how nursing staff in nursing homes offer and perceive grief care. DESIGN: A qualitative research design with elements of constructivist grounded theory was used. METHODS: Loosely structured face-to-face interviews were done with fourteen nurses and care-assistants. Data were collected from October 2013-March 2014. Interview transcripts were analysed using the Qualitative Analysis Guide of Leuven (QUAGOL) method with support of NVivo 10. FINDINGS: Grief care in nursing homes is characterized by a complex tension between two care dimensions: (1) being involved while keeping an appropriate distance; and (2) being while doing. Nursing staff described key enablers and influencing factors for grief care at the level of both the individual and the organizational context. CONCLUSION: Findings suggest an established personal sensitivity for grief care considered from the nursing staff points of view. Nevertheless, a common denominator was the necessity to further develop a supportive and multidisciplinary grief care policy ingrained in the existing care culture. Suggested components of this grief care policy are: (a) centring attention on non-death-related loss and the cumulative nature of loss in residents; (b) building capacity by means of reflective practices; and (c) the importance of self-care strategies for nursing staff. Furthermore, the findings from this study point towards a need for education and training. PMID- 27377840 TI - Current status and future perspective of laparoscopic surgery in hepatobiliary disease. AB - Recent advances in minimally invasive surgery include laparoscopic and robotic surgery. These surgical techniques have changed the paradigm of surgical treatment for hepatobiliary diseases. Minimally invasive surgery has the advantages of minimal wound extension for cosmetic effect, early postoperative recovery, and few postoperative complications in patients. For laparoscopic liver resection, the indications have been expanded and oncological outcome was proven to be similar with open surgery in the malignant disease. Laparoscopic cholecystectomy is a classical operation for benign gallbladder diseases and the effort to decrease the surgical wound resulted to perform single incision laparoscopic cholecystectomy. For choledochal cyst, laparoscopic surgery is applied gradually despite of the difficulties associated with anastomosis, and robotic surgery for hepatobiliary disease is also performed for more minimally invasive surgery; however, while admitting the advantage of robotic surgery, robotic technology should be improved for development of more convenient and cheaper instrument and continuous efforts to enhance surgical technique to overcome long operation is necessary. In this review, the status and future perspectives of minimally invasive surgery for hepatobiliary diseases are summarized and discussed. PMID- 27377842 TI - Effect of day/night administration of three different inhalational anesthetics on melatonin levels in rats. AB - The nocturnal peak of melatonin can be altered after anesthesia and surgery. We aimed to examine the melatonin levels during the day and night after anesthesia with three commonly used inhalational anesthetics. Forty-eight male Wistar albino rats were randomized into eight groups. Rats were administered anesthesia between 7:00 am and 1:00 pm (day groups) or 7:00 pm and 1:00 am (night groups) for 6 hours. At the end of the anesthesia, blood samples were collected for assessing melatonin levels. Mean values of melatonin levels after 6 hours of anesthesia during daytime were 43.17+/-12.95 for control, 59.79+/-27.83 for isoflurane, 50.75+/-34.28 for sevoflurane and 212.20+/-49.56 pg/mL for desflurane groups. The night groups' mean melatonin levels were 136.12+/-33.20 for control, 139.85+/ 56.29 for isoflurane, 117.48+/-82.39 for sevoflurane and 128.70+/-44.63 pg/mL for desflurane groups. Desflurane anesthesia between 7:00 am and 1:00 pm significantly increased melatonin levels (p<0.001). Sevoflurane and desflurane anesthesia between 7:00 pm and 1:00 am decreased the melatonin levels but there were no significant differences (p=0.904 and p>0.99, respectively). Isoflurane anesthesia did not significantly change melatonin levels during day or night (p=0.718 and p>0.99, respectively). Our results demonstrate that during daytime desflurane anesthesia can alter melatonin levels. Altered melatonin rhythm following inhalational anesthesia can be related to sleep disorders observed after anesthesia. PMID- 27377841 TI - Effectiveness of sugammadex for cerebral ischemia/reperfusion injury. AB - Cerebral ischemia may cause permanent brain damage and behavioral dysfunction. The efficacy and mechanisms of pharmacological treatments administered immediately after cerebral damage are not fully known. Sugammadex is a licensed medication. As other cyclodextrins have not passed the necessary phase tests, trade preparations are not available, whereas sugammadex is frequently used in clinical anesthetic practice. Previous studies have not clearly described the effects of the cyclodextrin family on cerebral ischemia/reperfusion (I/R) damage. The aim of this study was to determine whether sugammadex had a neuroprotective effect against transient global cerebral ischemia. Animals were assigned to control, sham-operated, S 16 and S 100 groups. Transient global cerebral ischemia was induced by 10-minute occlusion of the bilateral common carotid artery, followed by 24-hour reperfusion. At the end of the experiment, neurological behavior scoring was performed on the rats, followed by evaluation of histomorphological and biochemical measurements. Sugammadex 16 mg/kg and 100 mg/kg improved neurological outcome, which was associated with reductions in both histological and neurological scores. The hippocampus TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) and caspase results in the S 16 and S 100 treatment groups were significantly lower than those of the I/R group. Neurological scores in the treated groups were significantly higher than those of the I/R group. The study showed that treatment with 16 mg/kg and 100 mg/kg sugammadex had a neuroprotective effect in a transient global cerebral I/R rat model. However, 100 mg/kg sugammadex was more neuroprotective in rats. PMID- 27377843 TI - Absence of CD66a expression is associated with high microvessel density and high histologic grade in hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. Patients with HCC usually have poor prognosis and high mortality. It has been shown that carcinoembryonic antigen-related cell adhesion molecule 1 (CD66a) regulates cell signaling, proliferation, and tumor growth. The aim of this study is to analyze the expression and possible role of CD66a in HCC. Immunohistochemical staining of CD66a was performed on 86 HCC cases, and microvessel density was evaluated by CD34 immunostaining. The results were further correlated with clinicopathological parameters. For 47 of 86 HCC cases, the CD66a expression showed diffuse membrane or cytoplasmic staining. The other 39 HCC cases revealed loss of CD66a expression. Loss of CD66a expression was statistically significantly associated with large tumor size (p=0.016), fatty change (p=0.039), patients with transcatheter arterial embolization (p=0.007), and high microvessel density (p=0.036). CD34 expression had no significant association with tumor size, virus infection, histological grade, and capsular invasion. The diffuse and cytoplasmic expression of CD66a may involve the early stage of the HCC, and the loss of CD66a expression indicates tumor progression. PMID- 27377844 TI - Impaired olfactory function in patients with polycystic ovary syndrome. AB - Polycystic ovary syndrome (PCOS) is an endocrine disorder which affects 6.6% of women of child-bearing age. Although olfactory dysfunction is frequent in the population and it negatively affects quality of life, neither physicians or patients consider this important. This case-control study included 30 patients diagnosed with PCOS, and 25 healthy age-matched controls. Sniffin' sticks tests (BurghartGmbH, Wedel, Germany) were used to analyze olfactory functions, and the Beck Depression Inventory was used to evaluate depressive symptoms. The total odor score was significantly lower in the PCOS group compared to the control group (p<0.005). The Beck depression score was higher in the PCOS group (p<0.005). There was a negative correlation between the total odor score and the Beck Depression Score. Patients with PCOS have impaired olfactory function. This might be related to depressive disorders that are also observed in those patients. PMID- 27377845 TI - Methotrexate treatment in progressive tubal ectopic pregnancies and hCG-related clinicosurgical implications. AB - Our aim was to evaluate the relationship between the success of methotrexate treatment and beta-hCG levels in progressive tubal ectopic pregnancies. We defined a retrospective cohort of 394 progressive tubal ectopic pregnancy patients treated with methotrexate. A single-dose methotrexate protocol using 50 mg/m(2) was administered to patients with progressive tubal ectopic pregnancy. Surgery was performed in patients who exhibited signs of acute abdomen due to tubal rupture. Of 394 patients that received methotrexate treatment, 335 (84.6%) responded to medical treatment, while the remaining 59 (15.36%) underwent surgery due to treatment failure. beta-hCG levels in the failure group were significantly higher as compared with the success group at Day 1, Day 4, and Day 7 (2116+/-3157 vs. 4178+/-3422, 2062+/-3551 vs. 4935+/-4103, and 1532+/-3007 vs. 3900+/-4783, respectively). The receiver operating characteristics curve for beta-hCG levels at Day 1 was 0.738, with a cutoff value of 1418 mIU/mL, while sensitivity and specificity values reached the optimum for treatment success (83.1% and 59.4%, respectively). Medical treatment with methotrexate achieved an 85.02% success rate for the treatment of progressive tubal ectopic pregnancy, while success rates for medical treatment decreased significantly when initial beta-hCG levels were >1418 mIU/mL. PMID- 27377846 TI - Augmentation enterocystoplasty without reimplantation for patients with neurogenic bladder and vesicoureteral reflux. AB - The objective of this study was to assess the clinical outcome of vesicoureteral reflux (VUR) after augmentation cystoplasty alone in patients with a hypocompliant neurogenic bladder. Between January 2009 and December 2014, 29 patients with a hypocompliant bladder associated with VUR confirmed by videourodynamics (VUD) preoperatively were recruited in this study. All patients had undergone bladder augmentation with a generous detubularized segment of bowel at our institution. No effort had been made to correct the existing reflux. Preoperative assessment included urinalysis, kidney function tests, ultrasonography, and videourodynamic evaluation. All patients had various degrees of VUR. The status of VUR and bladder function were studied by VUD. The mean follow-up period was 2.2 years (range 0.5-5.5 years). The VUD manifested a significant improvement of bladder capacity, diminution of intravesical pressure, and resolution of reflux after bladder augmentation. After the surgery, 24/29 (83%) no longer had reflux, 3/29 (10%) showed improvement in reflux, and 2/29 (7%) demonstrated no change in reflux. In addition, 16/21 (76%) patients had reflux Grades I-III; 100% patients with reflux Grades IV and V had complete cessation of reflux. Only one patient had symptomatic urinary infection after the surgery. Augmentation enterocystoplasty without ureteral reimplantation is thus effective and adequate for patients with high-pressure and hypocompliant neurogenic bladder. Therefore, ureteral reimplantation is not necessary when augmentation enterocystoplasty is recommended for patients with high-pressure, low-compliant bladder and VUR. PMID- 27377847 TI - Can the neutrophil-to-lymphocyte ratio be used to predict recurrence and progression of non-muscle-invasive bladder cancer? AB - The aim of our study was to evaluate whether neutrophil-to-lymphocyte ratio (NLR) is a predictor of disease progression and recurrence in patients with primary non muscle-invasive bladder cancer (NMIBC). This was a prospective study of 86 patients with newly diagnosed NMIBC. The patients were classified by the number of points assigned by the European Organization for Research and Treatment of Cancer risk tables. The correlation between progression score, recurrence score, age, mean platelet volume, red blood cell distribution width and NLR was assessed statistically. The same parameters were compared between the risk groups. A significant difference in NLR and age values was observed between recurrence and progression risk score groups. The relationships between NLR and recurrence and progression risk scores were no longer significant after correcting for the statistical effect of age on scores. Age was significantly different between groups after adjusting for NLR. Our study revealed that NLR and age were associated with patient age and bladder tumor progression and recurrence risk scores. After correcting for age, the significant relationship with NLR was lost, in contrast to some previous studies. We recommend that patient age should be corrected to avoid misleading results in NLR studies. PMID- 27377848 TI - Interference of diabetes on the association of gamma-glutamyl transpeptidase to platelet ratio with liver fibrosis in chronic hepatitis C. PMID- 27377849 TI - Novel treatment of symptomatic pontine Virchow-Robin space. PMID- 27377850 TI - MiR-124 suppresses the chemotactic migration of rat mesenchymal stem cells toward HGF by downregulating Wnt/beta-catenin signaling. AB - Mesenchymal stem cells (MSCs) exhibit the potential to repair a wide variety of injured adult tissues. The migration capability of MSCs is an important determinant of the efficiency of MSC transplant therapy. MicroRNAs (miRNAs) are increasingly implicated in regulating the migration of MSCs. Herein, we show that the expression of miR-124 was downregulated in rat MSCs (rMSCs) treated with hepatocyte growth factor (HGF). Overexpression of miR-124 significantly reduced the chemotactic migration of rMSCs toward HGF, while inhibition of endogenous miR 124 promoted the chemotactic migration. A further study revealed that miR-124 directly targeted FZD4 and LRP6, which encode a receptor and co-receptor of the Wnt/beta-catenin signaling pathway, respectively, thus reducing the activity of this signaling. Consistently, activation of the Wnt/beta-catenin signaling pathway by LiCl and DeltaN89beta-catenin rescued the inhibitory effect of miR-124 on the chemotactic migration of rMSCs toward HGF, while inhibition of Wnt/beta catenin signaling by FH535 abrogated the enhanced chemotactic response achieved by the miR-124 inhibitor. Collectively, our study demonstrates that miR-124 downregulates Wnt/beta-catenin signaling via targeting FZD4 and LRP6 and thus suppresses the chemotactic migration of rMSCs toward HGF. PMID- 27377851 TI - Modeling Na+-Ca2+ exchange in the heart: Allosteric activation, spatial localization, sparks and excitation-contraction coupling. AB - The cardiac sodium (Na+)/calcium (Ca2+) exchanger (NCX1) is an electrogenic membrane transporter that regulates Ca2+ homeostasis in cardiomyocytes, serving mainly to extrude Ca2+ during diastole. The direction of Ca2+ transport reverses at membrane potentials near that of the action potential plateau, generating an influx of Ca2+ into the cell. Therefore, there has been great interest in the possible roles of NCX1 in cardiac Ca2+-induced Ca2+ release (CICR). Interest has been reinvigorated by a recent super-resolution optical imaging study suggesting that ~18% of NCX1 co-localize with ryanodine receptor (RyR2) clusters, and ~30% of additional NCX1 are localized to within ~120nm of the nearest RyR2. NCX1 may therefore occupy a privileged position in which to modulate CICR. To examine this question, we have developed a mechanistic biophysically-detailed model of NCX1 that describes both NCX1 transport kinetics and Ca2+-dependent allosteric regulation. This NCX1 model was incorporated into a previously developed super resolution model of the Ca2+ spark as well as a computational model of the cardiac ventricular myocyte that includes a detailed description of CICR with stochastic gating of L-type Ca2+ channels and RyR2s, and that accounts for local Ca2+ gradients near the dyad via inclusion of a peri-dyadic (PD) compartment. Both models predict that increasing the fraction of NCX1 in the dyad and PD decreases spark frequency, fidelity, and diastolic Ca2+ levels. Spark amplitude and duration are less sensitive to NCX1 spatial redistribution. On the other hand, NCX1 plays an important role in promoting Ca2+ entry into the dyad, and hence contributing to the trigger for RyR2 release at depolarized membrane potentials and in the presence of elevated local Na+ concentration. Whole-cell simulation of NCX1 tail currents are consistent with the finding that a relatively high fraction of NCX1 (~45%) resides in the dyadic and PD spaces, with a dyad-to-PD ratio of roughly 1:2. Allosteric Ca2+ activation of NCX1 helps to "functionally localize" exchanger activity to the dyad and PD by reducing exchanger activity in the cytosol thereby protecting the cell from excessive loss of Ca2+ during diastole. PMID- 27377853 TI - Adolescent versus parent reports on asthma and asthma symptoms. AB - PURPOSE: Epidemiological studies of asthma in adolescence commonly rely on self reports. This study aimed to compare adolescent and parent reports regarding the presence of asthma and asthma symptoms in two ethnic groups, Jews and Arabs, living in the same country. METHODS: Eighth-grade pupils attending five schools in Tel Aviv and four schools in two Arab cities in Israel were asked to complete the self-report International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire in the classroom. Their parents were interviewed by telephone using the parental ISAAC questionnaire. We assessed prevalence rates of asthma and asthma symptoms according to adolescent and parent responses. Agreement between adolescents and parents was assessed by Cohen's kappa coefficient. RESULTS: Adolescents reported more asthma and asthma symptoms than their parents in both the Jewish (327 adolescent-parent pairs) and the Arab (335 adolescent-parent pairs) groups. Both groups showed moderate adolescent-parent chance-corrected agreement for current asthma (kappa 0.59 in Jews, 0.52 in Arabs, P = 0.60) and lifetime asthma (kappa 0.53 Jews, 0.44 in Arabs, P = 0.33); and slight to fair chance-corrected agreement for asthma symptoms. There were no statistically significant differences between the Jewish and Arab populations in chance corrected agreement for any of the parameters assessed. CONCLUSIONS: Jewish and Arab adolescents more often report asthma and asthma symptoms than do their parents. This seems to be a cross-cultural phenomenon. Therefore, particular attention should be paid to the source of information when comparing prevalence of asthma and asthma symptoms across studies. Pediatr Pulmonol. 2017;52:154-159. (c) 2016 Wiley Periodicals, Inc. PMID- 27377852 TI - In vivo label-free measurement of lymph flow velocity and volumetric flow rates using Doppler optical coherence tomography. AB - Direct in vivo imaging of lymph flow is key to understanding lymphatic system function in normal and disease states. Optical microscopy techniques provide the resolution required for these measurements, but existing optical techniques for measuring lymph flow require complex protocols and provide limited temporal resolution. Here, we describe a Doppler optical coherence tomography platform that allows direct, label-free quantification of lymph velocity and volumetric flow rates. We overcome the challenge of very low scattering by employing a Doppler algorithm that operates on low signal-to-noise measurements. We show that this technique can measure lymph velocity at sufficiently high temporal resolution to resolve the dynamic pulsatile flow in collecting lymphatic vessels. PMID- 27377854 TI - Pterostilbene-induced changes in gut microbiota composition in relation to obesity. AB - SCOPE: Nutritional interventions based on the use of natural bioactive compounds might offer new possibilities for reshaping obesity-associated bacterial dysregulation or dysbiosis and improving health. We evaluated whether pterostilbene supplementation could induce changes in gut microbiota composition and whether these modifications were associated with improvements in metabolic variables. METHODS AND RESULTS: Zucker (fa/fa) rats were given a standard diet supplemented (n = 10) or not (n = 9) with pterostilbene (15 mg/kg body weight/day) by oral gavage for 6 weeks. Faucal samples at the beginning and at the end of the intervention period were analyzed by Illumina Mi-Seq sequencing approach. Pterostilbene exerted protective antiobesity effects, improved metabolic function (insulin sensitivity), and induced structural changes in gut microbiota composition. A decrease in the levels of Firmicutes and an increase in Verrucomicrobia phyla were detected in the pterostilbene-treated group. Bacterial species belonging to genera Akkermansia and Odoribacter were also increased. A strong inverse correlation between Akkermansia muciniphila and body weight was evidenced. Odoribacter splanchnicus showed a negative correlation with adiposity. CONCLUSION: Pterostilbene modifies intestinal bacteria composition toward a healthier microbial profile and suggests that the antiobesity effects induced in Zucker rats could be associated with an enrichment of the mucin-degrading bacterial members, namely Akkermansia and Odoribacter genus. PMID- 27377855 TI - Safety of low-dose dabigatran in patients with atrial fibrillation and mild renal insufficiency. AB - BACKGROUND: Dabigatran etexilate (DE), an effective direct oral anticoagulant for patients with atrial fibrillation (AF), should be carefully used in patients with renal insufficiency. Data on the safety of DE in Japanese "real world" patients with mildly impaired renal function are limited. We hypothesized that low-dose DE (110mg, twice daily) could be safely used in Japanese AF patients with mildly impaired renal function compared to those with preserved renal function. METHODS AND RESULTS: One hundred ninety-six consecutive AF patients taking low-dose DE were retrospectively enrolled in this study, and were divided into two groups: preserved creatinine clearance (CCr >=50ml/min; n=127) and reduced CCr (30 49ml/min; n=69). Baseline characteristics including CHADS2, CHA2DS2-VASc, and HAS BLED scores were evaluated. Activated partial thromboplastin time (aPTT) was measured as a surrogate marker of the anticoagulant activity of DE, which was evaluated at 661 time points in total and the data were divided into five time windows after the last DE intake. The incidence of bleeding complications was compared between the two groups of reduced and preserved CCr. Reduced CCr group showed higher age (76.9+/-6.3 years vs. 67.6+/-6.7 years), higher CHADS2 (2.6+/ 1.4 vs. 1.8+/-1.2), higher CHA2DS2-VASc (4.3+/-1.6 vs. 3.2+/-1.6), and higher HAS BLED (2.3+/-1.0 vs. 2.0+/-1.0) scores in comparison with preserved CCr group (p<0.01, respectively). There was no difference in aPTT over the entire time windows between the two groups. The incidence of total bleeding events was not significantly different between the two groups (reduced vs. preserved CCr=2/69 vs. 2/127). CONCLUSION: Low-dose DE was safe in AF patients with mildly reduced CCr. PMID- 27377856 TI - Systematic reviews of factors associated with the onset and progression of neurological conditions in humans: A methodological overview. AB - As a component of the National Population Health Study of Neurological conditions, systematic reviews were conducted to identify risk factors associated with the onset and progression of 14 priority neurological conditions. Between 2011 and 2013, electronic databases and grey literature sources were searched to identify systematic reviews and primary studies reporting on the onset and progression of each condition. Inclusion was restricted to studies of humans reported in English or French. Additional condition-specific eligibility criteria were also applied. Titles and abstracts were screened by one reviewer with excluded records verified by a second reviewer. Full-text reports were screened independently by two reviewers. Disagreements were resolved by consensus or third party adjudication. Systematic reviews were quality appraised using the AMSTAR criteria, with only moderate and high quality reviews considered for inclusion. Primary studies were also sought to ensure that evidence from existing systematic reviews was supplemented with recent primary study findings (i.e., those published after the most recent systematic review). Evidence from primary studies was also considered if a systematic review was unavailable or of poor quality. Data were extracted using standardized forms. Where feasible, data were extracted independently by two reviewers. Otherwise, data were extracted by a single reviewer and independent data extraction by a second reviewer was conducted for a randomly selected sample of studies. An updated search was conducted in 2016 to identify systematic reviews published since the initial search in 2011-2013. A summary of the methodology used to conduct the systematic reviews is described. Illustrative results are provided for the risk of amyotrophic lateral sclerosis in relation to occupational exposure to lead and other heavy metals. PMID- 27377857 TI - Identification of risk factors associated with onset and progression of amyotrophic lateral sclerosis using systematic review and meta-analysis. AB - Although amyotrophic lateral sclerosis (ALS) was identified as a neurological condition 150 years ago, risk factors related to the onset and progression of ALS remain largely unknown. Monogenic mutations in over 30 genes are associated with about 10% of ALS cases. The age at onset of ALS and disease types has been found to influence ALS progression. The present study was designed to identify additional putative risk factors associated with the onset and progression of ALS using systematic review and meta-analysis of observational studies. Risk factors that may be associated with ALS include: 1) genetic mutations, including the intermediate CAG repeat expansion in ATXN2; 2) previous exposure to heavy metals such as lead and mercury; 3) previous exposure to organic chemicals, such as pesticides and solvents; 4) history of electric shock; 5) history of physical trauma/injury (including head trauma/injury); 6) smoking (a weak risk factor for ALS in women); and 6) other risk factors, such as participating in professional sports, lower body mass index, lower educational attainment, or occupations requiring repetitive/strenuous work, military service, exposure to Beta-N methylamino-l-alanin and viral infections. Risk factors that may be associated with ALS progression rate include: 1) nutritional status, including vitamin D deficiency; 2) comorbidities; 3) ethnicity and genetic factors; 4) lack of supportive care; and 4) smoking. The extent to which these associations may be causal is discussed, with further research recommended to strengthen the evidence on which determinations of causality may be based. PMID- 27377858 TI - Commentary: The Impact of Asking Intention or Self-Prediction Questions on Subsequent Behavior: A Meta-Analysis. PMID- 27377859 TI - Seawater-Assisted Self-Healing of Catechol Polymers via Hydrogen Bonding and Coordination Interactions. AB - It is highly desirable to prevent crack formation in polymeric materials at an early stage and to extend their lifespan, particularly when repairs to these materials would be difficult for humans. Here, we designed and synthesized catechol-functionalized polymers that can self-heal in seawater through hydrogen bonding and coordination. These bioinspired acrylate polymers are originally viscous materials, but after coordination with environmentally safe, common metal cations in seawater, namely, Ca(2+) and Mg(2+), the mechanical properties of the polymers were greatly enhanced from viscous to tough, hard materials. Reduced swelling in seawater compared with deionized water owing to the higher osmotic pressure resulted in greater toughness (~5 MPa) and self-healing efficiencies (~80%). PMID- 27377860 TI - Measurement of obesity prevention in childcare settings: A systematic review of current instruments. AB - OBJECTIVE: The incidence of childhood obesity is highest among children entering kindergarten. Overweight and obesity in early childhood track through adulthood. Programs increasingly target children in early life for obesity prevention. However, the published literature lacks a review on tools available for measuring behaviour and environmental level change in child care. The objective is to describe measurement tools currently in use in evaluating obesity-prevention in preschool-aged children. METHODS: Literature searches were conducted in PubMed using the keywords "early childhood obesity," "early childhood measurement," "early childhood nutrition" and "early childhood physical activity." Inclusion criteria included a discussion of: (1) obesity prevention, risk assessment or treatment in children ages 1-5 years; and (2) measurement of nutrition or physical activity. RESULTS: One hundred thirty-four publications were selected for analysis. Data on measurement tools, population and outcomes were abstracted into tables. Tables are divided by individual and environmental level measures and further divided into physical activity, diet and physical health outcomes. Recommendations are made for weighing advantages and disadvantages of tools. CONCLUSION: Despite rising numbers of interventions targeting obesity-prevention and treatment in preschool-aged children, there is no consensus for which tools represent a gold standard or threshold of accuracy. PMID- 27377861 TI - Dideoxy nucleoside triphosphate (ddNTP) analogues: Synthesis and polymerase substrate activities of pyrrolidinyl nucleoside triphosphates (prNTPs). AB - The dideoxynucleoside triphosphates (ddNTPs) terminate the bio-polymerization of DNA and become essential chemical component of DNA sequencing technology which is now basic tool for molecular biology research. In this method the radiolabeled or fluorescent dye labeled ddNTP analogues are being used for DNA sequencing by detection of the terminated DNA fragment after single labeled ddNTP incorporation into DNA under PCR conditions. This report describes the syntheses of rationally designed novel amino-functionalized ddNTP analogue such as Pyrrolidine nucleoside triphosphates (prNTPs), and their polymerase activities with DNA polymerase by LC MS and Gel-electrophoretic techniques. The Mass and PAGE analyses strongly support the incorporation of prNTPs into DNA oligonucleotide with Therminator DNA polymerase as like control substrate ddNTP. As resultant the DNA oligonucleotide are functionalized as amine group by prNTP incorporation with polymerase. Hence prNTPs provide opportunities to prepare demandable conjugated DNA with other biomolecules/dyes/fluorescence molecule without modifying nucleobase structure. PMID- 27377862 TI - Design, synthesis, and mode of action studies of a mitomycin tetramer inducing double activations with a single probe. AB - We report design, synthesis, and mechanistic studies of a new mitomycin tetramer 9 along with a new mitomycin dimer 10. Mitomycin 9 is a tetramer connected by the disulfide linker 11, and easily undergoes disulfide cleavage to provide two dimeric structures 9r that each contains a single thiol probe for activations. So, tetramer 9 as a precursor of 9r was specifically targeted to undergo double activations with a single probe. A tetramer 9 was synthesized using 1 and key intermediate 11, and a dimer 10 was synthesized from 1 and diamine 12. Activation studies revealed that 9 underwent effective double activations with a single probe by nucleophiles while the reference 10 did not. Evaluations of DNA ISC formations showed that 9 generated substantial levels of DNA ISC by nucleophilic activation while the references 10 and 2 did not. The effectiveness of 9 in activation and formation of DNA ISC per probe was verified by comparing with dimers 5-8 of double activations with two probes. These findings highlighted the role of a single thiol in 9r and demonstrated the intended double activations with a single probe, which marks the first case in mitomycin studies. PMID- 27377863 TI - Synthesis and biological investigation of new equatorial (beta) stereoisomers of 3-aminotropane arylamides with atypical antipsychotic profile. AB - A series of novel 3beta-aminotropane derivatives containing a 2-naphthalene or a 2-quinoline moiety was synthesised and evaluated for their affinity for 5-HT1A, 5 HT2A and D2 receptors. Their affinity for the receptors was in the nanomolar to micromolar range. p-Substitution (6c, 6f, 6i, 6l, 6o), as well as substitution with chlorine atoms (6g, 6h, 6i), led to a significant increase in binding affinity for D2 receptors with compounds 6f (Ki=0.6nM), 6c and 6i (Ki=0.4nM), having the highest binding affinities. m-Substituted derivatives were the most promising ligands in terms of 5-HT2A receptor binding affinity whereas 2 quinoline derivatives (10a, 10b) displayed the highest affinity for 5-HT1AR and were the most selective ligands with Ki=62.7nM and Ki=30.5nM, respectively. Finally, the selected ligands 6b, 6d, 6e, 6g, 6h, 6k, 6n and 6o, with triple binding activity for the D2, 5-HT1A and 5-HT2A receptors, were subjected to in vivo tests, such as those for induced hypothermia, climbing behaviour and the head twitch response, in order to determine their pharmacological profile. The tested ligands presented neither agonist nor antagonist properties for the 5-HT1A receptors in the induced hypothermia and lower lip retraction (LLR) tests. All tested compounds displayed antagonistic activity against 5-HT2A, with 6n and 6o being the most active. Four (6b, 6k, 6n and 6o) out of eight tested compounds could be classified as D2 antagonists. Additionally, evaluation of metabolic stability was performed for selected ligands, and introduction of halogen atoms into the benzene ring of 6h, 6k, 6n and 6o improved their metabolic stability. The project resulted in the selection of the lead compounds 6n and 6o, which had antipsychotic profiles, combining dopamine D2-receptor and 5-HT2A antagonism and metabolic stability. PMID- 27377864 TI - Kinetic and structural insights into the binding of histone deacetylase 1 and 2 (HDAC1, 2) inhibitors. AB - The structure-activity and structure-kinetic relationships of a series of novel and selective ortho-aminoanilide inhibitors of histone deacetylases (HDACs) 1 and 2 are described. Different kinetic and thermodynamic selectivity profiles were obtained by varying the moiety occupying an 11A channel leading to the Zn(2+) catalytic pocket of HDACs 1 and 2, two paralogs with a high degree of structural similarity. The design of these novel inhibitors was informed by two ligand-bound crystal structures of truncated hHDAC2. BRD4884 and BRD7232 possess kinetic selectivity for HDAC1 versus HDAC2. We demonstrate that the binding kinetics of HDAC inhibitors can be tuned for individual isoforms in order to modulate target residence time while retaining functional activity and increased histone H4K12 and H3K9 acetylation in primary mouse neuronal cell culture assays. These chromatin modifiers, with tuned binding kinetic profiles, can be used to define the relation between target engagement requirements and the pharmacodynamic response of HDACs in different disease applications. PMID- 27377865 TI - Boron-doped diamond electrooxidation of ethyl paraben: The effect of electrolyte on by-products distribution and mechanisms. AB - Ethyl paraben (EP), a representative emerging pollutant of the parabens family, was subject to electrochemical oxidation over a boron-doped diamond (BDD) anode. Experiments were carried out in a single-compartment cell at 10-70 mA cm-2 current density, 200-600 MUg L-1 EP concentration, initial solution pH 3-9 and 0.1 M electrolyte concentration. The degradation rate is favored at increased current densities and in the presence of NaCl as the supporting electrolyte, while the pH effect is inconsiderable. For instance, the first order rate constant for the degradation of 200 MUg L-1 EP at 30 mA cm-2 was 0.25, 0.1 and 0.07 min-1 with NaCl, Na2SO4 and HClO4, respectively. Degradation in secondary treated wastewater was faster than in pure water presumably due to the action of chloride ions present in the effluent. Liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) was employed to determine major transformation by products (TBPs). The route of EP degradation with Na2SO4 involves hydroxylation and demethylation reactions, signifying the role of electrogenerated hydroxyl radicals in the process. Twenty one TBPs were identified with NaCl as the electrolyte, including several chlorinated and non-chlorinated dimers and trimers; these findings suggest that indirect oxidation mediated by chlorine radicals and other chlorine active species also takes place. In this view, the role of the supporting electrolyte is crucial since it can influence both reaction kinetics and pathways. PMID- 27377866 TI - Biological invasions, ecological resilience and adaptive governance. AB - In a world of increasing interconnections in global trade as well as rapid change in climate and land cover, the accelerating introduction and spread of invasive species is a critical concern due to associated negative social and ecological impacts, both real and perceived. Much of the societal response to invasive species to date has been associated with negative economic consequences of invasions. This response has shaped a war-like approach to addressing invasions, one with an agenda of eradications and intense ecological restoration efforts towards prior or more desirable ecological regimes. This trajectory often ignores the concept of ecological resilience and associated approaches of resilience based governance. We argue that the relationship between ecological resilience and invasive species has been understudied to the detriment of attempts to govern invasions, and that most management actions fail, primarily because they do not incorporate adaptive, learning-based approaches. Invasive species can decrease resilience by reducing the biodiversity that underpins ecological functions and processes, making ecosystems more prone to regime shifts. However, invasions do not always result in a shift to an alternative regime; invasions can also increase resilience by introducing novelty, replacing lost ecological functions or adding redundancy that strengthens already existing structures and processes in an ecosystem. This paper examines the potential impacts of species invasions on the resilience of ecosystems and suggests that resilience-based approaches can inform policy by linking the governance of biological invasions to the negotiation of tradeoffs between ecosystem services. PMID- 27377867 TI - Shotgun Lipidomic Profiling of the NCI60 Cell Line Panel Using Rapid Evaporative Ionization Mass Spectrometry. AB - Rapid evaporative ionization mass spectrometry (REIMS) was used for the rapid mass spectrometric profiling of cancer cell lines. Spectral reproducibility was assessed for three different cell lines, and the extent of interclass differences and intraclass variance was found to allow the identification of these cell lines based on the REIMS data. Subsequently, the NCI60 cell line panel was subjected to REIMS analysis, and the resulting data set was investigated for its distinction of individual cell lines and different tissue types of origin. Information content of REIMS spectral profiles of cell lines were found to be similar to those obtained from mammalian tissues although pronounced differences in relative lipid intensity were observed. Ultimately, REIMS was shown to detect changes in lipid content of cell lines due to mycoplasma infection. The data show that REIMS is an attractive means to study cell lines involving minimal sample preparation and analysis times in the range of seconds. PMID- 27377868 TI - Lexical tone variation and spoken word recognition in preschool children: effects of perceptual salience. AB - Children undergo gradual progression in their ability to differentiate correct and incorrect pronunciations of words, a process that is crucial to establishing a native vocabulary. For the most part, the development of mature phonological representations has been researched by investigating children's sensitivity to consonant and vowel variation, with a much lesser focus on lexical tones. The current study investigates sensitivity to lexical tones in word recognition with specific attention to role of perceptual salience. Chinese-speaking preschoolers were presented with familiar words that were correctly pronounced, substituted for a subtle tone variant (Tones 2 and 3), or substituted for a salient tone variant (Tones 1 and 4). Results demonstrated that subtle tone variants were mistakenly perceived as correct pronunciations and only salient tone variants were recognized as mispronunciations. Findings suggest that tone integration follows a more complex developmental course that previously concluded. PMID- 27377869 TI - MicroRNA-26a-interleukin (IL)-6-IL-17 axis regulates the development of non alcoholic fatty liver disease in a murine model. AB - Non-alcoholic fatty liver disease (NAFLD) is a hepatic presentation of obesity and metabolic syndrome. MicroRNA 26a (Mir-26a) has been reported to play functions in cellular differentiation, cell growth, cell apoptosis and metastasis. A recent paper indicated that Mir-26a regulated insulin sensitivity and metabolism of glucose and lipids. However, the role of Mir-26a in NAFLD still needs to be investigated further. In our current study, vectors encoding pre-Mir 26a (LV-26a) and an empty lentiviral vector (LV-Con) delivered approximately 2 * 107 transforming units of recombinant lentivirus were injected into mice through the tail vein. LV-26a-infected mice were protected from glucose dysmetabolism and showed markedly decreased total liver weight, hepatic triglyceride deposition and serum alanine transaminase (ALT) concentration when compared with LV-Con-treated mice. LV-26a-treated mice also exhibited decreased infiltration of immune cells in the liver - something attributed to reduce infiltration of T cell receptor (TCR)-gammadelta+ , granulocyte-differentiation antigen-1 (Gr-1)+ cells and CD11b+ cells. Next, we found that Mir-26a inhibited the expression of interleukin (IL)-17 and IL-6 in vivo and in vitro. Furthermore, the decreased expression of IL-17 in the liver tissue induced by Mir-26a was abrogated completely by IL-6 overexpression. The decreased total liver weight, hepatic triglyceride deposition and serum ALT concentration induced by Mir-26a was also abrogated completely by IL-6 over-expression. In conclusion, the Mir-26a-IL-6-IL-17 axis regulates the development of NAFLD in a murine model. PMID- 27377871 TI - Iron Kinetics and Evolution of Microbial Populations in Low-pH, Ferrous Iron Oxidizing Bioreactors. AB - Iron-rich, acidic wastewaters are commonplace pollutants associated with metal and coal mining. Continuous-flow bioreactors were commissioned and tested for their capacities to oxidize ferrous iron in synthetic and actual acid mine drainage waters using (initially) pure cultures of the recently described acidophilic, iron-oxidizing heterotrophic bacterium Acidithrix ferrooxidans grown in the presence of glucose and yeast extract. The bioreactors became rapidly colonized by this bacterium, which formed macroscopic streamer growths in the flowing waters. Over 97% of ferrous iron in pH 2.0-2.2 synthetic mine water was oxidized (at up to 225 mg L(-1) h(-1)) at dilution rates (D) of 0.6 h(-1). Rates of iron oxidation decreased with pH but were still significant, with influent liquors as low as pH 1.37. When fed with actual mine water, >90% of ferrous iron was oxidized at D values of 0.4 h(-1), and microbial communities within the bioreactors changed over time, with Atx. ferrooxidans becoming increasingly displaced by the autotrophic iron-oxidizing acidophiles Ferrovum myxofaciens, Acidithiobacillus ferrivorans, and Leptospirillum ferrooxidans (which were all indigenous to the mine water), although this did not have a negative impact on net ferrous-iron oxidation. The results confirmed the potential of using a heterotrophic acidophile to facilitate the rapid commissioning of iron-oxidizing bioreactors and illustrated how microbial communities within them can evolve without compromising the performances of the bioreactors. PMID- 27377870 TI - p66Shc: A novel biomarker of tubular oxidative injury in patients with diabetic nephropathy. AB - Increased p66Shc expression has been associated with diabetic nephropathy (DN). However, whether p66Shc can serve as a potential biomarker for tubular oxidative injury in DN is unknown. We measured the expression of p66Shc in peripheral blood monocytes (PBMs) and renal biopsy tissues from DN patients and then analysed the relationship between p66Shc expression and the clinical characteristics of patients with DN. Patients were divided into 4 groups (class IIa, class IIb, class III and the control group). qPCR, Western blotting and immunohistochemistry were performed. The results showed that both p66Shc and p-p66Shc expression significantly increased in PBMs and kidney tissues of DN patients. Moreover, Spearman's correlation and multiple regression analyses were carried out. A positive relationship between the p66Shc expression and oxidative stress was found. p66Shc and oxidative stress were significant predictors of the degree of tubular damage. In addition, p66Shc expression was positively correlated with the concentrations of beta-NAG, UACR and 8-OHdG, low-density lipoprotein and blood glucose levels, and duration of diabetes in patients with DN from class IIa to class III. These data indicated that increased expression of p66Shc may serve as a therapeutic target and a novel biomarker of DN. PMID- 27377872 TI - The surface sulfur doping induced enhanced performance of cobalt catalysts in oxygen evolution reactions. AB - A novel surface sulfur (S) doped cobalt (Co) catalyst for the oxygen evolution reaction (OER) is theoretically designed through the optimisation of the electronic structure of highly reactive surface atoms which is also validated by electrocatalytic OER experiments. PMID- 27377873 TI - Multivariate Bayesian variable selection exploiting dependence structure among outcomes: Application to air pollution effects on DNA methylation. AB - The analysis of multiple outcomes is becoming increasingly common in modern biomedical studies. It is well-known that joint statistical models for multiple outcomes are more flexible and more powerful than fitting a separate model for each outcome; they yield more powerful tests of exposure or treatment effects by taking into account the dependence among outcomes and pooling evidence across outcomes. It is, however, unlikely that all outcomes are related to the same subset of covariates. Therefore, there is interest in identifying exposures or treatments associated with particular outcomes, which we term outcome-specific variable selection. In this work, we propose a variable selection approach for multivariate normal responses that incorporates not only information on the mean model, but also information on the variance-covariance structure of the outcomes. The approach effectively leverages evidence from all correlated outcomes to estimate the effect of a particular covariate on a given outcome. To implement this strategy, we develop a Bayesian method that builds a multivariate prior for the variable selection indicators based on the variance-covariance of the outcomes. We show via simulation that the proposed variable selection strategy can boost power to detect subtle effects without increasing the probability of false discoveries. We apply the approach to the Normative Aging Study (NAS) epigenetic data and identify a subset of five genes in the asthma pathway for which gene-specific DNA methylations are associated with exposures to either black carbon, a marker of traffic pollution, or sulfate, a marker of particles generated by power plants. PMID- 27377874 TI - VCP746, a novel A1 adenosine receptor biased agonist, reduces hypertrophy in a rat neonatal cardiac myocyte model. AB - VCP746 is a novel A1 adenosine receptor (A1 AR) biased agonist previously shown to be cytoprotective with no effect on heart rate. The aim of this study was to investigate the potential anti-hypertrophic effect of VCP746 in neonatal rat cardiac myocytes (NCM). NCM hypertrophy was stimulated with interleukin (IL) 1beta (10 ng/mL), tumour necrosis factor (TNF)-alpha (10 ng/mL) or Ang II (100 nmol/L) and was assessed by (3) H-leucine incorporation assay. VCP746 significantly inhibited IL-1beta-, TNF-alpha- and Ang II-stimulated NCM hypertrophy as determined by (3) H-leucine incorporation. The anti-hypertrophic effect of VCP746 was also more potent than that of the prototypical A1 AR agonist, N(6) -cyclopentyladenosine (CPA). Further investigation with the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay showed that neither CPA nor VCP746 had any effect on cell viability, confirming that the reduction in (3) H-leucine incorporation mediated by CPA and VCP746 was not due to a reduction in cell viability. IL-1beta, TNF-alpha and Ang II were also shown to increase the mRNA expression of hypertrophy biomarkers, ANP, beta MHC and alpha-SKA in NCM. Treatment with VCP746 at concentrations as low as 1 nmol/L suppressed mRNA expression of ANP, beta-MHC and alpha-SKA stimulated by IL 1beta, TNF-alpha or Ang II, demonstrating the broad mechanistic basis of the potent anti-hypertrophic effect of VCP746. This study has shown that the novel A1 AR agonist, VCP746, is able to attenuate cardiac myocyte hypertrophy. As such, VCP746 is potentially useful as a pharmacological agent in attenuating cardiac remodelling, especially in the post-myocardial infarction setting, given its previously established cytoprotective properties. PMID- 27377875 TI - Reply. PMID- 27377876 TI - Reply. PMID- 27377878 TI - Study on the interaction between anti-tuberculosis drug ethambutol and bovine serum albumin: multispectroscopic and cyclic voltammetric approaches. AB - The binding of bovine serum albumin (BSA) to ethambutol (EMB) was investigated using spectroscopic methods, viz., fluorescence, Fourier transform infrared (FTIR), ultraviolet (UV)/vis absorption and cyclic voltammetry techniques. Spectroscopic analysis of the emission quenching at different temperatures revealed that the quenching mechanism of serum albumin by EMB is static, which was also confirmed by lifetime measurements. The number of binding sites, n, and binding constant, K, were obtained at various temperatures. The distance, r, between EMB and the protein was evaluated according to the Forster energy transfer theory. Based on displacement experiments using site probes, viz., warfarin, ibuprofen and digitoxin, the site of binding of EMB in BSA was proposed to be Sudlow's site I. The effect of EMB on the conformation of BSA was analyzed by using synchronous fluorescence spectra (SFS) and 3D fluorescence spectra. The results of fluorescence, UV/vis absorption and FTIR spectra showed that the conformation of BSA was changed in the presence of EMB. The thermodynamic parameters including enthalpy change (DeltaH0 ), entropy change (DeltaS0 ) and free energy change (DeltaG0 ) for BSA-EMB were calculated according to the van't Hoff equation and are discussed. PMID- 27377877 TI - Anti-Osteoporosis Medication Prescriptions and Incidence of Subsequent Fracture Among Primary Hip Fracture Patients in England and Wales: An Interrupted Time Series Analysis. AB - In January 2005, the National Institute for Health and Care Excellence (NICE) in England and Wales provided new guidance on the use of antiosteoporosis therapies for the secondary prevention of osteoporotic fractures. This was shortly followed in the same year by market authorization of a generic form of alendronic acid within the UK. We here set out to estimate the actual practice impact of these events among hip fracture patients in terms of antiosteoporosis medication prescribing and subsequent fracture incidence using primary care data (Clinical Practice Research Datalink) from 1999 to 2013. Changes in level and trend of prescribing and subsequent fracture following publication of NICE guidance and availability of generic alendronic acid were estimated using an interrupted time series analysis. Both events were considered in combination within a 1-year "intervention period." We identified 10,873 primary hip fracture patients between April 1999 and Sept 2012. Taking into account prior trend, the intervention period was associated with an immediate absolute increase of 14.9% (95% CI, 10.9 to 18.9) for incident antiosteoporosis prescriptions and a significant and clinically important reduction in subsequent major and subsequent hip fracture: 0.19% (95% CI, -0.28 to -0.09) and -0.17% (95% CI, -0.26 to -0.09) per 6 months, respectively. This equated to an approximate 14% (major) and 22% (hip) reduction at 3 years postintervention relative to expected values based solely on preintervention level and trend. We conclude that among hip fracture patients, publication of NICE guidance and availability of generic alendronic acid was temporally associated with increased prescribing and a significant decline in subsequent fractures. (c) 2016 American Society for Bone and Mineral Research. PMID- 27377879 TI - Lymph node image-guided core-needle biopsy for cutaneous T-cell lymphoma staging. PMID- 27377880 TI - Self-propelled swimming of a flexible plunging foil near a solid wall. AB - Numerical simulations are conducted to investigate the influences of a solid wall on the self-propelled swimming of a flexible plunging foil. It is found that the presence of a solid wall enhances the cruising speed, with the cost of increasing input power. Rigid foil can achieve high percentage increase in cruising speed when swimming near a solid wall, but the propulsive efficiency may be reduced. Foils with some flexibility can enjoy the enhancements in both cruising speed and propulsive efficiency. Another advantage of the flexible foils in near-wall swimming is that smaller averaged lateral forces are produced. The effects of wall confinement on the wake structure and the vortex dynamics are also studied in this paper. The results obtained in this study shed some light on the unsteady wall effect experienced by aquatic animals and also inform the design of bio mimetic underwater vehicles which are capable of exploiting the wall effect. PMID- 27377881 TI - Autophagy-related intrinsically disordered proteins in intra-nuclear compartments. AB - Recent analyses indicated that autophagy can be regulated via some nuclear transcriptional networks and many important players in the autophagy and other forms of programmed cell death are known to be intrinsically disordered. To this end, we analyzed similarities and differences in the intrinsic disorder distribution of nuclear and non-nuclear proteins related to autophagy. We also looked at the peculiarities of the distribution of the intrinsically disordered autophagy-related proteins in various intra-nuclear organelles, such as the nucleolus, chromatin, Cajal bodies, nuclear speckles, promyelocytic leukemia (PML) nuclear bodies, nuclear lamina, nuclear pores, and perinucleolar compartment. This analysis revealed that the autophagy-related proteins constitute about 2.5% of the non-nuclear proteins and 3.3% of the nuclear proteins, which corresponds to a substantial enrichment by about 32% in the nucleus. Curiously, although, in general, the autophagy-related proteins share similar characteristics of disorder with a generic set of all non-nuclear proteins, chromatin and nuclear speckles are enriched in the intrinsically disordered autophagy proteins (29 and 37% of these proteins are disordered, respectively) and have high disorder content at 0.24 and 0.27, respectively. Therefore, our data suggest that some of the nuclear disordered proteins may play important roles in autophagy. PMID- 27377882 TI - Cross-linguistic transfer effects after phonologically based cognate therapy in a case of multilingual specific language impairment (SLI). AB - BACKGROUND: Clinicians globally recognize as exceptionally challenging the development of effective intervention practices for bi- or multilingual children with specific language impairment (SLI). Therapy in both or all of an impaired child's languages is rarely possible. An alternative is to develop treatment protocols that facilitate the transfer of therapy effects from a treated language to an untreated language. AIMS: To explore whether cognates, words that share meaning and phonological features across languages, could be used to boost lexical retrieval in the context of multilingual SLI. This is dependent on exploiting the phonological information in the one, trained language as a mechanism for (phonological) language transfer to the other, untrained languages. METHODS & PROCEDURES: The participant is an 8.5-year-old girl diagnosed with SLI who showed a severe naming deficit in her three spoken languages (Bulgarian, English and Greek). She received training on cognates (n = 20) using a picture based naming task in English only, three times a week, over a 4-week period for 20 min each time. Phonological-based naming therapy was carried out using form based strategies. OUTCOMES & RESULTS: There was a significant improvement during therapy and immediately after intervention on cognate performance in English which was maintained 1 month after intervention. Cognate production in Bulgarian and Greek also improved during all stages of the intervention. Improvement in the non-treated languages was slightly more than half of the improvement recorded in English. The findings reflected some degree of cross-linguistic transfer effects. CONCLUSIONS & IMPLICATIONS: Cross-linguistic transfer effects were evident during therapy and after therapy had finished and the effects were maintained 1 month post-treatment. Both the native language (Bulgarian) and the dominant language (Greek) benefitted equally from the treatment of cognates in English. Generalization to non-treatment words was evident, predominantly for English. The results suggest that cognates can indeed be used successfully as a WFD intervention strategy for multilingual children with SLI with lasting effects. PMID- 27377883 TI - Can acaricide-impregnated leg bands fitted to female red grouse reduce sheep tick parasitization of chicks and increase chick survival? AB - In parts of northern England, North Wales and the Scottish Highlands, increasing numbers of sheep ticks Ixodes ricinus (Ixodida: Ixodidae), and the louping ill virus they can carry, are considered to be important factors that reduce red grouse Lagopus lagopus scotica productivity. The present study tested this hypothesis by fitting adult female grouse with leg bands impregnated with the acaricide cypermethrin to experimentally control ticks on their chicks on two managed grouse moors in northeast Scotland. The chicks of females fitted with acaricide leg bands showed reduced tick infestations and improved survival in one of the two study years, relative to chicks of control females. Acaricide leg bands constitute a potential management technique that may be adopted by grouse moor managers in circumstances of high tick infestations on grouse chicks. PMID- 27377884 TI - Can an anti-Xa assay for low-molecular-weight heparin be used to assess the presence of rivaroxaban? AB - BACKGROUND: Due to the convenience afforded by the lack of required laboratory monitoring, direct oral anticoagulants (DOACs) are increasingly used as alternatives to Vitamin-K antagonists for certain medical conditions. However, there are circumstances in which assessment of DOAC plasma concentrations may be helpful in guiding clinical decisions, including patients presenting with either bleeding or thrombosis, or patients requiring urgent invasive procedures. Evaluating the anticoagulant effects of DOACs is often difficult because of the limited availability of DOAC-specific assays in most laboratories. OBJECTIVE: To evaluate the correlation between ex vivo plasma concentrations of rivaroxaban and a chromogenic anti-Xa assay for low-molecular-weight heparin (LMWH) routinely used in our coagulation laboratory. MATERIALS AND METHODS: Twenty-nine blood samples from 20 patients anticoagulated with rivaroxaban (dose; 10-20 mg/day) were evaluated using an anti-Xa assay for LMWH and results were correlated with rivaroxaban plasma concentrations using a rivaroxaban specific assay. RESULTS: A linear dose-dependent relationship was demonstrated between plasma concentrations of rivaroxaban and the chromogenic anti-Xa assay for LMWH (R2 = 0.92). PT and PTT demonstrated poor correlations (R2 = 0.03; and R2 = 0.01, respectively) with rivaroxaban plasma concentrations. CONCLUSION: Findings from this study suggest that if specific assays for rivaroxaban are unavailable, then the chromogenic anti-Xa assay for LMWH may be useful for assessing the anticoagulant effects of rivaroxaban. PMID- 27377885 TI - Letter to the editor for "Update of the human and mouse Fanconi anemia genes". PMID- 27377886 TI - Dispersive Liquid-Liquid Microextraction Combined with High-Performance Liquid Chromatography for the Simultaneous Analysis of Matrine Alkaloids in Traditional Chinese Medicine. AB - Dispersive liquid-liquid microextraction (DLLME), coupled with high-performance liquid chromatography (HPLC), was developed and introduced for simultaneous extraction and determination of the trace level matrine alkaloids (oxymatrine, matrine, sophoridine and oxysophocarpine) in Composite Kushen Injection and Sophorae Flavescentis Radix. Several factors affecting performance were investigated and optimized, including type and volume of extraction solvent, type and volume of disperser solvent, sample phase pH, shaking time, centrifugation time and rate, and salt concentration in the sample solution. Under optimized conditions, the enrichment factors of DLLME for four matrine alkaloids ranged from 0.17 to 83.5; the good linearities were obtained for all analytes with the coefficient of determination of between 0.9924 and 0.9989; the limits of detection were between 0.2 and 275 ng mL-1; the satisfactory recoveries (86.6 104.5%) and the precision (relative standard deviation (RSD) 2.0-12.2%) were also achieved. The average content of sophoridine, oxymatrine, matrine and oxysophocarpine in Composite Kushen Injection and Sophorae Flavescentis Radix are 0.60, 40.3, 0.17, 0.39 mg mL-1 with the RSD of 5.3-9.0% (n = 3), and 0.13, 26.7, 1.20, 0.40 mg g-1 with the RSD of 3.5-9.2% (n = 3). The experimental results showed that the method was a simple, sensitive and practical for simultaneous extracting, enriching and quantifying of the different concentrations level matrine alkaloids in TCM. PMID- 27377887 TI - A Rapid and Validated RP-HPLC Method for the Simultaneous Quantification of Benzoic Acid, Metronidazole and Miconazole Nitrate in Vaginal Formulations. AB - A rapid, specific, precise and accurate reversed-phase high-performance liquid chromatography method has been developed and validated for the determination of benzoic acid, metronidazole and miconazole nitrate in vaginal formulations of cream and tablet (excluding benzoic acid). The validation was carried out with reference to ICH guidelines. The chromatography was carried out on a Zorbax SB-CN column (250 * 4.6 mm, 5 um) linear gradient elution with mixture of solvent A (phosphate buffer) and solvent B (acetonitrile) as a mobile phase at the flow rate of 1.0 mL/min and dual mode of detection that is 233 nm for benzoic acid and miconazole nitrate and 319 nm for metronidazole. The limit of detection and limit of quantification are 1.07, 0.79 and 0.62 MUg/mL and 3.23, 2.40 and 1.88 MUg/mL for benzoic acid, metronidazole and miconazole nitrate, respectively. The linearity of benzoic acid, metronidazole and miconazole nitrate showed a correlation coefficient of 0.9997, 0.9995 and 0.9993, respectively. The good results were achieved with respect to repeatability of relative standard deviation <=2% and recovery within 98.0-102.0%. The selected column in this study performed well. The method is simple, accurate and precise, and may be recommended for routine quality control test for any dosage forms containing benzoic acid, metronidazole and miconazole nitrate. PMID- 27377888 TI - Rapid Fingerprint Analysis of Flos Carthami by Ultra-Performance Liquid Chromatography and Similarity Evaluation. AB - Flos Carthami (FC), the dried flower of Carthamus tinctorius L., has widely been used for the treatment of cardiovascular diseases in China. A rapid fingerprint analysis method of FC was established by ultra-performance liquid chromatography (UPLC) for the quality control. The analysis time was shortened by 45 min, from 75 min on conventional high-performance liquid chromatography (HPLC) to 30 min on UPLC. Ten batches of FC samples from various sources were analyzed by the UPLC method. Coexisting peaks in FC chromatograms were chosen to calculate their relative retention time (RRT) and relative peak area (RPA). Thirteen characteristic peaks were illustrated on UPLC fingerprints. In the 24-h stability test, the relative standard deviation (RSD) for the RRT and RPA was <0.08% and 4.41%, respectively. The RSD for precision of the RRT and RPA was <0.05% and 4.26%, respectively. And the RSD for repeatability was <0.05% for the RRT and 3.91% for the RPA. The similarities of the 10 batches of FC were ranged from 0.938 to 0.995.Compared with the HPLC method, UPLC provided shorter analysis time, higher resolution and better separation performance, which is feasible for the quality control of FC. PMID- 27377890 TI - Confidentiality, anonymity and amnesty for midwives in distress seeking online support - Ethical? AB - BACKGROUND: Midwife health is intrinsically linked to the quality of safe patient care. To ensure safe patient care, there is a need to deliver emotional support to midwives. One option that midwives may turn to may be a confidential online intervention, instead of localised, face-to-face support. RESEARCH DESIGN: Following the Realist And MEta-narrative Evidence Syntheses: Evolving Standards publication standards, this realist synthesis approach explores the ethical considerations in permitting confidentiality, anonymity and amnesty in online interventions to support midwives in work-related psychological distress. An iterative search methodology was used to select nine papers for review. To assimilate information, papers were examined for ideas relating to ethical dimensions of online interventions to support midwives in work-related psychological distress. This review takes a narrative approach. FINDINGS: Online interventions can support the development of insight, help seeking and open discussion. Additionally, Internet support groups can become morally persuasive in nature. Anonymity and confidentiality are both effective and therapeutic features of online interventions when used in collaboration with effective online moderation. Yet, ethical dilemmas remain where users cannot be identified. DISCUSSION: Confidentiality and anonymity remain key components of successful online interventions. However, sanctioning the corollary component of amnesty may provoke moral discomfort for those seeking immediate accountability. For others, amnesty is seen as essential for open disclosure and help seeking. Ultimately, the needs of midwives must be balanced with the requirement to protect the public and the professional reputation of midwifery. CONCLUSION: In supporting midwives online, the principles of anonymity, confidentiality and amnesty may evoke some resistance on ethical grounds. However, without offering identity protection, it may not be possible to create effective online support services for midwives. The authors of this article argue that the principles of confidentiality, anonymity and amnesty should be upheld in the pursuit of the greatest benefit for the greatest number of people. PMID- 27377889 TI - An international study comparing conventional versus mRNA level testing (TargetPrint) for ER, PR, and HER2 status of breast cancer. AB - To compare results from messenger RNA (mRNA)-based TargetPrint testing with those from immunohistochemistry (IHC) and in situ hybridization (ISH) conducted according to local standard procedures at hospitals worldwide. Tumor samples were prospectively obtained from 806 patients at 22 hospitals. The mRNA level of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) was assessed by TargetPrint quantitative gene expression readouts. IHC/ISH assessments were performed according to local standards at the participating hospitals. TargetPrint readout showed a high concordance with IHC/ISH of 95 % (kappa 0.81) for ER, 81 % (kappa 0.56) for PR, and 94 % (kappa 0.76) for HER2. The positive/negative agreement between TargetPrint and IHC for ER, PR, and HER2 was 96 %/87 %, 84 %/74 %, and 74 %/98 %, respectively. The concordance rate in IHC/ISH results between hospitals varied: 88-100 % for ER (kappa 0.50-1.00); 50-100 % for PR (kappa 0.20-1.00); and 90-100 % for HER2 (kappa 0.59-1.00). mRNA readout of ER, PR, and HER2 status by TargetPrint was largely comparable to local IHC/ISH analysis. However, there was substantial discordance in IHC/ISH results between different hospitals. When results are discordant, the use of TargetPrint would improve the reliability of hormone receptor and HER2 results by prompting retesting in a reference laboratory. PMID- 27377891 TI - A Metabolic Inhibitory Cocktail for Grave Cancers: Metformin, Pioglitazone and Lithium Combination in Treatment of Pancreatic Cancer and Glioblastoma Multiforme. AB - Pancreatic cancer (PC) and glioblastoma multiforme (GBM) are among the human cancers with worst prognosis which require an urgent need for efficient therapies. Here, we propose to apply to treat both malignancies with a triple combination of drugs, which are already in use for different indications. Recent studies demonstrated a considerable link between risk of PC and diabetes. In experimental models, anti-diabetogenic agents suppress growth of PC, including metformin (M), pioglitazone (P) and lithium (L). L is used in psychiatric practice, yet also bears anti-diabetic potential and selectively inhibits glycogen synthase kinase-3 beta (GSK-3beta). M, a biguanide class anti-diabetic agent shows anticancer activity via activating AMP-activated protein kinase (AMPK). Glitazones bind to PPAR-gamma and inhibit NF-kappaB, triggering cell proliferation, apoptosis resistance and synthesis of inflammatory cytokines in cancer cells. Inhibition of inflammatory cytokines could simultaneously decrease tumor growth and alleviate cancer cachexia, having a major role in PC mortality. Furthermore, mutual synergistic interactions exist between PPAR-gamma and GSK 3beta, between AMPK and GSK-3beta and between AMPK and PPAR-gamma. In GBM, M blocks angiogenesis and migration in experimental models. Very noteworthy, among GBM patients with type 2 diabetes, usage of M significantly correlates with better survival while reverse is true for sulfonylureas. In experimental models, P synergies with ligands of RAR, RXR and statins in reducing growth of GBM. Further, usage of P was found to be lesser in anaplastic astrocytoma and GBM patients, indicating a protective effect of P against high-grade gliomas. L is accumulated in GBM cells faster and higher than in neuroblastoma cells, and its levels further increase with chronic exposure. Recent studies revealed anti invasive potential of L in GBM cell lines. Here, we propose that a triple-agent regime including drugs already in clinical usage may provide a metabolic adjuvant therapy for PC and GBM. PMID- 27377893 TI - Combined infection training-a pioneering collaborative approach to educating infection specialists. AB - This commentary discusses the recent pioneering overhaul of training for UK doctors wishing to pursue a career in the infection specialities. Changes include the introduction of new curricula that embrace increased collaboration between the laboratory-based and clinical specialties and a broad-based infection training period, named 'Combined Infection Training', which has never been seen before. Here, we discuss the benefits and challenges associated with the collaborative approach to training with particular reference to points that educators responsible for training programme design need to consider. We also describe our own local experiences in adopting a proactive, multidisciplinary approach to address potential obstacles prospectively. PMID- 27377892 TI - Profiling networks of distinct immune-cells in tumors. AB - BACKGROUND: It is now clearly evident that cancer outcome and response to therapy is guided by diverse immune-cell activity in tumors. Presently, a key challenge is to comprehensively identify networks of distinct immune-cell signatures present in complex tissue, at higher-resolution and at various stages of differentiation, activation or function. This is particularly so for closely related immune-cells with diminutive, yet critical, differences. RESULTS: To predict networks of infiltrated distinct immune-cell phenotypes at higher resolution, we explored an integrated knowledge-based approach to select immune cell signature genes integrating not only expression enrichment across immune cells, but also an automatic capture of relevant immune-cell signature genes from the literature. This knowledge-based approach was integrated with resources of immune-cell specific protein networks, to define signature genes of distinct immune-cell phenotypes. We demonstrate the utility of this approach by profiling signatures of distinct immune-cells, and networks of immune-cells, from metastatic melanoma patients who had undergone chemotherapy. The resultant bioinformatics strategy complements immunohistochemistry from these tumors, and predicts both tumor-killing and immunosuppressive networks of distinct immune cells in responders and non-responders, respectively. The approach is also shown to capture differences in the immune-cell networks of BRAF versus NRAS mutated metastatic melanomas, and the dynamic changes in resistance to targeted kinase inhibitors in MAPK signalling. CONCLUSIONS: This integrative bioinformatics approach demonstrates that capturing the protein network signatures and ratios of distinct immune-cell in the tumor microenvironment maybe an important factor in predicting response to therapy. This may serve as a computational strategy to define network signatures of distinct immune-cells to guide immuno-pathological discovery. PMID- 27377894 TI - A human pathogenic bacterial infection model using the two-spotted cricket, Gryllus bimaculatus. AB - Invertebrate animal species that can withstand temperatures as high as 37 degrees C, the human body temperature, are limited. In the present study, we utilized the two-spotted cricket, Gryllus bimaculatus, which lives in tropical and subtropical regions, as an animal model of human pathogenic bacterial infection. Injection of Pseudomonas aeruginosa or Staphylococcus aureus into the hemolymph killed crickets. Injected P. aeruginosa or S. aureus proliferated in the hemolymph until the cricket died. The ability of these pathogenic bacteria to kill the crickets was blocked by the administration of antibiotics. S. aureus gene-knockout mutants of virulence factors, including cvfA, agr and srtA, exhibited decreased killing ability compared with the parent strain. The dose at which 50% of crickets were killed by P. aeruginosa or S. aureus was not decreased at 37 degrees C compared with that at 27 degrees C. Injection of Listeria monocytogenes, which upregulates toxin expression at 37 degrees C, killed crickets, and the dose at which 50% of crickets were killed was decreased at 37 degrees C compared with that at 27 degrees C. These findings suggest that the two-spotted cricket is a useful model animal for evaluating the virulence properties of various human pathogenic bacteria at variable temperature including 37 degrees C. PMID- 27377896 TI - Effects of combination approach on harm reduction programs: the Taiwan experience. AB - BACKGROUND: In 2003, a major epidemic of human immunodeficiency virus emerged among injection drug users in Taiwan. In response to the twin epidemics of HIV and intravenous drug addiction, the government implemented comprehensive harm reduction programs beginning in 2005. Collected data from relevant agencies were used to explore the impact of the harm reduction programs on HIV and illicit drug use. METHODS: This study divided 2002-2015 into three intervention phases and used the surveillance data and statistics on the HIV epidemic, drug abuse, and the intervention from relevant agencies to explore the correlations between different variables in different intervention periods and the combination effects of interventions on the HIV epidemic. RESULTS: In the pre-intervention phase, the growth of the HIV epidemic followed the rapidly increasing number of heroin users, reaching a peak in 2005. After the initiation of harm reduction programs, the HIV epidemic ceased growing, even rapidly declining with the expansion of needle and syringe exchange programs and opioid substitution therapy; however, the number of heroin users remained high. When the implementation of the needle and syringe exchange programs and the opioid substitution therapy program reached the plateau level in the consolidation phase, the number of heroin users also decreased rapidly. The combination effects of the harm reduction programs in this period also pushed levels of HIV infection below those before this outbreak. CONCLUSIONS: The HIV epidemic among injection drug users incorporates the dual problems of drug addiction and needle-sharing behaviors, so the use of a single intervention will not resolve all of the problems. Facing a severe HIV epidemic among injection drug users, quickly scaling up and promoting comprehensive harm reduction programs is a good strategy that can be used to simultaneously reverse the HIV epidemic and to resolve the illicit drug use problems. More research is needed to find out the reasons behind why there were cases that declined opioid substitution therapy, so that efforts can be undertaken to avoid the epidemic rebounding. PMID- 27377895 TI - A neomorphic cancer cell-specific role of MAGE-A4 in trans-lesion synthesis. AB - Trans-lesion synthesis (TLS) is an important DNA-damage tolerance mechanism that permits ongoing DNA synthesis in cells harbouring damaged genomes. The E3 ubiquitin ligase RAD18 activates TLS by promoting recruitment of Y-family DNA polymerases to sites of DNA-damage-induced replication fork stalling. Here we identify the cancer/testes antigen melanoma antigen-A4 (MAGE-A4) as a tumour cell specific RAD18-binding partner and an activator of TLS. MAGE-A4 depletion from MAGE-A4-expressing cancer cells destabilizes RAD18. Conversely, ectopic expression of MAGE-A4 (in cell lines lacking endogenous MAGE-A4) promotes RAD18 stability. DNA-damage-induced mono-ubiquitination of the RAD18 substrate PCNA is attenuated by MAGE-A4 silencing. MAGE-A4-depleted cells fail to resume DNA synthesis normally following ultraviolet irradiation and accumulate gammaH2AX, thereby recapitulating major hallmarks of TLS deficiency. Taken together, these results demonstrate a mechanism by which reprogramming of ubiquitin signalling in cancer cells can influence DNA damage tolerance and probably contribute to an altered genomic landscape. PMID- 27377897 TI - Incidences of acute kidney injury, dialysis, and graft loss following intravenous administration of low-osmolality iodinated contrast in patients with kidney transplants. AB - PURPOSE: To determine the incidence of acute kidney injury (AKI), need for emergent dialysis, and renal graft loss in patients with kidney transplants, who underwent CT examinations with low-osmolality iodine-based contrast material (IBCM). MATERIALS AND METHODS: Our institutional review board approved this retrospective Health Insurance Portability and Accountability Act compliant study. From January 2005 to April 2015, a total of 224 CT examinations were performed using low-osmolality IBCM in patients with kidney transplants. Six patients who had septic or cardiogenic shock and 30 patients with documented, failed transplants were excluded from our analysis, yielding a total of 188 examinations. Of these, pre- and post-CT serum creatinine (SCr) values were available for 104 examinations, to allow evaluation of AKI. The mean baseline SCr and estimated glomerular filtration rate (eGFR) in this subgroup were 1.37 mg/dL (median 1.18, range 0.5-6.05) and 65.8 mL/min/1.73 m2, respectively (median 65, range 9-114). AKI was defined as a rise in SCr of either (a) >=0.3 mg/dL or (b) >=0.5 mg/dL in the 24- to 72-h period following IBCM administration. For all patients undergoing the 188 examinations, need for dialysis and graft loss 30 days after contrast administration were evaluated. RESULTS: In patients with pre- and post-CT SCr values, the incidence of AKI was 7% (7/104) based on a rise of >=0.3 mg/dL and 3% (3/104) based on a rise of >=0.5 mg/dL. All three patients with the more strict definition (>=0.5 mg/dL) had a pre-CT eGFR <60 mL/min/1.73 m2. No patient required dialysis or had renal graft loss 30 days after contrast administration. CONCLUSION: The incidence of AKI after administration of low osmolality IBCM administration in renal transplant recipients is low, with no instances of emergent dialysis or graft loss at 30 days post contrast. PMID- 27377898 TI - Imaging, endoscopy, and pathologic findings of primary gastritis cystica polyposa: description of a rare entity in a small case series. AB - OBJECTIVE: The purpose of this study is to describe a small case series of primary gastritis cystica polyposa (GCP) and explore its imaging features, endoscopic findings, and pathological manifestations. METHODS: In this institutional review board-approved, HIPAA-compliant, retrospective study, an electronic pathology database in our hospital was searched for all cases of GCP from July 2008 to December 2015, yielding five cases with both radiological and endoscopic examination. The characteristics of imaging and gastroscopy were explored, and the pathological basis was analyzed. RESULTS: All five cases of GCP occurred in a previously unoperated stomach, which underwent unenhanced CT and enhanced CT, and one of which underwent unenhanced MRI and enhanced MRI as well. Gastroscopy or gastroscopic ultrasound was performed on all five patients. Four submucosal cystic lesions were displayed, including three with low-attenuation liquid, and one with high-attenuation liquid on CT. Another lesion showed soft tissue mass attenuation protruding into the gastric cavity. The surface mucosal layers of all five lesions were smooth and obviously enhanced, with unenhanced cystic component inside. Four submucosal lesions were confirmed by gastroscopy. Gastroscopic ultrasound indicated anechoic area in the center of the lesion. A large mass-like lesion had protruded into the gastric cavity, and gastroscopic ultrasound indicated dispersed anechoic areas in the lesion. All Histopathological analyses indicated mild or moderate epithelial dysplasia, and cystic dilation of the gastric glands in the submucosal layers and lamina propria, surrounded by the infiltration of inflammatory cells. CONCLUSION: Primary GCP has relatively particular endoscopy features, which can be accurately diagnosed by gastroscopy when the lesion is small. But endoscopy has its limitations in the diagnosis and differentiation for some large lesions. In contrast to gastroscopy and gastroscopic ultrasound, CT or MRI provides more information about both the gastric wall and the extragastric extent of the disease, which is more helpful for differential diagnosis and surgical planning of GCP before operation. PMID- 27377899 TI - Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in colorectal liver metastasis: the radiologist's perspective. AB - PURPOSE: Hepatic resection is the only potentially curative treatment for patients with colorectal liver metastasis (CRLM). Many multidisciplinary approaches, including the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure, have been proposed to increase the resectability rate in these patients. ALPPS is the most recently described staged liver resection technique, representing an advantageous strategy to induce a rapid and marked increase in the future liver remnant (FLR) volume. The aim of this article is to describe the radiological evaluation of this procedure and its variation. METHODS: This retrospective study included 9 patients with CRLM who underwent the ALPPS procedure. Abdominal imaging studies were reviewed, with an emphasis on a rational radiological approach. The number of liver metastases, the FLR volume (pre- and postportal vein ligation), anatomical variations, potential pitfalls related to disease progression, and postoperative complications were evaluated. RESULTS: The types of hepatic resection included 4 classical ALPPS cases, 3 right ALPPS variations, and 2 left ALPPS variations. The mean FLR volume calculated in the initial evaluation was 453 mL (213-790 mL). Following the first surgery, the mean FLR volume increased to 634 mL (410-957 mL), which indicated a mean volume increase of 181.1 mL (95% CI 149.7-212.5 mL; p < 0.001) and a mean absolute volume increase of 48% (19%-88%). CONCLUSION: The ALPPS procedure is an emerging form of two-stage hepatectomy. In this context, radiologists should provide crucial preoperative and perioperative information that may change surgical planning and contribute to an improvement in the oncologic outcome. PMID- 27377900 TI - Reduced-Intensity Conditioning with Fludarabine, Cyclophosphamide, and Rituximab Is Associated with Improved Outcomes Compared with Fludarabine and Busulfan after Allogeneic Stem Cell Transplantation for B Cell Malignancies. AB - Reduced-intensity conditioning (RIC) has been used increasingly for allogeneic hematopoietic cell transplantation to minimize transplant-related mortality while maintaining the graft-versus-tumor effect. In B cell lymphoid malignancies, reduced-intensity regimens containing rituximab, an antiCD20 antibody, have been associated with favorable survival; however, the long-term outcomes of rituximab containing versus nonrituximab-containing regimens for allogeneic hematopoietic cell transplantation in B cell lymphoid malignancies remain to be determined. We retrospectively analyzed 94 patients who received an allogeneic transplant for a B cell lymphoid malignancy. Of these, 33 received RIC with fludarabine, cyclophosphamide, and rituximab (FCR) and graft-versus-host disease (GVHD) prophylaxis with a calcineurin inhibitor and mini-methotrexate, and 61 received RIC with fludarabine and busulfan (FluBu) and GVHD prophylaxis with a calcineurin inhibitor and mycophenolate mofetil. The 2-year overall survival was superior in patients who received FCR versus FluBu (72.7% versus 54.1%, P = .031), and in multivariable analysis adjusted for Disease Risk Index and donor type, only the conditioning regimen (FluBu versus FCR: HR, 2.06; 95% CI, 1.04 to 4.08; P = .037) and Disease Risk Index (low versus intermediate/high: HR, .38; 95% CI, .17 to .86; P = .02) were independent predictors of overall survival. The 2-year cumulative incidence of chronic GVHD was lower in patients who received FCR versus FluBu (24.2% versus 51.7%, P = .01). There was no difference in rate of relapse/progression or acute GVHD. Our results demonstrate that the use of RIC with FCR and GVHD prophylaxis with a calcineurin inhibitor and mini-methotrexate is associated with decreased chronic GVHD and improved overall survival. PMID- 27377903 TI - Response. PMID- 27377901 TI - Long-Term Outcomes after Treatment with Clofarabine +/- Fludarabine with Once Daily Intravenous Busulfan as Pretransplant Conditioning Therapy for Advanced Myeloid Leukemia and Myelodysplastic Syndrome. AB - Pretransplant conditioning regimens critically determine outcomes in the setting of allogeneic stem cell transplantation (allo-SCT). The use of nucleoside analogs such as fludarabine (Flu) in combination with i.v. busulfan (Bu) has been shown to be highly effective as a pretransplant conditioning regimen in acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS). Because leukemia relapse remains the leading cause of death after allo SCT, we studied whether clofarabine (Clo), a nucleoside analog with potent antileukemia activity, can be used to complement Flu. In a preliminary report, we previously showed the safety and efficacy of Clo +/- Flu with i.v. Bu in 51 patients with high-risk AML, CML, and MDS. The study has now been completed, and we present long-term follow-up data on the entire 70-patient population, which included 49 (70%), 8 (11%), and 13 (19%) patients with AML, MDS, and CML, respectively. Thirteen patients (19%) were in complete remission, and 41 patients (59%) received matched unrelated donor grafts. Engraftment was achieved in all patients. Sixty-three patients (90%) achieved complete remission. There were no deaths reported at day +30, and the 100-day nonrelapse mortality rate was 4% (n = 3). Thirty-one percent of patients (n = 22) developed grades II to IV acute graft versus-host disease, and the median overall survival and progression-free survival times were 2.4 years and .9 years, respectively. Our results confirm the safety and overall and progression-free survival advantage of the arms with higher Clo doses and lower Flu doses, which was most prominent in the AML/MDS group. PMID- 27377902 TI - ATF2 predicts poor prognosis and promotes malignant phenotypes in renal cell carcinoma. AB - BACKGROUND: Activating transcription factor 2 (ATF2) is a basic helix-loop-helix transcription factor, which has been shown to participate in the pathobiology of numerous cancers. However, the role of ATF2 in renal cell carcinoma (RCC) remains unclear. METHODS: ATF2 knockdown and overexpression studies were performed in RCC cells to evaluate changes in cell viability, cell cycle, apoptosis, migration and invasion. Xenograft models were used to examine the tumorigenic and metastatic capability of RCC cells upon ATF2 suppression. The expression of ATF2 in human RCC samples was determined using immunohistochemistry on a tissue microarray. RESULTS: ATF2 knockdown in RCC cells reduced their proliferative and metastatic potentials, whereas ATF2 overexpression enhanced these properties. Mechanistic studies revealed that the transcription of CyclinB1, CyclinD1, Snail and Vimentin was directly regulated by ATF2 in RCC cells. Moreover, ATF2 was shown to be highly expressed in RCC tissues, especially in tumors with metastases. High expression of ATF2 correlated with aggressive clinico-pathological characteristics and predicted poor prognosis of RCC patients. CONCLUSIONS: ATF2 exerts an oncogenic role in RCC and could serve as an important prognostic biomarker. PMID- 27377904 TI - RE: RNA Disruption Assay as a Biomarker of Pathological Complete Response in Neoadjuvant Trastuzumab-Treated Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. PMID- 27377905 TI - Accuracy of diagnostic tests for prosthetic joint infection: a systematic review. AB - PURPOSE: There are few evidence-based recommendations on the most effective methods for diagnosing prosthetic joint infections (PJIs), and the potency of tests in relation to each other also remains vague. This systematic review aimed to (1) identify systematic reviews reporting accuracies of available approaches for diagnosing PJI, (2) critically appraise their quality and bias, and (3) compare the available approaches in terms of accuracy for diagnosing PJI. METHODS: PubMed and EMBASE databases were searched for meta-analyses reporting accuracies of different diagnostic modalities for PJIs. Thirteen systematic reviews met the inclusion and exclusion criteria, and their data were extracted and tabulated by two reviewers in duplicate and independent manners. RESULTS: The 13 articles reported diagnostic accuracy from 278 clinical studies comprising 27,754 patients and evaluating 13 diagnostic tests grouped into 7 broad categories. Implant sonication had the highest positive likelihood ratio (17.2), followed by bacteriology (15.3) and synovial fluid differentiated cytology (13.3). The highest negative likelihood ratio was for interleukin (IL)-6 serum marker (0.03) followed by synovial fluid cytology and differentiation (0.12 and 0.13, respectively). CONCLUSION: The diagnostic tests that are most likely to rule out PJI include serum IL-6, serum C-reactive protein, and synovial fluid cytology. On the other hand, the diagnostic test that is most likely to confirm PJI is implant sonication. Nuclear imaging showed low overall accuracy as diagnostic tests for PJI. The findings of this study could enable clinicians to confirm or rule out PJIs using the most accurate, rapid, least invasive, and cost effective tools available, thereby enabling fast treatment before formation of resistant biofilms and degradation of patient conditions. LEVEL OF EVIDENCE: Systematic review, Level IV. PMID- 27377906 TI - Osteosynthesis versus endoprosthesis for the treatment of femoral neck fracture in Asian elderly patients. AB - BACKGROUND: The purpose of this study was to compare the clinical results between osteosynthesis and endoprosthesis for femoral neck fractures in asian elderly patients, and to analysis the factors that may affect the failure of osteosynthesis. METHODS: A retrospective review of 382 hips over 65-year old with femoral neck fracture was done. Within non-displaced fracture group, 81 cases (56.6 %) underwent internal fixation (IF) and with 62 cases (43.3 %) having bipolar hemiarthroplasty (BPHA). As for displaced fracture group, 60 cases (25.1 %) underwent internal fixation (IF) with 179 cases (74.8 %) having BPHA. Average follow-up period for the patients was 36.8 months. Analysis was conducted on complications depending on fracture types and osteoporosis, and clinical evaluation was done on gait capability by using Koval walking ability. RESULTS: In non-displaced group, BPHA group showed statistically significant lower percentage of complications compared to IF group, but re-operation rate and the degradations of Koval score were no significant differences. In displaced group, complication, re-operation rate and the degradations of Koval score of BPHA group were statistically better than those of IF group. Association between osteoporosis and non-union is no statistically significant. CONCLUSIONS: Endoprosthetic replacement could be a primary option for displaced femoral neck fracture in elderly asian patients. The choice of surgical treatment methods of non-displaced fracture in elderly asian patients should be determined carefully considering the age and the presence of osteoporosis. PMID- 27377907 TI - Bone alkaline phosphatase as a surrogate marker of bone metastasis in gastric cancer patients. AB - BACKGROUND: Bone metastasis is relatively uncommon in gastric cancer patients, but its incidence has been rising. Early detection of bone metastasis is important in preventing complications related to bone metastasis such as pain, fracture and the compromise of chemotherapy. In this pilot study, we investigated the feasibility of bone turnover markers as surrogate markers of bone metastasis in gastric cancer patients. METHODS: Fifty-eight patients with gastric cancer were included in this study. Serum levels of bone alkaline phosphatase (ALP), parathyroid hormone (PTH), 25(OH) D, osteocalcin (OC) and C terminal telopeptide were measured and compared between patients with bone metastasis and those without. Student's t-test and Mann-Whitney U test were used in comparing two groups, and Spearman's rank order correlation coefficient was calculated to quantify the strength of the associations. RESULTS: Fifty eight age- and sex matched patients were evaluated for bone turnover markers, among whom 29 patients had bone metastasis and 29 patients with no bone metastasis. The median age was 62 and there were 20 (68.9 %) males and 9 (31.1 %) females in each group. Bone ALP was significantly higher in the patient group (57.32 +/- 46.83 vs. 34.57 +/- 21.57, P = 0.037) than control group. Bone ALP was positively associated with ALP, osteocalcin, CA19-9, CA 72-4 and negatively associated with 25(OH) D. According to ROC-curve analysis, at the threshold value of 29.60 MUg/L, the sensitivity of bone ALP was 76.7 % and the specificity was 59.4 %. CONCLUSION: Bone ALP may be a surrogate marker of bone metastasis in gastric cancer patients. More prospective studies are warranted to determine the optimal bone turnover markers in the evaluation of bone metastasis. PMID- 27377908 TI - Is the tenofovir based therapy almighty for previous treatment failure in chronic hepatitis B? PMID- 27377909 TI - Transarterial chemoembolization versus resection for intermediate-stage (BCLC B) hepatocellular carcinoma. AB - BACKGROUND/AIMS: Several studies have suggested that surgical resection (SR) can provide a survival benefit over transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) at the intermediate stage according to the Barcelona Clinic Liver Cancer (BCLC) staging system. However, the criteria for SR remain to be determined. This study compared the long-term outcome of intermediate-stage HCC patients treated by either TACE or SR as a primary treatment modality, with the aim of identifying the patient subgroup that gained a survival benefit by either modality. METHODS: In total, 277 BCLC intermediate stage HCC patients treated by either TACE (N=225) or SR (N=52) were analyzed. RESULTS: The overall median survival time was significantly better for SR than TACE (61 vs. 30 months, P=0.002). Decisiontree analysis divided patients into seven nodes based on tumor size and number, serum alpha-fetoprotein (AFP) level, and Child-Pugh score, and these were then simplified into four subgroups (B1-B4) based on similarities in the overall hazard rate. SR provided a significant survival benefit in subgroup B2, characterized by 'oligo' (2-4) nodules of intermediate size (5-10 cm) when the AFP levels was <400 ng/ml, or 'oligo' (2-4) nodules of small to intermediate size (<10 cm) plus a Child-Pugh score of 5 when the AFP level was >=400 ng/mL (median survival 73 vs. 28 months for SR vs. TACE respectively; P=0.014). The survival rate did not differ significantly between SR and TACE in the other subgroups (B1 and B3). CONCLUSION: SR provided a survival benefit over TACE in intermediate-stage HCC, especially for patients meeting certain criteria. Re-establishing the criteria for optimal treatment modalities in this stage of HCC is needed to improve survival rates. PMID- 27377910 TI - Efficacy and safety of daclatasvir and asunaprevir for hepatitis C virus genotype 1b infection. AB - BACKGROUND/AIMS: The treatment strategy for hepatitis C virus (HCV) has been changing rapidly since the introduction of direct-acting antivirals such as daclatasvir (DCV) and asunaprevir (ASV). We evaluated the efficacy and safety of DCV and ASV for HCV in real-life practice. METHODS: Patients were treated with 60 mg of DCV once daily plus 200 mg of ASV twice daily for 24 weeks, and followed for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks after treatment (SVR12) and safety. RESULTS: This retrospective study included eight patients with chronic HCV genotype 1b infection. All of the enrolled patients were diagnosed with liver cirrhosis, and their mean age was 65.75 years. One patient was a nonresponder and two patients relapsed with previous pegylated interferon (PegIFN) and ribavirin (RBV) treatment. None of the patient showed NS5A mutation. An SVR12 was achieved in 88% of cases by the DCV and ASV combination therapy. The serum transaminase level and the aspartate aminotransferase-to-platelet ratio were improved after the treatment. DCV and ASV were well tolerated in most of the patients, with treatment discontinuation due to adverse events (elevated liver enzyme and decompensation) occurring in two patients. CONCLUSION: In this study, combination of DCV and ASV treatment achieved a high sustained virological response with few adverse events even in those with cirrhosis, advanced age, and nonresponse/relapse to previous interferon-based therapy. Close monitoring of safety issues may be necessary when treating chronic HCV patients receiving DCV and ASV, especially in older patient and those with cirrhosis. PMID- 27377911 TI - Tenofovir-associated nephrotoxicity in patients with chronic hepatitis B: two cases. AB - Tenofovir disoproxil fumarate (TDF) is effective against chronic hepatitis B (CHB) infection and its use is increasing rapidly worldwide. However, it has been established that TDF is associated with renal toxicity in human immunodeficiency virus-infected patients, while severe or symptomatic TDF-associated nephrotoxicity has rarely been reported in patients with CHB. Here we present two patients with TDF-associated nephrotoxicity who were being treated for CHB infection. The first patient was found to have clinical manifestations of proximal renal tubular dysfunction and histopathologic evidence of acute tubular necrosis at 5 months after starting TDF treatment. The second patient developed acute kidney injury at 17 days after commencing TDF, and he was found to have membranoproliferative glomerulonephritis with acute tubular injury. The renal function improved in both patients after discontinuing TDF. We discuss the risk factors for TDF-associated renal toxicity and present recommendations for monitoring renal function during TDF therapy. PMID- 27377912 TI - Undifferentiated embryonal sarcoma of the liver in an adult patient. AB - Undifferentiated embryonal sarcoma of the liver (UESL) is rare primary hepatic sarcoma and is known to occur in pediatric patients. This case is the UESL occurred in a 51-year old male patient. Multilocular cystic lesion was composed of primitive spindle cells without specific differentiation. This rare case would help to review differential diagnosis of primary sarcoma in liver and cystic neoplasm of the liver. PMID- 27377913 TI - Residential proximity to traffic and female pubertal development. AB - BACKGROUND: Traffic-related air pollution (TRAP) has been linked with several adverse health outcomes, including preterm birth and low birth weight, which are both related to onset of puberty. No studies to date have investigated the association between TRAP and altered pubertal timing. OBJECTIVE: Determine the association between residential proximity to traffic, as a marker of long-term TRAP exposure, and age at pubertal onset in a longitudinal study of girls. METHODS: We analyzed data for 437 girls at the CYGNET study site of the Breast Cancer and Environment Research Program. TRAP exposure was assessed using several measures of residential proximity to traffic based on address at study entry. Using accelerated failure time models, we calculated time ratios (TRs) and their corresponding 95% confidence intervals (CIs) for specified traffic metrics and pubertal onset, defined as stage 2 or higher for breast or pubic hair development (respectively, B2+ and PH2+). Models were adjusted for race/ethnicity, household income, and cotinine levels. RESULTS: At baseline, 71% of girls lived within 150m of a major road. The median age of onset was 10.3years for B2+ and 10.9years for PH2+. Living within 150m downwind of a major road was associated with earlier onset of PH2+ (TR 0.96, 95% CI 0.93, 0.99). Girls in the highest quintile of either distance-weighted traffic density, annual average daily traffic, and/or traffic density also reached PH2+ earlier than girls in the lowest quintiles. CONCLUSIONS: In this first study to assess the association between residential proximity to traffic and pubertal onset we found girls with higher exposure reached one pubertal milestone several months earlier than low exposed girls, even after consideration of likely confounders. Results should be expanded in larger epidemiological studies, and with measured levels of air pollutants. PMID- 27377914 TI - Estimated Prestroke Peak VO2 Is Related to Circulating IGF-1 Levels During Acute Stroke. AB - Background Insulin-like growth factor-1 (IGF-1) is neuroprotective after stroke and is regulated by insulin-like binding protein-3 (IGFBP-3). In healthy individuals, exercise and improved aerobic fitness (peak oxygen uptake; peak VO2) increases IGF-1 in circulation. Understanding the relationship between estimated prestroke aerobic fitness and IGF-1 and IGFBP-3 after stroke may provide insight into the benefits of exercise and aerobic fitness on stroke recovery. Objective The purpose of this study was to determine the relationship of IGF-1 and IGFBP-3 to estimated prestroke peak VO2 in individuals with acute stroke. We hypothesized that (1) estimated prestroke peak VO2 would be related to IGF-1 and IGFBP-3 and (2) individuals with higher than median IGF-1 levels will have higher estimated prestroke peak VO2 compared to those with lower than median levels. Methods Fifteen individuals with acute stroke had blood sampled within 72 hours of hospital admission. Prestroke peak VO2 was estimated using a nonexercise prediction equation. IGF-1 and IGFBP-3 levels were quantified using enzyme-linked immunoassay. Results Estimated prestroke peak VO2 was significantly related to circulating IGF-1 levels (r = .60; P = .02) but not IGFBP-3. Individuals with higher than median IGF-1 (117.9 ng/mL) had significantly better estimated aerobic fitness (32.4 +/- 6.9 mL kg-1 min-1) than those with lower than median IGF-1 (20.7 +/- 7.8 mL kg-1 min-1; P = .03). Conclusions Improving aerobic fitness prior to stroke may be beneficial by increasing baseline IGF-1 levels. These results set the groundwork for future clinical trials to determine whether high IGF-1 and aerobic fitness are beneficial to stroke recovery by providing neuroprotection and improving function. PMID- 27377916 TI - Intestinal perforation during chemotherapeutic treatment of intra-abdominal desmoid tumor in patients with Gardner's syndrome: report of two cases. AB - BACKGROUND: A minority of intra-abdominal desmoid tumors is associated with Gardner's syndrome in which desmoid tumors become an important cause of morbidity and mortality if they are surgically unresectable. CASE PRESENTATION: Here, we report two cases of intestinal perforation during chemotherapy in patients with Gardner's syndrome-associated intra-abdominal desmoids. One female and one male patients who developed inoperable desmoids were given the chemotherapeutic regimen of doxorubicin plus dacarbazine, followed by meloxicam. Significant tumor regression was observed clinically. However, intestinal perforation happened in both patients. They were subjected to emergency surgery, follow-up management, and survived up to now. CONCLUSIONS: The doxorubicin plus dacarbazine chemotherapy is an effective treatment for intra-abdominal demoid tumors in patients with Gardner's syndrome. On the other hand, given severe adverse events might occur, clinicians should pay more attention that tumor quick regression may cause intestinal perforation in which urgent surgical intervention is necessary. PMID- 27377917 TI - Magnetic resonance imaging for distinguishing ovarian clear cell carcinoma from high-grade serous carcinoma. AB - BACKGROUND: To compare the magnetic resonance imaging (MRI) features of ovarian clear cell carcinoma (CCC) and high-grade serous carcinoma (HGSC), to distinguish CCC from HGSC. METHODS: MRI features (laterality, shape, size, configuration, papillary projection, signal intensity, enhancement, peritoneal implant, lymphadenopathy, ascites) of 40 tumors in 37 patients with CCC, confirmed by surgery and pathology, were compared with those of 62 tumors in 40 patients with HGSC. Statistical analysis was performed using Mann-Whitney and Fisher's exact tests. RESULTS: There was a statistically significant difference in the mean maximum diameter, laterality, and FIGO stage (P = 0.002, P < 0.001, P < 0.001, respectively) between CCC and HGSC. Compared to HGSCs, CCCs were more frequently oval (30/40, 75 % vs 12/62, 19 %; P < 0.001), more often cystic (21/40, 53 % vs 8/62, 13 %; P < 0.001) and unilocular (23/29, 79 % vs 7/31, 23 %; P < 0.001), had T1-hyperintense cystic components more often (18/29, 62 % vs 5/29, 17 %; P < 0.001), had larger papillary projections (5.13 +/- 0.4 cm vs 2.91 +/- 0.3 cm; P < 0.001), were peritoneally implanted less frequently (P = 0.001) and had fewer ascites (P < 0.001). CONCLUSIONS: CCC typically showed an oval, unilocular cystic mass with large papillary projection and T1-hyperintense cystic components. MRI could be helpful for distinguishing CCC from HGSC. PMID- 27377915 TI - Sex-biased gene expression and sequence conservation in Atlantic and Pacific salmon lice (Lepeophtheirus salmonis). AB - BACKGROUND: Salmon lice, Lepeophtheirus salmonis (Copepoda: Caligidae), are highly important ectoparasites of farmed and wild salmonids, and cause multi million dollar losses to the salmon aquaculture industry annually. Salmon lice display extensive sexual dimorphism in ontogeny, morphology, physiology, behavior, and more. Therefore, the identification of transcripts with differential expression between males and females (sex-biased transcripts) may help elucidate the relationship between sexual selection and sexually dimorphic characteristics. RESULTS: Sex-biased transcripts were identified from transcriptome analyses of three L. salmonis populations, including both Atlantic and Pacific subspecies. A total of 35-43 % of all quality-filtered transcripts were sex-biased in L. salmonis, with male-biased transcripts exhibiting higher fold change than female-biased transcripts. For Gene Ontology and functional analyses, a consensus-based approach was used to identify concordantly differentially expressed sex-biased transcripts across the three populations. A total of 127 male-specific transcripts (i.e. those without detectable expression in any female) were identified, and were enriched with reproductive functions (e.g. seminal fluid and male accessory gland proteins). Other sex-biased transcripts involved in morphogenesis, feeding, energy generation, and sensory and immune system development and function were also identified. Interestingly, as observed in model systems, male-biased L. salmonis transcripts were more frequently without annotation compared to female-biased or unbiased transcripts, suggesting higher rates of sequence divergence in male-biased transcripts. CONCLUSIONS: Transcriptome differences between male and female L. salmonis described here provide key insights into the molecular mechanisms controlling sexual dimorphism in L. salmonis. This analysis offers targets for parasite control and provides a foundation for further analyses exploring critical topics such as the interaction between sex and drug resistance, sex-specific factors in host-parasite relationships, and reproductive roles within L. salmonis. PMID- 27377919 TI - Client perspectives on an Aboriginal community led oral health service in rural Australia. AB - OBJECTIVE: An oral health service was implemented, using a unique community development approach, for Northern NSW Australian Aboriginal communities in 2013 14. This study examined the views of children (and parents) who accessed the service, including: the extent of reported dental problems, oral health knowledge, attitudes and behaviour, accessibility of oral health services, satisfaction and cultural sensitivity of the service. METHODS: A survey of the children who accessed this service was conducted between October 2014 and December 2014. RESULTS: A total of 49 (71%) Aboriginal children aged 4-14 (or parents of), provided responses to the survey. All agreed that healthy teeth were important (100%), but many thought oral disease leading to extraction was normal (68%). High levels of oral pain were reported (66%), half (53%) reported brushing morning and night. Access to the new dental health service was reported as 'easy' (92%). Many walked (47%) or were driven (35%) in <30 min (90%). All respondents were happy with their dental treatment, and that their Aboriginal heritage was respected by the oral health team (100%). CONCLUSION: The implementation of a new community led oral health service to Northern NSW Aboriginal communities was shown here to be well-utilised, respected and in an area of high need. The collaborative approach could be continued to be utilised to implement targeted, community led health promotion programs to facilitate and encourage better oral health practices for the Aboriginal children in these communities. PMID- 27377918 TI - Self-assembled targeted nanoparticles based on transferrin-modified eight-arm polyethylene glycol-dihydroartemisinin conjugate. AB - Poor delivery of insoluble anticancer drugs has so far precluded their clinical application. In this study, an efficient tumor targeted-nanoparticle delivery system, transferrin-eight-arm-polyethylene glycol-dihydroartemisinin nanoparticles (TF-8arm-PEG-DHA NPs) for the vehiculation of dihydroartemisinin (DHA) was first prepared and evaluated for its targeting efficiency and cytotoxicity in vitro and in vivo to Lewis lung carcinoma (LLC) cells, which overexpress transferrin receptors (TFRs). The synthesized TF-8arm-PEG-DHA NPs had high solubility (~102 fold of free DHA), relatively high drug loading (~10 wt% DHA), long circulating half-life and moderate particle size (~147 nm). The in vitro cytotoxicity and in vivo tumor growth inhibition studies in LLC-tumor bearing mice confirmed the enhanced efficacy of TF-modified 8arm-PEG-DHA NPs compared to free DHA and non-modified 8arm-PEG-DHA NPs. All these results together supported that the formulation developed in this work exhibited great potential as an effective tumor targeting delivery system for insoluble anticancer drugs. PMID- 27377920 TI - HEMS in Alpine Rescue for Pediatric Emergencies. AB - OBJECTIVE: The objective of this study was to describe the pediatric emergencies encountered by the Christophorus-1 helicopter emergency medical service (HEMS) during a period of 2 years. METHODS: Emergency treatment of pediatric casualties by HEMS was evaluated at a helicopter base. Children up to 14 years who were treated by HEMS emergency physicians from Christophorus-1 during primary missions in the alpine region were retrospectively enrolled. RESULTS: Of the 1314 HEMS operations conducted during a 2-year investigation period, pediatric emergencies accounted for 114 (8.7%). Trauma was the most common emergency indication (91.3%) in alpine areas, and 77.5% of the indications were related to skiing and snowboarding; 11.3% of the prehospital pediatric emergencies were classified as life-threatening. Interventions on site were rendered in 46.3% of cases. Mean and SD intervals for approach were 11.0 +/- 3.0 minutes; for treatment, 14.0 +/- 6.0 minutes; and for transport, 8.0 +/- 4.0 minutes. Intervals on site were significantly longer whenever it was necessary to search for an interim landing place (P < .001) or perform rope extrication (P < .001). Aggravating environmental conditions such as low temperature (78.8%), rocky terrain (18.8%), or precipitation (12.5%) were common. CONCLUSIONS: Rapid procedures are preferred to sustained on-scene treatment, particularly when surrounding conditions are hostile. HEMS emergency physicians attempt to keep on-site intervals short and treatment and monitoring to the essential to minimize delay in rescue. PMID- 27377921 TI - Anthropometric adjustments are helpful in the interpretation of BMD and BMC Z scores of pediatric patients with Prader-Willi syndrome. AB - : Anthropometric adjustments of bone measurements are necessary in Prader-Willi syndrome patients to correctly assess the bone status of these patients. This enables physicians to get a more accurate diagnosis of normal versus abnormal bone, allow for early and effective intervention, and achieve better therapeutic results. INTRODUCTION: Bone mineral density (BMD) is decreased in patients with Prader-Willi syndrome (PWS). Because of largely abnormal body height and weight, traditional BMD Z-scores may not provide accurate information in this patient group. The goal of the study was to assess a cohort of individuals with PWS and characterize the development of low bone density based on two adjustment models applied to a dataset of BMD and bone mineral content (BMC) from dual-energy X-ray absorptiometry (DXA) measurements. METHODS: Fifty-four individuals, aged 5-20 years with genetically confirmed PWS, underwent DXA scans of spine and hip. Thirty-one of them also underwent total body scans. Standard Z-scores were calculated for BMD and BMC of spine and total hip based on race, sex, and age for all patients, as well as of whole body and whole-body less head for those patients with total-body scans. Additional Z-scores were generated based on anthropometric adjustments using weight, height, and percentage body fat and a second model using only weight and height in addition to race, sex, and age. RESULTS: As many PWS patients have abnormal anthropometrics, addition of explanatory variables weight, height, and fat resulted in different bone classifications for many patients. Thus, 25-70 % of overweight patients, previously diagnosed as normal, were subsequently diagnosed as below normal, and 40-60 % of patients with below-normal body height changed from below normal to normal depending on bone parameter. CONCLUSIONS: This is the first study to include anthropometric adjustments into the interpretation of BMD and BMC in children and adolescents with PWS. This enables physicians to get a more accurate diagnosis of normal versus abnormal BMD and BMC and allows for early and effective intervention. PMID- 27377922 TI - Pazopanib as a second-line treatment for non-cytokine-treated metastatic renal cell carcinoma: a meta-analysis of the effect of treatment. AB - BACKGROUND: The currently recommended treatment algorithm for patients with advanced renal cell carcinoma who fail the first-line targeted therapy does not normally include pazopanib as a second-line treatment option. It would therefore be of interest to determine the efficiency of pazopanib in this setting in terms of the partial response rate (PRR), disease control rate (DCR), and progression free survival (PFS). METHODS: Peer-reviewed clinical reports without language restriction, both full papers and conference abstracts, which assessed the second line use of pazopanib following failure of first-line non-cytokine-targeted therapy, were included. After the literature retrieval, we conducted a Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-compliant systematic review of the literature and meta-analysis of the size of the effect of each outcome measure (PRR, DCR, and PFS). The effect size and 95 % confidence interval (CI) were calculated using fixed-effect or random-effects models based on the heterogeneity represented by I(2) of selected studies. Meta-analysis forest plots with a fixed-effect model showing the PRR and DCR were created. RESULTS: Our results show that there are no available comparative studies on pazopanib second-line treatment. Only phase II trials or retrospective analysis reports were retrievable. Six studies (comprising 217 patients) were included in the qualitative and quantitative analysis. Pazopanib as a second-line treatment resulted in a PRR of 23 % (95 % CI, 17-31 %; I(2) = 52.6 %) and a DCR of 73 % (95 % CI, 65-80 %; I(2) = 0.00 %). The meta-analysis with fixed-effect model revealed that PFS was 6.5 months (95 % CI, 5.6-7.5 months; I(2) = 86.2 %). CONCLUSIONS: In conclusion, the effectiveness and indication of pazopanib for use in the second line setting has not yet been examined in-depth; however, this meta-analysis has shown that the treatment effects in terms of PRR, DCR, and PFS may be similar to other well-studied second-line targeted therapies. Rigorous comparative phase III trials testing this hypothesis are required. PMID- 27377925 TI - Transposable elements: The enemies within. AB - Understanding transformation mechanisms other than genetic aberrations has recently captured the attention of cancer researchers. To date, the role of transposable elements (TEs) in tumor development remains largely undefined. However, an increasing number of studies have reported that loss of epigenetic control causes TE reactivation and consequent oncogenic transcription. Here, we discuss principal examples of TEs-driven oncogenesis. Available data suggest that long terminal repeats and long interspersed nuclear elements play a pivotal role as alternative promoters. These findings provide definitive experimental evidence that repetitive elements are a powerful underestimated force toward oncogenesis and open the possibility to new therapeutic treatments. PMID- 27377924 TI - Transanal total mesorectal excision (taTME) for rectal cancer: a systematic review and meta-analysis of oncological and perioperative outcomes compared with laparoscopic total mesorectal excision. AB - BACKGROUND: Transanal total mesorectal excision (taTME) is an emerging surgical technique for rectal cancer. However, the oncological and perioperative outcomes are controversial when compared with conventional laparoscopic total mesorectal excision (laTME). METHODS: A systematic review and meta-analysis based on Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was conducted in PubMed, Embase and Cochrane database. All original studies published in English that compared taTME with laTME were included for critical appraisal and meta-analysis. Data synthesis and statistical analysis were carried out using RevMan 5.3 software. RESULTS: A total of seven studies including 573 patients (taTME group = 270; laTME group = 303) were included in our meta-analysis. Concerning the oncological outcomes, no differences were observed in harvested lymph nodes, distal resection margin (DRM) and positive DRM between the two groups. However, the taTME group showed a higher rate of achievement of complete grading of mesorectal quality (OR = 1.75, 95% CI = 1.02 3.01, P = 0.04), a longer circumferential resection margin (CRM) and less involvement of positive CRM (CRM: WMD = 0.96, 95% CI = 0.60-1.31, P <0.01; positive CRM: OR = 0.39, 95% CI = 0.17-0.86, P = 0.02). Concerning the perioperative outcomes, the results for hospital stay, intraoperative complications and readmission were comparable between the two groups. However, the taTME group showed shorter operation times (WMD = -23.45, 95% CI = -37.43 to 9.46, P <0.01), a lower rate of conversion (OR = 0.29, 95% CI = 0.11-0.81, P = 0.02) and a higher rate of mobilization of the splenic flexure (OR = 2.34, 95% CI = 0.99-5.54, P = 0.05). Although the incidence of anastomotic leakage, ileus and urinary morbidity showed no difference between the groups, a significantly lower rate of overall postoperative complications (OR = 0.65, 95% CI = 0.45-0.95, P = 0.03) was observed in the taTME group. CONCLUSIONS: In comparison with laTME, taTME seems to achieve comparable technical success with acceptable oncologic and perioperative outcomes. However, multicenter randomized controlled trials are required to further evaluate the efficacy and safety of taTME. PMID- 27377923 TI - Radiotherapy for Hepatocellular Carcinoma: New Indications and Directions for Future Study. AB - Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide; its incidence is increasing in the United States. Depending on disease extent and underlying liver status, patients may be treated with local, locoregional, and/or systemic therapy. Recent data indicates that radiotherapy (RT) can play a meaningful role in the management of HCC. Here, we review published experiences using RT for HCC, including the use of radiosensitizers and stereotactic RT. We discuss methods for performing preclinical studies of RT for HCC and biomarkers of response. As a part of the HCC Working Group, an informal committee of the National Cancer Institute's Radiation Research Program, we suggest how RT should be implemented in the management of HCC and identify future directions for the study of RT in HCC. PMID- 27377927 TI - Seasonal pattern of Echinococcus re-infection in owned dogs in Tibetan communities of Sichuan, China and its implications for control. AB - BACKGROUND: Human cystic echinococcosis (CE) and alveolar echinococcosis (AE) are highly endemic in Tibetan communities of Sichuan Province. Previous research in the region indicated that domestic dog was the major source of human infection, and observations indicated that domestic dog could have more access to intermediate hosts of Echinococcus spp.: both domestic livestock (CE) viscera and small mammals (AE), in early winter and again in spring. We hypothesized that there would therefore be a significant increase in the risk of canine infection with Echinococcus spp. in these two seasons and conducted a reinfection study to investigate this further. METHODS: Faecal samples were collected from owned dogs in seven townships in Ganze Tibetan Autonomous Prefecture (Sichuan Province, China), and Echinococcus spp. infection status was determined using copro-antigen ELISA. Dogs were sampled in April (spring), July (early summer), September/October (autumn/early winter) and December (winter) in 2009; and in April (spring) 2010. Dogs were treated with praziquantel following each of the five sample collections to eliminate any tapeworms. Information on dog sex, age and body weight was also collected. The t-test, Fisher's exact test, Poisson regression and logistic regression were used to compare means and prevalences, and to identify factors associated with infection status. RESULTS: The proportion of female dogs was significantly lower than that of male dogs; female dogs had significantly higher (22.78 %) baseline copro-ELISA prevalence than males (11.88 %). Dog body weight, sex, age, county and previous infection status at any sampling point had no influence on the re-infection prevalence in general. Poisson regression did not found a significant influence on the re-infection prevalence due to different deworming/sampling time spans. Dogs exhibited significantly higher re-infection prevalences in spring and early summer of 2009 and in early winter between September/October and December of 2009, suggesting a higher infection pressure in these seasons comparing with other seasons. CONCLUSION: Following praziquantel treatment, dog body weight, sex, age, county, deworming time span and previous infection status at any sampling point had no influence on the re-infection prevalence in the region in general. The differences between re-infection prevalences were probably due to the seasonality in Echinoccocus spp. infection pressure in the region. Early winter, spring and early summer should be important seasons for optimal dog deworming intervention in these Tibetan communities. PMID- 27377928 TI - Quality of Life, Integrative Community Therapy, Family Support, and Satisfaction with Health Services Among Elderly Adults with and without Symptoms of Depression. AB - The aim of this cross-sectional study was to analyse quality of life, socio demographic characteristics, family support, satisfaction with health services, and effect of integrative community therapy among non-institutionalised elderly adults with and without symptoms of depression in the state of Rio Grande do Norte, Brazil. Data from elderly adults with (n = 59) and without (n = 61) depressive symptoms were compared. The instruments used were the Mini-Mental State Examination, the short version of the Geriatric Depression Scale, a clinical socio-demographic questionnaire, the abbreviated version of the World Health Organisation Quality of Life questionnaire, the Family Assessment Device, and the Patient Satisfaction with Mental Health Services Rating Scale. Elderly adults with depressive symptoms had lower quality of life in the social relations domain than did those without depressive symptoms (p = 0.003). In addition, compared with those without depression, fewer elderly adults with depressive symptoms attended integrative community therapy (p = 0.04); they also reported a low degree of family involvement in problem solving (p = 0.04) and showed apathy regarding their satisfaction with health services (p = 0.007). These results have important implications in the decision-making process with regard to strategies for improving the health status of elderly adults with depressive symptoms. PMID- 27377926 TI - Recombinant ArtinM activates mast cells. AB - BACKGROUND: Mast cells are hematopoietically derived cells that play a role in inflammatory processes such as allergy, as well as in the immune response against pathogens by the selective and rapid release of preformed and lipid mediators, and the delayed release of cytokines. The native homotetrameric lectin ArtinM, a D-mannose binding lectin purified from Artocarpus heterophyllus seeds, is one of several lectins that are able to activate mast cells. Besides activating mast cells, ArtinM has been shown to affect several biological responses, including immunomodulation and acceleration of wound healing. Because of the potential pharmacological application of ArtinM, a recombinant ArtinM (rArtinM) was produced in Escherichia coli. The current study evaluated the ability of rArtinM to induce mast cell degranulation and activation. RESULTS: The glycan binding specificity of rArtinM was similar to that of jArtinM. rArtinM, via its CRD, was able to degranulate, releasing beta-hexosaminidase and TNF-alpha, and to promote morphological changes on the mast cell surface. Moreover, rArtinM induced the release of the newly-synthesized mediator, IL-4. rArtinM does not have a co stimulatory effect on the FcepsilonRI degranulation via. The IgE-dependent mast cell activation triggered by rArtinM seems to be dependent on NFkB activation. CONCLUSIONS: The lectin rArtinM has the ability to activate and degranulate mast cells via their CRDs. The present study indicates that rArtinM is a suitable substitute for the native form, jArtinM, and that rArtinM may serve as an important and reliable pharmacological agent. PMID- 27377931 TI - Editorial: Professorial Leadership and the h-index: the rights and wrongs of academic nursing. PMID- 27377929 TI - Colonization of CF patients' upper airways with S. aureus contributes more decisively to upper airway inflammation than P. aeruginosa. AB - In cystic fibrosis (CF) patients' airways, inflammatory processes decisively contribute to remodeling and pulmonary destruction. The aims of this study were to compare upper airway (UAW) inflammation in the context of Staphylococcus aureus and Pseudomonas aeruginosa colonization in a longitudinal setting, and to examine further factors influencing UAW inflammation. Therefore, we analyzed soluble inflammatory mediators in noninvasively obtained nasal lavage (NL) of CF patients together with microbiology, medication, and relevant clinical parameters. NL, applying 10 mL of isotonic saline per nostril, was serially performed in 74 CF patients (326 samples). Concentrations of the inflammatory mediators' interleukin (IL)-1beta, IL-6, IL-8, matrix metalloproteinase (MMP)-9, and its anti-protease TIMP-1 were quantified by bead-based multiplexed assay, neutrophil elastase (NE) via ELISA. Culture-based microbiology of the upper and lower airways (LAW), as well as serological and clinical findings, were compiled. Our results indicate that UAW colonization with S. aureus significantly impacts the concentration of all measured inflammatory mediators in NL fluid except TIMP 1, whereas these effects were not significant for P. aeruginosa. Patients with S. aureus colonization of both the UAW and LAW showed significantly increased concentrations of IL-1beta, IL-6, IL-8, MMP-9, and slightly elevated concentrations of NE in NL fluid compared to non-colonized patients. This work elaborates a survey on S. aureus' virulence factors that may contribute to this underestimated pathology. Serial assessment of epithelial lining fluid by NL reveals that colonization of the UAW with S. aureus contributes more to CF airway inflammatory processes than hitherto expected. PMID- 27377930 TI - Functional link between ferroxidase activity of ceruloplasmin and protective effect of apo-lactoferrin: studying rats kept on a silver chloride diet. AB - Strongly pronounced argyrosis caused by adding AgCl to the feed of laboratory rats efficiently mimics the deficiency of ceruloplasmin (CP) ferroxidase activity. Bringing the concentration of AgCl in the feedstuff of lactating rats to 250 mg % and keeping their progeny (Ag-rats) for 3 months on the same silver containing feed provided the serum iron content 1.4 times lower than that in the control group. Besides, the ferroxidase activity of CP dropped to zero. In CP purified from sera of Ag-rats two copper ions were substituted with two silver ions. Using rat models of both post-hemorrhagic and hemolytic anemia we showed that the deficiency of CP ferroxidase activity in Ag-rats affects the iron content in serum, though does not prevent the recovery of hemoglobin level accompanied by exhaustion of iron caches in liver and spleen. When apo lactoferrin (apo-LF) was administered to Ag-rats suffering from either post hemorrhagic or hemolytic anemia, both hemoglobin and serum iron were restored more rapidly than in the control animals. In independent experiments Ag-rats were compared with those fed on regular diet and the former displayed a prolonged 3 day stabilization of hypoxia-inducible factors 1 and 2 alpha (HIF-1a and HIF-2a) along with an increased serum concentration of erythropoietin. Introduction to Ag rats of active CP separately or together with apo-LF reduced that effect to 1 day only. It is concluded that saturation of apo-LF with iron, provided by active CP, can strongly affect its protective capacity. PMID- 27377932 TI - Early prediction of maxillary canine impaction: number doubts. PMID- 27377934 TI - Physician presence at out-of-hospital cardiac arrest is not necessarily the cause of improved survival. AB - A recent publication Hiltunen et al. on Out-of-Hospital Cardiac Arrest (OHCA) in Finland show increased survival when a physician attends an OHCA, compared to EMS. But it is likely that physicians attend OHCA patients with a different prognosis due to comorbidity or illness severity, which causes confounding by indication and is the likely cause for the physician and survival association. PMID- 27377933 TI - ApoA-I induces S1P release from endothelial cells through ABCA1 and SR-BI in a positive feedback manner. AB - Sphingosine-1-phosphate (S1P), which has emerged as a pivotal signaling mediator that participates in the regulation of multiple cellular processes, is derived from various cells, including vascular endothelial cells. S1P accumulates in lipoproteins, especially HDL, and the majority of free plasma S1P is bound to HDL. We hypothesized that HDL-associated S1P is released through mechanisms associated with the HDL maturation process. ApoA-I, a major HDL apolipoprotein, is a critical factor for nascent HDL formation and lipid trafficking via ABCA1. Moreover, apoA-I is capable of promoting bidirectional lipid movement through SR BI. In the present study, we confirmed that apoA-I can facilitate the production and release of S1P by HUVECs. Furthermore, we demonstrated that ERK1/2 and SphK activation induced by apoA-I is involved in the release of S1P from HUVECs. Inhibitor and siRNA experiments showed that ABCA1 and SR-BI are required for S1P release and ERK1/2 phosphorylation induced by apoA-I. However, the effects triggered by apoA-I were not suppressed by inhibiting ABCA1/JAK2 or the SR-BI/Src pathway. S1P released due to apoA-I activation can stimulate the (ERK1/2)/SphK1 pathway through S1PR (S1P receptor) 1/3. These results indicated that apoA-I not only promotes S1P release through ABCA1 and SR-BI but also indirectly activates the (ERK1/2)/SphK1 pathway by releasing S1P to trigger their receptors. In conclusion, we suggest that release of S1P induced by apoA-I from endothelial cells through ABCA1 and SR-BI is a self-positive-feedback process: apoA-I-(ABCA1 and SR-BI)-(S1P release)-S1PR-ERK1/2-SphK1-(S1P production)-(more S1P release induced by apoA-I). PMID- 27377935 TI - Patient with disseminated tuberculosis and rare perianal involvement. PMID- 27377936 TI - Nicotinamide: New Indications in Dermatology. PMID- 27377937 TI - Treatment of Bowen Disease With Photodynamic Therapy and the Advantages of Sequential Topical Imiquimod. AB - Photodynamic therapy (PDT) has been shown to be useful and effective in the treatment of actinic keratosis, Bowen disease, and basal cell carcinoma. We present a series of 13 Bowen disease lesions treated using PDT. Complete responses were achieved in 11 (84%) of the lesions after 3 months of treatment; at 18 months, complete responses were seen in 9 (70%) of the lesions. Patients who presented a partial response or recurrence were treated with topical 5% imiquimod and achieved complete responses. The lesions that presented partial response or recurrence were the largest lesions, between 3 and 5cm in diameter. PDT in monotherapy or combined sequentially with imiquimod is an excellent and well-tolerated therapeutic option for Bowen disease. The treatment has few adverse effects and shows satisfactory results, particularly in multiple large lesions in areas of difficult surgical reconstruction or in elderly patients with a high surgical risk. PMID- 27377938 TI - Current Challenges of Geriatric Voiding Dysfunction in South Korea. PMID- 27377939 TI - Research on Novel Intravesical Drug Delivery Devices. PMID- 27377940 TI - Overview of the Epidemiology of Lower Urinary Tract Dysfunction in South Korea. AB - This review assessed the epidemiology of voiding dysfunctions in South Korea. Comprehensive understanding of this epidemiology is crucial because the senior population and the social burden are increasing because of voiding dysfunctions is growing. We searched the medical records using several terms related to voiding dysfunction: benign prostatic hyperplasia, urinary incontinence, lower urinary tract symptoms, overactive bladder, and nocturia. We then estimated the prevalence of voiding dysfunctions in South Korea; our data were comparable with those from other countries, with slight differences. The ranges of incidences varied widely between studies, mostly because investigators defined disorders differently. Voiding dysfunction greatly affects healthcare costs and individual quality of life; therefore, more proper and valuable epidemiologic data are needed. In addition, efforts to unify the definitions of various voiding dysfunctions and progress in investigational methodologies using multimedia are warranted. PMID- 27377941 TI - Implantable Devices for Sustained, Intravesical Drug Delivery. AB - In clinical settings, intravesical instillation of a drug bolus is often performed for the treatment of bladder diseases. However, it requires repeated instillations to extend drug efficacy, which may result in poor patient compliance. To alleviate this challenge, implantable devices have been developed for the purpose of sustained, intravesical drug delivery. In this review, we briefly summarize the current trend in the development of intravesical drug delivery devices. We also introduce the most recently developed devices with strong potential for intravesical drug-delivery applications. PMID- 27377942 TI - Pentoxifylline Alleviates Perinatal Hypoxic-Ischemia-Induced Short-term Memory Impairment by Suppressing Apoptosis in the Hippocampus of Rat Pups. AB - PURPOSE: Perinatal hypoxic-ischemic brain damage is a major cause of acute mortality and chronic neurologic morbidity in infants and children. We investigated the effects of pentoxifylline, a methylxanthine derivative and type 4 phosphodiesterase inhibitor, on short-term memory and apoptotic neuronal cell death in the hippocampus following perinatal hypoxic-ischemia in newborn rats. METHODS: We used a step-down avoidance task to evaluate short-term memory and 3' 5'-cyclic adenosine monophosphate (cAMP) assay to detect cAMP levels. We evaluated apoptosis using a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay for evidence of DNA fragmentation, immunohistochemistry for caspase-3 levels, and western blot for Bcl-2 and Bax. RESULTS: Perinatal hypoxic-ischemic injury increased apoptotic cell death in the hippocampus, resulting in impaired short-term memory with decreased cAMP levels. Pentoxifylline treatment improved short-term memory by suppressing apoptotic cell death in the hippocampus with elevated cAMP levels. CONCLUSIONS: Pentoxifylline ameliorated perinatal hypoxic-ischemia in rat pups. This alleviating effect could be ascribed to the inhibition apoptosis due to increased cAMP production by pentoxifylline. PMID- 27377943 TI - Anti-interleukin-33 Reduces Ovalbumin-Induced Nephrotoxicity and Expression of Kidney Injury Molecule-1. AB - PURPOSE: To evaluate the effect of anti-interleukin-33 (anti-IL-33) on a mouse model of ovalbumin (OVA)-induced acute kidney injury (AKI). METHODS: Twenty-four female BALB/c mice were assigned to 4 groups: group A (control, n=6) was administered sterile saline intraperitoneally (i.p.) and intranasally (i.n.); group B (allergic, n=6) was administered i.p./i.n. OVA challenge; group C (null treatment, n=6) was administered control IgG i.p. before OVA challenge; and group D (anti-IL-33, n=6) was pretreated with 3.6 ug of anti-IL-33 i.p. before every OVA challenge. The following were evaluated after sacrifice: serum blood urea nitrogen and creatinine levels, Kidney injury molecule-1 gene (Kim-1) and protein (KIM-1) expression in renal parenchyma, and expression of cyclooxygenase-2 (COX 2), inducible nitric oxide synthase (iNOS), phosphorylated endothelial NOS (p eNOS), and phosphorylated AMP kinase (p-AMPK) proteins in renal parenchyma. RESULTS: After OVA injection and intranasal challenge, mice in groups B and C showed significant increases in the expression of Kim-1 at both the mRNA and protein levels. After anti-IL-33 treatment, mice in group D showed significant Kim-1 down-regulation at the mRNA and protein levels. Group D also showed significantly lower COX-2 protein expression, marginally lesser iNOS expression than groups B and C, and p-eNOS and p-AMPK expression at baseline levels. CONCLUSIONS: Kim-1 could be a useful marker for detecting early-stage renal injury in mouse models of OVA-induced AKI. Further, anti-IL-33 might have beneficial effects on these mouse models. PMID- 27377945 TI - Incidence of Nitrituria and Its Association With Metabolic Syndrome: Results From the Korean National Health and Nutrition Examination Survey V (2010-2012). AB - PURPOSE: To investigate the incidence of nitrituria and the relationship between nitrituria and metabolic syndrome (MetS). METHODS: Data from the Korean National Health and Nutrition Examination Survey V were used. A total of 19,083 participants were included. The chi-square test, the Mantel-Haenszel extension, logistic regression analysis, and multiple linear regression were used to analyze the data. RESULTS: A total of 2.0% of the participants had nitrituria. The incidence of nitrituria significantly increased with age (P trend<0.001). In addition, nitrituria in women began to significantly increase in the fifth decade, more than in men, and this difference was maintained in the 60s, 70s, and greater than 70s age groups (P<0.001). After adjusting for confounders, the odds ratio (OR) for nitrituria in the MetS group was significantly increased, as compared to the OR for nitrituria in the group without MetS (MetS: OR, 1.577; 95% confidence interval [CI], 1.134-2.192; P=0.007). The glycosylated hemoglobin of the nitrite positive group was significantly higher than the negative group (adjusted mean +/-standard error: 6.108 +/-0.081 vs. 5.883+/-0.065, P<0.001). CONCLUSIONS: An effective health policy for urinary tract infection (UTI) is needed for older age groups and women. Screening or management guidelines for UTI are needed in MetS patients. PMID- 27377944 TI - Increased Expression of Herpes Virus-Encoded hsv1-miR-H18 and hsv2-miR-H9-5p in Cancer-Containing Prostate Tissue Compared to That in Benign Prostate Hyperplasia Tissue. AB - PURPOSE: Previously, we reported the presence of virus-encoded microRNAs (miRNAs) in the urine of prostate cancer (CaP) patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. METHODS: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH), 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR) and immunocytochemistry using nanoparticles as molecular beacons. RESULTS: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001). Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9). CONCLUSIONS: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections. PMID- 27377946 TI - Association of Functional Ability and Benign Prostatic Hyperplasia With Urinary Incontinence in Older Korean Men. AB - PURPOSE: The purpose of this study was to determine the prevalence of urinary incontinence (UI) and analyze its association with instrumental activities of daily living (IADL) and benign prostatic hyperplasia (BPH) in community-dwelling older men in Korea. METHODS: This study was a secondary analysis of data from the Actual Living Condition of the Elderly and Welfare Need Survey conducted in the year 2008. Data was subjected to hierarchical logistic regression analysis to examine the association of IADL and BPH with UI in older men, entering IADL and BPH in model 1, and age, body mass index (BMI) and education in model 2, and then comorbidities and walking speed in model 3. RESULTS: Of 6,185 men, 243 (3.9%) had self-reported UI. The prevalence of UI was 1.8% in men aged 60-64 years and 11.7% in those aged 85 years and above, indicating an increase in the prevalence of UI with their age. IADL and BPH remained the only significant factors associated with UI in model 1 (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.44 1.64 and OR, 2.73; 95% CI, 1.47-5.10, respectively), model 2 (OR, 1.50; 95% CI, 1.40-1.61 and OR, 2.68; 95% CI, 1.42-5.07), and model 3 (OR, 1.43; 95% CI, 1.32 1.54 and OR, 2.58; 95% CI, 1.36-4.90). CONCLUSIONS: IADL limitations and presence of BPH were associated with UI in older men after controlling for BMI, education, comorbidities, and walking speed. Thus, UI should be assessed in older Korean men with IADL decline and BPH. Gender-sensitive interventions to attenuate IADL limitations and manage BPH should be developed and applied to improve UI in older men. PMID- 27377947 TI - Holmium Laser Enucleation of the Prostate is Safe for Patients Above 80 Years: A Prospective Study. AB - PURPOSE: To evaluate the effect of age on the efficacy and safety of holmium laser enucleation of the prostate (HoLEP) for the treatment of symptomatic benign prostatic hyperplasia (BPH). METHODS: A total of 579 patients underwent HoLEP procedure performed by a single surgeon (SJO) between December 2009 and May 2013. The perioperative and functional outcomes of patients in the age groups of 50-59 (group A, n=44), 60-69 (group B, n=253), 70-79 (group C, n=244), and >=80 years (group D, n=38) were compared. The Clavien-Dindo system was used to evaluate clinical outcomes. The International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), postvoid residual (PVR) urine volume, and urinary continence were used to assess functional outcomes. RESULTS: In this study, the patients >=80 years had significantly higher presence of hypertension (P=0.007), total prostate volumes (P=0.024), transitional zone volume (P=0.002), American Society of Anesthesiologists scores (P=0.006), urinary retention (P=0.032), and anticoagulation use (P=0.008) at preoperative period. Moreover, the mean values of operation time, enucleation time, morcellation time, and enucleation weight were higher in group D compared with other group patients (P=0.002, P=0.010, P<0.01, and P=0.009, respectively). Patients aged >=80 years had a longer hospital stay time (2.9+/-1.8 days) than other groups (group A, 2.3+/-0.7 days; group B, 2.3+/-0.7 days vs. group C, 2.4+/-0.7 days; P=0.001). All groups were similar in regard to the incidence of complications (Clavien-Dindo grade) post operatively (P>0.05). All the patients in the present study showed improvement in functional outcomes after HoLEP. By the sixth month, there were no significant differences in IPSS, quality of life, Qmax, and PVR among the groups (P>0.05). CONCLUSIONS: Compared with younger patients, the patients aged >=80 years had a similar overall morbidity and 6-month functional outcomes of HoLEP. HoLEP is a safe and effective treatment for BPH among the elderly. PMID- 27377948 TI - Prevalence of Spina Bifida Occulta and Its Relationship With Overactive Bladder in Middle-Aged and Elderly Chinese People. AB - PURPOSE: To investigate the prevalence of spina bifida occulta (SBO) and its relationship with the presence of overactive bladder (OAB) in middle-aged and elderly people in China. METHODS: A cross-sectional community-based survey was carried out at 7 communities in Zhengzhou City, China from December 15, 2013 to June 10, 2014, where residents aged over 40 years were randomly selected to participate. All of the participants underwent lumbosacral radiographic analysis and relevant laboratory tests. A questionnaire including basic information, past medical history and present illness, and the OAB symptom score was filled out by all participants. Chi-square tests and logistic regression were used for data analysis with a P-value of <0.05 denoting statistical significance. RESULTS: A total of 1,061 subjects were qualified for the final statistical analysis (58.8+/ 11.7 years; male, 471 [44.4%]; female, 590 [55.6%]). The overall prevalence of SBO was 15.1% (160 of 1,061): 18.3% (86 of 471) in men and 12.5% (74 of 590) in women. Among these subjects, 13.7% (145 of 1,061) had OAB: 13.2% (62 of 471) in men and 14.1% (83 of 590) in women. The results of logistic regression showed that age, SBO, history of cerebral infarction (HCI), and constipation were risk factors for OAB (P<0.05), while sex, history of childhood enuresis (HCE), body mass index (BMI), and diabetes mellitus (DM) were not (P>0.05). In men, age, SBO, and constipation were risk factors for OAB (P<0.05), while HCE, BMI, DM, HCI, and benign prostate hyperplasia were not (P>0.05). In women, age, SBO, and HCI were risk factors for OAB (P<0.05), while HCE, BMI, DM, vaginal delivery, and constipation were not (P>0.05). CONCLUSIONS: The prevalence of SBO is high and it is related to OAB in middle-aged and elderly people in China. PMID- 27377949 TI - Reliability and Validity of the Turkish Language Version of the International Consultation on Incontinence Questionnaire - Male Lower Urinary Tract Symptoms. AB - PURPOSE: Patients receiving treatment for benign prostate hyperplasia may have persistent storage symptoms. There has been increasing debate on the precision and accuracy of the International Prostate Symptom Score questionnaires over other questionnaires in evaluating all the complaints of lower urinary tract symptoms (LUTS). The aim of this study was to perform the validity and reliability analysis of the Turkish version of the Internatinal Consultation on Incontinence Questionnaire-Male LUTS (ICIQ-MLUTS). METHODS: Linguistic validation was studied (i.e., translation and back translation). Intelligibility was completed between October 2013 and November 2013. Data was collected between November 2013 and March 2014. The stability and reliability of the form were measured with the Cronbach test. RESULTS: In total, 117 male patients were included in the study. At the first visit, the mean age of the patients was 59 years (range, 18-84 years). For reliability, the Cronbach alpha value was 0.798, demonstrating the internal consistency of the form (r>0.7). The internal consistency of each question was examined separately and found to be over 0.7. For the evaluation of test-retest reliability, the test was administered to 116 patients for a second time with an interval of 2-4 weeks. The first and second test scores for each question were found to be correlated (r=0.741). CONCLUSIONS: ICIQ-MLUTS is a new questionnaire, which can be used for evaluating male LUTS in Turkey. We believe that the Turkish version of the ICIQ-MLUTS is an important breakthrough in our country. PMID- 27377950 TI - Electroanatomical Mapping of the Urinary Bladder. AB - A noncontact mapping system (EnSite) was used for electroanatomical mapping of the bladder simultaneously with pressure flow study in three women with lower urinary tract symptoms. We selected the periods of obvious detrusor activity. Data were processed to remove baseline drift, and an envelope of electrovesicography (EVG) data was created. The correlation coefficient for the correlation between between the EVG envelope and the detrusor pressure (Pdet) was calculated. Bladder geometry was successfully created in all 3 patients. Simultaneous recording of EVG and pressure flow data was successful in 1 patient. Scatter plots were made of the highest correlation coefficient, showing a positive correlation between the Pdet and the envelope, and negative correlation between abdominal pressure (Pabd) and the envelope. Minimal electrical activity could be observed. Significant weak to moderate correlation coefficients were found for the correlations between Pdet and EVG and between Pabd and EVG. PMID- 27377951 TI - Erratum: Extracellular Matrix Revisited: Roles in Tissue Engineering. AB - [This corrects the article on p. S23 in vol. 20, PMID: 27230457.]. PMID- 27377952 TI - How obesity relates to socio-economic status: identification of eating behavior mediators. AB - BACKGROUND: Socio-economic status (SES) is a strong determinant of eating behavior and the obesity risk. OBJECTIVE: To determine which eating and lifestyle behaviors mediate the association between SES and obesity. METHODS: We performed a case-control study of 318 obese people and 371 non-obese people in northern France. Ten eating behavior traits were assessed using the Three-Factor Eating Questionnaire Revised 21-Item and an eating attitude questionnaire (on plate size, the number of servings, reasons for stopping eating and the frequency of eating standing up, eating in front of the television set (TV) and eating at night). The SES score (in three categories) was based on occupation, education and income categories. Mediation analysis was performed using the test of joint significance and the difference of coefficients test. RESULTS: The age- and gender-adjusted obesity risk was higher for individuals in the low-SES groups (odds ratio (OR) (95% confidence interval (CI)=1.82 (1.48-2.24), P<0.0001). Additional servings were associated with a higher obesity risk (OR=3.43, P<0.0001). Cognitive restraint (P<0.0001) and emotional eating (P<0.0001) scores were higher in obese participants than in non-obese participants but did not depend on SES. Of the 10 potential factors tested, eating off a large plate (P=0.01), eating at night (P=0.04) and uncontrolled eating (P=0.03) significantly mediated the relationship between SES and obesity. CONCLUSION: Our results highlighted a number of obesogenic behaviors among socially disadvantaged participants: large plate size, uncontrolled eating and eating at night were significant mediators of the relationship between SES and the obesity risk. PMID- 27377953 TI - Dietary luteolin activates browning and thermogenesis in mice through an AMPK/PGC1alpha pathway-mediated mechanism. AB - BACKGROUND: Two brown-like adipocytes, including classical brown adipocytes from brown adipose tissues and beige cells from white adipose tissues, regulate thermogenesis. The developmental and functional induction of brown-like cells provides a defense against obesity and associated metabolic diseases. Our previous study suggests dietary luteolin can improve diet-induced obesity and insulin resistance in mice. Here we further elucidated the action of the natural flavonoid on energy expenditure and adaptive thermogenesis. METHODS: Five-week old male C57BL/6 mice were fed low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with 0.01% luteolin. After 12 weeks, their energy expenditure were detected using a combined indirect calorimetry system. Moreover, thermogenic program and associated molecular regulators were assessed in adipose tissues. In another independent study, even-aged mice were fed LFD and luteolin-containing LFD for 12 weeks, and their energy expenditure and thermogenic program were also investigated. Finally, differentiated primary brown and subcutaneous adipocytes were used to identify the critical participation of AMPK/PGC1alpha signaling in luteolin-regulated browning and thermogenesis. RESULTS: In mice fed either HFD or LFD, dietary luteolin supplement increased oxygen consumption, carbon dioxide production and respiratory exchange ratio. The enhancement in energy expenditure was accompanied by the upregulation of thermogenic genes in brown and subcutaneous adipose tissues. Meanwhile, several important AMPK/PGC1alpha signaling molecules were activated by dietary luteolin in the tissues. Further, luteolin treatment directly elevated thermogenic gene expressions and activated AMPK/PGC1alpha signaling in differentiated primary brown and subcutaneous adipocytes, whereas AMPK inhibitor Compound C reversed the efficiencies. CONCLUSIONS: Dietary luteolin activated browning and thermogenesis through an AMPK/PGC1alpha pathway-mediated mechanism. PMID- 27377955 TI - Divergent Coupling of Alcohols and Amines Catalyzed by Isoelectronic Hydride Mn(I) and Fe(II) PNP Pincer Complexes. AB - Herein, we describe an efficient coupling of alcohols and amines catalyzed by well-defined isoelectronic hydride Mn(I) and Fe(II) complexes, which are stabilized by a PNP ligand based on the 2,6-diaminopyridine scaffold. This reaction is an environmentally benign process implementing inexpensive, earth abundant non-precious metal catalysts, and is based on the acceptorless alcohol dehydrogenation concept. A range of alcohols and amines including both aromatic and aliphatic substrates were efficiently converted in good to excellent isolated yields. Although in the case of Mn selectively imines were obtained, with Fe exclusively monoalkylated amines were formed. These reactions proceed under base free conditions and required the addition of molecular sieves. PMID- 27377954 TI - Interspecies metabolic diversity of harmaline and harmine in in vitro 11 mammalian liver microsomes. AB - The beta-carboline alkaloids harmaline and harmine are widely present in hallucinogenic plants with great potential for treating depression, Parkinson's disease, and Alzheimer's disease. The present study was to elucidate metabolic difference of harmaline and harmine in 11 mammalian liver microsomes in order to quantitate species-specific metabolic profiles. Using the probe substrate reaction, the enzymatic activities for 8 CYP450 isozymes of 11 liver microsomes were characterized. Combining ultra performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q/TOF-MS) and ultra performance liquid chromatography combined with electrospray ionization quadrupole tandem mass spectrometry (UPLC-ESI-MS/MS) methods, 18 metabolites for harmaline and 11 for harmine were identified. The metabolism patterns differences of them presented discrepancy in the quality and quantity of metabolites. It was notable that O-sulfate conjugation was detected in all species except sheep. The intrinsic clearance CLint, LM values for the metabolites harmine and harmol in rabbits (37.5 and 42.4 MUL/min/mg) were higher than those in other animals, while dogs (16.2 and 16.7 MUL/min/mg) and humans (16.0 and 16.3 MUL/min/mg) exhibited similar in vitro metabolic clearance. These observations suggested that harmaline and harmine were rapidly metabolized in liver microsomes of rat, mouse, and rabbit; moderately metabolized in human and dog; while weakly metabolized in sheep. Comprehensive analysis of the metabolism indicated that dogs and humans showed considerable similarity in the elimination of parent drugs, metabolic profiles, and catalytic processes. To summarize, these findings illustrated that in vitro studies of harmaline and harmine metabolic profiles in different species are helpful for the proper selection and interpretation of animal models for pharmacological and toxicological evaluation, and will ultimately provide useful guidance for the development of beta-carboline alkaloids. Copyright (c) 2016 John Wiley & Sons Ltd. PMID- 27377956 TI - Impact of seductive details on the acquisition and transfer of laparoscopic suturing skills: Emotionally interesting or cognitively taxing? AB - BACKGROUND: A common strategy to increase learner engagement is to interweave educational material with interesting but slightly tangential tidbits of information (eg, "war stories" and funny anecdotes), known as seductive details. Our objective was to examine the impact of seductive details on initial acquisition and transfer of basic laparoscopic surgical skills. METHODS: Novices (first- to fourth-year medical students) were randomized into control (N = 47) or seductive details (N = 42) groups. Curricula consisted of a baseline skills assessment (Fundamentals of Laparoscopic Surgery Task 1), instructional video on intracorporeal laparoscopic suturing (Fundamentals of Laparoscopic Surgery Task 5), multiple choice quiz, practice, and assessment on both primary and transfer tasks. Two separate instructional videos were used for Task 5; 20% of the seductive details group's instructional video consisted of seductive details, whereas the control group's video included no seductive details. Participants completed questionnaires of mental workload and task engagement after training. We also conducted a mediation analysis, which is a statistical approach to identify causal paths among a group of variables. RESULTS: Baseline skill scores (control: 112 +/- 52; standard deviation: 118 +/- 56; 0 = lowest possible score; 600 = highest possible score) and knowledge scores (control: 76 +/- 19; standard deviation: 74 +/- 16; 0 = lowest possible score; 100 = highest possible score) were similar for both groups. The control group demonstrated better (higher) performance on both the primary (434 +/- 193 vs 399 +/- 133, P < .05) and transfer (184 +/- 74 vs 149 +/- 91, P < .05) suturing tasks. Mental workload, as measured by the National Aeronautics and Space Administration-Task Load Index, was more demanding (higher) for the seductive details group (3.8 +/- 0.5 vs 3.4 +/- 0.7, P < .01; 1 = low workload; 5 = high workload) and was investigated as the possible mechanism by which group assignment impacted performance. Mediational paths using hierarchical regression were significant (P < .05), suggesting that trainees in the seductive details group performed worse because of their increased workload. CONCLUSION: Our findings suggest that the inclusion of seductive details may be detrimental to the acquisition and transfer of laparoscopic surgical skills due to increased mental workload for trainees. PMID- 27377957 TI - Quantitative LC-MS/MS Glycomic Analysis of Biological Samples Using AminoxyTMT. AB - Protein glycosylation plays an important role in various biological processes, such as modification of protein function, regulation of protein-protein interactions, and control of turnover rates of proteins. Moreover, glycans have been considered as potential biomarkers for many mammalian diseases and development of aberrant glycosylation profiles is an important indicator of the pathology of a disease or cancer. Hence, quantitation is an important aspect of a comprehensive glycomics study. Although numerous MS-based quantitation strategies have been developed in the past several decades, some issues affecting sensitivity and accuracy of quantitation still exist, and the development of more effective quantitation strategies is still required. Aminoxy tandem mass tag (aminoxyTMT) reagents are recently commercialized isobaric tags which enable relative quantitation of up to six different glycan samples simultaneously. In this study, liquid chromatography and mass spectrometry conditions have been optimized to achieve reliable LC-MS/MS quantitative glycomic analysis using aminoxyTMT reagents. Samples were resuspended in 0.2 M sodium chloride solution to promote the formation of sodium adduct precursor ions, which leads to higher MS/MS reporter ion yields. This method was first evaluated with glycans from model glycoproteins and pooled human blood serum samples. The observed variation of reporter ion ratios was generally less than 10% relative to the theoretical ratio. Even for the highly complex minor N-glycans, the variation was still below 15%. This strategy was further applied to the glycomic profiling of N-glycans released from blood serum samples of patients with different esophageal diseases. Our results demonstrate the benefits of utilizing aminoxyTMT reagents for reliable quantitation of biological glycomic samples. PMID- 27377958 TI - TMPRSS2:ERG gene aberrations may provide insight into pT stage in prostate cancer. AB - BACKGROUND: TMPRSS2:ERG gene aberration may be a novel marker that improves risk stratification of prostate cancer before definitive cancer therapy, but studies have been inconclusive. METHODS: The study cohort consisted of 202 operable prostate cancer Slovenian patients who underwent laparoscopic radical prostatectomy. We retrospectively constructed tissue microarrays of their prostatic specimens for fluorescence in situ hybridization, with appropriate signals obtained in 148 patients for subsequent statistical analyses. RESULTS: The following genetic aberrations were found: TMPRSS2:ERG fusion, TMPRSS2 split (a non-ERG translocation) and ERG split (an ERG translocation without involvement of TMPRSS2). TMPRSS2:ERG gene fusion happened in 63 patients (42 %), TMPRSS2 split in 12 patients and ERG split in 8 patients. Association was tested between TMPRSS2:ERG gene fusion and several clinicopathological variables, i.e., pT stage, extended lymph node dissection status, and Gleason score, correcting for multiple comparisons. Only the association with pT stage was significant at p = 0.05: Of 62 patients with pT3 stage, 34 (55 %) had TMPRSS2:ERG gene fusion. In pT3 stage patients, stronger (but not significant) association between eLND status and TMPRSS2:ERG gene fusion was detected. We detected TMPRSS2:ERG gene fusion in 64 % of the pT3 stage patients where we did not perform an extended lymph node dissection. CONCLUSIONS: Our results indicate that it is possible to predict pT3 stage at final histology from TMPRSS2:ERG gene fusion at initial core needle biopsy. FISH determination of TMPRSS2:ERG gene fusion may be particularly useful for patients scheduled to undergo a radical prostatectomy in order to improve oncological and functional results. PMID- 27377960 TI - Corrigendum. PMID- 27377959 TI - Comparison of the miRNA profiles in HPV-positive and HPV-negative tonsillar tumors and a model system of human keratinocyte clones. AB - BACKGROUND: Better insights into the molecular changes involved in virus associated and -independent head and neck cancer may advance our knowledge of HNC carcinogenesis and identify critical disease biomarkers. Here we aimed to characterize the expression profiles in a matched set of well-characterized HPV dependent and HPV-independent tonsillar tumors and equivalent immortalized keratinocyte clones to define potential and clinically relevant biomarkers of HNC of different etiology. METHODS: Fresh frozen tonsillar cancer tissues were analyzed together with non-malignant tonsillar tissues and compared with cervical tumors and normal cervical tissues. Furthermore, relative miRNAs abundance levels of primary and immortalized human keratinocyte clones were evaluated. The global quantitation of miRNA gene abundance was performed using a TaqMan Low Density Array system. The confirmation of differentially expressed miRNAs was performed on a set of formalin-fixed paraffin-embedded tumor samples enriched for the tumor cell fraction by macrodissection. RESULTS: We defined 46 upregulated and 31 downregulated miRNAs characteristic for the HPV-positive tonsillar tumors and 42 upregulated miRNAs and 42 downregulated miRNAs characteristic for HPV-independent tumors. In comparison with the expression profiles in cervical tumors, we defined miR-141-3p, miR-15b-5p, miR-200a-3p, miR-302c-3p, and miR-9-5p as specific for HPV induced malignancies. MiR-335-5p, miR-579-3p, and miR-126-5p were shared by the expression profiles of HPV-positive tonsillar tumors and of the HPV immortalized keratinocyte clones, whereas miR-328-3p, miR-34c-3p, and miR-885-5p were shared by the miRNA profiles of HPV-negative tonsillar tumors and the HPV negative keratinocytes. CONCLUSIONS: We identified the miRNAs characteristic for HPV-induced tumors and tonsillar tumors of different etiology, and the results were compared with those of the model system. Our report presents the basis for further investigations leading to the identification of clinically relevant diagnostic and/or therapeutic biomarkers for tumors of viral and non-viral etiology. PMID- 27377961 TI - Aboriginal and Torres Strait Islander oral health and its impact among adults: A cross-sectional study. AB - BACKGROUND: Robust oral health epidemiological information for Aboriginal and Torres Strait Islander adults is scant. Set within a large urban population, this study describes self-reported oral health behaviours, status and impact assessed through computerized health checks (HC), stratified by age groups and sex, and identifies associations with dental appearance satisfaction. METHODS: This was a cross-sectional study of Aboriginal and Torres Strait Islander adults (aged >=20 years) attending the Southern Queensland Centre of Excellence in Aboriginal and Torres Strait Islander Primary Health Care between 1 January 2014 and 31 December 2015 who had HC and provided research consent. RESULTS: There were 945 patients, 466 (49.3%) female, with an average age of 41.3 years (range, 20-82). Overall, 97.3% owned a toothbrush and 56.2% brushed two or more times/day. Despite self reporting a significant oral health burden, only 28.8% visited a dentist within 12 months, mostly due to problems (84.3%). Surprisingly, only 28.4% reported dental appearance dissatisfaction, likely a result of community normalization whereby people are resigned to poor oral health. CONCLUSIONS: Under-utilization of dental services remains problematic for Aboriginal and Torres Strait Islander adults. To close the oral heath gap, culturally appropriate, acceptable and safe integrated primary health systems, with co-located dental services, demand consideration. PMID- 27377962 TI - The Three Gorges Dam: Does it accelerate or delay the progress towards eliminating transmission of schistosomiasis in China? AB - The Three Gorges Dam, located in the largest endemic area of schistosomiasis in China, is one of the world's largest hydroelectric projects to date. Some large scale hydro projects have resulted in schistosomiasis emergence or re-emergence. Therefore, the dam's potential impact on the transmission of Schistosoma japonicum has raised concerns from medical researchers worldwide. A systematic literature review, coupled with an analysis of data on the water level and snail density in the Yangtze River was conducted to assess the impact of the dam on schistosomiasis transmission after more than 10 years of operation. The dam has significantly altered the water levels in the Yangtze River according to different seasons. These changes directly impact the ecology of the schistosome snail host. Due to the dam, there has been a reduction in the density of Oncomelania snails and/or changes in the distribution of snails. The prevalence of infection with S. japonicum has decreased in the downstream areas of the dam, including in the Dongting and Poyang Lakes. The prevalence of infection with S. japonicum in humans has decreased from 6.80 % in 2002 (before the dam began operating) to 0.50 % in 2012, and the number of people infected with S. japonicum have decreased from 94 208 in 2002 to 59 200 in 2011 in the Poyang Lake region. The presence of the dam does not seem to affect snail breeding or the prevalence of schistosomiasis in the Three Gorges Reservoir. Overall, the Three Gorges Dam has significantly contributed to changes in hydrology after more than 10 years of the dam operating. The changes caused by the dam, together with integrated control of schistosomiasis, might be accelerating the progress towards eliminating the transmission of S. japonicum in the middle and lower reaches of the Yangtze River. Despite the positive effect the dam is having in controlling S. japonicum transmission, continued surveillance is required to monitor the future ecological impacts of the dam over the long term. PMID- 27377964 TI - Alpha-lipoic acid attenuates endoplasmic reticulum stress-induced insulin resistance by improving mitochondrial function in HepG2 cells. AB - Alpha-lipoic acid (ALA) has been reported to have beneficial effects for improving insulin sensitivity. However, the underlying molecular mechanism of the beneficial effects remains poorly understood. Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are considered causal factors that induce insulin resistance. In this study, we investigated the effect of ALA on the modulation of insulin resistance in ER-stressed HepG2 cells, and we explored the potential mechanism of this effect. HepG2 cells were incubated with tunicamycin (Tun) for 6h to establish an ER stress cell model. Tun treatment induced ER stress, mitochondrial dysfunction and insulin resistance. Interestingly, ALA had no significant effect on ER stress signals. Pretreatment of the ER stress cell model with ALA for 24h improved insulin sensitivity, restored the expression levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes and increased intracellular ATP production. Moreover, ALA augmented the beta-oxidation capacity of the mitochondria. Importantly, ALA treatment could decrease oligomycin-induced mitochondrial dysfunction and then improved insulin resistance. Taken together, our data suggest that ALA prevents ER stress-induced insulin resistance by enhancing mitochondrial function. PMID- 27377963 TI - The dual role of FOXF2 in regulation of DNA replication and the epithelial mesenchymal transition in breast cancer progression. AB - Dysregulation of Forkhead-box (FOX) transcription factors is linked to cancers of numerous tissue types. Here, we report that FOXF2 is frequently silenced in luminal-type and HER2-positive breast cancers, but is overexpressed in basal-like breast cancers; thus, FOXF2 appears to play distinct roles in different breast cancer subtypes. Inactivation of FOXF2 in luminal-type and HER2-positive breast cancers is attributable to epigenetic silencing. Silencing of FOXF2 is associated with poor prognosis in luminal-type breast cancer. Ectopic expression of FOXF2 in luminal and HER2-positive breast cancer cells suppresses their tumorigenic properties in vitro and in vivo via inhibition of the CDK2-RB-E2F cascade. The in vivo function of FOXF2 is to maintain the stringency of DNA replication, and its loss triggers dysregulation of DNA replication, which in turn activates the p53 checkpoint pathway. Besides its role in cell cycle regulation, FOXF2 is functionally required for mobility and epithelial-to-mesenchymal transition (EMT) of normal breast epithelial cells. In basal-like breast cancer cells, the cell cycle function of FOXF2 is impaired. However, the EMT function of FOXF2 is still required for mobility, invasiveness and anchorage-independent growth of basal like breast cancer cells. Our gene expression profiling studies demonstrate that FOXF2 regulates the expression of genes implicated in cell cycle and EMT regulation. Moreover, FOXF2 is highly co-expressed with basal- and metastasis related genes in breast cancer. These findings suggest that FOXF2 has a dual role in breast tumorigenesis and functions as either a tumor suppressor or an oncogene depending on the breast tumor subtype. PMID- 27377965 TI - Nuclear translocation of IQGAP1 protein upon exposure to puromycin aminonucleoside in cultured human podocytes: ERK pathway involvement. AB - IQGAP1, a protein that links the actin cytoskeleton to slit diaphragm proteins, is involved in podocyte motility and permeability. Its regulation in glomerular disease is not known. We have exposed human podocytes to puromycin aminonucleoside (PAN), an inducer of nephrotic syndrome in rats, and studied the effects on IQGAP1 biology and function. In human podocytes exposed to PAN, a nuclear translocation of IQGAP1 was observed by immunocytolocalization and confirmed by Western blot after selective nuclear/cytoplasmic extraction. In contrast to IQGAP1, IQGAP2 expression remained cytoplasmic. IQGAP1 nuclear translocation was associated with a significant decrease in its interaction with nephrin and podocalyxin. Activation of the ERK pathway was observed in PAN treated podocytes with a preponderant nuclear localization of the phosphorylated form of ERK (P-ERK). The interaction between IQGAP1 and P-ERK increased upon podocyte exposure to PAN. Inhibitors of ERK pathway activation blocked IQGAP1 nuclear translocation (p<0.02). Chromatin interaction protein assays demonstrated an interaction of IQGAP1 with chromatin and with Histone H3, which increased in response to PAN. In summary, PAN induces the ERK dependent translocation of IQGAP1 into the nuclei in human podocytes which leads to the interaction of IQGAP1 with chromatin and Histone H3, and decreased interactions between IQGAP1 and slit-diaphragm proteins. Therefore, IQGAP1 may have a role in podocyte gene regulation in glomerular disease. PMID- 27377967 TI - What's the Evidence: A Review of the One-Minute Preceptor Model of Clinical Teaching and Implications for Teaching in the Emergency Department. AB - BACKGROUND: The 2012 Academic Emergency Medicine Consensus Conference, "Education Research in Emergency Medicine: Opportunities, Challenges, and Strategies for Success" noted that emergency medicine (EM) educators often rely on theory and tradition in molding their approaches to teaching and learning, and called on the EM education community to advance the teaching of our specialty through the performance and application of research in teaching and assessment methods, cognitive function, and the effects of education interventions. OBJECTIVE: The purpose of this article is to review the research-based evidence for the effectiveness of the one-minute preceptor (OMP) teaching method, and to provide suggestions for its use in clinical teaching and learning in EM. DISCUSSION: This article reviews hypothesis-testing education research related to the use of the OMP as a pedagogical method applicable to clinical teaching. Evidence indicates that the OMP prompts the teaching of higher level concepts, facilitates the assessment of students' knowledge, and prompts the provision of feedback. Students indicate satisfaction with this method of clinical case-based discussion teaching. CONCLUSION: Advancing EM education will require that high quality education research results be translated into actual curricular, pedagogical, assessment, and professional development changes. The OMP is a pedagogical method that is applicable to teaching in the emergency department. PMID- 27377966 TI - Bacterial partition complexes segregate within the volume of the nucleoid. AB - Precise and rapid DNA segregation is required for proper inheritance of genetic material. In most bacteria and archaea, this process is assured by a broadly conserved mitotic-like apparatus in which a NTPase (ParA) displaces the partition complex. Competing observations and models imply starkly different 3D localization patterns of the components of the partition machinery during segregation. Here we use super-resolution microscopies to localize in 3D each component of the segregation apparatus with respect to the bacterial chromosome. We show that Par proteins locate within the nucleoid volume and reveal that proper volumetric localization and segregation of partition complexes requires ATPase and DNA-binding activities of ParA. Finally, we find that the localization patterns of the different components of the partition system highly correlate with dense chromosomal regions. We propose a new mechanism in which the nucleoid provides a scaffold to guide the proper segregation of partition complexes. PMID- 27377968 TI - High-level SUMO-mediated fusion expression of ABP-dHC-cecropin A from multiple joined genes in Escherichia coli. AB - The antimicrobial peptide ABP-dHC-cecropin A is a small cationic peptide with potent activity against a wide range of bacterial species. Evidence of antifungal activity has also been suggested; however, evaluation of this peptide has been limited due to the low expression of cecropin proteins in Escherichia coli. To improve the expression level of ABP-dHC-cecropin A in E. coli, tandem repeats of the ABP-dHC-cecropin A gene were constructed and expressed as fusion proteins (SUMO-nABP-dHC-cecropin, n = 1, 2, 3, 4) via pSUMO-nABP-dHC-cecropin A vectors (n = 1, 2, 3, 4). Comparison of the expression levels of soluble SUMO-nABP-dHC cecropin A fusion proteins (n = 1, 2, 3, 4) suggested that BL21 (DE3)/pSUMO-3ABP dHC-cecropin A is an ideal recombinant strain for ABP-dHC-cecropin A production. Under the selected conditions of cultivation and isopropylthiogalactoside (IPTG) induction, the expression level of ABP-dHC-cecropin A was as high as 65 mg/L, with ~21.3% of the fusion protein in soluble form. By large-scale fermentation, protein production reached nearly 300 mg/L, which is the highest yield of ABP-dHC cecropin A reported to date. In antibacterial experiments, the efficacy was approximately the same as that of synthetic ABP-dHC-cecropin A. This method provides a novel and effective means of producing large amounts of ABP-dHC cecropin A. PMID- 27377969 TI - Rapid quantitation of monoclonal antibody N-glyco-occupancy and afucosylation using mass spectrometry. AB - N-glyco-occupancy and afucoslyation level are two important quality attributes associated with N-glycosylation of therapeutic monoclonal antibodies (mAbs). We report here a fast mass spectrometry-based workflow for quantification of N glycan site-occupancy and afucoslyation level of mAbs with improved throughput, precision, sensitivity and robustness. This method uses the deglycosylation after the first GlcNAc and inter-chain reduction of the mAbs, followed by liquid chromatography/mass spectrometry (LC-MS) analysis. The entire process can be completed within one hour, which provides a rapid quantitation of N-glyco occupancy and afucosylation to support high-throughput cell line selection and process development for mAb biopharmaceuticals. PMID- 27377970 TI - A phase I dose-ranging study of bendamustine and rituximab in chronic lymphocytic leukemia patients with comorbidities. PMID- 27377971 TI - Lysobacter humi sp. nov., a bacterium isolated from rice field. AB - A novel bacterial strain THG-PC4T was isolated from soil sample of rice field and was characterized by using a polyphasic approach. Cells were Gram-negative, bright yellow colored, nonmotile and rod shaped. The strain was aerobic and catalase positive, optimum growth temperature, and pH were 28 degrees C and 7, respectively. On the basis of 16S rRNA gene sequence analysis, strain THG-PC4T belongs to the genus Lysobacter and is most closely related to Lysobacter fragariae KCTC 42236T, followed by Lysobacter oryzae KCTC 22249T, Lysobacter tyrosinelyticus KCTC 42235T, Lysobacter terrae KACC 17646T, Lysobacter yangpyeongensis KACC 11407T, Lysobacter rhizosphaerae KCTC 42237T and Lysobacter niabensis KACC 11587T. In DNA-DNA hybridization tests, the DNA relatedness between strain THG-PC4T and its closest phylogenetic neighbors was below 45 %. The DNA G + C content was 66.6 mol %, and the predominant respiratory quinone was ubiquinone-8. Flexirubin-type pigments were found to be present. The major cellular fatty acids were iso-C16:0, iso-C17:1 omega9c, iso-C17:0 and iso-C11:0 3OH. The predominant polar lipids were phosphatidylethanolamine and phosphatidylglycerol. The DNA-DNA hybridization, genotypic, chemotaxonomic and physiological data demonstrated that strain THG-PC4T represented a novel species within the genus Lysobacter, for which the name Lysobcater humi is proposed. The type strain is THG-PC4T (=KACC 18284T = CCTCC AB 2015292T). PMID- 27377972 TI - Transparent reporting for reproducible science. PMID- 27377973 TI - Sulforaphene inhibits triple negative breast cancer through activating tumor suppressor Egr1. AB - Sulforaphene (SFE, 4-methylsufinyl-3-butenyl isothiocyanate) is a member of isothiocyanates, which is derived from radish seeds. It has shown that multiple isothiocyanates, such as sulforaphane, can effectively inhibit cancer cell proliferation in vitro and in vivo. However, it is still largely unknown if SFE could impact breast cancer. In this study, we investigated the anticancer effects of SFE on triple negative breast cancer (TNBC) via a series of in vitro and in vivo assays. We found that SFE can significantly inhibit cell proliferation in multiple TNBC cell lines through inducing G2/M phase arrest as well as cell apoptosis. Nude mice xenograft assays support the anti-TNBC role of SFE in vivo. Interestingly, SFE can repress expression of cyclinB1, Cdc2, and phosphorylated Cdc2, and, then, induced G2/M phase arrest of TNBC cells. To identify SFE target genes, we detected genome-wide gene expression changes through gene expression profiling and observed 27 upregulated and 18 downregulated genes in MDA-MB-453 cells treated with SFE. Among these genes, Egr1 was successfully validated as a consistently activated gene after SFE treatment in TNBC MDA-MB-453 and MDA-MB-436 cells. Egr1 overexpression inhibited proliferation of TNBC cells. However, Egr1 knockdown using siRNAs significantly promoted TNBC cell growth, indicating the tumor suppressor nature of Egr1. In sum, we for the first time found that SFE might be a potential anti-TNBC natural compound and its antiproliferation effects might be mediated by tumor suppressor Egr1. PMID- 27377975 TI - A high-value cost conscious approach to minimize heparin induced thrombocytopenia antibody (HITAb) testing using the 4T score. AB - Heparin Induced Thrombocytopenia (HIT) is a serious complication from administration of heparin products. The 4T score is a validated pre-test probability tool to screen for HIT in hospitalized patients. As the negative predictive value (NPV) is very high further testing for HIT in patients with a low score can be avoided. Our objective was to determine trends at our hospital with respect to utilization of HIT antibody (HITAb) testing and evaluate economic burden from unnecessary HIT testing. A retrospective cohort review was performed on patients age 18 and above admitted to a tertiary care center from February 2013 to December 2014 who underwent HITAb testing. Surgical ICU patients were excluded. Patients were stratified into low, intermediate, and high risk for HIT based on the 4T model. Statistical analysis was performed using Chi square and regression models. Of 150 patients that underwent HITAb testing, 134 met inclusion criteria. 73 were male (54.47 %) and mean age was 55.50 +/- 17.27 years. 81 patients had a low 4T score 0-3. Analysis of testing trends showed 60.44 % of patients were tested for HITAb despite being low risk using the 4T model. Only three patients with low 4T score were positive on confirmatory SRA testing (NPV 96.29 % CI 95 = 89.56-99.23 %). Expenditure due to inappropriate testing and treatment was estimated at $103,348.13. The majority of HITAb testing was found unnecessary based on the investigator calculated 4T score. We propose implementation of an electronic medical record (EMR) based calculator in order to reduce unneeded tests and reduce use of costlier alternative anticoagulants. PMID- 27377974 TI - The genetic history of Cochin Jews from India. AB - Cochin Jews form a small and unique community on the Malabar coast in southwest India. While the arrival time of any putative Jewish ancestors of the community has been speculated to have taken place as far back as biblical times (King Solomon's era), a Jewish community in the Malabar coast has been documented only since the 9th century CE. Here, we explore the genetic history of Cochin Jews by collecting and genotyping 21 community members and combining the data with that of 707 individuals from 72 other Indian, Jewish, and Pakistani populations, together with additional individuals from worldwide populations. We applied comprehensive genome-wide analyses based on principal component analysis, F ST, ADMIXTURE, identity-by-descent sharing, admixture linkage disequilibrium decay, haplotype sharing, allele sharing autocorrelation decay and contrasting the X chromosome with the autosomes. We find that, as reported by several previous studies, the genetics of Cochin Jews resembles that of local Indian populations. However, we also identify considerable Jewish genetic ancestry that is not present in any other Indian or Pakistani populations (with the exception of the Jewish Bene Israel, which we characterized previously). Combined, Cochin Jews have both Jewish and Indian ancestry. Specifically, we detect a significant recent Jewish gene flow into this community 13-22 generations (~470-730 years) ago, with contributions from Yemenite, Sephardi, and Middle-Eastern Jews, in accordance with historical records. Genetic analyses also point to high endogamy and a recent population bottleneck in this population, which might explain the increased prevalence of some recessive diseases in Cochin Jews. PMID- 27377976 TI - Enzymatic Biofuel Cells on Porous Nanostructures. AB - Biofuel cells (BFCs) that utilize enzymes as catalysts represent a new sustainable and renewable energy technology. Numerous efforts have been directed to improve the performance of the enzymatic BFCs (EBFCs) with respect to power output and operational stability for further applications in portable power sources, self-powered electrochemical sensing, implantable medical devices, etc. The latest advances in EBFCs based on porous nanoarchitectures over the past 5 years are detailed here. Porous matrices from carbon, noble metals, and polymers promote the development of EBFCs through the electron transfer and mass transport benefits. Some key issues regarding how these nanostructured porous media improve the performance of EBFCs are also discussed. PMID- 27377977 TI - Relationship between long-term use of a typical antipsychotic medication by Chinese schizophrenia patients and the bone turnover markers serum osteocalcin and beta-CrossLaps. AB - BACKGROUND: Increasing evidence shows that schizophrenia patients with long-term exposure to antipsychotic medications have decreased bone mass, which suggests that they are at a high risk of osteoporosis. However, the mechanism underlying this remains unclear. In this study, we selected two bone turnover markers to explore whether atypical antipsychotics can affect bone metabolism and identified possible influencing factors. METHODS: A total of 116 schizophrenia patients (18 40years old) participated in the study. The subjects included 31 drug-naive first episode patients and 85 patients who had undergone atypical antipsychotic monotherapy for at least 6months. A total of 71 subjects were assigned as normal controls. Demographic and physical examination data were analyzed for all subjects. The positive and negative syndrome scale (PANSS) was used to assess psychopathology in schizophrenia patients. Levels of the bone turnover markers osteocalcin and beta-CrossLaps were measured. Serum prolactin (PRL), lipid, sex hormone, glucose, insulin, and parathyroid hormone levels were also measured. RESULTS: The serum beta-CrossLaps levels of patients who had been treated with atypical antipsychotics were higher compared with those of drug-naive first episode patients and normal subjects. Atypical antipsychotics, schizophrenia, age, gender, and body mass index, as well as serum levels of PRL, triglyceride, high-density lipoprotein cholesterol, glucose, and testosterone, were significantly associated with serum osteocalcin and beta-CrossLaps levels. Serum insulin was only positively associated with serum osteocalcin, whereas estradiol was only negatively associated with serum beta-CrossLaps. CONCLUSION: Patients who had been treated with atypical antipsychotics had accelerated bone resorption. Our findings uncover a link between atypical antipsychotics and bone metabolism, possibly through abnormalities in glucose and lipid metabolism and insulin resistance. PMID- 27377978 TI - Validation of the Pediatric Catatonia Rating Scale (PCRS). AB - INTRODUCTION: Despite the increased recognition of catatonia in children and adolescents, no specific assessment instrument has been validated in this population. METHOD: Within the context of a prospective study on catatonia, we developed the Pediatric Catatonia Rating Scale (PCRS, maximum score=60), adapted from the Bush and Francis Catatonia Rating Scale for its use in child and adolescent inpatients. We assessed the psychometric properties of the PCRS by measuring its internal consistency, construct validity, and factor structure. Bivariate analyses were performed to compare the different diagnostic patient groups across the extracted factors. RESULTS: Internal consistency was moderate (Cronbach's alpha for total score=0.67) suggesting multidimensionality. Multiple factors underlie the PCRS items, as revealed by factor analysis. Four distinct dimensions of catatonic symptoms were identified and accounted for 44% of total variance: a "negative withdrawal" factor (with mutism, negativism, and social withdrawal), a "catalepsy" factor (with posturing and waxy flexibility), an "abnormal movements" factor (with mannerisms and stereotypes) and an "echo phenomenon" factor (with echolalia and echopraxia). Receiver operating characteristic (ROC) analysis showed that the PCRS performance in discriminating individuals with catatonia vs. those without catatonia was excellent for a threshold>=9 (Area Under the Curve=0.983) in this sample. DISCUSSION: These results support the validity of the PCRS among children and adolescent inpatients. With regard to such analyses, the internal structure of catatonic syndrome in children and adolescents is roughly comparable with the adult form, except the lack of a "hyperactive/excitement" dimension. PMID- 27377979 TI - Phase Transfer of Palladized Nanoscale Zerovalent Iron for Environmental Remediation of Trichloroethene. AB - Palladium-doped nanoscale zerovalent iron (Pd-NZVI) has been shown to degrade environmental contaminants such as trichloroethene (TCE) to benign end-products through aqueous phase reactions. In this study we show that rhamnolipid (biosurfactant)-coated Pd-NZVI (RL-Pd-NZVI) when reacted with TCE in a 1-butanol organic phase with limited amounts of water results in 50% more TCE mass degradation per unit mass of Pd-NZVI, with a 4-fold faster degradation rate (kobs of 0.413 day(-1) in butanol organic phase versus 0.099 day(-1) in aqueous phase). RL-Pd-NZVI is preferentially suspended in water in biphasic organic liquid-water systems because of its hydrophilic nature. We demonstrate herein for the first time that their rapid phase transfer to a butanol/TCE organic phase can be achieved by adding NaCl and creating water-in-oil emulsions in the organic phase. The significant enhancement in reactivity is caused by a higher electron release (3e(-) per mole of Fe(0)) from Pd-NZVI in the butanol organic phase compared to the same reaction with TCE in the aqueous phase (2e(-) per mole of Fe(0)). XPS characterization studies of Pd-NZVI show Fe(0) oxidation to Fe(III) oxides for Pd NZVI reacted with TCE in the butanol organic phase compared to Fe(II) oxides in the aqueous phase, which accounted for differences in the TCE reactivity extents and rates observed in the two phases. PMID- 27377980 TI - [Auditing as a tool for ongoing improvement in the Stroke Care Plan of the Region of Aragon]. AB - INTRODUCTION: The Aragon Stroke Care Plan (PAIA) was created in 2008 within the framework of the Spanish National Health System. Monitoring hospital care of strokes by means of periodic audits was defined as one of its lines of work. AIM: To determine the quality of the hospital care process for stroke patients in Aragon by using quality indicators. MATERIALS AND METHODS: Three audits were carried out (in the years 2008, 2010 and 2012) following the same methodology, based on the retrospective review of a representative sample of admissions due to stroke in each of the general hospitals belonging to the Aragonese Health Service. Information was collected on 48 indicators selected according to their scientific evidence or clinical relevance. RESULTS: Altogether 1011 cases were studied (331 in the first audit, and 340 in the second and the third). Thirty-one indicators showed a significant improvement (some of the most notable being the indicators of quality of the medical record, neurological assessment, initial preventive measures and, especially relevant, performing the swallowing test), two underwent a decline in their condition (related with rehabilitation treatment) and 15 did not register any significant variation. CONCLUSIONS: The implementation of the PAIA has given rise to a notable improvement in most of the quality indicators evaluated, which reflects an ongoing improvement in hospital stroke care. The progressive generalisation of specialised care and the creation of stroke units are some of the determining factors. PMID- 27377981 TI - [Characteristics of patients with refractory epilepsy attended in a tertiary referral center in Costa Rica]. AB - INTRODUCTION: Thirty percent of patients with epilepsy have recurrent seizures, representing fifteen million people in the world. This population has been scarcely described. AIM: To characterize sociodemographic and clinically the patients diagnosed with refractory epilepsy in a tertiary referral hospital of the Costa Rican social security. PATIENTS AND METHODS: This study presents an analysis of all cases of refractory epilepsy evaluated at the epilepsy unit of San Juan de Dios Hospital from August, 2012 to October, 2014. RESULTS: Clinical records of 91 patients were studied; patients with psychogenic seizures were analyzed separately. The mean age of onset was 13.1 +/- 11.1 years, secondary generalized seizures were the predominant type (81.3%), the most frequent etiology was mesial temporal sclerosis (48.3%) and the majority had normal neurological exams and normal or low neuropsychological assessments. Around half (48.8%) of the patients had been medicated with a range of 4-6 antiepileptic drugs, being lamotrigine, carbamazepine, valproic acid and phenytoin the most prescribed. Treatment optimization, neurosurgery, and further analysis were standard recommendations. Sociodemographic characteristics, patient management, and antiepileptic drugs used are similar to the described in other latitudes. Differences between the age of onset and gender; seizure frequency and gender; age of onset and failed treatments and time of evolution of the disease and employment were observed. The percentage and characteristics of recurrent seizures of psychogenic nature found are comparable to other refractory epilepsy studies. CONCLUSION: Sociodemographic characteristics, management of patients, antiepileptic drugs used and the differences observed are similar to those previously described. PMID- 27377982 TI - [Cluster headache in pediatric population: four case reports and review of the literature]. AB - INTRODUCTION: Cluster headache is a rare cause of primary headache in children. We report four cases with a mean age of onset of 8.6, ranged from 2 to 13 years. CASE REPORTS: Three males and one female with onset at 2, 7, 13, and 12 years old, respectively, were included. The symptoms of all patients fulfill the criteria for the diagnosis of cluster headache according to the International Society of Headache. CONCLUSIONS: Despite being rare during childhood, cluster headache should be part of the differential diagnosis of headache in childhood. This report highlights the variable features of this disorder in children, often misdiagnosed. It can be useful in making a quick diagnosis and starting the appropriate treatment early. Verapamil was more effective than flunarizine in terminating the headache in our patients. Oxygen treatment and triptans resulted the treatments with the best response in acute cluster headache. PMID- 27377983 TI - [The neuroanatomy of attention deficit hyperactivity disorder: neuropsychological and clinical correlates]. AB - INTRODUCTION: The development of structural magnetic resonance scanning and new methods of analysis has made it possible to explore, in a hitherto unknown way, the neuroanatomical bases of attention deficit hyperactivity disorder (ADHD). Yet, little is known about the relation between the clinical symptoms and the neuropsychological dysfunctions characterising ADHD and the neuroanatomical alterations that are observed. AIM: To explore the relation between neuroanatomy, clinical features and neuropsychology in ADHD. DEVELOPMENT: At group level, there are a number of marked differences between the brain of children, adolescents and adults with ADHD and the brain of subjects with a typical development. These differences are observed cross-sectionally and longitudinally in all the measurements, both in the grey matter and in the white matter. Although still scarce, there is an increasing body of evidence showing that these differences are related with the core symptoms of the disorder and with the degree of clinical dysfunction. They also appear to be associated with cognitive functioning (mainly attention and inhibitory control). CONCLUSIONS: The relation among the different levels of analysis in the study of ADHD bring research closer to the clinical features and allows a better understanding and management of the disorder. Although progress is undoubtedly being made in this field, there are still many questions that need exploring in greater depth. There is a need for a better understanding of the association between the neuroanatomical measurements and each dimension of the symptoms, and their relationship with other neuropsychological processes that are also involved in the disorder. PMID- 27377985 TI - [XXXIII Reunion de la Sociedad Valenciana de Neurologia. Communications]. PMID- 27377984 TI - [Frenkel: one of the forerunners of neurorehabilitation?]. AB - Neurorehabilitation is understood as the process intended to reduce the deficiency, limitation of activity and restriction of participation experienced by people as a result of a neurological diseases, and where the professionals involved in this field will aim to reduce the functional involvement degree of the patient. Due to the ignorance existed about the plastic capacity in the nervous system in humans, the scientific origins of neurological rehabilitation is relatively recent, which are located around the Second World War. However, there are signs that the neurologist Heinrich Sebastian Frenkel (1860-1931) was able to establish the basis of neurorehabilitation before that time. There are historical concerning regarding the work conducted and published by Frenkel that would support the hypothesis, based on the characteristics of their treatment employed and documented methodologies, that what he called 'Ubungstherapie' (neurological gymnastic), it could be considered as the basis of what we consider today as modern neurorehabilitation. This knowledge could have been used by many authors who introduced those experiences and lessons learned to the multiple therapeutic methods that emerged after, even the most innovative and technological, while the roots of neurorehabilitation could be found at the end of the 19th century. PMID- 27377986 TI - [Parkinson's disease associated to mutation of the LRRK2 gene, mimicking multisystemic atrophy due to the combination of parkinsonism, early-onset dysautonomia and normal cardiac scintigraphy]. PMID- 27377987 TI - Comparing sensibility for touch, cold, and warmth in different skin areas. AB - The primary objective of this pilot study was to assess if the magnitude estimation of suprathreshold brushing, warmth (40 degrees C), and cold (25 degrees C) stimuli of the skin over the dorsum of the hand and the dorsum of the foot are comparable to the perceived intensity for the same stimuli applied to the skin over any of the following areas: forehead, m. trapezius, m. deltoideus, thoracic back, and lumbar back, respectively. Thirty-two subjects aged 18-64 years were included. Participants were examined by two physicians on two different occasions, 1-58 days apart. Participants rated the magnitude of the perceived sensation of each stimulus on an 11-point numerical rating scale (NRS) 0-10, where 0 was anchored to "no sensation at all for touch/cold/warmth" and 10 anchored to "the most intense imaginable non-painful sensation of touch/cold/warmth". The criterion for sensory equivalence for one modality was arbitrarily considered satisfactory if two regions had the same numerical rating +/-1 point in at least 85% of the individuals. Based on the pre-study criteria for sensory equivalence applied in this study only one area was found to be equivalent to the foot skin for the percept of brushing, that is, the skin over the deltoid muscle and one area for the hand, that is, the skin over the forehead. We failed to find any area with equivalent sensitivity to the hand or the foot for the cold or warm stimuli. PMID- 27377988 TI - The structure of liquid water beyond the first hydration shell. AB - To date there is a general consensus on the structure of the first coordination shells of liquid water, namely tetrahedral short range order of molecules. In contrast, little is known about the structure at longer distances and the influence of the tetrahedral molecular arrangement of the first shells on the order at these length scales. An expansion of the distance dependent excess entropy is used in this contribution to find out which molecular arrangements are important at each distance range. This was done by splitting the excess entropy into two parts: one connected to the relative position of two molecules and the other one related to their relative orientation. A transition between two previously unknown regimes in liquid water is identified at a distance of about ~6 A: from a predominantly orientational order at shorter distances to a regime at larger distances of up to ~9 A where the order is predominantly positional and molecules are distributed with the same tetrahedral symmetry as the very first molecules. PMID- 27377989 TI - Characterization of photosynthetic gas exchange in leaves under simulated adaxial and abaxial surfaces alternant irradiation. AB - Previous investigations on photosynthesis have been performed on leaves irradiated from the adaxial surface. However, leaves usually sway because of wind. This action results in the alternating exposure of both the adaxial and abaxial surfaces to bright sunlight. To simulate adaxial and abaxial surfaces alternant irradiation (ad-ab-alt irradiation), the adaxial or abaxial surface of leaves were exposed to light regimes that fluctuated between 100 and 1,000 MUmol m(-2) s(-1). Compared with constant adaxial irradiation, simulated ad-ab-alt irradiation suppressed net photosynthetic rate (Pn) and transpiration (E) but not water use efficiency. These suppressions were aggravated by an increase in alternant frequency of the light intensity. When leaves were transferred from constant light to simulated ad-ab-alt irradiation, the maximum Pn and E during the high light period decreased, but the rate of photosynthetic induction during this period remained constant. The sensitivity of photosynthetic gas exchange to simulated ad-ab-alt irradiation was lower on abaxial surface than adaxial surface. Under simulated ad-ab-alt irradiation, higher Pn and E were measured on abaxial surface compared with adaxial surface. Therefore, bifacial leaves can fix more carbon than leaves with two "sun-leaf-like" surfaces under ad-ab-alt irradiation. Photosynthetic research should be conducted under dynamic conditions that better mimic nature. PMID- 27377990 TI - MR lymphangiography in the treatment of lymphedema. AB - Lymphedema is a common condition frequently seen in cancer patients who have had lymph node dissection +/- radiation treatment. Traditional management is mainly non-surgical and unsatisfactory. Surgical treatment has relied on excisional techniques in the past. Physiologic operations have more recently been devised to help improve this condition. Assessing patients and deciding which of the available operations to offer them can be challenging. MRI is an extremely useful tool in patient assessment and treatment planning. J. Surg. Oncol. 2017;115:18 22. (c) 2016 Wiley Periodicals, Inc. PMID- 27377991 TI - Ultrasound-Induced Organogel Formation Followed by Thin Film Fabrication via Simple Doctor Blading Technique for Field-Effect Transistor Applications. AB - We demonstrate doctor blading technique to fabricate high performance transistors made up of printed small molecular materials. In this regard, we synthesize a new soluble phthalocyanine, tetra-n-butyl peripheral substituted copper(II) phthalocaynine (CuBuPc), that can easily undergo gel formation upon ultrasonic irradiation, leading to the formation of three-dimensional (3D) network composed of one-dimensional (1D) nanofibers structure. Finally, taking the advantage of thixotropic nature of the CuBuPc organogel, we use the doctor blade processing technique that limits the material wastage for the fabrication of transistor devices. Due to the ultrasound induced stronger pi-pi interaction, the transistor fabricated by doctor blading based on CuBuPc organogel exhibits significant increase in charge carrier mobility in comparison with other solution process techniques, thus paving a way for a simple and economically viable preparation of electronic circuits. PMID- 27377992 TI - Cost-Effectiveness Analysis of the Use of Probiotics for the Prevention of Clostridium difficile-Associated Diarrhea in a Provincial Healthcare System. AB - OBJECTIVE To conduct a full economic evaluation assessing the costs and consequences related to probiotic use for the primary prevention of Clostridium difficile-associated diarrhea (CDAD). DESIGN Cost-effectiveness analysis using decision analytic modeling. METHODS A cost-effectiveness analysis was used to evaluate the risk of CDAD and the costs of receiving oral probiotics versus not over a time horizon of 30 days. The target population modeled was all adult inpatients receiving any therapeutic course of antibiotics from a publicly funded healthcare system perspective. Effectiveness estimates were based on a recent systematic review of probiotics for the primary prevention of CDAD. Additional estimates came from local data and the literature. Sensitivity analyses were conducted to assess how plausible changes in variables impacted the results. RESULTS Treatment with oral probiotics led to direct costs of CDN $24 per course of treatment per patient. On average, patients treated with oral probiotics had a lower overall cost compared with usual care (CDN $327 vs $845). The risk of CDAD was reduced from 5.5% in those not receiving oral probiotics to 2% in those receiving oral probiotics. These results were robust to plausible variation in all estimates. CONCLUSIONS Oral probiotics as a preventive strategy for CDAD resulted in a lower risk of CDAD as well as cost-savings. The cost-savings may be greater in other healthcare systems that experience a higher incidence and cost associated with CDAD. Infect Control Hosp Epidemiol 2016;37:1079-1086. PMID- 27377993 TI - Nurse Faculty Beliefs and Teaching Practices for the Care of the Cancer Survivor in Undergraduate Nursing Curricula. AB - As the number of individuals surviving cancer continues to rise, short- and long term effects of cancer and its treatment that result in physical, psychosocial, and spiritual needs unique to the care of the cancer survivor has not been addressed in nursing curricula. The Institute of Medicine (IOM, 2005) recommends that all health care providers are educated on the care of cancer survivors. This descriptive qualitative study explored faculty beliefs and practices regarding the inclusion of caring for the cancer survivor in undergraduate nursing curricula. Faculty knowledge of the term "cancer survivor" and their beliefs and practices regarding the placement of theory and clinical experiences on cancer survivorship were explored through face-to-face semi-structured interviews. Qualitative content analysis revealed themes and patterns related to the barriers and facilitators for disseminating information on the gap in content on care of the cancer survivor. Seven themes emerged from the content analysis of the interviews. These were as follows: (1) descriptions of cancer survivorship; (2) beliefs on inclusion of cancer survivorship care within undergraduate nursing curriculum; (3) established content on cancer survivorship care: teaching practices; (4) gaps in content on cancer survivorship care; (5) lack of supportive literature on cancer survivorship care; (6) clinical sites providing opportunities for cancer survivorship care: planned versus unplanned; and (7) barriers and facilitators to the inclusion of cancer survivorship in undergraduate nursing curricula. This study reveals the need for faculty education on the care of cancer survivors and a revision of undergraduate curriculum content. PMID- 27377994 TI - Commentary: Enhanced Monitoring of the Preterm Infant during Stabilization in the Delivery Room. PMID- 27377995 TI - Radical Beckmann Rearrangement and Its Application in the Formal Total Synthesis of Antimalarial Natural Product Isocryptolepine via C-H Activation. AB - The Beckmann rearrangement of ketoximes, mediated by ammonium persulfate-dimethyl sulfoxide as a reagent, has been achieved under neutral conditions. Based on the radical trapping and (18)O-labeling experiments, the transformation follows a mechanism involving a radical pathway. The scope and generality of the developed protocol has been demonstrated by 19 examples. The developed protocol and Pd catalyzed intramolecular double C-H activation were used as key steps in the formal total synthesis of antimalarial natural product isocryptolepine. PMID- 27377997 TI - A practical approach to ichthyoses with systemic manifestations. AB - Inherited ichthyoses are rare disorders in terms of patient numbers, but abundant in terms of clinical-genetic subtypes. These disorders are often associated with severe systemic manifestations, in addition to significant medical, cosmetic and social problems. There are 17 subtypes of syndromic ichthyosis identified so far and most patients with these syndromes are living in countries with high consanguinity rates. Frequently, clinicians cannot make a definitive diagnosis and patients are not managed properly owing to the rarity and complexity of these disorders. These difficulties make this group of ichthyosis and the patients living with them 'orphan'. After skin and skin appendages, nervous system is the most frequently involved system in ichthyosis syndromes. Thus, association of ichthyosis with neurological symptoms provides an important clue for diagnosis. In this article, we aim to increase clinicians' comprehension of ichthyosis syndromes by providing a symptomatology-based approach based on this observation. Additionally, we provide a review of ichthyosis syndromes, with special emphasis on neurological symptoms, hoping to attract interest to this complicated field. PMID- 27377998 TI - Supramolecular guest relay using host-protein nanocavities: an application of host-induced guest protonation. AB - Small drug molecules and other important metabolites are delivered via a suitable carrier protein-mediated transport through a specific receptor. The process is highly coordinated and associated with complexation induced properties of deliverable molecules. To get a molecular insight, in this report, we tried to mimic the delivery process to know how the carrier protein relocates the drug molecule from the macrocyclic host cavity to its binding pocket and how the electronic and the chemical properties of the guest get altered. Bovine and human serum albumin (BSA and HSA) were used as the model carrier proteins which can snatch out 6-propanoyl-2-(N,N-dimethylamino)naphthalene (PRO), dye used as a drug model (known to bind at the drug-binding pocket of the carrier protein), from the cucurbit[7]uril (CB7) cavity, a potential drug delivery carrier. Prior to performing the fluorescence-based bio-supramolecular relocation assay using BSA and HSA, CB7 and PRO, we have investigated the effect of CB7 encapsulation and protonation on the fluorescence properties of PRO. A significant shift in the pKa value from 3.4 to 6.6 (ca. 3.2 logarithmic units) of PRO was observed upon encapsulation with CB7, which causes a huge fluorescence quenching even at neutral pH. The binding affinity of protonated and neutral PRO for CB7 also confirms a 3.2 unit shift in the acid-dissociation constant. A displacement assay using a strong CB7 binder, viz., 1,6-diaminohexane, confirms encapsulation of PRO in the CB7 cavity. Encapsulation of neutral PRO by CB7 shows a significant fluorescence enhancement accompanied by a ~35 nm blue shift in the emission maxima. PMID- 27377996 TI - Transnasal delivery of human A-beta peptides elicits impaired learning and memory performance in wild type mice. AB - BACKGROUND: Murine models of Alzheimer's disease (AD) are mainly based on overexpression of pathologic amyloid precursor protein and/or presenilins. Those genes resemble underlying cause of early onset type of AD while about 99 % of all human cases are to be characterized as sporadic, late onset. Appropriate animal models for this type of AD are still missing. We here investigated, if transnasal delivery of A-beta 42 peptides might serve to mimic pathological effects in mice. RESULTS: A-beta 42 peptides, used for the behavioral study, showed the expected dose-dependent toxicity in neur oblastoma cell line SH-SY5Y and were able to form higher molecular weight species in vitro. Upon delivery into nostrils of wild type mice, protein bands that might represent aggregation products of the exogenously applied human A-beta 42 were only observed in total brain homogenates from mice pre-treated with mannitol. By using TAMRA-labeled A-beta 42 peptides we demonstrated, that transport throughout the brain was achieved already 1 h after administration. FVB/N mice treated with A-beta 42 for 3 days were significantly impaired in the cue-retention condition of the fear conditioning task as compared to controls whereas A-beta-treated C57B6/J mice were impaired in the context condition. In the Morris water maze test, these mice also displayed a delayed learning performance, indicated by significantly longer time to find the platform. Those deficits were also seen for memory performance in the probe trial as measured by number of crossings of the former platform position and time spent in the goal quadrant. CONCLUSIONS: Existing AD mouse models are of genetic origin and need prolonged housing time before onset of pathology. Our short-term treatment induced learning and memory deficits via exogenous application of A beta peptides comparable to those observed for the transgenic animals. With the transnasal A-beta 42 treatment we present an approach to investigate purely A beta related changes suitable as a model for symptoms of Alzheimer's dementia (AD). Resulting behavioral deficits were indicative for familial type of Alzheimer's disease as well as for the late onset variant. PMID- 27377999 TI - Objective assessment of trismus in oral and oropharyngeal cancer patients treated with intensity-modulated radiation therapy (IMRT). AB - PURPOSE: The aim of this study was to estimate the prevalence of trismus in oral and oropharyngeal cancer patients (OOPC) treated with intensity-modulated radiation therapy (IMRT) and to identify the role of risk factors in patients who developed trismus. MATERIALS AND METHODS: A retrospective cohort study of OOPC treated with IMRT in our institution from 2009 to 2014 was performed. Patients eligible for this study had pre-RT and post-RT maximal inter-incisal opening (MIO) measurements at 6-48 months post-RT, treated with high-dose radiation (>=60 Gy) and pre-RT MIO >=36 mm. A descriptive analysis to identify the incidence of trismus, with trismus stated as MIO <=35 mm at or after 6 months post-RT measurement was performed. The role of risk factors such as age, gender, tumor site, tumor size (T), tumor stage, pre-RT MIO measurements and radiation dose to the tumor were assessed using Fisher exact test and the radiation doses to the ipsilateral muscles of mastication in patients who developed trismus were assessed by matching with control (non-trismus) patients using Wilcoxon Signed Rank test. RESULTS: The study consisted of 54 patients with a median age of 55 years and 81% were males. The median follow-up time was 10 months. The prevalence of trismus was 14.8%. Patients with pre-RT MIO measurements <=40 mm were at risk of developing trismus (P < 0.001). In trismus patients, the average mean radiation dose to the masseter and medial pterygoid muscles was numerically higher but not significantly different (P = 0.08; P = 0.22, respectively) to matched control patients. Age, gender, radiation dose to the tumor, tumor site, size (T) and stage were also found to be not significant. CONCLUSION: Pre-RT MIO measurement was a significant risk factor for the development of trismus. However, this is a non-modifiable factor. Limiting radiation dose to the muscles of mastication could prevent this complication. PMID- 27378000 TI - Comparison of the analgesic efficacy of preoperative/postoperative oral dexketoprofen trometamol in third molar surgery: A randomized clinical trial. AB - The aim of this study was to compare the efficacy of preoperative and postoperative dexketoprofen trometamol for pain control after third molar surgery. Sixty subjects indicated for impacted mandibular third molar surgery were randomly assigned to two groups: preoperative (group 1, n = 30) and postoperative (group 2, n = 30) administration. Group 1 received 25 mg of dexketoprofen trometamol 30 min before surgery and 1 placebo capsule (same color and size with active drug) immediately after surgery. Group 2 received the placebo capsule 30 min before surgery and 25 mg of dexketoprofen trometamol immediately after surgery. Pain intensity was assessed using a numeric rating scale (NRS) during the first 8 h. The time of the need for a second dose of dexketoprofen trometamol, after the first administration, was recorded. The data were analyzed using mixed-model repeated-measures (MMRM), Wilcoxon rank-sum, and Kaplan-Meier analysis. After the 8 h period, no statistically significant difference was observed in the intensity of pain (MMRM, p = 0.41); and no significant difference in the time for a second dose (p = 0.956). In conclusion, preoperative administration of dexketoprofen trometamol is a reasonable clinical approach that is as effective as conventional postoperative pharmacological treatment, with the advantage of allowing early analgesia before pain develops. (ClinicalTrials.gov: NCT02380001). PMID- 27378001 TI - Apert syndrome: Surgical outcomes and perspectives. AB - PURPOSE: Apert syndrome is a rare congenital malformation with severe craniofacial anomalies. The aim of this study was to review the outcomes of craniofacial and neurosurgical interventions in Apert syndrome patients treated at a single institution. MATERIALS AND METHODS: A retrospective review of all patient records with a diagnosis of Apert syndrome assessed and managed in the Australian Craniofacial Unit (ACFU) from 1985 to 2013 was conducted. RESULTS: A total of 94 patients were identified, and 130 transcranial procedures were performed. Of the patients, 83 underwent a fronto-orbital advancement (FOA) as their primary procedure, and 18 patients also underwent a posterior vault procedure. Twenty patients underwent a fronto-facial monobloc advancement. Overall, 70% of patients underwent at least 2 transcranial procedures. Shunts were inserted in 2 patients preoperatively and in 5 patients postoperatively for cerebrospinal fluid (CSF) leaks or acute hydrocephalus. Re-do FOAs were performed in 8 patients. Patients who underwent an FOA at the age of more than 18 months had no recurrence of raised intracranial pressure (ICP). Of 18 patients who also underwent a posterior vault procedure, 1 patient had recurrence of raised ICP. Midfacial surgery was performed early if there was evidence of obstructive sleep apnoea (OSA), but delayed midfacial surgery was preferred. Complications were reported in 18% of procedures. The most common complications were CSF leaks and acute hydrocephalus. CONCLUSION: Shunting is rarely required in Apert syndrome patients, confirming a predominantly nonprogressive ventriculomegaly. FOA appears to be a more stable procedure when performed at an age of more than 18 months. Undergoing a posterior vault procedure may reduce the risk of recurrent raised ICP and lead to fewer transcranial procedures needed in childhood. Midfacial surgery should be delayed until adolescence where there is no evidence of OSA, psychological disturbance, or complications of exorbitism. Complications are rare when these patients are treated by an experienced craniofacial team. PMID- 27378002 TI - Factors related to doctors' choice of rural pathway in general practice specialty training. AB - OBJECTIVE: To investigate the factors eligible applicants consider in electing for a rural pathway into specialty training. DESIGN: Cohort study. SETTING: Australia. PARTICIPANTS: Applicants to the Australian General Practice Training program. MAIN OUTCOME MEASURES: Applicants' initial preference of either a general or rural pathway to undertake specialty training. RESULTS: Of the 2,221 applicants, 45% were Australian Medical Graduates (AMGs), 27% Foreign Graduates of Accredited Medical Schools (FGAMS) and 29% International Medical Graduates (IMGs). Through government regulation, two thirds (70%) were eligible to train on both general and rural pathways and a third (30%) were required to train rurally. For applicants eligible for general pathway (n = 1552), those with rural background [Odds Ratio (OR) = 3.7, 95% CI 2.7-5.2] and rural clinical school experience (OR = 2.0, 95% CI 1.5-2.8) were more likely to choose the rural pathway. In addition, FGAMS who were eligible for the general pathway were less likely to choose a rural pathway when compared with IMGs (OR = 0.33, 95%CI 0.1 = 0.7). In applicants who changed their training pathway from their initial to revised preference, lower Multiple-Mini-Interview (OR = 0.54, 95% CI 0.43-0.66) and Situational Judgement Test z-scores (OR = 0.68, 95% CI 0.56-0.83) were associated with a higher probability of changing from a general to rural pathway preference. CONCLUSION: For those eligible for a general or rural pathway, rural background and rural clinical school experience are associated with the decision to elect for rural training. Targeted support for international and foreign graduates of Australia/New Zealand schools may influence them to train rurally. PMID- 27378003 TI - Heart failure: health is priceless... but still expensive. PMID- 27378004 TI - A multiscale model of placental oxygen exchange: The effect of villous tree structure on exchange efficiency. AB - The placenta is critical to fetal health during pregnancy as it supplies oxygen and nutrients to maintain life. It has a complex structure, and alterations to this structure across spatial scales are associated with several pregnancy complications, including intrauterine growth restriction (IUGR). The relationship between placental structure and its efficiency as an oxygen exchanger is not well understood in normal or pathological pregnancies. Here we present a computational framework that predicts oxygen transport in the placenta which accounts for blood and oxygen transport in the space around a placental functional unit (the villous tree). The model includes the well-defined branching structure of the largest villous tree branches, as well as a smoothed representation of the small terminal villi that comprise the placenta's gas exchange interfaces. The model demonstrates that oxygen exchange is sensitive to villous tree geometry, including the villous branch length and volume, which are seen to change in IUGR. This is because, to be an efficient exchanger, the architecture of the villous tree must provide a balance between maximising the surface area available for exchange, and the opposing condition of allowing sufficient maternal blood flow to penetrate into the space surrounding the tree. The model also predicts an optimum oxygen exchange when the branch angle is 24 degrees , as villous branches and TBs are spread out sufficiently to channel maternal blood flow deep into the placental tissue for oxygen exchange without being shunted directly into the DVs. Without concurrent change in the branch length and angles, the model predicts that the number of branching generations has a small influence on oxygen exchange. The modelling framework is presented in 2D for simplicity but is extendible to 3D or to incorporate the high-resolution imaging data that is currently evolving to better quantify placental structure. PMID- 27378005 TI - gDNA-Prot: Predict DNA-binding proteins by employing support vector machine and a novel numerical characterization of protein sequence. AB - DNA-binding proteins are the functional proteins in cells, which play an important role in various essential biological activities. An effective and fast computational method gDNA-Prot is proposed to predict DNA-binding proteins in this paper, which is a DNA-binding predictor that combines the support vector machine classifier and a novel kind of feature called graphical representation. The DNA-binding protein sequence information was described with the 20 probabilities of amino acids and the 23 new numerical graphical representation features of a protein sequence, based on 23 physicochemical properties of 20 amino acids. The Principal Components Analysis (PCA) was employed as feature selection method for removing the irrelevant features and reducing redundant features. The Sigmod function and Min-max normalization methods for PCA were applied to accelerate the training speed and obtain higher accuracy. Experiments demonstrated that the Principal Components Analysis with Sigmod function generated the best performance. The gDNA-Prot method was also compared with the DNAbinder, iDNA-Prot and DNA-Prot. The results suggested that gDNA-Prot outperformed the DNAbinder and iDNA-Prot. Although the DNA-Prot outperformed gDNA Prot, gDNA-Prot was faster and convenient to predict the DNA-binding proteins. Additionally, the proposed gNDA-Prot method is available at http://sourceforge.net/projects/gdnaprot. PMID- 27378006 TI - Design principles for the analysis and construction of robustly homeostatic biological networks. AB - Homeostatic biological systems resist external disturbances, allowing cells and organisms to maintain a constant internal state despite perturbations from their surroundings. Many biological regulatory networks are known to act homeostatically, with examples including thermal adaptation, osmoregulation, and chemotaxis. Understanding the network topologies (sets of regulatory interactions) and biological parameter regimes that can yield homeostasis in a biological system is of interest both for the study of natural biological system, and in the context of designing new biological control schemes for use in synthetic biology. Here, we examine the mathematical properties of a function that maps a biological system's inputs to its outputs, we have formulated a novel criterion (the "cofactor condition") that compactly describes the conditions for homeostasis. We further analyze the problem of robust homeostasis, wherein the system is required to maintain homeostatic behavior when its parameter values are slightly altered. We use the cofactor condition to examine previously reported examples of robust homeostasis, showing that it is a useful way to unify a number of seemingly different analyses into a single framework. Based on the observation that all previous robustly homeostatic examples fall into one of three classes, we propose a "strong cofactor condition" and use it to provide an algorithm for designing new robustly homeostatic biological networks, giving both their topologies and constraints on their parameter values. Applying the design algorithm to a three-node biological network, we construct several robustly homeostatic genetic networks, uncovering network topologies not previously identified as candidates for exhibiting robust homeostasis. PMID- 27378008 TI - Bacterial bloodstream infections in pediatric allogeneic hematopoietic stem cell recipients before and after implementation of a central line-associated bloodstream infection protocol: A single-center experience. AB - INTRODUCTION: There are only few reports describing the influence of central line associated bloodstream infection (CLABSI) prevention strategies on the incidence of bacterial bloodstream infections (BBSIs). METHODS: We performed a retrospective cohort study among pediatric recipients of allogeneic hematopoietic stem cell transplantation (allo-HCT) to assess potential changes in BBSI rates during 3 time periods: pre-CLABSI prevention era (era 1, 2004-2005), CLABSI prevention implementation era (era 2, 2006-2009), and maintenance of CLABSI prevention era (era 3, 2010-2012). BBSI from day 0-365 following allo-HCT were studied. The comparison of person-years incidence rates among different periods was carried out by Poisson regression analysis. RESULTS: The mean age of patients was 10.0 years. During the study period, 126 (65%) of 190 patients had at least a single BBSI. From day 0-30, day 31-100, day 101-180, and day 181-365, 20%, 28%, 30%, and 17% of patients, respectively, experienced BBSIs. The rate of Staphylococcus epidermidis and gram-negative pathogens significantly declined from 3.16-0.93 and 6.32-2.21 per 100 person-months during era 1 and era 3, respectively (P = .001). CONCLUSIONS: Patients undergoing allo-HCT during era 3 were associated with decreased risk of BBSI (P = .012). Maintenance of CLABSI protocols by nursing staff and appropriate education of other care providers is essential to lower incidence of BBSI in this high-risk population, and further strategies to decrease infection burden should be studied. PMID- 27378009 TI - Chlorhexidine-silver sulfadiazine-impregnated venous catheters are efficient even at subclavian sites without tracheostomy. AB - BACKGROUND: Chlorhexidine-silver sulfadiazine (CHSS)-impregnated catheters have been found to decrease the risk of catheter-related bloodstream infection (CRBSI) and central venous catheter (CVC)-related costs. However, there are no published data about cost-effectiveness of the use of CHSS-impregnated catheters in subclavian venous access without the presence of tracheostomy (thus, with a very low risk of CRBSI). That was the objective of this study. METHODS: This was a retrospective study of patients admitted to a mixed intensive care unit who underwent placement of subclavian venous catheters without the presence of tracheostomy. RESULTS: Patients with standard catheters (n = 747) showed a higher CRBSI incidence density (0.95 vs 0/1,000 catheter-days; P = .02) and higher CVC related cost per day ($3.78 +/- $7.43 vs $3.31 +/- $2.72; P < .001) than patients with a CHSS-impregnated catheter (n = 879). Exact logistic regression analysis showed that catheter duration (P = .02) and the type of catheter used (P = .01) were associated with the risk of CRBSI. Kaplan-Meier method showed that CHSS impregnated catheters were associated with more prolonged CRBSI-free time than standard catheters (log-rank = 9.76; P = .002). Poisson regression analysis showed that CHSS-impregnated catheters were associated with a lower central venous catheter-related cost per day than standard catheters (odds ratio, 0.87; 95% confidence interval, 0.001-0.903; P < .001). CONCLUSIONS: The use of CHSS impregnated catheters is an effective and efficient measure for the prevention of CRBSI even at subclavian venous access sites without the presence of tracheostomy. PMID- 27378010 TI - Impact of a novel, resource appropriate resuscitation curriculum on Nicaraguan resident physician's management of cardiac arrest. AB - PURPOSE: Project Strengthening Emergency Medicine, Investing in Learners in Latin America (SEMILLA) created a novel, language and resource appropriate course for the resuscitation of cardiac arrest for Nicaraguan resident physicians. We hypothesized that participation in the Project SEMILLA resuscitation program would significantly improve the physician's management of simulated code scenarios. METHODS: Thirteen Nicaraguan resident physicians were evaluated while managing simulated cardiac arrest scenarios before, immediately, and at 6 months after participating in the Project SEMILLA resuscitation program. This project was completed in 2014 in Leon, Nicaragua. The Cardiac Arrest Simulation Test (CASTest), a validated scoring system, was used to evaluate performance on a standardized simulated cardiac arrest scenario. Mixed effect logistic regression models were constructed to assess outcomes. RESULTS: On the pre-course simulation exam, only 7.7% of subjects passed the test. Immediately post-course, the subjects achieved a 30.8% pass rate and at 6 months after the course, the pass rate was 46.2%. Compared with pre-test scores, the odds of passing the CASTest at 6 months after the course were 21.7 times higher (95% CI 4.2 to 112.8, P<0.001). Statistically significant improvement was also seen on the number of critical items completed (OR=3.75, 95% CI 2.71-5.19), total items completed (OR=4.55, 95% CI 3.4-6.11), and number of "excellent" scores on a Likert scale (OR=2.66, 95% CI 1.85-3.81). CONCLUSIONS: Nicaraguan resident physicians demonstrate improved ability to manage simulated cardiac arrest scenarios after participation in the Project SEMILLA resuscitation course and retain these skills. PMID- 27378011 TI - Effectiveness of pre-admission data and letters of recommendation to predict students who will need professional behavior intervention during clinical rotations in the United States. AB - The study aimed at finding the value of letters of recommendation in predicting professional behavior problems in the clinical portion of a Doctor of Physical Therapy program learning cohorts from 2009-2014 in the United States. De identified records of 137 Doctor of Physical Therapy graduates were examined by the descriptive statistics and comparison analysis. Thirty letters of recommendation were investigated based on grounded theory from 10 student applications with 5 randomly selected students of interest and 5 non-students of interest. Critical thinking, organizational skills, and judgement were statistically significant and quantitative differentiating characteristics. Qualitatively, significant characteristics of the student of interest included effective communication and cultural competency. Meanwhile, those of nonstudents of interest included conflicting personality descriptor, commitment to learning, balance, teamwork skills, potential future success, compatible learning skills, effective leadership skills, and emotional intelligence. Emerged significant characteristics did not consistently match common non-professional behavior issues encountered in clinic. Pre-admission data and letters of recommendation appear of limited value in predicting professional behavior performance in clinic. PMID- 27378012 TI - Congenital infundibulopelvic stenosis: Indications for intervention, surgical technique, and review of literature. AB - INTRODUCTION: Congenital infundibulopelvic stenosis (IFPS) is a rare renal dysmorphism marked by dilated calyces proximal to diminutive infundibulum and renal pelvises. The entity is theorized to exist on the spectrum of congenital obstructive renal diseases between ureteropelvic junction obstruction and multicystic dysplasia. OBJECTIVE: This case series sought to review and present the surgical management of three cases of IFPS with progressive renal insufficiency. MATERIALS AND METHODS: After Institute Review Board approval, we reviewed three cases of IFPS treated by a single surgeon over a 20-year period. All cases displayed evidence of progressive renal decline. The first case of a 16 year-old female had IFPS in a solitary kidney, with previous contralateral nephrectomy of a multicystic dysplastic kidney. The second case, a 17-year-old male, presented after blunt trauma to the ipsilateral flank. The third case of a 10-year-old female presented with microhematuria, mild azotemia and bilateral IFPS. RESULTS: Our current surgical management has evolved from renal sinus exposure and multiple infundibuloplasties in the first case to preoperative three dimensional mapping of the dilated calyceal system with intraoperative ultrasonography for selective calicocalicostomies draining to a lower pole ureterocalicostomy in the third case. Our first case, treated with multiple infundibuloplasties experienced slow renal decline into her 20s, and the later cases, treated with calicocalicostomies, have experienced stable to mild loss of renal function with ongoing nephrological follow-up. DISCUSSION: IFPS is a complex pediatric urology problem without a clear treatment algorithm. The goal of surgical intervention is to offer an opportunity to halt or reduce progressive renal insufficiency. Our current surgical approach utilizes preoperative three dimensional modeling via magnetic resonance urography to guide placement of multiple calicocalicostomies draining to a lower pole ureterocalicostomy. CONCLUSIONS: Not all cases of IFPS require surgical intervention. We have intervened in cases of IFPS with progressive hydronephrosis or worsening renal insufficiency with acceptable results. PMID- 27378013 TI - Cognitive Processing Therapy for Spanish-speaking Latinos: A Formative Study of a Model-Driven Cultural Adaptation of the Manual to Enhance Implementation in a Usual Care Setting. AB - OBJECTIVE: As part of a larger implementation trial for cognitive processing therapy (CPT) for posttraumatic stress disorder (PTSD) in a community health center, we used formative evaluation to assess relations between iterative cultural adaption (for Spanish-speaking clients) and implementation outcomes (appropriateness and acceptability) for CPT. METHOD: Qualitative data for the current study were gathered through multiple sources (providers: N = 6; clients: N = 22), including CPT therapy sessions, provider fieldnotes, weekly consultation team meetings, and researcher fieldnotes. Findings from conventional and directed content analysis of the data informed refinements to the CPT manual. RESULTS: Data-driven refinements included adaptations related to cultural context (i.e., language, regional variation in wording), urban context (e.g., crime/violence), and literacy level. Qualitative findings suggest improved appropriateness and acceptability of CPT for Spanish-speaking clients. CONCLUSION: Our study reinforces the need for dual application of cultural adaptation and implementation science to address the PTSD treatment needs of Spanish-speaking clients. PMID- 27378014 TI - Non-invasive measurement of cardiac output using AESCULON(r) mini after Fontan operation. AB - BACKGROUND: Electrical velocimetry correlates well with established methods of measuring cardiac output (CO) such as thermodilution and echocardiography. In this study, we compared the cardiac function of children with single right ventricle (SRV) and single left ventricle (SLV) on non-invasive postoperative measurement of hemodynamic parameters using AESCULON(r) mini. METHODS: Demographic, preoperative, and perioperative data were obtained from medical records. We retrospectively reviewed the AESCULON mini data of 21 patients with single ventricle who underwent Fontan operation. The patients were divided into two groups according to morphologic diagnosis: SRV (n = 9) and SLV (n = 12). The following hemodynamic parameters were analyzed: stroke volume (SV); CO; cardiac index (CI); stroke volume variation (SVV); and ventricular ejection time (VET). RESULTS: Hemodynamic parameters were as follows (SRV vs SLV): heart rate (HR), 140.5 beats/min versus 121 beats/min; SV, 14.5 mL vs 19.9 mL; CO, 2 L/min vs 2.3 L/min; CI, 4.3 L/min/m2 versus 4.4 L/min/m2 ; SVV, 15.5% versus 13.9%; and VET, 167.7 s versus 197.7 s. HR and VET were statistically different between the two groups. CONCLUSIONS: CI does not differ with laterality of the single ventricle. SRV VET, however, was significantly shorter than SLV VET in the acute postoperative period. Conversely, SRV HR was higher than SLV HR, which may mean that SRV compensates for lower VET by increasing HR. PMID- 27378016 TI - Validating the AREDS Simplified Severity Scale of Age-Related Macular Degeneration with 5- and 10-Year Incident Data in a Population-Based Sample. AB - PURPOSE: Most classification systems for age-related macular degeneration (AMD) were developed from patients in clinical trials. We aimed to validate the Age Related Eye Diseases Study (AREDS) simplified severity scale of AMD classification using 5- and 10-year incident late AMD data from the population based Blue Mountains Eye Study (BMES) cohort. DESIGN: Comparative study of population-based cohort and clinical trial. PARTICIPANTS: Blue Mountains Eye Study participants 40 to 97 years of age at baseline (n = 2134) and AREDS participants 55 to 80 years of age (n = 3640). METHODS: In the BMES, AMD lesions were graded from stereoscopic color photographs and were classified according to the AREDS simplified severity scale. The AREDS simplified scale calculates a risk score based on the number of early AMD risk factors (large drusen and pigment abnormalities) in both eyes that can range from 0 to 4. MAIN OUTCOME MEASURES: Five- and 10-year incident late AMD (presence of geographic atrophy or choroidal neovascularization). RESULTS: The AREDS simplified scale performed similarly when applied to both the BMES population-based participants and the AREDS clinical trial-based participants in predicting 5- and 10-year incidence of late AMD. For scores 0 to 4, the 5-year incidence rates for the BMES compared with the AREDS were 0.2% versus 0.4%, 3.1% versus 3.1%, 12.1% versus 11.8%, 13.5% versus 25.9%, and 47.1% versus 47.3%, respectively. The corresponding 10-year incidence rates for the BMES compared with the AREDS were 0.7% versus 1.5%, 7.3% versus 8.4%, 36.6% versus 27.6%, 20.0% versus 52.7%, and 75.0% versus 71.4%, respectively. CONCLUSIONS: The AREDS simplified severity scale classified late AMD risk levels similarly when applied to population-based and clinical trial samples. These results support the robustness of the AREDS simplified severity scale. PMID- 27378017 TI - Network Analysis Implicates Alpha-Synuclein (Snca) in the Regulation of Ovariectomy-Induced Bone Loss. AB - The postmenopausal period in women is associated with decreased circulating estrogen levels, which accelerate bone loss and increase the risk of fracture. Here, we gained novel insight into the molecular mechanisms mediating bone loss in ovariectomized (OVX) mice, a model of human menopause, using co-expression network analysis. Specifically, we generated a co-expression network consisting of 53 gene modules using expression profiles from intact and OVX mice from a panel of inbred strains. The expression of four modules was altered by OVX, including module 23 whose expression was decreased by OVX across all strains. Module 23 was enriched for genes involved in the response to oxidative stress, a process known to be involved in OVX-induced bone loss. Additionally, module 23 homologs were co-expressed in human bone marrow. Alpha synuclein (Snca) was one of the most highly connected "hub" genes in module 23. We characterized mice deficient in Snca and observed a 40% reduction in OVX-induced bone loss. Furthermore, protection was associated with the altered expression of specific network modules, including module 23. In summary, the results of this study suggest that Snca regulates bone network homeostasis and ovariectomy-induced bone loss. PMID- 27378019 TI - Changing patterns in the Epstein-Barr virus (EBV)and Hodgkin lymphoma association in Tunisia. AB - We compared the features of the Epstein-Barr virus (EBV) and Hodgkin lymphoma (HL) association in Tunisia in two periods of time, 1991-2001 (111 cases) and 2002-2012 (122 cases). The investigation of the EBV status by EBER in situ hybridization showed a significant decrease in the prevalence of EBV-positive HL from 69.3 % for the period 1991-2001 to 40.1 % for the 2002-2012 period (p = 0.00001). EBV positivity has decreased in all age groups but was more pronounced among young patients, in the 15-24-year age group (46.1 vs 10.3 %, p = 0.003), in the 25-34-year age group (56.2 vs 25 %, p = 0.04), and among children (88.4 vs 59.2 %, p = 0.01). This decrease in EBV-positive HL over time contrasted with a remarkable increase in EBV-negative HL in young adults aged 15-34 years (51.2 vs 83 %; p = 0.001), especially among women (59.1 vs 91.2 %; p = 0.01). The decrease in EBV-positive HL over time concerns particularly the nodular sclerosis histological subtype (69.2 vs 31.6 %, p = 0.000001). These results indicate that the epidemiology of HL and its association with EBV are changing over time, with a trend toward a Western profile, and point toward the emergence of other environmental causative factors, especially among young women, which remain to be identified. PMID- 27378020 TI - The evolution of offensive realism. AB - Offensive realism, a theory of international relations, holds that states are disposed to competition and conflict because they are self-interested, power maximizing, and fearful of other states. Moreover, it argues that states are obliged to behave this way because doing so favors survival in the international system. Debate continues as to whether modern states actually do, or should, behave in this way, but we are struck by a different question. In this article, we ask whether the three core assumptions about behavior in offensive realism self-help, power maximization, and outgroup fear-have any basis in scientific knowledge about human behavioral evolution. We find that these precise traits are not only evolutionarily adaptive but also empirically common across the animal kingdom, especially in primate and human societies. Based on these findings, we hypothesize that states behave as offensive realists predict not just because of anarchy in the modern international system but also because of the legacy of our evolution. In short, offensive realism may really be describing the nature of the human species more than the nature of the international system. If our hypothesis is correct, then evolutionary theory offers the following: (1) a novel ultimate cause of offensive realist behavior; (2) an extension of offensive realism to any domain in which humans compete for power; and (3) an explanation for why individual leaders themselves, and not just states, seek power. However, a key insight from evolution is that the primacy of self-help, power maximization, and outgroup fear does not necessarily condemn individuals or groups to competition and conflict; rather, these traits can in themselves give rise to cooperation and alliances. PMID- 27378018 TI - Novel multifunctional pH-sensitive nanoparticles loaded into microbubbles as drug delivery vehicles for enhanced tumor targeting. AB - This study fabricated novel multifunctional pH-sensitive nanoparticles loaded into microbubbles (PNP-MB) with the combined advantages of two excellent drug delivery vehicles, namely, pH-sensitive nanoparticles and microbubbles. As an antitumor drug, resveratrol (RES) was loaded into acetylated beta-cyclodextrin nanoparticles (RES-PNP). The drug-loaded nanoparticles were then encapsulated into the internal space of the microbubbles. The characterization and morphology of this vehicle were investigated through dynamic light scattering and confocal laser scanning microscopy, respectively. In vitro drug release was performed to investigate the pH sensitivity of RES-PNP. The antitumor property of RES-loaded PNP-MB (RES-PNP-MB) was also analyzed in vivo to evaluate the antitumor effect of RES-PNP-MB. Results suggested that PNP exhibited pH sensitivity, and was successfully encapsulated into the microbubbles. RES-PNP-MB exhibit effective tumor growth suppressing in vivo. Therefore, such drug delivery vehicle should be of great attention in tumor therapy. PMID- 27378021 TI - Shaking the tyrant's bloody robe. AB - Group violence, despite much study, remains enigmatic. Its forms are numerous, its proximate causes myriad, and the interrelation of its forms and proximate causes poorly understood. We review its evolution, including preadaptations and selected propensities, and its putative environmental and psychological triggers. We then reconsider one of its forms, ethnoreligious violence, in light of recent discoveries in the behavioral and brain sciences. We find ethnoreligious violence to be characterized by identity fusion and by manipulation of religious traditions, symbols, and systems. We conclude by examining the confluence of causes and characteristics before and during Yugoslavia's wars of disintegration. PMID- 27378015 TI - Visual Acuity Loss and Associated Risk Factors in the Retrospective Progression of Stargardt Disease Study (ProgStar Report No. 2). AB - PURPOSE: To examine the association between characteristics of Stargardt disease and visual acuity (VA), to estimate the longitudinal rate of VA loss, and to identify risk factors for VA loss. DESIGN: Retrospective, multicenter cohort study. PARTICIPANTS: A total of 176 patients (332 eyes) with molecularly and clinically confirmed Stargardt disease enrolled from the United States and Europe. METHODS: Standardized data report forms were used to collect retrospective data on participants' characteristics and best-corrected or presenting VA from medical charts. Linear models with generalized estimating equations were used to estimate the cross-sectional associations, and linear mixed effects models were used to estimate the longitudinal VA loss. MAIN OUTCOME MEASURES: Yearly change in VA. RESULTS: The median duration of observation was 3.6 years. At baseline, older age of symptom onset was associated with better VA, and a longer duration of symptoms was associated with worse VA. Longitudinal analysis estimated an average of 0.3 lines loss (P < 0.0001) per year overall, but the rate varied according to baseline VA: (1) eyes with baseline VA >=20/25 (N = 53) declined at a rate of approximately 1.0 line per year; (2) eyes with VA between 20/25 and 20/70 (N = 65) declined at a rate of approximately 0.9 lines per year; (3) eyes with VA between 20/70 and 20/200 (N = 163) declined at a rate of 0.2 lines per year; and (4) eyes with VA worse than 20/200 (n = 49) improved at a rate of 0.5 lines per year. Older age of onset was associated with slower VA loss: Patients with onset age >30 years showed 0.4 lines slower change of VA per year (P = 0.01) compared with patients with onset age <=14 years. CONCLUSIONS: Given the overall slow rate of VA loss, VA is unlikely to be a sensitive outcome measure for treatment trials of Stargardt disease. However, given the faster decline in younger patients and those with no or mild visual impairment, VA may be a potential outcome measure for trials targeting such subgroups of patients. These observations will need to be assessed in a prospective study bearing in mind the inherent limitations of retrospective datasets. PMID- 27378022 TI - Evolutionary institutionalism. AB - BACKGROUND: Institutions are hard to define and hard to study. Long prominent in political science have been two theories: Rational Choice Institutionalism (RCI) and Historical Institutionalism (HI). Arising from the life sciences is now a third: Evolutionary Institutionalism (EI). Comparative strengths and weaknesses of these three theories warrant review, and the value-to-be-added by expanding the third beyond Darwinian evolutionary theory deserves consideration. QUESTION: Should evolutionary institutionalism expand to accommodate new understanding in ecology, such as might apply to the emergence of stability, and in genetics, such as might apply to political behavior? METHODS: Core arguments are reviewed for each theory with more detailed exposition of the third, EI. Particular attention is paid to EI's gene-institution analogy; to variation, selection, and retention of institutional traits; to endogeneity and exogeneity; to agency and structure; and to ecosystem effects, institutional stability, and empirical limitations in behavioral genetics. FINDINGS: RCI, HI, and EI are distinct but complementary. CONCLUSIONS: Institutional change, while amenable to rational-choice analysis and, retrospectively, to criticaljuncture and path-dependency analysis, is also, and importantly, ecological. Stability, like change, is an emergent property of institutions, which tend to stabilize after change in a manner analogous to allopatric speciation. EI is more than metaphorically biological in that institutional behaviors are driven by human behaviors whose evolution long preceded the appearance of institutions themselves. PMID- 27378023 TI - Demographic variation in how the social brain processes news messages. AB - A high capacity for visual perception distinguishes Homo sapiens from other primates. This human ability to detect social cues and retain visual records of social networks has been tested mostly with static facial images in laboratory settings. However, media consumption has become closely entangled with the way social life is navigated. Therefore, the study reported here tested demographic differences (gender and education) in visual information processing of social and nonsocial objects featured in audiovisual news content. Women recognized (accuracy) and recalled (salience) social images better than men. On the other hand, men were more skilled at recognizing, but not recalling, nonsocial images. Participants with lower educational levels recognized and recalled fewer images than individuals with higher educational levels. Interactions between demographic variables and time suggest that memory records for social images are more stable than those for nonsocial images. Memory may have survival-relevant importance, serving navigational functions that vary across environmental demands, resulting in differences across demographic groups. PMID- 27378027 TI - Brain tissue stiffness is a sensitive marker for acidosis. AB - BACKGROUND: Carbon dioxide overdose is frequently used to cull rodents for tissue harvesting. However, this treatment may lead to respiratory acidosis, which potentially could change the properties of the investigated tissue. NEW METHOD: Mechanical tissue properties often change in pathological conditions and may thus offer a sensitive generic readout for changes in biological tissues with clinical relevance. In this study, we performed force-indentation measurements with an atomic force microscope on acute cerebellar slices from adult rats to test if brain tissue undergoes changes following overexposure to CO2 compared to other methods of euthanasia. RESULTS: The pH significantly decreased in brain tissue of animals exposed to CO2. Concomitant with the drop in pH, cerebellar grey matter significantly stiffened. Tissue stiffening was reproduced by incubation of acute cerebellar slices in acidic medium. COMPARISON WITH EXISTING METHODS: Tissue stiffness provides an early, generic indicator for pathophysiological changes in the CNS. Atomic force microscopy offers unprecedented high spatial resolution to detect such changes. CONCLUSIONS: Our results indicate that the stiffness particularly of grey matter strongly correlates with changes of the pH in the cerebellum. Furthermore, the method of tissue harvesting and preparation may not only change tissue stiffness but very likely also other physiologically relevant parameters, highlighting the importance of appropriate sample preparation. PMID- 27378028 TI - Demonstration and validation of a new pressure-based MRI-safe pain tolerance device. AB - BACKGROUND: One of the barriers to studying the behavioral and emotional effects of pain using functional Magnetic Resonance Imaging (fMRI) is the absence of a commercially available, MRI-compatible, pressure-based algometer to elicit pain. The present study sought to address this barrier through creation and validation of a novel MRI-safe apparatus capable of delivering incremental, measurable amounts of pressure inside a scanning bore. NEW METHOD: We introduced an MR-safe device used to administer pressure-based pain. To test against a commercially available, MRI-incompatible algometer (AlgoMed), 199 participants reported their pain tolerance for both devices. A second experiment tested the validity of pressure-based pain in an MRI environment by comparing brain activation with established neural networks for pain. 10 participants performed an identical procedure to test for pain tolerance while being scanned in a 7T MRI scanner. RESULTS: Results support the validity and reliability of our novel device. In Study 1, pain tolerance with this device was strongly correlated with pain tolerance as measured by a commercially available algometer (r=0.78). In Study 2, this device yielded BOLD activation within the insula (BA 13) and anterior cingulate gyrus (BA 24); as pressure increased, activation in these areas parametrically increased. COMPARISON WITH EXISTING METHOD: These findings correspond to other studies using thermal, electrical, or mechanical pain applications. Behavioral and functional data demonstrate that this new device is a valid method of administering pressure-related pain in MRI environments. CONCLUSIONS: Our novel MRI-safe device is a valid instrument to measure and administer pressure-based pain. PMID- 27378029 TI - Sepsis in PD-1 light. AB - Increasing evidence suggests that after the first pro-inflammatory hours, sepsis is characterized by the occurrence of severe immunosuppression. Several mechanisms have been reported to participate in sepsis-induced immune alterations affecting both innate and adaptive immunity. Of these, the concept of 'cell exhaustion' has gained a lot of interest because some parallels can be drawn with the cancer field in which immunostimulation approaches through blocking immune checkpoints currently obtain remarkable success. Herein, perspectives regarding co-inhibitory receptors' contribution to lymphocyte exhaustion in sepsis will be discussed in the context of a recently published study investigating the potential of PD-1 molecule expression (i.e. PD-1 on lymphocytes, PD-L1 on monocytes) to predict mortality in septic shock patients. PMID- 27378030 TI - Re: Radical Prostatectomy or External Beam Radiation Therapy vs No Local Therapy for Survival Benefit in Metastatic Prostate Cancer: A SEER-Medicare Analysis. PMID- 27378031 TI - Comprehensive Proteomic Analysis of Nitrogen-Starved Mycobacterium smegmatis Deltapup Reveals the Impact of Pupylation on Nitrogen Stress Response. AB - Pupylation is a bacterial ubiquitin-like protein modification pathway, which results in the attachment of the small protein Pup to specific lysine residues of cellular targets. Pup was shown to serve as a degradation signal, directing proteins toward the bacterial proteasome for turnover. Recently, it was hypothesized that pupylation and proteasomal protein degradation support the survival of Mycobacterium smegmatis (Msm) during nitrogen starvation by supplying recycled amino acids. In the present study we generated a Pup deletion strain to investigate the influence of pupylation on Msm proteome in the absence of nitrogen sources. Quantitative proteomic analyses revealed a relatively low impact of Pup on MsmDeltapup proteome immediately after exposure to growth medium lacking nitrogen. Less than 5.4% of the proteins displayed altered cellular levels when compared to Msm wild type. In contrast, post 24 h of nitrogen starvation 501 proteins (41% of the total quantified proteome) of Msm pup deletion strain showed significant changes in abundance. Noteworthy, important players involved in nitrogen assimilation were significantly affected in MsmDeltapup. Furthermore, we quantified pupylated proteins of nitrogen-starved Msm to gain more detailed insights in the role of pupylation in surviving and overcoming the lack of nitrogen. PMID- 27378032 TI - Monolayer MoS2 Bandgap Modulation by Dielectric Environments and Tunable Bandgap Transistors. AB - Semiconductors with a moderate bandgap have enabled modern electronic device technology, and the current scaling trends down to nanometer scale have introduced two-dimensional (2D) semiconductors. The bandgap of a semiconductor has been an intrinsic property independent of the environments and determined fundamental semiconductor device characteristics. In contrast to bulk semiconductors, we demonstrate that an atomically thin two-dimensional semiconductor has a bandgap with strong dependence on dielectric environments. Specifically, monolayer MoS2 bandgap is shown to change from 2.8 eV to 1.9 eV by dielectric environment. Utilizing the bandgap modulation property, a tunable bandgap transistor, which can be in general made of a two-dimensional semiconductor, is proposed. PMID- 27378033 TI - Zika virus, women and ethics. PMID- 27378034 TI - Attitudes toward Post-Trial Access to Medical Interventions: A Review of Academic Literature, Legislation, and International Guidelines. AB - There is currently no international consensus around post-trial obligations toward research participants, community members, and host countries. This literature review investigates arguments and attitudes toward post-trial access. The literature review found that academic discussions focused on the rights of research participants, but offered few practical recommendations for addressing or improving current practices. Similarly, there are few regulations or legislation pertaining to post-trial access. If regulatory changes are necessary, we need to understand the current arguments, legislation, and attitudes towards post-trial access and participants and community members. Given that clinical trials conducted in low-income countries will likely continue, there is an urgent need for consideration of post-trial benefits for participants, communities, and citizens of host countries. While this issue may not be as pressing in countries where participants have access to healthcare and medicines through public schemes, it is particularly important in regions where this may not be available. PMID- 27378035 TI - GOLPH3 and oncogenesis: What is the molecular link? AB - The Golgi phosphoprotein 3 (GOLPH3) is encoded by a gene that is located in a region of the human genome that is often amplified in different solid tumours. GOLPH3, an evolutionary conserved phosphatidylinositol 4-phosphate (PI4P) binding protein, is mainly localised at trans Golgi network (TGN). It regulates several cellular functions like Golgi vesicular trafficking, Golgi glycosylation and mitochondrial cardiolipin production. Recently, GOLPH3 was discovered to be part of the DNA damage response signalling pathway, with a role in cell survival following DNA damage. In this review, we will explore the cellular functions regulated by GOLPH3 and discuss if and how they contribute to the oncogenic activity of this intriguing Golgi localized oncoprotein. PMID- 27378036 TI - Ultrastructural and functional characterization of circulating hemocytes from Galleria mellonella larva: Cell types and their role in the innate immunity. AB - Galleria mellonella larvae have been widely used as a model to study the virulence of various human pathogens. Hemocytes play important roles in the innate immune response of G. mellonella. In this study, the hemocytes of G. mellonella larvae were analyzed by transmission electron microscope, light microscope, and cytochemistry. The cytological and morphological analyses revealed four types of hemocytes; Plasmatocytes, granular cells, spherule cells and oenocytoids. Differential hemocyte counts showed that under our conditions plasmatocytes and granular cells were the most abundant circulating cell types in the hemolymph. We also investigated the role of different types of hemocytes in the cellular and humoral immune defenses. The in-vivo experiment showed that plasmatocytes, granular cells and oenocytoids phagocytized FITC-labelled Escherichia coli bacteria in larvae of G. mellonella, whereas the granular cells exhibited the strongest phagocytic ability against these microbial cells. After incubation with L-DOPA, plasmatocytes, granular cells and oenocytoids are stained brown, indicating the presence of phenoloxidase activity. These results shed new light on our understanding of the immune function of G. mellonella hemocytes. PMID- 27378037 TI - Cardiorespiratory Fitness and Risk of Sudden Cardiac Death in Men and Women in the United States: A Prospective Evaluation From the Aerobics Center Longitudinal Study. AB - OBJECTIVES: To examine the relation between cardiorespiratory fitness (CRF) and sudden cardiac death (SCD) in a large US adult population and to study the effects of hypertension, obesity, and health status on the relation of CRF with SCD. PATIENTS AND METHODS: A total of 55,456 individuals (mean age, 44.2 years; 13,507 women) from the Aerobics Center Longitudinal Study, a prospective observational investigation (from January 2, 1974, through December 31, 2002), were included. Cardiorespiratory fitness was assessed by a maximal treadmill test, and baseline assessment included an extensive set of measurements. RESULTS: There were 109 SCDs. An inverse risk of SCD was found across incremental CRF levels after adjusting for potential confounders. Participants with moderate and high CRF levels had 44% (hazard ratio, 0.56; 95% CI, 0.35-0.90) and 48% (hazard ratio, 0.52; 95% CI, 0.30-0.92) significantly lower risk of SCD, respectively, than did those with low CRF levels (P<.001). The risk of SCD decreased by 14% (hazard ratio, 0.86; 95% CI, 0.77-0.96) per 1-metabolic equivalent increase in the fully adjusted model. Hypertensive, overweight, or unhealthy individuals with moderate to high CRF levels had lower risks of SCD (ranging from 58% to 72% of lower risk) than did those with the same medical conditions and low CRF levels. CONCLUSION: The risk of SCD in US men and women could be partially reduced by ensuring moderate to high levels of CRF independently of other risk factors and especially in those who are hypertensive, overweight, or unhealthy. PMID- 27378038 TI - Current Status of Left Ventricular Assist Device Therapy. AB - Congestive heart failure (HF) remains a serious burden in the Western World. Despite advances in pharmacotherapy and resynchronization, many patients have progression to end-stage HF. These patients may be candidates for heart transplant or left ventricular assist device (LVAD) therapy. Heart transplants are limited by organ shortages and in some cases by patient comorbidities; therefore, LVAD therapy is emerging as a strategy of bridge to transplant or as a destination therapy in patients ineligible for transplant. Patients initially ineligible for a transplant may, in certain cases, become eligible for transplant after physiologic improvement with LVAD therapy, and a small number of patients with an LVAD may have sufficient recovery of myocardial function to allow device explantation. This clinically oriented review will describe (1) the most frequently used pump types and aspects of the continuous-flow physiology and (2) the clinical indications for and the shift toward the use of LVADs in less sick patients with HF. Additionally, we review complications of LVAD therapy and project future directions in this field. We referred to the Interagency Registry for Mechanically Assisted Circulatory Support, landmark trials, and results from recently published studies as major sources in obtaining recent outcomes, and we searched for related published literature via PubMed. This review focuses primarily on clinical practice for primary care physicians and non-HF cardiologists in the United States. PMID- 27378039 TI - Pulmonary Sarcoidosis: Diagnosis and Treatment. AB - Sarcoidosis is a chronic granulomatous disease of unknown cause that is seen worldwide and occurs mainly in patients between the ages of 20 and 60 years. It can be difficult to diagnose because it can mimic many other diseases including lymphoproliferative disorders and granulomatous infections and because there is no specific test for diagnosis, which depends on correlation of clinicoradiologic and histopathologic features. This review will focus on recent discoveries regarding the pathogenesis of sarcoidosis, common clinical presentations, diagnostic evaluation, and indications for treatment. This review is aimed largely at general practitioners and emphasizes the importance of differentiating pulmonary sarcoidosis from its common imitators. PMID- 27378040 TI - Risk of Disseminated Disease in Immunosuppressed Patients Receiving Live Zoster Vaccine. PMID- 27378041 TI - In Reply I-Risk of Disseminated Disease in Immunosuppressed Patients Receiving Live Zoster Vaccine. PMID- 27378042 TI - In Reply II-Risk of Disseminated Disease in Immunocompromised Patients Receiving Live Zoster Vaccine. PMID- 27378043 TI - The Different Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Mortality. PMID- 27378044 TI - In Reply-The Different Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Mortality. PMID- 27378045 TI - Decisive Bearing of Organizational Dynamics on the Application and Success of Hospital-Based Cardiac Rehabilitation. PMID- 27378046 TI - Induction of Atrial Fibrillation by Topical Use of Nasal Decongestants. PMID- 27378047 TI - Correction. PMID- 27378048 TI - Multifocal Thoracic Tuberculosis. PMID- 27378049 TI - Malignant Pleural Mesothelioma. PMID- 27378051 TI - Moss Glenn Falls by Mariella Bisson. AB - Recognizing the contribution art has had in the Mayo Clinic environment since the original Mayo Clinic Building was finished in 1914, Mayo Clinic Proceedings features some of the numerous works of art displayed throughout the buildings and grounds on Mayo Clinic campuses as interpreted by the author. PMID- 27378050 TI - Elizabeth Blackburn and Maintenance of Telomeres. PMID- 27378052 TI - Mechanisms of anguilliform locomotion in fishes studied using simple three dimensional physical models. AB - Physical models enable researchers to systematically examine complex and dynamic mechanisms of underwater locomotion in ways that would be challenging with freely swimming animals. Previous research on undulatory locomotion, for example, has used rectangular flexible panels that are effectively two-dimensional as proxies for the propulsive surfaces of swimming fishes, but these bear little resemblance to the bodies of elongate eel-like swimming animals. In this paper we use a polyurethane rod (round cross-section) and bar (square cross-section) to represent the body of a swimming Pacific hagfish (Eptatretus stoutii). We actuated the rod and bar in both heave and pitch using a mechanical controller to generate a propulsive wave at frequencies between 0.5 and 2.5 Hz. We present data on (1) how kinematic swimming patterns change with driving frequency in these elongate fish-like models, (2) the thrust-generating capability of these simple models, (3) how forces and work done during propulsion compare between cross sectional shapes, (4) the wake flow patterns in these swimming models using particle image velocimetry. We also contrast kinematic and hydrodynamic patterns produced by bar and rod models to comparable new experimental data on kinematics and wake flow patterns from freely swimming hagfish. Increasing the driving frequency of bar and rod models reduced trailing edge amplitude and wavelength, and above 2 Hz a nodal point appeared in the kinematic wave. Above 1 Hz, both the rod and bar generated net thrust, with the work per cycle reaching a minimum at 1.5 Hz, and the bar always requiring more work per cycle than the rod. Wake flow patterns generated by the swimming rod and bar included clearly visible lateral jets, but not the caudolaterally directed flows seen in the wakes from freely swimming hagfish. PMID- 27378053 TI - Determination of a Testing Threshold for Lumbar Puncture in the Diagnosis of Subarachnoid Hemorrhage after a Negative Head Computed Tomography: A Decision Analysis. AB - OBJECTIVE: The objective was to determine the testing threshold for lumbar puncture (LP) in the evaluation of aneurysmal subarachnoid hemorrhage (SAH) after a negative head computed tomography (CT). As a secondary aim we sought to identify clinical variables that have the greatest impact on this threshold. METHODS: A decision analytic model was developed to estimate the testing threshold for patients with normal neurologic findings, being evaluated for SAH, after a negative CT of the head. The testing threshold was calculated as the pretest probability of disease where the two strategies (LP or no LP) are balanced in terms of quality-adjusted life-years. Two-way and probabilistic sensitivity analyses (PSAs) were performed. RESULTS: For the base-case scenario the testing threshold for performing an LP after negative head CT was 4.3%. Results for the two-way sensitivity analyses demonstrated that the test threshold ranged from 1.9% to 15.6%, dominated by the uncertainty in the probability of death from initial missed SAH. In the PSA the mean testing threshold was 4.3% (95% confidence interval = 1.4% to 9.3%). Other significant variables in the model included probability of aneurysmal versus nonaneurysmal SAH after negative head CT, probability of long-term morbidity from initial missed SAH, and probability of renal failure from contrast-induced nephropathy. CONCLUSIONS: Our decision analysis results suggest a testing threshold for LP after negative CT to be approximately 4.3%, with a range of 1.4% to 9.3% on robust PSA. In light of these data, and considering the low probability of aneurysmal SAH after a negative CT, classical teaching and current guidelines addressing testing for SAH should be revisited. PMID- 27378054 TI - A study on the predictors of Korean male students' intention to receive human papillomavirus vaccination. AB - AIMS AND OBJECTIVES: The objective was to survey the current state of human papillomavirus (HPV) vaccination and the predictors of vaccination intention among Korean male students of high school (ages 15-19) and university (ages 17 27). BACKGROUND: Human papillomavirus is a sexually transmitted infectious agent causing uterine cervical, anal, and/or penile cancer and genital warts in males and females. Infection rate of human papillomavirus increases from the age when sexual intercourse first occurs. Therefore, motivation to receive human papillomavirus vaccination is needed to protect infection. DESIGN: Cross sectional descriptive survey was performed only in male students. They are less aware of human papillomavirus than females, because human papillomavirus vaccination has been targeted on females for preventing cervical cancer in Korea. METHODS: Data were collected using a self-reporting questionnaire for male high school and university students sampled from a city in Korea. Human papillomavirus vaccine-related knowledge, health beliefs, demographic, and sexual history information variables relating to intentions to vaccinate were assessed. RESULTS: The human papillomavirus vaccination rate was very low and the levels of knowledge and health beliefs were low. The significant predictors that raised the intention of human papillomavirus vaccination were a university student, experience of sexual intercourse and perceiving the benefits of human papillomavirus vaccination. CONCLUSIONS: To promote human papillomavirus vaccination, educational programming targeting males should include health beliefs and knowledge, emphasising that vaccination is important to prevent uterine cervical cancer and to role as a preventative measure against common male diseases. RELEVANCE TO CLINICAL PRACTICE: Male high school students should be included as a major target population for school human papillomavirus education programmes, as they are at the age of commencing sexual intercourse. In addition, public health policies including human papillomavirus vaccination in the national immunisation programme are warranted. PMID- 27378056 TI - Les Syndromes De Malabsorption. PMID- 27378057 TI - Selected Summaries. PMID- 27378055 TI - Comparative genomic analysis of novel Acinetobacter symbionts: A combined systems biology and genomics approach. AB - The increasing trend of antibiotic resistance in Acinetobacter drastically limits the range of therapeutic agents required to treat multidrug resistant (MDR) infections. This study focused on analysis of novel Acinetobacter strains using a genomics and systems biology approach. Here we used a network theory method for pathogenic and non-pathogenic Acinetobacter spp. to identify the key regulatory proteins (hubs) in each strain. We identified nine key regulatory proteins, guaA, guaB, rpsB, rpsI, rpsL, rpsE, rpsC, rplM and trmD, which have functional roles as hubs in a hierarchical scale-free fractal protein-protein interaction network. Two key hubs (guaA and guaB) were important for insect-associated strains, and comparative analysis identified guaA as more important than guaB due to its role in effective module regulation. rpsI played a significant role in all the novel strains, while rplM was unique to sheep-associated strains. rpsM, rpsB and rpsI were involved in the regulation of overall network topology across all Acinetobacter strains analyzed in this study. Future analysis will investigate whether these hubs are useful as drug targets for treating Acinetobacter infections. PMID- 27378059 TI - Highly luminescent S,N co-doped carbon quantum dots-sensitized chemiluminescence on luminol-H2 O2 system for the determination of ranitidine. AB - S,N co-doped carbon quantum dots (N,S-CQDs) with super high quantum yield (79%) were prepared by the hydrothermal method and characterized by transmission electron microscopy, photoluminescence, UV-Vis spectroscopy and Fourier transformed infrared spectroscopy. N,S-CQDs can enhance the chemiluminescence intensity of a luminol-H2 O2 system. The possible mechanism of the luminol-H2 O2 (N,S-CQDs) was illustrated by using chemiluminescence, photoluminescence and ultraviolet analysis. Ranitidine can quench the chemiluminescence intensity of a luminol-H2 O2 -N,S-CQDs system. So, a novel flow-injection chemiluminescence method was designed to determine ranitidine within a linear range of 0.5-50 MUg ml-1 and a detection limit of 0.12 MUg ml-1 . The method shows promising application prospects. PMID- 27378060 TI - Single spin magnetic resonance. AB - Different approaches have improved the sensitivity of either electron or nuclear magnetic resonance to the single spin level. For optical detection it has essentially become routine to observe a single electron spin or nuclear spin. Typically, the systems in use are carefully designed to allow for single spin detection and manipulation, and of those systems, diamond spin defects rank very high, being so robust that they can be addressed, read out and coherently controlled even under ambient conditions and in a versatile set of nanostructures. This renders them as a new type of sensor, which has been shown to detect single electron and nuclear spins among other quantities like force, pressure and temperature. Adapting pulse sequences from classic NMR and EPR, and combined with high resolution optical microscopy, proximity to the target sample and nanoscale size, the diamond sensors have the potential to constitute a new class of magnetic resonance detectors with single spin sensitivity. As diamond sensors can be operated under ambient conditions, they offer potential application across a multitude of disciplines. Here we review the different existing techniques for magnetic resonance, with a focus on diamond defect spin sensors, showing their potential as versatile sensors for ultra-sensitive magnetic resonance with nanoscale spatial resolution. PMID- 27378061 TI - Eradication of methicillin resistant Staphylococcus aureus detected for the first time in cystic fibrosis: A single center observational study. AB - OBJECTIVE: To retrospectively identify CF patients with methicillin resistant Staphylococcus aureus (MRSA) and to assess the long-term success of an eradication scheme introduced in 2002 for all newly colonized patients. PATIENTS: All microbiological results from all 505 CF patients followed between 2002 and 2012 were analyzed focusing on the detection of MRSA. METHODS: Retrospective patient record analysis of MRSA positive CF patients regarding eradication and clinical outcome. RESULTS: We identified 57 patients with MRSA, mean age 15.3 years (range: 0.6-36.9, incidence 0.9%/year). Of these, nine patients were lost to follow-up; seven chronically colonized patients were excluded from the intervention. Eradication was suggested to all patients, 37/41 gave their consent to the following two-step approach: (i) dual iv antibiotic treatment over 3 weeks, accompanied by hygienic directives and topical therapy for 5 days followed by a 6-week period with dual oral antibiotic therapy and inhalation with vancomycin. (ii) Each new MRSA detection was treated with 6 weeks inhalation of vancomycin and topical therapy for 5 days. Long-term eradication was rated by the microbiological status in the third year after first detection. MRSA was eradicated in 31 of 37 patients (84%) whose clinical course was stable (mean FEV1 one year before MRSA 80.4%, 3 years after MRSA 81.0%). CONCLUSIONS: MRSA colonization mandates complex and expensive hygienic measures which are not well accepted by patients. Therefore, MRSA eradication is desirable. Intensive therapy regimens may be successful in patients with CF and might help to maintain a stable clinical course. Pediatr Pulmonol. 2016;51:1010-1019. (c) 2016 Wiley Periodicals, Inc. PMID- 27378062 TI - Inactive rhomboid proteins: New mechanisms with implications in health and disease. AB - Rhomboids, proteases containing an unusual membrane-integral serine protease active site, were first identified in Drosophila, where they fulfill an essential role in epidermal growth factor receptor signaling, by cleaving membrane-tethered growth factor precursors. It has recently become apparent that eukaryotic genomes harbor conserved catalytically inactive rhomboid protease homologs, including derlins and iRhoms. Here we highlight how loss of proteolytic activity was followed in evolution by impressive functional diversification, enabling these pseudoproteases to fulfill crucial roles within the secretory pathway, including protein degradation, trafficking regulation, and inflammatory signaling. We distil the current understanding of the roles of rhomboid pseudoproteases in development and disease. Finally, we address mechanistically how versatile features of proteolytically active rhomboids have been elaborated to serve the sophisticated functions of their pseudoprotease cousins. By comparing functional and structural clues, we highlight common principles shared by the rhomboid superfamily, and make mechanistic predictions. PMID- 27378063 TI - The role of apelin in central cardiovascular regulation in rats with post-infarct heart failure maintained on a normal fat or high fat diet. AB - Based on the available literature, it can be assumed that in cases of post infarct heart failure (HF) and obesity, a significant change in the central regulation of the cardiovascular system takes place with, among others, the involvement of the apelinergic system. The main objective of the present study was to clarify the role of apelin-13 in the central regulation of the cardiovascular system in Sprague Dawley rats with HF or sham operated (SO) and fed on a normal fat (NFD) or a high fat diet (HFD). The study was divided into two parts: Part I, hemodynamic studies; and Part II, biochemical and molecular studies. The animals were subjected to the following research procedures. Part I and II: feeding NFD or HFD; experimental induction of HF or SO; Part I: intracerebroventricular (ICV) infusion of the examined substances, monitoring of mean arterial blood pressure (MABP) and heart rate (HR); Part II: venous blood and tissue samples collected. ICV infusion of apelin-13 caused significantly higher changes in DeltaMABP in the SO NFD group. No changes were noted in DeltaHR in any of the studied groups. Apelin and apelin receptor (APJ) mRNA expression in the brain and adipose tissues was higher in the HF rats. HFD causes significant increase in expression of apelin and APJ mRNA in the left ventricle. In conclusion, HF and HFD appear to play an important role in modifying the activity of the central apelinergic system and significant changes in mRNA expression of apelin and APJ receptor. PMID- 27378064 TI - Mandibular dysostosis without microphthalmia caused by OTX2 deletion. AB - Mutations in OTX2 are mostly identified in patients with anophthalmia/microphthalmia with variable severity. The OTX2 homeobox gene plays a crucial role in craniofacial morphogenesis during early embryo development. We report for the first time a patient with a mandibular dysostosis caused by a 120 kb deletion including the entire coding sequence of OTX2, identified by array CGH. No ocular malformations were identified after extended ophthalmologic examination. Our data refine the clinical spectrum associated with OTX2 mutations and suggests that OTX2 haploinsufficiency should be considered as a possible cause for isolated mandibular dysostosis. (c) 2016 Wiley Periodicals, Inc. PMID- 27378065 TI - Targeting health care in armed conflicts and emergencies: is it underestimated? PMID- 27378066 TI - The LZIP: A Bayesian latent factor model for correlated zero-inflated counts. AB - Motivated by a study of molecular differences among breast cancer patients, we develop a Bayesian latent factor zero-inflated Poisson (LZIP) model for the analysis of correlated zero-inflated counts. The responses are modeled as independent zero-inflated Poisson distributions conditional on a set of subject specific latent factors. For each outcome, we express the LZIP model as a function of two discrete random variables: the first captures the propensity to be in an underlying "at-risk" state, while the second represents the count response conditional on being at risk. The latent factors and loadings are assigned conditionally conjugate gamma priors that accommodate overdispersion and dependence among the outcomes. For posterior computation, we propose an efficient data-augmentation algorithm that relies primarily on easily sampled Gibbs steps. We conduct simulation studies to investigate both the inferential properties of the model and the computational capabilities of the proposed sampling algorithm. We apply the method to an analysis of breast cancer genomics data from The Cancer Genome Atlas. PMID- 27378067 TI - The hydrodynamics of bubble rise and impact with solid surfaces. AB - A bubble smaller than 1mm in radius rises along a straight path in water and attains a constant speed due to the balance between buoyancy and drag force. Depending on the purity of the system, within the two extreme limits of tangentially immobile or mobile boundary conditions at the air-water interface considerably different terminal speeds are possible. When such a bubble impacts on a horizontal solid surface and bounces, interesting physics can be observed. We study this physical phenomenon in terms of forces, which can be of colloidal, inertial, elastic, surface tension and viscous origins. Recent advances in high speed photography allow for the observation of phenomena on the millisecond scale. Simultaneous use of such cameras to visualize both rise/deformation and the dynamics of the thin film drainage through interferometry are now possible. These experiments confirm that the drainage process obeys lubrication theory for the spectrum of micrometre to millimetre-sized bubbles that are covered in this review. We aim to bridge the colloidal perspective at low Reynolds numbers where surface forces are important to high Reynolds number fluid dynamics where the effect of the surrounding flow becomes important. A model that combines a force balance with lubrication theory allows for the quantitative comparison with experimental data under different conditions without any fitting parameter. PMID- 27378068 TI - Selective protein complexation and coacervation by polyelectrolytes. AB - This review discusses the possible relationship between protein charge anisotropy, protein binding affinity, polymer structure, and selective phase separation. We hope that a fundamental understanding of primarily electrostatically driven protein-polyelectrolyte (PE) interactions can enable the prediction of selective protein binding, and hence selective coacervation through non-specific electrostatics. Such research will partially challenge the assumption that specific binding has to be realized through specific binding sites with a variety of short-range interactions and some geometric match. More specifically, the recent studies on selective binding of proteins by polyelectrolytes were examined from different assemblies in addition to the electrostatic features of proteins and PEs. At the end, the optimization of phase separation based on binding affinity for selective coacervation and some considerations relevant to using PEs for protein purification were also overviewed. PMID- 27378069 TI - Chirality in a quaternionic representation of the genetic code. AB - A quaternionic representation of the genetic code, previously reported by the authors (BioSystems 141 (10-19), 2016), is updated in order to incorporate chirality of nucleotide bases and amino acids. The original representation associates with each nucleotide base a prime integer quaternion of norm 7 and involves a function that assigns to each codon, represented by three of these quaternions, another integer quaternion (amino acid type quaternion). The assignation is such that the essentials of the standard genetic code (particularly its degeneration) are preserved. To show the advantages of such a quaternionic representation we have designed an algorithm to go from the primary to the tertiary structure of the protein. The algorithm uses, besides of the type quaternions, a second kind of quaternions with real components that we additionally associate with the amino acids according to their order along the proteins (order quaternions). In this context, we incorporate chirality in our representation by observing that the set of eight integer quaternions of norm 7 can be partitioned into a pair of subsets of cardinality four each with their elements mutually conjugate and by putting them into correspondence one to one with the two sets of enantiomers (D and L) of the four nucleotide bases adenine, cytosine, guanine and uracil, respectively. We then propose two diagrams in order to describe the hypothetical evolution of the genetic codes corresponding to both of the chiral systems of affinities: D-nucleotide bases/L-amino acids and L nucleotide bases/D-amino acids at reading frames 5'->3' and 3'->5', respectively. Guided by these diagrams we define functions that in each case assign to the triplets of D- (L-) bases a L- (D-) amino acid type integer quaternion. Specifically, the integer quaternion associated with a given D-amino acid is the conjugate of that one corresponding to the enantiomer L. The chiral type quaternions obtained for the amino acids are used, together with a common set of order quaternions, to describe the folding of the two classes, L and D, of homochiral proteins. PMID- 27378070 TI - Graphene-Coated ZnO and SiO2 as Supports for CoO Nanoparticles with Enhanced Reducibility. AB - The insertion of a graphene layer between cobalt and a substrate modifies the morphology and the oxidation/reduction properties of supported cobalt particles. Co forms a relatively flat structure on ZnO and SiO2 , whereas individual Co nanoparticles are formed after graphene coating of these substrates. The graphene layer moderates the formation of cobalt oxide in 5*10-7 mbar O2 and promotes the reduction of oxidized Co in H2 at lower temperature. Angle-resolved XPS measurements indicate that this is mainly a consequence of the restricted interaction of cobalt with the oxide supports. After the low-pressure redox treatments, the graphene layer maintains a relatively high quality with a small number of defect sites. PMID- 27378072 TI - Analytical Chemistry and Our National Science Initiatives. PMID- 27378071 TI - Startle amplitude during unpleasant pictures is greater in veterans with a history of multiple-suicide attempts and predicts a future suicide attempt. AB - Recent studies demonstrate that veterans exhibit higher suicide risk compared with the general U.S. POPULATION: A prior suicide attempt is a well-documented predictor of suicide death. Despite increased attention to clinical risk factors of suicide and efforts to develop psychosocial interventions to reduce suicide risk, the underlying biological factors that confer this risk are not well understood. This study examined affect-modulated startle (AMS) during a series of intermixed unpleasant, neutral, and pleasant pictures in a sample of 108 demographically-matched veterans at low (passive ideators: n = 26) and high risk (active ideators: n = 29; single attempters: n = 28; and multiple attempters: n = 25) for suicide based on the Columbia Suicide Severity Rating Scale. An exploratory aim involved a longitudinal component in a subset of the high-risk sample that went on to participate in a randomized 6-month clinical trial. We investigated whether baseline AMS predicts a subsequent suicide attempt at 12 month follow-up. Compared with the other three groups, multiple attempters showed greater startle potentiation during unpleasant pictures and deficient overall startle habituation from early to later trials. The groups did not differ in startle during neutral or pleasant pictures, or self-reported picture valence. Greater startle during unpleasant pictures was associated with greater emotion dysregulation as measured by the Difficulties in Emotion Regulation Scale and a future suicide attempt assessed prospectively at 12-month follow-up. These findings suggest that startle potentiation during unpleasant pictures in multiple suicide attempters is a promising psychophysiological biomarker of suicide risk and underscore the clinical importance of targeting emotion dysregulation in the treatment of patients at-risk for suicide. PMID- 27378073 TI - Particle-directed assembly of semiflexible polymer chains. AB - We use Langevin dynamics simulations to study aggregation of semiflexible polymers driven by attractions between polymers and spherical particles. We consider a simple model with purely repulsive polymer/polymer and particle/particle interactions but attractive polymer/particle interactions. We find a rich "phase diagram" that contains several different types of globular and rod-like aggregates with either liquid-like or crystalline structure for the particle positions. Systems that exhibit rod-like aggregates with crystalline internal order exhibit a discontinuous rod-globule transition, while systems with liquid-like internal order exhibit a smooth crossover between isotropic and elongated aggregates with increasing chain stiffness. Polymers in elongated liquid-like aggregates often adopt helical configurations that wind around the axis of the aggregate. PMID- 27378075 TI - In vitro membrane stabilizing, thrombolytic and antioxidant potentials of Drynaria quercifolia L., a remedial plant of the Garo tribal people of Bangladesh. AB - BACKGROUND: Drynaria quercifolia L. (Family- Polypodiaceae) is a fern grows in Bangladesh used in traditional healing by the Garo tribe of Mymensingh district. In the current study, rhizomes and fertile foliage fronds of this plant have been investigated comprehensively to assess their in vitro membrane stabilizing, thrombolytic and antioxidant properties. METHODS: Rhizomes and fertile foliage fronds of D. quercifolia were collected, dried, powdered and extracted with methanol. Later on, crude methanol extracts of the plant parts were fractionated into petroleum ether, carbon tetrachloride, chloroform and aqueous soluble fractions. The extractives were then subjected to membrane stabilizing, thrombolytic and antioxidant assays. RESULTS: In membrane stabilizing assay, crude methanol extracts of rhizomes and fertile foliage fronds and their petroleum ether fractions were found to be very effective for stabilizing erythrocyte membrane in hypotonic solution. In case of thrombolytic study, crude methanol extract of rhizomes and its aqueous fraction exhibited noticeable clot lysis. However, in antioxidant assays, crude methanol extracts of the tested plant parts and their aqueous fractions exhibited potent 1,1-diphenyl-2 picrylhydrazyl (DPPH), hydrogen peroxide and 2, 2'-azinobis (3 ethylbenzothiazoline sulphonic acid) (ABTS) radical scavenging activity. Besides, these extractives also displayed substantial ferric reducing potential in ferric reducing antioxidant power (FRAP) assay. Crude methanol extracts of the plant parts and their aqueous fractions were also found rich in phenolics. CONCLUSION: This study demonstrates the medicinal potentials of D. quercifolia and justifies the local uses of it by the Garo tribal people of Bangladesh for multiple disease management. PMID- 27378074 TI - Loss of histone deacetylase HDAC1 induces cell death in Drosophila epithelial cells through JNK and Hippo signaling. AB - Inactivation of HDAC1 and its homolog HDAC2 or addition of HDAC inhibitors in mammalian systems induces apoptosis, cell cycle arrest, and developmental defects. Although these phenotypes have been extensively characterized, the precise underlying mechanisms remain unclear, particularly in in vivo settings. In this study, we show that inactivation of Rpd3, the only HDAC1 and HDAC2 ortholog in Drosophila, induced apoptosis and clone elimination in the developing eye and wing imaginal discs. Depletion of Rpd3 by RNAi cell-autonomously increased JNK activities and decreased activities of Yki, the nuclear effecter of Hippo signaling pathway. In addition, inhibition of JNK activities largely rescued Rpd3 RNAi-induced apoptosis, but did not affect its inhibition of Yki activities. Conversely, increasing the Yki activities largely rescued Rpd3 RNAi induced apoptosis, but did not affect its induction of JNK activities. Furthermore, inactivation of Mi-2, a core component of the Rpd3-containing NuRD complex strongly induced JNK activities; while inactivation of Sin3A, a key component of the Rpd3-containing Sin3 complex, significantly inhibited Yki activities. Taken together, these results reveal that inactivation of Rpd3 independently regulates JNK and Yki activities and that both Hippo and JNK signaling pathways contribute to Rpd3 RNAi-induced apoptosis. PMID- 27378076 TI - Genomics-informed isolation and characterization of a symbiotic Nanoarchaeota system from a terrestrial geothermal environment. AB - Biological features can be inferred, based on genomic data, for many microbial lineages that remain uncultured. However, cultivation is important for characterizing an organism's physiology and testing its genome-encoded potential. Here we use single-cell genomics to infer cultivation conditions for the isolation of an ectosymbiotic Nanoarchaeota ('Nanopusillus acidilobi') and its host (Acidilobus, a crenarchaeote) from a terrestrial geothermal environment. The cells of 'Nanopusillus' are among the smallest known cellular organisms (100-300 nm). They appear to have a complete genetic information processing machinery, but lack almost all primary biosynthetic functions as well as respiration and ATP synthesis. Genomic and proteomic comparison with its distant relative, the marine Nanoarchaeum equitans illustrate an ancient, common evolutionary history of adaptation of the Nanoarchaeota to ectosymbiosis, so far unique among the Archaea. PMID- 27378077 TI - Adolescents' ratings of features of parks that encourage park visitation and physical activity. AB - BACKGROUND: The neighbourhood environment such as the availability of parks are a key, but under-researched, influence on adolescents' physical activity. In addition to overall physical activity levels, park-based physical activity and park visitation is low in this age group. Thus, it is critical to identify park features that may encourage or discourage adolescents from visiting parks. This study used a novel methodology to identify key physical characteristics of parks that are perceived to be important for park visitation and park-based physical activity among adolescents. METHODS: Four secondary schools located in low, mid and high socio-economic status areas of Victoria, Australia were recruited. Using a purpose-built computer application, students in years 8-10 were presented with 44 original photographic images of park features. Participants rated each image (range 1-10) on how likely the feature would be to encourage them to visit a park and to engage in park-based physical activity, and placed symbols ('thumbs up'/'thumbs down') on aspects of the image that had a positive or negative influence on their ratings. RESULTS: Participants (n = 99) had a mean age of 13.3 years (SD = 0.87) and 53% were female. Overall, the top three rated images prompting park visitation by adolescents were: a long steep slide, a flying fox and a table tennis table. These first two features were also reported as being likely to promote physical activity in the park. Differences in ratings were observed for boys and girls. The images that received the greatest number of "thumbs-up" symbols included large swings and slides, table tennis tables, no smoking signs, flying foxes and BMX tracks. The images that received the greatest number of "thumbs-down" symbols included signage about rules, graffiti, toilets, concrete steps, and skate bowls. CONCLUSION: Physically challenging play equipment is likely to encourage adolescents to visit and be active in parks. Rules, graffiti, toilets and skate bowls may discourage visitation. It is important for park designers, planners and policy makers to consider adolescents' views of what park design features are important so that parks are created that support and encourage visitation and optimise levels of physical activity when in the park. PMID- 27378078 TI - Cetuximab-induced aseptic meningitis: case report and review of a rare adverse event. AB - BACKGROUND: Cetuximab is a commonly used antibody agent in the treatment of colorectal or head and neck cancer. Although it is generally well tolerated in most patients, cetuximab has been associated with some rare but serious adverse events. Aseptic meningitis is one such distinctly uncommon adverse drug reaction. CASE PRESENTATION: We present the case of a middle-aged Caucasian patient, who presented with fever and headache within a few hours of starting cetuximab therapy and was diagnosed with cetuximab-induced aseptic meningitis after a complete workup. CONCLUSION: To our knowledge, this is the ninth case of cetuximab-induced aseptic meningitis reported in literature. Because of a nonspecific clinical presentation, this adverse drug reaction can be easily misdiagnosed. It is important to increase awareness of this potentially severe reaction among oncologists. PMID- 27378079 TI - Unmet information needs and limited health literacy in newly diagnosed breast cancer patients over the course of cancer treatment. AB - OBJECTIVE: To investigate unmet information needs in newly diagnosed breast cancer patients over the course of cancer treatment and its association with health literacy. METHODS: We present results from a prospective, multicenter cohort study (PIAT). Newly diagnosed breast cancer patients (N=1060) were surveyed directly after breast cancer surgery, 10 and 40 weeks later. Pooled linear regression modeling was employed analyzing changes in unmet information needs over time and its association with health literacy. RESULTS: Unmet information needs on side effects and medication and medical examination results and treatment options were high and increased during the first 10 weeks after breast cancer surgery. Considering health promotion and social issues, unmet information needs started high and decreased during post-treatment. Patients with limited health literacy had higher unmet information needs. CONCLUSION: Our results indicate a mismatch in information provision and breast cancer patients' information needs. Patients with limited health literacy may be at a distinct disadvantage in having their information needs met over the course of breast cancer treatment. PRACTICE IMPLICATIONS: Strategies are needed to reduce unmet information needs in breast cancer patients considering treatment-phase and health literacy and thereby enable them to better cope with their diseases. PMID- 27378080 TI - A qualitative exploration of favorite patients in primary care. AB - OBJECTIVE: To ascertain whether physicians have favorite patients, their experiences with such patients, and how such relationships may influence patients and physicians. METHODS: Semi-structured key informant interviews with 25 primary care internists practicing in several clinic settings at a large academic medical center. RESULTS: The term 'favorite patient' raised concerns regarding boundaries and favoritism. Nevertheless, most participants (22/25) reported having favorite patients. For many physicians, favorite patients were not necessarily the most compliant patients, or those most similar to them. Instead, favorite patients were often very sick patients and/or those who have known their physicians for a long time. Many of these relationships were defined by experiences that strengthened the patient-physician bond. Participants felt that the favorite patient bond had a positive effect on patients and physicians ("it improves my day"). Physicians also discussed their challenging patients unprompted. Participants voiced that being cognizant of having favorite and challenging patients help to prevent favoring the care of certain patients over others. CONCLUSIONS & PRACTICE IMPLICATIONS: Primary care physicians value patient relationships and benefit from deep bonds. A better understanding of how favorite patients affect primary care physicians could help inform and improve relationships with all patients. PMID- 27378081 TI - Determinants of antihypertensive adherence among patients in Beijing: Application of the health belief model. AB - OBJECTIVES: This study was aimed to determine the factors associated with antihypertensive adherence based on the Health Belief Model (HBM). METHODS: A cross-sectional study was conducted in a rural area of China in 2014. The questionnaire included information about demographics, a scale based on the HBM, and the four-item Morisky Medication Adherence Scale. RESULTS: 745 hypertensive patients participated in the study (345 men, 400 women). Patients' mean age was 56.4+/-10.8years. The prevalence of adherence was 43.5%. Structural equation modeling showed that men, older participants, and those with greater knowledge of hypertension showed better medication adherence than did other participants. Based on the HBM, higher levels of self-efficacy and perceived severity and a lower level of perceived barriers were associated with better antihypertensive adherence. Self-efficacy was one of the most important mediating variables affecting antihypertensive adherence. CONCLUSIONS: Antihypertensive adherence was not optimal among patients in Beijing. Given that many factors are associated with medication adherence, individualized intervention strategies should be carried out in Beijing, China, especially in community settings. PRACTICE IMPLICATIONS: Medication adherence can be improved by enhancing patients' self efficacy because it was the most important influence and mediating variable. PMID- 27378082 TI - Structural studies of N-terminal mutants of Connexin 26 and Connexin 32 using (1)H NMR spectroscopy. AB - Alterations in gap junctions underlie the etiologies of syndromic deafness (KID) and Charcot-Marie Tooth disease (CMTX). Functional gap junctions are composed of connexin molecules with N-termini containing a flexible turn around G12, inserting the N-termini into the channel pore allowing voltage gating. The loss of this turn correlates with loss of Connexin 32 (Cx32) function by impaired trafficking to the cell membrane. Using (1)H NMR we show the N-terminus of a syndromic deafness mutation Cx26G12R, producing "leaky channels", contains a turn around G12 which is less structured and more flexible than wild-type. In contrast, the N-terminal structure of the same mutation in Cx32 chimera, Cx32*43E1G12R shows a larger constricted turn and no membrane current expression but forms membrane inserted hemichannels. Their function was rescued by formation of heteromeric channels with wild type subunits. We suggest the inflexible Cx32G12R N-terminus blocks ion conduction in homomeric channels and this channel block is relieved by incorporation of wild type subunits. In contrast, the increased open probability of Cx26G12R hemichannels is likely due to the addition of positive charge in the channel pore changing pore electrostatics and impairing hemichannel regulation by Ca(2+). These results provide mechanistic information on aberrant channel activity observed in disease. PMID- 27378083 TI - Transmembrane dynamics of the Thr-5 phosphorylated sarcolipin pentameric channel. AB - Sarcolipin (SLN), an important membrane protein expressed in the sarcoplasmic reticulum (SR), regulates muscle contractions in cardiac and skeletal muscle. The phosphorylation at amino acid Thr5 of the SLN protein modulates the amount of Ca(2+) that passes through the SR. Using molecular dynamics simulation, we evaluated the phosphorylation at Thr5 of pentameric SLN (phospho-SLN) channel's energy barrier and pore characteristics by calculating the potential of mean force (PMF) along the channel pore and determining the diffusion coefficient. The results indicate that pentameric phospho-SLN promotes penetration of monovalent and divalent ions through the channel. The analysis of PMF, pore radius and diffusion coefficient indicates that Leu21 is the hydrophobic gate of the pentameric SLN channel. In the channel, water molecules near the Leu21 pore demonstrated a clear hydrated-dehydrated transition; however, the mutation of Leu21 to an Alanine (L21A) destroyed the hydrated-dehydrated transitions. These water-dynamic behaviors and PMF confirm that Leu21 is the key residue that regulates the ion permeability of the pentameric SLN channel. These results provide the structural-basis insights and molecular-dynamic information that are needed to understand the regulatory mechanisms of ion permeability in the pentameric SLN channel. PMID- 27378084 TI - Clinical tool for predicting survival in ALS: do we need one? PMID- 27378085 TI - A clinical tool for predicting survival in ALS. AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and usually fatal neurodegenerative disease. Survival from diagnosis varies considerably. Several prognostic factors are known, including site of onset (bulbar or limb), age at symptom onset, delay from onset to diagnosis and the use of riluzole and non-invasive ventilation (NIV). Clinicians and patients would benefit from a practical way of using these factors to provide an individualised prognosis. METHODS: 575 consecutive patients with incident ALS from a population-based registry in South-East England register for ALS (SEALS) were studied. Their survival was modelled as a two-step process: the time from diagnosis to respiratory muscle involvement, followed by the time from respiratory involvement to death. The effects of predictor variables were assessed separately for each time interval. FINDINGS: Younger age at symptom onset, longer delay from onset to diagnosis and riluzole use were associated with slower progression to respiratory involvement, and NIV use was associated with lower mortality after respiratory involvement, each with a clinically significant effect size. Riluzole may have a greater effect in younger patients and those with longer delay to diagnosis. A patient's survival time has a roughly 50% chance of falling between half and twice the predicted median. INTERPRETATION: A simple and clinically applicable graphical method of predicting an individual patient's survival from diagnosis is presented. The model should be validated in an independent cohort, and extended to include other important prognostic factors. PMID- 27378086 TI - NCRI phase II study of CHOP in combination with ofatumumab in induction and maintenance in newly diagnosed Richter syndrome. AB - Richter syndrome (RS) is associated with chemotherapy resistance and a poor historical median overall survival (OS) of 8-10 months. We conducted a phase II trial of standard CHOP-21 (cyclophosphamide, doxorubicin, vincristine, prednisolone every 21 d) with ofatumumab induction (Cycle 1: 300 mg day 1, 1000 mg day 8, 1000 mg day 15; Cycles 2-6: 1000 mg day 1) (CHOP-O) followed by 12 months ofatumumab maintenance (1000 mg given 8-weekly for up to six cycles). Forty-three patients were recruited of whom 37 were evaluable. Seventy-three per cent were aged >60 years. Over half of the patients received a fludarabine and cyclophosphamide-based regimen as prior CLL treatment. The overall response rate was 46% (complete response 27%, partial response 19%) at six cycles. The median progression-free survival was 6.2 months (95% confidence interval [CI] 4.9-14.0 months) and median OS was 11.4 months (95% CI 6.4-25.6 months). Treatment-naive and TP53-intact patients had improved outcomes. Fifteen episodes of neutropenic fever and 46 non-neutropenic infections were observed. There were no treatment related deaths. Seven patients received platinum-containing salvage at progression, with only one patient obtaining an adequate response to proceed to allogeneic transplantation. CHOP-O with ofatumumab maintenance provides minimal benefit beyond CHOP plus rutuximab. Standard immunochemotherapy for RS remains wholly inadequate for unselected RS. Multinational trials incorporating novel agents are urgently needed. PMID- 27378087 TI - 50 years of amino acid hydrophobicity scales: revisiting the capacity for peptide classification. AB - BACKGROUND: Physicochemical properties are frequently analyzed to characterize protein-sequences of known and unknown function. Especially the hydrophobicity of amino acids is often used for structural prediction or for the detection of membrane associated or embedded beta-sheets and alpha-helices. For this purpose many scales classifying amino acids according to their physicochemical properties have been defined over the past decades. In parallel, several hydrophobicity parameters have been defined for calculation of peptide properties. We analyzed the performance of separating sequence pools using 98 hydrophobicity scales and five different hydrophobicity parameters, namely the overall hydrophobicity, the hydrophobic moment for detection of the alpha-helical and beta-sheet membrane segments, the alternating hydrophobicity and the exact beta-strand score. RESULTS: Most of the scales are capable of discriminating between transmembrane alpha-helices and transmembrane beta-sheets, but assignment of peptides to pools of soluble peptides of different secondary structures is not achieved at the same quality. The separation capacity as measure of the discrimination between different structural elements is best by using the five different hydrophobicity parameters, but addition of the alternating hydrophobicity does not provide a large benefit. An in silico evolutionary approach shows that scales have limitation in separation capacity with a maximal threshold of 0.6 in general. We observed that scales derived from the evolutionary approach performed best in separating the different peptide pools when values for arginine and tyrosine were largely distinct from the value of glutamate. Finally, the separation of secondary structure pools via hydrophobicity can be supported by specific detectable patterns of four amino acids. CONCLUSION: It could be assumed that the quality of separation capacity of a certain scale depends on the spacing of the hydrophobicity value of certain amino acids. Irrespective of the wealth of hydrophobicity scales a scale separating all different kinds of secondary structures or between soluble and transmembrane peptides does not exist reflecting that properties other than hydrophobicity affect secondary structure formation as well. Nevertheless, application of hydrophobicity scales allows distinguishing between peptides with transmembrane alpha-helices and beta-sheets. Furthermore, the overall separation capacity score of 0.6 using different hydrophobicity parameters could be assisted by pattern search on the protein sequence level for specific peptides with a length of four amino acids. PMID- 27378089 TI - Glycosaminoglycan and proteoglycan in skin aging. AB - Glycosaminoglycans (GAGs) and proteoglycans (PGs) are abundant structural components of the extracellular matrix in addition to collagen fibers. Hyaluronic acid (HA), one of GAGs, forms proteoglycan aggregates, which are large complexes of HA and HA-binding PGs. Their crosslinking to other matrix proteins such as the collagen network results in the formation of supermolecular structures and functions to increase tissue stiffness. Skin aging can be classified as intrinsic aging and photoaging based on the phenotypes and putative mechanism. While intrinsic aging is characterized by a thinned epidermis and fine wrinkles caused by advancing age, photoaging is characterized by deep wrinkles, skin laxity, telangiectasias, and appearance of lentigines and is mainly caused by chronic sun exposure. The major molecular mechanism governing skin aging processes has been attributed to the loss of mature collagen and increased matrix metalloproteinase expression. However, various strategies focusing on collagen turnover remain unsatisfactory for the reversal or prevention of skin aging. Although the expression of GAGs and PGs in the skin and their regulatory mechanisms are not fully understood, we and others have elucidated various changes in GAGs and PGs in aged skin, suggesting that these molecules are important contributors to skin aging. In this review, we focus on skin-abundant GAGs and PGs and their changes in human skin during the skin aging process. PMID- 27378088 TI - Integrated Charge Transfer in Organic Ferroelectrics for Flexible Multisensing Materials. AB - The ultimate or end point of functional materials development is the realization of strong coupling between all energy regimes (optical, electronic, magnetic, and elastic), enabling the same material to be utilized for multifunctionalities. However, the integration of multifunctionalities in soft materials with the existence of various coupling is still in its early stage. Here, the coupling between ferroelectricity and charge transfer by combining bis(ethylenedithio)tetrathiafulvalene-C60 charge-transfer crystals with ferroelectric polyvinylidene fluoride polymer matrix is reported, which enables external stimuli-controlled polarization, optoelectronic and magnetic field sensing properties. Such flexible composite films also display a superior strain dependent capacitance and resistance change with a giant piezoresistance coefficient of 7.89 * 10(-6) Pa(-1) . This mutual coupled material with the realization of enhanced couplings across these energy domains opens up the potential for multisensing applications. PMID- 27378091 TI - Jerry Schnoor: The Impact on Others. PMID- 27378090 TI - Comet assay: an essential tool in toxicological research. AB - The comet assay is a versatile, reliable, cost-efficient, and fast technique for detecting DNA damage and repair in any tissue. It is useable in almost any cell type and applicable to both eukaryotic and prokaryotic organisms. Instead of highlighting one of the numerous specific aspects of the comet assay, the present review aims at giving an overview about the evolution of this widely applicable method from the first description by Ostling and Johanson to the OECD Guideline 489 for the in vivo mammalian comet assay. In addition, methodical aspects and the influence of critical steps of the assay as well as the evaluation of results and improvements of the method are reviewed. Methodical aspects regarding oxidative DNA damage and repair are also addressed. An overview about the most recent works and relevant cutting-edge reviews based on the comet assay with special regard to, e.g., clinical applications, nanoparticles or environmental risk assessment concludes this review. Taken together, the presented overview raises expectations to further decades of successful applications and enhancements of this excellent method. PMID- 27378092 TI - A Journey with Jerry. PMID- 27378093 TI - An American in Zurich: Jerry Schnoor as an Ambassador for U.S. Environmental Science and Engineering. PMID- 27378096 TI - Asymmetric pulsation of rat carotid artery bifurcation in three-dimension observed by ultrasound imaging. AB - The arterial structure cyclically fluctuates in three-dimensions (3-D) caused by pulsatile blood flow. The evaluation of arterial wall motion and hemodynamics contributes to early diagnosis of carotid atherosclerosis. Ultrasound is one of the most appropriate imaging modalities to evaluate arterial wall motion in real time. Although many previous studies have discussed the mechanical properties of the carotid artery bifurcation (CAB) from the two-dimensional (2-D) view, the spatio-temporal variation of carotid artery geometry in 3-D has not yet been investigated in detail. In this study, the 3-D data set of CAB from rats was acquired using a high spatio-temporal resolution ultrasound imaging system with a 40 MHz probe using mechanical sector scanning. A total of 31 slices of cross section images were stored and a spoke scan algorithm was implemented to radially scan the lumen area in polar coordinates based on a pre-tracked seed point. The boundary of the arterial lumen was segmented using intensity-threshold-based boundary detection and fitted by polynomial regression. Two operators, who were trained with the same protocol to minimize inter- and intra-operator variability, manually segmented the lumen boundary on systolic and diastolic phase from the gray-scale images. Finally, the 3-D lumen geometries of CAB during one cardiac cycle were constructed based on the segmented lumen boundaries. From this constructed 3-D geometry, we observed that the CAB geometry favorably expanded to the anterior/posterior direction, parallel to the sagittal plane; and the manually segmented geometry also confirmed the asymmetrical change in bifurcation geometry. This is the first study on visualization and quantification on the asymmetrical variation of the CAB geometry of a rat in 3-D during a whole cardiac cycle. This finding may be useful in understanding hemodynamic etiology of various cardiovascular diseases such as arterial stenosis and its complications, and also provides reference information for numerical simulation studies on arterial wall motion. PMID- 27378094 TI - Integrated management of childhood illness (IMCI) strategy for children under five. AB - BACKGROUND: More than 7.5 million children younger than age five living in low- and middle-income countries die every year. The World Health Organization (WHO) developed the integrated management of childhood illness (IMCI) strategy to reduce mortality and morbidity and to improve quality of care by improving the delivery of a variety of curative and preventive medical and behavioral interventions at health facilities, at home, and in the community. OBJECTIVES: To evaluate the effects of programs that implement the IMCI strategy in terms of death, nutritional status, quality of care, coverage with IMCI deliverables, and satisfaction of beneficiaries. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register; MEDLINE; EMBASE, Ovid; the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EbscoHost; the Latin American Caribbean Health Sciences Literature (LILACS), Virtual Health Library (VHL); the WHO Library & Information Networks for Knowledge Database (WHOLIS); the Science Citation Index and Social Sciences Citation Index, Institute for Scientific Information (ISI) Web of Science; Population Information Online (POPLINE); the WHO International Clinical Trials Registry Platform (WHO ICTRP); and the Global Health, Ovid and Health Management, ProQuest database. We performed searches until 30 June 2015 and supplemented these by searching revised bibliographies and by contacting experts to identify ongoing and unpublished studies. SELECTION CRITERIA: We sought to include randomised controlled trials (RCTs) and controlled before-after (CBA) studies with at least two intervention and two control sites evaluating the generic IMCI strategy or its adaptation in children younger than age five, and including at minimum efforts to improve health care worker skills for case management. We excluded studies in which IMCI was accompanied by other interventions including conditional cash transfers, food supplementation, and employment. The comparison group received usual health services without provision of IMCI. DATA COLLECTION AND ANALYSIS: Two review authors independently screened searches, selected trials, and extracted, analysed and tabulated data. We used inverse variance for cluster trials and an intracluster co-efficient of 0.01 when adjustment had not been made in the primary study. We used the GRADE (Grades of Recommendation, Assessment, Development and Evaluation Working Group) approach to assess the certainty of evidence. MAIN RESULTS: Two cluster-randomised trials (India and Bangladesh) and two controlled before-after studies (Tanzania and India) met our inclusion criteria. Strategies included training of health care staff, management strengthening of health care systems (all four studies), and home visiting (two studies). The two studies from India included care packages targeting the neonatal period.One trial in Bangladesh estimated that child mortality may be 13% lower with IMCI, but the confidence interval (CI) included no effect (risk ratio (RR) 0.87, 95% CI 0.68 to 1.10; 5090 participants; low certainty evidence). One CBA study in Tanzania gave almost identical estimates (RR 0.87, 95% CI 0.72 to 1.05; 1932 participants).One trial in India examined infant and neonatal mortality by implementing the integrated management of neonatal and childhood illness (IMNCI) strategy including post-natal home visits. Neonatal and infant mortality may be lower in the IMNCI group compared with the control group (infant mortality hazard ratio (HR) 0.85, 95% CI 0.77 to 0.94; neonatal mortality HR 0.91, 95% CI 0.80 to 1.03; one trial, 60,480 participants; low-certainty evidence).We estimated the effect of IMCI on any mortality measured by combining infant and child mortality in the one IMCI and the one IMNCI trial. Mortality may be reduced by IMCI (RR 0.85, 95% CI 0.78 to 0.93; two trials, 65,570 participants; low-certainty evidence).Two trials (India, Bangladesh) evaluated nutritional status and noted that there may be little or no effect on stunting (RR 0.94, 95% CI 0.84 to 1.06; 5242 participants, two trials; low certainty evidence) and there is probably little or no effect on wasting (RR 1.04, 95% CI 0.87 to 1.25; two trials, 4288 participants; moderate-certainty evidence).The Tanzania CBA study showed similar results.Investigators measured quality of care by observing prescribing for common illnesses at health facilities (727 observations, two studies; very low-certainty evidence) and by observing prescribing by lay health care workers (1051 observations, three studies; very low-certainty evidence). We could not confirm a consistent effect on prescribing at health facilities or by lay health care workers, as certainty of the evidence was very low.For coverage of IMCI deliverables, we examined vaccine and vitamin A coverage, appropriate care seeking, and exclusive breast feeding. Two trials (India, Bangladesh) estimated vaccine coverage for measles and reported that there is probably little or no effect on measles vaccine coverage (RR 0.92, 95% CI 0.80 to 1.05; two trials, 4895 participants; moderate certainty evidence), with similar effects seen in the Tanzania CBA study. Two studies measured the third dose of diphtheria, pertussis, and tetanus vaccine; and two measured vitamin A coverage, all providing little or no evidence of increased coverage with IMCI.Four studies (2 from India, and 1 each from Tanzania and Bangladesh) reported appropriate care seeking and derived information from careful questioning of mothers about recent illness. Some studies on effects of IMCI may report better care seeking behavior, but others do not report this.All four studies recorded maternal responses on exclusive breast feeding. They provided mixed results and very low-certainty evidence. Therefore, we do not know whether IMCI impacts exclusive breast feeding.No studies reported on the satisfaction of mothers and service users. AUTHORS' CONCLUSIONS: The mix of interventions examined in research studies evaluating the IMCI strategy varies, and some studies include specific inputs to improve neonatal health. Most studies were conducted in South Asia. Implementing the integrated management of childhood illness strategy may reduce child mortality, and packages that include interventions for the neonatal period may reduce infant mortality. IMCI may have little or no effect on nutritional status and probably has little or no effect on vaccine coverage. Maternal care seeking behavior may be more appropriate with IMCI, but study results have been mixed, providing evidence of very low certainty about whether IMCI has effects on adherence to exclusive breast feeding. PMID- 27378095 TI - Reproducibility of coronary atherosclerotic plaque characteristics in populations with low, intermediate, and high prevalence of coronary artery disease by multidetector computer tomography: a guide to reliable visual coronary plaque assessments. AB - To evaluate the interobserver agreement of visual coronary plaque characteristics by 320-slice multidetector computed tomography (MDCT) in three populations with low, intermediate and high CAD prevalence and to identify determinants for the reproducible assessment of these plaque characteristics. 150 patients, 50 asymptomatic subjects from the general population (low CAD prevalence), 50 symptomatic non-acute coronary syndrome (non-ACS) patients (intermediate CAD prevalence), and 50 ACS patients (high CAD prevalence), matched according to age and gender, were retrospectively enrolled. All coronary segments were evaluated for overall image quality, evaluability, presence of CAD, coronary stenosis, plaque composition, plaque focality, and spotty calcification by four readers. Interobserver agreement was assessed using Fleiss' Kappa (kappa) and intra-class correlation (ICC). Widely used clinical parameters (overall scan quality, presence of CAD, and determination of coronary stenosis) showed good agreement among the four readers, (ICC = 0.66, kappa = 0.73, ICC = 0.74, respectively). When accounting for heart rate, body mass index, plaque location, and coronary stenosis above/below 50 %, interobserver agreement for plaque composition, presence of CAD, and coronary stenosis improved to either good or excellent, (kappa = 0.61, kappa = 0.81, ICC = 0.78, respectively). Spotty calcification was the least reproducible parameter investigated (kappa = 0.33). Across subpopulations, reproducibility of coronary plaque characteristics generally decreased with increasing CAD prevalence except for plaque composition, (limits of agreement: +/-2.03, +/-1.96, +/-1.79 for low, intermediate and high CAD prevalence, respectively). 320-slice MDCT can be used to assess coronary plaque characteristics, except for spotty calcification. Reproducibility estimates are influenced by heart rate, body size, plaque location, and degree of luminal stenosis. PMID- 27378097 TI - Density-dependent effects of larval dispersal mediated by host plant quality on populations of an invasive insect. AB - The success of invasive species is often thought to be due to release from natural enemies. This hypothesis assumes that species are regulated by top-down forces in their native range and are likely to be regulated by bottom-up forces in the invasive range. Neither of these assumptions has been consistently supported with insects, a group which includes many destructive invasive species. Winter moth (Operophtera brumata) is an invasive defoliator in North America that appears to be regulated by larval mortality. To assess whether regulation was caused by top-down or bottom-up forces, we sought to identify the main causes of larval mortality. We used observational and manipulative field and laboratory studies to demonstrate that larval mortality due to predation, parasitism, and disease were minimal. We measured the response of larval dispersal in the field to multiple aspects of foliar quality, including total phenolics, pH 10 oxidized phenolics, trichome density, total nitrogen, total carbon, and carbon-nitrogen ratio. Tree-level declines in density were driven by density-dependent dispersal of early instars. Late instar larvae dispersed at increased rates from previously damaged as compared to undamaged foliage, and in 2015 field larval dispersal rates were related to proportion of oxidative phenolics. We conclude that larval dispersal is the dominant source of density-dependent larval mortality, may be mediated by induced changes in foliar quality, and likely regulates population densities in New England. These findings suggest that winter moth population densities in New England are regulated by bottom-up forces, aligning with the natural enemy release hypothesis. PMID- 27378099 TI - Issues in designing a randomized clinical trial for chronic prostatitis/chronic pelvic pain syndrome: Comment on Wang et al. Randomized controlled trial of levofloxacin, terazosin, and combination therapy in patients with category III chronic prostatitis/chronic pelvic pain syndrome. Int Urol Nephrol. 2016;48:13 18. PMID- 27378098 TI - Root respiratory costs of ion uptake, root growth, and root maintenance in wetland plants: efficiency and strategy of O2 use for adaptation to hypoxia. AB - Oxygen use in roots is an important aspect of wetland plant ecophysiology, and it depends on the respiratory costs of three major processes: ion uptake, root growth, and root maintenance. However, O2 allocation in wetland plants has received little attention. This study aimed to determine the O2 allocation and specific respiratory cost of each process under hypoxic conditions, to better understand the strategy and efficiency of O2 use in wetland plants. The root respiration rate, nitrogen uptake, and root growth in three Carex species with different growth rates were examined under hypoxic conditions using different N sources, and the respiratory costs of ion uptake, root growth, and root maintenance were statistically estimated. All species exhibited low specific costs and low ratios of O2 allocation for root growth (2.0 +/- 0.4 mmol O2 g(-1) and 15.2 +/- 2.7 %, respectively). The specific cost of ion uptake was 20-30 % lower in fast-growing species than in slow-growing species. As plant growth rate increased, the O2 allocation ratio for ion uptake increased, and that for root maintenance decreased. The cost was higher when NO3 (-) was fed, than when NH4 (+) was fed, although the pattern of O2 allocation ratios for three processes was similar for NO3 (-) and NH4 (+). Our results indicate that wetland plants primarily employ an O2 use strategy of minimising the respiratory costs of root growth, and fast-growing plants specifically use O2 to maximise ion uptake. These findings provide new insights into ecophysiological behaviours of roots in adaptation to hypoxia. PMID- 27378100 TI - Self-assembly behaviours of primitive and modern lipid membrane solutions: a coarse-grained molecular simulation study. AB - Researchers have studied the origin of life and the process of evolution on early Earth for decades. However, we lack a comprehensive understanding of biogenesis, because there are many stages in the formation and growth of the first cell. We investigate the self-replication processes of coacervate protocells using computer simulations of single-chain lipid and phospholipid aqueous mixtures. Based on a morphological phase diagram, we develop a model of prebiotic self replication driven by only environmental factors (i.e. temperature and lipid concentrations) without any external force. Moreover, we investigate high concentration structures during the process of self-replication. These structures have an advantage in fusion and repair of cell membranes. Therefore, lipid hot spots may have existed in primordial soup. PMID- 27378101 TI - Realization of tristability in a multiplicatively coupled dual-loop genetic network. AB - Multistability is a crucial recurring theme in cell signaling. Multistability is attributed to the presence of positive feedback loops, but the general condition and essential mechanism for realizing multistability remain unclear. Here, we build a generic circuit model comprising two transcription factors and a microRNA, representing a kind of core architecture in gene regulatory networks. The circuit can be decomposed into two positive feedback loops (PFLs) or one PFL and one negative feedback loop (NFL), which are multiplicatively coupled. Bifurcation analyses of the model reveal that the circuit can achieve tristability through four kinds of bifurcation scenarios when parameter values are varied in a wide range. We formulate the general requirement for tristability in terms of logarithmic gain of the circuit. The parameter ranges for tristability and possible transition routes among steady states are determined by the combination of gain features of individual feedback loops. Coupling two PFLs with bistability or one NFL with a bistable PFL is most likely to generate tristability, but the underlying mechanisms are largely different. We also interpret published results and make testable predictions. This work sheds new light on interlinking feedback loops to realize tristability. The proposed theoretical framework can be of wide applicability. PMID- 27378102 TI - A prognostic model for resectable soft tissue and cutaneous angiosarcoma. AB - BACKGROUND: Angiosarcoma is an aggressive tumor rising in incidence from use of therapeutic radiation. Because of its relative rarity, prognostic factors have not been clearly delineated. METHODS: Patients who underwent resection of localized angiosarcoma from 2002 to 2012 were identified using the National Cancer Data Base. Factors associated with poor overall survival (OS) were identified using Cox proportional hazards modeling and internally validated with bootstrap resampling. These were used to construct a risk model to identify low-, intermediate-, or high-risk groups. RESULTS: Median OS among 821 patients undergoing resection was 3.4 years. On multivariable analysis of factors known preoperatively, those associated with worse OS included: age >70 years (HR 2.02, P < 0.0001), black race (HR 1.92, P < 0.0001), head and neck primary (HR 1.44, P = 0.003), grade 3 tumor (HR 1.53, P = 0.013), size 3-7 cm (HR 1.64, P < 0.0001), size >7 cm (HR 2.37, P < 0.0001). After including postoperative variables, positive resection margins were associated with worse OS (microscopic, HR 1.59, P = 0.002; macroscopic, HR 3.38, P = 0.008). Stratification by risk group was superior to AJCC stage in discriminating OS. CONCLUSIONS: In the largest study to date of patients with angiosarcoma, risk factors for poor OS were identified to create a clinically useful risk model that can prognosticate patients with localized disease following surgical resection. J. Surg. Oncol. 2016;114:557-563. (c) 2016 Wiley Periodicals, Inc. PMID- 27378103 TI - The association of timing of retirement with cognitive performance in old age: the role of leisure activities after retirement. AB - BACKGROUND: The role of timing of retirement on cognitive functioning in old age is inconclusive so far. Therefore, the present study set out to investigate the association of timing of retirement with cognitive performance and its interplay with key correlates of cognitive reserve in a large sample of older adults. METHODS: Two thousand two hundred and sixty three older adults served as sample for the present study. Different psychometric tests (Trail Making Test part A (TMT A), Trail Making Test part B (TMT B), Mill Hill) were administered. In addition, individuals were interviewed on their retirement, occupation, educational attainment, and regarding 18 leisure activities that have been carried out after retirement. RESULTS: Earlier retirement (compared to retirement at legal age) was significantly associated with better performance in the TMT A, the TMT B, and the Mill Hill vocabulary test. Moderation analyses showed that in individuals with a moderate number of leisure activities in old age, earlier retirement was related to better cognitive performance, but not in those with a relatively large number of leisure activities. Hierarchical regression analyses revealed that entering leisure activities as additional predictor significantly increased explained variance in the cognitive measures over and above all other investigated markers of cognitive reserve (i.e. occupation and education). CONCLUSIONS: Present data further corroborate the view that leisure activities even in old age may lead to further enrichment effects and thereby may be related to better cognitive functioning. The role of engaging in activities in the context of major life events such as retirement is discussed. PMID- 27378104 TI - Calixarene Assisted Rapid Synthesis of Silver-Graphene Nanocomposites with Enhanced Antibacterial Activity. AB - Demonstrated herein is a single rapid approach employed for synthesis of Ag graphene nanocomposites, with excellent antibacterial properties and low cytotoxicity, by utilizing a continuous hydrothermal flow synthesis (CHFS) process in combination with p-hexasulfonic acid calix[6]arene (SCX6) as an effective particle stabilizer. The nanocomposites showed high activity against E. coli (Gram-negative) and S. aureus (Gram-positive) bacteria. The materials were characterized using a range of techniques including transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, UV vis spectrophotometry, FT-IR, and X-ray powder diffraction (XRD). This rapid, single step synthetic approach not only provides a facile means of enabling and controlling graphene reduction (under alkaline conditions) but also offers an optimal route for homogeneously producing and depositing highly crystalline Ag nanostructures into reduced graphene oxide substrate. PMID- 27378106 TI - Phosphine-Catalyzed [2 + 4] Annulation of Allenoates with Thiazolone-Derived Alkenes: Synthesis of Functionalized 6,7-Dihydro-5H-pyrano[2,3-d]thiazoles. AB - Phosphine-catalyzed [2 + 4] annulation of allenoates with thiazolone-derived alkenes has been achieved under mild conditions, giving biologically important 6,7-dihydro-5H-pyrano[2,3-d]thiazole derivatives in high to excellent yields. With the use of Kwon's phosphine as the chiral catalyst, optically active products were obtained in good yields with excellent enantioselectivities. PMID- 27378105 TI - Nature-Inspired One-Step Green Procedure for Enhancing the Antibacterial and Antioxidant Behavior of a Chitin Film: Controlled Interfacial Assembly of Tannic Acid onto a Chitin Film. AB - The final goal of this study was to develop antimicrobial food-contact materials based on a natural phenolic compound (tannic acid) and chitin, which is the second most abundant polysaccharide on earth, using an interfacial assembly approach. Chitin film has poor antibacterial and antioxidant ability, which limits its application in industrial fields such as active packaging. Therefore, in this study, a novel one-step green procedure was applied to introduce antibacterial and antioxidant properties into a chitin film simultaneously by incorporation of tannic acid into the chitin film through interfacial assembly. The antibacterial and antioxidant behavior of chitin film has been greatly enhanced. Hydrogen bonds and hydrophobic interaction were found to be the main driving forces for interfacial assembly. Therefore, controlled interfacial assembly of tannic acid onto a chitin film demonstrated a good way to develop functional materials that can be potentially applied in industry. PMID- 27378107 TI - Li BO-Pioneer of Ecology in China. PMID- 27378120 TI - Absence of Evidence or Evidence of Absence? Commentary: Captured by the pain: Pain steady-state evoked potentials are not modulated by selective spatial attention. PMID- 27378121 TI - Radiofrequency ablation of varicose veins improves venous clinical severity score despite failure of complete closure of the saphenous vein after 1 year. AB - BACKGROUND AND OBJECTIVES: Endovenous treatment is increasingly supplanting open surgery for the treatment of varicose veins. Among emerging endovenous techniques, radiofrequency ablation (RFA) with a ClosureFast catheter is popular in Korea. The objective of this study was to evaluate and compare the efficacy and patient-reported outcomes of RFA of varicose veins. METHODS: This is a retrospective study of a prospectively registered database of patients who underwent RFA for varicose veins from 2012 to 2013 in St. Mary's Hospital in Seoul. Korea. Efficient ClosureFast RFA catheters (Medtronic, San Jose, CA, USA) were used. The techniques used for RFA of varicose veins were performed according to the manufacturer's recommendations. Duplex scans and venous clinical severity scores (VCSSs) were used to document treatment outcome and patient symptoms before and after the procedures. Treatment outcomes were estimated before the procedure and 3 months, 6 months, and 12 months after the procedure. Outcomes were analyzed by paired t test, chi-square test, or Fisher's exact test as well as by logistical regression. RESULTS: A total of 117 patients were evaluated for 183 consecutive RFA procedures (183 limbs). The initial technical success was 97.3% (178/183). The estimated mean VCSS changed over time from 4.0 +/- 1.67 at preprocedure to 0.6 +/- 1.05, 0.5 +/- 1.02, and 0.6 +/- 1.14 at 3 months, 6 months, and 12 months after the procedure, respectively. The improved VCSS was maintained 1 year after the procedure (p < 0.001). Recanalization of the saphenous vein was detected in 20 limbs at the 1-year follow up. The treatment failure group also exhibited a significant decline in the VCSS between preprocedure and 12 months (4.8 +/- 1.76 vs. 1.8 +/- 2.04, p < 0.001). Specifically, in the treatment failure group, 65% of limbs with episodic recanalization (13/20) were reoccluded or recanalized without venous reflux at the 1-year follow up. CONCLUSION: In this study, RFA of varicose veins had an initial success rate of 97.7% and a significantly improved patient VCSS at 1 year. Patients with episodic recanalization of the saphenous vein also exhibited an improved VCSS with favorable duplex findings at 1 year. PMID- 27378122 TI - Longitudinal Trajectories of Television Watching Across Childhood and Adolescence Predict Bone Mass at Age 20 Years in the Raine Study. AB - Sedentary behaviors such as watching television (TV) are associated with increased risk of cardiometabolic disease. The effects of TV watching during key developmental stages on skeletal health are uncertain. Hours of TV watching/week were recorded by parental or self-report at 5, 8, 10, 14, 17, and 20 years of age in 1181 members (48% female) of a pregnancy cohort (the Raine Study). Participants were classified into one of three TV-watching trajectories (using latent class analysis): low (consistently <14 h/week; 20.3%), high (consistently >=14 h/week; 44.4%), or increasing (increased from <14 to >=14 h/week during adolescence; 35.3%). General linear models tested associations between TV trajectory and bone mineral content (BMC) measured at age 20 years using dual energy X-ray absorptiometry. After adjustment for height, body mass, physical activity, calcium intake, serum 25-hydroxyvitamin D levels, alcohol, and smoking (all at age 20 years), males in the low TV-watching trajectory had greater BMC for whole body (mean +/- SEM, 3338 +/- 59 g versus 3111 +/- 31 g), legs (612 +/- 12 g versus 569 +/- 6 g), and arms (234 +/- 5 g versus 214 +/- 3 g) than those in the high TV-watching trajectory. Differences between low and high TV-watching trajectories were similar for females. BMC in the increasing TV-watching trajectory also differed for both sexes, for example males in the increasing TV watching trajectory had greater whole-body BMC (3252 +/- 38 g) than males in the high TV-watching trajectory (3111 +/- 31 g) but less arm BMC (218 +/- 3 g) than those in the low TV-watching trajectory (234 +/- 5 g). In this community-based cohort, consistently high TV watching during childhood and adolescence independently predicted reduced peak bone mass at age 20 years. Because attainment of optimal peak bone mass is protective against osteoporosis in later life, reducing sedentary time in children may have long-term skeletal benefits. (c) 2016 American Society for Bone and Mineral Research. PMID- 27378123 TI - Are rural and remote patients, families and caregivers needs in life-limiting illness different from those of urban dwellers? A narrative synthesis of the evidence. AB - This review aimed to assess the evidence to answer the question whether palliative end-of-life care needs of patients and caregivers in rural and remote communities differs from those of urban dwellers. Peer-reviewed studies from 1996 to the present dealing with the experience of rural and remote patients and caregivers at the end-of-life compared with that of urban people were extracted for narrative synthesis. The eight studies included showed that palliative needs of rural and remote residents are related to context. Diagnosis and treatment are less well managed in rural areas. Rural differences include: people are more accepting of death and less likely to intervene to delay death; caregivers tend to be younger and include friends as well as family and local support networks are important. Rural and remote end-of-life needs are shaped by reduced access and availability of services which has a negative influence on outcomes. This is counterbalanced by an acceptance of death and local support networks. Well designed longitudinal studies with samples comprised of rural and urban residents for comparison are required to monitor how end-of-life need might change with the approach of death. Clinicians, health services and policy makers need a better understanding of rural attitudes and of how rural community networks mobilise to support end-of-life care in their rural and remote communities. PMID- 27378124 TI - Outcomes in infants listed for liver transplantation: A retrospective cohort study using the United Network for Organ Sharing database. AB - LT in neonates and young infants can be challenging due to a variety of factors. To describe the waitlist mortality rates and outcomes of patients listed and transplanted as infants identified from the UNOS database. Infants listed for LT between January 1985 and September 2010 were identified from the UNOS database. Mortality on the waitlist as well as outcomes post-LT was compared between infants aged <=60 days (Group 1), 61-179 days (Group 2), and 180-364 days (Group 3). Of 6763 infants listed for LT (Group 1 n = 496, Group 2 n = 2404, Group 3 n = 3863), mean age at listing was 196 +/- 87 days (Group 1, 29 +/- 16 days; Group 2, 132 +/- 32 days; Group 3, 257 +/- 52 days). Waitlist mortality was highest in Group 1 (Group 1 vs. 3 HR 3.01, 95% CI 2.19-4.15, Group 2 vs. Group 3 HR 0.82, 95% CI 0.66-1.03). One- and five-yr graft survival was 59.6% and 42% (Group 1), 66% and 45% (Group 2), and 66.8% and 41% (Group 3) (one-yr survival p = 0.20; five-yr survival p = 0.19). Infants listed for LT at age <=60 days had greater waitlist mortality risk than older infants. Infants undergoing LT at age <=60 days had similar rates of patient and graft survival to older infants. PMID- 27378125 TI - Genetic association of stomatal traits and yield in wheat grown in low rainfall environments. AB - BACKGROUND: In wheat, grain filling is closely related to flag leaf characteristics and function. Stomata are specialized leaf epidermal cells which regulate photosynthetic CO2 uptake and water loss by transpiration. Understanding the mechanisms controlling stomatal size, and their opening under drought, is critical to reduce plant water loss and maintain a high photosynthetic rate which ultimately leads to elevated yield. We applied a leaf imprinting method for rapid and non-destructive phenotyping to explore genetic variation and identify quantitative traits loci (QTL) for stomatal traits in wheat grown under greenhouse and field conditions. RESULTS: The genetics of stomatal traits on the adaxial surface of the flag leaf was investigated using 146 double haploid lines derived from a cross between two Australian lines of Triticum aestivum, RAC875 and Kukri. The drought tolerant line RAC875 showed numerous small stomata in contrast to Kukri. Significant differences between the lines were observed for stomatal densitity and size related traits. A negative correlation was found between stomatal size and density, reflecting a compensatory relationship between these traits to maintain total pore area per unit leaf surface area. QTL were identified for stomatal traits on chromosomes 1A, 1B, 2B, and 7A under field and controlled conditions. Most importantly some of these loci overlap with QTL on chromosome 7A that control kernel number per spike, normalized difference vegetation index, harvest index and yield in the same population. CONCLUSIONS: In this first study to decifer genetic relationships between wheat stomatal traits and yield in response to water deficit, no significant correlations were observed among yield and stomatal traits under field conditions. However we found some overlaps between QTL for stomatal traits and yield across environments. This suggested that stomatal traits could be an underlying mechanism increasing yield at specific loci and used as a proxy to track a target QTL in recombinant lines. This finding is a step-forward in understanding the function of these loci and identifying candidate genes to accelerate positional cloning of yield QTL in wheat under drought. PMID- 27378126 TI - Pathophysiology and preventive strategies of anthracycline-induced cardiotoxicity. AB - Cardiotoxicity is a well-known complication following treatment with anthracyclines. However, they are still widely used in chemotherapy for breast cancer, lymphoma, leukemia, and sarcoma, among others. Patient clinical characteristics, such as age, sex, comorbidities, anthracycline dose and infusion schedule, and the combined anti-cancer agents used, are diverse among cancer types. It is difficult to recommend guidelines for the prevention or management of anthracycline-induced cardiotoxicity applicable to all cancer types. Therefore, anthracycline-induced cardiotoxicity remains a major limitation in the proper management of cancer patients treated with an anthracycline-combined regimen. Efforts have been extensive to determine the mechanism and treatment of anthracycline-induced cardiotoxicity. Because cardiotoxicity causes irreversible damage to the myocardium, prevention is a more effective approach than treatment of cardiotoxicity after symptomatic or asymptomatic cardiac dysfunction develops. This article will review the pathophysiological mechanisms of anthracycline induced cardiotoxicity and strategies for protecting the myocardium from anthracycline. PMID- 27378127 TI - High prevalence of chronic obstructive pulmonary disease in Korea. PMID- 27378129 TI - Long-term use of calcium channel blocking drugs and breast cancer risk in a prospective cohort of US and Puerto Rican women. AB - BACKGROUND: In a recent case-control study, long-term use of calcium channel blocking drugs was associated with a greater-than-twofold increased breast cancer risk. If prospectively collected data confirm that calcium channel blocker use increases breast cancer risk, this would have major implications for hypertension treatment. The objective of this study was to determine whether women using calcium channel blockers for 10 years or more were at increased risk of developing breast cancer compared with women not using calcium channel blockers. METHODS: The Sister Study is a prospective volunteer cohort study of women from the USA and Puerto Rico designed to evaluate environmental and genetic risk factors for breast cancer. Beginning in 2003, women between the ages of 35 and 74 were recruited. They were eligible to participate if they had a sister with breast cancer but had not been diagnosed with breast cancer themselves. In total, 50,884 women enrolled in the cohort between 2003 and 2009; 50,757 women with relevant baseline data and available follow-up data are included in this study. The exposure of interest is current use of calcium channel blocking drugs and the reported duration of use at entry into the cohort. Secondary exposures of interest were the duration and frequency of use for all other subclasses of antihypertensive drugs. Our main outcome is a self-reported diagnosis of breast cancer during the study follow-up period. With patient permission, self-reported diagnoses were confirmed using medical records. RESULTS: Results showed 15,817 participants were currently using an antihypertensive drug, and 3316 women were currently using a calcium channel blocker at study baseline; 1965 women reported a breast cancer diagnosis during study follow-up. Using Cox proportional hazards modeling, we found no increased risk of breast cancer among women who had been using calcium channel blockers for 10 years or more compared with never users of calcium channel blockers (HR 0.88, 95 % CI 0.58-1.33). CONCLUSIONS: We saw no evidence of increased risk of breast cancer from 10 years or more of current calcium channel blocker use. Our results do not support avoiding calcium channel blocking drugs in order to reduce breast cancer risk. PMID- 27378130 TI - Common Mechanism of Cross-Resistance Development in Pathogenic Bacteria Bacillus cereus Against Alamethicin and Pediocin Involves Alteration in Lipid Composition. AB - To understand the mechanism of development of cross-resistance in food pathogen Bacillus cereus against an antimicrobial peptide pediocin and antibiotic alamethicin, the present study was designed. Pediococcus pentosaceus was taken as a source of pediocin, and it was purified by ammonium sulphate precipitation followed by cation exchange chromatography with 14.01-fold purity and 14.4 % recovery. B. cereus strains alamethicin-resistant strains (IC50 3.23 ug/ml) were selected from sensitive population with IC50 2.37 ug/ml. The development of resistance in B. cereus against alamethicin was associated with decrease in alamethicin-membrane interaction observed by in vitro assay. Resistant strain of B. cereus was found to harbour one additional general lipid as compared to sensitive strain, one amino group lacking phospholipid and one amino group containing phospholipid (ACP). In addition, ACP content was increased in resistant mutant (29.7 %) as compared to sensitive strain (14.56 %). The alamethicin-resistant mutant B. cereus also showed increased IC50 (58.8 AU/ml) for pediocin as compared to sensitive strain (IC50 47.8 AU/ml). Cross-resistance to pediocin and alamethicin in resistant mutant of B. cereus suggested a common mechanism of resistance. Therefore, this understanding could result in the development of peptide which will be effective against the resistant strains that share same mechanism of resistance. PMID- 27378131 TI - Comparative Analysis of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) of Streptococcus thermophilus St-I and its Bacteriophage-Insensitive Mutants (BIM) Derivatives. AB - The CRISPR-Cas (CRISPR together with CRISPR-associated proteins) modules are the adaptive immune system, acting as an adaptive and heritable immune system in bacteria and archaea. CRISPR-based immunity acts by integrating short virus sequences in the cell's CRISPR locus, allowing the cell to remember, recognize, and clear infections. In this study, the homology of CRISPRs sequence in BIMs (bacteriophage-insensitive mutants) of Streptococcus thermophilus St-I were analyzed. Secondary structures of the repeats and the PAMs (protospacer associated motif) of each CRISPR locus were also predicted. Results showed that CRISPR1 has 27 repeat-spacer units, 5 of them had duplicates; CRISPR2 has one repeat-spacer unit; CRISPR3 has 28 repeat-spacer units. Only BIM1 had a new spacer acquisition in CRISPR3, while BIM2 and BIM3 had no new spacers' insertion, thus indicating that while most CRISPR1 were more active than CRISPR3, new spacer acquisition occurred just in CRSPR3 in some situations. These findings will help establish the foundation for the study of CRSPR-Cas systems in lactic acid bacteria. PMID- 27378132 TI - Catalyzing Transdisciplinarity: A Systems Ethnography of Cancer-Obesity Comorbidity and Risk Coincidence. AB - Effectively addressing wicked health problems, that is, those arising from complex multifactorial biological and socio-economic causes, requires transdisciplinary action. However, a significant body of research points toward substantial difficulties in cultivating transdisciplinary collaboration. Accordingly, this article presents the results of a study that adapts Systems Ethnography and Qualitative Modeling (SEQM) in response to wicked health problems. SEQM protocols were designed to catalyze transdisciplinary responses to national defense concerns. We adapted these protocols to address cancer-obesity comorbidity and risk coincidence. In so doing, we conducted participant observations and interviews with a diverse range of health care providers, community health educators, and health advocacy professionals who target either cancer or obesity. We then convened a transdisciplinary conference designed to catalyze a coordinated response. The findings offer productive insights into effective ways of catalyzing transdisciplinarity in addressing wicked health problems action and demonstrate the promise of SEQM for continued use in health care contexts. PMID- 27378134 TI - Chronic Prostate Inflammation is Associated with Severity and Progression of Benign Prostatic Hyperplasia, Lower Urinary Tract Symptoms and Risk of Acute Urinary Retention. AB - PURPOSE: We evaluated associations between histological prostate inflammation, and the development and progression of benign prostatic hyperplasia/lower urinary tract symptoms in men randomized to placebo in the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) study in a 4-year period. MATERIALS AND METHODS: The association of acute and chronic inflammation detected on baseline biopsies and benign prostatic hyperplasia related parameters, including I-PSS (International Prostate Symptom Score) and prostate volume, at multiple time points during 4 years in men randomized to placebo enrolled in the REDUCE prostate cancer prevention study was analyzed with the Student t-test. The association of inflammation with newly developed benign prostatic hyperplasia/lower urinary tract symptoms and benign prostatic hyperplasia progression in patients with existing benign prostatic hyperplasia/lower urinary tract symptoms was analyzed with univariable and multivariable Cox models. RESULTS: Acute and chronic inflammation was seen in baseline negative biopsies of 641 (15.6%) and 3,216 (78.3%) of the 4,109 men in the study. Chronic but not acute inflammation was associated with slightly higher baseline I-PSS (0.6 difference, p = 0.001) and larger prostate volume (3.2 cc difference, p <0.001), a difference noted throughout the study interval. The presence of acute and chronic inflammation was not associated with the incidence of benign prostatic hyperplasia/lower urinary tract symptoms in men without those conditions at baseline or the progression of symptomatic benign prostatic hyperplasia in men with benign prostatic hyperplasia/lower urinary tract symptoms at baseline. However, an association was observed with more severe inflammation. Chronic inflammation at baseline was associated with an increased risk of acute urinary retention (HR 1.6-1.8, p = 0.001). CONCLUSIONS: Our longitudinal evaluation of REDUCE patients randomized to placebo for 4 years confirmed that chronic inflammation is associated with severity and the progression of benign prostatic hyperplasia and benign prostatic hyperplasia/lower urinary tract symptom outcomes. PMID- 27378133 TI - Pursuing Authenticity From Process to Outcome in a Community-Based Participatory Research Study of Intimate Partner Violence and HIV Vulnerability in North Karnataka, India. AB - Community-based participatory research has been seen to hold great promise by researchers aiming to bridge research and action in global health programs and practice. However, there is still much debate around whether achieving authenticity in terms of in-depth collaboration between community and academic partners is possible while pursuing academic expectations for quality. This article describes the community-based methodology for a qualitative study to explore intimate partner violence and HIV/AIDS among women in sex work, or female sex workers, and their male partners in Karnataka, South India. Developed through collaborative processes, the study methodology followed an interpretive approach to qualitative inquiry, with three key components including long-term partnerships, knowledge exchange, and orientation toward action. We then discuss lessons learned on how to pursue authenticity in terms of truly collaborative processes with inherent value that also contribute to, rather than hinder, the instrumental goal of enhancing the quality and relevance of the research outcomes. PMID- 27378135 TI - Sensory Hyperinnervation Distinguishes Bladder Pain Syndrome/Interstitial Cystitis from Overactive Bladder Syndrome. AB - PURPOSE: Pain is the key symptom that distinguishes bladder pain syndrome/interstitial cystitis from overactive bladder syndrome but overlap occurs. To find a discriminating marker for these bladder diseases we examined sensory hyperinnervation and neurotrophin receptor expression in bladder biopsies as well as nerve growth factor levels in urine. MATERIALS AND METHODS: Bladder biopsies from patients with bladder pain syndrome/interstitial cystitis, including 12 with and 19 without Hunner lesions, 13 with overactive bladder syndrome and 12 healthy controls, were analyzed by immunohistochemistry with antibodies to the nerve cell marker PGP9.5 (neuron-specific protein gene product 9.5), p75NTR (p75 neurotrophin receptor), the B-lymphocyte marker CD20 and mast cell tryptase. Urinary nerve growth factor was quantified by enzyme-linked immunosorbent assay. RESULTS: Subepithelial sensory hyperinnervation on PGP9.5 staining had 97% sensitivity and 76% specificity, increased lymphocytic infiltration had 90% sensitivity and 80% specificity, and urothelial defects had 97% sensitivity and 76% specificity to distinguish bladder pain syndrome/interstitial cystitis with and without Hunner lesions from overactive bladder syndrome and healthy controls. Increased sensory innervation was associated with submucosal mast cell localization. Staining of p75NTR in basal urothelial cells was indicative of bladder pain syndrome/interstitial cystitis. Urinary nerve growth factor levels were below the detection level and did not differentiate bladder diseases from healthy controls. CONCLUSIONS: Sensory hyperinnervation and basal urothelial p75NTR staining together with assessment of inflammatory lymphocytes and urothelial integrity allow for the differentiation of bladder pain syndrome/interstitial cystitis and overactive bladder syndrome even in the absence of Hunner lesions. Furthermore, these histopathological criteria enable the identification of early disease stages or oligosymptomatic/asymptomatic cases and may permit timely treatment to prevent disease progress. PMID- 27378137 TI - Corrigendum to "Oxygen-independent FbFP: Fluorescent sentinel and oxygen sensor component in Saccharomyces cerevisiae and Candida albicans" [Fungal Genet. Biol. 92 (2016) 14-25]. PMID- 27378136 TI - Atypical presentation of autoimmune lymphoproliferative syndrome due to CASP10 mutation. AB - Herein we describe the case of a 8-years-old boy with diagnosis of atypical autoimmune lymphoproliferative syndrome (ALPS), carrying heterozygous mutation of CASP10 gene (I406L). He presented with multiple non-invasive infections of the skin, that were associated to chronic non-malignant non-infectious lymphadenopathy, failure to thrive, weakness, arthralgia, relapsing oral aftosis, and expansion of TCRalphabeta(+) CD4(-)/CD8(-) T cells. This observation suggests that cutaneous infections can be observed in ALPS patients carrying CASP10 mutations. PMID- 27378138 TI - Time series modeling of pathogen-specific disease probabilities with subsampled data. AB - Many diseases arise due to exposure to one of multiple possible pathogens. We consider the situation in which disease counts are available over time from a study region, along with a measure of clinical disease severity, for example, mild or severe. In addition, we suppose a subset of the cases are lab tested in order to determine the pathogen responsible for disease. In such a context, we focus interest on modeling the probabilities of disease incidence given pathogen type. The time course of these probabilities is of great interest as is the association with time-varying covariates such as meteorological variables. In this set up, a natural Bayesian approach would be based on imputation of the unsampled pathogen information using Markov Chain Monte Carlo but this is computationally challenging. We describe a practical approach to inference that is easy to implement. We use an empirical Bayes procedure in a first step to estimate summary statistics. We then treat these summary statistics as the observed data and develop a Bayesian generalized additive model. We analyze data on hand, foot, and mouth disease (HFMD) in China in which there are two pathogens of primary interest, enterovirus 71 (EV71) and Coxackie A16 (CA16). We find that both EV71 and CA16 are associated with temperature, relative humidity, and wind speed, with reasonably similar functional forms for both pathogens. The important issue of confounding by time is modeled using a penalized B-spline model with a random effects representation. The level of smoothing is addressed by a careful choice of the prior on the tuning variance. PMID- 27378139 TI - Relationship between high blood pressure and cardiovascular outcomes in elderly frail patients: A systematic review and meta-analysis. AB - Prior studies have suggested that lower blood pressure increases the mortality risk in the elderly. This study examines the relationship between change in blood pressure and overall mortality in frail elderly patients. Medline, PubMed, Cochrane, and Google Scholar databases were searched until April 2, 2015 using search terms: frail/frailty, elderly/aged, blood pressure, hypertension, cardiovascular events, and mortality/prognosis. Two-arm prospective and retrospective studies that investigated BP and the incidence of mortality in frail elderly patients were included. We found that the chance of mortality decreased with increasing systolic blood pressure (SBP) (pooled HR = 0.870, 95% CI = 0.776-0.976, P = 0.018) and diastolic blood pressure (DBP) (pooled HR = 0.837, 95% CI = 0.77-0.911, P < 0.001). Pulse pressure was not associated with mortality risk (pooled HR = 0.949, 95% CI = 0.897-1.004, P < 0.071). In elderly frailty patients, hypertension has a protective effect in lowering risk of overall mortality. Accurate identification of such elderly population is necessary for optimizing health care. PMID- 27378140 TI - Testing a Revised Interpersonal Theory of Depression Using a Laboratory Measure of Excessive Reassurance Seeking. AB - OBJECTIVE: This study tested whether core beliefs with themes of abandonment and rejection moderated the link between trait and behavioral excessive reassurance seeking (ERS) and interpersonal rejection. METHOD: Participants were 118 women with high (n = 43; mean [M]age = 18.58, standard deviation [SD]age = 1.24) and low (n = 75; Mage = 18.58, SDage = 1.24) levels of depression symptoms and their male romantic partners. Couples reported their depression, ERS, abandonment/rejection cognitions, and relationship quality. We also coded women's reassurance-seeking behavior during an audiotaped discussion task. RESULTS: Among women with high levels of depression symptoms and low levels of abandonment/rejection core beliefs, behavioral ERS was associated with lower partner-reported relationship quality. Self-reported ERS was significantly associated with partner relationship quality, but the effect was not moderated by depression or core beliefs. CONCLUSIONS: ERS is a potent predictor of stress and subsequent depression. Our findings underscore the need to better understand factors (e.g., cognitions, partner characteristics) that may determine whether ERS behaviors beget interpersonal stress and rejection. PMID- 27378141 TI - Atrial Remodeling and Atrial Tachyarrhythmias in Arrhythmogenic Right Ventricular Cardiomyopathy. AB - Less is known about atrial remodeling and atrial tachyarrhythmias (ATa) in arrhythmogenic right ventricular cardiomyopathy (ARVC); this cross-sectional study aimed to determine the prevalence, characterization, and predictors of atrial remodeling and ATa in a large series of patients with ARVC. From February 2004 to September 2014, 294 consecutive patients who met the task force criteria for ARVC were enrolled. The prevalence, characterization, and predictors of atrial dilation and ATa were investigated. Right atrium (RA) dilation was identified in 160 patients (54.4%) and left atrium dilation in 66 patients (22.4%). Both RA and left atrium dilation were found in 44 patients (15.0%). Twenty-five patients (8.5%) had atrial fibrillation (AF), whereas 19 patients (6.5%) had atrial flutter (AFL). Of which, 7 patients (2.4%) had both AF and AFL. Multivariate analysis showed that AFL (odds ratio [OR] 10.309; 95% confidence interval [CI] 2.770 to 38.462; p <0.001), hypertension (OR 9.174; 95% CI 2.364 to 35.714; p = 0.001), and RA dilation (OR 6.993; 95% CI 1.623 to 30.303; p = 0.009) were associated with increased risk for AF. AF (OR 10.526; 95% CI 2.786 to 40.000; p = 0.001) increased the risk of AFL. In conclusion, atrial remodeling and ATa were common in patients with ARVC. PMID- 27378143 TI - Comparative Efficacy of Transradial Versus Transfemoral Approach for Coronary Angiography and Percutaneous Coronary Intervention. AB - Transradial artery (TRA) approach is associated with fewer vascular complications and reduced mortality in patients at high risk compared with transfemoral approach (TFA). The objective of our study was to compare the characteristics and outcomes of patients who had coronary angiography by TRA and TFA over the course of hospital implementation of this approach. We included 12,928 patients from Baylor University Medical Center and Baylor Heart and Vascular Hospital, Dallas, Texas, who underwent a coronary angiography from January 2008 to March 2015. To control for selection bias and the learning curve, a nested matched study design was used for patients with percutaneous coronary intervention (PCI) with TRA patients matched with TFA by age (+/-2 years) and calendar year of the procedure in a ratio of 1:3. TRA for PCI increased from nearly 0% in 2008 to 9% in 2014. Including patients from 2011 to 2015 for the analysis, patients with TFA were older (65 +/- 12 vs 64 +/- 11) and had lower mean body mass index (30 +/- 7 vs 33 +/- 9 kg/m(2)) than patients with TRA. Patients with TRA had less bleeding, dialysis, pseudoaneurysm, and access site hematomas than the patients with TRA (0.7% vs 0%; p = 0.02). By a conditional logistic regression, we observed fewer complications, readmissions, and in-hospital deaths among TRA patients than the matched TFA patients. In conclusion, patients undergoing angiography with/without PCI through TRA had fewer complications, readmissions, and a shorter length of hospital stay after procedure versus TFA at our hospital. PMID- 27378142 TI - Puncture Versus Surgical Cutdown Complications of Transfemoral Aortic Valve Implantation (from the Spanish TAVI Registry). AB - Vascular complications in transcatheter aortic valve implantation using transfemoral approach are related to higher mortality. Complete percutaneous approach is currently the preferred technique for vascular access. However, some centers still perform surgical cutdown. Our purpose was to determine complications related to vascular access technique in the population of the Spanish TAVI National Registry. From January 2010 to July 2015, 3,046 patients were included in this Registry. Of them, 2,465 underwent transfemoral approach and were treated with either surgical cutdown and closure (cutdown group, n = 632) or percutaneous approach (puncture group, n = 1,833). Valve Academic Research Consortium-2 definitions were used to assess vascular and bleeding complications. Propensity matching resulted in 615 matched pairs. Overall, 30-day vascular complications were significantly higher in the puncture group (109 [18%] vs 42 [6.9%]; relative risk [RR] 2.60; 95% confidence interval [CI] 1.85 to 3.64, p <0.001) due mostly by minor vascular events (89 [15%] vs 25 [4.1%], RR 3.56, 95% CI 2.32 to 5.47, p <0.001). Bleeding rates were lower in the puncture group (18 [3%] vs 40 [6.6%], RR 0.45, 95% CI 0.26 to 0.78, p = 0.003) mainly driven by major bleeding (9 [1.5%] vs 21 [3.4%], RR 0.43, 95% CI 0.20 to 0.93, p = 0.03). At a mean follow-up of 323 days, complication rates remained significantly different between groups (minor vascular complications 90 [15%] vs 31 [5.1%], hazard ratio 2.99, 95% CI 1.99 to 4.50, p <0.001 and major bleeding 10 [1.6%] vs 21 [3.4%], hazard ratio 0.47, 95% CI 0.22 to 1.0, p = 0.04, puncture versus cutdown group, respectively). In conclusion, percutaneous approach yielded higher rates of minor vascular complications but lower rates of major bleeding compared with the surgical cutdown, both at 30-day and at mid-term follow-up in our population. PMID- 27378145 TI - Pioneering In Situ Recrystallization during Bead Milling: A Top-down Approach to Prepare Zeolite A Nanocrystals. AB - Top-down approach has been viewed as an efficient and straightforward method to prepare nanosized zeolites. Yet, the mechanical breaking of zeolite causes amorphization, which usually requires a post-milling recrystallization to obtain fully crystalline nanoparticles. Herein we present a facile methodology to prepare zeolite nanocrystals, where milling and recrystallization can be performed in situ. A milling apparatus specially designed to work under conditions of high alkalinity and temperature enables the in situ recrystallization during milling. Taking zeolite A as an example, we demonstrate its size reduction from ~3 MUm to 66 nm in 30 min, which is quite faster than previous methods reported. Three functions, viz., miniaturization, amorphization and recrystallization were found to take effect concurrently during this one-pot process. The dynamic balance between these three functions was achieved by adjusting the milling period and temperature, which lead to the tuning of zeolite A particle size. Particle size and crystallinity of the zeolite A nanocrystals were confirmed by X-ray diffraction, scanning electron microscopy, transmission electron microscopy and water adsorption-desorption. This work presents a pioneering advancement in this field of nanosized zeolites, and will facilitate the mass production as well as boost the wide applications of nanosized zeolites. PMID- 27378144 TI - Impact of Hospital Teaching Status on Mortality, Length of Stay and Cost Among Patients With Cardiac Arrest in the United States. AB - Limited data exist regarding the in-hospital outcomes in patients with cardiac arrest (CA) in teaching versus nonteaching hospital settings. Using the Nationwide (National) Inpatient Sample (2008 to 2012), 731,107 cases of CA were identified using International Classification of Diseases, Ninth Edition codes. Among these patients, 348,368 (47.6%) were managed in teaching hospitals and 376,035 (51.4%) in nonteaching hospitals. Patients in teaching hospitals with CA were younger (62.42 vs 68.08 years old), had less co-morbidities (p <0.001), were less likely to be white (54.6% vs 65.5%) and more likely to be uninsured (9.1% vs 7.6%). Mortality in patients with CA was significantly lower in teaching hospitals than in nonteaching hospitals (55.3% vs 58.8%; all p <0.001). The mortality remained significantly lower after adjusting for baseline patient and hospital characteristics (odds ratio 0.917, CI 0.899 to 0.937, p <0.001). However, the survival benefit was no longer present after adjusting for in hospital procedures (OR 0.997, CI 0.974 to 1.02, p = 0.779). In conclusion, teaching status of the hospital was associated with decreased in-hospital mortality in patients with CA. The differences in mortality disappeared after adjusting for in-hospital procedures, indicating that routine application of novel therapeutic methods in patients with CA in teaching hospitals could translate into improved survival outcomes. PMID- 27378146 TI - A chromosome 16p13.11 microduplication causes hyperactivity through dysregulation of miR-484/protocadherin-19 signaling. AB - Chromosome 16p13.11 microduplication is a risk factor associated with various neurodevelopmental disorders such as attention-deficit/hyperactivity disorder, intellectual disabilities, developmental delay and autistic spectrum disorder. The underlying molecular mechanism of this genetic variation remained unknown, but its core genetic locus-conserved across mice and humans-contains seven genes. Here, we generated bacterial artificial chromosome-transgenic mice carrying a human 16p13.11 locus, and these mice showed the behavioral hyperactivity phenotype. We identified miR-484 as the responsible gene using a combination of expression and functional analyses. Mature miR-484 was expressed during active cortical neurogenesis, and overexpression of miR-484 decreased proliferation and increased neural progenitor differentiation in vivo. Luciferase screening identified the 3'-untranslated region of protocadherin-19 (Pcdh19) as a target of miR-484. The effect of miR-484 on neurogenesis was rescued by ectopic PCDH19 expression. These results demonstrate that miR-484 promotes neurogenesis by inhibiting PCDH19. Dysregulation of neurogenesis by imbalanced miR-484/PCDH19 expression contributes to the pathogenesis of 16p13.11 microduplication syndrome. PMID- 27378148 TI - Prostate Cancer-Associated Kallikrein-Related Peptidase 4 Activates Matrix Metalloproteinase-1 and Thrombospondin-1. AB - Prostate cancer metastasis to bone is terminal; thus, novel therapies are required to prevent end-stage disease. Kallikrein-related peptidase 4 (KLK4) is a serine protease that is overproduced in localized prostate cancer and is abundant in prostate cancer bone metastases. In vitro, KLK4 induces tumor-promoting phenotypes; however, the underlying proteolytic mechanism is undefined. The protein topography and migration analysis platform (PROTOMAP) was used for high depth identification of KLK4 substrates secreted by prostate cancer bone metastasis-derived PC-3 cells to delineate the mechanism of KLK4 action in advanced prostate cancer. Thirty-six putative novel substrates were determined from the PROTOMAP analysis. In addition, KLK4 cleaved the established substrate, urokinase-type plasminogen activator, thus validating the approach. KLK4 activated matrix metalloproteinase-1 (MMP1), a protease that promotes prostate tumor growth and metastasis. MMP1 was produced in the tumor compartment of prostate cancer bone metastases, highlighting its accessibility to KLK4 at this site. KLK4 further liberated an N-terminal product, with purported angiogenic activity, from thrombospondin-1 (TSP1) and cleaved TSP1 in an osteoblast-derived matrix. This is the most comprehensive analysis of the proteolytic action of KLK4 in an advanced prostate cancer model to date, highlighting KLK4 as a potential multifunctional regulator of prostate cancer progression. PMID- 27378150 TI - Production of Ultracold 87 Rb133 Cs in the Absolute Ground State: Complete Characterisation of the Stimulated Raman Adiabatic Passage Transfer. AB - We present the production of ultracold 87 RbCs molecules in the electronic, rovibrational and hyperfine ground state, using stimulated Raman adiabatic passage to transfer the molecules from a weakly bound Feshbach state. We measure one-way transfer efficiencies of 92(1)% and fully characterise the strengths and linewidths of the transitions used. We model the transfer, including a Monte Carlo simulation of the laser noise, and find this matches well with both the transfer efficiency and our previous measurements of the laser linewidth and frequency stability. PMID- 27378149 TI - Andrographolide ameliorates diabetic nephropathy by attenuating hyperglycemia mediated renal oxidative stress and inflammation via Akt/NF-kappaB pathway. AB - Diabetic nephropathy (DN) is characterized by proliferation of mesangial cells, mesangial hypertrophy and extracellular matrix (ECM) accumulation. Our recent study found that andrographolide inhibited high glucose-induced mesangial cell proliferation and fibronectin expression through inhibition of AP-1 pathway. However, whether andrographolide has reno-protective roles in DN has not been fully elucidated. Here, we studied the pharmacological effects of andrographolide against the progression of DN and high glucose-induced mesangial dysfunction. Diabetes was induced in C57BL/6 mice by intraperitoneal injection of streptozotocin (STZ). After 1 weeks after STZ injection, normal diet was substituted with a high-fat diet (HFD). Diabetic mice were intraperitoneal injected with andrographolide (2 mg/kg, twice a week). After 8 weeks, functional and histological analyses were carried out. Parallel experiments uncovering the molecular mechanism by which andrographolide prevents from DN was performed in mesangial cells. Andrographolide inhibited the increases in fasting blood glucose, triglyceride, kidney/body weight ratio, blood urea nitrogen, serum creatinine and 24-h albuminuria in diabetic mice. Andrographolide also prevented renal hypertrophy and ECM accumulation. Furthermore, andrographolide markedly attenuated NOX1 expression, ROS production and pro-inflammatory cytokines as well. Additionally, andrographolide inhibited Akt/NF-kappaB signaling pathway. These results demonstrate that andrographolide is protective against the progression of experimental DN by inhibiting renal oxidative stress, inflammation and fibrosis. PMID- 27378147 TI - Altered proliferation and networks in neural cells derived from idiopathic autistic individuals. AB - Autism spectrum disorders (ASD) are common, complex and heterogeneous neurodevelopmental disorders. Cellular and molecular mechanisms responsible for ASD pathogenesis have been proposed based on genetic studies, brain pathology and imaging, but a major impediment to testing ASD hypotheses is the lack of human cell models. Here, we reprogrammed fibroblasts to generate induced pluripotent stem cells, neural progenitor cells (NPCs) and neurons from ASD individuals with early brain overgrowth and non-ASD controls with normal brain size. ASD-derived NPCs display increased cell proliferation because of dysregulation of a beta catenin/BRN2 transcriptional cascade. ASD-derived neurons display abnormal neurogenesis and reduced synaptogenesis leading to functional defects in neuronal networks. Interestingly, defects in neuronal networks could be rescued by insulin growth factor 1 (IGF-1), a drug that is currently in clinical trials for ASD. This work demonstrates that selection of ASD subjects based on endophenotypes unraveled biologically relevant pathway disruption and revealed a potential cellular mechanism for the therapeutic effect of IGF-1. PMID- 27378151 TI - Molecular biosignatures reveal common benthic microbial sources of organic matter in ooids and grapestones from Pigeon Cay, The Bahamas. AB - Ooids are sedimentary grains that are distributed widely in the geologic record. Their formation is still actively debated, which limits our understanding of the significance and meaning of these grains in Earth's history. Central questions include the role played by microbes in the formation of ooids and the sources of ubiquitous organic matter within ooid cortices. To address these issues, we investigated the microbial community composition and associated lipids in modern oolitic sands at Pigeon Cay on Cat Island, The Bahamas. Surface samples were taken along a transect from the shallow, turbulent surf zone to calmer, deeper water. Grains transitioned from shiny and abraded ooids in the surf zone, to biofilm-coated ooids at about 3 m water depth. Further offshore, grapestones (cemented aggregates of ooids) dominated. Benthic diatoms and Proteobacteria dominated biofilms. Taxa that may promote carbonate precipitation were abundant, particularly those associated with sulfur cycling. Compared to the lipids associated with surface biofilms, relict lipids bound within carbonate exhibited remarkably similar profiles in all grain types. The enhanced abundance of methyl branched fatty acids and beta-hydroxy fatty acids, 1-O-monoalkyl glycerol ethers and hopanoids bound within ooid and grapestone carbonate confirms a clear association of benthic sedimentary bacteria with these grains. Lipids bound within ooid cortices also contain molecular indicators of microbial heterotrophic degradation of organic matter, possibly in locally reducing conditions. These included the loss of labile unsaturated fatty acids, enhanced long-chain fatty acids/short-chain fatty acids, enriched stable carbon isotopes ratios of fatty acids, and very high stanol/stenol ratios. To what extent some of these molecular signals are derived from later heterotrophic endolithic activity remains to be fully resolved. We speculate that some ooid carbonate forms in microbial biofilms and that early diagenetic degradation of biofilms may also play a role in early stage carbonate precipitation around ooids. PMID- 27378153 TI - A structural equation model of soil metal bioavailability to earthworms: confronting causal theory and observations using a laboratory exposure to field contaminated soils. AB - Structural equation models (SEM) are increasingly used in ecology as multivariate analysis that can represent theoretical variables and address complex sets of hypotheses. Here we demonstrate the interest of SEM in ecotoxicology, more precisely to test the three-step concept of metal bioavailability to earthworms. The SEM modeled the three-step causal chain between environmental availability, environmental bioavailability and toxicological bioavailability. In the model, each step is an unmeasured (latent) variable reflected by several observed variables. In an exposure experiment designed specifically to test this SEM for Cd, Pb and Zn, Aporrectodea caliginosa was exposed to 31 agricultural field contaminated soils. Chemical and biological measurements used included CaC12 extractable metal concentrations in soils, free ion concentration in soil solution as predicted by a geochemical model, dissolved metal concentration as predicted by a semi-mechanistic model, internal metal concentrations in total earthworms and in subcellular fractions, and several biomarkers. The observations verified the causal definition of Cd and Pb bioavailability in the SEM, but not for Zn. Several indicators consistently reflected the hypothetical causal definition and could thus be pertinent measurements of Cd and Pb bioavailability to earthworm in field-contaminated soils. SEM highlights that the metals present in the soil solution and easily extractable are not the main source of available metals for earthworms. This study further highlights SEM as a powerful tool that can handle natural ecosystem complexity, thus participating to the paradigm change in ecotoxicology from a bottom-up to a top-down approach. PMID- 27378152 TI - Comparison of fipronil sources in North Carolina surface water and identification of a novel fipronil transformation product in recycled wastewater. AB - Fipronil is a phenylpyrazole insecticide that is widely used in residential and agricultural settings to control ants, roaches, termites, and other pests. Fipronil and its transformation products have been found in a variety of environmental matrices, but the source[s] which makes the greatest contribution to fipronil in surface water has yet to be determined. A sampling effort designed to prioritize known fipronil inputs (golf courses, residential areas, biosolids application sites and wastewater facilities) was conducted in North Carolina to learn more about the origins of fipronil in surface water. High resolution mass spectrometry (HRMS) analysis indicated that fipronil and its known derivatives were routinely present in all samples, but concentrations were substantially elevated near wastewater treatment plant outfalls (range 10-500ng/L combined), suggesting that they predominate as environmental sources. Corresponding recycled wastewater samples, which were treated with NaOCl for disinfection, showed disappearance of fipronil and all known degradates. HRMS and nuclear magnetic resonance (NMR) analysis techniques were used to determine that all fipronil related compounds are oxidized to a previously unidentified fipronil sulfone chloramine species in recycled wastewater. The implications of the presence of a new fipronil-related compound in recycled wastewater need to be considered. PMID- 27378154 TI - Prediction of fish and sediment mercury in streams using landscape variables and historical mining. AB - Widespread mercury (Hg) contamination of aquatic systems in the Sierra Nevada of California, U.S., is associated with historical use to enhance gold (Au) recovery by amalgamation. In areas affected by historical Au mining operations, including the western slope of the Sierra Nevada and downstream areas in northern California, such as San Francisco Bay and the Sacramento River-San Joaquin River Delta, microbial conversion of Hg to methylmercury (MeHg) leads to bioaccumulation of MeHg in food webs, and increased risks to humans and wildlife. This study focused on developing a predictive model for THg in stream fish tissue based on geospatial data, including land use/land cover data, and the distribution of legacy Au mines. Data on total mercury (THg) and MeHg concentrations in fish tissue and streambed sediment collected during 1980-2012 from stream sites in the Sierra Nevada, California were combined with geospatial data to estimate fish THg concentrations across the landscape. THg concentrations of five fish species (Brown Trout, Rainbow Trout, Sacramento Pikeminnow, Sacramento Sucker, and Smallmouth Bass) within stream sections were predicted using multi-model inference based on Akaike Information Criteria, using geospatial data for mining history and landscape characteristics as well as fish species and length (r(2)=0.61, p<0.001). Including THg concentrations in streambed sediment did not improve the model's fit, however including MeHg concentrations in streambed sediment, organic content (loss on ignition), and sediment grain size resulted in an improved fit (r(2)=0.63, p<0.001). These models can be used to estimate THg concentrations in stream fish based on landscape variables in the Sierra Nevada in areas where direct measurements of THg concentration in fish are unavailable. PMID- 27378155 TI - Infant and mother related outcomes from exposure to metals with endocrine disrupting properties during pregnancy. AB - BACKGROUND: Endocrine-related adverse health effects from exposure to heavy metals such as lead, arsenic, cadmium, and mercury are yet to be adequately described. The purpose of this review was to gain insight into maternal exposure to heavy metals, and to identify potential endocrine-related adverse health effects in the mother and the infant. METHODS: Relevant databases were searched for original research reports and a total of 46 articles were retained for scrutiny. Required data was extracted from these studies and their methodology was assessed. RESULTS: Impaired fetal growth was observed from exposure to all endocrine disrupting metals, while exposure to lead and arsenic were associated with spontaneous abortion, stillbirth and neonatal deaths. Maternal exposure to arsenic was associated with impaired glucose tolerance in these mothers. CONCLUSION: Impaired fetal growth, fetal loss, and neonatal deaths were significantly associated with heavy metals exposure during pregnancy; however, hypertension and gestational diabetes require further investigation. PMID- 27378156 TI - Cell-sized liposome doublets reveal active tension build-up driven by acto-myosin dynamics. AB - Cells modulate their shape to fulfill specific functions, mediated by the cell cortex, a thin actin shell bound to the plasma membrane. Myosin motor activity, together with actin dynamics, contributes to cortical tension. Here, we examine the individual contributions of actin polymerization and myosin activity to tension increase with a non-invasive method. Cell-sized liposome doublets are covered with either a stabilized actin cortex of preformed actin filaments, or a dynamic branched actin network polymerizing at the membrane. The addition of myosin II minifilaments in both cases triggers a change in doublet shape that is unambiguously related to a tension increase. Preformed actin filaments allow us to evaluate the effect of myosin alone while, with dynamic actin cortices, we examine the synergy of actin polymerization and myosin motors in driving shape changes. Our assay paves the way for a quantification of tension changes triggered by various actin-associated proteins in a cell-sized system. PMID- 27378157 TI - Chronic impedance spectroscopy of an endovascular stent-electrode array. AB - OBJECTIVE: Recently, we reported a minimally invasive stent-electrode array capable of recording neural signals from within a blood vessel. We now investigate the use of electrochemical impedance spectroscopy (EIS) measurements to infer changes occurring to the electrode-tissue interface from devices implanted in a cohort of sheep for up to 190 days. APPROACH: In a cohort of 15 sheep, endovascular stent-electrode arrays were implanted in the superior sagittal sinus overlying the motor cortex for up to 190 days. EIS was performed routinely to quantify viable electrodes for up to 91 days. An equivalent circuit model (ECM) was developed from the in vivo measurements to characterize the electrode-tissue interface changes occurring to the electrodes chronically implanted within a blood vessel. Post-mortem histological assessment of stent and electrode incorporation into the wall of the cortical vessels was compared to the electrical impedance measurements. MAIN RESULTS: EIS could be used to infer electrode viability and was consistent with x-ray analysis performed in vivo, and post-mortem evaluation. Viable electrodes exhibited consistent 1 kHz impedances across the 91 day measurement period, with the peak resistance frequency for the acquired data also stable over time. There was a significant change in 100 Hz phase angles, increasing from -67.8 degrees +/- 8.8 degrees at day 0 to -43.8 degrees +/- 0.8 degrees at day 91, which was observed to stabilize after eight days. ECM's modeled to the data suggested this change was due to an increase in the capacitance of the electrode-tissue interface. This was supported by histological assessment with >85% of the implanted stent struts covered with neointima and incorporated into the blood vessel within two weeks. CONCLUSION: This work demonstrated that EIS could be used to determine the viability of electrode implanted chronically within a blood vessel. Impedance measurements alone were not observed to be a useful predictor of alterations occurring at the electrode tissue interface. However, measurement of 100 Hz phase angles was in good agreement with the capacitive changes predicted by the ECM and consistent with suggestions that this represents protein absorption on the electrode surface. 100 Hz phase angles stabilized after 8 days, consistent with histologically assessed samples. SIGNIFICANCE: These findings demonstrate the potential application of this technology for use as a chronic neural recording system and indicate the importance of conducting EIS as a measure to identify viable electrodes and changes occurring at the electrode-tissue interface. PMID- 27378158 TI - A pre-operative clinical model to predict microvascular invasion and long-term outcome after resection of hepatocellular cancer: The Australian experience. AB - BACKGROUND: Hepatocellular cancer (HCC) is a leading cause of mortality worldwide. Liver resection or transplantation offer the best chance of long-term survival. The aim of this study was to perform a survival and prognostic factor analysis on patients who underwent resection of HCC at two major tertiary referral hospitals, and to investigate a pre-operative prediction model for microvascular invasion (MVI). METHODS: Clinico-pathological and survival data were collected from all patients who underwent liver resection for HCC at two tertiary referral centres (Royal North Shore/North Shore Private Hospitals and Westmead Hospital) from 1998 to 2012. An overall and disease-free survival analysis was performed and a predictive model for MVI identified. RESULTS: The total number of patients in this series was 125 and the 5-year overall and disease-free survival rates were 56% and 37%, respectively. MVI was the only factor to be independently associated with a poor prognosis on both overall and disease-free survival. Age >=64 years, a serum alpha-fetoprotein (AFP) >=400 ng/ml (*40 above normal) and tumor size >=50 mm were independently associated with MVI. An MVI prediction model using these three pre-operative factors provides a good assessment of the risk of MVI. CONCLUSION: MVI in the resected specimen of patients with HCC is associated with a poor prognosis. A preoperative MVI prediction model offers a useful way to identify patients at risk of relapse. However, more precise predictive models using molecular and genetic variables are needed to improve selection of patients most suitable for radical surgical treatment. PMID- 27378159 TI - Intraoperative Near-Infrared Fluorescence Imaging using indocyanine green in colorectal carcinomatosis surgery: Proof of concept. AB - PURPOSES: This study assesses the value of using Intraoperative Near Infrared Fluorescence Imaging and Indocyanine green to detect colorectal carcinomatosis during oncological surgery. In colorectal carcinomatosis cancer, two of the most important prognostic factors are completeness of staging and completeness of cytoreductive surgery. Presently, intraoperative assessment of tumoral margins relies on palpation and visual inspection. The recent introduction of Near Infrared fluorescence image guidance provides new opportunities for surgical roles, particularly in cancer surgery. METHODS: The study was a non-randomized, monocentric, pilot "ex vivo" blinded clinical trial validated by the ethical committee of University Hospital of Saint Etienne. Ten patients with colorectal carcinomatosis cancer scheduled for cytoreductive surgery were included. Patients received 0.25 mg/kg of Indocyanine green intravenously 24 h before surgery. A Near Infrared camera was used to detect "ex-vivo" fluorescent lesions. RESULTS: There was no surgical mortality. Each analysis was done blindly. In a total of 88 lesions analyzed, 58 were classified by a pathologist as cancerous and 30 as non cancerous. Among the 58 cancerous lesions, 42 were correctly classified by the Intraoperative Near-Infrared camera (sensitivity of 72.4%). Among the 30 non cancerous lesions, 18 were correctly classified by the Intraoperative Near Infrared camera (specificity of 60.0%). CONCLUSIONS: Near Infrared fluorescence imaging is a promising technique for intraoperative tumor identification. It could help the surgeon to determine resection margins and reduce the risk of locoregional recurrence. PMID- 27378160 TI - Is aortic lymphadenectomy indicated in locally advanced cervical cancer after neoadjuvant chemotherapy followed by radical surgery? A retrospective study on 261 women. AB - OBJECTIVES: The aim of this study was to estimate the rate of aortic lymph nodes (LN) metastases/recurrences among patients affected by locally advanced stage cancer patients (LACC), treated with neoadjuvant chemotherapy (NACT) and radical surgery. METHODS: Retrospective evaluation of consecutive 261 patients affected by LACC (stage IB2-IIB), treated with NACT followed by radical surgery at National Cancer Institute, Milan, Italy, between 1990 and 2011. RESULTS: Stage at presentation included stage IB2, IIA and IIB in 100 (38.3%), 50 (19.2%) and 111 (42.5%) patients, respectively. Squamous cell carcinoma accounted for more than 80%, followed by adenocarcinoma or adenosquamous cancers (20%). Overall, 56 women (21.5%) had LN metastases. Four out of 83 women (5%) who underwent both pelvic and aortic LN dissection had aortic LN metastases, and all women had concomitant pelvic and aortic LN metastases. Only one woman out of 178 (0.5%) who underwent pelvic lymphadenectomy only, had an aortic LN recurrence. Overall 2% of women (5/261) had aortic LN metastases/recurrence. CONCLUSIONS: Our data suggest that aortic lymphadenectomy at the time of surgery is not routinely indicated in LACC after NACT, but should reserved in case of bulky LN in both pelvic and/or aortic area. The risk of isolated aortic LN relapse is negligible. Further prospective studies are warranted. PMID- 27378161 TI - Surgeon volume impact on outcomes and cost of adrenal surgeries. AB - INTRODUCTION: The number of adrenal surgeries performed in the United Stated is continuing to increase. Identifying factors associated with favorable outcomes can have a major impact on cost-differences. We aim to assess the impact of surgeon volume on both clinical outcomes and cost following adrenal surgery. MATERIALS AND METHODS: A cross-sectional analysis was performed utilizing data from the Nationwide Inpatient Sample, 2003-2009. Surgeon volumes included (adrenalectomies/year): low-volume (1), intermediate-volume (2-6), and high volume (>=7). RESULTS: A total of 7045 patients were included. Surgeries performed by low-volume surgeons were associated with a higher risk of postoperative complications [OR: 1.66, 95% CI: (1.23, 2.24)]. During the study period, if all operations performed by low-volume surgeons were selectively referred to intermediate-volume surgeons, a 7.7% cost savings would have been incurred. Potential savings were even higher (8.1%) if the operations had been performed by the high-volume surgeons. With the conservative assumption that there are 5000 adrenalectomies per year in the United States, the high-volume surgeons would produce savings of $8.8 million over a span of 14 years. CONCLUSION: A surgeon's expertise is associated with favorable outcomes. Our model estimates that considerable cost savings are attainable with appropriate referrals to high volume endocrine surgeons. PMID- 27378163 TI - Flexible All-organic, All-solution Processed Thin Film Transistor Array with Ultrashort Channel. AB - Shrinking the device dimension has long been the pursuit of the semiconductor industry to increase the device density and operation speed. In the application of thin film transistors (TFTs), all-organic TFT arrays made by all-solution process are desired for low cost and flexible electronics. One of the greatest challenges is how to achieve ultrashort channel through a cost-effective method. In our study, ultrashort-channel devices are demonstrated by direct inkjet printing conducting polymer as source/drain and gate electrodes without any complicated substrate's pre-patterning process. By modifying the substrate's wettability, the conducting polymer's contact line is pinned during drying process which makes the channel length well-controlled. An organic TFT array of 200 devices with 2 MUm channel length is fabricated on flexible substrate through all-solution process. The simple and scalable process to fabricate high resolution organic transistor array offers a low cost approach in the development of flexible and wearable electronics. PMID- 27378162 TI - The effect of peer-group size on the delivery of feedback in basic life support refresher training: a cluster randomized controlled trial. AB - BACKGROUND: Students are largely providing feedback to one another when instructor facilitates peer feedback rather than teaching in group training. The number of students in a group affect the learning of students in the group training. We aimed to investigate whether a larger group size increases students' test scores on a post-training test with peer feedback facilitated by instructor after video-guided basic life support (BLS) refresher training. Students' one rescuer adult BLS skills were assessed by a 2-min checklist-based test 1 year after the initial training. METHODS: A cluster randomized controlled trial was conducted to evaluate the effect of student number in a group on BLS refresher training. Participants included 115 final-year medical students undergoing their emergency medicine clerkship. The median number of students was 8 in the large groups and 4 in the standard group. The primary outcome was to examine group differences in post-training test scores after video-guided BLS training. Secondary outcomes included the feedback time, number of feedback topics, and results of end-of-training evaluation questionnaires. RESULTS: Scores on the post training test increased over three consecutive tests with instructor-led peer feedback, but not differ between large and standard groups. The feedback time was longer and number of feedback topics generated by students were higher in standard groups compared to large groups on the first and second tests. The end of-training questionnaire revealed that the students in large groups preferred the smaller group size compared to their actual group size. CONCLUSIONS: In this BLS refresher training, the instructor-led group feedback increased the test score after tutorial video-guided BLS learning, irrespective of the group size. A smaller group size allowed more participations in peer feedback. PMID- 27378164 TI - The use of a multiple imputation method to investigate the trends in Histologic types of lung cancer in Songkhla province, Thailand, 1989-2013. AB - BACKGROUND: The incidence of lung cancer in many parts of the country as shown in cancer registry statistics is not decreasing. The incidence of adenocarcinoma (ADCA) in Songkhla is now higher than that of squamous cell carcinoma (SCC) in both sexes. The percentage of the unknown histologic type of lung cancer in Songkhla is around 30 %. The objective of this study is to estimate trends in incidence of the two major histologic types of lung cancer: SCC and ADCA, in Songkhla province of Thailand from 1989 to 2013. METHODS: Age-standardized incidence rates (ASR) were used to compare and described the trends in both major types of cancers. Multinomial logistic regression models were used to impute unknown histological cancer types using a multiple imputation (MI) method to account for the high percentage of unknown histology. RESULTS: The multinomial predictive model for major types of lung cancer in Songkhla consisted of sex, age, year of diagnosis, and place of residence. After MI, the number of cases with both SCC and ADCA in both sexes increased by one-third of the number of cases with originally known histology. The increasing trends were observed in ADCA in both sexes while SCC in males was stable and in females was decreasing. CONCLUSIONS: A rapid increase in the incidence of ADCA was found while the incidence of SCC in males showed no significant change and it was declining in females. These results warrant an investigation into risk factors other than cigarette smoking. The number of cases has limited use when the age structure of the population under study is changing. Year of diagnosis was one of the predictors in the MI model. PMID- 27378165 TI - Predictive Synthesis of Freeform Carbon Nanotube Microarchitectures by Strain Engineered Chemical Vapor Deposition. AB - High-throughput fabrication of microstructured surfaces with multi-directional, re-entrant, or otherwise curved features is becoming increasingly important for applications such as phase change heat transfer, adhesive gripping, and control of electromagnetic waves. Toward this goal, curved microstructures of aligned carbon nanotubes (CNTs) can be fabricated by engineered variation of the CNT growth rate within each microstructure, for example by patterning of the CNT growth catalyst partially upon a layer which retards the CNT growth rate. This study develops a finite-element simulation framework for predictive synthesis of complex CNT microarchitectures by this strain-engineered growth process. The simulation is informed by parametric measurements of the CNT growth kinetics, and the anisotropic mechanical properties of the CNTs, and predicts the shape of CNT microstructures with impressive fidelity. Moreover, the simulation calculates the internal stress distribution that results from extreme deformation of the CNT structures during growth, and shows that delamination of the interface between the differentially growing segments occurs at a critical shear stress. Guided by these insights, experiments are performed to study the time- and geometry depended stress development, and it is demonstrated that corrugating the interface between the segments of each microstructure mitigates the interface failure. This study presents a methodology for 3D microstructure design based on "pixels" that prescribe directionality to the resulting microstructure, and show that this framework enables the predictive synthesis of more complex architectures including twisted and truss-like forms. PMID- 27378166 TI - Foreign body removal is getting "cooler". AB - Foreign body removal is commonly performed with the rigid bronchoscope. However, based on recent literature, extraction with the flexible bronchoscope has increased in popularity. Here, we discuss a new tool - the flexible cryoprobe - that may enhance foreign body retrieval in select patients and comment on the methods of foreign body extraction in the view of common clinical practice. Pediatr Pulmonol. 2016; 51:886-888. (c) 2016 Wiley Periodicals, Inc. PMID- 27378167 TI - Effects and molecular mechanism of chitosan-coated levodopa nanoliposomes on behavior of dyskinesia rats. AB - BACKGROUND: Chitosan, the N-deacetylated derivative of chitin, is a cationic polyelectrolyte due to the presence of amino groups, one of the few occurring in nature. The use of chitosan in protein and drug delivery systems is being actively researched and reported in the literature. RESULTS: In this study, we used chitosan-coated levodopa liposomes to investigate the behavioral character and the expression of phosphorylated extracellular signal-regulated kinase (ERK1/2), dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) and FosB/DeltaFosB in striatum of rat model of levodopa-induced dyskinesia (LID). We found that scores of abnormal involuntary movement (AIM) decreased significantly in liposome group (P < 0.05), compared with levodopa group. Levels of phospho ERK1/2, phospho-Thr34 DARPP-32 and FosB/DeltaFosB in striatum decreased significantly in liposome group lesion side compared with levodopa group (P < 0.05). However, both of two groups above have significantly differences compared with the control group (P < 0.05). CONCLUSION: Chitosan-coated levodopa liposomes may be useful in reducing dyskinesias inducing for Parkinson disease. The mechanism might be involved the pathway of signaling molecular phospho-ERK1/2, phospho-Thr34 DARPP-32 and DeltaFosB in striatum. PMID- 27378169 TI - Prickle1 promotes focal adhesion disassembly in cooperation with the CLASP LL5beta complex in migrating cells. AB - Prickle is known to be involved in planar cell polarity, including convergent extension and cell migration; however, the detailed mechanism by which Prickle regulates cellular functions is not well understood. Here, we show that Prickle1 regulates front-rear polarization and migration of gastric cancer MKN1 cells. Prickle1 preferentially accumulated at the cell retraction site in close proximity to paxillin at focal adhesions. Prickle1 dynamics correlated with those of paxillin during focal adhesion disassembly. Furthermore, Prickle1 was required for focal adhesion disassembly. CLASPs (of which there are two isoforms, CLASP1 and CLASP2, in mammals) and LL5beta (also known as PHLDB2) have been reported to form a complex at cell edges and to control microtubule-dependent focal adhesion disassembly. Prickle1 was associated with CLASPs and LL5beta, and was required for the LL5beta-dependent accumulation of CLASPs at the cell edge. Knockdown of CLASPs and LL5beta suppressed Prickle1-dependent cell polarization and migration. Prickle1 localized to the membrane through its farnesyl moiety, and the membrane localization was necessary for Prickle1 to regulate migration, to bind to CLASPs and LL5beta, and to promote microtubule targeting of focal adhesions. Taken together, these results suggest that Prickle1 promotes focal adhesion disassembly during the retraction processes of cell polarization and migration. PMID- 27378168 TI - 8q21.11 microdeletion in two patients with syndromic peters anomaly. AB - Peters anomaly is a form of anterior segment dysgenesis characterized by central ocular opacity and corneo-lenticular adhesions. Isolated and syndromic Peters anomaly can be observed and demonstrate significant genetic heterogeneity. We report the identification of overlapping 8q21.11 deletions in two patients with syndromic Peters anomaly via whole exome sequencing and chromosomal microarray analyses. Microdeletions of 8q21.11 were recently reported in 10 patients with highly variable phenotypes involving craniofacial features, ptosis, intellectual disability, abnormalities of the hands/feet and other defects; sclerocornea and/or microphthalmia were reported in three cases. The two additional cases presented in this report expand the phenotypic spectrum of 8q21.11 microdeletions to include Peters anomaly (seen in both patients) and persistent primary dentition (seen in one patient with a larger deletion). The two novel deletions include the ZFHX4 and PEX2 genes, which were also affected in all three previous cases involving ocular anomalies. Screening of the remaining alleles of ZFHX4 and PEX2 did not identify any additional likely pathogenic variants in either patient, suggesting a dominant mechanism (haploinsufficiency) for the identified deletion. This report provides further insight into the phenotypes associated with 8q21.11 deletions and, for the first time, reports Peters anomaly as an additional ocular feature; screening for copy number variations of the 8q21.11 region should be considered in patients with Peters anomaly and related syndromic features. (c) 2016 Wiley Periodicals, Inc. PMID- 27378170 TI - Conditional ablation of TGF-beta signaling inhibits tumor progression and invasion in an induced mouse bladder cancer model. AB - The role of transforming growth factor-beta (TGF-beta) signaling in cancer progression is still under debate. To determine the function of TGF-beta signaling in bladder cancer progression, we conditionally knocked out the Tgfbr2 in mouse model after a N-butyl-N-4-hydroxybutyl Nitrosamine induced bladder carcinogenesis. We found the ablation of TGF-beta signaling could inhibit the cancer cell proliferation, cancer stem cell population and EMT, hence suppressed the invasive cancer progression, which is similar with the result of TGF-beta receptor I inhibitor treatment. These findings recognize the roles and mechanisms of TGF-beta signaling in bladder cancer progression in vivo for the first time. PMID- 27378171 TI - Yield and Clinical Utility of Next-Generation Sequencing in Selected Patients With Lung Adenocarcinoma. AB - BACKGROUND: Next-generation sequencing is available for assessing genomic alterations in non-small-cell lung cancer (NSCLC), although the performance characteristics and clinical utility has not been well characterized. This technique can be used to sequence hundreds of known cancer-associated genes. Our aim was to investigate the diagnostic success and clinically relevant results of extensive sequencing in NSCLC patients. PATIENTS AND METHODS: A case series of 49 NSCLC patients was used to determine the success of extended next-generation sequencing, record genomic alterations, and evaluate clinical utility. Data were collected in a retrospective review. Sequencing was performed using a hybridization capture of 3320 exons from 236 cancer-related genes and 47 introns of 19 genes applied to >=50 ng of DNA and sequenced to high, uniform coverage of 622 times. RESULTS: Sequencing was successful in 29 of 32 (91%) surgical/excisional specimens, and 12 of 17 (71%) nonsurgical specimens including an endoscopic forceps biopsy, core needle biopsies, fine-needle aspirates, and effusion cytologies. All 5 transthoracic core needle biopsies failed. A total of 179 genomic alterations (average 4.37 per tumor) were found. A total of 63 were clinically relevant (average 1.54 per tumor). The most frequently mutated genes were tumor protein p53, cyclin-dependent kinase inhibitor 2A, megalencephalic leukoencephalopathy with subcortical cysts 1, rapamycin-insensitive companion of mammalian target of rapamycin, epithelial growth factor receptor, SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 4, cyclin-dependent kinase inhibitor 2B, phosphatidylinositol-4,5 bisphosphate 3-kinase, catalytic subunit alpha, Kirsten rat sarcoma viral oncogene homolog, Erb-B2 receptor tyrosine kinase 2, Serine/Threonine Kinase 11, and NK2 Homeobox 1. Sequencing results led to a change in management in 7 of 49 cases (14.3%). CONCLUSION: Extended next-generation sequencing was performed successfully in 41 (83.7%) cases of NSCLC using a range of pathology specimens. Testing had the potential to affect treatment decisions in selected patients. PMID- 27378172 TI - Hypofractionated Intensity-Modulated Radiotherapy for Patients With Non-Small Cell Lung Cancer. AB - BACKGROUND: Alternative treatment regimens are needed for patients with non-small cell lung cancer (NSCLC) who cannot receive definitive treatment with concurrent chemoradiotherapy, surgery, or stereotactic ablative radiotherapy (SABR). PATIENTS AND METHODS: We report survival, patterns of failure and toxicity outcomes for patients with NSCLC who were not eligible for surgical resection, concurrent chemoradiotherapy, or SABR and underwent hypofractionated intensity modulated radiotherapy (IMRT). Kaplan-Meier survival analysis was used to evaluate the progression-free and overall survival. Competing risk analysis was used to evaluate in-field, locoregional, and distant failure. RESULTS: A total of 42 patients treated to 52.5 to 60 Gy in 15 fractions were included. Most of the patients had metastatic or recurrent disease (64%) and a relatively large, centrally located tumor burden (74%). The median follow-up period was 13 months (interquartile range, 6-18 months). All patients received the total prescribed dose. The median survival was 15.1 months. The overall and progression-free survival rates at 1 year were 63% and 22.5%, respectively. The pattern of failure was predominantly distant, with only 2% of patients experiencing isolated in field recurrence. The cumulative incidence of in-field failure at 6 and 12 months was 2.5% (95% confidence interval, 0.4%-15.6%) and 16.1% (95% confidence interval, 7.5%-34.7%), respectively. The risk of esophageal toxicity was associated with the esophageal mean dose, maximal point dose, and dose to the 5 cm3 volume. The risk of pneumonitis was associated with the lung mean dose and volume receiving 18 Gy. CONCLUSION: Hypofractionated IMRT without concurrent chemotherapy provides favorable rates of local control and survival for well selected patients with NSCLC who cannot tolerate standard definitive therapy. PMID- 27378173 TI - Clinical Implications of Isolated Bone Failure Without Systemic Disease Progression During EGFR-TKI Treatment. AB - BACKGROUND: We investigated the characteristics of patients with epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) who had experienced isolated progression of bone metastases without aggravation of extraskeletal organs during EGFR-tyrosine kinase inhibitor (TKI) treatment. MATERIALS AND METHODS: We retrospectively reviewed the data from 870 patients with EGFR-mutant NSCLC treated with EGFR-TKI from 2004 to 2014. Of these patients, 71 (8.2%), who had undergone radiation therapy to bone metastases because of skeletal-related events, impending skeletal-related events, or medically uncontrolled bone pain, were selected and defined as having bone failure (BF). BFs were classified into 2 categories according to the presence of accompanying disease progression in extraskeletal organs: isolated BF (IBF) and non-IBF. RESULTS: Of the 71 BF patients, 33 (46.5%) experienced IBF without aggravation of disease in extraskeletal organs. IBF was more frequent in the clinical benefit group (responders and stable for >= 6 months) than in nonclinical benefit group (54.4% vs. 14.3%; P = .007). IBF was also more frequent in those with good performance status (82.5% vs. 42.9%; P = .005) and 19 deletion (68.4% vs. 35.7%; P = .024). Female sex, good performance status, and clinical benefit from TKI were more frequent in patients with IBF than in those with non IBF (female sex, 69.7% vs. 44.7%; P = .034; Eastern Cooperative Oncology Group 0 or 1, 87.9% vs. 63.2%; P = .017; clinical benefit from TKI, 93.9% vs. 68.4%; P = .007). Clinical benefit from EGFR-TKI was an independent predictor of IBF (adjusted odds ratio, 6.647; 95% confidence interval, 1.328-33.262; P = .021). Patients with IBF tended to exhibit longer survival times from the initiation of the TKI (20.7 vs. 11.1 months; P = .2) and from the onset of BF (8.6 vs. 3.4 months; P = .186). CONCLUSION: IBF without systemic disease progression frequently occurs in patients with clinical benefits from EGFR-TKI and is associated with better survival. This finding requires future studies to explore the differential activity of EGFR-TKI in the bones over time or in preference to other organs. PMID- 27378174 TI - Neoadjuvant Oncogene-Targeted Therapy in Early Stage Non-Small-Cell Lung Cancer as a Strategy to Improve Clinical Outcome and Identify Early Mechanisms of Resistance. AB - Evaluations of resistance mechanisms to targeted treatments in non-small-cell lung cancer (NSCLC) are necessary for development of improved treatment after disease progression and to help delay progression of disease. Populations of cells that survive after initial treatment form the basis of resistance via outgrowth of resistant clones or activation of alternative signaling pathways. In this report we describe a clinical trial approach in which patients with epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), C-ros 1 proto-oncogene (ROS1), and hepatocyte growth factor receptor (MET) exon 14 alterations and early stage (IA-IIIA) NSCLC will be treated with induction EGFR tyrosine kinase inhibitor (TKI) or crizotinib, a TKI that inhibits ALK, ROS1, and MET. We will evaluate resected tumor samples for pathologic response to induction therapy, overall response rate, and disease-free survival. Additionally, we will assess patients for early evidence of resistance to targeted therapy in terms of activation of alternative signaling pathways and for identification of resistance clones in remnant cell populations. PMID- 27378175 TI - Optimizing Survival of Patients With Marginally Operable Stage IIIA Non-Small Cell Lung Cancer Receiving Chemoradiotherapy With or Without Surgery. AB - BACKGROUND: For marginally operable stage IIIA non-small-cell lung cancer (NSCLC), surgery might not be done as planned after neoadjuvant concurrent chemoradiotherapy (CCRT) for reasons (unresectable or medically inoperable conditions, or patient refusal). This study aims to investigate the outcomes of a phased CCRT protocol established to maximize the operability of marginally operable stage IIIA NSCLC and to care for reassessed inoperable patients, in comparison with continuous-course definitive CCRT. MATERIALS AND METHODS: Forty seven patients with marginally operable stage IIIA NSCLC receiving CCRT were included. Twenty-eight patients were treated with our phased CCRT protocol, including neoadjuvant CCRT followed by surgery (group A, n = 16) or, for reassessed inoperable patients, maintenance chemotherapy and split-course CCRT boost (group B, n = 12). The other 19 were treated with continuous-course definitive CCRT (group C). Overall survival (OS) and progression-free survival (PFS) were analyzed. RESULTS: Among all, median OS and PFS were 35.6 and 12.8 months, respectively (median follow-up, 22.3 months). The median OS of group A (not reached) was better than that of group B (34.4 months) and group C (15.2 months) (P = .009). On multivariate analysis, performance status 0 to 1 (hazard ratio [HR], 0.026; P < .001), adenocarcinoma (HR, 0.156; P = .003), and group A (HR, 0.199; P = .033) were independent prognostic factors. The OS of group B (HR, 0.450; 95% confidence interval, 0.118-1.717; P = .243) was not statistically different from that of group C. CONCLUSIONS: For marginally operable stage IIIA NSCLC, our phased CCRT strategy may optimize survival by maximizing operability and maintain an acceptable survival for reassessed inoperable patients by split course CCRT boost following maintenance chemotherapy. PMID- 27378177 TI - Bipolar and related disorders in DSM-5 and ICD-10. AB - Bipolar disorders are a group of psychiatric disorders with profound negative impact on affected patients. Even if their symptomatology has long been recognized, diagnostic criteria have changed over time and diagnosis often remains difficult. The Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), issued in May 2013, comprises several changes regarding the diagnosis of bipolar disorders compared to the previous edition. Diagnostic categories and criteria for bipolar disorders show some concordance with the internationally also widely used Tenth Edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). However, there are also major differences that are worth highlighting. The aim of the following text is to depict and discuss those. PMID- 27378176 TI - IRS1 deficiency protects beta-cells against ER stress-induced apoptosis by modulating sXBP-1 stability and protein translation. AB - Endoplasmic reticulum (ER) stress is among several pathological features that underlie beta-cell failure in the development of type 1 and type 2 diabetes. Adaptor proteins in the insulin/insulin-like-growth factor-1 signaling pathways, such as insulin receptor substrate-1 (IRS1) and IRS2, differentially impact beta cell survival but the underlying mechanisms remain unclear. Here we report that beta-cells deficient in IRS1 (IRS1KO) are resistant, while IRS2 deficiency (IRS2KO) makes them susceptible to ER stress-mediated apoptosis. IRS1KOs exhibited low nuclear accumulation of spliced XBP-1 due to its poor stability, in contrast to elevated accumulation in IRS2KO. The reduced nuclear accumulation in IRS1KO was due to protein instability of Xbp1 secondary to proteasomal degradation. IRS1KO also demonstrated an attenuation in their general translation status in response to ER stress revealed by polyribosomal profiling. Phosphorylation of eEF2 was dramatically increased in IRS1KO enabling the beta cells to adapt to ER stress by blocking translation. Furthermore, significantly high ER calcium (Ca(2+)) was detected in IRS1KO beta-cells even upon induction of ER stress. These observations suggest that IRS1 could be a therapeutic target for beta-cell protection against ER stress-mediated cell death by modulating XBP-1 stability, protein synthesis, and Ca(2+) storage in the ER. PMID- 27378178 TI - Determinants of neonatal mortality in rural and urban Nigeria: Evidence from a population-based national survey. AB - BACKGROUND: Significant reduction in the global burden of neonatal mortality was achieved through the millennium development goals. In Nigeria, however, only a marginal reduction was realized. This study assesses the rural-urban differences in neonatal mortality rate (NMR) and the associated risk factors in Nigeria. METHODS: The dataset from the 2013 Nigeria demographic and health survey (NDHS), disaggregated by rural-urban residence (n = 20 449 and 9935, respectively), was explored using univariate, bivariate, and multivariable analysis. Complex samples analysis was applied to adjust for the unequal selection probabilities due to the multi-stage cluster sampling method used in the 2013 NDHS. The adjusted relationship between the outcome and predictor variables was assessed on multi level logistic regression analysis. RESULTS: NMR for rural and urban populations was 36 and 28 deaths per 1000 live births, respectively. Risk factors in urban residence were lack of electricity access (adjusted OR [AOR], 1.555; 95%CI: 1.089 2.220), small birth size (as a proxy for low birthweight; AOR, 3.048; 95%CI: 2.047-4.537), and male gender (AOR, 1.666; 95%CI: 1.215-2.284). Risk factors in rural residence were small birth size (a proxy for low birthweight; AOR, 2.118; 95%CI: 1.600-2.804), and birth interval <2 years (AOR, 2.149; 95%CI: 1.760 2.624). Cesarean delivery was a risk factor both in rural (AOR, 5.038; 95%CI: 2.617-9.700) and urban Nigeria (AOR, 2.632; 95%CI: 1.543-4.489). CONCLUSIONS: Determinants of neonatal mortality were different in rural and urban Nigeria, and rural neonates had greater risk of mortality than their urban counterparts. PMID- 27378179 TI - The therapeutic effects of apigenin and dexamethasone on 5-fluorouracil-induced oral mucositis - a pilot study using a Syrian hamster model. AB - OBJECTIVE: Oral mucositis (OM) is a common complication of chemotherapy and radiotherapy. The aim of this study was to evaluate the effects of treating 5 fluorouracil-induced OM with apigenin and dexamethasone. METHODS: Thirty-six male Syrian hamsters were randomly assigned to one of three groups: control (50% acetic acid + 5-FU), 50% acetic acid + 5-FU + potassium Apigenin (KA), and 50% acetic acid + 5-FU + dexamethasone. The animals from each group were sacrificed 5, 7, 10, and 14 days after inducing the mucositis, and two samples collected from each animal, accounting a total of 72 samples. Macroscopic changes were assessed by histomorphometric analysis, with ulcers being assessed by imaging analysis and the number of inflammatory cells in the ulcerated region quantified in all periods through histomorphometric analysis (H&E). Furthermore, immunohistochemical changes were evaluated by proliferating cell nuclear antigen. RESULTS: All groups presented an increased inflammatory infiltrate after 7 days, compared to other evaluation times (P >= 0.05). There was significant difference between apigenin and control group in the 10-days period. Lower quantity of inflammatory cells in the apigenin-treated group in comparison with control group in the 7- and 10-days periods was observed (P < 0.05). No statistically significant difference was verified among the groups in 5- and 14-days periods. The healing process of the control group was slower than that of apigenin and dexamethasone-treated groups, with an overall significant difference between apigenin and the control group in the 10-days period. CONCLUSIONS: Apigenin treatment may enhance healing of OM induced by 5-fluorouracil, thus suggesting that more extensive research in this area may be useful to assess the role of agents of natural origin capable of preventing OM. Hence, further studies involving broader samples are need to confirm the therapeutic potential shown by this study. PMID- 27378180 TI - From facultative to obligatory parental care: Interspecific variation in offspring dependency on post-hatching care in burying beetles. AB - Studies on the evolution of parental care have focused primarily on the costs and benefits of parental care and the life-history attributes that favour it. However, once care evolves, offspring in some taxa appear to become increasingly dependent on their parents. Although offspring dependency is a central theme in family life, the evolutionary dynamics leading to it are not fully understood. Beetles of the genus Nicrophorus are well known for their elaborate biparental care, including provisioning of their young. By manipulating the occurrence of pre- or post-hatching care, we show that the offspring of three burying beetle species, N. orbicollis, N. pustulatus, and N. vespilloides, show striking variation in their reliance on parental care. Our results demonstrate that this variation within one genus arises through a differential dependency of larvae on parental feeding, but not on pre-hatching care. In N. pustulatus, larvae appear to be nutritionally independent of their parents, but in N. orbicollis, larvae do not survive in the absence of parental feeding. We consider evolutionary scenarios by which nutritional dependency may have evolved, highlighting the role of brood size regulation via infanticide in this genus. PMID- 27378182 TI - Exploring the Reactivity of N-Alkynylated Sulfoximines: Acid-Catalyzed Cyclizations. AB - N-Alkynylated sulfoximines undergo acid-promoted cyclization processes under mild reaction conditions. The transformations proceed in short reaction times affording sulfoximidoyl-functionalized naphtho[2,1-b]thiophenes or pyrrolo[1,2 a]quinolines in up to excellent yields. PMID- 27378181 TI - Macroalgae of Izmir Gulf: Dictyotaceae exhibit high in vitro anti-cancer activity independent from their antioxidant capabilities. AB - In this study, 24 marine macroalgae collected from the coastline of Izmir Gulf were examined for their antioxidant activities and their effects on cell proliferation. Crude extracts were obtained from samples with cold methanol extraction. Antioxidant activity was evaluated as 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging activity and total phenolic content (TPC); growth inhibitory effects of the extracts were determined by using WST-8. Amongst the species, Polysiphonia denuata (Rhodophyta) and Cystoseira species (Phaeophyceae) have been noticed by their high DPPH radical scavenging activities and TPCs. As expected, there was a strong correlation between these tests. Dictyota dichotoma (Phaeophyceae) showed the highest anti-cancer activity on MCF-7 cells with an IC50 of 17.2 ng mL-1. Flow cytometry analyses demonstrated that D. dichotoma methanolic extract strongly induced apoptosis. This extract exhibited moderate viability inhibition on MCF10A cells (IC50: 49.3 ng mL-1), suggesting a potential use of the extracts or its compounds for cancer therapy. There was no correlation between anti-cancer potential and antioxidant content of the extracts. PMID- 27378183 TI - Loss of function of NaPiIIa causes nephrocalcinosis and possibly kidney insufficiency. AB - BACKGROUND: Inherited metabolic disorders associated with nephrocalcinosis are rare conditions. The aim of this study was to identify the genetic cause of an Israeli-Arab boy from a consanguineous family with severe nephrocalcinosis and kidney insufficiency. METHODS: Clinical and biochemical data of the proband and family members were obtained from both previous and recent medical charts. Genomic DNA was isolated from peripheral blood cells. The coding sequence and splice sites of candidate genes (CYP24A1, CYP27B1, FGF23, KLOTHO, SLC34A3 and SLC34A1) were sequenced directly. Functional studies were performed in Xenopus laevis oocytes and in transfected opossum kidney (OK) cells. RESULTS: Our patient was identified as having nephrocalcinosis in utero, and at the age of 16.5 years, he had kidney insufficiency but no bone disease. Genetic analysis revealed a novel homozygous missense mutation, Arg215Gln, in SLC34A1, which encodes the renal sodium phosphate cotransporter NaPiIIa. Functional studies of the Arg215Gln mutant revealed reduced transport activity in Xenopus laevis oocytes and increased intracellular cytoplasmic accumulation in OK cells. CONCLUSIONS: Our findings show that dysfunction of the human NaPiIIa causes severe renal calcification that may eventually lead to reduced kidney function, rather than complications of phosphate loss. PMID- 27378184 TI - Ocean acidification leads to deformations of caudal vein angio-architecture in juvenile threespine stickleback, Gasterosteus aculeatus Linnaeus. PMID- 27378187 TI - Adaptation of the Cutaneous Microcirculation in Preterm Neonates. AB - OBJECTIVE: Transition from fetal to neonatal circulation is characterized by multiple hemodynamic changes. The role of the microcirculation in this process is underexposed. Visualizing the cutaneous microcirculation can help us understand peripheral perfusion in a noninvasive manner. METHODS: Cutaneous microcirculation of term and preterm infants born below 32 weeks of GA was measured in the first month of life using IDF imaging. Linear mixed modeling was used to identify clinical variables which influence the cutaneous microcirculation. RESULTS: Sixty preterm and 33 term infants were included. TVD of preterm infants significantly decreased in the first month of life (31.7 mm/mm(2) day 1 vs 27.9 mm/mm(2) day 28), but remained significantly higher compared to TVD of term infants on day 1 (25.8 mm/mm(2) ). Besides postnatal age, no clinical variables were associated with TVD. Infants born SGA had significantly higher TVD values directly after birth than those born appropriate for GA (35.4 mm/mm(2) vs 31.6 mm/mm(2) ; p = 0.015). CONCLUSIONS: TVD decreases in the first month after birth and is higher in preterm infants compared to those born term. Differences in antenatal oxygen exposure might explain the adaptation of the microcirculation. PMID- 27378185 TI - Vitamin D deficiency and its risk factors in Malaysian children with epilepsy. AB - OBJECTIVE: Long-term use of antiepileptic drugs (AEDs) is a significant risk factor for vitamin D deficiency in children with epilepsy. The aims of our study were to evaluate the prevalence and risk factors for vitamin D deficiency among Malaysian children with epilepsy. METHODS: Cross-sectional study of ambulant children with epilepsy on long-term AEDs for >1 year seen in three tertiary hospitals in Malaysia from April 2014 to April 2015. Detailed assessment of pubertal status, skin pigmentation, sunshine exposure behavior, physical activity, dietary vitamin D and calcium intake, anthropometric measurements and bone health blood tests (vitamin D, alkaline phosphatase, calcium, phosphate, and parathyroid hormone levels) were obtained on all patients. Vitamin D deficiency was defined as 25-hydroxy vitamin D [25(OH)D] levels <=35 nmol/L and insufficiency as 25(OH)D levels of 36-50 nmol/L. RESULTS: A total of 244 children (146 male) participated in the study. Ages ranged between 3.7 and 18.8 years (mean 12.3 years). 25(OH)D levels ranged between 7.5 and 140.9 nmol/L (mean 53.9 nmol/L). Vitamin D deficiency was identified in 55 patients (22.5%), and a further 48 (19.7%) had vitamin D insufficiency. Multivariate logistic regression analysis identified polytherapy >1 AED (odds ratio [OR] 2.16, 95% confidence interval [CI] 1.07-4.36), age >12 years (OR 4.16, 95% CI 1.13-15.30), Indian ethnicity (OR 6.97, 95% CI 2.48-19.55), sun exposure time 30-60 min/day (OR 2.44, 95% CI 1.05-5.67), sun exposure time <30 min/day (OR 3.83, 95% CI 1.61-9.09), and female (OR 2.61, 95% CI 1.31-5.20) as statistically significant (p < 0.05) risk factors for vitamin D deficiency. SIGNIFICANCE: Despite living in the tropics, a high proportion of Malaysian children with epilepsy are at risk of vitamin D deficiency. Targeted strategies including vitamin D supplementation and lifestyle advice of healthy sunlight exposure behavior should be implemented among children with epilepsy, particularly for those at high risk of having vitamin D deficiency. PMID- 27378188 TI - Pharmacokinetics, tissue distribution, excretion, and metabolite profiling of PEGylated rFIX (nonacog beta pegol, N9-GP) in rats. AB - Nonacog beta pegol (N9-GP) is a novel recombinant factor IX conjugated with a 40 kDa branched polyethylene glycol (PEG) to extend plasma half-life (t1/2) compared with native FIX, developed for the treatment of haemophilia B. This is the first time distribution, metabolism, and excretion data of N9-GP have been presented. ADME studies were performed using single i.v. doses of radiolabelled N9-GP administered to rats, focussing on the biological fate of the 40-kDa PEG. Results indicated that N9-GP-related radioactivity was distributed throughout the body, being most abundant in highly vascularised tissues, and with lowest levels seen in the central nervous system. N9-GP was cleared from plasma within 1week after dosing, while total radioactivity was eliminated more slowly, in a more pronounced biphasic manner. N9-GP seems to be cleared via receptor-mediated uptake (e.g., in the liver) or via the reticuloendothelial system with subsequent proteolysis. PEG is thereafter either cleared alongside the protein or released back into circulation. Furthermore, N9-GP-related radioactivity was excreted in both faeces and urine as 40kDa PEG and degradation products. Some PEG-related radioactivity (not in any particular organ) was present in the carcass 12weeks postdose, consistent with the long terminal elimination t1/2 of plasma radioactivity. As shown here for N9-GP, and previously for other protein-PEG conjugate products, disposition kinetics of conjugates and individual constituents appears to be compound specific. In addition to the size/structure of the PEG and protein moieties, protein-specific clearance pathways may contribute to the disposition of intact conjugate and PEG moiety. PMID- 27378190 TI - Using multiple hydrogen bonding cross-linkers to access reversibly responsive three dimensional graphene oxide architecture. AB - Three-dimensional (3D) graphene materials have attracted a lot of attention for efficiently utilizing inherent properties of graphene sheets. However, 3D graphene materials reported in the previous literature are constructed through covalent or weak non-covalent interactions, causing permanent structure/property changes. In this paper, a novel 3D graphene material of dynamic interactions between lamellas with 2-ureido-4[1H]-pyrimidinone as a supra-molecular motif has been synthesized. This 3D graphene material shows enhanced sheet interactions while the cross-linking takes place. With proper solvent stimulation, the integrated 3D graphene material can disassemble as isolated sheets. The driving force for the 3D structure assembly or disassembly is considered to be the forming or breaking of the multiple hydrogen bonding pairs. Furthermore, the 3D material is used as an intelligent dye adsorber to adsorb methylene blue and release it. The controllable and reversible characteristic of this 3D graphene material may open an avenue to the synthesis and application of novel intelligent materials. PMID- 27378189 TI - Global changes of the RNA-bound proteome during the maternal-to-zygotic transition in Drosophila. AB - The maternal-to-zygotic transition (MZT) is a process that occurs in animal embryos at the earliest developmental stages, during which maternally deposited mRNAs and other molecules are degraded and replaced by products of the zygotic genome. The zygotic genome is not activated immediately upon fertilization, and in the pre-MZT embryo post-transcriptional control by RNA-binding proteins (RBPs) orchestrates the first steps of development. To identify relevant Drosophila RBPs organism-wide, we refined the RNA interactome capture method for comparative analysis of the pre- and post-MZT embryos. We determine 523 proteins as high confidence RBPs, half of which were not previously reported to bind RNA. Comparison of the RNA interactomes of pre- and post-MZT embryos reveals high dynamicity of the RNA-bound proteome during early development, and suggests active regulation of RNA binding of some RBPs. This resource provides unprecedented insight into the system of RBPs that govern the earliest steps of Drosophila development. PMID- 27378191 TI - Dynamic reorganization of photosystem II supercomplexes in response to variations in light intensities. AB - Plants are sessile organisms and need to acclimate to ever-changing light conditions in order to survive. These changes trigger a dynamic reorganization of the membrane protein complexes in the thylakoid membranes. Photosystem II (PSII) and its light harvesting system (LHCII) are the major target of this acclimation response, and accumulating evidences indicate that the amount and composition of PSII-LHCII supercomplexes in thylakoids are dynamically adjusted in response to changes in light intensity and quality. In this study, we characterized the PSII LHCII supercomplexes in thylakoid membranes of pea plants in response to long term acclimation to different light intensities. We provide evidence of a reorganization of the PSII-LHCII supercomplexes showing distinct changes in their antenna moiety. Mass spectrometry analysis revealed a specific reduction of Lhcb3, Lhcb6 and M-LHCII trimers bound to the PSII cores, while the Lhcb4.3 isoform increased in response to high light intensities. The modulation of Lhcb protein content correlates with the reduction of the functional PSII antenna size. These results suggest that the Lhcb3, Lhcb4.3 and Lhcb6 antenna subunits are major players in modulation of the PSII antenna size upon long-term acclimation to increased light levels. PsbS was not detected in the isolated PSII LHCII supercomplexes at any light condition, despite an increased accumulation in thylakoids of high light acclimated plants, suggesting that PsbS is not a constitutive component of PSII-LHCII supercomplexes. PMID- 27378192 TI - Sleep quality in patients with chronic illness. AB - AIMS AND OBJECTIVES: To explore sleep quality in patients with chronic illness in primary care. BACKGROUND: Many people suffer from chronic illness with the numbers increasing. One common issue arises from problems that people have with their quality of sleep: a largely under-researched topic. This study exploring poor quality sleep allowed patients to describe their daily struggles with poor sleep in their own lives. This allowed the development of a deeper understanding of what it means to sleep poorly and find out how participants cope with not sleeping well. DESIGN: A qualitative approach enabling a deep exploration of patient's experiences of sleep quality was used. Interviews were conducted with a purposive sample of nine participants from a primary care clinic. Analysis utilised an interpretative approach. RESULTS: Data analysed produced four recurrent themes that were grouped into two categories. First, themes that identified the recognition by participants that 'something was wrong' were abrupt beginning and impact on their life. Second, themes that identified that the participants considered there was 'nothing wrong' were I am fine and I just carry on. CONCLUSION: Data revealed that poor quality sleep can have a profound effect on quality of life. Participants lived without good quality sleep for years. They had come to accept two seemingly irreconcilable ideas that not being able to sleep is an enduring problem with a distinct starting point, and paradoxically, this is not a problem that deserves much professional attention. RELEVANCE TO CLINICAL PRACTICE: Important original data were generated on the impact of poor quality sleep indicating that chronically disturbed sleep can increase the disease burden on patients with chronic illness. The results of this study suggest healthcare professionals need to understand how sleep quality issues impact on patient's experience of chronic illness. Data from this study will help nurses and other health professionals to deepen their understanding of the profound impact of poor quality sleep on patients with chronic illness. A programme of education highlighting the important role of sleep quality in chronic illness is suggested by the issues raised in this study. Nurses are ideally placed to assess sleep quality in patients and tailor intervention to positively affect the quality of life for this group. PMID- 27378193 TI - Recommendations for the diagnosis and initial evaluation of patients with Waldenstrom Macroglobulinaemia: A Task Force from the 8th International Workshop on Waldenstrom Macroglobulinaemia. AB - The diagnosis of Waldenstrom macroglobulinaemia (WM) can be challenging given the variety of signs and symptoms patients can present. Furthermore, once the diagnosis of WM is established, the initial evaluation should be thorough as well as appropriately directed. During the 8th International Workshop for WM in London, United Kingdom, a multi-institutional task force was formed to develop consensus recommendations for the diagnosis and initial evaluation of patients with WM. In this document, we present the results of the deliberations that took place to address these issues. We provide recommendations for history-taking and physical examination, laboratory studies, bone marrow aspiration and biopsy analysis and imaging studies. We also provide guidance on the initial evaluation of special situations, such as anaemia, hyperviscosity, neuropathy, Bing-Neel syndrome and amyloidosis. We hope these recommendations serve as a practical guidance to clinicians taking care of patients with a suspected or an established diagnosis of WM. PMID- 27378194 TI - Metformin use and gynecological cancers: A novel treatment option emerging from drug repositioning. AB - Metformin exerts antitumor effects mainly through AMP-activated protein kinase [AMPK] activation and phosphatidylinositol 3-kinase [PI3K]-Akt-mammalian target of rapamycin [mTOR] inhibition. This drug leads to activation of the cellular energy-sensing liver kinase B1 [LKB1]/AMPK pathway. LKB1 is implicated as a tumor suppressor gene in molecular pathogenesis of different malignancies. AMPK is a serine/threonine protein kinase that acts as an ultra-sensitive cellular energy sensor maintaining the energy balance within the cell. AMPK activation inhibits mRNA translation and proliferation in cancer cells via down-regulation of PI3K/Akt/mTOR pathway. Moreover, metformin decreases the production of insulin, insulin-like growth factor, inflammatory cytokines and vascular endothelial growth factor, and therefore it exerts anti-mitotic, anti-inflammatory and anti angiogenetic effects. Recent in vitro and experimental data suggest that metformin electively targets cancer stem cells, and acts together with chemotherapy to block tumor growth in different cancers. Several epidemiological studies and meta-analysis have shown that metformin use is associated with decreased cancer risk and/or reduced cancer mortality for different malignancies. The present review analyzes the recent biological and clinical data suggesting a possible growth-static effect of metformin also in gynecological cancers. The large majority of available clinical data on the anti-cancer potential of metformin are based on observational studies. Therefore long-term phase II-III clinical trials are strongly warranted to further investigate metformin activity in gynecological cancers. PMID- 27378195 TI - Fully automated synthesis of [(18) F]fluoro-dihydrotestosterone ([(18) F]FDHT) using the FlexLab module. AB - Imaging of androgen receptor expression in prostate cancer using F-18 FDHT is becoming increasingly popular. With the radiolabelling precursor now commercially available, developing a fully automated synthesis of [(18) F] FDHT is important. We have fully automated the synthesis of F-18 FDHT using the iPhase FlexLab module using only commercially available components. Total synthesis time was 90 min, radiochemical yields were 25-33% (n = 11). Radiochemical purity of the final formulation was > 99% and specific activity was > 18.5 GBq/umol for all batches. This method can be up-scaled as desired, thus making it possible to study multiple patients in a day. Furthermore, our procedure uses 4 mg of precursor only and is therefore cost-effective. The synthesis has now been validated at Austin Health and is currently used for [(18) F]FDHT studies in patients. We believe that this method can easily adapted by other modules to further widen the availability of [(18) F]FDHT. PMID- 27378196 TI - Albuminuria in Childhood is a Risk Factor for Chronic Kidney Disease and End Stage Renal Disease. PMID- 27378197 TI - Walking for recreation and transport by geographic remoteness in South Australian adults. AB - OBJECTIVE: To determine differences in walking for recreation and transport between Accessibility/Remoteness Index of Australia (ARIA) categories, in South Australian adults. DESIGN: Cross-sectional self-reported data from adult telephone survey respondents between April and May in 2012 and 2013. SETTING: Population of South Australia. PARTICIPANTS: A total of 4004 adults (aged over 18 years) participated: n = 1956 men and n = 2048 women. Area of residence was categorised using ARIA (major city, inner regional, outer regional and remote/very remote). MAIN OUTCOME MEASURE(S): Self-reported participation in walking for transport and recreation/exercise as the number of times and minutes per week. Data were analysed using Kruskal-Wallis test for median minutes and negative binomial regression for times walked with adjustment for socioeconomic status, age and body mass index. RESULTS: Average age was 47.8 +/- 18.5 years, 51.1% were women, 70.9% lived in the major cities, 14.6% in inner regional, 10.8% in outer regional and 3.6% in remote/very remote areas. Relative to major city, times walked for recreation was lower for only remote/very remote residents (incidence rate ratio (IRR) 0.74 (95%CI 0.59-0.92), P = 0.008). This difference was only observed for men (IRR 0.54 (95%CI 0.39-0.73), P < 0.001). Relative to major city, times walked for transport was less for inner regional (IRR 0.74 (95%CI 0.67-0.85), P < 0.001) and outer regional (IRR 0.64 (95%CI 0.56-0.74), P < 0.001) only. This difference in transport walking was seen in both men and women. CONCLUSION: Frequency of walking varied by purpose, level of remoteness and sex. As walking is the focus of population-level health promotion, more detailed understanding of the aetiology of regular walking is needed. PMID- 27378198 TI - Efficient transmission of IncFIIY and IncL plasmids and Klebsiella pneumoniae ST101 clone producing OXA-48, NDM-1 or OXA-181 in Bucharest hospitals. PMID- 27378199 TI - Improved Blood Pressure Control to Reduce Cardiovascular Disease Morbidity and Mortality: The Standardized Hypertension Treatment and Prevention Project. AB - Hypertension is the leading remediable risk factor for cardiovascular disease, affecting more than 1 billion people worldwide, and is responsible for more than 10 million preventable deaths globally each year. While hypertension can be successfully diagnosed and treated, only one in seven persons with hypertension have controlled blood pressure. To meet the challenge of improving the control of hypertension, particularly in low- and middle-income countries, the authors developed the Standardized Hypertension Treatment and Prevention Project, which involves a health systems-strengthening approach that advocates for standardized hypertension management using evidence-based interventions. These interventions include the use of standardized treatment protocols, a core set of medications along with improved procurement mechanisms to increase the availability and affordability of these medications, registries for cohort monitoring and evaluation, patient empowerment, team-based care (task shifting), and community engagement. With political will and strong partnerships, this approach provides the groundwork to reduce high blood pressure and cardiovascular disease-related morbidity and mortality. PMID- 27378200 TI - Associations between liking for fat, sweet or salt and obesity risk in French adults: a prospective cohort study. AB - BACKGROUND: Individual sensory liking appears to be an important determinant of dietary intake and may consequently influence weight status. Cross-sectional studies have shown positive association between fat liking and weight status and equivocal results regarding salt and sweet liking. Moreover, the contribution of dietary intake to explain this relationship has not been studied yet. We investigated the prospective association between sensory liking for fat, sweet or salt and the onset of obesity over 5 years in adults, and the mediating effect of dietary intake. METHODS: We prospectively examine the risk of obesity among 24,776 French adults participating in the NutriNet-Sante cohort study. Liking scores and dietary data were assessed at baseline using a validated web-based questionnaire and 24 h records, respectively. Self-reported anthropometric data were collected using web-based questionnaire, each year during 5 years. Associations between quartiles of liking for fat, sweet or salt and obesity risk, and the mediating effect of diet were assessed by multivariate Cox proportional hazards models stratified by gender, adjusted for sociodemographic and lifestyle factors. RESULTS: In both genders, sensory liking for fat was associated with an increased risk of obesity (hazard ratios for quartile 4 compared to quartile 1, men: HR(Q4vs.Q1) = 2.39 (95% CI 1.39,4.11) P-trend = 0.0005, women: HR(Q4vs.Q1) = 2.02 (1.51,2.71) P-trend = <0.0001). Dietary intake explained 32% in men and 52% in women of the overall variation of liking for fat in obesity. Sensory liking for sweet was associated with a decreased risk of obesity (men: HR(Q4vs.Q1) = 0.51 (0.31,0.83) P-trend = 0.01, women: HR(Q4vs.Q1) = 0.72 (0.54,0.96) P-trend = 0.035). No significant association between salt liking and the risk of obesity was found. CONCLUSIONS: Unlike sweet and salt liking, higher liking for fat appears to be a major risk factor of obesity, largely explained by dietary intake. Our findings emphasize the need to centrally position sensory liking in obesity prevention. PMID- 27378201 TI - The effects of direct hemoperfusion using a polymyxin B-immobilized column in a pig model of severe Pseudomonas aeruginosa pneumonia. AB - BACKGROUND: Hemoperfusion through a column containing polymyxin B-immobilized fiber (PMX-HP) is beneficial in abdominal sepsis. We assessed the effects of PMX HP in a model of severe Pseudomonas aeruginosa pneumonia. METHODS: Eighteen pigs with severe P. aeruginosa pneumonia were mechanically ventilated for 76 h. Pigs were randomized to receive standard treatment with fluids and vasoactive drugs, or standard treatment with two 3-h PMX-HP sessions. Antibiotics against P. aeruginosa were never administered. We assessed endotoxemia through the endotoxin activity assay (EA). We measured the static lung elastance, ratio of arterial partial pressure per inspiratory fraction of oxygen (PaO2/FIO2), mean arterial pressure, cardiac output, systemic vascular resistance and inotropic score. Finally, every 24 h, we assessed complete blood count. RESULTS: In comparison with the control group, PMX-HP decreased percentage of circulating neutrophils from 47.4 +/- 13.8 to 40.8 +/- 11.5 % (p = 0.009). In a subgroup of animals with the worst hemodynamic impairment, EA in the control and PMX-HP groups was 0.50 +/ 0.29 and 0.29 +/- 0.14, respectively (p = 0.018). Additionally, in the control and PMX-HP groups, static lung elastance was 26.9 +/- 8.7 and 25.3 +/- 7.5 cm H2O/L (p = 0.558), PaO2/FIO2 was 347.3 +/- 61.9 and 356.4 +/- 84.0 mmHg (p = 0.118), mean arterial pressure was 81.2 +/- 10.3 and 81.6 +/- 13.1 mmHg (p = 0.960), cardiac output was 3.30 +/- 1.11 and 3.28 +/- 1.19 L/min (p = 0.535), systemic vascular resistance was 1982.6 +/- 608.4 and 2011.8 +/- 750.0 dyne/s/cm( 5) (p = 0.939), and inotropic score was 0.25 +/- 0.10 and 0.26 +/- 0.18 (p = 0.864). CONCLUSIONS: In mechanically ventilated pigs with severe P. aeruginosa pneumonia, PMX-HP does not have any valuable clinical benefit, and studies are warranted to fully evaluate a potential role of PMX-HP in septic shock associated with severe pulmonary infections. PMID- 27378202 TI - A putative mitochondrial calcium uniporter in A. fumigatus contributes to mitochondrial Ca(2+) homeostasis and stress responses. AB - Ca(2+) uptake into mitochondria plays a central role in cell physiology by stimulating ATP production, shaping cytosolic Ca(2+) transients and regulating cell survival or death. Although this system has been studied extensively in mammalian cells, the physiological implications of Ca(2+) uptake into mitochondria in fungal cells are still unknown. In this study, a bi-directional best-hit BLASTP search revealed that the genome of Aspergillus fumigatus encodes a homolog of a putative mitochondrial Ca(2+) uniporter (MCU) and a mitochondrial carrier protein AGC1/MICU1 homolog. Both putative homologs are mitochondrially localized and required for the response to azole and oxidative stress such that the loss of either McuA or AgcA results in reduced susceptibility to azole and oxidative stress, suggesting a role in environmental stress adaptation. Overexpressing mcuA restores the azole-resistance phenotype of the DeltaagcA strain to wild-type levels, but not vice versa, indicating McuA plays a dominant role during these stress responses. Using a mitochondrially targeted version of the calcium-sensitive photoprotein aequorin, we found that only mcuA deletion leads to dysfunctional [Ca(2+)]mt and [Ca(2+)]c homeostasis, suggesting that McuA, but not AgcA, contributes to Ca(2+) uptake into mitochondria. Further point mutation experiments combined with extracellular Ca(2+) chelator treatment verified that two predicted Ca(2+)-binding sites in McuA are required for Ca(2+) uptake into mitochondria and stress responses through the regulation of [Ca(2+)]c homeostasis. PMID- 27378203 TI - Metabolic activity in dormant conidia of Aspergillus niger and developmental changes during conidial outgrowth. AB - The early stages of development of Aspergillus niger conidia during outgrowth were explored by combining genome-wide gene expression analysis (RNAseq), proteomics, Warburg manometry and uptake studies. Resting conidia suspended in water were demonstrated for the first time to be metabolically active as low levels of oxygen uptake and the generation of carbon dioxide were detected, suggesting that low-level respiratory metabolism occurs in conidia for maintenance. Upon triggering of spore germination, generation of CO2 increased dramatically. For a short period, which coincided with mobilisation of the intracellular polyol, trehalose, there was no increase in uptake of O2 indicating that trehalose was metabolised by fermentation. Data from genome-wide mRNA profiling showed the presence of transcripts associated with fermentative and respiratory metabolism in resting conidia. Following triggering of conidial outgrowth, there was a clear switch to respiration after 25min, confirmed by cyanide inhibition. No effect of SHAM, salicylhydroxamic acid, on respiration suggests electron flow via cytochrome c oxidase. Glucose entry into spores was not detectable before 1h after triggering germination. The impact of sorbic acid on germination was examined and we showed that it inhibits glucose uptake. O2 uptake was also inhibited, delaying the onset of respiration and extending the period of fermentation. In conclusion, we show that conidia suspended in water are not completely dormant and that conidial outgrowth involves fermentative metabolism that precedes respiration. PMID- 27378204 TI - Ligand-targeted bacterial minicells: Futuristic nano-sized drug delivery system for the efficient and cost effective delivery of shRNA to cancer cells. AB - In this study, shRNA against VEGFA was packaged in bacterial minicells and surface of minicells was modified with folic acid. Analysis of cellular internalization revealed that folic acid conjugated minicells internalized through receptor mediated endocytosis in folate and PSMA receptor positive KB and LNCaP cells, respectively. In contrast, A549 (folate receptor negative) cells showed minute internalization. In vitro delivery of FAminicellsVEGFA significantly reduced the expression of VEGFA mRNA in KB and LNCaP cells whereas expression of VEGFA remained unaltered in A549 cells. FAminicellsVEGFA significantly reduced tumor volume in mice bearing KB and LNCaP xenograft. On contrary, gradual increase in the tumor volume was recorded in A549 xenograft. FAminicellsVEGFA significantly silenced the VEGFA mRNA in KB and LNCaP xenograft. Expression of VEGFA remained same in FAminicellsVEGFA delivered A549 xenograft. In vivo biodistribution study showed that majority of FAminicellsVEGFA were localized in the tumor followed by intravenous administration. PMID- 27378205 TI - Heparin-appended polycaprolactone core/corona nanoparticles for site specific delivery of 5-fluorouracil. AB - The aim of the present work is to formulate heparin-modified-polycaprolactone (HEP) core shell nanoparticles (NPs) of 5-fluorouracil (5-FU). These NPs were characterized for various in vitro parameters like particle size, zeta potential, etc. HEP NPs were found to maintain comparatively slower drug release pattern (98.9% in 96 h) than PCL NPs. Cytotoxicity studies demonstrated a massive cytotoxic potential of 5-FU-loaded HEP NPs in A549, MDA-MD-435, and SK-OV-3 cancer cell lines. Pharmacokinetic parameters were also determined in blood after IV administration of HEP NPs: AUC, Cmax, MRT, and Tmax values are 6096.075 +/- 5.90 MUg h/mL, 144.38 +/- 1.52 MUg/L, 58.71 +/- 0.25 h, 96 +/- 0.50 h, respectively and 117.92 +/- 1.78, 45.35 +/- 3.00, 1.2 +/- 0.25, 0.5 +/- 0.02 in plain 5-FU solution. PMID- 27378207 TI - Arterioveneuze Aneurysmata Van De Long. AB - A case history is presented of a 12 year old girl with pulmonary arteriovenous fistula. The diagnosis was based on clinical and radiological signs and on physiological evidence for a large arteriovenous shunting of blood in the lungs. As an unexpected other finding, diffusing capacity was markedly decreased. The largest radiologically apparent fistula, situated in the right lower lobe, was resected; peroperative clamping of pulmonary arterial blood supply to the affected lobe substantiated the presence of an arteriovenous fistula. Following surgery, arteriovenous shunting was found to be only slightly decreased (from 30 % to 25 % of cardiac output). In the resected lobe cavernous angiomata were demonstrated but also multiple capillary teleangiectases and marked thickening of alveolar walls. We suggest that the finding of a decreased diffuing capacity in patients with arteriovenous fistula indicates diffuse pulmonary disease which precludes surgical correction. A review of recent literature on pulmonary arteriovenous fistula is presented. PMID- 27378206 TI - Zinc acetate lozenges for treating the common cold: an individual patient data meta-analysis. AB - AIMS: The aim of this study was to determine whether the allergy status and other characteristics of common cold patients modify the effects of zinc acetate lozenges. METHODS: We had available individual patient data for three randomized placebo-controlled trials in which zinc acetate lozenges were administered to common cold patients. We used both one stage and two stage meta-analysis to estimate the effects of zinc lozenges. RESULTS: The total number of common cold patients was 199, the majority being females. Eighty percent of them fell into the age range 20-50 years. One third of the patients had allergies. The one stage meta-analysis gave an overall estimate of 2.73 days (95% CI 1.8, 3.3 days) shorter colds by zinc acetate lozenge usage. The two stage meta-analysis gave an estimate of 2.94 days (95% CI 2.1, 3.8 days) reduction in common cold duration. These estimates are to be compared with the 7 day average duration of colds in the three trials. The effect of zinc lozenges was not modified by allergy status, smoking, baseline severity of the common cold, age, gender or ethnic group. CONCLUSION: Since the effects of zinc acetate lozenges were consistent between the compared subgroups, the overall estimates for effect seemed applicable over a wide range of common cold patients. While the optimal composition of zinc lozenges and the best frequency of their administration should be further investigated, given the current evidence of efficacy, common cold patients may be encouraged to try zinc lozenges for treating their colds. PMID- 27378209 TI - Postsynthetic Inner-Surface Functionalization of the Highly Stable Zirconium Based Metal-Organic Framework DUT-67. AB - A postsynthetic functionalization approach was used to tailor the hydrophobicity of DUT-67, a metal-organic framework (MOF) consisting of 8-connected Zr6O6(OH)2 clusters and 2,5-thiophenedicarboxylate as the ligand, using postsynthetic exchange of the modulator by fluorinated monocarboxylates. Water adsorption isotherms demonstrated that, by the incorporation of such hydrophobic molecules, the hydrophobicity of the inner surface of the network can be tuned. Furthermore, tolerance of the material toward the removal of adsorbed water can be significantly enhanced compared to the parent DUT-67 MOF. PMID- 27378210 TI - Sticking to (first) principles: quantum molecular dynamics and Bayesian probabilistic methods to simulate aquatic pollutant absorption spectra. AB - This work explores the relationship between theoretically predicted excitation energies and experimental molar absorption spectra as they pertain to environmental aquatic photochemistry. An overview of pertinent Quantum Chemical descriptions of sunlight-driven electronic transitions in organic pollutants is presented. Second, a combined molecular dynamics (MD), time-dependent density functional theory (TD-DFT) analysis of the ultraviolet to visible (UV-Vis) absorption spectra of six model organic compounds is presented alongside accurate experimental data. The functional relationship between the experimentally observed molar absorption spectrum and the discrete quantum transitions is examined. A rigorous comparison of the accuracy of the theoretical transition energies (DeltaES0->Sn) and oscillator strength (fS0->Sn) is afforded by the probabilistic convolution and deconvolution procedure described. This method of deconvolution of experimental spectra using a Gaussian Mixture Model combined with Bayesian Information Criteria (BIC) to determine the mean (MU) and standard deviation (sigma) as well as the number of observed singlet to singlet transition energy state distributions. This procedure allows a direct comparison of the one electron (quantum) transitions that are the result of quantum chemical calculations and the ensemble of non-adiabatic quantum states that produce the macroscopic effect of a molar absorption spectrum. Poor agreement between the vertical excitation energies produced from TD-DFT calculations with five different functionals (CAM-B3LYP, PBE0, M06-2X, BP86, and LC-BLYP) suggest a failure of the theory to capture the low energy, environmentally important, electronic transitions in our model organic pollutants. However, the method of explicit-solvation of the organic solute using the quantum Effective Fragment Potential (EFP) in a density functional molecular dynamics trajectory simulation shows promise as a robust model of the hydrated organic pollutant. Furthermore, the described protocol can be extended using higher-level equilibration and vertical excitation methods to increase the numerical accuracy and describe multi reference electronic transitions. Finally, a measure of the accuracy of theoretically derived absorption spectra is discussed as a tool to further develop our capacity to produce accurate a priori simulations of sunlight-driven photochemistry in natural waters. PMID- 27378211 TI - Commentary: Cerebral Lateralization is Protective in the Very Prematurely Born. PMID- 27378212 TI - Radiotherapy for diffuse brainstem glioma in children and young adults. AB - BACKGROUND: Diffuse brainstem glioma is a devastating disease with very poor prognosis. The most commonly used radiological treatment is conventional fractionated radiation. So far, there is no meta-analysis or systematic review available that assesses the benefits or harms of radiation in people with diffuse brainstem glioma. OBJECTIVES: To assess the effects of conventional fractionated radiotherapy (with or without chemotherapy) versus other therapies (including different radiotherapy techniques) for newly diagnosed diffuse brainstem gliomas in children and young adults aged 0 to 21 years. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE/PubMed, and EMBASE to 19 August 2015. We scanned conference proceedings from the International Society for Paediatric Oncology (SIOP), International Symposium on Paediatric Neuro-Oncology (ISPNO), Society of Neuro-Oncology (SNO), and European Association of Neuro-Oncology (EANO) from 1 January 2010 to 19 August 2015. We searched trial registers including the International Standard Randomised Controlled Trial Number (ISRCTN) Register, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and the register of the National Institutes of Health to 19 August 2015. We imposed no language restrictions. SELECTION CRITERIA: All randomised controlled trials (RCTs), quasi randomised trials (QRCTs), or controlled clinical trials (CCTs) that compared conventional fractionated radiotherapy (with or without chemotherapy) versus other therapies (including different radiotherapy techniques) for newly diagnosed diffuse brainstem glioma in children and young adults aged 0 to 21 years. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies for inclusion, extracted data, assessed the risk of bias in each eligible trial, and conducted GRADE assessment of included studies. We resolved disagreements through discussion. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: We identified two RCTs that fulfilled our inclusion criteria. The two trials tested different comparisons.One multi-institutional RCT included 130 participants and compared hyperfractionated radiotherapy (six-week course with twice a day treatment of 117 cGy per fraction to a total dose of 7020 cGy) with conventional radiotherapy (six week course with once a day treatment of 180 cGy per fraction to a total dose of 5400 cGy). The median time overall survival (OS) was 8.5 months in the conventional group and 8.0 months in the hyperfractionated group. We detected no clear evidence of effect on OS or event-free survival (EFS) in participants receiving hyperfractionated radiotherapy compared with conventional radiotherapy (OS: hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.75 to 1.53; EFS: HR 1.26, 95% CI 0.83 to 1.90). Radiological response (risk ratio (RR) 0.94, 95% CI 0.54 to 1.63) and various types of toxicities were similar in the two groups. There was no information on other outcomes. According to the GRADE approach, we judged the quality of evidence to be low (i.e. further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate) for OS and EFS, and very low (i.e. we are very uncertain about the estimate) for radiological response and toxicities.The second RCT included 71 participants and compared hypofractionated radiotherapy (39 Gy in 13 fractions over 2.6 weeks, 3 Gy per fraction) with conventional radiotherapy (54 Gy in 30 fractions over six weeks, 1.8 Gy per fraction). This trial reported a median OS of 7.8 months for the hypofractionated group and 9.5 months for the conventional group. It reported a progression-free survival (PFS) of 6.3 months for the hypofractionated group and 7.3 months for the conventional group. We found no clear evidence of effect on OS (HR 1.03, 95% CI 0.53 to 2.01) or PFS (HR 1.19, 95% CI 0.63 to 2.22) in participants receiving hypofractionated radiotherapy when compared with participants receiving conventional radiotherapy. The mainly observed adverse effect was local erythema and dry desquamation especially behind the auricles. There were some other toxicities, but there was no statistically significant difference between treatment groups. There was no information on other outcomes. We judged the quality of evidence to be moderate (i.e. further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate) for OS, and low for PFS and toxicities. It should be mentioned that the sample size in this RCT was small, which could lead to insufficient statistical power for a clinically relevant outcome. AUTHORS' CONCLUSIONS: We could make no definitive conclusions from this review based on the currently available evidence. Further research is needed to establish the role of radiotherapy in the management of newly diagnosed diffuse brainstem glioma in children and young adults. Future RCTs should be conducted with adequate power and all relevant outcomes should be taken into consideration. Moreover, international multicentre collaboration is encouraged. Considering the potential advantage of hypofractionated radiotherapy to decrease the treatment burden and increase the quality of remaining life, we suggest that more attention should be paid to hypofractionated radiotherapy. PMID- 27378213 TI - Extremely Robust and Patternable Electrodes for Copy-Paper-Based Electronics. AB - We propose a fabrication process for extremely robust and easily patternable silver nanowire (AgNW) electrodes on paper. Using an auxiliary donor layer and a simple laminating process, AgNWs can be easily transferred to copy paper as well as various other substrates using a dry process. Intercalating a polymeric binder between the AgNWs and the substrate through a simple printing technique enhances adhesion, not only guaranteeing high foldability of the electrodes, but also facilitating selective patterning of the AgNWs. Using the proposed process, extremely crease-tolerant electronics based on copy paper can be fabricated, such as a printed circuit board for a 7-segment display, portable heater, and capacitive touch sensor, demonstrating the applicability of the AgNWs-based electrodes to paper electronics. PMID- 27378214 TI - Pharmaceuticals, Their Metabolites, and Other Polar Pollutants in Field-Grown Vegetables Irrigated with Treated Municipal Wastewater. AB - The reuse of treated municipal wastewater for crop irrigation is a necessity in arid and semiarid regions but a potential entrance for emerging contaminants into the food chain. However, little attention has yet been paid to the detection of micropollutants and possible metabolites in vegetables grown under realistic field conditions. In this study, the uptake of 28 micropollutants and carbamazepine metabolites in 10 different field-grown vegetable species (among them carrot, lettuce, potato, and zucchini) from Jordan was studied. A total of 12 micropollutants and six carbamazepine metabolites, four of which have never been analyzed before in plant-uptake studies, could be detected in all of the samples in concentrations ranging from 1.7 to 216 ng per g of dry weight. In edible tissues, the total concentration of micropollutants decreased in the order of leafy (247-533) > root (73-126) > fruit-bearing (5-76 ng per g of dry weight) vegetables. A preliminary health-risk assessment for nine compounds according to the TTC concept shows no risk for seven of the micropollutats; for ciprofloxacin and 10,11-epoxycarbamazepine, however, more-specific toxicity data would be required for a refined risk assessment. PMID- 27378215 TI - A Multistate Molecular Switch Based on the 6,8-Rearrangement in Bromo apigeninidin Operated with pH and Host-Guest Inputs. AB - The equilibrium between 6- and 8-bromo-apigeninidin is quantitatively displaced toward the formation of the former in the presence of cucurbit[7]uril because of the selective recognition of the 6-bromo isomer by the host. This phenomenon permits us to conceive a unidirectional multistate switch addressed with host guest inputs and enables the reversible activation and deactivation of the 6-/8 bromo-apigeninidin dynamic molecular multistate through coupled host-guest and pH inputs. PMID- 27378216 TI - Plasma and tissue disposition of florfenicol in Escherichia coli lipopolysaccharide-induced endotoxaemic sheep. AB - 1. The purpose of this study was to understand the effects of the acute inflammatory response (AIR) induced by Escherichia coli lipopolysaccharide (LPS) on florfenicol (FFC) and FFC-amine (FFC-a) plasma and tissue concentrations. 2. Ten Suffolk Down sheep, 60.5 +/- 4.7 kg, were distributed into two experimental groups: group 1 (LPS) treated with three intravenous doses of 1 MUg/kg bw of LPS at 24, 16, and 0.75 h (45 min) before FFC treatment; group 2 (Control) was treated with saline solution (SS) in parallel to group 1. An IM dose of 20 mg FFC/kg was administered at 0.75 h after the last injection of LPS or SS. Blood and tissue samples were taken after FFC administration. 3. The plasma AUC0-4 h values of FFC were higher (p = 0.0313) in sheep treated with LPS (21.8 +/- 2.0 MUg.min/mL) compared with the control group (12.8 +/- 2.3 MUg.min/mL). Lipopolysaccharide injections increased FFC concentrations in kidneys, spleen, and brain. Low levels of plasma FFC-a were observed in control sheep (Cmax = 0.14 +/- 0.01 MUg/mL) with a metabolite ratio (MR) of 4.0 +/- 0.87%. While in the LPS group, Cmax increased slightly (0.25 +/- 0.01 MUg/mL), and MR decreased to 2.8 +/ 0.17%. 4. The changes observed in the plasma and tissue concentrations of FFC were attributed to the pathophysiological effects of LPS on renal hemodynamics that modified tissue distribution and reduced elimination of the drug. PMID- 27378217 TI - Chylous ascites after lymphadenectomy for gynecological malignancies. AB - BACKGROUND AND OBJECTIVES: Chylous ascites, an accumulation of milky-white lymph fluid in the peritoneal cavity, is a rare complication following retroperitoneal lymphadenectomy. This study evaluated the appearance and management of chylous ascites following lymphadenectomy for gynecological malignancies. METHODS: A total of 931 patients who underwent lymphadenectomy for gynecological malignancies at Erlangen University Hospital between 2002 and 2013 were reviewed retrospectively. RESULTS: Chylous ascites occurred postoperatively in 28 of the 931 patients (3.0%). All patients with chylous ascites had undergone combined systematic para-aortic and pelvic lymphadenectomy (SAPL). Patients with chylous ascites had a larger mean number of lymph nodes removed (51.9 vs. 40.0, P = 0.002) and the proportion of laparoscopic SAPLs was significantly higher (20/28; 71.4%) in comparison with open surgery (8/28; 28.6%) (P < 0.0001). Additional parameters, such as the number of positive lymph nodes, were not significantly associated with the occurrence of chylous ascites. Conservative management was sufficient to resolve chylous ascites in all observed cases, with a mean time to resolution of 8 days. CONCLUSIONS: Postoperative chylous ascites was more frequently observed in patients with laparoscopic SAPL in comparison with open SAPL and was strongly associated with a larger mean number of removed lymph nodes. J. Surg. Oncol. 2016;114:613-618. (c) 2016 Wiley Periodicals, Inc. PMID- 27378218 TI - Facile modulation of optical properties of octagold clusters through the control of ligand-mediated interactions. AB - In the recent development of structurally defined ligand-stabilized gold clusters, it has been revealed that not only the inorganic units but also the surrounding organic ligands substantially affect their electronic/optical properties. In this work, a series of core + exo type Au8 clusters decorated by dppp (Ph2P(CH2)3PPh2) and arylthiolate ligands ([Au8(dppp)4(SR)2](2+), 1-5) were synthesized, and their optical properties were studied in order to gain insights into the perturbation effects of the organic ligands. 1-5 showed visible absorption and photoluminescence emission bands at longer wavelengths compared to their chloro- and acetylide-modified analogues, suggesting the contribution of weak non-bonding interactions of the Au framework with the ligand heteroatoms. Upon acid treatment, 2- and 4-pyridinethiolate clusters (R = Py, 2 and 4) showed larger red shifts of the absorption and emission bands than the 3-pyridyl isomer (3), implying the involvement of the resonance structures of the SPy units. On the other hand, all regioisomers (2-4) showed large photoluminescence enhancements upon pyridine protonation. X-ray crystallographic and NMR analyses of 4 and its protonated form (4') showed that the electron-deficient pyridinium rings of 4' form pi-stacks with neighbouring phenyl groups of dppp, suggesting that the orientation of the surface aromatics is a plausible factor governing the emission efficiency. These observations provide examples of successful modulation of optical properties of small gold clusters through the electronic and/or steric perturbation by the proximal organic ligands, highlighting the importance of the ligand design in the fine tuning of cluster properties directed for optical chemosensors and luminescent materials. PMID- 27378219 TI - Dietary unsaponifiable fraction of extra virgin olive oil supplementation attenuates lung injury and DNA damage of rats co-exposed to aluminum and acrylamide. AB - Aluminum chloride (AlCl3) and acrylamide (ACR) are well known as environmental pollutants inducing oxidative stress. Our study investigated the effects of these contaminants and if the hydrophilic fraction of extra virgin olive oil was able to prevent lung oxidative stress and DNA damage. Animals were divided into four groups of six each: group 1, serving as controls, received distilled water; group 2 received in drinking water aluminum chloride (50 mg/ kg body weight) and by gavage acrylamide (20 mg/kg body weight); group 3 received both aluminum and acrylamide in the same way and the same dose as group 2 and hydrophilic fraction from olive oil (OOHF) (1 ml) by gavage; group 4 received only OOHF by gavage. Exposure of rats to both aluminum and acrylamide provoked oxidative stress in lung tissue based on biochemical parameters and histopathological alterations. In fact, we have observed an increase in malondialdehyde (MDA), H2O2, and advanced oxidation protein product (AOPP) and a decrease in reduced glutathione (GSH), non protein thiols (NPSH), and vitamin C levels. Activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were also decreased. Histopathological changes in lung tissue were noted like emphysema, vascular congestion, and infiltration of inflammatory cells. A random DNA degradation was observed on agarose gel in the lung of AlCl3 and acrylamide (ACR)-treated rats. Co-administration of OOHF to treated rats improved biochemical parameters to near control values and lung histoarchitecture. The smear formation of genomic DNA was reduced. The hydrophilic fraction of extra virgin olive oil might provide a basis for developing a new dietary supplementation strategy in order to prevent lung tissue damage. PMID- 27378221 TI - Addition to Special Issue "Fate and effects of the residues of anticancer drugs in the environment". PMID- 27378220 TI - Determination of organophosphorus pesticides and their major degradation product residues in food samples by HPLC-UV. AB - A simple method based on dispersive solid-phase extraction (DSPE) and dispersive liquid-liquid microextraction method based on solidification of floating organic droplets (DLLME-SFO) was developed for the extraction of chlorpyrifos (CP), chlorpyrifos-methyl (CPM), and their main degradation product 3,5,6-trichloro-2 pyridinol (TCP) in tomato and cucumber samples. The determination was carried out by high performance liquid chromatography with ultraviolet detection (HPLC-UV). In the DSPE-DLLME-SFO, the analytes were first extracted with acetone. The clean up of the extract by DSPE was carried out by directly adding activated carbon sorbent into the extract solution, followed by shaking and filtration. Under the optimum conditions, the proposed method was sensitive and showed a good linearity within a range of 2-500 ng/g, with the correlation coefficients (r) varying from 0.9991 to 0.9996. The enrichment factors ranged from 127 to 138. The limit of detections (LODs) were in the range of 0.12-0.68 ng/g, and the relative standard deviations (RSDs) for 50 ng/g of each analytes in tomato samples were in the range of 3.25-6.26 % (n = 5). The proposed method was successfully applied for the extraction and determination of the mentioned analytes residues in tomato and cucumber samples, and satisfactory results were obtained. PMID- 27378222 TI - Modeling urban air pollution with optimized hierarchical fuzzy inference system. AB - Environmental exposure assessments (EEA) and epidemiological studies require urban air pollution models with appropriate spatial and temporal resolutions. Uncertain available data and inflexible models can limit air pollution modeling techniques, particularly in under developing countries. This paper develops a hierarchical fuzzy inference system (HFIS) to model air pollution under different land use, transportation, and meteorological conditions. To improve performance, the system treats the issue as a large-scale and high-dimensional problem and develops the proposed model using a three-step approach. In the first step, a geospatial information system (GIS) and probabilistic methods are used to preprocess the data. In the second step, a hierarchical structure is generated based on the problem. In the third step, the accuracy and complexity of the model are simultaneously optimized with a multiple objective particle swarm optimization (MOPSO) algorithm. We examine the capabilities of the proposed model for predicting daily and annual mean PM2.5 and NO2 and compare the accuracy of the results with representative models from existing literature. The benefits provided by the model features, including probabilistic preprocessing, multi objective optimization, and hierarchical structure, are precisely evaluated by comparing five different consecutive models in terms of accuracy and complexity criteria. Fivefold cross validation is used to assess the performance of the generated models. The respective average RMSEs and coefficients of determination (R (2)) for the test datasets using proposed model are as follows: daily PM2.5 = (8.13, 0.78), annual mean PM2.5 = (4.96, 0.80), daily NO2 = (5.63, 0.79), and annual mean NO2 = (2.89, 0.83). The obtained results demonstrate that the developed hierarchical fuzzy inference system can be utilized for modeling air pollution in EEA and epidemiological studies. PMID- 27378223 TI - Theoretical study and control optimization of an integrated pest management predator-prey model with power growth rate. AB - This work presents a pest control predator-prey model, where rate of change in prey density follows a scaling law with exponent less than one and the control is by an integrated management strategy. The aim is to investigate the change in system dynamics and determine a pest control level with minimum control price. First, the dynamics of the proposed model without control is investigated by taking the exponent as an index parameter. And then, to determine the frequency of spraying chemical pesticide and yield releases of the predator, the existence of the order-1 periodic orbit of the control system is discussed in cases. Furthermore, to ensure a certain robustness of the adopted control, i.e., for an inaccurately detected species density or a deviation, the control system could be stabilized at the order-1 periodic orbit, the stability of the order-1 periodic orbit is verified by an stability criterion for a general semi-continuous dynamical system. In addition, to minimize the total cost input in pest control, an optimization problem is formulated and the optimum pest control level is obtained. At last, the numerical simulations with a specific model are carried out to complement the theoretical results. PMID- 27378224 TI - Prognostic factors, pathophysiology and novel biomarkers in Crimean-Congo hemorrhagic fever. AB - Crimean-Congo hemorrhagic fever (CCHF) is a geographically widespread tick-borne zoonosis. The clinical spectrum of the illness varies from mild infection to severe disease and death. In severe cases, hemorrhagic manifestations develop, with fatality rates of 4-20%, depending on the geographic region and quality of the health care. Although vast majority of the CCHF cases were reported from Turkey, mortality rate is lower than the other regions, which is 5% on average. Prediction of the clinical course of the disease enables appropriate management planning by the physician and prompt transportation, if needed, of the patient to a tertiary care hospital for an intensive therapy. Thus, predicting the outcome of the disease may avert potential mortality. There are numerous studies investigating the prognostic factors of CCHF in the literature. Majority of them were reported from Turkey and included investigations on clinical and biochemical parameters, severity scoring systems and some novel biomarkers. Somnolence, bleeding, thrombocytopenia, elevated liver enzymes and prolonged bleeding times are the most frequently reported prognostic factors to predict the clinical course of the disease earlier. High viral load seems to be the strongest predictor to make a clinical decision about the patient outcome. The severity scoring systems based on clinically important mortality-related parameters are especially useful for clinicians working in the field to predict the course of the disease and to decide which patient should be referred to a tertiary care hospital for intensive care. In the light of the pathophysiological characteristics of CCHF, some new biomarkers of prognosis including cytokines, soluble adhesion molecules, genetic polymorphisms and coagulopathy parameters were also investigated. However most of these tests are not available to clinicians and they were obtained mostly for research purposes. In spite of the various studies about prognostic factors, they have several inherent limitations, including large variability in the results and confusing data that are not useful for clinicians in routine practice. In this paper, the results of diverse studies of the prediction of the prognosis in CCHF based on epidemiological, clinical and laboratory findings of the disease were summarized and suggestions for future studies are provided. PMID- 27378225 TI - Prevention strategies differentially modulate the impact of cytomegalovirus replication on CD8(+) T-cell differentiation in high-risk solid organ transplant patients. AB - The present study aimed to determine whether antiviral prevention strategies against cytomegalovirus (CMV) infection used in high-risk D+R- solid organ transplanted patients can modulate the impact of CMV replication on CD8(+) T-cell differentiation. The different CD8(+) T-cell subpopulations were measured at a single point when at least one year had elapsed since transplantation. A total of 68 D+R- patients were included, of which 33 underwent pre-emptive therapy and 35 received prophylaxis. Multivariate analysis showed that CMV replication was associated with the expansion of CD28? EMRA CD8(+) T cells in patients managed pre-emptively but not in patients under prophylaxis (21.4% vs. 3.6%). This finding is likely related to the higher frequency of CMV recurrence observed in patients under pre-emptive therapy compared to those under prophylaxis (75% vs. 14.3%; p < 0.001). In fact, multivariate analysis showed that having more than one replication episode was associated with a 17.2% increase (p = 0.001) in the percentage of CD28? EMRA CD8(+) T cells compared to "no episode" and with a 10.9% increase with respect to "single episodes" (p = 0.025). Additionally, patients with IFNgamma response to CMV (QuantiFERON-CMV Reactive) had a higher percentage of late-differentiated CD8(+) T cells than patients lacking this response. In summary, recurrent CMV replication in D+R- patients under pre-emptive therapy was associated with the expansion of CD28? EMRA CD8(+) T cells, which might have a short-term beneficial effect related to the high functionality of this T-cell subpopulation. Nevertheless, we cannot rule out that this accumulation might have a long-term detrimental effect related to immunosenescence and inflammation. PMID- 27378226 TI - The Membrane-Bound Form of IL-17A Promotes the Growth and Tumorigenicity of Colon Cancer Cells. AB - Interleukin-17A is a member of the IL-17 family, and is known as CTLA8 in the mouse. It is produced by T lymphocytes and NK cells and has proinflammatory roles, inducing cytokine and chemokine production. However, its role in tumor biology remains controversial. We investigated the effects of locally produced IL 17A by transferring the gene encoding it into CT26 colon cancer cells, either in a secretory or a membrane-bound form. Expression of the membrane-bound form on CT26 cells dramatically enhanced their proliferation in vitro. The enhanced growth was shown to be due to an increased rate of cell cycle progression: after synchronizing cells by adding and withdrawing colcemid, the rate of cell cycle progression in the cells expressing the membrane-bound form of IL-17A was much faster than that of the control cells. Both secretory and membrane-bound IL-17A induced the expression of Sca-1 in the cancer cells. When tumor clones were grafted into syngeneic BALB/c mice, the tumor clones expressing the membrane bound form IL-17A grew rapidly; those expressing the secretory form also grew faster than the wild type CT26 cells, but slower than the clones expressing the membrane-bound form. These results indicate that IL-17A promotes tumorigenicity by enhancing cell cycle progression. This finding should be considered in treating tumors and immune-related diseases. PMID- 27378227 TI - A Pair of Oviduct-Born Pickpocket Neurons Important for Egg-Laying in Drosophila melanogaster. AB - During copulation, male Drosophila transfers Sex Peptide (SP) to females where it acts on internal sensory neurons expressing pickpocket (ppk). These neurons induce a post-mating response (PMR) that includes elevated egg-laying and refractoriness to re-mating. Exactly how ppk neurons regulate the different aspects of the PMR, however, remains unclear. Here, we identify a small subset of the ppk neurons which requires expression of a pre-mRNA splicing factor CG3542 for egg-laying, but not refractoriness to mating. We identify two CG3542-ppk expressing neurons that innervate the upper oviduct and appear to be responsible for normal egg-laying. Our results suggest specific subsets of the ppk neurons are responsible for each PMR component. PMID- 27378228 TI - Is it a matter of urgency? A survey of assessments by walk-in patients and doctors of the urgency level of their encounters at a general emergency outpatient clinic in Oslo, Norway. AB - BACKGROUND: Emergency room (ER) use is increasing in several countries. Variability in the proportion of non-urgent ER visits was found to range from 5 to 90 % (median 32 %). Non-urgent emergency visits are considered an inappropriate and inefficient use of the health-care system because they may lead to higher expenses, crowding, treatment delays, and loss of continuity of health care provided by a general practitioner. Urgency levels of doctor-walk-in patient encounters were assessed based on their region of origin in a diverse Norwegian population. METHODS: An anonymous, multilingual questionnaire was distributed to all walk-in patients at a general emergency outpatient clinic in Oslo during two weeks in September 2009. We analysed demographic data, patient-doctor assessments of the level of urgency, and the results of the consultation. We used descriptive statistics to obtain frequencies with 95 % confidence interval (CI) for assessed levels of urgency and outcomes. Concordance between the patients' and doctors' assessments was analysed using a Kendall tau-b test. We used binary logistic regression modelling to quantify associations of explanatory variables and outcomes according to urgency level assessments. RESULTS: The analysis included 1821 walk-in patients. Twenty-four per cent of the patients considered their emergency consultation to be non-urgent, while the doctors considered 64 % of encounters to be non-urgent. The concordance between the assessments by the patient and by their doctor was positive but low, with a Kendall tau-b coefficient of 0.202 (p < 0.001). Adjusted logistic regression analysis showed that patients from Eastern Europe (odds ratio (OR) = 3.04; 95 % CI 1.60-5.78), Asia and Turkey (OR = 4.08; 95 % CI 2.43-6.84), and Africa (OR = 8.47; 95 % CI 3.87-18.5) reported significantly higher urgency levels compared with Norwegians. The doctors reported no significant difference in assessment of urgency based on the patient's region of origin, except for Africans (OR = 0.64; 95 % CI 0.43 0.96). CONCLUSION: This study reveals discrepancies between assessments by walk in patients and doctors of the urgency level of their encounters at a general emergency clinic. The patients' self-assessed perception of the urgency level was related to their region of origin. PMID- 27378229 TI - Modeling of successive cancer risks in Lynch syndrome families in the presence of competing risks using copulas. AB - In this article, we propose an association model to estimate the penetrance (risk) of successive cancers in the presence of competing risks. The association between the successive events is modeled via a copula and a proportional hazards model is specified for each competing event. This work is motivated by the analysis of successive cancers for people with Lynch Syndrome in the presence of competing risks. The proposed inference procedure is adapted to handle missing genetic covariates and selection bias, induced by the data collection protocol of the data at hand. The performance of the proposed estimation procedure is evaluated by simulations and its use is illustrated with data from the Colon Cancer Family Registry (Colon CFR). PMID- 27378230 TI - Assessing quality of life of self-reported rheumatic patients. AB - The aims of this study were to assess the health-related quality of life (HRQoL) in patients with self-reported rheumatic diseases (RD), to classify self-reported rheumatic patients in groups according to their health state and to explore the associations between health status and sociodemographic variables. Data came from the Portuguese Epidemiologic study of the RD. A sample of the Portuguese population aged 18 or more (n = 10,661) stratified by region and locality dimension was interviewed by trained interviewers and answered a standardized questionnaire that included the SF-36v1, the EQ-5D-3L, medical history, identification of potential rheumatic diseases, sociodemographic characteristics, among others. Descriptive statistics and parametric tests were used to compare HRQoL of respondents with and without RD. Comparisons with normative data from the Portuguese population were also carried out. A cluster analysis was used to classify respondents into homogeneous groups. Regression analyses were used to identify factors associated with HRQoL. Respondents with self-reported RD assigned a lower self-perception to their health status. The burden of disease was observed mainly in physical function, role physical and bodily pain. The EQ 5D-3L dimensions show similar results: the intensity of problems is significantly more evident in respondents with self-reported RD. HRQoL of respondents with self reported RD is related to sociodemographic variables and is significantly lower when compared with the Portuguese population. Four clusters of homogeneous respondents with self-reported RD were formed and characterized according to a number of variables. Factors associated with HRQoL were identified. In conclusion, suffering from a self-reported RD has a significant impact on self perceived health status and on the quality of life. PMID- 27378231 TI - Accounting for treatment by center interaction in sample size determinations and the use of surrogate outcomes in the pessary for the prevention of preterm birth trial: a simulation study. AB - BACKGROUND: The Pessary for the Prevention of Preterm Birth Study (PS3) is an international, multicenter, randomized clinical trial designed to examine the effectiveness of the Arabin pessary in preventing preterm birth in pregnant women with a short cervix. During the design of the study two methodological issues regarding power and sample size were raised. Since treatment in the Standard Arm will vary between centers, it is anticipated that so too will the probability of preterm birth in that arm. This will likely result in a treatment by center interaction, and the issue of how this will affect the sample size requirements was raised. The sample size requirements to examine the effect of the pessary on the baby's clinical outcome was prohibitively high, so the second issue is how best to examine the effect on clinical outcome. The approaches taken to address these issues are presented. RESULTS: Simulation and sensitivity analysis were used to address the sample size issue. The probability of preterm birth in the Standard Arm was assumed to vary between centers following a Beta distribution with a mean of 0.3 and a coefficient of variation of 0.3. To address the second issue a Bayesian decision model is proposed that combines the information regarding the between-treatment difference in the probability of preterm birth from PS3 with the data from the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study that relate preterm birth and perinatal mortality/morbidity. The approach provides a between-treatment comparison with respect to the probability of a bad clinical outcome. The performance of the approach was assessed using simulation and sensitivity analysis. Accounting for a possible treatment by center interaction increased the sample size from 540 to 700 patients per arm for the base case. The sample size requirements increase with the coefficient of variation and decrease with the number of centers. Under the same assumptions used for determining the sample size requirements, the simulated mean probability that pessary reduces the risk of perinatal mortality/morbidity is 0.98. The simulated mean decreased with coefficient of variation and increased with the number of clinical sites. CONCLUSION: Employing simulation and sensitivity analysis is a useful approach for determining sample size requirements while accounting for the additional uncertainty due to a treatment by center interaction. Using a surrogate outcome in conjunction with a Bayesian decision model is an efficient way to compare important clinical outcomes in a randomized clinical trial in situations where the direct approach requires a prohibitively high sample size. PMID- 27378232 TI - Relative importance of the determinants of serum levels of 25-hydroxy vitamin D in patients with chronic kidney disease. AB - INTRODUCTION: The cause of vitamin D deficiency in chronic kidney disease (CKD) is probably multi-factorial; however, the relative importance of each potential determinant is uncertain. AIMS: To determine factors associated with serum levels of 25-hydroxy vitamin D (25OHD) and their relative importance in a cohort of pre dialysis CKD patients. MATERIAL AND METHODS: Incident patients admitted to a CKD outpatient clinic were included. Those who were receiving vitamin D supplements or anticonvulsants were excluded. In addition to demographic and clinical data, information about outdoor physical activity, season of blood collection, prescription of statins, anti-angiotensin drugs and xanthine-oxidase inhibitors were included as potential determinants. Johnson's relative weights analysis was used to estimate the relative importance of each potential determinant and the results were expressed as percentage contribution to multiple R. RESULTS: The study group consisted of 397 patients, 30 of whom were excluded. The mean serum level of 25OHD was 13.7+/-7.4ng/ml, and 81% of patients had serum levels lower than 20ng/ml. By multiple linear regression and relative weights analyses, the best determinants of low serum 25OHD levels and their relative importance were: higher proteinuria (28.5%), old age (21.4%), low physical activity (19.4%), female gender (19.3%) and low serum bicarbonate levels (11.4%). CONCLUSIONS: Proteinuria and age are the determinants with the highest relative importance for predicting 25OHD levels in CKD patients. PMID- 27378233 TI - An Investigation of the Relationship Between the Alliance Negotiation Scale and Psychotherapy Process and Outcome. AB - OBJECTIVE: This study examines the validity of the Alliance Negotiation Scale (ANS) in a psychotherapy research program. Analyses were designed to evaluate the relationship between the ANS and psychotherapy process and outcome variables. METHOD: Data were collected in a metropolitan psychotherapy research program. Participants completed 30 sessions of therapy, postsession assessments, and a battery of measures at intake and termination. RESULTS: Relationships were found between the ANS and session outcome, working alliance, and the presence of ruptures and their resolution. Relationships emerged between the ANS and treatment outcome on measures of psychiatric distress and interpersonal problems. CONCLUSIONS: The ANS demonstrated relationships with several psychotherapy process and outcome variables. The ANS was the most differentiated from the working alliance on measures of interpersonal functioning and in discriminating personality disorder pathology. These results extend previous findings on the ANS' psychometric integrity, and offer new data on the relationship between negotiation and treatment outcome. PMID- 27378234 TI - Arbitrarily tunable orbital angular momentum of photons. AB - Orbital angular momentum (OAM) of photons, as a new fundamental degree of freedom, has excited a great diversity of interest, because of a variety of emerging applications. Arbitrarily tunable OAM has gained much attention, but its creation remains still a tremendous challenge. We demonstrate the realization of well-controlled arbitrarily tunable OAM in both theory and experiment. We present the concept of general OAM, which extends the OAM carried by the scalar vortex field to the OAM carried by the azimuthally varying polarized vector field. The arbitrarily tunable OAM we presented has the same characteristics as the well defined integer OAM: intrinsic OAM, uniform local OAM and intensity ring, and propagation stability. The arbitrarily tunable OAM has unique natures: it is allowed to be flexibly tailored and the radius of the focusing ring can have various choices for a desired OAM, which are of great significance to the benefit of surprising applications of the arbitrary OAM. PMID- 27378235 TI - Chlorogenic Acid Extends the Lifespan of Caenorhabditis elegans via Insulin/IGF-1 Signaling Pathway. AB - Coffee and tea, two of the most popular drinks around the world, share many in common from chemical components to beneficial effects on human health. One of their shared components, the polyphenols, most notably chlorogenic acid (CGA), was supposed to account for many of the beneficial effects on ameliorating diseases occurred accompanying people aging, such as the antioxidant effect and against diabetes and cardiovascular disease. CGA is also present in many traditional Chinese medicines. However, the mechanism of these effects was vague. The aging signaling pathways were conservative from yeast and worms to mammals. So, we tested if CGA had an effect on aging in Caenorhabditis elegans. We found that CGA could extend the lifespan of C. elegans by up to 20.1%, delay the age related decline of body movement, and improve stress resistance. We conducted genetic analysis with a series of worm mutants and found that CGA could extend the lifespan of the mutants of eat-2, glp-1, and isp-1, but not of daf-2, pdk-1, akt-1, akt-2, sgk-1, and clk-1. CGA could activate the FOXO transcription factors DAF-16, HSF-1, SKN-1, and HIF-1, but not SIR-2.1. Taken together, CGA might extend the lifespan of C. elegans mainly via DAF-16 in insulin/IGF-1 signaling pathway. PMID- 27378238 TI - Identification of Epigenetic Factor Proteins Expressed in Human Embryonic Stem Cell-Derived Trophoblasts and in Human Placental Trophoblasts. AB - Human embryonic stem cells (hESCs) have been used to derive trophoblasts through differentiation in vitro. Intriguingly, mouse ESCs are prevented from differentiation to trophoblasts by certain epigenetic factor proteins such as Dnmt1, thus necessitating the study of epigenetic factor proteins during hESC differentiation to trophoblasts. We used stable isotope labeling by amino acids in cell culture and quantitative proteomics to study changes in the nuclear proteome during hESC differentiation to trophoblasts and identified changes in the expression of 30 epigenetic factor proteins. Importantly, the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B were downregulated. Additionally, we hypothesized that nuclear proteomics of hESC-derived trophoblasts may be used for screening epigenetic factor proteins expressed by primary trophoblasts in human placental tissue. Accordingly, we conducted immunohistochemistry analysis of six epigenetic factor proteins identified from hESC-derived trophoblasts-DNMT1, DNMT3B, BAF155, BAF60A, BAF57, and ING5-in 6-9 week human placentas. Indeed, expression of these proteins was largely, though not fully, consistent with that observed in 6-9 week placental trophoblasts. Our results support the use of hESC derived trophoblasts as a model for placental trophoblasts, which will enable further investigation of epigenetic factors involved in human trophoblast development. PMID- 27378239 TI - Lung Cancer Deaths in the National Lung Screening Trial Attributed to Nonsolid Nodules. AB - Purpose To validate the recommendation of performing annual follow-up of nonsolid nodules (NSNs) identified by computed tomographic (CT) screening for lung cancer, all cases of lung cancer manifesting as NSN in the National Lung Screening Trial (NLST) were reviewed. Materials and Methods Institutional review board and informed consent were waived for this study. The NLST database was searched to identify all participants with at least one NSN on CT scan with lung cancer as the cause of death (COD) documented by the NLST endpoint verification process. Among the 26 722 participants, 2534 (9.4%) had one or more NSNs, and lung cancer as the COD occurred for 48 participants. On review, 21 of the 48 patients had no NSN in the cancerous lobe, which left 27 patients whose CT scans were reviewed by four radiologists: Group A (n = 12) were cases of lung cancer as the COD because of adenocarcinoma, and group B (n = 15) were cases of lung cancer as the COD because of other cell types. Frequency of lung cancer as the COD because of NSN and the time from randomization to diagnosis within these groups was determined. Results Six of the 12 patients in group A had no NSN in the cancerous lobe whereas the remaining six patients had a dominant solid or part-solid nodule in the lobe that rapidly grew in four patients, was multifocal in one patient, and had a growing NSN in one patient in whom diagnosis was delayed for over 3 years. Five of the 15 patients in group B had no NSN, and for the remaining 10 patients, lung cancer as the COD was not because of NSN. Conclusion It seems unlikely that patients with lung cancer as the COD occurred with solitary or dominant NSN as long as annual follow-up was performed. This lends further support that lung cancers that manifest as NSNs have an indolent course and can be managed with annual follow-up. (c) RSNA, 2016. PMID- 27378236 TI - Oral Delivery of Protein Drugs Bioencapsulated in Plant Cells. AB - Plants cells are now approved by the FDA for cost-effective production of protein drugs (PDs) in large-scale current Good Manufacturing Practice (cGMP) hydroponic growth facilities. In lyophilized plant cells, PDs are stable at ambient temperature for several years, maintaining their folding and efficacy. Upon oral delivery, PDs bioencapsulated in plant cells are protected in the stomach from acids and enzymes but are subsequently released into the gut lumen by microbes that digest the plant cell wall. The large mucosal area of the human intestine offers an ideal system for oral drug delivery. When tags (receptor-binding proteins or cell-penetrating peptides) are fused to PDs, they efficiently cross the intestinal epithelium and are delivered to the circulatory or immune system. Unique tags to deliver PDs to human immune or nonimmune cells have been developed recently. After crossing the epithelium, ubiquitous proteases cleave off tags at engineered sites. PDs are also delivered to the brain or retina by crossing the blood-brain or retinal barriers. This review highlights recent advances in PD delivery to treat Alzheimer's disease, diabetes, hypertension, Gaucher's or ocular diseases, as well as the development of affordable drugs by eliminating prohibitively expensive purification, cold chain and sterile delivery. PMID- 27378237 TI - Morpholino-mediated Knockdown of DUX4 Toward Facioscapulohumeral Muscular Dystrophy Therapeutics. AB - Derepression of DUX4 in skeletal muscle has emerged as a likely cause of pathology in facioscapulohumeral muscular dystrophy (FSHD). Here we report on the use of antisense phosphorodiamidate morpholino oligonucleotides to suppress DUX4 expression and function in FSHD myotubes and xenografts. The most effective was phosphorodiamidate morpholino oligonucleotide FM10, which targets the polyadenylation signal of DUX4. FM10 had no significant cell toxicity, and RNA seq analyses of FSHD and control myotubes revealed that FM10 down-regulated many transcriptional targets of DUX4, without overt off-target effects. Electroporation of FM10 into FSHD patient muscle xenografts in mice also down regulated DUX4 and DUX4 targets. These findings demonstrate the potential of antisense phosphorodiamidate morpholino oligonucleotides as an FSHD therapeutic option. PMID- 27378240 TI - Photodegradation of the azole fungicide climbazole by ultraviolet irradiation under different conditions: Kinetics, mechanism and toxicity evaluation. AB - Climbazole (CZ) has been known to persist in various environmental media, and may cause potential risks to aquatic organisms. This study investigated the photodegradation of CZ by ultraviolet (UV, 254nm) under different conditions. The results revealed that CZ could be effectively degraded in aqueous solutions under UV-254 irradiation with a half-life of 9.78min (pH=7.5), and the photodegradation followed pseudo-first-order kinetics. pH had almost no effect on its rate constants and quantum yields; but the water quality of natural waters could affect the photolysis of CZ, and the coexisting constituents such as Fe(3+), NO3( ), and HA obviously inhibited its photolysis. The addition of different radical scavengers also inhibited the photodegradation of CZ due to the reduction of reactive oxygen species (ROS). CZ underwent direct and self-sensitized photolysis involving ROS. Based on the identified photodegradation by-products, the proposed pathways included hydroxylative dechlorination, dechlorination and de-pinacolone. Moreover, toxicity evaluation using duckweed found significant toxicity reduction in the photodegradation system of CZ after the irradiation of UV-254, and the remaining by-products did not pose extra toxicity compared with CZ itself. These findings from present study suggest that CZ in effluent could be further reduced by applying UV photolysis treatment. PMID- 27378241 TI - Two-year clinical comparison of a flowable-type nano-hybrid composite and a paste type composite in posterior restoration. AB - AIM: The purpose of the present study was to compare the clinical efficacy between a flowable-type nano-hybrid composite and a paste-type composite for posterior restoration. METHODS: Of 62 posterior teeth in 33 patients (mean age: 34.1 years), 31 were filled with a paste-type composite (Heliomolar [HM] group), and another 31 with a flowable nano-hybrid composite (MI FIL [MI] group). Clinical efficacy was evaluated at 2 years after the restoration. RESULTS: There were no differences for retention, surface texture deterioration, anatomical form change, deterioration of marginal adaptation, and secondary caries, while a statistical difference was found for marginal discoloration, which was significantly greater in the HM group (P < 0.05). Furthermore, color matching in the MI group was superior to that in the HM group immediately after the restoration throughout the study period. CONCLUSIONS: The present 2-year clinical evaluation of different composites showed that the flowable nano-hybrid composite could be an effective esthetic material for posterior restoration. PMID- 27378242 TI - EYA4 functions as tumor suppressor gene and prognostic marker in pancreatic ductal adenocarcinoma through beta-catenin/ID2 pathway. AB - Eye absent homolog 4 (EYA4) was initially found as key gene in controlling eye development in Drosophila. We recently found that EYA4 was an independent prognostic factor in hepatocellular carcinoma. Its biological functions in malignancies remained unknown. The present study aimed at investigating its biological functions, molecular mechanisms and prognostic values in pancreatic ductal adenocarcinoma (PDAC). Overexpression of EYA4 in PDAC cells inhibited proliferation and invasion in vitro and tumor growth in vivo. Depletion of EYA4 in PDAC cells enhanced proliferation and invasion in vitro and tumor growth in vivo. Mechanistically, armed with the serine/threonine-specific protein phosphatase activity, EYA4 dephosphorylated beta-catenin at Ser675, blocked beta catenin nuclear translocation and inhibited ID2 transactivation. Consistently, EYA4 expression inversely correlated with the levels of p-Ser675-beta-catenin and ID2 in tissues. EYA4 expression in PDAC tissues was significantly reduced as compared with adjacent non-tumoral tissues. EYA4 expression was an independent prognostic factor in PDAC, with a lower EYA4 level in association with shorter long-term survival and disease-free time. We showed that EYA4 functioned as tumor suppressor gene in PDAC via repressing beta-catenin/ID2 activation, and was an independent prognostic factor in PDAC. PMID- 27378243 TI - Apigenin inhibits the inducible expression of programmed death ligand 1 by human and mouse mammary carcinoma cells. AB - Programmed death ligand 1 (PD-L1) is expressed by many cancer cell types, as well as by activated T cells and antigen-presenting cells. Constitutive and inducible PD-L1 expression contributes to immune evasion by breast cancer (BC) cells. We show here that the dietary phytochemical apigenin inhibited interferon (IFN) gamma-induced PD-L1 upregulation by triple-negative MDA-MB-468 BC cells, HER2(+) SK-BR-3 BC cells, and 4T1 mouse mammary carcinoma cells, as well as human mammary epithelial cells, but did not affect constitutive PD-L1 expression by triple negative MDA-MB-231 BC cells. IFN-beta-induced expression of PD-L1 by MDA-MB-468 cells was also inhibited by apigenin. In addition, luteolin, the major metabolite of apigenin, inhibited IFN-gamma-induced PD-L1 expression by MDA-MB-468 cells. Apigenin-mediated inhibition of IFN-gamma-induced PD-L1 expression by MDA-MB-468 and 4T1 cells was associated with reduced phosphorylation of STAT1, which was early and transient at Tyr701 and sustained at Ser727. Apigenin-mediated inhibition of IFN-gamma-induced PD-L1 expression by MDA-MB-468 cells also increased proliferation and interleukin-2 synthesis by PD-1-expressing Jurkat T cells that were co-cultured with MDA-MB-468 cells. Apigenin therefore has the potential to increase the vulnerability of BC cells to T cell-mediated anti-tumor immune responses. PMID- 27378244 TI - Infrared Photodissociation Spectroscopy of C4 N- , C6 N- and C8 N. AB - The gas-phase vibrational spectroscopy of cold C2n N- (n=2-4) anions is investigated in the CC and CN multiple bond stretching region (1700-2250 cm-1 ) by means of infrared photodissociation (IRPD) spectroscopy in a cryogenically cooled ion trap of the corresponding messenger-tagged complexes. The IRPD spectra are assigned to N-terminated linear structures with triplet ground states (3 Sigma- ) based on a comparison with harmonic vibrational frequencies and intensities from density functional theory computations. In contrast to the polyacetylenic C2n+1 N- anions, the linear C-C chains investigated here exhibit cumulenic character, which is most pronounced in C4 N- and decreases with chain length. Additional intense transitions are observed for C6 N- above 3000 cm-1 and are attributed to overtone and combination bands involving the CC stretching modes, based on anharmonic computations. The influence of a D2 tag on the vibrational features of C2n N- anions is shown to be small. PMID- 27378245 TI - Increased risk of hospital admission for dehydration or heat-related illness after initiation of medicines: a sequence symmetry analysis. AB - WHAT IS KNOWN AND OBJECTIVE: Although several studies have identified factors which increase the risk of heat-related illness, few have assessed the contribution of medicines. To address this knowledge gap, our study aimed to assess the risk of hospital admission for dehydration or other heat-related illness following initiation of medicines. METHODS: We conducted a retrospective analysis using prescription event symmetry analysis (PESA) of 6700 veterans with incident hospital admission for dehydration or heat-related illness (ICD-10-AM codes E86, X30, T67), between 1 January 2001 and 30 June 2013. The main outcome measure was first ever hospital admission for dehydration or heat-related illness following initiation of commonly used medicines. RESULTS AND DISCUSSION: A significantly higher risk of incident hospital admission for dehydration or heat related illness was observed following initiation of anticoagulants, cardiovascular medicines, NSAIDs, antipsychotics, antidepressants and anticholinergic agents. The risk of hospital admission for dehydration or heat related illness ranged from 1.17 (SSRIs) to 2.79 (ACEI plus diuretic combination product). No significant association was observed between initiation of anticonvulsants, anti-Parkinson's agents, hypnotics, anxiolytics or antihistamines and hospital admission for dehydration or heat-related illness. WHAT IS NEW AND CONCLUSION: Many commonly used medicines were found to be associated with increased risk of hospitalization for dehydration or heat-related illness. Initiation of ACE inhibitors in combination with diuretics had the highest risk. Prescribers and patients should be aware of the potential for medicines to be associated with increased risk of dehydration and heat-related illness. PMID- 27378246 TI - Multiple sequential light and laser sources to activate aminolevulinic acid for rosacea. AB - BACKGROUND AND AIMS: The use of multiple, sequential light and laser sources for topical ALA activation in photodynamic therapy (PDT) of rosacea has been largely absent from the literature. The aim of this study was to evaluate ALA-PDT for rosacea using blue light sequentially with red light, pulsed-dye laser (PDL), and/or intense pulsed light (IPL). PATIENTS/METHODS: Thirty patients (39 treatments) were enrolled in this retrospective, single-center study. Treatment groups included blue light + PDL, blue light + IPL, blue light + PDL + IPL, or blue light + red light + PDL + IPL. Patient-reported outcome measures (incidence of adverse events, improvement in rosacea, and improvement in overall skin quality) were obtained via a telephone questionnaire and graded on a 4-point scale. RESULTS: There was no statistically significant difference in patient reported rosacea or overall skin quality improvement. Apart from decreased peeling following blue light + IPL compared to blue light + PDL (P = 0.041) and blue light + IPL + PDL (P = 0.005), there were no other statistically significant differences in postprocedure adverse events. CONCLUSIONS: The use of multiple, sequential light and laser sources with ALA-PDT for rosacea, while well tolerated, did not lead to statistically significant improvements in patient reported efficacy. Although this retrospective study is limited by a small sample size with disparate patient numbers between groups and no physician-evaluated outcome criteria, it does demonstrate that multiple light sources with PDT can be safely used in a single session. PMID- 27378247 TI - Corticosteroid-related adverse events in patients with giant cell arteritis: A claims-based analysis. AB - OBJECTIVE: Corticosteroids (CS) are standard treatment for giant cell arteritis (GCA), but concerns persist over toxicities associated with long-term use. In this retrospective study of medical claims data, we estimated risks for adverse events (AEs) in CS-treated GCA patients. METHODS: Cox regression analyses with CS use as a time-dependent variable were conducted on data from the 2003 to 2012 Truven Health Analytics MarketScan Database. Patients 50 years of age and older who had >=2 claims of newly diagnosed GCA, >=1 filled oral CS prescription, and no AEs before GCA diagnosis were included. The primary outcome was presence of a new CS-related AE. RESULTS: In total, 2497 patients were included. Their mean age was 71.0 years, and 71% were women. Follow-up was 9680 patient-years (PY). CS treatment continued for a mean (SD) of 1.196 (729.2) days; mean (SD) prescribed cumulative CS dose was 6983.3mg (6519.9). The overall AE rate was 0.43 events/PY; the most frequent AEs were cataract and bone disease. For each 1000-mg increase in CS exposure, the hazard ratio (HR) increased by 3% (HR = 1.03; 95% CI: 1.02 1.05; P < 0.001). Additionally, statistically significant individual associations between increased CS exposure and AE risk were observed for bone-related AEs (P < 0.001), cataract (P < 0.001), glaucoma (P = 0.005), pneumonia (P = 0.003), and diabetes mellitus (P < 0.001 in a subset of patients with no previous history of diabetes). CONCLUSION: CS exposure significantly increased risk for potentially serious AEs, emphasizing a need for new treatment options for GCA patients. PMID- 27378248 TI - The gas chromatographic analysis of the reaction products of the partial isobutane oxidation as a two phase process. AB - The partial oxidation of isobutane to t-butyl hydroperoxide (TBHP) has been studied analytically for the first time as a two-phase process in a capillary micro reactor. In order to obtain detailed information on products, yields, selectivities and reaction pathways, the products have been investigated by GC/MS. An Rxi-5ms column and a PTV-injector have been used to analyze the liquid products. TBHP, di-t-butyl peroxide (DTBP), t-butanol (TBA), and propanone as main products as well as further by-products e.g. methanal, isopropanol, isobutanol and isobutanal in minor quantities have been identified by MS. The liquid products have been obtained by quenching the reaction and vaporizing the isobutane afterwards by pressure reduction using a mass flow controller allowing a constant mass flow. For all liquid reaction products calibrations, a validation of the method including limits of quantification and detection as well as calculation of uncertainties has been performed. The results have been applied successfully for the investigation of the selectivities of the main products (TBHP, DTBP, TBA, propanone) of the isobutane oxidation. In the frame of the analytical investigation of this reaction a correlation coefficient of r(2)>0.999 for TBHP and DTBP, which is necessary to perform a validation, has been obtained for the first time. The gaseous phase has been analyzed using a GASPRO column, a DEANS switch, a mole sieve column and a TCD detector. Apart from the gaseous reactants, isobutene has been found. PMID- 27378249 TI - Water-compatible dummy molecularly imprinted resin prepared in aqueous solution for green miniaturized solid-phase extraction of plant growth regulators. AB - A water-compatible dummy molecularly imprinted resin (MIR) was synthesized in water using melamine, urea, and formaldehyde as hydrophilic monomers of co polycondensation. A triblock copolymer (PEO-PPO-PEO, P123) was used as porogen to dredge the network structure of MIR, and N-(1-naphthyl) ethylenediamine dihydrochloride, which has similar shape and size to the target analytes, was the dummy template of molecular imprinting. The obtained MIR was used as the adsorbent in a green miniaturized solid-phase extraction (MIR?mini-SPE) of plant growth regulators, and there was no organic solvent used in the entire MIR?mini SPE procedure. The calibration linearity of MIR?mini-SPE?HPLC method was obtained in a range 5?250ngmL(?1) for IAA, IPA, IBA, and NAA with correlation coefficient (r) ?0.9998. Recoveries at three spike levels are in the range of 87.6?100.0% for coconut juice with relative standard deviations ?8.1%. The MIR?mini-SPE method possesses the advantages of environmental friendliness, simple operation, and high efficiency, so it is potential to apply the green pretreatment strategy to extraction of trace analytes in aqueous samples. PMID- 27378250 TI - Comparison of liquid and supercritical fluid chromatography mobile phases for enantioselective separations on polysaccharide stationary phases. AB - Analysis and production of enantiomerically pure compounds is a major topic of interest when active pharmaceutical ingredients are concerned. Enantioselective chromatography has become a favourite both at the analytical and preparative scales. High-performance liquid chromatography (HPLC) and supercritical fluid chromatography (SFC) are dominating the scene and are often seen as complementary techniques. Nowadays, for economic and ecologic reasons, SFC may be preferred over normal-phase HPLC (NPLC) as it allows significant reductions in solvent consumption. However, the transfer of NPLC methods to SFC is not always straightforward. In this study, we compare the retention of achiral molecules and separation of enantiomers under supercritical fluid (carbon dioxide with ethanol or isopropanol) and liquid normal-phase (heptane with ethanol or isopropanol) elution modes with polysaccharide stationary phases in order to explore the differences between the retention and enantioseparation properties between the two modes. Chemometric methods (namely quantitative structure-retention relationships and discriminant analysis) are employed to compare the results obtained on a large set of analytes (171 achiral probes and 97 racemates) and gain some understanding on the retention and separation mechanisms. The results indicate that, contrary to popular belief, carbon dioxide - solvent SFC mobile phases are often weaker eluents than liquid mobile phases. It appears that SFC and NPLC elution modes provide different retention mechanisms. While some enantioseparations are unaffected, facilitating the transfer between the two elution modes, other enantioseparations may be drastically different due to different types and strength of interactions contributing to enantioselectivity. PMID- 27378251 TI - Linear modeling of the soil-water partition coefficient normalized to organic carbon content by reversed-phase thin-layer chromatography. AB - Soil-water partition coefficient normalized to the organic carbon content (KOC) is one of the crucial properties influencing the fate of organic compounds in the environment. Chromatographic methods are well established alternative for direct sorption techniques used for KOC determination. The present work proposes reversed-phase thin-layer chromatography (RP-TLC) as a simpler, yet equally accurate method as officially recommended HPLC technique. Several TLC systems were studied including octadecyl-(RP18) and cyano-(CN) modified silica layers in combination with methanol-water and acetonitrile-water mixtures as mobile phases. In total 50 compounds of different molecular shape, size, and various ability to establish specific interactions were selected (phenols, beznodiazepines, triazine herbicides, and polyaromatic hydrocarbons). Calibration set of 29 compounds with known logKOC values determined by sorption experiments was used to build simple univariate calibrations, Principal Component Regression (PCR) and Partial Least Squares (PLS) models between logKOC and TLC retention parameters. Models exhibit good statistical performance, indicating that CN-layers contribute better to logKOC modeling than RP18-silica. The most promising TLC methods, officially recommended HPLC method, and four in silico estimation approaches have been compared by non-parametric Sum of Ranking Differences approach (SRD). The best estimations of logKOC values were achieved by simple univariate calibration of TLC retention data involving CN-silica layers and moderate content of methanol (40-50%v/v). They were ranked far well compared to the officially recommended HPLC method which was ranked in the middle. The worst estimates have been obtained from in silico computations based on octanol-water partition coefficient. Linear Solvation Energy Relationship study revealed that increased polarity of CN-layers over RP18 in combination with methanol-water mixtures is the key to better modeling of logKOC through significant diminishing of dipolar and proton accepting influence of the mobile phase as well as enhancing molar refractivity in excess of the chromatographic systems. PMID- 27378252 TI - Aggregation behaviour of biohybrid microgels from elastin-like recombinamers. AB - Investigation of the aggregation behavior of biohybrid microgels, which can potentially be used as drug carriers, is an important topic, because aggregation not only causes loss of activity, but also toxicity and immunogenicity. To study this effect we synthesized microgels from elastin-like recombinamers (ELRs) using the miniemulsion technique. The existence of aggregation for such biohybrid microgels at different concentrations and temperatures was studied by different methods which include dynamic light scattering (DLS), (1)H high-resolution magic angle sample spinning (HRMAS) NMR spectroscopy, relaxometry and diffusometry. A hysteresis effect was detected in the process of aggregation by DLS as a function of temperature that strongly depends on ELR microgel concentration. The aggregation process was further quantitatively analyzed by the concentration dependence of the (1)H amino-acid residue chemical shifts and microgel diffusivity measured by NMR methods using the population balance kinetic aggregation model. PMID- 27378253 TI - Novel semi-dry electrodes for brain-computer interface applications. AB - OBJECTIVES: Modern applications of brain-computer interfaces (BCIs) based on electroencephalography rely heavily on the so-called wet electrodes (e.g. Ag/AgCl electrodes) which require gel application and skin preparation to operate properly. Recently, alternative 'dry' electrodes have been developed to increase ease of use, but they often suffer from higher electrode-skin impedance and signal instability. In the current paper, we have proposed a novel porous ceramic based 'semi-dry' electrode. The key feature of the semi-dry electrodes is that their tips can slowly and continuously release a tiny amount of electrolyte liquid to the scalp, which provides an ionic conducting path for detecting neural signals. APPROACH: The performance of the proposed electrode was evaluated by simultaneous recording of the wet and semi-dry electrodes pairs in five classical BCI paradigms: eyes open/closed, the motor imagery BCI, the P300 speller, the N200 speller and the steady-state visually evoked potential-based BCI. MAIN RESULTS: The grand-averaged temporal cross-correlation was 0.95 +/- 0.07 across the subjects and the nine recording positions, and these cross-correlations were stable throughout the whole experimental protocol. In the spectral domain, the semi-dry/wet coherence was greater than 0.80 at all frequencies and greater than 0.90 at frequencies above 10 Hz, with the exception of a dip around 50 Hz (i.e. the powerline noise). More importantly, the BCI classification accuracies were also comparable between the two types of electrodes. SIGNIFICANCE: Overall, these results indicate that the proposed semi-dry electrode can effectively capture the electrophysiological responses and is a feasible alternative to the conventional dry electrode in BCI applications. PMID- 27378254 TI - Evidence-Based Decision Making in Youth Mental Health Prevention. AB - Given the impressive amount of knowledge relevant to prevention efforts, this paper articulates strategies to capitalize on such knowledge through evidence based decision making. Knowledge, or "evidence," is understood here as coming from multiple sources, including research, individual people, group history, and relevant theory. The presented strategies to facilitate evidence-based decision making are: (1) intervention knowledge management; (2) collaborative design; (3) knowledge resources for intervention; and (4) developmentally sensitive training and supervision. Examples and benefits are outlined for each strategy. It is ultimately argued that evidence-based decision making embodies the scientific approach, and is worth consideration within primary prevention, given its early success in secondary intervention of youth mental health. PMID- 27378255 TI - Physical Activity During the Early Years: A Systematic Review of Correlates and Determinants. AB - CONTEXT: Being physically active during the early years (age 0-6 years) is vital for healthy development. Identifying correlates and determinants of physical activity (PA) is crucial to guide effective interventions. This systematic review synthesized studies investigating potential correlates and determinants of PA during the early years, accounting for different types of PA assessment. EVIDENCE ACQUISITION: Nine electronic databases were searched from inception year (1900) until September 2014; data were analyzed/interpreted in April 2015. The following inclusion criteria were used: written in English, published in peer-reviewed journals, participants not in statutory/school education, and an observational design investigating associations between an exposure/variable, and a quantitative measure of PA. Correlates/determinants of total, moderate to vigorous, and light PA were reported using an ecologic model. EVIDENCE SYNTHESIS: Of 22,045 identified studies, 130 were included. All took place in high-income countries and few (6%) were of high quality. Correlates of total PA were sex (male, ++); parental PA (+); parental support (+); and time outdoors (+). Determinants of total PA were sex (+) and time spent playing with parents (+). The only correlate of moderate to vigorous PA was sex (male, ++). No determinants of moderate to vigorous or light PA were found. PA correlates/determinants were relatively consistent between objective and subjective PA measures. CONCLUSIONS: Numerous studies investigated potential correlates and determinants of PA, but overall quality was low. A small number of demographic/biological and social/cultural factors were associated with PA. There is a need for high-quality studies exploring correlates/determinants across all domains of the ecologic model. PMID- 27378256 TI - Mobility and subcellular localization of endogenous, gene-edited Tau differs from that of over-expressed human wild-type and P301L mutant Tau. AB - Alzheimer's disease (AD) and a subset of frontotemporal dementia termed FTLD-Tau are characterized by a massive, yet incompletely characterized and understood redistribution of Tau. To establish a framework for understanding this pathology, we used the genome-editing tool TALEN and generated Tau-mEOS2 knock-in mice to determine the mobility and subcellular localization of endogenous Tau in hippocampal cultures. We analysed Tau in axons, dendrites and spines at three stages of maturation using live-cell imaging, photo-conversion and FRAP assays. Tau-mEOS2 cultures were compared with those over-expressing EGFP-tagged forms of human wild-type (hWT-Tau) and P301L mutant Tau (hP301L-Tau), modelling Tau accumulation in AD and FTLD-Tau, respectively. In developing neurons, Tau-mEOS2 followed a proximo-distal gradient in axons and a subcellular distribution similar to that of endogenous Tau in neurons obtained from wild-type mice, which were abolished, when either hWT-Tau or hP301L-Tau was over-expressed. For the three conditions, FRAP analysis revealed a similar mobility in dendrites compared with axons; however, Tau-mEOS2 was less mobile than hWT-Tau and hP301L-Tau and the mobile fraction was smaller, possibly reflecting less efficient microtubule binding of Tau when over-expressed. Together, our study presents Tau-mEOS2 mice as a novel tool for the study of Tau in a physiological and a pathological context. PMID- 27378257 TI - Inorganic Nano Light-Emitting Transistor: p-Type Porous Silicon Nanowire/n-Type ZnO Nanofilm. AB - An inorganic nano light-emitting transistor (INLET) consisting of p-type porous Si nanowires (PoSiNWs) and an n-type ZnO nanofilm was integrated on a heavily doped p-type Si substrate with a thermally grown SiO2 layer. To verify that modulation of the Fermi level of the PoSiNWs is key for switchable light emitting, I-V and electroluminescent characteristics of the INLET are investigated as a function of gate bias (V g ). As the V g is changed from 0 V to -20 V, the current level and light-emission intensity in the orange-red range increase by three and two times, respectively, with a forward bias of 20 V in the p-n junction, compared to those at a V g of 0 V. On the other hand, as the V g approaches 10 V, the current level decreases and the emission intensity is reduced and then finally switched off. This result arises from the modulation of the Fermi level of the PoSiNWs and the built-in potential at the p-n junction by the applied gate electric field. PMID- 27378259 TI - [Myotonic dystrophy in children; how can you recognise the symptoms in a child and in family members?]. AB - Myotonic dystrophy type 1 is an autosomal dominant disease, which affects multiple organ systems. Clinical symptoms in young children are non-specific, and include learning disabilities, behavioural problems and fatigue. Myotonic dystrophy type 1 is characterised by the phenomenon "anticipation": the occurrence of increasing severity of disease and lower age of onset in successive generations. Early diagnosis and treatment of early-onset symptoms in the patient and in family members is essential. Genetic counselling of all family members regarding hereditary risks is important. This article provides insight into the diagnosis of myotonic dystrophy in childhood. PMID- 27378258 TI - Prevalence of hepatocellular carcinoma in chronic hepatitis C patients in Mid Delta, Egypt: A single center study. AB - BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) has an increasing incidence worldwide. In this study we aimed to assess the prevalence of HCC among HCV patients in our center in Mid Delta, Egypt. PATIENTS AND METHODS: During the period between April 2013 and January 2015, we screened sequentially chronic HCV patients attending inpatient wards or outpatient Clinic of Tropical Medicine Department in Tanta University Hospital for HCC. Individuals with focal lesion in Ultrasound (US) and/or serum alpha-fetoprotein (AFP) level >200ng/ml were examined by triphasic computed tomography scanning (CT), and/or magnetic resonance imaging (MRI). RESULTS: Among 514 HCV patients interviewed and accepted sharing in this study, 90 (17.5%), 144 (28%), and 280 (54.5%) were Child A, B, and C, respectively. We found that 108/514 patients (21%) had focal lesion detected by US. Also, 89/514 (17.3%) had elevated AFP >200, 13 of them (14.6%) had no focal lesion on US, but further work up showed HCC in 2 of them. Overall HCC diagnosis was confirmed in 103 cases, 94 of them (91.3%) were Child B or C. Occurrence of HCC was significantly higher in smokers, diabetics, patients with decompensated liver and those with positive family history of HCC. Only 20/103 (19.4%) were candidates to curative treatments, 8 of them were Child A asymptomatic and discovered accidentally during screening. CONCLUSION: The high prevalence of HCC in our HCV patients (22%) was mainly associated with decompensated cirrhosis. A national surveillance program for the detection of HCC in cirrhotic HCV Egyptian patients by combining ultrasound examination and AFP is highly recommended. PMID- 27378260 TI - [Neurological symptoms with a hepatitis E virus infection]. AB - BACKGROUND: Infection with hepatitis E virus genotype 3 (HEV3) is an emerging zoonosis in the industrialized world. The infection usually proceeds asymptomatically. Extrahepatic sequelae including neurological symptoms have been described. CASE DESCRIPTION: A 52-year-old man presented at the emergency department with pain, muscle weakness and sensory disorders in both shoulders and arms. He was found to have bilateral neuralgic amyotrophy accompanying an HEV3 infection. CONCLUSION: An HEV3 infection can have neurological sequelae, but very little is known about its incidence and spectrum of symptoms. PMID- 27378261 TI - [Assessment of bleeding risk in patients with venous thromboembolism: we are still a long way from home]. AB - Recent American, European and Dutch guidelines recommend lifelong anticoagulation after a diagnosis of unprovoked venous thromboembolism (VTE) in the absence of high bleeding risk. Major bleeding events may, however, be devastating, and are reported to have a higher case fatality rate than recurrent venous thromboembolism itself. Unfortunately, there are no validated risk assessment tools for major bleeding that help physicians determine the optimal duration of anticoagulant therapy after VTE. Furthermore, the scarce studies on this subject have focused on vitamin K antagonist treatment regimens only, covering mainly the initial weeks and first month, during which period the level of anticoagulation is unstable. New studies focusing on bleeding risk during the 'chronic' treatment period with modern anticoagulants, i.e. the direct oral anticoagulants or 'DOACs', are urgently needed. Until these are available, the 2016 Dutch guideline on anticoagulation therapy provides a table with a summary of known individual risk factors that can be applied in clinical practice. PMID- 27378262 TI - [A woman with aswelling of the hallux]. AB - A 73-year-old woman presented at the Surgery department with a swelling at the base of the toe nail of her left hallux, 20 years after partial wedge resection because of onychocryptosis. We removed the swelling surgically. Histological examination of the tissue revealed a traumatic epithelial cyst. PMID- 27378263 TI - [Bifid rib: the importance of good radiological procedure]. AB - BACKGROUND: Bifid rib is a congenital abnormality occurring in about 0.6% of the healthy population. CASE DESCRIPTION: A 5-year-old boy attended the Orthopaedics outpatient clinic with a swelling on the right of his sternum that was increasing in size. A chest x-ray did not reveal any abnormalities. However, on the CT scan that was then performed we saw a bifurcation of the fourth rib, for which we adopted a watchful waiting treatment strategy. With hindsight, the bifurcation was also visible on the x-ray image but we had not initially recognised it as such. CONCLUSION: Bifurcation of a rib is not always recognised as such. Unnecessary supplementary diagnostics can be avoided with the use of a correctly implemented radiological procedure. PMID- 27378264 TI - [Asthma/COPD service in general practice. Study into feasibility and effectiveness]. AB - OBJECTIVE: A study of the effectiveness and functioning of an asthma/COPD service (AC service). DESIGN: Observational study. METHOD: General practitioners (GPs) in the northern part of the Netherlands can refer patients with airway symptoms to the AC service, which was set up in 2007 by local pulmonologists, GPs and the primary care laboratory CERTE. Before the assessment, patients fill in three questionnaires at home: the Clinical COPD Questionnaire (CCQ), the Asthma Control Questionnaire (ACQ) and a medical history list. The laboratory assesses lung function and a physical examination is carried out. All data is sent via the Internet to a pulmonologist, who advises the GP on diagnosis and treatment via an information system. The pulmonologist can offer a follow-up service if required. For this publication we had access to data from 14,748 registered patients and 3721 follow-up consultations. RESULTS: The pulmonologist diagnosed 6201 (42%) patients with asthma, 2728 (19%) with COPD and 1039 (7%) with 'asthma/COPD overlap syndrome'. The pulmonologist advised that 940 patients (6%) should have a change in medication and reassessment after 3 months. In this group, the number of unstable COPD patients (CCQ >= 1) dropped from 134 (67%) to 99 (50%). The number of patients with unstable asthma (ACQ >= 1.5) dropped from 245 (3%) to 137 (24%). For 1642 (11%) patients the pulmonologist advised no change in medication and the GP referred the patient for reassessment after 12 months. These patients were generally stable, with a slight improvement in smoking status, exacerbations and inhalation technique. CONCLUSION: Approximately 60% of all patients with asthma or COPD in this region were assessed by the AC service at least once in the period 2007-2014. Advice on diagnosis and treatment given to the GP resulted in better patient-related outcomes in both asthma and COPD patients. PMID- 27378265 TI - [An abnormal colour of a haemodialysis filter]. AB - In a 76-year-old man, the filter of the dialyser turned yellow instead of pink after haemodialysis. He had no complaints, but physical examination revealed mild jaundice and his serum bilirubin was elevated. A CT scan of the abdomen showed a pancreatic neoplasm. Discoloration of a filter of the dialyser might thus be a first sign of painless icterus. PMID- 27378266 TI - [The crux of the sacroiliac joint]. AB - Pain from the sacroiliac (SI) joint is, along with osteoarthritis of the facet joints, one of the main sources of mechanical low back pain. Here we discuss the negative results of two recent randomized controlled trials in the Netherlands on the use of radiofrequency (RF) denervation to treat low back pain arising from the SI joint. Possible causes of treatment failure are discussed. The authors also discuss the use of an intra-articular injection of the combination of a local anaesthetic and a glucocorticoid as an alternative to RF denervation. PMID- 27378267 TI - [Not Available]. AB - A man with excessive skin lesions. PMID- 27378268 TI - Assessment and improvement of HIV screening rates in a Midwest primary care practice using an electronic clinical decision support system: a quality improvement study. AB - BACKGROUND: Universal human immunodeficiency virus (HIV) screening remains low in many clinical practices despite published guidelines recommending screening for all patients between ages 13-65. Electronic clinical decision support tools have improved screening rates for many chronic diseases. We designed a quality improvement project to improve the rate of universal HIV screening of adult patients in a Midwest primary care practice using a clinical decision support tool. METHODS: We conducted this quality improvement project in Rochester, Minnesota from January 1, 2014 to December 31, 2014. Baseline primary care practice HIV screening data were acquired from January 1, 2014 to April 30, 2014. We surveyed providers and educated them about current CDC recommended screening guidelines. We then added an HIV screening alert to an existing electronic clinical decision support tool and post-intervention HIV screening rates were obtained from May 1, 2014 to December 31, 2014. The primary quality outcome being assessed was change in universal HIV screening rates. RESULTS: Twelve thousand five hundred ninety-six unique patients were eligible for HIV screening in 2014; 327 were screened for HIV. 6,070 and 6,526 patients were seen before and after the intervention, respectively. 1.80 % of eligible patients and 3.34 % of eligible patients were screened prior to and after the intervention, respectively (difference of -1.54 % [-2.1 %, -0.99 %], p < 0.0001); OR 1.89 (1.50, 2.38). Prior to the intervention, African Americans were more likely to have been screened for HIV (OR 3.86 (2.22, 6.71; p < 0.001) than Whites, but this effect decreased significantly after the intervention (OR 1.90 (1.12, 3.21; p = 0.03). CONCLUSIONS: These data showed that an electronic alert almost doubled the rates of universal HIV screening by primary care providers in a Midwestern practice and reduced racial disparities, but there is still substantial room for improvement in universal screening practices. Opportunities for universal HIV screening remain abundant, as many providers either do not understand the importance of screening average risk patients or do not remember to discuss it. Alerts to remind providers of current guidelines and help identify screening opportunities can be helpful. PMID- 27378270 TI - Molecular chaperone accumulation as a function of stress evidences adaptation to high hydrostatic pressure in the piezophilic archaeon Thermococcus barophilus. AB - The accumulation of mannosyl-glycerate (MG), the salinity stress response osmolyte of Thermococcales, was investigated as a function of hydrostatic pressure in Thermococcus barophilus strain MP, a hyperthermophilic, piezophilic archaeon isolated from the Snake Pit site (MAR), which grows optimally at 40 MPa. Strain MP accumulated MG primarily in response to salinity stress, but in contrast to other Thermococcales, MG was also accumulated in response to thermal stress. MG accumulation peaked for combined stresses. The accumulation of MG was drastically increased under sub-optimal hydrostatic pressure conditions, demonstrating that low pressure is perceived as a stress in this piezophile, and that the proteome of T. barophilus is low-pressure sensitive. MG accumulation was strongly reduced under supra-optimal pressure conditions clearly demonstrating the structural adaptation of this proteome to high hydrostatic pressure. The lack of MG synthesis only slightly altered the growth characteristics of two different MG synthesis deletion mutants. No shift to other osmolytes was observed. Altogether our observations suggest that the salinity stress response in T. barophilus is not essential and may be under negative selective pressure, similarly to what has been observed for its thermal stress response. PMID- 27378269 TI - Systematic drug screening reveals specific vulnerabilities and co-resistance patterns in endocrine-resistant breast cancer. AB - BACKGROUND: The estrogen receptor (ER) inhibitor tamoxifen reduces breast cancer mortality by 31 % and has served as the standard treatment for ER-positive breast cancers for decades. However, 50 % of advanced ER-positive cancers display de novo resistance to tamoxifen, and acquired resistance evolves in 40 % of patients who initially respond. Mechanisms underlying resistance development remain poorly understood and new therapeutic opportunities are urgently needed. Here, we report the generation and characterization of seven tamoxifen-resistant breast cancer cell lines from four parental strains. METHODS: Using high throughput drug sensitivity and resistance testing (DSRT) with 279 approved and investigational oncology drugs, exome-sequencing and network analysis, we for the first time, systematically determine the drug response profiles specific to tamoxifen resistance. RESULTS: We discovered emerging vulnerabilities towards specific drugs, such as ERK1/2-, proteasome- and BCL-family inhibitors as the cells became tamoxifen-resistant. Co-resistance to other drugs such as the survivin inhibitor YM155 and the chemotherapeutic agent paclitaxel also occurred. CONCLUSION: This study indicates that multiple molecular mechanisms dictate endocrine resistance, resulting in unexpected vulnerabilities to initially ineffective drugs, as well as in emerging co-resistances. Thus, combatting drug-resistant tumors will require patient-tailored strategies in order to identify new drug vulnerabilities, and to understand the associated co-resistance patterns. PMID- 27378271 TI - Gate dependence of upper critical field in superconducting (110) LaAlO3/SrTiO3 interface. AB - The fundamental parameters of the superconducting state such as coherence length and pairing strength are essential for understanding the nature of superconductivity. These parameters can be estimated by measuring critical parameters such as upper critical field, Hc2. In this work, Hc2 of a superconducting (110) LaAlO3/SrTiO3 interface is determined through magnetoresistive measurements as a function of the gate voltage, VG. When VG increases, the critical temperature has a dome-like shape, while Hc2 monotonically decreases. This relationship of independence between the variation of Tc and of Hc2 suggests that the Cooper pairing potential is stronger in the underdoped region and the coherence length increases with the increase of VG. The result is as for high temperature superconducting cuprates and it is different than for conventional low temperature superconductors. PMID- 27378272 TI - Metabolic Control in Older Dependent People: Need for Improvement? PMID- 27378273 TI - Reply to Letter to the Editor by R.L. Jump et al. PMID- 27378274 TI - Treatment of Stroke in Canadian Emergency Departments: Time to be Leaders. PMID- 27378275 TI - The prevalence of food allergy and epinephrine auto-injectors in Dutch food allergic adolescents. PMID- 27378277 TI - Efficient Route to Deuterated Aromatics by the Deamination of Anilines. AB - One-step replacement of NH2 groups in ring-substituted anilines by deuterium is reported. Approaches comprising both solid-phase and solution-phase syntheses can be used on a large variety of substrates. The method uses diazotization in a mixture of water and either dichloromethane or chloroform, which serve as a source of hydrogen. This protocol can be used as a general method for fast and easy incorporation of deuterium into an aromatic system using deuterated chloroform. PMID- 27378276 TI - Recombinant human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) produced in the methylotrophic yeast Pichia pastoris. AB - Mucopolysaccharidosis IV A (MPS IV A, Morquio A disease) is a lysosomal storage disease (LSD) produced by mutations on N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Recently an enzyme replacement therapy (ERT) for this disease was approved using a recombinant enzyme produced in CHO cells. Previously, we reported the production of an active GALNS enzyme in Escherichia coli that showed similar stability properties to that of a recombinant mammalian enzyme though it was not taken-up by culture cells. In this study, we showed the production of the human recombinant GALNS in the methylotrophic yeast Pichia pastoris GS115 (prGALNS). We observed that removal of native signal peptide and co-expression with human formylglycine-generating enzyme (SUMF1) allowed an improvement of 4.5 fold in the specific GALNS activity. prGALNS enzyme showed a high stability at 4 degrees C, while the activity was markedly reduced at 37 and 45 degrees C. It was noteworthy that prGALNS was taken-up by HEK293 cells and human skin fibroblasts in a dose-dependent manner through a process potentially mediated by an endocytic pathway, without any additional protein or host modification. The results show the potential of P. pastoris in the production of a human recombinant GALNS for the development of an ERT for Morquio A. PMID- 27378278 TI - The effect of cilostazol on electrophysiologic changes in non-proliferative diabetic retinopathy patients. AB - PURPOSE: To evaluate the effects of cilostazol, an antiplatelet and vasodilation agent, on the retinal function of patients with non-proliferative diabetic retinopathy (NPDR) using a full-field electroretinogram (ffERG). METHODS: A total of 20 eyes from 20 patients were enrolled as the cilostazol-treated group, and 16 eyes from 16 patients were enrolled as the control group to assess the functional effects of cilostazol. Ophthalmologic examinations including fundus fluorescein angiography (FFA), fundus color photography, optical coherence tomography (OCT), and ffERG responses were recorded at baseline and after 1 year of cilostazol treatment. The number of microaneurysms on FFA, the number of exudates on fundus photographs, and central macular thickness (CMT) on OCT were compared between the two groups. Recording of ffERG was also performed at baseline and repeated after 1 year of treatment. The mean implicit times and amplitudes of a- and b-waves in each ffERG response were analyzed to evaluate the retinal function. RESULTS: CMT and the numbers of microaneurysms and exudates showed no significant change in the cilostazol-treated group. There was no significant change in ffERG parameters between baseline and 1 year after the treatment in each group. The mean changes in implicit times from the cilostazol-treated group were significantly less than in the control group in b-waves from dark-adapted 3 ERG (p = 0.017) and 10 ERG responses (p = 0.047). On the other hand, the mean changes in amplitudes were not significant after 1 year of cilostazol treatment, but there were slight increases in amplitudes of dark-adapted 0.01 ERG and 10 ERG in the cilostazol-treated group. CONCLUSIONS: These results suggest that cilostazol administration could reduce the implicit times of ffERG in patients with NPDR. It may be beneficial to preserve the retinal function in the diabetic retina, and additional research with larger populations and extended duration are needed to clarify the efficacy and safety of cilostazol for these patients. PMID- 27378279 TI - The effect of early life status epilepticus on ultrasonic vocalizations in mice. AB - OBJECTIVE: Infant crying is a series of innate vocal patterns intended to elicit the attention of adult caregivers for fulfillment of specific needs such as pain, hunger, or hypostimulation. It is one of the earliest forms of observable communication. In neonatal rodents, this behavior has recently been investigated as a potential early behavioral marker of neural deficits in neurodevelopmental disorders. However, few studies have examined the effects of seizures on vocalization behavior during the neonatal period. The purpose of this study is to investigate the effect of a single kainate-induced early life seizure on vocalization behavior in mice. This study also investigates the subsequent effect of seizures on two pathways critical for early neural development and epileptogenesis: the phosphoinositide 3-kinase|serine/threonine kinase|mammalian target of rapamycin (PI3K-Akt-mTOR) and canonical (Wingless-Int Wnt) intracellular signaling pathways. METHODS: On postnatal day 10, male and female 129SvEvTac mice received a single intraperitoneal injection of kainic acid (2.5 mg/kg) or vehicle injection. The kainate administration resulted in 1-2 h of status epilepticus. On postnatal days 11 and 12, the quantity and duration of isolation-induced ultrasonic vocalizations were recorded. Western blotting analyses were performed using male and female pups on postnatal day 12. RESULTS: There was significant, male-specific suppression in the quantity and total duration of 50-kHz calls on postnatal day 12 following seizures. The hippocampi of male mice on this postnatal day also revealed male-specific changes in the PI3K-Akt-mTOR intracellular signaling pathway, as well as changes in phosphorylated fragile * mental retardation protein. SIGNIFICANCE: These findings demonstrate that early life seizures can disrupt communication behavior in neonatal mice. PMID- 27378280 TI - Climate-based statistical regression models for crop yield forecasting of coffee in humid tropical Kerala, India. AB - A study on the variability of coffee yield of both Coffea arabica and Coffea canephora as influenced by climate parameters (rainfall (RF), maximum temperature (Tmax), minimum temperature (Tmin), and mean relative humidity (RH)) was undertaken at Regional Coffee Research Station, Chundale, Wayanad, Kerala State, India. The result on the coffee yield data of 30 years (1980 to 2009) revealed that the yield of coffee is fluctuating with the variations in climatic parameters. Among the species, productivity was higher for C. canephora coffee than C. arabica in most of the years. Maximum yield of C. canephora (2040 kg ha 1) was recorded in 2003-2004 and there was declining trend of yield noticed in the recent years. Similarly, the maximum yield of C. arabica (1745 kg ha-1) was recorded in 1988-1989 and decreased yield was noticed in the subsequent years till 1997-1998 due to year to year variability in climate. The highest correlation coefficient was found between the yield of C. arabica coffee and maximum temperature during January (0.7) and between C. arabica coffee yield and RH during July (0.4). Yield of C. canephora coffee had highest correlation with maximum temperature, RH and rainfall during February. Statistical regression model between selected climatic parameters and yield of C. arabica and C. canephora coffee was developed to forecast the yield of coffee in Wayanad district in Kerala. The model was validated for years 2010, 2011, and 2012 with the coffee yield data obtained during the years and the prediction was found to be good. PMID- 27378281 TI - Evaluating of simulated carbon flux phenology over a cropland ecosystem in a semiarid area of China with SiBcrop. AB - The cropland ecosystem in semiarid areas is sensitive to climate change. The accurate representation of crop phenology is important for predicting the carbon and water exchange process. The performance of a newly developed phenological model (SiBcrop) for simulations of carbon flux phenology in a semiarid area ecosystem was evaluated. The results showed that the SiBcrop improved the prediction for daily maximum gross primary production (GPP), and the days GPP reached the maximum value were closer to the observation, compared to SiB3. SiBcrop had a better prediction for both monthly total net ecosystem exchange (NEE) in the growing season than in the dormant season in semiarid areas. The day when the cumulative NEE predicted with SiBcrop became positive was closer to the observation. The observed start date of carbon uptake (CUstart) had a larger annual variation than did the end date of carbon uptake (CUend). SiBcrop had a better prediction for CUstart but poor for CUend, compared to SiB3. There was a longer carbon uptake period (CUP) predicted with SiBcrop than the observed results. PMID- 27378282 TI - Environmental controls of evapotranspiration in a mixed plantation in North China. AB - The mixed plantation plays an important role in the water cycle in the hilly area of North China. To evaluate the effect of afforestation on the water balance in this region, the temporal variation of evapotranspiration (ET) and environmental controls were investigated based on the eddy flux measurement of water vapor in a 31-year-old mixed plantation from 2006 to 2010. During 5 years, annual ET ranged from 513 to 680 mm, with an average of 579 mm. Growing season ET accounted for 72 82 % of annual ET during the 5-year period and its interannual variation was determined by the number of rainy days. In the non-growing and growing seasons, monthly ET was primarily dependent on monthly mean soil water content and monthly mean net radiation, respectively. Annual mean Priestley-Taylor coefficient (alpha) was 0.64, and the decoupling factor (Omega) was 0.48. High values of alpha and Omega implied that ET was energy limited in the growing seasons of 2006 2010. The mean annual ratio of ET to precipitation (ET/P) was 1.10. The density of the mixed plantation was around 50 % higher than the optimal value determined by local water capacity, leading to a large ET/P ratio. The dense plantation needs to be thinned to prevent excessive water loss in the hilly area of North China. PMID- 27378283 TI - Engineering biosynthesis of the anticancer alkaloid noscapine in yeast. AB - Noscapine is a potential anticancer drug isolated from the opium poppy Papaver somniferum, and genes encoding enzymes responsible for the synthesis of noscapine have been recently discovered to be clustered on the genome of P. somniferum. Here, we reconstitute the noscapine gene cluster in Saccharomyces cerevisiae to achieve the microbial production of noscapine and related pathway intermediates, complementing and extending previous in planta and in vitro investigations. Our work provides structural validation of the secoberberine intermediates and the description of the narcotoline-4'-O-methyltransferase, suggesting this activity is catalysed by a unique heterodimer. We also reconstitute a 14-step biosynthetic pathway of noscapine from the simple alkaloid norlaudanosoline by engineering a yeast strain expressing 16 heterologous plant enzymes, achieving reconstitution of a complex plant pathway in a microbial host. Other engineered yeasts produce previously inaccessible pathway intermediates and a novel derivative, thereby advancing protoberberine and noscapine related drug discovery. PMID- 27378284 TI - Constructing thioether-tethered cyclic peptides via on-resin intra-molecular thiol-ene reaction. AB - Thiol-ene reactions have been used in a variety of applications that mostly involve an inter-molecular pathway. Herein, we report a facile method to construct thioether-tethered cyclic peptides via an intra-molecular thiol-ene reaction. This reaction is efficient, selective, and has good residue compatibility. Short peptides with thioether tethers were constructed and were used to construct longer cyclic peptides. This synthetic method may be useful for constructing bioactive peptides. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 27378285 TI - Degradation and protection of DNAzymes on human skin. AB - DNAzymes are catalytic nucleic acid based molecules that have become a new class of active pharmaceutical ingredients (API). Until now, five DNAzymes have entered clinical trials. Two of them were tested for topical application, whereby dermally applied DNAzymes had been prone to enzymatic degradation. To protect the DNAzymes the enzymatic activity of human skin has to be examined. Therefore, the enzymatic activity of human skin was qualitatively and quantitatively analyzed. Activity similar to that of DNase II could be identified and the specific activity was determined to be 0.59Units/mg. These results were used to develop an in vitro degradation assay to screen different kinds of protective systems on human skin. The chosen protective systems consisted of biodegradable chitosans or polyethylenimine, which forms polyplexes when combined with DNAzymes. The polyplexes were characterized in terms of particle size, zeta potential, stability and degree of complexation. The screening revealed that the protective efficiency of the polyplexes depended on the polycation and the charge ratio (xi). At a critical xi ratio between 1.0 and 4.1 and at a maximal zeta potential, sufficient protection of the DNAzyme was achieved. The results of this study will be helpful for the development of a protective dermal drug delivery systems using polyplexes. PMID- 27378286 TI - A nanoformulation containing a scFv reactive to electronegative LDL inhibits atherosclerosis in LDL receptor knockout mice. AB - Atherosclerosis is a chronic inflammatory disease responsible for the majority of cases of myocardial infarction and ischemic stroke. The electronegative low density lipoprotein, a modified subfraction of native LDL, is pro-inflammatory and plays an important role in atherogenesis. To investigate the effects of a nanoformulation (scFv anti-LDL(-)-MCMN-Zn) containing a scFv reactive to LDL(-) on the inhibition of atherosclerosis, its toxicity was evaluated in vitro and in vivo and further it was also administered weekly to LDL receptor knockout mice. The scFv anti-LDL(-)-MCMN-Zn nanoformulation did not induce cell death in RAW 264.7 macrophages and HUVECs. The 5mg/kg dose of scFv anti-LDL(-)-MCMN-Zn did not cause any typical signs of toxicity and it was chosen for the evaluation of its atheroprotective effect in Ldlr(-/-) mice. This nanoformulation significantly decreased the atherosclerotic lesion area at the aortic sinus, compared with that in untreated mice. In addition, the Il1b mRNA expression and CD14 protein expression were downregulated in the atherosclerotic lesions at the aortic arch of Ldlr(-/-) mice treated with scFv anti-LDL(-)-MCMN-Zn. Thus, the scFv anti-LDL( )-MCMN-Zn nanoformulation inhibited the progression of atherosclerotic lesions, indicating its potential use in a future therapeutic strategy for atherosclerosis. PMID- 27378287 TI - Theoretical and experimental investigation of drug-polymer interaction and miscibility and its impact on drug supersaturation in aqueous medium. AB - Amorphous solid dispersions (ASDs) have the potential to offer higher apparent solubility and bioavailability of BCS class II drugs. Knowledge of the solid state drug-polymer solubility/miscibility and their mutual interaction are fundamental requirements for the effective design and development of such systems. To this end, we have carried out a comprehensive investigation of various ASD systems of dipyridamole and cinnarizine in polyvinylpyrrolidone (PVP) and polyacrylic acid (PAA) at different drug loadings. Theoretical and experimental examinations (by implementing binary and ternary Flory-Huggins (F-H) theory) related to drug-polymer interaction/miscibility including solubility parameter approach, melting point depression method, phase diagram, drug-polymer interaction in the presence of moisture and the effect of drug loading on interaction parameter were performed. The information obtained from this study was used to predict the stability of ASDs at different drug loadings and under different thermal and moisture conditions. Thermal and moisture sorption analysis not only provided the composition-dependent interaction parameter but also predicted the composition dependent miscibility. DPM-PVP, DPM-PAA and CNZ-PAA systems have shown molecular level mixing over the complete range of drug loading. For CNZ-PVP, the presence of a single Tg at lower drug loadings (10, 20 and 35%w/w) indicates the formation of solid solution. However, drug recrystallization was observed for samples with higher drug weight fractions (50 and 65%w/w). Finally, the role of polymer in maintaining drug supersaturation has also been explored. It has been found that drug-polymer combinations capable of hydrogen-bonding in the solution state (DPM-PVP, DPM-PAA and CNZ-PAA) are more effective in preventing drug crystallization compared to the drug-polymer systems without such interaction (CNZ-PVP). The DPM-PAA system outperformed all other ASDs in various stability conditions (dry-state, in the presence of moisture and in solution state), which was attributed to the drug's low crystallization tendency, the strong DPM-PAA interaction, the robustness of this interaction against moisture or water and the ability of PAA in maintaining DPM supersaturation. PMID- 27378288 TI - AMIGO2, a toolbox for dynamic modeling, optimization and control in systems biology. AB - MOTIVATION: Many problems of interest in dynamic modeling and control of biological systems can be posed as non-linear optimization problems subject to algebraic and dynamic constraints. In the context of modeling, this is the case of, e.g. parameter estimation, optimal experimental design and dynamic flux balance analysis. In the context of control, model-based metabolic engineering or drug dose optimization problems can be formulated as (multi-objective) optimal control problems. Finding a solution to those problems is a very challenging task which requires advanced numerical methods. RESULTS: This work presents the AMIGO2 toolbox: the first multiplatform software tool that automatizes the solution of all those problems, offering a suite of state-of-the-art (multi-objective) global optimizers and advanced simulation approaches. AVAILABILITY AND IMPLEMENTATION: The toolbox and its documentation are available at: sites.google.com/site/amigo2toolbox CONTACT: ebalsa@iim.csic.esSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27378289 TI - w4CSeq: software and web application to analyze 4C-seq data. AB - : Circularized Chromosome Conformation Capture followed by deep sequencing (4C Seq) is a powerful technique to identify genome-wide partners interacting with a pre-specified genomic locus. Here, we present a computational and statistical approach to analyze 4C-Seq data generated from both enzyme digestion and sonication fragmentation-based methods. We implemented a command line software tool and a web interface called w4CSeq, which takes in the raw 4C sequencing data (FASTQ files) as input, performs automated statistical analysis and presents results in a user-friendly manner. Besides providing users with the list of candidate interacting sites/regions, w4CSeq generates figures showing genome-wide distribution of interacting regions, and sketches the enrichment of key features such as TSSs, TTSs, CpG sites and DNA replication timing around 4C sites. AVAILABILITY AND IMPLEMENTATION: Users can establish their own web server by downloading source codes at https://github.com/WGLab/w4CSeq Additionally, a demo web server is available at http://w4cseq.wglab.org CONTACT: kaiwang@usc.edu or wangelu@usc.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27378290 TI - TwoPhaseInd: an R package for estimating gene-treatment interactions and discovering predictive markers in randomized clinical trials. AB - : In randomized clinical trials, identifying baseline genetic or genomic markers for predicting subgroup treatment effects is of rising interest. Outcome dependent sampling is often employed for measuring markers. The R package TwoPhaseInd implements a number of efficient statistical methods we developed for estimating subgroup treatment effects and gene-treatment interactions, exploiting the gene-treatment independence dictated by randomization, including the case only estimator, the maximum estimated likelihood estimator and the semiparametric maximum likelihood estimator for parameters in a logistic model. For rare failure events subject to censoring, we have proposed efficient augmented case-only designs, a variation of the case-cohort design, to estimate genetic associations and subgroup treatment effects in a Cox regression model. The R package is computationally scalable to genome-wide studies, as illustrated by an example from Women's Health Initiative. AVAILABILITY AND IMPLEMENTATION: The R package TwoPhaseInd is available from http://cran.r-project.org/web/packages CONTACT: jdai@fredhutch.org. PMID- 27378291 TI - SwiSpot: modeling riboswitches by spotting out switching sequences. AB - MOTIVATION: Riboswitches are cis-regulatory elements in mRNA, mostly found in Bacteria, which exhibit two main secondary structure conformations. Although one of them prevents the gene from being expressed, the other conformation allows its expression, and this switching process is typically driven by the presence of a specific ligand. Although there are a handful of known riboswitches, our knowledge in this field has been greatly limited due to our inability to identify their alternate structures from their sequences. Indeed, current methods are not able to predict the presence of the two functionally distinct conformations just from the knowledge of the plain RNA nucleotide sequence. Whether this would be possible, for which cases, and what prediction accuracy can be achieved, are currently open questions. RESULTS: Here we show that the two alternate secondary structures of riboswitches can be accurately predicted once the 'switching sequence' of the riboswitch has been properly identified. The proposed SwiSpot approach is capable of identifying the switching sequence inside a putative, complete riboswitch sequence, on the basis of pairing behaviors, which are evaluated on proper sets of configurations. Moreover, it is able to model the switching behavior of riboswitches whose generated ensemble covers both alternate configurations. Beyond structural predictions, the approach can also be paired to homology-based riboswitch searches. AVAILABILITY AND IMPLEMENTATION: SwiSpot software, along with the reference dataset files, is available at: http://www.iet.unipi.it/a.bechini/swispot/Supplementary information: Supplementary data are available at Bioinformatics online. CONTACT: a.bechini@ing.unipi.it. PMID- 27378292 TI - ConsPred: a rule-based (re-)annotation framework for prokaryotic genomes. AB - MOTIVATION: The rapidly growing number of available prokaryotic genome sequences requires fully automated and high-quality software solutions for their initial and re-annotation. Here we present ConsPred, a prokaryotic genome annotation framework that performs intrinsic gene predictions, homology searches, predictions of non-coding genes as well as CRISPR repeats and integrates all evidence into a consensus annotation. ConsPred achieves comprehensive, high quality annotations based on rules and priorities, similar to decision-making in manual curation and avoids conflicting predictions. Parameters controlling the annotation process are configurable by the user. ConsPred has been used in the institutions of the authors for longer than 5 years and can easily be extended and adapted to specific needs. SUMMARY: The ConsPred algorithm for producing a consensus from the varying scores of multiple gene prediction programs approaches manual curation in accuracy. Its rule-based approach for choosing final predictions avoids overriding previous manual curations. AVAILABILITY AND IMPLEMENTATION: ConsPred is implemented in Java, Perl and Shell and is freely available under the Creative Commons license as a stand-alone in-house pipeline or as an Amazon Machine Image for cloud computing, see https://sourceforge.net/projects/conspred/. CONTACT: thomas.rattei@univie.ac.atSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27378293 TI - MetaPred2CS: a sequence-based meta-predictor for protein-protein interactions of prokaryotic two-component system proteins. AB - MOTIVATION: Two-component systems (TCS) are the main signalling pathways of prokaryotes, and control a wide range of biological phenomena. Their functioning depends on interactions between TCS proteins, the specificity of which is poorly understood. RESULTS: The MetaPred2CS web-server interfaces a sequence-based meta predictor specifically designed to predict pairing of the histidine kinase and response-regulator proteins forming TCSs. MetaPred2CS integrates six sequence based methods using a support vector machine classifier and has been intensively tested under different benchmarking conditions: (i) species specific gene sets; (ii) neighbouring versus orphan pairs; and (iii) k-fold cross validation on experimentally validated datasets. AVAILABILITY AND IMPLEMENTATION: Web server at: http://metapred2cs.ibers.aber.ac.uk/, Source code: https://github.com/martinjvickers/MetaPred2CS or implemented as Virtual Machine at: http://metapred2cs.ibers.aber.ac.uk/download CONTACT: naf4@aber.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27378294 TI - ChAsE: chromatin analysis and exploration tool. AB - : : We present ChAsE, a cross-platform desktop application developed for interactive visualization, exploration and clustering of epigenomic data such as ChIP-seq experiments. ChAsE is designed and developed in close collaboration with several groups of biologists and bioinformaticians with a focus on usability and interactivity. Data can be analyzed through k-means clustering, specifying presence or absence of signal in epigenetic data and performing set operations between clusters. Results can be explored in an interactive heat map and profile plot interface and exported for downstream analysis or as high quality figures suitable for publications. AVAILABILITY AND IMPLEMENTATION: Software, source code (MIT License), data and video tutorials available at http://chase.cs.univie.ac.at CONTACT: : mkarimi@brc.ubc.ca or torsten.moeller@univie.ac.atSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27378295 TI - Unbiased classification of spatial strategies in the Barnes maze. AB - MOTIVATION: Spatial learning is one of the most widely studied cognitive domains in neuroscience. The Morris water maze and the Barnes maze are the most commonly used techniques to assess spatial learning and memory in rodents. Despite the fact that these tasks are well-validated paradigms for testing spatial learning abilities, manual categorization of performance into behavioral strategies is subject to individual interpretation, and thus to bias. We have previously described an unbiased machine-learning algorithm to classify spatial strategies in the Morris water maze. RESULTS: Here, we offer a support vector machine-based, automated, Barnes-maze unbiased strategy (BUNS) classification algorithm, as well as a cognitive score scale that can be used for memory acquisition, reversal training and probe trials. The BUNS algorithm can greatly benefit Barnes maze users as it provides a standardized method of strategy classification and cognitive scoring scale, which cannot be derived from typical Barnes maze data analysis. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at http://okunlab.wix.com/okunlab as a MATLAB application. CONTACT: eitan.okun@biu.ac.ilSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27378296 TI - Application of the MAFFT sequence alignment program to large data-reexamination of the usefulness of chained guide trees. AB - MOTIVATION: Large multiple sequence alignments (MSAs), consisting of thousands of sequences, are becoming more and more common, due to advances in sequencing technologies. The MAFFT MSA program has several options for building large MSAs, but their performances have not been sufficiently assessed yet, because realistic benchmarking of large MSAs has been difficult. Recently, such assessments have been made possible through the HomFam and ContTest benchmark protein datasets. Along with the development of these datasets, an interesting theory was proposed: chained guide trees increase the accuracy of MSAs of structurally conserved regions. This theory challenges the basis of progressive alignment methods and needs to be examined by being compared with other known methods including computationally intensive ones. RESULTS: We used HomFam, ContTest and OXFam (an extended version of OXBench) to evaluate several methods enabled in MAFFT: (1) a progressive method with approximate guide trees, (2) a progressive method with chained guide trees, (3) a combination of an iterative refinement method and a progressive method and (4) a less approximate progressive method that uses a rigorous guide tree and consistency score. Other programs, Clustal Omega and UPP, available for large MSAs, were also included into the comparison. The effect of method 2 (chained guide trees) was positive in ContTest but negative in HomFam and OXFam. Methods 3 and 4 increased the benchmark scores more consistently than method 2 for the three datasets, suggesting that they are safer to use. AVAILABILITY AND IMPLEMENTATION: http://mafft.cbrc.jp/alignment/software/ CONTACT: katoh@ifrec.osaka-u.ac.jpSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27378297 TI - The SMAL web server: global multiple network alignment from pairwise alignments. AB - MOTIVATION: Alignments of protein-protein interaction networks (PPIN) can be used to predict protein function, study conserved aspects of the interactome, and to establish evolutionary correspondences. Within this problem context, determining multiple network alignments (MNA) is a significant challenge that involves high computational complexity. A limited number of public MNA implementations are available currently and the majority of the pairwise network alignment (PNA) algorithms do not have MNA counterparts. Furthermore, current MNA algorithms do not allow choosing a specific PPIN relative to which an MNA could be constructed. Also, once an MNA is obtained, it cannot easily be modified, such as through addition of a new network, without expensive re-computation of the entire MNA. RESULTS: SMAL (Scaffold-Based Multiple Network Aligner) is a public, open-source, web-based application for determining MNAs from existing PNAs that addresses all the aforementioned challenges. With SMAL, PNAs can be combined rapidly to obtain an MNA. The software also supports visualization and user-data interactions to facilitate exploratory analysis and sensemaking. SMAL is especially useful when multiple alignments relative to a particular PPIN are required; furthermore, SMAL alignments are persistent in that existing correspondences between networks (obtained during PNA or MNA) are not lost as new networks are added. In comparative studies alongside existent MNA techniques, SMAL MNAs were found to be superior per a number of measures, such as the total number of identified homologs and interologs as well as the fraction of all identified correspondences that are functionally similar or homologous to the scaffold. While directed primarily at PPIN-alignment, SMAL is a generic network aligner and may be applied to arbitrary networks.Availability information: The SMAL web server and source code is available at: http://haddock6.sfsu.edu/smal/ CONTACT: rahul@sfsu.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27378299 TI - Icarus: visualizer for de novo assembly evaluation. AB - : : Data visualization plays an increasingly important role in NGS data analysis. With advances in both sequencing and computational technologies, it has become a new bottleneck in genomics studies. Indeed, evaluation of de novo genome assemblies is one of the areas that can benefit from the visualization. However, even though multiple quality assessment methods are now available, existing visualization tools are hardly suitable for this purpose. Here, we present Icarus a novel genome visualizer for accurate assessment and analysis of genomic draft assemblies, which is based on the tool QUAST. Icarus can be used in studies where a related reference genome is available, as well as for non-model organisms. The tool is available online and as a standalone application. AVAILABILITY AND IMPLEMENTATION: http://cab.spbu.ru/software/icarus CONTACT: aleksey.gurevich@spbu.ruSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27378298 TI - Performance of protein-structure predictions with the physics-based UNRES force field in CASP11. AB - : Participating as the Cornell-Gdansk group, we have used our physics-based coarse-grained UNited RESidue (UNRES) force field to predict protein structure in the 11th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP11). Our methodology involved extensive multiplexed replica exchange simulations of the target proteins with a recently improved UNRES force field to provide better reproductions of the local structures of polypeptide chains. All simulations were started from fully extended polypeptide chains, and no external information was included in the simulation process except for weak restraints on secondary structure to enable us to finish each prediction within the allowed 3-week time window. Because of simplified UNRES representation of polypeptide chains, use of enhanced sampling methods, code optimization and parallelization and sufficient computational resources, we were able to treat, for the first time, all 55 human prediction targets with sizes from 44 to 595 amino acid residues, the average size being 251 residues. Complete structures of six single-domain proteins were predicted accurately, with the highest accuracy being attained for the T0769, for which the CalphaRMSD was 3.8 A for 97 residues of the experimental structure. Correct structures were also predicted for 13 domains of multi-domain proteins with accuracy comparable to that of the best template-based modeling methods. With further improvements of the UNRES force field that are now underway, our physics based coarse-grained approach to protein-structure prediction will eventually reach global prediction capacity and, consequently, reliability in simulating protein structure and dynamics that are important in biochemical processes. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at http://www.unres.pl/ CONTACT: has5@cornell.edu. PMID- 27378300 TI - An empirical Bayes method for genotyping and SNP detection using multi-sample next-generation sequencing data. AB - MOTIVATION: The development of next generation sequencing technology provides an efficient and powerful approach to rare variant detection. To identify genetic variations, the essential question is how to quantity the sequencing error rate in the data. Because of the advantage of easy implementation and the ability to integrate data from different sources, the empirical Bayes method is popularly employed to estimate the sequencing error rate for SNP detection. RESULTS: We propose a novel statistical model to fit the observed non-reference allele frequency data, and utilize the empirical Bayes method for both genotyping and SNP detection, where an ECM algorithm is implemented to estimate the model parameters. The performance of our proposed method is investigated via simulations and real data analysis. It is shown that our method makes less genotype-call errors, and with the parameter estimates from the ECM algorithm, it attains high detection power with FDR being well controlled. AVAILABILITY AND IMPLEMENTATION: The proposed algorithm is wrapped in the R package ebGenotyping, which can be downloaded from http://cran.r-project.org/web/packages/ebGenotyping/ CONTACT: youn@mail.sysu.edu.cnSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27378301 TI - Recognizing metal and acid radical ion-binding sites by integrating ab initio modeling with template-based transferals. AB - MOTIVATION: More than half of proteins require binding of metal and acid radical ions for their structure and function. Identification of the ion-binding locations is important for understanding the biological functions of proteins. Due to the small size and high versatility of the metal and acid radical ions, however, computational prediction of their binding sites remains difficult. RESULTS: We proposed a new ligand-specific approach devoted to the binding site prediction of 13 metal ions (Zn2+, Cu2+, Fe2+, Fe3+, Ca2+, Mg2+, Mn2+, Na+, K+) and acid radical ion ligands (CO32-, NO2-, SO42-, PO43-) that are most frequently seen in protein databases. A sequence-based ab initio model is first trained on sequence profiles, where a modified AdaBoost algorithm is extended to balance binding and non-binding residue samples. A composite method IonCom is then developed to combine the ab initio model with multiple threading alignments for further improving the robustness of the binding site predictions. The pipeline was tested using 5-fold cross validations on a comprehensive set of 2,100 non redundant proteins bound with 3,075 small ion ligands. Significant advantage was demonstrated compared with the state of the art ligand-binding methods including COACH and TargetS for high-accuracy ion-binding site identification. Detailed data analyses show that the major advantage of IonCom lies at the integration of complementary ab initio and template-based components. Ion-specific feature design and binding library selection also contribute to the improvement of small ion ligand binding predictions. AVAILABILITY AND IMPLEMENTATION: http://zhanglab.ccmb.med.umich.edu/IonCom CONTACT: hxz@imut.edu.cn or zhng@umich.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27378302 TI - Heat*seq: an interactive web tool for high-throughput sequencing experiment comparison with public data. AB - : Better protocols and decreasing costs have made high-throughput sequencing experiments now accessible even to small experimental laboratories. However, comparing one or few experiments generated by an individual lab to the vast amount of relevant data freely available in the public domain might be limited due to lack of bioinformatics expertise. Though several tools, including genome browsers, allow such comparison at a single gene level, they do not provide a genome-wide view. We developed Heat*seq, a web-tool that allows genome scale comparison of high throughput experiments chromatin immuno-precipitation followed by sequencing, RNA-sequencing and Cap Analysis of Gene Expression) provided by a user, to the data in the public domain. Heat*seq currently contains over 12 000 experiments across diverse tissues and cell types in human, mouse and drosophila. Heat*seq displays interactive correlation heatmaps, with an ability to dynamically subset datasets to contextualize user experiments. High quality figures and tables are produced and can be downloaded in multiple formats. AVAILABILITY AND IMPLEMENTATION: Web application: http://www.heatstarseq.roslin.ed.ac.uk/ Source code: https://github.com/gdevailly CONTACT: Guillaume.Devailly@roslin.ed.ac.uk or Anagha.Joshi@roslin.ed.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27378303 TI - deBGA: read alignment with de Bruijn graph-based seed and extension. AB - MOTIVATION: As high-throughput sequencing (HTS) technology becomes ubiquitous and the volume of data continues to rise, HTS read alignment is becoming increasingly rate-limiting, which keeps pressing the development of novel read alignment approaches. Moreover, promising novel applications of HTS technology require aligning reads to multiple genomes instead of a single reference; however, it is still not viable for the state-of-the-art aligners to align large numbers of reads to multiple genomes. RESULTS: We propose de Bruijn Graph-based Aligner (deBGA), an innovative graph-based seed-and-extension algorithm to align HTS reads to a reference genome that is organized and indexed using a de Bruijn graph. With its well-handling of repeats, deBGA is substantially faster than state-of-the-art approaches while maintaining similar or higher sensitivity and accuracy. This makes it particularly well-suited to handle the rapidly growing volumes of sequencing data. Furthermore, it provides a promising solution for aligning reads to multiple genomes and graph-based references in HTS applications. AVAILABILITY AND IMPLEMENTATION: deBGA is available at: https://github.com/hitbc/deBGA CONTACT: ydwang@hit.edu.cnSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27378304 TI - MetaCycle: an integrated R package to evaluate periodicity in large scale data. AB - : Detecting periodicity in large scale data remains a challenge. While efforts have been made to identify best of breed algorithms, relatively little research has gone into integrating these methods in a generalizable method. Here, we present MetaCycle, an R package that incorporates ARSER, JTK_CYCLE and Lomb Scargle to conveniently evaluate periodicity in time-series data. MetaCycle has two functions, meta2d and meta3d, designed to analyze two-dimensional and three dimensional time-series datasets, respectively. Meta2d implements N-version programming concepts using a suite of algorithms and integrating their results. AVAILABILITY AND IMPLEMENTATION: MetaCycle package is available on the CRAN repository (https://cran.r-project.org/web/packages/MetaCycle/index.html) and GitHub (https://github.com/gangwug/MetaCycle). CONTACT: hogenesch@gmail.comSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27378306 TI - Boosting the oxidase mimicking activity of nanoceria by fluoride capping: rivaling protein enzymes and ultrasensitive F(-) detection. AB - Nanomaterial-based enzyme mimics (nanozymes) are currently a new forefront of chemical research. However, the application of nanozymes is limited by their low catalytic activity and low turnover numbers. Cerium dioxide nanoparticles (nanoceria) are among the few with oxidase activity. Herein, we report an interesting finding addressing their limitations. The oxidase activity of nanoceria is improved by over 100-fold by fluoride capping, making it more close to real oxidases. The turnover number reached 700 in 15 min, drastically improved from ~15 turnovers for the naked particles. The mechanism is attributed to surface charge modulation and facilitated electron transfer by F(-) capping based on zeta-potential and free radical measurements. Ultrasensitive sensing of fluoride was achieved with a detection limit of 0.64 MUM F(-) in water and in toothpastes, while no other tested anions can achieve the activity enhancement. PMID- 27378305 TI - LRG1 downregulation in allergic airway disorders and its expression in peripheral blood and tissue cells. AB - BACKGROUND: Increased leucine-rich alpha2-glycoprotein-1 (LRG1) has been observed in plasma of individuals with various diseases. However, the role of LRG1 in allergic airway disease has not been investigated. OBJECTIVE: To explore the involvement of LRG1 in allergy and its cell origins. METHODS: The expression levels of LRG1 and its receptor transforming growth factor-beta receptor II (TGFBR2) in patients with allergic rhinitis (AR) and asthma (AS) were examined by flow cytometry, and enzyme-linked immunosorbent assay (ELISA). RESULTS: LRG1 and soluble TGFBR2 expression in plasma of patients with AR and AS were markedly lower than that of healthy control (HC) subjects. Large proportions of CD123 + HLA-DR-, CD16+, CD4+, CD8+, CD14+, and CD19+ cells expressed LRG1, although the percentages of LRG1+ cells in these cell populations were lower in AR and AS patients. Up to 89.8 and 15.5 % of dispersed mast cells expressed LRG1 and TGFBR2. Moreover, allergen extract exposure significantly reduced LRG1 and TGFBR2 expression in the plasma and leukocytes of patients with AR and AS. CONCLUSIONS: Reduced LRG1 and TGFBR2 levels in patients with allergic airway disorders are likely caused by inhibitory actions of allergens in LRG1 producing cells. Thus, LRG1 may be a key regulatory factor of allergic responses. PMID- 27378307 TI - Glucose-6-phosphate dehydrogenase a novel hope on a blood-based diagnosis of Alzheimer's disease. AB - Alzheimer's disease (AD) is a multi-factorial neurodegenerative disorder that numerous factors have key properties in the development of this proteopathy. Glucose-6-phosphate dehydrogenase (G6PD) is the most common form of enzymopathy. We have examined G6PD enzyme activity levels in the serum of newly diagnosed AD patients compared with control subjects without dementia from the both sexes. Serum G6PD levels were found to be significantly higher (approximately two times) in AD patients compared to control geriatric subjects in both sexes. We have concluded that G6PD seems to play an integral role in the progress and/or prevention of AD. PMID- 27378308 TI - Development and validation of the Simulation Learning Effectiveness Scale for nursing students. AB - AIMS AND OBJECTIVES: To develop and validate the Simulation Learning Effectiveness Scale, which is based on Bandura's social cognitive theory. BACKGROUND: A simulation programme is a significant teaching strategy for nursing students. Nevertheless, there are few evidence-based instruments that validate the effectiveness of simulation learning in Taiwan. DESIGN: This is a quantitative descriptive design. METHODS: In Study 1, a nonprobability convenience sample of 151 student nurses completed the Simulation Learning Effectiveness Scale. Exploratory factor analysis was used to examine the factor structure of the instrument. In Study 2, which involved 365 student nurses, confirmatory factor analysis and structural equation modelling were used to analyse the construct validity of the Simulation Learning Effectiveness Scale. RESULTS: In Study 1, exploratory factor analysis yielded three components: self regulation, self-efficacy and self-motivation. The three factors explained 29.09, 27.74 and 19.32% of the variance, respectively. The final 12-item instrument with the three factors explained 76.15% of variance. Cronbach's alpha was 0.94. In Study 2, confirmatory factor analysis identified a second-order factor termed Simulation Learning Effectiveness Scale. Goodness-of-fit indices showed an acceptable fit overall with the full model (chi2 /df (51) = 3.54, comparative fit index = 0.96, Tucker-Lewis index = 0.95 and standardised root-mean-square residual = 0.035). In addition, teacher's competence was found to encourage learning, and self-reflection and insight were significantly and positively associated with Simulation Learning Effectiveness Scale. Teacher's competence in encouraging learning also was significantly and positively associated with self reflection and insight. Overall, theses variable explained 21.9% of the variance in the student's learning effectiveness. CONCLUSION: The Simulation Learning Effectiveness Scale is a reliable and valid means to assess simulation learning effectiveness for nursing students. RELEVANCE TO CLINICAL PRACTICE: The Simulation Learning Effectiveness Scale can be used to examine nursing students' learning effectiveness and serve as a basis to improve student's learning efficiency through simulation programmes. Future implementation research that focuses on the relationship between learning effectiveness and nursing competence in nursing students is recommended. PMID- 27378309 TI - GBT440 increases haemoglobin oxygen affinity, reduces sickling and prolongs RBC half-life in a murine model of sickle cell disease. AB - A major driver of the pathophysiology of sickle cell disease (SCD) is polymerization of deoxygenated haemoglobin S (HbS), which leads to sickling and destruction of red blood cells (RBCs) and end-organ damage. Pharmacologically increasing the proportion of oxygenated HbS in RBCs may inhibit polymerization, prevent sickling and provide long term disease modification. We report that GBT440, a small molecule which binds to the N-terminal alpha chain of Hb, increases HbS affinity for oxygen, delays in vitro HbS polymerization and prevents sickling of RBCs. Moreover, in a murine model of SCD, GBT440 extends the half-life of RBCs, reduces reticulocyte counts and prevents ex vivo RBC sickling. Importantly, oral dosing of GBT440 in animals demonstrates suitability for once daily dosing in humans and a highly selective partitioning into RBCs, which is a key therapeutic safety attribute. Thus, GBT440 has the potential for clinical use as a disease-modifying agent in sickle cell patients. PMID- 27378310 TI - The lipidation profile of aquaporin-0 correlates with the acyl composition of phosphoethanolamine lipids in lens membranes. AB - The lens fiber major intrinsic protein (otherwise known as aquaporin-0 (AQP0), MIP26 and MP26) has been examined by mass spectrometry (MS) in order to determine the speciation of acyl modifications to the side chains of lysine residues and the N-terminal amino group. The speciation of acyl modifications to the side chain of one specific, highly conserved lysine residue (K238) and the N-terminal amino group of human and bovine AQP0 revealed, in decreasing order of abundance, oleoyl, palmitoyl, stearoyl, eicosenoyl, dihomo-gamma-linolenoyl, palmitoleoyl and eicosadienoyl modifications. In the case of human AQP0, an arachidonoyl modification was also found at the N-terminus. The relative abundances of these modifications mirror the fatty acid composition of lens phosphatidylethanolamine lipids. This lipid class would be expected to be concentrated in the inner leaflet of the lens fiber membrane to which each of the potential AQP0 lipidation sites is proximal. Our data evidence a broad lipidation profile that is both species and site independent, suggesting a chemical-based ester aminolysis mechanism to explain such modifications. PMID- 27378311 TI - SALS-linked WT-SOD1 adopts a highly similar helical conformation as FALS-causing L126Z-SOD1 in a membrane environment. AB - So far >180 mutations have been identified within the 153-residue human SOD1 to cause familial amyotrophic lateral sclerosis (FALS), while wild-type (WT) SOD1 was intriguingly implicated in sporadic ALS (SALS). SOD1 mutations lead to ALS by a dominant gain of cytotoxicity but its mechanism still remains elusive. Previously functional studies have revealed that SOD1 mutants became unexpectedly associated with organelle membranes. Indeed we decoded that the ALS-causing truncation mutant L126Z-SOD1 with an elevated toxicity completely loses the ability to fold into the native beta-barrel structure but acquire a novel capacity to interact with membranes by forming helices over hydrophobic/amphiphilic segments. Very recently, the abnormal insertion of SOD1 mutants into ER membrane has been functionally characterized to trigger ER stress, an initial event of a cascade of cell-specific damages in ALS pathogenesis. Here we attempted to understand the mechanism for gain of cytotoxicity of the WT SOD1. We obtained atomic-resolution evidence that the nascent WT SOD1 without metalation and disulfide bridge is also highly disordered as L126Z. Most importantly, it owns the same capacity in interacting with membranes by forming very similar helices over the first 125 residues identical to L126Z-SOD1, plus an additional hydrophobic helix over Leu144-Ala152. Our study thus implies that the WT and mutant SOD1 indeed converge on a common mechanism for gain of cytotoxicity by abnormally interacting with membranes. Moreover, any genetic/environmental factors which can delay or impair its maturation might act to transform SOD1 into cytotoxic forms with the acquired capacity to abnormally interact with membranes. PMID- 27378312 TI - Two weeks of watermelon juice supplementation improves nitric oxide bioavailability but not endurance exercise performance in humans. AB - This study tested the hypothesis that watermelon juice supplementation would improve nitric oxide bioavailability and exercise performance. Eight healthy recreationally-active adult males reported to the laboratory on two occasions for initial testing without dietary supplementation (control condition). Thereafter, participants were randomly assigned, in a cross-over experimental design, to receive 16 days of supplementation with 300 mL.day(-1) of a watermelon juice concentrate, which provided ~3.4 g l-citrulline.day(-1) and an apple juice concentrate as a placebo. Participants reported to the laboratory on days 14 and 16 of supplementation to assess the effects of the interventions on blood pressure, plasma [l-citrulline], plasma [l-arginine], plasma [nitrite], muscle oxygenation and time-to-exhaustion during severe-intensity exercise. Compared to control and placebo, plasma [l-citrulline] (29 +/- 4, 22 +/- 6 and 101 +/- 23 MUM), [l-arginine] (74 +/- 9, 67 +/- 13 and 116 +/- 9 MUM) and [nitrite] (102 +/- 29, 106 +/- 21 and 201 +/- 106 nM) were higher after watermelon juice supplementation (P < 0.01). However, systolic blood pressure was higher in the watermelon juice (130 +/- 11) and placebo (131 +/- 9) conditions compared to the control condition (124 +/- 8 mmHg; P < 0.05). The skeletal muscle oxygenation index during moderate-intensity exercise was greater in the watermelon juice condition than the placebo and control conditions (P < 0.05), but time-to exhaustion during the severe-intensity exercise test (control: 478 +/- 80, placebo: 539 +/- 108, watermelon juice: 550 +/- 143 s) was not significantly different between conditions (P < 0.05). In conclusion, while watermelon juice supplementation increased baseline plasma [nitrite] and improved muscle oxygenation during moderate-intensity exercise, it increased resting blood pressure and did not improve time-to-exhaustion during severe-intensity exercise. These findings do not support the use of watermelon juice supplementation as a nutritional intervention to lower blood pressure or improve endurance exercise performance in healthy adults. PMID- 27378313 TI - Renin-Angiotensin System Inhibitors vs Other Antihypertensives in Hypertensive Blacks: A Meta-Analysis. AB - The purpose of this study was to assess the effects of renin-angiotensin system (RAS) inhibitors vs other antihypertensive agents on cardiovascular outcomes in hypertensive black patients. The authors performed a systematic review and meta analysis of studies that compared the effects of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) with calcium channel blockers (CCBs), diuretics, and beta-blockers in hypertensive black patients on cardiovascular outcomes. A total of 38,983 patients with a mean age of 60 years and mean follow-up of 4 years were included in our meta-analysis. No significant differences were found in all-cause mortality, myocardial infarction, heart failure, and cardiovascular mortality rates among patients treated with RAS inhibitors compared with CCBs, diuretics, and beta-blockers. The incidence of stroke was significantly increased in patients treated with RAS inhibitors compared with CCBs (odds ratio, 1.56; 95% confidence interval, 1.31-1.87 [P<.00001]; I2 =0%) and diuretics (odds ratio, 1.59; 95% confidence interval, 1.16-2.17 [P=.004]; I2 =56%) but not beta-blockers. PMID- 27378314 TI - First-in-human study assessing safety, tolerability and pharmacokinetics of BI 409306, a selective phosphodiesterase 9A inhibitor, in healthy males. AB - AIMS: The aim of the present study was to investigate the safety, tolerability, dose proportionality and relative bioavailability of tablet and oral solution formulations of BI 409306 in healthy male subjects, and to compare the safety and pharmacokinetics in subjects who were extensive metabolizers (EMs) or poor metabolizers (PMs) of cytochrome P450 (CYP)-2C19. METHODS: The present randomized, double-blind, placebo-controlled, single-centre study evaluated single rising doses of BI 409306 (0.5-500 mg) administered as a tablet or oral solution to EMs or PMs. RESULTS: Of 80 enrolled subjects (mean age 36.7 years), 79 (CYP2C19 EMs, 71; CYP2C19 PMs, eight) received treatment and completed the study. Adverse events (AEs) were mild to moderate in intensity. Overall, 17/71 (23.9%) EMs and 6/8 (75.0%) PMs experienced 28 and eight AEs, respectively, of which, 25 and seven AEs, respectively, were considered to be drug related. The most frequently reported AEs were nervous system and eye disorders; all occurred shortly (20-30 min) after administration and mostly resolved within 1-2 h. No serious AEs occurred. BI 409306 systemic absorption and elimination were rapid; peak plasma concentration (Cmax ) was reached <1 h after drug administration, and the half-life ranged from 0.99 h to 2.71 h. Both the tablet and oral solution resulted in similar exposures. In PMs, at dose levels of 10 mg and 100 mg, Cmax was 2.2-2.3-fold higher, and the area under the plasma concentration-time curve over the time interval 0 extrapolated to infinity was 4.1-5.0-fold higher compared with EMs. CONCLUSIONS: In healthy male subjects, BI 409306 was generally safe and well tolerated, with rapid absorption and elimination. Systemic exposure was higher in CYP2C19 PMs than EMs at the same dose level. PMID- 27378316 TI - Multidisciplinary Team Service Redesign: a Step to Improved Quality of Care for Lung Cancer Patients. PMID- 27378315 TI - Analysis of anthocyanin biosynthesis genes expression profiles in contrasting cultivars of Japanese plum (Prunus salicina L.) during fruit development. AB - Flavonoids are responsible of different fruit sensorial properties. In Japanese plum (Prunus salicina L.) these compounds are variable in both type and quantity during the different stages of fruit growth and maturation. Here we present the first study which determines the expression profile of structural genes of the flavonoid pathway and accumulation profiles of total phenols, proanthocyanidins and anthocyanins during fruit development stages in contrasting cultivars in Japanese plum. The biosynthesis of these compounds is differentially regulated in different tissues and cultivars. Our result showed that all pigmented tissues increased the expression of the leucoanthocyanidin dioxygenase (LDOX) gene, while all tissues without anthocyanin accumulation presented a minimal expression of LDOX. In addition, the regulation of putative transcription factors PsMYB10 and PsMYB1 were correlated positively and negatively with the pigmented tissues respectively, suggesting a critical and coordinated mechanism involved in the change of the fruit color. PMID- 27378318 TI - Clinical Problem Solving Series. PMID- 27378317 TI - The DSM-5 Dimensional Anxiety Scales in a Dutch non-clinical sample: psychometric properties including the adult separation anxiety disorder scale. AB - With DSM-5, the American Psychiatric Association encourages complementing categorical diagnoses with dimensional severity ratings. We therefore examined the psychometric properties of the DSM-5 Dimensional Anxiety Scales, a set of brief dimensional scales that are consistent in content and structure and assess DSM-5-based core features of anxiety disorders. Participants (285 males, 255 females) completed the DSM-5 Dimensional Anxiety Scales for social anxiety disorder, generalized anxiety disorder, specific phobia, agoraphobia, and panic disorder that were included in previous studies on the scales, and also for separation anxiety disorder, which is included in the DSM-5 chapter on anxiety disorders. Moreover, they completed the Screen for Child Anxiety Related Emotional Disorders Adult version (SCARED-A). The DSM-5 Dimensional Anxiety Scales demonstrated high internal consistency, and the scales correlated significantly and substantially with corresponding SCARED-A subscales, supporting convergent validity. Separation anxiety appeared present among adults, supporting the DSM-5 recognition of separation anxiety as an anxiety disorder across the life span. To conclude, the DSM-5 Dimensional Anxiety Scales are a valuable tool to screen for specific adult anxiety disorders, including separation anxiety. Research in more diverse and clinical samples with anxiety disorders is needed. (c) 2016 The Authors International Journal of Methods in Psychiatric Research Published by John Wiley & Sons Ltd. PMID- 27378320 TI - The Clinical Practice of Nephrology. PMID- 27378319 TI - An Autopsy of the Clinical Reasoning Process. PMID- 27378321 TI - Synthesis of Hierarchical Sb2MoO6 Architectures and Their Electrochemical Behaviors as Anode Materials for Li-Ion Batteries. AB - We report a facile microwave-hydrothermal synthesis of hierarchical Sb2MoO6 architectures assembled from single-crystalline nanobelts, which are first demonstrated as anode materials for lithium-ion batteries (LIBs) with superior electrochemical properties. Sb2MoO6 delivers a high initial reversible capacity of ~1140 mA h/g at 200 mA/g with large initial Coulombic efficiency of ~89%, and a reversible capacity of ~878 mA h/g after 100 cycles at 200 mA/g. As a new anode, the electrochemical behaviors are investigated through ex situ TEM and XPS measurements, revealing that the superior electrochemical performance is attributed to the novel hierarchical structures and the synergistic interaction between both the active Sb- and Mo-species, in which the in situ generated Li2O MoOx serves as matrix and efficiently buffers the volume changes of the Li-Sb alloying-dealloying upon cycling. PMID- 27378322 TI - Enhancement in the Neuroprotective Power of Riluzole Against Cerebral Ischemia Using a Brain Targeted Drug Delivery Vehicle. AB - Riluzole is the only available drug for motor neuron diseases quite well-known for its neuroprotective activity. But its poor aqueous solubility, short half life with some side-effects at higher concentration poses a limitation to its use as a therapeutic agent. The present study was performed to investigate the therapeutic potential of nanoriluzole (NR), i.e., riluzole encapsulated in nanoparticles against cerebral ischemia (stroke) at three different concentrations [10 (NRL), 20 (NRM), and 40 (NRH) MUg/kg body weight intraperitoneally (i.p.)]. Chitosan conjugated NIPAAM (N-isopropylacrylamide) nanoparticles coated with tween80 were synthesized through free radical polymerization. The particles were characterized with Transmission Electron Microscopy, Dynamic Light Scattering, and Fourier Transform Infrared spectroscopy and were found to have size of ~50 nm. Cerebral ischemia was induced by Middle Cerebral Artery Occlusion (MCAO) model for 1 h and NR was given intraperitoneally after 1 h of MCAO. Animals were dissected after a reperfusion period of 24 h for evaluation of various parameters. Triphenyl tetrazolium chloride staining shows substantial reduction in infarct size in all three treated groups. It was also supported by histopathological results, biochemical parameters, and behavioral studies. Immunological parameters like NOS-2, NF-kB, and COX-2 also show profound reduction in expression in NR treated groups. Thus, the present work clearly demonstrated that the nanoparticle was good enough to carry large amount of drug across the Blood Brain Barrier which results in significant neuroprotection even at a very low concentration. It also substantially lowered the required concentration by overcoming the poor aqueous solubility; hence hardly leaving any scope for side-effects. PMID- 27378323 TI - Urban case studies: general discussion. PMID- 27378324 TI - Self-monitoring and self-management of oral anticoagulation. AB - BACKGROUND: The introduction of point-of-care devices for the management of patients on oral anticoagulation allows self-testing by the patient at home. Patients who self-test can either adjust their medication according to a pre determined dose-INR (international normalized ratio) schedule (self-management), or they can call a clinic to be told the appropriate dose adjustment (self monitoring). Increasing evidence suggests self-testing of oral anticoagulant therapy is equal to or better than standard monitoring. This is an updated version of the original review published in 2010. OBJECTIVES: To evaluate the effects on thrombotic events, major haemorrhages, and all-cause mortality of self monitoring or self-management of oral anticoagulant therapy compared to standard monitoring. SEARCH METHODS: For this review update, we re-ran the searches of the Cochrane Central Register of Controlled Trials (CENTRAL), 2015, Issue 6, the Cochrane Library, MEDLINE (Ovid, 1946 to June week 4 2015), Embase (Ovid, 1980 to 2015 week 27) on 1 July 2015. We checked bibliographies and contacted manufacturers and authors of relevant studies. We did not apply any language restrictions . SELECTION CRITERIA: Outcomes analysed were thromboembolic events, mortality, major haemorrhage, minor haemorrhage, tests in therapeutic range, frequency of testing, and feasibility of self-monitoring and self-management. DATA COLLECTION AND ANALYSIS: Review authors independently extracted data and we used a fixed-effect model with the Mantzel-Haenzel method to calculate the pooled risk ratio (RR) and Peto's method to verify the results for uncommon outcomes. We examined heterogeneity amongst studies with the Chi(2) and I(2) statistics and used GRADE methodology to assess the quality of evidence. MAIN RESULTS: We identified 28 randomised trials including 8950 participants (newly incorporated in this update: 10 trials including 4227 participants). The overall quality of the evidence was generally low to moderate. Pooled estimates showed a reduction in thromboembolic events (RR 0.58, 95% CI 0.45 to 0.75; participants = 7594; studies = 18; moderate quality of evidence). Both, trials of self-management or self-monitoring showed reductions in thromboembolic events (RR 0.47, 95% CI 0.31 to 0.70; participants = 3497; studies = 11) and (RR 0.69, 95% CI 0.49 to 0.97; participants = 4097; studies = 7), respectively; the quality of evidence for both interventions was moderate. No reduction in all-cause mortality was found (RR 0.85, 95% CI 0.71 to 1.01; participants = 6358; studies = 11; moderate quality of evidence). While self-management caused a reduction in all-cause mortality (RR 0.55, 95% CI 0.36 to 0.84; participants = 3058; studies = 8); self-monitoring did not (RR 0.94, 95% CI 0.78 to 1.15; participants = 3300; studies = 3); the quality of evidence for both interventions was moderate. In 20 trials (8018 participants) self-monitoring or self-management did not reduce major haemorrhage (RR 0.95, 95% CI, 0.80 to 1.12; moderate quality of evidence). There was no significant difference found for minor haemorrhage (RR 0.97, 95% CI 0.67 to 1.41; participants = 5365; studies = 13). The quality of evidence was graded as low because of serious risk of bias and substantial heterogeneity (I(2) = 82%). AUTHORS' CONCLUSIONS: Participants who self-monitor or self-manage can improve the quality of their oral anticoagulation therapy. Thromboembolic events were reduced, for both those self-monitoring or self-managing oral anticoagulation therapy. A reduction in all-cause mortality was observed in trials of self management but not in self-monitoring, with no effects on major haemorrhage. PMID- 27378325 TI - Commentary: Interpersonal style should be included in taxonomies of behavior change techniques. PMID- 27378327 TI - Hydrocortisone Counteracts Adverse Stress Effects on Dual-Task Performance by Improving Visual Sensory Processes. AB - The impact of acute stress on executive processes is commonly attributed to glucocorticoid-induced disruptions of the pFC. However, the occipital cortex seems to express a higher density of glucocorticoid receptors. Consequently, acute stress effects on executive processes could as well be mediated by glucocorticoid (e.g., cortisol)-induced alterations of visual sensory processes. To investigate this alternative route of stress action by demarcating the effects of acute stress and cortisol on executive from those on visual sensory processes, 40 healthy young men completed a standardized stress induction (i.e., the Trier Social Stress Test) and control protocol in two consecutive sessions. In addition, they received either a placebo or hydrocortisone (0.12-mg/kg bodyweight) pill and processed a dual and a partial report task to assess their executive and visual sensory processing abilities, respectively. Hydrocortisone administration improved both partial report and dual-task performance as indicated by increased response accuracies and/or decreased RTs. Intriguingly, the hydrocortisone-induced increase in dual-task performance was completely mediated by its impact on partial report performance (i.e., visual sensory processes). Moreover, RT measures in both tasks shared approximately 26% of variance, which was only in part attributable to hydrocortisone administration (DeltaR2 = 8%). By contrast, acute stress selectively impaired dual-task performance (i.e., executive processes), presumably through an alternative route of action. In summary, the present results suggest that cortisol secretion (as mimicked by hydrocortisone administration) may counteract adverse residual stress effects on executive processes by improving visual sensory processes (e.g., the maintenance and amplification of task-relevant sensory information). PMID- 27378328 TI - An Anatomical Interface between Memory and Oculomotor Systems. AB - Visual behavior is guided by memories from prior experience and knowledge of the visual scene. The hippocampal system (HC), in particular, has been implicated in the guidance of saccades: Amnesic patients, following damage to the HC, exhibit selective deficits in their gaze patterns. However, the neural circuitry by which mnemonic representations influence the oculomotor system remains unknown. We used a data-driven, network-based approach on directed anatomical connectivity from the macaque brain to reveal an extensive set of polysnaptic pathways spanning the extrastriate, posterior parietal and prefrontal cortices that potentially mediate the exchange of information between the memory and visuo-oculomotor systems. We additionally show how the potential for directed information flow from the hippocampus to oculomotor control areas is exceptionally high. In particular, the dorsolateral pFC and FEF-regions known to be responsible for the cognitive control of saccades-are topologically well positioned to receive information from the hippocampus. Together with neuropsychological evidence of altered gaze patterns following damage to the hippocampus, our findings suggest that a reconsideration of hippocampal involvement in oculomotor guidance is needed. PMID- 27378326 TI - Altruism, personal benefit, and anxieties: a phenomenological study of healthy volunteers' experiences in a placebo-controlled trial of duloxetine. AB - OBJECTIVE: The objective of this study was to develop an in-depth understanding of healthy volunteers' experiences of mental health trials. METHODS: A qualitative study was nested within a healthy volunteer placebo-controlled trial of duloxetine, a psychotropic drug used for treating patients with major depression and generalized anxiety disorder. Eight participants were interviewed, and data were analyzed using interpretative phenomenological analysis. RESULTS: Interviewees described volunteering for the trial because they were interested in research, wanted the monetary incentive, wanted to help researchers, and wanted to be part of something. On entering the trial, participants considered the possible risks and described feeling anxious, excited, and determined; they had some clear expectations and some loosely held hopes about what would happen. During the trial, participants were curious about whether they were taking duloxetine or placebo, self-monitored their bodies' reactions, and guessed which treatment they received. On being un-blinded to treatment allocation after completing the trial, some participants' guesses were confirmed, but others were surprised, and a few were disappointed. CONCLUSIONS: Small changes to advertising/consent materials to reflect volunteers' motivations could improve recruitment rates to similar trials; "active" placebos might be particularly useful for maintaining blinding in healthy volunteer trials; and sensitive procedures are needed for un-blinding participants to treatment allocation. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27378329 TI - Visual Category Learning Results in Rapid Changes in Brain Activation Reflecting Sensitivity to the Category Relation between Perceived Objects and to Decision Correctness. AB - Little is known about the time scales in which sensitivity to novel category identity may become evident in visual and executive cortices in visual category learning (VCL) tasks and the nature of such changes in brain activation. We used fMRI to investigate the processing of category information and trial-by-trial feedback information. In each VCL task, stimuli differed in three feature dimensions. In each trial, either two same-category stimuli or two different categories stimuli were presented. The participant had to learn which feature dimension was relevant for categorization based on the feedback that followed each categorization decision. We contrasted between same-category stimuli trials and different-category trials and between correct and incorrect categorization decision trials. In each trial, brain activation in the visual stimuli processing phase was modeled separately from activation during the later feedback processing phase. We found activation in the lateral occipital complex, indicating sensitivity to the category relation between stimuli, to be evident in VCL within only few learning trials. Specifically, greater lateral occipital complex activation was evident when same-category stimuli were presented than when different-category stimuli were presented. In the feedback processing phase, greater activation in both executive and visual cortices was evident primarily after "misdetections" of same-category stimuli. Implications regarding the contribution of different learning trials to VCL, and the respective role of key brain regions, at the onset of VCL, are discussed. PMID- 27378331 TI - Empathy or Ownership? Evidence from Corticospinal Excitability Modulation during Pain Observation. AB - Recent studies show that motor responses similar to those present in one's own pain (freezing effect) occur as a result of observation of pain in others. This finding has been interpreted as the physiological basis of empathy. Alternatively, it can represent the physiological counterpart of an embodiment phenomenon related to the sense of body ownership. We compared the empathy and the ownership hypotheses by manipulating the perspective of the observed hand model receiving pain so that it could be a first-person perspective, the one in which embodiment occurs, or a third-person perspective, the one in which we usually perceive the others. Motor-evoked potentials (MEPs) by TMS over M1 were recorded from first dorsal interosseous muscle, whereas participants observed video clips showing (a) a needle penetrating or (b) a Q-tip touching a hand model, presented either in first-person or in third-person perspective. We found that a pain-specific inhibition of MEP amplitude (a significantly greater MEP reduction in the "pain" compared with the "touch" conditions) only pertains to the first-person perspective, and it is related to the strength of the self reported embodiment. We interpreted this corticospinal modulation according to an "affective" conception of body ownership, suggesting that the body I feel as my own is the body I care more about. PMID- 27378332 TI - Reaching-related Neurons in Superior Parietal Area 5: Influence of the Target Visibility. AB - Reaching movements require the integration of both somatic and visual information. These signals can have different relevance, depending on whether reaches are performed toward visual or memorized targets. We tested the hypothesis that under such conditions, therefore depending on target visibility, posterior parietal neurons integrate differently somatic and visual signals. Monkeys were trained to execute both types of reaches from different hand resting positions and in total darkness. Neural activity was recorded in Area 5 (PE) and analyzed by focusing on the preparatory epoch, that is, before movement initiation. Many neurons were influenced by the initial hand position, and most of them were further modulated by the target visibility. For the same starting position, we found a prevalence of neurons with activity that differed depending on whether hand movement was performed toward memorized or visual targets. This result suggests that posterior parietal cortex integrates available signals in a flexible way based on contextual demands. PMID- 27378330 TI - Temporal Tuning of Word- and Face-selective Cortex. AB - Sensitivity to temporal change places fundamental limits on object processing in the visual system. An emerging consensus from the behavioral and neuroimaging literature suggests that temporal resolution differs substantially for stimuli of different complexity and for brain areas at different levels of the cortical hierarchy. Here, we used steady-state visually evoked potentials to directly measure three fundamental parameters that characterize the underlying neural response to text and face images: temporal resolution, peak temporal frequency, and response latency. We presented full-screen images of text or a human face, alternated with a scrambled image, at temporal frequencies between 1 and 12 Hz. These images elicited a robust response at the first harmonic that showed differential tuning, scalp topography, and delay for the text and face images. Face-selective responses were maximal at 4 Hz, but text-selective responses, by contrast, were maximal at 1 Hz. The topography of the text image response was strongly left-lateralized at higher stimulation rates, whereas the response to the face image was slightly right-lateralized but nearly bilateral at all frequencies. Both text and face images elicited steady-state activity at more than one apparent latency; we observed early (141-160 msec) and late (>250 msec) text- and face-selective responses. These differences in temporal tuning profiles are likely to reflect differences in the nature of the computations performed by word- and face-selective cortex. Despite the close proximity of word- and face selective regions on the cortical surface, our measurements demonstrate substantial differences in the temporal dynamics of word- versus face-selective responses. PMID- 27378333 TI - Prefrontal Cortex Activation Reflects Efficient Exploitation of Higher-order Statistical Structure. AB - Because everyday actions are statistically structured, knowing which action a person has just completed allows predicting the most likely next action step. Taking even more than the preceding action into account improves this predictability but also causes higher processing costs. Using fMRI, we investigated whether observers exploit second-order statistical regularities preferentially if information on possible upcoming actions provided by first order regularities is insufficient. We hypothesized that anterior pFC balances whether or not second-order information should be exploited. Participants watched videos of actions that were structured by first- and second-order conditional probabilities. Information provided by the first and by the second order was manipulated independently. BOLD activity in the action observation network was more attenuated the more information on upcoming actions was provided by first order structure, reflecting expectation suppression for more predictable actions. Activation in posterior parietal sites decreased further with second-order information but increased in temporal areas. As expected, second-order information was integrated more when less first-order information was provided, and this interaction was mediated by anterior pFC (BA 10). Observers spontaneously used both the present and the preceding action to predict the upcoming action, and integration of the preceding action was enhanced when the present action was uninformative. PMID- 27378334 TI - Impairment of contextual fear extinction by chronic nicotine and withdrawal from chronic nicotine is associated with hippocampal nAChR upregulation. AB - Chronic nicotine and withdrawal from chronic nicotine have been shown to be major modulators of fear learning behavior. Moreover, recent studies from our laboratory have shown that acute nicotine impaired fear extinction and safety learning in mice. However, the effects of chronic nicotine and withdrawal on fear extinction are unknown. Therefore, the current experiments were conducted to investigate the effects of chronic nicotine as well as withdrawal from chronic nicotine on contextual fear extinction in mice. C57BL6/J mice were given contextual fear conditioning training and retention testing during chronic nicotine administration. Mice then received contextual fear extinction either during chronic nicotine or during withdrawal from chronic nicotine. Our results showed that contextual fear extinction was impaired both during chronic nicotine administration and subsequent withdrawal. However, it was also observed that the effects of prior chronic nicotine disappeared after 72 h in withdrawal, a timeline that closely matches with the timing of the chronic nicotine-induced upregulation of hippocampal nicotinic acetylcholine receptor (nAChR) density. Additional experiments found that 4 days, but not 1 day, of continuous nicotine administration upregulated hippocampal nAChRs and impaired contextual fear extinction. These effects disappeared following 72 h withdrawal. Overall, these experiments provide a potential link between nicotine-induced upregulation of hippocampal nAChRs and fear extinction deficits observed in patients with anxiety disorders, which may lead to advancements in the pharmacological treatment methods for this disorder. PMID- 27378335 TI - Stress-induced resistance to the fear memory labilization/reconsolidation process. Involvement of the basolateral amygdala complex. AB - Consolidated memories can enter into a labile state after reactivation followed by a restabilization process defined as reconsolidation. This process can be interfered with Midazolam (MDZ), a positive allosteric modulator of the GABA-A receptor. The present study has evaluated the influence of prior stress on MDZ's interfering effect. We also assessed the influence of both systemic and intra basolateral amygdala (BLA) infusion of d-cycloserine (DCS), a partial agonist of the NMDA receptors, on the MDZ effect in previously stressed rats. Furthermore, we analyzed the effect of stress on the expression of Zif-268 and the GluN2B sites, two molecular markers of the labilization/reconsolidation process, following reactivation. The results revealed that prior stress resulted into a memory trace that was insensitive to the MDZ impairing effect. Both systemic and intra-BLA DCS administration previous to reactivation restored MDZ's disruptive effect on memory reconsolidation in stressed animals. Further, reactivation enhanced Zif-268 expression in the BLA in control unstressed rats, whereas no elevation was observed in stressed animals. In agreement with the behavioral findings, DCS restored the increased level of Zif-268 expression in the BLA in stressed animals. Moreover, memory reactivation in unstressed animals elevated GluN2B expression in the BLA, thus suggesting that this effect is involved in memory destabilization, whereas stressed animals did not reveal any changes. These findings are consistent with resistance to the MDZ effect in these rats, indicating that stress exposure prevents the onset of destabilization following reactivation. In summary, prior stress limited both the occurrence of the reactivation-induced destabilization and restabilization. PMID- 27378336 TI - The BDNF Val66Met polymorphism enhances glutamatergic transmission but diminishes activity-dependent synaptic plasticity in the dorsolateral striatum. AB - The Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene disrupts the activity-dependent release of BDNF, which might underlie its involvement in several neuropsychiatric disorders. Consistent with the potential role of regulated release of BDNF in synaptic functions, earlier studies have demonstrated that the BDNF Val66Met polymorphism impairs NMDA receptor-mediated synaptic transmission and plasticity in the hippocampus, the medial prefrontal cortex and the central amygdala. However, it is unknown whether the BDNF Val66Met polymorphism affects synapses in the dorsal striatum, which depends on cortical afferents for BDNF. Electrophysiological experiments revealed an enhanced glutamatergic transmission in the dorsolateral striatum (DLS) of knock-in mice containing the variant polymorphism (BDNFMet/Met) compared to the wild-type (BDNFVal/Val) mice. This increase in glutamatergic transmission is mediated by a potentiation in glutamate release and NMDA receptor transmission in the medium spiny neurons without any alterations in non-NMDA receptor-mediated transmission. We also observed an impairment of synaptic plasticity, both long-term potentiation and depression in the DLS neurons, in BDNFMet/Met mice. Thus, the BDNF Val66Met polymorphism exerts an increase in glutamatergic transmission but impairs synaptic plasticity in the dorsal striatum, which might play a role in its effect on neuropsychiatric symptoms. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'. PMID- 27378337 TI - Involvement of ventral tegmental area ionotropic glutamate receptors in the expression of ethanol-induced conditioned place preference. AB - The ventral tegmental area (VTA) is a well-established neural substrate of reward related processes. Activity within this structure is increased by the primary and conditioned rewarding effects of abused drugs and its engagement is heavily reliant on excitatory input from structures upstream. In the case of drug seeking, it is thought that exposure to drug-associated cues engages glutamatergic VTA afferents that signal directly to dopamine cells, thereby triggering this behavior. It is unclear, however, whether glutamate input to VTA is directly involved in ethanol-associated cue seeking. Here, the role of intra VTA ionotropic glutamate receptor (iGluR) signaling in ethanol-cue seeking was evaluated in DBA/2J mice using an ethanol conditioned place preference (CPP) procedure. Intra-VTA iGluRs alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPAR)/kainate and N-methyl-d-aspartate (NMDAR) were blocked during ethanol CPP expression by co-infusion of antagonist drugs 6,7-dinitroquinoxaline-2,3 dione (DNQX; AMPA/kainate) and d-(-)-2-Amino-5-phosphonopentanoic acid (AP5; NMDA). Compared to aCSF, bilateral infusion of low (1 DNQX+100 AP5ng/side) and high (5 DNQX+500 AP5ng/side) doses of the AMPAR and NMDAR antagonist cocktail into VTA blocked ethanol CPP expression. This effect was site specific, as DNQX/AP5 infusion proximal to VTA did not significantly impact CPP expression. An increase in activity was found at the high but not low dose of DNQX/AP5. These findings demonstrate that activation of iGluRs within the VTA is necessary for ethanol-associated cue seeking, as measured by CPP. PMID- 27378338 TI - M100907 attenuates elevated grooming behavior in the BTBR mouse. AB - Individuals with autism spectrum disorder (ASD) exhibit social-communication deficits along with restricted interests and repetitive behaviors (RRBs). To date, there is a lack of effective treatments to alleviate RRBs. A recent study found that treatment with the 5HT2A receptor antagonist M100907 attenuates a reversal learning deficit in the BTBR mouse model of autism. The BTBR mouse also exhibits elevated grooming behavior which may model stereotyped motor behaviors also observed in ASD. The present study examined whether 5HT2A receptor blockade with M100907 at either 0.01 or 0.1mg/kg can reduce repetitive grooming in BTBR mice compared to that of vehicle-treated BTBR and C57BL6/J (B6) mice. M100907 at 0.1mg/kg, but not 0.01mg/kg, significantly attenuated repetitive grooming in BTBR mice compared to that of vehicle-treated BTBR mice. M100907 at either dose did not affect grooming behavior in B6 mice. To determine whether 0.1mg/kg M100907 had a more general effect on activity in BTBR mice, a second experiment determined whether M100907 at 0.1mg/kg affected locomotor activity in BTBR mice. M100907 treatment in BTBR and B6 mice did not alter locomotor activity compared to that of vehicle-treated BTBR and B6 mice. The present findings taken together with past results suggest that treatment with a 5HT2A receptor antagonist may be effective in ameliorating RRBs in ASD. PMID- 27378339 TI - Significant variations in alternative splicing patterns and expression profiles between human-mouse orthologs in early embryos. AB - Human and mouse orthologs are expected to have similar biological functions; however, many discrepancies have also been reported. We systematically compared human and mouse orthologs in terms of alternative splicing patterns and expression profiles. Human-mouse orthologs are divergent in alternative splicing, as human orthologs could generally encode more isoforms than their mouse orthologs. In early embryos, exon skipping is far more common with human orthologs, whereas constitutive exons are more prevalent with mouse orthologs. This may correlate with divergence in expression of splicing regulators. Orthologous expression similarities are different in distinct embryonic stages, with the highest in morula. Expression differences for orthologous transcription factor genes could play an important role in orthologous expression discordance. We further detected largely orthologous divergence in differential expression between distinct embryonic stages. Collectively, our study uncovers significant orthologous divergence from multiple aspects, which may result in functional differences and dynamics between human-mouse orthologs during embryonic development. PMID- 27378340 TI - WNK3 interacts with NCC. PMID- 27378341 TI - Expanding the antigenic repertoire of CAR-T cells with "TCR-like" antibody specificity. PMID- 27378342 TI - Therapeutic efficacy of bone marrow derived mesenchymal stromal cells versus losartan on adriamycin-induced renal cortical injury in adult albino rats. AB - BACKGROUND: Renal disease is a major health problem. Recent studies have reported the efficacy of stem cell therapy in nephropathy animal models. AIM OF THE WORK: This study was designed to investigate the therapeutic effectiveness of bone marrow-derived mesenchymal stromal cells (MSCs) versus losartan in the treatment of renal alterations induced by adriamycin (ADR). MATERIALS AND METHODS: Thirty five adult male albino rats were divided into four groups. Group I was the control group. Group II (adriamycin-treated group),which included ten rats that were injected with a single dose of adriamycin (15 mg/kg) intraperitoneally, was subdivided into subgroup IIa and IIb and they were sacrificed 1 week and 5 weeks after adriamycin injection, respectively. Group III was the adriamycin + losartan treated group and 1 week after adriamycin injection five rats received 10 mg/kg of losartan orally and daily for 4 weeks. Group IV was the adriamycin + MSC treated group); five rats were injected with adriamycin as group II then supplied with MSCs at a dose of 1 * 10(6) cells suspended in 0.5 mL of phosphate-buffered saline (PBS) per rat in the tail vein 1 week after adriamycin injection. Rats of this group were sacrificed 4 weeks after the stem cell injection. Blood urea nitrogen and serum creatinine were measured. Samples from renal cortex were processed for light and electron microscope examination. As regards light microscope, sections were stained with hematoxylin and eosin (H-E), periodic acid Schiff (PAS), masson trichrome, proliferating cell nuclear antigen (PCNA) and Caspase-3 immunohistochemical stains. Morphometrical and statistical analyses were also conducted. RESULTS: Examination of adriamycin-treated group revealed deterioration of renal functions and various degrees of renal structural alterations as vacuolated cytoplasm, dark nuclei and detached epithelial lining. Administration of losartan partially improved ADR-induced kidney dysfunction, whereas MSCs denoted a more ameliorative role evidenced by structural and functional recovery. CONCLUSION: MSCs have a relevant therapeutic potential against ADR-induced renal damage. MSCs may accomplish this role by decreasing caspase-3 expression and increasing proliferating cell nuclear antigen staining which influence the regeneration of the kidney. PMID- 27378343 TI - PR1-specific cytotoxic T lymphocytes are relatively frequent in umbilical cord blood and can be effectively expanded to target myeloid leukemia. AB - BACKGROUND AIMS: PR1 is an HLA-A2 restricted leukemia-associated antigen derived from neutrophil elastase and proteinase 3, both of which are normally stored in the azurophil granules of myeloid cells but overexpressed in myeloid leukemic cells. PR1-specific cytotoxic lymphocytes (PR1-CTLs) have activity against primary myeloid leukemia in vitro and in vivo and thus could have great potential in the setting of adoptive cellular therapy (ACT). Adult peripheral blood-derived PR1-CTLs are infrequent but preferentially lyse myeloid leukemia cells. We sought to examine PR1-CTLs in umbilical cord blood (UCB) because UCB units provide a rapidly available cell source and a lower risk of graft-versus-host disease, even in the setting of mismatched human leukocyte antigen (HLA) loci. METHODS: We first determined the frequency of PR1-CTLs in HLA-A2(+) UCB units and then successfully expanded them ex vivo using repeated stimulation with PR1 peptide pulsed antigen-presenting cells (APCs). After expansion, we assessed the PR1-CTL phenotype (naive, effector, memory) and function against PR1-expressing target cells. RESULTS: PR1-CTLs are detected at an average frequency of 0.14% within the CD8(+) population of fresh UCB units, which is 45 times higher than in healthy adult peripheral blood. UCB PR1-CTLs are phenotypically naive, consistent with the UCB CD8(+) population as a whole. In addition, the cells can be expanded by stimulation with PR1 peptide-pulsed APCs. Expansion results in an increased frequency of PR1-CTLs, up to 4.56%, with an average 20-fold increase in total number. After expansion, UCB PR1-CTLs express markers consistent with effector memory T cells. Expanded UCB PR1-CTLs are functional in vitro as they are able to produce cytokines and lyse PR1-expressing leukemia cell lines. CONCLUSIONS: This study is the first report to show that T cells specific for a leukemia-associated antigen are found at a significantly higher frequency in UCB than adult blood. Our results also demonstrate specific cytotoxicity of expanded UCB-derived PR1 CTLs against PR1-expressing targets. Together, our data suggest that UCB PR1-CTLs could be useful to prevent or treat leukemia relapse in myeloid leukemia patients. PMID- 27378344 TI - Automated manufacturing of chimeric antigen receptor T cells for adoptive immunotherapy using CliniMACS prodigy. AB - Novel cell therapies derived from human T lymphocytes are exhibiting enormous potential in early-phase clinical trials in patients with hematologic malignancies. Ex vivo modification of T cells is currently limited to a small number of centers with the required infrastructure and expertise. The process requires isolation, activation, transduction, expansion and cryopreservation steps. To simplify procedures and widen applicability for clinical therapies, automation of these procedures is being developed. The CliniMACS Prodigy (Miltenyi Biotec) has recently been adapted for lentiviral transduction of T cells and here we analyse the feasibility of a clinically compliant T-cell engineering process for the manufacture of T cells encoding chimeric antigen receptors (CAR) for CD19 (CAR19), a widely targeted antigen in B-cell malignancies. Using a closed, single-use tubing set we processed mononuclear cells from fresh or frozen leukapheresis harvests collected from healthy volunteer donors. Cells were phenotyped and subjected to automated processing and activation using TransAct, a polymeric nanomatrix activation reagent incorporating CD3/CD28-specific antibodies. Cells were then transduced and expanded in the CentriCult-Unit of the tubing set, under stabilized culture conditions with automated feeding and media exchange. The process was continuously monitored to determine kinetics of expansion, transduction efficiency and phenotype of the engineered cells in comparison with small-scale transductions run in parallel. We found that transduction efficiencies, phenotype and function of CAR19 T cells were comparable with existing procedures and overall T-cell yields sufficient for anticipated therapeutic dosing. The automation of closed-system T-cell engineering should improve dissemination of emerging immunotherapies and greatly widen applicability. PMID- 27378345 TI - Safety, immune and clinical responses in metastatic melanoma patients vaccinated with a long peptide derived from indoleamine 2,3-dioxygenase in combination with ipilimumab. AB - BACKGROUND AIM: Indoleamine 2,3-dioxygenase (IDO) is an emerging new target in cancer therapy that can be targeted with active immunotherapy (e.g. through peptide vaccination). Furthermore, IDO has been identified as a key mechanism underlying resistance to treatment with the checkpoint blocking antibody ipilimumab (ipi). METHODS: Ten patients with metastatic melanoma participated in a phase I first-in-human clinical study assessing safety of combining ipi with a 21-mer synthetic peptide vaccine from IDO denoted IDOlong. Secondary and tertiary end points included vaccine and clinical response. RESULTS: Treatment was generally safe and well tolerated. Vaccine related adverse reactions included grade I and II erythema, oedema and pruritus at the vaccination site, which were manageable with mild topical corticosteroids. One patient developed presumed ipi induced colitis. It initially responded to high-dose parenteral corticosteroids but later relapsed while the patient was admitted to a local hospital, where he died after receiving suboptimal therapy. Vaccine-specific T-cell responses were detectable ex vivo in three patients. At first evaluation, five of the 10 treated patients were in stable disease, one of whom had an unconfirmed partial response. CONCLUSIONS: Treatment with IDOlong synthetic peptide vaccine in combination with ipi was generally safe and without augmented toxicity. The vaccine induced readily detectable T-cell responses in a subset of patients. Treatment showed signs of clinical activity, although not exceeding efficacy of ipi alone. Results should be confirmed in a larger study. PMID- 27378346 TI - 'Classic Papers' in this issue of Acta Radiologica. PMID- 27378347 TI - A Case of Calculous Pericarditis. PMID- 27378349 TI - Foreword. PMID- 27378348 TI - The Roentgen Diagnosis of Ulcus Duodeni with Respect to the Local Direct Roentgen Symptoms. PMID- 27378351 TI - Disclaimer. PMID- 27378353 TI - Abstracts for the British Association of Dermatologists 96th Annual Meeting, Birmingham, U.K., 5-7 July 2016. PMID- 27378354 TI - Teaching communication and supporting autonomy with a team-based operative simulator. AB - BACKGROUND: Changing residency structure emphasizes the need for formal instruction on team leadership and intraoperative teaching skills. A high fidelity, multi-learner surgical simulation may offer opportunities for senior learners (SLs) to learn these skills while teaching technical skills to junior learners (JLs). METHODS: We designed and optimized a low-cost inguinal hernia model that paired JLs and SLs as an operative team. This was tested in 3 pilot simulations. Participants' feedback was analyzed using qualitative methods. RESULTS: JL feedback to SLs included the themes "guiding and instructing" and "allowing autonomy." Senior Learner feedback to JLs focused on "mechanics," "knowledge," and "perspective/flow." Both groups focused on "communication" and "professionalism." CONCLUSIONS: A multi-learner simulation can successfully meet the technical learning needs of JLs and the teaching and communication learning needs of SLs. This model of resident-driven simulation may illustrate future opportunities for operative simulation. PMID- 27378355 TI - Mitotic genes are transcriptionally upregulated in the fibroblast irradiated with very low doses of UV-C. AB - Ultraviolet (UV) radiation induces a variety of biological effects, including DNA damage response and cell signaling pathways. We performed transcriptome analysis using microarray in human primary cultured fibroblasts irradiated with UV-C (0.5 or 5 J/m(2)) and harvested at 4 or 12 h following UV exposure. All transcript data were analyzed by comparison with the corresponding results in non-irradiated (control) cells. The number of genes with significantly altered expression (>=2 fold difference relative to the control) is higher in the sample irradiated with high dose of UV, suggesting that gene expression was UV dose-dependent. Pathway analysis on the upregulated genes at 12 h indicates that the expression of some cell cycle-related genes was predominantly induced irrespective of UV-dose. Interestingly, almost all the genes with significant altered expression were cell cycle-related genes designated as 'Mitotic Genes', which function in the spindle assembly checkpoint. Therefore, even a low dose of UV could affect the transcriptional profile. PMID- 27378356 TI - High-throughput sequencing and de novo transcriptome assembly of Swertia japonica to identify genes involved in the biosynthesis of therapeutic metabolites. AB - KEY MESSAGE: Here, we report potential transcripts involved in the biosynthesis of therapeutic metabolites in Swertia japonica , the first report of transcriptome assembly, and characterization of the medicinal plant from Swertia genus. Swertia genus, representing over 170 plant species including herbs such as S. chirata, S. hookeri, S. longifolia, S. japonica, among others, have been used as the traditional medicine in China, India, Korea, and Japan for thousands of years. Due to the lack of genomic and transcriptomic resources, little is known about the molecular basis involved in the biosynthesis of characteristic key bioactive metabolites. Here, we performed deep-transcriptome sequencing for the aerial tissues and the roots of S. japonica, generating over 2 billion raw reads with an average length of 101 bps. Using a combined approach of three popular assemblers, de novo transcriptome assembly for S. japonica was obtained, yielding 81,729 unigenes having an average length of 884 bps and N50 value of 1452 bps, of which 46,963 unigenes were annotated based on the sequence similarity against NCBI-nr protein database. Annotation of transcriptome assembly resulted in the identification of putative genes encoding all enzymes from the key therapeutic metabolite biosynthesis pathways. Transcript abundance analysis, gene ontology enrichment analysis, and KEGG pathway enrichment analysis revealed metabolic processes being up-regulated in the aerial tissues with respect to the roots of S. japonica. We also identified 37 unigenes as potential candidates involved in the glycosylation of bioactive metabolites. Being the first report of transcriptome assembly and annotation for any of the Swertia species, this study will be a valuable resource for future investigations on the biosynthetic pathways of therapeutic metabolites and their regulations. PMID- 27378357 TI - Improvement in Aqueous Solubility of Retinoic Acid Receptor (RAR) Agonists by Bending the Molecular Structure. AB - Aqueous solubility is a key requirement for many functional molecules, e. g., drug candidates. Decrease of the partition coefficient (log P) by chemical modification, i.e., introduction of hydrophilic group(s) into molecules, is a classical strategy for improving aqueous solubility. We have been investigating alternative strategies for improving the aqueous solubility of pharmaceutical compounds by disrupting intermolecular interactions. Here, we show that introducing a bend into the molecular structure of retinoic acid receptor (RAR) agonists by changing the substitution pattern from para to meta or ortho dramatically enhances aqueous solubility by up to 890-fold. We found that meta analogs exhibit similar hydrophobicity to the parent para compound, and have lower melting points, supporting the idea that the increase of aqueous solubility was due to decreased intermolecular interactions in the solid state as a result of the structural changes. PMID- 27378359 TI - Uncoupling Mitochondrial Respiration for Diabesity. AB - Until recently, the mechanism of adaptive thermogenesis was ascribed to the expression of uncoupling protein 1 (UCP1) in brown and beige adipocytes. UCP1 is known to catalyze a proton leak of the inner mitochondrial membrane, resulting in uncoupled oxidative metabolism with no production of adenosine triphosphate and increased energy expenditure. Thus increasing brown and beige adipose tissue with augmented UCP1 expression is a viable target for obesity-related disorders. Recent work demonstrates an UCP1-independent pathway to uncouple mitochondrial respiration. A secreted enzyme, PM20D1, enriched in UCP1+ adipocytes, exhibits catalytic and hydrolytic activity to reversibly form N-acyl amino acids. N-acyl amino acids act as endogenous uncouplers of mitochondrial respiration at physiological concentrations. Administration of PM20D1 or its products, N-acyl amino acids, to diet-induced obese mice improves glucose tolerance by increasing energy expenditure. In short-term studies, treated animals exhibit no toxicity while experiencing 10% weight loss primarily of adipose tissue. Further study of this metabolic pathway may identify novel therapies for diabesity, the disease state associated with diabetes and obesity. PMID- 27378358 TI - Dynamics of pyrethroid resistance in malaria vectors in southern Benin following a large scale implementation of vector control interventions. AB - BACKGROUND: Large-scale implementation of Indoor Residual Spraying and Insecticide Treated Nets has been implemented in Plateau Department, Benin between 2011 and 2014. The purpose of this study was to monitor the frequency and mechanisms of pyrethroid resistance in malaria vectors following the implementation of vector control tools for malaria prevention. METHODS: Anopheles larvae were collected in 13 villages twice a year from 2012 to 2014. WHO tube tests were used to assess the phenotypic resistance of each population to 0.05 % deltamethrin. Sibling species within Anopheles gambiae complex were identified by PCR techniques. Taqman and biochemical assays were performed to identify the presence of kdr mutations in individual mosquitoes and to detect any increase in the activity of enzymes putatively involved in insecticide metabolism (oxidases, esterase and glutathione-S-transferases). Quantitative real time PCR was used to measure the expression of three metabolic genes involved in pyrethroid resistance (CYP6P3, CYP6M2 and GSTD3). RESULTS: Anopheles populations showed < 90 % mortality to deltamethrin in all villages and at all time points. The 1014 F kdr allele frequency was close to fixation (> 0.9) over the sampling periods in both An. gambiae and An. coluzzii. Biochemical assays showed higher activities of alpha esterase and GST in field malaria vector populations compared to susceptible mosquitoes. qPCR assays showed a significant increase of CYP6P3, CYP6M2 GSTD3 expression in An. gambiae after a three-year implementation of LLINs. CONCLUSION: The study confirmed that deltamethrin resistance is widespread in malaria vectors in Southern Benin. We suspect that the increase in deltamethrin resistance between 2012 and 2014 resulted from an increased expression of metabolic detoxification genes (CYP6M2 and CYP6P3) rather than from kdr mutations. It is urgent to evaluate further the impact of metabolic resistance on the efficacy of vector control interventions using pyrethroid insecticides. PMID- 27378360 TI - An algorithm for using expanded cervical flaps to resurface facial defects based on five different methods. AB - BACKGROUND: For patients with healthy skin in the cervical region, the expanded cervical flap method is highly recommended for resurfacing facial skin defects. Many methods exist that use an expanded cervical flap. However, a gold standard for selecting the appropriate method for each patient is lacking. Here, we introduce 5 basic principles for how to use an expanded cervical flap and an algorithm for selecting the appropriate method. METHODS: The authors reviewed the medical records for all patients treated with an expanded cervical flap to restore a facial skin lesion in Shanghai's Ninth People's Hospital between 2010 and 2015. RESULTS: We summarized the 5 techniques according to different types of facial deformities: (1) an advancement of the expanded cervical flap; (2) an expanded cervical flap that is rotated toward the temporal side (the rotation pivot is located in the angle of the mandible); (3) an expanded cervical flap that is rotated toward the nasal side (the rotation pivot is located in the mentum; (4) an expanded cervical flap that is rotated cephalically along the midline toward the lower third of the face (the rotation pivot is located in the bilateral angle of the mandible); and (5) a prefabricated cervical flap that is used with superficial temporal vessels. CONCLUSION: By using this algorithm and following five basic principles, all facial defects except for those on the nose and forehead can be resurfaced using an expanded cervical skin flap. PMID- 27378361 TI - A review of negative-pressure wound therapy in the management of burn wounds. AB - OBJECTIVE: Negative pressure has been employed in various aspects of burn care and the aim of this study was to evaluate the evidence for each of those uses. METHODS: The PubMed and Cochrane CENTRAL databases were queried for articles in the following areas: negative pressure as a dressing for acute burns, intermediate treatment prior to skin grafting, bolster for skin autografts, dressing for integration of dermal substitutes, dressing for skin graft donor sites, and integrated dressing in large burns. RESULTS: Fifteen studies met our inclusion criteria. One study showed negative pressure wound therapy improved perfusion in acute partial-thickness burns, 8 out of 9 studies showed benefits when used as a skin graft bolster dressing, 1 out of 2 studies showed improved rate of revascularization when used over dermal substitutes, and 1 study showed increased rate of re-epithelialization when used over skin graft donor sites. CONCLUSIONS: Negative pressure can improve autograft take when used as a bolster dressing. There is limited data to suggest that it may also improve the rate of revascularization of dermal substitutes and promote re-epithelialization of skin graft donor sites. Other uses suggested by studies that did not meet our inclusion criteria include improving vascularity in acute partial-thickness burns and as an integrated dressing for the management of large burns. Further studies are warranted for most clinical applications to establish negative pressure as an effective adjunct in burn wound care. PMID- 27378362 TI - Increased cell proliferation and neural activity by physostigmine in the telencephalon of adult zebrafish. AB - Physostigmine, an acetylcholinesterase inhibitor, is known to affect the brain function in various aspects. This study was conducted to test whether physostigmine affects cell proliferation in the telencephalon of zebrafish. BrdU labeled cells was prominently observed in the ventral zone of the ventral telencephalon of zebrafish. The increased number of BrdU- and proliferating cell nuclear antigen-labeled cells were shown in zebrafish treated with 200MUM physostigmine, which was inhibited by pretreatment with 200MUM scopolamine. iNOS mRNA expression was increased in the brain of zebrafish treated with 200MUM physostigmine. Consistently, aminoguanidine, an iNOS inhibitor, attenuated the increase in the number of BrdU-labeled cells by physostigmine treatment. Zebrafish also showed seizure-like locomotor activity characterized by a rapid and abrupt movement during a 30min treatment with 200MUM physostigmine. Neural activity in response to an electrical stimulus was increased in the isolated telencephalon of zebrafish continuously perfused with 200MUM physostigmine. None of the number of BrdU-labeled cells, neural activity, or locomotor activity was affected by treatment with 20MUM physostigmine. These results suggest that 200MUM physostigmine increased neural activity and induced cell proliferation via nitric oxide production in zebrafish. PMID- 27378364 TI - The missing link: introducing travel medicine into the undergraduate medical curriculum. PMID- 27378363 TI - Association between plasma lipoprotein levels and bioprosthetic valve structural degeneration. AB - INTRODUCTION: Structural valve degeneration (SVD) leads to the failure of aortic valve bioprostheses. It is suspected that lipid-derived factors could play a role in SVD. We hypothesised that oxidised low-density lipoprotein (OxLDL), OxLDL/LDL, OxLDL/high-density lipoprotein (OxLDL/HDL) and proprotein convertase subtilisin/kexin 9 (PCSK9) may be associated with SVD. METHODS: We included 199 patients who underwent an aortic valve replacement with a bioprosthesis and had an echocardiography follow-up to evaluate the function of the prosthesis. SVD was defined as an increase in mean transprosthetic gradient (>=10 mm Hg) or a worsening of transprosthetic regurgitation (>=1/3) during the follow-up. RESULTS: After a mean follow-up of 8+/-3.5 years, 41(21%) patients developed SVD. The univariate predictors of SVD were LDL (p=0.03), apolipoprotein B (p=0.01), OxLDL (p=0.02), OxLDL/HDL (p=0.009) and LDL associated with small, dense particles (LDL C<255A) (p=0.02). In a model adjusted for covariates, only OxLDL/HDL (OR 1.49, 95%CI 1.08 to 2.07 per 10 units, p=0.01) remained associated with SVD. There was a significant interaction between OxLDL/HDL and PCSK9 on SVD (p=0.05). After adjustment, compared with patients with low OxLDL/HDL (median, <25.4) and low PCSK9 (median, <298 ng/mL) (referent), patients with both an elevated OxLDL/HDL ratio and PCSK9 had a higher risk of SVD (OR 2.93, 95% CI 1.02 to 9.29, p=0.04). CONCLUSIONS: OxLDL/HDL ratio is independently associated with SVD. PMID- 27378365 TI - Travel medicine education-what are the needs? PMID- 27378366 TI - Varicella outbreak in Sudanese refugees from Calais. AB - We describe an outbreak of varicella in 31 Sudanese refugees (all except one were male, mean age: 26 +/- 1), from the Calais migrant camp and sheltered in a French transit area. The attack rate was 39%. Adults are scantly immunized against varicella zoster virus in East Africa and may be exposed to epidemics once in France. PMID- 27378367 TI - A comparison of compliance rates with anti-vectorial protective measures during travel to regions with dengue or chikungunya activity, and regions endemic for Plasmodium falciparum malaria. AB - BACKGROUND: There is limited information on compliance rates with anti-vectorial protective measures (AVPMs) during travel to countries with risk of dengue and chikungunya. We evaluated differences in mosquito exposures, and factors associated with AVPM compliance in travellers going to countries where the principal mosquito-borne infectious disease threat is falciparum malaria and those where risk of dengue or chikungunya predominates. METHODS: Department of Defence beneficiaries with planned travel to regions where the predominant mosquito-borne infection is falciparum malaria, and those with predominantly dengue or chikungunya risk, were included. Regions were divided into three groups: 'high-risk falciparum malaria', 'low-risk falciparum malaria' and 'chikungunya/dengue risk'. Demographics, trip characteristics, arthropod exposure and AVPM compliance were captured using pre- and post-travel surveys. Skin repellent compliance was defined as self-reported use, categorized as 'often/every day'. A logistic regression model was used to estimate factors associated with AVPM compliance. RESULTS: 183 (9%), 185 (9%) and 149 (7%) travelled to high and low falciparum malaria risk regions, and chikungunya/dengue risk regions, respectively. Overall, 53% (95% CI: 48-57%) and 16% (95% CI: 12 19%) were compliant with repellent use on skin and clothing, respectively. Daytime bites were reported more frequently in chikungunya/dengue risk regions than high malaria risk regions (37% vs. 10%), while night time bites were frequently in high malaria risk regions (53% vs 20%; P < 0.001). Compliance with skin repellents was associated with female gender [RR: 1.54 (95% CI: 1.05-2.28)], observing mosquitoes during travel [RR: 2.77 (95% CI: 1.76-4.36)] and travel during the rainy season [RR: 2.45 (95% CI: 1.66-3.71)]). CONCLUSIONS: Poor AVPM compliance was observed in the overall cohort. Compliance with skin repellent use was associated with female gender, observing mosquitoes and travelling during the rainy season, and was not associated with the risk of malaria or chikungunya/dengue at the travel destination. PMID- 27378368 TI - Travelers lowering their guard: a bacterial, viral and protozoan co-infection after a five-day journey in India. AB - We present a case of concurrent infections by Campylobacter jejuni, Giardia intestinalis and Hepatitis E virus acquired during a 5-days travel to India by an Italian traveller : Professionals responsible for pre- and post-travel care should underline food and water precautions and prescribe an adequate diagnostic work-up in symptomatic patients. PMID- 27378369 TI - Adverse event reports following yellow fever vaccination, 2007-13. AB - BACKGROUND: Yellow fever (YF) vaccines have been available since the 1930s and are generally considered safe and effective. However, rare reports of serious adverse events (SAE) following vaccination have prompted the Advisory Committee for Immunization Practices to periodically expand the list of conditions considered contraindications and precautions to vaccination. METHODS: We describe adverse events following YF vaccination reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) from 2007 through 2013 and calculate age- and sex specific reporting rates of all SAE, anaphylaxis, YF vaccine-associated neurologic disease (YEL-AND) and YF vaccine-associated viscerotropic disease (YEL AVD). RESULTS: There were 938 adverse events following YF vaccination reported to VAERS from 2007 through 2013. Of these, 84 (9%) were classified as SAEs for a rate of 3.8 per 100 000 doses distributed. Reporting rates of SAEs increased with increasing age with a rate of 6.5 per 100 000 in persons aged 60-69 years and 10.3 for >=70 years. The reporting rate for anaphylaxis was 1.3 per 100 000 doses distributed and was highest in persons <=18 years (2.7 per 100 000). Reporting rates of YEL-AND and YEL-AVD were 0.8 and 0.3 per 100 000 doses distributed, respectively; both rates increased with increasing age. CONCLUSIONS: These findings reinforce the generally acceptable safety profile of YF vaccine, but highlight the importance of continued physician and traveller education regarding the risks and benefits of YF vaccination, particularly for older travellers. PMID- 27378370 TI - Early detection of Zika virus infection among travellers from areas of ongoing transmission in China. AB - Nine imported Zika virus (ZIKV) infections (four through temperature monitoring and epidemiological investigation at entry and five by active surveillance tracking of index case contacts during follow-up; from Venezuela [n = 5], Samoa [n = 3] and both Samoa and Fiji [n = 1]) were detected in mainland China from February 1 to 29, 2016. The minimal incubation period lasted 5.2 days, with mean lag time to diagnosis of 2.6 days. Diagnosis relied on positive real-time reverse transcriptase polymerase chain reaction for ZIKV RNA in serum (n = 7), urine (n = 4) or saliva (n = 3), respectively. All cases recovered rapidly without serious complications. PMID- 27378371 TI - Pupil diameter changes reflect difficulty and diagnostic accuracy during medical image interpretation. AB - BACKGROUND: No automated methods exist to objectively monitor and evaluate the diagnostic process while physicians review computerized medical images. The present study tested whether using eye tracking to monitor tonic and phasic pupil dynamics may prove valuable in tracking interpretive difficulty and predicting diagnostic accuracy. METHODS: Pathologists interpreted digitized breast biopsies varying in diagnosis and rated difficulty, while pupil diameter was monitored. Tonic diameter was recorded during the entire duration of interpretation, and phasic diameter was examined when the eyes fixated on a pre-determined diagnostic region during inspection. RESULTS: Tonic pupil diameter was higher with increasing rated difficulty levels of cases. Phasic diameter was interactively influenced by case difficulty and the eventual agreement with consensus diagnosis. More difficult cases produced increases in pupil diameter, but only when the pathologists' diagnoses were ultimately correct. All results were robust after adjusting for the potential impact of screen brightness on pupil diameter. CONCLUSIONS: Results contribute new understandings of the diagnostic process, theoretical positions regarding locus coeruleus-norepinephrine system function, and suggest novel approaches to monitoring, evaluating, and guiding medical image interpretation. PMID- 27378373 TI - Anticonvulsant effect of a ghrelin receptor agonist in 6Hz corneally kindled mice. AB - Ghrelin has anticonvulsant and neuroprotective effects in models of chemoconvulsant-induced seizures and status epilepticus. In this study we investigated whether deletion of the ghrelin receptor could alter the kindling process in the 6 Hz corneal kindling model and whether ghrelin receptor ligands possess anticonvulsant effects in fully kindled mice. Ghrelin receptor wild-type and knockout mice were electrically stimulated at a subconvulsive current twice daily via corneal electrodes until they reached the fully kindled state. Mice lacking the ghrelin receptor showed similar seizure severity during kindling acquisition as well as in the maintenance phase when compared to their wild-type littermates. Subsequently we proceeded by investigating possible anticonvulsant effects of the ghrelin receptor ligands in the acute 6 Hz seizure model and the fully 6 Hz kindled mice. The ghrelin receptor agonist JMV-1843 decreased the seizure severity score both in acutely 6 Hz stimulated mice and in fully kindled ghrelin receptor wild-type mice, but not in fully kindled ghrelin receptor knockout mice. No effect on seizure severity was observed following the ghrelin receptor antagonist JMV-2959 in both models. This finding indicates that JMV-1843 exerts an anticonvulsant effect in kindled mice via the ghrelin receptor. PMID- 27378372 TI - Context dependent regulatory patterns of the androgen receptor and androgen receptor target genes. AB - BACKGROUND: Expression of the androgen receptor (AR) is associated with androgen dependent proliferation arrest and terminal differentiation of normal prostate epithelial cells. Additionally, activation of the AR is required for survival of benign luminal epithelial cells and primary cancer cells, thus androgen deprivation therapy (ADT) leads to apoptosis in both benign and cancerous tissue. Escape from ADT is known as castration-resistant prostate cancer (CRPC). In the course of CRPC development the AR typically switches from being a cell-intrinsic inhibitor of normal prostate epithelial cell proliferation to becoming an oncogene that is critical for prostate cancer cell proliferation. A clearer understanding of the context dependent activation of the AR and its target genes is therefore desirable. METHODS: Immortalized human prostate basal epithelial EP156T cells and progeny cells that underwent epithelial to mesenchymal transition (EMT), primary prostate epithelial cells (PrECs) and prostate cancer cell lines LNCaP, VCaP and 22Rv1 were used to examine context dependent restriction and activation of the AR and classical target genes, such as KLK3. Genome-wide gene expression analyses and single cell protein analyses were applied to study the effect of different contexts. RESULTS: A variety of growth conditions were tested and found unable to activate AR expression and transcription of classical androgen-dependent AR target genes, such as KLK3, in prostate epithelial cells with basal cell features or in mesenchymal type prostate cells. The restriction of androgen- and AR-dependent transcription of classical target genes in prostate basal epithelial cells was at the level of AR expression. Exogenous AR expression was sufficient for androgen-dependent transcription of AR target genes in prostate basal epithelial cells, but did not exert a positive feedback on endogenous AR expression. Treatment of basal prostate epithelial cells with inhibitors of epigenetic gene silencing was not efficient in inducing androgen-dependent transcription of AR target genes, suggesting the importance of missing cofactor(s). CONCLUSIONS: Regulatory mechanisms of AR and androgen-dependent AR target gene transcription are insufficiently understood and may be critical for prostate cancer initiation, progression and escape from standard therapy. The present model is useful for the study of context dependent activation of the AR and its transcriptome. PMID- 27378375 TI - Taking personal responsibility: Nurses' and assistant nurses' experiences of good nursing practice in psychiatric inpatient care. AB - Therapeutic nurse-patient relationships are considered essential for good nursing practice in psychiatric inpatient care. Previous research suggests that inpatient care fails to fulfil patients' expectations in this regard, and that nurses might experience the reality of inpatient care as an obstruction. The aim of the present study was to explore nurses' and assistant nurses' experiences of good nursing practice in the specific context of psychiatric inpatient care. Qualitative interviews were conducted with 12 skilled, relationship-oriented nurses and assistant nurses in order to explore their experiences with nursing practice related to psychiatric inpatient care. Interviews were transcribed and analysed using an interpretive descriptive approach. Findings describe good nursing practice as a matter of nurses and assistant nurses taking personal responsibility for their actions and for the individual patient as a person. Difficulties in providing dignified nursing care and taking personal responsibility cause them to experience feelings of distress and frustration. Shared values and nursing leadership supports being moral and treating patients with respect, having enough time supports being present and connecting with patients, and working as a part of a competent team with critical daily discussions and diversity supports being confident and building trust. The findings suggest that taking personal responsibility is integral to good nursing practice. If unable to improve poor circumstances, nurses might be forced to promote their own survival by refuting or redefining their responsibility. Nurses need to prioritize being with patients and gain support in shaping their own nursing practice. Nursing leadership should provide moral direction and defend humanistic values. PMID- 27378376 TI - The dual anti-inflammatory and antioxidant activities of natural honey promote cell proliferation and neural regeneration in a rat model of colitis. AB - A decreased antioxidant capacity and excessive inflammation are well-known features in the pathogenesis of ulcerative colitis (UC). Recent evidence has suggested a role of honey in reducing colitis-induced inflammatory and oxidative stress markers. In this study, we examined whether the anti-inflammatory and anti oxidative properties of honey have a beneficial effect on the enteric innervation and cellular proliferation of UC in rat. The colitis was induced in rats by dextran sodium sulphate (DSS). The effect of natural honey on induced colitis was assessed by the following parameters in colonic samples: tissue injury, inflammatory infiltration, interleukin-1beta and -6, superoxide dismutase and reduced glutathione. In addition, the expression of tumour necrosis factor-alpha, inducible NO synthase, caspase-3, CD34, Ki67, S100, c-kit, and neuron-specific enolase were examined by immunohistochemistry. Compared to the DSS-induced colitis group, the honey-treated group had significantly improved macroscopic and microscopic scores and exhibited the down-regulation of oxidative, inflammatory, and apoptotic markers. In addition, up-regulation of intrinsic muscular innervation and epithelial cellular proliferation markers was detected. These results provide new insight into the beneficial role of natural honey in the treatment of DSS-induced colitis via the inhibition of colonic motor dysfunction and the inflammatory-oxidative-apoptotic cascade. In addition, the role of honey in epithelial regeneration was clarified. PMID- 27378374 TI - Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses. AB - The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ~4,900 RNAs enriched for GGUA motifs in adult mouse brains. TAF15 and FUS exhibit similar binding patterns in introns, are enriched in 3' untranslated regions and alter genes distinct from TDP-43. However, unlike FUS and TDP-43, TAF15 has a minimal role in alternative splicing. In human neural progenitors, TAF15 and FUS affect turnover of their RNA targets. In human stem cell-derived motor neurons, the RNA profile associated with concomitant loss of both TAF15 and FUS resembles that observed in the presence of the ALS-associated mutation FUS R521G, but contrasts with late-stage sporadic ALS patients. Taken together, our findings reveal convergent and divergent roles for FUS, TAF15 and TDP-43 in RNA metabolism. PMID- 27378377 TI - Immunotoxicity of skin acid secretion produced by the sea slug Berthellina citrina in mice spleen: Histological and Immunohistochemical study. AB - Acid secretion containing sulfuric and hydrochloric acids is a fascinating defensive phenomenon within many groups of marine organisms. This study aimed to investigate the mice spleen histology and immunotoxicity using skin acid secretion (SAS) of the sea slug Berthellina citrina after oral administration. The spleen showed atrophy in the white pulp, decrease in the splenocytes density, megakaryocytes cytoplasmic degeneration as well as inflammatory cells infiltrations. The white and red pulp splenocytes number decreased time dependently in the treated spleens. Additionally, the size of the megakaryocytes increased as compared with the control. The administration with SAS increased the number of the IgA(+) cells aggregation in the splenic red pulp. Furthermore, after 7days of the administration, large number of dispersed IgA(+) cells were distributed in splenic parenchyma. The IgA(+) cells numbers increased time dependently as compared with those in the control. The aggregation sizes and number of the F4/80(+) cell in the splenic red pulp were increased. Furthermore the F4/80(+) cells numbers increased time-dependently as compared with those in the control. The UEAI(+) cells were found as free cells but not in aggregations in the control splenic red pulp. Contradictory to the number of IgA(+) cells and F4/80(+) cells the number of the UEAI(+) cells decreased time-dependently after administration with SAS. Hematologically, abnormal numbers of WBCs different cells were observed after administration with SAS. This study provides new insight about the toxicity of a marine extract may be used in natural products industry or medical applications. PMID- 27378378 TI - Has gene duplication impacted the evolution of Eutherian longevity? AB - One of the greatest unresolved questions in aging biology is determining the genetic basis of interspecies longevity variation. Gene duplication is often the key to understanding the origin and evolution of important Eutherian phenotypes. We systematically identified longevity-associated genes in model organisms that duplicated throughout Eutherian evolution. Longevity-associated gene families have a marginally significantly higher rate of duplication compared to non longevity-associated gene families. Anti-longevity-associated gene families have significantly increased rate of duplication compared to pro-longevity gene families and are enriched in neurodegenerative disease categories. Conversely, duplicated pro-longevity-associated gene families are enriched in cell cycle genes. There is a cluster of longevity-associated gene families that expanded solely in long-lived species that is significantly enriched in pathways relating to 3-UTR-mediated translational regulation, metabolism of proteins and gene expression, pathways that have the potential to affect longevity. The identification of a gene cluster that duplicated solely in long-lived species involved in such fundamental processes provides a promising avenue for further exploration of Eutherian longevity evolution. PMID- 27378379 TI - Time Economical Total Synthesis of (-)-Oseltamivir. AB - A time economical 60 min total synthesis of (-)-oseltamivir was accomplished in a single reaction vessel over five steps. One of the key issues is reduction in the number of steps by eliminating lengthy reaction steps with substitution of a rapid epimerization step. A catalytic system consisting of three reagents, namely, diphenylprolinol silyl ether, thiourea, and acid, was developed for a rapid asymmetric Michael reaction with excellent diastereo- and enantioselectivities. All reactions were optimized in terms of not only yield and selectivity but also reaction time. PMID- 27378382 TI - Recent advances in the template-directed synthesis of porphyrin nanorings. AB - The template-directed strategy is a powerful method to construct porphyrin nanorings with high complexities, wherein metalloporphyrin precursors pre organize via supramolecular interactions of the porphyrin or its central metal with a carefully selected template, and then react with each other to deliver a final cyclic multiporphyrin structure. In this article, we review the recent breakthroughs in the template-directed synthesis methods and new structures of porphyrin or metalloporphyrin nanorings, as well as their applications in host guest chemistry and artificial light-harvesting. PMID- 27378380 TI - Worry about recurrence in a multi-ethnic population of breast cancer survivors and their partners. AB - PURPOSE: The objectives of this study are to describe racial/ethnic differences and clinical/treatment correlates of worry about recurrence and examine modifiable factors in the health care experience to reduce worry among breast cancer survivors, partners, and pairs. METHODS: Women with non-metastatic breast cancer identified by the Detroit and Los Angeles SEER registries between 6/05 and 2/07 were surveyed at 9 months and 4 years. Latina and Black women were oversampled. Partners were surveyed at time 2. Worry about recurrence was regressed on sociodemographics, clinical/treatment, and modifiable factors (e.g., emotional support received by providers) among survivors, partners, and pairs. RESULTS: The final sample included 510 pairs. Partners reported more worry about recurrence than survivors. Compared to Whites, Latinas(os) were more likely to report worry and Blacks were less likely to report worry (all p < 0.05). Partners of survivors who received chemotherapy reported more worry (OR = 2.47 [1.45, 4.22]). Among modifiable factors, survivors and pairs who received more emotional support from providers were less likely to report worry than those survivors and pairs who did not receive such support (OR = 0.56 [0.32, 0.97]) and (OR = 0.45 [0.23,0.85]), respectively. CONCLUSIONS: Early identification of survivors and partners who are reporting considerable worry about recurrence can lead to targeted culturally sensitive interventions to avoid poorer outcomes. Interventions focused on health care providers offering information on risk and emotional support to survivors and partners is warranted. PMID- 27378381 TI - The 14th Ile residue is essential for Leptin function in regulating energy homeostasis in rat. AB - LEPTIN (LEP) is a circulating hormone released primarily from white adipocytes and is crucial for regulating satiety and energy homeostasis in humans and animals. Using the CRISPR technology, we created a set of Lep mutant rats that carry either null mutations or a deletion of the 14(th) Ile (LEP(?I14)) in the mature LEP protein. We examined the potential off-target sites (OTS) by whole genome high-throughput sequencing and/or Sanger-sequencing analysis and found no OTS in mutant rats. Mature LEP(?I14) is incessantly produced and released to blood at a much elevated level due to the feedback loop. Structure modeling of binding conformation between mutant LEP(?I14) and LEPTIN receptor (LEPR) suggests that the conformation of LEP(?I14) impairs its binding with LEPR, consistent with its inability to activate STAT3-binding element in the luciferase reporter assay. Phenotypic study demonstrated that Lep(?I14) rats recapitulate phenotypes of Lep null mutant rats including obesity, hyperinsulinemia, hepatic steatosis, nephropathy, and infertility. Compared to the existing ob/ob mouse models, this Lep(?I14/?I14) rat strain provides a robust tool for further dissecting the roles of LEP in the diabetes related kidney disease and reproduction problem, beyond its well established function in regulating energy homeostasis. PMID- 27378385 TI - Electrocardiographic findings during balloon angioplasty of the left circumflex coronary artery - influence of location of the ischemic segments with respect to the obtuse margin of the left ventricle. AB - BACKGROUND: Acute left circumflex coronary artery (LCx) occlusion is not easily detected by the standard 12-lead electrocardiogram (ECG). METHODS: In 16 patients continuous ECG recording was performed during balloon occlusion. The treated lesions were divided into proximal and distal based on the location of the ischemic segments with respect to the left obtuse margin of the heart. RESULTS: Mean DeltaST (=ST amplitude during inflation - pre-inflation ST) >=0.5mm in both leads I and aVL predicted a proximal occlusion site with sensitivity of 62.5% (95% confidence interval [CI] 24.9-91.5%), specificity 100% (95% CI 63.1-100%), positive predictive value 100% (95% CI 47.8-100%), and negative predictive value 72.7% (95% CI 39-94%). In lead III, mean DeltaST was +0.3mm in the distal and 0.2mm in the proximal group, respectively (p=0.036). CONCLUSIONS: ST elevation in leads I and aVL is associated with myocardial ischemia at or proximal to the left obtuse margin. PMID- 27378383 TI - Evaluation of the biomarker candidate MFAP4 for non-invasive assessment of hepatic fibrosis in hepatitis C patients. AB - BACKGROUND: The human microfibrillar-associated protein 4 (MFAP4) is located to extracellular matrix fibers and plays a role in disease-related tissue remodeling. Previously, we identified MFAP4 as a serum biomarker candidate for hepatic fibrosis and cirrhosis in hepatitis C patients. The aim of the present study was to elucidate the potential of MFAP4 as biomarker for hepatic fibrosis with a focus on the differentiation of no to moderate (F0-F2) and severe fibrosis stages and cirrhosis (F3 and F4, Desmet-Scheuer scoring system). METHODS: MFAP4 levels were measured using an AlphaLISA immunoassay in a retrospective study including n = 542 hepatitis C patients. We applied a univariate logistic regression model based on MFAP4 serum levels and furthermore derived a multivariate model including also age and gender. Youden-optimal cutoffs for binary classification were determined for both models without restrictions and considering a lower limit of 80 % sensitivity (correct classification of F3 and F4), respectively. To assess the generalization error, leave-one-out cross validation (LOOCV) was performed. RESULTS: MFAP4 levels were shown to differ between no to moderate fibrosis stages F0-F2 and severe stages (F3 and F4) with high statistical significance (t test on log scale, p value <2.2.10(-16)). In the LOOCV, the univariate classification resulted in 85.8 % sensitivity and 54.9 % specificity while the multivariate model yielded 81.3 % sensitivity and 61.5 % specificity (restricted approaches). CONCLUSIONS: We confirmed the applicability of MFAP4 as a novel serum biomarker for assessment of hepatic fibrosis and identification of high-risk patients with severe fibrosis stages in hepatitis C. The combination of MFAP4 with existing tests might lead to a more accurate non invasive diagnosis of hepatic fibrosis and allow a cost-effective disease management in the era of new direct acting antivirals. PMID- 27378384 TI - Cyclic di-AMP targets the cystathionine beta-synthase domain of the osmolyte transporter OpuC. AB - Cellular turgor is of fundamental importance to bacterial growth and survival. Changes in external osmolarity as a consequence of fluctuating environmental conditions and colonization of diverse environments can significantly impact cytoplasmic water content, resulting in cellular lysis or plasmolysis. To ensure maintenance of appropriate cellular turgor, bacteria import ions and small organic osmolytes, deemed compatible solutes, to equilibrate cytoplasmic osmolarity with the extracellular environment. Here, we show that elevated levels of c-di-AMP, a ubiquitous second messenger among bacteria, result in significant susceptibility to elevated osmotic stress in the bacterial pathogen Listeria monocytogenes. We found that levels of import of the compatible solute carnitine show an inverse correlation with intracellular c-di-AMP content and that c-di-AMP directly binds to the CBS domain of the ATPase subunit of the carnitine importer OpuC. Biochemical and structural studies identify conserved residues required for this interaction and transport activity in bacterial cells. Overall, these studies reveal a role for c-di-AMP mediated regulation of compatible solute import and provide new insight into the molecular mechanisms by which this essential second messenger impacts bacterial physiology and adaptation to changing environmental conditions. PMID- 27378386 TI - BEACON: A Summary Framework to Overcome Potential Reimbursement Hurdles. AB - OBJECTIVE: To provide a framework for addressing payers' criteria during the development of pharmaceuticals. METHODS: A conceptual framework was presented to an international health economic expert panel for discussion. A structured literature search (from 2010 to May 2015), using the following databases in Ovid: Medline((r)) and Medline((r)) In-Process (PubMed), Embase (Ovid), EconLit (EBSCOhost) and the National Health Service Economic Evaluation Database (NHS EED), and a 'grey literature' search, were conducted to identify existing criteria from the payer perspective. The criteria assessed by existing frameworks and guidelines were collated; the most commonly reported criteria were considered for inclusion in the framework. A mnemonic was conceived as a memory aide to summarise these criteria. RESULTS: Overall, 41 publications were identified as potentially relevant to the objective. Following further screening, 26 were excluded upon full-text review on the basis of no framework presented (n = 13), redundancy (n = 11) or abstract only (n = 2). Frameworks that captured criteria developed for or utilised by the pharmaceutical industry (n = 5) and reimbursement guidance (n = 10) were reviewed. The most commonly identified criteria-unmet need/patient burden, safety, efficacy, quality-of-life outcomes, environment, evidence quality, budget impact and comparator-were incorporated into the summary framework. For ease of communication, the following mnemonic was developed: BEACON (Burden/target population, Environment, Affordability/value, Comparator, Outcomes, Number of studies/quality of evidence). CONCLUSIONS: The BEACON framework aims to capture the 'essence' of payer requirements by addressing the most commonly described criteria requested by payers regarding the introduction of a new pharmaceutical. PMID- 27378387 TI - Geochemical disturbance of soil cover in the nonferrous mining centers of the Selenga River basin. AB - The anthropogenic geochemical transformation of soil cover in large nonferrous mining centers of the Selenga River basin was assessed. The results of the geochemical survey of 2010-2012 revealed the spatial distribution patterns and abundances of 18 hazardous heavy metals and metalloids in the soils of Erdenet (Mongolia) and Zakamensk (Buryat republic, Russian Federation). In both cities, mining activities disturbed soil cover which accumulates Mo, Cu, As, Sb, W in Erdenet and Bi, W, Cd, Be, Pb, Mo, Sb in Zakamensk. Maximum accumulation of elements in Erdenet is restricted to the industrial zone. In Zakamensk, it has spread on 1/2 of the territory with the degree of multielemental pollution exceeding the extremely dangerous level by 16 times. The effect of mining centers on the state of the river system is local and does not spread to the Selenga River. Downstream from Erdenet, an artificial pool intercepts heavy metal and metalloid flows of the Erdenetii-Gol River. By contrast, downstream from the tailing dumps of the Dzhida tungsten-molybdenum plant the concentrations of ore elements W and Mo and their accessories Bi and Cd in the Modonkul River exceed background values by 146, 20, 57, and 21 times, respectively, decreasing by an order of magnitude 30 km downstream. PMID- 27378388 TI - Vascular laminins in physiology and pathology. PMID- 27378389 TI - Arthroscopic Central Acetabular Decompression: Clinical Outcomes at Minimum 2 Year Follow-up Using a Matched-Pair Analysis. AB - PURPOSE: To assess 2-year clinical outcomes of patients who underwent hip arthroscopy for central acetabular osteophytes (CAO) treated with central acetabular decompression (CAD), and to compare these outcomes with those of a matched control group. METHODS: Data were prospectively gathered for patients undergoing CAD during hip arthroscopy from February 2008 to July 2012. All patients were assessed pre- and postoperatively at 3 months, 1 year, and 2 years with modified Harris Hip Score, Non-Arthritic Hip Score, Hip Outcome Score Activities of Daily Living, Hip Outcome Score-Sport-Specific Subscale, and visual analog scale (VAS) for pain. Patient satisfaction (0 to 10) was collected. A matched control group of patients without CAOs who did not undergo CAD was selected on a 1:3 ratio. RESULTS: Forty-nine hips were included in the CAD group and 147 in the control group. The mean change in patient-reported outcome (PRO) scores at 2-year follow-up in the CAD group for modified Harris Hip Score, Hip Outcome Score-Activities of Daily Living, Hip Outcome Score-Sport-Specific Subscale, Non-Arthritic Hip Score, and VAS was 11.0, 19.6, 15.2, 21.4, and -2, respectively. The mean change in PRO scores at 2-year follow-up in the control group was 17.0, 19.8, 24.0, 20.9, and -2.75, respectively. All improvements in PRO scores for both groups were statistically significant compared with the data collected preoperatively (P < .001). There was no statistically significant difference in postoperative PRO scores and VAS between the groups. Postoperative patient satisfaction at the latest follow-up was 7.14 and 7.60 for CAD and control groups, respectively. CONCLUSIONS: This study showed that patients with a CAO treated with CAD during hip arthroscopy had favorable outcomes at minimum 2 years postoperatively. Furthermore, the study group showed similar PRO scores and VAS to the control group. We conclude that CAD is a viable treatment option for CAO, yielding clinical improvement at short-term follow-up. LEVEL OF EVIDENCE: Level III, prospective comparative study. PMID- 27378390 TI - Decarboxylative Csp(3)-Csp(3) coupling for benzylation of unstable ketone enolates: synthesis of p-(acylethyl)phenols. AB - A new decarboxylative Csp(3)-Csp(3) coupling approach for the benzylation of ketone enolates has been developed. A variety of raspberry ketone derivatives were conveniently synthesized in good to excellent yields under mild conditions. A crossover reaction shed light on the mechanism of this tandem reaction. PMID- 27378392 TI - Development of a room laser based real-time alignment monitoring system using an array of photodiodes. AB - PURPOSE: To develop a real-time alignment monitoring system (RAMS) to compensate for the limitations of the conventional room-laser-based alignment system. To verify the feasibility of the RAMS, reproducibility and accuracy tests were conducted. METHODS: RAMS was composed of a room laser sensing array (RLSA), an electric circuit, an analog-to-digital converter (ADC), and a control PC. The RLSA was designed to arrange photodiodes in a pattern that results in the RAMS having a resolution of 1mm. The photodiodes were used for quantitative assessment of the alignment condition. To verify the usability of the developed system, we conducted tests of temporal reproducibility, repeatability, and accuracy. RESULTS: The results of the temporal reproducibility test suggested that the signal of the RAMS was stable with respect to time. Further, the repeatability test resulted in a maximum coefficient of variance of 1.14%, suggesting that the signal of the RAMS was stable over repeated set-ups. The accuracy test confirmed that the "on" and "off" signals could be distinguished by signal intensity, considering that the "off" signal was below 75% of the "on" signal in every case. In addition, we confirmed that the system can detect 1mm of movement by monitoring the pattern of the "on" and "off" signals. CONCLUSION: We developed a room laser based alignment monitoring system. The feasibility test verified that the system is capable of quantitative alignment monitoring in real time. We expect that the RAMS can propose the potential of the room laser based alignment monitoring method. PMID- 27378391 TI - Nanoconjugation prolongs endosomal signaling of the epidermal growth factor receptor and enhances apoptosis. AB - It is becoming increasingly clear that intracellular signaling can be subject to strict spatial control. As the covalent attachment of a signaling ligand to a nanoparticle (NP) impacts ligand-receptor binding, uptake, and trafficking, nanoconjugation provides new opportunities for manipulating intracellular signaling in a controlled fashion. To establish the effect of nanoconjugation on epidermal growth factor (EGF) mediated signaling, we investigate here the intracellular fate of nanoconjugated EGF (NP-EGF) and its bound receptor (EGFR) by quantitative correlated darkfield/fluorescence microscopy and density-based endosomal fractionation. We demonstrate that nanoconjugation prolongs the dwell time of phosphorylated receptors in the early endosomes and that the retention of activated EGFR in the early endosomes is accompanied by an EGF mediated apoptosis at effective concentrations that do not induce apoptosis in the case of free EGF. Overall, these findings indicate nanoconjugation as a rational strategy for modifying signaling that acts by modulating the temporo-spatial distribution of the activated EGF-EGFR ligand-receptor complex. PMID- 27378393 TI - The medical physics specialization system in Poland. AB - This paper presents the situation of the profession of medical physicists in Poland. The official recognition of the profession of medical physicist in Polish legislation was in 2002. In recent years, more and more Universities which have Physics Faculties introduce a medical physics specialty. At present, there are about 15 Universities which offer such programmes. These Universities are able to graduate about 150 medical physicists per year. In 2002, the Ministry of Health introduced a programme of postgraduate specialization in medical physics along the same rules employed in the specialization of physicians in various branches of medicine. Five institutions, mostly large oncology centres, were selected as teaching institutions, based on their experience, the quality of the medical physics professionals, staffing levels, equipment availability, lecture halls, etc. The first cycle of the specialization programme started in 2006, and the first candidates completed their training at the end of 2008, and passed their official state exams in May 2009. As of January 2016, there are 196 specialized medical physicists in Poland. Another about 120 medical physicists are undergoing specialization. The system of training of medical physics professionals in Poland is well established. The principles of postgraduate training and specialization are well defined and the curriculum of the training is very demanding. The programme of specialization was revised in 2011 and is in accordance with EC and EFOMP recommendations. PMID- 27378394 TI - Highly fluorescent resorcinarene cavitand nanocapsules with efficient renal clearance. AB - Nanomaterial based imaging approaches hold substantial promise in addressing current diagnostic and therapeutic challenges. One of the key requirements for the successful clinical translation of nanomaterials is their complete clearance from the body within a reasonable time period preferably via the renal filtration route. This article describes the synthesis of highly fluorescent, water soluble, resorcinarene cavitand nanocapsules and demonstrates their effective renal clearance in mice. The synthesis and functionalization of nanocapsules was accomplished in a one-pot operation via thiol-ene reactions without involving self-assembly, sacrificial templates or emulsions. Water soluble resorcinarene cavitand nanocapsules obtained by this approach were covalently functionalized with Alexa Fluor 750. Highly fluorescent nanocapsules with hydrodynamic diameters of 122 nm and 68 nm and extinction coefficients of 1.3 * 10(9) M(-1) cm(-1) and 1.5 * 10(8) M(-1) cm(-1) respectively were prepared by varying the reaction conditions. The in vivo biodistribution and clearance of these nanocapsules in mice followed by whole-body fluorescence imaging showed that they were both cleared renally within a few hours. Given the inherent encapsulation capabilities of nanocapsules, the renal clearance demonstrated in this work opens up new opportunities for their theranostic applications especially for targeting and treating the urinary tract. PMID- 27378395 TI - Inhibition of transglutaminase 2 reduces efferocytosis in human macrophages: Role of CD14 and SR-AI receptors. AB - BACKGROUND AND AIMS: Transglutaminase 2 (TGM2), a member of the transglutaminase family of enzymes, is a multifunctional protein involved in numerous events spanning from cell differentiation, to signal transduction, apoptosis, and wound healing. It is expressed in a variety of cells, macrophages included. Macrophage TGM2 promotes the clearance of apoptotic cells (efferocytosis) and emerging evidence suggests that defective efferocytosis contributes to the consequences of inflammation-associated diseases, including atherosclerotic lesion progression and its sequelae. Of interest, active TGM2 identified in human atherosclerotic lesions plays critical roles in plaque stability through effects on matrix cross linking and TGFbeta activity. This study explores the mechanisms by which TGM2 controls efferocytosis in human macrophages. METHODS AND RESULTS: Herein we show that TGM2 increases progressively during monocyte differentiation towards macrophages and controls their efferocytic potential as well as morphology and viability. Two experimental approaches that took advantage of the inhibition of TGM2 activity and protein silencing give proof that TGM2 reduction significantly impairs macrophage efferocytosis. Among the mechanisms involved we highlighted a role of the receptors CD14 and SR-AI whose levels were markedly reduced by TGM2 inhibition. Conversely, CD36 receptor and alphavbeta3 integrin levels were not influenced. Of note, lipid accumulation and IL-10 secretion were reduced in macrophages displaying defective efferocytosis. CONCLUSION: Overall, our data define a crucial role of TGM2 activity during macrophage differentiation via mechanisms involving CD14 and SR-AI receptors and show that TGM2 inhibition triggers a pro-inflammatory phenotype. PMID- 27378396 TI - Circulating SIRT1 inversely correlates with epicardial fat thickness in patients with obesity. AB - BACKGROUND AND AIM: Obesity is increasing worldwide and is related to undesirable cardiovascular outcomes. Epicardial fat (EF), the heart visceral fat depot, increases with obesity and correlates with cardiovascular risk. SIRT1, an enzyme regulating metabolic circuits linked with obesity, has a cardioprotective effect and is a predictor of cardiovascular events. We aimed to assess the relationship of EF thickness (EFT) with circulating SIRT1 in patients with obesity. METHODS AND RESULTS: Sixty-two patients affected by obesity and 23 lean controls were studied. Plasma SIRT1 concentration was determined by enzyme-linked immunosorbent assay (ELISA). EFT was measured by echocardiography. Body mass index (BMI), waist circumference, heart rate (HR), blood pressure, and laboratory findings (fasting glucose, insulin, HbA1c, cholesterol, and triglycerides) were assessed. SIRT1 was significantly lower (P = 0.002) and EFT was higher (P < 0.0001) in patients with obesity compared with lean controls. SIRT1 showed a negative correlation with EFT and HR in the obesity group (rho = -0.350, P = 0.005; rho = -0.303, P = 0.008, respectively). After adjustment for obesity-correlated variables, multiple linear regression analysis showed that EFT remained the best correlate of SIRT1 (beta = 0.352, P = 0.016). CONCLUSIONS: Circulating SIRT1 correlates with the visceral fat content of the heart. Serum SIRT1 levels might provide additional information for risk assessment of coronary artery disease in patients with obesity. PMID- 27378397 TI - Current cardiovascular outcomes trials in type 2 diabetes: Perspectives and insight. AB - AIMS: The increased risk of cardiovascular disease in patients with type 2 diabetes has been known for many years. However, until recently the cardiovascular (CV) impact of glucose lowering strategies has been inadequately understood. Major clinical trials have now investigated the impact of intensification of glycemic control upon CV outcomes, as well as the CV effects of glucose management with newer antihyperglycemic agents. DATA SYNTHESIS: Key findings from recently completed CV outcomes trials of dipeptidyl peptidase-4 (DPP4) inhibitors, GLP-1 receptor agonists, and sodium-glucose cotransporter 2 (SGLT2) inhibitors completed thus far are reviewed and summarized. CONCLUSIONS: Multiple trials designed to meet regulatory requirements for CV safety of antihyperglycemic medications have been initiated. The results of several completed CV outcomes trials clarify the risks and benefits associated with newer medications used to manage hyperglycemia in patients with type 2 diabetes, particularly in individuals at high CV risk. Important differences have been noted with respect to heart failure outcomes within the DPP4 inhibitor class, and thus far one agent in the SGLT2 inhibitor class has been found to significantly reduce rates of important CV outcomes. Robust safety related information from trials designed to assess the CV effects of diabetes therapies will permit the incorporation of outcomes-based evidence into the formulation of diabetes care guidelines. PMID- 27378398 TI - DNA brick self-assembly with an off-lattice potential. AB - We report Monte Carlo simulations of a simple off-lattice patchy-particle model for DNA 'bricks'. We relate the parameters that characterise this model with the binding free energy of pairs of single-stranded DNA molecules. We verify that an off-lattice potential parameterised in this way reproduces much of the behaviour seen with a simpler lattice model we introduced previously, although the relaxation of the geometric constraints leads to a more error-prone self-assembly pathway. We investigate the self-assembly process as a function of the strength of the non-specific interactions. We show that our off-lattice model for DNA bricks results in robust self-assembly into a variety of target structures. PMID- 27378399 TI - Standalone ethanol micro-reformer integrated on silicon technology for onboard production of hydrogen-rich gas. AB - A novel design of a silicon-based micro-reformer for onboard hydrogen generation from ethanol is presented in this work. The micro-reactor is fully fabricated with mainstream MEMS technology and consists of an active low-thermal-mass structure suspended by an insulating membrane. The suspended structure includes an embedded resistive metal heater and an array of ca. 20k vertically aligned through-silicon micro-channels per square centimetre. Each micro-channel is 500 MUm in length and 50 MUm in diameter allowing a unique micro-reformer configuration that presents a total surface per projected area of 16 cm(2) cm(-2) and per volume of 320 cm(2) cm(-3). The walls of the micro-channels become the active surface of the micro-reformer when coated with a homogenous thin film of Rh-Pd/CeO2 catalyst. The steam reforming of ethanol under controlled temperature conditions (using the embedded heater) and using the micro-reformer as a standalone device are evaluated. Fuel conversion rates above 94% and hydrogen selectivity values of ca. 70% were obtained when using operation conditions suitable for application in micro-solid oxide fuel cells (micro-SOFCs), i.e. 750 degrees C and fuel flows of 0.02 mlL min(-1) (enough to feed a one watt power source). PMID- 27378400 TI - Eosinophilic dermatosis of haematological malignancy. PMID- 27378401 TI - Reproducibility and validity of a semi-quantitative FFQ for trace elements. AB - The aim of this study was to test the reproducibility and validity of a self administered FFQ for the Trace Element Study of Korean Adults in the Yeungnam area (SELEN). Study subjects were recruited from the SELEN cohort selected from rural and urban areas in Yeungnam, Korea. A semi-quantitative FFQ with 146 items was developed considering the dietary characteristics of cohorts in the study area. In a validation study, seventeen men and forty-eight women aged 38-62 years completed 3-d dietary records (DR) and two FFQ over a 3-month period. The validity was examined with the FFQ and DR, and the reproducibility was estimated using partial correlation coefficients, the Bland-Altman method and cross classification. There were no significant differences between the mean intakes of selected nutrients as estimated from FFQ1, FFQ2 and DR. The median correlation coefficients for all nutrients were 0.47 and 0.56 in the reproducibility and validity tests, respectively. Bland-Altman's index and cross-classification showed acceptable agreement between FFQ1 and FFQ2 and between FFQ2 and DR. Ultimately, 78 % of the subjects were classified into the same and adjacent quartiles for most nutrients. In addition, the weighted kappa value indicated that the two methods agreed fairly. In conclusion, this newly developed FFQ was a suitable dietary assessment method for the SELEN cohort study. PMID- 27378402 TI - Adherence to transfusion strategies in a randomized controlled trial: experiences from the TITRe2 trial. PMID- 27378403 TI - Editorial: Biomedical Engineering Approaches for HIV/AIDS Prophylaxis, Diagnostics and Therapy. PMID- 27378404 TI - Cloning and mineralization-related functions of the calponin gene in Chlamys farreri. AB - Calponin is a widely distributed protein which is associated with the bio mineralization process in vertebrates. Recently, a new type of calponin has been found in shellfish; the present study aimed to determine if this gene in shellfish functions in bio-mineralization, one of the most important processes in a mollusk's growth. We chose Chlamys farreri, a seashell species with great economic value, as the object of the study and obtained its full-length cDNA to study the function of calponin by gene expression analysis, shell notching experiment and RNA interference assays. Calponin in C. farreri is a basic protein that is highly conserved among mollusk species. Except for high expression in the adductor muscle and foot, which correlated with its function of regulating muscle contraction, the calponin gene was expressed more in the mantle than in other tissues. The expression of the gene was induced by shell notching and an RNA interference assay showed that inhibition of calponin expression caused the growth of irregular mineral crystals on the shell. Further analysis indicated that calponin might function by regulating the expression of other mineralization related genes. Calponin is a mineralization-related protein in C. farreri that might influence mineral crystal growth by affecting the expressions of other proteins, such as matrix proteins and mineralization-regulating proteins. PMID- 27378405 TI - Comparison of the effects of human and chicken ghrelin on chicken ovarian hormone release. AB - The aim of the present experiments was to examine the species-specific and cell specific effects of ghrelin on chicken ovarian hormone release. For this purpose, we compared the effects of chicken and human ghrelin on the release of estradiol (E), testosterone (T), progesterone (P) and arginine-vasotocin (AVT) by cultured fragments of chicken ovarian follicles and on the release of T and AVT by cultured ovarian granulosa cells. In cultured chicken ovarian fragments, both human and chicken ghrelin promoted E release. T output was stimulated by chicken ghrelin but not by human ghrelin. No effect of either human or chicken ghrelin on P release was observed. Human ghrelin promoted but chicken ghrelin suppressed AVT release by chicken ovarian fragments. In cultured ovarian granulosa cells, human ghrelin inhibited while chicken ghrelin stimulated T release. Both human and chicken ghrelin suppressed AVT output by chicken granulosa cells. These data confirm the involvement of ghrelin in the control of ovarian secretory activity and demonstrate that the effect of ghrelin is species-specific. The similarity of avian ghrelin on avian ovarian granulosa cells and ovarian fragments (containing both granulosa and theca cells) suggests that ghrelin can influence chicken ovarian hormones primarily by acting on granulosa cells. PMID- 27378406 TI - Cloning and characterization of carboxyl terminus of heat shock cognate 70 interacting protein gene from the silkworm, Bombyx mori. AB - Carboxyl terminus of heat shock cognate 70-interacting protein (CHIP) is an evolutionarily conserved E3 ubiquitin ligase across different eukaryotic species and is known to play a key role in protein quality control. CHIP has two distinct functional domains, an N-terminal tetratricopeptide repeat (TPR) and a C-terminal U-box domain, which are required for the ubiquitination of numerous labile client proteins that are chaperoned by heat shock proteins (HSPs) and heat shock cognate proteins (HSCs). During our screen for CHIP-like proteins in the Bombyx mori databases, we found a novel silkworm gene, Bombyx mori CHIP. Phylogenetic analysis showed that BmCHIP belongs to Lepidopteran lineages. Quantitative reverse transcription-PCR analysis indicated that BmCHIP was relatively highly expressed in the gonad and fat body. A pull-down experiment and auto ubiquitination assay showed that BmCHIP interacted with BmHSC70 and had E3 ligase activity. Additionally, immunohistochemical analysis revealed that BmCHIP was partially co-localized with ubiquitin in BmN4 cells. These data support that BmCHIP plays an important role in the ubiquitin proteasome system as an E3 ubiquitin ligase in B. mori. PMID- 27378407 TI - Molecular cloning and functional characterization of arachidonate 5-lipoxygenase (Alox5), and its expression in response to the ratio of linolenic acid to linoleic acid in diets of large yellow croaker (Larmichthys crocea). AB - This study was conducted to clone and functionally characterize a full-length cDNA encoding arachidonate 5-lipoxygenase (Alox5) from large yellow croaker (Larmichthys crocea) and investigate its gene expression in response to graded dietary ratio of linolenic acid (ALA) to linoleic acid (LNA) (0.03, 0.06, 0.45, 0.90 and 1.51). An isolated 2372bp cDNA clone of Alox5 contained an open reading frame spanning 2025bp encoding a protein with the ability to modify arachidonate acid (AA) to 5-hydroxyeicosatetraenoic (5-HETE). In the liver, the Alox5 mRNA expression levels significantly increased to the maximum when the dietary ALA/LNA increased from 0.03 to 0.06, and then significantly decreased with dietary ALA/LNA increased to 1.51 (P<0.05). In the kidney, the expression levels of Alox5 of fish fed diets with low dietary ALA/LNA (0.03-0.06) were significantly higher than those of fish fed diets with high dietary ALA/LNA (0.45-1.51) (P<0.05). The dual-luciferase reporter assays showed that the nuclear factor kappa B (NF kappaB) could act on cognate cis-acting elements in the promoter of Alox5 and increased the transcription of Alox5. Results of the present study suggested that the expression of Alox5 is higher in croakers fed high concentrations of LNA compared to those fed high concentrations of ALA, which might be regulated by NF kappaB and contribute to the inflammation process by catalyzing the dioxygenation of AA. PMID- 27378408 TI - First report of spotted fever group Rickettsia in Cuba. PMID- 27378409 TI - Crimean-Congo hemorrhagic fever virus lineages Europe 1 and Europe 2 in Bulgarian ticks. AB - Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne human viral disease with fatality rate up to 30%. Two genetic lineages of CCHF virus (CCHFV) are present in Europe - lineage Europe 1 which contains pathogenic CCHFV strains, and lineage Europe 2 consisting of AP92 and AP92-like strains. In order to investigate CCHFV distribution and potential risk for humans, ticks were collected from livestock in the five districts where CCHF cases have been reported in the last five years in Bulgaria. CCHFV lineage Europe 1 was detected in 39 of 623 Hyalomma marginatum ticks (6.3%; range per village 2.7-15.2%), while CCHFV lineage Europe 2 was detected for the first time in Bulgaria in 49 of 415 Rhipicephalus sanguineus sensu lato ticks (11.8%; range 0-58.3%). The present study shows that both Europe 1 and Europe 2 CCHFV lineages are present in Bulgaria. The pathogenic role of the AP92-like strains remains to be elucidated. PMID- 27378410 TI - Open arms, conflicted hearts: nurse-practitioner's attitudes towards working with lesbian, gay and bisexual patients. AB - AIMS AND OBJECTIVES: To explore nurse-practitioner's attitudes towards working with lesbian, gay and bisexual patients. BACKGROUND: Literature suggests that lesbians, gay men and bisexuals have significant health disparities compared to heterosexuals. Although the reasons are multifactorial, research suggests that attitudes of healthcare providers (HCPs) may be a contributing factor in both accessing and receiving care. There is currently no literature exploring the attitudes of the approximately 300,000 nurse-practitioners in the United States. Thus, nurse-practitioners strengths and challenges in providing care to sexual minorities are unknown. DESIGN: As part of a larger study, Corbin & Strauss' grounded theory methodology was used to explore the attitudes towards lesbian, gay and bisexual patients among primary care nurse-practitioners in NYC. METHODS: Data were collected via individual semi-structured interviews with nurse practitioners currently in practice in primary or outpatient care in NYC (n = 19). Data were evaluated using the three-step constant comparison method. RESULTS: Nurse-practitioners in this study had varied, often overlapping and sometimes conflicting, attitudes about working with lesbian, gay and bisexual patients. The main theme identified was 'open arms, conflicted hearts' with three major subthemes - feeling at home, struggling to maintain professionalism and finding comfort under the umbrella of diversity. CONCLUSIONS: Nurse-practitioner participants in this study had varied attitudes about working with lesbian, gay and bisexual patients, ranging from open, confident and comfortable to ambivalent, cautious and unsure about working with lesbian, gay and bisexual patients generally and specifically regarding the health needs of this population. RELEVANCE TO CLINICAL PRACTICE: This study highlights the inadequate didactic and clinical preparation most nurse-practitioners feel they have to care for lesbian, gay and bisexual patients. There is a need for increased education for registered nurses and nurse-practitioners regarding lesbian, gay and bisexual culture, their unique healthcare needs, as well as the role of stigma and marginalisation in caring for vulnerable populations. PMID- 27378411 TI - Impact of Mental Disorders on the Association Between Adherence to Antihypertensive Agents and All-Cause Healthcare Costs. AB - Depression and anxiety are factors associated with poor adherence to medications that lead to increased healthcare costs. The authors hypothesize that these conditions will moderate the association between adherence and healthcare costs. The aim was to examine the healthcare costs associated with adherence to antihypertensive agents in the elderly with and without depression and anxiety. The sample included participants with hypertension and used hypertensive agents (N=926). Medication possession ratio was used to calculate medication adherence. Mean total healthcare costs included costs for inpatient stays, emergency department visits, outpatient visits, physician fees, and outpatient medications. Mental disorders were assessed using a questionnaire based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. The total healthcare costs were significantly greater for nonadherent participants with depression/anxiety than for adherent participants without depression/anxiety (Delta$1841, P<.0001). This study suggests that treating mental disorders in elderly patients with hypertension will decrease total healthcare costs. PMID- 27378414 TI - Structural varieties of selectively mixed G- and C-rich short DNA sequences studied with electrospray ionization mass spectrometry. AB - Short guanine(G)-repeat and cytosine(C)-repeat DNA strands can self-assemble to form four-stranded G-quadruplexes and i-motifs, respectively. Herein, G-rich and C-rich strands with non-G or non-C terminal bases and different lengths of G- or C-repeats are mixed selectively in pH 4.5 and 6.7 ammonium acetate buffer solutions and studied by electrospray ionization mass spectrometry (ESI-MS). Various strand associations corresponding to bi-, tri- and tetramolecular ions are observed in mass spectra, indicating that the formation of quadruplex structures is a random strand by strand association process. However, with increasing incubation time for the mixtures, initially associated hybrid tetramers will transform into self-assembled conformations, which is mainly driven by the structural stability. The melting temperature values of self assembled quadruplexes suggest that the length of G-repeats or C-repeats shows more significant effect on the stability of quadruplex structures than that of terminal residues. Accordingly, we can obtain the self-associated tetrameric species generated from the mixtures of various homologous G- or C-strands efficiently by altering the length of G- or C-repeats. Our studies demonstrate that ESI-MS is a very direct, fast and sensitive tool to provide significant information on DNA strand associations and stoichiometric transitions, particularly for complex mixtures. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27378415 TI - Full-genome based molecular characterization of encephalitis-associated bovine astroviruses. AB - Novel types of astrovirus have been identified recently in association with neurological disease in cattle. Among those viruses is bovine astrovirus CH13 (BoAstV CH13) that has been identified in Switzerland in a cow with encephalitis. Molecular testing by a combination of reverse transcription (RT-) PCR and in situ hybridization (ISH) indicated that astrovirus infection accounts for around one quarter of viral encephalitis cases of unknown etiology in cattle. Yet, it remained to be explored whether these animals were infected by BoAstV CH13 or other astrovirus species. In the present study we sequenced the entire astrovirus genome in brain tissues of eight RT-PCR and/or ISH positive cattle. Phylogenetic comparison of the genomic RNA and the encoded non-structural and structural proteins revealed that all these astrovirus strains were very similar to BoAstV CH13 as well as to a bovine encephalitis strain reported from the USA (BoAstV NeuroS1), and clearly distinct from other previously reported astroviruses. Conserved 5' and 3' untranslated regions (UTRs) were predicted to display distinct secondary RNA structures, which likely play a role in viral RNA replication and/or protein translation. Based on these data we propose that BoAstV CH13/NeuroS1 represents a new genotype species within the genus Mammastrovirus. The high degree of similarity between the strains and their relative distance to other genotype species suggest that during evolution some astroviruses acquired factors that specifically contribute to neuroinvasion. PMID- 27378416 TI - Genetic parameters for thermoregulation and production traits in lactating sows reared in tropical climate. AB - The objective of this study was to estimate the genetic parameters for thermoregulation traits and the relationships with performance of Large White lactating sows reared in a tropical humid climate. The thermoregulation traits were rectal temperature (RT), cutaneous temperature (CT) and respiratory rate (RR) during lactation measured in the afternoon (1200 h) and in the morning (0700 h). The production traits were sow's average daily feed intake (ADFI), litter BW gain (LBWg) and sow's proportion of BW change between farrowing and weaning (BWc). Complete data included 931 lactating performance on 329 Large White sows from the INRA experimental unit in Guadeloupe (French West Indies). Random regression models using linear spline functions were used for longitudinal data (RT, CT, RR and daily feed intake). Results showed that when ignoring values at the beginning and the end of lactation, the traits studied can be treated as the same trait throughout days of lactation, with fairly constant heritability and variance. However, largest heritabilities and genetic variances were estimated in mid-lactation. Heritability estimates on average performance during lactation were low to moderate for thermoregulation traits (0.35+/-0.09 for RT, 0.34+/-0.12 for CT and 0.39+/-0.13 for RR). Heritability estimates for production traits were 0.26+/-0.08 for ADFI, 0.20+/-0.07 for BWc and 0.31+/-0.09 for LBWg. Significant genetic correlations between thermoregulation traits and production traits were only obtained for ADFI and RR (0.35+/-0.12). From this study it can be concluded that thermoregulation traits are heritable, indicating that there are genetic differences in heat stress tolerance in lactating Large White sows. PMID- 27378418 TI - Evidence for social cooperation in rodents by automated maze. AB - Social cooperation is defined as a joint action for mutual benefit that depends on the individual and the counterparts' behaviors. To gain valid evidence for social cooperation behavior we conducted a series of experiments in our suggested fully automated non-conditioned maze and depicted three major findings: (i) During 18 days of training the rats showed a progressive social learning curve as well as latent social learning; (ii) Examining the perceptual communication between the cooperating partners, we found a correlation between the available perceptual modalities and the social cooperation performance; and (iii) Investigating contextual learning as a competing process to the social cooperation, we found that additional contextual cues impaired the social cooperation performance. In conclusion, our suggested automated cooperation maze is designed to further our understanding of social cooperation under normal conditions, such as decision-making, and to examine the neural basis of social cooperation. A variety of neuropsychiatric disorders are characterized by disruptions in social behavior and social cognition, including depression, autism spectrum disorders, obsessive-compulsive disorder, and schizophrenia. Thus, on the pathological end, our maze for social cooperation evaluation can contribute significantly to the investigation of a wide range of social cooperation impairments in a rodent model. PMID- 27378417 TI - Multivariate Neural Representations of Value during Reward Anticipation and Consummation in the Human Orbitofrontal Cortex. AB - The role of the orbitofrontal cortex (OFC) in value processing is a focus of research. Conventional imaging analysis, where smoothing and averaging are employed, may not be sufficiently sensitive in studying the OFC, which has heterogeneous anatomical structures and functions. In this study, we employed representational similarity analysis (RSA) to reveal the multi-voxel fMRI patterns in the OFC associated with value processing during the anticipatory and the consummatory phases. We found that multi-voxel activation patterns in the OFC encoded magnitude and partial valence information (win vs. loss) but not outcome (favourable vs. unfavourable) during reward consummation. Furthermore, the lateral OFC rather than the medial OFC encoded loss information. Also, we found that OFC encoded values in a similar way to the ventral striatum (VS) or the anterior insula (AI) during reward anticipation regardless of motivated response and to the medial prefrontal cortex (MPFC) and the VS in reward consummation. In contrast, univariate analysis did not show changes of activation in the OFC. These findings suggest an important role of the OFC in value processing during reward anticipation and consummation. PMID- 27378419 TI - Dual-Cross-Linked Methacrylated Alginate Sub-Microspheres for Intracellular Chemotherapeutic Delivery. AB - Intracellular delivery vehicles comprised of methacrylated alginate (Alg-MA) were developed for the internalization and release of doxorubicin hydrochloride (DOX). Alg-MA was synthesized via an anhydrous reaction, and a mixture of Alg-MA and DOX was formed into sub-microspheres using a water/oil emulsion. Covalently cross linked sub-microspheres were formed via exposure to green light, in order to investigate effects of cross-linking on drug release and cell internalization, compared to traditional techniques, such as ultraviolet (UV) light irradiation. Cross-linking was performed using light exposure alone or in combination with ionic cross-linking using calcium chloride (CaCl2). Alg-MA sub-microsphere diameters were between 88 and 617 nm, and zeta-potentials were between -20 and 37 mV. Using human lung epithelial carcinoma cells (A549) as a model, cellular internalization was confirmed using flow cytometry; different sub-microsphere formulations varied the efficiency of internalization, with UV-cross-linked sub microspheres achieving the highest internalization percentages. While blank (nonloaded) Alg-MA submicrospheres were noncytotoxic to A549 cells, DOX-loaded sub-microspheres significantly reduced mitochondrial activity after 5 days of culture. Photo-cross-linked Alg-MA sub-microspheres may be a potential chemotherapeutic delivery system for cancer treatment. PMID- 27378421 TI - An observational study on the incidence of tuberculosis among a cohort of HIV infected adults in a setting with low prevalence of tuberculosis. AB - BACKGROUND: Tuberculosis (TB) remains a main cause of morbidity and mortality among individuals infected with HIV. We investigated the incidence of TB among a cohort of HIV infected patients attending a setting with low TB burden where screening for latent TB infection is not routinely carried out. METHODS: an observational cohort study on HIV-infected adults attending the HIV clinic at Queen Elizabeth Hospital Birmingham, UK between 1 January 2011 and 30 September 2015. Patients with culture-proven TB after HIV diagnosis, or those treated for clinical diagnosis of the infection, were classified as having "active TB". RESULTS: 1824 patients were included in the study (5347 patient years of follow up), of whom 21 patients developed TB (16 microbiology confirmed). Of the 666 new HIV diagnoses, six patients developed TB within one month, giving a TB prevalence at the time of HIV diagnosis of 0.9%. The total TB incidence for the remaining 1818 patients was 2.81 cases per 1000 patient years (95% CI: 1.63-4.53). TB incidence was significantly more common among patients with CD4 <= 200 cells/mm3 compared to those with CD4 > 500 cells/mm3 (28.2 vs. 1.22 per 1000 patient years, p < 0.001), and in patients with VL >= 40 copies/mL compared to <40 copies/mL (8.30 vs. 1.42, p < 0.001). CONCLUSION: In settings with low TB prevalence, early start of combined antiretroviral therapy and intensified TB case finding protocols may significantly reduce the incidence of TB. PMID- 27378420 TI - Optimizing rice plant photosynthate allocation reduces N2O emissions from paddy fields. AB - Rice paddies are a major source of anthropogenic nitrous oxide (N2O) emissions, especially under alternate wetting-drying irrigation and high N input. Increasing photosynthate allocation to the grain in rice (Oryza sativa L.) has been identified as an effective strategy of genetic and agronomic innovation for yield enhancement; however, its impacts on N2O emissions are still unknown. We conducted three independent but complementary experiments (variety, mutant study, and spikelet clipping) to examine the impacts of rice plant photosynthate allocation on paddy N2O emissions. The three experiments showed that N2O fluxes were significantly and negatively correlated with the ratio of grain yield to total aboveground biomass, known as the harvest index (HI) in agronomy (P < 0.01). Biomass accumulation and N uptake after anthesis were significantly and positively correlated with HI (P < 0.05). Reducing photosynthate allocation to the grain by spikelet clipping significantly increased white root biomass and soil dissolved organic C and reduced plant N uptake, resulting in high soil denitrification potential (P < 0.05). Our findings demonstrate that optimizing photosynthate allocation to the grain can reduce paddy N2O emissions through decreasing belowground C input and increasing plant N uptake, suggesting the potential for genetic and agronomic efforts to produce more rice with less N2O emissions. PMID- 27378422 TI - Sirtuin1 promotes osteogenic differentiation through downregulation of peroxisome proliferator-activated receptor gamma in MC3T3-E1 cells. AB - Osteoporosis is a skeletal disorder characterized by bone loss, resulting in architectural deterioration of the skeleton, decreased bone strength and an increased risk of fragility fractures. Strengthening osteogenesis is an effective way to relieve osteoporosis. Sirtuin1 (Sirt1) is a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, which is reported to be involved in improving osteogenesis. Sirt1 targets peroxisome proliferator-activated receptor gamma (PPARgamma) in the regulation of adipose tissues; however, the molecular mechanism of Sirt1 in osteogenic differentiation is still unknown. PPARgamma tends to induce more adipogenic differentiation rather than osteogenic differentiation. Hence, we hypothesized that Sirt1 facilitates osteogenic differentiation through downregulation of PPARgamma signaling. Mouse pre osteoblastic MC3T3-E1 cells were cultured under osteogenic medium. Sirt1 was overexpressed through plasmid transfection. The results showed that high expression of Sirt1 was associated with increased osteogenic differentiation, as indicated by quantitative PCR and Western blot analysis of osteogenic markers, and Von Kossa staining. Sirt1 overexpression also directly and negatively regulated the expression of PPARgamma and its downstream molecules. Use of the PPARgamma agonist Rosiglitazone, reversed the effects of Sirt1 on osteogenic differentiation. Using constructed luciferase plasmids, we demonstrated a role of Sirt1 in inhibiting PPARgamma-induced activity and expression of adipocyte specific genes, including acetyl-coenzyme A carboxylase (Acc) and fatty acid binding protein 4 (Fabp4). The interaction between Sirt1 and PPARgamma was further confirmed using co-immunoprecipitation analysis. Together, these results reveal a novel mechanism for Sirt1 in osteogenic differentiation through downregulation of PPARgamma activity. These findings suggest that the Sirt1 PPARgamma pathway may represent a potential target for enhancement of osteogenesis and treatment of osteoporosis. PMID- 27378423 TI - Ghrelin inhibits high glucose-induced 16HBE cells apoptosis by regulating Wnt/beta-catenin pathway. AB - Ghrelin has a protective effect on diabetes and its complications. To expound its probable molecular mechanisms, we investigated the effects of ghrelin on high glucose (HG)-induced cell apoptosis and intracellular signaling pathways in cultured human bronchial epithelial cells (16HBE). In this study, we firstly came to conclusion that HG-induced 16HBE apoptosis was significantly inhibited by co treatment of ghrelin. The molecular mechanism of ghrelin-induced protective effects for lungs is still not understood. We reported here for the first time that ghrelin can not only eliminate apoptosis of 16HBE, but also regulate the disordered cell cycle caused by HG. We speculated here that ghrelin inhibits the apoptosis of 16HBE by regulating the abnormal cell cycle to some extent. The mechanism may be that ghrelin up-regulates the expression of cyclin D1 via regulating Wnt/beta-catenin pathway, which has an intimate relationship with lung diseases. These results suggested the possible role of ghrelin in treating diabetic lung diseases, especially in view of its low toxicity in humans. PMID- 27378424 TI - Open reading frames 1a and 1b of the porcine reproductive and respiratory syndrome virus (PRRSV) collaboratively initiate viral minus-strand RNA synthesis. AB - The porcine reproductive and respiratory syndrome virus (PRRSV) causes a persistent threat to the swine industry, especially when highly pathogenic PRRSV (HP-PRRSV) emerges. Previous studies have indicated that PRRSV RNA synthesis was correlated with HP-PRRSV virulence. PRRSV RNA synthesis includes genomic RNA and sub-genomic mRNA, and these processes require minus-strand RNA as a template. However, the mechanisms involved in PRRSV minus-strand RNA synthesis are not fully understood. A mini-genome system can be used to assess viral replication mechanisms and to evaluate the effects of potential antiviral drugs on viral replicase activities. In this study, we developed a mini-genome system that uses firefly luciferase as a reporter. Based on this system, we found that PRRSV RNA dependent RNA polymerase nsp9 alone failed to activate virus minus-strand RNA synthesis. We also demonstrated that combinations of open reading frames 1a (ORF1a) and ORF1b are necessary for viral minus-strand RNA synthesis. PMID- 27378425 TI - Myricetin is a novel inhibitor of human inosine 5'-monophosphate dehydrogenase with anti-leukemia activity. AB - Human inosine 5'-monophosphate dehydrogenase (hIMPDH) is a rate-limiting enzyme in the de novo biosynthetic pathway of purine nucleotides, playing crucial roles in cellular proliferation, differentiation, and transformation. Dysregulation of hIMPDH expression and activity have been found in a variety of human cancers including leukemia. In this study, we found that myricetin, a naturally occurring phytochemical existed in berries, wine and tea, was a novel inhibitor of human type 1 and type 2 IMPDH (hIMPDH1/2) with IC50 values of 6.98 +/- 0.22 MUM and 4.10 +/- 0.14 MUM, respectively. Enzyme kinetic analysis using Lineweaver-Burk plot revealed that myricetin is a mix-type inhibitor for hIMPDH1/2. Differential scanning fluorimetry and molecular docking simulation data demonstrate that myricetin is capable of binding with hIMPDH1/2. Myricetin treatment exerts potent anti-proliferative and pro-apoptotic effects on K562 human leukemia cells in a dose-dependent manner. Importantly, cytotoxicity of myricetin on K562 cells were markedly attenuated by exogenous addition of guanosine, a salvage pathway of maintaining intracellular pool of guanine nucleotides. Taking together, these results indicate that natural product myricetin exhibits potent anti-leukemia activity by interfering with purine nucleotides biosynthetic pathway through the suppression of hIMPDH1/2 catalytic activity. PMID- 27378426 TI - Cardioprotection by 6-gingerol in diabetic rats. AB - The current study was conducted to evaluate the effect of 6-gingerol (6G) on cardiac complications in streptozotocin (STZ)-induced diabetic (DM) rats. STZ induced DM rats (single 50 mg/kg i.p. injection, 15 days prior to drug treatment) or time-matched controls were treated with 6G (75 mg/day route orally). After a further 8 weeks, blood was collected for biochemical analysis and 8-isoprostenol was measured in urine. Cardiac hemodynamics and ECG was assessed. 6G significantly attenuated the increased level of blood glucose in diabetic rats and improved cardiac hemodynamics in including RR interval, max dP/dt, min dP/dt and Tau. In addition, 6G alleviated the elevated ST segment, T amplitude and R amplitude with no significant effect on disturbed levels of adiponectin, TGF-beta or 8-isoprostenol induced by diabetes. The results showed that treatment with 6G has an ameliorative effect on cardiac dysfunction induced by diabetes. Which may be not related to its potential antioxidant effect. PMID- 27378427 TI - Sinomenine alleviates high glucose-induced renal glomerular endothelial hyperpermeability by inhibiting the activation of RhoA/ROCK signaling pathway. AB - As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression in HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders. PMID- 27378428 TI - MLF1IP is correlated with progression and prognosis in luminal breast cancer. AB - Myeloid leukemia factor 1-interacting protein (MLF1IP) has been found to be involved in the progression of several malignancies. The potential correlation between MLF1IP and clinical outcome in patients with luminal breast cancer, however, remains unknown. In the present study, we demonstrated that MLF1IP was significantly upregulated in luminal breast cancer tissue compared with adjacent normal tissue both in validated cohort and TCGA cohort. Upregulated expression of MLF1IP was correlated with more often lymph node metastasis and negative progesterone receptor expression in TCGA cohorts. Kaplan-Meier analysis indicated that patients with high MLF1IP expression had significantly lower overall survival. Moreover, multivariate analysis revealed that high MLF1IP expression was independent high risk factor as well as old age (>60) and distant metastasis. This study provides new insights and evidences that MLF1IP over-expression plays important roles in progression of luminal breast cancer. However, the precise cellular mechanisms for MLF1IP in luminal breast cancer need to be further explored. PMID- 27378429 TI - A Porous Cu(II)-MOF with Proline Embellished Cavity: Cooperative Catalysis for the Baylis-Hillman Reaction. AB - l-Proline has been covalently attached in a rigid linear ligand, H4L, having an isophthalate moiety at each terminal to form the chiral ligand, H4LPRO. This linker has been used for the construction of a porous MOF, LCuPRO. The free l proline moiety in the cavity of the framework in the presence of imidazole as a cocatalyst functions synergistically to catalyze the Baylis-Hillman reaction between alpha,beta-unsaturated carbonyl compounds and aromatic aldehydes. High porosity of the framework is proven by the nitrogen adsorption isotherm. PMID- 27378430 TI - Establishment of replacement International Standard 13/132 for human antibodies to Toxoplasma gondii. AB - Sixteen laboratories carried out a collaborative study to validate 13/132 as a replacement International Standard (IS) for TOXM (3rd IS for anti-Toxoplasma Serum, Human, 1000 IU). 13/132 is a freeze dried preparation of pooled human plasma from six donors who experienced a recent Toxoplasma gondii infection. The potency of 13/132 was compared to TOXM and 01/600 (1st IS for anti-Toxoplasma IgG, Human, 20 IU). Samples were tested for IgA, IgG, IgG avidity and IgM in agglutination assays; enzyme linked immunosorbent assays (ELISA), enzyme linked fluorescent assays, immunoblots, immunofluorescence assays and the Sabin-Feldman dye test for Ig. 13/132 was strongly positive for Ig, IgA, IgG and IgM and the reproducibility was very good. 13/132 contains high levels of anti-Toxoplasma Ig, IgG and IgM and its potency falls between TOXM and 01/600. The avidity of IgG was found to be low, similar to the avidity of IgG from TOXM. 13/132 was established by the Expert Committee on Biological Standardization as the 4th IS for Antibodies, Human, to T. gondii with an assigned unitage of 160 IU per ampoule for Ig by dye test and 263 U per ampoule for IgG by ELISA. PMID- 27378431 TI - Numerical modelling strategies for the urban atmosphere: general discussion. PMID- 27378432 TI - Transcutaneous electrical stimulation (TES) for treatment of constipation in children. AB - BACKGROUND: Childhood constipation is a common problem with substantial health, economic and emotional burdens. Existing therapeutic options, mainly pharmacological, are not consistently effective, and some are associated with adverse effects after prolonged use. Transcutaneous electrical stimulation (TES), a non-pharmacological approach, is postulated to facilitate bowel movement by modulating the nerves of the large bowel via the application of electrical current transmitted through the abdominal wall. OBJECTIVES: Our main objective was to evaluate the effectiveness and safety of TES when employed to improve bowel function and constipation-related symptoms in children with constipation. SEARCH METHODS: We searched MEDLINE (PubMed) (1950 to July 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2015), EMBASE (1980 to July 2015), the Cochrane IBD Group Specialized Register, trial registries and conference proceedings to identify applicable studies . SELECTION CRITERIA: Randomized controlled trials that assessed any type of TES, administered at home or in a clinical setting, compared to no treatment, a sham TES, other forms of nerve stimulation or any other pharmaceutical or non pharmaceutical measures used to treat constipation in children were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion, extracted data and assessed risk of bias of the included studies. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for categorical outcomes data and the mean difference (MD) and corresponding 95% CI for continuous outcomes. MAIN RESULTS: One study from Australia including 46 children aged 8 to 18 years was eligible for inclusion. There were multiple reports identified, including one unpublished report, that focused on different outcomes of the same study. The study had unclear risk of selection bias, high risks of performance, detection and attrition biases, and low risks of reporting biases.There were no significant differences between TES and the sham control group for the following outcomes: i).number of children with > 3 complete spontaneous bowel movements (CSBM) per week (RR 1.07, 95% CI 0.74 to 1.53, one study, 42 participants) ( QUALITY OF EVIDENCE: very low, due to high risk of bias and serious imprecision ), ii). number of children with improved colonic transit assessed radiologically (RR 5.00, 95% CI 0.79 to 31.63; one study, 21 participants) ( QUALITY OF EVIDENCE: very low, due to high risk of bias, serious imprecision and indirectness of the outcome). However, mean colonic transit rate, measured as the position of the geometric centre of the radioactive substance ingested along the intestinal tract, was significantly higher in children who received TES compared to sham (MD 1.05, 95% CI 0.36 to 1.74; one study, 30 participants) ( QUALITY OF EVIDENCE: very low, due to high risk of bias , serious imprecision and indirectness of the outcome). There was no significant difference between the two groups in the number of children with improved soiling related symptoms (RR 2.08, 95% CI 0.86 to 5.00; one study, 25 participants) ( QUALITY OF EVIDENCE: very low, due to high risk of bias and serious imprecision). There was no significant difference in the number of children with improved quality of life (QoL) (RR 4.00, 95% CI 0.56 to 28.40; one study, 16 participants) ( QUALITY OF EVIDENCE: very low, due to high risk of bias issues and serious imprecision ). There were also no significant differences in in self-perceived (MD 5.00, 95% CI -1.21 to 11.21) or parent-perceived QoL (MD -0.20, 95% CI -7.57 to 7.17, one study, 33 participants for both outcomes) (QUALITY OF EVIDENCE for both outcomes: very low, due to high risk of bias and serious imprecision). No adverse effects were reported in the included study. AUTHORS' CONCLUSIONS: The very low quality evidence gathered in this review does not suggest that TES provides a benefit for children with chronic constipation. Further randomized controlled trials assessing TES for the management of childhood constipation should be conducted. Future trials should include clear documentation of methodologies, especially measures to evaluate the effectiveness of blinding, and incorporate patient-important outcomes such as the number of patients with improved CSBM, improved clinical symptoms and quality of life. PMID- 27378433 TI - A lipidomics study reveals hepatic lipid signatures associating with deficiency of the LDL receptor in a rat model. AB - The low-density lipoprotein receptor (LDLR) plays a critical role in the liver for the clearance of plasma low-density lipoprotein (LDL). Its deficiency causes hypercholesterolemia in many models. To facilitate the usage of rats as animal models for the discovery of cholesterol-lowering drugs, we took a genetic approach to delete the LDLR in rats aiming to increase plasma LDL cholesterol (LDL-C). An LDLR knockout rat was generated via zinc-finger nuclease technology, which harbors a 19-basepair deletion in the seventh exon of the ldlr gene. As expected, deletion of the LDLR elevated total cholesterol and total triglyceride in the plasma, and caused a tenfold increase of plasma LDL-C and a fourfold increase of plasma very low-density lipoprotein (VLDL-C). A lipidomics analysis revealed that deletion of the LDLR affected hepatic lipid metabolism, particularly lysophosphatidylcholines, free fatty acids and sphingolipids in the liver. Cholesterol ester (CE) 20:4 also displayed a significant increase in the LDLR knockout rats. Taken together, the LDLR knockout rat offers a new model of hypercholesterolemia, and the lipidomics analysis reveals hepatic lipid signatures associating with deficiency of the LDL receptor. PMID- 27378434 TI - PFA fixation enables artifact-free super-resolution imaging of the actin cytoskeleton and associated proteins. AB - Super-resolution microscopy (SRM) allows precise localization of proteins in cellular organelles and structures, including the actin cytoskeleton. Yet sample preparation protocols for SRM are rather anecdotal and still being optimized. Thus, SRM-based imaging of the actin cytoskeleton and associated proteins often remains challenging and poorly reproducible. Here, we show that proper paraformaldehyde (PFA)-based sample preparation preserves the architecture of the actin cytoskeleton almost as faithfully as gold-standard glutaraldehyde fixation. We show that this fixation is essential for proper immuno-based localization of actin-binding and actin-regulatory proteins involved in the formation of lamellipodia and ruffles, such as mDia1, WAVE2 and clathrin heavy chain, and provide detailed guidelines for the execution of our method. In summary, proper PFA-based sample preparation increases the multi-color possibilities and the reproducibility of SRM of the actin cytoskeleton and its associated proteins. PMID- 27378435 TI - Quality comparison of elephant apple juices after high-pressure processing and thermal treatment. AB - BACKGROUND: In the present work, the effect of high pressure processing (HPP) on the quality parameters (pH, degrees Brix, total acidity, viscosity, colour, antioxidant activity, total phenols, total flavonoids, microbial flora, and sensory analysis) of elephant apple (Dillenia indica) juice was investigated. The juice samples were analysed periodically (0, 1, 2, 5, 10, 20, 30, 40, 50 and 60 days) during 60 days of storage period and results were compared with thermally processed as well as with untreated (fresh juice) samples. RESULTS: Slight variations had been observed in the quality parameters like pH, degrees Brix and total acidity. Other parameters like colour values, antioxidant activity, total phenols and total flavonoids were varied significantly (P < 0.05) in between the treated (HPP and thermal) and untreated juice samples. The microbial counts of the HPP treated samples were lower than the other samples. Sensory results also showed similar results to those of the other analyses that the treated samples were better for consumption rather than the untreated samples. The shelf-life of the HPP processed elephant apple juice was established as 60 days at 4 degrees C. CONCLUSION: This study showed that application of HPP effectively maintained quality attributes and extended shelf life of the elephant apple juice. It may be suggested that application of HPP could be considered for commercial application during storage and marketing. (c) 2016 Society of Chemical Industry. PMID- 27378436 TI - Diagnostic reference levels of paediatric computed tomography examinations performed at a dedicated Australian paediatric hospital. AB - INTRODUCTION: Diagnostic Reference Levels (DRL) of procedures involving ionizing radiation are important tools to optimizing radiation doses delivered to patients and in identifying cases where the levels of doses are unusually high. This is particularly important for paediatric patients undergoing computed tomography (CT) examinations as these examinations are associated with relatively high-dose. METHODS: Paediatric CT studies, performed at our institution from January 2010 to March 2014, have been retrospectively analysed to determine the 75th and 95th percentiles of both the volume computed tomography dose index (CTDIvol ) and dose length product (DLP) for the most commonly performed studies to: establish local diagnostic reference levels for paediatric computed tomography examinations performed at our institution, benchmark our DRL with national and international published paediatric values, and determine the compliance of CT radiographer with established protocols. RESULTS: The derived local 75th percentile DRL have been found to be acceptable when compared with those published by the Australian National Radiation Dose Register and two national children's hospitals, and at the international level with the National Reference Doses for the UK. The 95th percentiles of CTDIvol for the various CT examinations have been found to be acceptable values for the CT scanner Dose-Check Notification. Benchmarking CT radiographers shows that they follow the set protocols for the various examinations without significant variations in the machine setting factors. CONCLUSION: The derivation of DRL has given us the tool to evaluate and improve the performance of our CT service by improved compliance and a reduction in radiation dose to our paediatric patients. We have also been able to benchmark our performance with similar national and international institutions. PMID- 27378437 TI - Constant supervision of bathing in French public swimming pools: an unrealistic regulatory requirement? AB - In France, to prevent drowning accidents in public swimming pools (PSPs), bathing must be constantly supervised by qualified staff. However, fatal drowning regularly occurs in supervised aquatic facilities. A review of the literature shows that human supervision is a complex task. The aim of this research is to fully assess the periods during which supervision is not carried out, or carried out in an inadequate manner. The observations made in 108 French PSPs show that supervision is not carried out 18% of the time and that it is carried out inadequately 33% of the time. The medical literature shows that, in order to expect to survive without after-effects, an immersed victim requires intervention within a time limit of not more than three minutes; however, we noted, over a total observation time of 54 hours, 147 periods (29.8%) during which the supervision system was degraded for three minutes or more. This quantification research on the periods of degraded supervision is complemented by an identification of the causes leading to these degradations, from which we can draw interesting areas for improvement, particularly from an organizational point of view, in order to improve safety management in French PSPs. PMID- 27378438 TI - Much Higher Case-fatality Rates of Index Cases. Commentary: Differences in the Epidemiology of Human Cases of Avian Influenza A(H7N9) and A(H5N1) Viruses Infection. PMID- 27378440 TI - Oscillatory power and functional connectivity in the speech change detection network. AB - We used passive and active oddball conditions with two types of acoustic contrasts, between speech syllables that cross phonetic boundaries (across category, AC) and between those that do not cross them (within-category, WC), to explore the effects of meaningful speech contrasts on the dynamics of the neural network underlying the mismatch negativity (MMN) to the speech deviants. We found that easily detected AC deviants evoked a MMN response that lateralized to the left hemisphere, but the very difficult to detect WC deviants did not elicit a MMN response at all. Based on independent component analysis of the continuous EEG, we computed both power changes within, and functional connectivity (phase synchronization) between, brain regional sources comprising the neural network associated with the MMN for these speech stimuli. We found that for acoustic contrasts for which an MMN was generated, power changes suggested whether a particular brain region was more involved with processing standards or deviants. Moreover, we not only replicated the changes in functional connectivity between orbitofrontal cortex and superior temporal gyrus found in previous experiments, but also found significant increases in synchronization between those regions and regions of the left inferior frontal gyrus (Broca's area), which is thought to be involved in the storage and retrieval of phonological and semantic information. PMID- 27378439 TI - The effects of ongoing distraction on the neural processes underlying signal detection. AB - Distraction can impede our ability to detect and effectively process task relevant stimuli in our environment. Here we leveraged the high temporal resolution of event-related potentials (ERPs) to study the neural consequences of a global, continuous distractor on signal-detection processes. Healthy, young adults performed the dSAT task, a translational sustained-attention task that has been used across different species and in clinical groups, in the presence and absence of ongoing distracting stimulation. We found the presence of distracting stimuli impaired participants' ability to behaviorally detect task-relevant signal stimuli and greatly affected the neural cascade of processes underlying signal detection. Specifically, we found distraction reduced an anterior and a posterior early-latency N2 ERP component (~140-220ms) and modulated long-latency, detection-related P3 components (P3a: ~200-330ms, P3b: 300-700ms), even to correctly detected targets. These data provide evidence that distraction can induce powerful alterations in the neural processes related to signal detection, even when stimuli are behaviorally detected. PMID- 27378441 TI - Impaired assessment of cumulative lifetime familiarity for object concepts after left anterior temporal-lobe resection that includes perirhinal cortex but spares the hippocampus. AB - The ability to recognize the prior occurrence of objects can operate effectively even in the absence of successful recollection of episodic contextual detail about a relevant past object encounter. The pertinent process, familiarity assessment, is typically probed in humans with recognition-memory tasks that include an experimentally controlled study phase for a list of items. When meaningful stimuli such as words or pictures of common objects are employed, participants must judge familiarity with reference to the recent experimental encounter rather than their lifetime of autobiographical experience, which may have involved hundreds or thousands of exposures across numerous episodic contexts. Humans can, however, also judge the cumulative familiarity of objects concepts they have encountered over their lifetime. At present, little is known about the cognitive and neural mechanisms that support this ability. Here, we tested an individual (NB) with a rare left anterior temporal-lobe lesion that included perirhinal cortex but spared the hippocampus, who had previously been found to exhibit selective impairments in familiarity assessment on verbal recognition-memory tasks. As NB exhibits normal recollection abilities, her case presents a unique opportunity to examine potential links between both types of familiarity. In Experiment 1, we demonstrated that NB's impairment in making recognition judgments affects cumulative frequency judgments for exposure to concept names in a recent study episode. Experiments 2 and 3 revealed, with a task borrowed from the semantic-memory literature, that NB's impairments do indeed extend to abnormalities in judging cumulative lifetime familiarity for object concepts. These abnormalities were not limited to verbal processing, and were present even when pictures were offered as additional cues. Moreover, they showed sensitivity to concept structure as reflected in semantic feature norms; we only observed them for judgments on object concepts with high feature overlap. In Experiment 4, we found that an amnesic patient (HC) with previously established deficits in autobiographical recollection, due to a selective lesion of the extended hippocampal system, does not exhibit any abnormalities in assessing lifetime familiarity. Together, these findings provide support for a functional link between the assessment of recent changes in familiarity, as probed with experimental study-test paradigms, and cumulative lifetime familiarity based on autobiographical experience accrued outside the laboratory. They argue in favor of the notion that familiarity is closely related to the representation of concept knowledge, likely through computations in perirhinal cortex. PMID- 27378442 TI - Purification of infectious and non-infectious chlamydial particles using iodixanol for density gradient preparation. AB - Chlamydiae are obligate intracellular bacteria with two distinct morphological stages, the infectious elementary bodies (EBs) and non-infectious reticulate bodies (RBs). Here we describe a rapid and straightforward protocol for the purification of EBs and RBs involving special density gradients. It has been successfully applied to three chlamydial species. PMID- 27378443 TI - Hyperspectral interventional imaging for enhanced tissue visualization and discrimination combining band selection methods. AB - PURPOSE: Hyperspectral imaging is an emerging technology recently introduced in medical applications inasmuch as it provides a powerful tool for noninvasive tissue characterization. In this context, a new system was designed to be easily integrated in the operating room in order to detect anatomical tissues hardly noticed by the surgeon's naked eye. METHOD: Our LCTF-based spectral imaging system is operative over visible, near- and middle-infrared spectral ranges (400 1700 nm). It is dedicated to enhance critical biological tissues such as the ureter and the facial nerve. We aim to find the best three relevant bands to create a RGB image to display during the intervention with maximal contrast between the target tissue and its surroundings. A comparative study is carried out between band selection methods and band transformation methods. Combined band selection methods are proposed. All methods are compared using different evaluation criteria. RESULTS: Experimental results show that the proposed combined band selection methods provide the best performance with rich information, high tissue separability and short computational time. These methods yield a significant discrimination between biological tissues. CONCLUSION: We developed a hyperspectral imaging system in order to enhance some biological tissue visualization. The proposed methods provided an acceptable trade-off between the evaluation criteria especially in SWIR spectral band that outperforms the naked eye's capacities. PMID- 27378444 TI - Authors' response to the letter of Nagirnaja et al., "Response to annexin A5 haplotype M2 is not a risk factor for recurrent miscarriages in Northern Europe, is there sufficient evidence?". PMID- 27378445 TI - Pre-Liver Transplant Transthoracic Echocardiogram Findings and 6-Month Post Transplant Outcomes: A Case-Control Analysis. AB - BACKGROUND Cardiopulmonary (CP) outcomes remain a leading cause of morbidity and mortality following liver transplantation (LT). The optimal CP risk stratification of LT candidates remains unclear. The aim of this study was to evaluate the association of pre-LT transthoracic echocardiogram (TTE) findings and 6-month post-LT outcomes. MATERIAL AND METHODS This retrospective review analyzed adults who underwent LT, comparing those who died within 6 months of LT (cases; n=38) with age- and sex-matched patients who survived >6 months (controls; n=38). Cases were categorized by cause of death (COD) defined as either a primary CP process (n=20) or a non-CP process (n=18). Data were analyzed using logistic regression and survival analysis was performed using Kaplan-Meier curves. RESULTS There was a higher odds of death within 6 months of LT with >= mild mitral regurgitation (OR 3.44, p=0.03) or an incomplete assessment of right ventricular systolic function (RVSF) (OR 24, p=0.004). On subgroup analysis, these findings only persisted in patients with a CP COD. Patients with CP COD were older (61 vs. 54.5, p=0.04), had longer intervals between TTE and LT (122 vs. 29 days, p=0.05), less complete assessments of RVSF (p=0.009), and lower RV fractional area change (p=0.04) compared to patients with non-CP COD. CONCLUSIONS Multiple TTE parameters were associated with patients who died within 6 months of LT, and in particular patients with a CP COD. Our findings suggest that pre-LT TTEs can convey useful CP risk stratification information and emphasizes the importance of adequately assessing these parameters prior to LT. PMID- 27378446 TI - [Potential protective role of nitric oxide and Hsp70 linked to functional foods in the atherosclerosis]. AB - Atherosclerosis, one of the main pathologic entities considered epidemic and a worldwide public health problem, is currently under constant review as regards its basic determining mechanisms and therapeutic possibilities. In this regard, all patients afflicted with the disease exhibit mitochondrial dysfunction, oxidative stress and inflammation. Interestingly, nitric oxide - a known vasoactive messenger gas - has been closely related to the inflammatory, oxidative and mitochondrial dysfunctional process that characterizes atherosclerosis. In addition, it has recently been demonstrated that alterations in the bioavailability of nitric oxide would induce the expression of heat shock proteins. This agrees with the use of functional foods as a strategy to prevent both vascular aging and the development of atherosclerosis. Finally, a greater knowledge regarding the mechanisms implied in the development of atherosclerosis will enable proposing new and possible hygiene, health and therapeutic interventions. PMID- 27378448 TI - Can Australian psychiatrists prescribe clozapine off-label for treatment refractory bipolar disorder? PMID- 27378447 TI - HANDS2: accurate assignment of homoeallelic base-identity in allopolyploids despite missing data. AB - Characterization of homoeallelic base-identity in allopolyploids is difficult since homeologous subgenomes are closely related and becomes further challenging if diploid-progenitor data is missing. We present HANDS2, a next-generation sequencing-based tool that enables highly accurate (>90%) genome-wide discovery of homeolog-specific base-identity in allopolyploids even in the absence of a diploid-progenitor. We applied HANDS2 to the transcriptomes of various cruciferous plants belonging to genus Brassica. Our results suggest that the three C genomes in Brassica are more similar to each other than the three A genomes, and provide important insights into the relationships between various Brassica tetraploids and their diploid-progenitors at a single-base resolution. PMID- 27378449 TI - [Intraoperative optical coherence tomography in retinal detachment]. AB - BACKGROUND: Using intraoperative optical coherence tomography (iOCT) can be advantageous during macular surgery and lamellar keratoplasty. It is yet unknown if there is a distinct benefit in its application in retinal detachment surgery. OBJECTIVE: What can be shown using iOCT during retinal detachment surgery? Can therapeutically relevant decisions be made and do they have a prognostic implication on postoperative results? METHODS: Based on already published (11 patients/eyes) and our own new data (23 patients/eyes),findings by iOCT during retinal detachment surgery are presented. RESULTS: Outer retinal corrugations are a frequent feature in iOCT in retinal detachment. These corrugations persist during the application of heavy liquids. Even when the retina seems clinically reattached under the use of perfluoroctane, there is significant subfoveal fluid. Using perfluordecaline, there seems to be less subfoveal fluid. In patients with retinal detachment and macula off situation, subclinical full thickness macular holes seem to be more common than assumed. It is unclear if their incidence is influenced by the use of heavy liquids. They appear to have a negative predictive value regarding postoperative visual acuity. CONCLUSION: Even if there are no obvious benefits in using iOCT in retinal detachment surgery, this new technique offers deeper insights into the microarchitecture of the detached retina. Further investigations in more patients will show if the use of the iOCT will result in a better prognosis for our patients. PMID- 27378450 TI - Evaluation of protective efficacy induced by virus-like particles containing a Trichinella spiralis excretory-secretory (ES) protein in mice. AB - BACKGROUND: The frequent outbreaks of human trichinellosis globally underscore the need to develop effective vaccine. We hypothesized that a novel vaccine could improve vaccine efficacy against Trichinella spiralis. METHODS: In this study, we developed virus-like particles (VLPs) containing the 53 KDa excretory/secretory (ES) protein of T. spiralis and the influenza matrix protein 1 (M1) as a core protein, and investigated the protective efficacy of the VLPs alone or with cholera toxin (CT) in a mouse model. RESULTS: Intramuscular immunization induced T. spiralis-specific IgG, IgG1 and IgG2a antibody responses before and after challenge infections in the sera. These antibody responses were significantly enhanced in mice immunized with adjuvanted VLPs. Upon challenge infection, vaccinated mice showed significantly reduced worm burden in the diaphragm. Protective immune responses and efficacy of protection were significantly improved by immunization with VLPs together with CT adjuvant. CONCLUSIONS: Our results are informative for a better understanding of the protective immunity induced by T. spiralis VLPs, and will provide insight into designing safe and effective vaccines. PMID- 27378452 TI - Oxidative beta-Csp(3) -H Functionalization of tBuOH: A Selective Radical/Radical Cross-Coupling Access to beta-Hydroxy Thioethers. AB - An oxidative beta-Csp(3) -H functionalization of tert-butanol (tBuOH) for the construction of C-S bonds through an iodine-catalyzed Csp(3) -H/S-H coupling was successfully achieved. Different kinds of mercaptans were shown to be good coupling partners, affording the desired products in good yields. This protocol not only offers a novel method for the synthesis of beta-hydroxy thioethers, but also provides an effective strategy for selective radical/radical cross-coupling. PMID- 27378451 TI - Hyperparathyroidism complicating CYP 24A1 mutations. AB - CYP24A1 gene mutations induce infantile hypercalcemia, with high 1,25(OH)2D contrasting with low PTH levels. The adult phenotype is not well known. Two unrelated adult patients were referred for nephrolithiasis, hypertension, hypercalcemia, hypercalciuria, normal 25-OHD levels, and inappropriate PTH levels (22 to 92pg/mL;N: 15-68) suggesting primary hyperparathyroidism, leading to surgery. Hypercalciuria improved despite persistent hypercalcemia, treated with cinacalcet. The ratio 25-OHD3/24-25-(OH)2D3>100 (N<25) suggested the diagnosis of CYP24A1 mutations which were confirmed through Sanger sequencing. In conclusion, the adult phenotype associated with CYP24A1 mutations can evolve over time from hypercalcemia with suppressed PTH towards hyperparathyroidism with moderately increased PTH level, adenoma and/or slightly increased parathyroid glands. Surgery decreased calciuria and improved kidney function. Cinacalcet was partially effective on hypercalcemia since PTH was inappropriate. This novel phenotype, a phenocopy of hyperparathyroidism, might evolve in few cases towards hyperparathyroidism despite random association of the 2 diseases cannot be excluded. PMID- 27378453 TI - Enhancement of Skeletal Muscle in Aged Rats Following High-Intensity Stretch Shortening Contraction Training. AB - Exercise is the most accessible, efficacious, and multifactorial intervention to improve health and treat chronic disease. High-intensity resistance exercise, in particular, also maximizes skeletal muscle size and strength-outcomes crucial at advanced age. However, such training is capable of inducing muscle maladaptation when misapplied at old age. Therefore, characterization of parameters (e.g., mode and frequency) that foster adaptation is an active research area. To address this issue, we utilized a rodent model that allowed training at maximal intensity in terms of muscle activation and tested the hypothesis that muscles of old rats adapt to stretch-shortening contraction (SSC) training, provided the training frequency is sufficiently low. At termination of training, normalized muscle mass (i.e., muscle mass divided by tibia length) and muscle quality (isometric force divided by normalized muscle mass) were determined. For young rats, normalized muscle mass increased by ~20% regardless of training frequency. No difference was observed for muscle quality values after 2 days versus 3 days per week training (0.65 +/- 0.09 N/mg/mm vs. 0.59 +/- 0.05 N/mg/mm, respectively). For old rats following 3 days per week training, normalized muscle mass was unaltered and muscle quality was 30% lower than young levels. Following 2 days per week training at old age, normalized muscle mass increased by 17% and muscle quality was restored to young levels. To investigate this enhanced response, oxidative stress was assessed by lipid peroxidation quantification. For young rats, lipid peroxidation levels were unaltered by training. With aging, baseline levels of lipid peroxidation increased by 1.5-fold. For old rats, only 2 days per week training decreased lipid peroxidation to levels indistinguishable from young values. These results imply that, appropriately scheduled high-intensity SSC training at old age is capable of restoring muscle to a younger phenotype in terms of lipid peroxidation levels and muscle quality. PMID- 27378454 TI - Optic nerve melanocytoma. PMID- 27378455 TI - Congenital optic nerve anomalies. AB - OBJECTIVE: To update the current knowledge about congenital optic disc anomalies. METHODS: A comprehensive literature search was performed in the major biomedical databases. RESULTS: Patients with these anomalies usually have poor vision in infancy. Refractive errors are common, and serous retinal detachment may develop in some of these anomalies. It is critically important to clinically differentiate between these congenital optic disc anomalies, as central nervous system malformations are common in some, whereas others may be associated with systemic anomalies. CONCLUSIONS: Congenital optic disc anomalies are a heterogeneous group of pathologies with characteristic fundus appearance and systemic associations. We should always try to make a correct diagnosis, in order to ask for specific tests, as well as to provide an adequate follow-up. PMID- 27378456 TI - Implications of the anatomical classification of the neovascular form of age related macular degeneration. AB - OBJECTIVE: To present the clinical relevance of the anatomical classification of the neovascular form of Age-Related Macular Degeneration (AMD). METHODS: Critical analysis of the current situation in the management of patients with neovascular AMD, by reviewing the available scientific evidence with regards to the classification of the types of neovascular lesion by angiography and optical coherence tomography (OCT). RESULTS: The classification of the neovascular lesion type secondary to AMD by OCT in type 1 lesions (under the pigment epithelium), type 2 (subretinal), and type 3 (retinal angiomatous proliferation), provides an added value in allowing to establish a long-term visual prognosis, an estimate of the number of treatments that a certain case may require, and a stratification of the risk for secondary geographic atrophy. CONCLUSIONS: Incorporating OCT to the initial qualitative analysis of cases with neovascular AMD offers an added value superior to that provided by the angiography, with the relevant clinical implications. PMID- 27378457 TI - Presumed solitary circumscribed retinal astrocytic proliferation. AB - INTRODUCTION: Presumed solitary circumscribed retinal astrocytic proliferation (PSCRAP) is a small defined solitary lesion. CASE REPORT: A 58-year-old man had an opaque yellow retinal lesion inferonasal to the optic disc. Fluorescein angiography showed mild early hyperfluorescence and late fluorescence. Ultrasound showed no calcification. Autofluorescence disclosed moderate hyperautofluorescence. Optical coherence tomography showed the mass with a snowball configuration and a smooth surface. More than one year later, the lesion was unchanged. DISCUSSION: PSCRAP is a benign stable lesion. The main importance lies in its differentiation from well-circumscribed yellow-white lesions of the retina. PMID- 27378458 TI - Tideglusib, a chemical inhibitor of GSK3beta, attenuates hypoxic-ischemic brain injury in neonatal mice. AB - BACKGROUND: Hypoxia-ischemia is an important cause of brain injury and neurological morbidity in the newborn infants. The activity of glycogen synthase kinase-3beta (GSK-3beta) is up-regulated following neonatal stroke. Tideglusib is a GSK-3beta inhibitor which has neuroprotective effects against neurodegenerative diseases in clinical trials. However, the effect of tideglusib on hypoxic ischemic (HI) brain injury in neonates is still unknown. METHODS: Postnatal day 7 (P7) mouse pups subjected to unilateral common carotid artery ligation followed by 1h of hypoxia or sham surgery was performed. HI animals were administered tideglusib (5mg/kg) or vehicle intraperitoneally 20min prior to the onset of ischemia. The brain infarct volume and whole brain images, were used in conjunction with Nissl staining to evaluate the protective effects of tideglusib. Protein levels of glial fibrillary acidic protein (GFAP), Notch1, cleaved caspase 3/9, phosphorylated signal transducer and activator of transcription 3 (STAT3), GSK-3beta and protein kinase B (Akt) were detected to identify potentially involved molecules. RESULTS: Tideglusib significantly reduced cerebral infarct volume at both 24h and 7days after HI injury. Tideglusib also increased phosphorylated GSK-3beta(Ser9) and Akt(Ser473), and reduced the expression of GFAP and p-STAT3(Tyr705). In addition, pretreatment with tideglusib also enhanced the protein level of Notch1. Moreover, tideglusib reduced the cleavage of pro apoptotic signal caspase proteins, including caspase 3 and caspase 9 following HI. CONCLUSION: These results indicate that tideglusib shows neuroprotection against hypoxic-ischemic brain injury in neonatal mice. GENERAL SIGNIFICANCE: Tideglusib is a potential compound for the prevention or treatment of hypoxic ischemic brain injury in neonates. PMID- 27378460 TI - Optimism for prison syringe programs. PMID- 27378459 TI - The physicochemical properties of membranes correlate with the NADPH oxidase activity. AB - BACKGROUND: Phagocytes kill ingested microbes by exposure to high concentrations of toxic reactive species generated by NADPH-oxidases. This membrane-bound electron-transferring enzyme is tightly regulated by cellular signaling cascades. So far, molecular and biophysical studies of the NADPH-oxidase were performed over limited temperature ranges, which weaken our understanding of immune response or inflammatory events. In this work, we have inspected the influence of temperature and lipid membrane properties on the NADPH-oxidase activity using a system free of cell complexity. METHODS: We have extended the experimental conditions of the accepted model for NADPH-oxidase activity, the so-called cell free assay, to a large temperature range (10-40 degrees C) using different membrane compositions (subcellular compartments or liposomes). RESULTS: A remarkable increase of superoxide production rate was observed with rising temperature. Synchrotron radiation circular dichroism data showed that this is not correlated with protein secondary structure changes. When lipid bilayers are in fluid phase, Arrhenius plots of the oxidase activity showed linear relationships with small activation energy (Ea), while when in solid phase, high Ea was found. The sterol content modulates kinetic and thermodynamic parameters. CONCLUSION: High temperature promotes the rate of superoxide production. The key element of this enhancement is related to membrane properties such as thickness and viscosity and not to protein structural changes. Membrane viscosity that can be driven by sterols is a paramount parameter of Ea of NADPH oxidase activity. The membrane bilayer state modulated by its sterol content may be considered locally as an enzyme regulator. This article is part of a Special Issue entitled "Science for Life" Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazu and Dr. Federica Migliardo. PMID- 27378461 TI - Critical illness polyneuromyopathy. PMID- 27378462 TI - Intensive lowering of blood pressure: Should we SPRINT? PMID- 27378463 TI - Canada's emergency medicine shortfall. PMID- 27378464 TI - Development of the Canadian Syncope Risk Score to predict serious adverse events after emergency department assessment of syncope. AB - BACKGROUND: Syncope can be caused by serious conditions not evident during initial evaluation, which can lead to serious adverse events, including death, after disposition from the emergency department. We sought to develop a clinical decision tool to identify adult patients with syncope who are at risk of a serious adverse event within 30 days after disposition from the emergency department. METHODS: We prospectively enrolled adults (age >= 16 yr) with syncope who presented within 24 hours after the event to 1 of 6 large emergency departments from Sept. 29, 2010, to Feb. 27, 2014. We collected standardized variables at index presentation from clinical evaluation and investigations. Adjudicated serious adverse events included death, myocardial infarction, arrhythmia, structural heart disease, pulmonary embolism, serious hemorrhage and procedural interventions within 30 days. RESULTS: We enrolled 4030 patients with syncope; the mean age was 53.6 years, 55.5% were women, and 9.5% were admitted to hospital. Serious adverse events occurred in 147 (3.6%) of the patients within 30 days after disposition from the emergency department. Of 43 candidate predictors examined, we included 9 in the final model: predisposition to vasovagal syncope, heart disease, any systolic pressure reading in the emergency department < 90 or > 180 mm Hg, troponin level above 99th percentile for the normal population, abnormal QRS axis (< -30 degrees or > 100 degrees ), QRS duration longer than 130 ms, QTc interval longer than 480 ms, emergency department diagnosis of cardiac syncope and emergency department diagnosis of vasovagal syncope (C statistic 0.88, 95% confidence interval [CI] 0.85-0.90; optimism 0.015; goodness of-fit p = 0.11). The risk of a serious adverse event within 30 days ranged from 0.4% for a score of -3 to 83.6% for a score of 11. The sensitivity was 99.2% (95% CI 95.9%-100%) for a threshold score of -2 or higher and 97.7% (95% CI 93.5% 99.5%) for a threshold score of -1 or higher. INTERPRETATION: The Canadian Syncope Risk Score showed good discrimination and calibration for 30-day risk of serious adverse events after disposition from the emergency department. Once validated, the tool will be able to accurately stratify the risk of serious adverse events among patients presenting with syncope, including those at low risk who can be discharged home quickly. PMID- 27378465 TI - Methodologic approaches to evaluating new highly sensitive diagnostic tests: avoiding overdiagnosis. PMID- 27378466 TI - Indigenous health: Time for top-down change? PMID- 27378467 TI - Effect of human papillomavirus vaccination on cervical cancer screening in Alberta. AB - BACKGROUND: A school-based program with quadrivalent human papillomavirus (HPV) vaccination was implemented in Alberta in 2008. We assessed the impact of this program on Pap test cytology results using databases of province-wide vaccination and cervical cancer screening. METHODS: We conducted a nested case-control study involving a cohort of women in Alberta born between 1994 and 1997 who had at least 1 Pap test between 2012 and 2015. Women with negative cytology results were controls. Women with low-grade (atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion) and high-grade (atypical squamous cells, cannot rule out a high-grade lesion; or high-grade squamous intraepithelial lesion) cervical abnormalities were cases. Exposure status was assigned according to records of HPV vaccination. Odds ratios (ORs) for abnormal cytology results by vaccination status were adjusted for neighbourhood income, laboratory service, rural versus urban residency, and age. RESULTS: The total study population was 10 204. Adjusting for age, vaccinated women had a higher screening rate than unvaccinated women (13.0% v. 11.4%, p < 0.001). Among women who received full vaccination (>= 3 doses), the adjusted OR for cervical abnormalities was 0.72 (95% confidence interval [CI] 0.63-0.82). For high-grade lesions, the adjusted OR was 0.50 (95% CI 0.30-0.85). With 2-dose HPV vaccination, the adjusted OR for cervical abnormalities was 1.08 (95% CI 0.84 1.38). INTERPRETATION: Quadrivalent HPV vaccination significantly reduced high grade cervical abnormalities but required 3 doses. Vaccination against HPV was associated with screening uptake. Population-based vaccination and screening programs should work together to optimize cervical cancer prevention. PMID- 27378468 TI - Organizational factors associated with Health Care Provider (HCP) influenza campaigns in the Veterans health care system: a qualitative study. AB - BACKGROUND: It is an important goal to vaccinate a high proportion of health care providers (HCPs) against influenza, to prevent transmission to patients. Different aspects of how a HCP vaccination campaign is conducted may be linked to different vaccination rates. We sought to characterize organizational factors and practices that were associated with vaccination campaign success among six sites within the Veterans Health Administration, where receipt of flu-vaccination is voluntary. METHOD: We conducted a total of 31 telephone interviews with key informants who were involved with HCP flu vaccination campaigns at three sites with high-vaccination rates and three sites with low-vaccination rates. We compared the organization and management of the six sites' campaigns using constant comparison methods, characterzing themes and analyzing data iteratively. RESULTS: Three factors distinguished sites with high flu vaccination rates from those with low vaccination rates. 1) High levels of executive leadership involvement: demonstrating visible support, fostering new ideas, facilitating resources, and empowering flu team members; 2) Positive flu team characteristics: high levels of collaboration, sense of campaign ownership, sense of empowerment to meet challenges, and adequate time and staffing dedicated to the campaign; and 3) Several concrete strong practices emerged: advance planning, easy access to the vaccine, ability to track employee vaccination status, use of innovative methods to educate staff, and use of audit and feedback to promote targeted efforts to reach unvaccinated employees. CONCLUSION: Successful HCP flu campaigns shared several recognizable characteristics, many of which are amenable to adoption or emulation by programs hoping to improve their vaccination rates. PMID- 27378469 TI - Metalloproteases meprin-alpha (MEP1A) is a prognostic biomarker and promotes proliferation and invasion of colorectal cancer. AB - BACKGROUND: Meprin displays multiple functions in both health and disease, due in part to its broad proteolytic activity. In this report, we explored the clinical significance and functional relevance of the expression of meprin-alpha (MEP1A) in colorectal cancer (CRC). METHODS: The mRNA and protein expression levels of MEP1A in tumor specimens obtained from CRC patients was determined by quantitative real-time PCR and Western blot assay and comparatively paired with adjacent mucosa that presented as normal tissue. ShRNA was used to knock-down MEP1A expression in CRC cell-lines and the effects of dampened expression of MEP1A on the proliferation and invasion were determined by colony formation assays, Cell Counting Kit-8 assays and matrigel invasion assays. Moreover, nude mouse xenograft models were designed to investigate the same effect in vivo. In order to determine whether MEP1A expression correlated with CRC clinicopathologic factors and survival, immunohistochemical staining of a tissue microarray containing 88 paired CRC specimens was performed. RESULTS: In CRC, enhanced expression of MEP1A was seen. Additionally, both in vitro and in vivo, CRC cellular proliferation and invasiveness was inhibited by dampened MEP1A expression. Several parameters were associated with enhanced MEP1A expression including tumor size (P = 0.023), staging of CRC by the American Joint Committee on Cancer (AJCC) (P = 0.024), and T (P = 0.032) and N stages (P = 0.001). Moreover, the expression of MEP1A is an independent prognostic factor for overall survival in CRC (HR 3.643; 95 % CI 0.305-5.842; P = 0.007). CONCLUSION: MEP1A was not only found to be functionally important, but it might also serve as an important and unique indicator of patient prognosis and therapeutic targeting in CRC. PMID- 27378471 TI - Erratum: Embryonic transcription is controlled by maternally defined chromatin state. PMID- 27378470 TI - Process evaluation of two participatory approaches: Implementing total worker health(r) interventions in a correctional workforce. AB - BACKGROUND: Correctional Officers (COs) have among the highest injury rates and poorest health of all the public safety occupations. The HITEC-2 (Health Improvement Through Employee Control-2) study uses Participatory Action Research (PAR) to design and implement interventions to improve health and safety of COs. METHOD: HITEC-2 compared two different types of participatory program, a CO-only "Design Team" (DT) and "Kaizen Event Teams" (KET) of COs and supervisors, to determine differences in implementation process and outcomes. The Program Evaluation Rating Sheet (PERS) was developed to document and evaluate program implementation. RESULTS: Both programs yielded successful and unsuccessful interventions, dependent upon team-, facility-, organizational, state-, facilitator-, and intervention-level factors. CONCLUSIONS: PAR in corrections, and possibly other sectors, depends upon factors including participation, leadership, continuity and timing, resilience, and financial circumstances. The new PERS instrument may be useful in other sectors to assist in assessing intervention success. Am. J. Ind. Med. 59:897-918, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27378472 TI - Triglyceride-rich lipoprotein metabolism in women: roles of apoC-II and apoC-III. AB - BACKGROUND: Experimental data suggest that apolipoprotein (apo) C-II and C-III regulate triglyceride-rich lipoprotein (TRL) metabolism, but there are limited studies in humans. We investigated the metabolic associations of TRLs with apoC II and apoC-III concentrations and kinetics in women. MATERIAL AND METHODS: The kinetics of plasma apoC-II, apoC-III and very low-density lipoprotein (VLDL) apoB 100 and triglycerides were measured in the postabsorptive state using stable isotopic techniques and compartmental modelling in 60 women with wide-ranging body mass index (19.5-32.9 kg/m(2) ). RESULTS: Plasma apoC-II and apoC-III concentrations were positively associated with the concentrations of plasma triglycerides, VLDL1 - and VLDL2 -apoB-100 and triglyceride (all P < 0.05). ApoC II production rate (PR) was positively associated with VLDL1 -apoB-100 concentration, VLDL1 triglyceride concentration and VLDL1 triglyceride PR, while apoC-II fractional catabolic rate (FCR) was positively associated with VLDL1 triglyceride FCR (all P < 0.05). No significant associations were observed between apoC-II and VLDL2 apoB-100 or triglyceride kinetics. ApoC-III PR, but not FCR, was positively associated with VLDL1 triglyceride, and VLDL2 -apoB-100 and triglyceride concentrations (all P < 0.05). No significant associations were observed between apoC-III and VLDL-apoB-100 and triglyceride kinetics. In multivariable analysis, including homoeostasis model assessment score, menopausal status and obesity, apoC-II concentration was significantly associated with plasma triglyceride, VLDL1 -apoB-100 and VLDL1 triglyceride concentrations and PR. Using the same multivariable analysis, apoC-III was significantly associated with plasma triglyceride and VLDL1 - and VLDL2 -apoB-100 and triglyceride concentrations and FCR. CONCLUSIONS: In women, plasma apoC-II and apoC-III concentrations are regulated by their respective PR and are significant, independent determinants of the kinetics and plasma concentrations of TRLs. PMID- 27378473 TI - Fourth consensus of the International Society for Premenstrual Disorders (ISPMD): auditable standards for diagnosis and management of premenstrual disorder. AB - Whilst professional bodies such as the Royal College and the American College of Obstetricians and Gynecologists have well-established standards for audit of management for most gynaecology disorders, such standards for premenstrual disorders (PMDs) have yet to be developed. The International Society of Premenstrual Disorders (ISPMD) has already published three consensus papers on PMDs covering areas that include definition, classification/quantification, clinical trial design and management (American College Obstetricians and Gynecologists 2011; Brown et al. in Cochrane Database Syst Rev 2:CD001396, 2009; Dickerson et al. in Am Fam Physician 67(8):1743-1752, 2003). In this fourth consensus of ISPMD, we aim to create a set of auditable standards for the clinical management of PMDs. All members of the original ISPMD consensus group were invited to submit one or more auditable standards to be eligible in the inclusion of the consensus. Ninety-five percent of members (18/19) responded with at least one auditable standard. A total of 66 auditable standards were received, which were returned to all group members who then ranked the standards in order of priority, before the results were collated. Proposed standards related to the diagnosis of PMDs identified the importance of obtaining an accurate history, that a symptom diary should be kept for 2 months prior to diagnosis and that symptom reporting demonstrates symptoms in the premenstrual phase of the menstrual cycle and relieved by menstruation. Regarding treatment, the most important standards were the use of selective serotonin reuptake inhibitors (SSRIs) as a first line treatment, an evidence-based approach to treatment and that SSRI side effects are properly explained to patients. A set of comprehensive standards to be used in the diagnosis and treatment of PMD has been established, for which PMD management can be audited against for standardised and improved care. PMID- 27378474 TI - Serum metabolites predict response to angiotensin II receptor blockers in patients with diabetes mellitus. AB - BACKGROUND: Individual patients show a large variability in albuminuria response to angiotensin receptor blockers (ARB). Identifying novel biomarkers that predict ARB response may help tailor therapy. We aimed to discover and validate a serum metabolite classifier that predicts albuminuria response to ARBs in patients with diabetes mellitus and micro- or macroalbuminuria. METHODS: Liquid chromatography tandem mass spectrometry metabolomics was performed on serum samples. Data from patients with type 2 diabetes and microalbuminuria (n = 49) treated with irbesartan 300 mg/day were used for discovery. LASSO and ridge regression were performed to develop the classifier. Improvement in albuminuria response prediction was assessed by calculating differences in R(2) between a reference model of clinical parameters and a model with clinical parameters and the classifier. The classifier was externally validated in patients with type 1 diabetes and macroalbuminuria (n = 50) treated with losartan 100 mg/day. Molecular process analysis was performed to link metabolites to molecular mechanisms contributing to ARB response. RESULTS: In discovery, median change in urinary albumin excretion (UAE) was -42 % [Q1-Q3: -69 to -8]. The classifier, consisting of 21 metabolites, was significantly associated with UAE response to irbesartan (p < 0.001) and improved prediction of UAE response on top of the clinical reference model (R(2) increase from 0.10 to 0.70; p < 0.001). In external validation, median change in UAE was -43 % [Q1-Q35: -63 to -23]. The classifier improved prediction of UAE response to losartan (R(2) increase from 0.20 to 0.59; p < 0.001). Specifically ADMA impacting eNOS activity appears to be a relevant factor in ARB response. CONCLUSIONS: A serum metabolite classifier was discovered and externally validated to significantly improve prediction of albuminuria response to ARBs in diabetes mellitus. PMID- 27378475 TI - A pathophysiology-based approach to the diagnosis and treatment of lupus nephritis. AB - Lupus is no longer an unknown chameleon of medicine. Significant progress has been made on unraveling the pathogenesis of lupus and lupus nephritis, and how to treat the disease. Here we provide an update on the pathophysiology of lupus and its related kidney disease, consider areas of controversy in disease management, and discuss the unmet needs of lupus nephritis and how to address these needs. We focus on rethinking how innovative therapies for lupus nephritis should be evaluated and evolving strategies to more efficiently mitigate irreversible nephron loss in patients with lupus nephritis. PMID- 27378477 TI - Lateral approach for sinus floor elevation: large versus small bone window - a split-mouth randomized clinical trial. AB - OBJECTIVES: To test whether a reduction of bone window dimension, in a split mouth randomized study design, focused on lateral sinus floor elevations, can achieve better results than a wider window in terms of augmented bone height and a reduction of patient discomfort and surgical complications. MATERIALS AND METHODS: Of the sixteen subjects enrolled in the study, each underwent a bilateral sinus lift procedure based on two different access flaps to maxillary sinus. Test side: small access window (6 * 6 mm) + bone filling using a special device. Control side: large access window (10 * 8 mm) + manual bone filling. Alveolar bone height and width were measured at pre-op and 6-month post-op CT scans; repeatable measurements were obtained using radiographic stents. Surgical intervention duration was also recorded. Patients' evaluation of surgical discomfort was assessed using a VAS diagram at 7-day, 14-day and 30-day follow up. RESULTS: A significant bone augmentation in height and width of alveolar crest was obtained in both test (8.71 +/- 1.11 mm, 4.70 +/- 0.58 mm) and control (8.5 +/- 2.02 mm, 4.68 +/- 0.70 mm) sides, although no significant differences were found between the two groups. Neither any significant differences emerge in data concerning the duration of the intervention (Test 42.62 +/- 6.67 min, Control 41.68 +/- 8.34 min). Patients' opinion relating to surgical discomfort showed a preference for test procedure at 7-day, 14-day and 30-day follow-up. CONCLUSIONS: A reduction of window dimensions did not affect the safety of the surgical procedure. The two testing techniques showed no statistically significant differences in surgical intervention duration. Patients' opinion at 7 day and 14-day post-op showed a preference for test procedure. PMID- 27378476 TI - Human mannose-binding lectin inhibitor prevents Shiga toxin-induced renal injury. AB - Hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli (STEC HUS) is a worldwide endemic problem, and its pathophysiology is not fully elucidated. Here we tested whether the mannose-binding lectin (MBL2), an initiating factor of lectin complement pathway activation, plays a crucial role in STEC HUS. Using novel human MBL2-expressing mice (MBL2 KI) that lack murine Mbls (MBL2(+/+)Mbl1(-/-)Mbl2(-/-)), a novel STEC HUS model consisted of an intraperitoneal injection with Shiga toxin-2 (Stx-2) with or without anti-MBL2 antibody (3F8, intraperitoneal). Stx-2 induced weight loss, anemia, and thrombocytopenia and increased serum creatinine, free serum hemoglobin, and cystatin C levels, but a significantly decreased glomerular filtration rate compared with control/sham mice. Immunohistochemical staining revealed renal C3d deposition and fibrin deposition in glomeruli in Stx-2-injected mice. Treatment with 3F8 completely inhibited serum MBL2 levels and significantly attenuated Stx 2 induced-renal injury, free serum hemoglobin levels, renal C3d, and fibrin deposition and preserved the glomerular filtration rate. Thus, MBL2 inhibition significantly protected against complement activation and renal injury induced by Stx-2. This novel mouse model can be used to study the role of complement, particularly lectin pathway-mediated complement activation, in Stx-2-induced renal injury. PMID- 27378478 TI - beta-Pyrrolopyrazino Annulated Corroles via a Pictet-Spengler Approach. AB - Reaction of 2-amino-3-(pyrrol-1-yl)-5,10,15-tris(4-tert-butylphenyl)corrolato copper(II) with arylaldehydes affords novel pi-extended beta,beta'-pyrrolo(1,2 a)pyrazino-fused corroles via a Pictet-Spengler reaction. Corrole shows an unprecedented reaction pathway, leading to a mixture of phenyl-substituted and nonsubstituted pyrrolopyrazino annulated species as reaction products. PMID- 27378480 TI - Sublethal effects of pulp and paper mill effluent on two commonly cultured carps: a SEM- and EDS-based hematological biomarker analysis. AB - Blood being a vehicle for the transport of industrial pollutants in living system, fish hematology is considered as potent biomarker. In the present study, we investigated respective sublethal effects of pulp and paper mill effluents on hematology of two commonly cultured carps, Cyprinus carpio and Ctenopharyngodon idella, using optical, scanning electron microscopy and energy-dispersive X-ray spectroscopy. Irrespective of species, results showed significant decrease in erythrocyte, hematocrit and hemoglobin contents while an increase in white blood cell counts (P < 0.05). We observed an increasing trend of MCV (170.0 +/- 3.07 to 193.16 +/- 2.5) and MCH (34.31 +/- 1.89 to 38.71 +/- 3.61) up to 28th day in C. carpio (P < 0.05), while, in C. idella, the highest percent increase in MCV (180.8 +/- 2.19) and MCH (32.9 +/- 0.62) was observed on seventh exposure day, which subsequently declined, respectively, to 173.1 +/- 17.1 and 27.9 +/- 2.45 on 28th day. Unlike C. carpio, significant and progressive MCHC declining trend (18.23 +/- 0.28 to 16.13 +/- 0.31) was observed in C. idella. The most commonly observed abnormalities under SEM include echinocytes, cytoplasmic blebbing, cytoplasmic ring, spherocytes, lobopodial projections and acanthocytes in red blood cells of exposed fishes. EDS further revealed the presence of aluminum, antimony, arsenic, cadmium, mercury, tungsten, zinc and titanium; some of these metals were not even detected in the effluent samples, suggesting the probable metal bio-concentration in fish tissue, and subsequent jeopardization is a major concern particularly in the industrial area. Our study further suggested the use of sensitive and specific techniques like SEM and EDS in fish hematological biomarker analysis along with the conventional approach. PMID- 27378481 TI - Successful Use of Four Factor-Prothrombin Complex Concentrate for Congenital Factor X Deficiency in the Setting of Neurosurgery. AB - Congenital factor X deficiency is an extremely rare coagulation disorder that can place patients at risk for spontaneous hemorrhage or excessive bleeding in the setting of trauma or invasive procedures. Given the rarity of this disorder, there is little published guidance on how best to prevent or treat bleeding. Herein, we report a case of a 56-year-old white man with congenital factor X deficiency who was scheduled for major neurosurgery and who was treated perioperatively with 4-factor prothrombin complex concentrate (4F-PCC). Doses of 4F-PCC at 15 U per kg, administered immediately preoperatively and once at 24 hours postoperatively, allowed for successful completion of an anterior cervical discectomy and fusion without excessive bleeding. Moreover, no thromboembolic complications were observed. As such, given the wide availability of 4F-PCC, it may be considered as a first-line therapy and an alternative to fresh frozen plasma for factor X deficiencies, particularly in high-risk operative cases. PMID- 27378479 TI - Specific miRNA Disease Biomarkers in Blood, Serum and Plasma: Challenges and Prospects. AB - Significant effort has been devoted to discovering microRNA (miRNA) disease biomarkers. In particular, miRNAs in whole blood or specific blood components are candidates for improving the diagnosis of diseases, including life-threatening pathologies. This review covers the challenges crucial for the translation of miRNAs in body fluids (circulating miRNAs) from a research setting into a clinical care scenario. First, we discuss the specificity of miRNA biomarkers for the diagnosis of a disease. While single miRNAs such as miR-20a, miR-21, miR-155, and miR-126 are frequently not disease specific, miRNA signatures that consist of a plurality of different miRNAs may help to improve differentiation between pathologies. Second, we discuss the degree of reproducibility and highlight selected validation studies. While single miRNA markers are often confirmed by independent studies, miRNA signatures are less frequently verified. Third, we address challenges to the profiling of miRNAs in high-throughput settings and we discuss the appropriateness of various analytical platforms and bioinformatics towards a clinical application of miRNAs. Finally, we shed light on the suitability of enriched miRNA sources, e.g. fractionation of body fluids for extracellular vesicles such as exosomes or blood cells, to develop miRNA signatures. With an increasing number of verified miRNA signatures and with the advance of matured medium-throughput approaches in clinical settings, specific miRNA markers are increasingly likely to contribute to human healthcare. PMID- 27378483 TI - Erratum. PMID- 27378482 TI - Pasteurella multocida Bacteremia With Associated Knee Arthroplasty Infection in an 80-Year-Old Caucasian Man. AB - OBJECTIVES: To identify the gram-negative rods grown from blood cultures and a right-knee fluid aspirate from an 80-year-old caucasian man who had undergone a total right knee arthroplastic procedure 6 years ago, and to assess the genetic similarity between the 2 isolates. METHODS: We used 3 different approaches: biochemical testing, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, and 16S ribosomal RNA (rRNA) gene sequencing. RESULTS: The 3 methods identified the gram-negative rods as Pasteurella multocida; 16S rRNA gene sequencing further identified the organisms as P. multocida subsp. septica. CONCLUSION: A concordant identification of P. multocida was observed using biochemical testing, mass spectrometry, and 16S rRNA gene sequencing. Only 16S rRNA sequencing was able to determine the subspecies of P. multocida and to determine the genetic relatedness of the 2 isolates. PMID- 27378484 TI - Regulation of size and uniformity of In2O3 nanooctahedra. AB - Rational regulation of the size and uniformity of nanoparticles has drawn great interests and shown widespread application, but this cannot be simply achieved by the vapor route. In this work, by adopting a chemical vapor deposition approach, the growth process was intricately regulated to guide the reagent supersaturation, and the large-scale growth of uniform-sized In2O3 nanooctahedra was realized. A one-time nucleation and synchronous growth mode controlled by the reagent supersaturation ratio is proposed to be responsible for the uniformity of size. Furthermore, a series of comparative experiments were conducted to study the size dependence on reaction duration, and temperature difference between the heating and depositing zones. This study demonstrates a feasible approach to prepare uniform-sized nanoparticles through precisely controlling the crystal growth process, and the developed growth strategy could be generalized to synthesize uniform-sized nanostructures of other material systems. PMID- 27378487 TI - Vitamin D status in healthy Moroccan men and women aged 50 years and older: a cross-sectional study. AB - This study aimed to compare the vitamin D status in healthy Moroccan men and women aged 50 years and older. A total of 186 Moroccan women and 68 men, who had no previous diagnosis of osteoporosis, were recruited prospectively. We found in this study a high prevalence of hypovitaminosis D with no difference between men and women. PURPOSE: The main purpose of this study was to describe and compare the vitamin D status, parathormone, calcium, and phosphate of healthy Moroccan men and women aged 50 years and older. METHODS: We conducted two cross-sectional studies, in postmenopausal women from October 2008 to November 2009 and in men over 50 years old, from December 2009 to August 2010. A total of 186 Moroccan women and 68 men, who had no previous diagnosis of osteoporosis, were recruited prospectively. For the definition of hypovitaminosis D, the preferred level for 25-hydroxyvitamin D (25(OH)D) insufficiency, which is now recommended by many experts, is 30 ng/mL (75 nmol/L), and the levels below 10 ng/ml (25 nmol/L) indicate deficiency. RESULTS: The prevalence of vitamin D deficiency in men and women was 4.4 and 8.6 %, respectively, and the prevalence of vitamin D(25(OH) D) insufficiency in men and women were 85.2 and 77.4 %, respectively. In men and women, no correlations were found between intact parathormone (PTHi) and 25(OH) D (r = 0.056). CONCLUSIONS: Despite a sunny environment, we found in this study a high prevalence of hypovitaminosis D (insufficiency + deficiency) in Moroccan men over 50 years old and postmenopausal women. PMID- 27378486 TI - Surrogate and clinical endpoints in interventional cardiology: are statistics the brakes? AB - BACKGROUND: Randomized controlled trials are the gold standard for demonstrating safety and efficacy of coronary devices with or without accompanying drug treatments in interventional cardiology. With the advent of last-generation drug eluting stents having enhanced technical attributes and long-term clinical benefits, the proof of incremental angiographic or long-term clinical efficacy becomes more challenging. The purpose of this review is to provide an overview of the most common and alternative study endpoints in interventional cardiology and their potential reimbursement value. Moreover, we intend to describe the statistical limitations in order to demonstrate differences between potential treatment groups. Furthermore, careful endpoint recommendations for a given patient number are offered for future study designs. METHODS: The number of patients per treatment group was estimated for various study designs such as noninferiority test hypotheses with hard clinical endpoints and various surrogate endpoints. To test for differences in various surrogate endpoint scenarios, the corresponding patient group sizes were explored. To evaluate these endpoints in terms of their reimbursement impact, preferred endpoints for technical appraisals in interventional cardiology at the National Institute of Health and Care Excellence (NICE) were used. RESULTS: Even with the most stringent experimental control to reduce bias-introducing factors, studies with hard primary clinical endpoints such as the occurrence of major adverse cardiac events (MACE) or target lesion revascularization (TLR) rates remain the gold standard, with numbers reaching into the 300-700 patient range per group. Study designs using loss in fractional-flow reserve (FFR) or stent-strut-coverage rates can be statistically formulated; however, the clinical ramifications for the patient remain to be discussed. Nonrandomized study designs with intrapatient angiographic controls in nontarget vessels may merit further thoughts and explorations. CONCLUSIONS: From a reimbursement impact, the primary endpoints MACE and TLR are the best choices for a moderately sized study population of 500 patients per group. Angiographic endpoints, in particular minimal lumen diameter (MLD), are not useful in this context. The emerging endpoints such as loss in FFR or stent coverage require smaller patient populations. However, their impact on reimbursement-related decisions is limited. PMID- 27378485 TI - Ageing and ocular surface immunity. AB - The prevalence of ocular surface immunopathologies is enhanced in the elderly. This increased prevalence has been attributed to age-related dysregulation of innate and adaptive immune system responses. Age-related changes in ocular surface immunity have similar and distinct characteristics to those changes seen in other mucosal tissues. This mini review provides a brief outline of key findings in the field of ocular ageing, draws comparisons with other mucosal tissues and, finally, discusses age-related changes in the context of immunopathogenesis of infectious keratitis and dry eye disease, two of the most common inflammatory disorders of the ocular surface. PMID- 27378488 TI - Learning words during shared book reading: The role of extratextual talk designed to increase child engagement. AB - Shared book reading (SBR) is a valuable context for word learning during early childhood, and adults' extratextual talk boosts the vocabulary building potential of SBR. We propose that the benefits of such talk depend largely on a reader's success in promoting children's active engagement (attention and interest) during SBR. When readers ask children questions about new words, especially if they respond to children in a prompt, contingent, and appropriate (positive) manner, this verbal responsiveness functions as an effective engagement strategy. We randomly assigned 3- and 4-year-olds to three reading conditions (low, moderate, and high) distinguished by the degree to which the reader used extratextual engagement strategies, including verbal responsiveness. Despite equal exposure to unfamiliar target words, children's performance improved on two measures of word learning across the three conditions, demonstrating the value of engagement strategies in extratextual talk. This study provides a strong experimental demonstration that adult verbal responsiveness directly benefits preschoolers' word learning. PMID- 27378489 TI - Chloroplast genome structure in Ilex (Aquifoliaceae). AB - Aquifoliaceae is the largest family in the campanulid order Aquifoliales. It consists of a single genus, Ilex, the hollies, which is the largest woody dioecious genus in the angiosperms. Most species are in East Asia or South America. The taxonomy and evolutionary history remain unclear due to the lack of a robust species-level phylogeny. We produced the first complete chloroplast genomes in this family, including seven Ilex species, by Illumina sequencing of long-range PCR products and subsequent reference-guided de novo assembly. These genomes have a typical bicyclic structure with a conserved genome arrangement and moderate divergence. The total length is 157,741 bp and there is one large single copy region (LSC) with 87,109 bp, one small single-copy with 18,436 bp, and a pair of inverted repeat regions (IR) with 52,196 bp. A total of 144 genes were identified, including 96 protein-coding genes, 40 tRNA and 8 rRNA. Thirty-four repetitive sequences were identified in Ilex pubescens, with lengths >14 bp and identity >90%, and 11 divergence hotspot regions that could be targeted for phylogenetic markers. This study will contribute to improved resolution of deep branches of the Ilex phylogeny and facilitate identification of Ilex species. PMID- 27378490 TI - Active cycle of breathing technique for cystic fibrosis. AB - BACKGROUND: People with cystic fibrosis experience chronic airway infections as a result of mucus build up within the lungs. Repeated infections often cause lung damage and disease. Airway clearance therapies aim to improve mucus clearance, increase sputum production, and improve airway function. The active cycle of breathing technique (also known as ACBT) is an airway clearance method that uses a cycle of techniques to loosen airway secretions including breathing control, thoracic expansion exercises, and the forced expiration technique. This is an update of a previously published review. OBJECTIVES: To compare the clinical effectiveness of the active cycle of breathing technique with other airway clearance therapies in cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 25 April 2016. SELECTION CRITERIA: Randomised or quasi-randomised controlled clinical studies, including cross-over studies, comparing the active cycle of breathing technique with other airway clearance therapies in cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two review authors independently screened each article, abstracted data and assessed the risk of bias of each study. MAIN RESULTS: Our search identified 62 studies, of which 19 (440 participants) met the inclusion criteria. Five randomised controlled studies (192 participants) were included in the meta-analysis; three were of cross-over design. The 14 remaining studies were cross-over studies with inadequate reports for complete assessment. The study size ranged from seven to 65 participants. The age of the participants ranged from six to 63 years (mean age 22.33 years). In 13 studies, follow up lasted a single day. However, there were two long-term randomised controlled studies with follow up of one to three years. Most of the studies did not report on key quality items, and therefore, have an unclear risk of bias in terms of random sequence generation, allocation concealment, and outcome assessor blinding. Due to the nature of the intervention, none of the studies blinded participants or the personnel applying the interventions. However, most of the studies reported on all planned outcomes, had adequate follow up, assessed compliance, and used an intention-to-treat analysis.Included studies compared the active cycle of breathing technique with autogenic drainage, airway oscillating devices, high frequency chest compression devices, conventional chest physiotherapy, and positive expiratory pressure. Preference of technique varied: more participants preferred autogenic drainage over the active cycle of breathing technique; more preferred the active cycle of breathing technique over airway oscillating devices; and more were comfortable with the active cycle of breathing technique versus high frequency chest compression. No significant difference was seen in quality of life, sputum weight, exercise tolerance, lung function, or oxygen saturation between the active cycle of breathing technique and autogenic drainage or between the active cycle of breathing technique and airway oscillating devices. There was no significant difference in lung function and the number of pulmonary exacerbations between the active cycle of breathing technique alone or in conjunction with conventional chest physiotherapy. All other outcomes were either not measured or had insufficient data for analysis. AUTHORS' CONCLUSIONS: There is insufficient evidence to support or reject the use of the active cycle of breathing technique over any other airway clearance therapy. Five studies, with data from eight different comparators, found that the active cycle of breathing technique was comparable with other therapies in outcomes such as participant preference, quality of life, exercise tolerance, lung function, sputum weight, oxygen saturation, and number of pulmonary exacerbations. Longer term studies are needed to more adequately assess the effects of the active cycle of breathing technique on outcomes important for people with cystic fibrosis such as quality of life and preference. PMID- 27378491 TI - G protein-coupled estrogen receptor enhances melanogenesis via cAMP-protein kinase (PKA) by upregulating microphthalmia-related transcription factor tyrosinase in melanoma. AB - OBJECTIVE: This study investigated the role and mechanism of action of G protein coupled estrogen receptor (GPER) in melanogenesis. METHODS: GPER expression was detected in the A375 human melanoma cell line and B16 mouse melanoma cell line. Cell proliferation, melanin content, tyrosinase (TYR) activity, cyclic adenosine monophosphate (cAMP) level, and TYR and microphthalmia-related transcription factor (MITF) expression were measured. GPER activation was altered by agonist and antagonist treatment and its expression was downregulated by gene silencing. Estradiol-induced melanin synthesis and the activation of related signaling pathways were suppressed by inhibiting GPER via antagonist treatment. The relationship between GPER and TYR was evaluated in clinical chloasma samples by immunohistochemistry. RESULTS: Upregulation of GPER in A375 cells promoted melanogenesis, favored as indicated by increases in TYR and MITF expression and TYR activity. GPER activated melanin production via the cAMP-protein kinase (PK) A pathway, suggesting that GPER plays an important role in estrogen-induced melanin synthesis. The effect of GPER activation on cAMP-MITF-TYR signaling was also demonstrated in B16 cells. A significant association was observed between GPER and TYR expression in chloasma skin lesions relative to normal skin. CONCLUSION: GPER enhances melanin synthesis via cAMP-PKA-MITF-TYR signaling and modulates the effects of estrogen in melanogenesis. GPER is therefore a potential drug target for chloasma treatment. PMID- 27378492 TI - New developments in prenatal diagnosis of congenital adrenal hyperplasia. AB - Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is an autosomal recessive disorder caused by mutations in the CYP21A2 gene. Females affected with classical CAH are at risk for genital ambiguity, but can be treated in utero with dexamethasone before 9 gestational weeks to prevent virilization. Early genetic diagnosis is unavailable through current invasive methods of chorionic villus sampling and amniocentesis. New developments in prenatal genetic testing utilize fetal DNA extracted from maternal blood through noninvasive methods, which allow the determination of fetal gender and the diagnosis of CAH at an early gestational age (<9 weeks). Noninvasive prenatal diagnosis allows for the establishment of early and effective management plans in fetuses at risk for CAH and avoids unnecessary prenatal dexamethasone treatment. PMID- 27378493 TI - Becoming a "second victim" in health care: Pathway of recovery after adverse event. AB - INTRODUCTION: The healthcare worker involved in an unanticipated adverse patient event can become second victim. These workers suffer physically and psycho socially and try to overcome the post-event emotional stress by obtaining emotional support in a variety of ways. The goal of this research was to study second victims among health care providers in Italy. METHODS: This contribution contains the results of 33 interviews of nurses, physicians and other healthcare workers. After institutional approval, the semi-structured interview, composed of 25 questions, was translated from English into Italian. The audio-interviews were transcribed on paper verbatim by the interviewer. It was then verified if the interviewees experienced the six post-event stages of second victim recovery previously described within the literature. RESULTS: The interviewees described the post-event recovery stages described by literature but stages were not detailed in the exact succession order as the American study. All participants clearly remembered the adverse event and referred the physical and psycho-social symptoms. The psychological support obtained by second victims was described as poor and inefficient. DISCUSSION: The post-event recovery pathway is predictable but not always clearly respected as defined within this Italian sample. Future study of the second-victim phenomenon and desired supportive interventions is necessary to understand the experience and interventions to mitigate harm of future clinicians. Every day healthcare workers become second victims and, considering that human resources are the most important heritage of healthcare infrastructures, after an adverse event it is very important to execute valid interventional programs to support and train these workers. PMID- 27378494 TI - Star polymer synthesis vialambda-orthogonal photochemistry. AB - We introduce a light induced sequence enabling lambda-orthogonal star polymer formation via an arms-first approach, based on an alpha,omega-functional polymer carrying tetrazole and o-methyl benzaldehyde moieties, which upon irradiation can readily undergo cycloaddition with a trifunctional maleimide core. Depending on the wavelength, the telechelic strand can be attached to the core at either photo reactive end. PMID- 27378495 TI - Respiratory autoresuscitation following severe acute hypoxemia in anesthetized adult rats. AB - In the present study we investigated the pattern and efficacy of respiratory autoresuscitation in spontaneously breathing adult male rats across three separate anesthetic backgrounds. Each animal was administered one of three injectable anesthetics to achieve a surgical plane of anesthesia: ketamine xylazine (KET, n=10), pentobarbital (PEN, n=10), or urethane (URE, n=10). Animals were tracheostomized and equipped with a femoral artery catheter to record airflow and arterial pressures. In response to a bout of breathing anoxic air, none of the 10 URE animals were able to mount a successful autoresuscitation response. In contrast, all KET and PEN animals survived all four consecutive anoxic exposures, restoring eupneic breathing in all cases. Moreover, only 4/10 URE animals expressed gasping breaths following the onset of respiratory arrest, and these were temporally delayed (p<0.001) and much smaller in volume (P<=0.012) compared to KET and PEN animals. URE animals showed no clear aberrations in their cardiovascular responses to anoxia, with the exception of lower arterial pulse pressures compared to either KET or PEN animals at specific points following RA. Ketamine-xylazine and pentobarbital anesthesia can be reliably and effectively used to create models for the study of autoresuscitation in adult rats. In contrast, urethane causes catastrophic failure of respiratory autoresuscitation, by delaying or outright preventing the elaboration of gasping breaths following anoxia-induced respiratory arrest. The neuronal and synaptic alterations accompanying urethane anesthesia may therefore provide a means of understanding potential pathological alterations in rhythm generation that can predispose the respiratory control system to failed autoresuscitation following an episode of acute severe hypoxemia. PMID- 27378496 TI - Engineering E. coli for large-scale production - Strategies considering ATP expenses and transcriptional responses. AB - Microbial producers such as Escherichia coli are evolutionarily trained to adapt to changing substrate availabilities. Being exposed to large-scale production conditions, their complex, multilayered regulatory programs are frequently activated because they face changing substrate supply due to limited mixing. Here, we show that E. coli can adopt both short- and long-term strategies to withstand these stress conditions. Experiments in which glucose availability was changed over a short time scale were performed in a two-compartment bioreactor system. Quick metabolic responses were observed during the first 30s of glucose shortage, and after 70s, fundamental transcriptional programs were initiated. Since cells are fluctuating under simulated large-scale conditions, this scenario represents a continuous on/off switching of about 600 genes. Furthermore, the resulting ATP maintenance demands were increased by about 40-50%, allowing us to conclude that hyper-producing strains could become ATP-limited under large-scale production conditions. Based on the observed transcriptional patterns, we identified a number of candidate gene deletions that may reduce unwanted ATP losses. In summary, we present a theoretical framework that provides biological targets that could be used to engineer novel E. coli strains such that large scale performance equals laboratory-scale expectations. PMID- 27378498 TI - Welcome, thank you, and good luck! PMID- 27378497 TI - Thrombus-mimicking artifacts in two-point Dixon MRI: Prevalence, appearance, and severity. AB - PURPOSE: To evaluate the incidence and severity of potentially thrombus mimicking, flow-induced misallocation artifacts in a clinical setting. Two-point "Dixon" fat-water separation methods, with bipolar readout gradients, may suffer from flow-induced fat-water misallocation artifacts. If these artifacts occur within blood vessels, they may mimic thrombus. MATERIALS AND METHODS: Two-point Dixon coronal and axial images acquired in 102 consecutive patients were retrospectively evaluated for the presence of flow-induced artifacts in arteries and veins. Artifacts were graded on a 3-point scale (none, mild, severe) by two independent readers. Interreader agreement was evaluated with kappa statistics. RESULTS: Reader 1 reported 63 artifacts in 46 (45%) of the cases (severe in 19 cases, 18.6%). Reader 2 reported 51 artifacts in 43 (42.2%) of the cases (severe in 18 cases, 17.6%). Misallocation of fat and water was apparent in all datasets with severe artifacts, whereas variable signal intensity changes in water and fat images were observed in mild artifacts. Interreader agreement was good for artifacts appearing in coronal images (kappa = 0.7) and fair for artifact appearance in axial images (kappa = 0.24). CONCLUSION: Our study shows a high incidence of flow-induced mild and severe artifacts in a two-point Dixon method with bipolar readout gradients. This artifact should not be misinterpreted as intravascular thrombus. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:229 236. PMID- 27378499 TI - Push-pull flexibly-bridged bis(haloBODIPYs): solvent and spacer switchable red emission. AB - A series of uncommon bis(BODIPYs), involving a flexible bridge linking the BODIPY alpha-positions and key functionalities to efficiently give an electronic push pull effect, has been synthesized, as well as photophysically and structurally studied. It is demonstrated that the designed push-pull effect efficiently enables intramolecular charge transfer (ICT) processes upon photoexcitation, with the generated low-lying ICT state being the main deactivation channel from the locally excited state and, hence, ruling the fluorescence response. Noticeably, this response is modulated by the solvent polarity, and also by the bridge structure. Regarding this, BINOL- and BINAM-based bridges are found to promote an interesting unprecedented solvent-switchable dual emission from the ICT state with high Stokes shifts, triggering a significant bright red emission in less polar media. PMID- 27378500 TI - [An employer-based integrated approach to sickness absence]. PMID- 27378501 TI - [Quality and compliance with the regulations of workers'health examinations in relation to their preventive purpose]. AB - OBJECTIVE: To analyze whether examinations for health surveillance in Catalonia are carried out with a high enough degree of quality as to comply with the preventive aim of the regulations, and to identify potential differences by type of prevention service. METHOD: Qualitative and quantitative techniques. Body of data: Spanish regulations related to health surveillance, and a self-reported questionnaire answered by occupational health professionals who performed health examinations in their usual practice. Content analysis of regulations, identifying concepts, and linking them to survey questions. Quality criteria were established for each concept, referring to the minimum that must be met to ensure that the professional practice can be of quality; quality indicators (percentage of professionals whose practice met the quality criteria) were calculated globally and by type of prevention service; and quality standards (fulfilment of quality criteria by 75% or more of the professionals) were set. RESULTS: The concepts identified were: availability of clinical and exposure information, job specificity, identification of workers with special susceptibilities, referral to mutual insurance companies for appropriate diagnosis and treatment, development of preventive proposals, and professional independence and non detriment for workers. Quality indicators ranged between 0 and 88%. None of the concepts globally reached the quality standard. CONCLUSIONS: The quality of health examinations performed for health surveillance in Catalonia, doesn't seem to be high enough as to comply with the preventive aim of the regulations. The situation is worse in external prevention services. PMID- 27378502 TI - [Work-related violence among public health professionals (2008-2012)]. AB - OBJECTIVE: To describe the types of work-related violence and associated factors among professionals of the Navarra Health Service-Osasunbidea from August 2008 to December 2012. METHOD: This was a descriptive study of reported work-related violence incidents. The outcome variable was the type of violence (physical and/or verbal assault). The characteristics of the victims and the aggression were described using frequencies and percentages. Associations between the type of violence and the independent variables were evaluated using chi-square statistics. Work-related violence incidence rates per 100 worker-years were estimated and rates compared using the rate ratio. RESULTS: 684 attacks were reported (45.4%were verbal).Mental health was the service where most attacks were recorded (51.9%), predominantly physical. Verbal aggression were most common in primary and specialty care. The incidence of aggressions were highest among orderlies (4.5 per 100 worker-years), mental health (5,5 per 100 worker-years) and professionals under 35 years of age (5.9 per 100 worker-years). Rates were similar in men and women (1.6 per 100 workeryears). However, when stratified by professional category, women at the greatest risk were female physicians and administrative assistants; among the men, risk was greatest among male nurses and orderlies. CONCLUSIONS: Factors associated with work-related violence, such as location and professional category, should be considered when designing preventive measures. PMID- 27378503 TI - [Healthy university: a health promotion strategy and health for all policies for the creation of a healthy workplace]. AB - The objective of this study is to describe a model of healthy university and the experience of the International University of Catalonia in creating a healthy workplace. The model focuses on interventions and programs for changing the population distribution of the main risk factors for non-communicable diseases. The three pillars of the model are: a) interventions and programs, b) surveillance and evaluation, and c) education and research in health for all policies. The university as a place of work and knowledge-linked entity is an ideal institution for health promotion. The proposed model may be useful for incorporating the concept of health promotion into the university culture, and in its institutional policies and study plans. PMID- 27378506 TI - The Poet's Obligation (The Problem of a "Calling"). PMID- 27378504 TI - Three year functional changes and long-term mortality hazard in community dwelling older men. AB - BACKGROUND: Low levels of physical function have been associated with higher mortality hazard in older persons. However, few studies have investigated the association between functional changes and subsequent mortality. This study aimed to examine whether 3-year functional changes independently predict subsequent all cause mortality. METHODS: This population-based cohort study included 171 community-dwelling men aged >=71years at wave 2 (baseline of the present analysis), living in the semi-rural community of Merelbeke (Belgium). Physical function assessments included the Short Form-36 (SF-36) Physical Function Index, Grip strength, Chair rising, and Timed Up and Go. Changes over a 3-year time were calculated using data obtained at four annual visits. RESULTS: After a 15-year follow-up, 149 men (87%) died. Median survival time was 8.2 (4.2-12.4) years. Physical function assessed at a single time point (at wave 2 or wave 5) was significantly associated with subsequent mortality hazard, independently from future or preceding 3-year changes. Greater functional declines during the 3-year follow-up were associated with higher mortality hazards. These associations were 1) more pronounced within the first seven years, 2) independent from baseline age, polypharmacy, depression, disability, and physical function, and 3) no longer significant when closure physical function was taken into account. CONCLUSION: Physical function assessed at a single time point is a robust predictor of all-cause long-term mortality in community-dwelling older men. Yet, repeated assessments of physical function can provide prognostic information beyond that available from single initial assessment. However, with repeated assessments, most prognostic information can be found in the final assessment of physical function. PMID- 27378505 TI - Gallium, a promising candidate to disrupt the vicious cycle driving osteolytic metastases. AB - Bone metastases of breast cancer typically lead to a severe osteolysis due to an excessive osteoclastic activity. On the other hand, the semi-metallic element gallium (Ga) displays an inhibitory action on osteoclasts, and therefore on bone resorption, as well as antitumour properties. Thus, we explored in vitro Ga effects on osteoclastogenesis in an aggressive bone metastatic environment based on the culture of pre-osteoclast RAW 264.7 cells with conditioned medium from metastatic breast tumour cells, i.e. the breast tumour cell line model MDA-MB-231 and its bone-seeking clone MDA-231BO. We first observed that Ga dose-dependently inhibited the tumour cells-induced osteoclastic differentiation of RAW 264.7 cells. To mimic a more aggressive environment where pro-tumourigenic factors are released from bone matrix due to osteoclastic resorption, metastatic breast tumour cells were stimulated with TGF-beta, a mayor cytokine in bone metastasis vicious cycle. In these conditions, we observed that Ga still inhibited cancer cells-driven osteoclastogenesis. Lastly, we evidenced that Ga affected directly and strongly the proliferation/viability of both cancer cell lines, as well as the expression of major osteolytic factors in MDA-231BO cells. With the exception of two small scale clinical studies from 1980s, this is the first time that antitumour properties of Ga have been specifically studied in the context of bone metastases. Our data strongly suggest that, through its action against the vicious cycle involving bone cells and tumour cells, Ga represents a relevant and promising candidate for the local treatment of bone metastases in patients with breast cancer. PMID- 27378507 TI - Effects of standardized Ginkgo biloba extract on the acquisition, retrieval and extinction of conditioned suppression: Evidence that short-term memory and long term memory are differentially modulated. AB - Studies in our laboratory have characterized the putative neuromodulatory effects of a standardized extract of the green leaves of Ginkgo biloba (EGb), which comprises a formulation of 24% ginkgo-flavoglycosides and 6% ginkgo-terpenoid lactones, on conditioned suppression. This model comprises a suitable animal model for investigating the behavioral changes and pharmacological mechanisms that underlie fear memory and anxiety. The characterization of the effects on distinct stages of fear memory or fear extinction will help illustrate both the beneficial and harmful effects. Three hundred adult male Wistar rats were randomly assigned to 30 groups according to the treatment as follows: i-ii) control groups (CS-US and CSno-US); iii) vehicle group (12% Tween(r)80); and iv vi) EGb groups (250, 500 and 1000mgkg(-1)); or experimental procedures designed to assess the effects of EGb treatment prior to the acquisition (n=20 per group) and retrieval of conditioned fear (n=10 per group) or prior to the extinction training (n=10 per group) and extinction retention test (n=10 per group). Furthermore, to better understand the effects of acute EGb treatment on fear memory, we conducted two additional analyses: the acquisition of within- and between-session extinction of fear memory (short- and long-term memory, respectively). No difference was identified between the control and treatment groups during the retention test (P>0.05), with the exception of the CSno-US group in relation to all groups (P<0.05). A between-session analysis indicated that EGb at 250mgkg(-1) facilitated the acquisition of extinction fear memory, which was verified by the suppression ration in the first trial of extinction training (SR=0.39) and the extinction retention test session (SR=0.53, P<0.05), without impairments in fear memory acquisition, which were evaluated during the retention test (SR=0.79). Moreover, EGb administered at 1000mgkg(-1) prior to conditioning did not enhance the long-term extinction memory, i.e., it did not prevent the return of extinguished fear memory in the extinction retention test, in which the spontaneous recovery of fear was demonstrated (SR=0.63, P<0.05); however, it significantly facilitated short-term memory as verified by data from the within-session extinction (1 to 8-10 trials) during the retention test (SR=0.73 to SR=0.59; P<0.05) and the extinction retention test (SR=0.63 to SR=0.41; P<0.05). Moreover, spontaneous recovery was identified in response to a higher dose of EGb when administered prior to extinction training (SR=0.75, P<0.05) and the extinction retention test (SR=0.70; P<0.05). At dose of 500mgkg( 1) EGb reduced the suppression ratio when administered prior to the retention test (SR=0.57) and extinction training (SR=0.55; P<0.05) without preventing the acquisition of fear memory, which suggests that EGb has anti-anxiety effects. Taken together, the current findings suggest that EGb differentially modulates short- and long-term memory, as well as anxiety-like behavior. The actions of EGb may provide information regarding the beneficial effects in the prevention and treatment of neurocognitive impairments and anxiety disorders. Additional analyses are necessary to facilitate an understanding of these effects; however, previous data from our group suggest that GABAergic, serotoninergic and glutamatergic receptors are potential targets of the effects of EGb on conditioned suppression. PMID- 27378508 TI - Behavioural and neurophysiological disruption of corticobulbar motor systems and their effects on sequential pharyngeal swallowing. AB - Primary motor networks are known to be involved in the control of voluntary oral movements as well as the modulation of pharyngeal movements during experimentally controlled single swallows performed on command. The role of these networks in the more typical task of sequential swallowing remains unexplored. This study evaluated the hypothesis that experimental disruption of motor cortical activation would reduce the rate and regularity of repeatedly performed volitional or volitionally initiated motor tasks controlled by corticospinal (finger tapping) and corticobulbar (eyebrow movement, jaw opening, volitional sequential swallowing) motor systems, but would not influence a more reflexive corticobulbar task (reflexive sequential swallowing to pharyngeal water infusion). This premise was investigated in 24 healthy participants using two techniques: a dual task paradigm and a transcranial magnetic stimulation paradigm. Disruption effects were quantified by changes in rate and regularity of performance for each tested motor task. In summary, volitional motor tasks controlled by corticospinal motor networks (finger tapping) are more susceptible to behavioural and neurophysiological disruption than tasks controlled by cortiobulbar motor networks containing a reflexive component (both volitional and experimentally initiated consecutive swallowing). Purely volitional motor tasks controlled by the corticobulbar motor system (eyebrow raising or jaw opening) were affected in similar ways as the volitional corticospinal motor tasks. In summary, tasks involving sequential pharyngeal swallowing - whether volitionally or experimentally initiated - are largely robust against disruption of primary cortical motor networks, supporting a key role of medullary CPGs in the motor control of sequential pharyngeal swallowing. PMID- 27378509 TI - Olfactory attractants and parity affect prenatal androgens and territoriality of coyote breeding pairs. AB - Hormones are fundamental mediators of personality traits intimately linked with reproductive success. Hence, alterations to endocrine factors may dramatically affect individual behavior that has subsequent fitness consequences. Yet it is unclear how hormonal or behavioral traits change with environmental stressors or over multiple reproductive opportunities, particularly for biparental fauna. To simulate an environmental stressor, we exposed captive coyote (Canis latrans) pairs to novel coyote odor attractants (i.e. commercial scent lures) mid gestation to influence territorial behaviors, fecal glucocorticoid (FGMs) and fecal androgen metabolites (FAMs). In addition, we observed coyote pairs as first time and experienced breeders to assess the influence of parity on our measures. Treatment pairs received the odors four times over a 20-day period, while control pairs received water. Odor-treated pairs scent-marked (e.g. urinated, ground scratched) and investigated odors more frequently than control pairs, and had higher FAMs when odors were provided. Pairs had higher FAMs as first-time versus experienced breeders, indicating that parity also affected androgen production during gestation. Moreover, repeatability in scent-marking behaviors corresponded with FGMs and FAMs, implying that coyote territoriality during gestation is underpinned by individually-specific hormone profiles. Our results suggest coyote androgens during gestation are sensitive to conspecific olfactory stimuli and prior breeding experience. Consequently, fluctuations in social or other environmental stimuli as well as increasing parity may acutely affect coyote traits essential to reproductive success. PMID- 27378510 TI - Do physicians clean their hands? Insights from a covert observational study. AB - Physicians are notorious for poor hand hygiene (HH) compliance. We wondered if lower performance by physicians compared with other health professionals might reflect differences in the Hawthorne effect. We introduced covert HH observers to see if performance differences between physicians and nurses decreased and to gain further insights into physician HH behaviors. Following training and validation with a hospital HH auditor, 2 students covertly measured HH during clinical rotations. Students rotated off clinical services every week to increase exposure to different providers and minimize risk of exposing the covert observation. We compared covertly measured HH compliance with data from overt observation by hospital auditors during the same time period. Covert observation produced much lower HH compliance than recorded by hospital auditors during the same time period: 50.0% (799/1597) versus 83.7% (2769/3309) (P < 0.0002). The difference in physician compliance between hospital auditors and covert observers was 19.0% (73.2% vs 54.2%); for nurses this difference was much higher at 40.7% (85.8% vs 45.1%) (P < 0.0001). Physician trainees showed markedly better compliance when attending staff cleaned their hands compared with encounters when attending did not (79.5% vs 18.9%; P < 0.0002). Our study suggests that traditional HH audits not only overstate HH performance overall, but can lead to inaccurate inferences about performance by professional groupings due to relative differences in the Hawthorne effect. We suggest that future improvement efforts will rely on more accurate HH monitoring systems and strong attending physician leadership to set an example for trainees. Journal of Hospital Medicine 2015;11:862-864. (c) 2015 Society of Hospital Medicine. PMID- 27378511 TI - Is the image "right" for everyone? Introduction to the parallax effect in laparoscopic surgery. AB - AIM OF THE STUDY: During minimally invasive abdominal surgery, a laparoscope is used to film the procedure, which is transmitted to a flat screen monitor. The horizontality of the image depends on the orientation in space and the visual comfort of the surgeon. Observing the screen via a lateral angle of incidence frequently results in the camera assistant making errors in determining the horizontality of the image. Thus, what is "right" for the camera assistant is not necessarily 'right' for the surgeon. We aimed to explain the impact of these errors in laparoscope manipulation, by the description of the parallax effect. PATIENTS AND METHODS: To describe this phenomenon of perceptions changing depending on the angle of view, from the basis of the parallax effect, we observed the change of position and for two observers, (the surgeon and the camera assistant) seated at two different locations, using an experimental set up (i.e., photography equipment, a screen and a pelvitrainer). RESULTS: The position of the camera assistant positioned at an angle of incidence of 45 degrees from the surgeon, the observation of the screen with a lateral incidence changes the perception of the image viewed on the screen. For correcting the conflict between the subjective visual perception of the camera assistant and the actual image horizon, the camera assistant instinctively rotates the image, which can lead to an "incorrect" image, deleterious for the surgeon. CONCLUSIONS: This article introduces a previously unexplained concept in medical literature, called the parallax effect. The parallax effect results in the camera assistant making systematic errors in determining image horizontality on the screen. PMID- 27378512 TI - Thermal growth potential of Atlantic cod by the end of the 21st century. AB - Ocean warming may lead to smaller body sizes of marine ectotherms, because metabolic rates increase exponentially with temperature while the capacity of the cardiorespiratory system to match enhanced oxygen demands is limited. Here, we explore the impact of rising sea water temperatures on Atlantic cod (Gadus morhua), an economically important fish species. We focus on changes in the temperature-dependent growth potential by a transfer function model combining growth observations with climate model ensemble temperatures. Growth potential is expressed in terms of asymptotic body weight and depends on water temperature. We consider changes between the periods 1985-2004 and 2081-2100, assuming that future sea water temperatures will evolve according to climate projections for IPCC AR5 scenario RCP8.5. Our model projects a response of Atlantic cod to future warming, differentiated according to ocean regions, leading to increases of asymptotic weight in the Barents Sea, while weights are projected to decline at the southern margin of the biogeographic range. Southern spawning areas will disappear due to thermal limitation of spawning stages. These projections match the currently observed biogeographic shifts and the temperature- and oxygen dependent decline in routine aerobic scope at southern distribution limits. PMID- 27378513 TI - Allergy to local anesthetics: Reality or myth? AB - The incidence of allergic reactions to local anesthetics is low. Most cases involve a psychogenic reaction rather than an allergic reaction. Additives and preservatives added to local anesthetics may cause allergic reactions. Vascular resorption of epinephrine-containing local anesthetics may produce cardiovascular signs similar to an allergic reaction. Diagnosis of allergy to local anesthetics must be established by skin testing and provocative challenge. PMID- 27378514 TI - Ultrasensitive DNA detection based on two-step quantitative amplification on magnetic nanoparticles. AB - Sensitive detection of a specific deoxyribo nucleic acid (DNA) sequence is important for biomedical applications. In this report, a two-step amplification strategy is developed based on magnetic nanoparticles (MNPs) to achieve ultrasensitive DNA fluorescence detection. The first level amplification is obtained from multiple binding sites on MNPs to achieve thousands of probe DNA molecules on one nanoparticle surface. The second level amplification is gained by enzymatic reaction to achieve fluorescence signal enhancement. MNPs functionalized by probe DNA (DNAp) are bound to target DNA (t-DNA) molecules with a ratio of 1:1 on a substrate with capture DNA (DNAc). After the MNPs with DNAp are released from the substrate, alkaline phosphatase (AP) is labelled to MNPs via hybridization reaction between DNAp on MNPs and detection DNAs (DNAd) with AP. The AP on MNPs catalyses non-fluorescent 4-methylumbelliferyl phosphate (4 MUP) to fluorescent 4-methylumbelliferone (4-MU) with high intensity. Finally, fluorescence intensity of the 4-MU is detected by a conventional fluorescence spectrophotometer. With this two-step amplification strategy, the limit of detection (LOD) of 2.8 * 10(-18) mol l(-1) for t-DNA has been achieved. PMID- 27378516 TI - Rh(I) -Catalyzed Intramolecular Carbonylative C-H/C-I Coupling of 2-Iodobiphenyls Using Furfural as a Carbonyl Source. AB - Synthesis of fluoren-9-ones by a Rh-catalyzed intramolecular C-H/C-I carbonylative coupling of 2-iodobiphenyls using furfural as a carbonyl source is presented. The findings indicate that the rate-determining step is not a C-H bond cleavage but, rather, the oxidative addition of the C-I bond to a Rh(I) center. PMID- 27378515 TI - IL-10 differentially controls the infiltration of inflammatory macrophages and antigen-presenting cells during inflammation. AB - The inflammatory activation and recruitment of defined myeloid populations is essential for controlling the bridge between innate and adaptive immunity and shaping the immune response to microbial challenge. However, these cells exhibit significant functional heterogeneity and the inflammatory signals that differentially influence their effector characteristics are poorly characterized. In this study, we defined the phenotype of discrete subsets of effective antigen presenting cells (APCs) in the peritoneal cavity during peritonitis. When the functional properties of these cells were compared to inflammatory monocyte derived macrophages we noted differential responses to the immune-modulatory cytokine IL-10. In contrast to the suppressive actions of IL-10 on inflammatory macrophages, the recruitment of APCs was relatively refractory and we found no evidence for selective inhibition of APC differentiation. This differential response of myeloid cell subsets to IL-10 may thus have limited impact on development of potentially tissue-damaging adaptive immune responses, while restricting the magnitude of the inflammatory response. These findings may have clinical relevance in the context of peritoneal dialysis patients, where recurrent infections are associated with immune-mediated membrane dysfunction, treatment failure, and increased morbidity. PMID- 27378517 TI - In-vivo absorption of pinocembrin-7-O-beta-D-glucoside in rats and its in-vitro biotransformation. AB - Pinocembrin-7-O-beta-D-glucoside (PCBG), a flavonoid isolated from Penthorum chinense Pursh., has significant liver-protecting effects. The pharmacokinetics of PCBG and its major metabolite pinocembrin (PCB) in rats were investigated in this study. A sensitive and accurate UPLC-MS/MS method was developed and validated for the simultaneous quantitative determination of PCBG and PCB in rat plasma after oral and intravenous administration of PCBG. After intravenous administration, PCBG was the main form in plasma. In contrast, after oral administration, the concentration of PCB was about 4-fold higher than that of PCBG, indicating that PCBG was metabolized to PCB. We also investigated the biotransformation of PCBG in vitro in order to understand whether the pH and the intestinal flora of gastrointestinal tract could affect the metabolism of PCBG. PCBG was incubated in rat plasma, liver homogenization, gastrointestial contents, liver microsomes (RLM) and hepatocytes in vitro. The data showed that PCB was quickly formed in the gastrointestinal incubation but PCBG was converted to PCB gradually in other incubations. The results indicated that the majority of PCBG was converted to its aglycone PCB in digestive system after oral administration, and PCB could be the active ingredient in the body. PMID- 27378518 TI - Correlation of multiparameter flow cytometry and bone marrow trephine immunohistochemistry in the identification and characterization of neoplastic plasma cells. PMID- 27378520 TI - Non-traumatic vertebral artery dissection presenting with unilateral cervical pain, hemilateral vision problems and headache. AB - Spontaneous vertebral artery dissection is a rare condition, mainly affecting young adults with non-specific symptoms, which are often considered not severe. We report a case of a non-traumatic vertebral artery dissection in a 30-year-old woman. Our patient presented with unilateral right-sided neck pain and frontal headache during 3 weeks and recently developed right-sided vision problems. History and clinical findings were non-specific. Neurovascular imaging showed a right-sided vertebral artery dissection from C2 to C6 with an intima flap at C5 C6. The patient was observed in the stroke unit for 1 week and antithrombotics were given during 3 months. There was a complete revascularization of the vertebral artery after 3 months. A review of literature is given concerning predisposing factors, clinical symptoms, neurovascular imaging and treatment options. PMID- 27378519 TI - Beef palatability and its relationship with protein degradation and muscle fibre type profile in longissimus thoracis in Alentejana breed from divergent growth pathways. AB - The traditional beef production in the South of Portugal is based on a discontinuous growth (DG) system that requires lower external inputs and could enhance meat quality and financial returns to cattle producers. This system allows farmers to take advantage of the bull's compensatory growth when the pasture is abundant and finishes the cattle on concentrates for 2 to 3 months before slaughter. The fast gain rate before slaughter could be a valuable strategy to improve tenderness and to reduce its inconsistency in beef production. Therefore, the aim of this study was to evaluate the effects of production system (continuous growth (CG) v. DG) on longissimus thoracis muscle properties from Alentejana bulls. In total, 40 Alentejana male calves were allocated to two distinct feeding regimes: in the CG system, animals were fed concentrate plus hay and slaughtered at 18 months of age, whereas in the DG system, animals were fed on hay until 15 months of age and then fed the same diet provided to the CG group until 24 months of age. The DG system had a positive impact on meat tenderness (P<0.001) and global acceptability (P<0.001). DG bulls had greater fibre cross-sectional area (CSA) of glycolytic fibres (P<0.05) and relative area of the muscle (RA) occupied by type IIX fibres (P<0.01) and greater levels of alpha-actinin (P<0.05) and myosin light chain 2 (P<0.01) proteins, and pH24h (P<0.01) than CG bulls. The latter had greater CSA of type I (P<0.05) and type IIA (P<0.01) and greater RA of type IIA (P<0.05) and oxidative (P<0.05) than CG bulls. The compensatory growth production system had a positive impact on meat tenderness and global acceptability, overcoming the negative effects of slaughter of the bulls at a later age. The DG beef system could be a worthwhile strategy of beef production in Mediterranean areas due to the low-quality pasture in summer. PMID- 27378521 TI - Fifteen-minute consultation: public health for paediatricians-adolescent public health. AB - Paediatricians have a key role to play in ensuring a holistic, integrated approach is taken to meeting adolescent health needs. There is increasing evidence that failure to do so can lead to poor healthcare experience, avoidable ill health and increased need for healthcare services, both in the short term and in adult life. This article aims to guide paediatricians in answering the questions 'How well are the public health and clinical needs of the adolescent population in my area being met? And how can we improve?' PMID- 27378522 TI - Choroidal melanoma treated with stereotactic fractionated radiotherapy and prophylactic intravitreal bevacizumab: The Dunedin Hospital experience. AB - INTRODUCTION: Choroidal melanoma (CM) is the most common primary ocular malignancy in adults. This study reviewed the Dunedin Hospital (DH) experience in the treatment of CM with stereotactic fractionated radiotherapy (SRT) and the outcome of prophylactic use of intravitreal injection bevacizumab (PIB) in preventing radiation retinopathy (RR). METHODS: A retrospective study was conducted of patients at DH who underwent SRT for CM with and without PIB from 1 January 2001 to 31 January 2012. In DH, some patients who had SRT following the introduction of intravitreal bevacizumab in December 2006 were also treated with PIB with the expectation that this might reduce the risk of developing RR, although the evidence of its effectiveness in this respect is not clear. The primary outcome measure was local progression as monitored with regular ultrasound. Secondary outcome measures were metastatic progression incidence, enucleation incidence, no functional vision incidence, overall survival, disease specific mortality, incidence of RR, and radiotherapy to clinical diagnosis of RR time. RESULTS: Twenty-seven patients who were followed up at DH were reviewed after a mean follow-up of 5.1 years (range 0.4-12.6). Fourteen patients received PIB. The local progression, metastatic progression and enucleation rate were 4%, 8% and 11%, respectively. The no functional vision (hand movements or less) rate was 62%. Overall survival was 63%, but only three (11%) deaths were due to metastatic choroidal melanoma. Incidence of RR was 57% and 54% for those that received PIB and those who did not, respectively. PIB did not reduce the rate of RR (P = 1.00). CONCLUSION: This study reaffirmed that SRT achieves very good local control and eye retention rates. PIB did not appear to reduce the radiation retinopathy rate in this study, and more studies are required especially Phase II and III trials to determine PIB efficacy in preventing RR. PMID- 27378524 TI - Stellate Ganglion Block for Debilitating Photophobia Secondary to Trigeminal, Postherpetic Neuralgia. AB - OBJECTIVES: The primary objective of this case report was to demonstrate the therapeutic benefit of stellate ganglion block in trigeminal postherpetic neuralgia. METHODS: This was a case report on a single patient who presented with debilitating photophobia secondary to left-sided trigeminal postherpetic neuralgia. A left-sided stellate ganglion block was performed on the patient under fluoroscopic guidance. The primary endpoints were VAS pain scores and changes in functional capacity. RESULTS: The patient demonstrated significant reduction in her VAS pain score and improved functional capacity for approximately 6 months after the intervention. This case report provides evidence that sympathectomy via a stellate ganglion block can treat photophobia secondary to postherpetic neuralgia in the V1 distribution. PMID- 27378523 TI - Multiple CDK inhibitor dinaciclib suppresses neuroblastoma growth via inhibiting CDK2 and CDK9 activity. AB - Neuroblastoma (NB), the most common extracranial solid tumor of childhood, is responsible for approximately 15% of cancer-related mortality in children. Aberrant activation of cyclin-dependent kinases (CDKs) has been shown to contribute to tumor cell progression in many cancers including NB. Therefore, small molecule inhibitors of CDKs comprise a strategic option in cancer therapy. Here we show that a novel multiple-CDK inhibitor, dinaciclib (SCH727965, MK 7965), exhibits potent anti-proliferative effects on a panel of NB cell lines by blocking the activity of CDK2 and CDK9. Dinaciclib also significantly sensitized NB cell lines to the treatment of chemotherapeutic agents such as doxorubicin (Dox) and etoposide (VP-16). Furthermore, dinaciclib revealed in vivo antitumor efficacy in an orthotopic xenograft mouse model of two NB cell lines and blocked tumor development in the TH-MYCN transgenic NB mouse model. Taken together, this study suggests that CDK2 and CDK9 are potential therapeutic targets in NB and that abrogating CDK2 and CDK9 activity by small molecules like dinaciclib is a promising strategy and a treatment option for NB patients. PMID- 27378525 TI - Maternal fatty acid intake during pregnancy and the development of childhood overweight: a birth cohort study. AB - BACKGROUND: Maternal diet during pregnancy may contribute to the risk of offspring adiposity. OBJECTIVES: The objective of the study is to explore the associations between maternal antenatal dietary fatty acid intake and the risk of offspring overweight and obesity at the ages of 2 to 7 years. METHODS: In a prospective Finnish birth cohort with 3807 mother-child pairs, maternal diet in late pregnancy was assessed with a food frequency questionnaire. Intakes of total fatty acids and individual saturated, monounsaturated and polyunsaturated fatty acids (PUFAs) were calculated. Generalized estimating equation models were used to study the associations of maternal dietary variables with repeatedly measured offspring overweight and obesity. RESULTS: In girls, maternal intake ratio of n 6:n-3 PUFAs had a U-shaped association with obesity (adjusted OR for the lowest 2.0 [95% CI 1.27-3.20] and the highest 1.7 [1.03-2.73] vs. the two middle quartiles of n-6:n-3 PUFAs, p = 0.01). In boys, arachidonic acid (20:4n-6): docosahexaenoic acid + eicosapentaenoic acid ratio was associated with obesity (adjusted OR for the lowest 1.0 [0.60-1.57] and the highest 0.5 [0.26-0.88] vs. the two middle quartiles, p = 0.02). Saturated fatty acids and monounsaturated fatty acids were not associated with overweight or obesity in either sex. CONCLUSIONS: Maternal intakes of PUFAs in late pregnancy were associated with risk of later obesity differently in girls and boys. PMID- 27378526 TI - Commentary: A Humanized Clinically Calibrated Quantitative Systems Pharmacology Model for Hypokinetic Motor Symptoms in Parkinson's Disease. PMID- 27378527 TI - Effects of Theophylline with Methylprednisolone Combination Therapy on Biomechanics and Histopathology in Diaphragm Muscles of Rats. AB - The purpose of this study was to investigate the effects of theophylline and methylprednisolone on the mechanical response and histopathology of hemidiaphragm muscle in rats. In the current study, we aimed to investigate the effects of theophylline and methylprednisolone, which are frequently used in clinics and which have different effects on the respiratory system and on the biomechanics and histopathology of the diaphragm muscle. The study included four groups of rats. Group T received 1 mg/kg of intraperitoneal theophylline, group M received 2 mg/kg of intraperitoneal methylprednisolone, group TM received 1 mg/kg of intraperitoneal theophylline plus 2 mg/kg of intraperitoneal methylprednisolone, and group K received of 1 mL intraperitoneal isotonic solution (of 0.9 % NaCl). The medications were continued for 7 days in each group. The rats underwent cervical dislocation under anesthesia on the eighth day, and their diaphragm samples were extracted. The left hemidiaphragm was used for the investigation of biomechanical parameters, and the right hemidiaphragm was used for the histopathological evaluation. It was observed that the medication administered in group T increased the contraction strength and duration compared with that in group M. Additionally, the duration of semi-relaxation was prolonged in group T compared with group M. The highest contraction strength and the longest contraction period among all of the groups were observed in group TM. It was concluded that the combined use of theophylline and methylprednisolone had positive effects on the contraction strength and the durations of contraction and semi-relaxation of the diaphragm muscle. In addition, both drugs had synergistic effects on each other. PMID- 27378528 TI - Hesperidin Alleviates Lipopolysaccharide-Induced Neuroinflammation in Mice by Promoting the miRNA-132 Pathway. AB - Previous studies have demonstrated that hesperidin, a flavanone glycoside from citrus fruits, produces antidepressant-like effects in both mice and rats. However, whether these effects are mediated by pro-inflammatory cytokines remains unknown. In the present study, we attempted to investigate the effects of hesperidin on the depressive-like behavior; the serum corticosterone concentrations; and the interleukin (IL)-1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) levels in lipopolysaccharide (LPS)-induced depression-like mice. In particular, we evaluated the miRNA-132 expression after LPS and hesperidin treatment. We found that LPS injection not only decreased the sucrose preference and increased the serum corticosterone levels but also elevated IL 1beta, IL-6, and TNF-alpha in the prefrontal cortex. More importantly, LPS down regulated the expression of miRNA-132. Pre-treatment with hesperidin (25, 50, 100 mg/kg) for 7 days prevented these abnormalities induced by LPS injection. In contrast, this effect of hesperidin was abolished by a miRNA-132 antagomir. Taken together, these results suggest that the antidepressant-like mechanisms of hesperidin are at least partially related to decreased pro-inflammatory cytokine levels via the miRNA-132 pathway in the brain. PMID- 27378530 TI - [A painful knee]. PMID- 27378531 TI - [Bridging anticoagulation in patients with atrial fibrillation: Is it mandatory ?] PMID- 27378529 TI - Melatonin Alters the Mechanical and Thermal Hyperalgesia Induced by Orofacial Pain Model in Rats. AB - Melatonin is a neuroendocrine hormone that presents a wide range of physiological functions including regulating circadian rhythms and sleep, enhancing immune function, sleep improvement, and antioxidant effects. In addition, melatonin has received special attention in pain treatment since it is effective and presents few adverse effects. In this study, we evaluated the effect of acute dose of melatonin upon hyperalgesia induced by complete Freund's adjuvant in a chronic orofacial pain model in Sprague-Dawley rats. Nociceptive behavior was assessed by facial Von Frey and the hot plate tests at baseline and thereafter 30, 60, and 120 min, 24 h, and 7 days after melatonin treatment. We demonstrated that acute melatonin administration alters mechanical and thermal hyperalgesia induced by an orofacial pain model (TMD), highlighting that the melatonin effect upon mechanical hyperalgesia remained until 7 days after its administration. Besides, we observed specific tissue profiles of neuroimmunomodulators linked to pain conditions and/or melatonin effect (brain-derived neurotrophic factor, nerve growth factor, and interleukins 6 and 10) in the brainstem levels, and its effects were state-dependent of the baseline of these animals. PMID- 27378532 TI - Purification and characterisation of a salt-stable protease from the halophilic archaeon Halogranum rubrum. AB - BACKGROUND: Because proteases play an important role in the fermentation of fish sauce, the purification and characterisation of an extracellular protease from the halophilic archaeon Halogranum rubrum was investigated. RESULTS: The molecular mass of the protease was estimated to be approximately 47 kDa based on sodium dodecyl sulfate-polyacrylamide gel electropheresis (SDS-PAGE) and native PAGE analysis. The optimum conditions for catalytic activity were pH 8.0 and 50 degrees C. The protease showed alkaline stability (pH 7.0-10.0). The protease also exhibited novel catalytic ability over a broad range of salinity (NaCl 0-3 mol L-1 ). Calcium ion enhanced the proteolytic activity of the enzyme. The Km and Vmax values of the purified protease for casein were calculated to be 4.89 mg mL-1 and 1111.11 U mL-1 , respectively. The protease was strongly inhibited by ethylenediamine tetraacetic acid (EDTA) and phenylmethanesulfonyl fluoride (PMSF). Meanwhile, the protease was stable in the presence of Triton X-100, isopropanol, ethanol or dithio-bis-nitrobenzoic (DTNB), but was inhibited by sodium dodecyl sulfate (SDS), dimethyl sulfoxide (DMSO) or methanol. MALDI TOF/TOF MS analysis revealed that the protease shared some functional traits with protease produced by Halogranum salarium. Furthermore, it exhibited high hydrolytic activity on silver carp myosin protein. CONCLUSION: The protease is an alkaline and salt-tolerant enzyme that hydrolyses silver carp myosin with high efficiency. These excellent characteristics make this protease an attractive candidate for industrial use in low-salt fish sauce fermentation. (c) 2016 Society of Chemical Industry. PMID- 27378533 TI - Context Effects in Forensic Entomology and Use of Sequential Unmasking in Casework. AB - Context effects are pervasive in forensic science, and are being recognized by a growing number of disciplines as a threat to objectivity. Cognitive processes can be affected by extraneous context information, and many proactive scientists are therefore introducing context-minimizing systems into their laboratories. Forensic entomologists are also subject to context effects, both in the processes they undertake (e.g., evidence collection) and decisions they make (e.g., whether an invertebrate taxon is found in a certain geographic area). We stratify the risk of bias into low, medium, and high for the decisions and processes undertaken by forensic entomologists, and propose that knowledge of the time the deceased was last seen alive is the most potentially biasing piece of information for forensic entomologists. Sequential unmasking is identified as the best system for minimizing context information, illustrated with the results of a casework trial (n = 19) using this approach in Victoria, Australia. PMID- 27378534 TI - [Usefulness of a rapid intrapartum real-time PCR assay in comparison with the group B Streptococcus culture screening at the end of pregnancy in pregnant women]. AB - OBJECTIVES: The objectives were to evaluate and compare the diagnostic accuracy of a rapid real-time PCR assay at the onset of labor with those of the current antenatal culture-based test at 34-38 weeks gestation for group B Streptococcus (GBS) screening. MATERIALS AND METHODS: A prospective study including all pregnant women admitted for delivery after a 34-week gestation period was conducted in October 2012 at the Grenoble University Hospital Centre. A first culture-based GBS screening test was performed between 34 and 38 weeks of gestation followed by a second screening test at the onset of labor, using a real time PCR Assay and a culture-based method (gold standard) in order to calculate the diagnostic accuracy. RESULTS: One hundred an fifty-seven patients were enrolled. The sensitivity was 94.4% (95% CI, 72.7-99.9%) with intrapartum PCR assay and 50% (95% CI, 26-74%) with antepartum culture. Prevalence of GBS colonization was 7.6% with the antepartum culture method, 11.5% with intrapartum culture and 16.6% by using PCR-test. CONCLUSION: Intrapartum PCR shows a much higher sensitivity compared to the antepartum culture-based screening mainly due to variations in GBS colonization and could allow us to target patients requiring intrapartum antibiotic prophylaxis more effectively. PMID- 27378535 TI - The photobase generator nifedipine as a novel matrix for the detection of polyphenols in matrix-assisted laser desorption/ionization mass spectrometry. AB - Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) is widely used for the detection and analysis of ionizable compounds. However, the method has less potential for the analysis of neutral compounds, such as polyphenols, owing to their lack of favorable proton-attachment or -removal groups. In this study, we reported for the first time that nifedipine (2,6 dimethyl-3,5-dicarbomethoxy-4-(2-nitrophenyl)-1,4-dihydropyridine), which is a strong photobase generator commonly used in polymerization, can abstract protons from neutral compounds in negative mode-MALDI experiments. When nifedipine (5 mg/ml) was used as a matrix reagent, the limit of detection (LOD) for epigallocatechin-3-O-gallate (EGCG) was determined to be 100 fmol/spot, which constitutes >50-fold improvement compared to the LOD obtained when trans-3 indoleacrylic acid, a matrix reagent previously reported for polyphenol detection, was used. Of the dihydropyridines investigated, only nifedipine facilitated the detection of EGCG, suggesting that the nitrosophenyl pyridine derivative of nifedipine formed by photoreduction under laser irradiation at 355 nm plays a crucial role in detecting polyphenols in negative mode. Reduced MS detection of 5-O-methylnaringenin indicated that nifedipine may preferably remove a proton from the 5-position OH group in the A ring of the flavonoid skeleton. The significant MS detection by nifedipine was extensively observed for polyphenols including flavones, flavonones, chalcones, stilbenoids and phenolic acids. In conclusion, nifedipine can act as a novel matrix for improving polyphenol detection by MALDI-MS in negative mode. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27378536 TI - Successful factors to prevent pressure ulcers - an interview study. AB - AIMS AND OBJECTIVES: To explore successful factors to prevent pressure ulcers in hospital settings. BACKGROUND: Pressure ulcer prevalence has been recognised as a quality indicator for both patient safety and quality of care in hospital and community settings. Most pressure ulcer can be prevented if effective measures are implemented and evaluated. The Swedish Association of Local Authorities and Regions initiated nationwide pressure ulcer prevalence studies in 2011. In 2014, after four years of measurement, the prevalence was still unacceptably high on a national level. The mean prevalence of pressure ulcer in the spring of 2014 was 14% in hospital settings with a range from 2.7-36.4%. DESIGN: Qualitative semistructured interviews were conducted. METHODS: A qualitative content analysis, in addition to Promoting Action on Research Implementation in Health Services frameworks, was used in the analysis of the data text. Individual interviews and focus groups were used to create opportunities for both individual responses and group interactions. The study was conducted at six hospitals during the fall of 2014. RESULTS: Three main categories were identified as successful factors to prevent pressure ulcer in hospitals: creating a good organisation, maintaining persistent awareness and realising the benefits for patients. CONCLUSION: The goal for all healthcare personnel must be delivering high quality, sustainable care to patients. Prevention of pressure ulcer is crucial in this work. It seems to be easier for small hospitals (with a low number of units/beds) to develop and sustain an effective organisation in prevention work. RELEVANCE TO CLINICAL PRACTICE: The nurse managers' attitude and engagement are crucial to enable the personnel to work actively with pressure ulcer prevention. Strategies are proposed to advance clinical leadership, knowledge, skills and abilities for the crucial implementation of pressure ulcer prevention. PMID- 27378537 TI - Oscillatory profiles of positive, negative and neutral feedback stimuli during adaptive decision making. AB - The electrophysiological response to positive and negative feedback during reinforcement learning has been well documented over the past two decades, yet, little is known about the neural response to uninformative events that often follow our actions. To address this issue, we recorded the electroencephalograph (EEG) during a time-estimation task using both informative (positive and negative) and uninformative (neutral) feedback. In the time-frequency domain, uninformative feedback elicited significantly less induced beta-gamma activity than informative feedback. This result suggests that beta-gamma activity is particularly sensitive to feedback that can guide behavioral adjustments, consistent with other work. In contrast, neither theta nor delta activity were sensitive to the difference between negative and neutral feedback, though both frequencies discriminated between positive, and non-positive (neutral or negative) feedback. Interestingly, in the time domain, we observed a linear relationship in the amplitude of the feedback-related negativity (neutral>negative>positive), a component of the event-related brain potential thought to index a specific kind of reinforcement learning signal called a reward prediction error. Taken together, these results suggest that the reinforcement learning system treats neutral feedback as a special case, providing valuable information about the electrophysiological measures used to index the cognitive function of frontal midline cortex. PMID- 27378539 TI - Generalized colloidal synthesis of high-quality, two-dimensional cesium lead halide perovskite nanosheets and their applications in photodetectors. AB - All-inorganic cesium lead halide perovskite (CsPbX3, X = Cl, Br, and I) nanocrystals (NCs) are emerging as an important class of semiconductor materials with superior photophysical properties and wide potential applications in optoelectronic devices. So far, only a few studies have been conducted to control the shape and geometry of CsPbX3 NCs. Here we report a general approach to directly synthesize two-dimensional (2D) CsPbX3 perovskite and mixed perovskite nanosheets with uniform and ultrathin thicknesses down to a few monolayers. The key to the high-yield synthesis of perovskite nanosheets is the development of a new Cs-oleate precursor. The as-synthesized CsPbX3 nanosheets exhibit bright photoluminescence with broad wavelength tunability by composition modulation. The excellent optoelectronic properties of CsPbX3 nanosheets combined with their unique 2D geometry and large lateral dimensions make them ideal building blocks for building functional devices. To demonstrate their potential applications in optoelectronics, photodetectors based on CsPbBr3 nanosheets are fabricated, which exhibit high on/off ratios with a fast response time. PMID- 27378538 TI - Meta-analysis and psychophysiology: A tutorial using depression and action monitoring event-related potentials. AB - Meta-analyses are regularly used to quantitatively integrate the findings of a field, assess the consistency of an effect and make decisions based on extant research. The current article presents an overview and step-by-step tutorial of meta-analysis aimed at psychophysiological researchers. We also describe best practices and steps that researchers can take to facilitate future meta-analysis in their sub-discipline. Lastly, we illustrate each of the steps by presenting a novel meta-analysis on the relationship between depression and action-monitoring event-related potentials - the error-related negativity (ERN) and the feedback negativity (FN). This meta-analysis found that the literature on depression and the ERN is contaminated by publication bias. With respect to the FN, the meta analysis found that depression does predict the magnitude of the FN; however, this effect was dependent on the type of task used by the study. PMID- 27378540 TI - Providing Higher Value Care Through Population Health Management: What Is the Radiologist's Role? PMID- 27378541 TI - True Grit. PMID- 27378542 TI - Osteonecrosis of the Hip? PMID- 27378543 TI - Authors' Reply. PMID- 27378544 TI - Drowning among the lakeside fishing communities in Uganda: results of a community survey. AB - The study aimed to determine the drowning burden in four Ugandan lakeside districts; the prevalence of life jacket use, and community knowledge and attitudes regarding water safety. Subjects were recruited as they disembarked from boats. A structured questionnaire was used for demographics, experience on water, details of incidents in water, and awareness of drowning prevention measures. Focus group discussions (FGDs) and key informant interviews were held. The study interviewed 544 participants; 81.1% male, 86.8% below 45 years, and 51.1% involved in the fishing industry. A quarter (26.1%) of the respondents were observed wearing life jackets as they disembarked. Participants who had been in a boat that nearly capsized (57.8%), or that actually capsized (21.7%), were no more likely to wear life jackets than those who had not had these experiences. Three quarters (73.2%) did not know how to call for rescue, and only 48.7% could swim. There drowning fatality rate in this community was 502 deaths per 100,000 population. Majority of drowning events occurred during transportation (51.7%) or fishing (39.0%). The most frequently mentioned factors were stormy weather and overloading. Drowning is a common threat to young adults in the fishing communities around Lake Victoria. Few preventive interventions are in place. PMID- 27378545 TI - The effect of parental presence on the child's perception and co-operation during dental treatment. AB - AIM: This was to study the influence of parental presence during dental treatment on children's behaviour and perception. METHODS: Parents of 100 patients (mean age 7 +/- 2.2 years) who visited the Postgraduate Paediatric Dental Clinic were randomly divided into two equal groups during one familiarisation and two treatment sessions: (1) parent present in the surgery/operatory and (2) parent absent (with their child observed through a window). Both an independent paediatric dentist and the parent rated the child's behaviour using the Venham scale. The child's perception was measured using the Wong-Baker Faces Rating Scale (FPRS) at the end of every session. Statistical analysis was performed with the IBM Statistics SPSS 22.0 (p < 0.05). Comparisons between variables were performed with the Mann-Whitney U, Wilcoxon and Friedman's tests. RESULTS: According to the paediatric dentist's rating, children's behaviour was worse when the parent was absent, with a significant difference only for the second restorative treatment session (p = 0.011). There was no difference on parents' rating child behaviour scores between the two groups. There was no difference of children's own perception between the two groups, except for any increased discomfort found at the second treatment (p = 0.021) when the parent was present. In both groups, the dentist rated lower Venham scores (better child behaviour), than parents did (presence: p = 0.001, absence: p = 0.038). Children recorded worse scores than both parents and the paediatric dentist. CONCLUSION: The only significant finding lay in the antithesis of how children perceived their last treatment session and how the dentist rated children's behaviour regarding parental presence. Parents' scores of their child's behaviour were unrelated to parental presence. PMID- 27378546 TI - A Functional Taxonomy of Bottom-Up Sensory Feedback Processing for Motor Actions. AB - Humans are adept at performing an extraordinary breadth of voluntary motor actions that allow us to rapidly move around and interact with the environment. While voluntary motor actions necessarily include top-down intention to generate a motor act, a key to voluntary control is the selective use of bottom-up sensory feedback to select and guide motor actions. This review classifies the many ways in which sensory feedback is used by the motor system and highlights regularities in the timing of each class of motor responses to sensory stimuli, revealing a functional hierarchical organization of motor control. The highly automatic way in which feedback is typically used in goal-directed action blurs the distinction between reflexes and voluntary control. PMID- 27378547 TI - Do Cortical Circuits Need Protecting from Themselves? AB - All hippocampal and neocortical networks can be driven to seize quite easily. This can be done using drugs, by altering the ionic constituency of the bathing medium [cerebrospinal fluid (CSF)], or by electrical stimulation (both experimentally and clinically, as in electroconvulsive therapy). It is worth asking why this is so, because this will both tell us more about potentially devastating neurological disorders and extend our understanding of cortical function and architecture. Here I review work examining the features of cortical networks that bias activity towards and away from hyperexcitability. I suggest that several cellular- and circuit-level features of rapidly responsive interneuron networks tip the balance away from seizure in the healthy brain. PMID- 27378549 TI - Identification of learning-induced changes in protein networks in the hippocampi of a mouse model of Alzheimer's disease. AB - Memory loss is the most profound clinical manifestation in Alzheimer's disease (AD); however, the molecular mechanisms underlying these deficits are poorly understood. Identification of the molecular pathways involved in the onset of cognitive deficits may lead to the identification of key events in the pathogenesis of AD. Using isobaric tags for relative and absolute quantitation (iTRAQ) and proteomic methods, here we identified learning-induced changes in the hippocampal proteome of non-transgenic (NonTg) and 3 * Tg-AD mice, a widely used animal model of AD. We found that expression of 192 proteins was differentially regulated by learning in NonTg mice. Notably, of these 192 proteins, only 28 were also differentially regulated by learning in 3 * Tg-AD mice, whereas the levels of 164 proteins were uniquely changed in NonTg mice but not in 3 * Tg-AD mice. These data suggest that during learning, 3 * Tg-AD mice fail to differentially regulate 164 proteins. Gene ontology and protein interaction analyses indicated that these proteins were overrepresented in RNA processing, specifically RNA transport, splicing and mRNA translation initiation pathways. These findings suggest that mRNA-processing events that take place during learning and memory are significantly altered in 3 * Tg-AD mice. PMID- 27378548 TI - Methylation of the leukocyte glucocorticoid receptor gene promoter in adults: associations with early adversity and depressive, anxiety and substance-use disorders. AB - Early adversity increases risk for developing psychopathology. Epigenetic modification of stress reactivity genes is a likely mechanism contributing to this risk. The glucocorticoid receptor (GR) gene is of particular interest because of the regulatory role of the GR in hypothalamic-pituitary-adrenal (HPA) axis function. Mounting evidence suggests that early adversity is associated with GR promoter methylation and gene expression. Few studies have examined links between GR promoter methylation and psychopathology, and findings to date have been mixed. Healthy adult participants (N=340) who were free of psychotropic medications reported on their childhood experiences of maltreatment and parental death and desertion. Lifetime depressive and anxiety disorders and past substance use disorders were assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Methylation of exon 1F of the GR gene (NR3C1) was examined in leukocyte DNA via pyrosequencing. On a separate day, a subset of the participants (n=231) completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Childhood adversity and a history of past substance-use disorder and current or past depressive or anxiety disorders were associated with lower levels of NR3C1 promoter methylation across the region as a whole and at individual CpG sites (P<0.05). The number of adversities was negatively associated with NR3C1 methylation in participants with no lifetime disorder (P=0.018), but not in those with a lifetime disorder. GR promoter methylation was linked to altered cortisol responses to the Dex/CRH test (P<0.05). This study presents evidence of reduced methylation of NR3C1 in association with childhood maltreatment and depressive, anxiety and substance-use disorders in adults. This finding stands in contrast to our prior work, but is consistent with emerging findings, suggesting complexity in the regulation of this gene. PMID- 27378551 TI - Analysis of the complete genome sequence of black queen cell virus JL1 from infected honeybees in China. AB - There are six strains of the complete genomic sequences of black queen cell virus (BQCV) published in the GenBank, including South Africa (AF183905), South Korea (JX149531), Hungary 10 (EF517515), Poland 4 (EF517519), Poland 5 (EF517520) and Poland 6 (EF517521). Based on the six BQCV strains published in the GenBank, ten pairs of primers were designed in the present study using reverse transcription polymerase chain reaction to obtain the first complete genome sequence of a BQCV strain in China, called the BQCV China-JL1 strain (KP119603). A phylogenetic tree was then built to analyse their genetic relationships. The BQCV China-JL1 strain showed 86-93% similarity with the six strains published in the GenBank. The BQCV China-JL1 strain consisted of 8358 nucleotides (nt). The 5'-proximal open reading frame (ORF1) initiated at nt position 546 and terminated at nt position 4676, ORF3 initiated at nt position 4891 and terminated at nt position 5433, and the 3' proximal ORF (ORF2) was located between nt positions 5750 and 8203. PMID- 27378550 TI - Dopamine D2/3- and MU-opioid receptor antagonists reduce cue-induced responding and reward impulsivity in humans. AB - Increased responding to drug-associated stimuli (cue reactivity) and an inability to tolerate delayed gratification (reward impulsivity) have been implicated in the development and maintenance of drug addiction. Whereas data from animal studies suggest that both the dopamine and opioid system are involved in these two reward-related processes, their role in humans is less clear. Moreover, dopaminergic and opioidergic drugs have not been directly compared with regard to these functions, even though a deeper understanding of the underlying mechanisms might inform the development of specific treatments for elevated cue reactivity and reward impulsivity. In a randomized, double-blind, between-subject design we administered the selective dopamine D2/D3 receptor antagonist amisulpride (400 mg, n=41), the unspecific opioid receptor antagonist naltrexone (50 mg, n=40) or placebo (n=40) to healthy humans and measured cue-induced responding with a Pavlovian-instrumental transfer task and reward impulsivity with a delay discounting task. Mood was assessed using a visual analogue scale. Compared with placebo, amisulpride significantly suppressed cue-induced responding and reward impulsivity. The effects of naltrexone were similar, although less pronounced. Both amisulpride and naltrexone decreased average mood ratings compared with placebo. Our results demonstrate that a selective blockade of dopamine D2/D3 receptors reduces cue-induced responding and reward impulsivity in healthy humans. Antagonizing MU-opioid receptors has similar effects for cue-induced responding and to a lesser extent for reward impulsivity. PMID- 27378552 TI - A highly diverse, desert-like microbial biocenosis on solar panels in a Mediterranean city. AB - Microorganisms colonize a wide range of natural and artificial environments although there are hardly any data on the microbial ecology of one the most widespread man-made extreme structures: solar panels. Here we show that solar panels in a Mediterranean city (Valencia, Spain) harbor a highly diverse microbial community with more than 500 different species per panel, most of which belong to drought-, heat- and radiation-adapted bacterial genera, and sun irradiation adapted epiphytic fungi. The taxonomic and functional profiles of this microbial community and the characterization of selected culturable bacteria reveal the existence of a diverse mesophilic microbial community on the panels' surface. This biocenosis proved to be more similar to the ones inhabiting deserts than to any human or urban microbial ecosystem. This unique microbial community shows different day/night proteomic profiles; it is dominated by reddish pigment- and sphingolipid-producers, and is adapted to withstand circadian cycles of high temperatures, desiccation and solar radiation. PMID- 27378553 TI - Left Ventricular Unloading After Acute Myocardial Infarction Reduces MMP/JNK Associated Apoptosis and Promotes FAK Cell-Survival Signaling. AB - BACKGROUND: The mechanism underlying left ventricular remodeling and reverse remodeling in the setting of mechanical support following acute myocardial infarction (MI) is unclear. We tested the hypothesis that left ventricular assist device (LVAD) unloading can decrease apoptotic signals after MI. METHODS: An MI model was created in 16 sheep by coronary artery ligation. Eight were unloaded with a LVAD during the first 2 weeks after MI and observed for 10 more weeks. Myocardial tissue was collected from the nonischemic adjacent zone and the remote zone. Proteins in the apoptotic matrix metalloproteinases (MMPs)-2/c-Jun N terminal kinase (JNK) and prosurvival beta1D-integrin/focal adhesion kinase (FAK) pathway were quantified. RESULTS: Increased TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) positive nuclei were observed in the MI group and to a lesser extent in the LVAD group (6.18 +/- 0.26 versus 0.82 +/- 0.18; p < 0.05). Pro-MMP-2, MMP-2, JNK, and phosphorylated (p)-JNK were all elevated in the adjacent zone of the MI-only group but not in the adjacent zone of the LVAD-supported group. There were higher levels of prosurvival p-FAK in the LVAD-supported group than in the MI group. CONCLUSIONS: MMP-2/JNK apoptotic and beta1D-integrin/FAK survival pathways are activated in the nonischemic adjacent zone after MI in adult sheep. LVAD unloading of approximately 50% cardiac output for 2 weeks attenuates remodeling in part by its negative effect on stretch induced apoptosis and inhibition of MMP-2 activity. PMID- 27378555 TI - Structural Design Principle of Small-Molecule Organic Semiconductors for Metal Free, Visible-Light-Promoted Photocatalysis. AB - Herein, we report on the structural design principle of small-molecule organic semiconductors as metal-free, pure organic and visible light-active photocatalysts. Two series of electron-donor and acceptor-type organic semiconductor molecules were synthesized to meet crucial requirements, such as 1) absorption range in the visible region, 2) sufficient photoredox potential, and 3) long lifetime of photogenerated excitons. The photocatalytic activity was demonstrated in the intermolecular C-H functionalization of electron-rich heteroaromates with malonate derivatives. A mechanistic study of the light induced electron transport between the organic photocatalyst, substrate, and the sacrificial agent are described. With their tunable absorption range and defined energy-band structure, the small-molecule organic semiconductors could offer a new class of metal-free and visible light-active photocatalysts for chemical reactions. PMID- 27378554 TI - Does Platelet Reactivity Predict Bleeding in Patients Needing Urgent Coronary Artery Bypass Grafting During Dual Antiplatelet Therapy? AB - BACKGROUND: Up to 15% of patients require coronary artery bypass grafting (CABG) during dual antiplatelet therapy. Available evidence suggests an association between platelet reactivity and CABG-related bleeding. However, platelet reactivity cutoffs for bleeding remain elusive. We sought to explore the association between platelet reactivity and bleeding. METHODS: Patients on aspirin and a P2Y12 receptor inhibitor within 48 hours before isolated CABG (n = 149) were enrolled in this prospective study. Blood was drawn 2 to 4 hours preoperatively and platelet reactivity assessed by light transmittance aggregometry (LTA), vasodilator-stimulated phosphoprotein (VASP) assay, Multiplate analyzer and Innovance PFA2Y. The primary endpoint was calculated red blood cell loss computed as follows: (blood volume * preoperative hematocrit * 0.91) - (blood volume * hematocrit * 0.91 on postoperative day 5) + (mL of transfused red blood cells * 0.59). RESULTS: Preoperative platelet reactivity was low [median (interquartile range): LTA: 20 (9-28)%; VASP-PRI: 39 (15-73)%; Multiplate adenosine phosphate test: 16 (12-22) U*min]. Innovance PFA2Y >=300 seconds, 72%. Median (IQR) red blood cell loss in patients in first the LTA tertile was 1,449 (1,020 to 1,754) mL compared with 1,107 (858 to 1,512) mL and 1,075 (811 to 1,269) mL in those in the second and third tertiles, respectively (p < 0.004). Bleeding Academic Research Consortium (BARC)-4 bleeding differed between tertiles (62% versus 46% versus 36%; p = 0.037). In a multivariable linear regression model, aspirin dose >=300 mg, cardiopulmonary bypass time, EuroSCORE, and tertile distribution of platelet reactivity were significantly associated with red blood cell loss. CONCLUSIONS: A gradual decrease in red blood cell loss and BARC-4 bleeding occurs with increasing platelet reactivity in patients on antiplatelet therapy undergoing CABG. Our findings support current guidelines to determine time of surgery based on an objective measurement of platelet function (Platelet Inhibition and Bleeding in Patients Undergoing Emergent Cardiac Surgery; clinicaltrials.gov NCT01468597). PMID- 27378556 TI - Can hyaluronan injections augment deficient papillae at implant-supported crowns in the anterior maxilla? A randomized controlled clinical trial with 6 months follow-up. AB - OBJECTIVES: The present randomized controlled trial aimed to assess the effect of hyaluronan (HY) injections to augment deficient interproximal papillae at implant supported crowns in the anterior maxilla. METHODS: Twenty-two patients with a deficient papilla in the anterior maxilla next to an implant-supported crown were randomly assigned to receive twice either HY (test) or saline solution (control) injection. The following parameters were recorded prior to injection (baseline) and 3 and 6 months after injection: distance between the papilla tip and contact point (PT-CP), modified papilla index score (MPIS), and standard clinical periodontal parameters. Pain level after injection was recorded on a visual analogue scale (VAS). The deficient area was evaluated on clinical photographs, and the esthetic appearance was recorded on a VAS. Differences in mucosal volume were assessed after 3 months by intraoral scans. The bone level was assessed on periapical radiographs. RESULTS: No differences were observed between groups, neither at baseline nor at 3 and 6 months post-treatment. Mean PT-CP ranged between 1.8 mm and 2.3 mm without significant differences between groups or over time within groups; MPIS was 2 for all patients at all time points. Similarly, insignificant differences between groups or time points were observed for deficient area, gingival volume changes, bone level, and esthetic appearance. There were no differences in pain level between groups during injection, but discomfort after injection lasted longer in the test group. CONCLUSIONS: Injection of HY adjacent to maxillary anterior implant-supported crowns did not result in any clinical conspicuous volume augmentation of deficient papillae. PMID- 27378557 TI - Dimercaptosuccinic acid scan or ultrasound in screening for vesicoureteral reflux among children with urinary tract infections. AB - BACKGROUND: There is considerable interest in detecting vesicoureteral reflux (VUR) because its presence, especially when severe, has been linked to an increased risk of urinary tract infections and renal scarring. Voiding cystourethrography (VCUG), also known as micturating cystourethrography, is the gold standard for the diagnosis of VUR, and the grading of its severity. Because VCUG requires bladder catheterisation and exposes children to radiation, there has been a growing interest in other screening strategies that could identify at risk children without the risks and discomfort associated with VCUG. OBJECTIVES: The objective of this review is to evaluate the accuracy of two alternative imaging tests - the dimercaptosuccinic acid renal scan (DMSA) and renal-bladder ultrasound (RBUS) - in diagnosing VUR and high-grade VUR (Grade III-V VUR). SEARCH METHODS: We searched MEDLINE, EMBASE, BIOSIS, and the Cochrane Register of Diagnostic Test Accuracy Studies from 1985 to 31 March 2016. The reference lists of relevant review articles were searched to identify additional studies not found through the electronic search. SELECTION CRITERIA: We considered published cross-sectional or cohort studies that compared the results of the index tests (DMSA scan or RBUS) with the results of radiographic VCUG in children less than 19 years of age with a culture-confirmed urinary tract infection. DATA COLLECTION AND ANALYSIS: Two authors independently applied the selection criteria to all citations and independently abstracted data. We used the bivariate model to calculate summary sensitivity and specificity values. MAIN RESULTS: A total of 42 studies met our inclusion criteria. Twenty studies reported data on the test performance of RBUS in detecting VUR; the summary sensitivity and specificity estimates were 0.44 (95% CI 0.34 to 0.54) and 0.78 (95% CI 0.68 to 0.86), respectively. A total of 11 studies reported data on the test performance of RBUS in detecting high-grade VUR; the summary sensitivity and specificity estimates were 0.59 (95% CI 0.45 to 0.72) and 0.79 (95% CI 0.65 to 0.87), respectively. A total of 19 studies reported data on the test performance of DMSA in detecting VUR; the summary sensitivity and specificity estimates were 0.75 (95% CI 0.67 to 0.81) and 0.48 (95% CI 0.38 to 0.57), respectively. A total of 10 studies reported data on the accuracy of DMSA in detecting high-grade VUR. The summary sensitivity and specificity estimates were 0.93 (95% CI 0.77 to 0.98) and 0.44 (95% CI 0.33 to 0.56), respectively. AUTHORS' CONCLUSIONS: Neither the renal ultrasound nor the DMSA scan is accurate enough to detect VUR (of all grades). Although a child with a negative DMSA test has an < 1% probability of having high grade VUR, performing a screening DMSA will result in a large number of children falsely labelled as being at risk for high-grade VUR. Accordingly, the usefulness of the DMSA as a screening test for high-grade VUR should be questioned. PMID- 27378558 TI - Acetyl-l-carnitine restores synaptic transmission and enhances the inducibility of stable LTP after oxygen-glucose deprivation. AB - Hypoxic circumstances result in functional and structural impairments of the brain. Oxygen-glucose deprivation (OGD) on hippocampal slices is a technique widely used to investigate the consequences of ischemic stroke and the potential neuroprotective effects of different drugs. Acetyl-l-carnitine (ALC) is a naturally occurring substance in the body, and it can therefore be administered safely even in relatively high doses. In previous experiments, ALC pretreatment proved to be effective against global hypoperfusion. In the present study, we investigated whether ALC can be protective in an OGD model. We are not aware of any earlier study in which the long-term potentiation (LTP) function on hippocampal slices was measured after OGD. Therefore, we set out to determine whether an effective ALC concentration has an effect on synaptic plasticity after OGD in the hippocampal CA1 subfield of rats. A further aim was to investigate the mechanism underlying the protective effect of this compound. The experiments revealed that ALC is neuroprotective against OGD in a dose-dependent manner, which is manifested not only in the regeneration of the impaired synaptic transmission after the OGD, but also in the inducibility and stability of the LTP. In the case of the most effective concentration of ALC (500MUM), use of a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) revealed that the PI3K/Akt signaling pathway has a key role in the restoration of the synaptic transmission and plasticity reached by ALC treatment. PMID- 27378559 TI - Guess who's coming to dinner: Brain signatures of racially biased and politically correct behaviors. AB - The ability to share feelings with those of someone in pain is affected by the racial difference between the target and the onlooker. A differential empathic activation for race (DEAR effect) in favor of in-group members has been documented in the brain pain matrix. However, we are also capable of unbiased responses that manifest politically correct behaviors toward people of a different race. To address the neurofunctional signatures underlying both the DEAR effect and the manifestation of politically correct behaviors, we scanned with fMRI Caucasian participants while watching African or Caucasian actors touched by either a rubber eraser or a needle. Participants were instructed to empathize with the actors during the video presentation (stimulus phase) and to explicitly judge the pain level experienced by the actors (response phase). During the stimulus phase, we found a typical DEAR effect within the pain-matrix. This effect correlated with the level of implicit racial bias as measured by the IAT. On the other hand, during the response phase a significant out-group specific DEAR effect emerged in the prefrontal cortices. This latter effect was coupled with a revealing behavioral pattern: while the magnitude of the painful experience attributed to Caucasians and Africans was the same, our participants were significantly slower when judging the pain experience of the African actors. We propose a model that logically integrates these two contrasting forces at the neurobiological and behavioral level. PMID- 27378560 TI - Preliminary evaluation of a gel tube agglutination major cross-match method in dogs. AB - BACKGROUND: A major cross-match gel tube test is available for use in dogs yet has not been clinically evaluated. OBJECTIVES: This study compared cross-match results obtained using the gel tube and the standard tube methods for canine samples. METHODS: Study 1 included 107 canine sample donor-recipient pairings cross-match tested with the RapidVet-H method gel tube test and compared results with the standard tube method. Additionally, 120 pairings using pooled sera containing anti-canine erythrocyte antibody at various concentrations were tested with leftover blood from a hospital population to assess sensitivity and specificity of the gel tube method in comparison with the standard method. RESULTS: The gel tube method had a good relative specificity of 96.1% in detecting lack of agglutination (compatibility) compared to the standard tube method. Agreement between the 2 methods was moderate. Nine of 107 pairings showed agglutination/incompatibility on either test, too few to allow reliable calculation of relative sensitivity. Fifty percent of the gel tube method results were difficult to interpret due to sample spreading in the reaction and/or negative control tubes. CONCLUSIONS: The RapidVet-H method agreed with the standard cross-match method on compatible samples, but detected incompatibility in some sample pairs that were compatible with the standard method. Evaluation using larger numbers of incompatible pairings is needed to assess diagnostic utility. The gel tube method results were difficult to categorize due to sample spreading. Weak agglutination reactions or other factors such as centrifuge model may be responsible. PMID- 27378561 TI - Isolated Disruption of the Right Coronary Artery Following a Steam Pop during Cavotricuspid Linear Ablation with a Contact Force Catheter. AB - A 70-year-old woman with persistent atrial fibrillation underwent pulmonary vein isolation and linear ablation with a contact sensor catheter. During cavotricuspid isthmus ablation, a steam pop resulted in cardiac tamponade, and the patient developed severe hypotension despite successful pericardial puncture and minimal residual pericardial effusion. Right coronary artery angiography revealed extravasal contrast medium accumulation posterior of the Crux Cordis. Emergent cardiac surgery confirmed isolated disruption of the artery in the absence of additional heart perforation. Although contact sensor catheters may reduce complications, steam pops can still occur and result in dramatic complications. PMID- 27378562 TI - Diaphragmatic Myopotential Oversensing Caused by Change in Implantable Cardioverter Defibrillator Sensing Bandpass Filter. AB - Diaphragmatic myopotential oversensing (DMO) causes inhibition of pacing and inappropriate detection of ventricular fibrillation in implantable cardioverter defibrillators (ICDs). It occurs almost exclusively with integrated bipolar leads and is extremely rare with dedicated bipolar leads. If DMO cannot be corrected by reducing programmed sensitivity, ventricular lead revision is often required. The new Low Frequency Attenuation (LFA) filter in St. Jude Medical ICDs (St. Jude Medical, Sylmar, CA, USA) alters the sensing bandpass to reduce T-wave oversensing. This paper aims to present the LFA filter as a reversible cause of DMO. Unnecessary lead revision can be avoided by the simple programming solution of deactivating this LFA filter. PMID- 27378563 TI - Erratum. PMID- 27378565 TI - HMGB1 as biomarker and drug target. AB - High Mobility Group Box 1 protein was discovered as a nuclear protein, but it has a "second life" outside the cell where it acts as a damage-associated molecular pattern. HMGB1 is passively released or actively secreted in a number of diseases, including trauma, chronic inflammatory disorders, autoimmune diseases and cancer. Extracellular HMGB1 triggers and sustains the inflammatory response by inducing cytokine release and by recruiting leucocytes. These characteristics make extracellular HMGB1 a key molecular target in multiple diseases. A number of strategies have been used to prevent HMGB1 release or to inhibit its activities. Current pharmacological strategies include antibodies, peptides, decoy receptors and small molecules. Noteworthy, salicylic acid, a metabolite of aspirin, has been recently found to inhibit HMGB1. HMGB1 undergoes extensive post translational modifications, in particular acetylation and oxidation, which modulate its functions. Notably, high levels of serum HMGB1, in particular of the hyper-acetylated and disulfide isoforms, are sensitive disease biomarkers and are associated with different disease stages. In the future, the development of isoform-specific HMGB1 inhibitors may potentiate and fine-tune the pharmacological control of inflammation. We review here the current therapeutic strategies targeting HMGB1, in particular the emerging and relatively unexplored small molecules-based approach. PMID- 27378564 TI - Gbetagamma subunits-Different spaces, different faces. AB - Gbetagamma subunits play key roles in modulation of canonical effectors in G protein-coupled receptor (GPCR)-dependent signalling at the cell surface. However, a number of recent studies of Gbetagamma function have revealed that they regulate a large number of molecules at distinct subcellular sites. These novel, non-canonical Gbetagamma roles have reshaped our understanding of how important Gbetagamma signalling is compared to our original notion of Gbetagamma subunits as simple negative regulators of Galpha subunits. Gbetagamma dimers have now been identified as regulators of transcription, anterograde and retrograde trafficking and modulators of second messenger molecule generation in intracellular organelles. Here, we review some recent advances in our understanding of these novel non-canonical roles of Gbetagamma. PMID- 27378566 TI - In silico pharmacology: Drug membrane partitioning and crossing. AB - Over the past decade, molecular dynamics (MD) simulations have become particularly powerful to rationalize drug insertion and partitioning in lipid bilayers. MD simulations efficiently support experimental evidences, with a comprehensive understanding of molecular interactions driving insertion and crossing. Prediction of drug partitioning is discussed with respect to drug families (anesthetics; beta-blockers; non-steroidal anti-inflammatory drugs; antioxidants; antiviral drugs; antimicrobial peptides). To accurately evaluate passive permeation coefficients turned out to be a complex theoretical challenge; however the recent methodological developments based on biased MD simulations are particularly promising. Particular attention is paid to membrane composition (e.g., presence of cholesterol), which influences drug partitioning and permeation. Recent studies concerning in silico models of membrane proteins involved in drug transport (influx and efflux) are also reported here. These studies have allowed gaining insight in drug efflux by, e.g., ABC transporters at an atomic resolution, explicitly accounting for the mandatory forces induced by the surrounded lipid bilayer. Large-scale conformational changes were thoroughly analyzed. PMID- 27378567 TI - Regulation of soluble guanylyl cyclase redox state by hydrogen sulfide. AB - Soluble guanylate cyclase (sGC) is a receptor for nitric oxide (NO). Binding of NO to ferrous (Fe(2+)) heme increases its catalytic activity, leading to the production of cGMP from GTP. Hydrogen sulfide (H2S) is a signaling molecule that exerts both direct and indirect anti-oxidant effects. In the present, study we aimed to determine whether H2S could regulate sGC redox state and affect its responsiveness to NO-releasing agents and sGC activators. Using cultured rat aortic smooth muscle cells, we observed that treatment with H2S augmented the response to the NO donor DEA/NO, while attenuating the response to the heme independent activator BAY58-2667 that targets oxidized sGC. Similarly, overexpression of H2S-synthesizing enzyme cystathionine-gamma lyase reduced the ability of BAY58-2667 to promote cGMP accumulation. In experiments with phenylephrine-constricted mouse aortic rings, treatment with rotenone (a compound that increases ROS production), caused a rightward shift of the DEA/NO concentration-response curve, an effect partially restored by H2S. When rings were pre-treated with H2S, the concentration-response curve to BAY 58-2667 shifted to the right. Using purified recombinant human sGC, we observed that treatment with H2S converted ferric to ferrous sGC enhancing NO-donor-stimulated sGC activity and reducing BAY 58-2667-triggered cGMP formation. The present study identified an additional mechanism of cross-talk between the NO and H2S pathways at the level of redox regulation of sGC. Our results provide evidence that H2S reduces sGC heme Fe, thus, facilitating NO-mediated cellular signaling events. PMID- 27378568 TI - Plasma vemurafenib exposure and pre-treatment hepatocyte growth factor level are two factors contributing to the early peripheral lymphocytes depletion in BRAF mutated melanoma patients. AB - The therapeutic response to vemurafenib, a BRAF serine-threonine kinase inhibitor, exhibits large variations between patients. Evaluation of factors predicting the clinical efficacy of vemurafenib may help to identify patients at high risk of non-response in the early phase of treatment. The aim of this study was to analyze the pharmacokinetics of vemurafenib by a population approach and to evaluate the relationship between plasma drug exposure and pre-treatment plasma hepatocyte growth factor (HGF) levels with clinical effects (progression free survival (PFS), peripheral lymphocytes depletion) in patients with metastatic BRAFV600 mutated melanoma treated with single agent vemurafenib. Concentration-time data (n=332) obtained in 44 patients were analyzed using the NONMEM program. Pre-treatment plasma levels of HGF (n=36) were assayed by ELISA method. A Cox model was used to identify prognostic factors associated with progression-free survival (PFS), and a linear regression to identify factors contributing to the depletion of peripheral lymphocytes at day 15. Steady-state pharmacokinetics of vemurafenib was described by a one compartment model with first order absorption and first order elimination. None of the tested covariates explained the inter-patient variability in CL/F. A significant decrease in total lymphocytes count was observed within the first 15days (median ratio Day15/Day0=0.66, p<0.0001). Patients with Day15/Day0 ratio below 0.66 had longer PFS (14 vs 4 months, HR=0.41, CI95%=[0.15-0.77], p=0.0095). In the multivariate Cox model analysis, ECOG PS was the only parameter independently associated with PFS (grade 1 vs 0, HR=3.26, CI95%=[1.29-8.22], p=0.01 and grade >=2 vs 0, HR=4.77, CI95%=[1.52-14.95], p=0.007). Plasma vemurafenib exposure (p=0.046) and pre-treatment HGF levels (p=0.003) were independently associated with the total lymphocyte ratio Day15/Day0. These findings show that plasma vemurafenib exposure and pre-treatment HGF levels are two factors contributing to the early peripheral lymphocytes depletion which itself is associated with PFS. PMID- 27378569 TI - Serum free thiols in chronic heart failure. AB - Oxidative stress is a key element of the pathophysiology of heart failure (HF). As free thiols are readily oxidized by reactive oxygen and sulfur species, their circulating level may directly reflect the systemic redox status. This study addresses the role of serum free thiols in chronic HF, which is of particular interest as free thiols are amenable to therapeutic modulation and thus are a potential target for therapy. Free thiols were measured in serum of 101 previously characterized stable chronic HF patients (93% male, age 63.7+/-10.0y, left ventricular ejection fraction 34.6+/-8.2%), adjusted for total serum protein, and subsequently analysed for associations with clinical and outcome parameters. The mean serum free thiol concentration was 3.6+/-0.5MUM/g protein. Patients with above-average levels were younger, had better renal function, lower levels of NT-proBNP and PTH, and higher levels of cholesterol. Furthermore, above average levels were associated with favourable disease outcome, i.e. a decreased rehospitalisation rate and increased patient survival (HR 0.27 (95% CI 0.11 0.62), P=0.002) independent of associated clinical parameters, age and PTH. After adjustment for cholesterol or established prognostic factors in HF, eGFR and NT proBNP the association was no longer significant, suggesting involvement of these variables in a common pathophysiological pathway. This exploratory study demonstrates favourable associations of serum free thiols with markers of HF severity and prognosis as well as disease outcome, which should be further investigated in larger prospective studies. Restoring redox status by therapeutic modulation of free thiols may be a promising strategy to improve disease outcome in CHF. PMID- 27378570 TI - Pharmacological postconditioning against myocardial infarction with a slow releasing hydrogen sulfide donor, GYY4137. AB - Exogenous hydrogen sulfide (H2S) protects against myocardial ischemia/reperfusion injury but the mechanism of action is unclear. The present study investigated the effect of GYY4137, a slow-releasing H2S donor, on myocardial infarction given specifically at reperfusion and the signalling pathway involved. Thiobutabarbital anesthetised rats were subjected to 30min of left coronary artery occlusion and 2h reperfusion. Infarct size was assessed by tetrazolium staining. In the first study, animals randomly received either no treatment or GYY4137 (26.6, 133 or 266MUmolkg(-1)) by intravenous injection 10min before reperfusion. In a second series, involvement of PI3K and NO signalling were interrogated by concomitant administration of LY294002 or L-NAME respectively and the effects on the phosphorylation of Akt, eNOS, GSK-3beta and ERK1/2 during early reperfusion were assessed by immunoblotting. GYY4137 266MUmolkg(-1) significantly limited infarct size by 47% compared to control hearts (P<0.01). In GYY4137-treated hearts, phosphorylation of Akt, eNOS and GSK-3beta was increased 2.8, 2.2 and 2.2 fold respectively at early reperfusion. Co-administration of L-NAME and GYY4137 attenuated the cardioprotection afforded by GYY4137, associated with attenuated phosphorylation of eNOS. LY294002 totally abrogated the infarct-limiting effect of GYY4137 and inhibited Akt, eNOS and GSK-3beta phosphorylation. These data are the first to demonstrate that GYY4137 protects the heart against lethal reperfusion injury through activation of PI3K/Akt signalling, with partial dependency on NO signalling and inhibition of GSK-3beta during early reperfusion. H2S-based therapeutic approaches may have value as adjuncts to reperfusion in the treatment of acute myocardial infarction. PMID- 27378572 TI - Deaths: Final Data for 2014. AB - Objectives-This report presents final 2014 data on U.S. deaths, death rates, life expectancy, infant mortality, and trends, by selected characteristics such as age, sex, Hispanic origin, race, state of residence, and cause of death. PMID- 27378571 TI - Screening for genotypic and phenotypic variations in CYP450 activity in patients with therapeutic problems in a psychiatric setting, a retrospective study. AB - OBJECTIVES: This retrospective study aimed to assess to what extent an adverse drug reaction (ADR), an abnormal therapeutic drug monitoring (TDM) or a non response, was attributable to an abnormal cytochrome P450 activity in a psychiatric setting. METHOD: We collected the results of investigations performed in these situations related to psychotropic drugs between January 2005 and November 2014. Activities of different cytochrome P450 were assessed by genotyping and/or phenotyping. Two experienced clinical pharmacologists assessed independently the possible association between the event and the results of the investigations. RESULTS: One hundred and thirty eight clinical or biological situations had a complete assessment of all major metabolic pathways of the target drug. A majority of clinical or biological situations were observed with antidepressants (n=93, 67.4%), followed by antipsychotics (n=28, 20.3%), benzodiazepines and hypnotics (n=13, 9.4%), and psychostimulants (n=4, 2.9%). Genotype and/or phenotype determination was mainly performed because of ADRs (n=68, 49.3%) or non-response (n=46, 33.3%). Inter-rate reliability of the scoring system between the pharmacologists was excellent (kappa=0.94). The probability of an association between ADR, TDM or non-response and metabolic status was rated as intermediate to high in 34.7% of all cases, with proportions of 30.4% and 36.7%, for non-response and ADR respectively. CONCLUSION: When indicated by clinical pharmacologists, ADR, TDM or non-response may be attributable to a variation of the metabolic status with an intermediate to high probability in 34.7% of patients, based on the congruent assessment made by two clinical pharmacologists. Further studies assessing the clinical relevance of prospective explorations and clarifying the appropriate method according to the clinical context are needed. PMID- 27378573 TI - Effect of colchicine in prevention of pericardial effusion and atrial fibrillation: a meta-analysis. AB - Randomized, controlled trials (RCTs) have assessed the effect of colchicine therapy in prevention of pericardial effusion (PE) and atrial fibrillation (AF). However, the effects are still inconclusive. PubMed, Cochrane Library, Google Scholar, and EMBASE database were searched. Primary outcome was the risk of PE and AF. Ten RCTs with 1981 patients and a mean follow-up of 12.6 months were included. Colchicine therapy was not associated with a significantly lower risk of post-operative PE (RR, 0.89; 95 % CI 0.70-1.13; p = 0.33, I (2) = 72.8 %) and AF (RR, 0.77; 95 % CI 0.52-1.13; p = 0.18, I (2) = 47.3 %). However, rates of pericarditis recurrence, symptoms persistence, and pericarditis-related hospitalization were significantly decreased with colchicine treatment. In addition, cardiac tamponade occurrence was similar between groups, and adverse events were significantly higher in the colchicine group. Colchicine may not significantly decrease the post-operative risk of PE and AF. However, only limited studies about patients undergoing cardiac surgery provide data about PE and AF. PMID- 27378574 TI - The prosegment catalyzes native folding of Plasmodium falciparum plasmepsin II. AB - Plasmepsin II is a malarial pepsin-like aspartic protease produced as a zymogen containing an N-terminal prosegment domain that is removed during activation. Despite structural similarities between active plasmepsin II and pepsin, their prosegments adopt different conformations in the respective zymogens. In contrast to pepsinogen, the proplasmepsin II prosegment is 80 residues longer, contains a transmembrane region and is non-essential for recombinant expression in an active form, thus calling into question the prosegment's precise function. The present study examines the role of the prosegment in the folding mechanism of plasmepsin II. Both a shorter (residues 77-124) and a longer (residues 65-124) prosegment catalyze plasmepsin II folding at rates more than four orders of magnitude faster compared to folding without prosegment. Native plasmepsin II is kinetically trapped and requires the prosegment both to catalyze folding and to shift the folding equilibrium towards the native conformation. Thus, despite low sequence identity and distinct zymogen conformations, the folding landscapes of plasmepsin II and pepsin, both with and without prosegment, are qualitatively identical. These results imply a conserved and unusual feature of the pepsin-like protease topology that necessitates prosegment-assisted folding. PMID- 27378575 TI - Structural characterization of peptidyl-tRNA hydrolase from Mycobacterium smegmatis by NMR spectroscopy. AB - BACKGROUND: Accumulation of toxic peptidyl-tRNAs in the bacterial cytoplasm is averted by the action of peptidyl-tRNA hydrolase (Pth), which cleaves peptidyl tRNA into free tRNA and peptide. NMR studies are needed for a protein homolog with a complete crystal structure, for comparison with the NMR structure of Mycobacterium tuberculosis Pth. METHODS: The structure and dynamics of Mycobacterium smegmatis Pth (MsPth) were characterized by NMR spectroscopy and MD simulations. The thermal stability of MsPth was characterized by DSC. RESULTS: MsPth NMR structure has a central mixed seven stranded beta-sheet that is enclosed by six alpha-helices. NMR relaxation and MD simulations studies show that most of the ordered regions are rigid. Of the substrate binding segments, the gate loop is rigid, the base loop displays slow motions, while the lid loop displays fast timescale motions. MsPth displays high thermal stability characterized by a melting temperature of 61.71 degrees C. CONCLUSION: The NMR structure of MsPth shares the canonical Pth fold with the NMR structure of MtPth. The motional characteristics for the lid region, the tip of helix alpha3, and the gate region, as indicated by MD simulations and NMR data, are similar for MsPth and MtPth. However, MsPth has relatively less rigid base loop and more compactly packed helices alpha5 and alpha6. The packing and the dynamic differences appear to be an important contributing factor to the thermal stability of MsPth, which is significantly higher than that of MtPth. SIGNIFICANCE: MsPth structure consolidates our understanding of the structure and dynamics of bacterial Pth proteins. PMID- 27378576 TI - IMAGING DIAGNOSIS-A LUMINAL LAMINATED DEBRIS BALL IN THE URINARY BLADDER OF A DOG. AB - A 5-year-old dog presented with pollakiuria and urinary incontinence. Abdominal radiographs revealed an oval, multilayered structure with soft tissue opacity and gas lucency in the urinary bladder. Ultrasonography showed an oval luminal structure with hyper- and hypoechoic layers and internal reverberation artifacts. Following cystotomy, the hemisected plane showed a layered, pale whitish matrix with a gas layer around the core. Histopathological examination showed no evidence of cells, bacteria, or fungi. The core and laminae comprised fibrinous and mineral debris. A final diagnosis of a freely floating, gas-filled laminated debris ball was made. PMID- 27378577 TI - Daclatasvir plasma level and resistance selection in HIV patients with hepatitis C virus cirrhosis treated with daclatasvir, sofosbuvir, and ribavirin. AB - OBJECTIVES: Effective treatment with direct-acting antiviral drugs against hepatitis C virus (HCV) is a medical need in cirrhotic HIV-HCV co-infected patients. METHODS: This study investigated the plasma levels of daclatasvir (DCV) and ribavirin (RBV) in HIV-HCV co-infected subjects treated with DCV, sofosbuvir, and RBV. Drug concentrations were quantified using validated high-performance liquid chromatography methods with ultraviolet detection. The HCV non-structural protein 5A and non-structural protein 5B coding regions were analyzed by population-based sequencing. RESULTS: DCV was dosed at week 4 and at week 8 of treatment, and RBV at week 8. One patient had the lowest DCV level, corresponding to 32.7% of the overall median value of the other patients at week 4 and about 40% at week 8. The Y93H variant was detected in this subject at weeks 8, 16, and 20 of treatment, but not before treatment or at day 2, and the patient experienced virological failure. Another subject with the Y93H variant at baseline and appropriate DCV levels had HCV RNA <12 IU/ml at week 12 and undetectable at week 16. CONCLUSIONS: Sub-optimal DCV drug levels allow the selection of resistance-associated variants and fail to contribute to antiviral activity. No definite reason for the low DCV level was found. Quantifying the drug is suggested in difficult-to-treat patients. PMID- 27378578 TI - Safety of reduced antibiotic prescribing for self limiting respiratory tract infections in primary care: cohort study using electronic health records. AB - OBJECTIVE: To determine whether the incidence of pneumonia, peritonsillar abscess, mastoiditis, empyema, meningitis, intracranial abscess, and Lemierre's syndrome is higher in general practices that prescribe fewer antibiotics for self limiting respiratory tract infections (RTIs). DESIGN: Cohort study. SETTING: 610 UK general practices from the UK Clinical Practice Research Datalink. PARTICIPANTS: Registered patients with 45.5 million person years of follow-up from 2005 to 2014. EXPOSURES: Standardised proportion of RTI consultations with antibiotics prescribed for each general practice, and rate of antibiotic prescriptions for RTIs per 1000 registered patients. MAIN OUTCOME MEASURES: Incidence of pneumonia, peritonsillar abscess, mastoiditis, empyema, meningitis, intracranial abscess, and Lemierre's syndrome, adjusting for age group, sex, region, deprivation fifth, RTI consultation rate, and general practice. RESULTS: From 2005 to 2014 the proportion of RTI consultations with antibiotics prescribed decreased from 53.9% to 50.5% in men and from 54.5% to 51.5% in women. From 2005 to 2014, new episodes of meningitis, mastoiditis, and peritonsillar abscess decreased annually by 5.3%, 4.6%, and 1.0%, respectively, whereas new episodes of pneumonia increased by 0.4%. Age and sex standardised incidences for pneumonia and peritonsillar abscess were higher for practices in the lowest fourth of antibiotic prescribing compared with the highest fourth. The adjusted relative risk increases for a 10% reduction in antibiotic prescribing were 12.8% (95% confidence interval 7.8% to 17.5%, P<0.001) for pneumonia and 9.9% (5.6% to 14.0%, P<0.001) for peritonsillar abscess. If a general practice with an average list size of 7000 patients reduces the proportion of RTI consultations with antibiotics prescribed by 10%, then it might observe 1.1 (95% confidence interval 0.6 to 1.5) more cases of pneumonia each year and 0.9 (0.5 to 1.3) more cases of peritonsillar abscess each decade. Mastoiditis, empyema, meningitis, intracranial abscess, and Lemierre's syndrome were similar in frequency at low prescribing and high prescribing practices. CONCLUSIONS: General practices that adopt a policy to reduce antibiotic prescribing for RTIs might expect a slight increase in the incidence of treatable pneumonia and peritonsillar abscess. No increase is likely in mastoiditis, empyema, bacterial meningitis, intracranial abscess, or Lemierre's syndrome. Even a substantial reduction in antibiotic prescribing was predicted to be associated with only a small increase in numbers of cases observed overall, but caution might be required in subgroups at higher risk of pneumonia. PMID- 27378580 TI - Enhanced recovery care after colorectal surgery in elderly patients. Compliance and outcomes of a multicenter study from the Spanish working group on ERAS. AB - PURPOSE: ERAS (enhanced recovery after surgery) programs have proven to reduce morbidity and hospital stay in colorectal surgery. However, the feasibility of these programs in elderly patients has been questioned. The aim of this study is to assess the implementation and outcomes of an ERAS program for colorectal cancer in elderly patients. METHODS: This is a multicenter observational study of a cohort of elderly patients undergoing colorectal surgery within an ERAS program. A total of 188 consecutive patients over 70 years who underwent elective colorectal surgery within an ERAS program at three institutions during a 2-year period were included. The compliance with the ERAS protocol interventions was measure. Complications were evaluated according to Clavien-Dindo classification. Data on length of stay and readmission rates were analyzed. RESULTS: Early intake and early mobilization were the most successfully carried out interventions. There was a global compliance rate of 56 % of patients for whom compliance was achieved with all measured interventions. The median hospital length of stay was 6 days. Almost 60 % of patients had no complications, 24 % had minor complications while 13 % had major complications; of them, 8 % patients were reoperated. The readmission rate was 6.4 %. CONCLUSIONS: ERAS after colorectal surgery in elderly patients presents as safe and feasible based on good reported outcomes of compliance rates, complications, readmissions, and needs for reoperation. PMID- 27378579 TI - Notch signaling in lung diseases: focus on Notch1 and Notch3. AB - Notch signaling is an evolutionarily conserved cell-cell communication mechanism that plays a key role in lung homeostasis, injury and repair. The loss of regulation of Notch signaling, especially Notch1 and Notch3, has recently been linked to the pathogenesis of important lung diseases, in particular, chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis, pulmonary arterial hypertension (PAH), lung cancer and lung lesions in some congenital diseases. This review focuses on recent advances related to the mechanisms and the consequences of aberrant or absent Notch1/3 activity in the initiation and progression of lung diseases. Our increasing understanding of this signaling pathway offers great hope that manipulating Notch signaling may represent a promising alternative complementary therapeutic strategy in the future. PMID- 27378581 TI - Making It Safe to Grow Old: A Financial Simulation Model for Launching MediCaring Communities for Frail Elderly Medicare Beneficiaries. AB - POLICY POINTS: At age 65, the average man and woman can respectively expect 1.5 years and 2.5 years of requiring daily help with "activities of daily living." Available services fail to match frail elders' needs, thereby routinely generating errors, unreliability, unwanted services, unmet needs, and high costs. The number of elderly Medicare beneficiaries likely to be frail will triple between 2000 and 2050. Low retirement savings, rising medical and long-term care costs, and declining family caregiver availability portend gaps in badly needed services. The financial simulation reported here for 4 diverse MediCaring Communities shows lower per capita costs. Program savings are substantial and can improve coverage and function of local supportive services within current overall Medicare spending levels. CONTEXT: The Altarum Institute Center for Elder Care and Advanced Illness has developed a reform model, MediCaring Communities, to improve services for frail elderly Medicare beneficiaries through longitudinal care planning, better-coordinated and more desirable medical and social services, and local monitoring and management of a community's quality and supply of services. This study uses financial simulation to determine whether communities could implement the model within current Medicare and Medicaid spending levels, an important consideration to enable development and broad implementation. METHODS: The financial simulation for MediCaring Communities uses 4 diverse communities chosen for adequate size, varying health care delivery systems, and ability to implement reforms and generate data rapidly: Akron, Ohio; Milwaukie, Oregon; northeastern Queens, New York; and Williamsburg, Virginia. For each community, leaders contributed baseline population and program effect estimates that reflected projections from reported research to build the model. FINDINGS: The simulation projected third-year savings between $269 and $537 per beneficiary per month and cumulative returns on investment between 75% and 165%. CONCLUSIONS: The MediCaring Communities financial simulation demonstrates that better care at lower cost for frail elderly Medicare beneficiaries is possible within current financing levels. Long-term success of the initiative will require reinvestment of Medicare savings to bolster nonmedical supportive services in the community. Successful implementation will necessitate waiving certain regulations and developing new infrastructure in pilot communities. This financial simulation methodology will help leadership in other communities to project fiscal performance. Since the MediCaring Communities model also achieves the Centers for Medicare and Medicaid Services' vision for care for frail elders (better care, healthier people, smarter spending) and since these reforms can proceed with limited waivers from Medicare, willing communities should explore implementation and share best practices about how to achieve fundamental service delivery changes that can meet the challenges of a much older population in the 21st century. PMID- 27378582 TI - Burden of Keloid Disease: A Cross-sectional Health-related Quality of Life Assessment. AB - Keloid scars may be painful, itch severely and be cosmetically disturbing. The burden of keloid disease, however, has not yet been determined. This study evaluated the association of keloid disease with health-related quality of life (HRQL) and identified indicators of burden using a cross-sectional survey study, with one disease-specific HRQL measure (Skindex-29) and 2 generic HRQL measures (SF-36 and EQ-5D-5L). A total of 106 keloid patients with no other skin diseases participated in the study. Having keloid disease was associated with a considerable impairment of emotional wellbeing, with most impairment on the emotional and mental HRQL. Pain and itch were the strongest indicators of HRQL impairment in keloid patients. Having painful or itchy keloids was related to low mental and emotional HRQL, implying that patients with keloids require access to effective treatment aimed at alleviating physical symptoms. PMID- 27378583 TI - The contribution of activated peripheral kappa opioid receptors (kORs) in the inflamed knee joint to anti-nociception. AB - The systemic administration of opioids can be used for their strong analgesic effect. However, extensive activation of opioid receptors (ORs) beyond the targeted tissue can cause dysphoria, pruritus, and constipation. Therefore, selective activation of peripheral ORs present in the afferent fibers of the targeted tissue can be considered a superior strategy in opioid analgesia to avoid potential adverse effects. The purpose of this study was to clarify the role of peripheral kappa opioid receptors (kORs) in arthritic pain for the possible use of peripheral ORs as a target in anti-nociceptive therapy. We administered U50488 or nor-BNI/DIPPA, a selective agonist or antagonist of kOR, respectively into arthritic rat knee joints induced using 1% carrageenan. After the injection of U50488 or U50488 with nor-BNI or DIPPA into the inflamed knee joint, we evaluated nociceptive behavior as indicated by reduced weight-bearing on the ipsilateral limbs of the rat and recorded the activity of mechanosensitive afferents (MSA). In the inflamed knee joint, the intra-articular application of 1MUM, 10nM, or 0.1nM U50488 resulted in a significant reduction in nociceptive behavior. In addition, 1MUM and 10nM U50488 decreased MSA activity. However, in a non-inflamed knee joint, 1MUM U50488 had no effect on MSA activity. Additionally, intra-articular pretreatment with 20MUM nor-BNI or 10MUM DIPPA significantly blocked the inhibitory effects of 1MUM U50488 on nociceptive behavior and MSA activity in the inflamed knee joint. These results implicate that peripheral kORs can contribute to anti-nociceptive processing in an inflamed knee joint. PMID- 27378585 TI - Group 2 Pulmonary Hypertension Special Issue. PMID- 27378584 TI - Co-expression of GAD67 and choline acetyltransferase in neurons in the mouse spinal cord: A focus on lamina X. AB - Lamina X of the spinal cord is a functionally diverse area with roles in locomotion, autonomic control and processing of mechano and nociceptive information. It is also a neurochemically diverse region. However, the different populations of cells in lamina X remain to be fully characterised. To determine the co-localisation of the enzymes responsible for the production of GABA and acetylcholine (which play major roles in the spinal cord) in lamina X of the adult and juvenile mouse, we used a transgenic mouse expressing green fluorescent protein (GFP) in glutamate decarboxylase 67 (GAD67) neurons, combined with choline acetyltransferase (ChAT) immunohistochemistry. ChAT-immunoreactive (IR) and GAD67-GFP containing neurons were observed in lamina X of both adult and juvenile mice and in both age groups a population of cells containing both ChAT IR and GAD67-GFP were observed in lumbar, thoracic and cervical spinal cord. Such dual labelled cells were predominantly located ventral to the central canal. Immunohistochemistry for vesicular acetylcholine transporter (VAChT) and GAD67 revealed a small number of double labelled terminals located lateral, dorsolateral and ventrolateral to the central canal. This study therefore describes in detail a population of ChAT-IR/GAD67-GFP neurons predominantly ventral to the central canal of the cervical, thoracic and lumbar spinal cord of adult and juvenile mice. These cells potentially correspond to a sub-population of the cholinergic central canal cluster cells which may play a unique role in controlling spinal cord circuitry. PMID- 27378586 TI - Dermoscopy and direct immunofluorescence findings of elastosis perforans serpiginosa. AB - Elastosis perforans serpiginosa (EPS) is a rare skin disorder characterized by transepidermal elimination of abnormal elastic fibres. We present a new case of D penicillamine (DPA)-induced EPS, and describe the clinical, dermoscopic, histopathological and direct immunofluorescence (DIF) findings. A 33-year-old woman receiving treatment with DPA presented with annular skin lesions. Digital dermoscopy of the lesions showed a central area of pink and yellowish discolouration with keratotic papules in the periphery, surrounded by a white halo, disposed in a way that resembled the islands of an archipelago. Other lesions showed a white to yellow central colouration and 'chrysalides' surrounding the keratotic plugs. Linear and granular deposits of IgG attached to the abnormal elastic fibres were seen with DIF. Dermoscopy can be helpful in the diagnosis of EPS. Moreover, DIF findings in skin biopsies of this case support the immune-mediated pathogenesis of EPS. PMID- 27378588 TI - Highly efficient adenoviral transduction of pancreatic islets using a microfluidic device. AB - Tissues are challenging to genetically manipulate due to limited penetration of viral particles resulting in low transduction efficiency. We are particularly interested in expressing genetically-encoded sensors in ex vivo pancreatic islets to measure glucose-stimulated metabolism, however poor viral penetration biases these measurements to only a subset of cells at the periphery. To increase mass transfer of viral particles, we designed a microfluidic device that holds islets in parallel hydrodynamic traps connected by an expanding by-pass channel. We modeled viral particle flow into the tissue using fluorescently-labelled gold nanoparticles of varying sizes and showed a penetration threshold of only ~5 nm. To increase this threshold, we used EDTA to transiently reduce cell-cell adhesion and expand intercellular space. Ultimately, a combination of media flow and ETDA treatment significantly increased adenoviral transduction to the core of the islet. As proof-of-principle, we used this protocol to transduce an ER-targeted redox sensitive sensor (eroGFP), and revealed significantly greater ER redox capacity at core islet cells. Overall, these data demonstrate a robust method to enhance transduction efficiency of islets, and potentially other tissues, by using a combination of microfluidic flow and transient tissue expansion. PMID- 27378587 TI - Long length of hospital stay in children with medical complexity. AB - BACKGROUND: Hospitalizations of children with medical complexity (CMC) account for one-half of hospital days in children, with lengths of stays (LOS) that are typically longer than those for children without medical complexity. The objective was to assess the impact of, risk factors for, and variation across children's hospitals regarding long LOS (>=10 days) hospitalizations in CMC. METHODS: A retrospective study of 954,018 CMC hospitalizations, excluding admissions for neonatal and cancer care, during 2013 to 2014 in 44 children's hospitals. CMC were identified using 3M's Clinical Risk Group categories 6, 7, and 9, representing children with multiple and/or catastrophic chronic conditions. Multivariable regression was used to identify demographic and clinical characteristics associated with LOS >=10 days. Hospital-level risk adjusted rates of long LOS generated from these models were compared using a covariance test of the hospitals' random effect. RESULTS: Among CMC, LOS >=10 days accounted for 14.9% (n = 142,082) of all admissions and 61.8% ($13.7 billion) of hospital costs. The characteristics most strongly associated with LOS >=10 days were use of intensive care unit (ICU) (odds ratio [OR]: 3.5, 95% confidence interval [CI]: 3.4-3.5), respiratory complex chronic condition (OR: 2.7, 95% CI: 2.6-2.7), and transfer from another medical facility (OR: 2.1, 95% CI: 2.0-2.1). After adjusting for severity, there was significant (P < 0.001) variation in the prevalence of LOS >=10 days for CMC across children's hospitals (range, 10.3%-21.8%). CONCLUSIONS: Long hospitalizations for CMC are costly. Their prevalence varies significantly by type of chronic condition and across children's hospitals. Efforts to reduce hospital costs in CMC might benefit from a focus on prolonged LOS. Journal of Hospital Medicine 2016;11:750-756. (c) 2016 Society of Hospital Medicine. PMID- 27378589 TI - Minimally Invasive Transradial Percutaneous Closure of Aortic Paravalvular Leaks: Following the Steps of Percutaneous Coronary Intervention. AB - Two patients with severe aortic paravalvular leaks (PVLs) in a mechanical prosthesis were percutaneously treated. Procedures were performed with mild sedation, angiographic guidance, and a 6-French right radial artery approach with good final results. Percutaneous PVL treatment is routinely performed with general anaesthesia, transesophageal echocardiographic guidance, and femoral access. Although another case of radial aortic PVL closure has been previously reported, it was performed with an 8-French radial sheath, transesophageal echocardiographic guidance, and general anaesthesia. According to our initial experience, aortic PVLs could be treated in a minimally invasive way. Larger studies should be conducted to confirm these observations. PMID- 27378590 TI - Aortitis With Associated Left Main Coronary Artery Stenosis: Role of Cardiac Computed Tomography. AB - We report on a 49-year-old man who presented to the emergency department with progressive angina. Echocardiography displayed severe aortic regurgitation and aortic valve thickening. The suspected diagnosis was acute aortic syndrome. Cardiac computed tomography showed circumferential thickening of the aortic wall and left main coronary artery ostial stenosis. Histologic examination showed diffuse aortic inflammation. No damage of any other organ or vascular structure was reported, and the final diagnosis was nonspecific aortitis. Differential diagnosis, prognosis, and therapeutic strategies are discussed. PMID- 27378592 TI - Combination Therapy for Pulmonary Arterial Hypertension: A Systematic Review and Meta-analysis. AB - BACKGROUND: Combination therapy (CT) for patients with pulmonary arterial hypertension (PAH) has been recommended for many years, despite weak evidence of efficacy over monotherapy (MT). A previous meta-analysis comparing CT vs MT with pulmonary vasodilators failed to demonstrate a clear reduction in clinical worsening events. METHODS: We searched for relevant articles in PubMed, EMBASE, the Cochrane Database, and clinicaltrials.gov; we also manually searched review articles and conference abstracts from 1980-December 2015. Target articles were double-blinded studies of 2 or more pulmonary vasodilators given in combination vs monotherapy for treatment of patients with PAH. The principal outcome of interest was "combined clinical worsening" (CCW) events (including but not limited to death or hospitalization). Data on physiological outcomes were also explored. Meta-analysis was performed using the DerSimonian and Laird random effects model. RESULTS: We extracted data from 18 randomized controlled trials (RCTs) (N = 4162). CT was associated with a significant 38% reduction of risk of CCW (15 RCTs: n = 3906; risk ratio [RR], 0.62; 95% confidence interval [CI], 0.50 0.77). This reduction in risk was driven by a reduction in nonfatal end points (12 RCTs: n = 2611; RR, 0.56; 95% CI, 0.40-0.78) and not by a reduction of mortality (12 RCTs: n = 2717; RR, 0.79; 95% CI, 0.53-1.17). CT was also associated with improvement in 6-minute walking distance (10 RCTs: n = 1553; weighted mean difference [WMD], +23.0 m; 95% CI, 15.9-30.1), improved functional class (9 RCTs: n = 1737; RR, 1.26; 95% CI, 1.05-1.51), and beneficial effects on pulmonary hemodynamics such as cardiac index (WMD, +0.35 L/min/m; 95% CI, 0.14 0.56). CONCLUSIONS: In this highly comprehensive meta-analysis, CT reduces the risk of CCW events in patients with PAH and brings physiological improvement. PMID- 27378591 TI - Patient-Centred Care of Older Adults With Cardiovascular Disease and Multiple Chronic Conditions. AB - Multimorbidity, defined as the presence of 2 or more chronic conditions, is common among older adults with cardiovascular disease. These individuals are at increased risk for poor health outcomes and account for a large proportion of health care utilization. Clinicians are challenged with the heterogeneity of this population, the complexity of the treatment regimen, limited high-quality evidence, and fragmented health care systems. Each treatment recommended by a clinical practice guideline for a single cardiovascular disease might be rational, but the combination of all evidence-based recommendations can be impractical or even harmful to individuals with multimorbidity. These challenges can be overcome with a patient-centred approach that incorporates the individual's preferences, relevant evidence, the overall and condition-specific prognosis, clinical feasibility of treatments, and interactions with other treatments and coexisting chronic conditions. The ultimate goal is to maximize benefits and minimize harms by optimizing adherence to the most essential treatments, while acknowledging trade-offs between treatments for different health conditions. It might be necessary to discontinue therapies that are not essential or potentially harmful to decrease the risk of drug-drug and drug disease interactions from polypharmacy. A decision to initiate, withhold, or stop a treatment should be on the basis of the time horizon to benefits vs the individual's prognosis. In this review, we illustrate how cardiologists and general practitioners can adopt a patient-centred approach to focus on the aspects of cardiovascular and noncardiovascular health that have the greatest effect on functioning and quality of life in older adults with cardiovascular disease and multimorbidity. PMID- 27378593 TI - NF-kappaB-Dependent Upregulation of NCX1 Induced by Angiotensin II Contributes to Calcium Influx in Rat Aortic Smooth Muscle Cells. AB - BACKGROUND: The reverse mode of Na+/Ca2+ exchanger (NCX) 1 can transport Ca2+ into cells and is involved in the contractile regulation of vascular smooth muscle cells (VSMCs) and the development of hypertension. We hypothesized that upregulation of NCX1 expression induced by angiotensin II (Ang II) could be dependent on activation of nuclear factor-kappa B (NF-kappaB) and contributes to Ca2+ influx in VSMCs. METHODS: An osmotic minipump was implanted for administration of Ang II in Sprague-Dawley rats, and blood pressure, as well as NCX1 expression, in the aorta was measured. VSMCs were cultured to verify that Ang II-upregulated NCX1 expression is dependent on activation of NF-kappaB and contributes to Ca2+ influx. RESULTS: Ang II-upregulated NCX1 expression in rat aortas (2.1-fold at day 6) and VSMCs (1.7-fold at 24 hours) and NF-kappaB knockdown and p38 mitogen-activated protein kinase (MAPK) inhibitor resulted in 2.1- and 2.0-fold decreases in Ang II-upregulated NCX1 expression in VSMCs. KB R7943 (an inhibitor of NCX1 reversal) and NCX1 knockdown decreased Ang II-induced Ca2+ influx 1.4- and 1.3- fold, respectively. KB-R7943 and removal of extracellular Na+ decreased Ang II-initiated store depletion-mediated Ca2+ entry by 1.5- and 1.3-fold, respectively. Moreover, NF-kappaB knockdown and use of a p38 MAPK inhibitor resulted in about 1.3-fold decreases in Ang II-induced Ca2+ influx through activation of reverse-mode NCX1. CONCLUSIONS: Ang II upregulates NCX1 expression through p38 MAPK and NF-kappaB pathways, and reverse-mode NCX1 plays an important part in Ang II-induced Ca2+ influx in VSMCs, which may be associated with Ang II-initiated store-operated channel entry. PMID- 27378594 TI - Complete vs Culprit-Only Percutaneous Coronary Intervention in STEMI With Multivessel Disease: A Meta-analysis and Trial Sequential Analysis of Randomized Trials. AB - BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) and multivessel disease (MVD) most commonly are treated with culprit-only percutaneous coronary intervention (PCI). However, this has been recently challenged, suggesting benefit with complete revascularization (CR). Still, these latest findings are largely based on clinical trials powered for composite outcomes that frequently include "softer" end points. We performed a meta analysis comparing routine culprit-only PCI vs CR in STEMI, with an emphasis on "hard" clinical end points. METHODS: MEDLINE, EMBASE, ISI Web of Science, and CENTRAL were searched from 1996-May 2015. Studies included patients with STEMI and MVD who received primary PCI. The primary end point was long-term death/myocardial infarction (MI). Data were combined using a fixed-effects model. RESULTS: Seven randomized trials (2004 patients: 1065 CR and 939 culprit-only PCI procedures) were included. Compared with culprit-only PCI, CR reduced the composite of death/MI (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.52 0.96) but not death (OR, 0.78; 95% CI, 0.53-1.15) or recurrent MI (OR, 0.85; 95% CI, 0.58-1.24) alone. If CR was performed during the index catheterization, a reduction in death/MI was observed (death/MI: OR, 0.41; 95% CI, 0.25-0.65; death: OR, 0.59; 95% CI, 0.34-1.00; recurrent MI: OR, 0.35; 95% CI, 0.18-0.69). If staged, no benefits were noted (death/MI: OR, 0.99; 95% CI, 0.67-1.45; death: OR, 0.95; 95% CI, 0.56-1.61; recurrent MI: OR, 1.02; 95% CI, 0.61-1.70). However, when trial sequential analysis was performed for the overall population, the cumulative z-curve did not cross the monitoring boundary, suggesting a lack of evidence for reducing death/MI with CR (similar for index catheterization). CONCLUSIONS: In STEMI with MVD, there is insufficient evidence to support a reduction in death/MI with CR. Our results reinforce the need for larger clinical trials powered for robust clinical end points. PMID- 27378595 TI - Lack of Association Between Extracranial Carotid and Vertebral Artery Disease and Stroke After Transcatheter Aortic Valve Replacement. AB - BACKGROUND: Carotid artery stenosis is a risk factor for stroke after surgical aortic valve replacement, but it is unknown whether carotid and vertebral artery disease impacts the risk of stroke after transcatheter aortic valve replacement (TAVR). METHODS: We reviewed 294 consecutive cases of TAVR at a tertiary care medical centre. Thirty-one patients without preoperative carotid/vertebral duplex ultrasonograms were excluded. Carotid or vertebral artery disease was defined on the basis of >50% stenosis. Outcomes were stroke within 30 days after TAVR, 30 day mortality, and overall survival. RESULTS: Fifty-one patients (19%) had at least 50% stenosis of a carotid or vertebral artery. The carotid and vertebral artery disease group had higher rates of coronary artery disease, previous coronary artery bypass surgery, and peripheral artery disease compared with the control group. Transfemoral access was less common in the carotid and vertebral artery disease group (55% vs 77%; P < 0.01). Stroke occurred in 6.8% of patients (n = 18) within 30 days after TAVR, but no patients in the carotid and vertebral artery disease group had a stroke. The presence of at least 50% stenosis of a carotid or vertebral artery was not predictive of stroke by logistic regression. There was no difference in 30-day mortality (10% vs 4%; P = 0.11) and overall survival (log-rank test P = 0.84) between the groups. CONCLUSIONS: The presence or absence of carotid or vertebral artery stenosis was not significantly related to the occurrence of stroke after TAVR. Routine screening for carotid and vertebral artery disease before TAVR does not appear justified. PMID- 27378596 TI - Predictors of Ventricular Arrhythmias and Sudden Death in a Quebec Cohort With Brugada Syndrome. AB - BACKGROUND: Patients with Brugada syndrome (BrS) are at risk for ventricular arrhythmias (VAs) and sudden death. Identification of high-risk individuals beyond those with syncope or resuscitated sudden death remains a major challenge. METHODS: We assessed the value of clinical, electrophysiological, and electrocardiographic (ECG) features, including depolarization and repolarization metrics, in predicting arrhythmic events and sudden death in consecutive patients with BrS diagnosed between 2002 and 2013 in Quebec, Canada. Qualifying electrocardiograms with the highest type 1 ST-segment elevations were reviewed and analyzed by 2 electrophysiologists who were blinded to clinical history. Survival analyses were adjusted for Firth bias correction and left truncation. RESULTS: A total of 105 patients, 79.8% of whom were men, were diagnosed with BrS at a mean age of 46.2 +/- 13.3 years and were followed for 59.6 +/- 16.4 months. Ten (9.5%) had a history of cardiac arrest, 37 (35.2%) had syncope, and 7 (6.7%) experienced 20 arrhythmic events during follow-up, all consisting of appropriate ICD therapy (7 antitachycardia pacing; 13 shocks). In multivariate Cox regression analyses, a spontaneous type 1 electrocardiographic (ECG) pattern (hazard ratio [HR], 10.80; 95% confidence interval [CI], 1.03-113.87; P = 0.0476), maximal T peak-end (Tp-e) duration >= 100 ms (HR, 29.73; 95% CI, 1.33-666.37; P = 0.0325), and QRS duration in lead V6 > 110 ms (HR, 15.27; 95% CI, 1.07-217.42; P = 0.0443) were independently associated with VAs or aborted sudden cardiac death. CONCLUSIONS: In a multicentre cohort with BrS from Quebec, Canada, VAs and sudden death were independently associated with standard 12-lead ECG features, including a spontaneous type 1 pattern, depolarization (QRS in lead V6), and repolarization (maximal Tp-e duration) criteria. PMID- 27378597 TI - Spin diffusion and non-local spin-valve effect in an exfoliated multilayer graphene with a Co electrode. AB - We fabricated a non-local spin valve with a thin layer of graphite with Co transparent electrodes. The spin-valve effect and spin precession were observed at room temperature. The magnitude of the mangetoresistance increases when temperature decreases. The spin-relaxation time, [Formula: see text], obtained from the fitting of the Hanle curves increases with decreasing temperature with a weak dependence [Formula: see text] while the spin-diffusion constant D decreases. At room temperature, [Formula: see text] exceeds 100 ps and the spin diffusion length, [Formula: see text], is ~2 MUm. The temperature dependence of [Formula: see text] is not monotonic, and it has the largest value at room temperature. Our results show that multilayer graphene is a suitable material for spintronic devices. PMID- 27378599 TI - An Azaacene Derivative as Promising Electron-Transport Layer for Inverted Perovskite Solar Cells. AB - It is highly desirable to develop novel n-type organic small molecules as an efficient electron-transport layer (ETL) for the replacement of PCBM to obtain high-performance metal-oxide-free, solution-processed inverted perovskite solar cells (PSCs) because this type of solar cells with a low-temperature and solution based process would make their fabrication more feasible and practical. In this research, the new azaacene QCAPZ has been synthesized and employed as non fullerene ETL material for inverted PSCs through a solution-based process without the need for additional dopants or additives. The as-fabricated inverted PSCs show a power conversion efficiency up to 10.26 %. Our results clearly suggest that larger azaacenes could be promising electron-transport materials to achieve high-performance solution-processed inverted PSCs. PMID- 27378598 TI - FOXN1 in thymus organogenesis and development. AB - Development of the primary T-cell repertoire takes place in the thymus. The linked processes of T-cell differentiation and T-cell repertoire selection each depend on interactions between thymocytes and thymic stromal cells; in particular, with the epithelial cells of the cortical and medullary thymic compartments (cortical and medullary thymic epithelial cells; cTECs and mTECs, respectively). The importance of the thymic epithelial cell lineage in these processes was revealed in part through analysis of nude (nu/nu) mice, which are congenitally hairless and athymic. The nude phenotype results from null mutation of the forkhead transcription factor FOXN1, which has emerged as a pivotal regulator both of thymus development and homeostasis. FOXN1 has been shown to play critical roles in thymus development, function, maintenance, and even regeneration, which positions it as a master regulator of thymic epithelial cell (TEC) differentiation. In this review, we discuss current understanding of the regulation and functions of FOXN1 throughout thymus ontogeny, from the earliest stages of organogenesis through homeostasis to age-related involution, contextualising its significance through reference to other members of the wider Forkhead family. PMID- 27378600 TI - Zinc Resistance Mechanisms of P1B-type ATPases in Sinorhizobium meliloti CCNWSX0020. AB - The Sinorhizobium meliloti (S. meliloti) strain CCNWSX0020 displayed tolerance to high levels exposures of multiple metals and growth promotion of legume plants grown in metal-contaminated soil. However, the mechanism of metal-resistant strain remains unknown. We used five P1B-ATPases deletions by designating as ?copA1b, ?fixI1, ?copA3, ?zntA and ?nia, respectively to investigate the role of P1B-ATPases in heavy metal resistance of S. meliloti. The ?copA1b and ?zntA mutants were sensitive to zinc (Zn), cadmium (Cd) and lead (Pb) in different degree, whereas the other mutants had no significant influence on the metal resistance. Moreover, the expression of zntA was induced by Zn, Cd and Pb whereas copA1b was induced by copper (Cu) and silver (Ag). This two deletions could led to the increased intracellular concentrations of Zn, Pb and Cd, but not of Cu. Complementation of ?copA1b and ?zntA mutants showed a restoration of tolerance to Zn, Cd and Pb to a certain extent. Taken together, the results suggest an important role of copA1b and zntA in Zn homeostasis and Cd and Pb detoxification in S. meliloti CCNWSX0020. PMID- 27378601 TI - Dose adjusted-EPOCH-R and mediastinal disease may improve outcomes for patients with gray-zone lymphoma. PMID- 27378602 TI - Audit of CT reporting standards in cases of intracerebral haemorrhage at a comprehensive stroke centre in Australia. AB - INTRODUCTION: Multiple CT-derived biomarkers that are predictive of intracerebral haemorrhage (ICH) growth and outcome have been described in the literature, but the extent to which these appear in imaging reports of ICH is unknown. The aim of this retrospective process audit was to determine which of the known predictors of ICH outcome was recorded in reports of the disease, with a view to providing reporting recommendations, as appropriate. METHOD: We examined the initial CT report of patients diagnosed with ICH presenting to a metropolitan comprehensive stroke centre and meeting inclusion criteria during the audit period between 1 March 2013 and 28 February 2014. Each report was assessed for the inclusion of the following ICH characteristics: the number of measurement dimensions; volume; location; hydrocephalus; shape; density; 'CTA spot sign' (where CTA was performed). RESULTS: A total of 100 patients met audit inclusion criteria. At least one ICH dimension was recorded in 90% of reports; however, 39% did not include the measurements in three dimensions and volume was reported in just 6%. No ICH dimension was recorded in 10% of reports. With the exception of density and shape, reporting of other CT features exceeded 95%. Where CTA was performed (58%), 14 (24%) of 58 reported the 'CTA spot sign' status. CONCLUSION: In this audit, volume was the most under-reported of the established ICH characteristics predictive of ICH outcome. Readily calculated from multiplanar reformats using the ABC/2 technique, the routine reporting of ICH volume is recommended. More reporting attention to ICH density heterogeneity and shape irregularity is encouraged, given their emerging importance. Where acute CTA is performed, the presence of any dynamic haemorrhage (CTA spot sign) should be reported. PMID- 27378603 TI - Protamine (heparin)-induced thrombocytopenia: a review of the serological and clinical features associated with anti-protamine/heparin antibodies. AB - Protamine is widely used in medicine as a rapidly-acting antidote to heparin, particularly for reversing heparin anticoagulation after cardiac surgery. Protamine is also used as a stabilizing additive to certain preparations of insulin. Recent reports demonstrate that protamine and heparin form multimolecular complexes that result in high rates of immunization in post cardiac surgery patients, particularly of immunoglobulin G (IgG) class antibodies; a subset of these anti-protamine/heparin IgG antibodies activates platelets through their FcgammaIIA (IgG) receptors. Although the clinical consequences of anti-protamine/heparin antibodies that are newly generated after cardiac surgery are unknown, there is evidence that platelet-activating anti protamine/heparin antibodies already present at the time of cardiac surgery might occasionally explain more severe thrombocytopenia with delayed platelet count recovery, as well as thromboembolic complications, in the post-cardiac surgery setting. Triggers for such antibodies remain poorly-defined, but could include preoperative administration of heparin to diabetic patients receiving protamine insulin as well as recent previous cardiac surgery. Anti-protamine/heparin antibodies have several features in common with anti-platelet factor 4 (PF4) PF4/heparin antibodies implicated in heparin-induced thrombocytopenia (HIT), including immunization by heparin-containing multimolecular complexes, predominant IgG class, pathological platelet-activating properties, relatively rapid IgG formation without IgM precedence, and antibody transience. Despite these similarities, the risk of anti-protamine/heparin antibody-mediated complications seems to affect the early post-cardiac surgery period, whereas HIT usually occurs at least 5 days following cardiac surgery. Clinicians need to become aware of this recently recognized immunohematological disorder, and research is needed to identify triggers of immunization, improve detection of pathological antibodies and identify patients at risk of this complication. PMID- 27378604 TI - Interventional cardiology, where real life and science do not necessarily meet. AB - Evidence-based diagnosis, decision-making, and therapy appear a must these days. Generating and publishing evidence is a tedious job according to ever new and tightened research practice regulations. Rules will never prevent the typical human behaviour from showing the new thing to be shinier and the old thing dustier than they really are. The medical community is solicited to concoct a meal that is gullible for patients, authorities, and third-party payers out of the available evidence (after applying some conversion factors correcting the common bias of the researchers), anticipation of what will be the evidence tomorrow, common sense, and digested experience. Examples of misguidance by poorly produced or misinterpreted evidence are plentiful in interventional cardiology as they are in other disciplines. Coronary stents, for instance, were first underestimated due to the fact that they were generally used in bailout situations where the outcome remained rather dismal in spite of the salvaging potential of stents. Then they were overused quite uncritically rather to the detriment of the patient. Now with the high quality of the modern drug-eluting stents (DESs), the overuse persists but is no longer a concern. However, the enhanced potential of DESs compared with bare-metal stents was poorly exploited for >10 years because of reports that slipped through the meshes of good review and publication practice to convey the untenable message that bare-metal stents were preferable in many situations. As other examples, use of the fractional flow reserve (FFR) for decision-making has to be questioned despite prominently published reports recommending it. Fixing a lesion is today easier and hardly more complication prone than assessing it with the FFR. Closure of the patent foramen ovale may never be properly applied, because the collection of the understandably requested evidence takes decades, a follow-up duration that makes research unattractive to physicians and financiers. Transarterial aortic valve replacement, finally, is certain to eventually supplant surgical aortic valve replacement. However, this should have already been accomplished as a logical progress. The adoption of this remarkable breakthrough technology is slowed down by the quest for providing randomized evidence in patients, for whom the evidence should rather be derived from already existing studies, and by the quest to triage all these patients in a heart team, meaning to also keep the surgeons happy, although these patients do not really need them. PMID- 27378606 TI - Four new HLA class I alleles in Spaniards, HLA-A*32:01:23, HLA-B*18:01:24, HLA B*18:72:02 and HLA-C*12:166. AB - Characterization of four new human leukocyte antigen (HLA) class I alleles, A*32:01:23, B*18:01:24, B*18:72:02 and C*12:166. PMID- 27378605 TI - Silica-coated magnetic nanoparticles impair proteasome activity and increase the formation of cytoplasmic inclusion bodies in vitro. AB - The potential toxicity of nanoparticles, particularly to neurons, is a major concern. In this study, we assessed the cytotoxicity of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye (MNPs@SiO2(RITC)) in HEK293 cells, SH-SY5Y cells, and rat primary cortical and dopaminergic neurons. In cells treated with 1.0 MUg/MUl MNPs@SiO2(RITC), the expression of several genes related to the proteasome pathway was altered, and proteasome activity was significantly reduced, compared with control and with 0.1 MUg/MUl MNPs@SiO2(RITC) treated cells. Due to the reduction of proteasome activity, formation of cytoplasmic inclusions increased significantly in HEK293 cells over-expressing the alpha-synuclein interacting protein synphilin-1 as well as in primary cortical and dopaminergic neurons. Primary neurons, particularly dopaminergic neurons, were more vulnerable to MNPs@SiO2(RITC) than SH-SY5Y cells. Cellular polyamines, which are associated with protein aggregation, were significantly altered in SH-SY5Y cells treated with MNPs@SiO2(RITC). These findings highlight the mechanisms of neurotoxicity incurred by nanoparticles. PMID- 27378608 TI - Immunoglobulin G fragment C receptor polymorphisms and efficacy of preoperative chemotherapy plus trastuzumab and lapatinib in HER2-positive breast cancer. AB - Lapatinib enhances antibody-dependent cell-mediated cytotoxicity (ADCC) activity of trastuzumab. FcgammaR polymorphisms have been associated with both ADCC and clinical activity of trastuzumab in HER2+ breast cancer (BC) patients (pts). We analyzed FcgammaRIIa-H131R and FcgammaRIIIa-V158F polymorphisms in the CHER-LOB trial population of HER2+ BCs treated with preoperative chemotherapy plus trastuzumab (arm A), lapatinib (arm B) or both (arm C). Genotyping was successfully performed in 73/121 (60%) pts. A significant improvement in pathological complete response (pCR) rate was observed for the combination arm C, but only in FcgammaRIIIa V allele carriers (C vs A, 67 vs 27%, P=0.043; C vs B, 67 vs 22%, P=0.012). An independent interaction between arm C and FcgammaRIIIa V allele was found for pCR (odds ratio=9.4; 95% confidence interval, 2.3-39.6; P=0.003). No significant associations were observed between pCR and FcgammaRIIa polymorphism, and between pre-treatment tumor-infiltrating lymphocytes and FcgammaR polymorphisms. Our study provides evidence for a FcgammaRIIIa V allele restricted pCR benefit from neoadjuvant trastuzumab plus lapatinib in HER2+ BC. PMID- 27378610 TI - Negative Poisson's Ratio in Modern Functional Materials. AB - Materials with negative Poisson's ratio attract considerable attention due to their underlying intriguing physical properties and numerous promising applications, particularly in stringent environments such as aerospace and defense areas, because of their unconventional mechanical enhancements. Recent progress in materials with a negative Poisson's ratio are reviewed here, with the current state of research regarding both theory and experiment. The inter relationship between the underlying structure and a negative Poisson's ratio is discussed in functional materials, including macroscopic bulk, low-dimensional nanoscale particles, films, sheets, or tubes. The coexistence and correlations with other negative indexes (such as negative compressibility and negative thermal expansion) are also addressed. Finally, open questions and future research opportunities are proposed for functional materials with negative Poisson's ratios. PMID- 27378609 TI - Effect of ABCB1 diplotype on tacrolimus disposition in renal recipients depends on CYP3A5 and CYP3A4 genotype. AB - The relevance of most genetic polymorphisms beyond CYP3A5*1 on tacrolimus disposition remains unclear. We constructed a predictive mixed model for tacrolimus dose-corrected trough concentration (C0/dose) at months 3, 12 and 24 after transplantation in a retrospective cohort of 766 predominantly Causasian adult renal recipients (n=2042 trough concentrations). All patients were genotyped for 32 single-nucleotide polymorphisms with a proven or possible relevance to tacrolimus disposition based on the previous studies. Of these, ABCB1, ABCC2, OATP1B1, COMT, FMO, PPARA and APOA5 were analyzed as (functional) diplotype groups. Predictors of C0/dose were CYP3A5*1, hematocrit, age, CYP3A4*22, use of concomitant CYP3A4 inhibitor or inducer, ALT, estimated glomerular filtration rate, tacrolimus formulation (once vs twice daily), ABCB1 diplotype and time after transplantation. The effect of ABCB1 diplotype was small but strongly accentuated in CYP3A4*22 carriers and non-existent in CYP3A5 expressors. ABCC2 diplotype had a limited effect on C0/dose that was only statistically significant in CYP3A5 non-expressors. PMID- 27378611 TI - A Health at Every Size intervention improves intuitive eating and diet quality in Canadian women. AB - BACKGROUND & AIMS: Health at Every Size(r) (HAES(r)) interventions focus on healthy lifestyle by promoting behavioral changes related to diet and physical activity while emphasizing self-acceptance and well-being through an empowerment and intuitive approach. The purpose of this study was to investigate the effects of a HAES(r) program on intuitive eating and diet quality in women. METHODS: The HAES(r) intervention, offered by professionals from Health and Social Services Centers in Quebec (Canada), was composed of thirteen 3-h weekly meetings and a 6 h intensive day. For this study, 216 women (1.9% normal-weight, 21.1% overweight, 77.0% obese) who took part to the HAES program were compared to 110 women (3.9% normal-weight, 23.3% overweight, 72.8% obese) from a control group (waiting list). Intuitive eating was assessed using the Intuitive Eating Scale and diet quality was evaluated through the calculation of the Healthy Eating Index (HEI) from a validated web-based self-administrated food frequency questionnaire. Measurements were performed at baseline, post-intervention, and at one-year follow-up. RESULTS: Women who participated in the HAES(r) program significantly increased their intuitive eating score compared to women in the control group at post-intervention and at follow-up (group by time interaction, p = 0.0002). A significant improvement in diet quality was also observed in the HAES(r) group in comparison with the control group at post-intervention (group by time interaction, p = 0.0139). The intuitive eating score and the HEI score were positively associated in the HAES(r) group at post-intervention (r = 0.20, p = 0.0237) and one-year follow-up (r = 0.22, p = 0.0359), but no such associations were noted in the control group (post-intervention, r = 0.04, p = 0.70; one-year follow-up, r = -0.15, p = 0.30). CONCLUSIONS: The HAES(r) program seems effective in improving intuitive eating and also favours improvements in diet quality. However, the association between intuitive eating and diet quality remains unclear, being positive and significant only after the HAES(r) intervention. PMID- 27378613 TI - Fluazifop- p-butyl, an aryloxyphenoxypropionate herbicide, diminishes renal and hepatic functions and triggers testicular oxidative stress in orally exposed rats. AB - Fluazifop- p-butyl (FPB) is a selective aryloxyphenoxypropionate herbicide. Its phytotoxicity mechanism involves inhibition of lipid biosynthesis, free-radical generation, and oxidative stress in vulnerable plants. This study evaluates the impact of orally administered FPB on selected tissues in non-target animal model. Twenty-four male wistar rats (160-180g) were randomized into groups (I-IV). Group I served as control, while animals in groups II, III, and IV received FPB at 18.75, 37.5, and 75 mg/kg body weight/day p.o., respectively, for 21 days. FPB caused significant ( p < 0.05) increase in plasma biomarkers of renal and hepatic function (urea, creatinine, bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase) when compared to control. Significant reductions in testicular ascorbic acid, glutathione, and activities of glutathione-S transferase, superoxide dismutase, and catalase were observed in FPB-treated animals when compared to control, in a dose-dependent manner. This was accompanied by increased testicular lipid peroxidation in the treated groups. Furthermore, a significant decrease in testicular acid phosphatase and gamma glutamyl transferase activities was also observed in the FPB-treated groups in a dose-dependent manner compared to control. However, testicular lactate dehydrogenase activity was significantly increased in the FPB-treated rats when compared to control. Additionally, histopathological studies revealed severe interstitial oedema and congestion of testicular blood vessels in the FPB-treated groups. Overall, data from this study suggest that FPB induced hepatotoxicity, nephrotoxicity, and oxidative stress-mediated alteration of testicular functions in rat. PMID- 27378612 TI - Culprit lesion location and outcome in patients with cardiogenic shock complicating myocardial infarction: a substudy of the IABP-SHOCK II-trial. AB - BACKGROUND: In myocardial infarction without cardiogenic shock (CS), the affected coronary vessel has significant influence on the final infarct size and patient prognosis. CS data on this relation are scarce. The objective of this study was to determine the prognostic relevance of the culprit lesion location in patients with CS complicating acute myocardial infarction. METHODS: In the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial patients with CS were randomized to therapy with intraaortic balloon pump or control. Additional CS patients not eligible for the randomized trial were included in a registry. We compared the location of the culprit lesions in these patients with regard to the affected coronary vessel [left main (LM), left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA)] and location within the vessel (proximal, mid or distal) regarding short- and long-term outcome. RESULTS: Of 758 patients, the majority had the culprit lesion in the LAD (44 %) compared to RCA (27 %), LCX (19 %) or LM (10 %). Proximal lesions were more frequent than mid or distal culprit lesions (60 vs. 27 vs. 13 %, p < 0.001). No differences were observed for mortality with respect to either culprit vessel (log-rank p value = 0.54). In contrast, a higher mortality was observed for patients with distal culprit lesions after 1 year (log-rank p value = 0.04). This difference persisted after multivariable adjustment (hazard ratio for distal lesions 1.40; 95 % confidential interval 1.03-1.90; p = 0.03). CONCLUSION: For patients with CS complicating myocardial infarction, the culprit vessel seems to be unrelated with mortality whereas distal culprit lesions may have a worse outcome. PMID- 27378614 TI - Introducing The Wiley Transplant Peer Review Network. PMID- 27378615 TI - Long-Term Hemodialysis via Arteriovenous Fistula in Patients With Continuous-Flow Left Ventricular Assist Devices. PMID- 27378616 TI - Communications. PMID- 27378617 TI - Effects of Nano-hydroxyapatite/Poly(DL-lactic-co-glycolic acid) Microsphere-Based Composite Scaffolds on Repair of Bone Defects: Evaluating the Role of Nano hydroxyapatite Content. AB - The aim of the current study was to prepare microsphere-based composite scaffolds made of nano-hydroxyapatite (nHA)/poly (DL-lactic-co-glycolic acid) (PLGA) at different ratios and evaluate the effects of nHA on the characteristics of scaffolds for tissue engineering application. First, microsphere-based composite scaffolds made of two ratios of nHA/PLGA (nHA/PLGA = 20/80 and nHA/PLGA = 50/50) were prepared. Then, the effects of nHA on the wettability, mechanical strength, and degradation of scaffolds were investigated. Second, the biocompatibility and osteoinductivity were evaluated and compared by co-culture of scaffolds with bone marrow stromal stem cells (BMSCs). The results showed that the adhesion, proliferation, and osteogenic differentiation of BMSCs with nHA/PLGA (50/50) were better than those with nHA/PLGA (20/80). Finally, we implanted the scaffolds into femur bone defects in a rabbit model, then the capacity of guiding bone regeneration as well as the in vivo degradation were observed by micro-CT and histological examinations. After 4 weeks' implantation, there was no significant difference on the repair of bone defects. However, after 8 and 12 weeks' implantation, the nHA/PLGA (20/80) exhibited better bone formation than nHA/PLGA (50/50). These results suggested that a proper concentration of nHA in the nHA/PLGA composite should be taken into account when the composite scaffolds were prepared, which plays an important role in the biocompatibility, degradation rate and osteoconductivity. PMID- 27378618 TI - Intermittent urethral catheterisation: the reality of the lubricants and catheters in the clinical practice of a Brazilian service. AB - AIMS AND OBJECTIVES: To identify how catheters and lubricants have been used among patients using intermittent urinary catheterisation in rehabilitation. BACKGROUND: The clean intermittent urinary catheterisation technique is an invasive procedure can cause discomfort, pain and urethral traumas. The use of lubricants and lubricated urinary catheters reduces the friction between the catheter and the urethral mucosa, minimising the risks. DESIGN: A descriptive exploratory design was used. METHODS: Quantitative and descriptive study developed at a rehabilitation centre of a University Hospital in the interior of the state of Sao Paulo, Brazil, at the Intermittent Urinary Catheterisation Outpatient Clinic, between June 2012-December 2014. After ethical approval, the data were collected through an interview with the support of a semistructured questionnaire, held during the nursing consultation. Among the users, patients using intermittent urinary catheterisation were interviewed, over 18 years of age and minors younger than eight years accompanied. Descriptive statistical analysis was applied. RESULTS: Most of 214 (100.0%) patients were interviewed were male, single, young adults and with a primary medical diagnosis of bone marrow injury and myelomeningocele. Most patients perform the urinary catheterisation between four and six times per day. For the procedure, the majority uses polyethylene (polyvinyl chloride) catheter and, as a lubricant, 2.0% lidocaine hydrochloride on the catheter itself. Many mention lack of sensitivity when passing the catheter. CONCLUSION: In the study sample, a risk of urethral traumas was evidenced, related to the inappropriate use of catheters and lubricants. For the patients' safety, the professionals need to acknowledge the importance of the appropriate use of lubricants and lubricated catheters to implement evidence based practices that mobilise public policies. RELEVANCE TO CLINICAL PRACTICE: The use of evidences demonstrates that the appropriate use of lubricants for intermittent urinary catheterisation is fundamental for patient safety and the performance of the best practices. PMID- 27378619 TI - Characterization and reconstruction of 3D stochastic microstructures via supervised learning. AB - The need for computational characterization and reconstruction of volumetric maps of stochastic microstructures for understanding the role of material structure in the processing-structure-property chain has been highlighted in the literature. Recently, a promising characterization and reconstruction approach has been developed where the essential idea is to convert the digitized microstructure image into an appropriate training dataset to learn the stochastic nature of the morphology by fitting a supervised learning model to the dataset. This compact model can subsequently be used to efficiently reconstruct as many statistically equivalent microstructure samples as desired. The goal of this paper is to build upon the developed approach in three major directions by: (1) extending the approach to characterize 3D stochastic microstructures and efficiently reconstruct 3D samples, (2) improving the performance of the approach by incorporating user-defined predictors into the supervised learning model, and (3) addressing potential computational issues by introducing a reduced model which can perform as effectively as the full model. We test the extended approach on three examples and show that the spatial dependencies, as evaluated via various measures, are well preserved in the reconstructed samples. PMID- 27378620 TI - Oil sands tailings ponds harbour a small core prokaryotic microbiome and diverse accessory communities. AB - Oil sands tailings ponds store the waste slurry generated by extracting bitumen from surface-mined oil (tar) sands ores. The ponds support diverse microbial communities involved in element cycling, greenhouse gas production, and hydrocarbon biodegradation that influence pond management and their environmental footprint. Since previous reports indicate that there are similar microbial metabolic functions amongst ponds, analogous microbiomes may be expected but ponds actually harbour distinct communities. Partial 16S rRNA gene pyrotag sequences from 95 samples were obtained from six ponds managed by three operators. From these we discerned a core prokaryotic microbiome, a subset of microbes shared amongst different samples, defined as operational taxonomic units (OTUs) at the lowest taxonomic level identifiable in individual ponds and pooled pond datatsets. Of the ~1500-2700 OTUs detected per pond, 4-10 OTUs were shared among >=75% of the samples per pond, but these few OTUs represented 39-54% of the ponds' sequence reads. Only 2-5 OTUs were shared by the majority of samples from all ponds. Thus the prokaryotic communities within these ponds consist of a few core taxa and numerous accessory members that likely afford resiliency and functional redundancy including roles in iron-, nitrogen- and sulfur-cycling, syntrophy, fermentation, and methanogenesis. PMID- 27378622 TI - Targeted supplementation design for improved production and quality of enveloped viral particles in insect cell-baculovirus expression system. AB - The recent approval of vaccines and gene therapy products for human use produced in the Insect Cell-Baculovirus Expression Vector System (IC-BEVS) underlines the high potential and versatility of this platform. The interest in developing robust production processes emerges to cope with manufacturing pressure, as well as stringent product quality guidelines. Previously, we addressed the impact of the baculovirus infection on the physiology of insect host cell lines, identifying key cellular pathways enrolled in heterologous gene/protein expression. In the present work, this knowledge was applied to design tailored media supplementation schemes to boost IC-BEVS production yields and quality of enveloped viral particles: influenza VLPs (Inf-VLP) and baculovirus vectors (BV). The addition of reduced glutathione, antioxidants and polyamines increased the cell specific yields of baculovirus particles up to 3 fold. Cholesterol was identified as the most critical system booster, capable of improving 2.5 and 6 fold cell specific yields of BV and Inf-VLPs, respectively. Surprisingly, the combination of polyamines and cholesterol supplementation improved baculovirus stock quality, by preventing the accumulation of non-infectious particles during viral replication while selectively increasing infectious particles production. In addition, the specific yields of both enveloped viral particles, BVs and Inf VLPs, were also increased. The correlation between supplement addition and systems productivity was extensively analyzed, providing a critical assessment on final product quantity and quality as drivers of bioprocess optimization efforts. PMID- 27378621 TI - Screening of recombinant glycosyltransferases reveals the broad acceptor specificity of stevia UGT-76G1. AB - UDP-glycosyltransferases (UGTs) are a promising class of biocatalysts that offer a sustainable alternative for chemical glycosylation of natural products. In this study, we aimed to characterize plant-derived UGTs from the GT-1 family with an emphasis on their acceptor promiscuity and their potential application in glycosylation processes. Recombinant expression in E. coli provided sufficient amounts of enzyme for the in-depth characterization of the salicylic acid UGT from Capsella rubella (UGT-SACr) and the stevia UGT from Stevia rebaudiana (UGT 76G1Sr). The latter was found to have a remarkably broad specificity with activities on a wide diversity of structures, from aliphatic and branched alcohols, over small phenolics to larger flavonoids, terpenoids and even higher glycoside compounds. As an example for its industrial potential, the glycosylation of curcumin was thoroughly evaluated. Under optimized conditions, 96% of curcumin was converted within 24h into the corresponding curcumin beta glycosides. In addition, the reaction was performed in a coupled system with sucrose synthase from Glycine max, to enable the cost-efficient (re)generation of UDP-Glc from sucrose as abundant and renewable resource. PMID- 27378623 TI - Effects of antiretroviral treatment on paraoxonase 1 (PON1) activity in rats. AB - Highly active antiretroviral therapy (HAART), especially protease inhibitors (PIs), commonly used in HIV-infected patients, effectively suppresses a viral replication. However, it is frequently associated with significant side effects, including fat redistribution, lipodystrophy, hyperlipidemia, insulin resistance and diabetes mellitus. Currently, metabolic complications and atherosclerosis resulting from them become the major cause of mortality in HIV-infected patients receiving HAART. Paraoxonase 1 (PON1) is the HDL-bound esterase, which inhibits development of atherosclerosis by decomposing lipid peroxidation products and hydrolyzing homocysteine thiolactone. The aim of this study was to characterize the effects of HIV protease inhibitors on PON1 activity, total plasma homocysteine and protein-bound homocysteine thiolactone as well as lipid profile in rats. The study was performed on seven groups of male Wistar rats: (1) control; (2) and (3) receiving ritonavir (RTV) at doses of 10 and 50 mg/kg, respectively; (4) and (5) receiving atazanavir (ATV) at 10 and 100 mg/kg, respectively; (6) and (7) receiving saquinavir (SQV) at 10 and 50 mg/kg, respectively. All drugs were administered orally for 4 weeks. Compared to control animals, rats receiving PIs had significantly higher concentration of triglycerides and total cholesterol, but the levels of HDL-cholesterol were not different between groups. PON1 activity toward paraoxon was decreased in groups receiving PIs (control: 149 +/- 5 U/ml; PIs-treated: RTV at doses 10 mg/kg 133 +/ 9.5 U/ml, RTV at doses 50 mg/kg 134 +/- 10.8 U/ml, SQV at doses 10 mg/kg 131 +/ 9.2 U/ml, ATV at doses 10 mg/kg 132 +/- 11.8 U/ml, ATV at doses 100 mg/kg 108 +/ 7.8 U/ml). ATV reduced total homocysteine level around 25-28%, whereas other PIs had no effect on its concentration. In contrast, 10-15% increase in protein-bound homocysteine thiolactone was observed in PIs-receiving groups, such as RTV10, RTV50, SQV50, ATV10. In conclusion, dyslipidemia induced by PIs is associated with reduced PON1 activity as well as increased protein homocysteinylation. PON1 deficiency may contribute to increased risk of atherosclerosis in these patients. PMID- 27378625 TI - Oxidative stress, polarization of macrophages and tumour angiogenesis: Efficacy of caffeic acid. AB - Macrophage polarization is a process when macrophage expresses different functional programs in response to microenvironmental signals and two extreme forms exist; M1 and M2 macrophages. M1 macrophages are highly microbicidal and anticancer with enhanced ability to kill and phagocytose pathogens, upregulate pro-inflammatory cytokines and reactive molecular species, and present antigens; M2 macrophages and the related tumour associated macrophages (TAMs) regulate tissue remodelling and promote tissue repair and angiogenesis and can amplification of metabolic pathways that can suppress adaptive immune responses. It is demonstrated that ROS production, critical for the activation and functions of M1 macrophages, is necessary for the differentiation of M2 macrophages and TAMs, and that antioxidant therapy blocks TAMs differentiation and tumorigenesis in mouse models of cancer. In order to study how caffeic acid (CA), a natural antioxidant, affects macrophage function, polarization, angiogenesis and tumour growth we injected mice with Ehrlich ascites tumour (EAT) cells and treated them for 10 days with CA in a dose of 40 and/or 80 mg kg(-1.) Macrophage polarization was further characterized by quantifying secreted pro- and anti-inflammatory cytokines, nitric oxide and arginase 1 activity. CA may increase the cytotoxic actions of M1 macrophages and inhibit tumour growth; inhibitory activity on TAMs may be mediated through its antioxidative activity. Taken together, we conclude that the antitumour activity of CA was the result of the synergistic activities of different mechanisms by which CA acts on proliferation, angiogenesis, immunomodulation and survival. The continuous administration of CA efficiently blocked the occurrence of TAMs and markedly suppressed tumorigenesis in mouse cancer models. Targeting TAMs by antioxidants can be a potentially effective method for cancer treatment. PMID- 27378624 TI - Selective inhibition of JAK2/STAT1 signaling and iNOS expression mediates the anti-inflammatory effects of coniferyl aldehyde. AB - Urgent needs still exist for selective control of excessive inflammation. Despite the therapeutic potential of natural compounds against inflammation-associated chronic conditions, lack of specific molecular targets renders these bioactive compounds difficult for further development. Here we examined the bioactivity of coniferyl aldehyde (CA), a natural phenolic compound found in several dietary substances and medicinal plants, elucidating its efficacy both in vivo and in vitro with underlying molecular mechanisms. IFN-gamma/TNF-alpha-stimulated human keratinocytes and lipopolysaccharide (LPS)-stimulated murine macrophages were used to examine the effect of CA in vitro and to elucidate the underlying mechanisms. In vivo models of phorbol 12-myristate 13-acetate (TPA)-induced ear edema and carrageenan (CRG)-induced paw edema were employed to investigate the topical and systemic anti-inflammatory effects of CA, respectively. CA significantly reduced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in LPS-stimulated macrophages. While nuclear factor kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPKs) pathways, the representative cellular pathways for iNOS induction, were not affected by CA, phosphorylation of Janus kinase 2 (JAK2) and signal Transducers and Activators of Transcription 1 (STAT1) and subsequent nuclear translocation of p-STAT1 were significantly decreased by CA. The effect of CA on JAK2-STAT1-iNOS axis was also observed in human keratinocytes stimulated with IFN-gamma/TNF-alpha. Topical application of CA to mice produced significant protection against TPA-induced ear edema along with suppressed epidermal hyperproliferation and leucocyte infiltration. Systemic administration of CA significantly reduced CRG-induced paw edema in rats, where CRG-induced iNOS expression and STAT1 phosphorylation were decreased by CA. In summary, CA has significant anti-inflammatory properties both in vitro and in vivo, mediated by significant selective inhibition of JAK2-STAT1 iNOS signaling. CA is an attractive novel candidate for treating inflammatory diseases associated with excessive production of NO. PMID- 27378626 TI - Isolation and characterization of alborixin from Streptomyces scabrisporus: A potent cytotoxic agent against human colon (HCT-116) cancer cells. AB - The ethyl acetate extract from the fermentation broth of an actinomycete strain, identified as Streptomyces scabrisporus isolated from soil of Kashmir Himalayas - India, exhibited significant cytotoxic activity against a panel of human cancer cell lines. The active fraction subjected to column chromatography led to the isolation of pharmacologically potent anticancer compound whose structure was established to be alborixin on the basis of spectral data analysis. The compound exhibited antiproliferative activity against panel of cell lines N2a, MCF-7, MiaPaca-2, PC-3, HCT-116, MDA-MB-231, HL-60 and A-549 cells with IC50 of 9.7, 15.4, 7.2, 8.1, 3.2, 9.7, 7.5 and 11.5 MUM respectively. Alborixin displayed the maximum cytotoxic activity against HCT-116 human colon carcinoma cells and therefore further studies were carried on this cell line. Alborixin decreased the clonogenic potential of HCT-116 cells in a dose dependent manner. It induced apoptotic cell death in HCT116 cells that were confirmed by Flow cytometric analysis of Annexin V/PI staining and microscopic examination of cellular morphology through DAPI-stained cells. Biochemical evidence of apoptosis came from elevating the intracellular ROS level that was accompanied by mitochondrial membrane potential loss, decreasing the expression profile of anti-apoptotic protein Bcl-2, whereas it augments cleavage of caspase-3 and PARP-1, activates caspase-8 and 9 with concomitant increase in expression of proapoptotic protein Bax in a dose dependent manner. These results indicate that alborixin obtained from Streptomyces scabrisporus IIIM55 induces apoptotic cell death in colon cancer cells HCT-116 and can be further evaluated for its potential as an anticancer agent. PMID- 27378627 TI - Expression of globular form acetylcholinesterase is not altered in P2Y1R knock out mouse brain. AB - Adenosine 5'-triphosphate (ATP), a neurotransmitter and a neuromodulator, has been shown to be co-stored and co-released with acetylcholine (ACh) at the pre synaptic vesicles in vertebrate neuromuscular junction (nmj). Several lines of studies demonstrated that binding of ATP to its corresponding P2Y1 receptors (P2Y1R) in muscle and neuron regulated the post-synaptic gene expressions. Indeed, the expression of acetylcholinesterase (AChE) in muscle was markedly decreased in P2Y1R-/- (P2Y1R knock-out) mice. In order to search for possible role of P2Y1R in cholinergic function of the brain, the expression of globular form AChE was determined in the brain of P2Y1R-/- mice. In contrast to that in muscle, the amounts of AChE activity, AChE catalytic subunit, structure subunit PRiMA and the amount of ACh, in the brain were not, significantly, altered, suggesting the role of P2Y1R in neuron could have different function as that in muscle. However, the expressions of a series of neuronal development markers, i.e. neurofilaments, were reduced in P2Y1R-/- mouse brain, indicating P2Y1R may be involved in neuronal development process. PMID- 27378629 TI - Determination of arsenic species in Solanum Lyratum Thunb using capillary electrophoresis with inductively coupled plasma mass spectrometry. AB - A simple and highly efficient interface to couple capillary electrophoresis with inductively coupled plasma mass spectrometry by a microflow polyfluoroalkoxy nebulizer and a quadruple ion deflector was developed in this study. By using this interface, six arsenic species, including arsenite, arsenate, monomethylarsonic acid, dimethylarsinic acid, arsenobetaine, and arsenocholine, were baseline-separated and determined in a single run within 11 min under the optimized separation conditions. The instrumental detection limit was in the range of 0.02-0.06 ng/mL for the six arsenic compounds. Repeatability expressed as the relative standard deviation (n = 5) of both migration time and peak area were better than 2.5 and 4.3% for six arsenic compounds. The proposed method, combined with a closed-vessel microwave-assisted extraction procedure, was successfully applied for the determination of arsenic species in the Solanum Lyratum Thunb samples from Anhui province in China with the relative standard deviations (n = 5) <=4%, method detection limits of 0.2-0.6 ng As/g and a recovery of 98-104%. The experimental results showed that arsenobetaine was the main speciation of arsenic in the Solanum Lyratum Thunb samples from different provinces in China, with a concentration of 0.42-1.30 MUg/g. PMID- 27378630 TI - An investigation of the usability of sound recognition for source separation of packaging wastes in reverse vending machines. AB - In this study, we investigate the usability of sound recognition for source separation of packaging wastes in reverse vending machines (RVMs). For this purpose, an experimental setup equipped with a sound recording mechanism was prepared. Packaging waste sounds generated by three physical impacts such as free falling, pneumatic hitting and hydraulic crushing were separately recorded using two different microphones. To classify the waste types and sizes based on sound features of the wastes, a support vector machine (SVM) and a hidden Markov model (HMM) based sound classification systems were developed. In the basic experimental setup in which only free falling impact type was considered, SVM and HMM systems provided 100% classification accuracy for both microphones. In the expanded experimental setup which includes all three impact types, material type classification accuracies were 96.5% for dynamic microphone and 97.7% for condenser microphone. When both the material type and the size of the wastes were classified, the accuracy was 88.6% for the microphones. The modeling studies indicated that hydraulic crushing impact type recordings were very noisy for an effective sound recognition application. In the detailed analysis of the recognition errors, it was observed that most of the errors occurred in the hitting impact type. According to the experimental results, it can be said that the proposed novel approach for the separation of packaging wastes could provide a high classification performance for RVMs. PMID- 27378628 TI - Low Merlin expression and high Survivin labeling index are indicators for poor prognosis in patients with malignant pleural mesothelioma. AB - INTRODUCTION: Alterations of the tumor suppressor Neurofibromatosis type II (NF2) have been reported in about 40% of Malignant pleural mesothelioma (MPM) patients. NF2 (Merlin) deficiency leads to alterations of the Hippo pathway; resulting in activation of the oncogenic Yes Associated Protein-1 (YAP1). Our aim was to investigate the association between these alterations and clinical outcomes. MATERIAL AND METHODS: Tissue microarrays composed of MPM tumors derived from 2 independent MPM cohorts were employed for this study. Immunohistochemical expression of Merlin, YAP1 and its target genes, Survivin and connective tissue growth factor (CTGF) were assessed in nuclear and cytoplasmic fractions. Cohort 1 was comprised of 145 patients intended to be treated with chemotherapy (CTX) followed by extrapleural pneumonectomy (EPP), thus both pre- and post-CTX tissues were available. Cohort 2 was comprised of 59 patients treated with EPP followed by intraoperative hyperthermic cisplatin and/or adjuvant CTX and/or radiotherapy. Marker expression was quantified by means of labeling index (%) for nuclear Survivin and by H-score for the other markers. The dichotomized marker expression was tested for the association with overall survival (OS) and freedom from recurrence (FFR). RESULTS: Kaplan-Meier survival curves revealed a significant association between low cytoplasmic Merlin expression in pre-induction CTX tissues of cohort 1 with shorter FFR (p = 0.02) and OS (p = 0.03). The same tendency was observed in the chemotherapy naive tissues obtained during EPP of cohort 2. Low nuclear Merlin expression in post-CTX tissues (available from cohort 1 only) was associated with shorter FFR (p = 0.04) and OS (p = 0.05). High nuclear Survivin labeling indices in both pre- and post-CTX tissues of cohort 1 was associated with shorter FFR (p = 0.02). In cohort 2, this was associated with both FFR and OS (p = 0.046 and p = 0.002, respectively). In multivariate analysis, low expression of cytoplasmic Merlin remained an independent prognosticator for shorter FFR of cohort 1 [hazard ratio (HR) = 0.5, 95% confidence interval (CI) = 0.3-0.9, p = 0.001] and OS [HR = 0.5, 95% CI = 0.3-1, p = 0.04]. High Survivin labeling index was an independent prognostic factor for shorter FFR in patients from cohort 1 [HR = 3.4, 95% CI = 1.7-6.8, p = 0.006] and shorter OS in patients from cohort 2 [HR = 2.35, 95% CI = 1.27-4.33, p = 0.006]. CONCLUSIONS: Our findings uncover the significance of Merlin protein expression and Survivin labeling index as prognosticators for poor clinical outcome in two independent MPM cohorts. If confirmed, these markers may be used to identify subgroups of patients benefitting from additional treatment. PMID- 27378631 TI - Signs of low-grade systemic inflammation in female offspring of women with type 1 diabetes: The EPICOM study. PMID- 27378632 TI - Effect of Total Joint Arthroplasty Surgical Day of the Week on Length of Stay and Readmissions: A Clinical Pathway Approach. AB - BACKGROUND: The demand for total joint arthroplasty (TJA) is increasing at the same time that alternative payment models place increased scrutiny on the cost of these procedures. Using a clinical pathway model, this study aimed to examine the effect of day of surgery on length of stay (LOS). METHODS: A retrospective electronic chart review was conducted on 2968 cases over 20 months at a single hospital. Least square means analysis of the effect of surgical day of the week on LOS was conducted using Statistical Analysis Software 9.3, followed by Tukey's multiple comparison test. Logistic regression assessed the effect of surgical day of week on readmission. RESULTS: Within the primary TJA group, there was no significant difference in mean LOS for each day of the week (1.17, 1.32, 1.29, 1.27, and 1.27 for Monday through Friday, respectively). Of all days, mean LOS for revision TJA (1.51, 1.57, 1.57, 2.49, and 2.03) only differed significantly for Thursday (P < .0001), although in adjusted analysis with age and American Society of Anesthesiologist, this difference was no longer significant (P = .3954). Readmission was likewise not significantly affected by surgical day of week (chi sq = 1.426, P = .8396) in the sample. CONCLUSION: As the volume of joint arthroplasties increases and alternative payment models are implemented, programs that promote decreased LOS regardless of operative day of the week are critical. Practices can use clinical pathway models to reduce costs related to LOS while maintaining a high level of patient care. PMID- 27378633 TI - Effect of Preoperative Leg Length Discrepancy on Functional Outcome and Patient Satisfaction After Total Hip Arthroplasty in Cases of Osteonecrosis of the Femoral Head. AB - BACKGROUND: Severe preoperative leg length discrepancy (LLD) can lead to poor preoperative functional status in patients with extensive osteonecrosis of the femoral head (ONFH). This study aimed to assess the effect of preoperative LLD on functional outcomes and patient satisfaction post-total hip arthroplasty (THA) in ONFH patients. METHODS: Twenty-two patients with severe LLD (>=15 mm) and 44 patients with mild LLD (<15 mm) on preoperative radiographs were enrolled as the study group and control group, respectively. All 66 patients were diagnosed with unilateral ONFH. Patients' functional outcomes (Harris Hip Score [HHS], Oxford Hip Score [OHS], patient-perceived LLD, Visual Analogue Scale [VAS] pain score, and Limping Assessment]) and satisfaction (self-administered patient satisfaction scale) were evaluated at 3 and 12 months after THA. RESULTS: At 3 months after THA, the study group had poorer outcomes in terms of the HHS (P = .002) and OHS (P = .002), a higher prevalence of patient-perceived LLD (P = .002), and worse limping (P < .001) than the control group, but the self-administered patient satisfaction scale and VAS pain scores did not differ. However, improvements in the HHS and OHS from preoperative assessment to 3 months were comparable in both groups. At 12 months after THA, there were no significant differences in functional outcomes or self-satisfaction, and the study group showed significantly greater improvements from preoperative assessment to 12 months (P < .05). CONCLUSION: Patients with severe LLD experienced similar improvement at 3 months after THA as those with mild LLD in terms of the HHS and OHS but showed greater improvement at 12 months postoperatively than patients with mild LLD. PMID- 27378634 TI - Is Outpatient Arthroplasty as Safe as Fast-Track Inpatient Arthroplasty? A Propensity Score Matched Analysis. AB - BACKGROUND: In the emerging fiscal climate of value-based decision-making and shared risk and remuneration, outpatient total joint arthroplasty is attractive provided the incidence of costly complications is comparable to contemporary "fast-track" inpatient pathways. METHODS: All patients undergoing total hip arthroplasty or total knee arthroplasty between 2011 and 2013 were selected from the American College of Surgeons-National Surgical Quality Improvement Program database. A propensity score was used to match 1476 fast-track (<=2 day length of stay) inpatients with 492 outpatients (3:1 ratio). Thirty-day complication, reoperation, and readmission rates were compared, both during and after hospitalization. Logistic regression was used to calculate propensity score adjusted odds ratios. RESULTS: After matching, outpatients had higher rates of medical complication (anytime, 10.0% vs 6.7%, P = .018; post discharge, 6.3% vs 1.1%, P < .001). Most complications were bleeding requiring transfusion, which occurred at similar rates after surgery but at higher rates post discharge in outpatients (anytime, 7.5% outpatients vs 5.6% inpatients, P = .113; post discharge, 4.1% outpatients vs 0.1% inpatients, P < .001). There was no difference in readmission rate (2.4% outpatient vs 2.0% inpatient, P = .589). CONCLUSION: Outpatients experience higher rates of post-discharge complications, which may countermand cost savings. Surgeons wishing to implement outpatient total joint arthroplasty clinical pathways must focus on preventing post discharge medical complications to include blood management strategies. PMID- 27378635 TI - Epidemiology of Dislocation Following Direct Anterior Total Hip Arthroplasty: A Minimum 5-Year Follow-Up Study. AB - BACKGROUND: The cumulative mid- to long-term risk of dislocation following total hip arthroplasty is considerably greater than has been reported in short-term studies. We retrospectively investigated the epidemiology of first-time dislocation following total hip arthroplasty using 28-mm heads through the direct anterior approach in patients with hip dysplasia who were followed up for more than 5 years. METHODS: The operative records of 871 hips in 790 consecutive patients were reviewed to determine the incidence of postoperative first-time dislocation. RESULTS: The mean follow-up duration was 7.8 (range, 5.6-11.7) years. The direct anterior approach was used for all hips. Postoperative dislocation was observed in 8 hips (0.92%) in 8 patients. First-time dislocation occurred during the first 3 weeks in 6 hips (75%). The cumulative risk of postoperative dislocation was 0.69% at 1 month, 0.80% at 1 year, and 0.93% at 5 years. One patient underwent revision surgery for recurrent dislocation within the first month due to malalignment of the cup. CONCLUSION: Our findings demonstrated that the direct anterior approach limits the time of dislocation to the very early postoperative period; that is, the risk of a first-time dislocation after the first month is considerably low. Preserving muscular structures may contribute to continuous dynamic stability of the hip, which could explain the slight increase in the cumulative risk of first-time dislocation. PMID- 27378636 TI - Patient Perception of Value in Bundled Payments for Total Joint Arthroplasty. AB - BACKGROUND: A central concern for providers in a bundled payment model is determining how the bundle is distributed. Prior studies have shown that current reimbursement rates are often not aligned with patients' values. While willingness-to-pay (WTP) surveys are perhaps useful in a fee-for-service arrangement to determine overall reimbursement, the percentage of payment distribution might be as or more important in a bundled payment model. METHODS: All patients undergoing primary total joint arthroplasty by a single surgeon were offered participation in a preoperative WTP survey. At a minimum 3 months postoperatively, patients were mailed instructions for an online follow-up survey asking how they would allocate a hypothetical bonus payment. RESULTS: From January through December 2014, 45 patients agreed to participate in the preoperative WTP survey. Twenty patients who were minimum 3 months postoperative also completed the follow-up survey. Patients valued total knee and hip arthroplasty at $28,438 (95% confidence interval [CI]: $20,551-36,324) and $39,479 (95% CI: $27,848-$51,112), respectively. At 3 months postoperatively, patients distributed a hypothetical bonus payment 55.5% to the surgeon (95% CI: 47.8%-63.1%), 38% to the hospital (95% CI: 30.3%-45.7%), and 6.5% (95% CI: -1.2% to 14.2%) to the implant manufacturer (P < .001). CONCLUSION: The data suggest that total joint arthroplasty patients have vastly different perceptions of payment distributions than what actually exists. In contrast to the findings of this study, the true distribution of payments for an episode of care averages 65% to the hospital, 27% to the implant manufacturer, and 8% to the surgeon. While many drivers of payment distribution exist, this study suggests that patients would allocate a larger proportion of a bundled payment to surgeons than is currently disbursed. This finding may also provide a plausible explanation for patients' consistent overestimation of surgeon reimbursements. PMID- 27378637 TI - Outcome of Revision Total Hip Arthroplasty in Management of Failed Metal-on-Metal Hip Arthroplasty. AB - BACKGROUND: This is a retrospective review of the functional outcomes and complications of revision total hip arthroplasty (THA) of failed metal-on-metal (MoM) hip arthroplasty. METHODS: A total of 20 revision THAs were performed in 19 patients. Of them, 2 cases were failed hip resurfacing, and 18 cases were failed (MoM) THA. The mean age at revision (THA) was 59.35 years (standard deviation [SD] 9.83). RESULTS: The mean follow-up was 45 months (SD 13.98). The indications of revision were aseptic loosening of acetabular component without adverse local tissue reaction (ALTR; 10 hips), aseptic loosening of the acetabular and femoral components without ALTR (1 hip), painful hip associated with ALTR (6 hips), iliopsoas impingement associated with a large-diameter femoral head or malpositioned acetabular component (3 hips). The acetabular components were revised in 18 hips using Trabecular Metal Modular cups. The femoral components were revised in 3 hips. A constrained acetabular liner was used in 5 hips. The Harris hip score significantly improved from 48.4 (SD 12.98) to 83.25 (SD 10.08). There were 2 complications (1 foot drop and 1 superficial infection) and 1 failure (recurrent dislocation) that required revision to a constrained liner. CONCLUSION: Early results of revision THA of failed MoM hip arthroplasty showed improvement in pain and functional outcome. No case of failed bone ingrowth was noted with the use of Trabecular Metal Modular cups. Extensive soft tissue and abductor muscles dysfunctions were common. A constrained acetabular component with repair of the hip abductors might be beneficial. PMID- 27378638 TI - Preoperative Predictors of Pain Catastrophizing, Anxiety, and Depression in Patients Undergoing Total Joint Arthroplasty. AB - BACKGROUND: The relationship between pain catastrophizing and emotional disorders including anxiety and depression in osteoarthritic patients undergoing total joint arthroplasty (TJA) is an emerging area of study. The purpose of this study was to examine the association of these factors with preoperative patient characteristics. METHODS: A prospective cohort study of preoperative TJA patients using the Pain Catastrophizing Scale (PCS) and Hospital Anxiety and Depression Scale (HADS-A/HADS-D) was conducted. Preoperative measures included visual analog pain scale (VAS), Harris Hip and Knee Society scores, Oxford Score, and Kellgren Lawrence grade. Logistic and quantile regression were used to assess the relationship between preoperative characteristics and PCS or HADS, adjusting for covariate effects. RESULTS: We recruited 463 TJA patients. VAS pain (odds ratio [OR] 1.23; 95% confidence interval [CI] 1.04-1.45) and Oxford (OR 1.13; 95% CI 1.07-1.20) were significant predictors for PCS and its subdomains excluding rumination. Oxford was the only significant predictor for abnormal HADS-A (OR 1.10; 95% CI 1.04-1.17). VAS pain (OR 1.27; 95% CI 1.02-1.52) and Oxford (OR 1.09; 95% CI 1.01-1.17) were significant predictors for abnormal HADS-D. The quantile regression showed similar patterns of association, with female gender, younger age, and higher ASA also associated with HADS-A. CONCLUSION: The most important predictor of catastrophizing, anxiety and/or depression in TJA patients is preoperative pain and poor subjective function. At-risk patients include those with increased pain and generally good clinical function, as well as younger women with significant comorbidities. Such patients should be identified and targeted psychological therapy implemented preoperatively to optimize coping strategies and adaptive behavior to mitigate potential for inferior TJA outcomes including pain and patient dissatisfaction. PMID- 27378639 TI - Alumina Delta-on-Highly Crosslinked-Remelted Polyethylene Bearing in Cementless Total Hip Arthroplasty in Patients Younger than 50 Years. AB - BACKGROUND: The purpose of this retrospective study was to determine the clinical and radiographic results, prevalence of polyethylene wear and osteolysis, and fracture of alumina delta ceramic femoral head or highly crosslinked, remelted polyethylene (HXLPE) liner associated with the use of alumina delta ceramic femoral head-on-HXLPE bearing in cementless total hip arthroplasty in patients younger than 50 years. METHODS: We reviewed the cases of 119 patients (130 hips) who underwent a cementless total hip arthroplasty using alumina delta ceramic-on HXLPE bearing when they were 50 years or younger at the time of surgery. The most common diagnoses were osteonecrosis (51%) and osteoarthritis secondary to developmental dysplastic hip (39%). Osteolysis and polyethylene wear rates were evaluated with use of radiography and computed tomography. In addition, prevalence of fracture of alumina delta ceramic head and polyethylene line was documented. The mean follow-up was 8.3 years (range, 7-9 years). RESULTS: The mean Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index score, University of California, Los Angeles activity score were 94 points, 14 points, and 8.1 points, respectively, at the final follow-up. No patient had thigh pain. All acetabular components and all but one femoral components were well fixed. The mean annual penetration rate of femoral head was 0.022 +/- 0.003 mm/year. No hip had osteolysis or ceramic head or HXLPE liner fracture. CONCLUSION: Our average 8.3-year results with the use of alumina delta ceramic-on HXLPE bearing in the patients younger than 50 years suggest that cementless acetabular and femoral components provide a high survival rate without evidence of osteolysis or ceramic head or AXLPE liner fracture. PMID- 27378640 TI - Proximal Femur Bone Density Decreases up to 5 Years After Total Hip Arthroplasty in Young, Active Patients. AB - BACKGROUND: The number of young, active patients undergoing hip arthroplasty continues to increase. The purpose of this study was to evaluate femoral bone density over a 5-year period after hip arthroplasty in young, active patients. METHODS: A total of 96 patients (103 hips) with a presymptomatic University of California at Los Angeles (UCLA) score >=6 who had a total hip arthroplasty (THA; 45 hips) or surface replacement arthroplasty (SRA; 58 hips) were prospectively enrolled. UCLA and Harris Hip Scores were collected preoperatively and postoperatively, and dual energy X-ray absorptiometry scans were performed at 6 weeks, 6 months, 1 year, 2 years, and 5 years postoperatively. Bone density was analyzed for 7 traditional Gruen zones in both groups and 6 femoral neck zones in the SRA group. Bone density ratios were calculated for change in bone density compared with baseline. RESULTS: No differences were present in the preoperative or postoperative UCLA or Harris Hip Scores between the SRA and THA cohorts (P = .07-.7). In the THA group, bone density never returned to baseline during the 5 year period in Gruen zones 1 (91.2% of baseline), 2 (94.8%), 6 (97.3%), and 7 (89.2%). There were no decreases in bone mineral density ratio for the femoral Gruen zones in the SRA group at any interval. Femoral neck bone density after SRA increased on the lateral, tension side up to 5 years postoperatively (P < .0001). CONCLUSION: Young, active patients undergoing THA with cementless femoral fixation demonstrate reductions in bone density in the proximal femur in Gruen zones 1, 2, and 7 over time. PMID- 27378641 TI - Letter to the Editor on "What Do Scottish Patients Expect of Their Total Knee Arthroplasty?". PMID- 27378642 TI - Improved Resistance to Neck-Liner Impingement in Second-Generation Highly Crosslinked Polyethylene-The Role of Vitamin E and Crosslinks. AB - BACKGROUND: Radiation crosslinking of ultrahigh molecular weight polyethylene (UHMWPE) results in the reduced tensile strength and fracture toughness as an expense of dramatic increase in the wear resistance. Clinical rim fracture has been reported due to neck-liner impingement on a first-generation highly crosslinked UHMWPE acetabular component. The objective of this study was to investigate whether a second-generation, vitamin E-blended highly crosslinked UHMWPE possesses the improved impingement resistance. METHODS: Cyclic impingement testing was performed in a variety of UHMWPE acetabular components (vitamin E free or blended, noncrosslinked or highly crosslinked, and GUR1050 or GUR1020) with the same design specification. The kinematics used to reproduce the neck liner impingement was a uniaxial fatigue compression in concert with an axial rotational torque. After the test, the geometry and morphological changes were characterized by coordinate measuring machine, scanning electron microscopy, and confocal Raman microspectroscopy. RESULTS: A total of 300-kGy irradiated and annealed GUR1050 liner resulted in a significant geometry change and microcracks on the rim surface after the test. However, regardless of the similar level of crosslinking, much less damage was noted in the 300-kGy irradiated GUR1050 liner blended with vitamin E at a concentration of 3000 ppm. On the other hand, vitamin E-blended noncrosslinked GUR1050 exhibited an extensive microscopic fibrillation and folding on the impinged surface. CONCLUSION: These results suggest that vitamin E-blending into UHMWPE has compensated the negative effect of toughness decrease induced by radiation crosslinking. We concluded that the coexistence of vitamin E and crosslinks can restrain impingement damage more effectively than either of them. PMID- 27378643 TI - Disparities in Discharge Destination After Lower Extremity Joint Arthroplasty: Analysis of 7924 Patients in an Urban Setting. AB - BACKGROUND: Discharge destination is an important factor to consider to maximize care coordination and manage patient expectations after total joint arthroplasty (TJA). It also has significant impact on the cost-effectiveness of these procedures given the significant cost of post-acute inpatient care. Therefore, understanding factors that impact discharge destination after TJA is critical. METHODS: An evaluation of socioeconomic, geographic, and racial/ethnic factors associated with discharge destination to either home or institution (ie, rehabilitation, skilled nursing facility, and so forth) following joint arthroplasty of the lower extremity was conducted. We analyzed data on patients admitted between 2011 and 2014 for primary or revision hip or knee arthroplasty at a single institution. Bivariate and multivariate statistical techniques were applied to determine associations. RESULTS: Included in the analysis were 7924 cases of lower extremity joint procedures, of which 4836 (61%), 785 (10%), and 2770 (35%) were of female gender, low socioeconomic status, and nonwhite race/ethnicity, respectively. A total of 5088 (64%) and 2836 (36%) cases were discharged to home and institution, respectively. Significant predictors of discharge to an institution in the multivariate analysis include SES (low and middle SES [odds ratio {OR}: 1.27, 95% confidence interval {CI}: 1.02-1.57, P = .029; and OR: 1.26, 95% CI: 1.10-1.44, P = .001]), age (OR: 1.05, 95% CI: 1.049 1.060, P < .001), female gender (OR: 1.69, 95% CI: 1.52-1.89, P < .001) and TKA procedure (OR: 1.48, 95% CI: 1.33-1.64, P < .001). Patients of nonblack race/ethnicity were more likely to be discharged home (white OR: 0.84, 95% CI: 0.72-0.98, P = .027; other OR: 0.80, 95% CI: 0.67-0.95, P = .009). CONCLUSION: Socioeconomic status and race/ethnicity are important factors related to discharge destination following TJA. Thoroughly understanding and addressing these factors may help increase the rates of discharge to home as opposed to institution. PMID- 27378644 TI - Incidence, Risk Factors, and Sources of Sepsis Following Total Joint Arthroplasty. AB - BACKGROUND: Sepsis is a rare but serious complication following total joint arthroplasty (TJA). Common sources include urinary tract infection (UTI), surgical site infection (SSI), and pneumonia. The purpose of this study is to characterize the incidence, risk factors, and sources of sepsis following TJA. METHODS: Patients undergoing primary total hip arthroplasty or total knee arthroplasty during 2005-2013 were identified in the American College of Surgeons National Surgical Quality Improvement Program database. Independent associations were tested for using multivariate regression adjusting for baseline characteristics. RESULTS: A total of 117,935 patients were identified (45,612 undergoing total hip arthroplasty and 72,323 undergoing total knee arthroplasty). Of these, 402 (0.34%) developed sepsis following surgery. Patients who developed sepsis had an elevated mortality rate (3.7% vs 0.1%, P < .001). Among the 402 patients who developed sepsis, 124 (31%) had concomitant UTI, 110 (27%) SSI, and 60 (15%) pneumonia. Twenty-one patients (5%) had multiple infectious sources and 129 patients (32%) had no identifiable source. Independent risk factors for sepsis included greater age, male sex, functional dependence, insulin-dependent diabetes, hypertension, chronic obstructive pulmonary disease, current smoker, and greater operative time. CONCLUSION: These findings suggest that the rate of sepsis following TJA is about 1 in 300, and that sepsis is associated with a high risk of mortality. The most common sources of sepsis are UTI, SSI, and pneumonia, potentially accounting for at least two-thirds of cases. The information provided here can be used to guide the diagnostic workup of sepsis in patients following TJA. PMID- 27378645 TI - American Association of Hip and Knee Surgeons-Endorsed Comorbidity Coding for Total Joint Arthroplasty: How Often Did We Hit the Mark With International Classification of Diseases, Ninth Revision? AB - BACKGROUND: Initiatives led by the American Academy of Orthopaedic Surgeons and the American Association of Hip and Knee Surgeons (AAHKS) have indicated a number of clinical risk factors associated with total joint arthroplasty that might reflect the complexity of contemporary hip and knee care. This study sought to examine the prevalence of specific International Classification of Diseases, Ninth Revision (ICD-9), coding with respect to an AAHKS-endorsed list of comorbidity codes. METHODS: An administrative data set from an academic arthroplasty referral center was analyzed in an attempt to measure the prevalence of clinical risk factors (ICD-9) endorsed by AAHKS. Total, partial, and revision joint arthroplasty procedures from January 1, 2012, to April 27, 2015, were included. Demographic data, along with diagnosis and procedural coding data, were collected and analyzed. RESULTS: Results analysis found a number of poorly coded variables. The following variables were omitted in the data: narcotic use, worker's compensation status, previous intra-articular infection, previous open reduction and internal fixation knee, and depression/psychiatric disease. Likewise, there was a discrepancy between the rate of ICD coding for obesity and body mass index measurements and categorization recorded in the clinic. CONCLUSION: From this single-center study, there remain opportunities for coding to adequately reflect the comorbidities and complexities of patients undergoing arthroplasty. PMID- 27378646 TI - The Fate of Allogeneic Femoral Head Bone Grafts Using Varus-Valgus Constrained Total Knee Arthroplasty in Neuropathic Joints. AB - BACKGROUND: This study was conducted to assess the clinical and radiological results of total knee arthroplasty (TKA) with an allogeneic bone graft using varus-valgus constrained (VVC) prostheses in knees with severe bone defects and unstable neuropathy. METHODS: This study included 20 knees of 16 patients who underwent TKA between August 2001 and January 2006 due to unstable knees with severe bone destruction resulting from neuropathic arthritis. At the time of surgery, the mean age of the patients was 56 years. The mean length of the follow up period was 10.7 years. A VVC condylar prosthesis was used with an allogeneic femoral head graft to reconstruct large bony defects. Clinical results were evaluated using the Hospital for Special Surgery, Knee Society function, and Western Ontario and McMaster Universities Osteoarthritis scores. Three dimensional computed tomography was used to evaluate the radiological parameters, which included the tibiofemoral angle, loosening or osteolysis of components, and incorporation of the bone graft. RESULTS: The preoperative mean Hospital for Special Surgery, Knee Society function, and Western Ontario and McMaster Universities Osteoarthritis scores were 40.5, 43.2, and 78.3, respectively, and these scores improved to 86.0, 64.6, and 33.8, respectively at the final follow up. The mean postoperative alignment was 6.1 degrees of valgus angulation. One knee had instability, another knee had partial bony absorption, which was confirmed using 3-dimensional computed tomography, and the other 18 cases (90%) had satisfactory results. No cases experienced radiolucency, fracture, or infection. CONCLUSIONS: TKA with an allogeneic bone graft using a VVC prosthesis provides a viable option for the treatment of severe bone defects with soft tissue insufficiency in neuropathic knee arthropathy. PMID- 27378647 TI - Recurrent Periprosthetic Joint Infection After Irrigation and Debridement With Component Retention Is Most Often Due to Identical Organisms. AB - BACKGROUND: Irrigation and debridement with prosthetic retention (I&D) is an oft utilized treatment option for PJI, despite its known limited success. While it is known that nearly half of all patients treated with I&D have recurrent infection, the organism persistence between infection events remains unreported. In addition, identifying those cases in which I&D routinely failed to eradicate the infection (not simply prevent recurrent infection) may allow improved patient selection for this less morbid procedure-a difficult task to date. METHODS: Using an institutional database, 146 patients (153 joints) undergoing I&D between April 2000 and July 2013 were identified. There were 60 hips (40%). The overall success rate of I&D in this group was 52% (80/153). The failure group was limited to those patients with growth on culture at both initial failure and recurrent failure (46 cases). Analyses were performed to identify potential predictors of failed I&D and organism persistence in those cases. RESULTS: In the study group, 83.7% (36/43) of cases failed with the same organism. Knees with failed I&D had an organism persistence of 92.3% (24/26) compared with 70.5% (12/17; P = .09) for the hip. Patients initially infected with Staphylococcus aureus (specifically methicillin-resistant [13/13]) had a higher risk of persistent PJI (96%; 24/25) compared to other organisms (66.7%; 12/18; P = .01). CONCLUSION: I&D had a success rate of approximately 50% and typically failed due to organism persistence rather than a new infection. Given that persistent infection was most common in knees and S aureus, I&D should have a limited role in treating PJI, especially in these cases. PMID- 27378648 TI - Targeted fluorescence imaging enhanced by 2D materials: a comparison between 2D MoS2 and graphene oxide. AB - Here we demonstrate that 2D MoS2 can enhance the receptor-targeting and imaging ability of a fluorophore-labelled ligand. The 2D MoS2 has an enhanced working concentration range when compared with graphene oxide, resulting in the improved imaging of both cell and tissue samples. PMID- 27378649 TI - Green tea extract as an anti-browning agent for cloudy apple juice. AB - BACKGROUND: Enzymatic browning of fruits and vegetables and their products is an important factor worsening their quality. The influence of five green tea extracts at the concentrations of 1 g L-1 , 2 g L-1 and 3 g L-1 on polyphenol oxidase (PPO) activity in fresh cloudy apple juice was investigated. Moreover, PPO inhibition by tea extract and colour stability of juice during short-time refrigerated storage was studied. The changes of juice colour during storage was expressed as the total colour differences (DeltaE*), browning index (BI), yellowness index (YI), and the absorbance at 420 nm (A420 ). RESULTS: All extracts inhibited PPO activity in fresh apple juice in concentration-dependent manner. PPO activity in pure apple juice decreased by 7% after 48 h, whereas PPO activity in samples with 1 g L-1 , 2 g L-1 and 3 g L-1 tea extract decreased by 53%, 74%, and 96%, respectively. Browning of apple juice during storage decreased with increased concentration of green tea extract. After 48 h, extract at 1 g L-1 , 2 g L-1 and 3 g L-1 inhibited browning of juice expressed as BI by 48%, 60%, and 86%, respectively, comparing to pure apple juice. CONCLUSION: Green tea extract may be an effective anti-browning agent for short-time stored cloudy apple juices. (c) 2016 Society of Chemical Industry. PMID- 27378650 TI - What is your diagnosis? Tracheobronchial lavage from a dog. PMID- 27378651 TI - Age-dependent effects on social interaction of NMDA GluN2A receptor subtype selective antagonism. AB - NMDA receptor-mediated neurotransmission is implicated in the regulation of normal sociability in mice. The heterotetrameric NMDA receptor is composed of two obligatory GluN1 and either two "modulatory" GluN2A or GluN2B receptor subunits. GluN2A and GluN2B-containing receptors differ in terms of their developmental expression, distribution between synaptic and extrasynaptic locations, and channel kinetic properties, among other differences. Because age-dependent differences in disruptive effects of GluN2A and GluN2B subtype-selective antagonists on sociability and locomotor activity have been reported in rats, the current investigation explored age-dependent effects of PEAQX, a GluN2A subtype selective antagonist, on sociability, stereotypic behaviors emerging during social interaction, and spatial working memory in 4- and 8-week old male Swiss Webster mice. The data implicate an age-dependent contribution of GluN2A containing NMDA receptors to the regulation of normal social interaction in mice. Specifically, at a dose of PEAQX devoid of any effect on locomotor activity and mouse rotarod performance, the social interaction of 8-week old mice was disrupted without any effect on the social salience of a stimulus mouse. Moreover, PEAQX attenuated stereotypic behavior emerging during social interaction in 4- and 8-week old mice. However, PEAQX had no effect on spontaneous alternations, a measure of spatial working memory, suggesting that neural circuits mediating sociability and spatial working memory may be discrete and dissociable from each other. Also, the data suggest that the regulation of stereotypic behaviors and sociability may occur independently of each other. Because expression of GluN2A-containing NMDA receptors occurs at a later developmental stage, they may be more involved in mediating the pathogenesis of ASDs in patients with histories of "regression" after a period of normal development than GluN2B receptors. PMID- 27378652 TI - Oviposition site selection and survival of susceptible and resistant larvae of Helicoverpa armigera (Lepidoptera: Noctuidae) on Bt and non-Bt cotton. AB - In Australia Bt cotton has been planted since 1996, and has greatly improved the control of its key target Helicoverpa armigera (Hubner). There is no strong evidence that genetically modified cotton has been selected for significant physiological resistance to Bt toxin in field populations. There are many possible explanations for the lack of apparent selection that range from high compliance with the resistance management strategy for this technology to a lack of behavioral preference in key traits such as oviposition that could favor survival. To date most experiments that test oviposition of H. armigera on Bt cotton vs. conventional cotton have been done with susceptible moths. We determine the oviposition preference of a field isolated Bt resistant line of H. armigera and a susceptible counterpart when given a choice of non-Bt cotton and Bt-cotton with the same genetic background, and test whether there is any relationship between oviposition site selection (different plant structures) and the survival of the first instar larvae. Within cotton plants, our experiments consistently showed that both resistant and susceptible moths did not choose plants or plant parts that were less toxic in terms of Bt toxin on which to lay eggs. There was one exception in that susceptible moths were more likely to lay eggs on squares of Bt cotton plants than squares of non-Bt cotton. As expected, the mortality of susceptible H. armigera neonates was significantly higher on structures of Bt cotton plants than on those structures of conventional cotton, and survival was greater on flowers than on other structures of Bt cotton. This confirms opportunities for selection for resistance, and demonstrates no advantage in this respect to carrying resistance genes that might overcome the Bt toxins. PMID- 27378653 TI - Na3 SbS4 : A Solution Processable Sodium Superionic Conductor for All-Solid-State Sodium-Ion Batteries. AB - All-solid-state sodium-ion batteries that operate at room temperature are attractive candidates for use in large-scale energy storage systems. However, materials innovation in solid electrolytes is imperative to fulfill multiple requirements, including high conductivity, functional synthesis protocols for achieving intimate ionic contact with active materials, and air stability. A new, highly conductive (1.1 mS cm(-1) at 25 degrees C, Ea =0.20 eV) and dry air stable sodium superionic conductor, tetragonal Na3 SbS4 , is described. Importantly, Na3 SbS4 can be prepared by scalable solution processes using methanol or water, and it exhibits high conductivities of 0.1-0.3 mS cm(-1) . The solution-processed, highly conductive solidified Na3 SbS4 electrolyte coated on an active material (NaCrO2 ) demonstrates dramatically improved electrochemical performance in all-solid-state batteries. PMID- 27378654 TI - Boosting compound-protein interaction prediction by deep learning. AB - The identification of interactions between compounds and proteins plays an important role in network pharmacology and drug discovery. However, experimentally identifying compound-protein interactions (CPIs) is generally expensive and time-consuming, computational approaches are thus introduced. Among these, machine-learning based methods have achieved a considerable success. However, due to the nonlinear and imbalanced nature of biological data, many machine learning approaches have their own limitations. Recently, deep learning techniques show advantages over many state-of-the-art machine learning methods in some applications. In this study, we aim at improving the performance of CPI prediction based on deep learning, and propose a method called DL-CPI (the abbreviation of Deep Learning for Compound-Protein Interactions prediction), which employs deep neural network (DNN) to effectively learn the representations of compound-protein pairs. Extensive experiments show that DL-CPI can learn useful features of compound-protein pairs by a layerwise abstraction, and thus achieves better prediction performance than existing methods on both balanced and imbalanced datasets. PMID- 27378655 TI - Multilocular Facial Necrosis in a Young Boy: A Quiz. PMID- 27378656 TI - Restoring movement representation and alleviating phantom limb pain through short term neurorehabilitation with a virtual reality system. AB - BACKGROUND AND OBJECTIVE: We developed a quantitative method to measure movement representations of a phantom upper limb using a bimanual circle-line coordination task (BCT). We investigated whether short-term neurorehabilitation with a virtual reality (VR) system would restore voluntary movement representations and alleviate phantom limb pain (PLP). METHODS: Eight PLP patients were enrolled. In the BCT, they repeatedly drew vertical lines using the intact hand and intended to draw circles using the phantom limb. Drawing circles mentally using the phantom limb led to the emergence of an oval transfiguration of the vertical lines ('bimanual-coupling' effect). We quantitatively measured the degree of this bimanual-coupling effect as movement representations of the phantom limb before and immediately after short-term VR neurorehabilitation. This was achieved using an 11-point numerical rating scale (NRS) for PLP intensity and the Short-Form McGill Pain Questionnaire (SF-MPQ). During VR neurorehabilitation, patients wore a head-mounted display that showed a mirror-reversed computer graphic image of an intact arm (the virtual phantom limb). By intending to move both limbs simultaneously and similarly, the patients perceived voluntary execution of movement in their phantom limb. RESULTS: Short-term VR neurorehabilitation promptly restored voluntary movement representations in the BCT and alleviated PLP (NRS: p = 0.015; 39.1 +/- 28.4% relief, SF-MPQ: p = 0.015; 61.5 +/- 48.5% relief). Restoration of phantom limb movement representations and reduced PLP intensity were linearly correlated (p < 0.05). CONCLUSIONS: VR rehabilitation may encourage patient's motivation and multimodal sensorimotor re-integration of a phantom limb and subsequently have a potent analgesic effect. SIGNIFICANCE: There was no objective evidence that restoring movement representation by neurorehabilitation with virtual reality alleviated phantom limb pain. This study revealed quantitatively that restoring movement representation with virtual reality rehabilitation using a bimanual coordination task correlated with alleviation of phantom limb pain. PMID- 27378658 TI - Risk factors' management to impact on acute coronary syndromes. PMID- 27378657 TI - Precise and accurate assay of pregnenolone and five other neurosteroids in monkey brain tissue by LC-MS/MS. AB - A series of steroids present in the brain have been named "neurosteroids" following the possibility of their role in the central nervous system impairments such as anxiety disorders, depression, premenstrual dysphoric disorder (PMDD), addiction, or even neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Study of their potential role requires a sensitive and accurate assay of their concentration in the monkey brain, the closest model to the human. We have thus developed a robust, precise and accurate liquid chromatography-tandem mass spectrometry method for the assay of pregnenolone, pregnanolone, epipregnanolone, allopregnanolone, epiallopregnanolone, and androsterone in the cynomolgus monkey brain. The extraction method includes a thorough sample cleanup using protein precipitation and phospholipid removal, followed by hexane liquid-liquid extraction and a Girard T ketone-specific derivatization. This method opens the possibility of investigating the potential implication of these six steroids in the most suitable animal model for neurosteroid-related research. PMID- 27378659 TI - Angiotensin receptor-neprilysin inhibitor (ARNi): Clinical studies on a new class of drugs. AB - Sacubritil*valsartan (Entresto, Novartis, still commonly referred to as LCZ696) is a combination drug described as a new class of dual-acting angiotensin receptor-neprilysin inhibitor (ARNi). This combination drug has been successfully studied in patients with heart failure with both preserved (HFpEF) and reduced ejection fraction (HFrEF). In this review, the evidences in patients with HFpEF and HFrEF are summarized, including the results of more recent studies. PMID- 27378660 TI - Contemporary roles of registries in clinical cardiology: Insights from Western and Eastern European countries. PMID- 27378662 TI - The diplomats. PMID- 27378661 TI - Coronary heart disease differences in Eastern versus Western Europe: A demanding situation. PMID- 27378665 TI - Thermodynamics of N-H bond formation in bis(phosphine) molybdenum(ii) diazenides and the influence of the trans ligand. AB - A series of bis(phosphine) molybdenum(ii) diazenides [(dppe)2Mo(NNCy)(I)], [(dppe)2(CH3CN)Mo(NNCy)][BArF24] and [(dppe)2)(3,5-(CF3)2C6H3CN)Mo(NNCy)][BArF24] (dppe = 1,2-bis(diphenylphosphino)ethane; Cy = cyclohexyl; ArF24 = (3,5 (CF3)2C6H3)4) were synthesized and structurally characterized. Treatment of the diazenido complexes with a stoichiometric amount of [H(OEt2)2][BArF24] afforded the corresponding molybdenum(iv) hydrazido species [(dppe)2Mo(NNHCy)(I)][BArF24], [(dppe)2(CH3CN)Mo(NNHCy)][BArF24]2 and [(dppe)2(3,5 (CF3)2C6H3CN)Mo(NNHCy)][BArF24]2, enabling the study of N-H bond dissociation free energies (BDFEs) in the classical Chatt-type bis(phosphine) diazenide platform as a function of ligand (L) trans to the nitrogenous fragment. Deprotonation and electrochemical experiments established that the trans nitrile 3,5-(CF3)2C6H3CN afforded the least reducing molybdenum(iv) hydrazido complex in the series ( = -1.32 V vs. Fc/Fc+) with the most acidic N-H bond (pKa < 2.6, THF), whereas the ligands CH3CN ( = -1.60 V, pKa < 5.5) and I- ( = -2.03 V, pKa = 9.3) gave more reducing complexes with less acidic N-H bonds. Computational (DFT) studies confirm weak N-H bond strengths of 32.8 (L = I-), 35.4 (L = CH3CN) and 36.2 kcal mol-1 (L = 3,5-(CF3)2C6H3CN) in the hydrazido series. PMID- 27378666 TI - Vascular calcification: How an evolutionary approach may help to shed light on its significance. PMID- 27378667 TI - Editorial Commentary: Sudden cardiac death: We shall never surrender. PMID- 27378668 TI - Enhancement of the electrical properties of silver nanowire transparent conductive electrodes by atomic layer deposition coating with zinc oxide. AB - Transparent conductive electrodes for applications in optoelectronic devices such as solar cells and light-emitting diodes are important components and require low sheet resistance and high transmittance. Herein, we report an enhancement of the electrical properties of silver (Ag) nanowire networks by coating with zinc oxide using the atomic layer deposition technique. A strong decrease in the sheet resistance of Ag nanowires, namely from 20-40 Omega/? to 7-15 Omega/?, was observed after coating with ZnO. Ag nanowire electrodes coated with 200-cycle ZnO by atomic layer deposition show the best quality, with a sheet resistance of 11 Omega/? and transmittance of 75%. PMID- 27378669 TI - Re: Brown, Sharma, Ardern, et al., Secular changes in the association between caloric intake, macronutrient intake and physical activity with obesity. PMID- 27378670 TI - Reprint of: Obesity and social factors. PMID- 27378671 TI - Reprint of: Response to the Letter to the Editor: "Re: Ruth E. Brown, Arya M. Sharma, Chris I. Ardern, Pedi Mirdamadi, Paul Mirdamadi and Jennifer L. Kuk, 'Secular differences in the association between caloric intake, macronutrient intake, and physical activity with obesity' [Obes. Res. Clin. Pract. (2015)]". PMID- 27378672 TI - Reprint of: Ruth E. Brown, Arya M. Sharma, Chris I. Ardern, Pedi Mirdamadi, Paul Mirdamadi and Jennifer L. Kuk. "Secular differences in the association between caloric intake, macronutrient intake, and physical activity with obesity." [Obesity Research & Clinical Practice (2015)]. PMID- 27378673 TI - High-affinity von Willebrand factor binding does not affect the anatomical or hepatocellular distribution of factor VIII in rats. AB - Essentials Von Willebrand factor (VWF) stabilizes factor VIII (FVIII) and prevents its premature clearance. Rat anatomical and hepatocellular distribution studies assessed the VWF effect on FVIII clearance. Hepatocytes and liver sinusoidal endothelial cells play a key role in FVIII clearance. Anatomical and hepatocellular distribution of FVIII is independent of high-affinity VWF binding. ABSTRACT: Background Von Willebrand factor (VWF) stabilizes factor VIII in the circulation and prevents its premature clearance. Objective To study the effects of VWF on FVIII clearance in rats with endogenous VWF. Methods Anatomical and hepatocellular distribution studies were performed in rats following intravenous administration of glycoiodinated recombinant FVIII (rFVIII) and a FVIII variant, FVIII-Y1680F, lacking high-affinity VWF binding. Radioactivity was quantified in organs, and in distinct liver cell populations. The role of VWF binding was also studied by immunohistochemical staining of rat livers perfused ex vivo with rFVIII alone or with a FVIII-binding VWF fragment. Results The liver was the predominant organ of rFVIII distribution, and a radioactivity peak was also observed in the intestines, suggesting FVIII secretion to the bile by hepatocytes. In the liver, ~60% of recovered radioactivity was associated with hepatocytes, 32% with liver sinusoidal endothelial cells (LSECs), and 9% with Kupffer cells (KCs). When calculated per cell, 1.5-fold to 3-fold more radioactivity was associated with LSECs than with hepatocytes. The importance of hepatocytes and LSECs was confirmed by immunohistochemical staining; strong staining was seen in LSECs, and less intense, punctate staining in hepatocytes. Minor staining in KCs was observed. Comparable anatomical and hepatocellular distributions were observed with rFVIII and FVIII-Y1680F, and the presence of the VWF fragment, D'D3A1, did not change the FVIII staining pattern in intact livers. Conclusions The present data support FVIII clearance via the liver, with hepatocytes and LSECs playing a key role. High-affinity VWF binding did not alter the anatomical or hepatocellular distribution of FVIII. PMID- 27378674 TI - 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau. AB - In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 11.4 years: For all patients on an intent to-treat basis, the median overall and progression-free survival was 12.7 and 8.5 years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12 years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL. PMID- 27378675 TI - Retrospective analysis of therapeutic effect and prognostic factors on early glottic carcinoma. AB - OBJECTIVE: To investigate the therapeutic effect of surgery, radiotherapy and photodynamic therapy on early glottic carcinoma and prognostic factors. METHODS: Retrospective analysis of 202 cases with early glottic carcinoma (Tis-T2N0M0) underwent surgery (n=152), radiotherapy (n=20) and PDT (n=30) from 2000 to 2013 The KPS score, the disease-free survival (DFS), overall survival (OS), local control (LC), larynx preservation rate, laryngeal function were evaluated. The methods of chi (2)test or Fisher's exact probability method, Kaplan Meier method, log-rank test of Kaplan-Meier method, Cox proportional hazards model were used to analyze the data. RESULTS: There was no statistical significance in OS, DFS and LC among the three groups. The laryngeal function preservation rate of RT group, PDT group and Surgery group were 90%, 86.7% and 65.1% respectively, with the former two groups significantly superior to Surgery group. While there is no statistical significance between RT group and PDT group. Single factor analysis showed that KPS score before treatment, vocal fold mobility limitation and differentiation degree could have an effect on prognosis. Multivariate regression analyses indicated that anterior commissure invasion, T stage and KPS score before treatment were independent adverse prognostic factors for OS. T stage and differentiation degree were adverse prognostic factors for DFS. T stage was also an adverse factor of LC. Thirty-three cases experienced local recurrence or cervical lymph node metastasis. Three groups showed no statistical difference in local recurrence or lymph node metastasis, with twenty-two cases in Surgery group, four in RT group and seven in PDT group. CONCLUSIONS: The therapeutic effect was approximate in surgery group, radiotherapy group and photodynamic group, and all three treatment regimens achieved good clinical effect. Radiotherapy and photodynamic therapy may be the first or very important treatment on early stage glottic squamous cell cancer (Tis~T2N0M0). However only 6 patients underwent PDT for T2 disease, making definitive treatment conclusions for this subgroup unclear. PMID- 27378676 TI - Sinusology. AB - This paper presents a brief history of the successive anatomical, physiological and pathophysiological concepts about the paranasal sinuses. Sinusology, the science of the paranasal sinuses, is founded on scientific work on the production of nitric oxide (NO) by the sinuses and on the evo-devo theory of their formation. The paranasal sinuses seem to develop after regression of the erythropoietic marrow in the maxillary, frontal and sphenoid bones and its replacement by cavities filled with gas, which escapes into the nasal fossae through the ostium. The sinus epithelium synthesizes NO continuously. The paranasal sinus cavities form a compartmentalized reservoir of NO, which is released discontinuously in boli after an opening of the ostium. Ostium opening can be induced by sound vibration, either internal (humming) or external (an acoustic vibration added to the in-breath). NO plays the role of an "aerocrine" messenger between the upper and lower respiratory tracts, reducing pulmonary vascular resistance and facilitating alveolar oxygen transfer into the bloodstream. Its physiological role in arterial blood oxygenation could be involved in speech and singing or be activated by physiological snoring during sleep. Rhinology, the science of the nose, in which the evo-devo concept distinguishes the respiratory and the olfactory nose, is now backed up by sinusology. PMID- 27378677 TI - Reduced Burst Release and Enhanced Oral Bioavailability in Shikimic Acid-Loaded Polylactic Acid Submicron Particles by Coaxial Electrospray. AB - In this study, using the coaxial electrospray method, we prepared submicron particles of the water-soluble drug shikimic acid (SA) with polylactic acid (PLA) as a polymer, to reduce the burst release and enhance the oral bioavailability. In vitro release study performed in HCl solution (pH 1.2) showed that the coaxial electrospray submicron particles could reduce burst release effect and presented a sustained release profile, compared with free SA and the particles prepared by electrospray method. The absorption of SA in the intestinal tract, studied using an in situ perfusion method in rats, also revealed jejunum as the main absorptive segment followed by duodenum and ileum. Moreover, the SA-loaded particles greatly enhanced the absorption of SA in the tested intestinal segments. The intestinal absorption rate was not enhanced with increasing drug concentration (5-15 MUg/mL) which suggested that active transport or facilitated diffusion could play vital role in SA absorption. In addition, the SA-loaded PLA coaxial electrospray particle exhibited a prolonged plasma circulation with enhanced bioavailability after oral administration. In all, the coaxial electrospray technique could provide notable advantages for the oral delivery of SA, thereby enhancing its clinical application. PMID- 27378678 TI - Subcutaneous Injection Volume of Biopharmaceuticals-Pushing the Boundaries. AB - Administration into the subcutaneous (SC) tissue is a typical route of delivery for therapeutic proteins, especially for frequent treatments, long-term regimens, or self-administration. It is currently believed that the maximum volume for SC injections is approximately 1.5 mL. Larger SC injection volumes are considered to be associated with injection pain and adverse events at the injection site. However, no controlled clinical studies and actual evidence exist to support this assumption. In this review, we discuss current and publically available data related to SC administration volumes. We conclude that injection volumes higher than 3.5 mL are worth exploring if required for the development of efficacious drug treatments. Studying tissue back pressure, injection site leakage, local tolerability, and injection-related adverse events, such as injection pain, should be considered for the development of higher SC injection volumes. PMID- 27378679 TI - Sitting at patients' bedsides may improve patients' perceptions of physician communication skills. AB - Sitting at a patient's bedside in the inpatient setting is recommended as a best practice but has not been widely adopted. Previous studies suggest that a physician's seated posture may increase the patient's perception of time spent in the room but have not included hospitalists. We performed a cluster-randomized trial of seated versus standing physician posture during inpatient rounds on a hospitalist service at an academic medical center. Patients whose physician sat were significantly more likely to rate their physician highly on measures of listening carefully and explaining things in a way that was easy to understand. The average time spent in the patient's room was approximately 12 minutes and was not affected by physician posture. Patients' perception of the time their physician spent in their room was not affected by physician posture. Sitting at the bedside during rounds does not increase the amount of time spent with the patient but may improve patient-physician communication. Journal of Hospital Medicine 2015;11:865-868. (c) 2015 Society of Hospital Medicine. PMID- 27378680 TI - Early Recognition of Proteus Syndrome. AB - Proteus syndrome is an extremely rare mosaic condition characterized by progressive overgrowth of tissues due to a somatic activating mutation of the AKT1 gene. Distinct cutaneous features, including cerebriform connective tissue nevi, epidermal nevi, vascular malformations, and adipose abnormalities, can alert the dermatologist to the underlying condition before the onset of asymmetric skeletal overgrowth. We present a series of photographs documenting the skin and musculoskeletal changes in a patient with Proteus syndrome over the first 2 years of life to emphasize the key signs that a dermatologist can recognize to facilitate an earlier diagnosis in these patients. PMID- 27378681 TI - Polio infrastructure strengthened disease outbreak preparedness and response in the WHO African Region. AB - INTRODUCTION: The continuous deployments of polio resources, infrastructures and systems for responding to other disease outbreaks in many African countries has led to a number of lessons considered as best practice that need to be documented for strengthening preparedness and response activities in future outbreaks. METHODS: We reviewed and documented the influence of polio best practices in outbreak preparedness and response in Angola, Nigeria and Ethiopia. Data from relevant programmes of the WHO African Region were also analyzed to demonstrate clearly the relative contributions of PEI resources and infrastructure to effective disease outbreak preparedness and response. RESULTS: Polio resources including, human, financial, and logistic, tool and strategies have tremendously contributed to responding to diseases outbreaks across the African region. In Angola, Nigeria and Ethiopia, many disease epidemics including Marburg Hemorrhagic fever, Dengue fever, Ebola Virus Diseases (EVD), Measles, Anthrax and Shigella have been controlled using existing polio Eradication Initiatives resources. Polio staffs are usually deployed in occasions to supports outbreak response activities (coordination, surveillance, contact tracing, case investigation, finance, data management, etc.). Polio logistics such vehicles, laboratories were also used in the response activities to other infectious diseases. Many polio tools including micro planning, dashboard, guidelines, SOPs on preparedness and response have also benefited to other epidemic-prone diseases. The Countries' preparedness and response plan to WPV importation as well as the Polio Emergency Operation Center models were successfully used to develop, strengthen and respond to many other diseases outbreak with the implication of partners and the strong leadership and ownership of governments. This review has important implications for WHO/AFRO initiative to strengthening and improving disease outbreak preparedness and responses in the African Region in respect to the international health regulations core capacities. PMID- 27378682 TI - Editorial. PMID- 27378684 TI - GPs should have direct access to wider range of tests for suspected cancer, says NICE. PMID- 27378685 TI - Chitotriosidase as a novel biomarker of early atherosclerosis in hemodialysis patients. AB - INTRODUCTION: Increasing evidence suggests that inflammation and increased macrophage activity have a central role in pathogenesis of atherosclerosis. It is shown that chitotriosidase (CHIT-1) is a marker of macrophage activity in atherosclerotic plaque, and is found associated with severity of atherosclerotic lesion. There is no data about CHIT-1 activity of hemodialysis patients in the literature. Thus, we hypothesized that in hemodialysis patients, CHIT-1 levels might be a novel biomarker in early atherosclerosis. METHODS: Forty-five hemodialysis patients were included in the study (age: 61.93 +/- 13.34). Intima media thickness (IMT) was evaluated with high-resolution B-mode ultrasonography. Biomarker levels were measured in serum of patients. FINDINGS: We found positive correlation among IMT, age (R: 0.426, P: 0.004) and, CHIT-1 value (R: 0.462, P: 0.001) in spearman correlation analysis. When age, CRP, creatinine, P, Alb, CHIT 1 were chosen as measures that can effect IMT in multiple regression model, IMT level was related with CHIT-1 (Beta: 0,396, P: 0.012) and age (Beta: 0,313 P: 0,048) independently. DISCUSSION: In conclusion, this is the first report showing that serum CHIT-1 level was related independently with carotid IMT in hemodialysis patients. This biomarker might have an unknown role in the development of atherosclerosis during uremia. PMID- 27378686 TI - Antisense pre-treatment increases gene therapy efficacy in dystrophic muscles. AB - In preclinical models for Duchenne muscular dystrophy, dystrophin restoration during adeno-associated virus (AAV)-U7-mediated exon-skipping therapy was shown to decrease drastically after six months in treated muscles. This decline in efficacy is strongly correlated with the loss of the therapeutic AAV genomes, probably due to alterations of the dystrophic myofiber membranes. To improve the membrane integrity of the dystrophic myofibers at the time of AAV-U7 injection, mdx muscles were pre-treated with a single dose of the peptide-phosphorodiamidate morpholino (PPMO) antisense oligonucleotides that induced temporary dystrophin expression at the sarcolemma. The PPMO pre-treatment allowed efficient maintenance of AAV genomes in mdx muscles and enhanced the AAV-U7 therapy effect with a ten-fold increase of the protein level after 6 months. PPMO pre-treatment was also beneficial to AAV-mediated gene therapy with transfer of micro dystrophin cDNA into muscles. Therefore, avoiding vector genome loss after AAV injection by PPMO pre-treatment would allow efficient long-term restoration of dystrophin and the use of lower and thus safer vector doses for Duchenne patients. PMID- 27378688 TI - Identification of plexin A4 as a novel clusterin receptor links two Alzheimer's disease risk genes. AB - Although abundant genetic and biochemical evidence strongly links Clusterin (CLU) to Alzheimer disease (AD) pathogenesis, the receptor for CLU within the adult brain is currently unknown. Using unbiased approaches, we identified Plexin A4 (PLXNA4) as a novel, high-affinity receptor for CLU in the adult brain. PLXNA4 protein expression was high in brain with much lower levels in peripheral organs. CLU protein levels were significantly elevated in the cerebrospinal fluid (CSF) of Plxna4-/- mice and, in humans, CSF levels of CLU were also associated with PLXNA4 genotype. Human AD brains had significantly increased the levels of CLU protein but decreased levels of PLXNA4 by ~50%. To determine whether PLXNA4 levels influenced cognition, we analyzed the behaviour of Plxna4+/+, Plxna4+/-, and Plxna4-/- mice. In comparison to WT controls, both Plxna4+/- and Plxna4-/- mice were hyperactive in the open field assay while Plxna4-/- mice displayed a hyper-exploratory (low-anxiety phenotype) in the elevated plus maze. Importantly, both Plxna4+/- and Plxna4-/- mice displayed prominent deficits in learning and memory in the contextual fear-conditioning paradigm. Thus, even a 50% reduction in the level of PLXNA4 is sufficient to cause memory impairments, raising the possibility that memory problems seen in AD patients could be due to reductions in the level of PLXNA4. Both CLU and PLXNA4 have been genetically associated with AD risk and our data thus provide a direct relationship between two AD risk genes. Our data suggest that increasing the levels of PLXNA4 or targeting CLU PLXNA4 interactions may have therapeutic value in AD. PMID- 27378687 TI - Genetic ablation of IP3 receptor 2 increases cytokines and decreases survival of SOD1G93A mice. AB - Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease characterized by the selective death of motor neurons. Disease pathophysiology is complex and not yet fully understood. Higher gene expression of the inositol 1,4,5-trisphosphate receptor 2 gene (ITPR2), encoding the IP3 receptor 2 (IP3R2), was detected in sporadic ALS patients. Here, we demonstrate that IP3R2 gene expression was also increased in spinal cords of ALS mice. Moreover, an increase of IP3R2 expression was observed in other models of chronic and acute neurodegeneration. Upregulation of IP3R2 gene expression could be induced by lipopolysaccharide (LPS) in murine astrocytes, murine macrophages and human fibroblasts indicating that it may be a compensatory response to inflammation. Preventing this response by genetic deletion of ITPR2 from SOD1G93A mice had a dose-dependent effect on disease duration, resulting in a significantly shorter lifespan of these mice. In addition, the absence of IP3R2 led to increased innate immunity, which may contribute to the decreased survival of the SOD1G93A mice. Besides systemic inflammation, IP3R2 knockout mice also had increased IFNgamma, IL-6 and IL1alpha expression. Altogether, our data indicate that IP3R2 protects against the negative effects of inflammation, suggesting that the increase in IP3R2 expression in ALS patients is a protective response. PMID- 27378689 TI - Ectodysplasin signalling deficiency in mouse models of hypohidrotic ectodermal dysplasia leads to middle ear and nasal pathology. AB - Hypohidrotic ectodermal dysplasia (HED) results from mutation of the EDA, EDAR or EDARADD genes and is characterized by reduced or absent eccrine sweat glands, hair follicles and teeth, and defective formation of salivary, mammary and craniofacial glands. Mouse models with HED also carry Eda, Edar or Edaradd mutations and have defects that map to the same structures. Patients with HED have ear, nose and throat disease, but this has not been investigated in mice bearing comparable genetic mutations. We report that otitis media, rhinitis and nasopharyngitis occur at high frequency in Eda and Edar mutant mice and explore the pathogenic mechanisms related to glandular function, microbial and immune parameters in these lines. Nasopharynx auditory tube glands fail to develop in HED mutant mice and the functional implications include loss of lysozyme secretion, reduced mucociliary clearance and overgrowth of nasal commensal bacteria accompanied by neutrophil exudation. Heavy nasopharynx foreign body load and loss of gland protection alters the auditory tube gating function and the auditory tubes can become pathologically dilated. Accumulation of large foreign body particles in the bulla stimulates granuloma formation. Analysis of immune cell populations and myeloid cell function shows no evidence of overt immune deficiency in HED mutant mice. Our findings using HED mutant mice as a model for the human condition support the idea that ear and nose pathology in HED patients arises as a result of nasal and nasopharyngeal gland deficits, reduced mucociliary clearance and impaired auditory tube gating function underlies the pathological sequelae in the bulla. PMID- 27378690 TI - Reduction of TMEM97 increases NPC1 protein levels and restores cholesterol trafficking in Niemann-pick type C1 disease cells. AB - Niemann-Pick type C disease (NP-C) is a progressive lysosomal lipid storage disease caused by mutations in the NPC1 and NPC2 genes. NPC1 is essential for transporting cholesterol and other lipids out of lysosomes, but little is known about the mechanisms that control its cellular abundance and localization. Here we show that a reduction of TMEM97, a cholesterol-responsive NPC1-binding protein, increases NPC1 levels in cells through a post-transcriptional mechanism. Reducing TMEM97 through RNA-interference reduces lysosomal lipid storage and restores cholesterol trafficking to the endoplasmic reticulum in cell models of NP-C. In TMEM97 knockdown cells, NPC1 levels can be reinstated with wild type TMEM97, but not TMEM97 missing an ER-retention signal suggesting that TMEM97 contributes to controlling the availability of NPC1 to the cell. Importantly, knockdown of TMEM97 also increases levels of residual NPC1 in NPC1-mutant patient fibroblasts and reduces cholesterol storage in an NPC1-dependent manner. Our findings propose TMEM97 inhibition as a novel strategy to increase residual NPC1 levels in cells and a potential therapeutic target for NP-C. PMID- 27378691 TI - Long-range regulators of the lncRNA HOTAIR enhance its prognostic potential in breast cancer. AB - Predicting response to endocrine therapy and survival in oestrogen receptor positive breast cancer is a significant clinical challenge and novel prognostic biomarkers are needed. Long-range regulators of gene expression are emerging as promising biomarkers and therapeutic targets for human diseases, so we have explored the potential of distal enhancer elements of non-coding RNAs in the prognostication of breast cancer survival. HOTAIR is a long non-coding RNA that is overexpressed, promotes metastasis and is predictive of decreased survival. Here, we describe a long-range transcriptional enhancer of the HOTAIR gene that binds several hormone receptors and associated transcription factors, interacts with the HOTAIR promoter and augments transcription. This enhancer is dependent on Forkhead-Box transcription factors and functionally interacts with a novel alternate HOTAIR promoter. HOTAIR expression is negatively regulated by oestrogen, positively regulated by FOXA1 and FOXM1, and is inversely correlated with oestrogen receptor and directly correlated with FOXM1 in breast tumours. The combination of HOTAIR and FOXM1 enables greater discrimination of endocrine therapy responders and non-responders in patients with oestrogen receptor positive breast cancer. Consistent with this, HOTAIR expression is increased in cell-line models of endocrine resistance. Analysis of breast cancer gene expression data indicates that HOTAIR is co-expressed with FOXA1 and FOXM1 in HER2-enriched tumours, and these factors enhance the prognostic power of HOTAIR in aggressive HER2+ breast tumours. Our study elucidates the transcriptional regulation of HOTAIR, identifies HOTAIR and its regulators as novel biomarkers of patient response to endocrine therapy and corroborates the importance of transcriptional enhancers in cancer. PMID- 27378693 TI - Dystrophin contains multiple independent membrane-binding domains. AB - Dystrophin is a large sub-sarcolemmal protein. Its absence leads to Duchenne muscular dystrophy (DMD). Binding to the sarcolemma is essential for dystrophin to protect muscle from contraction-induced injury. It has long been thought that membrane binding of dystrophin depends on its cysteine-rich (CR) domain. Here, we provide in vivo evidence suggesting that dystrophin contains three additional membrane-binding domains including spectrin-like repeats (R)1-3, R10-12 and C terminus (CT). To systematically study dystrophin membrane binding, we split full length dystrophin into ten fragments and examined subcellular localizations of each fragment by adeno-associated virus-mediated gene transfer. In skeletal muscle, R1-3, CR domain and CT were exclusively localized at the sarcolemma. R10 12 showed both cytosolic and sarcolemmal localization. Importantly, the CR independent membrane binding was conserved in murine and canine muscles. A critical function of the CR-mediated membrane interaction is the assembly of the dystrophin-associated glycoprotein complex (DGC). While R1-3 and R10-12 did not restore the DGC, surprisingly, CT alone was sufficient to establish the DGC at the sarcolemma. Additional studies suggest that R1-3 and CT also bind to the sarcolemma in the heart, though relatively weak. Taken together, our study provides the first conclusive in vivo evidence that dystrophin contains multiple independent membrane-binding domains. These structurally and functionally distinctive membrane-binding domains provide a molecular framework for dystrophin to function as a shock absorber and signaling hub. Our results not only shed critical light on dystrophin biology and DMD pathogenesis, but also provide a foundation for rationally engineering minimized dystrophins for DMD gene therapy. PMID- 27378692 TI - A recurrent p.Arg92Trp variant in steroidogenic factor-1 (NR5A1) can act as a molecular switch in human sex development. AB - Cell lineages of the early human gonad commit to one of the two mutually antagonistic organogenetic fates, the testis or the ovary. Some individuals with a 46,XX karyotype develop testes or ovotestes (testicular or ovotesticular disorder of sex development; TDSD/OTDSD), due to the presence of the testis determining gene, SRY Other rare complex syndromic forms of TDSD/OTDSD are associated with mutations in pro-ovarian genes that repress testis development (e.g. WNT4); however, the genetic cause of the more common non-syndromic forms is unknown. Steroidogenic factor-1 (known as NR5A1) is a key regulator of reproductive development and function. Loss-of-function changes in NR5A1 in 46,XY individuals are associated with a spectrum of phenotypes in humans ranging from a lack of testis formation to male infertility. Mutations in NR5A1 in 46,XX women are associated with primary ovarian insufficiency, which includes a lack of ovary formation, primary and secondary amenorrhoea as well as early menopause. Here, we show that a specific recurrent heterozygous missense mutation (p.Arg92Trp) in the accessory DNA-binding region of NR5A1 is associated with variable degree of testis development in 46,XX children and adults from four unrelated families. Remarkably, in one family a sibling raised as a girl and carrying this NR5A1 mutation was found to have a 46,XY karyotype with partial testicular dysgenesis. These unique findings highlight how a specific variant in a developmental transcription factor can switch organ fate from the ovary to testis in mammals and represents the first missense mutation causing isolated, non-syndromic 46,XX testicular/ovotesticular DSD in humans. PMID- 27378694 TI - An enhanced Q175 knock-in mouse model of Huntington disease with higher mutant huntingtin levels and accelerated disease phenotypes. AB - Huntington disease (HD) model mice with heterozygous knock-in (KI) of an expanded CAG tract in exon 1 of the mouse huntingtin (Htt) gene homolog genetically recapitulate the mutation that causes HD, and might be favoured for preclinical studies. However, historically these mice have failed to phenotypically recapitulate the human disease. Thus, homozygous KI mice, which lack wildtype Htt, and are much less relevant to human HD, have been used. The zQ175 model was the first KI mouse to exhibit significant HD-like phenotypes when heterozygous. In an effort to exacerbate HD-like phenotypes and enhance preclinical utility, we have backcrossed zQ175 mice to FVB/N, a strain highly susceptible to neurodegeneration. These Q175F mice display significant HD-like phenotypes along with sudden early death from fatal seizures. The zQ175 KI allele retains a floxed neomycin resistance cassette upstream of the Htt gene locus and produces dramatically reduced mutant Htt as compared to the endogenous wildtype Htt allele. By intercrossing with mice expressing cre in germ line cells, we have excised the neo cassette from Q175F mice generating a new line, Q175FDeltaneo (Q175FDN). Removal of the neo cassette resulted in a ~2 fold increase in mutant Htt and rescue of fatal seizures, indicating that the early death phenotype of Q175F mice is caused by Htt deficiency rather than by mutant Htt. Additionally, Q175FDN mice exhibit earlier onset and a greater variety and severity of HD-like phenotypes than Q175F mice or any previously reported KI HD mouse model, making them valuable for preclinical studies. PMID- 27378696 TI - LRRK2 modulates microglial activity through regulation of chemokine (C-X3-C) receptor 1 -mediated signalling pathways. AB - Multiple missense mutations in Leucine-rich repeat kinase 2 (LRRK2) have been linked to Parkinson's disease (PD), the most common degenerative movement disorder. LRRK2 is expressed by both neurons and microglia, the residential immune cells in the brain. Increasing evidence supports a role of LRRK2 in modulating microglial activity, of which Lrrk2-null rodent microglia display less inflammatory response to endotoxin lipopolysaccharide (LPS). The underlying molecular mechanism, however, remains elusive. Chemokine (C-X3-C) receptor 1 (CX3CR1), predominantly expressed by microglia, suppresses microglial inflammation while promotes migration. Using whole-genome microarray screening, we found that Cx3cr1 mRNA levels were substantially higher in microglia derived from Lrrk2 knockout (Lrrk2-/-) mice. The total and cell surface levels of CX3CR1 proteins were also remarkably increased. In correlation with the enhanced CX3CR1 expression, Lrrk2-null microglia migrated faster and travelled longer distance toward the source of fractalkine (CX3CL1), an endogenous ligand of CX3CR1. To investigate the impact of CX3CR1 elevation in vivo, we compared LPS-induced inflammation in the striatum of Lrrk2-/- knockout mice with Cx3cr1 heterozygous and homozygous knockout background. We found that a complete loss of Cx3cr1 restored the responsiveness of Lrrk2-/- microglia to LPS stimulation. In conclusion, our findings reveal a previously unknown regulatory role for LRRK2 in CX3CR1 signalling and suggest that an increase of CX3CR1 activity contributes to the attenuated inflammatory responses in Lrrk2-null microglia. PMID- 27378697 TI - Sustained expression of FMR1 mRNA from reactivated fragile X syndrome alleles after treatment with small molecules that prevent trimethylation of H3K27. AB - Expansion of a CGG-repeat tract in the 5'-untranslated region of the FMR1 gene to >200 repeats results in epigenetic silencing of the gene by a mechanism that is still unknown. FMR1 gene silencing results in fragile X syndrome (FXS), the most common heritable cause of intellectual disability. We have previously shown that reactivation of the FMR1 gene in FXS cells with 5-azadeoxycytidine (AZA) leads to the transient recruitment of EZH2, the polycomb repressive complex 2 (PRC2) component responsible for H3K27 trimethylation, and that this recruitment depends on the presence of the FMR1 transcript. However, whether H3K27 trimethylation was essential for FMR1 re-silencing was not known. We show here that EZH2 inhibitors increased FMR1 expression and significantly delayed re-silencing of the FMR1 gene in AZA-treated FXS cells. This delay occurred despite the fact that EZH2 inhibition did not prevent the return of DNA methylation. Treatment with compound 1a, a small molecule that targets CGG-repeats in the FMR1 mRNA, also resulted in sustained expression of the FMR1 gene in AZA-treated cells. This effect of 1a was also associated with a decrease in the levels of H3K27 trimethylation but not DNA methylation. Thus, our data show that EZH2 plays a critical role in the FMR1 gene silencing process and that its inhibition can prolong expression of the FMR1 gene even in the presence of its transcript. PMID- 27378698 TI - Autophagic lysosome reformation dysfunction in glucocerebrosidase deficient cells: relevance to Parkinson disease. AB - Glucocerebrosidase (GBA1) gene mutations increase the risk of Parkinson disease (PD). While the cellular mechanisms associating GBA1 mutations and PD are unknown, loss of the glucocerebrosidase enzyme (GCase) activity, inhibition of autophagy and increased alpha-synuclein levels have been implicated. Here we show that autophagy lysosomal reformation (ALR) is compromised in cells lacking functional GCase. ALR is a cellular process controlled by mTOR which regenerates functional lysosomes from autolysosomes formed during macroautophagy. A decrease in phopho-S6K levels, a marker of mTOR activity, was observed in models of GCase deficiency, including primary mouse neurons and the PD patient derived fibroblasts with GBA1 mutations, suggesting that ALR is compromised. Importantly Rab7, a GTPase crucial for endosome-lysosome trafficking and ALR, accumulated in GCase deficient cells, supporting the notion that lysosomal recycling is impaired. Recombinant GCase treatment reversed ALR inhibition and lysosomal dysfunction. Moreover, ALR dysfunction was accompanied by impairment of macroautophagy and chaperone-mediated autophagy, increased levels of total and phosphorylated (S129) monomeric alpha-synuclein, evidence of amyloid oligomers and increased alpha-synuclein release. Concurrently, we found increased cholesterol and altered glucosylceramide homeostasis which could compromise ALR. We propose that GCase deficiency in PD inhibits lysosomal recycling. Consequently neurons are unable to maintain the pool of mature and functional lysosomes required for the autophagic clearance of alpha-synuclein, leading to the accumulation and spread of pathogenic alpha-synuclein species in the brain. Since GCase deficiency and lysosomal dysfunction occur with ageing and sporadic PD pathology, the decrease in lysosomal reformation may be a common feature in PD. PMID- 27378695 TI - Exome genotyping arrays to identify rare and low frequency variants associated with epithelial ovarian cancer risk. AB - Rare and low frequency variants are not well covered in most germline genotyping arrays and are understudied in relation to epithelial ovarian cancer (EOC) risk. To address this gap, we used genotyping arrays targeting rarer protein-coding variation in 8,165 EOC cases and 11,619 controls from the international Ovarian Cancer Association Consortium (OCAC). Pooled association analyses were conducted at the variant and gene level for 98,543 variants directly genotyped through two exome genotyping projects. Only common variants that represent or are in strong linkage disequilibrium (LD) with previously-identified signals at established loci reached traditional thresholds for exome-wide significance (P < 5.0 * 10 - 7). One of the most significant signals (Pall histologies = 1.01 * 10 - 13;Pserous = 3.54 * 10 - 14) occurred at 3q25.31 for rs62273959, a missense variant mapping to the LEKR1 gene that is in LD (r2 = 0.90) with a previously identified 'best hit' (rs7651446) mapping to an intron of TIPARP. Suggestive associations (5.0 * 10 - 5 > P>=5.0 *10 - 7) were detected for rare and low frequency variants at 16 novel loci. Four rare missense variants were identified (ACTBL2 rs73757391 (5q11.2), BTD rs200337373 (3p25.1), KRT13 rs150321809 (17q21.2) and MC2R rs104894658 (18p11.21)), but only MC2R rs104894668 had a large effect size (OR = 9.66). Genes most strongly associated with EOC risk included ACTBL2 (PAML = 3.23 * 10 - 5; PSKAT-o = 9.23 * 10 - 4) and KRT13 (PAML = 1.67 * 10 - 4; PSKAT-o = 1.07 * 10 - 5), reaffirming variant-level analysis. In summary, this large study identified several rare and low-frequency variants and genes that may contribute to EOC susceptibility, albeit with possible small effects. Future studies that integrate epidemiology, sequencing, and functional assays are needed to further unravel the unexplained heritability and biology of this disease. PMID- 27378700 TI - Surface functionality affects the biodistribution and microglia-targeting of intra-amniotically delivered dendrimers. AB - Cerebral Palsy (CP) is a chronic childhood disorder with limited therapeutic options. Maternal intrauterine inflammation/infection is a major risk factor in the pathogenesis of CP. In pre-clinical models, dendrimer-based therapies are viable in postnatal period, attenuating inflammation and improving motor function in vivo. However, treatment to the mother, in the prenatal period, may provide the possibility of preventing/resolving inflammation at early stages. Towards this goal, we used a maternal intrauterine inflammation-induced rabbit model of CP to study fetal-maternal transport and neuroinflammation targeting of intra amniotically administrated dendrimers with neutral/anionic surface functionality. Our study suggested both hydroxyl-terminated 'neutral' (D-OH) and carboxyl terminated 'anionic' (D-COOH) Polyamidoamine (PAMAM) dendrimers were absorbed by fetuses and demonstrated bi-directional transport between fetuses and mother. D OH was more effective in crossing the fetal blood-brain barrier, and targeting activated microglia. The cell-specific targeting was associated with the extent of microglia activation. This study demonstrated intra-amniotically administered hydroxyl PAMAM dendrimers could be an effective drug delivery vehicle for targeting fetal inflammation and preventing subsequent neurologic injury associated with chorioamnionitis. PMID- 27378701 TI - A novel method of using accelerometry for upper limb FES control. AB - This paper reports on a novel approach to using a 3-axis accelerometer to capture body segment angle for upper limb functional electrical stimulation (FES) control. The approach calculates the angle between the accelerometer x-axis and the gravity vector, while avoiding poor sensitivity at certain angles and minimizing errors when true acceleration is relatively large in comparison to gravity. This approach was incorporated into a state-machine controller which is used for the real-time control of FES during upper limb functional task performance. An experimental approach was used to validate the new method. Two participants with different upper limb impairments resulting from a stroke carried out four different FES-assisted tasks. Comparisons were made between angle calculated from arm-mounted accelerometer data using our algorithm and angle calculated from limb-mounted reflective marker data. After removal of coordinate misalignment error, mean error across tasks and subjects ranged between 1.4 and 2.9 degrees . The approach shows promise for use in the control of upper limb FES and other human movement applications where true acceleration is relatively small in comparison with gravity. PMID- 27378699 TI - Transcriptome sequencing reveals aberrant alternative splicing in Huntington's disease. AB - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG expansion in the gene-encoding Huntingtin (HTT). Transcriptome dysregulation is a major feature of HD pathogenesis, as revealed by a large body of work on gene expression profiling of tissues from human HD patients and mouse models. These studies were primarily focused on transcriptional changes affecting steady-state overall gene expression levels using microarray based approaches. A major missing component, however, has been the study of transcriptome changes at the post-transcriptional level, such as alternative splicing. Alternative splicing is a critical mechanism for expanding regulatory and functional diversity from a limited number of genes, and is particularly complex in the mammalian brain. Here we carried out a deep RNA-seq analysis of the BA4 (Brodmann area 4) motor cortex from seven human HD brains and seven controls to systematically discover aberrant alternative splicing events and characterize potential associated splicing factors in HD. We identified 593 differential alternative splicing events between HD and control brains. Using two expanded panels with a total of 108 BA4 tissues from patients and controls, we identified four splicing factors exhibiting significantly altered expression levels in HD patient brains. Moreover, follow-up molecular analyses of one splicing factor PTBP1 revealed its impact on disease-associated splicing patterns in HD. Collectively, our data provide genomic evidence for widespread splicing dysregulation in HD brains, and suggest the role of aberrant alternative splicing in the pathogenesis of HD. PMID- 27378702 TI - A thermoregulation model for hypothermic treatment of neonates. AB - This paper presents a thermoregulation finite element model (FEM) to simulate hypothermia procedures for the treatment of encephalopathy hypoxic-ischemia (EHI) in neonates, a dangerous ischemic condition that can cause neurological damages and even death. Therapeutic hypothermia is the only recommended technique to reduce sequels caused by EHI in neonates; intervention with moderate cooling for neural rescue in newborns with hypoxic-ischemic brain injury is the culmination of a series of clinical research studies spanning decades. However, the direct monitoring of brain cooling is difficult and can lead to additional tissue damage. Therefore, the measurement of efficiency during clinical trials of hypothermia treatment is still challenging. The use of computational methods can aid clinicians to observe the continuous temperature of tissues and organs during cooling procedures without the need for invasive techniques, and can thus be a valuable tool to assist clinical trials simulating different cooling options that can be used for treatment. The use of low cost methods such as cooling blankets can open the possibility of using brain cooling techniques in hospitals and clinics that cannot currently afford the available expensive equipment and techniques. In this work, we developed a FEM package using isoparametric linear three-dimensional elements which is applied to the solution of the continuum bioheat Pennes equation. Blood temperature changes were considered using a blood pool approach. The results of the FEM model were compared to those obtained through the implementation of a user-defined function (UDF) in the commercial finite volume software FLUENT and validated with experimental tests. Numerical analyses were performed using a three-dimensional mesh based on a complex geometry obtained from MRI scan medical images. PMID- 27378703 TI - Prescription drugs associated with false-positive results when using faecal immunochemical tests for colorectal cancer screening. AB - BACKGROUND: The most common side effect in population screening programmes is a false-positive result which leads to unnecessary risks and costs. AIMS: To identify factors associated with false-positive results in a colorectal cancer screening programme with the faecal immunochemical test (FIT). METHODS: Cross sectional study of 472 participants with a positive FIT who underwent colonoscopy for confirmation of diagnosis between 2013 and 2014. A false-positive result was defined as having a positive FIT (>=20MUg haemoglobin per gram of faeces) and follow-up colonoscopy without intermediate/high-risk lesions or cancer. RESULTS: Women showed a two-fold increased likelihood of a false-positive result compared with men (adjusted OR, 2.3; 95%CI, 1.5-3.4), but no female-specific factor was identified. The other variables associated with a false-positive result were successive screening (adjusted OR, 1.5; 95%CI, 1.0-2.2), anal disorders (adjusted OR, 3.1; 95%CI, 2.1-4.5) and the use of proton pump inhibitors (adjusted OR, 1.8; 95%CI, 1.1-2.9). Successive screening and proton pump inhibitor use were associated with FP in men. None of the other drugs were related to a false positive FIT. CONCLUSION: Concurrent use of proton pump inhibitors at the time of FIT might increase the likelihood of a false-positive result. Further investigation is needed to determine whether discontinuing them could decrease the false-positive rate. PMID- 27378705 TI - Patients with mild enteropathy have apoptotic injury of enterocytes similar to that in advanced enteropathy in celiac disease. AB - BACKGROUND: Severity of villous atrophy in celiac disease (CeD) is the cumulative effect of enterocyte loss and cell regeneration. Gluten-free diet has been shown to benefit even in patients having a positive anti-tissue transglutaminase (tTG) antibody titre and mild enteropathy. AIM: We explored the balance between mucosal apoptotic enterocyte loss and cell regeneration in mild and advanced enteropathies. METHODS: Duodenal biopsies from patients with mild enteropathy (Marsh grade 0 and 1) (n=26), advanced enteropathy (Marsh grade >=2) (n=41) and control biopsies (n=12) were subjected to immunohistochemical staining for end apoptotic markers (M30, H2AX); markers of cell death (perforin, annexin V); and cell proliferation (Ki67). Composite H-scores based on the intensity and distribution of markers were compared. RESULTS: End-apoptotic markers and marker of cell death (perforin) were significantly up-regulated in both mild and advanced enteropathies, in comparison to controls; without any difference between mild and advanced enteropathies. Ki67 labelling index was significantly higher in crypts of mild enteropathy, in comparison to controls, suggesting maintained regenerative activity in the former. CONCLUSIONS: Even in patients with mild enteropathy, the rate of apoptosis is similar to those with advanced enteropathy. These findings suggest the necessity of reviewing the existing practice of not treating patients with mild enteropathy. PMID- 27378704 TI - Comparison of paroxetine and amitriptyline in the treatment of refractory globus pharyngeus. AB - BACKGROUND: Clinical trials of antidepressants for treatment of globus are generally rare, let alone for refractory globus pharyngeus. AIMS: To illustrate the efficacy and side-effects of antidepressants between paroxetine and amitriptyline for refractory globus patients. METHODS: Refractory globus patients were randomized into paroxetine group; amitriptyline group and lansoprazole group for 6-week treatment. All the subjects were asked to complete the following questionnaires pre- and post-therapy: Glasgow Edinburgh Throat Scale (GETS), Pittsburgh Sleep Quality Index, Hamilton Rating Scale Anxiety/Depression and Medical outcome short-form 36. Treatment response was defined as a >50% reduction in the GETS score. RESULTS: One hundred and forty-eight patients completed the study. After 6 week treatment, 71.7% of paroxetine group (33/46) were calculated as treatment response, significantly higher than that in amitriptyline group (46.2%, 24/52) and lansoprazole group (14.0%, 7/50). Compared with lansoprazole group or amitriptyline group, a more distinct improvement of emotional well being, quality of life and quality of sleep were observed in paroxetine group after 6-week treatment. CONCLUSION: Paroxetine therapy is more efficacious than empirical high-dose antisecretory treatment, or even the low-dose amitriptyline therapy in alleviating globus symptoms, and producing global improvements for refractory globus patients. PMID- 27378706 TI - Low testosterone in non-responsive coeliac disease: A case series, case-control study with comparisons to the National Health and Nutrition Examination Survey. AB - BACKGROUND: Adults with coeliac disease (CD) often report persistent fatigue, even when CD appears well controlled for unknown reasons. AIMS: To evaluate common indications for testosterone panel (TP) testing and prevalence of low testosterone (T) in CD. METHODS: In our case series, we determined common indications for checking TP in CD. Next, we conducted a case-control study to compare TP in CD vs. healthy controls (HC). We compared mean total T (TT), free T (FT) based on serologic, histologic disease activity. Finally, we assessed TT in tissue transglutaminase (tTG)+ vs. tTG- subjects and CD vs. HC obtained from the National Health and Nutrition Examination Survey (NHANES). RESULTS: 53 coeliac males had TP tested. Common indications included osteoporosis and fatigue. Low FT was observed in 7/13 men with osteoporosis and 5/6 with fatigue. In our case control study (n=26 each), there was no difference in mean TT or FT between CD vs. HC, tTG+ vs tTG- or Marsh 0 vs. Marsh 3 groups. NHANES data showed no difference in mean TT between tTG+ vs tTG- (n=16 each) or CD vs. HC subjects (n=5 each). CONCLUSIONS: Low T occurs in CD patients at a similar rate as the general population. Common presentations of low T may mimic non-responsive CD symptoms. PMID- 27378707 TI - Predictive factors of poor response to therapy in Autoimmune Hepatitis. AB - AIM: To evaluate "ex ante" the predictive factors of incomplete/absent response to the standard therapy in a well characterized series of Autoimmune Hepatitis (AIH) patients from Italy. METHODS: Of 282 AIH patients screened from our database 166 (59%) had a sustained response and 116 (41%) had an incomplete/absent response to the therapy; all patients were analyzed for the clinical, serological and histological parameters at diagnosis. RESULTS: The patients with incomplete/absent response were characterized by significantly younger age (30 aa vs 42 aa p=0.001) and a significantly higher frequency of cirrhosis at diagnosis than patients who had a complete response to therapy (26% vs 3% p<0.0001); furthermore, patients with incomplete/absent response were distinguished from those with a complete response for significantly lower serum levels of both AST (7.9*upper normal limit [unl] vs 13*unl p<0.005) and ALT (10.9*unl vs 18*unl p=0.002) at diagnosis, and by an increase in IgG serum levels (1.43*unl vs 1.27*unl p=0.009). After stepwise logistic regression, cirrhosis at diagnosis (p=0.003, OR 0.12, 95% CI 0.03-0.49) and younger age (p=0.001, OR 1.03, 95% CI 1.01-1.05) represent two independent variables of incomplete/absent response. CONCLUSIONS: Younger age and cirrhosis are predictive of lack of response to the standard therapy in AIH patients. PMID- 27378708 TI - Enhanced recovery pathway for elective caesarean section. PMID- 27378709 TI - A retrospective review of an epidural blood patch database: the incidence of epidural blood patch associated with obstetric neuraxial anesthetic techniques and the effect of blood volume on efficacy. AB - BACKGROUND: The optimal volume of blood required to treat post-dural puncture headache remains in question. In our institution a target volume of 30mL is used for an epidural blood patch unless the patient experiences pain during injection. METHODS: The institutional database was retrospectively reviewed for epidural blood patch and delivery statistics over a 15-year period to determine if the volume of blood administered during the procedure directly correlated with the number of epidural blood patches administered. The primary endpoint was defined as the need for a repeat epidural blood patch. RESULTS: There were 466 epidural blood patches performed on 394 patients, associated with 84 804 obstetric neuraxial procedures. Thirty-two percent (95% CI 28.3 to 34.9%) of patients who had an inadvertent dural puncture with an epidural needle received an epidural blood patch versus 0.19% (0.16% to 0.22%) of patients who received neuraxial anesthesia with no documented dural puncture with an epidural needle. All patients experienced relief of post-dural puncture headache, although 17% required two and 1.5% required three epidural blood patches. The mean+/-SD volume of blood administered was 20.5+/-5.4mL and only 35 patients (8.9%) received 30mL. CONCLUSION: Increasing blood volumes up to 30mL did not reduce the need for repeat epidural blood patch. Although the optimal volume of blood to administer during epidural blood patch placement remains unknown, our institution will continue to administer up to 30mL or until the patient experiences pain during epidural injection. PMID- 27378710 TI - Anesthetic management of a parturient with Stiff person syndrome for urgent cesarean delivery. AB - Stiff person syndrome is a rare neurologic disorder with an estimated incidence of 1:1000000. The underlying pathophysiology is truncal and proximal limb muscle stiffness resulting from continuous co-contracture of agonist and antagonist muscle groups concomitant with superimposed episodic muscle spasms. Loss of gamma aminobutyric acid-mediated inhibition creates chronic excitation manifested by tonic agonist-antagonist muscle contraction. To date, only three case reports referred indirectly to the anesthetic management of parturients with Stiff person syndrome. The authors describe their management of a parturient with Stiff person syndrome who underwent urgent cesarean delivery under epidural anesthesia. PMID- 27378711 TI - Another look at religious objections to obstetric anaesthesia. AB - Starting with the earliest biographies of James Young Simpson, the topic of religious opposition to obstetric anaesthesia in 1847 was gradually embellished in historical articles. Objective data are lacking and it has been suggested that this is a myth of recent medical history. A search for more information led to a contemporaneous case-book of the maternity hospital in Edinburgh, which was examined. The provision of anaesthesia in the 11months before publication of Simpson's pamphlet Answer to the Religious Objections was compared with that in the 11months after. This revealed a marked increase (P<0.01) in the provision of anaesthesia for childbirth after the publication of Simpson's pamphlet in December 1847. This analysis supports the existence of opposition to obstetric anaesthesia and the success of Simpson's pamphlet in overcoming it, but the introduction of chloroform about six weeks earlier, may also have contributed. PMID- 27378712 TI - The changes of aortic diameter after aortic repair with aortic tailoring technique for chronic type B aortic dissection. AB - OBJECTIVES: Aortic repair with aortic tailoring of the false lumen can preserve the true lumen and intercostal arteries naturally. It is a useful surgical strategy to prevent paraplegia. However, aortic remodelling of tailored segments in a late phase after surgery is another concern. This study investigates the destiny of aortic remodelling of tailored aorta. METHODS: From June 2004 to April 2013, 21 consecutive patients underwent aortic tailoring operation for chronic type B aortic dissecting aneurysm. The mean age at operation was 60 +/- 10 years (range, 43-77). The tailored aortic segments were followed by serial CT scanning with the mean follow-up period of 46 +/- 32 months (range, 2-103). RESULTS: There were no operative deaths but paraplegia in 1, stroke in 1 and reversible renal failure in 2 patients. There were two late deaths: one due to pneumonia and the other due to aneurysmal rupture of the abdominal aorta. Eighteen patients revealed a completely thrombosed false lumen and no expansion of the tailored aorta, with it remaining less than 40 mm in diameter during follow-up. However, 3 cases were associated with a patent false lumen and 2 cases revealed aortic events. The aortic event-free rate at 5 years was 95 +/- 5.1% in all patients and 66 +/- 27% in patients in the patent false lumen group. CONCLUSIONS: Aortic tailoring is a useful surgical technique for chronic type B aortic dissection. Paraplegia and ischaemia of other visceral organs could less likely occur. Patients with a completely thrombosed false lumen revealed no aortic events; however, a patent false lumen was associated with a high risk of aortic events. PMID- 27378713 TI - Right ventricular and chest wall perforation caused by a permanent pacemaker lead after implantation. PMID- 27378714 TI - Precision Medicine an Interprofessional Science. PMID- 27378716 TI - What is your diagnosis? Liver aspirate from a cat. PMID- 27378715 TI - Renal recovery and long-term survival following acute kidney injury after coronary artery surgery: a nationwide study. AB - BACKGROUND: Acute kidney injury (AKI) is a relatively common complication following CABG and is associated with adverse outcomes. Nonetheless, we hypothesized that the majority of patients make a good long-term recovery of their renal function. We studied the incidence and risk factors of AKI together with renal recovery and long-term survival in patients who developed AKI following CABG. METHODS: This nationwide study examined AKI among 1754 consecutive patients undergoing CABG in 2001-2013. AKI was defined according to the KDIGO criteria. RESULTS: Postoperatively 184 (11%) patients developed AKI; 121 (7%), 27 (2%), and 36 (2%) at stages 1, 2, and 3, respectively. AKI was an independent risk factor for chronic kidney disease (CKD) and AKI patients had worse post-operative outcomes. Lower pre-operative glomerular filtration rate, higher EuroSCORE and BMI, diabetes, reoperation, and units of red blood cells transfused were independent risk factors of AKI. At post-operative day 10, renal recovery rates, defined as serum creatinine ratio <1.25 of baseline, were 96 (95% CI 91-99%), 78 (95% CI 53-90%), and 94% (95% CI 77-98%) for AKI stages 1, 2, and 3, respectively. Long-term survival was predicted by AKI with 10-year survival of patients without AKI being 76% and those with AKI stages 1, 2, and 3 being 63%, 56%, and 49%, respectively (P < 0.001). CONCLUSION: Depending on the severity of the initial AKI, 78-97% of patients made good recovery of their kidney function. However, AKI was significantly linked to progression to CKD and long-term survival remained markedly affected by the severity of the initial kidney injury. PMID- 27378717 TI - Health-related quality of life and its association with self-esteem and fatigue among children diagnosed with cancer. AB - AIMS AND OBJECTIVES: To identify the links between self-esteem, fatigue and health-related quality of life for children and young people during and following treatment for cancer. BACKGROUND: Measures to minimise adverse outcomes for survivors of childhood cancer have been developed, but the crucial periods of returning to school and transition to adult life and adult services are not addressed so well. Screening of quality of life, fatigue and self-esteem in childhood cancer patients during and after treatment is important for optimising the nursing response and improving outcomes for children. DESIGN: A cross sectional, descriptive, correlational, comparative survey was designed. METHODS: Validated measures of the attributes being studied were used. This study was conducted in private rooms on the ward and in the outpatient clinic of a major oncology hospital in Jordan in 2015. Seventy children aged 5-16 years were included. Ethical approval was secured. RESULTS: The age range of the children was 5-16 years (Mean 10.17, SD 3.4 years). Thirty were girls and 40 were boys. The total quality of life scores ranged from 21-100 (M = 65.5; SD = 17.6). The total scores of fatigue range from 12.5-100 (M = 65.79; SD = 22.20). Children with a high level of fatigue experienced lower quality of life. CONCLUSION: Continuing education centres at hospitals may find the results of this study helpful to provide professional updates and training events to enhance nurses' understanding of psychosocial distress responses and ability to intervene effectively within the multiprofessional effort. RELEVANCE TO CLINICAL PRACTICE: The outcomes of this study may enhance the development of guidelines for routine assessment by nurses and others of these factors among children with cancer. The nursing role in ensuring holistic care and attention to the problems of most concern to patients could be strengthened. PMID- 27378718 TI - Rape and Mental Health Outcomes Among Women: Examining the Moderating Effects of "Healthy" Fear Levels. AB - This study examined the mediating and moderating impact of fear of victimization on the relationships between forcible and vicarious rape on depression and post traumatic stress disorder (PTSD) among college women. Forcible and vicarious rape positively affected PTSD and depression symptomology, but fear did not mediate these relationships. Fear moderated the impact of forcible rape on PTSD, but was not a moderator for depression. Findings suggest that there may be "healthy" levels of fear in the aftermath of victimization where having too little fear may leave women unnecessarily vulnerable to victimization, while having too much fear may lead to social isolation and withdrawal. PMID- 27378719 TI - Gender Equality, Patriarchal Cultural Norms, and Perpetration of Intimate Partner Violence: Comparison of Male University Students in Asian and European Cultural Contexts. AB - This study examined the relationship between patriarchal cultural norms and violence perpetration by male partners using a subsample of university students in Asia ( n = 784) and Europe ( n = 575) from the International Dating Violence Study (IDVS) data set. Bivariate analyses indicated Asian students scored significantly higher than Europeans on dominance, hostility to women, jealousy, negative attribution, and violence approval as well as perpetration of severe physical assault in dating relationships. Logistic regression models demonstrated that dominance and violence approval were significant predictors of severe physical and psychological aggression against dating partners. Implications for culturally relevant programming for intimate partner violence prevention are discussed. PMID- 27378720 TI - "There Were Rapes!": Sexual Assaults of African American Women and Children in Jim Crow. AB - Using data from 92 interviews, this article examines the narratives of African Americans' experiences as children and young adults during Jim Crow in the Southeast and Southwest. It gives voice to the realities of sexual assaults committed by ordinary White men who systematically terrorized African American families with impunity after the post-Reconstruction south until the 1960s. The interviewees discuss the short- and long-term impact of physical, mental, emotional, and sexual assaults in their communities. We discuss the top four prevalent themes that emerged related to sexual assault, specifically (a) the normalization of sexual assaults, (b) protective measures to avoid White violence, (c) the morality of African American women, and (d) the long-term consequences of assaults on children. PMID- 27378722 TI - GP is suspended for three months for smacking hand of patient with dementia. PMID- 27378721 TI - Logistic regression analysis of Pierre Robin sequence patients requiring surgical intervention. AB - OBJECTIVES/HYPOTHESIS: Determine predictive patient characteristics that guide the decision to proceed with surgical management of tongue-based airway obstruction (TBAO) in Pierre Robin sequence (PRS) patients. STUDY DESIGN: Retrospective review of PRS patients between 2005 and 2014 requiring observation in the neonatal intensive care unit (NICU). METHODS: Patient charts were reviewed for prenatal diagnoses, clinical course, and need for surgical intervention (tracheotomy or mandibular distraction osteogenesis), and the nonsurgical and surgical group were compared with a logistic regression model. RESULTS: Thirty eight PRS patients who were identified with TBAO and required NICU observation had an average follow-up of 5.4 years. Associated anomalies identified in the PRS patients included neurologic disease (n = 6), renal abnormalities (n = 5), limb abnormalities (n = 4), and cardiac abnormalities (n = 12). Nonsurgical management of PRS TBAO included side (n = 12)/stomach positioning (n = 15), oral airway (n = 6), nasopharyngeal airway (NPA) (n = 14), and intubation (n = 12). Surgical intervention occurred in 13 patients, with tracheotomy in eight due to unstable airway, and mandible distraction in five due to NPA dependence. Factors with significant uncontrolled correlations with the need for surgical airways included presence of cardiac disease (P = .03), cardiac disease severity (P = .03), neurologic disease (P = .01), and continuous positive airway pressure (CPAP)/bilevel positive airway pressure (BiPAP) use (P = .006). Further, stepwise regression showed strong predictive value for CPAP/BiPAP use (odds ratio [OR]: 10.43) and presence of neurological disease (OR: 9.16). PRS TBAO patients required multiple modalities of noninvasive surgical intervention to stabilize their airway. CONCLUSIONS: This study identified patient characteristics predictive of progression to a surgical airway to address TBAO, which may decrease healthcare utilization and improve quality of life for these families. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:945-949, 2017. PMID- 27378723 TI - Malpractice in Cases of Pediatric Appendicitis. AB - Appendicitis is one of the most common diagnoses in children and is frequently the focus of alleged malpractice. Causes for medical malpractice claims and outcomes of disputes in pediatric patients with appendicitis are currently unknown. A retrospective database review of all medical malpractice claims concerning the diagnosis of appendicitis from 1984 to 2013 in pediatric patients was performed. Alleged claims, causes of malpractice, and outcomes were recorded and analyzed. Of the 203 included cases, failure or delays in diagnosing appendicitis are the most common causes of malpractice lawsuits and account for the majority of the largest payments to plaintiffs outcomes. Cases that ultimately went to trial resulted in defense verdicts in 67.5%. Mortality occurred in 19.9% of included cases. Timely diagnosis of appendicitis in children should be the focus of physicians across all specialties to improve patient safety and potentially reduce medicolegal liability. PMID- 27378724 TI - Effect of GR24 Stereoisomers on Plant Development in Arabidopsis. PMID- 27378725 TI - Functional Analysis of Semi-conserved Transit Peptide Motifs and Mechanistic Implications in Precursor Targeting and Recognition. AB - Over 95% of plastid proteins are nuclear-encoded as their precursors containing an N-terminal extension known as the transit peptide (TP). Although highly variable, TPs direct the precursors through a conserved, posttranslational mechanism involving translocons in the outer (TOC) and inner envelope (TOC). The organelle import specificity is mediated by one or more components of the Toc complex. However, the high TP diversity creates a paradox on how the sequences can be specifically recognized. An emerging model of TP design is that they contain multiple loosely conserved motifs that are recognized at different steps in the targeting and transport process. Bioinformatics has demonstrated that many TPs contain semi-conserved physicochemical motifs, termed FGLK. In order to characterize FGLK motifs in TP recognition and import, we have analyzed two well studied TPs from the precursor of RuBisCO small subunit (SStp) and ferredoxin (Fdtp). Both SStp and Fdtp contain two FGLK motifs. Analysis of large set mutations (~85) in these two motifs using in vitro, in organello, and in vivo approaches support a model in which the FGLK domains mediate interaction with TOC34 and possibly other TOC components. In vivo import analysis suggests that multiple FGLK motifs are functionally redundant. Furthermore, we discuss how FGLK motifs are required for efficient precursor protein import and how these elements may permit a convergent function of this highly variable class of targeting sequences. PMID- 27378726 TI - Shaping Small Bioactive Molecules to Untangle Their Biological Function: A Focus on Fluorescent Plant Hormones. AB - Modern biology overlaps with chemistry in explaining the structure and function of all cellular processes at the molecular level. Plant hormone research is perfectly located at the interface between these two disciplines, taking advantage of synthetic and computational chemistry as a tool to decipher the complex biological mechanisms regulating the action of plant hormones. These small signaling molecules regulate a wide range of developmental processes, adapting plant growth to ever changing environmental conditions. The synthesis of small bioactive molecules mimicking the activity of endogenous hormones allows us to unveil many molecular features of their functioning, giving rise to a new field, plant chemical biology. In this framework, fluorescence labeling of plant hormones is emerging as a successful strategy to track the fate of these challenging molecules inside living organisms. Thanks to the increasing availability of new fluorescent probes as well as advanced and innovative imaging technologies, we are now in a position to investigate many of the dynamic mechanisms through which plant hormones exert their action. Such a deep and detailed comprehension is mandatory for the development of new green technologies for practical applications. In this review, we summarize the results obtained so far concerning the fluorescent labeling of plant hormones, highlighting the basic steps leading to the design and synthesis of these compelling molecular tools and their applications. PMID- 27378727 TI - Significant Improvement of Cotton Verticillium Wilt Resistance by Manipulating the Expression of Gastrodia Antifungal Proteins. PMID- 27378729 TI - Comparison of Caring Ability Between Chinese and American Nursing Students. AB - This descriptive comparative study aimed to compare caring ability between Chinese and American nursing students. A survey was conducted in 544 Chinese and 109 American nursing students using Caring Ability Inventory and socio demographic data sheet. The results indicated that the Chinese nursing students reported significantly lower scores in the Caring Ability Inventory total and three subscales ( p < .001) compared with their American counterpart. Years of program and number of siblings were factors affecting the Caring Ability Inventory scores among Chinese students ( p < .05), whereas program, marital status, prior work experience, and gender were found to influence the Caring Ability Inventory scores of American students ( p < .05). Some gaps and differences between the Chinese and America nursing students' caring ability were identified. Nurse educator should leverage the influencing factors to strengthen the caring ability of nursing students in both countries. PMID- 27378728 TI - Learning from magnetotactic bacteria: A review on the synthesis of biomimetic nanoparticles mediated by magnetosome-associated proteins. AB - Much interest has gained the biomineralization process carried out by magnetotactic bacteria. These bacteria are ubiquitous in natural environments and share the ability to passively align along the magnetic field lines and actively swim along them. This ability is due to their magnetosome chain, each magnetosome consisting on a magnetic crystal enveloped by a lipid bilayer membrane to which very unique proteins are associated. Magnetotactic bacteria exquisitely control magnetosome formation, making the magnetosomes the ideal magnetic nanoparticle of potential use in many technological applications. The difficulty to scale up magnetosome production has triggered the research on the in vitro production of biomimetic (magnetosome-like) magnetite nanoparticles. In this context, magnetosome proteins are being used to mediate such in vitro magnetite precipitation experiments. The present work reviews the knowledgement on the magnetosome proteins thought to have a role on the in vivo formation of magnetite crystals in the magnetosome, and the recombinant magnetosome proteins used in vitro to form biomimetic magnetite. It also summarizes the data provided in the literature on the biomimetic magnetite nanoparticles obtained from those in vitro experiments. PMID- 27378730 TI - UBE2D2 is not involved in MuRF1-dependent muscle wasting during hindlimb suspension. AB - The Ubiquitin Proteasome System (UPS) is mainly responsible for the increased protein breakdown observed in muscle wasting. The E3 ligase MuRF1 is so far the only enzyme known to direct the main contractile proteins for degradation (i.e. troponin I, myosin heavy chains and actin). However, MuRF1 does not possess any catalytic activity and thus depends on the presence of a dedicated E2 for catalyzing the covalent binding of polyubiquitin (polyUb) chains on the substrates. The E2 enzymes belonging to the UBE2D family are commonly used for in vitro ubiquitination assays but no experimental data suggesting their physiological role as bona fide MuRF1-interacting E2 enzymes are available. In this work, we first found that the mRNA levels of critical E3 enzymes implicated in the atrophying program (MuRF1, MAFbx, Nedd4 and to a lesser extent Mdm2) are tightly and rapidly controlled during the atrophy (up regulation) and recovery (down regulation) phases in the soleus muscle from hindlimb suspended rats. By contrast, E3 ligases (Ozz, ASB2beta and E4b) implicated in other processes (muscle development or regeneration) poorly responded to atrophy and recovery. UBE2B, an E2 enzyme systematically up regulated in various catabolic situations, was controlled at the mRNA levels like the E3s implicated in the atrophying process. By contrast, UBE2D2 was progressively repressed during atrophy and recovery, which makes it a poor candidate for a role during muscle atrophy. In addition, UBE2D2 did not exhibit any affinity with MuRF1 using either yeast two hybrid or Surface Plasmon Resonance (SPR) approaches. Finally, UBE2D2 was unable to promote the degradation of the MuRF1 substrate alpha-actin in HEK293T cells, suggesting that no functional interaction exists between these enzymes within a cellular context. Altogether, our data strongly suggest that UBE2D2 is not the cognate ubiquitinating enzyme for MuRF1 and that peculiar properties of UBE2D enzymes may have biased in vitro ubiquitination assays. PMID- 27378731 TI - Inhibition of autophagy enhances effects of PF-04691502 on apoptosis and DNA damage of lung cancer cells. AB - Autophagy modulation has been considered as a potential therapeutic strategy for lung diseases. The PI3K-Akt-mTOR pathway may be one of the main targets for regulation of autophagy. We previously reported that a PI3K/mTOR dual inhibitor PF-04691502 suppressed hepatoma cells growth in vitro. However, it is still unclear whether PF-04691502 induces autophagy and its roles in DNA damage and cell death in human lung cancer cells. In this study, we investigate the effects of PF-04691502 on the autophagy and its correlation with cell apoptosis and DNA damage in non-small-cell lung cancer (NSCLC) cell lines. PF-04691502 efficiently inhibited the phosphorylation of Akt and showed dose-dependent cytotoxicity in A549 and H1299 cells. PF-04691502 also triggered apoptosis and the cleavage of caspase-3 and PARP. Phosphorylated histone H2AX (gamma-H2AX), a hallmark of DNA damage response, was dramatically induced by PF-04691502 treatment. By exposure to PF-04691502, A549 cells acquired a senescent-like phenotype with an increase in the level of beta-galactosidase. Furthermore, PF-04691502 enhanced the expression of LC3-II in a concentration-dependent manner. More interestingly, effects of PF-04691502 on toxicity and DNA damage were remarkably increased by co treatment with an autophagy inhibitor, chloroquine (CQ), in human lung cancer cells. These data suggest that a strategy of blocking autophagy to enhance the activity of PI3K/mTOR inhibitors warrants further attention in treatment of NSCLC cells. PMID- 27378732 TI - Safety and Efficacy of Mechanical Thrombectomy in Acute Ischemic Stroke of Anticoagulated Patients-A Prospective Observational Study. AB - BACKGROUND: Anticoagulated patients (APs) are excluded from the acute stroke management with alteplase in Europe, not in the United States. They could benefit from mechanical thrombectomy (MT), which was not undoubtedly proven. There are scarce data about its results in such patients. The authors' aim is to analyze the efficacy and safety of MT in APs presenting with an acute stroke in our institution. METHODS: Prospective observational study comparing 30 APs and 109 non-anticoagulated patients (N-APs) underwent direct MT without alteplase. Demographic data, clinical severity (National Institutes of Health Stroke Scale [NIHSS]), efficacy (recanalization thrombolysis in cerebral infarction [TICI] >= 2b and modified Rankin Scale score <= 2 at 3 months), and security (symptomatic intracranial hemorrhage [SICH], mortality at 3 months) were compared between both groups. RESULTS: In both groups men were more frequent (63.3% of APs were men and 61.5% of N-APs were men). Mean age was 73 in APs and 67.2 in N-APs. Median NIHSS was similar (17 APs; 16 N-APs), also TICI greater than or equal to 2b (93.3% APs; 89.9% N-APs). The 3-month modified Rankin Scale score less than or equal to 2 was 46.7% in APs and 55.2% in N-APs (P = .40). SICH was present in 16.7% of APs and 8.3% of N-APs (P = .15). Mortality at 3 months was 6.7% in APs and 19% in N-APs (P = .08). CONCLUSIONS: MT is a valid treatment option in APs. It achieves an efficacy as in N-APs with a tendency to suffer more from SICH, but lower mortality. We hypothesize that cardioembolic clots may be easier to be removed than atherotrombotics, and that embolic stroke in APs might be less severe than that in N-APs or might suffer less of other complications than atherotrombotics. PMID- 27378733 TI - A Home- and Community-Based Physical Activity Program Can Improve the Cardiorespiratory Fitness and Walking Capacity of Stroke Survivors. AB - BACKGROUND: The cardiorespiratory fitness of stroke survivors is low. Center based exercise programs that include an aerobic component have been shown to improve poststroke cardiorespiratory fitness. This pilot study aims to determine the feasibility, safety, and preliminary efficacy of an individually tailored home- and community-based exercise program to improve cardiorespiratory fitness and walking capacity in stroke survivors. METHODS: Independently ambulant, community-dwelling stroke survivors were recruited. The control (n = 10) and intervention (n = 10) groups both received usual care. In addition the intervention group undertook a 12-week, individually tailored, home- and community-based exercise program, including once-weekly telephone or e-mail support. Assessments were conducted at baseline and at 12 weeks. Feasibility was determined by retention and program participation, and safety by adverse events. Efficacy measures included change in cardiorespiratory fitness (peak oxygen consumption [VO2peak]) and distance walked during the Six-Minute Walk Test (6MWT). Analysis of covariance was used for data analysis. RESULTS: All participants completed the study with no adverse events. All intervention participants reported undertaking their prescribed program. VO2peak improved more in the intervention group (1.17 +/- .29 L/min to 1.35 +/- .33 L/min) than the control group (1.24 +/- .23 L/min to 1.24 +/- .33 L/min, between-group difference = .18 L/min, 95% confidence interval [CI]: .01-.36). Distance walked improved more in the intervention group (427 +/- 123 m to 494 +/- 67m) compared to the control group (456 +/- 101m to 470 +/- 106m, between-group difference = 45 m, 95% CI: .3-90). CONCLUSIONS: Our individually tailored approach with once-weekly telephone or e-mail support was feasible and effective in selected stroke survivors. The 16% greater improvement in VO2peak during the 6MWT achieved in the intervention versus control group is comparable to improvements attained in supervised, center-based programs. PMID- 27378734 TI - Pre-irradiation tumour volumes defined by MRI and dual time-point FET-PET for the prediction of glioblastoma multiforme recurrence: A prospective study. AB - BACKGROUND AND PURPOSE: The diagnostic accuracy of magnetic resonance imaging (MRI) for glioblastoma multiforme (GBM) is suboptimal. We analysed pre-treatment MRI- and dual time-point 18F-fluoroethylthyrosine-PET (FET-PET)-based target volumes and GBM recurrence patterns following radiotherapy with temozolomide. MATERIALS AND METHODS: Thirty-four patients with primary GBM were treated according to MRI-based treatment volumes (GTVRM). Patients underwent dual time point FET-PET scans prior to treatment, and biological tumour volumes (GTVPET) were contoured but not used for target definition. Progressions were classified based on location of primary GTVs. Volume and uniformity of MRI- vs. FET-PET/CT derived GTVs and progression patterns assessed by MRI were analysed. RESULTS: FET based GTVs measured 10min after radionuclide injection (a.r.i.; median 37.3cm(3)) were larger than GTVs measured 60min a.r.i. (median 27.7cm(3)). GTVPET volumes were significantly larger than corresponding MRI-based GTVs. MRI and PET concordance for the identification of glioblastoma GTVs was poor (mean uniformity index 0.4). 74% of failures were inside primary GTVPET volumes, with no solitary progressions inside the MRI-defined margin +20mm but outside the GTVPET detected. CONCLUSIONS: The size and geometry of GTVs differed in the majority of patients. The GTVPET volume depends on time after radionuclide injection. FET-PET better defined failure site than MRI alone. PMID- 27378735 TI - Neonatal outcomes and length of stay: A firm grasp of the obvious? PMID- 27378736 TI - Impending cardiac herniation following robotic mitral valve repair: A case report and review of the literature. PMID- 27378737 TI - Scimitar syndrome with atrial fibrillation: Repair in an adult. PMID- 27378738 TI - Tuning the magnetic properties of multisegmented Ni/Cu electrodeposited nanowires with controllable Ni lengths. AB - The fabrication of segmented Ni/Cu nanowires (NWs), with tunable structural and magnetic properties, is reported. A potentiostatic electrodeposition method with a single electrolytic bath has been used to fabricate multisegmented Ni/Cu NWs inside a highly hexagonally ordered anodic nanoporous alumina membrane, with diameters of 50 nm and Ni segment lengths (L Ni) tuned from 10 nm up to 140 nm. The x-ray diffraction results evidenced a strong dependence of the Ni NWs crystallographic face-centered-cubic (fcc) texture along the [220] direction on the aspect ratio of the NWs. The magnetic behavior of the multisegmented Ni/Cu NW arrays, as a function of the magnetic field and temperature, is also studied and correlated with their structural and morphological properties. Micromagnetic simulations, together with the experimental results, showed a dominant antiferromagnetic coupling between Ni segments along the wire length for small low aspect-ratio magnetic segments. When increasing the Ni segments' length, the magnetic interactions between these along the wire became stronger, favouring a ferromagnetic coupling. The Curie temperature of the NWs was also found to strongly depend on the Ni magnetic segment length. Particularly the Curie temperature was found to be reduced 75 K for the 20 nm Ni segments, following the finite-size scaling relation with xi 0 = 8.1 A and gamma = 0.48. These results emphasize the advantages of using a template assisted method to electrodeposit multilayer NWs, as it allows an easy tailor of the respective morphological, chemical, structural and magnetic properties. PMID- 27378739 TI - The relationships between rumination and core executive functions: A meta analysis. AB - BACKGROUND: Rumination has been thought to relate to deficits in core executive functions (EFs), but the empirical findings for this idea are mixed. The aim of the present study is to synthesize existing literature to clarify these relations. METHODS: A comprehensive literature search revealed 34 published as well as unpublished studies on the associations between rumination and core EF. These studies report on 3,066 participants. The effect size in the meta-analyses was obtained by the z transformation of correlation coefficients. RESULTS: Analysis revealed significant negative associations between rumination and both inhibition (r = -.23) and set-shifting (r = -.19). There was no significant association between rumination and working memory. These associations were not moderated by age, sex, type of sample (depressed or healthy), type of outcome measure (accuracy vs. reaction time), or affective content of the task, although statistical power for these tests was limited. CONCLUSIONS: We found significant negative associations between rumination and inhibition or set-shifting. There was no significant association between rumination and working memory. Future research should adopt multiple measures of EF to provide clear evidence on the associations between EF and rumination. A better understanding of this relationship may have important implications for intervention of rumination, such as training programs to improve EF or teach compensatory strategies to mitigate the effects of EF impairments. PMID- 27378740 TI - Head and neck cancer surgery provision in England: A current analysis of contributing specialties caseloads. AB - To ascertain the current provision for surgery for head and neck cancer in England with respect to the operative caseloads of oral and maxillofacial, ear nose and throat (ENT) and plastic surgeons, we analysed data from the 2013 report of the National Head and Neck Audit (DAHNO). Clinicians were grouped by specialty of affiliation and assigned surgical caseloads were compared. There was a wide disparity in the extent of surgical activity between the specialties (p<0.001), and the percentage of those active in head and neck oncology within each specialty similarly varied (p<0.001). PMID- 27378741 TI - Cost of training in oral and maxillofacial surgery: beyond the second degree. AB - Training in oral and maxillofacial surgery (OMFS) involves considerable personal expense, a long period of training and the need for two degrees. Other costs have also increased, with little change in pay and poor access to funding. After a Freedom of Information request and having reviewed available data, we have established the cost of training in OMFS. There is considerable regional variation in access to funding, with escalating fees for conferences and courses. Recent changes have failed to address these. PMID- 27378742 TI - Immunogenicity of the recombinant HxuCBA proteins encoded by hxuCBA gene cluster of Haemophilus parasuis in mice. AB - Haemophilus parasuis causes serious economic losses in pigs, which is the etiology of Glasser's disease. In this study we studied the immunogenicity of proteins encoded by the hxuCBA gene cluster in H. parasuis. Through bioinformatics analysis, HxuC, HxuB, and HxuA proteins were found that they might have strong antigenicity, with 31 putative cytotoxic T-lymphocyte (CTL) epitopes and multiple B-cell antigenic determinants. Western blotting assay indicated that all these antigens are highly immunogenic. The antibody levels and the levels of IL-2, IL-4, IFN-gamma in the groups of HxuA, HxuB, HxuC, HxuCBA (include HxuC, HxuB and HxuA proteins), and M-3 were observed to significantly increase with time post vaccination. HxuC, HxuB, HxuCBA and H. parasuis M-3 vaccinated groups showed a strong immune response and protection against challenge with 6.5*10(9)cfu (5*LD50) of H. parasuis M-3 strain in a mouse model, but HxuA group showed only a low level protection. Additionally, the immune response induced by all of the proteins reduced histopathological lesions and their antisera could inhibit the growth of H. parasuis. We concluded that HxuC, HxuB and HxuCBA may have potential for use as a recombinant subunit vaccine against H. parasuis challenge. PMID- 27378744 TI - Differential expression of miR-672-5p and miR-146a-5p in osteoblasts in rats after steroid intervention. AB - BACKGROUND: Apoptosis of osteoblasts and osteocytes is one cause of steroid induced osteonecrosis of the femoral head; however, the molecular mechanism of steroid affecting osteoblasts at the genetic level is unclear. The aim of the present work is to examine differential expression of osteoblasts in rats after steroid intervention and to verify expression by real-time polymerase chain reaction (RT-PCR). METHODS: Primary culture, passaging and identification of osteoblasts of SD neonatal rats were conducted; osteoblasts were divided into two groups, the control group, and the steroid group. Total RNA was extracted separately, and quality control was performed; by means of RNA labeling and microarray hybridization, data were collected and then standardized to ascertain differences in miRNA expression between the two groups. The gene expression spectrum was analyzed. Obvious differential expression of miR-672-5p and miR-146a 5p was verified by RT-PCR. Miranda, microcosm and mirdb bioinformatics software were used to predict target genes. RESULTS: Compared with the control group, morphologically, the osteoblasts in the steroid group were more irregular and showed various shapes. The number of miRNAs (fold change >2) in the steroid group was six. Four miRNAs were upregulated and two miRNAs were downregulated. In particular, upregulated miR-672-5p expression and downregulated miR-146a-5p expression were significant. RT-PCR results showed that the 2(-??) CT value of miR-672-5p in the steroid group was 3.743-fold of that in the control group, and the 2(-??) CT value of miR-146a-5p in the steroid group was 0.322-fold of that in the control group. Angptl4, Ccdc51, Ssbp3 and RGD1306991 were predicted as the target gene of miR-672-5p, while Hrp12 was that of miR-146a-5p. CONCLUSION: Expression profiles of miR-672-5p and miR-146a-5p had the most significant changes in the osteoblasts of rats with steroid intervention, which may provide a new viewpoint to pathogenesis of osteonecrosis of the femoral head. PMID- 27378743 TI - The synovial microenvironment of osteoarthritic joints alters RNA-seq expression profiles of human primary articular chondrocytes. AB - Osteoarthritis (OA) is a disabling degenerative joint disease that prompts pain and has limited treatment options. To permit early diagnosis and treatment of OA, a high resolution mechanistic understanding of human chondrocytes in normal and diseased states is necessary. In this study, we assessed the biological effects of OA-related changes in the synovial microenvironment on chondrocytes embedded within anatomically intact cartilage from joints with different pathological grades by next generation RNA-sequencing (RNA-seq). We determined the transcriptome of primary articular chondrocytes derived from anatomically unaffected knees and ankles, as well as from joints affected by OA. The GALAXY bioinformatics platform was used to facilitate biological interpretations. Comparisons of patient samples by k-means, hierarchical clustering and principal component analyses together reveal that primary chondrocytes exhibit OA grade related differences in gene expression, including genes involved in cell adhesion, ECM production and immune response. We conclude that diseased synovial microenvironments in joints with different histopathological OA grades directly alter gene expression in chondrocytes. One ramification of this finding is that anatomically intact cartilage from OA joints is not an ideal source of healthy chondrocytes, nor should these specimens be used to generate a normal baseline for the molecular characterization of diseased joints. PMID- 27378745 TI - MTHFR (C677T) CT genotype and CT-apoE3/3 genotypic combination predisposes the risk of ischemic stroke. AB - The predisposition to ischemic stroke (IS) might involve interactions of several genes and environmental factors. The present study was aimed to evaluate the influence of polymorphisms in methylenetetrahydrofolate reductase (MTHFR-C677T) and apolipoprotein-E (apo-E) as risk factors for IS patients in south Indian population. 200 IS patients and 193 age and sex matched controls were genotyped for MTHFR-C677T and apoE by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Statistically significant association was observed for MTHFR CT genotype (IS-Pooled: OR=4.29; p=5.01*10(-5); IS-Males: OR=4.13; p=0.001; IS-Females: OR=8.62; p=0.027; IS-Large Vessel Disease (LVD)- Pooled: OR=4.14; p=0.0002) and T allele (IS-Pooled: OR=4.82; p=1.49*10(-5); IS Males: OR=4.33; p=0.0002; IS-Females: OR=7.99; p=0.031; IS-LVD-Pooled: OR=4.13; p=0.0001). Further, reduced frequencies of CC genotype (IS-Pooled: OR=0.20; p=9.80*10(-6); IS-Males: OR=0.25; p=0.001; IS-Females: OR=0.12; p=0.027; IS-LVD Pooled: OR=0.23; p=0.0001) and C allele (IS-Pooled: OR=0.21; p=1.49*10(-5); IS Males: OR=0.23; p=0.0002; IS-Females: OR=0.13; p=0.031; IS-LVD-Pooled: OR=0.24; p=0.0001) were observed in IS patients than the controls. No association was observed for apoE genotypes/alleles in IS/LVD cases. Our study demonstrated the presence of risk for MTHFR CT genotype/T allele and 'CT-3/3' (n=33 vs. 5; OR=7.42; p=0.001) genotypic combination in the development of IS in south India. Further, follow-up study of these stroke cases i.e., in later stages of the disease whether they are developing the neurological disorders such as Alzheimer's Disease (AD) and vascular dementia (VaD) is needed to draw a fruitful conclusion in connection between neurological disorders and with these two polymorphisms, before translating it into clinical practice. PMID- 27378746 TI - Genetic demographic networks: Mathematical model and applications. AB - Recent improvement in the quality of genetic data obtained from extinct human populations and their ancestors encourages searching for answers to basic questions regarding human population history. The most common and successful are model-based approaches, in which genetic data are compared to the data obtained from the assumed demography model. Using such approach, it is possible to either validate or adjust assumed demography. Model fit to data can be obtained based on reverse-time coalescent simulations or forward-time simulations. In this paper we introduce a computational method based on mathematical equation that allows obtaining joint distributions of pairs of individuals under a specified demography model, each of them characterized by a genetic variant at a chosen locus. The two individuals are randomly sampled from either the same or two different populations. The model assumes three types of demographic events (split, merge and migration). Populations evolve according to the time-continuous Moran model with drift and Markov-process mutation. This latter process is described by the Lyapunov-type equation introduced by O'Brien and generalized in our previous works. Application of this equation constitutes an original contribution. In the result section of the paper we present sample applications of our model to both simulated and literature-based demographies. Among other we include a study of the Slavs-Balts-Finns genetic relationship, in which we model split and migrations between the Balts and Slavs. We also include another example that involves the migration rates between farmers and hunters-gatherers, based on modern and ancient DNA samples. This latter process was previously studied using coalescent simulations. Our results are in general agreement with the previous method, which provides validation of our approach. Although our model is not an alternative to simulation methods in the practical sense, it provides an algorithm to compute pairwise distributions of alleles, in the case of haploid non-recombining loci such as mitochondrial and Y-chromosome loci in humans. PMID- 27378747 TI - The non-equilibrium allele frequency spectrum in a Poisson random field framework. AB - In population genetic studies, the allele frequency spectrum (AFS) efficiently summarizes genome-wide polymorphism data and shapes a variety of allele frequency based summary statistics. While existing theory typically features equilibrium conditions, emerging methodology requires an analytical understanding of the build-up of the allele frequencies over time. In this work, we use the framework of Poisson random fields to derive new representations of the non-equilibrium AFS for the case of a Wright-Fisher population model with selection. In our approach, the AFS is a scaling-limit of the expectation of a Poisson stochastic integral and the representation of the non-equilibrium AFS arises in terms of a fixation time probability distribution. The known duality between the Wright-Fisher diffusion process and a birth and death process generalizing Kingman's coalescent yields an additional representation. The results carry over to the setting of a random sample drawn from the population and provide the non-equilibrium behavior of sample statistics. Our findings are consistent with and extend a previous approach where the non-equilibrium AFS solves a partial differential forward equation with a non-traditional boundary condition. Moreover, we provide a bridge to previous coalescent-based work, and hence tie several frameworks together. Since frequency-based summary statistics are widely used in population genetics, for example, to identify candidate loci of adaptive evolution, to infer the demographic history of a population, or to improve our understanding of the underlying mechanics of speciation events, the presented results are potentially useful for a broad range of topics. PMID- 27378748 TI - Family caregivers as partners in care transitions: The caregiver advise record and enable act. AB - The objective of this Perspective was to provide guidance to hospitalists and hospital clinical leadership on how to implement the Caregiver Advise Record and Enable (CARE) Act, which has been passed into law in 30 US states and territories. Specifically, the objective is 3-fold: (1) increase awareness among hospitalists and encourage them to begin to prepare for implementation, (2) explore the impetus for this legislation, and (3) provide a list of suggested resources geared to both family caregivers and healthcare professionals that may be helpful in preparation for implementing the CARE Act. Journal of Hospital Medicine 2015;11:883-885. (c) 2015 Society of Hospital Medicine. PMID- 27378749 TI - Does environmental friendliness equal healthiness? Swiss consumers' perception of protein products. AB - Food production and consumption have major impacts on the environment. At the same time, changes in human diets worldwide are increasingly leading to health problems. Both issues are highly influenced by consumers' everyday food choices and could be addressed by reducing consumption of meat and other animal products. To promote sustainable food consumption, we need to know how consumers perceive the environmental friendliness and healthiness of food products, on which criteria they base their evaluations of environmental friendliness and healthiness, and how their estimations relate to life cycle assessments and nutrient profiling. We presented 30 protein products, which varied in provenance, production methods, and processing, to 85 participants from Switzerland. They were asked to sort the products once according to their perceived environmental friendliness and once according to their perceived healthiness. The mean distances between the products were compared to the products' life cycle assessments and nutrient profiles. The results showed that perceived environmental friendliness and healthiness are highly correlated. The main predictors of the products' perceived environmental friendliness were product category, presence of an organic label, and provenance; and for perceived healthiness, these predictors were product category, fat content, processing, and presence of an organic label. Environmental friendliness and healthiness estimations were significantly correlated to the life cycle assessments and the nutrient profiles of the products, respectively. Hence, to promote healthy and environmentally friendly food choices, motivators related to environmental friendliness and healthiness could be used in synergy. Awareness about meat's environmental impact should be increased and better information is needed for consumers to make an accurate environmental impact and healthiness assessments of protein products. PMID- 27378750 TI - Motives of consumers following a vegan diet and their attitudes towards animal agriculture. AB - The number of consumers following a vegan diet has notably increased in many industrialised countries and it is likely that their influence on the food sector will continue to grow. The aim of the present study was to identify different segments of consumers according to their motivation for following a vegan diet. Another objective was to analyse the attitudes of these consumers towards animal agriculture. The main focus was to determine whether all consumers following a vegan diet oppose animal agriculture in general or if some of these consumers accept certain forms of animal agriculture. The 2014 study, conducted at seven vegan supermarkets in Germany, was based on face-to-face interviews with 329 consumers following a vegan diet. The open question on consumer motivations for adopting a vegan diet revealed three main motives: Animal-related motives (mentioned by 89.7% of the respondents), motives related to personal well-being and/or health (69.3%), and environment-related motives (46.8%). The two-step cluster analysis identified five consumer segments with different motivations for following a vegan diet. The vast majority of respondents (81.8%) mentioned more than one motive. We conclude that making a dichotomous segmentation into ethical versus self-oriented consumers, as previous authors have done, disregards the fact that many consumers following a vegan diet are driven by more than one motive. The consumer segments had significantly different attitudes towards animal agriculture. We identified consumers following a vegan diet (about one third of the sample) who might be open to forms of animal agriculture guaranteeing animal welfare standards going beyond current practices. The present study has interesting implications for the food sector and the agricultural sector. PMID- 27378751 TI - Sodium fluoride induces hypertension and cardiac complications through generation of reactive oxygen species and activation of nuclear factor kappa beta. AB - Human exposure to sodium fluoride through its daily usage is almost inevitable. Cardiovascular and renal dysfunction has been associated with fluoride toxicity. Therefore, this study investigated the mechanism of action of sodium fluoride (NaF) induced hypertension and cardiovascular complications Forty male albino rats of an average of 10 rats per group were used. Group A received clean tap water. Toxicity was induced in Group B to D by administering graded doses of NaF through drinking water ad libitum for 10 days at 150 ppm, 300 ppm, and 600 ppm concentration respectively. Following administration of NaF, there was significant increase in systolic pressure, diastolic pressure and mean arterial pressure. Markers of oxidative stress; malondialdehyde, hydrogen peroxide, advance oxidation protein products, and protein carbonyl were significantly increased in dose-dependent pattern in the cardiac and renal tissues of rats together with significant decrease in the GST activity in NaF-treated rats compared to the control. Also serum markers of inflammation, cardiac, and renal damage including myeloperoxidase, xanthine oxidase, blood urea nitrogen, creatinine, Lactate dehydrogenase (LDH), and Creatinine kinase myocardial band (CK-MB) significantly increased indicating induction of oxidative stress, renal, and cardiac damage after exposure. Histopathology of the kidney and heart revealed aberrations in the histological architecture in NaF-treated rats. Also, immunohistochemistry showed higher expression of nuclear factor kappa beta (NF kB) in the cardiac and renal tissues of rats administered NaF. Combining all, these results indicate NaF-induced hypertension through generation of reactive oxygen species and activation of renal and cardiac NF-kB expressions. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1089-1101, 2017. PMID- 27378752 TI - FOXP3(+) CD4 T-cell maturity and responses to microbial stimulation alter with age and associate with early-life gut colonization. PMID- 27378754 TI - Chapter One - Ubiquitination and Deubiquitination of G Protein-Coupled Receptors. AB - The seven-transmembrane containing G protein-coupled receptors (GPCRs) constitute the largest family of cell-surface receptors. Transmembrane signaling by GPCRs is fundamental to many aspects of physiology including vision, olfaction, cardiovascular, and reproductive functions as well as pain, behavior and psychomotor responses. The duration and magnitude of signal transduction is tightly controlled by a series of coordinated trafficking events that regulate the cell-surface expression of GPCRs at the plasma membrane. Moreover, the intracellular trafficking profiles of GPCRs can correlate with the signaling efficacy and efficiency triggered by the extracellular stimuli that activate GPCRs. Of the various molecular mechanisms that impart selectivity, sensitivity and strength of transmembrane signaling, ubiquitination of the receptor protein plays an important role because it defines both trafficking and signaling properties of the activated GPCR. Ubiquitination of proteins was originally discovered in the context of lysosome-independent degradation of cytosolic proteins by the 26S proteasome; however a large body of work suggests that ubiquitination also orchestrates the downregulation of membrane proteins in the lysosomes. In the case of GPCRs, such ubiquitin-mediated lysosomal degradation engenders long-term desensitization of transmembrane signaling. To date about 40 GPCRs are known to be ubiquitinated. For many GPCRs, ubiquitination plays a major role in postendocytic trafficking and sorting to the lysosomes. This chapter will focus on the patterns and functional roles of GPCR ubiquitination, and will describe various molecular mechanisms involved in GPCR ubiquitination. PMID- 27378753 TI - Trends, characteristics, and incidence of anaphylaxis in 2001-2010: A population based study. AB - BACKGROUND: Anaphylaxis is a potentially life-threatening systemic allergic reaction. OBJECTIVE: We aimed to determine the incidence rate and causes of anaphylaxis during a 10-year period in Olmsted County, Minnesota. METHODS: Using the resources of the Rochester Epidemiology Project, a comprehensive records linkage system, we performed a population-based incidence study in Olmsted County, Minnesota, from 2001 through 2010. All cases with a diagnosis of anaphylactic shock and 20% of cases with related diagnoses were manually reviewed. The relationships of age group, sex, and year of anaphylaxis with incidence rates were assessed by fitting Poisson regression models. RESULTS: Six hundred thirty-one cases of anaphylaxis were identified. The median age was 31 years (interquartile range, 19-44 years). The overall age- and sex-adjusted incidence rate was 42 (95% CI, 38.7-45.3) per 100,000 person-years. There was a significant increase in the overall incidence of anaphylaxis during the study period, with an average increase of 4.3% per year (P < .001). In addition, there was a 9.8% increase per year in the incidence rate of food-related anaphylaxis. Food-related anaphylaxis was most common in children aged 0 to 9 years, venom related anaphylaxis was most common in those 20 to 39 years of age, and medication-related anaphylaxis was most common in those 30 to 39 years of age. CONCLUSION: The overall incidence rate of anaphylaxis was 42 per 100,000 person years from 2001-2010 in Olmsted County, Minnesota. The incidence of anaphylaxis increased over time, and several inciting triggers were uniquely associated with different age groups. PMID- 27378755 TI - Chapter Two - Heterotrimeric G Protein Ubiquitination as a Regulator of G Protein Signaling. AB - Ubiquitin-mediated regulation of G proteins has been known for over 20 years as a result of discoveries made independently in yeast and vertebrate model systems for pheromone and photoreception, respectively. Since that time, several details underlying the cause and effect of G protein ubiquitination have been determined including the initiating signals, responsible enzymes, trafficking pathways, and their effects on protein structure, function, interactions, and cell signaling. The collective body of evidence suggests that Galpha subunits are the primary targets of ubiquitination. However, longstanding and recent results suggest that Gbeta and Ggamma subunits are also ubiquitinated, in some cases impacting cell polarization-a process essential for chemotaxis and polarized cell growth. More recently, evidence from mass spectrometry (MS)-based proteomics coupled with advances in PTM bioinformatics have revealed that protein families representing G protein subunits contain several structural hotspots for ubiquitination-most of which have not been investigated for a functional role in signal transduction. Taken together, our knowledge and understanding of heterotrimeric G protein ubiquitination as a regulator of G protein signaling-despite 20 years of research is still emerging. PMID- 27378756 TI - Chapter Three - Ubiquitination and Protein Turnover of G-Protein-Coupled Receptor Kinases in GPCR Signaling and Cellular Regulation. AB - G-protein-coupled receptors (GPCRs) are responsible for regulating a wide variety of physiological processes, and distinct mechanisms for GPCR inactivation exist to guarantee correct receptor functionality. One of the widely used mechanisms is receptor phosphorylation by specific G-protein-coupled receptor kinases (GRKs), leading to uncoupling from G proteins (desensitization) and receptor internalization. GRKs and beta-arrestins also participate in the assembly of receptor-associated multimolecular complexes, thus initiating alternative G protein-independent signaling events. In addition, the abundant GRK2 kinase has diverse "effector" functions in cellular migration, proliferation, and metabolism homeostasis by means of the phosphorylation or interaction with non-GPCR partners. Altered expression of GRKs (particularly of GRK2 and GRK5) occurs during pathological conditions characterized by impaired GPCR signaling including inflammatory syndromes, cardiovascular disease, and tumor contexts. It is increasingly appreciated that different pathways governing GRK protein stability play a role in the modulation of kinase levels in normal and pathological conditions. Thus, enhanced GRK2 degradation by the proteasome pathway occurs upon GPCR stimulation, what allows cellular adaptation to chronic stimulation in a physiological setting. beta-arrestins participate in this process by facilitating GRK2 phosphorylation by different kinases and by recruiting diverse E3 ubiquitin ligase to the receptor complex. Different proteolytic systems (ubiquitin proteasome, calpains), chaperone activities and signaling pathways influence the stability of GRKs in different ways, thus endowing specificity to GPCR regulation as protein turnover of GRKs can be differentially affected. Therefore, modulation of protein stability of GRKs emerges as a versatile mechanism for feedback regulation of GPCR signaling and basic cellular processes. PMID- 27378757 TI - Chapter 4 - Inositol 1,4,5-Trisphosphate Receptor Ubiquitination. AB - Inositol 1,4,5-trisphosphate receptors (IP3Rs) are large (~300kDa) proteins that associate into tetrameric ion channels in the endoplasmic reticulum (ER) membrane. Activation and opening of the channel upon binding of IP3 and Ca(2+) allows the flow of Ca(2+) ions from stores within the ER lumen to the cytosol, thereby promoting a number of Ca(2+)-dependent cellular events, such as secretion, neurotransmitter release, and cell division. Intriguingly, it appears that the same conformational change that IP3Rs undergo during activation makes them a target for degradation by the ubiquitin-proteasome pathway and that this mode of processing allows the cell to tune its internal Ca(2+) response to extracellular signals. Here, we review recent studies showing that activated IP3Rs interact with an array of proteins that mediate their degradation, that IP3Rs are modified by a complex array of ubiquitin conjugates, that this ubiquitination and degradation functions to regulate IP3-mediated Ca(2+) responses in the cell, and that mutations to different proteins involved in IP3R degradation result in a set of similar diseases. PMID- 27378758 TI - Chapter Five - Ubiquitination of Ion Channels and Transporters. AB - Ion channels and transporters play essential roles in excitable cells including cardiac, skeletal, and smooth muscle cells, neurons, and endocrine cells. Their dysfunction underlies the pathology of various diseases. Thus, the tight regulation of these transmembrane proteins is essential for cell physiology. While the ubiquitin system is involved in many aspects of cellular processes, this chapter focuses on the ubiquitin-mediated degradation of ion channels and transporters. Ubiquitination of ion channels and transporters is multifaceted and occurs at various cellular compartments such as the plasma membrane and the endoplasmic reticulum. While various molecules are involved in the ubiquitination of ion channels and transporters, E3 ubiquitin ligases play a central role in selectively targeting substrates for ubiquitination and will be a major focus in this chapter. To date, the Nedd4 family of E3 ubiquitin ligases and their regulations of ion channels and transporters have been extensively studied. In this chapter, we will first review Nedd4/Nedd4-2 and their regulations. We will then discuss how E3 ubiquitin ligases, especially Nedd4-2, regulate various ion channels and transporters including epithelial Na(+) channels, voltage-gated Na(+) channels, KCNQ and hERG K(+) channels, Cl(-) channels such as CFTR, transporters such as Na(+)/K(+) ATPase, and gap junctions. Furthermore, diseases caused by improper ubiquitination of ion channels and transporters will be discussed to highlight the process of ubiquitination and its biological as well as clinical significance. PMID- 27378759 TI - Chapter Six - The Ubiquitin Network in the Control of EGFR Endocytosis and Signaling. AB - Epidermal growth factor receptor (EGFR)-dependent signaling is involved in many physiological processes, and its deregulation leads to cellular dysfunctions and pathologies, of which cancer tops the list. Ubiquitin is the major determinant of EGFR fate all along the endocytic pathway, directly controlling EGFR signaling output. Indeed, the EGFR-ubiquitin network is often hijacked by cancer cells in order to have a proliferative advantage. In this chapter, we will review the different steps of EGFR activation and signal propagation, starting from the plasma membrane all the way down to the endosomal station, with a particular focus on the role of the ubiquitin system in controlling the balance between signal sustaining and downmodulation. PMID- 27378760 TI - Chapter Seven - When Phosphorylation Encounters Ubiquitination: A Balanced Perspective on IGF-1R Signaling. AB - Cell-surface receptors govern the critical information passage from outside to inside the cell and hence control important cellular decisions such as survival, growth, and differentiation. These receptors, structurally grouped into different families, utilize common intracellular signaling-proteins and pathways, yet promote divergent biological consequences. In rapid processing of extracellular signals to biological outcomes, posttranslational modifications offer a repertoire of protein processing options. Protein ubiquitination was originally identified as a signal for protein degradation through the proteasome system. It is now becoming increasingly recognized that both ubiquitin and ubiquitin-like proteins, all evolved from a common ubiquitin structural superfold, are used extensively by the cell and encompass signal tags for many different cellular fates. In this chapter we examine the current understanding of the ubiquitin regulation surrounding the insulin-like growth factor and insulin signaling systems, major members of the larger family of receptor tyrosine kinases (RTKs) and key regulators of fundamental physiological and pathological states. PMID- 27378761 TI - Chapter Eight - Ubiquitin-Mediated Regulation of Cellular Responses to Vascular Endothelial Growth Factors. AB - Vascular endothelial growth factors (VEGFs) bind receptor tyrosine kinases (VEGFRs) to regulate vascular and lymphatic development and homeostasis. Such interactions are also implicated in pathological conditions ranging from cancer to heart disease. Increasingly, it is evident that ubiquitination plays a central role in regulating VEGFR function and the cellular response to VEGFs. E1, E2, and E3 ubiquitination enzymes deliver ubiquitin-specific modifications to protein substrates but there is much debate on the exact enzymes involved. The deubiquitinase (DUB) enzymes remove such modifications and are attracting increasing interest as potential therapeutic targets in a host of different disease states. Understanding how these enzyme families regulate VEGFR function in different cells and tissues is a major challenge. An understanding of the fundamental mechanisms underlying such biochemical regulation is needed for providing new therapeutics that target diseases such as cancer and heart disease. PMID- 27378762 TI - Chapter Nine - Cellular Roles of Beta-Arrestins as Substrates and Adaptors of Ubiquitination and Deubiquitination. AB - beta-Arrestin1 and beta-arrestin2 are homologous adaptor proteins that are ubiquitously expressed in mammalian cells. They belong to a four-member family of arrestins that regulate the vast family of seven-transmembrane receptors that couple to heterotrimeric G proteins (7TMRs or GPCRs), and that modulate 7TMR signal transduction. beta-Arrestins were originally identified in the context of signal inhibition via the 7TMRs because they competed with and thereby blocked G protein coupling to 7TMRs. Currently, in addition to their role as desensitizers of signaling, beta-arrestins are appreciated as multifunctional adaptors that mediate trafficking and signal transduction of not only 7TMRs, but a growing list of additional receptors, ion channels, and nonreceptor proteins. beta-Arrestins' interactions with their multifarious partners are based on their dynamic conformational states rather than particular domain-domain interactions. beta Arrestins adopt activated conformations upon 7TMR association. In addition, beta arrestins undergo various posttranslational modifications that are choreographed by activated 7TMRs, including phosphorylation, ubiquitination, acetylation, nitrosylation, and SUMOylation. Ubiquitination of beta-arrestins is critical for their high-affinity interaction with 7TMRs as well as with endocytic adaptor proteins and signaling kinases. beta-Arrestins also function as critical adaptors for ubiquitination and deubiquitination of various cellular proteins, and thereby affect the longevity of signal transducers and the intensity of signal transmission. PMID- 27378763 TI - Preface. PMID- 27378764 TI - Obama presses Congress to agree to Zika funding. PMID- 27378765 TI - Structural changes in a Schiff base molecular assembly initiated by scanning tunneling microscopy tip. AB - We report the controlled self-organization and switching of newly designed Schiff base (E)-4-((4-(phenylethynyl) benzylidene) amino) benzenethiol (EPBB) molecules on a Au (111) surface at room temperature. Scanning tunneling microscopy and spectroscopy (STM/STS) were used to image and analyze the conformational changes of the EPBB molecules. The conformational change of the molecules was induced by using the STM tip while increasing the tunneling current. The switching of a domain or island of molecules was shown to be induced by the STM tip during scanning. Unambiguous fingerprints of the switching mechanism were observed via STM/STS measurements. Surface-enhanced Raman scattering was employed, to control and identify quantitatively the switching mechanism of molecules in a monolayer. Density functional theory calculations were also performed in order to understand the microscopic details of the switching mechanism. These calculations revealed that the molecular switching behavior stemmed from the strong interaction of the EPBB molecules with the STM tip. Our approach to controlling intermolecular mechanics provides a path towards the bottom-up assembly of more sophisticated molecular machines. PMID- 27378767 TI - Fertility, pregnancy and gynecological outcomes after fetoscopic surgery for congenital diaphragmatic hernia. AB - STUDY QUESTION: What is the impact of fetoscopic surgery for isolated Congenital Diaphragmatic Hernia (CDH) on future reproductive and gynecological outcomes? SUMMARY ANSWER: We did not observe an increase of obstetric or gynecological problems after fetoscopic surgery nor was there an increased risk for subsequent infertility. WHAT IS KNOWN ALREADY: The reproductive and gynecological outcomes of patients undergoing open maternal-fetal surgery are known. The most relevant counseling items are the elevated risk for uterine dehiscence and rupture (up to 14%). STUDY DESIGN, SIZE, DURATION: Bi-centric study over a 10-year period including 371 women carrying a fetus with isolated CDH either managed expectantly (n = 167) or operated in utero (n = 204). PARTICIPANTS/MATERIALS, SETTING, METHODS: Consenting patients filled out a survey with 23 questions (2 open and 21 multiple choice). Questionnaires were custom designed to obtain information on subsequent reproductive or gynecological problems as well as psychological impact. MAIN RESULTS AND THE ROLE OF CHANCE: The response rate was 40% (147/371). More women in the FETO group attempted a subsequent pregnancy: 70% (62/89) when compared with 47% (27/58) in controls (P = 0.009). This coincided with a longer follow-up in the FETO group (76 versus 59 months; P < 0.001) and a lower survival rate in the index pregnancy (53 versus 72%; P = 0.028). There was no difference in the number of nulliparous or parous women, neither in the conception rate. In total, there were 129 subsequent pregnancies. Nobody reported secondary fertility problems. Four women in the FETO group and one in the control reported a congenital anomaly in a subsequent pregnancy. Twenty-one pregnancies were reported with at least one complication (FETO: 23% (14/60), controls 27% (7/26)). During delivery or in the post-partum period 11 patients reported at least 1 complication (FETO 17% (10/59), controls 4% (1/24)). New onset gynecological problems occurred in 14 participants (10%). None of these events were more likely in one or the other group. Psychological and emotional impacts were frequent in both the FETO (41%) and the control groups (46%) (P = 0.691). LIMITATIONS, REASONS FOR CAUTION: The response rate was 40% (147/371), less than desired. The use of unvalidated self-reported outcomes may skew exact determination of the nature and severity of medical complications. The number of observations for uncommon events was low. The mean follow-up period to detect gynecological complications may be too short. WIDER IMPLICATIONS OF THE FINDINGS: This is the first evidence that fetoscopic surgery for CDH does not compromise future reproductive potential or obstetrical outcome when compared with expectant management. A pregnancy complicated by a serious congenital birth defect, such as CDH, frequently has a measurable psychological impact. STUDY FUNDING/COMPETING INTEREST: The authors have no conflicts to declare. J.D. receives a fundamental clinical research grant of the Fonds Wetenschappelijk Onderzoek - Vlaanderen (FWO; 18.01207). A.C.E. is supported by the Erasmus+Program of the European Union (Framework agreement number 2013-0040; contract 1011990). This was presented at the 61st meeting of the Society of Gynaecologic Investigation, in Florence, March 2014 (F-111). PMID- 27378768 TI - Ninety-five orthotopic transplantations in 74 women of ovarian tissue after cytotoxic treatment in a fertility preservation network: tissue activity, pregnancy and delivery rates. AB - STUDY QUESTION: What is the success rate in terms of ovarian activity (menstrual cycles) as well as pregnancy and delivery rates 1 year after orthotopic ovarian transplantations conducted in a three-country network? SUMMARY ANSWER: In 49 women with a follow-up >1 year after transplantation, the ovaries were active in 67% of cases and the pregnancy and delivery rates were 33 and 25%, respectively. WHAT IS KNOWN ALREADY: Cryopreservation of ovarian tissue in advance of cytotoxic therapies and later transplantation of the tissue is being performed increasingly often, and the total success rates in terms of pregnancy and delivery have been described in case series. However, published case series have not allowed either a more detailed analysis of patients with premature ovarian insufficiency (POI) or calculation of success rates based on the parameter 'tissue activity'. STUDY DESIGN, SIZE, DURATION: Retrospective analysis of 95 orthotopic transplantations in 74 patients who had been treated for cancer, performed in the FertiPROTEKT network from 2008 to June 2015. Of those 95 transplantations, a first subgroup (Subgroup 1) was defined for further analysis, including 49 women with a follow up period >1 year after transplantation. Of those 49 women, a second subgroup (Subgroup 5) was further analysed, including 40 women who were transplanted for the first time and who were diagnosed with POI before transplantation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Transplantation was performed in 16 centres and data were transferred to the FertiPROTEKT registry. The transplantations were carried out after oncological treatment had been completed and after a remission period of at least 2 years. Tissue was transplanted orthotopically, either into or onto the residual ovaries or into a pelvic peritoneal pocket. The success rates were defined as tissue activity (menstrual cycles) after 1 year (primary outcome) and as pregnancies and deliveries achieved. MAIN RESULTS AND THE ROLE OF CHANCE: The average age of all transplanted 74 women was 31 +/- 5.9 years at the time of cryopreservation and 35 +/- 5.2 at the time of transplantation. Twenty-one pregnancies and 17 deliveries were recorded. In Subgroup 1, tissue was cryopreserved at the age of 30 +/- 5.6 and transplanted at 34 +/- 4.9 years. Ovaries remained active 1 year after transplantation in 67% of cases (n = 33/49), the pregnancy rate was 33% (n = 16/49) and the delivery rate was 25% (n = 12/49). In Subgroup 5, tissue was cryopreserved at the age 30 +/- 5.9 years and transplanted at 34 +/- 5.2 years. Ovaries remained active 1 year after transplantation in 63% of cases (n = 25/40), the pregnancy rate was 28% (n = 11/40) and the delivery rate was 23% (n = 9/40). The success rates were age dependant with higher success in women who cryopreserved at a younger age. In Subgroup 5, tissue was exclusively transplanted into the ovary in 10% (n = 4/40) of women and into a peritoneal pocket in 75% (n = 30/40), resulting in spontaneous conceptions in 91% of patients (n = 10/11). LIMITATIONS, REASONS FOR CAUTION: The data were drawn from a retrospective analysis. The cryopreservation and transplantation techniques used have changed during the study period. The tissue was stored in many tissue banks and many surgeons were involved, leading to heterogeneity of the procedures. However, this does reflect the realistic situation in many countries. Although patients with POI were evaluated before transplantation to allow specific analysis of the transplanted tissue itself, the possibility cannot be excluded that residual ovarian tissue was also reactivated. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest case series worldwide to date and it confirms that cryopreservation and transplantation of ovarian tissue can be a successful option for preserving fertility. Persistent tissue activity 12 months after transplantation suggests that the pregnancy and delivery rates may increase further in the future. As transplantation into the peritoneum results in a high success rate, this approach may be an alternative to transplantation into the ovary. However, in order to establish the best transplantation site, a randomized study is required. STUDY FUNDING/COMPETING INTEREST: This study was in part funded from the Deutsche Forschungsgemeinschaft (# DI 1525) and the Wilhelm Sander Foundation (2012.127.1) and did not receive any funding from a commercial company. No competing interests. TRIAL REGISTRATION NUMBER: None. PMID- 27378769 TI - Global myocardial oedema in advanced decompensated heart failure. AB - Aims: To use cardiac magnetic resonance (CMR) imaging with quantitative T2 mapping as surrogate for myocardial water content in patients with advanced decompensated heart failure (ADHF), compare these values with T2-values observed in chronic heart failure, and evaluate the change with decongestive therapy. Methods and Results: Volumetric CMR measurements and quantitative T2 mapping were performed in 18 consecutive ADHF patients with clinical signs of volume overload. Eleven patients with stable heart failure were used as controls. Vasodilator therapy and diuretics were administered to achieve a pulmonary arterial wedge pressure (PAWP) of <18 mmHg and central venous pressure (CVP) of <12 mmHg, after which CMR was repeated. ADHF patients (62 +/- 12 years; 89% male; left ventricular ejection fraction 23 +/- 8%) presented with low cardiac index (2.08 +/- 0.59 L/min/m2), high PAWP (25 +/- 7 mmHg), and high CVP (14 +/- 5 mmHg). After decongestion, the patients had a significant increase in cardiac index (+0.41 +/- 0.53 L/min/m2; P = 0.005) and decreases in both PAWP (-9 +/- 6 mmHg; P < 0.001) and CVP (-6 +/- 5 mmHg; P < 0.001). At baseline, global left ventricular T2-values were higher in ADHF patients compared with controls (59.5 +/- 4.6 vs. 54.7 +/- 2.2 ms, respectively; P = 0.001). After decongestion, T2-values fell significantly to 55.9 +/- 5.1 ms (P = 0.001), comparable with controls (P = 0.580). In contrast, psoas muscle T2-values were similar at baseline (38.6 +/- 4.4 ms) vs. after decongestion (37.8 +/- 4.8 ms; P = 0.397). Each 1 ms decrease in global left ventricular T2-value during decongestion was associated with a 1.14 +/- 0.40 mmHg decrease in PAWP (P = 0.013), after correction for age and gender. Conclusion: Patients presenting with ADHF and volume overload have increased global left ventricular-but not psoas muscle-T2-values, which decrease with successful decongestion. Relief of myocardial oedema correlates with haemodynamic unloading. PMID- 27378766 TI - Parity, breastfeeding and risk of coronary heart disease: A pan-European case cohort study. AB - OBJECTIVE: There is uncertainty about the direction and magnitude of the associations between parity, breastfeeding and the risk of coronary heart disease (CHD). We examined the separate and combined associations of parity and breastfeeding practices with the incidence of CHD later in life among women in a large, pan-European cohort study. METHODS: Data were used from European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD, a case-cohort study nested within the EPIC prospective study of 520,000 participants from 10 countries. Information on reproductive history was available for 14,917 women, including 5138 incident cases of CHD. Using Prentice-weighted Cox regression separately for each country followed by a random-effects meta-analysis, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for CHD, after adjustment for age, study centre and several socioeconomic and biological risk factors. RESULTS: Compared with nulliparous women, the adjusted HR was 1.19 (95% CI: 1.01-1.41) among parous women; HRs were higher among women with more children (e.g., adjusted HR: 1.95 (95% CI: 1.19-3.20) for women with five or more children). Compared with women who did not breastfeed, the adjusted HR was 0.71 (95% CI: 0.52-0.98) among women who breastfed. For childbearing women who never breastfed, the adjusted HR was 1.58 (95% CI: 1.09-2.30) compared with nulliparous women, whereas for childbearing women who breastfed, the adjusted HR was 1.19 (95% CI: 0.99-1.43). CONCLUSION: Having more children was associated with a higher risk of CHD later in life, whereas breastfeeding was associated with a lower CHD risk. Women who both had children and breastfed did have a non significantly higher risk of CHD. PMID- 27378770 TI - Impact of high-intensity endurance exercise on regional left and right ventricular myocardial mechanics. AB - Aims: Strenuous endurance exercise acutely increases myocardial wall stress and evokes transient functional cardiac perturbations. However, it is unclear whether exercise-induced functional cardiac disturbances are ubiquitous throughout the myocardium or are segment specific. The aim of this study was to examine the influence of high-intensity endurance exercise on global and segmental left (LV) and right (RV) ventricular tissue deformation (strain). Methods and results: Echocardiography was used to measure strain in 23 active men (age: 28 +/- 2 years; VO2 peak: 4.5 +/- 0.7 L min-1) at rest and during a standardized low intensity exercise challenge, before and after a 90-min high-intensity endurance cycling intervention. Following the cycling intervention, LV and RV global strain decreased at rest (LV: -18.4 +/- 0.4% vs. -17.7 +/- 0.4%, P < 0.05; RV: -27.6 +/- 0.7% vs. -26.4 +/- 0.6%, P < 0.05) and by a greater extent during the low intensity exercise challenge (LV: -21.3 +/- 0.4% vs. -19.2 +/- 0.5%, P < 0.01; RV: -28.4 +/- 0.8% vs. -23.5 +/- 0.9%, P < 0.01). Reductions in LV strain were unique to regions of RV attachment (e.g. LV septum: -24.4 +/- 0.5% vs. -21.4 +/- 0.6%, P < 0.01) with lateral (-18.9 +/- 0.4% vs. -18.4 +/- 0.5%) and posterior segments (-19.5 +/- 0.4% vs. -18.8 +/- 0.7%) unaffected. Similarly, augmentation of strain from rest to exercise was abolished in the RV free wall (-1.1 +/- 1.0% vs. 2.9 +/- 1.2%, P < 0.01), reduced in the septum (-4.6 +/- 0.4% vs. -2.4 +/- 0.5%, P < 0.01), and unchanged in the lateral (-1.2 +/- 0.6% vs. -0.9 +/- 0.6%) and posterior walls (-1.7 +/- 0.6% vs. -1.3 +/- 0.7%). Conclusion: Changes in ventricular strain following high-intensity exercise are more profound in the right ventricle than in the left ventricle. Reductions in LV strain were unique to the septal myocardium and may reflect ventricular interactions secondary to exercise-induced RV dysfunction. PMID- 27378771 TI - Amyloid in the heart: an under-recognized threat at the interface of cardiology, haematology, and pathology. PMID- 27378772 TI - An AT-barrier mechanically controls DNA reannealing under tension. AB - Regulation of genomic activity occurs through the manipulation of DNA by competent mechanoenzymes. Force-clamp optical tweezers that allow the structural dynamics of the DNA molecule to be measured were used here to investigate the kinetics of mechanically-driven strand reannealing. When the force on the torsionally unconstrained lambda-phage DNA is decreased stepwise from above to below the overstretching transition, reannealing occurs via discrete shortening steps separated by exponentially distributed time intervals. Kinetic analysis reveals a transition barrier 0.58 nm along the reaction coordinate and an average reannealing-step size of ~750 bp, consistent with the average bp interval separating segments of more than 10 consecutive AT bases. In an AT-rich DNA construct, in which the distance between segments of more than 10 consecutive AT is reduced to ~210 bps, the reannealing step reduces accordingly without changes in the position of the transition barrier. Thus, the transition barrier for reannealing is determined by the presence of segments of more than 10 consecutive AT bps independent of changes in sequence composition, while the length of the reannealing strand changes according to the distance between poly-AT segments at least 10 bps long. PMID- 27378773 TI - The role of repressor kinetics in relief of transcriptional interference between convergent promoters. AB - Transcriptional interference (TI), where transcription from a promoter is inhibited by the activity of other promoters in its vicinity on the same DNA, enables transcription factors to regulate a target promoter indirectly, inducing or relieving TI by controlling the interfering promoter. For convergent promoters, stochastic simulations indicate that relief of TI can be inhibited if the repressor at the interfering promoter has slow binding kinetics, making it either sensitive to frequent dislodgement by elongating RNA polymerases (RNAPs) from the target promoter, or able to be a strong roadblock to these RNAPs. In vivo measurements of relief of TI by CI or Cro repressors in the bacteriophage lambda PR-PRE system show strong relief of TI and a lack of dislodgement and roadblocking effects, indicative of rapid CI and Cro binding kinetics. However, repression of the same lambda promoter by a catalytically dead CRISPR Cas9 protein gave either compromised or no relief of TI depending on the orientation at which it binds DNA, consistent with dCas9 being a slow kinetics repressor. This analysis shows how the intrinsic properties of a repressor can be evolutionarily tuned to set the magnitude of relief of TI. PMID- 27378774 TI - Identifying gene regulatory network rewiring using latent differential graphical models. AB - Gene regulatory networks (GRNs) are highly dynamic among different tissue types. Identifying tissue-specific gene regulation is critically important to understand gene function in a particular cellular context. Graphical models have been used to estimate GRN from gene expression data to distinguish direct interactions from indirect associations. However, most existing methods estimate GRN for a specific cell/tissue type or in a tissue-naive way, or do not specifically focus on network rewiring between different tissues. Here, we describe a new method called Latent Differential Graphical Model (LDGM). The motivation of our method is to estimate the differential network between two tissue types directly without inferring the network for individual tissues, which has the advantage of utilizing much smaller sample size to achieve reliable differential network estimation. Our simulation results demonstrated that LDGM consistently outperforms other Gaussian graphical model based methods. We further evaluated LDGM by applying to the brain and blood gene expression data from the GTEx consortium. We also applied LDGM to identify network rewiring between cancer subtypes using the TCGA breast cancer samples. Our results suggest that LDGM is an effective method to infer differential network using high-throughput gene expression data to identify GRN dynamics among different cellular conditions. PMID- 27378775 TI - RecA stimulates AlkB-mediated direct repair of DNA adducts. AB - The Escherichia coli AlkB protein is a 2-oxoglutarate/Fe(II)-dependent demethylase that repairs alkylated single stranded and double stranded DNA. Immunoaffinity chromatography coupled with mass spectrometry identified RecA, a key factor in homologous recombination, as an AlkB-associated protein. The interaction between AlkB and RecA was validated by yeast two-hybrid assay; size exclusion chromatography and standard pull down experiment and was shown to be direct and mediated by the N-terminal domain of RecA. RecA binding results AlkB RecA heterodimer formation and RecA-AlkB repairs alkylated DNA with higher efficiency than AlkB alone. PMID- 27378776 TI - Mechanism of endonuclease cleavage by the HigB toxin. AB - Bacteria encode multiple type II toxin-antitoxin modules that cleave ribosome bound mRNAs in response to stress. All ribosome-dependent toxin family members structurally characterized to date adopt similar microbial RNase architectures despite possessing low sequence identities. Therefore, determining which residues are catalytically important in this specialized RNase family has been a challenge in the field. Structural studies of RelE and YoeB toxins bound to the ribosome provided significant insights but biochemical experiments with RelE were required to clearly demonstrate which residues are critical for acid-base catalysis of mRNA cleavage. Here, we solved an X-ray crystal structure of the wild-type, ribosome-dependent toxin HigB bound to the ribosome revealing potential catalytic residues proximal to the mRNA substrate. Using cell-based and biochemical assays, we further determined that HigB residues His54, Asp90, Tyr91 and His92 are critical for activity in vivo, while HigB H54A and Y91A variants have the largest effect on mRNA cleavage in vitro Comparison of X-ray crystal structures of two catalytically inactive HigB variants with 70S-HigB bound structures reveal that HigB active site residues undergo conformational rearrangements likely required for recognition of its mRNA substrate. These data support the emerging concept that ribosome-dependent toxins have diverse modes of mRNA recognition. PMID- 27378777 TI - Entropic stabilization of folded RNA in crowded solutions measured by SAXS. AB - Non-coding RNAs must fold into specific structures that are stabilized by metal ions and other co-solutes in the cell's interior. Large crowder molecules such as PEG stabilize a bacterial group I ribozyme so that the RNA folds in low Mg2+ concentrations typical of the cell's interior. To understand the thermodynamic origins of stabilization by crowder molecules, small angle X-ray scattering was used to measure the folding and helix assembly of a bacterial group I ribozyme at different temperatures and in different MgCl2 and polyethylene glycol (PEG) concentrations. The resulting phase diagrams show that perturbations to folding by each variable do not overlap. A favorable enthalpy change drives the formation of compact, native-like structures, but requires Mg2+ ions at all temperatures studied (5-55 degrees C). PEG reduces the entropic cost of helix assembly and increases correlations between RNA segments at all temperatures. The phase diagrams also revealed a semi-compact intermediate between the unfolded and folded ensemble that is locally more flexible than the unfolded state, as judged by SHAPE modification. These results suggest that environmental variables such as temperature and solute density will favor different types of RNA structures. PMID- 27378779 TI - The functional requirement of two structural domains within telomerase RNA emerged early in eukaryotes. AB - Telomerase emerged during evolution as a prominent solution to the eukaryotic linear chromosome end-replication problem. Telomerase minimally comprises the catalytic telomerase reverse transcriptase (TERT) and telomerase RNA (TR) that provides the template for telomeric DNA synthesis. While the TERT protein is well conserved across taxa, TR is highly divergent amongst distinct groups of species. Herein, we have identified the essential functional domains of TR from the basal eukaryotic species Trypanosoma brucei, revealing the ancestry of TR comprising two distinct structural core domains that can assemble in trans with TERT and reconstitute active telomerase enzyme in vitro The upstream essential domain of T. brucei TR, termed the template core, constitutes three short helices in addition to the 11-nt template. Interestingly, the trypanosome template core domain lacks the ubiquitous pseudoknot found in all known TRs, suggesting later evolution of this critical structural element. The template-distal domain is a short stem-loop, termed equivalent CR4/5 (eCR4/5). While functionally similar to vertebrate and fungal CR4/5, trypanosome eCR4/5 is structurally distinctive, lacking the essential P6.1 stem-loop. Our functional study of trypanosome TR core domains suggests that the functional requirement of two discrete structural domains is a common feature of TRs and emerged early in telomerase evolution. PMID- 27378778 TI - An increase in negative supercoiling in bacteria reveals topology-reacting gene clusters and a homeostatic response mediated by the DNA topoisomerase I gene. AB - We studied the transcriptional response to an increase in DNA supercoiling in Streptococcus pneumoniae by using seconeolitsine, a new topoisomerase I inhibitor. A homeostatic response allowing recovery of supercoiling was observed in cells treated with subinhibitory seconeolitsine concentrations. Supercoiling increases of 40.7% (6 MUM) and 72.9% (8 MUM) were lowered to 8.5% and 44.1%, respectively. Likewise, drug removal facilitated the recovery of cell viability and DNA-supercoiling. Transcription of topoisomerase I depended on the supercoiling level. Also specific binding of topoisomerase I to the gyrase A gene promoter was detected by chromatin-immunoprecipitation. The transcriptomic response to 8 MUM seconeolitsine had two stages. An early stage, associated to an increase in supercoiling, affected 10% of the genome. A late stage, manifested by supercoiling recovery, affected 2% of the genome. Nearly 25% of the early responsive genes formed 12 clusters with a coordinated transcription. Clusters were 6.7-31.4 kb in length and included 9-22 responsive genes. These clusters partially overlapped with those observed under DNA relaxation, suggesting that bacteria manage supercoiling stress using pathways with common components. This is the first report of a coordinated global transcriptomic response that is triggered by an increase in DNA supercoiling in bacteria. PMID- 27378780 TI - Absolute quantitative measurement of transcriptional kinetic parameters in vivo. AB - mRNA expression involves transcription initiation, elongation and degradation. In cells, these dynamic processes are highly regulated. However, experimental characterization of the dynamic processes in vivo is difficult due to the paucity of methods capable of direct measurements. We present a highly sensitive and versatile method enabling direct characterization of the dynamic processes. Our method is based on single-molecule fluorescence in situ hybridization (smFISH) and quantitative analyses of hybridization signals. We hybridized multiple probes labelled with spectrally distinct fluorophores to multiple sub-regions of single mRNAs, and visualized the kinetics of synthesis and degradation of the sub regions. Quantitative analyses of the data lead to absolute quantification of the lag time of mRNA induction (the time it takes for external signals to activate transcription initiation), transcription initiation rate, transcription elongation speed (i.e. mRNA chain-growth speed), the rate of premature termination of transcripts and degradation rates. Applying our method to three different biological problems, we demonstrated how our method may be applicable to reveal dynamics of mRNA expression that was difficult to study previously. We expect such absolute quantification can greatly facilitate understanding of gene expression and its regulation working at the levels of transcriptional initiation, elongation and degradation. PMID- 27378781 TI - Annexin A2 facilitates endocytic trafficking of antisense oligonucleotides. AB - Chemically modified antisense oligonucleotides (ASOs) designed to mediate site specific cleavage of RNA by RNase H1 are used as research tools and as therapeutics. ASOs modified with phosphorothioate (PS) linkages enter cells via endocytotic pathways. The mechanisms by which PS-ASOs are released from membrane enclosed endocytotic organelles to reach target RNAs remain largely unknown. We recently found that annexin A2 (ANXA2) co-localizes with PS-ASOs in late endosomes (LEs) and enhances ASO activity. Here, we show that co-localization of ANXA2 with PS-ASO is not dependent on their direct interactions or mediated by ANXA2 partner protein S100A10. Instead, ANXA2 accompanies the transport of PS ASOs to LEs, as ANXA2/PS-ASO co-localization was observed inside LEs. Although ANXA2 appears not to affect levels of PS-ASO internalization, ANXA2 reduction caused significant accumulation of ASOs in early endosomes (EEs) and reduced localization in LEs and decreased PS-ASO activity. Importantly, the kinetics of PS-ASO activity upon free uptake show that target mRNA reduction occurs at least 4 hrs after PS-ASOs exit from EEs and is coincident with release from LEs. Taken together, our results indicate that ANXA2 facilitates PS-ASO trafficking from early to late endosomes where it may also contribute to PS-ASO release. PMID- 27378782 TI - Inverted repeat Alu elements in the human lincRNA-p21 adopt a conserved secondary structure that regulates RNA function. AB - LincRNA-p21 is a long intergenic non-coding RNA (lincRNA) involved in the p53 mediated stress response. We sequenced the human lincRNA-p21 (hLincRNA-p21) and found that it has a single exon that includes inverted repeat Alu elements (IRAlus). Sense and antisense Alu elements fold independently of one another into a secondary structure that is conserved in lincRNA-p21 among primates. Moreover, the structures formed by IRAlus are involved in the localization of hLincRNA-p21 in the nucleus, where hLincRNA-p21 colocalizes with paraspeckles. Our results underscore the importance of IRAlus structures for the function of hLincRNA-p21 during the stress response. PMID- 27378783 TI - Experimental single-strain mobilomics reveals events that shape pathogen emergence. AB - Virulence genes on mobile DNAs such as genomic islands (GIs) and plasmids promote bacterial pathogen emergence. Excision is an early step in GI mobilization, producing a circular GI and a deletion site in the chromosome; circular forms are also known for some bacterial insertion sequences (ISs). The recombinant sequence at the junctions of such circles and deletions can be detected sensitively in high-throughput sequencing data, using new computational methods that enable empirical discovery of mobile DNAs. For the rich mobilome of a hospital Klebsiella pneumoniae strain, circularization junctions (CJs) were detected for six GIs and seven IS types. Our methods revealed differential biology of multiple mobile DNAs, imprecision of integrases and transposases, and differential activity among identical IS copies for IS26, ISKpn18 and ISKpn21 Using the resistance of circular dsDNA molecules to exonuclease, internally calibrated with the native plasmids, showed that not all molecules bearing GI CJs were circular. Transpositions were also detected, revealing replicon preference (ISKpn18 prefers a conjugative IncA/C2 plasmid), local action (IS26), regional preferences, selection (against capsule synthesis) and IS polarity inversion. Efficient discovery and global characterization of numerous mobile elements per experiment improves accounting for the new gene combinations that arise in emerging pathogens. PMID- 27378784 TI - Identification of consensus binding sites clarifies FMRP binding determinants. AB - Fragile X mental retardation protein (FMRP) is a multifunctional RNA-binding protein with crucial roles in neuronal development and function. Efforts aimed at elucidating how FMRP target mRNAs are selected have produced divergent sets of target mRNA and putative FMRP-bound motifs, and a clear understanding of FMRP's binding determinants has been lacking. To clarify FMRP's binding to its target mRNAs, we produced a shared dataset of FMRP consensus binding sequences (FCBS), which were reproducibly identified in two published FMRP CLIP sequencing datasets. This comparative dataset revealed that of the various sequence and structural motifs that have been proposed to specify FMRP binding, the short sequence motifs TGGA and GAC were corroborated, and a novel TAY motif was identified. In addition, the distribution of the FCBS set demonstrates that FMRP preferentially binds to the coding region of its targets but also revealed binding along 3' UTRs in a subset of target mRNAs. Beyond probing these putative motifs, the FCBS dataset of reproducibly identified FMRP binding sites is a valuable tool for investigating FMRP targets and function. PMID- 27378785 TI - The use of an artificial nucleotide for polymerase-based recognition of carcinogenic O6-alkylguanine DNA adducts. AB - Enzymatic approaches for locating alkylation adducts at single-base resolution in DNA could enable new technologies for understanding carcinogenesis and supporting personalized chemotherapy. Artificial nucleotides that specifically pair with alkylated bases offer a possible strategy for recognition and amplification of adducted DNA, and adduct-templated incorporation of an artificial nucleotide has been demonstrated for a model DNA adduct O(6)-benzylguanine by a DNA polymerase. In this study, DNA adducts of biological relevance, O(6)-methylguanine (O(6)-MeG) and O(6)-carboxymethylguanine (O(6)-CMG), were characterized to be effective templates for the incorporation of benzimidazole-derived 2'-deoxynucleoside-5'-O triphosphates ( BENZI: TP and BIM: TP) by an engineered KlenTaq DNA polymerase. The enzyme catalyzed specific incorporation of the artificial nucleotide BENZI: opposite adducts, with up to 150-fold higher catalytic efficiency for O(6)-MeG over guanine in the template. Furthermore, addition of artificial nucleotide BENZI: was required for full-length DNA synthesis during bypass of O(6)-CMG. Selective incorporation of the artificial nucleotide opposite an O(6) alkylguanine DNA adduct was verified using a novel 2',3'-dideoxy derivative of BENZI: TP. The strategy was used to recognize adducts in the presence of excess unmodified DNA. The specific processing of BENZI: TP opposite biologically relevant O(6)-alkylguanine adducts is characterized herein as a basis for potential future DNA adduct sequencing technologies. PMID- 27378786 TI - Uptake, outcomes, and costs of implementing non-invasive prenatal testing for Down's syndrome into NHS maternity care: prospective cohort study in eight diverse maternity units. AB - OBJECTIVE: To investigate the benefits and costs of implementing non-invasive prenatal testing (NIPT) for Down's syndrome into the NHS maternity care pathway. DESIGN: Prospective cohort study. SETTING: Eight maternity units across the United Kingdom between 1 November 2013 and 28 February 2015. PARTICIPANTS: All pregnant women with a current Down's syndrome risk on screening of at least 1/1000. MAIN OUTCOME MEASURES: Outcomes were uptake of NIPT, number of cases of Down's syndrome detected, invasive tests performed, and miscarriages avoided. Pregnancy outcomes and costs associated with implementation of NIPT, compared with current screening, were determined using study data on NIPT uptake and invasive testing in combination with national datasets. RESULTS: NIPT was prospectively offered to 3175 pregnant women. In 934 women with a Down's syndrome risk greater than 1/150, 695 (74.4%) chose NIPT, 166 (17.8%) chose invasive testing, and 73 (7.8%) declined further testing. Of 2241 women with risks between 1/151 and 1/1000, 1799 (80.3%) chose NIPT. Of 71 pregnancies with a confirmed diagnosis of Down's syndrome, 13/42 (31%) with the diagnosis after NIPT and 2/29 (7%) after direct invasive testing continued, resulting in 12 live births. In an annual screening population of 698 500, offering NIPT as a contingent test to women with a Down's syndrome screening risk of at least 1/150 would increase detection by 195 (95% uncertainty interval -34 to 480) cases with 3368 (2279 to 4027) fewer invasive tests and 17 (7 to 30) fewer procedure related miscarriages, for a non-significant difference in total costs (L-46 000, L-1 802 000 to L2 661 000). The marginal cost of NIPT testing strategies versus current screening is very sensitive to NIPT costs; at a screening threshold of 1/150, NIPT would be cheaper than current screening if it cost less than L256. Lowering the risk threshold increases the number of Down's syndrome cases detected and overall costs, while maintaining the reduction in invasive tests and procedure related miscarriages. CONCLUSIONS: Implementation of NIPT as a contingent test within a public sector Down's syndrome screening programme can improve quality of care, choices for women, and overall performance within the current budget. As some women use NIPT for information only, the Down's syndrome live birth rate may not change significantly. Future research should consider NIPT uptake and informed decision making outside of a research setting. PMID- 27378788 TI - Cloud storage for endosomes. PMID- 27378787 TI - A behavioral intervention promoting physical activity in people with subacute spinal cord injury: secondary effects on health, social participation and quality of life. AB - OBJECTIVE: To assess, for people with subacute spinal cord injury, if rehabilitation that is reinforced with the addition of a behavioral intervention to promote physical activity leads to a better health, participation and quality of life. DESIGN: Randomized controlled trial. SETTING: Rehabilitation centers. PARTICIPANTS: A total of 39 participants analyzed (45 included), with subacute spinal cord injury in inpatient rehabilitation, dependent on a manual wheelchair (33% tetraplegia, 62% motor complete, 150 +/-74 days postinjury). INTERVENTION: A behavioral intervention promoting physical activity after discharge, involving 13 individual sessions delivered by a coach trained in motivational interviewing, beginning two months before and ending six months after discharge from inpatient rehabilitation. MAIN MEASURES: Physical capacity as determined during a maximal exercise test, body mass index, blood pressure, fasting lipid profile, and social participation (IMPACT-S) and quality of life (SF-36) were determined using questionnaires. Measurements were performed two months before discharge, at discharge, and six and 12 months after discharge from inpatient rehabilitation. B represents the between-group difference. RESULTS: Twelve months after discharge, significant intervention effects were found for diastolic blood pressure (B = 11.35 mmHg, 95% CI = -19.98 to -2.71), total cholesterol (B = -0.89 mmol/L, 95% CI = -1.59 to -0.20), low-density lipoprotein cholesterol (B = -0.63 mmol/L, 95% CI = -1.25 to -0.00) and participation (B = 9.91, 95% CI = 3.34 to 16.48). CONCLUSIONS: A behavioral intervention promoting physical activity after discharge from inpatient rehabilitation improves social participation and seems to reduce risk factors for cardiovascular disease in people with subacute spinal cord injury. PMID- 27378789 TI - Do we have to operate on moderate functional mitral regurgitation during aortic valve replacement for aortic stenosis? AB - A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Do we have to operate on moderate functional mitral regurgitation (FMR) during aortic valve replacement (AVR) for aortic stenosis (AS)?' Altogether 325 papers were found using the reported search, of which 9 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The current evidence obtained from these papers revealed that the significant predictors of improvement outcome include lower preoperative mitral regurgitation and lower preoperative left ventricle fractional area change. We also know that persistent atrial fibrillation, enlarged left atrium, increased indexed left ventricular mass, pulmonary hypertension and preoperative peak aortic valve gradient <60 mmHg are predictors of deterioration. Generally, we observed a trend towards improvement or non-progression of FMR following AVR for AS. In the six papers that suggest conservative treatment of FMR, the degree of mitral regurgitation (MR) improved in 45-95%, remained unchanged in 19-38% and deteriorated in 1-14%. In the three papers favoring surgical treatment of MR, the degree of MR improved in 46-69%, stay unchanged in 34-53% and deteriorated in 10%. The current evidence suggests that moderate or less grade of FMR without predictors of deterioration should be treated conservatively and moderate-severe and severe FMR warrants additional surgical procedure. A clearly randomized study, especially in patients with moderate and moderate-severe FMR for AS, seems appropriate to further elucidate surgical strategy. PMID- 27378791 TI - Pragmatic clinical trials: Emerging challenges and new roles for statisticians. AB - Patients, clinicians, and policymakers alike need access to high-quality scientific evidence in order to make informed choices about health and healthcare, but the current national clinical trials enterprise is not yet optimally configured for the efficient creation and dissemination of such evidence. However, new technologies and methods hold significant potential for accelerating the rate at which we are able to translate raw findings gathered from both patient care and clinical research into actionable knowledge. We are now entering a period in which the quantitative sciences are emerging as the critical disciplines for advancing knowledge about health and healthcare, and statisticians will increasingly serve as critical mediators in transforming data into evidence. In this new, data-centric era, biostatisticians not only need to be expert at analyzing data but should also be involved directly in diverse efforts, including the review and analysis of research portfolios in order to optimize the relevance of research questions, the use of "quality by design" principles to improve reliability and validity of each individual trial, and the mining of aggregate knowledge derived from the clinical research enterprise as a whole. In order to meet these challenges, it is imperative that we (1) nurture and build the biostatistical workforce, (2) develop a deeper understanding of the biological and clinical context among statisticians, (3) facilitate collaboration among biostatisticians and other members of the clinical trials enterprise, (4) focus on communication skills in training and education programs, and (5) enhance the quantitative capacity of the research and clinical practice worlds. PMID- 27378790 TI - Effectiveness of prophylactic levosimendan in patients with impaired left ventricular function undergoing coronary artery bypass grafting: a randomized pilot study. AB - OBJECTIVES: Perioperative low cardiac output syndrome occurs in 3-14% of patients undergoing isolated coronary artery bypass grafting (CABG), leading to significant increase in major morbidity and mortality. Considering the unique pharmacological and pharmacokinetic properties of levosimendan, we conducted a prospective, double-blind, randomized pilot study to evaluate the effectiveness of prophylactic levosimendan in patients with impaired left ventricular function undergoing CABG. METHODS: Thirty-two patients undergoing CABG with low left ventricular ejection fraction (LVEF <= 40%) were randomized to receive either a continuous infusion of levosimendan at a dose of 0.1 MUg/kg/min for 24 h without a loading dose or a placebo. The primary outcome of the study was the change in the LVEF assessed with transthoracic echocardiography on the seventh postoperative day. Secondary outcomes included the physiological and clinical effects of levosimendan. RESULTS: All patients tolerated preoperative infusion of levosimendan well. The LVEF improved in both groups; this increase was statistically significant in the levosimendan group (from 35.8 +/- 5% preoperatively to 42.8 +/- 7.8%, P = 0.001) compared with the control group (from 37.5 +/- 3.4% preoperatively to 41.2 +/- 8.3%, P = 0.1). The cardiac index, SvO2, pulmonary capillary wedge pressure and right ventricular stroke work index showed a similar trend, which was optimized in patients treated with levosimendan. Moreover, an increase in extravascular lung water was noticed in this group during the first 24 h after surgery. CONCLUSIONS: This pilot study shows that prophylactic levosimendan infusion is safe and effective in increasing the LVEF postoperatively in patients with impaired cardiac function undergoing coronary surgery. This finding may be translated to 'optimizing' patients' status before surgery. PMID- 27378792 TI - Inhibition of DNA methylation promotes breast tumor sensitivity to netrin-1 interference. AB - In a number of human cancers, NTN1 upregulation inhibits apoptosis induced by its so-called dependence receptors DCC and UNC5H, thus promoting tumor progression. In other cancers however, the selective inhibition of this dependence receptor death pathway relies on the silencing of pro-apoptotic effector proteins. We show here that a substantial fraction of human breast tumors exhibits simultaneous DNA methylation-dependent loss of expression of NTN1 and of DAPK1, a serine threonine kinase known to transduce the netrin-1 dependence receptor pro-apoptotic pathway. The inhibition of DNA methylation by drugs such as decitabine restores the expression of both NTN1 and DAPK1 in netrin-1-low cancer cells. Furthermore, a combination of decitabine with NTN1 silencing strategies or with an anti-netrin-1 neutralizing antibody potentiates tumor cell death and efficiently blocks tumor growth in different animal models. Thus, combining DNA methylation inhibitors with netrin-1 neutralizing agents may be a valuable strategy for combating cancer. PMID- 27378794 TI - Pharmacokinetic and Pharmacodynamic Properties of a Novel Inhaled Insulin. AB - Advances in insulin treatment options over recent decades have markedly improved the management of diabetes. Despite this, glycemic control remains suboptimal in many people with diabetes. Although postprandial glucose control has been improved with the development of subcutaneously injected rapid-acting insulin analogs, currently available insulins are not able to fully mimic the physiological time-action profile of endogenously secreted insulin after a meal. The delayed onset of metabolic action and prolonged period of effect induce the risk of postprandial hyperglycemia and late postprandial hypoglycemia. A number of alternative routes of insulin administration have been investigated over time in an attempt to overcome the limitations associated with subcutaneous administration and to provide an improved time-action insulin profile more closely simulating physiological prandial insulin release. Among these, pulmonary insulin delivery has shown the most promise. Technosphere(r) Inhaled Insulin (TI) is a rapid-acting inhaled human insulin recently approved by the FDA for prandial insulin therapy. In this article we discuss the pharmacokinetic and pharmacodynamic properties of TI, and, based on key studies performed during its clinical development, the implications for improved postprandial glucose control. PMID- 27378795 TI - Intraoperative Ultrasound Guidance for the Removal of Nonmetallic Foreign Body from the Foot. AB - : Ultrasound has become an increasingly valuable diagnostic tool throughout all areas of medicine. The role of diagnostic ultrasonography has an evolving role in orthopaedic surgery and particularly in the field of foot and ankle. Whether in the clinic or hospital setting, ultrasound has proven to be pivotal in the identification and localization of foreign bodies. The inherent limitations of plain films in identifying nonmetallic penetrating foreign bodies of the foot can be overcome or enhanced with the assistance of diagnostic ultrasound. LEVELS OF EVIDENCE: Therapeutic, Level IV: Case report. PMID- 27378793 TI - Neurotrophin Genes and Antidepressant-Worsening Suicidal Ideation: A Prospective Case-Control Study. AB - BACKGROUND: Antidepressant-worsening suicidal ideation is a rare but serious phenomenon. This study aimed to test for association between antidepressant worsening suicidal ideation and polymorphisms of BDNF/NTRK2 neurotrophin pathway genes, known to be involved in depression and suicide. METHODS: This was a case control study comparing patients with antidepressant-worsening suicidal ideation to patients without. Patients were collected from the GENESE cohort (3771 depressed tianeptine-treated outpatients). Antidepressant-worsening suicidal ideation was defined by an increase of at least 2 points on the Montgomery-Asberg Depression Rating Scale-item10 during treatment. Controls were matched for age, sex, and baseline Montgomery-Asberg Depression Rating Scale-item10 score. Thirteen single nucleotide polymorphisms covering 5 BDNF/NTRK2 pathway genes were genotyped. RESULTS: A total 78 cases and 312 controls were included. Two NTRK2 single nucleotide polymorphisms were associated to antidepressant-worsening suicidal ideation: rs1439050 (P=.01) and rs1867283 (P=.04). Association with rs1439050 remained significant after adjustment for potentially confounding factors, including previous suicide attempts (P<.01). CONCLUSIONS: This naturalistic prospective study is consistent with previous studies on highlighting the potential role of the neurotrophin pathway, and especially of NTRK2, in antidepressant-worsening suicidal ideation. PMID- 27378797 TI - George C Williams Prize 2015. PMID- 27378796 TI - Cohort Profile: The Birmingham Chronic Obstructive Pulmonary Disease (COPD) Cohort Study. PMID- 27378798 TI - Depression and anxiety: maladaptive byproducts of adaptive mechanisms. PMID- 27378800 TI - Weight stigma in frequent exercisers: Overt, demeaning and condescending. AB - The aim of this study was to qualitatively examine weight stigma in individuals who exercise frequently. In total, six focus groups, comprising 30 participants aged 18-25 years, were conducted using convenience sampling. All participants were frequent exercisers. Five themes emerged in the data with participants discussing bullying, the consequences of obesity, causes of obesity, lack of willpower and interventions to reduce obesity. This study is the first qualitative examination of weight stigmatisation in frequent exercisers, where the beliefs reported by focus group participants suggest that frequent exercisers stigmatise, discriminate and dehumanise obese people. Future research to examine the impact of weight stigma on exercise motivation and behaviour of obese people appears warranted. PMID- 27378799 TI - What Does It Cost to Improve Household Diets in Nepal? Using the Cost of the Diet Method to Model Lowest Cost Dietary Changes. AB - BACKGROUND: In Nepal, limited availability and affordability of nutritious foods contribute to malnutrition. OBJECTIVES: To identify nutrient deficiencies in commonly consumed diets and model lowest cost changes that could improve diet quality in 3 agroecological zones of Nepal. METHODS: In August to September 2014, we collected market price and women's food frequency data from 3 representative villages in Nepal's mountains (Mahat Gaun, Jumla, n = 181 households), hills (Sitapur, Arghakhanchi, n = 166), and terai (Saigaun, Banke, n = 232) and verified local diets during women's group discussions. Using the Cost of the Diet method, we compared models of the most nutritious version of a commonly consumed diet given locally available foods ("common diet") with the cheapest possible diet meeting nutrient requirements, including foods not currently available ("optimal diet"). RESULTS: The household common diet lacks sufficient vitamin B12, riboflavin, and calcium in the mountains; B6, B12, calcium, and iron in the hills; vitamin A, calcium, and iron in the terai. Adding fish to the mountain and hill diets and increasing dark green leafy vegetable consumption in all zones yielded nutritional adequacy. Optimal diets are more expensive than the common diet in the mountains and hills but less expensive in the terai. CONCLUSION: The modeled lowest cost diet commonly eaten in 3 Nepalese communities lacks key nutrients. Policies and interventions that increase market availability and consumption of vitamin B12- and calcium-rich fish and dark green leafy vegetables could improve local diets, particularly in the mountains and hills. PMID- 27378801 TI - Form or function: Does focusing on body functionality protect women from body dissatisfaction when viewing media images? AB - We examined whether shifting young women's ( N =322) attention toward functionality components of media-portrayed idealized images would protect against body dissatisfaction. Image type was manipulated via images of models in either an objectified body-as-object form or active body-as-process form; viewing focus was manipulated via questions about the appearance or functionality of the models. Social comparison was examined as a moderator. Negative outcomes were most pronounced within the process-related conditions (body-as-process images or functionality viewing focus) and for women who reported greater functionality comparison. Results suggest that functionality-based depictions, reflections, and comparisons may actually produce worse outcomes than those based on appearance. PMID- 27378802 TI - Natural kinds, psychiatric classification and the history of the DSM. AB - This paper addresses philosophical issues concerning whether mental disorders are natural kinds and how the DSM should classify mental disorders. I argue that some mental disorders (e.g. schizophrenia, depression) are natural kinds in the sense that they are natural classes constituted by a set of stable biological mechanisms. I subsequently argue that a theoretical and causal approach to classification would provide a method for classifying natural kinds that is superior to the purely descriptive approach adopted by the DSM since DSM-III My argument suggests that the DSM should classify natural kinds in order to provide predictively useful (i.e. projectable) diagnostic categories and that a causal approach to classification would provide a more promising method for formulating valid diagnostic categories. PMID- 27378804 TI - Susceptibility-weighted MRI signs of compensatory mechanism in nonconvulsive status epilepticus. PMID- 27378805 TI - Cranial bone collapse in microcephalic infants prenatally exposed to Zika virus infection. PMID- 27378806 TI - Disruption of posteromedial large-scale neural communication predicts recovery from coma. PMID- 27378807 TI - Calcified otogenic brain abscess. PMID- 27378808 TI - Child Neurology: Two sisters with dystonia and regression: PLA2G6-associated neurodegeneration. PMID- 27378809 TI - Teaching NeuroImages: White matter hypomyelination and progressive calcifications in cerebral folate deficiency. PMID- 27378810 TI - Teaching NeuroImages: Hemigeographic tongue following an acute ischemic stroke. PMID- 27378811 TI - Accelerating international MS care through videoconference-based education and case consultation. PMID- 27378812 TI - Comparing human respiratory adverse effects after acute exposure to particulate matter in conventional and particle-reduced swine building environments. AB - OBJECTIVES: To evaluate innate immunity responses, lung function and symptoms in volunteers acutely exposed to organic dust in swine buildings after installing particle separators aimed to reduce particulate matter exposure. METHODS: 11 healthy participants were exposed in 2 different facilities, with and without installed particle separators, in a cross-over design including 2-3 weeks wash out between the 2 exposures. Size, distribution and composition of particulate matter and endotoxins in the air were measured. Lung function (spirometry), bronchial responsiveness, symptoms questionnaire and markers of innate immunity in blood and nasal lavage were measured before and after the 3-hour exposures. RESULTS: The number of particles, in particular fine particles sized 0.3-0.5 um, was reduced in the particle-separated swine building environment (PSE) compared with that in the conventional building (CE). In the PSE, headache (p=0.03) and increased body temperature (p=0.016) were less pronounced than in the CE. The expression of toll-like receptors (TLR)2 and TLR4 on blood monocytes significantly increased (p=0.016 and 0.017, respectively) while cluster of differentiation (CD)14 on neutrophils decreased (p=0.05) after exposure in the CE, yet with no difference between the 2 exposures. Compared with the conventional environment, exposure to the PSE yielded lower interleukin (IL)-6 (p=0.02) and IL-8 (p=0.04) levels in the upper respiratory tract, as assessed by nasal lavage. CONCLUSIONS: Particulate matter and organic dust in the swine building were reduced after installing particle separators, which, in naive never exposed volunteers, in turn reduced adverse health effects caused by acute exposure in swine buildings compared with exposure to the conventional swine building environment. PMID- 27378813 TI - ROMK expression remains unaltered in a mouse model of familial hyperkalemic hypertension caused by the CUL3Delta403-459 mutation. AB - Familial hyperkalemic hypertension (FHHt) is a rare inherited form of salt dependent hypertension caused by mutations in proteins that regulate the renal Na(+)-Cl(-) cotransporter NCC Mutations in four genes have been reported to cause FHHt including CUL3 (Cullin3) that encodes a component of a RING E3 ligase. Cullin-3 binds to WNK kinase-bound KLHL3 (the substrate recognition subunit of the ubiquitin ligase complex) to promote ubiquitination and proteasomal degradation of WNK kinases. Deletion of exon 9 from CUL3 (affecting residues 403 459, CUL3(Delta403-459)) causes a severe form of FHHt (PHA2E) that is recapitulated closely in a knock-in mouse model. The loss of functionality of CUL3(Delta403-459) and secondary accumulation of WNK kinases causes substantial NCC activation. This accounts for the hypertension in FHHt but the origin of the hyperkalemia is less clear. Hence, we explored the impact of CUL3(Delta403-459) on expression of the distal secretory K channel, ROMK, both in vitro and in vivo. We found that expressing wild-type but not the CUL3(Delta403-459) mutant form of CUL3 prevented the suppression of ROMK currents by WNK4 expressed in Xenopus oocytes. The mutant CUL3 protein was also unable to affect ROMK-EGFP protein expression at the surface of mouse M-1 cortical collecting duct (CCD) cells. The effects of CUL3 on ROMK expression in both oocytes and M-1 CCD cells was reduced by addition of the neddylation inhibitor, MLN4924. This confirms that neddylation is important for CUL3 activity. Nevertheless, in our knock-in mouse model expressing CUL3(Delta403-459) we could not show any alteration in ROMK expression by either western blotting whole kidney lysates or confocal microscopy of kidney sections. This suggests that the hyperkalemia in our knock-in mouse and human PHA2E subjects with the CUL3(Delta403-459) mutation is not caused by reduced ROMK expression in the distal nephron. PMID- 27378814 TI - Efficacy of anidulafungin in the treatment of experimental Candida parapsilosis catheter infection using an antifungal-lock technique. AB - OBJECTIVES: The effectiveness of anidulafungin versus liposomal amphotericin B (LAmB) for treating experimental Candida parapsilosis catheter-related infection by an antifungal-lock technique was assessed. METHODS: Two clinical strains of C. parapsilosis (CP12 and CP54) were studied. In vitro studies were used to determine the biofilm MICs (MBIC50 and MBIC90) by XTT reduction assay and LIVE/DEAD biofilm viability for anidulafungin and LAmB on 96-well microtitre polystyrene plates and silicone discs. An intravenous catheter was implanted in New Zealand white rabbits. Infection was induced by locking the catheter for 48 h with the inoculum. The 48 h antifungal-lock treatment groups included control, 3.3 mg/mL anidulafungin and 5.5 mg/mL LAmB. RESULTS: Anidulafungin showed better in vitro activity than LAmB against C. parapsilosis growing in biofilm on silicone discs. MBIC90 of LAmB: CP12, >1024 mg/L; CP54, >1024 mg/L. MBIC90 of anidulafungin: CP12, 1 mg/L; CP54, 1 mg/L (P <= 0.05). Moreover, only anidulafungin (1 mg/L) showed >90% non-viable cells in the LIVE/DEAD biofilm viability assay on silicone discs. No differences were observed between the in vitro susceptibility of anidulafungin or LAmB when 96-well plates were used. Anidulafungin achieved significant reductions relative to LAmB in log10 cfu recovered from the catheter tips for both strains (P <= 0.05). Only anidulafungin achieved negative catheter tip cultures (CP12 63%, CP54 73%, P <= 0.05). CONCLUSIONS: Silicone discs may be a more reliable substrate for the study of in vitro biofilm susceptibility of C. parapsilosis. Anidulafungin-lock therapy showed the highest activity for experimental catheter-related infection with C. parapsilosis. PMID- 27378815 TI - The Systemic Acquired Resistance Regulator OsNPR1 Attenuates Growth by Repressing Auxin Signaling through Promoting IAA-Amido Synthase Expression. AB - Systemic acquired resistance is a long-lasting and broad-spectrum disease resistance to pathogens. Our previous study demonstrated that overexpression of NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (OsNPR1), a master gene for systemic acquired resistance in rice (Oryza sativa), greatly enhanced resistance to bacterial blight caused by Xanthomonas oryzae pv oryzae However, the growth and development of the OsNPR1 overexpression (OsNPR1-OX) plants were restrained, and the mechanism remained elusive. In this study, we dissected the OsNPR1-induced growth inhibition. We found that the OsNPR1-OX lines displayed phenotypes mimicking auxin-defective mutants, with decreases in root system, seed number and weight, internode elongation, and tiller number. Whole-genome expression analysis revealed that genes related to the auxin metabolism and signaling pathway were differentially expressed between the OsNPR1-OX and wild-type plants. Consistently, the indole-3-acetic acid (IAA) content was decreased and the auxin distribution pattern was altered in OsNPR1-OX plants. Importantly, we found that some GH3 family members, in particular OsGH3.8 coding IAA-amido synthetase, were constitutively up-regulated in OsNPR1-OX plants. Decreased OsGH3.8 expression by RNA interference could partially restore IAA level and largely rescue the restrained growth and development phenotypes but did not affect the disease resistance of OsNPR1-OX plants. Taken together, we revealed that OsNPR1 affects rice growth and development by disrupting the auxin pathway at least partially through indirectly up-regulating OsGH3.8 expression. PMID- 27378816 TI - A Brachypodium UDP-Glycosyltransferase Confers Root Tolerance to Deoxynivalenol and Resistance to Fusarium Infection. AB - Fusarium head blight (FHB) is a cereal disease caused by Fusarium graminearum, a fungus able to produce type B trichothecenes on cereals, including deoxynivalenol (DON), which is harmful for humans and animals. Resistance to FHB is quantitative, and the mechanisms underlying resistance are poorly understood. Resistance has been related to the ability to conjugate DON into a glucosylated form, deoxynivalenol-3-O-glucose (D3G), by secondary metabolism UDP glucosyltransferases (UGTs). However, functional analyses have never been performed within a single host species. Here, using the model cereal species Brachypodium distachyon, we show that the Bradi5g03300 UGT converts DON into D3G in planta. We present evidence that a mutation in Bradi5g03300 increases root sensitivity to DON and the susceptibility of spikes to F. graminearum, while overexpression confers increased root tolerance to the mycotoxin and spike resistance to the fungus. The dynamics of expression and conjugation suggest that the speed of DON conjugation rather than the increase of D3G per se is a critical factor explaining the higher resistance of the overexpressing lines. A detached glumes assay showed that overexpression but not mutation of the Bradi5g03300 gene alters primary infection by F. graminearum, highlighting the involvement of DON in early steps of infection. Together, these results indicate that early and efficient UGT-mediated conjugation of DON is necessary and sufficient to establish resistance to primary infection by F. graminearum and highlight a novel strategy to promote FHB resistance in cereals. PMID- 27378817 TI - Fatostatin Inhibits Cancer Cell Proliferation by Affecting Mitotic Microtubule Spindle Assembly and Cell Division. AB - The sterol regulatory element-binding protein (SREBP) transcription factors have become attractive targets for pharmacological inhibition in the treatment of metabolic diseases and cancer. SREBPs are critical for the production and metabolism of lipids and cholesterol, which are essential for cellular homeostasis and cell proliferation. Fatostatin was recently discovered as a specific inhibitor of SREBP cleavage-activating protein (SCAP), which is required for SREBP activation. Fatostatin possesses antitumor properties including the inhibition of cancer cell proliferation, invasion, and migration, and it arrests cancer cells in G2/M phase. Although Fatostatin has been viewed as an antitumor agent due to its inhibition of SREBP and its effect on lipid metabolism, we show that Fatostatin's anticancer properties can also be attributed to its inhibition of cell division. We analyzed the effect of SREBP activity inhibitors including Fatostatin, PF-429242, and Betulin on the cell cycle and determined that only Fatostatin possessed antimitotic properties. Fatostatin inhibited tubulin polymerization, arrested cells in mitosis, activated the spindle assembly checkpoint, and triggered mitotic catastrophe and reduced cell viability. Thus Fatostatin's ability to inhibit SREBP activity and cell division could prove beneficial in treating aggressive types of cancers such as glioblastomas that have elevated lipid metabolism and fast proliferation rates and often develop resistance to current anticancer therapies. PMID- 27378819 TI - Synthesis of beta-substituted tryptamines by regioselective ring opening of aziridines. AB - Functionalized tryptamines are targets of interest for development as small molecule therapeutics. The ring opening of aziridines with indoles is a powerful method for tryptamine synthesis if site selectivity can be controlled. 4 Nitrobenzyl carbamate (PNZ)-protected aziridines undergo regioselective ring opening to produce beta-substituted tryptamines for a series of indoles. The PNZ protected tryptamines can be further manipulated by PNZ removal under mild conditions. PMID- 27378818 TI - Single-molecule Force Spectroscopy Reveals the Calcium Dependence of the Alternative Conformations in the Native State of a betagamma-Crystallin Protein. AB - Although multidomain proteins predominate the proteome of all organisms and are expected to display complex folding behaviors and significantly greater structural dynamics as compared with single-domain proteins, their conformational heterogeneity and its impact on their interaction with ligands are poorly understood due to a lack of experimental techniques. The multidomain calcium binding betagamma-crystallin proteins are particularly important because their deterioration and misfolding/aggregation are associated with melanoma tumors and cataracts. Here we investigate the mechanical stability and conformational dynamics of a model calcium-binding betagamma-crystallin protein, Protein S, and elaborate on its interactions with calcium. We ask whether domain interactions and calcium binding affect Protein S folding and potential structural heterogeneity. Our results from single-molecule force spectroscopy show that the N-terminal (but not the C-terminal) domain is in equilibrium with an alternative conformation in the absence of Ca(2+), which is mechanically stable in contrast to other proteins that were observed to sample a molten globule under similar conditions. Mutagenesis experiments and computer simulations reveal that the alternative conformation of the N-terminal domain is caused by structural instability produced by the high charge density of a calcium binding site. We find that this alternative conformation in the N-terminal domain is diminished in the presence of calcium and can also be partially eliminated with a hitherto unrecognized compensatory mechanism that uses the interaction of the C-terminal domain to neutralize the electronegative site. We find that up to 1% of all identified multidomain calcium-binding proteins contain a similarly highly charged site and therefore may exploit a similar compensatory mechanism to prevent structural instability in the absence of ligand. PMID- 27378820 TI - Impact of increasing heat waves on U.S. ozone episodes in the 2050s: Results from a multimodel analysis using extreme value theory. AB - We develop a statistical model using extreme value theory to estimate the 2000 2050 changes in ozone episodes across the United States. We model the relationships between daily maximum temperature (Tmax) and maximum daily 8-hour average (MDA8) ozone in May-September over 2003-2012 using a Point Process (PP) model. At ~20% of the sites, a marked decrease in the ozone-temperature slope occurs at high temperatures, defined as ozone suppression. The PP model sometimes fails to capture ozone-Tmax relationships, and so we refit the ozone-Tmax slope using logistic regression and a Generalized Pareto Distribution model. We then apply the resulting hybrid-EVT model to projections of Tmax from an ensemble of downscaled climate models. Assuming constant anthropogenic emissions at the present level, we find an average increase of 2.3 days a-1 in ozone episodes (> 75 ppbv) across the United States by the 2050s, with a change of +3-9 days a-1 at many sites. PMID- 27378821 TI - Transfer Learning for Class Imbalance Problems with Inadequate Data. AB - A fundamental problem in data mining is to effectively build robust classifiers in the presence of skewed data distributions. Class imbalance classifiers are trained specifically for skewed distribution datasets. Existing methods assume an ample supply of training examples as a fundamental prerequisite for constructing an effective classifier. However, when sufficient data is not readily available, the development of a representative classification algorithm becomes even more difficult due to the unequal distribution between classes. We provide a unified framework that will potentially take advantage of auxiliary data using a transfer learning mechanism and simultaneously build a robust classifier to tackle this imbalance issue in the presence of few training samples in a particular target domain of interest. Transfer learning methods use auxiliary data to augment learning when training examples are not sufficient and in this paper we will develop a method that is optimized to simultaneously augment the training data and induce balance into skewed datasets. We propose a novel boosting based instance-transfer classifier with a label-dependent update mechanism that simultaneously compensates for class imbalance and incorporates samples from an auxiliary domain to improve classification. We provide theoretical and empirical validation of our method and apply to healthcare and text classification applications. PMID- 27378822 TI - Integrating Expert Knowledge with Data in Bayesian Networks: Preserving Data Driven Expectations when the Expert Variables Remain Unobserved. AB - When developing a causal probabilistic model, i.e. a Bayesian network (BN), it is common to incorporate expert knowledge of factors that are important for decision analysis but where historical data are unavailable or difficult to obtain. This paper focuses on the problem whereby the distribution of some continuous variable in a BN is known from data, but where we wish to explicitly model the impact of some additional expert variable (for which there is expert judgment but no data). Because the statistical outcomes are already influenced by the causes an expert might identify as variables missing from the dataset, the incentive here is to add the expert factor to the model in such a way that the distribution of the data variable is preserved when the expert factor remains unobserved. We provide a method for eliciting expert judgment that ensures the expected values of a data variable are preserved under all the known conditions. We show that it is generally neither possible, nor realistic, to preserve the variance of the data variable, but we provide a method towards determining the accuracy of expertise in terms of the extent to which the variability of the revised empirical distribution is minimised. We also describe how to incorporate the assessment of extremely rare or previously unobserved events. PMID- 27378823 TI - Soluble Urokinase-Type Plasminogen Activator Receptor Plasma Concentration May Predict Susceptibility to High Altitude Pulmonary Edema. AB - Introduction. Acute exposure to high altitude induces inflammation. However, the relationship between inflammation and high altitude related illness such as high altitude pulmonary edema (HAPE) and acute mountain sickness (AMS) is poorly understood. We tested if soluble urokinase-type plasminogen activator receptor (suPAR) plasma concentration, a prognostic factor for cardiovascular disease and marker for low grade activation of leukocytes, will predict susceptibility to HAPE and AMS. Methods. 41 healthy mountaineers were examined at sea level (SL, 446 m) and 24 h after rapid ascent to 4559 m (HA). 24/41 subjects had a history of HAPE and were thus considered HAPE-susceptible (HAPE-s). Out of the latter, 10/24 HAPE-s subjects were randomly chosen to suppress the inflammatory cascade with dexamethasone 8 mg bid 24 h prior to ascent. Results. Acute hypoxic exposure led to an acute inflammatory reaction represented by an increase in suPAR (1.9 +/ 0.4 at SL versus 2.3 +/- 0.5 at HA, p < 0.01), CRP (0.7 +/- 0.5 at SL versus 3.6 +/- 4.6 at HA, p < 0.01), and IL-6 (0.8 +/- 0.4 at SL versus 3.3 +/- 4.9 at HA, p < 0.01) in all subjects except those receiving dexamethasone. The ascent associated decrease in PaO2 correlated with the increase in IL-6 (r = 0.46, p < 0.001), but not suPAR (r = 0.27, p = 0.08); the increase in IL-6 was not correlated with suPAR (r = 0.16, p = 0.24). Baseline suPAR plasma concentration was higher in the HAPE-s group (2.0 +/- 0.4 versus 1.8 +/- 0.4, p = 0.04); no difference was found for CRP and IL-6 and for subjects developing AMS. Conclusion. High altitude exposure leads to an increase in suPAR plasma concentration, with the missing correlation between suPAR and IL-6 suggesting a cytokine independent, leukocyte mediated mechanism of low grade inflammation. The correlation between IL-6 and PaO2 suggests a direct effect of hypoxia, which is not the case for suPAR. However, suPAR plasma concentration measured before hypoxic exposure may predict HAPE susceptibility. PMID- 27378824 TI - Effect of Traditional Chinese Medicine on Inflammatory Mediators in Pediatric Asthma. AB - Objective. To observe the effects of empirical prescriptions of traditional Chinese medicine (TCM) on inflammatory mediators in pediatric asthma and to explore the underlying molecular mechanism in the treatment of asthma. Methods. A total of 182 children with asthma were randomly placed into either the TCM group (n = 97) or the salbutamol and montelukast (SM) group (n = 85). Patients in the TCM group were treated with a series of empirical prescriptions of TCM, while those in the SM group received salbutamol and montelukast. Both groups received their respective treatment for 12 weeks. There were 35 patients in TCM group and 34 patients in SM group providing venous blood. Real-time PCR was used to determine the mRNA expression levels of interleukin- (IL-) 10, IL-17, matrix metalloproteinase-9 (MMP-9), and transforming growth factor beta1 (TGF-beta1) in peripheral blood mononuclear cells before and after treatment. Enzyme-linked immunosorbent assay was used to measure the levels of IL-10, IL-17, MMP-9, and TGF-beta1 in peripheral blood before and after treatment. Results. The mRNA expression of TGF-beta1 in the SM group was downregulated (P = 0.00) after treatment. No significant differences were found between the TCM group and the SM group after treatment (P > 0.05). In the TCM group, the levels of IL-10, IL-17, and MMP-9 significantly decreased after treatment (P = 0.01, 0.04, and 0.03, resp.). In the SM group, IL-17, MMP-9, and TGF-beta1 levels significantly decreased after treatment (P = 0.00, 0.03, and 0.00, resp.). There was no significant difference between the two groups regarding the levels of IL-10, IL 17, TGF-beta1, and MMP-9 (P > 0.05). The difference of the level of IL-17 was negatively correlated with the change of C-ACT score in TCM group and SM group. Conclusion. TCM has a regulatory effect on the balance of some inflammatory mediators in pediatric asthma. PMID- 27378825 TI - Induction of Mast Cell Accumulation by Tryptase via a Protease Activated Receptor 2 and ICAM-1 Dependent Mechanism. AB - Mast cells are primary effector cells of allergy, and recruitment of mast cells in involved tissue is one of the key events in allergic inflammation. Tryptase is the most abundant secretory product of mast cells, but little is known of its influence on mast cell accumulation. Using mouse peritoneal model, cell migration assay, and flow cytometry analysis, we investigated role of tryptase in recruiting mast cells. The results showed that tryptase induced up to 6.7-fold increase in mast cell numbers in mouse peritoneum following injection. Inhibitors of tryptase, an antagonist of PAR-2 FSLLRY-NH2, and pretreatment of mice with anti-ICAM-1, anti-CD11a, and anti-CD18 antibodies dramatically diminished tryptase induced mast cell accumulation. On the other hand, PAR-2 agonist peptides SLIGRL-NH2 and tc-LIGRLO-NH2 provoked mast cell accumulation following injection. These implicate that tryptase induced mast cell accumulation is dependent on its enzymatic activity, activation of PAR-2, and interaction between ICAM-1 and LFA-1. Moreover, induction of trans-endothelium migration of mast cells in vitro indicates that tryptase acts as a chemoattractant. In conclusion, provocation of mast cell accumulation by mast cell tryptase suggests a novel self amplification mechanism of mast cell accumulation. Mast cell stabilizers as well as PAR-2 antagonist agents may be useful for treatment of allergic reactions. PMID- 27378826 TI - Small Interfering RNA Targeted to ASPP2 Promotes Progression of Experimental Proliferative Vitreoretinopathy. AB - Background. Epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) is vital in proliferative vitreoretinopathy (PVR) development. Apoptosis stimulating proteins of p53 (ASPP2) have recently been reported to participate in EMT. However, the role of ASPP2 in PVR pathogenesis has not been identified. Methods. Immunohistochemistry was used to investigate the expression of ASPP2 in epiretinal membranes of PVR patients. ARPE-19 cells were transfected with ASPP2 siRNA, followed with measurement of cell cytotoxicity, proliferation, and migration ability. EMT markers and related inflammatory and fibrosis cytokines were measured by western blot or flow cytometry. Additionally, PVR rat models were induced by intravitreal injection of ARPE-19 cells transfected with ASPP2 siRNA and evaluated accordingly. Results. Immunofluorescence analysis revealed less intense expression of ASPP2 in PVR membranes. ASPP2 knockdown facilitated the proliferation and migration of RPE cells and enhanced the expression of mesenchymal markers such as alpha smooth muscle actin, fibronectin, and ZEB1. Meanwhile, ASPP2-siRNA increased EMT-related and inflammatory cytokines, including TGF-beta, CTGF, VEGF, TNF-alpha, and interleukins. PVR severities were more pronounced in the rat models with ASPP2-siRNA treatment. Conclusions. ASPP2 knockdown promoted EMT of ARPE-19 cells in vitro and exacerbated the progression of experimental PVR in vivo, possibly via inflammatory and fibrosis cytokines. PMID- 27378827 TI - Caspase-11 Modulates Inflammation and Attenuates Toxoplasma gondii Pathogenesis. AB - Toxoplasma gondii is an obligate intracellular parasite that is the etiologic agent responsible for toxoplasmosis. Infection with T. gondii results in activation of nucleotide binding domain and leucine rich repeat containing receptors (NLRs). NLR activation leads to inflammasome formation, the activation of caspase-1, and the subsequent cleavage of IL-1beta and IL-18. Recently, a noncanonical inflammasome has been characterized which functions through caspase 11 and appears to augment many biological functions previously considered to be dependent upon the canonical inflammasome. To better elucidate the function of this noncanonical inflammasome in toxoplasmosis, we utilized Asc (-/-) and Casp11 (-/-) mice and infected these animals with T. gondii. Our data indicates that caspase-11 modulates the innate immune response to T. gondii through a mechanism which is distinct from that currently described for the canonical inflammasome. Asc (-/-) mice demonstrated increased disease pathogenesis during the acute phase of T. gondii infection, whereas Casp11 (-/-) mice demonstrated significantly attenuated disease pathogenesis and reduced inflammation. This attenuated host response was associated with reduced local and systemic cytokine production, including diminished IL-1beta. During the chronic phase of infection, caspase-11 deficiency resulted in increased neuroinflammation and tissue cyst burden in the brain. Together, our data suggest that caspase-11 functions to protect the host by enhancing inflammation during the early phase of infection in an effort to minimize disease pathogenesis during later stages of toxoplasmosis. PMID- 27378828 TI - Long-Term Endoscopic Follow-Up of Patients with Chronic Radiation Proctopathy after Brachytherapy for Prostate Cancer. AB - Background. Chronic radiation proctopathy (CRP) is late toxicity and associated with morbidity. Aim. To investigate the predictors of prognosis in patients with CRP after brachytherapy (BT). Methods. One hundred four patients with prostate cancer were treated with BT or BT followed by external-beam radiotherapy (BT + EBRT). We retrospectively investigated the 5-year incidence of rectal bleeding and endoscopic findings of CRP using the Vienna Rectoscopy Score (VRS). Twenty patients with VRS >= 1 were divided into the improved VRS group without treatment, unchanged VRS group, and treated group. The parameters associated with alteration of VRS were analyzed. Results. The incidence of rectal bleeding was 24%. The risk of rectal bleeding was higher in patients treated with BT + EBRT compared to those treated with BT (p < 0.0001). The incidence of superficial microulceration was higher in the improved VRS group than in the unchanged VRS group (p < 0.05). The incidence of multiple confluent telangiectasia or superficial ulcers > 1 cm(2) was higher in the treated group than in both the improved and unchanged VRS groups (p < 0.05). Conclusions. Patients treated with BT + EBRT have a high risk of CRP. Endoscopic findings were useful for prognostic prediction of CRP. PMID- 27378829 TI - Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma. AB - Skeletal muscle atrophy in cancer cachexia is mediated by the interaction between muscle stem cells and various tumor factors. Although Notch signaling has been known as a key regulator of both cancer development and muscle stem cell activity, the potential involvement of Notch signaling in cancer cachexia and concomitant muscle atrophy has yet to be elucidated. The murine K7M2 osteosarcoma cell line was used to generate an orthotopic model of sarcoma-associated cachexia, and the role of Notch signaling was evaluated. Skeletal muscle atrophy was observed in the sarcoma-bearing mice, and Notch signaling was highly active in both tumor tissues and the atrophic skeletal muscles. Systemic inhibition of Notch signaling reduced muscle atrophy. In vitro coculture of osteosarcoma cells with muscle-derived stem cells (MDSCs) isolated from normal mice resulted in decreased myogenic potential of MDSCs, while the application of Notch inhibitor was able to rescue this repressed myogenic potential. We further observed that Notch-activating factors reside in the exosomes of osteosarcoma cells, which activate Notch signaling in MDSCs and subsequently repress myogenesis. Our results revealed that signaling between tumor and muscle via the Notch pathway may play an important role in mediating the skeletal muscle atrophy seen in cancer cachexia. PMID- 27378830 TI - An Examination of Interactions between Hospice Health Care Providers and Adolescents with a Parent in Hospice. AB - Interviews conducted with adolescents living with a dying parent were examined to identify the type of interactions the adolescents had with members of a hospice healthcare team. Four types of interactions were identified: No Interactions, In passing Interactions, Engaged Interactions, and Formal Interactions. Results indicated that most of the adolescents had no contact with the hospice healthcare team or interacted with providers only briefly. Some adolescents reported more engagement with one or more hospice healthcare team members, and a few received formal counseling services from the hospice healthcare team or outside provider. Overall, limited contact occurred because of logistics or because the teens perceived that hospice services were exclusively targeted to dying patients, not their families. Based on these findings, strategies to increase engagement between adolescents and hospice healthcare team are discussed. PMID- 27378831 TI - Effects of Body Mass Index and Body Fat Percent on Default Mode, Executive Control, and Salience Network Structure and Function. AB - It is well established that obesity decreases overall life expectancy and increases the risk of several adverse health conditions. Mounting evidence indicates that body fat is likely also associated with structural and functional brain changes, reduced cognitive function, and greater impulsivity. However, previously reported differences in brain structure and function have been variable across studies and difficult to reconcile due to sample population and methodological differences. To clarify these issues, we correlated two independent measures of body composition-i.e., body mass index (BMI) and body fat percent (BFP)-with structural and functional neuroimaging data obtained from a cohort of 32 neurologically healthy adults. Whole-brain voxel-wise analyses indicated that higher BMI and BFP were associated with widespread decreases in gray matter volume, white matter volume, and white matter microstructure (including several regions, such as the striatum and orbitofrontal cortex, which may influence value assessment, habit formation, and decision-making). Moreover, closer examination of resting state functional connectivity, white matter volume, and white matter microstructure throughout the default mode network (DMN), executive control network (ECN), and salience network (SN) revealed that higher BMI and BFP were associated with increased SN functional connectivity and decreased white matter volumes throughout all three networks (i.e., the DMN, ECN, and SN). Taken together, these findings: (1) offer a biologically plausible explanation for reduced cognitive performance, greater impulsivity, and altered reward processing among overweight individuals, and (2) suggest neurobiological mechanisms (i.e., altered functional and structural brain connectivity) that may affect overweight individuals' ability to establish and maintain healthy lifestyle choices. PMID- 27378833 TI - Temporally Regular Musical Primes Facilitate Subsequent Syntax Processing in Children with Specific Language Impairment. AB - Children with developmental language disorders have been shown to be also impaired in rhythm and meter perception. Temporal processing and its link to language processing can be understood within the dynamic attending theory. An external stimulus can stimulate internal oscillators, which orient attention over time and drive speech signal segmentation to provide benefits for syntax processing, which is impaired in various patient populations. For children with Specific Language Impairment (SLI) and dyslexia, previous research has shown the influence of an external rhythmic stimulation on subsequent language processing by comparing the influence of a temporally regular musical prime to that of a temporally irregular prime. Here we tested whether the observed rhythmic stimulation effect is indeed due to a benefit provided by the regular musical prime (rather than a cost subsequent to the temporally irregular prime). Sixteen children with SLI and 16 age-matched controls listened to either a regular musical prime sequence or an environmental sound scene (without temporal regularities in event occurrence; i.e., referred to as "baseline condition") followed by grammatically correct and incorrect sentences. They were required to perform grammaticality judgments for each auditorily presented sentence. Results revealed that performance for the grammaticality judgments was better after the regular prime sequences than after the baseline sequences. Our findings are interpreted in the theoretical framework of the dynamic attending theory (Jones, 1976) and the temporal sampling (oscillatory) framework for developmental language disorders (Goswami, 2011). Furthermore, they encourage the use of rhythmic structures (even in non-verbal materials) to boost linguistic structure processing and outline perspectives for rehabilitation. PMID- 27378834 TI - The Indris Have Got Rhythm! Timing and Pitch Variation of a Primate Song Examined between Sexes and Age Classes. AB - A crucial, common feature of speech and music is that they show non-random structures over time. It is an open question which of the other species share rhythmic abilities with humans, but in most cases the lack of knowledge about their behavioral displays prevents further studies. Indris are the only lemurs who sing. They produce loud howling cries that can be heard at several kilometers, in which all members of a group usually sing. We tested whether overlapping and turn-taking during the songs followed a precise pattern by analysing the temporal structure of the individuals' contribution to the song. We found that both dominants (males and females) and non-dominants influenced the onset timing one another. We have found that the dominant male and the dominant female in a group overlapped each other more frequently than they did with the non-dominants. We then focused on the temporal and frequency structure of particular phrases occurring during the song. Our results show that males and females have dimorphic inter-onset intervals during the phrases. Moreover, median frequencies of the unit emitted in the phrases also differ between the sexes, with males showing higher frequencies when compared to females. We have not found an effect of age on the temporal and spectral structure of the phrases. These results indicate that singing in indris has a high behavioral flexibility and varies according to social and individual factors. The flexible spectral structure of the phrases given during the song may underlie perceptual abilities that are relatively unknown in other non-human primates, such as the ability to recognize particular pitch patterns. PMID- 27378835 TI - Monitoring of Tumor Growth with [(18)F]-FET PET in a Mouse Model of Glioblastoma: SUV Measurements and Volumetric Approaches. AB - Noninvasive tumor growth monitoring is of particular interest for the evaluation of experimental glioma therapies. This study investigates the potential of positron emission tomography (PET) using O-(2-(18)F-fluoroethyl)-L-tyrosine ([(18)F]-FET) to determine tumor growth in a murine glioblastoma (GBM) model including estimation of the biological tumor volume (BTV), which has hitherto not been investigated in the pre-clinical context. Fifteen GBM-bearing mice (GL261) and six control mice (shams) were investigated during 5 weeks by PET followed by autoradiographic and histological assessments. [(18)F]-FET PET was quantitated by calculation of maximum and mean standardized uptake values within a universal volume-of-interest (VOI) corrected for healthy background (SUVmax/BG, SUVmean/BG). A partial volume effect correction (PVEC) was applied in comparison to ex vivo autoradiography. BTVs obtained by predefined thresholds for VOI definition (SUV/BG: >=1.4; >=1.6; >=1.8; >=2.0) were compared to the histologically assessed tumor volume (n = 8). Finally, individual "optimal" thresholds for BTV definition best reflecting the histology were determined. In GBM mice SUVmax/BG and SUVmean/BG clearly increased with time, however at high inter-animal variability. No relevant [(18)F]-FET uptake was observed in shams. PVEC recovered signal loss of SUVmean/BG assessment in relation to autoradiography. BTV as estimated by predefined thresholds strongly differed from the histology volume. Strikingly, the individual "optimal" thresholds for BTV assessment correlated highly with SUVmax/BG (rho = 0.97, p < 0.001), allowing SUVmax/BG-based calculation of individual thresholds. The method was verified by a subsequent validation study (n = 15, rho = 0.88, p < 0.01) leading to extensively higher agreement of BTV estimations when compared to histology in contrast to predefined thresholds. [(18)F]-FET PET with standard SUV measurements is feasible for glioma imaging in the GBM mouse model. PVEC is beneficial to improve accuracy of [(18)F]-FET PET SUV quantification. Although SUVmax/BG and SUVmean/BG increase during the disease course, these parameters do not correlate with the respective tumor size. For the first time, we propose a histology verified method allowing appropriate individual BTV estimation for volumetric in vivo monitoring of tumor growth with [(18)F]-FET PET and show that standardized thresholds from routine clinical practice seem to be inappropriate for BTV estimation in the GBM mouse model. PMID- 27378832 TI - Functional Zonation of the Adult Mammalian Adrenal Cortex. AB - The standard model of adrenocortical zonation holds that the three main zones, glomerulosa, fasciculata, and reticularis each have a distinct function, producing mineralocorticoids (in fact just aldosterone), glucocorticoids, and androgens respectively. Moreover, each zone has its specific mechanism of regulation, though ACTH has actions throughout. Finally, the cells of the cortex originate from a stem cell population in the outer cortex or capsule, and migrate centripetally, changing their phenotype as they progress through the zones. Recent progress in understanding the development of the gland and the distribution of steroidogenic enzymes, trophic hormone receptors, and other factors suggests that this model needs refinement. Firstly, proliferation can take place throughout the gland, and although the stem cells are certainly located in the periphery, zonal replenishment can take place within zones. Perhaps more importantly, neither the distribution of enzymes nor receptors suggest that the individual zones are necessarily autonomous in their production of steroid. This is particularly true of the glomerulosa, which does not seem to have the full suite of enzymes required for aldosterone biosynthesis. Nor, in the rat anyway, does it express MC2R to account for the response of aldosterone to ACTH. It is known that in development, recruitment of stem cells is stimulated by signals from within the glomerulosa. Furthermore, throughout the cortex local regulatory factors, including cytokines, catecholamines and the tissue renin angiotensin system, modify and refine the effects of the systemic trophic factors. In these and other ways it more and more appears that the functions of the gland should be viewed as an integrated whole, greater than the sum of its component parts. PMID- 27378836 TI - Computational Pipeline for NIRS-EEG Joint Imaging of tDCS-Evoked Cerebral Responses-An Application in Ischemic Stroke. AB - Transcranial direct current stimulation (tDCS) modulates cortical neural activity and hemodynamics. Electrophysiological methods (electroencephalography-EEG) measure neural activity while optical methods (near-infrared spectroscopy-NIRS) measure hemodynamics coupled through neurovascular coupling (NVC). Assessment of NVC requires development of NIRS-EEG joint-imaging sensor montages that are sensitive to the tDCS affected brain areas. In this methods paper, we present a software pipeline incorporating freely available software tools that can be used to target vascular territories with tDCS and develop a NIRS-EEG probe for joint imaging of tDCS-evoked responses. We apply this software pipeline to target primarily the outer convexity of the brain territory (superficial divisions) of the middle cerebral artery (MCA). We then present a computational method based on Empirical Mode Decomposition of NIRS and EEG time series into a set of intrinsic mode functions (IMFs), and then perform a cross-correlation analysis on those IMFs from NIRS and EEG signals to model NVC at the lesional and contralesional hemispheres of an ischemic stroke patient. For the contralesional hemisphere, a strong positive correlation between IMFs of regional cerebral hemoglobin oxygen saturation and the log-transformed mean-power time-series of IMFs for EEG with a lag of about -15 s was found after a cumulative 550 s stimulation of anodal tDCS. It is postulated that system identification, for example using a continuous-time autoregressive model, of this coupling relation under tDCS perturbation may provide spatiotemporal discriminatory features for the identification of ischemia. Furthermore, portable NIRS-EEG joint imaging can be incorporated into brain computer interfaces to monitor tDCS-facilitated neurointervention as well as cortical reorganization. PMID- 27378837 TI - Benefits of Stimulus Exposure: Developmental Learning Independent of Task Performance. AB - Perceptual learning (training-induced performance improvement) can be elicited by task-irrelevant stimulus exposure in humans. In contrast, task-irrelevant stimulus exposure in animals typically disrupts perception in juveniles while causing little to no effect in adults. This may be due to the extent of exposure, which is brief in humans while chronic in animals. Here we assessed the effects of short bouts of passive stimulus exposure on learning during development in gerbils, compared with non-passive stimulus exposure (i.e., during testing). We used prepulse inhibition of the acoustic startle response, a method that can be applied at any age, to measure gap detection thresholds across four age groups, spanning development. First, we showed that both gap detection thresholds and gap detection learning across sessions displayed a long developmental trajectory, improving throughout the juvenile period. Additionally, we demonstrated larger within- and across-animal performance variability in younger animals. These results are generally consistent with results in humans, where there are extended developmental trajectories for both the perception of temporally-varying signals, and the effects of perceptual training, as well as increased variability and poorer performance consistency in children. We then chose an age (mid-juveniles) that displayed clear learning over sessions in order to assess effects of brief passive stimulus exposure on this learning. We compared learning in mid-juveniles exposed to either gap detection testing (gaps paired with startles) or equivalent gap exposure without testing (gaps alone) for three sessions. Learning was equivalent in both these groups and better than both naive age-matched animals and controls receiving no gap exposure but only startle testing. Thus, short bouts of exposure to gaps independent of task performance is sufficient to induce learning at this age, and is as effective as gap detection testing. PMID- 27378839 TI - Testable Hypotheses for Unbalanced Neuroimaging Data. AB - Unbalanced group-level models are common in neuroimaging. Typically, data for these models come from factorial experiments. As such, analyses typically take the form of an analysis of variance (ANOVA) within the framework of the general linear model (GLM). Although ANOVA theory is well established for the balanced case, in unbalanced designs there are multiple ways of decomposing the sums-of squares of the data. This leads to several methods of forming test statistics when the model contains multiple factors and interactions. Although the Type I III sums of squares have a long history of debate in the statistical literature, there has seemingly been no consideration of this aspect of the GLM in neuroimaging. In this paper we present an exposition of these different forms of hypotheses for the neuroimaging researcher, discussing their derivation as estimable functions of ANOVA models, and discussing the relative merits of each. Finally, we demonstrate how the different hypothesis tests can be implemented using contrasts in analysis software, presenting examples in SPM and FSL. PMID- 27378838 TI - Toward an Interdisciplinary Understanding of Sensory Dysfunction in Autism Spectrum Disorder: An Integration of the Neural and Symptom Literatures. AB - Sensory processing differences have long been associated with autism spectrum disorder (ASD), and they have recently been added to the diagnostic criteria for the disorder. The focus on sensory processing in ASD research has increased substantially in the last decade. This research has been approached from two different perspectives: the first focuses on characterizing the symptoms that manifest in response to real world sensory stimulation, and the second focuses on the neural pathways and mechanisms underlying sensory processing. The purpose of this paper is to integrate the empirical literature on sensory processing in ASD from the last decade, including both studies characterizing sensory symptoms and those that investigate neural response to sensory stimuli. We begin with a discussion of definitions to clarify some of the inconsistencies in terminology that currently exist in the field. Next, the sensory symptoms literature is reviewed with a particular focus on developmental considerations and the relationship of sensory symptoms to other core features of the disorder. Then, the neuroscience literature is reviewed with a focus on methodological approaches and specific sensory modalities. Currently, these sensory symptoms and neuroscience perspectives are largely developing independently from each other leading to multiple, but separate, theories and methods, thus creating a multidisciplinary approach to sensory processing in ASD. In order to progress our understanding of sensory processing in ASD, it is now critical to integrate these two research perspectives and move toward an interdisciplinary approach. This will inevitably aid in a better understanding of the underlying biological basis of these symptoms and help realize the translational value through its application to early identification and treatment. The review ends with specific recommendations for future research to help bridge these two research perspectives in order to advance our understanding of sensory processing in ASD. PMID- 27378840 TI - Implications of Oxytocin in Human Linguistic Cognition: From Genome to Phenome. AB - The neurohormone oxytocin (OXT) has been found to mediate the regulation of complex socioemotional cognition in multiple ways both in humans and other animals. Recent studies have investigated the effects of OXT in different levels of analysis (from genetic to behavioral) chiefly targeting its impact on the social component and only indirectly indicating its implications in other components of our socio-interactive abilities. This article aims at shedding light onto how OXT might be modulating the multimodality that characterizes our higher-order linguistic abilities (vocal-auditory-attentional-memory-social systems). Based on evidence coming from genetic, EEG, fMRI, and behavioral studies, I attempt to establish the promises of this perspective with the goal of stressing the need for neuropeptide treatments to enter clinical practice. PMID- 27378841 TI - Beyond the Metronome: Auditory Events and Music May Afford More than Just Interval Durations as Gait Cues in Parkinson's Disease. PMID- 27378842 TI - Qualitative-Modeling-Based Silicon Neurons and Their Networks. AB - The ionic conductance models of neuronal cells can finely reproduce a wide variety of complex neuronal activities. However, the complexity of these models has prompted the development of qualitative neuron models. They are described by differential equations with a reduced number of variables and their low dimensional polynomials, which retain the core mathematical structures. Such simple models form the foundation of a bottom-up approach in computational and theoretical neuroscience. We proposed a qualitative-modeling-based approach for designing silicon neuron circuits, in which the mathematical structures in the polynomial-based qualitative models are reproduced by differential equations with silicon-native expressions. This approach can realize low-power-consuming circuits that can be configured to realize various classes of neuronal cells. In this article, our qualitative-modeling-based silicon neuron circuits for analog and digital implementations are quickly reviewed. One of our CMOS analog silicon neuron circuits can realize a variety of neuronal activities with a power consumption less than 72 nW. The square-wave bursting mode of this circuit is explained. Another circuit can realize Class I and II neuronal activities with about 3 nW. Our digital silicon neuron circuit can also realize these classes. An auto-associative memory realized on an all-to-all connected network of these silicon neurons is also reviewed, in which the neuron class plays important roles in its performance. PMID- 27378843 TI - What Pinnipeds Have to Say about Human Speech, Music, and the Evolution of Rhythm. AB - Research on the evolution of human speech and music benefits from hypotheses and data generated in a number of disciplines. The purpose of this article is to illustrate the high relevance of pinniped research for the study of speech, musical rhythm, and their origins, bridging and complementing current research on primates and birds. We briefly discuss speech, vocal learning, and rhythm from an evolutionary and comparative perspective. We review the current state of the art on pinniped communication and behavior relevant to the evolution of human speech and music, showing interesting parallels to hypotheses on rhythmic behavior in early hominids. We suggest future research directions in terms of species to test and empirical data needed. PMID- 27378844 TI - Bio-Inspired Controller on an FPGA Applied to Closed-Loop Diaphragmatic Stimulation. AB - Cervical spinal cord injury can disrupt connections between the brain respiratory network and the respiratory muscles which can lead to partial or complete loss of ventilatory control and require ventilatory assistance. Unlike current open-loop technology, a closed-loop diaphragmatic pacing system could overcome the drawbacks of manual titration as well as respond to changing ventilation requirements. We present an original bio-inspired assistive technology for real time ventilation assistance, implemented in a digital configurable Field Programmable Gate Array (FPGA). The bio-inspired controller, which is a spiking neural network (SNN) inspired by the medullary respiratory network, is as robust as a classic controller while having a flexible, low-power and low-cost hardware design. The system was simulated in MATLAB with FPGA-specific constraints and tested with a computational model of rat breathing; the model reproduced experimentally collected respiratory data in eupneic animals. The open-loop version of the bio-inspired controller was implemented on the FPGA. Electrical test bench characterizations confirmed the system functionality. Open and closed loop paradigm simulations were simulated to test the FPGA system real-time behavior using the rat computational model. The closed-loop system monitors breathing and changes in respiratory demands to drive diaphragmatic stimulation. The simulated results inform future acute animal experiments and constitute the first step toward the development of a neuromorphic, adaptive, compact, low power, implantable device. The bio-inspired hardware design optimizes the FPGA resource and time costs while harnessing the computational power of spike-based neuromorphic hardware. Its real-time feature makes it suitable for in vivo applications. PMID- 27378845 TI - Structural Studies of GABAA Receptor Binding Sites: Which Experimental Structure Tells us What? AB - Atomic resolution structures of cys-loop receptors, including one of a gamma aminobutyric acid type A receptor (GABAA receptor) subtype, allow amazing insights into the structural features and conformational changes that these pentameric ligand-gated ion channels (pLGICs) display. Here we present a comprehensive analysis of more than 30 cys-loop receptor structures of homologous proteins that revealed several allosteric binding sites not previously described in GABAA receptors. These novel binding sites were examined in GABAA receptor homology models and assessed as putative candidate sites for allosteric ligands. Four so far undescribed putative ligand binding sites were proposed for follow up studies based on their presence in the GABAA receptor homology models. A comprehensive analysis of conserved structural features in GABAA and glycine receptors (GlyRs), the glutamate gated ion channel, the bacterial homologs Erwinia chrysanthemi (ELIC) and Gloeobacter violaceus GLIC, and the serotonin type 3 (5-HT3) receptor was performed. The conserved features were integrated into a master alignment that led to improved homology models. The large fragment of the intracellular domain that is present in the structure of the 5-HT3 receptor was utilized to generate GABAA receptor models with a corresponding intracellular domain fragment. Results of mutational and photoaffinity ligand studies in GABAA receptors were analyzed in the light of the model structures. This led to an assignment of candidate ligands to two proposed novel pockets, candidate binding sites for furosemide and neurosteroids in the trans-membrane domain were identified. The homology models can serve as hypotheses generators, and some previously controversial structural interpretations of biochemical data can be resolved in the light of the presented multi-template approach to comparative modeling. Crystal and cryo-EM microscopic structures of the closest homologs that were solved in different conformational states provided important insights into structural rearrangements of binding sites during conformational transitions. The impact of structural variation and conformational motion on the shape of the investigated binding sites was analyzed. Rules for best template and alignment choice were obtained and can generally be applied to modeling of cys loop receptors. Overall, we provide an updated structure based view of ligand binding sites present in GABAA receptors. PMID- 27378846 TI - Inter- and Intra-Subunit Butanol/Isoflurane Sites of Action in the Human Glycine Receptor. AB - Glycine receptors (GlyRs) mediate inhibitory neurotransmission and are targets for alcohols and anesthetics in brain. GlyR transmembrane (TM) domains contain critical residues for alcohol/anesthetic action: amino acid A288 in TM3 forms crosslinks with TM1 (I229) in the adjacent subunit as well as TM2 (S267) and TM4 (Y406, W407, I409, Y410) in the same subunit. We hypothesized that these residues may participate in intra-subunit and inter-subunit sites of alcohol/anesthetic action. The following double and triple mutants of GLRA1 cDNA (encoding human glycine receptor alpha 1 subunit) were injected into Xenopus laevis oocytes: I229C/A288C, I229C/A288C/C290S, A288C/Y406C, A288C/W407C, A288C/I409C, and A288C/Y410C along with the corresponding single mutants and wild-type GLRA1. Butanol (22 mM) or isoflurane (0.6 mM) potentiation of GlyR-mediated currents before and after application of the cysteine crosslinking agent HgCl2 (10 MUM) was measured using two-electrode voltage clamp electrophysiology. Crosslinking nearly abolished butanol and isoflurane potentiation in the I229C/A288C and I229C/A288C/C290S mutants but had no effect in single mutants or wild-type. Crosslinking also inhibited butanol and isoflurane potentiation in the TM3-4 mutants (A288C/Y406C, A288C/W407C, A288C/I409C, A288C/Y410C) with no effect in single mutants or wild-type. We extracted proteins from oocytes expressing I229C/288C, A288C/Y410C, or wild-type GlyRs, used mass spectrometry to verify their expression and possible inter-subunit dimerization, plus immunoblotting to investigate the biochemical features of proposed crosslinks. Wild-type GlyR subunits measured about 50 kDa; after crosslinking, the dimeric/monomeric 100:50 kDa band ratio was significantly increased in I229C/288C but not A288C/Y410C mutants or wild-type, providing support for TM1-3 inter-subunit and TM3-4 intra subunit crosslinking. A GlyR homology model based on the GluCl template provides further evidence for a multi-site model for alcohol/anesthetic interaction with human GLRA1. PMID- 27378848 TI - Versatile Structures of alpha-Synuclein. AB - alpha-Synuclein (alpha-syn) is an intrinsically disordered protein abundantly distributed in presynaptic terminals. Aggregation of alpha-syn into Lewy bodies (LB) is a molecular hallmark of Parkinson's disease (PD). alpha-Syn features an extreme conformational diversity, which adapts to different conditions and fulfills versatile functions. However, the molecular mechanism of alpha-syn transformation and the relation between different structural species and their functional and pathogenic roles in neuronal activities and PD remain unknown. In this mini-review, we summarize the recent discoveries of alpha-syn structures in the membrane-bound state, in cytosol, and in the amyloid state under physiological and pathological conditions. From the current knowledge on different structural species of alpha-syn, we intend to find a clue about its function and toxicity in normal neurons and under disease conditions, which could shed light on the PD pathogenesis. PMID- 27378847 TI - Energy and Potassium Ion Homeostasis during Gamma Oscillations. AB - Fast neuronal network oscillations in the gamma frequency band (30-100 Hz) occur in various cortex regions, require timed synaptic excitation and inhibition with glutamate and GABA, respectively, and are associated with higher brain functions such as sensory perception, attentional selection and memory formation. However, little is known about energy and ion homeostasis during the gamma oscillation. Recent studies addressed this topic in slices of the rodent hippocampus using cholinergic and glutamatergic receptor models of gamma oscillations (GAM). Methods with high spatial and temporal resolution were applied in vitro, such as electrophysiological recordings of local field potential (LFP) and extracellular potassium concentration ([K(+)]o), live-cell fluorescence imaging of nicotinamide adenine dinucleotide (phosphate) and flavin adenine dinucleotide [NAD(P)H and FAD, respectively] (cellular redox state), and monitoring of the interstitial partial oxygen pressure (pO2) in depth profiles with microsensor electrodes, including mathematical modeling. The main findings are: (i) GAM are associated with high oxygen consumption rate and significant changes in the cellular redox state, indicating rapid adaptations in glycolysis and oxidative phosphorylation; (ii) GAM are accompanied by fluctuating elevations in [K(+)]o of less than 0.5 mmol/L from baseline, likely reflecting effective K(+)-uptake mechanisms of neuron and astrocyte compartments; and (iii) GAM are exquisitely sensitive to metabolic stress induced by lowering oxygen availability or by pharmacological inhibition of the mitochondrial respiratory chain. These findings reflect precise cellular adaptations to maintain adenosine-5'-triphosphate (ATP), ion and neurotransmitter homeostasis and thus neural excitability and synaptic signaling during GAM. Conversely, the exquisite sensitivity of GAM to metabolic stress might significantly contribute the exceptional vulnerability of higher brain functions in brain disease. PMID- 27378849 TI - Enhanced Immune Response in Immunodeficient Mice Improves Peripheral Nerve Regeneration Following Axotomy. AB - Injuries to peripheral nerves cause loss of motor and sensory function, greatly affecting life quality. Successful repair of the lesioned nerve requires efficient cell debris removal, followed by axon regeneration and reinnervation of target organs. Such process is orchestrated by several cellular and molecular events in which glial and immune cells actively participate. It is known that tissue clearance is largely improved by macrophages, which activation is potentiated by cells and molecules of the acquired immune system, such as T helper lymphocytes and antibodies, respectively. In the present work, we evaluated the contribution of lymphocytes in the regenerative process of crushed sciatic nerves of immunocompetent (wild-type, WT) and T and B-deficient (RAG-KO) mice. In Knockout animals, we found increased amount of macrophages under basal conditions and during the initial phase of the regenerative process, that was evaluated at 2, 4, and 8 weeks after lesion (wal). That parallels with faster axonal regeneration evidenced by the quantification of neurofilament and a growth associated protein immunolabeling. The motor function, evaluated by the sciatic function index, was fully recovered in both mouse strains within 4 wal, either in a progressive fashion, as observed for RAG-KO mice, or presenting a subtle regression, as seen in WT mice between 2 and 3 wal. Interestingly, boosting the immune response by early adoptive transference of activated WT lymphocytes at 3 days after lesion improved motor recovery in WT and RAG-KO mice, which was not ameliorated when cells were transferred at 2 wal. When monitoring lymphocytes by in vivo imaging, in both mouse strains, cells migrated to the lesion site shortly after transference, remaining in the injured limb up to its complete motor recovery. Moreover, a first peak of hyperalgesia, determined by von-Frey test, was coincident with increased lymphocyte infiltration in the damaged paw. Overall, the present results suggest that a wave of immune cell infiltration takes place during subacute phase of axonal regeneration, resulting in transient set back of motor recovery following peripheral axonal injury. Moreover, modulation of the immune response can be an efficient approach to speed up nerve regeneration. PMID- 27378850 TI - A Novel Form of Compensation in the Tg2576 Amyloid Mouse Model of Alzheimer's Disease. AB - One century after its first description, pathology of Alzheimer's disease (AD) is still poorly understood. Amyloid-related dendritic atrophy and membrane alterations of susceptible brain neurons in AD, and in animal models of AD are widely recognized. However, little effort has been made to study the potential effects of combined morphological and membrane alterations on signal transfer and synaptic integration in neurons that build up affected neural networks in AD. In this study spatial reconstructions and electrophysiological measurements of layer II/III pyramidal neurons of the somatosensory cortex from wild-type (WT) and transgenic (TG) human amyloid precursor protein (hAPP) overexpressing Tg2576 mice were used to build faithful segmental cable models of these neurons. Local synaptic activities were simulated in various points of the dendritic arbors and properties of subthreshold dendritic impulse propagation and predictors of synaptic input pattern recognition ability were quantified and compared in modeled WT and TG neurons. Despite the widespread dendritic degeneration and membrane alterations in mutant mouse neurons, surprisingly little, or no change was detected in steady-state and 50 Hz sinusoidal voltage transfers, current transfers, and local and propagation delays of PSPs traveling along dendrites of TG neurons. Synaptic input pattern recognition ability was also predicted to be unaltered in TG neurons in two different soma-dendritic membrane models investigated. Our simulations predict the way how subthreshold dendritic signaling and pattern recognition are preserved in TG neurons: amyloid-related membrane alterations compensate for the pathological effects that dendritic atrophy has on subthreshold dendritic signal transfer and integration in layer II/III somatosensory neurons of this hAPP mouse model for AD. Since neither propagation of single PSPs nor integration of multiple PSPs (pattern recognition) changes in TG neurons, we conclude that AD-related neuronal hyperexcitability cannot be accounted for by altered subthreshold dendritic signaling in these neurons but hyperexcitability is related to changes in active membrane properties and network connectivity. PMID- 27378851 TI - Neuroserpin Differentiates Between Forms of Tissue Type Plasminogen Activator via pH Dependent Deacylation. AB - Tissue-type plasminogen activator (t-PA), initially characterized for its critical role in fibrinolysis, also has key functions in both physiologic and pathologic processes in the CNS. Neuroserpin (NSP) is a t-PA specific serine protease inhibitor (serpin) found almost exclusively in the CNS that regulates t PA's proteolytic activity and protects against t-PA mediated seizure propagation and blood-brain barrier disruption. This report demonstrates that NSP inhibition of t-PA varies profoundly as a function of pH within the biologically relevant pH range for the CNS, and reflects the stability, rather than the formation of NSP: t-PA acyl-enzyme complexes. Moreover, NSP differentiates between the zymogen-like single chain form (single chain t-PA, sct-PA) and the mature protease form (two chain t-PA, tct-PA) of t-PA, demonstrating different pH profiles for protease inhibition, different pH ranges over which catalytic deacylation occurs, and different pH dependent profiles of deacylation rates for each form of t-PA. NSP's pH dependent inhibition of t-PA is not accounted for by differential acylation, and is specific for the NSP-t-PA serpin-protease pair. These results demonstrate a novel mechanism for the differential regulation of the two forms of t-PA in the CNS, and suggest a potential specific regulatory role for CNS pH in controlling t PA proteolytic activity. PMID- 27378852 TI - Social Isolation Blunted the Response of Mesocortical Dopaminergic Neurons to Chronic Ethanol Voluntary Intake. AB - Previous studies have shown that stress can increase the response of mesolimbic dopaminergic neurons to acute administration of drugs of abuse included ethanol. In this study, we investigated the possible involvement of the mesocortical dopaminergic pathway in the development of ethanol abuse under stress conditions. To this aim we trained both socially isolated (SI) and group housed (GH) rats to self administer ethanol which was made available only 2 ha day (from 11:00 to 13:00 h). Rats have been trained for 3 weeks starting at postnatal day 35. After training, rats were surgically implanted with microdialysis probes under deep anesthesia, and 24 hlater extracellular dopamine concentrations were monitored in medial prefrontal cortex (mPFC) for the 2 hpreceding ethanol administration (anticipatory phase), during ethanol exposure (consummatory phase) and for 2 hafter ethanol removal. Results show that, in GH animals, dopamine extracellular concentration in the mPFC increased as early as 80 min before ethanol presentation (+50% over basal values) and remained elevated for 80 min during ethanol exposure. In SI rats, on the contrary, dopamine extracellular concentration did not show any significant change at any time point. Ethanol consumption was significantly higher in SI than in GH rats. Moreover, mesocortical dopaminergic neurons in SI animals also showed a decreased sensitivity to an acute administration of ethanol with respect to GH rats. Our results show that prolonged exposure to stress, as in social isolation, is able to induce significant changes in the response of mesocortical dopaminergic neurons to ethanol exposure and suggest that these changes might play an important role in the compulsivity observed in ethanol addiction. PMID- 27378853 TI - The Revolution in Migraine Genetics: From Aching Channels Disorders to a Next Generation Medicine. AB - Channelopathies are a heterogeneous group of neurological disorders resulting from dysfunction of ion channels located in cell membranes and organelles. The clinical scenario is broad and symptoms such as generalized epilepsy (with or without fever), migraine (with or without aura), episodic ataxia and periodic muscle paralysis are some of the best known consequences of gain- or loss-of function mutations in ion channels. We review the main clinical effects of ion channel mutations associated with a significant impact on migraine headache. Given the increasing and evolving use of genetic analysis in migraine research greater emphasis is now placed on genetic markers of dysfunctional biological systems-we also show how novel information in rare monogenic forms of migraine might help to clarify the disease mechanisms in the general population of migraineurs. Next-generation sequencing (NGS) and more accurate and precise phenotyping strategies are expected to further increase understanding of migraine pathophysiology and genetics. PMID- 27378854 TI - Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function. AB - The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID- 27378855 TI - Isolation Rearing Reduces Neuronal Excitability in Dentate Gyrus Granule Cells of Adolescent C57BL/6J Mice: Role of GABAergic Tonic Currents and Neurosteroids. AB - Early-life exposure to stress, by impacting on a brain still under development, is considered a critical factor for the increased vulnerability to psychiatric disorders and abuse of psychotropic substances during adulthood. As previously reported, rearing C57BL/6J weanling mice in social isolation (SI) from their peers for several weeks, a model of prolonged stress, is associated with a decreased plasma and brain levels of neuroactive steroids such as 3alpha,5alpha THP, with a parallel up-regulation of extrasynaptic GABAA receptors (GABAAR) in dentate gyrus (DG) granule cells compared to group-housed (GH) mice. In the present study, together with the SI-induced decrease in plasma concentration of both progesterone and 3alpha,5alpha-THP, and an increase in THIP-stimulated GABAergic tonic currents, patch-clamp analysis of DG granule cells revealed a significant decrease in membrane input resistance and action potential (AP) firing rate, in SI compared to GH mice, suggesting that SI exerts an inhibitory action on neuronal excitability of these neurons. Voltage-clamp recordings of glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs) revealed a SI associated decrease in frequency as well as a shift from paired-pulse (PP) depression to PP facilitation (PPF) of evoked EPSCs, indicative of a reduced probability of glutamate release. Daily administration of progesterone during isolation reverted the changes in plasma 3alpha,5alpha-THP as well as in GABAergic tonic currents and neuronal excitability caused by SI, but it had only a limited effect on the changes in the probability of presynaptic glutamate release. Overall, the results obtained in this work, together with those previously published, indicate that exposure of mice to SI during adolescence reduces neuronal excitability of DG granule cells, an effect that may be linked to the increased GABAergic tonic currents as a consequence of the sustained decrease in plasma and hippocampal levels of neurosteroids. All these changes may be consistent with cognitive deficits observed in animals exposed to such type of prolonged stress. PMID- 27378856 TI - Controlling the Emotional Bias: Performance, Late Positive Potentials, and the Effect of Anodal Transcranial Direct Current Stimulation (tDCS). AB - Cognitive control of emotional processing is essential for adaptive human behavior. Biased attention toward emotionally salient information is critically linked with affective disorders and is discussed as a promising treatment target. Anodal (activity enhancing) transcranial direct current stimulation (tDCS) has been shown to increase healthy and impaired cognitive control over emotional distraction and is therefore widely used for the investigation and experimental treatment of this disorder. In this study, event-related potential (ERP) were recorded parallel to tDCS to track its online effects. Healthy volunteers (n = 87) performed a delayed working memory paradigm with emotional salient and neutral distractors during stimulation with different intensities (sham, 0.5, 1, 1.5 mA). Measuring the late positive potential (LPP), an ERP that indexes attention allocation, we found that a valence-specific increase of the early portion of the LPP (eLPP, 250-500 ms) was associated with less emotional distraction in the sham group. Of note, stimulation with tDCS exerted an intensity related effect on this correlation. The later part of the LPP (lLPP, 500-1000 ms) was found to be correlated with reaction time, regardless of valence. General effect of tDCS on LPPs and task performance were not observed. These findings demonstrate that ERP recordings parallel to tDCS are feasible to investigate the neuronal underpinnings of stimulation effects on executive functions. Furthermore, they support the notion that the LPP induced by a distractive stimulus during a working memory task mirrors the additional allocation of neuronal resources with a specific sensitivity of the early LPP for highly arousing negative stimuli. Finally, together with the variable magnitude and direction of the emotional bias, the lack of systematic modulations of LPPs and behavior by tDCS further underlines the important influence of the individual brain activity patterns on stimulation effects both on the behavioral and neurophysiological level. PMID- 27378858 TI - Editorial: Glial Plasticity in Depression. PMID- 27378857 TI - Effects of Fluoxetine on Human Embryo Development. AB - The use of antidepressant treatment during pregnancy is increasing, and selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed antidepressants in pregnant women. Serotonin plays a role in embryogenesis, and serotonin transporters are expressed in two-cell mouse embryos. Thus, the aim of the present study was to evaluate whether fluoxetine, one of the most prescribed SSRI antidepressant world-wide, exposure influences the timing of different embryo developmental stages, and furthermore, to analyze what protein, and protein networks, are affected by fluoxetine in the early embryo development. Human embryos (n = 48) were randomly assigned to treatment with 0.25 or 0.5 MUM fluoxetine in culture medium. Embryo development was evaluated by time-lapse monitoring. The fluoxetine-induced human embryo proteome was analyzed by shotgun mass spectrometry. Protein secretion from fluoxetine-exposed human embryos was analyzed by use of high-multiplex immunoassay. The lower dose of fluoxetine had no influence on embryo development. A trend toward reduced time between thawing and start of cavitation was noted in embryos treated with 0.5 MUM fluoxetine (p = 0.065). Protein analysis by shotgun mass spectrometry detected 45 proteins that were uniquely expressed in fluoxetine-treated embryos. These proteins are involved in cell growth, survival, proliferation, and inflammatory response. Culturing with 0.5 MUM, but not 0.25 MUM fluoxetine, caused a significant increase in urokinase-type plasminogen activator (uPA) in the culture medium. In conclusion, fluoxetine has marginal effects on the timing of developmental stages in embryos, but induces expression and secretion of several proteins in a manner that depends on dose. For these reasons, and in line with current guidelines, the lowest possible dose of SSRI should be used in pregnant women who need to continue treatment. PMID- 27378859 TI - Mathematical Model of Evolution of Brain Parcellation. AB - We study the distribution of brain and cortical area sizes [parcellation units (PUs)] obtained for three species: mouse, macaque, and human. We find that the distribution of PU sizes is close to lognormal. We propose the mathematical model of evolution of brain parcellation based on iterative fragmentation and specialization. In this model, each existing PU has a probability to be split that depends on PU size only. This model suggests that the same evolutionary process may have led to brain parcellation in these three species. Within our model, region-to-region (macro) connectivity is given by the outer product form. We show that most experimental data on non-zero macaque cortex macroscopic-level connections can be explained by the outer product power-law form suggested by our model (62% for area V1). We propose a multiplicative Hebbian learning rule for the macroconnectome that could yield the correct scaling of connection strengths between areas. We thus propose an evolutionary model that may have contributed to both brain parcellation and mesoscopic level connectivity in mammals. PMID- 27378860 TI - Distinct Spatiotemporal Activation Patterns of the Perirhinal-Entorhinal Network in Response to Cortical and Amygdala Input. AB - The perirhinal (PER) and entorhinal cortex (EC) receive input from the agranular insular cortex (AiP) and the subcortical lateral amygdala (LA) and the main output area is the hippocampus. Information transfer through the PER/EC network however, is not always guaranteed. It is hypothesized that this network actively regulates the (sub)cortical activity transfer to the hippocampal network and that the inhibitory system is involved in this function. This study determined the recruitment by the AiP and LA afferents in PER/EC network with the use of voltage sensitive dye (VSD) imaging in horizontal mouse brain slices. Electrical stimulation (500 MUA) of the AiP induced activity that gradually propagated predominantly in the rostro-caudal direction: from the PER to the lateral EC (LEC). In the presence of 1 MUM of the competitive gamma-aminobutyric acid (GABAA) receptor antagonist bicuculline, AiP stimulation recruited the medial EC (MEC) as well. In contrast, LA stimulation (500 MUA) only induced activity in the deep layers of the PER. In the presence of bicuculline, the initial population activity in the PER propagated further towards the superficial layers and the EC after a delay. The latency of evoked responses decreased with increasing stimulus intensities (50-500 MUA) for both the AiP and LA stimuli. The stimulation threshold for evoking responses in the PER/EC network was higher for the LA than for the AiP. This study showed that the extent of the PER/EC network activation depends on release of inhibition. When GABAA dependent inhibition is reduced, both the AiP and the LA activate spatially overlapping regions, although in a distinct spatiotemporal fashion. It is therefore hypothesized that the inhibitory network regulates excitatory activity from both cortical and subcortical areas that has to be transmitted through the PER/EC network. PMID- 27378861 TI - Structural Plasticity, Effectual Connectivity, and Memory in Cortex. AB - Learning and memory is commonly attributed to the modification of synaptic strengths in neuronal networks. More recent experiments have also revealed a major role of structural plasticity including elimination and regeneration of synapses, growth and retraction of dendritic spines, and remodeling of axons and dendrites. Here we work out the idea that one likely function of structural plasticity is to increase "effectual connectivity" in order to improve the capacity of sparsely connected networks to store Hebbian cell assemblies that are supposed to represent memories. For this we define effectual connectivity as the fraction of synaptically linked neuron pairs within a cell assembly representing a memory. We show by theory and numerical simulation the close links between effectual connectivity and both information storage capacity of neural networks and effective connectivity as commonly employed in functional brain imaging and connectome analysis. Then, by applying our model to a recently proposed memory model, we can give improved estimates on the number of cell assemblies that can be stored in a cortical macrocolumn assuming realistic connectivity. Finally, we derive a simplified model of structural plasticity to enable large scale simulation of memory phenomena, and apply our model to link ongoing adult structural plasticity to recent behavioral data on the spacing effect of learning. PMID- 27378862 TI - Inhibition of Protease-Activated Receptor 1 Does not Affect Dendritic Homeostasis of Cultured Mouse Dentate Granule Cells. AB - Protease-activated receptors (PARs) are widely expressed in the central nervous system (CNS). While a firm link between PAR1-activation and functional synaptic and intrinsic neuronal properties exists, studies on the role of PAR1 in neural structural plasticity are scarce. The physiological function of PAR1 in the brain remains not well understood. We here sought to determine whether prolonged pharmacologic PAR1-inhibition affects dendritic morphologies of hippocampal neurons. To address this question we employed live-cell microscopy of mouse dentate granule cell dendrites in 3-week old entorhino-hippocampal slice cultures prepared from Thy1-GFP mice. A subset of cultures were treated with the PAR1 inhibitor SCH79797 (1 MUM; up to 3 weeks). No major effects of PAR1-inhibition on static and dynamic parameters of dentate granule cell dendrites were detected under control conditions. Granule cells of PAR1-deficient slice cultures showed unaltered dendritic morphologies, dendritic spine densities and excitatory synaptic strength. Furthermore, we report that PAR1-inhibition does not prevent dendritic retraction following partial deafferentation in vitro. Consistent with this finding, no major changes in PAR1-mRNA levels were detected in the denervated dentate gyrus (DG). We conclude that neural PAR1 is not involved in regulating the steady-state dynamics or deafferentation-induced adaptive changes of cultured dentate granule cell dendrites. These results indicate that drugs targeting neural PAR1-signals may not affect the stability and structural integrity of neuronal networks in healthy brain regions. PMID- 27378863 TI - Identification of Radial Glia Progenitors in the Developing and Adult Retina of Sharks. AB - Neural stem cells give rise to transient progenitors termed neuroepithelial cells (NECs) and radial glial cells (RGCs). RGCs represent the major source of neurons, glia and adult stem cells in several regions of the central nervous system (CNS). RGCs are mostly transient in mammals, but they are widely maintained in the adult CNS of fishes, where they continue to be morphologically similar to RGCs in the mammalian brain and fulfill similar roles as progenitors and guide for migrating neurons. The retina of fishes offers an exceptional model to approach the study of adult neurogenesis because of the presence of constitutive proliferation from the ciliary marginal zone (CMZ), containing NECs, and from adult glial cells with radial morphology (the Muller glia). However, the cellular hierarchies and precise contribution of different types of progenitors to adult neurogenesis remain unsolved. We have analyzed the transition from NECs to RGCs and RGC differentiation in the retina of the cartilaginous fish Scyliorhinus canicula, which offers a particularly good spatial and temporal frame to investigate this process. We have characterized progenitor and adult RGCs by immunohistochemical detection of glial markers as glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS). We have compared the emergence and localization of glial markers with that of proliferating cell nuclear antigen (PCNA, a proliferation maker) and Doublecortin (DCX, which increases at early stages of neuronal differentiation). During retinal development, GFAP-immunoreactive NECs located in the most peripheral CMZ (CMZp) codistribute with DCX-immunonegative cells. GFAP-immunoreactive RGCs and Muller cells are located in successive more central parts of the retina and codistribute with DCX- and DCX/GS-immunoreactive cells, respectively. The same types of progenitors are found in juveniles, suggesting that the contribution of the CMZ to adult neurogenesis implies a transition through the radial glia (RG) state. PMID- 27378864 TI - Ultra-High Field MRI Post Mortem Structural Connectivity of the Human Subthalamic Nucleus, Substantia Nigra, and Globus Pallidus. AB - INTRODUCTION: The subthalamic nucleus, substantia nigra, and globus pallidus, three nuclei of the human basal ganglia, play an important role in motor, associative, and limbic processing. The network of the basal ganglia is generally characterized by a direct, indirect, and hyperdirect pathway. This study aims to investigate the mesoscopic nature of these connections between the subthalamic nucleus, substantia nigra, and globus pallidus and their surrounding structures. METHODS: A human post mortem brain specimen including the substantia nigra, subthalamic nucleus, and globus pallidus was scanned on a 7 T MRI scanner. High resolution diffusion weighted images were used to reconstruct the fibers intersecting the substantia nigra, subthalamic nucleus, and globus pallidus. The course and density of these tracks was analyzed. RESULTS: Most of the commonly established projections of the subthalamic nucleus, substantia nigra, and globus pallidus were successfully reconstructed. However, some of the reconstructed fiber tracks such as the connections of the substantia nigra pars compacta to the other included nuclei and the connections with the anterior commissure have not been shown previously. In addition, the quantitative tractography approach showed a typical degree of connectivity previously not documented. An example is the relatively larger projections of the subthalamic nucleus to the substantia nigra pars reticulata when compared to the projections to the globus pallidus internus. DISCUSSION: This study shows that ultra-high field post mortem tractography allows for detailed 3D reconstruction of the projections of deep brain structures in humans. Although the results should be interpreted carefully, the newly identified connections contribute to our understanding of the basal ganglia. PMID- 27378865 TI - 512-Channel and 13-Region Simultaneous Recordings Coupled with Optogenetic Manipulation in Freely Behaving Mice. AB - The development of technologies capable of recording both single-unit activity and local field potentials (LFPs) over a wide range of brain circuits in freely behaving animals is the key to constructing brain activity maps. Although mice are the most popular mammalian genetic model, in vivo neural recording has been traditionally limited to smaller channel count and fewer brain structures because of the mouse's small size and thin skull. Here, we describe a 512-channel tetrode system that allows us to record simultaneously over a dozen cortical and subcortical structures in behaving mice. This new technique offers two major advantages - namely, the ultra-low cost and the do-it-yourself flexibility for targeting any combination of many brain areas. We show the successful recordings of both single units and LFPs from 13 distinct neural circuits of the mouse brain, including subregions of the anterior cingulate cortices, retrosplenial cortices, somatosensory cortices, secondary auditory cortex, hippocampal CA1, dentate gyrus, subiculum, lateral entorhinal cortex, perirhinal cortex, and prelimbic cortex. This 512-channel system can also be combined with Cre-lox neurogenetics and optogenetics to further examine interactions between genes, cell types, and circuit dynamics across a wide range of brain structures. Finally, we demonstrate that complex stimuli - such as an earthquake and fear inducing foot-shock - trigger firing changes in all of the 13 brain regions recorded, supporting the notion that neural code is highly distributed. In addition, we show that localized optogenetic manipulation in any given brain region could disrupt network oscillations and caused changes in single-unit firing patterns in a brain-wide manner, thereby raising the cautionary note of the interpretation of optogenetically manipulated behaviors. PMID- 27378866 TI - No Evidence for Automatic Remapping of Stimulus Features or Location Found with fMRI. AB - The input to our visual system shifts every time we move our eyes. To maintain a stable percept of the world, visual representations must be updated with each saccade. Near the time of a saccade, neurons in several visual areas become sensitive to the regions of visual space that their receptive fields occupy after the saccade. This process, known as remapping, transfers information from one set of neurons to another, and may provide a mechanism for visual stability. However, it is not clear whether remapping transfers information about stimulus features in addition to information about stimulus location. To investigate this issue, we recorded blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) responses while human subjects viewed images of faces and houses (two visual categories with many feature differences). Immediately after some image presentations, subjects made a saccade that moved the previously stimulated location to the opposite side of the visual field. We then used a combination of univariate analyses and multivariate pattern analyses to test whether information about stimulus location and stimulus features were remapped to the ipsilateral hemisphere after the saccades. We found no reliable indication of stimulus feature remapping in any region. However, we also found no reliable indication of stimulus location remapping, despite the fact that our paradigm was highly similar to previous fMRI studies of remapping. The absence of location remapping in our study precludes strong conclusions regarding feature remapping. However, these results also suggest that measurement of location remapping with fMRI depends strongly on the details of the experimental paradigm used. We highlight differences in our approach from the original fMRI studies of remapping, discuss potential reasons for the failure to generalize prior location remapping results, and suggest directions for future research. PMID- 27378867 TI - Non-anemic Iron Deficiency from Birth to Weaning Does Not Impair Growth or Memory in Piglets. AB - Early iron deficiency is associated with impaired (cognitive) development, the severity of which depends on the timing and duration of the under-supply of iron. To design effective treatment and prevention strategies for iron deficiency in humans, suited animal models are needed. In an earlier study (Antonides et al., 2015b) we separated 10 pairs of piglets from their mothers within a few days after birth and reared one sibling with artificial iron-deficient (ID) and the other with balanced control milk until weaning. ID piglets grew slower and showed poorer reference memory (RM) performance than their controls in a spatial holeboard task, even weeks after iron repletion. One putative intervening factor in that study was pre-weaning maternal deprivation. In an attempt to refine the piglet iron-deficiency model, we assessed whether piglets reared by sows, but withheld iron supplementation, can serve as animal model of iron deficiency. As sow milk is inherently ID, piglets normally receive a prophylactic iron injection. Ten pairs of piglets were housed with foster sows until weaning (4 weeks). One sibling per pair was randomly assigned to the control group (receiving iron dextran injections: 40 mg iron per kilogram body mass on days 3 and 10), the other to the ID group. From weaning, all pigs were fed a balanced commercial diet. Blood samples were taken in week 1, 3.5, 6, and 12. Pre-weaning blood iron values of ID piglets were lower than those of controls, but recovered to normal values after weaning. Hemoglobin of ID piglets did not reach anemic values. Hematocrit and hemoglobin of ID animals did not decrease, and serum iron even increased pre-weaning, suggesting that the piglets had access to an external source of iron, e.g., spilled feed or feces of the foster sows. Growth, and spatial memory assessed in the holeboard from 10 to 16 weeks of age, was unaffected in ID pigs. We conclude that sow-raised piglets are not a suitable model for iron-deficiency induced cognitive deficits in humans. Based on our previous and the present study, we conclude that growth and memory are only impaired in piglets that suffered from pre-weaning anemia. PMID- 27378869 TI - Editorial: Extinction Learning from a Mechanistic and Systems Perspective. PMID- 27378868 TI - Social Memory Formation Rapidly and Differentially Affects the Motivation and Performance of Vocal Communication Signals in the Bengalese Finch (Lonchura striata var. domestica). AB - Cognitive processes like the formation of social memories can shape the nature of social interactions between conspecifics. Male songbirds use vocal signals during courtship interactions with females, but the degree to which social memory and familiarity influences the likelihood and structure of male courtship song remains largely unknown. Using a habituation-dishabituation paradigm, we found that a single, brief (<30 s) exposure to a female led to the formation of a short term memory for that female: adult male Bengalese finches were significantly less likely to produce courtship song to an individual female when re-exposed to her 5 min later (i.e., habituation). Familiarity also rapidly decreased the duration of courtship songs but did not affect other measures of song performance (e.g., song tempo and the stereotypy of syllable structure and sequencing). Consistent with a contribution of social memory to the decrease in courtship song with repeated exposures to the same female, the likelihood that male Bengalese finches produced courtship song increased when they were exposed to a different female (i.e., dishabituation). Three consecutive exposures to individual females also led to the formation of a longer-term memory that persisted over days. Specifically, when courtship song production was assessed 2 days after initial exposures to females, males produced fewer and shorter courtship songs to familiar females than to unfamiliar females. Measures of song performance, however, were not different between courtship songs produced to familiar and unfamiliar females. The formation of a longer-term memory for individual females seemed to require at least three exposures because males did not differentially produce courtship song to unfamiliar females and females that they had been exposed to only once or twice. Taken together, these data indicate that brief exposures to individual females led to the rapid formation and persistence of social memories and support the existence of distinct mechanisms underlying the motivation to produce and the performance of courtship song. PMID- 27378871 TI - Editorial: Intellectual Disabilities in Down Syndrome from Birth and Throughout Life: Assessment and Treatment. PMID- 27378870 TI - Neural Dynamics of Emotional Salience Processing in Response to Voices during the Stages of Sleep. AB - Sleep has been related to emotional functioning. However, the extent to which emotional salience is processed during sleep is unknown. To address this concern, we investigated night sleep in healthy adults regarding brain reactivity to the emotionally (happily, fearfully) spoken meaningless syllables dada, along with correspondingly synthesized nonvocal sounds. Electroencephalogram (EEG) signals were continuously acquired during an entire night of sleep while we applied a passive auditory oddball paradigm. During all stages of sleep, mismatch negativity (MMN) in response to emotional syllables, which is an index for emotional salience processing of voices, was detected. In contrast, MMN to acoustically matching nonvocal sounds was undetected during Sleep Stage 2 and 3 as well as rapid eye movement (REM) sleep. Post-MMN positivity (PMP) was identified with larger amplitudes during Stage 3, and at earlier latencies during REM sleep, relative to wakefulness. These findings clearly demonstrated the neural dynamics of emotional salience processing during the stages of sleep. PMID- 27378872 TI - Dopamine Replacement Therapy, Learning and Reward Prediction in Parkinson's Disease: Implications for Rehabilitation. AB - The principal feature of Parkinson's disease (PD) is the impaired ability to acquire and express habitual-automatic actions due to the loss of dopamine in the dorsolateral striatum, the region of the basal ganglia associated with the control of habitual behavior. Dopamine replacement therapy (DRT) compensates for the lack of dopamine, representing the standard treatment for different motor symptoms of PD (such as rigidity, bradykinesia and resting tremor). On the other hand, rehabilitation treatments, exploiting the use of cognitive strategies, feedbacks and external cues, permit to "learn to bypass" the defective basal ganglia (using the dorsolateral area of the prefrontal cortex) allowing the patients to perform correct movements under executive-volitional control. Therefore, DRT and rehabilitation seem to be two complementary and synergistic approaches. Learning and reward are central in rehabilitation: both of these mechanisms are the basis for the success of any rehabilitative treatment. Anyway, it is known that "learning resources" and reward could be negatively influenced from dopaminergic drugs. Furthermore, DRT causes different well-known complications: among these, dyskinesias, motor fluctuations, and dopamine dysregulation syndrome (DDS) are intimately linked with the alteration in the learning and reward mechanisms and could impact seriously on the rehabilitative outcomes. These considerations highlight the need for careful titration of DRT to produce the desired improvement in motor symptoms while minimizing the associated detrimental effects. This is important in order to maximize the motor re-learning based on repetition, reward and practice during rehabilitation. In this scenario, we review the knowledge concerning the interactions between DRT, learning and reward, examine the most impactful DRT side effects and provide suggestions for optimizing rehabilitation in PD. PMID- 27378873 TI - Mifepristone Treatment during Early Adolescence Fails to Restore Maternal Deprivation-Induced Deficits in Behavioral Inhibition of Adult Male Rats. AB - Early life adversity has a profound impact on brain development and later life health. Animal models have provided insight how early life stress programs stress responsiveness and might contribute to the development of psychiatric disorders. In the present study, the long-term effects of maternal deprivation (MD) on behavioral inhibition and attention were examined in adult male Wistar rats. To this end animals were tested in the 5-choice serial reaction time task (5-choice SRTT). We also explored the potential of a 3-day treatment with the glucocorticoid receptor (GR) antagonist mifepristone during early adolescence to normalize putative behavioral effects of early life stress. Deprivation of the mother for 24 h on postnatal day (PND) 3 led to a modest but significant increase in premature responses in the 5-choice SRTT, but did not affect measures of attention. Body weight was lower in deprived animals from weaning until the start of testing. Early adolescent mifepristone treatment (PND 26-28) did not influence performance on the 5-choice SRTT and did not mitigate the deprivation-related impairment in behavioral inhibition. Our results indicate that MD leads to impaired behavioral inhibition, and that mifepristone treatment during early adolescence does not normalize the behavioral changes caused by early life stress. PMID- 27378874 TI - Subthalamic and Cortical Local Field Potentials Associated with Pilocarpine Induced Oral Tremor in the Rat. AB - Tremulous jaw movements (TJMs) are rapid vertical deflections of the lower jaw that resemble chewing but are not directed at any particular stimulus. In rodents, TJMs are induced by neurochemical conditions that parallel those seen in human Parkinsonism, including neurotoxic or pharmacological depletion of striatal dopamine (DA), DA antagonism, and cholinomimetic administration. Moreover, TJMs in rodents can be attenuated by antiparkinsonian agents, including levodopa (L DOPA), DA agonists, muscarinic antagonists, and adenosine A2A antagonists. In human Parkinsonian patients, exaggerated physiological synchrony is seen in the beta frequency band in various parts of the cortical/basal ganglia/thalamic circuitry, and activity in the tremor frequency range (3-7 Hz) also has been recorded. The present studies were undertaken to determine if tremor-related local field potential (LFP) activity could be recorded from motor cortex (M1) or subthalamic nucleus (STN) during the TJMs induced by the muscarinic agonist pilocarpine, which is a well-known tremorogenic agent. Pilocarpine induced a robust TJM response that was marked by rhythmic electromyographic (EMG) activity in the temporalis muscle. Compared to periods with no tremor activity, TJM epochs were characterized by increased LFP activity in the tremor frequency range in both neocortex and STN. Tremor activity was not associated with increased synchrony in the beta frequency band. These studies identified tremor-related LFP activity in parts of the cortical/basal ganglia circuitry that are involved in the pathophysiology of Parkinsonism. This research may ultimately lead to identification of the oscillatory neural mechanisms involved in the generation of tremulous activity, and promote development of novel treatments for tremor disorders. PMID- 27378875 TI - Mindfulness-Based Stress Reduction, Fear Conditioning, and The Uncinate Fasciculus: A Pilot Study. AB - Mindfulness has been suggested to impact emotional learning, but research on these processes is scarce. The classical fear conditioning/extinction/extinction retention paradigm is a well-known method for assessing emotional learning. The present study tested the impact of mindfulness training on fear conditioning and extinction memory and further investigated whether changes in white matter fiber tracts might support such changes. The uncinate fasciculus (UNC) was of particular interest in the context of emotional learning. In this pilot study, 46 healthy participants were quasi-randomized to a Mindfulness-Based Stress Reduction (MBSR, N = 23) or waitlist control (N = 23) group and underwent a two day fear conditioning, extinction learning, and extinction memory protocol before and after the course or control period. Skin conductance response (SCR) data served to measure the physiological response during conditioning and extinction memory phases. Diffusion tensor imaging (DTI) data were analyzed with probabilistic tractography and analyzed for changes of fractional anisotropy in the UNC. During conditioning, participants were able to maintain a differential response to conditioned vs. not conditioned stimuli following the MBSR course (i.e., higher sensitivity to the conditioned stimuli), while controls dropped the response. Extinction memory results were not interpretable due to baseline differences. MBSR participants showed a significant increase in fractional anisotropy in the UNC, while controls did not (group by time interaction missed significance). Pre-post changes in UNC were correlated with changes in the response to the conditioned stimuli. The findings suggest effects of mindfulness practice on the maintenance of sensitivity of emotional responses and suggest underlying neural plasticity. (ClinicalTrials.gov, Identifier NCT01320969, https://clinicaltrials.gov/ct2/show/NCT01320969). PMID- 27378876 TI - Behavioral Differences in the Upper and Lower Visual Hemifields in Shape and Motion Perception. AB - Perceptual accuracy is known to be influenced by stimuli location within the visual field. In particular, it seems to be enhanced in the lower visual hemifield (VH) for motion and space processing, and in the upper VH for object and face processing. The origins of such asymmetries are attributed to attentional biases across the visual field, and in the functional organization of the visual system. In this article, we tested content-dependent perceptual asymmetries in different regions of the visual field. Twenty-five healthy volunteers participated in this study. They performed three visual tests involving perception of shapes, orientation and motion, in the four quadrants of the visual field. The results of the visual tests showed that perceptual accuracy was better in the lower than in the upper visual field for motion perception, and better in the upper than in the lower visual field for shape perception. Orientation perception did not show any vertical bias. No difference was found when comparing right and left VHs. The functional organization of the visual system seems to indicate that the dorsal and the ventral visual streams, responsible for motion and shape perception, respectively, show a bias for the lower and upper VHs, respectively. Such a bias depends on the content of the visual information. PMID- 27378877 TI - Effects of Gene * Attachment Interaction on Adolescents' Emotion Regulation and Aggressive Hostile Behavior Towards their Mothers during a Computer Game. AB - Adolescence is a time of increased emotionality and major changes in emotion regulation often elicited in autonomy-relevant situations. Both genetic as well as social factors may lead to inter-individual differences in emotional processes in adolescence. We investigated whether both 5-HTTLPR and attachment security influence adolescents' observed emotionality, emotional dysregulation, and their aggressive hostile autonomy while interacting with their mothers. Eighty-eight adolescents at age 12 were observed in interaction with their mothers during a standardized, emotion eliciting computer game task. They were genotyped for the 5 HTTLPR, a repeat polymorphism in the promoter region of the serotonin transporter gene. Concurrent attachment quality was assessed by the Late Childhood Attachment Interview (LCAI). Results revealed a significant gene * attachment effect showing that ss/sl carriers of 5-HTTLPR show increased emotional dysregulation and aggressive hostile autonomy towards their mothers. The results of the study suggest that secure attachment in adolescence moderates the genetically based higher tendency for emotional dysregulation and aggressive reactions to restrictions of autonomy during emotional social interactions with their mothers. PMID- 27378878 TI - Ego-Dissolution and Psychedelics: Validation of the Ego-Dissolution Inventory (EDI). AB - AIMS: The experience of a compromised sense of "self", termed ego-dissolution, is a key feature of the psychedelic experience. This study aimed to validate the Ego Dissolution Inventory (EDI), a new 8-item self-report scale designed to measure ego-dissolution. Additionally, we aimed to investigate the specificity of the relationship between psychedelics and ego-dissolution. METHOD: Sixteen items relating to altered ego-consciousness were included in an internet questionnaire; eight relating to the experience of ego-dissolution (comprising the EDI), and eight relating to the antithetical experience of increased self-assuredness, termed ego-inflation. Items were rated using a visual analog scale. Participants answered the questionnaire for experiences with classical psychedelic drugs, cocaine and/or alcohol. They also answered the seven questions from the Mystical Experiences Questionnaire (MEQ) relating to the experience of unity with one's surroundings. RESULTS: Six hundred and ninety-one participants completed the questionnaire, providing data for 1828 drug experiences (1043 psychedelics, 377 cocaine, 408 alcohol). Exploratory factor analysis demonstrated that the eight EDI items loaded exclusively onto a single common factor, which was orthogonal to a second factor comprised of the items relating to ego-inflation (rho = -0.110), demonstrating discriminant validity. The EDI correlated strongly with the MEQ derived measure of unitive experience (rho = 0.735), demonstrating convergent validity. EDI internal consistency was excellent (Cronbach's alpha 0.93). Three analyses confirmed the specificity of ego-dissolution for experiences occasioned by psychedelic drugs. Firstly, EDI score correlated with drug-dose for psychedelic drugs (rho = 0.371), but not for cocaine (rho = 0.115) or alcohol (rho = -0.055). Secondly, the linear regression line relating the subjective intensity of the experience to ego-dissolution was significantly steeper for psychedelics (unstandardized regression coefficient = 0.701) compared with cocaine (0.135) or alcohol (0.144). Ego-inflation, by contrast, was specifically associated with cocaine experiences. Finally, a binary Support Vector Machine classifier identified experiences occasioned by psychedelic drugs vs. cocaine or alcohol with over 85% accuracy using ratings of ego-dissolution and ego-inflation alone. CONCLUSION: Our results demonstrate the psychometric structure, internal consistency and construct validity of the EDI. Moreover, we demonstrate the close relationship between ego-dissolution and the psychedelic experience. The EDI will facilitate the study of the neuronal correlates of ego-dissolution, which is relevant for psychedelic-assisted psychotherapy and our understanding of psychosis. PMID- 27378879 TI - Proprioception Is Necessary for Body Schema Plasticity: Evidence from a Deafferented Patient. AB - The ability of using a large variety of tools is important in our daily life. Behind human tool-use abilities lays the brain capacity to incorporate tools into the body representation for action (Body Schema, BS), thought to rely mainly on proprioceptive information. Here, we tested whether tool incorporation is possible in absence of proprioception by studying a patient with right upper-limb deafferentation. We adopted a paradigm sensitive to changes of the BS and analyzed the kinematics of free-hand movements before and after tool-use, in three sessions over a period of 2 years. In the first session, before tool-use, the kinematics of the deafferented hand was disrupted. Similarly, the first movements with the tool (a mechanical grabber elongating the arm by ~40 cm) showed an abnormal profile that tended to normalize at the end of the session. Subsequent free-hand movements were also normalized. At session 2, 6 months later, the patient exhibited normal free-hand kinematic profiles, additionally showing changes in grasping kinematics after tool-use, but no sign of tool incorporation. A follow-up 2 years later, further confirmed the normalized kinematic profile but the absence of tool incorporation. This first description of tool-use in absence of proprioception shows the fundamental role of proprioception in the update of the BS. These results provide an important further step in understanding human motor control and have implications for future development of rehabilitation programs for patients with sensory deficits. PMID- 27378880 TI - Characterization of Face-Selective Patches in Orbitofrontal Cortex. AB - Face processing involves a complex, multimodal brain network. While visual perceptual face patches in posterior parts of the brain have been studied for over a decade, the existence and properties of face-selective regions in orbitofrontal cortex (OFC) is a relatively new area of research. While regions of OFC are implicated in the emotional processing of faces, this is typically interpreted as a domain-general response to affective value rather than a face- or socially-specific response. However, electrophysiology studies in monkeys have identified neurons in OFC that respond more to faces than any other stimuli. Here, we characterize the prevalence and location of OFC face-selective regions in 20 healthy college students. We did this by including another biologically motivating category (appetizing foods) in a variant of the standard face localizer. Results show that face-selective patches can be identified at the individual level. Furthermore, in both a region of interest (ROI) and a whole brain analysis, medial regions of the OFC were face-selective, while lateral regions were responsive to faces and foods, indicating a domain-general response in lateral OFC. Medial OFC (mOFC) response to faces scales in relationship to a measure of social motivation that is distinct from face processing abilities associated with fusiform cortex. PMID- 27378881 TI - A Mathematical Model of Levodopa Medication Effect on Basal Ganglia in Parkinson's Disease: An Application to the Alternate Finger Tapping Task. AB - Malfunctions in the neural circuitry of the basal ganglia (BG), induced by alterations in the dopaminergic system, are responsible for an array of motor disorders and milder cognitive issues in Parkinson's disease (PD). Recently Baston and Ursino (2015a) presented a new neuroscience mathematical model aimed at exploring the role of basal ganglia in action selection. The model is biologically inspired and reproduces the main BG structures and pathways, modeling explicitly both the dopaminergic and the cholinergic system. The present work aims at interfacing this neurocomputational model with a compartmental model of levodopa, to propose a general model of medicated Parkinson's disease. Levodopa effect on the striatum was simulated with a two-compartment model of pharmacokinetics in plasma joined with a motor effect compartment. The latter is characterized by the levodopa removal rate and by a sigmoidal relationship (Hill law) between concentration and effect. The main parameters of this relationship are saturation, steepness, and the half-maximum concentration. The effect of levodopa is then summed to a term representing the endogenous dopamine effect, and is used as an external input for the neurocomputation model; this allows both the temporal aspects of medication and the individual patient characteristics to be simulated. The frequency of alternate tapping is then used as the outcome of the whole model, to simulate effective clinical scores. Pharmacokinetic pharmacodynamic modeling was preliminary performed on data of six patients with Parkinson's disease (both "stable" and "wearing-off" responders) after levodopa standardized oral dosing over 4 h. Results show that the model is able to reproduce the temporal profiles of levodopa in plasma and the finger tapping frequency in all patients, discriminating between different patterns of levodopa motor response. The more influential parameters are the Hill coefficient, related with the slope of the effect sigmoidal relationship, the drug concentration at half-maximum effect, and the drug removal rate from the effect compartment. The model can be of value to gain a deeper understanding on the pharmacokinetics and pharmacodynamics of the medication, and on the way dopamine is exploited in the neural circuitry of the basal ganglia in patients at different stages of the disease progression. PMID- 27378882 TI - Differing Connectivity of Exner's Area for Numbers and Letters. AB - There is a growing body of evidence indicating a crucial role of Exner's area in (hand-) writing symbolic codes such as letters and words. However, a recent study reported a patient with a lesion affecting Broca's and Exner's area, who suffered from severe peripheral agraphia for letters but not for Arabic digits. The authors suggested a speculative account postulating differential connectivity of Exner's area for numbers and letters in order to explain this dissociation. In the present study, we evaluated this account, employing atlas-based tractography for the patient's anatomy, deterministic fiber-tracking as well as an automated toolkit to investigate the connectivity of Exner's area in healthy adults. In particular, fiber pathways connecting Exner's area with areas associated with language processing (e.g., the arcuate fascicle, ventral pathways encompassing the external/extreme capsule system) reached the inferior part of Exner's area, while fronto-parietal fibers (e.g., the superior longitudinal fascicle) connected the upper part of Exner's area with the intraparietal sulcus typically involved in number processing. Our results substantiated the differential connectivity account for Exner's area by identifying the neural connections between fiber tracts and cortex areas of interest. Our data strongly suggest that white matter connectivity should be taken into account when investigating the neural underpinnings of impaired and intact human cognition. PMID- 27378883 TI - Doubt in the Insula: Risk Processing in Obsessive-Compulsive Disorder. AB - Extensive cleaning or checking of patients with obsessive-compulsive disorder (OCD) are often interpreted as strategies to avoid harm and as an expression of the widespread belief that OCD patients are more risk-averse. However, despite its clinical significance, the neural basis of risk attitude in OCD is unknown. Here, we investigated neural activity during risk processing using functional magnetic resonance imaging and simultaneously assessed risk attitude using a separate behavioral paradigm in OCD patients with different symptoms versus healthy controls (HCs). We found opposite insula responses to high versus low risk in OCD patients compared to HCs: a positive correlation between insula activity and risk-aversion in patients versus a negative correlation in controls. Although OCD patients overall were not more risk-averse than controls, there were differences between subgroups of OCD patients: patients with doubt/checking symptoms were more risk-averse than other patients. Taken together, OCD patients show a reversed pattern of risk processing by the insula compared to HCs. Moreover, the data suggest that increased activation of the insula signals an abnormal urge to avoid risks in the subpopulation of OCD patients with doubt and checking symptoms. These results indicate a role for the insula in excessive risk avoidance relevant to OCD. PMID- 27378885 TI - Oscillation Phase Locking and Late ERP Components of Intracranial Hippocampal Recordings Correlate to Patient Performance in a Working Memory Task. AB - In working memory tasks, stimulus presentation induces a resetting of intracranial temporal lobe oscillations in multiple frequency bands. To further understand the functional relevance of this phenomenon, we investigated whether working memory performance depends on the phase precision of ongoing oscillations in the hippocampus. We recorded intra-hippocampal local field potentials in individuals performing a working memory task. Two types of trials were administered. For high memory trials presentation of a list of four letters ("List") was followed by a single letter memory probe ("Test"). Low memory load trials, consisting of four identical letters (AAAA) followed by a probe with the same letter (A), were interspersed. Significant phase locking of ongoing oscillations across trials, estimated by the Pairwise Phase Consistency Index (PPCI) was observed in delta (0.5-4 Hz), theta (5-7 Hz), and alpha (8-12 Hz) bands during stimulus presentation and recall but was increased in low memory load trials. Across patients however, higher delta PPCIs during recall in the left hippocampus were associated with faster reaction times. Because phase locking could also be interpreted as a consequence of a stimulus evoked potential, we performed event related potential analysis (ERP) and examined the relationship of ERP components with performance. We found that both amplitude and latency of late ERP components correlated with both reaction time and accuracy. We propose that, in the Sternberg task, phase locking of oscillations, or alternatively its ERP correlate, synchronizes networks within the hippocampus and connected structures that are involved in working memory. PMID- 27378884 TI - Sex Differences in the Neural Correlates of Specific and General Autobiographical Memory. AB - Autobiographical memory (AM) underlies the formation and temporal continuity over time of personal identity. The few studies on sex-related differences in AM suggest that men and women adopt different cognitive or emotional strategies when retrieving AMs. However, none of the previous works has taken into account the distinction between episodic autobiographical memory (EAM), consisting in the retrieval of specific events by means of mental time travel, and semantic autobiographical memory (SAM), which stores general personal events. Thus, it remains unclear whether differences in these strategies depend on the nature of the memory content to be retrieved. In the present study we employed functional MRI to examine brain activity underlying potential sex differences in EAM and SAM retrieval focusing on the differences in strategies related to the emotional aspects of memories while controlling for basic cognitive strategies. On the behavioral level, there was no significant sex difference in memory performances or subjective feature ratings of either type of AM. Activations common to men and women during AM retrieval were observed in a typical bilateral network comprising medial and lateral temporal regions, precuneus, occipital cortex as well as prefrontal cortex. Contrast analyses revealed that there was no difference between men and women in the EAM condition. In the SAM condition, women showed an increased activity, compared to men, in the dorsal anterior cingulate cortex, inferior parietal and precentral gyrus. Overall, these findings suggest that differential neural activations reflect sex-specific strategies related to emotional aspects of AMs, particularly regarding SAM. We propose that this pattern of activation during SAM retrieval reflects the cognitive cost linked to emotion regulation strategies recruited by women compared to men. These sex related differences have interesting implications for understanding psychiatric disorders with differential sex prevalence and in which one of key features is overgenerality in AM. PMID- 27378886 TI - Changes in Balance Strategy and Neuromuscular Control during a Fatiguing Balance Task-A Study in Perturbed Unilateral Stance. AB - Fatigue impairs sensorimotor performance, reduces spinal reflexes and affects the interaction of antagonistic muscles in complex motor tasks. Although there is literature dealing with the interference of fatigue and postural control, the interpretation is confounded by the variety of paradigms used to study it. This study aimed to evaluate the effects of postural fatigue on balance control and strategy, as well as on neuromuscular modulation, in response to postural perturbation (PERT) during a fatiguing balance task. A fatigue protocol consisting of continuous exposure to perturbations until exhaustion was executed in 24 subjects. Number of failed attempts, paths of center of pressure displacement (COP), ankle, knee, and hip joint kinematics, electromyographic activity of the soleus (SOL), tibialis anterior (TA), rectus femoris (RF), vastus lateralis (VL), biceps femoris (BF), and gluteus maximus muscles (GM) and spinal excitability of SOL at the peak of the short-latency responses (SLR) were recorded after posterior PERT. The co-contraction index (CCI) was calculated for TA_SOL, VL_BF and RF_GM. (1) The number of failed attempts significantly increased while COP amplitude and velocity, as well as angular excursion at the ankle, knee and hip joints, decreased with fatigue (P < 0.05). (2) Concomitantly, CCI of SOL_TA, VL_BF and RF_GM increased and spinal excitability in SOL declined. (3) Adaptations progressively augmented with progressing exhaustion and occurred in the distal prior to proximal segment. Distinctly deteriorated balance ability was accompanied by a modified neuromuscular control-the increase in co contraction reflected by simultaneously activated antagonists is accompanied by smaller knee and hip joint excursions, indicating an elevated level of articular stiffness. These changes may be associated with an exaggerated postural rigidity and could have caused the delayed and reduced postural reactions that are reflected in the changes in COP displacement when compensating for sudden PERT. The reduction in spinal excitability may either be caused by fatigue itself or by an increase in reciprocal inhibition due to augmented TA activity. PMID- 27378887 TI - An Exploration of Rhythmic Grouping of Speech Sequences by French- and German Learning Infants. AB - Rhythm in music and speech can be characterized by a constellation of several acoustic cues. Individually, these cues have different effects on rhythmic perception: sequences of sounds alternating in duration are perceived as short long pairs (weak-strong/iambic pattern), whereas sequences of sounds alternating in intensity or pitch are perceived as loud-soft, or high-low pairs (strong weak/trochaic pattern). This perceptual bias-called the Iambic-Trochaic Law (ITL) has been claimed to be an universal property of the auditory system applying in both the music and the language domains. Recent studies have shown that language experience can modulate the effects of the ITL on rhythmic perception of both speech and non-speech sequences in adults, and of non-speech sequences in 7.5 month-old infants. The goal of the present study was to explore whether language experience also modulates infants' grouping of speech. To do so, we presented sequences of syllables to monolingual French- and German-learning 7.5-month-olds. Using the Headturn Preference Procedure (HPP), we examined whether they were able to perceive a rhythmic structure in sequences of syllables that alternated in duration, pitch, or intensity. Our findings show that both French- and German learning infants perceived a rhythmic structure when it was cued by duration or pitch but not intensity. Our findings also show differences in how these infants use duration and pitch cues to group syllable sequences, suggesting that pitch cues were the easier ones to use. Moreover, performance did not differ across languages, failing to reveal early language effects on rhythmic perception. These results contribute to our understanding of the origin of rhythmic perception and perceptual mechanisms shared across music and speech, which may bootstrap language acquisition. PMID- 27378888 TI - Intermittent Theta Burst Stimulation Increases Reward Responsiveness in Individuals with Higher Hedonic Capacity. AB - BACKGROUND: Repetitive transcranial magnetic stimulation over the left dorsolateral prefrontal cortex (DLPFC) has been documented to influence striatal and orbitofrontal dopaminergic activity implicated in reward processing. However, the exact neuropsychological mechanisms of how DLPFC stimulation may affect the reward system and how trait hedonic capacity may interact with the effects remains to be elucidated. OBJECTIVE: In this sham-controlled study in healthy individuals, we investigated the effects of a single session of neuronavigated intermittent theta burst stimulation (iTBS) on reward responsiveness, as well as the influence of trait hedonic capacity. METHODS: We used a randomized crossover single session iTBS design with an interval of 1 week. We assessed reward responsiveness using a rewarded probabilistic learning task and measured individual trait hedonic capacity (the ability to experience pleasure) with the temporal experience of pleasure scale questionnaire. RESULTS: As expected, the participants developed a response bias toward the most rewarded stimulus (rich stimulus). Reaction time and accuracy for the rich stimulus were respectively shorter and higher as compared to the less rewarded stimulus (lean stimulus). Active or sham stimulation did not seem to influence the outcome. However, when taking into account individual trait hedonic capacity, we found an early significant increase in the response bias only after active iTBS. The higher the individual's trait hedonic capacity, the more the response bias toward the rich stimulus increased after the active stimulation. CONCLUSION: When taking into account trait hedonic capacity, one active iTBS session over the left DLPFC improved reward responsiveness in healthy male participants with higher hedonic capacity. This suggests that individual differences in hedonic capacity may influence the effects of iTBS on the reward system. PMID- 27378889 TI - The Dorsal Rather than Ventral Pathway Better Reflects Individual Syntactic Abilities in Second Language. AB - The left inferior frontal gyrus (IFG) has been reported to be critically involved in syntactic processing, not only in first language (L1), but in second language (L2). Indeed, the leftward lateralization of the IFG has been shown to be correlated with the performance of a syntactic task in L2. Given that posterior language-related regions are systematically connected with the left IFG, the next question is which of the dorsal and ventral pathways is more critical to the individual syntactic abilities in L2. Here we used diffusion magnetic resonance imaging (MRI) and tractography with newly developed semi-automatic methods of defining seeds and selecting regions of interest (ROIs). We calculated mean thickness and fractional anisotropy (FA) in each ROI for the arcuate fasciculus (Arcuate) of the dorsal pathway, as well as for the inferior fronto-occipital fasciculus (IFOF) of the ventral pathway. In Experiment I, we performed partial correlation analyses between FA and the accuracy of the syntactic task, removing the effects of the accuracy of a spelling task, gender, and handedness. Among the two pathways in each hemisphere, only FA of the left Arcuate was significantly correlated with individual accuracy of the syntactic task. In Experiment II, we recruited monozygotic twins and examined to what extent their L2 abilities and their structural properties were similar. Within twin pairs, the highest significant correlation was observed for reaction times of the spelling task, while the correlation for the accuracy of the syntactic task was marginal; these two correlation coefficients were significantly different. Moreover, the thickness of the left Arcuate was highly correlated within pairs, while its FA, as well as the thickness/FA in the ventral pathways, was not significantly correlated. The correlation coefficient for the thickness of the left Arcuate was significantly larger than that of the left IFOF. These results suggest that the thickness of the left Arcuate is more associated with the shared genetic/environmental factors, whereas both of mutually correlated FA in the left Arcuate and individual syntactic abilities in L2 may be less prone to these shared factors. PMID- 27378890 TI - Comparing the Neural Correlates of Conscious and Unconscious Conflict Control in a Masked Stroop Priming Task. AB - Although previous studies have suggested that conflict control can occur in the absence of consciousness, the brain mechanisms underlying unconscious and conscious conflict control remain unclear. The current study used a rapid event related functional magnetic resonance imaging design to collect data from 24 participants while they performed a masked Stroop priming task under both conscious and unconscious conditions. The results revealed that the fronto parietal conflict network, including medial frontal cortex (MFC), left and right dorsal lateral prefrontal cortex (DLPFC), and posterior parietal cortex (PPC), was activated by both conscious and unconscious Stroop priming, even though in MFC and left DLPFC the activations elicited by unconscious Stroop priming were smaller than conscious Stroop priming. The findings provide evidence for the existence of quantitative differences between the neural substrates of conscious and unconscious conflict control. PMID- 27378891 TI - The Cognitive Side of M1. AB - The primary motor cortex (M1) is traditionally implicated in voluntary movement control. In order to test the hypothesis that there is a functional topography of M1 activation in studies where it has been implicated in higher cognitive tasks we performed activation-likelihood-estimation (ALE) meta-analyses of functional neuroimaging experiments reporting M1 activation in relation to six cognitive functional categories for which there was a sufficient number of studies to include, namely motor imagery, working memory, mental rotation, social/emotion/empathy, language, and auditory processing. The six categories activated different sub-sectors of M1, either bilaterally or lateralized to one hemisphere. Notably, the activations found in the M1 of the left or right hemisphere detected in our study were unlikely due to button presses. In fact, all contrasts were selected in order to eliminate M1 activation due to activity related to the finger button press. In addition, we identified the M1 sub-region of Area 4a commonly activated by 4/6 categories, namely motor imagery and working memory, emotion/empathy, and language. Overall, our findings lend support to the idea that there is a functional topography of M1 activation in studies where it has been found activated in higher cognitive tasks and that the left Area 4a can be involved in a number of cognitive processes, likely as a product of implicit mental simulation processing. PMID- 27378892 TI - The Do's and Don'ts of Neurofeedback Training: A Review of the Controlled Studies Using Healthy Adults. AB - The goal of EEG neurofeedback (EEG-NFB) training is to induce changes in the power of targeted EEG bands to produce beneficial changes in cognitive or motor function. The effectiveness of different EEG-NFB protocols can be measured using two dependent variables: (1) changes in EEG activity and (2) behavioral changes of a targeted function (for therapeutic applications the desired changes should be long-lasting). To firmly establish a causal link between these variables and the selected protocol, similar changes should not be observed when appropriate control paradigms are used. The main objective of this review is to evaluate the evidence, reported in the scientific literature, which supports the validity of various EEG-NFB protocols. Our primary concern is to highlight the role that uncontrolled nonspecific factors can play in the results generated from EEG-NFB studies. Nonspecific factors are often ignored in EEG-NFB designs or the data are not presented, which means conclusions should be interpreted cautiously. As an outcome of this review we present a do's and don'ts list, which can be used to develop future EEG-NFB methodologies, based on the small set of experiments in which the proper control groups have excluded non-EEG-NFB related effects. We found two features which positively correlated with the expected changes in power of the trained EEG band(s): (1) protocols which focused on training a smaller number of frequency bands and (2) a bigger number of electrodes used for neurofeedback training. However, we did not find evidence in support of the positive relationship between power changes of a trained frequency band(s) and specific behavioral effects. PMID- 27378894 TI - Mid-Task Break Improves Global Integration of Functional Connectivity in Lower Alpha Band. AB - Numerous efforts have been devoted to revealing neurophysiological mechanisms of mental fatigue, aiming to find an effective way to reduce the undesirable fatigue related outcomes. Until recently, mental fatigue is thought to be related to functional dysconnectivity among brain regions. However, the topological representation of brain functional connectivity altered by mental fatigue is only beginning to be revealed. In the current study, we applied a graph theoretical approach to analyse such topological alterations in the lower alpha band (8~10 Hz) of EEG data from 20 subjects undergoing a two-session experiment, in which one session includes four successive blocks with visual oddball tasks (session 1) whereas a mid-task break was introduced in the middle of four task blocks in the other session (session 2). Phase lag index (PLI) was then employed to measure functional connectivity strengths for all pairs of EEG channels. Behavior and connectivity maps were compared between the first and last task blocks in both sessions. Inverse efficiency scores (IES = reaction time/response accuracy) were significantly increased in the last task block, showing a clear effect of time-on task in participants. Furthermore, a significant block-by-session interaction was revealed in the IES, suggesting the effectiveness of the mid-task break on maintaining task performance. More importantly, a significant session-independent deficit of global integration and an increase of local segregation were found in the last task block across both sessions, providing further support for the presence of a reshaped topology in functional brain connectivity networks under fatigue state. Moreover, a significant block-by-session interaction was revealed in the characteristic path length, small-worldness, and global efficiency, attributing to the significantly disrupted network topology in session 1 in comparison of the maintained network structure in session 2. Specifically, we found increased nodal betweenness centrality in several channels resided in frontal regions in session 1, resembling the observations of more segregated global architecture under fatigue state. Taken together, our findings provide insights into the substrates of brain functional dysconnectivity patterns for mental fatigue and reiterate the effectiveness of the mid-task break on maintaining brain network efficiency. PMID- 27378893 TI - Implicit Timing as the Missing Link between Neurobiological and Self Disorders in Schizophrenia? AB - Disorders of consciousness and the self are at the forefront of schizophrenia symptomatology. Patients are impaired in feeling themselves as the authors of their thoughts and actions. In addition, their flow of consciousness is disrupted, and thought fragmentation has been suggested to be involved in the patients' difficulties in feeling as being one unique, unchanging self across time. Both impairments are related to self disorders, and both have been investigated at the experimental level. Here we review evidence that both mechanisms of motor control and the temporal structure of signal processing are impaired in schizophrenia patients. Based on this review, we propose that the sequencing of action and perception plays a key role in the patients' impairments. Furthermore, the millisecond time scale of the disorders, as well as the impaired sequencing, highlights the cooperation between brain networks including the cerebellum, as proposed by Andreasen (1999). We examine this possibility in the light of recent knowledge on the anatomical and physiological properties of the cerebellum, its role in timing, and its involvement in known physiological impairments in patients with schizophrenia, e.g., resting states and brain dynamics. A disruption in communication between networks involving the cerebellum, related to known impairments in dopamine, glutamate and GABA transmission, may help to better explain why patients experience reduced attunement with the external world and possibly with themselves. PMID- 27378895 TI - Bodily Experience in Schizophrenia: Factors Underlying a Disturbed Sense of Body Ownership. AB - Emerging evidence is now challenging the view that patients diagnosed with schizophrenia experience a selective deficit in their sense of agency. Additional disturbances seem to exist in their sense of body ownership. However, the factors underlying this disturbance in body ownership remain elusive. Knowledge of these factors, and increased understanding of how body ownership is related to other abnormalities seen in schizophrenia, could ultimately advance development of new treatments. Research on body ownership in schizophrenia has mainly been investigated with the rubber hand illusion (RHI). Schizophrenia patients show higher susceptibility to the RHI, which may be explained by a stronger reliance on multisensory information over weaker stored body representations. This review shows that a coherent sense of body ownership arises from the integration of both bottom-up sensory processes and higher order, top-down bodily- and perceptual representations. Multisensory integration, temporal binding, anticipation, intention and efferent signals all partly modulate the complex experience of body ownership. Specifically, we propose that patients with schizophrenia have weaker stored body representations, and rely to a greater extent on external stimuli, such as visual information, due to imprecise or highly variable internal predictions. Moreover, the reduced sense of agency in schizophrenia may additionally contribute to the disturbed sense of body ownership, as evidence from healthy participants suggests that agency and body ownership are interrelated. Vice versa, a reduced sense of body ownership may also contribute to a reduced sense of agency. Future studies should explicitly target the precise relationship between the two in schizophrenia. PMID- 27378897 TI - Bumps in Small-World Networks. AB - We consider a network of coupled excitatory and inhibitory theta neurons which is capable of supporting stable spatially-localized "bump" solutions. We randomly add long-range and simultaneously remove short-range connections within the network to form a small-world network and investigate the effects of this rewiring on the existence and stability of the bump solution. We consider two limits in which continuum equations can be derived; bump solutions are fixed points of these equations. We can thus use standard numerical bifurcation analysis to determine the stability of these bumps and to follow them as parameters (such as rewiring probabilities) are varied. We find that under some rewiring schemes bumps are quite robust, whereas in other schemes they can become unstable via Hopf bifurcation or even be destroyed in saddle-node bifurcations. PMID- 27378896 TI - Alien Hand, Restless Brain: Salience Network and Interhemispheric Connectivity Disruption Parallel Emergence and Extinction of Diagonistic Dyspraxia. AB - Diagonistic dyspraxia (DD) is by far the most spectacular manifestation reported by sufferers of acute corpus callosum (CC) injury (so-called "split-brain"). In this form of alien hand syndrome, one hand acts at cross purposes with the other "against the patient's will". Although recent models view DD as a disorder of motor control, there is still little information regarding its neural underpinnings, due to widespread connectivity changes produced by CC insult, and the obstacle that non-volitional movements represent for task-based functional neuroimaging studies. Here, we studied patient AM, the first report of DD in patient with complete developmental CC agenesis. This unique case also offers the opportunity to study the resting-state connectomics of DD in the absence of diffuse changes subsequent to CC injury or surgery. AM developed DD following status epilepticus (SE) which resolved over a 2-year period. Whole brain functional connectivity (FC) was compared (Crawford-Howell [CH]) to 16 controls during the period of acute DD symptoms (Time 1) and after remission (Time 2). Whole brain graph theoretical models were also constructed and topological efficiency examined. At Time 1, disrupted FC was observed in inter-hemispheric and intra-hemispheric right edges, involving frontal superior and midline structures. Graph analysis indicated disruption of the efficiency of salience and right frontoparietal (FP) networks. At Time 2, after remission of diagnostic dyspraxia symptoms, FC and salience network changes had resolved. In sum, longitudinal analysis of connectivity in AM indicates that DD behaviors could result from disruption of systems that support the experience and control of volitional movements and the ability to generate appropriate behavioral responses to salient stimuli. This also raises the possibility that changes to large-scale functional architecture revealed by resting-state functional magnetic resonance imaging (fMRI) (rs-fMRI) may provide relevant information on the evolution of behavioral syndromes in addition to that provided by structural and task-based functional imaging. PMID- 27378899 TI - Scene Construction, Visual Foraging, and Active Inference. AB - This paper describes an active inference scheme for visual searches and the perceptual synthesis entailed by scene construction. Active inference assumes that perception and action minimize variational free energy, where actions are selected to minimize the free energy expected in the future. This assumption generalizes risk-sensitive control and expected utility theory to include epistemic value; namely, the value (or salience) of information inherent in resolving uncertainty about the causes of ambiguous cues or outcomes. Here, we apply active inference to saccadic searches of a visual scene. We consider the (difficult) problem of categorizing a scene, based on the spatial relationship among visual objects where, crucially, visual cues are sampled myopically through a sequence of saccadic eye movements. This means that evidence for competing hypotheses about the scene has to be accumulated sequentially, calling upon both prediction (planning) and postdiction (memory). Our aim is to highlight some simple but fundamental aspects of the requisite functional anatomy; namely, the link between approximate Bayesian inference under mean field assumptions and functional segregation in the visual cortex. This link rests upon the (neurobiologically plausible) process theory that accompanies the normative formulation of active inference for Markov decision processes. In future work, we hope to use this scheme to model empirical saccadic searches and identify the prior beliefs that underwrite intersubject variability in the way people forage for information in visual scenes (e.g., in schizophrenia). PMID- 27378898 TI - A System Computational Model of Implicit Emotional Learning. AB - Nowadays, the experimental study of emotional learning is commonly based on classical conditioning paradigms and models, which have been thoroughly investigated in the last century. Unluckily, models based on classical conditioning are unable to explain or predict important psychophysiological phenomena, such as the failure of the extinction of emotional responses in certain circumstances (for instance, those observed in evaluative conditioning, in post-traumatic stress disorders and in panic attacks). In this manuscript, starting from the experimental results available from the literature, a computational model of implicit emotional learning based both on prediction errors computation and on statistical inference is developed. The model quantitatively predicts (a) the occurrence of evaluative conditioning, (b) the dynamics and the resistance-to-extinction of the traumatic emotional responses, (c) the mathematical relation between classical conditioning and unconditioned stimulus revaluation. Moreover, we discuss how the derived computational model can lead to the development of new animal models for resistant-to-extinction emotional reactions and novel methodologies of emotions modulation. PMID- 27378900 TI - A Neuronal Network Model for Pitch Selectivity and Representation. AB - Pitch is a perceptual correlate of periodicity. Sounds with distinct spectra can elicit the same pitch. Despite the importance of pitch perception, understanding the cellular mechanism of pitch perception is still a major challenge and a mechanistic model of pitch is lacking. A multi-stage neuronal network model is developed for pitch frequency estimation using biophysically-based, high resolution coincidence detector neurons. The neuronal units respond only to highly coincident input among convergent auditory nerve fibers across frequency channels. Their selectivity for only very fast rising slopes of convergent input enables these slope-detectors to distinguish the most prominent coincidences in multi-peaked input time courses. Pitch can then be estimated from the first-order interspike intervals of the slope-detectors. The regular firing pattern of the slope-detector neurons are similar for sounds sharing the same pitch despite the distinct timbres. The decoded pitch strengths also correlate well with the salience of pitch perception as reported by human listeners. Therefore, our model can serve as a neural representation for pitch. Our model performs successfully in estimating the pitch of missing fundamental complexes and reproducing the pitch variation with respect to the frequency shift of inharmonic complexes. It also accounts for the phase sensitivity of pitch perception in the cases of Schroeder phase, alternating phase and random phase relationships. Moreover, our model can also be applied to stochastic sound stimuli, iterated-ripple-noise, and account for their multiple pitch perceptions. PMID- 27378901 TI - A Nonlinear Causality Estimator Based on Non-Parametric Multiplicative Regression. AB - Causal prediction has become a popular tool for neuroscience applications, as it allows the study of relationships between different brain areas during rest, cognitive tasks or brain disorders. We propose a nonparametric approach for the estimation of nonlinear causal prediction for multivariate time series. In the proposed estimator, C NPMR , Autoregressive modeling is replaced by Nonparametric Multiplicative Regression (NPMR). NPMR quantifies interactions between a response variable (effect) and a set of predictor variables (cause); here, we modified NPMR for model prediction. We also demonstrate how a particular measure, the sensitivity Q, could be used to reveal the structure of the underlying causal relationships. We apply C NPMR on artificial data with known ground truth (5 datasets), as well as physiological data (2 datasets). C NPMR correctly identifies both linear and nonlinear causal connections that are present in the artificial data, as well as physiologically relevant connectivity in the real data, and does not seem to be affected by filtering. The Sensitivity measure also provides useful information about the latent connectivity.The proposed estimator addresses many of the limitations of linear Granger causality and other nonlinear causality estimators. C NPMR is compared with pairwise and conditional Granger causality (linear) and Kernel-Granger causality (nonlinear). The proposed estimator can be applied to pairwise or multivariate estimations without any modifications to the main method. Its nonpametric nature, its ability to capture nonlinear relationships and its robustness to filtering make it appealing for a number of applications. PMID- 27378902 TI - VoxelStats: A MATLAB Package for Multi-Modal Voxel-Wise Brain Image Analysis. AB - In healthy individuals, behavioral outcomes are highly associated with the variability on brain regional structure or neurochemical phenotypes. Similarly, in the context of neurodegenerative conditions, neuroimaging reveals that cognitive decline is linked to the magnitude of atrophy, neurochemical declines, or concentrations of abnormal protein aggregates across brain regions. However, modeling the effects of multiple regional abnormalities as determinants of cognitive decline at the voxel level remains largely unexplored by multimodal imaging research, given the high computational cost of estimating regression models for every single voxel from various imaging modalities. VoxelStats is a voxel-wise computational framework to overcome these computational limitations and to perform statistical operations on multiple scalar variables and imaging modalities at the voxel level. VoxelStats package has been developed in Matlab((r)) and supports imaging formats such as Nifti-1, ANALYZE, and MINC v2. Prebuilt functions in VoxelStats enable the user to perform voxel-wise general and generalized linear models and mixed effect models with multiple volumetric covariates. Importantly, VoxelStats can recognize scalar values or image volumes as response variables and can accommodate volumetric statistical covariates as well as their interaction effects with other variables. Furthermore, this package includes built-in functionality to perform voxel-wise receiver operating characteristic analysis and paired and unpaired group contrast analysis. Validation of VoxelStats was conducted by comparing the linear regression functionality with existing toolboxes such as glim_image and RMINC. The validation results were identical to existing methods and the additional functionality was demonstrated by generating feature case assessments (t statistics, odds ratio, and true positive rate maps). In summary, VoxelStats expands the current methods for multimodal imaging analysis by allowing the estimation of advanced regional association metrics at the voxel level. PMID- 27378903 TI - An Automatic Method for Nucleus Boundary Segmentation Based on a Closed Cubic Spline. AB - The recognition of brain nuclei is the basis for localizing brain functions. Traditional histological research, represented by atlas illustration, achieves the goal of nucleus boundary recognition by manual delineation, but it has become increasingly difficult to extend this handmade method to delineating brain regions and nuclei from large datasets acquired by the recently developed single cell-resolution imaging techniques for the whole brain. Here, we propose a method based on a closed cubic spline (CCS), which can automatically segment the boundaries of nuclei that differ to a relatively high degree in cell density from the surrounding areas and has been validated on model images and Nissl-stained microimages of mouse brain. It may even be extended to the segmentation of target outlines on MRI or CT images. The proposed method for the automatic extraction of nucleus boundaries would greatly accelerate the illustration of high-resolution brain atlases. PMID- 27378904 TI - Stimulation of Synaptic Vesicle Exocytosis by the Mental Disease Gene DISC1 is Mediated by N-Type Voltage-Gated Calcium Channels. AB - Lesions and mutations of the DISC1 (Disrupted-in-schizophrenia-1) gene have been linked to major depression, schizophrenia, bipolar disorder and autism, but the influence of DISC1 on synaptic transmission remains poorly understood. Using two independent genetic approaches-RNAi and a DISC1 KO mouse-we examined the impact of DISC1 on the synaptic vesicle (SV) cycle by population imaging of the synaptic tracer vGpH in hippocampal neurons. DISC1 loss-of-function resulted in a marked decrease in SV exocytic rates during neuronal stimulation and was associated with reduced Ca(2+) transients at nerve terminals. Impaired SV release was efficiently rescued by elevation of extracellular Ca(2+), hinting at a link between DISC1 and voltage-gated Ca(2+) channels. Accordingly, blockade of N-type Cav2.2 channels mimics and occludes the effect of DISC1 inactivation on SV exocytosis, and overexpression of DISC1 in a heterologous system increases Cav2.2 currents. Collectively, these results show that DISC1-dependent enhancement of SV exocytosis is mediated by Cav2.2 and point to aberrant glutamate release as a probable endophenotype of major psychiatric disorders. PMID- 27378905 TI - A Comparison of Magnetic Resonance Imaging and Neuropsychological Examination in the Diagnostic Distinction of Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia. AB - The clinical distinction between Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) remains challenging and largely dependent on the experience of the clinician. This study investigates whether objective machine learning algorithms using supportive neuroimaging and neuropsychological clinical features can aid the distinction between both diseases. Retrospective neuroimaging and neuropsychological data of 166 participants (54 AD; 55 bvFTD; 57 healthy controls) was analyzed via a Naive Bayes classification model. A subgroup of patients (n = 22) had pathologically-confirmed diagnoses. Results show that a combination of gray matter atrophy and neuropsychological features allowed a correct classification of 61.47% of cases at clinical presentation. More importantly, there was a clear dissociation between imaging and neuropsychological features, with the latter having the greater diagnostic accuracy (respectively 51.38 vs. 62.39%). These findings indicate that, at presentation, machine learning classification of bvFTD and AD is mostly based on cognitive and not imaging features. This clearly highlights the urgent need to develop better biomarkers for both diseases, but also emphasizes the value of machine learning in determining the predictive diagnostic features in neurodegeneration. PMID- 27378906 TI - Aging Affects Neural Synchronization to Speech-Related Acoustic Modulations. AB - As people age, speech perception problems become highly prevalent, especially in noisy situations. In addition to peripheral hearing and cognition, temporal processing plays a key role in speech perception. Temporal processing of speech features is mediated by synchronized activity of neural oscillations in the central auditory system. Previous studies indicate that both the degree and hemispheric lateralization of synchronized neural activity relate to speech perception performance. Based on these results, we hypothesize that impaired speech perception in older persons may, in part, originate from deviances in neural synchronization. In this study, auditory steady-state responses that reflect synchronized activity of theta, beta, low and high gamma oscillations (i.e., 4, 20, 40, and 80 Hz ASSR, respectively) were recorded in young, middle aged, and older persons. As all participants had normal audiometric thresholds and were screened for (mild) cognitive impairment, differences in synchronized neural activity across the three age groups were likely to be attributed to age. Our data yield novel findings regarding theta and high gamma oscillations in the aging auditory system. At an older age, synchronized activity of theta oscillations is increased, whereas high gamma synchronization is decreased. In contrast to young persons who exhibit a right hemispheric dominance for processing of high gamma range modulations, older adults show a symmetrical processing pattern. These age-related changes in neural synchronization may very well underlie the speech perception problems in aging persons. PMID- 27378907 TI - Melodic Contour Identification Reflects the Cognitive Threshold of Aging. AB - Cognitive decline is a natural phenomenon of aging. Although there exists a consensus that sensitivity to acoustic features of music is associated with such decline, no solid evidence has yet shown that structural elements and contexts of music explain this loss of cognitive performance. This study examined the extent and the type of cognitive decline that is related to the contour identification task (CIT) using tones with different pitches (i.e., melodic contours). Both younger and older adult groups participated in the CIT given in three listening conditions (i.e., focused, selective, and alternating). Behavioral data (accuracy and response times) and hemodynamic reactions were measured using functional near infrared spectroscopy (fNIRS). Our findings showed cognitive declines in the older adult group but with a subtle difference from the younger adult group. The accuracy of the melodic CITs given in the target-like distraction task (CIT2) was significantly lower than that in the environmental noise (CIT1) condition in the older adult group, indicating that CIT2 may be a benchmark test for age-specific cognitive decline. The fNIRS findings also agreed with this interpretation, revealing significant increases in oxygenated hemoglobin (oxyHb) concentration in the younger (p < 0.05 for Deltapre - on task; p < 0.01 for Deltaon - post task) rather than the older adult group (n.s for Deltapre - on task; n.s for Deltaon - post task). We further concluded that the oxyHb difference was present in the brain regions near the right dorsolateral prefrontal cortex. Taken together, these findings suggest that CIT2 (i.e., the melodic contour task in the target like distraction) is an optimized task that could indicate the degree and type of age-related cognitive decline. PMID- 27378908 TI - Electrophysiology of Memory-Updating Differs with Age. AB - In oddball tasks, the P3 component of the event-related potential systematically varies with the time between target stimuli-the target-to-target interval (TTI). Longer TTIs result in larger P3 amplitudes and shorter latencies, and this pattern of results has been linked with working memory-updating processes. Given that working memory and the P3 have both been shown to diminish with age, the current study aimed to determine whether the linear relationship between P3 and TTI is compromised in healthy aging by comparing TTI effects on P3 amplitudes and latencies, and reaction time (RT), in young and older adults. Older adults were found to have an overall reduction in P3 amplitudes, longer latencies, an anterior shift in topography, a trend toward slower RTs, and a flatter linear relationship between P3 and TTI than young adults. Results suggest that the ability to maintain templates in working memory required for stimulus categorization decreases with age, and that as a result, neural compensatory mechanisms are employed. PMID- 27378909 TI - Progressive Bidirectional Age-Related Changes in Default Mode Network Effective Connectivity across Six Decades. AB - The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade cohorts (from 20-29 to 70-79). Structural equation modeling (SEM) was used to assess age related changes in inter-regional connectivity within the DMN. SEM was applied both using a previously published, meta-analytically derived, node-and-edge model, and using exploratory modeling searching for connections that optimized model fit improvement. Although the two models were highly similar (only 3 of 13 paths differed), the sample demonstrated significantly better fit with the exploratory model. For this reason, the exploratory model was used to assess age related changes across the decade cohorts. Progressive, highly significant changes in path weights were found in 8 (of 13) paths: four rising, and four falling (most changes were significant by the third or fourth decade). In all cases, rising paths and falling paths projected in pairs onto the same nodes, suggesting compensatory increases associated with age-related decreases. This study demonstrates that age-related changes in DMN physiology (inter-regional connectivity) are bidirectional, progressive, of early onset and part of normal aging. PMID- 27378910 TI - Etiologic Framework for the Study of Neurodegenerative Disorders as Well as Vascular and Metabolic Comorbidities on the Grounds of Shared Epidemiologic and Biologic Features. AB - BACKGROUND: During the last two decades, protein aggregation at all organismal levels, from viruses to humans, has emerged from a neglected area of protein science to become a central issue in biology and biomedicine. This article constitutes a risk-based review aimed at supporting an etiologic scenario of selected, sporadic, protein-associated, i.e., conformational, neurodegenerative disorders (NDDs), and their vascular- and metabolic-associated ailments. METHODS: A rationale is adopted, to incorporate selected clinical data and results from animal-model research, complementing epidemiologic evidences reported in two prior articles. FINDINGS: Theory is formulated assuming an underlying conformational transmission mechanism, mediated either by horizontal transfer of mammalian genes coding for specific aggregation-prone proteins, or by xeno templating between bacterial and host proteins. We build a few population-based and experimentally-testable hypotheses focusing on: (1) non-disposable surgical instruments for sporadic Creutzfeldt-Jakob disease (sCJD) and other rapid progressive neurodegenerative dementia (sRPNDd), multiple system atrophy (MSA), and motor neuron disease (MND); and (2) specific bacterial infections such as B. pertussis and E. coli for all forms, but particularly for late-life sporadic conformational, NDDs, type 2 diabetes mellitus (T2DM), and atherosclerosis where natural protein fibrils present in such organisms as a result of adaptation to the human host induce prion-like mechanisms. CONCLUSION: Implications for cohort alignment and experimental animal research are discussed and research lines proposed. PMID- 27378912 TI - Over-Expressed Pathogenic miRNAs in Alzheimer's Disease (AD) and Prion Disease (PrD) Drive Deficits in TREM2-Mediated Abeta42 Peptide Clearance. AB - One prominent and distinguishing feature of progressive, age-related neurological diseases such as Alzheimer's disease (AD) and prion disease (PrD) is the gradual accumulation of amyloids into dense, insoluble end-stage protein aggregates. These polymorphic proteolipid lesions are known to contribute to immunogenic and inflammatory pathology in these insidious and fatal disorders of the human central nervous system (CNS). For example, the evolution of self-aggregating amyloid-beta (Abeta) peptides, such as the 42 amino acid Abeta42 peptide monomer into higher order aggregates are largely due to: (1) the inability of natural processes to clear them from the cellular environment; and/or (2) the overproduction of these amyloid monomers which rapidly mature into higher order oligomers, fibrils and insoluble, end-stage senile plaques. Cells of the CNS such as microglial (MG) cells have evolved essential homeostatic mechanisms to clear Abeta peptides to avoid their accumulation, however, when defective, these clearance mechanisms become overwhelmed and excessive deposition and aggregation of these amyloids result. This 'Perspectives' paper will highlight some emerging concepts on the up-regulation of an inducible microRNA-34a in AD and PrD that drives the down-regulation of the amyloid sensing- and clearance receptor protein TREM2 (the triggering receptor expressed in myeloid/microglial cells). The impairment of this inducible, miRNA-34a-regulated TREM2- and MG-cell based amyloid clearance mechanism may thereby contribute to the age-related amyloidogenesis associated with both AD and PrD. PMID- 27378911 TI - Magnetic Resonance Imaging to Detect Early Molecular and Cellular Changes in Alzheimer's Disease. AB - Recent pharmaceutical trials have demonstrated that slowing or reversing pathology in Alzheimer's disease is likely to be possible only in the earliest stages of disease, perhaps even before significant symptoms develop. Pathology in Alzheimer's disease accumulates for well over a decade before symptoms are detected giving a large potential window of opportunity for intervention. It is therefore important that imaging techniques detect subtle changes in brain tissue before significant macroscopic brain atrophy. Current diagnostic techniques often do not permit early diagnosis or are too expensive for routine clinical use. Magnetic Resonance Imaging (MRI) is the most versatile, affordable, and powerful imaging modality currently available, being able to deliver detailed analyses of anatomy, tissue volumes, and tissue state. In this mini-review, we consider how MRI might detect patients at risk of future dementia in the early stages of pathological change when symptoms are mild. We consider the contributions made by the various modalities of MRI (structural, diffusion, perfusion, relaxometry) in identifying not just atrophy (a late-stage AD symptom) but more subtle changes reflective of early dementia pathology. The sensitivity of MRI not just to gross anatomy but to the underlying "health" at the cellular (and even molecular) scales, makes it very well suited to this task. PMID- 27378913 TI - Editorial: A Hand at Work: Effects of Aging. PMID- 27378914 TI - Mortality, Recurrence, and Dependency Rates Are Higher after Acute Ischemic Stroke in Elderly Patients with Diabetes Compared to Younger Patients. AB - Stroke has a greater effect on the elderly than on younger patients. However, the long-term outcomes associated with stroke among elderly patients with diabetes are unknown. We aimed to assess the differences in long-term outcomes between young and elderly stroke patients with diabetes. A total of 3,615 acute ischemic stroke patients with diabetes were recruited for this study between 2006 and 2014. Outcomes at 12 and 36 months after stroke (including mortality, recurrence, and dependency) were compared between younger (age <75 years) and elderly (age >=75 years) patients. The elderly group included 692 patients (19.1%) overall. Elderly patients were more likely than younger patients to have a Trial of Org 10172 in Acute Stroke Treatment classification of stroke due to cardioembolism, moderate and severe stroke, and atrial fibrillation, but less likely to have hypertension and dyslipidemia, current smokers, and alcohol consumers. Mortality, dependency, and recurrence rates at 12 months after stroke were 19.0, 48.5, and 20.9% in the elderly group and 7.4, 30.9, and 15.4% in the younger group, respectively (all P < 0.05). Corresponding rates at 36 months after stroke were 35.4, 78.7, and 53.8% in the elderly group and 13.7, 61.7, and 43.0% in the younger group, respectively (all P < 0.001). The mortality, dependency, and recurrence rates at 12 and 36 months after stroke were significantly higher in the elderly group than in the younger group after adjusting for stroke subtypes, stroke severity, and risk factors. Odds ratios (95% confidence interval) at 12 and 36 months after stroke were 2.18 (1.64-2.89) and 3.10 (2.35-4.08), respectively, for mortality, all P < 0.001; 1.81 (1.49-2.20) and 2.04 (1.57 2.34), respectively, for dependency, all P < 0.001; and 1.37 (1.06-1.76) and 1.40 (1.07-1.85), respectively, for recurrence, P = 0.016. The findings from this study suggest that management and secondary prevention should be emphasized in elderly patients with diabetes in China to reduce mortality, recurrence, and dependency after stroke. PMID- 27378915 TI - The Association of Aging with White Matter Integrity and Functional Connectivity Hubs. AB - Normal aging is associated with reduced cerebral structural integrity and altered functional brain activity, yet the association of aging with the relationship between structural and functional brain changes remains unclear. Using combined diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) modalities, we hypothesized that aging-related changes in white matter integrity (i.e., fractional anisotropy) was associated with the short- or long-range functional connectivity density (FCD) in hub regions. We tested this hypothesis by using a healthy aging cohort comprised of 140 younger adults aged 20-39 years and 109 older adults aged 60-79 years. Compared with the younger group, older adults exhibited widespread reductions in white matter integrity with selective preservation in brain stem tracts and the cingulum connected to the hippocampus and cingulate cortex, whereas FCD mapping in older adults showed a reduced FCD in the visual, somatosensory, and motor functional networks and an increased FCD in the default mode network. The older adults exhibited significantly increased short- or long-range FCD in functional hubs of the precuneus, posterior, and middle cingulate, and thalamus, hippocampus, fusiform, and inferior temporal cortex. Furthermore, DTI-fMRI relationship were predominantly identified in older adults in whom short- and long-range FCD in the left precuneus was negatively correlated to structural integrity of adjacent and nonadjacent white matter tracts, respectively. We also found that long-range FCD in the left precuneus was positively correlated to cognitive function. These results support the compensatory hypothesis of neurocognitive aging theory and reveal the DTI-fMRI relationship associated with normal aging. PMID- 27378916 TI - Pharmacotherapy of Pain in the Older Population: The Place of Opioids. AB - Pain is a common symptom in older people. It is possible that pain is underreported in older persons due to an incorrect belief that it is an inevitable part of aging. Opioid analgesics are potent medications, with confirmed efficacy for the treatment of moderate to severe pain. These drugs are commonly used in older persons. However, there is insufficient evidence regarding safety of opioids in older patients. One of the reasons for this is the lack of randomized, controlled clinical trials. People of advanced age often have comorbidites and use other prescription drugs, as well as over-the-counter (OTC) compounds, thus making them more suceptible to the risk of interactions with opioids. Significant pharmacokinetic and pharmacodynamic changes that occur with advancing age increase the risk of adverse effects of opioids. There are also some discrepancies between guidelines, which recommend the use of lower doses of opioids in older patients, and the findings in the literature which suggest that pain is often undertreated in this age group. It seems that there are significant variations in the tolerability of different opioid analgesics in older people. Morphine, fentanyl, oxycodone, and buprenorphine are still the preferred evidence based choices for add-on opioid therapy for these patients. However, the safety and efficacy of other opioids in older patients, especially if comorbidities and polypharmacy are present, is still questionable. This review addresses the most important aspects of the use of opioids in older persons, focusing on pharmacokinetics, pharmacodynamics, adverse effects, and interactions. PMID- 27378918 TI - Corrigendum: The Busier the Better: Greater Busyness Is Associated with Better Cognition. AB - [This corrects the article on p. 98 in vol. 8, PMID: 27242510.]. PMID- 27378917 TI - Hippocampal Amyloid Burden with Downstream Fusiform Gyrus Atrophy Correlate with Face Matching Task Scores in Early Stage Alzheimer's Disease. AB - PURPOSE: Neuronal activity during face matching shows co-activation of the fusiform gyrus (FG) and areas along the ventral visual network. To elucidate the mechanisms related to the facial discrimination deficits in Alzheimer's disease (AD), the study evaluates the relationships between beta-amyloid (Abeta) load and gray matter (GM) atrophy within the ventral visual network. METHODS: Comprehensive cognitive assessments and GM volumetry using 3-dimentional T1 weighted images and AV-45 positron emission tomography (PET) were studied in 44 patients with AD. We used AV-45 PET to measure regional Abeta to analyze the correlations between the regional neocortical AV-45 retention and atrophy in patients with AD. RESULTS: FG volume was positively correlated with the para hippocampus (beta = 0.565, P < 0.001), posterior cingulate cortex (PCC; beta = 0.402, P < 0.001), and hippocampus volumes (beta = 0.209, P = 0.044). After carefully confounded all possible factors simultaneously, the hippocampus standardized uptake value (SUV) ratio was independently associated with FG volume (beta = -0.151, P = 0.017). Furthermore, volumes of the hippocampus (r = 0.473, P = 0.003), para-hippocampus (r = 0.515, P = 0.001), and FG (r = 0.383, P = 0.018) were associated with Benton's facial recognition test (BFRT). CONCLUSIONS: In conclusion, our study indicated that amyloid burden within the hippocampus might contribute to FG cortical hub GM atrophy. While the face matching task scores were related to the FG, hippocampus, and para-hippocampus volumes, concordant changes of the aforementioned three structures suggested the importance of the three ventral visual network hubs in AD. PMID- 27378919 TI - Pharmacometabolomic Assessment of Metformin in Non-diabetic, African Americans. AB - Millions of individuals are diagnosed with type 2 diabetes mellitus (T2D), which increases the risk for a plethora of adverse outcomes including cardiovascular events and kidney disease. Metformin is the most widely prescribed medication for the treatment of T2D; however, its mechanism is not fully understood and individuals vary in their response to this therapy. Here, we use a non-targeted, pharmacometabolomics approach to measure 384 metabolites in 33 non-diabetic, African American subjects dosed with metformin. Three plasma samples were obtained from each subject, one before and two after metformin administration. Validation studies were performed in wildtype mice given metformin. Fifty-four metabolites (including 21 unknowns) were significantly altered upon metformin administration, and 12 metabolites (including six unknowns) were significantly associated with metformin-induced change in glucose (q < 0.2). Of note, indole-3 acetate, a metabolite produced by gut microbes, and 4-hydroxyproline were modulated following metformin exposure in both humans and mice. 2-Hydroxybutanoic acid, a metabolite previously associated with insulin resistance and an early biomarker of T2D, was positively correlated with fasting glucose levels as well as glucose levels following oral glucose tolerance tests after metformin administration. Pathway analysis revealed that metformin administration was associated with changes in a number of metabolites in the urea cycle and in purine metabolic pathways (q < 0.01). Further research is needed to validate the biomarkers of metformin exposure and response identified in this study, and to understand the role of metformin in ammonia detoxification, protein degradation and purine metabolic pathways. PMID- 27378920 TI - Extracted Triterpenes from Antrodia cinnamomea Reduce the Inflammation to Promote the Wound Healing via the STZ Inducing Hyperglycemia-Diabetes Mice Model. AB - This research evaluated the effects of triterpenes on the regulation of STZ induced hyperglycaemic diabetes through an anti-inflammatory response. Diabetic mice were orally administered various concentrations of triterpenes on a daily basis. Weight gain, volume of drinking water, and liver and spleen weight were recorded and evaluated. These evaluations presented a positive regulation to the abnormal metabolism appearance compared to the diabetic mice. In the diabetic mice, the detection of adiponectin production or elevated levels of inflammatory factors such as CCL1 and TPO expression were found to reduce hyperglycaemia and thereby induce an inflammatory response. Moreover, to the best of our knowledge, hyperglycaemia impairs the tissue healing associated with an increased and prolonged inflammatory response. An investigation of the anti-inflammatory response in wound healing as affected by the triterpenes verified the promotion of wound recovery. PMID- 27378921 TI - MinION: A Novel Tool for Predicting Drug Hypersensitivity? AB - The launch of the MinION Access Program has caused much activity within the scientific community. MinION represents a keenly anticipated, novel addition to the current melange of commercial sequencers. Driven by the nanopore sequencing mechanism that requires minimal sample manipulation, the device is capable of generating long sequence reads in sizes (up to or exceeding 50 kb) that surpass those of all other platforms. One notable advantage of this feature is that long range haplotypes can be more accurately resolved; such advantage is particularly pertinent to the genotyping of complex loci such as genes encoding the human leukocyte antigens, which are pivotal determinants of drug hypersensitivity. With this timely, albeit brief, review, we set out to examine the applications on which MinION has been tested thus far, the bioinformatics workflow tailored to the unique characteristics of its extended sequence reads, the device's potential utility in the detection of genetic markers for drug hypersensitivity, and how it may eventually evolve to become fit for diagnostic purposes in the clinical setting. PMID- 27378922 TI - Multitarget Multiscale Simulation for Pharmacological Treatment of Dystonia in Motor Cortex. AB - A large number of physiomic pathologies can produce hyperexcitability in cortex. Depending on severity, cortical hyperexcitability may manifest clinically as a hyperkinetic movement disorder or as epilpesy. We focus here on dystonia, a movement disorder that produces involuntary muscle contractions and involves pathology in multiple brain areas including basal ganglia, thalamus, cerebellum, and sensory and motor cortices. Most research in dystonia has focused on basal ganglia, while much pharmacological treatment is provided directly at muscles to prevent contraction. Motor cortex is another potential target for therapy that exhibits pathological dynamics in dystonia, including heightened activity and altered beta oscillations. We developed a multiscale model of primary motor cortex, ranging from molecular, up to cellular, and network levels, containing 1715 compartmental model neurons with multiple ion channels and intracellular molecular dynamics. We wired the model based on electrophysiological data obtained from mouse motor cortex circuit mapping experiments. We used the model to reproduce patterns of heightened activity seen in dystonia by applying independent random variations in parameters to identify pathological parameter sets. These models demonstrated degeneracy, meaning that there were many ways of obtaining the pathological syndrome. There was no single parameter alteration which would consistently distinguish pathological from physiological dynamics. At higher dimensions in parameter space, we were able to use support vector machines to distinguish the two patterns in different regions of space and thereby trace multitarget routes from dystonic to physiological dynamics. These results suggest the use of in silico models for discovery of multitarget drug cocktails. PMID- 27378923 TI - The Guanine-Based Purinergic System: The Tale of An Orphan Neuromodulation. AB - Guanine-based purines (GBPs) have been recently proposed to be not only metabolic agents but also extracellular signaling molecules that regulate important functions in the central nervous system. In such way, GBPs-mediated neuroprotection, behavioral responses and neuronal plasticity have been broadly described in the literature. However, while a number of these functions (i.e., GBPs neurothophic effects) have been well-established, the molecular mechanisms behind these GBPs-dependent effects are still unknown. Furthermore, no plasma membrane receptors for GBPs have been described so far, thus GBPs are still considered orphan neuromodulators. Interestingly, an intricate and controversial functional interplay between GBPs effects and adenosine receptors activity has been recently described, thus triggering the hypothesis that GBPs mechanism of action might somehow involve adenosine receptors. Here, we review recent data describing the GBPs role in the brain. We focus on the involvement of GBPs regulating neuronal plasticity, and on the new hypothesis based on putative GBPs receptors. Overall, we expect to shed some light on the GBPs world since although these molecules might represent excellent candidates for certain neurological diseases management, the lack of putative GBPs receptors precludes any high throughput screening intent for the search of effective GBPs-based drugs. PMID- 27378925 TI - Downregulation of GSTK1 Is a Common Mechanism Underlying Hypertrophic Cardiomyopathy. AB - Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and is associated with a number of potential outcomes, including impaired diastolic function, heart failure, and sudden cardiac death. Various etiologies have been described for HCM, including pressure overload and mutations in sarcomeric and non-sarcomeric genes. However, the molecular pathogenesis of HCM remains incompletely understood. In this study, we performed comparative transcriptome analysis to identify dysregulated genes common to five mouse HCM models of differing etiology: (i) mutation of myosin heavy chain 6, (ii) mutation of tropomyosin 1, (iii) expressing human phospholamban on a null background, (iv) knockout of frataxin, and (v) transverse aortic constriction. Gene-by-gene comparison identified five genes dysregulated in all five HCM models. Glutathione S-transferase kappa 1 (Gstk1) was significantly downregulated in the five models, whereas myosin heavy chain 7 (Myh7), connective tissue growth factor (Ctgf), periostin (Postn), and reticulon 4 (Rtn4) were significantly upregulated. Gene ontology comparison revealed that 51 cellular processes were significantly enriched in genes dysregulated in each transcriptome dataset. Among them, six processes (oxidative stress, aging, contraction, developmental process, cell differentiation, and cell proliferation) were related to four of the five genes dysregulated in all HCM models. GSTK1 was related to oxidative stress only, whereas the other four genes were related to all six cell processes except MYH7 for oxidative stress. Gene-gene functional interaction network analysis suggested correlative expression of GSTK1, MYH7, and actin alpha 2 (ACTA2). To investigate the implications of Gstk1 downregulation for cardiac function, we knocked out gstk1 in zebrafish using the clustered regularly interspaced short palindromic repeats/Cas9 system. We found that expression of the zebrafish homologs of MYH7, ACTA2, and actin alpha 1 were increased in the gstk1-knockout zebrafish. In vivo imaging of zebrafish expressing a fluorescent protein in cardiomyocytes showed that gstk1 deletion significantly decreased the end diastolic volume and, to a lesser extent, end systolic volume. These results suggest that downregulation of GSTK1 may be a common mechanism underlying HCM of various etiologies, possibly through increasing oxidative stress and the expression of sarcomere genes. PMID- 27378926 TI - Toxic Constituents Index: A Toxicity-Calibrated Quantitative Evaluation Approach for the Precise Toxicity Prediction of the Hypertoxic Phytomedicine-Aconite. AB - Complex chemical composition is an important reason for restricting herbal quality evaluation. Despite the multi-components determination method significantly promoted the progress of herbal quality evaluation, however, which mainly concerned the total amount of multiple components and ignored the activity variation between each one, and did not accurately reflect the biological activity of botanical medicines. In this manuscript, we proposed a toxicity calibrated contents determination method for hyper toxic aconite, called toxic constituents index (TCI). Initially, we determined the minimum lethal dose value of mesaconitine (MA), aconitine (AC), and hypaconitine (HA), and established the equation TCI = 100 * (0.3387 *X MA + 0.4778 *X AC + 0.1835 *X HA). Then, 10 batches of aconite were selected and their evaluation results of toxic potency (TP), diester diterpenoid alkaloids (DDAs), and TCI were compared. Linear regression analysis result suggested that the relevance between TCI and TP was the highest and the correlation coefficient R was 0.954. Prediction error values study also indicated that the evaluation results of TCI was highly consistent with that of TP. Moreover, TCI and DDAs were both applied to evaluate 14 batches of aconite samples oriented different origins; from the different evaluation results, we found when the proportion of HA was reached 25% in DDAs, the pharmacopeia method could generate false positive results. All these results testified the accuracy and universality of TCI method. We believe that this study method is rather accurate, simple, and easy operation and it will be of great utility in studies of other foods and herbs. PMID- 27378927 TI - Anti-Inflammatory Properties of Menthol and Menthone in Schistosoma mansoni Infection. AB - Schistosomiasis is a parasitic disease caused by several species of trematode worms and it is believed that more than 261 million people are affected worldwide. New drug development has become essential because there is a risk of the parasite becoming resistant to Praziquantel, the only drug available for this infection. This study evaluated parasitological, immunological and histological parameters in mice infected with Schistosoma mansoni and treated with an herbal commercial medicine. This drug consists of menthol (30-55%) and menthone (14 32%). A 60 day treatment regimen with the herbal medicine decreased the number of S. mansoni eggs in the feces, liver, and intestine and reduced the number of hepatic granulomas. We observed a reduction of 84% in blood eosinophilia and a decrease in the IL-4 and IL-10 blood levels after treatment. Therefore, we propose that schistosomiasis treatment with this herbal medicine for 60 days has an immunomodulatory and anti-inflammatory action in this animal model for schistosomiasis thus contributing to the decrease in physio pathological effects caused by S. mansoni infection. PMID- 27378924 TI - Non-invasive Markers of Liver Fibrosis: Adjuncts or Alternatives to Liver Biopsy? AB - Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an imperfect test and poorly accepted by patients. The development of robust tools to non-invasively assess liver fibrosis has dramatically enhanced clinical decision making in patients with chronic liver disease, allowing a rapid and informed judgment of disease stage and prognosis. Should a liver biopsy be required, the appropriateness is clearer and the diagnostic yield is greater with the use of these adjuncts. While a number of non invasive liver fibrosis markers are now used in routine practice, a steady stream of innovative approaches exists. With improvement in the reliability, reproducibility and feasibility of these markers, their potential role in disease management is increasing. Moreover, their adoption into clinical trials as outcome measures reflects their validity and dynamic nature. This review will summarize and appraise the current and novel non-invasive markers of liver fibrosis, both blood and imaging based, and look at their prospective application in everyday clinical care. PMID- 27378928 TI - Basophil Reactivity as Biomarker in Immediate Drug Hypersensitivity Reactions Potential and Limitations. AB - Immediate drug hypersensitivity reactions (DHRs) resemble typical immunoglobulin E (IgE)-mediated symptoms. Clinical manifestations range from local skin reactions, gastrointestinal and/or respiratory symptoms to severe systemic involvement with potential fatal outcome. Depending on the substance group of the eliciting drug the correct diagnosis is a major challenge. Skin testing and in vitro diagnostics are often unreliable and not reproducible. The involvement of drug-specific IgE is questionable in many cases. The culprit substance (parent drug or metabolite) and potential cross-reacting compounds are difficult to identify, patient history and drug provocation testing often remain the only means for diagnosis. Hence, several groups proposed basophil activation test (BAT) for the diagnosis of immediate DHRs as basophils are well-known effector cells in allergic reactions. However, the usefulness of BAT in immediate DHRs is highly variable and dependent on the drug itself plus its capacity to spontaneously conjugate to serum proteins. Stimulation with pure solutions of the parent drug or metabolites thereof vs. drug-protein conjugates may influence sensitivity and specificity of the test. We thus, reviewed the available literature about the use of BAT for diagnosing immediate DHRs against drug classes such as antibiotics, radio contrast media, neuromuscular blocking agents, non-steroidal anti-inflammatory drugs, and biologicals. Influencing factors like the selection of stimulants or of the identification and activation markers, the stimulation protocol, gating strategies, and cut-off definition are addressed in this overview on BAT performance. The overall aim is to evaluate the suitability of BAT as biomarker for the diagnosis of immediate drug-induced hypersensitivity reactions. PMID- 27378929 TI - The Relation between Hepatotoxicity and the Total Coumarin Intake from Traditional Japanese Medicines Containing Cinnamon Bark. AB - Cinnamon bark is commonly used in traditional Japanese herbal medicines (Kampo medicines). The coumarin contained in cinnamon is known to be hepatotoxic, and a tolerable daily intake (TDI) of 0.1 mg/kg/day, has been quantified and used in Europe to insure safety. Risk assessments for hepatotoxicity by the cinnamon contained in foods have been reported. However, no such assessment of cinnamon bark has been reported and the coumarin content of Kampo medicines derived from cinnamon bark is not yet known. To assess the risk for hepatotoxicity by Kampo medicines, we evaluated the daily coumarin intake of patients who were prescribed Kampo medicines and investigated the relation between hepatotoxicity and the coumarin intake. The clinical data of 129 outpatients (18 male and 111 female, median age 58 years) who had been prescribed keishibukuryogankayokuinin (TJ-125) between April 2008 and March 2013 was retrospectively investigated. Concurrent Kampo medicines and liver function were also surveyed. In addition to TJ-125, the patients took some of the other 32 Kampo preparations and 22 decoctions that include cinnamon bark. The coumarin content of these Kampo medicines was determined by high performance liquid chromatography (HPLC). TJ-125 had the highest daily content of coumarin (5.63 mg/day), calculated from the daily cinnamon bark dosage reported in the information leaflet inserted in each package of Kampo medicine. The coumarin content in 1g cinnamon bark decoction was 3.0 mg. The daily coumarin intake of the patients was 0.113 (0.049-0.541) mg/kg/day, with 98 patients (76.0%) exceeding the TDI. Twenty-three patients had an abnormal change in liver function test value, but no significant difference was found in the incidence of abnormal change between the group consuming less than the TDI value (6/31, 19.4%) and the group consuming equal to or greater than the TDI value (17/98, 17.3%). In addition, no abnormal change related to cinnamon bark was found for individual patients. This paper was done to assess the risk of hepatotoxicity by the coumarin contained in Kampo medicines and to clarify whether or not the Kampo preparations in general use that contain cinnamon bark may be safely used in clinical practice. PMID- 27378930 TI - Expression of Concern: Mechanism of Action of the Novel Nickel(II) Complex in Simultaneous Reactivation of the Apoptotic Signaling Networks Against Human Colon Cancer Cells. PMID- 27378931 TI - Cancer Markers Selection Using Network-Based Cox Regression: A Methodological and Computational Practice. AB - International initiatives such as the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) are collecting multiple datasets at different genome-scales with the aim of identifying novel cancer biomarkers and predicting survival of patients. To analyze such data, several statistical methods have been applied, among them Cox regression models. Although these models provide a good statistical framework to analyze omic data, there is still a lack of studies that illustrate advantages and drawbacks in integrating biological information and selecting groups of biomarkers. In fact, classical Cox regression algorithms focus on the selection of a single biomarker, without taking into account the strong correlation between genes. Even though network based Cox regression algorithms overcome such drawbacks, such network-based approaches are less widely used within the life science community. In this article, we aim to provide a clear methodological framework on the use of such approaches in order to turn cancer research results into clinical applications. Therefore, we first discuss the rationale and the practical usage of three recently proposed network-based Cox regression algorithms (i.e., Net-Cox, AdaLnet, and fastcox). Then, we show how to combine existing biological knowledge and available data with such algorithms to identify networks of cancer biomarkers and to estimate survival of patients. Finally, we describe in detail a new permutation-based approach to better validate the significance of the selection in terms of cancer gene signatures and pathway/networks identification. We illustrate the proposed methodology by means of both simulations and real case studies. Overall, the aim of our work is two-fold. Firstly, to show how network based Cox regression models can be used to integrate biological knowledge (e.g., multi-omics data) for the analysis of survival data. Secondly, to provide a clear methodological and computational approach for investigating cancers regulatory networks. PMID- 27378933 TI - The Stress and Vascular Catastrophes in Newborn Rats: Mechanisms Preceding and Accompanying the Brain Hemorrhages. AB - In this study, we analyzed the time-depended scenario of stress response cascade preceding and accompanying brain hemorrhages in newborn rats using an interdisciplinary approach based on: a morphological analysis of brain tissues, coherent-domain optical technologies for visualization of the cerebral blood flow, monitoring of the cerebral oxygenation and the deformability of red blood cells (RBCs). Using a model of stress-induced brain hemorrhages (sound stress, 120 dB, 370 Hz), we studied changes in neonatal brain 2, 4, 6, 8 h after stress (the pre-hemorrhage, latent period) and 24 h after stress (the post-hemorrhage period). We found that latent period of brain hemorrhages is accompanied by gradual pathological changes in systemic, metabolic, and cellular levels of stress. The incidence of brain hemorrhages is characterized by a progression of these changes and the irreversible cell death in the brain areas involved in higher mental functions. These processes are realized via a time-depended reduction of cerebral venous blood flow and oxygenation that was accompanied by an increase in RBCs deformability. The significant depletion of the molecular layer of the prefrontal cortex and the pyramidal neurons, which are crucial for associative learning and attention, is developed as a consequence of homeostasis imbalance. Thus, stress-induced processes preceding and accompanying brain hemorrhages in neonatal period contribute to serious injuries of the brain blood circulation, cerebral metabolic activity and structural elements of cognitive function. These results are an informative platform for further studies of mechanisms underlying stress-induced brain hemorrhages during the first days of life that will improve the future generation's health. PMID- 27378934 TI - The Therapeutic Potential of Targeting Cytokine Alarmins to Treat Allergic Airway Inflammation. AB - Asthma is a heterogeneous disorder that results in recurrent attacks of breathlessness, coughing, and wheezing that affects millions of people worldwide. Although the precise causes of asthma are unclear, studies suggest that a combination of genetic predisposition and environmental exposure to various allergens and pathogens contribute to its development. Currently, the most common treatment to control asthma is a dual combination of beta2-adrenergic receptor agonists and corticosteroids. However, studies have shown that some patients do not respond well to these medications, while others experience significant side effects. It is reported that the majority of asthmas are associated with T helper type 2 (TH2) responses. In these patients, allergen challenge initiates the influx of TH2 cells in the airways leading to an increased production of TH2 associated cytokines and the promotion of allergy-induced asthma. Therefore, biologics that target this pathway may provide an alternative method to treat the allergic airway inflammation associated with asthma. As of now, only two biologics (omalizumab and mepolizumab), which target immunoglobulin E and interleukin-5, respectively, are FDA-approved and being prescribed to asthmatics. However, recent studies have reported that targeting other components of the TH2 response also show great promise. In this review, we will briefly describe the immunologic mechanisms underlying allergic asthma. Furthermore, we will discuss the current therapeutic strategies used to treat asthma including their limitations. Finally, we will highlight the benefits of using biologics to treat asthma-associated allergic airway inflammation with an emphasis on the potential of targeting cytokine alarmins, especially thymic stromal lymphopoietin. PMID- 27378932 TI - Insights into the Pathology of the alpha3 Na(+)/K(+)-ATPase Ion Pump in Neurological Disorders; Lessons from Animal Models. AB - The transmembrane Na(+)-/K(+) ATPase is located at the plasma membrane of all mammalian cells. The Na(+)-/K(+) ATPase utilizes energy from ATP hydrolysis to extrude three Na(+) cations and import two K(+) cations into the cell. The minimum constellation for an active Na(+)-/K(+) ATPase is one alpha (alpha) and one beta (beta) subunit. Mammals express four alpha isoforms (alpha1-4), encoded by the ATP1A1-4 genes, respectively. The alpha1 isoform is ubiquitously expressed in the adult central nervous system (CNS) whereas alpha2 primarily is expressed in astrocytes and alpha3 in neurons. Na(+) and K(+) are the principal ions involved in action potential propagation during neuronal depolarization. The alpha1 and alpha3 Na(+)-/K(+) ATPases are therefore prime candidates for restoring neuronal membrane potential after depolarization and for maintaining neuronal excitability. The alpha3 isoform has approximately four-fold lower Na(+) affinity compared to alpha1 and is specifically required for rapid restoration of large transient increases in [Na(+)]i. Conditions associated with alpha3 deficiency are therefore likely aggravated by suprathreshold neuronal activity. The alpha3 isoform been suggested to support re-uptake of neurotransmitters. These processes are required for normal brain activity, and in fact autosomal dominant de novo mutations in ATP1A3 encoding the alpha3 isoform has been found to cause the three neurological diseases Rapid Onset Dystonia Parkinsonism (RDP), Alternating Hemiplegia of Childhood (AHC), and Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS). All three diseases cause acute onset of neurological symptoms, but the predominant neurological manifestations differ with particularly early onset of hemiplegic/dystonic episodes and mental decline in AHC, ataxic encephalopathy and impairment of vision and hearing in CAPOS syndrome and late onset of dystonia/parkinsonism in RDP. Several mouse models have been generated to study the in vivo consequences of Atp1a3 modulation. The different mice show varying degrees of hyperactivity, gait problems, and learning disability as well as stress-induced seizures. With the advent of several Atp1a3-gene or chemically modified animal models that closely phenocopy many aspects of the human disorders, we will be able to reach a much better understanding of the etiology of RDP, AHC, and CAPOS syndrome. PMID- 27378935 TI - Swimming Training Modulates Nitric Oxide-Glutamate Interaction in the Rostral Ventrolateral Medulla in Normotensive Conscious Rats. AB - We evaluated the effects of swimming training on nitric oxide (NO) modulation to glutamate microinjection within the rostral ventrolateral medulla (RVLM) in conscious freely moving rats. Male Wistar rats were submitted to exercise training (Tr) by swimming or kept sedentary (Sed) for 4 weeks. After the last training session, RVLM guide cannulas and arterial/venous catheters were chronically implanted. Arterial pressure (AP), heart rate (HR), and baroreflex control of HR (loading/unloading of baroreceptors) were recorded in conscious rats at rest. Pressor response to L-glutamate in the RVLM was compared before and after blockade of local nitric oxide (NO) production. In other Tr and Sed groups, brain was harvested for gene (qRT-PCR) and protein (immunohistochemistry) expression of NO synthase (NOS) isoforms and measurement of NO content (nitrite assay) within the RVLM. Trained rats exhibited resting bradycardia (average reduction of 9%), increased baroreflex gain (Tr: -4.41 +/- 0.5 vs. Sed: -2.42 +/- 0.31 b/min/mmHg), and unchanged resting MAP. The pressor response to glutamate was smaller in the Tr group (32 +/- 4 vs. 53 +/- 2 mmHg, p < 0.05); this difference disappeared after RVLM pretreatment with carboxy-PTIO (NO scavenger), Nw-Propyl-L-Arginine and L-NAME (NOS inhibitors). eNOS immunoreactivity observed mainly in RVLM capillaries was higher in Tr, but eNOS gene expression was reduced. nNOS gene and protein expression was slightly reduced (-29 and -9%, respectively, P > 0.05). Also, RVLM NO levels were significantly reduced in Tr ( 63% vs. Sed). After microinjection of a NO-donor, the attenuated pressor response of L-glutamate in Tr group was restored. Data indicate that swimming training by decreasing RVLM NO availability and glutamatergic neurotransmission to locally administered glutamate may contribute to decreased sympathetic activity in trained subjects. PMID- 27378936 TI - Chronic Omega-3 Polyunsaturated Fatty Acid Treatment Variably Affects Cellular Repolarization in a Healed Post-MI Arrhythmia Model. AB - INTRODUCTION: Over the last 40 years omega-3 polyunsaturated fatty acids (PUFAs) have been shown to be anti-arrhythmic or pro-arrhythmic depending on the method and duration of administration and model studied. We previously reported that omega-3 PUFAs do not confer anti-arrhythmic properties and are pro-arrhythmic in canine model of sudden cardiac death (SCD). Here, we evaluated the effects of chronic omega-3 PUFA treatment in post-MI animals susceptible (VF+) or resistant (VF-) to ventricular tachyarrhythmias. METHODS: Perforated patch clamp techniques were used to measure cardiomyocyte action potential durations (APD) at 50 and 90% repolarization and short term variability of repolarization. The early repolarizing transient outward potassium current Ito was also studied. RESULTS: Omega-3 PUFAs prolonged the action potential in VF- myocytes at both 50 and 90% repolarization. Short term variability of repolarization was increased in both untreated and treated VF- myocytes vs. CONTROLS: Ito was unaffected by omega-3 PUFA treatment. Omega-3 PUFA treatment attenuated the action potential prolongation in VF+ myocytes, but did not return repolarization to control values. CONCLUSIONS: Omega-3 PUFAs do not confer anti-arrhythmic properties in the setting of healed myocardial infarction in a canine model of SCD. In canines previously resistant to ventricular fibrillation (VF-), omega-3 PUFA treatment prolonged the action potential in VF- myocytes, and may contribute to pro arrhythmic responses. PMID- 27378937 TI - Uninephrectomy-Induced Lipolysis and Low-Grade Inflammation Are Mimicked by Unilateral Renal Denervation. AB - Uninephrectomy (UniNX) in rats on a fixed food intake leads to increased lipolysis and a low-grade inflammation with an increased subset of circulating cytokines. Because UniNX ablates renal nerves on the side of the removed kidney, we tested the contribution of unilateral renal denervation in the phenotype of UniNX. We compared Sham-operated controls, left nephrectomy (UniNX) and unilateral left kidney denervation (uDNX) in rats 4 weeks after surgery. uDNX did not affect kidney weight and function. In general, the uDNX phenotype was similar to the UniNX phenotype especially for lipolysis in fat pads and increased low grade inflammation. uDNX led to decreased fat pad weight and increased hormone sensitive lipase and adipocyte triglyceride lipase mRNA levels in epididymal and inguinal adipose tissue, as well as increased circulating lipolysis markers beta hydroxybutyrate and glycerol. Measured circulating hormones such as leptin, T3 and insulin were similar amongst the three groups. The lipolytic cytokines interferon-gamma and granulocyte macrophage colony stimulating factor were increased in the circulation of both uDNX and UniNX groups. These two cytokines were also elevated in the spleen of both groups, but contrastingly they were decreased in fat pads, liver, and kidneys. Both uDNX and UniNX similarly increased noradrenaline content in fat pads and spleen. Melanocortin 4 receptor mRNA levels were increased in the brains of both uDNX and UniNX compared to Sham and may contribute to increased tissue noradrenaline levels. In addition, the farnesoid x receptor (FXR) may contribute to changes in tissue metabolism and inflammation, as anti-inflammatory FXR was decreased in the spleen but increased in other tissues in uDNX and UniNX compared to Sham. In summary, both uDNX and UniNX in rats promote metabolic and immunological alterations by mechanisms that seem to implicate modification of unilateral renal nerve pathways as well as central and peripheral neural pathways. PMID- 27378938 TI - Understanding the Cap Structure in K2P Channels. PMID- 27378940 TI - Psychophysical Differences in Ventilatory Awareness and Breathlessness between Athletes and Sedentary Individuals. AB - PURPOSE: Breathlessness is a complex set of symptoms that are comprised of both sensory and affective (emotional) dimensions. While ventilation is now understood to be a potential limiter to performance in highly-trained individuals, the contribution of breathlessness-anxiety in those nearing maximal ventilation during intense exercise has not yet been considered as a limiter to performance. METHODS: In this study, we compared the physiology and psychology of breathlessness in 20 endurance athletes with 20 untrained age- and sex-matched sedentary controls. Subjects completed baseline spirometry and anxiety questionnaires, an incremental exercise test to exhaustion and a steady-state hypercapnic ventilatory response test, with concurrent measures of breathlessness intensity and breathlessness-anxiety. RESULTS: Compared with sedentary subjects, athletes reported equivalent breathlessness intensity but greater breathlessness anxiety at maximal exercise (athletes vs. sedentary (mean +/- SD): breathlessness intensity (0-100%) 80.7 (22.7) vs. 72.5 (17.2), p = 0.21; breathlessness-anxiety (0-100%), 45.3 (36.3) vs. 22.3 (20.0), p = 0.02). Athletes operated at higher proportions of their maximal ventilatory capacity (MVV) (athletes vs. sedentary (mean ventilation +/- SD; % MVV): 101.6 (27.2) vs. 73.7 (30.1), p = 0.003). In the athletes there was a positive linear correlation between ventilation and breathlessness score during the hypercapnic challenge that was not observed in the sedentary controls. CONCLUSION: The results of this study indicate that whilst operating at high proportions of maximal ventilation, breathlessness anxiety becomes increasingly prominent in athletes. Our results suggest that ventilatory perception pathways may be a target for improved athletic performance in some individuals. PMID- 27378939 TI - Electrophysiological Mechanisms of Gastrointestinal Arrhythmogenesis: Lessons from the Heart. AB - Disruptions in the orderly activation and recovery of electrical excitation traveling through the heart and the gastrointestinal (GI) tract can lead to arrhythmogenesis. For example, cardiac arrhythmias predispose to thromboembolic events resulting in cerebrovascular accidents and myocardial infarction, and to sudden cardiac death. By contrast, arrhythmias in the GI tract are usually not life-threatening and much less well characterized. However, they have been implicated in the pathogenesis of a number of GI motility disorders, including gastroparesis, dyspepsia, irritable bowel syndrome, mesenteric ischaemia, Hirschsprung disease, slow transit constipation, all of which are associated with significant morbidity. Both cardiac and gastrointestinal arrhythmias can broadly be divided into non-reentrant and reentrant activity. The aim of this paper is to compare and contrast the mechanisms underlying arrhythmogenesis in both systems to provide insight into the pathogenesis of GI motility disorders and potential molecular targets for future therapy. PMID- 27378941 TI - Slower Lower Limb Blood Pooling Increases Orthostatic Tolerance in Women with Vasovagal Syncope. AB - BACKGROUND AND AIM: Slower lower limb blood pooling and associated blunted sympathetic activation has been detected in healthy women prone to orthostatic syncope. Whether these findings are true also for patients with vasovagal syncope (VVS) is unknown. The aim was to investigate initial blood pooling time (poolingtime, time to 50% of total blood pooling) together with hemodynamic responses and orthostatic tolerance during lower body negative pressure (LBNP) in VVS and healthy controls. METHODS AND RESULTS: Fourteen VVS women (25.7 +/- 1.3 years) and 15 healthy women (22.8 +/- 0.8 years) were subjected to single-step and graded LBNP to pre-syncope. Lower limb blood pooling (ml . 100 ml(-1)), poolingtime (s), hemodynamic responses and LBNP-tolerance were evaluated. LBNP induced comparable lower limb blood pooling in both groups (controls, 3.1 +/- 0.3; VVS, 2.9 +/- 0.3 ml . 100 ml(-1), P = 0.70). In controls, shorter poolingtime correlated to higher LBNP-tolerance (r = -0.550, P < 0.05) as well as better maintained stroke volume (r = -0.698, P < 0.01) and cardiac output (r = 0.563, P < 0.05). In contrast, shorter poolingtime correlated to lower LBNP tolerance in VVS (r = 0.821, P < 0.001) and larger decline in stroke volume (r = 0.611, P < 0.05). Furthermore, in controls, shorter poolingtime correlated to baroreflex-mediated hemodynamic changes during LBNP, e.g., increased vasoconstriction (P < 0.001). In VVS, poolingtime was not correlated with LBNP induced baroreceptor unloading, but rather highly correlated to resting calf blood flow (P < 0.001). CONCLUSIONS: Shorter poolingtime seems to elicit greater sympathetic activation with a concomitant higher orthostatic tolerance in healthy women. The contrasting findings in VVS indicate a deteriorated vascular sympathetic control suggesting well-defined differences already in the initial responses during orthostatic stress. PMID- 27378942 TI - Nitrate Intake Promotes Shift in Muscle Fiber Type Composition during Sprint Interval Training in Hypoxia. AB - PURPOSE: We investigated the effect of sprint interval training (SIT) in normoxia, vs. SIT in hypoxia alone or in conjunction with oral nitrate intake, on buffering capacity of homogenized muscle (betahm) and fiber type distribution, as well as on sprint and endurance performance. METHODS: Twenty-seven moderately trained participants were allocated to one of three experimental groups: SIT in normoxia (20.9% FiO2) + placebo (N), SIT in hypoxia (15% FiO2) + placebo (H), or SIT in hypoxia + nitrate supplementation (HN). All participated in 5 weeks of SIT on a cycle ergometer (30-s sprints interspersed by 4.5 min recovery-intervals, 3 weekly sessions, 4-6 sprints per session). Nitrate (6.45 mmol NaNO3) or placebo capsules were administered 3 h before each session. Before and after SIT participants performed an incremental VO2max-test, a 30-min simulated cycling time-trial, as well as a 30-s cycling sprint test. Muscle biopsies were taken from m. vastus lateralis. RESULTS: SIT decreased the proportion of type IIx muscle fibers in all groups (P < 0.05). The relative number of type IIa fibers increased (P < 0.05) in HN (P < 0.05 vs. H), but not in the other groups. SIT had no significant effect on betahm. Compared with H, SIT tended to enhance 30-s sprint performance more in HN than in H (P = 0.085). VO2max and 30-min time-trial performance increased in all groups to a similar extent. CONCLUSION: SIT in hypoxia combined with nitrate supplementation increases the proportion of type IIa fibers in muscle, which may be associated with enhanced performance in short maximal exercise. Compared with normoxic training, hypoxic SIT does not alter betahm or endurance and sprinting exercise performance. PMID- 27378943 TI - Copper Deficiency in the Lungs of TNF-alpha Transgenic Mice. AB - Tumor necrosis factor (TNF)-alpha is a well-known pro-inflammatory cytokine. Increased expression of Tnf-alpha is a feature of inflammatory lung diseases, such as asthma, emphysema, fibrosis, and smoking-induced chronic obstructive pulmonary disease (COPD). Using a mouse line with lung-specific Tnf-alpha overexpression (SPC-TNF-alpha) to mimic TNF-alpha-associated lung diseases, we investigated the role of chronic inflammation in the homeostasis of lung trace elements. We performed a quantitative survey of micronutrients and biometals, including copper (Cu), zinc (Zn), and selenium (Se), in the transgenic mice tissues. We also examined the expression of Cu-dependent proteins in the inflammatory lung tissue to determine whether they were affected by the severe Cu deficiency, including cuproenzymes, Cu transporters, and Cu chaperones. We found consistent lung-specific reduction of the metal Cu, with a mean decrease of 70%; however, Zn and Se were unaffected in all other tissues. RT-PCR showed that two Cu enzymes associated with lung pathology were downregulated: amine oxidase, Cu containing 3 (Aoc3) and lysyl oxidase (Lox). Two factors, vascular endothelial growth factor (Vegf) and focal adhesion kinase (Fak), related with Cu deficiency treatment, showed decreased expression in the transgenic inflammatory lung. We concluded that Cu deficiency occurs following chronic TNF-alpha-induced lung inflammation and this likely plays an essential role in the inflammation-induced lung damage. These results suggest the restoration of lung Cu status as a potential strategy in both treatment and prevention of chronic lung inflammation and related disorders. PMID- 27378944 TI - Cardiovascular Response Patterns to Sympathetic Stimulation by Central Hypovolemia. AB - In healthy subjects, variation in cardiovascular responses to sympathetic stimulation evoked by submaximal lower body negative pressure (LBNP) is considerable. This study addressed the question whether inter-subject variation in cardiovascular responses coincides with consistent and reproducible responses in an individual subject. In 10 healthy subjects (5 female, median age 22 years), continuous hemodynamic parameters (finger plethysmography; Nexfin, Edwards Lifesciences), and time-domain baroreflex sensitivity (BRS) were quantified during three consecutive 5-min runs of LBNP at -50 mmHg. The protocol was repeated after 1 week to establish intra-subject reproducibility. In response to LBNP, 5 subjects (3 females) showed a prominent increase in heart rate (HR; 54 +/ 14%, p = 0.001) with no change in total peripheral resistance (TPR; p = 0.25) whereas the other 5 subjects (2 females) demonstrated a significant rise in TPR (7 +/- 3%, p = 0.017) with a moderate increase in HR (21 +/- 9%, p = 0.004). These different reflex responses coincided with differences in resting BRS (22 +/ 8 vs. 11 +/- 3 ms/mmHg, p = 0.049) and resting HR (57 +/- 8 vs. 71 +/- 12 bpm, p = 0.047) and were highly reproducible over time. In conclusion, we found distinct cardiovascular response patterns to sympathetic stimulation by LBNP in young healthy individuals. These patterns of preferential autonomic blood pressure control appeared related to resting cardiac BRS and HR and were consistent over time. PMID- 27378945 TI - Coordinated Metabolic Changes and Modulation of Autophagy during Myogenesis. AB - Autophagy undergoes a fine tuning during tissue differentiation and organ remodeling in order to meet the dynamic changes in the metabolic needs. While the involvement of autophagy in the homeostasis of mature muscle tissues has been intensively studied, no study has so far addressed the regulation of autophagy in relation to the metabolic state during the myogenic differentiation. In our recently published study (Fortini et al., 2016) we investigated the metabolic profile and regulation of autophagy that accompany the differentiation process of mouse skeletal muscle satellite cells (MSC)-derived myoblasts into myotubes. Here, we briefly present these findings also in the light of similar studies conducted by other authors. We show that during myogenic differentiation mitochondrial function and activity are greatly increased, and the activation of autophagy accompanies the transition from myoblasts to myotube. Autophagy is mTORC1 inactivation-independent and, remarkably, is required to allow the myocyte fusion process, as shown by impaired cell fusion when the autophagic flux is inhibited either by genetic or drug manipulation. Further, we found that myoblasts derived from p53 null mice show defective terminal differentiation into myotubes and reduced activation of basal autophagy. Of note, glycolysis prevails and mitochondrial biogenesis is strongly impaired in p53-null myoblasts. Thus, autophagy, mitochondrial homeostasis, and differentiation are finely tuned in a coordinate manner during muscle biogenesis. PMID- 27378946 TI - Molecular and Functional Effects of a Splice Site Mutation in the MYL2 Gene Associated with Cardioskeletal Myopathy and Early Cardiac Death in Infants. AB - The homozygous appearance of the intronic mutation (IVS6-1) in the MYL2 gene encoding for myosin ventricular/slow-twitch skeletal regulatory light chain (RLC) was recently linked to the development of slow skeletal muscle fiber type I hypotrophy and early cardiac death. The IVS6-1 (c403-1G>C) mutation resulted from a cryptic splice site in MYL2 causing a frameshift and replacement of the last 32 codons by 19 different amino acids in the RLC mutant protein. Infants who were IVS6-1(+/+)-positive died between 4 and 6 months of age due to cardiomyopathy and heart failure. In this report we have investigated the molecular mechanism and functional consequences associated with the IVS6-1 mutation using recombinant human cardiac IVS6-1 and wild-type (WT) RLC proteins. Recombinant proteins were reconstituted into RLC-depleted porcine cardiac muscle preparations and subjected to enzymatic and functional assays. IVS6-1-RLC showed decreased binding to the myosin heavy chain (MHC) compared with WT, and IVS6-1-reconstituted myosin displayed reduced binding to actin in rigor. The IVS6-1 myosin demonstrated a significantly lower Vmax of the actin-activated myosin ATPase activity compared with WT. In stopped-flow experiments, IVS6-1 myosin showed slower kinetics of the ATP induced dissociation of the acto-myosin complex and a significantly reduced slope of the kobs-[MgATP] relationship compared to WT. In skinned porcine cardiac muscles, RLC-depleted and IVS6-1 reconstituted muscle strips displayed a significant decrease in maximal contractile force and a significantly increased Ca(2+) sensitivity, both hallmarks of hypertrophic cardiomyopathy-associated mutations in MYL2. Our results showed that the amino-acid changes in IVS6-1 were sufficient to impose significant conformational alterations in the RLC protein and trigger a series of abnormal protein-protein interactions in the cardiac muscle sarcomere. Notably, the mutation disrupted the RLC-MHC interaction and the steady-state and kinetics of the acto-myosin interaction. Specifically, slower myosin cross-bridge turnover rates and slower second-order MgATP binding rates of acto-myosin interactions were observed in IVS6-1 vs. WT reconstituted cardiac preparations. Our in vitro results suggest that when placed in vivo, IVS6-1 may lead to cardiomyopathy and early death of homozygous infants by severely compromising the ability of myosin to develop contractile force and maintain normal systolic and diastolic cardiac function. PMID- 27378947 TI - Exercise, Nrf2 and Antioxidant Signaling in Cardiac Aging. AB - Aging is represented by a progressive decline in cellular functions. The age related deformities in cardiac behaviors are the loss of cardiac myocytes through apoptosis or programmed cell death. Oxidative stress (OS) and its deleterious consequence contribute to age-related mechanical remodeling, reduced regenerative capacity, and apoptosis in cardiac tissue. The pathogenesis of OS in the elderly can predispose the heart to other cardiac complications such as atherosclerosis, hypertension, ischemic heart disease, cardiac myopathy, and so on. At the molecular level, oxidant-induced activation of Nrf2 (Nuclear erythroid-2-p45 related factor-2), a transcription factor, regulates several genes containing AREs (Antioxidant Response Element) and bring the respective translates to counteract the reactive radicals and establish homeostasis. Myriad of Nrf2 gene knockout studies in various organs such as lung, liver, kidney, brain, etc. have shown that dysregulation of Nrf2 severely affects the oxidant/ROS sensitivity and predispose the system to several pathological changes with aberrant cellular lesions. On the other hand, its gain of function chemical interventions exhibited oxidant stress resistance and cytoprotection. However, thus far, only a few investigations have shown the potential role of Nrf2 and its non-pharmacological induction in cardiac aging. Therefore, here we review the involvement of Nrf2 signaling along with its responses and ramifications on the cascade of OS under acute exercise stress (AES), moderate exercise training (MET), and endurance exercise stress (EES) conditions in the aging heart. PMID- 27378948 TI - Lower Arm Muscle Activation during Indirect-Localized Vibration: The Influence of Skill Levels When Applying Different Acceleration Loads. AB - We investigated the electromyographic response to synchronous indirect-localized vibration interventions in international and national table tennis players. Twenty-six male table tennis players, in a standing position, underwent firstly an upper arms maximal voluntary contraction and thereafter two different 30-s vibration interventions in random order: high acceleration load (peak acceleration = 12.8 g, frequency = 40 Hz; peak-to-peak displacement = 4.0 mm), and low acceleration load (peak acceleration = 7.2 g, frequency = 30 Hz, peak-to peak displacement = 4.0 mm). Surface electromyography root mean square from brachioradialis, extensor digitorum, flexor carpi radialis, and flexor digitorum superficialis recorded during the two vibration interventions was normalized to the maximal voluntary contraction recording. Normalized surface electromyography root mean square was higher in international table tennis players with respect to national ones in all the interactions between muscles and vibration conditions (P < 0.05), with the exception of flexor carpi radialis (at low acceleration load, P > 0.05). The difference in normalized surface electromyography root mean square between international table tennis players and national ones increased in all the muscles with high acceleration load (P < 0.05), with the exception of flexor digitorum superficialis (P > 0.05). The muscle activation during indirect localized vibration seems to be both skill level and muscle dependent. These results can optimize the training intervention in table tennis players when applying indirect-localized vibration to lower arm muscles. Future investigations should discriminate between middle- and long-term adaptations in response to specific vibration loads. PMID- 27378950 TI - Outpatient Psychotherapy Reduces Health-Care Costs: A Study of 22,294 Insurants over 5 Years. AB - BACKGROUND: The project "Quality Assurance in Ambulatory Psychotherapy in Bavaria" (QS-PSY-BAY) focuses on the quality assurance of outpatient psychotherapy (OPT) in Germany in terms of symptom reduction and cost reduction under naturalistic conditions. In this study, we examined the effectiveness of psychotherapy in terms of pre-post cost reduction. METHOD: The health-care costs of N = 22,294 insurants over a 5-year period were examined in a naturalistic longitudinal design. Six participating health insurance funds provided data on costs related to inpatient treatment, outpatient treatment, drugs, and hospitalization and work disability days. RESULTS: We found that the average annual total costs for inpatient and outpatient treatments as well as drug costs and work disability days increased from the second to the first year before OPT. Besides a large and significant reduction of work disability days (41.8%), hospitalization days (27.4%), and inpatient costs (21.5%) from the first year before versus the first year following OPT, we found evidence for long-term effects: the number of work disability days in the second year after OPT was lower (23.8%), and drug costs were higher than in the second year before OPT (41.5%). CONCLUSION: We conclude that OPT as a part of the health insurance system is an investment which can pay off in the future especially in terms of lower inpatient costs and work disability. PMID- 27378951 TI - Effectiveness of In Virtuo Exposure and Response Prevention Treatment Using Cognitive-Behavioral Therapy for Obsessive-Compulsive Disorder: A Study Based on a Single-Case Study Protocol. AB - Obsessive-compulsive disorder (OCD) is characterized by the presence of distressing, recurrent and intrusive thoughts, impulses, or doubts as well as behavioral or mental rituals. OCD has various subtypes, including the fear of contamination in which individuals fear bacteria, germs, disease, or bodily secretions, and engage in clinically significant cleaning and avoidance rituals. Cognitive-behavioral therapy (CBT) is an effective treatment for OCD and involves, among other therapeutic strategies, exposing patients to feared stimuli while preventing them to engage in compulsive behaviors. In recent years, virtual reality (VR) has shown the potential of in virtuo exposure with people suffering from anxiety disorders and OCD. The objective of this pilot study is to examine the effectiveness of a CBT program where exposure in conducted in virtuo. Three adults suffering from OCD with a dominant subtype of contamination were enrolled in a single-case design with multiple baselines across participants. The presence and intensity of obsessions and compulsions were assessed daily during baselines of 3-, 4-, or 5-week, and a 12-session treatment. Follow-up information was gathered after 4 and 8 months. Treatment outcome is assessed with visual inspection of the graphs and ARMA time-series analyses. Clinical information, self-reports, and details of the treatment are provided for each patient. Statistical analyses for the time-series data revealed a statistically significant improvement in all three participants, but global improvement is considered positive for only two. This study innovates in proving preliminary support for the usefulness of VR in the CBT of OCD with contamination features. PMID- 27378949 TI - Updates and Current Perspectives of Psychiatric Assessments after Traumatic Brain Injury: A Systematic Review. AB - Neuropsychological and psychiatric disorders represent a major concern and cause of disabilities after the trauma, contributing to worse recovery after traumatic brain injury (TBI). However, the lack of well-defined parameters to evaluate patient's psychiatric disorders leads to a wide range of diagnoses and symptoms. The aim of this study was to perform a review of literature in order to gather data of the most common scales and inventories used to assess and diagnose depression, anxiety, and posttraumatic stress disorder (PTSD) after TBI. We conducted a literature search via MEDLINE, PubMed, and Web of Science. We included reviews, systematic reviews, and meta-analysis studies, and we used the following keywords: "traumatic brain injury OR TBI," "depression OR depressive disorder," "anxiety," and "posttraumatic stress disorder OR PTSD." From 610 titles, a total of 68 systematic reviews or meta-analysis were included in the section "Results" of this review: depression (n = 32), anxiety (n = 9), and PTSD (n = 27). Depression after TBI is a more established condition, with more homogeneous studies. Anxiety and PTSD disorders have been studied in a heterogeneous way, usually as comorbidity with other psychiatric disorders. Some scales and inventories designed for the general community may not be appropriate for patients with TBI. PMID- 27378952 TI - Reward Learning, Neurocognition, Social Cognition, and Symptomatology in Psychosis. AB - BACKGROUND: Patients with psychosis spectrum disorders exhibit deficits in social and neurocognition, as well as hallmark abnormalities in motivation and reward processing. Aspects of reward processing may overlap behaviorally and neurobiologically with some elements of cognitive functioning, and abnormalities in these processes may share partially overlapping etiologies in patients. However, whether reward processing and cognition are associated across the psychoses and linked to state and trait clinical symptomatology is unclear. METHOD: The present study examined associations between cognitive functioning, reward learning, and clinical symptomatology in a cross-diagnostic sample. Patients with schizophrenia (SZ; n = 37), bipolar I disorder with psychosis (BD; n = 42), and healthy controls (n = 29) were assessed for clinical symptoms (patients only), neurocognitive functioning using the MATRICS Battery (MCCB) and reward learning using the probabilistic reward task (PRT). Groups were compared on neurocognition and PRT response bias, and associations between PRT response bias and neurocognition or clinical symptoms were examined controlling for demographic variables and PRT task difficulty (discriminability). RESULTS: Patients with SZ performed worse than controls on most measures of neurocognition; patients with BD exhibited deficits in some domains between the level of patients with SZ and controls. The SZ - but not BD - group exhibited deficits in social cognition compared to controls. Patients and controls did not differ on PRT response bias, but did differ on PRT discriminability. Better response bias across the sample was associated with poorer social cognition, but not neurocognition; conversely, discriminability was associated with neurocognition but not social cognition. Symptoms of psychosis, particularly negative symptoms, were associated with poorer response bias across patient groups. DISCUSSION: Reward learning was associated with symptoms of psychosis - in particular negative symptoms - across diagnoses, and was predictive of worse social cognition. Reward learning was not associated with neurocognitive performance, suggesting that, across patient groups, social cognition but not neurocognition may share common pathways with this aspect of reinforcement learning. Better understanding of how cognitive dysfunction and reward processing deficits relate to one another, to other key symptom dimensions (e.g., psychosis), and to diagnostic categories, may help clarify shared etiological pathways and guide efforts toward targeted treatment approaches. PMID- 27378953 TI - Neuroinflammation and Behavior in HIV-1 Transgenic Rats Exposed to Chronic Adolescent Stress. AB - Highly active antiretroviral therapy (HAART) has improved prognosis for people living with HIV (PLWH) and dramatically reduced the incidence of AIDS. However, even when viral load is controlled, PLWH develop psychiatric and neurological disorders more frequently than those living without HIV. Adolescents with HIV are particularly susceptible to the development of psychiatric illnesses and neurocognitive impairments. While both psychiatric and neurocognitive disorders have been found to be exacerbated by stress, the extent to which chronic stress and HIV-1 viral proteins interact to impact behavior and relevant neuroinflammatory processes is unknown. Determination of the individual contributions of stress and HIV to neuropsychiatric disorders is heavily confounded in humans. In order to isolate the influence of HIV-1 proteins and chronic stress on behavior and neuroinflammation, we employed the HIV-1 transgenic (Tg) rat model, which expresses HIV-1 proteins with a gag and pol deletion, allowing for viral protein expression without viral replication. This Tg line has been characterized as a model of HAART-controlled HIV-1 infection due to the lack of viral replication but continued presence of HIV-1 proteins. We exposed male and female adolescent HIV-1 Tg rats to a mixed-modality chronic stress paradigm consisting of isolation, social defeat and restraint, and assessed behavior, cerebral vascularization, and neuroinflammatory endpoints. Stress, sex, and presence of the HIV-1 transgene impacted weight gain in adolescent rats. Female HIV-1 Tg rats showed decreases in central tendency during the light cycle in the open field regardless of stress exposure. Both male and female HIV-1 Tg rats exhibited decreased investigative behavior in the novel object recognition task, but no memory impairments. Adolescent stress had no effect on the tested behaviors. Microglia in female HIV-1 Tg rats exhibited a hyper-ramified structure, and gene expression of complement factor B was increased in the hippocampus. In addition, adolescent stress exposure increased microglial branching and junctions in female wild-type rats without causing any additional increase in HIV-1 rats. These data suggest that the presence of HIV-1 proteins during development leads to alterations in behavioral and neuroinflammatory endpoints that are not further impacted by concurrent chronic adolescent stress. PMID- 27378954 TI - The Impact of Target Frequency on Intra-Individual Variability in Euthymic Bipolar Disorder: A Comparison of Two Sustained Attention Tasks. AB - Greater intra-individual variability (IIV) in reaction time (RT) on a sustained attention task has been reported in patients with bipolar disorder (BD) compared with healthy controls. However, it is unclear whether IIV is task specific, or whether it represents general cross-task impairment in BD. This study aimed to investigate whether IIV occurs in sustained attention tasks with different parameters. Twenty-two patients with BD (currently euthymic) and 17 controls completed two sustained attention tasks on different occasions: a low target frequency (~20%) Vigil continuous performance test (CPT) and a high target frequency (~70%) CPT version A-X (CPT-AX). Variability measures (individual standard deviation and coefficient of variation) were calculated per participant, and ex-Gaussian modeling was also applied. This was supplemented by Vincentile analysis to characterize RT distributions. Results indicated that participants (patients and controls) were generally slower and more variable when completing the Vigil CPT compared with CPT-AX. Significant group differences were also observed in the Vigil CPT, with euthymic BD patients being more variable than controls. This result suggests that IIV in BD demonstrates some degree of task specificity. Further research should incorporate analysis of additional RT distributional models (drift diffusion and fast Fourier transform) to fully characterize the pattern of IIV in BD, as well as its relationship to cognitive processes. PMID- 27378956 TI - Mental Pain and Suicide: A Systematic Review of the Literature. AB - BACKGROUND: Mental pain, defined as a subjective experience characterized by perception of strong negative feelings and changes in the self and its function, is no less real than other types of grief. Mental pain has been considered to be a distinct entity from depression. We have performed a systematic review analyzing the relationship between mental pain and suicide by providing a qualitative data synthesis of the studies. METHODS: We have conducted, in accordance with PRISMA guidelines, a systematic search for the literature in PubMed, Web Of Science, and Scopus. Search terms were "mental pain" "OR" "psychological pain" OR "psychache" combined with the Boolean "AND" operator with "suicid*." In addition, a manual search of the literature, only including the term "psychache," was performed on Google Scholar for further studies not yet identified. RESULTS: Initial search identified 1450 citations. A total of 42 research reports met the predefined inclusion criteria and were analyzed. Mental pain was found to be a significant predictive factor of suicide risk, even in the absence of a diagnosed mental disorder. Specifically, mental pain is a stronger factor of vulnerability of suicidal ideation than depression. CONCLUSION: Mental pain is a core clinical factor for understanding suicide, both in the context of mood disorders and independently from depression. Health care professionals need to be aware of the higher suicidal risk in patients reporting mental pain. In this regard, psychological assessment should include a clinimetric evaluation of mental pain in order to further detect its contribution to suicidal tendency. PMID- 27378957 TI - Clinical Characteristics Associated with Suicide Attempts in Clinical Settings: A Comparison of Suicidal and Non-Suicidal Depressed Inpatients. AB - INTRODUCTION: Both psychiatrists and psychiatric nurses are involved in the psychiatric management of suicidal inpatients. One-to-one observation by qualified nurses and the accommodation of the patient in a room close to the infirmary are usually recommended. Suicidal risk should be reassessed periodically to check response to treatment. AIM: To compare the severity of depressive symptoms in depressed inpatients admitted after an attempted suicide and those admitted for any other reason and to assess the severity of suicide attempts and the management of suicidal risk in clinical settings. MATERIALS AND METHODS: We divided the sample into two subgroups: patients with a diagnosis of depression admitted because of a recent suicide attempt and depressed patients with no recent history of attempted suicide. Socio-demographic and clinical data were gathered; assessments included the Montgomery-Asberg Depression Rating Scale and the Nurses' Global Assessment of Suicide Risk (NGASR). RESULTS: Forty-six patients were recruited over a 1-year period: 20 were admitted to the hospital following a suicide attempt; the other 26 had not attempted suicide and were admitted for other depression-related reasons. Multivariate analysis revealed a correlation between use of antidepressants and recent attempted suicide. Attempting suicide was not related to the severity of depressive symptoms. In the recent suicide attempt subgroup, NGASR suicide risk levels were lower at discharge than at admission. Patients with a recent history of attempted suicide had a higher number of suicide attempts in their clinical history than patients with no recent history of attempted suicide. CONCLUSION: There were no correlations between psychiatric diagnosis, severity of depressive symptoms, and recent suicide attempt. Antidepressant therapy protected against suicide attempts. History of suicide attempts was one of the best predictors of recent attempted suicide. A more thorough understanding of the complex phenomenon of suicide and the reasons for suicidal behavior is needed. PMID- 27378955 TI - Can Bayesian Theories of Autism Spectrum Disorder Help Improve Clinical Practice? AB - Diagnosis and individualized treatment of autism spectrum disorder (ASD) represent major problems for contemporary psychiatry. Tackling these problems requires guidance by a pathophysiological theory. In this paper, we consider recent theories that re-conceptualize ASD from a "Bayesian brain" perspective, which posit that the core abnormality of ASD resides in perceptual aberrations due to a disbalance in the precision of prediction errors (sensory noise) relative to the precision of predictions (prior beliefs). This results in percepts that are dominated by sensory inputs and less guided by top-down regularization and shifts the perceptual focus to detailed aspects of the environment with difficulties in extracting meaning. While these Bayesian theories have inspired ongoing empirical studies, their clinical implications have not yet been carved out. Here, we consider how this Bayesian perspective on disease mechanisms in ASD might contribute to improving clinical care for affected individuals. Specifically, we describe a computational strategy, based on generative (e.g., hierarchical Bayesian) models of behavioral and functional neuroimaging data, for establishing diagnostic tests. These tests could provide estimates of specific cognitive processes underlying ASD and delineate pathophysiological mechanisms with concrete treatment targets. Written with a clinical audience in mind, this article outlines how the development of computational diagnostics applicable to behavioral and functional neuroimaging data in routine clinical practice could not only fundamentally alter our concept of ASD but eventually also transform the clinical management of this disorder. PMID- 27378958 TI - Editorial: Frontiers in Synaptic Plasticity: Dendritic Spines, Circuitries and Behavior. PMID- 27378959 TI - The Construction of Impossibility: A Logic-Based Analysis of Conjuring Tricks. AB - Psychologists and cognitive scientists have long drawn insights and evidence from stage magic about human perceptual and attentional errors. We present a complementary analysis of conjuring tricks that seeks to understand the experience of impossibility that they produce. Our account is first motivated by insights about the constructional aspects of conjuring drawn from magicians' instructional texts. A view is then presented of the logical nature of impossibility as an unresolvable contradiction between a perception-supported belief about a situation and a memory-supported expectation. We argue that this condition of impossibility is constructed not simply through misperceptions and misattentions, but rather it is an outcome of a trick's whole structure of events. This structure is conceptualized as two parallel event sequences: an effect sequence that the spectator is intended to believe; and a method sequence that the magician understands as happening. We illustrate the value of this approach through an analysis of a simple close-up trick, Martin Gardner's Turnabout. A formalism called propositional dynamic logic is used to describe some of its logical aspects. This elucidates the nature and importance of the relationship between a trick's effect sequence and its method sequence, characterized by the careful arrangement of four evidence relationships: similarity, perceptual equivalence, structural equivalence, and congruence. The analysis further identifies two characteristics of magical apparatus that enable the construction of apparent impossibility: substitutable elements and stable occlusion. PMID- 27378960 TI - The Importance of Formalizing Computational Models of Face Adaptation Aftereffects. AB - Face adaptation is widely used as a means to probe the neural representations that support face recognition. While the theories that relate face adaptation to behavioral aftereffects may seem conceptually simple, our work has shown that testing computational instantiations of these theories can lead to unexpected results. Instantiating a model of face adaptation not only requires specifying how faces are represented and how adaptation shapes those representations but also specifying how decisions are made, translating hidden representational states into observed responses. Considering the high-dimensionality of face representations, the parallel activation of multiple representations, and the non linearity of activation functions and decision mechanisms, intuitions alone are unlikely to succeed. If the goal is to understand mechanism, not simply to examine the boundaries of a behavioral phenomenon or correlate behavior with brain activity, then formal computational modeling must be a component of theory testing. To illustrate, we highlight our recent computational modeling of face adaptation aftereffects and discuss how models can be used to understand the mechanisms by which faces are recognized. PMID- 27378961 TI - Are Individual Differences in Arithmetic Fact Retrieval in Children Related to Inhibition? AB - Although it has been proposed that inhibition is related to individual differences in mathematical achievement, it is not clear how it is related to specific aspects of mathematical skills, such as arithmetic fact retrieval. The present study therefore investigated the association between inhibition and arithmetic fact retrieval and further examined the unique role of inhibition in individual differences in arithmetic fact retrieval, in addition to numerical magnitude processing. We administered measures of cognitive inhibition (i.e., numerical and non-numerical stroop tasks) and a complementary, more ecologically valid measure of children's inhibition in the classroom (i.e., teacher questionnaire), as well as numerical magnitude processing (i.e., symbolic and non symbolic numerical magnitude comparison) and arithmetic fact retrieval (i.e., two verification tasks) in 86 typically developing third graders. We used a correlation, a regression and a Bayesian analysis. This study failed to observe a significant association between inhibition and arithmetic fact retrieval. Consequently, our results did not reveal a unique contribution of inhibition to arithmetic fact retrieval in addition to numerical magnitude processing. On the other hand, symbolic numerical magnitude processing turned out to be a very powerful predictor of arithmetic fact retrieval, as indicated by both frequentist and Bayesian approaches. PMID- 27378962 TI - Distinct Visual Processing of Real Objects and Pictures of Those Objects in 7- to 9-month-old Infants. AB - The present study examined 7- and 9-month-old infants' visual habituation to real objects and pictures of the same objects and their preferences between real and pictorial versions of the same objects following habituation. Different hypotheses would predict that infants may habituate faster to pictures than real objects (based on proposed theoretical links between behavioral habituation in infants and neuroimaging adaptation in adults) or to real objects vs. pictures (based on past infant electrophysiology data). Sixty-one 7-month-old infants and fifty-nine 9-month-old infants were habituated to either a real object or a picture of the same object and afterward preference tested with the habituation object paired with either the novel real object or its picture counterpart. Infants of both age groups showed basic information-processing advantages for real objects. Specifically, during the initial presentations, 9-month-old infants looked longer at stimuli in both formats than the 7-month olds but more importantly both age groups looked longer at real objects than pictures, though with repeated presentations, they habituated faster for real objects such that at the end of habituation, they looked equally at both types of stimuli. Surprisingly, even after habituation, infants preferred to look at the real objects, regardless of whether they had habituated to photos or real objects. Our findings suggest that from as early as 7-months of age, infants show strong preferences for real objects, perhaps because real objects are visually richer and/or enable the potential for genuine interactions. PMID- 27378963 TI - Smartphone Applications Utilizing Biofeedback Can Aid Stress Reduction. AB - INTRODUCTION: Stress is one of the leading global causes of disease and premature mortality. Despite this, interventions aimed at reducing stress have low adherence rates. The proliferation of mobile phone devices along with gaming style applications allows for a unique opportunity to broaden the reach and appeal of stress-reduction interventions in modern society. We assessed the effectiveness of two smartphone applications games combined with biofeedback in reducing stress. METHODS: We compared a control game to gaming-style smartphone applications combined with a skin conductance biofeedback device (the Pip). Fifty participants aged between 18 and 35 completed the Trier Social Stress Test. They were then randomly assigned to the intervention (biofeedback game) or control group (a non-biofeedback game) for thirty minutes. Perceived stress, heart rate and mood were measured before and after participants had played the games. RESULTS: A mixed factorial ANOVA showed a significant interaction between time and game type in predicting perceived stress [F(1,48) = 14.19, p < 0.001]. Participants in the biofeedback intervention had significantly reduced stress compared to the control group. There was also a significant interaction between time and game in predicting heart rate [F(1,48) = 6.41, p < 0.05]. Participants in the biofeedback intervention showed significant reductions in heart rate compared to the control group. DISCUSSION: This illustrates the potential for gaming-style smartphone applications combined with biofeedback as stress reduction interventions. PMID- 27378964 TI - Dance Movements Enhance Song Learning in Deaf Children with Cochlear Implants. AB - Music perception of cochlear implants (CI) users is constrained by the absence of salient musical pitch cues crucial for melody identification, but is made possible by timing cues that are largely preserved by current devices. While musical timing cues, including beats and rhythms, are a potential route to music learning, it is not known what extent they are perceptible to CI users in complex sound scenes, especially when pitch and timbral features can co-occur and obscure these musical features. The task at hand, then, becomes one of optimizing the available timing cues for young CI users by exploring ways that they might be perceived and encoded simultaneously across multiple modalities. Accordingly, we examined whether training tasks that engage active music listening through dance might enhance the song identification skills of deaf children with CIs. Nine CI children learned new songs in two training conditions: (a) listening only (auditory learning), and (2) listening and dancing (auditory-motor learning). We examined children's ability to identify original song excerpts, as well as mistuned, and piano versions from a closed-set task. While CI children were less accurate than their normal hearing peers, they showed greater song identification accuracies in versions that preserved the original instrumental beats following learning that engaged active listening with dance. The observed performance advantage is further qualified by a medium effect size, indicating that the gains afforded by auditory-motor learning are practically meaningful. Furthermore, kinematic analyses of body movements showed that CI children synchronized to temporal structures in music in a manner that was comparable to normal hearing age-matched peers. Our findings are the first to indicate that input from CI devices enables good auditory-motor integration of timing cues in child CI users for the purposes of listening and dancing to music. Beyond the heightened arousal from active engagement with music, our findings indicate that a more robust representation or memory of musical timing features was made possible by multimodal processing. Methods that encourage CI children to entrain, or track musical timing with body movements, may be particularly effective in consolidating musical knowledge than methods that engage listening only. PMID- 27378965 TI - A Novel Technique for Improving Bodily Experience in a Non-operable Super-Super Obesity Case. AB - INTRODUCTION: The available clinical guidelines for super-super obese patients (i.e., with body mass index (BMI) > 60 kg/m(2)) that are not suitable for bariatric surgery mandate a palliative multidisciplinary treatment (i.e., production and maintenance of weight loss) provided in a center of excellence. However, the modality and the impact of this approach are still controversial. Moreover, it is not able to address the high level of body dissatisfaction and body distortions that are common among these patients. CLINICAL PRESENTATION: We report the case of a non-operable super-super obesity - a 37 year old woman with a BMI of 62 kg/m(2) - receiving a specialized treatment for her obstructive sleep apnea. She entered a multidisciplinary program that promoted healthy behaviors, including physical activities and psychological intervention. To improve body dissatisfaction, which was linked to a significant multisensory impairment of body perception, she also entered a virtual reality (VR) body-swapping illusion protocol. At the end of the current investigation, the patient continued her multidisciplinary program, reporting an increase in the motivation for undertaking healthy behavior and a decrease in the anxiety feelings associated with her clinical condition. CONCLUSION: This case provides preliminary evidence that both body dissatisfaction and body-size distortions of non-operable super super obesity patients could be addressed by a VR body-swapping protocol, which is important because the palliative multidisciplinary treatment recommended for these patients is not able to address them. Interestingly, the use of a VR body swapping illusion protocol seems to be able to improve not only the experience of the body in these patients but their motivation for change, too. PMID- 27378966 TI - Greater Emotional Gain from Giving in Older Adults: Age-Related Positivity Bias in Charitable Giving. AB - Older adults have been shown to avoid negative and prefer positive information to a higher extent than younger adults. This positivity bias influences their information processing as well as decision-making. We investigate age-related positivity bias in charitable giving in two studies. In Study 1 we examine motivational factors in monetary donations, while Study 2 focuses on the emotional effect of actual monetary donations. In Study 1, participants (n = 353, age range 20-74 years) were asked to rate their affect toward a person in need and then state how much money they would be willing to donate to help this person. In Study 2, participants (n = 108, age range 19-89) were asked to rate their affect toward a donation made a few days prior. Regression analysis was used to investigate whether or not the positivity bias influences the relationship between affect and donations. In Study 1, we found that older adults felt more sympathy and compassion and were less motivated by negative affect when compared to younger adults, who were motivated by both negative and positive affect. In Study 2, we found that the level of positive emotional reactions from monetary donations was higher in older participants compared to younger participants. We find support for an age-related positivity bias in charitable giving. This is true for motivation to make a future donation, as well as affective thinking about a previous donation. We conclude that older adults draw more positive affect from both the planning and outcome of monetary donations and hence benefit more from engaging in monetary charity than their younger counterparts. PMID- 27378967 TI - Is Anorexia Nervosa a Disorder of the Self? A Psychological Approach. AB - The debate concerning the pathogenesis and the maintaining factors of eating disorders, anorexia nervosa in particular, is ongoing especially since therapeutic interventions do not result in satisfactory and enduring rates of remission. This paper presents a model for the pathogenesis of eating disorders, based on the hypothesis of a deficiency in the development of the self. We present the theory in light of new evidence concerning the role of attachment insecurity in the development and maintenance of eating disorders. In particular, we define the self in eating disorders in a comprehensive way by taking into account recent evidence from experimental psychology and neurobiology. The paper considers the development of the self in terms of its synchronic (i.e., experienced in the moment) and diachronic (i.e., experienced as continuous over time) aspects. Both synchronic and diachronic aspects of the self are relevant to the expression of eating disorder symptoms. Further, the maturation of the self is interwoven with the development of attachment functioning from infancy to adolescence. This interplay between these developmental processes of the self and of attachment could be crucial in understanding the pathogenesis of eating disorders. The final part of the paper suggests a neurobiological link between the theory of the self in the eating disorders and the spatiotemporal functioning of the brain. Disturbances in spatiotemporal functioning may represent the neurobiological pathway by which deficiencies in the self is related to attachment functions in individuals with eating disorders. PMID- 27378969 TI - Asynchronous Video Interviewing as a New Technology in Personnel Selection: The Applicant's Point of View. AB - The present study aimed to integrate findings from technology acceptance research with research on applicant reactions to new technology for the emerging selection procedure of asynchronous video interviewing. One hundred six volunteers experienced asynchronous video interviewing and filled out several questionnaires including one on the applicants' personalities. In line with previous technology acceptance research, the data revealed that perceived usefulness and perceived ease of use predicted attitudes toward asynchronous video interviewing. Furthermore, openness revealed to moderate the relation between perceived usefulness and attitudes toward this particular selection technology. No significant effects emerged for computer self-efficacy, job interview self efficacy, extraversion, neuroticism, and conscientiousness. Theoretical and practical implications are discussed. PMID- 27378968 TI - Synchrony in Psychotherapy: A Review and an Integrative Framework for the Therapeutic Alliance. AB - During psychotherapy, patient and therapist tend to spontaneously synchronize their vocal pitch, bodily movements, and even their physiological processes. In the present article, we consider how this pervasive phenomenon may shed new light on the therapeutic relationship- or alliance- and its role within psychotherapy. We first review clinical research on the alliance and the multidisciplinary area of interpersonal synchrony. We then integrate both literatures in the Interpersonal Synchrony (In-Sync) model of psychotherapy. According to the model, the alliance is grounded in the coupling of patient and therapist's brains. Because brains do not interact directly, movement synchrony may help to establish inter-brain coupling. Inter-brain coupling may provide patient and therapist with access to another's internal states, which facilitates common understanding and emotional sharing. Over time, these interpersonal exchanges may improve patients' emotion-regulatory capacities and related therapeutic outcomes. We discuss the empirical assessment of interpersonal synchrony and review preliminary research on synchrony in psychotherapy. Finally, we summarize our main conclusions and consider the broader implications of viewing psychotherapy as the product of two interacting brains. PMID- 27378970 TI - Effect of Partnership Status on Preferences for Facial Self-Resemblance. AB - Self-resemblance has been found to have a context-dependent effect when expressing preferences for faces. Whereas dissimilarity preference during mate choice in animals is often explained as an evolutionary adaptation to increase heterozygosity of offspring, self-resemblance can be also favored in humans, reflecting, e.g., preference for kinship cues. We performed two studies, using transformations of facial photographs to manipulate levels of resemblance with the rater, to examine the influence of self-resemblance in single vs. coupled individuals. Raters assessed facial attractiveness of other-sex and same-sex photographs according to both short-term and long-term relationship contexts. We found a preference for dissimilarity of other-sex and same-sex faces in single individuals, but no effect of self-resemblance in coupled raters. No effect of sex of participant or short-term vs. long-term attractiveness rating was observed. The results support the evolutionary interpretation that dissimilarity of other-sex faces is preferred by uncoupled individuals as an adaptive mechanism to avoid inbreeding. In contrast, lower dissimilarity preference of other-sex faces in coupled individuals may reflect suppressed attention to attractiveness cues in potential alternative partners as a relationship maintenance mechanism, and its substitution by attention to cues of kinship and psychological similarity connected with greater likelihood of prosocial behavior acquisition from such persons. PMID- 27378971 TI - Reminiscence through the Lens of Social Media. AB - Reminiscence is used to support and create new social bonds and give meaning to life. Originally perceived as a preoccupation of the aged, we now recognize that reminiscence has value throughout the lifespan. Increasingly, social media can be used to both support and prompt reminiscence, with Facebook's Lookback or Year in Review as recent examples. This work takes prompted reminiscence further, asking what forms and functions of reminiscence are supported by social media. Utilizing the online service MySocialBook, we invited participants to curate content from their personal Facebook account to then be transformed into a printed book. We used that book as a prompt for discussion of the reminiscence function of the curated material, using Westerhof and Bohlmeijer's (2014) reminiscence framework as a starting point. We conclude that this framework is valuable in understanding the role of social media in reminiscence, but note that earlier models, such as Webster's Reminiscence Functions Scale, are also relevant. We contribute to the reminiscence debate by adding a technological lens to the process of life review, whilst concurring with other researchers in this field that a robust conceptual framework is lacking, particularly when considering the forms of reminiscence that are most salient for younger people. PMID- 27378972 TI - The ADHD Concomitant Difficulties Scale (ADHD-CDS), a Brief Scale to Measure Comorbidity Associated to ADHD. AB - INTRODUCTION: Although the critical feature of attention-deficit/hyperactivity disorder (ADHD) is a persistent pattern of inattention and/or hyperactivity/impulsivity behavior, the disorder is clinically heterogeneous, and concomitant difficulties are common. Children with ADHD are at increased risk for experiencing lifelong impairments in multiple domains of daily functioning. In the present study we aimed to build a brief ADHD impairment-related tool -ADHD concomitant difficulties scale (ADHD-CDS)- to assess the presence of some of the most important comorbidities that usually appear associated with ADHD such as emotional/motivational management, fine motor coordination, problem solving/management of time, disruptive behavior, sleep habits, academic achievement and quality of life. The two main objectives of the study were (i) to discriminate those profiles with several and important ADHD functional difficulties and (ii) to create a brief clinical tool that fosters a comprehensive evaluation process and can be easily used by clinicians. METHODS: The total sample included 399 parents of children with ADHD aged 6-18 years (M = 11.65; SD = 3.1; 280 males) and 297 parents of children without a diagnosis of ADHD (M = 10.91; SD = 3.2; 149 male). The scale construction followed an item improved sequential process. RESULTS: Factor analysis showed a 13-item single factor model with good fit indices. Higher scores on inattention predicted higher scores on ADHD-CDS for both the clinical sample (beta = 0.50; p < 0.001) and the whole sample (beta = 0.85; p < 0.001). The ROC curve for the ADHD-CDS (against the ADHD diagnostic status) gave an area under the curve (AUC) of.979 (95%, CI = [0.969, 0.990]). DISCUSSION: The ADHD-CDS has shown preliminary adequate psychometric properties, with high convergent validity and good sensitivity for different ADHD profiles, which makes it a potentially appropriate and brief instrument that may be easily used by clinicians, researchers, and health professionals in dealing with ADHD. PMID- 27378973 TI - "Letting Go" (Implicitly): Priming Mindfulness Mitigates the Effects of a Moderate Social Stressor. AB - This experimental study investigated whether implicitly priming mindfulness would facilitate psychological and cortisol recovery after undergoing a standardized psychological stressor. After completing baseline measures of well-being, all participants (N = 91) completed a public speaking stress task, were implicitly primed with "mindfulness" or "neutral" concepts using a scrambled sentence task, and finally, reported their situational well-being and provided cortisol samples. Simple moderation regression analyses revealed that the implicit mindfulness condition had significant beneficial effects for participants with low trait mindfulness. These participants reported higher situational self-esteem as well as less negative affect, perceived stress, and self-reported physiological arousal than their counterparts in the control condition. Cortisol analyses revealed that participants in the implicit mindfulness condition, regardless of level of trait mindfulness, showed a greater decline in cortisol during the early recovery stage compared to those in the control condition. Overall, results suggest that implicitly activating mindfulness can mitigate the psychological and physiological effects of a social stressor. PMID- 27378974 TI - Using the Visual World Paradigm to Study Retrieval Interference in Spoken Language Comprehension. AB - The cue-based retrieval theory (Lewis et al., 2006) predicts that interference from similar distractors should create difficulty for argument integration, however this hypothesis has only been examined in the written modality. The current study uses the Visual World Paradigm (VWP) to assess its feasibility to study retrieval interference arising from distractors present in a visual display during spoken language comprehension. The study aims to extend findings from Van Dyke and McElree (2006), which utilized a dual-task paradigm with written sentences in which they manipulated the relationship between extra-sentential distractors and the semantic retrieval cues from a verb, to the spoken modality. Results indicate that retrieval interference effects do occur in the spoken modality, manifesting immediately upon encountering the verbal retrieval cue for inaccurate trials when the distractors are present in the visual field. We also observed indicators of repair processes in trials containing semantic distractors, which were ultimately answered correctly. We conclude that the VWP is a useful tool for investigating retrieval interference effects, including both the online effects of distractors and their after-effects, when repair is initiated. This work paves the way for further studies of retrieval interference in the spoken modality, which is especially significant for examining the phenomenon in pre-reading children, non-reading adults (e.g., people with aphasia), and spoken language bilinguals. PMID- 27378975 TI - The Influence of the Social Environment Context in Stress and Coping in Sport. AB - Lazarus (1999) model of stress and coping is based on the reciprocal interaction between the person and the environment. The aim of this study therefore was to examine whether the social environment (significant others) are of influence on the stress and coping of team athletes. The study consisted of two separate studies in which a total of 12 team athletes participated. First, six field hockey players (two males, four females) aged 18-29 years (M = 23.0 years) participated in a diary study. Second, six team athletes of different sports (two males, four females) aged 24-29 years (M = 25.8 years) were interviewed. The results showed that in particular teammates are important for the appraisal of stress and coping in team sports. For over half (i.e., 51.5%) of the reported stressors in the diary study the participants felt that others were of influence on their coping. Team athletes experienced the highest stress intensity during competition, or when they appraised the situation as a threat. When others were of influence the team athletes were most likely to appraise the situation as a challenge and use problem- or emotion-focused coping strategies. These finding might provide a new portal for intervention to enhance coping with stress in sport and enhance performance and satisfaction. PMID- 27378976 TI - Editorial: Overlap of Neural Systems for Processing Language and Music. PMID- 27378977 TI - Motivational Hierarchy in the Chinese Brain: Primacy of the Individual Self, Relational Self, or Collective Self? AB - According to the three-tier hierarchy of motivational potency in the self system, the self can be divided into individual self, relational self, and collective self, and individual self is at the top of the motivational hierarchy in Western culture. However, the motivational primacy of the individual self is challenged in Chinese culture, which raises the question about whether the three-tier hierarchy of motivational potency in the self system can be differentiated in the collectivist brain. The present study recorded the event-related potentials (ERPs) to evaluate brain responses when participants gambled for individual self, for a close friend (relational self), or for the class (collective self). The ERP results showed that when outcome feedback was positive, gambling for individual self evoked a larger reward positivity compared with gambling for a friend or for the class, while there is no difference between the latter two conditions. In contrast, when outcome feedback was negative, no significant effect was found between conditions. The present findings provide direct electrophysiological evidence that individual self is at the top of the three-tier hierarchy of the motivational system in the collectivist brain, which supports the classical pancultural view that individual self has motivational primacy. PMID- 27378978 TI - Exploring Selective Exposure and Confirmation Bias as Processes Underlying Employee Work Happiness: An Intervention Study. AB - Employee psychological capital (PsyCap), perceptions of organizational virtue (OV), and work happiness have been shown to be associated within and over time. This study examines selective exposure and confirmation bias as potential processes underlying PsyCap, OV, and work happiness associations. As part of a quasi-experimental study design, school staff (N = 69) completed surveys at three time points. After the first assessment, some staff (n = 51) completed a positive psychology training intervention. Results of descriptive statistics, correlation, and regression analyses on the intervention group provide some support for selective exposure and confirmation bias as explanatory mechanisms. In focusing on the processes through which employee attitudes may influence work happiness this study advances theoretical understanding, specifically of selective exposure and confirmation bias in a field study context. PMID- 27378979 TI - Incarceration and Family Stress as Understood through the Family Process Theory: Evidence from Hong Kong. AB - The myriad of negative effects brought about by the incarceration of a family member have consistently been demonstrated in research. However, previous works have tended to focus on the perspectives of family members separately, rather than exploring the dynamic relationships within the family as an entire unit. Moreover, such research is still limited in the Chinese cultural context. Thus, the current study aimed to examine the applicability of the Family Process Theory on a small sample of Chinese fathers who were imprisoned and have returned to their communities, conceptualizing the challenges faced by their families under the theoretical elements of rules of transformation, rituals, ambiguous loss, and boundary ambiguity. A total of 17 participants were recruited through the assistance of service organizations, and data were collected via semi-structured interviews. As congruent with the theory, inmates' families were found to come across problems particularly in the transitioning phase and establishment of new rituals, while ambiguity surrounding the incarceration and the blurred role of the father led to problems with fatherhood identity both during and after the incarceration. Recommendations are made, in line with these findings and the suggestions of ex-prisoners, for services to have more of a focus on preserving the integrity of inmates' families. Given the right circumstances, families can even serve as a motivator for incarcerated fathers to improve themselves and mature, leveraging the important supportive role of the family and the fear of again being separated from one's family as effective deterrents to recidivism. PMID- 27378980 TI - The Revised Identity Style Inventory: Factor Structure and Validity in Italian Speaking Students. AB - The purpose of this study was to evaluate the factor structure and convergent and discriminant validity of scores on an Italian translation of the Revised Identity Style Inventory (ISI-5) with samples of 237 adolescents (50 males, M age = 18.04, SD = .86) and 268 university students (42 males, M age = 22.71, SD = 3.70). Confirmatory Factor Analysis indicated that a three-factor solution provided a good fit, which was invariant across age and sex groups. The theoretically relationships between scores on the ISI and scores on measures of reasoning and identity processes, identity commitment, and social desirability were partially consistent, thus further studies are needed to give more evidence to the convergent and discriminant validity. PMID- 27378981 TI - Age-Related Changes in Children's Associations of Economic Resources and Race. AB - Age-related changes in children's associations of economic resources and race were investigated. The sample (N = 308) included 5-6 year-olds (n = 153, M = 6.01 years, SD = 0.33 years) and 10-11 year-olds (n = 155, M = 11.12 years, SD = 0.59 years) of African-American (n = 93), European-American (n = 92), Latino (n = 62), Asian-American (n = 23), and multi-racial or multi-ethnic (n = 26) background. Participants matched pairs of target children (African-American and European American) with visual indicators of low, middle, and high economic status. Children's associations of economic resources with racial groups changed with age, and reflected different associations at high, middle, and low levels of the economic spectrum. Specifically, children associated targets of both races with middle economic status at a comparable rate, and with age, increasingly associated targets of both races with indicators of middle economic status. By contrast, both younger and older children associated African-American targets with indicators of low economic status more frequently than European-American targets. Finally, children associated African-American targets with indicators of high economic status less frequently with age, resulting in a perceived disparity in favor of European-American targets at high economic status among older children that was not present among younger children. No differences were found by participants' own racial or ethnic background. These results highlight the need to move beyond a dichotomized view (rich or poor) to include middle economic status when examining children's associations of economic resources and race. PMID- 27378982 TI - Beat Perception and Sociability: Evidence from Williams Syndrome. AB - Beat perception in music has been proposed to be a human universal that may have its origins in adaptive processes involving temporal entrainment such as social communication and interaction. We examined beat perception skills in individuals with Williams syndrome (WS), a genetic, neurodevelopmental disorder. Musical interest and hypersociability are two prominent aspects of the WS phenotype although actual musical and social skills are variable. On a group level, beat and meter perception skills were poorer in WS than in age-matched peers though there was significant individual variability. Cognitive ability, sound processing style, and musical training predicted beat and meter perception performance in WS. Moreover, we found significant relationships between beat and meter perception and adaptive communication and socialization skills in WS. Results have implications for understanding the role of predictive timing in both music and social interactions in the general population, and suggest music as a promising avenue for addressing social communication difficulties in WS. PMID- 27378984 TI - Self-regulation and Beyond: Affect Regulation and the Infant-Caregiver Dyad. AB - In the available psychological literature, affect regulation is fundamentally considered in terms of self-regulation, and according to this standard picture, the contribution of other people in our affect regulation has been viewed in terms of socially assisted self-regulation. The present article challenges this standard picture. By focusing on affect regulation as it unfolds in early infancy, it will be argued that instead of being something original and fundamental, self-regulation developmentally emerges from the basis of a further type of affect regulation. While infants' capacities in recognizing, understanding, and modifying their own affective states are initially immature and undeveloped, affect regulation is initially managed by the other: it is initially the self, and not the other, that plays the role of an assistant in affect regulation. To capture this phenomenon, the concepts of "auto-matic," "hetero-matic," and "altero-matic" affect regulation will be introduced and their interrelations elaborated. By showing how the capacity of affective self regulation, which is characteristic to maturity, is developmentally achieved by internalizing regulative functions that, at the outset of development, are managed by the caregiver, it will be argued that altero-matic affect regulation is an autonomous type of affect regulation and the developmental basis for self regulation. PMID- 27378985 TI - Assessing Workplace Relational Civility (WRC) with a New Multidimensional "Mirror" Measure. AB - This article first introduces a new psychological construct and then presents the psychometric properties of a new multidimensional measure for assessing workplace relational civility (WRC). This new self-report mirror measure has two specular sections (Part A-Me with others; Part B-Others with me) that can assess individuals' relational patterns regarding civility and that can help reduce the bias in the assessment process. The results of exploratory factor analysis revealed a factor structure with three robust dimensions [relational decency (RD), relational culture (RCu), and relational readiness (RR)] exhibiting good values of internal consistency. Confirmatory factor analysis showed, in turn, a good fit of the model to the data. The correlations between the sections of the measure and the 11 instruments used were significant and in the expected directions. These results suggest that this new, brief mirror measure for assessing WRC can be easily employed in different organizational contexts to open different typologies of actions on the basis of the three dimensions, thereby facilitating the construction of a safer and more decent relational work environment. PMID- 27378983 TI - Parental Substance Abuse As an Early Traumatic Event. Preliminary Findings on Neuropsychological and Personality Functioning in Young Drug Addicts Exposed to Drugs Early. AB - Parental substance use is a major risk factor for child development, heightening the risk of drug problems in adolescence and young adulthood, and exposing offspring to several types of traumatic events. First, prenatal drug exposure can be considered a form of trauma itself, with subtle but long-lasting sequelae at the neuro-behavioral level. Second, parents' addiction often entails a childrearing environment characterized by poor parenting skills, disadvantaged contexts and adverse childhood experiences (ACEs), leading to dysfunctional outcomes. Young adults born from/raised by parents with drug problems and diagnosed with a Substance Used Disorder (SUD) themselves might display a particularly severe condition in terms of cognitive deficits and impaired personality function. This preliminary study aims to investigate the role of early exposure to drugs as a traumatic event, capable of affecting the psychological status of young drug addicts. In particular, it intends to examine the neuropsychological functioning and personality profile of young adults with severe SUDs who were exposed to drugs early in their family context. The research involved three groups, each consisting of 15 young adults (aged 18-24): a group of inpatients diagnosed with SUDs and exposed to drugs early, a comparison group of non-exposed inpatients and a group of non-exposed youth without SUDs. A neuropsychological battery (Esame Neuropsicologico Breve-2), an assessment procedure for personality disorders (Shedler-Westen Assessment Procedure-200) and the Symptom CheckList-90-Revised were administered. According to present preliminary results, young drug addicts exposed to drugs during their developmental age were characterized by elevated rates of neuropsychological impairments, especially at the expense of attentive and executive functions (EF); personality disorders were also common but did not differentiate them from non exposed youth with SUDs. Alternative multi-focused prevention and intervention programs are needed for children of drug-misusing parents, addressing EF and adopting a trauma-focused approach. PMID- 27378986 TI - What's in a Day? A Guide to Decomposing the Variance in Intensive Longitudinal Data. AB - In recent years there has been a growing interest in the use of intensive longitudinal research designs to study within-person processes. Examples are studies that use experience sampling data and autoregressive modeling to investigate emotion dynamics and between-person differences therein. Such designs often involve multiple measurements per day and multiple days per person, and it is not clear how this nesting of the data should be accounted for: That is, should such data be considered as two-level data (which is common practice at this point), with occasions nested in persons, or as three-level data with beeps nested in days which are nested in persons. We show that a significance test of the day-level variance in an empty three-level model is not reliable when there is autocorrelation. Furthermore, we show that misspecifying the number of levels can lead to spurious or misleading findings, such as inflated variance or autoregression estimates. Throughout the paper we present instructions and R code for the implementation of the proposed models, which includes a novel three-level AR(1) model that estimates moment-to-moment inertia and day-to-day inertia. Based on our simulations we recommend model selection using autoregressive multilevel models in combination with the AIC. We illustrate this method using empirical emotion data from two independent samples, and discuss the implications and the relevance of the existence of a day level for the field. PMID- 27378987 TI - Neural Correlates of Math Gains Vary Depending on Parental Socioeconomic Status (SES). AB - We used functional magnetic resonance imaging (fMRI) to examine the neural predictors of math development, and asked whether these predictors vary as a function of parental socioeconomic status (SES) in children ranging in age from 8 to 13 years. We independently localized brain regions subserving verbal versus spatial processing in order to characterize relations between activation in these regions during an arithmetic task and long-term change in math skill (up to 3 years). Neural predictors of math gains encompassed brain regions subserving both verbal and spatial processing, but the relation between relative reliance on these regions and math skill growth varied depending on parental SES. Activity in an area of the left inferior frontal gyrus (IFG) identified by the verbal localizer was related to greater growth in math skill at the higher end of the SES continuum, but lesser improvements at the lower end. Activity in an area of the right superior parietal cortex identified by the spatial localizer was related to greater growth in math skill at the lower end of the SES continuum, but lesser improvements at the higher end. Results highlight early neural mechanisms as possible neuromarkers of long-term arithmetic learning and suggest that neural predictors of math gains vary with parental SES. PMID- 27378988 TI - Comparison of Athletes' Proneness to Depressive Symptoms in Individual and Team Sports: Research on Psychological Mediators in Junior Elite Athletes. AB - Depression among elite athletes is a topic of increasing interest and public awareness. Currently, empirical data on elite athletes' depressive symptoms are rare. Recent results indicate sport-related mechanisms and effects on depression prevalence in elite athlete samples; specific factors associated with depression include overtraining, injury, and failure in competition. One such effect is that athletes competing in individual sports were found to be more prone to depressive symptoms than athletes competing in team sports. The present study examined this effect by testing three possible, psychological mediators based on theoretical and empirical assumptions: namely, cohesion in team or training groups; perception of perfectionistic expectations from others; and negative attribution after failure. In a cross-sectional study, 199 German junior elite athletes (M age = 14.96; SD = 1.56) participated and completed questionnaires on perfectionism, cohesion, attribution after failure, and depressive symptoms. Mediation analysis using path analysis with bootstrapping was used for data analysis. As expected, athletes in individual sports showed higher scores in depression than athletes in team sports [t(197) = 2.05; p < 0.05; d = 0.30]. Furthermore, negative attribution after failure was associated with individual sports (beta = 0.27; p < 0.001), as well as with the dependent variable depression (beta = 0.26; p < 0.01). Mediation hypothesis was supported by a significant indirect effect (beta = 0.07; p < 0.05). Negative attribution after failure mediated the relationship between individual sports and depression scores. Neither cohesion nor perfectionism met essential criteria to serve as mediators: cohesion was not elevated in either team or individual sports, and perfectionism was positively related to team sports. The results support the assumption of previous findings on sport-specific mechanisms (here the effect between individual and team sports) contributing to depressive symptoms among elite athletes. Additionally, attribution after failure seems to play an important role in this regard and could be considered in further research and practitioners in the field of sport psychology. PMID- 27378989 TI - Does the Component Processes Task Assess Text-Based Inferences Important for Reading Comprehension? A Path Analysis in Primary School Children. AB - Using a component processes task (CPT) that differentiates between higher-level cognitive processes of reading comprehension provides important advantages over commonly used general reading comprehension assessments. The present study contributes to further development of the CPT by evaluating the relative contributions of its components (text memory, text inferencing, and knowledge integration) and working memory to general reading comprehension within a single study using path analyses. Participants were 173 third- and fourth-grade children. As hypothesized, knowledge integration was the only component of the CPT that directly contributed to reading comprehension, indicating that the text inferencing component did not assess inferential processes related to reading comprehension. Working memory was a significant predictor of reading comprehension over and above the component processes. Future research should focus on finding ways to ensure that the text-inferencing component taps into processes important for reading comprehension. PMID- 27378990 TI - Editorial: The Social Nature of Emotions. PMID- 27378991 TI - A Simulation Study of Threats to Validity in Quasi-Experimental Designs: Interrelationship between Design, Measurement, and Analysis. AB - The Campbellian tradition provides a conceptual framework to assess threats to validity. On the other hand, different models of causal analysis have been developed to control estimation biases in different research designs. However, the link between design features, measurement issues, and concrete impact estimation analyses is weak. In order to provide an empirical solution to this problem, we use Structural Equation Modeling (SEM) as a first approximation to operationalize the analytical implications of threats to validity in quasi experimental designs. Based on the analogies established between the Classical Test Theory (CTT) and causal analysis, we describe an empirical study based on SEM in which range restriction and statistical power have been simulated in two different models: (1) A multistate model in the control condition (pre-test); and (2) A single-trait-multistate model in the control condition (post-test), adding a new mediator latent exogenous (independent) variable that represents a threat to validity. Results show, empirically, how the differences between both the models could be partially or totally attributed to these threats. Therefore, SEM provides a useful tool to analyze the influence of potential threats to validity. PMID- 27378992 TI - Exercise Experiences and Changes in Affective Attitude: Direct and Indirect Effects of In Situ Measurements of Experiences. AB - OBJECTIVES: The purpose of this study was to examine the relationship between exercise experiences (perceptions of competence, perceived exertion, acute affective responses to exercise) and affective attitudes toward exercise. This relationship was analyzed in a non-laboratory setting during a 13-weeks exercise program. MATERIALS AND METHODS: 56 women and 49 men (aged 35-65 years; M age = 50.0 years; SD = 8.2 years) took part in the longitudinal study. Affective responses to exercise (affective valence, positive activation, calmness) as well as perceptions of competence and perceived exertion were measured at the beginning, during, and end of three exercise sessions within the 13-weeks exercise program. Affective attitude toward exercise were measured before and at the end of the exercise program. A two-level path analysis was conducted. The direct and indirect effects of exercise experiences on changes in affective attitude were analyzed on the between-person level: firstly, it was tested whether perceptions of competence and perceived exertion directly relate to changes in affective attitude. Secondly, it was assessed whether perceptions of competence and perceived exertion indirectly relate to changes in affective attitudes-imparted via the affective response during exercise. RESULTS AND CONCLUSION: At the between-person level, a direct effect on changes in affective attitude was found for perceptions of competence (beta = 0.24, p < 0.05). The model revealed one significant indirect pathway between perceived exertion and changes in affective attitude via positive activation: on average, the less strenuous people perceive physical exercise to be, the more awake they will feel during exercise (beta = -0.57, p < 0.05). Those people with higher average levels of positive activation during exercise exhibit more improvements in affective attitudes toward exercise from the beginning to the end of the 13-weeks exercise program (beta = 0.24, p < 0.05). Main study results have revealed that in situ experiences predicted changes in affective attitude during multi-week exercise programs. These relevant in situ experiences encompass cognitive factors, the sensation of interoceptive cues, and affective responses to exercise. Considering the predictive role of affective attitudes for exercise behavior, these findings suggest that exercise interventions should put greater emphasis on specific exercise experiences. PMID- 27378993 TI - Blind-Sight vs. Degraded-Sight: Different Measures Tell a Different Story. AB - Blindsight patients can detect, localize, and discriminate visual stimuli in their blind field, despite denying being able to see the stimuli. However, the literature documents the cases of blindsight patients who demonstrated a preserved degree of awareness in their impaired visual field. The aim of this study is to investigate the nature of visual processing within the impaired visual field and to ask whether it reflects pure unconscious behavior or conscious, yet degraded, vision. A hemianopic patient (SL) with a complete lesion to the left primary visual cortex was tested. SL was asked to discriminate several stimulus features (orientation, color, contrast, and motion) presented in her impaired visual field in a two-alternative forced-choice task. SL had to report her subjective experience: in the first experiment as "seen" or "guessed," whereas in the second experiment as the degree of clarity of her experience according to the perceptual awareness scale. In the first experiment, SL demonstrated a performance above-chance in the discrimination task for "guessed" trials, thus showing type 1 blindsight. In the second experiment, however, SL showed above-chance performance only when she reported a certain degree of awareness, thus showing that SL's preserved discrimination ability relies on conscious vision. These data show that graded measures to assess awareness, which can better tap on the complexity of conscious experience, need to be used in order to differentiate genuine forms of blindsight from degraded conscious vision. PMID- 27378995 TI - Editorial: Historical Roots of Psychopathology. PMID- 27378994 TI - The Relationship between Expertise in Sports, Visuospatial, and Basic Cognitive Skills. AB - Team sports place high demands on visuospatial and other cognitive skills. However, there is a lack of research on visuospatial skills of elite athletes and there are heterogeneous results on basic cognitive skills of this population. Therefore, this series of studies tested different cognitive skills in elite team sports athletes. In Experiment 1, elite athletes were compared to recreational athletes, but no differences were observed between the groups in choice response time (CRT) and mental rotation (MR). To see if differences could be observed when the tested groups had a greater difference in expertise and more representative stimuli, in Experiment 2, we tested CRT and MR of elite athletes who had higher level of expertise, and we also used three-dimensional human stimuli. Overall, we still found no differences in MR; however, elite athletes did have shorter CRTs. In Experiment 3, instead of testing MR, we compared elite athletes' and recreational athletes' basic cognitive skills, such as processing speed, letter readout speed, memory span, and sustained attention. We found that elite athletes only performed better in sustained attention. Building on this data, in a supplementary analysis (Experiment 4) we tested whether MR and CRTs are correlated with basic cognitive skills. Results show that processing speed is the best predictor for MR, whereas letter readout speed explains most of the variance in CRTs. Finally, we discuss these findings against the backdrop of expertise and offer implications for future studies on mental rotation. PMID- 27378997 TI - Effects of Semantic Context and Fundamental Frequency Contours on Mandarin Speech Recognition by Second Language Learners. AB - Speech recognition by second language (L2) learners in optimal and suboptimal conditions has been examined extensively with English as the target language in most previous studies. This study extended existing experimental protocols (Wang et al., 2013) to investigate Mandarin speech recognition by Japanese learners of Mandarin at two different levels (elementary vs. intermediate) of proficiency. The overall results showed that in addition to L2 proficiency, semantic context, F0 contours, and listening condition all affected the recognition performance on the Mandarin sentences. However, the effects of semantic context and F0 contours on L2 speech recognition diverged to some extent. Specifically, there was significant modulation effect of listening condition on semantic context, indicating that L2 learners made use of semantic context less efficiently in the interfering background than in quiet. In contrast, no significant modulation effect of listening condition on F0 contours was found. Furthermore, there was significant interaction between semantic context and F0 contours, indicating that semantic context becomes more important for L2 speech recognition when F0 information is degraded. None of these effects were found to be modulated by L2 proficiency. The discrepancy in the effects of semantic context and F0 contours on L2 speech recognition in the interfering background might be related to differences in processing capacities required by the two types of information in adverse listening conditions. PMID- 27378996 TI - Action Video Game Training for Healthy Adults: A Meta-Analytic Study. AB - Action video game (AVG) has attracted increasing attention from both the public and from researchers. More and more studies found video game training improved a variety of cognitive functions. However, it remains controversial whether healthy adults can benefit from AVG training, and whether young and older adults benefit similarly from AVG training. In the present study, we aimed to quantitatively assess the AVG training effect on the cognitive ability of adults and to compare the training effects on young and older adults by conducting a meta-analysis on previous findings. We systematically searched video game training studies published between January 1986 and July 2015. Twenty studies were included in the present meta-analysis, for a total of 313 participants included in the training group and 323 participants in the control group. The results demonstrate that healthy adults achieve moderate benefit from AVG training in overall cognitive ability and moderate to small benefit in specific cognitive domains. In contrast, young adults gain more benefits from AVG training than older adults in both overall cognition and specific cognitive domains. Age, education, and some methodological factors, such as the session duration, session number, total training duration, and control group type, modulated the training effects. These meta-analytic findings provide evidence that AVG training may serve as an efficient way to improve the cognitive performance of healthy adults. We also discussed several directions for future AVG training studies. PMID- 27378998 TI - Attending to Race (or Gender) Does Not Increase Race (or Gender) Aftereffects. AB - Recent research has shown that attention can influence the strength of face aftereffects. For example, attending to changes in facial features increases the strength of identity and figural aftereffects relative to passive viewing (Rhodes et al., 2011). Here, we ask whether attending to a specific social dimension of a face (such as race or gender) influences the strength of face aftereffects along that dimension. Across three experiments, participants completed many single-shot face adaptation trials. In each trial, participants observed a computer-generated adapting face for 5 s while instructed to focus on either the race or gender of that adapting face. Adapting faces were either Asian and female or Caucasian and male. In Experiment 1, all trials included an intermediate question (IQ) following each adaptation period, soliciting a rating of the adapting face on the attended dimension (e.g., race). In Experiment 2, only half of the trials included this IQ, and in Experiment 3 only a quarter of the trials did. In all three experiments, participants were subsequently presented with a race- and gender-neutral face and asked to rate it on either the attended dimension (e.g., race, attention-congruent trials) or the unattended dimension (e.g., gender, attention-incongruent trials) using a seven-point scale. Overall, participants showed significant aftereffects in all conditions, manifesting as (i) higher Asian ratings of the neutral faces following Caucasian vs. Asian adapting faces and (ii) higher female ratings of neutral faces following male vs. female adapting faces. Intriguingly, although reaction times were shorter during attention-congruent vs. attention-incongruent trials, aftereffects were not stronger along attention-congruent than attention-incongruent dimensions. Our results suggest that attending to a facial dimension such as race or gender does not result in increased adaptation to that dimension. PMID- 27379000 TI - Is Accessing of Words Affected by Affective Valence Only? A Discrete Emotion View on the Emotional Congruency Effect. AB - This paper advances the discussion on which emotion information affects word accessing. Emotion information, which is formed as a result of repeated experiences, is primary and necessary in learning and representing word meanings. Previous findings suggested that valence (i.e., positive or negative) denoted by words can be automatically activated and plays a role in many significant cognitive processes. However, there has been a lack of discussion about whether discrete emotion information (i.e., happiness, anger, sadness, and fear) is also involved in these processes. According to the hierarchy model, emotions are considered organized within an abstract-to-concrete hierarchy, in which emotion prototypes are organized following affective valence. By controlling different congruencies of emotion relations (i.e., matches or mismatches between valences and prototypes of emotion), the present study showed both an evaluative congruency effect (Experiment 1) and a discrete emotional congruency effect (Experiment 2). These findings indicate that not only affective valences but also discrete emotions can be activated under the present priming lexical decision task. However, the present findings also suggest that discrete emotions might be activated at the later priming stage as compared to valences. The present work provides evidence that information about discrete emotion could be involved in word processing. This might be a result of subjects' embodied experiences. PMID- 27378999 TI - Compulsive Buying Behavior: Clinical Comparison with Other Behavioral Addictions. AB - Compulsive buying behavior (CBB) has been recognized as a prevalent mental health disorder, yet its categorization into classification systems remains unsettled. The objective of this study was to assess the sociodemographic and clinic variables related to the CBB phenotype compared to other behavioral addictions. Three thousand three hundred and twenty four treatment-seeking patients were classified in five groups: CBB, sexual addiction, Internet gaming disorder, Internet addiction, and gambling disorder. CBB was characterized by a higher proportion of women, higher levels of psychopathology, and higher levels in the personality traits of novelty seeking, harm avoidance, reward dependence, persistence, and cooperativeness compared to other behavioral addictions. Results outline the heterogeneity in the clinical profiles of patients diagnosed with different behavioral addiction subtypes and shed new light on the primary mechanisms of CBB. PMID- 27379001 TI - Affective Priming by Simple Geometric Shapes: Evidence from Event-related Brain Potentials. AB - Previous work has demonstrated that simple geometric shapes may convey emotional meaning using various experimental paradigms. However, whether affective meaning of simple geometric shapes can be automatically activated and influence the evaluations of subsequent stimulus is still unclear. Thus the present study employed an affective priming paradigm to investigate whether and how two geometric shapes (circle vs. downward triangle) impact on the affective processing of subsequently presented faces (Experiment 1) and words (Experiment 2). At behavioral level, no significant effect of affective congruency was found. However, ERP results in Experiment 1 and 2 showed a typical effect of affective congruency. The LPP elicited by affectively incongruent trials was larger compared to congruent trials. Our results provide support for the notion that downward triangle is perceived as negative and circle as positive and their emotional meaning can be activated automatically and then exert an influence on the electrophysiological processing of subsequent stimuli. The lack of significant congruent effect in behavioral measures and the inversed N400 congruent effect might reveal that the affective meaning of geometric shapes is weak because they are just abstract threatening cues rather than real threat. In addition, because no male participants are included in the present study, our findings are limited to females. PMID- 27379002 TI - Semantic Verbal Fluency in Children with and without Autism Spectrum Disorder: Relationship with Chronological Age and IQ. AB - We administered a semantic verbal fluency (SVF) task to two groups of children (age range from 5 to 8): 47 diagnosed with Autism Spectrum Disorder (ASD Group) and 53 with typical development (Comparison Group), matched on gender, chronological age, and non-verbal IQ. Four specific indexes were calculated from the SVF task, reflecting the different underlying cognitive strategies used: clustering (component of generativity and lexical-semantic access), and switching (executive component, cognitive flexibility). First, we compared the performance of the two groups on the different SVF task indicators, with the ASD group scoring lower than the Comparison Group, although the difference was greater on switching than on clustering. Second, we analyzed the relationships between the different SVF measures and chronological age, verbal IQ and non-verbal IQ. While in the Comparison Group chronological age was the main predictor of performance on the SVF task, in the ASD Group verbal IQ was the best predictor. In the children with ASD, therefore, greater linguistic competence would be associated with better performance on the SVF task, which should be taken into account in speech therapies designed to achieve improvements in linguistic generativity and cognitive flexibility. PMID- 27379003 TI - Character Decomposition and Transposition Processes in Chinese Compound Words Modulates Attentional Blink. AB - The attentional blink (AB) is the phenomenon in which the identification of the second of two targets (T2) is attenuated if it is presented less than 500 ms after the first target (T1). Although the AB is eliminated in canonical word conditions, it remains unclear whether the character order in compound words affects the magnitude of the AB. Morpheme decomposition and transposition of Chinese two-character compound words can provide an effective means to examine AB priming and to assess combinations of the component representations inherent to visual word identification. In the present study, we examined the processing of consecutive targets in a rapid serial visual presentation (RSVP) paradigm using Chinese two-character compound words in which the two characters were transposed to form meaningful words or meaningless combinations (reversible, transposed, or canonical words). We found that when two Chinese characters that form a compound word, regardless of their order, are presented in an RSVP sequence, the likelihood of an AB for the second character is greatly reduced or eliminated compared to when the two characters constitute separate words rather than a compound word. Moreover, the order of the report for the two characters is more likely to be reversed when the normal order of the two characters in a compound word is reversed, especially when the interval between the presentation of the two characters is extremely short. These findings are more consistent with the cognitive strategy hypothesis than the resource-limited hypothesis during character decomposition and transposition of Chinese two-character compound words. These results suggest that compound characters are perceived as a unit, rather than two separate words. The data further suggest that readers could easily understand the text with character transpositions in compound words during Chinese reading. PMID- 27379004 TI - Less Is More: Psychologists Can Learn More by Studying Fewer People. PMID- 27379005 TI - Hyperacute versus Subacute Coiling of Aneurysmal Subarachnoid Hemorrhage a Short term Outcome and Single-Center Experience, Pilot Study. AB - BACKGROUND: After the initial subarachnoid hemorrhage (SAH), rebleeding is the major cause of morbidity and poor outcome, which is maximal in the first 24 h. We supposed that the coiling of ruptured intracranial aneurysms within 24 h of SAH is related to the improved clinical outcome compared with coiling 24 h after aneurysmal SAH. OBJECTIVE: We examined whether coiling ruptured aneurysms within 24 h of aneurysmal SAH is associated with better early 24 h and late 30 days outcome. METHOD: This prospective study was carried on 30 patients with aneurysmal SAH presenting to the Alexandria University Hospital and Insurance Main Hospital during the period from February 2013 to May 2014. They were divided into two groups: Group I (10 patients treated within 24 h of presentation) and Group II (20 patients treated after 24 h of presentation). Time interval from presentation to treatment were 78.60 and 10.60 h for subacute and hyperacute group, respectively. All patients were treated with endovascular coiling. Change between admission and immediate postoperative World Federation of Neurosurgeons classification Scale was measured for early outcome, while remote outcome was measured by modified Rankin Scale at 30 days follow-up. RESULTS: There was a clinical improvement regarding early 24 h outcome (weighted by postoperative WFNS grade) and on late 30 days outcome (weighted by Modified Rankin Scale Score) in the group managed within 24 h versus who were treated after 24 h (P = 0.049 and P = 0.024, respectively). There was a significant decrease in the incidence of clinical rebleeding detected by postoperative computed tomography (CT) of the brain in patients undergoing aneurysm treatment within 24 h (P = 0.029). CONCLUSION: The study affirms evidence that the management of ruptured intracranial aneurysms within 24 h of SAH is associated with better immediate and short-term clinical outcome. PMID- 27379007 TI - Slow Bursting Neurons of Mouse Cortical Layer 6b Are Depolarized by Hypocretin/Orexin and Major Transmitters of Arousal. AB - Neurons firing spontaneously in bursts in the absence of synaptic transmission have been previously recorded in different layers of cortical brain slices. It has been suggested that such neurons could contribute to the generation of alternating UP and DOWN states, a pattern of activity seen during slow-wave sleep. Here, we show that in layer 6b (L6b), known from our previous studies to contain neurons highly responsive to the wake-promoting transmitter hypocretin/orexin (hcrt/orx), there is a set of neurons, endowed with distinct intrinsic properties, which displayed a strong propensity to fire spontaneously in rhythmic bursts. In response to small depolarizing steps, they responded with a delayed firing of action potentials which, upon higher depolarizing steps, invariably inactivated and were followed by a depolarized plateau potential and a depolarizing afterpotential. These cells also displayed a strong hyperpolarization-activated rectification compatible with the presence of an I h current. Most L6b neurons with such properties were able to fire spontaneously in bursts. Their bursting activity was of intrinsic origin as it persisted not only in presence of blockers of ionotropic glutamatergic and GABAergic receptors but also in a condition of complete synaptic blockade. However, a small number of these neurons displayed a mix of intrinsic bursting and synaptically driven recurrent UP and DOWN states. Most of the bursting L6b neurons were depolarized and excited by hcrt/orx through a direct postsynaptic mechanism that led to tonic firing and eventually inactivation. Similarly, they were directly excited by noradrenaline, histamine, dopamine, and neurotensin. Finally, the intracellular injection of these cells with dye and their subsequent Neurolucida reconstruction indicated that they were spiny non-pyramidal neurons. These results lead us to suggest that the propensity for slow rhythmic bursting of this set of L6b neurons could be directly impeded by hcrt/orx and other wake-promoting transmitters. PMID- 27379006 TI - A Pathway Proteomic Profile of Ischemic Stroke Survivors Reveals Innate Immune Dysfunction in Association with Mild Symptoms of Depression - A Pilot Study. AB - Depression after stroke is a common occurrence, raising questions as to whether depression could be a long-term biological and immunological sequela of stroke. Early explanations for post-stroke depression (PSD) focused on the neuropsychological/psychosocial effects of stroke on mobility and quality of life. However, recent investigations have revealed imbalances of inflammatory cytokine levels in association with PSD, though to date, there is only one published proteomic pathway analysis testing this hypothesis. Thus, we examined the serum proteome of stroke patients (n = 44, mean age = 63.62 years) and correlated these with the Montgomery-Asberg Depression Rating Scale (MADRS) scores at 3 months post-stroke. Overall, the patients presented with mild depression symptoms on the MADRS, M = 6.40 (SD = 7.42). A discovery approach utilizing label-free relative quantification was employed utilizing an LC-ESI MS/MS coupled to a LTQ-Orbitrap Elite (Thermo-Scientific). Identified peptides were analyzed using the gene set enrichment approach on several different genomic databases that all indicated significant downregulation of the complement and coagulation systems with increasing MADRS scores. Complement and coagulation systems are traditionally thought to play a key role in the innate immune system and are established precursors to the adaptive immune system through pro inflammatory cytokine signaling. Both systems are known to be globally affected after ischemic or hemorrhagic stroke. Thus, our results suggest that lowered complement expression in the periphery in conjunction with depressive symptoms post-stroke may be a biomarker for incomplete recovery of brain metabolic needs, homeostasis, and inflammation following ischemic stroke damage. Further proteomic investigations are now required to construct the temporal profile, leading from acute lesion damage to manifestation of depressive symptoms. Overall, the findings provide support for the involvement of inflammatory and immune mechanisms in PSD symptoms and further demonstrate the value and feasibility of the proteomic approach in stroke research. PMID- 27379010 TI - Editorial: When Physics Meets Biology; Biomechanics and Biology of Traumatic Brain Injury. PMID- 27379009 TI - Degradation of Binocular Coordination during Sleep Deprivation. AB - To aid a clear and unified visual perception while tracking a moving target, both eyes must be coordinated, so the image of the target falls on approximately corresponding areas of the fovea of each eye. The movements of the two eyes are decoupled during sleep, suggesting a role of arousal in regulating binocular coordination. While the absence of visual input during sleep may also contribute to binocular decoupling, sleepiness is a state of reduced arousal that still allows for visual input, providing a context within which the role of arousal in binocular coordination can be studied. We examined the effects of sleep deprivation on binocular coordination using a test paradigm that we previously showed to be sensitive to sleep deprivation. We quantified binocular coordination with the SD of the distance between left and right gaze positions on the screen. We also quantified the stability of conjugate gaze on the target, i.e., gaze target synchronization, with the SD of the distance between the binocular average gaze and the target. Sleep deprivation degraded the stability of both binocular coordination and gaze-target synchronization, but between these two forms of gaze control the horizontal and vertical components were affected differently, suggesting that disconjugate and conjugate eye movements are under different regulation of attentional arousal. The prominent association found between sleep deprivation and degradation of binocular coordination in the horizontal direction may be used for a fit-for-duty assessment. PMID- 27379008 TI - Major Histocompatibility Complex I Expression by Motor Neurons and Its Implication in Amyotrophic Lateral Sclerosis. AB - Neuronal expression of major histocompatibility complex I (MHCI)-related molecules in adults and during CNS diseases is involved in the synaptic plasticity and axonal regeneration with mechanisms either dependent or independent of their immune functions. Motor neurons are highly responsive in triggering the expression of MHCI molecules during normal aging or following insults and diseases, and this has implications in the synaptic controls, axonal regeneration, and neuromuscular junction stability of these neurons. We recently reported that MHCI and immunoproteasome are strongly activated in spinal motor neurons and their peripheral motor axon in a mouse model of familial amyotrophic lateral sclerosis (ALS) during the course of the disease. This response was prominent in ALS mice with slower disease progression in which the axonal structure and function was better preserved than in fast-progressing mice. This review summarizes and discusses our observations in the light of knowledge about the possible role of MHCI in motor neurons providing additional insight into the pathophysiology of ALS. PMID- 27379011 TI - Visual Rehabilitation in Chronic Cerebral Blindness: A Randomized Controlled Crossover Study. AB - The treatment of patients suffering from cerebral blindness following stroke is a topic of much recent interest. Several types of treatment are under investigation, such as substitution with prisms and compensation training of saccades. A third approach, aimed at vision restitution is controversial, as a proper controlled study design is missing. In the current study, 27 chronic stroke patients with homonymous visual field defects were trained at home with a visual training device. We used a discrimination task for two types of stimuli: a static point stimulus and a new optic flow-discontinuity stimulus. Using a randomized controlled crossover design, each patient received two successive training rounds, one with high contrast stimuli in their affected hemifield (test) and one round with low-contrast stimuli in their intact hemifield (control). Goldmann and Humphrey perimetry were performed at the start of the study and following each training round. In addition, reading performance was measured. Goldmann perimetry revealed a statistically significant reduction of the visual field defect after the test training, but not after the control training or after no intervention. For both training rounds combined, Humphrey perimetry revealed that the effect of a directed training (sensitivity change in trained hemifield) exceeded that of an undirected training (sensitivity change in untrained hemifield). The interaction between trained and tested hemifield was just above the threshold of significance (p = 0.058). Interestingly, reduction of the field defect assessed by Goldmann perimetry increases with the difference between defect size as measured by Humphrey and Goldmann perimetry prior to training. Moreover, improvement of visual sensitivity measured by Humphrey perimetry increases with the fraction of non-responsive elements (i.e., more relative field loss) in Humphrey perimetry prior to training. Reading speed revealed a significant improvement after training. Our findings demonstrate that our training can result in reduction of the visual field. Improved reading performance after defect training further supports the significance of our training for improvement in daily life activities. PMID- 27379012 TI - Editorial: The Physiology and Pharmacology of Leucine-rich Repeat GPCRs. PMID- 27379013 TI - Simulated Interventions to Ameliorate Age-Related Bone Loss Indicate the Importance of Timing. AB - Bone remodeling is the continuous process of bone resorption by osteoclasts and bone formation by osteoblasts, in order to maintain homeostasis. The activity of osteoclasts and osteoblasts is regulated by a network of signaling pathways, including Wnt, parathyroid hormone (PTH), RANK ligand/osteoprotegrin, and TGF beta, in response to stimuli, such as mechanical loading. During aging there is a gradual loss of bone mass due to dysregulation of signaling pathways. This may be due to a decline in physical activity with age and/or changes in hormones and other signaling molecules. In particular, hormones, such as PTH, have a circadian rhythm, which may be disrupted in aging. Due to the complexity of the molecular and cellular networks involved in bone remodeling, several mathematical models have been proposed to aid understanding of the processes involved. However, to date, there are no models, which explicitly consider the effects of mechanical loading, the circadian rhythm of PTH, and the dynamics of signaling molecules on bone remodeling. Therefore, we have constructed a network model of the system using a modular approach, which will allow further modifications as required in future research. The model was used to simulate the effects of mechanical loading and also the effects of different interventions, such as continuous or intermittent administration of PTH. Our model predicts that the absence of regular mechanical loading and/or an impaired PTH circadian rhythm leads to a gradual decrease in bone mass over time, which can be restored by simulated interventions and that the effectiveness of some interventions may depend on their timing. PMID- 27379014 TI - Sex and Immunogen-Specific Benefits of Immunotherapy Targeting Islet Amyloid Polypeptide in Transgenic and Wild-Type Mice. AB - Type 2 diabetes mellitus is characterized by the deposition of islet amyloid polypeptide (IAPP) as amyloid in islets, a process thought to be toxic to beta cells. To determine the feasibility of targeting these aggregates therapeutically, we vaccinated transgenic (Tg) mice that overexpress human IAPP and were fed a high-fat diet to promote their diabetic phenotype. Our findings indicate that prophylactic vaccination with IAPP and its derivative IAPP7-19-TT, protects wild-type female mice, but not males, from obesity-induced early mortality, and the derivative showed a strong trend for prolonging the lifespan of Tg females but not males. Furthermore, IAPP7-19-TT-immunized Tg females cleared a glucose bolus more efficiently than controls, while IAPP-immunized Tg females showed an impaired ability to clear a glucose bolus compared to their adjuvant injected Tg controls. Interestingly, IAPP or IAPP7-19-TT treatments had no effect on glucose clearance in Tg males. Overall, these beneficial effects of IAPP targeted immunization depend on Tg status, sex, and immunogen. Hence, future studies in this field should carefully consider these variables that clearly affect the therapeutic outcome. In conclusion, IAPP targeting immunotherapy may have benefits in patients with type 2 diabetes. PMID- 27379015 TI - Role of EPAC in cAMP-Mediated Actions in Adrenocortical Cells. AB - Adrenocorticotropic hormone regulates adrenal steroidogenesis mainly via the intracellular signaling molecule cAMP. The effects of cAMP are principally relayed by activating protein kinase A (PKA) and the more recently discovered exchange proteins directly activated by cAMP 1 and 2 (EPAC1 and EPAC2). While the intracellular roles of PKA have been extensively studied in steroidogenic tissues, those of EPACs are only emerging. EPAC1 and EPAC2 are encoded by the genes RAPGEF3 and RAPGEF4, respectively. Whereas EPAC1 is ubiquitously expressed, the expression of EPAC2 is more restricted, and typically found in endocrine tissues. Alternative promoter usage of RAPGEF4 gives rise to three different isoforms of EPAC2 that vary in their N-termini (EPAC2A, EPAC2B, and EPAC2C) and that exhibit distinct expression patterns. EPAC2A is expressed in the brain and pancreas, EPAC2B in steroidogenic cells of the adrenal gland and testis, and EPAC2C has until now only been found in the liver. In this review, we discuss current knowledge on EPAC expression and function with focus on the known roles of EPAC in adrenal gland physiology. PMID- 27379016 TI - A Review of the Phenomenon of Hysteresis in the Hypothalamus-Pituitary-Thyroid Axis. AB - The existence of a phase of prolonged suppression of TSH despite normalization of serum thyroid hormones over a variable period of time during the recovery of thyrotoxicosis has been documented in literature. Conversely, a temporary elevation of TSH despite attainment of euthyroid levels of serum thyroid hormones following extreme hypothyroidism has also been observed. This rate-independent lag time in TSH recovery is an evidence of a "persistent memory" of the history of dysthyroid states the hypothalamus-pituitary-thyroid (HPT) axis has encountered after the thyroid hormone perturbations have faded out, a phenomenon termed "hysteresis." Notwithstanding its perplexing nature, hysteresis impacts upon the interpretation of thyroid function tests with sufficient regularity that clinicians risk misdiagnosing and implementing erroneous treatment out of ignorance of this aspect of thyrotropic biology. Mathematical modeling of this phenomenon is complicated but may allow the euthyroid set point to be predicted from thyroid function data exhibiting strong hysteresis effects. Such model predictions are potentially useful for clinical management. Although the molecular mechanisms mediating hysteresis remain elusive, epigenetics, such as histone modifications, are probably involved. However, attempts to reverse the process to hasten the resolution of the hysteretic process may not necessarily translate into improved physiology or optimal health benefits. This is not unexpected from teleological considerations, since hysteresis probably represents an adaptive endocrinological response with survival advantages evolutionarily conserved among vertebrates with a HPT system. PMID- 27379017 TI - Exercise and Adipose Tissue Macrophages: New Frontiers in Obesity Research? AB - Obesity is a major public health problem in the twenty-first century. Mutations in genes that regulate substrate metabolism, subsequent dysfunction in their protein products, and other factors, such as increased adipose tissue inflammation, are some underlying etiologies of this disease. Increased inflammation in the adipose tissue microenvironment is partly mediated by the presence of cells from the innate and adaptive immune system. A subset of the innate immune population in adipose tissue include macrophages, termed adipose tissue macrophages (ATMs), which are central players in adipose tissue inflammation. Being extremely plastic, their responses to diverse molecular signals in the microenvironment dictate their identity and functional properties, where they become either pro-inflammatory (M1) or anti-inflammatory (M2). Endurance exercise training exerts global anti-inflammatory responses in multiple organs, including skeletal muscle, liver, and adipose tissue. The purpose of this review is to discuss the different mechanisms that drive ATM-mediated inflammation in obesity and present current evidence of how exercise training, specifically endurance exercise training, modulates the polarization of ATMs from an M1 to an M2 anti-inflammatory phenotype. PMID- 27379018 TI - The Mineralocorticoid Agonist Fludrocortisone Promotes Survival and Proliferation of Adult Hippocampal Progenitors. AB - Glucocorticoid receptor (GR) activation has been shown to reduce adult hippocampal progenitor cell proliferation and neurogenesis. By contrast, mineralocorticoid receptor (MR) signaling is associated with neuronal survival in the dentate gyrus of the hippocampus, and impairment of hippocampal MR has been linked to pathological conditions, such as depression or neurodegenerative disorders. Here, we aimed to further clarify the protective role of MR in adult hippocampal neurons by studying the survival and proliferative effects of the highly potent MR agonist fludrocortisone (Fludro) in adult rat hippocampal progenitor cells (AHPs), along with the associated signaling mechanisms. Fludro, which upregulated MR but not GR expression, increased survival and proliferation and prevented apoptosis in AHPs cultured in growth factor-deprived medium. These effects were blunted by the MR antagonist spironolactone and by high doses of the GR agonist dexamethasone. Moreover, they involved signaling through cAMP/protein kinase A (PKA)/cAMP response element-binding protein, phosphoinositide 3-kinase (PI3K)/Akt and its downstream targets glycogen synthase kinase-3beta (GSK-3beta) and mammalian target of rapamycin. Furthermore, Fludro attenuated the detrimental effects of amyloid-beta peptide 1-42 (Abeta1-42) on cell survival, proliferation, and apoptosis in AHPs, and increased the phosphorylation of both PI3K/Akt and GSK 3beta, which was reduced by Abeta1-42. Finally, Fludro blocked Abeta1-42-induced hyperphosphorylation of Tau protein, which is a main feature of Alzheimer's disease. Overall, these results are the first to show the protective and proliferative role of Fludro in AHPs, suggesting the potential therapeutic importance of targeting MR for increasing hippocampal neurogenesis and for treating neurodegenerative diseases. PMID- 27379019 TI - Signaling Interplay between Bone Marrow Adipose Tissue and Multiple Myeloma cells. AB - In the year 2000, Hanahan and Weinberg (1) defined the six Hallmarks of Cancer as: self-sufficiency in growth signals, evasion of apoptosis, insensitivity to antigrowth mechanisms, tissue invasion and metastasis, limitless replicative potential, and sustained angiogenesis. Eleven years later, two new Hallmarks were added to the list (avoiding immune destruction and reprograming energy metabolism) and two new tumor characteristics (tumor-promoting inflammation and genome instability and mutation) (2). In multiple myeloma (MM), a destructive cancer of the plasma cell that grows predominantly in the bone marrow (BM), it is clear that all these hallmarks and characteristics are in play, contributing to tumor initiation, drug resistance, disease progression, and relapse. Bone marrow adipose tissue (BMAT) is a newly recognized contributor to MM oncogenesis and disease progression, potentially affecting MM cell metabolism, immune action, inflammation, and influences on angiogenesis. In this review, we discuss the confirmed and hypothetical contributions of BMAT to MM development and disease progression. BMAT has been understudied due to technical challenges and a previous lack of appreciation for the endocrine function of this tissue. In this review, we define the dynamic, responsive, metabolically active BM adipocyte. We then describe how BMAT influences MM in terms of: lipids/metabolism, hypoxia/angiogenesis, paracrine or endocrine signaling, and bone disease. We then discuss the connection between BMAT and systemic inflammation and potential treatments to inhibit the feedback loops between BM adipocytes and MM cells that support MM progression. We aim for researchers to use this review to guide and help prioritize their experiments to develop better treatments or a cure for cancers, such as MM, that associate with and may depend on BMAT. PMID- 27379020 TI - All-Atom Structural Models of the Transmembrane Domains of Insulin and Type 1 Insulin-Like Growth Factor Receptors. AB - The receptor tyrosine kinase superfamily comprises many cell-surface receptors including the insulin receptor (IR) and type 1 insulin-like growth factor receptor (IGF1R) that are constitutively homodimeric transmembrane glycoproteins. Therefore, these receptors require ligand-triggered domain rearrangements rather than receptor dimerization for activation. Specifically, binding of peptide ligands to receptor ectodomains transduces signals across the transmembrane domains for trans-autophosphorylation in cytoplasmic kinase domains. The molecular details of these processes are poorly understood in part due to the absence of structures of full-length receptors. Using MD simulations and enhanced conformational sampling algorithms, we present all-atom structural models of peptides containing 51 residues from the transmembrane and juxtamembrane regions of IR and IGF1R. In our models, the transmembrane regions of both receptors adopt helical conformations with kinks at Pro961 (IR) and Pro941 (IGF1R), but the C terminal residues corresponding to the juxtamembrane region of each receptor adopt unfolded and flexible conformations in IR as opposed to a helix in IGF1R. We also observe that the N-terminal residues in IR form a kinked-helix sitting at the membrane-solvent interface, while homologous residues in IGF1R are unfolded and flexible. These conformational differences result in a larger tilt-angle of the membrane-embedded helix in IGF1R in comparison to IR to compensate for interactions with water molecules at the membrane-solvent interfaces. Our metastable/stable states for the transmembrane domain of IR, observed in a lipid bilayer, are consistent with a known NMR structure of this domain determined in detergent micelles, and similar states in IGF1R are consistent with a previously reported model of the dimerized transmembrane domains of IGF1R. Our all-atom structural models suggest potentially unique structural organization of kinase domains in each receptor. PMID- 27379021 TI - Fatty Infiltration of Skeletal Muscle: Mechanisms and Comparisons with Bone Marrow Adiposity. AB - Skeletal muscle and bone share common embryological origins from mesodermal cell populations and also display common growth trajectories early in life. Moreover, muscle and bone are both mechanoresponsive tissues, and the mass and strength of both tissues decline with age. The decline in muscle and bone strength that occurs with aging is accompanied in both cases by an accumulation of adipose tissue. In bone, adipocyte (AC) accumulation occurs in the marrow cavities of long bones and is known to increase with estrogen deficiency, mechanical unloading, and exposure to glucocorticoids. The factors leading to accumulation of intra- and intermuscular fat (myosteatosis) are less well understood, but recent evidence indicates that increases in intramuscular fat are associated with disuse, altered leptin signaling, sex steroid deficiency, and glucocorticoid treatment, factors that are also implicated in bone marrow adipogenesis. Importantly, accumulation of ACs in skeletal muscle and accumulation of intramyocellular lipid are linked to loss of muscle strength, reduced insulin sensitivity, and increased mortality among the elderly. Resistance exercise and whole body vibration can prevent fatty infiltration in skeletal muscle and also improve muscle strength. Therapeutic strategies to prevent myosteatosis may improve muscle function and reduce fall risk in the elderly, potentially impacting the incidence of bone fracture. PMID- 27379023 TI - Serotypes and Antibiotic Susceptibility of Streptococcus pneumoniae Isolates from Invasive Pneumococcal Disease and Asymptomatic Carriage in a Pre-vaccination Period, in Algeria. AB - In Algeria, few data is available concerning the distribution of pneumococcal serotypes and respective antibiotic resistance for the current pre-vaccination period, which is a public health concern. We identified the most frequent Streptococcus pneumoniae serogroup/types implicated in invasive pneumococcal disease (IPD; n = 80) and carriage (n = 138) in Algerian children younger than 5 years old. Serogroup/types of 78 IPD isolates were identified by capsular typing using a sequential multiplex PCR. Overall, serotypes 14, 19F, 6B, 23F, 18C, 1, 5, 7F, 19A, and 3 (55% of PCV7 serotypes, 71.3% of PCV10, and 90% of PCV13) were identified. Additionally, 7.5% of the non-vaccine serotypes 6C, 9N/L, 20, 24F, 35B, and 35F, were observed. In the case of S. pneumoniae asymptomatic children carriers, the most common serogroup/types were 6B, 14, 19F, 23F, 4, 9V/A, 1, 19A, 6A, and 3 (42.7% of PCV7 serotypes, 44.2% of PCV10, and 58% of PCV13). For 6.1% of the cases co-colonization was detected. Serotypes 14, 1, 5, and 19A were more implicated in IPD (p < 0.01), whereas serotype 6A was exclusively isolated from carriers (p < 0.01). Deaths associated with IPD were related to serotypes 19A, 14, 18C, and one non-typeable isolate. Among IPD related to vaccine serotypes, the rates of penicillin non-susceptible isolates were higher in no meningitis cases (80%) than in meningitis (66.7%), with serotypes 14, 19A, 19F, and 23F presenting the highest MIC levels (>2MUg/ml). Resistance to cefotaxime was higher in isolates from meningitis (40.5%); however, resistance to erythromycin and co trimoxazole (>40%) was more pronounced in no-meningeal forms. Overall, our results showed that PCV13 conjugate vaccine would cover up to 90% of the circulating isolates associated with IPD in Algeria, highlighting the importance of monitoring the frequency of S. pneumoniae serogroups/types during pre- and post-vaccination periods. PMID- 27379022 TI - The Role of ACTH and Corticosteroids for Sepsis and Septic Shock: An Update. AB - Sepsis is a common disorder associated with high morbidity and mortality. It is now defined as an abnormal host response to infection, resulting in life threatening dysfunction of organs. There is evidence from in vitro and in vivo experiments in various animal models and in patients that endotoxin or sepsis may directly and indirectly alter the hypothalamic-pituitary-adrenal response to severe infection. These alterations may include necrosis or hemorrhage or inflammatory mediator-mediated decreased ACTH synthesis, steroidogenesis, cortisol delivery to tissues, clearance from plasma, and decreased sensitivity of tissues to cortisol. Disruption of the hypothalamic-pituitary-adrenal axis may translate in patients with sepsis into cardiovascular and other organ dysfunction, and eventually an increase in the risk of death. Exogenous administration of corticosteroids at moderate dose, i.e., <400 mg of hydrocortisone or equivalent for >96 h, may help reversing sepsis-associated shock and organ dysfunction. Corticosteroids may also shorten the duration of stay in the ICU. Except for increased blood glucose and sodium levels, treatment with corticosteroids was rather well tolerated in the context of clinical trials. The benefit of treatment on survival remains controversial. Based on available randomized controlled trials, the likelihood of survival benefit is greater in septic shock versus sepsis patients, in sepsis with acute respiratory distress syndrome or with community-acquired pneumonia versus patients without these conditions, and in patients with a blunted cortisol response to 250 MUg of ACTH test versus those with normal response. PMID- 27379024 TI - ICEApl1, an Integrative Conjugative Element Related to ICEHin1056, Identified in the Pig Pathogen Actinobacillus pleuropneumoniae. AB - ICEApl1 was identified in the whole genome sequence of MIDG2331, a tetracycline resistant (MIC = 8 mg/L) serovar 8 clinical isolate of Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia. PCR amplification of virB4, one of the core genes involved in conjugation, was used to identify other A. pleuropneumoniae isolates potentially carrying ICEApl1. MICs for tetracycline were determined for virB4 positive isolates, and shotgun whole genome sequence analysis was used to confirm presence of the complete ICEApl1. The sequence of ICEApl1 is 56083 bp long and contains 67 genes including a Tn10 element encoding tetracycline resistance. Comparative sequence analysis was performed with similar integrative conjugative elements (ICEs) found in other members of the Pasteurellaceae. ICEApl1 is most similar to the 59393 bp ICEHin1056, from Haemophilus influenzae strain 1056. Although initially identified only in serovar 8 isolates of A. pleuropneumoniae (31 from the UK and 1 from Cyprus), conjugal transfer of ICEApl1 to representative isolates of other serovars was confirmed. All isolates carrying ICEApl1 had a MIC for tetracycline of 8 mg/L. This is, to our knowledge, the first description of an ICE in A. pleuropneumoniae, and the first report of a member of the ICEHin1056 subfamily in a non-human pathogen. ICEApl1 confers resistance to tetracycline, currently one of the more commonly used antibiotics for treatment and control of porcine pleuropneumonia. PMID- 27379025 TI - Poly-beta-hydroxybutyrate Metabolism Is Unrelated to the Sporulation and Parasporal Crystal Protein Formation in Bacillus thuringiensis. AB - Poly-3-hydroxybutyrate (PHB) is a natural polymer synthesized by many bacteria as a carbon-energy storage material. It was accumulated maximally prior to the spore formation but was degraded during the process of sporulation in Bacillus thuringiensis. Intriguingly, B. thuringiensis also accumulates large amounts of insecticidal crystal proteins (ICPs) during sporulation, which requires considerable input of carbon and energy sources. How PHB accumulation affects sporulation and ICP formation remains unclear to date. Intuitively, one would imagine that accumulated PHB provides the energy required for ICP formation. Yet our current data indicate that this is not the case. First, growth curves of the deletion mutants of phaC (encoding the PHB synthase) and phaZ (encoding the PHB depolymerase) were found to be similar to the parent strain BMB171; no difference in growth rate could be observed. In addition we further constructed the cry1Ac10 ICP gene overexpression strains of BMB171 (BMB171-cry), as well as its phaC and phaZ deletion mutants DeltaphaC-cry and DeltaphaZ-cry to compare their spore and ICP production rates. Again, not much change of ICP production was observed among these strains either. In fact, PHB was still degraded in most DeltaphaZ-cry cells as observed by transmission electron microscopy. Together these results indicated that there is no direct association between the PHB accumulation and the sporulation and ICP formation in B. thuringiensis. Some other enzymes for PHB degradation or other energy source may be responsible for the sporulation and/or ICP formation in B. thuringiensis. PMID- 27379027 TI - A Novel Treatment Protects Chlorella at Commercial Scale from the Predatory Bacterium Vampirovibrio chlorellavorus. AB - The predatory bacterium, Vampirovibrio chlorellavorus, can destroy a Chlorella culture in just a few days, rendering an otherwise robust algal crop into a discolored suspension of empty cell walls. Chlorella is used as a benchmark for open pond cultivation due to its fast growth. In nature, V. chlorellavorus plays an ecological role by controlling this widespread terrestrial and freshwater microalga, but it can have a devastating effect when it attacks large commercial ponds. We discovered that V. chlorellavorus was associated with the collapse of four pilot commercial-scale (130,000 L volume) open-pond reactors. Routine microscopy revealed the distinctive pattern of V. chlorellavorus attachment to the algal cells, followed by algal cell clumping, culture discoloration and ultimately, growth decline. The "crash" of the algal culture coincided with increasing proportions of 16s rRNA sequencing reads assigned to V. chlorellavorus. We designed a qPCR assay to predict an impending culture crash and developed a novel treatment to control the bacterium. We found that (1) Chlorella growth was not affected by a 15 min exposure to pH 3.5 in the presence of 0.5 g/L acetate, when titrated with hydrochloric acid and (2) this treatment had a bactericidal effect on the culture (2-log decrease in aerobic counts). Therefore, when qPCR results indicated a rise in V. chlorellavorus amplicons, we found that the pH-shock treatment prevented the culture crash and doubled the productive longevity of the culture. Furthermore, the treatment could be repeatedly applied to the same culture, at the beginning of at least two sequential batch cycles. In this case, the treatment was applied preventively, further increasing the longevity of the open pond culture. In summary, the treatment reversed the infection of V. chlorellavorus as confirmed by observations of bacterial attachment to Chlorella cells and by detection of V. chlorellavorus by 16s rRNA sequencing and qPCR assay. The pH-shock treatment is highly selective against prokaryotes, and it is a cost-effective treatment that can be used throughout the scale up and production process. To our knowledge, the treatment described here is the first effective control of V. chlorellavorus and will be an important tool for the microalgal industry and biofuel research. PMID- 27379028 TI - Supersaturation of Dissolved Hydrogen and Methane in Rumen of Tibetan Sheep. AB - Hydrogen (H2) is an essential substrate for methanogens to produce methane (CH4), and also influences pathways of volatile fatty acids (VFA) production in the rumen. Dissolved H2 (H2 (aq)) is the form of H2 available to microbes, and dissolved CH4 (CH4 (aq)) is important for indicating methanogens activity. Rumen H2 (aq) concentration has been estimated by assuming equilibrium with headspace gaseous H2 (H2 (g)) concentration using Henry's law, and has also been directly measured in the liquid phase in some in vitro and in vivo experiments. In this in vivo study, H2 (aq) and CH4 (aq) concentration measured directly in rumen fluid and their corresponding concentrations estimated from their gaseous phase concentrations, were compared to investigate the existence of equilibrium between the gas and liquid phases. Twenty-four Tibetan sheep were randomly assigned to two mixed diets containing the same concentrate mixed with oat grass (OG diet) or barley straw (BS diet). Rumen gaseous phase and contents were sampled using rumenocentesis and oral stomach tubing, respectively. Rumen H2 (aq) and CH4 (aq) concentration and VFA profile differed between sheep fed OG and BS diets. Measured H2 (aq) and CH4 (aq) concentration were greater than H2 (aq) and CH4 (aq) concentrations estimated using gas concentrations, indicating lack of equilibrium between gas and liquid phase and supersaturation of H2 and CH4 in rumen fluid. As a consequence, Gibbs energy changes (DeltaG) estimated for various metabolic pathways were different when calculated using dissolved gases concentrations directly measured and when using dissolved gases concentrations assuming equilibrium with the gaseous phase. Dissolved CH4, but not CH4 (g), was positively correlated with H2 (aq). Both H2 (aq) and H2 (g) concentrations were positively correlated with the molar percentage of butyrate and negatively correlated with the molar percentage of acetate. In summary, rumen fluid was supersaturated with both H2 and CH4, and H2 (aq) was closely associated with the VFA profile and CH4 (aq) concentration. The assumption of equilibrium between dissolved gases and gaseous phase affected DeltaG estimation. PMID- 27379029 TI - Acid-Tolerant Moderately Thermophilic Methanotrophs of the Class Gammaproteobacteria Isolated From Tropical Topsoil with Methane Seeps. AB - Terrestrial tropical methane seep habitats are important ecosystems in the methane cycle. Methane oxidizing bacteria play a key role in these ecosystems as they reduce methane emissions to the atmosphere. Here, we describe the isolation and initial characterization of two novel moderately thermophilic and acid tolerant obligate methanotrophs, assigned BFH1 and BFH2 recovered from a tropical methane seep topsoil habitat. The new isolates were strictly aerobic, non-motile, coccus-shaped and utilized methane and methanol as sole carbon and energy source. Isolates grew at pH range 4.2-7.5 (optimal 5.5-6.0) and at a temperature range of 30-60 degrees C (optimal 51-55 degrees C). 16S rRNA gene phylogeny placed them in a well-separated branch forming a cluster together with the genus Methylocaldum as the closest relatives (93.1-94.1% sequence similarity). The genes pmoA, mxaF, and cbbL were detected, but mmoX was absent. Strains BFH1 and BFH2 are, to our knowledge, the first isolated acid-tolerant moderately thermophilic methane oxidizers of the class Gammaproteobacteria. Each strain probably denotes a novel species and they most likely represent a novel genus within the family Methylococcaceae of type I methanotrophs. Furthermore, the isolates increase our knowledge of acid-tolerant aerobic methanotrophs and signify a previously unrecognized biological methane sink in tropical ecosystems. PMID- 27379026 TI - Genomic Microbial Epidemiology Is Needed to Comprehend the Global Problem of Antibiotic Resistance and to Improve Pathogen Diagnosis. AB - Contamination of waste effluent from hospitals and intensive food animal production with antimicrobial residues is an immense global problem. Antimicrobial residues exert selection pressures that influence the acquisition of antimicrobial resistance and virulence genes in diverse microbial populations. Despite these concerns there is only a limited understanding of how antimicrobial residues contribute to the global problem of antimicrobial resistance. Furthermore, rapid detection of emerging bacterial pathogens and strains with resistance to more than one antibiotic class remains a challenge. A comprehensive, sequence-based genomic epidemiological surveillance model that captures essential microbial metadata is needed, both to improve surveillance for antimicrobial resistance and to monitor pathogen evolution. Escherichia coli is an important pathogen causing both intestinal [intestinal pathogenic E. coli (IPEC)] and extraintestinal [extraintestinal pathogenic E. coli (ExPEC)] disease in humans and food animals. ExPEC are the most frequently isolated Gram negative pathogen affecting human health, linked to food production practices and are often resistant to multiple antibiotics. Cattle are a known reservoir of IPEC but they are not recognized as a source of ExPEC that impact human or animal health. In contrast, poultry are a recognized source of multiple antibiotic resistant ExPEC, while swine have received comparatively less attention in this regard. Here, we review what is known about ExPEC in swine and how pig production contributes to the problem of antibiotic resistance. PMID- 27379030 TI - Quantifying Limits on Replication, Death, and Quiescence of Mycobacterium tuberculosis in Mice. AB - When an individual is exposed to Mycobacterium tuberculosis (Mtb) three outcomes are possible: bacterial clearance, active disease, or latent infection. It is generally believed that most individuals exposed to Mtb become latently infected and carry the mycobacteria for life. How Mtb is maintained during this latent infection remains largely unknown. During an Mtb infection in mice, there is a phase of rapid increase in bacterial numbers in the murine lungs within the first 3 weeks, and then bacterial numbers either stabilize or increase slowly over the period of many months. It has been debated whether the relatively constant numbers of bacteria in the chronic infection result from latent (dormant, quiescent), non-replicating bacteria, or whether the observed Mtb cell numbers are due to balance between rapid replication and death. A recent study of mice, infected with a Mtb strain carrying an unstable plasmid, showed that during the chronic phase, Mtb was replicating at significant rates. Using experimental data from this study and mathematical modeling we investigated the limits of the rates of bacterial replication, death, and quiescence during Mtb infection of mice. First, we found that to explain the data the rates of bacterial replication and death could not be constant and had to decrease with time since infection unless there were large changes in plasmid segregation probability over time. While a decrease in the rate of Mtb replication with time since infection was expected due to depletion of host's resources, a decrease in the Mtb death rate was counterintuitive since Mtb-specific immune response, appearing in the lungs 3-4 weeks after infection, should increase removal of bacteria. Interestingly, we found no significant correlation between estimated rates of Mtb replication and death suggesting the decline in these rates was driven by independent mechanisms. Second, we found that the data could not be explained by assuming that bacteria do not die, suggesting that some removal of bacteria from lungs of these mice had to occur even though the total bacterial counts in these mice always increased over time. Third and finally, we showed that to explain the data the majority of bacterial cells (at least ~60%) must be replicating in the chronic phase of infection further challenging widespread belief of nonreplicating Mtb in latency. Our predictions were robust to some changes in the structure of the model, for example, when the loss of plasmid-bearing cells was mainly due to high fitness cost of the plasmid. Further studies should determine if more mechanistic models for Mtb dynamics are also able to accurately explain these data. PMID- 27379031 TI - H11/HSPB8 Restricts HIV-2 Vpx to Restore the Anti-Viral Activity of SAMHD1. AB - Virus-host interactions play vital roles in viral replication and virus-induced pathogenesis. Viruses rely entirely upon host cells to reproduce progeny viruses; however, host factors positively or negatively regulate virus replication by interacting with viral proteins. The elucidation of virus-host protein interaction not only provides a better understanding of the molecular mechanisms by which host cells combat viral infections, but also facilitates the development of new anti-viral therapeutics. Identification of relevant host factors requires techniques that enable comprehensive characterization of virus-host protein interactions. In this study, we developed a proteomic approach to systematically identify human protein kinases that interact potently with viral proteins. For this purpose, we synthesized 412 full-length human protein kinases using the wheat germ cell-free protein synthesis system, and screened them for their association with a virus protein using the amplified luminescent proximity homogenous assay (AlphaScreen). Using this system, we attempted to discover a robust anti-viral host restriction mechanism targeting virus protein X (Vpx) of HIV-2. The screen identified H11/HSPB8 as a Vpx-binding protein that negatively regulates the stability and function of Vpx. Indeed, overexpression of H11/HSPB8 promoted the degradation of Vpx via the ubiquitin-proteasome pathway and inhibited its interaction with SAMHD1, a host restriction factor responsible for blocking replication of HIV. Conversely, targeted knockdown of H11/HSPB8 in human trophoblast cells, which ordinarily express high levels of this protein, restored the expression and function of Vpx, making the cells highly susceptible to viral replication. These results demonstrate that our proteomic approach represents a powerful tool for revealing virus-host interaction not yet identified by conventional methods. Furthermore, we showed that H11/HSPB8 could be a potential host regulatory factor that may prevent placental infection of HIV-2 during pregnancy. PMID- 27379033 TI - Tracing Back Clinical Campylobacter jejuni in the Northwest of Italy and Assessing Their Potential Source. AB - Food-borne campylobacteriosis is caused mainly by the handling or consumption of undercooked chicken meat or by the ingestion of contaminated raw milk. Knowledge about the contributions of different food sources to gastrointestinal disease is fundamental to prioritize food safety interventions and to establish proper control strategies. Assessing the genetic diversity among Campylobacter species is essential to our understanding of their epidemiology and population structure. We molecularly characterized 56 Campylobacter jejuni isolates (31 from patients hospitalized with gastroenteritis, 17 from raw milk samples, and 8 from chicken samples) using multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) in order to trace the source of the disease. We also used a population genetic approach to investigate the source of the human cases from six different reservoirs of infection. MLST identified 25 different sequence types and 11 clonal complexes (CCs) (21, 658, 206, 353, 443, 48, 61, 257, 1332, 354, 574) and these included several alleles not cited previously in the PubMLST international database. The most prevalent CCs were 21, 206, and 354. PFGE showed 34 pulsotypes divided between 28 different clusters. At the fine scale, by means of PFGE and MLST, only two human cases were linked to raw milk, while one case was linked to chicken meat. The investigation revealed the presence of several genotypes among the human isolates, which probably suggests multiple foci for the infections. Finally, the source attribution model we used revealed that most cases were attributed to chicken (69.75%) as the main reservoir in Italy, followed to a lesser extent by the following sources: cattle (8.25%); environment (6.28%); wild bird (7.37%); small ruminant (5.35%), and pork (2.98%). This study confirms the importance of correlating epidemiological investigations with molecular epidemiological data to better understand the dynamics of infection. PMID- 27379032 TI - The Chromosomal parDE2 Toxin-Antitoxin System of Mycobacterium tuberculosis H37Rv: Genetic and Functional Characterization. AB - Mycobacterium tuberculosis H37Rv escapes host-generated stresses by entering a dormant persistent state. Activation of toxin-antitoxin modules is one of the mechanisms known to trigger such a state with low metabolic activity. M. tuberculosis harbors a large number of TA systems mostly located within discernible genomic islands. We have investigated the parDE2 operon of M. tuberculosis H37Rv encoding MParE2 toxin and MParD2 antitoxin proteins. The parDE2 locus was transcriptionally active from growth phase till late stationary phase in M. tuberculosis. A functional promoter located upstream of parD2 GTG start-site was identified by 5'-RACE and lacZ reporter assay. The MParD2 protein transcriptionally regulated the P parDE2 promoter by interacting through Arg16 and Ser15 residues located in the N-terminus. In Escherichia coli, ectopic expression of MParE2 inhibited growth in early stages, with a drastic reduction in colony forming units. Live-dead analysis revealed that the reduction was not due to cell death alone but due to formation of viable but non-culturable cells (VBNCs) also. The toxic activity of the protein, identified in the C-terminal residues Glu98 and Arg102, was neutralized by the antitoxin MParD2, both in vivo and in vitro. MParE2 inhibited mycobacterial DNA gyrase and interacted with the GyrB subunit without affecting its ATPase activity. Introduction of parE2 gene in the heterologous M. smegmatis host prevented growth and colony formation by the transformed cells. An M. smegmatis strain containing the parDE2 operon also switched to a non-culturable phenotype in response to oxidative stress. Loss in colony-forming ability of a major part of the MParE2 expressing cells suggests its potential role in dormancy, a cellular strategy for adaptation to environmental stresses. Our study has laid the foundation for future investigations to explore the physiological significance of parDE2 operon in mycobacterial pathogenesis. PMID- 27379034 TI - Responses of Aquatic Bacteria to Terrestrial Runoff: Effects on Community Structure and Key Taxonomic Groups. AB - Organic fertilizer application is often touted as an economical and effective method to increase soil fertility. However, this amendment may increase dissolved organic carbon (DOC) runoff into downstream aquatic ecosystems and may consequently alter aquatic microbial community. We focused on understanding the effects of DOC runoff from soils amended with compost, vermicompost, or biochar on the aquatic microbial community of a tropical reservoir. Runoff collected from a series of rainfall simulations on soils amended with different organic fertilizers was incubated for 16 days in a series of 200 L mesocosms filled with water from a downstream reservoir. We applied 454 high throughput pyrosequencing for bacterial 16S rRNA genes to analyze microbial communities. After 16 days of incubation, the richness and evenness of the microbial communities present decreased in the mesocosms amended with any organic fertilizers, except for the evenness in the mesocosms amended with compost runoff. In contrast, they increased in the reservoir water control and soil-only amended mesocosms. Community structure was mainly affected by pH and DOC concentration. Compared to the autochthonous organic carbon produced during primary production, the addition of allochthonous DOC from these organic amendments seemed to exert a stronger effect on the communities over the period of incubation. While the Proteobacteria and Actinobacteria classes were positively associated with higher DOC concentration, the number of sequences representing key bacterial groups differed between mesocosms particularly between the biochar runoff addition and the compost or vermi-compost runoff additions. The genera of Propionibacterium spp. and Methylobacterium spp. were highly abundant in the compost runoff additions suggesting that they may represent sentinel species of complex organic carbon inputs. Overall, this work further underlines the importance of studying the off site impacts of organic fertilizers as their impact on downstream aquatic systems is not negligible. PMID- 27379035 TI - Antifungal and Zearalenone Inhibitory Activity of Pediococcus pentosaceus Isolated from Dairy Products on Fusarium graminearum. AB - The present study was aimed to evaluate the bio-control efficacy of Pediococcus pentosaceus isolated from traditional fermented dairy products originated from India, against the growth and zearalenone (ZEA) production of Fusarium graminearum. The cell-free supernatants of P. pentosaceus (PPCS) were prepared and chemical profiling was carried out by GC-MS and MALDI-TOF analysis. Chemical profiling of PPCS evidenced that, the presence of phenolic antioxidants, which are responsible for the antifungal activity. Another hand, MALDI-TOF analysis also indicated the presence of antimicrobial peptides. To know the antioxidant potential of PPCS, DPPH free radical scavenging assay was carried out and IC50 value was determined as 32 +/- 1.89 MUL/mL. The antifungal activity of P. pentosaceus was determined by dual culture overlay technique and zone of inhibition was recorded as 47 +/- 2.81%, and antifungal activity of PPCS on F. graminearum was determined by micro-well dilution and scanning electron microscopic techniques. The minimum inhibitory concentration (MIC) of PPCS was determined as 66 +/- 2.18 MUL/mL in the present study. Also a clear variation in the micromorphology of mycelia treated with MIC value of PPCS compared to untreated control was documented. Further, the mechanism of growth inhibition was revealed by ergosterol analysis and determination of reactive oxygen species (ROS) in PPCS treated samples. The effects of PPCS on mycelial biomass and ZEA production were observed in a dose-dependent manner. The mechanism behind the suppression of ZEA production was studied by reverse transcriptase qPCR analysis of ZEA metabolic pathway genes (PKS4 and PKS13), and results showed that there is a dose dependent down-regulation of target gene expression in PPCS treated samples. The results of the present study were collectively proved that, the antifungal and ZEA inhibitory activity of PPCS against F. graminearum and it may find a potential application in agriculture and food industry as a natural bio controlling agent. PMID- 27379036 TI - A Bacterial Pathogen Displaying Temperature-Enhanced Virulence of the Microalga Emiliania huxleyi. AB - Emiliania huxleyi is a globally abundant microalga that plays a significant role in biogeochemical cycles. Over the next century, sea surface temperatures are predicted to increase drastically, which will likely have significant effects on the survival and ecology of E. huxleyi. In a warming ocean, this microalga may become increasingly vulnerable to pathogens, particularly those with temperature dependent virulence. Ruegeria is a genus of Rhodobacteraceae whose population size tracks that of E. huxleyi throughout the alga's bloom-bust lifecycle. A representative of this genus, Ruegeria sp. R11, is known to cause bleaching disease in a red macroalga at elevated temperatures. To investigate if the pathogenicity of R11 extends to microalgae, it was co-cultured with several cell types of E. huxleyi near the alga's optimum (18 degrees C), and at an elevated temperature (25 degrees C) known to induce virulence in R11. The algal populations were monitored using flow cytometry and pulse-amplitude modulated fluorometry. Cultures of algae without bacteria remained healthy at 18 degrees C, but lower cell counts in control cultures at 25 degrees C indicated some stress at the elevated temperature. Both the C (coccolith-bearing) and S (scale-bearing swarming) cell types of E. huxleyi experienced a rapid decline resulting in apparent death when co-cultured with R11 at 25 degrees C, but had no effect on N (naked) cell type at either temperature. R11 had no initial negative impact on C and S type E. huxleyi population size or health at 18 degrees C, but caused death in older co-cultures. This differential effect of R11 on its host at 18 and 25 degrees C suggest it is a temperature-enhanced opportunistic pathogen of E. huxleyi. We also detected caspase-like activity in dying C type cells co-cultured with R11, which suggests that programmed cell death plays a role in the death of E. huxleyi triggered by R11 - a mechanism induced by viruses (EhVs) and implicated in E. huxleyi bloom collapse. Given that E. huxleyi has recently been shown to have acquired resistance against EhVs at elevated temperature, bacterial pathogens with temperature-dependent virulence, such as R11, may become much more important in the ecology of E. huxleyi in a warming climate. PMID- 27379037 TI - Tobacco Rotated with Rapeseed for Soil-Borne Phytophthora Pathogen Biocontrol: Mediated by Rapeseed Root Exudates. AB - Black shank, caused by Phytophthora parasitica var. nicotianae, is a widespread and destructive disease of tobacco. Crop rotation is essential in controlling black shank. Here, we confirmed that rotating black shank-infested fields with rapeseed (Brassica napus) suppressed the incidence this disease. Further study demonstrated that rapeseed roots have a strong ability to attract zoospores and subsequently stop the swimming of zoospores into cystospores. Then, rapeseed roots secrete a series of antimicrobial compounds, including 2-butenoic acid, benzothiazole, 2-(methylthio)benzothiazole, 1-(4-ethylphenyl)-ethanone, and 4 methoxyindole, to inhibit the cystospore germination and mycelial growth of P. parasitica var. nicotianae. Thus, rapeseed rotated with tobacco suppresses tobacco black shank disease through the chemical weapons secreted by rapeseed roots. PMID- 27379039 TI - Enhanced Biocide Mitigation of Field Biofilm Consortia by a Mixture of D-Amino Acids. AB - Microbiologically influenced corrosion (MIC) is a major problem in the oil and gas industry as well as in many other industries. Current treatment methods rely mostly on pigging and biocide dosing. Biocide resistance is a growing concern. Thus, it is desirable to use biocide enhancers to improve the efficacy of existing biocides. D-Amino acids are naturally occurring. Our previous work demonstrated that some D-amino acids are biocide enhancers. Under a biocide stress of 50 ppm (w/w) hydroxymethyl phosphonium sulfate (THPS) biocide, 1 ppm D tyrosine and 100 ppm D-methionine used separately successfully mitigated the Desulfovibrio vulgaris biofilm on carbon steel coupons. The data reported in this work revealed that 50 ppm of an equimolar mixture of D-methionine, D-tyrosine, D leucine, and D-tryptophan greatly enhanced 50 ppm THPS biocide treatment of two recalcitrant biofilm consortia containing sulfate reducing bacteria (SRB), nitrate reducing bacteria (NRB), and fermentative bacteria, etc., from oil-field operations. The data also indicated that individual D-amino acids were inadequate for the biofilm consortia. PMID- 27379041 TI - Reconstruction of the High-Osmolarity Glycerol (HOG) Signaling Pathway from the Halophilic Fungus Wallemia ichthyophaga in Saccharomyces cerevisiae. AB - The basidiomycetous fungus Wallemia ichthyophaga grows between 1.7 and 5.1 M NaCl and is the most halophilic eukaryote described to date. Like other fungi, W. ichthyophaga detects changes in environmental salinity mainly by the evolutionarily conserved high-osmolarity glycerol (HOG) signaling pathway. In Saccharomyces cerevisiae, the HOG pathway has been extensively studied in connection to osmotic regulation, with a valuable knock-out strain collection established. In the present study, we reconstructed the architecture of the HOG pathway of W. ichthyophaga in suitable S. cerevisiae knock-out strains, through heterologous expression of the W. ichthyophaga HOG pathway proteins. Compared to S. cerevisiae, where the Pbs2 (ScPbs2) kinase of the HOG pathway is activated via the SHO1 and SLN1 branches, the interactions between the W. ichthyophaga Pbs2 (WiPbs2) kinase and the W. ichthyophaga SHO1 branch orthologs are not conserved: as well as evidence of poor interactions between the WiSho1 Src-homology 3 (SH3) domain and the WiPbs2 proline-rich motif, the absence of a considerable part of the osmosensing apparatus in the genome of W. ichthyophaga suggests that the SHO1 branch components are not involved in HOG signaling in this halophilic fungus. In contrast, the conserved activation of WiPbs2 by the S. cerevisiae ScSsk2/ScSsk22 kinase and the sensitivity of W. ichthyophaga cells to fludioxonil, emphasize the significance of two-component (SLN1-like) signaling via Group III histidine kinase. Combined with protein modeling data, our study reveals conserved and non conserved protein interactions in the HOG signaling pathway of W. ichthyophaga and therefore significantly improves the knowledge of hyperosmotic signal processing in this halophilic fungus. PMID- 27379040 TI - Streptomyces antioxidans sp. nov., a Novel Mangrove Soil Actinobacterium with Antioxidative and Neuroprotective Potentials. AB - A novel strain, Streptomyces antioxidans MUSC 164(T) was recovered from mangrove forest soil located at Tanjung Lumpur, Malaysia. The Gram-positive bacterium forms yellowish-white aerial and brilliant greenish yellow substrate mycelium on ISP 2 agar. A polyphasic approach was used to determine the taxonomy status of strain MUSC 164(T). The strain showed a spectrum of phylogenetic and chemotaxonomic properties consistent with those of the members of the genus Streptomyces. The cell wall peptidoglycan was determined to contain LL diaminopimelic acid. The predominant menaquinones were identified as MK-9(H6) and MK-9(H8), while the identified polar lipids consisted of aminolipid, diphosphatidylglycerol, glycolipid, hydroxyphosphatidylethanolamine, phospholipid, phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol and lipid. The cell wall sugars consist of galactose, glucose and ribose. The predominant cellular fatty acids (>10.0%) were identified as iso-C15: 0 (34.8%) and anteiso-C15: 0(14.0%). Phylogenetic analysis identified that closely related strains for MUSC 164(T) as Streptomyces javensis NBRC 100777(T) (99.6% sequence similarity), Streptomyces yogyakartensis NBRC 100779(T) (99.6%) and Streptomyces violaceusniger NBRC 13459(T) (99.6%). The DNA-DNA relatedness values between MUSC 164(T) and closely related type strains ranged from 23.8 +/- 0.3% to 53.1 +/- 4.3%. BOX-PCR fingerprints comparison showed that MUSC 164(T) exhibits a unique DNA profile, with DNA G + C content determined to be 71.6 mol%. Based on the polyphasic study of MUSC 164(T), it is concluded that this strain represents a novel species, for which the name Streptomyces antioxidans sp. nov. is proposed. The type strain is MUSC 164(T) (=DSM 101523(T) = MCCC 1K01590(T)). The extract of MUSC 164(T) showed potent antioxidative and neuroprotective activities against hydrogen peroxide. The chemical analysis of the extract revealed that the strain produces pyrazines and phenolic-related compounds that could explain for the observed bioactivities. PMID- 27379042 TI - Reconstructing the Genetic Potential of the Microbially-Mediated Nitrogen Cycle in a Salt Marsh Ecosystem. AB - Coastal ecosystems are considered buffer zones for the discharge of land-derived nutrients without accounting for potential negative side effects. Hence, there is an urgent need to better understand the ecological assembly and dynamics of the microorganisms that are involved in nitrogen (N) cycling in such systems. Here, we employed two complementary methodological approaches (i.e., shotgun metagenomics and quantitative PCR) to examine the distribution and abundance of selected microbial genes involved in N transformations. We used soil samples collected along a well-established pristine salt marsh soil chronosequence that spans over a century of ecosystem development at the island of Schiermonnikoog, The Netherlands. Across the examined soil successional stages, the structure of the populations of genes involved in N cycling processes was strongly related to (shifts in the) soil nitrogen levels (i.e., [Formula: see text], [Formula: see text]), salinity and pH (explaining 73.8% of the total variation, R (2) = 0.71). Quantification of the genes used as proxies for N fixation, nitrification and denitrification revealed clear successional signatures that corroborated the taxonomic assignments obtained by metagenomics. Notably, we found strong evidence for niche partitioning, as revealed by the abundance and distribution of marker genes for nitrification (ammonia-oxidizing bacteria and archaea) and denitrification (nitrite reductase nirK, nirS and nitrous oxide reductase nosZ clades I and II). This was supported by a distinct correlation between these genes and soil physico-chemical properties, such as soil physical structure, pH, salinity, organic matter, total N, [Formula: see text], [Formula: see text] and [Formula: see text], across four seasonal samplings. Overall, this study sheds light on the successional trajectories of microbial N cycle genes along a naturally developing salt marsh ecosystem. The data obtained serve as a foundation to guide the formulation of ecological models that aim to effectively monitor and manage pristine and impacted salt marsh areas. Such models should account for the ecology as well as the historical contingency of N cycling communities. PMID- 27379043 TI - Flow Cytometric Assessment of Bacterial Abundance in Soils, Sediments and Sludge. AB - Bacterial abundance is a fundamental measure in microbiology, but its assessment is often tedious, especially for soil, and sediment samples. To overcome this limitation, we adopted a time-efficient flow-cytometric (FCM) counting method involving cell detachment and separation from matrix particles by centrifugation in tubes receiving sample suspensions and Histodenz((r)) solution. We used this approach to assess bacterial abundances in diverse soils (natural and agricultural), sediments (streams and lakes) and sludge from sand-filters in a drinking water treatment plant and compared the results to bacterial abundances determined by two established methods, epifluorescence microscopy (EM) and adenosine triphosphate (ATP) quantification. Cell abundances determined by FCM and EM correlated fairly well, although absolute cell abundances were generally lower when determined by FCM. FCM also showed significant relations with cell counts converted from ATP concentrations, although estimates derived from ATP determinations were typically higher, indicating the presence of ATP sources other than bacteria. Soil and sediment organic matter (OM) content influenced the goodness of fit between counts obtained with EM and FCM. In particular, bacterial abundance determined by FCM in samples containing less than 10% OM, such as stream sediment, was particularly well correlated with the cell counts assessed by EM. Overall, these results suggest that FCM following cell detachment and purification is a useful approach to increase sample throughput for determining bacterial abundances in soils, sediments and sludge. However, notable scatter and only partial concordance among the FCM and reference methods suggests that protocols require further improvement for assessments requiring high precision, especially when OM contents in samples are high. PMID- 27379044 TI - From DNA to FBA: How to Build Your Own Genome-Scale Metabolic Model. AB - Microbiological studies are increasingly relying on in silico methods to perform exploration and rapid analysis of genomic data, and functional genomics studies are supplemented by the new perspectives that genome-scale metabolic models offer. A mathematical model consisting of a microbe's entire metabolic map can be rapidly determined from whole-genome sequencing and annotating the genomic material encoded in its DNA. Flux-balance analysis (FBA), a linear programming technique that uses metabolic models to predict the phenotypic responses imposed by environmental elements and factors, is the leading method to simulate and manipulate cellular growth in silico. However, the process of creating an accurate model to use in FBA consists of a series of steps involving a multitude of connections between bioinformatics databases, enzyme resources, and metabolic pathways. We present the methodology and procedure to obtain a metabolic model using PyFBA, an extensible Python-based open-source software package aimed to provide a platform where functional annotations are used to build metabolic models (http://linsalrob.github.io/PyFBA). Backed by the Model SEED biochemistry database, PyFBA contains methods to reconstruct a microbe's metabolic map, run FBA upon different media conditions, and gap-fill its metabolism. The extensibility of PyFBA facilitates novel techniques in creating accurate genome scale metabolic models. PMID- 27379045 TI - Two Small RNAs Conserved in Enterobacteriaceae Provide Intrinsic Resistance to Antibiotics Targeting the Cell Wall Biosynthesis Enzyme Glucosamine-6-Phosphate Synthase. AB - Formation of glucosamine-6-phosphate (GlcN6P) by enzyme GlcN6P synthase (GlmS) represents the first step in bacterial cell envelope synthesis. In Escherichia coli, expression of glmS is controlled by small RNAs (sRNAs) GlmY and GlmZ. GlmZ activates the glmS mRNA by base-pairing. When not required, GlmZ is bound by adapter protein RapZ and recruited to cleavage by RNase E inactivating the sRNA. The homologous sRNA GlmY activates glmS indirectly. When present at high levels, GlmY sequesters RapZ by an RNA mimicry mechanism suppressing cleavage of GlmZ. The interplay of both sRNAs is believed to adjust GlmS synthesis to the needs of the cell, i.e., to achieve GlcN6P homeostasis. Bacilysin (tetaine) and Nva-FMDP are dipeptide antibiotics that impair cell envelope synthesis by inhibition of enzyme GlmS through covalent modification. However, although taken up efficiently, these antibiotics are less active against E. coli for reasons unknown so far. Here we show that the GlmY/GlmZ circuit provides resistance. Inhibition of GlmS causes GlcN6P deprivation leading to activation of GlmY and GlmZ, which in turn trigger glmS overexpression in a dosage-dependent manner. Mutation of glmY or glmZ disables this response and renders the bacteria highly susceptible to GlmS inhibitors. Thus, E. coli compensates inhibition of GlmS by increasing its synthesis through the GlmY/GlmZ pathway. This mechanism is also operative in Salmonella indicating that it is conserved in Enterobacteriaceae possessing these sRNAs. As GlmY apparently responds to GlcN6P, co-application of a non-metabolizable GlcN6P analog may prevent activation of the sRNAs and thereby increase the bactericidal activity of GlmS inhibitors against wild-type bacteria. Initial experiments using glucosamine-6-sulfate support this possibility. Thus, GlcN6P analogs might be considered for co-application with GlmS inhibitors in combined therapy to treat infections caused by pathogenic Enterobacteriaceae. PMID- 27379038 TI - Global Dissemination of Carbapenemase-Producing Klebsiella pneumoniae: Epidemiology, Genetic Context, Treatment Options, and Detection Methods. AB - The emergence of carbapenem-resistant Gram-negative pathogens poses a serious threat to public health worldwide. In particular, the increasing prevalence of carbapenem-resistant Klebsiella pneumoniae is a major source of concern. K. pneumoniae carbapenemases (KPCs) and carbapenemases of the oxacillinase-48 (OXA 48) type have been reported worldwide. New Delhi metallo-beta-lactamase (NDM) carbapenemases were originally identified in Sweden in 2008 and have spread worldwide rapidly. In this review, we summarize the epidemiology of K. pneumoniae producing three carbapenemases (KPCs, NDMs, and OXA-48-like). Although the prevalence of each resistant strain varies geographically, K. pneumoniae producing KPCs, NDMs, and OXA-48-like carbapenemases have become rapidly disseminated. In addition, we used recently published molecular and genetic studies to analyze the mechanisms by which these three carbapenemases, and major K. pneumoniae clones, such as ST258 and ST11, have become globally prevalent. Because carbapenemase-producing K. pneumoniae are often resistant to most beta lactam antibiotics and many other non-beta-lactam molecules, the therapeutic options available to treat infection with these strains are limited to colistin, polymyxin B, fosfomycin, tigecycline, and selected aminoglycosides. Although, combination therapy has been recommended for the treatment of severe carbapenemase-producing K. pneumoniae infections, the clinical evidence for this strategy is currently limited, and more accurate randomized controlled trials will be required to establish the most effective treatment regimen. Moreover, because rapid and accurate identification of the carbapenemase type found in K. pneumoniae may be difficult to achieve through phenotypic antibiotic susceptibility tests, novel molecular detection techniques are currently being developed. PMID- 27379046 TI - Development of Genetic Tools for the Manipulation of the Planctomycetes. AB - Bacteria belonging to the Planctomycetes, Verrucomicrobia, Chlamydiae (PVC) superphylum are of interest for biotechnology, evolutionary cell biology, ecology, and human health. Some PVC species lack a number of typical bacterial features while others possess characteristics that are usually more associated to eukaryotes or archaea. For example, the Planctomycetes phylum is atypical for the absence of the FtsZ protein and for the presence of a developed endomembrane system. Studies of the cellular and molecular biology of these infrequent characteristics are currently limited due to the lack of genetic tools for most of the species. So far, genetic manipulation in Planctomycetes has been described in Planctopirus limnophila only. Here, we show a simple approach that allows mutagenesis by homologous recombination in three different planctomycetes species (i.e., Gemmata obscuriglobus, Gimesia maris, and Blastopirellula marina), in addition to P. limnophila, thus extending the repertoire of genetically modifiable organisms in this superphylum. Although the Planctomycetes show high resistance to most antibiotics, we have used kanamycin resistance genes in G. obscuriglobus, P. limnophila, and G. maris, and tetracycline resistance genes in B. marina, as markers for mutant selection. In all cases, plasmids were introduced in the strains by mating or electroporation, and the genetic modification was verified by Southern Blotting analysis. In addition, we show that the green fluorescent protein (gfp) is expressed in all four backgrounds from an Escherichia coli promoter. The genetic manipulation achievement in four phylogenetically diverse planctomycetes will enable molecular studies in these strains, and opens the door to developing genetic approaches not only in other planctomycetes but also other species of the superphylum, such as the Lentisphaerae. PMID- 27379047 TI - A Prospective Surveillance Study of Candidaemia: Epidemiology, Risk Factors, Antifungal Treatment and Outcome in Hospitalized Patients. AB - This study provide an up-to-date overview of the epidemiology and risk factors for Candida bloodstream infection in Scotland in 2012/2013, and the antifungal susceptibility of isolates from blood cultures from 11 National Health Service boards within Scotland. Candida isolates were identified by chromogenic agar and confirmed by MALDI-TOF methods. Survival and associated risk factors for patients stratified as albicans and non-albicans cases were assessed. Information on the spectrum of antifungals used was collected and summarized. The isolates sensitivity to different antifungals was tested by broth microdilution method and interpreted according to CLSI/EUCAST guidelines. Forty one percent of candidaemia cases were associated with Candida albicans, followed by C. glabrata (35%), C. parapsilosis (11.5%), and remainder with other Candida spp. C. albicans and C. glabrata infections were associated with 20.9 and 16.3% mortality, respectively. Survival of patients with C. albicans was significantly lower compared to non-C. albicans and catheter line removal in C. albicans patients significantly increases the survival days. Predisposing factors such as total parenteral nutrition, and number of days on mechanical ventilation or in intensive care, were significantly associated with C. albicans infections. Fluconazole was used extensively (64.5%) for treating candidaemia cases followed by echinocandins (33.8%). Based on CLSI breakpoints, MIC test found no resistance to any antifungals tested except 5.26% fluconazole resistance among C. glabrata isolates. Moreover, by comparing to EUCAST breakpoints we found 3.95% of C. glabrata isolates were resistant to anidulafungin. We have observed a shift in Candida spp. with an increasing isolation of C. glabrata. Delay and choice of antifungal treatment are associated with poor clinical outcomes. PMID- 27379048 TI - Rapid Detection of Candida albicans by Polymerase Spiral Reaction Assay in Clinical Blood Samples. AB - Candida albicans is the most common human yeast pathogen which causes mucosal infections and invasive fungal diseases. Early detection of this pathogen is needed to guide preventative and therapeutic treatment. The aim of this study was to establish a polymerase spiral reaction (PSR) assay that rapidly and accurately detects C. albicans and to assess the clinical applicability of PSR-based diagnostic testing. Internal transcribed spacer 2 (ITS2), a region between 5.8S and 28S fungal ribosomal DNA, was used as the target sequence. Four primers were designed for amplification of ITS2 with the PSR method, which was evaluated using real time turbidity monitoring and visual detection using a pH indicator. Fourteen non-C. albicans yeast strains were negative for detection, which indicated the specificity of PSR assay was 100%. A 10-fold serial dilution of C. albicans genomic DNA was subjected to PSR and conventional polimerase chain reaction (PCR) to compare their sensitivities. The detection limit of PSR was 6.9 pg/MUl within 1 h, 10-fold higher than that of PCR (69.0 pg/MUl). Blood samples (n = 122) were collected from intensive care unit and hematological patients with proven or suspected C. albicans infection at two hospitals in Beijing, China. Both PSR assay and the culture method were used to analyze the samples. Of the 122 clinical samples, 34 were identified as positive by PSR. The result was consistent with those obtained by the culture method. In conclusion, a novel and effective C. albicans detection assay was developed that has a great potential for clinical screening and point-of-care testing. PMID- 27379050 TI - Modeling the Inactivation of Intestinal Pathogenic Escherichia coli O157:H7 and Uropathogenic E. coli in Ground Chicken by High Pressure Processing and Thymol. AB - Disease causing Escherichia coli commonly found in meat and poultry include intestinal pathogenic E. coli (iPEC) as well as extraintestinal types such as the Uropathogenic E. coli (UPEC). In this study we compared the resistance of iPEC (O157:H7) to UPEC in chicken meat using High Pressure Processing (HPP) in with (the hurdle concept) and without thymol essential oil as a sensitizer. UPEC was found slightly more resistant than E. coli O157:H7 (iPEC O157:H7) at 450 and 500 MPa. A central composite experimental design was used to evaluate the effect of pressure (300-400 MPa), thymol concentration (100-200 ppm), and pressure-holding time (10-20 min) on the inactivation of iPEC O157:H7 and UPEC in ground chicken. The hurdle approach reduced the high pressure levels and thymol doses imposed on the food matrices and potentially decreased food quality damaged after treatment. The quadratic equations were developed to predict the impact (lethality) on iPEC O157:H7 (R (2) = 0.94) and UPEC (R (2) = 0.98), as well as dimensionless non linear models [Pr > F (<0.0001)]. Both linear and non-linear models were validated with data obtained from separated experiment points. All models may predict the inactivation/lethality within the same order of accuracy. However, the dimensionless non-linear models showed potential applications with parameters outside the central composite design ranges. The results provide useful information of both iPEC O157:H7 and UPEC in regard to how they may survive HPP in the presence or absence of thymol. The models may further assist regulatory agencies and food industry to assess the potential risk of iPEC O157:H7 and UPEC in ground chicken. PMID- 27379049 TI - The Dark Side of the Mushroom Spring Microbial Mat: Life in the Shadow of Chlorophototrophs. I. Microbial Diversity Based on 16S rRNA Gene Amplicons and Metagenomic Sequencing. AB - Microbial-mat communities in the effluent channels of Octopus and Mushroom Springs within the Lower Geyser Basin at Yellowstone National Park have been studied for nearly 50 years. The emphasis has mostly focused on the chlorophototrophic bacterial organisms of the phyla Cyanobacteria and Chloroflexi. In contrast, the diversity and metabolic functions of the heterotrophic community in the microoxic/anoxic region of the mat are not well understood. In this study we analyzed the orange-colored undermat of the microbial community of Mushroom Spring using metagenomic and rRNA-amplicon (iTag) analyses. Our analyses disclosed a highly diverse community exhibiting a high degree of unevenness, strongly dominated by a single taxon, the filamentous anoxygenic phototroph, Roseiflexus spp. The second most abundant organisms belonged to the Thermotogae, which have been hypothesized to be a major source of H2 from fermentation that could enable photomixotrophic metabolism by Chloroflexus and Roseiflexus spp. Other abundant organisms include two members of the Armatimonadetes (OP10); Thermocrinis sp.; and phototrophic and heterotrophic members of the Chloroflexi. Further, an Atribacteria (OP9/JS1) member; a sulfate reducing Thermodesulfovibrio sp.; a Planctomycetes member; a member of the EM3 group tentatively affiliated with the Thermotogae, as well as a putative member of the Arminicenantes (OP8) represented >=1% of the reads. Archaea were not abundant in the iTag analysis, and no metagenomic bin representing an archaeon was identified. A high microdiversity of 16S rRNA gene sequences was identified for the dominant taxon, Roseiflexus spp. Previous studies demonstrated that highly similar Synechococcus variants in the upper layer of the mats represent ecological species populations with specific ecological adaptations. This study suggests that similar putative ecotypes specifically adapted to different niches occur within the undermat community, particularly for Roseiflexus spp. PMID- 27379052 TI - Evaluation of a High-Intensity Green Fluorescent Protein Fluorophage Method for Drug- Resistance Diagnosis in Tuberculosis for Isoniazid, Rifampin, and Streptomycin. AB - A novel method for detecting drug resistance in Mycobacterium tuberculosis using mycobacteriophage Phi (2) GFP10 was evaluated with clinical isolates. The phage facilitates microscopic fluorescence detection due to the high expression of green fluorescence protein which also simplifies the operative protocol as well. A total of 128 clinical isolates were tested by the phage assay for isoniazid (INH), rifampin (RIF), and streptomycin (STR) resistance while conventional drug susceptibility test, by MGIT960, was used as reference. The sensitivities of Phi (2) GFP10 assay for INH, RIF, and STR resistance detection were 100, 98.2, and 89.3%, respectively while their specificities were 85.1, 98.6, and 95.8%, respectively. The agreement between phage and conventional assay for detecting INH, RIF, and STR resistance was 92.2, 98.4, and 93.0%, respectively. The Phi (2) GFP10-phage results could be available in 2 days for RIF and STR, while it takes 3 days for INH, with an estimated cost of less than $2 to test all the three antibiotics. The Phi (2) GFP10-phage method has the potential to be a valuable, rapid and economical screening method for detecting drug-resistant tuberculosis. PMID- 27379051 TI - Challenges in Identifying and Determining the Impacts of Infection with Pestiviruses on the Herd Health of Free Ranging Cervid Populations. AB - Although most commonly associated with the infection of domestic livestock, the replication of pestiviruses, in particular the two species of bovine viral diarrhea virus (BVDV), occurs in a wide range of free ranging cervids including white-tailed deer, mule deer, fallow deer, elk, red deer, roe deer, eland and mousedeer. While virus isolation and serologic analyses indicate that pestiviruses are circulating in these populations, little is known regarding their impact. The lack of regular surveillance programs, challenges in sampling wild populations, and scarcity of tests and vaccines compound the difficulties in detecting and controlling pestivirus infections in wild cervids. Improved detection rests upon the development and validation of tests specific for use with cervid samples and development and validation of tests that reliably detect emerging pestiviruses. Estimation of impact of pestivirus infections on herd health will require the integration of several disciplines including epidemiology, cervid natural history, veterinary medicine, pathology and microbiology. PMID- 27379053 TI - Degraded Land Restoration in Reinstating CH4 Sink. AB - Methane (CH4), a potent greenhouse gas, contributes about one third to the global green house gas emissions. CH4-assimilating microbes (mostly methanotrophs) in upland soils play very crucial role in mitigating the CH4 release into the atmosphere. Agricultural, environmental, and climatic shifts can alter CH4 sink profiles of soils, likely through shifts in CH4-assimilating microbial community structure and function. Landuse change, as forest and grassland ecosystems altered to agro-ecosystems, has already attenuated the soil CH4 sink potential, and are expected to be continued in the future. We hypothesized that variations in CH4 uptake rates in soils under different landuse practices could be an indicative of alterations in the abundance and/or type of methanotrophic communities in such soils. However, only a few studies have addressed to number and methanotrophs diversity and their correlation with the CH4 sink potential in soils of rehabilitated/restored lands. We focus on landuse practices that can potentially mitigate CH4 gas emissions, the most prominent of which are improved cropland, grazing land management, use of bio-fertilizers, and restoration of degraded lands. In this perspective paper, it is proposed that restoration of degraded lands can contribute considerably to improved soil CH4 sink strength by retrieving/conserving abundance and assortment of efficient methanotrophic communities. We believe that this report can assist in identifying future experimental directions to the relationships between landuse changes, methane assimilating microbial communities and soil CH4 sinks. The exploitation of microbial communities other than methanotrophs can contribute significantly to the global CH4 sink potential and can add value in mitigating the CH4 problems. PMID- 27379054 TI - Short-Term Heat Shock Affects Host-Virus Interaction in Mice Infected with Highly Pathogenic Avian Influenza Virus H5N1. AB - Highly pathogenic avian influenza virus (HPAIV) H5N1 is a highly contagious virus that can cause acute respiratory infections and high human fatality ratio due to excessive inflammatory response. Short-term heat shock, as a stressful condition, could induce the expression of heat shock proteins that function as molecular chaperones to protect cells against multiple stresses. However, the protective effect of short-term heat shock in influenza infection is far from being understood. In this study, mice were treated at 39 degrees C for 4 h before being infected with HPAIV H5N1. Interestingly, short-term heat shock significantly increased the levels of HSP70 and pro-inflammatory cytokines IL-6, TNF-alpha, IFN beta, and IFN-gamma in the lung tissues of mice. Following HPAIV H5N1 infection, short-term heat shock alleviated immunopathology and viral replication in lung tissue and repressed the weight loss and increased the survival rate of H5N1 infected mice. Our data reported that short-term heat shock provided beneficial anti-HPAIV H5N1 properties in mice model, which offers an alternative strategy for non-drug prevention for influenza infection. PMID- 27379056 TI - Genome Sequence of Dengue virus 3 from the Pythium insidiosum Transcriptomes. PMID- 27379057 TI - Corrigendum: Exploring the Secretomes of Microbes and Microbial Communities Using Filamentous Phage Display. AB - [This corrects the article on p. 429 in vol. 7, PMID: 27092113.]. PMID- 27379055 TI - Bifidobacteria and Their Role as Members of the Human Gut Microbiota. AB - Members of the genus Bifidobacterium are among the first microbes to colonize the human gastrointestinal tract and are believed to exert positive health benefits on their host. Due to their purported health-promoting properties, bifidobacteria have been incorporated into many functional foods as active ingredients. Bifidobacteria naturally occur in a range of ecological niches that are either directly or indirectly connected to the animal gastrointestinal tract, such as the human oral cavity, the insect gut and sewage. To be able to survive in these particular ecological niches, bifidobacteria must possess specific adaptations to be competitive. Determination of genome sequences has revealed genetic attributes that may explain bifidobacterial ecological fitness, such as metabolic abilities, evasion of the host adaptive immune system and colonization of the host through specific appendages. However, genetic modification is crucial toward fully elucidating the mechanisms by which bifidobacteria exert their adaptive abilities and beneficial properties. In this review we provide an up to date summary of the general features of bifidobacteria, whilst paying particular attention to the metabolic abilities of this species. We also describe methods that have allowed successful genetic manipulation of bifidobacteria. PMID- 27379058 TI - Colonization of the Intestinal Tract of the Polyphagous Pest Spodoptera littoralis with the GFP-Tagged Indigenous Gut Bacterium Enterococcus mundtii. AB - The alkaline gut of Lepidopterans plays a crucial role in shaping communities of bacteria. Enterococcus mundtii has emerged as one of the predominant gut microorganisms in the gastrointestinal tract of the major agricultural pest, Spodoptera littoralis. Therefore, it was selected as a model bacterium to study its adaptation to harsh alkaline gut conditions in its host insect throughout different stages of development (larvae, pupae, adults, and eggs). To date, the mechanism of bacterial survival in insects' intestinal tract has been unknown. Therefore, we have engineered a GFP-tagged species of bacteria, E. mundtii, to track how it colonizes the intestine of S. littoralis. Three promoters of different strengths were used to control the expression of GFP in E. mundtii. The promoter ermB was the most effective, exhibiting the highest GFP fluorescence intensity, and hence was chosen as our main construct. Our data show that the engineered fluorescent bacteria survived and proliferated in the intestinal tract of the insect at all life stages for up to the second generation following ingestion. PMID- 27379059 TI - Photodynamic Inactivation of Root Canal Bacteria by Light Activation through Human Dental Hard and Simulated Surrounding Tissue. AB - INTRODUCTION: Photodynamic inactivation of bacteria (PIB) may be a supportive antimicrobial approach for use in endodontics, but sufficient activation of photosensitizers (PS) in root canals is a critical point. Therefore, aim of this study was to evaluate the ability of PS absorbing blue (TMPyP) or red light (Methylene Blue; MB) for light activation through human dental hard and simulated surrounding tissue to inactivate root canal bacteria. METHODS: A tooth model was fabricated with a human premolar and two molars in an acrylic resin bloc simulating the optical properties of a porcine jaw. The distal root canal of the first molar was enlarged to insert a glass tube (external diameter 2 mm) containing PS and stationary-phase Enterococcus faecalis. Both PS (10 MUM) were irradiated for 120 s with BlueV (20 mW/cm(2); lambdaem = 400-460 nm) or PDT 1200L (37.8 mW/cm(2); lambdaem = 570-680 nm; both: Waldmann Medizintechnik), respectively. Irradiation parameters ensured identical numbers of photons absorbed by each PS. Three setups were chosen: irradiating the glass pipette only (G), the glass pipette inside the single tooth without (GT) and with (GTM) simulated surrounding tissues. Colony forming units (CFU) were evaluated. Transmission measurements of the buccal halves of hemisected mandibular first molars were performed by means of a photospectrometer. RESULTS: PIB with both PS led to reduction by >= 5 log10 of E. faecalis CFU for each setup. From transmission measurements, a threshold wavelength lambdath for allowing an amount of light transmission for sufficient activation of PS was determined to be 430 nm. CONCLUSION: This study can be seen as proof of principle that light activation of given intra-canal PS from outside a tooth may be possible at wavelengths >= 430 nm, facilitating clinical application of PIB in endodontics. PMID- 27379060 TI - Yeast Biodiversity from DOQ Priorat Uninoculated Fermentations. AB - Climate, soil, and grape varieties are the primary characteristics of terroir and lead to the definition of various appellations of origin. However, the microbiota associated with grapes are also affected by these conditions and can leave a footprint in a wine that will be part of the characteristics of terroir. Thus, a description of the yeast microbiota within a vineyard is of interest not only to provide a better understanding of the winemaking process, but also to understand the source of microorganisms that maintain a microbial footprint in wine from the examined vineyard. In this study, two typical grape varieties, Grenache and Carignan, have been sampled from four different vineyards in the DOQ Priorat winegrowing region. Afterward, eight spontaneous alcoholic fermentations containing only grapes from one sampling point and of one variety were conducted at laboratory scale. The fermentation kinetics and yeast population dynamics within each fermentation experiment were evaluated. Yeast identification was performed by RFLP-PCR of the 5.8S-ITS region and by sequencing D1/D2 of the 26S rRNA gene of the isolates. The fermentation kinetics did not indicate clear differences between the two varieties of grapes or among vineyards. Approximately 1,400 isolates were identified, exhibiting high species richness in some fermentations. Of all the isolates studied, approximately 60% belong to the genus Hanseniaspora, 16% to Saccharomyces, and 11% to Candida. Other minor genera, such as Hansenula, Issatchenkia, Kluyveromyces, Saccharomycodes, and Zygosaccharomyces, were also found. The distribution of the identified yeast throughout the fermentation process was studied, and Saccharomyces cerevisiae was found to be present mainly at the end of the fermentation process, while Aureobasidium pullulans was isolated primarily during the first days of fermentation in three of the eight spontaneous fermentations. This work highlights the complexity and diversity of the vineyard ecosystem, which contains yeasts from different species. The description of this yeast diversity will lead to the selection of native microbiota that can be used to produce quality wines with the characteristics of the Priorat. PMID- 27379061 TI - Siderophore Biosynthesis but Not Reductive Iron Assimilation Is Essential for the Dimorphic Fungus Nomuraea rileyi Conidiation, Dimorphism Transition, Resistance to Oxidative Stress, Pigmented Microsclerotium Formation, and Virulence. AB - Iron is an indispensable factor for the dimorphic insect pathogenic Nomuraea rileyi to form persistent microsclerotia which can replace conidia or blastospores for commercial mass production. There are two high affinity iron acquisition pathways in N. rileyi, siderophore-assisted iron mobilization and reductive iron assimilation systems. Transcription of the two iron uptake pathways related genes is induced under iron-limiting conditions. Stage-specific iron uptake-related genes expression during microsclerotia development shows siderophore-mediated iron acquisition genes are rigorously upregulated specifically during the formation and mature period while reductive iron assimilation related genes just display a higher expression at the late maturation period. Abrogation of reductive iron assimilation, by the deletion of the high affinity iron permease (NrFtrA), has no visible effect on microsclerotia biogenesis in N. rileyi. In sharp contrast, N. rileyi L-ornithine-N(5) monooxygenase (NrSidA), required for synthesis of all siderophores, is absolutely necessary for the development of pigmented microsclerotia. In agreement with the lower intracellular iron contents of microsclerotia in DeltaNrSidA strains, not only the pigments, but both the number and the biomass are also noticeably reduced. Certain concentration of ROS is required for promoting microsclerotia biogenesis. Combined with expression pattern analysis of related genes and quantitative of intracellular iron or extracellular siderophore in WT and mutants, these data demonstrate the lack of adequate intracellular iron caused by the loss of the siderophore results in the deficiency of ROS detoxication. Furthermore, DeltaNrSidA strains show significantly increased sensitivity to hydrogen peroxide. Besides, NrSidA, but not NrFtrA, play a crucial role in vegetative growth under iron-limiting conditions, conidiation, and dimorphic switching. Remarkably, the slower growth of the DeltaNrSidA strains in vivo due to a reduced capacity for iron acquisition leads to the loss of virulence in Spodoptera litura while the DeltaNrFtrA mutants behaved as WT during infection. Together, these results prove siderophore-assisted iron mobilization is the major pathway of cellular iron uptake and essential for conidiation, dimorphism transition, oxidative stress resistance, pigmented microsclerotium formation and full virulence. PMID- 27379062 TI - Synergistic Cellulose Hydrolysis Dominated by a Multi-Modular Processive Endoglucanase from Clostridium cellulosi. AB - Recalcitrance of biomass feedstock remains a challenge for microbial conversion of lignocellulose into biofuel and biochemicals. Clostridium cellulosi, one thermophilic bacterial strain dominated in compost, could hydrolyze lignocellulose at elevated temperature by secreting more than 38 glycoside hydrolases belong to 15 different families. Though one multi-modular endoglucanase CcCel9A has been identified from C. cellulosi CS-4-4, mechanism of synergistic degradation of cellulose by various cellulases from strain CS-4-4 remains elusive. In this study, CcCel9A, CcCel9B, and CcCel48A were characterized as processive endoglucanase, non-processive endoglucanase, and exoglucanase, respectively. To understand how they cooperate with each other, we estimated the approximate concentration ratio on the zymogram and optimized it using purified enzymes in vitro. Synergism between individual glycoside hydrolase during cellulose hydrolysis in the mixture was observed. CcCel9A and CcCel48A could degrade cellulose chain from non-reducing ends and reducing ends, respectively, to cello-oligosaccharide. CcCel9B could cut cellulose chain randomly and cello oligosaccharides with varied length were released. In addition, a beta glucosidase BlgA from Caldicellulosiruptor sp. F32 which could cleave cello oligosaccharides including G2-G6 to glucose was added to the enzyme mixture to remove the product inhibition of its partners. The combination and ratios of these cellulases were optimized based on the release rate of glucose. Hydrolysis of corn stalk was conducted by a four-component cocktail (CcCel9A:CcCel9B:CcCel48A:BlgA = 25:25:10:18), and only glucose was detected as main production by using high-performance anion-exchange chromatography. Processive endoglucanase CcCel9A, dominated in secretome of C. cellulosi, showed good potential in developing cellulase cocktail due to its exquisite cooperation with various cellulases. PMID- 27379063 TI - Indirect Evidence Link PCB Dehalogenation with Geobacteraceae in Anaerobic Sediment-Free Microcosms. AB - Although polychlorinated biphenyls (PCBs) production was brought to a halt 30 years ago, recalcitrance to degradation makes them a major environmental pollutant at a global scale. Previous studies confirmed that organohalide respiring bacteria (OHRB) were capable of utilizing chlorinated congeners as electron acceptor. OHRB belonging to the Phyla Chloroflexi and Firmicutes are nowadays considered as the main PCB-dechlorinating organisms. In this study, we aimed at exploring the involvement of other taxa in PCB dechlorination using sediment-free microcosms (SFMs) and the Delor PCB mixture. High rates of congener dehalogenation (up to 96%) were attained in long-term incubations of up to 692 days. Bacterial communities were dominated by Chloroflexi, Proteobacteria, and Firmicutes, among strictly simplified community structures composed of 12 major phyla only. In a first batch of SFMs, Dehalococcoides mccartyi closely affiliated with strains CG4 and CBDB1 was considered as the main actor associated with congener dehalogenation. Addition of 2-bromoethanesulfonate (BES), a known inhibitor of methanogenic activity in a second batch of SFMs had an adverse effect on the abundance of Dehalococcoides sp. Only two sequences affiliated to this Genus could be detected in two (out of six) BES-treated SFMs, contributing to a mere 0.04% of the communities. BES-treated SFMs showed very different community structures, especially in the contributions of organisms involved in fermentation and syntrophic activities. Indirect evidence provided by both statistical and phylogenetic analysis validated the implication of a new cluster of actors, distantly affiliated with the Family Geobacteraceae (Phylum delta Proteobacteria), in the dehalogenation of low chlorinated PCB congeners. Members of this Family are known already for their dehalogenation capacity of chlorinated solvents. As a result, the present study widens the knowledge for the phylogenetic reservoir of indigenous PCB dechlorinating taxa. PMID- 27379064 TI - SLPW: A Virulent Bacteriophage Targeting Methicillin-Resistant Staphylococcus aureus In vitro and In vivo. AB - Staphylococcus aureus (S. aureus) is a Gram-positive pathogen causing a variety of infections in humans and animals. Extensive use of antibiotics has led to the emergence of methicillin-resistant S. aureus (MRSA). As an alternative antibacterial agent against drug-resistant S. aureus, a lytic phage, designated SLPW, was isolated from fecal sewage in a pig farm. The SLPW was morphologically classified under Podoviridae and contains a double-stranded DNA genome. The genome of SLPW was 17,861 bp (29.35% G+C) containing 20 open reading frames and lacked regions encoding lysogeny-related integrase gene and cI repressor gene. Phage SLPW showed a broad host range and high efficiency of plating against various types of S. aureus. One-step growth curve showed a short latency period (10 min) and a long lytic period (120 min). Phage SLPW remained stable under a wide range of temperatures or pH and was almost unaffected in chloroform or ultraviolet light. Further, it efficiently lysed MRSA strains in vitro and in vivo. Intraperitoneal phage administration at 1 h post-infection cured the mice and reduced the bacterial expression of inflammatory cytokines in mice. Specifically, the phage SLPW displayed a wide antibacterial spectrum. It was therapeutically effective against intra-abdominal infection in mice harboring different multilocus sequence typing (MLST) types of S. aureus strains. Therefore, phage SLPW is a potential therapeutic agent against MRSA infections. PMID- 27379065 TI - Multi-Drug Resistance Mediated by Class 1 Integrons in Aeromonas Isolated from Farmed Freshwater Animals. AB - Aeromonas is regarded as an important pathogen of freshwater animals but little is known about the genetics of its antimicrobial resistance in Chinese aquaculture. The aim of this study was to investigate the presence of integrons and characterize multidrug resistant Aeromonas spp. isolated from diseased farmed freshwater animals. These animal samples included fish, ornamental fish, shrimp, turtles, and amphibians which were collected from 64 farms in Guangdong province of South China. One hundred and twelve Aeromonas spp. isolates were examined for antimicrobial resistance phenotypes and the presence of class 1 integron sequences. Twenty-two (19.6%) of these isolates carried a class 1 integron comprising six different gene insertion cassettes including drfA12-orfF-aadA2, drfA12-orfF, aac(6')-II-bla OXA-21 -cat3, catB3, arr-3, and dfrA17. Among these, drfA12-orfF-aadA2 was the dominant gene cassette array (63.6%, 14/22) and this is the first report of aac(6')-II-bla OXA-21 -cat3 in an Aeromonas hydrophila isolate from a Chinese giant salamander (Andrias davidianus). All the integron positive strains were resistant to more than five agents and 22 contained other resistance genes including bla CTX-M-3, bla TEM-1, aac(6')-Ib-cr, and tetA. All integron-positive isolates also contained mutations in the quinolone resistance determining regions (QRDR). Our investigation demonstrates that freshwater animals can serve as a reservoir for pathogenic Aeromonas strains containing multiple drug-resistance integrons. This data suggests that surveillance for antimicrobial resistance of animal origin and a prudent and responsible use of antimicrobials in aquaculture is necessary in these farms. PMID- 27379066 TI - Composition and Functional Characterization of Microbiome Associated with Mucus of the Coral Fungia echinata Collected from Andaman Sea. AB - This study describes the community composition and functions of the microbiome associated with the mucus of the coral Fungia echinata based on metagenomic approach. Metagenome sequence data showed a dominance of the class Gammaproteobacteria followed by Alphaproteobacteria, Betaproteobacteria, Deltaproteobacteria, Flavobacteriia, Bacilli, and Clostridia. At the order level, the most abundant groups were Pseudomonadales, Oceanospirillales, Alteromonadales, and Rhodobacterales. The genus Psychrobacter was the most predominant followed by Thalassolituus and Cobetia, although other genera were also present, such as Sulfitobacter, Pseudoalteromonas, Oleispira, Halomonas, Oceanobacter, Acinetobacter, Pseudomonas, Vibrio, and Marinobacter. The metabolic profile of the bacterial community displayed high prevalence of genes associated with core-housekeeping processes, such as carbohydrates, amino acids, proteins, and nucleic acid metabolism. Further, high abundance of genes coding for DNA replication and repair, stress response, and virulence factors in the metagenome suggested acquisition of specific environmental adaptation by the microbiota. Comparative analysis with other coral metagenome exhibits marked differences at the taxonomical and functional level. This study suggests the bacterial community compositions are influenced by the specific coral micro-niche and the oligotrophic marine environment. PMID- 27379067 TI - Contribution of Two Different Packaging Material to Microbial Contamination of Peaches: Implications in Their Microbiological Quality. AB - AIM: AIM of this work was understanding the microbial transfer dynamics from packaging to packed peaches in relation to the packaging used. METHOD AND RESULTS: A challenge test was performed, inoculating Escherichia coli, Pseudomonas spp. and Saccharomyces cerevisiae on cardboards and RPC (Reusable Plastic Containers), and monitoring their cell loads on fruits according to a probabilistic model and a Response Surface Methodology (RSM) in relation to several independent variables (number of fruit lesions, fruit temperature storage and commercialization time). The data recorded on packed peaches for Pseudomonas and S. cerevisiae were modeled to fit the second order model to study the main, interactive and quadratic effects of the independent variables on the cell loads of target microorganisms as well as on the shelf-life of the fruits in relation to packaging material used. The data collected for E. coli were codified as presence (1) or absence (0) and modeled with a logistic regression analysis to assess the probability of E. coli transferring from packaging to fruits in relation to the adopted variables. The data showed a higher contamination frequency of the fruits packed in plastic than in cardboard. Increasing the storage temperature and the number of lesions, the probability of transferring of E. coli from packaging materials to fruits increased, independently on commercialization time or packaging used. For Pseudomonas, the contamination levels detected on fruits packaged in plastic were significantly higher compared to those found on fruits packed in cardboard, independently on the considered variables. The polynomial equations showed the S. cerevisiae cell loads of fruits stored in plastic was positively affected by the quadratic term of temperature. CONCLUSIONS: the use of cardboard, compared to plastic, can significantly reduce the potential of microbial transferring from packaging to fruits. The probabilistic and kinetic models used showed a higher microbiological qualities of peaches stored in cardboard boxes, independently on the independent variables considered. The best performances of cardboard, compared to plastic, was probably due to its capability to entrap microbial cells. SIGNIFICANCE AND IMPACT: cardboard reduces fruit contamination and increases their shelf-life with positive fallouts on fruit shelf-life and all the logistic and distribution chain. PMID- 27379068 TI - Arbuscular Mycorrhizal Fungal Hyphae Alter Soil Bacterial Community and Enhance Polychlorinated Biphenyls Dissipation. AB - We investigated the role of arbuscular mycorrhizal fungal (AMF) hyphae in alternation of soil microbial community and Aroclor 1242 dissipation. A two compartment rhizobox system with double nylon meshes in the central was employed to exclude the influence of Cucurbita pepo L. root exudates on hyphal compartment soil. To assess the quantitative effect of AMF hyphae on soil microbial community, we separated the hyphal compartment soil into four horizontal layers from the central mesh to outer wall (e.g., L1-L4). Soil total PCBs dissipation rates ranged from 35.67% of L4 layer to 57.39% of L1 layer in AMF inoculated treatment, which were significant higher than the 17.31% of the control (P < 0.05). The dissipation rates of tri-, tetrachlorinated biphenyls as well as the total PCBs were significantly correlated with soil hyphal length (P < 0.01). Real time quantitative PCR results indicated that the Rhodococcus-like bphC gene was 2 3 orders of magnitude more than that of Pseudomonas-like bphC gene, and was found responded positively to AMF. Phylogenetic analyses of the 16S rDNA sequenced by the Illumina Miseq sequencing platform indicated that AMF hyphae altered bacterial community compositions. The phylum Betaproteobacteria and Actinobacteria were dominated in the soil, while Burkholderiales and Actinomycetales were dominated at the order level. Taxa from the Comamonadaceae responded positively to AMF and trichlorinated biphenyl dissipation, while taxa from the Oxalobacteraceae and Streptomycetaceae responded negatively to AMF and PCB congener dissipation. Our results suggested that the AMF hyphal exudates as well as the hyphae per se did have quantitative effects on shaping soil microbial community, and could modify the PCBs dissipation processes consequently. PMID- 27379069 TI - Identification of Candida haemulonii Complex Species: Use of ClinProTools(TM) to Overcome Limitations of the Bruker Biotyper(TM), VITEK MS(TM) IVD, and VITEK MS(TM) RUO Databases. AB - Candida haemulonii is now considered a complex of two species and one variety: C. haemulonii sensu stricto, Candida duobushaemulonii and the variety C. haemulonii var. vulnera. Identification (ID) of these species is relevant for epidemiological purposes and for therapeutic management, but the different phenotypic commercial systems are unable to provide correct species ID for these emergent pathogens. Hence, we evaluated the MALDI-TOF MS performance for the ID of C. haemulonii species, analyzing isolates/strains of C. haemulonii complex species, Candida pseudohaemulonii and Candida auris by two commercial platforms, their databases and softwares. To differentiate C. haemulonii sensu sctricto from the variety vulnera, we used the ClinProTools(TM) models and a single-peak analysis with the software FlexAnalysis(TM). The Biotyper(TM) database gave 100% correct species ID for C. haemulonii sensu stricto, C. pseudohaemulonii and C. auris, with 69% of correct species ID for C. duobushaemulonii. Vitek MS(TM) IVD database gave 100% correct species ID for C. haemulonii sensu stricto, misidentifying all C. duobushaemulonii and C. pseudohaemulonii as C. haemulonii, being unable to identify C. auris. The Vitek MS(TM) RUO database needed to be upgraded with in-house SuperSpectra to discriminate C. haemulonii sensu stricto, C. duobushaemulonii, C. pseudohaemulonii, and C. auris strains/isolates. The generic algorithm model from ClinProTools(TM) software showed recognition capability of 100% and cross validation of 98.02% for the discrimination of C. haemulonii sensu stricto from the variety vulnera. Single-peak analysis showed that the peaks 5670, 6878, or 13750 m/z can distinguish C. haemulonii sensu stricto from the variety vulnera. PMID- 27379071 TI - Rapid Detection and Isolation of Escherichia coli O104:H4 from Milk Using Monoclonal Antibody-coated Magnetic Beads. AB - Monoclonal antibodies (MAbs) specific for the lipopolysaccharide (LPS) of Escherichia coli O104:H4 were produced by fusion of Sp2/O-Ag-14 mouse myeloma cells with spleen cells of Balb/c mice, immunized with heat-inactivated and sonicated E. coli O104:H4 bacterial cells. Four MAbs specific for the E. coli O104:H4 LPS (1E6G6, 1F4C9, 3G6G7, and 4G10D2) were characterized and evaluated for the use in a method for the detection of E. coli O104:H4 in milk samples that involves antibody conjugation to magnetic microbeads to reduce time and increase the efficiency of isolation. MAb 1E6G6 was selected and coupled to microbeads, then used for immuno-magnetic separation (IMS); the efficiency of the IMS method for E. coli O104:H4 isolation from milk was evaluated and compared to that of the EU RL VTEC conventional culture-based isolation procedure. Milk suspensions also containing other pathogenic bacteria that could potentially be found in milk (Campylobacter jejuni, Listeria monocytogenes, and Staphylococcus aureus) were also tested to evaluate the specificity of MAb-coated beads. Beads coated with MAb 1E6G6 showed a good ability to capture the E. coli O104:H4, even in milk samples contaminated with other bacteria, with a higher number of E. coli O104:H4 CFU reisolated in comparison with the official method (121 and 41 CFU, respectively, at 10(3) E. coli O104:H4 initial load; 19 and 6 CFU, respectively, at 10(2) E. coli O104:H4 initial load; 1 and 0 CFU, respectively, at 10(1) E. coli O104:H4 initial load). The specificity was 100%. PMID- 27379070 TI - Diversity and Distribution of Prokaryotes within a Shallow-Water Pockmark Field. AB - Pockmarks are crater-like depression on the seafloor associated with hydrocarbon ascent through muddy sediments in continental shelves around the world. In this study, we examine the diversity and distribution of benthic microbial communities at shallow-water pockmarks adjacent to the Middle Adriatic Ridge. We integrate microbial diversity data with characterization of local hydrocarbons concentrations and sediment geochemistry. Our results suggest these pockmarks are enriched in sedimentary hydrocarbons, and host a microbial community dominated by Bacteria, even in deeper sediment layers. Pockmark sediments showed higher prokaryotic abundance and biomass than surrounding sediments, potentially due to the increased availability of organic matter and higher concentrations of hydrocarbons linked to pockmark activity. Prokaryotic diversity analyses showed that the microbial communities of these shallow-water pockmarks are unique, and comprised phylotypes associated with the cycling of sulfur and nitrate compounds, as well as numerous know hydrocarbon degraders. Altogether, this study suggests that shallow-water pockmark habitats enhance the diversity of the benthic prokaryotic biosphere by providing specialized environmental niches. PMID- 27379072 TI - Simultaneous Alcoholic and Malolactic Fermentations by Saccharomyces cerevisiae and Oenococcus oeni Cells Co-immobilized in Alginate Beads. AB - Malolactic fermentation (MLF) usually takes place after the end of alcoholic fermentation (AF). However, the inoculation of lactic acid bacteria together with yeast starter cultures is a promising system to enhance the quality and safety of wine. In recent years, the use of immobilized cell systems has been investigated, with interesting results, for the production of different fermented foods and beverages. In this study we have carried out the simultaneous immobilization of Saccharomyces cerevisiae and Oenococcus oeni in alginate beads and used them in microvinifications tests to produce Negroamaro wine. The process was monitored by chemical and sensorial analyses and dominance of starters and cell leaking from beads were also checked. Co-immobilization of S. cerevisiae and O. oeni allowed to perform an efficient fermentation process, producing low volatile acidity levels and ethanol and glycerol concentrations comparable with those obtained by cell sequential inoculum and co-inoculum of yeast and bacteria cells in free form. More importantly, co-immobilization strategy produced a significant decrease of the time requested to complete AF and MLF. The immobilized cells could be efficiently reused for the wine fermentation at least three times without any apparent loss of cell metabolic activities. This integrated biocatalytic system is able to perform simultaneously AF and MLF, producing wines similar in organoleptic traits in comparison with wines fermented following traditional sequential AF and MLF with free cell starters. The immobilized-cell system, that we here describe for the first time in our knowledge, offers many advantages over conventional free cell fermentations, including: (i) elimination of non-productive cell growth phases; (ii) feasibility of continuous processing; (iii) re-use of the biocatalyst. PMID- 27379073 TI - Corrigendum: Leishmanicidal Activity of Piper nigrum Bioactive Fractions is Interceded via Apoptosis In Vitro and Substantiated by Th1 Immunostimulatory Potential In Vivo. AB - [This corrects the article on p. 1368 in vol. 6, PMID: 26696979.]. PMID- 27379074 TI - Bovine Viral Diarrhea Virus (BVDV) in White-Tailed Deer (Odocoileus virginianus). AB - Bovine viral diarrhea virus (BVDV) is the prototypic member of the genus Pestivirus in the family Flaviviridae. Infections with BVDV cause substantial economic losses to the cattle industries, prompting various organized control programs in several countries. In North America, these control programs are focused on the identification and removal of persistently infected (PI) cattle, enhancement of BVDV-specific immunity through vaccination, and the implementation of biosecure farming practices. To be successful, control measures must be based on complete knowledge of the epidemiology of BVDV, including the recognition of other potential sources of the virus. BVDV does not possess strict host specificity, and infections of over 50 species in the mammalian order Artiodactyla have been reported. Over 50 years ago, serologic surveys first suggested the susceptibility of white-tailed deer (Odocoileus virginianus), the most abundant free-ranging ruminant in North America, to BVDV. However, susceptibility of white-tailed deer to BVDV infection does not alone imply a role in the epidemiology of the virus. To be a potential wildlife reservoir, white tailed deer must: (1) be susceptible to BVDV, (2) shed BVDV, (3) maintain BVDV in the population, and (4) have sufficient contact with cattle that allow spillback infections. Based on the current literature, this review discusses the potential of white-tailed deer to be a reservoir for BVDV. PMID- 27379075 TI - A Synthetic Ecology Perspective: How Well Does Behavior of Model Organisms in the Laboratory Predict Microbial Activities in Natural Habitats? AB - In this perspective article, we question how well model organisms, the ones that are easy to cultivate in the laboratory and that show robust growth and biomass accumulation, reflect the dynamics and interactions of microbial communities observed in nature. Today's -omics toolbox allows assessing the genomic potential of microbes in natural environments in a high-throughput fashion and at a strain level resolution. However, understanding of the details of microbial activities and of the mechanistic bases of community function still requires experimental validation in simplified and fully controlled systems such as synthetic communities. We have studied methane utilization in Lake Washington sediment for a few decades and have identified a number of species genetically equipped for this activity. We have also identified co-occurring satellite species that appear to form functional communities together with the methanotrophs. Here, we compare experimental findings from manipulation of natural communities involved in metabolism of methane in this niche with findings from manipulation of synthetic communities assembled in the laboratory of species originating from the same study site, from very simple (two-species) to rather complex (50-species) synthetic communities. We observe some common trends in community dynamics between the two types of communities, toward representation of specific functional guilds. However, we also identify strong discrepancies between the dominant methane oxidizers in synthetic communities compared to natural communities, under similar incubation conditions. These findings highlight the challenges that exist in using the synthetic community approach to modeling dynamics and species interactions in natural communities. PMID- 27379076 TI - Mild Nutrient Starvation Triggers the Development of a Small-Cell Survival Morphotype in Mycobacteria. AB - Mycobacteria, generally believed to be non-sporulating, are well known to survive shock starvation in saline for extended periods of time in a non-replicating state without any apparent morphological changes. Here, we uncover that mycobacteria can undergo cellular differentiation by exposing Mycobacterium smegmatis to mild starvation conditions. Traces of various carbon sources in saline triggered the development of a novel small resting cell (SMRC) morphotype. Development of SMRCs could also be observed for other mycobacteria, suggesting evolutionary conservation of this differentiation pathway. Fluorescence microscopic analyses showed that development of SMRCs progresses via septated, multi-nucleoided cell intermediates, which divide to generate mono-nucleoided SMRCs. Intriguingly, saline shock-starved large resting cells (LARCs), which did not show cell size or surface changes when observed by scanning electron microscopy, remodeled their internal structure to septated, multi-nucleoided cells, similar to the intermediates seen during differentiation to SMRCs. Our results suggest that mycobacteria harbor a starvation-induced differentiation program in which at first septated, multi-nucleoided cells are generated. Under zero-nutrient conditions bacteria terminate development at this stage as LARCs. In the presence of traces of a carbon source, these multi-nucleoided cells continue differentiation into mono-nucleoided SMRCs. Both SMRCs and LARCs exhibited extreme antibiotic tolerance. SMRCs showed increased long-term starvation survival, which was associated with the presence of lipid inclusion bodies. PMID- 27379077 TI - Corrigendum: Survey and Visual Detection of Zaire Ebolavirus in Clinical Samples Targeting the Nucleoprotein Gene in Sierra Leone. AB - [This corrects the article on p. 1332 in vol. 6, PMID: 26648918.]. PMID- 27379078 TI - Prediction of Biofilm Inhibiting Peptides: An In silico Approach. AB - Approximately 75% of microbial infections found in humans are caused by microbial biofilms. These biofilms are resistant to host immune system and most of the currently available antibiotics. Small peptides are extensively studied for their role as anti-microbial peptides, however, only a limited studies have shown their potential as inhibitors of biofilm. Therefore, to develop a unique computational method aimed at the prediction of biofilm inhibiting peptides, the experimentally validated biofilm inhibiting peptides sequences were used to extract sequence based features and to identify unique sequence motifs. Biofilm inhibiting peptides were observed to be abundant in positively charged and aromatic amino acids, and also showed selective abundance of some dipeptides and sequence motifs. These individual sequence based features were utilized to construct Support Vector Machine-based prediction models and additionally by including sequence motifs information, the hybrid models were constructed. Using 10-fold cross validation, the hybrid model displayed the accuracy and Matthews Correlation Coefficient (MCC) of 97.83% and 0.87, respectively. On the validation dataset, the hybrid model showed the accuracy and MCC value of 97.19% and 0.84, respectively. The validated model and other tools developed for the prediction of biofilm inhibiting peptides are available freely as web server at http://metagenomics.iiserb.ac.in/biofin/ and http://metabiosys.iiserb.ac.in/biofin/. PMID- 27379079 TI - Genome Analysis of Thermosulfurimonas dismutans, the First Thermophilic Sulfur Disproportionating Bacterium of the Phylum Thermodesulfobacteria. AB - Thermosulfurimonas dismutans S95(T), isolated from a deep-sea hydrothermal vent is the first bacterium of the phylum Thermodesulfobacteria reported to grow by the disproportionation of elemental sulfur, sulfite, or thiosulfate with carbon dioxide as the sole carbon source. In contrast to its phylogenetically close relatives, which are dissimilatory sulfate-reducers, T. dismutans is unable to grow by sulfate respiration. The features of this organism and its 2,1 Mb draft genome sequence are described in this report. Genome analysis revealed that the T. dismutans genome contains the set of genes for dissimilatory sulfate reduction including ATP sulfurylase, the AprA and B subunits of adenosine-5'-phosphosulfate reductase, and dissimilatory sulfite reductase. The oxidation of elemental sulfur to sulfite could be enabled by APS reductase-associated electron transfer complex QmoABC and heterodisulfide reductase. The genome also contains several membrane linked molybdopterin oxidoreductases that are thought to be involved in sulfur metabolism as subunits of thiosulfate, polysulfide, or tetrathionate reductases. Nitrate could be used as an electron acceptor and reduced to ammonium, as indicated by the presence of periplasmic nitrate and nitrite reductases. Autotrophic carbon fixation is enabled by the Wood-Ljungdahl pathway, and the complete set of genes that is required for nitrogen fixation is also present in T. dismutans. Overall, our results provide genomic insights into energy and carbon metabolism of chemolithoautotrophic sulfur-disproportionating bacterium that could be important primary producer in microbial communities of deep-sea hydrothermal vents. PMID- 27379080 TI - Corrigendum: Integrating DNA Methylation and Gene Expression Data in the Development of the Soybean-Bradyrhizobium N2-Fixing Symbiosis. AB - [This corrects the article on p. 518 in vol. 7, PMID: 27148207.]. PMID- 27379081 TI - Symbiotic Association with Mycoplasma hominis Can Influence Growth Rate, ATP Production, Cytolysis and Inflammatory Response of Trichomonas vaginalis. AB - The symbiosis between the parasitic protist Trichomonas vaginalis and the opportunistic bacterium Mycoplasma hominis is the only one currently described involving two obligate human mucosal symbionts with pathogenic capabilities that can cause independent diseases in the same anatomical site: the lower urogenital tract. Although several aspects of this intriguing microbial partnership have been investigated, many questions on the influence of this symbiosis on the parasite pathobiology still remain unanswered. Here, we examined with in vitro cultures how M. hominis could influence the pathobiology of T. vaginalis by investigating the influence of M. hominis on parasite replication rate, haemolytic activity and ATP production. By comparing isogenic mycoplasma-free T. vaginalis and parasites stably associated with M. hominis we could demonstrate that the latter show a higher replication rate, increased haemolytic activity and are able to produce larger amounts of ATP. In addition, we demonstrated in a T. vaginalis-macrophage co-culture system that M. hominis could modulate an aspect of the innate immuno-response to T. vaginalis infections by influencing the production of nitric oxide (NO) by human macrophages, with the parasite-bacteria symbiosis outcompeting the human cells for the key substrate arginine. These results support a model in which the symbiosis between T. vaginalis and M. hominis influences host-microbes interactions to the benefit of both microbial partners during infections and to the detriment of their host. PMID- 27379082 TI - IL-36gamma Augments Host Defense and Immune Responses in Human Female Reproductive Tract Epithelial Cells. AB - IL-36gamma is a proinflamatory cytokine which belongs to the IL-1 family of cytokines. It is expressed in the skin and by epithelial cells (ECs) lining lung and gut tissue. We used human 3-D organotypic cells, that recapitulate either in vivo human vaginal or cervical tissue, to explore the possible role of IL-36gamma in host defense against pathogens in the human female reproductive tract (FRT). EC were exposed to compounds derived from virus or bacterial sources and induction and regulation of IL-36gamma and its receptor was determined. Polyinosinic-polycytidylic acid (poly I:C), flagellin, and synthetic lipoprotein (FSL-1) significantly induced expression of IL-36gamma in a dose-dependent manner, and appeared to be TLR-dependent. Recombinant IL-36gamma treatment resulted in self-amplification of IL-36gamma and its receptor (IL-36R) via increased gene expression, and promoted other inflammatory signaling pathways. This is the first report to demonstrate that the IL-36 receptor and IL-36gamma are present in the human FRT EC and that they are differentially induced by microbial products at this site. We conclude that IL-36gamma is a driver for epithelial and immune activation following microbial insult and, as such, may play a critical role in host defense in the FRT. PMID- 27379083 TI - Composition of Gut Microbiota Influences Resistance of Newly Hatched Chickens to Salmonella Enteritidis Infection. AB - Since poultry is a very common source of non-typhoid Salmonella for humans, different interventions aimed at decreasing the prevalence of Salmonella in chickens are understood as an effective measure for decreasing the incidence of human salmonellosis. One such intervention is the use of probiotic or competitive exclusion products. In this study we tested whether microbiota from donor hens of different age will equally protect chickens against Salmonella Enteritidis infection. Newly hatched chickens were therefore orally inoculated with cecal extracts from 1-, 3-, 16-, 28-, and 42-week-old donors and 7 days later, the chickens were infected with S. Enteritidis. The experiment was terminated 4 days later. In the second experiment, groups of newly hatched chickens were inoculated with cecal extracts of 35-week-old hens either on day 1 of life followed by S. Enteritidis infection on day 2 or were infected with S. Enteritidis infection on day 1 followed by therapeutic administration of the cecal extract on day 2 or were inoculated on day 1 of life with a mixture of the cecal extract and S. Enteritidis. This experiment was terminated when the chickens were 5 days old. Both Salmonella culture and chicken gene expression confirmed that inoculation of newly hatched chickens with microbiota from 3-week-old or older chickens protected them against S. Enteritidis challenge. On the other hand, microbiota from 1-week-old donors failed to protect chickens against S. Enteritidis challenge. Microbiota from 35-week-old hens protected chickens even 24 h after administration. However, simultaneous or therapeutic microbiota administration failed to protect chickens against S. Enteritidis infection. Gut microbiota can be used as a preventive measure against S. Enteritidis infection but its composition and early administration is critical for its efficacy. PMID- 27379084 TI - Relationships between the Regulatory Systems of Quorum Sensing and Multidrug Resistance. AB - Cell-cell communications, known as quorum sensing (QS) in bacteria, involve the signal molecules as chemical languages and the corresponding receptors as transcriptional regulators. In Gram-negative bacteria, orphan LuxR receptors recognize signals more than just acylhomoserine lactones, and modulate interspecies and interkingdom communications. Whereas, in the Gram-positive Streptomyces, pseudo gamma-butyrolactones (GBLs) receptors bind antibiotics other than GBL signals, and coordinate antibiotics biosynthesis. By interacting with structurally diverse molecules like antibiotics, the TetR family receptors regulate multidrug resistance (MDR) by controlling efflux pumps. Antibiotics at subinhibitory concentration may act as signal molecules; while QS signals also have antimicrobial activity at high concentration. Moreover, the QS and MDR systems may share the same exporters to transport molecules. Among these orphan LuxR, pseudo GBL receptors, and MDR regulators, although only with low sequence homology, they have some structure similarity and function correlation. Therefore, perhaps there might be evolutionary relationship and biological relevance between the regulatory systems of QS and MDR. Since the QS systems become new targets for antimicrobial strategy, it would expand our understanding about the evolutionary history of these regulatory systems. PMID- 27379085 TI - Neurological Sequelae Resulting from Encephalitic Alphavirus Infection. AB - The recent surge in viral clinical cases and associated neurological deficits have reminded us that viral infections can lead to detrimental, long-term effects, termed sequelae, in survivors. Alphaviruses are enveloped, single stranded positive-sense RNA viruses in the Togaviridae family. Transmission of alphaviruses between and within species occurs mainly via the bite of an infected mosquito bite, giving alphaviruses a place among arboviruses, or arthropod-borne viruses. Alphaviruses are found throughout the world and typically cause arthralgic or encephalitic disease in infected humans. Originally detected in the 1930s, today the major encephalitic viruses include Venezuelan, Western, and Eastern equine encephalitis viruses (VEEV, WEEV, and EEEV, respectively). VEEV, WEEV, and EEEV are endemic to the Americas and are important human pathogens, leading to thousands of human infections each year. Despite awareness of these viruses for nearly 100 years, we possess little mechanistic understanding regarding the complications (sequelae) that emerge after resolution of acute infection. Neurological sequelae are those complications involving damage to the central nervous system that results in cognitive, sensory, or motor deficits that may also manifest as emotional instability and seizures in the most severe cases. This article serves to provide an overview of clinical cases documented in the past century as well as a summary of the reported neurological sequelae due to VEEV, WEEV, and EEEV infection. We conclude with a treatise on the utility of, and practical considerations for animal models applied to the problem of neurological sequelae of viral encephalopathies in order to decipher mechanisms and interventional strategies. PMID- 27379086 TI - Human Oncogenic Herpesvirus and Post-translational Modifications - Phosphorylation and SUMOylation. AB - Pathogens, especially viruses, evolve abilities to utilize cellular machineries to facilitate their survival and propagation. Post-translational modifications (PTMs), especially phosphorylation and SUMOylation, that reversibly modulate the function and interactions of target proteins are among the most important features in cell signaling pathways. PTM-dependent events also serve as one of the favorite targets for viruses. Among the seven unambiguous human oncogenic viruses, hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), human papillomavirus (HPV), Human T lymphotrophic virus-1 (HTLV-1), and Merkel cell polyomavirus (MCPyV), two are herpesviruses. The life cycle of herpesviruses consists of latent and lytic phases and the rapid switch between these states includes global remodeling of the viral genome from heterochromatin-to-euchromatin. The balance between lytic replication and latency is essential for herpesvirus to maintain a persistent infection through a combination of viral propagation and evasion of the host immune response, which consequently may contribute to tumorigenesis. It is no surprise that the swift reversibility of PTMs, especially SUMOylation, a modification that epigenetically regulates chromatin structure, is a major hijack target of the host for oncogenic herpesviruses. In this brief review, we summarize the varied ways in which herpesviruses engage the host immune components through PTMs, focusing on phosphorylation and SUMOylation. PMID- 27379087 TI - Current Technological Improvements in Enzymes toward Their Biotechnological Applications. AB - Enzymes from extremophiles are creating interest among researchers due to their unique properties and the enormous power of catalysis at extreme conditions. Since community demands are getting more intensified, therefore, researchers are applying various approaches viz. metagenomics to increase the database of extremophilic species. Furthermore, the innovations are being made in the naturally occurring enzymes utilizing various tools of recombinant DNA technology and protein engineering, which allows redesigning of the enzymes for its better fitment into the process. In this review, we discuss the biochemical constraints of psychrophiles during survival at the lower temperature. We summarize the current knowledge about the sources of such enzymes and their in vitro modification through mutagenesis to explore their biotechnological potential. Finally, we recap the microbial cell surface display to enhance the efficiency of the process in cost effective way. PMID- 27379088 TI - Modulation of Adjuvant Arthritis by Cellular and Humoral Immunity to Hsp65. AB - Heat shock proteins (Hsps) are highly conserved, and their expression is upregulated in cells by heat and other stressful stimuli. These proteins play a vital role in preserving the structural and functional integrity of cells under stress. Despite the ubiquitous expression of Hsps in an individual, the immune system is not fully tolerant to them. In fact, Hsps are highly immunogenic in nature, and immune response to these proteins is observed in various inflammatory and autoimmune diseases. Studies on the immunopathogenesis of autoimmune arthritis in the rat adjuvant arthritis (AA) model of human rheumatoid arthritis (RA) as well as observations in patients with RA and juvenile idiopathic arthritis (JIA) have unraveled immunoregulatory attributes of self-Hsp65-directed immunity. Notable features of Hsp65 immunity in AA include protection rather than disease induction following immunization of Lewis rats with self (rat)-Hsp65; the diversification of T cell response to mycobacterial Hsp65 during the course of AA and its association with spontaneous induction of response to self-Hsp65; the cross-reactive T cells recognizing foreign and self homologs of Hsp65 and their role in disease suppression in rats; the suppressive effect of antibodies to Hsp65 in AA; and the use of Hsp65, its peptides, or altered peptide ligands in controlling autoimmune pathology. The results of studies in the AA model have relevance to RA and JIA. We believe that these insights into Hsp65 immunity would not only advance our understanding of the disease process in RA/JIA, but also lead to the development of novel therapeutic approaches for autoimmune arthritis. PMID- 27379089 TI - Genetic Diagnosis Using Whole Exome Sequencing in Common Variable Immunodeficiency. AB - Whole exome sequencing (WES) has proven an effective tool for the discovery of genetic defects in patients with primary immunodeficiencies (PIDs). However, success in dissecting the genetic etiology of common variable immunodeficiency (CVID) has been limited. We outline a practical framework for using WES to identify causative genetic defects in these subjects. WES was performed on 50 subjects diagnosed with CVID who had at least one of the following criteria: early onset, autoimmune/inflammatory manifestations, low B lymphocytes, and/or familial history of hypogammaglobulinemia. Following alignment and variant calling, exomes were screened for mutations in 269 PID-causing genes. Variants were filtered based on the mode of inheritance and reported frequency in the general population. Each variant was assessed by study of familial segregation and computational predictions of deleteriousness. Out of 433 variations in PID associated genes, we identified 17 probable disease-causing mutations in 15 patients (30%). These variations were rare or private and included monoallelic mutations in NFKB1, STAT3, CTLA4, PIK3CD, and IKZF1, and biallelic mutations in LRBA and STXBP2. Forty-two other damaging variants were found but were not considered likely disease-causing based on the mode of inheritance and/or patient phenotype. WES combined with analysis of PID-associated genes is a cost-effective approach to identify disease-causing mutations in CVID patients with severe phenotypes and was successful in 30% of our cohort. As targeted therapeutics are becoming the mainstay of treatment for non-infectious manifestations in CVID, this approach will improve management of patients with more severe phenotypes. PMID- 27379090 TI - Differential Expression of Immune Checkpoint Modulators on In Vitro Primed CD4(+) and CD8(+) T Cells. AB - PD-1, TIM-3, and LAG-3 are molecules shown to have immune modulatory properties, and although initially classified as indicators of T cell hyporesponsiveness, it has become clear that they are also associated with the normal course of T cell activation. Functional studies have focused mainly on CD8(+) T cells during chronic inflammation due to interest in co-opting the cellular immune response to eliminate viral or cancerous threats; however, there remains a relative lack of data regarding the expression of these molecules on CD4(+) T cells. Here, we report that expression of the immune checkpoint (IC) molecules PD-1, LAG-3, and TIM-3 are differentially expressed on CD4(+) and CD8(+) T cells in the allogeneic response resulting from a mixed lymphocyte reaction. In these studies, PD-1 expression is higher on CD4(+) T cells compared to CD8(+) T cells. In contrast, TIM-3 is expressed at higher levels on CD8(+) T cells compared to CD4(+) T cells with an apparent reciprocity in that PD-1(+) CD4(+) T cells are frequently TIM 3(lo/-), while TIM-3-expressing CD8(+) T cells are largely PD-1(lo/-). In addition, there is a decrease in the frequency of TIM-3(+) CD4(+) cells producing IFN-gamma and IL-5 compared to TIM-3(+) CD8(+) cells. Lastly, the memory T cell phenotype within each IC-expressing subset differs between CD4(+) and CD8(+) T cells. These findings highlight key differences in IC expression patterns between CD4(+) and CD8(+) T cells and may allow for more effective therapeutic targeting of these molecules in the future. PMID- 27379091 TI - The Scavenger Receptor SREC-I Cooperates with Toll-Like Receptors to Trigger Inflammatory Innate Immune Responses. AB - Scavenger receptor expressed by endothelial cell-I (SREC-I) is a class F scavenger receptor expressed by immune cells with a significant role in CD8(+)- and CD4(+)-mediated T cell immunity. This receptor can also modulate the function of toll-like receptors (TLRs), which play essential roles in innate immunity. Earlier, it was found that human monocyte/macrophage THP1 cells and bone marrow derived macrophages from mice exhibited increased responses to polyinosine polycytidylic acid (poly I:C, PIC) and CpG (unmethylated) DNA and enhanced production of inflammatory cytokines with overexpressed SREC-I. Our data also showed that intracellular/endocytic TLR3 and TLR9 could directly interact with SREC-I in the presence of their respective ligands. We also observed that the internalized ligand along with TLR3/TLR9 colocalized in the endosome in macrophages and THP-1 cells overexpressing these receptors. In the absence of these ligands, there was no detectable colocalization between the SREC-I and endocytic TLRs. Earlier, it was shown that SREC-I stimulated double-stranded RNA/CpGDNA-mediated TLR3/TLR9 activation of the innate immune response by triggering signaling through the NF-kappaB, IRF3, and MAP kinase pathways leading to transcription of cytokine genes. We also established that SREC-I can associate with plasma membrane TLRs, such as TLR2 and TLR4. We demonstrated that SREC-I TLR4 signals more efficiently from lipid microdomain in which lipopolysaccharide (LPS) can associate with SREC-I-TLR4 complex. We also proved that SREC-I is an alternate receptor for LPS capable of internalizing the complex and for endocytic TLR ligands as well. This binding activated endocytic TLR-mediated downstream cytokine production in THP1 cells and macrophages. Finally, SREC-I could also form complexes with TLR2 and induce the release of cytokines in the presence of bacterial, viral, and fungal ligands. PMID- 27379093 TI - TIM-3 Regulates Distinct Functions in Macrophages. AB - The transmembrane protein TIM-3 is a type I protein expressed by sub-types of lymphoid cells, such as lymphocytes Th1, Th17, Tc1, NK, as well as in myeloid cells. Scientific evidence indicates that this molecule acts as a negative regulator of T lymphocyte activation and that its expression is modified in viral infections or autoimmune diseases. In addition to evidence from lymphoid cells, the function of TIM-3 has been investigated in myeloid cells, such as monocytes, macrophages, and dendritic cells (DC), where studies have demonstrated that it can regulate cytokine production, cell activation, and the capture of apoptotic bodies. Despite these advances, the function of TIM-3 in myeloid cells and the molecular mechanisms that this protein regulates are not yet fully understood. This review examines the most recent evidence concerning the function of TIM-3 when expressed in myeloid cells, primarily macrophages, and the potential impact of that function on the field of basic immunology. PMID- 27379094 TI - Complement Component C1q Programs a Pro-Efferocytic Phenotype while Limiting TNFalpha Production in Primary Mouse and Human Macrophages. AB - Deficiency in complement component C1q is associated with an inability to clear apoptotic cells (efferocytosis) and aberrant inflammation in lupus, and identification of the pathways involved in these processes should reveal important regulatory mechanisms in lupus and other autoimmune or inflammatory diseases. In this study, C1q-dependent regulation of TNFalpha/IL-6 expression and efferocytosis was investigated using primary mouse bone marrow-derived macrophages and human monocyte-derived macrophages. C1q downregulated LPS dependent TNFalpha production in mouse and human macrophages. While prolonged stimulation with C1q (18 h) was required to elicit a dampening of TNFalpha production from mouse macrophages, the human macrophages responded to C1q with immediate downregulation of TNFalpha. IL-6 production was unchanged in mouse and upregulated by human macrophages following prolonged stimulation with C1q. Our previous studies indicated that C1q programmed enhanced efferocytosis in mouse macrophages by enhancing expression of Mer tyrosine kinase and its ligand Gas6, a receptor-ligand pair that also inhibits proinflammatory signaling. Here, we demonstrated that C1q-dependent programming of human macrophage efferocytosis required protein synthesis; however, neither Mer nor the related receptor Axl was upregulated in human cells. In addition, while the C1q-collagen-like tails are sufficient for promoting C1q-dependent phagocytosis of antibody-coated targets, the C1q-tails failed to program enhanced efferocytosis or dampen TNFalpha production. These data further elucidate the mechanisms by which C1q regulates proinflammatory signaling and efferocytosis in macrophages, functions that are likely to influence the progression of autoimmunity and chronic inflammation. PMID- 27379092 TI - Mucosal Regulatory T Cells and T Helper 17 Cells in HIV-Associated Immune Activation. AB - Residual mucosal inflammation along with chronic systemic immune activation is an important feature in individuals infected with human immunodeficiency virus (HIV), and has been linked to a wide range of co-morbidities, including malignancy, opportunistic infections, immunopathology, and cardiovascular complications. Although combined antiretroviral therapy (cART) can reduce plasma viral loads to undetectable levels, reservoirs of virus persist, and increased mortality is associated with immune dysbiosis in mucosal lymphoid tissues. Immune based therapies are pursued with the goal of improving CD4(+) T-cell restoration, as well as reducing chronic immune activation in cART-treated patients. However, the majority of research on immune activation has been derived from analysis of circulating T cells. How immune cell alterations in mucosal tissues contribute to HIV immune dysregulation and the associated risk of non-infectious chronic complications is less studied. Given the significant differences between mucosal T cells and circulating T cells, and the immediate interactions of mucosal T cells with the microbiome, more attention should be devoted to mucosal immune cells and their contribution to systemic immune activation in HIV-infected individuals. Here, we will focus on mucosal immune cells with a specific emphasis on CD4(+) T lymphocytes, such as T helper 17 cells and CD4(+)Foxp3(+) regulatory T cells (Tregs), which play crucial roles in maintaining mucosal barrier integrity and preventing inflammation, respectively. We hypothesize that pro inflammatory milieu in cART-treated patients with immune activation significantly contributes to enhanced loss of Th17 cells and increased frequency of dysregulated Tregs in the mucosa, which in turn may exacerbate immune dysfunction in HIV-infected patients. We also present initial evidence to support this hypothesis. A better comprehension of how pro-inflammatory milieu impacts these two types of cells in the mucosa will shed light on mucosal immune dysfunction and HIV reservoirs, and lead to novel ways to restore immune functions in HIV(+) patients. PMID- 27379095 TI - Reconstitution of CD8 T Cells Protective against Cytomegalovirus in a Mouse Model of Hematopoietic Cell Transplantation: Dynamics and Inessentiality of Epitope Immunodominance. AB - Successful reconstitution of cytomegalovirus (CMV)-specific CD8(+) T cells by hematopoietic cell transplantation (HCT) gives a favorable prognosis for the control of CMV reactivation and prevention of CMV disease after hematoablative therapy of hematopoietic malignancies. In the transient immunocompromised state after HCT, pre-emptive cytoimmunotherapy with viral epitope-specific effector or memory CD8(+) T cells is a promising option to speed up antiviral control. Despite high-coding capacity of CMVs and a broad CD8(+) T-cell response on the population level, which reflects polymorphism in major histocompatibility complex class-I (MHC-I) glycoproteins, the response in terms of quantity of CD8(+) T cells in any individual is directed against a limited set of CMV-encoded epitopes selected for presentation by the private repertoire of MHC-I molecules. Such epitopes are known as "immunodominant" epitopes (IDEs). Besides host immunogenetics, genetic variance in CMV strains harbored as latent viruses by an individual HCT recipient can also determine the set of IDEs, which complicates a "personalized immunotherapy." It is, therefore, an important question if IDE specific CD8(+) T-cell reconstitution after HCT is critical or dispensable for antiviral control. As viruses with targeted mutations of IDEs cannot be experimentally tested in HCT patients, we employed the well-established mouse model of HCT. Notably, control of murine CMV (mCMV) after HCT was comparably efficient for IDE-deletion mutant mCMV-Delta4IDE and the corresponding IDE expressing revertant virus mCMV-Delta4IDE-rev. Thus, antigenicity-loss mutations in IDEs do not result in loss-of-function of a polyclonal CD8(+) T-cell population. Although IDE deletion was not associated with global changes in the response to non-IDE epitopes, the collective of non-IDE-specific CD8(+) T-cells infiltrates infected tissue and confines infection within nodular inflammatory foci. We conclude from the model, and predict also for human CMV, that there is no need to exclusively aim for IDE-specific immunoreconstitution. PMID- 27379096 TI - Autoimmune Myopathies: Where Do We Stand? AB - Autoimmune diseases (AIDs) as a whole represent a major health concern and remain a medical and scientific challenge. Some of them, such as multiple sclerosis or type 1 diabetes, have been actively investigated for many decades. Autoimmune myopathies (AIMs), also referred to as idiopathic inflammatory myopathies or myositis, represent a group of very severe AID for which we have a more limited pathophysiological knowledge. AIM encompass a group of, individually rare but collectively not so uncommon, diseases characterized by symmetrical proximal muscle weakness, increased serum muscle enzymes such as creatine kinase, myopathic changes on electromyography, and several typical histological patterns on muscle biopsy, including the presence of inflammatory cell infiltrates in muscle tissue. Importantly, some AIMs are strongly related to cancer. Here, we review the current knowledge on the most prevalent forms of AIM and, notably, the diagnostic contribution of autoantibodies. PMID- 27379097 TI - "Natural Regulators": NK Cells as Modulators of T Cell Immunity. AB - Natural killer (NK) cells are known as frontline responders capable of rapidly mediating a response upon encountering transformed or infected cells. Recent findings indicate that NK cells, in addition to acting as innate effectors, can also regulate adaptive immune responses. Here, we review recent studies on the immunoregulatory function of NK cells with a specific focus on their ability to affect the generation of early, as well as long-term antiviral T cell responses, and their role in modulating immune pathology and disease. In addition, we summarize the current knowledge of the factors governing regulatory NK cell responses and discuss origin, tissue specificity, and open questions about the classification of regulatory NK cells as classical NK cells versus group 1 innate lymphoid cells. PMID- 27379098 TI - Aerobic Exercise Reduces Asthma Phenotype by Modulation of the Leukotriene Pathway. AB - INTRODUCTION: Leukotrienes (LTs) play a central role in asthma. Low- to moderate intensity aerobic exercise (AE) reduces asthmatic inflammation in clinical studies and in experimental models. This study investigated whether AE attenuates LT pathway activation in an ovalbumin (OVA) model of asthma. METHODS: Sixty-four male, BALB/c mice were distributed into Control, Exercise (Exe), OVA, and OVA + Exe groups. Treadmill training was performed at moderate intensity, 5*/week, 1 h/session for 4 weeks. Quantification of bronchoalveolar lavage (BAL) cellularity, leukocytes, airway remodeling, interleukin (IL)-5, IL-13, cysteinyl leukotriene (CysLT), and leukotriene B4 (LTB4) in BAL was performed. In addition, quantitative analyses on peribronchial leukocytes and airway epithelium for LT pathway agents: 5-lypoxygenase (5-LO), LTA4 hydrolase (LTA4H), CysLT1 receptor, CysLT2 receptor, LTC4 synthase, and LTB4 receptor 2 (BLT2) were performed. Airway hyperresponsiveness (AHR) to methacholine (MCh) was assessed via whole body plethysmography. RESULTS: AE decreased eosinophils (p < 0.001), neutrophils (p > 0.001), lymphocytes (p < 0.001), and macrophages (p < 0.01) in BAL, as well as eosinophils (p < 0.01), lymphocytes (p < 0.001), and macrophages (p > 0.001) in airway walls. Collagen (p < 0.01), elastic fibers (p < 0.01), mucus production (p < 0.01), and smooth muscle thickness (p < 0.01), as well as IL-5 (p < 0.01), IL 13 (p < 0.01), CysLT (p < 0.01), and LTB4 (p < 0.01) in BAL were reduced. 5-LO (p < 0.05), LTA4H (p < 0.05), CysLT1 receptor (p < 0.001), CysLT2 receptor (p < 0.001), LTC4 synthase (p < 0.001), and BLT2 (p < 0.01) expression by peribronchial leukocytes and airway epithelium were reduced. Lastly, AHR to MCh 25 mg/mL (p < 0.05) and 50 mg/mL (p < 0.01) was reduced. CONCLUSION: Moderate intensity AE attenuated asthma phenotype and LT production in both pulmonary leukocytes and airway epithelium of OVA-treated mice. PMID- 27379099 TI - Pharmacologic Inhibition of Host Phosphodiesterase-4 Improves Isoniazid-Mediated Clearance of Mycobacterium tuberculosis. AB - The lengthy duration of multidrug therapy needed to cure tuberculosis (TB) poses significant challenges for global control of the disease. Moreover, chronic inflammation associated with TB leads to pulmonary damage that can remain even after successful cure. Thus, there is a great need for the development of effective shorter drug regimens to improve clinical outcome and strengthen TB control. Host-directed therapy (HDT) is emerging as a novel adjunctive strategy to enhance the efficacy and shorten the duration of TB treatment. Previously, we showed that the administration of CC-3052, a phosphodiesterase-4 inhibitor (PDE4i), reduced the host inflammatory response during Mycobacterium tuberculosis (Mtb) infection and improved the antimicrobial efficacy of isoniazid (INH) in both the mouse and rabbit models. In the present study, we evaluated the pharmacokinetics and explored the mechanism underlying the efficacy of a more potent PDE4i, CC-11050, as adjunct to INH treatment in a mouse model of pulmonary Mtb infection. Genome-wide lung transcriptome analysis confirmed the dampening of inflammation and associated network genes that we previously reported with CC 3052. Consistent with the reduction in inflammation, a significant improvement in Mtb control and pathology was observed in the lungs of mice treated with CC-11050 plus INH, compared to INH alone. This important confirmatory study will be used to help design upcoming human clinical trials with CC-11050 as an HDT for TB treatment. PMID- 27379100 TI - Combined Expression of IFN-gamma, IL-17, and IL-4 mRNA by Recall PBMCs Moderately Discriminates Active Tuberculosis from Latent Mycobacterium tuberculosis Infection in Patients with Miscellaneous Inflammatory Underlying Conditions. AB - New biomarkers are needed for discriminating active tuberculosis (TB) from latent TB infection (LTBI), especially in vulnerable groups representing the major diagnostic challenge. This pilot study was carried out to explore the diagnostic potential of selected genes, IFN-gamma, IL-17, IL-4, and FoxP3, associated with TB immunity and immunopathology. IFN-gamma, IL-17, IL-4, and FoxP3 mRNA expression levels were measured by quantitative reverse transcription PCR (RT qPCR) from antigen-stimulated peripheral blood mononuclear cells of patients with active TB (n = 25); patients with miscellaneous inflammatory disorders and concomitant LTBI (n = 20), rheumatoid arthritis (RA) being the most predominant in the group (n = 11); and in healthy Bacillus Calmette-Guerin (BCG) vaccinees (n = 8). While the levels of FoxP3 mRNA did not differ between the tested groups, the cumulative expression levels of purified protein derivative-stimulated IFN gamma, IL-17, and IL-4 mRNAs were found to distinguish active TB from the whole group of LTBI with 48% sensitivity and 85% specificity. When restricting the LTBI group to RA cases only, the sensitivity was 56% and specificity 100%. When interpreting the result as positive in at least one of the mRNAs IFN-gamma, IL 17, or IL-4, sensitivity of 64% and specificities of 75% (heterogeneous group of LTBI) or 100% (LTBI with RA) were achieved. Moderate discrimination of active TB from LTBI with miscellaneous inflammatory underlying conditions by using combined quantitative expression of IFN-gamma, IL-17, and IL-4 mRNA seems not to be of high diagnostic potential. PMID- 27379101 TI - T-bet and Eomesodermin in NK Cell Development, Maturation, and Function. AB - Recent reports give insights into the role of the T-box transcription factors, T bet and Eomesodermin (Eomes), in NK cell biology. In this mini-review, we recapitulate the initial reports that delineate T-bet and Eomes as master regulators of NK cell development, maturation, and function. We discuss how T-bet and Eomes expression is regulated during NK cell development and peripheral maturation. Furthermore, we summarize the current literature on the role of T-bet and Eomes in the transcriptional regulation of NK cell function and review possible effects of T-box transcription factor anomalies during aging, infection, cancer, and after hematopoietic stem cell transplantation. We discuss how the current data argue in favor of a model of T-bet and Eomes synergy in transcriptional regulation of NK cell function and identify T-box transcription factors as potential targets for therapeutic interventions. PMID- 27379102 TI - Unveiling the Redox Control of Plant Reproductive Development during Abiotic Stress. AB - Plants being sessile in nature are often challenged to various abiotic stresses including temperature fluctuations, water supply, salinity, and nutrient availability. Exposure of plants to such environmental perturbations result in the formation of reactive oxygen species (ROS) in cells. To scavenge ROS, enzymatic and molecular antioxidants are produced at a cellular level. ROS act as a signaling entity at lower concentrations maintaining normal growth and development, but if their levels increase beyond certain threshold, they produce toxic effects in plants. Some developmental stages, such as development of reproductive organs are more sensitive to abiotic stress than other stages of growth. As success of plant reproductive development is directly correlated with grain yield, stresses coinciding with reproductive phase results in the higher yield losses. In this article, we summarize the redox control of plant reproductive development, and elaborate how redox homeostasis is compromised during abiotic stress exposure. We highlight why more emphasis should be given to understand redox control of plant reproductive organ development during abiotic stress exposure96to engineer crops with better crop yield. We specifically discuss the role of ROS as a signaling molecule and its cross-talk with other signaling molecules such as hormones and sugars. PMID- 27379103 TI - Transient Expression of Tetrameric Recombinant Human Butyrylcholinesterase in Nicotiana benthamiana. AB - To optimize the expression, extraction and purification of plant-derived tetrameric recombinant human butyrylcholinesterase (prBChE), we describe the development and use of plant viral amplicon-based gene expression system; Tobacco Mosaic Virus (TMV) RNA-based overexpression vector (TRBO) to express enzymatically active FLAG-tagged plant made recombinant butyrylcholinesterase (rBChE) in Nicotiana benthamiana leaves using transient agroinfiltration. Two gene expression cassettes were designed to express the recombinant protein in either the ER or to the apoplastic compartment. Leaf homogenization was used to isolate ER-retained recombinant butyrylcholinesterase (prBChE-ER) while apoplast targeted rBChE was isolated by either leaf homogenization (prBChE) or vacuum extraction of apoplastic wash fluid (prBChE-AWF). rBChE from apoplast wash fluid had a higher specific activity but lower enzyme yield than leaf homogenate. To optimize the isolation and purification of total recombinant protein from leaf homogenates, an acidic extraction buffer was used. The acidic extraction buffer yielded >95% enzymatically active tetrameric rBChE as verified by Coomassie stained and native gel electrophoresis. Furthermore, when compared to human butyrylcholinesterase, the prBChE was found to be similar in terms of tetramerization and enzyme kinetics. The N-linked glycan profile of purified prBChE-ER was found to be mostly high mannose structures while the N-linked glycans on prBChE-AWF were primarily complex. The glycan profile of the prBChE leaf homogenates showed a mixture of high mannose, complex and paucimannose type N-glycans. These findings demonstrate the ability of plants to produce rBChE that is enzymatically active and whose oligomeric state is comparable to mammalian butyrylcholinesterase. The process of plant made rBChE tetramerization and strategies for improving its pharmacokinetics properties are also discussed. PMID- 27379104 TI - Silicon: Potential to Promote Direct and Indirect Effects on Plant Defense Against Arthropod Pests in Agriculture. AB - Silicon has generally not been considered essential for plant growth, although it is well recognized that many plants, particularly Poaceae, have substantial plant tissue concentrations of this element. Recently, however, the International Plant Nutrition Institute [IPNI] (2015), Georgia, USA has listed it as a "beneficial substance". This reflects that numerous studies have now established that silicon may alleviate both biotic and abiotic stress. This paper explores the existing knowledge and recent advances in elucidating the role of silicon in plant defense against biotic stress, particularly against arthropod pests in agriculture and attraction of beneficial insects. Silicon confers resistance to herbivores via two described mechanisms: physical and biochemical/molecular. Until recently, studies have mainly centered on two trophic levels; the herbivore and plant. However, several studies now describe tri-trophic effects involving silicon that operate by attracting predators or parasitoids to plants under herbivore attack. Indeed, it has been demonstrated that silicon-treated, arthropod-attacked plants display increased attractiveness to natural enemies, an effect that was reflected in elevated biological control in the field. The reported relationships between soluble silicon and the jasmonic acid (JA) defense pathway, and JA and herbivore induced plant volatiles (HIPVs) suggest that soluble silicon may enhance the production of HIPVs. Further, it is feasible that silicon uptake may affect protein expression (or modify proteins structurally) so that they can produce additional, or modify, the HIPV profile of plants. Ultimately, understanding silicon under plant ecological, physiological, biochemical, and molecular contexts will assist in fully elucidating the mechanisms behind silicon and plant response to biotic stress at both the bi- and tri-trophic levels. PMID- 27379106 TI - Copper-Induced Membrane Depolarizations Involve the Induction of Mosaic TRP Channels, Which Activate VDCC Leading to Calcium Increases in Ulva compressa. AB - The marine macroalga Ulva compressa (Chlorophyceae) is a cosmopolitan species, tolerant to heavy metals, in particular to copper. U. compressa was cultivated with 10 MUM copper for 12 h and membrane depolarization events were detected. First, seven depolarization events occurred at 4, 8, 12-13, 80, and 86 min, and at 5 and 9 h of copper exposure. Second, bathocuproine sulphonate, a specific copper-chelating compound, was added before incorporating copper to the culture medium. Copper-induced depolarizations were inhibited by bathocuproine at 4, 8, 12-13, 80, and 86 min, but not at 5 and 9 h, indicating that initial events are due to copper ions entry. Third, specific inhibitors of human TRPA1, C4, C5, M8, and V1corresponding to HC030031, ML204, SKF96363, M8B, and capsazepin, respectively, were used to analyze whether copper-induced depolarizations were due to activation of transient receptor potentials (TRPs). Inhibitor effects indicate that the seven depolarizations involved the activation of functional mosaic TRPs that displayed properties similar to human TRPA, C, M, and/or V. Finally, inhibition of copper-induced depolarizations using specific TRP inhibitors suppressed calcium increases at 2, 3, and 12 h due to activation of voltage-dependent calcium channels (VDCCs). Thus, copper induces seven depolarization events that involve activation of mosaic TRPs which, in turn, activates VDCC leading to calcium increases at 2, 3, and 12 h in U. compressa. PMID- 27379105 TI - Desiccation and Mortality Dynamics in Seedlings of Different European Beech (Fagus sylvatica L.) Populations under Extreme Drought Conditions. AB - European beech (Fagus sylvatica L., hereafter beech), one of the major native tree species in Europe, is known to be drought sensitive. Thus, the identification of critical thresholds of drought impact intensity and duration are of high interest for assessing the adaptive potential of European beech to climate change in its native range. In a common garden experiment with one-year old seedlings originating from central and marginal origins in six European countries (Denmark, Germany, France, Romania, Bosnia-Herzegovina, and Spain), we applied extreme drought stress and observed desiccation and mortality processes among the different populations and related them to plant water status (predawn water potential, PsiPD) and soil hydraulic traits. For the lethal drought assessment, we used a critical threshold of soil water availability that is reached when 50% mortality in seedling populations occurs (LD50SWA). We found significant population differences in LD50SWA (10.5-17.8%), and mortality dynamics that suggest a genetic difference in drought resistance between populations. The LD50SWA values correlate significantly with the mean growing season precipitation at population origins, but not with the geographic margins of beech range. Thus, beech range marginality may be more due to climatic conditions than to geographic range. The outcome of this study suggests the genetic variation has a major influence on the varying adaptive potential of the investigated populations. PMID- 27379107 TI - Over-Expression of the Pikh Gene with a CaMV 35S Promoter Leads to Improved Blast Disease (Magnaporthe oryzae) Tolerance in Rice. AB - Magnaporthe oryzae is a rice blast fungus and plant pathogen that causes a serious rice disease and, therefore, poses a threat to the world's second most important food security crop. Plant transformation technology has become an adaptable system for cultivar improvement and to functionally analyze genes in plants. The objective of this study was to determine the effects (through over expressing and using the CaMV 35S promoter) of Pikh on MR219 resistance because it is a rice variety that is susceptible to the blast fungus pathotype P7.2. Thus, a full DNA and coding DNA sequence (CDS) of the Pikh gene, 3172 bp, and 1206 bp in length, were obtained through amplifying the gDNA and cDNA template from a PH9-resistant rice variety using a specific primer. Agrobacterium-mediated transformation technology was also used to introduce the Pikh gene into the MR219 callus. Subsequently, transgenic plants were evaluated from the DNA to protein stages using polymerase chain reaction (PCR), semi-quantitative RT-PCR, real-time quantitative PCR and high performance liquid chromatography (HPLC). Transgenic plants were also compared with a control using a real-time quantification technique (to quantify the pathogen population), and transgenic and control plants were challenged with the local most virulent M. oryzae pathotype, P7.2. Based on the results, the Pikh gene encodes a hydrophilic protein with 18 sheets, 4 helixes, and 21 coils. This protein contains 401 amino acids, among which the amino acid sequence from 1 to 376 is a non-cytoplasmic region, that from 377 to 397 is a transmembrane region, and that from 398 to 401 is a cytoplasmic region with no identified disordered regions. The Pikh gene was up-regulated in the transgenic plants compared with the control plants. The quantity of the amino acid leucine in the transgenic rice plants increased significantly from 17.131 in the wild-type to 47.865 mg g(-1) in transgenic plants. The M. oryzae population was constant at 31, 48, and 72 h after inoculation in transgenic plants, while it was increased in the inoculated control plants. This study successfully clarified that over-expression of the Pikh gene in transgenic plants can improve their blast resistance against the M. oryzae pathotype P7.2. PMID- 27379108 TI - Flood-Ring Formation and Root Development in Response to Experimental Flooding of Young Quercus robur Trees. AB - Spring flooding in riparian forests can cause significant reductions in earlywood vessel size in submerged stem parts of ring-porous tree species, leading to the presence of 'flood rings' that can be used as a proxy to reconstruct past flooding events, potentially over millennia. The mechanism of flood-ring formation and the relation with timing and duration of flooding are still to be elucidated. In this study, we experimentally flooded 4-year-old Quercus robur trees at three spring phenophases (late bud dormancy, budswell, and internode expansion) and over different flooding durations (2, 4, and 6 weeks) to a stem height of 50 cm. The effect of flooding on root and vessel development was assessed immediately after the flooding treatment and at the end of the growing season. Ring width and earlywood-vessel size and density were measured at 25- and 75-cm stem height and collapsed vessels were recorded. Stem flooding inhibited earlywood-vessel development in flooded stem parts. In addition, flooding upon budswell and internode expansion led to collapsed earlywood vessels below the water level. At the end of the growing season, mean earlywood-vessel size in the flooded stem parts (upon budswell and internode expansion) was always reduced by approximately 50% compared to non-flooded stem parts and 55% compared to control trees. This reduction was already present 2 weeks after flooding and occurred independent of flooding duration. Stem and root flooding were associated with significant root dieback after 4 and 6 weeks and mean radial growth was always reduced with increasing flooding duration. By comparing stem and root flooding, we conclude that flood rings only occur after stem flooding. As earlywood-vessel development was hampered during flooding, a considerable number of narrow earlywood vessels present later in the season, must have been formed after the actual flooding events. Our study indicates that root dieback, together with strongly reduced hydraulic conductivity due to anomalously narrow earlywood vessels in flooded stem parts, contribute to reduced radial growth after flooding events. Our findings support the value of flood rings to reconstruct spring flooding events that occurred prior to instrumental flood records. PMID- 27379109 TI - Genotyping-by-Sequencing SNP Identification for Crops without a Reference Genome: Using Transcriptome Based Mapping as an Alternative Strategy. AB - Next-generation sequencing opens the way for genomic studies of diversity even for non-model crops and animals. Genome reduction techniques are becoming progressively more popular as they allow a fraction of the genome to be sequenced for multiple individuals and/or populations. These techniques are an efficient way to explore genome diversity in non-model crops and animals for which no reference genome is available. Genome reduction techniques emerged with the development of specific pipelines such as UNEAK (Universal Network Enabled Analysis Kit) and Stacks. However, even for non-model crops and animals, transcriptomes are easier to obtain, thereby making it possible to directly map reads. We investigate the direct use of transcriptome as an alternative strategy. Our specific objective was to compare SNPs obtained from the UNEAK pipeline as well as SNPs obtained by directly mapping genotyping-by-sequencing reads on a transcriptome. We assessed the feasibility of both SNP datasets, UNEAK and transcriptome mapping, to investigate the diversity of 91 samples of wild pearl millet sampled across its distribution area. Both approaches produced several tens of thousands of single nucleotide variants, but differed in the way the variants were identified, leading to differences in the frequency spectrum associated with marked differences in the assessment of diversity. Difference in the frequency spectrum significantly biased a large set of diversity analyses as well as detection of selection approaches. However, whatever the approach, we found very similar inference of genetic structure, with three major genetic groups from West, Central, and East Africa. For non-model crops, using transcriptome data as a reference is thus a particularly promising way to obtain a more thorough analysis of datasets generated using genome reduction techniques. PMID- 27379110 TI - Transcriptome- Assisted Label-Free Quantitative Proteomics Analysis Reveals Novel Insights into Piper nigrum-Phytophthora capsici Phytopathosystem. AB - Black pepper (Piper nigrum L.), a tropical spice crop of global acclaim, is susceptible to Phytophthora capsici, an oomycete pathogen which causes the highly destructive foot rot disease. A systematic understanding of this phytopathosystem has not been possible owing to lack of genome or proteome information. In this study, we explain an integrated transcriptome-assisted label-free quantitative proteomics pipeline to study the basal immune components of black pepper when challenged with P. capsici. We report a global identification of 532 novel leaf proteins from black pepper, of which 518 proteins were functionally annotated using BLAST2GO tool. A label-free quantitation of the protein datasets revealed 194 proteins common to diseased and control protein datasets of which 22 proteins showed significant up-regulation and 134 showed significant down-regulation. Ninety-three proteins were identified exclusively on P. capsici infected leaf tissues and 245 were expressed only in mock (control) infected samples. In-depth analysis of our data gives novel insights into the regulatory pathways of black pepper which are compromised during the infection. Differential down-regulation was observed in a number of critical pathways like carbon fixation in photosynthetic organism, cyano-amino acid metabolism, fructose, and mannose metabolism, glutathione metabolism, and phenylpropanoid biosynthesis. The proteomics results were validated with real-time qRT-PCR analysis. We were also able to identify the complete coding sequences for all the proteins of which few selected genes were cloned and sequence characterized for further confirmation. Our study is the first report of a quantitative proteomics dataset in black pepper which provides convincing evidence on the effectiveness of a transcriptome based label-free proteomics approach for elucidating the host response to biotic stress in a non-model spice crop like P. nigrum, for which genome information is unavailable. Our dataset will serve as a useful resource for future studies in this plant. Data are available via ProteomeXchange with identifier PXD003887. PMID- 27379111 TI - FcLDP1, a Gene Encoding a Late Embryogenesis Abundant (LEA) Domain Protein, Responds to Brassinosteroids and Abscisic Acid during the Development of Fruits in Fragaria chiloensis. AB - White Chilean strawberries (Fragaria chiloensis) are non-climacteric fruits, with an exotic color and aroma. In order to discover genes involved in the development of these fruits, we identified a fragment of a gene encoding a late embryogenesis abundant domain protein, FcLDP1, that was expressed in early stages of fruit development, particularly in receptacles. Hormones play key roles in regulating the development of non-climacteric fruits. We show that the brassinosteroid content of the white strawberry varies during development. Additionally, FcLDP1 as well as the closest ortholog in the woodland strawberry, F. vesca (FvLDP1) possess multiple brassinosteroid, as well as abscisic acid (ABA) response motifs in the promoter region, consistent with the response of transiently expressed FcLDP1 promoter-GFP fusions to these hormones, and the rise in FcLDP1 transcript levels in white strawberry fruits treated with brassinosteroids or ABA. These findings suggest that both hormones regulate FcLDP1 expression during the development of white strawberries. PMID- 27379112 TI - Intraspecific Variation in Wood Anatomical, Hydraulic, and Foliar Traits in Ten European Beech Provenances Differing in Growth Yield. AB - In angiosperms, many studies have described the inter-specific variability of hydraulic-related traits and little is known at the intra-specific level. This information is however mandatory to assess the adaptive capacities of tree populations in the context of increasing drought frequency and severity. Ten 20 year old European beech (Fagus sylvatica L.) provenances representing the entire distribution range throughout Europe and differing significantly in aboveground biomass increment (ABI) by a factor of up to four were investigated for branch wood anatomical, hydraulic, and foliar traits in a provenance trial located in Northern Europe. We quantified to which extend xylem hydraulic and leaf traits are under genetic control and tested whether the xylem hydraulic properties (hydraulic efficiency and safety) trades off with yield and wood anatomical and leaf traits. Our results showed that only three out of 22 investigated ecophysiological traits showed significant genetic differentiations between provenances, namely vessel density (VD), the xylem pressure causing 88% loss of hydraulic conductance and mean leaf size. Depending of the ecophysiological traits measured, genetic differentiation between populations explained 0-14% of total phenotypic variation, while intra-population variability was higher than inter-population variability. Most wood anatomical traits and some foliar traits were additionally related to the climate of provenance origin. The lumen to sapwood area ratio, vessel diameter, theoretical specific conductivity and theoretical leaf-specific conductivity as well as the C:N-ratio increased with climatic aridity at the place of origin while the carbon isotope signature (delta(13)C) decreased. Contrary to our assumption, none of the wood anatomical traits were related to embolism resistance but were strong determinants of hydraulic efficiency. Although ABI was associated with both VD and delta(13)C, both hydraulic efficiency and embolism resistance were unrelated, disproving the assumed trade-off between hydraulic efficiency and safety. European beech seems to compensate increasing water stress with growing size mainly by adjusting vessel number and not vessel diameter. In conclusion, European beech has a high potential capacity to cope with climate change due to the high degree of intra population genetic variability. PMID- 27379114 TI - Elevated CO2 Atmosphere Minimizes the Effect of Drought on the Cerrado Species Chrysolaena obovata. AB - Chrysolaena obovata stores inulin in the rhizophores, associated with drought tolerance. While crop plants are widely studied concerning the interactive effects of high [CO2] and drought, few studies reported these effects in native species. Here, we evaluated the combined effects of these factors on water status and fructan metabolism in C. obovata, a native Cerrado species. Two lots of plants were kept at 380 and 760 ppm CO2 in open-top chambers. In each, [CO2] plants were divided into four groups and cultivated under different water availability: irrigation with 100 (control), 75 (low), 50 (medium), and 25% (severe drought) of the water evapotranspirated in the last 48 h. In each, water treatment plants were collected at 0, 9, 18, and 27 days. On day 27, all plants were re-watered to field capacity and, after 5 days, a new sampling was made. Water restriction caused a decrease in plant moisture, photosynthesis, and in enzymes of fructan metabolism. These changes were generally more pronounced in 25% plants under ambient [CO2]. In the later, increases in the proportion of hexoses and consequent modification of the fructan chain sizes were more marked than under high [CO2]. The results indicate that under elevated [CO2], the negative effects of water restriction on physiological processes were minimized, including the maintenance of rhizophore water potential, increase in water use efficiency, maintenance of photosynthesis and fructan reserves for a longer period, conditions that shall favor the conservation of this species in the predicted climate change scenarios. PMID- 27379113 TI - DNA Methylation and Chromatin Regulation during Fleshy Fruit Development and Ripening. AB - Fruit ripening is a developmental process that results in the leaf-like carpel organ of the flower becoming a mature ovary primed for dispersal of the seeds. Ripening in fleshy fruits involves a profound metabolic phase change that is under strict hormonal and genetic control. This work reviews recent developments in our understanding of the epigenetic regulation of fruit ripening. We start by describing the current state of the art about processes involved in histone post translational modifications and the remodeling of chromatin structure and their impact on fruit development and ripening. However, the focus of the review is the consequences of changes in DNA methylation levels on the expression of ripening related genes. This includes those changes that result in heritable phenotypic variation in the absence of DNA sequence alterations, and the mechanisms for their initiation and maintenance. The majority of the studies described in the literature involve work on tomato, but evidence is emerging that ripening in other fruit species may also be under epigenetic control. We discuss how epigenetic differences may provide new targets for breeding and crop improvement. PMID- 27379116 TI - Extensin and Arabinogalactan-Protein Biosynthesis: Glycosyltransferases, Research Challenges, and Biosensors. AB - Recent research, mostly in Arabidopsis thaliana, has led to the identification and characterization of the glycosyltransferases responsible for the biosynthesis of two of the most functionally important and abundant families of plant cell wall proteins, extensins, and arabinogalactan-proteins. Extensin glycosylation involves monogalactosylation of serine residues by O-alpha-serine galactosyltransferase and the addition of oligoarabinosides one to five arabinose units in length to contiguous hydroxyproline residues by a set of specific arabinosyltransferase enzymes, which includes hydroxyproline O-beta arabinosyltransferases, beta-1,2-arabinosyltransferases, and at least one alpha 1,3-arabinosyltransferase. AGP glycosylation, however, is much more complex and involves the addition of large arabinogalactan polysaccharide chains to non contiguous hydroxyproline residues. These arabinogalactan chains are composed of beta-1,3-galactan backbones decorated with beta-1,6-galactose side chains that are further modified with alpha-arabinose as well as other sugars, including beta (methyl)glucuronic acid, alpha-rhamnose, and alpha-fucose. Specific sets of hydroxyproline O-beta-galactosyltransferases, beta-1,3-galactosyltransferases, beta-1,6-galactosyltransferases, alpha-arabinosyltransferases, beta glucuronosyltransferases, alpha-rhamnosyltransferases, and alpha fucosyltransferases are responsible for the synthesis of these complex structures. This mini-review summarizes the EXT and AGP glycosyltransferases identified and characterized to date along with corresponding genetic mutant data, which addresses the functional importance of EXT and AGP glycosylation. In one case, genetic mutant data indicate that the carbohydrate moiety of arabinogalactan-proteins may serve as an extracellular biosensor or signal for normal cellular growth. Finally, future research challenges with respect to understanding the function of these enzymes more completely and discovering and characterizing additional glycosyltransferases responsible for extensin and arabinogalactan-protein biosynthesis are also discussed. PMID- 27379115 TI - Jasmonates: Multifunctional Roles in Stress Tolerance. AB - Jasmonates (JAs) [Jasmonic acid (JA) and methyl jasmonates (MeJAs)] are known to take part in various physiological processes. Exogenous application of JAs so far tested on different plants under abiotic stresses particularly salinity, drought, and temperature (low/high) conditions have proved effective in improving plant stress tolerance. However, its extent of effectiveness entirely depends on the type of plant species tested or its concentration. The effects of introgression or silencing of different JA- and Me-JA-related genes have been summarized in this review, which have shown a substantial role in improving crop yield and quality in different plants under stress or non-stress conditions. Regulation of JAs synthesis is impaired in stressed as well as unstressed plant cells/tissues, which is believed to be associated with a variety of metabolic events including signal transduction. Although, mitogen activated protein kinases (MAPKs) are important components of JA signaling and biosynthesis pathways, nitric oxide, ROS, calcium, ABA, ethylene, and salicylic acid are also important mediators of plant growth and development during JA signal transduction and synthesis. The exploration of other signaling molecules can be beneficial to examine the details of underlying molecular mechanisms of JA signal transduction. Much work is to be done in near future to find the proper answers of the questions like action of JA related metabolites, and identification of universal JA receptors etc. Complete signaling pathways involving MAPKs, CDPK, TGA, SIPK, WIPK, and WRKY transcription factors are yet to be investigated to understand the complete mechanism of action of JAs. PMID- 27379118 TI - Quantification of Carbohydrates in Grape Tissues Using Capillary Zone Electrophoresis. AB - Soluble sugars play an important role in freezing tolerance in both herbaceous and woody plants, functioning in both the reduction of freezing-induced dehydration and the cryoprotection of cellular constituents. The quantification of soluble sugars in plant tissues is, therefore, essential in understanding freezing tolerance. While a number of analytical techniques and methods have been used to quantify sugars, most of these are expensive and time-consuming due to complex sample preparation procedures which require the derivatization of the carbohydrates being analyzed. Analysis of soluble sugars using capillary zone electrophoresis (CZE) under alkaline conditions with direct UV detection has previously been used to quantify simple sugars in fruit juices. However, it was unclear whether CZE-based methods could be successfully used to quantify the broader range of sugars present in complex plant extracts. Here, we present the development of an optimized CZE method capable of separating and quantifying mono , di-, and tri-saccharides isolated from plant tissues. This optimized CZE method employs a column electrolyte buffer containing 130 mM NaOH, pH 13.0, creating a current of 185 MUA when a separation voltage of 10 kV is employed. The optimized CZE method provides limits-of-detection (an average of 1.5 ng/MUL) for individual carbohydrates comparable or superior to those obtained using gas chromatography mass spectrometry, and allows resolution of non-structural sugars and cell wall components (structural sugars). The optimized CZE method was successfully used to quantify sugars from grape leaves and buds, and is a robust tool for the quantification of plant sugars found in vegetative and woody tissues. The increased analytical efficiency of this CZE method makes it ideal for use in high throughput metabolomics studies designed to quantify plant sugars. PMID- 27379117 TI - MicroRNAs As Potential Targets for Abiotic Stress Tolerance in Plants. AB - The microRNAs (miRNAs) are small (20-24 nt) sized, non-coding, single stranded riboregulator RNAs abundant in higher organisms. Recent findings have established that plants assign miRNAs as critical post-transcriptional regulators of gene expression in sequence-specific manner to respond to numerous abiotic stresses they face during their growth cycle. These small RNAs regulate gene expression via translational inhibition. Usually, stress induced miRNAs downregulate their target mRNAs, whereas, their downregulation leads to accumulation and function of positive regulators. In the past decade, investigations were mainly aimed to identify plant miRNAs, responsive to individual or multiple environmental factors, profiling their expression patterns and recognizing their roles in stress responses and tolerance. Altered expressions of miRNAs implicated in plant growth and development have been reported in several plant species subjected to abiotic stress conditions such as drought, salinity, extreme temperatures, nutrient deprivation, and heavy metals. These findings indicate that miRNAs may hold the key as potential targets for genetic manipulations to engineer abiotic stress tolerance in crop plants. This review is aimed to provide recent updates on plant miRNAs, their biogenesis and functions, target prediction and identification, computational tools and databases available for plant miRNAs, and their roles in abiotic stress-responses and adaptive mechanisms in major crop plants. Besides, the recent case studies for overexpressing the selected miRNAs for miRNA-mediated enhanced abiotic stress tolerance of transgenic plants have been discussed. PMID- 27379119 TI - Obligate Biotroph Pathogens of the Genus Albugo Are Better Adapted to Active Host Defense Compared to Niche Competitors. AB - Recent research suggested that plants behave differently under combined versus single abiotic and biotic stress conditions in controlled environments. While this work has provided a glimpse into how plants might behave under complex natural conditions, it also highlights the need for field experiments using established model systems. In nature, diverse microbes colonize the phyllosphere of Arabidopsis thaliana, including the obligate biotroph oomycete genus Albugo, causal agent of the common disease white rust. Biotrophic, as well as hemibiotrophic plant pathogens are characterized by efficient suppression of host defense responses. Lab experiments have even shown that Albugo sp. can suppress non-host resistance, thereby enabling otherwise avirulent pathogen growth. We asked how a pathogen that is vitally dependent on a living host can compete in nature for limited niche space while paradoxically enabling colonization of its host plant for competitors? To address this question, we used a proteomics approach to identify differences and similarities between lab and field samples of Albugo sp.-infected and -uninfected A. thaliana plants. We could identify highly similar apoplastic proteomic profiles in both infected and uninfected plants. In wild plants, however, a broad range of defense-related proteins were detected in the apoplast regardless of infection status, while no or low levels of defense-related proteins were detected in lab samples. These results indicate that Albugo sp. do not strongly affect immune responses and leave distinct branches of the immune signaling network intact. To validate our findings and to get mechanistic insights, we tested a panel of A. thaliana mutant plants with induced or compromised immunity for susceptibility to different biotrophic pathogens. Our findings suggest that the biotroph pathogen Albugo selectively interferes with host defense under different environmental and competitive pressures to maintain its ecological niche dominance. Adaptation to host immune responses while maintaining a partially active host immunity seems advantageous against competitors. We suggest a model for future research that considers not only host-microbe but in addition microbe-microbe and microbe-host environment factors. PMID- 27379120 TI - Polyploidy can Confer Superiority to West African Acacia senegal (L.) Willd. Trees. AB - Polyploidy is a common phenomenon in the evolution of angiosperms. It has been suggested that polyploids manage harsh environments better than their diploid relatives but empirical data supporting this hypothesis are scarce, especially for trees. Using microsatellite markers and flow cytometry, we examine the frequency of polyploids and diploids in a progeny trial testing four different populations of Acacia senegal, a species native to sub-Saharan regions of Africa. We compare growth between cytotypes and test whether polyploid seedlings grow better than diploids. Our results show that polyploids coexist with diploids in highly variable proportions among populations in Senegal. Acacia senegal genotypes were predominantly diploid and tetraploid, but triploid, pentaploid, hexaploid, and octaploid forms were also found. We find that polyploids show faster growth than diploids under our test conditions: in an 18 years old field trial, polyploid superiority was estimated to be 17% in trunk diameter and 9% in height while in a growth chamber experiment, polyploids grew 28% taller, but only after being exposed to drought stress. The results suggest that polyploid A. senegal can have an adaptive advantage in some regions of Africa. PMID- 27379121 TI - Digital Gene Expression Analysis of Populus simonii * P. nigra Pollen Germination and Tube Growth. AB - Pollen tubes are an ideal model for the study of cell growth and morphogenesis because of their extreme elongation without cell division; however, the genetic basis of pollen germination and tube growth remains largely unknown. Using the Illumina/Solexa digital gene expression system, we identified 13,017 genes (representing 28.3% of the unigenes on the reference genes) at three stages, including mature pollen, hydrated pollen, and pollen tubes of Populus simonii * P. nigra. Comprehensive analysis of P. simonii * P. nigra pollen revealed dynamic changes in the transcriptome during pollen germination and pollen tube growth (PTG). Gene ontology analysis of differentially expressed genes showed that genes involved in functional categories such as catalytic activity, binding, transporter activity, and enzyme regulator activity were overrepresented during pollen germination and PTG. Some highly dynamic genes involved in pollen germination and PTG were detected by clustering analysis. Genes related to some key pathways such as the mitogen-activated protein kinase signaling pathway, regulation of the actin cytoskeleton, calcium signaling, and ubiquitin-mediated proteolysis were significantly changed during pollen germination and PTG. These data provide comprehensive molecular information toward further understanding molecular mechanisms underlying pollen germination and PTG. PMID- 27379122 TI - Floral Nectary Morphology and Proteomic Analysis of Nectar of Liriodendron tulipifera Linn. AB - Nectar is a primary nutrient reward for a variety of pollinators. Recent studies have demonstrated that nectar also has defensive functions against microbial invasion. In this study, the Liriodendron tulipifera nectary was first examined by scanning electron microscopy, and then the nectar was analyzed by two dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry, which led to identification of 42 nectar proteins involved in various biological functions. Bioinformatic analysis was then performed on an identified novel rubber elongation factor (REF) protein in L. tulipifera nectar. The protein was particularly abundant, representing ~60% of the major bands of 31 to 43 kDa, and showed high, stage-specific expression in nectary tissue. The REF family proteins are the major allergens in latex. We propose that REF in L. tulipifera nectar has defensive characteristics against microorganisms. PMID- 27379123 TI - The RNA Structure of cis-acting Translational Elements of the Chloroplast psbC mRNA in Chlamydomonas reinhardtii. AB - Photosystem II is the first of two light-driven oxidoreductase complexes in oxygenic photosynthesis. The biogenesis of photosystem II requires the synthesis of polypeptide subunits encoded by the genomes in the chloroplast and the nucleus. In the chloroplast of the green alga Chlamydomonas reinhardtii, the synthesis of each subunit requires interactions between the 5' UTR of the mRNA encoding it and gene-specific translation factors. Here, we analyze the sequences and structures in the 5' UTR of the psbC mRNA, which are known to be required to promote translation and genetic interaction with TBC1, a nuclear gene required specifically for psbC translation. Results of enzymatic probing in vitro and chemical probing in vivo and in vitro support three secondary structures and reveal that one participates in a pseudoknot structure. Analyses of the effects of mutations affecting pseudoknot sequences, by structural mapping and thermal gradient gel electrophoresis, reveal that flexibility at the base of the major stem-loop is required for translation and higher order RNA conformation, and suggest that this conformation is stabilized by TBC1. This RNA pseudoknot tertiary structure is analogous to the internal ribosome entry sites that promote translation of certain viruses and cellular mRNAs in the nuclear-cytoplasmic systems of eukaryotes. PMID- 27379124 TI - Characterization of Pearl Millet Root Architecture and Anatomy Reveals Three Types of Lateral Roots. AB - Pearl millet plays an important role for food security in arid regions of Africa and India. Nevertheless, it is considered an orphan crop as it lags far behind other cereals in terms of genetic improvement efforts. Breeding pearl millet varieties with improved root traits promises to deliver benefits in water and nutrient acquisition. Here, we characterize early pearl millet root system development using several different root phenotyping approaches that include rhizotrons and microCT. We report that early stage pearl millet root system development is characterized by a fast growing primary root that quickly colonizes deeper soil horizons. We also describe root anatomical studies that revealed three distinct types of lateral roots that form on both primary roots and crown roots. Finally, we detected significant variation for two root architectural traits, primary root lenght and lateral root density, in pearl millet inbred lines. This study provides the basis for subsequent genetic experiments to identify loci associated with interesting early root development traits in this important cereal. PMID- 27379125 TI - Comparative Cuticle Development Reveals Taller Sporophytes Are Covered by Thicker Calyptra Cuticles in Mosses. AB - The calyptra is a maternal structure that protects the sporophyte offspring from dehydration, and positively impacts sporophyte survival and fitness in mosses. We explore the relationship between cuticle protection and sporophyte height as a proxy for dehydration stress in Funariaceae species with sporophytes across a range of sizes. Calyptrae and sporophytes from four species were collected from laboratory-grown populations at two developmental stages. Tissues were embedded, sectioned, and examined using transmission electron microscopy. Cuticle thickness was measured from three epidermal cells per organ for each individual and compared statistically. All four species have cuticles consisting of a cuticle proper and a cuticular layer on the calyptra and sporophyte at both developmental stages. Across species, shorter sporophytes are associated with smaller calyptra and thinner calyptra cuticles, whereas taller sporophytes are associated with larger calyptra and thicker calyptra cuticles. Independent of size, young sporophytes have a thin cuticle that thickens later during development, while calyptrae have a mature cuticle produced early during development that persists throughout development. This study adds to our knowledge of maternal effects influencing offspring survival in plants. Released from the pressures to invest in protection for their sporophyte offspring, maternal resources can be allocated to other processes that support sporophyte reproductive success. Using a comparative developmental framework enables us to broaden our understanding of cuticle development across species and provides structural evidence supporting the waterproofing role of the moss calyptra. PMID- 27379126 TI - Combined Linkage and Association Mapping Reveals QTL and Candidate Genes for Plant and Ear Height in Maize. AB - Plant height (PH) and ear height (EH) are two very important agronomic traits related to the population density and lodging in maize. In order to better understand of the genetic basis of nature variation in PH and EH, two bi-parental populations and one genome-wide association study (GWAS) population were used to map quantitative trait loci (QTL) for both traits. Phenotypic data analysis revealed a wide normal distribution and high heritability for PH and EH in the three populations, which indicated that maize height is a highly polygenic trait. A total of 21 QTL for PH and EH in three common genomic regions (bin 1.05, 5.04/05, and 6.04/05) were identified by QTL mapping in the two bi-parental populations under multiple environments. Additionally, 41 single nucleotide polymorphisms (SNPs) were identified for PH and EH by GWAS, of which 29 SNPs were located in 19 unique candidate gene regions. Most of the candidate genes were related to plant growth and development. One QTL on Chromosome 1 was further verified in a near-isogenic line (NIL) population, and GWAS identified a C2H2 zinc finger family protein that maybe the candidate gene for this QTL. These results revealed that nature variation of PH and EH are strongly controlled by multiple genes with low effect and facilitated a better understanding of the underlying mechanism of height in maize. PMID- 27379127 TI - Polyamine Resistance Is Increased by Mutations in a Nitrate Transporter Gene NRT1.3 (AtNPF6.4) in Arabidopsis thaliana. AB - Polyamines are small basic compounds present in all living organisms and act in a variety of biological processes. However, the mechanism of polyamine sensing, signaling and response in relation to other metabolic pathways remains to be fully addressed in plant cells. As one approach, we isolated Arabidopsis mutants that show increased resistance to spermine in terms of chlorosis. We show here that two of the mutants have a point mutation in a nitrate transporter gene of the NRT1/PTR family (NPF), NRT1.3 (AtNPF6.4). These mutants also exhibit increased resistance to putrescine and spermidine while loss-of-function mutants of the two closest homologs of NRT1.3, root-specific NRT1.1 (AtNPF6.3) and petiole-specific NRT1.4 (AtNPF6.2), were shown to have a normal sensitivity to polyamines. When the GUS reporter gene was expressed under the control of the NRT1.3 promoter, GUS staining was observed in leaf mesophyll cells and stem cortex cells but not in the epidermis, suggesting that NRT1.3 specifically functions in parenchymal tissues. We further found that the aerial part of the mutant seedling has normal levels of polyamines but shows reduced uptake of norspermidine compared with the wild type. These results suggest that polyamine transport or metabolism is associated with nitrate transport in the parenchymal tissue of the shoot. PMID- 27379128 TI - Mixed Nodule Infection in Sinorhizobium meliloti-Medicago sativa Symbiosis Suggest the Presence of Cheating Behavior. AB - In the symbiosis between rhizobia and legumes, host plants can form symbiotic root nodules with multiple rhizobial strains, potentially showing different symbiotic performances in nitrogen fixation. Here, we investigated the presence of mixed nodules, containing rhizobia with different degrees of mutualisms, and evaluate their relative fitness in the Sinorhizobium meliloti-Medicago sativa model symbiosis. We used three S. meliloti strains, the mutualist strains Rm1021 and BL225C and the non-mutualist AK83. We performed competition experiments involving both in vitro and in vivo symbiotic assays with M. sativa host plants. We show the occurrence of a high number (from 27 to 100%) of mixed nodules with no negative effect on both nitrogen fixation and plant growth. The estimation of the relative fitness as non-mutualist/mutualist ratios in single nodules shows that in some nodules the non-mutualist strain efficiently colonized root nodules along with the mutualist ones. In conclusion, we can support the hypothesis that in S. meliloti-M. sativa symbiosis mixed nodules are formed and allow non mutualist or less-mutualist bacterial partners to be less or not sanctioned by the host plant, hence allowing a potential form of cheating behavior to be present in the nitrogen fixing symbiosis. PMID- 27379129 TI - Root Herbivores Drive Changes to Plant Primary Chemistry, but Root Loss Is Mitigated under Elevated Atmospheric CO2. AB - Above- and belowground herbivory represents a major challenge to crop productivity and sustainable agriculture worldwide. How this threat from multiple herbivore pests will change under anthropogenic climate change, via altered trophic interactions and plant response traits, is key to understanding future crop resistance to herbivory. In this study, we hypothesized that atmospheric carbon enrichment would increase the amount (biomass) and quality (C:N ratio) of crop plant resources for above- and belowground herbivore species. In a controlled environment facility, we conducted a microcosm experiment using the large raspberry aphid (Amphorophora idaei), the root feeding larvae of the vine weevil (Otiorhynchus sulcatus), and the raspberry (Rubus idaeus) host-plant. There were four herbivore treatments (control, aphid only, weevil only and a combination of both herbivores) and an ambient (aCO2) or elevated (eCO2) CO2 treatment (390 versus 650 +/- 50 MUmol/mol) assigned to two raspberry cultivars (cv Glen Ample or Glen Clova) varying in resistance to aphid herbivory. Contrary to our predictions, eCO2 did not increase crop biomass or the C:N ratio of the plant tissues, nor affect herbivore abundance either directly or via the host plant. Root herbivory reduced belowground crop biomass under aCO2 but not eCO2, suggesting that crops could tolerate attack in a CO2 enriched environment. Root herbivory also increased the C:N ratio in leaf tissue at eCO2, potentially due to decreased N uptake indicated by lower N concentrations found in the roots. Root herbivory greatly increased root C concentrations under both CO2 treatments. Our findings confirm that responses of crop biomass and biochemistry to climate change need examining within the context of herbivory, as biotic interactions appear as important as direct effects of eCO2 on crop productivity. PMID- 27379130 TI - Accumulation of Flavonols over Hydroxycinnamic Acids Favors Oxidative Damage Protection under Abiotic Stress. AB - Efficient detoxification of reactive oxygen species (ROS) is thought to play a key role in enhancing the tolerance of plants to abiotic stresses. Although multiple pathways, enzymes, and antioxidants are present in plants, their exact roles during different stress responses remain unclear. Here, we report on the characterization of the different antioxidant mechanisms of tomato plants subjected to heat stress, salinity stress, or a combination of both stresses. All the treatments applied induced an increase of oxidative stress, with the salinity treatment being the most aggressive, resulting in plants with the lowest biomass, and the highest levels of H2O2 accumulation, lipid peroxidation, and protein oxidation. However, the results obtained from the transcript expression study and enzymatic activities related to the ascorbate-glutathione pathway did not fully explain the differences in the oxidative damage observed between salinity and the combination of salinity and heat. An exhaustive metabolomics study revealed the differential accumulation of phenolic compounds depending on the type of abiotic stress applied. An analysis at gene and enzyme levels of the phenylpropanoid metabolism concluded that under conditions where flavonols accumulated to a greater degree as compared to hydroxycinnamic acids, the oxidative damage was lower, highlighting the importance of flavonols as powerful antioxidants, and their role in abiotic stress tolerance. PMID- 27379131 TI - Canavanine Alters ROS/RNS Level and Leads to Post-translational Modification of Proteins in Roots of Tomato Seedlings. AB - Canavanine (CAN), a structural analog of arginine (Arg), is used as a selective inhibitor of inducible NOS in mammals. CAN is incorporated into proteins' structure in the place of Arg, leading to the formation of aberrant compounds. This non-protein amino acid is found in legumes, e.g., Canavalia ensiformis (L.) DC. or Sutherlandia frutescens (L.) R.Br. and acts as a strong toxin against herbivores or plants. Tomato (Solanum lycopersicum L.) seedlings were treated for 24-72 h with CAN (10 or 50 MUM) inhibiting root growth by 50 or 100%, without lethal effect. We determined ROS level/production in root extracts, fluorescence of DAF-FM and APF derivatives corresponding to RNS level in roots of tomato seedlings and linked CAN-induced restriction of root growth to the post translational modifications (PTMs) of proteins: carbonylation and nitration. Both PTMs are stable markers of nitro-oxidative stress, regarded as the plant's secondary response to phytotoxins. CAN enhanced H2O2 content and superoxide radicals generation in extracts of tomato roots and stimulated formation of protein carbonyl groups. An elevated level of carbonylated proteins was characteristic for the plants after 72 h of the culture, mainly for the roots exposed to 10 MUM CAN. The proteolytic activity was stimulated by tested non protein amino acid. CAN treatment led to decline of fluorescence of DAF-FM derivatives, and transiently stimulated fluorescence of APF derivatives. Short term exposure of tomato seedlings to CAN lowered the protein nitration level. Activity of peroxidase, polyamine oxidase and NADPH oxidase, enzymes acting as modulators of H2O2 concentration and governing root architecture and growth were determined. Activities of all enzymes were stimulated by CAN, but no strict CAN concentration dependence was observed. We conclude, that although CAN treatment led to a decline in the nitric oxide level, PTMs observed in roots of plants exposed to CAN are linked rather to the formation of carbonyl groups than to nitration, and are detected particularly after 24 h. Thus, oxidative stress and oxidative modifications of proteins seems to be of significant importance in the rapid response of plants to CAN. PMID- 27379132 TI - Complete Chloroplast Genome of Nicotiana otophora and its Comparison with Related Species. AB - Nicotiana otophora is a wild parental species of Nicotiana tabacum, an interspecific hybrid of Nicotiana tomentosiformis and Nicotiana sylvestris. However, N. otophora is least understood as an alternative paternal donor. Here, we compared the fully assembled chloroplast (cp) genome of N. otophora and with those of closely related species. The analysis showed a cp genome size of 156,073 bp and exhibited a typical quadripartite structure, which contains a pair of inverted repeats separated by small and large single copies, containing 163 representative genes, with 165 microsatellites distributed unevenly throughout the genome. Comparative analysis of a gene with known function across Nicotiana species revealed 76 protein-coding sequences, 20 tRNA sequences, and 3 rRNA sequence shared between the cp genomes. The analysis revealed that N. otophora is a sister species to N. tomentosiformis within the Nicotiana genus, and Atropha belladonna and Datura stramonium are their closest relatives. These findings provide a valuable analysis of the complete N. otophora cp genome, which can identify species, elucidate taxonomy, and reconstruct the phylogeny of genus Nicotiana. PMID- 27379133 TI - Effects of Intercropping with Potato Onion on the Growth of Tomato and Rhizosphere Alkaline Phosphatase Genes Diversity. AB - BACKGROUND AND AIMS: In China, excessive fertilization has resulted in phosphorus (P) accumulation in most greenhouse soils. Intercropping can improve the efficiency of nutrient utilization in crop production. In this study, pot experiments were performed to investigate the effects of intercropping with potato onion (Allium cepa L. var. aggregatum G. Don) on tomato (Solanum lycopersicum L.) seedlings growth and P uptake, the diversity of rhizosphere phosphobacteria and alkaline phosphatase (ALP) genes in phosphorus-rich soil. METHODS: The experiment included three treatments, namely tomato monoculture (TM), potato onion monoculture (OM), and tomato/potato onion intercropping (TI tomato intercropping and OI-potato onion intercropping). The growth and P uptake of tomato and potato onion seedlings were evaluated. The dilution plating method was used to determine the population of phosphate-solubilizing bacteria (PSB) and phosphate-mineralizing bacteria (PMB). The genomic DNAs of PSB and PMB in the rhizosphere of tomato and potato onions were extracted and purified, and then, with the primer set of 338f /518r, the PCR amplification of partial bacterial 16S rDNA sequence was performed and sequenced to determine the diversities of PSB and PMB. After extracting the total genomic DNAs from the rhizosphere, the copy numbers and diversities of ALP genes were investigated using real-time PCR and PCR-DGGE, respectively. RESULTS: Intercropping with potato onion promoted the growth and P uptake of tomato seedlings, but inhibited those of potato onion. After 37 days of transplanting, compared to the rhizosphere of TM, the soil pH increased, while the electrolytic conductivity and Olsen P content decreased (p < 0.05) in the rhizosphere of TI. The populations and diversities of PSB, PMB, and ALP genes increased significantly in the rhizosphere of TI, compared to the rhizosphere of TM. CONCLUSION: The results indicated that intercropping with potato onion promoted the growth and P uptake of tomato in phosphorus-rich soil and affected the community structure and function of phosphobacteria in tomato rhizosphere. Intercropping with potato onion also improved soil quality by lowering levels of soil acidification and salinization. PMID- 27379135 TI - Reference Genes for qPCR Analysis in Resin-Tapped Adult Slash Pine As a Tool to Address the Molecular Basis of Commercial Resinosis. AB - Pine oleoresin is a major source of terpenes, consisting of turpentine (mono- and sesquiterpenes) and rosin (diterpenes) fractions. Higher oleoresin yields are of economic interest, since oleoresin derivatives make up a valuable source of materials for chemical industries. Oleoresin can be extracted from living trees, often by the bark streak method, in which bark removal is done periodically, followed by application of stimulant paste containing sulfuric acid and other chemicals on the freshly wounded exposed surface. To better understand the molecular basis of chemically-stimulated and wound induced oleoresin production, we evaluated the stability of 11 putative reference genes for the purpose of normalization in studying Pinus elliottii gene expression during oleoresinosis. Samples for RNA extraction were collected from field-grown adult trees under tapping operations using stimulant pastes with different compositions and at various time points after paste application. Statistical methods established by geNorm, NormFinder, and BestKeeper softwares were consistent in pointing as adequate reference genes HISTO3 and UBI. To confirm expression stability of the candidate reference genes, expression profiles of putative P. elliottii orthologs of resin biosynthesis-related genes encoding Pinus contorta beta-pinene synthase [PcTPS-(-)beta-pin1], P. contorta levopimaradiene/abietadiene synthase (PcLAS1), Pinus taeda alpha-pinene synthase [PtTPS-(+)alphapin], and P. taeda alpha farnesene synthase (PtalphaFS) were examined following stimulant paste application. Increased oleoresin yields observed in stimulated treatments using phytohormone-based pastes were consistent with higher expression of pinene synthases. Overall, the expression of all genes examined matched the expected profiles of oleoresin-related transcript changes reported for previously examined conifers. PMID- 27379134 TI - The Photosynthesis, Na(+)/K(+) Homeostasis and Osmotic Adjustment of Atriplex canescens in Response to Salinity. AB - Atriplex canescens (fourwing saltbush) is a C4 perennial fodder shrub with excellent resistance to salinity. However, the mechanisms underlying the salt tolerance in A. canescens are poorly understood. In this study, 5-weeks-old A. canescens seedlings were treated with various concentrations of external NaCl (0 400 mM). The results showed that the growth of A. canescens seedlings was significantly stimulated by moderate salinity (100 mM NaCl) and unaffected by high salinity (200 or 400 mM NaCl). Furthermore, A. canescens seedlings showed higher photosynthetic capacity under NaCl treatments (except for 100 mM NaCl treatment) with significant increases in net photosynthetic rate and water use efficiency. Under saline conditions, the A. canescens seedlings accumulated more Na(+) in either plant tissues or salt bladders, and also retained relatively constant K(+) in leaf tissues and bladders by enhancing the selective transport capacity for K(+) over Na(+) (ST value) from stem to leaf and from leaf to bladder. External NaCl treatments on A. canescens seedlings had no adverse impact on leaf relative water content, and this resulted from lower leaf osmotic potential under the salinity conditions. The contribution of Na(+) to the leaf osmotic potential (Psis) was sharply enhanced from 2% in control plants to 49% in plants subjected to 400 mM NaCl. However, the contribution of K(+) to Psis showed a significant decrease from 34% (control) to 9% under 400 mM NaCl. Interestingly, concentrations of betaine and free proline showed significant increase in the leaves of A. canescens seedlings, these compatible solutes presented up to 12% of contribution to Psis under high salinity. These findings suggest that, under saline environments, A. canescens is able to enhance photosynthetic capacity, increase Na(+) accumulation in tissues and salt bladders, maintain relative K(+) homeostasis in leaves, and use inorganic ions and compatible solutes for osmotic adjustment which may contribute to the improvement of water status in plant. PMID- 27379136 TI - Oligouridylate Binding Protein 1b Plays an Integral Role in Plant Heat Stress Tolerance. AB - Stress granules (SGs), which are formed in the plant cytoplasm under stress conditions, are transient dynamic sites (particles) for mRNA storage. SGs are actively involved in protecting mRNAs from degradation. Oligouridylate binding protein 1b (UBP1b) is a component of SGs. The formation of microscopically visible cytoplasmic foci, referred to as UBP1b SG, was induced by heat treatment in UBP1b-overexpressing Arabidopsis plants (UBP1b-ox). A detailed understanding of the function of UBP1b, however, is still not clear. UBP1b-ox plants displayed increased heat tolerance, relative to control plants, while ubp1b mutants were more sensitive to heat stress than control plants. Microarray analysis identified 117 genes whose expression was heat-inducible and higher in the UBP1b-ox plants. RNA decay analysis was performed using cordycepin, a transcriptional inhibitor. In order to determine if those genes serve as targets of UBP1b, the rate of RNA degradation of a DnaJ heat shock protein and a stress-associated protein (AtSAP3) in UBP1b-ox plants was slower than in control plants; indicating that the mRNAs of these genes were protected within the UBP1b SG granule. Collectively, these data demonstrate that UBP1b plays an integral role in heat stress tolerance in plants. PMID- 27379137 TI - QTLs Regulating the Contents of Antioxidants, Phenolics, and Flavonoids in Soybean Seeds Share a Common Genomic Region. AB - Soybean seeds are a rich source of phenolic compounds, especially isoflavonoids, which are important nutraceuticals. Our study using 14 wild- and 16 cultivated soybean accessions shows that seeds from cultivated soybeans generally contain lower total antioxidants compared to their wild counterparts, likely an unintended consequence of domestication or human selection. Using a recombinant inbred population resulting from a wild and a cultivated soybean parent and a bin map approach, we have identified an overlapping genomic region containing major quantitative trait loci (QTLs) that regulate the seed contents of total antioxidants, phenolics, and flavonoids. The QTL for seed antioxidant content contains 14 annotated genes based on the Williams 82 reference genome (Gmax1.01). None of these genes encodes functions that are related to the phenylpropanoid pathway of soybean. However, we found three putative Multidrug And Toxic Compound Extrusion (MATE) transporter genes within this QTL and one adjacent to it (GmMATE1-4). Moreover, we have identified non-synonymous changes between GmMATE1 and GmMATE2, and that GmMATE3 encodes an antisense transcript that expresses in pods. Whether the polymorphisms in GmMATE proteins are major determinants of the antioxidant contents, or whether the antisense transcripts of GmMATE3 play important regulatory roles, awaits further functional investigations. PMID- 27379138 TI - Transcriptome Profiling Revealed Stress-Induced and Disease Resistance Genes Up Regulated in PRSV Resistant Transgenic Papaya. AB - Papaya is a productive and nutritious tropical fruit. Papaya Ringspot Virus (PRSV) is the most devastating pathogen threatening papaya production worldwide. Development of transgenic resistant varieties is the most effective strategy to control this disease. However, little is known about the genome-wide functional changes induced by particle bombardment transformation. We conducted transcriptome sequencing of PRSV resistant transgenic papaya SunUp and its PRSV susceptible progenitor Sunset to compare the transcriptional changes in young healthy leaves prior to infection with PRSV. In total, 20,700 transcripts were identified, and 842 differentially expressed genes (DEGs) randomly distributed among papaya chromosomes. Gene ontology (GO) category analysis revealed that microtubule-related categories were highly enriched among these DEGs. Numerous DEGs related to various transcription factors, transporters and hormone biosynthesis showed clear differences between the two cultivars, and most were up regulated in transgenic papaya. Many known and novel stress-induced and disease resistance genes were most highly expressed in SunUp, including MYB, WRKY, ERF, NAC, nitrate and zinc transporters, and genes involved in the abscisic acid, salicylic acid, and ethylene signaling pathways. We also identified 67,686 alternative splicing (AS) events in Sunset and 68,455 AS events in SunUp, mapping to 10,994 and 10,995 papaya annotated genes, respectively. GO enrichment for the genes displaying AS events exclusively in Sunset was significantly different from those in SunUp. Transcriptomes in Sunset and transgenic SunUp are very similar with noteworthy differences, which increased PRSV-resistance in transgenic papaya. No detrimental pathways and allergenic or toxic proteins were induced on a genome-wide scale in transgenic SunUp. Our results provide a foundation for unraveling the mechanism of PRSV resistance in transgenic papaya. PMID- 27379139 TI - Evaluation of Three Protein-Extraction Methods for Proteome Analysis of Maize Leaf Midrib, a Compound Tissue Rich in Sclerenchyma Cells. AB - Leaf morphology is closely related to the growth and development of maize (Zea mays L.) plants and final kernel production. As an important part of the maize leaf, the midrib holds leaf blades in the aerial position for maximum sunlight capture. Leaf midribs of adult plants contain substantial sclerenchyma cells with heavily thickened and lignified secondary walls and have a high amount of phenolics, making protein extraction and proteome analysis difficult in leaf midrib tissue. In the present study, three protein-extraction methods that are commonly used in plant proteomics, i.e., phenol extraction, TCA/acetone extraction, and TCA/acetone/phenol extraction, were qualitatively and quantitatively evaluated based on 2DE maps and MS/MS analysis using the midribs of the 10th newly expanded leaves of maize plants. Microscopy revealed the existence of substantial amounts of sclerenchyma underneath maize midrib epidermises (particularly abaxial epidermises). The spot-number order obtained via 2DE mapping was as follows: phenol extraction (655) > TCA/acetone extraction (589) > TCA/acetone/phenol extraction (545). MS/MS analysis identified a total of 17 spots that exhibited 2-fold changes in abundance among the three methods (using phenol extraction as a control). Sixteen of the proteins identified were hydrophilic, with GRAVY values ranging from -0.026 to -0.487. For all three methods, we were able to obtain high-quality protein samples and good 2DE maps for the maize leaf midrib. However, phenol extraction produced a better 2DE map with greater resolution between spots, and TCA/acetone extraction produced higher protein yields. Thus, this paper includes a discussion regarding the possible reasons for differential protein extraction among the three methods. This study provides useful information that can be used to select suitable protein extraction methods for the proteome analysis of recalcitrant plant tissues that are rich in sclerenchyma cells. PMID- 27379140 TI - Root Architecture Diversity and Meristem Dynamics in Different Populations of Arabidopsis thaliana. AB - Arabidopsis thaliana has been an excellent model system for molecular genetic approaches to development and physiology. More recently, the potential of studying various accessions collected from diverse habitats has been started to exploit. Col-0 has been the best-studied accession but we now know that several traits show significant divergences among them. In this work, we focused in the root that has become a key system for development. We studied root architecture and growth dynamics of 12 Arabidopsis accessions. Our data reveal a wide variability in root architecture and root length among accessions. We also found variability in the root apical meristem (RAM), explained mainly by cell size at the RAM transition domain and possibly by peculiar forms of organization at the stem cell niche in some accessions. Contrary to Col-0 reports, in some accessions the RAM size not always explains the variations in the root length; indicating that elongated cell size could be more relevant in the determination of root length than the RAM size itself. This study contributes to investigations dealing with understanding the molecular and cellular basis of phenotypic variation, the role of plasticity on adaptation, and the developmental mechanisms that may restrict phenotypic variation in response to contrasting environmental conditions. PMID- 27379141 TI - An Alternative Pathway for Formononetin Biosynthesis in Pueraria lobata. AB - The O-methylation is an important tailing process in Pueraria lobata isoflavone metabolism, but the molecular mechanism governing it remains not elucidated. This manuscript describes the mining of key O-methyltransferases (OMTs) involved in the process. Using our previously constructed P. lobata transcriptome, the OMT candidates were searched, extensively analyzed, and their functions were investigated by expression in yeast, Escherichia coli, or Glycine max hairy roots. Here, we report the identification of the key OMT gene responsible for formononetin production in P. lobata (designated as PlOMT9). PlOMT9 primarily functions as an isoflavone-specific 4'-O-methyltransferase, although it shows high sequence identities with isoflavone 7-O-methyltransferases. Moreover, unlike the previously reported OMTs that catalyze the 4'-O-methylation for formononetin biosynthesis at the isoflavanone stage, PlOMT9 performs this modifying step at the isoflavone level, using daidzein rather than 2,7,4'-trihydroxy-isoflavanone as the substrate. Gene expression analyses and metabolite profiling supported its proposed roles in P. lobata. Using the system of transgenic G. max hairy roots, the role of PlOMT9 in the biosynthesis of formononetin was further demonstrated in vivo. PMID- 27379142 TI - The Aquaporin Splice Variant NbXIP1;1alpha Is Permeable to Boric Acid and Is Phosphorylated in the N-terminal Domain. AB - Aquaporins (AQPs) are membrane channel proteins that transport water and uncharged solutes across different membranes in organisms in all kingdoms of life. In plants, the AQPs can be divided into seven different subfamilies and five of these are present in higher plants. The most recently characterized of these subfamilies is the XIP subfamily, which is found in most dicots but not in monocots. In this article, we present data on two different splice variants (alpha and beta) of NbXIP1;1 from Nicotiana benthamiana. We describe the heterologous expression of NbXIP1;1alpha and beta in the yeast Pichia pastoris, the subcellular localization of the protein in this system and the purification of the NbXIP1;1alpha protein. Furthermore, we investigated the functionality and the substrate specificity of the protein by stopped-flow spectrometry in P. pastoris spheroplasts and with the protein reconstituted in proteoliposomes. The phosphorylation status of the protein and localization of the phosphorylated amino acids were verified by mass spectrometry. Our results show that NbXIP1;1alpha is located in the plasma membrane when expressed in P. pastoris, that it is not permeable to water but to boric acid and that the protein is phosphorylated at several amino acids in the N-terminal cytoplasmic domain of the protein. A growth assay showed that the yeast cells expressing the N-terminally His-tagged NbXIP1;1alpha were more sensitive to boric acid as compared to the cells expressing the C-terminally His-tagged isoform. This might suggest that the N-terminal His-tag functionally mimics the phosphorylation of the N-terminal domain and that the N-terminal domain is involved in gating of the channel. PMID- 27379143 TI - The Transcription Factor AtDOF4.7 Is Involved in Ethylene- and IDA-Mediated Organ Abscission in Arabidopsis. AB - Organ abscission is an important plant developmental process that occurs in response to environmental stress or pathogens. In Arabidopsis, ligand signals, such as ethylene or INFLORESCENCE DEFICIENT IN ABSCISSION (IDA), can regulate organ abscission. Previously, we reported that overexpression of AtDOF4.7, a transcription factor gene, directly suppresses the expression of the abscission related gene ARABIDOPSIS DEHISCENCE ZONE POLYGALACTURONASE 2 (ADPG2), resulting in a deficiency of floral organ abscission. However, the relationship between AtDOF4.7 and abscission pathways still needs to be investigated. In this study, we showed that ethylene regulates the expression of AtDOF4.7, and the peptide ligand, IDA negatively regulates AtDOF4.7 at the transcriptional level. Genetic evidence indicates that AtDOF4.7 and IDA are involved in a common pathway, and a MAPK cascade can phosphorylate AtDOF4.7 in vitro. Further in vivo data suggest that AtDOF4.7 protein levels may be regulated by this phosphorylation. Collectively, our results indicate that ethylene regulates AtDOF4.7 that is involved in the IDA-mediated floral organ abscission pathway. PMID- 27379144 TI - Phytohormones Signaling Pathways and ROS Involvement in Seed Germination. AB - Phytohormones and reactive oxygen species (ROS) are major determinants of the regulation of development and stress responses in plants. During life cycle of these organisms, signaling networks of plant growth regulators and ROS interact in order to render an appropriate developmental and environmental response. In plant's photosynthetic (e.g., leaves) and non-photosynthetic (e.g., seeds) tissues, enhanced and suboptimal ROS production is usually associated with stress, which in extreme cases can be lethal to cells, a whole organ or even an organism. However, controlled production of ROS is appreciated for cellular signaling. Despite the current progress that has been made in plant biology and increasing number of findings that have revealed roles of ROS and hormonal signaling in germination, some questions still arise, e.g., what are the downstream protein targets modified by ROS enabling stimulus-specific cellular responses of the seed? Or which molecular regulators allow ROS/phytohormones interactions and what is their function in seed life? In this particular review the role of some transcription factors, kinases and phosphatases is discussed, especially those which usually known to be involved in ROS and hormonal signal transduction under stress in plants, may also play a role in the regulation of processes occurring in seeds. The summarized recent findings regarding particular ROS- and phytohormones-related regulatory proteins, as well as their integration, allowed to propose a novel, possible model of action of LESION SIMULATING DISEASE 1, ENHANCED DISEASE SUSCEPTIBILITY 1, and PHYTOALEXIN DEFICIENT 4 functioning during seeds life. PMID- 27379145 TI - Vigorous Root Growth Is a Better Indicator of Early Nutrient Uptake than Root Hair Traits in Spring Wheat Grown under Low Fertility. AB - A number of root and root hair traits have been proposed as important for nutrient acquisition. However, there is still a need for knowledge on which traits are most important in determining macro- and micronutrient uptake at low soil fertility. This study investigated the variations in root growth vigor and root hair length (RHL) and density (RHD) among spring wheat genotypes and their relationship to nutrient concentrations and uptake during early growth. Six spring wheat genotypes were grown in a soil with low nutrient availability. The root and root hair traits as well as the concentration and content of macro- and micronutrients were identified. A significant genetic variability in root and root hair traits as well as nutrient uptake was found. Fast and early root proliferation and long and dense root hairs enhanced uptake of macro- and micronutrients under low soil nutrient availability. Vigorous root growth, however, was a better indicator of early nutrient acquisition than RHL and RHD. Vigorous root growth and long and dense root hairs ensured efficient acquisition of macro- and micronutrients during early growth and a high root length to shoot dry matter ratio favored high macronutrient concentrations in the shoots, which is assumed to be important for later plant development. PMID- 27379146 TI - Prolonged Soil Frost Affects Hydraulics and Phenology of Apple Trees. AB - Restoration of an adequate water supply in spring is a prerequisite for survival of angiosperm trees in temperate regions. Trees must re-establish access to soil water and recover xylem functionality. We thus hypothesized that prolonged soil frost impairs recovery and affects hydraulics and phenology of Malus domestica var. 'Golden Delicious.' To test this hypothesis, over two consecutive winters the soil around some trees was insulated to prolong soil frosting, From mid winter to early summer, the level of native embolism, the water and starch contents of wood, bark and buds were quantified at regular intervals and findings correlated with various phenological parameters, xylogenesis and fine root growth. The findings confirm that prolonged soil frost affects tree hydraulics and phenology but the severity of the effect depends on the climatic conditions. In both study years, percentage loss of hydraulic conductivity (PLC) decreased from about 70% at the end of winter to about 10% in May. Thereby, xylem refilling strongly coincided with a decrease of starch in wood and bark. Also treated trees were able to restore their hydraulic system by May but, in the warm spring of 2012, xylem refilling, the increases in water content and starch depolymerization were delayed. In contrast, in the cold spring of 2013 only small differences between control and treated trees were observed. Prolongation of soil frost also led to a delay in phenology, xylogenesis, and fine root growth. We conclude that reduced water uptake from frozen or cold soils impairs refilling and thus negatively impacts tree hydraulics and growth of apple trees in spring. Under unfavorable circumstances, this may cause severe winter damage or even dieback. PMID- 27379147 TI - Misannotation Awareness: A Tale of Two Gene-Groups. AB - Incorrectly or simply not annotated data is largely increasing in most public databases, undoubtedly caused by the rise in sequence data and the more recent boom of genomic projects. Molecular biologists and bioinformaticists should join efforts to tackle this issue. Practical challenges have been experienced when studying the alternative oxidase (AOX) gene family, and hence the motivation for the present work. Commonly used databases were screened for their capacity to distinguish AOX from the plastid terminal oxidase (also called plastoquinol terminal oxidase; PTOX) and we put forward a simple approach, based on amino acids signatures, that unequivocally distinguishes these gene families. Further, available sequence data on the AOX family in plants was carefully revised to: (1) confirm the classification as AOX and (2) identify to which AOX family member they belong to. We bring forward the urgent need of misannotation awareness and re-annotation of public AOX sequences by highlighting different types of misclassifications and the large under-estimation of data availability. PMID- 27379148 TI - Transcriptome Profile Analysis from Different Sex Types of Ginkgo biloba L. AB - In plants, sex determination is a comprehensive process of correlated events, which involves genes that are differentially and/or specifically expressed in distinct developmental phases. Exploring gene expression profiles from different sex types will contribute to fully understanding sex determination in plants. In this study, we conducted RNA-sequencing of female and male buds (FB and MB) as well as ovulate strobilus and staminate strobilus (OS and SS) of Ginkgo biloba to gain insights into the genes potentially related to sex determination in this species. Approximately 60 Gb of clean reads were obtained from eight cDNA libraries. De novo assembly of the clean reads generated 108,307 unigenes with an average length of 796 bp. Among these unigenes, 51,953 (47.97%) had at least one significant match with a gene sequence in the public databases searched. A total of 4709 and 9802 differentially expressed genes (DEGs) were identified in MB vs. FB and SS vs. OS, respectively. Genes involved in plant hormone signal and transduction as well as those encoding DNA methyltransferase were found to be differentially expressed between different sex types. Their potential roles in sex determination of G. biloba were discussed. Pistil-related genes were expressed in male buds while anther-specific genes were identified in female buds, suggesting that dioecism in G. biloba was resulted from the selective arrest of reproductive primordia. High correlation of expression level was found between the RNA-Seq and quantitative real-time PCR results. The transcriptome resources that we generated allowed us to characterize gene expression profiles and examine differential expression profiles, which provided foundations for identifying functional genes associated with sex determination in G. biloba. PMID- 27379149 TI - Triacontanol Reduces Transplanting Shock in Machine-Transplanted Rice by Improving the Growth and Antioxidant Systems. AB - Machine transplantation results in serious transplant shock in seedlings and results in a longer recover stage, which negatively impacts the growth of low position tillers and the yield of machine-transplanted rice. A barrel experiment was conducted to examine the effect of the foliar application of triacontanol (TRIA) on machine-transplanted rice during the recovery stage. TRIA (0, 1, 5, and 10 MUM) was sprayed over leaves 2 days before transplanting. The chlorophyll content, sucrose content, oxidative damage, antioxidant enzyme levels, glutathione (GSH), and ascorbate (ASA) redox states, tiller dynamics and yield components of the plants were investigated. The results show that foliar-applied TRIA significantly alleviates the growth inhibition and oxidative damage caused by transplant shock. Furthermore, the application of TRIA increased the chlorophyll and sucrose contents of the plants. Importantly, TRIA not only significantly improved the activity of catalase (CAT) and guaiacol peroxidase (POD), demonstrating that POD can play an important role in scavenging H2O2 during the recovery stage, but it also enhanced the redox states of ASA and GSH by regulating the activities of enzymes involved in the ASA-GSH cycle, such as ascorbate peroxidase (APX) and glutathione reductase (GR). A dose of 10 MUM TRIA was the most efficient in reducing the negative effects of transplant shock, increasing the panicles, grain filling, and grain yield per hill by 17.80, 5.86, and 16.49%, respectively. These results suggest that TRIA acts to reduce transplant shock in association with the regulation of the redox states of ASA and GSH and antioxidant enzymes and serves as an effective antioxidant to maintain photosynthetic capacity and promote the occurrence of low tillers. PMID- 27379150 TI - A Modeling Approach to Quantify the Effects of Stomatal Behavior and Mesophyll Conductance on Leaf Water Use Efficiency. AB - Water use efficiency (WUE) is considered as a determinant of yield under stress and a component of crop drought resistance. Stomatal behavior regulates both transpiration rate and net assimilation and has been suggested to be crucial for improving crop WUE. In this work, a dynamic model was used to examine the impact of dynamic properties of stomata on WUE. The model includes sub-models of stomatal conductance dynamics, solute accumulation in the mesophyll, mesophyll water content, and water flow to the mesophyll. Using the instantaneous value of stomatal conductance, photosynthesis, and transpiration rate were simulated using a biochemical model and Penman-Monteith equation, respectively. The model was parameterized for a cucumber leaf and model outputs were evaluated using climatic data. Our simulations revealed that WUE was higher on a cloudy than a sunny day. Fast stomatal reaction to light decreased WUE during the period of increasing light (e.g., in the morning) by up to 10.2% and increased WUE during the period of decreasing light (afternoon) by up to 6.25%. Sensitivity of daily WUE to stomatal parameters and mesophyll conductance to CO2 was tested for sunny and cloudy days. Increasing mesophyll conductance to CO2 was more likely to increase WUE for all climatic conditions (up to 5.5% on the sunny day) than modifications of stomatal reaction speed to light and maximum stomatal conductance. PMID- 27379151 TI - Plant Growth Promoting Rhizobacteria and Silicon Synergistically Enhance Salinity Tolerance of Mung Bean. AB - The present study explored the eco-friendly approach of utilizing plant-growth promoting rhizobacteria (PGPR) inoculation and foliar application of silicon (Si) to improve the physiology, growth, and yield of mung bean under saline conditions. We isolated 18 promising PGPR from natural saline soil in Saudi Arabia, and screened them for plant-growth-promoting activities. Two effective strains were selected from the screening trial, and were identified as Enterobacter cloacae and Bacillus drentensis using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry and 16S rRNA gene sequencing techniques, respectively. Subsequently, in a 2-year mung bean field trial, using a randomized complete block design with a split-split plot arrangement, we evaluated the two PGPR strains and two Si levels (1 and 2 kg ha( 1)), in comparison with control treatments, under three different saline irrigation conditions (3.12, 5.46, and 7.81 dS m(-1)). The results indicated that salt stress substantially reduced stomatal conductance, transpiration rate, relative water content (RWC), total chlorophyll content, chlorophyll a, chlorophyll b, carotenoid content, plant height, leaf area, dry biomass, seed yield, and salt tolerance index. The PGPR strains and Si levels independently improved all the aforementioned parameters. Furthermore, the combined application of the B. drentensis strain with 2 kg Si ha(-1) resulted in the greatest enhancement of mung bean physiology, growth, and yield. Overall, the results of this study provide important information for the benefit of the agricultural industry. PMID- 27379152 TI - A Modified Reverse One-Hybrid Screen Identifies Transcriptional Activation Domains in PHYTOCHROME-INTERACTING FACTOR 3. AB - Transcriptional activation domains (TADs) are difficult to predict and identify, since they are not conserved and have little consensus. Here, we describe a yeast based screening method that is able to identify individual amino acid residues involved in transcriptional activation in a high throughput manner. A plant transcriptional activator, PIF3 (phytochrome interacting factor 3), was fused to the yeast GAL4-DNA-binding Domain (BD), driving expression of the URA3 (Orotidine 5'-phosphate decarboxylase) reporter, and used for negative selection on 5 fluroorotic acid (5FOA). Randomly mutagenized variants of PIF3 were then selected for a loss or reduction in transcriptional activation activity by survival on FOA. In the process, we developed a strategy to eliminate false positives from negative selection that can be used for both reverse-1- and 2-hybrid screens. With this method we were able to identify two distinct regions in PIF3 with transcriptional activation activity, both of which are functionally conserved in PIF1, PIF4, and PIF5. Both are collectively necessary for full PIF3 transcriptional activity, but neither is sufficient to induce transcription autonomously. We also found that the TAD appear to overlap physically with other PIF3 functions, such as phyB binding activity and consequent phosphorylation. Our protocol should provide a valuable tool for identifying, analyzing and characterizing novel TADs in eukaryotic transcription factors, and thus potentially contribute to the unraveling of the mechanism underlying transcriptional activation. PMID- 27379153 TI - Rapid Identification of Officinal Akebiae Caulis and Its Toxic Adulterant Aristolochiae Manshuriensis Caulis (Aristolochia manshuriensis) by Loop-Mediated Isothermal Amplification. AB - Mu-tong (Akebiae Caulis) is a traditional Chinese medicine commonly used as a diuretic and antiphlogistic. A common adulterant of Mu-tong is Guan-mu-tong (Aristolochiae Manshuriensis Caulis), which is derived from the stem of Aristolochia manshuriensis Komarov, and contains carcinogenic aristolochic acids. We used an alternative technique, loop-mediated isothermal amplification (LAMP), to differentiate Mu-tong from Guan-mu-tong because LAMP is quick, highly sensitive, and specific. We designed a set of four common primers (G-F3, G-B3, G FIP, and G-BIP) and a loop primer (G-LB) for LAMP based on the internal transcribed spacer 2 sequence of Ar. manshuriensis. We successfully amplified the LAMP assays and visual detection occurred within 60 min at isothermal conditions of 65 degrees C. The LAMP reaction exhibited a tenfold increase in detection (4.22 pg/MUl DNA) over conventional polymerase chain reaction demonstrating that LAMP is a useful technique to detect Guan-mu-tong. We conclude that the LAMP technique is a potentially valuable safety control method for simple and efficient discrimination of Mu-tong from its adulterant Guan-mu-tong. PMID- 27379154 TI - Current Advances in the Metabolomics Study on Lotus Seeds. AB - Lotus (Nelumbo nucifera), which is distributed widely throughout Asia, Australia and North America, is an aquatic perennial that has been cultivated for over 2,000 years. It is very stimulating that almost all parts of lotus have been consumed as vegetable as well as food, especially the seeds. Except for the nutritive values of lotus, there has been increasing interest in its potential as functional food due to its rich secondary metabolites, such as flavonoids and alkaloids. Not only have these metabolites greatly contributed to the biological process of lotus seeds, but also have been reported to possess multiple health promoting effects, including antioxidant, anti-amnesic, anti-inflammatory, and anti-tumor activities. Thus, comprehensive metabolomic profiling of these metabolites is of key importance to help understand their biological activities, and other chemical biology features. In this context, this review will provide an update on the current technological platforms, and workflow associated with metabolomic studies on lotus seeds, as well as insights into the application of metabolomics for the improvement of food safety and quality, assisting breeding, and promotion of the study of metabolism and pharmacokinetics of lotus seeds; meanwhile it will also help explore new perspectives and outline future challenges in this fast-growing research subject. PMID- 27379155 TI - A Predictive Based Regression Algorithm for Gene Network Selection. AB - Gene selection has become a common task in most gene expression studies. The objective of such research is often to identify the smallest possible set of genes that can still achieve good predictive performance. To do so, many of the recently proposed classification methods require some form of dimension-reduction of the problem which finally provide a single model as an output and, in most cases, rely on the likelihood function in order to achieve variable selection. We propose a new prediction-based objective function that can be tailored to the requirements of practitioners and can be used to assess and interpret a given problem. Based on cross-validation techniques and the idea of importance sampling, our proposal scans low-dimensional models under the assumption of sparsity and, for each of them, estimates their objective function to assess their predictive power in order to select. Two applications on cancer data sets and a simulation study show that the proposal compares favorably with competing alternatives such as, for example, Elastic Net and Support Vector Machine. Indeed, the proposed method not only selects smaller models for better, or at least comparable, classification errors but also provides a set of selected models instead of a single one, allowing to construct a network of possible models for a target prediction accuracy level. PMID- 27379157 TI - Do Copy Number Changes in CACNA2D2, CACNA2D3, and CACNA1D Constitute a Predisposing Risk Factor for Alzheimer's Disease? AB - Dysregulation of calcium (Ca(2+)) homeostasis is now being recognized to be a key step in the pathogenesis of Alzheimer's disease (AD). Data from the literature, in particular the association between AD and polymorphism that interfere with Ca(2+) homeostasis indicates the presence of genetic factors in this process; further, presenilins mutations, which are known to cause the familial form of AD, are involved in the regulation of intracellular Ca(2+) stores. Here, we wish to draw attention to rare DNA copy number variations identified in two subjects with late-onset AD that led to partial or full duplication of genes that encode different subunits of the same type of voltage-gated Ca(2+) channels; these duplications of voltage-gated Ca(2+) channel genes is consistent with the critical role of calcium signaling in molecular processes underlying memory as has been demonstrated by several studies. PMID- 27379158 TI - Association of a SNP in SLC35F3 Gene with the Risk of Hypertension in a Chinese Han Population. AB - A recent study suggested that SLC35F3 which encoded a thiamine transporter was a new candidate gene for hypertension. The goal of this study was to investigate the association between the single-nucleotide polymorphisms (SNPs) in the SLC35F3 gene and hypertension in a Chinese population. Sanger sequencing was performed in 93 samples to find SNPs in coding regions and intron-exon boundaries in the SLC35F3 gene. We found eight genetic variants in the coding regions of SLC35F3 and subsequently genotyped a non-synonymous variant rs34032258 (C > G) in 1060 hypertension patients and 1467 controls. After adjusting for age and gender, multivariate analysis of covariance showed that the variant was associated with hypertensive traits. In detail, diastolic blood pressure (DBP) was 8 mmHg higher, blood urea nitrogen was 12 mmol/L higher, and creatinine was 15 mmol/L lower in G/G group compared with C/C group (p = 0.007; 0.012 and 0.029, respectively). Further study suggested that C/G+G/G had higher DBP than C/C genotype in those whose DBP >= 90 mmHg (98.02 mmHg vs. 94.04 mmHg, p = 0.021). No significant difference has been found in systolic blood pressure between different genotypes. Additionally, in the subgroup of obesity, allele distribution of this variant has shown significant difference between hypertensive patients and normotensive controls (p = 0.018). In conclusion, we found that the rs34032258 in the SLC35F3 gene was associated with high blood pressure and may increase the risk of hypertension. The new hypertension-susceptibility locus may involve in the pathogenesis of hypertension and indicate some novel treatment implications. PMID- 27379156 TI - The Regulation of DNA Damage Tolerance by Ubiquitin and Ubiquitin-Like Modifiers. AB - DNA replication is an extremely complex process that needs to be executed in a highly accurate manner in order to propagate the genome. This task requires the coordination of a number of enzymatic activities and it is fragile and prone to arrest after DNA damage. DNA damage tolerance provides a last line of defense that allows completion of DNA replication in the presence of an unrepaired template. One of such mechanisms is called post-replication repair (PRR) and it is used by the cells to bypass highly distorted templates caused by damaged bases. PRR is extremely important for the cellular life and performs the bypass of the damage both in an error-free and in an error-prone manner. In light of these two possible outcomes, PRR needs to be tightly controlled in order to prevent the accumulation of mutations leading ultimately to genome instability. Post-translational modifications of PRR proteins provide the framework for this regulation with ubiquitylation and SUMOylation playing a pivotal role in choosing which pathway to activate, thus controlling the different outcomes of damage bypass. The proliferating cell nuclear antigen (PCNA), the DNA clamp for replicative polymerases, plays a central role in the regulation of damage tolerance and its modification by ubiquitin, and SUMO controls both the error free and error-prone branches of PRR. Furthermore, a significant number of polymerases are involved in the bypass of DNA damage possess domains that can bind post-translational modifications and they are themselves target for ubiquitylation. In this review, we will focus on how ubiquitin and ubiquitin-like modifications can regulate the DNA damage tolerance systems and how they control the recruitment of different proteins to the replication fork. PMID- 27379159 TI - Mass Spectrometry-Based Proteomics for Investigating DNA Damage-Associated Protein Ubiquitylation. AB - Modification of proteins with the 76 amino acid protein ubiquitin plays essential roles in cellular signaling. Development of methods for specific enrichment of ubiquitin remnant peptides and advances in high-resolution mass spectrometry have enabled proteome-wide identification of endogenous ubiquitylation sites. Moreover, ubiquitin remnant profiling has emerged as a powerful approach for investigating changes in protein ubiquitylation in response to cellular perturbations, such as DNA damage, as well as for identification of substrates of ubiquitin-modifying enzymes. Despite these advances, interrogation of ubiquitin chain topologies on substrate proteins remains a challenging task. Here, we describe mass spectrometry-based approaches for quantitative analyses of site specific protein ubiquitylation and highlight recent studies that employed these methods for investigation of ubiquitylation in the context of the cellular DNA damage response. Furthermore, we provide an overview of experimental strategies for probing ubiquitin chain topologies on proteins and discuss how these methods can be applied to analyze functions of ubiquitylation in the DNA damage response. PMID- 27379161 TI - Editorial: Protein Interaction Networks in Health and Disease. PMID- 27379160 TI - Comparative Epigenomic Profiling of the DNA Methylome in Mouse and Zebrafish Uncovers High Interspecies Divergence. AB - The DNA methylation landscape is dynamically patterned during development and distinct methylation patterns distinguish healthy from diseased cells. However, whether tissue-specific methylation patterns are conserved across species is not known. We used comparative methylome analysis of base-resolution DNA methylation profiles from the liver and brain of mouse and zebrafish generated by reduced representation bisulfite sequencing to identify the conserved and divergent aspects of the methylome in these commonly used vertebrate model organisms. On average, 24% of CpGs are methylated in mouse livers and the pattern of methylation was highly concordant among four male mice from two different strains. The same level of methylation (24.2%) was identified in mouse brain. In striking contrast, zebrafish had 63 and 70% of CpG methylation in the liver and brain, respectively. This is attributed, in part, to the higher percentage of the zebrafish genome occupied by transposable elements (52% vs. 45% in mice). Thus, the species identity was more significant in determining methylome patterning than was the similarity in organ function. Conserved features of the methylome across tissues and species was the exclusion of methylation from promoters and from CpG islands near transcription start sites, and the clustering of methylated CpGs in gene bodies and intragenic regions. These data suggest that DNA methylation reflects species-specific genome structure, and supports the notion that DNA methylation in non-promoter regions may contribute to genome evolution. PMID- 27379162 TI - Protease-Activated Receptors and other G-Protein-Coupled Receptors: the Melanoma Connection. AB - The vast array of G-protein-coupled receptors (GPCRs) play crucial roles in both physiological and pathological processes, including vision, coagulation, inflammation, autophagy, and cell proliferation. GPCRs also affect processes that augment cell proliferation and metastases in many cancers including melanoma. Melanoma is the deadliest form of skin cancer, yet limited therapeutic modalities are available to patients with metastatic melanoma. Studies have found that both chemokine receptors and protease-activated receptors, both of which are GPCRs, are central to the metastatic melanoma phenotype and may serve as potential targets in novel therapies against melanoma and other cancers. PMID- 27379163 TI - Development of SSR Markers and Assessment of Genetic Diversity in Medicinal Chrysanthemum morifolium Cultivars. AB - Chrysanthemum morifolium, is a well-known flowering plant worldwide, and has a high commercial, floricultural, and medicinal value. In this study, simple sequence repeat (SSR) markers were generated from EST datasets and were applied to assess the genetic diversity among 32 cultivars. A total of 218 in silico SSR loci were identified from 7300 C. morifolium ESTs retrieved from GenBank. Of all SSR loci, 61.47% of them (134) were hexa-nucleotide repeats, followed by tri nucleotide repeats (17.89%), di-nucleotide repeats (12.39%), tetra-nucleotide repeats (4.13%), and penta-nucleotide repeats (4.13%). In this study, 17 novel EST-SSR markers were verified. Along with 38 SSR markers reported previously, 55 C. morifolium SSR markers were selected for further genetic diversity analysis. PCR amplification of these EST-SSRs produced 1319 fragments, 1306 of which showed polymorphism. The average polymorphism information content of the SSR primer pairs was 0.972 (0.938-0.993), which showed high genetic diversity among C. morifolium cultivars. Based on SSR markers, 32 C. morifolium cultivars were separated into two main groups by partitioning of the clusters using the unweighted pair group method with arithmetic mean dendrogram, which was further supported by a principal coordinate analysis plot. Phylogenetic relationship among C. morifolium cultivars as revealed by SSR markers was highly consistent with the classification of medicinal C. morifolium populations according to their origin and ecological distribution. Our results demonstrated that SSR markers were highly reproducible and informative, and could be used to evaluate genetic diversity and relationships among medicinal C. morifolium cultivars. PMID- 27379164 TI - Deriving Gene Networks from SNP Associated with Triacylglycerol and Phospholipid Fatty Acid Fractions from Ribeyes of Angus Cattle. AB - The fatty acid profile of beef is a complex trait that can benefit from gene interaction network analysis to understand relationships among loci that contribute to phenotypic variation. Phenotypic measures of fatty acid profile from triacylglycerol and phospholipid fractions of longissimus muscle, pedigree information, and Illumina 54 k bovine SNP genotypes were utilized to derive an annotated gene network associated with fatty acid composition in 1,833 Angus beef cattle. The Bayes-B statistical model was utilized to perform a genome wide association study to estimate associations between 54 k SNP genotypes and 39 individual fatty acid phenotypes within each fraction. Posterior means of the effects were estimated for each of the 54 k SNP and for the collective effects of all the SNP in every 1-Mb genomic window in terms of the proportion of genetic variance explained by the window. Windows that explained the largest proportions of genetic variance for individual lipids were found in the triacylglycerol fraction. There was almost no overlap in the genomic regions explaining variance between the triacylglycerol and phospholipid fractions. Partial correlations were used to identify correlated regions of the genome for the set of largest 1 Mb windows that explained up to 35% genetic variation in either fatty acid fraction. SNP were allocated to windows based on the bovine UMD3.1 assembly. Gene network clusters were generated utilizing a partial correlation and information theory algorithm. Results were used in conjunction with network scoring and visualization software to analyze correlated SNP across 39 fatty acid phenotypes to identify SNP of significance. Significant pathways implicated in fatty acid metabolism through GO term enrichment analysis included homeostasis of number of cells, homeostatic process, coenzyme/cofactor activity, and immunoglobulin. These results suggest different metabolic pathways regulate the development of different types of lipids found in bovine muscle tissues. Network analysis using partial correlations and annotation of significant SNPs can yield information about the genetic architecture of complex traits. PMID- 27379165 TI - Adaptive Shape Kernel-Based Mean Shift Tracker in Robot Vision System. AB - This paper proposes an adaptive shape kernel-based mean shift tracker using a single static camera for the robot vision system. The question that we address in this paper is how to construct such a kernel shape that is adaptive to the object shape. We perform nonlinear manifold learning technique to obtain the low dimensional shape space which is trained by training data with the same view as the tracking video. The proposed kernel searches the shape in the low-dimensional shape space obtained by nonlinear manifold learning technique and constructs the adaptive kernel shape in the high-dimensional shape space. It can improve mean shift tracker performance to track object position and object contour and avoid the background clutter. In the experimental part, we take the walking human as example to validate that our method is accurate and robust to track human position and describe human contour. PMID- 27379166 TI - Small Intestinal Bacterial Overgrowth in Patients with Irritable Bowel Syndrome: Clinical Characteristics, Psychological Factors, and Peripheral Cytokines. AB - Small intestinal bacterial overgrowth (SIBO) has been implicated in the pathogenesis of irritable bowel syndrome (IBS). Psychosocial factors and low grade colonic mucosal immune activation have been suggested to play important roles in the pathophysiology of IBS. In total, 94 patients with IBS and 13 healthy volunteers underwent a 10 g lactulose hydrogen breath test (HBT) with concurrent (99m)Tc scintigraphy. All participants also completed a face-to-face questionnaire survey, including the Hospital Anxiety and Depression Scale, Life Event Stress (LES), and general information. Serum tumour necrosis factor-alpha, interleukin- (IL-) 6, IL-8, and IL-10 levels were measured. The 89 enrolled patients with IBS and 13 healthy controls had no differences in baseline characteristics. The prevalence of SIBO in patients with IBS was higher than that in healthy controls (39% versus 8%, resp.; p = 0.026). Patients with IBS had higher anxiety, depression, and LES scores, but anxiety, depression, and LES scores were similar between the SIBO-positive and SIBO-negative groups. Psychological disorders were not associated with SIBO in patients with IBS. The serum IL-10 level was significantly lower in SIBO-positive than SIBO-negative patients with IBS. PMID- 27379167 TI - Effects of Hypoxia and Chitosan on Equine Umbilical Cord-Derived Mesenchymal Stem Cells. AB - Chitosan opens new perspectives in regenerative medicine as it enhances the properties of mesenchymal stem cells (MSCs) through formation of spheroids. Hypoxia has also been proposed to enhance stemness and survival of MSCs after in vivo implantation. These characteristics are relevant to the development of an off-the-shelf source of allogenic cells for regenerative therapy of tendinopathies. Umbilical cord-derived MSCs (UCM-MSCs) offer an abundant source of immature and immunoprivileged stem cells. In this study, equine UCM-MSCs (eqUCM-MSCs) conditioned for 3 and 7 days on chitosan films at 5% oxygen were compared to eqUCM-MSCs under standard conditions. Equine UCM-MSCs formed spheroids on chitosan but yielded 72% less DNA than standard eqUCM-MSCs. Expression of Sox2, Oct4, and Nanog was 4 to 10 times greater in conditioned cells at day 7. Fluorescence-labeled cells cultured for 7 days under standard conditions or on chitosan films under hypoxia were compared in a bilateral patellar tendon defect model in rats. Fluorescence was present in all treated tendons, but the modulus of elasticity under tension was greater in tendons treated with conditioned cells. Chitosan and hypoxia affected cell yield but improved the stemness of eqUCM-MSCs and their contribution to the healing of tissues. Given the abundance of allogenic cells, these properties are highly relevant to clinical applications and outweigh the negative impact on cell proliferation. PMID- 27379168 TI - Growth and descent of the testes in infants with hypogonadotropic hypogonadism receiving subcutaneous gonadotropin infusion. AB - BACKGROUND: One third of infants with congenital hypogonadotropic hypogonadism (CHH) are said to have micropenis and/or bilateral or unilateral cryptorchidism leading many of them to orchiopexy. Our previous study in two patients suggests that prolonged subcutaneous infusion of large doses of gonadotropins might normalize testicular function and growth. CASE PRESENTATION: To confirm the effects of early and prolonged subcutaneous infusion of large doses of gonadotropins on growth and descent of the testes. Eight boys with CHH, aged 0.25 11 months. Testes were non-palpable in 5 or in high scrotal position in 3. CHH was isolated in 5 infants and part of a syndrome of combined pituitary hormonal deficits in the 3 others. In response to gonadotropin infusion, mean levels of testicular hormones were normalized. Complete testis descent occurred in 6 patients. Partial descent occurred in 2. Testes re-ascended in 1 patient. Testes and penis gained normal dimensions in all cases. CONCLUSION: Subcutaneous gonadotropin infusion seems able to induce testis descent in a large proportion of infants with CHH. If confirmed, this may allow patients to avoid testes surgery but studies in larger series are needed to evaluate the benefits of this treatment versus traditional orchiopexy. PMID- 27379169 TI - Identification of Raoultella terrigena as a Rare Causative Agent of Subungual Abscess Based on 16S rRNA and Housekeeping Gene Sequencing. AB - A 63-year-old-man was admitted to our hospital with severe subungual abscess. Bacteria were isolated from pus samples, and an inconsistent identification was shown by VITEK 2 system and MALDI-TOF mass spectrometry as Raoultella planticola and Raoultella terrigena, respectively. Molecular identification by 16S rRNA sequencing suggested that the isolate is R. terrigena, and this was further demonstrated by sequencing three housekeeping genes (rpoB, gyrA, and parC) with phylogenetic analysis. To our knowledge, this is the first report of subungual abscess caused by R. terrigena, a rare case of human infection due to soil bacterium. Our study highlights the technique importance on this pathogen identification. PMID- 27379170 TI - Regional Influences on Chinese Medicine Education: Comparing Australia and Hong Kong. AB - High quality education programs are essential for preparing the next generation of Chinese medicine (CM) practitioners. Currently, training in CM occurs within differing health and education policy contexts. There has been little analysis of the factors influencing the form and status of CM education in different regions. Such a task is important for understanding how CM is evolving internationally and predicting future workforce characteristics. This paper compares the status of CM education in Australia and Hong Kong across a range of dimensions: historical and current positions in the national higher education system, regulatory context and relationship to the health system, and public and professional legitimacy. The analysis highlights the different ways in which CM education is developing in these settings, with Hong Kong providing somewhat greater access to clinical training opportunities for CM students. However, common trends and challenges shape CM education in both regions, including marginalisation from mainstream health professions, a small but established presence in universities, and an emphasis on biomedical research. Three factors stand out as significant for the evolution of CM education in Australia and Hong Kong and may have international implications: continuing biomedical dominance, increased competition between universities, and strengthened links with mainland China. PMID- 27379171 TI - Image Reconstruction Using Analysis Model Prior. AB - The analysis model has been previously exploited as an alternative to the classical sparse synthesis model for designing image reconstruction methods. Applying a suitable analysis operator on the image of interest yields a cosparse outcome which enables us to reconstruct the image from undersampled data. In this work, we introduce additional prior in the analysis context and theoretically study the uniqueness issues in terms of analysis operators in general position and the specific 2D finite difference operator. We establish bounds on the minimum measurement numbers which are lower than those in cases without using analysis model prior. Based on the idea of iterative cosupport detection (ICD), we develop a novel image reconstruction model and an effective algorithm, achieving significantly better reconstruction performance. Simulation results on synthetic and practical magnetic resonance (MR) images are also shown to illustrate our theoretical claims. PMID- 27379172 TI - Automatic Identification of Interictal Epileptiform Discharges in Secondary Generalized Epilepsy. AB - Ictal epileptiform discharges (EDs) are characteristic signal patterns of scalp electroencephalogram (EEG) or intracranial EEG (iEEG) recorded from patients with epilepsy, which assist with the diagnosis and characterization of various types of epilepsy. The EEG signal, however, is often recorded from patients with epilepsy for a long period of time, and thus detection and identification of EDs have been a burden on medical doctors. This paper proposes a new method for automatic identification of two types of EDs, repeated sharp-waves (sharps), and runs of sharp-and-slow-waves (SSWs), which helps to pinpoint epileptogenic foci in secondary generalized epilepsy such as Lennox-Gastaut syndrome (LGS). In the experiments with iEEG data acquired from a patient with LGS, our proposed method detected EDs with an accuracy of 93.76% and classified three different signal patterns with a mean classification accuracy of 87.69%, which was significantly higher than that of a conventional wavelet-based method. Our study shows that it is possible to successfully detect and discriminate sharps and SSWs from background EEG activity using our proposed method. PMID- 27379173 TI - Epigenetic origin of adaptive phenotypic variants in the human blood fluke Schistosoma mansoni. AB - BACKGROUND: Adaptive evolution is not possible without the generation of phenotypic variants. The origin of these variations has been a central topic in evolutionary biology. Up to now, it was commonly accepted that standing genetic variation is the only cause of phenotypic variants. However, epigenetic information is emerging as a complementary source of heritable phenotypic variation that contributes to evolution. The relative importance of genetics and epigenetics in generating heritable phenotypic variation is nevertheless a matter of debate. RESULTS: We used a host-parasite system to address this question. The human blood fluke Schistosoma mansoni can adapt rapidly to new intermediate snail hosts. The interaction between parasite and mollusk is characterized by a compatibility polymorphism illustrating the evolutionary dynamics in this system. The principal molecular marker for compatibility (infection success) is the expression pattern of a group of polymorphic mucins (SmPoMuc) in the parasite. We show here that chromatin structure changes as the SmPoMuc promoters are the cause for SmPoMuc transcription polymorphism leading to phenotypic novelty and increase in infection success, i.e., fitness. CONCLUSION: We establish that epigenetic changes can be the major if not only cause of adaptive phenotypic variants in Schistosoma mansoni, suggesting that epimutations can provide material for adaptive evolution in the absence of genetic variation in other systems. In addition, our results indicate that epidrugs can be used to control parasite development but also parasite evolution. PMID- 27379175 TI - Sirtuins and Cancer: Role in the Epithelial-Mesenchymal Transition. AB - The human sirtuins (SIRT1-SIRT7) enzymes are a highly conserved family of NAD(+) dependent histone deacetylases, which play a critical role in the regulation of a large number of metabolic pathways involved in stress response and aging. Cancer is an age-associated disease, and sirtuins may have a considerable impact on a plethora of processes that regulate tumorigenesis. In particular, growing evidence suggests that sirtuins may modulate epithelial plasticity by inducing transcriptional reprogramming leading to epithelial-mesenchymal transition (EMT), invasion, and metastases. Though commonly regarded as EMT inducers, sirtuins may also suppress this process, and their functional properties seem to largely depend on the cellular context, stage of cancer development, tissue of origin, and microenvironment architecture. Here, we review the role of sirtuins in cancer biology with particular emphasis on their role in EMT. PMID- 27379176 TI - Immediate Remote Ischemic Postconditioning Reduces Brain Nitrotyrosine Formation in a Piglet Asphyxia Model. AB - Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention that could be administered as an alternative to cooling in cases of perinatal hypoxia-ischemia (HI). In the current study we hypothesized that RIPostC in the piglet model of birth asphyxia confers protection by reducing nitrosative stress and subsequent nitrotyrosine formation, as well as having an effect on glial immunoreactivity. Postnatal day 1 (P1) piglets underwent HI brain injury and were randomised to HI (control) or HI + RIPostC. Immunohistochemistry assessment 48 hours after HI revealed a significant decrease in brain nitrotyrosine deposits in the RIPostC-treated group (p = 0.02). This was accompanied by a significant increase in eNOS expression (p < 0.0001) and decrease in iNOS (p = 0.010), with no alteration in nNOS activity. Interestingly, RIPostC treatment was associated with a significant increase in GFAP (p = 0.002) and IBA1 (p = 0.006), markers of astroglial and microglial activity, respectively. The current study demonstrates a beneficial effect of RIPostC therapy in the preclinical piglet model of neonatal asphyxia, which appears to be mediated by modulation of nitrosative stress, despite glial activation. PMID- 27379174 TI - Current status of biomarker research in neurology. AB - Neurology is one of the typical disciplines where personalized medicine has been recently becoming an important part of clinical practice. In this article, the brief overview and a number of examples of the use of biomarkers and personalized medicine in neurology are described. The various issues in neurology are described in relation to the personalized medicine and diagnostic, prognostic as well as predictive blood and cerebrospinal fluid biomarkers. Such neurological domains discussed in this work are neuro-oncology and primary brain tumors glioblastoma and oligodendroglioma, cerebrovascular diseases focusing on stroke, neurodegenerative disorders especially Alzheimer's and Parkinson's diseases and demyelinating diseases such as multiple sclerosis. Actual state of the art and future perspectives in diagnostics and personalized treatment in diverse domains of neurology are given. PMID- 27379177 TI - Diagnostic, Prognostic, and Therapeutic Value of Circulating miRNAs in Heart Failure Patients Associated with Oxidative Stress. AB - Heart failure is a major public health problem especially in the aging population (>=65 years old), affecting nearly 5 million Americans and 15 million European people. Effective management of heart failure (HF) depends on a correct and rapid diagnosis. Presently, BNP (brain natriuretic peptide) or N-terminal pro-brain natriuretic peptide (NT-proBNP) assay is generally accepted by the international community for diagnostic evaluation and risk stratification of patients with HF. However, regardless of its widespread clinical use, BNP is still encumbered by reduced specificity. As a result, diagnosis of heart failure remains challenging. Although significant improvement happened in the clinical management of HF over the last 2 decades, traditional treatments are ultimately ineffective in many patients who progress to advanced HF. Therefore, a novel diagnostic, prognostic biomarker and new therapeutic approach are required for clinical management of HF patients. Circulating miRNAs seem to be the right choice for novel noninvasive biomarkers as well as new treatment strategies for HF. In this review, we briefly discuss the diagnostic, prognostic, and therapeutic role of circulating miRNAs in heart failure patients. We also mentioned our own technique of extraction of RNA and detection of circulating miRNAs from human plasma and oxidative stress associated miRNAs with HF. PMID- 27379178 TI - The immediate effect of multiple mechanical impulses on electromyography and pressure pain threshold of lumbar latent trigger points: an experimental study. AB - BACKGROUND: Myofascial pain is a common syndrome, which has not been studied extensively in the low back. Despite a variety of manual and instrument assisted interventions available, little work has targeted the possible effects of fast mechanical impulses on myofascial trigger points (MTrPs) on its sensitivity and electrical activity. The purpose of this experimental study was to quantify the immediate effect of one session of mechanical impulses to lumbar latent MTrPs and to normal muscle tissue with pressure pain threshold (PPT) and surface electromyography (sEMG) as outcome measures. METHODS: During the autumn of 2009, in 41 asymptomatic subjects between 17-40 years of age the lumbar musculature was searched for a latent MTrP by a trained clinician. Using 3 disposable pre-gelled electrodes bilaterally, sEMG was recorded continuously from muscle containing either latent or no MTrP. Both the trigger point group and control group received the intervention and were blinded to group allocation. The immediate effects of mechanical impulses were assessed by sEMG and PPT before and after intervention using Wilcoxon matched-pairs signed-ranks test, Mann-Whitney U test and paired t tests. RESULTS: The PPT increased significantly across both groups (p < 0.01) after intervention. The proportionate increase (14.6 %) was comparable in both MTrP and control groups. The electrical activity on the MTrP side was not significantly higher in the MTrP group compared to the contralateral side. The decrease of resting electrical activity after intervention was significant in the MTrP group on the side of the latent MTrP (P = 0.001) as well as the contralateral side (p=0.022), and not significant in the control group on either side (p=0.33 and p=0.93). CONCLUSION: In this study, the immediate effect of one session of mechanical impulses was associated with a significant increase in PPT for both groups and a significant decrease in the resting electrical activity of the lumbar muscles only in the MTrP group. It is unknown if these effects have clinical significance. PMID- 27379179 TI - Eight unique basal bodies in the multi-flagellated diplomonad Giardia lamblia. AB - Giardia lamblia is an intestinal parasitic protist that causes significant acute and chronic diarrheal disease worldwide. Giardia belongs to the diplomonads, a group of protists in the supergroup Excavata. Diplomonads are characterized by eight motile flagella organized into four bilaterally symmetric pairs. Each of the eight Giardia axonemes has a long cytoplasmic region that extends from the centrally located basal body before exiting the cell body as a membrane-bound flagellum. Each basal body is thus unique in its cytological position and its association with different cytoskeletal features, including the ventral disc, axonemes, and extra-axonemal structures. Inheritance of these unique and complex cytoskeletal elements is maintained through basal body migration, duplication, maturation, and their subsequent association with specific spindle poles during cell division. Due to the complex composition and inheritance of specific basal bodies and their associated structures, Giardia may require novel basal body associated proteins. Thus, protists such as Giardia may represent an undiscovered source of novel basal body-associated proteins. The development of new tools that make Giardia genetically tractable will enable the composition, structure, and function of the eight basal bodies to be more thoroughly explored. PMID- 27379180 TI - Fast exchange fluxes around the pyruvate node: a leaky cell model to explain the gain and loss of unlabelled and labelled metabolites in a tracer experiment. AB - BACKGROUND: Glucose and glutamine are the two dominant metabolic substrates in cancer cells. In (13)C tracer experiments, however, it is necessary to account for all significant input substrates, as some natural (unlabelled) substrate in the medium, often derived from serum, can be metabolised by cells despite not showing signs of net consumption. RESULTS: Using [U-(13)C6]-glucose tracers and measuring extracellular metabolite enrichments by GC-MS, we found that pancreatic cells HPDE and PANC-1 secrete lactate, pyruvate, TCA cycle metabolites and non essential amino acids synthesised from glucose. Focusing our investigations on pyruvate exchange in HEK293 cells, we observed that the four metabolites pools, intracellular and extracellular lactate and pyruvate, had similar (13)C enrichment trajectories. This indicated that these metabolites can mix rapidly. Using a hybrid (13)C-MFA, we followed to show that the lactate exchange flux had increased when extracellular lactate concentration was increased by 10-fold. By allowing rapid exchange fluxes around the pyruvate node, (13)C-MFA revealed that PANC-1 cells cultured in [U-(13)C6]-glucose doubled the conversion of unlabelled substrates to pyruvate when treated with TNF-alpha. CONCLUSIONS: The current work established the possibility that a cell's range of significant input substrates may be broader than anticipated. Metabolite exchange can affect intracellular enrichments. In particular, we showed that pyruvate was more strongly connected to lactate than to upstream glycolytic intermediates and that a fast lactate exchange may alter the outcome of flux analyses. Nevertheless, the leaky cell model may be an opportunity in disguise-the ability to continuously monitor metabolism using only the enrichments of extracellular metabolites. PMID- 27379181 TI - Assessment of Corneal Epithelial Thickness in Asymmetric Keratoconic Eyes and Normal Eyes Using Fourier Domain Optical Coherence Tomography. AB - Purpose. To compare the characteristics of asymmetric keratoconic eyes and normal eyes by Fourier domain optical coherence tomography (OCT) corneal mapping. Methods. Retrospective corneal and epithelial thickness OCT data for 74 patients were compared in three groups of eyes: keratoconic (n = 22) and normal fellow eyes (n = 22) in patients with asymmetric keratoconus and normal eyes (n = 104) in healthy subjects. Areas under the curve (AUC) of receiver operator characteristic (ROC) curves for each variable were compared across groups to indicate their discrimination capacity. Results. Three variables were found to differ significantly between fellow eyes and normal eyes (all p < 0.05): minimum corneal thickness, thinnest corneal point, and central corneal thickness. These variables combined showed a high discrimination power to differentiate fellow eyes from normal eyes indicated by an AUC of 0.840 (95% CI: 0.762-0.918). Conclusions. Our findings indicate that topographically normal fellow eyes in patients with very asymmetric keratoconus differ from the eyes of healthy individuals in terms of their corneal epithelial and pachymetry maps. This type of information could be useful for an early diagnosis of keratoconus in topographically normal eyes. PMID- 27379182 TI - A Pilot Study of Parent Mentors for Early Childhood Obesity. AB - Objective. To assess the feasibility of a parent mentor model of intervention for early childhood obesity using positive deviance-based methods to inform the intervention. Methods. In this pilot, randomized clinical trial, parent-child dyads (age: 2-5) with children whose body mass index (BMI) was >=95th percentile were randomized to parent mentor intervention or community health worker comparison. The child's height and weight were measured at baseline, after the six-month intervention, and six months after the intervention. Feasibility outcomes were recruitment, participation, and retention. The primary clinical outcome was BMI z-score change. Results. Sixty participants were enrolled, and forty-eight completed the six-month intervention. At baseline, the BMI z-score in the parent mentor group was 2.63 (SD = 0.65) and in the community health worker group it was 2.61 (SD = 0.89). For change in BMI z-score over time, there was no difference by randomization group at the end of the intervention: -0.02 (95% CI: 0.26, 0.22). At the end of the intervention, the BMI z-score for the parent mentor group was 2.48 (SD = 0.58) and for the community health worker group it was 2.45 (SD = 0.91), both reduced from baseline, p < 0.001. Conclusion. The model of a parent mentor clinical trial is feasible, and both randomized groups experienced small, sustained effects on adiposity in an obese, Hispanic population. PMID- 27379183 TI - The Effect of Preoperative Type 2 Diabetes and Physical Fitness on Mental Health and Health-Related Quality of Life after Roux-en-Y Gastric Bypass. AB - Objective. To investigate the predictive value of type 2 diabetes and lack of physical activity for mental health and health-related quality of life after Roux en-Y gastric bypass. Method. Forty severely obese patients undergoing Roux-en-Y gastric bypass were included in the GASMITO study. Information about physiological and psychological factors was prospectively assessed at four time points, two times prior to surgery and two times after surgery. Measures included oral and intravenous glucose tolerance tests, VO2max test, Symptoms Checklist (SCL-90), Short Form Health Survey 36 (SF-36), Body Image Questionnaire, and a questionnaire assessing sociodemographic factors and medical status. Results. Mean % excess weight loss was 65% (+/-12) at 18-month follow-up and 50% of the participants with diabetes experienced total remission. Also, significant improvements were observed with regard to physical fitness, mental distress, health-related quality of life, and weight-related body image (p < 0.05). The interaction between follow-up time and type 2 diabetes at baseline significantly predicted six of the thirteen psychological subscales (p < 0.05) and, across the follow-ups, physical fitness level made modest contributions to variations in mental symptoms and HRQOL but not weight-related body image. Conclusion. The results suggest that baseline difference in mental symptoms and physical HRQOL between diabetic and nondiabetic patients declines across follow-ups and resolves around the time of surgery. PMID- 27379185 TI - The Regional Centralization of Electronic Fetal Heart Rate Monitoring and Its Impact on Neonatal Acidemia and the Cesarean Birth Rate. AB - Objective. The improvement of the accuracy of fetal heart rate (FHR) pattern interpretation to improve perinatal outcomes remains an elusive challenge. We examined the impact of an FHR centralization system on the incidence of neonatal acidemia and cesarean births. Methods. We performed a regional, population-based, before-and-after study of 9,139 deliveries over a 3-year period. The chi-squared test was used for the statistical analysis. Results. The before-and-after study showed no difference in the rates of acidemia, cesarean births, or perinatal death in the whole population. A subgroup analysis using the 4 hospitals in which an FHR centralization system was continuously connected (compliant group) and 3 hospitals in which the FHR centralization system was connected on demand (noncompliant group) showed that the incidence acidemia was significantly decreased (from 0.47% to 0.11%) without a corresponding increase in the cesarean birth rate due to nonreassuring FHR patterns in the compliant group. Although there was no difference in the incidence of nonreassuring FHR patterns in the noncompliant group, the total cesarean birth rate was significantly higher than that in the compliant group. Conclusion. The continuous FHR centralization system, in which specialists help to interpret results and decide clinical actions, was beneficial in reducing the incidence of neonatal acidemia (pH < 7.1) without increasing the cesarean birth rate due to nonreassuring FHR patterns. PMID- 27379184 TI - Relationships between Wasting and Stunting and Their Concurrent Occurrence in Ghanaian Preschool Children. AB - Objective. The main aim of the study was to assess the magnitude of concurrent wasting and stunting among Ghanaian preschool children. Secondly, we investigated the relationship between wasting and stunting as well as factors associated with these conditions. Methods. This paper is based on reanalysis of anthropometric and other relevant data which was collected in the 2014 Ghana Demographic and Health Survey. The data set consisted of 2,720 preschool children aged 0-59 months. We conducted three-step moderated hierarchical multiple regression analyses to determine independent predictors and moderators of height-for-age Z score. Results. Nationally, the prevalence of concurrent wasting and stunting among children aged 0-59 months was low at 1.4% but it varied geographically with the Upper East Region having the highest prevalence of 3.2% (95% CI: 1.7-5.8). Children who had low weight-for-height Z-scores were at a higher risk of linear growth retardation (stunting) especially among children aged less than three years. A 1-unit increase in weight-for-height Z-score (WHZ) was associated with 0.07 standard units' increase in height-for-age Z-score (HAZ) [beta = 0.071 (95% CI: 0.03, 0.15)]. Conclusions. The study results suggest that weight-for-height relates to linear growth but this relationship is moderated by age of child. Stunting and wasting share some common risk factors. Therefore, measures to prevent wasting may positively influence linear growth. PMID- 27379186 TI - Disparities in Survival with Bystander CPR following Cardiopulmonary Arrest Based on Neighborhood Characteristics. AB - The American Heart Association reports the annual incidence of out-of-hospital cardiopulmonary arrests (OHCA) is greater than 300,000 with a survival rate of 9.5%. Bystander cardiopulmonary resuscitation (CPR) saves one life for every 30, with a 10% decrease in survival associated with every minute of delay in CPR initiation. Bystander CPR and training vary widely by region. We conducted a retrospective study of 320 persons who suffered OHCA in South Florida over 25 months. Increased survival, overall and with bystander CPR, was seen with increasing income (p = 0.05), with a stronger disparity between low- and high income neighborhoods (p = 0.01 and p = 0.03, resp.). Survival with bystander CPR was statistically greater in white- versus black-predominant neighborhoods (p = 0.04). Increased survival, overall and with bystander CPR, was seen with high- versus low-education neighborhoods (p = 0.03). Neighborhoods with more high school age persons displayed the lowest survival. We discovered a significant disparity in OHCA survival within neighborhoods of low-income, black predominance, and low-education. Reduced survival was seen in neighborhoods with larger populations of high school students. This group is a potential target for training, and instruction can conceivably change survival outcomes in these neighborhoods, closing the gap, thus improving survival for all. PMID- 27379188 TI - Focal Hyperhidrosis Associated with Recurrent Urinary Tract Infections. AB - Hyperhidrosis affects almost 3% of the population and is characterized by sweating that occurs in excess of that needed for normal thermoregulation. It can occur as a primary disease or secondary to underlying clinical conditions. Hyperhidrosis can stem from neurogenic sympathetic over activity involving normal eccrine glands. We report the interesting case of a 75-year-old male patient with a 6-month history of new onset secondary focal hyperhidrosis of buttocks, pelvis, and upper thighs. Each time his symptoms worsened he was found to have culture positive urine samples for Escherichia coli (E. coli). He underwent urological investigation and was found to have urethral strictures and cystitis. The hyperhidrosis improved each time his urinary tract infection (UTI) was treated with antibiotics and continued to remain stable with a course of prophylactic trimethoprim. We hypothesize that the patient's urethral strictures led to inhibition in voiding which in turn increased the susceptibility to UTIs. Accumulation of urine and increased bladder pressure in turn raised sympathetic nerve discharge leading to excessive sweating. We recommend that a urine dip form part of the routine assessment of patients presenting with new onset focal hyperhidrosis of pelvis, buttocks, and upper thighs. Timely urological referral should be made for all male patients with recurrent UTI. To the authors' knowledge, there have been no other reports of UTI-associated focal hyperhidrosis. PMID- 27379189 TI - Aspergillus fumigatus Endophthalmitis with Necrotizing Scleritis following Pars Plana Vitrectomy. AB - We present a case of Aspergillus fumigatus endophthalmitis complicated by necrotizing scleritis in a 68-year-old man with diet-controlled diabetes, after retinal detachment repair. He was initially treated with systemic steroids for surgically induced necrotizing scleritis following routine pars plana vitrectomy. An additional diagnosis of endophthalmitis was made when the patient developed a hypopyon. Repeat vitreous culture isolated Aspergillus fumigatus. Symptoms improved following antifungal treatment leaving the patient with scleromalacia and an advanced postoperative cataract. Fungal scleritis and endophthalmitis are rare complications of intraocular surgery with sight-threatening consequences, and, as this case demonstrates, may even occur concomitantly. The overlapping features of both conditions can make differentiating one from the other difficult. A fungal aetiology should be considered in cases of postoperative scleritis and endophthalmitis that are protracted and refractory to standard therapy. Even in cases of early diagnosis and treatment, visual outcomes in Aspergillus endophthalmitis and scleritis are variable and often disappointing, not infrequently necessitating enucleation of a painful blind eye. PMID- 27379187 TI - KV1 and KV3 Potassium Channels Identified at Presynaptic Terminals of the Corticostriatal Synapses in Rat. AB - In the last years it has been increasingly clear that KV-channel activity modulates neurotransmitter release. The subcellular localization and composition of potassium channels are crucial to understanding its influence on neurotransmitter release. To investigate the role of KV in corticostriatal synapses modulation, we combined extracellular recording of population-spike and pharmacological blockage with specific and nonspecific blockers to identify several families of KV channels. We induced paired-pulse facilitation (PPF) and studied the changes in paired-pulse ratio (PPR) before and after the addition of specific KV blockers to determine whether particular KV subtypes were located pre or postsynaptically. Initially, the presence of KV channels was tested by exposing brain slices to tetraethylammonium or 4-aminopyridine; in both cases we observed a decrease in PPR that was dose dependent. Further experiments with tityustoxin, margatoxin, hongotoxin, agitoxin, dendrotoxin, and BDS-I toxins all rendered a reduction in PPR. In contrast heteropodatoxin and phrixotoxin had no effect. Our results reveal that corticostriatal presynaptic KV channels have a complex stoichiometry, including heterologous combinations KV1.1, KV1.2, KV1.3, and KV1.6 isoforms, as well as KV3.4, but not KV4 channels. The variety of KV channels offers a wide spectrum of possibilities to regulate neurotransmitter release, providing fine-tuning mechanisms to modulate synaptic strength. PMID- 27379190 TI - Giant Primary Schwannoma of the Left Nasal Cavity and Ethmoid Sinus. AB - A unilateral tumour in the nasal cavity or paranasal sinuses is commonly caused by polyps, cysts, and mucoceles, as well as invasive tumours such as papillomas and squamous cell carcinomas. Schwannomas, in contrast, are rare lesions in this area (Minhas et al., 2013). We present a case of a 52-year-old female who presented with a 4-year progressive history of mucous hypersecretion, nasal obstruction, pain, and fullness. Imaging of the paranasal sinuses showed complete opacification of the entire left nasal cavity and sinuses by a tumour causing subsequent obstruction of the frontal and maxillary sinuses. The tumour was completely excised endoscopically. Histopathology was consistent with that of a schwannoma. PMID- 27379191 TI - Diplopia, Convergent Strabismus, and Eye Abduction Palsy in a 12-Year-Old Boy with Autoimmune Thyroiditis. AB - Pseudotumor cerebri (PTC) is defined by clinical criteria of increased intracranial pressure, elevated intracranial pressure with normal cerebrospinal fluid (CSF) composition, and exclusion of other causes such tumors, vascular abnormalities, or infections. The association of PTC with levothyroxine (LT4) has been reported. A 12-year-old boy has been followed up for autoimmune thyroiditis under LT4. Family history was irrelevant for endocrine or autoimmune diseases. A TSH level of 4.43 MUUI/mL (0.39-3.10) motivated a LT4 adjustment from 75 to 88 MUg/day. Five weeks later, he developed horizontal diplopia, convergent strabismus with left eye abduction palsy, and papilledema. Laboratorial evaluation revealed elevated free thyroxine level (1.05 ng/dL [0.65-1.01]) and low TSH, without other alterations. Lumbar puncture was performed and CSF opening pressure was 24 cm H2O with normal composition. Blood and CSF cultures were sterile. Brain MRI was normal. LT4 was temporarily discontinued and progressive improvement was observed, with a normal fundoscopy at day 10 and reversion of diplopia one month later. LT4 was restarted at lower dose and gradually titrated. The boy is currently asymptomatic. This case discloses the potential role of LT4 in inducing PTC. Despite its rarity and unclear association, PTC must be seen as a potential complication of LT4, after excluding all other intracranial hypertension causes. PMID- 27379192 TI - CT Findings of Axillary Tuberculosis Lymphadenitis: A Case Detected by Breast Cancer Screening Examination. AB - We report the first description of CT findings of axillary tuberculous lymphadenitis confirmed by the pathological specimen. The breast cancer screening examination is one of the prime methods of detection of axillary tuberculous lymphadenitis. The most common site of axillary tuberculous lymphadenitis is the deep axilla. Screening mammography often fails to cover the whole axilla. The presence on the contrast-enhanced CT of unilateral multiple circumscribed dense nodes, some of which have large and dotted calcifications, might suggest tuberculous lymphadenitis in axillary region. PMID- 27379193 TI - Torsion of the Appendix Testis in a Neonate. AB - Torsion of the appendix testis is a rare cause of scrotal swelling in the neonatal period. We present a case of torsion of the appendix testis in a one-day old male. We discuss the physical examination and radiologic studies used to make the diagnosis. Nonoperative therapy was recommended and the patient has done well. Recognition of this condition in the neonatal period can prevent surgical intervention and its associated risks. PMID- 27379194 TI - FRTL-5 Rat Thyroid Cells Release Thyroglobulin Sequestered in Exosomes: A Possible Novel Mechanism for Thyroglobulin Processing in the Thyroid. AB - Exosomes are 30-100 nm, membrane-bound vesicles containing specific cellular proteins, mRNAs, and microRNAs that take part in intercellular communication between cells. A possible role for exosomes in thyroid function has not been fully explored. In the present study, FRTL-5 rat thyroid cells were grown to confluence and received medium containing either thyroid stimulating hormone (TSH), exogenous bovine thyroglobulin (bTg), or neither additive for 24 or 48 hours followed by collection of spent medium and ultracentrifugation to isolate small vesicles. Transmission electron microscopy and Western blotting for CD9 indicated the presence of exosomes. Western blotting of exosome extract using a monoclonal anti-Tg antibody revealed a Tg-positive band at ~330 kDa (the expected size of monomeric Tg) with a higher density in TSH-treated cells compared to that in untreated cells. These results are the first to show that normal thyroid cells in culture produce exosomes containing undegraded Tg. PMID- 27379195 TI - Identification of bapA in Strains of Salmonella enterica subsp. enterica Isolated from Wild Animals Kept in Captivity in Sinaloa, Mexico. AB - bapA, previously named stm2689, encodes the BapA protein, which, along with cellulose and fimbriae, constitutes biofilms. Biofilms are communities of microorganisms that grow in a matrix of exopolysaccharides and may adhere to living tissues or inert surfaces. Biofilm formation is associated with the ability to persist in different environments, which contributes to the pathogenicity of several species. We analyzed the presence of bapA in 83 strains belonging to 17 serovars of Salmonella enterica subsp. enterica from wildlife in captivity at Culiacan's Zoo and Mazatlan's Aquarium. Each isolate amplified a product of 667 bp, which corresponds to the expected size of the bapA initiator, with no observed variation between different serovars analyzed. bapA gene was found to be highly conserved in Salmonella and can be targeted for the genus specific detection of this organism from different sources. Since bapA expression improves bacterial proliferation outside of the host and facilitates resistance to disinfectants and desiccation, the survival of Salmonella in natural habitats may be favored. Thus, the risk of bacterial contamination from these animals is increased. PMID- 27379196 TI - The Association between Birth Weight and Gestational Age and Asthma in 6-7- and 13-14-Year-Old Children. AB - Background. Previous studies that assessed the role of birth weight and gestational age in the risk of asthma have been conflicting. Objectives. To examine the association between birth weight and gestational age and symptoms of asthma. Patients and Methods. Subjects were 6656 school children of ages 6-7 and 13-14 years from urban districts of Mazandaran, Iran. ISAAC questionnaires were used. Results. There was an increased risk of "wheeze ever" in both age groups with birth weight under 2.5 kg and in all subgroups of low birth weight (LBW). Birth weight more than 3.5 kg was associated with lower risk of "severe asthma" in age group 6-7 years. With respect to gestational age, higher risks of "wheeze ever," "asthma ever," and "night cough in the past 12 months" were found in age group 13-14 years born before 37 weeks and the risk of "severe asthma" was higher in younger group (6-7 years). A lower risk of "asthma ever" was also found in 6-7 year-old children and 13-14-year-old girls who were born after 40 weeks. Conclusions. This study showed that there is a direct relation between "wheeze ever" and LBW and an inverse relation between risk of "severe asthma" and birth weight more than 3.5 kg. PMID- 27379198 TI - Static Balance in Patients with Vestibular Impairments: A Preliminary Study. AB - Aims. Vestibular system is indicated as one of the most important sensors responsible for static and dynamic postural control. In this study, we evaluated static balance in patients with unilateral vestibular impairments. Materials and Methods. We compared static balance control using Kistler force plate platform between 10 patients with unilateral vestibular impairments and 20 normal counterparts in the same sex ratio and age limits (50 +/- 7). We evaluated excursion and velocity of center of pressure (COP) and path length in anteroposterior (AP) and mediolateral (ML) planes with eyes open and with eyes closed. Results. There was no significant difference between COP excursions in ML and AP planes between both groups with eyes open and eyes closed (p value > 0.05). In contrast, the difference between velocity and path length of COP in the mentioned planes was significant between both groups with eyes open and eyes closed (p value < 0.05). Conclusions. The present study showed the static instability and balance of patients with vestibular impairments indicated by the abnormal characteristics of body balance. PMID- 27379199 TI - Frequent Episodes of Detectable Viremia in HIV Treatment-Experienced Children is Associated with a Decline in CD4+ T-cells Over Time. AB - BACKGROUND: The clinical consequences of the magnitude and the duration of detectable viremia in HIV-infected children have not been well characterized. We examined the predictors and immunologic consequences over time of frequent episodes of detectable viremia in HIV-infected children followed at Yale-New Haven Hospital. METHODS: We analyzed the CD4+ T-cell and HIV viral load over a 19 year period (1996 to 2013) of 104 HIV-infected children enrolled in the Yale Prospective Longitudinal Pediatric HIV Cohort. Both CD4+ T-lymphocytes and HIV viral load were measured at clinic visits every 3 to 4 months. Longitudinal data analyses using polynomial random coefficients models were conducted to examine overtime changes in CD4+ T-cell counts by frequency of episodes of detectable viremia. Moreover, regression analyses using logistic regression models were used to assess the predictors of frequent episodes of detectable viremia. RESULTS: One hundred and four (104) HIV-infected children with more than one HIV viral load measurement between 1996 and November 2013 were included in the analysis. Over 80% (N=86) of the children had detectable viral load (HIV RNA viral load >=50 copies/ml) during more than 50% of their clinic visits. Children with infrequent episodes of detectable viremia had significantly higher CD4+ T-cell counts overtime compared to those with frequent episodes of detectable viremia (P<0.0001). CONCLUSIONS: Both frequency and magnitude of episodes of detectable viremia had effect on CD4+ T-cells. Strict adherence to a treatment goal of undetectable HIV viremia in children is likely to be beneficial. PMID- 27379197 TI - Advances in the Use of Stem Cells in Veterinary Medicine: From Basic Research to Clinical Practice. AB - Today, several veterinary diseases may be treated with the administration of stem cells. This is possible because these cells present a high therapeutic potential and may be injected as autologous or allogenic, freshly isolated, or previously cultured. The literature supports that the process is safe and brings considerable benefits to animal health. Knowledge about how adult stem cells modulate the molecular signals to activate cell homing has also been increasingly determined, evidencing the mechanisms which enable cells to repair and regenerate injured tissues. Preclinical studies were designed for many animal models and they have contributed to the translation to the human clinic. This review shows the most commonly used stem cell types, with emphasis on mesenchymal stem cells and their mechanistic potential to repair, as well as the experimental protocols, studied diseases, and species with the highest amount of studies and applications. The relationship between stem cell protocols utilized on clinics, molecular mechanisms, and the physiological responses may offer subsidies to new studies and therefore improve the therapeutic outcome for both humans and animals. PMID- 27379201 TI - Comparison of Individual Radiosensitivity to gamma-Rays and Carbon Ions. AB - Carbon ions are an up-and-coming ion species, currently being used in charged particle radiotherapy. As it is well established that there are considerable interindividual differences in radiosensitivity in the general population that can significantly influence clinical outcomes of radiotherapy, we evaluate the degree of these differences in the context of carbon ion therapy compared with conventional radiotherapy. In this study, we evaluate individual radiosensitivity following exposure to carbon-13 ions or gamma-rays in peripheral blood lymphocytes of healthy individuals based on the frequency of ionizing radiation (IR)-induced DNA double strand breaks (DSBs) that was either misrepaired or left unrepaired to form chromosomal aberrations (CAs) (simply referred to here as DSBs for brevity). Levels of DSBs were estimated from the scoring of CAs visualized with telomere/centromere-fluorescence in situ hybridization (TC-FISH). We examine radiosensitivity at the dose of 2 Gy, a routinely administered dose during fractionated radiotherapy, and we determined that a wide range of DSBs were induced by the given dose among healthy individuals, with highly radiosensitive individuals harboring more IR-induced breaks in the genome than radioresistant individuals following exposure to the same dose. Furthermore, we determined the relative effectiveness of carbon irradiation in comparison to gamma-irradiation in the induction of DSBs at each studied dose (isodose effect), a quality we term "relative dose effect" (RDE). This ratio is advantageous, as it allows for simple comparison of dose-response curves. At 2 Gy, carbon irradiation was three times more effective in inducing DSBs compared with gamma-irradiation (RDE of 3); these results were confirmed using a second cytogenetic technique, multicolor-FISH. We also analyze radiosensitivity at other doses (0.2-15 Gy), to represent hypo- and hyperfractionation doses and determined that RDE is dose dependent: high ratios at low doses, and approaching 1 at high doses. These results could have clinical implications as IR-induced DNA damage and the ensuing CAs and genomic instability can have significant cellular consequences that could potentially have profound implications for long-term human health after IR exposure, such as the emergence of secondary cancers and other pathobiological conditions after radiotherapy. PMID- 27379200 TI - (13)C MRS and LC-MS Flux Analysis of Tumor Intermediary Metabolism. AB - We present the first validated metabolic network model for analysis of flux through key pathways of tumor intermediary metabolism, including glycolysis, the oxidative and non-oxidative arms of the pentose pyrophosphate shunt, the TCA cycle as well as its anaplerotic pathways, pyruvate-malate shuttling, glutaminolysis, and fatty acid biosynthesis and oxidation. The model that is called Bonded Cumomer Analysis for application to (13)C magnetic resonance spectroscopy ((13)C MRS) data and Fragmented Cumomer Analysis for mass spectrometric data is a refined and efficient form of isotopomer analysis that can readily be expanded to incorporate glycogen, phospholipid, and other pathways thereby encompassing all the key pathways of tumor intermediary metabolism. Validation was achieved by demonstrating agreement of experimental measurements of the metabolic rates of oxygen consumption, glucose consumption, lactate production, and glutamate pool size with independent measurements of these parameters in cultured human DB-1 melanoma cells. These cumomer models have been applied to studies of DB-1 melanoma and DLCL2 human diffuse large B-cell lymphoma cells in culture and as xenografts in nude mice at 9.4 T. The latter studies demonstrate the potential translation of these methods to in situ studies of human tumor metabolism by MRS with stable (13)C isotopically labeled substrates on instruments operating at high magnetic fields (>=7 T). The melanoma studies indicate that this tumor line obtains 51% of its ATP by mitochondrial metabolism and 49% by glycolytic metabolism under both euglycemic (5 mM glucose) and hyperglycemic conditions (26 mM glucose). While a high level of glutamine uptake is detected corresponding to ~50% of TCA cycle flux under hyperglycemic conditions, and ~100% of TCA cycle flux under euglycemic conditions, glutaminolysis flux and its contributions to ATP synthesis were very small. Studies of human lymphoma cells demonstrated that inhibition of mammalian target of rapamycin (mTOR) signaling produced changes in flux through the glycolytic, pentose shunt, and TCA cycle pathways that were evident within 8 h of treatment and increased at 24 and 48 h. Lactate was demonstrated to be a suitable biomarker of mTOR inhibition that could readily be monitored by (1)H MRS and perhaps also by FDG-PET and hyperpolarized (13)C MRS methods. PMID- 27379202 TI - Radiation-Induced Reprogramming of Pre-Senescent Mammary Epithelial Cells Enriches Putative CD44(+)/CD24(-/low) Stem Cell Phenotype. AB - The enrichment of putative CD44(+)/CD24(-/low) breast stem cell populations following exposure to ionizing radiation (IR) has been ascribed to their inherent radioresistance and an elevated frequency of symmetric division during repopulation. However, recent studies demonstrating radiation-induced phenotypic reprogramming (the transition of non-CD44(+)/CD24(-/low) cells into the CD44(+)/CD24(-/low) phenotype) as a potential mechanism of CD44(+)/CD24(-/low) cell enrichment have raised the question of whether a higher survival and increased self-renewal of existing CD44(+)/CD24(-/low) cells or induced reprogramming is an additional mode of enrichment. To investigate this question, we combined a cellular automata model with in vitro experimental data using both MCF-10A non-tumorigenic human mammary epithelial cells and MCF-7 breast cancer cells, with the goal of identifying the mechanistic basis of CD44(+)/CD24(-/low) stem cell enrichment in the context of radiation-induced cellular senescence. Quantitative modeling revealed that incomplete phenotypic reprogramming of pre senescent non-stem cells (reprogramming whereby the CD44(+)/CD24(-/low) phenotype is conveyed, along with the short-term proliferation capacity of the original cell) could be an additional mode of enriching the CD44(+)/CD24(-/low) subpopulation. Furthermore, stem cell enrichment in MCF-7 cells occurs both at lower doses and earlier time points, and has longer persistence, than that observed in MCF-10A cells, suggesting that phenotypic plasticity appears to be less regulated in breast cancer cells. Taken together, these results suggest that reprogramming of pre-senescent non-stem cells may play a significant role in both cancer and non-tumorigenic mammary epithelial populations following exposure to IR, a finding with important implications for both radiation therapy and radiation carcinogenesis. PMID- 27379204 TI - Rationally Repurposing Ruxolitinib (Jakafi ((r))) as a Solid Tumor Therapeutic. AB - We determined whether the approved myelofibrosis drug ruxolitinib (Jakafi((r))), an inhibitor of Janus kinases 1/2 (JAK1 and JAK2), could be repurposed as an anti cancer agent for solid tumors. Ruxolitinib synergistically interacted with dual ERBB1/2/4 inhibitors to kill breast as well as lung, ovarian and brain cancer cells. Knock down of JAK1/2 or of ERBB1/2/3/4 recapitulated on-target drug effects. The combination of (ruxolitinib + ERBB1/2/4 inhibitor) rapidly inactivated AKT, mTORC1, mTORC2, STAT3, and STAT5, and activated eIF2alpha. In parallel, the drug combination reduced expression of MCL-1, BCL-XL, HSP90, HSP70, and GRP78, and increased expression of Beclin1. Activated forms of STAT3, AKT, or mTOR prevented the drug-induced decline in BCL-XL, MCL-1, HSP90, and HSP70 levels. Over-expression of chaperones maintained AKT/mTOR activity in the presence of drugs and protected tumor cells from the drug combination. Expression of dominant negative eIF2alpha S51A prevented the increase in Beclin1 expression and protected tumor cells from the drug combination. Loss of mTOR activity was associated with increased ATG13 S318 phosphorylation and with autophagosome formation. Autophagosomes initially co-localized with mitochondria and subsequently with lysosomes. Knock down of Beclin1 suppressed: drug-induced mitophagy; the activation of the toxic BH3 domain proteins BAX and BAK; and tumor cell killing. Knock down of apoptosis-inducing factor (AIF) protected tumor cells from the drug combination, whereas blockade of caspase 9 signaling did not. The drug combination released AIF into the cytosol and increased nuclear AIF: eIF3A co-localization. A 4-day transient exposure of orthotopic tumors to (ruxolitinib + afatinib) profoundly reduced mammary tumor growth over the following 35 days. Re-grown tumors exhibited high levels of BAD S112 phosphorylation and activation of ERK1/2 and NFkappaB. Our data demonstrate that mitophagy is an essential component of (ruxolitinib + ERBB inhibitor) lethality and that this drug combination should be explored in a phase I trial in solid tumor patients. PMID- 27379203 TI - Modern Radiotherapy Concepts and the Impact of Radiation on Immune Activation. AB - Even though there is extensive research carried out in radiation oncology, most of the clinical studies focus on the effects of radiation on the local tumor tissue and deal with normal tissue side effects. The influence of dose fractionation and timing particularly with regard to immune activation is not satisfactorily investigated so far. This review, therefore, summarizes current knowledge on concepts of modern radiotherapy (RT) and evaluates the potential of RT for immune activation. Focus is set on radiation-induced forms of tumor cell death and consecutively the immunogenicity of the tumor cells. The so-called non targeted, abscopal effects can contribute to anti-tumor responses in a specific and systemic manner and possess the ability to target relapsing tumor cells as well as metastases. The impact of distinct RT concepts on immune activation is outlined and pre-clinical evidence and clinical observations on RT-induced immunity will be discussed. Knowledge on the radiosensitivity of immune cells as well as clinical evidence for enhanced immunity after RT will be considered. While stereotactic ablative body radiotherapy seem to have a beneficial outcome over classical RT fractionation in pre-clinical animal models, in vitro model systems suggest an advantage for classical fractionated RT for immune activation. Furthermore, the optimal approach may differ based on the tumor site and/or genetic signature. These facts highlight that clinical trials are urgently needed to identify whether high-dose RT is superior to induce anti-tumor immune responses compared to classical fractionated RT and in particular how the outcome is when RT is combined with immunotherapy in selected tumor entities. PMID- 27379205 TI - Pretransplant Locoregional Therapy for Hepatocellular Carcinoma: Evaluation of Explant Pathology and Overall Survival. AB - BACKGROUND AND OBJECTIVES: Liver transplant is an important treatment option for patients with hepatocellular carcinoma (HCC) within Milan criteria. We sought to determine the rate of complete tumor necrosis after bridging therapy. METHODS: The medical records of all 178 patients undergoing liver transplantation between January 1, 2008 and July 31, 2015 were reviewed. Response to therapy by imaging was based on mRECIST criteria (1). RESULTS: Sixty-three (35%) patients had HCC. Forty-three (68%) were treated with at least one bridging therapy and 14 (22%) were diagnosed incidentally. Eighteen (42%) underwent TACE and 25 (58%) underwent ablation. Twenty (80%) patients who underwent ablation and nine (60%) who underwent TACE had complete response based on imaging. Viable tumor was identified in explant pathology in 32 patients (74%). The presence or absence of viable tumor was not associated with overall survival. CONCLUSION: Rates of viable tumor based on pathologic analysis in the hepatic explant were high after bridging therapy, but not associated with worse outcome. We conclude that serial bridging to achieve complete pathologic tumor response is not needed prior to transplant for HCC, and presence of complete response by imaging is adequate. Further studies are needed to determine if cancer cells that appear viable are alive. PMID- 27379206 TI - Hypoxia on the Expression of Hepatoma Upregulated Protein in Prostate Cancer Cells. AB - Hepatoma upregulated protein (HURP) is a multifunctional protein with clinical promise. This protein has been demonstrated to be a predictive marker for the outcome in high-risk prostate cancer (PCa) patients, besides being a resistance factor in PCa. Although changes in oxygen tension (pO2) are associated with PCa aggressiveness, the role of hypoxia in the regulation of tumor progression genes such as HURP has not yet been described. We hypothesized that pO2 alteration is involved in the regulation of HURP expression in PCa cells. In the present study, PCa cells were incubated at 2% O2 (hypoxia) and 20% O2 (normoxia) conditions. Hypoxia reduced cell growth rate of PCa cells, when compared to the growth rate of cells cultured under normoxia (p < 0.05). The decrease in cell viability was accompanied by fivefold (p < 0.05) elevated rate of vascular endothelial growth factor (VEGF) release. The expression of VEGF and the hypoxia-inducible metabolic enzyme carbonic anhydrase 9 were elevated maximally nearly 61-fold and 200-fold, respectively (p < 0.05). Noted in two cell lines (LNCaP and C4-2B) and independent of the oxygen levels, HURP expression assessed at both mRNA and protein levels was reduced. However, the decrease was more pronounced in cells cultured under hypoxia (p < 0.05). Interestingly, the analysis of patients' specimens by Western blot revealed a marked increase of HURP protein (fivefold), when compared to control (cystoprostatectomy) tissue (p < 0.05). Immunohistochemistry analysis showed an increase in the immunostaining intensity of HURP and the hypoxia-sensitive molecules, hypoxia-inducible factor 1-alpha (HIF-1alpha), VEGF, and heat-shock protein 60 (HSP60) in association with tumor grade. The data also suggested a redistribution of subcellular localization for HURP and HIF-1alpha from the nucleus to the cytoplasmic compartment in relation to increasing tumor grade. Analysis of HURP Promoter for HIF-1-binding sites revealed presence of four putative HIF binding sites on the promoter of DLGAP5/HURP gene in the non-translated region upstream from the start codon, suggesting association between HIF-1alpha and the regulation of HURP protein. Taken together, our findings suggest a modulatory role of hypoxia on the expression of HURP. Additionally our results provide basis for utilization of tumor-associated molecules as predictors of aggressive PCa. PMID- 27379207 TI - Overexpression of Specific CD44 Isoforms Is Associated with Aggressive Cell Features in Acquired Endocrine Resistance. AB - While endocrine therapy is the mainstay of ER+ breast cancer, the clinical effectiveness of these agents is limited by the phenomenon of acquired resistance that is associated with disease relapse and poor prognosis. Our previous studies revealed that acquired resistance is accompanied by a gain in cellular invasion and migration and also that CD44 family proteins are overexpressed in the resistant phenotype. Given the association of CD44 with tumor progression, we hypothesized that its overexpression may act to promote the aggressive behavior of endocrine-resistant breast cancers. Here, we have investigated further the role of two specific CD44 isoforms, CD44v3 and CD44v6, in the endocrine-resistant phenotype. Our data revealed that overexpression of CD44v6, but not CD44v3, in endocrine-sensitive MCF-7 cells resulted in a gain in EGFR signaling, enhanced their endogenous invasive capacity, and attenuated their response to endocrine treatment. Suppression of CD44v6 in endocrine-resistant cell models was associated with a reduction in their invasive capacity. Our data suggest that upregulation of CD44v6 in acquired resistant breast cancer may contribute to a gain in the aggressive phenotype of these cells and loss of endocrine response through transactivation of the EGFR pathway. Future therapeutic targeting of CD44v6 may prove to be an effective strategy alongside EGFR-targeted agents in delaying/preventing acquired resistance in breast cancer. PMID- 27379208 TI - Tissue Microstructure Is Linked to MRI Parameters and Metabolite Levels in Prostate Cancer. AB - INTRODUCTION: Magnetic resonance imaging (MRI) can portray spatial variations in tumor heterogeneity, architecture, and its microenvironment in a non-destructive way. The objective of this study was to assess the relationship between MRI parameters measured on patients in vivo, individual metabolites measured in prostatectomy tissue ex vivo, and quantitative histopathology. MATERIALS AND METHODS: Fresh frozen tissue samples (n = 53 from 15 patients) were extracted from transversal prostate slices and linked to in vivo MR images, allowing spatially matching of ex vivo measured metabolites with in vivo MR parameters. Color-based segmentation of cryosections of each tissue sample was used to identify luminal space, stroma, and nuclei. RESULTS: Cancer samples have significantly lower area percentage of lumen and higher area percentage of nuclei than non-cancer samples (p <= 0.001). Apparent diffusion coefficient is significantly correlated with percentage area of lumen (rho = 0.6, p < 0.001) and percentage area of nuclei (rho = -0.35, p = 0.01). There is a positive correlation (rho = 0.31, p = 0.053) between citrate and percentage area of lumen. Choline is negatively correlated with lumen (rho = -0.38, p = 0.02) and positively correlated with percentage area of nuclei (rho = 0.38, p = 0.02). CONCLUSION: Microstructures that are observed by histopathology are linked to MR characteristics and metabolite levels observed in prostate cancer. PMID- 27379209 TI - Export of microRNAs: A Bridge between Breast Carcinoma and Their Neighboring Cells. AB - Breast cancer is a leading type of cancer among women in India as well as worldwide. According to the WHO 2015 report, it has been anticipated that there would be a twofold rise in the death due to breast cancer among women. The heterogeneous property of breast carcinoma has been suggested to be linked with dedicated set of communication and signaling pathway with their surroundings, which culminate into progression and development of the cancer. Among the plethora of communication tools in the hand of breast carcinoma cells is the recently appreciated exocytosis of the tightly packed short non-coding RNA molecules, predominantly the microRNAs (miRNAs). Recent studies suggest that miRNAs may work as courier messengers to participate in endocrine and paracrine signaling to facilitate information transfer between breast carcinoma and their neighboring cells. Evidence suggests that breast tumor cells communicate via packaged miRNAs in the tumor-released microvesicles, which enrich the tumor microenvironment. There is a strong view that dissecting out the mechanistic and regulatory aspects of miRNA export and role may uncover many prospects for overcoming the signaling defects and thereby controlling aberrant cell division. The detection of circulating miRNAs associated with breast carcinoma can also be used as biomarkers for early diagnosis. This review article is an attempt to provide updated knowledge on implications of short RNAs and their transport in the breast cancer pathophysiology. PMID- 27379210 TI - Appendiceal Mixed Adeno-Neuroendocrine Carcinoma: A Population-Based Study of the Surveillance, Epidemiology, and End Results Registry. AB - INTRODUCTION: Mixed adeno-neuroendocrine carcinoma (MANEC) is a rare pathological diagnosis recently defined by the World Health Organization (WHO) in 2010. Prior to the definition by the WHO, tumors with both adenocarcinoma and neuroendocrine components were given multiple pathological designations making it difficult to characterize the disease. The aim of our study is to better characterize MANEC to better understand its natural history to influence patient care and positively impact outcomes. MATERIALS AND METHODS: The surveillance, epidemiology, and end results program database was queried for all patients aged 18 years or older between 1973 and 2012 who had the diagnosis composite carcinoid (n = 249) of the appendix. Composite carcinoid tumors refer to tumors that have both adenocarcinoma and carcinoid tumor components present, consistent with that pathological diagnosis MANEC. For comparison, the database was also queried for carcinoid tumor of the appendix (n = 950), signet ring cell carcinoma of the appendix (n = 579), and goblet cell carcinoid (GCC) tumors of the appendix (n = 944). The data were retrospectively reviewed, and clinicopathological characteristics, treatment regimens, and survival data were obtained. RESULTS: The median age of diagnosis of MANEC tumors was 58 years of age. Eighty percent of patients were White, and 49% were female. Fifty-four percent of patients underwent hemicolectomy and 31% had partial/subtotal colectomy as their surgical management. Median overall survival for MANEC was 6.5 years (95% CI 4.5-9.7), which was statistically significantly shorter (p < 0.0001) in comparison to 13.8 years (95% CI 12.1-16.5) for GCC, 2.1 years (95% CI 1.8-2.3) for signet ring cell carcinoma, and 39.4 years (95% CI 37.1-NA) for carcinoid tumors. DISCUSSION: MANEC is a more aggressive clinical entity than both GCC of the appendix and carcinoid tumors of the appendix. Based on these findings, patients with MANEC tumors should undergo aggressive multidisciplinary cancer management. PMID- 27379213 TI - Conway's "Game of Life" and the Epigenetic Principle. AB - Cellular automatons and computer simulation games are widely used as heuristic devices in biology, to explore implications and consequences of specific theories. Conway's Game of Life has been widely used for this purpose. This game was designed to explore the evolution of ecological communities. We apply it to other biological processes, including symbiopoiesis. We show that Conway's organization of rules reflects the epigenetic principle, that genetic action and developmental processes are inseparable dimensions of a single biological system, analogous to the integration processes in symbiopoiesis. We look for similarities and differences between two epigenetic models, by Turing and Edelman, as they are realized in Game of Life objects. We show the value of computer simulations to experiment with and propose generalizations of broader scope with novel testable predictions. We use the game to explore issues in symbiopoiesis and evo-devo, where we explore a fractal hypothesis: that self-similarity exists at different levels (cells, organisms, ecological communities) as a result of homologous interactions of two as processes modeled in the Game of Life. PMID- 27379211 TI - Big Data Analytics for Prostate Radiotherapy. AB - Radiation therapy is a first-line treatment option for localized prostate cancer and radiation-induced normal tissue damage are often the main limiting factor for modern radiotherapy regimens. Conversely, under-dosing of target volumes in an attempt to spare adjacent healthy tissues limits the likelihood of achieving local, long-term control. Thus, the ability to generate personalized data-driven risk profiles for radiotherapy outcomes would provide valuable prognostic information to help guide both clinicians and patients alike. Big data applied to radiation oncology promises to deliver better understanding of outcomes by harvesting and integrating heterogeneous data types, including patient-specific clinical parameters, treatment-related dose-volume metrics, and biological risk factors. When taken together, such variables make up the basis for a multi dimensional space (the "RadoncSpace") in which the presented modeling techniques search in order to identify significant predictors. Herein, we review outcome modeling and big data-mining techniques for both tumor control and radiotherapy induced normal tissue effects. We apply many of the presented modeling approaches onto a cohort of hypofractionated prostate cancer patients taking into account different data types and a large heterogeneous mix of physical and biological parameters. Cross-validation techniques are also reviewed for the refinement of the proposed framework architecture and checking individual model performance. We conclude by considering advanced modeling techniques that borrow concepts from big data analytics, such as machine learning and artificial intelligence, before discussing the potential future impact of systems radiobiology approaches. PMID- 27379212 TI - Unraveling the Pathogenesis of MDS: The NLRP3 Inflammasome and Pyroptosis Drive the MDS Phenotype. AB - Myelodysplastic syndromes (MDS) are characterized by bone marrow cytological dysplasia and ineffective hematopoiesis in the setting of recurrent somatic gene mutations and chromosomal abnormalities. The underlying pathogenic mechanisms that drive a common clinical phenotype from a diverse array of genetic abnormalities have only recently begun to emerge. Accumulating evidence has highlighted the integral role of the innate immune system in upregulating inflammatory cytokines via NF-kappaB activation in the pathogenesis of MDS. Recent investigations implicate activation of the NLRP3 inflammasome in hematopoietic stem/progenitor cells as a critical convergence signal in MDS with consequent clonal expansion and pyroptotic cell death though caspase-1 maturation. Specifically, the alarmin S100A9 and/or founder gene mutations trigger pyroptosis through the generation of reactive oxygen species leading to assembly and activation of the redox-sensitive NLRP3 inflammasome and beta catenin, assuring propagation of the MDS clone. More importantly, targeted inhibition of varied steps in this pathway restore effective hematopoiesis. Together, delineation of the role of pyroptosis in the clinical phenotype of MDS patients has identified novel therapeutic strategies that offer significant promise in the treatment of MDS. PMID- 27379214 TI - Oseltamivir PK/PD Modeling and Simulation to Evaluate Treatment Strategies against Influenza-Pneumococcus Coinfection. AB - Influenza pandemics and seasonal outbreaks have shown the potential of Influenza A virus (IAV) to enhance susceptibility to a secondary infection with the bacterial pathogen Streptococcus pneumoniae (Sp). The high morbidity and mortality rate revealed the poor efficacy of antiviral drugs and vaccines to fight IAV infections. Currently, the most effective treatment for IAV is by antiviral neuraminidase inhibitors. Among them, the most frequently stockpiled is Oseltamivir which reduces viral release and transmission. However, effectiveness of Oseltamivir is compromised by the emergence of resistant IAV strains and secondary bacterial infections. To date, little attention has been given to evaluate how Oseltamivir treatment strategies alter Influenza viral infection in presence of Sp coinfection and a resistant IAV strain emergence. In this paper we investigate the efficacy of current approved Oseltamivir treatment regimens using a computational approach. Our numerical results suggest that the curative regimen (75 mg) may yield 47% of antiviral efficacy and 9% of antibacterial efficacy. An increment in dose to 150 mg (pandemic regimen) may increase the antiviral efficacy to 49% and the antibacterial efficacy to 16%. The choice to decrease the intake frequency to once per day is not recommended due to a significant reduction in both antiviral and antibacterial efficacy. We also observe that the treatment duration of 10 days may not provide a clear improvement on the antiviral and antibacterial efficacy compared to 5 days. All together, our in silico study reveals the success and pitfalls of Oseltamivir treatment strategies within IAV-Sp coinfection and calls for testing the validity in clinical trials. PMID- 27379215 TI - Physiological Roles of the Dual Phosphate Transporter Systems in Low and High Phosphate Conditions and in Capsule Maintenance of Streptococcus pneumoniae D39. AB - Unlike most bacteria, Streptococcus pneumoniae (pneumococcus) has two evolutionarily distinct ABC transporters (Pst1 and Pst2) for inorganic phosphate (Pi) uptake. The genes encoding a two-component regulator (PnpRS) are located immediately upstream of the pst1 operon. Both the pst1 and pst2 operons encode putative PhoU-family regulators (PhoU1 and PhoU2) at their ends. This study addresses why S. pneumoniae contains dual Pi uptake systems and the regulation and contribution of the Pst1 and Pst2 systems in conditions of high (mM) Pi amount and low (MUM) Pi amount. We show that in unencapsulated mutants, both pst1 and pst2 can be deleted, and Pi is taken up by a third Na(+)/Pi co-transporter, designated as NptA. In contrast, either pst1 or pst2 is unexpectedly required for the growth of capsule producing strains. We used a combination of mutational analysis, transcript level determinations by qRT-PCR and RNA-Seq, assays for cellular PnpR~P amounts by SDS-PAGE, and pulse-Pi uptake experiments to study the regulation of Pi uptake. In high Pi medium, PhoU2 serves as the master negative regulator of Pst2 transporter function and PnpR~P levels (post transcriptionally). DeltaphoU2 mutants have high PnpR~P levels and induction of the pst1 operon, poor growth, and sensitivity to antibiotics, possibly due to high Pi accumulation. In low Pi medium, Pst2 is still active, but PnpR~P amount and pst1 operon levels increase. Together, these results support a model in which pneumococcus maintains high Pi transport in high and low Pi conditions that is required for optimal capsule biosynthesis. PMID- 27379216 TI - Synthetic Cystic Fibrosis Sputum Medium Regulates Flagellar Biosynthesis through the flhF Gene in Burkholderia cenocepacia. AB - Burkholderia cenocepacia belongs to the Burkholderia cepacia complex (Bcc), a group of at least 18 distinct species that establish chronic infections in the lung of people with the genetic disease cystic fibrosis (CF). The sputum of CF patients is rich in amino acids and was previously shown to increase flagellar gene expression in B. cenocepacia. We examined flagellin expression and flagellar morphology of B. cenocepacia grown in synthetic cystic fibrosis sputum medium (SCFM) compared to minimal medium. We found that CF nutritional conditions induce increased motility and flagellin expression. Individual amino acids added at the same concentrations as found in SCFM also increased motility but not flagellin expression, suggesting a chemotactic effect of amino acids. Electron microscopy and flagella staining demonstrated that the increase in flagellin corresponds to a change in the number of flagella per cell. In minimal medium, the ratio of multiple: single: aflagellated cells was 2:3.5:4.5; while under SCFM conditions, the ratio was 7:2:1. We created a deletion mutant, DeltaflhF, to study whether this putative GTPase regulates the flagellation pattern of B. cenocepacia K56-2 during growth in CF conditions. The DeltaflhF mutant exhibited 80% aflagellated, 14% single and 6% multiple flagellated bacterial subpopulations. Moreover, the ratio of multiple to single flagella in WT and DeltaflhF was 3.5 and 0.43, respectively in CF conditions. The observed differences suggest that FlhF positively regulates flagellin expression and the flagellation pattern in B. cenocepacia K56-2 during CF nutritional conditions. PMID- 27379217 TI - Rationale for Prolonged Glucocorticoid Use in Pediatric ARDS: What the Adults Can Teach Us. AB - Based on molecular mechanisms and physiologic data, a strong association has been established between dysregulated systemic inflammation and progression of acute respiratory distress syndrome (ARDS). In ARDS patients, glucocorticoid receptor mediated downregulation of systemic inflammation is essential to restore homeostasis, decrease morbidity and improve survival and can be significantly enhanced with prolonged low-to-moderate dose glucocorticoid treatment. A large body of evidence supports a strong association between prolonged glucocorticoid treatment-induced downregulation of the inflammatory response and improvement in pulmonary and extrapulmonary physiology. The balance of the available data from eight controlled trials (n = 622) provides consistent strong level of evidence for improving patient-centered outcomes and hospital survival. The sizable increase in mechanical ventilation-free days (weighted mean difference, 6.48 days; CI 95% 2.57-10.38, p < 0.0001) and intensive care unit-free days (weighted mean difference, 7.7 days; 95% CI, 3.13-12.20, p < 0.0001) by day 28 is superior to any investigated intervention in ARDS. For treatment initiated before day 14 of ARDS, the increased in hospital survival (70 vs. 52%, OR 2.41, CI 95% 1.50 3.87, p = 0.0003) translates into a number needed to treat to save one life of 5.5. Importantly, prolonged glucocorticoid treatment is not associated with increased risk for nosocomial infections (22 vs. 27%, OR 0.61, CI 95% 0.35-1.04, p = 0.07). Treatment decisions involve a tradeoff between benefits and risks, as well as costs. This low-cost, highly effective therapy is familiar to every physician and has a low risk profile when secondary prevention measures are implemented. PMID- 27379218 TI - What Interventional Cardiologists Are Still Leaving to the Surgeons? AB - Nowadays, development of new technologies is still ongoing with the ultimate goal of maximizing treatment outcomes with less invasiveness and reduced procedural risk. This review is intended to update on when interventionalists need surgical support in common or emerging problems in congenital heart disease. PMID- 27379219 TI - BPD Following Preterm Birth: A Model for Chronic Lung Disease and a Substrate for ARDS in Childhood. AB - It has been suggested that pediatric acute respiratory distress syndrome (PARDS) may be a different entity, vis-a-vis adult acute respiratory distress syndrome (ARDS), based on its epidemiology and outcomes. A more pediatric-specific definition of PARDS to include the subgroup of patients with underlying lung (and heart) disease has been proposed. Epidemiological data suggest that up to 13% of the children with ARDS have a history of prematurity and/or underlying chronic lung disease. However, the specific contribution of bronchopulmonary dysplasia (BPD), the most common chronic lung disease in infants, to the development of PARDS is not known. BPD leads to damaged lungs with long-term consequences secondary to disordered growth and immune function. These damaged lungs could potentially act as a substrate, which given the appropriate noxious stimuli, can predispose a child to PARDS. Interestingly, similar biomarkers [KL-6, interleukin (IL)-6, IL-8, sICAM-1, angiopoietin-2, and matrix metalloproteinase-8 and -9] of pulmonary injury have been associated both with BPD and ARDS. Recognition of a unique pattern of clinical symptomatology and/or outcomes of PARDS, if present, could potentially be useful for investigating targeted therapeutic interventions. PMID- 27379220 TI - Influence of Yoga-Based Personality Development Program on Psychomotor Performance and Self-efficacy in School Children. AB - Selective attention and efficacy are important components of scholastic performance in school children. While attempts are being made to introduce new methods to improve academic performance either as part of curricular or extracurricular activities in schools, the success rates are minimal. Hence, this study assessed the effect of yoga-based intervention on psychomotor performance and self-efficacy in school children. Two hundred ten school children with ages ranging from 11 to 16 years (mean age +/- SD; 13.7 +/- 0.8 years) satisfying the inclusion and exclusion criteria were recruited for the 10-day yoga program. An equal number of age-matched participants (n = 210; mean +/- SD; 13.1 +/- 0.8 years) were selected for the control group. Participants were assessed for attention and performance at the beginning and end of 10 days using trail making task (TMT) A and B, and self-efficacy questionnaire. The yoga group showed higher self-efficacy and improved performance after 10 days of yoga intervention. The performance in TMT-A and -B of the yoga group showed a significantly higher number of attempts with a reduction in time taken to complete the task and a number of wrong attempts compared with control group. Results suggest that yoga practice enhances self-efficacy and processing speed with fine motor coordination, visual-motor integration, visual perception, planning ability, and cognitive performance. PMID- 27379221 TI - Transportation of Critically Ill Patients on Extracorporeal Membrane Oxygenation. AB - Extracorporeal membrane oxygenation (ECMO) may be a life-saving procedure for patients with severe reversible pulmonary or cardiac failure or for patients in need for a bridge to transplantation. ECMO is provided by specialized centers, but patients in need of ECMO are frequently taken care of at other centers. Conventional transports to an ECMO center can be hazardous and deaths have been described. For this reason, many ECMO centers have developed transport programs with mobile ECMO. After request, the mobile team including all necessary equipment to initiate ECMO is sent to the referring hospital, where the patient is cannulated and ECMO commenced. The patient is then transported on ECMO to the ECMO facility by road, helicopter, or fixed-wing aircraft depending on distance, weather conditions, etc. Eight publications have reported series of more than 50 transports on ECMO of which the largest included over 700. Together, these papers report on more than 1400 patient transports on ECMO. Two deaths during transport have occurred. A number of other adverse events are described, but without effect on patient outcome. Survival of patients transported on ECMO is equivalent to that of non-transported ECMO patients. It is concluded that long-, short-distance interhospital transports on ECMO can be performed safely. The staff should be experienced and highly competent in intensive care, ECMO cannulation, ECMO treatment, intensive care transport, and air transport medicine. PMID- 27379222 TI - Is Health Practitioner Regulation Keeping Pace with the Changing Practitioner and Health-Care Landscape? An Australian Perspective. AB - Health-care delivery is undergoing significant evolution and change. Task substitution has resulted in some practitioner groups expanding their scope of practice by assuming more complex clinical roles, new practitioner groups have emerged, and consumer-driven demand has changed the way the public engage with health practitioners and the way many health-care services are delivered. Using Australia as a case study, this paper explores the issue of the hesitancy to include new professions in health professions regulation schemes. Despite the significant changes in the health-care delivery landscape, policy development in this area has remained relatively static, with active resistance to extending formal registration to new practitioner groups. Ignoring the issue of new practitioner groups in regulatory schemes is unacceptable from a public health perspective and runs against the key public protection objectives of health practitioner regulation. Development of pathways for the entry of new health practitioner groups into regulatory schemes must be developed as a matter of priority. PMID- 27379223 TI - Cadmium Level, Glycemic Control, and Indices of Renal Function in Treated Type II Diabetics: Implications for Polluted Environments. AB - Cadmium (Cd) has recently emerged as a major concern not only in environmental toxicology but also in metabolic diseases such as diabetes mellitus and its complications. Conflicting data aside, these studies have not been examined in a clinical population undergoing management as well as possible modulation by the prominent metabolic antagonist of Cd such as zinc (Zn). This study examined the relationship between cadmium levels, glycemic control, and renal pathology in established type II diabetic patients with focus on populations exposed to modern environmental health hazards (MEHHs). Sixty-five participants, consisting of 45 type-2 diabetics and 20 non-diabetics were enrolled for the study, mean age 61.51 +/- 5.27 years. Glycated hemoglobin (HbA1c) was used to classify them into three sub-groups: (A) good glycemic control (44.4%), (B) fair glycemic control (24.4%), and (C) poor glycemic control (31.1%). Plasma levels of glucose, Cd, Zn, HbA1c, creatinine, urinary creatinine, microalbuminuria, and estimated glomerular filtration rate (eGFR) were determined in all participants using standard methods. Fasting plasma glucose was higher in diabetics than in non-diabetics (p = 0.000) as well as Zn level, though not significantly. Interestingly, Cd level, Cd/Zn ratio, and urinary creatinine were significantly lower in diabetics than in non-diabetics. The group with poor glycemic control (C) had significantly higher Cd level compared to the one with good glycemic control (group A). The renal function revealed that microalbuminuria and urinary albumin/creatinine ratio (UACR) was significantly higher in diabetics than in non-diabetics, while eGFR was found to be similar in both diabetics and non-diabetics. UACR inversely correlated with Cd level, while plasma creatinine level positively correlated with Cd but not significantly. Correlation between Cd and HbA1c revealed non significant inverse correlation (r = -0.007; p > 0.05), while Zn showed a significant inverse correlation with Cd (r = -0.317; p < 0.014). The lower Cd level in diabetics compared to non-diabetics probably reflects the modulating effect of Zn in treated diabetics given nutritional education in addition to their regular regime, including good sources of Zn. The renal insufficiency with increasing Cd level may suggest that the progression of renal impairment may not be responsive to the putative modulating effect of Zn. PMID- 27379224 TI - Value-Based Model: A New Perspective in Medical Decision-making. PMID- 27379225 TI - Rebuilding Earthquake Struck Nepal through Community Engagement. AB - Nepal underwent two major earthquakes during 2015 which claimed 9,000 deaths, left more than 23,000 injured, displaced about 2 million people and destroyed about 1,000 health facilities. Emerging health issues and disease outbreaks soon after the earthquakes were major priorities. However, preventive measures such as health education, health promotion and trainings embedded in community engagement remained largely unimplemented. Establishing community preparedness by delivering knowledge about the disasters, preparing contingency plans and conducting disaster drills can be promising in Nepal where geographical inaccessibility invariably impedes the on time management during disasters. The steps that could be taken in Nepal without additional resources include identifying community leaders and volunteers who could participate in health promotion initiatives, training of thus identified community volunteers, formation of community task force, devolvement of responsibilities with continual support (trainings and resources) and supervision of the community task force. PMID- 27379226 TI - Designing Evidence-Based Family Planning Programs for the Marginalized Community: An Example of Muslim Community in Nepal. AB - CONTEXT: Family planning (FP), considered as an encouraging trend for development, is thought to be positively correlated with family health and well being and negatively correlated with poverty levels. Despite being a priority goal of government and development agencies, in a heterogeneous society like Nepal, FP can be an issue that needs to be dealt with consideration for religious and cultural beliefs of different sections of society. Despite steady progress in achieving FP goals, minority populations have lagged behind the rest of the country in achieving improved family health outcomes; Muslim community being one such example. OBJECTIVES: This study aims to explore the existing situation of FP use in Muslim communities and to identify key policy-related issues affecting the access to and utilization of FP services. SETTINGS AND DESIGN: Mixed approach was used in Kapilbastu district, which accommodated the larger proportion of Muslims in Nepal. MATERIALS AND METHODS: Interview was conducted among 160 married women using semi-structured questionnaire. Focus group discussion, key informant interviews, and consultative meeting were the qualitative techniques employed in this study. Quantitative data were analyzed using descriptive and inferential statistics (Chi-square test), while qualitative data by thematic approach. RESULTS: More than half of women (56.0%) expressed their interest in FP use, while reported users were just below the quarter (24.0%). Husband approval and secrecy of their personal identity affect use of any method of contraception. Future plan for children and prior information regarding FP found to affect current use of FP, significantly. FP word itself was found to be stigmatizing, so women prefer replacing the word FP with culturally appropriate one. Furthermore, incorporating it into comprehensive package for improving women's health will definitely contribute to improve access and uptake of services. CONCLUSION: Discrepancy exists between current use and desire for use of FP among Muslim women in future. This highlights the inadequacy of implementing the current blanket policy and programs related to FP and offer ways to move forward with the national FP agenda ensuring the cultural rights and non-discrimination of women. PMID- 27379227 TI - A Journey with Elie Metchnikoff: From Innate Cell Mechanisms in Infectious Diseases to Quantum Biology. AB - Many reviews of Elie Metchnikoff's work have been published, all unanimously acknowledging the significant contributions of his cellular theory to the fields of immunology and infectious diseases. In 1883, he published a key paper describing phagocytic cells in frogs. His descriptions were not just about phagocytes involved in host defense, he also described how these specialized cells eliminated degenerating or dying cells of the host. This perspective focuses on key concepts developed by Metchnikoff by presenting relevant excerpts of his 1883 paper and matching these concepts with challenges of modern immunology. A new approach to macrophage polarization is included to introduce some creative thinking about the exciting emerging area of quantum biology. PMID- 27379228 TI - Higher Educational Attainment Associated with Optimal Antenatal Care Visits among Childbearing Women in Zambia. AB - OBJECTIVE: Attendance of at least four antenatal care (ANC) visits over the period of pregnancy has been accepted by World Health Organization to comprise the optimal and adequate standard of ANC because of its positive association with good maternal and neonatal outcomes during the prenatal period. Despite free ANC being provided, many pregnant women have been found not to meet this minimum number of ANC visits in Zambia. We investigated if educational attainment is associated with optimal ANC visits among childbearing women in Zambia. METHODS: Data stem from the 2007 Zambia Demographic and Health Survey for women, aged 15 49 years, who reported ever having been pregnant in the 5 years preceding the survey. The linked data comprised sociodemographic and other obstetrical data, which were cleaned, recoded, and analyzed using STATA version 12 (Stata Corporation, College Station, TX, USA). Multivariate logistic regression was used to examine the association of educational attainment and other background variables. RESULTS: Women who had higher education level were more likely to attend at least four ANC visits compared to those with no education (AOR 2.8, 95% CI 1.51-5.15; p = 0.001); this was especially true in the urban areas. In addition, women with partners with higher education level were also more likely to have optimal ANC attendance (OR 2.0, 95% CI 1.3-3.1; p = 0.002). CONCLUSION: Educational attainment-associated differentials found to be linked with optimal ANC attendance in this population suggests that access to health care is still driven by inequity-related dynamics and imbalances. Given that inequity stresses are heaviest in the uneducated and probably rural and poor groups, interventions should aim to reach this group. SIGNIFICANCE: The study results will help program managers to increase access to ANC services and direct interventional efforts towards the affected subpopulations, such as the young, uneducated, and rural women. Furthermore, results will help promote maternal health education and advise policy makers and program implementers. PMID- 27379230 TI - Signal Propagation between Neuronal Populations Controlled by Micropatterning. AB - The central nervous system consists of an unfathomable number of functional networks enabling highly sophisticated information processing. Guided neuronal growth with a well-defined connectivity and accompanying polarity is essential for the formation of these networks. To investigate how two-dimensional protein patterns influence neuronal outgrowth with respect to connectivity and functional polarity between adjacent populations of neurons, a microstructured model system was established. Exclusive cell growth on patterned substrates was achieved by transferring a mixture of poly-l-lysine and laminin to a cell-repellent glass surface by microcontact printing. Triangular structures with different opening angle, height, and width were chosen as a pattern to achieve network formation with defined behavior at the junction of adjacent structures. These patterns were populated with dissociated primary cortical embryonic rat neurons and investigated with respect to their impact on neuronal outgrowth by immunofluorescence analysis, as well as their functional connectivity by calcium imaging. Here, we present a highly reproducible technique to devise neuronal networks in vitro with a predefined connectivity induced by the design of the gateway. Daisy-chained neuronal networks with predefined connectivity and functional polarity were produced using the presented micropatterning method. Controlling the direction of signal propagation among populations of neurons provides insights to network communication and offers the chance to investigate more about learning processes in networks by external manipulation of cells and signal cascades. PMID- 27379231 TI - Upconversion Nanoparticles for Bioimaging and Regenerative Medicine. AB - Nanomaterials are proving useful for regenerative medicine in combination with stem cell therapy. Nanoparticles (NPs) can be administrated and targeted to desired tissues or organs and subsequently be used in non-invasive real-time visualization and tracking of cells by means of different imaging techniques, can act as therapeutic agent nanocarriers, and can also serve as scaffolds to guide the growth of new tissue. NPs can be of different chemical nature, such as gold, iron oxide, cadmium selenide, and carbon, and have the potential to be used in regenerative medicine. However, there are still many issues to be solved, such as toxicity, stability, and resident time. Upconversion NPs have relevant properties such as (i) low toxicity, (ii) capability to absorb light in an optical region where absorption in tissues is minimal and penetration is optimal (note they can also be designed to emit in the near-infrared region), and (iii) they can be used in multiplexing and multimodal imaging. An overview on the potentiality of upconversion materials in regenerative medicine is given. PMID- 27379233 TI - Biomechanical Analysis of the Effects of Bilateral Hinged Knee Bracing. AB - This research analyzed the effect of bilateral hinged knee braces on a healthy knee from a biomechanical frame in vivo. This was accomplished by fitting a knee brace with two customized wireless force/torque (F/T) sensors that could readily record force and torque during live motion, while the kinetics at the knee were computed using the inverse dynamics of the motion capture and force plate data. Four tasks to test the brace's effects were drop vertical jumping, pivoting, stop vertical jumping, and cutting. The results showed that the hinges in the knee brace can absorb up to 18% of the force and 2.7% of the torque at the knee during various athletic motions. Thus, the hinges demonstrated minimal effect in reducing the mechanical load on the knee. There were limitations concerning the consistency of the motions performed by the subjects during the trials and the influence of the other portions of the brace to evaluate the overall effectiveness of the brace as a whole. Future works may incorporate a fatigue protocol and injured subjects to better determine the effects of the brace. There is still a need for more research on the biomechanical influence of knee braces to develop safer and more effective products. PMID- 27379232 TI - Biomaterials for the Treatment of Alzheimer's Disease. AB - Alzheimer's disease (AD) as a progressive and fatal neurodegenerative disease represents a huge unmet need for treatment. The low efficacy of current treatment methods is not only due to low drug potency but also due to the presence of various obstacles in the delivery routes. One of the main barriers is the blood brain barrier. The increasing prevalence of AD and the low efficacy of current therapies have increased the amount of research on unraveling of disease pathways and development of treatment strategies. One of the interesting areas for the latter subject is biomaterials and their applications. This interest originates from the fact that biomaterials are very useful for the delivery of therapeutic agents, such as drugs, proteins, and/or cells, in order to treat diseases and regenerate tissues. Recently, manufacturing of nano-sized delivery systems has increased the efficacy and delivery potential of biomaterials. In this article, we review the latest developments with regard to the use of biomaterials for the treatment of AD, including nanoparticles and liposomes for delivery of therapeutic compounds and scaffolds for cell delivery strategies. PMID- 27379234 TI - Erratum: Addendum: Miniaturized Technologies for Enhancement of Motor Plasticity. AB - [This corrects the article on p. 30 in vol. 4, PMID: 27148525.]. PMID- 27379235 TI - Recognition of Membrane Sterols by Polyene Antifungals Amphotericin B and Natamycin, A (13)C MAS NMR Study. AB - The molecular action of polyene macrolides with antifungal activity, amphotericin B and natamycin, involves recognition of sterols in membranes. Physicochemical and functional studies have contributed details to understanding the interactions between amphotericin B and ergosterol and, to a lesser extent, with cholesterol. Fewer molecular details are available on interactions between natamycin with sterols. We use solid state (13)C MAS NMR to characterize the impact of amphotericin B and natamycin on mixed lipid membranes of DOPC/cholesterol or DOPC/ergosterol. In cholesterol-containing membranes, amphotericin B addition resulted in marked increase in both DOPC and cholesterol (13)C MAS NMR linewidth, reflecting membrane insertion and cooperative perturbation of the bilayer. By contrast, natamycin affects little either DOPC or cholesterol linewidth but attenuates cholesterol resonance intensity preferentially for sterol core with lesser impact on the chain. Ergosterol resonances, attenuated by amphotericin B, reveal specific interactions in the sterol core and chain base. Natamycin addition selectively augmented ergosterol resonances from sterol core ring one and, at the same time, from the end of the chain. This puts forward an interaction model similar to the head-to-tail model for amphotericin B/ergosterol pairing but with docking on opposite sterol faces. Low toxicity of natamycin is attributed to selective, non-cooperative sterol engagement compared to cooperative membrane perturbation by amphotericin B. PMID- 27379229 TI - Selection and Biosensor Application of Aptamers for Small Molecules. AB - Small molecules play a major role in the human body and as drugs, toxins, and chemicals. Tools to detect and quantify them are therefore in high demand. This review will give an overview about aptamers interacting with small molecules and their selection. We discuss the current state of the field, including advantages as well as problems associated with their use and possible solutions to tackle these. We then discuss different kinds of small molecule aptamer-based sensors described in literature and their applications, ranging from detecting drinking water contaminations to RNA imaging. PMID- 27379236 TI - miRNAs As Emerging Regulators of Oligodendrocyte Development and Differentiation. AB - Chronic demyelination is a hallmark of neurological disorders such as multiple sclerosis (MS) and several leukodystrophies. In the central nervous system (CNS), remyelination is a regenerative process that is often inadequate during these pathological states. In the MS context, in situ evidence suggests that remyelination is mediated by populations of oligodendrocyte progenitor cells (OPCs) that proliferate, migrate, and differentiate into mature, myelin-producing oligodendrocytes at sites of demyelinated lesions. The molecular programming of OPCs into mature oligodendrocytes is governed by a myriad of complex intracellular signaling pathways that modulate this process. Recent research has demonstrated the importance of specific and short non-coding RNAs, known as microRNAs (miRNAs), in regulating OPC differentiation and remyelination. Fortunately, it may be possible to take advantage of numerous developmental studies (both human and rodent) that have previously characterized miRNA expression profiles from the early neural progenitor cell to the late myelin producing oligodendrocyte. Here we review much of the work to date and discuss the impact of miRNAs on OPC and oligodendrocyte biology. Additionally, we consider the potential for miRNA-mediated therapy in the context of remyelination and brain repair. PMID- 27379237 TI - Separating Putative Pathogens from Background Contamination with Principal Orthogonal Decomposition: Evidence for Leptospira in the Ugandan Neonatal Septisome. AB - Neonatal sepsis (NS) is responsible for over 1 million yearly deaths worldwide. In the developing world, NS is often treated without an identified microbial pathogen. Amplicon sequencing of the bacterial 16S rRNA gene can be used to identify organisms that are difficult to detect by routine microbiological methods. However, contaminating bacteria are ubiquitous in both hospital settings and research reagents and must be accounted for to make effective use of these data. In this study, we sequenced the bacterial 16S rRNA gene obtained from blood and cerebrospinal fluid (CSF) of 80 neonates presenting with NS to the Mbarara Regional Hospital in Uganda. Assuming that patterns of background contamination would be independent of pathogenic microorganism DNA, we applied a novel quantitative approach using principal orthogonal decomposition to separate background contamination from potential pathogens in sequencing data. We designed our quantitative approach contrasting blood, CSF, and control specimens and employed a variety of statistical random matrix bootstrap hypotheses to estimate statistical significance. These analyses demonstrate that Leptospira appears present in some infants presenting within 48 h of birth, indicative of infection in utero, and up to 28 days of age, suggesting environmental exposure. This organism cannot be cultured in routine bacteriological settings and is enzootic in the cattle that often live in close proximity to the rural peoples of western Uganda. Our findings demonstrate that statistical approaches to remove background organisms common in 16S sequence data can reveal putative pathogens in small volume biological samples from newborns. This computational analysis thus reveals an important medical finding that has the potential to alter therapy and prevention efforts in a critically ill population. PMID- 27379238 TI - Community-Acquired Pneumonia Caused by Mycoplasma pneumoniae: How Physical and Radiological Examination Contribute to Successful Diagnosis. AB - Mycoplasma pneumoniae is one of the most common causes of community-acquired pneumonia (CAP), particularly in young adults. Vital signs are usually normal except for temperature. On physical examination, general appearance is normal compared with that of typical pneumonia such as pneumococcal pneumonia patients. Mycoplasma sometimes causes ear infections such as otitis media. It is important to distinguish between typical pneumonia and atypical pneumonia such as mycoplasma pneumonia because having the right diagnosis allows for the use of the correct antibiotic to treat CAP while preventing development of drug-resistant bacteria and also decreasing medical cost. The symptoms and diagnosis of mycoplasma pneumonia is multi-fold. Auscultation of patients can demonstrate trace late inspiratory crackles or normal alveolar sounds; however, bilateral polyphonic wheezes can sometimes be heard because of bronchiolitis. With regard to radiological findings, a chest radiogragh often shows bilateral reticulonodular or patchy consolidation in both lower lobes. Pleural effusion is rarely observed in adult cases. Immunocompetent patients tend to reveal more extensive shadowing compared with immunocompromised patients. As serological diagnostic methods are not able to offer 100% reliable diagnosis, integration of physical and radiological examination is crucial to accurately diagnose mycoplasma pneumonia. Herein, I review the typical findings from physical examination and imaging patterns of patients with mycoplasma pneumonia. PMID- 27379240 TI - Drivers of Plant-Availability of Phosphorus from Thermally Conditioned Sewage Sludge as Assessed by Isotopic Labeling. AB - Urban sewage sludge is a potential source of phosphorus (P) for agriculture and represents an alternative way to recycle P as fertilizer. However, the use of thermally conditioned sewage sludge (TCSS) required an accurate assessment of its value as P-fertilizer. This work aimed at assessing the plant-availability of P from TCSS. Uptake of P by a mixture of ryegrass and fescue from TCSS and triple super phosphate (TSP) fertilizers was studied using (32)P-labeling technique in a greenhouse experiment. Phosphorus was applied at the rate of 50 mg P kg(-1).We also conducted incubation experiments considering the same treatments to assess soil microbial respiration. Applications of TCSS and TSP increased plant P uptake that is related to the root P acquisition. The P taken up by plant from soil plant-available P was lower for control compared to TSP or TCSS that was attributed to the increase of root interception of soil P. The contribution of TSP to ryegrass nutrition (Pdff%) was 55% with 22% of the applied P which was taken up by plants (CPU%). The Pdff value for TCSS was 56% with 14% of fertilizer P recovery (CPU%). Shoot biomass and total P uptake from TCSS were lower than those from TSP. As a result, the agronomic effectiveness of TCSS calculated from Pdff value (in comparison with TSP treatment) was 102%, while the AE of TCSS estimated from CPU value (in % TSP) was 64%, which is attributed to microbial activity stimulation inducing P immobilization onto soil constituents and microbial biomass during plant growth. The high C/N ratio of TCSS stimulated soil microbial biomass that competes with plant roots to acquire nutrients, such as P. As a consequence, the P taken up from either native soil or TCSS decreased in similar proportions. The AE value calculated with Pdff% took into account these interactions between soil, plant, and microbial biomass, and is less dependent on operational conditions than the AE value calculated with %Precovery. PMID- 27379239 TI - Thiamine Deficiency in Tropical Pediatrics: New Insights into a Neglected but Vital Metabolic Challenge. AB - In humans, thiamine is a micronutrient prone to depletion that may result in severe clinical abnormalities. This narrative review summarizes current knowledge on thiamine deficiency (TD) and bridges the gap between pathophysiology and clinical presentation by integrating thiamine metabolism at subcellular level with its function to vital organs. The broad clinical spectrum of TD is outlined, with emphasis on conditions encountered in tropical pediatric practice. In particular, TD is associated with type B lactic acidosis and classic forms of beriberi in children, but it is often unrecognized. Other severe acute conditions are associated with hypermetabolism, inducing a functional TD. The crucial role of thiamine in infant cognitive development is also highlighted in this review, along with analysis of the potential impact of TD in refeeding syndrome during severe acute malnutrition (SAM). This review aims to increase clinical awareness of TD in tropical settings where access to diagnostic tests is poor, and advocates for an early therapeutic thiamine challenge in resource-limited settings. Moreover, it provides evidence for thiamine as treatment in critical conditions requiring metabolic resuscitation, and gives rationale to the consideration of increased thiamine supplementation in therapeutic foods for malnourished children. PMID- 27379242 TI - Hemodynamic Functions of Fenestrated Stent Graft under Resting, Hypertension, and Exercise Conditions. AB - The aim of this study was to assess the hemodynamic performance of a patient specific fenestrated stent graft (FSG) under different physiological conditions, including normal resting, hypertension, and hypertension with moderate lower limb exercise. A patient-specific FSG model was constructed from computed tomography images and was discretized into a fine unstructured mesh comprising tetrahedral and prism elements. Blood flow was simulated using Navier-Stokes equations, and physiologically realistic boundary conditions were utilized to yield clinically relevant results. For a given cycle-averaged inflow of 2.08 L/min at normal resting and hypertension conditions, approximately 25% of flow was channeled into each renal artery. When hypertension was combined with exercise, the cycle averaged inflow increased to 6.39 L/min but only 6.29% of this was channeled into each renal artery, which led to a 438.46% increase in the iliac flow. For all the simulated scenarios and throughout the cardiac cycle, the instantaneous flow streamlines in the FSG were well organized without any notable flow recirculation. This well-organized flow led to low values of endothelial cell activation potential, which is a hemodynamic metric used to identify regions at risk of thrombosis. The displacement forces acting on the FSG varied with the physiological conditions, and the cycle-averaged displacement force at normal rest, hypertension, and hypertension with exercise was 6.46, 8.77, and 8.99 N, respectively. The numerical results from this study suggest that the analyzed FSG can maintain sufficient blood perfusion to the end organs at all the simulated conditions. Even though the FSG was found to have a low risk of thrombosis at rest and hypertension, this risk can be reduced even further with moderate lower limb exercise. PMID- 27379241 TI - Bone Marrow Aspirate in the Treatment of Chondral Injuries. AB - The ability of mesenchymal stem cells (MSCs) to transdifferentiate into a desired cell lineage has captured the imagination of scientists and clinicians alike. The limited ability for chondrocytes to regenerate in chondral injuries has raised the concept of using MSCs to help regenerate and repair damaged tissue. The expansion of cells in a laboratory setting to be delivered back to the patient is too costly for clinical use in the present tough economic climate. This process is slow with due to the complexity of trying to imitate the natural environment and biological stimulation of chondral cell replication and proliferation. Bone marrow aspirate concentrate (BMAC) has the potential to provide an easily accessible and readily available source of MSCs with key growth factors that can be used in treating chondral injuries. This review summarizes the underlying basic science of MSCs and the therapeutic potential of BMAC. PMID- 27379243 TI - Standard Surgical Skin Markers Should Be Avoided for Intraoperative Vein Graft Marking during Cardiac and Peripheral Bypass Operations. PMID- 27379244 TI - Systematic Identification of Anti-Fungal Drug Targets by a Metabolic Network Approach. AB - New antimycotic drugs are challenging to find, as potential target proteins may have close human orthologs. We here focus on identifying metabolic targets that are critical for fungal growth and have minimal similarity to targets among human proteins. We compare and combine here: (I) direct metabolic network modeling using elementary mode analysis and flux estimates approximations using expression data, (II) targeting metabolic genes by transcriptome analysis of condition specific highly expressed enzymes, and (III) analysis of enzyme structure, enzyme interconnectedness ("hubs"), and identification of pathogen-specific enzymes using orthology relations. We have identified 64 targets including metabolic enzymes involved in vitamin synthesis, lipid, and amino acid biosynthesis including 18 targets validated from the literature, two validated and five currently examined in own genetic experiments, and 38 further promising novel target proteins which are non-orthologous to human proteins, involved in metabolism and are highly ranked drug targets from these pipelines. PMID- 27379245 TI - Genetic Evaluation and Use of Chromosome Microarray in Patients with Isolated Heart Defects: Benefits and Challenges of a New Model in Cardiovascular Care. AB - Congenital heart defects (CHDs) are common birth defects and result in significant morbidity and global economic impact. Genetic factors play a role in most CHDs; however, identification of these factors has been historically slow due to technological limitations and incomplete understanding of the impact of human genomic variation on normal and abnormal cardiovascular development. The advent of chromosome microarray (CMA) brought tremendous gains in identifying chromosome abnormalities in a variety of human disorders and is now considered part of a standard evaluation for individuals with multiple congenital anomalies and/or neurodevelopmental disorders. Several studies investigating use of CMA found that this technology can identify pathogenic copy-number variations (CNVs) in up to 15-20% of patients with CHDs with other congenital anomalies. However, there have been fewer studies exploring the use of CMA for patients with isolated CHDs. Recent studies have shown that the diagnostic yield of CMA in individuals with seemingly isolated CHD is lower than in individuals with CHDs and additional anomalies. Nevertheless, positive CMA testing in this group supports chromosome variation as one mechanism underlying the development of isolated, non-syndromic CHD - either as a causative or risk-influencing genetic factor. CMA has also identified novel genomic variation in CHDs, shedding light on candidate genes and pathways involved in cardiac development and malformations. Additional studies are needed to further address this issue. Early genetic diagnosis can enhance the medical management of patients and potentially provide crucial information about recurrence. This information is critical for genetic counseling of patients and family members. In this review, we review CMA for the non-genetics cardiology provider, offer a summary of CNV in isolated CHDs, and advocate for the use of CMA as part of the cardiovascular genetics evaluation of patients with isolated CHDs. We also provide perspective regarding the benefits and challenges that lie ahead for this model in the clinical setting. PMID- 27379246 TI - Association of Temperament and Acute Stress Responsiveness with Productivity, Feed Efficiency, and Methane Emissions in Beef Cattle: An Observational Study. AB - The aim of this study was to assess individual differences in temperament and stress response and quantify their impact on feed efficiency, performance, and methane (CH4) emissions in beef cattle. Eighty-four steers (castrated males) (Charolais or Luing) were used. Temperament was assessed using two standardized tests: restlessness when restrained [crush score (CS)] and flight speed (FS) on release from restraint. Over a 56-day period individual animal dry matter intake (DMI) and weekly body weight was measured. Ultrasound fat depth was measured at the end of 56 days. Average daily gain (ADG), feed conversion ratio (FCR), and residual feed intake (RFI) were calculated. After the 56-day test period, animals were transported in groups of six/week to respiration chamber facilities. Blood samples were taken before and 0, 3, 6, and 9 h after transport. Plasma cortisol, creatine kinase (CK), glucose, and free fatty acids (FFA) were determined to assess physiological stress response. Subsequently, CH4 emissions were measured over a 3-day period in individual respiration chambers. CS (1.7 +/- 0.09) and FS (1.6 +/- 0.60 m/s) were repeatable (0.63 and 0.51, respectively) and correlated (r = 0.36, P < 0.001). Plasma cortisol, CK, and FFA concentrations increased after transport (P = 0.038, P = 0.006, and P < 0.001, respectively). Temperament (CS) and CK concentration were correlated (r = 0.29; P = 0.015). The extreme group analysis reveals that excitable animals (FS; P = 0.032) and higher stress response (cortisol, P = 0.007; FFA, P = 0.007; and CK, P = 0.003) were associated with lower DMI. ADG was lower in more temperamental animals (CS, P = 0.097, and FS, P = 0.030). Fat depth was greater in steers showing calmer CS (P = 0.026) and lower plasma CK (P = 0.058). Temperament did not show any relationship with RFI or CH4 emissions. However, steers with higher cortisol showed improved feed efficiency (lower FCR and RFI) (P < 0.05) and greater CH4 emissions (P = 0.017). In conclusion, agitated temperament and higher stress responsiveness is detrimental to productivity. A greater stress response is associated with a reduction in feed intake that may both increase the efficiency of consumed feed and the ratio of CH4 emissions/unit of feed. Therefore, temperament and stress response should be considered when designing strategies to improve efficiency and mitigate CH4 emissions in beef cattle. PMID- 27379247 TI - Drug Target Identification and Prioritization for Treatment of Ovine Foot Rot: An In Silico Approach. AB - Ovine foot rot is an infection of the feet of sheep, mainly caused by Dichelobacter nodosus. In its virulent form, it is highly contagious and debilitating, causing significant losses in the form of decline in wool growth and quality and poor fertility. Current methods of treatment are ineffective in complete eradication. Effective antibiotic treatment of foot rot is hence necessary to ensure better outcomes during control phases by reduction in culling count and the possibility of carriers of the infection. Using computational approaches, we have identified a set of 297 proteins that are essential to the D. nodosus and nonhomologous with sheep proteins. These proteins may be considered as potential vaccine candidates or drug targets for designing antibiotics against the bacterium. This core set of drug targets have been analyzed for pathway annotation to identify 67 proteins involved in unique bacterial pathways. Choke point analysis on the drug targets identified 138 choke-point proteins, 29 involved in unique bacterial pathways. Subcellular localization was also predicted for each target to identify the ones that are membrane associated or secreted extracellularly. In addition, a total of 13 targets were identified that are common in at least 10 pathogenic bacterial species. PMID- 27379248 TI - The Preclinical Research Progress of Stem Cells Therapy in Parkinson's Disease. AB - Parkinson's disease (PD) is a type of degenerative disorder of the basal ganglia, causing tremor at rest, muscle rigidity hypokinesia, and dementia. The effectiveness of drug treatments gradually diminishes because the conversion to dopamine within the brain is increasingly disrupted by the progressive degeneration of the dopaminergic terminals. After long-term treatment, most patients with PD suffer from disability that cannot be satisfactorily controlled. To solve these issues, stem cells have recently been used for cell therapy of PD. In this review, the characteristics of different stem cells and their therapeutic effects on PD treatment will be discussed. PMID- 27379249 TI - A Long-Acting BMP-2 Release System Based on Poly(3-hydroxybutyrate) Nanoparticles Modified by Amphiphilic Phospholipid for Osteogenic Differentiation. AB - We explored a novel poly(3-hydroxybutyrate) (PHB) nanoparticle loaded with hydrophilic recombinant human BMP-2 with amphiphilic phospholipid (BPC-PHB NP) for a rapid-acting and long-acting delivery system of BMP-2 for osteogenic differentiation. The BPC-PHB NPs were prepared by a solvent evaporation method and showed a spherical particle with a mean particle size of 253.4 nm, mean zeta potential of -22.42 mV, and high entrapment efficiency of 77.18%, respectively. For BPC-PHB NPs, a short initial burst release of BMP-2 from NPs in 24 h was found and it has steadily risen to reach about 80% in 20 days for in vitro test. BPC-PHB NPs significantly reduced the burst release of BMP-2, as compared to that of PHB NPs loading BMP-2 without PL (B-PHB NPs). BPC-PHB NPs maintained the content of BMP-2 for a long-term osteogenic differentiation. The OCT-1 cells with BPC-PHB NPs have high ALP activity in comparison with others. The gene markers for osteogenic differentiation were significantly upregulated for sample with BPC PHB NPs, implying that BPC-PHB NPs can be used as a rapid-acting and long-acting BMP-2 delivery system for osteogenic differentiation. PMID- 27379250 TI - The Influence of Humidity on Assessing Irritation Threshold of Ammonia. AB - A large number of occupational exposure limit values (OELs) are based on avoiding of sensory irritation of the eyes and the upper respiratory tract. In order to investigate the chemosensory effect range of a chemical, odor and sensory irritation thresholds (lateralization thresholds, LTs) can be assessed. Humidity affects olfactory function and thus influences odor thresholds; however, a similar effect has not been shown for sensory irritation thresholds. The purpose of the present study was to explore whether LTs for ammonia vapor vary depending on the water vapor content of the inspired stimulus. Eight healthy nonsmoking volunteers were simultaneously exposed to ammonia vapor through one nostril and clean air through the other and were asked to determine which nostril received the chemical. Within experimental runs, ascending ammonia concentrations (60-350 ppm) that were either dry or humidified were administered at fixed time intervals. Geometric mean LTs obtained at wet (181 ppm) or dry (172 ppm) conditions did not differ significantly (P = 0.19) and were within the range of those reported by previous studies. These results suggest that humidity is not a critical factor in determining sensory irritation thresholds for ammonia, and future studies will examine if these findings are transferable to sensory irritation thresholds for other chemicals. PMID- 27379251 TI - Clinical, Radiographic and Microbiological Evaluation of High Level Laser Therapy, a New Photodynamic Therapy Protocol, in Peri-Implantitis Treatment; a Pilot Experience. AB - Aim. Endosseous implants are widely used to replace missing teeth but mucositis and peri-implantitis are the most frequent long-term complications related with dental implants. Removing all bacterial deposits on contaminated implant surface is very difficult due to implant surface morphology. The aim of this study was to evaluate the bactericidal potential of photodynamic therapy by using a new high level laser irradiation protocol associated with hydrogen peroxide in peri implantitis. Materials and Methods. 10 patients affected by peri-implantitis were selected for this study. Medical history, photographic documentation, periodontal examination, and periapical radiographs were collected at baseline and 6 months after surgery. Microbiological analysis was performed with PCR Real Time. Each patient underwent nonsurgical periodontal therapy and surgery combined with photodynamic therapy according to High Level Laser Therapy protocol. Results. All peri-implant pockets were treated successfully, without having any complication and not showing significant differences in results. All clinical parameters showed an improvement, with a decrease of Plaque Index (average decrease of 65%, range 23-86%), bleeding on probing (average decrease of 66%, range 26-80%), and probing depth (average decrease of 1,6 mm, range 0,46-2,6 mm). Periapical radiographs at 6 months after surgery showed a complete radiographic filling of peri-implant defect around implants treated. Results showed a decrease of total bacterial count and of all bacterial species, except for Eikenella corrodens, 6 months after surgery. Conclusion. Photodynamic therapy using HLLT appears to be a good adjunct to surgical treatment of peri-implantitis. PMID- 27379252 TI - Animal Model of Gestational Diabetes Mellitus with Pathophysiological Resemblance to the Human Condition Induced by Multiple Factors (Nutritional, Pharmacological, and Stress) in Rats. AB - This study attempts to develop an experimental gestational diabetes mellitus (GDM) animal model in female Sprague-Dawley rats. Rats were fed with high fat sucrose diet, impregnated, and induced with Streptozotocin and Nicotinamide on gestational day 0 (D0). Sleeping patterns of the rats were also manipulated to induce stress, a lifestyle factor that contributes to GDM. Rats were tested for glycemic parameters (glucose, C-peptide, and insulin), lipid profiles (total cholesterol, triglycerides, HDL, and LDL), genes affecting insulin signaling (IRS 2, AKT-1, and PCK-1), glucose transporters (GLUT-2 and GLUT-4), proinflammatory cytokines (IL-6, TNF-alpha), and antioxidants (SOD, CAT, and GPX) on D6 and D21. GDM rats showed possible insulin resistance as evidenced by high expression of proinflammatory cytokines, PCK-1 and CRP. Furthermore, low levels of IRS-2 and AKT-1 genes and downregulation of GLUT-4 from the initial to final phases indicate possible defect of insulin signaling. GDM rats also showed an impairment of antioxidant status and a hyperlipidemic state. Additionally, GDM rats exhibited significantly higher body weight and blood glucose and lower plasma insulin level and C-peptide than control. Based on the findings outlined, the current GDM animal model closely replicates the disease state in human and can serve as a reference for future investigations. PMID- 27379255 TI - The Onstep Method for Inguinal Hernia Repair: Operative Technique and Technical Tips. AB - Inguinal hernia repair is one of the most common surgical procedures and several different surgical techniques are available. The Onstep method is a new promising technique. The technique is simple with a number of straightforward steps. This paper provides a full description of the technique together with tips and tricks to make it easy and without complications. PMID- 27379254 TI - Knowledge and attitudes toward corneal donation among Singaporean youth: a cross sectional study. AB - BACKGROUND: To assess the knowledge of Singaporean youth regarding corneal donation and gauge their willingness to donate their corneas. METHODS: We conducted a cross-sectional study among 500 students from five tertiary institutions in Singapore. All students answered self-administered questionnaires which included seven questions that tested knowledge and three questions that determined willingness to donate corneas. RESULTS: Among 500 Singaporean youth aged 18 to 25, most students (73.2 %) answered 3 or fewer of the 7 questions about corneal donation correctly. With regards to the willingness to donate, 155 (31 %) were willing to donate their corneas, 111 (22.2 %) were not willing to donate their corneas, and 234 (46.8 %) were undecided. Willingness to donate corneas was associated with an older age group (21 to 25 years old), those who are non-Muslims, and have good basic knowledge. Particularly, students with good basic knowledge were 1.71 times more likely to willingly donate their corneas. CONCLUSION: The knowledge of the Singaporean youth regarding corneal donation and transplantation is poor. Since insufficient information was cited as the most common reason for being undecided in regards to corneal donation, specific and tailored programs to increase knowledge and awareness are needed to convince the youth to support corneal donation. PMID- 27379256 TI - Mortality and Pathology Associated with Highly Pathogenic Avian Influenza H5N1 Outbreaks in Commercial Poultry Production Systems in Nigeria. AB - Commercial layer-type, pullet, cockerel, and broiler chicken flocks infected with highly pathogenic avian influenza (HPAI) H5N1 in Nigeria between 2006 and 2008 were investigated for morbidity, mortality, and pathology. Of the one hundred and fifty-three (153) farms confirmed with HPAI infection, one hundred and twenty seven (127) were layer-type farms, nine (9) were pullet and broiler farms each, and eight (8) were cockerel rearing farms. This study revealed the morbidity and mortality of a total of 939,620 commercial layer chickens, 16,421 pullets, 3,109 cockerels, and 6,433 broilers. Mortality rates were 11.11% in commercial layers, 26.84% in pullets, 45.51% in cockerels, and 73.92% in broilers in a total of eighteen (18) states and the Federal Capital Territory, Abuja. A total of 316 carcasses were examined of which 248 were commercial layer, 25 were pullet, 14 were cockerel, and 29 were broiler. Main clinical and pathologic findings were observed in the nervous, circulatory, respiratory, integumentary, musculoskeletal, hemopoietic, gastrointestinal, and reproductive systems and, occasionally, lesions were generally nonspecific and multisystemic. Lesions occurred more frequently, severely, and in most of the carcasses examined, irrespective of chicken type. PMID- 27379253 TI - Histone Acetylation and Its Modifiers in the Pathogenesis of Diabetic Nephropathy. AB - Diabetic nephropathy (DN) remains a leading cause of mortality worldwide despite advances in its prevention and management. A comprehensive understanding of factors contributing to DN is required to develop more effective therapeutic options. It is becoming more evident that histone acetylation (HAc), as one of the epigenetic mechanisms, is thought to be associated with the etiology of diabetic vascular complications such as diabetic retinopathy (DR), diabetic cardiomyopathy (DCM), and DN. Histone acetylases (HATs) and histone deacetylases (HDACs) are the well-known regulators of reversible acetylation in the amino terminal domains of histone and nonhistone proteins. In DN, however, the roles of histone acetylation (HAc) and these enzymes are still controversial. Some new evidence has revealed that HATs and HDACs inhibitors are renoprotective in cellular and animal models of DN, while, on the other hand, upregulation of HAc has been implicated in the pathogenesis of DN. In this review, we focus on the recent advances on the roles of HAc and their covalent enzymes in the development and progression of DN in certain cellular processes including fibrosis, inflammation, hypertrophy, and oxidative stress and discuss how targeting these enzymes and their inhibitors can ultimately lead to the therapeutic approaches for treating DN. PMID- 27379257 TI - Clinical Evaluation of Etched Enamel Discoloration following Immediate and Delayed Exposure to Colored Agents. AB - Introduction. The aim was to evaluate etched enamel discoloration following immediate and delayed exposure to colored agents. Method & Material. 64 premolars were divided into four groups. Buccal surface of the teeth was divided into two halves and baseline color values were measured. One half was covered and the other half was etched and dried. In first and second groups, the patients did not eat any colored agents for the next 24 hours. Both halves were colorimetered after 48 hours and 1 month, respectively. In third and fourth groups, the process was similar, but the patients drank cola and avoid eating any other colored agents and the teeth were colorimetered after 48 hours and 1 month, respectively. Color change values (DeltaE) of each half were calculated according to CIE lab system. Sign test was used to compare values of etched and unetched halves. P < 0.08 was set as significant. Results. A significant difference was observed in groups III and IV regarding comparison of DeltaE of the etched and control enamel (P = 0.077). Conclusion. Exposure of etched enamel to colored agents in the first 24 hours after etching can affect its color which remains at least for one month. PMID- 27379258 TI - Obstetric Scar Endometriosis: Retrospective Study on 19 Cases and Review of the Literature. AB - Endometriosis is defined as the presence of functioning endometrial tissue outside the uterine cavity. This disease is one of the most common gynecologic disorders in reproductive age women. It generally occurs in pelvic cavity. But extrapelvic location has been defined (such as extremities, central nervous system, lungs, pleurae, liver, umbilicus, pericardium, urinary tract, intestines, and surgical scar tissue). Scar endometriosis is a rare disease and defined as presence of endometriotic lesions on the abdominal (such as cesarean section and hysterectomy) or vaginal (episiotomy) excision line. It is difficult to diagnose due to the extreme variability in presentation. The symptoms are nonspecific, typically involving pain, swelling at the incision site at the time of menstruation. Excision and histopathologic examination are necessary for diagnosis. We present a case series of obstetric scar endometriosis and review of the literature. PMID- 27379259 TI - Exposure of Prostate to Lipopolysaccharide and Hypoxia Potentiates Neoplastic Behavior and Risk for Prostate Carcinogenesis In Vivo. AB - A number of studies showed that men from tropical countries have higher burden of prostate cancer similar to data from USA. We developed a translational model to examine whether exposure to microbial inflammation-inducing molecule lipopolysacchride LPS was associated with prostatic cell transformation to more proliferative phenotype as indicated by PSA secretion. Immunocompetent adult mice were divided into two groups; the first group received a local prostate inoculation with E. coli, while the second group received inoculation with sterile solution of saline as vehicle. At the end of 6 days, the PSA values were measured and compared. In the second experiment, two groups of animals were involved. The test group received two drops of the hydrogen peroxide orally for six to seven days to induce hypoxia, while the control group received normal saline. Blood samples were evaluated for serum level of PSA. Result showed a 2 fold increase in level of PSA compared to the control mice in the E. coli inoculated-LPS exposed animals. In addition, exposure of the animals to hypoxic stress resulted in 3.5 fold increase in the serum PSA compared to the control group, which was found to be statistically significant (P < 0.0001). In conclusion, our data shows that chronic prostatic infection and exposure to inflammatory stimulus, especially LPS, may alter the phenotype of prostate epithelial cells for increased PSA secretion, a known cancer-like behavior; this is mediated by compromised redox state and oxidative stress injury. We propose that exposure of the prostate epithelial cells to lipopolysaccharide (LPS) promotes chronic inflammation and risk of neoplastic behavior of the prostate in vivo; this may explain the high rate of prostate cancer in tropics. PMID- 27379260 TI - Dynamic of Plant Composition and Regeneration following Windthrow in a Temperate Beech Forest. AB - The effects of soil pedoturbation (i.e., pit and mound microtopography, PM) on development of herbaceous plant species and woody species regeneration were examined in a temperate beech forest (Fagus orientalis Lipsky) in northern Iran. We recorded the vegetation in 20 pairs of disturbed and adjacent undisturbed plots and established a chronosequence of PM ages to study the effect of time since microsite formation on cover percent of herbaceous plants and woody regeneration status. According to our findings, Carex acutiformis L., Sambucus ebulus L., Brachypodium pinnatum L., and Cyclamen coum L. are found only in the PM microsites, whereas the Equisetum ramosissimum L. is recorded only under closed canopy. The coverage percent of Rubus caesius L. increased in PM microsites compared to closed canopy intensively. In addition, Albizia julibrissin Durazz. is detected in PM microsite, whereas the Acer cappadocicum B. and Prunus persica L. species were recorded only under closed canopy. We found significant differences in understory species diversity between different ages of PM, and disturbed and adjacent undisturbed plots. Our study supports that the PM complex will create a mosaic of environmental conditions. This environmental heterogeneity could be responsible for the diversity of herbaceous plant species and regeneration of woody species. PMID- 27379261 TI - Complementary N Uptake Strategies between Tree Species in Tropical Rainforest. AB - Within tree communities, the differential use of soil N mineral resources, a key factor in ecosystem functioning, may reflect functional complementarity, a major mechanism that could explain species coexistence in tropical rainforests. Eperua falcata and Dicorynia guianensis, two abundant species cooccurring in rainforests of French Guiana, were chosen as representative of two functional groups with complementary N uptake strategies (contrasting leaf delta (15)N signatures related to the delta (15)N of their soil N source, NO3 (-) or NH4 (+)). The objectives were to investigate if these strategies occurred under contrasted soil N resources in sites with distinct geological substrates representative of the coastal rainforests. Results showed that species displayed contrasting leaf delta (15)N signatures on both substrates, confirming their complementary N uptake strategy. Consequently, their leaf (15)N can be used to trace the presence of inorganic N-forms in soils (NH4 (+) and NO3 (-)) and thus to indicate the capacity of soils to provide each of these two N sources to the plant community. PMID- 27379263 TI - Adaptogenic Activity of Lyophilized Hydroethanol Extract of Pandanus odoratissimus in Swiss Albino Mice. AB - Background. The leaves of Pandanus odoratissimus Linn have been widely used in Ayurveda to treat a variety of common and stress related disorders. In the present investigation, hydroethanol extract of leaves of Pandanus odoratissimus Linn (LEPO) were evaluated for antistress activity in normal and stress induced mice. Furthermore, the extract was studied for nootropic (adaptogenic) activity in mice and in vitro antioxidant potential to correlate with its adaptogenic and antistress activity. LEPO (100 and 200 mg/kg p.o) was evaluated against forced swimming endurance stress test, anoxia stress tolerance and immobilization stress and chronic cold resistant stress tests, and biomarkers (serum glucose, Corticosterone, WBC, RBC, and DLC count) to assess the antistress activity in mice. Withania somnifera (WS) (100 mg/kg p.o) was selected as reference standard. The parameters like anoxia stress tolerance time were recorded in anoxia stress and estimation of biochemical marker levels and determination of organs weight were carried out in immobilization stress models. Results. Concomitant treatment with LEPO 200 mg/kg significantly increased in anoxia stress tolerance time. Dose dependent significant reduction in serum glucose, corticosterone, and WBC, RBC, and DLC was observed in immobilisation stress model as compared to stressed group. LEOP 200 mg/kg and WS 100 mg/kg significantly reversed/inhibited the stress induced changes in these parameters. The results from the present study indicate that these values also express that dose dependent significant adaptogenic activity in stressed animals. Conclusion. The present study provides scientific support for the antistress (adaptogenic) and nootropic activities of lyophilized hydroethanol extract of Pandanus odoratissimus Linn and substantiate the traditional claims for the usage of Pandanus in stress induced disorders. PMID- 27379262 TI - Knowledge and Attitude of Faculty Members Working in Dental Institutions towards the Dental Treatment of Patients with HIV/AIDS. AB - Background. Dentists have an ethical responsibility to provide treatment to HIV infected patients, particularly because oral lesions are common among these patients. However, there are no official guidelines as to how to treat people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLWHA) or how to screen for potentially infectious people. Materials and Method. A descriptive cross-sectional questionnaire based study which assessed the knowledge and attitude of the faculty members towards the treatment of patients with HIV/AIDS was carried out in the Sudha Rustagi College of Dental Sciences, Faridabad, and Maulana Azad Institute of Dental Sciences, New Delhi. Results. The willingness to treat patients with HIV was found to be 86.0% among the faculty members in the present study. The majority (79%) of the faculty members thought that treating an HIV-positive patient is ethical responsibility of the dentist. There was a positive attitude (88.0%) among faculty members that routine dental care should be a part of the treatment of patients with HIV/AIDS. Conclusion. The level of knowledge regarding HIV and AIDS was acceptable in the present study. However, continuing dental education (CDE) programmes should be conducted on a regular basis for updating the knowledge level of the faculty members towards the dental treatment of patients with HIV/AIDS patients. PMID- 27379264 TI - Bayesian Perspective on Random Censored Survival Data. AB - A unit is said to be randomly censored when the information on time occurrence of an event is not available due to either loss to followup, withdrawal, or nonoccurrence of the outcome event before the end of the study. It is assumed in independent random/noninformative censoring that each individual has his/her own failure time T and censoring time C; however, one can only observe the random vector, say, (X; delta). The classical approach is considered for analysing the generalised exponential distribution with random or noninformative censored samples which occur most often in biological or medical studies. The Bayes methods are also considered via a numerical approximation suggested by Lindley in 1980 and that of the Laplace approximation procedure developed by Tierney and Kadane in 1986 with assumed informative priors alongside linear exponential loss function and squared error loss function. A simulation study is carried out to compare the estimators proposed in this paper. Two datasets have also been illustrated. PMID- 27379265 TI - Optical Fiber-Based Steady State and Fluorescence Lifetime Spectroscopy for Rapid Identification and Classification of Bacterial Pathogens Directly from Colonies on Agar Plates. AB - Fluorescence spectroscopy was examined as a potential technique for identification and classification of bacterial pathogens. Colonies of Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhi, and Klebsiella pneumoniae on agar plates were measured directly using a laboratory spectrofluorimeter coupled with optical fiber. Steady state fluorescence spectra were collected following excitation at 280 nm (tryptophan) and 380 nm (NADH). Results showed that fluorescence lifetime decays of tryptophan at 280 nm excitation from the four organisms were best described with triexponential fit and it reveals the existence of different protein conformation. The emission spectroscopy of the four bacteria at 380 nm excitation (NADH) provided better classification (100% of original grouped cases correctly classified and 98.1% of cross-validated grouped cases correctly classified) than that of 280 nm excitation (tryptophan). Our results demonstrated that optical fiber-based fluorescence identification and classification of bacteria is rapid, easy to perform, and of low cost compared to standard methods. PMID- 27379266 TI - A Single Surgeon's Experience with Open, Laparoscopic, and Robotic Partial Nephrectomy. AB - Objective. To report the perioperative outcomes of patients treated with partial nephrectomy by a single surgeon using three surgical modalities-open, laparoscopic, and robotic. Methods. Between August 2006 and February 2012, 106 consecutive patients underwent open partial nephrectomy (OPN) (n = 23), laparoscopic partial nephrectomy (LPN) (n = 48), and robotic partial nephrectomy (RPN) (n = 35) by a single surgeon. Clinical variables, operative parameters, and renal functional outcomes were analyzed. Results. Preoperative patient characteristics were similar except for baseline glomerular filtration rate (GFR), which was highest in the RPN group (P = 0.004). Surgery time was longest in the RPN group (244 minutes) and shortest in the OPN group (163 minutes, P < 0.0001). Patients who had OPN had the highest incidence of 30-day complications (30%), while the RPN approach had the lowest (14%, P = 0.008). Conclusions. When performed by a single surgeon, robotic partial nephrectomy appears to be associated with fewer complications than both open and laparoscopic partial nephrectomy. Kidney function was not affected by surgical approach. PMID- 27379267 TI - Sustainable Supplier Performance Evaluation and Selection with Neofuzzy TOPSIS Method. AB - Supplier selection plays an important role in the supply chain management and traditional criteria such as price, quality, and flexibility are considered for supplier performance evaluation in researches. In recent years sustainability has received more attention in the supply chain management literature with triple bottom line (TBL) describing the sustainability in supply chain management with social, environmental, and economic initiatives. This paper explores sustainability in supply chain management and examines the problem of identifying a new model for supplier selection based on extended model of TBL approach in supply chain by presenting fuzzy multicriteria method. Linguistic values of experts' subjective preferences are expressed with fuzzy numbers and Neofuzzy TOPSIS is proposed for finding the best solution of supplier selection problem. Numerical results show that the proposed model is efficient for integrating sustainability in supplier selection problem. The importance of using complimentary aspects of sustainability and Neofuzzy TOPSIS concept in sustainable supplier selection process is shown with sensitivity analysis. PMID- 27379268 TI - Ichnocarpus frutescens Ameliorates Experimentally Induced Convulsion in Rats. AB - The present study was carried out to evaluate the anticonvulsant activity and probable mechanism of action of the methanol root extract from I. frutescens (MEIF) using different experimental animal models. Anticonvulsant activity of the single dose of MEIF (100, 200, and 400 mg/kg, p.o.) was evaluated in maximal electroshock- (MES-), pentylenetetrazole- (PTZ-), and isoniazid- (INH-) induced convulsions models in rats. The levels of gamma-amino butyric acid (GABA), glutamate, GABA-transaminase (GABA-T) activity and oxidative stress markers were measured in pretreated rat's brain homogenate to corroborate the mechanism of observed anticonvulsant activity. MEIF (200-400 mg/kg, p.o.) protected the animals in all the behavioral models used. Pretreatment of MEIF (200-400 mg/kg, p.o.) and diazepam (1.0 mg/kg, i.p.) to the animals in INH-induced convulsion model showed 100% and 80% protection, respectively, as well as significant restoration of GABA and glutamate level in the rat's brain. MEIF and vigabatrin (50 mg/kg, i.p.) reduced the PTZ-induced increase in the activity of GABA-T (46%) in the brain. Further, MEIF reversed the PTZ-induced increase in lipid peroxidase (LPO) and decrease in reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. The findings of this study validate the anticonvulsant activity of I. frutescens. PMID- 27379269 TI - Synthesis and Antimicrobial Screening of Novel 4-Substituted Phenyl-5-[1-(4 fluorophenyl)-1,3-dihydroisobenzofuran-5-yl]-2H-1,2,4-triazole-3-thiones. AB - The paper describes a convenient method for the preparation of 4-substituted phenyl-5-[1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-yl]-2H-1,2,4-triazole-3 thiones. The structures of the synthesized compounds are established by the results of LCMS, (1)H NMR, (13)C NMR, and IR and elemental analyses. The mercaptotriazoles are indicated to be in thione form by (1)H NMR spectra. All the synthesized compounds have been screened for antibacterial and antifungal activities. Compounds 12d and 12h exhibit encouraging results, while the remaining compounds show moderate activities. On the basis of spectral studies, formation of 2-amino-1,3,4-thiadiazoles from the isobenzofuran acyl thiosemicarbazides 11(a-h) is ruled out. PMID- 27379270 TI - Determining Nitrate and Nitrite Content in Beverages, Fruits, Vegetables, and Stews Marketed in Arak, Iran. AB - Background and Objectives. Presence of excessive nitrite and nitrate in foodstuff can have toxic and carcinogenic effects on humans. This study is aimed at measuring nitrate and nitrite in different foodstuffs available in Arak city market, Iran, in 2013. Methods. Totally 323 samples including stew (102 samples), beverage (116 samples), fruit (55 samples), and vegetables (50 samples) were randomly collected and analyzed according to official AOAC method 973 and ISO 6635 through spectrophotometric method. Results. Average concentration of nitrate and nitrite in the samples was 6.58-136.76, 1.52-38.22 mg kg(-1) or liter, respectively. Presence of nitrate and nitrite was confirmed in all samples. High levels of nitrate and nitrite were observed in celery and ghormeh stew; and lower level of nitrate and nitrite was found in traditionally produced vinegar, verjuice, and tomato. Conclusions. It was found that the mean values for nitrite in investigated products were higher than ADI levels of WHO. PMID- 27379271 TI - Response of Yield and Yield Components of Tef [Eragrostis tef (Zucc.) Trotter] to Tillage, Nutrient, and Weed Management Practices in Dura Area, Northern Ethiopia. AB - The low average grain yield (0.7 ton ha(-1)) of tef in Ethiopia is mainly attributed to low soil fertility, and inappropriate tillage and weeds control practices. Despite this, limited scientific information has been documented so far on their interaction effects on tef crop productivity in northern Ethiopia. The objective of this study was to assess the separate and interaction effects of tillage, fertilizer, and weed control practices on tef yield and yield components in the conditions of northern Ethiopia. A two-year study (2008-2009) was conducted using split-split-plot design with three replications. In the main plot, three tillage treatments: conventional tillage (6 times tillage passes) (T1), four times tillage passes (T2), and reduced tillage (single tillage pass at sowing) (T3) were applied. The fertilizer treatments in the subplots were: no fertilizer (F1); 23 kg N ha(-1) (F2); 23 kg N ha(-1) and 10 kg P ha(-1) (F3); 23 kg N ha(-1) and 2.5 ton manure ha(-1) (F4); and 2.5 ton manure ha(-1) (F5). The sub-subplot weed control treatments included farmer weed control practice or hand weeding (W1); 2,4 D at 0.75 kg ha(-1) at five-leaf stage; 2,4 D at 0.75 kg ha(-1) at six-leaf stage; 2,4 D at 1.5 kg ha(-1) at five-leaf stage; and 2,4 D at 1.5 kg ha(-1) at six-leaf stage. This study showed that the separate and interaction effects of tillage, fertilizer, and weed control practices significantly affected tef crop yield and yield components in both crop seasons. T2 increased tef yield by >42% over the other tillage and F3 increased yield by >21% over the other fertilizer treatments. Grain yield increased by >23% due to W1. This study thus suggested that promising treatments such as T2, F3, and W1 should be demonstrated at on-farm fields in order to evaluate their performance at farmers' conditions. PMID- 27379272 TI - In Vitro Intestinal Permeability Studies and Pharmacokinetic Evaluation of Famotidine Microemulsion for Oral Delivery. AB - The absolute bioavailability of famotidine after oral administration is about 40 45% and absorbance only in the initial part of small intestine may be due to low intestinal permeability. Hence, an olive oil based microemulsion formulation with Tween-80 as surfactant and PEG-400 as cosurfactant was developed by using water titration method with the aim of enhancing the intestinal permeability as well as oral bioavailability. In vitro drug permeation in intestine after 8 h for all formulations varied from 30.42% to 78.39% and most of the formulations showed enhanced permeation compared to pure drug (48.92%). Famotidine microemulsion exhibited the higher absorption and C max? achieved from the optimized famotidine formulation (456.20 ng.h/ml) was higher than the standard (126.80 ng.h/mL). It was found that AUC0-24 h obtained from the optimized famotidine test formulation (3023.5 ng.h/mL) was significantly higher than the standard famotidine (1663.3 ng.h/mL). F-1 demonstrated a longer (6 h) T max? compared with standard drug (2 h) and sustained the release of drug over 24 h. The bioavailability of F-1 formulation was about 1.8-fold higher than that of standard drug. This enhanced bioavailability of famotidine loaded in microemulsion system might be due to increased intestinal permeability. PMID- 27379273 TI - Detection and Assay of Vitamin B-2 (Riboflavin) in Alkaline Borate Buffer with UV/Visible Spectrophotometry. AB - The detection and assay of vitamin B-2 (riboflavin) was accomplished under aqueous conditions using sodium borate buffering at pH 7.52 conditions. The absorbance spectrum of riboflavin was determined at different pH values utilizing several buffers. The buffer at pH at 7.52 is followed by accurate and sensitive assay of riboflavin by spectrophotometer at 440 nm wavelength. Where indicated an origin solution (stock) was employed by dissolving sufficient vitamin to make a stock solution of 1.403 * 10(-4) molar concentrations. Measurements of various aqueous solutions containing riboflavin were accomplished that included aqueous test samples, vitamin capsules/tablets, and water vitamin mixtures. A standard curve extended from 7.97 * 10(-7) molar to 1.23 * 10(-4) molar (a 154x folds spread in concentration). The equation of the line was y = 12545x (intercept at origin) with Pearson r correlation of 1.000 (R (2) = 1.000). Concentration of riboflavin assayed ranged from 3.00 * 10(-4) gram per liter (0.30 ppm) to 0.0463 gram per liter (46.35 ppm). The B vitamin riboflavin can be assayed by UV/VIS spectrophotometer at 440 nm in aqueous media and using sodium borate buffer at pH 7.52. The assay can reach as low as 0.30 parts per million with high levels of accuracy and sensitivity. PMID- 27379274 TI - Alternans and Spiral Breakup in an Excitable Reaction-Diffusion System: A Simulation Study. AB - The determination of the mechanisms of spiral breakup in excitable media is still an open problem for researchers. In the context of cardiac electrophysiological activities, spiral breakup exhibits complex spatiotemporal pattern known as ventricular fibrillation. The latter is the major cause of sudden cardiac deaths all over the world. In this paper, we numerically study the instability of periodic planar traveling wave solution in two dimensions. The emergence of stable spiral pattern is observed in the considered model. This pattern occurs when the heart is malfunctioning (i.e., ventricular tachycardia). We show that the spiral wave breakup is a consequence of the transverse instability of the planar traveling wave solutions. The alternans, that is, the oscillation of pulse widths, is observed in our simulation results. Moreover, we calculate the widths of spiral pulses numerically and observe that the stable spiral pattern bifurcates to an oscillatory wave pattern in a one-parameter family of solutions. The spiral breakup occurs far below the bifurcation when the maximum and the minimum excited states become more distinct, and hence the alternans becomes more pronounced. PMID- 27379276 TI - Efficient QCA Exclusive-or and Multiplexer Circuits Based on a Nanoelectronic Compatible Designing Approach. AB - Quantum-dot cellular automata (QCA) are a transistorless computation approach which encodes binary information via configuration of charges among quantum dots. The fundamental QCA logic primitives are majority and inverter gates which can be utilized to design various QCA circuits. This study presents a novel approach to designing efficient QCA-based circuits based on Boolean expressions achieved from reconfiguration of five-input and three-input majority gates. Whereas the multiplexer and Exclusive-or are the most important fundamental logical circuits in digital systems, designing efficient and single layer structures without coplanar cross-over wiring is advantageous in QCA technology. In order to demonstrate the efficiency and usefulness of the proposed approach, simple and dense multiplexer and Exclusive-or structures are implemented. The proposed designs have significant improvement in terms of area, complexity, latency, and gate count in comparison to previous designs. The correct logical functionalities of presented structures have been authenticated using QCA designer tool. PMID- 27379275 TI - Osteopontin and Osteoprotegerin as Potential Biomarkers in Abdominal Aortic Aneurysm before and after Treatment. AB - Aim. Although osteopontin (OPN) and osteoprotegerin (OPG) have been associated with abdominal aortic aneurysms (AAAs), no association of these two biomarkers with AAA surgical or endovascular treatment has been reported. Material and Methods. Seventy-four AAA patients were prospectively selected for open or endovascular repair. All aneurysms were classified (Types A-E) according to aneurysmal extent in CT imaging (EUROSTAR criteria). All patients had preoperative serum OPN and OPG values measurements and 1 week after the procedure. Preoperative and postoperative values were compared with a control group of twenty patients (inguinal hernia repair). Results. Preoperative OPN values in patients with any type of aneurysm were higher than in the control group, while OPG values showed no difference. Postoperative OPN values in AAA patients were higher than in the control group. OPN values increased after open surgery and after EVAR. OPG values increased after open surgery but not after EVAR. There was no difference in OPN/OPG values between EVAR and open surgery postoperatively. Conclusions. OPN values are associated with aneurysm presence but not with aneurysm extent. OPG values are not associated either with aneurysm presence or with aneurysm extent. OPN values increase after AAA repair, independently of the type of repair. PMID- 27379278 TI - Some Simple Formulas for Posterior Convergence Rates. AB - We derive some simple relations that demonstrate how the posterior convergence rate is related to two driving factors: a "penalized divergence" of the prior, which measures the ability of the prior distribution to propose a nonnegligible set of working models to approximate the true model and a "norm complexity" of the prior, which measures the complexity of the prior support, weighted by the prior probability masses. These formulas are explicit and involve no essential assumptions and are easy to apply. We apply this approach to the case with model averaging and derive some useful oracle inequalities that can optimize the performance adaptively without knowing the true model. PMID- 27379277 TI - Andrographolide Exerts Chondroprotective Activity in Equine Cartilage Explant and Suppresses Interleukin-1 beta -Induced MMP-2 Expression in Equine Chondrocyte Culture. AB - Cartilage erosion in degenerative joint diseases leads to lameness in affected horses. It has been reported that andrographolide from Andrographis paniculata inhibited cartilage matrix-degrading enzymes. This study aimed to explore whether this compound protects equine cartilage degradation in the explant culture model and to determine its effect on matrix metalloproteinase-2 (MMP-2) expression, a matrix-degrading enzyme, in equine chondrocyte culture. Equine articular cartilage explant culture was induced by 25 ng/mL interleukin-1beta, a key inducer of cartilage degeneration, in cultures with or without andrographolide ranging from 10 to 50 MUM. After 3-21 days, they were analyzed for the markers of cartilage degradation. It was found that interleukin-1beta increased the release of sulfated glycosaminoglycans and hyaluronan from the explants into the culture media consistently with the decrease in uronic acid and collagen content in the cartilage explants. These catabolic effects were inhibited when cotreated with interleukin-1beta and andrographolide. In primary equine chondrocytes, andrographolide suppressed interleukin-1beta-induced MMP-2 mRNA expression and MMP-2 activity in the culture medium. These results confirmed the in vitro potent chondroprotective activities of this compound which were performed in cartilage explants and on a cellular level. These may indicate the application of andrographolide for therapeutic use in equine degenerative joint diseases. PMID- 27379279 TI - Do Glazed Ceramic Pots in a Mexico-US Border City Still Contain Lead? AB - In order to identify the presence of lead in glazed ceramic pots in a Mexico-US border city, 41 clay pots were sampled. The pots were purchased in several establishments located in different geographical areas of the city. The presence of lead was determined using LeadCheck Swabs. Most (58.5%) of the pots were from the State of Jalisco and 24.4% were of unknown origin. Only 4 pots did not contain varnish and were lead-negative. Thirty-seven (81.1%) of the glazed pots were lead positive. Among the lead-negative pots, 4 showed the label "this pot is lead-free." Thus, if we consider the remaining 33 glazed pots without the "Lead Free" label, 90.9% were lead-positive and only 9.1% were lead-negative. We also found that earthenware glazed utensils without the "Lead-Free" label were 1.6 times more likely to contain lead (OR: 1.6, 95% CI 1.0-2.5), P = 0.003. We concluded that lead was detected in almost all acquired food containers. Government interventions in Mexico have focused on training manufacturers to make lead-free glazed ceramics but it has been difficult to eradicate this practice. Educational interventions to make and acquire lead-free glazed ceramics should be targeted to both sellers and buyers. PMID- 27379280 TI - Transfusion-Dependent Anaemia: An Overlooked Complication of Paraoesophageal Hernias. AB - Introduction. A paraoesophageal hernia (PH) may be one reason for iron-deficiency anaemia (IDA) but is often overlooked as a cause. We aimed to assess the incidence and resolution of transfusion-dependent IDA in patients presenting for hiatal hernia surgery. Methods. We analysed a prospective database of patients undergoing laparoscopic hiatal repair in order to identify patients with severe IDA requiring red cell/iron transfusion. Results. Of 138 patients with PH managed over a 4-year period, 7 patients (5.1%; M : F 2 : 5; median age 62 yrs (range 57 82)) with IDA requiring red cell/iron transfusion were identified. Preoperatively, 3/7 patients underwent repetitive and unnecessary diagnostic endoscopic investigations prior to surgery. Only 2/7 ever demonstrated gastric mucosal erosions (Cameron ulcers). All patients were cured from anaemia postoperatively. Discussion. PH is an important differential diagnosis in patients with IDA, even those with marked anaemia and no endoscopically identifiable mucosal lesions. Early recognition can avoid unnecessary additional diagnostic endoscopies. Laparoscopic repair is associated with low morbidity and results in resolution of anaemia. PMID- 27379281 TI - Validation of a Stability-Indicating RP-HPLC Method for Determination of l Carnitine in Tablets. AB - A rapid and stability-indicating RP-HPLC method was developed for determination of l-carnitine in tablets. The separation was based on a C18 analytical column using a mobile phase which consisted of 0.05 M phosphate buffer (pH = 3): ethanol (99 : 1), including 0.56 mg/mL of sodium 1-heptanesulfonate. Column temperature was set at 50 degrees C and quantitation was achieved by UV detection at 225 nm. In forced degradation studies, the drug was subjected to oxidation, hydrolysis, photolysis, and heat. Among the different stress conditions, the exposure to acidic and basic conditions was found to be an important adverse stability factor. The method was validated for specificity, selectivity, linearity, precision, accuracy, and robustness. The applied procedure was found to be linear in l-carnitine concentration range of 84.74-3389.50 ug/mL (r (2) = 0.9997). Precision was evaluated by replicate analysis in which relative standard deviation (RSD) values for areas were found below 2.0%. The recoveries obtained (100.83%-101.54%) ensured the accuracy of the developed method. The expanded uncertainty (3.14%) of the method was also estimated from method validation data. Accordingly, the proposed validated and rapid procedure was proved to be suitable for routine analyzing and stability studies of l-carnitine in tablets. PMID- 27379282 TI - Ion Slip Effect on Viscoelastic Fluid Flow past an Impulsively Started Infinite Vertical Plate Embedded in a Porous Medium with Chemical Reaction. AB - This paper presents the study of convective heat and mass transfer characteristics of an incompressible MHD viscoelastic fluid past an infinite vertical plate immersed in a porous medium with chemical reaction and ion slip effects. Highly nondimensional governing equations are solved analytically by perturbation scheme. The analytical expressions for velocity, shearing stress, temperature, concentration, rate of heat transfer, and mass transfer are obtained. Also, graphical representations have been carried out for velocity field and shearing stress to investigate the effects of viscoelasticity and the effects of ion slip on the fluid flow in combination with other physical parameters involved in the solution. PMID- 27379283 TI - Simple Syntheses of Two New Benzo-Fused Macrocycles Incorporating Chalcone Moiety. AB - Simple syntheses of the benzo-fused 26-membered macrocyclic bischalcone (19E,43E) 2.11.27.36 tetroxaheptacyclo[44.4.0.0(4,9).0(12,17).0(21,26).0(29,34).0(37,42)]pentaconta 1(46),4(9),5,7,12(17),13,15,19,21,23,25,29,31,33,37,39,41,43,47,49-icosaene-18,45 dione (3) and the benzo-fused 13-membered macrocyclic chalcone (19E)-2.11 dioxatetracyclo[19.4.0.0(4,9).0(12,17)]pentacosa 1(25),4(9),5,7,12(17),13,15,19,21,23-decaen-18-one (5) using very common starting materials and reagents are described. The compounds are new and they have been characterized from their analytical and spectral data. PMID- 27379284 TI - Development and Validation of an Affinity Chromatography-Protein G Method for IgG Quantification. AB - Nimotuzumab, an IgG that recognizes the epidermal growth factor receptor (EGF-R) overexpressed in some tumors, is used in the treatment of advanced head and neck cancer. For the quantification of this protein in cell culture supernatants, protein G-HPLC affinity chromatography is used due to its high affinity and specificity for antibodies of this class. The technique relies on the comparison of the area under the curve of the elution peak of the samples to be evaluated versus to a calibration curve of well-known concentrations and was validated by assessment of its robustness, specificity, repeatability, intermediate precision, accuracy, linearity, limit of detection, limit of quantification, and range. According to results of the study all validation parameters fulfilled the preestablished acceptance criteria and demonstrated the feasibility of the assay for the analysis of samples of cell culture supernatant as well as drug product. PMID- 27379285 TI - Effect of Hygrothermal Aging on the Mechanical Properties of Fluorinated and Nonfluorinated Clay-Epoxy Nanocomposites. AB - Hydrophilic nature of epoxy polymers can lead to both reversible and irreversible/permanent changes in epoxy upon moisture absorption. The permanent changes leading to the degradation of mechanical properties due to combined effect of moisture and elevated temperature on EPON 862, Nanomer I.28E, and Somasif MAE clay-epoxy nanocomposites are investigated in this study. The extent of permanent degradation on fracture and flexural properties due to the hygrothermal aging is determined by drying the epoxy and their clay-epoxy nanocomposites after moisture absorption. Significant permanent damage is observed for fracture toughness and flexural modulus, while the extent of permanent damage is less significant for flexural strength. It is also observed that permanent degradation in Somasif MAE clay-epoxy nanocomposites is higher compared to Nanomer I.28E clay-epoxy nanocomposites. Fourier transform infrared (FTIR) spectroscopy revealed that both clays retained their original chemical structure after the absorption-desorption cycle without undergoing significant changes. Scanning electron microscopy (SEM) images of the fracture surfaces provide evidence that Somasif MAE clay particles offered very little resistance to crack propagation in case of redried specimens when compared to Nanomer I.28E counterpart. The reason for the observed higher extent of permanent degradation in Somasif MAE clay-epoxy system has been attributed to the weakening of the filler-matrix interface. PMID- 27379286 TI - In Vitro Antimycobacterial Activity of Pakistani Beri Honey Using BACTEC MGIT 960. AB - Background. Tuberculosis (TB) is a chronic bacterial disease. Mycobacterium tuberculosis, being the leading member of the MTB complex, is the main cause of tuberculosis worldwide. Tuberculosis is managed with combination of drugs: streptomycin, isoniazid, rifampicin, ethambutol, and pyrazinamide. Over the recent past years resistance against first line antituberculous drugs has emerged rapidly throughout the world resulting in MDR strains. The new threat in the management of MDR-TB is the development of resistance against second line drugs: aminoglycosides, polypeptides, fluoroquinolones, and thioamides. Multidrug resistant (MDR) and extensively drug resistant TB (XDR) strains have become a major concern to control TB particularly in the developing countries. The need of the hour is to look for new modalities having antimycobacterial activity. Honey has been well known for its antibacterial activity. We intended to explore its antimycobacterial activity against MDR-TB. Objective. The objective of this study was to determine whether Pakistani Beri honey has any antimycobacterial activity. Method. The study was conducted in the Department of Microbiology, University of Health Sciences, Lahore. Clinical isolates (n = 21) of MDR-MTB were evaluated for their susceptibility to Beri honey. The isolates were provided, courtesy of Pakistan Medical Research Council. These isolates were identified by MTBc ID test (Becton & Dickinson) and further tested for their antimycobacterial activity using Beri honey. The honey was tested at the following concentrations (v/v): 1%, 2%, 3%, 4%, and 5% in MGIT 960. Growth controls were also inoculated with each isolate (growth control has no concentration of honey, only containing growth of isolate). Results. MDR-TB isolates (n = 21) were tested; 3 (14%) isolates were susceptible at 1% v/v honey, while at 2% v/v of honey 18 (86%) isolates were found to be susceptible. All the 21 isolates (n = 21) were susceptible at 3% v/v of honey. Conclusion. The present study clearly demonstrates that Pakistani Beri honey possesses significant antimycobacterial activity in vitro. The antimycobacterial activity of Pakistani Beri honey may, therefore, be exploited in an appropriate mouse model. PMID- 27379287 TI - Synthesis, Characterization, and In Vitro Antimicrobial and Anticancer Evaluation of Copolyester Bearing 4-Arylidene Curcumin in the Main Chain. AB - Synthesis of random copolyester bearing 4-arylidene curcumin M 1 in the polymer backbone was prepared by solution polycondensation method. The influence of copolyester bearing 4-arylidene curcumin M 1 unit on the properties of copolyester such as inherent viscosity, solubility, and thermal stability was investigated and studied in detail. The inherent viscosity and polydispersity index of the copolyester were found to be 0.19 dL/g and 1.38, respectively. The chemical structure of the copolyester was investigated by Fourier-transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance ((1)H-NMR) spectroscopy. The physical properties of copolyester were characterized by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), gel permeation chromatography (GPC), and X-ray diffraction (XRD) technique. Agar disc diffusion method was employed to study the antimicrobial activity of the random copolyester. In vitro anticancer activity against lung cancer (Hep-2) cell line was investigated. PMID- 27379288 TI - Tillage Effects on Selected Soil Physical Properties in a Maize-Bean Intercropping System in Mwala District, Kenya. AB - A field study was carried out to evaluate the effects of tillage practices on soil physical properties in Mwala district, Eastern Kenya, during the long rains (LR) and short rains (SR) of 2012/13. The treatments were disc ploughing (DP), disc ploughing and harrowing (DPH), ox-ploughing (OX), subsoiling-ripping (SSR), hand hoeing with tied ridges (HTR), hand hoeing only (H). These were investigated under three cropping systems of sole maize, sole bean, and maize-bean intercrop in a split-plot design with four replications. Soil physical properties were monitored at different weeks after planting (WAP) throughout the growing seasons. A four-season average shows that soil moisture content was significantly (P < 0.05) higher in OX > SSR > DPH > H > HTR > DP with values ranging from 13.1 to 14.1%. Soil surface roughness and crust strength varied significantly (P < 0.05) over time within the growing seasons, between the tillage practices, and across the different seasons with values ranging from 26 to 66% and 1.21 to 1.31 MPa, respectively. Tillage practices and cropping systems did not significantly affect bulk density, porosity, or K sat values. It is apparent that long term tillage experiment (>4 seasons) would be required to detect changes in soil physical properties as a result of the soil management practices. PMID- 27379289 TI - Status of Day Care Laparoscopic Appendectomy in Developing Countries. AB - The practice of laparoscopic appendectomy as an ambulatory surgery is uncommon even in apex institutes, more so in developing countries, despite proven feasibility. To promote this practice in the developing countries like ours, we attempted to find the safety and cost effectiveness in such institutions which have limited resources. Thirty cases of symptomatic appendicitis were tried for same day discharge after laparoscopic appendectomies. The results were encouraging with 87% patients discharged on the same day and 13% on the next day in the early morning. Among the next day discharged cases, only 03% stayed for medical reasons (nausea, vomiting, and pain) while 10% stayed as their attendants declined to leave (social reasons), even though they were medically eligible for discharge from the hospital. There were no significant postoperative complications except tolerable pain in all patients and mild to moderate nausea/vomiting in 80%. There was no readmission. The mean length of hospital stay was 11.20 hrs. At the time of discharge all patients were highly satisfied. We concluded that routine same day discharge is safe and feasible after appendectomies in developing countries, with social decline as the main hurdle which can be improved by proper communication. PMID- 27379290 TI - Taste Masked Orally Disintegrating Pellets of Antihistaminic and Mucolytic Drug: Formulation, Characterization, and In Vivo Studies in Human. AB - The main aim of the present study was to evaluate the potential of orally disintegrating pellets (ODPs) as an approach for taste masking of bitter drugs, namely, Ambroxol hydrochloride (A-HCl) and Cetirizine dihydrochloride (C-DHCl). Pellets were prepared by extrusion/spheronization with Eudragit EPO, kyron T-134, Kyron T-314, mannitol, sorbitol, MCC (Avicel PH-101), sucralose, chocolate flavor, and 5% xanthum gum. The prepared pellets were characterized for percentage yield, drug content, particle size, in vitro drug release, and in vivo evaluation on humans for taste, mouth feel, and in vivo disintegration time. The results revealed that the average size of pellets was influenced greatly by the percentage of binder and extrusion speed. The optimized ODPs disintegrated in less than 20 s and showed more than 98% of drugs in ODPs dissolved within 15 min. Taste perception study was carried out on human volunteers to evaluate the taste masking ability of ODPs for taste, mouth feel, and in vivo disintegration time. Crystalline state evaluation of drugs in the optimized ODPs was conducted for X ray powder diffraction. In conclusion, the study confirmed that ODPs can be utilized as an alternative approach for effective taste masking and rapid disintegration in the oral cavity. PMID- 27379291 TI - Determinants of Physical Health of Older People in Iran. AB - Background. Many of the older people are encountered with physical and mental health problems, chronic diseases, and also living conditions. We aimed to evaluate the disability scores and its associated factors among a sample of older people in Iran. Material and Methods. 330 people aged 60-70 years were interviewed about daily living activities and physical functioning using two standard questionnaires. Results. According to univariate analysis, aging 66-70 years, being employed, and receiving financial aids were associated with better ADL mean score (P < 0.05). Also, being between 66 and 70 years of age, males, being illiterate, being employed, and receiving financial aids were statistically related to higher SF-36 mean scores (P < 0.05). Multivariate analyses have shown that higher age and receiving financial aids were related to less need for help and being unemployed with salary was related to higher need for help. However, being illiterate, being employed, and receiving financial aids were significant related factors for better physical functioning. Conclusions. Physical health in old people is decreased not only by aging of people but also by other factors such as financial problems and also employment status could decrease physical health of old people regardless of aging. PMID- 27379292 TI - Bayesian Inference for Source Reconstruction: A Real-World Application. AB - This paper applies a Bayesian probabilistic inferential methodology for the reconstruction of the location and emission rate from an actual contaminant source (emission from the Chalk River Laboratories medical isotope production facility) using a small number of activity concentration measurements of a noble gas (Xenon-133) obtained from three stations that form part of the International Monitoring System radionuclide network. The sampling of the resulting posterior distribution of the source parameters is undertaken using a very efficient Markov chain Monte Carlo technique that utilizes a multiple-try differential evolution adaptive Metropolis algorithm with an archive of past states. It is shown that the principal difficulty in the reconstruction lay in the correct specification of the model errors (both scale and structure) for use in the Bayesian inferential methodology. In this context, two different measurement models for incorporation of the model error of the predicted concentrations are considered. The performance of both of these measurement models with respect to their accuracy and precision in the recovery of the source parameters is compared and contrasted. PMID- 27379293 TI - The Effect of Interventional Program on Breastfeeding Self-Efficacy and Duration of Exclusive Breastfeeding in Pregnant Women in Ahvaz, Iran. AB - Objective. This study aimed to determine the effect of educational program on Breastfeeding self-efficacy and duration of exclusive breastfeeding in pregnant women in Ahvaz, Iran. Methods. This randomized controlled trial was conducted on 120 nulliparous pregnant women who tended to breastfeed. The primary self efficacy scores of samples were measured using Faux and Dennis breastfeeding self efficacy questionnaire. Women were randomly recruited into two intervention and control groups. Educational program (two training sessions, each lasted two hours) with two days interval was performed for intervention group. One month after delivery, self-efficacy scores were determined. Six months after child birth, duration of exclusive breastfeeding was assessed. Data were analyzed by means of descriptive and inferential statistics. Findings. The breastfeeding self efficacy in the intervention group increased significantly compared to the control group one month after delivery (123.6 versus 101.7, P < 0.001). The duration of exclusive breastfeeding was significantly higher in the intervention group (5.03 mo versus 2.7 mo, P < 0.001). Also, there was a significant relationship between breastfeeding self-efficacy and duration of exclusive breastfeeding (P < 0.001). Conclusion. The educational program could increase the self-efficacy and exclusive breastfeeding duration of mothers. These results can draw the attention of authorities to the importance of educational programs for mothers regarding the exclusive breastfeeding. PMID- 27379294 TI - Occlusal Characteristics and Spacing in Primary Dentition: A Gender Comparative Cross-Sectional Study. AB - Context. Occlusion in primary teeth varies among children of different populations and races. Aim. To assess and compare the occlusal characteristics and spacing in primary dentition among 3-6-year-old Dravidian children. Materials and Methods. The study included 2281 school going children. The primary molar relation, canine relation, overjet, and overbite were assessed using Foster and Hamilton criteria. Spacing conditions were registered according to Kisling and Krebs criteria. Results. The flush terminal plane molar relation (80.3%) was the most common primary molar relation. The distal step molar relation was more frequently found in female children (12.8%) than in males (8.6%). Class 1 canine relation was the most prevalent canine relation (81.3%) among males and females. Ideal overjet (84.3%) and overbite (72.7%) were observed among the majority of the children. Spaced type of arches occurred more frequently than closed arches in this sample. The incidence of primate spaces was more in males than in females. Conclusion. The study population has fewer deviations from normal occlusion which indicates decreased tendency for malocclusion in permanent dentition. However, further longitudinal studies are necessary to identify the potential limitations of a clinical approach relying on early orthodontic diagnosis and intervention. PMID- 27379295 TI - Studies on Oligomer Metal Complexes Derived from Bisamic Acid of Pyromellitic Dianhydride and 4-Bromoaniline. AB - Novel oligomer metal complexes (2a-f) of the ligand 2,5-bis((4 bromophenyl)carbamoyl) terephthalic acid (1) were prepared using transition metal salts and characterized by various spectroscopic techniques. The geometry of oligomer metal complexes was carried out by electronic spectral analysis and magnetic measurement studies. Polymeric properties have also been carried out. Ligand was synthesized using pyromellitic dianhydride and 4-bromoaniline. It was duly characterized. All novel synthesized compounds 1 and 2a-f were evaluated for their antibacterial and antifungal activity. The results showed significantly higher antibacterial and antifungal activity of oligomer metal complexes compared to the ligand. PMID- 27379296 TI - Nitrite as Direct S-Nitrosylating Agent of Kir2.1 Channels. AB - Nitrite, a physiological nitric oxide (NO) storage form and an alternative way for NO generation, affects numerous biological processes through NO-dependent and independent pathways, including the S-nitrosylation of thiol-containing proteins. Mechanisms underlying these phenomena are not fully understood. The purpose of this study was to analyse in the rat heart (as prototype of mammalian heart) whether nitrite affects S-nitrosylation of cardiac proteins and the potential targets for S-nitrosylation. Rat hearts, perfused according to Langendorff, were exposed to nitrite. By Biotin Switch Method, we showed that nitrite treatment increased the degree of S-nitrosylation of a broad range of membrane proteins. Further analysis, conducted on subfractioned proteins, allowed us to identify a high level of nitrosylation in a small range of plasmalemmal proteins characterized by using an anti-Kir2.1 rabbit polyclonal antibody. We also verified that this effect of nitrite is preserved in the presence of the NO scavenger PTIO (2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide). Our results suggest, for the first time, that nitrite represents a direct S nitrosylating agent in cardiac tissues and that inward-rectifier potassium ion channels (Kir2.1) are one of the targets. These observations are of relevance since they support the growing evidence that nitrite is not only a NO reserve but also a direct modulator of important functional cardiac proteins. PMID- 27379297 TI - Occupational and Personal Determinants of Musculoskeletal Disorders among Urban Taxi Drivers in Ghana. AB - Background. There is a lack of epidemiological data on musculoskeletal disorders (MSDs) among occupational drivers in Ghana. The present study seeks to estimate the prevalence, body distribution, and occupational and personal determinants of MSDs in a sample of taxi drivers in the Accra Metropolis of Ghana. Methods. A total of 210 participants were enrolled in this cross-sectional study. All the participants were evaluated by using a semistructured questionnaire and the standardized Nordic Musculoskeletal Disorder Questionnaire. Results. The estimated prevalence of MSDs was 70.5%. The prevalence of the various MSD domains was as follows: lower back pain (34.3%), upper back pain (16.7%), neck pain (15.2%), shoulder pain (11.0%), knee pain (10.0%), hip/thigh pain (2.9%), elbow pain (4.8%), ankle/feet pain (2.4%), and wrist/hand pain (1.9%). Multiple logistic regression analysis of the data showed that participants who were employee drivers, drove taxi more than 12 hours per day or at least 5 days per week, perceived their job as stressful, and were dissatisfied with their job were at a greater risk of developing MSDs. Conclusions. These findings call for preventive strategies and safety guidelines in order to reduce the incidence of MSDs among urban taxi drivers in Ghana. PMID- 27379298 TI - Experimental Study on the Strength Characteristics and Water Permeability of Hybrid Steel Fibre Reinforced Concrete. AB - Results of an investigation conducted to study the effect of fibre hybridization on the strength characteristics such as compressive strength, split tensile strength, and water permeability of steel fibre reinforced concrete (SFRC) are presented. Steel fibres of different lengths, that is, 12.5 mm, 25 mm, and 50 mm, having constant diameter of 0.6 mm, were systematically combined in different mix proportions to obtain mono, binary, and ternary combinations at each of 0.5%, 1.0%, and 1.5% fibre volume fraction. A concrete mix containing no fibres was also cast for reference purpose. A total number of 1440 cube specimens of size 100*100*100 mm were tested, 480 each for compressive strength, split tensile strength, and water permeability at 7, 28, 90, and 120 days of curing. It has been observed from the results of this investigation that a fibre combination of 33% 12.5 mm + 33% 25 mm + 33% 50 mm long fibres can be adjudged as the most appropriate combination to be employed in hybrid steel fibre reinforced concrete (HySFRC) for optimum performance in terms of compressive strength, split tensile strength and water permeability requirements taken together. PMID- 27379300 TI - A Comparative Study between Karydakis Flap Reconstruction and Double Z-Plasty in Patients with Sacrococcygeal Pilonidal Disease. AB - The most difficult problems that follow surgery for pilonidal disease are persistent unhealed midline wound and recurrence. Various innovations were proposed to deal with these problems. The adipocutaneous flap of Karydakis was devised to shift the natal cleft, while Z-plasty involves fasciocutaneous flap. The present prospective randomized trial was conducted on 50 cases of symptomatic or recurrent pilonidal sinuses divided randomly into two equal groups undergoing Karydakis procedure and Z-plasty. The duration of hospitalization for Karydakis procedure was found significantly lesser than that for double Z-plasty (P < 0.001). Similar observations are obtained for duration of wound healing (P < 0.001), work off period (P < 0.001), and the duration of presence of significant pain postoperatively (P < 0.001). The overall complications were more in double Z plasty. Recurrence developed in 32% of the cases in double Z-plasty group comparable to no recurrence seen in Karydakis procedure. Thus, Karydakis flap was found superior to double Z-plasty having less seroma formation, no local hematoma, and no flap necrosis. Statistically, this comparison was highly significant (P < 0.001). Karydakis flap has some added advantages over double Z plasty technique like keeping scar away from the midline and flattening of the natal cleft, thus reducing local recurrence rates. PMID- 27379299 TI - Protective Effects of Tualang Honey against Oxidative Stress and Anxiety-Like Behaviour in Stressed Ovariectomized Rats. AB - The present study aims to evaluate the antioxidant and anxiolytic-like effect of Tualang honey in stressed ovariectomized (OVX) rats. The animals were divided into; (i) nonstressed sham-operated control rats, (ii) sham-operated control rats exposed to stress, (iii) nonstressed OVX rats, (iv) OVX rats exposed to stress, (v) OVX rats exposed to stress and treated with 17 beta-oestradiol (E2) (20 MUg daily, sc), and (vi) OVX rats exposed to stress and treated with Tualang honey (0.2 g/kg body weight, orally). The open field test was used to evaluate the anxiety-like behaviour and ELISA kits were used to measure oxidant/antioxidant status of the brain homogenates. The result showed that anxiety-like behavior was significantly increased in stressed OVX compared to other groups, and administering either E2 or Tualang honey significantly decreased anxiety-like behaviour in stressed OVX rats. The levels of malondialdehyde (MDA) and protein carbonyl (PCO) were significantly decreased while the levels/activities of superoxide dismutase (SOD), glutathione S-transferases (GST), glutathione peroxidase (GPx), and glutathione reductase (GR) were significantly increased in the brain homogenates of treated stressed OVX groups compared to untreated stressed OVX. In conclusion, Tualang honey has protective effects against brain oxidative stress and may be useful alternative anxiolytic agent especially for postmenopausal women. PMID- 27379301 TI - Giardia duodenalis: Number and Fluorescence Reduction Caused by the Advanced Oxidation Process (H2O2/UV). AB - This study evaluated the effect of peroxidation assisted by ultraviolet radiation (H2O2/UV), which is an advanced oxidation process (AOP), on Giardia duodenalis cysts. The cysts were inoculated in synthetic and surface water using a concentration of 12 g H2O2 L(-1) and a UV dose (lambda = 254 nm) of 5,480 mJcm( 2). The aqueous solutions were concentrated using membrane filtration, and the organisms were observed using a direct immunofluorescence assay (IFA). The AOP was effective in reducing the number of G. duodenalis cysts in synthetic and surface water and was most effective in reducing the fluorescence of the cyst walls that were present in the surface water. The AOP showed a higher deleterious potential for G. duodenalis cysts than either peroxidation (H2O2) or photolysis (UV) processes alone. PMID- 27379302 TI - Barriers to and Suggestions on Improving Utilization of Eye Care in High-Risk Individuals: Focus Group Results. AB - Purpose. To understand barriers facing high-risk individuals and to solicit the suggestions of these individuals, especially nonusers, on how to change the eye care delivery system to better meet their needs. Methods. Four focus groups were conducted. All discussion was audiotaped and transcribed. Content analysis was performed by the authors and with the assistance of qualitative software, NUD(*)IST Vivo. Results. The most frequently cited barriers include (1) cost, (2) trust, (3) communication, (4) clinic accessibility (transportation/distance), and (5) doctor-patient relationship. In underutilizers, trust was the most identified barrier to care. Suggestions on increasing educational opportunities/awareness of eye care and addressing cost and insurance issues as a means of improving trust and communications were most frequently offered, including using the Department of Social Services as a focal point for eye care education and assessment. Discussion. Trust is a major barrier to eye care, especially among underutilizers of disadvantaged populations. Increasing trust and eye care education at the community and individual levels is essential to increasing eye care utilization. PMID- 27379303 TI - On Critical Buckling Loads of Columns under End Load Dependent on Direction. AB - Most of the phenomena of various fields of applied sciences are nonlinear problems. Recently, various types of analytical approximate solution techniques were introduced and successfully applied to the nonlinear differential equations. One of the aforementioned techniques is the Homotopy analysis method (HAM). In this study, we applied HAM to find critical buckling load of a column under end load dependent on direction. We obtained the critical buckling loads and compared them with the exact analytic solutions in the literature. PMID- 27379304 TI - Existence and Uniqueness of Positive Solution for Discrete Multipoint Boundary Value Problems. AB - It is expected in this paper to investigate the existence and uniqueness of positive solution for the following difference equation: -Delta(2) u(t - 1) = f(t, u(t)) + g(t, u(t)), t ? Z 1, T , subject to boundary conditions either u(0) - betaDeltau(0) = 0, u(T + 1) = alphau(eta) or Deltau(0) = 0, u(T + 1) = alphau(eta), where 0 < alpha < 1, beta > 0, and eta ? Z 2,T-1. The proof of the main result is based upon a fixed point theorem of a sum operator. It is expected in this paper not only to establish existence and uniqueness of positive solution, but also to show a way to construct a series to approximate it by iteration. PMID- 27379306 TI - Comparing in Cylinder Pressure Modelling of a DI Diesel Engine Fuelled on Alternative Fuel Using Two Tabulated Chemistry Approaches. AB - The present work presents the comparative simulation of a diesel engine fuelled on diesel fuel and biodiesel fuel. Two models, based on tabulated chemistry, were implemented for the simulation purpose and results were compared with experimental data obtained from a single cylinder diesel engine. The first model is a single zone model based on the Krieger and Bormann combustion model while the second model is a two-zone model based on Olikara and Bormann combustion model. It was shown that both models can predict well the engine's in-cylinder pressure as well as its overall performances. The second model showed a better accuracy than the first, while the first model was easier to implement and faster to compute. It was found that the first method was better suited for real time engine control and monitoring while the second one was better suited for engine design and emission prediction. PMID- 27379307 TI - Growth Analysis of Composite Entire and Meromorphic Functions in the Light of Their Relative Orders. AB - We study some comparative growth properties of composite entire and meromorphic functions on the basis of their relative orders (relative lower orders). PMID- 27379305 TI - Current Trends in Bioethanol Production by Saccharomyces cerevisiae: Substrate, Inhibitor Reduction, Growth Variables, Coculture, and Immobilization. AB - Bioethanol is one of the most commonly used biofuels in transportation sector to reduce greenhouse gases. S. cerevisiae is the most employed yeast for ethanol production at industrial level though ethanol is produced by an array of other yeasts, bacteria, and fungi. This paper reviews the current and nonmolecular trends in ethanol production using S. cerevisiae. Ethanol has been produced from wide range of substrates such as molasses, starch based substrate, sweet sorghum cane extract, lignocellulose, and other wastes. The inhibitors in lignocellulosic hydrolysates can be reduced by repeated sequential fermentation, treatment with reducing agents and activated charcoal, overliming, anion exchanger, evaporation, enzymatic treatment with peroxidase and laccase, in situ detoxification by fermenting microbes, and different extraction methods. Coculturing S. cerevisiae with other yeasts or microbes is targeted to optimize ethanol production, shorten fermentation time, and reduce process cost. Immobilization of yeast cells has been considered as potential alternative for enhancing ethanol productivity, because immobilizing yeasts reduce risk of contamination, make the separation of cell mass from the bulk liquid easy, retain stability of cell activities, minimize production costs, enable biocatalyst recycling, reduce fermentation time, and protect the cells from inhibitors. The effects of growth variables of the yeast and supplementation of external nitrogen sources on ethanol optimization are also reviewed. PMID- 27379308 TI - Second Order Duality in Multiobjective Fractional Programming with Square Root Term under Generalized Univex Function. AB - Three approaches of second order mixed type duality are introduced for a nondifferentiable multiobjective fractional programming problem in which the numerator and denominator of objective function contain square root of positive semidefinite quadratic form. Also, the necessary and sufficient conditions of efficient solution for fractional programming are established and a parameterization technique is used to establish duality results under generalized second order rho-univexity assumption. PMID- 27379309 TI - Simultaneous Spectrophotometric Method for Determination of Emtricitabine and Tenofovir Disoproxil Fumarate in Three-Component Tablet Formulation Containing Rilpivirine Hydrochloride. AB - Developing a single analytical method for estimation of individual drug from a multidrug composition is a very challenging task. A complexation, derivatization, extraction, evaporation, and sensitive-free direct UV spectrophotometric method is developed and validated for the simultaneous estimation of some antiviral drugs such as emtricitabine (EMT), tenofovir disoproxil fumarate (TDF), and rilpivirine HCl (RPV) in tablet dosage form by Vierordt's method. The solutions of standard and sample were prepared in methanol. The lambda max? for emtricitabine, tenofovir disoproxil fumarate, and rilpivirine hydrochloride were 240.8 nm, 257.6 nm, and 305.6 nm, respectively. Calibration curves are linear in the concentration ranges 4-12 MUg/ml for EMT, 6-18 MUg/ml for TDF, and 0.5-1.5 MUg/ml for RPV, respectively. Results of analysis of simultaneous equation method were analyzed and validated for various parameters according to ICH guidelines. PMID- 27379310 TI - A Low-Dimensional Radial Silhouette-Based Feature for Fast Human Action Recognition Fusing Multiple Views. AB - This paper presents a novel silhouette-based feature for vision-based human action recognition, which relies on the contour of the silhouette and a radial scheme. Its low-dimensionality and ease of extraction result in an outstanding proficiency for real-time scenarios. This feature is used in a learning algorithm that by means of model fusion of multiple camera streams builds a bag of key poses, which serves as a dictionary of known poses and allows converting the training sequences into sequences of key poses. These are used in order to perform action recognition by means of a sequence matching algorithm. Experimentation on three different datasets returns high and stable recognition rates. To the best of our knowledge, this paper presents the highest results so far on the MuHAVi-MAS dataset. Real-time suitability is given, since the method easily performs above video frequency. Therefore, the related requirements that applications as ambient-assisted living services impose are successfully fulfilled. PMID- 27379311 TI - Two-Sided Annihilator Condition with Generalized Derivations on Multilinear Polynomials. AB - Let R be a prime ring of characteristic different from 2, with extended centroid C, U its two-sided Utumi quotient ring, F a nonzero generalized derivation of R, f(x 1,..., x n ) a noncentral multilinear polynomial over C in n noncommuting variables, and a, b ? R such that a[F(f(r 1,..., r n )), f(r 1,..., r n )]b = 0 for any r 1,..., r n ? R. Then one of the following holds: (1) a = 0; (2) b = 0; (3) there exists lambda ? C such that F(x) = lambdax, for all x ? R; (4) there exist q ? U and lambda ? C such that F(x) = (q + lambda)x + xq, for all x ? R, and f(x 1,..., x n )(2) is central valued on R; (5) there exist q ? U and lambda, MU ? C such that F(x) = (q + lambda)x + xq, for all x ? R, and aq = MUa, qb = MUb. PMID- 27379312 TI - Occurrence of Enterobacteriaceae in Raw Meat and in Human Samples from Egyptian Retail Sellers. AB - The present study was performed to assess the presence of Enterobacteriaceae in raw meat and handlers in Egypt using cultivation and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). A total of 100 raw meat samples (chicken and beef meat, 50 each) were randomly purchased from butchers and local meat retailers located at Mansoura city, Egypt. Fifty human samples were collected from meat handlers (hand swabs and stool specimens, 25 each). 228 bacterial isolates were recovered from these samples. Unidentified isolates were characterized by partial 16S rRNA gene sequencing. Escherichia coli isolates were further typed using a DNA microarray system. Proteus spp. (60.0%) were found to be the most abundant followed by Escherichia coli (38.7%), Klebsiella spp. (17.3%), and Citrobacter spp. (13.3%). The presence of different Enterobacteriaceae in locally produced retail raw meat demonstrates the risk of infection of people through consumption of raw or undercooked meat and the risk for cross-contamination of other food products. Harmonized and concerted actions from veterinary and public health authorities are needed to reduce the risk of infection. PMID- 27379313 TI - Outcomes of Robot-Assisted Laparoscopic Prostatectomy with a Posterior Approach to the Seminal Vesicle in 300 Patients. AB - Background. The goal of this study was to analyze the perioperative outcomes of robot-assisted laparoscopic radical prostatectomies (RALPs) performed at our center. Methodology. We retrospectively reviewed 300 consecutive patients with clinically localized prostate cancer who underwent RALP with a posterior dissection approach to the seminal vesicle between May 2011 and November 2013. The mean patient age was 67.2 +/- 5.5 years (range: 41-78 years), and the mean prostate-specific antigen (PSA) concentration, at diagnosis of prostate cancer, was 9.16 +/- 6.50 ng/mL (range: 2.20-55.31 ng/mL). Results. The median duration of robotic surgery was 160 min (mean: 165 +/- 40 min; range: 75-345 min). Median estimated blood loss, including that in urine, was 200 mL (mean: 277 +/- 324 mL; range: 4-3250 mL). Intraoperative and immediate postoperative complications occurred in 3.0% of patients; 4 patients required allogeneic blood transfusion. As a measure of patient continence, 82.4% did not use more than 1 absorbent pad in 24 h, at 6 months postoperatively. Conclusion. RALP with an initial posterior dissection to the seminal vesicle was a safe and efficient method for controlling prostate cancer, even in these initial cases. PMID- 27379314 TI - Phytochemical Profiling of Leaf, Stem, and Tuber Parts of Solena amplexicaulis (Lam.) Gandhi Using GC-MS. AB - Objective. To explore the possible bioactive compounds in the methanolic extracts of leaf, stem, and tuber parts of the medicinal climber, Solena amplexicaulis, using GC-MS. Methods. GC-MS analysis of the plant extracts were performed by using GC-MS-5975C [Agilent] and mass spectra of the compounds found in the extract was matched with the data in the library of National Institute of Standards and Technology (NIST). Results. Thirty-five compounds were determined to be present in the parts studied. The active principles with their retention time, molecular formula, molecular weight, peak area, structure, category of the compounds, and activities were predicted. The most prevailing compounds were phytol (38.24%) in leaf, 4-(4-ethoxyphenyl) but-3-en-2-one (56.90%) in stem, and 9,17-octadecadienal, (Z)- (21.77%) in tuber. Conclusion. This study revealed that the species S. amplexicaulis is a good source of many bioactive compounds like terpenes, triazines, esters, alkanes, alcohols, hydrocarbons, aldehydes, amides, and so forth. That justifies the traditional usage of this species. PMID- 27379315 TI - Influence of Sulfur Induced Stress on Oxidative Status and Antioxidative Machinery in Leaves of Allium cepa L. AB - A pot culture experiment was carried out to assess the effect of sulfur stress on growth, oxidative status, and antioxidative metabolism. Onion plants were treated with three different levels of sulfur, namely, 1.0, 4.0, and 8.0 mM S L(-1). Plants raised with 4.0 mM S L(-1) represent sufficient growth for the best vegetative yield. Plants supplied with 1.0 and 8.0 mM S L(-1) showed retarded growth, chlorosis, and reduction in biomass and photoassimilatory pigments. Tissue sulfur concentration and cysteine were increased with increasing sulfur supply. Carbohydrates (sugars and starch) were accumulated in sulfur stressed plants. Hydrogen peroxide levels were increased in sulfur stressed plants. Thiobarbituric acid reactive substances levels were also increased which was an indicator of lipid peroxidation. Enzymatic (superoxide dismutase, catalase, peroxidase, ascorbate peroxidase, and glutathione reductase) and nonenzymatic (asorbate) antioxidative components were enhanced in sulfur stressed plants. Glutathione was increased with increasing sulfur supply. The present study showed that the adverse effects of inadequate sulfur supply result in irregular metabolic activities and antioxidant machinery. PMID- 27379316 TI - Heat and Mass Transfer on MHD Flow of a Viscoelastic Fluid through Porous Media over a Shrinking Sheet. AB - An attempt has been made to study the heat and mass transfer effect in a boundary layer flow through porous medium of an electrically conducting viscoelastic fluid over a shrinking sheet subject to transverse magnetic field in the presence of heat source. Effects of radiation, viscous dissipation, and uniform heat sink on the heat transfer have been considered. The method of solution involves similarity transformation. The coupled nonlinear partial differential equations representing momentum, concentration, and nonhomogenous heat equation are reduced into a set of nonlinear ordinary differential equations. The transformed equations are solved by applying Kummer's function. The exact solution of temperature field is obtained for power-law surface temperature (PST) as well as power-law heat flux (PHF) boundary condition. The interaction of magnetic field is proved to be counterproductive in enhancing velocity and concentration distribution, whereas presence of porous matrix reduces the temperature field at all points. PMID- 27379317 TI - Comparison of the Antifungal Efficacy of 1.3% NaOCl/MTAD with Other Routine Irrigants: An Ex-Vivo Study. AB - Objectives. To evaluate and compare the antifungal efficacy of 1.3% NaOCl/MTAD with 2.5% sodium hypochlorite (NaOCl), 2% chlorhexidine gluconate (CHX), and iodine potassium iodide (IKI). Materials and Methods. Fifty-two single rooted teeth were used which were divided into four groups with 10 teeth in each group: 2.5% NaOCl, 2% CHX, IKI, 1.3% NaOCl/MTAD, and physiologic saline. Two teeth served as negative controls and were placed in fresh brain-heart infusion broth (BHI) after autoclaving. The teeth were inoculated and incubated with Candida albicans after which the teeth were instrumented and irrigated with the test irrigants. The first microbial sampling was then performed and colony forming unit/mL (cfu/mL) was counted. The second microbial sampling was performed 1 week after instrumentation and irrigation. Results. The test irrigants were effective against C. albicans in both the first and second microbial samplings. When the irrigants were compared, there was no statistical difference in their activity in the 1st and 2nd microbial sampling. On comparison of the change in mean cfu/mL between the 1st and 2nd microbial samplings, the antifungal activity of the test irrigants was in the order 2.5% NaOCl > 2% CHX > 1.3% NaOCl/MTAD > IKI. PMID- 27379318 TI - A Real Valued Neural Network Based Autoregressive Energy Detector for Cognitive Radio Application. AB - A real valued neural network (RVNN) based energy detector (ED) is proposed and analyzed for cognitive radio (CR) application. This was developed using a known two-layered RVNN model to estimate the model coefficients of an autoregressive (AR) system. By using appropriate modules and a well-designed detector, the power spectral density (PSD) of the AR system transfer function was estimated and subsequent receiver operating characteristic (ROC) curves of the detector generated and analyzed. A high detection performance with low false alarm rate was observed for varying signal to noise ratio (SNR), sample number, and model order conditions. The proposed RVNN based ED was then compared to the simple periodogram (SP), Welch periodogram (WP), multitaper (MT), Yule-Walker (YW), Burg (BG), and covariance (CV) based ED techniques. The proposed detector showed better performance than the SP, WP, and MT while providing better false alarm performance than the YW, BG, and CV. Data provided here support the effectiveness of the proposed RVNN based ED for CR application. PMID- 27379319 TI - The Neuroepithelium Disruption Could Generate Autoantibodies against AQP4 and Cause Neuromyelitis Optica and Hydrocephalus. AB - Neuromyelitis optica is an inflammatory disease characterized by neuritis and myelitis of the optic nerve. Its physiopathology is connected with the aquaporin 4 water channel, since antibodies against aquaporin-4 have been found in the cerebrospinal fluid and blood of neuromyelitis optica patients. The seropositivity for aquaporin-4 antibodies is used for the diagnosis of neuromyelitis optica or neuromyelitis optica spectrum disease. On the other hand, aquaporin-4 is expressed in astrocyte feet in the brain-blood barrier and subventricular zones of the brain ventricles. Aquaporin-4 expression is high in cerebrospinal fluid in hydrocephalus. Furthermore, neuroepithelial denudation precedes noncommunicating hydrocephalus and this neuroepithelial disruption could allow aquaporin-4 to reach anomalous brain areas where it is unrecognized and induce the generation of aquaporin-4 antibodies which could cause the neuromyelitis optica and certain types of hydrocephalus. PMID- 27379320 TI - Improvements of Jensen-Type Inequalities for Diamond-alpha Integrals. AB - We give further improvements of the Jensen inequality and its converse on time scales, allowing also negative weights. These results generalize the Jensen inequality and its converse for both discrete and continuous cases. Further, we investigate the exponential and logarithmic convexity of the differences between the left-hand side and the right-hand side of these inequalities and present several families of functions for which these results can be applied. PMID- 27379321 TI - Evaluation of Root Canal Configuration of Mandibular First Molars in a Palestinian Population by Using Cone-Beam Computed Tomography: An Ex Vivo Study. AB - Aim. The purpose of this study was to investigate the number of canals and variations in root canal configuration in the mandibular permanent first molar teeth of a Palestinian population using cone-beam computed tomography (CBCT). Methods. A sample of 320 extracted double-rooted mandibular permanent first molars from Palestinian population was collected for this study and scanned with CBCT scanner. The following observations were made: number of root canals per root and canal configuration in each root based on Vertucci's classification. Results. Of the 320 mandibular first molars analyzed, 174 (54.4%) had three canals, 132 teeth (41.3%) had four canals, and only four teeth had two canals. The most common canal configuration in the mesial roots was Vertucci type IV (53.8%) followed by type II (38.8%). In the distal roots, the most prevalent canal configuration was Vertucci type I (57.5%) followed by type II ( 22.5%) and type III (10.6%). Conclusion. Our results showed that the number of canals and canal configuration in Palestinian population were consistent with previously reported data. The present study also indicates that CBCT is helpful as a diagnostic tool for the investigation of root canal morphology. PMID- 27379322 TI - Hypertrophic Scar Formation on Application of Terpenoid Fraction of Tuberous Root of Mirabilis jalapa L. on Excision Wound Model in Wistar Albino Rats. AB - The study was designed to evaluate the effects of hydromethanolic extract of tuberous root of M. jalapa and its terpenoid and flavonoid fractions on cutaneous wound healing in Wistar Albino rats. The hydromethanolic extract was subfractionated by sequential extraction in solvents (moderately nonpolar to polar). The extract and its (terpenoid and flavonoid) fractions were used for cutaneous wound healing studies by using excision wound model on rat. Their effects on wound contraction rate, biochemical and histological changes, and expression of growth factors such as collagen 3A, basic fibroblast growth factor, and vascular endothelial growth factor were investigated. The results indicated that flavonoid treated group showed significant decrease (P < 0.05) in antioxidant enzyme level as compared to control in wound healing process, whereas terpenoid fraction showed significant increase (P < 0.05) in expression of growth factor levels but regeneration and remodeling stages were delayed due to formation of thicker ulcus layer and also there were no hair follicle-like blood capillaries formation which ultimately may lead to formation of hypertrophic scar of wound. Therefore, from this study, it can be concluded that terpenoid fraction prolongs proliferation phase and hence may have tendency to convert the wound into hypertrophic wound. PMID- 27379323 TI - Functional Evaluation in High Energy (Schatzker Type V and Type VI) Tibial Plateau Fractures Treated by Open Reduction and Internal Fixation. AB - Objective. To review functional outcome in high energy tibial plateau fractures treated by plating. Design. Retrospective analysis. Material and Methods. Sixty five patients with Schatzker type V and type VI tibial plateau fractures treated with open reduction and internal fixation using plates were included in the study. The functional evaluation of the patients was carried out with Oxford knee scoring. Results. Fifty-four cases (83%) had Oxford knee score between 40 and 48. Seven (10.7%) had score between 30 and 39, three (4.6%) had score between 20 and 29, and one patient (1.5%) had a score of 18. Delayed union was seen in two cases and nonunion was seen in one case. The superficial wound infection was noticed in (9.2%) patients which was resolved with regular dressings and oral antibiotics. Three (4.6%) patients had developed deep wound infection and one among them had developed osteomyelitis. Conclusion. Open reduction and internal fixation in high energy tibial plateau fractures can provide good functional results in appropriately selected cases. PMID- 27379324 TI - Hand Hygiene Practices in Medical Students: A Follow-Up Study. AB - Objective. The study was conducted to study the impact of various measures instituted to improve hand hygiene practices of the medical students after having documented poor hand hygiene awareness and compliance in a study conducted in 2012. Methods. A self-designed questionnaire based on World Health Organization's concept of "Five Moments for Hand Hygiene" was used to evaluate the awareness of the indications of hand hygiene. Compliance was observed during Objective Structured Clinical Examination (OSCE) sessions. Fifty-one students participated voluntarily in the study. Results. The awareness and compliance of hand hygiene among the medical students in 2014 had shown statistically significant improvement (P < 0.005) as compared to figures of the study conducted in 2012. Conclusion. Dedicated multifaceted intervention can improve the hand hygiene practices in medical students. PMID- 27379325 TI - Primary Clear Cell Carcinoma of the Urinary Bladder. AB - Primary clear cell carcinoma of the urinary bladder (PCCUB) is rare. Literature review has revealed 47 cases of PCCUB which commonly affects women. The histogenesis of PCCUB is not certain and Mullerian origin and urotheilal origin have been postulated. The microscopic characteristics of PCCUB include cells with abundant clear cytoplasm, arranged in a solid, glandular, tubulocystic, or papillary pattern. The cells may be flat or cuboidal with abundant clear eosinophilic cytoplasm. Hobnailing may be evident. PCCUB, on immunohistochemistry, stain positively with pan-cytokeratin, cytokeratin 7, and CA 125. PCCUB may manifest with visible haematuria, lower urinary tract symptoms, and discharge. There is no consensus opinion regarding the best treatment option for PCCUBs and patient outcomes are not very clear. Surgery has been the adopted treatment of choice. Differential diagnoses of PCCUB include nephrogenic metaplasia, urothelial carcinoma with clear cell cytoplasm, diffuse large B-cell lymphoma, and metastatic clear cell carcinoma with the primary originating elsewhere. Conclusions. A thorough radiological imaging assessment is required in cases of PCCUB to exclude a primary tumour elsewhere. Urologists and oncologists should report cases of PCCUB they encounter and should enter them into a multicentric trial to ascertain the best management option. PMID- 27379327 TI - Fatigue Life Assessment of 65Si7 Leaf Springs: A Comparative Study. AB - The experimental fatigue life prediction of leaf springs is a time consuming process. The engineers working in the field of leaf springs always face a challenge to formulate alternate methods of fatigue life assessment. The work presented in this paper provides alternate methods for fatigue life assessment of leaf springs. A 65Si7 light commercial vehicle leaf spring is chosen for this study. The experimental fatigue life and load rate are determined on a full scale leaf spring testing machine. Four alternate methods of fatigue life assessment have been depicted. Firstly by SAE spring design manual approach the fatigue test stroke is established and by the intersection of maximum and initial stress the fatigue life is predicted. The second method constitutes a graphical method based on modified Goodman's criteria. In the third method codes are written in FORTRAN for fatigue life assessment based on analytical technique. The fourth method consists of computer aided engineering tools. The CAD model of the leaf spring has been prepared in solid works and analyzed using ANSYS. Using CAE tools, ideal type of contact and meshing elements have been proposed. The method which provides fatigue life closer to experimental value and consumes less time is suggested. PMID- 27379326 TI - Meteorological Variables Associated with Stroke. AB - To elucidate relationships between meteorological variables and incidence of stroke, we studied patients diagnosed with stroke after presenting to the emergency department (May 1, 2010-August 8, 2011). Patient demographics and medical data were reviewed retrospectively with regional meteorological data. Across 467 days, 134 stroke events were recorded on 114 days. On stroke days, maximum temperature (max T) and atmospheric pressure (AP) combined were a significant predictor of stroke (max T odds ratio (OR) = 1.014, 95% confidence interval (CI) = 1.003-1.026, and P = 0.04; AP: OR = 1.033, 95% CI = 0.997-1.071, and P = 0.02). When the patient could identify the hour of the stroke, average temperature (avg T) was significantly higher than nonstroke hours (18.2 degrees C versus 16.16 degrees C, P = 0.04). Daily fluctuations in AP and avg T also had significant effects on stroke incidence (AP: OR = 0.629, 95% CI = 0.512-0.773, and P = 0.0001; avg T OR = 1.1399, 95% CI = 1.218-606, and P = 0.0001). Patient age, stroke history, body mass index, ethnicity, and sex were further contributors to stroke risk. Temperature, atmospheric pressure, and certain physiological conditions likely play roles in weather-related stroke susceptibility. The mechanisms driving these associations are not fully understood. PMID- 27379328 TI - Use of Nonspecific, Glutamic Acid-Free, Media and High Glycerol or High Amylase as Inducing Parameters for Screening Bacillus Isolates Having High Yield of Polyglutamic Acid. AB - Out of fifty-five Bacillus isolates obtained from ten different regional locations and sources, seven showed the ability to consistently produce specific extracellular polymeric substance (EPS) on rich as well as synthetic but nonspecific media which did not contain glutamic acid. The isolates were identified as either Bacillus licheniformis or Bacillus subtilis. The EPS from all isolates was resistant to alpha protease, proteinase K, and was thus of high molecular weight. Further it was detected after SDS-PAGE by methylene blue but not by coomassie blue R staining as in case of proteins with high proportion of acidic amino acids. Cell-free EPS, after acid hydrolysis, showed absence of carbohydrates and presence of only glutamic acid. Thus the native the EPS from all seven isolates was confirmed to be gamma polyglutamic acid (PGA) and not exopolysaccharide. The Bacillus isolate T which produced maximum polymer on all media tested had higher amylase: protease activity as compared to other strains. If inoculum was developed in rich medium as compared to synthetic medium, the PGA produced increased by twofold in the subsequent synthetic production medium. Similarly, use of inoculum consisting of young and vegetative cells also increased the PGA production by twofold though amount of inoculum did not affect yield of PGA. Though PGA was produced in even in the absence of glutamic acid supplementation in the production medium by all isolates, the yield of PGA increased by fourfold in the presence glutamic acid and the maximum yield was 30 g/l for isolate K. The supplementation of glutamine instead of glutamic acid into the medium caused an increase in the viscosity of the non-Newtonian solution of PGA. PMID- 27379329 TI - The Effect of Light Exposure on Water Sorption and Solubility of Self-Adhesive Resin Cements. AB - Purpose. To investigate the effect of light activation on the water sorption (WS) and solubility (SL) of resin cements after 24 h and 7 days. Methods. Disk-shaped specimens were prepared using five dual-polymerized cements (four self-adhesive [RelyX Unicem, MaxCem, SeT and G-Cem] and one conventional [Panavia F 2.0]) and divided according to the curing mode (direct light exposure or self-cure) and water immersion period (24 h or 7 days). Specimens were dry-stored and weighed daily until a constant mass was recorded (M1). Then, specimens were stored in water for either 24 h or 7 days and immediately weighed (M2). After desiccation, specimens were weighed again until a constant mass was achieved (M3). WS and SL were calculated and statistically analyzed by Kruskal-Wallis, Dunn and Mann Whitney U tests (alpha = 0.05%). Results. There was a significant increase in WS for all products after one-week immersion in water. The highest water uptake was observed for autopolymerized groups. Extended water immersion significantly affected the SL for most of autopolymerized cements. Significant differences between products were observed in both tests. Conclusions. The curing mode and the water immersion period may affect the mechanical stability of the resin cements, and these differences appear to be product-dependent. PMID- 27379330 TI - Functional Performance Testing and Patient Reported Outcomes following ACL Reconstruction: A Systematic Scoping Review. AB - Objective. A systematic scoping review of the literature to identify functional performance tests and patient reported outcomes for patients who undergo anterior cruciate ligament (ACL) reconstruction and rehabilitation that are used in clinical practice and research during the last decade. Methods. A literature search was conducted. Electronic databases used included Medline, PubMed, Cochrane Library, EMBASE, CINAHL, SPORTDiscus, PEDro, and AMED. The inclusion criteria were English language, publication between April 2004 and April 2014, and primary ACL reconstruction with objective and/or subjective outcomes used. Two authors screened the selected papers for title, abstract, and full-text in accordance with predefined inclusion and exclusion criteria. The methodological quality of all papers was assessed by a checklist of the Critical Appraisal Skills Programme (CASP). Results. A total of 16 papers were included with full text. Different authors used different study designs for functional performance testing which led to different outcomes that could not be compared. All papers used a measurement for quantity of functional performance except one study which used both quantity and quality outcomes. Several functional performance tests and patient reported outcomes were identified in this review. Conclusion. No extensive research has been carried out over the past 10 years to measure the quality of functional performance testing and control stability of patients following ACL reconstruction. However this study found that the measurement of functional performance following ACL reconstruction consisting of a one-leg hop for a set distance or a combination of different hops using limb symmetry index (LSI) was a main outcome parameter of several studies. A more extensive series of tests is suggested to measure both the quantitative and qualitative aspects of functional performance after the ACL reconstruction. The KOOS and the IKDC questionnaires are both measures that are increasingly being used for ACL reconstruction throughout the last decade. PMID- 27379331 TI - Immunological Testing Reveals Exposure to Malaria in the Hypoendemic Region of Iran. AB - Background. South eastern parts of Iran remain endemic for malaria infection. There is some concern that malaria infection may spread into Bushehr, which is located in the south western part bordering the Persian Gulf and at the periphery of the declared endemic region Hormozgan province due to frequency of visitors from eastern endemic areas and from neighboring malaria endemic countries. We investigated malaria prevalence in Bushehr. Methods and Results. Attempts were made to identify malaria active infection in blood smears and malaria specific antibody and antigens in serum samples. Traditional blood smears prepared from 1955 blood specimens yielded no definitive malaria positive case by microscopic technique. A total of 270 (13.8%) serum samples were positive for malaria antibodies. Using specific ELISA kits, presence of histidine rich proteins and lactate dehydrogenase antigens were investigated in serum samples. No histidine rich proteins specific for P. falciparum were detected amongst 270 antibody positive samples. However, six samples representing 0.3% of total population, were found to be positive for plasmodium pan specific lactate dehydrogenase antigens. This suggested the possibility of low level exposure to malaria in Bushehr community. Conclusions. Out of a total of 1955 samples tested, 270 (13.8%) were positive for malaria antibodies and six (0.3%) of these were positive for plasmodium-specific lactate dehydrogenase antigen suggesting a low level exposure to malaria in a hypoendemic region based on immunological testing. Since none of the 270 antibody samples were positive for histidine rich protein antigens, there is scope for further testing of blood samples by molecular methods such as polymerase chain reactions to confirm the plasmodium species and provide information valuable for future investigations. Our testing strategy for hypoemdemic malaria can be used as a template for investing malaria in 32 eliminating countries for testing ongoing transmission. This approach may be useful as a method in epidemiological studies. PMID- 27379333 TI - The Interdependency of the Morphological Variations of the Planktonic Foraminiferal Species Globigerina bulloides in Surface Sediments on the Environmental Parameters of the Southwestern Indian Ocean. AB - 18 surface sediment samples collected from a north-south transect along the Indian Ocean have been analyzed for planktonic Foraminifera content. Among the other planktonic foraminiferal faunas, Globigerina bulloides was present substantially in all samples. Census data of G. bulloides were measured for different parameters (average size, mean proloculus size, coiling direction, and number of chambers) and a Q-mode cluster analysis was applied on these data. Samples were segregated into two homogeneous clusters, each reflecting particular environmental conditions. Two clusters are as follows: (1) Cluster A, comprised of 6 samples and characterized by the highest range of foraminiferal and ecological parameters, except sea surface temperature and salinity which shows the lowest range, and (2) Cluster B, comprised of 12 samples and characterized by the lowest range of foraminiferal parameters and ecological parameters, except sea surface temperature and salinity which shows the highest range. The study suggests that the ecological parameters are the governing factors for the morphological characteristics of planktonic foraminiferal species G. bulloides. PMID- 27379332 TI - Epidemiologic Behavior and Estimation of an Optimal Cut-Off Point for Homeostasis Model Assessment-2 Insulin Resistance: A Report from a Venezuelan Population. AB - Background. Mathematical models such as Homeostasis Model Assessment have gained popularity in the evaluation of insulin resistance (IR). The purpose of this study was to estimate the optimal cut-off point for Homeostasis Model Assessment 2 Insulin Resistance (HOMA2-IR) in an adult population of Maracaibo, Venezuela. Methods. Descriptive, cross-sectional study with randomized, multistaged sampling included 2,026 adult individuals. IR was evaluated through HOMA2-IR calculation in 602 metabolically healthy individuals. For cut-off point estimation, two approaches were applied: HOMA2-IR percentile distribution and construction of ROC curves using sensitivity and specificity for selection. Results. HOMA2-IR arithmetic mean for the general population was 2.21 +/- 1.42, with 2.18 +/- 1.37 for women and 2.23 +/- 1.47 for men (P = 0.466). When calculating HOMA2-IR for the healthy reference population, the resulting p75 was 2.00. Using ROC curves, the selected cut-off point was 1.95, with an area under the curve of 0.801, sensibility of 75.3%, and specificity of 72.8%. Conclusions. We propose an optimal cut-off point of 2.00 for HOMA2-IR, offering high sensitivity and specificity, sufficient for proper assessment of IR in the adult population of our city, Maracaibo. The determination of population-specific cut-off points is needed to evaluate risk for public health problems, such as obesity and metabolic syndrome. PMID- 27379334 TI - Sentinel Lymph Node Biopsy Should Be Included with the Initial Surgery for High Risk Ductal Carcinoma-In-Situ. AB - Background. A proportion of those diagnosed preoperatively with ductal carcinoma in-situ (DCIS) will be histologically upgraded to invasive carcinoma. Repeat surgery for sentinel lymph node (SLN) biopsy will be required if it had not been included with the initial surgery. We reviewed the outcome of SLN biopsy performed with the initial surgery based on a preoperative diagnosis of DCIS and aimed to identify patients at risk of histological upgrade. Methods. Retrospective review of 294 consecutive female patients diagnosed with DCIS was performed at our institute from January 1, 2001, to December 31, 2008. Results. Of the 294 patients, 132 (44.9%) underwent SLN biopsy together with the initial surgery. The SLN was positive for metastases in 5 patients, all of whom had tumours that were histologically upgraded. Histological upgrade also occurred in 43 of the 127 patients (33.9%) in whom the SLN was negative for metastases. On multivariate analysis, histological upgrade was more likely if a mass was detected on mammogram, if the preoperative diagnosis was obtained with core biopsy and if microinvasion was reported in the biopsy. Conclusion. Patients in whom a preoperative diagnosis of DCIS is likely to be upgraded to invasive carcinoma will benefit from SLN biopsy being performed with the initial surgery. PMID- 27379335 TI - Integrated Duo Wavelength VCSEL Using an Electrically Pumped GaInAs/AlGaAs 980 nm Cavity at the Bottom and an Optically Pumped GaInAs/AlGaInAs 1550 nm Cavity on the Top. AB - In this work, an integrated single chip dual cavity VCSEL has been designed which comprises an electrically pumped 980 nm bottom VCSEL section fabricated using GaInAs/AlGaAs MQW active region and a 1550 nm top VCSEL section constructed using GaInAs/AlGaInAs MQW active region but optically pumped using half of the produced 980 nm light entering into it from the electrically pumped bottom cavity. In this design, the active region of the intracavity structure 980 nm VCSEL consists of 3 quantum wells (QWs) using Ga0.847In0.153As, 2 barriers using Al0.03Ga0.97As, and 2 separate confinement heterostructures (SCH) using the same material as the barrier. The active region of the top emitting 1550 nm VCSEL consists of 3 QWs using Ga0.47In0.52As, 2 barriers using Al0.3Ga0.17In0.53As, and 2 SCHs using the same material as the barrier. The top DBR and the bottom DBR mirror systems of the 1550 nm VCSEL section plus the top and bottom DBR mirror systems of the 980 nm VCSEL section have been formed using GaAs/Al0.8Ga0.2As. Computations show that the VCSEL is capable of producing 8.5 mW of power at 980 nm from the bottom side and 2 mW of power at the 1550 nm from top side. PMID- 27379336 TI - Determination of Catechin and Epicatechin Content in Chocolates by High Performance Liquid Chromatography. AB - A simple and sensitive reversed phase high-performance liquid chromatographic (HPLC) method has been developed for the determination of catechin and epicatechin in cocoa powder and chocolates. The separation was achieved on a reversed phase C 18 column (TARGA) 5 MUm by gradient elution with a flow rate of 1.0 mL/minute with an operating temperature of 30 degrees C and detection with a UV-Visible detector was at 280 nm. The method was validated for linearity, precision, intra- and interday precision, and accuracy. The developed method is successfully applied for the determination of catechin and epicatechin content in chocolates. The Godiva brand chocolate contains high concentration of epicatechin. PMID- 27379337 TI - Study of the Effect of Dillenia indica Fruit Mucilage on the Properties of Metformin Hydrochloride Loaded Spray Dried Microspheres. AB - Natural materials are preferred over synthetic counterparts because of their biodegradable and biocompatible nature. The present work was proposed to utilize mucilage from natural source for the development of controlled release formulation of metformin hydrochloride. Natural mucilaginous substance extracted from Dillenia indica L. (DI) fruit was used in fabricating controlled release microspheres. The microspheres were prepared by spray drying method under different formulation parameters. The prepared microspheres were studied for particle size, drug excipient compatibility, particle shape and surface morphologies, drug entrapment efficiency, mucoadhesivity, and in vitro drug release properties. The prepared microspheres exhibited mucoadhesive properties and demonstrated controlled release of metformin hydrochloride. The study reveals that the natural materials can be used for formulation of controlled release microspheres and would provide ample opportunities for further study. PMID- 27379338 TI - The Association between Early Artificial Amniotomy and Chorioamnionitis in Nulliparous Induction of Labor. AB - Objectives. To investigate whether early artificial amniotomy (AROM) <4 cm in nulliparous women admitted for induction of labor was associated with an increased rate of chorioamnionitis and cesarean section or a decreased time to vaginal delivery. Study Design. A retrospective cohort study was performed on nulliparous women with a term, singleton gestation and intact membranes who presented for induction of labor (January 2008 to December 2011). Chorioamnionitis was defined using ICD9 codes. Results. 1,567 women were enrolled; 25.4% underwent early AROM. Overall, the prevalence of chorioamnionitis was 12.4%, the rate of cesarean section was 32.2%, and the time from 4 cm cervical dilation to vaginal delivery was 413 min. Compared to women without AROM < 4 cm, early AROM did not affect overall chorioamnionitis rates (10.2 versus 13.2%, P = 0.12) but was associated with an increased cesarean section rate (40.2 versus 29.5%, P < 0.001). However, among those who delivered vaginally, AROM < 4 cm decreased the rate of chorioamnionitis (8.4 versus 14.6%, P = 0.01), which persisted when controlling for potential confounders (OR 0.55, 95% CI 0.33-0.92), and decreased the time from 4 cm dilation to vaginal delivery (329 versus 472 min, P < 0.001). Conclusions. Our findings do not suggest that early AROM is associated with an increased rate of clinical chorioamnionitis. PMID- 27379339 TI - Efficacy of Levofloxacin Based Triple and High-Dose PPI-Amoxicillin Dual Eradication Therapy for Helicobacter pylori after Failures of First- and Second Line Therapies. AB - Objectives. The aim of this study was to investigate and compare the eradication rate of Helicobacter pylori as the third-line triple therapy with rabeprazole (RPZ) + amoxicillin (AMPC) + levofloxacin (LVFX) and high-dose RPZ + AMPC. Methods. 51 patients who failed Japanese first-line (proton pump inhibitor (PPI) + AMPC + clarithromycin) and second-line (PPI + AMPC + metronidazole) eradication therapy were randomly assigned at a 1 : 1 ratio to one of the following third line eradication groups: (1) RAL group: RPZ 10 mg (b.i.d.), AMPC 750 mg (b.i.d.), and LVFX 500 mg (o.d.) for 10 days; (2) RA group: RPZ 10 mg (q.i.d.) and AMPC 500 mg (q.i.d.) for 14 days. Patients who failed to respond to third-line eradication therapy received salvage therapy. Results. The rates of eradication success, based on intention to treat (ITT) analysis, were 45.8% in the RAL group and 40.7% in the RA group. The overall eradication rates were 73.9% in the RAL group and 64.0% in the RA group. There was no significant difference between the two groups. Conclusions. The third-line triple therapy with RPZ, AMPC, and LVFX was as effective as that with high-dose RPZ and AMPC. PMID- 27379340 TI - Quantitative Analysis of Resorcinol from Marketed Hair Tonic Using Liquid Chromatographic Technique. AB - Quantitative estimation of resorcinol from marketed pharmaceutical formulation has been reported in this study. Resorcinol as a pharmaceutical ingredient has a broad spectrum of application but its application is limited due to its toxic side effects. Method for the accurate estimation of resorcinol is therefore essential. In the current study we have developed a chromatographic technique for its estimation from a marketed hair tonic meant for the treatment of several dermatological diseases of the scalp. A stainless steel column 25 cm in length and 4 mm internal diameter packed with octadecylsilane (5 um) was used for this purpose. The mobile phase was a mixture of phosphate buffer of pH 2.8 and acetonitrile. The flow rate was 0.6 mL.min(-1) and the detection wavelength was 280 nm. The method was found to be linear between concentration range 10.28 ug.mL(-1) to 71.96 ug.mL(-1) with r (2) value 0.999. The accuracy of the method and the intraday and interday precession study presents the applicability of the method for the estimation of resorcinol from any pharmaceutical and cosmetic product containing resorcinol. PMID- 27379341 TI - Safety Evaluation of Zingiber cassumunar Roxb. Rhizome Extract: Acute and Chronic Toxicity Studies in Rats. AB - Zingiber cassumunar Roxb. has been used for traditional medicine, but few studies have described its potential toxicity. In this study, the acute and chronic oral toxicity of Z. cassumunar extract granules were evaluated in Sprague-Dawley rats. The extract at a single dose of 5000 mg/kg body weight did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14 day observation period. However, a decrease in body weights was observed in treated males (P < 0.05). The weights of lung and kidney of treated females were increased (P < 0.05). Treated males were increased in spleen and epididymis weights (P < 0.05). In repeated dose 270-day oral toxicity study, the administration of the extracts at concentrations of 0.3, 3, 30, 11.25, 112.5, and 1,125 mg/kg body weight/day revealed no-treatment toxicity. Although certain endpoints among those monitored (i.e., organ weight, hematological parameters, and clinical chemistry) exhibited statistically significant effects, none was adverse. Gross and histological observations revealed no toxicity. Our findings suggest that the Z. cassumunar extract granules are well tolerated for both single and chronic administration. The oral no-observed-adverse-effect level (NOAEL) for the extract was 1,125 mg/kg body weight/day for males and females. PMID- 27379342 TI - Protective Effects of Quercetin against Dimethoate-Induced Cytotoxicity and Genotoxicity in Allium sativum Test. AB - The present investigation was directed to study the possible protective activity of quercetin-a natural antioxidant against dimethoate-induced cyto- and genotoxicity in meristematic cells of Allium sativum. So far there is no report on the biological properties of quercetin in plant test systems. Chromosome breaks, multipolar anaphase, stick chromosome, and mitotic activity were undertaken in the current study as markers of cyto- and genotoxicity. Untreated control, quercetin controls (@ 5, 10 and 20 MUg/mL for 3 h), and dimethoate exposed groups (@ 100 and 200 MUg/mL for 3 h) were maintained. For protection against cytogenotoxicity, the root tip cells treated with dimethoate at 100 and 200 MUg/mL for 3 h and quercetin treatment at 5, 10, and 20 MUg/mL for 16 h, prior to dimethoate treatment, were undertaken. Quercetin was found to be neither cytotoxic nor genotoxic in Allium sativum control at these doses. A significant increase (P < 0.05) in chromosomal aberrations was noted in dimethoate treated Allium. Pretreatment of Allium sativum with quercetin significantly (P < 0.05) reduced dimethoate-induced genotoxicity and cytotoxicity in meristematic cells, and these effects were dose dependent. In conclusion, quercetin has a protective role in the abatement of dimethoate-induced cyto- and genotoxicity in the meristematic cells of Allium sativum that resides, at least in part, on its antioxidant effects. PMID- 27379343 TI - Identification of small molecule inhibitors that block the Toxoplasma gondii rhoptry kinase ROP18. AB - The protozoan parasite Toxoplasma gondii secretes a family of serine-threonine protein kinases into its host cell in order to disrupt signaling and alter immune responses. One prominent secretory effector is the rhoptry protein 18 (ROP18), a serine-threonine kinase that phosphorylates immunity related GTPases (IRGs) and hence blocks interferon gamma-mediated responses in rodent cells. Previous genetic studies show that ROP18 is a major virulence component of T. gondii strains from North and South America. Here, we implemented a high throughput screen to identify small molecule inhibitors of ROP18 in vitro and subsequently validated their specificity within infected cells. Although ROP18 was not susceptible to many kinase-directed inhibitors that affect mammalian kinases, the screen identified several sub micromolar inhibitors that belong to three chemical scaffolds: oxindoles, 6-azaquinazolines, and pyrazolopyridines. Treatment of interferon gamma-activated cells with one of these inhibitors enhanced immunity related GTPase recruitment to wild type parasites, recapitulating the defect of Deltarop18 mutant parasites, consistent with targeting ROP18 within infected cells. These compounds provide useful starting points for chemical biology experiments or as leads for therapeutic interventions designed to reduce parasite virulence. PMID- 27379345 TI - New Analytical Tools for Evaluating Dental Care Systems - Results for Germany and Selected Highly Developed Countries. AB - OBJECTIVE: To propose new analytical tools that facilitate the obtention of quantifiable results for evaluating different dental care systems. METHODS: The paper describes the construction of a composite indicator that measures dental health on a population basis in one overall indicator, the Dental Health Index (DHI). If the DHI is combined with a Dental Care Cost Index, an efficiency index (EI) can be created. RESULTS: The use of these new instruments for analysing different dental care systems reveals that the Swedish and Danish populations enjoy the best dental health status, followed by US, Japanese, Australian and Canadian citizens. Germany ranks in the middle, while the Dutch and Finnish populations enjoy a lesser degree of dental health. Advanced dental health can be achieved in any oral healthcare system, irrespective of the underlying cost sharing and funding structures. As a benchmark for industrialised countries, cost levels for dental care between 0.5% and 0.7% of GDP, seem to be the international norm. A population's dental status is determined by the degree to which preventive and tooth-preserving treatment approaches are practised, also amongst adults. CONCLUSION: The new instruments broaden the diagnostic possibilities for investigating different dental care systems. The greater the degree to which preventive and tooth-preserving treatment methods for the entire population are incorporated in daily clinical practice, the faster and better such systems progress and perform in terms of efficacy and efficiency. PMID- 27379344 TI - 15N Hyperpolarization of Imidazole-15N2 for Magnetic Resonance pH Sensing via SABRE-SHEATH. AB - 15N nuclear spins of imidazole-15N2 were hyperpolarized using NMR signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH). A 15N NMR signal enhancement of ~2000-fold at 9.4 T is reported using parahydrogen gas (~50% para-) and ~0.1 M imidazole-15N2 in methanol:aqueous buffer (~1:1). Proton binding to a 15N site of imidazole occurs at physiological pH (pKa ~ 7.0), and the binding event changes the 15N isotropic chemical shift by ~30 ppm. These properties are ideal for in vivo pH sensing. Additionally, imidazoles have low toxicity and are readily incorporated into a wide range of biomolecules. 15N-Imidazole SABRE-SHEATH hyperpolarization potentially enables pH sensing on scales ranging from peptide and protein molecules to living organisms. PMID- 27379346 TI - Effect of Capsaicin Cream on the Secretion of the Submandibular and Parotid Gland in the General Population with Different Chilli-eating Habits. AB - OBJECTIVE: To investigate the effect of capsaicin cream on the secretion of the submandibular gland (SMG) and the parotid gland (PG) in the general population, with different chilli-eating habits. METHODS: In two groups with different chilli eating habits, the salivary flow rate of the SMG and the PG was detected at statics and different times, after application of capsaicin cream. RESULTS: In both groups, the topical application of capsaicin cream could significantly increase the salivary secretion of SMG (P < 0.05), but the increase in the salivary flow rate of the SMG between the two groups had no significant difference (P > 0.05). On the other hand, although the salivary flow rate of PG also increased after stimulation, the increase had no statistical difference (P > 0.05). CONCLUSION: The application of capsaicin cream can effectively promote the secretion of the SMG and the PG, and its effect is independent of chilli-eating habits, which indicates that topical application of capsaicin cream can be considered as a potential treatment for the hypofunction of the salivary gland. PMID- 27379347 TI - Asymmetric Head Gear: A Comparison between Unilateral Outer Bow Expansion and Unilateral Outer Bow Shortening - an Energy Approach using the Finite Element Method. AB - OBJECTIVE: To compare the influence of outer bow length difference and unilateral outer bow expansion on the 'asymmetric effect' of the headgear. METHODS: Twelve 3D finite element models of a headgear with two tubes were designed, which were similar except for the outer bow length or the degree of unilateral expansion in Solid-Works 2011. A 3N force was applied to the outer bow ends in ANSYS Workbench 12.1 and the distalising, lateral forces to molars, moments and the energy of the system were evaluated. RESULTS: As the degree of unilateral expansion increased, the net differences in all findings were increased up to a point, and then changed. There was an increasing pattern in the length difference group. Buccal movement was observed in the intact/shorter side molar. CONCLUSION: Unilateral shortened outer bow asymmetric headgears are more efficient and more predictable in clinical application than the unilateral outer bow expansion. PMID- 27379348 TI - Osteoprotegerin Promotes Cementoblastic Activity of Murine Cementoblast Cell Line in vitro. AB - OBJECTIVE: To investigate the effect of osteoprotegerin (OPG) on the cementoblastic activity of a clonal population of immortalised murine cementoblasts (OCCM-30) in vitro. METHODS: OCCM-30 cells were transiently transfected with the mouse OPG using the Avalanche transfection reagent. The ectopic expression of OPG was confirmed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. The cell counting Kit-8 assay was used to investigate the effect of OPG on cell proliferation. The expression levels of cementoblastic-related mRNA and protein in the transfected OCCM-30 cells were detected using real-time PCR, Western blotting and immunohistochemical staining. RESULTS: Satisfactory transfection efficiency was observed 48 h after transfection. The results of the cell proliferation assay indicated that the expansion rate of the OPG transfection group was greater than that of the control group at both 72 h and 96 h. The mRNA levels of osterix (Osx), protein kinase B (Akt1), cementum attachment protein (CAP) and osteopontin (Opn) were significantly upregulated (P < 0.05) in the OPG group. Protein levels of OPN, bone sialoprotein II (BSP II), osteocalcin (OC) and CAP, which are responsible for osteogenetic and cementoblastic activity, were significantly increased in the OPG-overexpressing group. CONCLUSION: Overexpression of OPG in OCCM-30 cells promotes cementoblastic activity. PMID- 27379349 TI - Inhibition of Enterococcus faecalis by Calcium Peroxide. AB - OBJECTIVE: To investigate the inhibition of Enterococcus faecalis by calcium peroxide (CaO2). METHODS: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Enterococcus faecalis by CaO2 and calcium hydroxide (Ca(OH)2) were determined by direct exposure tests (n = 10). The inhibition zone of E. faecalis mycoderm treated with CaO2 and Ca(OH)2 paste (53% w/w) was observed using agar diffusion tests (n = 20). The inhibition of E. faecalis biofilms by CaO2/phosphate-buffered saline (PBS) and Ca(OH)2/PBS suspensions were observed using confocal laser scanning microscopy and the percentages of live bacteria in the biofilms calculated. RESULTS: The MIC of Ca(OH)2 (4.5 to 5.5 mg/ml) was higher than the MIC of CaO2 (2.0 to 2.5 mg/ml) (P < 0.05), and the MBC of Ca(OH)2 (14.5 to 15.5 mg/ml) was higher than that of CaO2 (3.0 to 3.5 mg/ml) (P < 0.05). No inhibition zone was observed for Ca(OH)2 in agar diffusion tests, while the diameter of the inhibition zone around CaO2 was 8.6 +/- 0.4 mm. There were significant differences between groups in the percentages of surviving bacteria in E. faecalis biofilms after treatment (P < 0.05): group CaO2 < group Ca(OH)2 < group PBS < group BHI. CONCLUSION: The inhibition of E. faecalis by CaO2 was greater than that by Ca(OH)2. PMID- 27379350 TI - Partial Pulpotomy of Immature Teeth with Apical Periodontitis using Bioceramics and Mineral Trioxide Aggregate: A Report of Three Cases. AB - Pulpal necrosis of an immature permanent tooth with an open apex poses a challenge for the clinician. The conventional apexification technique using calcium hydroxide has yielded short-term success, but this technique has inevitable shortcomings. Hence, this case series aimed to evaluate the effectiveness of using bioceramics (iRoot BP) or mineral trioxide aggregate (MTA) for partial pulpotomies. Three boys aged 9 to 11 years old presented with partial pulp necrosis and symptomatic apical periodontitis of the mandibular right and left second premolar. The involved teeth were treated with a partial pulpotomy using either iRoot BP (case 1 and 2) or MTA (case 3). At the 8-month follow-up, no abnormal clinical signs or symptoms were observed. Periapical radiographs revealed a significant reduction in periapical radiolucency, a marked increase in the root canal wall thickness and ongoing closure of the apical opening. The bioceramic material (iRoot BP) and MTA both produced successful outcomes in the partial pulpotomy of immature teeth with partial pulp necrosis and apical periodontitis. However, iRoot BP was superior in terms of ease of clinical application, and would therefore be a better treatment alternative than MTA. PMID- 27379351 TI - Willingness of Rhode Island Dentists to Provide Limited Preventive Primary Care. AB - In response to the shortage of primary care physicians and the need for greater intercollaboration among health professionals, dentists with sufficient medical and surgical training are an untapped resource to provide limited preventive primary care (LPPC), such as chairside screening for chronic diseases. The objective of this study was to determine attitudes of Rhode Island dentists toward becoming more involved in the overall health of their patients. Using a 5 point scale (1 being highest), a pretested survey was administered to 92 respondent RI dentists who were asked to indicate their willingness to become more involved in patients' overall health, and undergo additional training to provide LPPC. Their moderate level of willingness was offset by great concern for liability, with older dentists being significantly more willing to assume these additional responsibilities than younger dentists (p< .05). Rank order of designation of oral health providers among dentist, dental physician, oral physician, odontologist, stomatologist, and stomiatrist was still dentist first, but with no significant difference between the mean ranks of dentist and oral physician.[Full article available at http://rimed.org/rimedicaljournal-2016 07.asp, free with no login]. PMID- 27379352 TI - Geriatric Issues in Older Dialysis Patients. AB - Geriatric syndrome is common among older patients on dialysis. Basic knowledge about its prevalence and management is crucial for nephrologists to provide standard patient care. In busy clinical settings, up-to-date and holistic medical care can be delivered to elderly dialysis patients by collaboration of nephrology and geriatrics teams, or in part by training nephrology fellows the basics of geriatrics. [Full article available at http://rimed.org/rimedicaljournal-2016 07.asp, free with no login]. PMID- 27379353 TI - Influence of Medical Student Debt on the Decision to Pursue Careers in Primary Care. AB - PURPOSE: To determine if medical student debt has an effect on medical student specialty choice. METHODS: A cross-sectional survey was distributed to students at 12 medical schools across the United States to assess the effect of debt on specialty choice. RESULTS: In total, 415 students responded to the survey; 98 medical students reported that they were pursuing a primary care residency (PCR) and 250 reported that they were pursing a non-primary care residency (NPCR). There was no significant difference in average student loan debt anticipated by medical students pursing PCR and NPCR ($142,217 vs $150,784; P>0.46). Medical students pursuing a PCR reported lower estimated salaries on average than medical students pursuing NPCR ($137,711 vs $241,804; p<0.01). Of the surveyed students, 62% of students who are pursuing PCR and 77% of the students who are pursuing a NPCR would not have pursued medicine as a career if residents were responsible for paying tuition. CONCLUSION: This study revealed no significant difference between the student debt of medical students pursuing PCR compared to those who are pursuing a NPCR. However, a large majority of medical students would not pursue a career in medicine if faced with the responsibility of paying tuition for residency. [Full article available at http://rimed.org/rimedicaljournal-2016 07.asp, free with no login]. PMID- 27379354 TI - Surveillance of Travel-Related Mosquito-borne Illness in Rhode Island. AB - Malaria and Dengue are some of the common infections occurring in persons traveling to countries endemic for these infections. Chinkungunya virus infection is another illness that can occur in people who have travelled to areas endemic for chikungunya virus infection. Herein we report cases of malaria, dengue, and chikungunya in Newport Hospital, The Miriam Hospital and Rhode Island Hospital between January 1, 2010 and December 31, 2014. [Full article available at http://rimed.org/rimedicaljournal-2016-07.asp, free with no login]. PMID- 27379355 TI - Atypical presentation of infective endocarditis. AB - The HACEK group of organisms are one of the infrequent causes of infective endocarditis. Infective endocarditis should be recognized and treated promptly to prevent excessive morbidity and mortality associated with the disease. Sometimes the diagnosis is delayed due to vague and subtle presentation. Through this case report, risk factors of Cardiobacterium hominis endocarditis and its atypical presentation is illustrated to increase the recognition of infective endocarditis as one of the differential diagnosis. [Full article available at http://rimed.org/rimedicaljournal-2016-07.asp, free with no login]. PMID- 27379356 TI - A case of Ochrobactrum anthropi-induced septic shock and infective endocarditis. AB - Ochrobactrum anthropi is a gram-negative rod of low virulence. Infections due to this organism are uncommon; however in immunocompromised hosts it can cause severe infections. Among the many infections it can cause, infective endocarditis is very rare. Even rarer is infective endocarditis of the native valves, as Ochrobactrum antropi affects damaged or prosthetic valves almost exclusively. This case describes native valve endocarditis due to Ochrobactrum anthropi. [Full article available at http://rimed.org/rimedicaljournal-2016-07.asp, free with no login]. PMID- 27379358 TI - The Misperceived Curmudgeon. PMID- 27379357 TI - The pharma-fever that almost got away. PMID- 27379359 TI - An aerodynamic assisted miniature mass spectrometer for enhanced volatile sample analysis. AB - Previously, we have reported the development of a miniature mass spectrometer with a continuous atmospheric pressure interface (CAPI), and the use of it for non-volatile sample analysis, such as drugs, peptides and proteins. However due to the diffusion effects in the CAPI, especially stronger for light ions, the instrument shows low detection sensitivities for volatile samples when coupling with an atmosphere pressure chemical ionization (APCI) source (>ppmv). In this study, an in-vacuum plasma ionization source was designed and integrated into the system. By performing ionization in the first vacuum stage, ion transfer loss through the CAPI was minimized and tens of ppbv level detection sensitivities were achieved for volatile samples. Due to its improved sensitivity, chemical source tracing was demonstrated in an indoor environment as a simple proof-of concept example. Furthermore, an aerodynamic sampling method was developed to facilitate directional sample transfer towards the miniature mass spectrometer in an open environment. By coupling this aerodynamic method with the miniature mass spectrometer, remote chemical source sensing could be achieved at a distance of more than two meters. This aerodynamic sampling method could also be applied to other mass spectrometry instruments for enhanced sample sampling in open environments. PMID- 27379360 TI - Structures and magnetism of mono-palladium and mono-platinum doped Au25(PET)18 nanoclusters. AB - Herein we report three important results of widespread interest, which are (1) the crystal structure of [Au24Pt(PET)18](0), (2) the crystal structure of [Au24Pd(PET)18](0) and (3) the main source of magnetism in [Au25(PET)18](0). PMID- 27379362 TI - In Response. PMID- 27379363 TI - The author responds. PMID- 27379361 TI - A novel anticancer theranostic pro-prodrug based on hypoxia and photo sequential control. AB - A novel anticancer pro-prodrug (GMC-CAE-NO2) with diagnosis and therapy functions based on hypoxia and photo sequential control was designed. It provides a platform for constructing theranostic pro-prodrugs to release active drugs controlled by hypoxic status and UV illumination. PMID- 27379365 TI - New survey reveals the value of being a Cat Friendly Practice. PMID- 27379364 TI - Two of the roundtable participants respond. PMID- 27379366 TI - Winn Feline Foundation--fostering improvements in feline health. PMID- 27379367 TI - NICE menopause guidelines: A war of words and a war of numbers. PMID- 27379369 TI - Retraction notice to '1alpha,25(OH)2D3-induced DNA methylation suppresses the human CYP27B1 gene'. PMID- 27379368 TI - Guidelines reaffirm diagnosis of premature ovarian insufficiency. PMID- 27379370 TI - Autocrine Positive Feedback Regulation of Prolactin Release From Tilapia Prolactin Cells and Its Modulation by Extracellular Osmolality. AB - Prolactin (PRL) is a vertebrate hormone with diverse actions in osmoregulation, metabolism, reproduction, and in growth and development. Osmoregulation is fundamental to maintaining the functional structure of the macromolecules that conduct the business of life. In teleost fish, PRL plays a critical role in osmoregulation in fresh water. Appropriately, PRL cells of the tilapia are directly osmosensitive, with PRL secretion increasing as extracellular osmolality falls. Using a model system that employs dispersed PRL cells from the euryhaline teleost fish, Oreochromis mossambicus, we investigated the autocrine regulation of PRL cell function. Unknown was whether these PRL cells might also be sensitive to autocrine feedback and whether possible autocrine regulation might interact with the well-established regulation by physiologically relevant changes in extracellular osmolality. In the cell-perfusion system, ovine PRL and two isoforms of tilapia PRL (tPRL), tPRL177 and tPRL188, stimulated the release of tPRLs from the dispersed PRL cells. These effects were significant within 5-10 minutes and lasted the entire course of exposure, ceasing within 5-10 minutes of removal of tested PRLs from the perifusion medium. The magnitude of response varied between tPRL177 and tPRL188 and was modulated by extracellular osmolality. On the other hand, the gene expression of tPRLs was mainly unchanged or suppressed by static incubations of PRL cells with added PRLs. By demonstrating the regulatory complexity driven by positive autocrine feedback and its interaction with osmotic stimuli, these findings expand upon the knowledge that pituitary PRL cells are regulated complexly through multiple factors and interactions. PMID- 27379371 TI - Up-regulation of 11beta-Hydroxysteroid Dehydrogenase Type 2 Expression by Hedgehog Ligand Contributes to the Conversion of Cortisol Into Cortisone. AB - The cortisol-inactivating enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) that catalyzes the intracellular inactivation of glucocorticoids plays a pivotal role in human pregnant maintenance and normal fetal development. Given the fact that the main components of Hedgehog (HH) signaling pathway are predominantly expressed in syncytial layer of human placental villi where 11beta HSD2 is robustly expressed, in the present study, we have investigated the potential roles and underlying mechanisms of HH signaling in 11beta-HSD2 expression. Activation of HH signaling by a variety of approaches robustly induced 11beta-HSD2 expression as well as the 11beta-HSD2 activity, whereas suppression of HH signaling significantly attenuated 11beta-HSD2 expression as well as the 11beta-HSD2 activity in both human primary cytotrophoblasts and trophoblast-like BeWo cells. Moreover, among glioma-associated oncogene (GLI) family transcriptional factors in HH signaling, knockdown of GLI2 but not GLI1 and GLI3 significantly attenuated HH-induced 11beta-HSD2 expression and activity, and overexpression of GLI2 activator alone was sufficient to induce 11beta-HSD2 expression and activity. Finally, GLI2 not only directly bound to the promoter region of gene hsd11b2 to transactivate hsd11b2 but also formed a heterodimer with RNA polymerase II, an enzyme that catalyzes the transcription of DNA to synthesize mRNAs, resulting in up-regulation of hsd11b2 gene transcription. Taken together, the present study has uncovered a hitherto uncharacterized role of HH/GLI2 signaling in 11beta-HSD2 regulation, implicating that HH signaling through GLI2 could be required for the human pregnant maintenance and fetal development. PMID- 27379373 TI - Marcus Bell-Shaped Electron Transfer Kinetics Observed in an Arrhenius Plot. AB - The Marcus theory of electron transfer predicts a bell-shaped dependence of the reaction rate on the reaction free energy. The top of the "inverted parabola" corresponds to zero activation barrier when the electron-transfer reorganization energy and the reaction free energy add up to zero. Although this point has traditionally been reached by altering the chemical structures of donors and acceptors, the theory suggests that it can also be reached by varying other parameters of the system including temperature. We find here dramatic evidence of this phenomenon from experiments on a fullerene-porphyrin dyad. Following photoinduced electron transfer, the rate of charge recombination shows a bell shaped dependence on the inverse temperature, first increasing with cooling and then decreasing at still lower temperatures. This non-Arrhenius rate law is a result of a strong, approximately hyperbolic temperature variation of the reorganization energy and the reaction free energy. Our results provide potentially the cleanest confirmation of the Marcus energy gap law so far since no modification of the chemical structure is involved. PMID- 27379372 TI - Differences in Attributions for Public and Private Face-to-face and Cyber Victimization Among Adolescents in China, Cyprus, the Czech Republic, India, Japan, and the United States. AB - The authors' aim was to investigate gender and cultural differences in the attributions used to determine causality for hypothetical public and private face to-face and cyber victimization scenarios among 3,432 adolescents (age range = 11 15 years; 49% girls) from China, Cyprus, the Czech Republic, India, Japan, and the United States, while accounting for their individualism and collectivism. Adolescents completed a questionnaire on cultural values and read four hypothetical victimization scenarios, including public face-to-face victimization, public cyber victimization, private face-to-face victimization, and private cyber victimization. After reading the scenarios, they rated different attributions (i.e., self-blame, aggressor-blame, joking, normative, conflict) according to how strongly they believed the attributions explained why victimization occurred. Overall, adolescents reported that they would utilize the attributions of self-blame, aggressor-blame, and normative more for public forms of victimization and face-to-face victimization than for private forms of victimization and cyber victimization. Differences were found according to gender and country of origin as well. Such findings underscore the importance of delineating between different forms of victimization when examining adolescents' attributions. PMID- 27379374 TI - The effects of item material on encoding strategies: Survival processing compared to the method of loci. AB - When imagining being stranded in the grasslands of a foreign land without any basic survival material, participants have a magnificent memory for words rated according to their usefulness in this particular situation. Numerous studies could demonstrate that survival processing boosts memory performance more than other memory enhancing techniques. The method of loci is an old mnemonic strategy used to enhance serial recall. This method encompasses navigating mentally through a familiar environment and placing the to-be-remembered items in specific locations. In the later recall phase, the participant re-imagines walking through the environment, "looking" for the to-be-remembered items. In two studies, we compared the survival scenario with the method of loci and two different control conditions. In addition, we manipulated the used word-material on two different dimensions (imageability and relevance) to analyse its influences on the two methods. For words high in imageability, we found that memory performance in the survival condition is comparable to the method of loci. However, for words low in imageability the method of loci proved to be more effective than survival processing. Furthermore, we found that survival relevance has a high impact on the amount of the survival processing effect, even when imageability is low. PMID- 27379375 TI - Microcavity-Integrated Carbon Nanotube Photodetectors. AB - Carbon nanotubes (CNTs) are considered to be highly promising nanomaterials for multiwavelength, room-temperature infrared detection applications. Here, we demonstrate a single-tube diode photodetector monolithically integrated with a Fabry-Perot microcavity. A ~6-fold enhanced optical absorption can be achieved, because of the confined effect of the designed optical mode. Furthermore, taking advantage of Van-Hove-singularity band structures in CNTs, we open the possibility of developing chirality-specific (n,m) CNT-film-based signal detectors. Utilizing a concept of the "resonance and off-resonance" cavity, we achieved cavity-integrated chirality-sorted CNT-film detectors working at zero bias and resonance-allowed mode, for specific target signal detection. The detectors exhibited a higher suppression ratio until a power density of 0.07 W cm(-2) and photocurrent of 5 pA, and the spectral full width at half-maximum is ~33 nm at a signal wavelength of 1200 nm. Further, with multiple array detectors aiming at different target signals integrated on a chip, a multiwavelength signal detector system can be expected to have applications in the fields of monitoring, biosensing, color imaging, signal capture, and on-chip or space information transfers. The approach can also bring other nanomaterials into on-chip or information optoelectronics, regardless of the available doping polarity. PMID- 27379376 TI - Speech perception in medico-legal assessment of hearing disabilities. AB - OBJECTIVE: Examination of Danish data for medico-legal compensations regarding hearing disabilities. The study purposes are: (1) to investigate whether discrimination scores (DSs) relate to patients' subjective experience of their hearing and communication ability (the latter referring to audio-visual perception), (2) to compare DSs from different discrimination tests (auditory/audio-visual perception and without/with noise), and (3) to relate different handicap measures in the scaling used for compensation purposes in Denmark. DESIGN: Data from a 15 year period (1999-2014) were collected and analysed. STUDY SAMPLE: The data set includes 466 patients, from which 50 were omitted due to suspicion of having exaggerated their hearing disabilities. RESULTS: The DSs relate well to the patients' subjective experience of their speech perception ability. By comparing DSs for different test setups it was found that adding noise entails a relatively more difficult listening condition than removing visual cues. The hearing and communication handicap degrees were found to agree, whereas the measured handicap degrees tended to be higher than the self-assessed handicap degrees. CONCLUSIONS: The DSs can be used to assess patients' hearing and communication abilities. The difference in the obtained handicap degrees emphasizes the importance of collecting self-assessed as well as measured handicap degrees. PMID- 27379377 TI - Interrupted Time Series Analysis of the Effect of Rescheduling Alprazolam in Australia: Taking Control of Prescription Drug Use. PMID- 27379378 TI - Reducing the Harmful Effects of Infrared Radiation on the Skin Using Bicosomes Incorporating beta-Carotene. AB - AIM: In this work the effect of infrared (IR) radiation, at temperatures between 25 and 30 degrees C, on the formation of free radicals (FRs) in the skin is studied. Additionally, the influence of IR radiation at high temperatures in the degradation of skin collagen is evaluated. In both experiments the protective effect against IR radiation of phospholipid nanostructures (bicosomes) incorporating beta-carotene (Bcb) is also evaluated. METHODS: The formation of FRs in skin under IR exposure was measured near physiological temperatures (25-30 degrees C) using 5,5-dimethyl-1-pyrroline-N-oxide spin trap and electron paramagnetic resonance (EPR) spectroscopy. The study of the collagen structure was performed by small-angle X-ray scattering using synchrotron radiation. RESULTS: EPR results showed an increase in the hydroxyl radical in the irradiated skin compared to the native skin. The skin collagen was degraded by IR exposure at high temperatures of approximately 65 degrees C. The treatment with Bcb reduced the formation of FRs and kept the structure of collagen. CONCLUSIONS: The formation of FRs by IR radiation does not depend on the increase of skin temperature. The decrease of FRs and the preservation of collagen fibers in the skin treated with Bcb indicate the potential of this lipid system to protect skin under IR exposure. PMID- 27379380 TI - Hypervalent Iodine(III) Mediated Synthesis of 3-Substituted 5-Amino-1,2,4 thiadiazoles through Intramolecular Oxidative S-N Bond Formation. AB - An efficient synthesis of 3-substituted-5-arylamino-1,2,4-thiadiazoles through intramolecular oxidative S-N bond formation of imidoyl thioureas by phenyliodine(III) bis(trifluoroacetate) is reported. The protocol features a metal-free approach, broad substrate scope, very short reaction times, good to excellent yields, and simple starting materials. PMID- 27379379 TI - Choline Ameliorates Disease Phenotypes in Human iPSC Models of Rett Syndrome. AB - Rett syndrome (RTT) is a postnatal neurodevelopmental disorder that primarily affects girls. Mutations in the methyl-CpG-binding protein 2 (MECP2) gene account for approximately 95 % of all RTT cases. To model RTT in vitro, we generated induced pluripotent stem cells (iPSCs) from fibroblasts of two RTT patients with different mutations (MECP2 (R306C) and MECP2 (1155Delta32)) in their MECP2 gene. We found that these iPSCs were capable of differentiating into functional neurons. Compared to control neurons, the RTT iPSC-derived cells had reduced soma size and a decreased amount of synaptic input, evident both as fewer Synapsin 1 positive puncta and a lower frequency of spontaneous excitatory postsynaptic currents. Supplementation of the culture media with choline rescued all of these defects. Choline supplementation may act through changes in the expression of choline acetyltransferase, an important enzyme in cholinergic signaling, and also through alterations in the lipid metabolite profiles of the RTT neurons. Our study elucidates the possible mechanistic pathways for the effect of choline on human RTT cell models, thereby illustrating the potential for using choline as a nutraceutical to treat RTT. PMID- 27379381 TI - Birthing postures and birth canal lacerations. AB - OBJECTIVE: This study was performed to assess the differences in the birth canal lacerations following the lateral and fours posture deliveries compared with those following the supine posture deliveries. METHODS: We examined the birth canal lacerations of our "low risk" pregnant women under the midwife-led delivery care at Japanese Red Cross Katsushika Maternity Hospital between April 2006 and March 2015. RESULTS: There were 3826, 1754 and 719 women who delivered with supine, lateral and fours postures. The rate of no laceration in the women who delivered with lateral posture was significant lower than that in the women who delivered with supine posture (OR 0.630, 95% CI 0.56-0.71, p < 0.01); however, the incidence of perineal laceration in the women who delivered with lateral posture was significant lower than that in the women who delivered with supine posture (OR 0.856, 95% CI 0.76-0.90, p < 0.01). The incidence of perineal laceration of third- or fourth-degree in the women who delivered with fours posture was significant higher than that in the women who delivered with supine posture (OR 2.28, 95% CI 1.2-4.2, p < 0.01). CONCLUSION: The current results may be to help for self-determination of birthing postures in prenatal women. PMID- 27379383 TI - Uranium Reduction by Fe(II) in the Presence of Montmorillonite and Nontronite. AB - Uranium(VI) interactions with three smectites (one montmorillonite and two nontronites - NAu1 and NAu2) were examined with 0, 1, and 2 mM aqueous concentrations of Fe(II) over the pH range of 3-9.5 in a background electrolyte of 100 mM NaCl and 1 mM CaCl2 in equilibration with 400 ppmv CO2(g) ([U(VI)] = 4 MUM and 0.5 g smectite/L). In the absence of Fe(II), no differences were observed in the U(VI) sorption curves for the three clay minerals. In the presence of 1 or 2 mM Fe(II), under anoxic conditions, U(VI) uptake by the smectites changed slightly between ~pH 3 and 6; however, uranium uptake increased significantly above ~pH 6 and was proportional to the concentration of Fe(II) added to the system, particularly at pH values >8. The uptake of Fe(II) showed a sharp edge starting from ~pH 6.5 with 95%-100% uptake occurring at pH values >7.5, with no difference observed between the iron-rich nontronites and montmorillonite. After 3 days of reaction at pH 7.6 (i.e., above the Fe(II) "sorption" edge), U(VI) was transformed to a mixture of U(IV) and U(VI) sorption complexes, and after 14 days of reaction, 100% of the U was found to be reduced to U(IV) in the form of nanocrystalline uraninite. In contrast, U remained as sorbed species until 14 days of reaction at pH 6.5. Ferrihydrite (NAu1), lepidocrocite, and magnetite (NAu2) were detected as secondary mineralization products upon reaction of the nontronites with Fe(II) but appeared to have no effect on the partitioning or speciation of uranium. PMID- 27379382 TI - Blocking TGF-beta Signaling Pathway Preserves Mitochondrial Proteostasis and Reduces Early Activation of PDGFRbeta+ Pericytes in Aristolochic Acid Induced Acute Kidney Injury in Wistar Male Rats. AB - BACKGROUND: The platelet-derived growth factor receptor beta (PDGFRbeta)+ perivascular cell activation becomes increasingly recognized as a main source of scar-associated kidney myofibroblasts and recently emerged as a new cellular therapeutic target. AIMS: In this regard, we first confirmed the presence of PDGFRbeta+ perivascular cells in a human case of end-stage aristolochic acid nephropathy (AAN) and thereafter we focused on the early fibrosis events of transforming growth factor beta (TGFbeta) inhibition in a rat model of AAN. MATERIALS AND METHODS: Neutralizing anti-TGFbeta antibody (1D11) and its control isotype (13C4) were administered (5 mg/kg, i.p.) at Days -1, 0, 2 and 4; AA (15 mg/kg, sc) was injected daily. RESULTS: At Day 5, 1D11 significantly suppressed p Smad2/3 signaling pathway improving renal function impairment, reduced the score of acute tubular necrosis, peritubular capillaritis, interstitial inflammation and neoangiogenesis. 1D11 markedly decreased interstitial edema, disruption of tubular basement membrane loss of brush border, cytoplasmic edema and organelle ultrastructure alterations (mitochondrial disruption and endoplasmic reticulum edema) in proximal tubular epithelial cells. Moreover, 1D11 significantly inhibited p-PERK activation and attenuated dysregulation of unfolded protein response (UPR) pathways, endoplasmic reticulum and mitochondrial proteostasis in vivo and in vitro. CONCLUSIONS: The early inhibition of p-Smad2/3 signaling pathway improved acute renal function impairment, partially prevented epithelial endothelial axis activation by maintaining PTEC proteostasis and reduced early PDGFRbeta+ pericytes-derived myofibroblasts accumulation. PMID- 27379384 TI - Diagnosis of Ocular Tuberculosis. AB - Ocular tuberculosis remains a presumptive clinical diagnosis, as the gold standard tests for diagnosing ocular tuberculosis are often not useful: Mycobacterium tuberculosis cultures require weeks to process on Lowenstein-Jenson media and have low yield from ocular samples; while acid-fast bacilli smears or polymerase chain reaction detection of M. tuberculosis DNA have low sensitivities. Thus, diagnosis is often based on suggestive clinical signs, which are supported by positive investigations: tuberculin skin test or interferon gamma release assays; chest X-ray findings suggestive of pulmonary tuberculosis, and/or evidence of associated systemic tuberculosis infections in the absence of other underlying disease. The aim of this review is to provide an update on the methods of diagnosing ocular tuberculosis, and discuss the challenges of its diagnosis. We also suggest a step-ladder approach to a more accurate diagnosis of ocular tuberculosis by combining the available diagnostic tests. PMID- 27379385 TI - Control of the Crystalline Morphology of Poly(l-lactide) by Addition of High Melting-Point Poly(l-lactide) and Its Effect on the Distribution of Multiwalled Carbon Nanotubes. AB - The key to fabricating conductive polymer/carbon nanotube (CNT) nanocomposites is controlling the distribution of CNTs in the polymer matrix. Here, an effective and simple approach for controlling the distribution of multiwalled CNTs (MWCNTs) is reported to largely improve the electrical conductivity of biodegradable poly(l-lactide) (PLLA) through crystalline morphology development by addition of high-melting-point PLLA (hPLLA) crystallites. hPLLA crystallites are efficient nucleating agents, increasing the crystallinity and crystallization rate of PLLA/MWCNT nanocomposites. Furthermore, the diameter of spherulites decreases from 9.7 to 1.0 MUm with an increase in the concentration of hPLLA from 0.03 to 3.0 wt %. The electrical conductivity of PLLA/MWCNT nanocomposites with 0.3 wt % MWCNTs greatly increases from 1.89 * 10(-15) to 1.56 * 10(-8) S/cm with an increase in the matrix crystallinity from 2.4 to 46.8% on introducing trace amounts of hPLLA (0.07 wt %). The percolation threshold of PLLA/MWCNT nanocomposites is reduced from 0.51 to 0.21 wt % on addition of 0.07 wt % hPLLA. The high electrical conductivity and low percolation threshold of PLLA/MWCNT nanocomposites incorporated with hPLLA are related to the high crystallinity and crystalline morphologies of the PLLA matrix. Big spherulites lock a lot of MWCNTs at the intervals in the spherulites, which is harmful to the electrical conductivity. Small spherulites, with large surface areas, also need more MWCNTs to form conductive networks in the amorphous regions. Most MWCNTs that are bundled together to form conductive paths are found in samples with mid-sized spherulites of ~6.7 MUm. More interestingly, the high crystallinity and reconstructed MWCNT network also enhanced the Young modulus, elongation at break, and elastic modulus at high temperature of PLLA/MWCNT nanocomposites with small amounts of hPLLA. PMID- 27379386 TI - Predictive factors of the pharmacological action of tolvaptan in patients with liver cirrhosis: a post hoc analysis. AB - BACKGROUND: Tolvaptan has been approved in Japan for the treatment of hepatic edema. An important consideration in providing a clinical benefit to patients with liver cirrhosis is the improvement of ascites-related clinical symptoms. In the present post hoc analysis, we aimed to identify factors that were predictive of the potency of tolvaptan, and to examine the relationship between changes in initial urine volume and improvement in ascites-related clinical symptoms. METHODS: This post hoc analysis was based on three previous phase 2 and 3 clinical trials of tolvaptan in patients with liver cirrhosis. Predictive factors associated with a change in initial urine volume were identified. A change of >=500 mL from baseline confirmed the pharmacological action of tolvaptan treatment. The relationship between the change in initial urine volume and improvement in ascites-related clinical symptoms was also examined. RESULTS: A total of 152 patients were enrolled in this study. Body weight and BUN were identified as predictive parameters. Among patients with a change in initial urine volume of >=500 mL, 75 % demonstrated improvement in ascites-related clinical symptoms, while no improvement was seen in those with a change of <500 mL. None of the patients with initial urine volume of <500 mL showed resolution of symptoms. CONCLUSIONS: Change in urine volume was affected by both baseline body weight and BUN in tolvaptan-treated subjects. Higher urine output was associated with improvements in ascites-related clinical symptoms. PMID- 27379387 TI - Investigation into Host Selection of the Cecal Acetogen Population in Rabbits after Weaning. AB - Homoacetogenic bacteria have received attention as a hydrogenotrophic population that offers a significant energetic advantage to the host animal. Reductive acetogenesis is likely an important hydrogen disposal mechanism in the cecum of rabbits. However, molecular ecology information about cecal acetogen candidates has rarely been reported. To better understand the effect of host selection in the rabbit cecal acetogen community with respect to growth, rabbits at four different age stages (30, 60, 120 and 180 days) with the same diet were studied. Although the abundance of potential acetogens and methanogens was high in the cecum of rabbits undergoing growth, many novel potential acetogen populations were observed in the cecum of rabbits across all age groups. Young and adult rabbits had their own distinct acetogen community although they received the same diet, which suggests that as the rabbit ages, acetogens in the cecum undergo developmental changes because of host selection that are independent of diet, and perhaps the different acetogen communities result in different hydrogenotrophic characteristics. The within-group similarity increased with age, indicating that the acetogen community converges to a more homogeneous and stable arrangement with aging. PMID- 27379388 TI - Clinical Efficacy of Intravenous Lidocaine for Thyroidectomy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial. AB - BACKGROUND: Systemic lidocaine has analgesic and anti-inflammatory effects. The purpose of this prospective, randomized, double-blind study was to evaluate the effects of intravenous lidocaine on pain following thyroidectomy. METHODS: Fifty eight adult patients scheduled for total thyroidectomy were randomly allocated to receive a 1.5 mg/kg lidocaine bolus followed by a 2 mg/kg/h infusion during surgery, or the same volume of normal saline (control). After thyroidectomy, we evaluated postoperative pain, nausea, fentanyl consumption, frequency of pushing the button (FPB) for patient-controlled analgesia (PCA), High-sensitivity C reactive protein (hs-CRP) in serum, and patient satisfaction scores regarding the recovery process. RESULTS: Postoperative pain and nausea scores were significantly lower in the lidocaine group for the first 4 h following thyroidectomy, compared to the control group. Fentanyl consumption and FPB for the PCA were also significantly reduced in the lidocaine group for 4 h following thyroidectomy, and hs-CRP was significantly less in the lidocaine group at postoperative days 1 and 3. Furthermore, satisfaction scores were significantly higher in the lidocaine group compared to the control group. CONCLUSIONS: Intravenous lidocaine effectively reduced postoperative pain and nausea following thyroidectomy as well as improved the quality of recovery. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT01608360. PMID- 27379390 TI - Altered plasma levels of decanoic acid in colorectal cancer as a new diagnostic biomarker. AB - Colorectal cancer (CRC) is one of the most common tumors in developed countries. The five-year survival rate decreases depending on how advanced the CRC is when first diagnosed. Screening has been proven to greatly reduce mortality from colorectal cancer, but an ideal screening tool is far from being established. Here, we aimed to discover and validate early CRC biomarkers by means of an untargeted/targeted metabolomic approach. A preliminary untargeted analysis of plasma lipids performed on a small patient cohort (30 plasma samples) revealed some alterations that occurred in the presence of this tumor. In particular, medium-chain fatty acids with between six and twelve carbon atoms (C6-C12) were found to be the lipid class that showed the most marked changes upon the development of CRC. In order to evaluate the utility of this lipid class as diagnostic CRC biomarkers, a further study based on a wider cohort of patients (117 plasma samples) was performed. Using a targeted approach, these fatty acids were quantified in plasma samples by means of fast gas chromatography coupled to a time-of-flight analyzer. Plasma samples from patients with CRCs at different tumor stages were analyzed and compared to those from healthy subjects, ulcerative colitis patients, high-grade dysplasia adenoma patients, and breast cancer patients in order to test the specificity and sensitivity of these possible biomarkers. Results revealed significant differences among the considered groups in terms of their C6, C8, C10, and C12 fatty acid plasma concentrations. In particular, receiver operating characteristic (ROC) curves obtained for the C10 fatty acid gave an area under the curve of 0.8195 along with a sensitivity of 87.8 % and a specificity of 80 %, strongly suggesting that it could be a valuable early diagnostic biomarker of CRC. PMID- 27379389 TI - Regulation of the BMP Signaling-Responsive Transcriptional Network in the Drosophila Embryo. AB - The BMP signaling pathway has a conserved role in dorsal-ventral axis patterning during embryonic development. In Drosophila, graded BMP signaling is transduced by the Mad transcription factor and opposed by the Brinker repressor. In this study, using the Drosophila embryo as a model, we combine RNA-seq with Mad and Brinker ChIP-seq to decipher the BMP-responsive transcriptional network underpinning differentiation of the dorsal ectoderm during dorsal-ventral axis patterning. We identify multiple new BMP target genes, including positive and negative regulators of EGF signaling. Manipulation of EGF signaling levels by loss- and gain-of-function studies reveals that EGF signaling negatively regulates embryonic BMP-responsive transcription. Therefore, the BMP gene network has a self-regulating property in that it establishes a balance between its activity and that of the antagonistic EGF signaling pathway to facilitate correct patterning. In terms of BMP-dependent transcription, we identify key roles for the Zelda and Zerknullt transcription factors in establishing the resulting expression domain, and find widespread binding of insulator proteins to the Mad and Brinker-bound genomic regions. Analysis of embryos lacking the BEAF-32 insulator protein shows reduced transcription of a peak BMP target gene and a reduction in the number of amnioserosa cells, the fate specified by peak BMP signaling. We incorporate our findings into a model for Mad-dependent activation, and discuss its relevance to BMP signal interpretation in vertebrates. PMID- 27379392 TI - Investigations on the cell metabolomics basis of multidrug resistance from tumor cells by ultra-performance liquid chromatography-mass spectrometry. AB - Although anticancer drug resistance has been linked to high expression of P glycoprotein and the enhanced DNA repair ability, the biochemical process and the underlying mechanisms of drug resistance are not clear. In order to clarify the biochemical mechanisms of drug resistance during anticancer drug treatment, we studied the metabolomics of MCF-7/S and MCF-7/Adr cell lines, the COC1 and COC1/DDP cell lines, including the metabolic pathways of multidrug-resistant tumor cells and the changes of endogenous substances in cells. The intracellular metabolites were profiled using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In this study, 24 biomarkers in MCF-7/Adr cells and 15 biomarkers in COC1/DDP cells that are involved in some important metabolic pathways were putatively identified. Several metabolic pathways are changed in tumor cells showing drug resistance, such as protein synthesis pathways, cysteine synthesis, the glutamine metabolic pathway, and the ammonia cycle; the first of these are involved in the synthesis of some important proteins including membrane proteins, multidrug resistance-associated proteins, and P-glycoprotein (P-gp). Proteins related to drug resistance were overexpressed in multidrug-resistant tumor cells. These proteins depended on energy and play important roles in the emergence of drug resistance. The changes in glutathione and cysteine metabolic pathways showed that the cells can activate related metabolic pathways and reduce the cell apoptosis when they encounter oxidative damage. These findings indicate that drug resistance is likely associated with increased P-gp synthesis and reduced apoptosis of tumor cells. Graphical Abstract Drug resistance was charactered in the changing of genomics and proteomics. Like enhancing DNA repair, reducing uptake, high P-g protein expression. Here, we studied the changes of metabolite pathway which could be also play an imported role in drug resistance. PMID- 27379391 TI - Ultrasound-assisted dispersive liquid-liquid microextraction of tetracycline drugs from egg supplements before flow injection analysis coupled to a liquid waveguide capillary cell. AB - A simple, rapid, and efficient ultrasound-assisted dispersive liquid-liquid microextraction (US-DLLME) method was developed for extraction of tetracycline residues from egg supplement samples, with subsequent determination by flow injection analysis (FIA) coupled to a liquid waveguide capillary cell (LWCC) and a controlled temperature heating bath. Tetracyclines react with diazotized p sulfanilic acid, in a slightly alkaline medium, to form azo compounds that can be measured at 435 nm. The reaction sensitivity improved substantially (5.12-fold) using an in-line heating temperature of 45 degrees C. Multivariate methodology was used to optimize the factors affecting the extraction efficiency, considering the volumes of extraction and disperser solvents, sonication time, extraction time, and centrifugation time. Good linearity in the range 30-600 MUg L(-1) was obtained for all the tetracyclines, with regression coefficients (r) higher than 0.9974. The limits of detection ranged from 6.4 to 11.1 MUg L(-1), and the recoveries were in the range 85.7-96.4 %, with relative standard deviation lower than 9.8 %. Analyte recovery was improved by approximately 6 % when the microextraction was assisted by ultrasound. The results obtained with the proposed US-DLLME-FIA method were confirmed by a reference HPLC method and showed that the egg supplement samples analyzed were suitable for human consumption. PMID- 27379393 TI - ABC's spotlight on the nanoworld. PMID- 27379394 TI - ADMET Evaluation in Drug Discovery. 16. Predicting hERG Blockers by Combining Multiple Pharmacophores and Machine Learning Approaches. AB - Blockade of human ether-a-go-go related gene (hERG) channel by compounds may lead to drug-induced QT prolongation, arrhythmia, and Torsades de Pointes (TdP), and therefore reliable prediction of hERG liability in the early stages of drug design is quite important to reduce the risk of cardiotoxicity-related attritions in the later development stages. In this study, pharmacophore modeling and machine learning approaches were combined to construct classification models to distinguish hERG active from inactive compounds based on a diverse data set. First, an optimal ensemble of pharmacophore hypotheses that had good capability to differentiate hERG active from inactive compounds was identified by the recursive partitioning (RP) approach. Then, the naive Bayesian classification (NBC) and support vector machine (SVM) approaches were employed to construct classification models by integrating multiple important pharmacophore hypotheses. The integrated classification models showed improved predictive capability over any single pharmacophore hypothesis, suggesting that the broad binding polyspecificity of hERG can only be well characterized by multiple pharmacophores. The best SVM model achieved the prediction accuracies of 84.7% for the training set and 82.1% for the external test set. Notably, the accuracies for the hERG blockers and nonblockers in the test set reached 83.6% and 78.2%, respectively. Analysis of significant pharmacophores helps to understand the multimechanisms of action of hERG blockers. We believe that the combination of pharmacophore modeling and SVM is a powerful strategy to develop reliable theoretical models for the prediction of potential hERG liability. PMID- 27379395 TI - MRI Background Parenchymal Enhancement Is Not Associated with Breast Cancer. AB - BACKGROUND: Previously, a strong positive association between background parenchymal enhancement (BPE) at magnetic resonance imaging (MRI) and breast cancer was reported in high-risk populations. We sought to determine, whether this was also true for non-high-risk patients. METHODS: 540 consecutive patients underwent breast MRI for assessment of breast findings (BI-RADS 0-5, non-high risk screening (no familial history of breast cancer, no known genetic mutation, no prior chest irradiation, or previous breast cancer diagnosis)) and subsequent histological work-up. For this IRB-approved study, BPE and fibroglandular tissue FGT were retrospectively assessed by two experienced radiologists according to the BI-RADS lexicon. Pearson correlation coefficients were calculated to explore associations between BPE, FGT, age and final diagnosis of breast cancer. Subsequently, multivariate logistic regression analysis, considering covariate colinearities, was performed, using final diagnosis as the target variable and BPE, FGT and age as covariates. RESULTS: Age showed a moderate negative correlation with FGT (r = -0.43, p<0.001) and a weak negative correlation with BPE (r = -0.28, p<0.001). FGT and BPE correlated moderately (r = 0.35, p<0.001). Final diagnosis of breast cancer displayed very weak negative correlations with FGT (r = -0.09, p = 0.046) and BPE (r = -0.156, p<0.001) and weak positive correlation with age (r = 0.353, p<0.001). On multivariate logistic regression analysis, the only independent covariate for prediction of breast cancer was age (OR 1.032, p<0.001). CONCLUSIONS: Based on our data, neither BPE nor FGT independently correlate with breast cancer risk in non-high-risk patients at MRI. Our model retained only age as an independent risk factor for breast cancer in this setting. PMID- 27379396 TI - "Initial investigation into computer scoring of candidate essays for personnel selection": Correction to Campion et al. (2016). AB - Reports an error in "Initial Investigation Into Computer Scoring of Candidate Essays for Personnel Selection" by Michael C. Campion, Michael A. Campion, Emily D. Campion and Matthew H. Reider (Journal of Applied Psychology, Advanced Online Publication, Apr 14, 2016, np). In the article the affiliations for Emily D. Campion and Matthew H. Reider were originally incorrect. All versions of this article have been corrected. (The following abstract of the original article appeared in record 2016-18130-001.) Emerging advancements including the exponentially growing availability of computer-collected data and increasingly sophisticated statistical software have led to a "Big Data Movement" wherein organizations have begun attempting to use large-scale data analysis to improve their effectiveness. Yet, little is known regarding how organizations can leverage these advancements to develop more effective personnel selection procedures, especially when the data are unstructured (text-based). Drawing on literature on natural language processing, we critically examine the possibility of leveraging advances in text mining and predictive modeling computer software programs as a surrogate for human raters in a selection context. We explain how to "train" a computer program to emulate a human rater when scoring accomplishment records. We then examine the reliability of the computer's scores, provide preliminary evidence of their construct validity, demonstrate that this practice does not produce scores that disadvantage minority groups, illustrate the positive financial impact of adopting this practice in an organization (N ~ 46,000 candidates), and discuss implementation issues. Finally, we discuss the potential implications of using computer scoring to address the adverse impact validity dilemma. We suggest that it may provide a cost-effective means of using predictors that have comparable validity but have previously been too expensive for large-scale screening. (PsycINFO Database Record PMID- 27379397 TI - Validation of inertial measurement units with an optoelectronic system for whole body motion analysis. AB - The potential of inertial measurement units (IMUs) for ergonomics applications appears promising. However, previous IMUs validation studies have been incomplete regarding aspects of joints analysed, complexity of movements and duration of trials. The objective was to determine the technological error and biomechanical model differences between IMUs and an optoelectronic system and evaluate the effect of task complexity and duration. Whole-body kinematics from 12 participants was recorded simultaneously with a full-body Xsens system where an Optotrak cluster was fixed on every IMU. Short functional movements and long manual material handling tasks were performed and joint angles were compared between the two systems. The differences attributed to the biomechanical model showed significantly greater (P <= .001) RMSE than the technological error. RMSE was systematically higher (P <= .001) for the long complex task with a mean on all joints of 2.8 degrees compared to 1.2 degrees during short functional movements. Definition of local coordinate systems based on anatomical landmarks or single posture was the most influent difference between the two systems. Additionally, IMUs accuracy was affected by the complexity and duration of the tasks. Nevertheless, technological error remained under 5 degrees RMSE during handling tasks, which shows potential to track workers during their daily labour. PMID- 27379398 TI - Ca L2,3-edge XANES and Sr K-edge EXAFS study of hydroxyapatite and fossil bone apatite. AB - Upon burial, the organic and inorganic components of hard tissues such as bone, teeth, and tusks are subjected to various alterations as a result of interactions with the chemical milieu of soil, groundwater, and presence of microorganisms. In this study, simulation of the Ca L 2,3-edge X-ray absorption near edge structure (XANES) spectrum of hydroxyapatite, using the CTM4XAS code, reveals that the different symmetry of the two nonequivalent Ca(1) and Ca(2) sites in the unit cell gives rise to specific spectral features. Moreover, Ca L 2,3-edge XANES spectroscopy is applied in order to assess variations in fossil bone apatite crystallinity due to heavy bacterial alteration and catastrophic mineral dissolution, compared to well-preserved fossil apatite, fresh bone, and geologic apatite reference samples. Fossilization-induced chemical alterations are investigated by means of Ca L 2,3-edge XANES and scanning electron microscopy (SEM) and are related to histological evaluation using optical microscopy images. Finally, the variations in the bonding environment of Sr and its preference for substitution in the Ca(1) or Ca(2) sites upon increasing the Sr/Ca ratio is assessed by Sr K-edge extended X-ray absorption fine structure (EXAFS) spectroscopy. PMID- 27379399 TI - To attach or not to attach? The effect of carrier surface morphology and topography on attachment of phoretic deutonymphs of Uropoda orbicularis (Acari). AB - Previous studies on preferences of phoretic deutonymphs of Uropodina for attachment sites have shown that they frequently select smooth and hydrophobic surfaces. The aim of our study was to provide the detailed morphological and topographical characteristics of beetle body surfaces to which deutonymphs frequently attach and to verify how the presence of setae and surface sculpture affects deutonymph attachment. The study was conducted on Uropoda orbicularis (Muller, 1776) and its common beetle carriers: Aphodius prodromus (Brahm, 1790), Aphodius fimetarius (Linnaeus, 1758), Onthophagus nuchicornis (Linnaeus, 1758) and Margarinotus carbonarius (Hoffmann, 1803). Morphology and topography of elytra, femora, propygidia and pygidia of beetles were analysed mainly using SEM methods supported with CLSM and AFM techniques. The hypothesis that deutonymphs may attach to surfaces covered with setae, if seta density is low enough not to disturb mite movement, was tested. The study revealed that deutonymphs attach to surfaces of various types as follows: (i) smooth, (ii) hairy, i.e., covered with setae, (iii) flat and (iv) sculptured. Smooth body parts and body parts covered with setae of low density were most frequently and intensively occupied with deutonymphs. Surfaces of high seta density were avoided by mites. Within elytra of Aphodius beetles, deutonymphs definitely preferred flat surfaces of elytral intervals. On the contrary, densely punctuated propygidium and pygidium in M. carbonarius were heavily infested with deutonymphs. We conclude that carrier surface morphology and topography are important for Uropodina deutonymph attachment, but these two factors cannot fully explain the observed relation. PMID- 27379400 TI - Generation of functional hepatocyte-like cells from human deciduous periodontal ligament stem cells. AB - Human deciduous periodontal ligament stem cells have been introduced for as an easily accessible source of stem cells from dental origin. Although recent studies have revealed the ability of these stem cells in multipotential attribute, their efficiency of hepatic lineage differentiation has not been addressed so far. The aim of this study is to investigate hepatic lineage fate competence of periodontal ligament stem cells through direct media induction. Differentiation of periodontal ligament stem cells into hepatocyte-like cells was conducted by the exposure of two phase media induction. First phase was performed in the presence of hepatocyte growth factors to induce a definitive endoderm formation. In the subsequent phase, the cells were treated with oncostatin M and dexamethosone followed by insulin and transferrin to generate hepatocyte-like cells. Hepatic-related characters of the generated hepatocyte-like cells were determined at both mRNA and protein level followed by functional assays. Foremost changes observed in the generation of hepatocyte-like cells were the morphological features in which these cells were transformed from fibroblastic shape to polygonal shape. Temporal expression of hepatic markers ranging from early endodermal up to late markers were detected in the hepatocyte-like cells. Crucial hepatic markers such as glycogen storage, albumin, and urea secretion were also shown. These findings exhibited the ability of periodontal ligament stem cells of dental origin to be directed into hepatic lineage fate. These cells can be regarded as an alternative autologous source in the usage of stem cell based treatment for liver diseases. PMID- 27379401 TI - The effect of colour polymorphism on thermoregulation in an orb web spider. AB - Spiders that build aerial webs in open areas face the risk of overheating due to incident solar radiation. These spiders can counteract overheating by either moving the web to another site or by adopting behavioural thermoregulation within the web. Since moving can be costly, studies have suggested that a passive but effective method of reducing heat load is by light reflectance through body colouration. We explored the interaction between colour and thermoregulation in a colour polymorphic species, under both field and laboratory conditions. We show that in natural conditions, the spiders maintain their body temperature below that of the ambient, but with no difference in surface temperature between colour morphs. In laboratory experiments with internal temperature measurements, white morphs bore the risk of overheating better than the yellow morphs since they heated up slower and cooled faster. We suggest that the thermoregulatory properties of colour polymorphism in Verrucosa arenata have physiological consequences and may play an important role in the maintenance of colour polymorphism in this species. PMID- 27379402 TI - Population Pharmacokinetic and Covariate Analysis of Apatinib, an Oral Tyrosine Kinase Inhibitor, in Healthy Volunteers and Patients with Solid Tumors. AB - BACKGROUND AND OBJECTIVES: Apatinib is an oral tyrosine kinase inhibitor approved in China for the treatment of patients with advanced metastatic gastric cancer. The approved dosing schedule is 850 mg once daily. The objective of this study was to develop a population pharmacokinetic (popPK) model of apatinib and determine factors that affect its pharmacokinetics. METHODS: A popPK model for apatinib was developed using data from 106 individuals, including healthy volunteers and patients with malignant solid tumors. The potential influence of demographic, patient, and laboratory characteristics on oral apatinib pharmacokinetics were investigated in a covariate analysis. The extent of the impact of significant covariates on the exposure of apatinib was evaluated using simulations. RESULTS: The final popPK model was a two-compartment model with mixed first- and zero-order absorption and first-order elimination. The population estimates of apparent clearance (CL/F) and apparent volume at steady state were 57.8 L/h and 112.5 L, respectively. The non-linear dose proportionality in apatinib relative bioavailability was characterized by a sigmoidal maximum effect (E max) equation wherein the midpoint dose for the decrease in bioavailability was 766 mg. Patients with advanced gastric cancer exhibited lower bioavailability. Cancer patients in general had lower CL/F than healthy volunteers. Simulation results indicated that apatinib exposure in various population groups were impacted by disease and laboratory characteristics. CONCLUSIONS: The increase in apatinib exposure was less than proportional to dose. The pharmacokinetics of apatinib in gastric cancer patients were significantly different from those in patients with other cancer types. Dosing of apatinib in various cancer subpopulations may require adjustments to optimize efficacy and benefits to patients. PMID- 27379404 TI - Trifluoromethylthiolation and Trifluoromethylselenolation of alpha-Diazo Esters Catalyzed by Copper. AB - alpha-Diazo esters are smoothly converted into the corresponding trifluoromethyl thio- or selenoethers by reaction with Me4 NSCF3 or Me4 NSeCF3 , respectively, in the presence of catalytic amounts of copper thiocyanate. This straightforward method gives high yields under neutral conditions at room temperature and is applicable to a wide range of functionalized molecules, including diverse alpha amino acid derivatives. It is well-suited for the late-stage introduction of trifluoromethylthio or -seleno groups into drug-like molecules. PMID- 27379403 TI - Platelet-Derived Growth Factor in the Ovarian Follicle Attracts the Stromal Cells of the Fallopian Tube Fimbriae. AB - During human ovulation, the fallopian tube fimbriae must move to the ovulation site to catch the oocyte. As the tissue-of-origin of the majority of ovarian high grade serous carcinoma (HGSC), the fallopian tube fimbriae carrying a precursor cancer lesion may also approach the ovulatory site for metastasis. We hypothesize that platelet-derived growth factor (PDGF) in mature follicle fluid (FF) attracts the migration of PDGFR-expressing fimbriae toward the ovulating follicle. We observed that more PDGFR-beta was expressed in the distal part than in the proximal parts of the fallopian tube, particularly in stromal cells in the lamina propria. The stromal cells, but not the epithelial cells, from normal fimbriae and fallopian tube HGSC were highly chemotactic to mature FF. The chemotactic activities were positively correlated with PDGF-BB and estradiol levels in FF and were abolished by a blocking antibody of PDGFR-beta and by tyrosine kinase inhibitor imatinib. When PDGF-BB/AB was depleted from the FF, more than 80% of chemotaxis activities were diminished. This study suggests an ovarian follicle directed and PDGF-dependent attraction of fallopian tube fimbriae before ovulation. The same mechanism may also be crucial for the ovarian homing of HGSC, which largely originates in the fimbriae. PMID- 27379406 TI - Three-year trajectories of global perceived quality of life for youth with chronic health conditions. AB - PURPOSE: Objectives of this longitudinal study were to examine 3-year trajectories of global perceived quality of life (QOL) for youth with chronic health conditions, as obtained from youth and parent reports, and to identify personal and environmental factors associated with the trajectory groups for each perspective. METHODS: Youth with various chronic conditions aged 11-17 years and one of their parents were recruited from eight children's treatment centers. Latent class growth analysis was used to investigate perceived QOL trajectories (separately for youth and parent perspectives) over a 3-year period (four data collection time points spaced 12 months apart). Multinomial logistic regression was employed to identify factors associated with these trajectories. RESULTS: A total of 439 youth and one of their parents participated at baseline, and 302 (69 %) of those youth/parent dyads completed all four data collection time points. Two QOL trajectories were identified for the youth analysis: 'high and stable' (85.7 %) and 'moderate/low and stable' (14.3 %), while three trajectories were found for the parent analysis: 'high and stable' (35.7 %), 'moderate and stable' (46.6 %), and 'moderate/low and stable' (17.7 %). Relative to the 'high and stable' groups, youth with more reported pain/other physical symptoms, emotional symptoms, and home/community barriers were more likely to be in the 'moderate and stable' or 'moderate/low and stable' groups. Also, youth with higher reported self-determination, spirituality, family social support, family functioning, school productivity/engagement, and school belongingness/safety were less likely to be in the 'moderate and stable' or 'moderate/low and stable' groups, compared to the 'high and stable' groups. CONCLUSION: Findings suggest that youth with chronic conditions experience stable global perceived QOL across time, but that some individuals maintain stability at moderate to moderate/low levels which is related to ongoing personal and environmental influences. Potential benefits of universal strategies and programs to safeguard resilience for all youth and targeted interventions to optimize certain youths' global perceived QOL are indicated. PMID- 27379405 TI - QOL and sociodemographic factors among first-time parents in Japan: a multilevel analysis. AB - PURPOSE: The present study aimed to examine the relationship between sociodemographic factors and domains of quality of life (QOL) among married adults in Japan who were either rearing or expecting their first child. Our research focus was on whether different sociodemographic variables interacted with each other in predicting the first-time parents' QOL. METHOD: In total, 4374 (mean age = 34.9 years, SD = 8.4, range 18-71) community-based married couples pooled from two surveys provided their sociodemographic information (i.e., age, years of education, and annual income) and responded to the brief version of the QOL instrument developed by the World Health Organization (WHOQOL-BREF in Psychological Medicine 28(3):551-555, 1998). RESULTS: Series of multilevel regression analyses revealed that household annual income and education were associated with all domains of QOL, and other sociodemographic variables worked in a domain-specific manner. In addition, the effect of educational attainment on psychological domain was significant for mothers only, whereas the effects of household income on psychological and environmental domains were stronger for the younger (below age 26) than the older (over 43) couples. CONCLUSION: The effects of sociodemographic factors at couple as well as individual levels on the first time parents' QOL were examined for the first time in Japan using couple data. In addition to corroborating previous findings on the main effects concerning these variables, the present study demonstrated the complex patterns of interaction across different levels. These findings provide evidence for the need for financial and health measures targeted at specific parent populations. PMID- 27379407 TI - Simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell cultures and in sub-regions of guinea pig brain. AB - In the present paper, we describe a validated chromatographic method for the simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell culture and in sub-regions of the guinea pig brain. Electrochemical detection provided limits of quantifications (LOQs) between 3.6 and 12nM. Within the linear range, obtained recoveries were from 90.9+/-9.9 to 120+/-14% and intra-day and inter-day precisions found to be less than 5.5% and 12%, respectively. The analytical method was applicable for quantification of intracellular and extracellular amounts of monoamine neurotransmitters and their metabolites in guinea pig frontal cortex and hippocampal primary neuronal cell cultures. Noradrenaline, dopamine and serotonin were found to be in a range from 0.31 to 1.7pmol per 2 million cells intracellularly, but only the biogenic metabolites could be detected extracellularly. Distinct differences in monoamine concentrations were observed when comparing concentrations in guinea pig frontal cortex and cerebellum tissue with higher amounts of dopamine and its metabolites, 3,4 dihydroxyphenylacetic acid and homovanillic acid in frontal cortex, as compared to cerebellum. The chemical turnover in frontal cortex tissue of guinea pig was for serotonin successfully predicted from the turnover observed in the frontal cortex cell culture. In conclusion, the present analytical method shows high precision, accuracy and sensitivity and is broadly applicable to monoamine measurements in cell cultures as well as brain biopsies from animal models used in preclinical neurochemistry. PMID- 27379408 TI - Investigating Female Sexual Concordance: Do Sexual Excitation and Sexual Inhibition Moderate the Agreement of Genital and Subjective Sexual Arousal in Women? AB - The agreement of subjective and genital sexual response, also referred to as sexual concordance, shows substantial variability between women. Identifying predictors of sexual arousal and sexual concordance is important to improve our understanding of female sexual response and its relationship to sexual function or dysfunction. The aim of this study was to assess the relevance of sexual excitation and sexual inhibition as predictors of subjective sexual arousal, genital arousal, and sexual concordance. In a laboratory setting, sexual arousal was induced by erotic video stimuli. Subjective sexual arousal was assessed continuously during stimulus presentation and genital arousal was measured with vaginal photoplethysmography. Data of 58 women (M age = 24.95, SD = 4.65) were analyzed using multilevel analyses (HLM). This data analytic technique estimates the within-subject associations of subjective and genital arousal, by controlling for between-subject differences. An interaction term of sexual excitation and sexual inhibition significantly predicted genital sexual arousal. In exploratory analyses, two lower order factors of sexual inhibition (Concerns about Sexual Function and Arousal Contingency) were predictive of sexual concordance. Further examination of these associations might increase our knowledge of female sexual function and deepen our understanding of how sexual excitation and sexual inhibition affect sexual arousal and consequently, impact sexual behaviors, in women. PMID- 27379409 TI - 2 or 5? PMID- 27379410 TI - Camellia nanningensis sp. nov.: the earliest fossil wood record of the genus Camellia (Theaceae) from East Asia. AB - A new species Camellia nanningensis was described on the basis of well-preserved mummified wood from the upper Oligocene Yongning Formation of Nanning Basin in Guangxi Province, South China. This represents the most ancient fossil wood assigned to Camellia, and the earliest fossil record of the family Theaceae in China. This fossil material shows that Camellia occurred in China as early as the late Oligocene, suggesting more ancient radiation of this genus than estimated by molecular dating. PMID- 27379411 TI - Characteristics of Synthetic Cannabinoid and Cannabis Users Admitted to a Psychiatric Hospital: A Comparative Study. AB - BACKGROUND: Psychotic and affective exacerbations associated with synthetic cannabinoid (SC) use are becoming an emerging concern in psychiatric hospitals. However, data are lacking regarding whether clinical manifestations of SC use differ from those associated with cannabis use. OBJECTIVE: Our aim was to explore the unique profile of SC users admitted to a mental health center in terms of demographic, clinical, and physiologic variables in comparison to cannabis users. METHODS: We retrieved retrospective data of patients admitted to a mental health center between October 2007 and May 2014 who self-reported recent use of SC (n = 60) and patients who were cannabis users (positive carboxy-tetrahydrocannabinol urine test at admission) without a history of SC use (n = 163). Clinical measures included hospitalization length, number of previous hospitalizations, Positive and Negative Syndrome Scale (PANSS) scores, psychiatric status at admission, and relevant physiologic and laboratory parameters. RESULTS: Hospitalized SC users were younger than hospitalized cannabis users (n = 163) (30.46 +/- 7.83 years versus 34.67 +/- 10.07 years, U223 = 3,781.5, P = .009, respectively). SC patients had longer hospitalizations compared to cannabis users (43.45 +/- 54.02 days versus 22.91 +/- 31.36 days, U219 = 5,701.5, P = .005, respectively), had more previous hospitalizations (3.73 +/- 5.05 versus 1.98 +/- 5.12, U223 = 6,284, P < .001, respectively), and were more likely to be hospitalized by criminal court order (36.7% [n = 22] versus 19.9% [n = 32], chi22 = 7.136, P = .028, respectively). SC patients presented with a more severe clinical picture manifested by higher total PANSS scores (82.53 +/- 23.05 versus 69.98 +/- 19.94, t91 = -2.696, P = .008) in a subset of patients with PANSS scores assessed within a week from admission (n = 30 in the SC group and n = 63 in the cannabis group). No differences were found in physiologic or laboratory measures on admission between the SC and cannabis groups. CONCLUSIONS: Patients admitted following use of SC are generally younger males who have higher severity of psychotic symptoms at admission, are more likely to be admitted by criminal court order, and require longer hospitalization periods in comparison to cannabis users. PMID- 27379412 TI - Beyond the Parental Generation: The Influence of Grandfathers and Great grandfathers on Status Attainment. AB - Studies on intergenerational social mobility usually examine the extent to which social positions of one generation determine the social positions of the next. This study investigates whether the persistence of inequality can be expected to stretch over more than two generations. Using a multigenerational version of GENLIAS, a large-scale database containing information from digitized Dutch marriage certificates during 1812-1922, this study describes and explains the influence of grandfathers and great-grandfathers on the occupational status attainment of 119,662 men in the Netherlands during industrialization. Multilevel regression models show that both grandfather's and great-grandfather's status influence the status attainment of men, after fathers and uncles are taken into account. Whereas the influence of the father and uncles decreases over time, that of the grandfather and great-grandfather remains stable. The results further suggest that grandfathers influence their grandsons through contact but also without being in contact with them. Although the gain in terms of explained variance from using a multigenerational model is moderate, leaving out the influence of the extended family considerably misrepresents the influence of the family on status attainment. PMID- 27379413 TI - Decompressive Hemicraniectomy in Malignant Middle Cerebral Artery Infarction: The 'Real World' Beyond Studies. AB - BACKGROUND: Decompressive hemicraniectomy (DHC) is life-saving in patients with malignant middle cerebral artery infarction (MMI), but outcome, perspectives and complications after DHC in daily practice are largely unknown. METHODS: From 2008 until 2014, we extracted patient's characteristics as well as complications from our database for patients with MMI who underwent DHC. Additionally, we analysed medical records from the different rehabilitation steps. RESULTS: We identified 48 consecutive patients (mean 57 years, 21 male, 41.7% >60 years) with MMI who underwent DHC. The decision for DHC was made on an individual basis, including patients without impaired consciousness or stroke onset >48 h. In-hospital patients achieved only marginal clinical improvement. Seventy-five percent attended an early-rehabilitation, 44% achieved post-stroke rehabilitation and 6% carried on late-stage rehabilitation. In all, 45.5% returned home after rehabilitation. In-hospital mortality was 14.6%, overall mortality was 16.7%. Surviving patients (78.9%) had a modified Rankin Scale of 4-5. Frequent neurologic complications were symptomatic epilepsy and delirium. Following DHC/bone-flap-reimplantation, wound-healing disorders, epidural hematoma and wound infections were major surgery-related complications. Pulmonary infections were frequent in the acute-phase and urinary tract infections were predominant in the late-phase. CONCLUSIONS: DHC is a life-saving technique in patients with MMI, but complications are frequent, were underestimated in randomized clinical trials and may worsen the functional outcome. PMID- 27379414 TI - Circulating miR-30 is related to carotid artery atherosclerosis. AB - OBJECTIVES: The aim of this study is to evaluate the relationship of miR-30 with office and ambulatory blood pressure parameters and carotid intima-media thickness (CIMT) in patients with hypertension and healthy controls. METHODS: We assessed the expression level of miR-30 in 40 patients with essential hypertension and 40 healthy individuals. All patients underwent carotid artery ultrasonography, and office and ambulatory blood pressure monitoring. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to evaluate the expression level of selected miR-30. The miR-30 expression level correlation between blood pressure parameters and CIMT was assessed using the Spearman correlation coefficient. Multiple logistic regression analysis was performed to assess independent association between miR-30 expression level and CIMT. RESULTS: We observed lower expression level of miR-30 (26.01 +/- 2.40 vs. 28.26 +/- 1.28; p < 0.001) in hypertensive patients compared with healthy control individuals, as well as in increased CIMT group compared with normal CIMT group (25.09 +/- 1.84 vs. 27.81 +/- 2.37; p < 0.001). miR-30 expression level showed significant negative correlation with 24 h mean SBP (r = -0.51, p < 0.001), 24 h mean DBP(r = -0.316, p = 0.004), office SBP(r = -0.502, p < 0.001), office DBP (r = -0.205, p = 0.068), and CIMT (r = -0.578, p < 0.001), respectively. The odds ratio for CIMT was 0.519 (B = -0.748, CI 95% 0.278, 0.806; p = 0.006). CONCLUSION: Our study suggests that circulating miR-30 might be used as a biomarker for atherosclerosis in essential hypertensive patients. PMID- 27379415 TI - Effect of Size and Structure on the Ground-State and Excited-State Electronic Structure of TiO2 Nanoparticles. AB - We investigated the influence of size and structure on the electronic structure of TiO2 nanoparticles 0.5-3.2 nm in diameter, in both vacuum and water, using density functional theory (DFT) calculations. Specifically, we tracked the optical and electronic energy gap of a set of (TiO2)n nanoparticles ranging from small non-bulklike clusters with n = 4, 8, and 16, to larger nanoparticles derived from the anatase bulk crystal with n = 35 and 84. As the difference between these two energy gaps (the exciton binding energy) becomes negligible in the bulk, this magnitude provides an indicator of the bulklike character of the electronic structure of the nanoparticles under study. Extrapolating our results to larger sizes, we obtain a rough estimate of the nanoparticle size at which the electronic structure will begin to be effectively bulklike. Our results generally confirmed that the electronic structure of the nanoparticle ground state and excited state has a more pronounced structure dependency than size dependency within a size range of 0.5-1.5 nm. We also showed that the thermodynamic preference for the photocatalytic species is the first S1 exciton. This S1 exciton is stable under vacuum but may evolve to free charge carriers upon structural relaxation in an aqueous environment for particles 0.5-1.5 nm in size studied in the present article. An analysis of ionization potentials and electron affinities, relative to the standard reduction potential for the water splitting half-reactions, revealed the importance of considering the structural relaxation in the excited states and the presence of water for assessing the thermodynamic conditions for photocatalytic water splitting. PMID- 27379416 TI - Frailty Index as a Predictor of Adverse Postoperative Outcomes in Patients Undergoing Cervical Spinal Fusion. AB - STUDY DESIGN: Retrospective study of prospectively collected data. OBJECTIVE: To investigate the applicability of the modified frailty index (mFI) as a predictor of adverse postoperative events in patients undergoing anterior cervical discectomy and fusion (ACDF) or posterior cervical fusion (PCF). SUMMARY OF BACKGROUND DATA: Prior studies have investigated the mFI and shown it as an independent predictor of adverse postoperative outcomes across multiple surgical specialties. However, this topic has not still been studied in patients undergoing cervical fusion or in spinal surgery. METHODS: The National Surgical Quality Improvement Program is a multicenter clinical registry that prospectively collects preoperative risk factors, intraoperative variables, and 30-day postoperative morbidity and mortality outcomes from about 400 hospitals nationwide. Current Procedural Terminology codes were used to query the database for adults who underwent elective ACDF and PCF between 2005 and 2012. The mFI was calculated for each patient. Univariate analysis and multivariate logistic regression were used to analyze the mFI as a predictor for postoperative complications. RESULTS: For ACDF group, Clavien-Dindo grade IV complications rate increased from 0.8% to 9.0% as mFI increased from 0 to >=0.27, and mFI = 0.27 was found to be an independent predictor of Clavien-Dindo grade IV complications (odds ratio, OR, = 4.67, 95% confidence interval, CI, = 2.27-9.62, P < 0.001). For PCF groups, Clavien-Dindo grade IV complications rate increased from 0.7% to 20.0% as mFI increased from 0 to >=0.36, and mFI >= 0.36 was identified as an independent predictor of Clavien-Dindo grade IV complications (OR = 41.26, 95% CI = 6.62-257.15, P < 0.001). CONCLUSION: The mFI was shown to be an independent predictor of Clavien-Dindo grade IV complications in patients undergoing ACDF or PCF. The mFI itself may be used to stratify risks in patients undergoing cervical fusion, or, the mFI scheme could be used as a platform upon which more efficient risk stratification could be done with addition of other variables. LEVEL OF EVIDENCE: 4. PMID- 27379417 TI - Underlying Anatomy and Typing Diagnosis of May-Thurner Syndrome and Clinical Significance: An Observation Based on CT. AB - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To explore the underlying anatomy of May-Thurner syndrome (MTS) using computed tomography (CT) and discuss its clinical significance for typing diagnosis. SUMMARY OF BACKGROUND DATA: Because the anatomical position of the corpse cannot fully illustrate the actual clinical situation in vivo, the diversity of MTS has not been fully elucidated yet. METHODS: We retrospectively analyzed the data of 69 patients with MTS. By CT showing, patients were categorized to simple MTS (sMTS, 22 patients), lumbar degeneration-related MTS (dMTS, 33 patients) and other causes MTS (oMTS, 14 patients); meanwhile, a healthy control group were set. Evaluated indexes were onset age, course of disease, diameter of the iliac vein tunnel (IVTD), lumbar degeneration-related iliac vein compression (IVC), therapeutic effect, and diagnostic cutoff of risk IVTD prone to MTS. RESULTS: The onset age of sMTS, dMTS, and oMTS were respectively 42.3 +/- 6.5 years, 61.5 +/- 10.6 years, and 53.1 +/- 16.8 years (P < 0.001); courses were respectively 12.1 +/- 9.2 days, 22.5 +/- 7.6 days, and 6.8 +/- 6.7 days (P = 0.002). IVTDs of sMTS, dMTS, oMTS, and the control were respectively 2.52 +/- 0.50 mm, 2.29 +/- 0.30 mm, 5.93 +/- 2.21 mm, and 4.34 +/- 1.61 mm (P < 0.001). Lumbar degeneration-related IVC in dMTS occurred at 41 places, including forward bulging or protruding intervertebral discs (51%,17/33), osteophytes (50%,16/33), and spondylolisthesis (19%, 8/33), but none happened in sMTS, oMTS, and the control. Eighty-six percent of sMTSs, 55% dMTSs, and none oMTSs needed intravenous stent-implanted operation to obtain effective treatment. MTS type (Waldchi = 6.092, P = 0.009), course (Waldchi = 4.618, P = 0.032), and treatment plan (Waldchi = 14.748, P < 0.001) markedly influence the therapeutic result. The cutoff of risk IVTD for sMTS and dMTS was 2.98 mm, which diagnostic sensitivity was 90% and specificity 100%. CONCLUSION: Owing to the distinct pathoanatomy and causes, diagnosis in classification of MTS by CT is helpful in accurate treatment program. LEVEL OF EVIDENCE: 3. PMID- 27379419 TI - In Vivo Characteristics of Nondegenerated Adjacent Segment Intervertebral Foramina in Patients With Degenerative Disc Disease During Flexion-Extension. AB - STUDY DESIGN: In vivo patient biomechanical study. OBJECTIVE: To investigate the dimensions of lumbar intervertebral foramen (LIVF) of patients with degenerative disc disease (DDD) during a flexion-extension motion of the body. SUMMARY OF BACKGROUND DATA: LIVF narrowing may result in nerve root compression. The area changes of degenerated and adjacent nondegenerated LIVFs in DDD patients under physiologic loading conditions are unknown. METHODS: Nine symptomatic low back pain patients with radiological evidence of L4-S1 DDD were recruited. Each subject was magnetic resonance imaging scanned for construction of three dimensional lumbar vertebral models, and fluoroscopically imaged when the body extended from 45 flexion to full extension for reconstruction of LIVF dimensions. The data of the adjacent segment L3/4 and diseased segments L4/5 and L5/S1 were compared with a normal control group at 45 flexion, upright, and full extension of the body. RESULTS: The mean LIVF areas of DDD segments were significantly smaller than those of the normal subjects in all positions (P <0.05). In upright position, the LIVF areas of the DDD patients were 32.8% and 33.6% smaller than the normal subjects for L4/5 and L5/S1, respectively. For the adjacent L3/4, the LIVF area of the DDD patients was 32.3% smaller than that of the normal controls (P <0.05). The total change of L3/4 LIVF area in DDD patients from flexion to extension was significantly smaller than that of the normal subjects, but the changes in L4/5 and L5/S1 LIVF areas were similar between the two groups (P >0.05). CONCLUSION: Similar reductions of the LIVF dimensions were observed at the adjacent and the involved levels of the DDD patients, implying that biomechanical changes might have already occurred at the adjacent segment despite the lack of radiographic evidence of degeneration. Subsequent research should focus on the effects of surgical fusion on the biomechanical features of the adjacent segment. LEVEL OF EVIDENCE: N/A. PMID- 27379422 TI - Authors reply to Letter to the Editor-In response to: "Ersan I, Kilic S, Arikan S, et al. Evaluation of macular ganglion cell-inner plexiform layer and choroid in psoriasis patients using enhanced depth imaging spectral domain optical coherence tomography". PMID- 27379421 TI - Role of PKCdelta in Enhanced Expression of Gqalpha/PLCbeta1 Proteins and VSMC Hypertrophy in Spontaneously Hypertensive Rats. AB - Gqalpha signaling has been implicated in cardiac hypertrophy. In addition, angiotensin II (Ang II) was also shown to induce its hypertrophic effect through Gqalpha and PKCdelta activation. We recently showed the role of enhanced expression of Gqalpha/PLCbeta1 proteins in vascular smooth muscle cell (VSMC) hypertrophy, however, the role of PKCdelta in VSMC hypertrophy in animal model is still lacking. The present study was therefore undertaken to examine the role of PKCdelta and the associated signaling mechanisms in VSMC hypertrophy using 16 week-old spontaneously hypertensive rats (SHR). VSMC from 16-week-old SHR exhibited enhanced phosphorylation of PKCdelta-Tyr311 and increased protein synthesis, marker of hypertrophy, as compared to WKY rats which was attenuated by rottlerin, an inhibitor of PKCdelta. In addition, knocking down of PKCdelta by PKCdelta-siRNA also attenuated enhanced protein synthesis in VSMC from SHR. Furthermore, rottlerin attenuated the increased production of superoxide anion, NAD(P)H oxidase activity, increased expression of Gqalpha, phospholipase C (PLC)beta1, insulin like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) proteins in VSMC from SHR. In addition, the enhanced phosphorylation of c-Src, PKCdelta-Tyr311, IGF-1R, EGFR and ERK1/2 exhibited by VSMC from SHR was also attenuated by rottlerin. These results suggest that VSMC from SHR exhibit enhanced activity of PKCdelta and that PKCdelta is the upstream molecule of reactive oxygen species (ROS) and contributes to the enhanced expression of Gqalpha and PLCbeta1 proteins and resultant VSMC hypertrophy involving c-Src, growth factor receptor transactivation and MAP kinase signaling. PMID- 27379423 TI - L1 splitting rules in survival forests. AB - The log-rank test is used as the split function in many commonly used survival trees and forests algorithms. However, the log-rank test may have a significant loss of power in some circumstances, especially when the hazard functions or when the survival functions cross each other in the two compared groups. We investigate the use of the integrated absolute difference between the two children nodes survival functions as the splitting rule. Simulations studies and applications to real data sets show that forests built with this rule produce very good results in general, and that they are often better compared to forests built with the log-rank splitting rule. PMID- 27379424 TI - Amplifying Health Through Community Gardens: A Framework for Advancing Multicomponent, Behaviorally Based Neighborhood Interventions. AB - The article presents a framework for understanding the relationship between community garden participation, and the myriad ways gardens and participation lead to emotional, social, and health impacts. Existing empirical research relating community gardens to health behaviors, such as physical activity and diet, and longer-term chronic disease-related outcomes is summarized. The research areas discussed include the effects of community garden participation on individual, social, emotional, and environmental processes; health behaviors including diet and physical activity; and health outcomes such as self-rated health, obesity, and mental health. Other mechanisms through which community gardens may affect population health are described. Applying a multitheoretical lens to explore associations between community garden participation and health enables us to delineate key aspects of gardening that elicit positive health behaviors and multifactorial health assets that could be applied to designing other types of health interventions. PMID- 27379425 TI - Long-term prospective assessment of shoulder function after breast reconstruction involving a latissimus dorsi muscle flap transfer and postoperative radiotherapy. AB - BACKGROUND: Several investigators have evaluated the impaired function of the shoulder after removal of the latissimus dorsi muscle for breast reconstruction. However, a few investigators have studied whether including radiotherapy has a negative effect on functional recovery of the shoulder by a long-term follow-up after surgery. In this study, we compared objective measurements of shoulder function preoperatively and postoperatively for 3 years after latissimus dorsi muscle (LDM) flap transfer and postoperative radiotherapy (PRT). METHODS: Eighteen patients who underwent unilateral transfer of a pedicled LDM flap and PRT within 2 months of breast-conserving surgery were enrolled in this study. Range of motion (ROM) and muscle strength in exhaustive shoulder movements were measured before surgery, and at 3 and 6 months, and 1 and 3 years. RESULTS: The results of ROM measurements at 3months postsurgery showed significant decreases in both flexion and abduction by 7.1 and 9.2 % and at 3 years postsurgery by 4.7 and 5.7 %. The muscle strength measurements at 3 months postsurgery showed statistically significant decreases both in adduction and in the 2nd medial rotation by 30.7 and 25.9 % and at 3 years postsurgery by 36.4 and 20.4 %. A significant improvement in these impairments was not observed for 3 years after surgery compared with that at 3 months after surgery. CONCLUSION: A combination of the LDM flap procedure and PRT could be associated with a higher incidence of tissue adhesions in both flexion and abduction and muscle deficit both in adduction and in the 2nd medial rotation. PMID- 27379427 TI - [Not Available]. PMID- 27379426 TI - Letter to the Editor: regarding "Lipomatous ependymoma: report of a rare differentiation pattern with a comprehensive review of literature". PMID- 27379428 TI - [Not Available]. PMID- 27379429 TI - Correction: A Seroepidemiological Study of Serogroup A Meningococcal Infection in the African Meningitis Belt. AB - [This corrects the article DOI: 10.1371/journal.pone.0147928.]. PMID- 27379430 TI - Suberoylanilide Hydroxamic Acid Restores Estrogen Reduced-cTnI Expression in Neonatal Hearts of Mice. AB - Diastolic cardiac dysfunction can be caused by abnormality in cTnI expression during cardiogenesis. In this study, we investigated the effects of estrogen on the abnormal expression of cTnI in the hearts of neonatal mice and its potential epigenetic mechanisms. We then evaluated suberoylanilide hydroxamic acid (SAHA), a HDAC inhibitor, as a new target treatment of diastolic cardiac dysfunction. Postnatal day 0.5 C57BL/6 mice were injected with estrogen for 1 week, then the hearts of 7-day-old neonatal mice were retrieved for examination. The activities of HDAC and HAT were assayed by colorimetry, and the interaction of cTnI with HDAC5 in mice hearts were examined using chromatin immunoprecipitation assays. The expression of cTnI was tested by quantitative real-time RT-PCR and Western blot. Estrogen treated groups displayed a significantly increased HDAC activity in the hearts of neonatal mice while HAT activity remained unchanged. Additionally, HDAC5 was higher at the cTnI promoter, as compared to the saline treated control groups. The acetylation of histone H3K9ac on cTnI promoter significantly decreased in the hearts of neonatal mice treated with estrogen, and the expression of cTnI at transcriptional and protein levels also decreased. SAHA was shown to increase the acetylation of histone H3K9ac and upregulate the expression of cTnI. The data demonstrated that SAHA can correct cTnI expression abnormality caused by estrogen through inhibiting the binding of HDAC5 to the promoter of cTnI. J. Cell. Biochem. 117: 2377-2384, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27379431 TI - Processing and characteristics of canola protein-based biodegradable packaging: A review. AB - Interest increased recently in manufacturing food packaging, such as films and coatings, from protein-based biopolymers. Among various protein sources, canola protein is a novel source for manufacturing polymer films. It can be concentrated or isolated by aqueous extraction technology followed by protein precipitation. Using this procedure, it was claimed that more than 99% of protein was extracted from the defatted canola meal, and protein recovery was 87.5%. Canola protein exhibits thermoplastic properties when plasticizers are present, including water, glycerol, polyethylene glycol, and sorbitol. Addition of these plasticizers allows the canola protein to undergo glass transition and facilitates deformation and processability. Normally, canola protein-based bioplastics showed low mechanical properties, which had tensile strength (TS) of 1.19 to 4.31 MPa. So, various factors were explored to improve it, including blending with synthetic polymers, modifying protein functionality through controlled denaturation, and adding cross-linking agents. Canola protein-based bioplastics were reported to have glass transition temperature, Tg, below -50 degrees C but it highly depends on the plasticizer content. Canola protein-based bioplastics have demonstrated comparable mechanical and moisture barrier properties compared with other plant protein-based bioplastics. They have great potential in food packaging applications, including their use as wraps, sacks, sachets, or pouches. PMID- 27379434 TI - Acute-on-Chronic Liver Failure in Children: A Separate Clinical Entity. PMID- 27379432 TI - Serum Lipid Profile, Prevalence of Dyslipidaemia, and Associated Risk Factors Among Northern Mexican Adolescents. AB - BACKGROUND: The increase in overweight and obese children and adolescents may be linked to increased rates of dyslipidaemia. The aim was to assess the serum lipid profile, the prevalence of dyslipidaemia, and associated risk factors among the North Mexican adolescent population. METHODS: Two hundred and ninety-three subjects (47.8% girls) ages 11 to 16 years took part in the Nuevo Leon State Survey of Nutrition and Health 2011-2012. According to the 2011 Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents, dyslipidaemia was defined as a presence of >=1 of the following levels (mg/dL): Total cholesterol >=200, low-density lipoprotein cholesterol >=130, non-high-density lipoprotein cholesterol <40, and triglyceride >=130. RESULTS: The overall frequency of dyslipidaemia was 48.8% with no differences between sexes. Adolescents with high body mass index were more likely to have at least 1 abnormal lipid level (overweight: odds ratio [OR]: 2.07; 95% confidence interval [CI]: 1.14-3.77, P < 0.05; obesity: OR: 2.21, 95% CI: 1.11-4.41, P < 0.05) than those with normal weight. Abdominally subjects with obesity were also more likely to have at least 1 abnormal lipid level (OR: 2.30; 95% CI: 1.35-3.91, P < 0.01) than their leaner counterparts. CONCLUSIONS: Half of Mexican adolescents living in the State of Nuevo Leon have at least 1 abnormal lipid concentration. Low HDL-chol level was the most common dyslipidaemia. Body mass index and abdominal obesity were associated with the prevalence of at least 1 abnormal lipid level. PMID- 27379435 TI - Secondary metabolites from marine-derived Streptomyces antibioticus strain H74 21. AB - A new secondary metabolite, (2S,3R)-l-threonine, N-[3-(formylamino)-2 hydroxybenzoyl]-ethyl ester (streptomyceamide C, 1), together with four known compounds 1, 4-dimethyl-3-isopropyl-2,5-piperidinedione (2), cyclo-((S)-Pro-8- hydroxy-(R)-Ile (3), cyclo-((S)-Pro-(R)-Leu (4), and seco-((S)-Pro-(R)-Val) (5), were isolated from the EtOH extract of the fermented mycelium of the marine derived streptomycete strain H74-21, which was isolated from sea sediment in a mangrove site. The structure of the new compound was established on the basis of its spectroscopic data, including 1D and 2D NMR, HR-TOF-MS. Their antifungal activities against Candida albicans and cytotoxicities against human breast adenocarcinoma cell line MCF-7, human glioblastoma cell line SF-268 and human lung cancer cell line NCI-H460 were tested. Compounds 1 only displayed cytotoxicity against human breast adenocarcinoma cell line MCF-7 with the IC50 value of 27.0 MUg/mL. However, compounds 1-5 do not show antifungal activities at the test concentration of 1 mg/mL, and 2-5 have no cytotoxicities at the test concentration of 50 MUg/mL. PMID- 27379437 TI - Late stent thrombosis after the use of a bioresorbable vascular scaffold for the treatment of in-stent restenosis. PMID- 27379436 TI - Chemotherapy use and adoption of new agents is affected by age and comorbidities in patients with metastatic colorectal cancer. AB - BACKGROUND: The treatment of metastatic colorectal cancer (mCRC) has changed substantially in the last 2 decades, but to the authors' knowledge, the effect of age and comorbidities on chemotherapy use has not been well studied to date. METHODS: Patients with mCRC who were being treated with 5-fluorouracil (5-FU) based chemotherapy between January 1995 to December 2009 were studied using the LifeLink Health Plan Claims Database. The cohort was divided into older (aged >70 years) and younger (aged <=70 years) patients. The Charlson Comorbidity Index (CCI) was used to assess comorbidity burden. The Wilcoxon and chi-square tests were used in univariate and logistic regression in multivariate analyses. RESULTS: A total of 16,087 patients were identified, with 24% of the patients who were receiving chemotherapy being aged >70 years. The percentage of patients with a CCI >1 receiving chemotherapy increased over time (14% in 1996 vs 40% after 2004; P<.05). Older patients were less likely to receive treatment with >2 agents compared with younger patients (15% vs.22% and 11% vs.16%, respectively, in 2003 and 2009; P<.001). After approval by the US Food and Drug Administration in 1998, the use of irinotecan was lower in older compared with younger patients, a difference that resolved by 2002 (15% vs 38% [P<.05]; 62% in both groups [P = .9], respectively). Similarly, oxaliplatin was used more frequently in younger patients in 2003 (22% vs 15%; P<.05), with a decrease in this difference noted by 2009 (64% vs 60%; P = .95). On multivariate analysis, older age (odds ratio, 0.65; P<.001) and a CCI >1 (odds ratio, 0.84; P<.001) were found to be associated with a lower likelihood of receiving combination chemotherapy. CONCLUSIONS: In this commercially insured population, the percentage of older patients treated for mCRC was low, and the rate of chemotherapy adoption was found to lag behind that of younger patients. However, the percentage of older patients with comorbidities receiving therapy increased over time. Cancer 2016;122:3191-8. (c) 2016 American Cancer Society. PMID- 27379438 TI - Review of gynecologic and reproductive care for women with developmental disabilities. AB - PURPOSE OF REVIEW: Care for women with developmental disabilities requires special consideration for unique needs related to their cognitive and physical abilities. These women and their caregivers require more support and guidance during reproductive health care. We review the literature and provide expert opinion surrounding gynecological issues for women with developmental disabilities to support healthcare providers better understand and care for this population. RECENT FINDINGS: Women with developmental disabilities are more vulnerable to abuse and experience poorer gynecological healthcare outcomes. Many women with developmental disabilities are fertile and participate in sexual activity without adequate knowledge. They are at higher risk of pregnancy and birth complications. They are less likely to receive appropriate preventive screening. SUMMARY: The review highlights important issues and practice suggestions related to the reproductive health care of women with developmental disabilities. Topics include clinic visits, menstruation, sexuality, sexual abuse, sexual health education, contraception, sexually transmitted infections, pregnancy, labor and delivery, and cancer screening/prevention. We emphasize the need for an individualized, comprehensive approach for these patients and review perceived and actual barriers to care. More education is needed on the aforementioned topics for women with developmental disabilities, their caregivers, and their providers. PMID- 27379439 TI - The urinary microbiota: a paradigm shift for bladder disorders? AB - PURPOSE OF REVIEW: A resident microbial community [the female urinary microbiota (FUM)] exists within the female bladder of many adult women. Information about the FUM is likely to modify the diagnosis, prevention and treatment of adult women with urinary disorders. This review highlights key findings from recent literature relevant to adult, nonpregnant women. RECENT FINDINGS: Similar to other human microbial communities, the FUM varies in its characteristics, including organism diversity and predominant organism identity. Recent literature reveals previously undetected organisms and community characteristics that appear associated with certain urinary symptoms, including urinary tract infection and urgency urinary incontinence. The role of individual organisms may range from beneficial to pathogenic and may vary on the basis of an individual's FUM characteristics. The simple dichotomy of 'infected' or 'sterile' no longer sufficiently captures the microbiological complexity of the female bladder. SUMMARY: Deeper understanding of the FUM should yield better methods to restore the microbiota to a healthy state, providing symptom relief. Opportunities to modify the FUM without antibiotic use are exciting possibilities for future research; stand-alone antibiotic use may be reevaluated to improve treatment precision. Long-standing nomenclature for conditions such as asymptomatic bacteriuria and urinary tract infection will likely require modification. PMID- 27379440 TI - The Effects of Resveratrol Supplementation in Overweight and Obese Humans: A Systematic Review of Randomized Trials. AB - BACKGROUND: Obesity and metabolic syndrome are significant global health issues, with current public health messages predominately focused on altering dietary and physical activity behaviors. Resveratrol is a polyphenol (stilbenoid) commonly found in grapes, and human trials to date have shown conflicting and limited beneficial effects with respect to health. The aim of this study was to determine the effect of resveratrol supplementation on reducing body weight and modifying associated inflammatory markers. METHODS: A systematic review was undertaken following the PRISMA guidelines and using five indexed databases (OVID MEDLINE, Cochrane Library, Web of Science, SCOPUS, and CINAHL). A search strategy was formulated to select randomized, double-blind, placebo-controlled human trials investigating the effects of resveratrol supplementation on obesity or overweight, including body weight, metabolic and inflammatory markers. RESULTS: Five thousand five hundred sixty-nine studies published from 1990 to November 2015 were identified, with only nine papers meeting the inclusion criteria. The studies involved 208 participants (aged 49.2 +/- 8.3 years) and utilized a substantial range of resveratrol doses (75-3000 mg/day). Study durations were a minimum of 2 weeks (14-90 days). Seven studies indicated no significant change in body mass index or body weight (P > 0.05), and three studies showed no improvements in fat mass, fat volume, or abdominal fat distribution (P > 0.05). Four studies included measurements of inflammatory markers, with three of these finding resveratrol supplementation to have a significant positive effect (P > 0.05). CONCLUSION: Based on the included studies, there is currently insufficient evidence to support the recommendation of resveratrol supplements in management of obesity. However, there were significant but not entirely consistent anti inflammatory effects after resveratrol supplementation in overweight and obese individuals. PMID- 27379441 TI - Diffusion-weighted imaging reflects variable cellularity and stromal density present in breast fibroadenomas. AB - OBJECTIVE: To determine the underlying histopathologic features influencing apparent diffusion coefficient (ADC) values of breast fibroadenomas. MATERIALS AND METHODS: Biopsy-proven fibroadenomas (n=26) initially identified as suspicious on breast magnetic resonance imaging (MRI) were retrospectively evaluated. Histopathologic assessments of lesion cellularity and stromal type were compared with ADC measures on diffusion-weighted MRI. RESULTS: Presence of epithelial hyperplasia (increased cellularity) and dense collagenous stroma were both significantly associated with lower lesion ADC values (P=.02 and .004, respectively). CONCLUSION: Variations in epithelial cellularity and stromal type influence breast lesion ADC values and may explain the wide range of ADC measures observed in benign fibroadenomas. PMID- 27379442 TI - The Transmembrane Domain of a Bicomponent ABC Transporter Exhibits Channel Forming Activity. AB - Pseudomonas aeruginosa is an opportunistic pathogen that expresses two unique forms of lipopolysaccharides (LPSs) on its bacterial surface, the A- and B-bands. The A-band polysaccharides (A-band PSs) are thought to be exported into the periplasm via a bicomponent ATP-binding cassette (ABC) transporter located within the inner membrane. This ABC protein complex consists of the transmembrane (TMD) Wzm and nucleotide-binding (NBD) Wzt domain proteins. Here, we were able to probe ~1.36 nS-average conductance openings of the Wzm-based protein complex when reconstituted into a lipid membrane buffered by a 200 mM KCl solution, demonstrating the large-conductance, channel-forming ability of the TMDs. In agreement with this finding, transmission electron microscopy (TEM) imaging revealed the ring-shaped structure of the transmembrane Wzm protein complex. As hypothesized, using liposomes, we demonstrated that Wzm interacts with Wzt. Further, the Wzt polypeptide indeed hydrolyzed ATP but exhibited a ~75% reduction in the ATPase activity when its Walker A domain was deleted. The distribution and average unitary conductance of the TMD Wzm protein complex were altered by the presence of the NBD Wzt protein, confirming the regulatory role of the latter polypeptide. To our knowledge, the large-conductance, channel-like activity of the Wzm protein complex, although often hypothesized, has not previously been demonstrated. These results constitute a platform for future structural, biophysical, and functional explorations of this bicomponent ABC transporter. PMID- 27379443 TI - Word Gap Redux: Developmental Sequence and Quality. PMID- 27379444 TI - Alcohol-approach inclinations and drinking identity as predictors of behavioral economic demand for alcohol. AB - Behavioral economic demand curve indices of alcohol consumption reflect decisions to consume alcohol at varying costs. Although these indices predict alcohol related problems beyond established predictors, little is known about the determinants of elevated demand. Two cognitive constructs that may underlie alcohol demand are alcohol-approach inclinations and drinking identity. The aim of this study was to evaluate implicit and explicit measures of these constructs as predictors of alcohol demand curve indices. College student drinkers (N = 223, 59% female) completed implicit and explicit measures of drinking identity and alcohol-approach inclinations at 3 time points separated by 3-month intervals, and completed the Alcohol Purchase Task to assess demand at Time 3. Given no change in our alcohol-approach inclinations and drinking identity measures over time, random intercept-only models were used to predict 2 demand indices: Amplitude, which represents maximum hypothetical alcohol consumption and expenditures, and Persistence, which represents sensitivity to increasing prices. When modeled separately, implicit and explicit measures of drinking identity and alcohol-approach inclinations positively predicted demand indices. When implicit and explicit measures were included in the same model, both measures of drinking identity predicted Amplitude, but only explicit drinking identity predicted Persistence. In contrast, explicit measures of alcohol-approach inclinations, but not implicit measures, predicted both demand indices. Therefore, there was more support for explicit, versus implicit, measures as unique predictors of alcohol demand. Overall, drinking identity and alcohol-approach inclinations both exhibit positive associations with alcohol demand and represent potentially modifiable cognitive constructs that may underlie elevated demand in college student drinkers. (PsycINFO Database Record PMID- 27379445 TI - Incidence and Predictors of Nonalcoholic Fatty Liver Disease by Serum Biomarkers in Patients with Inflammatory Bowel Disease. AB - BACKGROUND: Patients with inflammatory bowel disease (IBD) are at high risk for non-alcoholic fatty liver disease (NAFLD). Longitudinal data on incident NAFLD are lacking. We employed non-invasive methods to study incidence and predictors of NAFLD. METHODS: This was a retrospective study of IBD patients without known liver disease followed at IBD clinic of McGill University. NAFLD was defined as Hepatic Steatosis Index (HSI) >=36 and absence of alcohol intake. Advanced liver fibrosis was diagnosed by FIB-4 >=2.67. Active IBD was defined as partial Mayo score >=3 for ulcerative colitis, Harvey Bradshaw Index >= 5 or flare during follow-up. Kaplan-Meier and Cox regression analyses were used to investigate incidence and predictors of NAFLD development. RESULTS: Three hundred twenty-one consecutive patients (median age 33.7 yr, 47% males) were observed for a median of 3.2 years (interquartile range 1.5-6). Over 1181.2 persons-year (PY), 108 (33.6%) patients developed NAFLD, accounting for an incidence rate of 9.1/100 PY (95% confidence interval [CI], 7.4-10.9). 7 (2.2%) patients developed advanced liver fibrosis, accounting for an incidence rate of 0.5/100 PY (95% CI, 0.2-1.1). Development of NAFLD was predicted by disease activity (adjusted hazard ratio [aHR] = 1.58; 95% CI, 1.08-2.33, P = 0.02), disease duration (aHR = 1.12; 95% CI, 1.03-1.23, P = 0.01), and prior surgery for IBD (aHR = 1.34; 95% CI, 1.04-1.74, P = 0.02). CONCLUSIONS: NAFLD is a frequent comorbidity in patients with IBD. These patients can also develop advanced liver fibrosis. Disease activity, duration of IBD and prior surgery are predictors of NAFLD development. This should represent one more incentive to achieve and maintain early clinical remission. Further prospective studies are of interest. PMID- 27379446 TI - Racial and Ethnic Minorities with Inflammatory Bowel Disease in the United States: A Systematic Review of Disease Characteristics and Differences. AB - BACKGROUND: Inflammatory bowel disease (IBD) has predominantly affected whites, particularly Ashkenazi Jews. Over the last 2 decades, IBD has "emerged" in minorities. Differences in natural history and disease characteristics have been suggested. The objective of this systematic review is to summarize these differences in studies from the United States. METHODS: A structured search was performed within the Medline database through PubMed, EMBASE, and Cochrane databases. Published studies of genetics, pathogenesis, prevalence or incidence, disease location and behavior, extraintestinal manifestations, disparities and access to care in patients with IBD who are of African American, Asian, and Hispanic descent living in the United States were eligible. RESULTS: A total of 47 studies were included for African Americans (n = 20,054), Hispanics (n = 10,762), and Asians (n = 2668). The incidence and prevalence of IBD is increasing among minorities. There is less of a genetic influence in the pathogenesis of IBD among African Americans; however, novel variants have been identified. There is a predilection for pancolonic ulcerative colitis among Hispanics and Asians. Crohn's disease-related hospitalizations are increasing in Asians, whereas African Americans are more likely to use the emergency department. No major differences are seen in disease location and behavior, upper gastrointestinal tract, and perianal involvement and extraintestinal manifestations among races and ethnic groups. Medication utilization seems to be similar. Differences in surgery are likely explained by health insurance status. CONCLUSIONS: Future prospective studies are needed to fully characterize disease characteristics and treatment response among minorities. With novel IBD therapies in the pipeline, enrollment in clinical trials should emphasize increased representation of all races and ethnic groups. PMID- 27379447 TI - Electrochemical Behavior of meso-Substituted Porphyrins: The Role of Cation Radicals to the Half-Wave Oxidation Potential Splitting. AB - In this study, the electrochemical behavior of free base and zinc meso substituted porphyrins is examined by cyclic voltammetry (CV) and density functional theory (DFT). The results show that the half-wave oxidation potential splitting of the two oxidation states (DeltaE= second E1/2 - first E1/2) of tetraphenylporphyrin (H2TPP) and its zinc complex (ZnTPP) are higher than those of porphyrins and their zinc complexes with meso-substituted five-membered heterocylic rings. The DeltaE values follow the trend of TPP > T(3'-thienyl)P > T(3'-furyl)P > T(2'-thienyl)P for both meso-porphyrins and their respective zinc complexes. By employing DFT calculations, we have found that the trend of DeltaE values is consistent with that of highest spin density (HSD) distribution and HOMO-LUMO energy gaps of cationic radicals as well as the pi-conjugation between central porphyrin and meso-substituted rings. Also, they exhibit the better resonance between the porphyrin ring with meso-substituted rings as moving from porphyrins and their zinc complexes with phenyl rings to five-membered heterocyclic rings. A good agreement between calculated and experimental results indicates that cationic radicals, especially their spin density distribution, do play an important role in half-wave oxidation potential splitting of meso porphyrins and their zinc complexes. PMID- 27379449 TI - The evolving frontier of diabetes therapy: The renaissance of glycemology. AB - It was previously proposed that diabetes could be a "cardiovascular disease". This concept was based on evidence showing that controlling hypertension and dyslipidemia could be more effective than controlling hyperglycemia. At that time it was concluded that the real need to focus on reaching optimal glycemic control had lost its appeal. However, the concept of glycemic control was strictly correlated to levels of glycated hemoglobin (HbA1c), the integrated measure of mean glycemia over the previous 2-3months, while recent evidence suggests that the concept of hyperglycemia has profoundly changed, and it is more appropriate to speak of different kinds or aspects of hyperglycemia. A modern, updated approach to glycemic control in people with diabetes, in fact, must focus not only on reaching and maintaining optimal HbA1c levels as soon as possible, but to obtain this result by reducing postprandial hyperglycemia and glycemic variability, while avoiding hypoglycemia. PMID- 27379448 TI - Simplified ultrasound protocol for the exclusion of clinically significant carotid artery stenosis. AB - OBJECTIVES: To evaluate a simplified ultrasound protocol for the exclusion of clinically significant carotid artery stenosis for screening purposes. MATERIAL AND METHODS: A total of 9,493 carotid arteries in 4,748 persons underwent carotid ultrasound examination. Most subjects were 65-year-old men attending screening for abdominal aortic aneurysm. The presence of a stenosis on B-mode and/or a mosaic pattern in post-stenotic areas on colour Doppler and maximum peak systolic velocity (PSV) in the internal carotid artery (ICA) were recorded. A carotid stenosis was defined as The North American Symptomatic Carotid Endarterectomy Trial (NASCET) >20% and a significant stenosis as NASCET >50%. The kappa (kappa) statistic was used to assess agreement between methods. Sensitivity, specificity, positive predictive (PPV), and negative predictive (NPV) values were calculated for the greyscale/mosaic method compared to conventional assessment by means of PSV measurement. RESULTS: An ICA stenosis was found in 121 (1.3%) arteries; 82 (0.9%) were graded 20%-49%, 16 (0.2%) were 50%-69%, and 23 (0.2%) were 70%-99%. Eighteen (0.2%) arteries were occluded. Overall, the greyscale/mosaic protocol showed a moderate agreement with ICA PSV measurements for the detection of carotid artery stenosis, kappa = 0.455. The sensitivity, specificity, PPV, and NPV for detection of >20% ICA stenosis were 91% (95% CI 0.84-0.95), 97% (0.97 0.98), 31% (0.26-0.36), and 97% (0.97-0.97), respectively. The corresponding figures for >50% stenosis were 90% (0.83-0.95), 97% (0.97-0.98), 11% (0.08-0.15), and 100% (0.99-1.00). CONCLUSION: Compared with PSV measurements, the simplified greyscale/mosaic protocol had a high negative predictive value for detection of >50% carotid stenosis, suggesting that it may be suitable as a screening method to exclude significant disease. PMID- 27379451 TI - Refractive Outcomes of Combined Cataract and Glaucoma Surgery. PMID- 27379450 TI - Clinical Characteristics of Patients With Double-Seronegative Myasthenia Gravis and Antibodies to Cortactin. AB - IMPORTANCE: Double-seronegative myasthenia gravis (dSNMG) includes patients with myasthenia gravis (MG) without detectable antibodies to the nicotinic acetylcholine receptor (AChR) or to muscle-specific tyrosine kinase (MuSK). The lack of a biomarker hinders the diagnosis and clinical management in these patients. Cortactin, a protein acting downstream from agrin/low-density lipoprotein receptor-related protein 4 (LRP4)/MuSK, has been described as an antigen in dSNMG. OBJECTIVE: To describe the frequency and clinical features of patients with dSNMG who have cortactin antibodies. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cross-sectional study was conducted at Hospital de la Santa Creu i Sant Pau, an institutional practice referral center in Barcelona, Spain, between May 1, 2015, and November 30, 2015. We included 250 patients with a definitive diagnosis of MG with available serum samples at the time of diagnosis. Descriptive and comparative data analyses were performed. EXPOSURES: Cortactin antibodies were measured by enzyme-linked immunosorbent assay and Western blot; AChR, MuSK, and anti-striated muscle antibodies were detected using a standard method; and LRP4 antibodies were tested using a cell-based assay. MAIN OUTCOMES AND MEASURES: The primary outcome was the frequency of patients with dSNMG who have cortactin antibodies. Secondary outcomes were demographic, clinical, neurophysiological, and laboratory data. RESULTS: Of 250 patients (mean [SD] age at onset, 49.7 [21.2] years; 56% female), 38 (15.2%) had dSNMG, 201 (80.4%) had MG with AChR antibodies, and 11 (4.4%) had MG with MuSK antibodies. Cortactin antibodies were identified in 28 patients with MG: 9 of 38 (23.7%) who had dSNMG, 19 of 201 (9.5%) who had MG with AChR antibodies (significantly lower than those with dSNMG: 9.5% vs 23.7%; P = .02), and 0 of 11 who had MG with MuSK antibodies; 0 of 29 controls had cortactin antibodies. At onset, among the 9 patients with dSNMG and cortactin antibodies, 6 had ocular MG and 3 had Myasthenia Gravis Foundation of America clinical classification IIA. Two patients with ocular MG developed generalized MG. The group with dSNMG and cortactin antibodies, compared with those who had MG with AChR antibodies, more frequently had mild forms at onset (100.0% vs 62.7%; P = .03), had fewer bulbar signs at maximal worsening (0% vs 41.3%; P = .01), and were younger at onset (median [interquartile range], 34.9 [9.5] vs 53.9 [38.5] years; P = .03); the group with dSNMG and cortactin antibodies also more frequently had ocular MG at onset than those with MG and AChR antibodies, although the difference was not statistically significant (66.7% vs 40.8%; P = .17). Of 17 patients with ocular dSNMG, 4 (23.5%) had antibodies to cortactin. CONCLUSIONS AND RELEVANCE: In this study, patients with cortactin antibodies and dSNMG had an ocular or mild generalized phenotype of MG. Including the detection of cortactin antibodies in the routine diagnosis of dSNMG may be helpful in ocular MG. PMID- 27379453 TI - Effects of Swimming Goggles Wearing on Intraocular Pressure, Ocular Perfusion Pressure, and Ocular Pulse Amplitude. AB - PURPOSE: To evaluate changes in the ocular pulse amplitude (OPA) and ocular perfusion pressure (OPP), and investigate factors associated with intraocular pressure (IOP) elevation due to periorbital compression during swimming goggles (SG) use. METHODS: This cross-sectional study evaluated 35 eyes of 35 healthy volunteers during the wearing of a drilled SG. OPP calculation, Goldman applanation tonometry, and OPA measurements (using Pascal dynamic contour tonometer) were performed before, during, and after SG use. Scleral rigidity (calculated with Schiotz tonometry readings), orbital rim area, exophthalmometry, spherical equivalent, axial length, corneal thickness, and the goggles' rubber elastic force were considered in the multivariable analysis as potentially related to IOP changes. RESULTS: SG significantly increased IOP after 2 minutes of use (13.34+/-2.67 vs. 23.46+/-7.20 mm Hg, P<0.0001). After removal, IOP decreased significantly (10.20+/-5.85 mm Hg, P<0.0001). A inverse correlation between IOP and OPP differences was observed with the SG wearing (r=-0.57; P=0.0003). Mean OPA was significantly higher during compared with before SG wear (2.57+/-1.34 vs. 1.82+/-0.55 mm Hg for the timepoints 2 and 1, respectively; P=0.0064). Only orbital rim area (P=0.0052) and elastic force (P=0.0019) were significantly associated with IOP elevation. CONCLUSIONS: SG provoked acute IOP elevation and disturbance in the ocular hemodynamics, which was associated with larger orbital rim area and greater SG elastic force. These findings could have implications for subjects at high risk for glaucoma onset or progression. PMID- 27379454 TI - Assessing Health Practitioner Knowledge of Appropriate Psychotropic Medication Use in Nursing Homes: Validation of the Older Age Psychotropic Quiz. AB - HOW TO OBTAIN CONTACT HOURS BY READING THIS ARTICLE INSTRUCTIONS XX contact hours will be awarded by Villanova University College of Nursing upon successful completion of this activity. A contact hour is a unit of measurement that denotes 60 minutes of an organized learning activity. This is a learner-based activity. Villanova University College of Nursing does not require submission of your answers to the quiz. A contact hour certificate will be awarded once you register, pay the registration fee, and complete the evaluation form online at http://goo.gl/gMfXaf. To obtain contact hours you must: 1. Read the article, "Assessing Health Practitioner Knowledge of Appropriate Psychotropic Medication Use in Nursing Homes: Validation of the Older Age Psychotropic Quiz" found on pages XX-XX, carefully noting any tables and other illustrative materials that are included to enhance your knowledge and understanding of the content. Be sure to keep track of the amount of time (number of minutes) you spend reading the article and completing the quiz. 2. Read and answer each question on the quiz. After completing all of the questions, compare your answers to those provided within this issue. If you have incorrect answers, return to the article for further study. 3. Go to the Villanova website listed above to register for contact hour credit. You will be asked to provide your name; contact information; and a VISA, MasterCard, or Discover card number for payment of the $20.00 fee. Once you complete the online evaluation, a certificate will be automatically generated. This activity is valid for continuing education credit until MONTH XX, 20XX. CONTACT HOURS This activity is co-provided by Villanova University College of Nursing and SLACK Incorporated. Villanova University College of Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. ACTIVITY OBJECTIVES 1. XXX 2. XXX DISCLOSURE STATEMENT Neither the planners nor the authors have any conflicts of interest to disclose. Despite widespread concern over psychotropic medication use, their regular administration continues in nursing homes. Consequently, it is vital that health practitioners in this setting have adequate knowledge of appropriate use. The Older Age Psychotropic Quiz (OAPQ) was developed to assess this knowledge, with psychometric testing reported herein. The 10-item OAPQ was constructed after substantial literature review and consultation with 10 experienced senior care professionals. Data from 36 nursing students, 461 nursing home staff, and 30 senior care pharmacists were used for validation analyses. Satisfactory construct validity was identified via the group comparison method (chi2 [2, n = 101] = 79.21, p < 0.001). Internal reliability was strong (alpha = 0.89). Test-retest reliability was acceptable over time (r = 0.77). Factor analysis resulted in a two-factor solution. Psychometric analyses support the OAPQ for use in the nursing home setting. [Journal of Gerontological Nursing, xx(x), xx-xx.]. PMID- 27379455 TI - Critical Association Between Mental Health Disorders and Medical Status: Depression Intervention Use Indicates a Two-Fold Risk for Subsequent Medical Events in Older American Home Health Care Patients. AB - The current study examined longitudinal associations between mental disorders and all-cause subsequent medical events in a 5% random sample of records in the 2010 national Outcome and Assessment Information Set. Records of older adults (N = 28,475) receiving home health care (HHC) services were examined with respect to mental disorders and medical events, including acute care hospitalization, emergency department admission, and 30-day rehospitalization. Predominant mental disorders were depression and anxiety identified by formal diagnoses, symptom clusters, and/or prescription of related mental health services. Depression intervention use was the strongest risk factor for all three types of medical events. However, 61.6% of patients receiving depression interventions did not screen positive at admission using the Patient Health Questionnaire-2. Moving forward, nurses must closely monitor high-risk older adults throughout the HHC stay using sensitive depression screening tools, as well as receive targeted training in geriatric psychiatry. [Journal of Gerontological Nursing, 42(10), 42 55.]. PMID- 27379456 TI - Prevalence of Erectile Dysfunction and Associated Factors in Korean Older Adults With Coronary Artery Disease. AB - The current study aimed to identify the prevalence and associated factors of erectile dysfunction (ED) among 161 Korean adults 60 and older with coronary artery disease (CAD). ED was diagnosed in 72.2% of patients-the prevalence of which was significantly associated with age, education, employment, monthly income, frequency of sexual intercourse, body mass index, and low-density lipoprotein. Health-related quality of life (HRQoL) was lower in patients with ED than in those without ED (p < 0.001). Hierarchical multiple regression analysis revealed that ED significantly influenced HRQoL in patients with CAD after adjusting for sociodemographic and disease-related characteristic variables (p < 0.001). Interventions and training courses for health care providers should focus on improving caregivers' knowledge and communication skills with patients and spouses regarding sexual health. Furthermore, guidelines to improve HRQoL in patients with CAD should consider incorporating sexual counseling. [Journal of Gerontological Nursing, 42(10), 32-41.]. PMID- 27379457 TI - Self-Assembly of Concentric Hexagons and Hierarchical Self-Assembly of Supramolecular Metal-Organic Nanoribbons at the Solid/Liquid Interface. AB - In an effort to exert more precise control over structural features of supramolecules, a series of giant concentric hexagons were assembled as discrete structures using tetratopic terpyridine (tpy) ligands. In preparation of tetratopic ligand, pyrylium and pyridinium salts chemistry significantly facilitated synthesis. The key compounds were obtained by condensation reactions of pyrylium salts with corresponding primary amine derivatives in good yields. These discrete metallo-supramolecular concentric hexagons were fully characterized by NMR, ESI-MS, TWIM-MS, and TEM, establishing their hexagon-in hexagon architectures. The combination of different tetratopic ligands also assembled hybrid concentric hexagons with increasing diversity and complexity. Furthermore, these concentric hexagon supramolecules with precisely controlled shapes and sizes were utilized as building blocks to hierarchically self-assemble supramolecular metal-organic nanoribbons (SMON) at solid-liquid interfaces. Ambient STM imaging showed the formation of long 1D SMON rather than 2D assembly on the basal plane of highly oriented pyrolytic graphite (HOPG) surface after simple dropcasting of the solution of preassembled concentric hexagons onto a freshly cleaved surface of HOPG. This wet chemical method based on self-assembly may offer simple, economical, and scalable routes to deliver complex materials. PMID- 27379458 TI - Risk estimation of second primary cancers after breast radiotherapy. AB - AIMS: There is evidence towards the induction of second primary cancers (SPCs) after breast radiotherapy (RT). Organs, such as the lungs and the esophagus, have been identified as common sites for SPC formation. As a result, the current study investigated the risk of secondary carcinogenesis associated with particular RT techniques for breast cancer; including whole breast, segmented breast, partial breast and mammosite brachytherapy. METHODS: In this study, seven breast cancer patients had all major organs contoured on their planning computed tomography (CT) images. Whole breast, segmented breast, accelerated partial breast irradiation (APBI) and mammosite boost treatment plans were generated for each patient using Pinnacle3 treatment planning system. Differential dose-volume histograms were generated for a number of critical structures: bladder, brain and central nervous system (CNS), breast, colon, liver, lung, mouth and pharynx, esophagus, ovary, salivary gland, small intestine, stomach, and uterus. The lifetime attributed risk (LAR) of cancer induction was estimated using the Schneider et al. excess absolute risk models and dose-volume histograms for the above organs. RESULTS: The sites with the highest LAR estimates were the ipsilateral and contralateral lungs, and contralateral breast for all treatment techniques. For all sites, the LAR estimates for the segmented breast and mammosite treatments were lower than those for the whole breast and APBI treatments. For right-sided target volumes the liver also resulted in high LAR estimates, with all techniques having a LAR greater than 20 per 10 000 person years (PY), except for mammosite with a mean LAR estimate of 13.2 per 10 000 PY. For left-sided target volumes the stomach also resulted in high LAR estimates, with both whole breast and APBI having a LAR greater than 20 per 10 000 PY, and mammosite the lowest with a LAR of 8.3 per 10 000 PY. CONCLUSION: It is concluded that the lungs and contralateral breast showed high LAR estimates. PMID- 27379459 TI - Alkylidene Dihydropyridines As Synthetic Intermediates: Model Studies toward the Synthesis of the Bis(piperidine) Alkaloid Xestoproxamine C. AB - Results of model studies demonstrating a stereoselective synthetic route to tricyclic analogues of the bis(piperidine) alkaloid xestoproxamine C are presented. Dearomatization of a tricyclic pyridine derivative to afford an alkylidene dihydropyridine (anhydrobase) intermediate followed by catalytic heterogeneous hydrogenation was used to install the correct relative stereochemistry about the bis(piperidine) ring system. Other key features of these model studies include development of an efficient ring-closing metathesis procedure to prepare macrocyclic derivatives of 3,4-disusbstituted pyridines, intramolecular cyclizations of alkylidene dihydropyridines to establish pyridine substituted pyrrolidines and piperidines, successful homologation of pyridine-4 carboxaldehydes using formaldehyde dimethyl thioacetal monoxide (FAMSO), and application of B-alkyl Suzuki coupling to assemble substituted pyridines. PMID- 27379460 TI - Visuospatial and verbal memory in mental arithmetic. AB - Working memory allows complex information to be remembered and manipulated over short periods of time. Correlations between working memory and mathematics achievement have been shown across the lifespan. However, only a few studies have examined the potentially distinct contributions of domain-specific visuospatial and verbal working memory resources in mental arithmetic computation. Here we aimed to fill this gap in a series of six experiments pairing addition and subtraction tasks with verbal and visuospatial working memory and interference tasks. In general, we found higher levels of interference between mental arithmetic and visuospatial working memory tasks than between mental arithmetic and verbal working memory tasks. Additionally, we found that interference that matched the working memory domain of the task (e.g., verbal task with verbal interference) lowered working memory performance more than mismatched interference (verbal task with visuospatial interference). Findings suggest that mental arithmetic relies on domain-specific working memory resources. PMID- 27379461 TI - pH/Reductant Dual-Responsive Core-Cross-Linked Micelles via Facile in Situ ATRP for Tumor-Targeted Delivery of Anticancer Drug with Enhanced Anticancer Efficiency. AB - Anticancer drugs cause severe side effects on normal tissues and organs due to their nonspecific delivery. Thus, tumor-targeting delivery of anticancer drugs remains a serious challenge in chemotherapy. Here a facile strategy was established for the pH/reductant dual-responsive core-cross-linked (CCL) micelles for tumor-targeted delivery of anticancer drug, via in situ atom transfer radical polymerization (ATRP). In the in vitro controlled release experiments with doxorubicin (DOX) as a model drug, the premature drug leakage rate was only 13.4% in the physiological medium within 36 h, while the cumulative release rate in the stimulated tumor microenvironment reached 78.7%, demonstrating the excellent tumor microenvironment responsive controlled release behavior upon acidic medium with high GSH level. As a folate receptor (FR) mediated targeting drug delivery system (DDS), the micelles showed excellent cytocompatibility, and enhanced anticancer efficiency after loading of DOX, compared with free DOX. PMID- 27379462 TI - Inherent Tracers for Carbon Capture and Storage in Sedimentary Formations: Composition and Applications. AB - Inherent tracers-the "natural" isotopic and trace gas composition of captured CO2 streams-are potentially powerful tracers for use in CCS technology. This review outlines for the first time the expected carbon isotope and noble gas compositions of captured CO2 streams from a range of feedstocks, CO2-generating processes, and carbon capture techniques. The C-isotope composition of captured CO2 will be most strongly controlled by the feedstock, but significant isotope fractionation is possible during capture; noble gas concentrations will be controlled by the capture technique employed. Comparison with likely baseline data suggests that CO2 generated from fossil fuel feedstocks will often have delta(13)C distinguishable from storage reservoir CO2. Noble gases in amine captured CO2 streams are likely to be low concentration, with isotopic ratios dependent on the feedstock, but CO2 captured from oxyfuel plants may be strongly enriched in Kr and Xe which are potentially valuable subsurface tracers. CO2 streams derived from fossil fuels will have noble gas isotope ratios reflecting a radiogenic component that will be difficult to distinguish in the storage reservoir, but inheritance of radiogenic components will provide an easily recognizable signature in the case of any unplanned migration into shallow aquifers or to the surface. PMID- 27379463 TI - Thermodynamics and Kinetics of Gas Storage in Porous Liquids. AB - The recent synthesis of organic molecular liquids with permanent porosity opens up exciting new avenues for gas capture, storage, and separation. Using molecular simulations, we study the thermodynamics and kinetics for the storage of CH4, CO2, and N2 molecules in porous liquids consisting of crown-ether-substituted cage molecules in a 15-crown-5 solvent. It is found that the intrinsic gas storage capacity per cage molecule follows the order CH4 > CO2 > N2, which does not correlate simply with the size of gas molecules. Different gas molecules are stored inside the cage differently; e.g., CO2 molecules prefer the cage's core whereas CH4 molecules favor both the core and the branch regions. All gas molecules considered can enter the cage essentially without energy barriers and leave the cage on a nanosecond time scale by overcoming a modest energy penalty. The molecular mechanisms of these observations are clarified. PMID- 27379464 TI - Experiences of hearing loss and views towards interventions to promote uptake of rehabilitation support among UK adults. AB - OBJECTIVE: Effective hearing loss rehabilitation support options are available. Yet, people often experience delays in receiving rehabilitation support. This study aimed to document support-seeking experiences among a sample of UK adults with hearing loss, and views towards potential strategies to increase rehabilitation support uptake. People with hearing loss were interviewed about their experiences of seeking support, and responses to hypothetical intervention strategies, including public awareness campaigns, a training programme for health professionals, and a national hearing screening programme. DESIGN: Semi structured qualitative interview design with thematic analysis. STUDY SAMPLE: Twenty-two people with hearing loss, aged 66-88. RESULTS: Three themes, representing barriers to receiving rehabilitation support and potential areas for intervention, were identified: making the journey from realization to readiness, combatting social stigma, and accessing appropriate services. Barriers to receiving support mostly focused on appraisal of hearing loss symptoms. Interventions enabling symptom appraisal, such as routine screening, or demonstrating how to raise the topic effectively with a loved one, were welcomed. CONCLUSIONS: Interventions to facilitate realization of hearing loss should be prioritized. Raising awareness of the symptoms and prevalence of hearing loss may help people to identify hearing problems and reduce stigma, in turn increasing hearing loss acceptance. PMID- 27379465 TI - Generalizability of Pharmacologic and Psychotherapy Clinical Trial Results for Posttraumatic Stress Disorder to Community Samples. AB - OBJECTIVE: The present study sought to quantify the generalizability of pharmacologic and psychotherapy clinical trial results in individuals with a DSM IV diagnosis of posttraumatic stress disorder (PTSD) to a large representative community sample. METHODS: Data were derived from the 2004-2005 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a large nationally representative sample of the adult US population. We applied a standard set of exclusion criteria representative of pharmacologic and psychotherapy clinical trials to all adults with a DSM-IV diagnosis of PTSD in the previous 12 months (n = 1,715) and then to a subsample of participants seeking treatment (n = 366). Our aim was to assess how many participants with PTSD would fulfill typical eligibility criteria. RESULTS: We found that more than 6 of 10 respondents from the overall PTSD sample and more than 7 of 10 respondents seeking treatment for PTSD would have been excluded by 1 exclusion criterion or more in a typical pharmacologic trial. In contrast, about 2 of 10 participants in the full sample and about 3 of 10 participants seeking treatment for PTSD would have been excluded in a typical psychotherapy efficacy trial. CONCLUSIONS: We found that psychotherapy trial results may be applied to most patients with PTSD in routine clinical practice. The designers of pharmacologic clinical trials should carefully consider the trade-offs between the application of each exclusion criterion and its impact on representativeness. Specification a priori of the goals of the study, better justification for each exclusion criterion, and estimation of the proportion of individuals ineligible for the trial would assist study design. Developing integrated forms of pharmacotherapy and psychotherapy that simultaneously target commonly overlapping psychiatric disorders may yield more informative results for mental health care providers and research funding agencies. PMID- 27379466 TI - The effect of parental 5,10-methylenetetrahydrofolate reductase 677C/T and 1298A/C gene polymorphisms on response to single-dose methotrexate in tubal ectopic pregnancy. AB - OBJECT: The aim of this study was to assess the effect of parental 5,10 methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (677C/T and 1298A/C) on response to single-dose methotrexate (MTX) treatment in tubal ectopic pregnancy (TEP). MATERIALS AND METHODS: In this prospective cohort study, cases with unruptured TEPs were grouped into two according to their response to single dose MTX treatment (Group 1: responsive, n:88; Group 2: unresponsive, n:21). The groups were compared with regard to baseline demographic and clinical parameters. As a main outcome measure, the independent effects of parental MTHFR gene polymorphisms on response to single dose MTX treatment were evaluated. RESULTS: One hundred and nine unruptured TEP were included in the final analysis. The mean maternal age was 29.30 +/- 5.21 years, gravity 2 (min-max: 1-5), parity 1 (min max: 0-4). The median serum beta-human chorionic gonadotropin (beta-hCG) was 1403.35 MI/I (Q1-Q3: 517-2564). The overall response rate was 81% (88/109). The groups were similar with respect to basic baseline demographic data and serum beta-hCG level. Binary logistic regression analysis showed that the presence of parental MTHFR677C/T and 1298A/C polymorphism were not independent factor predicting treatment success (p > 0.05). The only independent factor for resistance to single dose MTX was the previous TEP (OR: 4.47 (1.18-16.9)). CONCLUSION: Parental MTHFR 677C/T and 1298A/C mutations do not predict the outcome of single dose intramuscular MTX treatment in unruptured TEP. PMID- 27379467 TI - Hypertension, lipoprotein subclasses and lipid transfer proteins in obese children and adolescents. AB - BACKGROUND: Obesity-related childhood hypertension is associated with disturbances of serum lipids, but less is known about distribution of lipoprotein subclasses and activities of proteins involved in reverse cholesterol transport in hypertensive obese children. Our objective was to determine low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses distribution and activities of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in hypertensive and non-hypertensive obese children. METHODS: A total of 40 hypertensive and 25 non-hypertensive obese children were enrolled. Lipoprotein subclasses were assessed by polyacrylamide gradient gel electrophoresis. LCAT and CETP activities were determined as a rate of formation and a rate of transfer of cholesteryl esters. RESULTS: Despite of comparable values of serum lipid parameters, a shift toward smaller LDL and HDL subclasses was observed in hypertensive compared to normotensive obese children. Activities of LCAT were similar, but proatherogenic CETP activities were significantly higher in the hypertensive group (p = 0.036). LCAT/net CETP ratio inversely correlated with relative proportion of small, dense LDL particles (rho = -0.423; p = 0.025) in the group with hypertension. CONCLUSIONS: The results of our study demonstrated a tendency toward altered distribution of lipoprotein subclasses in favor of more proatherogenic particles in childhood hypertension. Also, hypertensive obese children had increased proatherogenic CETP activity. PMID- 27379468 TI - An Efficient Variational Principle for the Direct Optimization of Excited States. AB - We present a variational principle that enables systematically improvable predictions for individual excited states through an efficient Monte Carlo evaluation. We demonstrate its compatibility with different ansatzes and with both real space and Fock space sampling and discuss its potential for use in the solid state. In numerical demonstrations for challenging molecular excitations, the method rivals or surpasses the accuracy of very high level methods using drastically more compact wave function approximations. PMID- 27379469 TI - Detection of Asymptomatic Choroiditis by Fundus Examination in Vogt-Koyanagi Harada Disease. AB - PURPOSE: To describe the ophthalmoscopic changes of the choroidal vessels in the posterior pole of Vogt-Koyanagi-Harada disease patients whose choroid is thickened due to asymptomatic choroiditis. METHODS: Three patients whose choroidal vessels are indistinct or not visible in the posterior pole by ophthalmoscopy were examined by fundus photography and enhanced-depth imaging optical coherence tomography (EDI-OCT). RESULTS: They did not complain of vision problems, and visual acuity was good. Serous retinal detachment was not observed by ophthalmoscopy or by OCT. However, choroidal thickening was observed in the EDI-OCT, while choroidal vessels became blurred or invisible on ophthalmoscopy. After steroid therapy, choroidal thickness decreased to normal levels and the small and large choroidal vessels previously indiscernible became visible by ophthalmoscopy and fundus photography. CONCLUSIONS: Asymptomatic choroiditis not accompanied by serous retinal detachment can be detected and assessed by observing the changes in the choroidal vessels by ophthalmoscopy and fundus photography. PMID- 27379470 TI - The Montpellier Leishmania Collection, from a Laboratory Collection to a Biological Resource Center: A 39-Year-Long Story. AB - We report the development of a laboratory collection of Leishmania that was initiated in 1975 and, after 39 years, has become an international Biological Resource Center (BRC-Leish, Montpellier, France, BioBank No. BB-0033-00052), which includes 6353 strains belonging to 36 Leishmania taxa. This is a retrospective analysis of the technical and organizational changes that have been adopted over time to take into account the technological advances and related modifications in the collection management and quality system. The technical improvements concerned the culture and cryopreservation techniques, strain identification by isoenzymatic and molecular techniques, data computerization and quality management to meet the changes in international standards, and in the cryogenic and microbiological safety procedures. The BRC is working toward obtaining the NF-S 96-900 certification in the coming years. Our long-term expertise in Leishmania storage and typing and collection maintenance should encourage field epidemiologists and clinical practitioners in endemic countries to secure their own strain collection with the help of the French BRC-Leish. PMID- 27379471 TI - Polyamines, myosin heavy chains, and collagen specific amino acids after a repeated bout of eccentric exercise. AB - We investigated alternatives to commonly used biomarkers of exercise-induced tissue damage. Over 5 days following two bouts of 100 drop-to-vertical jumps (inter-bout rest period of 3 weeks), myosin heavy chain 1, hydroxylysine (HYL), hydroxyproline (HYP), spermine (SPM) and spermine synthase (SMS) were measured in the serum of 10 participants. HYL significantly increased from 5.92 +/- 1.49 ng/mL to 6.48 +/- 1.47 ng/mL at 24 h. A similar trend was observed for bout 2, but without reaching significance. SPM significantly increased only after bout 1 from 0.96 +/- 0.19 ng/mL at pretest to a peak level of 1.12 +/- 0.26 ng/mL at 24 h, while B2 increments remained non-significant. Myosin heavy chain 1, HYP and SMS values remained below the detection limit of the applied enzyme-linked immunosorbent assay (ELISA) kit. Though HYL and SM increased after the intervention, both markers showed a large standard deviation (SD) combined with small increments. Therefore, none of the investigated biomarkers provides a meaningful alternative to commonly used damage markers. PMID- 27379472 TI - Single-Electron Transmetalation via Photoredox/Nickel Dual Catalysis: Unlocking a New Paradigm for sp(3)-sp(2) Cross-Coupling. AB - The important role of transition metal-catalyzed cross-coupling in expanding the frontiers of accessible chemical territory is unquestionable. Despite empowering chemists with Herculean capabilities in complex molecule construction, contemporary protocols are not without their Achilles' heel: Csp(3)-Csp(2)/sp(3) coupling. The underlying challenge in sp(3) cross-couplings is 2-fold: (i) methods employing conventional, bench-stable precursors are universally reliant on extreme reaction conditions because of the high activation barrier of transmetalation; (ii) circumvention of this barrier invariably relies on use of more reactive precursors, thereby sacrificing functional group tolerance, operational simplicity, and broad applicability. Despite the ubiquity of this problem, the nature of the transmetalation step has remained unchanged from the seminal reports of Negishi, Suzuki, Kumada, and Stille, thus suggesting that the challenges in Csp(3)-Csp(2)/sp(3) coupling result from inherent mechanistic constraints in the traditional cross-coupling paradigm. Rather than submitting to the limitations of this conventional approach, we envisioned that a process rooted in single-electron reactivity could furnish the same key metalated intermediate posited in two-electron transmetalation, while demonstrating entirely complementary reactivity patterns. Inspired by literature reports on the susceptibility of organoboron reagents toward photochemical, single-electron oxidative fragmentation, realization of a conceptually novel open shell transmetalation framework was achieved in the facile coupling of benzylic trifluoroborates with aryl halides via cooperative visible-light activated photoredox and Ni cross-coupling catalysis. Following this seminal study, we disclosed a suite of protocols for the cross-coupling of secondary alkyl, alpha alkoxy, alpha-amino, and alpha-trifluoromethylbenzyltrifluoroborates. Furthermore, the selective cross-coupling of Csp(3) organoboron moieties in the presence of Csp(2) organoboron motifs was also demonstrated, highlighting the nuances of this approach to transmetalation. Computational modeling of the reaction mechanism uncovered useful details about the intermediates and transition-state structures involved in the nickel catalytic cycle. Most notably, a unique dynamic kinetic resolution process, characterized by radical homolysis/recombination equilibrium of a Ni(III) intermediate, was discovered. This process was ultimately found to be responsible for stereoselectivity in an enantioselective variant of these cross-couplings. Prompted by the intrinsic limitations of organotrifluoroborates, we sought other radical feedstocks and quickly identified alkylbis(catecholato)silicates as viable radical precursors for Ni/photoredox dual catalysis. These hypervalent silicate species have several notable benefits, including more favorable redox potentials that allow extension to primary alkyl systems incorporating unprotected amines as well as compatibility with less expensive Ru-based photocatalysts. Additionally, these reagents exhibit an amenability to alkenyl halide cross-coupling while simultaneously expanding the aryl halide scope. In the process of exploring these reagents, we serendipitously discovered a method to effect thioetherification of aryl halides via a H atom transfer mechanism. This latter discovery emphasizes that this robust cross-coupling paradigm is "blind" to the origins of the radical, opening opportunities for a wealth of new discoveries. Taken together, our studies in the area of photoredox/nickel dual catalysis have validated single electron transmetalation as a powerful platform for enabling conventionally challenging Csp(3)-Csp(2) cross-couplings. More broadly, these findings represent the power of rational design in catalysis and the strategic use of mechanistic knowledge and manipulation for the development of new synthetic methods. PMID- 27379473 TI - Redox-Dependent Dynamics in Heme-Bound Bacterial Iron Response Regulator (Irr) Protein. AB - The iron response regulator (Irr) protein from Bradyrhizobium japonicum mediates iron-dependent regulation of heme biosynthesis. Irr degrades in response to heme availability through a process that involves the binding of heme to Cys-29 in the heme regulatory motif (HRM) in the presence of molecular oxygen. In this work, we assessed the dynamics of one-electron reduction of heme-bound Irr by monitoring the formation of transient intermediates by pulse radiolysis. Hydrated electrons generated by pulse radiolysis reduced heme iron-bound Irr, facilitating the binding of molecular oxygen to the heme iron in Irr through an initial intermediate with an absorption maximum at 420 nm. This initial intermediate was converted to a secondary intermediate with an absorption maximum at 425 nm, with a first-order rate constant of 1.0 * 10(4) s(-1). The Cys-29 -> Ala (C29A) mutant of Irr, on the other hand, did not undergo the secondary phase, implying that ligand exchange of Cys-29 for another ligand takes place during the process. Spectral changes during the reduction of the heme-bound Irr revealed that binding of CO to ferrous heme consisted of two phases with kon values of 1.3 * 10(5) and 2.5 * 10(4) M(-1) s(-1), a finding consistent with the presence of two distinct hemes in Irr. In aerobic solutions, by contrast, oxidation of the ferrous heme to the ferric form was found to be a two-phase process. The C29A mutant was similarly oxidized, but this occurred as a single-phase process. We speculate that a reactive oxygen species essential for degradation of the protein is generated during the oxidation process. PMID- 27379474 TI - Transitions in romantic relationships and development of self-esteem. AB - Research suggests that self-esteem increases during late adolescence and young adulthood, but that there is large interindividual variability in this development. However, little is known about the factors accounting for these findings. Using propensity score matching, we tested whether important transitions in the domain of romantic relationships (i.e., beginning a relationship, marrying, and breaking up) explain why individuals differ in the particular self-esteem trajectory they follow. Data came from a longitudinal German study with a large sample of 3 nationally representative cohorts of late adolescents and young adults (total N = 9,069). The analyses were based on 4 assessments across a 3-year period. Using matched samples, the results showed that beginning a relationship increased self-esteem and that the increase persisted when the relationship held at least for 1 year. Experiencing a relationship break-up decreased self-esteem, but the effect disappeared after 1 year, even if the participant stayed single. Marrying did not influence self esteem. Additionally, we tested for selection effects of self-esteem on the later occurrence of relationship transitions. High self-esteem predicted the beginning of a relationship and low self-esteem predicted relationship break-up. All findings held across gender, age, and migration background. Furthermore, relationship quality mediated the effect of self-esteem on relationship break-up and the effect of beginning a longer versus a short relationship on self-esteem. The findings have significant implications because they show that self-esteem influences whether important transitions occur in the relationship domain and that, in turn, experiencing these transitions influences the further development of self-esteem. (PsycINFO Database Record PMID- 27379475 TI - Low-Lying Electronic States of CuAu. AB - Coinage metal diatomic molecules are building blocks for nanostructured materials, electronic devices, and catalytically or photochemically active systems that are currently receiving lively interest in both fundamental and applied research. The theoretical study presented here elucidates the electronic structure in the ground and several low-lying excited states of the diatomic molecule CuAu that result from the combination of the atoms in their ground states nd(10)(n + 1)s(1 2)S and lowest excited d-hole states nd(9)(n + 1)s(2 2)D (n = 3 for Cu, n = 5 for Au). Full and smooth potential energy curves, obtained at the multireference configuration interaction (MRCI) level of theory, are presented for the complete set of the thus resulting 44 Lambda-S terms and 86 Omega terms. Our approach is based on a scalar relativistic description using the Douglas-Kroll-Hess (DKH) Hamiltonian, with subsequent perturbative inclusion of spin-orbit (SO) coupling via the spin-orbit terms of the Breit-Pauli (BP) Hamiltonian. The Omega terms span an energy interval of about 7 eV at the ground state's equilibrium distance. Spectroscopic constants, calculated for all terms, are shown to accurately reproduce the observation for those nine terms that are experimentally known. PMID- 27379479 TI - A Perspective on Hospice Reform and Additional Caregiver Support. PMID- 27379480 TI - A Perspective on Hospice Reform and Additional Caregiver Support-Reply. PMID- 27379481 TI - Osteoporosis Overtreatment-A Clinical Problem That Needs to Be Discussed. PMID- 27379482 TI - A Perspective on Hospice Reform and Additional Caregiver Support-Reply. PMID- 27379483 TI - Telemedicine in Heart Failure-Ineffective or Just Ill Used? PMID- 27379484 TI - Telemedicine in Heart Failure-Ineffective or Just Ill Used? PMID- 27379485 TI - Telemedicine in Heart Failure-Ineffective or Just Ill Used?-Reply. PMID- 27379487 TI - Error in SI Conversion Factor. PMID- 27379486 TI - The Two-Question Method in Other High-Stress Settings. PMID- 27379488 TI - Association of Higher Consumption of Foods Derived From Subsidized Commodities With Adverse Cardiometabolic Risk Among US Adults. AB - IMPORTANCE: Food subsidies are designed to enhance food availability, but whether they promote cardiometabolic health is unclear. OBJECTIVE: To investigate whether higher consumption of foods derived from subsidized food commodities is associated with adverse cardiometabolic risk among US adults. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis of the National Health and Nutrition Examination Survey data from 2001 to 2006. Our final analysis was performed in January 2016. Participants were 10 308 nonpregnant adults 18 to 64 years old in the general community. EXPOSURE: From a single day of 24-hour dietary recall in the National Health and Nutrition Examination Survey, we calculated an individual level subsidy score that estimated an individual's consumption of subsidized food commodities as a percentage of total caloric intake. MAIN OUTCOMES AND MEASURES: The main outcomes were body mass index (calculated as weight in kilograms divided by height in meters squared), abdominal adiposity, C-reactive protein level, blood pressure, non-high-density lipoprotein cholesterol level, and glycemia. RESULTS: Among 10 308 participants, the mean (SD) age was 40.2 (0.3) years, and a mean (SD) of 50.5% (0.5%) were male. Overall, 56.2% of calories consumed were from the major subsidized food commodities. United States adults in the highest quartile of the subsidy score (compared with the lowest) had increased probabilities of having a body mass index of at least 30 (prevalence ratio, 1.37; 95% CI, 1.23-1.52), a ratio of waist circumference to height of at least 0.60 (prevalence ratio, 1.41; 95% CI, 1.25-1.59), a C-reactive protein level of at least 0.32 mg/dL (prevalence ratio, 1.34; 95% CI, 1.19-1.51), an elevated non high-density lipoprotein cholesterol level (prevalence ratio, 1.14; 95% CI, 1.05 1.25), and dysglycemia (prevalence ratio, 1.21; 95% CI, 1.04-1.40). There was no statistically significant association between the subsidy score and blood pressure. CONCLUSIONS AND RELEVANCE: Among US adults, higher consumption of calories from subsidized food commodities was associated with a greater probability of some cardiometabolic risks. Better alignment of agricultural and nutritional policies may potentially improve population health. PMID- 27379489 TI - The 30 Million-Word Gap: Relevance for Pediatrics. PMID- 27379490 TI - Neuroscience-based Nomenclature (NbN): A call for action. PMID- 27379491 TI - Call for Papers for JAMA Pediatrics Contest for Trainees. PMID- 27379492 TI - Implementation of transdiagnostic cognitive therapy in community behavioral health: The Beck Community Initiative. AB - OBJECTIVE: Progress bringing evidence-based practice (EBP) to community behavioral health (CBH) has been slow. This study investigated feasibility, acceptability, and fidelity outcomes of a program to implement transdiagnostic cognitive therapy (CT) across diverse CBH settings, in response to a policy shift toward EBP. METHOD: Clinicians (n = 348) from 30 CBH programs participated in workshops and 6 months of consultation. Clinician retention was examined to assess feasibility, and clinician feedback and attitudes were evaluated to assess implementation acceptability. Experts rated clinicians' work samples at baseline, mid-, and end-of-consultation with the Cognitive Therapy Rating Scale (CTRS) to assess fidelity. RESULTS: Feasibility was demonstrated through high program retention (i.e., only 4.9% of clinicians withdrew). Turnover of clinicians who participated was low (13.5%) compared to typical CBH turnover rates, even during the high-demand training period. Clinicians reported high acceptability of EBP and CT, and self-reported comfort using CT improved significantly over time. Most clinicians (79.6%) reached established benchmarks of CT competency by the final assessment point. Mixed-effects hierarchical linear models indicated that CTRS scores increased significantly from baseline to the competency assessment (p < .001), on average by 18.65 points. Outcomes did not vary significantly between settings (i.e., outpatient vs. other). CONCLUSIONS: Even clinicians motivated by policy-change rather than self-nomination may feasibly be trained to deliver a case-conceptualization driven EBP with high levels of competency and acceptability. (PsycINFO Database Record PMID- 27379493 TI - Detection of Molecular Alterations in Medullary Thyroid Carcinoma Using Next Generation Sequencing: an Institutional Experience. AB - Medullary thyroid carcinoma (MTC) harbors rearranged during transfection (RET) gene and rarely RAS gene mutations. The knowledge of the type of gene mutation in MTC is important to determine the treatment of the patients and the management of their family members. Targeted next-generation sequencing with a panel of 47 genes was performed in a total of 12 cases of sporadic (9/12) and hereditary MTC (3/12). Two of three hereditary MTCs had RET/C634R mutation, while the other one harbored two RET mutations (L790F and S649L). All the sporadic MTC had RET/M918T mutation except one case with HRAS mutation. Next-generation sequencing (NGS) can provide comprehensive analysis of molecular alterations in MTC in a routine clinical setting, which facilitate the management of the patient and the family members. PMID- 27379494 TI - Arachnoid cyst: a further anomaly associated with Kallmann syndrome? AB - BACKGROUND: Kallmann syndrome (KS) is defined by the association of hypogonadotropic hypogonadism and anosmia. It is characterized by a significant clinical and genetic heterogeneity; actually, it may present several non reproductive non-olfactory anomalies, and all the ways of genetic transmission can be involved in the inheritance of the disease. Although six pathogenesis related genes have been identified so far, KS remains sporadic in 70 % of the cases, and the genetic diagnosis is not available for all of them. The purpose of this paper is to present a further disease that can enrich the wide spectrum of KS variability, that is cerebral arachnoid cyst. CASE DESCRIPTION: This 11-year old boy presented with the typical characteristics of KS together with those related to a sylvian arachnoid cyst. He was admitted because of worsening headache. At the admission, the physical examination revealed eunuchoid aspect, micropenis, previous cryptorchidism, and anosmia. MRI pointed out a large, left sylvian arachnoid cyst, agenesia of the olfactory bulbs/tracts complex, and hypoplasia of the left olfactory sulcus. The child was operated on by endoscopic fenestration of the cyst, followed by transient external drainage for subdural hygroma and microscopic fenestration for recurrence of the cyst. His statural growth is normal but the sexual development still delayed in spite of hormone replacement therapy. CONCLUSION: According to the present and the other four cases in the literature, arachnoid cyst should be included among the anomalies possibly accompanying KS date although this association seems to be occasional as far as embryogenesis and physiopathology are concerned. PMID- 27379497 TI - Sesquiterpenoids from the Rhizomes of Homalomena occulta. AB - Naturally occurring oplopanane sesquiterpenoids are rarely reported. A phytochemical investigation on the rhizomes of Homalomena occulta (Lours) has resulted in the discovery of six oplopanane sesquiterpenoids (1-6), including four new (1-4) and one 3,5-seco-oplopanane (6), together with three previously reported sesquiterpenoids (7-9). In addition three new oplopananes (2a-4a) were also obtained by chemical transformation. All structures of these sesquiterpenoids were established based on the comprehensive spectroscopic analyses, including NMR, MS, and IR, and comparing with the literatures. PMID- 27379496 TI - Impact of aspirin use on morbidity and mortality in massively transfused cardiac surgery patients: a propensity score matched cohort study. AB - PURPOSE: Aspirin may prevent organ dysfunction in critically ill patients and mitigate transfusion associated acute lung injury. We hypothesized that aspirin use might be associated with decreased morbidity and mortality in massively transfused cardiac surgery patients. METHODS: A single center retrospective cohort study was performed using data from an 8.5-year period (2006-2014). Massive transfusion was defined as receiving at least 2400 ml (8 units) of red blood cell units intraoperatively. A propensity score model was created to account for the likelihood of receiving aspirin and matched pairs were identified using global optimal matching. The primary endpoint, in-hospital mortality, was compared between aspirin users and non-users. Secondary outcomes including: ICU hours, mechanical lung ventilation hours, prolonged mechanical lung ventilation (>24 h), pneumonia, stroke, acute renal failure, atrial fibrillation, deep sternal wound infection, and multiple organ dysfunction syndrome were also compared. RESULTS: Of 7492 cardiac surgery patients, 452 (6 %) were massively transfused and mortality was 30.6 %. There were 346 patients included in the matched cohort. No significant association was found between preoperative aspirin use and in-hospital mortality; absolute risk reduction with aspirin = 7.5 % (95 % CI -2.0 to 16.9 %, p = 0.12). Preoperative aspirin use was associated with fewer total mechanical lung ventilation hours (p = 0.02) and less prolonged mechanical lung ventilation; absolute risk reduction = 11.0 % (95 % CI 1.1-20.5 %, p = 0.02). CONCLUSIONS: Preoperative aspirin use is not associated with decreased in hospital mortality in massively transfused cardiac surgery patients, but may be associated with less mechanical lung ventilation time. PMID- 27379495 TI - Pre-radiation chemotherapy improves survival in pediatric diffuse intrinsic pontine gliomas. AB - BACKGROUND: The median survival of patients with diffuse intrinsic pontine glioma (DIPG) remains less than 1 year. The BSG 98 pre-irradiation chemotherapy protocol showed a significant increase in overall survival. In contrast to current treatment strategies, patients did not have to undergo surgical stereotactic biopsy, which can sometimes lead to complications, to be included in this protocol. MATERIALS AND METHODS: We retrospectively reviewed all the cases of DIPG that were treated in our department from September 15, 2004 to September 15, 2014. We compared the group of patients who followed our BSG 98 protocol to those who were treated with new targeted therapy protocols where systematic biopsy was required. RESULTS: Patients in the BSG 98 protocol were treated with BCNU, cisplatin, and methotrexate, followed by radiation at disease progression. Targeted therapy protocols included radiation therapy along with treatment by erlotinib, cilengitide, or an association of nimotuzumab and vinblastine. Sixteen patients were treated with the BSG 98 protocol, and 9 patients were treated with new targeted therapy protocols. Median overall survival was significantly higher in the BSG 98 group compared to the targeted therapy group (16.1 months (95 % CI, 10.4-19.0) vs 8.8 months (95 % CI 1.4-12.3); p = 0.0003). An increase in the median progression-free survival was observed (respectively, 8.6 vs 3.0 months; p = 0.113). CONCLUSION: The present study confirms that the BSG 98 protocol is one of the most effective current treatment strategies for DIPG. It may be used as the control arm in randomized trials investigating the use of innovative treatments and may be proposed to families who are averse to biopsy. PMID- 27379498 TI - Lack of pharmacokinetic drug-drug interaction between ramucirumab and paclitaxel in a phase II study of patients with advanced malignant solid tumors. AB - PURPOSE: The objective of this phase II study was to evaluate pharmacokinetic interaction potential between ramucirumab and paclitaxel in patients with advanced cancer. METHODS: This study was designed to assess 2-way pharmacokinetic drug-drug interactions between ramucirumab and paclitaxel. Twenty-four patients participated in Part A, which consisted of a 2-week monotherapy period in which paclitaxel 80 mg/m(2) was administered on day 1, followed by a 4-week cycle of combination treatment with ramucirumab (8 mg/kg on days 1 and 15; paclitaxel on days 1, 8, and 15). Patients could continue to receive combination therapy with ramucirumab and paclitaxel. In 16 patients in Part B, ramucirumab monotherapy was administered on day 1 of a 3-week cycle. Patients could continue to receive ramucirumab monotherapy or combination therapy with paclitaxel. RESULTS: Concomitant administration of ramucirumab had no effect on pharmacokinetics of paclitaxel, with ratios of geometric least squares (LS) means (with ramucirumab vs. alone) of 1.09 (90 % confidence interval [CI] 0.93, 1.29) for AUC(0-infinity) and 0.97 (90 % CI 0.83, 1.13) for C max. In addition, similar ramucirumab pharmacokinetic characteristics were observed with or without paclitaxel administration. The ratios of geometric LS means of AUC(0-infinity) and C max of ramucirumab (with paclitaxel vs. alone) were 1.00 (90 % CI 0.84, 1.19) for AUC(0 infinity) and 1.07 (90 % CI 0.93, 1.24) for C max, respectively. CONCLUSIONS: Concomitant paclitaxel administration is unlikely to affect the pharmacokinetics of ramucirumab, and vice versa. The incidence and severity of adverse events were consistent with the known safety profiles of paclitaxel and ramucirumab. PMID- 27379499 TI - Correlation between ADAMTS13 activity and neurological impairment in acute thrombotic microangiopathy patients. AB - Differential diagnosis between thrombotic thrombocytopenic purpura (TTP) and other thrombotic microangiopathies (TMA) is usually difficult because of frequently overlapping clinical presentations. Severely depressed ADAMTS13 activity (<10 %) seems distinctive for TTP because of its pathogenetic role. However a long debate exists in the literature about its sensibility and specificity. Our aim was to search for clinical differences between TMA patients referred to our laboratory, comparing them for protease activity <10 versus >=10 %. ADAMTS13 activity >=10 % patients (n = 73) showed a higher prevalence of drug- (p = 0.005) and cancer-associated (p < 0.001) TMA. Mean platelet count and renal dysfunction prevalence was lower (p < 0.001), while neurological impairment was more frequent (p = 0.001) in the <10 % ADAMTS13 activity group (n = 109), confirming previous literature findings. When taken neurological manifestations singularly, epilepsy (p = 0.04), focal motor deficit (p < 0.001) and cranial nerve palsy (p = 0.007) were more frequent in the <10 % activity group. In our case series, a <10 % ADAMTS13 activity depicts a group of patients with clinical features similar to TTP patients. Focal motor impairment or epileptic manifestations could further address toward a TTP diagnosis. Studies about treatment efficacy and follow-up are advised to determine whether laboratory findings can guide therapeutic decisions. PMID- 27379500 TI - Dysautonomic polyneuropathy as a variant of chronic inflammatory "demyelinating" polyneuropathy? AB - This report describes the clinical course over almost one decade of a male patient presenting with immune-mediated pure autonomic neuropathy resembling a distinct variant of chronic dysimmune polyneuropathies. We suppose autoantibodies directed against epitopes on autonomic axons or neurons causative for the symptoms. PMID- 27379501 TI - A pose prediction approach based on ligand 3D shape similarity. AB - Molecular docking predicts the best pose of a ligand in the target protein binding site by sampling and scoring numerous conformations and orientations of the ligand. Failures in pose prediction are often due to either insufficient sampling or scoring function errors. To improve the accuracy of pose prediction by tackling the sampling problem, we have developed a method of pose prediction using shape similarity. It first places a ligand conformation of the highest 3D shape similarity with known crystal structure ligands into protein binding site and then refines the pose by repacking the side-chains and performing energy minimization with a Monte Carlo algorithm. We have assessed our method utilizing CSARdock 2012 and 2014 benchmark exercise datasets consisting of co-crystal structures from eight proteins. Our results revealed that ligand 3D shape similarity could substitute conformational and orientational sampling if at least one suitable co-crystal structure is available. Our method identified poses within 2 A RMSD as the top-ranking pose for 85.7 % of the test cases. The median RMSD for our pose prediction method was found to be 0.81 A and was better than methods performing extensive conformational and orientational sampling within target protein binding sites. Furthermore, our method was better than similar methods utilizing ligand 3D shape similarity for pose prediction. PMID- 27379502 TI - Reduction of misregistration on cerebral four-dimensional computed tomography angiography images using advanced patient motion correction reconstruction. AB - PURPOSE: The aim of this study was to evaluate whether advanced patient motion correction (APMC) can reduce the misregistration of pixels between the different X-ray tube positions in four-dimensional CT angiography (4D-CTA). MATERIALS AND METHODS: Eight patients with intracranial aneurysms were included in this retrospective study. We compared the CTA images with APMC reconstruction and half scan reconstruction with regard to the following 3 items: (1) bone misalignment area; (2) image noise; and (3) aneurysm volume change. RESULTS: The bone misalignment area and image noise were significantly reduced in the APMC images, as compared to that in the half-scan reconstruction images (bone misalignment area: 33.0 +/- 18.1 cm(3) vs 152.0 +/- 72.2 cm(3), respectively; p < 0.001) (image noise at pons: 9.70 +/- 2.58 vs 15.16 +/- 5.02, respectively, p < 0.001). The aneurysm volume and volume variance were significantly smaller in the APMC reconstruction than those in the half-scan reconstruction (volume: 1107.2 +/- 1813.8 mm(3) vs 1135.1 +/- 1853.8 mm(3); p < 0.05; coefficient of variation: 0.0291 +/- 0.014 vs 0.0463 +/- 0.026, p < 0.05, respectively). CONCLUSION: Our results show that APMC reduces the reconstruction related misregistration between the cardiac phases compared to half-scan reconstruction. PMID- 27379503 TI - Microvascular function, is there a link to myocardial viability: Is this another piece to the puzzle? PMID- 27379504 TI - Age-related changes in the brain antioxidant status: modulation by dietary supplementation of Decalepis hamiltonii and physical exercise. AB - The synergistic effects of physical exercise and diet have profound benefits on brain function. The present study was aimed to determine the effects of exercise and Decalepis hamiltonii (Dh) on age-related responses on the antioxidant status in discrete regions of rat brain. Male Wistar albino rats of 4 and 18 months old were orally supplemented with Dh extract and swim trained at 3 % intensity for 30 min/day, 5 days/week, for a period of 30 days. Supplementation of 100 mg Dh aqueous extract/kg body weight and its combination with exercise significantly elevated the antioxidant enzyme activities irrespective of age. Age-related and region-specific changes were observed in superoxide levels, and protein carbonyl and malondialdehyde contents, and were found to be decreased in both trained and supplemented groups. Levels of total thiols, protein, and nonprotein thiols decreased with age and significantly increased in the SW-T(+100 mg) groups. Our results demonstrated that the interactive effects of two treatments enhanced the antioxidant status and decreased the risk of protein and lipid oxidation in the rat brain. PMID- 27379505 TI - Age-dependent modulation of fasting and long-term dietary restriction on acetylcholinesterase in non-neuronal tissues of mice. AB - Dietary restriction (DR) without malnutrition is a robust intervention that extends lifespan and slows the onset of nervous system deficit and age-related diseases in diverse organisms. Acetylcholinesterase (AChE), a thoroughly studied enzyme better known for hydrolyzing acetylcholine (ACh) in neuronal tissues, has recently been linked with multiple unrelated biological functions in different non-neuronal tissues. In the present study, the activity and protein expression level of AChE in liver, heart, and kidney of young (1 month), adult (6 month), and aged (18 month) mice were investigated. We also studied age- and tissue specific changes in AChE activity and protein expression level after the mice were subjected to 24-h fasting and long-term DR. Our results showed that AChE activity and protein expression in kidney and heart of aged mice decreased significantly in comparison with young mice. On the contrary, long-term DR decreases the AChE activity and the protein expression level in all tissues irrespective of ages studied. We summarized that changes in AChE with age in different tissues studied reflects its different roles at different phases of an organism's life. Conversely, the cumulative modulation manifested in the form of lowering AChE by long-term DR may prevent the futile synthesis and accumulation of unwanted AChE besides the added compensatory benefit of enhanced ACh availability needed during the period of starvation. This, in turn, may help in preventing the declining homeostatic roles of this important neurotransmitter in different tissues. PMID- 27379506 TI - Graft placement with an omental flap for ruptured infective common iliac aneurysm in a patient with a continuous flow left ventricular assist device: alternative surgical approach avoiding driveline injury and pathogen identification by 16S ribosomal DNA gene analysis. AB - Patients supported by mechanical circulatory support have to wait for longer periods for heart transplantation in Japan. Infective events are a major complication and influence survival. Here, we present the case of a patient with an implantable left ventricular assist device for 6 months who had the complication of ruptured infective common iliac aneurysm. Graft placement with an omental flap was successfully performed via the alternative surgical approach to avoid percutaneous driveline injury. In samples of aortic specimens, 16S ribosomal DNA gene analysis identified Helicobacter cinaedi. Complete removal of the infected tissue and correct pathogen identification may have been relevant to the good clinical course. PMID- 27379507 TI - Improving health care communication for caregivers: A pilot study. AB - With the growing older adult population, there will also be more informal caregivers assisting friends and family with their health care. With the increasing complexity of health care, improved caregiver communication skills have the potential to reduce caregiver burden and frustration and improve care recipient health. The primary goal of this project was to develop and refine the content and teaching methods of a small-group behavioral change program to improve communication between caregivers of older adults and health care professionals. The authors developed the Care Talks program for improving communication between caregivers and health care professionals. They conducted a prospective cohort feasibility study of the intervention to assess caregiver communication confidence at baseline and one month postintervention. Six participants were enrolled. Of the 15 participants who answered the question, 15 (100%) would recommend this program to a friend. There was significant improvement in a 10-question composite of communication confidence pre/post scores from 74.1 to 79.6 p = .03. This small-group behavioral change intervention significantly improved communication confidence for this sample of caregivers. Further research is needed to determine the long-term effects of this program on caregivers and care recipients. PMID- 27379508 TI - Effects of Fibronectin Coating on Bacterial and Osteoblast Progenitor Cells Adherence in a Co-culture Assay. AB - Bacterial adherence to the surface of implants functionalized with cell-adhesive biomolecules is a critical first step of infection development. This study was designed to determine how the immobilization of human plasmatic fibronectin (pFN) could impact bacterial and osteoblast cells interaction with the surface during concomitant exposition to the two cell-types. Calibrated suspensions of P. aeruginosa PAOI or S. aureus CIP4.83 bacteria and STRO-1+A osteoblast progenitor cells were mixed, co-seeded on glass coverslips coated or not with pFN and incubated at 37 degrees C. After 3 h of co-culture, the presence of bacteria did not modify the STRO-1+A cells adherence to glass. pFN coating significantly enhanced STRO-1+A cells, CIP4.83 and PAOI adherence to glass and bacterial interaction with STRO-1+A cells. Confocal laser scanning microscopy observations revealed that cells on the pFN-coated substrate exhibited a greater spreading, better organized network of cytoskeletal filaments, and an increased cellular FN expression than cells on the uncoated substrate. The use of fluorescently labeled pFN showed that adherent STRO-1+A cells were able to remodel and to concentrate coated pFN at the cells surface. Thus, the use of FN coating could increase the risk of bacterial adherence to the material surface, acting either directly onto the coating layer or indirectly on adherent osteoblastic cells. This may increase the infection risk in the presence of bacterial contamination. PMID- 27379511 TI - [Not Available]. PMID- 27379510 TI - [Not Available]. PMID- 27379509 TI - The alpha-1 adrenoceptor (ADRA1A) genotype moderates the magnitude of acute cocaine-induced subjective effects in cocaine-dependent individuals. AB - OBJECTIVES: We examined whether a functional variant of the ADRA1A gene moderated cocaine-induced subjective effects in a group of cocaine-dependent individuals. METHODS: This study was a within-participant, double-blind, placebo-controlled inpatient human laboratory evaluation of 65 nontreatment-seeking, cocaine dependent [Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM IV)] individuals aged 18-55 years. Participants received both placebo (saline, IV) and cocaine (40 mg, IV), and subjective responses were assessed 15 min before receiving an infusion and at 5 min intervals for the subsequent 20 min. The rs1048101 variant of the alpha1A-adrenoceptor (ADRA1A) gene was genotyped and it was evaluated whether the Cys to Arg substitution at codon 347 in exon 2 (Cys347Arg) moderated the magnitude of the subjective effects produced by cocaine. RESULTS: Thirty (46%) participants were found to have the major allele CC genotype and 35 (44%) carried at least one minor T-allele of rs1048101 (TT or TC genotype). Individuals with the CC genotype showed greater responses for 'desire' (P<0.0001), 'high' (P<0.0001), 'any drug effect' (P<0.0001), 'like cocaine' (P<0.0001), and 'likely to use cocaine if given access' (P<0.05) with experiment-wise significance. CONCLUSION: This study indicates that the ADRA1A genotype could be used to identify individuals for whom acute cocaine exposure may be more rewarding and by inference may result in greater difficulty in establishing and/or maintaining abstinence from cocaine. PMID- 27379512 TI - [Not Available]. PMID- 27379513 TI - [Not Available]. PMID- 27379514 TI - [Not Available]. PMID- 27379515 TI - [Not Available]. PMID- 27379517 TI - Arterial spin labeling perfusion predicts longitudinal decline in semantic variant primary progressive aphasia. AB - The objective of the study was to evaluate the prognostic value of regional cerebral blood flow (CBF) measured by arterial spin labeled (ASL) perfusion MRI in patients with semantic variant primary progressive aphasia (svPPA). We acquired pseudo-continuous ASL (pCASL) MRI and whole-brain T1-weighted structural MRI in svPPA patients (N = 13) with cerebrospinal fluid biomarkers consistent with frontotemporal lobar degeneration pathology. Follow-up T1-weighted MRI was available in a subset of patients (N = 8). We performed whole-brain comparisons of partial volume-corrected CBF and cortical thickness between svPPA and controls, and compared baseline and follow-up cortical thickness in regions of significant hypoperfusion and hyperperfusion. Patients with svPPA showed partial volume-corrected hypoperfusion relative to controls in left temporal lobe and insula. svPPA patients also had typical cortical thinning in anterior temporal, insula, and inferior frontal regions at baseline. Volume-corrected hypoperfusion was seen in areas of significant cortical thinning such as the left temporal lobe and insula. Additional regions of hypoperfusion corresponded to areas without cortical thinning. We also observed regions of hyperperfusion, some associated with cortical thinning and others without cortical thinning, including right superior temporal, inferior parietal, and orbitofrontal cortices. Regions of hypoperfusion and hyperperfusion near cortical thinning at baseline had significant longitudinal thinning between baseline and follow-up scans, but perfusion changes in distant areas did not show progressive thinning. Our findings suggest ASL MRI may be sensitive to functional changes not readily apparent in structural MRI, and specific changes in perfusion may be prognostic markers of disease progression in a manner consistent with cell-to-cell spreading pathology. PMID- 27379516 TI - Activation-Induced TIM-4 Expression Identifies Differential Responsiveness of Intestinal CD103+ CD11b+ Dendritic Cells to a Mucosal Adjuvant. AB - Macrophage and dendritic cell (DC) populations residing in the intestinal lamina propria (LP) are highly heterogeneous and have disparate yet collaborative roles in the promotion of adaptive immune responses towards intestinal antigen. Under steady-state conditions, macrophages are efficient at acquiring antigen but are non-migratory. In comparison, intestinal DC are inefficient at antigen uptake but migrate to the mesenteric lymph nodes (mLN) where they present antigen to T cells. Whether such distinction in the roles of DC and macrophages in the uptake and transport of antigen is maintained under immunostimulatory conditions is less clear. Here we show that the scavenger and phosphatidylserine receptor T cell Immunoglobulin and Mucin (TIM)-4 is expressed by the majority of LP macrophages at steady-state, whereas DC are TIM-4 negative. Oral treatment with the mucosal adjuvant cholera toxin (CT) induces expression of TIM-4 on a proportion of CD103+ CD11b+ DC in the LP. TIM-4+ DC selectively express high levels of co-stimulatory molecules after CT treatment and are detected in the mLN a short time after appearing in the LP. Importantly, intestinal macrophages and DC expressing TIM-4 are more efficient than their TIM-4 negative counterparts at taking up apoptotic cells and soluble antigen ex vivo. Taken together, our results show that CT induces phenotypic changes to migratory intestinal DC that may impact their ability to take up local antigens and in turn promote the priming of mucosal immunity. PMID- 27379518 TI - Risks and Population Burden of Cardiovascular Diseases Associated with Diabetes in China: A Prospective Study of 0.5 Million Adults. AB - BACKGROUND: In China, diabetes prevalence is rising rapidly, but little is known about the associated risks and population burden of cardiovascular diseases. We assess associations of diabetes with major cardiovascular diseases and the relevance of diabetes duration and other modifiable risk factors to these associations. METHODS AND FINDINGS: A nationwide prospective study recruited 512,891 men and women aged 30-79 y between 25 June 2004 and 15 July 2008 from ten diverse localities across China. During ~7 y of follow-up, 7,353 cardiovascular deaths and 25,451 non-fatal major cardiovascular events were recorded among 488,760 participants without prior cardiovascular disease at baseline. Cox regression yielded adjusted hazard ratios (HRs) comparing disease risks in individuals with diabetes to those without. Overall, 5.4% (n = 26,335) of participants had self-reported (2.7%) or screen-detected (2.7%) diabetes. Individuals with self-reported diabetes had an adjusted HR of 2.07 (95% CI 1.90 2.26) for cardiovascular mortality. There were significant excess risks of major coronary event (2.44, 95% CI 2.18-2.73), ischaemic stroke (1.68, 95% CI 1.60 1.77), and intracerebral haemorrhage (1.24, 95% CI 1.07-1.44). Screen-detected diabetes was also associated with significant, though more modest, excess cardiovascular risks, with corresponding HRs of 1.66 (95% CI 1.51-1.83), 1.62 (95% CI 1.40-1.86), 1.48 (95% CI 1.40-1.57), and 1.17 (95% CI 1.01-1.36), respectively. Misclassification of screen-detected diabetes may have caused these risk estimates to be underestimated, whilst lack of data on lipids may have resulted in residual confounding of diabetes-associated cardiovascular disease risks. Among individuals with diabetes, cardiovascular risk increased progressively with duration of diabetes and number of other presenting modifiable cardiovascular risk factors. Assuming a causal association, diabetes now accounts for ~0.5 million (489,676, 95% CI 335,777-681,202) cardiovascular deaths annually in China. CONCLUSIONS: Among Chinese adults, diabetes is associated with significantly increased risks of major cardiovascular diseases. The increasing prevalence and younger age of onset of diabetes foreshadow greater diabetes attributable disease burden in China. PMID- 27379519 TI - Analysis of recombination QTLs, segregation distortion, and epistasis for fitness in maize multiple populations using ultra-high-density markers. AB - KEY MESSAGE: Using two nested association mapping populations and high-density markers, some important genomic regions controlling recombination frequency and segregation distortion were detected. Understanding the maize genomic features would be useful for the study of genetic diversity and evolution and for maize breeding. Here, we used two maize nested association mapping (NAM) populations separately derived in China (CN-NAM) and the US (US-NAM) to explore the maize genomic features. The two populations containing 36 families and about 7000 recombinant inbred lines were evaluated with genotyping-by-sequencing. Through the comparison between the two NAMs, we revealed that segregation distortion is little, whereas epistasis for fitness is present in the two maize NAM populations. When conducting quantitative trait loci (QTL) mapping for the total number of recombination events, we detected 14 QTLs controlling recombination. Using high-density markers to identify segregation distortion regions (SDRs), a total of 445 SDRs were detected within the 36 families, among which 15 common SDRs were found in at least ten families. About 80 % of the known maize gametophytic factors (ga) genes controlling segregation distortion were overlapped with highly significant SDRs. In addition, we also found that the regions with high recombination rate and high gene density usually tended to have little segregation distortion. This study will facilitate population genetic studies and gene cloning affecting recombination variation and segregation distortion in maize, which can improve plant breeding progress. PMID- 27379520 TI - Molecular Characterization and Transcriptional Regulation Analysis of the Bovine PDHB Gene. AB - The pyruvate dehydrogenase beta subunit (PDHB) is a subunit of pyruvate dehydrogenase (E1), which catalyzes pyruvate into acetyl-CoA and provides a linkage between the tricarboxylic acid cycle (TCA) and the glycolysis pathway. Previous studies demonstrated PDHB to be positively related to the intramuscular fat (IMF) content. However, the transcriptional regulation of PDHB remains unclear. In our present study, the cDNA of bovine PDHB was cloned and the genomic structure was analyzed. The phylogenetic tree showed bovine PDHB to be closely related to goat and sheep, and least related to chicken. Spatial expression pattern analysis revealed the products of bovine PDHB to be widely expressed with the highest level in the fat of testis. To understand the transcriptional regulation of bovine PDHB, 1899 base pairs (bp) of the 5'-regulatory region was cloned. Sequence analysis neither found consensus TATA-box nor CCAAT-box in the 5'-flanking region of bovine PDHB. However, a CpG island was predicted from nucleotides -284 to +117. Serial deletion constructs of the 5'-flanking region, evaluated in dual-luciferase reporter assay, revealed the core promoter to be located 490bp upstream from the transcription initiation site (+1). Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation assay (ChIP) in combination with asite-directed mutation experiment indicated both myogenin (MYOG) and the CCAAT/enhancer-binding protein beta (C/EBPbeta) to be important transcription factors for bovine PDHB in skeletal muscle cells and adipocytes. Our results provide an important basis for further investigation of the bovine PDHB function and regulation in cattle. PMID- 27379521 TI - Gender Disparities in the Prevalence of Undernutrition and the Higher Risk among the Young Women of Indian Tribes. AB - BACKGROUND: High undernutrition is a grave concern in India. Marginalized populations like Indian tribes have been under the serious stress of such nutritional extreme. Women, in particular, are the worst sufferers. Gender related comprehensive studies regarding the prevalence and risks of undernutrition among the tribes have not been properly pursued in India; the vulnerability of the young females has least been examined. METHODS AND FINDINGS: We conducted a cross-sectional study during January 2011 to December 2013 among 1066 males and 1090 females (n = 2156) in the 20-60 years age group belonging to the nine major tribes; Santals, Oraons and Koras (West Bengal): Santals, Bhumijs and Bathudis (Odisha): Dhodias, Kuknas and Chaudharis (Gujarat). The undernutrition burden was estimated and such risks were analyzed for the women in comparison to the men. The overall undernutrition among the females was found to be 47.4% (95% CI 44.4-50.4) against 32.1% (95% CI 29.3-34.9) among males, indicating about a half of the female population undernourished. The odds of risks for underweight status among females were observed to be high in comparison to males with an odds of 1.9 (95% CI, 1.6-2.2; p<=0.001) for the overall undernutrition category, 1.7 (95% CI, 1.3-2.3; p<=0.001) for the mild undernutrition category, 1.3 (95% CI, 1.1-1.6; p<=0.01) for combined moderate and mild undernutrition category and 3.3 (95% CI at 2.3-4.6; p<=0.001) for severe undernutrition category. The young females were observed with a high prevalence of undernutrition along with increased risk. The 30-year mean BMI trend of the Indian population in comparison to the males, females, and overall tribal population places the tribal females at the highest risk. CONCLUSION: Indian tribes are suffering from the higher prevalence of undernutrition by further highlighting a high gender bias. The health and empowerment of adolescent and young tribal girls needs additional focus. Overall, no remarkable control on undernutrition has been achieved among Indian tribes despite various efforts. PMID- 27379522 TI - Estradiol Exposure Differentially Alters Monolayer versus Microtissue MCF-7 Human Breast Carcinoma Cultures. AB - The development of three-dimensional (3D) cultures is increasing, as they are able to provide the utility of in vitro models and the strength of testing in physiologically relevant systems. When cultured in a scaffold-free agarose hydrogel system, MCF-7 human breast carcinoma cells organize and develop into microtissues that contain a luminal space, in stark contrast to the flat morphology of MCF-7 two-dimensional (2D) monolayer cultures. Following exposure to 1nM E2, expression of typical estrogen-responsive genes, including progesterone receptor (PGR), PDZ containing domain 1 (PDZK1) and amphiregulin (AREG) is increased in both 2D and 3D cultures. When examining expression of other genes, particularly those involved in cell adhesion, there were large changes in 3D MCF-7 microtissues, with little to no change observed in the MCF-7 monolayer cultures. Together, these results indicate that while the initial estrogen-regulated transcriptional targets respond similarly in 2D and 3D cultures, there are large differences in activation of other pathways related to cell-cell interactions. PMID- 27379523 TI - Issues in Developing and Evaluating a Culturally Tailored Internet Cancer Support Group. AB - The purpose of this article is to explore practical issues in developing and implementing a culturally tailored Internet Cancer Support Group for a group of ethnic minority patients with cancer-Asian Americans. Throughout the research process of the original study testing the Internet cancer support group, the research team made written records of practical issues and plausible rationales for the issues. Weekly group discussion among research team members was conducted, and the discussion records were evaluated and analyzed using a content analysis (with individual words as the unit of analysis). The codes from the analysis process were categorized into idea themes, through which the issues were extracted. The issues included those in (1) difficulties in using multiple languages, (2) collaboration with the information technology department and technical challenges, (3) difficulties in recruitment, (4) difficulties in retention, (5) optimal timing, and (6) characteristics of the users. Based on the findings, we suggest that researchers plan a workable translation process, check technical needs in advance, use multiple strategies to recruit and retain research participants, plan the right time for data collection, and consider characteristics of the users in the study design. PMID- 27379524 TI - Development of a Tobacco Cessation Clinical Decision Support System for Pediatric Emergency Nurses. AB - Almost 50% of children who visit the pediatric emergency department are exposed to tobacco smoke. However, pediatric emergency nurses do not routinely address this issue. The incorporation of a clinical decision support system into the electronic health record may improve the rates of tobacco exposure screening and interventions. We used a mixed-methods design to develop, refine, and implement an evidence-based clinical decision support system to help nurses screen, educate, and assist caregivers to quit smoking. We included an advisory panel of emergency department experts and leaders and focus and user groups of nurses. The prompts include the following: (1) "Ask" about child smoke exposure and caregiver smoking; (2) "Advise" caregivers to reduce their child's smoke exposure by quitting smoking; (3) "Assess" interest; and (4) "Assist" caregivers to quit. The clinical decision support system was created to reflect nurses' suggestions and was implemented in five busy urgent care settings with 38 nurses. The nurses reported that the system was easy to use and helped them to address caregiver smoking. The use of this innovative tool may create a sustainable and disseminable model for prompting nurses to provide evidence-based tobacco cessation treatment. PMID- 27379525 TI - HtrA1 Proteolysis of ApoE In Vitro Is Allele Selective. AB - Apolipoprotein E (ApoE) belongs to a large class of proteins that solubilize lipids for physiological transport. Humans have three different APOE alleles, APOE epsilon2, APOE epsilon3, and APOE epsilon4, and genetic studies identified ApoE4 as the strongest genetic risk factor for Alzheimer's disease (AD). People who are homozygous for ApoE4 (i.e., ApoE4/E4) are an order of magnitude more likely to develop late-onset AD (LOAD) than ApoE3/E3 carriers. Several differences between ApoE3 and ApoE4 may contribute to AD including the observation that ApoE4 is degraded to a greater extent than ApoE3 in the human brain. Experiments with high-temperature requirement serine peptidase A1 (HtrA1), which is found in the nervous system, demonstrate that HtrA1 is an allele selective ApoE-degrading enzyme that degrades ApoE4 more quickly than ApoE3. This activity is specific to HtrA1, as similar assays with HtrA2 showed minimal ApoE4 proteolysis and trypsin had no preference between ApoE4 and ApoE3. HtrA1 has also been reported to cleave the tau protein (Tau) and the amyloid protein precursor (APP) to hinder the formation of toxic amyloid deposits associated with AD. Competition assays with ApoE4, ApoE3, and Tau revealed that ApoE4 inhibits Tau degradation. Thus, the identification of ApoE4 as an in vitro HtrA1 substrate suggests a potential biochemical mechanism that links ApoE4 regulation of AD proteins such as Tau. PMID- 27379527 TI - Intraventricular Hemorrhage and Platelet Indices in Extremely Premature Neonates. AB - Intraventricular hemorrhage (IVH) is a multifactorial disorder, the most important risk factors of which are prematurity and low birth weight. Disturbances in cerebral blood flow, inherent fragility of the germinal matrix vasculature, and platelet/coagulation disturbances are the 3 major pathogenic mechanisms. In this context, we investigated the role of platelet indices and several maternal and neonatal characteristics in the development of IVH through a retrospective cohort analysis of 130 extremely premature neonates, 24% of whom presented with severe IVH. There was a significant difference in platelet counts between the IVH and the control group on the first day of life (P=0.046). Presence of IVH was linked with lower birth weight (P=0.006) and lower gestational age (P=0.001). Platelet count on the first day of life was positively correlated with survival (P=0.001) and, along with platelet mass, was indicative of the worst IVH grade recorded for each neonate (P=0.002 and 0.007, respectively). Prolonged prothrombin time was also correlated with IVH (P<0.001), but factor analysis supported no prominent role. Maternal medications seem to play a minor role as well. In conclusion, IVH in extremely premature infants cannot be solely explained by platelet parameters, and further studies are required to determine the relationships between IVH, platelet indices, and outcomes. PMID- 27379526 TI - Nonplanar Monocyanines: Meso-Substituted Thiazole Orange with High Photostability and Their Synthetic Strategy as well as a Cell Association Study. AB - A convenient approach for the direct synthesis of meso-substituted thiazole orange (meso-TO) analogues has been unprecedentedly developed through the AlCl3 catalyzed reaction of parent TO with benzyl alcohol derivatives. Single-crystal X ray structures show that the prepared new meso-TO analogues are nonplanar, forming a sharp contrast to planar TO. The spectral properties show that nonplanar meso-TO analogues do not aggregate, existing in monomer form (M) in PBS buffer, and have little effect of solvatochromism in different solvents. In comparison with the parents, meso-TO analogues exhibit a large Stokes shift, excellent light fastness, and inertness to singlet oxygen. A cellular association study demonstrates that incorporation of a benzyl group at the meso position methine of parent TO can decrease the cytotoxicity, change staining area in cells, and emit long-wavelength fluorescence for an extended time, which are useful for the development of smarter TOs for imaging in biological science. PMID- 27379528 TI - Effect of Everolimus (RAD001) on Acute Graft-Versus-Host Disease in Mice. PMID- 27379529 TI - Transcranial Doppler Screening in a Regional Care Network for Sickle Cell Disease in the United Kingdom. AB - The risk of stroke in children screened with transcranial Doppler ultrasound in the United Kingdom is not known. We evaluated a clinician-led program using a risk assessment modified from the STOP protocol. High-risk classification included abnormal velocities in the anterior cerebral artery, and single abnormal scan if initial velocity >220 cm/s (high abnormal) or if preceded by at least 2 conditional scans. In total, 1653 scans were performed in 542 children, followed for 2235 patient-years. Fifty-eight (10.7%) high-risk subjects were identified, including 18 (31%) with high abnormal, and 15 (26%) with previous conditional scans. In 2 (3%), abnormal velocity was restricted to the anterior cerebral artery. The estimated proportion of children at high risk, scanned before 6 years of age was >20%. There were 4 cases of acute ischemic stroke (AIS) and 2 of acute hemorrhagic stroke. The incidence of all stroke, AIS, and acute hemorrhagic stroke were 0.27, 0.18, and 0.09 per 100 patient-years, respectively. The proportion of children at high risk is higher than most previous estimates, partly as a result of our modified risk assessment. About 2 children per 1000 screened with transcranial Doppler ultrasound progress to AIS. PMID- 27379530 TI - Outcome of Nephroblastoma Treatment According to the SIOP-2001 Strategy at a Single Institution in Argentina. AB - OBJECTIVE: Wilms tumor (WT) is a disease with a good prognosis. The aim of this study was to evaluate the outcome of patients with WT, treated according to the SIOP-2001 strategy. METHODS: A retrospective analysis of 141 consecutive patients with WT diagnosed at our institution between December 2001 and 2013 was performed. RESULTS: A total of 114 patients, median age 38.8 months (3 to 155 mo), were assessable for analysis. Fine-needle aspiration was initially performed in 88 patients (84.6%). Stage distribution was: I: 33%, II: 9.6%, III: 28%, IV: 14%, V: 14.9%. Six patients were stage III because of tumor spillage. The remaining patients received preoperative chemotherapy. Adjuvant chemotherapy was given without randomization, using vincristine-actinomycin for stage II and vincristine-doxorubicin-actinomycin plus radiotherapy for stage III. After a median follow-up of 52 months, 5-year overall survival and event-free survival were 91% and 85%, respectively. Overall survival according to stage was: I: 96%, II: 99%, III: 88%, IV: 78%, V: 90% (P=0.16). There was no significant difference in event-free survival (P=0.7). Seventy-eight (85.7%) were intermediate-risk and 11 (12%) were high-risk patients. Seventeen patients (14.9%) relapsed within 2 to 99 months (median 29.9 mo). Eight patients (7%) died of progressive disease. There were no treatment-related deaths. CONCLUSIONS: The SIOP-01 protocol proposes a treatment strategy that is feasible in our institution, achieving good results. PMID- 27379531 TI - Fatal Pulmonary Embolism Due to Inherited Thrombophilia Factors in a Child With Wolfram Syndrome. AB - Wolfram syndrome-1 is a rare and severe autosomal recessive neurodegenerative disease characterized by diabetes mellitus (DM), optic atrophy, diabetes insipidus, and deafness. Poorly controlled type 1 DM increases the risk for thrombosis. However, coexistence of DM and hereditary thrombosis factors is rarely observed. Here we present the case of a 13.5-year-old, nonfollowed girl newly diagnosed with poorly controlled Wolfram syndrome on the basis of the results of clinical and laboratory examinations. On the eighth day after diabetic ketoacidosis treatment, pulmonary embolism developed in the subject. Thrombus identified in the right atrium using echocardiography was treated by emergency thrombectomy. Homozygous mutation in the methylenetetrahydrofolate reductase gene C677T, heterozygous factor-V Leiden mutation, and active protein C resistance were identified in the patient. The patient was lost because of a recurring episode of pulmonary embolism on the 86th day of hospitalization. We present this case to highlight the need for investigating hereditary thrombosis risk factors in diabetic patients in whom thromboembolism develops. PMID- 27379532 TI - Demographic History and Reproductive Output Correlates with Intraspecific Genetic Variation in Seven Species of Indo-Pacific Mangrove Crabs. AB - The spatial distribution and the amount of intraspecific genetic variation of marine organisms are strongly influenced by many biotic and abiotic factors. Comparing biological and genetic data characterizing species living in the same habitat can help to elucidate the processes driving these variation patterns. Here, we present a comparative multispecies population genetic study on seven mangrove crabs co-occurring in the West Indian Ocean characterized by planktotrophic larvae with similar pelagic larval duration. Our main aim was to investigate whether a suite of biological, behavioural and ecological traits could affect genetic diversities of the study species in combination with historical demographic parameters. As possible current explanatory factors, we used the intertidal micro-habitat colonised by adult populations, various parameters of individual and population fecundity, and the timing of larval release. As the genetic marker, we used partial sequences of cytochrome oxidase subunit I gene. Genetic and ecological data were collected by the authors and/or gathered from primary literature. Permutational multiple regression models and ANOVA tests showed that species density and their reproductive output in combination with historical demographic parameters could explain the intraspecific genetic variation indexes across the seven species. In particular, species producing consistently less eggs per spawning event showed higher values of haplotype diversity. Moreover, Tajima's D parameters well explained the recorded values for haplotype diversity and average gammast. We concluded that current intraspecific gene diversities in crabs inhabiting mangrove forests were affected by population fecundity as well as past demographic history. The results were also discussed in terms of management and conservation of fauna in the Western Indian Ocean mangroves. PMID- 27379533 TI - Relation of unprocessed, processed red meat and poultry consumption to blood pressure in East Asian and Western adults. AB - BACKGROUND: Epidemiologic evidence suggests that relationships of red meat consumption with risk of cardiovascular diseases depends on whether or not the meat is processed, including addition of preservatives, but evidence is limited for blood pressure (BP). OBJECTIVE: To examine cross-sectional associations with BP of unprocessed and processed red meat and poultry consumption, total and by type, using data from the INTERnational study on MAcro/micronutrients and blood Pressure. DESIGN: INTERnational study on MAcro/micronutrients and blood Pressure included 4680 men and women ages 40-59 years from 17 population samples in Japan, China, the United Kingdom, and the United States. During four visits, eight BP measurements, four multipass 24-h dietary recalls, and two timed 24-h urine samples were collected. RESULTS: Average daily total unprocessed/processed meat consumption (g/1000 kcal) was 20/5 in East Asian and 38/21 in Western participants. Unprocessed meat intakes comprised red meat for 75% in East Asian and 50% in Western participants. In Westerners, multiple linear regression analyses showed SBP/DBP differences for total unprocessed red meat consumption higher by 25 g/1000 kcal +0.74/+0.57 mmHg (P = 0.03/0.01) and for unprocessed poultry of +0.79/+0.16 mmHg (P = 0.02/0.50). Unprocessed red meat was not related to BP in East Asian participants. In Westerners, SBP/DBP differences for processed red meat higher by 12.5 g/1000 kcal were +1.20/+0.24 mmHg (P < 0.01/0.24), due to consumption of cold cuts and sausages (+1.59/+0.32 mmHg, P < 0.001/0.27). CONCLUSION: These findings are consistent with recommendations to limit meat intake (processed and unprocessed) to maintain and improve cardiovascular health. PMID- 27379534 TI - Oscillometric analysis compared with cardiac magnetic resonance for the assessment of aortic pulse wave velocity in patients with myocardial infarction. AB - OBJECTIVES: Measurement of aortic pulse wave velocity (PWV) is the gold standard for assessment of aortic stiffness. In patients with ST-segment elevation myocardial infarction (STEMI), high aortic PWV has deleterious effects on the myocardium. In the present study, we compared a novel oscillometric device with cardiac magnetic resonance (CMR) imaging for the assessment of aortic PWV in STEMI patients. METHODS: We measured aortic PWV in 60 reperfused STEMI patients using two different methods. The oscillometric method (PWVOSC) is based on mathematical transformation of brachial pressure waveforms, oscillometrically determined using a common cuff (Mobil-O-Graph, I.E.M., Stolberg, North Rhine Westphalia, Germany). Phase-contrast CMR imaging (1.5 T scanner, Siemens, Erlangen, Bavaria, Germany) at the level of the ascending and abdominal aorta was performed to determine CMR-derived pulse wave velocity with the use of the transit time method. RESULTS: The mean age of the study population was 57 +/- 11 years; 11 (18%) were women. Median PWVOSC was 7.4 m/s (interquartile range 6.8 8.9 m/s), and median CMR-derived pulse wave velocity was 6.3 m/s (interquartile range 5.7-8.2 m/s) (P < 0.001). A strong correlation was detected between both methods (r = 0.724, P < 0.001). Bland-Altman analysis revealed a bias of 0.62 m/s (upper and lower limit of agreement: 3.84 and -2.61 m/s). The coefficient of variation between both methods was 21%. CONCLUSION: In reperfused STEMI patients, aortic PWV assessed noninvasively by transformation of brachial pressure waveforms showed an acceptable agreement with the CMR-derived transit time method. PMID- 27379535 TI - Partial inhibition of activin receptor-like kinase 4 attenuates pressure overload induced cardiac fibrosis and improves cardiac function. AB - BACKGROUND: Activin receptor-like kinase 4 (ALK4), a downstream receptor of transforming growth factor-beta superfamily, is highly expressed in the mammal heart. Upregulated ALK4 expression and activated ALK4-small mother against decapentaplegic (Smad)2/3 signaling have been reported to play a pivotal role in tumorigenesis and in the development of systemic sclerosis. However, the role of ALK4-Smad2/3 pathway in the pathogenesis of cardiac hypertrophy and cardiac fibrosis remains unknown. METHODS AND RESULTS: In this study, the mice with heterozygous knocking out of ALK4 gene (ALK4) were generated and subjected to aortic banding for 4 weeks. We found that ALK4 expression was upregulated in aortic banding-induced model of cardiac hypertrophy and cardiac fibrosis in wild type mice. Compared with the wild-type mice, ALK4mice demonstrated a similar extent of aortic banding-induced cardiac hypertrophy, but a significant suppression of cardiac fibrosis to 64.8% of the basal level, and a subsequent amelioration in the cardiac dysfunction (left ventricle ejection fraction: 59.0 +/- 6.4 in wild-type mice vs. 75.6 +/- 3.9% in ALK4 mice; left ventricle end diastolic pressure: 16.6 +/- 4.7 mmHg in wild-type mice vs. 6.6 +/- 2.8 mmHg in ALK4 mice) associated with inhibition of cardiac fibroblast activation and cardiomyocyte apoptosis. In vitro, ALK4 haploinsufficiency blocked the cellular proliferation/differentiation and collagen production in cultured cardiac fibroblasts after angiotensin-II stimulation. Mechanistically, ALK4 haploinsufficiency resulted in the suppression of Smad2/3 activity. CONCLUSION: Our results demonstrate that ALK4 haploinsufficiency ameliorates cardiac fibrosis and dysfunction in a mouse pressure-overload model associated with inhibition of cardiac fibroblast activation and cardiomyocyte apoptosis through the suppression of Smad2/3 activity, and suggest that ALK4 is a novel therapeutic target in treating pressure overload-induced cardiac remodeling and heart failure. PMID- 27379536 TI - Catheter-based radio-frequency renal nerve denervation lowers blood pressure in obese hypertensive swine model. AB - OBJECTIVES: Radio-frequency renal denervation (RDN) therapy is under investigation for the treatment of uncontrolled hypertension. Data in hypertensive, drug-naive large animal models using RDN is limited. METHODS: A cohort of Ossabaw swine (N = 9) was implanted with telemetry monitors, enrolled on a high calorie-feed regimen and randomly assigned to RDN. Blood pressure (BP) data were separated and analyzed according to the following epoch definitions: 24 h (h), most-active-h, light-h, and dark-h. RESULTS: The mean weight increased by 45% from 86.5 +/- 2.5 kg at telemetry implant (day 87) to 125.2 +/- 4.5 kg at time of RDN therapy (day 227). Hypertension developed in all swine (24-h BP: 169.5/128.3 +/- 5.8/5.1 mmHg pre-RDN). RDN resulted in significant reductions in noradrenaline kidney tissue concentration by 63%. Significant BP reductions were documented at 45 days post-RDN in all defined interday epochs, except for the dark-h period. The most pronounced SBP/DBP reduction was 12.4/11.2 mmHg (P < 0.05), observed during the most-active-h period. Animals continued to gain weight after the RDN procedure to the end of the study at 90 days (125.2 +/- 4.5-138.5 +/- 6.6 kg, P < 0.001). At 90 days post-RDN, the mean 24-h BP returned near pre RDN baseline values. Given the strong relationship of BP to weight (R = 0.87, P < 0.001), group mean SBP/DBP was normalized by weight resulting in significant and continued reductions at both 45 and 90 days post-RDN across all intradaily epochs. CONCLUSION: Catheter-based RDN, using a multielectrode system, resulted in a significant reduction in 24-h BP in this drug-naive, hypertensive animal model. PMID- 27379537 TI - Parathyroid hormone, aldosterone-to-renin ratio and fibroblast growth factor-23 as determinants of nocturnal blood pressure in primary hyperparathyroidism: the eplerenone in primary hyperparathyroidism trial. AB - OBJECTIVES: The high prevalence of arterial hypertension in primary hyperparathyroidism (pHPT) is largely unexplained. Apart from parathyroid hormone (PTH), the mineral hormones fibroblast growth factor (FGF)-23 and aldosterone-to renin ratio (ARR) are upregulated in pHPT. We aimed to determine whether nocturnal blood pressure (BP) is related with PTH, FGF-23 or ARR in a relatively large sample of pHPT patients. METHODS: Cross-sectional data of the single-center "Eplerenone in Primary Hyperparathyroidism" trial were used. All patients with a biochemical diagnosis of pHPT who had both available 24-h ambulatory BP monitoring and valid laboratory data were included. RESULTS: Full data were available in 136 patients (mean age 67 +/- 10 years, 78% women). Median PTH was 99 (interquartile range: 82-124) pg/ml and mean calcium was 2.63 +/- 0.15 mmol/l. ARR, but not PTH or FGF-23, was significantly and directly related with nocturnal SBP (Pearson's r = 0.241, P < 0.01) and DBP (r = 0.328, P < 0.01). In multivariate regression analyses, with adjustment for age, sex, PTH, FGF-23, traditional cardiovascular risk factors, antihypertensive medication and parameters of calcium metabolism ARR remained significantly and directly related with nocturnal BP (SBP: adjusted beta-coefficient = 0.289, P < 0.01; DBP: beta = 0.399, P < 0.01). The relationship between ARR and nocturnal SBP was exclusively present in patients with PTH levels above the median of 99 pg/ml. CONCLUSION: ARR, but not FGF-23 or PTH, was independently and directly related with nocturnal BP parameters in patients with pHPT, and this relationship was dependent on pHPT disease severity. Inappropriately, elevated aldosterone may partially explain the high prevalence of arterial hypertension in pHPT. PMID- 27379538 TI - Gonadectomy prevents the increase in blood pressure and glomerular injury in angiotensin-converting enzyme 2 knockout diabetic male mice. Effects on renin angiotensin system. AB - BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) deletion worsens kidney injury, and its amplification ameliorates diabetic nephropathy. Male sex increases the incidence, prevalence, and progression of chronic kidney disease in our environment. METHOD: Here, we studied the effect of ACE2 deficiency and gonadectomy (GDX) on diabetic nephropathy and its relationship with fibrosis, protein kinase B (Akt) activation, and the expression of several components of the renin-angiotensin system (RAS).Mice were injected with streptozotocin to induce diabetes and followed for 19 weeks. Physiological and renal parameters were studied in wild-type and ACE2 knockout (ACE2KO) male mice with and without GDX. RESULTS: Diabetic ACE2KO showed increased blood pressure (BP), glomerular injury, and renal fibrosis compared with diabetic wild-type. Gonadectomized diabetic ACE2KO presented a decrease in BP. In the absence of ACE2, GDX attenuated albuminuria and renal lesions, such as mesangial matrix expansion and podocyte loss. Both, alpha-smooth muscle actin accumulation and collagen deposition were significantly decreased in renal cortex of gonadectomized diabetic ACE2KO but not diabetic wild-type mice. GDX also reduced circulating ACE activity in ACE2KO mice. Loss of ACE2 modified the effect of GDX on cortical gene expression of RAS in diabetic mice. Akt phosphorylation in renal cortex was increased by diabetes and loss of ACE2 and decreased by GDX in control and diabetic ACE2KO but not in wild-type mice. CONCLUSIONS: Our results suggest that GDX may exert a protective effect within the kidney under pathological conditions of diabetes and ACE2 deficiency. This renoprotection may be ascribed to different mechanisms such as decrease in BP, modulation of RAS, and downregulation of Akt related pathways. PMID- 27379539 TI - New-onset left atrial enlargement in a general population. AB - AIM: Increased left atrium diameter (LAD) is associated with elevated risk of cardiovascular morbidity and mortality. We evaluated new-onset left atrium enlargement (LAE) and their correlates over a 10-year period in participants of the general population enrolled in the Pressioni Monitorate e Loro Associazioni study. METHODS: The study included 1045 participants with normal LAD at baseline evaluation having a readable echocardiogram at the end of follow-up. Cut-points for abnormal LAD were derived from reference values recommended by American Society of Echocardiography. RESULTS: Over a 10-year period, 123 participants (11.8%) progressed to LAE. The incidence of new-onset LAE increased significantly from the lowest to the highest tertile of baseline office, home and 24-h blood pressure (BP); BMI; fasting blood glucose and left ventricular mass index (LVMI). In multivariate analysis, baseline LAD [odds ratio (OR) 3.18, confidence interval (CI) 2.26-4.47, P < 0.001], female sex (OR 3.68, CI 2.20-6.18, P < 0.001), office SBP (OR 1.36, CI 1.08-1.70, P = 0.008), BMI (OR 1.35, CI 1.07-1.69, P = 0.01 and LVMI (OR 1.29, CI 1.01-1.64, P = 0.04) emerged as key correlates of new-onset LAE. CONCLUSION: The study shows that in the population, long-term changes from normal LAD to LAE are independently driven by several risk factors such as the female sex and an increased baseline LAD, BMI, LVMI and BP, with no predictive superiority of home and ambulatory versus office values. Preventing BP elevations, overweight/obesity and left ventricular hypertrophy may thus all be important for LAE prevention. PMID- 27379540 TI - Pulse rate reactivity in childhood as a risk factor for adult hypertension: the 1970 British cohort study. AB - PURPOSE: Cardiovascular reactivity to mental stress has been used as a tool to predict short-term hypertension risk in adults but the impact of cardiovascular reactivity in childhood on hypertension in adulthood is unknown. Using the 1970 British Cohort study, we examined the association between pulse rate reactivity in childhood and risk of hypertension in adulthood. METHODS: A total of 6507 participants (51.6% women) underwent clinical examination at 10 years of age that involved measurement of blood pressure, BMI, and pulse rate pre and postexamination. Hypertension was ascertained by self-reported doctor diagnosis 32 years later at age 42. RESULTS: On average, there was a reduction in pulse rate after the medical examination (-1.2 +/- 8.2 bpm), although nearly a third of the sample recorded an increase in pulse rate of at least 3 bpm. A total of 488 (7.5%) study members developed hypertension at follow-up. After adjustment for a range of covariates, including resting blood pressure and BMI in childhood, a heightened pulse rate response to the examination (>=3 bpm) was associated with greater risk of hypertension in adulthood (odds ratio = 1.30, 95% confidence interval, 1.02, 1.67). The association persisted whether we modelled pulse rate as an absolute measure (postexamination) or a change score. CONCLUSION: These observational data suggest that elevated childhood cardiovascular reactivity could increase risk for hypertension in adulthood. PMID- 27379541 TI - Associations of blood pressure, sunlight, and vitamin D in community-dwelling adults. AB - BACKGROUND: Vitamin D deficiency/insufficiency is associated with hypertension. Blood pressure (BP) and circulating vitamin D concentrations vary with the seasons and distance from the equator suggesting BP varies inversely with the sunshine available (insolation) for cutaneous vitamin D photosynthesis. METHODS: To determine if the association between insolation and BP is partly explained by vitamin D, we evaluated 1104 participants in the Reasons for Racial and Geographic Differences in Stroke study whose BP and plasma 25-hydroxyvitamin D [25(OH)D] concentrations were measured. RESULTS: We found a significant inverse association between SBP and 25(OH)D concentration and an inverse association between insolation and BP in unadjusted analyses. After adjusting for other confounding variables, the association of solar insolation and BP was augmented, 0.3.5 +/- SEM 0.01 mmHg/1 SD higher solar insolation, P = 0.01. The greatest of effects of insolation on SBP were observed in whites (-5.2 +/- SEM 0.92 mmHg/1 SD higher solar insolation, P = 0.005) and in women (-3.8 +/- SEM 1.7 mmHg, P = 0.024). We found that adjusting for 25(OH)D had no effect on the association of solar insolation with SBP. CONCLUSION: We conclude that although 25(OH)D concentration is inversely associated with SBP, it did not explain the association of greater sunlight exposure with lower BP. PMID- 27379542 TI - Altered matrix metalloproteinase 9 and tissue inhibitor of metalloproteinases 1 levels in children with primary hypertension. AB - BACKGROUND: Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) are involved in cardiovascular remodeling in hypertension. Because metabolic abnormalities typical of metabolic syndrome is the dominant phenotype of primary hypertension in children, we hypothesized that MMP-9 and TIMP-1 plasma concentrations are altered in hypertensive children and correlate with metabolic abnormalities and target organ damage. METHOD: A total of 109 children (15.6, 10-17 years) with untreated primary hypertension were included to the study. The control group consisted of 74 healthy, normotensive children. RESULTS: Plasma MMP-9, TIMP-1 concentrations, and MMP-9/TIMP-1 ratio were significantly elevated in hypertensive boys in comparison with normotensive boys (P = 0.0001, P = 0.04, and P = 0.001, respectively), whereas there were no differences between hypertensive and normotensive girls. The levels of MMP-9 and TIMP-1 as well as MMP-9/TIMP-1 ratio were not associated either with hypertension stage, left ventricular hypertrophy, or carotid intima-media thickness. However, in a subgroup of 30 hypertensive patients in whom arterial stiffness was measured, TIMP-1 concentrations correlated with aortic pulse pressure (P < 0.05; r = 0.367), augmentation pressure (P < 0.05; r = 0.428), and augmentation index (P < 0.05; r = 0.404).Only hypertensive boys presented negative correlations of both MMP-9 and TIMP-1 levels with high-density lipoprotein cholesterol (r = 0.254, P = 0.01 and r = -0.241, P = 0.02, respectively). CONCLUSION: Hypertensive boys but not girls had elevated MMP-9 and TIMP-1 plasma concentrations, which indicates sex-related role of MMP/TIMP system in pediatric hypertension. The correlation between serum TIMP-1 and markers of arterial stiffness indicates on the involvement of TIMPs in arterial remodeling. PMID- 27379543 TI - Optoacoustic Imaging of Human Vasculature: Feasibility by Using a Handheld Probe. AB - Purpose To investigate whether multispectral optoacoustic tomography (MSOT) developed for deep-tissue imaging in humans could enable the clinical assessment of major blood vessels and microvasculature. Materials and Methods The study was approved by the Institutional Review Board of the University Medical Center Groningen (CCMO-NL-43587) and registered in the Dutch National Trial Registry (NTR4125). The authors designed a real-time handheld optoacoustic scanner for human use, based on a concave 8-MHz transducer array, attaining 135 degrees angular coverage. They applied a single-pulse-frame (SPF) sequence, which enabled motion insensitive optoacoustic imaging during handheld operation. SPF optoacoustic imaging was applied to imaging arteries and microvascular landmarks in the lower extremities of 10 healthy volunteers. The diameters selected microvessels were determined by measuring the full width at half maximum through the vessels in the MSOT images. Duplex ultrasonography was performed on the same landmarks in seven of the 10 volunteers for subjective comparison to the corresponding optoacoustic images. Results Optoacoustic imaging resolved blood vessels as small as 100 um in diameter and within 1 cm depth. Additionally, MSOT provided images reflecting hemoglobin oxygen saturation in blood vessels, clearly identifying arteries and veins, and was able to identify pulsation in arteries during imaging. Larger blood vessels, specifically the tibialis posterior and the dorsalis pedis arteries, were also visualized with MSOT. Conclusion Handheld MSOT was found to be capable of clinical vascular imaging, providing visualization of major blood vessels and microvasculature and providing images of hemoglobin oxygen saturation and pulsation. ((c)) RSNA, 2016. PMID- 27379545 TI - Correction: Suppression of USP18 Potentiates the Anti-HBV Activity of Interferon Alpha in HepG2.2.15 Cells via JAK/STAT Signaling. AB - [This corrects the article DOI: 10.1371/journal.pone.0156496.]. PMID- 27379544 TI - Comparison of Background Parenchymal Enhancement at Contrast-enhanced Spectral Mammography and Breast MR Imaging. AB - Purpose To assess the extent of background parenchymal enhancement (BPE) at contrast material-enhanced (CE) spectral mammography and breast magnetic resonance (MR) imaging, to evaluate interreader agreement in BPE assessment, and to examine the relationships between clinical factors and BPE. Materials and Methods This was a retrospective, institutional review board-approved, HIPAA compliant study. Two hundred seventy-eight women from 25 to 76 years of age with increased breast cancer risk who underwent CE spectral mammography and MR imaging for screening or staging from 2010 through 2014 were included. Three readers independently rated BPE on CE spectral mammographic and MR images with the ordinal scale: minimal, mild, moderate, or marked. To assess pairwise agreement between BPE levels on CE spectral mammographic and MR images and among readers, weighted kappa coefficients with quadratic weights were calculated. For overall agreement, mean kappa values and bootstrapped 95% confidence intervals were calculated. The univariate and multivariate associations between BPE and clinical factors were examined by using generalized estimating equations separately for CE spectral mammography and MR imaging. Results Most women had minimal or mild BPE at both CE spectral mammography (68%-76%) and MR imaging (69%-76%). Between CE spectral mammography and MR imaging, the intrareader agreement ranged from moderate to substantial (kappa = 0.55-0.67). Overall agreement on BPE levels between CE spectral mammography and MR imaging and among readers was substantial (kappa = 0.66; 95% confidence interval: 0.61, 0.70). With both modalities, BPE demonstrated significant association with menopausal status, prior breast radiation therapy, hormonal treatment, breast density on CE spectral mammographic images, and amount of fibroglandular tissue on MR images (P < .001 for all). Conclusion There was substantial agreement between readers for BPE detected on CE spectral mammographic and MR images. (c) RSNA, 2016. PMID- 27379546 TI - Mercury Release to Aquatic Environments from Anthropogenic Sources in China from 2001 to 2012. AB - Based on an analysis of measured data and distribution factors, we developed the China Aquatic Mercury Release (CAMR) model, which we used to calculate an inventory of mercury (Hg) that was released to aquatic environments from primary anthropogenic sources in China. We estimated a total release of 98 tons of Hg in 2012, including coal-fired power plants (17%), nonferrous metal smelting (33%), coal mining and washing (25%), domestic sewage (17%), and other sectors (8.3%). The total primary anthropogenic Hg released to aquatic environments in China decreased at an annual average rate of 1.7% between 2001 and 2012, even though GDP grew at an annual average rate of 10% during this period. In addition to the Hg that was released to aquatic environments in China's provinces, we estimated the Hg release amounts and intensities (in g/km(2).yr) for China's 58 secondary river basins. The highest aquatic Hg release intensities in China were associated with industrial wastewater on the North China Plain and domestic sewage in eastern China and southern China. We found that the overall uncertainty of our inventory ranges from -22% to 32%. We suggest that the inventory provided by this study can help establish a more accurate map of regional and global Hg cycling; it also has implications for water quality management in China. PMID- 27379547 TI - Primary treatment of idiopathic sudden sensorineural hearing loss with intratympanic dexamethasone. AB - PURPOSE OF REVIEW: Systemic corticosteroids have been the mainstay of treatment of idiopathic sudden sensorineural hearing loss (ISSNHL) for over 30 years. Recently, intratympanic steroids have risen in popularity; however, there is no consensus regarding the details of their application. The purpose of this article is to review the current literature and share our opinion that intratympanic dexamethasone (alone or with systemic steroids) should be offered as primary treatment of ISSNHL. RECENT FINDINGS: Intratympanic steroids have been shown to result in higher inner ear concentrations than systemic steroids in animal and human studies. Primary treatment of ISSNHL with intratympanic steroids in combination with systemic steroids has been demonstrated to result in better hearing outcomes than systemic steroids alone. Recent evidence has revealed these hearing outcomes to be dependent on the dose of intratympanic steroid. Dexamethasone may be better absorbed than methylprednisolone, and potentially offer a greater benefit. Furthermore, intratympanic steroids provide an effective alternative for patients who cannot tolerate systemic steroids. SUMMARY: Intratympanic dexamethasone alone, or in combination with systemic steroids, provides effective treatment of ISSNHL and should be utilized as primary treatment. Further investigation is required to determine the optimal choice, concentration, and administration schedule of intratympanic steroids. PMID- 27379548 TI - Management of sudden sensorineural hearing loss. AB - PURPOSE OF REVIEW: Sudden sensorineural hearing loss (SNHL) is an otologic emergency and should be managed quickly and effectively. This review focuses on the management of sudden SNHL, primarily idiopathic sudden SNHL as it is the most common cause. RECENT FINDINGS: Management options include observation, oral steroids, intratympanic steroids, or combined oral/intratympanic steroids. One third to two-thirds of patients will achieve spontaneous recovery, most likely within the first 2 weeks. Despite the lack of randomized controlled trials on steroid therapy efficacy, all patients should be offered steroid treatment given low risk and possible significant benefits. All patients should undergo MRI with gadolinium to rule out retrocochlear disorder. Bilateral sudden hearing loss should alert the clinician to possible systemic disease. SUMMARY: Sudden hearing loss is an otologic emergency. Appropriate counseling of patients is necessary to allow physician and patient to make a joint, educated decision. It is paramount to rule out retrocochlear disorder and to follow patients closely for improvement or need for future auditory rehabilitation. PMID- 27379549 TI - Current state of stem cell-mediated therapies for facial nerve injury. AB - PURPOSE OF REVIEW: Interest in the application of stem cell therapy to nerve injury has grown exponentially in recent years, as the armamentarium of potential stem cell sources has increased. This article reviews literature on the recent developments in the application of stem cell therapy for facial nerve injury. RECENT FINDINGS: Current stem cell therapy for the treatment of peripheral nerve injury can be generalized into those that either enhance native neural regeneration via an anti-inflammatory effect or growth factor secretion, replace Schwann cells, or replace motor neurons. Animal studies have shown that nerve conduits seeded with stem cells (either undifferentiated or differentiated into Schwann-like cells) in sciatic and facial nerve injury models can promote nerve regeneration with similar efficacy to autologous nerve autografts. In-vivo studies have also shown that induced pluripotent stem cell-derived motor neurons, when transplanted into transected mouse tibial nerves, can form functional neuromuscular junctions with the denervated mouse triceps surae. SUMMARY: The authors believe that induced pluripotent stem cells have significant therapeutic potential. This source of human stem cells can be harvested with little morbidity, is isogenic to the donor, and has fewer ethical concerns compared with embryonic cellular sources. Further research is required to determine stem cell efficacy and safety. Questions of stem cell fate unpredictability and possible tumorigenesis must be addressed prior to human trials. PMID- 27379550 TI - Positively Charged Surface-Modified Solid Lipid Nanoparticles Promote the Intestinal Transport of Docetaxel through Multifunctional Mechanisms in Rats. AB - Solid lipid nanoparticles (SLNs) are one of the most promising nanocarriers to increase the oral absorption of drugs with poor solubility and low permeability. However, the absorption mechanism of SLNs remains incomplete and thus requires further careful consideration. In this study, positively charged chitosan (CS) modified SLNs or hydroxypropyl trimethylammonium chloride chitosan (HACC) modified SLNs were designed and their absorption mechanisms were fully clarified to improve the oral absorption of docetaxel (DTX). The HACC-DTX-SLNs showed the highest cellular uptake in Caco-2 cell monolayer; the transport efficacy in the follicle-associated epithelium cell monolayer was higher than that in the Caco-2 cell monolayer. The CS- or HACC-modified SLNs could reversibly regulate the transepithelial electrical resistance and the expressions of tight junction (TJ) associated proteins, such as claudin-1, occludin, and zonula occludens-1. The uptake of HACC-DTX-SLNs through Peyer's patches was higher than that of the normal tissue of the small intestine in rats. The enhanced absorption mechanisms of HACC-DTX-SLNs were mainly related to the caveola-mediated endocytosis, M cell phagocytosis, and reversible TJ opening. PMID- 27379551 TI - Unique CD8+ T Cell-Mediated Immune Responses Primed in the Liver. AB - BACKGROUND: The liver immune environment is tightly regulated to balance immune activation with immune tolerance. Understanding the dominant immune pathways initiated in the liver is important because the liver is a site for cell transplantation, such as for islet and hepatocyte transplantation. The purpose of this study is to examine the consequences of alloimmune stimulation when allogeneic cells are transplanted to the liver in comparison to a different immune locale, such as the kidney. METHODS: We investigated cellular and humoral immune responses when allogeneic hepatocytes are transplanted directly to the recipient liver by intraportal injection. A heterotopic kidney engraftment site was used for comparison to immune activation in the liver microenvironment. RESULTS: Transplantation of allogeneic hepatocytes delivered directly to the liver, via recipient portal circulation, stimulated long-term, high magnitude CD8 T cell-mediated allocytotoxicity. CD8 T cells initiated significant in vivo allocytotoxicity as well as rapid rejection of hepatocytes transplanted to the liver even in the absence of secondary lymph nodes or CD4 T cells. In contrast, in the absence of recipient peripheral lymphoid tissue and CD4 T cells, CD8 mediated in vivo allocytotoxicity was abrogated, and rejection was delayed when hepatocellular allografts were transplanted to the kidney subcapsular site. CONCLUSIONS: These results highlight the CD8-dominant proinflammatory immune responses unique to the liver microenvironment. Allogeneic cells transplanted directly to the liver do not enjoy immune privilege but rather require immunosuppression to prevent rejection by a robust and persistent CD8-dependent allocytotoxicity primed in the liver. PMID- 27379552 TI - Peripheral Vascular Disease and Death in Southern European Kidney Transplant Candidates: A Competing Risk Modeling Approach. AB - BACKGROUND: The association between peripheral vascular disease (PVD) and survival among kidney transplant (KT) candidates is uncertain. METHODS: We assessed 3851 adult KT candidates from the Andalusian Registry between 1984 and 2012. Whereas 1975 patients received a KT and were censored, 1876 were on the waiting list at any time. Overall median waitlist time was 21.2 months (interquartile range, 11-37.4). We assessed the association between PVD and mortality in waitlisted patients using a multivariate Cox regression model, with a competing risk approach as a sensitivity analysis. RESULTS: Peripheral vascular disease existed in 308 KT candidates at waitlist entry. The prevalence of PVD among nondiabetic and diabetic patients was 4.5% and 25.3% (P < 0.0001). All cause mortality was higher in candidates with PVD (45% vs 21%; P < 0.0001). Among patients on the waiting list (n = 1876) who died (n = 446; 24%), 272 (61%) died within 2 years after listing. Cumulative incidence of all-cause mortality at 2 years in patients with and without PVD was 23% and 6.4%, respectively (P < 0.0001); similar differences were observed in patients with and without diabetes. By competing risk models, PVD was associated with a 1.9-fold increased risk of mortality (95% confidence interval [95% CI], 1.4-2.5). This association was stronger in waitlisted patients without cardiac disease (subhazard ratio, 2.2; 95% CI, 1.6-3.1) versus those with cardiac disorders (subhazard ratio, 1.5; 95% CI, 0.9-2.5). No other significant interactions were observed. Similar results were seen after excluding diabetics. CONCLUSIONS: Peripheral vascular disease is a strong predictor of mortality in KT candidates. Identification of PVD at list entry may contribute to optimize targeted therapeutic interventions and help prioritize high-risk KT candidates. PMID- 27379553 TI - Eliminating Xenoantigen Expression on Swine RBC. AB - BACKGROUND: The rapidly improving tools of genetic engineering may make it possible to overcome the humoral immune barrier that prevents xenotransplantation. We hypothesize that levels of human antibody binding to donor tissues from swine must approximate the antibody binding occurring in allotransplantation. It is uncertain if this is an attainable goal. Here we perform an initial analysis of this issue by comparing human antibody binding to red blood cells (RBC) isolated from knockout swine and to allogeneic or autologous human RBC. METHODS: Human sera were incubated with RBC isolated from various genetically engineered swine or from humans. The level of IgG and IgM binding to these cells were compared using either flow cytometry or a novel mass spectrometric assay. RESULTS: Mass spectroscopic quantitation of human antibody binding demonstrated that as few as 3 gene inactivations can reduce the levels human antibody binding to swine RBC that is as low as autologous human RBC. Flow cytometry showed that RBC from 2-gene knockout swine exhibited less human antibody binding than human blood group O allogeneic RBC in 22% of tested sera. Deletion of a third gene from pigs resulted in 30% of human samples having less IgG and IgM RBC xenoreactivity than alloreactivity. CONCLUSIONS: Xenoantigenicity of swine RBC can be eliminated via gene disruption. These results suggest that the gene knockout approach may be able reduce antigenicity in other pig tissues to levels that enable the xenotransplantation humoral barrier to be overcome. PMID- 27379554 TI - The Epidemiology and Clinical Features of Clostridium difficile Infection in Liver Transplant Recipients. AB - BACKGROUND: Clostridium difficile infection (CDI) is common after liver transplantation (LT); however, few studies have examined the risk factors, clinical manifestations, and outcomes of CDI in this population. METHODS: A retrospective study of adults who underwent LT between January 1, 2011, and April 4, 2013, at The Mount Sinai Hospital was conducted. Potential risk factors were evaluated via univariate and multivariable analysis to determine predictors of CDI in this population. The clinical manifestations of CDI and patient outcomes were also reviewed. RESULTS: Clostridium difficile infection occurred in 27 (14%) of 192 patients after LT. In multivariable analysis, CDI was associated with having a model for end-stage liver disease score of 20 or greater (hazards ratio, 2.90; 95% confidence interval, 1.29-6.52; P = 0.010), and receiving a LT from a living donor (hazards ratio, 3.77; 95% confidence interval, 1.47-9.67; P = 0.006). Forty-one percent of CDI cases occurred within 1 week of LT. Seven percent of patients with CDI had a serum white blood cell count greater than 12 000 cells per MUL, and 26% had a temperature greater than 38.0 degrees C. After treatment 6 (22%) patients developed CDI relapse, and all were successfully treated. No patients died of CDI after a mean follow-up time of 1.8 years; however, overall survival was significantly lower among those with CDI (78% vs 92%; P = 0.033). CONCLUSIONS: Clostridium difficile infection after LT was associated with higher model for end-stage liver disease scores and receiving a LT from a living donor. Clostridium difficile infection often occurred soon after LT and was infrequently associated with leukocytosis or fever. Clostridium difficile infection in LT recipients was associated with lower overall survival. PMID- 27379555 TI - Cost-Effectiveness of Antibody-Based Induction Therapy in Deceased Donor Kidney Transplantation in the United States. AB - BACKGROUND: Induction therapy in deceased donor kidney transplantation is costly, with wide discrepancy in utilization and a limited evidence base, particularly regarding cost-effectiveness. METHODS: We linked the United States Renal Data System data set to Medicare claims to estimate cumulative costs, graft survival, and incremental cost-effectiveness ratio (ICER - cost per additional year of graft survival) within 3 years of transplantation in 19 450 deceased donor kidney transplantation recipients with Medicare as primary payer from 2000 to 2008. We divided the study cohort into high-risk (age > 60 years, panel-reactive antibody > 20%, African American race, Kidney Donor Profile Index > 50%, cold ischemia time > 24 hours) and low-risk (not having any risk factors, comprising approximately 15% of the cohort). After the elimination of dominated options, we estimated expected ICER among induction categories: no-induction, alemtuzumab, rabbit antithymocyte globulin (r-ATG), and interleukin-2 receptor-antagonist. RESULTS: No-induction was the least effective and most costly option in both risk groups. Depletional antibodies (r-ATG and alemtuzumab) were more cost-effective across all willingness-to-pay thresholds in the low-risk group. For the high-risk group and its subcategories, the ICER was very sensitive to the graft survival; overall both depletional antibodies were more cost-effective, mainly for higher willingness to pay threshold (US $100 000 and US $150 000). Rabbit ATG appears to achieve excellent cost-effectiveness acceptability curves (80% of the recipients) in both risk groups at US $50 000 threshold (except age > 60 years). In addition, only r-ATG was associated with graft survival benefit over no-induction category (hazard ratio, 0.91; 95% confidence interval, 0.84-0.99) in a multivariable Cox regression analysis. CONCLUSIONS: Antibody-based induction appears to offer substantial advantages in both cost and outcome compared with no-induction. Overall, depletional induction (preferably r-ATG) appears to offer the greatest benefits. PMID- 27379556 TI - Decreased Circulating Sclerostin Levels in Renal Transplant Recipients With Persistent Hyperparathyroidism. AB - BACKGROUND: Sclerostin is an osteocyte-secreted soluble antagonist of the Wnt/beta-catenin signaling pathway requisite for osteoblast development and activity. The regulation of sclerostin expression in bone is complex. Parathyroid hormone (PTH) is recognized to be an important suppressor. Circulating sclerostin levels are 2- to 4-fold higher in patients with end-stage renal disease as compared with individuals with normal renal function. METHODS: We performed a longitudinal observational cohort study and case-control study in 50 de novo renal transplant recipients, 50 chronic kidney disease (CKD) patients (n = 50) matched for age, sex, and estimated glomerular filtration rate, and 23 renal transplant recipients referred for parathyroidectomy to define the impact of renal transplantation on circulating sclerostin levels and to clarify the role of persistent (tertiary) hyperparathyroidism. RESULTS: Sclerostin serum levels decreased by 61.2% (median) during the first 3 months after transplantation (1.24 vs 0.44 ng/mL, P < 0.0001) to increase thereafter toward levels observed in CKD counterparts (0.63 ng/ml). High PTH levels independently associated with low sclerostin levels, both at time of transplantation and at 1 year. Sclerostin levels significantly increased after parathyroidectomy (0.49 vs. 0.32 ng/ml, P < 0.0001). The time course of bone biomarkers after parathyroidectomy suggests that bone resorption normalizes earlier than bone formation. CONCLUSIONS: Circulating sclerostin levels appear to show a biphasic pattern after renal transplantation with a rapid and profound decrease, followed by gradual increase towards levels observed in CKD counterparts. Our data support the notion that PTH is an important regulator of circulating sclerostin levels. PMID- 27379557 TI - Center Volume Is Associated With Outcome After Pancreas Transplantation Within the Eurotransplant Region. AB - BACKGROUND: Outcome after surgery depends on several factors, among these, the annual volume-outcome relationship. This might also be the case in a highly complex field as pancreas transplantation. No study has investigated this relationship in a European setting. METHODS: All consecutive pancreas transplantations from January 2008 until December 2013 were included. Donor-, recipient-, and transplant-related factors were analyzed for their association with patient and graft survivals. Centers were classified in equally sized groups as being low volume (<5 transplantations on average each year in the 5 preceding years), medium volume (5-13/year), or high volume (>=13/year). RESULTS: In the study period, 1276 pancreas transplantations were included. Unadjusted 1-year patient survival was associated with center volume and was best in high volume centers, compared with medium and low volume: 96.5%, 94% and 92.3%, respectively (P = 0.017). Pancreas donor risk index (PDRI) was highest in high volume centers: 1.38 versus 1.21 in medium and 1.25 in low volume centers (P < 0.001). Pancreas graft survival at 1 year did not differ significantly between volume categories: 86%, 83.2%, and 81.6%, respectively (P = 0.114). After multivariate Cox regression analysis, higher PDRI (hazard ratio [HR], 1.60; P < 0.001), retransplantation (HR, 1.91; P = 0.002), and higher recipient body mass index (HR, 1.04; P = 0.024) were risk factors for pancreas graft failure. High center volume was protective for graft failure (HR, 0.70; P = 0.037) compared with low center volume. CONCLUSION: Patient and graft survival after pancreas transplantation are superior in higher volume centers. High volume centers have good results, even though they transplant organs with the highest PDRI. PMID- 27379558 TI - Regulatory Myeloid Cells for Tolerance-inducing Therapy: Finding Their Own Identity. PMID- 27379559 TI - Targeting Ischemia Reperfusion in Intestinal Transplantation by COX-2 Inhibition A S.M.A.R.T Approach? PMID- 27379560 TI - 32 Doses of Bortezomib for Desensitization Is Not Well Tolerated and Is Associated With Only Modest Reductions in Anti-HLA Antibody. AB - BACKGROUND: We previously showed that bortezomib (BTZ) partially depletes plasma cells, yet has limited efficacy for desensitization in kidney transplant candidates when up to 16 doses is given. METHODS: This study aimed to determine the safety and efficacy of 32 doses of BTZ (1.3 mg/m of body surface area) in 10 highly sensitized kidney transplant candidates with alloantibodies against their intended living donor. RESULTS: Dose reduction was needed in 2 patients and 2 others completely discontinued therapy for adverse events. Anti-HLA antibodies mean fluorescence intensity (MFI) values were stable prior to BTZ (P = 0.96) but decreased after therapy (mean decrease of 1916 [SE, 425] MFI, P < 0.01). No patient developed a negative crossmatch against their original intended donor, and the calculated panel-reactive antibodies based on MFI of 2000, 4000, and 8000 was unchanged in all patients. CONCLUSIONS: These data suggest that 32 doses of BTZ monotherapy was not well tolerated and resulted in only a modest reduction in anti-HLA antibodies. PMID- 27379561 TI - Effects of Spatially Dependent Mobilities on the Kinetics of the Diffusion Controlled Association Derived from the First-Passage-Time Approach. AB - Brownian dynamics (BD) simulations and the first-passage-time approach are applied to investigate diffusion-controlled association in a biologically relevant model system consisting of a fixed receptor with an elongated cavity and a capsule-like ligand that fits this cavity precisely. Before the binding at the receptor cavity, the ligand undergoes translational and rotational diffusion, either free or under the influence of electrostatic interactions with the receptor. The spatial dependence of the translational and rotational mobilities of the ligand resulting from its hydrodynamic interactions (HIs) with the receptor is accounted for in BD simulations, and an accurate numerical approach is applied for the evaluation of the spatially dependent mobility tensor of the ligand. Different magnitudes of electrostatic interactions (either attraction or repulsion) between the ligand and receptor are considered. The effective range of receptor-ligand electrostatic interactions is varied to account for their screening under different conditions of ionic strength. The effects of HIs on the kinetics of the diffusion-controlled association, evaluated for different electrostatic properties of binding partners, are thoroughly analyzed and discussed. PMID- 27379562 TI - Evaluation of lower blepharoplasty treated with the SmartLipo 1064-nm system and its clinical implications: A retrospective review. AB - INTRODUCTION: This study used the SmartLipo 1064-nm system to remove herniated orbital fat tissue to improve lower eyelid appearance. A retrospective review of 128 patients was performed to evaluate the size of prominent fat pads and complications. MATERIALS AND METHODS: Altogether, 128 patients underwent a procedure using the SmartLipo 1064-nm system via postseptal access, which helped locate fat tissue more precisely. Digital photographs were taken preoperatively and at one week and six months postoperatively. Eyebag sizes were determined preoperatively and six months postoperatively using the Non-Contact 3D Digitizer. RESULTS: Altogether, 118 primary and 10 revision patients (average age 31 years) were placed in one of two groups: mildly protruding fat pads (group 1, 86 patients) and moderately protruding fat pads (group 2, 42 patients). After injection of about 1 ml of anesthetic and 1 ml of 0.9% iced saline on each side, the patients received an average 450 joules of energy delivered at 20 Hz and 3 W. Postoperatively, the eyebag's height, depth, and area were significantly reduced in both groups (r = 0.000). The main symptoms (swelling, chemosis, engorgement, and pain) subsided within 5-7 days. CONCLUSION: The SmartLipo 1064-nm system with postseptal access, a minimally invasive procedure, can be used to correct mildly and moderately prominent fat pads. PMID- 27379563 TI - Frontostriatal Connectivity Changes in Major Depressive Disorder After Repetitive Transcranial Magnetic Stimulation: A Randomized Sham-Controlled Study. AB - OBJECTIVE: The aim of this randomized, sham-controlled study was to investigate the therapeutic effects of underlying neurobiological changes after 2-week repetitive transcranial magnetic stimulation (rTMS) treatment using functional connectivity magnetic resonance imaging in patients with major depression. METHODS: Twenty-four patients with major depressive disorder diagnosed with DSM IV-TR criteria were randomly assigned to the active rTMS (n = 13) or sham (n = 11) groups from January 2009 to June 2011. rTMS was given for 2 weeks at 110% of the motor threshold for 10 minutes at 10 Hz over the left dorsolateral prefrontal cortex (DLPFC). Resting state functional connectivity was evaluated before and after rTMS. The 17-item Hamilton Depression Rating Scale (HDRS) was administered, and neurocognitive tasks were performed. We examined between-group differences in functional connectivity changes from the bilateral DLPFC. RESULTS: Participants in the active rTMS group showed significant clinical improvement in HDRS scores compared to those in the sham group (P < .001). After 2-week rTMS, there were significant differences in changes in DLPFC-left caudate connectivity (corrected P < .05): the active group showed a greater reduction of connectivity strength between the DLPFC and left caudate compared to the sham group. Reduced levels of DLPFC-left caudate connectivity predicted improvement in depressive symptoms (r = 0.58, P = .001). Additionally, a positive correlation between residual depressive symptoms and connectivity strength after 2-week rTMS was found (r = 0.46, P = .023). CONCLUSIONS: High-frequency rTMS over the left DLPFC showed therapeutic effects in patients with major depression. The therapeutic effect of rTMS is related to the modulation of functional connectivity in the frontostriatal network. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01325831. PMID- 27379564 TI - HLA: revisiting an old suspect in the complex pathogenesis of posttransplant lymphoproliferative disorders. PMID- 27379565 TI - Quality of Life is Similar between Long-term Survivors of Indolent and Aggressive Non-Hodgkin Lymphoma. AB - Differences in quality of life (QOL) of long-term survivors of aggressive or indolent subtypes of non-Hodgkin lymphoma (NHL) have not been frequently evaluated. We assessed these differences by analyzing results of a large QOL survey of long-term NHL survivors. We hypothesized that the incurable nature of indolent NHL would relate to worse QOL in long-term survivors while the potentially cured long-term survivors of aggressive lymphoma would have better QOL. We found that QOL was similar between the two groups. Results suggest that patients with indolent NHL are coping well with their disease, yet experience some overall feelings of life threat. PMID- 27379566 TI - Expression of Apoptotic and Antioxidant Enzyme Genes in Sheep Oocytes and In Vitro Produced Embryos. AB - The present study was to find out the expression pattern and relative expression level of apoptotic (Bcl2, Bax, Casp3, and PCNA) and antioxidant enzyme [(GPx, Cu/Zn-SOD (SOD1) and Mn-SOD (SOD2)] genes in sheep oocytes and developing embryos produced in vitro by conventional RT-PCR and real time qPCR, respectively. Different developmental stages of embryos were produced in vitro from oocytes collected from local slaughter house ovaries. RT-PCR amplicons showed expression of Bcl2 and PCNA in all stages except at morula. In contrast Bax and Casp3 were expressed in all stages. GPx and SOD1 were expressed in all stages but SOD2 was not expressed in 8-16 cells, although expressed in the remaining stages. The qPCR analysis reflected that Bcl2 expression was significantly (P < 0.05) downregulated in morula and maximum upregulated expression was observed in in vitro matured oocytes. Higher upregulated expression (P < 0.05) of Bax was in morula and downregulated expression was at 2-4 cells. Casp3 was significantly upregulated at 8-16 cells and downregulated in in vitro matured oocyte. PCNA expression was highest at blastocyst and least expression was at morula. GPx was expressed significantly highest in matured oocytes and least expression was at zygote. SOD1 was expressed significantly highest at 8-16 cells and least expression was at zygote. Expression of SOD2 was least among all the antioxidant enzymes but significantly higher expression of SOD2 was in immature oocyte; however, least expression was at 8-16 cells. It can be concluded from the study that the sheep embryos produced in vitro are highly sensitive to culture condition, which alters the expression level of apoptotic and antioxidant enzyme genes. PMID- 27379567 TI - Mycophenolate Mofetil for the Treatment of Multiple Sclerosis-associated Uveitis. AB - PURPOSE: To report the efficacy of mycophenolate mofetil (MMF) as adjunctive therapy for the treatment of multiple sclerosis (MS)-associated uveitis. METHODS: In this retrospective, interventional case series, patients with MS-associated uveitis who were treated by MMF as an adjunct therapy to systemic corticosteroid were studied. Patients' demographics, clinical course, response to treatment, and complications were assessed. RESULTS: A total of 30 eyes of 15 patients with a mean age of 34.5 +/- 8.3 years were studied. In three patients (20%), onset of uveitis preceded the diagnosis of MS. The course of MS was relapsing-remitting in 11 patients (73.3%) and secondary progressive in four patients (26.7%). At 1 year after institution of MMF, all the patients were on oral prednisolone <= 7.5 mg/day, all eyes were quiet without macular edema, and 53.3% of eyes gained visual improvement. Supplemental periocular and intraocular injections were needed during the first 6 months after starting MMF therapy. The systemic adverse effects were transient and minor in severity. CONCLUSIONS: MMF had beneficial effects on vision and intraocular inflammation with an acceptable safety profile. PMID- 27379568 TI - Associations of MicroRNA Polymorphisms (miR-146a, miR-196a2, and miR-499) with the Risk of Hypertension in the Korean Population. AB - AIMS: Polymorphisms in microRNA (miR) genes are thought to be associated with various cancers and vascular diseases. To date, however, the effects of the miR gene polymorphisms on susceptibility to hypertension have rarely been investigated. In this study, we investigated the associations of three miR gene polymorphisms (miR-146aC>G/rs2910164, miR-196a2T>C/rs11614913, and miR 499A>G/rs3746444) with the risk of hypertension in Korean patients. METHODS: A total of 855 study subjects (340 patients with hypertension and 515 healthy normotensive subjects) were included in this study. Genotyping of the three miR gene polymorphisms was accomplished by polymerase chain reaction-restriction fragment length polymorphism analyses. RESULTS: Significant differences were observed in the genotype distributions of the miR-146aC>G polymorphism between the hypertensive patients and controls with the GG genotype, in both model independent analyses, as well as in dominant (CC vs. CG+GG) and recessive (CC+CG vs. GG) models, being highly significantly associated with disease (AOR = 2.293, 95% CI: 1.466-3.586, p = 0.001; AOR = 1.727, 95% CI: 1.182-2.522, p = 0.015; AOR = 1.782, 95% CI: 1.267-2.506, p = 0.001, respectively). Neither the miR-196a2T>C nor the miR-499A>G polymorphisms were distributed significantly differently between hypertensive patients and control subjects. Several allelic combinations of the three miR polymorphisms were also associated with susceptibility to hypertension. Stratified analysis revealed that the miR-146aC>G and miR-499A>G polymorphisms are associated with a greater risk of hypertension. CONCLUSION: This study suggests that the variant of miR-146aC>G polymorphism and allelic combinations, at least in Koreans, affect susceptibility to hypertension. PMID- 27379569 TI - Central Body Fat Mass Measured by Bioelectrical Impedanciometry But Not Body Mass Index Is a High-Grade Prostate Cancer Risk Factor. AB - OBJECTIVE: To evaluate the association between body fat mass distribution measured by bioelectrical impedanciometry (BEI) and high-grade prostate cancer (HGPC). METHODS: We prospectively analyze 323 patients who underwent prostate biopsy. BEI was performed prior to biopsy. Prostate cancer (PC) was stratified according to D'Amico classification. For univariate analysis, Student t test was done. For multivariate analysis, bivariate logistic regression was performed using PSA, body mass index (BMI), percentage central body fat, percentage total body fat, and visceral fat as explicative variables for the diagnosis of HGPC. RESULTS: PC was found in 134 patients. Thirty seven (27.2%) were HGPC. This group had higher age, PSA, and percentage central body fat (p = 0.001, p = 0.001, p = 0.04). BMI showed no association with HRPC. Age, PSA, and percentage central body fat (OR 1,123, 95% CI 1,022-1,233, p = 0.001) were independent risk factors. CONCLUSIONS: Central body fat measured by BEI could explain the association between obesity and HGPC better than BMI suggesting the use of this technique to study body fat distribution. PMID- 27379571 TI - Radiological predictors of malignant transformation of IPMNs: importance of the predictive model validation. PMID- 27379570 TI - The Topography of Cortical Microinfarcts in Neurodegenerative Diseases and in Vascular Dementia: A Postmortem 7.0-Tesla Magnetic Resonance Imaging Study. AB - BACKGROUND: Cortical microinfarcts (CoMIs) are considered as barely visible lesions in clinical-neuroradiological correlation studies. On postmortem 7.0 tesla MRI, however, CoMIs of different size are easily detected. SUMMARY: The present MRI study investigates 84 postmortem brains with different neurodegenerative diseases and vascular dementia (VaD) for their topographic distribution and the prevalence of CoMIs. The mean numbers of CoMIs were determined on 6 hemispheric coronal sections and in 22 different gyri with a 7.0 tesla MRI Bruker BioSpin SA. A large coronal section at the level of the mammillary body was also used for neuropathological evaluation. CoMIs were predominantly observed in the prefrontal and postcentral sections of VaD brains. The mean number of CoMIs was significantly increased in the inferior frontal and in the cingulate gyri of VaD brains compared to the controls. No topographic differences were observed in the neurodegenerative diseases. KEY MESSAGES: As the inferior frontal and the cingulated gyri are areas frequently involved in VaD, CoMIs in those strategic locations must have an impact on the evolution of the vascular cognitive decline in those patients. PMID- 27379572 TI - NeurHistAlert 22. PMID- 27379573 TI - Construction of Functional Monomeric Type 2 Isopentenyl Diphosphate:Dimethylallyl Diphosphate Isomerase. AB - Type 2 isopentenyl diphosphate:dimethylallyl diphosphate isomerase (IDI-2) catalyzes the interconversion of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) in the isoprenoid biosynthetic pathway. The enzyme from Streptomyces pneumoniae (spIDI-2) is a homotetramer in solution with behavior, including a substantial increase in the rate of FMN reduction by NADPH in the presence of IPP, suggesting that substrate binding at one subunit alters the kinetic and binding properties of another. We now report the construction of catalytically active monomeric spIDI-2. The monomeric enzyme contains a single point mutation (N37A) and a six-residue C-terminal deletion that preserves the secondary structure of the subunits in the wild-type (wt) homotetramer. UV-vis spectra of the enzyme-bound flavin mononucleotide (FMN) cofactor in FMNox, FMNred, and FMNred.IPP/DMAPP states are the same for monomeric and wt homotetrameric spIDI-2. The mutations in monomeric IDI-2 lower the melting temperature of the protein by 20 degrees C and reduce the binding affinities of FMN and IDI by 40-fold but have a minimal effect on kcat. Stopped-flow kinetic studies of monomeric spIDI-2 showed that the rate of reduction of FMN by NADH (k = 1.64 * 10(-3) s(-1)) is substantially faster when IPP is added to the monomeric enzyme (k = 0.57 s(-1)), similar to behavior seen for wt-spIDI-2. Our results indicate that cooperative interactions among subunits in the wt homotetramer are not responsible for the increased rate of reduction of spIDI-2.FMN by NADH, and two possible scenarios for the enhancement are suggested. PMID- 27379576 TI - [Not Available]. PMID- 27379575 TI - Cooperative inference: Features, objects, and collections. AB - Cooperation plays a central role in theories of development, learning, cultural evolution, and education. We argue that existing models of learning from cooperative informants have fundamental limitations that prevent them from explaining how cooperation benefits learning. First, existing models are shown to be computationally intractable, suggesting that they cannot apply to realistic learning problems. Second, existing models assume a priori agreement about which concepts are favored in learning, which leads to a conundrum: Learning fails without precise agreement on bias yet there is no single rational choice. We introduce cooperative inference, a novel framework for cooperation in concept learning, which resolves these limitations. Cooperative inference generalizes the notion of cooperation used in previous models from omission of labeled objects to the omission values of features, labels for objects, and labels for collections of objects. The result is an approach that is computationally tractable, does not require a priori agreement about biases, applies to both Boolean and first-order concepts, and begins to approximate the richness of real-world concept learning problems. We conclude by discussing relations to and implications for existing theories of cognition, cognitive development, and cultural evolution. (PsycINFO Database Record PMID- 27379574 TI - Association of Specific Dietary Fats With Total and Cause-Specific Mortality. AB - IMPORTANCE: Previous studies have shown distinct associations between specific dietary fat and cardiovascular disease. However, evidence on specific dietary fat and mortality remains limited and inconsistent. OBJECTIVE: To examine the associations of specific dietary fats with total and cause-specific mortality in 2 large ongoing cohort studies. DESIGN, SETTING, AND PARTICIPANTS: This cohort study investigated 83 349 women from the Nurses' Health Study (July 1, 1980, to June 30, 2012) and 42 884 men from the Health Professionals Follow-up Study (February 1, 1986, to January 31, 2012) who were free of cardiovascular disease, cancer, and types 1 and 2 diabetes at baseline. Dietary fat intake was assessed at baseline and updated every 2 to 4 years. Information on mortality was obtained from systematic searches of the vital records of states and the National Death Index, supplemented by reports from family members or postal authorities. Data were analyzed from September 18, 2014, to March 27, 2016. MAIN OUTCOMES AND MEASURES: Total and cause-specific mortality. RESULTS: During 3 439 954 person years of follow-up, 33 304 deaths were documented. After adjustment for known and suspected risk factors, dietary total fat compared with total carbohydrates was inversely associated with total mortality (hazard ratio [HR] comparing extreme quintiles, 0.84; 95% CI, 0.81-0.88; P < .001 for trend). The HRs of total mortality comparing extreme quintiles of specific dietary fats were 1.08 (95% CI, 1.03-1.14) for saturated fat, 0.81 (95% CI, 0.78-0.84) for polyunsaturated fatty acid (PUFA), 0.89 (95% CI, 0.84-0.94) for monounsaturated fatty acid (MUFA), and 1.13 (95% CI, 1.07-1.18) for trans-fat (P < .001 for trend for all). Replacing 5% of energy from saturated fats with equivalent energy from PUFA and MUFA was associated with estimated reductions in total mortality of 27% (HR, 0.73; 95% CI, 0.70-0.77) and 13% (HR, 0.87; 95% CI, 0.82-0.93), respectively. The HR for total mortality comparing extreme quintiles of omega-6 PUFA intake was 0.85 (95% CI, 0.81-0.89; P < .001 for trend). Intake of omega-6 PUFA, especially linoleic acid, was inversely associated with mortality owing to most major causes, whereas marine omega-3 PUFA intake was associated with a modestly lower total mortality (HR comparing extreme quintiles, 0.96; 95% CI, 0.93-1.00; P = .002 for trend). CONCLUSIONS AND RELEVANCE: Different types of dietary fats have divergent associations with total and cause-specific mortality. These findings support current dietary recommendations to replace saturated fat and trans-fat with unsaturated fats. PMID- 27379578 TI - Different Ipsi- and Contralateral Glial Responses to Anti-VEGF and Triamcinolone Intravitreal Injections in Rats. AB - PURPOSE: To investigate the glial response of the rat retina to single or repeated intravitreal injections (IVI). METHODS: Albino Sprague-Dawley rats received one or three (one every 7 days) IVI of anti-rat VEGF (5 MUL; 0.015 MUg/MUL), triamcinolone (2.5 or 5 MUL; 40 MUg/MUL; Trigon Depot), bevacizumab (5 MUL; 25 MUg/MUL; Avastin), or their vehicles (PBS and balanced salt solution) and were processed 7 days after the last injection. Retinas were dissected as whole mounts and incubated with antibodies against: Iba1 (Ionized Calcium-Binding Adapter Molecule 1) to label retinal microglia, GFAP (Glial Fibrillary Acidic Protein) to label macroglial cells, and vimentin to label Muller cells. The retinas were examined with fluorescence and confocal microscopy, and the numbers of microglial cells in the inner retinal layers were quantified using a semiautomatic method. RESULTS: All the injected substances caused an important micro- and macroglial response locally at the injection site and all throughout the injected retina that was exacerbated by repeated injections. The microglial response was also observed but was milder in the contralateral noninjected eyes. The IVI of the humanized antibody bevacizumab caused a very strong microglial reaction in the ipsilateral retina. Two types of macroglial response were observed: astrocyte hypertrophy and Muller end-foot hypertrophy. While astrocyte hypertrophy was widespread throughout the injected retina, Muller end-foot hypertrophy was localized and more extensive with triamcinolone use or after repeated injections. CONCLUSIONS: Intravitreal injections cause micro- and macroglial responses that vary depending on the injected agent but increase with repeated injections. This inflammatory glial response may influence the effects of the injected substances on the retina. PMID- 27379577 TI - Familial Clustering of Staphylococcus aureus Bacteremia in First-Degree Relatives: A Danish Nationwide Cohort Study. AB - BACKGROUND: A genetic predisposition to Staphylococcus aureus bacteremia has been demonstrated in animals, suggesting that genetic differences might influence susceptibility to S aureus in humans. OBJECTIVE: To determine whether a history of S aureus bacteremia in first-degree relatives increases the rate of the disease, and whether this rate is affected by the type of family relationship (that is, parent or sibling) or by how the relative acquired the infection. DESIGN: Register-based nationwide cohort study (1992 to 2011). SETTING: Denmark. PARTICIPANTS: First-degree relatives (children or siblings) of patients previously hospitalized with S aureus bacteremia. MEASUREMENTS: Poisson regression models were used to calculate standardized incidence ratios (SIRs) of S aureus bacteremia, with the incidence rate in the population as a reference. RESULTS: 34 774 individuals (the exposed cohort) with a first-degree relative (index case patient) previously hospitalized with S aureus bacteremia were followed up for a median of 7.8 years (interquartile range, 3.6 to 13.0). A higher rate of S aureus bacteremia was observed among these first-degree relatives (SIR, 2.49 [95% CI, 1.95 to 3.19]) than in the background population. The estimate was significantly higher if the index case patient was a sibling (SIR, 5.01 [CI, 3.30 to 7.62]) than a parent (SIR, 1.96 [CI, 1.45 to 2.67]; interaction P < 0.0001). No interaction was observed regarding the sex of the first-degree relative (interaction P for parents = 0.85; interaction P for siblings = 0.92). Stratifying by disease acquisition revealed the highest rates in individuals exposed to index case patients with non-hospital-acquired infection. Few were infected with genetically identical bacteremia isolates. LIMITATION: The rarity of the outcome limited the number of variables in the multiple regression analysis, and whether nonsignificant interactions were true or caused by insufficient statistical power remains uncertain. CONCLUSION: A significant familial clustering of S aureus bacteremia was found, with the greatest relative rate of disease observed in individuals exposed to siblings with a history of the disease. PRIMARY FUNDING SOURCE: The Danish Heart Foundation and the Christian Larsen and Judge Ellen Larsen Foundation. PMID- 27379579 TI - A Systematic Comparison of Static and Dynamic Cues for Depth Perception. AB - PURPOSE: A clinical diagnosis of stereoblindness does not necessarily preclude compelling depth perception. Qualitative observations suggest that this may be due to the dynamic nature of the stimuli. The purpose of this study was to systematically investigate the effectiveness of static and dynamic stereoscopic stimuli. METHODS: Stereoscopic stimuli were presented on a passive polarized stereoscopic monitor and were manipulated as follows: static disparity (baseline condition), dynamic disparity (change in z-location), change in stimulus pattern, change in z-location with pattern change, change in x-location (horizontal shift), a control (nil-disparity signal). All depth-detection thresholds were measured simultaneously using an adaptive four-alternative-forced-choice (4AFC) paradigm with all six conditions randomly interleaved. RESULTS: A total of 127 participants (85 women, 42 men; mean [SD] age, 21 [5] years) with visual acuity better than 0.22 logMAR in both eyes were assessed. In comparison to the static disparity condition, depth-detection thresholds were up to 50% lower for the dynamic disparity conditions, with and without pattern change (P < 0.001). The presence of a changing pattern in isolation (P = 0.71) or a horizontal shift (P = 0.41) did not affect the thresholds. CONCLUSIONS: Dynamic disparity information facilitates the extraction of depth in comparison to static disparity signals. This finding may account for the compelling perception of depth reported in individuals with no measurable static stereoacuity. Our findings challenge the traditional definition of stereoblindness and suggest that current diagnostic tests using static stimuli may be suboptimal. We argue that both static and dynamic stimuli should be employed to fully assess the binocular potential of patients when considering management options. PMID- 27379580 TI - Superposition Violations in the Compensatory Eye Movement System. AB - PURPOSE: Compensatory eye movements (CEM) maintain a stable image on the retina by minimizing retinal slip. The optokinetic reflex (OKR) and vestibulo-ocular reflex (VOR) compensate for low and high velocity stimuli, respectively. The OKR system is known to be highly nonlinear. The VOR is generally modeled as a linear system and assumed to satisfy the superposition and homogeneity principles. To probe CEM violation of the superposition principle, we recorded eye movement responses in C57BL/6 mice to sum of sine (SoS) stimulation, a combination of multiple nonharmonic inputs. METHODS: We tested the VOR, OKR, VVOR (visually enhanced VOR), and SVOR (suppressed VOR). We used stimuli containing 0.6 Hz, 0.8 Hz, 1.0 Hz, and 1.9 Hz. Power spectra of SoS stimuli did not yield distortion products. Gains and delays of SoS and single sine (SS) responses were compared to yield relative gains and delays. RESULTS: We find the superposition principle is violated primarily in the OKR, VOR, and SVOR conditions. In OKR, we observed relative gain suppression of the lower SoS stimulus frequency component irrespective of the absolute frequency. Conversely, SVOR and VOR results showed gain enhancement of the lower frequency component and overall decrease in lead. Visually enhanced VOR results showed trends for overall gain suppression and delay decrease. CONCLUSIONS: Compensatory eye movements arguably depend on predictive signals. These results may reflect better prediction for SS stimuli. Natural CEM system stimulation generally involves complex frequency spectra. Use of SoS stimuli is a step toward unravelling the signals that really drive CEM and the predictive algorithms they depend on. PMID- 27379584 TI - Incorrect Answer in CME Online Quiz Questions. PMID- 27379583 TI - Red Scaly Eruption in an Otherwise Healthy 2-Month-Old Boy. PMID- 27379585 TI - Donor Breast Milk. PMID- 27379588 TI - Letters to the Editor. PMID- 27379586 TI - In This Issue * July 15, 2016. PMID- 27379589 TI - What Is Your Diagnosis? PMID- 27379590 TI - ECG of the Month. PMID- 27379591 TI - Pathology in Practice. PMID- 27379592 TI - Pathology in Practice. PMID- 27379593 TI - The Association of Shelter Veterinarians' 2016 Veterinary Medical Care Guidelines for Spay-Neuter Programs. AB - As community efforts to reduce the overpopulation and euthanasia of unwanted and unowned cats and dogs have increased, many veterinarians have increasingly focused their clinical efforts on the provision of spay-neuter services. Because of the wide range of geographic and demographic needs, a wide variety of spay neuter programs have been developed to increase delivery of services to targeted populations of animals, including stationary and mobile clinics, MASH-style operations, shelter services, community cat programs, and services provided through private practitioners. In an effort to promote consistent, high-quality care across the broad range of these programs, the Association of Shelter Veterinarians convened a task force of veterinarians to develop veterinary medical care guidelines for spay-neuter programs. These guidelines consist of recommendations for general patient care and clinical procedures, preoperative care, anesthetic management, surgical procedures, postoperative care, and operations management. They were based on current principles of anesthesiology, critical care medicine, infection control, and surgical practice, as determined from published evidence and expert opinion. They represent acceptable practices that are attainable in spay-neuter programs regardless of location, facility, or type of program. The Association of Shelter Veterinarians envisions that these guidelines will be used by the profession to maintain consistent veterinary medical care in all settings where spay-neuter services are provided and to promote these services as a means of reducing sheltering and euthanasia of cats and dogs. PMID- 27379594 TI - Detection of heart rate and rhythm with a smartphone-based electrocardiograph versus a reference standard electrocardiograph in dogs and cats. AB - OBJECTIVE To evaluate the diagnostic utility of ECGs acquired with a smartphone based device, compared with reference 6-lead ECGs, for identification of heart rate and rhythm in dogs and cats. DESIGN Prospective study. ANIMALS 51 client owned dogs and 27 client-owned cats. PROCEDURES Patients examined by a small animal referral cardiology service between April 2012 and January 2013 were enrolled consecutively. In each patient, a 30-second ECG was simultaneously acquired with a smartphone-based device (a bipolar, single-lead recorder coupled to a smartphone with an ECG application) and a standard 6-lead ECG machine. Recordings were evaluated by 3 board-certified cardiologists, and intra- and interobserver agreement were evaluated for both rhythm diagnosis and QRS polarity identification. RESULTS Values for instantaneous and mean heart rates for the smartphone-acquired and reference ECGs were within 1 beat of each other when mean heart rates were calculated. Intraobserver agreement for rhythm assessment was very high, with maximum disagreement for any observer for only 2 of 51 dogs and only 4 of 27 cats. There was minimal disagreement in the polarity of depolarization between the smartphone-acquired and reference ECGs in dogs but frequent disagreement in cats. Interobserver agreement for smartphone-acquired ECGs was similar to that for reference ECGs. with all 3 observers agreeing on the rhythm analysis and minimal disagreement on polarity. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that ECGs acquired with the smartphone-based device accurately identified heart rate and rhythm in dogs and cats. Thus, the device may allow veterinarians to evaluate and manage cardiac arrhythmias relatively inexpensively at the cage side and could also allow clinicians to rapidly share information via email for further consultation, potentially enhancing patient care. PMID- 27379595 TI - Laryngeal structure and function in dogs with cough. AB - OBJECTIVE To investigate the prevalence and type of laryngeal abnormalities in dogs examined because of cough that did not have signs of upper airway disease and to compare the prevalence of those abnormalities among dogs with various respiratory tract diseases. DESIGN Prospective study. ANIMALS 138 dogs with cough that did not have signs of upper airway disease. PROCEDURES The study was conducted between July 2001 and October 2014 and included dogs examined for cough that had laryngoscopic and bronchoscopic examinations performed by 1 examiner. Laryngeal hyperemia and swelling were recorded, and laryngeal function was assessed before and after doxapram stimulation when indicated. Results were compared among dogs on the basis of cough duration (acute [< 2 weeks], subacute [2 weeks to 2 months], and chronic [> 2 months]) and disease diagnosed (inflammatory airway disease, airway collapse, lower respiratory tract infection, and eosinophilic bronchopneumopathy). RESULTS Laryngeal hyperemia was detected in 73 of 134 (54%) dogs with cough of subacute or chronic duration, and its prevalence did not vary significantly among dogs with various diseases. Thirteen dogs had laryngeal paresis, and 13 dogs had laryngeal paralysis; dysphonia (n = 2) and stridor (1) were uncommon findings in those dogs. The prevalence of laryngeal dysfunction (paresis or paralysis) did not differ significantly among diseases. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that 26 of 138 (19%) dogs examined because of cough alone had laryngeal dysfunction, which suggested that a complete laryngoscopic examination should be included in the diagnostic evaluation of dogs with cough. PMID- 27379596 TI - Efficacy of a single dose of trazodone hydrochloride given to cats prior to veterinary visits to reduce signs of transport- and examination-related anxiety. AB - OBJECTIVE To evaluate the efficacy of a single dose of trazodone for reducing anxiety in cats during transport to a veterinary hospital and facilitating handling during veterinary examination. DESIGN Double-blind, placebo-controlled, randomized crossover study. ANIMALS 10 healthy client-owned cats (2 to 12 years of age) with a history of anxiety during transport or veterinary examination. PROCEDURES Each cat was randomly assigned to first receive trazodone hydrochloride (50 mg) or a placebo PO. The assigned treatment was administered, and each cat was placed in a carrier and transported by car to a veterinary clinic, where it received a structured veterinary examination. Owners scored their cat's signs of anxiety before, during, and after transport and examination. The veterinarian also assessed signs of anxiety during examination. After a 1- to 3-week washout period, each cat received the opposite treatment and the protocol was repeated. RESULTS Compared with placebo, trazodone resulted in a significant improvement in the cats' signs of anxiety during transport. Veterinarian and owner scores for ease of handling during veterinary examination also improved with trazodone versus the placebo. No significant differences were identified between treatments in heart rate or other physiologic variables. The most common adverse event related to trazodone administration was signs of sleepiness. CONCLUSIONS AND CLINICAL RELEVANCE Oral administration of a single dose of trazodone to cats prior to a veterinary visit resulted in fewer signs of transport- and examination-related anxiety than did a placebo and was generally well tolerated by most cats. Use of trazodone in this manner may promote veterinary visits and, consequently, enhance cat welfare. PMID- 27379597 TI - Outcomes and complications following surgical correction of grade IV medial patellar luxation in dogs: 24 cases (2008-2014). AB - OBJECTIVE To determine short- and long-term outcomes and complications of dogs undergoing surgical correction of grade IV medial patellar luxation (MPL). DESIGN Retrospective case series. ANIMALS 24 dogs (29 stifle joints) that underwent surgical correction of grade IV MPL between March 2008 and April 2014. PROCEDURES Medical records of all dogs were reviewed. When available, long-term follow-up information was obtained for each dog via the orthopedic surgeon (results of orthopedic examination and radiographic interpretation) and the dog's owner (responses to a questionnaire regarding postsurgical outcomes). Types of postsurgical complications and intervals to follow-up data collection were recorded. Recurrence of MPL was recorded separately. Successful outcome was defined as one without catastrophic complication, with owner-reported full or acceptable return to function and a surgeon- and owner-assigned pain or lameness score < 3. RESULTS 24% (7/29) of stifle joints had major complications, and 21% (6) of joints required surgical revision. Grade II to IV recurrence of MPL was identified in 21% (6) of stifle joints. One dog had a catastrophic complication requiring limb amputation. For all other dogs, owner-reported return to function was full or acceptable. Surgeon-assigned pain and lameness scores for all dogs at the final follow-up evaluation were < 2/5 (0 = pain or lameness free). Surgical correction of grade IV MPL had an overall success rate of 93% (27/29). CONCLUSIONS AND CLINICAL RELEVANCE Surgical correction of grade IV MPL in dogs had a favorable overall success rate; however, owners should be counseled regarding the high rate of complications associated with surgery. PMID- 27379598 TI - Treatment of intrathoracic grass awn migration with video-assisted thoracic surgery in two dogs. AB - CASE DESCRIPTION A 17-month-old sexually intact male Vizsla and a 2-year-old spayed female mixed-breed dog were examined because of suspected intrathoracic grass awn migration. CLINICAL FINDINGS Thoracic CT revealed focal areas of pulmonary infiltration in the right caudal lung lobe in one dog and in the left caudal lung lobe in the other. In 1 patient, bronchoscopy revealed 2 grass awns in the bronchi. Results of thoracic radiography and bronchoscopy were unremarkable in the second patient; however, a grass awn was recovered from the tonsillar crypt during oropharyngeal examination. TREATMENT AND OUTCOME In both dogs, grass awns were successfully retrieved from the pleural cavity by means of video-assisted thoracic surgery during 1-lung ventilation. In one patient, a grass awn was recovered bronchoscopically from the left caudal lung lobe bronchus and another was visualized distally in an accessory lung lobe bronchus but could not be retrieved. This dog underwent accessory lung lobectomy. The second dog underwent left caudal lung lobectomy. Both patients recovered uneventfully from surgery, were discharged from the hospital, and had no apparent recurrence of clinical signs at telephone follow-up 31 months and 18 months after surgery. CLINICAL RELEVANCE With careful case selection, successful management of intrathoracic grass awn migration in dogs can be achieved by means of video assisted thoracic surgery. Comprehensive preoperative evaluation including both computed tomography and bronchoscopy is suggested. Further investigation is necessary to evaluate whether treatment of this condition with video-assisted thoracic surgery is as effective as with traditional open thoracotomy. PMID- 27379599 TI - Cardiomyopathy in a Harris hawk (Parabuteo unicinctus). AB - CASE DESCRIPTION An adult sexually intact female Harris hawk (Parabuteo unicinctus) housed at a wildlife hospital was evaluated because of acute collapse during an educational exhibition. CLINICAL FINDINGS Physical examination and hematologic analysis revealed no abnormalities; radiography revealed findings consistent with a previous tibiotarsal fracture. Coelioscopy with histologic examination and fungal culture of lung and air sac samples revealed anthracosis but no fungal infection. The hawk was discharged and temporarily removed from the education program; 1 month later, upon reintroduction into the program, it collapsed again. Physical examination and hematologic findings were similar to those after the first episode. Transcoelomic and transesophageal echocardiography and CT angiocardiography findings were consistent with cardiomyopathy. TREATMENT AND OUTCOME Initial cardiac treatment included furosemide (0.5 mg/kg [0.23 mg/lb], PO, q 24 h) and pimobendan (10 mg/kg [4.5 mg/lb], PO, q 12 h). After 10 days of treatment, peak and trough plasma concentrations of pimobendan were measured at 25, 196 and 715.97 ng/mL, respectively; the dosage was decreased to 0.25 mg/kg (0.11 mg/lb), PO, every 12 hours. No overt signs of toxicosis were detected. A sample was collected to reevaluate plasma pimobendan concentration after 30 days of treatment; results were not obtained prior to the patient's death but revealed a peak concentration of 16.8 ng/mL, with an undetectable trough concentration. The hawk was found dead 6 months after initial evaluation. Necropsy revealed cardiomegaly, but histologic examination did not reveal an inciting cause of cardiac dysfunction. CLINICAL RELEVANCE Cardiac disease in raptors may be underreported. Transcoelomic and transesophageal echocardiography and CT angiography provided useful information for the diagnosis of cardiac disease in the hawk of this report. PMID- 27379601 TI - Electron-Catalyzed Fluoroalkylation of Vinyl Azides. AB - The transition-metal free fluoroalkylation of vinyl azides is herein reported. This operationally simple reaction employs the Togni reagent as a CF3 source, Bu4 NI as an initiator, and occurs under electron catalysis. A range of readily prepared starting materials are functionalized using this approach to produce both phenanthridines and quinoxalin-2-ones. PMID- 27379602 TI - Intramolecular transformation of an antifungal antibiotic nystatin A1 into its isomer, iso-nystatin A1 - structural and molecular modeling studies. AB - Nystatin A1 , a polyene macrolide antifungal antibiotic, in a slightly basic or acidic solution undergoes an intramolecular transformation, yielding a structural isomer, the translactonization product, iso-nystatin A1 with lactone ring diminished by two carbon atoms. Structural evidence is provided by advanced NMR and Mass Spectrometry (MS) studies. Molecular dynamics simulations and quantum mechanics calculations gave the insight into the course and mechanism of the transformation and its effect on the conformation of the subject molecule. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27379603 TI - Group relationships in early and late sessions and improvement in interpersonal problems. AB - Groups are more effective when positive bonds are established and interpersonal conflicts resolved in early sessions and work is accomplished in later sessions. Previous research has provided mixed support for this group development model. We performed a test of this theoretical perspective using group members' (actors) and aggregated group members' (partners) perceptions of positive bonding, positive working, and negative group relationships measured early and late in interpersonal growth groups. Participants were 325 Italian graduate students randomly (within semester) assigned to 1 of 16 interpersonal growth groups. Groups met for 9 weeks with experienced psychologists using Yalom and Leszcz's (2005) interpersonal process model. Outcome was assessed pre- and posttreatment using the Inventory of Interpersonal Problems, and group relationships were measured at Sessions 3 and 6 using the Group Questionnaire. As hypothesized, early measures of positive bonding and late measures of positive working, for both actors and partners, were positively related to improved interpersonal problems. Also as hypothesized, late measures of positive bonding and early measures of positive working, for both actors and partners, were negatively related to improved interpersonal problems. We also found that early actor and partner positive bonding and negative relationships interacted to predict changes in interpersonal problems. The findings are consistent with group development theory and suggest that group therapists focus on group-as-a-whole positive bonding relationships in early group sessions and on group-as-a-whole positive working relationships in later group sessions. (PsycINFO Database Record PMID- 27379605 TI - Applying Physiologically Relevant Strains to Tenocytes in an In Vitro Cell Device Induces In Vivo Like Behaviors. AB - We have developed a novel cell stretching device (called Cell Gym) capable of applying physiologically relevant low magnitude strains to tenocytes on a collagen type I coated membrane. We validated our device thoroughly on two levels: (1) substrate strains, (2) cell level strains. Our cell level strain results showed that the applied stretches were transferred to cells accurately (~90%). Our gene expression data showed that mechanically stimulated tenocytes (4%) expressed a lower level of COL I gene. COX2 gene was increased but did not reach statistical significance. Our device was then tested to see if it could reproduce results from an in vivo study that measured time-dependent changes in collagen synthesis. Our results showed that collagen synthesis peaked at 24 hrs after exercise and then decreased, which matched the results from the in vivo study. Our study demonstrated that it is important to incorporate physiologically relevant low strain magnitudes in in vitro cell mechanical studies and the need to validate the device thoroughly to operate the device at small strains. This device will be used in designing novel tendon tissue engineering scaffolds in the future. PMID- 27379604 TI - Subsets of salivary duct carcinoma defined by morphologic evidence of pleomorphic adenoma, PLAG1 or HMGA2 rearrangements, and common genetic alterations. AB - BACKGROUND: The authors hypothesized that histogenetic classification of salivary duct carcinoma (SDC) could account for de novo tumors and those with morphologic or molecular evidence (pleomorphic adenoma gene 1 [PLAG1], high-mobility group AT hook 2 [HMGA2] rearrangement, amplification) of pleomorphic adenoma (PA). METHODS: SDCs (n = 66) were reviewed for morphologic evidence of PA. PLAG1 and HMGA2 alterations were detected by fluorescence in situ hybridization (FISH). PLAG1-positive tumors were tested by FISH for fibroblast growth factor receptor 1 (FGFR1) rearrangement. Thirty-nine tumors were analyzed using a commercial panel for mutations and copy number variations in 50 cancer-related genes. RESULTS: On the basis of combined morphologic and molecular evidence of PA, 4 subsets of SDC emerged: 1) carcinomas with morphologic evidence of PA but intact PLAG1 and HMGA2 (n = 22); 2) carcinomas with PLAG1 alteration (n = 18) or 3) HMGA2 alteration (n = 12); and 4) de novo carcinomas, without morphologic or molecular evidence of PA (n = 14). The median disease-free survival was 37 months (95% confidence interval, 28.4-45.6 months). Disease-free survival and other clinicopathologic parameters did not differ for the subsets defined above. Combined Harvey rat sarcoma viral oncogene homolog/phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit alpha (HRAS/PIK3CA) mutations were observed predominantly in de novo carcinomas (5 of 8 vs 2 of 31 tumors; P = .035). Erb-B2 receptor tyrosine kinase 2 (ERBB2) copy number gain was not observed in de novo carcinomas (0 of 8 vs 12 of 31 tumors; P = .08). Tumor protein 53 (TP53) mutations were more common in SDC ex pleomorphic adenomas than in de novo carcinomas (17 of 31 vs 1 of 8 tumors; P = .033). CONCLUSIONS: The genetic profile of SDC varies with the absence or presence of pre-existing PA and its cytogenetic signature. Most de novo SDCs harbor combined HRAS/PIK3CA mutations and no ERBB2 amplification. Cancer 2016;122:3136-44. (c) 2016 American Cancer Society. PMID- 27379606 TI - Determinants of knee replacement in subjects with a history of arthroscopy: data from the osteoarthritis initiative. AB - OBJECTIVE: To investigate the risk and determinants of knee replacement (KR) in subjects with or at risk of osteoarthritis (OA) and a history of arthroscopy. METHODS: Data from the osteoarthritis initiative cohort were analyzed (n = 4796, up to the seventh year of follow-up). Cox proportional hazard analysis was used to determine the risk of KR according to the history of arthroscopy. A multivariable model was used to determine the risk factors for KR among subjects with a history of arthroscopy (n = 842), including age, gender, body mass index, history of knee injury, and baseline physical activity scale for the elderly, Western Ontario and McMaster (WOMAC) total score, and radiographic Kellgren and Lawrence (KL) score. RESULTS: History of arthroscopy was associated with risk of KR after adjustments for the mentioned determinants of OA (HR: 1.90 (1.49-2.44); P value <0.001). Female gender (HR: 1.86 (1.30-2.68); P value <0.001), higher WOMAC (HR: 1.02 (1.01-1.03); P value <0.001), and KL score (HR: 2.64 (2.08-3.35); P value <0.001) increased the risk of KR among subjects with a history of arthroscopy. Subjects with a history of knee injury had 50 % lower risk of KR (HR: 0.50 (0.35-0.72); P value <0.001) after arthroscopy. CONCLUSION: Female gender, more clinical symptoms and radiographic signs of OA, was associated with higher risk of future KR in subjects with a history of arthroscopy. Subjects with arthroscopy in the setting of concomitant knee injury were 50 % less likely to undergo KR compared to subjects who underwent arthroscopy without a history of concomitant knee injury. PMID- 27379607 TI - Timing: the Achilles heel of forensic pathology. PMID- 27379608 TI - Sudden unexpected death due to severe pulmonary and cardiac sarcoidosis. AB - In this paper we report the autopsy findings of a 57 year old woman who died unexpectedly at home. She had been complaining of shortness of breath, episodes of dry coughing, and nausea. Her past medical and social history was unremarkable. She had no previous history of any viral or bacterial disease and no history of oncological disorders. Autopsy revealed multiple grayish-white nodular lesions in the pleura and epicardial fat and areas resembling fibrosis on the cut surface of the anterior and posterior wall of the left ventricle and interventricular septum. Histological examination of the lungs and heart revealed multiple well-formed noncaseating epithelioid cell granulomas with multinucleated giant cells. Death was attributed to myocardial ischemia due to vasculitis of intramural coronary artery branches associated with sarcoidosis. Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of noncaseating epithelioid cell granulomas in the affected organs and tissues. The diagnosis of sarcoidosis in this case was established when other causes of granulomatous disease such as tuberculosis, berylliosis, hypersensitivity pneumonitis, and giant cell myocarditis had been reasonably excluded. PMID- 27379609 TI - Anthropometric correlations between parts of the upper and lower limb: models for personal identification in a Sudanese population. AB - PURPOSE: Identification of a deceased individual is an essential component of medicolegal practice. However, personal identification based on commingled limbs or parts of limbs, necessary in investigations of mass disasters or some crimes, is a difficult task. Limb measurements have been utilized in the development of biological parameters for personal identification, but the possibility to estimate the dimensions of parts of limbs other than hands and feet has not been assessed. The present study proposes an approach to estimate the dimensions of various parts of limbs based on other limb measurements. METHODS: The study included 320 Sudanese adults, with equal representation of men and women. Nine limb dimensions were measured (five based on the upper limb, four based on the lower limb), and extensive statistical analysis of the distribution of values was performed. RESULTS: The results showed that all of the measured dimensions were sexually dimorphic and that there was a significant positive correlation between the dimensions of various parts of limbs. Regression models (direct and stepwise) were developed to estimate the dimensions of parts of limbs based on measurements pertaining to one or more other parts of limbs. CONCLUSIONS: The study revealed that the dimensions of parts of the upper and lower limb can be estimated from one another. These findings can be used in medicolegal practice and extended to constructive surgery, orthopedics, and prosthesis design for lost limbs. PMID- 27379610 TI - Fractional flow reserve-guided coronary angioplasty using paclitaxel-coated balloons without stent implantation: feasibility, safety and 6-month results by angiography and optical coherence tomography. AB - BACKGROUND: Percutaneous coronary interventions (PCI) with drug-coated balloons (DCB) might be a promising trade-off between balloon angioplasty and drug-eluting stents, since DCB inhibit neointimal proliferation and limit duration of dual antiplatelet therapy. We investigated the safety, feasibility, and 6-month results of fractional flow reserve (FFR)-guided use of the paclitaxel-coated SeQuent Please(r) balloon without stenting for elective PCI of de novo lesions. METHODS AND RESULTS: In 46 patients (54 lesions) with stable symptomatic coronary artery disease (CAD), a FFR-guided POBA (plain old balloon angioplasty) was performed. In case of a sufficient POBA result with residual stenosis < 40 %, FFR > 0.8 and no severe dissection, the target lesion was finally dilated using the DCB. Quantitative coronary angiography (QCA) was performed before and after the index procedure and at 6-month follow-up (f/u) to calculate late lumen loss (LLL) and net luminal gain (NLG). Optical coherence tomography (OCT) was performed at f/u to assess vascular remodeling. DCB-only treatment was applied to 43 patients (51 lesions), while 3 patients (3 lesions) needed provisional stenting. Invasive f/u was completed in 39 patients (47 lesions). At the stenotic site, the lumen diameter showed a trend toward progressive increase at f/u (LLL: -0.13 +/- 0.44 mm, n.s.; NLG: 1.10 +/- 0.53 mm, p < 0.001) without aneurysm formation or restenosis after DCB-only treatment. CONCLUSIONS: FFR-guided DCB-only PCI of de novo lesions appeared feasible and safe in stable CAD with clopidogrel discontinuation after 4 weeks, showing a trend toward positive vessel remodeling without lumen loss at 6 months. Clinical trial registration http://www.clinicaltrials.gov . Unique identifier: NCT02120859. PMID- 27379611 TI - BETAWIN-AHF study: effect of beta-blocker withdrawal during acute decompensation in patients with chronic heart failure. AB - OBJECTIVE: To evaluate the effects of discontinuing chronic beta-blocker (BB) treatment on short-term outcome in patients with chronic heart failure (CHF) during acute decompensation. METHODS: We selected all the patients previously diagnosed with CHF and currently on BB and attended for acute heart failure (AHF) in one of the 35 Spanish emergency departments participating in the EAHFE registry. Patients were classified according to BB maintenance or withdrawal (BBM or BBW, respectively) during the episode. In-hospital mortality was the primary endpoint; and 30-day mortality, 30-day combined endpoint, and prolonged hospitalization were secondary. We used logistic regression for adjustment of results according to the differences between the BBM and BBW groups, and stratified analysis by age, sex, left ventricular ejection fraction, chronic obstructive pulmonary disease, heart rate (HR), and BB type (carvedilol/bisoprolol) was performed. RESULTS: Among 2058 patients receiving chronic BB treatment, 1990 were analyzed: BBM 530 (27 %), BBW 1460 (73 %). Compared to BBM, BBW had a higher in-hospital mortality (5.5 vs 3.0 %; p < 0.05), 30-day mortality (8.7 vs 4.5 %; p < 0.01), and 30-day combined endpoint (29.8 vs 23.4 %; p < 0.05). Multivariate adjustment confirmed an independent direct association between BBW and in-hospital mortality (OR 1.89; 95 % CI 1.09-3.26) and 30-day mortality (OR 2.01; 95 % CI 1.28-3.15). Stratified analysis indicated no interaction by all the subgroups analyzed, except for HR (p = 0.01 for interaction), which showed a greater negative impact of BBW in patients with HR >80 bpm (OR 2.74; 95 % CI 1.13-6.63). CONCLUSIONS: In the absence of clear contraindications, BB treatment should be maintained during AHF episodes in patients already receiving BB at home. PMID- 27379612 TI - Risk factors for HIV positivity among more than 3,400 Tanzanian women. AB - In a cross-sectional study of 3,424 women from urban (Dar es Salaam) and rural (Pwani, Mwanza, and Mtwara) Tanzania, conducted in 2008-2009, we investigated risk factors for human immunodeficiency virus (HIV) and the association between different measures of human papillomavirus (HPV) and HIV positivity. Study participants were interviewed about socio-demographic and reproductive factors and sexual behavior. Blood samples were tested for HIV, and the women underwent a gynecological examination. HPV status was determined by Hybrid Capture 2, and HPV genotyping was performed using the LiPA Extra test. Multivariable logistic regression models estimating odds ratios (OR) and 95% confidence intervals (CI) were used. The overall HIV prevalence was 10.2%. HIV-positive women were more likely to have high-risk (HR) HPV detected (OR = 4.11; 95% CI: 3.23-5.24) and clinically visible genital warts (OR = 4.37; 95% CI: 1.81-10.5). Other risk factors included age, place of residence, education, number of births, lifetime number of sexual partners, and time in present relationship. HIV risk factors among urban and rural women and among HPV-positive and HPV-negative women were similar. HPV vaccination may provide some protection against HIV infection in Tanzania, but focus must still be on preventing established risk factors for HIV. PMID- 27379613 TI - The first breath during resuscitation of prematurely born infants. AB - BACKGROUND: The first five initial inflation pressures and times during resuscitation of prematurely born infants are frequently lower than those recommended and rarely result in tidal volumes exceeding the anatomical dead space. Greater volumes were produced when the infant was provoked to inspire by an inflation (active inflation). AIMS: To assess factors associated with a shorter time to the first active inflation. STUDY DESIGN: Respiratory function monitoring was undertaken during resuscitation, peak inflation pressures (PIP), inflation times and the infant's respiratory activity were simultaneously recorded. SUBJECTS: Infants with a gestational age<34weeks requiring resuscitation at birth. OUTCOME MEASURES: The relationships of the PIP and inflation time of the first five inflations and first active inflation to the time to the first active inflation. RESULTS: Recordings from 47 infants, median gestational age of 29 (23-34) weeks, were analysed. The median PIP of the first five inflations was 27 (range 9-37) cmH2O and inflation time 1.22 (range 0.32 4.08) s. The median PIP of the first active inflation was 25 (range 19-37) cmH2O and inflation time 1.35 (0.35-3.67) s. The median time to the first active inflation was 7 (range 0-50) seconds and was inversely correlated with the PIP (p=0.001) and inflation time (p=0.018) of the first five inflations and the PIP (p=0.001) and inflation time (p=0.008) of the first active inflation. CONCLUSION: The magnitude of the inflation pressures and times of the first five inflations inversely correlate with the time to the first breath during resuscitation. PMID- 27379615 TI - A fast algorithm for calculating an expected outbreak size on dynamic contagion networks. AB - Calculation of expected outbreak size of a simple contagion on a known contact network is a common and important epidemiological task, and is typically carried out by computationally intensive simulation. We describe an efficient exact method to calculate the expected outbreak size of a contagion on an outbreak invariant network that is a directed and acyclic, allowing us to model all dynamically changing networks when contagion can only travel forward in time. We describe our algorithm and its use in pseudocode, as well as showing examples of its use on disease relevant, data-derived networks. PMID- 27379614 TI - Affective lability and difficulties with regulation are differentially associated with amygdala and prefrontal response in women with Borderline Personality Disorder. AB - The present neuroimaging study investigated two aspects of difficulties with emotion associated with Borderline Personality Disorder (BPD): affective lability and difficulty regulating emotion. While these two characteristics have been previously linked to BPD symptomology, it remains unknown whether individual differences in affective lability and emotion regulation difficulties are subserved by distinct neural substrates within a BPD sample. To address this issue, sixty women diagnosed with BPD were scanned while completing a task that assessed baseline emotional reactivity as well as top-down emotion regulation. More affective instability, as measured by the Affective Lability Scale (ALS), positively correlated with greater amygdala responses on trials assessing emotional reactivity. Greater difficulties with regulating emotion, as measured by the Difficulties with Emotion Regulation Scale (DERS), was negatively correlated with left Inferior Frontal Gyrus (IFG) recruitment on trials assessing regulatory ability. These findings suggest that, within a sample of individuals with BPD, greater bottom-up amygdala activity is associated with heightened affective lability. By contrast, difficulties with emotion regulation are related to reduced IFG recruitment during emotion regulation. These results point to distinct neural mechanisms for different aspects of BPD symptomology. PMID- 27379616 TI - Repositioning of anti-viral drugs as therapy for cervical cancer. AB - BACKGROUND: Increase in expression of eIF4E (Eukaryotic translation initiation factor 4E) protein is mediated by oncogenic proteins of Human Papilloma Virus (HPV). Increased expression of eIF4E plays an important role in HPV induced carcinogenesis. Ribavirin and Indinavir are known inhibitors of eIF4E activity. METHODS: The effect of the drugs on HeLa cells was assessed by in vitro assays including cell viability using MTT and Neutral red assay, apoptotic potential using Caspase-3, Caspase-8 and Caspase-9 activity assays and MMP-2 and MMP-9 secretion by determination of Gelatinase activity. The in vivo effect of Ribavirin treatment on tumor volume was assessed in human xenograft in immunocompromised C57BL/6 mice. RESULTS: In vitro analyses indicate that Ribavirin and Indinavir reduce viability of HeLa cells, induce apoptosis and decrease secretion of MMPs. Treatment with Ribavirin at a dose of 50mg/kg and 100mg/kg daily led to significant decrease in tumor volume in vivo. CONCLUSION: The study thus provides evidence that Ribavirin and Indinavir can be explored as therapy against HPV-18 induced cervical cancer. PMID- 27379617 TI - Silenced rice in both cytosolic ascorbate peroxidases displays pre-acclimation to cope with oxidative stress induced by 3-aminotriazole-inhibited catalase. AB - The maintenance of H2O2 homeostasis and signaling mechanisms in plant subcellular compartments is greatly dependent on cytosolic ascorbate peroxidases (APX1 and APX2) and peroxisomal catalase (CAT) activities. APX1/2 knockdown plants were utilized in this study to clarify the role of increased cytosolic H2O2 levels as a signal to trigger the antioxidant defense system against oxidative stress generated in peroxisomes after 3-aminotriazole-inhibited catalase (CAT). Before supplying 3-AT, silenced APX1/2 plants showed marked changes in their oxidative and antioxidant profiles in comparison to NT plants. After supplying 3-AT, APX1/2 plants triggered up-expression of genes belonging to APX (OsAPX7 and OsAPX8) and GPX families (OsGPX1, OsGPX2, OsGPX3 and OsGPX5), but to a lower extent than in NT plants. In addition, APX1/2 exhibited lower glycolate oxidase (GO) activity, higher CO2 assimilation, higher cellular integrity and higher oxidation of GSH, whereas the H2O2 and lipid peroxidation levels remained unchanged. This evidence indicates that redox pre-acclimation displayed by silenced rice contributed to coping with oxidative stress generated by 3-AT. We suggest that APX1/2 plants were able to trigger alternative oxidative and antioxidant mechanisms involving signaling by H2O2, allowing these plants to display effective physiological responses for protection against oxidative damage generated by 3-AT, compared to non-transformed plants. PMID- 27379620 TI - "Whole-of-Community" Obesity Prevention: A Review of Challenges and Opportunities in Multilevel, Multicomponent Interventions. AB - The causes of obesity worldwide are complex and multilevel, including changing food environments, physical activity levels, policies, and food production systems. This intricate context requires multilevel and multicomponent (MLMC) interventions to improve health outcomes. We conducted a literature review of MLMC interventions for obesity prevention and mitigation; 14 studies meeting search criteria were identified. We found examples of successes in preventing obesity, reducing overweight, improving healthful behaviors, and enhancing some psychosocial indicators. Of eight studies that reported health and behavioral results, five showed no significant impact and three showed reductions in obesity. Four studies showed significant improvement in dietary behavior, and five reported significant desirable effects in physical activity or screen time. Five studies reported psychosocial impacts, and three of these showed significant improvements. MLMC approaches show promising results, particularly when they are able to integrate components at the policy, community, and interpersonal levels. PMID- 27379618 TI - Executive function deficits associated with current and past major depressive symptoms. AB - BACKGROUND: Although there has been extensive research showing that depression is associated with executive function (EF) deficits, the nature of these deficits is not clearly delineated. Specifically, previous reviews on this topic have yielded different conclusions about the particular domains of EF that are disrupted in depressed individuals. Further, research on whether these deficits persist after depressed mood has remitted is less prevalent and not consistent. METHODS: In two independent samples of college students, we examined associations between clinical ratings of current and past symptoms of a Major Depressive Episode (MDE) and difficulties in two domains of EF: inhibition and shifting. In Study 1 (n=162), EF was measured using behavioral tasks shown to index these two domains. In Study 2 (n=95), EF was measured using a self-report questionnaire believed to capture EF difficulties experienced in daily life. RESULTS: In both studies, past MDE symptoms were associated with worse shifting. In contrast, current MDE symptoms were associated with worse inhibition, though only on the behavioral measure (in Study 1). LIMITATIONS: Both studies used college samples and retrospective assessments of past symptoms. Further, only two domains of EF were examined, and the EF measures employed in each study have their own unique methodological limitations. CONCLUSIONS: Findings suggest that inhibition deficits vary as a function of current symptoms and thus may be a by-product of distress rather than a causal contributor. In contrast, shifting deficits associated with depression appear to be more enduring, suggesting that they could contribute to risk for depression. PMID- 27379621 TI - [Grading of neuroendocrine tumors]. AB - The current WHO classification of neuroendocrine tumors (NET) differentiates between typical carcinoids (low grade NET), atypical carcinoids (intermediate grade NET) and small cell and large cell carcinomas (high grade NET) according to the prognosis. Neuroendocrine neoplasms (NEN) of the gastrointestinal tract and the pancreas are graded in an identical way. Together with the TNM system this enables a preoperative estimation of the prognosis in biopsies and fine needle aspirates. Well-differentiated tumors are graded into G1 tumors by the number of mitoses, <2 per 10 high-power fields (HPF) and the Ki-67 (index <3 %) and G2 tumors (2-20 mitoses/10 HPF, Ki-67 3-20 %). Discrepancies between the number of mitoses and the Ki-67 index are not uncommon and in these cases the higher value of the two should be applied. The more differentiated tumors of the G3 type have to be differentiated from undifferentiated carcinomas of the small cell type and large cell type with a much poorer prognosis. Prognosis relevant grading of thyroid cancers is achieved by special subtyping so that the G1-G3 system is not applicable. The rare cancers of the parathyroid gland and of the pituitary gland are not graded. Adrenal tumors also have no grading system. The prognosis is dependent on the Ki-67 index and with some reservations on the established scoring systems. PMID- 27379623 TI - Bilateral renal cancers: oncological and functional outcomes. AB - PURPOSE: The authors assessed the characteristics of bilateral renal cancers. METHODS: From January 1995 to January 2015, 65 patients underwent surgery for bilateral renal cancers. Thirty-four of the patients had 36 synchronous tumors, while the remaining 29 had metachronous tumors. The mean age of the patients was 60 +/- 11 years. There were 22 females and 43 males. In all cases, bilateral partial nephrectomies or unilateral nephrectomy and contralateral nephron-sparing surgery were performed. RESULTS: The mean sizes of the synchronous tumors were 5.0 +/- 2.7 and 4.7 +/- 3.0 cm at the first and the second operations, respectively. The average diameters of the metachronous carcinomas were 6.6 +/- 3.0 and 3.1 +/- 1.6 cm at the initial and the second surgeries, respectively. Histologic concordance was 91.1 % in the synchronous and 96.5 % in the metachronous tumors. The mean postoperative creatinine levels increased by 116 %, while the GFR decreased by 44.8 % in synchronous tumors at the second operation. The mean postoperative creatinine levels increased by 42 %, while the GFR decreased by 30.4 % in metachronous carcinomas at the second operation. The mean follow-up time was 4.8 +/- 3.7 years. During this period, distant metastases occurred in two patients with synchronous tumors and in six cases with metachronous tumors. Local recurrences were detected in one case of synchronous tumor and in four patients with metachronous carcinomas. The 5-year overall and tumor-specific survivals were 53 and 80 %, respectively. CONCLUSIONS: In patients with bilateral renal carcinomas, the histologic concordance was 93.6 %. The bilateral partial nephrectomies or unilateral nephrectomy and contralateral resection provided acceptable oncological and functional outcomes. PMID- 27379624 TI - Clinical factors associated with constipation in hemodialysis patients. PMID- 27379622 TI - [Grading of gynecological tumors : Current aspects]. AB - Histopathological assessment of the tumor grade and cell type is central to the management and prognosis of various gynecological malignancies. Conventional grading systems for squamous carcinomas and adenocarcinomas of the vulva, vagina and cervix are poorly defined. For endometrioid tumors of the female genital tract as well as for mucinous endometrial, ovarian and seromucinous ovarian carcinomas, the 3-tiered FIGO grading system is recommended. For uterine neuroendocrine tumors the grading system of the gastrointestinal counterparts has been adopted. Uterine leiomyosarcomas are not graded. Endometrial stromal sarcomas are divided into low and high grades, based on cellular morphology, immunohistochemical and molecular findings. A chemotherapy response score was established for chemotherapeutically treated high-grade serous pelvic cancer. For non-epithelial ovarian malignancies, only Sertoli-Leydig cell tumors and immature teratomas are graded. At this time molecular profiling has no impact on the grading of tumors of the female genital tract. PMID- 27379626 TI - Effects of modified penoplasty for concealed penis in children. AB - PURPOSE: To evaluate the effect of modified penoplasty in the management of concealed penis. METHODS: We retrospectively reviewed 96 consecutive patients with concealed penis, which had been surgically corrected between July 2013 and July 2015. All patients underwent modified Shiraki phalloplasty. All patients were scheduled for regular follow-up at 1, 3, and 6 months after the surgery. Data on the patients' age, operative time, postoperative complications, and parents' satisfaction grade were collected and analyzed. RESULTS: The mean follow up period was 17.4 months (range 7-31 months). The mean operative time was 63.2 +/- 8.7 min. The mean perpendicular penile length was 1.89 +/- 0.77 cm preoperatively and 4.42 +/- 0.87 cm postoperatively, with an improved mean length of 2.5 +/- 0.68 cm in the flaccid state postoperatively (p < 0.05). The patients' satisfaction grades after the surgery were improved significantly (p < 0.05). Fifty-two patients had penile lymphedema postoperatively; however, it disappeared spontaneously within 3 months. Additionally, postoperative wound infection occurred in two patients. There were no complications such as flap necrosis, penile shaft contracture, voiding difficulty, and erection difficulties. CONCLUSION: The modified Shiraki phalloplasty for concealed penis can achieve maximum utilization of prepuce to assure coverage of the exposed penile shaft. It has fewer complications, achieving marked asthetics, and functional improvement. It is a relatively ideal means for treating concealed penis. PMID- 27379625 TI - Comparison of high-flux hemodialysis with hemodialysis filtration in treatment of uraemic pruritus: a randomized controlled trial. AB - PURPOSE: Uraemic pruritus (UP) is one of the most common complications in patients with end-stage renal disease (ESRD) undergoing dialysis and greatly undermines their quality of life. The present study was designed to compare the clinical effect of high-flux hemodialysis (HFHD) with hemodialysis filtration (HDF) in the treatment of UP in ESRD patients, and to explore the possible underlying mechanisms. MATERIALS AND METHODS: In this 12-week randomized and controlled trial, the clinical efficacy of HFHD or HDF on UP patients undergoing dialysis was evaluated. A total of 51 uremia patients suffering from pruritus from January 2009 to May 2013 were recruited and randomly assigned to intervention (n = 27) and control (n = 24) groups. The control group was received only HDF therapy, and the intervention group underwent HFHD treatment three times a week for 12 weeks. RESULTS: The scores for Visual Analogue Scale in both two groups were obviously decreased, but the Visual Analogue Scale scores in the intervention group had a better improvement than the control group within 12 weeks. The PSQI and SF-12 values in the intervention group had a better improvement than the control group within 12 weeks. In comparison of the changes from baseline between the control groups, there was greater improvement in BUN, creatinine, calcium, phosphorus, PTH, beta2-MG, histamine, CRP and IL-6 levels of intervention group. CONCLUSIONS: Our results demonstrate that HFHD has a better efficacy in the treatment of UP than HDF. HFHD has an exactly therapeutical efficacy in the UP associated with the inhibition of microinflammation state in dialysis patients. PMID- 27379627 TI - Bioprosthetic mesh of bacterial cellulose for treatment of abdominal muscle aponeurotic defect in rat model. AB - The use of meshes for treatment of hernias continues to draw attention of surgeons and the industry in the search of an ideal prosthesis. The purpose of this work is to use meshes manufactured from bacterial cellulose, evaluate their organic tissue interaction and compare with an expanded polytetrafluorethylene (ePTFE's) prosthesis used to repair acute defect of muscle aponeurotic induced in rats. Forty-five male Wistar rats were classified using the following criteria: (1) surgical repair of acute muscle aponeurotic defect with perforated bacterial cellulose film (PBC; n = 18); (2) compact bacterial cellulose film (CBC; n = 12) and (3) ePTFE; (n = 15). After postoperative period, rectangles (2 * 3 cm) including prosthesis, muscles and peritoneum were collected for biomechanical, histological and stereological analysis. In all cases, the maximum acceptable error probability for rejecting the null hypothesis was 5 %. Between PBC and CBC samples, the variables of strain (P = 0.011) and elasticity (P = 0.035) were statistically different. The same was found between CBC and ePTFE (elasticity, P = 0.000; strain, P = 0.009). PBC differed from CBC for giant cells (P = 0.001) and new blood vessels (P = 0.000). In conclusion, there was biological integration and biomechanical elasticity of PBC; therefore, we think this option should be considered as a new alternative biomaterial for use as a bio prosthesis. PMID- 27379628 TI - In vitro investigation of nanohydroxyapatite/poly(L-lactic acid) spindle composites used for bone tissue engineering. AB - Calcium phosphate ceramics such as synthetic hydroxyapatite and tricalcium phosphate are widely used in the clinic, but they stimulate less bone regeneration. In this paper, nano-hydroxyapatite/poly(L-lactic acid) (nano HA/PLLA) spindle composites with good mechanical performance were fabricated by a modified in situ precipitation method. The HA part of composite, distributing homogenously in PLLA matrix, is spindle shape with size of 10-30 nm in diameter and 60-100 nm in length. The molar ratio of Ca/P in the synthesized nano-HA spindles was deduced as 1.52 from the EDS spectra, which is close to the stoichiometric composition of HA (Ca/P & 1.67). The compress strength is up to 150 MPa when the HA content increase to 20 %. The in vitro tests indicate that HA/PLLA bio-composites have good biodegradability and bioactivity when immersed in simulated body fluid solutions. All the results suggested that HA/PLLA nano biocomposites are appropriate to be applied as bone substitute in bone tissue engineering. PMID- 27379629 TI - Memories and Promises of the Enteric Nervous System and Its Functions. AB - This is a very personal reminiscence of the long period of Enteric Nervous System research in which I have been involved. I started to work on the gut in the early 60s really because in Turin when I arrived from Argentina, where my family migrated temporarily after the WWII, nobody was seriously working on the brain. In Anatomy they were studying the neural "intramural plexuses" and that for me was close enough to the nervous system. I grew up in the mountains near Turin near the French border where our ex-family house still bears our name. I joined the Department of Anatomy as an intern student and I was privileged to seat at a desk where a previous generation of young scientists, who studied under the professor of Anatomy A. Levi, the founder of the methods for culturing neural tissue. They were Salvador Luria, Renato Dulbecco and Rita Levi-Montalcini, who, after migrating to the USA, were each were given the Noble prize. PMID- 27379630 TI - A Personal Perspective on the Development of Our Understanding of the Myogenic Control Mechanisms of Gut Motor Function. AB - Myogenic control mechanisms play a role in all motor activities of the gut. Myogenic control systems are defined here as control systems that are intrinsic to the smooth muscle cells and/or interstitial cells of Cajal (ICC) and that can operate without an essential contribution of the intrinsic (ENS) and extrinsic nervous systems. In vivo however, the ENS and the myogenic control systems always work in cooperation. Although myogenic control plays a role in every gut organ, this review focuses on the peristaltic and segmentation activity of the small intestine. It provides some historical perspectives and some discussion on the development of our understanding of the cooperative nature of the myogenic and neurogenic control mechanisms. It highlights how some influential papers inadvertently provided hindrance to full understanding, it discusses how the guinea pig model has hampered acceptance of myogenic control systems and it provides some background into the genesis of our understanding of control mechanisms involving ICC. PMID- 27379631 TI - Enteric Inhibitory Neurotransmission, Starting Down Under. AB - The idea of an inhibitory innervation in the gut came from Geoff Burnstock's group at the University of Melbourne in the 1960s. Being resistant to antagonists of norepinephrine and acetylcholine, enteric inhibitory neurotransmission became known as non-cholinergic, non-adrenergic (NANC) neurotransmission. ATP (or a closely related nucleotide) was proposed as the inhibitory neurotransmitter based on release of purines during nerve stimulation and similarities between responses to ATP and transmural nerve stimulation in several gut preparations. Apamin was found to block purinergic responses, providing evidence that small-conductance Ca(2+)-activated K(+) (SK) channels were responsible for inhibitory junction potentials (IJPs). Actually the IJPs in GI muscles are composed of multiple components, and later studies discovered nitric oxide (NO) to be the other major mediator of NANC inhibitory neurotransmission. The purinergic component of enteric inhibitory neurotransmission is mediated by P2Y1 receptors, and this component is absent in P2Y1(-/-) mice. The criteria for a neurotransmitter are better met by beta-nicotinamide adenine dinucleotide (beta-NAD) or its immediate metabolite ADP-ribose (ADPR) than by ATP. The cells mediating post-junctional responses have been identified. In addition to smooth muscle cells, two classes of interstitial cells express receptors and effectors for NANC neurotransmitters and are electrically coupled to smooth muscle cells. This integrated structure has been named the SIP syncytium. Interstitial cells of Cajal are involved in transduction of cholinergic and nitrergic inputs to GI muscles, and PDGFRalpha(+) cells mediate purinergic effects. This short symposium report summarizes major historical points of interest and some of the more recent findings related to enteric inhibitory neurotransmission. PMID- 27379632 TI - Spatio-Temporal Mapping and the Enteric Nervous System. AB - Study of the enteric nervous system (ENS) is somewhat less glamorous than other body systems but offers a unique opportunity to study the sensory, interneuronal and motor outputs of a highly developed neural network in the same tissue. This has not been a trivial task, and even after a century, we still struggle to understand both the simple (e.g. reflexes) and complex (e.g. MMCs) behaviors the gut produces. On top of that, other control networks (such as ICC) that are integrated with ENS at varying levels, can modify ENS activity directly or indirectly. While many of the methods used to study the ENS were originally developed in other systems (e.g. brain/heart), a few were spawned "in the offal" so to speak, due to the unique characteristics of the gut. The brief perspective below outlines how spatio-temporal maps (ST Maps) originated and continue to flourish in GI research as a tool to describe and analyze the complexity of GI movements.I apologize that I am not able to specifically mention all the people involved in the development and use of ST Maps in enteric/motility research due to space constraints (GWH, July 2014). PMID- 27379633 TI - Development of Neural Activity in the Enteric Nervous System: Similarities and Differences to Other Parts of the Nervous System. AB - All the neurons and glia of the enteric nervous system (ENS) arise from neural crest-derived cells that migrate into the gastrointestinal (GI) tract during development (Yntema and Hammond 1954; Le Douarin and Teillet 1973). Most of the ENS originates from vagal neural crest cells (NCCs), which arise from the caudal hindbrain region of the neural tube, adjacent to somites 1-7. In the developing mouse, vagal NCCs migrate into the developing oesophagus and stomach at embryonic day (E)9.5, enter the small intestine at E10.5, and colonise the developing GI tract in a rostral-to-caudal wave, reaching the anal end of the colon at E14.5 (Serbedzija et al. 1991; Kapur et al. 1992; Anderson et al. 2006). Recent evidence indicates that there is also trans-mesenteric migration of vagal NCCs, where some NCCs leave the small intestine and migrate directly across the mesentery into the colon (Nishiyama et al. 2012). Sacral NCCs also contribute to a small population of neurons and glia in the colon (Burns and Le Douarin 1998; Wang et al. 2011). PMID- 27379634 TI - ENS Development Research Since 1983: Great Strides but Many Remaining Challenges. AB - The first enteric nervous system (ENS) conference, organized by Marcello Costa and John Furness, was held in Adelaide, Australia in 1983. In this article, we review what was known about the development of the ENS in 1983 and then summarize some of the major advances in the field since 1983. PMID- 27379635 TI - Extrinsic Sensory Innervation of the Gut: Structure and Function. AB - Extrinsic sensory neurons play a key role in the function of the gastrointestinal tract. They are responsible for the sensations that arise in the gut and can initiate automatic reflexes. In some cases, disordered sensation is clinically problematic-pain, bloating, excessive urgency and nausea are well-known examples. Major advances have been made in understanding the function of somatic sensory neurons in the last 50 years. However, the sensory neurons that mediate sensations from the viscera remain less well understood. This is partly because viscera receive a dense autonomic innervation that can be difficult to separate from extrinsic sensory neurons. A key requirement to understand the genesis of sensation is to distinguish the different classes of sensory neurons and the types of stimuli which they encode. The aim of this short paper is to summarise what was known about these matters 30 years ago and highlight some of the major advances in the understanding of the types of extrinsic sensory neurons to the gut. Necessarily, the choice of papers is somewhat idiosyncratic, but they illustrate the range of advances that have been made in distinguishing the different classes of gastrointestinal afferent nerves. PMID- 27379636 TI - Ageing and Gastrointestinal Sensory Function. AB - Over the past few decades a combination of electrophysiological, morphological and molecular approaches has enabled the different populations of vagal and spinal afferents that innervate the bowel to be characterized. The sensitivity of these afferents is determined by their location in the gut wall, their relationship with other cells and structures and the receptors and ion channels that they express on their nerve terminals. An important feature of this innervation is that it is upregulated during injury, inflammation and ischaemia through changes in receptors and ion channels that determine excitability and sensitivity. In recent studies we have sought to identify how sensory mechanisms are influenced as part of the normal ageing process. Attenuated signaling was evident in different gastrointestinal afferent subpopulations conveying low and high threshold mechanosensory information and there was impairment in the ability of sensory neurons to sensitize in response to chemical mediators such as 5-HT. These sensory deficits may contribute to altered bowel habits with age and the prevalence of incontinence in the elderly. PMID- 27379637 TI - Altered Ion Channel/Receptor Expression and Function in Extrinsic Sensory Neurons: The Cause of and Solution to Chronic Visceral Pain? AB - The gastrointestinal tract is unique in that it is innervated by several distinct populations of neurons, whose cell bodies are either intrinsic (enteric, viscerofugal) or extrinsic (sympathetic, sensory afferents) to the wall of the gut. We are usually completely unaware of the continuous, complicated orchestra of functions that these neurons conduct. However, for patients with Inflammatory Bowel Disease (IBD) or functional gastrointestinal disorders, such as Functional Dyspepsia (FD) and Irritable Bowel Syndrome (IBS) altered gastrointestinal motility, discomfort and pain are common, debilitating symptoms. Whilst bouts of inflammation underlie the symptoms associated with IBD, over the past few years there is increased pre-clinical and clinical evidence that infection and inflammation are key risk factors for the development of several functional gastrointestinal disorders, in particular IBS. There is a strong correlation between prior exposure to gut infection and symptom occurrence; with the duration and severity of the initial illness the strongest associated risk factors. This review discusses the current body of evidence for neuroplasticity during inflammation and how in many cases fails to reset back to normal, long after healing of the damaged tissues. Recent evidence suggests that the altered expression and function of key ion channels and receptors within extrinsic sensory neurons play fundamental roles in the aberrant pain sensation associated with these gastrointestinal diseases and disorders. PMID- 27379638 TI - Purinergic Signalling in the Gut. AB - The article will begin with the discovery of purinergic inhibitory neuromuscular transmission in the 1960s/1970s, the proposal for purinergic cotransmission in 1976 and the recognition that sympathetic nerves release adenosine 5' triphosphate (ATP), noradrenaline and neuropeptide Y, while non-adrenergic, non cholinergic inhibitory nerve cotransmitters are ATP, nitric oxide and vasoactive intestinal polypeptide in variable proportions in different regions of the gut. Later, purinergic synaptic transmission in the myenteric and submucosal plexuses was established and purinergic receptors expressed by both glial and interstitial cells. The focus will then be on purinergic mechanosensory transduction involving release of ATP from mucosal epithelial cells during distension to activate P2X3 receptors on submucosal sensory nerve endings. The responses of low threshold fibres mediate enteric reflex activity via intrinsic sensory nerves, while high threshold fibres initiate pain via extrinsic sensory nerves. Finally, the involvement of purinergic signalling in an animal model of colitis will be presented, showing that during distension there is increased ATP release, increased P2X3 receptor expression on calcitonin gene-related peptide-labelled sensory neurons and increased sensory nerve activity. PMID- 27379639 TI - Is There a Role for Endogenous 5-HT in Gastrointestinal Motility? How Recent Studies Have Changed Our Understanding. AB - Over the past few years, there have been dramatic changes in our understanding of the role of endogenous 5-hydroxytryptamine (5-HT) in the generation of gastrointestinal (GI) motility patterns in the small and large intestine. The idea that endogenous 5-HT played a major role in the generation of peristalsis in the small intestine was first proposed in the mid 1950s, after it was discovered that endogenous 5-HT could be released from the mucosa at a similar time that peristalsis occurred; and that exogenous 5-HT could potently stimulate peristalsis. The fact that exogenous 5-HT stimulated peristalsis and that there was a similarity in timing between the release of 5-HT from the mucosa and the onset of peristalsis led investigators to propose that release of endogenous 5-HT from the mucosa was causally related to the generation of peristalsis. In further support of this, other studies showed that selective 5-HT antagonists could inhibit or block peristalsis, and other motor patterns, such as the migrating motor complex. Taken together, based on these findings, some laboratories believed that endogenous 5-HT (synthesized in the gut wall) was an important mediator, or initiator, of different propulsive motor patterns in the lower GI tract. This notion changed dramatically in the past few years, however, after it was discovered that removal of the mucosa abolished all cyclical release of endogenous 5-HT, but did not block peristalsis, nor the cyclical migrating complex. Furthermore, other laboratories revealed that genetic deletion of the gene tryptophan hydroxylase 1 (TPH-1) (that synthesizes endogenous 5-HT in the mucosa) actually had no inhibitory effect on transit of intestinal contents in live animals. Then, perhaps one of the most startling of all observations was the discovery that selective 5-HT receptor antagonists actually have the same inhibitory effects on peristalsis and the migrating complex in segments of intestine that had been depleted of all endogenous 5-HT. Taken together, these recent findings have led to a major revision in our understanding of the functional role of endogenous 5-HT in the generation of propulsive motor patterns in the lower GI tract. This review will focus on how our understanding of endogenous 5-HT in the GI tract has changed substantially in recent times. PMID- 27379640 TI - Enteric neuropathies: Yesterday, Today and Tomorrow. AB - Enteric neuropathy is a term indicating an impairment of the innervation supplying the gastrointestinal tract. The clinical phenotypes of the enteric neuropathies are the 'tip of the iceberg' of severe functional digestive diseases, such as intestinal pseudo-obstruction syndromes (e.g., chronic intestinal pseudo-obstruction). Despite progress acquired over the years, the pathogenetic mechanisms leading to enteric neuropathies are still far from being elucidated and the therapeutic approaches to these patients are mainly supportive, rather than curative.The purpose of this chapter is to review the advancements that have been done in the knowledge of enteric neuropathies identified in adult patients ('tomorrow'), going through where we currently are ('today') following a brief history of the major milestones on the pioneering discoveries in the field ('yesterday'). PMID- 27379641 TI - Postnatal Development of the Mouse Enteric Nervous System. AB - Owing to over three decades of research, we now have a good understanding of the genetic and molecular control of enteric nervous system (ENS) development during embryonic and prenatal stages. On the other hand, it has only just become clear that a substantial process of ENS maturation occurs after birth (Hao et al. 2013a). During postnatal stages, in addition to genetic influences, ENS development is also potentially affected by the external environment. Thus it is possible that manipulating certain environmental factors could help prevent or reduce motility disorders. However the genetic and environmental factors that regulate postnatal ENS development remain unknown. Researchers have used a variety of animal models that are easy to manipulate genetically or experimentally, and have short gestational periods, to understand the development of the ENS. Notably, due to the availability of mouse models for several human enteric neuropathies, many studies have used the mature and developing murine ENS as a model. Here, I will discuss recent advances in knowledge about postnatal development of the murine ENS, and highlight future directions for this emerging research field. PMID- 27379642 TI - G Protein-Coupled Receptor Trafficking and Signalling in the Enteric Nervous System: The Past, Present and Future. AB - G protein-coupled receptors (GPCRs) enable cells to detect and respond to changes in their extracellular environment. With over 800 members, the GPCR family includes receptors for a diverse range of agonists including olfactants, neurotransmitters and hormones. Importantly, GPCRs represent a major therapeutic target, with approximately 50 % of all current drugs acting at some aspect of GPCR signalling (Audet and Bouvier 2008). GPCRs are widely expressed by all cell types in the gastrointestinal (GI) tract and are major regulators of every aspect of gut function. Many GPCRs are internalised upon activation, and this represents one of the mechanisms through which G protein-signalling is terminated. The latency between the endocytosis of GPCRs and their recycling and resensitization is a major determinant of the cell's ability to respond to subsequent exposure to agonists. PMID- 27379643 TI - The Intrinsic Reflex Circuitry of the Inflamed Colon. AB - In 1899, Bayliss and Starling determined that the innervation of the intestines differs from that of other organs. They found that local neuronal networks are capable of generating reflex responses without the involvement of the central nervous system (Bayliss and Starling 1899). Once this unique feature of the enteric nervous system (ENS) was identified, it took roughly a century for enteric neurobiologists to accomplish the task of being able to identify the components of this "intrinsic neural mechanism", including intrinsic primary afferent neuron, ascending and descending interneuron, and excitatory and inhibitory motor neurons (Bayliss and Starling 1899). Once this was possible, we and others began to investigate the intrinsic circuitry of the colon and ileum to systematically determine the cellular mechanisms that explain the changes in motility and secretion that occur in intestinal inflammation. We wanted to establish what changes occur in the enteric neural circuitry, where they occur, the mechanisms responsible for these changes, and how these changes in the neural circuitry impact intestinal function. PMID- 27379644 TI - Integrated Neural and Endocrine Control of Gastrointestinal Function. AB - The activity of the digestive system is dynamically regulated by external factors, including body nutritional and activity states, emotions and the contents of the digestive tube. The gut must adjust its activity to assimilate a hugely variable mixture that is ingested, particularly in an omnivore such as human for which a wide range of food choices exist. It must also guard against toxins and pathogens. These nutritive and non-nutritive components of the gut contents interact with the largest and most vulnerable surface in the body, the lining of the gastrointestinal tract. This requires a gut sensory system that can detect many classes of nutrients, non-nutrient components of food, physicochemical conditions, toxins, pathogens and symbionts (Furness et al., Nat Rev Gastroenterol Hepatol 10:729-740, 2013). The gut sensors are in turn coupled to effector systems that can respond to the sensory information. The responses are exerted through enteroendocrine cells (EEC), the enteric nervous system (ENS), the central nervous system (CNS) and the gut immune and tissue defence systems. It is apparent that the control of the digestive organs is an integrated function of these effectors. The peripheral components of the EEC, ENS and CNS triumvirate are extensive. EEC cells have traditionally been classified into about 12 types (disputed in this review), releasing about 20 hormones, together making the gut endocrine system the largest endocrine organ in the body. Likewise, in human the ENS contains about 500 million neurons, far more than the number of neurons in the remainder of the peripheral autonomic nervous system. Together gut hormones, the ENS and the CNS control or influence functions including satiety, mixing and propulsive activity, release of digestive enzymes, induction of nutrient transporters, fluid transport, local blood flow, gastric acid secretion, evacuation and immune responses. Gut content receptors, including taste, free fatty acid, peptide and phytochemical receptors, are primarily located on EEC. Hormones released by EEC act via both the ENS and CNS to optimise digestion. Toxic chemicals and pathogens are sensed and then avoided, expelled or metabolised. These defensive activities also involve the EEC and signalling from EEC to the ENS and the CNS. A major challenge is to develop a comprehensive understanding of the integrated responses of the gut, via its effector systems, the ENS, extrinsic innervation, EEC and the gut immune system, to the sensory information it receives. PMID- 27379645 TI - Enteric Neurobiology: Discoveries and Directions. AB - Discovery and documentation of noncholinergic-nonadrenergic neurotransmission in the enteric nervous system started a revolution in mechanisms of neural control of the digestive tract that continues into a twenty-first century era of translational gastroenterology, which is now firmly embedded in the term, neurogastroenterology. This chapter, on Enteric Neurobiology: Discoveries and Directions, tracks the step-by-step advances in enteric neuronal electrophysiology and synaptic behavior and progresses to the higher order functions of central pattern generators, hard wired synaptic circuits and libraries of neural programs in the brain-in-the-gut that underlie the several different patterns of motility and secretory behaviors that occur in the specialized, serially-connected compartments extending from the esophagus to the anus. PMID- 27379646 TI - Advanced 3D Optical Microscopy in ENS Research. AB - Microscopic techniques are among the few approaches that have survived the test of time. Being invented half way the seventeenth century by Antonie van Leeuwenhoek and Robert Hooke, this technology is still essential in modern biomedical labs. Many microscopy techniques have been used in ENS research to guide researchers in their dissections and later to enable electrode recordings. Apart from this, microscopy has been instrumental in the identification of subpopulations of cells in the ENS, using a variety of staining methods. A significant step forward in the use of microscopy was the introduction of fluorescence approaches. Due to the fact that intense excitation light is now filtered away from the longer wavelength emission light, the contrast can be improved drastically, which helped to identify subpopulations of enteric neurons in a variety of species. Later functionalized fluorescent probes were used to measure and film activity in muscle and neuronal cells. Another important impetus to the use of microscopy was the discovery and isolation of the green fluorescent protein (GFP), as it gave rise to the development of many different color variants and functionalized constructs. Recent advances in microscopy are the result of a continuous search to enhance contrast between the item of interest and its background but also to improve resolving power to tell two small objects apart. In this chapter three different microscopy approaches will be discussed that can aid to improve our understanding of ENS function within the gut wall. PMID- 27379647 TI - Excitability and Synaptic Transmission in the Enteric Nervous System: Does Diet Play a Role? AB - Changes in diet are a challenge to the gastrointestinal tract which needs to alter its processing mechanisms to continue to process nutrients and maintain health. In particular, the enteric nervous system (ENS) needs to adapt its motor and secretory programs to deal with changes in nutrient type and load in order to optimise nutrient absorption.The nerve circuits in the gut are complex, and the numbers and types of neurons make recordings of specific cell types difficult, time-consuming, and prone to sampling errors. Nonetheless, traditional research methods like intracellular electrophysiological approaches have provided the basis for our understanding of the ENS circuitry. In particular, animal models of intestinal inflammation have shown us that we can document changes to neuronal excitability and synaptic transmission.Recent studies examining diet-induced changes to ENS programming have opted to use fast imaging techniques to reveal changes in neuron function. Advances in imaging techniques using voltage- or calcium-sensitive dyes to record neuronal activity promise to overcome many limitations inherent to electrophysiological approaches. Imaging techniques allow access to a wide range of ENS phenotypes and to the changes they undergo during dietary challenges. These sorts of studies have shown that dietary variation or obesity can change how the ENS processes information-in effect reprogramming the ENS. In this review, the data gathered from intracellular recordings will be compared with measurements made using imaging techniques in an effort to determine if the lessons learnt from inflammatory changes are relevant to the understanding of diet-induced reprogramming. PMID- 27379648 TI - Recording In Vivo Human Colonic Motility: What Have We Learnt Over the Past 100 Years? AB - To understand the abnormalities that underpin functional gut disorders we must first gain insight into the normal patterns of gut motility. While detailed information continually builds on the motor patterns (and mechanisms that control them) of the human esophagus and anorectum, our knowledge of normal and abnormal motility in the more inaccessible regions of the gut remains poor. This particularly true of the human colon. Investigation of in vivo colonic motor patterns is achieved through measures of transit (radiology, scintigraphy and, more recently, "smart pills") or by direct real-time recording of colonic contractility (intraluminal manometry). This short review will provide an overview of findings from the past and present and attempt to piece together the complex nature of colonic motor patterns. In doing so it will build a profile of human colonic motility and determine the likely mechanisms that control this motility. PMID- 27379649 TI - The Virus of Vagueness in Authorship. PMID- 27379650 TI - Adolescent male chimpanzees do not form a dominance hierarchy with their peers. AB - Dominance hierarchies are a prominent feature of the lives of many primate species. These hierarchies have important fitness consequences, as high rank is often positively correlated with reproduction. Although adult male chimpanzees strive for status to gain fitness benefits, the development of dominance relationships is not well understood. While two prior studies found that adolescent males do not display dominance relationships with peers, additional research at Ngogo in Kibale National Park, Uganda, indicates that adolescents there form a linear dominance hierarchy. These conflicting findings could reflect different patterns of rank acquisition across sites. An alternate possibility arises from a recent re-evaluation of age estimates at Ngogo and suggests that the report describing decided dominance relationships between adolescent males may have been due to the accidental inclusion of young adult males in the sample. To investigate these issues, we conducted a study of 23 adolescent male chimpanzees of known age during 12 months at Ngogo. Adolescent male chimpanzees exchanged pant grunts, a formal signal of submission, only 21 times. Recipients of pant grunts were late adolescent males, ranging between 14 and 16 years old. In contrast, younger adolescent males never received pant grunts from other males. Aggression between adolescent males was also rare. Analysis of pant grunts and aggressive interactions did not produce a linear dominance hierarchy among adolescent males. These data indicate that adolescent male chimpanzees do not form decided dominance relationships with their peers and are consistent with the hypothesis that the hierarchy described previously at Ngogo resulted from inaccurate age estimates of male chimpanzees. Because dominance relationships develop before adulthood in other primates, our finding that adolescent male chimpanzees do not do so is surprising. We offer possible explanations for why this is the case and suggest future studies that may help clarify the matter. PMID- 27379651 TI - Bringing the Family's Voice to Research. PMID- 27379652 TI - Gene expression pattern analysis of a recombinant Escherichia coli strain possessing high growth and lycopene production capability when using fructose as carbon source. AB - OBJECTIVE: Escherichia coli K12f-pACLYC has a high capability for growth and lycopene production when using fructose as carbon source and the transcription of genes involved was compared in glucose-grown and fructose-grown cells. RESULTS: Escherichia coli K12f-pACLYC was grown on 10 g fructose l(-1) and reached 4.6 g DCW l(-1) with lycopene at 192 mg g DCW(-1), values that are 3-fold and 7-fold higher than when growing on glucose. Gene transcription profiles of fructose grown and glucose-grown cells were compared. 384 differentially expressed genes (DEGs) with fold changes >=4 were identified, and the transcription of genes involved in fructose uptake and metabolism, pyruvate catabolism, tricarboxylic acid cycle and oxidative phosphorylation varied significantly. These changes enhanced the metabolic flux into the Embden-Meyerhof-Parnas pathway and the tricarboxylic acid cylcle and coupled to oxidative phosphorylation. These enhanced activities provide more precursors, cofactors and energy needed for growth lycopene production. CONCLUSION: The high capability of E. coli K12f pACLYC for growth and lycopene production when growing on fructose is due to transcriptional regulation, and the relevant genes were identified. PMID- 27379653 TI - Covalent immobilization of Agrobacterium radiobacter epoxide hydrolase on ethylenediamine functionalised epoxy supports for biocatalytical synthesis of (R) epichlorohydrin. AB - OBJECTIVE: To improve the operational stability and reusability of an epoxide hydrolase (EH) for the biosynthesis of optically active epoxides. RESULTS: A covalently immobilization strategy was employed to improve the stability of Agrobacterium radiobacter EH by using ethylenediamine (EDA)-functionalised epoxy resin LX-1000EP as carrier. Under the optimal conditions, the activity recovery of immobilized enzyme was 72 % and the specific activity was 634 U/g. Immobilized EH exhibited significantly enhanced thermal stability with a half-life of more than 6.8-fold at 50 degrees C than that of the free enzyme. A gram-scale kinetic resolution of (R,S)-epichlorohydrin using immobilized preparation as biocatalyst was performed and (R)-epichlorohydrin was obtained with 35 % yield and 99 % enantiomeric excess. The immobilized EH showed good operational stability and even after six reactions, it retained >85 % of the initial activity. CONCLUSION: The operational stability and recyclability of immobilized EH on an EDA functionalized epoxy supports demonstrated its potential for producing (R) epichlorohydrin. PMID- 27379655 TI - Circulating insulin-like growth factor 1 and insulin-like growth factor binding protein-3 level in Alzheimer's disease: a meta-analysis. AB - It has been reported that the associations between circulating insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP 3) and Alzheimer's disease (AD) are controversial. Thus, present meta-analysis was carried out to confirm the probable associations. We searched "PubMed", "Springer" and "Medline" databases using the term ("insulin-like growth factor-1" or "IGF-1" or "insulin-like growth factor binding protein-3" or "IGFBP-3") and ("Alzheimer's disease") until April 2016. Furthermore, standard mean differences (SMDs) were calculated. A total of seven reports involving 1342 percipients were pooled. SMDs were -0.25 (P = 0.22) and -0.33 (P = 0.08) for IGF-1 and IGFBP-3, respectively. Furthermore, the circulating IGF-1 levels in AD patients were lower than controls when studies with the difference of mean age <=1 year (SMD -0.57, P = 0.007) or 2 years (SMD -0.58, P = 0.02) or difference of mean MMSE scores <=10 scores (SMD -0.94, P < 0.00001), or studies from Europe (SMD -0.89, P < 0.00001) were excluded. In addition, the circulating IGFBP-3 levels in AD patients were lower than controls when studies with the difference of mean age <=2 years (SMD 0.62, P = 0.006) or difference of mean MMSE scores <=6 scores (SMD -0.48, P = 0.0004), 7 scores (SMD -0.58, P = 0.02), or 8 scores (SMD -0.80, P = 0.03) were excluded. Even though no significant difference of circulating IGF-1 and IGFBP-3 levels in AD patients comparing with controls was found in present meta-analysis, the current study provided the evidence that the circulating IGF-1 and IGFBP-3 level in AD patients were influenced by the difference of mean age as well as MMSE scores. Furthermore, circulating IGFBP-3 levels in AD patients may be decreased earlier than IGF-1. PMID- 27379656 TI - Vessel floating sign by echocardiography. PMID- 27379654 TI - A Randomized Trial of Iloperidone for Prevention of Relapse in Schizophrenia: The REPRIEVE Study. AB - BACKGROUND: The purpose of this study was to evaluate the safety and effectiveness of iloperidone for the prevention of relapse in schizophrenia. METHODS: Study subjects were adults with schizophrenia who started on oral open label iloperidone titrated to an initial target dose of 12 mg/day (6 mg twice daily) and then stabilized on a flexible-dose iloperidone regimen (range 8-24 mg/day) for up to 24 weeks. Subjects meeting stabilization criteria then entered the relapse-prevention phase and were randomized 1:1 in a double-blind fashion to continue with iloperidone or placebo withdrawal for up to 26 weeks or until meeting relapse or other withdrawal criteria. RESULTS: A total of 303 subjects were randomized to the relapse-prevention phase; 153 continued to receive iloperidone, and 150 were withdrawn to placebo. The modal total daily dose for iloperidone in all phases of the study was 12 mg/day. The pre-defined unblinded interim analysis upon reaching 68 relapse events confirmed the hypothesis that iloperidone (n = 97) was more effective than placebo (n = 96) in preventing relapse events, and the trial was stopped early. The estimated relapse rates were 63.4 % (Kaplan-Meier [KM] estimate) for placebo compared with 20.4 % (KM estimate) for those continuing to receive iloperidone (log rank test: p < 0.0001). The mean time to relapse was 71 days for placebo and 139 days for iloperidone (hazard ratio 4.7; 95 % confidence interval 2.7-8.3; p < 0.0001). The safety profile observed in previous short-term studies was also reaffirmed in this maintenance treatment setting. The most common treatment-emergent adverse events (TEAEs) in the stabilization phase were dizziness (11.6 %), somnolence (8.3 %), and dry mouth (6.8 %). Rates of reported extrapyramidal disorder or akathisia during stabilization were 2.5 and 3.7 %, respectively. CONCLUSIONS: Flexible dosing of iloperidone for maintenance-phase therapy, with a modal dose of 12 mg/day was effective in preventing relapse in subjects previously stabilized on iloperidone. The adverse event profile for iloperidone was consistent with other studies, and the low extrapyramidal symptom and akathisia burden during stabilization was sustained during the course of the study. ClinicalTrials.gov identifier: NCT01291511. PMID- 27379657 TI - [Not Available]. PMID- 27379658 TI - Thoracic Outlet Syndrome in the Overhead Athlete: A Report of 2 Cases of Subclavius Posticus Muscle. AB - Subclavius posticus muscle is a supernumerary anatomical variation of the subclavius muscle. The aim of this study was to show the possible contribution of the posticus muscle in the development of unilateral thoracic outlet syndrome (TOS) in overhead athletes, presenting hypertrophy of the dominant arm due to their sport activity. Reported here are 2 young overhead athletes complaining pain, paresthesia, weakness in the dominant upper limb, although presenting none of the main shoulder and neurological disorders. After developing subclavian vein thrombosis, TOS was suspected and finally diagnosed by dynamic magnetic resonance angiography, which also showed bilateral subclavius posticus muscle in both patients. Despite bilateral subclavius posticus, TOS was only evident in the dominant limb in which the association of hypertrophy of lateral cervical muscles, resulting from the overhead sport activity, to the subclavius posticus likely led to a significant reduction of the upper thoracic outlet space. PMID- 27379659 TI - Heart Rate Variability of Athletes Across Concussion Recovery Milestones: A Preliminary Study. AB - OBJECTIVE: To assess heart rate variability (HRV) in athletes with concussion across three phases of recovery. DESIGN: A prospective matched control group design included the collection of HRV and symptoms measured by the Rivermead Post Concussion Questionnaire. These measures were taken at 3 phases of recovery [(1) symptomatic; (2). asymptomatic; and (3) one-week after return-to-play (RTP)]. The same protocol was completed by noninjured athletes. SETTING: Interuniversity sports teams at a single institution. PARTICIPANTS: 11 athletes, across 7 sports, diagnosed with concussion, and 11 matched-athlete controls volunteered for the study. INTERVENTION: Physician diagnosed concussion and a sitting to standing protocol for HRV monitoring. MAIN OUTCOME MEASURES: The frequency, time, and nonlinear domains of HRV were assessed along with the absolute difference between sitting and standing for each. RESULTS: A 2 x 3 (group x phase) repeated-measures analysis of variance revealed significant interactions for sitting High Frequency (HF) norm, sitting Low Frequency (LF) norm, the difference between sitting and standing HF norm, and difference between sitting and standing LF norm. Acutely, athletes with concussion displayed increased LF norm and decreased HF norm while sitting and a decreased change in their HF and LF norm measures between sitting and standing. A significant group effect for sample entropy when standing was detected, with the concussed group displaying decreased values compared with the matched controls. CONCLUSIONS: Athletes with concussion displayed autonomic dysfunction in some measures of HRV that persisted beyond RTP and were related to a previous history of concussion. PMID- 27379661 TI - Comparison of Different Physical Activity Measurement Methods in Adults Aged 45 to 64 Years Under Free-Living Conditions. AB - OBJECTIVE: To compare physical activity (PA) measured by 4 methods in adults under free-living conditions in relation to selected demographic and anthropometric variables. DESIGN: Cohort study. SETTING: Department of Sports Medicine. PARTICIPANTS: Clinically healthy men (81) and women (69) aged 45 to 64 years. INTERVENTIONS: Physical activity monitoring for 7 consecutive days under free-living conditions by pedometer (P) and accelerometer (A) simultaneously and PA questionnaires: International Physical Activity Questionnaire (IPAQ) and Seven Day Physical Activity Questionnaire Recall (SDPAR) completed after the 7-day PA. MAIN OUTCOME MEASURES: Comparison of PA measured by pedometer, IPAQ, and SDPAR with accelerometer with regard to age, body mass, gender, and obesity type. RESULTS: Total energy expenditure (EE) by IPAQ was higher than A (P < 0.001) in both groups regardless of age, body mass, or obesity type. Mean EE value by P was greater than A (P < 0.001) in central-obesity males and lower than A (P < 0.001) in central-obesity females. There were differences in step counts in women, unnoticed in men. SDPAR overestimated total EE in gynoid-obesity males and in central-obesity females compared with A. Ninety-five percent CI was the largest around IPAQ compared with P and SDPAR, with SDPAR showing the best agreement with A. CONCLUSIONS: Body mass and obesity type influenced PA measurements. To monitor PA, it is recommended to use pedometer in normal bodyweight and overweight groups while accelerometer is advisable in obese subjects. A combined approach of objective and subjective PA monitoring tools is preferable. PMID- 27379660 TI - Sex Differences in Vestibular/Ocular and Neurocognitive Outcomes After Sport Related Concussion. AB - OBJECTIVE: To examine sex differences in vestibular and oculomotor symptoms and impairment in athletes with sport-related concussion (SRC). The secondary purpose was to replicate previously reported sex differences in total concussion symptoms, and performance on neurocognitive and balance testing. DESIGN: Prospective cross-sectional study of consecutively enrolled clinic patients within 21 days of a SRC. SETTING: Specialty Concussion Clinic. PARTICIPANTS: Included male (n = 36) and female (n = 28) athletes ages 9 to 18 years. INTERVENTIONS: Vestibular symptoms and impairment was measured with the Vestibular/Ocular Motor Screening (VOMS). Participants completed the Immediate Post-concussion Assessment and Cognitive Test (ImPACT), Post-concussion Symptom Scale (PCSS), and Balance Error Scoring System (BESS). MAIN OUTCOMES MEASURES: Sex differences on clinical measures. RESULTS: Females had higher PCSS scores (P = 0.01) and greater VOMS vestibular ocular reflex (VOR) score (P = 0.01) compared with males. There were no sex differences on BESS or ImPACT. Total PCSS scores together with female sex accounted for 45% of the variance in VOR scores. CONCLUSIONS: Findings suggest higher VOR scores after SRC in female compared with male athletes. Findings did not extend to other components of the VOMS tool suggesting that sex differences may be specific to certain types of vestibular impairment after SRC. Additional research on the clinical significance of the current findings is needed. PMID- 27379663 TI - [Not Available]. PMID- 27379662 TI - Study on the Mechanism of Interaction between Phthalate Acid Esters and Bovine Hemoglobin. AB - Phthalate acid esters (PAEs) are widely used in plastic products as a series of chemical softeners. However, PAEs, which now exist in many environmental media such as the atmosphere, water, and soil, have been shown to be environmental endocrine disruptors. Hemoglobin is a functional protein that carries oxygen in the red blood cells of animals. This study aims at revealing the interactions between bovine hemoglobin (BHb) and PAEs using spectroscopic and molecular modeling methods. The results indicate that the selected representative PAEs dimethyl phthalate (DMP), diethyl phthalate (DEP), and dibutyl phthalate (DBP) can interact with BHb to form BHb-PAE complexes with one binding site, mainly relying on hydrophobic forces, with the affinity order DMP > DEP > DBP, opposite to the order of side-chain length. The binding of PAEs can cause conformational and micro-environmental changes in BHb, which may affect the physiological functions of Hb. Furthermore, molecular docking was applied to define the specific binding sites, the results of which show that all the three PAEs can bind into the central cavity of BHb. The study contributes to expound the toxic mechanism of PAEs in vivo from the point of hematological toxicology. PMID- 27379664 TI - [Not Available]. AB - Jaundice is a symptom with a multitude of possible causes. These can be divided up into primary diseases of bilirubin metabolism, secondary hyperbilirubinemia in patients with liver disease, and diseases with bile duct occlusion.The major objective of the examination must be to exclude those causes that represent an acute danger to the patient, in particular cholangitis or cholecystitis. Symptoms that should cause alarm bells to ring include abdominal pain, fever and chills. When obtaining the patient's anamnesis, particular attention must be paid to lithiasis and previous operations. Laboratory findings of elevated alkaline phosphatase and gamma-GT indicate the presence of cholestasis. If an extrahepatic obstruction is suspected, ultrasonography of the upper abdomen is required. PMID- 27379665 TI - [Not Available]. PMID- 27379666 TI - Iodine(III)-Mediated Selective Intermolecular C-H Amination for the Chemical Diversification of Tryptamines. AB - Defined hypervalent iodine reagents of the general structure PhI[N(SO2R)(SO2R')]2 promote the selective direct C-H-amination of the indole core of various tryptamines. Starting from a general C2-amination strategy, subsequent transformations enable a variety of site-selective functionalizations, which proceed with noteworthy high chemoselectivity and provide an overall access to structurally diversified products. PMID- 27379667 TI - Current and cumulative night shift work and subclinical atherosclerosis: results of the Gutenberg Health Study. AB - PURPOSE: The study examines the association between exposure to current and cumulative night shift work and subclinical parameters of atherosclerosis. METHODS: Participants of a population-based cohort study (the Gutenberg Health Study, N = 15,010) aged 35-64 years were examined at baseline (2007-2012). Investigations included measurements of arterial stiffness, vascular function [reactive hyperaemia (RH) index], and intima media thickness (IMT). Also, a complete job history (including up to 15 periods), occupational exposures, a variety of lifestyle, and dispositional variables were enquired. RESULTS: Night shift work was performed by 1071 out of 8065 currently employed individuals. The strongest association after adjustment for age, sex, job complexity level, being a manager, overtime work, and noise appeared for more than 660 night shifts within the last 10 years and a significantly increased arterial stiffness of 0.33 m/s. This reflects a 4 % flow velocity increase for individuals with more than 660 night shifts compared to non-night workers. Regarding the entire professional life, night shift workers showed a significantly decreased vascular function by 0.054 RH index points by using the same adjustment. IMT values did not differ statistically from non-night workers. Lifestyle and dispositional factors showed an influence on all used subclinical atherosclerosis parameters. CONCLUSIONS: The cross-sectional results demonstrate an association between night work and detrimental changes in the atherosclerotic process. The association is more pronounced with more years in night shift and is partly explained by lifestyle and dispositional factors. Longitudinal analyses are necessary to confirm the results. PMID- 27379668 TI - Family and Community Predictors of Comorbid Language, Socioemotional and Behavior Problems at School Entry. AB - OBJECTIVES: To identify the prevalence and family and community-level predictors of comorbid speech-language difficulties and socioemotional and behavioral (SEB) difficulties across a population of children at school entry. METHODS: The School Entry Health Questionnaire is a parent survey of children's health and wellbeing, completed by all children starting school in Victoria, Australia (N = 53256). It includes parental report of speech-language difficulties, the Strengths and Difficulties Questionnaire (behavior), and numerous family and community variables. Following univariate analysis, family and community risk characteristics were entered into a multinomial logistic regression model to identify the associated relative risk of comorbid speech/language and SEB needs. The influence of experiencing multiple risk factors was also examined. RESULTS: 20.4% (n = 10,868) began school with either speech-language or SEB difficulties, with 3.1% (n = 1670) experiencing comorbid needs. Five factors predicted comorbidity: the child having witnessed violence; a history of parent mental illness; living in more deprived communities; and the educational attainment of each parent (independently). The relative risk of comorbidity was 6.1 (95% Confidence Interval: 3.9, 9.7) when a child experienced four or more risk factors, compared to those with no risk factors. CONCLUSIONS: The risk of comorbidity in early childhood is associated with a range of family and community factors, and elevated by the presence of multiple factors. Children growing up in families experiencing multiple, complex needs are therefore at heightened risk of the early development of difficulties likely to impact upon schooling. Early identification of these children offers opportunities for appropriate and timely health and education intervention. PMID- 27379669 TI - Placental endoplasmic reticulum stress and acidosis: relevant aspects in gestational diabetes. AB - In this issue, Yung and colleagues (doi: 10.1007/s00125-016-4040-2 ) report endoplasmic reticulum stress in the placenta of patients with gestational diabetes mellitus. With the use of a trophoblast-like cell line, these authors identify putative mechanisms involved in, and treatments to prevent the induction of endoplasmic reticulum stress. Here, the relevance and possible implications of these findings and areas for further research are discussed. PMID- 27379670 TI - Single-stage medial open reduction and Pemberton acetabuloplasty in developmental dysplasia of the hip. AB - In this study, we aimed to evaluate the long-term clinical and radiological results of single-stage open reduction through a medial approach and Pemberton acetabuloplasty in developmental dysplasia of the hip. We treated 32 hips (22 patients) with developmental dysplasia by a single-stage open reduction through Ferguson's medial approach and Pemberton acetabuloplasty. The procedure was performed bilaterally in 10 patients. The mean age of the patients at the time of the operation was 19.8 months (16-24 months). The mean follow-up period was 10.9 years (7-19 years). Group I avascular necrosis according to the Kalamchi and MacEwen classification was observed in two hips and group II in one hip. Radiologically, 90.6% of the hips were classified as Severin class I and 9.4% of the hips were classified as Severin class II. At the latest follow-up, 30 hips were assessed clinically as excellent and two hips as good. No patient required subsequent surgery. We conclude that single-stage medial open reduction and Pemberton acetabuloplasty represent an effective method for developmental dysplasia of the hip in children older than 15 months of age. PMID- 27379671 TI - The management of residual acetabular dysplasia: updates and controversies. AB - Residual acetabular dysplasia is a frequent cause of secondary osteoarthritis of the hip and its management is still controversial. The aim of this review is to describe residual acetabular dysplasia, to estimate the age limit above which surgical management is needed, and to emphasize the role of assistive imaging in evaluating predictive parameters for future acetabular development. A decision making algorithm is presented. PMID- 27379673 TI - Consumption of Meals Prepared at Home and Risk of Type 2 Diabetes: An Analysis of Two Prospective Cohort Studies. AB - BACKGROUND: There has been a trend towards increased dining out in many countries. Consuming food prepared out of the home has been linked to poor diet quality, weight gain, and diabetes risk, but whether having meals prepared at home (MPAH) is associated with risk of type 2 diabetes (T2D) remains unknown. METHODS AND FINDINGS: We followed 58,051 women (from 1986 to 2012) and 41,676 men (from 1986 to 2010) in two prospective cohort studies of health professionals. Frequencies of consuming midday or evening MPAH were assessed at baseline and during follow-up. Incident T2D was identified through self-report and confirmed using a validated supplementary questionnaire. During 2.1 million person-years of follow-up, 9,356 T2D cases were documented. After adjusting for demographic, socioeconomic, and lifestyle factors, hazard ratios (HRs) and 95% confidence intervals (95% CIs) of T2D were 1 (reference), 0.93 (0.88-0.99), 0.96 (0.90 1.03), and 0.86 (0.81-0.91) for those eating 0-6, 7-8, 9-10, and 11-14 MPAH (p trend < 0.001) per week, respectively. Participants eating 5-7 midday MPAH had 9% lower T2D risk than those with 0-2 midday MPAH, and participants having 5-7 evening MPAH had 15% lower risk than those with 0-2 evening MPAH (both p-trend < 0.001). In the first 8 y of follow-up, women and men who consumed 11-14 MPAH per week had 0.34 kg (95% CI: 0.15-0.53; p < 0.001) and 1.23 kg (95% CI: 0.92-1.54) less weight gain than those with 0-6 MPAH, respectively. Among participants who were nonobese (body mass index [BMI] < 30 kg/m2) at baseline, pooled HR (95% CI) of developing obesity (BMI >= 30 kg/m2) was 0.86 (0.82-0.91; p-trend < 0.001) when extreme MPAH groups (11-14 MPAH versus 0-6 MPAH) were compared. When midday and evening MPAH were analyzed separately, HRs comparing extreme groups (5-7 MPAH versus 0-2 MPAH) were 0.93 (95% CI: 0.89-0.97, p-trend = 0.003) for midday MPAH and 0.76 (95% CI: 0.70-0.83; p-trend < 0.001) for evening MPAH. Further adjusting for BMI during follow-up attenuated the association between MPAH and T2D risk: the HR (95% CI) for participants with 11-14 MPAH was 0.95 (0.89-1.01, p-trend = 0.13). The main limitations of our study were that it lacked assessments on individual foods constituting the MPAH and that the findings were limited to health professionals with a relatively homogeneous socioeconomic status. CONCLUSIONS: In two large prospective cohort studies, frequent consumption of MPAH is associated with a lower risk of developing T2D, and this association is partly attributable to less weight gain linked with this dining behavior. PMID- 27379675 TI - State of the Society. PMID- 27379674 TI - Infusion Standards: A Document Without Borders. PMID- 27379676 TI - 2015 INS Financial Report. PMID- 27379677 TI - Presidential Address. PMID- 27379678 TI - Influencing Patient Satisfaction Scores: Prospective One-Arm Study of a Novel Intravenous Catheter System With Retractable Coiled-Tip Guidewire Compared With Published Literature for Conventional Peripheral Intravenous Catheters. AB - With potential hospital reimbursement centered on patient satisfaction, limiting the number of invasive peripheral venipunctures may increase Press Ganey satisfaction scores. A prospective study compared published outcomes with conventional intravenous (IV) catheters against results using a newly designed IV catheter with a retractable, coiled-tip guidewire. The objectives were to determine whether successful first-attempt and IV complication rates might be altered using the new technology. In a small community hospital-based study of 95 patients, first-attempt success, complications, dwell time, and patient satisfaction results with the new technology scored significantly better, from insertion to removal, than published outcomes with conventional catheters. PMID- 27379672 TI - Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants. AB - Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs). We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33). We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s). PMID- 27379679 TI - Catheter Securement Systems for Peripherally Inserted and Nontunneled Central Vascular Access Devices: Clinical Evaluation of a Novel Sutureless Device. AB - Sutureless catheter securement systems are intended to eliminate risks associated with sutures. The clinical acceptability of a novel system was investigated compared with the current method of securement for peripherally inserted central catheters (19 facilities using StatLock or sutures) or nontunneled central vascular access devices (3 facilities using StatLock or sutures or HubGuard + Sorbaview Shield). More than 94% of respondents rated the novel system as same, better, or much better than their current product. More than 82% of respondents were willing to replace their current system with the new one. PMID- 27379680 TI - Evolution of the Treatments for Hemophilia. AB - Although hemophilia has been recognized for centuries as an inherited disorder primarily affecting males, advances in treatments have been very recent. Initial availability of plasma-derived therapies offered significant improvements in morbidity and mortality, but the transmission of viruses quickly negated the benefit of early factor replacement products. After developing successful viral inactivation methods and subsequently developing recombinant technology, the manufacturing of factor concentrates became much safer. Access to safer factor products allowed for a shift from the treatment of bleeds to prevention, called prophylaxis. Although dosing and interval vary, prevention of joint disease is now a realistic goal. Unfortunately, despite advances in the safety of therapy, some patients are unable to use factor replacement products because they develop antibodies, known as inhibitors. Eradication of inhibitors is possible in the majority of patients, but it is expensive and takes time. Management of acute bleeding may require significantly higher doses of factor replacement or the use of a bypassing agent. As a result, patients with inhibitors are at increased risk for sequelae, including joint disease, life-threatening bleeding, infectious complications with central vascular access devices, and thrombotic complications. PMID- 27379681 TI - Taking Another View: How Nurses Perceive Infusion Pumps as Demanding for Both Themselves and Their Patients. AB - Based on an organization theory perspective, this study proposes that nurses not only consider how infusion pumps place demands on themselves but also consider how infusion pumps place demands on patients. Results from a sample of nurses in a large, public authority, nonprofit teaching hospital located in the midwestern United States indicate that "demanding formalization for nurses" and "demanding formalization for patients" are 2 empirically distinct constructs. Demanding formalization for patients was a stronger predictor of infusion pump-related attitudes, in addition to trust and pay satisfaction. Demanding formalization for nurses was a stronger predictor of job satisfaction, turnover intention, and burnout. PMID- 27379682 TI - Medication Errors Involving the Intravenous Administration Route: Characteristics of Voluntarily Reported Medication Errors. AB - Characteristics of medication errors involving the intravenous (IV) route of administration were analyzed in reports from 1995 to 2013. This was accomplished through a voluntary medication error reporting program. A retrospective case study design analyzed reports by practitioners or consumers on IV-associated medication errors (N = 975) affecting patients. Patterns in error accounts reflected cultural changes in health care organizations. Equipment, labeling, incorrect route of administration, types of errors, patient outcomes, and causal agents represented major codes. Results point to health care provider and consumer knowledge, the need for ongoing education of nursing staff, and interdisciplinary strategies for preventing IV-associated medication errors. PMID- 27379683 TI - Structure of Exogenous Gene Integration and Event-Specific Detection in the Glyphosate-Tolerant Transgenic Cotton Line BG2-7. AB - In this study, the flanking sequence of an inserted fragment conferring glyphosate tolerance on transgenic cotton line BG2-7 was analyzed by thermal asymmetric interlaced polymerase chain reaction (TAIL-PCR) and standard PCR. The results showed apparent insertion of the exogenous gene into chromosome D10 of the Gossypium hirsutum L. genome, as the left and right borders of the inserted fragment are nucleotides 61,962,952 and 61,962,921 of chromosome D10, respectively. In addition, a 31-bp cotton microsatellite sequence was noted between the genome sequence and the 5' end of the exogenous gene. In total, 84 and 298 bp were deleted from the left and right borders of the exogenous gene, respectively, with 30 bp deleted from the cotton chromosome at the insertion site. According to the flanking sequence obtained, several pairs of event specific detection primers were designed to amplify sequence between the 5' end of the exogenous gene and the cotton genome junction region as well as between the 3' end and the cotton genome junction region. Based on screening tests, the 5'-end primers GTCATAACGTGACTCCCTTAATTCTCC/CCTATTACACGGCTATGC and 3'-end primers TCCTTTCGCTTTCTTCCCTT/ACACTTACATGGCGTCTTCT were used to detect the respective BG2 7 event-specific primers. The limit of detection of the former primers reached 44 copies, and that of the latter primers reached 88 copies. The results of this study provide useful data for assessment of BG2-7 safety and for accelerating its industrialization. PMID- 27379685 TI - Activation of human bitter taste receptors by polymethoxylated flavonoids. AB - Tangeretin and nobiletin are polymethoxylated flavonoids in citrus peel. Both tangeretin and nobiletin are bitter; however, their bitterness has not been evaluated using human bitter taste receptors (hTAS2Rs). We screened 25 kinds of hTAS2Rs and found that hTAS2R14 and hTAS2R46 received both compounds. PMID- 27379686 TI - Effects and Location of Coplanar and Noncoplanar PCB in a Lipid Bilayer: A Solid State NMR Study. AB - Coplanar and noncoplanar polychlorinated biphenyls (PCBs) are known to have different routes and degree of toxicity. Here, the effects of noncoplanar PCB 52 and coplanar PCB 77 present at 2 mol % in a model system consisting of POPC liposomes (50% hydrated) are investigated by solid-state (13)C and (31)P NMR at 298 K. Both PCBs intercalate horizontally in the outer part of the bilayer, near the segments of the acyl chain close to the glycerol group. Despite similar membrane locations, the coplanar PCB 77 shows little effect on the bilayer properties overall, except for the four nearest neighboring lipids, while the effect of PCB 52 is more dramatic. The first ~2 layers of lipids around each PCB 52 in the bilayer form a high fluidity lamellar phase, whereas lipids beyond these layers form a lamellar phase with a slight increase in fluidity compared to a bilayer without PCB 52. Further, a third high mobility domain is observed. The explanation for this is the interference of several high fluidity lamellar phases caused by interactions of PCB 52 molecules in different leaflets of the model bilayer. This causes formation of high curvature toroidal region in the bilayer and might induce formation of channels. PMID- 27379684 TI - Prolonged Treatment with Propofol Transiently Impairs Proliferation but Not Survival of Rat Neural Progenitor Cells In Vitro. AB - Neurocognitive dysfunction is common in survivors of intensive care. Prolonged sedation has been implicated but the mechanisms are unclear. Neurogenesis continues into adulthood and is implicated in learning. The neural progenitor cells (NPC) that drive neurogenesis have receptors for the major classes of sedatives used clinically, suggesting that interruption of neurogenesis may partly contribute to cognitive decline in ICU survivors. Using an in vitro system, we tested the hypothesis that prolonged exposure to propofol concentration- and duration-dependently kills or markedly decreases the proliferation of NPCs. NPCs isolated from embryonic day 14 Sprague-Dawley rat pups were exposed to 0, 2.5, or 5.0 MUg/mL of propofol, concentrations consistent with deep clinical anesthesia, for either 4 or 24 hours. Cells were assayed for cell death and proliferation either immediately following propofol exposure or 24 hours later. NPC death and apoptosis were measured by propidium iodine staining and cleaved caspase-3 immunocytochemistry, respectively, while proliferation was measured by EdU incorporation. Staurosporine (1MUM for 6h) was used as a positive control for cell death. Cells were analyzed with unbiased high-throughput immunocytochemistry. There was no cell death at either concentration of propofol or duration of exposure. Neither concentration of propofol impaired NPC proliferation when exposure lasted 4 h, but when exposure lasted 24 h, propofol had an anti-proliferative effect at both concentrations (P < 0.0001, propofol vs. control). However, this effect was transient; proliferation returned to baseline 24 h after discontinuation of propofol (P = 0.37, propofol vs. control). The transient but reversible suppression of NPC proliferation, absence of cytotoxicity, and negligible effect on the neural stem cell pool pool suggest that propofol, even in concentrations used for clinical anesthesia, has limited impact on neural progenitor cell biology. PMID- 27379689 TI - Letter From the Editor: The pedant and the scoundrel. PMID- 27379687 TI - Malpighian Tubule Cells in Overwintering Cave Crickets Troglophilus cavicola (Kollar, 1833) and T. neglectus Krauss, 1879 (Rhaphidophoridae, Ensifera). AB - During winter, cave cricket larvae undergo dormancy in subterranean habitats; this dormancy is termed diapause in second year Troglophilus cavicola larvae because they mature during this time, and termed quiescence in T. neglectus, because they mature after dormancy. Here we used electron microscopy to analyze ultrastructural changes in the epithelial cells in the Malpighian tubules (MTs) of T. cavicola during diapause, in order to compare them with previous findings on T. neglectus. Moreover, the autophagosomes were studied with immunofluorescence microscopy in both species. Although the basic ultrastructure of the cells was similar, specific differences appeared during overwintering. During this natural starvation period, the nucleus, rER, the Golgi apparatus and mitochondria did not show structural changes, and the spherites were exploited. The abundances of autophagic structures in both species increased during overwintering. At the beginning of overwintering, in both species and sexes, the rates of cells with autophagic structures (phagophores, autophagosomes, autolysosomes and residual bodies) were low, while their rates increased gradually towards the end of overwintering. Between sexes, in T. cavicola significant differences were found in the autophagosome abundances in the middle and at the end, and in T. neglectus at the end of overwintering. Females showed higher rates of autophagic cells than males, and these were more abundant in T. cavicola. Thus, autophagic processes in the MT epithelial cells induced by starvation are mostly parallel in diapausing T. cavicola and quiescent T. neglectus, but more intensive in diapausing females. PMID- 27379688 TI - Image-guided adaptive brachytherapy in locally advanced cervical cancer: recent advances and perspectives. AB - PURPOSE OF REVIEW: Image-guided adaptive brachytherapy (IGABT) is a high precision radiation that allows defining accurately treatment targets and optimizing their coverage whereas sparing efficiently the surrounding organs at risk. Ten years ago, in a will of harmonizing the reporting of brachytherapy, the Groupe Europeen de Curietherapie - European Society for Radiation Oncology (GEC ESTRO) published recommendations on target definitions and dosimetric parameters. During the last years, clinical and dosimetric studies supporting their relevance led the International Commission on Radiation Units and Measurements to propose a report on prescribing and reporting. This review aims to highlight the recent advances in IGABT and its future developments. RECENT FINDINGS: Clinical evidence demonstrating the superiority of IGABT over radiographs-based brachytherapy is accumulating. In parallel, dose-volume effects have been established between dose volume parameters and tumor response or the occurrence of late radiation morbidity. Preliminary studies indicate that planning aims could be adapted to clinical situations and cofactors. The first publications from the large studies led by the GEC-ESTRO enforce these findings. SUMMARY: A trend emerges toward a personalization of treatment with the adaptation of planning aims to prognostic features and the development of individualized applicators. Image-guidance modalities are developed with a better use of MRI or conversely the use of more accessible modalities such as transrectal ultrasound. PMID- 27379690 TI - FDA regulation of laboratory-developed tests. PMID- 27379691 TI - Current understanding of resistance to abiraterone and enzalutamide in advanced prostate cancer. PMID- 27379692 TI - Preventive strategies for invasive Aspergillus in acute myelogenous leukemia. PMID- 27379693 TI - What should standard frontline therapy be in older patients with chronic lymphocytic leukemia? Ibrutinib should be standard frontline therapy. PMID- 27379694 TI - What should standard frontline therapy be in older patients with chronic lymphocytic leukemia? Chemoimmunotherapy should be standard frontline therapy. PMID- 27379696 TI - HSP90 inhibitors in lung cancer: promise still unfulfilled. AB - Despite recent advances in the treatment of lung cancer, non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths in the United States and worldwide, with a 5-year survival rate of less than 17%. Analysis of the molecular drivers of NSCLC led to the recognition that NSCLC is a collection of distinct, molecularly driven neoplasms. Several subsets of NSCLC with clinical relevance to targeted therapies are defined based on alterations in EGFR, ALK, and other key oncogenic drivers. However, for many oncogenic drivers-such as mutant KRAS-targeted therapies are lacking. Heat shock protein 90 (HSP90) is an adenosine triphosphate (ATP)-dependent molecular chaperone that is critically required for the stability of its clientele, many of which are driver oncoproteins. Therefore, HSP90 inhibitors could prove to be an effective and alternate approach to treat patients with NSCLC that has a specific molecular background or that has acquired resistance to other drugs. Over the last 2 decades, several HSP90 inhibitors have been developed that produced promising preclinical and clinical results. The quest is far from over, however. In this review, we discuss the development and the preclinical and clinical profiles of some of the HSP90 inhibitors that may help to improve the targeted treatment of NSCLC. PMID- 27379697 TI - Dual-Energy Computed Tomography for the Characterization of Intracranial Hemorrhage and Calcification: A Systematic Approach in a Phantom System. AB - OBJECTIVE: The aim of this study was to develop a diagnostic framework for distinguishing calcific from hemorrhagic cerebral lesions using dual-energy computed tomography (DECT) in an anthropomorphic phantom system. MATERIALS AND METHODS: An anthropomorphic phantom was designed to mimic the CT imaging characteristics of the human head. Cylindrical lesion models containing either calcium or iron, mimicking calcification or hemorrhage, respectively, were developed to exhibit matching, and therefore indistinguishable, single-energy CT (SECT) attenuation values from 40 to 100 HU. These lesion models were fabricated at 0.5, 1, and 1.5 cm in diameter and positioned in simulated cerebrum and skull base locations within the anthropomorphic phantom. All lesion sizes were modeled in the cerebrum, while only 1.5-cm lesions were modeled in the skull base. Images were acquired using a GE 750HD CT scanner and an expansive dual-energy protocol that covered variations in dose (36.7-132.6 mGy CTDIvol, n = 12), image thickness (0.625-5 mm, n = 4), and reconstruction filter (soft, standard, detail, n = 3) for a total of 144 unique technique combinations. Images representing each technique combination were reconstructed into water and calcium material density images, as well as a monoenergetic image chosen to mimic the attenuation of a 120 kVp SECT scan. A true single-energy routine brain protocol was also included for verification of lesion SECT attenuation. Points representing the 3 dual-energy reconstructions were plotted into a 3-dimensional space (water [milligram/milliliter], calcium [milligram/milliliter], monoenergetic Hounsfield unit as x, y, and z axes, respectively), and the distribution of points analyzed using 2 approaches: support vector machines and a simple geometric bisector (GB). Each analysis yielded a plane of optimal differentiation between the calcification and hemorrhage lesion model distributions. By comparing the predicted lesion composition to the known lesion composition, we identified the optimal combination of CTDIvol, image thickness, and reconstruction filter to maximize differentiation between the lesion model types. To validate these results, a new set of hemorrhage and calcification lesion models were created, scanned in a blinded fashion, and prospectively classified using the planes of differentiation derived from support vector machine and GB methods. RESULTS: Accuracy of differentiation improved with increasing dose (CTDIvol) and image thickness. Reconstruction filter had no effect on the accuracy of differentiation. Using an optimized protocol consisting of the maximum CTDIvol of 132.6 mGy, 5-mm-thick images, and a standard filter, hemorrhagic and calcific lesion models with equal SECT attenuation (Hounsfield unit) were differentiated with over 90% accuracy down to 70 HU for skull base lesions of 1.5 cm, and down to 100 HU, 60 HU, and 60 HU for cerebrum lesions of 0.5, 1.0, and 1.5 cm, respectively. The analytic method that yielded the best results was a simple GB plane through the 3-dimensional DECT space. In the validation study, 96% of unknown lesions were correctly classified across all lesion sizes and locations investigated. CONCLUSIONS: We define the optimal scan parameters and expected limitations for the accurate classification of hemorrhagic versus calcific cerebral lesions in an anthropomorphic phantom with DECT. Although our proposed DECT protocol represents an increase in dose compared with routine brain CT, this method is intended as a specialized evaluation of potential brain hemorrhage and is thus counterbalanced by increased diagnostic benefit. This work provides justification for the application of this technique in human clinical trials. PMID- 27379699 TI - Model-Based Characterization of the Transpulmonary Circulation by Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Heart Failure and Healthy Volunteers. AB - OBJECTIVES: Novel quantitative measures of transpulmonary circulation status may allow the improvement of heart failure (HF) patient management. In this work, we propose a method for the assessment of the transpulmonary circulation using measurements from indicator time intensity curves, derived from dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) series. The derived indicator dilution parameters in healthy volunteers (HVs) and HF patients were compared, and repeatability was assessed. Furthermore, we compared the parameters derived using the proposed method with standard measures of cardiovascular function, such as left ventricular (LV) volumes and ejection fraction. MATERIALS AND METHODS: In total, 19 HVs and 33 HF patients underwent a DCE-MRI scan on a 1.5 T MRI scanner using a T1-weighted spoiled gradient echo sequence. Image loops with 1 heartbeat temporal resolution were acquired in 4-chamber view during ventricular late diastole, after the injection of a 0.1-mmol gadoteriol bolus. In a subset of subjects (8 HFs, 2 HVs), a second injection of a 0.3-mmol gadoteriol bolus was performed with the same imaging settings. The study was approved by the local institutional review board.Indicator dilution curves were derived, averaging the MR signal within regions of interest in the right and left ventricle; parametric deconvolution was performed between the right and LV indicator dilution curves to identify the impulse response of the transpulmonary dilution system. The local density random walk model was used to parametrize the impulse response; pulmonary transit time (PTT) was defined as the mean transit time of the indicator. lambda, related to the Peclet number (ratio between convection and diffusion) for the dilution process, was also estimated. RESULTS: Pulmonary transit time was significantly prolonged in HF patients (8.70 +/- 1.87 seconds vs 6.68 +/- 1.89 seconds in HV, P < 0.005) and even stronger when normalized to subject heart rate (normalized PTT, 9.90 +/- 2.16 vs 7.11 +/- 2.17 in HV, dimensionless, P < 0.001). lambda was significantly smaller in HF patients (8.59 +/- 4.24 in HF vs 12.50 +/- 17.09 in HV, dimensionless, P < 0.005), indicating a longer tail for the impulse response. Pulmonary transit time correlated well with established cardiovascular parameters (LV end-diastolic volume index, r = 0.61, P < 0.0001; LV ejection fraction, r = -0.64, P < 0.0001). The measurement of indicator dilution parameters was repeatable (correlation between estimates based on the 2 repetitions for PTT: r = 0.94, P < 0.001, difference between 2 repetitions 0.01 +/- 0.60 second, for lambda: r = 0.74, P < 0.01, difference 0.69 +/- 4.39). CONCLUSIONS: Characterization of the transpulmonary circulation by DCE-MRI is feasible in HF patients and HVs. Significant differences are observed between indicator dilution parameters measured in HVs and HF patients; preliminary results suggest good repeatability for the proposed parameters. PMID- 27379698 TI - Magnetic Resonance Imaging Findings After Percutaneous Irreversible Electroporation of Liver Metastases: A Systematic Longitudinal Study. AB - OBJECTIVE: The aim of this study was to systematically investigate the course of magnetic resonance (MR) signal intensity (SI) changes that occur in noncirrhotic livers after irreversible electroporation (IRE) of liver metastases. METHODS: This study is an institutional review board-approved prospective longitudinal follow-up study on 27 patients with 37 liver metastases who underwent computed tomography-guided percutaneous IRE and a standardized follow-up protocol by serial hepatic MR imaging studies that consisted of a gadobutrol-enhanced dynamic series, axial T2-weighted (T2w) turbo spin echo, and diffusion-weighted imaging (b = 0/50/800), acquired before, within 2, and at 24 hours after IRE; at 1, 2, 4, 6, 8, and 12 weeks after IRE; and every 3 months thereafter for a follow-up of at least 12 months. RESULTS: The ablated target lesion remained visible within the ablation zone in 23 (62%) of 37 of cases for a mean time of 21 +/- 20 weeks (median, 12 weeks). The ablation zone appeared homogeneously hyperintense on T2w turbo spin echo images on the day of IRE in 37 of 37 cases. By 24 hours after IRE, the ablation zone inverted its SI in 35 of 37 cases to intermediately hypointense, with a rim of T2w bright SI that exhibited arterial phase enhancement; this persisted for 7 +/- 5 weeks (median, 4 weeks). The rim resolved in 35 (95%) of 37 cases within 3 months. The ablation zone increased slightly over the first 48 hours, then shrank progressively. Complete healing of the ablation zone was observed in 57% (21/37) after an average of 14 +/- 15 (median, 8 weeks).Average apparent diffusion coefficient values of the ablation zone decreased from 0.74 +/- 0.36 * 10 mm/s pre-IRE to 0.63 +/- 0.27 * 10 mm/s within the first 24 hours (P < 0.05), followed by a progressive normalization to 0.91 +/ 0.30 * 10 mm/s at 2 months. CONCLUSIONS: Knowledge of the broad spectrum of MR imaging findings after IRE is important to avoid diagnostic errors in the follow up of patients after IRE. PMID- 27379700 TI - Water in a Soft Confinement: Structure of Water in Amorphous Sorbitol. AB - The structure of water in 70 wt % sorbitol-30 wt % water mixture is investigated by wide-angle neutron scattering (WANS) as a function of temperature. WANS data are analyzed using empirical potential structure refinement to obtain the site site radial distribution functions (RDFs). Orientational structure of water is represented using OW-OW-OW triangles distributions and a tetrahedrality parameter, q, while water-water correlation function is used to estimate size of water clusters. Water structure in the sorbitol matrix is compared with that of water confined in nanopores of MCM41. The results indicate the existence of voids in the sorbitol matrix with the length scale of approximately 5 A, which are filled by water. At 298 K, positional water structure in these voids is similar to that of water in MCM41, whereas there is a difference in the tetrahedral (orientational) arrangement. Cooling to 213 K strengthens tetrahedrality, with the orientational order of water in sorbitol becoming similar to that of confined water in MCM41 at 210 K, whereas further cooling to 100 K does not introduce any additional changes in the tetrahedrality. The results obtained allow us to propose, for the first time, that such confinement of water in a sorbitol matrix is the main reason for the lack of ice formation in this system. PMID- 27379701 TI - Correction: Mortality, Rehospitalisation and Violent Crime in Forensic Psychiatric Patients Discharged from Hospital: Rates and Risk Factors. AB - [This corrects the article DOI: 10.1371/journal.pone.0155906.]. PMID- 27379702 TI - The Regulation of Dietary Supplements in Canada: Many Promises but Little Progress. AB - This article examines key issues concerning the regulation of dietary supplements in Canada. The article looks at problems related to both the composition of supplements and of marketing practices. It looks back to the situation around 1999, the year of the introduction of the new system for the regulation of supplements, and then assesses the situation now. The new system has failed to bring about the intended improvement in either the formulation of supplements or the level of honesty in their marketing. PMID- 27379703 TI - CEBPA mutation in a case of chronic myeloid leukemia presenting in myeloid blast crisis. PMID- 27379704 TI - Second prophylaxis of variceal bleeding in cirrhotic patients with a high HVPG. AB - OBJECTIVE: The hepatic venous pressure gradient (HVPG) could be used to stratify patients in different risk groups. No studies have reported the role of transjugular intrahepatic portosystemic shunt (TIPS) placement in a subgroup of patients with a high HVPG (>=20 mmHg) for secondary prophylaxis of variceal bleeding. This study was designed to evaluate the benefit of TIPS in cirrhotic patients with a high HVPG (>=20 mmHg) for rebleeding and survival. MATERIAL AND METHODS: We included 46 cirrhotic patients with a history of variceal bleeding and a high HVPG (>=20 mmHg) admitted to our hospital between January 2013 and June 2014 (TIPS group). Patients were matched by Child-Pugh scores to patients in our historical cohort hospitalized for prophylaxis of variceal rebleeding between April 2011 and December 2012 (propranolol + EVL group). The end points included time to significant rebleeding from portal hypertensive sources, 1-year survival, and time to the occurrence of hepatic encephalopathy (HE). RESULTS: The 1-year actuarial probability of remaining free of variceal rebleeding was significantly higher in the TIPS group than in the propranolol + EVL group (85% vs. 54%, p = 0.01). The 1-year survival rates were not different between the two groups (85% vs. 89%, p = 0.591). The 1-year actuarial probability of remaining free of HE was significantly lower in the TIPS group than in the propranolol + EVL group (67% vs. 91%, p = 0.003). CONCLUSIONS: TIPS was more effective than propranolol + EVL in preventing variceal rebleeding in cirrhotic patients with a high HVPG (>=20 mmHg). During the limited follow-up, survival was similar in the two groups. PMID- 27379705 TI - Further Evidence of a Cohort Effect in Bipolar Disorder: More Early Onsets and Family History of Psychiatric Illness in More Recent Epochs. AB - OBJECTIVE: Given that a cohort effect is rarely mentioned as one of the possible contributors to the increased incidence of childhood-onset bipolar disorder in the United States, we reexamined evidence for the phenomenon within our outpatient Bipolar Collaborative Network. METHODS: 968 outpatients (mean age, 41 years) with DSM bipolar disorder from 1995 to 2002 from 4 sites in the United States and 3 in the Netherlands and Germany (abbreviated as Europe) gave informed consent and provided detailed demographic, illness, and family history information on a patient questionnaire. Family history of bipolar disorder, depression, suicide attempt, alcohol abuse, substance abuse, and "other" illness was collected for each parent and the 4 grandparents. Age at onset and family history of illness burden were then assessed as a function of the age of the patient at network entry. RESULTS: Data for patients aged 35 years or older (n = 613) were included in the first analysis. Compared to older patients, those who were younger when they entered the network had an earlier age at onset of their bipolar disorder (r = 0.33, P < .001). Similarly, the youngest patients at entry (representing the most recent cohorts) had parents and grandparents with more psychiatric illness than patients born in earlier cohorts (n = 968). CONCLUSIONS: These preliminary data, taken with the substantial literature, suggest a cohort effect for earlier age at onset of bipolar disorder and greater burden of psychiatric disorders in 2 generations of direct progenitors of our patients. The resulting likely increase in severity of bipolar illness in future generations based on this earlier age at onset and increased familial loading, particularly in the United States, deserves focused clinical and public health attention and attempts at amelioration. PMID- 27379706 TI - Long-awaited pregnancy: intelligence and academic performance in offspring of infertile parents-a cohort study. AB - OBJECTIVE: To study whether fertility treatment, subfertility, or pregnancy planning are related to long-term intellectual development. DESIGN: Cohort study. SETTING: Not applicable. PATIENT(S): A total of 5,032 singletons born from 1990 to 1992 in the Aarhus Birth Cohort were followed up to a mean age of 19 years. These children were born as a result of fertility treatment (n = 210), had subfertile parents who took more than 12 months before conceiving naturally (n = 334), had fertile parents who conceived naturally within 12 months (n = 2,661), or had parents who reported the pregnancy as unplanned (n = 1,827). INTERVENTION(S): The children were followed up using questionnaires and information from Danish national registers. MAIN OUTCOME MEASURE(S): Parent reported school difficulties at ages 9-11 years, register-based school grades at ages 16, 17, and 19 years, and conscription intelligence test scores at age 19 years. RESULT(S): We found no evidence of school difficulties in childhood, impaired school performance in adolescence, or lower intelligence in young adulthood in multivariate analyses adjusted for parental age, educational level, maternal parity, before pregnancy body mass index (BMI), smoking and alcohol intake in pregnancy, cohabitation status, child gender, and age. CONCLUSION(S): In the longest follow-up of cognitive development of children conceived after fertility treatment or by subfertile parents conducted so far, this study did not show any association between pregnancy planning, subfertility, or fertility treatment and cognitive ability or academic performance. PMID- 27379707 TI - Adolescents' Daily Worries and Risky Behaviors: The Buffering Role of Support Seeking. AB - With worries and risky behaviors becoming more prominent in adolescence, this study investigated bidirectional temporal connections between these two important adolescent concerns, that is, whether change in one concern is linked to change in the other either within the same day or during the next day. We also tested whether the coping strategy of seeking support from family and friends moderated the link between worries and risky behaviors. For 10 days, an ethnically and racially diverse sample of adolescents (N = 103; M age = 18.0) reported on 26 common worries, 18 risky behaviors, and the impact of seeking support from others. Multilevel models showed that worries and risky behaviors covaried on the same day and that worries predicted next-day risky behavior for male but not female participants. In contrast, risky behaviors did not predict next-day worries. For adolescents reporting negative experiences of support seeking, worries led to next-day risky behaviors and risky behaviors led to next-day worries. Female adolescents' positive support-seeking experiences buffered the association between risky behaviors and next-day worries. These results were significant beyond any influence of daily negative mood or depressive and anxiety symptoms. The data demonstrate that worries and risky behaviors may be situational triggers for each other and highlight the importance, from intervention perspectives, of adolescents' communication of concerns to others. PMID- 27379708 TI - A Phase 2 Study of the Hsp90 Inhibitor AUY922 as Treatment for Patients with Refractory Gastrointestinal Stromal Tumors. AB - BACKGROUND: AUY922 is an inhibitor of heat shock protein 90 (Hsp90). Hsp90 inhibitors induce kit degradation in preclinical gastrointestinal stromal tumor (GIST) models. This trial was designed to determine the progression-free survival (PFS) of patients with GIST refractory to or intolerant of imatinib and sunitinib. METHODS: Eligible patients received AUY922 70 mg/mg(2) by intravenous (IV) infusion on days 1, 8, and 15 of 21-day cycles. Treatment continued until progression or unacceptable toxicity. RESULTS: Between December 2011 and January 2015, 25 patients were enrolled (median age, 63 years; 56% male) and received a median of 2 cycles (range: 1-12) of AUY922 treatment. Thirty-four patients were planned, but enrollment was stopped early due to slow accrual. Median PFS was 3.9 months (95% CI: 2.5, 5.3) and median OS was 8.5 months (95% CI: 5.2, 16.7). Radiographic response was evaluated in 21 patients; one patient achieved PR (4%) with another 15 having best response of stable disease (60%). The most common treatment-related adverse event was diarrhea (60% all grades). Reversible ocular toxicities that resulted in drug hold (24%) or reduction (8%) were also observed. CONCLUSION: AUY922 produced a median PFS which compares favorably to historical controls of placebo (6 weeks) for patients refractory to treatment with imatinib. While diarrhea and ocular toxicities were common, the majority of patients received treatment until disease progression. PMID- 27379709 TI - The Effect of Local Anesthetic Infiltration Around Nephrostomy Tract on Postoperative Pain Control after Percutaneous Nephrolithotomy: A Systematic Review and Meta-Analysis. AB - OBJECTIVES: To assess the safety and efficacy of local anesthetic infiltration around nephrostomy tract on postoperative pain control after percutaneous nephrolithotomy. METHODS: This systematic review was performed based on randomized clinic trials about local anesthetic infiltration around nephrostomy tract on postoperative pain control. The weighted mean difference (WMD), with their corresponding 95% CI, was calculated to compare continuous variables. RESULTS: Our results showed that the consumption of analgesic was less in the experimental group than in the control group (WMD -25.32, 95% CI -48.09 to -2.55, p = 0.003). There was no significant difference between the mean Visual Analog Scale (VAS) in the experimental group than the control group after 6 h while significantly lower after 24 h. The time of first analgesic demand was significantly longer in the experimental group (WMD 2.19, 95% CI 0.98-3.41). There was no significant difference between 2 groups in terms of operation time, hemoglobin (Hb) alteration, and hospital stay. CONCLUSION: Local anesthetic infiltration around nephrostomy tract had similar efficacy in the control group in terms of operation time, Hb alteration, and hospital stay, but offers some potential advantages in terms of analgesia requirement, the time of first analgesic demand, and VAS-24 h. However, good quality and large studies with long term follow-up are warranted for further research. PMID- 27379710 TI - The Aortic Isthmus: A Significant yet Underexplored Watershed of the Fetal Circulation. AB - The aortic isthmus (AoI) is a unique fetal watershed with a waveform reflecting its complex haemodynamic physiology. The systolic component represents left and right ventricular systolic ejection, and the diastolic component represents comparative downstream vascular impedance between the brachiocephalic and subdiaphragmatic fetal circulations. Several indices have been devised to quantify different components of the waveform, including the pulsatility index, resistance index, isthmic flow index, and recently the isthmic systolic index. There have been promising preliminary studies applying these indices to both cardiac (congenital) and extracardiac pathologies, including intrauterine growth restriction and twin-twin transfusion syndrome. However, the waveform's multifactorial origin has proven to be challenging, and the difficulty in separating various components of the waveform could explain that AoI evaluation does not have a clear clinical utility. Further research is underway to realise the full potential of this vessel in fetal cardiac and haemodynamically compromised pathological conditions. In this review article we outline the physiological origin of this Doppler waveform, describe in detail the various published indices, summarise the published literature to date, and finally outline potential future research and hopefully clinical applications. PMID- 27379711 TI - Investigation of the Roles of Allosteric Domain Arginine, Aspartate, and Glutamate Residues of Rhizobium etli Pyruvate Carboxylase in Relation to Its Activation by Acetyl CoA. AB - The mechanism of allosteric activation of pyruvate carboxylase by acetyl CoA is not fully understood. Here we have examined the roles of residues near the acetyl CoA binding site in the allosteric activation of Rhizobium etli pyruvate carboxylase using site-directed mutagenesis. Arg429 was found to be especially important for acetyl CoA binding as substitution with serine resulted in a 100 fold increase in the Ka of acetyl CoA activation and a large decrease in the cooperativity of this activation. Asp420 and Arg424, which do not make direct contact with bound acetyl CoA, were nonetheless found to affect acetyl CoA binding when mutated, probably through changed interactions with another acetyl CoA binding residue, Arg427. Thermodynamic activation parameters for the pyruvate carboxylation reaction were determined from modified Arrhenius plots and showed that acetyl CoA acts to decrease the activation free energy of the reaction by both increasing the activation entropy and decreasing the activation enthalpy. Most importantly, mutations of Asp420, Arg424, and Arg429 enhanced the activity of the enzyme in the absence of acetyl CoA. A main focus of this work was the detailed investigation of how this increase in activity occurred in the R424S mutant. This mutation decreased the activation enthalpy of the pyruvate carboxylation reaction by an amount consistent with removal of a single hydrogen bond. It is postulated that Arg424 forms a hydrogen bonding interaction with another residue that stabilizes the asymmetrical conformation of the R. etli pyruvate carboxylase tetramer, constraining its interconversion to the symmetrical conformer that is required for catalysis. PMID- 27379712 TI - Laparoscopic Repair of a Sciatic Hernia Containing the Ipsilateral Ovary: Case Report and Review of the Literature. AB - BACKGROUND: Sciatic hernia is a very rare pelvic floor hernia, but apparently its incidence has been growing in the past few years. The symptomatology is usually aspecific or absent, but in some cases complications such as intestinal obstruction, intractable pain, or urinary sepsis can occur. The usual treatment is the surgical correction of the defect, mainly with an open approach. CASE SUMMARY: We describe a case of sciatic hernia causing intermittent abdominal pain and subocclusive symptoms. The hernia has been treated with a laparoscopic technique using a polypropylene extraperitoneal mesh fixed with biological glue. The postoperative course of our patient was uneventful and at 3 months follow-up, no relapse or symptoms occurred. CONCLUSION: The laparoscopic treatment of this rare type of hernia appears to be a feasible and safe surgical option with all the advantages of the mini-invasive technique. PMID- 27379713 TI - Inhibitors of the Cysteine Synthase CysM with Antibacterial Potency against Dormant Mycobacterium tuberculosis. AB - Cysteine is an important amino acid in the redox defense of Mycobacterium tuberculosis, primarily as a building block of mycothiol. Genetic studies have implicated de novo cysteine biosynthesis in pathogen survival in infected macrophages, in particular for persistent M. tuberculosis. Here, we report on the identification and characterization of potent inhibitors of CysM, a critical enzyme in cysteine biosynthesis during dormancy. A screening campaign of 17 312 compounds identified ligands that bind to the active site with micromolar affinity. These were characterized in terms of their inhibitory potencies and structure-activity relationships through hit expansion guided by three dimensional structures of enzyme-inhibitor complexes. The top compound binds to CysM with 300 nM affinity and displays selectivity over the mycobacterial homologues CysK1 and CysK2. Notably, two inhibitors show significant potency in a nutrient-starvation model of dormancy of Mycobacterium tuberculosis, with little or no cytotoxicity toward mammalian cells. PMID- 27379714 TI - Incentive contrast effects regulate responding to a flavor presented in compound with a saccharin unconditioned stimulus in rats. AB - A flavor conditioned stimulus (conditional stimulus; CS) presented in simultaneous compound with a sweet-tasting unconditioned stimulus (US) acquires a certain sweetness and/or hedonic value. The present study examined whether responding to the flavor CS is influenced by postconditioning changes in the strength of the sweet US representation. In each experiment, rats were exposed to presentations of each of 2 flavors, A and B, in simultaneous compound with a 0.4% saccharin solution, and then tested with presentations of CS A in water. Experiments 1 and 2 showed that responding to CS A depended on its pairing with saccharin and increased with the training-to-test interval. Experiment 3 showed that a progressive reduction in the saccharin concentration of the trained compounds led to an increase in responding to CS A when tested in the absence of saccharin. Experiments 4 and 5 showed that, after a 7-day training-to-test delay, responding to CS A decreased following pretest exposure to a strong saccharin solution, and increased following pretest exposure to a very weak saccharin solution. These findings are taken to imply that incentive contrast effects regulate responding to a flavor CS. Hence, responding to the flavor CS increases with the training-to-test interval as the representation of the sweet US decays; decreases following pretest exposure to very sweet solutions as these reinstate the decayed sweet US representation (negative contrast); and increases following pretest exposure to weakly sweet solutions as these are perceived as less attractive than the CS itself (positive contrast). (PsycINFO Database Record PMID- 27379715 TI - Learning to inhibit the response during instrumental (operant) extinction. AB - Five experiments tested implications of the idea that instrumental (operant) extinction involves learning to inhibit the learned response. All experiments used a discriminated operant procedure in which rats were reinforced for lever pressing or chain pulling in the presence of a discriminative stimulus (S), but not in its absence. In Experiment 1, extinction of the response (R) in the presence of S weakened responding in S, but equivalent nonreinforced exposure to S (without the opportunity to make R) did not. Experiment 2 replicated that result and found that extinction of R had no effect on a different R that had also been reinforced in the stimulus. In Experiments 3 and 4, rats first learned to perform several different stimulus and response combinations (S1R1, S2R1, S3R2, and S4R2). Extinction of a response in one stimulus (i.e., S1R1) transferred and weakened the same response, but not a different response, when it was tested in another stimulus (i.e., S2R1 but not S3R2). In Experiment 5, extinction still transferred between S1 and S2 when the stimuli set the occasion for R's association with different types of food pellets. The results confirm the importance of response inhibition in instrumental extinction: Nonreinforcement of the response in S causes the most effective suppression of responding, and response suppression is specific to the response but transfers and influences performance of the same response when it is occasioned by other stimuli. Theoretical and practical implications are discussed. (PsycINFO Database Record PMID- 27379716 TI - A cumulative decision model for three-alternative choice in concurrent chains. AB - Traditional models for choice in the concurrent-chains procedure have assumed that terminal-link stimuli acquire value as conditioned reinforcers, and that 2 alternative choice provides a measure of relative value according to the matching law. By contrast, the cumulative decision model (CDM; Christensen & Grace, 2010) explains choice as the aggregate effect of comparing delays to a criterion on initial-link responding, not conditioned reinforcement. Here we test whether the CDM can account for choice in 3-alternative concurrent-chains (3ACC) and compare it with the hyperbolic value-added model (HVA; Mazur, 2001), which assumes that choice depends on the increase in conditioned reinforcement value signaled by terminal-link stimuli and has been successful in previous 3ACC research (Mazur, 2000). In Experiment 1, 4 pigeons responded in 3ACC in which the terminal links were fixed-interval schedules, and parameter estimates from fits of CDM and HVA were used to calculate predictions for conditions with variable-interval terminal links. The predictions of CDM were more accurate than those of HVA. In Experiment 2, 7 pigeons responded in 3ACC in which the terminal links were fixed-interval schedules. Although both models described the data well, residuals from HVA fits showed a systematic pattern predicted by CDM, characterized by a third-order polynomial with a negative cubic coefficient. Finally, we conducted a residual meta-analysis (Sutton, Grace, McLean, & Baum, 2008) of data from prior 3ACC studies. HVA residuals showed the same negative cubic pattern as in Experiment 2, whereas no systematic pattern was found in the CDM residuals. Overall, results support the CDM and suggest that the same principles which describe binary choice in concurrent chains generalize without modification to 3-alternative choice. (PsycINFO Database Record PMID- 27379717 TI - Cue salience influences the use of height cues in reorientation in pigeons (Columba livia). AB - Although orienting ability has been examined with numerous types of cues, most research has focused only on cues from the horizontal plane. The current study investigated pigeons' use of wall height, a vertical cue, in an open-field task and compared it with their use of horizontal cues. Pigeons were trained to locate food in 2 diagonal corners of a rectangular enclosure with 2 opposite high walls as height cues. Before each trial, pigeons were rotated to disorient them. In training, pigeons could use either the horizontal cues from the rectangular enclosure or the height information from the walls to locate the food. In testing, the apparatus was modified to provide (a) horizontal cues only, (b) height cues only, and (c) both height and horizontal cues in conflict. In Experiment 1 the lower and high walls, respectively, were 40 and 80 cm, whereas in Experiment 2 they were made more perceptually salient by shortening them to 20 and 40 cm. Pigeons accurately located the goal corners with horizontal cues alone in both experiments, but they searched accurately with height cues alone only in Experiment 2. When the height cues conflicted with horizontal cues, pigeons preferred the horizontal cues over the height cues in Experiment 1 but not in Experiment 2, suggesting that perceptual salience influences the relative weighting of cues. (PsycINFO Database Record PMID- 27379718 TI - Perceptual learning with tactile stimuli in rats: Changes in the processing of a dimension. AB - Four experiments with male rats investigated perceptual learning involving a tactile dimension (A, B, C, D, E), where A denotes 1 end of the continuum (e.g., a rough floor) and E the other (e.g., a smooth floor). In Experiment 1, rats given preexposure to A and E learned an appetitive discrimination between them more readily than those not given preexposure. Experiment 2a showed that rats preexposed to B and D acquired a discrimination between A and E more readily than those preexposed to A and E; and in Experiment 2b the same preexposure treatments had no effect on the acquisition of a discrimination between B and D. In Experiments 3a and 3b, rats given preexposure to C learned a discrimination between A and E more readily than those not given preexposure. Experiment 4 demonstrated that preexposure to a texture (e.g., B) that was adjacent to the to be-discriminated textures (e.g., C and E) facilitated a discrimination between them relative to preexposure to their midpoint (D). These novel perceptual learning effects are interpreted as reflecting a redistribution of processing between the notional elements of the texture dimension. (PsycINFO Database Record PMID- 27379719 TI - "Contexts control negative contrast and restrict the expression of flavor preference conditioning": Correction to Austen and Sanderson (2016). AB - Reports an error in "Contexts control negative contrast and restrict the expression of flavor preference conditioning" by Joseph M. Austen and David J. Sanderson (Journal of Experimental Psychology: Animal Learning and Cognition, 2016[Jan], Vol 42[1], 95-105). In Table 2 of the article, the conditions in Experiment 3 are labeled AB and XY, but they should be AX and BY. (The following abstract of the original article appeared in record 2015-59080-002.) Consumption of a high concentration of sucrose can have either a detrimental, negative contrast effect or a facilitatory, preference conditioning effect on subsequent consumption of a low concentration of sucrose, depending on the cues that are present during consumption. The role of context and flavor cues in determining these effects were studied using analysis of the microstructure of licking in mice. Exposure to a high concentration followed by exposure to a low concentration resulted in a transient reduction in mean lick cluster size, which was context dependent (Experiment 1). However, there was no change in the total number of licks or overall consumption. When a flavor that had previously been paired with a high concentration was paired with a low concentration, there was an increase in the total number of licks, and overall consumption, but no change in the mean lick cluster size (Experiment 2). Pairing a high concentration with a flavor in a particular context before pairing the context and flavor compound with a low concentration resulted in abolishing the expression of the flavor preference conditioning effect on the total number of licks and consumption (Experiment 3). These results demonstrate that although context and flavor cues have dissociable effects on licking behavior, their interaction has an antagonistic effect on the behavioral expression of memory. (PsycINFO Database Record PMID- 27379720 TI - Switching off perceptual learning: Anodal transcranial direct current stimulation (tDCS) at Fp3 eliminates perceptual learning in humans. AB - Perceptual learning can be acquired as a result of experience with stimuli that would otherwise be difficult to tell apart, and is often explained in terms of the modulation of feature salience by an error signal based on how well that feature can be predicted by the others that make up the stimulus. In this article we show that anodal transcranial Direct Current Stimulation (tDCS) at Fp3 directly influences this modulation process so as to eliminate and possibly reverse perceptual learning. In 2 experiments, anodal stimulation disrupted perceptual learning (indexed by an inversion effect) compared with sham (Experiment 1) or cathodal (Experiment 2) stimulation. Our findings can be interpreted as showing that anodal tDCS severely reduced or even abolished the modulation of salience based on error, greatly increasing generalization between stimuli. This result supports accounts of perceptual learning based on variations in salience as a consequence of pre-exposure, and opens up the possibility of controlling this phenomenon. (PsycINFO Database Record PMID- 27379723 TI - Dental Implant Length and Diameter: A Proposed Classification Scheme. AB - PURPOSE: To propose a length-and-diameter-based classification scheme for dental implants to standardize terminology in the dental literature and communication between interested parties. MATERIALS AND METHODS: This study was mainly based on searching two major resources: published scientific research papers and 14 of the most popular dental implant manufacturers. Indexed databases were searched from January 2004 up to and including February 2016 using the keywords "dental implant length" and "dental implant diameter." Retrieved titles and abstracts were screened, and related full-text articles were reviewed. Full-text articles that clearly stated the terms and measurements of implants used were included and considered for proposing this classification scheme. RESULTS: The initial search for implant diameter and length yielded 1007 and 936 articles, respectively. A total of 85 studies (41 about diameter, 44 about length) were selected and reviewed. The remaining studies (966 about diameter, 892 about length) that did not abide by the eligibility criteria were excluded. The terms "long," "short," "standard," "wide," and "narrow" were the most commonly used terms in the literature. A classification scheme for implants by diameter and length was proposed. CONCLUSIONS: Indexed publications contain a variety of terms used by authors to describe diameter and length of dental implants without conformity and standardization. The classification scheme proposed in this article could serve as a reference for interested parties. PMID- 27379722 TI - Nuclear import sequence identification in hOAS3 protein. AB - OBJECTIVE: The OAS proteins are characterized by their capacity to synthesize 2',5'-linked phosphodiester bonds to polymerize ATP into oligomers of adenosine. OAS3, belonging to OASs gene family, synthesizes dimeric 2-5A that binds to RNase L with low affinity and produces 2-5A oligomers shorter than the tri-tetramer 2 5As produced by other family members. METHODS: For these studies, we used the open source tools cNLS Mapper, PredictProtein and COMPARTMENTS for the nuclear localization signal prediction, UCSF Chimera for molecular graphics and analyses, The Human Protein Atlas to confirm with the IF the OAS3 cell localization and Ensembl Variation Table to identify the presence of putative single nucleotide polymorphisms in the NLS sequence identification. RESULTS: The analysis of OAS3 protein sequence (NP_006178.2) displayed a putative nuclear localization signal (cNLS Mapper score 8 and PP 100 %), identified by 11 and 5 amino acids (LQRQL KRPRP V) located in the outer portion ready to interact with the importin alpha/beta. Furthermore, we showed that in all cells lines available in the Human Protein Atlas subcell section, the OAS3 was mainly localized in the cytoplasm and nucleus, but not in the nucleoli. We identify six known variant SNPs mapping in the nuclear import sequence, but only three were associated with a missense variation (rs781335794, rs750458641, rs550465943) and were able to strongly reduce the cNLS score. CONCLUSIONS: The catalytically inactive domain of human OAS3 has a potential nuclear import function, susceptible to SNPs, which could determine their roles in the viral infection and IFNs response. PMID- 27379724 TI - American neurophysiology and two nineteenth-century American Physiological Societies. AB - This article contrasts two American Physiological Societies, one founded near the beginning of the nineteenth century in 1837 and the other founded near its end in 1887. The contrast allows a perspective on how much budding neuroscience had developed during the nineteenth century in America. The contrast also emphasizes the complicated structure needed in both medicine and physiology to allow neurophysiology to flourish. The objectives of the American Physiological Society of 1887 were (and are) to promote physiological research and to codify physiology as a discipline. These would be accomplished by making physiology much more inclusive than traditionally accepted by raising research standards, by giving prestige to its members, by providing members a source of professional interchange, by protecting its members from antivivisectionists, and by promoting physiology as fundamental to medicine. The quantity of neuroscientific experiments by its members was striking. The main organizers of the society were Silas Weir Mitchell, John Call Dalton, Henry Pickering Bowditch, and Henry Newell Martin. The objective of the American Physiological Society of 1837 was to disperse knowledge of the "laws of life" and to promote human health and longevity. The primary organizers were William Andrus Alcott and Sylvester Graham with the encouragement of John Benson. Its technique was to use physiological information, not create it as was the case in 1887. Its object was to disseminate the word that healthy eating will improve the quality of life. PMID- 27379721 TI - The cannabinoid 2 receptor agonist beta-caryophyllene modulates the inflammatory reaction induced by Mycobacterium bovis BCG by inhibiting neutrophil migration. AB - OBJECTIVE AND DESIGN: beta-Caryophyllene (BCP) is a sesquiterpene that binds to the cannabinoid 2 (CB2) receptor and exerts anti-inflammatory effects. In this study, we investigated the anti-inflammatory effect of BCP and another CB2 agonist, GP1a in inflammatory experimental model induced by Mycobacterium bovis (BCG). METHODS: C57Bl/6 mice were pretreated orally with BCP (0.5-50 mg/kg) or intraperitonealy with GP1a (10 mg/kg) 1 h before the induction of pleurisy or pulmonary inflammation by BCG. The direct action of CB2 agonists on neutrophils function was evaluated in vitro. RESULTS: beta-Caryophyllene (50 mg/kg) impaired BCG-induced neutrophil accumulation in pleurisy without affecting mononuclear cells or the production of TNF-alpha and CCL2/MCP-1. However, BCP inhibited CXCL1/KC, leukotriene B4 (LTB4), IL-12, and nitric oxide production. GP1a had a similar effect to BCP. Preincubation of neutrophils with BCP (10 uM) impaired chemotaxis toward LTB4 and adhesion to endothelial cells stimulated with TNF alpha, and both, BCP and GP1a, impaired LTB4-induced actin polymerization. CONCLUSION: These results suggest that the CB2 receptor may represent a new target for modulating the inflammatory reaction induced by mycobacteria. PMID- 27379725 TI - Radiological predictors of malignant transformation of IPMNs: importance of the predictive model validation: Author reply. PMID- 27379726 TI - Arc discharge-mediated disassembly of viral particles in water. AB - In this study, we investigated the inactivation effects on murine norovirus (MNV 1) with/without purification in water using a submerged plasma reactor of arc discharge (underwater arc), which produced a shockwave, UV light, reactive oxygen species and reactive nitrogen species. Underwater arc treatments of 3 and 6 Hz at 12 kV resulted in 2.6- and 4.2-log reductions in the virus titer of non-purified MNV-1 after 1 min of treatment, respectively. The reduction of purified MNV-1 was higher than that of non-purified MNV-1 after underwater arc treatment for all applied conditions (12 or 15 kV and 3 or 6 Hz). One of the viral capsid proteins (VP1) was not detectable after underwater arc treatment, when its integrity was assessed by western blot analysis. Transmission electron microscopy analysis also revealed that MNV-1 particles were completely dissembled by the treatment. This study demonstrates that underwater arc treatment, which was capable of disintegrating the MNV-1 virion structure and the viral capsid protein, can be an effective disinfection process for the inactivation of water-borne noroviruses. PMID- 27379727 TI - Effect of co-existing kaolinite and goethite on the aggregation of graphene oxide in the aquatic environment. AB - Broad applications of graphene oxide (GO) will result in the release of GO into aquatic environments, where clay minerals and metal (hydr)oxides are commonly present. Thereby the interactions between GO and a binary system containing clay minerals and metal (hydr)oxides can occur. We investigated the aggregation of GO with kaolinite and kaolinite-goethite associations (KGAs) in aquatic systems under different pHs, ionic strengths, and GO concentrations. GO suspension was unstable at low pHs, and the aggregation of GO occurred in the presence of KGA-4% and KGA-10% until pH 5 and 6, respectively. Kaolinite decreased the critical coagulation concentration (CCC) of GO at pH 5.5 from around 50 to 20 mM NaCl due to the reduced energy barrier. Heteroaggregation of GO with KGAs was extremely sensitive to ionic strength at pH 5.5, and the CCC of GO in the presence of KGA 10% increased from less than 1 mM NaCl to 5 mM NaCl with the increase of pH from 5.5 to 9. The heteroaggregation extent of GO with KGAs was enhanced firstly, then reduced with the increase of GO concentrations at pH 5.0, which is likely because KGA plates were more efficiently wrapped by large-size GO sheets with increasing GO concentrations. These findings are useful for understanding and predicting the fate of GO in the relatively complicated aquatic and soil environments where binary minerals co-exist. PMID- 27379729 TI - Life cycle water footprint of hydrogenation-derived renewable diesel production from lignocellulosic biomass. AB - The conversion of lignocellulosic biomass to biofuel requires water. This study is focused on the production of hydrogenation-derived renewable diesel (HDRD) from lignocellulosic biomass. Although there has been considerable focus on the assessment of greenhouse gas (GHG) emissions, there is limited work on the assessment of the life cycle water footprint of HDRD production. This paper presents a life cycle water consumption study on lignocellulosic biomass to HDRD via pyrolysis and hydrothermal liquefaction (HTL) processes. The results of this study show that whole tree (i.e., tree chips) biomass has water requirements of 497.79 L/MJ HDRD and 376.16 L/MJ HDRD for production through fast pyrolysis and the HTL process, respectively. Forest residues (i.e., chips from branches and tops generated during logging operations) have water requirements of 338.58 L/MJ HDRD and 255.85 L/MJ HDRD for production through fast pyrolysis and the HTL process, respectively. Agricultural residues (i.e., straw from wheat, oats, and barley), which are more water efficient, have water requirements of 83.7 L/MJ HDRD and 59.1 L/MJ HDRD through fast pyrolysis and the HTL process, respectively. Differences in water use between feedstocks and conversion processes indicate that the choices of biomass feedstock and conversion pathway water efficiency are crucial factors affecting water use efficiency of HDRD production. PMID- 27379728 TI - Pathways regulating the removal of nitrogen in planted and unplanted subsurface flow constructed wetlands. AB - Single-stage constructed wetlands (CWs) are characterized by a low potential for N removal. Understanding the pathways regulating N cycling as well as their dependence on environmental variables might improve the potential of CWs for N removal and results in more accurate simulation tools. In this study we employed qPCR targeting marker functional genes (amoA, nirK, nirS, clade I and II nosZ) or microorganisms (anammox) regulating key pathways of N cycling to unravel their relative importance. Furthermore, the influence of plant species on treatment performance was studied. Our findings indicated nitrification-denitrification as the principal route of N removal in CWs, while anammox did not have a strong contribution. Evidence was also arisen that ammonia oxidizing archaea (AOA) contributed on NH3 oxidation. Overall, plant species had a weak effect on the abundance of N functional genes (amoA of AOA), but it strongly affected the performance of CWs in terms of N removal in the following order: unplanted < Phragmites communis < Typha latifolia. These findings suggest that plant species stimulate N removal by upregulating the rates that the responsible biochemical pathways operate, probably by increasing O2 supply. In addition, our study revealed differences in indicators linked to N2O emissions. The abundance of clade II nosZ genes remained low across the season scaling down a strong contribution in the reduction of the emitted N2O. The increasing ratios of nosZ/Sigmanir and nirS/nirK with the progress of season indicate a shift in the composition of denitrifiers towards strains with a lower genetic potential for N2O release. Similar trends were observed among the treatments but the mechanisms differed. The planted treatments stimulated an increase in the SigmanosZ/Sigmanir ratio, while the unplanted an increase in the nirS/nirK ratio. PMID- 27379730 TI - Retinal Pigment Epithelium Tear after Immunosuppressive Treatment for Sarcoidosis related Choroidal Granuloma. AB - PURPOSE: To describe the formation of a retinal pigment epithelial (RPE) tear following immunosuppressive treatment of a large choroidal granuloma in a patient with sarcoidosis-related panuveitis. METHODS: A 25-year-old woman presented with bilateral sarcoidosis-related panuveitis and optic disc edema in both eyes with a large choroidal granuloma temporal to the fovea in the left eye. High-dose oral prednisone therapy was given. RESULTS: High-dose oral prednisone therapy produced improvement in her panuveitis with reduction in size of the left choroidal granuloma. An RPE tear overlying the flattening choroidal granuloma developed by 3 weeks of treatment. CONCLUSIONS: Treatment of choroidal granuloma with rapid reduction in size may result in an RPE tear. PMID- 27379731 TI - Risk of Bleeding and Thrombosis in Patients 70 Years or Older Using Vitamin K Antagonists. AB - IMPORTANCE: Previous studies have shown that, despite the higher risk of bleeding, the elderly still benefit from taking anticoagulants if they have a stringent indication. However, owing to the relatively low number of patients older than 90 years in these studies, it is unknown whether this benefit is also seen with the eldest patients. OBJECTIVE: To determine how the risk of bleeding and thrombosis is associated with age in patients older than 70 years who were treated with a vitamin K antagonist (VKA). DESIGN, SETTING, AND PARTICIPANTS: A matched cohort study was conducted of patients at a thrombosis service who were treated with a VKA between January 21, 2009, and June 30, 2012. All 1109 patients 90 years or older who were treated with a VKA were randomly matched 1:1:1 with 1100 patients aged 80 to 89 years and 1104 patients aged 70 to 79 years based on duration of VKA treatment. Data analysis was conducted from April 2015 to April 2016. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of clinically relevant nonmajor and major bleeding. Secondary outcomes included thromboses and quality of VKA control. RESULTS: During 6419 observation-years, 713 of the 3313 patients (1394 men and 1919 women) had 1050 bleeding events. The risk of bleeding was not significantly increased in patients aged 80 to 89 years (event rate per 100 patient-years [ER], 16.7; hazard ratio [HR], 1.07; 95% CI, 0.89-1.27) and mildly increased in patients 90 years or older (ER, 18.1; HR, 1.26; 95% CI, 1.05-1.50) compared with patients aged 70 to 79 years (ER, 14.8). The point estimates for major bleeding (including fatal) were comparable for patients aged 80 to 89 years (ER, 1.0; HR, 1.09; 95% CI, 0.60-1.98) and those 90 years or older (ER, 1.1; HR, 1.20; 95% CI, 0.65-2.22) compared with those aged 70 to 79 years (ER, 0.9). The increase in bleeding risk was sharper in men than in women. Eighty-five patients (2.6%) developed a thrombotic event. Risk of thrombosis was higher for patients in their 90s (HR, 2.14; 95% CI, 1.22-3.75) and 80s (HR, 1.75; 95% CI, 1.002-3.05) than for patients in their 70s. Vitamin K antagonist control became significantly poorer with rising age, which partly explained the increased bleeding risk in patients 90 years or older, but most of the increased risk of thrombosis was not mediated by VKA control. CONCLUSIONS AND RELEVANCE: These clinical practice data of patients considered eligible for anticoagulation show that the bleeding risk with a VKA only mildly increases after the age of 80 years, while there is a sharp increase in the risk of thrombosis in the same age group. PMID- 27379734 TI - Photophysics of Diphenylbutadiynes in Water, Acetonitrile-Water, and Acetonitrile Solvent Systems: Application to Single Component White Light Emission. AB - Diacetylenes have been the subject of current research because of their interesting optoelectronic properties. Herein, we report that substituted diphenylbutadiynes exhibit locally excited (LE) and excimer emissions in water and multiple emissions from the LE, excimer, and intramolecular charge transfer (ICT) states in acetonitrile-water solvent systems. The LE, excimer, and ICT emissions are clearly distinguishable for a diphenylbutadiynyl derivative with push (-NMe2)-pull (-CN) substituents and those are closely overlapped for non push-pull analogues. In neat acetonitrile, the excimer emission disappears and the LE and ICT emissions predominate. In the case of the push (-NMe2)-pull (-CN) diphenylbutadiyne, the intensity of the ICT emission increases with increasing the fluorophore concentration. This suggests that the ICT emission accompanies with intermolecular CT emission which is of exciplex type. As the LE and exciplex emissions of the push-pull diphenylbutadiyne together cover the visible region (400-700 nm) in acetonitrile, a control of the fluorophore concentration makes the relative intensities of the LE and exciplex emissions such that pure white light emission is achieved. The white light emission is not observed in those diphenylbutadiynyl analogues in which the peripheral substituents of the phenyl rings do not possess strong push-pull character. PMID- 27379732 TI - Association of functional status and treatment choice among older men with prostate cancer in the Medicare Advantage population. AB - BACKGROUND: There are several effective treatments for prostate cancer. To what extent a patient's functional status influences the treatment decision is unknown. This study examined the association between functional status and treatment among older men with prostate cancer. METHODS: Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey data were used to identify men who were 65 years old or older and were diagnosed with prostate cancer between 1998 and 2009. The primary outcome was treatment choice: conservative management, surgery, or radiation within 1 year of the diagnosis. The exposure was the functional status assessed as 4 measures within 3 domains: 1) physical function (activities of daily living [ADLs] and physical component summary score), 2) cognitive function (survey completer: self vs proxy), and 3) emotional well-being (mental component summary score). A multivariate, multinomial logistic regression was fitted with adjustments for several patient, tumor, and regional characteristics. RESULTS: This study identified 508 conservative management patients, 195 surgery patients, and 603 radiation patients. Compared with men with no ADL dependency, those with any ADL dependency had lower odds of receiving surgery (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.38-0.99) or radiation (OR, 0.58; 95% CI, 0.43-0.78) versus conservative management. ADL dependency did not differ when surgery and radiation were compared. Patients with a proxy survey response were less likely to receive surgery or radiation versus conservative management. CONCLUSIONS: Functional status is associated with treatment choice for men with prostate cancer. Future research should examine whether this is due to physician recommendations, patient preferences, or a combination. Cancer 2016;122:3199-206. (c) 2016 American Cancer Society. PMID- 27379733 TI - Dipeptidyl peptidase-4 inhibitors and bone metabolism: is vitamin D the link? AB - AIMS: Dipeptidyl peptidase-4 inhibitors (DPP4-Is) represent a promising class of agents for type 2 diabetes treatment. Experimental models and clinical studies have reported positive effects of DPP4-Is on bone; however, how DPP4-Is positively impact bone homeostasis in humans remains an unanswered question. Aim of this study investigated the relationship between treatment with DPP4-Is and vitamin D balance in patients with type 2 diabetes. METHODS: This is a cross sectional study. A total of 295 consecutive individuals with type 2 diabetes referring to our diabetes outpatient clinics were enrolled; among them, 53 % were in treatment with DPP4-Is. Metabolic profile and routine biochemistry were assessed by standard methods; serum 25(OH) vitamin D levels [25(OH)D] were measured by colorimetric method (LAISON, DiaSorin). RESULTS: DPP4-Is-treated participants had significantly higher serum 25(OH)D levels then those undertaking other antidiabetic therapies (18.4 +/- 10.7 vs. 14.9 +/- 8.6 ng/ml, p = 0.004); this association persisted after adjusting for all major confounders. Increased 25(OH)D concentrations also correlated with the duration of DPP4-Is treatment and with a stronger DPP4 inhibitory activity. CONCLUSIONS: DPP4-Is treatment is associated with improved vitamin D balance in people with type 2 diabetes; our findings suggest that vitamin D may underlie the link between DPP4-Is and bone metabolism. PMID- 27379736 TI - [Therapy-resistant cells of the B cell line]. PMID- 27379735 TI - Low-Level Laser Irradiation Improves Depression-Like Behaviors in Mice. AB - Major depressive disorder (MDD) is one of the leading forms of psychiatric disorders, characterized by aversion to mobility, neurotransmitter deficiency, and energy metabolic decline. Low-level laser therapy (LLLT) has been investigated in a variety of neurodegenerative disorders associated with mitochondrial dysfunction and functional impairments. The goal of this study was to examine the effect of LLLT on depression-like behaviors and to explore the potential mechanism by detecting mitochondrial function following LLLT. Depression models in space restriction mice and Abelson helper integration site-1 (Ahi1) knockout (KO) mice were employed in this work. Our results revealed that LLLT effectively improved depression-like behaviors, in the two depression mice models, by decreasing immobility duration in behavioral despair tests. In addition, ATP biosynthesis and the level of mitochondrial complex IV expression and activity were significantly elevated in prefrontal cortex (PFC) following LLLT. Intriguingly, LLLT has no effects on ATP content and mitochondrial complex I-IV levels in other tested brain regions, hippocampus and hypothalamus. As a whole, these findings shed light on a novel strategy of transcranial LLLT on depression improvement by ameliorating neurotransmitter abnormalities and promoting mitochondrial function in PFC. The present work provides concrete groundwork for further investigation of LLLT for depression treatment. PMID- 27379737 TI - [Standardized outcome parameters]. PMID- 27379738 TI - [Clinical immunology in rheumatology : State of the art]. PMID- 27379739 TI - [Pachydermodactyly : A rare but benign consequence of repetitive movement patterns]. AB - Pachydermodactyly is an acquired swelling of the lateral aspects of the fingers and is thought to be a reactive pattern due to exogenous factors, such as repetitive mechanical friction. We describe the clinical case of a 17-year-old male patient who presented with the typical symptoms of pachydermodactyly. PMID- 27379740 TI - [Medical treatment of rheumatoid arthritis in 2014 : Current data from the German Collaborative Arthritis Centers]. AB - BACKGROUND: Since the introduction of biologic treatment in rheumatoid arthritis (RA), disease activity and treatment modalities have changed substantially. The current provision and developments in recent years are analyzed with annual data from the National Database of the Collaborative Arthritis Centers in Germany. METHODS: To analyze disease activity, diagnostics and treatment in RA patients in 2014 with regard to seropositivity and disease duration. Time trends from 2007 2014 are reported for disease activity (DAS28) distribution and biologic treatment. RESULTS: In 2014, a total of 8,084 RA patients were analyzed: 72 % were rheumatoid factor and/or ACPA positive, the mean age was 62 years and the mean disease duration 12 years. According to DAS28, 35.9 % were in remission, 19.2 % had low, 37.1 % moderate and 7.8 % high disease activity. An increase since 2007 was only observed in patients with a disease duration >2 years. Synthetic DMARDS were used for treatment in 78 %. Biologic treatment increased from 16 % (2007) to 27 % (2014). Especially those patients with a disease duration >5 years were treated more frequently with biologics. Seronegative patients had slightly less severe mean disease activity parameters. They were treated equally frequent with DMARDS but only half as often with biologics compared to seropositive patients. CONCLUSION: The use of biologics in RA patients has increased since 2007; however this was not observed in patients with short disease duration. Early intensive treatment adaption seems justified to improve disease activity in the large portion of patients who do not reach low disease activity under conventional DMARDs. PMID- 27379741 TI - [Synovial fibroblasts : Main players in rheumatoid arthritis]. PMID- 27379742 TI - Use of Decision Models in the Development of Evidence-Based Clinical Preventive Services Recommendations: Methods of the U.S. Preventive Services Task Force. AB - The U.S. Preventive Services Task Force (USPSTF) develops evidence-based recommendations about preventive care based on comprehensive systematic reviews of the best available evidence. Decision models provide a complementary, quantitative approach to support the USPSTF as it deliberates about the evidence and develops recommendations for clinical and policy use. This article describes the rationale for using modeling, an approach to selecting topics for modeling, and how modeling may inform recommendations about clinical preventive services. Decision modeling is useful when clinical questions remain about how to target an empirically established clinical preventive service at the individual or program level or when complex determinations of magnitude of net benefit, overall or among important subpopulations, are required. Before deciding whether to use decision modeling, the USPSTF assesses whether the benefits and harms of the preventive service have been established empirically, assesses whether there are key issues about applicability or implementation that modeling could address, and then defines the decision problem and key questions to address through modeling. Decision analyses conducted for the USPSTF are expected to follow best practices for modeling. For chosen topics, the USPSTF assesses the strengths and limitations of the systematically reviewed evidence and the modeling analyses and integrates the results of each to make preventive service recommendations. PMID- 27379744 TI - High-Throughput Screening Across Quaternary Alloy Composition Space: Oxidation of (AlxFeyNi1-x-y)~0.8Cr~0.2. AB - Composition spread alloy films (CSAFs) are commonly used as libraries for high throughput screening of composition-property relationships in multicomponent materials science. Because lateral gradients afford two degrees of freedom, an n component CSAF can, in principle, contain any composition range falling on a continuous two-dimensional surface through an (n - 1)-dimensional composition space. However, depending on the complexity of the CSAF gradients, characterizing and graphically representing this composition range may not be straightforward when n >= 4. The standard approach for combinatorial studies performed using quaternary or higher-order CSAFs has been to use fixed stoichiometric ratios of one or more components to force the composition range to fall on some well defined plane in the composition space. In this work, we explore the synthesis of quaternary Al-Fe-Ni-Cr CSAFs with a rotatable shadow mask CSAF deposition tool, in which none of the component ratios are fixed. On the basis of the unique gradient geometry produced by the tool, we show that the continuous quaternary composition range of the CSAF can be rigorously represented using a set of two dimensional "pseudoternary" composition diagrams. We then perform a case study of (AlxFeyNi1-x-y)~0.8Cr~0.2 oxidation in dry air at 427 degrees C to demonstrate how such CSAFs can be used to screen an alloy property across a continuous two dimensional subspace of a quaternary composition space. We identify a continuous boundary through the (AlxFeyNi1-x-y)~0.8Cr~0.2 subspace at which the oxygen uptake into the CSAF between 1 and 16 h oxidation time increases abruptly with decreasing Al content. The results are compared to a previous study of the oxidation of AlxFeyNi1-x-y CSAFs in dry air at 427 degrees C. PMID- 27379743 TI - Investigating the KNDy Hypothesis in Humans by Coadministration of Kisspeptin, Neurokinin B, and Naltrexone in Men. AB - CONTEXT: A subpopulation of hypothalamic neurons colocalize three neuropeptides, namely kisspeptin, neurokinin B (NKB), and dynorphin, collectively termed KNDy neurons. Animal studies suggest they interact to affect pulsatile GnRH release (KNDy hypothesis); kisspeptin stimulates, NKB modulates, and dynorphin (an opioid) inhibits. OBJECTIVE: To investigate the KNDy hypothesis in humans, we assessed for the first time the effects of the coadministration of kisspeptin-54, NKB, and an opioid receptor antagonist, naltrexone, on LH pulsatility (surrogate marker for GnRH pulsatility) and gonadotropin release. DESIGN, SETTING, AND PARTICIPANTS: This was an ethically approved prospective, single-blinded, placebo controlled study. Healthy male volunteers (n = 5/group) attended our research facility for eight study visits. INTERVENTION AND MAIN OUTCOME MEASURE: After 1 hour of baseline blood sampling, participants received a different intervention at each visit: oral 50 mg naltrexone, 8-hour iv infusions of vehicle, 2.56 nmol/kg . h NKB, 0.1 nmol/kg . h kissspeptin-54 (KP) alone and in combination. Frequent blood sampling to measure plasma gonadotropins and sex steroids was conducted and LH pulsatility was determined using blinded deconvolution analysis. RESULTS: All kisspeptin and naltrexone containing groups potently increased LH and LH pulsatility (P < .001 vs vehicle). NKB alone did not affect gonadotropins. NKB+KP had significantly lower increases in gonadotropins compared with kisspeptin alone (P < .01). Naltrexone+KP was the only group to significantly increase LH pulse amplitude (P < .001 vs vehicle). CONCLUSIONS: Our results suggest significant interactions between the KNDy neuropeptides on LH pulsatility and gonadotropin release in humans. This has important implications for improving our understanding of GnRH pulse generation in humans. PMID- 27379745 TI - A randomized controlled trial of attention bias modification training for socially anxious adolescents. AB - The current study aimed to examine the efficacy of attention bias modification (ABM) training to reduce social anxiety in a community-based sample of adolescents 15-18 years. The study used a single-blind, parallel group, randomized controlled trial design (Clinical Trials ID: NCT02270671). Participants were screened in second-level schools using a social anxiety questionnaire. 130 participants scoring >=24 on the Social Phobia and Anxiety Inventory for Children (SPAI-C) were randomized to the ABM training (n = 66)/placebo (n = 64) group, 120 of which completed pre-, post-, and 12-week follow-up data collection including threat bias, anxiety, and depression measures. The ABM intervention included 4 weekly training sessions using a dot probe task designed to reduce attention bias to threatening stimuli. ABM training did not alter the primary outcomes of attention bias to threat or social anxiety symptoms raising questions about the efficacy of ABM as an intervention for adolescents. PMID- 27379746 TI - Semi-synthesis and NMR spectral assignments of flavonoid and chalcone derivatives. AB - Previous investigations of the aerial parts of the Australian plant Eremophila microtheca and Syzygium tierneyanum resulted in the isolation of the antimicrobial flavonoid jaceosidin (4) and 2',6'-dihydroxy-4'-methoxy-3',5' dimethyl chalcone (7), respectively. In this current study, compounds 4 and 7 were derivatized by acetylation, pivaloylation, and methylation reactions. The final products, 5,7,4'-triacetoxy jaceosidin (10), 5,7,4'-tripivaloyloxy jaceosidin (11), 5,7,4'-trimethoxy jaceosidin (12), 2',6'-diacetoxy-4'-methoxy 3',5'-dimethyl chalcone (13), 2'-hydroxy-4'-methoxy-6'-pivaloyloxy-3',5'-dimethyl chalcone (14), and 2'-hydroxy-4',6'-dimethoxy-3',5'-dimethyl chalcone (15) were all fully characterized by NMR and MS. Derivatives 10 and 13 have been previously reported but were only partially characterized. This is the first reported synthesis of 11 and 14. The natural products and their derivatives were evaluated for their antibacterial and antifungal properties, and the natural product, jaceosidin (4) and the acetylated derivative, 5,7,4'-triacetoxy jaceosidin (10), showed modest antibacterial activity (32-128 ug/ml) against Staphylococcus aureus strains. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27379747 TI - A highly sensitive LC-MS/MS method for determination of ketoconazole in human plasma: Application to a clinical study of the exposure to ketoconazole in patients after topical administration. AB - A simple, rapid and highly sensitive LC-MS/MS method was developed and validated for the determination of ketoconazole in human plasma. Sample preparation was accomplished through a single step liquid-liquid extraction by ethyl acetate. The chromatography separation was carried out on a Hedera CN (150mm*2.1mm, 5MUm) column with isocratic elution using acetonitrile and 10mM ammonium acetate containing 0.1% formic acid (45:55, v/v) as the mobile phase. The flow rate was 0.5mL/min. Detection was performed in the positive ion electrospray ionization mode using multiple reaction monitoring of the transitions of 531.2->489.3 and 286.1->217.1 for ketoconazole and letrozole (the internal standard), respectively. The method exhibited good linearity over the concentration range of 0.01-12ng/mL for ketoconazole. The intra- and inter-batch precision and accuracy of ketoconazole were all within the acceptable criteria. The method was successfully applied to a clinical study of the exposure to ketoconazole in Chinese seborrheic dermatitis patients after topical administration of two ketoconazole formulations of foam and lotion, respectively. The study results showed that there was little systemic absorption of ketoconazole in patients for the two formulations, and the ketoconazole foam and lotion are safe therapeutic drugs for seborrheic dermatitis patients. PMID- 27379748 TI - Internal hernia through a congenital peritoneal defect in the vesico-uterine space. AB - INTRODUCTION: An internal hernia is a rare type of hernia that may either be congenital or acquired in etiology. Acquired internal hernias generally develop from mesenteric defects or adhesions from prior surgery. These hernias can trap and/or twist small bowel, resulting in bowel obstruction. The diagnosis of small bowel obstruction (SBO) secondary to internal hernia is particularly challenging given its non-specific clinical presentation. Thus, it is critical for the clinician to keep internal hernias as part of the differential for a patient presenting with SBO. PRESENTATION OF CASE: In this case, we present the first reported case of a hernia through the vesico-uterine space as a cause of an SBO. Our patient was a 38-year-old female with no past medical or surgical history who presents with nausea, vomiting, and obstipation. Upon exploratory laparoscopy, she was found to have an internal hernia through a peritoneal defect in the vesico-uterine space. DISCUSSION: To our knowledge this is the first report of an intestinal obstruction caused by herniated bowel through a congenital vesico uterine peritoneal defect. It is important for surgeons to keep in mind that while rare, congenital pelvic peritoneal defects can lead to bowel obstructions. CONCLUSION: The patient underwent laparoscopic exploration, during which the incarcerated bowel was freed and appeared to be viable. The peritoneal defect was subsequently closed. Post-operatively, she recovered without issues and her obstructive symptoms resolved. PMID- 27379749 TI - Individualized multimodal treatment strategy for anaplastic thyroid carcinoma Case report of long-term remission and review of literature. AB - INTRODUCTION: The prognosis of anaplastic thyroid cancer (ATC) is poor with a mean survival time of six months following diagnosis. Despite various attempts to modify common treatment modalities including surgery, external beam radiation and chemotherapy, an effective treatment is not available yet. We report, here, a patient who achieved long-term survival based on multimodal treatment, including in vitro evaluation of drug response of his tumor cells. PRESENTATION OF CASE: A 42 years old male patient underwent total thyroidectomy with central and lateral neck dissection for ATC (pT4b, pN0 (0/36), L0, V0, Pn1, R0 cM0 - UICC-Stage: IV b). From the tumor tissue a primary cell culture was established. While the patient received a combined radio-chemotherapy cell viability assays were performed using Sorafenib, Vandetanib und MLN8054 (Aurora kinase inhibitor) as inhibitors. Cell viability was determined by MTT-assay after 72 and 144h of treatment. DISCUSSION: All the three compounds affected cell viability in a time- and dose dependent manner. These effects were most pronounced by Sorafenib. Based on in vitro findings, the patient was treated daily with 400mg Sorafenib for 75days. 43 months after initial diagnosis, the patient had no evidence of disease as shown by MRI, CT and FDG-PET-CT imaging. CONCLUSION: In the setting of multimodal treatment, in vitro drug evaluation of individual tumor cells of patients might be a promising tool to ameliorate the fatal prognosis of selected ATC patients. PMID- 27379750 TI - Laparoscopic transhiatal esophagectomy for esophageal adenocarcinoma identified at laparoscopic Roux-en-Y gastric bypass. AB - INTRODUCTION: More than one third of Americans are obese. Obesity is a risk factor for gastroesophageal reflux disease (GERD) and esophageal adenocarcinoma (EA). The only durable treatment for morbid obesity and its comorbid conditions is bariatric surgery. There is no consensus among bariatric surgeons, however, regarding the role of preoperative screening upper endoscopy in bariatric surgery. PRESENTATION OF CASE: Two cases of incidental EA were identified by completion EGD following laparoscopic Roux-en-Y gastric bypass (LRYGB). EGD was done for anastomotic surveillance and provocative leak testing. Esophageal masses were identified and biopsies demonstrated adenocarcinoma. In both cases a laparoscopic transhiatal esophagectomy (LTHE) was completed using the gastric remnant as conduit; the biliopancreatic limb was divided proximal to the jejunojejunostomy and anastomosed to the proximal roux limb to complete the reconstruction. DISCUSSION: Obesity is a risk factor for GERD and EA. The role of EGD prior to bariatric surgery is unclear. Studies have demonstrated routine EGD prior to bariatric surgery may diagnose foregut pathology; however, few of the findings alter the planned treatment. The cost effectiveness of this strategy is questionable. There are reports of EA developing after bariatric surgery; however, we found no previous case reports of EA identified at LRYGB. CONCLUSION: Our institution has opted for selective preoperative endoscopy in patients with preoperative gastrointestinal symptoms. In post gastric bypass patients LTHE can be performed with good results. PMID- 27379751 TI - Mountain bikes as seed dispersers and their potential socio-ecological consequences. AB - Seed dispersal critically influences plant community composition and species distributions. Increasingly, human mediated dispersal is acknowledged as important dispersal mechanism, but we are just beginning to understand the different vectors that might play a role. We assessed the role of mountain bikes as potential dispersal vectors and associated social-ecological consequences in areas of conservation concern near Freiburg, Germany. Seed attachment and detachment on a mountain bike were measured experimentally at distances from 0 to 500 m. We assessed effects of seed traits, weather conditions, riding distance and tire combinations using generalized linear mixed effect models. Most seeds detached from the mountain bike within the first 5-20 m. However, a small proportion of seeds remained on tires after 200-500 m. Attachment was higher, and the rate of detachment slower, in semi-wet conditions and lighter seeds travelled farther. Seed dispersal by mountain bikes was moderate compared to other forms of human mediated dispersal. However, we found that lighter seeds could attach to other bike parts and remain there until cleaning which, depending on riders' preferences, might only be after 70 km and in different habitats. Ecological impacts of mountain biking are growing with the popularity of the activity. We demonstrate that mountain bikes are effective seeds dispersers at landscape scales. Thus, management to mitigate their potential to spread non-native species is warranted. We suggest bike cleaning between rides, control of non-native species at trailheads and increased awareness for recreationalists in areas of conservation concern to mitigate the potential negative consequences of seed dispersal. PMID- 27379753 TI - (1)H-(14)N cross-relaxation spectrum analysis in sildenafil and sildenafil citrate. AB - Here we describe a method for the extraction of (14)N quadrupole parameters from a (1)H-(14)N cross-relaxation spectrum by fitting the lineshapes of the (14)N quadrupole transitions. The procedures used typically to fit quadrupole lineshapes are not directly applicable to fit the (1)H-(14)N cross-relaxation spectrum, because the presence of proton homonuclear dipolar interaction broadens the lineshapes considerably and prevents a reliable determination of Cq and eta from a single lineshape. Instead, one must fit two or even three lineshapes originating from the same nitrogen site simultaneously. The problem is to identify which lineshapes belong together when many are observed due to the existence of several nitrogen sites. We solve this problem by fitting the spectrum for all possible combinations and find the best-fitting one. This combination then most likely correctly identifies lineshapes belonging to the same nitrogen site. There are two main advantages of our method compared to the typically used method, which relies only on lineshape singularities: (i) the method is "automatic" and does not require knowledge of nitrogen quadrupole parameters in similar environments to aid dip pairing and (ii) the accuracy of quadrupole parameters is better, as proton linewidth is included in the fits. We use sildenafil and sildenafil citrate as model compounds, each with six non equivalent nitrogen sites. PMID- 27379752 TI - RAB25 expression is epigenetically downregulated in oral and oropharyngeal squamous cell carcinoma with lymph node metastasis. AB - Oral and oropharyngeal squamous cell carcinoma (OOSCC) have a low survival rate, mainly due to metastasis to the regional lymph nodes. For optimal treatment of these metastases, a neck dissection is required; however, inaccurate detection methods results in under- and over-treatment. New DNA prognostic methylation biomarkers might improve lymph node metastases detection. To identify epigenetically regulated genes associated with lymph node metastases, genome-wide methylation analysis was performed on 6 OOSCC with (pN+) and 6 OOSCC without (pN0) lymph node metastases and combined with a gene expression signature predictive for pN+ status in OOSCC. Selected genes were validated using an independent OOSCC cohort by immunohistochemistry and pyrosequencing, and on data retrieved from The Cancer Genome Atlas. A two-step statistical selection of differentially methylated sequences revealed 14 genes with increased methylation status and mRNA downregulation in pN+ OOSCC. RAB25, a known tumor suppressor gene, was the highest-ranking gene in the discovery set. In the validation sets, both RAB25 mRNA (P = 0.015) and protein levels (P = 0.012) were lower in pN+ OOSCC. RAB25 mRNA levels were negatively correlated with RAB25 methylation levels (P < 0.001) but RAB25 protein expression was not. Our data revealed that promoter methylation is a mechanism resulting in downregulation of RAB25 expression in pN+ OOSCC and decreased expression is associated with lymph node metastasis. Detection of RAB25 methylation might contribute to lymph node metastasis diagnosis and serve as a potential new therapeutic target in OOSCC. PMID- 27379754 TI - The Effect of Noise on Relationships Between Speech Intelligibility and Self Reported Communication Measures in Tracheoesophageal Speakers. AB - PURPOSE: The purpose of this study was to examine how sentence intelligibility relates to self-reported communication in tracheoesophageal speakers when speech intelligibility is measured in quiet and noise. METHOD: Twenty-four tracheoesophageal speakers who were at least 1 year postlaryngectomy provided audio recordings of 5 sentences from the Sentence Intelligibility Test. Speakers also completed self-reported measures of communication-the Voice Handicap Index 10 and the Communicative Participation Item Bank short form. Speech recordings were presented to 2 groups of inexperienced listeners who heard sentences in quiet or noise. Listeners transcribed the sentences to yield speech intelligibility scores. RESULTS: Very weak relationships were found between intelligibility in quiet and measures of voice handicap and communicative participation. Slightly stronger, but still weak and nonsignificant, relationships were observed between measures of intelligibility in noise and both self-reported measures. However, 12 speakers who were more than 65% intelligible in noise showed strong and statistically significant relationships with both self reported measures (R2 = .76-.79). CONCLUSIONS: Speech intelligibility in quiet is a weak predictor of self-reported communication measures in tracheoesophageal speakers. Speech intelligibility in noise may be a better metric of self-reported communicative function for speakers who demonstrate higher speech intelligibility in noise. PMID- 27379755 TI - Organic gunshot residues: Observations about sampling and transfer mechanisms. AB - This work aimed at studying the sampling, storage, transfer and persistence of organic gunshot residue (OGSR), mainly stabilizers, using liquid chromatography hyphenated to mass spectrometry. Collection using swabs and stubs was compared through sequential sampling in terms of amount of residues left on the hand of a shooter. While stubs collected nearly all residues, swabs left about 50% of the residues on the hands. Moreover, the study of storage conditions after sampling showed that stubs were more stable than swabs and could be held at room temperature without significant compound loss up to 2weeks. Then, shooting experiments were performed to evaluate transfer of OGSR. It was not possible to differentiate different brands of ammunition based on a single compound concentration. Moreover, a memory effect was identified when different ammunition was shot using the same firearm. Finally, various exposed skin surfaces and hair as well as clothing were sampled to estimate what surfaces might be the best targets for OGSR sampling by comparing results just after discharge and 2h after discharging a pistol. The results indicated that OGSR were more rapidly lost from hands than from clothing. Moreover, it was shown that the face and hair of a suspect might be contaminated through secondary transfer. Thus, OGSR might remain longer on other skin surfaces, hair and clothing than on the hands of a suspect. As a consequence, sampling should also include clothing, hair and face. PMID- 27379756 TI - Effect of mussel reproductive status on biomarker responses to PAHs: Implications for large-scale monitoring programs. AB - Biomarkers are useful tools to assess biological effects of pollutants and have been extensively used in monitoring programs to determine ecosystem health. In these programs, a wide range of environmental conditions are covered and sometimes, obtained data are difficult to interpret because of natural variables are affecting biomarker responses. Among these variables, mussels reproductive status has been considered one of the most changing variables between sites in a monitoring survey. Thus, the main aim of this work was to identify the effect that mussel reproductive status has on biomarker responses. For that purpose, mussels sampled at two periods in the reproductive cycle (reproductive and resting stages) were conditioned to the same laboratory conditions and exposed to fluoranthene (FLU) for three weeks. Studied biomarkers covering a wide range of organism responses were included: bioaccumulation, physiological rates (clearance rate -CR-, absorption efficiency -AE-, respiration rate -RR- and their integration in the scope for growth -SFG-), antioxidant enzyme activities (superoxide-dismutase -SOD-, catalase -CAT-, glutathione reductase -GR-, glutathione peroxidase -GPx-, glutathione-S-tranferase -GST-) and biochemical damage responses (lipid membrane peroxidation -LPO-). The results obtained evidenced that the levels of the biomarkers studied (RR, SOD, CAT and GPx) were higher at reproductive than at resting stage. On the other hand, the effect of toxicant was observed in SFG, CAT and GPx but this effect was only detected during the resting period. Moreover, there was a deterioration of mussel gonadal tissue with FLU exposure during reproductive stage. FLU accumulation in mussel tissues was also dependent of the reproductive status with higher internal concentrations during resting than reproductive period. In conclusion, there was a strong effect of reproductive status on studied biomarkers which seems to mask the effect of FLU at reproductive stage. The present study evidences the need to include the measurement of mussel biological status in marine pollution monitoring programs for a correct interpretation of biomarker data. PMID- 27379757 TI - Abstracts from the 31st Annual Meeting of the Engineering and Urology Society May 7, 2016 San Diego, CA. PMID- 27379758 TI - Female Colour Polymorphism and Unique Reproductive Behaviour in Polythore Damselflies (Zygoptera: Polythoridae). AB - We studied Polythore damselflies by mark-recapture techniques in the Jatun Sacha Biological Reserve (Ecuador) for a period of 48 days in October-December 2014. Three species were found: Polythore mutata (MacLachlan) was the commonest species (111 individuals marked), Polythore derivata (MacLachlan) was rare (24 individuals) and Polythore concinna (MacLachlan) occasional (four individuals). In P. mutata, we found two phenotypes amongst females, one of them with a white band on the wings, very similar in colouration to the conspecific male (androchrome), and the other with an amber band (gynochrome). The recapture of marked females indicates that both phenotypes are maintained since emergence to maturation and are not age-related (i.e. polymorphism). Androchromes represent 40% of females observed. The colour of the wing band showed an age-dependent change in size with opposite trends between sexes, increasing in males and decreasing in females. Males and females were observed to return to the same forest locations in different days. Courtships and ovipositions involving androchrome females were not observed. No matings were observed in any morph. In contrast, we recorded two consecutive matings of one female P. derivata. We found that Polythore males grasp the mesothorax of females during mating instead of the prothorax as in other Zygoptera. We discuss the rarity of reproductive behaviour in this genus and how female morphs might be maintained. PMID- 27379759 TI - Biological Strategies of Dermestes maculatus DeGeer (Coleoptera: Dermestidae) at Larval Stages in Different Temperatures. AB - The intraspecific variation in larval instars is a widely distributed phenomenon amongst holometabolous insects. Several factors can affect the number of instars, such as temperature, humidity, and density. Only a few references could be found in the literature because the invariability in the number of larval instars is considered normal, and the issue has raised little to no interest. Despite this, no study to date has intended to assess or focus on the larval development. Here, we analyzed the effect of different rearing temperature on the larval stage of Dermestes maculatus DeGeer (Coleoptera: Dermestidae). The results indicated that at all temperatures, L5 represented a decisive point for individuals as well as the other later larval instars, because the next step to follow was to pupate or molt to the next larval instar. Furthermore, there were mainly two populations, L5 and L6, although in different proportions according to temperature. We also found that at a greater number of instars, the larval development at all temperatures lasted longer. Moreover, the exponential model was the best adjustment in the developmental time of all populations as well as for the accumulated developmental time of L1-L4. Thus, we conclude that random factors such as genetics could probably cause interspecific variability in D. maculatus larval development. PMID- 27379760 TI - Toxicity of Secondary Metabolites from Meliaceae Against Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae). AB - The study was carried out to evaluate the bioactivity of secondary metabolites from Trichilia pallida, Trichilia pallens, and Toona ciliata against fall armyworm Spodoptera frugiperda (J. E. Smith) larvae. The studied compounds included (+/-)-catechins, a triglyceride, and cedrelone isolated from T. ciliata branches, fruits, and stems, respectively; dammaradienol isolated from T. pallida leaves; and scopoletin isolated from T. pallens branches. The compounds' activity was evaluated through ingestion and topic treatment. Treated artificial diet was offered to first instar larvae to evaluate ingestion effect, while an application on the dorsal thoracic region of third instar larvae was used to evaluate the topic effect. Mortality was assessed daily, and larval weight was recorded after 7 days for ingestion and 5 days for topic application. Scopoletin and triglyceride caused low mortality rates and reduction in larval weight by ingestion, (+/-)-catechins caused larval weight reduction by ingestion, and scopoletin reduced survival by topic treatment. The most effective compound was cedrelone that affected larval survival and development mainly by ingestion. The estimated LC50, LC90, and EC50 for cedrelone were 0.0365, 0.0659, and 0.0095%, respectively. Further, cedrelone-treated corn leaf discs were offered to fourth instar larvae during 16 h in choice and no-choice tests. The deterrence indexes obtained in the choice tests were 23.5 and 36.3% at concentrations of 0.0365 and 0.0659, respectively. Consumption of cedrelone-treated leaf discs at the concentration of 0.0659% was lower compared to the control in the no-choice test. Thus, cedrelone caused lethal and sublethal effects and phagodeterrence on S. frugiperda and should be further studied. PMID- 27379761 TI - Chemical Composition of the Low-Polar Fraction of the Copitarsia uncilata Burgos & Leiva (Lepidoptera: Noctuidae) Eversible Pheromone Gland. AB - In Colombia, Copitarsia uncilata Burgos & Leiva has been reported as a pest of ornamental flowers. The leafworm causes serious economic losses to farmers because the shipments are intercepted at the detection sites. The identification and subsequent synthesis of the sex pheromone compounds can lead to the use of semiochemicals as an important strategy to complement the pest management. This paper identifies and characterizes the chemical components of the female sexual gland of C. uncilata at three different age stages in order to relate the effect of age on the gland extract composition. Eggs and larvae were collected from commercial crops. The specimens were reared and sexed. Pheromone glands of intact females were excised at (a) 1-2, (b) 3-4, and (c) 5-6 days old. The extracts were analyzed using GC-MS after two extraction time points: 20 min and 8 days. The extracts from the third age stage showed an increase in concentration for 35% of the compounds after 8 days of storage. The relative abundance as a function of the female age showed two trends: an upward trend, where the relative abundances of the compounds increased through the age stages, while some compounds shown a downward trend. Within the first trend, mostly of the compounds were found to be related with infochemicals type structures, where tetradec-9-en-1-yl acetate (within several C-14 long-chain alcohols) is the main one. The 9-14:Ac quadrupled concentration through the ages is possibly related to the increased length of calling period as female moth age. PMID- 27379762 TI - Prevalence, severity, and clinical features of acute and chronic pancreatitis in patients with systemic lupus erythematosus. AB - Pancreatitis is a rare, life-threatening complication of systemic lupus erythematosus (SLE). This study aimed to describe the clinical features of acute pancreatitis (AP) and chronic pancreatitis (CP) in patients with SLE. Data of patients who fulfilled the revised criteria of the American Rheumatism Association for diagnosis of SLE were retrospectively analyzed. SLE activity was graded according to the SLE Disease Activity Index. Logistic regression analysis was conducted to find out independent associations. Survival rates were estimated by using Kaplan-Meier plots. This study included 5665 SLE patients admitted between January 1983 and January 2014, of whom 52 patients were diagnosed with pancreatitis. Pancreatitis prevalence in SLE patients was 0.92 % (52/5665). AP (0.8 %, 46/5665) was more prevalent than CP (0.1 %, 6/5665), presented mostly during active SLE, and affected more organs. Hypertriglyceridemia occurred in 76.9 % of AP patients and in none of the CP patients. AP patients were divided into severe (n = 10) or mild (n = 20) cases. The average triglyceride level in severe AP cases was higher than that in mild AP cases (P = 0.006), and the mortality rate of lupus-associated AP was 32.6 % (15/46). Concomitant infections and thrombocytopenia were independently associated with poor prognosis (P < 0.001, P = 0.028, respectively). There were significant differences in the clinical manifestations of AP and CP. Patients with severe AP were found to have a higher incidence of concomitant infection and serum triglyceride levels. Concomitant infections and thrombocytopenia were independent risk factors for poor prognosis. PMID- 27379764 TI - Association of the ATIC 347 C/G polymorphism with responsiveness to and toxicity of methotrexate in rheumatoid arthritis: a meta-analysis. AB - This study investigated whether the 5-aminoimidazole-4-carboxamide ribonucleotide transformylase gene (ATIC) 347 C/G polymorphism can predict the response to or toxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA). We conducted a meta-analysis of studies on the association between ATIC 347 C/G polymorphism and non-responsiveness to or toxicity of MTX in RA patients, using PUBMED, EMBASE, and COCHRANE. Nine comparative studies from 6 articles including 1056 RA patients met our inclusion criteria. This final group of studies comprised 5 studies on response to MTX and 4 on toxicity of MTX in RA patients in relation to the ATIC 347 C/G polymorphism status. Meta-analysis showed association between the ATIC 347 GG + GC genotype and non-response to MTX therapy (OR = 1.572, 95 % CI 1.146-2.156, p = 0.005). Stratification by ethnicity indicated significant association between the ATIC 347 GG + GC genotype and non response to MTX in Caucasians (OR = 1.884, 95 % CI 1.236-2.873, p = 0.003), but not in Asian patients. Similarly, associations were noted for the ATIC 347 C/G polymorphism through analysis using recessive and overdominant models. Meta analysis revealed association between the ATIC 347 GG + GC genotype and MTX toxicity (OR = 1.454 95 % CI 1.034-2.044, p = 0.032). Stratification by ethnicity indicated significant association between the ATIC 347 GG + GC genotype and MTX toxicity in Caucasians (OR = 1.741, 95 % CI 1.080-2.806, p = 0.023), but not in Asian patients. The ATIC 347 C/G polymorphism may be associated with non responsiveness to and or toxicity of MTX in Caucasian RA patients. PMID- 27379766 TI - [Not Available]. PMID- 27379763 TI - Spinal fractures in patients with ankylosing spondylitis. AB - The ankylosed spine is prone to fracture even after minor trauma due to its changed biomechanical properties. The two central features of ankylosing spondylitis (AS) that promote the pathological remodeling of the spine are inflammation and new bone formation. AS is also associated with osteoporosis that is attributed to an uncoupling of the bone formation and bone resorption processes. Therefore, bone resorption occurs and promotes weakening of the spine as well as increased risk of vertebral fractures which can be hugely different in terms of clinical relevance. Even in the presence of symptomatic clinical vertebral fractures, the diagnosis can be overruled by attributing the pain to disease activity. Furthermore, given the highly abnormal structure of the spine, vertebral fracture diagnosis can be difficult on the basis of radiography alone. CT can show the fractures in detail. Magnetic resonance imaging is considered the method of choice for the imaging of spinal cord injuries, and a reasonable option for exclusion of occult fractures undetected by CT. Since it is equally important for radiologists and clinicians to have a common knowledge base rather than a compartmentalized view, the aim of this review article was to provide the required clinical knowledge that radiologists need to know and the relevant radiological semiotics that clinicians require in diagnosing clinically significant injury to the ankylosed spine. PMID- 27379767 TI - [Not Available]. PMID- 27379765 TI - Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1. AB - PURPOSE: Loss and gain-of-function (GOF) mutations in human signal transducer and activator of transcription 1 (STAT1) lead to distinct phenotypes. Although recurrent infections are common to both types of STAT1 mutations, GOF mutations are distinguished by chronic mucocutaneous candidiasis and autoimmunity. However, the clinical spectra of STAT1 GOF mutations continue to expand. We here describe two patients with STAT1 GOF mutations presenting early in life with combined immunodeficiency (CID). METHODS: Clinical data and laboratory findings including immunophenotyping, level of interferon (IFN)-gamma/IL-17(+) T cells, interferon induced STAT1 phosphorylation, and JAK inhibitor assays were evaluated. Sequencing of STAT1 gene was performed by Sanger sequencer. RESULTS: Patient 1 (P1) had persistent oral candidiasis and cytomegalovirus (CMV) infection since 2 months of age and later developed cavitary lung lesions due to Mycobacterium tuberculosis. Patient 2 (P2) presented with oral candidiasis and recurrent pneumonia at 4 months of age and subsequently developed CMV pneumonitis. Both patients suffered heterozygous missense mutations in STAT1, leading to deleterious amino acid substitutions in the DNA binding domain (P1: c.1154C > T; p.T385M; P2. c.971G > T; p.C324F). Circulating CD4(+) T cells of both patients exhibited increased interferon-gamma and decreased IL-17 expression as compared to controls. They also exhibited increased IFN-beta and -gamma-induced STAT1 phosphorylation that was reversed upon treatment with the JAK kinase inhibitor ruxolitinib. CONCLUSION: STAT1 GOF mutations may present early in life with CID, consistent with the clinical heterogeneity of the disease. JAK kinase inhibitors may potentially be useful in some patients as adjunct therapy pending definitive treatment with bone marrow transplantation. PMID- 27379768 TI - [Not Available]. PMID- 27379769 TI - Physical Fitness and Body Composition Two Years after Roux-En-Y Gastric Bypass in Adolescents. AB - BACKGROUND: We have previously shown promising results 2 years after Roux-en-Y gastric bypass surgery, within the Adolescence Morbid Obesity Surgery study (AMOS). The aim of the current study was to describe the 2-year outcome in cardiorespiratory fitness, body composition, and functional capacity in the Stockholm subset of the AMOS study. METHODS: Forty-one adolescents (10 male, 31 female, age 14-18 years, body mass index 35-69 kg.m-2) were included. In addition to anthropometric measurements, participants performed a submaximal bicycle test, 6-min walk test, dual-energy X-ray absorptiometry, and a short interview at baseline, 1 and 2 years after surgery. RESULTS: Relative improvements in maximal oxygen consumption (VO2max) per kilogram body mass (+62 %) and per kilogram fat free mass (+21 %), as well as walking distance (+13 %) were observed after 1 year, and persisted 2 years after surgery. Despite a reduction of fat-free mass ( 15 %), absolute VO2max was maintained across the full group (+8 %, p = ns) and significantly increased in non-smokers. Body mass and fat mass were significantly decreased (-45.4 and -33.3 kg, respectively). Self-reported physical activity was significantly increased, and pain associated with movement was reduced. CONCLUSIONS: In adolescents with obesity, Roux-en-Y gastric bypass improved VO2max more than could be explained by fat mass loss alone. In combination with improved functional capacity and body composition, these results suggest that surgery in adolescence might add specific benefits of importance for future health. PMID- 27379770 TI - Laparoscopic Sleeve Gastrectomy With or Without Staple Line Inversion and Distal Fixation to the Transverse Mesocolon: Impact on Early Postoperative Outcomes. AB - BACKGROUND AND AIM: Staple line complications and axial rotation of the gastric tube after sleeve gastrectomy are well-recognized complications of the procedure. The present study aims to investigate the role of staple line inversion and distal fixation to the transverse mesocolon in reducing these complications. PATIENTS AND METHODS: This is a retrospective analysis of prospectively collected data of 252 patients with morbid obesity who underwent laparoscopic sleeve gastrectomy (LSG). Patients were subdivided into two groups: group I comprising 124 patients did not have distal sleeve fixation and group II comprising 128 patients underwent staple line inversion and distal fixation. RESULTS: Patients were 171 females and 81 males with a mean age of 33.2 +/- 8.7 years and a mean preoperative body mass index (BMI) of 50.9 +/- 8.6 Kg/m2. The mean operating time was 103.9 +/- 26.9 min and the median hospital stay was 1 day. Major complications were detected in 15 (5.9 %) patients, who were all in group I. Group I had significantly shorter operative time and significantly higher rates of staple line bleeding (4 % in group I versus 0 in group II) and gastric axial rotation (5.6 % in group I versus 0 in group II). There were no significant differences between the two groups regarding early postoperative vomiting (21.7 % versus 26.5 %) and staple line leak (2.4 % versus 0). CONCLUSION: Staple line inversion and distal fixation to the transverse mesocolon can be a simple, effective strategy to prevent staple line bleeding, and gastric axial rotation, though it prolonged the operative time of LSG. PMID- 27379771 TI - Evidence for a role for the putative Drosophila hGRX1 orthologue in copper homeostasis. AB - Glutaredoxins are a family of small molecular weight proteins that have a central role in cellular redox regulation. Human GRX1 (hGRX1) has also been shown to play an integral role in copper homeostasis by regulating the redox activity of the metalated sites of copper chaperones such as ATOX1 and SOD1, and the copper efflux proteins ATP7A and ATP7B. To further elucidate the role of hGRX1 in copper homeostasis, we examined the impact of RNA interference-mediated knockdown of CG6852, a putative Drosophila orthologue of hGRX1. CG6852 shares ~41 % amino acid identity with hGRX1 and key functional domains including the metal-binding CXXC motif are conserved between the two proteins. Knockdown of CG6852 in the adult midline caused a thoracic cleft and reduced scutellum, phenotypes that were exacerbated by additional knockdown of copper uptake transporters Ctr1A and Ctr1B. Knockdown of CG6852 in the adult eye enhanced a copper-deficiency phenotype caused by Ctr1A knockdown while ubiquitous knockdown of CG6852 resulted a mild systemic copper deficiency. Therefore we conclude that CG6852 is a putative orthologue of hGRX1 and may play an important role in Drosophila copper homeostasis. PMID- 27379772 TI - De Barsy syndrome type B presenting with cardiac and genitourinary abnormalities. PMID- 27379773 TI - Metabolism of Pyrithiobac Sodium in Soils and Sediment, Addressing Bound Residues via Kinetics Modeling. AB - Degradation of pyrithiobac sodium (PE350) was examined in a number of soils and sediments using (14)C-PE350. It degrades primarily via microbial degradation which leads to the separation of the two rings of the molecule. Identification of several metabolites, many of which were minor products, helped to understand the formation of nonextractable residues (NER) and (14)CO2. In all studies, unextractable residues accounted for a large portion (20-60%) of the residues. Traditional kinetics modeling treats NER and CO2 as a single compartment, stated as sink, and formation mechanism of such components individually is ignored. Since studies conducted with radiolabeled test substance provides an accurate measurement of NER and CO2, we have demonstrated that kinetics modeling with these compartments separately can be used to clarify degradation pathways, including the origin of NER and CO2. This work demonstrated that overall metabolism in soils and sediments proceeded via similar pathways, and kinetics modeling was useful in clarifying the degradation route and formation of NER in all studies. PMID- 27379775 TI - [Extracorporeal lung support-news and future developments]. AB - Technical developments as well as the experiences during the 2009 influenza pandemia have led to an increased and safer use of extracorporeal gas exchange. Indications are expanding as new systems with the main goal of CO2 elimination have entered the market, thus, broadening the range of systems in addition to classic "high flow" extracorporeal membrane oxygenation (ECMO), although evidence for many suggested indications is sparse or lacking. However, recent research has shed light into the pathophysiology and interaction between the organism and the extracorporeal systems. Upcoming indications like avoiding intubation and mechanical ventilation or reducing invasiveness of ventilation are being evaluated. Novel data and technical advances will keep perspectives of extracorporeal gas exchange dynamic and exciting. PMID- 27379778 TI - [Not Available]. PMID- 27379776 TI - Low intensity laser and LED therapies associated with lateral decubitus position and flexion exercises of the lower limbs in patients with lumbar disk herniation: clinical randomized trial. AB - The objective of this study is to evaluate the effectiveness of laser and LED therapies, associated with lateral decubitus position and flexion exercises of the lower limbs in patients with lumbar disk herniation (LDH). It is a randomized blinded clinical trial. Fifty-four subjects with LDH L4-L5 and L5-S1 were selected and randomly allocated into groups: laser 904 nm, placebo, and LED 945 nm. The numbers of subjects for each group that completed the treatment were 18, 13, and 18, respectively. Twelve points over the lumbar spine region (L2 to S1) and eight points on the injured thigh in the path of the lumbar roots L5 and S1 were irradiated. Irradiation parameters for each point were as follows: laser wavelength 904 +/- 10 nm, average power 0.038 +/- 20 % W, irradiated area 0.16 cm(2), energy per point 4 J, and treatment time per point 104 s; LED wavelength 945 +/- 15 nm, power 0.1 W, irradiated area 1.0cm(2), energy per point 4 J, and treatment time per point 40 s. Lateral decubitus opposite to the side of the radicular was the standard position for all patients. After phototherapy and laser placebo sessions, the subjects performed sequences of flexion exercises of the lower limbs (ten per session) for 15 daily sessions. VARIABLES STUDIED: pain intensity assessed by visual analog scale (VAS), degree of flexion of the affected hip measured by the universal goniometer and functional capacity assessed by the Oswestry Disability Index. The three groups had statistically significant improvement in lumbar and radicular pain, in hip mobility, and in the functional disability index (p <= 0.001). There was a statistically significant difference (p = 0.024) in radicular pain between the groups, gait claudication and Oswestry Disability Index. We can conclude that in the treatment of L4-L5 and L5-S1 LDH with radiculopathy, LED, associated with lateral decubitus position and flexion exercises of the lower limbs, showed better therapeutic performance for radicular pain, gait claudication, and functional disability. PMID- 27379779 TI - [Not Available]. PMID- 27379777 TI - Online tobacco websites and online communities-who uses them and do users quit smoking? The quit-primo and national dental practice-based research network Hi Quit studies. AB - Online tobacco cessation communities are beneficial but underused. Our study examined whether, among smokers participating in a web-assisted tobacco intervention (Decide2quit.org), specific characteristics were associated with navigating to BecomeAnEx.org, an online cessation community, and with subsequent quit rates. Among smokers (N = 759) registered with Decide2quit.org, we identified visitors to BecomeAnEx.org, examining associations between smoker characteristics and likelihood of visiting. We then tested for associations between visits and 6-month cessation (point prevalence). We also tested for an interaction between use of other online support-seeking (Decide2quit.org tobacco cessation coaches), visiting, and 6-month cessation. One quarter (26.0 %; n = 197) of the smokers visited BecomeAnEx.org; less than one tenth (7.5 %; n = 57) registered to participate in the online forum. Visitors were more likely to be female (73.0 vs. 62.6 % of non-visitors, P < 0.01) to have visited a cessation website before (33.0 vs. 17.4 %, P < 0.01) and to report quit attempts in the previous year (62.0 vs. 53.0 %, P = 0.03). In analyses of all participants, BecomeAnEx.org visiting was not associated with 6-month quit completion. Among participants who communicated with a coach, BecomeAnEx.org visiting also lacked a significant association with 6 month quit completion, although a non-significant trend toward quit completion in visitors was noted (OR 2.21, 95 % CI 0.81-3.1). Online cessation communities attract smokers with previous cessation website experience and recent quit attempts. Community visiting was not associated with quit rates in our study, but low use may have limited our power to detect differences. Further research should explore whether an additive effect can be achieved by offering community visitors support via online coaches. PMID- 27379780 TI - Tissue Bioengineering in the Treatment of Osteochondritis Dissecans of the Talus in Children With Open Physis: Preliminary Results. AB - BACKGROUND: Juvenile osteochondritis dissecans of the talus (JOCDT) is a focal idiopathic lesion primarily of the subchondral bone leading to subsequent cartilaginous damage. The majority of the papers dealing with JOCDT reported heterogeneous case studies of patients treated with different cartilage repair techniques. The purpose of this paper is to retrospectively review both clinical and radiologic results among 7 patients affected by JOCDT treated with arthroscopic bone marrow aspirate concentrate (BMAC) transplantation with the 1 step technique. METHODS: Both standard anterior-posterior and lateral radiographs and a 1.5 T magnetic resonance imaging of the affected ankle were preoperatively performed in all the patients. The American Orthopaedic Foot and Ankle Society (AOFAS) score and the visual analogue scale were administered to the patients preoperatively and at the final follow-up. RESULTS: Patients were followed up to an average of 48.1+/-18.4 months. According to the Berndt and Harty classification, 6 lesions were found to be in stage III and 1 lesion in stage IV. The average preoperative AOFAS score was 58.8+/-7.6 points. At the mean follow-up of 48.1 months the average AOFAS score improved to 95.7+/-5.4 points (P<0.05). Visual analogue scale improved from 6.3 preoperatively to 0.4 at final follow-up (P<0.05). Complete radiographic healing, in terms of complete bony filling, was observed in 3 of 7 cases. The magnetic resonance imaging analysis showed a complete filling of the osteochondral defect in 4 patients, whereas in 1 patient a hypotrofic tissue was observed. CONCLUSIONS: BMAC transplantation is able to provide good to excellent results in the treatment of JOCDT. The 43% of our patients showed a complete radiographic healing, but all the patients were satisfied with the procedure. Because of the rareness of the lesion, further studies involving more patients and with a longer follow-up are required, to establish the advantage of performing a regenerative procedure like the BMAC transplantation in a pediatric population. LEVEL OF EVIDENCE: Level IV. PMID- 27379781 TI - Treatment of the Dislocated Hip in Infants With Spasticity. AB - BACKGROUND: Although many studies have separately investigated the treatment of developmental dysplasia of the hip and spastic hip disease, little data exist regarding the treatment of infants with dislocated hips and underlying spasticity. The purpose of this study was to review our results after the surgical treatment of these infants. METHODS: We retrospectively reviewed all children below 3 years of age who underwent hip reconstruction for dislocated hips in the setting of cerebral palsy or other spastic/high-tone neuromuscular disease. Medical records were reviewed for clinical data including treatment course, complications, and need for further surgery. Preoperative and postoperative radiographs were used to determine International Hip Dysplasia Institute (IHDI) grade of dislocation, acetabular index, migration percentage, and presence of avascular necrosis according to the Salter criteria. RESULTS: Eleven patients with 15 hips met our inclusion criteria with a mean age of 20+/-8 (range, 6 to 34) months. Preoperatively, 12 of 15 hips (80%) were IHDI grade 4 and 3 of 15 (20%) were IHDI grade 3. Mean acetabular index was 29+/-8 (range, 19 to 46) degrees. Patients underwent open reduction (15 hips), adductor tenotomy (14 hips), femoral osteotomy (10 hips), and pelvic osteotomy (12 hips). At a mean follow-up of 40+/-16 (range, 13 to 71) months, 13 of 15 hips were IHDI grade 1 (86.7%), 1 was IHDI grade 2 (6.7%), and 1 hip was IHDI grade 3 (6.7%). The mean postoperative migration index was 7%+/-24% (range, -30% to 46%); the mean acetabular index was 22+/-8 (range, 9 to 38) degrees. No patients developed radiographically significant osteonecrosis. Complications included 2 femur fractures (13.3%) and 1 symptomatic implant that required early removal. One patient underwent further reconstructive hip surgery. CONCLUSIONS: In this series of infants with hip dislocations and underlying spasticity, open reduction+/ pelvic osteotomy and/or femoral osteotomy has a nearly 90% success rate in achieving and maintaining adequate hip reduction at intermediate-term follow-up. In the unique population of infants with dislocated hips and underlying spasticity, comprehensive hip reconstruction is largely successful with an acceptable rate of complications. LEVEL OF EVIDENCE: Level IV-retrospective. PMID- 27379782 TI - Introduction to Evidence-based Recommendations for Pediatric Orthopaedic Practice. PMID- 27379783 TI - Mid-term Results of Femoral and Tibial Osteotomies and Fassier-Duval Nailing in Children With Osteogenesis Imperfecta. AB - BACKGROUND: Patients with osteogenesis imperfecta (OI) have significant burden of both fractures and bony deformities. The present approach to care in this disorder is a combination of surgical care with intramedullary rod fixation, cyclic bisphosphonate therapy, and rehabilitation with goal of maximizing patient function and quality of life. METHODS: Retrospective chart review identified 58 children with OI who had realignment osteotomies with Fassier-Duval (FD) intramedullary nailing of the lower extremity by a single surgeon. This is a consecutive series treated between 2003 and 2010. Postoperatively, patients were followed up clinically and radiologically. Motor function was assessed using the Brief Assessment of Motor Function score and the walking scale subset of the Gillette Functional Assessment Questionnaire. RESULTS: Fifty-eight patients had 179 lower extremity FD intramedullary rods placed. This technique allowed for intervention on multiple long bones, with 29% having bilateral femur and tibial rodding in the same procedure. Revisions were required in 53% of patients, which occurred at a mean time of 52 months after initial rodding surgery. In most cases, revision surgery was related to patient growth and subsequent fracture, although rod migration did occur in a minority of patients. Nonunion or incomplete union was 14.5% in this series. Bisphosphonate infusion was not postponed after surgical procedures. Patients had improvement in mobility status at the latest follow-up. CONCLUSIONS: This series lends evidence to the medium term utility of FD intramedullary rods as an effective and less invasive platform for stabilization and correction of deformity in long bones of patients with OI. Relatively low blood loss and relatively short hospitalizations were noted. Nonunion rate was comparable with existing literature noting that our patients did not have postsurgical postponement of bisphosphonate therapy. LEVEL OF EVIDENCE: Therapeutic study to investigate the results of treatment with FD rods. Retrospective case series model of Level IV evidence quality. PMID- 27379784 TI - Management of Scoliosis in Patients With Loeys-Dietz Syndrome. AB - BACKGROUND: Loeys-Dietz syndrome (LDS) is a genetic connective tissue disorder. We sought to determine the incidence of scoliosis in patients with LDS, characterize the spectrum of spinal deformity, determine the results of bracing and surgery, and define surgical complications. METHODS: Patients were selected from our institution's database of 183 patients with LDS. Imaging measurements were performed for 141 patients whose records permitted spinal evaluation. Deformity changes and complications after intervention were recorded for patients who underwent bracing or surgery, and associations were tested using Student t tests (significance, P<0.05). RESULTS: Eighty-eight of 141 (62%) patients with LDS had scoliosis, with main thoracic and thoracolumbar curves being most common. Fifteen patients were braced (mean age, 9+/-3 y) for a mean of 2.3 years. They had a mean postbracing curve progression of 12+/-21 degrees (5+/-9 deg./y). There were no significant differences in age, sex, curve type, or prebracing curve magnitude between successfully braced (n=4) and unsuccessfully braced (n=11) patients (P>0.05). Nine patients, (mean age, 12+/-3 y), underwent 24 surgical procedures (16 growing rod procedures, 8 fusions). Mean curve corrections were 61% for growing rods and 73% for fusions. Associated blood loss for these procedures was 400 mL and 1293 mL, respectively, and normalized blood loss for fusion was 2.34 mL/kg/level. Fifteen of 24 surgical procedures involved complications (63%), including cerebrospinal fluid leaks (n=7) and blood loss >20% of estimated total blood volume (n=11). CONCLUSIONS: Scoliosis was present in 62% of our sample of LDS patients. Bracing did not halt curves in 11 of 15 patients, whose curves progressed >5 degrees or to >50 degrees by completion of bracing. At latest follow-up, 47% of the braced patients had undergone surgery after prior bracing attempts. The high blood loss associated with these operations is believed to be related to vascular fragility in patients with LDS. LEVEL OF EVIDENCE: Level IV-retrospective cohort study. PMID- 27379785 TI - How Many Patients Who Have a Clubfoot Treated Using the Ponseti Method are Likely to Undergo a Tendon Transfer? AB - BACKGROUND: The Ponseti method has become the standard of care for the treatment of idiopathic clubfoot. A commonly reported problem encountered with this technique is a relapsed deformity that is sometimes treated in patients older than 2.5 years by an anterior tibial tendon transfer (ATTT) to the third cuneiform. Presently, there is insufficient information to properly counsel families whose infants are beginning Ponseti treatment on the probability of needing later tendon transfer surgery. METHODS: All idiopathic clubfoot patients seen at the authors' institution during the study period who met the inclusion criteria and who were followed for >2.5 years were included (N=137 patients). Kaplan-Meier Survival analysis was used to determine the probability of survival without the need for ATTT surgery. In addition, the influence of patient characteristics, socioeconomic variables, and treatment variables on need for surgery was calculated. RESULTS: On the basis of the survivorship analysis, the probability of undergoing an ATTT remained below 5% for all patients at 3 years of age, but exceeded 15% by 4 years of age, increasing steadily afterwards such that by 6 years of age, the probability of undergoing an ATTT reached 29% of all patients. Overall, controlling for all other variables in the analysis, parent reported adherence with bracing reduced the odds of undergoing surgery by 6.88 times, compared with parent-reported nonadherence (P<0.01). CONCLUSIONS: This is the first study to report the probability of undergoing ATTT surgery as a function of age using survivorship analysis following Ponseti clubfoot treatment. Although the overall probability reached 29% at 6 years, this was significantly reduced by compliance with bracing. This information may be useful to the clinician when counseling families at the start of treatment. LEVEL OF EVIDENCE: Level III-theraputic. PMID- 27379786 TI - Predicting Postsurgical Satisfaction in Adolescents With Idiopathic Scoliosis: The Role of Presurgical Functioning and Expectations. AB - BACKGROUND: There is a need to better assess patient satisfaction and surgical outcomes. The purpose of the current study is to identify how preoperative expectations can impact postsurgical satisfaction among youth with adolescent idiopathic scoliosis undergoing spinal fusion surgery. METHODS: The present study includes patients with adolescent idiopathic scoliosis undergoing spinal fusion surgery enrolled in a prospective, multicentered registry examining postsurgical outcomes. The Scoliosis Research Society Questionnaire-Version 30, which assesses pain, self-image, mental health, and satisfaction with management, along with the Spinal Appearance Questionnaire, which measures surgical expectations was administered to 190 patients before surgery and 1 and 2 years postoperatively. Regression analyses with bootstrapping (with n=5000 bootstrap samples) were conducted with 99% bias-corrected confidence intervals to examine the extent to which preoperative expectations for spinal appearance mediated the relationship between presurgical mental health and pain and 2-year postsurgical satisfaction. RESULTS: Results indicate that preoperative mental health, pain, and expectations are predictive of postsurgical satisfaction. CONCLUSIONS: With the shifting health care system, physicians may want to consider patient mental health, pain, and expectations before surgery to optimize satisfaction and ultimately improve clinical care and patient outcomes. LEVEL OF EVIDENCE: Level I-prognostic study. PMID- 27379787 TI - Complications After Plate Fixation of Displaced Pediatric Midshaft Clavicle Fractures. AB - BACKGROUND: Operative treatment of displaced pediatric midshaft clavicle fractures has become increasingly popular, despite lack of evidence that surgical management leads to superior outcomes. Complications, such as plate irritation necessitating removal and wound infection, have been reported in adults. The purpose of this study was to evaluate complications after plate fixation of midshaft clavicle fractures in the pediatric population. METHODS: We retrospectively identified patients 10 to 18 years old who had undergone plate fixation of a displaced midshaft clavicle fracture between 2009 and 2014. Patients who had surgery for a malunion or nonunion, and patients with <6 months of follow-up were excluded. Demographic data, radiographic union, time to return to activity, and complications were recorded. Any complication that led to unplanned surgery was considered a major complication. RESULTS: We analyzed 36 patients (25 males, 11 females) with 37 fractures. The average age at surgery was 14.5+/-1.7 years and mean follow-up was 1.3+/-1.0 years. All of the fractures healed and average time to return to activity was 58+/-28 days. The overall postoperative complication rate was 86% (32/37): 59% (22/37) implant prominence or irritation, 16% (6/37) anterior chest wall numbness, 5% (2/37) superficial wound dehiscence or infection, 3% (1/37) refracture adjacent to the plate, and 3% (1/37) refracture after implant removal. The major complication rate was 43% (16/37). Fifteen patients underwent a second surgery for implant removal secondary to prominence or pain. One patient underwent revision open reduction and internal fixation after he sustained a refracture at the distal aspect of the plate that resulted in a painful nonunion. Only 1 patient had a refracture after implant removal and this was treated nonoperatively. CONCLUSIONS: Implant prominence or irritation is common after plate fixation of displaced pediatric midshaft clavicle fractures. A second surgery for implant removal may be necessary. Patients should be appropriately counseled regarding complications before plate fixation of midshaft clavicle fractures. LEVEL OF EVIDENCE: Level IV therapeutic. PMID- 27379788 TI - Comparison of Allograft and Bovine Xenograft in Calcaneal Lengthening Osteotomy for Flatfoot Deformity in Cerebral Palsy. AB - BACKGROUND: The Evan's calcaneal lengthening osteotomy is a treatment method for spastic flatfoot deformity in patients with cerebral palsy that fail nonoperative measures. Autograft and allograft have been reported as potential graft choices. Bovine xenograft has been introduced as an alternative, but limited human data exists supporting its efficacy. This study compares the long-term results of allograft versus xenograft in isolated Evan's procedure performed for correction of flexible spastic flatfoot deformity. METHODS: This retrospective study accessed charts of 4- to 18-year-olds diagnosed with cerebral palsy who received an Evan's procedure. Preoperative and postoperative radiographic measurements (lateral calcaneal pitch, lateral talocalcaneal, lateral talo-first metatarsal, anteroposterior talonavicular coverage, anteroposterior talo-first metatarsal), graft incorporation, recurrence, secondary procedures, and complications were recorded and analyzed between graft types. RESULTS: Sixty-three feet (34 allograft and 29 xenograft) in 36 patients (mean age 9.3 y) were included. Gross Motor Function Classification System between groups was significant (P=0.001). Mean time for preoperative x-rays was 5.3 months before day of surgery (DOS) for allograft and 3.6 months for xenograft. Mean time of first and last postoperative x-ray for allograft was 3.6 and 39.5 months, respectively; for xenograft, 1.8 and 35.1 months, respectively. There was a significant difference in timing of preoperative x-ray to DOS and DOS to first postoperative x-ray (P=0.012, 0.006, respectively). Radiographically, xenograft retained postoperative improvement better than allograft, yet allograft had a higher grade 4 incorporation rate (P=0.036). The allograft group experienced significantly more cast pressure ulcers (P=0.006), but no other differences in complications between groups, and no infections were reported in either group. CONCLUSIONS: Allograft incorporated better than xenograft, likely with a greater potential to reach grade 5 incorporation, yet both groups retained postoperative improvement. Results indicate both grafts are appropriate; yet incorporation rate could affect correction maintenance, and should be considered during graft selection for Evan's procedure. LEVEL OF EVIDENCE: This study presents clinical results using a novel bone graft material. Level III-retrospective comparative study. PMID- 27379789 TI - Risk Factors for Early ACL Reconstruction Failure in Pediatric and Adolescent Patients: A Review of 561 Cases. AB - BACKGROUND: Anterior cruciate ligament (ACL) reconstruction failure is relatively common in young high-risk athletes. The purpose of this study was to examine a single center's 10-year experience with ACL reconstructions in pediatric and adolescent patients to better define short-term failure rates and risk factors for revision ACL surgery. METHODS: This institutional review board-approved retrospective study included all patients who underwent a primary ACL reconstruction between 2002 and 2013. Chart and radiographic review was performed to assess patient demographic, injury, and surgical data including growth plate status, concomitant ligament/meniscus/cartilage injury, surgical procedures, femoral drilling technique, graft source and type, femoral and tibial fixation devices, and graft size. Graft failures had to be confirmed both with clinical examination and magnetic resonance imaging or the patient had to undergo a revision ACL reconstruction. Potential factors associated with failure were evaluated using either parametric or nonparametric analysis as appropriate. RESULTS: A total of 561 ACL reconstructions were performed that met our inclusion criteria. The average patient age was 15.4 years (range, 5 to 19 y) and 53% of the patients were male. In all, 54 failures were identified for a 9.6% failure rate. Soft tissue grafts were twice as likely to fail compared with patellar tendon grafts (13% vs. 6%; P<0.001). Multivariate analysis revealed that graft choice (soft tissue vs. patellar tendon) was the primary variable predictive of failure (P<0.05), with interactions/mediating effects contributed by maturity (growth plate status) and ACL technique (P<0.05). The average time to failure was 13.6 months and hamstring grafts and anatomic femoral tunnels were both found to fail earlier (P<0.05). During the study period, approximately 8% of patients sustained a contralateral ACL injury. CONCLUSIONS: ACL failure rates in adolescent and pediatric patients vary based on patient age, graft selection, and surgical technique. Bone patellar tendon bone autografts had the lowest failure rate in this high-risk population. LEVEL OF EVIDENCE: Level IV-retrospective case series. PMID- 27379791 TI - Effective Electroconvulsive Therapy in a Patient With Psychotic Depression With Active Cushing Disease. PMID- 27379792 TI - Recurrent Right Upper Quadrant Pain Responsive Only to Electroconvulsive Therapy. PMID- 27379790 TI - Expanded Safety and Efficacy Data for a New Method of Performing Electroconvulsive Therapy: Focal Electrically Administered Seizure Therapy. AB - OBJECTIVE: Electroconvulsive therapy (ECT) is the most rapid and effective antidepressant treatment but with concerns about cognitive adverse effects. A new form of ECT, focal electrically administered seizure therapy (FEAST), was designed to increase the focality of stimulation and better match stimulus parameters with neurophysiology. We recently reported on the safety and feasibility of FEAST in a cohort (n = 17) of depressed patients. We now report on the safety, feasibility, preliminary efficacy, and cognitive effects of FEAST in a new cohort. METHODS: Open-label FEAST was administered to 20 depressed adults (6 men; 3 with bipolar disorder; age 49.1 +/- 10.6 years). Clinical and cognitive assessments were obtained at baseline and end of course. Time to orientation recovery was assessed at each treatment. Nonresponders switched to conventional ECT. RESULTS: Participants tolerated the treatment well with no dropouts. Five patients (25%) transitioned from FEAST to conventional ECT due to inadequate response. After FEAST (mean, 9.3 +/- 3.5 sessions; range, 4-14), there was a 58.1% +/- 36.0% improvement in Hamilton Rating Scale for Depression scores compared with that in the baseline (P < 0.0001); 13 (65%) of 20 patients met response criteria, and 11 (55%) of 20 met remission criteria. Patients achieved reorientation (4 of 5 items) in 4.4 +/- 3.0 minutes (median, 4.5 minutes), timed from eyes opening. There was no deterioration in neuropsychological measures. CONCLUSIONS: These findings provide further support for the safety and efficacy of FEAST. The remission and response rates were in the range found using conventional ECT, and the time to reorientation may be quicker. However, without a randomized comparison group, conclusions are tentative. PMID- 27379793 TI - Seven days of high carbohydrate ingestion does not attenuate post-exercise IL-6 and hepcidin levels. AB - PURPOSE: This investigation examined if a high carbohydrate (CHO) diet, maintained across a seven-day training period, could attenuate post-exercise interleukin-6 (IL-6) and serum hepcidin levels. METHODS: Twelve endurance-trained male athletes completed two seven-day running training blocks whilst consuming either a high (8 g kg(-1)) versus a low (3 g kg(-1)) CHO isoenergetic diet. Each training block consisted of five running sessions performed on days 1, 2, 4, 5, and 7, with the intensity and duration of each session matched between training weeks. Serum levels of Interleukin-6 (IL-6) and hepcidin were measured pre- and either immediately (IL-6) or 3-h (hepcidin) post-exercise on days 1 and 7 of each training week. RESULTS: During each training week, the immediate post-exercise IL 6 and 3-h post-exercise serum hepcidin levels were significantly elevated (both p = 0.001) from pre-exercise on days 1 and 7. These increases were not different between trials. CONCLUSIONS: These results suggest that the ingestion of a high (compared to low) CHO diet over a seven-day training period is ineffective in attenuating post-exercise IL-6 and hepcidin responses. Such results may be due to the modest training load, the increased protein intake in the low-CHO trial, and a 48 h recovery period prior to sample collection on day 7, allowing a full recovery of muscle glycogen status between exercise sessions. PMID- 27379795 TI - Understanding intercultural competence in intensive care medicine. PMID- 27379794 TI - Examining the Effects of Sodium Ions on the Binding of Antagonists to Dopamine D2 and D3 Receptors. AB - Many G protein-coupled receptors have been shown to be sensitive to the presence of sodium ions (Na+). Using radioligand competition binding assays, we have examined and compared the effects of sodium ions on the binding affinities of a number of structurally diverse ligands at human dopamine D2 and dopamine D3 receptor subtypes, which are important therapeutic targets for the treatment of psychotic disorders. At both receptors, the binding affinities of the antagonists/inverse agonists SB-277011-A, L,741,626, GR 103691 and U 99194 were higher in the presence of sodium ions compared to those measured in the presence of the organic cation, N-methyl-D-glucamine, used to control for ionic strength. Conversely, the affinities of spiperone and (+)-butaclamol were unaffected by the presence of sodium ions. Interestingly, the binding of the antagonist/inverse agonist clozapine was affected by changes in ionic strength of the buffer used rather than the presence of specific cations. Similar sensitivities to sodium ions were seen at both receptors, suggesting parallel effects of sodium ion interactions on receptor conformation. However, no clear correlation between ligand characteristics, such as subtype selectivity, and sodium ion sensitivity were observed. Therefore, the properties which determine this sensitivity remain unclear. However these findings do highlight the importance of careful consideration of assay buffer composition for in vitro assays and when comparing data from different studies, and may indicate a further level of control for ligand binding in vivo. PMID- 27379796 TI - Adverse Childhood Experiences, Support, and the Perception of Ability to Work in Adults with Disability. AB - OBJECTIVE: To examine the impact of adverse childhood experiences (ACEs) and support on self-reported work inability of adults reporting disability. PARTICIPANTS: Adults (ages 18-64) who participated in the Behavioral Risk Factor Surveillance System in 2009 or 2010 and who reported having a disability (n = 13,009). DESIGN AND MAIN OUTCOME MEASURES: The study used a retrospective cohort design with work inability as the main outcome. ACE categories included abuse (sexual, physical, emotional) and family dysfunction (domestic violence, incarceration, mental illness, substance abuse, divorce). Support included functional (perceived emotional/social support) and structural (living with another adult) support. Logistic regression was used to adjust for potential confounders (age, sex and race) and to evaluate whether there was an independent effect of ACEs on work inability after adding other important predictors (support, education, health) to the model. RESULTS: ACEs were highly prevalent with almost 75% of the sample reporting at least one ACE category and over 25% having a high ACE burden (4 or more categories). ACEs were strongly associated with functional support. Participants experiencing a high ACE burden had a higher adjusted odds ratio (OR) [95% confidence interval] of 1.9 [1.5-2.4] of work inability (reference: zero ACEs). Good functional support (adjusted OR 0.52 [0.42 0.63]) and structural support (adjusted OR 0.48 [0.41-0.56]) were protective against work inability. After adding education and health to the model, ACEs no longer appeared to have an independent effect. Structural support remained highly protective, but functional support only appeared to be protective in those with good physical health. CONCLUSIONS: ACEs are highly prevalent in working-age US adults with a disability, particularly young adults. ACEs are associated with decreased support, lower educational attainment and worse adult health. Health care providers are encouraged to screen for ACEs. Addressing the effects of ACEs on health and support, in addition to education and retraining, may increase ability to work in those with a disability. PMID- 27379797 TI - First-Year Evaluation of Mexico's Tax on Nonessential Energy-Dense Foods: An Observational Study. AB - BACKGROUND: In an effort to prevent continued increases in obesity and diabetes, in January 2014, the Mexican government implemented an 8% tax on nonessential foods with energy density >=275 kcal/100 g and a peso-per-liter tax on sugar sweetened beverages (SSBs). Limited rigorous evaluations of food taxes exist worldwide. The objective of this study was to examine changes in volume of taxed and untaxed packaged food purchases in response to these taxes in the entire sample and stratified by socioeconomic status (SES). METHODS AND FINDINGS: This study uses data on household packaged food purchases representative of the Mexican urban population from The Nielsen Company's Mexico Consumer Panel Services (CPS). We included 6,248 households that participated in the Nielsen CPS in at least 2 mo during 2012-2014; average household follow-up was 32.7 mo. We analyzed the volume of purchases of taxed and untaxed foods from January 2012 to December 2014, using a longitudinal, fixed-effects model that adjusted for preexisting trends to test whether the observed post-tax trend was significantly different from the one expected based on the pre-tax trend. We controlled for household characteristics and contextual factors like minimum salary and unemployment rate. The mean volume of purchases of taxed foods in 2014 changed by -25 g (95% confidence interval = -46, -11) per capita per month, or a 5.1% change beyond what would have been expected based on pre-tax (2012-2013) trends, with no corresponding change in purchases of untaxed foods. Low SES households purchased on average 10.2% less taxed foods than expected (-44 [-72, -16] g per capita per month); medium SES households purchased 5.8% less taxed foods than expected (-28 [-46, -11] g per capita per month), whereas high SES households' purchases did not change. The main limitations of our findings are the inability to infer causality because the taxes were implemented at the national level (lack of control group), our sample is only representative of urban areas, we only have 2 y of data prior to the tax, and, as with any consumer panel survey, we did not capture all foods purchased by the household. CONCLUSIONS: Household purchases of nonessential energy-dense foods declined in the first year after the implementation of Mexico's SSB and nonessential foods taxes. Future studies should evaluate the impact of the taxes on overall energy intake, dietary quality, and food purchase patterns (see S1 Abstract in Spanish). PMID- 27379799 TI - Column Chromatography To Obtain Organic Cation Sorption Isotherms. AB - Column chromatography was evaluated as a method to obtain organic cation sorption isotherms for environmental solids while using the peak skewness to identify the linear range of the sorption isotherm. Custom packed HPLC columns and standard batch sorption techniques were used to intercompare sorption isotherms and solid water sorption coefficients (Kd) for four organic cations (benzylamine, 2,4 dichlorobenzylamine, phenyltrimethylammonium, oxytetracycline) with two aluminosilicate clay minerals and one soil. A comparison of Freundlich isotherm parameters revealed isotherm linearity or nonlinearity was not significantly different between column chromatography and traditional batch experiments. Importantly, skewness (a metric of eluting peak symmetry) analysis of eluting peaks can establish isotherm linearity, thereby enabling a less labor intensive means to generate the extensive data sets of linear Kd values required for the development of predictive sorption models. Our findings clearly show that column chromatography can reproduce sorption measures from conventional batch experiments with the benefit of lower labor-intensity, faster analysis times, and allow for consistent sorption measures across laboratories with distinct chromatography instrumentation. PMID- 27379798 TI - Alcoholic Hepatitis Markedly Decreases the Capacity for Urea Synthesis. AB - BACKGROUND AND AIM: Data on quantitative metabolic liver functions in the life threatening disease alcoholic hepatitis are scarce. Urea synthesis is an essential metabolic liver function that plays a key regulatory role in nitrogen homeostasis. The urea synthesis capacity decreases in patients with compromised liver function, whereas it increases in patients with inflammation. Alcoholic hepatitis involves both mechanisms, but how these opposite effects are balanced remains unclear. Our aim was to investigate how alcoholic hepatitis affects the capacity for urea synthesis. We related these findings to another measure of metabolic liver function, the galactose elimination capacity (GEC), as well as to clinical disease severity. METHODS: We included 20 patients with alcoholic hepatitis and 7 healthy controls. The urea synthesis capacity was quantified by the functional hepatic nitrogen clearance (FHNC), i.e., the slope of the linear relationship between the blood alpha-amino nitrogen concentration and urea nitrogen synthesis rate during alanine infusion. The GEC was determined using blood concentration decay curves after intravenous bolus injection of galactose. Clinical disease severity was assessed by the Glasgow Alcoholic Hepatitis Score and Model for End-Stage Liver Disease (MELD) score. RESULTS: The FHNC was markedly decreased in the alcoholic hepatitis patients compared with the healthy controls (7.2+/-4.9 L/h vs. 37.4+/-6.8 L/h, P<0.01), and the largest decrease was observed in those with severe alcoholic hepatitis (4.9+/-3.6 L/h vs. 9.9+/-4.9 L/h, P<0.05). The GEC was less markedly reduced than the FHNC. A negative correlation was detected between the FHNC and MELD score (rho = -0.49, P<0.05). CONCLUSIONS: Alcoholic hepatitis markedly decreases the urea synthesis capacity. This decrease is associated with an increase in clinical disease severity. Thus, the metabolic failure in alcoholic hepatitis prevails such that the liver cannot adequately perform the metabolic up-regulation observed in other stressful states, including extrahepatic inflammation, which may contribute to the patients' poor prognosis. PMID- 27379801 TI - Increase of beta2-integrin on adhesion of THP-1 cells to collagen vitrigel membrane. AB - When human monocyte-derived leukemia (THP-1) cells, which are floating cells, are stimulated with lipid peroxides, or Streptococcus suis, these cells adhere to a plastic plate or endothelial cells. However, it is unclear whether or not non stimulated THP-1 cells adhere to collagen vitrigel membrane (CVM). In this study, firstly, we investigated the rate of adhesion of THP-1 cells to CVM. When THP-1 cells were not stimulated, the rate of adhesion to CVM was high. Then, to identify adhesion molecules involved in adhesion of THP-1 cells to CVM, expressions of various cell adhesion molecules on the surface of THP-1 cells adhering to CVM were measured. beta-actin, beta-catenin, and beta1-integrin expressions did not change in non-stimulated THP-1 cells cultured on CVM compared with those in cells cultured in a flask, but beta2-integrin expression markedly increased. PMID- 27379800 TI - Improved Clinical Risk Stratification in Patients with Long QT Syndrome? Novel Insights from Multi-Channel ECGs. AB - BACKGROUND: We investigated whether multichannel ECG-recordings are useful to risk-stratify patients with congenital long-QT syndrome (LQTS) for risk of sudden cardiac death under optimized medical treatment. METHODS: In 34 LQTS-patients (11 male; age 31+/-13 years, QTc 478+/-51ms; LQT1 n = 8, LQT2 n = 15) we performed a standard 12-channel ECG and a 120-channel body surface potential mapping. The occurrence of clinical events (CE; syncope, torsade de pointes (TdP), sudden cardiac arrest (SCA)) was documented and correlated with different ECG-parameters in all lead positions. RESULTS: Seven patients developed TdP, four survived SCA and 12 experienced syncope. 12/34 had at least one CE. CE was associated with a longer QTc-interval (519+/-43ms vs. 458+/-42ms; p = 0.001), a lower T-wave integral (TWI) on the left upper chest (-1.2+/-74.4mV*ms vs. 63.0+/-29.7mV*ms; p = 0.001), a lower range of T-wave amplitude (TWA) in the region of chest lead V8 (0.10+/-0.08mV vs. 0.18+/-0.07mV; p = 0.008) and a longer T-peak-T-end time (TpTe) in lead V1 (98+/-23ms vs. 78+/-26ms; p = 0.04). Receiver-operating characteristic (ROC) analyses revealed a sensitivity of 96% and a specificity of 75% (area under curve (AUC) 0.89+/-0.06, p = 0.001) at a cut-off value of 26.8mV*ms for prediction of CE by TWI, a sensitivity of 86% and a specificity of 83% at a cut-off value of 0.11mV (AUC 0.83+/-0.09, p = 0.002) for prediction of CE by TWA and a sensitivity of 83% and a specificity of 73% at a cut-off value of 87ms (AUC 0.80+/-0.07, p = 0.005) for prediction of CE by TpTe. CONCLUSIONS: Occurrence of CE in LQTS-patients seems to be associated with a prolonged, low amplitude T-wave. PMID- 27379803 TI - Coronary artery anomalies in children: what is the risk? AB - PURPOSE OF REVIEW: To better understand the risk of sudden death from coronary anomalies. RECENT FINDINGS: Most coronary anomalies are benign, but there are certain coronary anomalies that increase the risk of sudden cardiac death (SCD) in the young, notably anomalous aortic origin of a coronary artery from the wrong sinus. Previously, the risk of SCD attributed to certain coronary anomalies was felt to be quite high, as the risk assessment was based on autopsy series. Recent studies have shown that the risk attributed to anomalous coronary arteries is much lower than once believed. Risk appears to be highest with anomalous left coronary artery from the right sinus of Valsalva with interarterial course, notably when the young patient is participating in vigorous physical exertion, such as with competitive sports. SUMMARY: Treatment strategies may include exercise restriction or surgical repair. Management decisions should be based on a complete understanding of the risk for SCD because of anomalous coronary arteries. Future directions should focus on better methods to risk stratify these pediatric patients. PMID- 27379805 TI - Letter From the Editor: When Breath Becomes Air. PMID- 27379806 TI - Checkpoint inhibitors in breast cancer: hype or promise? PMID- 27379804 TI - ABO-incompatible heart transplantation. AB - PURPOSE OF REVIEW: ABO-incompatible (ABOi) heart transplantation (HTx) in young children has evolved from an experimental approach to a standard allocation option in many countries. Clinical and immunological research in ABOi transplantation has revealed insight into the immature immune system and its role in superior graft acceptance in childhood and antigen-specific tolerance. RECENT FINDINGS: Multicenter experience has confirmed equal actuarial survival, freedom from rejection, and graft vasculopathy comparing ABOi with ABO-compatible HTx. Observations of reduced antibody production and B-cell immunity toward the donor blood group have been confirmed in long-term follow-up. Mechanisms contributing to tolerance in this setting involve the interplay between B-cells and the complement system and the development of B-cell memory. Better characterization of the ABH polysaccharide antigens has improved diagnostic methods and clinical assessment of blood group antibodies. Boundaries regarding age, immune maturity, and therapeutic interventions to extend the applicability of ABOi HTx have been explored and resulted in data that may be useful for HTx patients beyond infancy and ABOi transplantation of other organs. Tolerance of ABH antigens possibly extends to HLA response. SUMMARY: The review provides insight into the clinical evolution of ABOi HTx and associated immunologic discoveries. Current experiences and boundaries are discussed together with recent and potential future developments for utilization in other patient and age groups. PMID- 27379802 TI - Humoral Dysregulation Associated with Increased Systemic Inflammation among Injection Heroin Users. AB - BACKGROUND: Injection drug use is a growing major public health concern. Injection drug users (IDUs) have a higher incidence of co-morbidities including HIV, Hepatitis, and other infections. An effective humoral response is critical for optimal homeostasis and protection from infection; however, the impact of injection heroin use on humoral immunity is poorly understood. We hypothesized that IDUs have altered B cell and antibody profiles. METHODS AND FINDINGS: A comprehensive systems biology-based cross-sectional assessment of 130 peripheral blood B cell flow cytometry- and plasma- based features was performed on HIV /Hepatitis C-, active heroin IDUs who participated in a syringe exchange program (n = 19) and healthy control subjects (n = 19). The IDU group had substantial polydrug use, with 89% reporting cocaine injection within the preceding month. IDUs exhibited a significant, 2-fold increase in total B cells compared to healthy subjects, which was associated with increased activated B cell subsets. Although plasma total IgG titers were similar between groups, IDUs had significantly higher IgG3 and IgG4, suggestive of chronic B cell activation. Total IgM was also increased in IDUs, as well as HIV Envelope-specific IgM, suggestive of increased HIV exposure. IDUs exhibited numerous features suggestive of systemic inflammation, including significantly increased plasma sCD40L, TNF alpha, TGF-alpha, IL-8, and ceramide metabolites. Machine learning multivariate analysis distilled a set of 10 features that classified samples based on group with absolute accuracy. CONCLUSIONS: These results demonstrate broad alterations in the steady-state humoral profile of IDUs that are associated with increased systemic inflammation. Such dysregulation may impact the ability of IDUs to generate optimal responses to vaccination and infection, or lead to increased risk for inflammation-related co-morbidities, and should be considered when developing immune-based interventions for this growing population. PMID- 27379807 TI - Personalized treatment for patients with myelofibrosis. PMID- 27379808 TI - Surveillance for hepatocellular carcinoma. PMID- 27379810 TI - What is optimal first-line treatment of unresectable or advanced BRAF-mutant melanoma? PMID- 27379811 TI - Manipulating the microbiome to improve the efficacy of immunotherapy. PMID- 27379812 TI - Clinical use of checkpoint inhibition in kidney cancer. PMID- 27379813 TI - Resistance exercise training in patients with genitourinary cancers to mitigate treatment-related skeletal muscle loss. AB - The use of targeted therapies in patients with genitourinary malignancies has significantly improved outcomes. For example, androgen receptor (AR) pathway inhibitors have improved outcomes for patients with prostate cancer, and antiangiogenic agents have improved outcomes for those with kidney cancer. However, these advances have been accompanied by musculoskeletal side effects that manifest as physical dysfunction. Although the effects of androgen deprivation therapy on skeletal muscle are well-known, an additional concern is that the muscle loss associated with these newer drugs-especially AR pathway inhibitors-may result in insulin resistance and metabolic syndrome, thus increasing the risk for cardiovascular events and diabetes. Antiangiogenic agents also may cause muscle loss, although this has been poorly described in the literature. As these targeted therapies begin to be used in the earlier stages of treatment, there will be a critical need to prevent treatment-related toxicities with nonpharmacologic interventions. Over the past decade, exercise training has emerged as a novel nonpharmacologic adjunctive method to address toxicities resulting from these targeted therapies. Despite numerous studies in patients with prostate cancer, there remains a large gap in our knowledge of the true efficacy of exercise therapy, as well as the best way to prescribe exercise programs. Here, we suggest that the central role of skeletal muscle in the development of side effects of AR pathway inhibitors and antiangiogenic agents may unlock a number of unique opportunities to study how exercise prescriptions can be used more effectively. Resistance training may be a particularly important modality. PMID- 27379814 TI - Challenges of conducting clinical trials of natural products to combat cancer. AB - Numerous drugs that the US Food and Drug Administration (FDA) has approved for use in cancer therapy are derived from plants, including taxanes such as paclitaxel and vinca alkaloids such as vinblastine. Dietary supplements are another category of natural products that are widely used by patients with cancer, but without the FDA-reviewed evidence of safety and efficacy--be it related to survival, palliation, symptom mitigation, and/or immune system enhancement-that is required for therapy approval. Nearly half of patients in the United States with cancer report that they started taking new dietary supplements after being given a diagnosis of cancer. Oncologists are challenged in providing advice to patients about which supplements are safe and effective to use to treat cancer or the side effects of cancer therapy, and which supplements are antagonistic to standard treatment with chemotherapy, radiation, and/or immunotherapy. Despite the large number of trials that have been launched, the FDA has not approved any dietary supplement or food to prevent cancer, halt its growth, or prevent its recurrence. In this article, we review the primary challenges faced by researchers attempting to conduct rigorous trials of natural products, including shortages of funding due to lack of patentability, manufacturing difficulties, contamination, and lack of product consistency. We also highlight the methods used by dietary supplement marketers to persuade patients that a supplement is effective (or at least safe) even without FDA approval, as well as the efforts of the US government to protect the health and safety of its citizens by ensuring that the information used to market natural products is accurate. We close with a summary of the most widely used databases of information about the safety, efficacy, and interactions of dietary supplements. PMID- 27379815 TI - A Two-Step Method for smFRET Data Analysis. AB - We demonstrate a two-step data analysis method to increase the accuracy of single molecule Forster Resonance Energy Transfer (smFRET) experiments. Most current smFRET studies are at a time resolution on the millisecond level. When the system also contains molecular dynamics on the millisecond level, simulations show that large errors are present (e.g., > 40%) because false state assignment becomes significant during data analysis. We introduce and confirm an additional step after normal smFRET data analysis that is able to reduce the error (e.g., < 10%). The idea is to use Monte Carlo simulation to search ideal smFRET trajectories and compare them to the experimental data. Using a mathematical model, we are able to find the matches between these two sets, and back guess the hidden rate constants in the experimental results. PMID- 27379817 TI - Gonadal agenesis with hypoplastic paramesonephric ducts (PMNDs) derivatives in dizygotic twins. AB - : The co-occurrence of gonadal agenesis alongside hypoplastic derivatives of the paramesonephric ducts has rarely been observed. PATIENT(S): 16-year-old dizygotic twin sisters were referred to our department because of primary amenorrhea. X ray, bone densitometry, ultrasonography, pelvic MRI and measurement of pituitary, ovary, and thyroid hormones were performed. Both twins showed hypergonadotropic hypogonadism, bilateral gonadal agenesis, fallopian tube, uterus, and vaginal hypoplasia but normal kidney and urinary tract structures and skeletal system. Analysis of Q-banded chromosomes in peripheral blood for the search for centromeric X-chromosome DNA and SRY gene was normal as well as the molecular analysis of FMR1, GDF9, and BMP15 genes. Estradiol gel was administered for one year followed by estroprogestin treatment. Both twins growth increased; breast development was stimulated and first menses occurred. Deregulation in the expression of the various HOX genes along the axis of the developing reproductive tract in a determinate time of development may be one of the mechanisms involved in the origin of this complex and rare association. PMID- 27379816 TI - PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis. AB - Mycobacterium tuberculosis infection presents across a spectrum in humans, from latent infection to active tuberculosis. Among those with latent tuberculosis, it is now recognized that there is also a spectrum of infection and this likely contributes to the variable risk of reactivation tuberculosis. Here, functional imaging with 18F-fluorodeoxygluose positron emission tomography and computed tomography (PET CT) of cynomolgus macaques with latent M. tuberculosis infection was used to characterize the features of reactivation after tumor necrosis factor (TNF) neutralization and determine which imaging characteristics before TNF neutralization distinguish reactivation risk. PET CT was performed on latently infected macaques (n = 26) before and during the course of TNF neutralization and a separate set of latently infected controls (n = 25). Reactivation occurred in 50% of the latently infected animals receiving TNF neutralizing antibody defined as development of at least one new granuloma in adjacent or distant locations including extrapulmonary sites. Increased lung inflammation measured by PET and the presence of extrapulmonary involvement before TNF neutralization predicted reactivation with 92% sensitivity and specificity. To define the biologic features associated with risk of reactivation, we used these PET CT parameters to identify latently infected animals at high risk for reactivation. High risk animals had higher cumulative lung bacterial burden and higher maximum lesional bacterial burdens, and more T cells producing IL-2, IL-10 and IL-17 in lung granulomas as compared to low risk macaques. In total, these data support that risk of reactivation is associated with lung inflammation and higher bacterial burden in macaques with latent Mtb infection. PMID- 27379818 TI - Placental and fetal effects of antenatal exposure to antidepressants or untreated maternal depression. AB - OBJECTIVE: To assess systematically the effects of antidepressants and untreated maternal depression on human placenta and the developing fetus. METHODS: Pertinent medical literature information was identified using MEDLINE/PubMed, SCOPUS and EMBASE. Electronic searches, limited to human studies published in English, provided 21 studies reporting primary data on placental and fetal effects of antidepressant exposure or untreated gestational depression. RESULTS: The impact of antidepressants and non-medicated maternal depression on placental functioning and fetal biochemical architecture seems to be demonstrated, although its clinical significance remains unclear. More robust data seem to indicate that exposure to either antidepressants or untreated maternal depression may induce epigenetic changes and interfere with the physiological fetal behavior. Two cases of iatrogenic fetal tachyarrhythmia have also been reported. CONCLUSIONS: Future research should clarify the clinical relevance of the impact of antidepressant and untreated maternal depression exposure on placental functioning. Moreover, ultrasound studies investigating fetal responses to antidepressants or maternal depressive symptoms are mandatory. This assessment should be performed during the whole duration of gestational period, when different fetal behavioral patterns become progressively detectable. Analyses of biochemical and epigenetic modifications associated with maternal mood symptoms and antidepressant treatment should also be implemented. PMID- 27379819 TI - Utilizing a Two-stage Design to Investigate the Safety and Potential Efficacy of Monthly Naltrexone Plus Once-daily Bupropion as a Treatment for Methamphetamine Use Disorder. AB - OBJECTIVES: This 2-stage open-label pilot study evaluated the safety and potential efficacy of naltrexone + bupropion as a pharmacotherapy for methamphetamine (MA) use disorder. METHODS: The study was conducted in 2 stages of recruitment across 3 sites; 20 participants were enrolled in stage 1 and 29 participants were enrolled in stage 2. Eight weeks of open-label pharmacotherapy with a combination of extended-release injectable naltrexone (XR-NTX; Vivitrol) plus extended-release oral bupropion (BRP; Wellbutrin XL) were provided with a smartphone-assisted medication adherence platform. Participants met Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria for severe MA use disorder, self-reported >=20 days of MA use in the 30 days prior to consent, and submitted 3 MA-positive urine drug screens (UDS) out of 4 collected during screening. Participants attended clinic twice weekly for observed BRP dosing, UDS testing, assessments, and medical management; XR-NTX was administered at weeks 1 and 5. A BRP taper and follow-up visit occurred in week 9. RESULTS: Analyses evaluated effects of XR-NTX + BRP to determine the number of "responders" according to a statistically predefined response criterion (6 of 8 MA-negative UDS during the last 4 weeks of medication). The 2-stage design required that stage 1 yield >=3 responders to continue to stage 2; 11 of the 49 participants met responder criteria across both stages (5 in stage 1, 6 in stage 2). CONCLUSIONS: Under the statistical analysis plan, study "success" required >=9 responders. With 11 responders, the study demonstrated sufficient potential of naltrexone plus bupropion as a combination pharmacotherapy for MA use disorder to warrant further study. PMID- 27379820 TI - Substance Use Disorders Among Danish Physicians: An Explorative Study of the Professional Socialization and Management of Colleagues With Substance Use Disorders. AB - AIM: This study has 2 aims. Firstly, we explore and analyze the associations between physicians' unhealthy substance use and various work-cultural and social aspects; secondly, we describe how substance use disorder (SUD defined as by Alcohol Use Disorders Identification Test [AUDIT] and Drug Use Disorders Identification Test [DUDIT]) among colleagues is managed and how physicians seek help. METHOD: During the spring of 2014, a nationwide cross-sectional study was conducted as an anonymous electronic survey among a randomly weighted sample of medical specialists, junior hospital doctors, and general practitioners in Denmark. A total of 4000 physicians (approximately 1333 from each group) were sampled, and 1943 responded (49%). The survey included the AUDIT, the DUDIT, and questions on health and psychological issues. RESULTS: Among the physicians in our study, 18.3% had an AUDIT exceeding 8 (hazardous or harmful alcohol use) and 3.2% had a DUDIT exceeding 1. Of these, 12.9% reported that their substance use had negative consequences for their social networks, and 34% to 42% reported no openness about substance use at their workplace. In total, 4 physicians (1%) of the 383 physicians with risky substance use reported to have been in regular treatment for SUDs. Most of the physicians with an unhealthy consumption of substances (78%) reported that it was irrelevant for them to seek help. Half of them reported that they had limited or insufficient knowledge of SUD. Around 55% of the physicians would encourage colleagues with SUDs to seek treatment. CONCLUSIONS: Around 50% of physicians reported that their "SUD knowledge" was relevant, but limited or not satisfactory. One-third never experienced openness about SUD at work. More than half wished to encourage a colleague with SUD to seek treatment. Three quarters of the physicians with unhealthy substance use reported that they found it irrelevant to seek help. PMID- 27379821 TI - Prognostic Significance of Percentage and Architectural Types of Contemporary Gleason Pattern 4 Prostate Cancer in Radical Prostatectomy. AB - The International Society of Urological Pathology (ISUP) 2014 consensus meeting recommended a novel grade grouping for prostate cancer that included dividing Gleason score (GS) 7 into grade groups 2 (GS 3+4) and 3 (GS 4+3). This division of GS 7, essentially determined by the percent of Gleason pattern (GP) 4 (< or >50%), raises the question of whether a more exact quantification of the percent GP 4 within GS 7 will yield additional prognostic information. Modifications were also made by ISUP regarding the definition of GP 4, now including 4 main architectural types: cribriform, glomeruloid, poorly formed, and fused glands. This study was conducted to analyze the prognostic significance of the percent GP 4 and main architectural types of GP 4 according to the 2014 ISUP grading criteria in radical prostatectomies (RPs). The cohort included 585 RP cases of GS 6 (40.2%), 3+4 (49.0%), and 4+3 (10.8%) prostate cancers. Significantly different 5-year biochemical recurrence (BCR)-free survival rates were observed among GS 6 (99%, 95% confidence interval [CI]: 97%-100%), 3+4 (81%, 95% CI: 76%-86%), and 4+3 (60%, 95% CI: 45%-71%) cancers (P<0.01). Dividing the GP 4 percent into quartiles showed a 5-year BCR-free survival of 84% (95% CI: 78%-89%) for 1% to 20%, 74% (95% CI: 62%-83%) for 21% to 50%, 66% (95% CI: 50%-78%) for 51% to 70%, and 32% (95% CI: 9%-59%) for >70% (P<0.001). Among the GP 4 architectures, cribriform was the most prevalent (43.7%), and combination of architectures with cribriform present was more frequently observed in GS 4+3 (60.3%). Glomeruloid was mostly (67.1%) seen combined with other GP 4 architectures. Unlike the other GP 4 architectures, glomeruloid as the sole GP 4 was observed only as a secondary pattern (ie, 3+4). Among patients with GS 7 cancer, the presence of cribriform architecture was associated with decreased 5-year BCR-free survival when compared with GS 7 cancers without this architecture (68% vs. 85%, P<0.01), whereas the presence of glomeruloid architecture was associated with improved 5-year BCR-free survival when compared with GS 7 cancers without this architecture (87% vs. 75%, P=0.01). However, GS 7 disease having only the glomeruloid architecture had significantly lower 5-year BCR-free survival than GS 6 cancers (86% vs. 99%, P<0.01). Multivariable Cox proportional hazards regression model for factors associated with BCR among GS 7 cancers identified age (hazard ratio [HR] 0.95, P<0.01), preoperative prostate-specific antigen (HR 1.07, P<0.01), positive surgical margin (HR 2.70, P<0.01), percent of GP 4 (21% to 50% [HR 2.21], 51% to 70% [HR 2.59], >70% [HR 6.57], all P<0.01), presence of cribriform glands (HR 1.78, P=0.02), and presence of glomeruloid glands (HR 0.43, P=0.03) as independent predictors. In conclusion, our study shows that increments in percent of GP 4 correlate with increased risk for BCR supporting the ISUP recommendation of recording the percent of GP 4 in GS 7 prostate cancers at RP. However, additional larger studies are needed to establish the optimal interval for reporting percent GP 4 in GS 7 cancers. Among the GP 4 architectures, cribriform independently predicts BCR, whereas glomeruloid reduces the risk of BCR. Distinction should be made between cribriform and glomeruloid architectures, despite glomeruloid being considered as an early stage of cribriform, as cribriform confers a higher risk for poorer outcome. PMID- 27379822 TI - Risk of thromboembolism with lymphoma: myth or reality? PMID- 27379823 TI - Adjunctive Brexpiprazole in Patients With Major Depressive Disorder and Irritability: An Exploratory Study. AB - OBJECTIVE: To evaluate the effects of adjunctive brexpiprazole on symptoms of irritability in patients with major depressive disorder (MDD). METHODS: Patients diagnosed with MDD according to DSM-IV-TR criteria who had inadequate response to antidepressant treatment continued treatment with their current antidepressant for 2 weeks. Patients still having inadequate response, and with irritability, received 6 weeks of open-label treatment with their current antidepressant at the same dose and adjunctive brexpiprazole (target dose: 3 mg/d). Brexpiprazole was discontinued at week 6, and the patients continued with their antidepressant until week 10. Changes from baseline to week 6 and week 6 to week 10 were analyzed. RESULTS: This study was conducted between October 7, 2013, and July 30, 2014. Fifty-four patients were treated with adjunctive brexpiprazole. At week 6, clinically relevant improvements were observed in Sheehan Irritability Scale total (-21.1) and item 1 (irritable mood) (-3.5) scores, Kellner Symptom Questionnaire total (-24.4) and anger-hostility subscale (-7.7) scores, and 30 item Inventory of Depressive Symptomatology, clinician version (IDS-C30), item 6 (irritable mood) score (-1.2). More (15 patients) stopped than developed (5 patients) anger attacks during treatment, as measured by the Anger Attacks Questionnaire. The Clinical Global Impressions-Severity of Illness score improved (-1.4), as did the depressive symptoms (IDS-C30 total score, -17.8; Kellner Symptom Questionnaire depression subscale score, -7.7; and Montgomery-Asberg Depression Rating Scale total score, -14.2). Irritability symptoms worsened after brexpiprazole discontinuation, assessed at week 10. Adjunctive brexpiprazole was well tolerated. CONCLUSIONS: Adjunctive treatment with brexpiprazole may represent a strategy for patients with MDD and inadequate response to antidepressant treatment who have symptoms of irritability. TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT01942785. PMID- 27379824 TI - A Subtrochanteric Femoral Stress Fracture following Bisphosphonate Treatment in an Adolescent Girl. AB - Atypical subtrochanteric and diaphyseal femoral fractures (AFFs) have emerged as a potential complication of bisphosphonate treatment in adults. Despite increasing off-label use of bisphosphonates in children and adolescents for a variety of skeletal disorders, there have been no reports of AFFs in children or adolescents outside of the osteogenesis imperfecta population. We present the case of a 16-year-old girl who developed a subtrochanteric femoral stress fracture following pamidronate treatment for idiopathic juvenile osteoporosis. PMID- 27379825 TI - Corrigendum. PMID- 27379826 TI - Influence of Left Ventricular Hypertrophy on In-Hospital Outcomes in Acute Exacerbation of Chronic Obstructive Pulmonary Disease. AB - Left ventricular hypertrophy (LVH) is associated with worse outcomes in chronic obstructive pulmonary disease (COPD); however, its role in an acute exacerbation of COPD (AECOPD) has not been reported. This was a retrospective cohort study during 2008-2012 at an academic medical center. AECOPD patients >18 years with available echocardiographic data were included. LVH was defined as LV mass index (LVMI) >95 g/m2 (women) and >115g/m2 (men). Relative wall thickness was used to classify LVH as concentric (>0.42) or eccentric (<0.42). Outcomes included need for and duration of non-invasive ventilation (NIV) and mechanical ventilation (MV), NIV failure, intensive care unit (ICU) and total length of stay (LOS), and in-hospital mortality. Two-tailed p < 0.05 was considered statistically significant. Of 802 patients with AECOPD, 615 patients with 264 (42.9%) having LVH were included. The LVH cohort had higher LVMI (141.1 +/- 39.4 g/m2 vs. 79.7 +/- 19.1 g/m2; p < 0.001) and lower LV ejection fraction (44.5+/-21.9% vs. 50.0+/ 21.6%; p <= 0.001). The LVH cohort had statistically non-significant longer ICU LOS, and higher NIV and MV use and duration. Of the 264 LVH patients, concentric LVH (198; 75.0%) was predictive of greater NIV use [82 (41.4%) vs. 16 (24.2%), p = 0.01] and duration (1.0 +/- 1.9 vs. 0.6 +/- 1.4 days, p = 0.01) compared to eccentric LVH. Concentric LVH remained independently associated with NIV use and duration. In-hospital outcomes in patients with AECOPD were comparable in patients with and without LVH. Patients with concentric LVH had higher NIV need and duration in comparison to eccentric LVH. PMID- 27379827 TI - Minimally invasive subpial tonsillectomy for Chiari I decompression. AB - BACKGROUND: A number of different surgical techniques have been used through the years to address Chiari I malformation (CMI). METHODS: This article describes how we surgically manage CMI at two high-volume centers. We call the technique the minimally invasive subpial tonsillectomy (MIST). The technique consists of a minimalistic dissection and craniectomy with a short, linear durotomy for the subpial tonsillar resection. The dura is closed without the use of a duraplasty. CONCLUSIONS: We describe our current methods of surgery for CMI. PMID- 27379828 TI - Unraveling a Patient's Post-Op Symptoms. PMID- 27379829 TI - One-carbon metabolites and telomere length in a prospective and randomized study of B- and/or D-vitamin supplementation. AB - BACKGROUND: Vitamin B deficiency is common in elderly people and has been associated with an increased risk of developing age-related diseases. B-vitamins are essential for the synthesis and stability of DNA. Telomers are the end caps of chromosomes that shorten progressively with age, and short telomers are associated with DNA instability. OBJECTIVE: In the present randomized intervention study, we investigated whether the one-carbon metabolism is related to telomere length, a surrogate marker for cellular aging. DESIGN: Sixty-five subjects (>54 years) were randomly assigned to receive either a daily combination of vitamin D3 (1200 IU), folic acid (0.5 mg), vitamin B12 (0.5 mg), vitamin B6 (50 mg) and calcium carbonate (456 mg) (group A) or vitamin D3 and calcium carbonate alone (group B). Blood testing was performed at baseline and after 1 year of supplementation. The concentrations of several metabolites of the one carbon pathway, as well as relative telomere length (RTL) and 5,10 methylenetetrahydrofolate reductase C677T genotype, were analyzed. RESULTS: At baseline, age- and gender-adjusted RTL correlated with total folate and 5 methyltetrahydrofolate (5-methylTHF). Subjects with RTL above the median had higher concentrations of total folate and 5-methylTHF compared to subjects below the median. At study end, gender- and age-adjusted RTL correlated in group A with methylmalonic acid (MMA; r = -0.460, p = 0.0012) and choline (r = 0.434, p = 0.0021) and in group B with 5,10-methenyltetrahydrofolate (r = 0.455, p = 0.026) and dimethylglycine (DMG; r = -0.386, p = 0.047). Subjects in the group A with RTL above the median had lower MMA and higher choline compared to subjects below the median. CONCLUSIONS: The present pilot study suggests a functional relationship between one-carbon metabolism and telomere length. This conclusion is supported by several correlations that were modified by B-vitamin supplementation. In agreement with our hypothesis, the availability of nucleotides and methylation groups seems to impact telomere length. Due to the small sample size and the limitations of the study, further studies should confirm the present results in a larger cohort. PMID- 27379831 TI - Silencing of epidermal growth factor, latrophilin and seven transmembrane domain containing protein 1 (ELTD1) via siRNA-induced cell death in glioblastoma. AB - The failure of therapies targeting tumor angiogenesis may be caused by anti angiogenic resistance mechanisms induced by VEGF and non-VEGF pathways alterations. Anti-angiogenic therapy failure is also attributed to immune system, acting by tumor-associated macrophages that release pro-angiogenic factors and a consequent increase of blood vessels. Recently, in a study by Rheal et al., a new angiogenic receptor, epidermal growth factor, latrophilin, and 7 trans-membrane domain-containing protein 1 on chromosome 1(ELTD1) has been identified as a promising glioma biomarker. In this study we aim to analyse whether this receptor may be used as a target molecule in glioblastoma therapy. Our results showed that small interfering RNA silencing ELTD1 caused cytotoxicity in glioblastoma cells. We also found that PDGFR, VEGFR, and their common PI3K/mTOR intracellular pathway inactivation-induced cytotoxicity in glioblastoma cells. Further, we found high percent of cytotoxicity in a low passage glioblastoma cell line after BEZ235 (a dual inhibitor of PI3K/mTOR pathway) treatment at nanomolar concentrations, compared to AG1433 (a PDGFR inhibitor) and SU1498 (a VEGFR inhibitor) that were only cytotoxic at micromolar ranges. In the future, these could prove as attractive therapeutic targets in single therapy or coupled with classic therapeutic approaches such as chemotherapy of radiotherapy. PMID- 27379830 TI - The effect of the macronutrient composition of breakfast on satiety and cognitive function in undergraduate students. AB - PURPOSE: It is believed that breakfast is an important meal due to its effect on appetite control and cognitive performance, yet little evidence exists to support this hypothesis. METHODS: Using a crossover design, 33 healthy undergraduates (aged 22 +/- 2 years with a BMI of 23.5 +/- 1.7 kg/m2) were randomized one of four breakfast treatments: no breakfast, a low-protein breakfast containing no animal protein, a high-carbohydrate/low-protein breakfast containing animal protein or a low-carbohydrate/high-protein breakfast. After an overnight fast, participants reported to the laboratory and baseline appetite questionnaires and cognitive tests were completed. A baseline blood sample was also collected. These measures were repeated at regular intervals throughout the test session. An ad libitum lunch meal was provided 240 min after breakfast, and the amount eaten recorded. Diet diaries and hourly appetite questionnaires were completed for the rest of the day. RESULTS: The no-breakfast treatment had a marked effect on appetite before lunch (p < .05). Moreover, participants consumed more energy at lunch following the no-breakfast treatment (p < .05). There was no difference in appetite before lunch or food intake at lunch following any treatment when breakfast was eaten. However, food intake over the entire test day was lowest for the no-breakfast treatment (p < .05). Plasma glucose and insulin were lower following the high-protein/low-carbohydrate treatment compared to the low protein/high-carbohydrate-no animal protein treatment (p < .05). Participants were less happy when they missed breakfast (p < .05), but there were no other statistically significant effects of breakfast on mood or cognitive performance. CONCLUSIONS: These results suggest that changing the macronutrient content of breakfast influences the glycemic response, but has no effect on the appetitive or cognitive performance measures used in this present study. PMID- 27379834 TI - Six-month Follow-up of Cervical Composite Restorations Placed With a New Universal Adhesive System: A Randomized Clinical Trial. AB - PURPOSE: The objective of this double-blind, randomized clinical trial was to evaluate the six-month clinical performance of a new universal adhesive (Xeno Select, Dentsply) in noncarious cervical lesions (NCCLs) using two evaluation criteria: World Dental Federation (FDI) and the US Public Health Service (USPHS). METHODS AND MATERIALS: A total of 124 restorations were randomly placed in 31 patients according to the following groups: ER-D = etch-and-rinse/dry dentin; ER M = etch-and-rinse/moist dentin; SE-et = selective enamel etching; and SET = self etch. The composite resin EVOLUX (Dentsply) was placed incrementally. The restorations were evaluated after one week (baseline) and at six months using the FDI and USPHS criteria. Statistical analyses were performed using appropriate tests (alpha=0.05). RESULTS: Fifteen restorations were lost or fractured at six months (one for ER-D, three for ER-M, five for SE-et, and six for SET) (p>0.05 at six-month recall). When ER (ER-D and ER-M) was compared with SE (SE-et and SET) there was a significant difference in the retention rate after six months (p=0.001). Marginal staining and postoperative sensitivity to air were only observed in three (one for ER-M and two for SET) and two restorations (two for ER D) in both evaluation criteria (p>0.05), respectively. Forty-seven restorations were considered to have minor discrepancies in marginal adaptation at the six month recall using the FDI criteria (13 for ER-D, 10 for ER-M, 11 for SE-et, and 13 for SET; p>0.05 between groups). However, for all groups, a significant difference was detected when baseline and six-month data were compared (p<0.05). CONCLUSIONS: The six-month clinical behavior of Xeno Select Universal Adhesive depends on the bonding strategy used. The universal adhesive did not fulfill the American Dental Association criteria for full approval when used in the self-etch mode. PMID- 27379833 TI - Discovery and Characterization of a Class of Pyrazole Inhibitors of Bacterial Undecaprenyl Pyrophosphate Synthase. AB - Undecaprenyl pyrophosphate synthase (UppS) is an essential enzyme in bacterial cell wall synthesis. Here we report the discovery of Staphylococcus aureus UppS inhibitors from an Encoded Library Technology screen and demonstrate binding to the hydrophobic substrate site through cocrystallography studies. The use of bacterial strains with regulated uppS expression and inhibitor resistant mutant studies confirmed that the whole cell activity was the result of UppS inhibition, validating UppS as a druggable antibacterial target. PMID- 27379832 TI - Activation Mechanism of the Bacteroides fragilis Cysteine Peptidase, Fragipain. AB - Enterotoxigenic Bacteroides fragilis produces a secreted metalloprotease known as B. fragilis toxin (BFT), which contributes to anaerobic sepsis, colitis, and colonic malignancy in mouse models of disease. A C11 family cysteine protease, fragipain (Fpn), directly activates BFT in the B. fragilis cell by removing the BFT prodomain. Fpn is itself a proenzyme and is autoactivated upon cleavage at an arginine residue in its activation loop. We have defined the proteolytic active site of Fpn, demonstrated that Fpn autoactivation can occur by an in trans loop cleavage mechanism, and characterized structural features of the Fpn activation loop that control peptidase activity against several substrates, including BFT. An arginine residue at the autocleavage site determines the fast activation kinetics of Fpn relative to the homologous C11 protease, PmC11, which is cleaved at lysine. Arginine to alanine substitution at the cleavage site ablated peptidase activity, as did partial truncation of the Fpn activation loop. However, complete truncation of the activation loop yielded an uncleaved, pro form of Fpn that was active as a peptidase against both Fpn and BFT substrates. Thus, Fpn can be transformed into an active peptidase in the absence of activation loop cleavage. This study provides insight into the mechanism of fragipain activation and, more generally, defines the role of the C11 activation loop in the control of peptidase activity and substrate specificity. PMID- 27379835 TI - Effect of Preparation Depth on the Marginal and Internal Adaptation of Computer aided Design/Computer-assisted Manufacture Endocrowns. AB - The aim of the study was to evaluate the effect of preparation depth and intraradicular extension on the marginal and internal adaptation of computer aided design/computer-assisted manufacture (CAD/CAM) endocrown restorations. Standardized preparations were made in resin endodontic tooth models (Nissin Dental), with an intracoronal preparation depth of 2 mm (group H2), with extra 1- (group H3) or 2-mm (group H4) intraradicular extensions in the root canals (n=12). Vita Enamic polymer-infiltrated ceramic-network material endocrowns were fabricated using the CEREC AC CAD/CAM system and were seated on the prepared teeth. Specimens were evaluated by microtomography. Horizontal and vertical tomographic sections were recorded and reconstructed by using the CTSkan software (TView v1.1, Skyscan).The surface/void volume (S/V) in the region of interest was calculated. Marginal gap (MG), absolute marginal discrepancy (MD), and internal marginal gap were measured at various measuring locations and calculated in microscale (MUm). Marginal and internal discrepancy data (MUm) were analyzed with nonparametric Kruskal-Wallis analysis of variance by ranks with Dunn's post hoc, whereas S/V data were analyzed by one-way analysis of variance and Bonferroni multiple comparisons (alpha=0.05). Significant differences were found in MG, MD, and internal gap width values between the groups, with H2 showing the lowest values from all groups. S/V calculations presented significant differences between H2 and the other two groups (H3 and H4) tested, with H2 again showing the lowest values. Increasing the intraradicular extension of endocrown restorations increased the marginal and internal gap of endocrown restorations. PMID- 27379836 TI - Effect of Storage Time on Bond Strength Performance of Multimode Adhesives to Indirect Resin Composite and Lithium Disilicate Glass Ceramic. AB - PURPOSE: To investigate the bond strength performance of multimode adhesives (MMAs) to indirect resin composite and lithium disilicate glass ceramic after 24 hours or one year of water storage. METHODS AND MATERIALS: Thirty flat and polished plates of indirect resin composite (Epricord) and thirty lithium disilicate glass ceramic plates (IPS e.max Press) were prepared. Surfaces were pretreated using sandblasting (indirect resin composite) or hydrofluoric acid (glass-based ceramic). Specimens were bonded with one of two MMAs (Scotchbond Universal [SBU] or All-Bond Universal [ABU]) or ceramic primer and hydrophobic bonding (RelyX Ceramic Primer and Adper Scotchbond Multi-Purpose Bond) as a control (n=10). Resin cement cylinders (0.75 mm in diameter * 0.5 mm in height) were bonded to both substrate surfaces using the respective adhesives. After 24 hours or one year of water storage, bonding performance was measured by microshear bond strength (MSBS) testing. Results were analyzed using three-way ANOVA with Bonferroni post hoc tests (alpha=0.05). RESULTS: For indirect resin composite, significantly higher MSBS values were found for ABU after 24 hours (ABU > SBU = control); however, no significant difference among the adhesives was observed after one year (p>0.05). For glass-based ceramic, significantly different bond strengths were observed among the adhesives after 24 hours (control = ABU > SBU) and one year (control > SBU = ABU; p<0.05). CONCLUSIONS: Both MMAs tested can be considered effective alternatives for bonding to sandblasted indirect resin composite after aging, as they showed similar bond performance to that of the control group. However, separate bottles of silane bonding resin showed higher MSBS values and more durable bonding for etched glass based ceramic. PMID- 27379838 TI - MicroRNA-205-5p is upregulated in myelodysplastic syndromes and induces cell proliferation via PTEN suppression. AB - Micro (mi)RNA dysregulation is implicated in the development of myelodysplastic syndrome (MDS). Chromosomal abnormalities on 1q are frequently detected in Korean patients with MDS; however, how these are related to disease development is unknown. The present study compared the expression profiles of miRNAs encoded by chromosome 1q between 65 MDS patients and 11 controls. We found that miR-205-5p levels were 12.5 fold higher in the former (P=0.001). miR-205-5p level was increased in 44.7% of patients when an arbitrary 2(-DeltaCt) cut-off value of 1.25 was used. miR-205-5p expression data were used to generate a receiver operating characteristic (ROC) curve for miR-205-5p, for which the area under the curve (AUC) was 0.825 (95% confidence interval: 0.710-0.941; P=0.001). Moreover, transfection with a miR-205-5p mimic induced cell proliferation by inhibiting the expression of the tumor suppressor protein phosphatase and tensin homolog (PTEN). Our findings suggest that miR-205-5p upregulation contributes to MDS by suppressing PTEN and that miR-205-5p thus acts as an oncogene in hematopoietic cells. PMID- 27379839 TI - White Light Emission in Butadiyne Bridged Pyrene-Phenyl Hybrid Fluorophore: Understanding the Photophysical Importance of Diyne Spacer and Utilizing the Excited-State Photophysics for Vapor Detection. AB - Generation of white light emission (WLE) from a single organic fluorophore is challenging because of the need to get fluorescence covering the visible region (400-700 nm) upon excitation of the dye at near-ultraviolet wavelength. Herein, we report WLE from a butadiyne bridged pyrene-phenyl hybrid fluorophore in mixed aqueous solvents as well as in polymer film matrices. The ability of the butadiynyl dye to emit from multiple excited states such as locally excited (LE; 400-500 nm), aggregate (excimer type; 475-600 nm), and charge transfer (CT; 500 750 nm) states spanning the emission almost throughout the visible range has made the generation of the white light to be possible. In highly polar solvent such as acetonitrile, the butadiynyl dye emits from the LE and CT states, and the WLE is achieved through a control of the dye concentration such that intermolecular CT (exciplex type) contributes along with the intramolecular CT and LE emissions. In mixed-aqueous systems such as water-acetonitrile and water-N,N-dimethylformamide, the CT emission is red-shifted (because of the high dielctric constant of water), and the contribution of the aggregate emission (originated because of the poor solvent water) is important in maintaining the relative distribution of the fluorescence intensities (LE, excimer, and CT) in the entire visible region. The significance of the diyne spacer in achieving the WLE is delineated through a control study with a single acetylenic analogue. The LE, aggregate, and CT emissions are involved in generating bluish-white light in a poly(vinyl alcohol) film matrix of the butadiynyl dye. Blue emission is noted in a poly(methyl methacrylate) (PMMA) film matrix of the dye with a major contribution from the LE and a minor contribution from the aggregate state. Exposure of the PMMA film of the dye to polar aprotic vapors assists in gaining the CT state emission such that the LE, aggregate, CT emissions cover the entire visible region to produce the WLE. This opens a new strategy for selective vapor sensing. PMID- 27379837 TI - Traumatic brain injury decreases AMP-activated protein kinase activity and pharmacological enhancement of its activity improves cognitive outcome. AB - Prolonged metabolic suppression in the brain is a well-characterized secondary pathology of both experimental and clinical traumatic brain injury (TBI). AMP activated kinase (AMPK) acts as a cellular energy sensor that, when activated, regulates various metabolic and catabolic pathways to decrease ATP consumption and increase ATP synthesis. As energy availability after TBI is suppressed, we questioned if increasing AMPK activity after TBI would improve cognitive outcome. TBI was delivered using the electromagnetic controlled cortical impact model on male Sprague-Dawley rats (275-300 g) and C57BL/6 mice (20-25 g). AMPK activity within the injured parietal cortex and ipsilateral hippocampus was inferred by western blots using phospho-specific antibodies. The consequences of acute manipulation of AMPK signaling on cognitive function were assessed using the Morris water maze task. We found that AMPK activity is decreased as a result of injury, as indicated by reduced AMPK phosphorylation and corresponding changes in the phosphorylation of its downstream targets: ribosomal protein S6 and Akt Substrate of 160 kDa (AS160). Increasing AMPK activity after injury using the drugs 5-amino-1-beta-d-ribofuranosyl-imidazole-4-carboxamide or metformin did not affect spatial learning, but significantly improved spatial memory. Taken together, our results suggest that decreased AMPK activity after TBI may contribute to the cellular energy crisis in the injured brain, and that AMPK activators may have therapeutic utility. Increased phosphorylation of Thr172 activates AMP-activated protein kinase (AMPK) under conditions of low cellular energy availability. This leads to inhibition of energy consuming, while activating energy generating, processes. Hill et al., present data to indicate that TBI decreases Thr172 phosphorylation and that its stimulation by pharmacological agents offers neuroprotection and improves memory. These results suggest that decreased AMPK phosphorylation after TBI incorrectly signals the injured brain that excess energy is available, thereby contributing to the cellular energy crisis and memory impairments. PMID- 27379840 TI - Dead Sea ultraviolet climatotherapy for children with atopic dermatitis. AB - BACKGROUND: Atopic dermatitis (AD) is a common, chronic, and relapsing inflammatory skin disorder. Moderate to severe cases represent an extremely disabling disease, for both children and their parents. Dead Sea climatotherapy (DSC), recognized as a natural treatment for patients with skin diseases, takes advantage of the selectively scattered ultraviolet irradiation (UV) present at the lowest terrestrial site on the earth. OBJECTIVES: To investigate the impact on short-term results of DSC in moderate to severe AD children from the Czech Republic treated 4 weeks at the Deutsches Medizinisches Zentrum (DMZ), Israel, and to correlate their results to the cumulative UVA and UVB irradiation doses received during treatment. PATIENTS AND METHODS: Seventy-two patients aged <19 years were divided into three groups and treated in March 2014, October 2014, and March 2015 with gradually increasing sun exposure during 28 consecutive days. Daily and cumulative exposure doses of UVB and UVA were calculated through patients' recorded sun exposure logs. The SCORing Atopic Dermatitis (SCORAD) index was recorded immediately after DSC and 3 months later by the same dermatologist. RESULTS: Good clinical results were observed in all groups, with overall improvement in SCORAD reaching 87.5 +/- 13.4% and 71.3 +/- 21.3% immediately after DSC and 3 months later, respectively. No side effects were observed during the treatments. Higher cumulative exposure times correlated with better results and enhanced remission. CONCLUSION: Dead Sea climatotherapy represents a valuable option for the treatment of AD in children. Medically controlled and prescribed sun exposure seems to directly and positively influence the results obtained. PMID- 27379841 TI - Insertion of intra-oral electrodes for cranial nerve monitoring using a Crowe Davis retractor. AB - Acoustic neuroma resection is an example of a neurosurgical procedure where the brainstem and multiple cranial nerves are at risk for injury. Electrode placement for monitoring of the glossopharyngeal and hypoglossal nerves during acoustic neuroma resection can be challenging. The purpose of this report is to illustrate the use of a device for intra-oral electrode placement for intraoperative monitoring of the glossopharyngeal and hypoglossal nerves. A 60-year-old male presented for acoustic neuroma resection. Under general anesthesia, a Crowe-Davis retractor was used to open the mouth, providing access to the posterior pharynx. For glossopharyngeal monitoring, two bent subdermal needle electrodes were inserted just lateral to the uvula. Two additional electrodes were inserted on the lateral tongue to monitor the hypoglossal nerve. Cranial nerves monitoring was conducted utilizing both free running and triggered electromyography of the trigeminal and facial nerves in addition to the lower cranial nerves. The tumor was resected successfully. Monitoring of the cranial nerves (including the glossopharyngeal and hypoglossal nerves) revealed no concerning responses. The Crowe-Davis retractor and the technique described allowed insertion of electrodes for neural monitoring, contributing to neural preservation. PMID- 27379842 TI - Genetic and molecular characterization of a novel reassortant H2N8 subtype avian influenza virus isolated from a domestic duck in Zhejiang Province in China. AB - The circulation of the H2 subtype influenza viruses in domestic animals increases the risk of human exposure to these viruses. An H2N8 avian influenza virus (AIV) was isolated from a domestic duck during AIV surveillance of poultry in live poultry markets (LPMs) in Zhejiang Province, Eastern China, in 2013. The phylogenetic trees suggested that this strain is a novel reassortant virus derived from multiple AIV subtypes from aquatic birds and poultry in Eastern Asia. Although this reassortant strain exhibited low pathogenicity in mice, it was able to replicate in the lungs of the mice without prior adaptation. Continued surveillance of domestic ducks in LPMs is required for early detection of AIV outbreaks in poultry and humans. PMID- 27379843 TI - Phenotypic variability in two infants sharing the same MECP2 mutation: evidence of chromosomal rearrangements and high sister-chromatid exchange levels in Rett syndrome. AB - Rett syndrome (RTT) whose major cause is the mutations in the X-linked MECP2 gene is a genetic disease that affects females. We screened two RTT patients using cytogenetic studies and in silico analysis as well as molecular analysis by the direct sequencing of MECP2. The cytogenetic results showed that although patient A was karyotypically normal, patient B showed chromosomal abnormalities, including chromosomal breakage in both chromosomes 2 and 5. In addition, chromosome 9 was detected on heteromorphic pattern (9ph+). A significant increase in sister-chromatid exchange (SCE) frequency was also observed in this patient. Although both patients were karyotypically different, they share the same MeCP2 mutation (p.P152R) which was predicted to be deleterious. To our knowledge, we describe the first association between MECP2 mutation, chromosomal abnormalities and high SCE frequency, which further validates the importance of the thorough chromosomal and molecular analyses that should be performed on the suspected RTT cases. PMID- 27379844 TI - Investigation of contactless detection using a giant magnetoresistance sensor for detecting prostate specific antigen. AB - This paper presents a contactless detection method for detecting prostate specific antigen with a giant magnetoresistance sensor. In contactless detection case, the prostate specific antigen sample preparation was separated from the sensor that prevented the sensor from being immersed in chemical solvents, and made the sensor implementing in immediately reuse without wash. Experimental results showed that applied an external magnetic field in a range of 50 Oe to 90 Oe, Dynabeads with a concentration as low as 0.1 MUg/mL can be detected by this system and could give an approximate quantitation to the logarithmic of Dynabeads concentration. Sandwich immunoassay was employed for preparing PSA samples. The PSA capture was implemented on a gold film modified with a self-assembled monolayer and using biotinylated secondary antibody against PSA and streptavidinylated Dynabeads. With DC magnetic field in the range of 50 to 90 Oe, PSA can be detected with a detection limit as low as 0.1 ng/mL. Samples spiked with different concentrations of PSA can be distinguished clearly. Due to the contactless detection method, the detection system exhibited advantages such as convenient manipulation, reusable, inexpensive, small weight. So, this detection method was a promising candidate in biomarker detection, especially in point of care detection. PMID- 27379845 TI - Improved synthesis and growth of graphene oxide for field effect transistor biosensors. AB - Reduced graphene oxide (RGO) has many advantages over graphene such as low-cost, aqueous processable and industrial-scalable. However, two main limitations that prevent the use of RGO in electronics are the high electrical resistance and large electrical resistance deviation between fabricated devices. This limits RGO's use in biosensors, capacitors and other electronic devices. Herein, we present (1) a modified Hummer's method to obtain large RGO flakes via in-situ size fractionation and (2) the novel growth of RGO which can bridge the gaps in between existing RGO flakes. Together, these two processes reduced the electrical resistance drastically from 1.99E + 06 to 4.68E + 03 Omega/square and the standard deviation decreased from 80.5 % to 16.5 %. The RGO was then fabricated into a field-effect transistor biosensor. A 1 pmol to 100 nmol change in Cytochrome C protein corresponded to a 3 % change in electrical resistance. The reported improved RGO synthesis method and subsequent growth enable large-scale application of RGO in practical electronic devices such as biosensors. PMID- 27379846 TI - Androgenesis, gynogenesis, and parthenogenesis haploids in cucurbit species. AB - Haploids and doubled haploids are critical components of plant breeding. This review is focused on studies on haploids and double haploids inducted in cucurbits through in vitro pollination with irradiated pollen, unfertilized ovule/ovary culture, and anther/microspore culture during the last 30 years, as well as comprehensive analysis of the main factors of each process and comparison between chromosome doubling and ploidy identification methods, with special focus on the application of double haploids in plant breeding and genetics. This review identifies existing problems affecting the efficiency of androgenesis, gynogenesis, and parthenogenesis in cucurbit species. Donor plant genotypes and surrounding environments, developmental stages of explants, culture media, stress factors, and chromosome doubling and ploidy identification are compared at length and discussed as methodologies and protocols for androgenesis, gynogenesis, and parthenogenesis in haploid and double haploid production technologies. PMID- 27379847 TI - [Not Available]. PMID- 27379848 TI - A new synthesis of S-aryl uracils from aryl thiols and 6-amino uracils in the presence of NCS. AB - Sulfenylchloride intermediates generated from the reaction of aryl thiols with N chlorosuccinimide were trapped by 6-amino uracil derivatives to yield 6-amino-5 (arylthio)-pyrimidine-2,4(1H,3H)-dione compounds at room temperature. PMID- 27379849 TI - Palmar hyperhidrosis treated by noninvasive ultrasound stellate ganglion block. AB - Focal palmar hyperhidrosis is a common and often debilitating eccrine sweat gland disorder with negative impact on quality of life and self-esteem. For treatment of recalcitrant cases, a stellate ganglion block is a nonsurgical alternative. Although this method has only a temporary effect, surgical risks can be avoided. The usual way to perform the block is by ultrasound-guided injection of local anesthetics. Here we describe the use of therapeutic ultrasound at 0.8 MHz for stellate ganglion block. Ultrasound was applied for 1 min unilaterally every other day for 6 days. The efficacy was monitored by video capillaroscopy and Minor's iodine starch test. Treatment was well tolerated and no adverse effects were noted. Sweating was stopped and capillary blood flow increased. The effect lasted for several weeks. PMID- 27379850 TI - Cutaneous Langerhans cell histiocytosis : The spectrum of a rare cutaneous neoplasia. AB - Langerhans cell histiocytosis (LCH) is a rare disorder that is now recognized as a true malignancy of dendritic Langerhans cells. Various somatic mutations have been discovered for BRAF and MAP kinases. The clinical variability is remarkable. A very rare variant is cutaneous LCH without internal organ manifestations. We present a case series of cutaneous LCH illustrating the spectrum of clinical symptoms, treatment, and disease course. Cutaneous LCH needs a careful investigation of possible internal involvement and a long follow-up since second malignancies may develop over time. Overtreatment should be avoided, since too aggressive treatment will not improve the outcome. PMID- 27379851 TI - [Differential diagnosis of skin changes on the lower extremities in chronic venous insufficiency]. AB - Varicous veins and postthrombotic syndrome can make typical reversible or irreversible skin changes on the lower extremities if no treatment is initiated. The typical clinical signs should be recognised in an early stage and possible differential diagnoses have to be excluded. PMID- 27379852 TI - [Cardiac herniation and torsion after transpericardial pneumonectomy]. AB - This article presents the case of a 43 year old woman with right-sided lung cancer. She underwent transpericardial pneumonectomy. After an uneventfull surgery, the patient was transferred to the intensive care unit for postoperative monitoring. She was hemodynamically stable and had already been extubated in the OR.On postoperative chest X-ray a mediastinal shift to the operated side as well as a herniation of the heart into the right chest cavity was detected. While the patient remained hemodynamically stable a computed tomography of the chest was performed which confirmed the diagnosis of cardiac herniation and torsion. The lady underwent rethoracotomy the following day where the heart was repositioned and the pericardial defect was closed. She made an uneventfull recovery.Five years after the pneumonectomy she remains well and is without relapse of lung cancer.Mechanism for cardiac herniation and torsion, the clinical presentation and the typical radiologic signs are discussed. However, the clue to early diagnosis is a high index of clinical suspicion.It is highlighted that a hemodynamically unstable patient under these circumstances demands urgent rethoracotomy. PMID- 27379853 TI - [Practical Aspects of Sclerotherapy]. AB - Sclerotherapy is an important part of the treatment of varicose veins. It may also be performed in patients with contraindications for operative procedures. By adjusting the mode of application (liquid or foam) and the concentration it can be used for the treatment of all vein types. In comparison to other treatment options it is especially well suited for the treatment of spider veins and reticular veins, pudendal varicosity and so called "feeding" varicose veins in the proximity of venous leg ulcers. A current European guideline, which was approved by 23 European phlebologic societies, supports the good international standardization of this treatment technique. PMID- 27379854 TI - Pyoderma gangrenosum-a novel approach? AB - Pyoderma gangrenosum (PG) represents a rare skin disorder, with several clinical variants and still not fully understood ethiopathogenesis. Often associated with inflammatory or neoplastic disease, PG is nowadays considered an inflammatory neutrophilic disease with common underlying morbidity. Modern treatment options are oriented towards key mechanisms underlying the pathogenesis of the disease, namely inflammatory mediators, and seem to be the most effective treatment currently available. Although promising, the results are not invariable and these treatments are sometimes surrounded by controversy, as recent studies have reported cases that are refractory to therapy with biological agents. It is possible that refractoriness to the use of biological agents as monotherapy stems from the fact that a single agent is not able to affect the entire inflammatory cascade, or to simultaneously influence all of its levels. Based on the pathogenesis of inflammation, we can suggest that an ideal targeted therapy should be able to induce the following changes: 1) reduction of the secretion of interleukin (IL)-1a/b from the inflammasome with subsequent blocking of its biological effect (by therapy with IL-1 receptor antagonists); 2) blocking of the activation of the secreted procytokines in their active form (by therapy with caspase-1 inhibitors; 3) blocking of the effect of the already released active cytokines (by therapy with tumour necrosis factor alpha, TNF-alpha, inhibitors); 4) blocking of the effector action of the cytokines on the target intracellular molecules (by therapy with kinase inhibitors). The specific therapy should aim to attack more than one link in the inflammatory cascade, in order to achieve maximum therapeutic effectiveness. Most surely, this could be achieved with combined therapy with different groups of biological agents (for example a combined therapy with IL-1 receptor antagonist and a TNF-alpha inhibitor). Currently, no data in the literature exist to support this statement, and there are no safety data relating to such approaches. We focus this review on the novel etiopathogenetic concepts of PG and the future therapeutic approaches based on blocking different levels of the inflammatory cascade, which seems to be the most promising weapon in the target-oriented treatment options. PMID- 27379855 TI - [Drug Treatment of Chronic Venous Diesease]. AB - Chronic venous disease (CVD) affects at least 15-25 % of the general population incurring not only high morbidity but also considerable economical burden. The mainstay of modern treatment of CVD are endovenous therapeutic procedures and compression therapy. As far as the pathogenesis of CVD is being gradually unraveled the interest in drugs able to impact the process is growing. Here we have presented an overview of a majority of oral preparations used so far to treat CVD including venous leg ulcers. After several decades of clinical use a few flavonoid preparations, in the first place micronized purified flavonoid fraction, collected enough evidence to recommend them as a short-term adjunct treatment of CVD. However, other compounds are also promising in this regards. Yet, we need more larger and longer-term clinical trials to more precisely define effects, cost-effectiveness and, above all, capacity for prophylactic application of the drugs. Learning more about basis of CVD will help design new drugs directed at specific aspects of the disease process. PMID- 27379857 TI - [Hallux amputation]. AB - OBJECTIVE: Debridement of infected tissue with the main aim being the re establishment of mobilization with preservation of standing and walking ability. Prevention of secondary pressure points or amputations due to inadequate resection or deficient soft tissue cover. INDICATIONS: In the case of increasing necrosis of the big toe, surgical abrasion and/or amputation is considered unavoidable. Other indications where surgery could be considered include diabetes and its associated angiopathies together with peripheral arterial angiopathy. CONTRAINDICATIONS: In the case of insufficient blood supply an expansion of the resection margins should be taken into account. If there are possible alternatives to amputation. Surgery for patients with renal failure requiring dialysis associated with increased complication rate. SURGICAL TECHNIQUE: A dorsal cuneiform resection is performed to facilitate implantation of a plantar skin transplant and wound healing. Important is the resection of bone in a slide oblique technique. Amputation scars should be outside pressure zones. Partial amputations in the area of the first ray as exarticulation or via the individual amputated segments possible (as opposed to toes 2-5). POSTOPERATIVE MANAGEMENT: Direct postoperative weight-bearing with rigid insole and dispensing aid for 6-8 weeks. Following complete wound healing, foot support with orthopedic arch and transverse strain relief should be advocated, together with a joint roll in ready made individual shoes. RESULTS: Both trauma and nontrauma cases were included in our present cohort. A total of 7 cases were surgically revised in 2014 due to superficial skin necrosis that was likely the result of skin tension from the wound stitches. PMID- 27379856 TI - [Arthroscopic refixation of TFCC by bone screw anchor]. AB - OBJECTIVE: The goal of this operation technique is a stable refixation of the triangular fibrocartilage complex (TFCC) to the fovea ulnaris. The stability of the distal radio-ulnar joint (DRUJ) should be re-established. The patients pain and the feeling of instability should be reduced. INDICATIONS: Lesions of the foveal component of the TFCC resulting in DRUJ instability. Combined lesions of both components of the TFCC. Complete detachment of the TFCC from the ulna either without fracture of the styloid process of the ulna or with fracture (floating styloid). CONTRAINDICATIONS: Severe lacerations of the TFCC and clinically relevant arthrosis of the DRUJ. Severely osteoporotic bone. SURGICAL TECHNIQUE: Following diagnostic arthroscopy and performance of stability control of the TFCC with a palpation hook, reduction of the DRUJ with supination position of the wrist. Bone anchor fixation through the direct foveal portal (DF). Under arthroscopic control through the 3/4 portal, the suture from the DF portal is placed through the TFCC. Pull out and tie the strands through the 6 U portal. POSTOPERATIVE MANAGEMENT: Restriction of rotation of the forearm in a Munster cast or special cast brace for 6 weeks. Self-controlled exercise of the wrist after 6 weeks. Physiotherapy and strength building 8 weeks postoperatively. RESULTS: Clinical studies of this technique showed a significant amelioration of pain perception, improved range of motion and DASH score in all patients after anchor fixation. The results are comparable to other techniques. All patients returned to work after the operation. Accordingly, using this technique a very good stabilization of the DRUJ with low complications can be achieved. PMID- 27379859 TI - Optical Characterization of Commercial Lithiated Graphite Battery Electrodes and in Situ Fiber Optic Evanescent Wave Spectroscopy. AB - Optical characterization of graphite anodes in lithium ion batteries (LIB) is presented here for potential use in estimating their state of charge (SOC). The characterization is based on reflectance spectroscopy of the anode of commercial LIB cells and in situ optical measurements using an embedded optical fiber sensor. The optical characterization of the anode using wavelengths ranging from 500 to 900 nm supports the dominance of graphite over the solid electrolyte interface in governing the anode's reflectance properties. It is demonstrated that lithiated graphite's reflectance has a significant change in the near infrared band, 750-900 nm, compared with the visible spectrum as a function of SOC. An embedded optical sensor is used to measure the transmittance of graphite anode in the near-infrared band, and the results suggest that a unique inexpensive method may be developed to estimate the SOC of a LIB. PMID- 27379858 TI - [Arthroscopic partial resection of the ulnar head for ulnocarpal decompression]. AB - OBJECTIVE: Arthroscopic decompression (wafer procedure) of the ulnocarpal compartment in patients with ulnar impaction syndrome. INDICATIONS: The arthroscopic wafer procedure is recommended in ulnar-plus situations with up to 3 mm length-excess. To perform this procedure the ulnar head needs to be accessible for the burr through a pre-existing, impaction-related, centroradial lesion of the triangular fibrocartilage complex (TFCC). The additional presence of a distal radioulnar joint (DRUJ) type C confirms the indication. CONTRAINDICATIONS: The wafer procedure is contraindicated if there is no consistent TFCC injury ensuring access to the ulnar head and furthermore in ulna-plus situations of more than 3 mm. Relative contraindications: in young patients due to lack of evidence-based studies. SURGICAL TECHNIQUE: Arthroscopic, semicircular, partial resection of the ulnar head in terms of oblique-helicoidal osteotomy using a 4.2 mm burr, while sparing the DRUJ and the dorsal and the palmar radioulnar ligaments. POSTOPERATIVE MANAGEMENT: Immobilization for 1 week in a palmar splint with immediate intensive exercising of pro- and supination under physiotherapeutic instruction. RESULTS: Between 2008 and 2010, an arthroscopic wafer procedure was performed in 24 patients. The resection of the ulnar head was 2.5 mm on average. After a mean follow-up time of 13.25 months, very good results were archived in 23 of 24 patients; the ulnar impingement test was negative. On a visual analog scale (0-10) average postoperative pain was 1.16 at rest and 4.5 under stress. The mean postoperative DASH score was 13.4. PMID- 27379861 TI - Common and Rare Ocular Side-effects of the Dexamethasone Implant. AB - PURPOSE: Expanding indications for use, and overall increased use of the slow release dexamethasone (DEX) implant yields an opportunity to study the reported ocular side-effects and adverse events associated with this drug. METHODS: A PubMed.gov (US National Library of Medicine, National Institutes of Health) review of literature for the search terms, "Ozurdex and complication," through December 2015. RESULTS: Ocular hypertension and cataract are the main long-term sequelae identified in large, randomized clinical trials. Case reports have emerged regarding implant migration, complications with implantation, infection, and posterior segment sequelae, including vitreomacular traction. CONCLUSION: DEX implant overall is well-tolerated and, with careful monitoring, can be a useful adjunct to treating macular edema associated with diabetes, retinal vein occlusion, and chronic uveitis. PMID- 27379862 TI - Students in Telemedicine: A Lasting Impact. PMID- 27379863 TI - Introduction to a Special Issue on IFN Regulatory Factors in Innate Immune Responses. PMID- 27379864 TI - IFN Regulatory Factors and Antiviral Innate Immunity: How Viruses Can Get Better. AB - The interferon regulatory factor (IRF) family consists of transcriptional regulators that exert multifaceted and versatile functions in multiple biological processes. Their crucial role as central mediators in the establishment and execution of host immunity in response to pathogen-derived signals downstream pattern recognition receptors (PRRs) makes IRFs a hallmark of the host antiviral response. They function as hub molecules at the crossroad of different signaling pathways for the induction of interferon (IFN) and inflammatory cytokines, as well as of antiviral and immunomodulatory genes even in an IFN-independent manner. By regulating the development and activity of immune cells, IRFs also function as a bridge between innate and adaptive responses. As such, IRFs represent attractive and compulsive targets in viral strategies to subvert antiviral signaling. In this study, we discuss current knowledge on the wide array of strategies put in place by pathogenic viruses to evade, subvert, and/or hijack these essential components of host antiviral immunity. PMID- 27379865 TI - Transcriptional and Epigenetic Regulation of Innate Immune Cell Development by the Transcription Factor, Interferon Regulatory Factor-8. AB - The transcription factor, interferon regulatory factor-8 (IRF8), is required for the development of monocytes, macrophages, dendritic cells (DCs), basophils, and eosinophils, while it inhibits the generation of neutrophils. Recently, the molecular mechanisms by which IRF8 regulates their development have been increasingly clarified by genome-wide analyses, including chromatin immunoprecipitation-sequencing and transcriptome profiling. IRF8 associates with the myeloid master transcription factor, PU.1, to promote the establishment of cell-type-specific enhancers and gene expression, thereby driving monocyte development or maintaining the plasmacytoid DC-specific gene expression profiles. Furthermore, microbial stimulation enables IRF8 to associate with other transcription factors, including IRF1, to induce immune response genes. Knowledge about the regulation of Irf8 expression in myeloid development has also increased. In this review, we discuss recent advances in our understanding of transcriptional and epigenetic regulation involving IRF8 in the development of myeloid cells. PMID- 27379868 TI - Specificity and Function of IRF Family Transcription Factors: Insights from Genomics. AB - The effective deployment of immune responses depends on the activation of well defined signaling pathways that interact with cell-intrinsic epigenetic features to control the activation of stimulus-specific and kinetically accurate gene expression programs. The interferon regulatory factors (IRFs) are critical regulators of both development and activation of distinct cells of the immune system. The influence of the IRF family transcription factors (TFs) on immune responses is mainly linked to the control of the type I interferon (IFN) system, which must be not only rapidly activated to mount an efficient host response, but also tightly regulated to avoid detrimental effects. In this review we discuss the different regulatory layers controlling IRF activity and specifically IRF mediated IFN responses. We also highlight how the interplay between the DNA binding properties of the IRF family TFs and the epigenetic landscape controls cell- and context-specific responses. PMID- 27379866 TI - Relevance of Interferon Regulatory Factor-8 Expression in Myeloid-Tumor Interactions. AB - Perturbations in myelopoiesis are a common feature in solid tumor biology, reflecting the central premise that cancer is not only a localized affliction but also a systemic disease. Because the myeloid compartment is essential for the induction of adaptive immunity, these alterations in myeloid development contribute to the failure of the host to effectively manage tumor progression. These "dysfunctional" myeloid cells have been coined myeloid-derived suppressor cells (MDSCs). Interestingly, such cells not only arise in neoplasia but also are associated with many other inflammatory or pathologic conditions. MDSCs affect disease outcome through multiple mechanisms, including their ability to mediate generalized or antigen-specific immune suppression. Consequently, MDSCs pose a significant barrier to effective immunotherapy in multiple disease settings. Although much interest has been devoted to unraveling mechanisms by which MDSCs mediate immune suppression, a large gap has remained in our understanding of the mechanisms that drive their development in the first place. Investigations into this question have identified an unrecognized role of interferon regulatory factor-8 (IRF-8), a member of the IRF family of transcription factors, in tumor induced myeloid dysfunction. Ordinarily, IRF-8 is involved in diverse stages of myelopoiesis, namely differentiation and lineage commitment toward monocytes, dendritic cells, and granulocytes. Several recent studies now support the hypothesis that IRF-8 functions as a "master" negative regulator of MDSC formation in vivo. This review focuses on IRF-8 as a potential target suppressed by tumors to cripple normal myelopoiesis, redirecting myeloid differentiation toward the emergence of MDSCs. Understanding the bases by which neoplasia drives MDSC accumulation has the potential to improve the efficacy of therapies that require a competent myeloid compartment. PMID- 27379867 TI - Epigenetic Mechanisms Governing Innate Inflammatory Responses. AB - Toll-like receptors (TLRs) are major receptors of the host innate immune system that recognize conserved pathogen-associated molecular patterns (PAMPs) of invading microbes. Activation of TLR signaling culminates in the expression of multiple genes in a coordinate and kinetically defined manner. In this review, we summarize the current studies describing the chromatin landscape of TLR responsive inflammatory genes and how changes to this chromatin landscape govern cell type-specific and temporal gene expression. We further elaborate classical endotoxin tolerance and epigenetic mechanisms controlling tolerance and interferon priming effects on inflammatory promoters. PMID- 27379870 TI - Holistic processing of face configurations and components. AB - Although many researchers agree that faces are processed holistically, we know relatively little about what information holistic processing captures from a face. Most studies that assess the nature of holistic processing do so with changes to the face affecting many different aspects of face information (e.g., different identities). Does holistic processing affect every aspect of a face? We used the composite task, a common means of examining the strength of holistic processing, with participants making same-different judgments about configuration changes or component changes to 1 portion of a face. Configuration changes involved changes in spatial position of the eyes, whereas component changes involved lightening or darkening the eyebrows. Composites were either aligned or misaligned, and were presented either upright or inverted. Both configuration judgments and component judgments showed evidence of holistic processing, and in both cases it was strongest for upright face composites. These results suggest that holistic processing captures a broad range of information about the face, including both configuration-based and component-based information. (PsycINFO Database Record PMID- 27379869 TI - Chromatin Landscape of the IRF Genes and Role of the Epigenetic Reader BRD4. AB - Histone post-translational modification patterns represent epigenetic states of genomic genes and denote the state of their transcription, past history, and future potential in gene expression. Genome-wide chromatin modification patterns reported from various laboratories are assembled in the ENCODE database, providing a fertile ground for understanding epigenetic regulation of any genes of interest across many cell types. The IRF family genes critically control innate immunity as they direct expression and activities of interferons. While these genes have similar structural and functional traits, their chromatin landscapes and epigenetic features have not been systematically evaluated. Here, by mining ENCODE database using an imputational approach, we summarize chromatin modification patterns for 6 of 9 IRF genes and show characteristic features that connote their epigenetic states. BRD4 is a BET bromodomain protein that "reads and translates" epigenetic marks into transcription. We review recent findings that BRD4 controls constitutive and signal-dependent transcription of many genes, including IRF genes. BRD4 dynamically binds to various genomic genes with a spatial and temporal specificity. Of particular importance, BRD4 is shown to critically regulate IRF-dependent anti-pathogen protection, inflammatory responses triggered by NF-kappaB, and the growth and spread of many cancers. The advent of small molecule inhibitors that disrupt binding of BET bromdomain to acetylated histone marks has opened new therapeutic possibilities for cancer and inflammatory diseases. PMID- 27379871 TI - Priming stress patterns in word recognition. AB - This study addresses the lexical representation of stress in a series of 5 intramodal and cross-modal priming experiments in the Greek language using lexical decision tasks with auditory and visual targets. Three-syllable primes and targets were matched in first syllable segments, length, and other variables, and differed segmentally in the second and third syllable. Primes matched or mismatched targets in stress, which was placed on the penultimate or antepenultimate syllable. There was no evidence for stress priming in either accuracy or latency of responses to either words or pseudowords in any of these experiments, either intramodally or cross-modally. In contrast, a control fragment priming experiment using only the first 2 syllables of the primes produced a significant effect of stress congruence for words but not for pseudowords. The results are interpreted in the context of previous findings in the literature as arising from lexical activation rather than from matching stress patterns. Overall, findings are consistent with lexical representations including stress information that is inseparable from segmental specification, rather than with abstract representations of metrical templates. (PsycINFO Database Record PMID- 27379872 TI - Listeners lengthen phrase boundaries in self-paced music. AB - Previous work has shown that musicians tend to slow down as they approach phrase boundaries (phrase-final lengthening). In the present experiments, we used a paradigm from the action perception literature, the dwell time paradigm (Hard, Recchia, & Tversky, 2011), to investigate whether participants engage in phrase boundary lengthening when self-pacing through musical sequences. When participants used a key press to produce each successive chord of Bach chorales, they dwelled longer on boundary chords than nonboundary chords in both the original chorales and atonal manipulations of the chorales. When a novel musical sequence was composed that controlled for metrical and melodic contour cues to boundaries, the dwell time difference between boundaries and nonboundaries was greater in the tonal condition than in the atonal condition. Furthermore, similar results were found for a group of nonmusicians, suggesting that phrase-final lengthening in musical production is not dependent on musical training and can be evoked by harmonic cues. PMID- 27379873 TI - Dissociation of local and global contributions to detection of shape with age. AB - Radial Frequency (RF) patterns are a useful stimulus for assessing sensitivity to changes in shape. With these patterns it is possible to separate sensitivity to local curvature information from the ability to globally integrate information around the contour. Previous work has demonstrated that young, school-age children are less sensitive to deformation in RF patterns than adults. However, since the efficiency of contour integration was not assessed, age-related differences in performance could arise from either changes in the strength of global pooling of information, the sensitivity to local curvature information, or both. In this study, psychophysical methods were used to reassess changes in sensitivity to RF patterns, separating changes in sensitivity to local curvature information from changes in contour integration strength. Typically developing observers (aged 6-24, N = 104) were tested using a 2-alternative forced-choice discrimination task with either 1, 2 or 3 cycles of sinusoidal modulation in a pattern of fixed RF. Thresholds were lower for older observers but the rate of change, as more modulation cycles were added, was approximately constant across age. The results indicate that changes in sensitivity to RF3 patterns across age are due to changes in local curvature sensitivity and not to the strength of contour integration. (PsycINFO Database Record PMID- 27379874 TI - Distinct information critically distinguishes judgments of face familiarity and identity. AB - Accurately determining the familiarity of another and correctly establishing their identity are vital social skills. A considerable body of work has explored their perceptual and neural underpinnings and debate remains regarding whether they are dissociable, that is, separable parts of a dual process, or different aspects of a common retrieval process. Less is known about the specific visual information that guides familiarity judgments and how this compares to the information used to identify a face by name. Here we sought to establish the critical information underlying participants' judgments of facial familiarity and identification. We created a new standardized stimulus set comprising 6 personally familiar and 12 unfamiliar faces and applied the Bubbles reverse correlation methodology to establish the information driving correct performance in each task. Results revealed that markedly different information underlies familiarity and identity judgments. When categorizing familiarity, participants relied more upon lower spatial-frequency, broad facial cues (eye and face shape) than when categorizing identity, which relied on fine details in the internal features (eyes and mouth). These results provide novel evidence of qualitatively distinct information use in familiarity and identification judgments and emphasize the importance of considering the task set for participants and their processing strategy when investigating face recognition. (PsycINFO Database Record PMID- 27379875 TI - Effect of non-alcoholic fatty liver disease on left ventricular diastolic function and geometry in the Korean general population. AB - AIM: Previous studies showed that non-alcoholic fatty liver disease (NALFD) could be related to subclinical left ventricular (LV) diastolic dysfunction and remodeling. However, this association is still equivocal in the general population. Thus, this study was carried out to examine whether NAFLD is associated with the risk for LV diastolic dysfunction and remodeling. METHODS: A cross-sectional study was carried out for 20 821 Korean men and women who received a health checkup including echocardiography from 2011 to 2012. The study population was divided into three groups of normal, mild and moderate-to-severe NAFLD detected by ultrasonography. Using multivariable logistic regression analysis, the odd ratios of abnormal LV relaxation and remodeling were analyzed according to the degree of NAFLD. Additionally, adjusted mean values of LV diastolic functional and structural parameters were evaluated in the three groups. RESULTS: Compared with the normal group, the mild and moderate-to-severe NAFLD groups had higher odd ratios for abnormal LV relaxation (mild group 1.29, 95% confidence interval 1.15-1.46; moderate-to-severe group 1.95, 95% confidence interval 1.61-2.35) and increased relative wall thickness (>0.42; mild group 1.26, 95% confidence interval 1.05-1.52; moderate-to-severe group 1.46, 95% confidence interval 1.08-1.95). Analyzing adjusted mean values of LV parameters also showed the significant association between the degree of NAFLD and impaired LV diastolic function and concentric LV remodeling. CONCLUSIONS: The risk for LV diastolic dysfunction and remodeling proportionally increased according to the degree of NAFLD. NAFLD is significantly associated with LV functional and structural alteration. PMID- 27379876 TI - [Not Available]. PMID- 27379877 TI - [Not Available]. PMID- 27379879 TI - [Not Available]. PMID- 27379878 TI - [Not Available]. PMID- 27379880 TI - [Not Available]. PMID- 27379882 TI - [Not Available]. PMID- 27379881 TI - [Not Available]. PMID- 27379883 TI - [Not Available]. PMID- 27379884 TI - Medical Toxicology and Public Health-Update on Research and Activities at the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry : Environmental Exposures among Arctic Populations: The Maternal Organics Monitoring Study in Alaska. AB - Evidence suggests that in-utero exposure to environmental chemicals, such as persistent organic pollutants (POPs), heavy metals, and radionuclides, that might bioaccumulate in the mother may increase a newborn's risk of adverse developmental, neurological, and immunologic effects. Chemical contamination of bodies of water and strong ocean currents worldwide can drive these chemicals from lower latitudes to Arctic waters where they accumulate in common traditional subsistence foods. In response to concerns of the people from Alaska of the effects of bio-accumulated chemicals on their children, the Maternal Organics Monitoring Study(MOMS) was developed. The objective of the study was to assess the risks and benefits associated with the population's subsistence diet. Data analysis of biological samples at the CDC's NCEH laboratory and maternal questionnaires is ongoing. Results will be provided to Alaska Native communities to help support public health actions and inform future interventions and research. PMID- 27379885 TI - Prophylactic immunotherapy of Alzheimer's disease using recombinant amyloid-beta B-cell epitope chimeric protein as subunit vaccine. AB - Alzheimer's disease (AD) is a neurodegenerative disorder that impairs memory and cognition. The neuropathological features of the disease include senile plaques (SPs), neurofibrillary tangles (NFTs) and neuronal loss in affected brain regions. The amyloid cascade hypothesis suggests that production and accumulation of excessive amyloid-beta (Abeta) may be the main cause in the onset and progression of Alzheimer's disease. Active and passive immunotherapy targeting Abeta may be the most promising strategy to prevent or treat AD. This commentary focuses on the prophylactic immunotherapy of Alzheimer's disease using recombinant Abeta B-cell epitope chimeric protein as subunit vaccine targeting amyloid-beta. We discuss the efficiency and perspective of this type of recombinant subunit protein vaccine and suggest a novel direction on the path to a successful AD immunotherapy. This novel chimeric protein immunogen as subunit vaccine of AD may be designed to mimic the assembly states of Abeta42 or oligomers using multivalent foldable Abeta1-15 (B cell epitopes of Abeta42) and foreign T helper (Th) epitopes (as the T cell epitopes of Abeta42) constructs. PMID- 27379886 TI - Development of a Subject-Specific Foot-Ground Contact Model for Walking. AB - Computational walking simulations could facilitate the development of improved treatments for clinical conditions affecting walking ability. Since an effective treatment is likely to change a patient's foot-ground contact pattern and timing, such simulations should ideally utilize deformable foot-ground contact models tailored to the patient's foot anatomy and footwear. However, no study has reported a deformable modeling approach that can reproduce all six ground reaction quantities (expressed as three reaction force components, two center of pressure (CoP) coordinates, and a free reaction moment) for an individual subject during walking. This study proposes such an approach for use in predictive optimizations of walking. To minimize complexity, we modeled each foot as two rigid segments-a hindfoot (HF) segment and a forefoot (FF) segment-connected by a pin joint representing the toes flexion-extension axis. Ground reaction forces (GRFs) and moments acting on each segment were generated by a grid of linear springs with nonlinear damping and Coulomb friction spread across the bottom of each segment. The stiffness and damping of each spring and common friction parameter values for all springs were calibrated for both feet simultaneously via a novel three-stage optimization process that used motion capture and ground reaction data collected from a single walking trial. The sequential three-stage process involved matching (1) the vertical force component, (2) all three force components, and finally (3) all six ground reaction quantities. The calibrated model was tested using four additional walking trials excluded from calibration. With only small changes in input kinematics, the calibrated model reproduced all six ground reaction quantities closely (root mean square (RMS) errors less than 13 N for all three forces, 25 mm for anterior-posterior (AP) CoP, 8 mm for medial lateral (ML) CoP, and 2 N.m for the free moment) for both feet in all walking trials. The largest errors in AP CoP occurred at the beginning and end of stance phase when the vertical ground reaction force (vGRF) was small. Subject-specific deformable foot-ground contact models created using this approach should enable changes in foot-ground contact pattern to be predicted accurately by gait optimization studies, which may lead to improvements in personalized rehabilitation medicine. PMID- 27379888 TI - [Not Available]. PMID- 27379887 TI - Patient-Reported Safety Information: A Renaissance of Pharmacovigilance? AB - The role of patients as key contributors in pharmacovigilance was acknowledged in the new EU pharmacovigilance legislation. This contains several efforts to increase the involvement of the general public, including making patient adverse drug reaction (ADR) reporting systems mandatory. Three years have passed since the legislation was introduced and the key question is: does pharmacovigilance yet make optimal use of patient-reported safety information? Independent research has shown beyond doubt that patients make an important contribution to pharmacovigilance signal detection. Patient reports provide first-hand information about the suspected ADR and the circumstances under which it occurred, including medication errors, quality failures, and 'near misses'. Patient-reported safety information leads to a better understanding of the patient's experiences of the ADR. Patients are better at explaining the nature, personal significance and consequences of ADRs than healthcare professionals' reports on similar associations and they give more detailed information regarding quality of life including psychological effects and effects on everyday tasks. Current methods used in pharmacovigilance need to optimise use of the information reported from patients. To make the most of information from patients, the systems we use for collecting, coding and recording patient-reported information and the methodologies applied for signal detection and assessment need to be further developed, such as a patient-specific form, development of a severity grading and evolution of the database structure and the signal detection methods applied. It is time for a renaissance of pharmacovigilance. PMID- 27379889 TI - Prognostic and predictive value of the novel classification of lung adenocarcinoma in patients with stage IB. AB - PURPOSE: Controversy remains exist for the effect of adjuvant chemotherapy (ACT) among stage IB lung adenocarcinoma patients. This study aimed to investigate the predictive value of the current lung adenocarcinoma classification system on benefit of ACT among patients with stage IB lung adenocarcinoma. METHODS: A total of 928 pathological stage IB invasive adenocarcinoma patients with R0 resection were included in this study. Based on the predominant growth pattern present in the tumor, invasive adenocarcinomas with mixed histologic components were classified into five subtypes: lepidic (LEP), acinar (ACN), papillary (PAP), micropapillary (MIP) and solid (SOL). These five histologic subtypes were collapsed into three groups (LEP, ACN/PAP and SOL/MIP). Disease-free survival (DFS) and overall survival (OS) were analyzed to evaluate benefit from ACT in patients with different histologic patterns using the Kaplan-Meier approach and multivariable Cox models. RESULTS: For all stage IB invasive adenocarcinoma patients, SOL/MIP subgroup presented the worst prognosis, and LEP subgroup showed approximately 100 % 5-year survival. ACT was associated with a better DFS (HR, 0.70; 95 % CI 0.51-0.96, p = .026) for all stage IB patients. In SOL/MIP subgroup, patients could benefit from ACT for a significant improved DFS (HR, 0.81; 95 % CI 0.49-1.35; p = .030), but not for OS (HR, 0.39; 95 % CI 0.12-1.30, p = .111). In ACN/PAP subgroup, there was no significant benefit from ACT for both DFS (HR, 0.76; 95 % CI 0.54-1.08, p = .125) and OS (HR, 0.81; 95 % CI 0.49 1.35, p = .421). CONCLUSIONS: SOL/MIP predominant pattern was predictive for ACT benefit for DFS among invasive lung adenocarcinoma patients in stage IB. PMID- 27379890 TI - A new validated score for detecting patient-reported success on postoperative ICIQ-SF: a novel two-stage analysis from two large RCT cohorts. AB - INTRODUCTION AND HYPOTHESIS: The Patient Global Impression of Improvement (PGI-I) and International Consultation of Incontinence Questionnaire - Short Form (ICIQ SF) are validated instruments for the assessment of patient reported outcome measures (PROM) following treatment of stress urinary incontinence (SUI). However, there is a paucity of evidence as to what represents a successful postintervention ICIQ-SF score. To determine the correlation between the postoperative ICIQ-SF scores with the PGI-I outcomes, the latter was considered one of the standard PROM following surgical treatment for SUI. The aim of this study was to determine, and if appropriate validate, an ICIQ-SF cut-off score that can predict a successful PROM as determined by PGI-I. METHODS: Four large datasets yielding 674 ICIQ-SF score/PGI-I outcome data pairs were used in this study for (a) determining and (b) validating the cut-off ICIQ-SF score for a successful PGI-I outcome. Two long-term follow-up datasets were used representing follow-up periods of 3 and 8 years of a randomized controlled trial (RCT) performed between April 2005 and April 2007 in a tertiary urogynaecology centre in Scotland, UK. All patients had urodynamic SUI or mixed urinary incontinence (MUI, with predominant SUI) and were randomized to treatment with either an inside-out or an outside-in transobturator tape (TVT-O or TOT, respectively) as a sole procedure. The datasets yielded 432 ICIQ-SF score/PGI-I outcome data pairs. Successful outcome was defined as "very much improved/much improved" on the PGI-I scale. SPSS v. 22.0 (IBM Corp., Armonk, NY) was used for all statistical analyses. The correlations and cut-off scores generated were then validated on two independent datasets representing the 1-year and 4-year follow-up periods of the multicentre RCT in six units in the UK. The datasets yielded 242 ICIQ-SF score/PGI-I outcome data pairs. All patients had urodynamic SUI or MUI (with predominant SUI) and were randomized to either adjustable single incision minisling (SIMS) or TVT-O. RESULTS: Significant correlations at the 0.01 level (two-tailed) were clearly demonstrated between ICIQ-SF scores at follow up and PGI-I outcomes in terms of success/failure in both the generation and validation datasets. Higher ICIQ-SF scores correlated with a 'poorer' PGI-I score. Using ROC analysis, a postoperative ICIQ-SF score of 6 was validated as approximately 90 % sensitive and 85 % specific for success/failure with a high Cohen's kappa coefficient of 0.83 (95 % CI 0.74 - 0.89). CONCLUSIONS: This two-stage study provided a robust well-validated postoperative ICIQ-SF cut-off score (of 6/21) that is likely to be associated with a patient-reported successful outcome on the PGI-I following surgical treatment with a midurethral sling in women at different stages of follow-up over 1 - 8 years. Such a cut-off score could enable the comparison of results between various studies and serve as a valuable guide for surgeons to counsel patients before and/or after surgical treatment. Our study fills a research gap in providing a way to compare trial results when baseline ICIQ-SF scores are not available. PMID- 27379893 TI - Correction: Patterns of Freshwater Species Richness, Endemism, and Vulnerability in California. AB - [This corrects the article DOI: 10.1371/journal.pone.0130710.]. PMID- 27379892 TI - Native-tissue repair of isolated primary rectocele compared with nonabsorbable mesh: patient-reported outcomes. AB - INTRODUCTION: We evaluated patient-reported outcomes and complications after treatment of isolated primary rectocele in routine health-care settings using native-tissue repair or nonabsorbable mesh. METHODS: We used prospective data from the Swedish National Register for Gynaecological Surgery and included 3988 women with a primary operation for rectocele between 2006 and 2014: 3908 women had native-tissue repair, 80 were operated with nonabsorbable mesh. No concurrent operations were performed. Pre- and perioperative data were collected from doctors and patients. Patient-reported outcomes were evaluated 2 and 12 months after the operation. Only validated questionnaires were used. RESULTS: One year after native-tissue repair, 77.8 % (76.4-79.6) felt they were cured, which was defined as never or hardly ever feeling genital protrusion; 74.0 % (72.2-75.7) were very satisfied or satisfied, and 84 % (82.8-85.9) reported improvement of symptoms. After mesh repair, 89.8 % (77.8-96.6) felt cured, 69.2 % (54.9-81.3) were very satisfied or satisfied, and 86.0 % (72.1-94.7) felt improvement. No significant differences were found between groups. Organ damage was found in 16 (0.4 %) patients in the native-tissue repair group compared with one (1.3 %) patient in the mesh group [odds ratio (OR) 3.08; 95 % confidence interval (CI) 0.07-20.30]. The rate of de novo dyspareunia after native-tissue repair was 33.1 % (30.4-35.8), comparable with that after mesh repair. The reoperation rate was 1.1 % (0.8-1.5) in both groups. CONCLUSION: Most patients were cured and satisfied after native-tissue repair of the posterior vaginal wall, and the patient-reported outcomes were comparable with results after mesh repair. The risk of serious complications and reoperation were comparable between groups. PMID- 27379891 TI - Recurrent pelvic organ prolapse: International Urogynecological Association Research and Development Committee opinion. AB - INTRODUCTION AND HYPOTHESIS: This committee opinion paper summarizes available evidence about recurrent pelvic organ prolapse (POP) to provide guidance on management. METHOD: A working subcommittee from the International Urogynecological Association (IUGA) Research and Development Committee was formed. The literature regarding recurrent POP was reviewed and summarized by individual members of the subcommittee. Recommendations were graded according to the 2009 Oxford Levels of Evidence. The summary was reviewed by the Committee. RESULTS: There is no agreed definition for recurrent POP and evidence in relation to its evaluation and management is limited. CONCLUSION: The assessment of recurrent POP should entail looking for possible reason(s) for failure, including persistent and/or new risk factors, detection of all pelvic floor defects and checking for complications of previous surgery. The management requires individual evaluation of the risks and benefits of different options and appropriate patient counseling. There is an urgent need for an agreed definition and further research into all aspects of recurrent POP. PMID- 27379894 TI - The influence of facial sex cues on emotional expression categorization is not fixed. AB - The speed of recognizing facial expressions of emotion is influenced by a range of factors including other concurrently present facial attributes, like a person's sex. Typically, when participants categorize happy and angry expressions on male and female faces, they are faster to categorize happy than angry expressions displayed by females, but not displayed by males. Using the same emotional faces across tasks, we demonstrate that this influence of sex cues on emotion categorization is dependent on the other faces recently encountered in an experiment. Altering the salience of gender by presenting male and female faces in separate emotion categorization tasks rather than together in a single task changed the influence of sex cues on emotion categorization, whereas changing the evaluative dimension by presenting happy and angry expressions in separate tasks alongside neutral faces rather than together within 1 task did not. These results suggest that the way facial attributes influence emotion categorization depends on the situation in which the faces are encountered and specifically on what information is made salient within or across tasks by other recently encountered faces. (PsycINFO Database Record PMID- 27379895 TI - Proximal gastrectomy with exclusion of no. 3b lesser curvature lymph node dissection could be indicated for patients with advanced upper-third gastric cancer. AB - BACKGROUND: Proximal gastrectomy has been introduced for early gastric cancer located in the upper third of the stomach, but expansion of its indication to advanced tumors has not been generally accepted in terms of lesser curvature lymph node dissection. METHODS: We reviewed the medical records of 385 patients with tumors in the upper third of the stomach, and the incidence of metastasis and the therapeutic index related to the proximal (no. 3a) and distal (no. 3b) lymph nodes of the lesser curvature were analyzed and compared with those of tumors in the middle third (n = 1093) and lower third (n = 922) of the stomach. RESULTS: The no. 3a rate of metastasis from advanced tumors in the upper third of the stomach was significantly higher than that from tumors in the middle third or lower third of the stomach. The no. 3b metastasis rate did not show any significant differences between the three locations, but the therapeutic index of no. 3b lymph nodes in the upper third of the stomach (1.7) was far lower than that in the middle third (7.1) or lower third (7.0). Further, the rate of metastasis from tumors with the distal border ending in the upper third of the stomach (2.2 %) was significantly (P < 0.0001) lower than that from tumors located in the upper third of the stomach but extending to the middle third (19.6 %), as well as from tumors located in middle third (17.1 %) or lower third (19.6 %), with the therapeutic index being only 1.1. The four no.-3b-positive tumors all measured more than 40 mm, and included one T3 tumor and three T4 tumors. CONCLUSION: Proximal gastrectomy with exclusion of no. 3b lymphadenectomy could be indicated for at least T2 tumors measuring less than 40 mm localized in the upper third of the stomach. PMID- 27379896 TI - A Rare Cause of Myoclonus: A Cupric Conundrum. AB - A woman aged 22 years presented with a 3-year history of jerks when brushing her teeth and a tremor when carrying drinks. Examination revealed a bilateral jerky tremor, stimulus-sensitive myoclonus, and difficulty with tandem gait. Thyroid and liver function test results were normal, but she had rapidly progressive renal failure. Serum copper, ceruloplasmin, and manganese levels were normal, but her urinary copper level was elevated on 2 occasions. Pathological findings on organ biopsy prompted genetic testing to confirm the diagnosis. The differential diagnosis, tissue biopsy findings, and final genetic diagnosis are discussed. PMID- 27379897 TI - Retinal regeneration in birds and mice. AB - Retinal regeneration from resident Muller glia cells is robust in teleost fish, but is severely limited in birds and mammals. After neurotoxic injury, chick Muller glia can proliferate, and activate neurogenic genes, but they display limited capacity to differentiate into neurons. Developmental signaling molecules enhance this process. Regeneration of retinal neurons in rodents is even more limited. However, studies show evidence of proliferation and neurogenic gene expression after injury, with stronger effects in rats than mice, and differences between mouse strains. Mitogenic growth factors and Wnt signaling potentiate the proliferative response, while misexpression of the proneural transcription factor, Ascl1, reprograms to generate neurons from Muller glial in vitro, and stimulates neuronal regeneration in young mice, in vivo. PMID- 27379898 TI - The interstitial stem cells in Hydractinia and their role in regeneration. AB - Hydractinia species have been animal models in developmental biology and comparative immunology for over a century, but are having a renaissance due to the establishment of modern genetic and genomic tools by the growing community of researchers utilizing them. Hydractinia has a predictable and accessible life cycle and its stem cell system, known as interstitial- or i-cells has been a paradigm for animal stem cells since the late 1800s. In adult Hydractinia, i cells continuously provide progenitors to sustain clonal growth, tissue homeostasis, sexual reproduction and regeneration. We review recent developments in stem cell and regeneration research centered on this animal. Hydractinia joins an established team of cnidarian genetic models in times of rapid progress in these disciplines. While each animal is particularly suited to specific experimental settings, jointly they can provide an integrative insight into the diversity of animal stem cell systems, how they drive regeneration, and how they evolved. PMID- 27379899 TI - (Neo)blast from the past: new insights into planarian stem cell lineages. AB - Collectively, planarian stem cells (neoblasts) are totipotent and are required for tissue homeostasis and regeneration. Recent work has begun to test the long standing question of whether all neoblasts have the same potential, or whether they actually represent molecularly distinct subpopulations with distinct tissue restriction. Here, we summarize the current state of the field in neoblast lineage organization. It is clear that at least some neoblasts are totipotent, whereas other neoblasts represent functionally distinct molecular subclasses with restricted potential. In addition to neoblast subclasses, tissue-specific progenitors have also been identified, though their ability to proliferate is largely unknown. Together, neoblast lineage development, subclasses, and cell hierarchies are becoming elucidated, showing the complex regulation required for proper tissue homeostasis and regeneration in planarians. PMID- 27379900 TI - Colonial ascidians as model organisms for the study of germ cells, fertility, whole body regeneration, vascular biology and aging. AB - Colonial ascidians are marine invertebrate chordates that are the closest invertebrate relative to the vertebrates. Colonies of Botryllus schlosseri undergo a continuous asexual reproduction process that involves the regeneration of entire new bodies, which include all somatic and germline tissues. This adult regenerative process depends on signaling pathways known to regulate the formation of tissues and organs during embryonic development. The formation of gonads within regenerated bodies depends on migration and homing of germ cell precursors to niches within the developing bodies, and Botryllus colonies can cycle between fertile and infertile states. The vasculature that connects all individuals within the colony is highly regenerative, and is a valuable tool for the study of angiogenesis in adult blood vessels. The tremendous regenerative capacity of the vasculature even results in regeneration of entire new bodies solely from fragments of blood vessels upon surgical removal of all bodies. The mechanism underlying this regeneration of whole bodies is not well understood, but appears to depend on proliferation of circulating, blood borne cells. Because of all of these features, colonial ascidians are ideal model organisms for the study of germ cell migration, fertility, vascular biology and regeneration. PMID- 27379901 TI - Co-option during the evolution of multicellular and developmental complexity in the volvocine green algae. AB - Despite its major impact on the evolution of Life on Earth, the transition to multicellularity remains poorly understood, especially in terms of its genetic basis. The volvocine algae are a group of closely related species that range in morphology from unicellular individuals (Chlamydomonas) to undifferentiated multicellular forms (Gonium) and complex organisms with distinct developmental programs and one (Pleodorina) or two (Volvox) specialized cell types. Modern genetic approaches, complemented by the recent sequencing of genomes from several key species, revealed that co-option of existing genes and pathways is the primary driving force for the evolution of multicellularity in this lineage. The initial transition to undifferentiated multicellularity, as typified by the extant Gonium, was driven primarily by the co-option of cell cycle regulation. Further morphological and developmental innovations in the lineage leading to Volvox resulted from additional co-option events involving genes important for embryonic inversion, asymmetric cell division, somatic and germ cell differentiation and the structure and function of the extracellular matrix. Because of their relatively low but variable levels of morphological and developmental complexity, simple underlying genetics and recent evolutionary history, the volvocine algae are providing significant insight into our understanding of the genetics and evolution of major developmental and morphological traits. PMID- 27379902 TI - Predicting Endurance Time in a Repetitive Lift and Carry Task Using Linear Mixed Models. AB - OBJECTIVES: Repetitive manual handling tasks account for a substantial portion of work-related injuries. However, few studies report endurance time in repetitive manual handling tasks. Consequently, there is little guidance to inform expected work time for repetitive manual handling tasks. We aimed to investigate endurance time and oxygen consumption of a repetitive lift and carry task using linear mixed models. METHODS: Fourteen male soldiers (age 22.4 +/- 4.5 yrs, height 1.78 +/- 0.04 m, body mass 76.3 +/- 10.1 kg) conducted four assessment sessions that consisted of one maximal box lifting session and three lift and carry sessions. The relationships between carry mass (range 17.5-37.5 kg) and the duration of carry, and carry mass and oxygen consumption, were assessed using linear mixed models with random effects to account for between-subject variation. RESULTS: Results demonstrated that endurance time was inversely associated with carry mass (R2 = 0.24), with significant individual-level variation (R2 = 0.85). Normalising carry mass to performance in a maximal box lifting test improved the prediction of endurance time (R2 = 0.40). Oxygen consumption presented relative to total mass (body mass, external load and carried mass) was not significantly related to lift and carry mass (beta1 = 0.16, SE = 0.10, 95%CI: -0.04, 0.36, p = 0.12), indicating that there was no change in oxygen consumption relative to total mass with increasing lift and carry mass. CONCLUSION: Practically, these data can be used to guide work-rest schedules and provide insight into methods assessing the physical capacity of workers conducting repetitive manual handling tasks. PMID- 27379903 TI - Program design for incentivizing ignition interlock installation for alcohol impaired drivers: The Ontario approach. AB - INTRODUCTION: Drinking and driving is a major risk factor for traffic injuries. Although ignition interlocks reduce drinking and driving while installed, several issues undermine their implementation including delayed eligibility for installation, low installation once eligible, and a return to previous risk levels after de-installation. The Canadian province of Ontario introduced a "Reduced Suspension with Ignition Interlock Conduct Review" Program, significantly changing pre-existing interlock policy. The Program incentivizes interlock installation and an "early" guilty plea. It also attempts to reduce long-term recidivism through behavioural feedback and compliance-based removal. This evaluation is the first in assessing Program impact. METHODS: Ontario drivers with a first time alcohol-impaired driving conviction between July 1, 2005 and November 25, 2014 comprised the study cohort. Longitudinal analyses, using interrupted time series and Cox regression, were conducted in which exposure was the Program and the outcomes were ignition interlock installation (N=30,200), pre-trial elapsed time (N=30,200), and post-interlock recidivism (N=9326). RESULTS: After Program implementation, installation rates increased by 54% and pre-trial elapsed time decreased by 146 days. Results suggest no effect on post-interlock recidivism. CONCLUSIONS: Through an incentive-based design, this Program was effective at addressing two commonly cited barriers to interlock implementation- delayed eligibility for installation and low installation once eligible. Results reveal that installation rates are responsive not only to incentivization but also to other external factors, thus presenting an opportunity for policy makers to find unique ways to influence interlock uptake, and thereby, to extend their deterrent effects to a larger subset of the population. This study is one of the few that do not rely on proxy measures of installation rate. PMID- 27379904 TI - Effects of Moderate and Vigorous Exercise on Nonalcoholic Fatty Liver Disease: A Randomized Clinical Trial. AB - IMPORTANCE: Nonalcoholic fatty liver disease (NAFLD) is a prevalent risk factor for chronic liver disease and cardiovascular disease. OBJECTIVE: To compare the effects of moderate and vigorous exercise on intrahepatic triglyceride content and metabolic risk factors among patients with NAFLD. DESIGN, SETTING, AND PARTICIPANTS: In this randomized clinical trial, participants with central obesity and NAFLD were recruited from community-based screening in Xiamen, China, from December 1, 2011, through December 25, 2013. Data analysis was performed from August 28, 2015, through December 15, 2015. INTERVENTIONS: Participants were randomly assigned to vigorous-moderate exercise (jogging 150 minutes per week at 65%-80% of maximum heart rate for 6 months and brisk walking 150 minutes per week at 45%-55% of maximum heart rate for another 6 months), moderate exercise (brisk walking 150 minutes per week for 12 months), or no exercise. MAIN OUTCOMES AND MEASURES: Primary outcome, change in intrahepatic triglyceride content measured by proton magnetic resonance spectroscopy at 6 and 12 months; secondary outcomes, changes in body weight, waist circumference, body fat, and metabolic risk factors. RESULTS: A total of 220 individuals (mean [SD] age, 53.9 [7.1] years; 149 woman [67.7%]) were randomly assigned to control (n = 74), moderate exercise (n = 73), and vigorous-moderate exercise (n = 73) groups. Of them, 211 (95.9%) completed the 6-month follow-up visit; 208 (94.5%) completed the 12-month follow up visit. Intrahepatic triglyceride content was reduced by 5.0% (95% CI, -7.2% to 2.8%; P < .001) in the vigorous-moderate exercise group and 4.2% (95% CI, -6.3% to -2.0%; P < .001) in the moderate exercise group compared with the control group at the 6-month assessment. It was reduced by 3.9% (95% CI, -6.0% to -1.7%; P < .001) in the vigorous-moderate exercise group and 3.5% (95% CI, -5.6% to 1.3%; P = .002) in the moderate exercise group compared with the control group at the 12-month assessment. Changes in intrahepatic triglyceride content were not significantly different between vigorous-moderate and moderate exercise at the 6- or 12-month assessment. Body weight, waist circumference, and blood pressure were significantly reduced in the vigorous-moderate exercise group compared with the moderate exercise and control groups at the 6-month assessment and in the vigorous-moderate and moderate exercise groups compared with the control group at the 12-month assessment. In addition, body fat was significantly reduced in the vigorous-moderate exercise group compared with the moderate exercise and control groups at the 12-month assessment. After adjusting for weight loss, the net changes in intrahepatic triglyceride content were diminished and became nonsignificant between the exercise and control groups (except for the moderate exercise group at the 6-month assessment). CONCLUSIONS AND RELEVANCE: Vigorous and moderate exercise were equally effective in reducing intrahepatic triglyceride content; the effect appeared to be largely mediated by weight loss. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01418027. PMID- 27379905 TI - A potential case of remission of Parkinson's disease. AB - We present the case of a 78-year-old male who, 16 years ago, was diagnosed with Parkinson's disease (PD) by a neurologist. He initially presented with left-hand tremor, stooped posture, shuffling gait, and frequent falls, which eventually progressed to bilateral motor symptoms after 3 years. Since 2012, his symptoms and signs have almost completely remitted, and he has been off all pharmacotherapy for that time. The accuracy of the initial PD diagnosis is supported by an appropriate clinical presentation, history of positive response to Sinemet, and an abnormal SPECT DaT scan; thus this case suggests the possibility of remission of symptoms in some patients. We propose that the patient's long history of meditation practice may have been one contributing factor of this improvement as meditation has been shown to release dopamine in the striatum. PMID- 27379906 TI - Recent advances in oncolytic adenovirus therapies for cancer. AB - Oncolytic adenoviruses (Onc.Ads) selectively replicate in and lyse cancer cells and are therefore commonly used vectors in clinical trials for cancer gene therapy. Building upon the well-characterized adenoviral natural tropism, genetic modification of Onc.Ad can enhance/regulate their transduction and replication within specific cancer cell types. However, Onc.Ad-mediated tumor cell lysis cannot fully eliminate tumors. The hostile tumor microenvironment provides many barriers to efficient oncolytic virotherapy, as tumors develop structure and immune-evasion mechanisms in order to grow and ultimately spread. For these reasons, Onc.Ads modified to deliver structural or immune modulatory molecules (Armed Onc.Ads) have been developed to overcome the physical and immunological barriers of solid tumors. The combination of oncolysis with tumor microenvironment modulation/destruction may provide a promising platform for Ad based cancer gene therapy. PMID- 27379907 TI - Early Life Predictors of Socio-Emotional Development in a Sample of Egyptian Infants. AB - INTRODUCTION: Emotional problems are amongst the most critical concerns to be intentionally handled to enhance the wellbeing and development of children. OBJECTIVE: To determine the predictors of socio-emotional development of Egyptian infants related to infant feeding practices, aspects of infant and maternal health and socioeconomic status. SUBJECTS AND METHODS: A cross-sectional comparative study included 322 breast fed, 240 bottle fed and 93 mixed fed infants, from 6-24 months of age, who were enrolled in the Well-Baby Clinic of the National Research Centre and from pediatric outpatient facilities in urban Cairo. Assessment of socio-emotional development was performed using Bayley Scales of Infant and Toddler Development (Bayley III). Detailed maternal and infant history was recorded. Levels of serum zinc, copper, iron, vitamin B12 and complete blood count (CBC) were assessed in a subsample of 193 infants. RESULTS: The risk of having below average socio-emotional composite score was nearly two and half times among formula-fed infants than among breast-fed infants. By binary logistical regression analysis, predictors of below average socio-emotional score were a lower serum zinc value, being formula fed during the first half-year and introduction of complementary food before the age of six months (p< 0.05). CONCLUSION: Exclusive breastfeeding and to a lesser extent mixed feeding during the first half year is correlated with above average socio-emotional development. Maternal education and zinc status were also determinants of better infant mental health. Our endeavors ought to be directed towards integrated interventions addressing multiple risks to children's development. PMID- 27379909 TI - Medical Observation Units and Emergency Department Collaboration: Improving Patient Throughput. AB - OBJECTIVE: The aim of this study was to identify whether observation status patients placed in a dedicated unit would decompress the emergency department (ED) more than observation patients who were admitted to other available beds. BACKGROUND: An urban quaternary hospital has a high volume of patients with average daily census of 95% capacity. A medical observation unit (MOU) was created to improve patient throughput. METHODS: In phase 1, the MOU charge nurse reviewed the ED patients to be admitted and selected appropriate patients based on unit inclusion criteria. In phase 2, the MOU charge nurse did rounds with the ED charge nurse once per shift. RESULTS: MOU observation patients demonstrated a 53-minute (16%) reduction in average overall ED length of stay compared with observation patients admitted to other units. CONCLUSION: Inclusion criteria, a rounding checklist, and engagement of MOU and ED nurses helped the MOU and ED with patient throughput. PMID- 27379908 TI - The Impact of an Integrated Electronic Health Record Adoption on Nursing Care Quality. AB - OBJECTIVES: The purpose of this study was to measure the impact of an integrated electronic health record (EHR) innovation adoption on the quality of nursing care delivered, including hospital-acquired falls, hospital-acquired pressure ulcers, ventilator-associated pneumonia (VAP), central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), and costs measured in nursing hours. The impact on quality, cost, and nurse satisfaction measured in turnover rates before, during, and after implementation of EHR tools was also investigated. BACKGROUND: Little is known about the adoption patterns of computerized documentation by nursing and the effects on the practice environment. METHODS: A quantitative, retrospective analysis using interrupted time series model of a large data set was conducted in a 431-bed urban hospital, with 10 medical surgical units and 2 critical care units. The research was constructed using the Diffusion of Innovations (DOI) theory. RESULTS: Incorporating electronic, evidenced-based practice (EBP) tools into bedside nurse's workflow promotes decision making at the point of care that may improve quality with no negative impact on direct cost. The data revealed that total falls, CAUTI, and CLABSI rates were positively impacted after the implementation of an integrated EHR. Hospital-acquired pressure ulcer and VAP rates were negatively impacted at the implementation period followed by a significant positive rate reduction that surpassed the preimplementation period. Cost indicators, measured in hours per patient day and overtime, were negatively impacted during the implementation period followed by a return to baseline. Nurse turnover had a significant increase from the preimplementation to postimplementation period and failed to return to baseline. CONCLUSIONS: This study confirms that nurses have the ability to positively impact the quality of patient care through successful innovation adoption related to the use of EBP computerized documentation tools at the bedside. This study further clarified the practice environment of nurses during DOI. PMID- 27379910 TI - Responding to Emotional Stress in Pediatric Hospitals: Results From a National Survey of Chief Nursing Officers. AB - OBJECTIVE: The aim of this study was to identify leadership awareness of emotional stress and employee support efforts in pediatric hospitals. BACKGROUND: The current pediatric environment has seen increases in treatment intensity, care duration, and acuity of patients resulting in increased likelihood of being exposed to emotional events. METHODS: Mail survey was sent to chief nursing officers at 87 pediatric hospitals. RESULTS: A total of 49 responses (56%) were received. Hospitals with less than 250 beds were significantly more likely to rate emotional stress as a large to very large problem, whereas ANCC Magnet(r) hospitals felt better about support efforts after patient deaths. Most commonly used support offerings focused on staff recovery after a traumatic event as opposed to training for prevention of emotional stress. CONCLUSIONS: Emotional stress is a well-recognized issue in pediatric hospitals with comparatively large resource commitment. Further focus on caregiver prevention training and unit leadership recognition of stress may be needed. PMID- 27379911 TI - Inhalation of a Short-Acting beta2-Adrenoreceptor Agonist Induces a Hypercoagulable State in Healthy Subjects. AB - BACKGROUND: Catecholamine infusion elicits an increase in clotting factors and this increase has been attributed to stimulation of beta2-adrenorecptors (beta2AR). Accordingly, we tested the hypothesis that inhalation of a short acting selective beta2AR agonist can induce a procoagulant state in healthy individuals. METHODS: We recruited 23 healthy volunteers (nine females; mean age: 26+/-0.8 years; body mass index: 24.7+/-0.5 kg/m2) and randomly allocated them into two groups, the beta2AR arm (seventeen subjects) and the saline arm (six subjects). Hemodynamics, plasma norepinephrine concentration, and procoagulant, anticoagulant, and fibrinolytic profiles of each participant were determined using specific assays before and after inhalation of either 2 mL nebulized normal saline or a mixture of 1 mL saline and 1 mL of salbutamol (5 mg salbutamol sulfate), a selective beta2AR agonist, which were delivered by a nebulizer over ten minutes. RESULTS: Saline inhalation had no effect on the procoagulant, anticoagulant and fibrinolytic profiles of the six healthy volunteer in the study's saline arm. Salbutamol inhalation caused (a) a significant increase in the activity or levels of the procoagulant factors; FVIII increased by 11+/-3% (p = 0.04), von Willebrand factor increased by 7+/-1% (p = 0.03), and (b) a significant decrease in the activated partial prothrombin time from 27.4+/-0.4 seconds to 25.5 +/-0.5 seconds (p<0.001) in the 17 volunteers in the study's beta2AR arm. D-dimer and prothrombin fragments F1+2 were elevated by 200 +/-90% and 505.0 +/-300.0%, respectively. In addition, the activity of the anticoagulant protein C pathway (demonstrated by the protein C Global assay) decreased from 1.0+/-0.08 to 0.82+/-0.06 (p<0.001). Although plasma levels of tissue plasminogen activator decreased, all other indices of the fibrinolytic system did not change following salbutamol inhalation. CONCLUSION: We found that a single inhalation of salbutamol, a short-acting beta2AR agonist, activates the clotting system without affecting the fibrinolytic system. This induction of a procoagulant state in healthy subjects warrants further investigation in patients treated with these agents. PMID- 27379912 TI - Using severity factor as a parameter to optimize krill treatment under subcritical water conditions. AB - The aim of this study was to optimize the conditions for subcritical water treatment of krill, as expressed with a single parameter: the severity factor (log R0). Raw krill was treated under subcritical water conditions at various log R0 values (1.54-3.75) by varying the treatment temperatures (120-180 degrees C) and times (0-10 min) in two different sizes of batch-type vessel (10 and 117 mL). The log R0 value could efficiently describe changes in various properties of the obtained liquid extracts and solid residues. The most desirable shrimp-like flavor intensity and highest sensory preference were obtained for log R0 values of 2.75-3.01. The results also proved that severity factor can be used as a single parameter to control subcritical water treatment conditions in differently sized batch-type vessels to produce shrimp-like flavor extract and residue from krill. PMID- 27379913 TI - In Vitro Antioxidant-Activity Evaluation of Gallic-Acid-Grafted Chitosan Conjugate Synthesized by Free-Radical-Induced Grafting Method. AB - The major objective of this work was to develop a green and facile process to prepare gallic acid-chitosan conjugate and comprehensively evaluate the physicochemical properties and biological activities of an as-prepared water soluble chitosan derivative. A free-radical-induced grafting approach using an ascorbic acid-hydrogen peroxide redox pair was adopted. The obtained conjugate was characterized by Fourier transform infrared spectroscopy, UV-vis, X-ray diffraction, and pKa analysis. The antioxidant activities were evaluated by 2,2 diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6) sulphonic acid (ABTS), reducing power, and oxygen-radical antioxidant-capacity assays. The results showed that the mass ratio of gallic acid to chitosan played a vital role in determining the grafting degree and zeta potential of the conjugates, with the ratio of 0.5:1 being the optimal ratio that resulted in the highest grafting degree. The antioxidant assays demonstrated that conjugation significantly improved the antioxidant activities, being dramatically higher than that of free chitosan. It was notable that the DPPH- and ABTS-scavenging activities of conjugate at 0.4 mg/mL reached the same level as the free gallic acid at the equivalent concentration. Our study demonstrated a green and facile synthesis approach to preparing a novel water-soluble chitosan derivative that may have promising potentials in the food industry. PMID- 27379914 TI - [Use of Complementary Medicine in Patients with Advanced Prostate Cancer: 2 Case Reports]. AB - Despite optimised diagnosis and treatment, prostate cancer can only be cured in a specific subset of patients. Advanced prostate cancer may lead to complications that severely impair the patient's quality of life, e. g. recurrent intravesical blood clotting due to local tumor necrosis. We report the successful use of the homeopathic remedy Thlaspi bursa pastoris in 2 patients for whom conventional treatment was not sufficiently effective. These case reports imply that complementary or alternative medical treatment may be an efficient adjunctive treatment in patients with advanced prostate cancer. PMID- 27379915 TI - Structured discharge instructions for hospitalized heart failure patients to improve guideline implementation and patient outcomes. PMID- 27379916 TI - Impact of postconditioning with lactate-enriched blood on in-hospital outcomes of patients with ST-segment elevation myocardial infarction. AB - BACKGROUND: Reperfusion injury offsets the beneficial effects of reperfusion therapy for ST-segment elevation myocardial infarction (STEMI). In our previous reports, postconditioning with lactate-enriched blood (PCLeB) induced excellent microcirculation recovery and less inflammation in STEMI patients. This study aimed to determine the in-hospital outcomes of STEMI patients treated using PCLeB. METHODS: Fifty-five consecutive STEMI patients were treated using PCLeB (Age 66.6+/-13.8years, 76.4% men) within 12h of symptom onset. In our modified postconditioning protocol, the duration of each brief reperfusion was prolonged from 10s to 60s in a stepwise manner. Lactated Ringer's solution (20-30mL) was injected directly into the culprit coronary artery at the end of each brief reperfusion and the balloon was quickly inflated at the lesion site, whereby lactate could be trapped inside the ischemic myocardium. Each brief ischemic period lasted 60s. After 7cycles of balloon inflation and deflation, full reperfusion was performed. Thereafter, stenting was performed and percutaneous coronary intervention (PCI) was completed. RESULTS: The mean corrected thrombolysis in myocardial infarction frame count was 20.1+/-10.1 after PCI completion. The mean peak serum creatine kinase and creatine kinase-MB levels were 2751+/-2227IU/L and 276+/-181IU/L respectively. None of the study patients died during their hospital stay or required continuation of oral diuretic or inotropic therapy for heart failure on discharge. CONCLUSIONS: PCLeB led to zero in-hospital mortality and no overt heart failure on discharge in 55 consecutive STEMI patients undergoing reperfusion therapy. PMID- 27379917 TI - An injectable capillary-like microstructured alginate hydrogel improves left ventricular function after myocardial infarction in rats. AB - BACKGROUND: A new post-myocardial infarction (MI) therapy is injection of high water-content polymeric biomaterial gels (hydrogels) into damaged myocardium to modulate cardiac negative remodeling and preserve heart function. METHODS: We investigated the therapeutic potential of a novel gelatinized alginate hydrogel with a unique microstructure of uniform capillary-like channels (termed Capgel). Shortly (48h) after induced anterior MI, Sprague Dawley rats received intramyocardial injection of Capgel directly into the antero-septal wall at the infarct border zone (n=12) or no injection (n=10, controls). Echocardiograms were performed at 48h (week 0) and 4weeks (week 4) to evaluate left ventricular function. RESULTS: Echocardiograms showed 27% improvement of left ventricular systolic function over time with gel injection: fractional shortening increased from 26+/-3% at week 0 to 33+/-2% at week 4 (p=0.001). Capgel was present at the injection site after 4weeks, but was minimal at 8weeks. The remaining gel was heavily populated by CD68(+) macrophages with CD206(+) clusters and blood vessels. An in vitro experiment was performed to assess Angiotensin-(1-7) released from Capgel. Angiotensin-(1-7) was released from the Capgel in a sustained manner for 90days. CONCLUSIONS: Use of Capgel, a degradable, bioactive hydrogel composed of gelatinized capillary-alginate gel, appears safe for intramyocardial injection, is associated with improved left ventricular function after MI in rats, and may provide a long-term supply of Angiotensin-(1-7). PMID- 27379918 TI - Infective endocarditis: Absence of microbiological diagnosis is an independent predictor of inhospital mortality. PMID- 27379919 TI - Impact of chronic kidney disease on clinical outcomes in patients with non-ST elevation myocardial infarction receiving percutaneous coronary intervention - A five-year observational study. AB - BACKGROUND: Patients with chronic kidney disease (CKD) experience poor outcomes after acute myocardial infarction. This study investigated how CKD affects clinical outcomes in patients with non-ST segment elevation myocardial infarction (NSTEMI) receiving PCI. METHODS: This retrospective study analyzed record-linked data for 314 patients who had received PCI for NSTEMI between January 2008 and September 2010. The 141 patients with advanced CKD were compared with 173 patients who had mild or no CKD. The primary endpoint was long-term mortality. The secondary endpoint was long-term major adverse cardiac events. RESULTS: Compared to the control group, the advanced CKD group had older patients, more females, and more patients with diabetes mellitus and hypertension. The advanced CKD group also had a lower left ventricular ejection fraction and more patients with advanced HF and pulmonary edema. The advanced CKD group and the control group did not significantly differ in total in-hospital mortality, cardiac death or temporary hemodialysis post-PCI. The advanced CKD group had a significantly higher rate of long-term events. Finally, multiple stepwise Cox regression analysis showed that old age, advanced CKD and advanced HF were independent predictors of primary endpoint. The best predictors of secondary endpoint were post-PCI Thrombolysis in Myocardial Infarction-3 flow, multiple vessel disease, advanced HF and advanced CKD. CONCLUSIONS: In NSTEMI patients undergoing PCI, in hospital mortality does not significantly differ between patients with and without advanced CKD. However, long-term follow up of CKD patients consistently reveals poor outcomes. PMID- 27379920 TI - A critical review on the translational journey of cardioprotective therapies! AB - The failure to translate novel cardioprotective therapies tested in pre-clinical studies into the clinical setting for patient benefit can be attributed to a number of factors at different stages of the research process. This review focuses on the evidences and the gaps with regard to the translational journey of cardioprotective interventions. Gaps are classified into 3 main groups: 1) those related to pre-clinical studies, 2) those associated with the validation of infarct size as a good surrogate and 3) those based on design and interpretation of randomized clinical trials on cardioprotection. Addressing these gaps might increase the chances to successfully translate cardioprotective therapies into improving both post-STEMI heart failure and cardiovascular death rates. PMID- 27379921 TI - Inhibition of intimal thickening after vascular injury with a cocktail of vascular endothelial growth factor and cyclic Arg-Gly-Asp peptide. AB - BACKGROUND: Percutaneous coronary intervention is widely used for the treatment of coronary artery disease; however, significant challenges such as restenosis remain. Key to solving these problems is to inhibit smooth muscle cell activation while enhancing re-endothelialization. Early growth response-1 (Egr-1) is a transcription factor that regulates vascular smooth muscle cell (SMC) proliferation and migration through its control of an array of downstream genes. METHODS: A "cocktail" of vascular endothelial growth factor (VEGF)-A, VEGF-D and cyclic RGD was tested for its ability to inhibit neointima formation and accelerate re-endothelialization following balloon injury to carotid arteries of rats. RESULTS: In vitro, the cocktail stimulated endothelial cell growth yet inhibited smooth muscle cell growth. In vivo, cocktail-treated injured arteries exhibited reduced intimal thickening by >50% (P<0.05). It increased both re endothelialization and endothelial nitric oxide synthase (NOS) expression. Cocktail reduced Egr-1 expression, an effect blocked by the NOS inhibitor L-N(G) nitroarginine methyl ester (L-NAME) that also prevented cocktail inhibition of neointima inhibition. CONCLUSIONS: This combination may potentially be useful for the treatment of restenosis with concomitant stimulation of revascularization. PMID- 27379922 TI - Effects of short-term administration of tolvaptan after open heart surgery. AB - BACKGROUND: Postoperative fluid overload following cardiac surgery is associated with increased morbidity and mortality. Unlike loop diuretics, tolvaptan (TLV) promotes aquaretic effect. Relatively little has been documented regarding the efficacy of TLV after cardiac surgery. The aim of the study was to investigate the effectiveness and safety of tolvaptan for the management of immediately postoperative fluid retention following cardiac surgery. METHODS: Between January to May 2014, patients undergoing cardiac surgery were randomly assigned to control or TLV group immediately after cardiac surgery. In control group, patients received 20mg of furosemide and 25mg of spironolactone as conventional diuretics. In the TLV group, 7.5mg of TLV was administered in combination with conventional diuretics. RESULTS: TLV use was associated with increased urine output from postoperative day 1 to 3.Body weight reduction in the TLV group was significantly greater than the control group from postoperative day 2 to 4, and serum creatinine levels decreased to below preoperative values in the TLV group. CONCLUSIONS: The combination of tolvaptan with conventional diuretics increases urine output without renal dysfunction and can be effective for postoperative fluid management and appropriate body weight reduction. PMID- 27379924 TI - Molecular Dynamics Simulation Study of Parallel Telomeric DNA Quadruplexes at Different Ionic Strengths: Evaluation of Water and Ion Models. AB - Most molecular dynamics (MD) simulations of DNA quadruplexes have been performed under minimal salt conditions using the Aqvist potential parameters for the cation with the TIP3P water model. Recently, this combination of parameters has been reported to be problematic for the stability of quadruplex DNA, especially caused by the ion interactions inside or near the quadruplex channel. Here, we verify how the choice of ion parameters and water model can affect the quadruplex structural stability and the interactions with the ions outside the channel. We have performed a series of MD simulations of the human full-parallel telomeric quadruplex by neutralizing its negative charge with K(+) ions. Three combinations of different cation potential parameters and water models have been used: (a) Aqvist ion parameters, TIP3P water model; (b) Joung and Cheatham ion parameters, TIP3P water model; and (c) Joung and Cheatham ion parameters, TIP4Pew water model. For the combinations (b) and (c), the effect of the ionic strength has been evaluated by adding increasing amounts of KCl salt (50, 100, and 200 mM). Two independent simulations using the Aqvist parameters with the TIP3P model show that this combination is clearly less suited for the studied quadruplex with K(+) as counterions. In both simulations, one ion escapes from the channel, followed by significant deformation of the structure, leading to deviating conformation compared to that in the reference crystallographic data. For the other combinations of ion and water potentials, no tendency is observed for the channel ions to escape from the quadruplex channel. In addition, the internal mobility of the three loops, torsion angles, and counterion affinity have been investigated at varied salt concentrations. In summary, the selection of ion and water models is crucial as it can affect both the structure and dynamics as well as the interactions of the quadruplex with its counterions. The results obtained with the TIP4Pew model are found to be closest to the experimental data at all of the studied ion concentrations. PMID- 27379923 TI - Neurohormonal activation and exercise tolerance in patients supported with a continuous-flow left ventricular assist device. AB - BACKGROUND: Neurohormones play a key role in regulating hemodynamics in heart failure (HF) both at rest and during exercise. In contrast, little is known about the importance of neurohormonal regulation for exercise capacity in continuous flow left ventricular assist device (CF-LVAD) patients. The aim of this study was to assess the relation between neurohormonal activation patterns in CF-LVAD patients and exercise capacity. METHODS: Plasma concentrations of the C-terminal portion of pro-arginine vasopressin precursor (copeptin), pro-adrenomedullin (proADM), pro-B-type (proBNP) and pro-atrial (proANP) natriuretic peptides were measured in 25 CF-LVAD patients (HeartMate II) in the morning prior to maximal cardiopulmonary exercise testing determining peak oxygen uptake (peak VO2). Quality of life (QOL) was determined by questionnaires. RESULTS: Peak VO2 was severely reduced averaging 13.0+/-5.3ml/kg/min and exhibited strong negative correlations with copeptin, r=-0.61 (p=0.001) and proADM, r=-0.56 (p=0.005). Additionally comparing patients with peak VO2<14 vs>=14ml/kg/min demonstrated significant differences in copeptin and proADM concentrations, 2.8+/-0.8 vs 2.1+/ 0.7pmol/l (p=0.03) and 1.0+/-0.5 vs 0.7+/-0.2nmol/l (p=0.01), respectively. In contrast natriuretic peptides were not associated with maximal exercise capacity. Lower QOL correlated with increasing proBNP. CONCLUSION: Resting plasma levels of proADM and copeptin are significantly correlated with peak VO2 in CF-LVAD patients. Future studies should address if interventions to lower the levels of these markers are associated with restoration of exercise tolerance. PMID- 27379925 TI - Diabetes: A Cinderella Subject We Can't Afford to Ignore. AB - In a Perspective, Juliana Chan and Andrea Luk discuss the impact of diabetes in countries around the world, setting the scene for a special issue on diabetes prevention comprising discussion pieces and research reports. PMID- 27379926 TI - Catastrophic Health Care Expenditure among Older People with Chronic Diseases in 15 European Countries. AB - INTRODUCTION: It is well-known that the prevalence of chronic diseases is high among older people, especially those who are poor. Moreover, chronic diseases can result in catastrophic health expenditure. The relationship between chronic diseases and their financial burden on households is thus double-sided, as financial difficulties can give rise to, and result from, chronic diseases. Our aim was to examine the levels of catastrophic health expenditure imposed by private out-of-pocket payments among older people diagnosed with diabetes mellitus, cardiovascular diseases and cancer in 15 European countries. METHODS: The SHARE dataset for individuals aged 50+ and their households, collected in 2010-2012 was used. The total number of participants included in this study was N = 51,661. The sample consisted of 43.8% male and 56.2% female participants. The average age was 67 years. We applied an instrumental variable approach for binary instrumented variables known as a treatment-effect model. RESULTS: We found that being diagnosed with diabetes mellitus and cardiovascular diseases was associated with catastrophic health expenditure among older people even in comparatively wealthy countries with developed risk-pooling mechanisms. When compared to the Netherlands (the country with the lowest share of out-of-pocket payments as a percentage of total health expenditure in our study), older people diagnosed with diabetes mellitus in Portugal, Poland, Denmark, Italy, Switzerland, Belgium, the Czech Republic and Hungary were more likely to experience catastrophic health expenditure. Similar results were observed for diagnosed cardiovascular diseases. In contrast, cancer was not associated with catastrophic health expenditure. DISCUSSION: Our study shows that older people with diagnosed chronic diseases face catastrophic health expenditure even in some of the wealthiest countries in Europe. The effect differs across chronic diseases and countries. This may be due to different socio-economic contexts, but also due to the specific characteristics of the different health systems. In view of the ageing of European populations, it will be crucial to strengthen the mechanisms for financial protection for older people with chronic diseases. PMID- 27379927 TI - Plasma vitamin D levels and inflammation in the aortic wall of patients with coronary artery disease with and without inflammatory rheumatic disease. AB - OBJECTIVES: Vitamin D modulates inflammation, and this may explain the observed associations between vitamin D status and disorders driven by systemic inflammation, such as coronary artery disease (CAD) and inflammatory rheumatic diseases (IRDs). The aims of this study were to assess vitamin D status in patients with CAD alone and in patients with CAD and IRD, and to explore potential associations between vitamin D status and the presence of mononuclear cell infiltrates (MCIs) in the aortic adventitia of these patients. METHOD: Plasma levels of 25-hydroxyvitamin D3 [(25(OH)D3] were determined by radioimmunoassay and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] by enzyme immunoassay in the 121 patients from the Feiring Heart Biopsy Study (FHBS) who had available histology data on adventitial MCIs; 53 of these had CAD alone and 68 had CAD and IRD. RESULTS: In the crude analysis, vitamin D levels were similar in CAD patients with and without IRD. After adjustment for potential confounders, IRD was associated with an increase of 8.8 nmol/L [95% confidence interval (CI) 1.0 16.6; p = 0.027] in 25(OH)D3 and an increase of 18.8 pmol/L (95% CI 4.3-33.3; p = 0.012) in 1,25(OH)2D3, while MCIs in the aortic adventitia were associated with lower levels of 1,25(OH)2D3 (beta = -18.8, 95% CI -33.6 to -4.0; p = 0.014). CONCLUSIONS: IRD was associated with higher levels of both 25(OH)D3 and 1,25(OH)2D3. These findings argue against the hypothesis that patients with high systemic inflammatory burden (CAD+IRD) should have lower vitamin D levels than those with less inflammation (CAD only). Of note, when controlled for potential confounders, low 1,25(OH)2D3 levels were associated with adventitial aortic inflammation. PMID- 27379928 TI - Fluoxetine Exhibits Pharmacological Effects and Trait-Based Sensitivity in a Marine Worm. AB - Global production of pharmacologically active compounds exceeds 100 000 tons annually, a proportion of which enters aquatic environments through patient use, improper medicine disposal, and production. These compounds are designed to have mode-of-action (MoA) effects on specific biological pathways, with potential to impact nontarget species. Here, we used MoA and trait-based approaches to quantify uptake and biological effects of fluoxetine, a selective serotonin reuptake inhibitor, in filter and deposit feeding marine worms (Hediste diversicolor). Worms exposed to 10 MUg L(-1), accumulated fluoxetine with a body burden over 270 times greater than exposure concentrations, resulting in ~10% increased coelomic fluid serotonin, a pharmacological effect. Observed effects included weight loss (up to 2% at 500 MUg L(-1)), decreased feeding rate (68% at 500 MUg L(-1)), and altered metabolism (oxygen consumption, ammonia excretion, and O/N from 10 MUg L(-1)). Bioconcentration of fluoxetine was dependent on route of uptake, with filter feeding worms experiencing up to 130 times greater body burden ratios and increased magnitudes of effects than deposit feeders, a trait based sensitivity likely as a consequence of fluoxetine partitioning to sediment. This study highlights how novel approaches such as MoA and trait-based methods can supplement environmental risk assessments of pharmaceuticals. PMID- 27379930 TI - Quality properties and adsorption behavior of freeze-dried beef meat from the Biceps femoris and Semimembranosus muscles. AB - The aim of this research was to determine the quality properties and adsorption behavior of freeze-dried beef meat from the Biceps femoris and Semimembranosus muscles. Most quality properties of both muscles were similar apart from total fat content. Freeze-dried meat pieces were kept in ten different equilibrium levels of relative humidity (2.0-97.3%) at 5, 15, 25 and 30 degrees C. The experimental data were evaluated using BET (Brunauer-Emmett-Teller) and GAB (Guggenheim, Anderson and deBoer) models. The equilibrium moisture contents of freeze-dried Biceps femoris were lower than those of Semimembranosus at all water activities and temperature. The constants m0 and C of BET and GAB equations were determined to be between 6.27 and 8.07g/100g dry matter and 9.32-13.73, respectively. Constant k was about 0.90 at all temperatures, and the GAB equation exhibited a better fit to the experimental data of both muscles as a result of all %E values being approximately equal to 10%. PMID- 27379931 TI - ESPE Position Statement for Paediatric Endocrinology Subspecialty. PMID- 27379932 TI - Diagnostic De L'Hypertension Arterielle. AB - Arterial hypertension is a very common disease, and one of the main causes of death in our countries. In the early stages, this disease is completely asymptomatic and thus the diagnosis can only be made by systematic examinations. How to treat, it is a problem which can only be solved if a certain amount of information is obtained. The physician must find out if other risk factors of atherosclerosis are involved: hypercholesterolemia, diabetes, cigarette smoking, etc. He must also look for complications of high blood pressure with respect to the heart, the kidneys, the arteries and the brain. All these parameters may affect the decision and the choice of the treatment. The first step of treatment must be the research for curable causes of hypertension. However, from data obtained during the last few years, we know that surgical causes of hypertension are unusual: less than 10% of the patients in a reference centre. In most of the case, the patient should be treated with drugs. PMID- 27379933 TI - The Management Of Hypertension - Back To Square One? PMID- 27379929 TI - KSP inhibitor SB743921 inhibits growth and induces apoptosis of breast cancer cells by regulating p53, Bcl-2, and DTL. AB - Kinesin spindle protein (KSP) is a microtubule-associated motor protein that is specifically expressed by mitosis cells. It is highly expressed in various types of tumors including hematomalignances and solid tumors. Chemical KSP inhibition has become a novel strategy in the development of anticancer drugs. SB743921 is a selective inhibitor for KSP, which is a mitotic protein essential for cell-cycle progression. Although SB743921 has shown antitumor activities for several types of cancers and entered into clinical trials, its therapeutic effects on breast cancer and mechanisms have not been explored. In this study, we tested the antitumor activity of SB743921 in breast cancer cell lines and partly elucidated its mechanisms. KSP and denticleless E3 ubiquitin-protein ligase homolog (DTL) are overexpressed in breast cancer cells compared with no-cancer tissues. Chemical inhibition of KSP by SB743921 not only reduces proliferation but also induces cell-cycle arrest and leads to apoptosis in breast cancer cells. Treatment of MCF-7 and MDA-MB-231 breast cancer cell lines with SB743921 results in decreased ability of colony formation in culture. SB743921 treatment also causes a KSP accumulation in protein level that is associated with cell arrest. Furthermore, we showed that SB743921 treatment significantly reduces the expression of bcl-2 and cell cycle-related protein DTL, and upregulates p53 and caspase-3 in breast cancer cells. Taken together, these data indicated that SB743921 can be expected to be a novel treatment agent for breast cancers. PMID- 27379934 TI - Complications Renales De L'Hypertension. AB - High blood pressure has a deleterious effect on the kidney. It significantly modifies renal handling of water and electrolytes partially, at least, as a result of haemodynamic changes in the kidney. These disorders, which are observed only under conditions of maximal stimulation, are of little interest to the clinician. Hypertension ultimately accelerates the ageing process of the kidney resulting in benign nephrosclerosis. This latter condition is not usually a cause of severe renal failure. Severe elevation of blood pressure occasionally induces malignant hypertension. This condition is characterized by necrotizing angeitis associated with subacute renal failure. Prompt and efficient hypotensive therapy may prevent or stabilize renal insufficiency. In a few cases, a return of normal renal function has been observed despite initial acute renal failure. The prognosis of malignant hypertension is determined largely by th2 degree of renal insufficien cy prevailing when hypotensive therapy is started. At first, lowering blood pressure may decrease glomerular filtration rate. In the long run, however, renal function improves. PMID- 27379935 TI - Drievoudige Antihypertensive Behandeling. AB - The systemic arterial pressure is determined by 1) the cardiac output, 2) the blood volume, and 3) the total peripheral resistance. A triple antihypertensive therapy is therefore considered which interferes primarily with these three factors using 1) beta adrenergic blocking agents, 2) a low sodium diet and diuretics, and 3) vasodilating antihypertensive drugs. The hae-modynamic changes during this therapy are described. Since cardiac output, resistance and blood volume cannot be determined routinely in all hypertensive patients, a therapeutic regimen is discussed based on the determination of 1) rate, 2) body weight and 3) arterial blood pressure. PMID- 27379936 TI - Causes D'Abandon Du Traitement Anti-Hypertenseur. AB - Two recent publications have demonstrated that, in the United States, most hypertensive patients are lost to treatment by 5 years. This high percentage of abandonment is not caused by side effects of the prescribed therapy; most patients claimed they stopped the treatment because they were not correctly informed about the nature of their disease and the way the treatment had to be carried out. The frequency of drop-out may be markedly decreased if the hypertensive patient or his family has a good understanding of the disease, and correct information about the treatment and the expected results, as well as the possible side effects. PMID- 27379937 TI - Selected Sumaries. PMID- 27379939 TI - Prediction of the length of repeat post C-section hospital stay and comparison of perinatal outcomes in patients with >=3 versus <3 previous C-section. AB - OBJECTIVE: To create a model for prediction of repeat post cesarean section (CS) length of hospital stay (LOHS) in patients undergoing repeat CS. Our other aim was to compare the perinatal outcomes in patients with >=3 versus <3 previous CS procedures. METHODS: Individual characteristics, pre-, intra- and post-operative data of 186 pregnant women who had >=3 previous CS were compared with 195 pregnant women with <3 previous CS. RESULTS: Regression analyses revealed that models can be used to predict the dependents "postpartum LOHS" and "needed units of erythrocyte suspension", both pre-operatively and intra-operatively. Patients with >=3 previous CS procedures were older, delivered earlier and had lower Apgar 1 and Apgar 5 values than patients with <3 previous CS. The rate of elective CS operations was lower in patients with >=3 previous CS. Pregnant women >=3 previous CS had significantly more severe intraperitoneal adhesion (IPA) and higher rate of bladder injury. CONCLUSIONS: Prediction models can be conducted for LOHS and other perinatal and operative parameters in patients with previous CS. Pregnancy and repeat CS, even in patients with >=3 previous CS procedures, are both safe conditions with optimal follow-up and management. PMID- 27379940 TI - Letter From the Editor: When will we ever learn? PMID- 27379941 TI - The role of microsatellite instability testing in management of colorectal cancer. PMID- 27379942 TI - The Mediterranean diet in hypercoagulable states and cancer. PMID- 27379943 TI - Highlights in breast cancer from the 2016 American Society of Clinical Oncology Annual Meeting. PMID- 27379944 TI - Management of invasive Aspergillosis in acute myelogenous leukemia. PMID- 27379945 TI - Current insights into the impact of dihydropyrimidine dehydrogenase deficiency in patients receiving treatment with 5-fluorouracil. PMID- 27379946 TI - Update on the biology and management of neuroendocrine prostate cancer. PMID- 27379947 TI - Long-term outcomes of neoadjuvant treatment of HER2-positive breast cancer. AB - Long-term outcomes for women with a diagnosis of human epidermal growth factor receptor 2 (HER2)-driven early-stage breast cancer have significantly improved since the advent of HER2-targeted therapy. Although the first studies in the early-stage setting focused on the adjuvant use of trastuzumab plus chemotherapy, clinical trials increasingly are using a neoadjuvant design to evaluate novel HER2-targeted therapies. Neoadjuvant therapy downstages locally advanced breast cancer, improves rates of breast conservation, and provides information regarding the responsiveness of a cancer to systemic therapy; in addition, studies have shown that the pathologic response to neoadjuvant therapy is correlated with event-free and overall survival. Given these advantages, multiple studies of neoadjuvant therapy, several of which have reported longer-term outcomes, have been conducted to evaluate HER2-targeted therapies. This review summarizes available data from prior and ongoing neoadjuvant trials in HER2-positive breast cancer, focusing on those studies that have reported not only pathologic response rates but also event-free, disease-free, and/or overall survival. The long-term outcomes associated with the achievement of a pathologic complete response are explored, and the comparisons of pathologic complete response rates, event-free survival, and overall survival reported for different HER2-targeted regimens are reviewed. PMID- 27379948 TI - Bruton's tyrosine kinase inhibitors in chronic lymphocytic leukemia and lymphoma. AB - The development of Bruton's tyrosine kinase (BTK) inhibitors and their introduction into clinical practice represent a major advance in the treatment of chronic lymphocytic leukemia (CLL) and other B-cell lymphomas. Although ibrutinib is the only BTK inhibitor that has been approved by the US Food and Drug Administration, several others are under investigation. Ibrutinib is currently approved for use in relapsed/refractory CLL, CLL with 17p deletion (del[17p]), relapsed or refractory mantle cell lymphoma, and Waldenstrom macroglobulinemia. Although it is clear that ibrutinib has altered treatment paradigms and outcomes in these diseases, several questions remain regarding (1) its role in frontline vs salvage therapy; (2) its use as a single agent vs in combination with biologic agents, other small molecules, or traditional chemoimmunotherapy; (3) the optimal duration of treatment; and (4) the treatment of patients who cannot tolerate or have disease resistant to ibrutinib. Because sparse clinical data are available on other BTK inhibitors, it is unclear at present whether their clinical efficacy and toxicity will differ from those of ibrutinib. PMID- 27379949 TI - In-Cell Protein Structures from 2D NMR Experiments. AB - In-cell NMR spectroscopy provides atomic resolution insights into the structural properties of proteins in cells, but it is rarely used to solve entire protein structures de novo. Here, we introduce a paramagnetic lanthanide-tag to simultaneously measure protein pseudocontact shifts (PCSs) and residual dipolar couplings (RDCs) to be used as input for structure calculation routines within the Rosetta program. We employ this approach to determine the structure of the protein G B1 domain (GB1) in intact Xenopus laevis oocytes from a single set of 2D in-cell NMR experiments. Specifically, we derive well-defined GB1 ensembles from low concentration in-cell NMR samples (~50 MUM) measured at moderate magnetic field strengths (600 MHz), thus offering an easily accessible alternative for determining intracellular protein structures. PMID- 27379950 TI - Neurophysiological Mechanisms of Auditory Information Processing in Adolescence: A Study on Sex Differences. AB - To date, little is known about sex differences in the neurophysiological correlates underlying auditory information processing. In the present study, auditory evoked potentials were evoked in typically developing male (n = 15) and female (n = 14) adolescents (13-18 years) during an auditory oddball task. Girls compared to boys displayed lower N100 and P300 amplitudes to targets. Larger N100 amplitudes in adolescent boys might indicate higher neural sensitivity to changes of incoming auditory information. The P300 findings point toward sex differences in auditory working memory and might suggest that adolescent boys might allocate more attentional resources when processing relevant auditory stimuli than adolescent girls. PMID- 27379951 TI - Validity of Treadmill-Derived Critical Speed on Predicting 5000-Meter Track Running Performance. AB - Nimmerichter, A, Novak, N, Triska, C, Prinz, B, and Breese, BC. Validity of treadmill-derived critical speed on predicting 5,000-meter track-running performance. J Strength Cond Res 31(3): 706-714, 2017-To evaluate 3 models of critical speed (CS) for the prediction of 5,000-m running performance, 16 trained athletes completed an incremental test on a treadmill to determine maximal aerobic speed (MAS) and 3 randomly ordered runs to exhaustion at the [INCREMENT]70% intensity, at 110% and 98% of MAS. Critical speed and the distance covered above CS (D') were calculated using the hyperbolic speed-time (HYP), the linear distance-time (LIN), and the linear speed inverse-time model (INV). Five thousand meter performance was determined on a 400-m running track. Individual predictions of 5,000-m running time (t = [5,000-D']/CS) and speed (s = D'/t + CS) were calculated across the 3 models in addition to multiple regression analyses. Prediction accuracy was assessed with the standard error of estimate (SEE) from linear regression analysis and the mean difference expressed in units of measurement and coefficient of variation (%). Five thousand meter running performance (speed: 4.29 +/- 0.39 m.s; time: 1,176 +/- 117 seconds) was significantly better than the predictions from all 3 models (p < 0.0001). The mean difference was 65-105 seconds (5.7-9.4%) for time and -0.22 to -0.34 m.s ( 5.0 to -7.5%) for speed. Predictions from multiple regression analyses with CS and D' as predictor variables were not significantly different from actual running performance (-1.0 to 1.1%). The SEE across all models and predictions was approximately 65 seconds or 0.20 m.s and is therefore considered as moderate. The results of this study have shown the importance of aerobic and anaerobic energy system contribution to predict 5,000-m running performance. Using estimates of CS and D' is valuable for predicting performance over race distances of 5,000 m. PMID- 27379952 TI - High School Athletes' Perceptions of the Motivational Climate in Their Off-Season Training Programs. AB - Chamberlin, JM, Fry, MD, and Iwasaki, S. High school athletes' perceptions of the motivational climate in their off-season training programs. J Strength Cond Res 31(3): 736-742, 2017-Athletes benefit tremendously from working hard in off season training (OST) because it sets them up to avoid injuries and perform their best during the season. Ironically, many athletes struggle to stay motivated to participate regularly in this training. Research has highlighted the benefits for athletes perceiving a caring and task-involving climate, where they gauge their success based on their personal effort and improvement, and perceive each member of the team is treated with mutual kindness and respect. Athletes who perceive a caring and task-involving climate on their teams are more likely to report greater adaptive motivational responses. Research has not currently examined athletes' perceptions of the climate in OST programs. The purpose of this study was to examine the relationship between athletes' perceptions of the climate in an OST program and their motivational responses. High school athletes (N = 128; 90 males 35 females; mean age = 15.3 years) participating in summer OST programs completed a survey that included measures of intrinsic motivation, commitment, their valuing OST, feeling like it is their decision to participate in OST, their perceptions that their teammates take OST seriously, and attendance. A canonical correlation revealed that athletes, who perceived a highly caring and task involving climate reported higher intrinsic motivation, value of and commitment to OST; attendance; and perceived teammates take OST seriously. Results suggest that creating a caring and task-involving climate in OST programs may help athletes optimize their motivation to participate in important strength and conditioning programs. PMID- 27379953 TI - No Dose-Response Effect of Carbohydrate Mouth Rinse Concentration on 5-km Running Performance in Recreational Athletes. AB - Clarke, ND, Thomas, JR, Kagka, M, Ramsbottom, R, and Delextrat, A. No dose response effect of carbohydrate mouth rinse concentration on 5-km running performance in recreational athletes. J Strength Cond Res 31(3): 715-720, 2017 Oral carbohydrate rinsing has been demonstrated to provide beneficial effects on exercise performance of durations of up to 1 hour, albeit predominately in a laboratory setting. The aim of the present study was to investigate the effects of different concentrations of carbohydrate solution mouth rinse on 5-km running performance. Fifteen healthy men (n = 9; mean +/- SD age; 42 +/- 10 years; height, 177.6 +/- 6.1 cm; body mass, 73.9 +/- 8.9 kg) and women (n = 6; mean +/- SD age, 43 +/- 9 years; height, 166.5 +/- 4.1 cm; body mass, 65.7 +/- 6.8 kg) performed a 5-km running time trial on a track on 4 separate occasions. Immediately before starting the time trial and then after each 1 km, subjects rinsed 25 ml of 0, 3, 6, or 12% maltodextrin for 10 seconds. Mouth rinsing with 0, 3, 6, or 12% maltodextrin did not have a significant effect on the time to complete the time trial (0%, 26:34 +/- 4:07 minutes:seconds; 3%, 27:17 +/- 4:33 minutes:seconds; 6%, 27:05 +/- 3:52 minutes:seconds; 12%, 26:47 +/- 4.31 minutes:seconds; p = 0.071; (Equation is included in full-text article.)= 0.15), heart rate (p = 0.095; (Equation is included in full-text article.)= 0.16), rating of perceived exertion (p = 0.195; (Equation is included in full-text article.)= 0.11), blood glucose (p = 0.920; (Equation is included in full-text article.)= 0.01), and blood lactate concentration (p = 0.831; (Equation is included in full-text article.)= 0.02), with only nonsignificant trivial to small differences between concentrations. Results of this study suggest that carbohydrate mouth rinsing provides no ergogenic advantage over an acaloric placebo (0%) and that there is no dose-response relationship between carbohydrate solution concentration and 5-km track running performance. PMID- 27379954 TI - Mechanical Determinants of Faster Change of Direction Speed Performance in Male Athletes. AB - Dos'Santos, T, Thomas, C, Jones, PA, and Comfort, P. Mechanical determinants of faster change of direction speed performance in male athletes. J Strength Cond Res 31(3): 696-705, 2017-Mechanical variables during change of directions, for example, braking and propulsive forces, impulses, and ground contact times (GCT) have been identified as determinants of faster change of direction speed (CODS) performance. The purpose of this study was to investigate the mechanical determinants of 180 degrees CODS performance with mechanical characteristic comparisons between faster and slower performers; while exploring the role of the penultimate foot contact (PEN) during the change of direction. Forty multidirectional male athletes performed 6 modified 505 (mod505) trials (3 left and right), and ground reaction forces were collected across the PEN and final foot contact (FINAL) during the change of direction. Pearson's correlation coefficients and coefficients of determination were used to explore the relationship between mechanical variables and mod505 completion time. Independent T-tests and Cohen's d effect sizes (ES) were conducted between faster (n = 10) and slower (n = 10) mod505 performers to explore differences in mechanical variables. Faster CODS performance was associated (p <= 0.05) with shorter GCTs (r = 0.701-0.757), greater horizontal propulsive forces (HPF) (r = -0.572 to 0.611), greater horizontal braking forces (HBF) in the PEN (r = -0.337), lower HBF ratios (r = -0.429), and lower FINAL vertical impact forces (VIF) (r = 0.449 0.559). Faster athletes demonstrated significantly (p <= 0.05, ES = 1.08-2.54) shorter FINAL GCTs, produced lower VIF, lower HBF ratios, and greater HPF in comparison to slower athletes. These findings suggest that different mechanical properties are required to produce faster CODS performance, with differences in mechanical properties observed between fast and slower performers. Furthermore, applying a greater proportion of braking force during the PEN relative to the FINAL may be advantageous for turning performance. PMID- 27379955 TI - Relationships Between Measures of Physical Fitness Change When Age-Dependent Bias is Removed in a Group of Young Male Soccer Players. AB - James, RS, Thake, CD, and Birch, SL. Relationships between measures of physical fitness change when age-dependent bias is removed in a group of young male soccer players. J Strength Cond Res 31(8): 2100-2109, 2017-Age-dependent bias is a key issue within talent identification of children, particularly when measures of physical fitness are used. Coaches in sport would benefit from a relatively straightforward method to remove age-dependent bias, enabling identification of children who are relatively high performers for their age. This study aimed to determine whether removal of age effects caused changes in the relationships between physical performance and anthropometric measures commonly used in talent identification and development systems. Sixty male soccer players, aged 11-17 years, underwent measures of anthropometry, muscular power, strength, sprint speed, and agility. Most absolute measures of performance were significantly correlated with each other, and all performance measures were significantly correlated with age. Age residuals were calculated, for all variables, to determine which players performed relatively well for their age and to investigate age-independent relationships between variables. In general, players with relatively fast sprint performance for their age were taller and had relatively high performance in jump power output and grip strength for their age (r > 0.25 and p < 0.025 in each case). Absolute sprint performance PC1 was significantly correlated with absolute agility performance PC1 (r = 0.473, p < 0.001). However, there was no significant relationship between age-independent measures of agility and any other measures. Usage of age residuals highlights performers that have relatively high physical fitness for their age. Such analyses may assist the talent identification and development processes as long as differential rates of physical development between players are also considered. PMID- 27379956 TI - Resting Heart Rate Variability Among Professional Baseball Starting Pitchers. AB - Cornell, DJ, Paxson, JL, Caplinger, RA, Seligman, JR, Davis, NA, and Ebersole, KT. Resting heart rate variability among professional baseball starting pitchers. J Strength Cond Res 31(3): 575-581, 2017-The purpose of this study was to examine the changes in resting heart rate variability (HRV) across a 5-day pitching rotation schedule among professional baseball starting pitchers. The HRV data were collected daily among 8 Single-A level professional baseball starting pitchers (mean +/- SD, age = 21.9 +/- 1.3 years; height = 185.4 +/- 3.6 cm; weight = 85.2 +/- 7.5 kg) throughout the entire baseball season with the participant quietly lying supine for 10 minutes. The HRV was quantified by calculating the natural log of the square root of the mean sum of the squared differences (lnRMSSD) during the middle 5 minutes of each R-R series data file. A split-plot repeated-measures analysis of variance was used to examine the influence of pitching rotation day on resting lnRMSSD. A statistically significant main effect of rotation day was identified (F4,706 = 3.139, p = 0.029). Follow-up pairwise analyses indicated that resting lnRMSSD on day 2 was significantly (p <= 0.05) lower than all other rotation days. In addition, a statistically significant main effect of pitcher was also identified (F7,706 = 83.388, p < 0.001). These results suggest that professional baseball starting pitchers display altered autonomic nervous system function 1 day after completing a normally scheduled start, as day 2 resting HRV was significantly lower than all other rotation days. In addition, the season average resting lnRMSSD varied among participants, implying that single-subject analysis of resting measures of HRV may be more appropriate when monitoring cumulative workload among this cohort population of athletes. PMID- 27379957 TI - Pre-Training Muscle Characteristics of Subjects Who Are Obese Determine How Well Exercise Training Will Improve Their Insulin Responsiveness. AB - Stuart, CA, Lee, ML, South, MA, Howell, MEA, Cartwright, BM, Ramsey, MW, and Stone, MH. Pre-training muscle characteristics of subjects who are obese determine how well exercise training will improve their insulin responsiveness. J Strength Cond Res 31(3): 798-808, 2017-Only half of prediabetic subjects who are obese who underwent exercise training without weight loss increased their insulin responsiveness. We hypothesized that those who improved their insulin responsiveness might have pretraining characteristics favoring a positive response to exercise training. Thirty nondiabetic subjects who were obese volunteered for 8 weeks of either strength training or endurance training. During training, subjects increased their caloric intake to prevent weight loss. Insulin responsiveness by euglycemic clamps and muscle fiber composition, and expression of muscle key biochemical pathways were quantified. Positive responders initially had 52% higher intermediate muscle fibers (fiber type IIa) with 27% lower slow twitch fibers (type I) and 23% lower expression of muscle insulin receptors. Whether after weight training or stationary bike training, positive responders' fiber type shifted away from type I and type IIa fibers to an increased proportion of type IIx fibers (fast twitch). Muscle insulin receptor expression and glucose transporter type 4 (GLUT4) expression increased in all trained subjects, but these moderate changes did not consistently translate to improvement in whole-body insulin responsiveness. Exercise training of previously sedentary subjects who are obese can result in muscle remodeling and increased expression of key elements of the insulin pathway, but in the absence of weight loss, insulin sensitivity improvement was modest and limited to about half of the participants. Our data suggest rather than responders being more fit, they may have been less fit, only catching up to the other half of subjects who are obese whose insulin responsiveness did not increase beyond their pretraining baseline. PMID- 27379958 TI - Strength-Power Performance of Visually Impaired Paralympic and Olympic Judo Athletes From the Brazilian National Team: A Comparative Study. AB - Loturco, I, Nakamura, FY, Winckler, C, Braganca, JR, da Fonseca, RA, Filho, JM, Zaccani, WA, Kobal, R, Cal Abad, CC, Kitamura, K, Pereira, LA, and Franchini, E. Strength-power performance of visually impaired paralympic and olympic judo athletes from the brazilian national team: a comparative study. J Strength Cond Res 31(3): 743-749, 2017-The aim of this study was to compare the muscle power and maximal isometric strength capacities of Olympic and visually impaired Paralympic judo athletes. Twenty-eight elite judo athletes (7 men and 7 women per group) from the permanent Brazilian National Paralympic and Olympic teams took part in this study. After a specific warm-up, the athletes performed loaded jump squat (JS), bench press (BP), and standing barbell row (SBR) exercises to determine their values of maximum mean propulsive power (MPP) in these respective exercises. The maximal isometric strength (MIS) was also determined for both upper and lower limbs, through the use of BP and half-squat (HS) exercises. Finally, the jumping ability was assessed using unloaded squat jump (SJ). The magnitude-based inference was used to compare the groups. The Olympic judo athletes presented a likely higher SJ height than the Paralympic athletes. The Olympic group presented almost certainly higher MPP in the loaded JS and in the SBR exercises and likely higher MPP in the BP exercise. Importantly, in the MIS assessments the differences between groups in the HS and BP exercises were rated as unclear. In conclusion, our results showed that both Olympic and Paralympic judo athletes present similar levels of maximal isometric strength, but muscle power performance is superior in Olympic athletes. PMID- 27379959 TI - Interday Reliability of the Reactive Strength Index and Optimal Drop Height. AB - Byrne, DJ, Browne, DT, Byrne, PJ, and Richardson, N. Interday reliability of the reactive strength index and optimal drop height. J Strength Cond Res 31(3): 721 726, 2017-The purpose of this study was to investigate the interday reliability of the reactive strength index (RSI) and optimal drop height (ODH) identification from multiple drop heights. Nineteen male trained hurling players (23.1 +/- 2.9 years, 83.1 +/- 15.5 kg, and 182.5 +/- 4.89 cm) completed 2 maximal depth jumps from 4 incremental drop heights (30, 40, 50, and 60 cm), over 2 separate testing sessions 48 hours apart. The RSI and ODH were analyzed for reliability using intraclass correlation coefficient (ICC) and coefficient of variation (CV). The RSI and ODH both demonstrated good reliability with ICC >=0.80 (0.87 and 0.81) and CV <=10% (4.2 and 2.98), respectively. The results of this study support the use of an incremental depth jump protocol to find the RSI and ODH in trained hurlers. It is recommended that the incremental depth jump protocol be used when assessing an athlete's reactive strength, as it allows a reactive strength profile, maximum RSI, and an ODH to be determined, all of which can provide vital information when determining an athletes training intensity and load. PMID- 27379960 TI - Effects of Vitamin D Supplementation on Muscle Strength in Athletes: A Systematic Review. AB - Chiang, C-m, Ismaeel, A, Griffis, RB, and Weems, S. Effects of vitamin D supplementation on muscle strength in athletes: A systematic review. J Strength Cond Res 31(2): 566-574, 2017-The purpose of this systematic review of the literature was to investigate the effects of vitamin D supplementation on muscle strength in athletes. A computerized literature search of 3 databases (PubMed, MEDLINE, and Scopus) was performed. Included in the review were randomized controlled trials (RCTs), published in English, which measured serum vitamin D concentrations and muscle strength in healthy, athletic participants aged 18-45 years. Quality was assessed using the PEDro scale. Five RCTs and 1 controlled trial were identified, and quality assessment showed 5 trials were of "excellent quality" and 1 was of "good quality." Trials lasted from 4 weeks to 6 months and dosages ranged from 600 to 5,000 International Units (IU) per day. Vitamin D2 was found to be ineffective at impacting muscle strength in both studies wherein it was administered. In contrast, vitamin D3 was shown to have a positive impact on muscle strength. In 2 studies, strength outcome measures were significantly improved after supplementation (p <= 0.05). In the other 2 studies administering vitamin D3, there were trends for improved muscle strength. Specifically, improvements in strength ranged from 1.37 to 18.75%. Additional studies are needed to confirm these associations. PMID- 27379961 TI - A Comparison of Mixed-Method Cooling Interventions on Preloaded Running Performance in the Heat. AB - Stevens, CJ, Bennett, KJM, Sculley, DV, Callister, R, Taylor, L, and Dascombe, BJ. A comparison of mixed-method cooling interventions on preloaded running performance in the heat. J Strength Cond Res 31(3): 620-629, 2017-The purpose of this investigation was to assess the effect of combining practical methods to cool the body on endurance running performance and physiology in the heat. Eleven trained male runners completed 4 randomized, preloaded running time trials (20 minutes at 70% V[Combining Dot Above]O2max and a 3 km time trial) on a nonmotorized treadmill in the heat (33 degrees C). Trials consisted of precooling by combined cold-water immersion and ice slurry ingestion (PRE), midcooling by combined facial water spray and menthol mouth rinse (MID), a combination of all methods (ALL), and control (CON). Performance time was significantly faster in MID (13.7 +/- 1.2 minutes; p < 0.01) and ALL (13.7 +/- 1.4 minutes; p = 0.04) but not PRE (13.9 +/- 1.4 minutes; p = 0.24) when compared with CON (14.2 +/- 1.2 minutes). Precooling significantly reduced rectal temperature (initially by 0.5 +/- 0.2 degrees C), mean skin temperature, heart rate and sweat rate, and increased iEMG activity, whereas midcooling significantly increased expired air volume and respiratory exchange ratio compared with control. Significant decreases in forehead temperature, thermal sensation, and postexercise blood prolactin concentration were observed in all conditions compared with control. Performance was improved with midcooling, whereas precooling had little or no influence. Midcooling may have improved performance through an attenuated inhibitory psychophysiological and endocrine response to the heat. PMID- 27379962 TI - Association Between Anaerobic Metabolic Demands During Simulated Brazilian Jiu Jitsu Combat and Specific Jiu-Jitsu Anaerobic Performance Test. AB - Villar, R, Gillis, J, Santana, G, Pinheiro, DS, and Almeida, ALRA. Association between anaerobic metabolic demands during simulated Brazilian jiu-jitsu combat and specific jiu-jitsu anaerobic performance test. J Strength Cond Res 32(2): 432 440, 2018-The aims of this study were to design a specific Jiu-Jitsu anaerobic performance test (JJAPT) and investigate the relationship between blood lactate ([La]), heart rate (HR), and rating of perceived exertion (RPE) during simulated Brazilian Jiu-Jitsu combat (SBJJC) and JJAPT. Nine male elite Brazilian medium heavy weight athletes performed a 10-minute SBJJC and JJAPT that required performance of a common BJJ technique for 5 consecutive bouts of 1-minute with 45 second rest between bouts. [La] was measured by a lactate analyzer, HR by an HR monitor, and RPE using Borg's scale, and the number of repetitions of butterfly lifts (NBL) was recorded. During JJAPT, NBL decreased in the fourth and fifth bouts (p <= 0.05) with increases in [La], HR, and RPE (p <= 0.05), indicating that the JJAPT measured anaerobic performance. [La] during SBJJC was not different than [La] at the third and fourth bouts, but was significantly different than the fifth bout (p <= 0.05). [La] showed strong correlation between SBJJC and JJAPT for the third (r = 0.80, p <= 0.05), fourth (r = 0.83, p <= 0.05), and fifth (r = 0.82, p <= 0.05) bouts, but not between the HR and RPE. The JJAPT with 4 bouts presented the best combination of stimulus and highest correlation with SBJJC, supporting its use to assess anaerobic performance of BJJ athletes. These data will aid coaches and athletes to better understand the demands of their sport and may help to monitor adaptation in sport-specific performance across periodized training plans. PMID- 27379963 TI - Individual Response to Different Forms of Resistance Training in School-Aged Boys. AB - Radnor, JM, Lloyd, RS, and Oliver, JL. Individual response to different forms of resistance training in school-aged boys. J Strength Cond Res 31(3): 787-797, 2017 The aim of this study was to examine individual responses to different forms of resistance training on measures of jumping and sprinting performance in school aged boys. Eighty boys were categorized into 2 maturity groups (pre- or post-peak height velocity [PHV]) and randomly assigned to a plyometric training, resistance training, combined training, or control group. Intervention groups participated in training twice weekly for 6 weeks, with measures of acceleration, maximal running velocity, squat jump height, and reactive strength index (RSI) collected preintervention and postintervention. In the pre-PHV cohort, plyometric training and combined training resulted in significantly more positive responders than the other 2 groups in both sprint variables (standardized residual values >1.96). In the post-PHV cohort, significantly more positive responders for acceleration and squat jump height resulted from traditional strength training and combined training groups, compared with other groups. Conversely, plyometric training and combined training resulted in a significantly greater number of positive responders than the other 2 groups for maximal velocity and RSI. Control participants rarely demonstrated meaningful changes in performance over the 6 week period. Irrespective of maturation, it would seem that combined training provides the greatest opportunity for most individuals to make short-term improvements in jump and sprint performance. Taking maturation into account, our data show that a plyometric training stimulus is important for individuals in the pre-PHV stage of development, whether as a stand-alone method or in combination with traditional strength training, when attempting to improve jumping and sprinting ability. However, individuals in the post-PHV stage require a more specific training stimulus depending on the performance variable that is being targeted for improvement. PMID- 27379964 TI - Changes in Rugby League Tackling Ability During a Competitive Season: The Relationship With Strength and Power Qualities. AB - Speranza, MJA, Gabbett, TJ, Greene, DA, Johnston, RD, and Sheppard, JM. Changes in rugby league tackling ability during a competitive season: the relationship with strength and power qualities. J Strength Cond Res 31(12): 3311-3318, 2017 This study examined the relationship between changes in tackling ability, and muscular strength and power during a semiprofessional rugby league competitive season. Twelve semiprofessional rugby league players (mean +/- SD age, 23.3 +/- 2.0 years) underwent tests of upper- and lower-body strength and power during the preseason period. Tackling ability was tested using video analysis of a standardized one-on-one tackling drill. Players repeated these tests after round 15 of a 25-match competitive season. Changes in 1 repetition maximum (1RM) squat (rs = 0.70; p < 0.02) and squat relative to body mass (rs = 0.73; p < 0.01) were significantly related to changes in tackling ability. Players with the greatest improvements in tackling ability (i.e., "responders") retained 1RM squat (effect size, ES = 0.85, p = 0.09) and squat relative to body mass (ES = 0.82, p = 0.15) to a greater extent than the "nonresponders." The results of this study suggest that players who retained lower-body strength were able to improve tackling ability during the competitive season, whereas reductions in lower-body strength were associated with decrements in tackling ability. This study highlights the importance of the development and maintenance of lower-body muscular strength for effective tackling performance throughout the rugby league season. PMID- 27379965 TI - Neuromuscular Activity and Muscular Oxygenation Through Different Movement Cadences During In-water and On-land Knee Extension Exercise. AB - Chien, K-Y, Kan, N-W, Liao, Y-H, Lin, Y-L, Lin, C-L, and Chen, W-C. Neuromuscular activity and muscular oxygenation through different movement cadences during in water and on-land knee extension exercise. J Strength Cond Res 31(3): 750-757, 2017-The purpose of this study was to determine the influence of various knee extension exercise cadences on neuromuscular activation and hemodynamic properties of the quadriceps muscle in water and on land. Seventeen young women participated in this study, and the subjects were randomly allocated to perform loaded knee extension exercises in water and on land at 4 different cadences of 30, 50, 70, and 90 b.min. Heart rate (HR), blood flow (BF), total saturation index (TSI) of oxygen, electromyography (EMG) for the extent of muscular activity, and rate of perceived exertion (RPE) were measured. Response values of HR, BF, TSI, and RPE at each cadence were obtained by subtracting the resting values from the indicator values measured at the respective cadences. We observed that BF, EMG, and RPE in water at 90 b.min were comparable with those on land. The HR and TSI changes were higher in water compared with on land (p = 0.004 and p = 0.013, respectively). In conclusion, we demonstrate that the neuromuscular activity when performing knee extension exercises at 90 b.min in water was comparable with that on land. However, exercising in water at the same cadence evoked higher TSI responses and greater cardiovascular challenges. A knee extension exercise at 90 b.min is the recommended operating speed of rehabilitation in water. PMID- 27379966 TI - Developing a Digital Medicine System in Psychiatry: Ingestion Detection Rate and Latency Period. AB - BACKGROUND: A digital medicine system (DMS) has been developed to measure and report adherence to an atypical antipsychotic, aripiprazole, in psychiatric patients. The DMS consists of 3 components: ingestible sensor embedded in a medication tablet, wearable sensor, and secure mobile and cloud-based applications. An umbrella study protocol was designed to rapidly assess the technical performance and safety of the DMS in multiple substudies to guide the technology development. METHODS: Two sequential substudies enrolled 30 and 29 healthy volunteers between March-April 2014 and February-March 2015, respectively, to assess detection accuracy of the ingestible sensor by the DMS and the latency period between ingestion and detection of the ingestion by the wearable sensor or the cloud-based server. RESULTS: The first substudy identified areas for improvement using early versions of the wearable sensor and the mobile application. The second substudy tested updated versions of the components and showed an overall ingestion detection rate of 96.6%. Mean latency times for the signal transmission were 1.1-1.3 minutes (from ingestion to the wearable sensor detection) and 6.2-10.3 minutes (from the wearable sensor detection to the server detection). Half of transmissions were completed in < 2 minutes, and ~90% of ingestions were registered by the smartphone within 30 minutes of ingestion. No serious adverse events, discontinuations, or clinically significant laboratory/vital signs findings were reported. CONCLUSIONS: The DMS implementing modified versions of the smartphone application and the wearable sensor has the technical capability to detect and report tablet ingestion with high accuracy and acceptable latency time. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02091882. PMID- 27379968 TI - Interstitial pneumonia with autoimmune features: a critical appraisal of the new definition. AB - PURPOSE OF REVIEW: We review the newly formulated and published research classification criteria for interstitial pneumonia with autoimmune features and appraise these criteria in light of findings from recent investigations. RECENT FINDINGS: Previous studies demonstrated that interstitial pneumonia may be caused by an autoimmune process with a variety of names and criteria utilized for this entity. To standardize terminology and provide a definition for future research, a multidisciplinary task force formulated criteria by which patients with interstitial lung disease and autoimmune features might be recognized. The interstitial pneumonia with autoimmune features criteria require the presence of an interstitial pneumonia on chest imaging or surgical lung biopsy, exclusion of an alternate cause, the absence of a defined connective tissue disease and at least one feature suggestive of autoimmunity from at least two of three domains: clinical with specific extra-thoracic features, serologic with positive autoantibodies and morphologic as demonstrated by chest imaging, histopathology, or multicompartment involvement. Although recent studies provide insight into features of significance, these criteria have not undergone formal validation. SUMMARY: A uniform name and set of research criteria for interstitial pneumonia with autoimmune features may identify patients with treatment responsive interstitial lung disease and an improved prognosis. These criteria require validation before they can be applied in the clinical setting. PMID- 27379967 TI - From granuloma to fibrosis: sarcoidosis associated pulmonary fibrosis. AB - PURPOSE OF REVIEW: Up to twenty percent of patients with sarcoidosis develop pulmonary fibrosis, transforming an often benign disease into a highly morbid and potentially fatal one. We highlight the fibrotic pulmonary sarcoidosis phenotype as an area of intense clinical and translational investigation, review recent developments in treatment, and provide a roadmap for future research in sarcoidosis associated pulmonary fibrosis. RECENT FINDINGS: Granulomatous inflammation in a lymphatic distribution is the hallmark finding of pulmonary sarcoidosis and the nidus for fibrosis. Recent research demonstrates that fibrotic sarcoidosis begins in the setting of persistent, uncontrolled inflammation, and is aided by pro-fibrotic genetic features and immune responses. Comparison to other fibrotic lung diseases also reveals key features that inform our understanding of common pathways in fibrosis. SUMMARY: Understanding the mechanisms of fibrotic transformation in sarcoidosis enhances clinical care and facilitates development of novel therapeutic options. The impact of these findings in fibrotic sarcoidosis may be amplified through application to other interstitial lung diseases marked by inflammatory to fibrotic transformation. Important aspects of clinical management of fibrotic sarcoidosis include surveillance for co-morbidities, such as pulmonary hypertension, airway disease, and infection, and assessment for pulmonary disease activity that may benefit from immunosuppression. PMID- 27379969 TI - T-cell immunology in sarcoidosis: Disruption of a delicate balance between helper and regulatory T-cells. AB - PURPOSE OF REVIEW: Although the aetiology of sarcoidosis is not yet completely understood, immunological changes within the T-cell compartment are characteristic for an exaggerated antigen-driven immune response. In this review, we describe the most recent findings on T-cell subset responses and regulation in sarcoidosis. We discuss how future immunological research can advance the field to unravel pathobiological mechanisms of this intriguingly complex disease. RECENT FINDINGS: Research into the field of T-cell plasticity has recently challenged the long-held T helper type 1 (Th1) paradigm in sarcoidosis and striking parallels with autoimmune disorders and common variable immunodeficiency were recognized. For instance, it was demonstrated that Th17.1-cells rather than Th1-cells are responsible for the exaggerated IFN-gamma production in pulmonary sarcoidosis. Furthermore, impaired regulatory T-cell function and alterations within the expression of co-inhibitory receptors that control T-cell responses, such as PD-1, CTLA-4 and BTNL2, raise new questions regarding T-cell regulation in pulmonary sarcoidosis. SUMMARY: It becomes increasingly clear that Th17(.1) cells and regulatory T-cells are key players in sarcoidosis T-cell immunology. New findings on plasticity and co-inhibitory receptor expression by these subsets help build a more comprehensive model for T-cell regulation in sarcoidosis and will finally shed light on the potential of new treatment modalities. PMID- 27379970 TI - Is COPD a Risk Factor for Hip Fracture? AB - This study aimed to describe trends in the incidence of hip fracture hospitalizations, use of surgical procedures, and hospital outcomes among elderly patients with and without chronic obstructive pulmonary disease (COPD) in Spain (2004-2013). We selected all patients with a discharge primary diagnosis of hip fracture using the Spanish national hospital discharge database. Discharges were grouped by COPD status. From 2004 to 2013, 432,760 discharges with hip fracture were identified (6.9% suffered COPD). Incidence among COPD men increased by 2.63% per year from 2004 to 2013. There were no significant changes in tendency in the incidence among women with COPD during the study period. COPD women have almost three times higher incidence than COPD men. Incidences and hospital complications were higher among patients with COPD beside sex. The proportion of patients who underwent internal fixation increased for all groups of patients and the open reduction decreased. After multivariate analysis, in-hospital mortality (IHM) has improved over the study period for all patients. Suffering COPD was associated with higher IHM in men (odds ratio 1.45; 95% confidence interval 1.33-1.58) than women. In conclusion, hip fracture incidence is higher in subjects with than without COPD and is much higher among women than men. In COPD patients, incidence rates increased significantly in men from 2004 to 2013, but not in women. For all groups, the use of internal fixation has increased overtime and open reduction, IHM, and length of hospital stay have decreased from 2004 to 2013. PMID- 27379971 TI - Impaired cellular energy metabolism contributes to bluetongue-virus-induced autophagy. AB - Bluetongue virus (BTV) has been found to trigger autophagy to favor its replication, but the underlying mechanisms have not been clarified. Here, we show that cellular energy metabolism is involved in BTV-induced autophagy. Cellular ATP synthesis was impaired by BTV1 infection, causing metabolic stress, which was responsible for activation of autophagy, since the conversion of LC3 and aggregation of GFP-LC3 (autophagy markers) were suppressed when infection-caused energy depletion was reversed via MP (metabolic substrate) treatment. The reduced virus yields with MP further supported this view. Overall, our findings suggest that BTV1-induced disruption of cellular energy metabolism contributes to autophagy, and this provides new insights into BTV-host interactions. PMID- 27379972 TI - Adenomyosis: a systematic review of medical treatment. AB - Adenomyosis is a heterogeneous gynaecologic condition with a range of clinical presentations, the most common being heavy menstrual bleeding and dysmenorrhoea; however, patients can also be asymptomatic. Several studies support the theory that adenomyosis results from invasion of the endometrium into the myometrium, causing alterations in the junctional zone. These changes are commonly seen on imaging studies, such as transvaginal ultrasound and magnetic resonance imaging. The aim of this review is to discuss the medical approach to the management of adenomyosis symptoms, including pain and abnormal uterine bleeding. The standard treatment of adenomyosis is hysterectomy, but there is no medical therapy to treat the symptoms of adenomyosis while still allowing patients to conceive. Medical therapies using suppressive hormonal treatments, such as continuous use of oral contraceptive pills, high-dose progestins, selective oestrogen receptor modulators, selective progesterone receptor modulators, the levonorgestrel releasing intrauterine device, aromatase inhibitors, danazol, and gonadotrophin receptor hormone agonists can temporarily induce regression of adenomyosis and improve the symptoms. PMID- 27379973 TI - Predictive factors of mortality in pediatric patients with acute renal injury associated with sepsis. AB - OBJECTIVE: To evaluate the prognosis factors of children with sepsis and acute kidney injury. METHODS: This was a retrospective study of children with sepsis and acute kidney injury that were admitted to the pediatric intensive care unit (PICU) of a tertiary hospital. A multivariate analysis was performed to compare risk factors for mortality. RESULTS: Seventy-seven children (47 males) were retrospectively studied, median age of 4 months. Mean length of hospital stay was 7.33+/-0.16 days, 68.9% of patients received mechanical ventilation, 25.9% had oligo-anuria, and peritoneal dialysis was performed in 42.8%. The pRIFLE criteria were: injury (5.2%) and failure (94.8%), and the staging system criteria were: stage 1 (14.3%), stage 2 (29.9%), and stage 3 (55.8%). The mortality rate was 33.7%. In the multivariate analysis, the risk factors for mortality were PICU length of stay (OR=0.615, SE=0.1377, 95% CI=0.469-0.805, p=0.0004); invasive mechanical ventilation (OR=14.599, SE=1.1178, 95% CI=1.673-133.7564, p=0.0155); need for dialysis (OR=9.714, SE=0.8088, 95% CI=1.990-47.410, p=0.0049), and hypoalbuminemia (OR=10.484, SE=1.1147, 95% CI=1.179-93.200, p=0.035). CONCLUSIONS: The risk factors for mortality in children with acute kidney injury were associated with sepsis severity. PMID- 27379974 TI - Two-staged application of PRP in arthroscopic rotator cuff repair: a matched-pair analysis. AB - INTRODUCTION: Failure rates after arthroscopic rotator cuff repair remain high. Platelet-rich plasma has gained interest as a potential biological augmentation to enhance bone-tendon healing. The purpose of this study is to evaluate the clinical and structural outcomes of repeated PRP application on rotator cuff repair. MATERIALS AND METHODS: Thirty-six patients underwent arthroscopic reconstruction, using knotless anchor double-row repair. Eighteen patients [10 female, 8 male; 61.2 (+/-9.2) years] received two applications of PRP-directly subsequent to the repair and 7 days postoperatively. Eighteen patients [11 male, 7 female; 61.4 (+/-6.5) years] who solely received the same technique of rotator cuff repair were matched for age. The subjective shoulder value, WORC, and the Constant-Murley score were used for clinical evaluation. MRI was performed for tendon integrity, and cuff appearances were graded according to the Sugaya classification. RESULTS: We prospectively evaluated the PRP group with a minimum follow-up of 24 months. Clinical results did not show significantly differences in comparison to patients with isolated rotator cuff repair concerning CS (79 +/- 13 vs. 77 +/- 13; P = 0.6), SSV (90 +/- 14 vs. 88 +/- 16; P = 0.5) or WORC Score (90 +/- 18 vs. 86 +/- 20; P = 0.2). At the final follow-up, MRI showed retears in 11 % of the PRP and in 28 % of the control group (P = 0.4). CONCLUSIONS: Knotless anchor double-row repair shows good to excellent clinical results with an acceptable retear rate. Additional two-staged PRP application failed to significantly improve clinical parameters. Even though there was a trend for lower retear rates in the PRP group, it did not achieve statistical difference. LEVEL OF EVIDENCE: Level III, Retrospective comparative study. PMID- 27379976 TI - The English word disgust has no exact translation in Hindi or Malayalam. AB - Do different languages have a translation for the English word disgust that labels the same underlying concept? If not, the English word might label a culture-specific concept. Four studies (Ns = 93, 90, 180, 960) compared disgust to its common translation in Hindi (an Indo-European language) and in Malayalam (a Dravidian language) by examining two components of the concept thought of as a script: causal antecedent and facial expression. The English word was used to refer to reactions to both unclean substances and moral violations; Hindi and Malayalam translations referred mainly to moral violations. Speakers of all three languages associated different facial expressions to unclean substances and moral violations. Words for disgust in the three languages failed a test of translation equivalence (a correlation of .80 or above across emotional facial expressions). PMID- 27379975 TI - The cortical irregularity in the transition zone of the radial head and neck: a reliable radiographic sign of an occult radial head fracture. AB - PURPOSE: Exclusion or detection of non-displaced radial head fractures can be difficult in radiographs, because they might lack conclusive radiographic signs, such as fracture lines or distracted articular fragments. Based on the typical injury mechanism of a radial head fracture, causing the head to hit the capitulum and leading to a depression of the anterolateral border of the radial head, we hypothesized that even slight cortical irregularities in the transition zone of the radial neck and head result from that depression and may be a reliable radiographic sign of an underlying radial head fracture. Secondarily, we tested the null hypothesis that the lack of cortical irregularities is sufficient to exclude a fracture of the radial head. METHODS: 84 patients with sets of anteroposterior and lateral radiographs of the elbow were identified from the database of a level 1 trauma center and divided into 2 groups. Group A was formed out of 42 patients with non-displaced radial head fractures, group B out of 42 patients without a history of previous elbow trauma, whose medical history also contained radiographic images. After the radial head was blackened, the transition zone of the radial neck and head was assessed by two attending orthopedic surgeons for presence of a cortical irregularity. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cortical irregularity were calculated for the assessment of radial head fractures. The kappa measure of agreement was utilized to evaluate interrater agreement. RESULTS: The specificity was 87.80 and 97.56 %, respectively, its sensitivity 86.04 and 75.61 %. A high NPV (85.71 %; 80.00 %) and PPV (96.88 %; 88.10 %.) were observed. The interrater agreement for the proposed diagnostic method was high, with a Cohen kappa score of 0.737 (p < 0.001). CONCLUSIONS: A cortical irregularity in the transition zone of the radial neck and head seems to be a reliable radiographic sign of an underlying radial head fracture. The absence of the cortical irregularity can be used to correctly identify a non fractured radial head. PMID- 27379977 TI - Mutation in the Human HPRT1 Gene and the Lesch-Nyhan Syndrome. AB - Lesch-Nyhan syndrome (LNS) is a rare X-linked inherited neurogenetic disorder of purine metabolism in which the enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. The authors report a novel mutation which led to HGprt-related neurological dysfunction (HND) in two brothers from the same family with a missense mutation in exon 6 of the coding region of the HPRT1 gene: c.437T>C, p.L146S. Molecular diagnosis discloses the genetic heterogeneity of the HPRT1 gene responsible for HGprt deficiency. It allows fast, accurate carrier detection and genetic counseling. PMID- 27379978 TI - 4-Oxo-1,4-dihydroquinoline-3-carboxamide Derivatives as New Axl Kinase Inhibitors. AB - Axl is a new potential target for anticancer drug discovery. A series of 4-oxo 1,4-dihydroquinoline-3-carboxamides were designed and synthesized as highly potent Axl kinase inhibitors. One of the most promising compounds, 9im, tightly bound with Axl protein and potently inhibited its kinase function with a Kd value of 2.7 nM and an IC50 value of 4.0 nM, respectively, while was obviously less potent against most of the 403 wild-type kinases evaluated at a relatively high concentration. The compound dose-dependently inhibited the TGF-beta1-induced epithelial-mesenchymal transition (EMT) and suppressed the migration and invasion of MDA-MB-231 breast cancer cells. In addition, 9im also demonstrated reasonable pharmacokinetics properties in rats and exhibited in vivo therapeutic effect on hepatic metastasis in a xenograft model of highly metastatic 4T1 murine breast cancer cells. Compound 9im may serve as a lead compound for new anticancer drug discovery and a valuable research probe for further biological investigation on Axl. PMID- 27379979 TI - Implications of Predictive Low-Glucose Management System in Hybrid of Full Closed Loop System. PMID- 27379980 TI - Increasing toxicity of enrofloxacin over four generations of Daphnia magna. AB - The effects of both continuous and alternate exposure to 2mgL(-1) of enrofloxacin (EFX) on survival, growth and reproduction were evaluated over four generations of Daphnia magna. Mortality increased, reaching 100% in most groups by the end of the third generation. Growth inhibition was detected in only one group of the fourth generation. Reproduction inhibition was >50% in all groups and, in second and third generations, groups transferred to pure medium showed a greater inhibition of reproduction than those exposed to EFX. To verify whether the effects observed in these groups could be explained by the perinatal exposure to the antibacterial, a reproduction test with daphnids obtained from in vitro exposed D. magna embryos was also carried out. Perinatal exposure to EFX seemed to act as an 'all-or-nothing' toxicity effect as 31.4% of embryos died, but the surviving daphnids did not show any inhibition of reproduction activity. However, the embryonic mortality may at least partially justify the inhibition of reproduction observed in exposed groups along the multigenerational test. Concluding, the multigenerational test with D. magna did show disruption to a population that cannot be evidenced by the official tests. The increasing deterioration across generations might be inferred as the consequence of heritable alterations. Whilst the concentration tested was higher than those usually detected in the natural environment, the increasing toxicity of EFX across generations and the possible additive toxicity of fluoroquinolone mixtures, prevent harm to crustacean populations by effects in the real context from being completely ruled out. PMID- 27379981 TI - Konstantin N. Mikhelson: Ion-selective electrodes. PMID- 27379982 TI - FGFR2 overexpression predicts survival outcome in patients with metastatic papillary renal cell carcinoma. AB - BACKGROUND: Up to date, there are no data about FGFR2 expression and its predictive role in papillary RCC (pRCC) patients. The aim of the present study was to test FGFR2 expression and mutations for association with survival outcome in patients with pRCC. METHODS: Specimens of removed primary tumors from 214 untreated metastatic pRCC patients were evaluated by immunohistochemistry with FGFR2 antibody. FGFR2 mutations were assessed by PCR and direct sequencing, with DNA obtained from 62 paraffin-embedded pRCC samples. FGFR2 expression was tested for associations with progression-free survival (PFS), overall survival (OS) and best objective response. RESULTS: Expression of FGFR2 was observed in 23 % (49/214) of primary pRCC, mostly in cytoplasm of tumor cells. Expression of FGFR2 was significant lower in normal tissue of kidney (1 %, P = 0.001). FGFR2 S252W mutation was found in one patient (1.6 %), and no N549K mutation was detected. FGFR2 expression was strongly associated with a number of metastatic sites, type 2 of pRCC, lower nucleolar grade (P < 0.001). FGFR2-positive patients had significantly shorter OS and PFS (P < 0.05). On multivariate analysis, FGFR2 expression, MSKCC risk group and type of pRCC were found to be independent predictors of survival. CONCLUSIONS: In this study, we described immunohistochemical expression of FGFR2 in a large series of pRCC specimens. FGFR2 expression was found to be prognostic factor for survival in patients with metastatic pRCC. FGFR2 mutations are rare across papillary types of RCC. PMID- 27379983 TI - Phonon-Assisted Population Inversion in Lanthanide-Doped Upconversion Ba2 LaF7 Nanocrystals in Glass-Ceramics. AB - The effective population inversion of 2 H11/2 from 4 S3/2 state of Er3+ ions can be achieved through the annihilation of phonons; random lasing action from BLF films embedded with Yb3+ /Er3+ codoped BLF nanocrystals is demonstrated and high ambient temperature (>433 K) operation lasers with a very low excitation threshold (<530 nJ cm-2 ) are realized. PMID- 27379984 TI - In vivo use of the CYP inhibitor 1-aminobenzotriazole to increase long-term exposure in mice. AB - 1-Aminobenzotriazole (ABT) is a well-known in vivo nonspecific inhibitor of cytochrome P450 (CYP) enzymes. An effective dosing regimen of ABT for a multiple administration study is needed to conduct pharmacological studies for proof-of concept, although it has been established for single-administration study, to characterize the pharmacokinetics of drug candidates. This study demonstrated a suitable dosing vehicle of ABT for continuous administration and increased exposure to antipyrine, which is a nonspecific probe of CYP, using ABT for a long period in mice. The dosing vehicle of ABT was 0.5% (w/v) hydroxypropyl methylcellulose and 0.5% (v/v) Tween 80 in N,N-dimethylacetamide/20% hydroxypropyl-beta-cyclodextrin aqueous solution (2:8, v/v) based on the duration of apparent solubility. After implantation of an ALZET osmotic pump with ABT, the plasma concentrations of ABT were maintained at more than 4.1 MUg/ml over 336 h. Compared with the vehicle group, the CLtot of antipyrine with ABT decreased to approximately one-fourth, and the BA of antipyrine with ABT increased up to 3 fold. In addition, the enhancement of exposure of antipyrine by ABT was maintained over the 336 h. The body weight, food consumption and hematological parameters of mice did not change with ABT administration for 16 days. These findings demonstrated that pretreatment of ABT can increase long-term exposure using continuous administration with the ALZET osmotic pump in mice with no overt toxicity. It is concluded that the in vivo use of 1-aminobenzotriazole can be applied to pharmacological studies for proof-of-concept, thus contributing to the selection of drug candidates at an early drug discovery stage. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27379985 TI - Do Parents and Overweight, Treatment-Seeking Youth Provide Similar Ratings of Youths' Psychosocial Functioning and Fatigue? AB - Patterns of agreement between parent and child ratings of psychosocial functioning and fatigue in children with obesity were examined. Analyses demonstrated moderate agreement for social anxiety in elementary children and small agreement for social anxiety in adolescents. Results of analyses of overall quality of life revealed small agreement in children under the age of 8, large agreement in children ages 8-12, and moderate agreement in adolescents ages 13 18. Overall ratings of fatigue demonstrated moderate agreement both in elementary children and in adolescents. A meaningful relationship was found between each factor measured by a parent and a child. Patterns which were unexpected given the existing literature were found; possible hypotheses explaining these patterns are presented; and the need for further research is highlighted. PMID- 27379986 TI - Quantitative Analysis of [18F]FMISO PET for Tumor Hypoxia: Correlation of Modeling Results with Immunohistochemistry. AB - PURPOSE: Quantitative evaluation of tumor hypoxia based on H-1-(3-[18F]fluoro-2 hydroxypropyl)-2-nitroimidazole ([18F]FMISO) positron emission tomography (PET) can deliver important information for treatment planning in radiotherapy. However, the merits and limitations of different analysis methods in revealing the underlying physiological feature are not clear. This study aimed to assess these quantitative analysis methods with the support of immunohistological data. PROCEDURES: Sixteen nude mice bearing xenografted human squamous cell carcinomas (FaDu or CAL-33) were scanned using 2-h dynamic [18F]FMISO PET. Tumors were resected and sliced, and the hypoxia marker pimonidazole was immunostained followed by H&E staining. The pimonidazole signal was segmented using a k-means clustering algorithm, and the hypoxic fraction (HF) was calculated as the hypoxic area/viable tumor-tissue-area ratio pooled over three tissue slices from the apical, center, and basal layers. PET images were analyzed using various methods including static analysis [standard uptake value (SUV), tumor-to-blood ratio (T/B), tumor-to-muscle ratio (T/M)] and kinetic modeling (Casciari alphak A , irreversible and reversible two-tissue compartment k 3, Thorwarth w A k 3, Patlak K i , Logan V d , Cho K), and correlated with HF. RESULTS: No significant correlation was found for static analysis. A significant correlation between k 3 of the irreversible two-tissue compartment model and HF was observed (r = 0.61, p = 0.01). The correlation between HF and alphak A of the Casciari model could be improved through reducing local minima by testing more sets of initial values (r = 0.59, p = 0.02) or by reducing the model complexity by fixing three parameters (r = 0.63, p = 0.0008). CONCLUSIONS: With support of immunohistochemistry data, this study shows that various analysis methods for [18F]FMISO PET perform differently for assessment of tumor hypoxia. A better fitting quality does not necessarily mean a higher physiological correlation. Hypoxia PET analysis needs to consider both the mathematical stability and physiological fidelity. Based on the results of this study, preference should be given to the irreversible two tissue compartment model as well as the Casciari model with reduced parameters. PMID- 27379987 TI - Fluorescent Affibody Molecule Administered In Vivo at a Microdose Level Labels EGFR Expressing Glioma Tumor Regions. AB - PURPOSE: Fluorescence guidance in surgical oncology provides the potential to realize enhanced molecular tumor contrast with dedicated targeted tracers, potentially with a microdose injection level. For most glioma tumors, the blood brain barrier is compromised allowing some exogenous drug/molecule delivery and accumulation for imaging. The aberrant overexpression and/or activation of epidermal growth factor receptor (EGFR) is associated with many types of cancers, including glioblastoma, and so the use of a near-infrared (NIR) fluorescent molecule targeted to the EGFR receptor provides the potential for improving tumor contrast during surgery. Fluorescently labeled affibody molecule (ABY-029) has high EGFR affinity and high potential specificity with reasonably fast plasma clearance. In this study, ABY-29 was evaluated in glioma versus normal brain uptake from intravenous injection at a range of doses, down to a microdose injection level. PROCEDURE: Nude rats were inoculated with the U251 human glioma cell line in the brain. Tumors were allowed to grow for 3-4 weeks. ABY-029 fluorescence ex vivo imaging of brain slices was acquired at different time points (1-48 h) and varying injection doses from 25 to 122 MUg/kg (from human protein microdose equivalent to five times microdose levels). RESULTS: The tumor was most clearly visualized at 1-h post-injection with 8- to 16-fold average contrast relative to normal brain. However, the tumor still could be identified after 48 h. In all cases, the ABY-029 fluorescence appeared to localize preferentially in EGFR-positive regions. Increasing the injected dose from a microdose level to five times, a microdose level increased the signal by 10-fold, and the contrast was from 8 to 16, showing that there was value in doses slightly higher than the microdose restriction. Normal tissue uptake was found to be affected by the tumor size, indicating that edema was a likely factor affecting the expected tumor to normal tissue contrast. CONCLUSION: These results suggest that the NIR-labeled affibody molecules provide an excellent potential to increase surgical visualization of EGFR-positive tumor regions. PMID- 27379988 TI - Photoresponse of a Single Y-Junction Carbon Nanotube. AB - We report investigation of optical response in a single strand of a branched carbon nanotube (CNT), a Y-junction CNT composed of multiwalled CNTs. The experiment was performed by connecting a pair of branches while grounding the remaining one. Of the three branch combinations, only one combination is optically active which also shows a nonlinear semiconductor-like I-V curve, while the other two branch combinations are optically inactive and show linear ohmic I V curves. The photoresponse includes a zero-bias photocurrent from the active branch combination. Responsivity of ~1.6 mA/W has been observed from a single Y CNT at a moderate bias of 150 mV with an illumination of wavelength 488 nm. The photoresponse experiment allows us to understand the nature of internal connections in the Y-CNT. Analysis of data locates the region of photoactivity at the junction of only two branches and only the combination of these two branches (and not individual branches) exhibits photoresponse upon illumination. A model calculation based on back-to-back Schottky-type junctions at the branch connection explains the I-V data in the dark and shows that under illumination the barriers at the contacts become lowered due to the presence of photogenerated carriers. PMID- 27379989 TI - Inflammatory potential of diet and risk of laryngeal cancer in a case-control study from Italy. AB - BACKGROUND: Besides tobacco and alcohol, diet and inflammation have been suggested to be important risk factors for laryngeal cancer. In this study, we examined the role of diet-associated inflammation, as estimated by dietary inflammatory index (DII) scores, in laryngeal cancer in a multicentre case control study conducted between 1992 and 2000 in Italy. METHODS: This study included 460 cases with incident, histologically confirmed laryngeal cancer, and 1,088 controls hospitalized for acute non-neoplastic diseases unrelated to tobacco and alcohol consumption. DII scores were computed from a reproducible and valid 78-item food-frequency questionnaire. Logistic regression models controlling for age, sex, study center, education, body mass index, tobacco smoking, alcohol drinking, and non-alcohol energy intake were used to estimate odds ratios (ORs) and the corresponding 95 % confidence intervals (CIs). RESULTS: Subjects with higher DII scores (i.e., with a more pro-inflammatory diet) had a higher risk of laryngeal cancer. The OR was 3.30 (95 % CI 2.06, 5.28; p for trend <0.0001) for the highest versus the lowest DII quartile. When DII was considered as a continuous variable, the OR was 1.27 (95 % CI 1.15, 1.40) for a one-unit (9 % of the DII range) increase. Stratified analyses produced slightly stronger associations between DII and laryngeal cancer risk among Subjects <60 years old (ORquartile4vs1 = 4.68), overweight subjects (ORQuartile4vs1 = 3.62), and among those with higher education (ORQuartile4vs1 = 3.92). We also observed a strong combined effect of higher DII and tobacco smoking or alcohol consumption on risk of laryngeal cancer. Compared with non-smokers having low DII scores, the OR was 6.64 for smokers with high DII scores. Likewise, compared with non/moderate drinkers with low DII, the OR was 5.82 for heavy drinkers with high DII. CONCLUSION: These results indicate that a pro-inflammatory diet is associated with increased risk of laryngeal cancer. PMID- 27379991 TI - In Response to: "Esen E, Tas DA, Sizmaz S, et al. Evaluating Choroidal Characteristics in Systemic Sclerosis Using Enhanced Depth Imaging Optical Coherence Tomography". PMID- 27379990 TI - Vascular morphology differentiates prostate cancer mortality risk among men with higher Gleason grade. AB - BACKGROUND: Higher Gleason grade is associated with prostate cancer mortality; however, there is significant heterogeneity in this association. We evaluated whether vessel morphology, a biomarker of angiogenesis, aided in distinguishing mortality risks among men with high Gleason grading. METHODS: We characterized vessel morphology (area and irregularity) among 511 patients diagnosed with prostate cancer during 1986 to 2000, re-reviewed Gleason grade, and followed men through 2012. Men were grouped according to integrated vessel lumen irregularity and vessel area across Gleason grade. The more angiogenic group was identified as those with more irregular vessel lumen and smaller vessel area. Crude rates (95 % confidence intervals) and survival probability were estimated across Gleason grade and vessel morphology. RESULTS: During a median 14-year follow-up, 62 men developed bone metastases or died of prostate cancer. Lethality rates were uniformly low within Gleason grade categories 6 and 7(3 + 4), regardless of vessel morphology. However, among men with Gleason grades of 7(4 + 3) or 8-10, the more angiogenic group was associated with fourfold higher risk of lethal outcomes compared to those with less angiogenic potential. Ten-year survival probability ranged from 95 to 74 % according to the extent of vessel morphology (p < 0.0001, log-rank test). CONCLUSIONS: Vessel morphology may aid Gleason grading in predicting prostate cancer mortality risks among men diagnosed with high-grade Gleason cancers. PMID- 27379993 TI - [Not Available]. PMID- 27379994 TI - [Not Available]. PMID- 27379992 TI - Evaluation of brain ageing: a quantitative longitudinal MRI study over 7 years. AB - OBJECTIVES: T1 relaxometry is a promising tool for the assessment of microstructural changes during brain ageing. Previous cross-sectional studies demonstrated increasing T1 values in white and decreasing T1 values in grey matter over the lifetime. However, these findings have not yet been confirmed on the basis of a longitudinal study. In this longitudinal study over 7 years, T1 relaxometry was used to investigate the dynamics of age-related microstructural changes in older healthy subjects. METHODS: T1 mapping was performed in 17 healthy subjects (range 51-77 years) at baseline and after 7 years. Advanced cortical and white matter segmentation was used to determine mean T1 values in the cortex and white matter. RESULTS: The analysis revealed a decrease of mean cortical T1 values over 7 years, the rate of T1 reduction being more prominent in subjects with higher age. T1 decreases were predominantly localized in the lateral frontal, parietal and temporal cortex. In contrast, mean white matter T1 values remained stable. CONCLUSIONS: T1 mapping is shown to be sensitive to age related microstructural changes in healthy ageing subjects in a longitudinal setting. Data of a cohort in late adulthood and the senescence period demonstrate a decrease of cortical T1 values over 7 years, most likely reflecting decreasing water content and increased iron concentrations. KEY POINTS: * T1 mapping is sensitive to age-related microstructural changes in a longitudinal setting. * T1 decreases were predominantly localized in the lateral frontal, parietal and temporal cortex. * The rate of T1 reduction was more prominent in subjects with higher age. * These changes most likely reflect decreasing cortical water and increasing iron concentrations. PMID- 27379995 TI - Telemonitoring of Type 2 Diabetes Mellitus in Italy. AB - BACKGROUND: Type 2 diabetes mellitus (DM) affects 382 million people worldwide. INTRODUCTION: This study aimed at assessing whether telemonitoring (TM) of DM patients improves health-related quality of life (HRQoL). MATERIALS AND METHODS: As part of the RENEWING HEALTH project, 299 DM patients with HbA1c >7.0% were enrolled in a randomized controlled trial, with 208 patients in the TM group and 91 patients in the usual-care group. TM electronically transmitted glucose measurements to physicians during a 12-month follow-up. The SF-36v2 questionnaire was used to assess HRQoL. RESULTS: In a total of 243 patients analyzed, the study did not identify any clinically important improvement in HRQoL, our primary endpoint. There was no statistically significant difference in HbA1c between the two groups; however, outpatient visits and planned hospitalizations were significantly reduced in the TM group (p < 0.0001 and p = 0.02). DISCUSSION: The results regarding HRQoL might be, at least in part, an artifact stemming from the criteria used to select patients. TM reduced ambulatory visits and planned hospital admissions, an important result that plausibly reflects the fact that clinicians can strictly monitor their patients' health status without face-to face contacts. CONCLUSIONS: Enhancement of HRQoL should represent the most critical goal of DM healthcare delivery. Effects of TM on HRQoL of diabetic patients should be studied further. PMID- 27379996 TI - Interleukin-35 (IL-35) inhibits proliferation and promotes apoptosis of fibroblast-like synoviocytes isolated from mice with collagen-induced arthritis. AB - Rheumatoid arthritis (RA) is an inflammatory disorder of the joints that affects 0.5-1 % of adults. Excessive growth of the fibroblast-like synoviocytes (FLS) promotes hyperplasia of synovial tissues and causes its invasion into the bone and cartilage, which eventually causes deformity and dysfunction of affected joints. Interleukin 35 (IL-35) was shown to suppress the inflammatory responses to collagen-induced arthritis (CIA) via upregulation of T regulatory cells and suppression of T helper type 17 cells in a mouse model. To study the effects of IL-35 on the proliferation and apoptosis frequency of cultured FLS isolated from mice with CIA as well as to examine the effects of IL-35 on CIA in vivo. Thirty DBA/1 J mice, which are used as an animal model for RA, were divided randomly (ten mice per group) to a CIA group (collagen treatment), a CIA + IL-35 group (collagen and IL-35 treatments), and a control group (no treatment). Starting on the 24th day after collagen administration, IL-35 was injected intraperitoneally into mice of the CIA + IL-35 group once per day for 10 days. An arthritis index was calculated, and pathological analysis of synovial tissue was performed. FLS isolated from CIA mice were treated with various concentrations of IL-35 (12.5 100 ng/ml). The MTT assay was used to examine FLS proliferation, and apoptosis frequency of FLS was detected by flow cytometry. On day 24, the CIA mice began to exhibit arthritis symptoms, and the symptoms rapidly progressed with time. Treatment with IL-35 significantly alleviated arthritis symptoms and reduced the synovial tissue inflammation. In addition, IL-35 treatment inhibited proliferation and promoted apoptosis in cultured FLS from CIA mice in a dose dependent manner. IL-35 could ameliorate the symptoms of arthritis in the CIA mouse model in vivo and inhibited FLS proliferation while promoting FLS apoptosis in vitro, thereby exhibited the potential in inhibiting the progression of RA. PMID- 27379997 TI - Women's Reproductive History Before the Diagnosis of Incident Endometriosis. AB - BACKGROUND: Endometriosis is a gynecologic disease reported to be associated with infertility and, possibly, adverse pregnancy outcomes. While considerable research focuses on pregnancy outcomes following diagnosis and/or treatment, few data actually describe women's reproductive history before diagnosis for a more complete understanding of endometriosis and reproduction. MATERIALS AND METHODS: The study sample comprised 473 women (aged 18-44 years) undergoing laparoscopies or laparotomies, irrespective of surgical indication at 14 clinical sites, during the period 2007-2009. Upon enrollment and before surgery, women were queried about pregnancy intentions and the time required to become pregnant for planned pregnancies. Endometriosis was defined as surgically visualized disease. Using discrete time survival analysis, we estimated fecundability odds ratios (FORs) and 95% confidence intervals (CIs) to assess time to pregnancy (TTP) after adjusting for potential confounders (age, body composition, cigarette smoking, site). Generalized estimating equations accounted for multiple pregnancy attempts per woman. FORs <1.0 denote a longer TTP or diminished fecundity. RESULTS: Approximately 66% and 69% of women with and without endometriosis, respectively, reported having a planned pregnancy before surgery, respectively. After adjustment, an endometriosis diagnosis was associated with ~29% reduction in fecundity or a longer TTP across all pregnancy-trying attempts (adjusted FOR = 0.71; 95% CI 0.46-1.10). While FORs were consistently <1.0, irrespective of endometriosis staging, CIs included 1. CONCLUSIONS: Women with endometriosis had a longer TTP than unaffected women, irrespective of disease severity, although the findings did not achieve significance. Prior reproductive history may be informative for predicting fecundity and pregnancy outcomes following diagnosis/treatment. PMID- 27379998 TI - Corona sign: manifestation of peripheral corneal epithelial edema as a possible marker of the progression of corneal endothelial dysfunction. AB - PURPOSE: To describe a characteristic form of the corona sign and its clinical relevance to the degree of corneal endothelial decompensation and investigate the underlying mechanism using a rabbit model. METHODS: These observational cases include 31 patients undergoing penetrating keratoplasty (PKP) and 15 patients undergoing Descemet stripping automated endothelial keratoplasty (DSAEK) with special attention to the circumferentially developed corneal epithelial edema. We also conducted a laboratory observation of horizontal water flow in the rabbit cornea. RESULTS: We consistently observed the corona sign at the superior periphery during the initial stage of corneal endothelial decompensation after PKP. With progressive corneal endothelial cellular loss, the epithelial edema gradually expanded circumferentially in the periphery. The endothelial cellular density associated with the corona sign significantly (P < 0.01) decreased compared with that without the sign. The endothelial cellular density decreased significantly (P < 0.05) in cases with a circumferential corona sign compared with a superior corona sign. After DSAEK, however, the corneal epithelial edema subsided from the center but persisted peripherally as a corona sign in all cases. By 3 months postoperatively, the epithelial edema was confined to the superior periphery along with uneventful corneal endothelial healing. Rabbit experiments showed that total corneal endothelial decompensation decreased the horizontal intracorneal water migration (Inoue-Ohashi phenomenon) in the corneal periphery and induced peripheral corneal edema. CONCLUSIONS: The slit-lamp microscopic findings of the corona-like epithelial edema in the peripheral cornea are associated with the stage of corneal endothelial function. To support this, the developmental mechanism of the corona sign was demonstrated experimentally. PMID- 27380000 TI - Implementation of the National Acupuncture Detoxification Association Protocol in a Community Mental Health Setting. AB - OBJECTIVES: The purpose of this study was to evaluate patients' satisfaction with National Acupuncture Detoxification Association (NADA) acupuncture services in two community mental health settings. DESIGN: Cross-sectional, mixed-methods study. Participants who had participated in acupuncture services were given a survey that contained both quantitative and qualitative items. SETTINGS: Participants were recruited from two community mental health centers in the New England area. PARTICIPANTS: Fifty patients enrolled in community mental health centers. They were eligible to participate in the study if they had attended at least one acupuncture session. Twenty-five percent of the sample comprised monolingual Spanish-speakers. INTERVENTIONS: Participants had received at least one session of auricular acupuncture according to the NADA protocol. OUTCOME MEASURES: Participants completed a satisfaction survey that contained 10 items in English or Spanish. RESULTS: On a 5-point Likert scale, participants reported that they found acupuncture beneficial (mean, 4.35; standard deviation, 0.78). Data from the qualitative items were analyzed and revealed two prominent themes: (1) relaxation and (2) improved focus and concentration. Eight percent of the sample reported no benefit of acupuncture during the session. CONCLUSION: Overall, the patients reported high satisfaction with the acupuncture services received, as well as a variety of benefits (relaxation, improved focus and concentration, improvement in psychiatric symptoms or substance use craving, and somatic benefits). PMID- 27379999 TI - The role of Prdx6 in the protection of cells of the crystalline lens from oxidative stress induced by UV exposure. AB - PURPOSE: The immediate aim of this study was to investigate alterations in peroxiredoxin (Prdx) 6 at posttranslational levels, and the levels of protein oxidation, lipid peroxidation, and reactive oxygen species (ROS) in lens epithelial cells (LECs) after exposure to severe oxidative stress, such as ultraviolet-B (UV-B). Our ultimate aim was to provide new information on antioxidant defenses in the lens and their regulation, thereby broadening existing knowledge of the role of Prdx6 in lens physiology and pathophysiology. METHODS: The expression of the hyperoxidized form of Prdx6 and oxidation of protein were analyzed by western blotting and the OxyBlot assay in human LECs (hLECs). ROS levels were quantified using DCFH-DA dye, and cell viability was quantified by the MTS and TUNEL assays. To evaluate the protective effect of Prdx6, we cultured lenses with or without the TAT transduction domain (TAT-HA Prdx6) and observed (and photographed) the cultures at specified time-points after the exposure to UV-B for the development of opacity. RESULTS: Prdx6 in hLECs was hyperoxidized after exposure to high amounts of UV-B. UV-B treatment of hLECs increased the levels of cell death, protein oxidation, and ROS. hLECs exposed to UV-B showed higher levels of ROS, which could be reduced by the application of extrinsic TAT-HA-Prdx6, attenuating UV-B-induced lens opacity and apoptotic cell death. CONCLUSION: Excessive oxidative stress induces the hyperoxidation of Prdx6 and may reduce the ability of Prdx6 to protect LECs against ROS or stresses. Because extrinsic Prdx6 could attenuate UV-B-induced abuse, this molecule may have a potential in preventing cataractogenesis. PMID- 27380001 TI - Adaptive fractionated stereotactic Gamma Knife radiotherapy of meningioma using integrated stereotactic cone-beam-CT and adaptive re-planning (a-gkFSRT). AB - OBJECTIVE: The Gamma Knife Icon (Elekta AB, Stockholm, Sweden) allows frameless stereotactic treatment using a combination of cone beam computer tomography (CBCT), a thermoplastic mask system, and an infrared-based high-definition motion management (HDMM) camera system for patient tracking during treatment. We report on the first patient with meningioma at the left petrous bone treated with adaptive fractionated stereotactic radiotherapy (a-gkFSRT). METHODS: The first patient treated with Gamma Knife Icon at our institute received MR imaging for preplanning before treatment. For each treatment fraction, a daily CBCT was performed to verify the actual scull/tumor position. The system automatically adapted the planned shot positions to the daily position and recalculated the dose distribution (online adaptive planning). During treatment, the HDMM system recorded the intrafractional patient motion. Furthermore, the required times were recorded to define a clinical treatment slot. RESULTS: Total treatment time was around 20 min. Patient positioning needed 0.8 min, CBCT positioning plus acquisition 1.65 min, CT data processing and adaptive planning 2.66 min, and treatment 15.6 min. The differences for the five daily CBCTs compared to the reference are for rotation: -0.59 +/- 0.49 degrees /0.18 +/- 0.20 degrees /0.05 +/- 0.36 degrees and for translation: 0.94 +/- 0.52 mm/-0.08 +/- 0.08 mm/-1.13 +/- 0.89 mm. Over all fractions, an intrafractional movement of 0.13 +/- 0.04 mm was observed. CONCLUSION: The Gamma Knife Icon allows combining the accuracy of the stereotactic Gamma Knife system with the flexibility of fractionated treatment with the mask system and CBCT. Furthermore, the Icon system introduces a new online patient tracking system to the clinical routine. The interfractional accuracy of patient positioning was controlled with a thermoplastic mask and CBCT. PMID- 27380002 TI - Incidence, risk factors, and the impact of allograft pyelonephritis on renal allograft function. AB - BACKGROUND: The impact of allograft pyelonephritis (AGPN) on renal allograft function is controversial. In this study, we evaluated the incidence, risk factors, and the impact of AGPN on renal allograft function. METHODS: Retrospective cohort study in adult renal allograft recipients with 1-year follow up after transplantation (Tx). Renal allograft function was evaluated by estimated glomerular filtration rate (eGFR) (by Modification of Diet in Renal Disease formula) and 24-h urine protein excretion. RESULTS: A total of 431 renal allograft recipients were analyzed; 57 (13.2%) developed AGPN within 1 year after Tx. Median time between Tx and AGPN was 50 days. Risk factors for AGPN were the presence of a urological catheter (odds ratio [OR] = 18.93, 95% confidence interval [CI] = 8.00-44.81, P < 0.001) and preceding asymptomatic bacteriuria (ASB) (OR = 2.16, 95% CI = 1.20-3.90, P = 0.009). In 72.7%, the causative microorganism of ASB was identical to that of the succeeding AGPN episode. Multivariable linear regression analysis showed that experiencing AGPN did not decrease the eGFR (P = 0.61) nor did increased proteinuria (P = 0.29) 1 year after Tx. For the eGFR, an interaction was found between AGPN/bacteriuria (BU) and acute rejection (AR): the group experiencing BU preceding AR had significantly (P < 0.001) lower eGFR compared with the group that experienced only AR (21 mL/min/1.73 m2 vs. 48 mL/min/1.73 m2 ), as a result of increased prevalence of combined rejections within the BU group. CONCLUSION: Indwelling urological catheters and preceding ASB are associated with developing AGPN. An incident of AGPN itself does not impair renal allograft function 1 year after Tx. However, a relevant interaction occurs between BU and AR, in which the sequence of occurrence of these 2 events synergistically impairs the eGFR. PMID- 27380004 TI - Use of Language Sample Analysis by School-Based SLPs: Results of a Nationwide Survey. AB - PURPOSE: This article examines use of language sample analysis (LSA) by school based speech-language pathologists (SLPs), including characteristics of language samples, methods of transcription and analysis, barriers to LSA use, and factors affecting LSA use, such as American Speech-Language-Hearing Association certification, number of years' experience, and caseload characteristics. METHOD: School-based SLPs responded to an invitation to complete an electronic survey related to LSA. RESULTS: One third of respondents indicated they did not use LSA during the 2012-2013 school year. SLPs who served middle and high school students were less likely to use LSA. Most respondents reported using conversation to analyze fewer than 10 samples and transcribing in real time. Additional analyses revealed that SLPs who had 3 or fewer years of experience and who analyzed fewer than 20 language samples per year were statistically less likely to report using real-time transcription. The most frequently cited barrier to using LSA was "LSA is too time-consuming." CONCLUSION: Many school-based SLPs do not routinely use LSA. Further, many did not report engaging in evidence-based practices, such as recording samples, using established protocols, or using tasks designed to elicit complex syntax. These results indicate a continued need for professional development regarding evidenced-based practices relative to LSA use. PMID- 27380005 TI - [Not Available]. PMID- 27380003 TI - The combination of trastuzumab and pertuzumab administered at approved doses may delay development of trastuzumab resistance by additively enhancing antibody dependent cell-mediated cytotoxicity. AB - Although the recently concluded CLEOPATRA trial showed clinical benefits of combining trastuzumab and pertuzumab for treating HER2-positive metastatic breast cancer, trastuzumab monotherapy is still the mainstay in adjuvant settings. Since trastuzumab resistance occurs in over half of these cancers, we examined the mechanisms by which treatment of intrinsically trastuzumab-resistant and sensitive tumors can benefit from the combination of these antibodies. F(ab')2 of both trastuzumab and pertuzumab were generated and validated in order to separately analyze antibody-dependent cell-mediated cytotoxicity (ADCC)-based and direct biological effects of the antibodies. Compared to monotherapy, combination of the two antibodies at clinically permitted doses enhanced the recruitment of natural killer cells responsible for ADCC, and significantly delayed the outgrowth of xenografts from intrinsically trastuzumab-resistant JIMT-1 cells. Antibody dose-response curves of in vitro ADCC showed that antibody-mediated killing can be saturated, and the two antibodies exert an additive effect at sub saturation doses. Thus, the additive effect in vivo indicates that therapeutic tissue levels likely do not saturate ADCC. Additionally, isobole studies with the in vitro trastuzumab-sensitive BT-474 cells showed that the direct biological effect of combined treatment is additive, and surpasses the maximum effect of either monotherapy. Our results suggest the combined therapy is expected to give results that are superior to monotherapy, whatever the type of HER2-positive tumor may be. The combination of both antibodies at maximum clinically approved doses should thus be administered to patients to recruit maximum ADCC and cause maximum direct biological growth inhibition. PMID- 27380006 TI - [Not Available]. PMID- 27380007 TI - [Not Available]. PMID- 27380008 TI - [Not Available]. PMID- 27380009 TI - [Not Available]. PMID- 27380010 TI - Effects of inaccurate small field dose measurements on calculated treatment doses. AB - Given the difficulty and potential time- or financial-costs associated with accurate small field dosimetry, this study aimed to establish the clinical necessity of obtaining accurate small field output factor measurements and to evaluate the effects on planned doses that could arise if accurate measurements are not used in treatment planning dose calculations. Isocentre doses, in heterogeneous patient anatomy, were calculated and compared for 571 beams from 48 clinical radiotherapy treatments, using a clinical radiotherapy treatment planning system, with reference to two different sets of beam configuration data. One set of beam configuration data included field output factors (total scatter factors) from precisely positioned and response-corrected diode measurements and the other included field output factors measured using a conventional technique that would have been better suited to larger field measurements. Differences between the field output factor measurements made with the two different techniques equated to 14.2 % for the 6 [Formula: see text] 6 mm[Formula: see text] field, 1.8 % for the 12 [Formula: see text] 12 mm[Formula: see text] field, and less than 0.5 % for the larger fields. This led to isocentre dose differences of up to 3.3 % in routine clinical fields smaller than 9 mm across and and up to 11 % in convoluted fields smaller than 15 mm across. If field widths smaller than 15 mm are used clinically, then accurate measurement (or-remeasurement) of small field output factors in the treatment planning system's beam data is required in order to achieve dose calculation accuracy within 3 %. If such measurements are not completed, then errors in excess of 10 % may occur if very small, narrow, concave or convoluted treatment fields are used. PMID- 27380011 TI - The rested relationship: Sleep benefits marital evaluations. AB - Remaining satisfied with a relationship often requires thinking in ways that use self-regulatory resources-satisfied couples discount undesirable experiences when forming global evaluations of the relationship. Nevertheless, recent work indicates that the self-regulatory resources required to engage in these processes are limited. Although consuming new energy may be one way to replenish these limited resources, sleep is another. The current study used a daily diary study of 68 newlywed couples to examine the implications of sleep for daily marital evaluations. Every day for up to 7 days, both members of the couples reported their evaluations of their interpersonal specific experiences, global relationship satisfaction, and amount of sleep. Multilevel analysis revealed that spouses were more satisfied on days after which they had slept for a longer period of time. Furthermore, sleep also buffered husbands', but not wives', marital satisfaction against the implications of negative specific evaluations husbands were better able to remain more globally satisfied despite negative evaluations of specific aspects of the relationship on days following more sleep. These findings suggest that sleep may offer self-regulatory benefits and should thus be incorporated into existing interpersonal models that highlight the importance of self-regulation. (PsycINFO Database Record PMID- 27380012 TI - [Not Available]. PMID- 27380014 TI - A protocol to determine dermal absorption of xenobiotica through human skin in vitro. AB - Determination of the absorption through the skin is of utmost importance for predictions of benefits and of risks of dermal exposure to xenobiotica. In order to allow for flexibility, the OECD guideline for the determination of skin absorption for different purposes and use conditions (OECD guideline 428 combined with the Technical Guidance Document 28) is inexplicit; hence, different experimental procedures are used which may lead to limited comparability of study results. The here described protocol provides explicit guidance, whereas it does not invalidate other procedures within the frame of the OECD guideline since uncritical versus critical steps are differentiated. Optimizations are presented which finally led to a precisely defined protocol allowing for enhanced comparability of future study results. Some salient properties of this protocol are the storage of the prepared diffusion cell overnight refrigerated in the presence of a protease inhibitor cocktail and include investigation of the integrity of the skin sample as well as the removal of the upper stratum corneum by tape strips under standardized conditions. PMID- 27380013 TI - Development of synaptic connectivity in the retinal direction selective circuit. AB - Direction selectivity is a classic neuronal computation that has been described in many different sensory systems. The circuit basis of this computation is perhaps best understood in the retina, where direction selectivity is the result of asymmetric connectivity patterns between excitatory and inhibitory circuit components. Retinal direction selective circuits emerge before eye-opening, though components of the circuit undergo refinement after vision begins. These features make the direction selective circuit a rich model in which to investigate neuronal circuit assembly. In this Opinion, we highlight recent experiments investigating the contribution of various molecular cues, as well as neuronal activity, to the development of the retinal direction selective circuit. PMID- 27380015 TI - Correction: Safety and Efficacy of Methotrexate in Psoriasis: A Meta-Analysis of Published Trials. AB - [This corrects the article DOI: 10.1371/journal.pone.0153740.]. PMID- 27380016 TI - Synthesis and characterization of Mn intercalated Mg-Al hydrotalcite. AB - Mn intercalated hydrotalcite was prepared using a reconstruction method. And Mn intercalation was confirmed by XRD, FTIR, and thermal analyses. The different valences of Mn were present as determined by XPS. Calcination slightly promoted the isomorphic replacement of Mn(2+) and Mn(3+) for Mg(2+) and Al(3+), especially the replacement of Mn(2+) for Mg(2+) and Al(3+), and to some extent, reduced Mn intercalation. Ultrasonic treatment significantly increased Mn intercalation in permanganate form (Mn(7+)), and promoted the replacement of Mn(2+) for Mg(2+) and Al(3+). XRF analysis showed that ultrasonic treatment decreased the unbalanced layer charge of Mn intercalated hydrotalcite, while prolonged calcination increased it. These results may provide guidance on the preparation and application of Mn intercalated hydrotalcite. Extended calcination time and ultrasonic vibration increased the interlayer spacing of hydrotalcite, as a result of reduction in layer charge. As the layer charge was not completely balanced after Mn intercalation, a certain amount of CO3(2-) was re-adsorbed into the interlayer space. Mn-hydrotalcites with different layer charges, different contents of Mn with varying valences are expected to have different performances in the process of adsorption, degradation, and catalysis. PMID- 27380019 TI - Seronegative Myasthenia Gravis-A Vanishing Disorder? PMID- 27380020 TI - Exhaled breath condensate for lung cancer protein analysis: a review of methods and biomarkers. AB - Lung cancer is a leading cause of cancer-related deaths worldwide, and is considered one of the most aggressive human cancers, with a 5 year overall survival of 10-15%. Early diagnosis of lung cancer is ideal; however, it is still uncertain as to what technique will prove successful in the systematic screening of high-risk populations, with the strongest evidence currently supporting low dose computed tomography (LDCT). Analysis of exhaled breath condensate (EBC) has recently been proposed as an alternative low risk and non-invasive screening method to investigate early-stage neoplastic processes in the airways. However, there still remains a relative paucity of lung cancer research involving EBC, particularly in the measurement of lung proteins that are centrally linked to pathogenesis. Considering the ease and safety associated with EBC collection, and advances in the area of mass spectrometry based profiling, this technology has potential for use in screening for the early diagnosis of lung cancer. This review will examine proteomics as a method of detecting markers of neoplasia in patient EBC with a particular emphasis on LC, as well as discussing methodological challenges involving in proteomic analysis of EBC specimens. PMID- 27380018 TI - Identification and expression profiling of DNA methyltransferases during development and stress conditions in Solanaceae. AB - DNA methyltransferase (DMTase) enzymes contribute to plant development and stress responses by de novo establishment and subsequent maintenance of DNA methylation during replication. However, the molecular mechanism underlying this activity remains obscure, especially in crop species. Using DMTase homolog complement in six Solanaceae species, we demonstrated here that their number remained conserved in Solanum lineage, whereas it was expanded in both pepper and Nicotiana benthamiana. Non-synonymous vs synonymous (Ka/Ks) substitution ratio revealed that most of the Solanaceous DMTase homologs undergo purifying selection. The genomic sequences of tomato DMT homologs in its wild relative, Solanum pennellii, remained highly conserved in their exons and methyltransferase domains. Structure analysis further revealed highly similar folding of DMTase homologs and conservation in the residues participating in protein-protein interaction in Solanum lineage, whereas a considerable diversification was observed of pepper homologs. Transcript profiling of DMTases highlighted both similar and distinct expression patterns of tomato homologs in other species during fruit development and stress responses. Overall, our analysis provides a strong basis for in-depth exploration of both conserved as well as distinct functions of tomato DMTase homologs in other economically important Solanaceae species. PMID- 27380022 TI - Low acid hydrothermal fractionation of Giant Miscanthus for production of xylose rich hydrolysate and furfural. AB - Low acid hydrothermal (LAH) fractionation was developed for the effective recovery of hemicellulosic sugar (mainly xylose) from Miscanthus sacchariflorus Goedae-Uksae 1 (M. GU-1). The xylose yield was maximized at 74.75% when the M. GU 1 was fractionated at 180 degrees C and 0.3wt.% of sulfuric acid for 10min. At this condition, the hemicellulose (mainly xylan) degradation was 86.41%. The difference between xylan degradation and xylose recovery yield, i.e., xylan loss, was 11.66%, as indicated by the formation of decomposed products. The furfural, the value added biochemical product, was also obtained by 0.42g/L at this condition, which was 53.82% of furfural production yield based on the xylan loss. After then, the furfural production continued to increase to a maximum concentration of 1.87g/L, at which point the xylan loss corresponded to 25.87%. PMID- 27380023 TI - Decomposition Dynamics and Changes in Chemical Composition of Wheat Straw Residue under Anaerobic and Aerobic Conditions. AB - Soil aeration is a crucial factor that regulates crop residue decomposition, and the chemical composition of decomposing crop residues may change the forms and availability of soil nutrients, such as N and P. However, to date, differences in the chemical composition of crop straw residues after incorporation into soil and during its decomposition under anaerobic vs. aerobic conditions have not been well documented. The objective of the present study was to assess changes in the C-containing functional groups of wheat straw residue during its decomposition in anaerobic and aerobic environments. A 12-month incubation experiment was carried out to investigate the temporal variations of mass, carbon, and nitrogen loss, as well as changes in the chemical composition of wheat (Triticum aestivum L) straw residues under anaerobic and aerobic conditions by measuring C-containing functional groups using solid state nuclear magnetic resonance (NMR) spectroscopy. The residual mass, carbon content, and nitrogen content of the straw residue sharply declined during the initial 3 months, and then slowly decreased during the last incubation period from 3 to 12 months. The decomposition rate constant (k) for mass loss under aerobic conditions (0.022 d 1) was higher than that under anaerobic conditions (0.014 d-1). The residual mass percentage of cellulose and hemicellulose in the wheat straw gradually declined, whereas that of lignin gradually increased during the entire 12-month incubation period. The NMR spectra of C-containing functional groups in the decomposing straw under both aerobic and anaerobic conditions were similar at the beginning of the incubation as well as at 1 month, 6 months, and 12 months. The main alterations in C-containing functional groups during the decomposition of wheat straw were a decrease in the relative abundances of O-alkyl C and an increase in the relative abundances of alkyl C, aromatic C and COO/N-C = O functional groups. The NMR signals of alkyl C and aromatic C in decomposing wheat straw residues under anaerobic condition were higher than those under aerobic conditions. The higher mass percentages of lignin and the higher signals of aromatic C and alkyl C functional groups in decomposing wheat residues under anaerobic conditions than under aerobic conditions were due to the slower decomposition rates of aryl C and alkyl C in wheat straw residues under anaerobic conditions. PMID- 27380021 TI - Sexual Preferences in Nutrient Utilization Regulate Oxygen Consumption and Reactive Oxygen Species Generation in Schistosoma mansoni: Potential Implications for Parasite Redox Biology. AB - Schistosoma mansoni, one of the causative agents of human schistosomiasis, has a unique antioxidant network that is key to parasite survival and a valuable chemotherapeutic target. The ability to detoxify and tolerate reactive oxygen species increases along S. mansoni development in the vertebrate host, suggesting that adult parasites are more exposed to redox challenges than young stages. Indeed, adult parasites are exposed to multiple redox insults generated from blood digestion, activated immune cells, and, potentially, from their own parasitic aerobic metabolism. However, it remains unknown how reactive oxygen species are produced by S. mansoni metabolism, as well as their biological effects on adult worms. Here, we assessed the contribution of nutrients and parasite gender to oxygen utilization pathways, and reactive oxygen species generation in whole unpaired adult S. mansoni worms. We also determined the susceptibilities of both parasite sexes to a pro-oxidant challenge. We observed that glutamine and serum importantly contribute to both respiratory and non respiratory oxygen utilization in adult worms, but with different proportions among parasite sexes. Analyses of oxygen utilization pathways revealed that respiratory rates were high in male worms, which contrast with high non respiratory rates in females, regardless nutritional sources. Interestingly, mitochondrial complex I-III activity was higher than complex IV specifically in females. We also observed sexual preferences in substrate utilization to sustain hydrogen peroxide production towards glucose in females, and glutamine in male worms. Despite strikingly high oxidant levels and hydrogen peroxide production rates, female worms were more resistant to a pro-oxidant challenge than male parasites. The data presented here indicate that sexual preferences in nutrient metabolism in adult S. mansoni worms regulate oxygen utilization and reactive oxygen species production, which may differently contribute to redox biology among parasite sexes. PMID- 27380025 TI - Computational growth model of breast microcalcification clusters in simulated mammographic environments. AB - BACKGROUND: When screening for breast cancer, the radiological interpretation of mammograms is a difficult task, particularly when classifying precancerous growth such as microcalcifications (MCs). Biophysical modeling of benign vs. malignant growth of MCs in simulated mammographic backgrounds may improve characterization of these structures METHODS: A mathematical model based on crystal growth rules for calcium oxide (benign) and hydroxyapatite (malignant) was used in conjunction with simulated mammographic backgrounds, which were generated by fractional Brownian motion of varying roughness and quantified by the Hurst exponent to mimic tissue of varying density. Simulated MC clusters were compared by fractal dimension, average circularity of individual MCs, average number of MCs per cluster, and average cluster area. RESULTS: Benign and malignant clusters were distinguishable by average circularity, average number of MCs per cluster, and average cluster area with p<0.01 across all Hurst exponent values considered. Clusters were distinguishable by fractal dimension with p<0.05 in low Hurst exponent environments. As the Hurst exponent increased (tissue density increased) benign and malignant MCs became indistinguishable by fractal dimension. CONCLUSIONS: The fractal dimension of MCs changes with breast tissue density, which suggests tissue environment plays a role in regulating MC growth. Benign and malignant MCs are distinguishable in all types of tissue by shape, size, and area, which is consistent with findings in the literature. These results may help to better understand the effects of the tissue environment on tumor progression, and improve classification of MCs in mammograms via computer-aided diagnosis. PMID- 27380024 TI - Specific MAPK-Associated MicroRNAs in Serum Differentiate Pancreatic Cancer from Autoimmune Pancreatitis. AB - Pancreatic ductal adenocarcinoma (PDAC) is difficult to distinguish from autoimmune pancreatitis (AIP) because of their clinical and radiological similarities, and therefore simple and minimally invasive surrogate markers for differential diagnosis would be useful. In our previous studies, we identified four microRNAs (miRNAs)-miR-7, miR-34a, miR-181d, and miR-193b -as MAPK associated microRNAs whose expression was altered significantly with upregulation of the MAPK signaling pathway. Recently it has been reported that these miRNAs could be used as biomarkers in serum samples for accurate diagnosis of pancreatic lesions. The aim of the present study was to evaluate whether these MAPK associated miRNAs in serum could be used as biomarkers for differentiating PDAC from AIP. We enrolled 69 patients with PDAC, 26 with intraductal papillary mucinous neoplasm (IPMN) and 15 with AIP. The expression of MAPK-associated miRNAs in serum was measured by quantitative real-time PCR. The 2-DeltaCT method was used to quantify the expression of miRNAs, and the data were normalized using spiked-in synthetic cel-miR-39. Patients with PDAC or IPMN showed significantly higher amounts of serum MAPK-associated miRNAs than those with AIP (p<0.009 for miR-7, p<0.002 for miR-34a, p<0.001 for miR-181d, p<0.002 for miR-193b). ROC curve analysis demonstrated that these miRNAs had an area under the ROC curve (AUC) of 0.723-0.882 for differentiation between PDAC or IPMN from AIP. Furthermore, serum miR-181d was significantly associated with the presence of metastasis in patients with PDA (p = 0.014). Serum MAPK-associated miRNAs could be novel noninvasive biomarkers for differentiation between PDAC or IPMN and AIP. PMID- 27380027 TI - Sensitization to Inhalant Allergens in Schoolchildren with Special Reference to Passive Smoking. PMID- 27380026 TI - MU Opioid Receptor Expression after Morphine Administration Is Regulated by miR 212/132 Cluster. AB - Since their discovery, miRNAs have emerged as a promising therapeutical approach in the treatment of several diseases, as demonstrated by miR-212 and its relation to addiction. Here we prove that the miR-212/132 cluster can be regulated by morphine, through the activation of mu opioid receptor (Oprm1). The molecular pathways triggered after morphine administration also induce changes in the levels of expression of oprm1. In addition, miR-212/132 cluster is actively repressing the expression of mu opioid receptor by targeting a sequence in the 3' UTR of its mRNA. These findings suggest that this cluster is closely related to opioid signaling, and function as a post-transcriptional regulator, modulating morphine response in a dose dependent manner. The regulation of miR-212/132 cluster expression is mediated by MAP kinase pathway, CaMKII-CaMKIV and PKA, through the phosphorylation of CREB. Moreover, the regulation of both oprm1 and of the cluster promoter is mediated by MeCP2, acting as a transcriptional repressor on methylated DNA after prolonged morphine administration. This mechanism explains the molecular signaling triggered by morphine as well as the regulation of the expression of the mu opioid receptor mediated by morphine and the implication of miR-212/132 in these processes. PMID- 27380028 TI - Dual Combined Real-Time Reverse Transcription Polymerase Chain Reaction Assay for the Diagnosis of Lyssavirus Infection. AB - The definitive diagnosis of lyssavirus infection (including rabies) in animals and humans is based on laboratory confirmation. The reference techniques for post mortem rabies diagnosis are still based on direct immunofluorescence and virus isolation, but molecular techniques, such as polymerase chain reaction (PCR) based methods, are increasingly being used and now constitute the principal tools for diagnosing rabies in humans and for epidemiological analyses. However, it remains a key challenge to obtain relevant specificity and sensitivity with these techniques while ensuring that the genetic diversity of lyssaviruses does not compromise detection. We developed a dual combined real-time reverse transcription polymerase chain reaction (combo RT-qPCR) method for pan-lyssavirus detection. This method is based on two complementary technologies: a probe-based (TaqMan) RT-qPCR for detecting the RABV species (pan-RABV RT-qPCR) and a second reaction using an intercalating dye (SYBR Green) to detect other lyssavirus species (pan-lyssa RT-qPCR). The performance parameters of this combined assay were evaluated with a large panel of primary animal samples covering almost all the genetic variability encountered at the viral species level, and they extended to almost all lyssavirus species characterized to date. This method was also evaluated for the diagnosis of human rabies on 211 biological samples (positive n = 76 and negative n = 135) including saliva, skin and brain biopsies. It detected all 41 human cases of rabies tested and confirmed the sensitivity and the interest of skin biopsy (91.5%) and saliva (54%) samples for intra-vitam diagnosis of human rabies. Finally, this method was successfully implemented in two rabies reference laboratories in enzootic countries (Cambodia and Morocco). This combined RT-qPCR method constitutes a relevant, useful, validated tool for the diagnosis of rabies in both humans and animals, and represents a promising tool for lyssavirus surveillance. PMID- 27380029 TI - Allele-Specific Transcriptome and Methylome Analysis Reveals Stable Inheritance and Cis-Regulation of DNA Methylation in Nasonia. AB - Gene expression divergence between closely related species could be attributed to both cis- and trans- DNA sequence changes during evolution, but it is unclear how the evolutionary dynamics of epigenetic marks are regulated. In eutherian mammals, biparental DNA methylation marks are erased and reset during gametogenesis, resulting in paternal or maternal imprints, which lead to genomic imprinting. Whether DNA methylation reprogramming exists in insects is not known. Wasps of the genus Nasonia are non-social parasitoids that are emerging as a model for studies of epigenetic processes in insects. In this study, we quantified allele-specific expression and methylation genome-wide in Nasonia vitripennis and Nasonia giraulti and their reciprocal F1 hybrids. No parent-of origin effect in allelic expression was found for >8,000 covered genes, suggesting a lack of genomic imprinting in adult Nasonia. As we expected, both significant cis- and trans- effects are responsible for the expression divergence between N. vitripennis and N. giraulti. Surprisingly, all 178 differentially methylated genes are also differentially methylated between the two alleles in F1 hybrid offspring, recapitulating the parental methylation status with nearly 100% fidelity, indicating the presence of strong cis-elements driving the target of gene body methylation. In addition, we discovered that total and allele-specific expression are positively correlated with allele-specific methylation in a subset of the differentially methylated genes. The 100% cis-regulation in F1 hybrids suggests the methylation machinery is conserved and DNA methylation is targeted by cis features in Nasonia. The lack of genomic imprinting and parent-of-origin differentially methylated regions in Nasonia, together with the stable inheritance of methylation status between generations, suggests either a cis regulatory motif for methylation at the DNA level or highly stable inheritance of an epigenetic signal in Nasonia. PMID- 27380030 TI - The effect of acute taurine ingestion on 4-km time trial performance in trained cyclists. AB - Taurine (TAU) has been shown to improve exercise time to exhaustion and 3-km running performance; however, no studies have considered the effect of acute TAU ingestion on short duration cycling time trial (TT) performance. The aim of this study was to determine the effects of a single oral acute dose of 1000 mg of TAU on a laboratory simulated 4-km cycling TT. Eleven trained male cyclists performed three, 4-km TTs. The first of the trials was a familiarisation, followed by two subsequent trials which were performed two hours after the consumption of either 1000 mg of TAU or placebo (P), using a double-blind randomised crossover design. Capillary blood samples were obtained prior to the start and immediately after each TT for the measurement of lactate, pH and HCO3-. There was no effect of TAU (p = 0.731, d = 0.151) on performance (390 +/- 27 and 388 +/- 21 s for TAU and P, respectively), nor were there any condition main effects for VO2, lactate, pH, or HCO3- (p > 0.05) despite post TT changes in lactate (7.3 +/- 2.5 mmol l-1, p < 0.001, d = 2.86, 7.6 +/- 2.0 mmol l-1 p < 0.001, d = 3.75); pH (-0.255 +/- 0.1, p < 0.001, d = 2.62, -0.258 +/- 0.09, p < 0.001, d = 2.87); HCO3- (-13.58 +/- 2.7 mmol l-1, p < 0.001, d = 5.04 vs. -13.36 +/- 2.3, p < 0.001, d = 5.72 for TAU and P, respectively). The findings of this study suggest that a pre-exercise dose of 1000 mg TAU offers no performance advantage during 4-km TT nor does it alter the blood buffering responses in trained cyclists. PMID- 27380031 TI - Strategies towards in vivo imaging of active transglutaminase type 2 using positron emission tomography. AB - Transglutaminase type 2 (TG2) is increasingly linked to the pathogenesis of several diseases, such as celiac disease, cancer, and fibrotic and neurodegenerative diseases. In parallel with becoming an attractive target for therapy, interest in the development of compounds for in vivo imaging of TG2 is rising. Such imaging biomarkers might assist in clarifying the role of TG2 in pathology and in monitoring TG2 inhibition in vivo and thus assist in drug development. In this review, the latest results together with various strategies in TG2 PET tracer development are discussed, including radiolabelling of irreversible and reversible active-site inhibitors, as well as allosteric inhibitors, acyl-donor and acyl-acceptor substrates, and anti-TG2 monoclonal antibodies. PMID- 27380032 TI - Antioxidant Behavior of Olive Phenolics in Oil-in-Water Emulsions. AB - The effect of the surrounding molecular environment (beta-lactoglobulin as an emulsion stabilizer and maltodextrin as a viscosity modifier) on the antioxidant activity of three olive oil phenolic compounds (PCs) in olive oil-in-water emulsions was investigated. Oxidation potential, phenolic partitioning, and radical quenching capacity were assessed in solution and in emulsion for oleuropein, hydroxytyrosol, and tyrosol; the influence of beta-lactoglobulin and maltodextrin concentration was also evaluated. Finally, the observed properties were related to the oxidative stability of the emulsions containing the PCs to explain their behavior. The order hydroxytyrosol > oleuropein > tyrosol was observed among the antioxidants for both oxidation potential and radical quenching activity. Radical quenching capacity in emulsion and anodic potential were complementary indices of antioxidant effectiveness. As the intrinsic susceptibility of an antioxidant to oxidation expressed by its anodic potential decreased, the environmental conditions (molecular interactions and changes in continuous phase viscosity) played a major role in the antioxidant effectiveness in preventing hydroperoxide decomposition. PMID- 27380033 TI - Simple obstructive sleep apnea patients without hypertension or diabetes accelerate kidney dysfunction: a population follow-up cohort study from Taiwan. AB - BACKGROUNDS: Obstructive sleep apnea (OSA) is common in patients on hemodialysis, but its correlation with chronic kidney disease (CKD) is not clear. We aimed to clarify the relationship between OSA without hypertension or diabetes and incidence of CKD in Taiwan. METHODS: This population-based cohort study consisted of patients with newly diagnosed OSA between 2000 and 2009. The comparison cohort was matched for age, sex, diabetes mellitus, and hypertension. All subjects previously diagnosed with acute or chronic kidney disease were excluded. The primary end point was newly diagnosed CKD. RESULTS: We identified 6866 subjects with OSA during the 10-year study period. The median duration until development of CKD in the OSA cohort was 3.2 years, 2.5 months earlier than that in the non OSA cohort. After exclusion of hypertension and diabetes, 4319 OSA patients was identified and the hazard ratio (HR) of CKD with OSA was 1.37 (95 % confidence interval [CI], 1.05-1.77; p = 0.019). In the subgroup analysis, an increased incidence of CKD in OSA was observed in women (HR, 1.41; 95 % CI, 1.12-1.78; p = 0.0036). CONCLUSIONS: This longitudinal population-based cohort study provides evidence that patients with OSA even without diabetes or hypertension are at higher risk of developing CKD over the next 3 years and nearly 2.5 months earlier than the non-OSA cohort, particularly women. PMID- 27380034 TI - Obstructive sleep apnea treated with custom-made bibloc and monobloc oral appliances: a retrospective comparative study. AB - PURPOSE: The primary purpose of this hypothesis-generating retrospective study was to compare the effect of monobloc and bibloc (NarvalTM) appliances on the apnea-hypopnea index (AHI) and the total cost of treatment during the first year of treatment. METHODS: Obstructive sleep apnea (OSA) subjects treated with a monobloc or bibloc during two different time periods were identified from medical records and data were extracted. Subjects treated with either of the appliances passed the same primary examination, follow-up visits, and follow-up polygraphic examination. A 1-year clinical follow-up was made on the bibloc group. RESULTS: The study analysis included 110 monobloc- and 55 bibloc-treated subjects with baseline mean AHI of 23 and 22, respectively. AHI responders (AHI < 10 and/or a >=50 % reduction of baseline AHI) were seen at follow-up in 61 % of the monobloc group and 56 % of the bibloc group. The improvement of the AHI value was similar in the two groups, with mean declines of 12.7 and 13.8, respectively. The ODI (oxygen desaturation index), lowest SpO2, longest apnea, and the mean Epworth sleepiness scale (ESS) score were significantly reduced by 3.1 (monobloc) and 2.2 (bibloc), i.e., at the same level for both groups. The total direct cost of treatment for a 1-year treatment was 17 % higher for the bibloc-treated subjects than for the monobloc-treated subjects. CONCLUSIONS: The results indicate that the monobloc and bibloc appliances are equally effective but the cost of treatment over 1 year was higher with the bibloc. However, prospective randomized controlled trials are needed to adequately test the assumption that the two treatment modalities are equally effective. PMID- 27380035 TI - Developing Bisexual Attract-and-Kill for Polyphagous Insects: Ecological Rationale versus Pragmatics. AB - We discuss the principles of bisexual attract-and-kill, in which females as well as males are targeted with an attractant, such as a blend of plant volatiles, combined with a toxicant. While the advantages of this strategy have been apparent for over a century, there are few products available to farmers for inclusion in integrated pest management schemes. We describe the development, registration, and commercialization of one such product, Magnet((r)), which was targeted against Helicoverpa armigera and H. punctigera in Australian cotton. We advocate an empirical rather than theoretical approach to selecting and blending plant volatiles for such products, and emphasise the importance of field studies on ecologically realistic scales of time and space. The properties required of insecticide partners also are discussed. We describe the studies that were necessary to provide data for registration of the Magnet((r)) product. These included evidence of efficacy, including local and area-wide impacts on the target pest, non-target impacts, and safety for consumers and applicators. In the decade required for commercial development, the target market for Magnet((r)) has been greatly reduced by the widespread adoption of transgenic insect-resistant cotton in Australia. We discuss potential applications in resistance management for transgenic cotton, and for other pests in cotton and other crops. PMID- 27380037 TI - [Not Available]. PMID- 27380036 TI - Insect Adhesion Secretions: Similarities and Dissimilarities in Hydrocarbon Profiles of Tarsi and Corresponding Tibiae. AB - Spatially controlled in vivo sampling by contact solid phase microextraction with a non-coated silica fiber combined with gas chromatography-mass spectrometry (GC MS) was utilized for hydrocarbon profiling in tarsal adhesion secretions of four insect species (Nicrophorus vespilloides, Nicrophorus nepalensis, Sagra femorata, and Gromphadorhina portentosa) by using distinct adhesion systems, viz. hairy or smooth tarsi. For comparison, corresponding samples from tibiae, representing the general cuticular hydrocarbon profile, were analyzed to enable the statistical inference of active molecular adhesion principles in tarsal secretions possibly contributed by specific hydrocarbons. n-Alkanes, monomethyl and dimethyl alkanes, alkenes, alkadienes, and one aldehyde were detected. Multivariate statistical analysis (principal component and orthogonal partial least square discriminant analyses) gave insights into distinctive molecular features among the various insect species and between tarsus and tibia samples. In general, corresponding hydrocarbon profiles in tarsus and tibia samples largely resembled each other, both qualitatively and in relative abundances as well. However, several specific hydrocarbons showed significantly different relative abundances between corresponding tarsus and tibia samples, thus indicating that such differences of specific hydrocarbons in the complex mixtures might constitute a delicate mechanism for fine-tuning the reversible attachment performances in tarsal adhesive fluids that are composed of substances originating from the same pool as cuticular hydrocarbons. Caused by melting point depression, the multicomponent tarsal adhesion secretion, made up of straight chain alkanes, methyl alkanes, and alkenes will have a semi-solid, grease-like consistency, which might provide the basis for a good reversible attachment performance. PMID- 27380038 TI - 5-LOX Inhibitor Zileuton Reduces Inflammatory Reaction and Ischemic Brain Damage Through the Activation of PI3K/Akt Signaling Pathway. AB - Previous studies from our laboratories showed that an anti-inflammatory drug, 5 lipoxygenase inhibitor zileuton, attenuates ischemic brain damage via inhibiting inflammatory reaction. However, it was elusive whether zileuton attenuates inflammatory reaction and ischemic brain damage through the modulation of PI3K/Akt signaling pathway. In the present study, we, for the first time, investigated whether PI3K/Akt pathway was involved in zileuton's anti inflammatory and neuroprotective properties against brain damage following experimental ischemic stroke. Adult male Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO), then received treatment with zileuton or vehicle after the onset of ischemia. LY294002 was injected intracerebroventricularly to inhibit the activation of PI3K/Akt signaling pathway selectively. Neurological deficit scores, cerebral infarct volume, morphological characteristic and cerebral water content were assessed 24 h after cerebral ischemia. The enzymatic activity of myeloperoxidase (MPO) was measured 24 h after cerebral ischemia. Expression of p-Akt, t-Akt and COX-2 in ischemic brain were determined by western blot. NF-kappaB p65 immuno-positive cells in ischemic brain were detected 24 h after cerebral ischemia. The content of TNF-alpha in blood was examined by ELISA. 5-LOX inhibitor zileuton significantly reduces neurological deficit scores, cerebral infarct volume, cerebral water content, ischemic neuronal injury and the enzymatic activity of MPO, all of which were abolished by LY294002 administration. Zileuton significantly up-regulates the expression of p Akt, which was inhibited by LY294002 administration. Zileuton significantly down regulates the over-expression of NF-kappaB p65 and COX-2, and attenuates the release of TNF-alpha, all of which were disminished by LY294002 administration. These results suggest that zileuton attenuates ischemic brain damage by inhibiting inflammatory reaction through the activation of PI3K/Akt signaling pathway. PMID- 27380039 TI - Use of 3D pseudo-continuous arterial spin labeling to characterize sex and age differences in cerebral blood flow. AB - INTRODUCTION: The aim of the present study is to use 3D pseudo-continuous arterial spin labeling (pCASL) to measure changes in normal cerebral blood flow (CBF) values with sex and age. METHODS: Eighty subjects underwent magnetic resonance imaging study on a 3.0-T scanner. 3D pCASL was used to measure CBF. Estradiol and testosterone levels were also assessed. Based on sex and age, the subjects were divided into four groups for statistical analysis. RESULTS: CBF was higher in young premenopausal women than in young men (P < 0.01), while there was no difference in CBF between older postmenopausal women and older men. CBF was also significantly decreased in older postmenopausal women compared with young women (P < 0.01), whereas no such age-related effect was present in men. CONCLUSION: These observations indicate that sex and age differences are important considerations when studying nervous system diseases and that the age range and female-to-male ratio should be considered in the selection of subjects for brain studies in order to eliminate bias. Further, the normal CBF values assessed by pCASL provide a basis for further clinical use of pCASL. PMID- 27380040 TI - Comparison of automated brain volumetry methods with stereology in children aged 2 to 3 years. AB - INTRODUCTION: The accurate and precise measurement of brain volumes in young children is important for early identification of children with reduced brain volumes and an increased risk for neurodevelopmental impairment. Brain volumes can be measured from cerebral MRI (cMRI), but most neuroimaging tools used for cerebral segmentation and volumetry were developed for use in adults and have not been validated in infants or young children. Here, we investigate the feasibility and accuracy of three automated software methods (i.e., SPM, FSL, and FreeSurfer) for brain volumetry in young children and compare the measures with corresponding volumes obtained using the Cavalieri method of modern design stereology. METHODS: Cerebral MRI data were collected from 21 children with a complex congenital heart disease (CHD) before Fontan procedure, at a median age of 27 months (range 20.9 42.4 months). Data were segmented with SPM, FSL, and FreeSurfer, and total intracranial volume (ICV) and total brain volume (TBV) were compared with corresponding measures obtained using the Cavalieri method. RESULTS: Agreement between the estimated brain volumes (ICV and TBV) relative to the gold standard stereological volumes was strongest for FreeSurfer (p < 0.001) and moderate for SPM segment (ICV p = 0.05; TBV p = 0.006). No significant association was evident between ICV and TBV obtained using SPM NewSegment and FSL FAST and the corresponding stereological volumes. CONCLUSIONS: FreeSurfer provides an accurate method for measuring brain volumes in young children, even in the presence of structural brain abnormalities. PMID- 27380041 TI - Software output from semi-automated planimetry can underestimate intracerebral haemorrhage and peri-haematomal oedema volumes by up to 41. AB - INTRODUCTION: Haematoma and oedema size determines outcome after intracerebral haemorrhage (ICH), with each added 10 % volume increasing mortality by 5 %. We assessed the reliability of semi-automated computed tomography planimetry using Analyze and Osirix softwares. METHODS: We randomly selected 100 scans from 1329 ICH patients from two centres. We used Hounsfield Unit thresholds of 5-33 for oedema and 44-100 for ICH. Three raters segmented all scans using both softwares and 20 scans repeated for intra-rater reliability and segmentation timing. Volumes reported by Analyze and Osirix were compared to volume estimates calculated using the best practice method, taking effective individual slice thickness, i.e. voxel depth, into account. RESULTS: There was excellent overall inter-rater, intra-rater and inter-software reliability, all intraclass correlation coefficients >0.918. Analyze and Osirix produced similar haematoma (mean difference: Analyze - Osirix = 1.5 +/- 5.2 mL, 6 %, p <= 0.001) and oedema volumes (-0.6 +/- 12.6 mL, -3 %, p = 0.377). Compared to a best practice approach to volume calculation, the automated haematoma volume output was 2.6 mL (-11 %) too small with Analyze and 4.0 mL (-18 %) too small with Osirix, whilst the oedema volumes were 2.5 mL (-12 %) and 5.5 mL (-25 %) too small, correspondingly. In scans with variable slice thickness, the volume underestimations were larger, 29%/-36 % for ICH and -29 %/-41 % for oedema. Mean segmentation times were 6:53 +/- 4:02 min with Analyze and 9:06 +/- 5:24 min with Osirix (p < 0.001). CONCLUSION: Our results demonstrate that the method used to determine voxel depth can influence the final volume output markedly. Results of clinical and collaborative studies need to be considered in the context of these methodological differences. PMID- 27380042 TI - Impact of patient age on the iodine/FDG "flip-flop" phenomenon in lung metastasis from thyroid cancer. AB - OBJECTIVES: Radioiodine therapy is an effective treatment for lung metastasis from thyroid cancer. However, cases of lung metastasis without iodine uptake are often encountered. In such cases, FDG accumulation in lung lesions is often observed. There is a reverse relationship between iodine and FDG accumulation in thyroid cancer lesions, the so-called "flip-flop" phenomenon. The aim of this study was to assess the relationship between patient age and the occurrence of the flip-flop phenomenon. METHODS: Eighty-six patients who underwent radioiodine therapy for lung metastasis were studied retrospectively (age 17-73 years; median 60 years; males:females 22:64). We compared the clinical data and imaging findings (size and FDG uptake of lung nodules) between patients with (n = 44) and without (n = 42) iodine uptake in lung metastasis. RESULTS: Significantly more young patients showed iodine accumulation in lung metastasis than old patients (p = 0.0025). Lung metastases with larger size or greater FDG uptake showed no iodine uptake more frequently with significant difference (p = 0.015 and <0.001, respectively). Among patients with FDG uptake in the lung metastasis, 57.1 % of young patients (<60 years) and 24.3 % of the old patients (>=60 years) showed iodine uptake (p = 0.0029). CONCLUSIONS: Higher patient age and lung nodules with large size or FDG accumulation are negative factors for iodine accumulation in lung metastases from thyroid cancer. In addition, our results show that young patients have a greater likelihood of iodine uptake even when FDG accumulates in lung metastasis, in contrast to old patients. PMID- 27380043 TI - Tetramethylpyrazine Protects Against Oxygen-Glucose Deprivation-Induced Brain Microvascular Endothelial Cells Injury via Rho/Rho-kinase Signaling Pathway. AB - Tetramethylpyrazine (TMP, also known as Ligustrazine), which is isolated from Chinese Herb Medicine Ligustium wollichii Franchat (Chuan Xiong), has been widely used in China for the treatment of ischemic stroke by Chinese herbalists. Brain microvascular endothelial cells (BMECs) are the integral parts of the blood-brain barrier (BBB), protecting BMECs against oxygen-glucose deprivation (OGD) which is important for the treatment of ischemic stroke. Here, we investigated the protective mechanisms of TMP, focusing on OGD-injured BMECs and the Rho/Rho kinase (Rho-associated kinases, ROCK) signaling pathway. The model of OGD-injured BMECs was established in this study. BMECs were identified by von Willebrand factor III staining and exposed to fasudil, or TMP at different concentrations (14.3, 28.6, 57.3 uM) for 2 h before 24 h of OGD injury. The effect of each treatment was examined by cell viability assays, measurement of intracellular reactive oxygen species (ROS), and transendothelial electric resistance and western blot analysis (caspase-3, endothelial nitric oxide synthase (eNOS), RhoA, Rac1). Our results show that TMP significantly attenuated apoptosis and the permeability of BMECs induced by OGD. In addition, TMP could notably down regulate the characteristic proteins in Rho/ROCK signaling pathway such as RhoA and Rac1, which triggered abnormal changes of eNOS and ROS, respectively. Altogether, our results show that TMP has a strong protective effect against OGD induced BMECs injury and suggest that the mechanism might be related to the inhibition of the Rho/ROCK signaling pathway. PMID- 27380045 TI - Intraoperative neurophysiologic monitoring: utility and anesthetic implications. AB - PURPOSE OF REVIEW: Intraoperative neurophysiologic monitoring (IONM) has been rapidly adopted as a standard monitoring technique for a growing number of surgical procedures. This article offers a basic review of IONM and discusses some of its latest applications and anesthetic techniques that optimize monitoring conditions. RECENT FINDINGS: IONM has been demonstrated to alert the surgical team to potential injury and can also be used to detect impending positioning injuries. Upper extremity somatosensory evoked potential monitoring is particularly helpful in preventing ulnar neuropathy that is more common in patients who are positioned prone and with severe arm abduction. Somatosensory evoked potential monitoring has a high specificity for vascular compromise and neurologic ischemia that may occur during neurovascular procedures. Electroencephalography is also helpful in alerting the surgical and anesthesia teams to an impending ischemic event. Although a total intravenous anesthesia technique offers better monitoring conditions, propofol may prolong emergence. SUMMARY: IONM is commonly used in a growing number and variety of surgical procedures, and has been shown to improve outcomes. IONM poses challenges for the anesthesiologist, but tailoring the anesthetic to be compatible with the monitoring techniques in use can help to prevent surgical complications. PMID- 27380046 TI - What is the OPTiMal Way to Manage In-Transit Disease? PMID- 27380044 TI - Involvement of Spinal PKMzeta Expression and Phosphorylation in Remifentanil Induced Long-Term Hyperalgesia in Rats. AB - Up-regulation of GluN2B-containing N-methyl-D-aspartate receptors (NMDARs) expression and trafficking is the key mechanism for remifentanil-induced hyperalgesia (RIH), nevertheless, the signaling pathway and pivotal proteins involved in RIH remain equivocal. PKMzeta, an isoform of protein kinase C (PKC), maintains pain memory storage in neuropathic pain and inflammatory pain, which plays a parallel role regulated by NMDARs in long-term memory trace. In the present study, Zeta Inhibitory Peptide (ZIP), a PKMzeta inhibitor, and a selective GluN2B antagonist Ro-256981 are injected intrathecally before remifentanil infusion (1 MUg kg-1 min-1 for 1 h, iv) in order to detect whether GluN2B contributes to RIH through affecting synthesis and activity of PKMzeta in spinal dorsal horn. Nociceptive tests are measured by Paw withdrawal mechanical threshold (PWT) and paw withdrawal thermal latency (PWL). The L4-L6 segments of dorsal horn taken from rats with RIH are for determining expression of PKMzeta and pPKMzeta by Western blot and immunohistochemistry. Our data suggest that remifentanil infusion causes an increase of PKMzeta in expression and phosphorylation in rats with nociceptive sensitization, beginning at 2 h, peaked at 2 days, and returned to basal level at 7 days. ZIP (10 ng) could block behavioral sensitization induced by remifentanil. Ro25-6981 dosage-dependently attenuated mechanical and thermal hyperalgesia and reversed expression of PKMzeta and pPKMzeta, indicating that GluN2B-containing NMDA receptor facilitates development of RIH through mediating expression and activity of spinal PKMzeta in rats. Although detailed mechanisms require further comprehensive study, the preventive role of Ro25-6981 and ZIP provide novel options for the effective precaution of RIH in clinics. PMID- 27380047 TI - Predictors of Treatment Decisions in Multidisciplinary Oncology Meetings: A Quantitative Observational Study. AB - BACKGROUND: In many healthcare systems, treatment recommendations for cancer patients are formulated by multidisciplinary tumor boards (MTBs). Evidence suggests that interdisciplinary contributions to case reviews in the meetings are unequal and information-sharing suboptimal, with biomedical information dominating over information on patient comorbidities and psychosocial factors. This study aimed to evaluate how different elements of the decision process affect the teams' ability to reach a decision on first case review. METHODS: This was an observational quantitative assessment of 1045 case reviews from 2010 to 2014 in cancer MTBs using a validated tool, the Metric for the Observation of Decision-making. This tool allows evaluation of the quality of information presentation (case history, radiological, pathological, and psychosocial information, comorbidities, and patient views), and contribution to discussion by individual core specialties (surgeons, oncologists, radiologists, pathologists, and specialist cancer nurses). The teams' ability to reach a decision was a dichotomous outcome variable (yes/no). RESULTS: Using multiple logistic regression analysis, the significant positive predictors of the teams' ability to reach a decision were patient psychosocial information (odds ratio [OR] 1.35) and the inputs of surgeons (OR 1.62), radiologists (OR 1.48), pathologists (OR 1.23), and oncologists (OR 1.13). The significant negative predictors were patient comorbidity information (OR 0.83) and nursing inputs (OR 0.87). CONCLUSIONS: Multidisciplinary inputs into case reviews and patient psychosocial information stimulate decision making, thereby reinforcing the role of MTBs in cancer care in processing such information. Information on patients' comorbidities, as well as nursing inputs, make decision making harder, possibly indicating that a case is complex and requires more detailed review. Research should further define case complexity and determine ways to better integrate patient psychosocial information into decision making. PMID- 27380048 TI - [Intern(euron)al affairs : The role of specific neocortical interneuron classes in the interaction between acetylcholine and GABAergic anesthetics]. AB - Acetylcholine is a neuromodulator which is released throughout the central nervous system and plays an essential role in consciousness and cognitive processes including attention and learning. Due to its 'activating' effect on the neuronal and behavioral level its interaction with anesthetics has long been of interest to anesthesiologists. It is widely held that a reduction of the release of acetylcholine by general anesthetics constitutes part of the anesthetic effect. This notion is backed by numerous human and animal studies, but is also in seeming contradiction to findings that acetylcholine activates specific classes of inhibitory neurons: if acetylcholine excites elements within the neuronal network responsible for the release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), its withdrawal should diminish, not enhance, the effect of anesthetics.Focusing on cortical circuits, we present an overview of recent advances in cellular neurophysiology, particularly the interactions between inhibitory neuron classes, which provide insights on the interaction between acetylcholine and GABA. PMID- 27380049 TI - Randomized crossover study assessing oropharyngeal leak pressure and fiber optic positioning : Laryngeal Mask Airway SupremeTM versus Laryngeal Tube LTS IITM size 2 in non-paralyzed anesthetized children. AB - BACKGROUND: As there are currently no data available comparing the practicability of the laryngeal mask airway (LMA) SupremeTM size 2 versus the laryngeal tube LTS IITM size 2 in children, this trial was conducted to quantify the differences between these two airway devices concerning leak pressure and fiber optic controlled positioning in non-paralyzed, anesthetized pediatric patients. METHODS: A total of 56 children aged 1-6 years and weighing between 11 and 23 kg were enrolled in the study. Anesthesia was intravenously induced according to local standards using fentanyl and propofol. After induction of anesthesia both airway devices were inserted consecutively in accordance with the randomization protocol. RESULTS: The mean oropharyngeal leak pressure was significantly higher for the LTS IITM (33+/-8 cmH2O) than for the LMA SupremeTM (21+/-7 cmH2O, p < 0.0001). Fiber optic position monitoring was better when the LMA SupremeTM was used (p < 0.001). The first attempt success rates for insertion (55Supreme LMA vs. 43LTSII, p < 0.001), the insertion time (25 s Supreme LMA vs. 34 s LTSII, p < 0.04) and the frequency of bloodstaining (0Supreme LMA vs 4LTSII, p < 0.04) for the initially used device were better for the LMA SupremeTM than the laryngeal tube LTS IITM. CONCLUSION: We conclude that oropharyngeal leak pressure, fiber optic position, first attempt insertion success rate and bloodstaining differed between the LMA SupremeTM and the LTS IITM in children. PMID- 27380050 TI - [Performance development of a university operating room after implementation of a central operating room management]. AB - The difficult financial situation in German hospitals requires measures for improvement in process quality. Associated increases in revenues in the high income field "operating room (OR) area" are increasingly the responsibility of OR management but it has not been shown that the introduction of an efficiency oriented management leads to an increase in process quality and revenues in the operating theatre. Therefore the performance in the operating theatre of the University Medical Center Gottingen was analyzed for working days in the core operating time from 7.45 a.m. to 3.30 p.m. from 2009 to 2014. The achievement of process target times for the morning surgery start time and the turnover times of anesthesia and OR-nurses were calculated as indicators of process quality. The number of operations and cumulative incision-suture time were also analyzed as aggregated performance indicators. In order to assess the development of revenues in the operating theatre, the revenues from diagnosis-related groups (DRG) in all inpatient and occupational accident cases, adjusted for the regional basic case value from 2009, were calculated for each year. The development of revenues was also analyzed after deduction of revenues resulting from altered economic case weighting. It could be shown that the achievement of process target values for the morning surgery start time could be improved by 40 %, the turnover times for anesthesia reduced by 50 % and for the OR-nurses by 36 %. Together with the introduction of central planning for reallocation, an increase in operation numbers of 21 % and cumulative incision-suture times of 12% could be realized. Due to these additional operations the DRG revenues in 2014 could be increased to 132 % compared to 2009 or 127 % if the revenues caused by economic case weighting were excluded. The personnel complement in anesthesia (-1.7 %) and OR-nurses (+2.6 %) as well as anesthetists (+6.7 %) increased less compared to the revenues or were slightly reduced. This improvement in process quality and cumulative incision-suture times as well as the increase in revenues, reflect the positive impact of an efficiency-oriented central OR management. The OR management releases due to measures of process optimization the necessary personnel and time resources and therefore achieves the basic prerequisites for increased revenues of surgical disciplines. The method presented can be used by other hospitals as a guideline to analyze performance development. PMID- 27380053 TI - [Not Available]. PMID- 27380051 TI - [Perioperative coagulation management during ascending aorta replacement on apixaban]. AB - The direct oral anticoagulants (DOACs) present a valid therapeutic alternative to vitamin K antagonists in patients with non-valvular atrial fibrillation, for the prevention of venous thromboembolism, and for the treatment and prevention of the recurrence of pulmonary embolisms and deep vein thrombosis. Despite Idarucizumab as an antagonist of Dabigatran there are no other specific antidotes available yet. Therefore, perioperative coagulation management by DOACs is challenging in patients undergoing emergency surgical procedures with a high risk of bleeding complications. This case study describes the perioperative procedure during ascending aorta replacement after aortic dissection with apixaban administration. PMID- 27380052 TI - Synthesis, characterization, and biological studies of diosgenyl analogs. AB - A series of diosgenyl analogs were prepared from diosgenin to evaluate their anticancer activity and antithrombotic property. Analog 4, which had a spiroketal structure with a 6-aminohexanoic acid residue, exhibited the highest potency against all five tumor cell lines. It significantly blocked tumor growth, induced cell apoptosis and autophagy, and regulated cellular calcium concentration, mitochondrial membrane potential, adenosine triphosphate, and cell cycle. In addition, fluorescence-tagged compounds indicated that the analogs could rapidly accumulate in the cytoplasm, but no specific localization in the nucleus of cancer cells was observed. Furthermore, preliminary structure-activity relationship studies demonstrated that spiroketal analogs exhibit better antithrombotic activity than furostanic analogs, which exhibit the opposite effect by promoting thrombosis. Our study indicates that compound 4 may be a promising anticancer drug candidate for cancer patients with thromboembolism. PMID- 27380055 TI - Glycemic control, compliance, and satisfaction for diabetic gravidas in centering group care. AB - PURPOSE: To determine if diabetic gravidas enrolled in Centering(r) group care have improved glycemic control compared to those attending standard prenatal care. To compare compliance and patient satisfaction between the groups. MATERIALS AND METHODS: We conducted a prospective cohort study of diabetics enrolled in centering group care from October 2013 to December 2015. Glycemic control, compliance and patient satisfaction (five-point Likert scale) were evaluated. Student's t-test, Chi-Square and mixed effects model were used to compare outcomes. RESULTS: We compared 20 patients in centering to 28 standard prenatal care controls. Mean fasting blood sugar was lower with centering group care (91.0 versus 105.5 mg/dL, p =0.017). There was no difference in change in fasting blood sugar over time between the two groups (p = 0.458). The percentage of time patients brought their blood glucose logs did not differ between the centering group and standard prenatal care (70.7 versus 73.9%, p = 0.973). Women in centering group care had better patient satisfaction scores for "ability to be seen by a physician" (5 versus 4, p = 0.041) and "time in waiting room" (5 versus 4, p =0.001). CONCLUSION: Fasting blood sugar was lower for patients in centering group care. Change in blood sugar over time did not differ between groups. Diabetic gravidas enrolled in centering group care report improved patient satisfaction. PMID- 27380056 TI - Role of long non-coding RNA in tumor drug resistance. AB - Chemotherapy has been extensively used in tumor treatment, including either systemic or local treatment. Miserably, in many kinds of cancers, chemotherapy is gradually insensitive. The mechanisms of tumor drug resistance have been widely explored, yet have not been fully characterized. With several studies in the development of drug resistance, recent works have highlighted the involvement of non-coding RNAs in tumor development. A growing number of long non-coding RNAs (lncRNAs) have been identified as transcripts of larger than 200 nucleotides in length, which have low coding potential, but potentially coding small peptides with 50-70 amino acids. Despite so often being branded as transcriptional noise, it is becoming increasingly clear that a large number of lncRNAs are crucial molecular regulators of the processes of tumor involving the initiation and progression of human tumor. More recently, accumulating evidence is revealing an important role of lncRNA in tumor drug resistance and lncRNA expression profiling can be correlated with the evolution of tumor drug resistance. The long non coding-RNA-mediated form of drug resistance brings yet another mechanism of drug resistance. So, exploiting the newly emerging knowledge of lncRNAs for the development of new therapeutic applications to overcome human tumor drug resistance will be significant. PMID- 27380058 TI - Diagnosis and Treatment of Pediatric Necrotizing Fasciitis: A Systematic Review of the Literature. AB - Introduction Pediatric necrotizing fasciitis (NF) is a rare but severe, life threatening infection. Early diagnosis is crucial to reduce morbidity and mortality, but initial symptoms are nonspecific. Little sound data exists on factors aiding clinicians to recognize NF in children. With a systematic literature review, we aimed to better characterize pediatric NF. We focused on triggers, symptoms, and laboratory and microbiological findings and differences between pediatric adult patients. Materials and Methods A literature research was conducted according to the guidance of the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses." Articles published between January 2010 and October 2015 were included. Data extraction was performed as an iterative process. Results A total of 32 articles describing 53 pediatric patients with NF were included in the analysis. Overall mortality was 15.4%. Frequency peaks were found for neonates and children aged between 1 and 2 years. These two age groups were predominantly affected on the torso. Another frequency peak was found in patients aged around 10 years of age. These patients were predominantly affected on the extremities and face. In general, early symptoms were found to be fever, erythema, localized selling, and tenderness or pain. "Pain out of proportion" was not mentioned as a typical symptom. Fever and leukocytosis were more common in teenage patients. Monomicrobial necrotizing (type 2) fasciitis was much more common than polymicrobial (type 1) fasciitis. Next to Streptococci and Staphylococci, Pseudomonas aeruginosa was often isolated. Early aggressive surgical treatment was the treatment of choice. Conclusions Pediatric NF has distinguishing features that differ from adult NF. Knowledge of these details should increase early diagnosis and improve treatment. PMID- 27380057 TI - GPC-HCC model: a combination of glybican-3 with other routine parameters improves the diagnostic efficacy in hepatocellular carcinoma. AB - Conflicting results for circulating glypican-3 (GPC3) were reported in hepatocellular carcinoma (HCC) diagnosis. We aimed to improve the diagnostic power of GPC3 by developing a GPC-HCC model for diagnosing HCC. GPC3 was tested for HCC (138), liver cirrhosis (56), and fibrosis (62) patients by ELISA. Data from patient groups were retrospectively analyzed. A novel score, GPC-HCC, based on combination of GPC3 and routine laboratory tests, was developed for HCC diagnosis. The GPC-HCC model values produced a significant 1.7-fold increase in liver cirrhosis and 3.2-fold increase in HCC, in comparison with liver fibrosis. In contrast to GPC3 and alpha fetoprotein (AFP), the GPC-HCC model showed high HCC diagnostic power with area under the curve (AUC) of 0.939, sensitivity 93 %, specificity 93 %, positive predictive value 89 %, negative predictive value 95 %, and efficiency 93 %. GPC-HCC AUC in HCC with single tumor, absent vascular invasion, and tumor size <=3 cm were 0.93, 0.92, and 0.92, respectively, compared with 0.63, 0.63, and 0.64, respectively, for GPC3 and 0.69, 0.70, 0.55, respectively, for AFP. In conclusion, owing to these promising findings, the combination of GPC3 with other laboratory simple routine tests (GPC-HCC model) could improve the diagnostic power of GPC3 in HCC screening and follow up of cirrhotic patients. PMID- 27380059 TI - Nutritional and Environmental Effects on Ammonia Emissions from Dairy Cattle Housing: A Meta-Analysis. AB - Nitrogen excreted in dairy manure can be potentially transformed and emitted as NH, which can create livestock and human respiratory problems and be an indirect source of NO. The objectives of this study were to: (i) investigate environmental factors influencing NH emissions from dairy housing; and (ii) identify key explanatory variables in the NH emissions prediction from dairy housing using a meta-analytical approach. Data from 25 studies were used for the preliminary analysis, and data from 10 studies reporting 87 treatment means were used for the meta-analysis. Season and flooring type significantly affected NH emissions. For nutritional effect analysis, the between-study variability (heterogeneity) of mean NH emission was estimated using random-effect models and had a significant effect ( < 0.01). Therefore, random-effect models were extended to mixed-effect models to explain heterogeneity regarding the available dietary and animal variables. The final mixed-effect model included milk yield, dietary crude protein, and dry matter intake separately, explaining 45.5% of NH emissions heterogeneity. A unit increase in milk yield (kg d) resulted in a 4.9 g cow d reduction in NH emissions, and a unit increase in dietary crude protein content (%) and dry matter intake (kg d) resulted in 10.2 and 16.3 g cow d increases in NH emissions, respectively, in the scope of this study. These results can be further used to help identify mitigation strategies to reduce NH emissions from dairy housing by developing predictive models that could determine variables with strong association with NH emissions. PMID- 27380060 TI - Lower Nitrous Oxide Emissions from Anhydrous Ammonia Application Prior to Soil Freezing in Late Fall Than Spring Pre-Plant Application. AB - Fall application of anhydrous ammonia in Manitoba is common but its impact on nitrous oxide (NO) emissions is not well known. A 2-yr study compared application before freeze-up in late fall to spring pre-plant application of anhydrous ammonia on nitrous oxide (NO) emissions from a clay soil in the Red River Valley, Manitoba. Spring wheat ( L.) and corn ( L.) were grown on two 4-ha fields in 2011 and 2012, respectively. Field-scale flux of NO was measured using a flux-gradient micrometeorological approach. Late fall treatment did not induce NO emissions soon after application or in winter likely because soil was frozen. Application time did alter the temporal pattern of emissions with late fall and spring pre plant applications significantly increasing median daily NO flux at spring thaw and early crop growing season, respectively. The majority of emissions occurred in early growing season resulting in cumulative emissions for the crop year being numerically 33% less for late fall than spring pre-plant application. Poor yield in the first year with late fall treatment occurred because of weed and volunteer growth with delayed planting. Results show late fall application of anhydrous ammonia before freeze-up increased NO emissions at thaw and decreased emissions for the early growing season compared to spring pre-plant application. However, improved nitrogen availability of late fall application to crops the following year is required when planting is delayed because of excessive moisture in spring. PMID- 27380061 TI - Microbial Community and Chemical Characteristics of Swine Manure during Maturation. AB - Swine diet formulations have the potential to lower animal emissions, including odor and ammonia (NH). The purpose of this study was to determine the impact of manure storage duration on manure chemical and microbial properties in swine feeding trials. Three groups of 12 pigs were fed a standard corn-soybean meal diet over a 13-wk period. Urine and feces were collected at each feeding and transferred to 12 manure storage tanks. Manure chemical characteristics and headspace gas concentrations were monitored for NH, hydrogen sulfide (HS), volatile fatty acids, phenols, and indoles. Microbial analysis of the stored manure included plate counts, community structure (denaturing gradient gel electrophoresis), and metabolic function (Biolog). All odorants in manure and headspace gas concentrations were significantly ( < 0.01) correlated for length of storage using quadratic equations, peaking after Week 5 for all headspace gases and most manure chemical characteristics. Microbial community structure and metabolic utilization patterns showed continued change throughout the 13-wk trial. Denaturing gradient gel electrophoresis species diversity patterns declined significantly ( < 0.01) with time as substrate utilization declined for sugars and certain amino acids, but functionality increased in the utilization of short chain fatty acids as levels of these compounds increased in manure. Studies to assess the effect of swine diet formulations on manure emissions for odor need to be conducted for a minimum of 5 wk. Efforts to determine the impact of diets on greenhouse gas emissions will require longer periods of study (>13 wk). PMID- 27380062 TI - Greenhouse Gas Emissions from Septic Systems in New York State. AB - Onsite septic systems use microbial processes to eliminate organic wastes and nutrients such as nitrogen; these processes can contribute to air pollution through the release of greenhouse gases (GHGs). Current USEPA estimates for septic system GHG emissions are based on one study conducted in north-central California and are limited to methane; therefore, the contribution of these systems to the overall GHG emission budget is unclear. This study quantified and compared septic system GHG emissions from the soil over leach fields and the roof vent, which are the most likely locations for gas emissions during normal septic system operation. At each of eight septic systems, we measured fluxes of CH, CO, and NO using a static chamber method. The roof vent released the majority of septic system gas emissions. In addition, the leach field was a significant source of NO fluxes. Comparisons between leach field and vent emissions suggest that biological processes in the leach field soil may influence the type and quantity of gas released. Overall, our results suggest that (i) revisions are needed in USEPA guidance (e.g., septic systems are not currently listed as a source of NO emissions) and (ii) similar studies representing a wider range of climatic and geographic settings are needed. The total vent, sand filter, and leach field GHG emissions were 0.17, 0.045, and 0.050 t CO-equivalents capita yr, respectively. In total, this represents about 1.5% of the annual carbon footprint of an individual living in the United States. PMID- 27380063 TI - Distillers By-Product Cattle Diets Enhance Reduced Sulfur Gas Fluxes from Feedlot Soils and Manures. AB - Total reduced sulfur (TRS) emissions from animal feeding operations are a concern with increased feeding of high-sulfur distillers by-products. Three feeding trials were conducted to evaluate feeding wet distillers grain plus solubles (WDGS) on TRS fluxes. Fresh manure was collected three times during Feeding Trial 1 from cattle fed 0, 20, 40, and 60% WDGS. Fluxes of TRS from 40 and 60% WDGS manures were 3- to 13-fold greater than the 0 and 20% WDGS manures during the first two periods. In the final period, TRS flux from 60% WDGS was 5- to 22-fold greater than other WDGS manures. During Feeding Trial 2, 0 and 40% WDGS diets on four dates were compared in feedlot-scale pens. On two dates, fluxes from mixed manure and soil near the feed bunk were 3.5-fold greater from 40% WDGS pens. After removing animals, soil TRS flux decreased 82% over 19 d but remained 50% greater in 40% WDGS pens, principally from the wetter pen edges (1.9-fold greater than the drier central mound). During two cycles of cattle production in Feeding Trial 3, TRS soil fluxes were 0.3- to 4-fold greater over six dates for pens feeding WDGS compared with dry-rolled corn diet and principally from wetter pen edges. Soil TRS flux correlated with %WDGS, total N, total P, manure pack temperature, and surface temperature. Consistent results among these three trials indicate that TRS fluxes increase by two- to fivefold when cattle were fed greater levels of WDGS, but specific manure management practices may help control TRS fluxes. PMID- 27380064 TI - Nitrous Oxide Fluxes, Soil Oxygen, and Denitrification Potential of Urine- and Non-Urine-Treated Soil under Different Irrigation Frequencies. AB - Despite increased use of irrigation to improve forage quality and quantity for grazing cattle ( Linnaeus), there is a lack of data that assess how irrigation practices influence nitrous oxide (NO) emissions from urine-affected soils. Irrigation effects on soil oxygen (O) availability, a primary controller of NO fluxes, is poorly understood. It was hypothesized that increased irrigation frequency would result in lower NO emissions by increasing soil moisture and decreasing soil O concentrations. This would favor more NO reduction to dinitrogen (N). We examined effects of high (3-d) versus low (6-d) irrigation frequency with and without bovine urine addition to pasture. Nitrous oxide fluxes were measured daily for 35 d. Soil O, temperature, and water content were continuously measured at multiple depths. Inorganic nitrogen, organic carbon, and soil pH were measured at 6-d intervals. Measurements of denitrification enzyme activity with and without acetylene inhibition were used to infer the NO/(NO + N) ratio. The NO/(NO + N) ratio was lower under high- compared with low-frequency irrigation, suggesting greater potential for NO reduction to N with more frequent irrigation. Although NO fluxes were increased by urine addition, they were not affected by irrigation frequency. Soil O decreased temporarily after urine deposition, but O dynamics did not explain NO dynamics. Relative soil gas diffusivity (/) was a better predictor of NO fluxes than O concentration. On a free-draining soil, increasing irrigation frequency while providing the same total water volume did not enhance NO emissions under ruminant urine patches in a grazed pasture. PMID- 27380065 TI - Ammonia Emission from a Beef Cattle Feedlot and Its Local Dry Deposition and Re Emission. AB - Ammonia (NH) volatized from livestock manure is affiliated with ecosystem and human health concerns and decreased fertilizer value of manure and can also be an indirect source of greenhouse gas. Beef cattle feedlots, where thousands of cattle are grouped together to enable greater control of feed management and production, are hot spots in the agricultural landscape for NH emissions. Quantifying the feedlot NH emissions is a difficult task, partly due to the reactive nature of NH within and surrounding the feedlot. Our study used a dispersion model coupled to field measurements to derive NH emissions from a feedlot in southern Alberta, Canada. The average feedlot NH emission was 50 MUg m s (85 g animal d), which coincides with a low dietary crude protein content. At a location 165 m east of the feedlot, a flux gradient (FG) technique measured an average NH deposition of 12.0 MUg m s (west wind) and 5.3 MUg m s (east wind). Ammonia FG emission averaged 1 MUg m s with east winds, whereas no NH emission was found for west wind. Using soil-captured NH, there was a decrease in deposition with distance from the feedlot (50% over 200 m). Collectively, the results of this study provide insight into the dynamics of NH in the agricultural landscape and illustrate the need for NH mitigation to improve the environmental and economic sustainability of cattle feedlots. PMID- 27380066 TI - Evaluation of Intensive "4R" Strategies for Decreasing Nitrous Oxide Emissions and Nitrogen Surplus in Rainfed Corn. AB - The "4R" approach of using the right rate, right source, right timing, and right placement is an accepted framework for increasing crop N use efficiency. However, modifying only one 4R component does not consistently reduce nitrous oxide (NO) emissions. Our objective was to determine if N fertilizer applied in three split applications (Sp), by itself or combined with changes in N source and rate, could improve N recovery efficiency (NRE) and N surplus (NS) and decrease NO emissions. Over two corn ( L.) growing seasons in Minnesota, NO emissions ranged from 0.6 to 0.9 kg N ha. None of the treatment combinations affected grain yield. Compared with urea applied in a single application at the recommended N rate, Sp by itself did not improve NRE or NS and did not decrease NO. Combining Sp with urease and nitrification inhibitors and/or a 15% reduction in N rate increased NRE from 57 to >73% and decreased NS by >20 kg N ha. The only treatment that decreased NO (by 20-53%) was Sp combined with inhibitors and reduced N rate. Emissions of NO were more strongly correlated with NS calculated from grain N uptake ( = 0.61) compared with whole-plant N uptake ( = 0.39), possibly because most N losses occurred before grain filling. Optimizing both application timing and N source can allow for a moderate reduction in N rate that does not affect grain yield but decreases NO. Grain-based NS may be a more useful indicator of NO emissions than whole-plant-based NS. PMID- 27380067 TI - Standard Extraction Methods May Underestimate Nitrate Stocks Captured by Field Aged Biochar. AB - Biochar (BC) has been shown to increase the potential for N retention in agricultural soils. However, the form of N retained and its strength of retention are poorly understood. Here, we examined if the N retained could be readily extractable by standard methods and if the amount of N retained varied with BC field ageing. We investigated soil and field-aged BC (BC) particles of a field experiment (sandy soil amended with BC at 0, 15, and 30 t ha) under two watering regimes (irrigated and rain-fed). Throughout the study, greater nitrate than ammonium retention was observed with BC addition in topsoil (0-15 cm). Subsoil (15-30 cm) nitrate concentrations were reduced in BC treatments, indicating reduced nitrate leaching (standard 2 mol L KCl method). The mineral-N release of picked BC particles was examined with different methods: standard 2 mol L KCl extraction; repeated (10*) extraction in 2 mol L KCl at 22 +/- 2 degrees C and 80 degrees C (M); electro-ultrafiltration (M); repeated water + KCl long-term shaking (M); and M plus one repeated shaking at 80 degrees C (M). Nitrate amounts captured by BC particles were several-fold greater than those in the BC-amended soil. Compared with M, standard 2 mol L KCl or electro-ultrafiltration extractions retrieved only 13 and 30% of the total extractable nitrates, respectively. Our results suggest that "nitrate capture" by BC may reduce nitrate leaching in the field and that the inefficiency of standard extraction methods deserves closer research attention to decipher mechanisms for reactive N management. PMID- 27380068 TI - QMRAcatch: Human-Associated Fecal Pollution and Infection Risk Modeling for a River/Floodplain Environment. AB - Protection of drinking water resources requires addressing all relevant fecal pollution sources in the considered catchment. A freely available simulation tool, QMRAcatch, was recently developed to simulate concentrations of fecal indicators, a genetic microbial source tracking (MST) marker, and intestinal pathogens in water resources and to conduct a quantitative microbial risk assessment (QMRA). At the same time, QMRAcatch was successfully applied to a region of the Danube River in Austria, focusing on municipal wastewater emissions. Herein, we describe extension of its application to a Danube River floodplain, keeping the focus on fecal sources of human origin. QMRAcatch was calibrated to match measured human-associated MST marker concentrations for a dry year and a wet year. Appropriate performance characteristics of the human associated MST assay were proven by simulating correct and false-positive marker concentrations, as determined in human and animal feces. With the calibrated tool, simulated and measured enterovirus concentrations in the rivers were compared. Finally, the calibrated tool allowed demonstrating that 4.5 log enterovirus and 6.6 log norovirus reductions must be achieved to convert current surface water to safe drinking water that complies with a health-based target of 10 infections person yr. Simulations of the low- and high-pollution scenarios showed that the required viral reductions ranged from 0 to 8 log. This study has implications for water managers with interests in assessing robust catchment protection measures and water treatment criteria by considering the fate of fecal pollution from its sources to the point of abstraction. PMID- 27380069 TI - Improved Simulation of Edaphic and Manure Phosphorus Loss in SWAT. AB - Watershed models such as the Soil Water Assessment Tool (SWAT) and the Agricultural Policy Environmental EXtender (APEX) are widely used to assess the fate and transport of agricultural nutrient management practices on soluble and particulate phosphorus (P) loss in runoff. Soil P-cycling routines used in SWAT2012 revision 586, however, do not simulate the short-term effects of applying a concentrated source of soluble P, such as manure, to the soil surface where it is most vulnerable to runoff. We added a new set of soil P routines to SWAT2012 revision 586 to simulate surface-applied manure at field and subwatershed scales within Mahantango Creek watershed in south-central Pennsylvania. We corroborated the new P routines and standard P routines in two versions of SWAT (conventional SWAT, and a topographically driven variation called TopoSWAT) for a total of four modeling "treatments". All modeling treatments included 5 yr of measured data under field-specific, historical management information. Short-term "wash off" processes resulting from precipitation immediately following surface application of manures were captured with the new P routine whereas the standard routines resulted in losses regardless of manure application. The new routines improved sensitivity to key factors in nutrient management (i.e., timing, rate, method, and form of P application). Only the new P routines indicated decreases in soluble P losses for dairy manure applications at 1, 5, and 10 d before a storm event. The new P routines also resulted in more variable P losses when applying manure versus commercial fertilizer and represented increases in total P losses, as compared with standard P routines, with rate increases in dairy manure application (56,000 to 84,000 L ha). The new P routines exhibited greater than 50% variation among proportions of organic, particulate, and soluble P corresponding to spreading method. In contrast, proportions of P forms under the standard P routines varied less than 20%. Results suggest similar revisions to other agroecosystem watershed models would be appropriate. PMID- 27380070 TI - Validation of Sensor-Directed Spatial Simulated Annealing Soil Sampling Strategy. AB - Soil spatial variability has a profound influence on most agronomic and environmental processes at field and landscape scales, including site-specific management, vadose zone hydrology and transport, and soil quality. Mobile sensors are a practical means of mapping spatial variability because their measurements serve as a proxy for many soil properties, provided a sensor-soil calibration is conducted. A viable means of calibrating sensor measurements over soil properties is through linear regression modeling of sensor and target property data. In the present study, two sensor-directed, model-based, sampling scheme delineation methods were compared to validate recent applications of soil apparent electrical conductivity (EC)-directed spatial simulated annealing against the more established EC-directed response surface sampling design (RSSD) approach. A 6.8 ha study area near San Jacinto, CA, was surveyed for EC, and 30 soil sampling locations per sampling strategy were selected. Spatial simulated annealing and RSSD were compared for sensor calibration to a target soil property (i.e., salinity) and for evenness of spatial coverage of the study area, which is beneficial for mapping nontarget soil properties (i.e., those not correlated with EC). The results indicate that the linear modeling EC-salinity calibrations obtained from the two sampling schemes provided salinity maps characterized by similar errors. The maps of nontarget soil properties show similar errors across sampling strategies. The Spatial Simulated Annealing methodology is, therefore, validated, and its use in agronomic and environmental soil science applications is justified. PMID- 27380071 TI - Eco-Efficiency Model for Evaluating Feedlot Rations in the Great Plains, United States. AB - Environmental impacts attributable to beef feedlot production provide an opportunity for economically linked efficiency optimization. Eco-efficiency models are used to optimize production and processes by connecting and quantifying environmental and economic impacts. An adaptable, objective eco efficiency model was developed to assess the impacts of dietary rations on beef feedlot environmental and fiscal cost. The hybridized model used California Net Energy System modeling, life cycle assessment, principal component analyses (PCA), and economic analyses. The model approach was based on 38 potential feedlot rations and four transportation scenarios for the US Great Plains for each ration to determine the appropriate weight of each impact. All 152 scenarios were then assessed through a nested PCA to determine the relative contributing weight of each impact and environmental category to the overall system. The PCA output was evaluated using an eco-efficiency model. Results suggest that water, ecosystem, and human health emissions were the primary impact category drivers for feedlot eco-efficiency scoring. Enteric CH emissions were the greatest individual contributor to environmental performance (5.7% of the overall assessment), whereas terrestrial ecotoxicity had the lowest overall contribution (0.2% of the overall assessment). A well-balanced ration with mid-range dietary and processing energy requirements yielded the most eco- and environmentally efficient system. Using these results, it is possible to design a beef feed ration that is more economical and environmentally friendly. This methodology can be used to evaluate eco-efficiency and to reduce researcher bias of other complex systems. PMID- 27380072 TI - Effects of Riparian Buffer Vegetation and Width: A 12-Year Longitudinal Study. AB - Agricultural contributions of nitrogen are a serious concern for many water resources and have spurred the implementation of riparian buffer zones to reduce groundwater nitrate (NO). The optimum design for buffers is subject to debate, and there are few long-term studies. The objective of this project was to determine the effectiveness over time (12 yr) of buffer types (trees, switchgrass, fescue, native, and a control) and buffer widths (8 and 15 m) by measuring groundwater NO-N and dissolved organic carbon (DOC) trends. At the intermediate groundwater depth (1.5-2.1 m), NO-N reduction effectiveness was 2.5 times greater (46 vs. 16%) for the wider buffer, and, regardless of width, buffer effectiveness increased 0.62% yr. Buffer vegetative type was never statistically significant. In the deep-groundwater depth (2.1-3.5 m), there was no change in NO N removal over time, although the statistical interaction of width and vegetative type indicated a wide range of removal rates (19-82%). The DOC concentrations were analyzed at the field/buffer and buffer/stream sampling locations. Depending on location position and groundwater sampling depth, DOC concentrations ranged from 1.6 to 2.8 mg L at Year 0 and increased at a rate of 0.13 to 0.18 mg L yr but always remained low (<=5.0 mg L). Greater DOC concentrations in the intermediate-depth groundwater did not increase NO-N removal; redox measurements indicated intermittent reduced soil conditions may have been limiting. This study suggests that riparian buffer width, not vegetation, is more important for NO-N removal in the middle coastal plain of North Carolina for a newly established buffer. PMID- 27380073 TI - Trace Elements in Dominant Species of the Fenghe River, China: Their Relations to Environmental Factors. AB - The distribution of trace elements (TEs) in water, sediment, riparian soil and dominant plants was investigated in the Fenghe River, Northwestern China. The Fenghe River ecosystem was polluted with Cd, Cr, Hg and Pb. There was a high pollution risk in the midstream and downstream regions and the risk level for Cd was much higher than that of the other elements. The average values of bioconcentration coefficient for Cd and Zn were 2.21 and 1.75, respectively, indicating a large accumulation of Cd and Zn in the studied species. With broad ecological amplitudes, L. Levl. et Vant. Trin., and L. had the greatest TE concentrations in aboveground and belowground biomass of the studied species and were potential biomonitors or phytoremediators for the study area. Multivariate techniques including cluster analysis, correlation analysis, principal component analysis, and canonical correspondence analysis were used to analyze the relations between TE concentrations in plants and various environmental factors. The soil element concentration is the main factor determining the accumulation of TEs in plants. The co-release behavior of common pollutants and TEs drove the accumulation of Hg, Cd, and As in the studied plants. Significant enrichment of some elements in the Fenghe River has led to a decline in the biodiversity of plants. PMID- 27380074 TI - Chromium Release from a COPR-Contaminated Soil at Varying Water Content and Redox Conditions. AB - Many soils in the region of Kanpur, North India, are heavily affected by the leather industry and its upstream supplier sector, as indicated by elevated chromium (Cr) contents. Under reducing conditions-for instance, at water saturation after monsoon rain or flood irrigation-the dynamic and species distribution of Cr may be affected due to changes in redox potential (E). In this study, the influence of E on the speciation and release of Cr from a contaminated agricultural soil was investigated. A soil sample that was affected by hyperalkaline leachate from chromite ore processing residue, was taken and packed in soil columns, and subjected to a saturation-drainage-saturation cycle. After initial water saturation, the E dropped slowly to minimum values of around -100 mV (calculated to pH 7), while E was controlled by CrO/CrO(s), or CrO/(Fe,Cr)OOH redox couples. Soil drainage resulted in a quick return to oxidizing conditions; i.e., E > 300 mV. The Cr species distribution and release showed a clear trend with E. At the beginning of the experiment, under oxidizing and weakly reducing conditions (E range from >100 to 300 mV), Cr(VI) was released in particular. However, under moderately reducing conditions (E range from 100 to -100 mV), Cr was gradually immobilized and irreversible sequestered via reductive precipitation. The results presented in this study provide an improved understanding of the mobility of Cr(VI) in contaminated soils at varying water contents, which is essential for the evaluation of environmental risks in this region. PMID- 27380075 TI - Illinois River Nitrate-Nitrogen Concentrations and Loads: Long-term Variation and Association with Watershed Nitrogen Inputs. AB - The Illinois River is a major contributor of nitrate-N to the Mississippi River and the Gulf of Mexico, where nitrate is a leading cause of summertime benthic hypoxia. Corn-soybean production on tile-drained land is a leading source of nitrate-N in this river system, in addition to municipal wastewater discharge. We calculated annual nitrate-N loads in the Illinois River at Valley City from 1976 to 2014 by linear interpolation. Although there was not a significant trend in annual loads during the entire study period, there was a significant downward trend in flow-weighted nitrate-N concentration after 1990 despite high concentrations in 2013 after the 2012 drought. Multivariate regression analysis revealed a statistically significant association between annual flow-weighted nitrate-N concentration and cumulative residual agricultural N inputs to the watershed during a 6-yr window. This suggests that declines in flow-weighted nitrate-N concentration may reflect increasing N use efficiency in agriculture and a depletion of legacy N stored in the watershed. The watershed appears to have transitioned from a state of stationarity in nitrate concentration to nonstationarity. The average annual nitrate-N load at Valley City from 2010 to 2014 was 10% less than the 1980-1996 average load, indicating recent progress toward Illinois' nutrient loss reduction milestone of 15% reduction by 2025 and ultimate target of 45% reduction. PMID- 27380076 TI - Using the Provenance of Sediment and Bioavailable Phosphorus to Help Mitigate Water Quality Impact in an Agricultural Catchment. AB - The quality and health of surface waters can be impaired by sediment and sediment bound phosphorus (P). The Waituna Lagoon catchment in southern New Zealand has undergone agricultural intensification that has been linked to increases in sediment and sediment-bound bioavailable P (BAP) in the lagoon. Time-integrated samplers trapped suspended sediment from the water column, and their geochemical signature was compared with likely sources (stream banks, stream beds, topsoil, and subsoil) in each of the lagoon's contributing streams and rivers. The proportion of BAP, but not necessarily total P, within trapped sediment was much greater in samples from the Moffat and Carran Creeks than from the Waituna Creek, probably due to the erosion of organic-rich soils that had little capacity to retain P compared with the more mineral soils of the Waituna Creek. Annually, most BAP and sediment came from bank erosion, and strategies such as fencing out stock should focus on minimizing this throughout the catchment. However, when considering losses in space and time relative to the impact on the Waituna Lagoon, strategies the Waituna Creek catchment should also minimize contributions from topsoil in winter-spring, whereas in the Carran and Moffat Creek catchments strategies need to decrease P inputs (e.g., effluent) to Organic soils likely to lose much BAP in summer-autumn when the impact on the Lagoon is quickest. This study highlighted the need to identify sources and timings of BAP and sediment loss before recommending mitigation practices, which without this information may be slow or not succeed. PMID- 27380077 TI - Hydro-Climatological Influences on Long-Term Dissolved Organic Carbon in a Mountain Stream of the Southeastern United States. AB - In the past decade, significant increases in surface water dissolved organic carbon (DOC) have been reported for large aquatic ecosystems of the Northern Hemisphere and have been attributed variously to global warming, altered hydrologic conditions, and atmospheric deposition, among other factors. We analyzed a 25-yr DOC record (1988-2012) available for a forested headwater stream in the United States and documented two distinct regimes of stream DOC trends. From 1988 to 2001, annual mean volume-weighted DOC concentration (DOC, mg L) and annual DOC flux (kg ha yr) declined by 34 and 56%, respectively. During 1997 to 2012, the decline in DOC and DOC flux increased by 141 and 165%, respectively. Declining DOC from 1988 to 2001 corresponded to a decline in growing season runoff, which has the potential to influence mobilization of DOC from uplands to streams. Increasing DOC from 1997 to 2012 corresponded to increased precipitation early in the growing season and to an increase in the number and intensity of short-duration fall storms capable of mobilizing long-accrued DOC from forest litter and soils. In contrast, total annual runoff declined throughout the period. Rising air temperature, atmospheric acid deposition, and nitrogen depositions did not offer any plausible explanation for the observed bidirectional annual trends of stream DOC. Our study highlights the critical role of long-term datasets and analyses for understanding the impacts of climate change on carbon and water cycles and associated functions of aquatic and terrestrial ecosystems. PMID- 27380078 TI - Quantifying Sediment Provenance Using Multiple Composite Fingerprints in a Small Watershed in Oklahoma. AB - Quantitative information on sediment provenance is needed for improved calibration and validation of process-based soil erosion models. However, sediment source data are often limited due to difficulties in directly measuring source contributions at a watershed scale. Our objectives in this study were to estimate sediment source contributions in a 15-km watershed using analytical solutions to a three end-member mixing model using multiple composite fingerprints and to compare the results with those estimated with a single radionuclide, Cs. Surface soil samples were collected from 23 croplands, 19 rangelands, and 26 gully banks in the watershed, and 31 geochemical elements were analyzed for each sample. The elements served as tracers and were screened using statistical tests and range checks. The mean concentrations of all the nonconflict tracer pairs were used in the mixing model to calculate source contributions for the three sources. Results showed that although source contributions were strongly influenced by topography and land use, gully or subsoil erosion was found to be the main source of fine sediment in most subwatersheds. This study demonstrates that estimated source contributions may vary substantially among different composite fingerprints and that the use of multiple composite fingerprints greatly improves accuracy while reducing uncertainty. The source contributions estimated using multiple composite fingerprints agreed well with those estimated with Cs, with a correlation coefficient of 0.69 for gully contributions. This good agreement increases our confidence in using the multiple composite fingerprint method to identify sediment provenance in relatively small watersheds. PMID- 27380079 TI - Hydrologic Impacts of Municipal Wastewater Irrigation to a Temperate Forest Watershed. AB - Land application of municipal wastewater to managed forests is an important treatment and water reuse technology used globally, but the hydrological processes of these systems are not well characterized for temperate areas with annual rainfall of 1200 mm or greater. This study evaluated the impact of municipal wastewater irrigation to the local water balance at a 3000-ha land application facility where secondary-treated wastewater is land applied to a mixed hardwood-pine forest over 900 ha. Stable isotopes of hydrogen (H) and oxygen (O), chloride concentrations, and specific conductance were used in combination with hydrometric measurements to estimate the wastewater composition in groundwater, surface water, and at the watershed outlet during dry and wet seasonal periods and during one large rainfall event. Wastewater and water bodies receiving irrigation were found to have significantly higher deltaH, deltaO, specific conductance, and chloride concentrations. Using these tracers, a two component, three-end member geochemical mixing model estimated mean wastewater compositions in the surficial aquifer receiving irrigation from 47 to 73%. Surface water onsite was found to reflect the high wastewater composition in groundwater. Land-applied wastewater contributed an estimated 24% of total streamflow, with the highest wastewater compositions in surface water observed during major storm events and at low-flow conditions. Groundwater and surface water within the watershed were found to have proportionally higher wastewater compositions than expected based on the proportion of irrigation to rainfall received by these areas. PMID- 27380080 TI - Riverine Response of Sulfate to Declining Atmospheric Sulfur Deposition in Agricultural Watersheds. AB - Sulfur received extensive study as an input to terrestrial ecosystems from acidic deposition during the 1980s. With declining S deposition inputs across the eastern United States, there have been many studies evaluating ecosystem response, with the exception of agricultural watersheds. We used long-term (22 and 18 yr) sulfate concentration data from two rivers and recent (6 yr) data from a third river to better understand cycling and transport of S in agricultural, tile-drained watersheds. Sulfate concentrations and yields steadily declined in the Embarras (from ~10 to 6 mg S L) and Kaskaskia rivers (from 7 to 3.5 mg S L) during the sampling period, with an overall -23.1 and -12.8 kg S ha yr balance for the two watersheds. There was evidence of deep groundwater inputs of sulfate in the Salt Fork watershed, with a much smaller input to the Embarras and none to the Kaskaskia. Tiles in the watersheds had low sulfate concentrations (<10 mg S L), similar to the Kaskaskia River, unless the field had received some form of S fertilizer. A multiple regression model of runoff (cm) and S deposition explained much of the variation in Embarras River sulfate ( = 0.86 and 0.80 for concentrations and yields; = 46). Although atmospheric deposition was much less than outputs (grain harvest + stream export of sulfate), riverine transport of sulfate reflected the decline in inputs. Watershed S balances suggest a small annual depletion of soil organic S pools, and S fertilization will likely be needed at some future date to maintain crop yields. PMID- 27380081 TI - Effect of Harsh or Mild Extraction of Soil on Pesticide Leaching to Groundwater. AB - Assessment of leaching to groundwater is an important aspect of pesticide risk assessment. The first leaching tier usually consists of simulations with leaching scenarios based on pesticide-soil properties derived from laboratory studies. Because the extractability of pesticide residues in such studies decreases with time, the harshness of the extraction method influences these pesticide-soil properties. This study investigates the effect of using a mild or harsh extraction method on simulated leaching to groundwater with consideration of substances with a range of half-lives and organic matter sorption coefficient values for selected leaching scenarios. The model for linking the concentrations of the mild and the harsh systems was based on laboratory studies with two pesticides and a Dutch sandy soil and was tested against Canadian field studies with atrazine (6-chloro-2-ethyl-4-isopropyl-1,3,5-triazine-2,4-diamine). The degradation rate and the aged-sorption parameters of each "mild" soil-substance system were derived from a hypothetical laboratory incubation study using prescribed parameter values for the corresponding "harsh" soil-substance system. Simulations were performed for three European leaching scenarios (United Kingdom, France, Portugal). For the best-guess parameter set, the leaching concentrations of the harsh system were approximately equal to those of the mild system at leaching concentrations greater than 1 MUg L and were at most approximately a factor of two higher than those of the mild systems at mild leaching concentrations between 0.01 and 0.1 MUg L. However, an extreme parameter set led to harsh leaching concentrations that were at most approximately 10 times higher than the mild leaching concentrations at levels between 0.01 and 0.1 MUg L. PMID- 27380082 TI - Assessing the Success of Regional Measures for Lowering Agricultural Nutrient Pollution in Headwater Streams. AB - Lowland waters in Northern Ireland experience elevated agricultural phosphorus (P) inputs, and in response a variety of control measures targeting farm nutrient management have been implemented. Their efficacy in lowering nitrogen (N) and P exports and improving water quality is examined in 40 headwater streams from 1990 to 2009, and to 2014 for 24 of these. Over this period manure production in the study catchments declined by 7%, but regional chemical fertilizer inputs declined by 37% for N and 79% for P, and the regional nutrient surplus was lowered by 18% for N and 49% for P. Diminished pollution by organic wastes meant that 85% of streams exhibited chemistry suitable for salmonids in 2009 compared to 40% in 1990. Flow-weighted mean concentrations (FWMCs) of nutrients declined between 1990 and 2009, and their correlations with catchment stocking rates became stronger over time. For catchments with manure inputs <16.6 kg P ha, total P and nitrate FWMCs declined from 123 +/- 19 MUg P L and 1.92 +/- 0.5 mg N L in 1990 at rates of 2.2 +/- 0.5 and 30 +/- 10 MUg L yr, respectively. For catchments with higher manure inputs the respective rates of decline were greater at 5.8 +/- 1.0 MUg P L yr and 160 +/- 20 MUg N L yr from 1990 concentrations of 270 +/- 25 MUg P L and 5.99 +/- 0.4 mg N L. Although now lower, P concentrations in the more highly stocked catchments still exceed regional nutrient standards so that the identification of further factors impinging on nutrient losses is critical if such standards are to be achieved. PMID- 27380083 TI - Assessing the Influence of Calcium Fluoride on Pyrite Electrochemical Dissolution and Mine Drainage pH. AB - We investigated the influence of dissolved calcium fluoride, CaF(aq), on the electrochemical dissolution of pyrite and the corresponding environmental effects on acid mine drainage (AMD). The experimental results showed that CaF(aq) promotes pyrite electrochemical dissolution. When the CaF(aq) concentration increased from 0 to 10 mg L up to saturation, the promoting efficiency was 15.80 and 57.25%, respectively. The reason for this phenomenon is that F and Fe form FeF, and at a higher scan potential, F and Fe form the ion complex FeF. The mechanisms include: (i) the decreasing charge transfer resistance at the double layer due to the iron fluorine complex formation; and (ii) the decreasing passivation resistance at the cover layer due to the strong penetration of F ions through it into the double layer. Although the hydrolysis reaction of F in solution could increase the pH value of mine drainage, the AMD was significantly aggravated because CaF(aq) promoted the pyrite electrochemical dissolution. PMID- 27380084 TI - Total Phosphorus Concentration Trends in 40 Iowa Rivers, 1999 to 2013. AB - Excessive phosphorus (P) in rivers is prompting states to develop strategies to reduce P concentrations and export. The goal of this study was to assess the current condition by analyzing trends in total P (TP) concentrations at 40 river monitoring sites in Iowa for the period 1998 to 2013. We used monthly river monitoring data collected by the State of Iowa at ambient sites located beyond the influence of point sources or cities. Study objectives were to assess the presence of any linear trends in the TP concentration data using a time-series method that accounted for temporal correlation in the data and discharge and to combine the trend information from individual sites into an assessment of the statewide rate of change in river TP concentrations. Results indicated that annual TP concentrations were significantly decreasing at 12 sites ( < 0.05), with concentrations ranging from 7.5% (Maple River) to 2.6% (Boyer River) and averaging 4.1% for the 12 sites. No statistically significant change was measured at 28 sites ( > 0.05), although all but four of these sites had decreasing concentrations. As a population of sampled rivers across Iowa, TP concentrations were declining at an annual rate of approximately 2.6%. The decreasing trends are consistent with reported reductions in sediment concentrations measured in the Raccoon River and with decreasing trends detected in other midwestern rivers. We attribute the decreasing TP trends primarily to improvements in conservation and land management. Although reducing nonpoint source TP concentrations in Iowa rivers will be a tremendous challenge for the agricultural community, progress is being made toward meeting this goal with existing programs. PMID- 27380085 TI - Aeration-Induced Changes in Temperature and Nitrogen Dynamics in a Dimictic Lake. AB - Low levels of oxygen (O) in the hypolimnion layer of lakes are harmful to benthic animals and fish; they may also adversely affect nutrient cycles. Artificial aeration is often used in lake management to counteract these problems, but the effects of aeration on nitrogen (N) cycling are not known. We studied the effects of hypolimnetic aeration on N dynamics and temperature in a eutrophic lake by comparing continuous and pulsed aeration with a nonaerated station. Aeration decreased the accumulation of NH-N deep in the lake (20-33 m) by supplying O for nitrification, which in turn provided substrate for denitrification and promoted N removal. Aeration also increased the temperature in the hypolimnion. Denitrification rate was highest in the nonaerated deep areas (average, 7.62 mg N m d) due to very high rates during spring turnover of the water column, demonstrating that natural turnover provides O for nitrification. During stratification, denitrification was highest at the continuously aerated station (4.06 mg N m d) and lowest at the nonaerated station (3.02 mg N m d). At the periodically aerated station, aeration pauses did not restrict the increase in temperature but resulted in accumulation of NH-N and decreased the contribution of denitrification as a nitrate reduction process. Our findings demonstrate that hypolimnetic aeration can substantially affect N cycling in lakes and that the effect depends on the aeration strategy. Because N is one of the main nutrients controlling eutrophication, the effects of aeration methods on N removal should be considered as part of strategies to manage water quality in lakes. PMID- 27380087 TI - Phosphorus Release to Floodwater from Calcareous Surface Soils and Their Corresponding Subsurface Soils under Anaerobic Conditions. AB - Enhanced phosphorus (P) release from soils to overlying water under flooded, anaerobic conditions has been well documented for noncalcareous and surface soils, but little information is available for calcareous and subsurface soils. We compared the magnitude of P released from 12 calcareous surface soils and corresponding subsurface soils to overlying water under flooded, anaerobic conditions and examined the reasons for the differences. Surface (0-15 cm) and subsurface (15-30 cm) soils were packed into vessels and flooded for 8 wk. Soil redox potential and concentrations of dissolved reactive phosphorus (DRP) and total dissolved Ca, Mg, Fe, and Mn in floodwater and pore water were measured weekly. Soil test P was significantly smaller in subsurface soils than in corresponding surface soils; thus, the P release to floodwater from subsurface soils was significantly less than from corresponding surface soils. Under anaerobic conditions, floodwater DRP concentration significantly increased in >80% of calcareous surface soils and in about 40% of subsurface soils. The increase in floodwater DRP concentration was 2- to 17-fold in surface soils but only 4- to 7-fold in subsurface soils. With time of flooding, molar ratios of Ca/P and Mg/P in floodwater increased, whereas Fe/P and Mn/P decreased, suggesting that resorption and/or reprecipitation of P took place involving Fe and Mn. Results indicate that P release to floodwater under anaerobic conditions was enhanced in most calcareous soils. Surface and subsurface calcareous soils in general behaved similarly in releasing P under flooded, anaerobic conditions, with concentrations released mainly governed by initial soil P concentrations. PMID- 27380086 TI - Surface Runoff of Pesticides from a Clay Loam Field in Sweden. AB - Pesticides stored at or close to the soil surface after field application can be mobilized and transported off the field when surface runoff occurs. The objective of our study was to quantify the potential pesticide losses in surface runoff from a conventionally managed agricultural field in a Swedish climate. This was achieved by measuring surface runoff volumes and concentrations in runoff of six spring-applied pesticides and autumn-applied glyphosate and its metabolite aminomethylphosphonic acid (AMPA). Measurements were performed for 3 yr both during the growing seasons and during intervening winter snowmelt periods on a clay loam field close to Uppsala. During growing seasons, surface runoff was generated on only five occasions during one 25-d period in 2012 when the infiltration capacity of the soil may have been reduced by structural degradation due to large cumulative rainfall amounts after harrowing. Concentrations in surface runoff exceeded Swedish water quality standards in all samples during this growing season for diflufenican and pirimicarb. Surface runoff was generated during three snowmelt periods during the winter of 2012-2013. All of the applied pesticides were found in snowmelt samples despite incorporation of residues by autumn plowing, degradation, and leaching into the soil profile during the period between spraying and sampling. Concentrations of glyphosate ranged from 0.12 to 7.4 MUg L, and concentrations of AMPA ranged from 0 to 2.7 MUg L. Our results indicate that temporal changes in hydraulic properties during the growing season and when the soil freezes during winter affect pesticide losses through surface runoff. PMID- 27380088 TI - Phosphorus Leaching in Soils Amended with Animal Manures Generated from Modified Diets. AB - New dietary modifications for dairy (reducing P content in feed) and poultry (addition of feed additives such as phytase) aim to reduce P excretion in manures. Our objective was to investigate if dietary changes were effective at reducing P leaching loss on land application of manures. We used 54 undisturbed lysimeters (30 cm diameter, 50 cm deep) collected from three typical mid-Atlantic soils. Lysimeters received 85 kg total P ha from fertilizer (superphosphate), dairy manures generated from low- or high-P diets, or broiler litters generated from normal diet or reduced P- and phytase-amended diets. Lysimeters were irrigated with 50 mm of water each week for 9 wk. The major forms of P in the leachate were dissolved (dissolved unreactive > dissolved reactive P [DRP]) rather than particulate (total particulate P). The higher P solubility (100%) in superphosphate resulted in greater leaching of DRP, whereas the lower P solubility (<30%) in dairy manures or broiler litters resulted in lower DRP leaching from soils. Preferential flow in two soils caused greater DRP leaching; this effect was more pronounced in the superphosphate-amended than in the manure/litter-amended lysimeters. The dairy and poultry dietary modification was effective at reducing the amount of P in manures and litters. However, the application of treatments at similar P rate (85 kg ha) resulted in the addition of a higher amount of manure (54-66%) in lysimeters that received low-P dairy manure-amended and phytase-amended broiler litter, which then controlled P leaching from soils. PMID- 27380089 TI - Mass Balance of Water and Nitrogen in the Mounded Drainfield of a Drip-Dispersal Septic System. AB - Quantitative assessment of nitrogen (N) loading from septic systems is needed to protect groundwater contamination. We determined the mass balance of water and N in the mounded drainfield of a drip-dispersal septic system. Three lysimeters (152.4 cm long, 91.4 cm wide, 91.4 cm high, with 1:1 side slope) were constructed using pressure-treated wood to mimic mounded drainfields. Of total water inputs, septic tank effluent (STE) added 57% water and natural rainfall added 43% water from January 2013 to January 2014. Outputs included leached water (46%) from the lysimeters over 67 sampling events ( = 15 daily and = 52 weekly flow-weighted), potential evapotranspiration (28%), and water stored in the drainfields (26%). Over 13 mo, each drainfield received 227 g of total N (STE, 99%; rainfall, 1%), of which 33% leached, 23% accumulated in the drainfield, and 6% was taken up by grass, with the remainder (38%) estimated to be gaseous N loss. Using these data, the leaching of water from 2.5 million drip-dispersal drainfields in the state of Florida was estimated to be 2.29 * 10 L yr, which would transport 2.4 * 10 kg of total N yr from the drainfields to shallow groundwater. Further reduction of N below drainfields in the soil profile could be expected before STE reaches groundwater. Our results provide quantitative information on the water and N loading and can be used to optimize drainfield conditions to attenuate N and protect groundwater quality. PMID- 27380090 TI - Path Analyses of Grain P, Zn, Cu, Fe, and Ni in a Biosolids-Amended Dryland Wheat Agroecosystem. AB - Land application of biosolids is an effective means of recycling plant nutrients and is the primary method of biosolids reuse endorsed by the USEPA. One issue concerning biosolids application is the extent of the contribution of biosolids borne plant nutrients to the overall crop concentration and uptake or removal of these nutrients. We studied the effects of biosolids application on wheat ( L.) grain P, Zn, Cu, Fe, and Ni concentrations and uptake (removal) at two dryland agroecosystem sites from 1993 to 2014. We hypothesized that biosolids would have the greatest impact on wheat grain and uptake compared with ammonium bicarbonate diethylenetriaminepentaacetic acid (AB-DTPA)-extractable nutrient levels, soil pH, or soil organic C concentrations. We used path analyses in combination with multiple linear regression to differentiate the direct, indirect, and total effects of cumulative biosolids applications, soil AB-DTPA, soil pH, and organic C. Biosolids rates, applied biennially from 1993 to 2014 at the beginning of a wheat-fallow rotation, were 0, 2.24, 4.48, 6.72, 8.96, and 11.2 Mg ha. None of the parameters had significant direct, indirect, or total effects on grain concentrations. Biosolids applications had the greatest positive direct impact compared with AB-DTPA levels, soil pH, or soil organic C on P, Zn, Fe, and Ni uptake (removal), whereas AB-DTPA had the greatest positive direct impact on Cu uptake. Soil AB-DTPA, pH, and organic C directly affected some grain concentrations and cumulative uptake, but no consistent trends were noted. This pathway approach allowed differentiation between causation and simple correlation for the effects of cumulative biosolids applications on wheat P, Zn, Cu, Fe, and Ni cumulative uptake but did not provide these same results for grain concentrations. PMID- 27380091 TI - Solubilization of Polycyclic Aromatic Hydrocarbons by Single and Binary Mixed Rhamnolipid-Sophorolipid Biosurfactants. AB - Biosurfactants are promising additives for surfactant enhanced remediation (SER) technologies due to their low toxicity and high biodegradability. To develop green and efficient additives for SER, the aqueous solubility enhancements of polycyclic aromatic hydrocarbons (PAHs; naphthalene, phenanthrene, and pyrene) by rhamnolipid (RL) and sophorolipid (SL) biosurfactants were investigated in single and binary mixed systems. The solubilization capacities were quantified in terms of the solubility enhancement factor, molar solubilization ratio (MSR), and micelle-water partition coefficient (). Rughbin's model was applied to evaluate the interaction parameters (beta) in the mixed RL-SL micelles. The solubility of the PAHs increased linearly with the glycolipid concentration above the critical micelle concentration (CMC) in both single and mixed systems. Binary RL-SL mixtures exhibited greater solubilization than individual glycolipids. At a SL molar fraction of 0.7 to 0.8, the solubilization capacity was the greatest, and the MSR and reached their maximum values, and beta values became positive. These results suggest that the two biosurfactants act synergistically to increase the solubility of the PAHs. The solubilization capacity of the RL-SL mixtures increased with increasing temperature and decreased with increasing salinity. The aqueous solubility of phenanthrene reached a maximum value at pH of 5.5. Moreover, the mixed RL-SL systems exhibited a strong ability to solubilize PAHs, even in the presence of heavy metal ions. These mixed biosurfactant systems have the potential to improve the performance of SER technologies using biosurfactants to solubilize hydrophobic organic contaminants by decreasing the applied biosurfactant concentration, which reduces the costs of remediation. PMID- 27380092 TI - Reducing Phosphorus Runoff and Leaching from Poultry Litter with Alum: Twenty Year Small Plot and Paired-Watershed Studies. AB - Treating poultry litter with alum has been shown to lower ammonia (NH) emissions and phosphorus (P) runoff losses. Two long-term studies were conducted to assess the effects of alum-treated poultry litter on P availability, leaching, and runoff under pasture conditions. From 1995 to 2015, litter was applied annually in a paired watershed study comparing alum-treated and untreated litter and in a small plot study comparing 13 treatments (an unfertilized control, four rates of alum-treated litter, four rates of untreated litter, and four rates of NHNO). In the paired watershed study, total P loads in runoff were 231% higher from pasture receiving untreated litter (1.96 kg P ha) than from that receiving alum-treated litter (0.85 kg P ha). In both studies, alum-treated litter resulted in significantly higher Mehlich III P (M3-P) and lower water-extractable P at the soil surface, reflecting greater retention of applied P and lesser availability of that P to runoff or leaching. In soils fertilized with alum-treated litter, M3 P was much higher when analyzed by inductively coupled argon plasma emission spectrometry than by colorimetry, possibly due to the formation of aluminum phytate. Indeed, alum-treated poultry litter leached less P over the 20-yr study: M3-P at 10 to 50 cm was 266% greater in plots fertilized with untreated litter (331 kg M3-P ha) than with alum-treated litter (124 kg M3-P ha). This research provides compelling evidence that treating poultry litter with alum provides short-term and long-term benefits to P conservation and water quality. PMID- 27380093 TI - Development of a New Manure Amendment for Reducing Ammonia Volatilization and Phosphorus Runoff from Poultry Litter. AB - Treating poultry litter with alum is a best management practice that reduces phosphorus (P) runoff and ammonia (NH) emissions. However, alum prices have increased substantially during the past decade. The goal of this research was to develop inexpensive manure amendments that are as effective as alum in reducing NH volatilization and P runoff. Sixteen amendments were developed using mixtures of alum mud, bauxite ore, sulfuric acid, liquid alum, and water. Alum mud is the residual left over from alum manufacture when produced by reacting bauxite with sulfuric acid. A laboratory NH volatilization study was conducted using 11 treatments: untreated poultry litter, poultry litter treated with liquid or dry alum, or eight new mixtures. All of the litter amendments tested resulted in significantly lower NH volatilization than untreated litter. Dry and liquid alum reduced NH losses by 86 and 75%, respectively. The eight new litter amendments reduced NH losses from 62 to 73% compared with untreated litter, which was not significantly different from liquid alum; the three most effective mixtures were not significantly different from dry alum. Water-extractable P (WEP) was significantly reduced by all of the amendments, three of which resulted in significantly lower WEP than dry alum. The most promising new amendments were mixtures of alum mud, bauxite, and sulfuric acid. The potential impact of these amendments could be enormous because they could be produced for less than half the price of alum while being as effective in reducing NH emissions and P runoff. PMID- 27380094 TI - Implications of Using Thermal Desorption to Remediate Contaminated Agricultural Soil: Physical Characteristics and Hydraulic Processes. AB - Given the recent increase in crude oil production in regions with predominantly agricultural economies, the determination of methods that remediate oil contamination and allow for the land to return to crop production is increasingly relevant. Ex situ thermal desorption (TD) is a technique used to remediate crude oil pollution that allows for reuse of treated soil, but the properties of that treated soil are unknown. The objectives of this research were to characterize TD treated soil and to describe implications in using TD to remediate agricultural soil. Native, noncontaminated topsoil and subsoil adjacent to an active remediation site were separately subjected to TD treatment at 350 degrees C. Soil physical characteristics and hydraulic processes associated with agricultural productivity were assessed in the TD-treated samples and compared with untreated samples. Soil organic carbon decreased more than 25% in both the TD-treated topsoil and the subsoil, and total aggregation decreased by 20% in the topsoil but was unaffected in the subsoil. The alteration in these physical characteristics explains a 400% increase in saturated hydraulic conductivity in treated samples as well as a decrease in water retention at both field capacity and permanent wilting point. The changes in soil properties identified in this study suggest that TD-treated soils may still be suitable for sustaining vegetation, although likely at a slightly diminished capacity when directly compared with untreated soils. PMID- 27380095 TI - Influence of Organic Amendment and Compaction on Nutrient Dynamics in a Saturated Saline-Sodic Soil from the Riparian Zone. AB - Cattle grazing in wet riparian pastures may influence nutrient dynamics due to nutrient deposition in feces and urine, soil compaction, and vegetation loss. We conducted a lab incubation study with a saline-sodic riparian soil to study nutrient (N, P, S, Fe, Mn, Cu, and Zn) dynamics in soil pore water using Plant Root Simulator (PRS) probes and release of nutrients into the overlying ponded water during flooding. The treatment factors were organic amendment (manure, roots, and unamended control), compaction (compacted, uncompacted), and burial time (3, 7, and 14 d). Amendment treatment had the greatest impact on nutrient dynamics, followed by burial time, whereas compaction had little impact. The findings generally supported our hypothesis that organic amendments should first increase nitrate loss, then increase Mn mobility, then Fe mobility and associated release of P, and finally increase sulfate loss. Declines in nitrate due to amendment addition were small because nitrate was at low levels in all treatments due to high denitrification potential instead of being released to soil pore water or overlying water. Addition of organic amendment strongly increased Mn and Fe concentrations in overlying water and of adsorbed Fe on PRS probes but only increased Mn on PRS probes on Day 3 due to subsequent displacement from ion exchange membranes. Transport of P to overlying water was increased by organic amendment addition but less so for manure than roots despite higher P on PRS probes. The findings showed that saline-sodic soils in riparian zones are generally a nutrient source for P and are a nutrient sink for N as measured using PRS probes after 3 to 7 d of flooding. PMID- 27380096 TI - Use of Dehydrated Agar to Estimate Microbial Water Quality for Horticulture Irrigation. AB - Petrifilms are dehydrated agar culture plates that have been used to quantify colony forming units (CFU) mL of either aerobic bacteria (Petrifilm-AC) or fungus (Petrifilm-YM), depending on substrate composition. Microbes in irrigation systems can indicate biofilm risk and potential clogging of irrigation emitters. The research objective was to compare counts on Petrifilms versus traditional, hydrated-agar plates using samples collected from recirculated irrigation waters and cultures of isolated known species. The estimated count (in CFU mL) from a recirculated irrigation sample after 7 d of incubation on Petrifilm-YM was only 5.5% of the count quantified using sabouraud dextrose agar (SDA) with chloramphenicol after 14 d. In a separate experiment with a known species, Petrifilm-YM did not successfully culture zoospores of . Isolates of viable zoospores were cultured successfully on potato-dextrose agar (PDA), with comparable counts with a vegetable juice medium supplemented with the antibiotics pimaricin, ampicillin, rifamycin, pentochloronitrobenzene and hymexazol (PARP-H). The quantification of pv. Begoniaceae on Petrifilm-AC was not significantly different ( < 0.05) than on PDA, but was lower than on Reasoner and Goldrich agar (R2A) or with a hemocytometer. The current formulation of Petrifilm-YM is unlikely to be a useful monitoring method for plant pathogens in irrigation water because of the inability to successfully culture oomycetes. However, Petrifilm-AC was an effective method to quantify bacteria and can provide an easy-to-use on farm tool to monitor biofilm risk and microbial density. PMID- 27380097 TI - Predicting Phosphorus Release from Anaerobic, Alkaline, Flooded Soils. AB - Anaerobic conditions induced by prolonged flooding often lead to an enhanced release of phosphorus (P) to floodwater; however, this effect is not consistent across soils. This study aimed to develop an index to predict P release potential from alkaline soils under simulated flooded conditions. Twelve unamended or manure-amended surface soils from Manitoba were analyzed for basic soil properties, Olsen P (Ols-P), Mehlich-3 extractable total P (M3P), Mehlich-3 extractable molybdate-reactive P (M3P), water extractable P (WEP), soil P fractions, single-point P sorption capacity (P), and Mehlich-3 extractable Ca (M3Ca), and Mg (M3Mg). Degree of P saturation (DPS) was calculated using Ols-P, M3P or M3P as the intensity factor, and an estimated adsorption maximum based on either P or M3Ca + M3Mg as the capacity factor. To develop the model, we used the previously reported floodwater dissolved reactive P (DRP) concentration changes during 8 wk of flooding for the same unamended and manured soils. Relative changes in floodwater DRP concentration (DRP), calculated as the ratio of maximum to initial DRP concentration, ranged from 2 to 15 across ten of the soils, but were <=1.5 in the two soils with the greatest clay content. Partial least squares analysis indicated that DPS3 calculated using M3P as the intensity factor and (2 * P) + M3P as the capacity factor with clay percentage can effectively predict DRP ( = 0.74). Results suggest that P release from a soil to floodwater may be predicted using simple and easily measurable soil properties measured before flooding, but validation with more soils is needed. PMID- 27380098 TI - Effect of a Biological Additive on Nitrogen Losses from Pig Slurry during Storage. AB - Additives applied to animal manure slurries can affect the chemical composition and the biological processes of slurries during storage, with possible improvement of their management and reduction of environmental problems. Some new formulations are marketed claiming a nitrogen (N) removal effect due to denitrification, with the consequence of a reduced N content in the manure after storage. This study evaluated the effects of one of these commercial additives (BACTYcomplex) on slurry characteristics and N losses at a commercial piggery. The additive was applied to four different sectors of the piggery, each with an independent under-floor slurry pit; four other sectors served as controls without treatment. Pits were emptied every 4 wk, and the manure was analyzed for total and ammonia-N and total and volatile solids. Slurry samples from the last month of the on-farm assessment were removed and stored thermostatically in vessels external to the piggery. A subsample of slurry that was treated with the additive at the piggery was treated with an additional dose of additive at the beginning of long-term storage. The additive did not change the composition of the slurry during in-house storage (4 wk duration). During the 155 d of external thermostatic storage, the total solids content of treated slurry was reduced by 18% compared with control slurry, but the N content and composition of treated slurry was unaffected. The additive had a positive effect in accelerating the stabilization of the slurry but did not modify N losses. PMID- 27380099 TI - Manure Injection Affects the Fate of Pirlimycin in Surface Runoff and Soil. PMID- 27380100 TI - Determining Strength: A Case for Multiple Methods of Measurement. AB - Muscle strength is often measured through the performance of a one-repetition maximum (1RM). However, we that feel a true measurement of 'strength' remains elusive. For example, low-load alternatives to traditional resistance training result in muscle hypertrophic changes similar to those resulting from traditional high-load resistance training, with less robust changes observed with maximal strength measured by the 1RM. However, when strength is measured using a test to which both groups are 'naive', differences in strength become less apparent. We suggest that the 1RM is a specific skill, which will improve most when training incorporates its practice or when a lift is completed at a near-maximal load. Thus, if we only recognize increases in the 1RM as indicative of strength, we will overlook many effective and diverse alternatives to traditional high-load resistance training. We wish to suggest that multiple measurements of strength assessment be utilized in order to capture a more complete picture of the adaptation to resistance training. PMID- 27380102 TI - Decreasing Falls With Injury Rates: Development of a Support Staff Falls Advocate Program. AB - Falls with injury are a persistent patient safety challenge in the acute care setting. This article describes the creation and implementation of a Certified Falls Prevention Advocate (CFPA) program on a medical-surgical unit. The program created standardization of nursing support staff involvement in falls prevention and engaged them as members of the interdisciplinary team. The CFPA program was an important element in the unit's improvement in falls with injury rates. The mean falls with injury rate decreased from 1.115 to 0.178 per 1000 patient-days over a 1-year period. PMID- 27380101 TI - Physiological and Biomechanical Responses to Running on Lower Body Positive Pressure Treadmills in Healthy Populations. AB - BACKGROUND: Lower body positive pressure treadmills (LBPPTs) aim to reduce musculoskeletal loading during running. As LBPPTs have become more commercially available, they have become integrated into athletic performance and clinical rehabilitation settings. Consequentially, published research examining the biomechanical and physiological responses to unweighted running has increased. OBJECTIVE: The purpose of this systematic review was to synthesize the literature in an attempt to provide researchers and clinicians with a comprehensive review of physiologic and biomechanical responses to LBPPT running. METHODS: Through a generic search of PubMed, CINAHL, MEDLINE, and SPORTDiscus using a comprehensive list of search terms related to LBPPT, unweighting, and body weight support during running, we identified all peer-reviewed publications that included LBPPT running. Two reviewers independently evaluated the quality of studies using a modified Downs and Black checklist for non-randomized studies. RESULTS: A total of 15 articles met the inclusion criteria for this review. Peak and active vertical ground-reaction forces were consistently reduced with unweighting, but regional loading within the foot was also altered towards a forefoot strike. LBPPTs also provide some horizontal assistance. Neuromuscular activation is generally reduced with LBPPTs, but the stabilizer muscle groups may respond differently than the propulsive muscle groups. Submaximal heart rate and volume oxygen consumption are reduced with unweighting, but physiologic response remains generally unchanged at maximal intensities. CONCLUSIONS: The current literature suggests that LBPPTs are effective in allowing individuals to achieve a given metabolic stimulus with reduced musculoskeletal loading. However, LBPPTs not only reduce impact but also change neuromuscular activation and biomechanics in a complex manner. Thus, clinicians must account for the specific biomechanical and physiological alterations induced by LBPPTs when designing training programs and rehabilitation protocols. PMID- 27380103 TI - Neutrophil gelatinase-associated lipocalin worsens ischemia/reperfusion damage of kidney cells by autophagy. AB - This study aimed to explore the influence of neutrophil gelatinase-associated lipocalin on autophagy and its role in ischemia/reperfusion injury in human kidney-2 (HK-2) cells during acute kidney injury (AKI). HK-2 cells were given hypoxia/reoxygenation treatment for different times to simulate ischemia/reperfusion injury. Autophagy was evaluated by western blot and immunofluorescence of GFP-LC3. Cell viability was tested to reflect the degree of cell damage. The autophagy inhibitor 3-MA was used to inhibit autophagy and determine the role of autophagy in ischemia/reperfusion injury. HK-2 cells were hypoxia for 1 h, followed by reoxygenation treatment for 24 h. These cells were then exposed to human recombinant protein neutrophil gelatinase-associated lipocalin (NGAL) (50, 100, 200, 400, or 1000 ng/mL) with or without 3-MA. Our results showed that autophagy was induced by hypoxia treatment and was further enhanced by reoxygenation after hypoxia treatment. Cell viability was decreased with the inhibition of autophagy in the process. Autophagic flux was further induced with NGAL (>200 ng/mL), while cell viability declined in this condition. Cell viability was recovered when autophagy was inhibited. These results indicate that autophagy plays, in part, a protective role in renal ischemia/reperfusion injury. Furthermore, the data suggest that NGAL strengthens the level of autophagy in this process. Overall, a large quantity of NGAL produced by renal proximal tubular epithelial cells may induce excessive autophagy and increase renal ischemia/reperfusion injury in acute kidney injury. PMID- 27380104 TI - Analgesic Effects of Ultrasound-Guided Serratus-Intercostal Plane Block and Ultrasound-Guided Intermediate Cervical Plexus Block After Single-Incision Transaxillary Robotic Thyroidectomy: A Prospective, Randomized, Controlled Trial. AB - BACKGROUND AND OBJECTIVES: Single-incision transaxillary robotic thyroidectomy (START) requires substantial tissue disruption, which produces moderate-to-severe pain in the axilla and neck areas during the early postoperative period. This study aimed to investigate the analgesic effects of ultrasound-guided serratus intercostal plane blocks and intermediate cervical plexus blocks (CPBs) on the early postoperative pain after START. METHODS: We randomized 22 patients to undergo either ultrasound-guided serratus-intercostal plane and intermediate CPBs (the block group, n = 11) or to not undergo any block (the control group, n = 11). We compared postoperative axillary pain, postoperative neck pain, and analgesic use between the groups during the first 24 hours. The rescue analgesics were intravenous fentanyl (0.5 MUg/kg) in the postanesthesia care unit, and intravenous ketorolac tromethamine (30 mg) in the general ward. RESULTS: The block group showed consistently lower pain scores than the control group in the axillary area in the first 24 hours and in the neck area only in the first 3 hours after surgery. The numbers (proportions) of patients who required analgesics were 11 (100%) in the control group and 6 (54.5%) in the block group during the first 24 hours (P = 0.035). No adverse effect was observed related to the peripheral nerve blocks. CONCLUSIONS: After START, a serratus-intercostal plane block performed at the level of the third rib was an effective analgesic technique for axillary pain; however, the clinical effectiveness of intermediate CPB for neck pain may be limited. PMID- 27380105 TI - A Comparison of Combined Suprascapular and Axillary Nerve Blocks to Interscalene Nerve Block for Analgesia in Arthroscopic Shoulder Surgery: An Equivalence Study. AB - BACKGROUND AND OBJECTIVES: The primary objective of this study was to compare the analgesic efficacy of combined suprascapular and axillary nerve block (SSAX) with interscalene block (ISB) after arthroscopic shoulder surgery. Our hypothesis was that ultrasound-guided SSAX would provide postoperative analgesia equivalent to ISB. METHODS: Sixty adult patients undergoing arthroscopic shoulder surgery received either SSAX or ISB prior to general anesthesia, in a randomized fashion. Pain scores, satisfaction, and adverse effects were recorded in the recovery room, 6 hours, 24 hours, and 7 days after surgery. RESULTS: Combined suprascapular and axillary nerve block provided nonequivalent analgesia when compared with ISB at different time points postoperatively, except on postoperative day 7. Interscalene block had better mean static pain score in the recovery room (ISB 1.80 [95% confidence interval [CI], 1.10-2.50] vs SSAX 5.45 [95% CI, 4.40-6.49; P < 0.001]). At 24 hours, SSAX had better mean static pain score (ISB 6.35 [95% CI, 5.16-7.54] vs SSAX 3.92 [95% CI, 2.52-5.31]; P = 0.01) with similar satisfaction between the groups. CONCLUSIONS: Combined suprascapular and axillary nerve block provides nonequivalent analgesia compared with ISB after arthroscopic shoulder surgery. While SSAX provides better quality pain relief at rest and fewer adverse effects at 24 hours, ISB provides better analgesia in the immediate postoperative period. For arthroscopic shoulder surgery, SSAX can be a clinically acceptable analgesic option with different analgesic profile compared with ISB. PMID- 27380106 TI - The Impact of Neuraxial Versus General Anesthesia on the Incidence of Postoperative Surgical Site Infections Following Knee or Hip Arthroplasty: A Meta Analysis. AB - BACKGROUND: Recent studies have yielded conflicting results on the association between anesthesia technique and incidence of postoperative surgical site infections (SSIs) after knee arthroplasty (KA) and hip arthroplasty (HA). Our group conducted a meta-analysis of all available studies to clarify this potential association. METHODS: Our group searched MEDLINE, EMBASE, and Google Scholar for all relevant studies (1990-2015) reporting on the association between anesthetic technique and SSI after KA or HA. Meta-analysis was performed to estimate both the pooled unadjusted odds ratio (OR) and adjusted OR (aOR) using a random-effects model. Subgroup analyses and metaregression were conducted to explore potential sources of heterogeneity and bias. RESULTS: Of the initial 435 records, 13 studies (n = 362,029) met the inclusion criteria. The use of neuraxial anesthesia was associated with a significant reduction in incidence of postoperative SSI as compared with general anesthesia for all arthroplasties based on unadjusted (OR, 0.77; 95% confidence interval [CI], 0.70-0.86; P < 0.001) and adjusted (aOR = 0.84; 95% CI, 0.76-0.92; P < 0.001) data. Subgroup analyses showed similar reductions in incidence of postoperative SSI for KA (OR = 0.75; 95% CI, 0.68-0.84; P < 0.001; aOR = 0.85; 95% CI, 0.79-0.92; P < 0.001) and HA (OR = 0.79; 95% CI, 0.65 to 0.95; P = 0.02; aOR = 0.84; 95% CI, 0.71-1.00; P = 0.057). CONCLUSIONS: Synthesis of the existing evidence supports the overall beneficial effects of neuraxial anesthesia in decreasing the development of SSI after joint arthroplasty (KA and HA). Given the limitations associated with interpretation of data from large observational trials, further investigation using prospective randomized trial design is warranted in this promising area. PMID- 27380107 TI - Combined Spinal Epidural Technique for Labor Analgesia Does Not Delay Recognition of Epidural Catheter Failures: A Single-center Retrospective Cohort Survival Analysis. AB - BACKGROUND: It is unclear whether recognition of epidural catheter failures is delayed with combined spinal epidural technique (CSE) compared to traditional epidural technique (EPID) when used for labor analgesia. The authors hypothesized that recognition of failed catheters is not delayed by CSE. METHODS: Anesthetic, obstetric, and quality assurance records from 2,395 labor neuraxial procedures (1,440 CSE and 955 EPID) performed at Forsyth Medical Center (Winston-Salem, North Carolina) between June 30 and December 31, 2012, were retrospectively analyzed. The primary outcome was catheter survival (failure-free) time during labor analgesia. A proportional hazards model with the counting method was used to assess relationships between the techniques and survival (failure-free) time of catheters, while controlling for subjects' body mass index and providers' level of training in the final best-fit multivariable regression model. RESULTS: Cumulative incidence of epidural catheter failures was 6.6% for CSE and 11.6% for EPID (P = 0.001). In the multivariable regression model, catheters placed with CSE versus epidural were less likely to fail (hazard ratio, 0.58; 95% CI, 0.43 to 0.79; P = 0.0002) for labor analgesia. Among the catheters that failed, there was no overall difference in failure time course between the techniques (hazard ratio, 1.17; 95% CI, 0.89 to 1.54; P = 0.26) even though more failed catheters with CSE (48.4%) than with EPID (30.6%) were recognized within the first 30 min of placement (P = 0.009). CONCLUSIONS: In this cohort, CSE has a significantly lower risk of overall epidural catheter failures than EPID and does not delay recognition of epidural catheter failures. Choice of CSE versus EPID should be based on overall risk of failure, efficacy, and side effects. PMID- 27380108 TI - Screening for streptomycin resistance conferring mutations in Mycobacterium tuberculosis isolates from Iran. AB - Point mutations in the rpsL and rrs genes can lead to development of streptomycin (STR) resistance in Mycobacterium tuberculosis. The aims of this study were to determine the frequency of mutations in STR resistant M. tuberculosis isolates in Iran and to analyze the possible relationship between bacterial genotype and STR resistance. Twenty-three M. tuberculosis samples comprising 9 multidrug-resistant (MDR) and 14 non-MDR isolates, recovered from TB patients in four regions: Tehran (n = 14), Isfahan (n = 2), Zahedan (n = 2), and Khorasan (n = 5), were analysed. Mutational profiling was performed by sequencing of the rrs and rpsL genes and spoligotyping method was used for genotyping. Nineteen isolates were resistant to STR, among them 7 exhibited mutations in the rpsL gene and 7 had mutations in the rrs gene. The remaining 5 STR resistant as well as all susceptible isolates lacked any mutation in both genes. Beijing genotype was associated with both MDR and STR resistance in which all mutations occurred at codon 43 of the rpsL gene. There was an association between mutations in the rpsL and rrs genes and STR resistance. We also found a correlation between Beijing genotype and STR resistance. PMID- 27380109 TI - Influence of elective and emergency cesarean delivery on mother emotions and bonding. AB - BACKGROUND: Previous studies have indicated that mode of delivery could have a negative effect on bonding. AIMS: To assess feelings towards newborn infants in mothers who delivered by cesarean delivery, elective (ElCD) or emergency (EmCD). STUDY DESIGN: This observational prospective study took place at the Division of Perinatal Medicine, Policlinico Abano Terme, Abano Terme, Italy, from September 2014 to April 2015. SUBJECTS: The sample included 573 puerperae divided into three groups: women undergone ElCD (n=73; 12.73%), women undergone EmCD (n=81; 14.13%) and women who underwent vaginal delivery (VD) (n=419; 73.12%). OUTCOME MEASURES: The instrument used was the Mother-to-Infant Bonding Scale (MIBS; Taylor et al., 2005), a self-report test to measure mother's feelings towards her baby. High scores indicate worse mother-to-infant bonding and a score>=2, established as cut-off, indicates an altered bonding. RESULTS: The mean MIBS global score was 0.50+/-1.05 in the VD mothers, 0.67 (+/-1.14) for ElCD mothers and 0.92 (+/-1.05) for EmCD mothers, resulting significantly higher in EmCD mothers (p<0.001). The percentage of altered bonding (Score>=2) in the three groups was of 11.21% (n=47) in VD, 17.80% (n=13) in ElCD and 23.45% (n=19) in EmCD, significantly higher in EmCD women (p<0.006). In addition, EmCD mothers scored significantly higher Joyful (0.074+/-0.26 vs 0.185+/-0.39; p<0.005) and Disappointed (0.063+/-0.25 vs 0.123+/-0.36; p<0.008) subscales. CONCLUSIONS: It was found that EmCD negatively affects mother bonding and opening emotions, and originates in mother feelings like sadness and disappointment for the unplanned delivery evolution. PMID- 27380110 TI - Emerging biomarkers in systemic sclerosis. AB - PURPOSE OF REVIEW: The severity of each organ involvement, natural course, and response to therapies are extremely heterogeneous among patients with systemic sclerosis (SSc). The discovery and validation of biomarkers can help identify disease risk, improve early diagnosis and prognosis, better design clinical trials and assess response to treatment, and further elucidate the underlying pathogenic mechanisms of this disease. The goal of this review is to summarize recent advances into the field of SSc biomarker development. RECENT FINDINGS: The use of both traditional and next-generation techniques, including large-scale transcriptomic, epigenomic, and proteomic technologies, has yielded a slew of new candidate biomarkers that correlate with different SSc clinical phenotypes. Recent evidence indicates that skin gene expression-based pharmacodynamic biomarkers have the potential to be employed as surrogate measures of clinical endpoints (i.e. modified Rodnan skin thickness score) providing objective assessment of response in clinical trials. SUMMARY: Several promising biomarkers addressing key unmet needs related to the evaluation and management of SSc patients have been recently proposed. Nevertheless, these biomarkers still require rigorous validation in prospective studies and have yet to make their way into clinical practice and therapeutic development. Robust biomarkers, ideally mechanistic ones, are needed to enable precision medicine in SSc. PMID- 27380111 TI - Comment on Ersan et al.'s "Evaluation of Macular Ganglion Cell-inner Plexiform Layer and Choroid in Psoriasis Patients Using Enhanced Depth Imaging Spectral Domain Optical Coherence Tomography". PMID- 27380112 TI - Presence of histological regression as a prognostic factor in cutaneous melanoma patients. AB - Regression is caused by a host immunological response primarily characterized by lymphocytic infiltration directed against melanoma cells. The prognostic significance of regression remains controversial in cutaneous melanoma patients. The aim of this study was to determine the clinical significance of the histological regression status in patients with cutaneous melanoma. A total of 664 patients with a pathologically confirmed cutaneous melanoma were enrolled into this study and were investigated retrospectively. The median age of the patients was 51 years, ranging in age from 16 to 104 years. The majority of them had lesions without regression (n=495; 74.5%) and others had lesions with regression (n=169; 25.5%). Melanoma patients with regression were more frequently males (60.1 vs 51.7%; P=0.038) and had axial localized lesions (67.5 vs 53.7%; P=0.002), superficial spreading histologic subtype (73.2 vs 49.1%; P=0.000), thin Breslow depth (<2 mm) (44.6 vs 33.5%; P=0.01), and the presence of tumor infiltrating lymphocytes (74.4 vs 60.0%; P=0.001) than those without regression. However, regression was not significantly associated with age, Clark level, mitotic rate, ulceration, vertical growth phase, neurotropism, lymphovascular invasion, nor association with a pre-existing melanocytic nevus. Similarly, no significant correlations were found between regression and lymph node involvement, recurrence, nor metastasis of disease. Patients with, nodular pathology, advanced Clark invasion level (IV-V), thick Breslow depth (>=2 mm), high mitotic rate (>3/mm), ulceration, vertical growth phase, neurotropism, lymphovascular invasion, lymph node involvement, metastasis, and recurrence of disease, and male patients had poor prognostic variables for both relapse-free survival and overall survival. However, the presence of regression was not associated with relapse-free survival (P=0.093) nor overall survival (P=0.113) similar to other factors such as age, tumor localization, tumor-infiltrating lymphocytes, and association with a pre-existing melanocytic nevus. Similar insignificant P values were also observed in multivariate analyses (P=0.115 and 0.816, respectively). In conclusion, the presence of histological regression plays no prognostic role in nodal involvement nor survival in patients with cutaneous melanoma. PMID- 27380113 TI - Fatty acid profiles of monofloral clover beebread and pollen and proteomics of red clover (Trifolium pratense) pollen. AB - Fatty acids were identified in monofloral beebread (BB) and bee pollen (BP) loads collected from Trifolium pratense L. A gas chromatography method was used to identify and quantify fatty acids: Thirty-five fatty acids were identified in BB and 42 in BP. A high amount of the healthy n-3 fatty acids was found. The ratio of polyunsaturated fatty acids n-3 to n-6 reached a value of 8.42 and 3.35 in the latter products. The proteomic analysis also was performed on the manually collected T. pratense pollen, and the most abundant protein groups were subjected to mass spectrometry analysis. Proteins identified in T. pratense pollen are involved in the main cellular functions (cell membrane formation, organelles traffic, and mainly metabolic processes). Because of the composition of fatty acids in BB and BP and a variety of proteins present in pollen, these products are considered to be favorable for human nutrition and health. PMID- 27380114 TI - Effect of ultrasound and heat on percutaneous absorption of l-ascorbic acid: human in vitro studies on Franz cell and Petri dish systems. AB - OBJECTIVE: Percutaneous absorption of l-ascorbic acid (LAA) is limited due to its high hydrophilicity and low stability. Here, we investigated the effect of post dosing sonophoresis (329 kHz, 20 mW cm-2 ) and heat (36 degrees C) on transdermal delivery of LAA. METHODS: Ultrasound/heat, heat and control treatments were applied on skin surface for 2 and 5 min after topical application of C14-labelled LAA aqueous solution. After 15 min post-exposure, radioactivity was measured in tape-striped stratum corneum (TS-SC), epidermis, dermis and receptor fluid. As Franz diffusion cell model may have different acoustic response than in vivo human tissues, a novel Petri dish model was developed and compared with Franz cell model on the effects of ultrasound/heat treatment on the skin permeability. RESULTS: Five-min ultrasound/heat treatment significantly accelerated skin absorption/penetration of LAA; 2-min treatment showed no enhancement effect on Franz diffusion cell model at the end of experiment. The use of Petri dish model significantly increased LAA concentrations in epidermis after 5 min of ultrasound/heat treatment, compared to the results of Franz cell model. CONCLUSION: Combination of ultrasound (329 kHz, 20 mW cm-2 ) and heat (36 degrees C) significantly enhanced LAA transdermal penetration, when the time of treatment was sufficient (5 min). As Petri dish model was designed to simulate acoustic respond of dense human tissue to ultrasound, the difference between Franz cell and Petri dish models suggests that the enhancement effect of ultrasound/heat on skin penetration in vivo may be greater than that determined on in vitro Franz cell model. PMID- 27380115 TI - Stress-Strain Relationships in Hydroxyl Substituted Polyethylene. AB - Stress-strain relationships in semicrystalline hydroxylated polyethylene are studied using all-atom molecular dynamics simulations. Chain sizes ranging from 50 to 2000 carbons are gradually cooled from melt in order to obtain semicrystalline samples for pure, 4%, and 8% hydroxylated chains. Local orientational order of the polymer backbone and hydrogen bonding behavior is studied. The effects of -OH substitution and chain length on stress-strain relationships are examined at 300 K. The number of hydrogen bonds is found to be independent of the chain length. Stress-strain relationships are generally unaffected by 4% hydroxyl substitution in long chain polyethylene. The presence of 8% -OH tends to increase the elastic limit of the material. A method for comparing semicrystalline samples of substituted and unsubstituted polymeric chains is presented by eliminating differences in alignment, distribution, and extent of crystallization. PMID- 27380116 TI - The Use of Dermal Regeneration Template (Matriderm(r) 1 mm) for Reconstruction of a Large Full-Thickness Scalp and Calvaria Exposure. PMID- 27380117 TI - Clinical and Histopathological Features of Post Burn Pruritus. AB - The aim of the study was to evaluate the clinical and histopathological characteristics of patients with post burn pruritus. The authors took skin samples from 62 burn patients with or without pruritus. The measured skin condition includes thickness and paresthesia. Various clinical features were rated on patient assessment scale (PSAS) and observer scar assessment scale. The samples were stained with hematoxylin & eosin, Masson's trichrome, Verhoeff's elastic, and toluidine blue stain. The stained samples were analyzed in terms of epidermal thickness, mononuclear cell infiltration, collagen bundles, elastic fibers, and mast cell distribution. A total of 62 patients were divided into group A (43 patients with pruritus) and group B (19 patients without). The mean (+/-SD) intensity of itch in group A patients was 4.58 (+/-3.24). Group A patients had thickened epidermises and higher scores on the PSAS and observer scar assessment scale, especially on the PSAS score. Sensations, including stinging and electric shock sensations, were more frequent in group A than in group B. Histological analysis revealed that group A patients had thinner collagen bundles and more increased mast cell counts, while others did not. Patients suffering from post burn pruritus had distinctive clinical and histopathological features, such as prominent mast cell deposition and thin collagen bundles, compared with group B patients. These results may help better understand post burn pruritus. PMID- 27380118 TI - An Examination of a Yoga Intervention With Pediatric Burn Survivors. AB - Burn injuries have a major influence on the survivors' physical and psychological functioning. In pediatric burns, the consequences persist long after the injury. The objective of this study is to evaluate an existing yoga kids program to gain better understanding of the physical and psychosocial effects of a yoga practice among children with burn injuries. Thirty campers participated in a series of four (1 hour) yoga sessions during the summer of 2014. Nationally trained Instructors had taught children's yoga in the Southwestern United States for at least 10 years. A Yoga Evaluation Questionnaire, designed for children, was used to evaluate perceptions of somatic and cognitive anxiety before and after each Yoga session. Camper's age ranged from 6 to 12 years old with burn severities ranging from 5 to 75%. A dependent samples t-test was used to test for differences between composite pre- and postintervention scores for both somatic and cognitive anxiety. Significant effects emerged for somatic anxiety t(29) = 4.24, P < .001, d = 0.77, and cognitive anxiety t(29) = -4.188, P < .001, d = 0.76. For both cognitive and somatic anxiety, the postintervention composite mean scores were significantly higher, indicating a decrease in somatic and cognitive anxiety. This study suggests that participation in a Yoga program may lower perceptions of cognitive and somatic anxiety in pediatric burn survivors. Further, Yoga is one technique that may compliment the short- and long-term treatment of burn injuries. PMID- 27380119 TI - Impact of Early Inpatient Rehabilitation on Adult Burn Survivors' Functional Outcomes and Resource Utilization. AB - On July 2012, a rehabilitation hospital merged with a trauma center where the regional burn center is located. That rehabilitation center provides the only burn rehabilitation program in our region. The objective of this study was to determine if earlier initiation of inpatient rehabilitation after merger had an effect on burn survivors' functional outcomes and resource utilization. A retrospective review of electronic data of burn survivors' functional outcomes (functional independence measure [FIM] ratings on admission, at discharge, and percent change), and resource utilization (waiting time for rehab, burn center length of stay [LOS], rehab LOS, physiotherapy and occupational therapy rehabilitation workload [RehabWorkload], and discharge destination) was undertaken. Adult burn survivors who required inpatient rehabilitation and were transferred from the burn center to the inpatient rehabilitation service before the merger (July 2010-June 2012) were compared with those transferred after the merger (July 2012-June 2014). One hundred thirty-eight burn survivors were transferred from the burn center to the inpatient rehabilitation service during the study period. Sixty (43.5%) were transferred before and 78 (56.5%) were transferred after the merger. There were 97 (70.3%) men and 41 (29.7%) women with a mean age of 47.9 +/- 17.9 years. TBSA burn was 24.2 +/- 16.9%, and full thickness burn was 13.1 +/- 16.4%. The etiology of these burns were flame (72.5%), scald (19.6%), electrical (5.1%), chemical (2.2%), and contact (0.7%). Patients in both groups had similar age, inhalation injury, TBSA, full thickness burn, FIM ratings, RehabWorkload, and burn etiology. Patients transferred before the merger had significantly more chemical burns (5% vs 0%, P = .046), and more work-related burns (26.7% vs 7.7%, P = .004). Patients transferred after the merger had significantly shorter burn center LOS (28.5 +/- 20.9 days vs 38.8 +/- 34.2 days, P = .043), and shorter waiting time for rehab (0.7 +/- 1.1 days vs 1.5 +/- 2.3 days, P = .010) than patients transferred before the merger. Early initiation of inpatient rehabilitation, after the burn center and the inpatient rehabilitation service were located in the same hospital, improved burn survivors' resource utilization. PMID- 27380120 TI - Marjolin's Ulcer in Chronic Hidradenitis Suppurativa: A Rare Complication of an Often Neglected Disease. AB - Hidradenitis suppurativa (HS) is a chronic, debilitating disease with definitive treatment consisting of wide surgical excision of all affected tissue. Originally described in burns, Marjolin's ulcer (MU) has been described in a variety of wound types, including hidradenitis. HS patients often have long delays to diagnosis and management of their chronic wounds, leading to increased risk of MU. A retrospective review of our burn database was performed from 2008 to 2014. Seventy-two consecutive patients taken to the operating room for HS were retrospectively evaluated for demographic data, number of excisions, total area of excised skin, need for skin grafting, pathology results, and outcome. Fifty eight percent of patients were male. Mean age was 36.88 +/- 13.52 years. Mean size of excision was 743.71 +/- 774.75 cm. Total number of operative procedures was 187, averaging 2.612 per patient, with 52% of patients undergoing skin grafting. Two patients had confirmed pathology of squamous cell carcinoma. Both were women with perineal HS and had metastatic disease on further workup. Both patients underwent chemotherapy and radiation with progression of their disease. The incidence of MU of 2.78% in this study is similar to the 2% incidence described historically in the burn population. All practitioners who treat HS patients should be aware of the devastating complication of MU arising in the chronic wound bed. We recommend that all excised tissue be sent to pathology for evaluation, and to consider early wide local excision of any chronically inflamed tissues to alleviate the risk of MU for this patient population. PMID- 27380121 TI - Measuring the Social Impact of Burns on Survivors. AB - Many burn survivors experience social challenges throughout their recovery. Measuring the social impact of a burn injury is important to identify opportunities for interventions. The aim of this study is to develop a pool of items addressing the social impact of burn injuries in adults to create a self reported computerized adaptive test based on item response theory. The authors conducted a comprehensive literature review to identify preexisting items in other self-reported measures and used data from focus groups to create new items. The authors classified items using a guiding conceptual framework on social participation. The authors conducted cognitive interviews with burn survivors to assess clarity and interpretation of each item. The authors evaluated an initial pool of 276 items with burn survivors and reduced this to 192 items after cognitive evaluation by experts and burn survivors. The items represent seven domains from the guiding conceptual model: work, recreation and leisure, relating to strangers, romantic, sexual, family, and informal relationships. Additional item content that crossed domains included using self-comfort and others' comfort with clothing, telling one's story, and sense of purpose. This study was designed to develop a large item pool based on a strong conceptual framework using grounded theory analysis with focus groups of burn survivors and their caregivers. The 192 items represent 7 domains and reflect the unique experience of burn survivors within these important areas of social participation. This work will lead to developing the Life Impact Burn Recovery Evaluation profile, a self reported outcome measure. PMID- 27380122 TI - Adult Contractures in Burn Injury: A Burn Model System National Database Study. AB - As the overall survival rate for burn injury has improved, increased emphasis is placed on postburn morbidity and the optimization of functional and cosmetic outcomes. One major cause of morbidity and functional deficits is that of joint contractures. The true incidence of postburn contractures and their associated risk factors remains unknown. This study examines the incidence and severity of contractures in a large, multicenter, burn population. The associated risk factors for the development of contractures are determined. Data from the National Institute on Disability and Rehabilitation Research Burn Model System database, for adult burn survivors from 1994 to 2003, were analyzed. Demographic and medical data were collected on each subject. The primary outcome measures included the presence of contractures, number of contractures per patient, and severity of contractures at each of nine locations (shoulder, elbow, hip, knee, ankle, wrist, neck, lumbar spine, and thoracic spine) at time of hospital discharge. Regression analysis was performed to determine predictors of the presence, severity, and numbers of contractures, with P < .05 used for statistical significance. Of the 1865 study patients, 620 (33%) developed at least 1 contracture at hospital discharge. Among those with at least one contracture, the mean is three (3.38) contractures per person. The shoulder was the most frequently contracted joint (23.0%), followed by the elbow (19.9%), wrist (17.3%), ankle (13.6%), and knee (13.4%). Most contractures were mild (47.2%) or moderate (32.9%) in severity. Statistically significant predictors of contracture development were male sex, black race, Hispanic ethnicity, medical problems, neuropathy, TBSA grafted, and TBSA burned. Predictors of the severity of contracture included male sex, black race, medical problems, neuropathy, TBSA grafted, and TBSA burned. Predictors of the number of contractures included male sex, medical problems, flash burn, neuropathy, TBSA burned, and TBSA grafted. Similar to a previous single-center study on postburn contractures, approximately one third of the patients with an eligible burn injury requiring autografting developed a contracture at hospital discharge. It is likely that these contractures develop despite early therapeutic interventions such as positioning and splinting; therefore, the challenge to the burn community remains, to identify new and better prevention strategies. PMID- 27380123 TI - Does Overestimation of Burn Size in Children Requiring Fluid Resuscitation Cause Any Harm? AB - Overestimation of burn size especially in children is common. It is unclear if this may cause harm. This study was designed to assess the accuracy of burn size estimation by referring non-burn clinicians and investigate whether inaccurate estimates caused any harm. Three and a half years retrospective review of pediatric resuscitation burns (ie, >=10% TBSA) referred to a tertiary burns center from other hospitals was performed. This included basic demographics, data from referring emergency departments (initial TBSA estimations and fluid volumes prescribed), and data on arrival to the burn center (actual burn TBSA sustained, fluid volumes given prior to arrival, and actual fluid volumes required). Clinical parameters at 8 and 24 hr after injury were also examined. Forty-six patients were identified. Mean age was 3.9 years and weight 18 kg. Mean time to arrival from initial burn injury to our tertiary center was 5 hr. Thirty-two children (70%) had their burns overestimated, seven (15%) underestimated, and another seven (15%) were correctly estimated. After accurate calculations of the burn size and the required resuscitation fluids on arrival to the burns center, only five children of the entire cohort of 46 patients (11%) had received more fluids than required. These five children were in the overestimated burn size group. Only three children received the appropriate amount of fluid prior to arrival to the burns center. There were no mortalities or significant clinical adverse events in any of the children. Overestimation led to overprescription of fluid volumes, but this did not translate into over-resuscitation, and in most cases was in fact associated with inadequate fluid administration. Although 70% of the children in our cohort had the burn size overestimated, only 11% had actually received more fluids than required before arrival. None of these children went on to have any significant complications as a result of overestimation. Training and education is essential for clinicians in emergency departments. However, estimation of size in pediatric burns, in particular scalds, is challenging and the importance of early transfer to a specialist service cannot be overemphasized. PMID- 27380124 TI - Treatment of Children With Scalds by Xenografts: Report From a Swedish Burn Centre. AB - Scalds are the most common type of burn in children, and one way to treat them is with xenografts with no topical antimicrobials in line with the recommendations of a recent review. However, this treatment has not been examined in detail. Our aim was to describe the treatment of such children when biological dressings (xenografts) were used without local antimicrobials. We reviewed the medical records of all children admitted to a Swedish National Burn Centre during the period 2010-2012 with scalds who were treated with xenografts. Percentage TBSA injured, age, length of hospital stay, number of operations, antibiotics given, duration of antibiotic treatment, and pain score during the first 3 days, application of xenografts, and clinical notes of wound infection were recorded. We studied 67 children, (43 of whom were boys), with a median (interquartile range [IQR]) age of 1 (1-2) year and median (IQR) TBSA% 6.2 (4-11). Twenty children (30%) required operation. Twelve (18%) developed a wound infection, 29 (43%) had other infections, and 26 (39%) were free from infection. The median (IQR) duration of systemic antibiotics was 10 (6-13) days. On the day that the xenografts were applied 10 of the children had a Face, Legs, Activity, Cry, and Consolability (FLACC) score between 3 and 7, and during the following 2 days, only four children scored in this range. The remaining 57 children had scores < 3 on the day that xenografts were applied and on the following 2 days. Median (IQR) length of stay/TBSA% was 0.7 (0.4-1.0). Treatment with xenografts was associated with median length of stay/TBSA% <1 and low pain scores. Despite a high rate of prescription of systemic antibiotics, most were for reasons other than wound infection. PMID- 27380125 TI - Incidence and Clinical Outcome of Hypophosphatemia in Pediatric Burn Patients. AB - The objective of this study is to investigate the factors associated with serum phosphate concentrations in severely burned children and whether hypophosphatemia is associated with outcome. Seventy-eight children with a total body surface area of 24% (6.0-68.5) were retrospectively analyzed for serum phosphate concentrations during the first 10 days of stay in the intensive care unit (ICU). The method of generalized estimating equations was used to evaluate the effect of the exposure variables for serum phosphate concentrations during the study period. Outcome variables were the probability of ICU discharge at 30 days and time on mechanical ventilation. Potential explanatory variables for clinical outcome were hypophosphatemia (serum phosphate <3.8 mg/dL for children <2 years and <3.5 mg/dL for older children), age, sex, percent total body surface area burn, inhalation injury, and severe sepsis and/or septic shock. Competing-risk analysis was applied to calculate the probability of ICU discharge at 30 days, and death was assumed as the competing event. The rate of hypophosphatemia was 79.5%. Serum phosphate concentrations were associated with C-reactive protein (coefficient: -0.63; 95% confidence interval [CI]: -0.96 to -0.30; P = .001). Hypophosphatemia was independently associated with a 68% decrease in the probability of ICU discharge at 30 days (subhazard ratio: -0.32; 95% CI: 0.20, 0.53; P = .001) and an increase of 2.9 days in mechanical ventilation (coefficient: 2.91; 95% CI: 1.16, 4.66; P = .001). Serum phosphate concentrations in pediatric burn patients are associated with the magnitude of inflammatory response. Hypophosphatemia is associated with decreased probability of ICU discharge and increased time on mechanical ventilation. PMID- 27380126 TI - Silver Nanoparticles Entering Soils via the Wastewater-Sludge-Soil Pathway Pose Low Risk to Plants but Elevated Cl Concentrations Increase Ag Bioavailability. AB - The widespread use of silver nanoparticles (Ag-NPs) results in their movement into wastewater treatment facilities and subsequently to agricultural soils via application of contaminated sludge. On-route, the chemical properties of Ag may change, and further alterations are possible upon entry to soil. In the present study, we examined the long-term stability and (bio)availability of Ag along the "wastewater-sludge-soil" pathway. Synchrotron-based X-ray absorption spectroscopy (XAS) revealed that ca. 99% of Ag added to the sludge reactors as either Ag-NPs or AgNO3 was retained in sludge, with >=79% of this being transformed to Ag2S, with the majority (>=87%) remaining in this form even after introduction to soils at various pH values and Cl concentrations for up to 400 days. Diffusive gradients in thin films (DGT), chemical extraction, and plant uptake experiments indicated that the potential (bio)availability of Ag in soil was low but increased markedly in soils with elevated Cl, likely due to the formation of soluble AgClx complexes in the soil solution. Although high Cl concentrations increased the bioavailability of Ag markedly, plant growth was not reduced in any treatment. Our results indicate that Ag-NPs entering soils through the wastewater sludge-soil pathway pose low risk to plants due to their conversion to Ag2S in the wastewater treatment process, although bioavailability may increase in saline soils or when irrigated with high-Cl water. PMID- 27380127 TI - Skin-transmitted pathogens and the heebie jeebies: evidence for a subclass of disgust stimuli that evoke a qualitatively unique emotional response. AB - Skin-transmitted pathogens have threatened humans since ancient times. We investigated whether skin-transmitted pathogens were a subclass of disgust stimuli that evoked an emotional response that was related to, but distinct from, disgust and fear. We labelled this response "the heebie jeebies". In Study 1, coding of 76 participants' experiences of disgust, fear, and the heebie jeebies showed that the heebie jeebies was elicited by unique stimuli which produced skin crawling sensations and an urge to protect the skin. In Experiment 2,350 participants' responses to skin-transmitted pathogen, fear-inducing, and disgust inducing vignettes showed that the vignettes elicited sensations and urges which loaded onto heebie jeebies, fear, and disgust factors, respectively. Experiment 3 largely replicated findings from Experiment 2 using video stimuli (178 participants). Results are consistent with the notion that skin-transmitted pathogens are a subclass of disgust stimuli which motivate behaviours that are functionally consistent with disgust yet qualitatively distinct. PMID- 27380128 TI - [Not Available]. PMID- 27380129 TI - [Not Available]. PMID- 27380131 TI - [Not Available]. PMID- 27380130 TI - [Not Available]. PMID- 27380132 TI - [Not Available]. PMID- 27380133 TI - [Not Available]. PMID- 27380134 TI - Sporadic colorectal cancer: microbial contributors to disease prevention, development and therapy. AB - The gut microbiota has been hailed as an accessory organ, with functions critical to the host including dietary metabolic activities and assistance in the development of a proper functioning immune system. However, an aberrant microbiota (dysbiosis) may influence disease processes such as colorectal cancer. In this review, we discuss recent advances in our understanding of the contributions of the microbiota to prevention, initiation/progression, and treatment of colorectal cancer, with a major focus on biofilms and the antimicrobial and antitumoural immune response. PMID- 27380135 TI - Repression of the autophagic response sensitises lung cancer cells to radiation and chemotherapy. AB - BACKGROUND: The cellular autophagic response to radiation is complex. Various cells and tissues respond differentially to radiation, depending on both the dose of exposure and the time post irradiation. In the current study, we determined the autophagosomal and lysosomal response to radiation in lung cancer cell lines by evaluating the expression of the associated proteins, as well as the effect of relevant gene silencing in radio and chemosensitisation. Furthermore, tumour sensitisation was evaluated in in vivo autophagic gene silencing model after irradiation. METHODS: A549 and H1299 cell lines were utilised as in vitro cancer models. Both cell lines were transfected with various small-interfering RNAs, silencing auto-lysosomal genes, and irradiated with 4 Gy. Cell growth response was evaluated with AlamarBlue assay. Western blot and confocal microscopy were utilised for the characterisation of the auto-lysosomal flux. Also, the H1299 cell line was stable transfected with small-hairpin RNA of the MAP1LC3A gene, and the tumour radiosensitisation in Athymic Nude-Foxn1(nu) was evaluated. RESULTS: Following exposure to 4 Gy of radiation, A549 cells exhibited a significant induction of the autophagic flux, which was not supported by transcriptional activation of auto-lysosomal genes (LC3A, LC3B, p62, TFEB and LAMP2a), resulting in aggresome accumulation. Recovery of transcriptional activity and autophagy efficacy occurred 7 days post irradiation. Alternatively, H1299 cells, a relatively radio-resistant cell line, sharply responded with an early (at 2 days) transcriptional activation of auto-lysosomal genes that sustained an effective autophagosomal flux, resulting in adequate aggresome clearance. Subsequently, we tested the silencing of four genes (LC3A, LC3B, TFEB and LAMP2a), confirming a significant radiosensitisation and chemosensitisation to various chemotherapeutic agents, including cisplatin and taxanes. In mouse xenografts, exposure to radiation significantly reduced tumour growth (P<0.001), which was exacerbated among shLC3A-H1299 transfected tumours. CONCLUSIONS: The ability of lung cancer cells to survive after irradiation at 4 Gy depends on their ability to sustain a functional autophagic flux. Abrogation of such ability results in increased radiosensitivity and susceptibility to various chemotherapy agents. Selective inhibitors of cancer cell autophagic function may prove important for the eradication of lung cancer. PMID- 27380136 TI - Definitive chemoradiation alters the immunologic landscape and immune checkpoints in head and neck cancer. AB - BACKGROUND: Preclinical and clinical studies suggest potential synergy between high dose per fraction focal radiation and immunotherapy. However, conventionally fractionated radiation regimens in combination with concurrent chemotherapy are more commonly administered to patients as definitive treatment and may have both immune-stimulating and -suppressive effects. METHODS: We prospectively collected longitudinal samples from head and neck squamous cell carcinoma patients receiving definitive radiation therapy. We quantified changes in populations of circulating immune cells and chemokines CXCL9, 10, and 16. Analyses of humoral and cellular immune responses were conducted in select patients via proteomic analysis and T-cell receptor sequencing. RESULTS: Treatment not only increased circulating CD-8+ T-effector cells, but also myeloid-derived suppressor cells, regulatory T cells, and checkpoint receptor-expressing T cells, particularly PD 1+ T cells. Significant decreases in CXCL10 and increases in CXLC16 were noted. Treatment also increased the percentage of unique and dominant TCR clones, and increased humoral responses as measured by proteomic array. CONCLUSIONS: Our results suggest that fractionated chemoradiation leads to quantifiable effects in circulating immune mediators, including a balance of stimulatory and suppressive mechanisms. These results suggest future combinations with immune checkpoint blockade. PMID- 27380138 TI - Chromosomal evolutionary dynamics of four multigene families in Coreidae and Pentatomidae (Heteroptera) true bugs. AB - Previous chromosome mapping of multigene families in Pentatomomorpha (Heteroptera) insects, which was restricted to the major rDNA, revealed remarkable conservation of number of clusters and chromosomal positions. Aiming to understand the chromosomal organization and evolutionary patterns of multigene families in karyotypes of Heteroptera, we performed a chromosomal mapping using four distinct multigene families in representatives of Coreidae (ten species) and Pentatomidae (five species). A single pair of the major rDNA cluster (18S rDNA probe) and a single pair of the minor rDNA cluster (5S rDNA probe), both terminally located were primarily observed, being, in most species, located in distinct chromosomes. However, some alternative patterns were also observed. In species in which the U2 snDNA and H4 gene clusters were mapped, they were mainly located in one autosomal pair each, wherein the H4 gene cluster was located in different positions. Our data suggest that the karyotype diversity reported in Coreidae is not reflected in the distribution diversity of multigene families. This contrasts with the data for Pentatomidae, with a conserved gross karyotype but a discrete diversity in the location of the clusters of multigene families, indicating genome dynamics for these markers. The findings are discussed to shed light on the possible causes for the conservation or variation observed and to assist in understanding the chromosomal evolutionary trends in the group. PMID- 27380137 TI - Assembly and Immunological Processing of Polyelectrolyte Multilayers Composed of Antigens and Adjuvants. AB - While biomaterials provide a platform to control the delivery of vaccines, the recently discovered intrinsic inflammatory characteristics of many polymeric carriers can also complicate rational design because the carrier itself can alter the response to other vaccine components. To address this challenge, we recently developed immune-polyelectrolyte multilayer (iPEMs) capsules electrostatically assembled entirely from peptide antigen and molecular adjuvants. Here, we use iPEMs built from SIINFEKL model antigen and polyIC, a stimulatory toll-like receptor agonist, to investigate the impact of pH on iPEM assembly, the processing and interactions of each iPEM component with primary immune cells, and the role of these interactions during antigen-specific T cell responses in coculture and mice. We discovered that iPEM assembly is pH dependent with respect to both the antigen and adjuvant component. Controlling the pH also allows tuning of the relative loading of SIINFEKL and polyIC in iPEM capsules. During in vitro studies with primary dendritic cells (DCs), iPEM capsules ensure that greater than 95% of cells containing at least one signal (i.e., antigen, adjuvant) also contained the other signal. This codelivery leads to DC maturation and SIINFEKL presentation via the MHC-I antigen presentation pathway, resulting in antigen specific T cell proliferation and pro-inflammatory cytokine secretion. In mice, iPEM capsules potently expand antigen-specific T cells compared with equivalent admixed formulations. Of note, these enhancements become more pronounced with successive booster injections, suggesting that iPEMs functionally improve memory recall response. Together our results reveal some of the features that can be tuned to modulate the properties of iPEM capsules, and how these modular vaccine structures can be used to enhance interactions with immune cells in vitro and in mice. PMID- 27380140 TI - Role of Sirtuins in Maintenance of Genomic Stability: Relevance to Cancer and Healthy Aging. AB - Genomic instability and epigenetic alterations are distinct hallmarks shared by cancer and aging. Sirtuins (SIRTs) are class III histone deacetylases that regulate gene expression in response to cellular metabolic status. SIRTs can modulate chromatin function through direct deacetylation of histones and by promoting altered methylation of histones and DNA, leading to repression of transcription. They can also interact and deacetylate a broad range of transcription factors and coregulators, thereby regulating target gene expression both positively and negatively. SIRT inhibition may be beneficial in decreasing the risk of some cancers, while SIRT activation can exert positive antiaging effects and help prevent age-related disease and cancers. Thus, SIRT modulation may positively affect the treatment of cancer and age-related disorders. In this study, we review emerging data on the effects of SIRTs as important regulators of genomic stability and explain the biological roles of SIRTs in cancer and aging. PMID- 27380139 TI - Quantitative trait loci identification and meta-analysis for rice panicle-related traits. AB - Rice yield is a complex trait controlled by quantitative trait loci (QTLs). In the past three decades, thousands of QTLs for rice yield traits have been detected, but only a very small percentage has been cloned to date, as identifying the QTL genes requires a substantial investment of time and money. Meta-analysis provides a simple, reliable, and economical method for integrating information from multiple QTL studies across various environmental and genetic backgrounds, detecting consistent QTLs powerfully and estimating their genetic positions precisely. In this study, we aimed to locate consistent QTL regions associated with rice panicle traits by applying a genome-wide QTL meta-analysis approach. We first conducted a QTL analysis of 5 rice panicle traits using 172 plants in 2011 and 138 plants in 2012 from an F2 population derived from a cross between Nipponbare and H71D rice cultivators. A total of 54 QTLs were detected, and these were combined with 1085 QTLs collected from 82 previous studies to perform a meta-analysis using BioMercator v4.2. The integration of 82 maps resulted in a consensus map with 6970 markers and a total map length of 1823.1 centimorgan (cM), on which 837 QTLs were projected. These QTLs were then integrated into 87 meta-quantitative trait loci (MQTLs) by meta-analysis, and the 95 % confidence intervals (CI) of them were smaller than the mean value of the original QTLs. Also, 30 MQTLs covered 47 of the 54 QTLs detected from the cross between Nipponbare and H71D in this study. Among them, the two major and stable QTLs, spp10.1 and sd10.1, were found to be included in MQTL10.4. The three other major QTLs, pl3.1, sb2.1, and sb10.1, were included in MQTL3.3, MQTL2.2, and MQTL10.3, respectively. A total of 21 of the 87 MQTLs' phenotypic variation were >20 %. In total, 24 candidate genes were found in 15 MQTLs that spanned physical intervals <0.2 Mb, including genes that have been cloned previously, e.g., EP3, LP, MIP1, HTD1, DSH1, and OsPNH1. However, it would be beneficial to identify a greater number of candidate genes from these MQTLs. Mining new genes that modulate yield and its related traits would assist researchers to better understand the relevant molecular mechanisms. The MQTLs found in this study that have small physical and genetic intervals are useful not only for marker-assisted selection and pyramiding, but they also provide important information of rice yield and related gene mining for future research. PMID- 27380141 TI - In vivo kinematic study of the tarsal joints complex based on fluoroscopic 3D-2D registration technique. AB - The tarsal bones articulate with each other and demonstrate complicated kinematic characteristics. The in vivo motions of these tarsal joints during normal gait are still unclear. Seven healthy subjects were recruited and fourteen feet in total were tested in the current study. Three dimensional models of the tarsal bones were first created using CT scanning. Corresponding local 3D coordinate systems of each tarsal bone was subsequently established for 6DOF motion decompositions. The fluoroscopy system captured the lateral fluoroscopic images of the targeted tarsal region whilst the subject was walking. Seven key pose images during the stance phase were selected and 3D to 2D bone model registrations were performed on each image to determine joint positions. The 6DOF motions of each tarsal joint during gait were then obtained by connecting these positions together. The TNJ (talo-navicular joint) exhibited the largest ROMs (range of motion) on all rotational directions with 7.39+/-2.75 degrees of dorsi/plantarflexion, 21.12+/-4.68 degrees of inversion/eversion, and 16.11+/ 4.44 degrees of internal/external rotation. From heel strike to midstance, the TNJ, STJ (subtalar joint), and CCJ (calcaneao-cuboid joint) were associated with 5.97 degrees , 5.04 degrees , and 3.93 degrees of dorsiflexion; 15.46 degrees , 8.21 degrees , and 5.82 degrees of eversion; and 9.75 degrees , 7.6 degrees , and 4.99 degrees of external rotation, respectively. Likewise, from midstance to heel off, the TNJ, STJ, and CCJ were associated with 6.39, 6.19 degrees , and 4.47 degrees of plantarflexion; 18.57 degrees , 11.86 degrees , and 6.32 degrees of inversion and 13.95 degrees , 9.66 degrees , and 7.58 degrees of internal rotation, respectively. In conclusion, among the tarsal joints, the TNJ exhibited the greatest rotational mobility. Synchronous and homodromous rotational motions were detected for TNJ, STJ, and CCJ during the stance phase. PMID- 27380143 TI - Transformation Optics: A Time- and Frequency-Domain Analysis of Electron-Energy Loss Spectroscopy. AB - Electron energy loss spectroscopy (EELS) and cathodoluminescence (CL) play a pivotal role in many of the cutting edge experiments in plasmonics. EELS and CL experiments are usually supported by numerical simulations, which-though accurate may not provide as much physical insight as analytical calculations do. Fully analytical solutions to EELS and CL systems in plasmonics are rare and difficult to obtain. This paper aims to narrow this gap by introducing a new method based on transformation optics that allows to calculate the quasistatic frequency- and time-domain response of plasmonic particles under electron beam excitation. We study a nonconcentric annulus (and ellipse in the Supporting Information ) as an example. PMID- 27380142 TI - Caldoramide, a Modified Pentapeptide from the Marine Cyanobacterium Caldora penicillata. AB - The isolation, structure determination, and biological activities of a new linear pentapeptide, caldoramide (5), from the marine cyanobacterium Caldora penicillata from Florida are described. Caldoramide (5) has structural similarities to belamide A (4), dolastatin 10 (1), and dolastatin 15 (2). We profiled caldoramide against parental HCT116 colorectal cancer cells and isogenic cells lacking oncogenic KRAS or hypoxia-inducible factors 1alpha (HIF-1alpha) and 2alpha (HIF 2alpha). Caldoramide (5) showed differential cytotoxicity for cells containing both oncogenic KRAS and HIF over the corresponding knockout cells. LCMS dereplication indicated the presence of caldoramide (5) in a subset of C. penicillata samples. PMID- 27380144 TI - Cationic DOPC-Detergent Conjugates for Safe and Efficient in Vitro and in Vivo Nucleic Acid Delivery. AB - The ability of a nonviral nucleic acid carrier to deliver its cargo to cells with low associated toxicity is a critical issue for clinical applications of gene therapy. We describe biodegradable cationic DOPC-C12 E4 conjugates in which transfection efficiency is based on a Trojan horse strategy. In situ production of the detergent compound C12 E4 through conjugate hydrolysis within the acidic endosome compartment was expected to promote endosome membrane destabilization and subsequent release of the lipoplexes into cytosol. The transfection efficiency of the conjugates has been assessed in vitro, and associated cytotoxicity was determined. Cellular uptake and intracellular distribution of the lipoplexes have been investigated. The results show that direct conjugation of DOPC with C12 E4 produces a versatile carrier that can deliver both DNA and siRNA to cells in vitro with high efficiency and low cytotoxicity. SAR studies suggest that this compound might represent a reasonable compromise between the membrane activity of the released detergent and susceptibility of the conjugate to degradation enzymes in vitro. Although biodegradability of the conjugates had low impact on carrier efficiency in vitro, it proved critical in vivo. Significant improvement of transgene expression was obtained in the mouse lung tuning biodegradability of the carrier. Importantly, this also allowed reduction of the inflammatory response that invariably characterizes cationic-lipid mediated gene transfer in animals. PMID- 27380145 TI - Ultra-Stretchable and Force-Sensitive Hydrogels Reinforced with Chitosan Microspheres Embedded in Polymer Networks. AB - An ultra-stretchable and force-sensitive hydrogel with surface self-wrinkling microstructure is demonstrated by in situ synthesizing polyacrylamide (PAAm) and polyaniline (PANI) in closely packed swollen chitosan microspheres, exhibiting ultra-stretchability (>600%), high sensitivity (0.35 kPa-1 ) for subtle pressures (<1 kPa), and can detect force in a broad range (102 Pa-101 MPa) with excellent electrical stability and rapid response speed, potentially finding applications for E-skin. PMID- 27380146 TI - Strategies for Success-What Does It Really Take? PMID- 27380147 TI - Retraction of: A Novel Approach to Telemedicine Video Control Technology, by Dinevski D. and Pacnik G. Telemed J E Health. 2009;15(9):859-866. DOI: 10.1089/tmj.2009.0025. PMID- 27380148 TI - Hyperthermia-driven aberrations of secreted microRNAs in breast cancer in vitro. AB - PURPOSE: Expression profile alterations of nine breast cancer (BC)-associated secreted microRNAs (miRs) were determined under microenvironmental alterations occurring in tumour progression, metastasis or specific oncological treatment modalities. Thereto, the potential influence of the exogenic stimuli hypoxia, acidosis and hyperthermia was investigated in vitro. MATERIAL AND METHODS: Four established BC cell lines were applied as in vitro BC model systems. Quantitative analyses of secreted microRNA specimens were performed by RNA isolation from cell culture supernatant and subsequent real-time PCR in cells under physiological versus hypoxic, acidic or hyperthermia conditions. RESULTS: The in vitro application of exogenic stimuli hypoxia, extracellular acidosis and hyperthermia caused heterogeneous expression alterations for the investigated secreted miRNA phenotypes. The majority of relevant exogenic stimuli-dependent microRNA expression alterations were restricted to single events displaying distinct cell type and stimulus dependent correlations only. Most remarkably, hyperthermia triggered a uniform significant down-regulatory effect on the expression levels of the three secreted microRNAs miR-10b, miR-15b and miR-139, respectively. The marked decrease in miR-10b and miR-15b levels was detectable in all four, while miR-139 was found significantly reduced in three out of four BC cell lines. CONCLUSION: Hyperthermia-dependent down-regulatory influence on three distinct BC related microRNAs in vitro generates translational aspects for clinical BC treatment, since the identified microRNAs miR-10b, miR-15b and miR-139 are known to have oncogenic as well as tumour suppressor functions in BC. However, an evaluation regarding the potential impact of microRNA-related hyperthermia dependent alterations for innovative BC treatment approaches demands further analysis including in vivo data. PMID- 27380149 TI - Culturally competent evidence-based behavioral health services for the transgender community: Progress and challenges. AB - The presence of individuals who identify as transgender has emerged into public awareness in the United States in recent years. Celebrities who publicly transition have expanded the national conversation about gender variation beyond gender and women's studies classrooms and certain specialty health and mental health services. This increased public visibility has been accompanied by increased visibility in the mental health literature, including the publishing of competencies or guidelines for working with clients who identify as transgender by various professional organizations. However, rapid societal changes and increased understanding of the experience of being transgender in our society means literature can rapidly become dated. This commentary identifies key points that will move forward professional competency, both of the field and of individual practitioners, in the provision of psychological services. Topics discussed include (1) how mental health has contributed to trans stigma, (2) why more than good intentions are needed, (3) a research agenda for the development of high-quality evidence-based behavioral health care for the trans community, and (4) clinician recommendations. (PsycINFO Database Record PMID- 27380150 TI - Psychosocial, HIV, and health care management issues impacting transgender individuals. AB - This article reviews the varied process of transitioning and the psychosocial and quality-of-life benefits and outcomes of gender-affirmation therapeutic interventions, examines the barriers that transgender (TG) persons face in accessing health care, and describes the authors' experiences in improving access to medical services by launching a TG health care clinic and a service provider collaborative. It concludes with a summary of the burgeoning prevalence of HIV among TG people and the associated psychosocial effects. (PsycINFO Database Record PMID- 27380151 TI - The power of 41%: A glimpse into the life of a statistic. AB - "Forty-one percent?" the man said with anguish on his face as he addressed the author, clutching my handout. "We're talking about my granddaughter here." He was referring to the finding from the National Transgender Discrimination Survey (NTDS) that 41% of 6,450 respondents said they had attempted suicide at some point in their lives. The author had passed out the executive summary of the survey's findings during a panel discussion at a family conference to illustrate the critical importance of acceptance of transgender people. During the question and answer period, this gentleman rose to talk about his beloved 8-year-old granddaughter who was in the process of transitioning socially from male to female in her elementary school. The statistics that the author was citing were not just numbers to him; and he wanted strategies-effective ones-to keep his granddaughter alive and thriving. The author has observed that the statistic about suicide attempts has, in essence, developed a life of its own. It has had several key audiences-academics and researchers, public policymakers, and members of the community, particularly transgender people and our families. This article explores some of the key takeaways from the survey and the ways in which the 41% statistic has affected conversations about the injustices transgender people face and the importance of family and societal acceptance. (PsycINFO Database Record PMID- 27380152 TI - Transgender health and well-being: Gains and opportunities in policy and law. AB - This article discusses gains and opportunities in policy and law in the United States related to transgender health and well-being. Topics include (1) how the bathroom myth has been used every time a trans nondiscrimination bill is considered, (2) transgender nondiscrimination laws and policies, (3) the expansion of gender discrimination, (4) strategies for promoting mental health and well-being among trans people, (5) policy developments supporting the mental health and well-being of trans people, and (6) opportunities for action. (PsycINFO Database Record PMID- 27380153 TI - Family first: Community-based supports for refugees. AB - This article presents a community-based approach that targets family interventions and services through a preventive, family systems ecological framework. A public health approach is used to emphasize the need for a tiered model of family support that builds on the strengths of refugee families while recognizing their specific needs and challenges. The rationale for a family systems ecological perspective is presented to highlight the critical features of effective family support programs for refugee families, followed by a discussion regarding the transitions and adaptation faced by refugee families when entering the United States. Finally, a public-health problem solving model is employed to promote a comprehensive vision for how more effective support can be developed to best serve the mental health needs of refugee families. An integrated case example highlighting the Somali Parent Program, a family-focused intervention, is also provided. (PsycINFO Database Record PMID- 27380154 TI - Outcomes of Basic Versus Advanced Life Support for Out-of-Hospital Medical Emergencies. PMID- 27380155 TI - Outcomes of Basic Versus Advanced Life Support for Out-of-Hospital Medical Emergencies. PMID- 27380156 TI - Outcomes of Basic Versus Advanced Life Support for Out-of-Hospital Medical Emergencies. PMID- 27380157 TI - Is Prehospital Advanced Life Support Harmful? PMID- 27380158 TI - Why Physicians Hate "Patient Satisfaction": The Real Reasons. PMID- 27380159 TI - Accuracy of Peripheral Thermometers for Estimating Temperature. PMID- 27380160 TI - Accuracy of Peripheral Thermometers for Estimating Temperature. PMID- 27380161 TI - Content, Consistency, and Quality of Black Box Warnings. PMID- 27380162 TI - Web Exclusives. Annals Graphic Medicine - The Price of Progress. PMID- 27380163 TI - In-depth structural characterization of Kadcyla(r) (ado-trastuzumab emtansine) and its biosimilar candidate. AB - ASBTRACT The biopharmaceutical industry has become increasingly focused on developing biosimilars as less expensive therapeutic products. As a consequence, the regulatory approval of 2 antibody-drug conjugates (ADCs), Kadcyla(r) and Adcetris(r) has led to the development of biosimilar versions by companies located worldwide. Because of the increased complexity of ADC samples that results from the heterogeneity of conjugation, it is imperative that close attention be paid to the critical quality attributes (CQAs) that stem from the conjugation process during ADC biosimilar development process. A combination of physicochemical, immunological, and biological methods are warranted in order to demonstrate the identity, purity, concentration, and activity (potency or strength) of ADC samples. As described here, we performed extensive characterization of a lysine conjugated ADC, ado-trastuzumab emtansine, and compared its CQAs between the reference product (Kadcyla(r)) and a candidate biosimilar. Primary amino acid sequences, drug-to-antibody ratios (DARs), conjugation sites and site occupancy data were acquired and compared by LC/MS methods. Furthermore, thermal stability, free drug content, and impurities were analyzed to further determine the comparability of the 2 ADCs. Finally, biological activities were compared between Kadcyla(r) and biosimilar ADCs using a cytotoxic activity assay and a HER2 binding assay. The in-depth characterization helps to establish product CQAs, and is vital for ADC biosimilars development to ensure their comparability with the reference product, as well as product safety. PMID- 27380164 TI - Expression, purification, crystallization, and diffraction analysis of a selenomethionyl lipase Lip8 from Yarrowia lipolytica. AB - Yarrowia lipolytica is a nonconventional model micro-organism with multiple biotechnological applications. It is also considered to be an excellent producer for lipase. Genome survey shows that Y. lipolytica possesses various paralogs of genes coding for extracellular, cell-bound, and intracellular lipolytic enzymes. However, little structural information on these isoenzymes is available. With the aim to facilitate crystal structure solution of Lip8, one of the most valuable lipases from Y. lipolytica, a less conventional protein expression technique selenomethionyl protein expression was used to produce recombinant selenomethionine (SeMet)-Lip8 in Escherichia coli. Finally, three Met residues of Lip8 were all substituted with SeMet. A total of 72 mg of SeMet-Lip8 was obtained from a liter of the SeMet medium. Using sodium acetate as a precipitant and ammonium sulfate as an additive, crystals of the SeMet-Lip8 with 1.9 A were successfully cultured through hanging-drop vapor diffusion method. The estimated crystal dimensions were 0.11 * 0.11 * 0.14 mm2. The crystal belonged to the space group I4 with unit cell parameters a = b = 128.87 A, c = 171.77 A, alpha = beta = gamma = 90 degrees . It is the second member of lipase crystal family from Y. lipolytica. This work will provide a platform for further studying lipases from a structural insight. PMID- 27380165 TI - Correction: A Quasi-Steady Lifting Line Theory for Insect-Like Hovering Flight. AB - [This corrects the article DOI: 10.1371/journal.pone.0134972.]. PMID- 27380166 TI - Erratum to: UDP-glucuronosyltransferase 1A1*6 and *28 polymorphisms as indicators of initial dose level of irinotecan to reduce risk of neutropenia in patients receiving FOLFIRI for colorectal cancer. PMID- 27380167 TI - Analysis of positron emission tomography/computed tomography in patients to differentiate between malignant transformation of endometrioma and endometrioma. AB - PURPOSE: Of those patients who undergo open surgery for a suspicion of malignant transformation of endometrioma (MTOE) due to solid nodule enhancement identified by contrast-enhanced magnetic resonance imaging (MRI), some benign endometrioma cases are included. The aim of this retrospective study was to determine the value and diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) using 18-fluoro-2-deoxy-D-glucose (FDG) to differentiate between MTOE and endometrioma. PATIENTS AND METHODS: We retrospectively analyzed 1599 consecutive patients who underwent laparoscopic surgery for the diagnosis of endometrioma preoperatively and 31 patients who underwent open surgery for a suspicion of MTOE preoperatively from January 2003 to December 2011. We analyzed the age, serum CA125 levels, and MRI findings of the patients and calculated the optimal cut-off value for PET/CT using receiver operating characteristic curve analysis. RESULTS: Of the 1,599 patients who underwent laparoscopic surgery for a suspicion of endometrioma preoperatively, malignancy was identified in one (0.062 %) patient. Of the 31 patients who underwent open surgery for a suspicion of MTOE preoperatively, 11 were diagnosed with endometrioma (false positive group) and 20 with MTOE stage I (positive group). Age, tumor size, presence of shading on MRI and maximum standardized uptake values (SUVmax) on PET/CT were significantly different between the two groups. A SUVmax cut-off >4.0 is capable of excluding endometrioma cases, with 75 % sensitivity and 100 % specificity (area under the curve 90 %). CONCLUSION: PET/CT is a good diagnostic tool for MTOE using the optimal SUVmax cut-off of 4.0 (75 % sensitivity and 100 % specificity). PMID- 27380168 TI - Intrathoracic extensive-stage small cell lung cancer: assessment of the benefit of thoracic and brain radiotherapy using the SEER database. AB - BACKGROUND: Extensive-stage small cell lung cancer (ESCLC) includes metastatic disease and locally advanced disease confined to the thorax that cannot be encompassed in a typical radiation portal. We assessed and then compared the benefits of thoracic radiotherapy (TRT) and/or brain radiotherapy (BRT) on overall survival (OS) between the intrathoracic (T-ESCLC) and metastatic (M ESCLC) groups using the Surveillance Epidemiology and End Results database. METHODS: TRT and BRT data were available for 10150 patients treated from 1988 1997. The T-ESCLC group included 1774 patients. The Kaplan-Meier method was used to estimate OS and the proportional hazards model was used to estimate OS hazard ratios for prognostic factors including age, gender, race, tumor size, T/N stage, TRT, and BRT. RESULTS: The 2-year OS for T-ESCLC was 7.8 % compared to 3 % in the M-ESCLC group (p < 0.001). In the T-ESCLC group, TRT and BRT were delivered to 750 and 102 patients, respectively. The 2-year OS was 13 % in the TRT group compared to 4.1 % in the no-TRT group (p <= 0.001) and 22.5 % in the BRT group compared to 7 % in the no-BRT group (p < 0.001). In the M-ESCLC group, TRT and BRT were delivered to 3093 and 1887 patients, respectively. The 2-year OS was 4.4 % in the TRT group compared to 2.8 % in the no-TRT group (p < 0.001) and 4.3 % in the BRT compared to 2.6 % in the no-BRT group (p < 0.001). Age, gender, TRT and BRT were significant OS prognostic factors in both groups. CONCLUSIONS: Our study suggests that T-ESCLC is a disease entity distinct from M-ESCLC. Prospective studies to determine whether TRT should be recommended for the thoracic-only subgroup are warranted. PMID- 27380169 TI - Neoadjuvant chemotherapy with docetaxel and carboplatin followed by radical hysterectomy for stage IB2, IIA2, and IIB patients with non-squamous cell carcinoma of the uterine cervix. AB - BACKGROUND: We conducted a phase II study to evaluate the efficacy of neoadjuvant chemotherapy with docetaxel and carboplatin followed by radical hysterectomy for patients with non-squamous cell carcinoma of the uterine cervix. METHODS: Sixty one patients with International Federation of Gynecology and Obstetrics stage IB2, IIA2, or IIB non-squamous cell carcinoma of the uterine cervix were enrolled. The patients were administered docetaxel at a dose of 60 mg/m2, followed by carboplatin at a dose based on an area under the curve of 6. The treatments were repeated every 21 days for one to three cycles. Fifty-two patients were eligible to evaluate the efficacy of neoadjuvant chemotherapy followed by radical hysterectomy. Adverse events were evaluated in 59 patients. RESULTS: The response rate was 69 % (95 % CI, 57-82 %), with 5 patients achieving complete response, 31 partial response, 15 stable disease, and 1 progressive disease. Median follow-up duration was 1913 days with a range of 145-2632 days. Of 52 patients, 50 underwent radical hysterectomy after neoadjuvant chemotherapy. The 2-year overall survival rate was 81.8 % for stage IB2, 85.7 % for stage IIA2, and 92.6 % for stage IIB. The most frequent grade 3 and 4 hematological toxicity was neutropenia, with 43 patients experiencing grade 4 and 11 with grade 3. The nonhematological toxicities were mainly grade 1 or 2 in severity. CONCLUSION: Neoadjuvant chemotherapy with docetaxel and carboplatin followed by radical hysterectomy may be a useful strategy for patients with non-squamous cell carcinoma of uterine cervix. PMID- 27380170 TI - Clinical features and treatment strategy for HPV-related oropharyngeal cancer. AB - Among head and neck squamous cell carcinoma (HNSCC), the incidence of oropharyngeal SCC (OPSCC) is increasing in contrast to carcinoma with origin in other subsites. Human papillomavirus (HPV) is now recognized as a significant risk factor of the carcinogenesis of OPSCC. The HPV-related OPSCC patients tend to be relatively young, less exposed to tobacco and alcohol, and have a relatively high socioeconomic status and education level, which is distinct from HPV-unrelated classical OPSCC. The neck metastases tend to be aggressive and cystic. The better response to treatment resulting in improved prognosis of HPV related OPSCC led to reconsidering the clinical staging and treatment approaches. Clinical trials of treatment deintensification to reduce the acute and late toxicity without compromising efficacy have been conducted. This review of HPV related OPSCC focuses on current and generally accepted facts regarding the biology, epidemiology, and therapeutic strategy of this new disease entity. PMID- 27380171 TI - Conformational Stability of the NH2-Terminal Propeptide of the Precursor of Pulmonary Surfactant Protein SP-B. AB - Assembly of pulmonary surfactant lipid-protein complexes depends on conformational changes coupled with proteolytic maturation of proSP-B, the precursor of pulmonary surfactant protein B (SP-B), along the surfactant biogenesis pathway in pneumocytes. Conformational destabilization of the N terminal propeptide of proSP-B (SP-BN) triggers exposure of the mature SP-B domain for insertion into surfactant lipids. We have studied the conformational stability during GdmCl- or urea-promoted unfolding of SP-BN with trp fluorescence and circular dichroism spectroscopies. Binding of the intermediate states to bis ANS suggests their molten globule-like character. DeltaG0H2O was ~ 12.7 kJ.mol-1 either with urea or GdmCl. None of the thermal transitions of SP-BN detected by CD correspond to protein unfolding. Differential scanning calorimetry of SP-BN evidenced two endothermic peaks involved in oligomer dissociation as confirmed with 2 M urea. Ionic strength was relevant since at 150 mM NaCl, the process originating the endotherm at the highest temperature was irreversible (Tm2 = 108.5 degrees C) with an activation energy of 703.8 kJ.mol-1. At 500 mM NaCl the process became reversible (Tm2 = 114.4 degrees C) and data were fitted to the Non two States model with two subpeaks. No free thiols in the propeptide could be titrated by DTNB with or without 5.7 M GdmCl, indicating disulfide bonds establishment. PMID- 27380172 TI - Methamphetamine Consumption Inhibits Pair Bonding and Hypothalamic Oxytocin in Prairie Voles. AB - Methamphetamine (MA) abuse has been linked to violence, risk-taking behaviors, decreased sexual inhibition, and criminal activity. It is important to understand mechanisms underlying these drug effects for prevention and treatment of MA associated social problems. Previous studies have demonstrated that experimenter administered amphetamine inhibits pair bonding and increases aggression in monogamous prairie voles. It is not currently known whether similar effects on social behaviors would be obtained under conditions during which the drug is voluntarily (actively) administered. The current study investigated whether MA drinking affects pair bonding and what neurocircuits are engaged. In Experiment 1, we exposed male and female voles to 4 days each of 20 and 40 mg/L MA under a continuous 2-bottle choice (2BC) procedure. Animals were housed either singly or in mesh-divided cages with a social partner. Voles consumed MA in a drinking solution, but MA drinking was not affected by either sex or housing condition. In Experiment 2, we investigated whether MA drinking disrupts social bonding by measuring aggression and partner preference formation following three consecutive days of 18-hour/day access to 100 mg/L MA in a 2BC procedure. Although aggression toward a novel opposite-sex animal was not affected by MA exposure, partner preference was inhibited in MA drinking animals. Experiment 3 examined whether alterations in hypothalamic neuropeptides provide a potential explanation for the inhibition of partner preference observed in Experiment 2. MA drinking led to significant decreases in oxytocin, but not vasopressin, in the paraventricular nucleus of the hypothalamus. These experiments are the first investigation into how voluntary pre-exposure to MA affects the development of social attachment in a socially monogamous species and identify potential neural circuits involved in these effects. PMID- 27380173 TI - Transforming Growth Factor-beta1 T869C Gene Polymorphism Is Associated with Acquired Sick Sinus Syndrome via Linking a Higher Serum Protein Level. AB - BACKGROUND: Familial sick sinus syndrome is associated with gene mutations and dysfunction of ion channels. In contrast, degenerative fibrosis of the sinus node tissue plays an important role in the pathogenesis of acquired sick sinus syndrome. There is a close relationship between transforming growth factor-beta1 mediated cardiac fibrosis and acquired arrhythmia. It is of interest to examine whether transforming growth factor-beta1 is involved in the pathogenesis of acquired sick sinus syndrome. METHODS: Overall, 110 patients with acquired SSS and 137 age/gender-matched controls were screened for transforming growth factor beta1 and cardiac sodium channel gene polymorphisms using gene sequencing or restriction fragment length polymorphism methods. An enzyme-linked immunosorbent assay was used to determine the serum level of transforming growth factor-beta1. RESULTS: Two transforming growth factor-beta1 gene polymorphisms (C-509T and T+869C) and one cardiac sodium channel gene polymorphism (H588R) have been identified. The C-dominant CC/CT genotype frequency of T869C was significantly higher in acquired sick sinus syndrome patients than in controls (OR 2.09, 95% CI 1.16-3.75, P = 0.01). Consistently, the level of serum transforming growth factor beta1 was also significantly greater in acquired sick sinus syndrome group than in controls (5.3+/-3.4 ng/ml vs. 3.7+/-2.4 ng/ml, P = 0.01). In addition, the CC/CT genotypes showed a higher transforming growth factor-beta1 serum level than the TT genotype (4.25 +/- 2.50 ng/ml vs. 2.71+/- 1.76 ng/ml, P = 0.028) in controls. CONCLUSION: Transforming growth factor-beta1 T869C polymorphism, correlated with high serum transforming growth factor-beta1 levels, is associated with susceptibility to acquired sick sinus syndrome. PMID- 27380175 TI - Association of Thrombocytopenia and Mortality in Critically Ill Patients on Continuous Renal Replacement Therapy. AB - BACKGROUND: Both acute kidney injury (AKI) requiring dialysis and thrombocytopenia are very common and have been independently associated with mortality and morbidity in critically ill patients. Thrombocytopenia is an independent risk factor for AKI and also a marker of disease severity. There is a paucity of literature on the prevalence, incidence, and outcome of thrombocytopenia in patients receiving continuous renal replacement therapy (CRRT). We aimed at identifying the impact of thrombocytopenia on patients in the intensive care unit (ICU) with AKI requiring CRRT. METHODS: We retrospectively studied consecutive adult patients admitted to the ICU from December 9, 2006 through December 31, 2009, with follow-up for 12 months who received CRRT. Thrombocytopenia was defined as platelet counts of <150,000/ul and severe thrombocytopenia as platelet counts of <50,000/ul. Outcomes were mortality and length of stay, both in ICU and hospital. Descriptive summary and multivariable regression model were used for data analyses. RESULTS: Out of the 541 patients studied, thrombocytopenia was observed in 350 (65%) prior to the initiation of CRRT, and 107 (20%) developed it after CRRT was started. The average age of patients was 61 +/- 15; 328 (61%) were men. Sepsis was present in more than half of the patients requiring CRRT. We found a graded increase (p = 0.01) in ICU mortality with worsening platelet counts; 33, 40, and 51% of patients died in ICU with platelet counts >=150,000/MUl, 50,000-149,000/MUl, and <=50,000/ul, respectively. Thrombocytopenia prior to the initiation of CRRT and severe thrombocytopenia prior to and following the initiation of CRRT were associated with increased ICU mortality (p = 0.01). CONCLUSIONS: Thrombocytopenia is very common in ICU patients who are on CRRT, and both thrombocytopenia prior to the start of CRRT and severe thrombocytopenia developing after the initiation of CRRT significantly impact patient survival. Future large-scale prospective studies will help to explore the role of platelet in prognostication of outcome among CRRT patients. PMID- 27380174 TI - Adaptive Epigenetic Differentiation between Upland and Lowland Rice Ecotypes Revealed by Methylation-Sensitive Amplified Polymorphism. AB - The stress-induced epimutations could be inherited over generations and play important roles in plant adaption to stressful environments. Upland rice has been domesticated in water-limited environments for thousands of years and accumulated drought-induced epimutations of DNA methylation, making it epigenetically differentiated from lowland rice. To study the epigenetic differentiation between upland and lowland rice ecotypes on their drought-resistances, the epigenetic variation was investigated in 180 rice landraces under both normal and osmotic conditions via methylation-sensitive amplified polymorphism (MSAP) technique. Great alterations (52.9~54.3% of total individual-locus combinations) of DNA methylation are recorded when rice encountering the osmotic stress. Although the general level of epigenetic differentiation was very low, considerable level of PhiST (0.134~0.187) was detected on the highly divergent epiloci (HDE). The HDE detected in normal condition tended to stay at low levels in upland rice, particularly the ones de-methylated in responses to osmotic stress. Three out of four selected HDE genes differentially expressed between upland and lowland rice under normal or stressed conditions. Moreover, once a gene at HDE was up-/down regulated in responses to the osmotic stress, its expression under the normal condition was higher/lower in upland rice. This result suggested expressions of genes at the HDE in upland rice might be more adaptive to the osmotic stress. The epigenetic divergence and its influence on the gene expression should contribute to the higher drought-resistance in upland rice as it is domesticated in the water-limited environment. PMID- 27380176 TI - An Optimal Bahadur-Efficient Method in Detection of Sparse Signals with Applications to Pathway Analysis in Sequencing Association Studies. AB - Next-generation sequencing data pose a severe curse of dimensionality, complicating traditional "single marker-single trait" analysis. We propose a two stage combined p-value method for pathway analysis. The first stage is at the gene level, where we integrate effects within a gene using the Sequence Kernel Association Test (SKAT). The second stage is at the pathway level, where we perform a correlated Lancaster procedure to detect joint effects from multiple genes within a pathway. We show that the Lancaster procedure is optimal in Bahadur efficiency among all combined p-value methods. The Bahadur efficiency,[Formula: see text], compares sample sizes among different statistical tests when signals become sparse in sequencing data, i.e. epsilon ->0. The optimal Bahadur efficiency ensures that the Lancaster procedure asymptotically requires a minimal sample size to detect sparse signals ([Formula: see text]). The Lancaster procedure can also be applied to meta-analysis. Extensive empirical assessments of exome sequencing data show that the proposed method outperforms Gene Set Enrichment Analysis (GSEA). We applied the competitive Lancaster procedure to meta-analysis data generated by the Global Lipids Genetics Consortium to identify pathways significantly associated with high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and total cholesterol. PMID- 27380177 TI - The Coda of the Transient Response in a Sensitive Cochlea: A Computational Modeling Study. AB - In a sensitive cochlea, the basilar membrane response to transient excitation of any kind-normal acoustic or artificial intracochlear excitation-consists of not only a primary impulse but also a coda of delayed secondary responses with varying amplitudes but similar spectral content around the characteristic frequency of the measurement location. The coda, sometimes referred to as echoes or ringing, has been described as a form of local, short term memory which may influence the ability of the auditory system to detect gaps in an acoustic stimulus such as speech. Depending on the individual cochlea, the temporal gap between the primary impulse and the following coda ranges from once to thrice the group delay of the primary impulse (the group delay of the primary impulse is on the order of a few hundred microseconds). The coda is physiologically vulnerable, disappearing when the cochlea is compromised even slightly. The multicomponent sensitive response is not yet completely understood. We use a physiologically based, mathematical model to investigate (i) the generation of the primary impulse response and the dependence of the group delay on the various stimulation methods, (ii) the effect of spatial perturbations in the properties of mechanically sensitive ion channels on the generation and separation of delayed secondary responses. The model suggests that the presence of the secondary responses depends on the wavenumber content of a perturbation and the activity level of the cochlea. In addition, the model shows that the varying temporal gaps between adjacent coda seen in experiments depend on the individual profiles of perturbations. Implications for non-invasive cochlear diagnosis are also discussed. PMID- 27380178 TI - Reexamining the Efficacy and Value of Percutaneous Coronary Intervention for Patients With Stable Ischemic Heart Disease. AB - Percutaneous coronary intervention (PCI) continues to be performed frequently for patients with stable ischemic heart disease, despite uncertain efficacy. Individual randomized trial data and meta-analyses have not demonstrated that PCI in addition to optimal medical therapy reduces the incidence of death or myocardial infarction in patients with stable disease. The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial did not show benefit for cardiovascular outcomes or mortality but did find a modest improvement in quality of life that did not persist at 3 years. Long-term follow up from COURAGE (up to 15 years) found no differences in mortality, consistent with other published literature. How PCI could reduce long-term mortality or prevent myocardial infarction is not clear because sites of future plaque rupture leading to myocardial infarction are unpredictable and PCI can only treat localized anatomic segments of obstructive atherosclerosis. In addition, PCI is expensive, and the value to society of PCI for stable disease has not been demonstrated. The ISCHEMIA trial will assess the role of PCI for stable ischemic heart disease using newer technology and in patients with greater ischemic burden than in COURAGE. After nearly a decade, the COURAGE trial and other studies have given us pause to critically reexamine the role of PCI for patients with stable ischemic heart disease. Until further research can show that PCI can reduce cardiovascular events in these patients, a first-line strategy of optimal medical therapy is known to be safe, effective, and noninferior to PCI, and our practice should more closely follow this strategy. PMID- 27380179 TI - Perspectives on Safety and Efficacy-The BOLD Phase 2 Extension Study of Siponimod in Relapsing-Remitting Multiple Sclerosis. PMID- 27380181 TI - Expectant management versus multifetal pregnancy reduction in higher order multiple pregnancies containing a monochorionic pair and a review of the literature. AB - PURPOSE: To compare the perinatal outcome in multifetal pregnancies containing a monochorionic twin pair, managed either expectantly or by fetal reduction (MFPR). METHODS: This was a retrospective analysis of prospectively collected data on 47 triplet and 10 quadruplet pregnancies recruited between 10 and 14 weeks. Main outcome measures were miscarriage <24 weeks, preterm birth, fetal growth restriction, birth weight and survival rates. RESULTS: For triplets the miscarriage rates <24 weeks were 6.3 % after reduction and 20.0 % for expectant management and MFPR, respectively. While we recorded no case of severe preterm delivery <30 weeks in the reduction group, it was 25 % in those with expectant management. Mean gestational age and birth weight were significantly higher after fetal reduction than for the conservative approach (37.7 +/- 1.6 weeks vs. 30.9 +/- 3.2 weeks, p < 0.01 and 2676 +/- 705 g vs. 1429 +/- 542 g, p < 0.01). Expectantly managed triplets were complicated by twin-twin transfusion syndrome in 18.8 % and intrauterine fetal death in 8.3 %. Survival rates were 85.4 % for those managed expectantly and 80.0 % after fetal reduction. Mean gestational age of ongoing quadruplets was 26.9 +/- 2.0 weeks vs. 34.5 +/- 4.3 weeks for those with reduction of the monochorionic pair (p < 0.05). Survival rates were 100 % in the reduction group and 58.3 % in the expectant management group (p < 0.05). There was an inverse correlation between the final number of fetuses and the birth weight. CONCLUSION: Fetal reduction in triplets and quadruplets including a monochorionic pair is associated with decreased early prematurity. While in quadruplets the overall survival is higher after reduction, there was no difference for dichorionic triplets with reduction or conservative management. Complications owing to monochorionicity are frequently observed. PMID- 27380180 TI - X-ray absorption spectroscopic characterization of the diferric-peroxo intermediate of human deoxyhypusine hydroxylase in the presence of its substrate eIF5a. AB - Human deoxyhypusine hydroxylase (hDOHH) is an enzyme that is involved in the critical post-translational modification of the eukaryotic translation initiation factor 5A (eIF5A). Following the conversion of a lysine residue on eIF5A to deoxyhypusine (Dhp) by deoxyhypusine synthase, hDOHH hydroxylates Dhp to yield the unusual amino acid residue hypusine (Hpu), a modification that is essential for eIF5A to promote peptide synthesis at the ribosome, among other functions. Purification of hDOHH overexpressed in E. coli affords enzyme that is blue in color, a feature that has been associated with the presence of a peroxo-bridged diiron(III) active site. To gain further insight into the nature of the diiron site and how it may change as hDOHH goes through the catalytic cycle, we have conducted X-ray absorption spectroscopic studies of hDOHH on five samples that represent different species along its reaction pathway. Structural analysis of each species has been carried out, starting with the reduced diferrous state, proceeding through its O2 adduct, and ending with a diferric decay product. Our results show that the Fe?Fe distances found for the five samples fall within a narrow range of 3.4-3.5 A, suggesting that hDOHH has a fairly constrained active site. This pattern differs significantly from what has been associated with canonical dioxygen activating nonheme diiron enzymes, such as soluble methane monooxygenase and Class 1A ribonucleotide reductases, for which the Fe?Fe distance can change by as much as 1 A during the redox cycle. These results suggest that the O2 activation mechanism for hDOHH deviates somewhat from that associated with the canonical nonheme diiron enzymes, opening the door to new mechanistic possibilities for this intriguing family of enzymes. PMID- 27380182 TI - Susceptibility to ambient particulate matter on emergency care utilization for ischemic heart disease in Seoul, Korea. AB - Many epidemiological studies have reported associations between ambient particulate matter (PM) and cardiovascular diseases. However, the effects associated with PM that promote cardiovascular events among susceptible populations who may respond differently than the general population to the same ambient air pollutants remain unclear. We conducted a time-series study with generalized additive models to assess the association between ambient PM10 and emergency department (ED) visits for ischemic heart disease (IHD) in Seoul, Republic of Korea from 2005 to 2009. The ED data and previous medical records within the 5 years of each IHD event to examine the effect of PM10 in a susceptible population were obtained from Health Insurance Review and Assessment Service. Overall, the adjusted relative risks (RRs) of ED visits for IHD were not statistically significant for PM10, but significant positive RRs were found for groups with hypertension (1.018; 95 % confidence interval [CI] 1.002-1.035) and those who are >=80 years of age (1.019; 1.002-1.037) for same-day exposure and with diabetes (1.019; 1.002-1.037) for single-lag models. Subgroup analyses revealed gender differences in ED visits for IHD in hypertensive patients and those who are >=80 years of age; positive correlations were found only in males with the lag models. Our study suggests that ambient PM10 is significantly associated with ED visits for IHD, especially in males with hypertension, diabetes mellitus, or who are aged >=80 years. Identification of populations susceptible to air pollution is of paramount importance to establishing recommendations or guidelines for high-risk individuals. PMID- 27380183 TI - Reviewing the anaerobic digestion and co-digestion process of food waste from the perspectives on biogas production performance and environmental impacts. AB - In this paper, factors that affect biogas production in the anaerobic digestion (AD) and anaerobic co-digestion (coAD) processes of food waste are reviewed with the aim to improve biogas production performance. These factors include the composition of substrates in food waste coAD as well as pre-treatment methods and anaerobic reactor system designs in both food waste AD and coAD. Due to the characteristics of the substrates used, the biogas production performance varies as different effects are exhibited on nutrient balance, inhibitory substance dilution, and trace metal element supplement. Various types of pre-treatment methods such as mechanical, chemical, thermal, and biological methods are discussed to improve the rate-limiting hydrolytic step in the digestion processes. The operation parameters of a reactor system are also reviewed with consideration of the characteristics of the substrates. Since the environmental awareness and concerns for waste management systems have been increasing, this paper also addresses possible environmental impacts of AD and coAD in food waste treatment and recommends feasible methods to reduce the impacts. In addition, uncertainties in the life cycle assessment (LCA) studies are also discussed. PMID- 27380184 TI - Phosphorus characteristics, distribution, and relationship with environmental factors in surface sediments of river systems in Eastern China. AB - Phosphorus (P) is an essential nutrient for aquatic organisms. However, too much P discharged into limnetic ecosystems can induce eutrophication. The concentration of P in freshwater ecosystems has escalated in Eastern China due to overuse of fertilizer and excess emission of sewage, which is the result of the development of industry and agriculture in this area. However, little is known about the P characteristics and its environmental factors in river systems. Here, we present the results of P characterization and its relationships with environmental factors in Eastern China by applying SMT and (31)P-NMR methods. The results showed that the concentrations of P in surface sediments varied with the river system, and more than 50 % of the samples had P concentrations exceeding 500 mg kg(-1). HCl-Pi was the dominant Pi in surface sediments, with the highest percentage (96.5 %) in the Yellow River System. Mono-P was the dominant Po in river sediments, followed by DNA-P. The PCA approach indicated that NaOH-Pi and ortho-P clustered in one group, with a second group including mono-P, diesters-P, and HCl-Pi. Phon-P and pyro-P belonged to different groups. On a regional scale, NaOH-Pi and Po showed a negative relationship with pH in sediments. Continuous eutrophication was induced by the presence of dams, and oxygen-consuming pollutants, such as NH3-N and CODcr, even when external P input was cut in heavily polluted rivers. The research revealed the characteristics of P in different river systems and proposed a conceptual model of P biogeochemical cycles in heavily polluted rivers. Results from this study may provide insight into P characteristics in Eastern China and would set a scientific basis for effective P management in developing countries. PMID- 27380185 TI - Correlation of transverse relaxation time with structure of biological tissue. AB - Transverse spin-spin relaxation of liquids entrapped in nanocavities with different orientational order is theoretically investigated. Based on the bivariate normal distribution of nanocavities directions, we have calculated the anisotropy of the transverse relaxation time for biological systems, such as collagenous tissues, articular cartilage, and tendon. In the framework of the considered model, the dipole-dipole interaction is determined by a single coupling constant. The calculation results for the transverse relaxation time explain the angular dependence observed in MRI experiments with biological objects. The good agreement with the experimental data is obtained by adjustment of only one parameter which characterizes the disorder in fiber orientations. The relaxation time is correlated with the degree of ordering in biological tissues. Thus, microstructure of the tissues can be revealed from the measurement of relaxation time anisotropy. The clinical significance of the correlation, especially in the detection of damage must be evaluated in a large prospective clinical trials. PMID- 27380186 TI - Two SNAP-25 genetic variants in the binding site of multiple microRNAs and susceptibility of ADHD: A meta-analysis. AB - The aim of this meta-analysis is to assess the associations between two most widely investigated polymorphisms (rs3746544 and rs1051312) in the 3'UTR of the SNAP-25 gene and susceptibility of ADHD. Two investigators selected related studies and assessed methodological quality independently. Six studies were included in this meta-analysis for a total of 715 cases and 655 controls. There is no apparent association between rs3746544 polymorphisms and risk of ADHD. However, subgroup analysis based on ethnicity demonstrated a strong association between rs3746544 polymorphism and ADHD in the subset of Asian participants, but not among Caucasians. Compared to the T allele, the allele G was associated with a significantly decreased risk of developing ADHD in the Asian population (odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.52-0.95, p = 0.02). The association between the TT genotype and ADHD risk was also significantly increased as compared to G/T (OR = 1.56, 95% CI = 1.00-2.44, p = 0.05) and the dominant genetic model (GG + GT vs. TT: OR = 1.51, 95% CI = 1.07-2.13, p = 0.02). For the rs1051312 SNP, being homozygous for the minor allele (C/C) was associated with a 3.66 higher odds of ADHD as compared to cases homozygous for the major allele (T/T) (95% CI = 1.64-8.13, p = 0.001), and 3.57 higher odds as compared to heterozygous (C/T) carriers (95% CI = 2.01-12.90, p < 0.001). Our results suggest that the polymorphisms rs3746544 and rs1051312 may increase the odds of developing ADHD. Additional studies are needed to confirm these findings. PMID- 27380187 TI - Distributed Cognition and Distributed Morality: Agency, Artifacts and Systems. AB - There are various philosophical approaches and theories describing the intimate relation people have to artifacts. In this paper, I explore the relation between two such theories, namely distributed cognition and distributed morality theory. I point out a number of similarities and differences in these views regarding the ontological status they attribute to artifacts and the larger systems they are part of. Having evaluated and compared these views, I continue by focussing on the way cognitive artifacts are used in moral practice. I specifically conceptualise how such artifacts (a) scaffold and extend moral reasoning and decision-making processes, (b) have a certain moral status which is contingent on their cognitive status, and (c) whether responsibility can be attributed to distributed systems. This paper is primarily written for those interested in the intersection of cognitive and moral theory as it relates to artifacts, but also for those independently interested in philosophical debates in extended and distributed cognition and ethics of (cognitive) technology. PMID- 27380188 TI - Comparative Study of Poly (epsilon-Caprolactone) and Poly(Lactic-co-Glycolic Acid) -Based Nanofiber Scaffolds for pH-Sensing. AB - PURPOSE: This study aims to develop biodegradable and biocompatible polymer-based nanofibers that continuously monitor pH within microenvironments of cultured cells in real-time. In the future, these fibers will provide a scaffold for tissue growth while simultaneously monitoring the extracellular environment. METHODS: Sensors to monitor pH were created by directly electrospinning the sensor components within a polymeric matrix. Specifically, the entire fiber structure is composed of the optical equivalent of an electrode, a pH-sensitive fluorophore, an ionic additive, a plasticizer, and a polymer to impart mechanical stability. The resulting poly(epsilon-caprolactone) (PCL) and poly(lactic-co glycolic acid) (PLGA) based sensors were characterized by morphology, dynamic range, reversibility and stability. Since PCL-based nanofibers delivered the most desirable analytical response, this matrix was used for cellular studies. RESULTS: Electrospun nanofiber scaffolds (NFSs) were created directly out of optode material. The resulting NFS sensors respond to pH changes with a dynamic range centered at 7.8 +/- 0.1 and 9.6 +/- 0.2, for PCL and PLGA respectively. NFSs exhibited multiple cycles of reversibility with a lifetime of at least 15 days with preservation of response characteristics. By comparing the two NFSs, we found PCL-NFSs are more suitable for pH sensing due to their dynamic range and superior reversibility. CONCLUSION: The proposed sensing platform successfully exhibits a response to pH and compatibility with cultured cells. NSFs will be a useful tool for creating 3D cellular scaffolds that can monitor the cellular environment with applications in fields such as drug discovery and tissue engineering. PMID- 27380189 TI - Quantifying Nanoparticle Internalization Using a High Throughput Internalization Assay. AB - PURPOSE: The internalization of nanoparticles into cells is critical for effective nanoparticle mediated drug delivery. To investigate the kinetics and mechanism of internalization of nanoparticles into cells we have developed a DNA molecular sensor, termed the Specific Hybridization Internalization Probe - SHIP. METHODS: Self-assembling polymeric 'pHlexi' nanoparticles were functionalized with a Fluorescent Internalization Probe (FIP) and the interactions with two different cell lines (3T3 and CEM cells) were studied. The kinetics of internalization were quantified and chemical inhibitors that inhibited energy dependent endocytosis (sodium azide), dynamin dependent endocytosis (Dyngo-4a) and macropinocytosis (5-(N-ethyl-N-isopropyl) amiloride (EIPA)) were used to study the mechanism of internalization. RESULTS: Nanoparticle internalization kinetics were significantly faster in 3T3 cells than CEM cells. We have shown that ~90% of the nanoparticles associated with 3T3 cells were internalized, compared to only 20% of the nanoparticles associated with CEM cells. Nanoparticle uptake was via a dynamin-dependent pathway, and the nanoparticles were trafficked to lysosomal compartments once internalized. CONCLUSION: SHIP is able to distinguish between nanoparticles that are associated on the outer cell membrane from nanoparticles that are internalized. This study demonstrates the assay can be used to probe the kinetics of nanoparticle internalization and the mechanisms by which the nanoparticles are taken up by cells. This information is fundamental for engineering more effective nanoparticle delivery systems. The SHIP assay is a simple and a high-throughput technique that could have wide application in therapeutic delivery research. PMID- 27380190 TI - Population Pharmacokinetic Modelling of Morphine, Gabapentin and their Combination in the Rat. AB - PURPOSE: The combination of morphine and gabapentin seems promising for the treatment of postoperative and neuropathic pain. Despite the well characterised pharmacodynamic interaction, little is known about possible pharmacokinetic interactions. The aim of this study was to evaluate whether co-administration of the two drugs leads to modifications of their pharmacokinetic profiles. METHODS: The pharmacokinetics of morphine, morphine-3-glucuronide and gabapentin were characterised in rats following subcutaneous injections of morphine, gabapentin or their combination. Non-linear mixed effects modelling was applied to describe the pharmacokinetics of the compounds and possible interactions. RESULTS: The plasma-concentration-time profiles of morphine and gabapentin were best described using a three- and a one-compartment disposition model respectively. Dose dependencies were found for morphine absorption rate and gabapentin bioavailability. Enterohepatic circulation of morphine-3-glucuronide was modelled using an oscillatory model. The combination did not lead to pharmacokinetic interactions for morphine or gabapentin but resulted in an estimated ~33% diminished morphine-3-glucuronide formation. CONCLUSIONS: The finding of a lack of pharmacokinetic interaction strengthens the notion that the combination of the two drugs leads to better efficacy in pain treatment due to interaction at the pharmacodynamic level. The interaction found between gabapentin and morphine-3 glucuronide, the latter being inactive, might not have any clinical relevance. PMID- 27380192 TI - Microstructure of Tablet-Pharmaceutical Significance, Assessment, and Engineering. AB - PURPOSE: To summarize the microstructure - property relationship of pharmaceutical tablets and approaches to improve tablet properties through tablet microstructure engineering. METHOD: The main topics reviewed here include: 1) influence of material properties and manufacturing process parameters on the evolution of tablet microstructure; 2) impact of tablet structure on tablet properties; 3) assessment of tablet microstructure; 4) development and engineering of tablet microstructure. RESULTS: Microstructure plays a decisive role on important pharmaceutical properties of a tablet, such as disintegration, drug release, and mechanical strength. Useful information on mechanical properties of a powder can be obtained from analyzing tablet porosity-pressure data. When helium pycnometry fails to accurately measure true density of a water containing powder, non-linear regression of tablet density-pressure data is a useful alternative method. A component that is more uniformly distributed in a tablet generally exerts more influence on the overall tablet properties. CONCLUSION: During formulation development, it is highly recommended to examine the relationship between any property of interest and tablet porosity when possible. Tablet microstructure can be engineered by judicious selection of formulation composition, including the use of the optimum solid form of the drug and appropriate type and amount of excipients, and controlling manufacturing process. PMID- 27380193 TI - Diagnostic problems in acquired bone marrow failure syndromes. PMID- 27380191 TI - Is There an Optimal Formulation and Delivery Strategy for Subunit Vaccines? AB - Modern vaccine design has moved away from attenuated or inactivated whole pathogen vaccines to more pure and defined subunit vaccines. However subunit antigens have poor bioavailability and stability and lack immunogenicity. To overcome these issues subunit vaccines have to be administered in a suitable delivery system in combination with immune stimulants. Many different delivery systems have been developed and investigated each having different modes of action, for example increasing delivery and/or sustaining delivery of antigen to immune cells. In addition a number of different routes of immunization are possible and these can play a crucial role in determining the fate of an immune response. In this review the different strategies for the delivery of prophylactic and therapeutic subunit vaccines along with the impact of these on the immune responses generated are discussed. PMID- 27380194 TI - Iron-induced epigenetic abnormalities of mouse bone marrow through aberrant activation of aconitase and isocitrate dehydrogenase. AB - Iron overload remains a concern in myelodysplastic syndrome (MDS) patients. Iron chelation therapy (ICT) thus plays an integral role in the management of these patients. Moreover, ICT has been shown to prolong leukemia-free survival in MDS patients; however, the mechanisms responsible for this effect are unclear. Iron is a key molecule for regulating cytosolic aconitase 1 (ACO1). Additionally, the mutation of isocitrate dehydrogenase (IDH), the enzyme downstream of ACO1 in the TCA cycle, is associated with epigenetic abnormalities secondary to 2 hydroxyglutarate (2-HG) and DNA methylation. However, epigenetic abnormalities observed in many MDS patients occur without IDH mutation. We hypothesized that iron itself activates the ACO1-IDH pathway, which may increase 2-HG and DNA methylation, and eventually contribute to leukemogenesis without IDH mutation. Using whole RNA sequencing of bone marrow cells in iron-overloaded mice, we observed that the enzymes, phosphoglucomutase 1, glycogen debranching enzyme, and isocitrate dehydrogenase 1 (Idh1), which are involved in glycogen and glucose metabolism, were increased. Digital PCR further showed that Idh1 and Aco1, enzymes involved in the TCA cycle, were also elevated. Additionally, enzymatic activities of TCA cycle and methylated DNA were increased. Iron chelation reversed these phenomena. In conclusion, iron activation of glucose metabolism causes an increase of 2-HG and DNA methylation. PMID- 27380196 TI - [Not Available]. PMID- 27380195 TI - Software-based PET-MR image coregistration: combined PET-MRI for the rest of us! AB - BACKGROUND: With the introduction of hybrid positron emission tomography/magnetic resonance imaging (PET/MRI), a new imaging option to acquire multimodality images with complementary anatomical and functional information has become available. Compared with hybrid PET/computed tomography (CT), hybrid PET/MRI is capable of providing superior anatomical detail while removing the radiation exposure associated with CT. The early adoption of hybrid PET/MRI, however, has been limited. OBJECTIVE: To provide a viable alternative to the hybrid PET/MRI hardware by validating a software-based solution for PET-MR image coregistration. MATERIALS AND METHODS: A fully automated, graphics processing unit-accelerated 3 D deformable image registration technique was used to align PET (acquired as PET/CT) and MR image pairs of 17 patients (age range: 10 months-21 years, mean: 10 years) who underwent PET/CT and body MRI (chest, abdomen or pelvis), which were performed within a 28-day (mean: 10.5 days) interval. MRI data for most of these cases included single-station post-contrast axial T1-weighted images. Following registration, maximum standardized uptake value (SUVmax) values observed in coregistered PET (cPET) and the original PET were compared for 82 volumes of interest. In addition, we calculated the target registration error as a measure of the quality of image coregistration, and evaluated the algorithm's performance in the context of interexpert variability. RESULTS: The coregistration execution time averaged 97+/-45 s. The overall relative SUVmax difference was 7% between cPET-MRI and PET/CT. The average target registration error was 10.7+/-6.6 mm, which compared favorably with the typical voxel size (diagonal distance) of 8.0 mm (typical resolution: 0.66 mm * 0.66 mm * 8 mm) for MRI and 6.1 mm (typical resolution: 3.65 mm * 3.65 mm * 3.27 mm) for PET. The variability in landmark identification did not show statistically significant differences between the algorithm and a typical expert. CONCLUSION: We have presented a software-based solution that achieves the many benefits of hybrid PET/MRI scanners without actually needing one. The method proved to be accurate and potentially clinically useful. PMID- 27380197 TI - Investigation of K X-ray intensity ratios of some 4d transition metals depending on the temperature. AB - In this paper, we have studied the intensity ratios Kbeta/Kalpha depending on the temperature for transition elements Mo, Nb, Zr and Y by 59.5keV gamma-rays from a 100 mCi (241)Am radioisotope point source. The Kalpha and Kbeta emission spectra of Mo, Nb, Zr and Y were measured by using a Si (Li) solid-state detector at temperature between 40 and 400 degrees C. sigmaKalpha and sigmaKbeta production cross-sections, Kbeta/Kalpha intensity ratios, asymmetry factor, energy shifts and full width half maximum (FWHM) values of the elements have been calculated. Temperature-dependent changes of the parameters are tabulated and given in the graphical forms. Based on the results obtained, Kbeta/Kalpha X-ray intensity ratios of the elements are dependent on the temperature. It is shown that sigmaKbeta fluorescence cross sections of Mo, Nb and Zr have more increase rate than sigmaKalpha fluorescence cross sections with increasing temperature. For Y, sigmaKalpha and sigmaKbeta production cross-sections firstly decrease, then increase. In general, Kbeta/Kalpha X-ray intensity ratios tend to increase with increasing temperature. Some significant shifts are observed in Kalpha and Kbeta emission spectra of Mo and Y. These results may contribute to the XRF studies of transition metals. PMID- 27380198 TI - [Not Available]. PMID- 27380199 TI - [Not Available]. PMID- 27380201 TI - Local Protein Structure Refinement via Molecular Dynamics Simulations with locPREFMD. AB - A method for the local refinement of protein structures that targets improvements in local stereochemistry while preserving the overall fold is presented. The method uses force field-based minimization and sampling via molecular dynamics simulations with a modified force field to bring bonds, angles, and torsion angles into an acceptable range for high-resolution protein structures. The method is implemented in the locPREFMD web server and was tested on computational models submitted to CASP11. Using MolProbity scores as the main assessment criterion, the locPREFMD method significantly improves the stereochemical quality of given input models close to the quality expected for experimental structures while maintaining the Calpha coordinates of the initial model. PMID- 27380200 TI - A Novel Technique of Synthesis of Highly Fluorescent Carbon Nanoparticles from Broth Constituent and In-vivo Bioimaging of C. elegans. AB - Here we have demonstrated a novel single step technique of synthesis of highly fluorescent carbon nanoparticles (CNPs) from broth constituent and in vivo bioimaging of Caenorhabditis elegans (C. elegans) with the synthesized CNPs has been presented. The synthesized CNPs has been characterized by the UV-visible (UV Vis) absorption spectroscopy, transmission electron microscopy (TEM) and Raman studies. The sp (2) cluster size of the synthesized samples has been determined from the measured Raman spectra by fitting it with the theoretical skew Lorentzian (Breit-Wigner- Fano (BWF)) line shape. The synthesised materials are showing excitation wavelength dependent tunable photoluminescence (PL) emission characteristics with a high quantum yield (QY) of 3 % at a very low concentration of CNPs. A remarkable increase in the intensity of PL emission from 16 % to 39 % in C. elegans has also been observed when the feeding concentration of CNPs to C. elegans is increased from 0.025 % to 0.1 % (w/v). The non-toxicity and water solubility of the synthesized material makes it ideal candidate for bioimaging. PMID- 27380202 TI - Effects of thigh holster use on kinematics and kinetics of active duty police officers. AB - BACKGROUND: Body armour, duty belts and belt mounted holsters are standard equipment used by the Swedish police and have been shown to affect performance of police specific tasks, to decrease mobility and to potentially influence back pain. This study aimed to investigate the effects on gait kinematics and kinetics associated with use of an alternate load carriage system incorporating a thigh holster. METHODS: Kinematic, kinetic and temporospatial data were collected using three dimensional gait analysis. Walking tests were conducted with nineteen active duty police officers under three different load carriage conditions: a) body armour and duty belt, b) load bearing vest, body armour and thigh holster and c) no equipment (control). FINDINGS: No significant differences between testing conditions were found for temporospatial parameters. Range of trunk rotation was reduced for both load carriage conditions compared to the control condition (p<0.017). Range of hip rotation was more similar to the control condition when wearing thigh holster rather than the belt mounted hip holster (p<0.017). Moments and powers for both left and right ankles were significantly greater for both of the load carriage conditions compared to the control condition (p<0.017). INTERPRETATION: This study confirms that occupational loads carried by police have a significant effect on gait kinematics and kinetics. Although small differences were observed between the two load carriage conditions investigated in this study, results do not overwhelmingly support selection of one design over the other. PMID- 27380203 TI - Searching for strategies to reduce the mechanical demands of the sit-to-stand task with a muscle-actuated optimal control model. AB - BACKGROUND: The sit-to-stand task, which involves rising unassisted from sitting on a chair to standing, is important in daily life. Many people with muscle weakness, reduced range of motion or loading-related pain in a particular joint have difficulty performing the task. How should a person suffering from such impairment best perform the sit-to-stand task and, in the case of pain in a particular joint, with reduced loading of that joint? METHODS: We developed a musculoskeletal model with reference parameter values based on properties of healthy strong subjects. The model's muscle stimulation-time input was optimized using direct collocation to find strategies that yielded successful sit-to-stand task performance with minimum 'control effort' for the reference set and modified sets of parameter values, and with constraints on tibiofemoral compression force. FINDINGS: The sit-to-stand task could be performed successfully and realistically by the reference model, by a model with isometric knee extensor forces reduced to 40% of reference, by a model with isometric forces of all muscles reduced to 45% of reference, and by the reference model with the tibiofemoral compression force constrained during optimization to 65% of the peak value in the reference condition. INTERPRETATION: The strategies found by the model in conditions other than reference could be interpreted well on the basis of cost function and task biomechanics. The question remains whether it is feasible to teach patients with musculoskeletal impairments or joint pain to perform the sit-to-stand task according to strategies that are optimal according to the simulation model. PMID- 27380204 TI - Complexity, fractal dynamics and determinism in treadmill ambulation: Implications for clinical biomechanists. AB - BACKGROUND: Reduced inter-stride complexity during ambulation may represent a pathologic state. Evidence is emerging that treadmill training for rehabilitative purposes may constrain the locomotor system and alter gait dynamics in a way that mimics pathological states. The purpose of this study was to examine the dynamical system components of gait complexity, fractal dynamics and determinism during treadmill ambulation. METHODS: Twenty healthy participants aged 23.8 (1.2) years walked at preferred walking speeds for 6min on a motorized treadmill and overground while wearing APDM 6 Opal inertial monitors. Stride times, stride lengths and peak sagittal plane trunk velocities were measured. Mean values and estimates of complexity, fractal dynamics and determinism were calculated for each parameter. Data were compared between overground and treadmill walking conditions. FINDINGS: Mean values for each gait parameter were statistically equivalent between overground and treadmill ambulation (P>0.05). Through nonlinear analyses, however, we found that complexity in stride time signals (P<0.001), and long-range correlations in stride time and stride length signals (P=0.005 and P=0.024, respectively), were reduced on the treadmill. INTERPRETATION: Treadmill ambulation induces more predictable inter-stride time dynamics and constrains fluctuations in stride times and stride lengths, which may alter feedback from destabilizing perturbations normally experienced by the locomotor control system during overground ambulation. Treadmill ambulation, therefore, may provide less opportunity for experiencing the adaptability necessary to successfully ambulate overground. Investigators and clinicians should be aware that treadmill ambulation will alter dynamic gait characteristics. PMID- 27380205 TI - Antimalarial and cytotoxic quassinoids from the roots of Brucea javanica. AB - Two new quassinoids, brujavanol A (1) and brujavanol B (2), along with five known quassinoids (3-7), were isolated from the roots of Brucea javanica. Their structures were elucidated by spectroscopic methods. The antimalarial and cytotoxic activities of the isolated compounds were also assessed. Compounds 1 and 2 exhibited significant in vitro cytotoxicity against human oral cavity cancer (KB) cells with IC50 values of 1.30 and 2.36 MUg/ml, respectively, whereas compound 3 showed excellent antiplasmodial activity against the Plasmodium falciparum strains, K1 (IC50 = 0.58 MUg/ml). PMID- 27380206 TI - Validating Evidence and Using Standard Outcomes for Recurrent Pregnancy Loss Tests and Treatments. AB - Unproven diagnostic tests and treatments for recurrent pregnancy loss patients can no longer be justified. The use of accepted study guidelines for conducting randomized trials, observational studies, systematic reviews and meta-analyses, diagnostic tests, animal research, and the development of standardized consensus derived outcomes would greatly improve the quality of recurrent pregnancy loss studies and their reporting. PMID- 27380207 TI - Immunologic Abnormalities, Treatments, and Recurrent Pregnancy Loss: What Is Real and What Is Not? AB - Recurrent pregnancy loss, depending on the definition, affects 1% to 3% of women aiming to have a child. Little is known about the direct causes of recurrent pregnancy loss, and the condition is considered to have a multifactorial and complex pathogenesis. The aim of this review was to summarize the evaluation and the management of the condition with specific emphasis on immunologic biomarkers identified as risk factors as well as current immunologic treatment options. The review also highlights and discusses areas in need of further research. PMID- 27380208 TI - Early, rapidly progressive enteral nutrition promotes growth of very low birth weight (VLBW) infants. AB - AIM: This study describes the effects of a quality improvement program to promote improved postnatal nutrition on the growth of very low birth weight (VLBW) infants. METHODS: Daily data regarding nutrition and growth were collected from the medical record of VLBW infants born during 1995-2010. The infants were grouped by year of birth in order to compare infants from before, during and after the policy change. Evaluation of growth included age in days at a return to birth weight and the proportion of infants with weight below the 10th percentile at discharge. RESULTS: The caloric and protein intake improved significantly. The age at a return to birth weight fell (p < 0.01) from 14.6 +/- 5 d to 11 +/- 8 d after the change. The proportion of infants with a discharge weight below the 10th percentile for corrected age fell (p < 0.01) from 72.1% to 42.1%. Data on enteral feeding showed that increased rate of enteral feeds (EF) was associated with better growth (p < 0.001). CONCLUSION: Increasing awareness led to increase in caloric and protein intake in VLBW infants. Aggressive EF was associated with more rapid weight gain. However, the provision of protein and calories during the first 2 weeks of life still falls short of the latest European Society of Pediatric Gastroenterology, Hepatology and Nutrition recommendations. PMID- 27380209 TI - Ligation-free technique for dorsal vascular complex control during laparoscopic radical prostatectomy: a single-center experience from China. AB - OBJECTIVE: To illustrate a ligation-free technique and compare perioperative and postoperative outcomes of this technique versus the standard suture method. PATIENTS AND METHODS: This study is a retrospective review of 233 consecutive patients with localized prostate cancer who underwent ligation-free technique (n = 180, Group 1) or standard ligation (n = 53, Group 2) at an academic institution from February 2010 to January 2014. RESULTS AND LIMITATIONS: Operative time was significantly shorter in Group 1 than in Group 2 (148.47 vs. 164.25 min, p = 0.000). No difference in EBL was noted between the groups (191.11 vs. 185.06 mL, p = 0.055). Postoperative continence rates at 3, 6, and 12 months in Groups 1 and 2 were 40.0 versus 24.5, 54.4 versus 37.7, and 73.9 versus 71.7 %, respectively. These differences were statistically significant. No patient in either group had a positive apical surgical margin. During follow-up, tumor recurrence or metastasis was not observed in any patient. Limitations of the study include this retrospective study of a single-center experience and lack of potency appraisal. CONCLUSIONS: This present ligation-free technique showed a statistically significant shorter interval to recovery of continence and higher continence rates in short-term postoperative results by contrast to conventional suture ligation, but no significant difference was revealed in long-term urinary control. We offer this technique and the correlative data to provide more information for deeply understanding the precise construction of the dorsal vascular complex and the mechanism of urinary control. PMID- 27380210 TI - Analysis of the Association of Clubhouse Membership with Overall Costs of Care for Mental Health Treatment. AB - We examined whether frequency of attendance at the B'More Clubhouse was associated with lower mental health care costs in the Medicaid database, and whether members in the B'More Clubhouse (n = 30) would have lower mental health care costs compared with a set of matched controls from the same claims database (n = 150). Participants who attended the Clubhouse 3 days or more per week had mean 1-year mental health care costs of US $5697, compared to $14,765 for those who attended less often. B'More Clubhouse members had significantly lower annual total mental health care costs than the matched comparison group ($10,391 vs. $15,511; p < 0.0001). Membership in the B'More Clubhouse is associated with a substantial beneficial influence on health care costs. PMID- 27380211 TI - Robot-assisted gastrectomy for cancer. AB - BACKGROUND: Laparoscopic gastrectomy for cancer is commonly considered a challenging procedure. The technical drawbacks of laparoscopy have been addressed by robotic technology, which can facilitate demanding reconstructions and fine dissection. These features confer potential advantages in the execution of lymphadenectomy. OBJECTIVES: Here, we illustrate our technique of robotic gastrectomy and discuss advantages and drawbacks by reviewing the current literature. MATERIALS AND METHODS: We describe our technique for robot-assisted distal and total gastrectomy for cancer and assess the current literature dealing with short-term outcomes, immediate oncologic measures, and long-term oncologic outcomes of robot-assisted gastrectomy, in comparison with conventional laparoscopic and open surgery. RESULTS: The robotic procedure seems to be as safe and effective as conventional gastrectomy for gastric cancer, with a longer operative time and decreased blood loss in comparison with laparoscopic gastrectomy. CONCLUSION: The technical advantages offered by robotics could help to standardize minimally invasive D2 lymphadenectomy and enable surgeons to perform this procedure routinely. Despite the scarcity of long-term data on survival, immediate oncological measures (lymph node yield and margin status) are encouraging. Further studies investigating the long-term oncological outcomes are required. PMID- 27380213 TI - [Not Available]. PMID- 27380214 TI - Does Nocturnal Hypotension Play a Causal Role in Nonarteritic Anterior Ischemic Optic Neuropathy? PMID- 27380215 TI - JAMA Internal Medicine-The Year in Review, 2015. PMID- 27380212 TI - Celecoxib and octreotide synergistically ameliorate portal hypertension via inhibition of angiogenesis in cirrhotic rats. AB - Abnormal angiogenesis is critical for portal hypertension in cirrhosis. Except for etiological treatment, no efficient medication or regime has been explored to treat the early stage of cirrhosis when angiogenesis is initiated or overwhelming. In this study, we explored an anti-angiogenesis effort through non cytotoxic drugs octreotide and celecoxib to treat early stage of cirrhotic portal hypertension in an animal model. Peritoneal injection of thioacetamide (TAA) was employed to induce liver cirrhosis in rats. A combination treatment of celecoxib and octreotide was found to relieve liver fibrosis, portal venous pressure, micro hepatic arterioportal fistulas, intrahepatic and splanchnic angiogenesis. Celecoxib and octreotide exerted their anti-angiogenesis effect via an axis of cyclooxygenase-2/prostaglandin E2/EP-2/somatostatin receptor-2, which consequently down-regulated phosphorylation of extracellular signal-regulated kinase (p-ERK)-hypoxia-inducible factor-1alpha (HIF-1alpha)-vascular endothelial growth factor (VEGF) integrated signaling pathways. In conclusions, combination of celecoxib and octreotide synergistically ameliorated liver fibrosis and portal hypertension of the cirrhotic rats induced by TAA via the inhibition of intrahepatic and extrahepatic angiogenesis. The potential mechanisms behind the regimen may due to the inactivation of p-ERK-HIF-1alpha-VEGF signaling pathway. PMID- 27380216 TI - An overview of wetlands of Saudi Arabia: Values, threats, and perspectives. AB - The wetlands of Saudi Arabia are located in a water-stressed region that is highly vulnerable to climate and other global changes. Sebkhas, mudflats, mangroves, and wadis are the dominant wetlands in the arid regions of North Africa and the Arabian Peninsula. These unique wetlands are recognized as a sanctuary for biodiversity and for their economic services generated from mineral extraction, agriculture, and grazing. Despite their ecological values and societal services, the long-term permanence of Saudi Arabia's wetlands faces strong challenges resulting from human activities associated with sustained population growth, habitat degradation, and coastal development. This paper consolidates a literature review of Saudi Arabia's wetlands from local to global importance, highlights their biodiversity, and identifies threats and evolution of these vulnerable ecosystems in the arid Arabian Peninsula by focusing on the status of key freshwater taxa (Odonata, freshwater fishes, amphibians, and waterbirds) and documenting changes affecting important wetlands. PMID- 27380217 TI - Molecular dynamics-based identification of novel natural mortalin-p53 abrogators as anticancer agents. AB - INTRODUCTION: Cancer is one of the leading causes of mortality worldwide that requires attention in terms of extensive study and research. Eradication of mortalin-p53 interaction that leads to the inhibition of transcriptional activation or blocking of p53 from functioning as a suppressor and induction of nuclear translocation of p53 can prove to be one of the useful approaches for cancer management. RESULTS: In this study, we used structure-based approach to target the p53-binding domain of mortalin in order to prevent mortalin-p53 complex formation. We screened compounds from ZINC database against the modeled mortalin protein using Glide virtual screening. The top two compounds, DTOM (ZINC 28639308) and TTOM (ZINC 38143676) with Glide score of -12.27 and -12.16, respectively, were identified with the potential to abrogate mortalin-p53 interaction. Finally, molecular dynamics simulations were used to analyze the dynamic stability of the ligand-bound complex and it was observed that residues Tyr196, Asn198, Val264 and Thr267 were involved in intermolecular interactions in both the simulated ligand-bound complexes, and thus, these residues may have a paramount role in stabilizing the binding of the ligands with the protein. CONCLUSION: These detailed insights can further facilitate the development of potent inhibitors against mortalin-p53 complex. PMID- 27380218 TI - Cetuximab as treatment for head and neck cancer patients with a previous liver transplant: report of two cases. AB - Cetuximab is a monoclonal antibody against epidermal growth factor receptor useful in the treatment of patients with Head and Neck Squamous Cell Carcinoma combined with radiotherapy or chemotherapy. Its pharmacokinetics are not influenced by hepatic status and there are no specific warnings concerning its indication in patients with impaired hepatic function. Patients with a previous liver transplant are at risk for hepatic toxicity and use immunosupressants to avoid rejection that can interact with other drugs. We present two cases of patients with a previous liver transplant in which cetuximab was administered to treat head and neck cancer. PMID- 27380219 TI - Prevention and management of osteonecrosis of the jaw secondary to bone-targeted therapy in patients with kidney cancer. AB - PURPOSE OF REVIEW: The aim of this revision is prevention and management of osteonecrosis of the jaw (ONJ) secondary to bone-targeted therapy in patients with kidney cancer. RECENT FINDINGS: Patients with kidney cancer treated with zoledronate suffered from ONJ earlier compared with patients with breast cancer or multiple myeloma; among men, ONJ occurred at 24 months of zoledronic acid treatment in more than 80% of the patients and much earlier, in respect to patients with prostate cancer or multiple myeloma. Protective factors against an ONJ can be sequential prescription of different bisphosphonates and female sex. Less data are available on ONJ secondary to denosumab administration in patients with kidney cancer. SUMMARY: Bone metastases, developing in about 30% of the patients with metastatic renal cell carcinoma, are typically osteolytic on imaging and cause significant morbidity and poor quality of life. Incidence of skeletal-related events has been reported to reach 3.38 per year in such patients. To decrease the incidence of ONJ, a maxillofacial examination must be performed in all patients before treatment with bisphosphonates, in particular in patients with metastatic renal cell carcinoma treated with sunitinib alone or in association with zoledronate. The management of ONJ consider a conservative approach. PMID- 27380220 TI - A systematic literature review on the ethics of palliative sedation: an update (2016). AB - PURPOSE OF REVIEW: Palliative sedation has been the subject of intensive debate since its first appearance in 1990. In a 2010 review of palliative sedation, the following areas were identified as lacking in consensus: inconsistent terminology, its use in nonphysical suffering, the ongoing experience of distress, and concern that the practice of palliative sedation may hasten death. This review looks at the literature over the past 6 years and provides an update on these outstanding concerns. RECENT FINDINGS: Good clinical guidelines and policies are still required to address issues of emotional distress and waylay concerns that palliative sedation hastens death. SUMMARY: The empirical evidence suggests some movement toward consensus on the practice of palliative sedation. However, a continued need exists for evidence-informed practice guidelines, education, and research to support the ethical practice of palliative sedation at the end of life. Until that time, clinicians are advised to adopt a framework or guideline that has been expert driven to ensure consistent and ethical use of palliative sedation at the end of life. PMID- 27380221 TI - Service delivery of complex interventions for refractory breathlessness. AB - PURPOSE OF REVIEW: The review considers the evidence for different service models existing for helping people manage the chronic, irreversible breathlessness that accompanies advanced disease. RECENT FINDINGS: Many of the service models that are delivering care have not yet published their results in the scientific literature because these ideas, and the methods to evaluate them, are relatively new. There are three randomized controlled trials published which demonstrate the effectiveness of this approach and one which suggests that more episodes of some intervention components are not necessarily better. SUMMARY: Breathlessness severity gives a better guide to a patient's prognosis than physiological measures in many diseases and the general population. Randomized controlled trial evidence confirms that a complex intervention for breathlessness can improve quality of life, reduce symptom impact, and support carers. Some preliminary data suggest prognosis improvement in some people. Integrated care is needed for both rapidly progressive disease, where death is inevitable, and chronic illness, when health improvement is possible. PMID- 27380222 TI - Physiological and functional failure in chronic obstructive pulmonary disease, congestive heart failure and cancer: a debilitating intersection of sarcopenia, cachexia and breathlessness. AB - PURPOSE OF REVIEW: Loss of skeletal muscle mass and cachexia are important manifestations of chronic obstructive pulmonary disease and have been associated with breathlessness, functional limitation and poor prognosis. A number of other life-limiting illnesses, including cancer and chronic heart failure as well as acute conditions seen in ICU such as sepsis, are characteristically associated with cachexia and sarcopenia. These conditions may have respiratory muscle atrophy of sufficient magnitude to contribute to the development of breathlessness and associated functional limitation. The purpose of this review is to summarize findings related to a direct role for severe respiratory muscle wasting in the etiology of breathlessness in advanced, life limiting illness. RECENT FINDINGS: Localized wasting of respiratory muscles appears to be part of systemic wasting of skeletal muscles, driven by deconditioning, nutritional insufficiencies and inflammation, and because of disease-specific factors (tumor factors and exacerbations), anabolic insufficiency, autonomic dysfunction, drugs (such as corticosteroids and chemotherapy agents), mechanical ventilation and comorbidities. Marked morphological and biochemical abnormalities have been noted in diaphragm muscle biopsies. SUMMARY: Older patients with multiple comorbidities associated with muscle loss and cachexia are likely to be at elevated risk of respiratory muscle atrophy and functional loss, because of the presence of multiple, interacting etiologic factors. PMID- 27380223 TI - INCIDENCE OF ACUTE EXUDATIVE MACULOPATHY AFTER REDUCED-FLUENCE PHOTODYNAMIC THERAPY. AB - PURPOSE: To describe the incidence and features of acute exudative maculopathy (AEM) after half-fluence photodynamic therapy (PDT) and/or very minimal fluence PDT. METHODS: Retrospective chart review of all patients treated over a 7-year period. RESULTS: A total of 52 patients (58 eyes, 140 treatments) were treated with half-fluence PDT and/or very minimal fluence PDT. Patients were diagnosed with either central serous chorioretinopathy (CSCR) or neovascular age-related macular degeneration (nAMD). Two patients (1 CSCR and 1 nAMD) returned to the clinic with acute vision loss after treatment and were identified as having developed AEM. In the CSCR case, resolution occurred after intravitreal bevacizumab treatment. The nAMD case resolved with topical difluprednate treatment. We were unable to identify any risk factors for the development of AEM. CONCLUSION: AEM seems to be a rare (incidence 1.4% per treatment) and unpredictable reaction related to the proinflammatory effects of half-fluence PDT and very minimal fluence PDT. Because of the inherent limitations of this study, the true incidence of AEM after reduced-fluence PDT may be higher. PMID- 27380224 TI - Cloning of scFv from hybridomas using a rational strategy: Application as a receptor to sensitive detection microcystin-LR in water. AB - Single chain variable fragment (scFv), containing of heavy and light chains (VH and VL) joined by a short peptide linker, has been used widely for immunodetection. Nevertheless, cloning functional variable genes is still a bottle neck for the scFv generation technology. Here, a rational strategy for cloning and selecting variable region genes from an anti-microcystin-LR hybridoma was devised, then the functional VH and VL genes were recloned and assembled to scFv using splicing overlap extension PCR. The resulting scFv gene was recombinantly expressed as a soluble scFv-alkaline phosphatase fusion protein (scFv-AP) by vector PLIP6/GN. Then an indirect competitive chemiluminescent enzyme immunoassay (ic-CLEIA) for detection of microcystin-LR was developed. The half-maximum inhibition concentrations (IC50) and limits of detection (LODs, IC15) were 0.81 +/- 0.04 MUgL(-1) and 0.13 +/- 0.03 MUgL(-1), respectively. With the mean coefficient of variation lowing 8%, the mean recovery in intra-assay and inter-assay were 100.06% and 96.46%, The proposed strategy should be useful for generation scFv in a rapid and simple way. PMID- 27380225 TI - Dermal exposure to tannery effluent causes neurobehavioral changes in C57Bl/6J and Swiss mice. AB - Tannery effluents constitute highly polluting residues, which can cause negative impacts to people's health and the environment. However, studies that have investigated the effects of the exposure to these xenobiotics on the central nervous system of mammal experimental models are rare, the few that have been published focusing on the exposure via oral intake (ingestion of water containing tannery effluent concentrations). In this sense, and with the objective of expanding the knowledge beyond the neurotoxic effects observed when water contaminated by these xenobiotics is ingested, the neurobehavioral effects of dermal exposure of male C57Bl/6J and Swiss mice were analyzed. The animals were exposed to raw (wet blue-type) tannery effluent for two hours during five days, totalizing 15 days of exposure. Afterwards, the animals underwent the elevated plus-maze (predictive of anxiety) and the object recognition tests (identification of memory deficit). Our data show that the dermal exposure to the tannery effluent caused an anxiogenic behavior in these animals, when compared those that did not have direct contact with these xenobiotics. It was also observed that the animals exposed to the tannery effluent obtained lower novel object recognition indices, thus evidencing memory deficit and indicating a possible influence of the tannery effluent constituents in animal cognition. The present study attests the hypothesis that dermal exposure to tannery effluents containing neurotoxic substances causes behavioral disorders in C57Bl/6J and Swiss mice. PMID- 27380226 TI - Comparison of in vitro hormone activities of novel flame retardants TBB, TBPH and their metabolites TBBA and TBMEPH using reporter gene assays. AB - The anti-androgenic and anti-thyroid hormonal activities of the two novel brominated flame retardants, TBB and TBPH and of their metabolites TBBA and TBMEPH have been compared using the luciferase reporter gene assays. Only the parent compounds TBB and TBPH exhibited anti-glucocorticoid activity with IC50 values of 1.9 MUM and 0.3 MUM. Furthermore, mode of action for these two compounds is by direct competing to the glucocorticoid receptor (GR) with IC50 values of 0.03 MUM and 0.002 MUM. All four tested compounds possess anti androgenic and anti-thyroid hormonal activities, without agonist activities on the respective receptors. Anti-androgenic activities with IC50 values of 43.5 MUM, 0.1 MUM, 47.5 MUM and 1.3 MUM were found for TBB, TBPH, TBBA and TBMEPH. The anti-thyroid hormonal IC50 values of 37.5 MUM, 0.1 MUM, 22.8 MUM and 32.3 MUM for TBB, TBPH, TBBA and TBMEPH, together with the above quoted results, indicate that metabolism can modify anti-androgenic, anti-glucocorticoid and anti-thyroid hormonal effects of these novel brominated flame retardants. Furthermore, the parent flame retardants are shown to be able to disrupt the function of the GR as antagonists by direct competition to the receptor. PMID- 27380227 TI - Self-Healing Elastin-Bioglass Hydrogels. AB - Tailorable hydrogels that are mechanically robust, injectable, and self-healable, are useful for many biomedical applications including tissue repair and drug delivery. Here we use biological and chemical engineering approaches to develop a novel in situ forming organic/inorganic composite hydrogel with dynamic aldimine cross-links using elastin-like polypeptides (ELP) and bioglass (BG). The resulting ELP/BG biocomposites exhibit tunable gelling behavior and mechanical characteristics in a composition and concentration dependent manner. We also demonstrate self-healing in the ELP/BG hydrogels by successfully reattaching severed pieces as well as through rheology. In addition, we show the strength of genetic engineering to easily customize ELP by fusing cell-stimulating "RGD" peptide motifs. We showed that the resulting composite materials are cytocompatible as they support the cellular growth and attachment. Our robust in situ forming ELP/BG composite hydrogels will be useful as injectable scaffolds for delivering cell and drug molecules to promote soft tissue regeneration in the future. PMID- 27380228 TI - Effects of Reactive Oxygen and Temperature on the Formation of a Purple Pigment, Hordeumin, from Barley Bran-Fermented Broth. AB - A purple pigment called hordeumin, a type of anthocyanin-tannin pigment, is produced from barley barn-fermented broth. Hordeumin is a precipitate formed by storing fermented filtrate containing hordeumin precursors in an oxidative environment. Hordeumin formation was inhibited by addition of radical scavengers or antioxidants to the barley bran-fermented filtrate. The addition of iron ion accelerated hordeumin formation, and the addition of DETAPAC, an iron ion chelating reagent, influenced the color tone of hordeumin. These findings suggest that hordeumin formation may be an oxygen-mediated reaction, involving reactive oxygen species. Furthermore, hordeumin formation was accelerated by increasing the hordeumin formation temperature (from 5 to 60 degrees C). The color quality of the hordeumin that was produced at high temperature was almost the same as that hordeumin produced at 5 degrees C. PMID- 27380229 TI - One Step Synthesis of Inverted Aspartame Type Sweetener, Ac-Phe-Lys, Using Chemically Modified Chymotrypsin. AB - To search for techniques of simplified peptide synthesis, benzyloxycarbonyl chymotrypsin was prepared by a water-soluble acylating reagent and used to make Ac-Phe-Lys, an artificial peptide sweetener, which was selected as a target compound. As a result of using chemically modified chymotrypsin, Lys can be coupled directly with Ac-Phe and Ac-Phe-Lys made virtually in one step. Moreover, the total yield from preparation and purification steps for Ac-Phe-Lys was 13%. The value corresponds to that of the chemical synthesis method. On the contrary, enzymatic synthesis using native chymotrypsin cannot reach the level of the new method. It is expected that the method is more effective for simplified peptide synthesis as compared with other methods, especially on a large scale. PMID- 27380230 TI - Chemical Structure and Molecular Weights of alpha-(1->3)-D-Glucan from Lentinus edodes. AB - alpha-Glucan (L-FV-II) and beta-glucan (L-FV-I) were isolated from fruiting bodies of Lentinus edodes by extraction with 5% NaOH/0.05% NaBH4, then precipitation with 1 M acetic acid. The analysis results of Smith degradation, high-performance liquid chromatography (HPLC), infrared spectra (IR), (13)C NMR spectra, and optical rotation indicated that L-FV-II is alpha-(1->3)-D-glucan with slight (1->6) branch linkages, and L-FV-I is beta-(1->3)-D-glucan containing 10% protein, and with branches. The weight-average molecular weight, Mw, number average molecular weight, Mn, radii of gyration, (1/2), and second virial coefficients, A2, of L-FV-II in aqueous 0.5 M urea/0.5 M NaOH (obtained from diluting its solution in 1.0 M urea/1.0 M NaOH) and 0.25 M LiCl in dimethylsulfoxide (DMSO/0.25 M LiCl) were measured by light scattering, membrane osmometry, and size exclusion chromatography (SEC). The values of Mw and Mn for L FV-II in 0.5 M urea/0.5 M NaOH are 24.1*10(4) and 10.9*10(4), respectively, similar to those in DMSO/0.25 M LiCl. It was proved that strong intermolecular hydrogen bonds exist in L-FV-II, resulting in its water-insolubility, but there are not any aggregates or multiple-helix structure for L-FV-II in DMSO/0.25 M LiCl. The chain of alpha-(1->3)-D-glucan is more extended in DMSO/0.25 M LiCl than that in the aqueous solution. PMID- 27380231 TI - Enatiomeric Separation of Branched Fatty Acids after Conversion with trans-2-(2,3 Anthracenedicarboximido)cyclohexanol, a Highly Sensitive Chiral Fluorescent Conversion Reagent. AB - (1R,2R)-2-(2,3-Anthracenedicarboximido)cyclohexanol was synthesized as a highly sensitive chiral fluorescent conversion reagent. The diastereomeric derivatives of chiral branched fatty acids that had methyl ethyl chirality from the 2 to 12 position were separated into 2 peaks by reversed-phase HPLC and detected at the 10(-15) mole level by fluorometry. PMID- 27380232 TI - Purification and Characterization of Isoamyl Alcohol Oxidase ("Mureka"-Forming Enzyme). AB - Isoamyl alcohol oxidase (IAAOD) was purified to apparent homogeneity on SDS-PAGE from ultrafiltration (UF) concentrated sake. IAAOD was a glycoprotein, a monomeric protein with an apparent molecular mass of 73 and 87 kDa, by SDS-PAGE and gel filtration on HPLC, respectively. IAAOD showed high substrate specificity toward C5 branched-chain alkyl alcohol (isoamyl alcohol), and no activity toward shorter (C1-C4) or longer (C7-C10) alkyl alcohols tested. IAAOD was stable between pH 3.0-6.0 at 25 degrees C. The optimum pH was 4.5 at 35 degrees C. Heavy metal ions, p-chloromercuribenzoate (PCMB), hydrazine, and hydroxylamine strongly inhibited the enzyme activity, and an anti-oxidant like L-ascorbate did also. Isovaleraldehyde was produced markedly in pasteurized sake by adding purified IAAOD, therefore, we concluded that it was the enzyme that causes formation of mureka, an off-flavor of sake, the main component of which is isovaleraldehyde. PMID- 27380234 TI - Synthesis of the Methyl Ester of Tritium-labeled AK-toxin I, a Host-specific Toxin Produced by Alternaria alternata Japanese Pear Pathotype. AB - AK-toxin I, a host-specific toxin to Japanese pear (Pyrus serotina), was synthesized as its methyl ester from three precursor fragments: conjugated diene carboxylic acid, chiral epoxyalcohol and beta-methylphenylalanine. The epoxyalcohol fragment was derived from D-fructose, in which effective homologation of the hemiacetal carbon to alkyne by using dimethyl 1-diazo-2 oxopropylphosphonate was the key reaction. The diene-carboxylic acid fragment was prepared by repeated Wittig reactions, and was combined with the epoxyalcohol fragment by the Stille reaction. Esterification of the combined product with the stereochemically-pure beta-methylphenylalanine fragment afforded the target compound. This method was used to prepare the methyl ester of tritium-labeled AK toxin I with a specific radioactivity of 213 GBq/mmol. PMID- 27380233 TI - Erimopyrone, a Lignan Derivative from the Liverwort Moerckia erimona. AB - The new lignan derivative, erimopyrone, was isolated from the liverwort, Moerckia erimona. Its structure was established as [1R, 2S]-1(6-carboxy-2-oxo-2H-4 pyranyl)- 6,7-dihydroxy-1,2-dihydro-2,3-naphthalenedicarboxylic acid by spectroscopic methods. PMID- 27380235 TI - Production of (S,S)-Ethylenediamine-N,N'-disuccinic Acid from Ethylenediamine and Fumaric Acid by Bacteria. AB - We tried to produce (S,S)-ethylenediamine-N,N'-disuccinic acid [(S,S)-EDDS] with the aid of microorganisms that can degrade the compound. A reaction mixture consisting of ethylenediamine and fumaric acid was incubated with the bacteria isolated from soil and sludge, and we found that several kinds of bacteria such as Sphingomonas, Brevundimonas, Pseudomonas, and Acidovorax produced (S,S)-EDDS. The optimum pH and the temperature for the production was pH 7.5 and 35 degrees C for Acidovorax sp. TNT149 and the bacterial cells produced 90 mmoles of (S,S) EDDS from 200 mmoles of ethylenediamine and 350 mmoles of fumaric acid under these reaction condition. PMID- 27380236 TI - Glutamate Overproduction in Corynebacterium glutamicum Triggered by a Decrease in the Level of a Complex Comprising DtsR and a Biotin-containing Subunit. AB - Glutamate overproduction in Corynebacterium glutamicum is induced by Tween 40, biotin-limitation, or sublethal amounts of penicillin. Disruption of the dtsR gene, which encodes a putative component of a biotin-containing enzyme complex involved in fatty acid synthesis, causes constitutive overproduction of glutamate. We report here that overexpression of dtsR inhibits the induction of glutamate overproduction. In contrast, the level of DtsR in the wild type strain was found to decrease in the presence of Tween 40 or limited amounts of biotin. Tween 40, biotin-limitation, or dtsR disruption also reduced the activity of 2 oxoglutarate dehydrogenase complex (ODHC), which is involved in the synthesis of succinate from 2-oxoglutarate. These results indicate that decrease in the level of DtsR or a complex containing DtsR triggers the increased synthesis of glutamate from 2-oxoglutarate by lowering the ODHC activity. PMID- 27380237 TI - Novel Synthesis of (-)-Bestatin from L-Aspartic Acid. AB - Oxazoline-4-acetate derivative 3 that could be readily obtained from L-aspartic acid was subjected to highly stereoselective hydroxylation, and subsequent Mitsunobu inversion of the hydroxyl group led to (2S,3R)-3-amino-3-benzyl-2 hydroxybutanoic acid derivative 8 in a good yield. Coupling of 8 with L-leucine benzyl ester and subsequent cleavage of the protective groups provided (-) bestatin 1 in a high yield. PMID- 27380238 TI - Positional Isomers of Monohydroperoxides Produced by Peroxidation of Phosphatidylcholine Containing an Arachidonoyl Moiety in a Liposomal Suspension. AB - Monohydroperoxides derived from the peroxidation of 1-palmitoyl-2-arachidonoyl phosphatidylcholine (PC-AA) in a liposomal suspension had a characteristic isomeric composition. Of the two possible isomers derived from a pentadienyl radical intermediate, the isomer with a hydroperoxy group on the carboxyl terminal side was at a substantially lower level than the other. PMID- 27380239 TI - Apolipoprotein B mRNA Editing in the Liver and Small Intestine of Rats Fed on Beet Fiber, Soy Protein, and Fish Oil. AB - Apolipoprotein B mRNA editing was investigated in the liver and small intestine of rats fed on beet fiber, soy protein, or fish oil as plasma cholesterol reducing agents. The diets had no influence on the editing in both the liver and intestine, despite their cholesterol-lowering action. The results suggest that apo B mRNA editing is not involved in the cholesterol-lowering effect of these diets. PMID- 27380240 TI - Momilactones A and B in Rice Straw Harvested at Different Growth Stages. AB - Momilactones A and B in rice straw harvested at different growth stages were quantified by HPLC-MS-MS. They increased to their maximal levels at the heading stage and then gradually decreased. In addition, these phytotoxins were found to be relatively easily extracted with water. PMID- 27380241 TI - Genetic alterations of delta-catenin/NPRAP/Neurojungin (CTNND2): functional implications in complex human diseases. AB - Some genes involved in complex human diseases are particularly vulnerable to genetic variations such as single nucleotide polymorphism, copy number variations, and mutations. For example, Ras mutations account for over 30 % of all human cancers. Additionally, there are some genes that can display different variations with functional impact in different diseases that are unrelated. One such gene stands out: delta-catenin/NPRAP/Neurojungin with gene designation as CTNND2 on chromosome 5p15.2. Recent advances in genome wide association as well as molecular biology approaches have uncovered striking involvement of delta catenin gene variations linked to complex human disorders. These disorders include cancer, bipolar disorder, schizophrenia, autism, Cri-du-chat syndrome, myopia, cortical cataract-linked Alzheimer's disease, and infectious diseases. This list has rapidly grown longer in recent years, underscoring the pivotal roles of delta-catenin in critical human diseases. delta-Catenin is an adhesive junction-associated protein in the delta subfamily of the beta-catenin superfamily. delta-Catenin functions in Wnt signaling to regulate gene expression and modulate Rho GTPases of the Ras superfamily in cytoskeletal reorganization. delta-Catenin likely lies where Wnt signaling meets Rho GTPases and is a unique and vulnerable common target for mutagenesis in different human diseases. PMID- 27380244 TI - ARPP-19 promotes proliferation and metastasis of human glioma. AB - Glioma is the most common and aggressive type of human primary brain tumor with a poor outcome. The molecular mechanisms underlying glioma development and progression are still poorly understood. Recent studies have reported a novel role of ARPP-19 in the regulation of cell mitosis and cancer progression. However, no study has been carried out to determine the role of ARPP-19 in human glioma cells and assess the expression and clinical significance of ARPP-19 in human glioma. In this study, we systematically examined the role of ARPP-19 in glioma A172 cells and examined the expression of ARPP-19 and CD147 in 81 cases of human glioma tissue specimens and correlated them to clinicopathological parameters and patient survival. We found that ARPP-19 promoted both proliferation and metastasis of human glioma cells and the expression of ARPP-19 and CD147 in high-grade glioma was significantly higher than that in the low grade glioma. Patients whose tumors were positive for expression of ARPP-19 or CD147 showed lower relapse-free survival and overall survival than patients whose tumors were negative for ARPP-19 or CD147, respectively. Pearson correlation analysis indicated that there was a statistically significant correlation between ARPP-19 and CD147. Expressions of ARPP-19 and CD147 may serve as biomarkers for high-grade glioma and poor patient survival. PMID- 27380243 TI - The C677T variant in MTHFR modulates associations between blood-based and cerebrospinal fluid biomarkers of neurodegeneration. AB - The C677T functional variant in the methylene-tetrahydrofolate reductase (MTHFR) gene results in reduced enzymatic activity and elevated blood levels of homocysteine. Plasma levels of apolipoprotein E (ApoE) are negatively correlated with cerebral amyloid burden, but plasma homocysteine concentrations are associated with increased amyloid-beta (Abeta) deposition in the brain. Here, we sought to determine whether associations between low plasma ApoE levels and elevated in-vivo amyloid burden were modulated by carrying the C677T variant. We tested this hypothesis in a large sample of elderly participants from the Alzheimer's Disease Neuroimaging Initiative. We used general linear models to examine associations between plasma homocysteine concentrations, circulating ApoE levels, cerebrospinal fluid concentrations of Abeta, and their modulation by MTHFR and ApoE genotype. Age, sex, and dementia status were included as covariates in all analyses. Higher circulating levels of ApoE predicted increased cerebrospinal fluid concentrations of Abeta, indicating lower in-vivo burden, in C-allele carriers, but not in homozygotes at the C677T variant, who showed significant elevations in plasma homocysteine levels. This modulation by the MTHFR genotype did not remain significant after controlling for ApoE genotype. In T-homozygotes who do not carry the ApoE-epsilon4 allele, the relationship between low plasma ApoE levels and an increased risk of dementia is likely obscured by the presence of elevated plasma homocysteine. This report suggests the value of genotyping patients at the C677T functional variant when using plasma ApoE levels as a preclinical biomarker for Alzheimer's disease. PMID- 27380242 TI - Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry. AB - MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR = 0.69, 95 % CI: 0.55-0.88, P = 0.003), ESR1 rs523736 (OR = 0.88, 95 % CI: 0.82-0.95, P = 3.99 * 10(-4)), and ZCCHC11 rs114101502 (OR = 1.33, 95 % CI: 1.11-1.59, P = 0.002), and one SNP in primary miRNA sequence (rs116159732 in miR-6826, OR = 0.74, 95 % CI: 0.63-0.89, P = 0.001) were found to have significant associations in both discovery and validation phases. In a subgroup analysis, two SNPs were associated with risk of estrogen receptor (ER)-negative breast cancer, and three SNPs were associated with risk of ER-positive breast cancer. Several variants in miRNA and miRNA biogenesis pathway genes were associated with breast cancer risk. Risk associations varied by ER status, suggesting potential new mechanisms in etiology. PMID- 27380246 TI - [Not Available]. PMID- 27380245 TI - [Not Available]. PMID- 27380247 TI - [Not Available]. PMID- 27380248 TI - [Not Available]. PMID- 27380249 TI - [Not Available]. PMID- 27380250 TI - [Not Available]. PMID- 27380252 TI - [Not Available]. PMID- 27380251 TI - [Not Available]. PMID- 27380253 TI - Efficacy of Methylprednisolone Pulse Followed by Oral Prednisone in Birdshot Chorioretinopathy. AB - PURPOSE: To report the outcomes of initial methylprednisolone pulse then oral prednisone in the treatment of birdshot chorioretinopathy (BSCR). METHODS: We retrospectively reviewed medical records of 21 BSCR patients, treated with initial methylprednisolone, prednisone, or immunosuppressive therapy. Main outcome measures were changes in visual acuity, intraocular inflammation, concomitant immunosuppressive drug or intravitreal steroid, and adverse events. RESULTS: In total, 14 patients were initially treated with methylprednisolone; four patients with prednisone; and three with immunosuppressive drug. Intraocular inflammation was controlled in 10 of 14 patients (71%) at 1 year, with a mean dose of 6.2 mg/day prednisone. Patients treated initially by methylprednisolone had improved visual acuity at 1 year, but it was not significantly different from patients treated initially by prednisone. CONCLUSIONS: Corticosteroid therapy, including initial methylprednisolone pulse then prednisone, was effective in stabilizing vision and decreasing inflammation in most patients with BSCR. PMID- 27380254 TI - Identification of Effects of Regulatory Actions on Air Quality in Goods Movement Corridors in California. AB - Few studies have assessed the impact of regulatory actions on air quality improvement through a comprehensive monitoring effort. In this study, we designed saturation sampling of nitrogen oxides (NOX) for the counties of Los Angeles and Alameda (San Francisco Bay) before (2003-2007) and after (2008-2013) implementation of goods movement actions in California. We further separated the research regions into three location categories, including goods movement corridors (GMCs), nongoods movement corridors (NGMCs), and control areas (CTRLs). Linear mixed models were developed to identify whether reductions in NOX were greater in GMCs than in other areas, after controlling for potential confounding, including weather conditions (e.g., wind speed and temperature) and season of sampling. We also considered factors that might confound the relationship, including traffic and cargo volumes that may have changed due to economic downturn impacts. Compared to the pre-policy period, we found reductions of average pollutant concentrations for nitrogen dioxide (NO2) and NOX in GMCs of 6.4 and 21.7 ppb. The reductions were smaller in NGMCs (5.9 and 16.3 ppb, respectively) and in CTRLs (4.6 and 12.1 ppb, respectively). After controlling for potential confounding from weather conditions, season of sampling, and the economic downturn in 2008, the linear mixed models demonstrated that reductions in NO2 and NOX were significantly greater in GMCs compared to reductions observed in CTRLs; there were no statistically significant differences between NGMCs and CTRLs. These results indicate that policies regulating goods movement are achieving the desired outcome of improving air quality for the state, particularly in goods movement corridors where most disadvantaged communities live. PMID- 27380255 TI - Correction: The Risk of Peripheral Arterial Disease after Parathyroidectomy in Patients with End-Stage Renal Disease. AB - [This corrects the article DOI: 10.1371/journal.pone.0156863.]. PMID- 27380256 TI - The use of a negative pressure wound management system in perineal wound closure after extralevator abdominoperineal excision (ELAPE) for low rectal cancer. AB - BACKGROUND: Perineal wound healing is a significant challenge after extralevator abdominoperineal excision (ELAPE) due to a high rate of wound breakdown. Negative pressure therapy has proven benefits in open wounds, and recently a negative pressure system has been developed for use on closed wounds at high risk of breakdown, such as apronectomy and hysterectomy. The aim of the present study was to determine whether negative pressure therapy applied to closed perineal wounds after ELAPE improved wound healing and compare outcomes to the published literature and outcomes from a historical cohort of patients who had undergone 'standard' abdominoperineal resection (APR) and primary closure of the perineal wounds. METHODS: Prospective data on consecutive patients having ELAPE in the period from November 2012 to April 2015 were collected. The pelvic floor defect was reconstructed with biologic mesh. The adipose tissue layer was closed with vicryl sutures, a suction drain was left in the deep layer, the subcuticular layer and skin were closed, and the negative pressure system was applied. Any wound breakdown within the first 30 days postoperatively was recorded. RESULTS: Of the 32 consecutive ELAPE patients whose perineal wounds were closed within 30 days with the use of the negative pressure system, there was 1 patient with major perineal wound breakdown and 2 patients with a 1 cm superficial wound defect, which needed no further treatment. In the remaining 29 (90 %) patients, the perineal wounds healed fully without complications. Twenty-five patients underwent standard APR in 2010-2011 with primary closure of their perineal wounds. Ten out of 25(40 %) of patients who had undergone standard APR and primary closure of perineal wounds had major wound complications (p = 0.01). CONCLUSIONS: Our results suggest that after ELAPE the application of a negative pressure system to the perineal wound closed with biologic mesh may reduce perineal wound complications and may reduce the need for major perineal reconstruction. PMID- 27380257 TI - Results of long-term retrograde rectal cleansing in patients with constipation or fecal incontinence. AB - BACKGROUND: The aim of the present study was to determine the success rate, quality of life and predictive factors of success associated with long-term rectal cleansing (RC) for defecatory disorders. METHODS: All patients who started RC between January 2010 and August 2014 in our referral hospital were sent questionnaires concerning actual RC, Short Form 36 Health Survey (SF-36), Fecal Incontinence Quality of Life (FI-QoL) and the Beck Depression Inventory (BDI). In addition, they were contacted in May and December 2015 for further follow-up information. RESULTS: Eighty-six patients were offered RC, and 60 patients (45 women, 15 men) started RC. Thirty-three (55 %) patients stopped RC after a median time of 6 months. Twenty-seven (45 %) continued for a median time of 12 months. Forty-three (72 %) patients responded to the questionnaires. SF-36 showed that patients still using RC had more energy and were less fatigued than patients who discontinued therapy. No significant difference was found between patients who stopped and continued RC concerning age, gender, defecation disturbance, underlying disorders, anorectal function, colon-transit time, FI-QoL or BDI score. Twenty-three patients (38 %) were still performing RC after 21 months, 22 patients (37 %) after 28 months and 1 patient was lost to follow-up. CONCLUSIONS: RC is a moderately effective long-term alternative in patients who do not respond to medical therapy and biofeedback exercises. There is a high dropout rate in the first months, but a moderate rate of continuation in the period hereafter. No predictive factors for continuation were found in medical history or function tests. Those who continued RC performed better on the SF-36 subscale energy/fatigue. PMID- 27380258 TI - From TATA to NOTES, how taTME fits into the evolutionary surgical tree. PMID- 27380259 TI - Stent Retrievers for Treating Anterior Circulation Acute Ischemic Stroke. PMID- 27380260 TI - Promoter Screening from Bacillus subtilis in Various Conditions Hunting for Synthetic Biology and Industrial Applications. AB - The use of Bacillus subtilis in synthetic biology and metabolic engineering is highly desirable to take advantage of the unique metabolic pathways present in this organism. To do this, an evaluation of B. subtilis' intrinsic biological parts is required to determine the best strategies to accurately regulate metabolic circuits and expression of target proteins. The strengths of promoter candidates were evaluated by measuring relative fluorescence units of a green fluorescent protein reporter, integrated into B. subtilis' chromosome. A total of 84 predicted promoter sequences located upstream of different classes of proteins including heat shock proteins, cell-envelope proteins, and proteins resistant against toxic metals (based on similarity) and other kinds of genes were tested. The expression levels measured ranged from 0.0023 to 4.53-fold of the activity of the well-characterized strong promoter P43. No significant shifts were observed when strains, carrying different promoter candidates, were cultured at high temperature or in media with ethanol, but some strains showed increased activity when cultured under high osmotic pressure. Randomly selected promoter candidates were tested and found to activate transcription of thermostable beta galactosidase (bgaB) at a similar level, implying the ability of these sequences to function as promoter elements in multiple genetic contexts. In addition, selected promoters elevated the final production of both cytoplasmic bgaB and secreted protein alpha-amylase to about fourfold and twofold, respectively. The generated data allows a deeper understanding of B. subtilis' metabolism and will facilitate future work to develop this organism for synthetic biology. PMID- 27380263 TI - Structural Analysis of Human Argonaute-2 Bound to a Modified siRNA Guide. AB - Incorporation of chemical modifications into small interfering RNAs (siRNAs) increases their metabolic stability and improves their tissue distribution. However, how these modifications impact interactions with Argonaute-2 (Ago2), the molecular target of siRNAs, is not known. Herein we present the crystal structure of human Ago2 bound to a metabolically stable siRNA containing extensive backbone modifications. Comparison to the structure of an equivalent unmodified-siRNA complex indicates that the structure of Ago2 is relatively unaffected by chemical modifications in the bound siRNA. In contrast, the modified siRNA appears to be much more plastic and shifts, relative to the unmodified siRNA, to optimize contacts with Ago2. Structure-activity analysis reveals that even major conformational perturbations in the 3' half of the siRNA seed region have a relatively modest effect on knockdown potency. These findings provide an explanation for a variety of modification patterns tolerated in siRNAs and a structural basis for advancing therapeutic siRNA design. PMID- 27380264 TI - Incidence and Outcomes of Acute Kidney Injury Requiring Renal Replacement Therapy: A Retrospective Cohort Study. AB - BACKGROUND: Incidence of acute kidney injury (AKI), requiring dialysis, is on the rise globally and is associated with high mortality and morbidity. AIM: This study is aimed at examining the incidence of AKI requiring renal replacement therapy (RRT) in the Tayside region of Scotland and the impact of RRT for AKI on morbidity, mortality and length of hospital stay. METHODS: One hundred seventy eight patients (>18 years of age) who received acute RRT between January 1, 2012 and December 31, 2012 were retrospectively selected for inclusion in the longitudinal cohort study. Incidence rate was calculated. Length of hospital stay, likely cause of AKI, renal recovery and mortality data were collected for a follow-up period of 1 year or until death. Chi-square test was used to compare the morbidity and mortality data between subgroups. RRT-free survival and time until-event (death or RRT) analysis was performed using Kaplan-Meier plots. Cox regression was used to examine the relationship between age, sex, diabetes and chronic kidney disease (CKD) on survival. RESULTS: Incidence of AKI requiring RRT was 430 per million population per year. Median length of hospital stay was 21 days. In-patient mortality was 36%, mortality at 90 days was 44% and at 1 year 54%. Median time from start of RRT until death or chronic RRT was 90 days (95% CI 14-166). One-year cumulative RRT-free survival was 26% in the ward, 36% in high dependency units and 48% in intensive care unit subgroups. Diabetes, gender and CKD at baseline did not affect RRT-free survival in the cohort being studied. A quarter of the cohort regained full renal function and 15% of survivors were on a chronic dialysis programme at 1 year. CONCLUSIONS: This study gives a comprehensive summary of renal outcomes and mortality after a single episode of AKI requiring RRT. The findings of the study confirm that dialysis-dependent AKI is associated with increased length of hospital stay, high mortality and loss of renal function long term, emphasizing the importance of recognition, classification and prevention of AKI. PMID- 27380261 TI - Unique Behavioral and Neurochemical Effects Induced by Repeated Adolescent Consumption of Caffeine-Mixed Alcohol in C57BL/6 Mice. AB - The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61) exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug reward and cross-sensitivity, and natural reward. To determine changes in neurological activity resulting from adolescent exposure, we monitored changes in expression of the transcription factor DeltaFosB in the dopaminergic reward pathway as a sign of long-term increases in neuronal activity. Repeated adolescent exposure to caffeine-mixed alcohol exposure induced significant locomotor sensitization, desensitized cocaine conditioned place preference, decreased cocaine locomotor cross-sensitivity, and increased natural reward consumption. We also observed increased accumulation of DeltaFosB in the nucleus accumbens following repeated adolescent caffeine-mixed alcohol exposure compared to alcohol or caffeine alone. Using our exposure model, we found that repeated exposure to caffeine-mixed alcohol during adolescence causes unique behavioral and neurochemical effects not observed in mice exposed to caffeine or alcohol alone. Based on similar findings for different substances of abuse, it is possible that repeated exposure to caffeine-mixed alcohol during adolescence could potentially alter or escalate future substance abuse as means to compensate for these behavioral and neurochemical alterations. PMID- 27380262 TI - Selective Pro-Apoptotic Activity of Novel 3,3'-(Aryl/Alkyl-Methylene)Bis(2 Hydroxynaphthalene-1,4-Dione) Derivatives on Human Cancer Cells via the Induction Reactive Oxygen Species. AB - Selective induction of apoptosis in cancer cells barring the normal cells is considered as an effective strategy to combat cancer. In the present study, a series of twenty-two (22) synthetic 3,3'-(aryl/alkyl-methylene)bis(2 hydroxynaphthalene-1,4-dione) bis-lawsone derivatives were assayed for their pro apoptotic activity in six different cell lines (five cancerous and one normal) using MTT assay. Out of these 22 test compounds, 1j was found to be the most effective in inducing apoptosis in human glioma cells (CCF-4) among the different cell lines used in the study. The activity of this compound, 1j, was then compared to a popular anticancer drug, cisplatin, having limited usage because of its nephrotoxic nature. In this study, 1j derivative showed much less toxicity to the normal kidney cells compared to cisplatin, thus indicating the superiority of 1j as a possible anticancer agent. This compound was observed to induce apoptosis in the glioma cells by inducing the caspase dependent apoptotic pathways via ROS and downregulating the PI3K/AKT/mTOR pathway. Estimation of different oxidative stress markers also confirms the induction of oxidative stress in 1j exposed cancer cells. The toxicity of 1j compound toward cancer cells was confirmed further by different flow cytometrical analyses to estimate the mitochondrial membrane potential and cell cycle. The sensitivity of malignant cells to apoptosis, provoked by this synthetic derivative in vitro, deserves further studies in suitable in vivo models. These studies not only identified a novel anticancer drug candidate but also help to understand the metabolism of ROS and its application in cancer treatment. PMID- 27380266 TI - Parental practices of Italian mothers and fathers during early infancy: The role of knowledge about parenting and child development. AB - Our contribution aims to verify whether parental knowledge about child development and parenting constitutes a protective factor in the application of dysfunctional educational practices. Numerous studies have found that parental knowledge has a great influence on parenting, however it remains unclear whether both are casually linked in a direct and linear way. Data currently available on parental knowledge almost exclusively refers to mothers and subjects at risk. Furthermore, there are almost no studies which take into consideration subjects who are Italian citizens. In contrast our work takes into consideration a normative sample of 157 Italian couples who are the parents of children aged between 16 and 36 months and who completed the Knowledge of Infant Development Inventory (KIDI; MacPhee, 1981) and the Parenting Scale (Arnold, O'Leary, Wolff, & Acker, 1993). The results highlight differences between mothers and fathers, both in terms of knowledge levels (higher for mothers) and educational practices (maternal practices are more frequently dysfunctional); knowledge influences educational practices above all in the case of fathers, although said effect is slight, which supports the idea that interaction between knowledge and parental practices is not linear but rather mediated by other factors. PMID- 27380265 TI - Selection on Network Dynamics Drives Differential Rates of Protein Domain Evolution. AB - The long-held principle that functionally important proteins evolve slowly has recently been challenged by studies in mice and yeast showing that the severity of a protein knockout only weakly predicts that protein's rate of evolution. However, the relevance of these studies to evolutionary changes within proteins is unknown, because amino acid substitutions, unlike knockouts, often only slightly perturb protein activity. To quantify the phenotypic effect of small biochemical perturbations, we developed an approach to use computational systems biology models to measure the influence of individual reaction rate constants on network dynamics. We show that this dynamical influence is predictive of protein domain evolutionary rate within networks in vertebrates and yeast, even after controlling for expression level and breadth, network topology, and knockout effect. Thus, our results not only demonstrate the importance of protein domain function in determining evolutionary rate, but also the power of systems biology modeling to uncover unanticipated evolutionary forces. PMID- 27380267 TI - Clostridial Binary Toxins: Basic Understandings that Include Cell Surface Binding and an Internal "Coup de Grace". AB - Clostridium species can make a remarkable number of different protein toxins, causing many diverse diseases in humans and animals. The binary toxins of Clostridium botulinum, C. difficile, C. perfringens, and C. spiroforme are one group of enteric-acting toxins that attack the actin cytoskeleton of various cell types. These enterotoxins consist of A (enzymatic) and B (cell binding/membrane translocation) components that assemble on the targeted cell surface or in solution, forming a multimeric complex. Once translocated into the cytosol via endosomal trafficking and acidification, the A component dismantles the filamentous actin-based cytoskeleton via mono-ADP-ribosylation of globular actin. Knowledge of cell surface receptors and how these usurped, host-derived molecules facilitate intoxication can lead to novel ways of defending against these clostridial binary toxins. A molecular-based understanding of the various steps involved in toxin internalization can also unveil therapeutic intervention points that stop the intoxication process. Furthermore, using these bacterial proteins as medicinal shuttle systems into cells provides intriguing possibilities in the future. The pertinent past and state-of-the-art present, regarding clostridial binary toxins, will be evident in this chapter. PMID- 27380268 TI - Receptors and Binding Structures for Clostridium difficile Toxins A and B. AB - Two characteristics of toxins A and B from C. difficile (TcdA, TcdB) are important for the understanding of the pathogenic effect of these homologous toxins. First, these toxins are huge single-chain but multidomain proteins that display their action intracellularly within the cytosol of host cells. And second, albeit various cell types highly differ in their sensitivity toward these toxins, no toxin-resistant cell type has been described yet. Investigation of receptor-mediated uptake of these toxins is very ambitious. It demands discrimination between cell surface binding, interaction with more than one functional receptor responsible for uptake as well as other functional receptors that recognize bacterial pathogens and are not necessarily related with endocytosis. The current understanding of a complex uptake process is that TcdB interacts with at least two facultative receptors that mediate entry into host cells by redundant endocytotic pathways. Although both homologous toxins do obviously not share the same receptors, this principle of redundant binding domains found for TcdB does also account for TcdA. PMID- 27380269 TI - Staphylococcus aureus-Associated Musculoskeletal Infections. AB - Musculoskeletal infections caused by Staphylococcus aureus are among the most difficult-to-treat infections. S. aureus osteomyelitis is associated with a tremendous disease burden through potential for long-term relapses and functional deficits. Although considerable advances have been achieved in diagnosis and treatment of osteomyelitis, the management remains challenging and impact on quality of life is still enormous. S. aureus acute arthritis is relatively seldom in general population, but the incidence is considerably higher in patients with predisposing conditions, particularly those with rheumatoid arthritis. Rapidly destructive course with high mortality and disability rates makes urgent diagnosis and treatment of acute arthritis essential. S. aureus pyomyositis is a common disease in tropical countries, but it is very seldom in temperate regions. Nevertheless, the cases have been increasingly reported also in non-tropical countries, and the physicians should be able to timely recognize this uncommon condition and initiate appropriate treatment. The optimal management of S. aureus associated musculoskeletal infections requires a strong interdisciplinary collaboration between all involved specialists. PMID- 27380270 TI - Self-directed simulation-based training of emergency cricothyroidotomy: a route to lifesaving skills. AB - The emergency cricothyroidotomy (EC) is a critical procedure. The high cost of failures increases the demand for evidence-based training methods. The aim of this study was to present and evaluate self-directed video-guided simulation training. Novice doctors were given an individual 1-h simulation training session. One month later, an EC on a cadaver was performed. All EC's were video recorded. An assessment tool was used to rate performance. Performance was compared with a pass/fail level for the EC. We found a high reliability, based on Pearson's r (0.88), and a significant progression of skill during training (p < 0.001). Eleven out of 14 succeeded in creating an airway on the cadaver in 64 s (median, range 39-86 s), but only four achieved a passing score. Our 1-h training protocol successfully raised the competence level of novice doctors; however, the training did not ensure that all participants attained proficiency. PMID- 27380271 TI - Intraperitoneal mesenchymal stem cell administration ameliorates allergic rhinitis in the murine model. AB - Previous studies showed that bone marrow-derived mesenchymal stem cells (BMSCs) could ameliorate a variety of immune-mediated and inflammatory diseases due to their immunomodulatory and anti-inflammatory effects. In this study, we developed a mouse model of ovalbumin (OVA) induced allergic inflammation in the upper airways and evaluated the effects of the intraperitoneal administration of BMSCs on allergic inflammation. Twenty-five BALB/c mice were divided into five groups; group I (control group), group II (sensitized and challenged with OVA and treated with saline-placebo group), group III (sensitized and challenged with OVA and treated with 1 * 106 BMSCs), group IV (sensitized and challenged with OVA and treated with 2 * 106 BMSCs), and group V (sensitized and challenged with phosphate buffered saline (PBS) and treated with 1 * 106 BMSCs). Histopathological features (number of goblet cells, eosinophils and mast cells, basement membrane, epithelium thickness, and subepithelial smooth muscle thickness) of the upper and lower airways and BMSCs migration to nasal and lung tissue were evaluated using light and confocal microscopes. Levels of cytokines in the nasal lavage fluid and lung tissue supernatants were measured using enzyme linked immunosorbent assay (ELISA). Confocal microscopic analysis showed that there was no significant amount of BMSCs in the nasal and lung tissues of group V. However, significant amount of BMSCs were observed in group III and IV. In OVA induced AR groups (group II, III, and IV), histopathological findings of chronic asthma, such as elevated subepithelial smooth muscle thickness, epithelium thickness, and number of goblet and mast cells, were determined. Furthermore, the number of nasal goblet and eosinophil cells, histopathological findings of chronic asthma, and IL-4, IL-5, IL-13, and NO levels was significantly lower in both BMSCs-treated groups compared to the placebo group. Our findings indicated that histopathological findings of chronic asthma were also observed in mice upon AR induction. BMSCs migrated to the nasal and lung tissues following intraperitoneal delivery and ameliorated to the airway remodeling and airway inflammation both in the upper and lower airways via the inhibition of T helper (Th) 2 immune response in the murine model of AR. PMID- 27380272 TI - Jugulotympanic paragangliomas in southern Finland: a 40-year experience suggests individualized surgical management. AB - Treatment of jugulotympanic paragangliomas (JTPGLs) remains challenging with no clear guidelines for management or follow-up. The aim of this retrospective case note study was to assess long-term results of operatively and conservatively managed JTPGLs between years 1974-2013. A total of 36 patients with JTPGLs were identified. Clinical characteristics and management outcomes of patients were reviewed. Data were extracted on demographics, symptoms, timing of diagnosis, tumor location and size, embolization, and management, including pre- and post operative imaging, analysis of operative techniques, and follow-up. Pulsatile tinnitus and hearing loss were the most common presenting symptoms. Thirty-four (94 %) patients were treated with primary surgical therapy and two (6 %) with radiotherapy. The surgical approaches included endaural approach for Fisch Class A tumors and a variety of approaches for Fisch Class B-D tumors with an increasing predilection for function-preserving surgery. Eight (24 %) patients received subtotal resection. Five (15 %) patients had a local recurrence within 10 years after primary surgery. Two (6 %) patients suffered a permanent cranial nerve (CN) deficit after primary surgery. We advocate radical surgery when tumor resection is possible without compromising CNs. Function-preserving surgery with at least a 10-year follow-up for Fisch Class B-D tumors should be considered if CNs are in danger. PMID- 27380273 TI - Noncovalent Pi-Pi Stacking at the Carbon-Electrolyte Interface: Controlling the Voltage Window of Electrochemical Supercapacitors. AB - A key parameter in the operation of an electrochemical double-layer capacitor is the voltage window, which dictates the device energy density and power density. Here we demonstrate experimental evidence that pi-pi stacking at a carbon-ionic liquid interface can modify the operation voltage of a supercapacitor device by up to 30%, and this can be recovered by steric hindrance at the electrode electrolyte interface introduced by poly(ethylene oxide) polymer electrolyte additives. This observation is supported by Raman spectroscopy, electrochemical impedance spectroscopy, and differential scanning calorimetry that each independently elucidates the signature of pi-pi stacking between imidazole groups in the ionic liquid and the carbon surface and the role this plays to lower the energy barrier for charge transfer at the electrode-electrolyte interface. This effect is further observed universally across two separate ionic liquid electrolyte systems and is validated by control experiments showing an invariant electrochemical window in the absence of a carbon-ionic liquid electrode electrolyte interface. As interfacial or noncovalent interactions are usually neglected in the mechanistic picture of double-layer capacitors, this work highlights the importance of understanding chemical properties at supercapacitor interfaces to engineer voltage and energy capability. PMID- 27380274 TI - Contextual modulation of hippocampal activity during picture naming. AB - Picture naming is a standard task used to probe language processes in healthy and impaired speakers. It recruits a broad neural network of language related areas, among which the hippocampus is rarely included. However, the hippocampus could play a role during picture naming, subtending, for example, implicit learning of the links between pictured objects and their names. To test this hypothesis, we recorded hippocampal activity during plain picture naming, without memorization requirement; we further assessed whether this activity was modulated by contextual factors such as repetition priming and semantic interference. Local field potentials recorded from intracerebral electrodes implanted in the healthy hippocampi of epileptic patients revealed a specific and reliable pattern of activity, markedly modulated by repetition priming and semantic context. These results indicate that the hippocampus is recruited during picture naming, presumably in relation to implicit learning, with contextual factors promoting differential hippocampal processes, possibly subtended by different sub circuitries. PMID- 27380275 TI - The C-Terminal Fragment of Agrin (CAF), a Novel Marker of Renal Function, Is Filtered by the Kidney and Reabsorbed by the Proximal Tubule. AB - Agrin, a multidomain proteoglycan and neurotrypsin, a neuronal serine protease, are important for forming (neuromuscular) synapses. Proteolytical activity of neurotrypsin produces a C-terminal fragment of agrin, termed CAF, of approximately 22 kDA molecular size which also circulates in blood. The presence of CAF in urine suggests either glomerular filtration or secretion into urine. Blood levels of CAF have been identified as a potential novel marker of kidney function. Here we describe that several nephron segments in the mouse kidney express agrin and neutrotrypsin in addition to the localization of both protein in the glomerulum. Agrin mRNA and protein was detected in almost all nephron segments and mRNA abundance was highest in the inner medullary collecting duct. Neurotrypsin mRNA was mostly detected in the thick ascending limb of the loop of Henle, the distal convoluted tubule, and the inner medullary collecting duct. Moreover, we show that the proximal tubule absorbs injected recombinant CAF by a process shared with receptor-mediated and fluid phase endocytosis. Co-injection of CAF with recombinant human transferrin, a substrate of the receptor-mediated endocytic pathway as well as with FITC-labelled dextran (10 kDa), a marker of fluid phase endocytosis, showed partial colocalization of CAF with both markers. Further colocalization of CAF with the lysosomal marker cathepsin B suggested degradation of CAF by the lysosome in the proximal tubule. Thus, the murine kidney expresses agrin and neurotrypsin in nephron segments beyond the glomerulum. CAF is filtered by the glomerulum and is reabsorbed by endocytosis by the proximal tubule. Thus, impaired kidney function could impair glomerular clearance of CAF and thereby increase circulating CAF levels. PMID- 27380277 TI - Clinical Faceoff: Distal Biceps Rupture: Operative Versus Nonoperative Treatment. PMID- 27380276 TI - Simultaneous Determination of Multiple microRNA Levels Utilizing Biotinylated Dideoxynucleotides and Mass Spectrometry. AB - MicroRNAs (miRNAs) are important regulators of gene translation and have been suggested as potent biomarkers in various disease states. In this study, we established an efficient method for simultaneous determination of multiple miRNA levels, employing the previously developed SPC-SBE (solid phase capture-single base extension) approach and MALDI-TOF mass spectrometry (MS). In this approach, we first perform reverse transcription of miRNAs extracted using stem-loop primers. Then the cDNA is co-amplified with competitors, synthetic oligonucleotides whose sequences precisely match cDNA except for one base, and the amplicons serve as templates for a multiplexed SBE reaction. Extension products are isolated using SPC and quantitatively analyzed with MALDI-TOF MS to determine multiple miRNA levels. Here we demonstrated concurrent analysis of four miRNA levels utilizing the approach. Furthermore, we showed the presented method significantly facilitated MS analysis of peak area ratio owing to SPC. The SPC process allowed effective removal of irrelevant reaction components prior to MS and promoted MS sample purification. Data obtained in this study was verified with RT-qPCR and agreement was shown on one order of magnitude scale, suggesting the SPC-SBE and MS approach has strong potential as a viable tool for high throughput miRNA analysis. PMID- 27380278 TI - CORR Insights((r)): Periprosthetic Joint Infection in Hip Arthroplasty: Is There an Association Between Infection and Bearing Surface Type? PMID- 27380280 TI - Editorial Comment: Advances in PEEK Technology. PMID- 27380279 TI - Hindfoot Arthrodesis with the Blade Plate: Increased Risk of Complications and Nonunion in a Complex Patient Population. AB - BACKGROUND: Previous hindfoot surgeries present a unique challenge to hindfoot arthrodesis, as the patients may have multiple incisions around the hindfoot. In high-risk patients with compromised soft tissues, a posterior approach can provide an alternative for a fresh soft tissue plane for the surgery. The use of a blade plate construct is widely accepted; however, there are limited data supporting the use of a posterior approach. QUESTIONS/PURPOSES: We asked (1) what proportion of patients treated with this technique achieved osseous union; (2) what complications were observed; (3) were any patient-demographic or health related factors associated with the likelihood that a patient would have a complication develop? METHODS: Between December 2001 and July 2014, 42 patients received a posterior blade plate. During the period in question, indications for hindfoot arthrodesis using posterior blade fixation were subtalar osteoarthritis below an ankle fusion, malunion or nonunion, failed tibiotalocalcaneal arthrodesis attributable to nonunion of the tibiotalar and/or subtalar joint; or tibiotalar and subtalar osteoarthritis in patients with impaired bone or soft tissue quality (particularly if the soft tissue problem was anterior). During that period, all patients who met those indications were treated with a posterior blade plate. Forty (95%) were included in this study, and two were lost to followup before the 1-year minimum required by the study. Demographics (age, gender, BMI, smoking status, and comorbidities) and surgical data (indication, previous treatment, and additional procedures) were analyzed. Of the 40 patients included, 27 (68%) were male and 13 (33%) were female, with a median of two previous hindfoot or ankle surgeries (range, 0-9 surgeries). The mean age of the patients was 56 +/- 13 years. Followup averaged 47 +/- 28 months (range, 14-137 months). Twenty-eight of 40 (70%) patients had a tibiotalocalcaneal arthrodesis as a primary (n = 6), primary staged (n = 10), revision (n = 9), or revision staged (n = 3) procedure. Eleven of 40 patients (28%) underwent ankle arthrodesis (primary n = 7, revision n = 4). One of the 40 patients (3%) underwent tibiotalocalcaneal arthrodesis for a failed total ankle arthroplasty. Weightbearing radiographs were used to assess fusion. Osseous fusion was defined as visible trabecular bridging on the lateral and AP ankle views within 6 postoperative months. Delayed union was defined as osseous fusion occurring between 6 and 12 months. Nonunion was defined as no visible trabecular bridging at the latest followup (longer than 12 months). Clinic and surgery notes were reviewed for complications. Univariate analysis was performed to compare patient groups: patients with solid union versus nonunion, and patients with versus without complications. RESULTS: Twenty-nine of 40 (73%) patients had osseous fusion within 6 postoperative months. Four of 40 (10%) patients had a delayed union between 6 and 12 months, and seven of the 40 (18%) patients had nonunions, which occurred in the ankle (n = 3), subtalar (n = 3), or both (n = 1) joints. There were 26 complications observed: 18 (69%) were considered major and eight (31%) were minor. With the numbers available, we did not identify any demographic or surgical factors associated with complications, delayed union, or nonunion. CONCLUSIONS: The proportion of patients treated with a posterior blade plate hindfoot fusion who had delayed union or nonunion is greater than that reported for patients in other series who underwent primary hindfoot arthrodesis with other approaches, and the proportion of patients who had complications develop is high. Further studies are needed to address alternative approaches to achieve hindfoot fusion in patients with complex hindfoot problems. LEVEL OF EVIDENCE: Level IV, therapeutic study. PMID- 27380281 TI - CORR Insights((r)): Reliability and Validity of a Japanese-language and Culturally Adapted Version of the Musculoskeletal Tumor Society Scoring System for the Lower Extremity. PMID- 27380282 TI - The preservation of memory. PMID- 27380284 TI - Quantitative measurement and real-time tracking of high intensity focused ultrasound using phase-sensitive optical coherence tomography: Feasibility study. AB - PURPOSE: Phase-sensitive optical coherence tomography (PhS-OCT) is proposed, as a new high intensity focused ultrasound (HIFU) imaging guidance to detect and track HIFU focus inside 1% agar samples in this work. The experiments studied the effect of varying HIFU power on the induction of shear wave, which can be implemented as a new technique to monitor focused ultrasound surgery (FUS). METHOD: A miniature HIFU transducer (1.02 MHz, 20 mm aperture diameter, 15 mm radius of curvature) was produced in-house, pressure-field mapped, and calibrated. The transducer was then embedded inside a 1% agar phantom, which was placed under PhS-OCT for observation, under various HIFU power settings (acoustic power, and number of cycles per pulse). Shear wave was induced on the sample surface by HIFU and was captured in full under PhS-OCT. The lowest HIFU acoustic power output for the detection of shear wave was found to be 0.36 W (1.02 MHz, 100 cycles/pulse), or with the number of cycles/pulse as low as 20 (1.02 MHz, 0.98 W acoustic power output). RESULTS: A linear relationship between acoustic power output and the maximum shear wave displacement was found in the first study. The second study explores a non-linear correlation between the (HIFU) numbers of cycles per pulse, and the maximum shear wave displacement. CONCLUSION: PhS-OCT demonstrates excellent tracking and detection of HIFU-induced shear wave. The results could benefit other imaging techniques in tracking and guiding HIFU focus. Further studies will explore the relationship between the physical transducer characteristics and the HIFU-induced shear wave. PMID- 27380283 TI - New biofunctional effects of the flower buds of Camellia sinensis and its bioactive acylated oleanane-type triterpene oligoglycosides. AB - We review the biofunctional effects of the flower buds of Camellia sinensis and C. sinensis var. assamica, such as antihyperlipidemic, antihyperglycemic, antiobesity, and gastroprotective effects in vivo, and antiallergic, pancreatic lipase inhibitory, and amyloid beta (Abeta) aggregation inhibitory activities in vitro. Although the biofunctional effects of tea leaves have been extensively studied, less attention has been given to those of the flowers and seeds of the tea plant. Our studies focused on the saponin constituents of the extracts of the flower buds of C. sinensis cultivated in Japan and China, and C. sinensis var. assamica cultivated in India, and we review their beneficial biofunctions for health promotion. PMID- 27380285 TI - [Not Available]. PMID- 27380286 TI - A Windbreaker's Warmth. PMID- 27380287 TI - Brain Anatomy: Thoughts From the Inside. PMID- 27380288 TI - Moderate Alcohol Intake and Cardiometabolic Risk in Adults With Type 2 Diabetes. PMID- 27380289 TI - Moderate Alcohol Intake and Cardiometabolic Risk in Adults With Type 2 Diabetes. PMID- 27380290 TI - Moderate Alcohol Intake and Cardiometabolic Risk in Adults With Type 2 Diabetes. PMID- 27380291 TI - Is Prehospital Advanced Life Support Harmful? PMID- 27380292 TI - Why Physicians Hate "Patient Satisfaction": The Real Reasons. PMID- 27380294 TI - Gout. AB - This issue provides a clinical overview of gout, focusing on prevention and screening, diagnosis, and treatment. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers. PMID- 27380295 TI - Biosynthesis of ZnO nanoparticles using Jacaranda mimosifolia flowers extract: Synergistic antibacterial activity and molecular simulated facet specific adsorption studies. AB - The naturally occurring biomolecules present in the plant extracts have been identified to play an active role in the single step formation of nanoparticles with varied morphologies and sizes which is greener and environmentally benign. In the present work, spherical zinc oxide nanoparticles (ZnO NPs) of 2-4nm size were synthesized using aqueous extract of fallen Jacaranda mimosifolia flowers (JMFs), treated as waste. The microwave assisted synthesis was completed successfully within 5min. Thereafter, phase identification, morphology and optical band gap of the synthesized ZnO NPs were done using X-ray diffraction (XRD), high resolution transmission electron microscopy (HRTEM) and UV-Visible spectroscopy techniques. The composition of JMFs extract was analyzed by gas chromatography-mass spectrometry (GC-MS) and the ZnO NPs confirmation was further explored with fourier transform infrared spectroscopy (FTIR). The GC-MS results confirmed the presence of oleic acid which has high propensity of acting as a reducing and capping agent. The UV-Visible data suggested an optical band gap of 4.03eV for ZnO NPs indicating their small size due to quantum confinement. Further, facet specific adsorption of oleic acid on the surface of ZnO NPs was studied computationally to find out the impact of biomolecules in defining the shape and size of NPs. The viability of gram negative Escherichia coli and gram positive Enterococcus faecium bacteria was found to be 48% and 43%, respectively at high concentration of NPs. PMID- 27380296 TI - Enhanced photocurrent generation in bacteriorhodopsin based bio-sensitized solar cells using gel electrolyte. AB - High purity light sensitive photoactive protein Bacteriorhodopsin (BR) was isolated successfully via a simple two phase extraction technique (ATPS) as an alternate method for the tedious sucrose gradient ultracentrifugation procedure (SGU). Bio sensitized solar cells (BSSCs) were fabricated by the integration of BR into TiO2 (photo anode) with acetamide based gel electrolytes and platinum (photo cathode) as a counter electrode. The structural and photoelectrical behaviours of BR and BSSCs were analyzed by Atomic Force Microscopy, Raman spectroscopy, photocurrent and photovoltage (IV) measurement and electrochemical impedance spectroscopy. The short circuit photocurrent (Jsc) and photoelectric conversion efficiency (eta) of acetamide based gel electrolyte (AG) (1.08mAcm( 2), 0.49%) are twice higher than that of traditional triiodide based liquid electrolyte (LE) (0.62mAcm(-2), 0.19%). Also, quasi-Fermi level and lifetime of photogenerated electrons in acetamide based gel electrolyte is about four times higher than that observed in traditional triiodide redox electrolyte. A comparison of the observed results with similar BSSCs made of other natural photoactive protein systems shows that BR as sensitizer has better photovoltaic performance. The enhanced photocurrent generation of the BSSC constructed in our study could be due to the interaction of BR with acetamide based modified poly(ethylene)oxide (PEO) gel electrolyte. PMID- 27380297 TI - Solvation of the Ca2UO2(CO3)3 Complex in Seawater from Classical Molecular Dynamics. AB - Uranium from the sea provides a long-time supply guarantee of nuclear fuels for centuries to come, and the neutral Ca2UO2(CO3)3 complex has been shown to be the dominant species of uranium in seawater. However, the solvation and structure of the Ca2UO2(CO3)3 complex in seawater have been unclear. Herein we simulate the Ca2UO2(CO3)3 complex in a model seawater solution via classical molecular dynamics. We find that Na(+) and Cl(-) ions interact very differently with the neutral Ca2UO2(CO3)3 complex in seawater. Especially, one Na(+) ion is closely associated with the Ca2UO2(CO3)3 complex, thereby effectively making the complex have a +1 charge, while Cl(-) ions are much farther away. Hence, this work reveals the important role of Na(+) ions in affecting the solvation of the Ca2UO2(CO3)3 complex in seawater, which has implications in designing ligands to attract the Ca2UO2(CO3)3 complex to the sorbent. PMID- 27380299 TI - Join WGO for the Next International Congress in the UAE! Gastro 2016: EGHS-WGO International Congress. PMID- 27380300 TI - Electrochemically Formed Ultrafine Metal Oxide Nanocatalysts for High-Performance Lithium-Oxygen Batteries. AB - Lithium-oxygen (Li-O2) batteries have an extremely high theoretical specific energy density when compared with conventional energy-storage systems. However, practical application of the Li-O2 battery system still faces significant challenges. In this work, we report a new approach for synthesis of ultrafine metal oxide nanocatalysts through an electrochemical prelithiation process. This process reduces the size of NiCo2O4 (NCO) particles from 20-30 nm to a uniformly distributed domain of ~2 nm and significantly improves their catalytic activity. Structurally, the prelithiated NCO nanowires feature ultrafine NiO/CoO nanoparticles that are highly stable during prolonged cycles in terms of morphology and particle size, thus maintaining an excellent catalytic effect to oxygen reduction and evolution reactions. A Li-O2 battery using this catalyst demonstrated an initial capacity of 29 280 mAh g(-1) and retained a capacity of >1000 mAh g(-1) after 100 cycles based on the weight of the NCO active material. Direct in situ transmission electron microscopy observations conclusively revealed the lithiation/delithiation process of as-prepared NCO nanowires and provided in-depth understanding for both catalyst and battery chemistries of transition-metal oxides. This unique electrochemical approach could also be used to form ultrafine nanoparticles of a broad range of materials for catalyst and other applications. PMID- 27380298 TI - Design, synthesis and characterization of linear unnatural amino acids for skin moisturization. AB - OBJECTIVES: This work aimed to design, synthesize and characterize replacement natural moisturizing factor (NMF) composed of modified hygroscopic linear amino acids to pre-empt or repair skin barrier dysfunction. METHODS: Following synthesis and characterization, thermo-gravimetric analysis and quantum mechanics molecular modelling quantified and depicted water binding to the new compounds. Deliquescence relative humidity demonstrated the water-scavenging ability of the compounds, whereas snake skin moisturizing studies showed they increased water uptake into snake skin. RESULTS: From thermal analysis, N-hydroxyglycine showed greatest water-holding capacity followed by N-hydroxyserine, l-homoserine and alpha-hydroxyglycine; coupled with quantum mechanics molecular modelling, between 8 and 12 molecules of water could associate with each molecule of either N hydroxyglycine, N-hydroxyserine or l-homoserine. All of our modified amino acids were efficacious and induced similar or greater water uptake compared with the established moisturizing compounds hyaluronic acid, glycerine and urea in snake skin. Incorporated at 10% in Oilatum, N-hydroxyserine induced >200% greater moisture uptake into dry snake skin compared to treatment with water alone, with efficacy related to the molecule structure and ability to bind to 12 water molecules. Oilatum cream spiked with all our unnatural amino acid hydrotropes increased water uptake into snake skin compared with Oilatum alone. The compound series was designed to elucidate some structure - efficacy relationships. Amino acid chirality did not affect the water-holding capacity but did affect uptake into skin. Compounds with high melting points and bond energies tended to decrease water-holding capacity. With isosteric replacement, the more electronegative atoms gave greater water-holding capacities. CONCLUSIONS: This work demonstrates the potential of unnatural amino acid hydrotropes as skin moisturizers and has developed some predictive 'rules' for further design and refinement of chemical structures. PMID- 27380301 TI - Synthesis, energy transfer and tunable emission properties of SrSb2O6:Eu(3+), Bi(3+) phosphor. AB - Host SrSb2O6, SrSb2O6:Bi(3+), SrSb2O6:Eu(3+), and SrSb2O6:Eu(3+), Bi(3+) phosphors are synthesized by solid state reaction method in air. Host SrSb2O6 with excitation 254nm shows weak green-yellow emission in the range of 320-780nm due to Sb(5+)->O(2-) transition. SrSb2O6:Bi(3+) phosphor with excitation 365nm emits green light within the range 400-650nm owing to the (3)P1->(1)S0 transition of Bi(3+) ion. SrSb2O6:Eu(3+) phosphor with excitation 254nm exhibits a systematically varied hue from green to orange-red light by increasing Eu(3+) concentration from 0 to 7mol%, and that with excitation 394nm only shows orange red light. The optimal Eu(3+) concentration is ~4mol% in SrSb2O6:Eu(3+) phosphor. SrSb2O6:Eu(3+), Bi(3+) phosphor with excitation 254 and 394nm emits orange-red light. Emission intensity of SrSb2O6:Eu(3+) phosphor may be enhanced >2 times by co-doping Bi(3+) ion because of the fluxing agent and energy transfer roles of Bi(3+) ion in SrSb2O6:Eu(3+), Bi(3+) phosphor. The luminous mechanism of SrSb2O6:Eu(3+), Bi(3+) phosphor is analyzed and explained by the simplified energy level diagrams of Sb2O6(2-) group, Bi(3+) and Eu(3+) ions, and energy transfer processes between them. PMID- 27380302 TI - Linear model correction: A method for transferring a near-infrared multivariate calibration model without standard samples. AB - Calibration transfer is essential for practical applications of near infrared (NIR) spectroscopy because the measurements of the spectra may be performed on different instruments and the difference between the instruments must be corrected. For most of calibration transfer methods, standard samples are necessary to construct the transfer model using the spectra of the samples measured on two instruments, named as master and slave instrument, respectively. In this work, a method named as linear model correction (LMC) is proposed for calibration transfer without standard samples. The method is based on the fact that, for the samples with similar physical and chemical properties, the spectra measured on different instruments are linearly correlated. The fact makes the coefficients of the linear models constructed by the spectra measured on different instruments are similar in profile. Therefore, by using the constrained optimization method, the coefficients of the master model can be transferred into that of the slave model with a few spectra measured on slave instrument. Two NIR datasets of corn and plant leaf samples measured with different instruments are used to test the performance of the method. The results show that, for both the datasets, the spectra can be correctly predicted using the transferred partial least squares (PLS) models. Because standard samples are not necessary in the method, it may be more useful in practical uses. PMID- 27380303 TI - Spectroscopic evidence on improvement in complex formation of O2N2 aza-crown macrocyclic ligands with Cu(II) acetate upon incorporation with [60]Fullerene. AB - The present paper reports the spectroscopic investigations on the complexation of Cu(II) with two macrocyclic ligands bonded to [60]Fullerene (L1 and L2) measured in N-methylpyrrolidone (NMP) as solvent. On the basis of UV-vis-NIR spectroscopy applying Jobs method of continuous variation, typical 1:1 stoichiometries were established for the complexes of Cu(II) with L1, and L2. DFT calculations suggested that superior HOMO distributions spread over the nitrogen-donor (as well as somehow oxygen- donor in L2) groups of L1 and L2 macrocycles were the key factor for the observed Kb value enhancement. Thermodynamic stabilities for these complexes have also been determined employing Benesi-Hildebrand equation and the results were compared in terms of their calculated binding constants (Kb). These measurements showed that L1 and L2 bound to these cations stronger than their parent free macrocyclic ligands 1 and 2, respectively. Furthermore, Kb values found for L2 complexes revealed that it could coordinate Cu(II) cation better than L1. Thermodynamic parameters (DeltaG, ?H, and -DeltaS) derived from Van't Hoff equation showed that L1 and L2 coordination of Cu(II) cation were occurred due to both enthalpic and entropic factors while the coordination of Cu(II) with their parent macrocyclic ligands 1 and 2 only enjoyed from only enthalpic advantages. PMID- 27380304 TI - Determination of trace uranium by resonance fluorescence method coupled with photo-catalytic technology and dual cloud point extraction. AB - In this paper, two kinds of salophens (Sal) with different solubilities, Sal1 and Sal2, have been respectively synthesized, and they all can combine with uranyl to form stable complexes: [UO2(2+)-Sal1] and [UO2(2+)-Sal2]. Among them, [UO2(2+) Sal1] was used as ligand to extract uranium in complex samples by dual cloud point extraction (dCPE), and [UO2(2+)-Sal2] was used as catalyst for the determination of uranium by photocatalytic resonance fluorescence (RF) method. The photocatalytic characteristic of [UO2(2+)-Sal2] on the oxidized pyronine Y (PRY) by potassium bromate which leads to the decrease of RF intensity of PRY were studied. The reduced value of RF intensity of reaction system (DeltaF) is in proportional to the concentration of uranium (c), and a novel photo-catalytic RF method was developed for the determination of trace uranium (VI) after dCPE. The combination of photo-catalytic RF techniques and dCPE procedure endows the presented methods with enhanced sensitivity and selectivity. Under optimal conditions, the linear calibration curves range for 0.067 to 6.57ngmL(-1), the linear regression equation was DeltaF=438.0 c (ngmL(-1))+175.6 with the correlation coefficient r=0.9981. The limit of detection was 0.066ngmL(-1). The proposed method was successfully applied for the separation and determination of uranium in real samples with the recoveries of 95.0-103.5%. The mechanisms of the indicator reaction and dCPE are discussed. PMID- 27380305 TI - Detection of Citrus tristeza virus by using fluorescence resonance energy transfer-based biosensor. AB - Due to the low titer or uneven distribution of Citrus tristeza virus (CTV) in field samples, detection of CTV by using conventional detection techniques may be difficult. Therefore, in the present work, the cadmium-telluride quantum dots (QDs) was conjugated with a specific antibody against coat protein (CP) of CTV, and the CP were immobilized on the surface of gold nanoparticles (AuNPs) to develop a specific and sensitive fluorescence resonance energy transfer (FRET) based nanobiosensor for detecting CTV. The maximum FRET efficiency for the developed nano-biosensor was observed at 60% in AuNPs-CP/QDs-Ab ratio of 1:8.5. The designed system showed higher sensitivity and specificity over enzyme linked immunosorbent assay (ELISA) with a limit of detection of 0.13MUgmL(-1) and 93% and 94% sensitivity and specificity, respectively. As designed sensor is rapid, sensitive, specific and efficient in detecting CTV, this could be envisioned for diagnostic applications, surveillance and plant certification program. PMID- 27380306 TI - Development of a reliable analytical method for the precise extractive spectrophotometric determination of osmium(VIII) with 2 nitrobenzaldehydethiocarbohydrazone: Analysis of alloys and real sample. AB - The proposed method demonstrates that the osmium(VIII) forms complex with 2 NBATCH from 0.8molL(-1) HCl at room temperature. The complex formed was extracted in 10mL of chloroform with a 5min equilibration time. The absorbance of the red colored complex was measured at 440nm against the reagent blank. The Beer's law was obeyed in the range of 5-25MUgmL(-1), the optimum concentration range was 10 20MUgmL(-1) of osmium(VIII) as evaluated by Ringbom's plot. Molar absorptivity and Sandell's sensitivity of osmium(VIII)-2NBATCH complex in chloroform is 8.94*10(3)Lmol(-1)cm(-1) and 0.021MUgcm(-2), respectively. The composition of osmium(VIII)-2NBATCH complex was 1:2 investigated from Job's method of continuous variation, Mole ratio method and slope ratio method. The interference of diverse ions was studied and masking agents were used wherever necessary. The present method was successfully applied for determination of osmium(VIII) from binary, ternary and synthetic mixtures corresponding to alloys and real samples. The validity of the method was confirmed by finding the relative standard deviation for five determinations which was 0.29%. PMID- 27380307 TI - Fully parametric imaging with reversible tracer 18F-FLT within a reasonable time. AB - PET enables quantitative imaging of the rate constants K 1, k 2, k 3, and k 4, with a reversible two tissue compartment model (2TCM). A new method is proposed for computing all of these rates within a reasonable time, less than 1 min. A set of differential equations for the reversible 2TCM was converted into a single formula consisting of differential and convolution terms. The validity was tested on clinical data with 18F-FLT PET for patients with glioma (n = 39). Parametric images were generated with the formula that was developed. Parametric values were extracted from regions of interest (ROIs) for glioma from the images generated, and they were compared with those obtained with the non-linear fitting method. We performed simulation studies for testing accuracy by generating simulated images, assuming clinically expected ranges of the parametric values. The computation time was about 20 s, and the quality of the images generated was acceptable. The values obtained for K 1 for grade IV tumor were 0.24 +/- 0.23 and 0.26 +/- 0.25 ml-1 min-1 g-1 for the image-based and ROI-based methods, respectively. The values were 0.21 +/- 0.12 and 0.21 +/- 0.12 min-1 for k 2, 0.13 +/- 0.07 and 0.13 +/- 0.07 min-1 for k 3, and 0.052 +/- 0.020 and 0.054 +/- 0.021 min-1 for k 4. The differences between the methods were not significant. Regression analysis showed correlations of r = 0.94, 0.86, 0.71, and 0.52 for these parameters. Simulation demonstrated that the accuracy was within acceptable ranges, namely, the correlations were r = 0.99, r = 0.97, r = 0.99, and r = 0.91 for K 1, k 2, k 3, and k 4, respectively, between estimated and assumed values. This results suggest that parametric images can be obtained fully within reasonable time, accuracy, and quality. PMID- 27380308 TI - Specific Detection of Dog Podoplanin Expressed in Renal Glomerulus by a Novel Monoclonal Antibody PMab-38 in Immunohistochemistry. AB - Podoplanin (PDPN) is expressed in several normal tissues including podocytes of renal glomerulus, lymphatic endothelial cells (LECs), and type I alveolar cells of lung. PDPN activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelets. Many monoclonal antibodies (mAbs) against human PDPN, mouse PDPN, rat PDPN, rabbit PDPN, and bovine PDPN have been established; antidog PDPN (dPDPN) mAbs have not been developed. Herein, we immunized mice with the recombinant proteins of dPDPN and developed anti-dPDPN mAbs. One of the clones, PMab-38, is useful for detecting podocytes in immunohistochemical analysis; in contrast, it did not react with LECs or type I alveolar cells. PMab 38 also detected dPDPN specifically in flow cytometry and Western blot analysis. PMab-38 is expected to be useful for investigating the function of dPDPN, which is expressed in podocytes. PMID- 27380310 TI - The role of amino acid profiles in diabetes risk assessment. AB - PURPOSE OF REVIEW: The concentrations of plasma-free amino acids, such as branched-chain amino acids and aromatic amino acids, are associated with visceral obesity, insulin resistance, and the future development of diabetes and cardiovascular diseases. This review discusses recent progress in the early assessment of the risk of developing diabetes and the reversal of altered plasma free amino acids through interventions. Additionally, recent developments that have increased the utility of amino acid profiling technology are also described. RECENT FINDINGS: Plasma-free amino acid alterations in the early stage of lifestyle-related diseases are because of obesity and insulin resistance-related inflammation, and these alterations are reversed by appropriate (nutritional, drug, or surgical) interventions that improve insulin sensitivity. For clinical applications, procedures for measuring amino acids are being standardized and automated. SUMMARY: Plasma-free amino acid profiles have potential as biomarkers for both assessing diabetes risk and monitoring the effects of strategies designed to lower that risk. In addition, the methodology for measuring amino acids has been refined, with the goal of routine clinical application. PMID- 27380309 TI - Differential selection of sodium and potassium ions by TsHKT1;2. AB - Among abiotic stresses, soil salinity is a major threat to agriculture. To address and control the effects of high salinity on plants, it is important to understand their responses to salt stress that disturbs the homeostatic equilibrium at cellular and molecular levels. To deal and control effects of high salinity on plants, it is important to understand their responses to salt stress that disturbs the homeostatic equilibrium at cellular and molecular levels. In this regard, halophytes (salt tolerant plants) can provide superior models for the study of salt stress defense parameters compared to glycophytes (salt sensitive species). TsHKT1;2 one of the 3 copies of HKT1 in the Arabidopsis relative halophyte, Thellungiella salsuginea acts as a potassium transporter, even under salt stress. TsHKT1;2 includes a conserved Asp (D) residue in the 2(nd) pore-loop domain. Most other HKT1 sequences, including AtHKT1, contain Asn (N) in this position. We found that athkt1-1 plants complemented by TsHKT1;2 under native AtHKT1 promoter were more tolerant to salt stress, while substitution of Asp (D207) by Asn (N) significantly reduced resistance to salinity. We suggest that the presence of Asn or Asp is the essential feature that defines and establishes cation selectivity in dicot HKT1-type transporters. PMID- 27380311 TI - Hepatic steatosis: a role for citrulline. AB - PURPOSE OF REVIEW: The high worldwide prevalence of nonalcoholic fatty liver disease (NAFLD) makes it a major public health issue. Amino acids offer a promising approach for its prevention, and several experimental studies highlight the nutritional importance of citrulline in this setting. The purpose of this review is to discuss the potential interest of citrulline in the prevention and treatment of NAFLD. RECENT FINDINGS: Current findings shed light on the role of the gut-liver, adipose tissue-liver, and muscle-liver axes in NAFLD progression. Recent experimental studies have produced evidence for a role of citrulline in controlling the pathophysiological mechanisms involved in NAFLD through its action on these three axes. Data are needed to distinguish between direct and indirect effects of citrulline on the liver and between a specific effect and a nitrogen supply-related effect. SUMMARY: Good level of experimental evidence suggests that citrulline supply may be associated with an attenuation of NAFLD development, but further human studies are now needed to support these findings. This review may help define novel strategies to control fatty liver diseases. PMID- 27380312 TI - Quality of meal and appetite sensation. AB - PURPOSE OF REVIEW: The scope of this review is to summarize recent studies assessing the role of meal composition on appetite sensation. RECENT FINDINGS: Currently, data confirm a positive effect on appetite sensations following protein-rich meals, suggesting that at least 25-30-g protein/meal provide potential improvements on appetite, but further long-term studies are required to confirm the results. A greater interest has been showed in the interaction between short-chain fatty acids produced by gut microbiota, following dietary fiber consumption, and appetite sensation, but research is ongoing. Finally, as reflected in the recent literature, new systematic reviews should be carried out to assess the effect of dietary fibers on appetite sensation. SUMMARY: Meal composition, in terms of nutrients, widely differs in the ability to affect appetite sensation. This mostly depends on the content of protein and dietary fibers in a meal. The effect of higher protein intake on appetite sensation has been well documented with positive results, whereas dietary fibers, although the majority of evidence suggests positive results, still show inconsistent data because of various methodological approaches. Generally, more research both in the short and long term is required to investigate the underlying mechanism associated with appetite sensation. PMID- 27380313 TI - Combined Photoredox and Lewis Acid Catalyzed alpha-Hydroxyalkylation of Cyclic Ethers with Aromatic Ketones. AB - The photochemically induced coupling of aromatic ketones with cyclic ethers such as tetrahydrofuran, tetrahydropyran, and 1,4-dioxane was studied. Direct photolysis of the substrates with UV-A light centered at 350 nm does not lead to photoinduced hydrogen transfer whereas the addition of a mixture of the Lewis acid catalysts Ti(O(i)Pr)4 and BF3 enables the formation of the hydroxyalkylation products. PMID- 27380314 TI - Paraoxonase-2 and paraoxonase-3: comparison of mRNA expressions in the placentae of unexplained intrauterine growth restricted and noncomplicated pregnancies. AB - OBJECTIVE: Recent evidence suggests that oxidative stress is involved in the pathophysiology of many human diseases. It has been demonstrated that oxidative stress is associated with intrauterine growth restriction (IUGR), and the depletion of placental antioxidant systems has been suggested as a key factor in this disease. Our aims were to explore the possible role of antioxidant paraoxonase-2 (PON2) and paraoxonase-3 (PON3) in the pathophysiology of unexplained IUGR. METHODS: We have studied the expression of mRNA for PON2, PON3 in placental tissues by using RT-qPCR. Two groups, consisting of normal (n = 18) and unexplained IUGR pregnancies (n = 20) were compared. RESULTS: Our results demonstrated that there were no significant differences in the mRNA expressions of PON2, PON3 between the two groups (p = 0.28, p = 0.90, respectively). PON2 and PON3 were down-regulated in IUGR. Antenatal steroid therapy had no effect on the expression mRNA in placentae of unexplained IUGR pregnancies compared to non treated group. CONCLUSIONS: These results suggest that PON2, PON3 mRNA levels were not changed significantly in placentae of IUGR when compared to normal pregnant women. PMID- 27380315 TI - Mutation of Rice Early Flowering3.1 (OsELF3.1) delays leaf senescence in rice. AB - In Arabidopsis, EARLY FLOWERING3 (ELF3) has pivotal roles in controlling circadian rhythm and photoperiodic flowering. In addition, ELF3 negatively regulates leaf senescence by repressing the transcription of PHYTOCHROME INTERACTING FACTOR4 (PIF4) and PHYTOCHROME-INTERACTING FACTOR5 (PIF5); elf3 mutants senesce earlier and ELF3-overexpressing (ELF3-OX) plants senesce later than wild type (WT). Here, we show that in contrast to Arabidopsis ELF3, which represses senescence, the rice homolog OsELF3.1 promotes leaf senescence; oself3.1 mutants showed delayed senescence and OsELF3.1-OX plants senesced earlier under both dark-induced and natural senescence conditions. Microarray analysis revealed that in the senescing leaves, a number of senescence-associated genes, phytohormone-related genes, and NAC and WRKY family genes (OsNAP, ONAC106, and OsWRKY42) were differentially expressed in oself3.1 mutants compared with WT. Interestingly, we found that Arabidopsis plants overexpressing OsELF3.1 show delayed leaf senescence, produce short petioles, and flower late in long days, just like Arabidopsis ELF3-OX plants. This demonstrates that the regulatory functions of ELF3 and OsELF3.1 are conserved between Arabidopsis and rice, but the downstream regulatory cascades have opposite effects. PMID- 27380316 TI - Using Surface Scans for the Evaluation of Halogen Bonds toward the Side Chains of Aspartate, Asparagine, Glutamate, and Glutamine. AB - Using halogen-specific Connolly type molecular surfaces, we herein invented a new type of surface-based interaction analysis employed for the study of halogen bonding toward model systems of biologically relevant carboxylates (ASP/GLU) and carboxamides (ASN/GLN). Database mining and statistical assessment of the PDB revealed that such interactions are widely underrepresented at the moment. We observed important distance-dependent adaptions of the binding modes of halobenzenes from a preferential oxygen-directed to a bifurcated interaction geometry of the carboxylate. In addition, halogen...pi contacts perpendicular to the nitrogen atom of the carboxamide become increasingly important for the lighter halogens. Our analysis on a MP2/TZVPP level of theory is backed by CCSD(T)/CBS reference calculations. To put the vast interaction energies into perspective, we also performed COSMO-RS calculations of the solvation free energy. Facilitating the visualization of our results mapped onto any binding site of choice, we aim to inspire more design studies showcasing these underrepresented interactions. PMID- 27380317 TI - Efficacy of a specific polyclonal equine F(ab')2 against avian influenza (H5N1) in ferrets: synergy with oseltamivir. AB - AIM: Current therapies against avian influenza (H5N1) provide limited clinical benefit. FBF-001 is a highly purified equine polyclonal immunoglobulin fragment against H5N1. METHODS: Using a ferret model of severe acute H5N1 infection, we assessed FBF-001 when administered on the same day or 1 day after viral challenge, in comparison with oseltamivir therapy. RESULTS: Untreated animals died 2-3 days after challenge. FBF-001 prevented most severe illness and reduced nasal viral load, with best efficacy when administered on the day of viral challenge. Oseltamivir and FBF-001 had synergistic impact on survival. CONCLUSION: FBF-001 prevented severe consequences of lethal H5N1 challenge in ferrets by controlling viral replication, an effect synergistic to oseltamivir. FBF-001 has recently been granted EMA orphan drug status. PMID- 27380318 TI - Focal Adhesion Kinase Directly Interacts with TSC2 Through Its FAT Domain and Regulates Cell Proliferation in Cashmere Goat Fetal Fibroblasts. AB - Focal adhesion kinase (FAK) is a cytoplasmic nonreceptor tyrosine kinase that senses a variety of extracellular signals, such as growth factors and integrins, to control the process of cell proliferation and metabolism. We cloned three goat FAK transcript variants (KM655805, KM658268, and KM658269) that encode 1052, 1006, and 962 amino-acid residue proteins. Bioinformatics analysis indicated that the putative FAK protein contains an FERM domain, a PTK domain, two Proline-rich regions, and a focal adhesion-targeting (FAT) domain. All the three transcript variants of FAK were detected in seven different goat tissues, and variant 1 had the most accumulation whereas variant 2 and variant 3 had lower accumulation. Treatment of goat fetal fibroblasts (GFbs) with a specific FAK inhibitor, TAE226, inhibited cell proliferation (p < 0.05) and induced damage to the cell morphology in a dose- and time-dependent manner. Further research demonstrated that FAK directly interacted with TSC2 (Tuberous sclerosis 2) tuberin domain through its C terminus, which contains the complete FAT domain. In conclusion, our results indicated that FAK may be widely expressed in Cashmere goat tissues and its products participate in the mammalian target of rapamycin signaling pathway and cell proliferation through a direct interaction with TSC2 in GFBs. PMID- 27380319 TI - Imaging characteristics of cervical spine extra-arachnoid fluid collections managed conservatively. AB - OBJECTIVE: Determine the MRI characteristics of large post-traumatic cervical spine extra-arachnoid collections managed conservatively in clinically stable patients and whether evidence of clinical or imaging deterioration materialized. MATERIALS AND METHODS: Following IRB approval, we conducted a retrospective search for all patients (>16 years old) over a 17-months period who had an extra arachnoid fluid collection reported on a post-traumatic cervical spine MRI. Patients were excluded if they had surgery for an unstable fracture (n = 21), emergent decompression (n = 1) or lacked a follow-up MRI within 15 days (n = 1). Two MSK radiologists recorded the size, morphology and MRI signal characteristics of the collections. RESULTS: Eight patients (5 male, 3 female) met the inclusion criteria (mean age 40 years; range 19-78 years). Seven of the eight patients had fluid collections that demonstrated thin, tapered margins, extended >7 vertebral bodies and involved >180 degrees of the spinal canal. The signal characteristics of these collections varied: hyper-T1/iso-T2 (n = 1), iso-T1/T2 (n = 3), hyper T1/hypo-T2 (n = 3) and mixed-T1/T2 (n = 1). Six of seven collections were ventral. Follow-up MRI demonstrated resolution/significant decrease in size (n = 4 between 1 and 12 days) or no change/slight decrease in size (n = 3; between 2 and 11 days). None of the seven fluid collections enlarged, no patient had abnormal cord signal, and no patient's neurologic symptoms worsened. One of eight patients had a dorsal "mass-like" collection that was slightly smaller 9 days later. CONCLUSION: In stable patients with large, tapered post-traumatic cervical spine extra-arachnoid collections managed non-surgically, none developed (1) clinical worsening, (2) abnormal cord signal or (3) collection enlargement, regardless of the collection's signal characteristics. PMID- 27380320 TI - Core-Shell Particles for Simultaneous 3D Imaging and Optical Tweezing in Dense Colloidal Materials. AB - A new colloidal system that consists of core-shell "probe" particles embedded in an optically transparent "host" particle suspension is developed. This system enables simultaneous fast confocal imaging and optical tweezing in dense 3D colloidal materials. PMID- 27380322 TI - CFD transient simulation of the cough clearance process using an Eulerian wall film model. AB - In this study, a cough cycle is reproduced using a computational methodology. The Eulerian wall film approach is proposed to simulate airway mucus flow during a cough. The reproduced airway domain is based on realistic geometry from the literature and captures the deformation of flexible tissue. To quantify the overall performance of this complex phenomenon, cough efficiency (CE) was calculated, which provided an easily reproducible measurement parameter for the cough clearance process. Moreover, the effect of mucus layer thickness was examined. The relationship between the CE and the mucus viscosity was quantified using reductions from 20 to 80%. Finally, predictions of CE values based on healthy person inputs were compared with values obtained from patients with different respiratory diseases, including chronic obstructive pulmonary disease (COPD) and respiratory muscle weakness (RMW). It was observed that CE was reduced by 50% in patients with COPD compared with that of a healthy person. On average, CE was reduced in patients with RMW to 10% of the average value of a healthy person. PMID- 27380321 TI - ZDHHC7-mediated S-palmitoylation of Scribble regulates cell polarity. AB - Scribble (SCRIB) is a tumor-suppressor protein, playing critical roles in establishing and maintaining epithelial cell polarity. SCRIB is frequently amplified in human cancers but does not localize properly to cell-cell junctions, suggesting that mislocalization of SCRIB disrupts its tumor-suppressive activities. Using chemical reporters, here we showed that SCRIB localization was regulated by S-palmitoylation at conserved cysteine residues. Palmitoylation deficient mutants of SCRIB were mislocalized, leading to disruption of cell polarity and loss of their tumor-suppressive activities to oncogenic YAP, MAPK and PI3K/AKT pathways. We further found that ZDHHC7 was the major palmitoyl acyltransferase regulating SCRIB. Knockout of ZDHHC7 led to SCRIB mislocalization and YAP activation, and disruption of SCRIB's suppressive activities in HRas(V12) induced cell invasion. In summary, we demonstrated that ZDHHC7-mediated SCRIB palmitoylation is critical for SCRIB membrane targeting, cell polarity and tumor suppression, providing new mechanistic insights of how dynamic protein palmitoylation regulates cell polarity and tumorigenesis. PMID- 27380324 TI - [Intraoperative OCT technology : Nice pictures or more?]. PMID- 27380323 TI - Infant Protection Against Influenza Through Maternal Immunization: A Call for More Immunogenic Vaccines. PMID- 27380325 TI - [Revision procedures after canaloplasty]. AB - Canaloplasty is a recently introduced non-penetrating surgical technique for glaucoma, which seeks to improve the natural outflow of aqueous humor through Schlemm's canal and the collector channels. Just as in all forms of glaucoma surgery there are a certain number of failures of the procedure and further surgery is often needed to reduce the intraocular pressure in these cases. This article describes some of the revision procedures after canaloplasty. PMID- 27380326 TI - [Mastered with statistics: perfect eye drops and ideal screening test : Possibilities and limits of statistical methods for glaucoma]. AB - BACKGROUND: The use and the understanding of statistics are very important for biomedical research and for the clinical practice. This is particularly true for estimation of the possibilities for different diagnostic and therapy options in the field of glaucoma. The apparent complexity and contraintuitiveness of statistics along with a cautious acceptance by many physicians, might be the cause of conscious and unconscious manipulation with data representation and interpretation. OBJECTIVES: Comprehendable clarification of some typical errors in the handling of medical statistical data. MATERIALS AND METHODS: Using two hypothetical examples from glaucoma diagnostics the presentation of the effect of a hypotensive drug and interpretation of the results of a diagnostic test and typical statistical applications and sources of error are analyzed in detail and discussed. RESULTS: Mechanisms of data manipulation and incorrect data interpretation are elucidated. Typical sources of error in the statistical analysis and data presentation are explained. CONCLUSION: The practical examples analyzed demonstrate the need to understand the basics of statistics and to be able to apply them correctly. The lack of basic knowledge or half-knowledge in medical statistics can lead to misunderstandings, confusion and wrong decisions in medical research and also in clinical practice. PMID- 27380338 TI - A PIECE OF MY MIND. "Vote for Me". PMID- 27380341 TI - Lynch Syndrome Testing: A Missed Opportunity in the Era of Precision Medicine. PMID- 27380329 TI - Frog Pond: Larry Bell. PMID- 27380330 TI - Changing Physician Behavior Is Harder Than We Thought. PMID- 27380337 TI - Health Insurance Stores and Health Hubs: Innovations That Get Close to the Customer. PMID- 27380339 TI - Deutetrabenazine for Treatment of Chorea in Huntington Disease. PMID- 27380340 TI - Strategies to Support Surrogate Decision Makers of Patients With Chronic Critical Illness: The Search Continues. PMID- 27380344 TI - Association of a Genetic Risk Score With Body Mass Index Across Different Birth Cohorts. AB - IMPORTANCE: Many genetic variants are associated with body mass index (BMI). Associations may have changed with the 20th century obesity epidemic and may differ for black vs white individuals. OBJECTIVE: Using birth cohort as an indicator for exposure to obesogenic environment, to evaluate whether genetic predisposition to higher BMI has a larger magnitude of association among adults from more recent birth cohorts, who were exposed to the obesity epidemic at younger ages. DESIGN, SETTING, AND PARTICIPANTS: Observational study of 8788 adults in the US national Health and Retirement Study who were aged 50 years and older, born between 1900 and 1958, with as many as 12 BMI assessments from 1992 to 2014. EXPOSURES: A multilocus genetic risk score for BMI (GRS-BMI), calculated as the weighted sum of alleles of 29 single nucleotide polymorphisms associated with BMI, with weights equal to the published per-allele effects. The GRS-BMI represents how much each person's BMI is expected to differ, based on genetic background (with respect to these 29 loci), from the BMI of a sample member with median genetic risk. The median-centered GRS-BMI ranged from -1.68 to 2.01. MAIN OUTCOMES AND MEASURES: BMI based on self-reported height and weight. RESULTS: GRS BMI was significantly associated with BMI among white participants (n = 7482; mean age at first assessment, 59 years; 3373 [45%] were men; P <.001) and among black participants (n = 1306; mean age at first assessment, 57 years; 505 [39%] were men; P <.001) but accounted for 0.99% of variation in BMI among white participants and 1.37% among black participants. In multilevel models accounting for age, the magnitude of associations of GRS-BMI with BMI were larger for more recent birth cohorts. For example, among white participants, each unit higher GRS BMI was associated with a difference in BMI of 1.37 (95% CI, 0.93 to 1.80) if born after 1943, and 0.17 (95% CI, -0.55 to 0.89) if born before 1924 (P = .006). For black participants, each unit higher GRS-BMI was associated with a difference in BMI of 3.70 (95% CI, 2.42 to 4.97) if born after 1943, and 1.44 (95% CI, -1.40 to 4.29) if born before 1924. CONCLUSIONS AND RELEVANCE: For participants born between 1900 and 1958, the magnitude of association between BMI and a genetic risk score for BMI was larger among persons born in later cohorts. This suggests that associations of known genetic variants with BMI may be modified by obesogenic environments. PMID- 27380345 TI - Attitudes and Practices of Euthanasia and Physician-Assisted Suicide in the United States, Canada, and Europe. AB - IMPORTANCE: The increasing legalization of euthanasia and physician-assisted suicide worldwide makes it important to understand related attitudes and practices. OBJECTIVE: To review the legal status of euthanasia and physician assisted suicide and the available data on attitudes and practices. EVIDENCE REVIEW: Polling data and published surveys of the public and physicians, official state and country databases, interview studies with physicians, and death certificate studies (the Netherlands and Belgium) were reviewed for the period 1947 to 2016. FINDINGS: Currently, euthanasia or physician-assisted suicide can be legally practiced in the Netherlands, Belgium, Luxembourg, Colombia, and Canada (Quebec since 2014, nationally as of June 2016). Physician-assisted suicide, excluding euthanasia, is legal in 5 US states (Oregon, Washington, Montana, Vermont, and California) and Switzerland. Public support for euthanasia and physician-assisted suicide in the United States has plateaued since the 1990s (range, 47%-69%). In Western Europe, an increasing and strong public support for euthanasia and physician-assisted suicide has been reported; in Central and Eastern Europe, support is decreasing. In the United States, less than 20% of physicians report having received requests for euthanasia or physician-assisted suicide, and 5% or less have complied. In Oregon and Washington state, less than 1% of licensed physicians write prescriptions for physician-assisted suicide per year. In the Netherlands and Belgium, about half or more of physicians reported ever having received a request; 60% of Dutch physicians have ever granted such requests. Between 0.3% to 4.6% of all deaths are reported as euthanasia or physician-assisted suicide in jurisdictions where they are legal. The frequency of these deaths increased after legalization. More than 70% of cases involved patients with cancer. Typical patients are older, white, and well-educated. Pain is mostly not reported as the primary motivation. A large portion of patients receiving physician-assisted suicide in Oregon and Washington reported being enrolled in hospice or palliative care, as did patients in Belgium. In no jurisdiction was there evidence that vulnerable patients have been receiving euthanasia or physician-assisted suicide at rates higher than those in the general population. CONCLUSIONS AND RELEVANCE: Euthanasia and physician-assisted suicide are increasingly being legalized, remain relatively rare, and primarily involve patients with cancer. Existing data do not indicate widespread abuse of these practices. PMID- 27380343 TI - Effect of Palliative Care-Led Meetings for Families of Patients With Chronic Critical Illness: A Randomized Clinical Trial. AB - IMPORTANCE: Family caregivers of patients with chronic critical illness experience significant psychological distress. OBJECTIVE: To determine whether family informational and emotional support meetings led by palliative care clinicians improve family anxiety and depression. DESIGN, SETTING, AND PARTICIPANTS: A multicenter randomized clinical trial conducted from October 2010 through November 2014 in 4 medical intensive care units (ICUs). Adult patients (aged >=21 years) requiring 7 days of mechanical ventilation were randomized and their family surrogate decision makers were enrolled in the study. Observers were blinded to group allocation for the measurement of the primary outcomes. INTERVENTIONS: At least 2 structured family meetings led by palliative care specialists and provision of an informational brochure (intervention) compared with provision of an informational brochure and routine family meetings conducted by ICU teams (control). There were 130 patients with 184 family surrogate decision makers in the intervention group and 126 patients with 181 family surrogate decision makers in the control group. MAIN OUTCOMES AND MEASURES: The primary outcome was Hospital Anxiety and Depression Scale symptom score (HADS; score range, 0 [best] to 42 [worst]; minimal clinically important difference, 1.5) obtained during 3-month follow-up interviews with the surrogate decision makers. Secondary outcomes included posttraumatic stress disorder experienced by the family and measured by the Impact of Events Scale-Revised (IES-R; total score range, 0 [best] to 88 [worst]), discussion of patient preferences, hospital length of stay, and 90-day survival. RESULTS: Among 365 family surrogate decision makers (mean age, 51 years; 71% female), 312 completed the study. At 3 months, there was no significant difference in anxiety and depression symptoms between surrogate decision makers in the intervention group and the control group (adjusted mean HADS score, 12.2 vs 11.4, respectively; between-group difference, 0.8 [95% CI, -0.9 to 2.6]; P = .34). Posttraumatic stress disorder symptoms were higher in the intervention group (adjusted mean IES-R score, 25.9) compared with the control group (adjusted mean IES-R score, 21.3) (between-group difference, 4.60 [95% CI, 0.01 to 9.10]; P = .0495). There was no difference between groups regarding the discussion of patient preferences (intervention, 75%; control, 83%; odds ratio, 0.63 [95% CI, 0.34 to 1.16; P = .14]). The median number of hospital days for patients in the intervention vs the control group (19 days vs 23 days, respectively; between-group difference, -4 days [95% CI, -6 to 3 days]; P = .51) and 90-day survival (hazard ratio, 0.95 [95% CI, 0.65 to 1.38], P = .96) were not significantly different. CONCLUSIONS AND RELEVANCE: Among families of patients with chronic critical illness, the use of palliative care-led informational and emotional support meetings compared with usual care did not reduce anxiety or depression symptoms and may have increased posttraumatic stress disorder symptoms. These findings do not support routine or mandatory palliative care-led discussion of goals of care for all families of patients with chronic critical illness. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01230099. PMID- 27380342 TI - Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease: A Randomized Clinical Trial. AB - IMPORTANCE: Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. OBJECTIVE: To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. DESIGN, SETTING, AND PARTICIPANTS: Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. INTERVENTIONS: Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. MAIN OUTCOMES AND MEASURES: Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form- physical functioning subscale score (SF-36), and the change in the Berg Balance Test. RESULTS: Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2 12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was -2.5 units (95% CI, -3.7 to -1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3 50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, -0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. CONCLUSIONS AND RELEVANCE: Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01795859. PMID- 27380347 TI - Tumor Screening and DNA Testing in the Diagnosis of Lynch Syndrome. PMID- 27380346 TI - Arthralgia and Fevers in a Patient With Autoimmune Hepatitis. PMID- 27380349 TI - Human Granulocytic Anaplasmosis and Lyme Disease. PMID- 27380348 TI - Association Between Gadolinium Contrast Exposure and the Risk of Parkinsonism. PMID- 27380350 TI - Acetazolamide and Invasive Mechanical Ventilation for Patients With COPD. PMID- 27380351 TI - Human Granulocytic Anaplasmosis and Lyme Disease--Reply. PMID- 27380352 TI - Acetazolamide and Invasive Mechanical Ventilation for Patients With COPD. PMID- 27380353 TI - Acetazolamide and Invasive Mechanical Ventilation for Patients With COPD--Reply. PMID- 27380354 TI - Task-Oriented Rehabilitation Program for Stroke. PMID- 27380355 TI - Cadaver Exome Sequencing for Teaching First-Year Medical Students. PMID- 27380356 TI - Task-Oriented Rehabilitation Program for Stroke--Reply. PMID- 27380357 TI - Public Health and Human Rights. PMID- 27380358 TI - Cadaver Exome Sequencing for Teaching First-Year Medical Students--Reply. PMID- 27380360 TI - Misspelled Author Name. PMID- 27380359 TI - Public Health and Human Rights--Reply. PMID- 27380361 TI - Additional Author Affiliation. PMID- 27380363 TI - The Epidemic of Infantile Paralysis. PMID- 27380364 TI - JAMA PATIENT PAGE. End-of-Life Care. PMID- 27380365 TI - Corrigendum. PMID- 27380366 TI - Developmental changes in carbon and nitrogen metabolism affect tea quality in different leaf position. AB - Leaf position represents a specific developmental stage that influences both photosynthesis and respiration. However, the precise relationships between photosynthesis and respiration in different leaf position that affect tea quality are largely unknown. Here, we show that the effective quantum yield of photosystem II [PhiPSII] as well as total chlorophyll concentration (TChl) of tea leaves increased gradually with leaf maturity. Moreover, respiration rate (RR) together with total nitrogen concentration (TN) decreased persistently, but total carbon remained unchanged during leaf maturation. Analyses of major N-based organic compounds revealed that decrease in TN was attributed to a significant decrease in the concentration of caffeine and amino acids (AA) in mature leaves. Furthermore, soluble sugar (SS) decreased, but starch concentration increased with leaf maturity, indicating that source-sink relationship was altered during tea leaf development. Detailed correlation analysis showed that PhiPSII was negatively correlated with RR, SS, starch, tea polyphenol (TP), total catechins and TN, but positively correlated with TChl; while RR was positively correlated with TN, SS, TP and caffeine, but negatively correlated with TChl and starch concentrations. Our results suggest that biosynthesis of chlorophyll, catechins and polyphenols is closely associated with photosynthesis and respiration in different leaf position that greatly influences the relationship between primary and secondary metabolism in tea plants. PMID- 27380367 TI - Structural insights into the catalytic reaction trigger and inhibition of D-3 hydroxybutyrate dehydrogenase. AB - D-3-Hydroxybutyrate dehydrogenase catalyzes the reversible conversion of acetoacetate and D-3-hydroxybutyrate. These ketone bodies are both energy-storage forms of acetyl-CoA. In order to clarify the structural mechanisms of the catalytic reaction with the cognate substrate D-3-hydroxybutyrate and of the inhibition of the reaction by inhibitors, the enzyme from Alcaligenes faecalis has been analyzed by X-ray crystallography in liganded states with the substrate and with two types of inhibitor: malonate and methylmalonate. In each subunit of the tetrameric enzyme, the substrate is trapped on the nicotinamide plane of the bound NAD(+). An OMIT map definitively shows that the bound ligand is D-3 hydroxybutyrate and not acetoacetate. The two carboxylate O atoms form four hydrogen bonds to four conserved amino-acid residues. The methyl group is accommodated in the nearby hydrophobic pocket so that the formation of a hydrogen bond from the OH group of the substrate to the hydroxy group of Tyr155 at the active centre is facilitated. In this geometry, the H atom attached to the C(3) atom of the substrate in the sp(3) configuration is positioned at a distance of 3.1 A from the nicotinamide C(4) atom in the direction normal to the plane. In addition, the donor-acceptor relationship of the hydrogen bonds suggests that the Tyr155 OH group is allowed to ionize by the two donations from the Ser142 OH group and the ribose OH group. A comparison of the protein structures with and without ligands indicates that the Gln196 residue of the small movable domain participates in the formation of additional hydrogen bonds. It is likely that this situation can facilitate H-atom movements as the trigger of the catalytic reaction. In the complexes with inhibitors, however, their principal carboxylate groups interact with the enzyme in a similar way, while the interactions of other groups are changed. The crucial determinant for inhibition is that the inhibitors have no active H atom at C(3). A second determinant is the Tyr155 OH group, which is perturbed by the inhibitors to donate its H atom for hydrogen-bond formation, losing its nucleophilicity. PMID- 27380368 TI - Crystal structure of the cyan fluorescent protein Cerulean-S175G. AB - Enhanced cyan fluorescent protein (ECFP) was derived from Aequorea victoria green fluorescent protein (avGFP), notably with S65T/Y66W mutations. Its chromophore consists of a tripeptide comprised of Thr65, Trp66 and Gly67 (TWG) residues, while that of avGFP consists of a Ser65, Tyr66 and Gly67 (SYG) tripeptide. Cerulean and SCFP3A were derived from ECFP-S72A/H148D (a double mutation) with additional Y145A and S175G mutations, respectively, while Cerulean-S175G has both mutations (Y145A and S175G). The crystal structures of these ECFP variants at neutral pH were reported to adopt two distinct major conformations called ECFP and Cerulean. In this study, Cerulean-S175G was revealed to adopt only the Cerulean conformation, while Cerulean has been reported to adopt both the ECFP and the Cerulean conformations in its crystal structures. Sharing the same S175G mutation with SCFP3A, Cerulean-S175G showed a slightly increased quantum yield, like SCFP3A, but did not adopt the ECFP conformation adopted by SCFP3A. Detailed comparison of Cerulean-S175G and other ECFP variants revealed that the notable conformational changes in ECFP variants can be understood mainly in terms of the interaction between the Trp66 residue of the chromophore and residues 145-148 of beta-strand 7. PMID- 27380369 TI - Crystal structure of truncated aspartate transcarbamoylase from Plasmodium falciparum. AB - The de novo pyrimidine-biosynthesis pathway of Plasmodium falciparum is a promising target for antimalarial drug discovery. The parasite requires a supply of purines and pyrimidines for growth and proliferation and is unable to take up pyrimidines from the host. Direct (or indirect) inhibition of de novo pyrimidine biosynthesis via dihydroorotate dehydrogenase (PfDHODH), the fourth enzyme of the pathway, has already been shown to be lethal to the parasite. In the second step of the plasmodial pyrimidine-synthesis pathway, aspartate and carbamoyl phosphate are condensed to N-carbamoyl-L-aspartate and inorganic phosphate by aspartate transcarbamoylase (PfATC). In this paper, the 2.5 A resolution crystal structure of PfATC is reported. The space group of the PfATC crystals was determined to be monoclinic P21, with unit-cell parameters a = 87.0, b = 103.8, c = 87.1 A, alpha = 90.0, beta = 117.7, gamma = 90.0 degrees . The presented PfATC model shares a high degree of homology with the catalytic domain of Escherichia coli ATC. There is as yet no evidence of the existence of a regulatory domain in PfATC. Similarly to E. coli ATC, PfATC was modelled as a homotrimer in which each of the three active sites is formed at the oligomeric interface. Each active site comprises residues from two adjacent subunits in the trimer with a high degree of evolutional conservation. Here, the activity loss owing to mutagenesis of the key active-site residues is also described. PMID- 27380370 TI - Crystal structure of a thiolase from Escherichia coli at 1.8 A resolution. AB - Thiolases catalyze the Claisen condensation of two acetyl-CoA molecules to give acetoacetyl-CoA, as well as the reverse degradative reaction. Four genes coding for thiolases or thiolase-like proteins are found in the Escherichia coli genome. In this communication, the successful cloning, purification, crystallization and structure determination at 1.8 A resolution of a homotetrameric E. coli thiolase are reported. The structure of E. coli thiolase co-crystallized with acetyl-CoA at 1.9 A resolution is also reported. As observed in other tetrameric thiolases, the present E. coli thiolase is a dimer of two tight dimers and probably functions as a biodegradative enzyme. Comparison of the structure and biochemical properties of the E. coli enzyme with those of other well studied thiolases reveals certain novel features of this enzyme, such as the modification of a lysine in the dimeric interface, the possible oxidation of the catalytic Cys88 in the structure of the enzyme obtained in the presence of CoA and active-site hydration. The tetrameric enzyme also displays an interesting departure from exact 222 symmetry, which is probably related to the deformation of the tetramerization domain that stabilizes the oligomeric structure of the protein. The current study allows the identification of substrate-binding amino-acid residues and water networks at the active site and provides the structural framework required for understanding the biochemical properties as well as the physiological function of this E. coli thiolase. PMID- 27380371 TI - Structure of a double hexamer of the Pyrococcus furiosus minichromosome maintenance protein N-terminal domain. AB - The crystal structure of the N-terminal domain of the Pyrococcus furiosus minichromosome maintenance (MCM) protein as a double hexamer is described. The MCM complex is a ring-shaped helicase that unwinds DNA at the replication fork of eukaryotes and archaea. Prior to replication initiation, the MCM complex assembles as an inactive double hexamer at specific sites of DNA. The presented structure is highly consistent with previous MCM double-hexamer structures and shows two MCM hexamers with a head-to-head interaction mediated by the N-terminal domain. Minor differences include a diminished head-to-head interaction and a slightly reduced inter-hexamer rotation. PMID- 27380372 TI - LCP crystallization and X-ray diffraction analysis of VcmN, a MATE transporter from Vibrio cholerae. AB - Multidrug and toxic compound extrusion (MATE) transporters, one of the multidrug exporter families, efflux xenobiotics towards the extracellular side of the membrane. Since MATE transporters expressed in bacterial pathogens contribute to multidrug resistance, they are important therapeutic targets. Here, a MATE transporter homologue from Vibrio cholerae, VcmN, was overexpressed in Escherichia coli, purified and crystallized in lipidic cubic phase (LCP). X-ray diffraction data were collected to 2.5 A resolution from a single crystal obtained in a sandwich plate. The crystal belonged to space group P212121, with unit-cell parameters a = 52.3, b = 93.7, c = 100.2 A. As a result of further LCP crystallization trials, crystals of larger size were obtained using sitting-drop plates. X-ray diffraction data were collected to 2.2 A resolution from a single crystal obtained in a sitting-drop plate. The crystal belonged to space group P212121, with unit-cell parameters a = 61.9, b = 91.8, c = 100.9 A. The present work provides valuable insights into the atomic resolution structure determination of membrane transporters. PMID- 27380373 TI - Exogenous acetate ion reaches the type II copper centre in CueO through the water excretion channel and potentially affects the enzymatic activity. AB - The acetate-bound form of the type II copper was found in the X-ray structure of the multicopper oxidase CueO crystallized in acetate buffer in addition to the conventional OH(-)-bound form as the major resting form. The acetate ion was retained bound to the type II copper even after prolonged exposure of a CueO crystal to X-ray radiation, which led to the stepwise reduction of the Cu centres. However, in this study, when CueO was crystallized in citrate buffer the OH(-)-bound form was present exclusively. This fact shows that an exogenous acetate ion reaches the type II Cu centre through the water channel constructed between domains 1 and 3 in the CueO molecule. It was also found that the enzymatic activity of CueO is enhanced in the presence of acetate ions in the solvent water. PMID- 27380374 TI - The galactoside 2-alpha-L-fucosyltransferase FUT1 from Arabidopsis thaliana: crystallization and experimental MAD phasing. AB - The plant cell wall is a complex network of polysaccharides made up of cellulose, hemicelluloses and pectins. Xyloglucan (XyG), which is the main hemicellulosic component of dicotyledonous plants, has attracted much attention for its role in plant development and for its many industrial applications. The XyG-specific fucosyltransferase (FUT1) adds a fucose residue from GDP-fucose to the 2-O position of the terminal galactosyl residues on XyG side chains. Recombinant FUT1 from Arabidopsis thaliana was crystallized in two different crystal forms, with the best diffracting crystals (up to 1.95 A resolution) belonging to the monoclinic space group P21, with unit-cell parameters a = 87.6, b = 84.5, c = 150.3 A, beta = 96.3 degrees . Ab initio phases were determined using a two wavelength anomalous dispersion experiment on a tantalum bromide-derivatized crystal with data collected at the rising and descending inflection points of the Ta white line. An interpretable electron-density map was obtained after elaborate density modification. Model completion and structural analysis are currently under way. PMID- 27380375 TI - Crystallographic analysis of a subcomplex of the transsulfursome with tRNA for Cys-tRNA(Cys) synthesis. AB - In most organisms, Cys-tRNA(Cys) is directly synthesized by cysteinyl-tRNA synthetase (CysRS). Many methanogenic archaea, however, use a two-step, indirect pathway to synthesize Cys-tRNA(Cys) owing to a lack of CysRS and cysteine biosynthesis systems. This reaction is catalyzed by O-phosphoseryl-tRNA synthetase (SepRS), Sep-tRNA:Cys-tRNA synthase (SepCysS) and SepRS/SepCysS pathway enhancer (SepCysE) as the transsulfursome, in which SepCysE connects both SepRS and SepCysS. On the transsulfursome, SepRS first ligates an O-phosphoserine to tRNA(Cys), and the mischarged intermediate Sep-tRNA(Cys) is then transferred to SepCysS, where it is further modified to Cys-tRNA(Cys). In this study, a subcomplex of the transsulfursome with tRNA(Cys) (SepCysS-SepCysE-tRNA(Cys)), which is involved in the second reaction step of the indirect pathway, was constructed and then crystallized. The crystals diffracted X-rays to a resolution of 2.6 A and belonged to space group P6522, with unit-cell parameters a = b = 107.2, c = 551.1 A. The structure determined by molecular replacement showed that the complex consists of a SepCysS dimer, a SepCysE dimer and one tRNA(Cys) in the asymmetric unit. PMID- 27380376 TI - Cryoannealing-induced space-group transition of crystals of the carbonic anhydrase psCA3. AB - Cryoannealing has been demonstrated to improve the diffraction quality and resolution of crystals of the beta-carbonic anhydrase psCA3 concomitant with a change in space group. After initial flash-cooling in a liquid-nitrogen cryostream an X-ray diffraction data set from a psCA3 crystal was indexed in space group P21212 and was scaled to 2.6 A resolution, but subsequent cryoannealing studies revealed induced protein rearrangements in the crystal contacts, which transformed the space group to I222, with a corresponding improvement of 0.7 A in resolution. Although the change in diffraction resolution was significant, only minor changes in the psCA3 structure, which retained its catalytic 'open' conformation, were observed. These findings demonstrate that cryoannealing can be successfully utilized to induce higher diffraction-quality crystals while maintaining enzymatically relevant conformations and may be useful as an experimental tool for structural studies of other enzymes where the initial diffraction quality is poor. PMID- 27380377 TI - Over Ten Years of Experience with a Modified Right Atrial Anastomosis in Orthotopic Heart Transplantation: Follow-up and Comparison with the Biatrial and Bicaval Technique. AB - BACKGROUND: In 1997, a modified right atrial anastomosis (cavoatrial technique) for orthotopic heart transplantation (oHTx) was first developed in our institution. The purpose of this study is to report our long-term experience with this technique compared with biatrial and bicaval technique. METHODS: Retrospectively, 202 consecutive oHTx between 1997 and 2013 were analyzed. The applied transplantation techniques were biatrial (n = 108), bicaval (n = 22), and cavoatrial (n = 72). RESULTS: Demographic data were similar in all groups. The cardiopulmonary bypass and cross-clamp time were significantly shorter in the biatrial group. Follow-up echocardiographic examination showed excellent results in all groups with no relevant differences. After 1 year, occurrence of severe tricuspid regurgitation (biatrial 1.9% vs bicaval 0.0% vs cavoatrial 1.4%) was low in all groups. Rate of permanent pacemaker implantations was also low (12.0% vs 5.0% vs 11.1%). There were no significant differences in survival between the groups. CONCLUSION: The cavoatrial technique can be a safe and simple alternative for heart transplantation. Easy handling and similar reduced postoperative complications encourage the use of this technique. PMID- 27380378 TI - Quality of Life and Anxiety in Younger Patients after Biological versus Mechanical Aortic Valve Replacement. AB - Background Since biological valve recipients are likely to need a redo procedure in the future for valve deterioration, we hypothesized patients might be more fearful about the progression of their disease than patients after aortic valve replacement (AVR) with a mechanical valve. The aim of this study is to compare the quality of life (QOL) and anxiety in patients who have undergone biological versus mechanical AVR. Method A total of 56 patients after mechanical AVR (mean age: 64.4 +/- 8.17 years) and 66 patients after biological AVR (mean age: 64.8 +/ 11.05 years) received three questionnaires 5.66 (+/- 2.68) years after surgery, including: The short form-36 (SF-36) to assess QOL, the fear of progression questionnaire (FOP), and the cardiac anxiety questionnaire (CAQ) to assess general anxiety, anxiety related to cardiac symptoms, and anxiety about progression of heart disease and valve and anticoagulation-specific questions. Results No significant differences were found for all categories of the SF-36. The FOP showed significantly favorable values for the biological AVR group. The CAQ showed a tendency in the subscale "avoidance" (i.e., avoidance of pulse increase) and "attention" towards more favorable values for the biological AVR group. Conclusions In contrast to our hypothesis, patients after mechanical AVR show significantly higher anxiety values for the FOP, and a tendency toward higher values for "avoidance" (i.e., avoidance of pulse increase). Partnership concerns, especially in terms of sexuality can be explained by factors that are recognizable for the partner, such as valve sound. These data provide evidence that factors that are continuously present after mechanical AVR, such as valve sound or anticoagulation might affect wellbeing stronger than the certainty of reoperation in the future after biological AVR. We conclude that implantation of a biological prosthesis can be justified in younger patients with regards to QOL. PMID- 27380380 TI - Nontuberculous Mycobacteria Infection and Prognosis after Surgery of Lung Cancer: A Retrospective Study. AB - To investigate the association between pulmonary nontuberculous mycobacteria infection (PNTMI) and prognosis after pulmonary resection for non small cell lung cancer (NSCLC), we retrospectively analyzed 391 consecutive patients with NSCLC who underwent surgery. Subjects were grouped based on with/without PNTMI defined by two criteria (12 and 23 PNTMI subjects). Kaplan-Meier analysis showed no significant difference between the two groups regarding overall survival (p = 0.800 and p = 0.912 by two criteria). PNTMI was not identified as a significant factor associated with prognosis by either univariate or multivariate analysis (hazard ratio [HR] = 0.950 and HR = 0.948, respectively). PMID- 27380379 TI - Suture or Stapling Are Superior in Comparison to Bipolar Sealing for Closing the Bronchi. AB - Background Every anatomical lung resection requires the airtight closure of at least one bronchus. In current clinical practice, these bronchi are sealed with sutures or staplers. This study investigated in an ex vivo pig model whether a new bipolar sealing device MARSEAL (KLS Martin, Tuttlingen, Germany) could be an alternative for this purpose. Methods Complete bronchial trees were prepared free from pig heart-lung blocks that were removed at a slaughterhouse. These preparations were taken to the laboratory, and main, lobar, and segmental bronchi were closed using sutures, staples, or bipolar sealing. Each trachea was then intubated and connected to a ventilating device. The initial airtight closure of the bronchus was first tested with lung-protective ventilation. After 15 minutes of ventilation, the inspiratory ventilation pressure was slowly increased and the burst pressure (in mbar) was recorded. Each group included 12 bronchus closures. Group mean burst pressures were compared using a nonparametric test (Mann-Whitney U test). The significance level was p < 0.05. Results The main bronchi closed both stapler magazines or sutures were all initially airtight during ventilation. The mean burst pressure was 60 +/- 0 mbar for staplers and 57.92 +/- 5.8 mbar for sutures. In contrast, 50% of main bronchi sealed with MARSEAL devices (5 or 10 mm) leaked air from the beginning. This was also noted in all lobar bronchi sealed with the MARSEAL 5-mm device and 80% of those sealed with the MARSEAL 10 mm device. The mean burst pressure of initially airtight lobar bronchi was 12.7 +/- 7.25 mbar. In contrast, all segmental bronchi (mean width: 1.6 cm) were airtight when ventilated. Mean burst pressure was 14.64 +/- 9.1 mbar with the MARSEAL 5-mm device and 29.64 +/- 21.3 mbar with the MARSEAL 10-mm device. Histological investigation of the preparations (with hematoxylin and eosin staining) showed intact cartilaginous structures that were largely unaffected by bipolar coagulation. The airtight sealing of the segmental bronchi resulted from fusion of the peribronchial tissue and not the cartilage. Conclusion Bipolar sealing is an inappropriate tool for the closure of the bronchi in comparison to suture or stapling. PMID- 27380381 TI - Molecular characterization and expression analysis of AMPK alpha subunit isoform genes from Scophthalmus maximus responding to salinity stress. AB - AMP-activated protein kinase (AMPK) is a highly conserved and multi-functional protein kinase that plays important roles in both intracellular energy balance and cellular stress response. In the present study, molecular characterization, tissue distribution and gene expression levels of the AMPK alpha1 and alpha2 genes from turbot (Scophthalmus maximus) under salinity stress are described. The complete coding regions of the AMPK alpha1 and alpha2 genes were isolated from turbot through degenerate primers in combination with RACE using muscle cDNA. The complete coding regions of AMPK alpha1 (1722 bp) and alpha2 (1674 bp) encoded 573 and 557 amino acids peptides, respectively. Multiple alignments, structural analysis and phylogenetic tree construction indicated that S. maximus AMPK alpha1 and alpha2 shared a high amino acid identity with other species, especially fish. AMPK alpha1 and alpha2 genes could be detected in all tested tissues, indicating that they are constitutively expressed. Salinity challenges significantly altered the gene expression levels of AMPK alpha1 and alpha2 mRNA in a salinity- and time dependent manners in S. maximus gill tissues, suggesting that AMPK alpha1 and alpha2 played important roles in mediating the salinity stress in S. maximus. The expression levels of AMPK alpha1 and alpha2 mRNA were a positive correlation with gill Na+, K+-ATPase activities. These findings will aid our understanding of the molecular mechanism of juvenile turbot in response to environmental salinity changes. PMID- 27380382 TI - Catalytic Reduction of 4-Nitrophenol Using Silver Nanoparticles with Adjustable Activity. AB - We report on the development of ultrasmall core-shell silver nanoparticles synthesized by an upscaled modification of the polyol process. It is foreseen to use these thoroughly characterized particles as reference material to compare the catalytic and biological properties of functionalized silver nanoparticles. Small angle X-ray scattering (SAXS) analysis reveals a narrow size distribution of the silver cores with a mean radius of Rc = 3.0 nm and a distribution width of 0.6 nm. Dynamic light scattering (DLS) provides a hydrodynamic radius of RH = 10.0 nm and a PDI of 0.09. The particles' surface is covered with poly(acrylic acid) (PAA) forming a shell with a thickness of 7.0 nm, which provides colloidal stability lasting for more than 6 months at ambient conditions. The PAA can be easily exchanged by biomolecules to modify the surface functionality. Replacements of PAA with glutathione (GSH) and bovine serum albumin (BSA) have been performed as examples. We demonstrate that the silver particles effectively catalyze the reduction of 4-nitrophenol to 4-aminophenol with sodium borohydride. With PAA as stabilizer, the catalytic activity of 436 +/- 24 L g(-1) s(-1) is the highest reported in the literature for silver nanoparticles. GSH and BSA passivate the surface substantially, resulting in a catalytic activity of 77.6 +/ 0.9 and 3.47 +/- 0.50 L g(-1) s(-1), respectively. PMID- 27380383 TI - [Disseminated necrobiotic xanthogranuloma]. AB - Necrobiotic xanthogranuloma is a rare non-Langerhans-cell histiocytosis. A 62 year-old woman presented with yellowish erythematous plaques, nodules, and papules in the periorbital region and the extremities. She had a nodular tumor grown on the left upper lid that clinically resembled a keratoacanthoma. Histologically it was a xanthogranulomatous lesion. She suffered from monoclonal gammopathy of unknown significance of kappa-type. Treatment was realized with a combination of systemic dapsone/prednisolone and topical corticosteroids. PMID- 27380384 TI - [Trichophyton species of Arthroderma benhamiae : Clinical therapeutic aspects of a new pathogen in dermatology]. AB - Cutaneous infections with Trichophyton species of Arthroderma (A.) benhamiae are increasingly being detected in Germany. This dermatophyte typically causes tinea corporis, tinea faciei or tinea capitis with in part heavy clinical manifestation like kerion celsi. In special cases diagnosis and therapy can be difficult. In this article, four clinical cases are presented, whereby attention is given to special clinical situations and therapeutic aspects with regard to Trichophyton species of A. benhamiae: Case 1: Kerion celsi by in a 6-year-old boy; Case 2: Deep trichophytia at the mons pubis in a 32-year-old man working in a pet shop and his 27-year-old female partner; Case 3: Tinea manuum in a 7-year-old girl; Case 4: Tinea corporis in an 8-year-old girl. PMID- 27380385 TI - Mediterranean spotted fever-like illness in Sardinia, Italy: a clinical and microbiological study. AB - INTRODUCTION: Rickettsioses represent a group of emerging infectious diseases in Europe. Climate changes and the anthropization of rural environment have favored vectors' biological cycle and geographic spread. In Sardinia, Mediterranean spotted fever (MSF) is endemic and represents an important public health problem. PURPOSE: We investigated the etiology and the clinical presentation of MSF-like illness in northern Sardinia by enrolling patients admitted to the Infectious Disease Unit of the University of Sassari. RESULTS: Diagnostic tests included ELISA, Indirect immunofluorescence (IFI), DNA isolation from blood and from eschar samples with real-time PCR and genotyping. Eighty-seven patients with a mean age of 53 +/- 14 years, of whom 65 (75 %) males, were included in the study. The most common diagnosis was MSF (79 %), followed by Q fever (8 %), and anaplasmosis (2 %). A tache noire was found in 58 % of rickettioses and 28 % of Coxiella burnetii infections. MSF was confirmed in 47 % of the cases by IFI and 43 % by ELISA antibody tests. The isolation of rickettsial DNA from the eschar was positive in 10/13 (77 %) of the cases due to Rickettsia conorii. Using this method, we identified the first case of R. monacensis infection in Italy. CONCLUSIONS: In conclusion, antibody-based tests confirmed the diagnosis in less than 50 % of the cases, whereas DNA isolation confirmed the diagnosis in 77 % of tested cases and allowed the identification of a new pathogenic species in Italy. Therefore, DNA isolation should be implemented to better identify the etiology of MSF-like illnesses and help the clinician in the management of patients. PMID- 27380386 TI - Characteristics and management of patients with influenza in a German hospital during the 2014/2015 influenza season. AB - The objective of this study was to review the management of patients with influenza during the influenza season 2014/2015 (n = 197). Our study revealed a high rate of healthcare-associated influenza infection (35.5 %) and a correlation between the total number of patients with HA influenza and the number of nurses on sick leave. The results of the study underline the importance of strict hygiene management. Furthermore, widespread influenza vaccination for both high risk patients and health care workers is recommended. PMID- 27380387 TI - Anticoagulation in the Very Old. PMID- 27380388 TI - A Radical-Mediated Pathway for the Formation of [M + H](+) in Dielectric Barrier Discharge Ionization. AB - Active capillary plasma ionization is a highly efficient ambient ionization method. Its general principle of ion formation is closely related to atmospheric pressure chemical ionization (APCI). The method is based on dielectric barrier discharge ionization (DBDI), and can be constructed in the form of a direct flow through interface to a mass spectrometer. Protonated species ([M + H](+)) are predominantly formed, although in some cases radical cations are also observed. We investigated the underlying ionization mechanisms and reaction pathways for the formation of protonated analyte ([M + H](+)). We found that ionization occurs in the presence and in the absence of water vapor. Therefore, the mechanism cannot exclusively rely on hydronium clusters, as generally accepted for APCI. Based on isotope labeling experiments, protons were shown to originate from various solvents (other than water) and, to a minor extent, from gaseous impurities and/or self-protonation. By using CO2 instead of air or N2 as plasma gas, additional species like [M + OH](+) and [M - H](+) were observed. These gas phase reaction products of CO2 with the analyte (tertiary amines) indicate the presence of a radical-mediated ionization pathway, which proceeds by direct reaction of the ionized plasma gas with the analyte. The proposed reaction pathway is supported with density functional theory (DFT) calculations. These findings add a new ionization pathway leading to the protonated species to those currently known for APCI. Graphical Abstract ?. PMID- 27380389 TI - The Effects of Added Hydrogen on Noble Gas Discharges Used as Ambient Desorption/Ionization Sources for Mass Spectrometry. AB - We demonstrate the effectiveness of using hydrogen-doped argon as the support gas for the dielectric barrier discharge (DBD) ambient desorption/ionization (ADI) source in mass spectrometry. Also, we explore the chemistry responsible for the signal enhancement observed when using both hydrogen-doped argon and hydrogen doped helium. The hydrogen-doped argon was tested for five analytes representing different classes of molecules. Addition of hydrogen to the argon plasma gas enhanced signals for gas-phase analytes and for analytes coated onto glass slides in positive and negative ion mode. The enhancements ranged from factors of 4 to 5 for gas-phase analytes and factors of 2 to 40 for coated slides. There was no significant increase in the background. The limit of detection for caffeine was lowered by a factor of 79 using H2/Ar and 2 using H2/He. Results are shown that help explain the fundamental differences between the pure-gas discharges and those that are hydrogen-doped for both argon and helium. Experiments with different discharge geometries and grounding schemes indicate that observed signal enhancements are strongly dependent on discharge configuration. Graphical Abstract ?. PMID- 27380390 TI - Suicidal Ideation is Associated with Limited Engagement in HIV Care. AB - PHQ-9 data from persons living with HIV (PLWH, n = 4099) being screened for depression in three clinics in the southeastern USA were used to determine the prevalence of suicidal ideation (SI). SI was reported by 352 (8.6 %); associated with <3 years since HIV diagnosis (1.69; 95 %CI 1.35, 2.13), and HIV RNA >50 copies/ml (1.70, 95 %CI 1.35, 2.14). Data from PLWH enrolled in a depression treatment study were used to determine the association between moderate-to-high risk SI (severity) and SI frequency reported on PHQ-9 screening. Over forty percent of persons reporting that SI occurred on "more than half the days" (by the PHQ-9) were assessed as having a moderate-to-high risk for suicide completion during the Mini International Neuropsychiatric Interview. SI, including moderate to-high risk SI, remains a significant comorbid problem for PLWH who are not fully stabilized in care (as indicated by detectable HIV RNA or HIV diagnosis for less than 3 years). PMID- 27380391 TI - Closing the Gap? The HIV Continuum in Care for African-American Men Who Have Sex with Men, San Francisco, 2004-2014. AB - We examined trends in the HIV continuum in care in the National HIV Behavioral Surveillance surveys for MSM in San Francisco from 2004 to 2014. In 2004, HIV positive African-American MSM were less likely to be diagnosed (42.9 vs. 87.5 %, p = 0.003), linked to care (42.9 vs. 85.7 %, p = 0.007), or to have ever used antiretroviral treatment (ART) (28.6 vs. 69.6 %, p = 0.032) compared to white MSM. By 2014, these gaps had narrowed but not closed, including diagnosis (85.7 vs. 100 %, Fisher's exact p = 0.106), linkage to care (85.7 vs. 96.8 %, Fisher's exact p = 0.290), and ART use (85.7 vs. 94.9 %, Fisher's exact p = 0.369). PMID- 27380392 TI - Comparative assessment of phthalate removal and risk in biological wastewater treatment systems of developing countries and small communities. AB - Phthalates are widely used in plastic and personnel care products. Being non steroid endocrine disrupting compounds, their exposure have toxic effects on aquatic life and human health. The aim of this study was a comparative assessment of their fate and risk in full scale wastewater treatment along with influence of seasonal variations. Four priority phthalates, Diethylphthalate (DEP), Dibutylphthalate (DBP), Benzylbutyl phthalate (BBP) and Diethylhexyl phthalate (DEHP) were chosen for this study and wastewater treatment plants investigated were designed as nutrient removal based sequencing batch reactor (SBR), conventional activated sludge process (ASP) and up flow anaerobic sludge blanket (UASB) with polishing pond. Results showed that the main removal mechanism of phthalates was biotransformation with removal contribution of 74% in SBR, 65% in conventional ASP and 37% in UASB. Overall removal of phthalates was maximum in the treatment combination of UASB and pond (83%) followed by SBR (80%) and conventional ASP (74%). Seasonal influences on occurrence, removal and risk of these phthalates were also studied. The concentration of DEP, DBP and DEHP in untreated wastewater increased by 2, 7 and 2MUg/L, respectively in summer. However in sludge, only large molecular weight phthalates BBP and DEHP increased in winter by 3mg/kg and 12mg/kg, respectively. Seasonal variations in removal of phthalates were discrepant in each process with better removal during summer. Risk assessment of phthalates to aquatic life showed that there is no potential risk of DEP, DBP and BBP from effluents of treatment plants however risk quotient of DEHP was in the range of 27-73 in both seasons which indicate probable risk to aquatic organisms. Phthalate risk to human beings estimated by daily intake of phthalates was in the range of 0.3+/-0.1 to 20+/-0.7ng/kg/d and far below their respective reference dosages, demonstrating the potential of these treatment plants to reduce the risk of phthalates. PMID- 27380393 TI - Development of a multimedia model (POPsLTEA) to assess the influence of climate change on the fate and transport of polycyclic aromatic hydrocarbons in East Asia. AB - A dynamic multimedia model (POPsLTEA) for an East Asia region was developed and evaluated to quantitatively assess how climate change (CC) alters the environmental fate and transport dynamics of 16 polycyclic aromatic hydrocarbons (PAHs) in air, water, soil, and sediment. To cover the entire model domain (25 degrees N-50 degrees N and 98 degrees E-148 degrees E) where China, Japan, and South and North Koreas are of primary concern, a total of 5000 main cells of 50km*50km size were used while 1008 cells of a finer spatial resolution (12.5km*12.5km) was nested for South Korea (33 degrees N-38 degrees N and 126 degrees E-132 degrees E). Most of the predicted concentrations agreed with the observed values within one order of magnitude with a tendency of overestimation for air and sediment. Prediction of the atmospheric concentration was statistically significant in both coincidence and association, suggesting the model's potential to successfully predict the fate and transport of the PAHs as influenced by CC. An example study of benzo(a)pyrene demonstrates that direction and strength of the CC influence on the pollution levels vary with the location and environmental media. As compared to the five year period of 2011 to 2015, the changes across the model domain in the annual geometric mean concentration over the years of 2021 through 2100 were predicted to range from 88% to 304%, from 84% to 109%, from 32% to 362%, and from 49% to 303%, in air, soil, surface water, and sea water, respectively, under the scenario of RCP8.5. PMID- 27380394 TI - Influence of regional hydrogeological systems at a local scale: Analyzing the coupled effects of hydrochemistry and biological activity in a Fe and CO2 rich spring. PMID- 27380395 TI - The impact of a high magnitude flood on metal pollution in a shallow subtropical estuarine embayment. AB - Drought-breaking floods pose a risk to coastal water quality as sediments, nutrients, and pollutants stored within catchments during periods of low flow are mobilized and delivered to coastal waters within a short period of time. Here we use subtidal surface sediment surveys and sediment cores to explore the effects of the 2011 Brisbane River flood on trace metals zinc (Zn), lead (Pb), copper (Cu), nickel (Ni), chromium (Cr), manganese (Mn), and phosphorus (P) deposition in Moreton Bay, a shallow subtropical bay in eastern Australia. Concentrations of Zn, Cu, and Pb in sediments in central Moreton Bay derived from the 2011 flood were the highest yet observed in the Bay. We suggest flushing of metal rich sediments which had accumulated on the Brisbane River floodplain and in its estuary during the preceding 10 to 40years of low flows to be the primary source of this increase. This highlights the importance of intermittent high magnitude floods in tidally influenced rivers in controlling metal transport to coastal waters in subtropical regions. PMID- 27380396 TI - Analysis, occurrence, fate and risks of proton pump inhibitors, their metabolites and transformation products in aquatic environment: A review. AB - Proton pump inhibitors (PPIs) which include omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole, are extensively used for the relief of gastro-intestinal disorders. Despite their high worldwide consumption, PPIs are extensively metabolized in human bodies and therefore are not regularly detected in monitoring studies. Very recently, however, it has been shown that some omeprazole metabolites may enter and are likely to persist in aquatic environment. Hence, to fully assess the environmental exposures and risks associated with PPIs, it is important to better understand and evaluate the fate and behavior not only of the parent compound but also of their metabolites and their transformation products arising from biotic and abiotic processes (hydrolysis, photodegradation, biodegradation etc.) in the environment. In this light, the purpose of this review is to summarize the present state of knowledge on the introduction and behavior of these chemicals in natural and engineering systems and highlight research needs and gaps. It draws attention to their transformation, the increase contamination by their metabolites/TPs in different environmental matrices and their potential adverse effects in the environment. Furthermore, existing research on analytical developments with respect to sample treatment, separation and detection of PPIs and their metabolites/TPs is provided. PMID- 27380397 TI - PROMIS Computer Adaptive Tests Compared With Time to Brake in Patients With Complex Lower Extremity Trauma. AB - OBJECTIVES: To compare the PROMIS Physical Function and Pain Interference Computer Adaptive Tests (PROMIS PF CAT and PROMIS PI CAT) with time to brake (TTB) in patients with complex lower extremity traumas for evaluating whether patients can safely return to driving. DESIGN: Prospective. SETTING: Level-1 trauma center. PATIENTS: Sixty-three patients with lower extremity injuries to the pelvis, acetabulum, hip, femur, knee, tibia/fibula, ankle, and foot within 15 weeks of treatment. INTERVENTION: The TTB of patients with complex lower extremity trauma were tested at various time points postoperatively on a computerized driving simulator. Patients concurrently completed PROMIS PF CAT and PROMIS PI CAT. MAIN OUTCOME MEASURE: Correlations between TTB, PROMIS PF CAT, and PROMIS PI CAT. RESULTS: The mean TTB for the healthy control group was 0.61 seconds. There was a statistically significant correlation between time since treatment and TTB (B = -0.008 s/d; P = 0.041) for right-sided lower extremity injuries below the knee (tibia/fibula, ankle, foot). TTB for right-sided injuries below the knee also significantly correlated with PROMIS PI CAT (B = 0.022; P = 0.029). The PROMIS PI CAT value was 43 when the healthy control group TTB was equal to 0.61 seconds. CONCLUSIONS: This study suggests that the PROMIS PI CAT can be used as an adjunct to the TTB in assessing whether a patient can safely return to driving. PMID- 27380398 TI - Predictors of Nonunion and Infectious Complications in Patients With Posttraumatic Subtalar Arthrodesis. AB - OBJECTIVE: The objective of the present study was (1) to identify predictors of both nonunion and postoperative wound infections (POWI) and (2) to assess the union and complication rate following posttraumatic subtalar arthrodesis (STA). DESIGN: Retrospective comparative cohort study. SETTING: Level 1 trauma center. PATIENTS: All consecutive adult patients with STA following traumatic injuries between 2000 and May 2015. INTERVENTION: STA for posttraumatic deformities. MAIN OUTCOME MEASUREMENTS: Union (described as a combination of radiographic signs of osseous bridging and a clinically fused joint) and POWI as classified by the Centers for Disease and Control. RESULTS: A total number of 93 (96 feet) patients met the inclusion criteria. Union was achieved in 89% of patients. For primary, secondary in situ, and secondary correction arthrodesis, these percentages were 94%, 84,% and 90%, respectively (NS). The union rate significantly increased over time (P = 0.02). In 17 patients (18%), a POWI occurred, of which 2 were classified as superficial and 15 as deep POWIs. The POWI rate did not differ between the groups. Alcohol, nicotine, and drug abuse were not significantly associated with the occurrence of POWIs. Patients with an open fracture or an infection following open reduction internal fixation had a greater risk of a POWI following STA (P = 0.03 and P = 0.04, respectively). CONCLUSIONS: We could not identify predictors for nonunion. In 18% of the patients, an infectious complication following surgery occurred. Patients with an open fracture or an infection after primary surgical treatment (ie, open reduction internal fixation) have a higher chance of POWIs following STA. The union rate following posttraumatic STA is 89%. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 27380399 TI - Does fibrin sealant applied to the kidney wound of a young rat affect the development of this organ? A comparative study. AB - OBJECTIVE: The aim of the study was to compare the results of the application of fibrin sealant and absorbable interrupted sutures and to evaluate the impact of the kidney wound closure method on the further development of the organ in young rats. MATERIALS AND METHODS: In 140 rats, a longitudinal bipolar incision of the renal parenchyma was made. In the study group the wound was closed using a fibrin sealant, whereas in the control group single absorbable sutures were applied to the renal parenchyma. Intravenous pyelography, postmortem and histopathological examinations were carried out 4 weeks and 6 months after the surgery. RESULTS: The blood loss was smaller and the time of procedure shorter in the study group than in controls, and the differences were statistically significant. Both 4 weeks and 6 months after the surgery, the differences in the kidney dimensions and kidney weight between the two groups were statistically significant. The differences increased after a longer period of time following the surgery. The histopathological examination revealed that in the case of animals with surgical sutures applied to the wound, the rate of resorptive granulomas and abscess formation was higher, whereas kidneys with fibrin sealant applied to the wound featured a high number of lymphocytic infiltrations of minor severity. CONCLUSIONS: The application of the fibrin sealant simplified the surgical procedure, shortened its duration, and provided hemostasis and permanent closure of the wound. The fibrin sealant facilitates the process of wound healing. The application of a fibrin sealant, compared to surgical sutures, improved the growth of rat kidneys without impairing their functions. PMID- 27380401 TI - [Not Available]. PMID- 27380402 TI - [Not Available]. PMID- 27380403 TI - [Not Available]. PMID- 27380400 TI - Role of the intrarenal renin-angiotensin system in the progression of renal disease. AB - The intrarenal renin-angiotensin system (RAS) has many well-documented pathophysiologic functions in both blood pressure regulation and renal disease development. Angiotensin II (Ang II) is the major bioactive product of the RAS. It induces inflammation, renal cell growth, mitogenesis, apoptosis, migration, and differentiation. In addition, Ang II regulates the gene expression of bioactive substances and activates multiple intracellular signaling pathways that are involved in renal damage. Activation of the Ang II type 1 (AT1) receptor pathway results in the production of proinflammatory mediators, intracellular formation of reactive oxygen species, cell proliferation, and extracellular matrix synthesis, which in turn facilities renal injury. Involvement of angiotensinogen (AGT) in intrarenal RAS activation and development of renal disease has previously been reported. Moreover, studies have demonstrated that the urinary excretion rates of AGT provide a specific index of the intrarenal RAS status. Enhanced intrarenal AGT levels have been observed in experimental models of renal disease, supporting the concept that AGT plays an important role in the development and progression of renal disease. In this review, we focus on the role of intrarenal RAS activation in the pathophysiology of renal disease. Additionally, we explored the potential of urinary AGT as a novel biomarker of intrarenal RAS status in renal disease. PMID- 27380404 TI - [Not Available]. PMID- 27380405 TI - [Not Available]. PMID- 27380406 TI - Ingenane Diterpenoids. AB - Despite a more recent isolation and chemical characterization when compared to phorbol, along with its chemical instability, limited distribution in Nature, and scarce availability, ingenol is the only Euphorbia diterpenoid that has undergone successful pharmaceutical development, with ingenol 3-angelate (ingenol mebutate, Picato((r))) entering the pharmaceutical market in 2012 for the treatment of actinic keratosis. The phytochemical, chemical, and biological literature on members of the ingenane class of diterpenoids is reviewed from their first isolation in 1968 through 2015, highlighting unresolved issues both common to phorboids (biogenesis, relationship between molecular targets, and in vivo activity) and specific to ingenol derivatives (two-dimensional representation, in out stereoisomerism, versatility of binding mode to PKC, and inconsistencies in the structural elucidation of some classes of derivatives). The biogenesis of ingenol is discussed in the light of the Jakupovic proposal of a dissection between the formation of the macrocyclic Euphorbia diterpenoids and the phorboids, and the clinical development of ingenol mebutate is chronicled in the light of its "reverse-pharmacology" focus. PMID- 27380408 TI - Correction: Correction: The Spread of Dengue in an Endemic Urban Milieu-The Case of Delhi, India. AB - [This corrects the article DOI: 10.1371/journal.pone.0152847.]. PMID- 27380407 TI - The Laurencia Paradox: An Endless Source of Chemodiversity. AB - Nature, the most prolific source of biological and chemical diversity, has provided mankind with treatments for health problems since ancient times and continues to be the most promising reservoir of bioactive chemicals for the development of modern drugs. In addition to the terrestrial organisms that still remain a promising source of new bioactive metabolites, the marine environment, covering approximately 70% of the Earth's surface and containing a largely unexplored biodiversity, offers an enormous resource for the discovery of novel compounds. According to the MarinLit database, more than 27,000 metabolites from marine macro- and microorganisms have been isolated to date providing material and key structures for the development of new products in the pharmaceutical, food, cosmeceutical, chemical, and agrochemical sectors. Algae, which thrive in the euphotic zone, were among the first marine organisms that were investigated as sources of food, nutritional supplements, soil fertilizers, and bioactive metabolites.Red algae of the genus Laurencia are accepted unanimously as one of the richest sources of new secondary metabolites. Their cosmopolitan distribution, along with the chemical variation influenced to a significant degree by environmental and genetic factors, have resulted in an endless parade of metabolites, often featuring multiple halogenation sites.The present contribution, covering the literature until August 2015, offers a comprehensive view of the chemical wealth and the taxonomic problems currently impeding chemical and biological investigations of the genus Laurencia. Since mollusks feeding on Laurencia are, in many cases, bioaccumulating, and utilize algal metabolites as chemical weaponry against natural enemies, metabolites of postulated dietary origin of sea hares that feed on Laurencia species are also included in the present review. Altogether, 1047 secondary metabolites, often featuring new carbocyclic skeletons, have been included.The chapter addresses: (1) the "Laurencia complex", the botanical description and the growth and population dynamics of the genus, as well as its chemical diversity and ecological relations; (2) the secondary metabolites, which are organized according to their chemical structures and are classified into sesquiterpenes, diterpenes, triterpenes, acetogenins, indoles, aromatic compounds, steroids, and miscellaneous compounds, as well as their sources of isolation which are depicted in tabulated form, and (3) the biological activity organized according to the biological target and the ecological functions of Laurencia metabolites. PMID- 27380409 TI - Emotion and Implicit Timing. AB - This study examined the effects of emotion on implicit timing. In the implicit timing task used, the participants did not receive any temporal instructions. Instead they were simply asked and trained to press a key as quickly as possible after a stimulus (response stimulus) that was separated from a preceding stimulus by a given temporal interval (reference interval duration). However, in the testing phase, the interval duration was the reference interval duration or a shorter or longer interval duration. In addition, the participants attended two sessions: a first baseline session in which no stimulus was presented during the inter-stimulus intervals, and a second emotional session in which emotional facial expressions (angry, neutral and sad facial expressions) were presented during these intervals. Results showed faster RTs for interval durations close to the reference duration in both the baseline and the emotional conditions and yielded a U-shaped curve. This suggests that implicit processing of time persists in emotional contexts. In addition, the RT was faster for the facial expressions of anger than for those of neutrality and sadness. However, the U-shaped RT curve did not peak clearly at a shorter interval duration for the angry than for the other facial expressions. This lack of time distortion in an implicit timing task in response to arousing emotional stimuli questions the idea of an automatic speeding-up of the interval clock system involved in the representation of time. PMID- 27380410 TI - Cell Size Critically Determines Initial Retention of Bone Marrow Mononuclear Cells in the Heart after Intracoronary Injection: Evidence from a Rat Model. AB - Intracoronary injection of bone marrow mononuclear cells (BMMNC) is an emerging treatment for heart failure. Initial donor cell retention in the heart is the key to the success of this approach, but this process remains insufficiently characterized. Although it is assumed that cell size of injected cells may influence their initial retention, no scientific evidence has been reported. We developed a unique model utilizing an ex-vivo rat heart perfusion system, enabling quantitative assessment of retention of donor cells after intracoronary injection. The initial (5 minutes after intracoronary injection) retention rate of BMMNC was as low as approximately 20% irrespective of donor cell doses injected (1*106, 8*106, 4*107). Quantitative cell-size assessment revealed a positive relationship between the size of BMMNC and retention ratio; larger subpopulations of BMMNC were more preferentially retained compared to smaller ones. Furthermore, a larger cell type-bone marrow-derived mesenchymal stromal cells (median size = 11.5MUm versus 7.0MUm for BMMNC)-had a markedly increased retention rate (77.5+/-1.8%). A positive relationship between the cell size and retention ratio was also seen in mesenchymal stromal cells. Flow-cytometric studies showed expression of cell-surface proteins, including integrins and selectin-ligands, was unchanged between pre-injection BMMNC and those exited from the heart, suggesting that biochemical interaction between donor cells and host coronary endothelium is not critical for BMMNC retention. Histological analyses showed that retained BMMNC and mesenchymal stromal cells were entrapped in the coronary vasculature and did not extravasate by 60 minutes after transplantation. Whilst BMMNC did not change coronary flow after intracoronary injection, mesenchymal stromal cells reduced it, suggesting coronary embolism, which was supported by the histological finding of intravascular cell-clump formation. These data indicate that cell-size dependent, passive (mechanical), intravascular entrapment is responsible for the initial donor cell retention after intracoronary injection of BMMNC in the heart having normal vasculatures (at least). PMID- 27380412 TI - Reply to the Letter by Uzun and Pehlivan Entitled 'Characteristics of Hyperautofluorescent Choroidal Vessels within the Macular Atrophic Area Using Spectral-Domain Optical Coherence Tomography'. PMID- 27380411 TI - Cdo Regulates Surface Expression of Kir2.1 K+ Channel in Myoblast Differentiation. AB - A potassium channel Kir2.1-associated membrane hyperpolarization is required for myogenic differentiation. However the molecular regulatory mechanisms modulating Kir2.1 channel activities in early stage of myogenesis are largely unknown. A cell surface protein, Cdo functions as a component of multiprotein cell surface complexes to promote myogenesis. In this study, we report that Cdo forms a complex with Kir2.1 during myogenic differentiation, and is required for the channel activity by enhancing the surface expression of Kir2.1 in the early stage of differentiation. The expression of a constitutively active form of the upstream kinase for p38MAPK, MKK6(EE) can restore Kir2.1 activities in Cdo depleted C2C12 cells, while the treatment with a p38MAPK inhibitor, SB203580 exhibits a similar effect of Cdo depletion on Kir2.1 surface expression. Furthermore, Cdo-/- primary myoblasts, which display a defective differentiation program, exhibit a defective Kir2.1 activity. Taken together, our results suggest that a promyogenic Cdo signaling is critical for Kir2.1 activities in the induction of myogenic differentiation. PMID- 27380413 TI - Next-Generation "-omics" Approaches Reveal a Massive Alteration of Host RNA Metabolism during Bacteriophage Infection of Pseudomonas aeruginosa. AB - As interest in the therapeutic and biotechnological potentials of bacteriophages has grown, so has value in understanding their basic biology. However, detailed knowledge of infection cycles has been limited to a small number of model bacteriophages, mostly infecting Escherichia coli. We present here the first analysis coupling data obtained from global next-generation approaches, RNA Sequencing and metabolomics, to characterize interactions between the virulent bacteriophage PAK_P3 and its host Pseudomonas aeruginosa. We detected a dramatic global depletion of bacterial transcripts coupled with their replacement by viral RNAs over the course of infection, eventually leading to drastic changes in pyrimidine metabolism. This process relies on host machinery hijacking as suggested by the strong up-regulation of one bacterial operon involved in RNA processing. Moreover, we found that RNA-based regulation plays a central role in PAK_P3 lifecycle as antisense transcripts are produced mainly during the early stage of infection and viral small non coding RNAs are massively expressed at the end of infection. This work highlights the prominent role of RNA metabolism in the infection strategy of a bacteriophage belonging to a new characterized sub family of viruses with promising therapeutic potential. PMID- 27380414 TI - Photodegradation of Polyfluorinated Dibenzo-p-Dioxins in Organic Solvents: Experimental and Theoretical Studies. AB - Eighteen polyfluorinated dibenzo-p-dioxins (PFDDs) were synthesized by pyrolysis of fluorophenols. Using a 500 W Xe lamp as the light source, the PFDDs photodegradation kinetics in n-hexane were investigated. The photolysis reactions obeyed the pseudo-first-order rate equation, and higher fluorinated PFDDs tended to photolyze more slowly. Theoretically calculated parameters reflecting the molecular structural properties were used to develop a new model of PFDDs photolysis rates. The results indicated that the substitution pattern for fluorine atoms and the C-O bond length were major factors in the photolysis of PFDDs. We selected octafluorinated dibenzo-p-dioxin (OFDD) as a representative PFDDs to explore the influence of solvent on the photolysis rate of PFDDs, and the results indicated that neither the polarity nor donor hydrogen of organic solvents are independent influencing factors. Mechanistic pathways for the photolysis of OFDD in n-hexane were first studied. The results indicated that photodegradation of OFDD produces octafluorinated dihydroxybiphenyls, octafluorinated phenoxyphenols, and fluorinated phenols. The major pathway for photodegradation of OFDD was C-O bond cleavage. Defluorination reactions did not occur during the photolysis process. PMID- 27380415 TI - Comparing airway topical anaesthesia techniques for awake fibreoptic intubation. PMID- 27380416 TI - Erratum to: Microsolvation and hydration enthalpies of CaC2O4(H2O) n (n = 0-16) and C2O42-(H2O) n (n = 0-14): an ab initio study. PMID- 27380417 TI - Assessing the Effects of the New Cooperative Medical Scheme on Alleviating the Health Payment-Induced Poverty in Shaanxi Province, China. AB - BACKGROUND: Disease has become one of the key causes of falling into poverty in rural China. The poor households are even more likely to suffer. The New Cooperative Medical Scheme (NCMS) has been implemented to provide rural residents financial protection against health risks. This study aims to assess the effect of the NCMS on alleviating health payment-induced poverty in the Shaanxi Province of China. METHODS: The data was drawn from the 5th National Health Service Survey of Shaanxi Province, conducted in 2013. In total, 41,037 individuals covered by NCMS were selected. Poverty headcount ratio (HCR), poverty gap and mean positive poverty gap were used for measuring the incidence, depth and intensity of poverty, respectively. The differences on poverty measures pre- and post- insurance reimbursement indicate the effectiveness of alleviating health payment induced poverty under NCMS. RESULTS: For the general insured, 5.81% of households fell below the national poverty line owing to the health payment; this HCR dropped to 4.84% after insurance reimbursement. The poverty HCRs for the insured that had hospitalization in the past year dropped from 7.50% to 2.09% after reimbursement. With the NCMS compensation, the poverty gap declined from 42.90 Yuan to 34.49 Yuan (19.60% decreased) for the general insured and from 57.48 Yuan to 10.01 Yuan (82.59% decreased) for the hospital admission insured. The mean positive poverty gap declined 3.56% and 37.40% for two samples, respectively. CONCLUSION: The NCMS could alleviate the health payment-induced poverty. The effectiveness of alleviating health payment-induced poverty is greater for hospital admission insured than for general insured, mainly because NCMS compensates for serious diseases. Our study suggests that a more comprehensive insurance benefit package design could further improve the effectiveness of poverty alleviation. PMID- 27380418 TI - Correction: Effects of Pyrolysis Temperature on Product Yields and Energy Recovery from Co-Feeding of Cotton Gin Trash, Cow Manure, and Microalgae: A Simulation Study. AB - [This corrects the article DOI: 10.1371/journal.pone.0152230.]. PMID- 27380419 TI - A Calcium-Ion-Stabilized Lipase from Pseudomonas stutzeri ZS04 and its Application in Resolution of Chiral Aryl Alcohols. AB - An extracellular organic solvent-tolerant lipase-producing bacterium was isolated from oil-contaminated soil samples and was identified taxonomically as Pseudomonas stutzeri, from which the lipase was purified and exhibited maximal activity at temperature of 50 degrees C and pH of 9.0. Meanwhile, the lipase was stable below or at 30 degrees C and over an alkaline pH range (7.5-11.0). Ca2+ could significantly improve the lipase thermal stability which prompts a promising application in biocatalysis through convenient medium engineering. The lipase demonstrated striking features such as distinct stability to the most tested hydrophilic and hydrophobic solvents (25 %, v/v), and DMSO could activate the lipase dramatically. In the enzyme-catalyzed resolution, lipase ZS04 manifested excellent enantioselective esterification toward the (R)-1-(4 methoxyphenyl)-ethanol (MOPE), a crucial chiral intermediate in pharmaceuticals as well as in other analogs with strict substrate specificity and theoretical highest conversion yield. This strong advantage over other related schemes made lipase ZS04 a promising biocatalyst in organic synthesis and pharmaceutical applications. PMID- 27380420 TI - Enzymatic Production of Glutathione by Bifunctional gamma-Glutamylcysteine Synthetase/Glutathione Synthetase Coupled with In Vitro Acetate Kinase-Based ATP Generation. AB - Glutathione (gamma-glutamyl-L-cysteinylglycine, GSH) is a pharmaceutical compound often used in food additives and the cosmetics industry. GSH can be produced biologically from L-glutamic acid, L-cysteine, and glycine through an enzymatic process traditionally involving two sequential adenosine triphosphate (ATP) dependent reactions catalyzed by gamma-glutamylcysteine synthetase (gamma-GCS or GSHI, EC 6.3.2.2) and GSH synthetase (GS or GSHII, EC 6.3.2.3). Here, we report the enzymatic production of GSH by recombinant cell-free bifunctional gamma glutamylcysteine synthetase/glutathione synthetase (gamma-GCS-GS or GshF) coupled with in vitro acetate kinase-based ATP generation. GSH production by an acetate kinase-integrated Escherichia coli Rosetta(DE3) mutant expressing Streptococcus thermophilus GshF reached 18.3 +/- 0.1 g l-1 (59.5 +/- 0.3 mM) within 3 h, with a molar yield of 0.75 +/- 0.00 mol mol-1 added cysteine and a productivity of 6.1 +/- 0.0 g l-1 h-1. This is the highest GSH titer reported to date. This newly developed biocatalytic process offers a promising approach for meeting the industrial requirements for GSH production. PMID- 27380421 TI - Understanding the Nonproductive Enzyme Adsorption and Physicochemical Properties of Residual Lignins in Moso Bamboo Pretreated with Sulfuric Acid and Kraft Pulping. AB - In this work, to elucidate why the acid-pretreated bamboo shows disappointingly low enzymatic digestibility comparing to the alkali-pretreated bamboo, residual lignins in acid-pretreated and kraft pulped bamboo were isolated and analyzed by adsorption isotherm to evaluate their extents of nonproductive enzyme adsorption. Meanwhile, physicochemical properties of the isolated lignins were analyzed and a relationship was established with non-productive adsorption. Results showed that the adsorption affinity and binding strength of cellulase on acid-pretreated bamboo lignin (MWLa) was significantly higher than that on residual lignin in pulped bamboo (MWLp). The maximum adsorption capacity of cellulase on MWLp was 129.49 mg/g lignin, which was lower than that on MWLa (160.25 mg/g lignin). When isolated lignins were added into the Avicel hydrolysis solution, the inhibitory effect on enzymatic hydrolysis efficiency of MWLa was found to be considerably stronger than that with MWLp. The cellulase adsorption on isolated lignins was correlated positively with hydrophobicity, phenolic hydroxyl group, and degree of condensation but negatively with surface charges and aliphatic hydroxyl group. These results suggest that the higher nonproductive cellulase adsorption and physicochemical properties of residual lignin in acid-pretreated bamboo may be responsible for its disappointingly low enzymatic digestibility. PMID- 27380423 TI - Zika virus: Facing a new threat. PMID- 27380422 TI - Molecular Signals Involved in Human B Cell Migration into the Retina: In Vitro Investigation of ICAM-1, VCAM-1, and CXCL13. AB - PURPOSE: B cells participate in diverse retinal immunopathologies. Endothelial adhesion molecules and chemokines direct leukocyte trafficking. We examined the involvement of three molecular signals in retinal transendothelial migration of human B cells: ICAM-1, VCAM-1, and CXCL13. METHODS: Peripheral blood B cells were isolated by negative selection. Migration was studied in transwells populated with human retinal endothelial monolayers, using antibody to block ICAM-1 or VCAM 1. Retinal expression of CXCL13 was investigated. RESULTS: B cells crossed retinal endothelium. ICAM-1 blockade significantly reduced migration when results for all subjects were combined, and for a majority when results were analyzed by individual. This effect was irrespective of the presence or absence of CXCL13, although CXCL13 increased migration. CXCL13 was detected in neural retina and retinal pigment epithelium. Endothelial cells of some retinal vessels presented CXCL13 protein. CONCLUSION: ICAM-1 blockade may be an effective treatment in some patients with retinal diseases that involve B cells. PMID- 27380424 TI - Inconsistency and social decision making in patients with Borderline Personality Disorder. AB - Inconsistent social behavior is a core psychopathological feature of borderline personality disorder. The goal of the present study was to examine inconsistency in social decision-making using simple economic social experiments. We investigated the decisions of 17 female patients with BPD, 24 patients with major depressive disorder (MDD), and 36 healthy controls in three single shot economic experiments measuring trust, cooperation, and punishment. BPD severity was assessed using the Zanarini Rating Scale for BPD. Investments across identical one-shot trust and punishment games were significantly more inconsistent in BPD patients than in controls. Such inconsistencies were only found in the social risk conditions of the trust and punishment conditions but not in the non-social control conditions. MDD patients did not show such inconsistencies. Furthermore, social support was negatively correlated with inconsistent decision-making in the trust and punishment game, which underscores the clinical relevance of this finding. PMID- 27380426 TI - The Surface Science of Catalysis and More, Using Ultrathin Oxide Films as Templates: A Perspective. AB - Surface science has had a major influence on the understanding of processes at surfaces relevant to catalysis. Real catalysts are complex materials, and in order to approach an understanding at the atomic level, it is necessary in a first step to drastically reduce complexity and then systematically increase it again in order to capture the various structural and electronic factors important for the function of the real catalytic material. The use of thin oxide films as templates to mimic three-dimensional supports as such or for metal particles as well as to model charge barriers turns out to be appropriate to approach an understanding of metal-support interactions. Thin oxide films also exhibit properties in their own right that turn out to be relevant in catalysis. Thin oxide film formation may also be used to create unique two-dimensional materials. The present perspective introduces the subject using case studies and indicates possible routes to further apply this approach successfully. PMID- 27380425 TI - Protein Sialylation Regulates a Gene Expression Signature that Promotes Breast Cancer Cell Pathogenicity. AB - Many mechanisms have been proposed for how heightened aerobic glycolytic metabolism fuels cancer pathogenicity, but there are still many unexplored pathways. Here, we have performed metabolomic profiling to map glucose incorporation into metabolic pathways upon transformation of mammary epithelial cells by 11 commonly mutated human oncogenes. We show that transformation of mammary epithelial cells by oncogenic stimuli commonly shunts glucose-derived carbons into synthesis of sialic acid, a hexosamine pathway metabolite that is converted to CMP-sialic acid by cytidine monophosphate N-acetylneuraminic acid synthase (CMAS) as a precursor to glycoprotein and glycolipid sialylation. We show that CMAS knockdown leads to elevations in intracellular sialic acid levels, a depletion of cellular sialylation, and alterations in the expression of many cancer-relevant genes to impair breast cancer pathogenicity. Our study reveals the heretofore unrecognized role of sialic acid metabolism and protein sialylation in regulating the expression of genes that maintain breast cancer pathogenicity. PMID- 27380427 TI - LONG-TERM FOLLOW-UP OF PATIENTS WITH RETINITIS PIGMENTOSA TYPE 12 CAUSED BY CRB1 MUTATIONS: A Severe Phenotype With Considerable Interindividual Variability. AB - PURPOSE: To examine the long-term clinical course and variability in a large pedigree segregating CRB1 type autosomal recessive retinitis pigmentosa. METHODS: An observational case study of 30 patients with CRB1 type autosomal recessive retinitis pigmentosa, homozygous for the CRB1 c.3122T > C; p.(Met1041Thr) mutation from a Dutch genetically isolated population in which the CRB1 gene was originally identified. The authors evaluated medical records, analyzed a questionnaire, and performed a comprehensive ophthalmic examination, including optical coherence tomography. RESULTS: Mean follow-up was 19 years (range 0-45 years, SD 15 years). With aging, patients showed progressive visual decline, deterioration of visual fields, increasing narrowing of the anterior chamber, increased prevalence of cataract, and an increase in the amount of intraretinal pigmentations. Fifty percent of patients had a visual acuity of <=0.3 at Age 18 and of <=0.1 at Age 35. Electroretinogram responses were severely reduced or absent already at a young age and optical coherence tomography showed increased retinal thickness with often cystoid maculopathy at young age, and thinning of the retina and disorientation of the photoreceptor layer in the late stages. The clinical course showed considerable interindividual variability, but intraindividual similarity between both eyes was the rule. CONCLUSION: The wide and variable clinical spectrum in patients with the same CRB1 mutation supports the hypothesis that the CRB1 type autosomal recessive retinitis pigmentosa phenotype is modulated by other factors. The clinical variability will make it harder to evaluate the effect of (upcoming) therapies for retinitis pigmentosa, although because of the intraindividual similarity between both eyes, the contralateral eye can be used as an excellent internal control. PMID- 27380428 TI - POSTERIOR EYE SEGMENT COMPLICATIONS RELATED TO ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION. AB - PURPOSE: To identify complications in the posterior eye segment in patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: This retrospective cohort study enrolled 747 patients with hematologic disease who had undergone allogeneic HSCT at Seoul St. Mary's Hospital from January 2009 to December 2012. The posterior eye segment complications were evaluated by reviewing information in medical records at the Department of Hematology and Ophthalmology, including the types, onset times, locations, and resolution times of the complications according to the treatment periods for HSCT; in addition, a subgroup analysis was performed. RESULTS: Among the 635 included patients, 48 (7.6%) experienced complications related to HSCT in the posterior eye segment. Twenty patients were diagnosed with retinal hemorrhage, 16 with cytomegalovirus (CMV) retinitis, and 5 with uveitis. Six patients (37.5%) with retinal hemorrhage had a lesion in Zone 1 and took more time to recover from this complication. Retinal tear (1/16, 6.3%) and rhegmatogenous retinal detachment (2/16, 12.5%) were observed in the patients with CMV retinitis. Among the 20 patients with retinal hemorrhage, 18 (90.0%) had thrombocytopenia, 14 (70.0%) had pancytopenia, and 7 (35.0%) had profound cytopenia. Cytomegalovirus viremia was detected in 16 (72.7%) of the 22 patients with inflammation associated complications. CONCLUSION: Understanding of each patient's general condition, which is affected by the specific procedures used for HSCT, is important for the diagnosis and management of transplantation-related complications in the posterior eye segment. PMID- 27380429 TI - TOWARDS A TREATMENT FOR DIABETIC RETINOPATHY: Intravitreal Toxicity and Preclinical Safety Evaluation of Inducible Nitric Oxide Synthase Inhibitors. AB - BACKGROUND: The purpose of this study is to determine the maximum tolerated dose of a single intravitreal injection of aminoguanidine and 1400W, 2 inhibitors of inducible nitric oxide synthase, in rabbit eyes. Inhibition of inducible nitric oxide synthase has already been shown to be beneficial in various animal models of diabetic eye disease. METHODS: Groups of 4 New Zealand white rabbits were injected with balanced salt solution in the right eye and a single dose of either aminoguanidine (5, 1, 0.25 mg) or 1400W (2 mg and 0.4 mg) in the left eye. Toxicity was assessed by slit-lamp and fundus examination, intraocular pressure and pachymetric measurements, and electrophysiologic and histologic analysis. RESULTS: Eyes injected with high doses of aminoguanidine (5 mg) or 1400W (2 mg) demonstrated severe retinal vascular attenuation and infarction. Lower doses of intravitreal aminoguanidine (1 mg) and 1400W (0.4 mg) caused no significant toxic ocular effects in rabbit eyes. CONCLUSION: If the difference in vitreal volume between rabbit eyes and human eyes is taken into account, aminoguanidine (2.7 mg) and 1400W (1 mg) would be reasonable intravitreal doses to test for safety and efficacy in early clinical trials. PMID- 27380430 TI - RETICULAR PSEUDODRUSEN ARE NOT A PREDICTIVE FACTOR FOR THE 1-YEAR RESPONSE TO INTRAVITREAL RANIBIZUMAB IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION. AB - PURPOSE: To investigate reticular pseudodrusen (RPD) as a potential baseline factor predictive of a poor 1-year response to intravitreal ranibizumab in eyes with neovascular age-related macular degeneration. METHODS: Retrospective, monocentric case series including 98 consecutive naive neovascular age-related macular degeneration patients. Presence of RPD was assessed by two graders based on color, blue-light, fundus autofluorescence pictures, and spectral-domain optical coherence tomography. A correlation between the presence of RPD and the visual change was investigated. Other baseline characteristics studied in a monovariate and multivariate analysis were the following: age, gender, affected side, loading dose, type of neovascularization, presence of retinal pigment epithelial detachment >250 MUm, subretinal or intraretinal fluid, blood over >50% of the lesion, and subfoveal choroidal thickness. RESULTS: The presence of RPD was not associated with a visual change (P = 0.96), but with a thin subfoveal choroidal thickness at baseline (P < 0.0001). The monovariate analysis showed that the presence of blood at baseline was associated with visual gain (P = 0.007). CONCLUSION: The presence of RPD at baseline was not identified as a factor associated with a poor 1-year response to ranibizumab in eyes with neovascular age-related macular degeneration. Studies with a longer follow-up may be needed to assess the impact of RPD on the visual prognosis of eyes with neovascular age-related macular degeneration. PMID- 27380431 TI - CHORIORETINAL WHITE DOT LESIONS IN EYES WITH MULTIFOCAL CHOROIDITIS AND TILTED DISK SYNDROME WITH INFERIOR STAPHYLOMA. AB - PURPOSE: To assess the influence of tilted disk syndrome (TDS) and inferior staphyloma on the macular clinical expression of MFC. METHODS: Medical charts of patients with MFC examined since 2009 were reviewed retrospectively. All patients underwent standard examination and multimodal imaging including fundus color photography, fundus autofluorescence, and spectral domain optical coherence tomography. Two groups of patients were compared : Group 1 with TDS and inferior staphyloma and Group 2 without. The number of MFC spots were counted and normalized to the surface area in a circle centered about the fovea. In Group 1, the number of lesions inside the staphyloma was compared with that outside the staphyloma. RESULTS: At baseline, 8 eyes in Group 1 had a mean (+/-SD) higher number of chorioretinal lesions outside the staphyloma (14.5 [+/-7.2]) than within the staphyloma (5 [+/-5.5]) (P = 0.017). All 11 eyes in Group 2 had chorioretinal lesions homogeneously distributed in the posterior pole. Eyes with TDS and inferior staphyloma developed choroidal neovascularization more frequently (6/8 eyes) than eyes without TDS (5/11 eyes) (P = 0.026). CONCLUSION: Inferior staphyloma associated with TDS could modulate the clinical expression of the inflammatory and neovascular process in eyes with MFC. PMID- 27380432 TI - Psychopathy and low communion: An overlooked and underappreciated core feature. AB - Psychopathy is a personality disorder that is robustly linked to interpersonal difficulties, delinquency, aggression, and general antisocial conduct. Previous research has explored a number of potential deficits underlying these behaviors including reduced fear, impaired emotional responding, and poor response modulation. Drawing from extant personality work that has demonstrated the importance of interpersonal antagonism as a core feature of psychopathy, the present project examines low communion as a potential core feature of the disorder in a novel manner-using a social discounting lab task. This possibility was examined in 195 undergraduate students (49% male) via a multimethod approach. In addition to a measure of psychopathy, participants completed a novel social discounting laboratory task designed to measure communion. Participants also completed self-report measures of communion and related constructs including the NEO Personality Inventory-Revised, Multidimensional Personality Questionnaire, and Interpersonal Adjective Scales. Results indicate that psychopathic individuals are lower in their level of communion and value social relationships less. Dysfunctions in communion should be studied more specifically in psychopathy as it may be a core feature of the disorder. (PsycINFO Database Record PMID- 27380433 TI - Role of neutralizing anti-murine interleukin-17A monoclonal antibody on chronic ozone-induced airway inflammation in mice. AB - Exposure to ozone has led to airway inflammation and airway hyperresponsiveness, which potential mechanisms relate to ozone-induced oxidative stress. IL-17 is a growing target for autoimmune and inflammatory diseases. The aim of the study was to examine the inhibitory effects of anti-murine interleukin-17A monoclonal antibody (IL-17mAb) on adverse effects of ozone which are noted above. After C57/BL6 mice were exposed to ozone (2.5ppm; 3h) for 12 times over 6 weeks, IL 17mAb, PBS was intraperitoneally injected into mice 1h after ozone or air exposure for 6 weeks and mice were studied 24h after final exposure, monitoring bronchial responsiveness, airway inflammatory cells, lung histology, levels of neutrophil-related chemokine and proinflammatory cytokines in bronchoalveolar lavage (BAL) fluid and serum, the expression of IL-17A mRNA and protein, glucocorticoid receptors (GR), and the phosphorylation of p38MAPK in lung tissues. The administration of IL-17mAb reduced the ozone-induced increases in total cells, especially neutrophils; decreased levels of cytokines, including IL 8 in BAL fluid, IL-8 and IL-17A in serum; mitigated the severity of airway hyperresponsiveness; attenuated lung inflammation scores and histologic analysis confirmed the suppression of lung inflammation, compared with the administration of a control PBS. Exposure to ozone results in increases in IL-17A production rate, mRNA and protein levels of IL-17A and the protein level of GR. These effects were halted and reversed by IL-17mAb treatment. Furthermore, IL-17mAb also reduced the phosphorylation of p38MAPK. Therefore, we conclude that IL-17mAb may be a useful therapy in ozone-related diseases, including COPD. PMID- 27380434 TI - Stent Retrievers for Treating Anterior Circulation Acute Ischemic Stroke-Reply. PMID- 27380435 TI - Effects of Vehicles and Enhancers on the Skin Permeation of Phytoestrogenic Diarylheptanoids from Curcuma comosa. AB - Curcuma comosa (C. comosa) is widely used in traditional medicine as a dietary supplement for health promotion in postmenopausal women in Thailand. It contains several diarylheptanoids, which are considered to be a novel class of phytoestrogens. However, the diarylheptanoids isolated from the plant rhizome are shown to have low oral bioavailability and faster elimination characteristics. The aim of this study was to investigate the permeation behavior of the active compounds of diarylheptanoids. The effects of binary vehicle systems and permeation enhancers on diarylheptanoids permeation and accumulation within the skin were studied using side-by-side diffusion cells through the porcine ear skin. Among the tested binary vehicle systems, the ethanol/water vehicle appeared to be the most effective system for diarylheptanoids permeation with the highest flux and shortest lag time. The presence of transcutol in the vehicle system significantly increased diarylheptanoid's permeation and accumulation within the skin in a concentration-dependent manner. Although the presence of terpenes in formulation decreased the flux of diarylheptanoids, it raised the amount of diarylheptanoids retained within the skin substantially. Based on the feasibility of diarylheptanoid permeation, C. comosa extract should be further developed into an effective transdermal product for health benefits and hormone replacement therapy. PMID- 27380436 TI - Improved Flux of Levodopa via Direct Deposition of Solid Microparticles on Nasal Tissue. AB - Epithelial flux and permeability across bovine olfactory tissue were compared when levodopa (L-DOPA) was loaded in different physical states. Aqueous solution of L-DOPA was prepared in Krebs-Ringer buffer (KRB), at a concentration (0.75 mg/mL) verified to be less than the saturation solubility at both 25 and 37 degrees C. Sodium metabisulfite was added to solution to minimize L-DOPA oxidation; chemical stability of aqueous L-DOPA was evaluated using HPLC-UV. Solid-state characterization of unprocessed, dry, crystalline L-DOPA powder was performed using TGA, DSC, PXRD, and optical microscopy to ensure that preparation of L-DOPA microparticles used for diffusion experiments did not elicit a phase change. Measurements of in vitro flux were made for all preparations, using freshly excised bovine olfactory mucosal membrane. Samples obtained from transport studies were analyzed by HPLC-UV. Tissue viability was measured before and after experiments using transdermal epithelial electrical resistance (TEER). The average steady-state flux (J ss ) of L-DOPA from solid microparticles directly deposited on nasal epithelial tissue was 6.08 +/- 0.69 MUg/cm2/min, approximately three times greater than the J ss measured for L-DOPA from solution (2.13 +/- 0.97 MUg/cm2/min). The average apparent permeability coefficient (P app ) of L-DOPA was calculated to be 4.73 * 10-5 cm/s. These findings suggest that nasal delivery of L-DOPA by administration of solid microparticles not only benefits from improved chemical and microbiological stability by avoiding the use of aqueous formulation vehicle but also does not compromise cumulative mass transport across the olfactory membrane. PMID- 27380437 TI - Effects of Protein Conformation, Apparent Solubility, and Protein-Protein Interactions on the Rates and Mechanisms of Aggregation for an IgG1Monoclonal Antibody. AB - Non-native protein aggregation is a key degradation pathway of immunoglobulins. In this work, the aggregation kinetics of an immunoglobulin gamma-1 monoclonal antibody (IgG1 mAb) in different solution environments was monitored over a range of incubation temperatures for up to seven months using size exclusion chromatography. Histidine and citrate buffers with/without sodium chloride were employed to modulate the mAb's conformational stability, solubility (in the presence of polyethylene glycol, PEG), and protein-protein interactions as measured by differential scanning calorimetry, PEG precipitation, and static light scattering, respectively. The effect of these parameters on the mechanism(s) of mAb aggregation during storage at different temperatures was determined using kinetic models, which were used to fit aggregation data to determine rate constants for aggregate nucleation and growth processes. This approach was used to investigate the effects of colloidal protein-protein interactions and solubility values (in PEG solutions) on the mechanisms and rates of IgG1 mAb aggregation as a function of temperature-induced structural perturbations. Aggregate nucleation and growth pathways for this IgG1 mAb were sensitive to temperature and overall conformational stability. Aggregate growth, on the other hand, was also sensitive to conditions affecting the solubility of the mAb, particularly at elevated temperatures. PMID- 27380439 TI - Analysis of minimally invasive directional antennas for microwave tissue ablation. AB - PURPOSE: Microwave ablation (MWA) applicators capable of creating directional heating patterns offer the potential of simplifying treatment of targets in proximity to critical structures and avoiding the need for piercing the tumour volume. This work reports on improved directional MWA antennas with the objectives of minimising device diameter for percutaneous use (<= ~13 gauge) and yielding larger ablation zones. METHODS: Two directional MWA antenna designs, with a modified monopole radiating element and spherical and parabolic reflectors are proposed. A 3D-coupled electromagnetic heat transfer with temperature dependent material properties was implemented to characterise MWA at 40 and 77 W, for 5 and 10 min. Simulations were also used to assess antenna impedance matching within liver, kidney, lung, bone and brain tissue. The two antenna designs were fabricated and experimentally evaluated with ablations in ex vivo tissue at the two power levels and treatment durations (n = 5 repetitions for each group). RESULTS: The computed specific absorption rate (SAR) patterns for both antennas were similar, although simulations indicated slightly greater forward penetration for the parabolic antenna. Based on simulations for antennas inserted within different tissues, the proposed antenna design appears to offer good impedance matching for a variety of tissue types. Experiments in ex vivo tissue showed radial ablation depths of 19 +/- 0.9 mm in the forward direction for the applicator with spherical reflector and 18.7 +/- 0.7 mm for the applicator with parabolic reflector. CONCLUSION: These results suggest the applicator may be suitable for creating localised directional ablation zones for treating small and medium-sized targets with a percutaneous approach. PMID- 27380440 TI - Planimetry of the porta hepatis in biliary atresia. AB - AIMS: Orientation and digital analysis of the biliary remnants in the resected porta hepatis in infants with biliary atresia. METHODS AND RESULTS: Samples were orientated intra-operatively then stained with haematoxylin and eosin and immunostained for cytokeratin 7 (CK7). Sections were then digitized and analysed. Most proximal transected surface area was defined as the porta hepatis area (PHA) and the biliary epithelial area was defined as 'BEA'. Data are quoted as median (range). Non-parametric statistical comparisons were made as appropriate. P < 0.05 was regarded as significant. Thirty-eight infants underwent surgery [median age 53 (16-120) days]. Eight specimens were excluded from the study due to technical reasons, leaving 30 specimens as the study cohort. Median PHA was 70 (30-133) mm2 , median BEA 0.57 (0.07-5.5) mm2 (r = 0.51; P < 0.002). The median BEA/PHA ratio was 9.6 * 10-3 (1.9-104 * 10-3 ). There was a marked correlation of PHA with plasma gamma-glutamyl transpeptidase (r = -0.51; P = 0.001). Both total BEA and the BEA/PHA ratio correlated with alkaline phosphatase (r = -0.35; P = 0.03 and r = -0.47; P = 0.005, respectively). Age at surgery correlated inversely with BEA (r = -0.44; P = 0.01) but not PHA (P = 0.1). CONCLUSIONS: Precise quantification of biliary remnants is possible and correlates with biochemical variables. Values for BEA were associated with and declined demonstrably with increasing age at surgery. PMID- 27380441 TI - HB-EGF embedded in PGA/PLLA scaffolds via subcritical CO2 augments the production of tissue engineered intestine. AB - The ability to deliver sustained-release, biologically active growth factors through custom designed tissue engineering scaffolds at sites of tissue regeneration offers great therapeutic opportunity. Due to the short in vivo half lives of most growth factors, it is challenging to deliver these proteins to sites of interest where they may be used before being degraded. The application of subcritical CO2 uses gas-phase CO2 at subcritical pressures ranging from 41 to 62 bar (595-913 PSI) which avoids foaming by reducing the amount of CO2 dissolved in the polymer and maintains completely reversible plasticization. In the current study, heparin-binding EGF-like growth factor (HB-EGF) was embedded into polyglycolic acid (PGA)/Poly-l-latic acid (PLLA) scaffolds via subcritical CO2 exposure for the production of tissue engineered intestine (TEI). PGA fiber morphology after subcritical CO2 exposure was examined by scanning electron microscopy (SEM) and the distribution of HB-EGF embedded in the scaffold fibers was detected by HB-EGF immunofluorescent staining. In vivo implantation of HB-EGF embedded scaffolds confirmed significantly improved TEI structure as a result of local delivery of the trophic growth factor. These findings may be critical for the production of TEI in the treatment of patients with short bowel syndrome in the future. PMID- 27380438 TI - Water: A Tale of Two Liquids. AB - Water is the most abundant liquid on earth and also the substance with the largest number of anomalies in its properties. It is a prerequisite for life and as such a most important subject of current research in chemical physics and physical chemistry. In spite of its simplicity as a liquid, it has an enormously rich phase diagram where different types of ices, amorphous phases, and anomalies disclose a path that points to unique thermodynamics of its supercooled liquid state that still hides many unraveled secrets. In this review we describe the behavior of water in the regime from ambient conditions to the deeply supercooled region. The review describes simulations and experiments on this anomalous liquid. Several scenarios have been proposed to explain the anomalous properties that become strongly enhanced in the supercooled region. Among those, the second critical-point scenario has been investigated extensively, and at present most experimental evidence point to this scenario. Starting from very low temperatures, a coexistence line between a high-density amorphous phase and a low density amorphous phase would continue in a coexistence line between a high density and a low-density liquid phase terminating in a liquid-liquid critical point, LLCP. On approaching this LLCP from the one-phase region, a crossover in thermodynamics and dynamics can be found. This is discussed based on a picture of a temperature-dependent balance between a high-density liquid and a low-density liquid favored by, respectively, entropy and enthalpy, leading to a consistent picture of the thermodynamics of bulk water. Ice nucleation is also discussed, since this is what severely impedes experimental investigation of the vicinity of the proposed LLCP. Experimental investigation of stretched water, i.e., water at negative pressure, gives access to a different regime of the complex water diagram. Different ways to inhibit crystallization through confinement and aqueous solutions are discussed through results from experiments and simulations using the most sophisticated and advanced techniques. These findings represent tiles of a global picture that still needs to be completed. Some of the possible experimental lines of research that are essential to complete this picture are explored. PMID- 27380442 TI - ZOT-derived peptide and chitosan functionalized nanocarrier for oral delivery of protein drug. AB - In this study, we developed a dual ligand functionalized pluronic-based nanocarrier (NC) for oral delivery of insulin. Chitosan and zonula occludins toxin (ZOT)-derived, tight junction opening peptide were conjugated to NC to increase the permeability of loaded insulin across the small intestine through the paracellular pathway. Surface functionalized NC, either by chitosan or peptide, could modulate the tight junction (TJ) integrity in contrast to no effect of unmodified NC, as evidenced by the change in transepithelial electrical resistance (TEER) and immunostaining of Claudin-4, a tight junction marker, in Caco-2 cell monolayer. On the other hand, dual ligand (chitosan and peptide) functionalized NC significantly further increased the permeation of insulin across Caco-2 cell monolayer. More importantly, insulin loaded, dual ligand functionalized NC could increase the plasma insulin level and efficiently regulate the glycemic response for a prolonged period of time (~1 day) upon oral administration to diabetic rats, whereas delivery of insulin by single ligand functionalized NCs, either by chitosan or peptide, as well as by unmodified NC and free insulin, could not induce the effective regulation of the blood glucose level. The use of fluorescence dye labeled insulin (FITC-insulin) and Cy5.5 labeled NC revealed that both insulin and dual ligand functionalized NC were adequately penetrated across the whole intestine villi in contrast to limited adsorption of insulin and NC mainly onto the epithelial surface of the intestine for single ligand functionalized NCs. These results suggest that dual conjugation of ZOT-derived peptide and chitosan is a promising approach to functionalize the surface of nanocarrier for oral delivery of protein drugs. PMID- 27380444 TI - Hand preference is selectively related to common and internal carotid arterial asymmetry. AB - This study documents relationships between handedness and carotid arterial asymmetries. The article is divided into two sections, considering first geometric (n = 195) and then haemodynamic (n = 228) asymmetries. In the geometric study, diameters, lengths, and angles of the common carotid arteries in left and right-handed participants were measured using computed tomography angiography scans. Resistance to blood flow was calculated according to Poiseuille's formula. In the haemodynamic study, peak systolic and end-diastolic velocity, vessel diameter, and volume flow rate of the common, internal, and external carotid arteries were measured in left and right-handed participants, using Doppler ultrasonography. The findings reveal for the first time that the extracranial arteries supplying the cerebral hemispheres are asymmetrical in a direction that increases blood flow to the hemisphere dominant for handedness. Significant handedness interactions were identified in arterial length, diameter, resistance to blood flow, velocity and flow volume rate (p < .001). Arterial resistance and volume flow rates significantly predicted hand preference and proficiency. Our findings reveal a vascular correlate of handedness, but causality cannot be determined from this study alone. These asymmetries appear to be independent of aortic arch anomalies, suggesting a top-down, possibly demand-driven, pattern of development. PMID- 27380443 TI - Biomimetic cardiovascular stents for in vivo re-endothelialization. AB - The use of cardiovascular stents for rapid in vivo re-endothelialization is a promising strategy for reducing cardiovascular implantation or preventing local thrombus formation and restenosis. Surface-patterned intravascular endoprosthetic stents have been developed to prevent life-threatening complications. In this study, vascular smooth muscle cell (VSMC)-biomimetic surface patterns were fabricated on 316L cardiovascular stents using a femtosecond laser and then implanted into the iliac artery of rabbit. The in vitro data revealed that the bionic surface patterns matched the morphology of the VSMCs well, which promotes the adhesion, proliferation, and migration of human umbilical vein endothelial cells. In addition, the patterned surfaces can significantly enhance re endothelialization. Consequently, the surface biomimetic stent with the VSMC surface pattern is likely an effective approach to ensure rapid re endothelialization and possibly reduce the incidence of in-stent restenosis. PMID- 27380445 TI - Iodine(III)-Catalyzed Cascade Reactions Enabling a Direct Access to beta-Lactams and alpha-Hydroxy-beta-amino Acids. AB - In the presented method, a one-pot metal-free access to beta-lactams is provided. The developed strategy employs a hypervalent iodine(III)-triggered bromination/rearrangement/cyclization cascade reaction that allows the straightforward synthesis of a broad range of structurally different lactams from cheap and easily available imides. This triple cascade reaction is furthermore extendable by an in situ ring-opening reaction, giving direct access to isoserine derivatives from simple imines in a four-step, one-pot reaction. PMID- 27380446 TI - A Wearable Electrochemical Platform for Noninvasive Simultaneous Monitoring of Ca(2+) and pH. AB - Homeostasis of ionized calcium in biofluids is critical for human biological functions and organ systems. Measurement of ionized calcium for clinical applications is not easily accessible due to its strict procedures and dependence on pH. pH balance in body fluids greatly affects metabolic reactions and biological transport systems. Here, we demonstrate a wearable electrochemical device for continuous monitoring of ionized calcium and pH of body fluids using a disposable and flexible array of Ca(2+) and pH sensors that interfaces with a flexible printed circuit board. This platform enables real-time quantitative analysis of these sensing elements in body fluids such as sweat, urine, and tears. Accuracy of Ca(2+) concentration and pH measured by the wearable sensors is validated through inductively coupled plasma-mass spectrometry technique and a commercial pH meter, respectively. Our results show that the wearable sensors have high repeatability and selectivity to the target ions. Real-time on-body assessment of sweat is also performed, and our results indicate that calcium concentration increases with decreasing pH. This platform can be used in noninvasive continuous analysis of ionized calcium and pH in body fluids for disease diagnosis such as primary hyperparathyroidism and kidney stones. PMID- 27380447 TI - Three-dimensional printed miniaturized spectral system for collagen fluorescence lifetime measurements. AB - Various types of collagens, e.g., type I and III, represent the main load-bearing components in biological tissues. Their composition changes during processes such as wound healing and fibrosis. When excited by ultraviolet light, collagens exhibit autofluorescence distinguishable by their unique fluorescent lifetimes across a range of emission wavelengths. Here, we designed a miniaturized spectral lifetime detection system as a noninvasive probe for monitoring tissue collagen compositions. A sine-modulated LED illumination was applied to enable frequency domain fluorescence lifetime measurements under three wavelength bands, separated via a series of longpass dichroics at 387, 409, and 435 nm. We employed a lithography-based three-dimensional (3-D) printer with <50 MUm resolution to create a custom designed optomechanics in a handheld form factor. We examined the characteristics of the optomechanics with finite element modeling to simulate the effect of thermal (from LED) and mechanical (from handling) strain on the optical system. The geometry was further optimized with ray tracing to form the final 3-D printed structure. Using this device, the phase shift and demodulation of collagen types were measured, where the separate spectral bands enhanced the differentiation of their lifetimes. This system represents a low cost, handheld probe for clinical tissue monitoring applications. PMID- 27380448 TI - Combined effects of scattering and absorption on laser speckle contrast imaging. AB - Several variables may affect the local contrast values in laser speckle contrast imaging (LSCI), irrespective of relative motion. It has been suggested that the optical properties of the moving fluid and surrounding tissues can affect LSCI values. However, a detailed study of this has yet to be presented. In this work, we examined the combined effects of the reduced scattering and absorption coefficients on LSCI. This study employs fluid phantoms with different optical properties that were developed to mimic whole blood with varying hematocrit levels. These flow phantoms were imaged with an LSCI system developed for this study. The only variable parameter was the optical properties of the flowing fluid. A negative linear relationship was seen between the changes in contrast and changes in reduced scattering coefficient, absorption coefficient, and total attenuation coefficient. The change in contrast observed due to an increase in the scattering coefficient was greater than what was observed with an increase in the absorption coefficient. The results indicate that optical properties affect contrast values and that they should be considered in the interpretation of LSCI data. PMID- 27380449 TI - Shack-Hartmann-based objective straylight assessment of the human eye in an increased scattering angle range. AB - Objective measurement of straylight in the human eye with a Shack-Hartmann (SH) wavefront aberrometer is limited in imaging angle. We propose a measurement principle and a point spread function (PSF) reconstruction algorithm to overcome this limitation. In our optical setup, a variable stop replaces the stop conventionally used to suppress reflections and scatter in SH aberrometers. We record images with 21 diameters of the stop. From each SH image, the average intensity of the pupil is computed and normalized. The intensities represent integral values of the PSF. We reconstruct the PSF, which is the derivative of the intensities with respect to the visual angle. A modified Stiles Holladay approximation is fitted to the reconstructed PSF, resulting in a straylight parameter. A proof-of-principle study was carried out on eight healthy young volunteers. Scatter filters were positioned in front of the volunteers' eyes to simulate straylight. The straylight parameter was compared to the C-Quant measurements and the filter values. The PSF parameter shows strong correlation with the density of the filters and a linear relation to the C-Quant straylight parameter. Our measurement and reconstruction techniques allow for objective straylight analysis of visual angles up to 4 deg. PMID- 27380450 TI - Impacts of Hypervirulence Determinants on Clinical Features and Outcomes of Bacteremia Caused by Extended-Spectrum beta-Lactamase-Producing Klebsiella pneumoniae. AB - We investigated the implications of hypervirulence determinants on clinical features of 48 adult patients with bacteremia caused by extended-spectrum beta lactamase-producing Klebsiella pneumoniae. Isolates in the hypervirulence group included any of the following virulence determinants: K1/K2 capsule serotypes, hypermucoviscosity phenotype, rmpA gene, or rmpA2 gene. Nonhypervirulence group isolates were negative for all of the above virulence factors. In this study, all isolates used were non-K1/K2 strains. Statistically significant differences were observed in clinical features of patients between the two groups. The hypervirulent isolates (n = 19), including 11 isolates with the hypermucoviscosity phenotype, 15 with the rmpA gene, and 16 with the rmpA2 gene, were more commonly recovered from diabetic patients and mainly manifested as secondary bacteremia (such as pneumonia, urinary tract infections, or other localized infections). The nonhypervirulent isolates (n = 29) were more commonly recovered from patients after prolonged hospital stays (>30 days) and mostly manifested as primary bacteremia. The overall in-hospital mortality was 56.3%. Hazard ratio (HR) analysis revealed the following positive predictors for mortality: nosocomial infection, stay in an intensive care unit, no removal of the central venous catheter, Charlson comorbidity score, and APACHE II score (?15). The negative predictors were initial appropriate antibiotic therapy (HR 0.42) and urinary tract infection (HR 0.19). Charlson score was an independent confounder based on multivariate analysis (HR 1.43, 95% confidence interval 1.04 1.99). In conclusion, hypervirulence determinants played a role in causing secondary infections in diabetic patients; however, the presence of morbidity cofactors could themselves influence mortality, despite the absence of hypervirulence determinants. PMID- 27380451 TI - Effects of metformin treatment on blood leptin and ghrelin levels in patients with type 2 diabetes mellitus. AB - BACKGROUND: The aim of the present study was to conduct a meta-analysis of randomized controlled trials (RCTs) that investigated the effects of metformin on blood leptin and ghrelin levels in patients with type 2 diabetes mellitus (T2DM). METHODS: Literature searches were performed using MEDLINE, Cochrane Controlled Trials Registry, and ClinicalTrials.gov, and RCTs that investigated the effects of metformin on blood leptin and ghrelin levels in patients with T2DM were selected. Standardized mean differences (SMDs) and 95 % confidence intervals (CIs) were calculated. RESULTS: Twelve RCTs met the eligibility criteria and were included in the meta-analysis. There was no significant difference in blood leptin between the metformin and control groups (SMD 0.03; 95 % CI -0.35 %, 0.42 %; P = 0.86), although there was a significant difference in blood leptin levels between the metformin group and the group on oral antidiabetic drugs (OADs) other than metformin (SMD -0.39; 95 % CI -0.76 %, -0.01 %; P = 0.04). There were no significant differences in blood ghrelin levels. CONCLUSIONS: Metformin treatment was not associated with a decrease in blood leptin levels in patients with T2DM compared with levels in patients in the control group. Moreover, metformin treatment was not associated with increases in blood ghrelin levels compared with the control and other OADs groups. However, blood leptin levels were significantly lower in the metformin compared with the other OADs group. PMID- 27380452 TI - Site-Selective Chemoenzymatic Glycosylation of an HIV-1 Polypeptide Antigen with Two Distinct N-Glycans via an Orthogonal Protecting Group Strategy. AB - A convergent chemoenzymatic approach for sequential installation of different N glycans in a polypeptide is described. The method includes introduction of distinguishably protected GlcNAc-Asn building blocks during automated solid phase peptide synthesis (SPPS), followed by orthogonal deprotection of the GlcNAc primers and site-selective sequential extension of the sugar chains through glycosynthase-catalyzed transglycosylation reactions. It was observed that the protecting groups on one neighboring GlcNAc moiety have an impact on the substrate activity of another GlcNAc acceptor toward some endoglycosynthases in transglycosylation. The usefulness of this synthetic strategy was exemplified by an efficient synthesis of the glycopeptide neutralizing epitope of broadly HIV neutralizing antibody PG9. The method should be generally applicable for the synthesis of complex glycopeptides carrying multiple different N-glycans. PMID- 27380453 TI - Baby born too soon: an overview and the impact beyond the infection. AB - Spontaneous preterm delivery, prematurity, and low birth weight due to prematurity account for a great part of neonatal morbidity and mortality. Inflammation may cause preterm labor, with the involvement of different mediators that produce diverse aspects of the inflammatory response. Although bacteria are considered to be the main trigger for intrauterine infection/inflammation, immunological factors also appear to be involved. Recently, molecular genetic studies have helped us better understand the underlying pathophysiologic processes. During mammalian pregnancy, maternal-fetal tolerance involves a number of immunosuppressive factors produced by placenta. Recently, placenta-derived exosomes have emerged as new immune regulators in the maternal immune tolerance. This review focuses on the specific immune parameters that become altered during human pregnancy, the identity and function of some immune modulators that have been best characterized to date, as well as a comprehensive evaluation of the pregnancy-associated mechanisms that downregulate proinflammatory immunity to a level sufficient to prevent the triggering of premature common pathway of labor and damage to developing organs. PMID- 27380454 TI - Skin permeation of polycyclic aromatic hydrocarbons: A solvent-based in vitro approach to assess dermal exposures against benzo[a]pyrene and dibenzopyrenes. AB - Consumer products with high contents of polycyclic aromatic hydrocarbons (PAHs) were repeatedly identified by market surveillance authorities. Since several of the individual compounds have been identified as genotoxic carcinogens, there might be health risks associated with the usage of these items. It therefore becomes reasonable to argue to reduce PAH contents in consumer products to a level as low as possible. This study presents data on the migration of PAHs from consumer products into aqueous sweat simulant or aqueous ethanol and on its combined migration and penetration into human skin. Product specimens were either submerged in simulant, or placed directly on test skins in Franz cell chambers to simulate dermal contacts. Migration of hexacyclic dibenzopyrenes became detectable by using ethanolic simulant, but not in aqueous sweat simulant. Similarly, migration of the pentacyclic model carcinogen benzo[a]pyrene (B[a]P) into aqueous sweat simulant was significantly lower when compared with human skin or skin models. The results point to a gross underestimation (about two orders of magnitude) when using aqueous sweat simulant instead of human skin for assessing PAH migration. On the other side, the usage of 20% ethanol as simulant revealed good agreement to the actual exposure of human skin against B[a]P migrating out of contaminated products. Our results underline that aqueous sweat simulant is not suitable to study dermal migration of highly lipophilic compounds. PMID- 27380455 TI - Semiempirical Quantum-Chemical Orthogonalization-Corrected Methods: Benchmarks of Electronically Excited States. AB - The semiempirical orthogonalization-corrected OMx methods have recently been shown to perform well in extensive ground-state benchmarks. They can also be applied to the computation of electronically excited states when combined with a suitable multireference configuration interaction (MRCI) treatment. We report on a comprehensive evaluation of the performance of the OMx/MRCI methods for electronically excited states. The present benchmarks cover vertical excitation energies, excited-state equilibrium geometries (including an analysis of significant changes between ground- and excited-state geometries), minimum-energy conical intersections, ground- and excited-state zero-point vibrational energies, and 0-0 transition energies for a total of 520 molecular structures and 412 excited states. For comparison, we evaluate the TDDFT/B3LYP method for all benchmark sets, and the CC2, MRCISD, and CASPT2 methods for some of them. We find that the current OMx/MRCI methods perform reasonably well for many of the excited state properties. However, in comparison to the first-principles methods, there are also a number of shortcomings that should be addressed in future developments. PMID- 27380457 TI - Diagnostic Dilemma of Takotsubo Cardiomyopathy in the Setting of Decompensated Cirrhosis. PMID- 27380456 TI - Cytotoxic and Nitric Oxide Inhibition Activities of Propolis Extract along with Microencapsulation by Complex Coacervation. AB - In this study, cytotoxicity of ethanol extract of propolis (EEP) originating from Sivas, Turkey was screened against several cancer cell lines, namely PC-3, U87MG, A-549, mPANC96, CaCo-2, MCF-7, HeLa, MDA-MB-231 and a non-tumor cell line HEK293 by MTT assay. The inhibition levels of inducible nitric oxide synthase (iNOS) were also determined by using RAW 264.7 macrophage cells following lipopolysaccharide (LPS) treatment. EEP exhibited significant cytotoxic nitric oxide inhibition activities with an IC50 value of 0.1 +/- 0.1 MUg/ml indicating a high potential as an anti-inflammatory agent. In spite of these promising results and the fact that propolis is a highly nutritive substance, its low solubility and bitter taste limit the applications as a natural supplement. Encapsulation might serve as a good strategy in order to overcome these problems. Complex coacervation was applied where the main focus was on surfactant type, polymer ratio (alginate:gelatin), stirring rate and concentration of core material. The mean particle size of unloaded microparticles were 22.62 MUm obtained with gelatin:alginate ratio of 1:1 at a stirring rate of 1400 rpm with 2 ml of 1 % (w/v) sodium carboxymethyl cellulose (Na-CMC), whereas addition of EEP at a concentration of 100 mg/ml increased the mean particle size to 36.44 MUm and yielded an encapsulation efficiency of 98.77 %. The cytotoxicities of EEP loaded microparticles were also assessed both on MCF-7 and MDA-MB-231 where similar results were achieved as free EEP which can enhance the possible use of propolis extract in the industry as a natural supplement. PMID- 27380458 TI - Severe Elevation of Liver Enzymes Does Not Necessarily Require Treatment Interruption in Patients Treated With a Combination of Paritaprevir/Ritonavir/Ombitasvir Plus Dasabuvir for HCV Infection. PMID- 27380459 TI - Risk Factors for False Fecal Immunochemical Test Results in Colorectal Cancer Screening. AB - GOALS: We investigated the factors associated with false fecal immunochemical test (FIT) results for advanced colorectal neoplasm (ACRN). BACKGROUND: Data on whether certain subgroups of patients have an increased risk of inaccurate FIT results are extremely limited. STUDY: This was a retrospective study conducted in a university hospital in Korea from June 2013 to May 2015. Out of 34,547 participants who had an FIT completed, we analyzed a total of 3990 subjects aged 50 years and above who underwent colonoscopy. RESULTS: The rates of false negative and false-positive results were 58.0% and 15.7%, respectively. Elevated fasting blood glucose [adjusted odds ratio (AOR), 0.59; 95% confidence interval (CI), 0.36-0.97], the presence of high-grade dysplasia (AOR, 0.49; 95% CI, 0.25 0.95), 3 or more adenomas (AOR, 0.56; 95% CI, 0.35-0.89), cancer (AOR, 0.20; 95% CI, 0.11-0.38), and distal ACRN (AOR, 0.61; 95% CI, 0.39-0.96) were associated with a lower risk of false-negative FIT results. The presence of proximal ACRN (AOR, 1.59; 95% CI, 1.01-2.51) and adenoma >=10 mm (AOR, 4.38; 95% CI, 2.17-8.87) were associated with a higher risk of false-negative results. Older age (70 y and above; AOR, 1.67; 95% CI, 1.29-2.17), diverticulum (AOR, 1.94; 95% CI, 1.45 2.58), and hemorrhoid (AOR, 1.63; 95% CI, 1.32-2.01) were associated with false positive results. CONCLUSIONS: Subjects with a higher risk of false-negative results should be prioritized for earlier colonoscopy and subjects with inaccurate results should be more cautiously considered for screening by using modalities other than FIT. Our findings will contribute to individualization of screening programs. PMID- 27380460 TI - Older Patients With Hepatocellular Carcinoma Have More Advanced Disease, Lower Rates of Treatment, and Lower Survival. AB - GOALS: To evaluate age-specific disparities in cancer stage at diagnosis, receipt of treatment, and survival among adults with hepatocellular carcinoma (HCC). BACKGROUND: HCC has become the fastest rising cause of cancer-related deaths in the United States. The aging population coupled with the rising incidence of HCC will result in an emerging cohort of older patients with HCC placing significant burden health care systems. STUDY: Using 2003 to 2011 Surveillance, Epidemiology, and End Results data, a US population-based cancer registry, we retrospectively evaluated age-specific disparities in cancer stage at diagnosis, receipt of treatment, and survival among adults with HCC. Multivariate logistic regression models evaluated HCC stage at diagnosis and HCC treatment received. Multivariate Cox proportional hazard models evaluated long-term survival. RESULTS: Compared with HCC patients below 50 years old, patients aged 70 years or older were less likely to have HCC within Milan criteria [odds ratio, 0.58; confidence interval (CI), 0.54-0.63; P<0.001]. Older age was also associated with significantly lower rates of receiving HCC treatment. Even after adjusting for stage of disease, patients aged 70 years or older had the lowest odds of receiving any HCC treatment compared with patients below 50 years old (odds ratio, 0.52; CI, 0.46 0.60; P<0.001). On multivariate Cox regression, HCC patients aged 70 years or older had significantly lower survival compared with patients below 50 years old (hazards ratio, 1.22; CI, 1.15-1.30; P<0.001). CONCLUSIONS: Among US adults with HCC, patients aged 70 years or older were less likely to have HCC within Milan criteria at diagnosis, less likely to receive any HCC treatment, and had significantly lower long-term survival. PMID- 27380461 TI - Biomarkers of Hepatic Fibrosis in Chronic Hepatitis C: A Comparison of 10 Biomarkers Using 2 Different Assays for Hyaluronic Acid. AB - BACKGROUND: Advancing fibrosis is regarded as the most important factor when stratifying patients with chronic hepatitis C for retreatment. GOALS: (1) To compare the performance of 10 biomarkers of fibrosis, including patented tests, among patients with chronic hepatitis C and treatment failure; and (2) to assess the impact on biomarker performance of using 2 different assays of hyaluronic acid (HA). STUDY: For 80 patients, liver histology (Metavir) was compared with biomarker scores using sera obtained within 6 months of liver biopsy (indirect biomarkers: AST:ALT ratio, APRI, Forns index, FIB-4, Fibrometer V3G; direct biomarkers: ELF, Fibrospect II, Hyaluronic acid-HA, Fibrometer V2G, Hepascore). Direct biomarker scores were calculated using 2 validated assays for HA (ELISA and radiometric). RESULTS: Using the ELISA assay for HA to calculate the direct panels, all 10 of the biomarkers exhibited comparable overall discriminatory performance (unweighted Obuchowski measure, ordROC 0.92-0.94, P-value>0.05) except AST:ALT ratio and APRI (ordROC 0.86-0.88, P-value<0.05). For the detection of moderate (F2-4) and advanced (F3-4) fibrosis, the AUROC of Fibrometer 2G were significantly higher than AST:ALT ratio and APRI but none of the other biomarkers. Good correlation was observed between the 2 HA assays (intraclass correlation coefficient=0.873) with the ELISA assay exhibiting superior diagnostic performance (ordROC 0.92 vs. 0.88, P-value=0.003). Importantly, the performance of many of the direct biomarkers at their diagnostic thresholds was heavily influenced by the choice of HA assay. CONCLUSIONS: Although many biomarkers exhibited good diagnostic performance for the detection of advancing fibrosis, our results indicate that diagnostic performance may be significantly affected by the selection of individual component assays. PMID- 27380462 TI - Cyanoacrylate glue for gastrointestinal bleeding. AB - PURPOSE OF REVIEW: Cyanoacrylate (CYA) therapy has become an important component of the therapeutic toolbox of the interventional endoscopists with direct endoscopic injection accepted as first-line therapy of gastric varices. However, its generalized use has been cautioned by its serious adverse event profile. RECENT FINDINGS: Endoscopic ultrasound guided therapy has several conceptual advantages over free-hand injection, particularly as it ensures intravascular delivery of therapy. This has allowed innovation with the use of vascular coils with or without CYA therapy, and very encouraging long-term results are now published showing reduced serious adverse events and low rebleeding rates. SUMMARY: Direct endoscopic ultrasound guided intravascular injection of CYA is gaining widespread acceptance and offers reduced complication rates and significantly lower rebleeding rates. Data are supportive of CYA use both for primary and secondary prophylaxis of gastric varices. PMID- 27380463 TI - Genotype-Phenotype Association Study Reveals CFI-Rs13104777 to be a Protective Genetic Marker Against Acute Anterior Uveitis. AB - PURPOSE: To investigate the roles of CFI, genotype-phenotype associations were identified in AAU. METHODS: A case-control study was conducted in a total of 575 subjects consisting of 279 AAU patients and 296 healthy controls. Genotypic analyses were performed using Sequenom MassARRAY technology. Analyses were stratified to a series of clinical ophthalmic confounding factors. RESULTS: A lower frequency of the CFI-rs13104777 C allele was found in the AAU cohort compared with the controls, and, thus, was significantly associated with AAU pathogenesis (p = 0.041, OR = 0.712, 95% CI: 0.513-0.987). Stratified analysis also demonstrated the associations may differ depending on the HLA-B27 status and laterality status. CONCLUSIONS: This study has revealed a significant genetic role for CFI-rs13104777 in AAU. This influence may be dependent on human leukocyte antigen (HLA)-B27 and disease laterality. Overall, the results provide evidence for a pathogenic role for CFI in AAU and expand our knowledge on the genetic basis of AAU. PMID- 27380464 TI - Duration of Infant Protection Against Influenza Illness Conferred by Maternal Immunization: Secondary Analysis of a Randomized Clinical Trial. AB - IMPORTANCE: Influenza immunization of women during pregnancy protects the young infants against influenza illness. The duration of this protection remains unclear. OBJECTIVE: To evaluate the duration of infant protection conferred by maternal immunization and its association with transplacental antibody transfer. DESIGN, SETTING, AND PARTICIPANTS: Infants born to women who participated in a randomized, double-blind, placebo-controlled clinical trial in 2011 and 2012 on the safety, immunogenicity, and efficacy of trivalent inactivated influenza vaccine (IIV3) during pregnancy were followed up during the first 6 months of life for polymerase chain reaction (PCR)-confirmed influenza illness. In a secondary analysis of a subset of infants, hemagglutination inhibition (HAI) antibodies were measured. The study was performed at a single center in South Africa. The secondary analysis was performed in October 2014. EXPOSURE: Maternal immunization for influenza. MAIN OUTCOMES AND MEASURES: The vaccine's efficacy against PCR-confirmed influenza illness and the percentage of infants with HAI titers of 1:40 or more by age group. RESULTS: There were 1026 infants (47.2% female) born to IIV3 recipients and 1023 infants (47.3% female) born to placebo recipients who were included in the analysis of the vaccine's efficacy. The vaccine's efficacy against PCR-confirmed influenza illness was highest among infants 8 weeks of age or younger at 85.6% (95% CI, 38.3%-98.4%) and decreased with increasing age to 25.5% (95% CI, -67.9% to 67.8%) among infants 8 to 16 weeks of age and to 30.3% (95% CI, -154.9% to 82.6%) among infants 16 to 24 weeks of age. Similarly, in the IIV3 group, the percentage of infants with HAI titers of 1:40 or more to the influenza vaccine strains decreased from more than 56% in the first week of life to less than 40% at 16 weeks of age and less than 10.0% at 24 weeks of age. CONCLUSIONS AND RELEVANCE: Maternal immunization conferred protection against infection in the infants for a limited period during early life. The lack of protection beyond 8 weeks of age correlated with a decrease in maternally derived antibodies. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01306669. PMID- 27380465 TI - Chemical composition of the essential oil from the aerial parts of Ononis reclinata L. (Fabaceae) grown wild in Sicily. AB - In the present study, the chemical composition of the essential oil from aerial parts of Ononis reclinata L., a species not previously investigated, collected in Sicily was evaluated by GC and Gas chromatography-Mass spectrometry. The main components of O. reclinata were menthone (43.6%), isopimpinellin (38.4%) and pulegone (11.2%). The comparison with other studied oils of genus Ononis showed a peculiar and characteristic profile. PMID- 27380466 TI - A Non-bipartite Propensity Score Analysis of the Effects of Teacher-Student Relationships on Adolescent Problem and Prosocial Behavior. AB - Previous research suggests a link between the quality of teacher-student relationships and the students' behavioral outcomes; however, the observational nature of past studies makes it difficult to attribute a causal role to the quality of these relationships. In the current study, therefore, we used a propensity score analysis approach to evaluate whether students who were matched on their propensity to experience a given level of relationship quality but differed on their actual relationship quality diverged on their concurrent and subsequent problem and prosocial behavior. Student/self, teacher, and parent- (only waves 1-3) reported data from 8 waves of the Zurich Project on the Social Development of Children and Youths (z-proso), a longitudinal study of Swiss youth among a culturally diverse sample of 7- to 15-year-olds were utilized. The initial sample included 1483 (49.4 % female) students for whom information relevant for this study was available. The sample represented families from around 80 different countries, from across all the continents; with approximately 42 % of the female primary caregivers having been born in Switzerland. Following successful matching, we found that students who reported better relationships with their teachers and whose teachers reported better relationships with them evidenced fewer problem behaviors concurrently and up to 4 years later. There was also evidence for an analogous effect in predicting prosocial behavior. The implications of these findings are discussed in relation to prevention and intervention practices. PMID- 27380467 TI - Congruence of Parents' and Children's Perceptions of Parenting: A Meta-Analysis. AB - Parents and children often report different perspectives about parents' behaviors. Such lack of congruence is important because it may reflect problems in their relationship and may be associated with children's maladjustment. We conducted a systematic, quantitative review of parent-child agreement and discrepancy about parenting behaviors, and potential moderators (e.g., children's age, race, clinical status, family intactness) of the extent of mother-child and father-child congruence. The meta-analyses included 85 studies with 476 effect sizes of the degree of agreement and discrepancy in parent-child reports of three parenting behaviors: Acceptance, Psychological Control, and Behavioral Control assessed with one of the most widely-used measures of parenting-the Children's Report of Parental Behavior Inventory. Mother-child and father-child dyads exhibited significant but modest levels of agreement (r) across parenting constructs. The amount and direction of discrepancy (Hedges' g) varied by the parenting construct and parents' sex. Overall, parents' reports were more favorable than their children's report about the parents' behaviors. Significant associations were found between the magnitude of agreement/discrepancy and children's age, race, clinical status, and family intactness. Moderators differed by parenting construct, parents' sex, and type of effect size. Implications of these findings for researchers and clinicians are discussed and highlight the need for further research about the meaning of parent-child incongruence, its relation to children's psychopathology, and interventions for reducing it. PMID- 27380468 TI - Design and Synthesis of a Low Bandgap Small Molecule Acceptor for Efficient Polymer Solar Cells. AB - A novel non-fullerene acceptor, possessing a very low bandgap of 1.34 eV and a high-lying lowest unoccupied molecular orbital level of -3.95 eV, is designed and synthesized by introducing electron-donating alkoxy groups to the backbone of a conjugated small molecule. Impressive power conversion efficiencies of 8.4% and 10.7% are obtained for fabricated single and tandem polymer solar cells. PMID- 27380469 TI - Reining in the supersized Phase I cancer trial. PMID- 27380470 TI - Comparing models of contrast gain using psychophysical experiments. AB - In a wide variety of neural systems, neurons tuned to a primary dimension of interest often have responses that are modulated in a multiplicative manner by other features such as stimulus intensity or contrast. In this methodological study, we present a demonstration that it is possible to use psychophysical experiments to compare competing hypotheses of multiplicative gain modulation in a neural population, using the specific example of contrast gain modulation in orientation-tuned visual neurons. We demonstrate that fitting biologically interpretable models to psychophysical data yields physiologically accurate estimates of contrast tuning parameters and allows us to compare competing hypotheses of contrast tuning. We demonstrate a powerful methodology for comparing competing neural models using adaptively generated psychophysical stimuli and demonstrate that such stimuli can be highly effective for distinguishing qualitatively similar hypotheses. We relate our work to the growing body of literature that uses fits of neural models to behavioral data to gain insight into neural coding and suggest directions for future research. PMID- 27380471 TI - Difference magnitude is not measured by discrimination steps for order of point patterns. AB - We have shown in previous work that the perception of order in point patterns is consistent with an interval scale structure (Protonotarios, Baum, Johnston, Hunter, & Griffin, 2014). The psychophysical scaling method used relies on the confusion between stimuli with similar levels of order, and the resulting discrimination scale is expressed in just-noticeable differences (jnds). As with other perceptual dimensions, an interesting question is whether suprathreshold (perceptual) differences are consistent with distances between stimuli on the discrimination scale. To test that, we collected discrimination data, and data based on comparison of perceptual differences. The stimuli were jittered square lattices of dots, covering the range from total disorder (Poisson) to perfect order (square lattice), roughly equally spaced on the discrimination scale. Observers picked the most ordered pattern from a pair, and the pair of patterns with the greatest difference in order from two pairs. Although the judgments of perceptual difference were found to be consistent with an interval scale, like the discrimination judgments, no common interval scale that could predict both sets of data was possible. In particular, the midpattern of the perceptual scale is 11 jnds away from the ordered end, and 5 jnds from the disordered end of the discrimination scale. PMID- 27380472 TI - The Effect of Synovectomy in Total Knee Arthroplasty for Primary Osteoarthritis: A Meta-Analysis. AB - The objective of this study is to assess pain, function, and morbidity in patients undergoing synovectomy during primary total knee arthroplasty (TKA) for osteoarthritis (OA). A meta-analysis, which included randomized controlled trials comparing TKA with and without synovectomy for OA, was completed. The primary outcome was postoperative knee pain. Secondary outcomes included performance, perioperative complications, validated functional scores, operation length, and hospitalization length. A literature search produced 487 unique references, of which 3 randomized controlled trials were selected for inclusion. A total of 304 patients (354 knees) were included, with an average age of 67 years. Follow-up intervals between studies ranged from 26 weeks to 12 months. Included studies were of moderate- to high-quality evidence with low risk of bias. There was no significant difference between the two groups in regard to postoperative pain, Knee Society Score, or postoperative range of motion. Postoperative blood loss was significantly lower in synovium-retaining TKA group (MD = 99.41 mL; 95% confidence interval, 45.08-153.75). Based on these results, there is currently no evidence to support the use of synovectomy in TKA for primary OA, as it provides no clinical benefit and increases postoperative blood loss. PMID- 27380474 TI - Male meliponine bees (Scaptotrigona aff. depilis) produce alarm pheromones to which workers respond with fight and males with flight. AB - In highly social hymenopteran societies, males mainly serve reproductive purposes. Semiochemicals enable the different hymenopteran sexes and castes to communicate with each other and to coordinate important functions within colonies. I hereby show that sexual dimorphism in meliponine bees incorporates the alarm and defence communication system. I chemically analysed the mandibular glands of Scaptotrigona aff. depilis using GCMS methods and conducted behavioural experiments in both males and female workers using cephalic and mandibular gland extracts. In addition, behaviour studies with male cephalic extracts were also conducted in Scaptotrigona bipunctata and Partamona cupira. Males and female worker bees showed differences in the content of the mandibular glands, which are responsible for alarm communication in meliponines. Males never attacked but usually fled when confronted with the mandibular gland extract content of other conspecific males or females. Interestingly, however, meliponine males were still able to raise alarm and to induce substantial amounts of aggression at nest entrances, which is different from the much better known and studied honey bees. Potential reasons are briefly discussed. PMID- 27380473 TI - A new device for monitoring individual activity rhythms of honey bees reveals critical effects of the social environment on behavior. AB - Chronobiological studies of individual activity rhythms in social insects can be constrained by the artificial isolation of individuals from their social context. We present a new experimental set-up that simultaneously measures the temperature rhythm in a queen-less but brood raising mini colony and the walking activity rhythms of singly kept honey bees that have indirect social contact with it. Our approach enables monitoring of individual bees in the social context of a mini colony under controlled laboratory conditions. In a pilot experiment, we show that social contact with the mini colony improves the survival of monitored young individuals and affects locomotor activity patterns of young and old bees. When exposed to conflicting Zeitgebers consisting of a light-dark (LD) cycle that is phase-delayed with respect to the mini colony rhythm, rhythms of young and old bees are socially synchronized with the mini colony rhythm, whereas isolated bees synchronize to the LD cycle. We conclude that the social environment is a stronger Zeitgeber than the LD cycle and that our new experimental set-up is well suited for studying the mechanisms of social entrainment in honey bees. PMID- 27380475 TI - Antiphospholipid syndrome: analysis of dilute Russell's viper venom time titer. AB - To evaluate the characteristic features of the dilute Russell's viper venom time (DRVVT) titer in the antiphospholipid syndrome (APS). The medical record of 3660 consecutive patients with DRVVT orders between 2006 and 2015 were examined for criteria satisfying the diagnosis of APS. DRVVT titer was studied as a function of titer distribution, titer stability, and clinicopathologic features. Twenty six patients were diagnosed with APS based on a persistently positive DRVVT and a history of arterial or venous thrombosis. DRVVT titer was mostly of low magnitude (65-77% of patients), was of similar value between initial and repeat testing (mean DRVVT titer 1.40 vs. 1.38; P = 0.858; mean time interval 216 days), and was positively associated with anticardiolipin antibodies (IgG and IgM) and antibeta 2-glycoprotein I antibodies (IgG and IgM) (P < 0.020). Low titer and moderate/high titer DRVVT were associated with a triple positive antiphospholipid antibody profile in 0 and 62% of patients, respectively (P < 0.020). DRVVT titer in APS was predominantly low in magnitude, stable over time, and associated with specific antiphospholipid antibody profiles. PMID- 27380477 TI - The impact of disseminated intravascular coagulation on the outcome of cancer patients with venous thromboembolism: Erratum. PMID- 27380478 TI - Clinical efficiency in orthognathic surgical treatment. PMID- 27380479 TI - Methodological quality and outcome of systematic reviews reporting on orthopaedic treatment for Class III malocclusion: Overview of systematic reviews. PMID- 27380476 TI - Lupus anticoagulant-hypoprothrombinemia syndrome and catastrophic antiphospholipid syndrome in a patient with antidomain I antibodies. AB - Lupus anticoagulant-hypoprothrombinemia syndrome is a rare condition characterized by the association of acquired factor II deficiency and lupus anticoagulant. Contrary to classical antiphospholipid syndrome, it may cause severe life-threatening bleeding (89% of published cases). We report a patient, positive for antidomain I antibodies, with initially primary lupus anticoagulant hypoprothrombinemia syndrome without previous clinical manifestation or underlying systemic disease. Five years later, he experienced the first systemic lupus erythematous flare. Within a few days, catastrophic antiphospholipid syndrome was diagnosed with heart, liver and kidney involvement. The patient recovered under pulse steroids, intravenous heparin and intravenous immunoglobulins. PMID- 27380480 TI - Torque resistance of different stainless steel wires commonly used for fixed retainers in orthodontics. PMID- 27380481 TI - Orthodontic treatment need of 9-, 12-, and 15-year-old children according to the index of orthodontic treatment need and dental aesthetic index. PMID- 27380482 TI - Space closing versus space opening for bilateral missing upper laterals - Aesthetic judgements of laypeople: A web-based survey. PMID- 27380483 TI - Outcome of combined orthodontic-surgical treatment in a United Kingdom university dental institute. AB - INTRODUCTION: This retrospective observational cohort study evaluated effectiveness of combined orthodontic-orthognathic surgical treatment in a UK University Dental Institute. METHODS: Patients were identified from a database maintained prospectively throughout a 5-year period of observation. Demographic and clinical data included age, malocclusion, Index of Treatment Need, Index of Orthognathic Functional Treatment Need, orthodontist, surgeon, surgical procedure and treatment-time. Peer Assessment Rating (PAR) scores were generated from pre- and post-treatment dental study casts by a single calibrated examiner. RESULTS: One hundred and sixty two subjects began treatment during the period of observation, 92 completed, 14 elected to discontinue before surgery and 56 remained in treatment. Outcome data were available for 73, 16 males and 57 females (mean age 23.28 [SD, 7.92] years). Within this sample, 33 (45.2%) presented with class II division 1, 6 (8.2%) with class II division 2 and 34 (46.6%) with class III malocclusion. Isolated maxillary and mandibular surgery was carried out in 3 (4.1%) and 24 cases (32.8%), respectively; bimaxillary surgery was performed in 46 (63.1%). Mean total treatment time in fixed appliances was 920.28 days (30.7 months). Mean pre-treatment PAR score was 39.09 [SD, 9.42] and post-treatment 5.86 [SD, 4.25] with a mean 83.7% PAR score reduction, representing a greatly improved occlusal result. Kruskal-Wallis testing found no evidence of any relationship between independent variables and percentage PAR reduction; however, surgeon identity did significantly influence treatment length (P = 0.007). CONCLUSIONS: This investigation demonstrates that in terms of static occlusion combined orthodontic-orthognathic surgery is effective in correcting severe malocclusion. PMID- 27380488 TI - Handbook of Orthodontics 2nd Edition. PMID- 27380484 TI - Space closing versus space opening for bilateral missing upper laterals - aesthetic judgments of laypeople: a web-based survey. AB - OBJECTIVE: To investigate the opinions of laypeople regarding the aesthetic outcome of treating patients with developmental absence of both maxillary lateral incisors using either orthodontic space closure (OSC) or space opening and prosthetic replacement (PR). DESIGN: Cross sectional, web-based survey. METHODS: A panel of five orthodontists and five restorative dentists examined post treatment intra-oral images of 21 patients with developmental absence of both upper lateral incisors. A consensus view was obtained about the 10 most attractive images (5 OSC; 5 PR). The 10 selected images were used in a web-based survey involving staff and students at the University of Sheffield. In the first section, the participants were asked to evaluate the attractiveness of the 10 randomly arranged single images using a 5-point Likert scale. In the second section, an image of OSC was paired with an image of PR according to their attractiveness ranking by the clinician panel, and the participants were asked to indicate which of the two images they preferred. RESULTS: The survey received 959 completed responses with 9590 judgements. The images of OSC were perceived to be more attractive (mean rating 3.34 out of 5; SD 0.56) compared with the images of PR (mean rating 3.14 out of 5; SD 0.58) (mean diff 0.21; P < 0.001). Female and staff judges tended to give higher attractiveness ratings. Both females and males preferred the OSC images closing in 3 out of 4 paired images. CONCLUSION: Space closing was perceived to be more attractive than space opening by lay people. The findings have implications for advising patients about the best aesthetic outcome when both maxillary lateral incisors are missing. PMID- 27380489 TI - Turning Ineffective Transplatin into a Highly Potent Anticancer Drug via a Prodrug Strategy for Drug Delivery and Inhibiting Cisplatin Drug Resistance. AB - Clinically ineffective transplatin is highly potent against cancer cells when transformed into a transplatin(IV) prodrug nanoparticle. Herein, a hydrophobic transplatin(IV) was synthesized by H2O2-oxidization of transplatin and attachment of two hydrophobic aliphatic chains. Transplatin(IV) was subsequently encapsulated by a biodegradable amphiphilic copolymer, MPEG-PLA, forming a well defined spherical micelles (M(TransPt)). Transplatin(IV) was protected efficiently and could be released under a simulated cancerous intracellular condition. Compared to the cisplatin and transplatin, M(TransPt) showed the highest Pt uptake and a clathrin-dependent endocytosis pathway. Most importantly, M(TransPt) displayed a nanomolar IC50 on A2780 cells and a great potency on cisplatin resistant A2780DDP cell line. Overall, this nanoplatform for delivering trans-geometry platinum(IV) drug exhibits excellent characteristics for enhancing efficacy and overcoming cisplatin drug resistance, and holds a strong promise for clinical use in the near future. PMID- 27380490 TI - How Society Subsidizes Big Food and Poor Health. PMID- 27380491 TI - Novel phenanthridine (PHE-4i) derivative inhibits carrageenan-induced rat hind paw oedema through suppression of hydrogen sulfide. AB - This study was conducted to assess the anti-inflammatory effect of a novel synthesized phenanthridine alkaloid (PHE-4i) and to examine the possible involvement of hydrogen sulfide (H2S) in anti-inflammatory mechanism. The synthesized phenanthridine derivative PHE-4i (2, 5, and 10 mg/kg) was administered intraperitoneally to rats. One hour following treatment, inflammation was induced by intraplantar injection of carrageenan (1 %), in the hind paw. Paw volume as the index of inflammation was measured before and after carrageenan injection. Neutrophil sequestration into the hind paw was quantified by measuring tissue myeloperoxidase (MPO) activity and was compared for the inhibition of H2S production. Pretreatment with PHE-4i significantly reduced carrageenan-induced hind paw weight, MPO activity, leukocyte infiltration, and H2S production in a dose-dependent manner (p < 0.001). These results indicate that the anti-inflammatory effect of PHE-4i on carrageenan-induced rat paw oedema could be via the inhibition of the gaseous mediator H2S. PMID- 27380492 TI - Neurokinin-1 receptor inhibition reverses ischaemic brain injury and dementia in bilateral common carotid artery occluded rats: possible mechanisms. AB - BACKGROUNDS: Increase in SP release as a function of hypoxia of the rat carotid body is a tissue response to ischemia that leads to neurogenic inflammation and cognitive deficits. Substance P-mediated inflammation is reported to attenuate the neuroprotective PPAR-gamma. This study was undertaken to investigate the effect of aprepitant, a substance P-NK1 receptor antagonist in bilateral carotid artery occlusion (BCCAO)-induced ischaemic brain injury and vascular dementia. METHODS: Bilateral carotid artery occlusion was performed in Wistar rats to produce hypoperfusion and ischaemic injury. Dementia was noted by an increase in brain acetylcholinesterase (AChE) activity, and attenuation of learning ability (escape latency time) and memory retention (time spent in target quadrant) using Morris water maze. Oxidative stress was estimated by an increase in thiobarbituric acid reactive substances (TBARS) level and a decrease in reduced glutathione level. Vascular dysfunction was measured by attenuation of acetylcholine-induced endothelium-dependent relaxation (isolated carotid ring preparation), and increased in carotid artery TBARS level. Neurodegeneration was assessed in the hippocampus by H&E staining. Aprepitant and donepezil (positive control) were administered to rats from day 28 to day 42 after BCCAO. RESULTS: Aprepitant (20 and 40 mg/kg) and donepezil (2 mg/kg) significantly improved vascular function, learning and memory ability, and decreases the neuronal cell death, oxidative stress, and ache in BCCAO rats. Donepezil effect was more significant than the low dose of aprepitant on disease markers. However, BADGE (30 mg/kg a, PPAR-gamma antagonist) prevented the ameliorative effect of aprepitant. CONCLUSION: Thus, it may be concluded that aprepitant attenuates vascular dysfunction and dementia in BCCAO rats by activating downstream PPAR gamma. PMID- 27380493 TI - Fibrosis and coronary perfusion - a cardiovascular disease risk in an African male cohort: The SABPA study. AB - Low-grade inflammation has been correlated with risk factors of cardiovascular diseases (CVD). Whether the pro-inflammatory and thrombotic ratio (fibrosis) may contribute to CVD is not known. We therefore aimed to assess whether Cornell Product left ventricular hypertrophy (LVH) is associated with fibrosis and coronary perfusion (silent ischemia) in a bi-ethnic male cohort from South Africa. A cross sectional study was conducted including 165 African and Caucasian men between the ages of 20-65. Fasting blood samples were obtained to measure fibrinogen, C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor (TNF-alpha). Ambulatory blood pressure, ECG and 12 lead ECG measures were obtained to determine silent ischemic events (ST events) and LVH, respectively. Africans revealed more silent ischemia, higher 24 h blood pressure, inflammatory, coagulation as well as fibrosis levels than Caucasians. In a low-grade inflammatory state (CRP > 3 mg/l), Africans revealed higher fibrosis (p <= 0.01) values, but lower IL-6 and TNF-alpha values than Caucasians. Linear regression analyses in several models demonstrated positive associations between silent ischemia and fibrosis [Adj. R(2) 0.23; beta 0.35 (95% CI 0.13, 0.58), p <= 0.01]. In a low-grade inflammatory state (CRP>3mg/l), fibrinogen predicted AV-block in African men [OR 3.38 (95% CI 2.24, 4.53); p = 0.04]. Low-grade inflammation may induce AV-block through mechanisms involving fibrosis and ischemia to increase the burden on the heart in African men. PMID- 27380495 TI - Patiromer: A Review in Hyperkalaemia. AB - Patiromer (Veltassa(TM)) for oral suspension is a sodium-free potassium binder that is approved in the USA for the treatment of hyperkalaemia. In clinical trials, patiromer significantly reduced serum potassium levels from baseline to week 4 in patients with chronic kidney disease (CKD) and mild to severe hyperkalaemia (OPAL-HK), or CKD, mild to moderate hyperkalaemia and type 2 diabetes mellitus (AMETHYST-DN), who were receiving renin-angiotensin-aldosterone system inhibitors (RAASis; drugs that inhibit the renal excretion of potassium). Among patients in OPAL-HK who had moderate to severe hyperkalaemia at baseline and normokalaemia on patiromer and RAASis at week 4, continuing patiromer for a further 8 weeks maintained reductions in potassium levels more effectively than switching to placebo (i.e. withdrawing patiromer); consequently, fewer patiromer than placebo recipients experienced recurrent hyperkalaemia during this period. Furthermore, almost all patiromer (vs. less than half of placebo) recipients were still receiving RAASi therapy at the end of this trial. In AMETHYST-DN, the significant reduction from baseline in serum potassium levels seen at week 4 was sustained for up to 52 weeks. Patiromer was generally well tolerated in these trials, with no treatment-related serious adverse events or deaths. Commonly occurring treatment-related adverse events include mild to moderate constipation and hypomagnesaemia, and there is a low risk of hypokalaemia. In conclusion, oral patiromer is a useful new option for patients with hyperkalaemia. PMID- 27380494 TI - Long noncoding RNA GIHCG promotes hepatocellular carcinoma progression through epigenetically regulating miR-200b/a/429. AB - Long noncoding RNAs (lncRNAs) have been reported to play pivotal roles in a variety of cancers. However, lncRNAs involved in hepatocellular carcinoma (HCC) initiation and progression remain largely unclear. In this study, we identified an lncRNA gradually increased during hepatocarcinogenesis (lncRNA-GIHCG) using publicly available microarray data. Our results further revealed that GIHCG is upregulated in HCC tissues in comparison with adjacent non-tumor tissues. High GIHCG expression is correlated with large tumor size, microvascular invasion, advanced BCLC stage, and poor survival of HCC patients. Functional experiments showed that GIHCG promotes HCC cells proliferation, migration, and invasion in vitro, and promotes xenografts growth and metastasis in vivo. Mechanistically, we demonstrated that GIHCG physically associates with EZH2 and the promoter of miR 200b/a/429, recruits EZH2 and DNMT1 to the miR-200b/a/429 promoter regions, upregulates histone H3K27 trimethylation and DNA methylation levels on the miR 200b/a/429 promoter, and dramatically silences miR-200b/a/429 expression. Furthermore, the biological functions of GIHCG on HCC are dependent on the silencing of miR-200b/a/429. Collectively, our results demonstrated the roles and functional mechanisms of GIHCG in HCC, and indicated GIHCG may act as a prognostic biomarker and potential therapeutic target for HCC. KEY MESSAGE: lncRNA-GIHCG is upregulated in HCC and associated with poor survival of patients. GIHCG significantly promotes tumor growth and metastasis of HCC. GIHCG physically associates with EZH2. GIHCG upregulates H3K27me3 and DNA methylation levels on the miR-200b/a/429 promoter. GIHCG epigenetically silences miR-200b/a/429 expression. PMID- 27380496 TI - Immature platelet fraction predicts coagulopathy-related platelet consumption and mortality in patients with sepsis. AB - INTRODUCTION: The diagnostic and prognostic value of immature platelet fraction (IPF) in sepsis has not been determined. This study aimed to assess whether IPF is an early predictor of platelet decline due to coagulopathy and is associated with mortality in patients with sepsis. MATERIALS AND METHODS: In total, 149 patients with a platelet count of >=80*10(3)/MUL on intensive care unit admission (101 with sepsis, 48 controls without sepsis) were prospectively evaluated. We measured IPF on admission and observed for development of subsequent platelet count decline (defined as a >30% decrease or <80*10(3)/MUL) in 5days, and mortality at 28days. The absolute immature platelet count (AIPC) was calculated to evaluate thrombopoiesis. RESULTS: Forty-seven patients with sepsis subsequently developed a decrease in platelet count. The IPF was highest in patients whose platelet count decreased, followed by patients without a decrease in platelet count and controls (median, 4.3% [3.1%-8.1%] vs. 3.7% [2.6%-4.6%] vs. 2.1% [1.6%-3.5%], respectively; P<0.0001). The AIPC was similar in patients with and without a decrease in platelet count (7.6 [4.2-10.0] vs. 5.9 [4.2 8.7]*10(3)/MUL, respectively; P=0.32). Coagulation derangement was more severe in patients who did than did not subsequently develop a decreased platelet count. Cox regression and receiver operator characteristic curve analysis revealed that IPF was a strong independent predictor of mortality, with accuracy similar to a standard prognostic scoring system. CONCLUSIONS: The admission IPF in septic patients predicts a subsequent decrease in platelet count, indicating platelet consumption with ongoing coagulopathy and risk of poor prognosis. PMID- 27380497 TI - Through the eyes to memory: Fixation durations as an early indirect index of concealed knowledge. AB - In three experiments, we investigated an early memory effect in eye fixations, namely increased durations of the second fixations to known relative to unfamiliar stimuli. This effect occurs even if knowledge of the stimulus is deliberately concealed. In Experiment 1, we found the early memory effect using object materials and a gaze-contingent stimulus presentation that controlled for parafoveal stimulus processing. In Experiment 2a, we looked for the effect under conditions commonly used in the concealed information test (CIT). To this end, participants encoded the "to-be-concealed" knowledge incidentally while doing a mock crime task, which was followed by a CIT. Beyond the control of parafoveal stimulus processing in Experiment 1, this procedure allowed minimization of influences of carry-over processes associated with the preceding stimulus. Experiment 2b replicated Experiment 2a but applied a 1-week retention interval between the encoding of the to-be-concealed knowledge and the CIT. We observed an early memory effect in all experiments, suggesting that the effect is robust, irrespective of the paradigm, stimulus materials, and retention interval used. PMID- 27380498 TI - Practice makes imperfect: Working memory training can harm recognition memory performance. AB - There is a great deal of debate concerning the benefits of working memory (WM) training and whether that training can transfer to other tasks. Although a consistent finding is that WM training programs elicit a short-term near-transfer effect (i.e., improvement in WM skills), results are inconsistent when considering persistence of such improvement and far transfer effects. In this study, we compared three groups of participants: a group that received WM training, a group that received training on how to use a mental imagery memory strategy, and a control group that received no training. Although the WM training group improved on the trained task, their posttraining performance on nontrained WM tasks did not differ from that of the other two groups. In addition, although the imagery training group's performance on a recognition memory task increased after training, the WM training group's performance on the task decreased after training. Participants' descriptions of the strategies they used to remember the studied items indicated that WM training may lead people to adopt memory strategies that are less effective for other types of memory tasks. These results indicate that WM training may have unintended consequences for other types of memory performance. PMID- 27380499 TI - Do learners predict a shift from recency to primacy with delay? AB - The shift from recency to primacy with delay reflects a fundamental observation in the study of memory. As time passes, the accessibility of earlier-learned representations tends to increase relative to the accessibility of later-learned representations. In three experiments involving participants' memory for text materials, we examined whether participants understood that there might be such a shift with retention interval. In marked contrast to their actual performance, participants predicted recency effects at both shorter and longer retention intervals. Our findings add to the evidence that the storage and retrieval dynamics of the human memory system, though adaptive overall from a statistics-of use standpoint, are both complex and poorly understood by users of the system. PMID- 27380500 TI - Influence of mowing on dynamics of native phytoseiid mites and Tetranychus urticae in apple orchards in northern Japan. AB - To support practical integrated pest management in commercial apple orchards, I investigated the influence of mowing on the occurrence of Tetranychus urticae and native phytoseiid mites in apple orchards sprayed with selective insecticides in Akita Prefecture, northern Japan, from 2013 to 2015. The orchards were not mown in 2013, and unmown and mown plots were compared in 2014 and 2015. There were significantly fewer Typhlodromus vulgaris on apple leaves and Amblyseius tsugawai in the undergrowth in mown plots than in unmown plots in both years. Conversely, there were significantly more T. urticae on leaves and undergrowth in mown plots than in unmown plots. The reason for the decreased populations of these phytoseiid mites may be a lack of food (pollen) needed for reproduction on apple trees and in the undergrowth due to mowing. These results indicate that mowing strongly influences generalist phytoseiid mites in apple orchards. Moreover, mowing might increase the density of T. urticae in apple trees because increased nitrogen in the leaves increases fecundity; in addition, drought might promote the increase of mite numbers. Thus, retention of undergrowth suppresses T. urticae in apple orchards. PMID- 27380501 TI - Development of microsatellite markers for six Tetranychus species by transfer from Tetranychus urticae genome. AB - Microsatellite markers are frequently used to explore the population genetic structure of organisms. Spider mites (genus Tetranychus) are important agricultural pests. Several markers have been developed for T. urticae, but for other spider mites, few such markers are available, hampering studies of their population genetics. In this study, we developed and characterized microsatellite markers for six non-model spider mite species (T. truncatus, T. kanzawai, T. ludeni, T. piercei, T. phaselus and T. pueraricola) by cross-species amplification of markers in the T. urticae genome, in order to better understand the population structure of Tetranychus species. Among 228 screened loci, many were polymorphic, including 13 loci in T. urticae, 11 loci in T. truncatus, 15 loci in T. pueraricola, 23 loci in T. kanzawai, 19 loci in T. piercei, 11 loci in T. phaselus and 9 loci in T. ludeni. Sequence analysis determined that the fragment length variations of the transferred microsatellites were mainly due to the variations of the numbers of repeats. These new microsatellite markers should be useful for studying the population genetics of the seven Tetranychus species. PMID- 27380503 TI - Taking adolescent prescription opioid use in context: risk stratification in early mid-life based on medical and nonmedical use. PMID- 27380505 TI - Effects of load mass carried in a backpack upon respiratory muscle fatigue. AB - PURPOSE: The purpose of this study was to investigate whether loads carried in a backpack, with a load mass ranging from 0 to 20 kg, causes respiratory muscle fatigue. METHODS: Eight males performed four randomised load carriage (LC) trials comprising 60 min walking at 6.5 km h(-1) wearing a backpack of either 0 (LC0), 10 (LC10), 15 (LC15) or 20 kg (LC20). Inspiratory (PImax) and expiratory (PEmax) mouth pressures were assessed prior to and immediately following each trial. Pulmonary gas exchange, heart rate (HR), blood lactate and glucose concentration and perceptual responses were recorded during the first and final 60 s of each trial. RESULTS: Group mean PImax and PEmax were unchanged following 60-min load carriage in all conditions (p > .05). There was an increase over time in pulmonary gas exchange, HR and perceptions of effort relative to baseline measures during each trial (p < .05) with changes not different between trials (p > .05). CONCLUSIONS: These findings indicate that sub-maximal walking with no load or carrying 10, 15 or 20 kg in a backpack for up to 60 min does not cause respiratory muscle fatigue despite causing an increase in physiological, metabolic and perceptual parameters. PMID- 27380504 TI - Comparison of the efficiency of combined extracorporeal shock-wave therapy and triple therapy versus triple therapy itself in Category III B chronic pelvic pain syndrome (CPPS). AB - The aim of this study is to determine the effect of combining extracorporeal shock-wave therapy (ESWT) and triple therapy versus triple therapy alone, when treating Category III B chronic prostatitis (CPPS). Study included 60 patients, classified as having CPPS, divided into two groups: the first group numbered 30 patients, who were treated with a combination of an alpha-blocker, an anti inflammatory agent and a muscle relaxant; the second group consisted of 30 patients who received a combination of ESWT and the fore-mentioned triple therapy. Patients were treated for 12 weeks. The primary criterion of a response to therapy was scoring 2 or less on the NIH-CPSI quality of life item, while the secondary criterion of a response to therapy was a greater than a 50% reduction in NIH-CPSI pain score. Patients who received triple therapy did not show a significant change neither in post void residual urine (PVR) nor in maximum flow rate (QMAX), while the second group of patients exhibited significant improvement in both PVR and QMAX values. Both groups of patients showed statistically significant improvement in all items of the NIH-CPSI score after the treatment, with significantly better results in the second group. PMID- 27380502 TI - Transmission of risk from parents with chronic pain to offspring: an integrative conceptual model. AB - Offspring of parents with chronic pain are at increased risk for pain and adverse mental and physical health outcomes (Higgins et al, 2015). Although the association between chronic pain in parents and offspring has been established, few studies have addressed why or how this relation occurs. Identifying mechanisms for the transmission of risk that leads to the development of chronic pain in offspring is important for developing preventive interventions targeted to decrease risk for chronic pain and related outcomes (eg, disability and internalizing symptoms). This review presents a conceptual model for the intergenerational transmission of chronic pain from parents to offspring with the goal of setting an agenda for future research and the development of preventive interventions. Our proposed model highlights 5 potential mechanisms for the relation between parental chronic pain and pediatric chronic pain and related adverse outcomes: (1) genetics, (2) alterations in early neurobiological development, (3) pain-specific social learning, (4), general parenting and family health, and (5) exposure to stressful environment. In addition, the model presents 3 potential moderators for the relation between parent and child chronic pain: (1) the presence of chronic pain in a second parent, (2) timing, course, and location of parental chronic pain, and (3) offspring's characteristics (ie, sex, developmental stage, race or ethnicity, and temperament). Such a framework highlights chronic pain as inherently familial and intergenerational, opening up avenues for new models of intervention and prevention that can be family centered and include at-risk children. PMID- 27380507 TI - Suggestions on sarcopenia-related trials. PMID- 27380506 TI - Combining balneotherapy and health promotion to promote active and healthy ageing: the Balaruc-MACVIA-LR(r) approach. AB - Scaling up and replication of successful innovative integrated care models for chronic diseases is one of the targets of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). MACVIA-LR(r) (MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon) is a Reference Site of the EIP on AHA. The main objective of MACVIA-LR(r) is to develop innovative solutions in order to (1) improve the care of patients affected by chronic diseases, (2) reduce avoidable hospitalization and (3) scale up the innovation to regions of Europe. The MACVIA-LR(r) project also aims to assess all possible aspects of medicine-including non-pharmacologic approaches-in order to maintain health and prevent chronic diseases. These approaches include hydrotherapy and balneotherapy which can be of great importance if health promotion strategies are considered. Balneotherapy at Balaruc-les-Bains focusses on musculoskeletal diseases and chronic venous insufficiency of the lower limbs. Each year, over 46,000 people attend an 18-day course related to a new falls prevention initiative combining balneotherapy and education. On arrival, each person receives a flyer providing information on the risk of fall and, depending on this risk, a course is proposed combining education and physical activity. A pilot study assesses the impact of the course 6 and 12 months later. This health promotion strategy for active and healthy ageing follows the FEMTEC (World Federation of Hydrotherapy and Climatotherapy) concept. PMID- 27380508 TI - Changes in triglyceride, HDL-C, and non-HDL-C levels in patients with acute coronary syndrome. AB - BACKGROUND: Changes in high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels have been linked to residual cardiovascular risk, whereas non-HDL-C levels have been shown to be more predictive of cardiovascular risk than are low-density lipoprotein cholesterol (LDL-C) levels. We aimed to investigate the impact of HDL-C, TG, and non-HDL-C levels on acute coronary syndrome (ACS) risk with on-target LDL-C levels. METHODS: In all, 424 Caucasian patients aged over 50 years who had LDL-C levels below 3.4 mmol/l with a first or subsequent ACS event were enrolled in a multicenter, retrospective study. Lipid samples were collected within 4 days after the cardiovascular event. The subjects of the age-matched, gender-balanced control group (n = 443) had LDL-C levels below 3.4 mmol/l and were free of cardiovascular diseases. RESULTS: Patients with ACS had significantly higher TG and lower HDL-C levels compared with the control patients; however, we did not find any significant difference regarding non-HDL-C levels between the two groups. In regression analysis, the risk of coronary heart disease increased significantly with 1 standard deviation (SD) increase in TG and 1 SD decrease in HDL-C levels. CONCLUSION: High TG and low HDL-C levels may contribute to residual cardiovascular risk in patients with well-controlled LDL-C levels; however, non-HDL-C levels at admission did not seem to be predictive for patients with ACS. Detection and treatment of secondary lipid targets such as high TG and low HDL-C levels may be important for the prevention of cardiovascular diseases. PMID- 27380509 TI - The neutrophil-lymphocyte ratio as an inflammatory marker in acute exacerbation of COPD. PMID- 27380511 TI - Veranstaltungen. PMID- 27380510 TI - Orosomucoid is an independent predictor of prognosis in chronic heart failure. AB - BACKGROUND: Heart failure is associated with low-grade inflammation. In the present study we sought to assess the prognostic impact of orosomucoid, a marker of inflammation, in outpatients with heart failure. METHODS: In outpatients with chronic heart failure (no change in clinical status and/or therapy >3 months prior to inclusion), baseline levels of orosomucoid were determined. Clinical follow-up was obtained and the rate of heart failure-related deaths and hospitalisations recorded. RESULTS: A total of 134 patients (median age 71, 33.3 % female, mean left ventricular ejection fraction [LVEF] 36 %) were included. During a median follow-up of 695 (456-811) days, 54 patients (40.1 %) experienced an event. On Cox multivariate analysis, orosomucoid levels above the median (>497 mg/l) emerged as an independent predictor of prognosis (hazard ratio = 2.86, 95 % confidence interval 1.48-5.52 after adjusting for age, gender, ischaemic vs. non ischaemic aetiology, LVEF, NT-proBNP and NYHA class). CONCLUSION: Orosomucoid levels are an independent predictor of heart failure-related mortality and hospitalisations in patients with chronic heart failure. PMID- 27380512 TI - Cost analysis of whole genome sequencing in German clinical practice. AB - OBJECTIVES: Whole genome sequencing (WGS) is an emerging tool in clinical diagnostics. However, little has been said about its procedure costs, owing to a dearth of related cost studies. This study helps fill this research gap by analyzing the execution costs of WGS within the setting of German clinical practice. METHODOLOGY: First, to estimate costs, a sequencing process related to clinical practice was undertaken. Once relevant resources were identified, a quantification and monetary evaluation was conducted using data and information from expert interviews with clinical geneticists, and personnel at private enterprises and hospitals. This study focuses on identifying the costs associated with the standard sequencing process, and the procedure costs for a single WGS were analyzed on the basis of two sequencing platforms-namely, HiSeq 2500 and HiSeq Xten, both by Illumina, Inc. In addition, sensitivity analyses were performed to assess the influence of various uses of sequencing platforms and various coverage values on a fixed-cost degression. RESULTS: In the base case scenario-which features 80 % utilization and 30-times coverage-the cost of a single WGS analysis with the HiSeq 2500 was estimated at ?3858.06. The cost of sequencing materials was estimated at ?2848.08; related personnel costs of ?396.94 and acquisition/maintenance costs (?607.39) were also found. In comparison, the cost of sequencing that uses the latest technology (i.e., HiSeq Xten) was approximately 63 % cheaper, at ?1411.20. CONCLUSIONS: The estimated costs of WGS currently exceed the prediction of a 'US$1000 per genome', by more than a factor of 3.8. In particular, the material costs in themselves exceed this predicted cost. PMID- 27380513 TI - Childhood leukaemia near nuclear sites in Belgium, 2002-2008. AB - This paper describes an ecological study investigating whether there is an excess incidence of acute leukaemia among children aged 0-14 years living in the vicinity of the nuclear sites in Belgium. Poisson regression modelling was carried out for proximity areas of varying sizes. In addition, the hypothesis of a gradient in leukaemia incidence with increasing levels of surrogate exposures was explored by means of focused hypothesis tests and generalized additive models. For the surrogate exposures, three proxies were used, that is, residential proximity to the nuclear site, prevailing winds and simulated radioactive discharges, on the basis of mathematical dispersion modelling. No excess incidence of acute leukaemia was observed around the nuclear power plants of Doel or Tihange nor around the nuclear site of Fleurus, which is a major manufacturer of radioactive isotopes in Europe. Around the site of Mol-Dessel, however, two- to three-fold increased leukaemia incidence rates were found in children aged 0-14 years living in the 0-5, 0-10 and the 0-15 km proximity areas. For this site, there was evidence for a gradient in leukaemia incidence with increased proximity, prevailing winds and simulated radioactive discharges, suggesting a potential link with the site that needs further investigation. An increased incidence of acute leukaemia in children aged 0-14 years was observed around one nuclear site that hosted reprocessing activities in the past and where nuclear research activities and radioactive waste treatment are ongoing. PMID- 27380514 TI - Correction: A Computerized Test of Design Fluency. AB - [This corrects the article DOI: 10.1371/journal.pone.0153952.]. PMID- 27380515 TI - Detecting Causality by Combined Use of Multiple Methods: Climate and Brain Examples. AB - Identifying causal relations from time series is the first step to understanding the behavior of complex systems. Although many methods have been proposed, few papers have applied multiple methods together to detect causal relations based on time series generated from coupled nonlinear systems with some unobserved parts. Here we propose the combined use of three methods and a majority vote to infer causality under such circumstances. Two of these methods are proposed here for the first time, and all of the three methods can be applied even if the underlying dynamics is nonlinear and there are hidden common causes. We test our methods with coupled logistic maps, coupled Rossler models, and coupled Lorenz models. In addition, we show from ice core data how the causal relations among the temperature, the CH4 level, and the CO2 level in the atmosphere changed in the last 800,000 years, a conclusion also supported by irregularly sampled data analysis. Moreover, these methods show how three regions of the brain interact with each other during the visually cued, two-choice arm reaching task. Especially, we demonstrate that this is due to bottom up influences at the beginning of the task, while there exist mutual influences between the posterior medial prefrontal cortex and the presupplementary motor area. Based on our results, we conclude that identifying causality with an appropriate ensemble of multiple methods ensures the validity of the obtained results more firmly. PMID- 27380517 TI - [Not Available]. PMID- 27380518 TI - [Not Available]. PMID- 27380519 TI - [Not Available]. PMID- 27380516 TI - Nonlinear Network Reconstruction from Gene Expression Data Using Marginal Dependencies Measured by DCOL. AB - Reconstruction of networks from high-throughput expression data is an important tool to identify new regulatory relations. Given that nonlinear and complex relations exist between biological units, methods that can utilize nonlinear dependencies may yield insights that are not provided by methods using linear associations alone. We have previously developed a distance to measure predictive nonlinear relations, the Distance based on Conditional Ordered List (DCOL), which is sensitive and computationally efficient on large matrices. In this study, we explore the utility of DCOL in the reconstruction of networks, by combining it with local false discovery rate (lfdr)-based inference. We demonstrate in simulations that the new method named nlnet is effective in recovering hidden nonlinear modules. We also demonstrate its utility using a single cell RNA seq dataset. The method is available as an R package at https://cran.r project.org/web/packages/nlnet. PMID- 27380520 TI - [Not Available]. PMID- 27380521 TI - Homologs of the LapD-LapG c-di-GMP Effector System Control Biofilm Formation by Bordetella bronchiseptica. AB - Biofilm formation is important for infection by many pathogens. Bordetella bronchiseptica causes respiratory tract infections in mammals and forms biofilm structures in nasal epithelium of infected mice. We previously demonstrated that cyclic di-GMP is involved in biofilm formation in B. bronchiseptica. In the present work, based on their previously reported function in Pseudomonas fluorescens, we identified three genes in the B. bronchiseptica genome likely involved in c-di-GMP-dependent biofilm formation: brtA, lapD and lapG. Genetic analysis confirmed a role for BrtA, LapD and LapG in biofilm formation using microtiter plate assays, as well as scanning electron and fluorescent microscopy to analyze the phenotypes of mutants lacking these proteins. In vitro and in vivo studies showed that the protease LapG of B. bronchiseptica cleaves the N-terminal domain of BrtA, as well as the LapA protein of P. fluorescens, indicating functional conservation between these species. Furthermore, while BrtA and LapG appear to have little or no impact on colonization in a mouse model of infection, a B. bronchiseptica strain lacking the LapG protease has a significantly higher rate of inducing a severe disease outcome compared to the wild type. These findings support a role for c-di-GMP acting through BrtA/LapD/LapG to modulate biofilm formation, as well as impact pathogenesis, by B. bronchiseptica. PMID- 27380522 TI - Morus alba L. Stem Extract Attenuates Pain and Articular Cartilage Damage in the Anterior Cruciate Ligament Transection-Induced Rat Model of Osteoarthritis. AB - AIM: This study was designed to investigate the anti-nociceptive effect of Morus alba stem extract as well as its cartilage protective effect in the anterior cruciate ligament transection (ACLT)-induced rat model of osteoarthritis (OA). METHODS: The anti-nociceptive effect of this plant extract was determined by measuring hind limb weight bearing, while the severity of cartilage damage to the knee joints was evaluated using the modified Mankin grading system. RESULTS: Oral administration of M. alba stem extract (56 and 560 mg/kg) significantly attenuated joint pain as indicated by a significant (p < 0.05) increase in the values of percent weight borne on the operated hind limb for the OA-induced groups that received M. alba stem extract at 56 and 560 mg/kg when compared to those of the vehicle-treated OA-induced group. In addition, a significant improvement in the Mankin score was also observed in rats treated with 560 mg/kg M. alba stem extract, which was in agreement with its pain-relieving effect. CONCLUSION: The results showed that M. alba stem extract exhibited an anti nociceptive effect as well as cartilage protection in the ACLT-induced rat model of OA, supporting its potential use as a therapeutic treatment for OA. PMID- 27380523 TI - Hydrogen Bonding to Hexafluoroisopropanol Controls the Oxidative Strength of Hypervalent Iodine Reagents. AB - Hexafluoroisopropan-2-ol (HFIP) has been found to be an unusually beneficial solvent for undertaking hypervalent iodine-initiated [2+2] cycloaddition of styrenes. For the initiator phenyliodine(III) diacetate (PIDA), voltammetric data demonstrate that the enhanced reactivity in HFIP is due to its greater oxidizing abilities in this fluorinated solvent such that in HFIP the reactivity of PIDA is comparable if not superior to its fluorinated analog phenyliodine(III) bis(trifluoroacetate). These results contrast with the often reported view that the role of the fluoroalcohol is to stabilize a radical cation formed by single electron transfer. Moreover, combined NMR and HRMS results reveal the formation of a strong H-bonded adduct between the solvent and oxidizing reagent which is the physical origin of the observed altered synthetic reactivity. PMID- 27380524 TI - In situ Immobilization of Copper Nanoparticles on Polydopamine Coated Graphene Oxide for H2O2 Determination. AB - Nanostructured electrochemical sensors often suffer from irreversible aggregation and poor adhesion to the supporting materials, resulting in reduced sensitivity and selectivity over time. We describe a versatile method for fabrication of a H2O2 sensor by immobilizing copper nanoparticles (Cu NPs; 20 nm) on graphene oxide (GO) sheets via in-situ reduction of copper(II) on a polydopamine (PDA) coating on a glassy carbon electrode. The PDA film with its amino groups and catechol groups acts as both a reductant and an adhesive that warrants tight bonding between the Cu NPs and the support. The modified electrode, best operated at a working voltage of -0.4 V (vs. Ag/AgCl), has a linear response to H2O2 in the 5 MUM to 12 mM concentration range, a sensitivity of 141.54 MUA?mM?1?cm?2, a response time of 4 s, and a 1.4 MUM detection limit (at an S/N ratio of 3). The sensor is highly reproducible and selective (with minimal interference to ascorbic acid and uric acid). The method was applied to the determination of H2O2 in sterilant by the standard addition method and gave recoveries between 97% and 99%. PMID- 27380526 TI - Fingerprints of Calcium-Binding Protein Conformational Dynamics Monitored by Surface Plasmon Resonance. AB - Surface plasmon resonance (SPR) spectroscopy is widely used to probe interactions involving biological macromolecules by detecting changes in the refractive index in a metal/dielectric interface following the dynamic formation of a molecular complex. In past years, SPR-based experimental approaches were developed to monitor conformational changes induced by the binding of small analytes to proteins coupled to the surface of commercially available sensor chips. A significant contribution to our understanding of the phenomenon came from the study of several Ca(2+)-sensor proteins operating in diverse cellular scenarios, in which the conformational switch is triggered by specific Ca(2+) signals. Structural and physicochemical analyses demonstrated that the SPR signal not only depends on the change in protein size upon Ca(2+)-binding but likely originates from variations in the hydration shell structure. The resulting changes in the dielectric properties of water or of the protein-water interface eventually reflect different crowding conditions on the SPR sensor chip, which mimic the cellular environment. SPR could hence be used to monitor conformational transitions in proteins, especially when a significant variation in the hydrophobicity of the solvent-exposed protein surface occurs, thus leading to changes in the dielectric milieu of the whole sensor chip surface. We review recent work in which SPR has been successfully employed to provide a fingerprint of the conformational change dynamics in proteins under native and altered conditions, which include post-translational modifications, copresence of competing analytes, and point mutations of single amino acids associated with genetic diseases. PMID- 27380525 TI - HRP2 and pLDH-Based Rapid Diagnostic Tests, Expert Microscopy, and PCR for Detection of Malaria Infection during Pregnancy and at Delivery in Areas of Varied Transmission: A Prospective Cohort Study in Burkina Faso and Uganda. AB - BACKGROUND: Intermittent screening and treatment (IST) of malaria during pregnancy has been proposed as an alternative to intermittent preventive treatment in pregnancy (IPTp), where IPTp is failing due to drug resistance. However, the antenatal parasitaemias are frequently very low, and the most appropriate screening test for IST has not been defined. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a multi-center prospective study of 990 HIV-uninfected women attending ANC in two different malaria transmission settings at Tororo District Hospital, eastern Uganda and Colsama Health Center in western Burkina Faso. Women were enrolled in the study in the second or third trimester of pregnancy and followed to delivery, generating 2,597 blood samples for analysis. Screening tests included rapid diagnostic tests (RDTs) targeting histidine-rich protein 2 (HRP2) and parasite lactate dehydrogenase (pLDH) and microscopy, compared to nPCR as a reference standard. At enrolment, the proportion of pregnant women who were positive for P. falciparum by HRP2/pan pLDH RDT, Pf pLDH/pan pLDH RDT, microscopy and PCR was 38%, 29%, 36% and 44% in Uganda and 21%, 16%, 15% and 35% in Burkina Faso, respectively. All test positivity rates declined during follow-up. In comparison to PCR, the sensitivity of the HRP2/pan pLDH RDT, Pf pLDH/pan pLDH RDT and microscopy was 75.7%, 60.1% and 69.7% in Uganda, 55.8%, 42.6% and 55.8% in Burkina Faso respectively for all antenatal visits. Specificity was greater than 96% for all three tests. Comparison of accuracy using generalized estimating equation revealed that the HRP2- detecting RDT was the most accurate test in both settings. CONCLUSIONS/SIGNIFICANCE: The study suggests that HRP2-based RDTs are the most appropriate point-of-care test currently available for use during pregnancy especially for symptomatic women, but will still miss some PCR-positive women. The clinical significance of these very low density infections needs to be better defined. PMID- 27380527 TI - Inhibition by Tranilast of the Synergistic Induction of Degranulation and IL-13 Expression by IL-33 and FcERI Cross-linking in Mast Cells. AB - PURPOSE: To assess the effects of tranilast on degranulation and IL-13 production in mast cells activated by IL-33 and cross-linking of FcERI. METHODS: Bone marrow derived mast cells (BMMCs) were sensitized with anti-DNP IgE. Sensitized cells were pretreated with tranilast and further stimulated with DNP-BSA, IL-33, or a combination of DNP-BSA and IL-33. Degranulation and the level of IL-13 release and mRNA expression in BMMCs were measured. RESULTS: Simultaneous stimulation with DNP-BSA and IL-33 resulted in marked increase in beta-hexosaminidase release. Tranilast significantly inhibited degranulation of BMMCs in the condition of combined treatment of DNP-BSA and IL-33. Combination of DNP-BSA and IL-33 induced a pronounced increase in the IL-13 release and mRNA expression. Tranilast significantly inhibited IL-13 release and mRNA expression in BMMCs stimulated by DNP-BSA and IL-33. CONCLUSIONS: Tranilast has efficacy on the inhibition of degranulation and IL-13 production in BMMCs induced by the combination of DNP-BSA and IL-33. PMID- 27380528 TI - Association of Heart Rate with N-Terminal Pro-B-Type Natriuretic Peptide in Septic Patients: A Prospective Observational Cohort Study. AB - BACKGROUND: Excessive sympathetic stress has multiple adverse effects during critical illness including sepsis. Recent studies showed that heart rate control had a significant effect on reducing mortality in septic shock patients. Furthermore, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in septic patients were reportedly associated with adverse outcome. However, no study has evaluated the relationship between hemodynamic profiles of septic patients and the circulating cardiac biomarker. Our objective was to determine whether hemodynamic profiles, specifically tachycardia and new-onset atrial fibrillation (AF), were associated with NT-proBNP elevation in septic patients. METHODS: We consecutively enrolled patients admitted to our intensive care unit (ICU). NT-proBNP levels, heart rate, and rhythm at ICU admission were measured, and all clinical and laboratory data were prospectively collected. Tachycardia was defined as a heart rate of above 100 bpm. RESULTS: Ninety-five patients out of 267 patients (35.6%) were diagnosed as sepsis. Of these septic patients, 47 presented with tachycardia and 6 developed new-onset AF. Multivariate Cox regression analysis revealed that tachycardia was an independent predictor of 28-day overall survival in septic patients (hazard ratio, 4.22; 95% confidence interval, 1.10-27.72; P < 0.05), but not in nonseptic patients. Multivariate linear regression analysis demonstrated that the presence of tachycardia was an independent determinant of NT-proBNP elevation (P < 0.05) in septic patients, but not in nonseptic patients. CONCLUSIONS: Tachycardia was significantly and independently associated with NT-proBNP elevation and lower survival rate in septic patients, although no association was observed in nonseptic patients. Increased NT-proBNP in sepsis with tachycardia might predict poor outcomes in ICU. PMID- 27380529 TI - What If I Don't Have Blood? Hextend is Superior to 3% Saline in an Experimental Model of Far Forward Resuscitation After Hemorrhage. AB - INTRODUCTION: Hypertonic crystalloid solutions, colloids, and fresh whole blood (FWB) have all been proposed for prehospital resuscitation after hemorrhage. However, there are no direct comparisons of the efficacy of these different fluids. We compared Hextend, 3% hypertonic saline (HS), and FWB in a porcine model of hemorrhagic shock. MATERIALS AND METHODS: Female swine (n = 5/group) underwent splenectomy and pressure-controlled hemorrhage followed by resuscitation with Hextend, 3% HS, or FWB. They were maintained at a target mean arterial pressure (MAP) for 4 h, holding or infusing fluid as necessary. Sham animals for comparison underwent splenectomy alone. RESULTS: The mean volume required to maintain target MAP was significantly higher for 3% HS (1,016 +/- 386 mL) than for Hextend (346 +/- 299 mL, P < 0.05). After 4 h of resuscitation, the MAP in the 3% HS group (44 +/- 3 mmHg) was significantly lower than shams (56 +/- 7 mmHg, P < 0.05). Three percent HS recipients had a significantly worse metabolic acidosis and anemia than shams or FWB recipients, as well as significant increases in serum sodium and chloride. Serum interleukin-6 was significantly elevated in 3% HS and FWB recipients relative to Hextend recipients (105.3 +/- 58.6 and 97.2 +/- 21 vs. 38.6 +/- 27.1 pcg/mL, P < 0.05). CONCLUSIONS: HS performed inferiorly to Hextend as a volume expanding resuscitative fluid after hemorrhage. On the basis of our data, we would recommend the use of Hextend over 3% saline in far forward resuscitation after hemorrhage. PMID- 27380530 TI - Propranolol Reduces Cardiac Index But does not Adversely Affect Peripheral Perfusion in Severely Burned Children. AB - PURPOSE: The aim of this study was to quantify the effect of propranolol on hemodynamic parameters assessed using the PiCCO system in burned children. METHODS: We analyzed hemodynamic data from patients who were randomized to receive either propranolol (4 mg/kg/day) or placebo (control), which was initiated as a prospective randomized controlled trial. Endpoints were cardiac index (CI), percent predicted heart rate (%HR), mean arterial pressure (MAP), percent predicted stroke volume (%SV), rate pressure product (RPP), cardiac work (CW), systemic vascular resistance index (SVRI), extravascular lung water index (EVLWI), arterial blood gases, events of lactic acidosis, and mortality. Mixed multiple linear regressions were applied, and a 95% level of confidence was assumed. RESULTS: One hundred twenty-one burned children (control: n = 62, propranolol: n = 59) were analyzed. Groups were comparable in demographics, EVLWI, SVRI, %SV, arterial blood gases, Denver 2 postinjury organ failure score, incidence of lactic acidosis, or mortality. Percent predicted HR, MAP, CI, CW, and RPP were significantly reduced in the propranolol-treated group (P <0.01). CONCLUSIONS: Propranolol significantly reduces cardiogenic stress by reducing CI and MAP in children with severe burn injury. However, peripheral oxygen delivery was not reduced and events of lactic acidosis as well as organ dysfunction was not higher in propranolol treated patients. PMID- 27380531 TI - Impact of Isolated Burns on Major Organs: A Large Animal Model Characterized. AB - Severe burn results in systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction (MOD). Currently, large-animal models of burn-induced SIRS/MOD mostly use secondary insults resulting in a paucity of knowledge on the effect of burn alone on different organ systems. The objective of the current study was to develop and characterize a large animal model of burn-induced SIRS over the course of 2 weeks. Yorkshire swine (n = 16) were randomized to sham controls (n = 4) or 40% total body surface area contact burns (n = 6 at 2 and 14 days post-burn). Blood chemistry and complete blood count analyses were performed at baseline and post-burn days 1, 2, 3, 7, 10, and 14. Upon euthanasia, tissue samples were taken for histopathology. Burns were found to be full thickness and did not re-epithelialize. SIRS was evidenced by increased body temperature, respiration rate, pulse, and white blood cell count for the duration of the experiment. Both acute liver injury and acute kidney injury were induced as determined biochemically and histologically. Histology also revealed atelectasis of the lungs which was associated with increased myeloperoxidase activity. Intestinal structure as well as enterocyte homeostasis was also disrupted. All of these organ abnormalities recovered to varying degrees by 14 days post-burn. We report a unique reproducible large animal model of burn-induced SIRS that can be tailored to specific organ systems for investigation into potential immunomodulatory interventions that prevent organ failure or promote organ recovery after burn injury. PMID- 27380532 TI - Previous Cryopreservation Alters the Natural History of the Red Blood Cell Storage Lesion. AB - BACKGROUND: During storage, packed red blood cells (pRBCs) undergo a number of biochemical, metabolic, and morphologic changes, collectively known as the "storage lesion." We aimed to determine the effect of cryopreservation on the red blood cell storage lesion compared with traditional 4 degrees C storage. METHODS: Previously cryopreserved human pRBCs were compared with age-matched never-frozen pRBCs obtained from the local blood bank. The development of the red cell storage lesion was evaluated after 7, 14, 21, 28, and 42 days of storage at 4 degrees C in AS-3 storage medium. We measured physiological parameters including cell counts, lactic acid, and potassium concentrations as well as signs of eryptosis including loss of phosphatidylserine (PS) asymmetry, microparticle production, and osmotic fragility in hypotonic saline. RESULTS: Compared with controls, previously cryopreserved pRBC at 7 days of storage in AS-3 showed lower red cell counts (3.7 vs. 5.3 * 10 cells/MUL, P < 0.01), hemoglobin (Hgb) (12.0 vs. 16.5 g/dL, P < 0.01), hematocrit (33.0% vs. 46.5%, P < 0.01), and pH (6.27 vs. 6.72, P < 0.01). Over 28 days of storage, storage cryopreserved pRBC developed increased cell-free Hgb (0.7 vs. 0.3 g/dL, P < 0.01), greater PS exposure (10.1% vs. 3.3%, P < 0.01), and microparticle production (30,836 vs. 1,802 MP/MUL, P < 0.01). Previously cryopreserved cells were also less resistant to osmotic stress. CONCLUSION: The red blood cell storage lesion is accelerated in previously cryopreserved pRBC after thawing. Biochemical deterioration of thawed and deglycerolized red cells suggests that storage time before transfusion should be limited to achieve similar risk profiles as never-frozen standard liquid storage pRBC units. PMID- 27380534 TI - The Role and Use of Estrogens Following Trauma. AB - Several lines of evidence indicate that female sex is a protective factor in trauma and hemorrhage. In both clinical and experimental studies, proestrus females have been shown to have better chances of survival and reduced rates of posttraumatic sepsis. Estrogen receptors are expressed in a variety of tissues and exert genomic, as well as nongenomic effects. By improving cardiac, pulmonary, hepatic, and immune function, estrogens have been shown to prolong survival in animal models of hemorrhagic shock. Despite encouraging results from experimental studies, retrospective clinical studies have not clearly pointed to advantages of estrogens following trauma-hemorrhage, which may be due to insufficient study design. Therefore, this review aims to give an overview on the current evidence and emphasizes on the importance of further clinical investigation on estrogens following trauma. PMID- 27380533 TI - Zymosan-Induced Peritonitis: Effects on Cardiac Function, Temperature Regulation, Translocation of Bacteria, and Role of Dectin-1. AB - Zymosan-induced peritonitis is a model commonly used to study systemic inflammatory response syndrome and multiple organ dysfunction syndrome. However, effects of zymosan on cardiac function have not been reported. We evaluated cardiac responses to zymosan in mice and the role of beta-glucan and dectin-1 in mediating these responses. Temperature and cardiac function were evaluated before and after intraperitoneal (i.p.) injection of zymosan (100 or 500 mg/kg) or saline. Chronotropic and dromotropic functions were measured using electrocardiograms (ECGs) collected from conscious mice. Cardiac inotropic function was determined by echocardiography. High-dose zymosan caused a rapid and maintained hypothermia along with visual signs of illness. Baseline heart rate (HR) was unaffected but HR variability (HRV) increased, and there was a modest slowing of ventricular conduction. High-dose zymosan also caused prominent decreases in cardiac contractility at 4 and 24 h. Because zymosan is known to cause gastrointestinal tract pathology, peritoneal wash and blood samples were evaluated for bacteria at 24 h after zymosan or saline injection. Translocation of bacterial occurred in all zymosan-treated mice (n = 3), and two had bacteremia. Purified beta-glucan (50 and 125 mg/kg, i.p.) had no effect on temperature or ECG parameters. However, deletion of dectin-1 modified the ECG responses to high-dose zymosan; slowing of ventricular conduction and the increase in HRV were eliminated but a marked bradycardia appeared at 24 h after zymosan treatment. Zymosan-treated dectin-1 knockout mice also showed hypothermia and visual signs of illness. Fecal samples from dectin-1 knockout mice contained more bacteria than wild types, but zymosan caused less translocation of bacteria. Collectively, these findings demonstrate that zymosan-induced systemic inflammation causes cardiac dysfunction in mice. The data suggest that dectin-1 dependent and -independent mechanisms are involved. Although zymosan treatment causes translocation of bacteria, this effect does not have a major role in the overall systemic response to zymosan. PMID- 27380535 TI - Blood Lactate Levels Cutoff and Mortality Prediction in Sepsis-Time for a Reappraisal? a Retrospective Cohort Study. AB - The objective of this study was to identify the initial value of blood lactate that best correlates with 28-day mortality in resuscitated septic shock patients. This was a retrospective cohort study including 443 patients admitted to an intensive care unit (ICU) with severe sepsis or septic shock from the emergency department. A receiver-operating characteristic (ROC) curve was drawn to obtain the best cutoff value for initial blood lactate associated with 28-day mortality. Patients were then dichotomized according to the chosen lactate cutoff, and sensitivity, specificity, and positive and negative predictive values were calculated. Baseline blood lactate level more than 2.5 mmol/L showed the largest area under the ROC curve to predict 28-day mortality (ROC area, 0.70; 95% confidence interval [CI], 0.62-0.79), with sensitivity, specificity, and negative predictive value of 67.4%, 61.7%, and 94.2%, respectively. Mortality at 28 days was 16.9% (31/183) in patients with initial lactate more than 2.5 mmol/L and 5.8% (15/260) in patients with initial lactate at most 2.5 mmol/L (relative risk, 2.93; 95% CI, 1.63-5.28; P < 0.001). Initial blood lactate levels more than 2.5 mmol/L (hazard ratio [HR], 2.86; 95% CI, 1.53-5.33; P = 0.001) and Sepsis-related Organ Failure Assessment score at ICU admission (HR, 1.18; 95% CI, 1.09-1.27; P < 0.001) were associated with increased 28-day mortality in the adjusted Cox regression. In this retrospective cohort study, a lactate level more than 2.5 mmol/L was the best threshold to predict 28-day mortality among severe sepsis and septic shock patients. Further prospective studies should address the impact on morbidity and mortality of this threshold as a trigger to resuscitation in this population of critically ill patients. PMID- 27380536 TI - Plasma Transfusion: History, Current Realities, and Novel Improvements. AB - Traumatic hemorrhage is the leading cause of preventable death after trauma. Early transfusion of plasma and balanced transfusion have been shown to optimize survival, mitigate the acute coagulopathy of trauma, and restore the endothelial glycocalyx. There are a myriad of plasma formulations available worldwide, including fresh frozen plasma, thawed plasma, liquid plasma, plasma frozen within 24 h, and lyophilized plasma (LP). Significant equipoise exists in the literature regarding the optimal plasma formulation. LP is a freeze-dried formulation that was originally developed in the 1930s and used by the American and British military in World War II. It was subsequently discontinued due to risk of disease transmission from pooled donors. Recently, there has been a significant amount of research focusing on optimizing reconstitution of LP. Findings show that sterile water buffered with ascorbic acid results in decreased blood loss with suppression of systemic inflammation. We are now beginning to realize the creation of a plasma-derived formulation that rapidly produces the associated benefits without logistical or safety constraints. This review will highlight the history of plasma, detail the various types of plasma formulations currently available, their pathophysiological effects, impacts of storage on coagulation factors in vitro and in vivo, novel concepts, and future directions. PMID- 27380537 TI - How Often Does Stapedectomy for Otosclerosis Result in Endolymphatic Hydrops? AB - OBJECTIVES: 1) To evaluate the long-term (>=10 year) clinical incidence of endolymphatic hydrops (EH) after stapedectomy for otosclerosis, using low frequency sensorineural hearing loss (LFSNHL) as a marker for EH. 2) To determine the histologic incidence of EH in human temporal bone specimens (TBS) with a history of stapedectomy for otosclerosis. 3) To determine the histologic incidence of EH in a control group of human TBS. STUDY DESIGN: Retrospective review and temporal bone study. SETTING: Tertiary medical center and temporal bone pathology laboratory. PATIENTS: Patients with otosclerosis, human TBS with otosclerosis, and human TBS with presbycusis as the control group. INTERVENTION: Pure-tone audiometry, temporal bone pathology. MAIN OUTCOME MEASURES: 1) LFSNHL, defined as >10 decibel elevation of bone conduction thresholds at 250 and 500 Hz, after correcting for age-related hearing loss (per ISO 7029). 2) Histologic assessment of EH. RESULTS: In patients with otosclerosis, 8 of 110 (7.3%) operated patients versus 3 of 123 (2.4%) nonoperated patients developed LFSNHL (p = 0.08). No patients with LFSNHL had other symptoms of EH. In TBS with otosclerosis, 11 of 93 (11.8%) operated TBS versus 3 of 156 (1.9%) nonoperated TBS had evidence of EH (p <0.001). In the control group of TBS with presbycusis, 9 of 253 (3.5%) had EH. CONCLUSION: The long-term incidence of LFSNHL, a marker for EH, in patients with otosclerosis was not significantly higher in those who underwent stapedectomy. The histologic incidence of EH, however, was significantly higher in TBS that had undergone stapedectomy compared with nonoperated TBS or a control group of TBS. PMID- 27380538 TI - Modification of Osseointegrated Device Parameters to Improve Speech in Noise and Localization Ability: Clinical Recommendations. AB - OBJECTIVE: To determine how best to modify osseointegrated (OI) devices or environmental settings to maximize hearing performance. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENTS: Fourteen adults with single-sided deafness (SSD) with a minimum of 6 months OI usage and nine bilaterally normal hearing controls INTERVENTIONS: : Speech in noise (SIN) and localization ability were assessed in a multi-speaker array (R-Space) with patients repeating sentences embedded in competing noise and verbally indicating the source speaker, respectively. MAIN OUTCOME MEASURES: SIN and localization were assessed with multiple OI microphone settings-fixed-directional, omnidirectional, and adaptive-as well as an unaided (OI off) condition. Participants completed the Abbreviated Profile of Hearing Aid Benefit questionnaire. RESULTS: Localization performance remains compromised for OI users with a high number of front-back confusions, but rapid learning using the fixed directional microphone setting improved localization of sounds on the device side despite poorer localization of sounds on the normal-hearing side. SIN performance is greatly enhanced with speech presented to the contra hearing ear rather than the OI device side. Subjective report of hearing ability is highly predictive of objective SIN measures. CONCLUSIONS: Clinicians should consider implementing a fixed-directional microphone setting for improved localization for sounds behind the OI device, but inform patients of the trade-off in performance on the normal hearing side. For better hearing in noise, clinicians should counsel OI recipients to orient the speech signal to their normal hearing ear rather than their OI device. The background noise subscale of the abbreviated profile of hearing aid benefit (APHAB) provides a meaningful metric by which to assess SIN performance of OI device users. PMID- 27380539 TI - Promoting Active Species Generation by Plasmon-Induced Hot-Electron Excitation for Efficient Electrocatalytic Oxygen Evolution. AB - Water splitting represents a promising technology for renewable energy conversion and storage, but it is greatly hindered by the kinetically sluggish oxygen evolution reaction (OER). Here, using Au-nanoparticle-decorated Ni(OH)2 nanosheets [Ni(OH)2-Au] as catalysts, we demonstrate that the photon-induced surface plasmon resonance (SPR) excitation on Au nanoparticles could significantly activate the OER catalysis, specifically achieving a more than 4 fold enhanced activity and meanwhile affording a markedly decreased overpotential of 270 mV at the current density of 10 mA cm(-2) and a small Tafel slope of 35 mV dec(-1) (no iR-correction), which is much better than those of the benchmark IrO2 and RuO2, as well as most Ni-based OER catalysts reported to date. The synergy of the enhanced generation of Ni(III/IV) active species and the improved charge transfer, both induced by hot-electron excitation on Au nanoparticles, is proposed to account for such a markedly increased activity. The SPR-enhanced OER catalysis could also be observed over cobalt oxide (CoO)-Au and iron oxy hydroxide (FeOOH)-Au catalysts, suggesting the generality of this strategy. These findings highlight the possibility of activating OER catalysis by plasmonic excitation and could open new avenues toward the design of more-energy-efficient catalytic water oxidation systems with the assistance of light energy. PMID- 27380540 TI - Safety and Efficacy of Siponimod (BAF312) in Patients With Relapsing-Remitting Multiple Sclerosis: Dose-Blinded, Randomized Extension of the Phase 2 BOLD Study. AB - IMPORTANCE: This dose-blinded extension of the phase 2 BOLD (BAF312 on MRI Lesion Given Once Daily) Study in relapsing-remitting multiple sclerosis provides evidence on disease activity and safety of a range of siponimod doses for up to 24 months. OBJECTIVE: To assess the safety and efficacy of siponimod for up to 24 months during the dose-blinded extension of the BOLD Study. DESIGN, SETTING, AND PARTICIPANTS: At extension baseline in a randomized clinical trial, patients taking siponimod continued at the originally assigned dose and patients taking placebo were rerandomized to the 5 siponimod doses. Initial treatment was titrated over 10 days. A total of 252 eligible patients were treated at specialized multiple sclerosis centers for this study conducted from August 30, 2010, through June 3, 2013. INTERVENTIONS: Siponimod at 10-mg, 2-mg, 1.25-mg, 0.5 mg, and 0.25-mg doses. MAIN OUTCOMES AND MEASURES: Safety assessment included blood tests, documentation of adverse events at regular scheduled visits and Holter monitoring; key efficacy measures were annualized relapse rate and magnetic resonance imaging lesion activity. RESULTS: Among the 252 eligible patients, the mean (SD) ages were 37.2 (8.4) years, 35.2 (9.1) years, 34.0 (7.6) years, 35.1 (9.2) years, and 36.8 (9.1) years in the 0.25-mg, 0.5-mg, 1.25-mg, 2 mg, and 10-mg groups. Of the 252 patients, 184 (73%) entered the extension and received siponimod (10 mg: n = 33; 2 mg: n = 29; 1.25 mg: n = 43; 0.5 mg: n = 29; and 0.25 mg: n = 50); 159 (86.4%) completed the dose-blinded extension. The incidence of adverse events was similar across treatment groups (10 mg: 87.9%; 2 mg: 89.7%; 1.25 mg: 88.4%; 0.5 mg: 96.6%; and 0.25 mg: 84.0%). Nine patients reported serious adverse events (2 mg: 3/29 [10.3%], 1.25 mg: 1/43 [2.3%], 0.5 mg: 4/29 [13.8%], and 0.25 mg: 1/50 [2.0%]; no serious adverse event was reported for more than 1 patient and no new safety signals occurred compared with the BOLD Study. Dose titration mitigated symptomatic bradycardic events. Reductions in mean (95% CI) gadolinium-enhancing T1 lesion counts from the last BOLD assessment were sustained in the 10-mg, 2-mg, 1.25-mg, and 0.5-mg dose groups (0 [0-0], 0.1 [0-1.9], 0.1 [0-2.6], and 0.1 [0-2.8] at month 24, respectively). At the 3 highest vs 2 lowest doses, the estimated new/newly enlarging T2 lesion counts (95% CIs) were lower during months 6 to 12 (0.5 [0.2-1.3], 0.4 [0.2-1.1], and 0.2 [0.1-0.6] vs 1.3 [0.6-2.8] and 1.4 [0.7-2.7]), months 12 to 18 (0.4 [0.1-1.1], 0.4 [0.1-1.3], and 0.4 [0.2-1.0] vs 1.0 [0.4-2.6] and 3.6 [1.7-7.6]), and months 18 to 24 (0 [0-not estimable], 0.9 [0.1-7.6], and 0.1 [0-1.7] vs 1.6 [0.3-7.7] and 2.0 [0.4-9.5]). Annualized relapse rates (95% CIs) up to month 24 were similarly lower for the 3 highest doses: 0.22 (0.12-0.40) for 10 mg, 0.20 (0.10 0.38) for 2 mg, and 0.14 (0.08-0.26) for 1.25 mg vs 0.33 (0.19-0.56) for 0.5 mg and 0.33 (0.21-0.50) for 0.25 mg. CONCLUSIONS AND RELEVANCE: For up to 24 months of siponimod treatment, multiple sclerosis disease activity was low and there were no new safety signals; investigation in phase 3 trials is encouraged. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01185821. PMID- 27380541 TI - Viewing the Valence Electronic Structure of Ferric and Ferrous Hexacyanide in Solution from the Fe and Cyanide Perspectives. AB - The valence-excited states of ferric and ferrous hexacyanide ions in aqueous solution were mapped by resonant inelastic X-ray scattering (RIXS) at the Fe L2,3 and N K edges. Probing of both the central Fe and the ligand N atoms enabled identification of the metal- and ligand-centered excited states, as well as ligand-to-metal and metal-to-ligand charge-transfer excited states. Ab initio calculations utilizing the RASPT2 method were used to simulate the Fe L2,3-edge RIXS spectra and enabled quantification of the covalencies of both occupied and empty orbitals of pi and sigma symmetry. We found that pi back-donation in the ferric complex is smaller than that in the ferrous complex. This is evidenced by the relative amounts of Fe 3d character in the nominally 2pi CN(-) molecular orbital of 7% and 9% in ferric and ferrous hexacyanide, respectively. Utilizing the direct sensitivity of Fe L3-edge RIXS to the Fe 3d character in the occupied molecular orbitals, we also found that the donation interactions are dominated by sigma bonding. The latter was found to be stronger in the ferric complex, with an Fe 3d contribution to the nominally 5sigma CN(-) molecular orbitals of 29% compared to 20% in the ferrous complex. These results are consistent with the notion that a higher charge at the central metal atom increases donation and decreases back-donation. PMID- 27380542 TI - Hyperthermia of magnetic nanoparticles allows passage of sodium fluorescein and Evans blue dye across the blood-retinal barrier. AB - PURPOSE: The blood-retina barrier (BRB) is a biological barrier consisting of tightly interconnected endothelial cells inside the retinal vascular network that protects the neural tissue from harmful pathogens and neurotoxic molecules circulating in the bloodstream. Unfortunately, with regard to retinoblastoma, this barrier also prevents systemically administered therapeutics reaching the retinal tissue. In this study we introduce a novel technique to locally and transiently increase BRB permeability for drug delivery using hyperthermia of magnetic nanoparticles (MNPs). MATERIALS AND METHODS: An alternating current (AC) magnetic field was used to induce hyperthermia of locally injected MNPs in the left ophthalmic artery of a rat model. To improve adherence on the surface of the endothelium, commercially available MNPs coated with human transferrin glycoproteins were used. After hyperthermia we assessed the extravasation of systemically injected sodium fluorescein (NaF) as well as Evans blue dye (EBD) into the retinal tissue. RESULTS: Spectrofluorometry and fluorescent microscopy image analysis show a significant increase of dye penetration in the retina where hyperthermia of MNPs was applied. CONCLUSIONS: Our proposed new technique can allow both small and large dye molecules to cross the BRB. While the results are preliminary and thorough evaluation of the retinal tissue following hyperthermia is necessary, this technique has the potential to be an effective mean for the treatment of various diseases such as retinoblastoma. PMID- 27380543 TI - Steatotic hepatocellular carcinoma: a variant associated with metabolic factors and late tumour relapse. AB - AIMS: Steatosis in hepatocellular carcinoma (HCC) has been recognized for decades and found most commonly in small, well-differentiated HCC. However, the clinicopathological features and pathogenesis of HCC with steatosis is not well characterized. There are few data concerning whether HCC with steatosis should be regarded a distinct histological variant, steatotic HCC. METHODS AND RESULTS: A retrospective cohort of 516 patients undergoing curative surgery for primary HCC was recruited. The median follow-up was 45.5 (range: 0.2-166.0) months. Steatotic HCC was defined as HCC with significant steatosis (>=5% of tumour cells). Associations with immunohistochemical expression of fatty acid binding protein-1 (FABP1), sonic hedgehog (SHH) and gene polymorphism of patatin-like phospholipase 3 (PNPLA3) were analysed. Steatotic HCC was found in 21.1% of patients and was associated with higher metabolic risks [diabetes mellitus (36.7% versus 18.2%) and hypertension (44.0% versus 28.7%)], underlying fatty liver (60.6% versus 37.8%), steatohepatitis (30.3% versus 13.0%), smaller tumour size, lower frequency of major vessel (1.8% versus 11.3%) and microvascular invasion (20.2% versus 32.4%), earlier tumour stages and lower serum alpha-fetoprotein. It was associated with developing late tumour relapse (hazard ratio 2.15, P = 0.002) independently of underlying cirrhosis and non-anatomical excision. Steatotic HCC did not differ from HCC without significant steatosis in immunohistochemical expression of FABP1 and SHH and PNPLA3 gene polymorphism. CONCLUSION: Steatotic HCC is a common histological variant of HCC with distinct association with underlying fatty liver, steatohepatitis and metabolic risks. Despite more favourable baseline tumour features, it was associated with late tumour relapse. PMID- 27380545 TI - tDCS combined with optokinetic drift reduces egocentric neglect in severely impaired post-acute patients. AB - Visuospatial neglect is a disabling syndrome resulting in impaired activities of daily living and in longer durations of inpatient rehabilitation. Effective interventions to remediate neglect are still needed. The combination of tDCS and an optokinetic task might qualify as a treatment method. A total of 32 post-acute patients with left (n = 20) or right-sided neglect were allotted to an intervention or a control group (both groups n = 16). The intervention group received eight sessions of 1.5-2.0 mA parietal transcranial direct current stimulation (tDCS) during the performance of an optokinetic task distributed over two weeks. Additionally they received standard therapy for five hours per day. The control group received only the standard therapy. Patients were examined twice before (with 3-4 days between examinations) and twice after treatment (5-6 days between examinations). Compared to the control group and controlling for spontaneous remission, the intervention group improved on spontaneous body orientation and the Clock Drawing Test. Intragroup comparisons showed broad improvements on egocentric but not on allocentric symptoms only for the intervention group. A short additional application of tDCS during an optokinetic task led to improvements of severe neglect compared to a standard neurological early rehabilitation treatment. Improvements seem to concern primarily egocentric rather than allocentric neglect. PMID- 27380546 TI - Improvements in the Crestal Osteotome Approach Have Decreased the Need for the Lateral Window Approach to Augment the Maxilla. AB - The use of the crestal approach to augment vertical height of the posterior maxilla for dental implant placement is reviewed in this article. The review of the literature documents the success of using a procedure that has minimal complications associated with it when performed correctly. An algorithmic approach is presented to guide surgeons on using the crestal osteotome approach for posterior maxillary augmentation. PMID- 27380547 TI - Bifunctional Organo/Metal Cooperatively Catalyzed [3 + 2] Annulation of para Quinone Methides with Vinylcyclopropanes: Approach to Spiro[4.5]deca-6,9-diene-8 ones. AB - A novel [3 + 2] annulation between para-quinone methides and vinylcyclopropanes for the synthesis of spiro[4.5]deca-6,9-diene-8-ones has been described. The palladium and phosphine-thiourea cooperative catalysis system played an important role in high yields and diastereoselectivities. The reaction exhibited good functional group tolerance and scalability. PMID- 27380548 TI - All Subdomains of the Talin Rod Are Mechanically Vulnerable and May Contribute To Cellular Mechanosensing. AB - Although the relevance of mechanotransduction in cell signaling is currently appreciated, the mechanisms that drive this process remain largely unknown. Mechanical unfolding of proteins may trigger distinct downstream signals in cells, providing a mechanism for cellular mechanotransduction. Force-induced unfolding of talin, a prominent focal adhesion protein, has been demonstrated previously for a small portion of its rod domain. Here, using single-molecule atomic force microscopy (smAFM), we show that the entire talin rod can be unfolded by mechanical extension, over a physiological range of forces between 10 and 40 pN. We also demonstrate, through a combination of smAFM and steered molecular dynamics, that the different bundles within the talin rod exhibit a distinct hierarchy of mechanical stability. These results provide a mechanism by which different force conditions within the cell control a graduated unfolding of the talin rod. Mechanical unfolding of the rod subdomains, and the subsequent effect on talin's binding interactions, would allow for a finely tuned cellular response to internally or externally applied forces. PMID- 27380549 TI - Providencia stuartii Isolates from Greece: Co-Carriage of Cephalosporin (blaSHV 5, blaVEB-1), Carbapenem (blaVIM-1), and Aminoglycoside (rmtB) Resistance Determinants by a Multidrug-Resistant Outbreak Clone. AB - Providencia stuartii has emerged as an important nosocomial pathogen. We describe an outbreak due to a multidrug-resistant strain over a 4-month period in a critical care unit in Athens. Molecular typing revealed each of the isolates to be clonally related with coresistance to cephalosporins, carbapenems, aminoglycosides, and quinolones. Each isolate contained a 220-kb multi-replicon (IncA/C and IncR) conjugative plasmid encoding TEM-1, SHV-5, VEB-1, and VIM-1 beta-lactamases and the 16S rDNA methylase RmtB. Antimicrobial therapy was unsuccessful in 3 of 6 cases, and resistance was readily transmissible to susceptible strains of Escherichia coli by transformation and conjugation. This highlights the clinical importance of P. stuartii and its ability to disseminate critical resistance determinants to other bacterial pathogens. PMID- 27380551 TI - Asymmetric Synthesis of Fused Polycyclic Indazoles through Aminocatalyzed Aza Michael Addition/Intramolecular Cyclization. AB - The first example of an asymmetric aminocatalyzed aza-Michael addition of 1H indazole derivatives to alpha,beta-unsaturated aldehydes is described. The iminium/enamine cascade process lies at the heart of our strategy, leading to enantioenriched fused polycyclic indazole architectures. Variations on both the alpha,beta-unsaturated aldehydes and the indazole-7-carbaldehyde heterocycles were studied in order to broaden the scope of the transformation in synthetically interesting directions. The fused polycyclic indazoles exhibit fluorescence properties and can undergo synthetic transformations. PMID- 27380550 TI - Assessment of flukicide efficacy against Fasciola hepatica in sheep in Sweden in the absence of a standardised test. AB - Anthelmintic resistance (AR) to Fasciola hepatica is emerging worldwide. Recently, AR to the adulticide compound albendazole (ABZ) was shown in Argentina and Spain. In Sweden, ABZ treatment failure against F. hepatica was first reported in sheep in 2012. The present study tested the efficacy of ABZ and triclabendazole (TCBZ) in sheep naturally infected with F. hepatica using a combination of three different diagnostic methods: faecal egg counts (FEC), coproantigen ELISA (cELISA) and Fasciola egg hatch test (FEHT). Two deworming trials, in November 2014 and January 2015, were performed on two sheep farms (farms A and B) in south-western Sweden. Except ABZ in November, treatment with ABZ or TCBZ achieved sufficient efficacy (97-100%) against adult F. hepatica on farm A. In contrast, ABZ treatment failed in the sheep flock on farm B, despite low initial faecal egg output. On farm B, ABZ efficacy based on FEC was 67% (95% CI: 35-84) and four of eight ewes tested were coproantigen-positive 21 days post treatment. Ovicidal activity of ABZ against Fasciola eggs in isolates from both farms and one additional bovine isolate were tested by FEHT to exclude the presence of juvenile flukes and other factors such as dosing failure and poor quality of drug product. Irrespective of drug trial, data from FEHT showed significantly lower ovicidal activity of ABZ for the ovine farm B isolate than for the isolate from farm A. This confirms that the low efficacy of ABZ in sheep flock B was associated with ABZ resistance. Overall, the usefulness of three complementary methods for detection of ABZ resistance in the field was demonstrated. PMID- 27380552 TI - Multiplex Detection of IgG and IgM to Rift Valley Fever Virus Nucleoprotein, Nonstructural Proteins, and Glycoprotein in Ovine and Bovine. AB - A multiplex fluorescence microsphere immunoassay (FMIA) was used to detect bovine and ovine IgM and IgG antibodies to several Rift Valley fever virus (RVFV) proteins, including the major surface glycoprotein, Gn; the nonstructural proteins, NSs and NSm; and the nucleoprotein, N. Target antigens were assembled into a multiplex and tested in serum samples from infected wild-type RVFV or MP12, a modified live virus vaccine. As expected, the N protein was immunodominant and the best target for early detection of infection. Antibody activity against the other targets was also detected. The experimental results demonstrate the capabilities of FMIA for the detection of antibodies to RVFV structural and nonstructural proteins, which can be applied to future development and validation of diagnostic tests that can be used to differentiate vaccinated from infected animals. PMID- 27380553 TI - Chiral Sensing of Various Amino Acids Using Induced Circularly Polarized Luminescence from Europium(III) Complexes of Phenanthroline Dicarboxylic Acid Derivatives. AB - Circularly polarized luminescence (CPL) was observed from [Eu(dppda)2 ](-) (dppda=4,7-diphenyl-1,10-phenanthroline-2,9-dicarboxylic acid) and [Eu(pzpda)2 ]( ) (pzpda=pyrazino[2,3-f][1,10]phenanthroline-7,10-dicarboxylic acid) in aqueous solutions containing various amino acids. The selectivity of these complexes towards amino acids enabled them to be used as chiral sensors and their behavior was compared with that of [Eu(pda)2 ](-) (pda=1,10-phenanthroline-2,9 dicarboxylic acid). As these Eu(III) complexes have achiral D2d structures under ordinary conditions, there were no CPL signals in the emission assigned to f-f transitions. However, when the solutions contained particular amino acids they exhibited detectable CPL signals with glum values of about 0.1 (glum =CPL/2 TL; TL=total luminescence). On examining 13 amino acids with these three Eu(III) complexes, it was found that whether an amino acid induced a detectable CPL depended on the Eu(III) complex ligands. For example, when ornithine was used as a chiral agent, only [Eu(dppda)2 ](-) exhibited intense CPL in aqueous solutions of 10(-2) mol dm(-3) . Steep amino acid concentration dependence suggested that CPL in [Eu(dppda)2 ](-) and [Eu(pzpda)2 ](-) was induced by the association of four or more amino acid molecules, whereas CPL in [Eu(pda)2 ](-) was induced by association of two arginine molecules. PMID- 27380555 TI - Angelman Syndrome in the Portrait of a Child With a Drawing by Giovanni F. Caroto. PMID- 27380556 TI - Management of heparin-induced thrombocytopenia. AB - PURPOSE OF REVIEW: The purpose of this review is to summarize recent findings on heparin-induced thrombocytopenia (HIT), a prothrombotic disorder caused by platelet-activating IgG targeting platelet factor 4 (PF4)/polyanion complexes. RECENT FINDINGS: HIT can explain unusual clinical events, including adrenal hemorrhages, arterial/intracardiac thrombosis, skin necrosis, anaphylactoid reactions, and disseminated intravascular coagulation. Sometimes, HIT begins/worsens after stopping heparin ('delayed-onset' HIT). Various HIT mimicking disorders are recognized (e.g., acute disseminated intravascular coagulation/'shock liver' with limb ischemia). HIT has features of both B-cell and T-cell immune responses; uptake of PF4/heparin complexes into macrophages ('macropinocytosis') facilitates the anti-PF4/heparin immune response. Antibody induced activation of monocytes and platelets via their FcgammaIIA receptors triggers an intense procoagulant response. Sometimes, HIT antibodies recognize PF4 bound to (platelet-associated) chondroitin sulfate, explaining how HIT might occur without concurrent or recent heparin (delayed-onset HIT, 'spontaneous HIT syndrome'). The molecular structure of HIT antigen(s) has been characterized, providing a rationale for future drug design to avoid HIT and improve its treatment. The poor correlation between partial thromboplastin time and plasma argatroban levels (risking subtherapeutic anticoagulation) and need for intravenous administration of argatroban have led to increasing 'off-label' treatment with fondaparinux or one of the direct oral anticoagulants. SUMMARY: Understanding the molecular mechanisms and unusual clinical features of HIT will improve its management. PMID- 27380558 TI - Controversies in the treatment of immune thrombocytopenia. AB - PURPOSE OF REVIEW: We address three current controversies in management of immune thrombocytopenia (ITP): Should asymptomatic children with newly diagnosed ITP and severe thrombocytopenia be treated? Does intensification of up-front therapy in adults with newly diagnosed ITP impact long-term outcomes? Is splenectomy still the second-line treatment of choice in adults with chronic ITP? RECENT FINDINGS: Severe bleeding is rare in children with ITP. There is little evidence that the platelet count predicts or that treatment prevents severe bleeding in this population. Intensified treatment with high-dose dexamethasone and rituximab in adults with newly diagnosed ITP is associated with improved platelet responses at 6 and 12 months but greater toxicity compared with standard therapy. Rituximab and thrombopoietin receptor agonists have emerged as suitable alternatives to splenectomy for second-line management of adults with chronic ITP. SUMMARY: We generally observe children with newly diagnosed ITP and mild or no bleeding symptoms, irrespective of platelet count. We do not routinely use intensified up front therapy in adults with newly diagnosed ITP. We discuss the advantages and disadvantages of splenectomy, rituximab, and thrombopoietin receptor agonists with our patients and make a joint decision that takes into consideration age, comorbidities, lifestyle, values, preferences, and financial considerations. PMID- 27380557 TI - Antithrombotic potential of the contact activation pathway. AB - PURPOSE OF REVIEW: This report examines the mechanism(s) by which each protein of the contact activation system - factor XII (FXII), high-molecular-weight kininogen, and prekallikrein - influences thrombosis risk. RECENT FINDINGS: FXII generates thrombin through contact activation via interaction with artificial surfaces as on medical instruments such as indwelling catheters, mechanical valves, stents, and ventricular assist devices. Inhibition of FXIIa-mediated contact activation prevents thrombosis under contact activation circumstances without affecting hemostasis. Current studies suggest that high-molecular-weight kininogen deficiency parallels that of FXII and inhibits contact activation. Prekallikrein inhibition contributes to thrombosis prevention by contact activation inhibition in the nylon monofilament model of transient middle cerebral artery occlusion. However, in arterial thrombosis models where reactive oxygen species are generated, prekallikrein deficiency results in downregulation of vessel wall tissue factor generation with reduced thrombin generation. Exploiting this latter prekallikrein pathway for thrombosis risk reduction provides a general, overall reduced tissue factor, antithrombotic pathway without risk for bleeding. SUMMARY: These investigations indicate that the proteins of the contact activation and kallikrein/kinin systems influence thrombosis risk by several mechanisms and understanding of these pathway provides insight into several novel targets to prevent thrombosis without increase in bleeding risk. PMID- 27380559 TI - The role of the tissue factor pathway in haemostasis and beyond. AB - PURPOSE OF REVIEW: The role of tissue factor (TF) in the initiation of the blood coagulation network leading to generation of a fibrin clot has been well defined over the past 50 years. Although much is known about this sequence of events and its regulation, many important questions remain unresolved. More recently, a complex role for TF in cellular processes independent of fibrin generation has emerged. This review summarizes some of the advances in this field. RECENT FINDINGS: TF is the cellular receptor and cofactor for factor VII/VIIa; however, controversy still surrounds expression of TF within the vasculature, the role of circulating microvesicle pools of TF and mechanisms of 'encryption' of TF activity. However, there have been significant advances in the role of TF initiated cell signalling. Lastly, an alternatively spliced TF transcript has been identified and some insights into its role in cancer cell metastasis/proliferation have been elucidated. SUMMARY: Understanding of TF structure function has increased substantially; however, multiple controversies still surround some aspects of its regulation. TF has emerged as a pivotal player in orchestrating not only fibrin generation but wound repair. Derangement of these repair processes contributes significantly to the pathophysiology of a number of disease processes. PMID- 27380560 TI - White Matter Changes and Cognitive Decline in a Ten-Year Follow-Up Period: A Pilot Study on a Single-Center Cohort from the Leukoaraiosis and Disability Study. AB - AIMS: To describe the contribution of white matter lesions to the long-term neuropsychological profiles of different groups of clinical diagnoses, and to identify neuropsychological predictors of cognitive impairment in a 10-year follow-up. METHODS: The Lisbon subcohort of the Leukoaraiosis and Disability (LADIS) study was re-evaluated performing a clinical, functional and cognitive evaluation [including Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) and ADAS-Cog with the extension for vascular impairment (VADAS-Cog), the 9-word version of the California Verbal Learning Test (CVLT-9), the Trail-Making test and the Stroop test] as well as an MRI scan. Using clinical diagnostic criteria, participants were identified as having no cognitive impairment (NI), cognitive impairment but no dementia (CIND) or dementia (DEM), and the effect of time on clinical diagnosis and neuropsychological profiles was analyzed. RESULTS: From the initial group of 66 participants, 37 out of 41 survivors (90%) were re-evaluated (mean age 81.40 years, 57% women). Fifteen patients (41%) had DEM, 12 (32%) CIND and 10 (27%) NI. Over time, the three groups presented distinct profiles in the MMSE [F2, 62 = 15.85, p = 0.000], ADAS [F2, 62 = 15.85, p = 0.000] and VADAS [F2, 48 = 5.87, p = 0.008]. Logistic regression analysis identified higher scores on MMSE (beta = 1.14, p = 0.03, OR = 3.13, 95% CI 1.09-8.97) as predictors of NI after 10 years of follow-up. CONCLUSION: Higher scores on baseline MMSE were the only neuropsychological predictors of NI after 10 years. PMID- 27380561 TI - Clinical, Histological, and Histomorphometric Evaluation of Demineralized Freeze Dried Cortical Block Allografts for Alveolar Ridge Augmentation. AB - Autogenous bone-block grafts are the "gold standard" for block bone grafting, but have several disadvantages. Allografts have the potential to overcome these disadvantages. The purpose of this study was to evaluate the clinical and histomorphometric features of demineralized freeze-dried cortical block allografts (DCBA) used for ridge augmentation. Eleven patients who showed bone deficiencies of <5 mm in the horizontal plane were included in this study. The recipient sites were reconstructed with DCBA. The primary outcomes of interest were bone-width measurements, postoperative clinical evaluations, and histomorphometric analysis of the biopsy samples collected during the implant surgery. Clinical analysis showed that the mean gain in horizontal bone was 1.65 +/- 0.14 mm, and that the mean percentage of graft resorption was 5.39 +/- 2.18%. On postoperative day 7, edema, pain, and bruising were observed in 18.2%, 0%, and 9.1% of the patients, respectively. In the biopsy samples, the mean percentages of newly formed bone, residual block allograft, and marrow and connective tissue were 40.30 +/- 24.59%, 40.39 +/- 21.36%, and 19.30 +/- 15.07%, respectively. All of the block grafts were successfully integrated into the recipient sites. DCBA may be a viable alternative for treating both deficient maxillary and mandibular alveolar ridges. PMID- 27380562 TI - Congenital Midline Sinus of the Upper Lip. AB - An extremely rare patient of congenital midline sinus of the upper lip in a 2 year-old boy is presented. The sinus was located on the midline of the philtrum just below the base of the columella. Surgical removal of the sinus was performed via an extra- and inraoral approach. Histopathological examination of the resected sinus revealed it to be lined by keratinized stratified squamous epithelium with sebaceous glands and hair follicles. Three postulates can account for the formation of the congenital midline sinus of the upper lip: the fusion theory, the merging theory, and the invagination theory. However, the etiology of this rare abnormality remains obscure. PMID- 27380563 TI - Frontalis Sling Surgery With IBCN-Ritleng Probe: A New Technique With a 20-Gauge Catheter. AB - INTRODUCTION: Frontalis sling surgery is the reference procedure for severe ptosis due to poor Levator function. Autologous or synthetic materials are used for lifting the upper eyelid. OBJECTIVE: To describe a new technique of passage of a silicon wire through a 20-gauge intravenous catheter and to explore literature. METHODS: A 83-year-old male patient with simple, severe ptosis with previous levator resection surgery (7 month before) had frontalis sling with a silicone IBCN wire placed under local anesthesia with a closed technique. It consisted in realization of 3 punctiform incisions upper the eyebrow, through which a 20G intravenous catheter was inserted and droven to the free border of the upper eyelid. The polypropylene part of the IBCN probe silicone tube, IBCN set, was interlocked into the needle tip, enabling to drag the wire through its tunnel without eyelid dissection. The body of the IBCN probe was consequently placed on the free edge of the eyelid, whereas its 2 ends were tied under the middle upper eyebrow incision, enabling to adjust tension of the probe according to the severity of ptosis. The node was kept subcutaneously, allowing correction "on demand" of wire tension in the future by the surgeon. RESULTS: No infections, exposures, or granuloma formations were seen in our patient at 2 months, whereas visual field was improved and the patient fully satisfied. DISCUSSION: Small punctiform incisions and limited skin dissection offer a significant advantage, as well as the materials that are easy to access and cheap, in the frontalis sling surgery. CONCLUSION: The authors added to frontalis sling surgery a simple and cost-effective alternative technique of passage of a subcutaneous probe, with an IBCN wire whose dimensions fit perfectly a 20-gauge intravenous catheter and allowing later correction "on demand" of the ptosis. PMID- 27380564 TI - Secondary Cleft Nasal Deformity Correction Using Bioabsorbable Mesh. AB - INTRODUCTION: Septorhinoplasty in cleft patients is relatively difficult to perform and the outcomes are often unsatisfactory owing to weakness of the cartilage. Therefore, providing support to the cartilage is necessary. The authors used bioabsorbable mesh as a spreader or batten graft to support the septum in cleft patients those with weak cartilages. The purpose of this study was to evaluate the efficacy of bioabsorbable mesh when performing septorhinoplasty in cleft patients. METHODS: Between 2009 and 2013, 34 patients with cleft lip and nose underwent open septorhinoplasty by using bioabsorbable mesh at the Konkuk University Medical Center. The authors determined the nasolabial angle, Goode ratio, alar base-nasal tip-columellar base angle, and columellar axis angle and performed a panel evaluation. RESULTS: In all, 29 of the 34 patients were included; 5 patients were excluded as lost to follow-up. The nasolabial angle increased from 85.69 degrees to 91.62 degrees (P = 0.0032), and the mean Goode ratio increased from 0.51 to 0.55, which was approximately the ideal value (P = 0.0017). The alar base-nasal tip-columellar base angle decreased from 36.28 to 31.74 (P < 0.0001). The columellar axis angle increased from 82.36 to 86.90 (P < 0.0001). DISCUSSION: As bioabsorbable mesh can provide strong support, results in good esthetic outcomes, and causes minimal complications, it can be used in septorhinoplasty for cleft patients. PMID- 27380565 TI - A Cephalometric Analysis on Magnitudes and Shape of Sella Turcica. AB - Familiarity with the shape and dimensions of sella turcica is important to recognize and manage pathological conditions of pituitary gland as well as for orthodontic treatment planning. The present study aims to describe the morphology and dimensions of sella turcica from Indian population, using lateral cephalograms to set a reference data for comparison among different races. The study used 36 lateral skull radiographs of both sexes between age group of 13 to 18 years. Shape of sella turcica was noted by visual inspection. Length, height anterior, height median, height posterior, distance between frontonasal suture and mental spine to midpoint of posterior clinoid process, and tuberculum sella were measured using digital vernier caliper with reference to Frankfort line. The results of the study revealed that mean length, height anterior, height median, height posterior were larger in females than in males. The morphological types identified include pointed posterior clinoid process with rounded hypophyseal fossa, hooked posterior clinoid process with rounded hypophyseal fossa, hooked posterior clinoid process with flask-shaped hypophyseal fossa. These observations would be beneficial for the clinicians and orthodontists to design treatment planning in pathology of pituitary gland and in correcting dentofacial anomalies. PMID- 27380566 TI - Ocular Motility After Repair of Combined Medial and Inferior Orbital Wall Fractures With Extended Conjunctival Incision With Inferior Oblique Reattachment. AB - PURPOSE: To describe ocular motility and effectiveness of an extended conjunctival incision with reattachment of the inferior oblique muscle to repair combined orbital medial and inferior wall fractures. METHODS: The authors retrospectively studied 20 eyes from 20 patients who underwent combined orbital medial and inferior wall fractures surgery with reattachment of the inferior oblique muscle from January 2007 to December 2011. Single large L-shaped implant was inserted into the fracture site. All patients were evaluated preoperatively and postoperatively at 1, 3, and 6 months, by computed tomography, Hertel exophthalmometry, the Hess test of ocular motility, and the Goldmann diplopia test. RESULTS: Sixteen patients (80%) had no significant enophthalmos or diplopia after surgery. Inferior oblique motility was not changed in 12 patients (60%) after reattachment of the inferior oblique muscle. After 1 month, inferior oblique underaction was presented in 8 patients (40%) and in 4 patients (20%) after 6 months. Finally, only 2 patients (10%) had the inferior oblique underaction remained, it was not improved. CONCLUSIONS: The extended conjunctival incision with reattachment of the inferior oblique muscle for combined orbital wall fracture repair offers a wide surgical field and space for a single large implant insertion and corrects the enopthalmos. The reattachment of the inferior oblique muscle does not contribute to the development of inferior oblique underactions or diplopia that was resolved spontaneously within 6 months after surgery. PMID- 27380567 TI - Bleeding Rate After Tooth Extraction in Patients Under Oral Anticoagulant Therapy. AB - OBJECTIVES: The aim of this single-cohort prospective study was to evaluate the risk of adverse outcomes after tooth extraction in patients suffering from cardiovascular disorders and under oral anticoagulant therapy with an international normalized ratio within the value of 3.0. METHODS: Two hundred ninety-three patients (mean age of 58.7 years) were enrolled and 560 tooth extractions were performed. Fresh extraction sockets were treated with collagen tablets and sutures. The risk of increased bleeding rate was evaluated for type of drug therapy (acenocoumarol or warfarin), type of cardiovascular diseases, and number of tooth extractions. Level of significance was set at 0.05. RESULTS: The overall bleeding event rate was 6.8%. Among patients who had bleeding events, 4 suffered from valvular disorders, whereas 11 suffered from arrhythmias (8) or cardiomyopathies (3). The remaining 5 patients had a history of cardiomyopathy and arrhythmia.The bleeding events in patients who had more than 2 tooth extractions were significantly higher than those observed in patients who had only 1 tooth extraction (P <0.05). CONCLUSION: Patients who received more than 2 tooth extractions, who were under treatment with acenocoumarol, and who suffered from multiple cardiovascular diseases were at high risk for bleeding events. PMID- 27380568 TI - Apert Syndrome: Outcomes From the Australian Craniofacial Unit's Birth to Maturity Management Protocol. AB - The complex, progressive, multisystem nature of Apert syndrome presents many challenges to managing surgeons. Based on the pioneering work of Paul Tessier, the senior author developed a multidisciplinary birth to maturity management protocol for Apert syndrome. Between 1975 and 2014 the Australian Craniofacial Unit has treated 174 Apert syndrome patients and 28 have completed full protocol management. This paper reviews the scientific contribution made to the management of Apert syndrome by the Australian Craniofacial Unit, the development and evolution of the protocol and presents comprehensive data on the surgical and nonsurgical craniofacial interventions, and outcomes for the 28 patients who have completed the programme; 26 had normal visual acuity, 22 had normal hearing, 20 achieved normal or nearly normal speech, 24 a functional class I occlusion, 18 completed mainstream schooling of whom at least 8 went on to tertiary education, at least 13 gained employment and 15 developed good social groups. These outcomes equal or exceed those presented by other authors and provide compelling evidence of the value of protocol management in clinical outcomes, in addition to their value in international collaboration, and scientific development of future therapeutic strategies for the management of Apert syndrome. PMID- 27380569 TI - Management of Craniosynostosis at an Advanced Age: Controversies, Clinical Findings, and Surgical Treatment. AB - BACKGROUND: The natural history of unrepaired craniosynostosis is not well defined. Delayed surgical intervention carries greater risk of postoperative complications and its functional benefits for older patients are poorly characterized. The authors reviewed patients in whom children presented beyond 1 year of age to better understand the natural history of craniosynostosis, and the risk-benefit relationship for delayed reconstruction. METHODS: After institutional IRB approval the authors conducted a retrospective review of patients who presented after 1 year of age with craniosynostosis. Type of craniosynostosis, age at evaluation, medical history, surgical findings, developmental abnormalities, ophthalmologic findings, and clinical course were reviewed. RESULTS: Ten patients with delayed presentation for craniosynostosis were identified. The mean age at presentation was 6.8 years +/- 4.2 years (range, 3-17 years). Seven of 10 patients presented with developmental delay. Five patients presented with debilitating headaches. Five patients presented with comorbid Chiari malformations, 3 of whom required surgical decompression. Two patients had papilledema. Four patients underwent intracranial pressure monitoring, with elevated pressures found in 3 patients. Six patients underwent delayed cranial vault remodeling. There were no peri- or postoperative complications, including infection or residual bony defects, in those undergoing delayed operation. CONCLUSIONS: Children who present in a delayed fashion with unrepaired craniosynostosis have high rates of debilitating headaches, developmental delays, head shape anomalies, and Chiari malformation. Five patients reporting preoperative headaches noted subjective improvements in headaches following delayed operation. Cranial reconstruction can be safely performed at an older age and is appropriate to consider in carefully selected patients for aesthetic and/or functional concerns. PMID- 27380570 TI - Inferior Alveolar Nerve Mobilization Using Ultrasonic Surgery With Crestal Approach Technique, Followed by Immediate Implant Insertion: Evaluation of Neurosensory Disturbance. AB - Many techniques are described for atrophied mandibles rehabilitation. This article reports on 12 clinical patients of severely atrophied posterior mandibles. In all the patients, a cone beam is performed before the crestal surgical approach to inferior alveolar nerve (IAN) mobilization. For the realization of this technique the piezosurgery device was used to minimize IAN injuries. With the help of this device the selective cutting of the bone has been possible until IAN exposure, in the implant placement site. At the same time, the authors performed the implant osteotomy and implant placement. After 4 months of healing, all implants were osseointegrated and the implant-supported bridges were done.Evaluation by means of neurosurgery function test over a 36-months period found that all patients had a return to normal sensation, after a brief period of neurosensory disturbance. PMID- 27380571 TI - Endoscope-Assisted Transoral Fixation of Mandibular Condyle Fractures: Submandibular Versus Transoral Endoscopic Approach. AB - In recent years, endoscope-assisted transoral approach for condylar fracture treatment has attracted much attention. However, the surgical approach is technically challenging: the procedure requires specialized instruments and the surgeons experience a steep learning curve. During the transoral endoscopic (TE) approach several instruments are positioned through a narrow oral incision making endoscope maneuvering very difficult. For this reason, the authors changed the entry port of the endoscope from transoral to submandibular area through a small stab incision. The aim of this study is to assess the advantage of using the submandibular endoscopic intraoral approach (SEI).The SEI approach requires intraoral incision for fracture reduction and fixation, and 4 mm size submandibular stab incision for endoscope and traction wires. Fifteen patients with condyle neck and subcondyle fractures were operated under the submandibular approach and 15 patients with the same diagnosis were operated under the standard TE approach.The SEI approach allowed clear visualization of the posterior margin of the ramus and condyle, and the visual axis was parallel to the condyle ramus unit. The TE approach clearly shows the anterior margin of the condyle and the sigmoid notch. The surgical time of the SEI group was 128 minutes and the TE group was 120 minutes (P >0.05). All patients in the TE endoscope group were fixated with the trocar system, but only 2 lower neck fracture patients in the SEI group required a trocar. The other 13 subcondyle fractures were fixated with an angulated screw driver (P <0.05). There were no differences in complication and surgical outcomes.The submandibular endoscopic approach has an advantage of having more space with good visualization, and facilitated the use of an angulated screw driver. PMID- 27380572 TI - Microvascular Decompression for Idiopathic Primary Trigeminal Neuralgia in Patients Over 75 Years of Age. AB - OBJECTIVE: In the present study, the authors appraised the results of microvascular decompression in patients over 75 years of age. METHODS: From June 2009 to June 2013, a number of 108 aged patients with primary trigeminal neuralgia experienced microvascular decompression. The authors present a retrospective review of medical records and compared the results with those of a control group of 302 younger patients. RESULTS: The mean follow-up period was 3 years. No statistically marked differences were observed between the 2 groups in terms of rate of pain control, recurrences, complications. The duration of operation in the elderly group was markedly shorter than that in the younger group. CONCLUSION: Microvascular decompression is a liable and safe surgical method for aged patients with primary trigeminal neuralgia. Unless the aged patients cannot bear general anesthesia, they should have the chance to select microvascular decompression. PMID- 27380573 TI - Tomographic Evaluation of Accessory Canals Penetrating at the Inner Side of the Anterior Region of Mandibles. AB - BACKGROUND: The anterior region of the mandible is generally considered to be a safe region to invasive procedures; however, on its internal face, uncountable penetrating canals may be encountered. OBJECTIVE: To perform morphometrical and topographical analysis of endosseous canals located at the inner side of the mandibular anterior region, using cone-beam computed tomography. METHODS: Forty six examinations were digitally analyzed. Localization of canals in relation to the midline, trajectories, communications between other anatomic structures and relation with teeth were evaluated. Longitudinal and transversal diameters of the canals and distances to the lower edge and symphysis of the mandible were also measured. RESULTS: All individuals had at least 1 canal, with a mean of 2.3 and higher prevalence in the midline region. The adjacent teeth to the canals were usually the incisors but the authors could not determine the connected anatomical structure in most patients. Both the mean diameters were quite similar, about 1 mm; however, the trajectories and distances to the lower edge and symphysis of mandible showed a remarkable heterogeneity among the individuals. CONCLUSIONS: These endosseous canals are consistent and clinically relevant findings and should never be underestimated by professionals. PMID- 27380574 TI - The Mini-Zygoma Reduction Surgery: A Simple and Reliable Approach for Mid-Face Narrowing. AB - Reduction of mid-face width is a major concern in Asian facial contouring surgery, and some patients want their mild or borderline problems to be improved in a minimally invasive manner. The authors' mini-zygoma reduction surgery technique is indicated for patients who seek both minimal invasiveness and reliability. Patients presenting with a wide mid-face and isolated zygomatic arch protrusion without severe zygomatic body prominence were included into the study. All surgeries are performed under local anesthesia and on an outpatient basis. Through temporal and sideburn incisions, complete osteotomy was performed on the temporal process of the zygomatic body and just in front of the anterior tubercle of the zygomatic arch. After transposition to a proper inward position, the osteotomized segment was rigidly fixed on the zygomatic arch with metal fixtures. All surgeries were successfully performed without excessive blood loss or any unpredicted events. Over the 6 to 18-month follow-up period, most patients were satisfied with the aesthetic results of the surgery, the rapid recovery, and the minimal postoperative swelling. Even with a 1-point fixation, the segment remained stable and did not show displacement of the bony segment. In patients showing a minimal zygomatic arch prominence and seeking minimally invasive surgery, the proposed technique can be a proper surgical option with reliable and predictable results. The surgery can be performed without general anesthesia and on an outpatient basis, thereby resulting in prompt postoperative recovery. Predictability and reliability is assured with rigid fixation with a metal fixture on the zygomatic arch. PMID- 27380575 TI - An Innovative Decompression Device to Treat Odontogenic Cysts. AB - The author presents an innovative device to decompress odontogenic cystic lesions of the jawbones. Its use and characteristics are described. PMID- 27380576 TI - Single-Stage Surgical Reconstruction of Posttraumatic Compound Complex Fronto Basal Cranial Vault Fracture in a Resource-Limited Practice. AB - BACKGROUND: The extant literature on the surgical treatment of posttraumatic compound, complex frontal basal calvarial skull fracture suggests that this be a staged procedure. There are many socioeconomic constraints in low-resource regions of the world to the feasibility of this standard practice. METHODS: A single-stage operative procedure for the surgical treatment of these fractures in a neurosurgery practice in Nigeria is here annotated. In addition, an observational outcome analysis of this surgical technique in a prospective consecutive cohort of patients over a 6-year period is presented. RESULTS: Fourteen patients, all males, mean age 33.9 years (SD, 6.6) underwent this surgical procedure. Majority were late neurosurgical referrals, hence median time to surgery was 96 hours (range, 48-2160). Twelve patients (85.7%) had history of loss of consciousness, median duration of 34 hours; 7 (50%) had associated brain contusions; 6 (43%) significant pneumocephalus; and acute extradural and subdural haematoma in 4 and 2 patients respectively. The surgery was successful in all; 13 (93%) had normal outcome on the Glasgow outcome scale at hospital discharge; 12 have been followed up for 1 to 72 months, median 33. Seven of these were for 30 months or more. There was no patient of surgical site infection in the perioperative or the follow-up period to date. The aesthetic outcome was also acceptable. CONCLUSION: The pragmatic surgical technique herein annotated appears clinically and aesthetically effectual in the operative treatment of compound, complex frontal basal cranial vault fracture. PMID- 27380577 TI - A Perioperative Risk Comparison of Posterior Vault Distraction Osteogenesis in an Older Pediatric Population. AB - There is a growing literature on the advantages of posterior cranial vault distraction osteogenesis (PVDO) in infants, particularly those with syndromic and multisuture craniosynostosis. This study aims to compare perioperative outcomes of PVDO in older patients to those of infants. A prospective craniofacial database was queried for patients aged 5 and older undergoing PVDO; controls were diagnosis-matched infants. Demographic, perioperative, and distraction data was compared using a 2-sample t test and Fisher exact test.Twenty patients met inclusion criteria, and all had syndromic craniosynostosis. Mean age was 9.2 years for the older group, and 0.7 years for the younger. Older children had less weight-based blood loss (mean 58.6 +/- 38.8 versus 14.6 +/- 7.0 cc/kg, control versus older, P = 0.0092) and weight-based transfusion (mean 70.1 +/- 37.2 versus 21.2 +/- 9.9 cc/kg, control versus older, P = 0.0023); other perioperative variables were similar including duration of surgery, length of stay, distance distracted, time in consolidation, and length of follow-up. All patients in both groups successfully completed PVDO, and all older patients had resolution of papilledema and/or headaches. One from each group developed a wound infection that was treated with oral antibiotics.Posterior cranial vault distraction osteogenesis is a safe and efficacious for cranial vault expansion in syndromic craniosynostosis, with similar perioperative outcomes in older children as compared to infants. Posterior cranial vault distraction osteogenesis may be a reasonable alternative in older syndromic patients with acceptable frontal morphology and concerns for increased intracranial pressure. PMID- 27380578 TI - Alloderm Covering Over Titanium Cranioplasty May Minimize Contour Deformities in the Frontal Bone Position. AB - BACKGROUND: Titanium cranioplasty is commonly used for surgical closure of skull defects post craniectomy. Superficial implantation of the mesh can result in discomfort, palpability, and in extreme patients, exposure of the mesh. Exposed titanium mesh can be complicated by infections and often requires implant revision or removal. Generally, the contour of the titanium mesh is camouflaged in the hairline of the patient and any aesthetic complication can remain inconspicuous. However, in the frontal bone position the thin hairless forehead skin often may not easily hide the contour of the underlying titanium mesh. OBJECTIVES: The goal of this study was to demonstrate the usage of an alloderm covering over the titanium cranioplasty to possibly minimize the contour irregularities of titanium. SURGICAL TECHNIQUE: Our index patient, a 22-year-old woman, was operated for left frontal craniectomy for frontal bone tumor extending to brain parenchyma. This resulted in a surgical defect that was repaired with titanium mesh cranioplasty and dural patch. It was felt that the patient would potentially feel and see the titanium mesh cranioplasty under the thin frontalis muscle. Therefore, over top of the titanium mesh a remnant piece of AlloDerm unused after the dural patch was placed to buffer the potential contour deformity. Postoperatively, the contour appears natural and the patient does not report any complaints of discomfort or mesh palpability. CONCLUSION: In a thin skinned patient undergoing titanium mesh cranioplasty, the risk of mesh palpability or exposure can be significant, especially in areas of non-hair bearing scalp and the protruding areas of the skull. Alloderm covering over the titanium mesh can provide improved aesthetic outcomes by minimizing contour deformity and may serve as an additional buffer in thin scalp. PMID- 27380579 TI - The Effect of Septoplasty on Voice Performance in Patients With Severe and Mild Nasal Septal Deviation. AB - OBJECTIVE: The authors aimed to analyze the effect of septoplasty, performed in 2 groups with different grades of nasal septal deviation (NSD), on voice performance. METHODS: A total of 43 patients who had septoplasty due to NSD and were included in the study. The study groups were divided into 2 groups as groups A and B. The patients in group A had severe NSD, and 1 of the nasal cavity was obstructed totally or near totally. In group B, the NSD narrowed the nasal passage, and the deviation was not severe. The voice performance was analyzed preoperatively, and 1 month after surgery with both objective and subjective methods. Objective analysis included acoustic voice analysis, and measurement of F0, jitter %, shimmer %. Preoperative and postoperative F0, jitter %, shimmer %, and Voice Handicap Index-30 (VHI-30) were compared in groups A and B. RESULTS: F0 showed a statistically significant improvement after surgery in group A (P <0.001). Jitter %, shimmer %, and VHI-30 scores also improved after surgery, without any statistical significance. In group B, preoperative and postoperative F0, jitter %, and shimmer % were similar. However, VHI-30 scores showed a significant improvement postoperatively (P = 0.005). Comparison of groups A and B for improvements of the voice parameters revealed that group A showed improvements in all voice parameters, and the improvements of F0 and shimmer % were statistically significant. CONCLUSION: Septoplasty performed for severe NSD obstructing nasal lumen totally or near totally results in significant improvements in the voice performance. PMID- 27380580 TI - Emergency Management of High-Energy Shell Fragment Midface Complex Injuries. AB - Distinctive mechanisms of heavy artillery and improvised explosive device detonation result in a blast and "spray" of high-energy fragments of diverse shapes, sizes, and characteristics. Associated midface complex injuries differ in both severity and complexity of the anatomical structures involved. Management challenges begin with lifesaving, which is complicated by airway compromise, severe hemorrhage, and unique injuries of the maxillae, nose, and naso orbitoethmoid.The patients presented fragment impact on the face lateral side directed to other side leads to tissues blown away at the point of high-energy exits, while no survival seen of enface shrapnel hit directed antroposterior toward "cervical spine, intracranial, internal and external carotid arteries and internal jugular vein."Twenty-two patients were selected from unquantified patients who had sustained massive midface shell fragment injuries. To preserve midface architecture, healing, and function, iodoform paste on ribbon gauze packs were utilized successfully. An iodoform paste on ribbon gauze pack serves the dual purpose of preserving the shape and scaffolding of the crushed maxillary sinus wall and buttresses fragments in position for healing. It also acts as a wet pack dressing for denuded bone fragments, stopping bleeding and having antimicrobial properties for severely lacerated wounds. For total or partial nasal tissue loss, a successful procedure consists of definitive early scaffolding stabilization using an intranasal, modified portex tracheostomy tube stent to preserve the internal shape of the nasal pyramid. PMID- 27380581 TI - Surgical Treatment of Complex Orbital Fracture. PMID- 27380582 TI - The Anti-Inflammatory and Antioxidant Effects of Curcumin in Middle Ear Infection. AB - AIM: To investigate and analyze the anti-inflammatory and antioxidant efficacy of curcumin in experimentally induced middle ear infection. METHOD: Twenty-four Wistar albino rats with otomicroscopic examination findings within normal limits were included in the study. Study groups were established after Streptococcus pneumoniae was inoculated into the middle ear cavity of all rats. No medication was administered to Group 1, the control group. Group 2 was administered 50 mg/kg/day amoxicillin intraperitoneally. Group 3 was administered 50 mg/kg/day amoxicillin together with 30 mg/kg/day curcumin intraperitoneally. Blood specimens and temporal bones were collected on the 10th day of medication from the 22 rats in which acute otitis media developed. Serum glutathione peroxidase and superoxide dismutase activities and malondialdehyde levels were measured. Inflammatory cell infiltration, vascular proliferation, and epithelial proliferation were assessed histopathologically in middle ear mucosa specimens, and the results were compared among the groups. RESULTS: Malondialdehyde levels in the group given curcumin were significantly lower than those of the control group, while serum glutathione peroxidase activity was also lower compared to that of the control group. No significant difference was observed among the groups in terms of superoxide dismutase activity. Although there were no significant findings in terms of histopathological data, epithelial proliferation in the groups receiving antibiotherapy was suppressed compared to the control group. Similarly, curcumin was observed to have a positive effect on inflammatory cell infiltration. No significant changes were observed in terms of vascular proliferation. CONCLUSION: With its wide and safe dose range, curcumin represents grounds for optimism in terms of anti-inflammatory treatment in acute otitis media. PMID- 27380583 TI - Reconstruction of Eyelids and Related Structures. AB - Eyelids and related structures such as ligamentous and lacrimal system make the reconstruction of the periorbital area a challenge. The authors present 5 patients with periorbital reconstruction after tumor excision or trauma with special considerations. A detailed analysis of the problem and reconstruction of all of the injured systems or structures are mandatory to achieve a satisfactory result on the periorbital area. PMID- 27380584 TI - Surgical Approach, Findings, and Eight-Year Follow-Up in a Twenty-Nine Year Old Female With Freeman-Sheldon Syndrome Presenting With Blepharophimosis Causing Near-Complete Visual Obstruction. AB - The authors describe the surgical approach, findings, and 8-year follow-up in a 29-year-old woman, with severe Freeman-Sheldon syndrome, presenting with congenital blepharophimosis of both upper eyelids resulting in near-complete functional visual obstruction. To avoid possible Freeman-Sheldon syndrome associated complications of malignant hyperthermia, difficult vascular access, and challenging endotracheal intubation, the surgery was completed under local anesthesia without sedation, and anatomical and functional correction was immediate and remained stable at 8-year follow-up. Unlike many congenital craniofacial syndromes, which frequently involve life-long impairments, important implications exist for plastic surgeons to facilitate opportunities for patients to overcome functional limitations. PMID- 27380585 TI - Mesiotemporal Disconnection and Hypoactivity in Kluver-Bucy Syndrome: Case Series and Literature Review. AB - OBJECTIVE: Kluver-Bucy syndrome (KBS) is often perceived as rare and limited to cases with bilateral amygdala destruction. In fact, various alternate mechanisms may be involved, warranting exploration of the syndrome's presentation, pathophysiology, prognosis, and management. DATA SOURCES: Clinical management and the electronic medical records were examined for 2 patients diagnosed with partial KBS (ICD-10 F07.0) after experiencing >= 3 of the following: placidity, indiscriminate dietary behavior, hyperorality, hypersexuality, visual agnosia, and hypermetamorphosis. A literature search was performed in April 2015 by using the keyword Kluver-Bucy in PubMed and Ovid databases for English language publications since inception. Additionally, the authors reviewed the reference list of these publications in order to identify additional reports. STUDY SELECTION: Studies were included if they had information about presentation, pathophysiology, syndrome treatment or management, and course of KBS. DATA EXTRACTION: Information about our KBS cases was obtained by reviewing electronic medical records and by direct observation of the patients. A total of 186 (PubMed) and 137 (Ovid) publications were identified in each database. We ultimately reviewed 109 articles containing information about KBS, finding 51 publications addressing relevant aspects of this syndrome. RESULTS: The first case demonstrates KBS secondary to mesiotemporal structural atrophy, and the second illustrates transient KBS due to functional, postictal, hypoactivity within such structures. Literature review and discussion regarding both prognosis and treatment of KBS follows. CONCLUSIONS: Kluver-Bucy syndrome may be underreported due to a limited understanding of the syndrome as one necessitating bilateral amygdaloid destruction. The syndrome can be seen with damage/hypofunction of the hippocampal-amygdaloid complex and its projections. The prognosis of KBS is variable, and its treatment is based on a combination of environmental and pharmacologic measures. PMID- 27380586 TI - Understanding Interactions between Cellular Matrices and Metal Complexes: Methods To Improve Silver Nanodot-Specific Staining. AB - Metal complexes are frequently used for biological applications due to their special photophysical and chemical characteristics. Due to strong interactions between metals and biomacromolecules, a random staining of cytoplasm or nucleoplasm by the complexes results in a low signal-to-background ratio. In this study, we used luminescent silver nanodots as a model to investigate the major driving force for non-specific staining in cellular matrices. Even though some silver nanodot emitters exhibited excellent specific staining of nucleoli, labeling with nanodots was problematic owing to severe non-specific staining. Binding between silver and sulfhydryl group of proteins appeared to be the major factor that enforced the silver staining. The oxidation of thiol groups in cells with hexacyanoferrate(III) dramatically weakened the silver-cell interaction and consequently significantly improved the efficiency of targeted staining. PMID- 27380587 TI - Moderate Exercise for Nonalcoholic Fatty Liver Disease. PMID- 27380589 TI - Haemostatic patterns and bleeding scores of a genetically characterised Italian family with combined haemophilia A and type 1 von Willebrand disease. AB - : We report on the coinheritance of mild haemophilia A and type 1 von Willebrand disease (VWD) in a genetically characterized Italian family. The proband is a 56 year-old man carrying both the c.2167G>A mutation in the factor VIII (FVIII) gene (responsible for p.A723T substitution) and the c.4751A>G mutation (p.Y1584C) in the von Willebrand factor (VWF) gene. His FVIII and VWF levels were 9.8 and 43.2 IU/dl, respectively. His bleeding symptoms included mucocutaneous bleeding, haemarthrosis, and muscle haematomas. Using the bleeding assessment tool, a questionnaire currently employed in diagnosing VWD, the patient had a bleeding score of 27 as compared with the 10.2 +/- 3.4 found in patients with mild-to moderate haemophilia A, and 0-3 in normal men. One of the proband's two daughters (both obligate carriers of haemophilia A) also harboured the VWF p.Y1584C mutation. Her FVIII and VWF levels were 45.9 and 54 IU/dl, respectively, and her bleeding score was slightly higher than normal for women (6 vs. 0-5). The other daughter had a normal bleeding score, and so did the proband's father (with type 1 VWD) and mother (haemophilia A carrier). Discrepancies between haemostatic patterns and bleeding symptoms in cases of haemophilia A, as seen in our patient, suggest the need to search for other coagulation defects, especially involving VWF, which is the carrier of FVIII. Although the presence of a VWF mutation significantly exacerbates the haemorrhagic complications in patients with mild haemophilia A, it has only mild effects on haemophilia A carriers. PMID- 27380588 TI - CYP2C19 but not CYP2B6, CYP3A4, CYP3A5, ABCB1, PON1 or P2Y12 genetic polymorphism impacts antiplatelet response after clopidogrel in Koreans. AB - Clopidogrel response variability (CRV) is well documented, and may affect clinical outcomes. Impact of genetic polymorphisms is important for assessing and predicting CRV. The extensive evidence indicates the importance of CYP2C19 variants in reducing efficacy of clopidogrel. This study defined the impact of numerous genetic polymorphisms on CRV before and after percutaneous coronary interventions (PCI) exclusively in a Korean cohort assuming less genetic variability noise. One hundred and thirty-six patients of Korean origin undergoing PCI were included. Platelet reactivity was measured by VerifyNow assay before and after PCI. Genetic polymorphism of seven single nucleotides of CYP2B6, CYP2C19, CYP3A4, CYP3A5, ABCB1, PON1, and P2Y12 were evaluated and matched with platelet reactivity. Carriers of at least one CYP2C19*2 or *3 allele uniformly exhibited higher platelet reactivity compared to 0-carrier pre-PCI (odds ratio 3.1, 95% confidence interval 1.4-6.9, P < 0.01) and post-PCI (odds ratio 3.4, 95% confidence interval 1.7-6.8, P < 0.001). The carriers of other gene allele variants lack uniformed impact on CRV. The Korean carriers of CYP2C19*2 or *3 allele are linked to CRV, whereas CYP2B6, CYP3A4, CYP3A5, ABCB1, PON1, and P2Y12 failed to predict CRV. The exact clinical utility of these findings is uncertain, and requires a large randomized national trial for proof of concept. PMID- 27380590 TI - Probiotics in Childhood Diseases: From Basic Science to Guidelines in 20 Years of Research and Development. PMID- 27380591 TI - Gut Microbiota as a Target for Food Allergy. AB - PURPOSE OF REVIEW: The purpose of this review is to present an overview on the potential role of gut microbiota as target of intervention against food allergy. RECENT FINDINGS: Many studies suggest a key pathogenetic role for gut microbiota modifications (dysbiosis) in food allergy development. Several factors responsible for dysbiosis have been associated with the occurrence of food allergy, such as caesarean delivery, lack of breast milk, drugs use (mainly antibiotics and gastric acidity inhibitors), antiseptic agents use, and low fibers/hight fat diet. No specific bacterial taxa have been consistently associated with food allergy, but evidence suggests that gut dysbiosis occurs even before food allergy signs and symptoms presentation. Data from animal and human studies highlight the ability of particular bacterial taxa to ferment dietary fibers for the production of short chain fatty acids that affect host immunity and help to explain their health-promoting role. SUMMARY: Modulation of gut microbiota composition and/or function represents a promising strategy for treatment and prevention of food allergy in childhood. PMID- 27380592 TI - Probiotics, Prebiotics & Food allergy Prevention: Clinical Data in Children. AB - PURPOSE OF REVIEW: there are accruing evidences on the role of the intestinal microbiota in the development of allergic diseases among infants. Elaborating on this theoretical basis, studies did assess the possibilities to prevent allergic diseases in infancy through manipulation of the intestinal microbiota. We review here such studies. RECENT FINDINGS: interventional studies led to conflicting conclusions on the possible role of probiotics and prebiotics in allergy prevention. Two metanalyses published in 2015 did reconcile all data. Guidelines have been predicated on such studies using the GRADE methodology. SUMMARY: the guidelines for allergy prevention suggest for the first time the use of probiotics and prebiotics. The existing evidences stand for a use of such supplementation in particular for the prevention of eczema. As there is no evidence so far of superiority of one probiotic strand over the others, they should be considered as class and not as individual products. PMID- 27380593 TI - Childhood Obesity: Current Situation and Future Opportunities. AB - PURPOSE OF REVIEW: The early origins of overweight and obesity and the opportunities for early prevention are explored. RECENT FINDINGS: Overweight and obesity prevalence globally has increased at an alarming rate. No single intervention can halt the rise of the obesity epidemic. Particular attention is given to exploring causative factors and preventive measures in early life, when biological determinants of risk trajectories, feeding behaviour and dietary preferences are shaped. Some lifestyle and nutrition modifications in pregnancy and infancy can reduce subsequent obesity risk. Also postnatal infant gut colonisation may modify later obesity risk, but currently available evidence does not allow firm conclusions. Surprisingly, about 3.2 times more systematic reviews (SR) than randomized clinical trials (RCTs) were published on "probiotics" and health, and even 7.9 times more SR than RCTs on "probiotics" and obesity, which is not helpful. SUMMARY: Multiple research opportunities exist for exploring the early origins of obesity to contribute towards halting the rise in obesity prevalence. Exploring the early development of the microbiome in its complexity, its dependence on dietary and other exogenous factors, and its metabolic and regulatory functions is promising. Meaningful progress for obesity prevention can most likely be achieved by combining several strategies. PMID- 27380594 TI - Probiotics for the Management of Infantile Colic. AB - PURPOSE OF REVIEW: Evidence suggests that the gut microbiota in subjects with infantile colic differs from the gut microbiota in an unaffected population. In colicky infants, dysbiosis may affect gut motor function and gas production resulting in abdominal pain/colic. If so, it is logical to assume that manipulation of the gut microbiota may play a therapeutic role and also could be a preventive measure in the evolution of these disorders. We aimed to evaluate evidence on the effectiveness of probiotics for treating and preventing infantile colic. RECENT FINDINGS: The administration of Lactobacillusreuteri DSM 17938 is likely to reduce crying time in breastfed infants with infantile colic, but its role in formula-fed infants is less clear. Data summarized in the current review suggest that L reuteri DSM 17938 may be effective in the reduction of crying/colic both in breastfed and formula-fed infants. Other probiotics (single or in combinations) were studied in single trials only. SUMMARY: Given the lack of effective therapy for infantile colic and the good safety profile of L reuteri DSM 17938, this therapeutic option could be discussed with caregivers. Data on other probiotics, either positive or negative, are too limited to allow one to draw reliable conclusions. PMID- 27380595 TI - Probiotics for Irritable Bowel Syndrome: Clinical Data in Children. AB - PURPOSE OF REVIEW: The purpose of this review was to summarize the evidence regarding probiotics treatment for pediatric IBS. RECENT FINDINGS: The overall management of children with IBS should be tailored to the patient's specific symptoms and identifiable triggers. The four major therapeutic approaches include: pharmacologic, dietary, psychosocial, and complementary/alternative medicine interventions.Although there is limited evidence for efficacy of pharmacological therapies such as antispasmodics and anti-diarrheals, these may have a role in severe cases. A Cochrane review concluded that only weak evidence exists regarding beneficial effects of pharmacological agents in providing relief from symptoms in functional abdominal pain (AP) in children. Role of antibiotics in treatment of children with IBS remains controversial. Various non pharmacologic treatments are available for pediatric IBS. In a recent systematic review including 24 studies some evidence was found indicating beneficial effects of partially hydrolyzed guar gum (PHGG), cognitive behavioral therapy, hypnotherapy, and probiotics (LGG and VSL#3).Few randomized clinical trials (RCTs) are available in children. A meta-analysis including 9 trials which tested different probiotics as a treatment for Functional Gastrointestinal Disorders (FGIDs) in children and adolescents concluded that Lactobacillus GG, Lactobacillus reuteri DSM 17938 and VSL#3 significantly increased treatment success. We recently showed that, in children with IBS, a mixture of Bifidobacterium infantis M-63(r), breve M-16V(r) and longum BB536(r) is safe and is associated with better AP control and improved quality of life when compared to placebo. SUMMARY: Probiotics are emerging as new therapeutic tools in FGIDs, due to the recognition of the importance of gut microbiota in influencing brain gut interactions, and of the role played by intestinal infections in the genesis of AP-FGIDs. Preclinical data suggest that changes in the gut microbiota can affect brain signaling systems related to pain and associated emotional behavior. Therefore, probiotics could play a relevant role in the management of FGIDs, by affecting the gut microbiota or by altering brain function and pain perception centrally. PMID- 27380596 TI - Is There A Role for Pre-, Pro- and Synbiotics in the Treatment of Functional Constipation in Children? A Systematic Review. AB - PURPOSE OF REVIEW: To investigate the efficacy and safety of pre-, pro- and synbiotics in the treatment of pediatric functional constipation (FC). RECENT FINDINGS: A recent study reported that the gut microbiota in obese children with FC differs from that of obese children without FC. The gut microbiota may be involved in the pathophysiology of FC. Pre- and probiotics have been suggested as potential treatment modalities for FC in children. SUMMARY: PubMed and Cochrane databases were searched from inception to February 2016. We found 6 RCTs on prebiotics, 6 RCTs on probiotics and 1 RCT concerning synbiotics. Overall, most studies were at high risk of bias. The majority of studies were unable to demonstrate a significant effect of pre-, pro- or synbiotics on predefined outcome measures such as defecation frequency, fecal incontinence and painful or difficult defecation. Pre-, pro- and synbiotics were not associated with significant adverse effects. In conclusion, there is insufficient evidence to recommend pre-, pro- or synbiotics in the treatment of children with functional constipation. High-quality randomized controlled trials are warranted to further explore these treatment modalities. PMID- 27380597 TI - Early Microbe Contact and Obesity Risk: Evidence Of Causality? AB - The industrialized societies worldwide are in the middle of epidemics of diet related chronic diseases, obesity being the common denominator. Lately, these conditions have been linked with a distinct microbiota composition in affected individuals different from that of healthy individuals. In particular, dysbiosis during critical stages of development induces lasting alterations in the immune and metabolic phenotype. The compositional development of the gut microbiota, again, is highly sensitive to environmental influences such as maternal health and nutrition, the mode of delivery, early feeding and antibiotic use. Shifts in the microbiota by high-energy diet increase energy extraction and storage, provoke a low-grade inflammatory response and impair gut barrier function, and, consequently, result in obesity and metabolic disease. A lower abundance of butyrate-producing bacteria and lower overall richness of bacteria has been associated with increased metabolic disease risk in humans. Recent reports suggest that Akkermansia type bacteria or butyrate producing microbes may have anti-inflammatory potential and enhance intestinal barrier function, which may both alleviate obesity and related metabolic complications. Thus we are not directly what we eat or our mother eats, but what our microbiota eat and how the collective composition of the microbiome is modified by the diet. On this basis, altering the intestinal microecosystem may be taken as a key target to attain prophylactic or therapeutic effects in metabolic and inflammatory conditions. Tools for such modulation include specific probiotic bacteria and potentially also non-digestible carbohydrate components able to modify microbiota composition and activity. PMID- 27380598 TI - Indications and Recommendations by Societies and Institutions for the Use of Probiotics and Prebiotics in Paediatric Functional Intestinal Disorders. AB - PURPOSE OF REVIEW: To report the indications and/or recommendations by Societies and Institutions for the use of probiotics and prebiotics in functional intestinal disorders in childhood. RECENT FINDINGS: A position by Societies and Institutions is available only for infant colic, irritable bowel syndrome and constipation. Supplementation with the probiotic L reuteri DSM 17938 in breastfed term infants with colic appears to be effective in reducing crying, while still debated is its role in the prevention of colic. Irritable bowel syndrome is a common disorder in children and at present no specific treatments are available; existing data show that although high-quality studies are still needed, some evidence support the efficacy of LGG and VSL#3 in paediatric IBS. At present there is no evidence for the use of pre- or probiotics in childhood constipation. SUMMARY: Probiotics in a near future may have a definite role is some FGIDs of infants and children. The main limitations for the recommendation by Societies and Institutions are the methodological issues that limit the quality of the evidence and the heterogeneity of treatments (probiotic strain and dose, mode, dose and duration of supplementation, primary outcomes, etc). Some specific strains are promising for infant colic (L. reuteri DSM 17938) and irritable bowel syndrome (LGG) while at present there is no indication for their use in the treatment of childhood constipation. PMID- 27380599 TI - Algorithms for Common Gastrointestinal Disorders. AB - Regurgitation, infantile colic and, or, constipationare frequent during the first 12 months of life, and although they aremost of the time functional disorders, these conditions can also be related to cow's milk. Practical algorithms for their management are presented. Management consists of exclusion of warning signs for organic disease, parental reassurance and nutritional strategies. The proposed algorithms will assist healthcare providers to manage frequent gastrointestinal and cows' milkrelated symptoms in infants. PMID- 27380600 TI - Pediatric NAFLD: the Future role of Patient-Tailored Probiotics Therapy. AB - PURPOSE OF REVIEW: Clinical evidence of the use of probiotics in pediatric NAFLD, framed within gut microbiota response, is herein discussed. RECENT FINDINGS: The assistance of a new microbiological approach in probiotics' design is playing a central role in NAFLD clinical management. Experimental studies demonstrated the effect of gut microbiota manipulation in NAFLD and recent clinical evidence reported their beneficial effect in pediatric patients. SUMMARY: Epidemiology suggests that NAFLD is the most frequent pediatric chronic liver disease evolving from simple steatosis to a more severe form that may progress toward fibrosis. The goal of pharmacological treatment of NAFLD-related fibrosis is to stop and eventually to reverse liver damage, but no drug tested so far seem to be able to reach this endpoint. A few encouraging clinical studies demonstrated an improvement of hepato-metabolic milieu under probiotic treatment suggesting that they could exert an anti-fibrotic activity.Currently, new insights onto probiotics can be deduced by ad hoc generated NAFLD gut microbiota profiles. These functional maps may unveil gut ecosystem dynamics under probiotics' treatment, selecting the most appropriate for NAFLD gut microbiota amelioration. PMID- 27380601 TI - Probiotics and Prebiotics for Prevention of Food Allergy: Indications and Recommendations by Societies and Institutions. AB - Probiotics are defined as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host". Unfortunately, misuse of the term probiotic is very common. According to the regulation of the European food safety authority (EFSA) health claims on pre- and probiotics are not judged as favorable. Scientific societies should give guidance to the consumers and health care professionals on the use of probiotics and prebiotics for prevention and disease management. There is currently no positive recommendation from international scientific medical societies to use prebiotics or probiotics for treatment of food allergy or other allergic manifestations and for prevention of food allergy, allergic rhinitis, and asthma. Discrepant recommendations exist for probiotics for prevention of eczema in high risk infants. PMID- 27380603 TI - A Prospective Randomized Controlled Trial of Nonpharmacological Pain Management During Intravenous Cannulation in a Pediatric Emergency Department. AB - OBJECTIVES: Intravenous (IV) cannulation is commonly performed in pediatric emergency departments (EDs). The busy ED environment is often not conducive to conventional nonpharmacological pain management. This study assessed the use of Ditto (Diversionary Therapy Technologies, Brisbane, Australia), a handheld electronic device which provides procedural preparation and distraction, as a means of managing pain and distress during IV cannulation performed in the pediatric ED. METHODS: A randomized controlled trial with 98 participants, aged 3 to 12 years, was conducted in a pediatric ED. Participants were recruited and randomized into 5 intervention groups as follows: (1) Standard Distraction, (2) PlayStation Portable Distraction, (3) Ditto Distraction, (4) Ditto Procedural Preparation, and (5) Ditto Preparation and Distraction. Children's pain and distress levels were assessed via self-reports and observational reports by caregivers and nursing staff across the following 3 time points: (1) before, (2) during, and (3) after IV cannulation. RESULTS: Caregivers and nursing staff reported significantly reduced pain and distress levels in children accessing the combined preparation and distraction Ditto protocol, as compared to standard distraction (P <= 0.01). This intervention also saw the greatest reduction in pain and distress as reported by the child. CONCLUSIONS: Caregiver reports indicate that using the combined Ditto protocol was most effective in reducing children's pain experiences while undergoing IV cannulation in the ED. The use of Ditto offers a promising opportunity to negotiate barriers to the provision of nonpharmacological approaches encountered in the busy ED environment, and provide nonpharmacological pain-management interventions in pediatric EDs. PMID- 27380602 TI - Clinical characteristics and outcome of cirrhotic patients with high protein concentrations in ascites: a prospective study. AB - BACKGROUND: The protein concentration in ascites is usually low in cirrhosis because capillarization and defenestration of the sinusoids limit diffusion of large proteins from plasma to the space of Disse. However, some cirrhotic patients have high-protein ascites (HPA). AIM: The aim of this study was to describe and compare the characteristics and prognosis between cirrhotic patients with HPA (>20 g/l) and patients with low-protein ascites (LPA). PATIENTS AND METHODS: In this longitudinal observational prospective cohort study, all consecutive cirrhotic patients with ascites hospitalized in our tertiary liver center were included and followed for up to 2 years, provided that they had no other cause of HPA. HPA was defined as protein concentrations of more than 20 g/l. RESULTS: Among 107 patients included, 19 (17.8%) had HPA. HPA patients had more refractory ascites (63 vs. 34%), better liver functions, and a higher 1-year transplant-free survival rate compared with LPA patients (P<0.05). Portal hypertension parameters were not different. During follow-up, 47% of HPA patients were treated by transjugular intrahepatic portosystemic shunts versus 18% of LPA patients, whereas 15 LPA patients required liver transplantation for end-stage liver disease versus only one HPA patient. We observed higher protein filtration and less pericellular, centrilobular, and sinusoidal fibrosis in cirrhotic HPA livers compared with LPA livers. CONCLUSION: Almost 20% of cirrhotic patients with ascites have HPA (>20 g/l). These patients have better liver functions and a higher 1-year survival than those with LPA, even though ascites are more often refractory. PMID- 27380604 TI - Traumatic Pulmonary Herniation at the Diaphragmatic Junction in a Pediatric Patient: A Rare Complication of Blunt Chest Trauma. AB - We present a case of traumatic intercostal pulmonary herniation in an 11-year-old boy after blunt trauma to the chest, without associated chest wall disruption or pneumothorax. This condition is especially uncommon in children, with only 5 previously reported cases and most occurring after penetrating chest trauma. To date, there are no reports in literature describing traumatic intercostal lung herniation at the diaphragmatic junction with a closed chest cavity in a child. The number of traumatic lung herniation diagnoses may be expanded by a more liberal use of computed tomography when serious injury is suspected. Computed tomography and advanced imaging should be considered in pediatric trauma patients presenting with concern for intrathoracic injury that may not be seen on plain film. Traumatic blunt intrathoracic and intra-abdominal injuries in the pediatric population that are within proximity of diaphragmatic insertion should be thoroughly evaluated to rule out diaphragmatic injury. As in our case, invasive surgical intervention such as thoracoscopy may be necessary. PMID- 27380606 TI - Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in the Pediatric Population: A Review. PMID- 27380605 TI - Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in the Pediatric Population: A Review. AB - Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe dermatologic reactions with mucocutaneous involvement that carry elevated mortality rates. They differ along a spectrum of severity based upon body surface area affected. These conditions, usually caused by a drug or infection, are believed to result from cell-mediated and often drug-specific cytotoxic reactions against keratinocytes, leading to widespread dermal-epidermal detachment. Studies attempting to identify potential curative therapies such as intravenous immune globulin (IVIG) and corticosteroids remain inconclusive. However, improved outcomes have been demonstrated by early withdrawal of offending medications, early transfer to an intensive care unit or burn unit, and aggressive supportive care. Due to the rare incidence of SJS and TEN, its recurrence among survivors hints at future vulnerability for these patients, and notorious offending medications should thus be avoided. This clinical review will highlight the diagnostic and therapeutic challenges posed by SJS and TEN, while emphasizing the need to maintain them high on the emergency medicine physician's differential. The review will also detail the supportive measures to take for preventing the rapid progression of mucocutaneous complications and subsequent sepsis-related mortality. PMID- 27380607 TI - Essentials of Pediatric Emergency Medicine Fellowship: Part 3: Clinical Education and Experience. AB - This article is the third in a 7-part series that aims to comprehensively describe the current state and future directions of pediatric emergency medicine fellowship training from the essential requirements to considerations for successfully administering and managing a program to the careers that may be anticipated upon program completion. This article focuses on the clinical aspects of fellowship training including the impact of the clinical environment, modalities for teaching and evaluation, and threats and opportunities in clinical education. PMID- 27380608 TI - Point-Of-Care Ultrasound Findings Associated With Foreign Body Aspiration in the Pediatric Emergency Department. AB - Point-of-care ultrasound (POCUS) continues to generate new and interesting clinical findings as its use expands in the pediatric emergency department. This case report describes the novel findings identified during a POCUS focused lung examination of a pediatric patient with suspected foreign body aspiration. PMID- 27380609 TI - Diagnosis of a Peritonsillar Abscess by Transcutaneous Point-of-Care Ultrasound in the Pediatric Emergency Department. AB - We report a case of a pediatric patient with an initial diagnosis of peritonsillar cellulitis made by otolaryngology. The findings from a subsequent transcutaneous point-of-care ultrasound by a pediatric emergency physician directly affected the decision to perform needle aspiration. Sonographic characteristics of a peritonsillar abscess may be helpful in the prompt diagnosis of peritonsillar abscess. PMID- 27380610 TI - Torsed Meckel Diverticulum Mimicking a Cystic Teratoma. PMID- 27380611 TI - ECGs in the ED. PMID- 27380612 TI - Intravascular (blood vessel) histiocytosis with haemophagocytosis. AB - AIMS: Many types of intravascular lymphohistiocytic proliferation have been described recently; this was previously an unnoticed or misinterpreted phenomenon. Intralymphatic lymphohistiocytic aggregates are relatively common, and include benign, malignant and indeterminate conditions. In contrast, all non endothelial proliferations in the lumina of blood vessels have been interpreted so far as malignant. Herein, we present three cases of histiocytic proliferations in the lumen of blood vessels associated with intracytoplasmic granulocyte debris (haemophagocytosis), a previously undescribed entity. METHODS AND RESULTS: We identified three patients from two institutions with similar cutaneous lesions, both clinically and microscopically. Information regarding clinical history, histological features and immunoprofiles were obtained. The three cases presented intravascular histiocytosis with haemophagocytosis involving blood vessels of the dermis, a process that may be representative of a new entity. The patients were two women and one man who presented a symmetrical reticulated erythema with a tendency to involve the skin of the breasts. The lesions were indolent, did not ulcerate and followed a benign course. CONCLUSION: This seemingly novel condition is characterized by the presence of histiocytic cells inside blood vessels, where they have not been described previously as an entity. The most reasonable explanation for this process is an origin from the non-classical subset of monocytes that 'patrol' the inner face of blood vessels acting as macrophages. The existence of this entity should be kept in mind to avoid overdiagnosis of malignancy. PMID- 27380613 TI - Environmentally-Safe Conditions for a Palladium-Catalyzed Direct C3-Arylation with High Turn Over Frequency of Imidazo[1,2-b]pyridazines Using Aryl Bromides and Chlorides. AB - Pd(OAc)2 was found to catalyze very efficiently the direct arylation of imidazo[1,2-b]pyridazine at C3-position under a very low catalyst loading and phosphine-free conditions. The reaction can be performed in very high TOFs and TONs employing as little as 0.1-0.05 mol % catalyst using a wide range of aryl bromides. In addition, some electron-deficient aryl chlorides were also found to be suitable substrates. Moreover, 31 examples of the cross couplings were reported using green, safe, and renewable solvents, such as pentan-1-ol, diethylcarbonate or cyclopentyl methyl ether, without loss of efficiency. PMID- 27380614 TI - The Effects of Preoperative Endoscopic Tattooing on Distal Surgical Margin and Ileostomy Rates in Laparoscopic Rectal Cancer Surgery: A Prospective Randomized Study. AB - AIM: This study aimed to evaluate the effect of endoscopic marking on the distal surgical margin and ileostomy rates in laparoscopic rectal cancer surgery. MATERIALS AND METHODS: Forty patients, who underwent surgery between September 2012 and December 2013 for rectal cancer limited to or with invasion of the upper rectum, were included in the study. The distal tumor margin was marked with purified carbon particles by colonoscopy before surgery in one group (n=20); no marking was performed in the second group (n=20). Patients were assigned randomly to each group. Laparoscopic anterior or low-anterior resection was performed in all patients. Demographic and operative data, pathology results, morbidity, and ileostomy rates were measured. RESULTS: There was no statistically significant difference in the demographic data, the tumor size, the amount of bleeding, the specimen length, the harvested lymph node number, postoperative complications, the length of hospital stay, rehospitalization, and the operation duration between groups 1 and 2, respectively. The distal surgical margin was significantly shorter in the marked group. The protective ileostomy rates were also lower in the marked group; however, the difference did not reach statistical significance. CONCLUSIONS: Preoperative endoscopic tattooing decreases distal resection margins and may reduce protective ileostomy rates in laparoscopic rectal surgery. PMID- 27380615 TI - Efficacy of Repeated Intraperitoneal Administration of Levobupivacaine in Pain and Opioid Consumption After Elective Laparoscopic Cholecystectomy: A Prospective Randomized Placebo-controlled Trial. AB - PURPOSE: To estimate the effect of intraperitoneal levobupivacaine on postoperative pain and analgesic requirements, during the first 24 hours after elective laparoscopic cholecystectomy (LC). MATERIALS AND METHODS: In this prospective, randomized, placebo-controlled study, 73 consecutive patients scheduled for LC were randomized into 2 groups. In the local anesthetic group 36 patients received 10 mL of 0.5% levobupivacaine intraperitoneally at the end of the LC and at 4 hours postoperatively, whereas in the placebo group 37 patients received 10 mL of 0.9% normal saline. Visual analog scale pain scores, analgesic consumption, side-effects, and vital signs were recorded for 24 hours postoperatively. RESULTS: In the local anesthetic group lower visual analog scale pain scores were observed postoperatively, both at rest and at movement (P-values compared with placebo, 0.012 and <0.001, respectively). Fentanyl consumption was greater in the placebo group (P-value <0.001). CONCLUSIONS: Intraperitoneal administration of 10 mL 0.5% levobupivacaine after LC is effective in reducing postoperative pain and decreasing opioid consumption. PMID- 27380616 TI - Comparison of the Effect of Instrument Type on Transanal Endoscopic Surgery Learning Curves. AB - BACKGROUND: Transanal endoscopic surgery (TES) can be technically difficult due to the constraints of operating through a narrow proctoscope channel. In this study, we compared the performance of surgical novices using instruments with and without articulating shafts to perform a simulated TES task. METHODS: Medical students each performed 10 repetitions of the Fundamentals of Laparoscopic Surgery circle-cut task. Participants were randomized into 3 groups: 2 performed the task through a TES proctoscope using scissors with either a rigid (TES-R) or articulating (TES-A) shaft. The third group performed the task laparoscopically (LAP). RESULTS: A total of 31 medical students participated. The LAP group had a faster mean task time than both the TES-R and TES-A groups (LAP 201+/-120 s vs. TES-R 362+/-212 s and TES-A 405+/-212 s, both P <0.001). The TES-R group made more errors (ie, deviation from a perfect circle) than both the other groups. The TES-R group adjusted the proctoscope position during more repetitions than the TES-A group. CONCLUSIONS: Students had faster task times when operating laparoscopically than through a TES protoscope. Task times were similar between the TES groups using scissors with articulating and rigid shafts; however, use of the articulating instruments resulted in fewer errors and less need to adjust proctoscope position. PMID- 27380617 TI - Noble-Metal-Free Photocatalytic H2 Generation: Active and Inactive 'Black' TiO2 Nanotubes and Synergistic Effects. AB - Over the past five years a number of different synthesis approaches has been reported to obtain so-called 'black' titania. One of the outstanding features of the material is that certain synthesis processes lead to the formation of an intrinsic co-catalytic center and thus enable noble-metal free photocatalytic H2 generation. In the present work, using TiO2 nanotube layers, we compare three common 'blackening' approaches, namely i) the original high-pressure hydrogenation (HPT-H2 ), ii) a classic high temperature reduction in Ar, and iii) an electrochemical (cathodic) reduction. We demonstrate that except for high pressure hydrogenation also cathodic reduction leads to an activation of TiO2 - that is, it exhibits noble-metal-free photocatalytic H2 generation. Moreover, we show that a combination of cathodic reduction/high pressure hydrogenation leads to a synergistic effect, that is, a significant enhancement of the combined co catalytic activity. PMID- 27380618 TI - A Survey of Hospitals That Participated in a Statewide Collaborative to Implement and Sustain Rapid Response Teams. AB - OBJECTIVES: To determine the level of sustainability of rapid response teams (RRTs) among a group of hospitals that participated in a statewide collaborative to implement and sustain RRTs. SETTING AND SAMPLE: Fifty-six hospitals located in a southeastern state in the United States participated in a statewide 9-month collaborative that provided organization leaders with resources to implement and sustain RRTs. Thirty-three of these hospitals completed the electronic survey. Two hospitals were excluded because of missing data. MEASUREMENT: The RRT Institutionalization Scale (RRT-IS), adapted from the Level of Institutionalization Scale, measured the degree of institutionalization (i.e., passages, routines, and niche saturation) across four subsystems: production, maintenance, supportive, and managerial. RESULTS: Thirty-one hospitals participated (response rate 55%). Rapid response team sustainability levels ranged from 1.0 to 5.98 (mean = 3.78, 95% CI = 3.40-4.17). The highest sustainability score was reported in the managerial subsystem (median = 5.3, IQR = 4.5-7.33), and the lowest score was reported in the supportive subsystem (median = 1.0, IQR = 1.0-2.0). CONCLUSIONS: Rapid response team sustainability levels varied across hospitals in the collaborative. Different levels of sustainability were also observed across organizational subsystems. The lack of resources, staff, and dedicated funds hampered organizations' sustainability efforts. PMID- 27380619 TI - Anti-ulcerogenic effect of cavidine against ethanol-induced acute gastric ulcer in mice and possible underlying mechanism. AB - Cavidine, a major alkaloid compound isolated from Corydalis impatiens, has various pharmacological effects but its effect on gastric ulcer has not been previously explored. The current study aimed to investigate the possible anti ulcerogenic potential of cavidine in the model of ethanol-induced gastric ulcer. Mice received cavidine (1, 5 or 10mg/kg, ig), cimetidine (CMD, 100mg/kg, ig) or vehicle at 12h and 1h before absolute ethanol administration (0.5mL/100g), and animals were euthanized 3h after ethanol ingestion. Gross and histological gastric lesions, biochemical, immunological and Western blot parameters were taken into consideration. The results showed that ethanol administration produced apparent mucosal injuries with morphological and histological damage, whereas cavidine pre-treatment reduced the gastric injuries. Cavidine pre-treatment also ameliorated the contents of malonaldehyde (MDA) and myeloperoxidase (MPO) activity, and increased the mucosa levels of glutathione (GSH), superoxide dismutase (SOD) and prostaglandin E2 (PGE2), relative to the model group. Also cavidine was able to decrease the levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), inhibit the up-regulation of cyclo-oxygenase-2 (COX-2) expression and activation of Nuclear factor-kappa B (NF-kappaB) pathway. Taken together, these results indicated that cavidine exerts a gastroprotective effect against gastric ulceration, and the underlying mechanism might be associated with the stimulation of PGE2, reduction of oxidative stress, suppression of NF-kappaB expression and subsequent reduced COX-2 and pro inflammatory cytokines. PMID- 27380620 TI - Immunotherapeutic effects of cytokine-induced killer cells combined with CCL21/IL15 armed oncolytic adenovirus in TERT-positive tumor cells. AB - The effective antitumor immune responses are dependent on coordinate interaction of various effector cells. Thus, the combination of adoptive immunotherapy and target gene therapy is capable of efficiently generating a productive antitumor immune response. We investigated whether combination of cytokine-induced killer (CIK) cells adoptive immunotherapy and CCL21/IL15 armed oncolytic adenovirus could induce the enhanced antitumor activity. The CCL21/IL15 co-expression oncolytic adenoviruses were constructed by using the AdEasy system, which uses homologous recombination with shuttle plasmids and full length Ad backbones. This conditionally replicating adenoviruses CRAd-CCL21-IL15 could induce apoptosis in TERTp-positive tumor cells for viral propagation, but do not replicate efficiently in normal cells, because the E1A promoter was replaced by telomerase reverse transcriptase promoter (TERTp). Our results showed that the combination of CIK cells and CRAd-CCL21-IL15 could induce higher antitumor activity than either CIK cells or CRAd-CCL21-IL15 alone. This combined treatment could induce the tumor specific cytotoxicity of CTLs (cytotoxic T lymphocytes) in vitro. Moreover, the treatment of established tumors with the combined therapy of CIK cells and CRAd-CCL21-IL15 resulted in tumor regression. This study suggests that the combined treatment by adoptive immunotherapy and gene therapy is a promising strategy for the therapy of tumor. PMID- 27380621 TI - The effects of payoff manipulations on temporal bisection performance. AB - There is growing evidence that alterations in reward rates modify timing behavior demonstrating the role of motivational factors in interval timing behavior. This study aimed to investigate the effects of manipulations of rewards and penalties on temporal bisection performance in humans. Participants were trained to classify experienced time intervals as short or long based on the reference durations. Two groups of participants were tested under three different bias conditions in which either the relative reward magnitude or penalty associated with correct or incorrect categorizations of short and long reference durations was manipulated. Participants adapted their choice behavior (i.e., psychometric functions shifted) based on these payoff manipulations in directions predicted by reward maximization. The signal detection theory-based analysis of the data revealed that payoff contingencies affected the response bias parameter (B") without altering participants' sensitivity (A') to temporal distances. Finally, the response time (RT) analysis showed that short categorization RTs increased, whereas long categorization RTs decreased as a function of stimulus durations. However, overall RTs did not exhibit any modulation in response to payoff manipulations. Taken together, this study provides additional support for the effects of motivational variables on temporal decision-making. PMID- 27380622 TI - Finding the positive in all of the negative: Facilitation for color-related emotion words in a negative priming paradigm. AB - A study conducted by Sutton and Altarriba (2008) suggested that color-related emotion words (e.g., sad, envy) produce standard Stroop interference effects. Associations between emotion words and colors are culture specific, and may be the result of common phrases in a language (e.g., "feeling blue" in English), or a result of the manner in which color is used to signify information or meaning in a language (e.g., red often represents threat). In the present paper, the same stimuli were investigated in a negative priming paradigm in which participants were asked to name the ink color of a presented word. In this task, response times are typically slower in ignored repetition trials (i.e., the probe target is related to the prime distractor) than control trials. The results of Experiment 1 indicated that color words and color-related neutral words yielded negative priming; however, color-related emotion words yielded significant facilitation. In Experiment 2, the three word types were intermixed within the same block and the same results were obtained. The current study provides converging evidence that salient distractors cannot be ignored. PMID- 27380623 TI - Spectroscopic study of 3-Hydroxyflavone - protein interaction in lipidic bi layers immobilized on silver nanoparticles. AB - The interaction of 3-Hydroxyflavone with serum proteins (BSA and HSA) in lecithin lipidic bi-layers (PC) immobilized on silver nanoparticles (SNPs), was studied by fluorescence and Raman spectroscopy. BSA secondary structure was quantified with a deconvolution algorithm, showing a decrease in alpha-helix structure when lipids were added to the solution. The effect of temperature on the rate of the excited-state intra-molecular proton transfer and on the dual fluorescence emission of 3-HF in the HSA/PC/SNPs systems was discussed. Evaluation of the antioxidant activity of 3-HF in HSA/PC/SNPs systems was also studied. The antioxidant activity of 3-HF decreased in the presence of SNPs. The results are discussed with relevance to the secondary structure of proteins and of the 3-HF based nano-systems to a topical formulation useful in the oxidative stress process. PMID- 27380624 TI - Impact of a Delayed Laparoscopic Appendectomy on the Risk of Complications in Acute Appendicitis: A Retrospective Study of 4,065 Patients. AB - BACKGROUND: Urgent surgery performed for appendicitis is hypothesized to avoid complications such as perforation or abscess. This study aimed to evaluate the effect of the timing of surgery on the complications of laparoscopic appendectomy. METHODS: A retrospective review of 4,065 patients who underwent a laparoscopic appendectomy was conducted. The demographic data, time of presentation, physical findings, diagnostic data and complications were recorded. The patients were divided into 4 groups (Group A, 0-6 h; Group B, 6-12 h; Group C, 12-18 h; Group D, over 18 h) based on the time elapsed from the evaluation at the emergency room to the appendectomy. RESULTS: Group A consisted of 2,084 (51.3%) patients, Group B consisted of 1,553 (38.2%) patients, Group C consisted of 388 (9.5%) patients and Group D consisted of 40 (1.8%) patients. A perforated appendicitis was observed in 560 (13.8%) patients. Postoperative complications developed in 293 (7.2%) patients. No significant differences in perforation and postoperative complications were observed between the 4 groups. CONCLUSION: The timing of surgery did not affect the incidence of complications or perforated appendicitis. PMID- 27380625 TI - Delay in disclosure of non-parental child sexual abuse in the context of emotional and physical maltreatment: A pilot study. AB - The present pilot study sought to identify predictors of delays in child sexual abuse (CSA) disclosure, specifically whether emotional and physical abuse by a parental figure contributes to predicting delays over and above other important victim factors. Alleged CSA victims (N=79), whose parental figures were not the purported sexual abuse perpetrators, were interviewed and their case files reviewed, across two waves of a longitudinal study. Regression analyses indicated that experiencing both emotional and physical abuse by a parental figure was uniquely predictive of longer delays in disclosure of CSA perpetrated by someone other than a parental figure. Victim-CSA perpetrator relationship type and sexual abuse duration also significantly predicted CSA disclosure delay, whereas victim age at the time of the police report, victim gender, and victims' feelings of complicity were not significant unique predictors. Child abuse victims' expectations of lack of parental support may underlie these findings. Parent child relationships are likely crucial to timely disclosure of CSA, even when a parent is not the CSA perpetrator. PMID- 27380626 TI - Identifying Specific Clinical Symptoms of Behavioral Variant Frontotemporal Dementia Versus Differential Psychiatric Disorders in Patients Presenting With a Late-Onset Frontal Lobe Syndrome. AB - OBJECTIVE: Early differentiation between psychiatric disorders and behavioral variant frontotemporal dementia (bvFTD) is of paramount importance in patients with the late-onset frontal lobe syndrome. As bvFTD in patients will deteriorate, psychiatric disorders are treatable. To date, misdiagnosis often occurs due to an overlap of symptoms and lack of specific biomarkers. The aim of our study was to investigate whether specific symptoms could separate bvFTD from psychiatric disorders. METHODS: In a naturalistic, prospective, multicenter study, 137 patients (aged 45-75 years, 72% male) with a late-onset frontal lobe syndrome were included based on their scores on the Frontal Behavioral Inventory (FBI) and the Stereotypy Rating Inventory (SRI) from April 2011 to June 2013. In a multidisciplinary consensus meeting, diagnoses were established based on elaborate neuropsychological testing, magnetic resonance imaging, fludeoxyglucose F 18 positron emission tomography, cerebrospinal fluid biomarkers, and clinical examination by a neurologist and a psychiatrist based on the International bvFTD Criteria Consortium for bvFTD and DSM-IV-TR criteria for psychiatric disorders. RESULTS: Forty-four subjects (32.8%) were diagnosed with a psychiatric disorder, 10 (7.3%) with possible bvFTD, and 45 (32.8%) with probable bvFTD. A logistic regression analysis was performed with "psychiatry or bvFTD" as dependent variable and clinical variables (Montgomery-Asberg Depression Rating Scale [MADRS], SRI, FBI) and demographics as independent variables. A positive history of psychiatric illness, male gender, lower SRI scores and higher MADRS scores were predictive of psychiatric disorders, explaining 65.2% of the variance in diagnosis of psychiatry versus bvFTD (chi25 = 60.04, P < .001). On the FBI, symptom level verbal apraxia/aphasia and impulsivity were predictive of bvFTD, whereas irritability was predictive of psychiatric disorders. CONCLUSIONS: In daily clinical practice, specific subtyping of clinical symptoms in patients with late-onset frontal lobe syndrome may aid in differentiating bvFTD patients from psychiatric patients and may provide guidance in patient management. PMID- 27380627 TI - TLR2 and TLR4 co-activation utilizes distinct signaling pathways for the production of Th1/Th2/Th17 cytokines in neonatal immune cells. AB - Co-activation of TLR2 and TLR4 by gram negative and gram positive bacterial ligands induces a robust pro-inflammatory response in inflammatory cells. In order to understand the signaling mechanism, we aimed to delineate the signaling molecules involved in TLR2 and TLR4 co-activation in neonatal immune cells for the production of Th1/Th2/Th17 inflammatory cytokines. For this, we pretreated cord blood and peripheral blood mononuclear and human mast cells with specific signaling molecule inhibitors such as BAY117082, PD98059 and LY294002 and then stimulated with LPS and PGN and assayed for cytokines IL-6, IL-12/IL-23p40 (Th1), IL-13 (Th2), IL-23 (Th17) and RANTES secretion. We found that upon co-stimulation the phosphorylation of NFkappaBp65, ERK1/2 and Akt was found to be higher than when stimulated with individual ligands in CBMCs. Also, when compared to adult cells, neonatal cells were more potent in the activation of ERK and Akt through TLR2 and TLR4 co-activation. In addition, neonatal cells possess similar capacity to activate NFkappaB as that of adult cells for IL-6 secretion. Furthermore, all three signaling molecules were found to be involved in the production of Th17 cytokines which is detrimental during inflammation induced by infection in neonates whereas NFkappaB is mainly involved in the induction of pro-inflammatory response and Th2 cytokines production. In conclusion, different signaling molecules were utilized for the production of different cytokines in immune cells. PMID- 27380629 TI - Amycolatopsis albispora sp. nov., isolated from deep-sea sediment. AB - A novel Gram-stain-positive, aerobic, non-motile actinobacterium, designated strain WP1T, was isolated from a deep-sea sediment sample collected from the Indian Ocean, and examined in a taxonomic study using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain WP1T formed a distinct phyletic lineage in the genus Amycolatopsis and was closely related to A. magusensis KT2025T (97.8 % 16S rRNA gene sequence similarity), A. palatopharyngis 1BDZT (97.3 %) and A. marinaMs392AT (97.2 %). The isolate grew at 4-45 degrees C, pH 5-11 and in the presence of 0-8 % (w/v) NaCl. The cell wall of the novel strain contained meso-diaminopimelic acid and arabinose and galactose as the diagnostic sugars. Major fatty acids identified were iso-C16 : 0, C17 : 1omega8c and C17 : 1omega6c. The predominant menaquinones were MK-9(H4) and MK-7. The polar lipids detected were phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylmethylethanolamine, four unknown phospholipids and one unknown glycolipid. The genomic DNA G+C content was 72.2 mol%. Strain WP1T displayed low DNA-DNA reassociation with A. magusensis DSM 45510T (mean value 36.2 %), A. palatopharyngis JCM 12460T (31.5 %) and A. marina JCM 16121T (29.7 %). Based on the data reported here, strain WP1T represents a novel species within the genus Amycolatopsis, for which the name Amycolatopsis albisporasp. nov. is proposed. The type strain is WP1T (=KCTC 39642T=MCCC 1A10745T). PMID- 27380628 TI - Regulation of distinct branches of the non-canonical Wnt-signaling network in Xenopus dorsal marginal zone explants. AB - BACKGROUND: A tight regulation of the Wnt-signaling network, activated by 19 Wnt molecules and numerous receptors and co-receptors, is required for the establishment of a complex organism. Different branches of this Wnt-signaling network, including the canonical Wnt/beta-catenin and the non-canonical Wnt/PCP, Wnt/Ror2 and Wnt/Ca(2+) pathways, are assigned to distinct developmental processes and are triggered by certain ligand/receptor complexes. The Wnt signaling molecules are closely related and it is still on debate whether the information for activating a specific branch is encoded by specific sequence motifs within a particular Wnt protein. The model organism Xenopus offers tools to distinguish between Wnt-signaling molecules activating distinct branches of the network. RESULTS: We created chimeric Wnt8a/Wnt11 molecules and could demonstrate that the C-terminal part (containing the BS2) of Wnt8a is responsible for secondary axis formation. Chimeric Wnt11/Wnt5a molecules revealed that the N terminus with the elements PS3-1 and PS3-2 defines Wnt11 specificity, while elements PS3-1, PS3-2 and PS3-3 are required for Wnt5a specificity. Furthermore, we used Xenopus dorsal marginal zone explants to identify non-canonical Wnt target genes regulated by the Wnt5a branch and the Wnt11 branch. We found that pbk was specifically regulated by Wnt5a and rab11fip5 by Wnt11. Overexpression of these target genes phenocopied the overexpression of their regulators, confirming the distinct roles of Wnt11 and Wnt5a triggered signaling pathways. Furthermore, knock-down of pbk was able to restore convergent extension movements in Wnt5a morphants. CONCLUSIONS: The N-terminal part of non-canonical Wnt proteins decides whether the Wnt5a or the Wnt11 branch of the Wnt-signaling network gets activated. The different non-canonical Wnt branches not only regulate cellular behavior, but, surprisingly, also regulate the expression of different target genes. One of these target genes, pbk, seems to be the relevant target gene executing Wnt5a-mediated regulation of convergent extension movements. PMID- 27380630 TI - Contribution of Sudanese medical diaspora to the healthcare delivery system in Sudan: exploring options and barriers. AB - BACKGROUND: Medical diaspora options, including the engagement of expatriate physicians in development efforts within their home country, are being called for to reverse the effects of brain drain from developing countries. This paper presents the results of a study exploring the potential contributions for the Sudanese Medial Diaspora Options to the healthcare delivery system (HCDS) in Sudan, focusing on the options of temporal and permanent returns and the likely obstacles faced in their implementation. METHODS: This was a cross-sectional study using a mixed methods design including quantitative and qualitative approaches. For the quantitative approach, the study, which focused on the possible contribution of the diaspora to healthcare delivery in Sudan, was based on an online survey using random purposive and snowballing sampling techniques involving 153 Sudanese physicians working in Saudi Arabia and other Gulf States, the United Kingdom, the Republic of Ireland, and the United States of America. The qualitative approach involved in-depth interviews with returnee physicians and key informants in Sudan, focusing on the return experiences, the barriers for return, and the options to improve future contributions. RESULTS: Despite contributions of the Sudanese medical diaspora being of a small scale considering the size of the phenomenon, as well as infrequent and not appropriately organized, their inputs to academia and the links built with overseas institutions and specialist clinical services were nevertheless remarkable. The main barrier to temporal return was inappropriate organization by the local counterparts, while those for permanent return of physicians were poor work environment, insufficient financial payment, unsecured accommodation, and offspring education. The study identified short-term return as a feasible option considering the country's current conditions. Proper coordination mechanisms for short-term returns and facilitation of permanent return through stakeholders' collaboration were proposed to improve diaspora contributions. CONCLUSIONS: The potentials of Sudanese medial diaspora contributions to the HCDS in Sudan are promising. Short-term contributions were observed as the best option for the current country situation. Creation of a coordinating body from within the healthcare sector in Sudan to effectively coordinate diaspora contributions is recommended. PMID- 27380631 TI - Medicinal plants sold at traditional markets in southern Ecuador. AB - BACKGROUND: The traditional markets in southern Ecuador and within the Andean region are especially important for plant resource trading among local people, even since before Spanish colonization; therefore, ethnobotanical studies are currently necessary and important. These strategic spaces persist for the traditional medicine cultural value reflected in the higher consumption of medicinal plants, which span all socioeconomic levels of rural and urban people. The purpose of this study includes the following: 1) to create a novel list of medicinal plants sold at 33 traditional markets; 2) to establish medicinal plant use agreement amongst vendors with the Factor of Informant Consensus (FIC); and 3) to determine the most sold medicinal plant species using the Fidelity Level (FL). METHODS: This study focus on traditional markets ethnobotany utilizes the largest sample of medicinal plants market vendors up to date in Ecuador, interviewing them at 33 traditional markets, located within the Loja province. In order to determine the most sold medicinal plants and their ethnobotanical information, structured questionnaires and personal conversations were conducted with 196 medicinal plant vendors, and voucher specimens were created. Agreement among vendors about the therapeutic use of medicinal plants was measured using the FIC, and the most sold medicinal plant species were assessed with the FL. RESULTS AND DISCUSSION: This research registered 160 medicinal plant species, grouped in 126 genera and 57 families that were sold in 33 traditional markets. The uses of medicinal plants in southern Ecuador are related to a long history of traditional medicine health practices that has persisted until today as well as high plant diversity. The 53 therapeutic uses recorded were grouped into 12 medical categories that were adapted from the World Health Organization. Three medical categories shared the highest value for FIC = 0.92, which showed a high level of agreement of market vendors for 57 medicinal plant species sold to treat ailments related with digestive, dermatological, and sensorial systems. The FL index determined 11 culturally important medicinal plant species based on the reported uses by 40 or more market vendors. Two medicinal plant species had an FL = 100 %, Matricaria recutita and Gaiadendrum punctatum, used to treat digestive and respiratory systems ailments. CONCLUSIONS: In the Loja province, people continue to consume medicinal plant species sold at local markets to treat somatic and/or psychosomatic health ailments because sociocultural customs are strongly expressed in ancestral practices of wellbeing. When the largest values of FL (60.5 %-100 %) and FIC (0.81-0.92) indexes are combined, they demonstrated agreement among 196 market vendors in the use of seven medicinal plant species that were most sold for the 12 medical categories. This study stresses how important public policies are for the trade and quality of medicinal plant resources, particularly for local people practicing auto-medication. Reasons for the maintenance of traditional markets in southern Ecuador include lower cost of medicinal plants, confidence in traditional medicine, and/or sociocultural environment. In Ecuador, the sustainable management of wild medicinal plants diversity, particularly the most sold, is crucial for its conservation in nature. PMID- 27380632 TI - Development of a lateral flow immunochromatographic assay for the rapid diagnosis of Orf virus infections. AB - A rapid and simple lateral-flow immunochromatographic assay (LFIA) was developed for the specific detection of Orf virus (ORFV) using two distinct monoclonal antibodies (MAbs: 5A5 and 6F2) against the ORFV ORF011 protein. The MAb 5A5 was conjugated with colloidal gold, and the MAb 6F2 and goat anti-mouse IgG were sprayed onto a nitrocellulose membrane in strips at positions designated test (T) and control (C), respectively. The results showed that samples of ORFV complexed with colloidal gold-conjugated MAb 5A5, were captured by MAb 6F2 at the T line resulting in the appearance of a purple band. When samples did not contain ORFV or when they contained a quantity of ORFV below the detection limit of the test, only the C line was visible. The analysis of sensitivity of the test demonstrated that the lowest detected quantity of ORFV was 2.03*10(3.0) TCID50/ml. Storage at room temperature for 6 months did not result in the loss of performance of the LFIA test. Using loop-mediated isothermal amplification (LAMP) as a reference test, the relative specificity and sensitivity of the LFIA test were determined to be 100% and 92.1%, respectively. Based on these results, the LFIA test developed may be a suitable tool for rapid on-site testing for ORFV infection. PMID- 27380633 TI - Sulfur dioxide: a physiologic endothelium-derived relaxing factor. AB - The gasotransmitter nitric oxide was classified as the first endothelium-derived relaxant factor, and opened a new era in cardiovascular research. Another small gas, sulfur dioxide (SO2), can also be generated endogenously in mammals. Recent studies have shown that SO2 may play important roles in the cardiovascular system. At low concentrations, the vasodilatory effect of SO2 is endothelium dependent. The vasodilation induced by an endothelium-derived relaxant factor is achieved by the opening of potassium channels, and hyperpolarization of the membranes of vascular smooth muscle cells. This feature is in accordance with that of SO2. The vasodilatory effect of SO2 is related to the opening of adenosine triphosphate-sensitive potassium channels and high-conductance calcium activated potassium channels. The 3'-5'-cyclic guanosine monophosphate pathway and activation of nitric oxide synthase are also involved in the endothelium derived relaxant factor effect of SO2. The vasodilatory effect of gaseous SO2 is much stronger than that of its derivatives (bisulfite and sulfite). It is suggested that SO2 may be a candidate endothelium-derived relaxant factor, which could lead to a new era of research into cardiovascular disease in mammals. PMID- 27380634 TI - Hierarchical bioceramic scaffolds with 3D-plotted macropores and mussel-inspired surface nanolayers for stimulating osteogenesis. AB - The hierarchical structure of biomaterials plays an important role in the process of tissue reconstruction and regeneration. 3D-plotted scaffolds have been widely used for bone tissue engineering due to their controlled macropore structure and mechanical properties. However, the lack of micro- or nano-structures on the strut surface of 3D-plotted scaffolds, especially for bioceramic scaffolds, limits their biological activity. Inspired by the adhesive versatility of mussels and the active ion-chelating capacity of polydopamine, we set out to prepare a hierarchical bioceramic scaffold with controlled macropores and mussel-inspired surface nanolayers by combining the 3D-plotting technique with the polydopamine/apatite hybrid strategy in order to synergistically accelerate the osteogenesis and angiogenesis. beta-Tricalcium phosphate (TCP) scaffolds were firstly 3D-plotted and then treated in dopamine-Tris/HCl and dopamine-SBF solutions to obtain TCP-DOPA-Tris and TCP-DOPA-SBF scaffolds, respectively. It was found that polydopamine/apatite hybrid nanolayers were formed on the surface of both TCP-DOPA-Tris and TCP-DOPA-SBF scaffolds and TCP-DOPA-SBF scaffolds induced apatite mineralization for the second time during the cell culture. As compared to TCP scaffolds, both TCP-DOPA-Tris and TCP-DOPA-SBF scaffolds significantly promoted the osteogenesis of bone marrow stromal cells (BMSCs) as well as the angiogenesis of human umbilical vein endothelial cells (HUVECs), and the TCP-DOPA-SBF group presented the highest in vitro osteogenic/angiogenic activity among the three groups. Furthermore, both TCP-DOPA-Tris and TCP-DOPA-SBF scaffolds significantly improved the formation of new bone in vivo as compared to TCP scaffolds without a nanostructured surface. Our results suggest that the utilization of a mussel-inspired Ca, P-chelated polydopamine nanolayer on 3D plotted bioceramic scaffolds is a viable and effective strategy to construct a hierarchical structure for synergistically accelerating osteogenesis. PMID- 27380636 TI - Impact of Radical Hysterectomy on Survival in Patients with Stage 2 Type1 Endometrial Carcinoma: A Matched Cohort Study. AB - BACKGROUND: In cases of stage 2 endometrial cancers (ECs), a radical hysterectomy is recommended; however, its benefits are poorly documented. OBJECTIVE: The aim of this study was to determine whether a primary radical hysterectomy improves specific and overall survival compared with a simple hysterectomy in stage 2 EC. METHODS: Data from all women with type 1 EC and International Federation of Gynecology and Obstetrics (FIGO) 2009 stage 2 who underwent surgical treatment between January 1998 and December 2012 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Women treated with radical hysterectomy were matched with women treated with simple hysterectomy according to demographic and tumoral criteria. The primary endpoint was cancer-related survival. RESULTS: One-to-two matching enabled a comparison of 273 patients who underwent a radical hysterectomy for stage 2 EC (case group) with 546 patients who received a simple hysterectomy (control group). The probability of cancer related survival was not significantly different in the case group compared with the control group (p = 0.08), and the 3-year cancer-related survivals in the radical and simple hysterectomy groups were 88.7 and 94.1 %, respectively. Following adjustment for radiation, survival analysis indicated there was no survival difference between the two groups with regard to cancer-related survival or overall survival. CONCLUSION: The present study indicates that for patients with stromal cervical invasion and type 1 EC, the type of hysterectomy does not impact cancer-related or overall survival, even after adjustment for adjuvant radiation. This finding suggests that additional, randomized clinical studies are required. PMID- 27380637 TI - Standardizing of Pathology in Patients Receiving Neoadjuvant Chemotherapy. AB - The use of neoadjuvant systemic therapy for the treatment of breast cancer patients is increasing. Pathologic response in the form of pathologic complete response (pCR) and grading systems of partial response, such as the residual cancer burden (RCB) system, gives valuable prognostic information for patients and is used as a primary endpoint in clinical trials. The breast cancer and pathology communities are responding with efforts to standardize pathology in patients receiving neoadjuvant chemotherapy. In this review, we summarize the challenges that postneoadjuvant systemic therapy surgical specimens pose and how pathologists and the multidisciplinary team can work together to optimize handling of these specimens. Multidisciplinary communication is essential. A single, standardized approach to macroscopic and microscopic pathologic examination makes it possible to provide reliable response information. This approach employs a map of tissue sections to correlate clinical, gross, microscopic, and imaging findings in order to report the presence of pCR (ypT0 ypN0 and ypT0/is ypN0) versus residual disease, the ypT and ypN stage using the current AJCC/UICC staging system, and the RCB. PMID- 27380635 TI - The relationship between lower limb proprioceptive sense and locomotor skill acquisition. AB - Sensorimotor integration is essential for controlling movement and acquiring new motor tasks in humans. The aim of this project was to understand how lower limb proprioceptive sense contributes to the acquisition of a skilled walking task. We assessed lower limb joint position and movement detection sense in healthy human subjects using the Lokomat robotic exoskeleton. Subjects walked on a treadmill to practice a skilled motor task (200 trials) requiring them to match their foot height during the swing phase to the height of a virtual obstacle displayed on a monitor in front of them. Subjects were given visual feedback on their error relative to the obstacle height after it was crossed. Lower limb joint position sense was related to the final performance error, but not the learning rate of the skilled walking task. The findings from this study support the role of lower limb proprioceptive sense on locomotor skill performance in healthy adult subjects. PMID- 27380638 TI - Expression of PD-L1 and HLA Class I in Esophageal Squamous Cell Carcinoma: Prognostic Factors for Patient Outcome. AB - BACKGROUND: Programmed cell death 1 ligand 1 (PD-L1) and human leukocyte antigen (HLA) class I molecules on malignant cell surfaces are pivotal for tumor immunity. The clinical significance of their expression in patients with esophageal squamous cell carcinoma (ESCC) remains to be determined. METHODS: PD L1 and HLA class I protein expression was investigated by immunohistochemical staining of resected specimens from 90 ESCC patients who underwent radical surgery without preoperative therapy. The relationships between the expression of PD-L1 and HLA class I and clinicopathologic factors and patient prognosis were assessed. RESULTS: High expression of PD-L1 and HLA class I were observed in 17 (18.9 %) and 35 (38.9 %) of 90 cases, respectively. High PD-L1 expression was correlated with the depth of tumor invasion (P = 0.0379), lymph node metastasis (P = 0.0031), recurrence (P = 0.0085), and poor overall survival (OS) (5-year survival rate; low/high: 60.9/28.4 %, P = 0.0110). Among those patients with high expression of HLA class I, high PD-L1 expression was correlated with significantly poorer recurrence-free survival (median survival time, low/high: 102.5/3.1 months, P = 0.0016) and poorer OS (median survival time, low/high: 102.5/13.1 months, P = 0.0027). Multivariate analysis showed that combined high PD-L1/high HLA class I expression was an independent prognostic factor for recurrence-free survival (hazard ratio 2.88, 95 % confidence interval 1.02-7.04, P = 0.0455) and OS (hazard ratio 2.95, 95 % confidence interval 1.03-7.50, P = 0.0447). CONCLUSIONS: High PD-L1 expression was a significant independent prognostic factor in ESCC patients with high HLA class I expression. PMID- 27380639 TI - Effect of Neoadjuvant Radiation Dose and Schedule on Nodal Count and Its Prognostic Impact in Stage II-III Rectal Cancer. AB - BACKGROUND: It is unknown how neoadjuvant treatment schedule affects lymph node count (LNC) and lymph node ratio (LNR) and how these correlate with overall survival (OS) in rectal cancer (RC). METHODS: Data were used from the Belgian PROCARE rectal cancer registry on RC patients treated with surgery alone, short term radiotherapy with immediate surgery (SRT), or chemoradiation with deferred surgery (CRT). The effect of neoadjuvant therapy on LNC was examined using Poisson log-linear analysis. The association of LNC and LNR with overall survival (OS) was studied using Cox proportional hazards models. RESULTS: Data from 4037 patients were available. Compared with surgery alone, LNC was reduced by 12.3 % after SRT and by 31.3 % after CRT (p < 0.001). In patients with surgery alone, the probability of finding node-positive disease increased with LNC, while after SRT and CRT no increase was noted for more than 12 and 18 examined nodes, respectively. Per node examined, we found a decrease in hazard of death of 2.7 % after surgery alone and 1.5 % after SRT, but no effect after CRT. In stage III patients, the LNR but not (y)pN stage was significantly correlated with OS regardless of neoadjuvant therapy. Specifically, a LNR > 0.4 was associated with a significantly worse outcome. CONCLUSIONS: Nodal counts are reduced in a schedule-dependent manner by neoadjuvant treatment in RC. After chemoradiation, the LNC does not confer any prognostic information. A LNR of >0.4 is associated with a significantly worse outcome in stage III disease, regardless of neoadjuvant therapy type. PMID- 27380640 TI - Risk Stratification in Patients with Stage II Colon Cancer. AB - BACKGROUND: The decision to receive adjuvant chemotherapy is far from evident and remains controversial in patients with American Joint Committee on Cancer stage II colon cancer. This study analyzes several pathological characteristics in order to assess their (combined) predictive value for outcomes in stage II colon cancer. METHODS: All stage II patients treated surgically for colon cancer at our tertiary care center (2004-2011) were extracted from a prospectively maintained, Institutional Review Board-approved data repository (n = 313). Mortality and metastasis were compared, including multivariable Cox regression adjusted for stage subdivisions (IIA/IIB/IIC) and potential confounders. RESULTS: Colon cancer specific mortality was substage independently increased in patients with baseline carcinoembryonic antigen (CEA) >5 ng/L [hazard ratio (HR) 2.88; p = 0.022], large vessel invasion (LVI; HR 4.59; p < 0.001), perineural invasion (HR 3.08; p = 0.006), and extramural vascular invasion (EMVI; HR 4.96; p < 0.001). Overall mortality adjusted for substage, age, and comorbidity was also significantly higher in patients with high-grade disease (HR 2.54; p < 0.001), LVI (HR 1.74; p = 0.015), perineural (HR 2.42; p < 0.001), and EMVI (HR 2.79; p < 0.001). Metastatic recurrence adjusted for adjuvant chemotherapy status had substage independent associations with baseline CEA >5 ng/L (HR 2.37; p = 0.046), LVI (HR 3.07; p = 0.001), perineural invasion (HR 2.57; p = 0.010), and EMVI (HR 2.83; p = 0.002). The number of high-risk features (0, 1, 2-3, 4+) was associated with a clear incremental increase in overall and disease-specific mortality and recurrence (p <= 0.001). The major inflection point is at two high-risk characteristics or more, whereas 5-year survival is almost halved from 77.4 % to 31.7 % (p < 0.001). CONCLUSIONS: The risk score introduced provides a prognostic tool based on readily available data extracted from baseline pathology and preoperative CEA, which provides an easy method to stratify risks of mortality and recurrence and may therefore help in treatment decisions after surgery in stage II patients. PMID- 27380641 TI - Significant Role of Palliative Gastrectomy in Selective Gastric Cancer Patients with Peritoneal Dissemination: A Propensity Score Matching Analysis. AB - OBJECTIVE: The aim of this study was to explore whether palliative gastrectomy is suitable for gastric cancer patients with peritoneal metastasis, and for patients in whom the type of peritoneal metastasis should be selected to receive palliative gastrectomy. METHODS: A total of 747 patients diagnosed with gastric adenocarcinoma with peritoneal metastasis at our centers between January 2000 and April 2014 were retrospectively analyzed. After propensity score matching, the clinicopathologic characteristics and clinical outcomes of patients with peritoneal dissemination were analyzed. RESULTS: After propensity score matching, the median overall survival (OS) of patients in the gastrectomy group was longer than that for patients in the non-gastrectomy group (11.87 vs. 9.27 months; p = 0.020). Patients who received first-line chemotherapy had a significantly longer median OS than those who did not (11.97 vs. 7.03 months; p < 0.001); among these patients, those undergoing more than eight periods of first-line chemotherapy benefited the most (p < 0.001). Subgroup analyses revealed that patients classified as P1 who were undergoing chemotherapy benefited from gastrectomy (p = 0.024), and patients without multisite metastasis also benefited from gastrectomy with regard to OS (p = 0.007). In the multivariate survival analysis, multisite distant metastasis was the independent poor prognostic factor (p < 0.001), while palliative gastrectomy (p = 0.006) and a period of first-line chemotherapy (p < 0.001) were good prognostic factors. Morbidity rates in the gastrectomy and non gastrectomy groups were 10.4 and 1.0 %, respectively (p = 0.003); however, no difference in mortality was noted between the two groups (p = 0.590). CONCLUSIONS: Palliative gastrectomy can prolong the survival of P1 patients without multisite distant metastasis when combined with more than five periods, and particularly more than eight periods, of first-line chemotherapy. PMID- 27380642 TI - Clinical Prognostic Markers in Stage IIIB Melanoma. AB - BACKGROUND: Locoregional treatment is often insufficient to guarantee long-term disease-free survival (DFS) in American Joint Committee on Cancer stage IIIB melanoma, and, in order to improve survival, effective neoadjuvant and adjuvant strategies are needed . Selecting patients for these strategies requires risk stratification, for which clinical and molecular biomarkers can be used. We aimed to detect clinical biomarkers to identify high-risk stage IIIB melanoma patients. PATIENTS AND METHODS: We performed retrospective analysis of stage IIIB melanoma patients who underwent lymph node dissection (LND) in our institution between 2000 and 2015. Sentinel node-positive patients with ulcerated primary tumors, as well as patients with clinically detectable nodal metastasis with non-ulcerated tumors, were included. Baseline characteristics, melanoma-specific survival (MSS), and DFS were assessed, and prognostic factors for recurrence and survival were analyzed, using univariate and multivariate analysis. RESULTS: Overall, 250 patients were included. Median follow-up was 52 months (interquartile range 29 108 months), median MSS was 141 months, and median DFS was 36 months. Five- and 10-year MSS was 59 and 52 %, respectively, and 5- and 10-year DFS was 47 and 41 %, respectively. Age >50 years, Breslow thickness >2 versus <=2 mm, and N2 versus N1 disease all carried an increased risk of death by melanoma. Age >50 years and extracapsular extension carried an increased risk of disease recurrence after LND. CONCLUSIONS: Age >50 years, Breslow thickness >2 mm and N2 versus N1 disease are prognostic factors for poor survival in stage IIIB melanoma. These characteristics can be used to further stratify risk of death by melanoma in this already high-risk patient population and to help select the appropriate population for adjuvant therapy (trials). PMID- 27380643 TI - Oncologic Outcomes After Nipple-Sparing Mastectomy. AB - BACKGROUND: Nipple-sparing mastectomy (NSM) is increasingly used as an alternative to traditional mastectomy because it provides improved aesthetic results. The data on its oncologic safety are limited. The authors' institution has performed NSM during the past 10 years for both oncologic and prophylactic indications. This study aimed to examine oncologic outcomes after NSM for breast cancer. METHODS: The study retrospectively examined all NSM cases managed between July 2007 and July 2013. Descriptive statistics were used to characterize the study cohort. Kaplan-Meier survival analysis was performed to estimate recurrence free survival, specifically the 36-month recurrence-free survival proportion. RESULTS: A total of 721 nipple-sparing mastectomies were performed for 413 patients: 45 (10.9 %) to reduce risk and 368 (89.1 %) for breast cancer. In the breast cancer group, 29.8 % of the patients had ductal carcinoma in situ, and 70.2 % had invasive cancer. The mean follow-up time was 32 months (range 0.01 90.2 months). In the breast cancer group, the Kaplan-Meier 3-year recurrence-free survival rate was 93.6 % (95 % confidence interval, 89.9-96.0 %). Eight patients (2.2 %) had locoregional recurrences, including one in the nipple. Nine patients (2.4 %) had distant recurrence, and six patients (1.6 %) had a diagnosis of both local and distant recurrences. CONCLUSIONS: The findings showed a locoregional recurrence rate of 2.2 %, with an overall recurrence rate of 6.3 % for patients undergoing NSM for the treatment of breast cancer. The majority of these recurrences were distant, with one recurrence at the nipple. These results are promising, but a longer follow-up evaluation of this cohort is necessary. PMID- 27380644 TI - PSF1 (Partner of SLD Five 1) is a Prognostic Biomarker in Patients with Non-small Cell Lung Cancer Treated with Surgery Following Preoperative Chemotherapy or Chemoradiotherapy. AB - BACKGROUND: PSF1 (Partner of SLD Five 1) is an evolutionarily conserved DNA replication factor that is part of the GINS (Go, Ichi, Nii, and San) complex . The objective of this study was to evaluate the relationship between PSF1 expression and prognosis in patients with non-small cell lung cancer (NSCLC) treated with surgery following preoperative chemotherapy or chemoradiotherapy. METHODS: Sixty-nine patients with NSCLC treated with surgery following preoperative chemotherapy or chemoradiotherapy who did not achieve pathologic complete response were enrolled. The status of PSF1 expression was evaluated by immunohistochemistry, and the relationship between expression of PSF1 and Ki-67 was determined, as well as correlations between PSF1 expression and prognosis. RESULTS: We found that 27 of 69 patients' tumors (39 %) were positive for PSF1 expression. The Ki-67 index was significantly higher in the PSF1-positive versus the PSF1-negative group (p = 0.0026). Five-year, disease-free survival of the PSF1-positive group was significantly worse (17.7 vs. 44.3 %, p = 0.0088), and the 5-year overall survival also was worse (16.6 vs. 47.2 %, p = 0.0059). Moreover, PSF1 expression was found to be a significant independent prognostic factor for shorter survival by Cox multivariate analysis (hazard ratio 2.43, 95 % confidence interval 1.27-4.60, p = 0.0076). CONCLUSIONS: PSF1 is a useful prognostic biomarker to stratify NSCLC patients treated with surgery following preoperative chemotherapy or chemoradiotherapy. PMID- 27380645 TI - Advanced Pseudomyxoma Peritonei Requiring Gastrectomy to Achieve Complete Cytoreduction Results in Good Long-Term Oncologic Outcomes. AB - BACKGROUND: Optimal outcomes in pseudomyxoma peritonei (PMP) require complete macroscopic tumor removal by cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Partial or complete gastrectomy may be required with ongoing debate as to the risks and benefits of gastrectomy in what is often a low-grade malignancy. METHODS: Retrospective single-center analysis of 1014 patients undergoing CRS and HIPEC for PMP of appendiceal origin. Complications and survival were compared in patients who had gastrectomy versus the nongastrectomy cohort. RESULTS: Of 1014 patients, 747 (74 %) had CRS and HIPEC with complete cytoreduction. Overall, 86 (12 %) of 747 had partial (n = 80) or total (n = 6) gastrectomy. Median age was 55 years for gastrectomy patients and 56 for nongastrectomy patients (p = 0.591). Preoperative tumor markers [carcinoembryonic antigen, carbohydrate antigen (CA) 125 and CA19 9] were elevated more frequently in the gastrectomy group compared to the nongastrectomy group [81, 61 and 81 % compared to 41 % (p = 0.001), 20 % (p = 0.001) and 39 % (p = 0.001), respectively]. The proportion of high-grade histology was similar in the two groups (gastrectomy 19 % vs. nongastrectomy 18 %, p = 0.882). Postoperative complications (Clavien-Dindo III-IV) were 31 % for the gastrectomy group and 13 % for the nongastrectomy group (p = 0.001). The 30 day postoperative mortality was 3 (0.5 %) of 661 for the nongastrectomy group and 1 (1.2 %) of 86 for the gastrectomy group (p = 0.387). Three- and 5-year overall survival were 96 and 88 % in the nongastrectomy group and 87 and 77 % in the gastrectomy group (p = 0.018). Three- and 5-year disease-free survival were 89 and 77 % in the nongastrectomy group versus 66 and 48 % in the gastrectomy group (p = 0.001). CONCLUSIONS: Gastrectomy is an essential component of complete cytoreduction in advanced PMP and was required in 12 % of patients with good long term survival. PMID- 27380646 TI - Impact of Sarcopenic Obesity on Surgical Site Infection after Laparoscopic Total Gastrectomy. AB - BACKGROUND: The critical risk factors for surgical site infection (SSI) after laparoscopic total gastrectomy (LTG) remain unclear. We analyzed the association between body composition and SSI after LTG. METHODS: We performed a retrospective study of patients with gastric cancer who underwent LTG between March 2006 and October 2014 at Kyoto University Hospital, Japan. Visceral fat area and skeletal muscle mass were assessed from preoperative computed tomography scans to define sarcopenia and obesity. Patients were classified into one of four body composition categories according to the presence or absence of sarcopenia or obesity. The incidence of SSI was compared between the four body composition categories. RESULTS: Of the 157 eligible patients, 45 (24 %) fulfilled the criteria for sarcopenic obesity, 28 (18 %) for nonsarcopenic obesity, 52 (33 %) for sarcopenic nonobesity, and 32 (20 %) for nonsarcopenic nonobesity. Thirty-two patients developed SSI (overall incidence rate, 20 %). The incidence of SSI in each body composition category was 33, 25, 13, and 9 %, respectively (P = 0.03). Multivariate logistic regression analysis showed that only sarcopenic obesity was associated with an increased incidence of SSI (odds ratio 4.59, 95 % confidence interval 1.18-17.78, P = 0.028). CONCLUSIONS: Sarcopenic obesity is an independent risk factor for the development of SSI after LTG. PMID- 27380647 TI - Evaluating the effectiveness of a patient storytelling DVD intervention to encourage physician-patient communication about nonsteroidal anti-inflammatory drug (NSAID) use. AB - OBJECTIVE: To evaluate the effectiveness of a culturally-sensitive, patient storytelling intervention to enhance physician-patient communication about NSAID risk. METHODS: A group randomized trial of 40 medical practices in Alabama was conducted. Patients within intervention practices received a 13-minute DVD that included patient stories related to their experiences with NSAIDs, adverse effects, and importance of communication with their physicians. The proportion of patients who: (1) spoke with their physician about NSAID risk; and (2) used both prescription and over-the-counter (OTC) NSAIDS were primary outcomes. Generalized estimating equations for panel data were used for analysis. RESULTS: Intention-to treat analyses revealed no significant differences between intervention (n=102) and control (n=106) groups for patients speaking with their physician about NSAID risk or concomitant use of prescription/OTC NSAIDs (Odds Ratio [OR]=1.11, p=0.670; OR=0.87, p=0.632, respectively). For 54% of patients who watched the DVD, per-protocol (PP) analyses trended toward increased odds of patients speaking with their physician about prescription NSAID risk compared to the control group [OR=1.37, p=0.354] and lower odds of concomitant prescription/OTC NSAIDs use [OR=0.79, p=0.486]. CONCLUSIONS: A patient storytelling intervention in DVD format alone may not increase patient-physician interaction. PRACTICE IMPLICATIONS: Strategies that facilitate use of patient educational materials delivered by DVD are needed. PMID- 27380649 TI - Implementing a Hospitalist Program in a Critical Access Hospital. AB - PURPOSE: The hospitalist model of inpatient care has rapidly expanded, but little is known about hospitalist care in critical access hospitals (CAHs). We aimed to determine the impact of a hospitalist model of care on staff satisfaction, patient volumes, patient satisfaction, length of stay, and care quality in a CAH. METHODS: We initiated a hybrid rotating hospitalist program in September 2008 at Winneshiek Medical Center (Decorah, Iowa), a 25-bed rural CAH. We reviewed patient volumes, Centers for Medicare and Medicaid Services core quality measures, acute length of stay, and staff satisfaction for primary care hospitalist physicians and inpatient and clinic nurses. Patient volume and length of stay were compared with CAH data reported by the Iowa Hospital Association. FINDINGS: Patient volumes (acute, skilled, and observation) increased by 15% compared with a 17% decrease for statewide CAHs. Length of stay decreased from 2.88 to 2.75 days and remained lower than the average stay for Iowa CAHs (3.05 days). In the year after implementation, we observed no deterioration in core quality measures (range, 93%-100%) or patient satisfaction (86th percentile). Inpatient nurse satisfaction and primary care-hospitalist satisfaction improved. Early clinic nurse skepticism showed improved satisfaction at the 5-year review. CONCLUSIONS: Hospitalist care contributed to ongoing delivery of high-quality care and satisfactory patient experiences while supporting the mission of a CAH in rural Iowa. Implementation required careful consideration of its effects on the outpatient practice. Broader implementation of this model in CAHs may be warranted. PMID- 27380648 TI - Patterns of theta oscillation reflect the neural basis of individual differences in epistemic motivation. AB - Theta oscillations in the EEG have been shown to reflect ongoing cognitive processes related to mental effort. Here, we show that the pattern of theta oscillation in response to varying cognitive demands reflects stable individual differences in the personality trait epistemic motivation: Individuals with high levels of epistemic motivation recruit relatively more cognitive resources in response to situations possessing high, compared to low, cognitive demand; individuals with low levels do not show such a specific response. Our results provide direct evidence for the theory of the construct need for cognition and add to our understanding of the neural processes underlying theta oscillations. More generally, we provide an explanation how individual differences in personality traits might be represented on a neural level. PMID- 27380650 TI - Long-term exposure to fine particulate matter air pollution and the risk of lung cancer among participants of the Canadian National Breast Screening Study. AB - Recently, air pollution has been classified as a carcinogen largely on the evidence of epidemiological studies of lung cancer. However, there have been few prospective studies that have evaluated associations between fine particulate matter (PM2.5 ) and cancer at lower concentrations. We conducted a prospective analysis of 89,234 women enrolled in the Canadian National Breast Screening Study between 1980 and 1985, and for whom residential measures of PM2.5 could be assigned. The cohort was linked to the Canadian Cancer Registry to identify incident lung cancers through 2004. Surface PM2.5 concentrations were estimated using satellite data. Cox proportional hazards models were used to characterize associations between PM2.5 and lung cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) computed from these models were adjusted for several individual-level characteristics, including smoking. The cohort was composed predominantly of Canadian-born (82%), married (80%) women with a median PM2.5 exposure of 9.1 ug/m(3) . In total, 932 participants developed lung cancer. In fully adjusted models, a 10 ug/m(3) increase in PM2.5 was associated with an elevated risk of lung cancer (HR: 1.34; 95% CI = 1.10, 1.65). The strongest associations were observed with small cell carcinoma (HR: 1.53; 95% CI = 0.93, 2.53) and adenocarcinoma (HR: 1.44; 95% CI = 1.06, 1.97). Stratified analyses suggested increased PM2.5 risks were limited to those who smoked cigarettes. Our findings are consistent with previous epidemiological investigations of long-term exposure to PM2.5 and lung cancer. Importantly, they suggest associations persist at lower concentrations such as those currently found in Canadian cities. PMID- 27380651 TI - Steroid 21-hydroxylase deficiency in congenital adrenal hyperplasia. AB - Congenital adrenal hyperplasia (CAH) refers to a group of inherited genetic disorders involving deficiencies in enzymes that convert cholesterol to cortisol within the adrenal cortex. There are five key enzymes involved in the production of cortisol. Of these key enzymes, deficiency of 21-hydroxylase is the most commonly defective enzyme leading to CAH representing more than 90% of cases. The low adrenal cortisol levels associated with CAH affects the hypothalamic pituitary-adrenal negative feedback system leading to increased pituitary adrenocorticotropic hormone (ACTH) production, which overstimulates the adrenal cortex in an attempt to increase cortisol production resulting in a hyperplastic adrenal cortex. The deficiency of enzyme 21-hydroxylase results from mutations or deletions in the CYP21A2 gene found on chromosome 6p. The disorder is transmitted as an autosomal recessive pattern and specific mutations may be correlated to enzymatic compromise of varying degrees, leading to the clinical manifestation of 21-hydroxylase deficiency (21-OHD) CAH. PMID- 27380652 TI - Feline panleukopaenia virus in captive non-domestic felids in South Africa. AB - An outbreak of feline panleukopaenia virus (FPLV) infection was diagnosed by pathology, electron microscopy and polymerase chain reaction (PCR) in vaccinated captive-bred subadult cheetahs in South Africa. Subsequent to this disease outbreak, 12 cases of FPLV diagnosed on histology were confirmed by PCR in captive African black-footed cat, caracal, cheetah, lion, ocelot and serval. Phylogenetic analyses of the viral capsid protein gene on PCR-positive samples, vaccine and National Center for Biotechnology Information (NCBI) reference strains identified a previously unknown strain of FPLV, present since at least 2006, that differs from both the inactivated and the modified live vaccine strains. A previously described South African strain from domestic cats and cheetahs was identified in a serval. Surveys of FPLV strains in South African felids are needed to determine the geographical and host species distribution of this virus. Since non-domestic species may be reservoirs of parvoviruses, and since these viruses readily change host specificity, the risks of FPLV transmission between captive-bred and free-ranging carnivores and domestic cats and dogs warrant further research. PMID- 27380654 TI - Comparative performance of traps in catching tsetse flies (Diptera: Glossinidae) in Tanzania. AB - This study was conducted to determine the efficiency of different tsetse traps in 28 sites across Tanzania. The traps used were biconical, H, NGU, NZI, pyramidal, S3, mobile, and sticky panels. Stationary traps were deployed at a distance of 200 m apart and examined 72 h after deployment. The results showed that 117 (52.2%) out of the 224 traps deployed captured at least one Glossina species. A total of five Glossina species were captured, namely Glossina brevipalpis, Glossina pallidipes, Glossina swynnertoni, Glossina morsitans, and Glossina fuscipes martinii. Biconical traps caught tsetse flies in 27 sites, pyramidal in 26, sticky panel in 20, mobile in 19, S3 in 15, NGU in 7, H in 2 and NZI in 1. A total of 21 107 tsetse flies were trapped, with the most abundant species being G. swynnertoni (55.9%), followed by G. pallidipes (31.1%), G. fuscipes martinii (6.9%) and G. morsitans (6.0%). The least caught was G. brevipalpis (0.2%). The highest number of flies were caught by NGU traps (32.5%), followed by sticky panel (16%), mobile (15.4%), pyramidal (13.0%), biconical (11.3%) and S3 (10.2%). NZI traps managed to catch 0.9% of the total flies and H traps 0.7%. From this study, it can be concluded that the most efficient trap was NGU, followed by sticky panel and mobile, in that order. Therefore, for tsetse fly control programmes, NGU traps could be the better choice. Conversely, of the stationary traps, pyramidal and biconical traps captured tsetse flies in the majority of sites, covering all three ecosystems better than any other traps; therefore, they would be suitable for scouting for tsetse infestation in any given area, thus sparing the costs of making traps for each specific Glossina species. PMID- 27380653 TI - An update of the tsetse fly (Diptera: Glossinidae) distribution and African animal trypanosomosis prevalence in north-eastern KwaZulu-Natal, South Africa. AB - An unpredicted outbreak of African animal trypanosomosis or nagana in 1990 in north-eastern KwaZulu-Natal necessitated an emergency control programme, utilising the extensive cattledipping system in the area, as well as a reassessment of the tsetse and trypanosomosis problem in the province. Since 1990, sporadic blood sampling of cattle at the dip tanks in the naganainfested areas were undertaken to identify trypanosome species involved and to determine the infection prevalence in cattle. The distribution and species composition of the tsetse populations in the area were also investigated. From November 2005 to November 2007 selected dip tanks were surveyed for trypanosome infection prevalence. During April 2005 to August 2009 the distribution and abundance of tsetse populations were assessed with odour-baited H traps. The tsetse and trypanosome distribution maps were updated and potential correlations between tsetse apparent densities (ADs) and the prevalence of trypanosomosis were assessed. Glossina brevipalpis Newstead and Glossina austeni Newstead were recorded in locations where they have not previously been collected. No significant correlation between tsetse relative abundance and nagana prevalence was found, which indicated complex interactions between tsetse fly presence and disease prevalence. This was epitomised by data that indicated that despite large differences in the ADs of G. austeni and G. brevipalpis, trypanosome infection prevalence was similar in all three districts in the area. This study clearly indicated that both tsetse species play significant roles in trypanosome transmission and that it will be essential that any control strategy, which aims at sustainable management of the disease, should target both species. PMID- 27380655 TI - A retrospective study of the prevalence of bovine fasciolosis at major abattoirs in Botswana. AB - A retrospective study covering a period of ten years (2001-2010) was conducted using postmortem meat inspection records of the Department of Veterinary Services in Gaborone to determine the prevalence of bovine fasciolosis in Botswana. Meat inspection records of monthly and annual returns from the two main export abattoirs in the country were examined, as well as the data collected on the total number of cattle slaughtered and the number of livers condemned due to Fasciola gigantica infection. Only 1250 of the approximately 1.4 million cattle slaughtered were infected with F. gigantica (0.09%, 95% confidence intervals [CI] 0.0% - 0.3%). No distinct seasonal pattern was observed in condemnation rates of livers. However, the pattern of distribution of fasciolosis was higher (but not significant) in cattle that originated from areas with high rainfall and more permanent water bodies than those from relatively low rainfall areas with a transitory water system. It is recommended that a longitudinal survey should be carried out at the abattoirs and farms to determine the prevalence of the disease in cattle of different ages, sex and breed as well as the place of origin in the country. The present study indicated that the prevalence of fasciolosis in cattle is low and the disease is therefore of less significance in Botswana than other African countries for which information is available. PMID- 27380657 TI - Seacole statue is a triumph for hope over hate. AB - During the RCN congress debate on whether the UK should leave the European Union, prominent college activist Jason Warriner said that nurses would play a vital role in 'healing the nation' after the vote, whatever the outcome. Unfortunately his prophecy has proved to be correct, with the UK being divided in way that few of us have experienced before. PMID- 27380658 TI - Memorial to Mary Seacole unveiled. AB - A bronze statue honouring Crimean War hero and nurse Mary Seacole was unveiled in London last week following a 13-year campaign and L500,000 fundraising appeal. PMID- 27380656 TI - Enhanced expression of recombinant beta toxin of Clostridium perfringens type B using a commercially available Escherichia coli strain. AB - Clostridium perfringens beta toxin is only produced by types B and C and plays an important role in many human and animal diseases, causing fatal conditions that originate in the intestines. We compared the expression of C. perfringens type B vaccine strain recombinant beta toxin gene in the Escherichia coli strains Rosetta(DE3) and BL21(DE3). The beta toxin gene was extracted from pJETbeta and ligated with pET22b(+). pET22beta was transformed into E. coli strains BL21(DE3) and Rosetta(DE3). Recombinant protein was expressed as a soluble protein after isopropyl beta-D-1-thiogalactopyranoside (IPTG) induction in strain Rosetta(DE3) but not in BL21(DE3). Expression was optimised by growing recombinant cells at 37 degrees C and at an induction of 0.5 mM, 1 mM, 1.5 mM IPTG. Expression was evaluated using sodium dodecyl sulfate Polyacrylamide gel electrophoresis (SDS PAGE). The recombinant protein was purified via Ni-NTA and was analysed using western blot. We concluded that E. coli strain RosettaTM(DE3) can enhance the expression of C. perfringens recombinant beta toxin. PMID- 27380660 TI - NMC hearing finds nurses who falsified records did so under orders from bosses. AB - Two senior nurses who falsified emergency department waiting time figures amid a 'climate of intimidation and bullying' have been told by the Nursing and Midwifery Council that they face no further action against them. PMID- 27380659 TI - Brexit vote prompts warning over bursary. AB - Unions have put pressure on the government to suspend proposals to scrap the nursing student bursary in the wake of the Brexit vote. PMID- 27380661 TI - Brexit may not affect recruitment from EU. AB - The Brexit vote is 'unlikely' to have an immediate effect on NHS recruitment of European Union nurses, according to a leading academic. PMID- 27380662 TI - Stepping Hill killer appeals sentence. AB - Nurse Victorino Chua's legal appeal against his conviction for poisoning and murdering hospital patients will take place later this month. PMID- 27380663 TI - College demands better children's cardiac care. AB - The RCN has called for health services across the UK to 'learn the vital lessons' from an independent review of cardiac services at Bristol Royal Hospital for Children. PMID- 27380666 TI - Palliative care still viewed as 'giving up on a patient'. AB - Nurses could play a pivotal role in reducing 'invasive and potentially harmful' treatments experienced by older people during their last weeks of life, a leading cancer nurse has said. PMID- 27380667 TI - NHS 'must ensure' nurses are competent in basic English. AB - Concerns about basic English skills have been raised after the Nursing and Midwifery Council (NMC) made changes to its language tests for overseas nurses. PMID- 27380669 TI - Magic the Labrador trained to sniff out low blood sugar levels. AB - Type 1 diabetes patient Claire Pesterfield's pet Labrador, Magic, really is one of her best friends. PMID- 27380670 TI - Call for unity on safe staffing. AB - Last month, Scotland's first minister Nicola Sturgeon declared Scotland would enshrine safe nurse staffing levels in law. PMID- 27380673 TI - Delayed discharge. AB - Essential facts Delays in discharging older peo ple from hospital cost the NHS L820 million a year, according to a report from the National Audit Office (NAO). Last year in acute hospitals, 1.15 million bed days were lost to delayed transfers of care, an increase of 31% since 2013. The NAO says rising demand for NHS services is compounded by reduced local authority spending on adult social care - down by 10% since 2009-10. PMID- 27380674 TI - ADHD drug use levels off after 18-year boom. AB - Using drugs to treat children with attention deficit hyperactivity disorder (ADHD) may have reached a plateau, after a steep rise in prescriptions over the past 18 years. PMID- 27380675 TI - Eating wholegrain foods may reduce the risk of cancer. AB - A higher intake of wholegrain foods may lower the risk of developing cardiovascular disease and cancer, a new study suggests. A growing body of evidence has emerged on the health benefits of wholegrain foods over the past 10 to 15 years, but recommendations on the daily amount and types have often been unclear or inconsistent. PMID- 27380676 TI - Study sheds light on cancer diagnoses. AB - Younger patients are more likely to be diagnosed with late stage lung cancer than older ones, a new study suggests. PMID- 27380677 TI - Patient information could be misleading. AB - Researchers in Germany have called for more careful reporting of side effects in clinical trials after a study revealed no clear links between medicines that are labelled as sleep disturbing and problems sleeping. PMID- 27380679 TI - 'You're looking well!'. AB - Visiting her mother in hospital some years ago, Jill Fraser noticed something different - she'd had her hair done for the first time since experiencing a major brain haemorrhage. It made all the difference in the world. PMID- 27380680 TI - On the road to positivity. AB - Building an environment where nurses and midwives feel empowered and valued is key to the strategy of many nursing directors, but this can sometimes be a challenge. Signing up to a recognised and evidenced programme can help organisations achieve the progress they are looking for, and is a way of recognising what they have achieved. PMID- 27380681 TI - The vital work of RCN reps. AB - For Gordon Lees, a sense of fairness was at the heart of his decision to become an RCN steward more than 40 years ago. PMID- 27380682 TI - Top tips for reflection. AB - I made a commitment, months ago, to go through revalidation ahead of schedule. It seemed a good idea when sitting by the fire, catching up with emails and Twitter on a dark winter's evening. PMID- 27380683 TI - How to deal with bullying in the workplace. AB - Before you arrange to meet the nurse, ask her to write down precisely what has been happening in as much detail as possible, including the dates, times and locations, as well as the names and job titles of everyone who may have witnessed the bullying. This will help you to determine the seriousness of the incidents. PMID- 27380684 TI - Losing nurse advisers is the final nail in the coffin. AB - Bit by bit, government meddling with the health service is diminishing the nurse's role. PMID- 27380685 TI - Go to the top for rapid action. AB - I started writing to trust chief executives after trying to raise concerns about patient safety with a matron... and getting nowhere. PMID- 27380686 TI - We need abuse training for all. AB - I support mandatory domestic abuse training for all healthcare workers (news, June 22). I attended an emergency department aft er my ex-partner had att acked me. No one asked if I was okay - it was more a case of clean me up, check for injuries and send me on my way. Clearly, the 6Cs were not implemented during my visit. PMID- 27380687 TI - RCN must flex its union muscles. AB - The government wants to condemn nurses to an annual 1% 'pay rise' for the next four years. With inflation this amounts to a 20% pay cut between 2010 and 2020. PMID- 27380689 TI - Don't exclude students. AB - I have just started applying for my first job. I use the website NHS Jobs, but students are oft en excluded by the 'pre-application questions'. These ask if I am registered with the Nursing and Midwifery Council, which I'm not yet. PMID- 27380691 TI - Making time for people at the end. AB - I remember when a patient was admitted to our ward, near the point of death, and there was no one with her - not a soul to see her on her way. PMID- 27380692 TI - Readers' panel - Does the NHS provide a positive working environment? AB - Our experts consider a hot topic of the day. PMID- 27380694 TI - Adult Drug Calculations UK. AB - Developed by Health Education England Thames Valley and Wessex, this app helps users learn how to calculate correct dosages and administer drugs for adults. PMID- 27380696 TI - The first port of call. AB - Nursing students are part of university life, but what they witness during their course can set them apart from their peers. PMID- 27380697 TI - Daunting placement challenged me to change my perspective. AB - With a background in youth work and helping homeless young people, 'nurse' was never a job title in my career plan. But the life choices I had made seemed to lead me to apply to study for a degree in nursing. PMID- 27380698 TI - Vacancy boom encourages nurses back onto the wards. AB - Figures from the Office for National Statistics show a 50% increase in nursing vacancies between 2013 and 2015, so if you're a nurse thinking of going back to practice, now is the time to do it. PMID- 27380699 TI - Feel-good posts outside the NHS offer job satisfaction. AB - Ellen Watters worked as a staff nurse in the NHS before becoming an information specialist nurse for cancer charity Myeloma UK, a post she has held for more than 13 years. PMID- 27380700 TI - 'I enable students in difficulty'. AB - Andrew Pace is a specialist mentor at Diverse Learners ( www.diverse learners.co.uk ), a consultancy providing disability support and training for the healthcare sector. He works with a team of health and social care practitioners and disability specialists. PMID- 27380701 TI - How to record and evidence practice-related feedback for revalidation. AB - Rationale and key points This is the fourth in a series of eight articles providing information about the Nursing and Midwifery Council revalidation process. This article focuses on recording 5 examples of practice-related feedback for revalidation. " Feedback encourages individuals to assess and improve their practice. " Feedback aids communication and interpersonal skills. Reflective activity 'How to' revalidate articles can help to update your practice and provide information about the revalidation process, including how you can record and evidence practice-related feedback for revalidation. Reflect on and write a short account of: 1. How your practice will change as a result of obtaining feedback from patients and colleagues. 2. How you could use this article to educate your colleagues. Subscribers can upload their reflective accounts at: rcni.com/portfolio . PMID- 27380702 TI - Practical guidance on undertaking a service evaluation. AB - This article describes the basic principles of evaluation, focusing on the evaluation of healthcare services. It emphasises the importance of evaluation in the current healthcare environment and the requirement for nurses to understand the essential principles of evaluation. Evaluation is defined in contrast to audit and research, and the main theoretical approaches to evaluation are outlined, providing insights into the different types of evaluation that may be undertaken. The essential features of preparing for an evaluation are considered, and guidance provided on working ethically in the NHS. It is important to involve patients and the public in evaluation activity, offering essential guidance and principles of best practice. The authors discuss the main challenges of undertaking evaluations and offer recommendations to address these, drawing on their experience as evaluators. PMID- 27380703 TI - Gastrointestinal care for older people. AB - This article discusses gastrointestinal (GI) healthcare in older people. It outlines the physiological changes that occur in the GI tract as a result of ageing, and discusses common GI disorders in older people. These GI disorders include dysphagia, gastrointestinal reflux disease, colorectal cancer, diverticular disease, constipation and anaemia. Healthcare professionals should be aware of the factors that may influence gastrointestinal health in older people, including nutrition, hydration and alcohol use, which are important considerations when delivering person-centred care. PMID- 27380704 TI - Developing nursing care plans. AB - What was the nature of the CPD activity and/or practice-related feedback and/or event or experience in your practice? The CPD article discussed the theories involved in developing nursing care plans. Care planning is a fundamental part of nursing, and aims to facilitate standardised, evidence-based and holistic care. PMID- 27380705 TI - Delivering a message of hope. AB - Shelley Perry is a dedicated and passionate mental health practitioner who specialises in supporting people with eating disorders across Lancashire. She is also a social entrepreneur. PMID- 27380706 TI - Hand washing. AB - A surgery matron has writt en a hand hygiene promotional video rap to encourage staff, patients and visitors to wash their hands. Vicky Cartwright from University Hospitals of Leicester NHS Trust rewrote the lyrics to 1990s hit rap, Ice Ice Baby. PMID- 27380707 TI - We must be open and honest. AB - 'We have to put honesty ahead of our fear, because that is the only way to put patients first. Are you ready for this kind of honesty?' PMID- 27380708 TI - Changing approach to psychological trauma. AB - As the Battle of the Somme's anniversary looms and post-traumatic stress disorder continues to be an enduring issue for the armed forces, what lessons in treating mental illness can we learn from the first world war? Claire Chatterton, writing in Mental Health Practice, examines the changes to treating psychological trauma during the Somme by health professionals who had rarely worked with people experiencing mental health problems. PMID- 27380709 TI - New leadership model for learning disability nursing. AB - Could learning disability nurses hold the key to a new direction of care and leadership? Jim Blair, writing in Learning Disability Practice, says there must be a response to the inquiry into premature deaths of people with learning disabilities. One way for a new form of leadership could be band 8 nurses practising at consultant level. With their experiences of caring for people with learning disabilities, nurse consultants can shape service delivery and pathways to enhance quality of care, reduce poor practices and avoidable deaths. PMID- 27380710 TI - Storyboarding used as an aid to explore grief. AB - Yvonne Dexter, writing in Nursing Children and Young People, discusses the use of storyboarding and its use as a reflective practice aid. As children's nurses are among the child health professionals most directly affected by childhood death, storyboarding can provide nursing students with a safe environment to reflect on their feelings about the death of a child. Ms Dexter considers the potential for its use in practice, for example in clinical supervision and classroom settings, to manage grief. PMID- 27380711 TI - Elevated monocyte phosphorylated p38 in nearby employees after a chemical explosion. AB - Personalised health surveillance is infrequent or absent in occupational and environmental medicine. The shortage of functional tests in relevant cells and tissues greatly limits our understanding of environmental exposures and associated disease risk. We evaluated single cell signalling in peripheral blood mononuclear cells from 301 individuals in a cross sectional health survey 18 months after a chemical explosion of sulphorous coker gasoline. The accident created a malodourous environment leading to long-term health complaints. Multiple regression analysis revealed T-cell specific elevated phosphorylation of the stress kinase p-p38 (T180/Y182) among tobacco smokers and monocyte-specific elevated phosphorylation in employees at the explosion site. Other studies of the accident reported reduced tear film stability, and more airway obstruction and subjective health complaints among the employees at the accident site. Elevated monocyte p-p38 in the employee group was independent of such health effects, and could therefore be dependent on the sulphuric malodorous environment. The present study proposes signalling status in leukocytes as a scalable biomarker providing information about environmental exposures. PMID- 27380712 TI - C21 steroidal glycosides from the roots of Cynanchum paniculatum. AB - As a part of our continuing research for bioactive constituents from Cynanchum plants, four new C21 steroidal glycosides, cynapanoside D-G (1-4), together with six known compounds (5-10) were isolated from the roots of Cynanchum paniculatum (Bge.) Kitag. Their structures were elucidated on the basis of 1D- and 2D-NMR spectroscopic data as well as HR-ESI-MS analysis. Compound 8 exhibited potent inhibitory activities against HL-60, HT-29, PC-3 and MCF-7 cell lines with IC50 values of 8.3, 7.5, 34.3 and 19.4MUM, respectively and compounds 1-4 and 9 displayed moderate cytotoxicity against the four cell lines. The in vitro antioxidant activities of compounds 1-4, 8 and 9 were assayed by DPPH radical scavenging activity. Antibacterial and antifungal activities of compounds 1-4, 8 and 9 were also tested. PMID- 27380713 TI - An Integrative Analysis of the Effect of Lifestyle and Pharmacological Interventions on Glucose Metabolism in the Prevention and Treatment of Youth Onset Type 2 Diabetes. AB - Preventing and managing youth-onset type 2 diabetes are a major challenge. This paper reviews the evidence of lifestyle and drug therapies in improving glucose, insulin, and insulin sensitivity. Forty-four interventions were analyzed, of which 11 were drug (mainly metformin) interventions combined with lifestyle while the remainder used lifestyle strategies only. Fewer than a dozen out of 44 interventions reported significant improvements in glucose-related outcomes. Metformin in addition to lifestyle therapy did not necessarily enhance intervention effects. The overall lack of findings can be partially attributed to the heterogeneity of study populations, the lack of intervention intensity, under powered study design, and the challenging lives of at-risk populations. New treatment options in both drugs and lifestyle strategies are direly needed. PMID- 27380714 TI - Annotation of Different Dehydrocatechin Oligomers by MS/MS and Their Occurrence in Black Tea. AB - Dehydrocatechins (DhC's), oligomeric oxidation products of (epi)catechins, were formed in model incubations of epicatechin with mushroom tyrosinase. DhC oligomers up to tetramers were detected by reversed-phase ultrahigh-performance liquid chromatography mass spectrometry (RP-UHPLC-MS) analysis. Measurements with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) showed formation of oligomers up to at least 15 catechin subunits. Isomeric DhC's were obtained, and a method based on MS(2) fragment ratios was set up to distinguish between the different interflavanic configurations of the isomers. In the model incubation, 8 dehydrodicatechins (DhC2's) and 22 dehydrotricatechins (DhC3's) were tentatively annotated by their MS(2) signature fragments. Three different interflavanic configuration types were determined for the DhC2's. DhC2's and DhC3's were shown to occur in a black tea extract for the first time. For the DhC2's, at least two isomeric types, i.e., DhC beta and DhC epsilon, could be annotated in black tea. PMID- 27380715 TI - Embodying Transition in Later Life: "Having a Fall" as an Uncertain Status Passage for Elderly Women in Southeast London. AB - In their (2014 report, the charity AgeUK states that one-third of older people (over 3 million) fall each year. This article takes a focused look at falling by describing four women's accounts of "having a fall" in Walworth, southeast London, which sheds light on the experience of personal and corporeal change in later life. While some experiential studies of falling have made reference to a loss of embodied control and changes in identity, these aspects have not been explored in sufficient depth. Attending closely to the embodied experience of falling for older women in the context of everyday activity reveals the uncertainty surrounding what it actually signifies and the powerful effect this uncertainty has on their everyday lives and sense of self. This in-depth phenomenological account speaks to important gaps in the literature on falls, given the current research emphasis on the management of falls risk. PMID- 27380716 TI - RNAi-combined nano-chemotherapeutics to tackle resistant tumors. AB - The merger of nanotechnology and combination chemotherapy has shown notable promise in the therapy of resistant tumors. The latest scientific attention encompasses the engagement of anticancer drugs in combination with small interfering (si)RNAs, such as VEGF, XLAP, PGP, MRP-1, BCL-2 and cMyc, to name but a few. siRNAs have shown immense promise to knockout drug resistance genes as well as to recover the sensitivity of resistant tumors to anticancer therapy. The nanotechnology approach could also protect siRNA against RNAse degradation as well as prevent off-target effects. In this article, we discuss the approaches that have been used to deliver of siRNA in combination with chemotherapeutic drugs to treat resistant tumors. We also discuss the stipulations that must be considered in formulating a nanotechnology-assisted siRNA-drug cancer therapy. PMID- 27380717 TI - Social support, coping strategies and their correlations with older adults' relocation adjustments after natural disaster. AB - AIM: The present study examines the associations among social support, coping strategies and relocation adjustment outcomes, including community cohesion, residential satisfaction and depressive symptoms, for older persons in Taiwan displaced by Typhoon Morakot. METHODS: This study enrolled 372 adults aged 60 years or older who were relocated to permanent houses after Typhoon Morakot destroyed their homes on 8 August 2009. A path analysis simultaneously examined the hypothesized links among social support, coping strategies and relocation adjustment outcomes. RESULTS: The relationships between coping strategies and relocation outcomes varied. Problem-focused and support-seeking coping were positively related to perceived community cohesion, whereas emotion-focused coping was associated with a high number of depressive symptoms. Social support was positively related to residential satisfaction. Additionally, social support was also indirectly related to increased community cohesion and residential satisfaction through its positive relationship with support-seeking and problem focused coping. CONCLUSIONS: More interventions should be implemented to enhance support within informal networks and a sense of belonging to the new resident community, thereby promoting more active coping strategies, enhancing the effectiveness of coping efforts and maximizing positive adjustment outcomes. Geriatr Gerontol Int 2017; 17: 1006-1014. PMID- 27380719 TI - Noble metal-free bifunctional oxygen evolution and oxygen reduction acidic media electro-catalysts. AB - Identification of low cost, highly active, durable completely noble metal-free electro-catalyst for oxygen reduction reaction (ORR) in proton exchange membrane (PEM) fuel cells, oxygen evolution reaction (OER) in PEM based water electrolysis and metal air batteries remains one of the major unfulfilled scientific and technological challenges of PEM based acid mediated electro-catalysts. In contrast, several non-noble metals based electro-catalysts have been identified for alkaline and neutral medium water electrolysis and fuel cells. Herein we report for the very first time, F doped Cu1.5Mn1.5O4, identified by exploiting theoretical first principles calculations for ORR and OER in PEM based systems. The identified novel noble metal-free electro-catalyst showed similar onset potential (1.43 V for OER and 1 V for ORR vs RHE) to that of IrO2 and Pt/C, respectively. The system also displayed excellent electrochemical activity comparable to IrO2 for OER and Pt/C for ORR, respectively, along with remarkable long term stability for 6000 cycles in acidic media validating theory, while also displaying superior methanol tolerance and yielding recommended power densities in full cell configurations. PMID- 27380720 TI - Solubility and solvation of monosaccharides in ionic liquids. AB - Herein, solubility experimental data for six monosaccharides, viz.d-(+)-glucose, d-(+)-mannose, d-(-)-fructose, d-(+)-galactose, d-(+)-xylose and l-(+)-arabinose, in four ionic liquids (ILs), at temperatures ranging from 288.2 to 348.2 K, were obtained aimed at gathering a better understanding of their solvation ability and molecular-level mechanisms which rule the dissolution process. To ascertain the chemical features that enhance the solubility of monosaccharides, ILs composed of dialkylimidazolium or tetraalkylphosphonium cations combined with the dicyanamide, dimethylphosphate or chloride anions were investigated. It was found that the ranking of the solubility of monosaccharides depends on the IL; yet, d (+)-xylose is always the most soluble while d-(-)-fructose is the least soluble monosaccharide. The results obtained show that both the IL cation and the anion play a major role in the solubility of monosaccharides. Finally, from the determination of the respective thermodynamic properties of solution, it was found that enthalpic contributions are dominant in the solubilization process. However, the observed differences in the solubilities of monosaccharides in 1 butyl-3-methylimidazolium dicyanamide are ruled by a change in the entropy of solution. PMID- 27380721 TI - Genomic analysis of the evolutionary lineage of Norovirus GII.4 from archival specimens during 1975-1987 in Tokyo. AB - This study aimed to analyze NoV GII.4 sequences from archival specimens obtained during 1975-1987 by comparing them with reference sequences. The first NoV GII.P4_GII.4 sequence was identified in 1980. NoV GII.4 collected in 1970 had a GII.P1_GII.4 sequence. These results indicate that the GII.P4_GII.4 sequence may be the result of a recombination that might have occurred around 1980. Amino acid substitutions based on this replacement were mainly accumulated in the NTPase, p22, and RdRp regions. The emergence of GII.P4_GII.4 sequence is considered to have ended the major prevalence of NoV GII.4. J. Med. Virol. 89:363-367, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27380722 TI - The unique peptidome: Taxon-specific tryptic peptides as biomarkers for targeted metaproteomics. AB - The Unique Peptide Finder (http://unipept.ugent.be/peptidefinder) is an interactive web application to quickly hunt for tryptic peptides that are unique to a particular species, genus, or any other taxon. Biodiversity within the target taxon is represented by a set of proteomes selected from a monthly updated list of complete and nonredundant UniProt proteomes, supplemented with proprietary proteomes loaded into persistent local browser storage. The software computes and visualizes pan and core peptidomes as unions and intersections of tryptic peptides occurring in the selected proteomes. In addition, it also computes and displays unique peptidomes as the set of all tryptic peptides that occur in all selected proteomes but not in any UniProt record not assigned to the target taxon. As a result, the unique peptides can serve as robust biomarkers for the target taxon, for example, in targeted metaproteomics studies. Computations are extremely fast since they are underpinned by the Unipept database, the lowest common ancestor algorithm implemented in Unipept and modern web technologies that facilitate in-browser data storage and parallel processing. PMID- 27380723 TI - Cribriform neuroepithelial tumor: molecular characterization of a SMARCB1 deficient non-rhabdoid tumor with favorable long-term outcome. AB - Rhabdoid phenotype and loss of SMARCB1 expression in a brain tumor are characteristic features of atypical teratoid/rhabdoid tumors (ATRT). Rare non rhabdoid brain tumors showing cribriform growth pattern and SMARCB1 loss have been designated cribriform neuroepithelial tumor (CRINET). Small case series suggest that CRINETs may have a relatively favorable prognosis. However, the long term outcome is unclear and it remains uncertain whether CRINET represents a distinct entity or a variant of ATRT. Therefore, 10 CRINETs were clinically and molecularly characterized and compared with 10 ATRTs of each of three recently described molecular subgroups (i.e. ATRT-TYR, ATRT-SHH and ATRT-MYC) using Illumina Infinium HumanMethylation450 arrays, FISH, MLPA, and sequencing. Furthermore, outcome was compared to a larger cohort of 27 children with ATRT TYR. Median age of the 6 boys and 4 girls harboring a CRINET was 20 months. On histopathological examination, all CRINETs demonstrated a cribriform growth pattern and distinct tyrosinase staining. On unsupervised cluster analysis of methylation data, all CRINETs examined exclusively clustered within the ATRT-TYR molecular subgroup. As ATRT-TYR, CRINETs mainly showed large heterozygous 22q deletions (9/10) and SMARCB1 mutations of the other allele. In two patients, SMARCB1 mutations were also present in the germline. Estimated mean overall survival in patients with CRINETs was 125 months (95% confidence interval 100-151 months) as compared to only 53 (33-74) months in patients with ATRTs of the ATRT TYR subgroup (Log-Rank P < 0.05). In conclusion, CRINET represents a SMARCB1 deficient non-rhabdoid tumor, which shares molecular similarities with the ATRT TYR subgroup but has distinct histopathological features and favorable long-term outcome. PMID- 27380724 TI - Destabilizing an interacting motif strengthens the association of a designed ankyrin repeat protein with tubulin. AB - Affinity maturation by random mutagenesis and selection is an established technique to make binding molecules more suitable for applications in biomedical research, diagnostics and therapy. Here we identified an unexpected novel mechanism of affinity increase upon in vitro evolution of a tubulin-specific designed ankyrin repeat protein (DARPin). Structural analysis indicated that in the progenitor DARPin the C-terminal capping repeat (C-cap) undergoes a 25 degrees rotation to avoid a clash with tubulin upon binding. Additionally, the C cap appears to be involved in electrostatic repulsion with tubulin. Biochemical and structural characterizations demonstrated that the evolved mutants achieved a gain in affinity through destabilization of the C-cap, which relieves the need of a DARPin conformational change upon tubulin binding and removes unfavorable interactions in the complex. Therefore, this specific case of an order-to disorder transition led to a 100-fold tighter complex with a subnanomolar equilibrium dissociation constant, remarkably associated with a 30% decrease of the binding surface. PMID- 27380725 TI - Altered expression of long non-coding RNA and mRNA in mouse cortex after traumatic brain injury. AB - BACKGROUND AND OBJECTIVE: The present study aims to detect the altered lncRNA expression in the mouse cortex after traumatic brain injury (TBI). We also simultaneously detected the altered mRNA profile to further analyze the possible function of lncRNA. METHOD: C57BL/6 mice (n=18) were used to construct a controlled cortical impact model. At 24h post-TBI, the cortex around injury site was collected and the total RNA was extracted to construct the cDNA library. RNA sequencing (RNA-seq) was carried out followed by RT-PCR for confirmation. Bioinformatic analysis (including GO analysis, KEGG pathway and co-expression analysis) also were performed. RESULTS: A total of 64,530 transcripts were detected in the current sequencing study, in which 27,457 transcripts were identified as mRNA and 37,073 transcripts as lncRNA. A total of 1580 mRNAs (1430 up-regulated and 150 down-regulated) and 823 lncRNAs (667 up-regulated and 156 down-regulated) were significantly changed according to the criteria ( (|)log2((fold change))|>1 and P<0.05). These altered mRNAs were mainly related to inflammatory and immunological activity, metabolism, neuronal and vascular network. The expression of single lncRNA may be related with several mRNAs, and so was the mRNA. Also, a total of 360 new mRNAs and 8041 new lncRNAs were identified. The good reproducibility and reliability of RNA-seq were confirmed by RT-PCR. CONCLUSION: Numerous lncRNAs and mRNAs were significantly altered in mouse cortex around the injury site 24h after TBI. Our present data may provide a promising approach for further study about TBI. PMID- 27380726 TI - Lack of association between genotype score and sprint/power performance in the Japanese population. AB - OBJECTIVES: This study aimed to examine the association between a total genotype score (TGS) based on previously published genetic polymorphism candidates and differences in sprint/power performance. DESIGN: Case-control association study. METHODS: We analysed 21 polymorphisms, which have previously been associated with sprint/power performance and related phenotypes, in 211 Japanese sprint/power track and field athletes (77 regional, 72 national, and 62 international athletes) and 649 Japanese controls using the TaqMan SNP genotyping assay. We calculated the TGS (maximum value of 100 for the theoretically optimal polygenic score) for the 21 polymorphisms. RESULTS: All groups exhibited similar TGSs (control: 55.9+/-7.2, regional: 55.1+/-7.1, national: 56.1+/-7.4, and international: 56.0+/-7.8, p=0.827 by one-way analysis of variance). Nine of the 21 polymorphisms had the same direction of effect (odds ratio >1.0) as in previous studies, while 12 had the opposite direction of effect (odds ratio <1.0). Three polymorphisms (rs699 in AGT, rs41274853 in CNTFR, and rs7832552 in TRHR), which had the same direction of effect as in previous studies, were associated with international sprint/power athlete status (p<0.05). However, after multiple testing corrections, the statistical significance of these polymorphisms was not retained. CONCLUSIONS: These results suggest that TGSs based on the 21 previously published sprint/power performance-associated polymorphisms did not influence the sprint/power athlete status of Japanese track and field athletes. However, our results maintain the possibility that three of these polymorphisms might be associated with sprint/power performance. PMID- 27380728 TI - Tracing the sources and spatial distribution of organic carbon in subsoils using a multi-biomarker approach. AB - Soil organic carbon (SOC) from aboveground and belowground sources has rarely been differentiated although it may drive SOC turnover and stabilization due to a presumed differing source dependent degradability. It is thus crucial to better identify the location of SOC from different sources for the parameterization of SOC models, especially in the less investigated subsoils. The aim of this study was to spatially assess contributions of organic carbon from aboveground and belowground parts of beech trees to subsoil organic carbon in a Dystric Cambisol. Different sources of SOC were distinguished by solvent-extractable and hydrolysable lipid biomarkers aided by (14)C analyses of soil compartments <63 MUm. We found no effect of the distance to the trees on the investigated parameters. Instead, a vertical zonation of the subsoil was detected. A high contribution of fresh leaf- and root-derived organic carbon to the upper subsoil (leaf- and root-affected zone) indicate that supposedly fast-cycling, leaf derived SOC may still be of considerable importance below the A-horizon. In the deeper subsoil (root-affected zone), roots were an important source of fresh SOC. Simultaneously, strongly increasing apparent (14)C ages (3860 yrs BP) indicate considerable contribution of SOC that may be inherited from the Pleistocene parent material. PMID- 27380727 TI - Cationic lipid-nanoceria hybrids, a novel nonviral vector-mediated gene delivery into mammalian cells: investigation of the cellular uptake mechanism. AB - Gene therapy is a promising technique for the treatment of various diseases. The development of minimally toxic and highly efficient non-viral gene delivery vectors is the most challenging undertaking in the field of gene therapy. Here, we developed dimethyldioctadecylammonium bromide (DODAB)-nanoceria (CeO2) hybrids as a new class of non-viral gene delivery vectors. These DODAB-modified CeO2 nanoparticles (CeO2/DODAB) could effectively compact the pDNA, allowing for highly efficient gene transfection into the selected cell lines. The CeO2/DODAB nanovectors were also found to be non-toxic and did not induce ROS formation as well as any stress responsive and pro-survival signaling pathways. The overall vector performance of CeO2/DODAB nanohybrids was comparable with lipofectamine and DOTAP, and higher than calcium phosphate and DEAE-dextran for transfecting small plasmids. The increased cellular uptake of the nanovector/DNA complexes through clathrin- and caveolae-mediated endocytosis and subsequent release from the endosomes further support the increased gene transfection efficiency of the CeO2/DODAB vectors. Besides, CeO2/DODAB nanovectors could transfect genes in vivo without any sign of toxicity. Taken together, this new nano-vector has the potential to be used for gene delivery in biomedical applications. PMID- 27380730 TI - Nesfatin-1/NUCB2 in the amygdala influences visceral sensitivity via glucocorticoid and mineralocorticoid receptors in male maternal separation rats. AB - BACKGROUND: Nesfatin-1, a recently identified satiety molecule derived from nucleobindin 2 (NUCB2), is associated with visceral hypersensitivity in rats and is expressed in the amygdala. We tested the hypothesis that nesfatin-1 expression in the amygdala is involved in the pathogenesis of irritable bowel syndrome (IBS) visceral hypersensitivity. METHODS: An animal model of IBS-like visceral hypersensitivity was established using maternal separation (MS) during postnatal days 2-16. The role of nesfatin-1 in the amygdala on visceral sensitivity was evaluated. KEY RESULTS: Rats subjected to MS showed a significantly increased mean abdominal withdrawal reflex (AWR) score and electromyographic (EMG) activity at 40, 60, and 80 mmHg colorectal distension. Plasma concentrations of nesfatin-1 and corticosterone were significantly higher than in non-handled (NH) rats. mRNA and protein expression of nesfatin-1/NUCB2 in the amygdala were increased in MS rats, but not in NH rats. In MS rats, AWR scores and EMG activity were significantly decreased after anti-nesfatin-1/NUCB2 injection. In normal rats, mean AWR score, EMG activity, and corticosterone expression were significantly increased after nesfatin-1 injection into the amygdala. Nesfatin-1-induced visceral hypersensitivity was abolished following application of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) antagonists. CONCLUSIONS & INFERENCES: Elevated expression of nesfatin-1/NUCB2 in the amygdala in MS rats suggests a potential role in the pathogenesis of visceral hypersensitivity, which could potentially take place via activation of GR and MR signaling pathways. PMID- 27380729 TI - Comparison of intraoperative anthropometric measurements of the proximal tibia and tibial component in total knee arthroplasty. AB - BACKGROUND: Precise matching of the tibial component and resected bony surfaces and proper rotational implanting of the tibial component are crucial for successful total knee arthroplasty. We aimed to analyze the exact anthropometric proximal tibial data of Japanese patients undergoing total knee arthroplasty and correlate the measurements with the dimensions of current total knee arthroplasty systems. METHODS: A total of 703 knees in 566 Japanese patients who underwent total knee arthroplasty for osteoarthritis were included. The bone resection in the proximal tibia was performed perpendicular to the tibial axis in the frontal plane. Measurements of the proximal tibia were intraoperatively obtained after proximal tibial preparation. RESULTS: There were significant positive correlations between the lateral anteroposterior and medial anteroposterior and mediolateral dimensions. A progressive decrease in the mediolateral/lateral anteroposterior ratio with an increasing lateral anteroposterior dimension or the mediolateral/anteroposterior ratio with an increasing anteroposterior dimension was observed. The lateral anteroposterior dimension was smaller than the medial anteroposterior dimension by a mean of 4.8 +/- 2.0 mm. The proximal tibia exhibited asymmetry between the lateral and medial plateaus. A comparison of the morphological data and dimensions of the implants, one of which was a symmetric tibial component (NexGen) and the others were asymmetric (Genesis II and Persona), indicated that an asymmetric tibial component could be beneficial to maximize tibial plateau coverage. CONCLUSIONS: This study provided important reference data for designing a proper tibial component for Japanese people. The proximal tibial cut surface was asymmetric. There was wide dispersion in the lateral anteroposterior, medial anteroposterior, and mediolateral dimensions depending on the patient. Our data showed that the tibial components of the Genesis II and Persona rather than that of the NexGen may be preferable for Japanese people because of their asymmetric design. PMID- 27380731 TI - Intestinal methane production is associated with decreased weight loss following bariatric surgery. AB - To determine whether methane and hydrogen on breath test affects weight loss after bariatric surgery, 156 subjects (pre-surgery BMI >=33) were recruited >=4 months after surgery. Pre- and post-surgery weights and BMIs were recorded. Post surgery methane and hydrogen levels were determined. % total weight loss and % change in BMI were prorated to six months after surgery. M+/H+ subjects (N=13) exhibited lower prorated % change in BMI vs. all other subjects (N=144) (p=0.13), and significantly lower prorated % total weight loss (p=0.036). These findings may suggest that subjects with positive breath methane and hydrogen lose less weight following bariatric surgery. PMID- 27380732 TI - Student perspectives on using egocentric video recorded by smart glasses to assess communicative and clinical skills with standardised patients. AB - INTRODUCTION: This exploratory study evaluated student perceptions of their ability to self- and peer assess (i) interpersonal communication skills and (ii) clinical procedures (a head and neck examination) during standardised patient (SP) interactions recorded by Google Glass compared to a static camera. METHODS: Students compared the Google Glass and static camera recordings using an instrument consisting of 20 Likert-type items and four open- and closed-text items. The Likert-type items asked students to rate how effectively they could assess specific aspects of interpersonal communication and a head and neck examination in these two different types of recordings. The interpersonal communication items included verbal, paraverbal and non-verbal subscales. The open- and closed-text items asked students to report on more globally the differences between the two types of recordings. Descriptive and inferential statistical analyses were conducted for all survey items. An inductive thematic analysis was conducted to determine qualitative emergent themes from the open text questions. RESULTS: Students found the Glass videos more effective for assessing verbal (t22 = 2.091, P = 0.048) and paraverbal communication skills (t22 = 3.304, P = 0.003), whilst they reported that the static camera video was more effective for assessing non-verbal communication skills (t22 = -2.132, P = 0.044). Four principle themes emerged from the students' open-text responses comparing Glass to static camera recordings for self- and peer assessment: (1) first-person perspective, (2) assessment of non-verbal communication, (3) audiovisual experience and (4) student operation of Glass. DISCUSSION AND CONCLUSION: Our findings suggest that students perceive that Google Glass is a valuable tool for facilitating self- and peer assessment of SP examinations because of students' perceived ability to emphasise and illustrate communicative and clinical activities from a first-person perspective. PMID- 27380734 TI - Further evidence of POP1 mutations as the cause of anauxetic dysplasia. AB - Anauxetic dysplasia (AAD, OMIM 607095) is a rare skeletal dysplasia inherited as an autosomal recessive trait, which is caused by mutations in RMRP and allelic to a more common disorder, cartilage hair hypoplasia (CHH). CHH is a multi-system disorder with a variety of extraskeletal changes. Whereas AAD is a bone restricted disorder with a more severe skeletal phenotype: affected individuals are extremely short and complicated by orthopedic morbidity, and the radiological changes include modification of the vertebral bodies and epiphyseal dysplasia of the hip, as well as generalized metaphyseal dysplasia and severe brachydactyly. Recently, genetic heterogeneity for AAD was proposed, because a familial case (two affected sibs) with an AAD-identical phenotype had compound heterozygous mutations in POP1, encoding a molecule functionally related to the gene product of RMRP. We report here a 5-year-old boy with the same phenotype born to a consanguineous couple. We identified a novel homozygous POP1 mutation (c.1744C>T, p.P582S) in the boy and the heterozygosity in the parents. It may be rational to coin the POP1-associated skeletal phenotype AAD type 2. (c) 2016 Wiley Periodicals, Inc. PMID- 27380735 TI - Mesenchymal stromal cell therapy in ischemic heart disease. AB - Although, treatment of ischemic heart disease (IHD) has improved considerably within the last decades, it is still the main cause of death worldwide. Despite maximum treatment, many IHD patients suffer from refractory angina and heart failure, which severely limits their daily lives. Moreover, IHD is very costly for the health care system. Therefore, new treatment options and strategies are being researched intensely. Stem cell therapy to improve myocardial perfusion and stimulate growth of new cardiomyocytes could be a new way to go. Nevertheless, the results from clinical studies have varied considerably, probably due to the use of many different cell lines obtained from different tissues and the different patient populations. The present review will focus on treatment with the mesenchymal stromal cell from bone marrow and adipose tissue in animal and patients with acute and chronic IHD (CIHD). PMID- 27380736 TI - Cluster-like molybdenum phosphide anchored on reduced graphene oxide for efficient hydrogen evolution over a broad pH range. AB - Cluster-like molybdenum phosphide particles were anchored on reduced graphene oxide (MoP/rGO) with high uniformity by using phosphomolybdic acid as a molybdenum precursor based on a robust assembly-immobilization method. Benefiting from the small size, and even distribution of the MoP particles, the MoP/rGO hybrid exhibits superior electrocatalytic activity towards the hydrogen evolution reaction both in acidic and alkaline media. PMID- 27380733 TI - Dynamic Contrast-enhanced MR Imaging in Renal Cell Carcinoma: Reproducibility of Histogram Analysis on Pharmacokinetic Parameters. AB - Pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been increasingly used to evaluate the permeability of tumor vessel. Histogram metrics are a recognized promising method of quantitative MR imaging that has been recently introduced in analysis of DCE MRI pharmacokinetic parameters in oncology due to tumor heterogeneity. In this study, 21 patients with renal cell carcinoma (RCC) underwent paired DCE-MRI studies on a 3.0 T MR system. Extended Tofts model and population-based arterial input function were used to calculate kinetic parameters of RCC tumors. Mean value and histogram metrics (Mode, Skewness and Kurtosis) of each pharmacokinetic parameter were generated automatically using ImageJ software. Intra- and inter observer reproducibility and scan-rescan reproducibility were evaluated using intra-class correlation coefficients (ICCs) and coefficient of variation (CoV). Our results demonstrated that the histogram method (Mode, Skewness and Kurtosis) was not superior to the conventional Mean value method in reproducibility evaluation on DCE-MRI pharmacokinetic parameters (K( trans) &Ve) in renal cell carcinoma, especially for Skewness and Kurtosis which showed lower intra-, inter observer and scan-rescan reproducibility than Mean value. Our findings suggest that additional studies are necessary before wide incorporation of histogram metrics in quantitative analysis of DCE-MRI pharmacokinetic parameters. PMID- 27380737 TI - Unprecedented Abundance of Protein Tyrosine Phosphorylation Modulates Shigella flexneri Virulence. AB - Evidence is accumulating that protein tyrosine phosphorylation plays a crucial role in the ability of important human bacterial pathogens to cause disease. While most works have concentrated on its role in the regulation of a major bacterial virulence factor, the polysaccharide capsule, recent studies have suggested a much broader role for this post-translational modification. This prompted us to investigate protein tyrosine phosphorylation in the human pathogen Shigella flexneri. We first completed a tyrosine phosphoproteome, identifying 905 unique tyrosine phosphorylation sites on at least 573 proteins (approximately 15% of all proteins). This is the most tyrosine-phosphorylated sites and proteins in a single bacterium identified to date, substantially more than the level seen in eukaryotic cells. Most had not previously been identified and included proteins encoded by the virulence plasmid, which is essential for S. flexneri to invade cells and cause disease. In order to investigate the function of these phosphorylation sites in important virulence factors, phosphomimetic and ablative mutations were constructed in the type 3 secretion system ATPase Spa47 and the master virulence regulator VirB. This revealed that tyrosine residues phosphorylated in our study are critical for Spa47 and VirB activity, and tyrosine phosphorylation likely regulates their functional activity and subsequently the virulence of this major human pathogen. This study suggests that tyrosine phosphorylation plays a critical role in regulating a wide variety of virulence factors in the human pathogen S. flexneri and serves as a base for future studies defining its complete role. PMID- 27380738 TI - Progesterone Receptor Signaling Mechanisms. AB - Progesterone receptor (PR) is a master regulator in female reproductive tissues that controls developmental processes and proliferation and differentiation during the reproductive cycle and pregnancy. PR also plays a role in progression of endocrine-dependent breast cancer. As a member of the nuclear receptor family of ligand-dependent transcription factors, the main action of PR is to regulate networks of target gene expression in response to binding its cognate steroid hormone, progesterone. This paper summarizes recent advances in understanding the structure-function properties of the receptor protein and the tissue/cell-type specific PR signaling pathways that contribute to the biological actions of progesterone in the normal breast and in breast cancer. PMID- 27380740 TI - Thermodynamically Favorable Synthesis of 2-Oxazolidinones through Silver Catalyzed Reaction of Propargylic Alcohols, CO2, and 2-Aminoethanols. AB - Development of catalytic routes to incorporate CO2 into carbonyl compounds at mild conditions remains attractive and challenging. Herein, a one-pot three component cascade reaction of terminal propargylic alcohols, CO2 , and 2 aminoethanols through Ag(I) -based catalysis is reported for the synthesis of carbonyl compounds through C-O/C-N bond formation. This thermodynamically favorable route can be ingeniously regulated to afford a wide range of 2 oxazolidinones along with concurrent production of alpha-hydroxyl ketone derivatives in excellent yields and selectivity. Preliminary mechanistic studies indicate that such a process proceeds through successive formation of alpha alkylidene cyclic carbonate, beta-oxopropylcarbamate, and 2-oxazolidinones. PMID- 27380739 TI - Nurses' experiences with errors in nursing. AB - BACKGROUND: Health care organizations seek to maximize the reporting of medical errors to improve patient safety. PURPOSE: This study explored licensed nurses' decision-making with regard to reporting medical errors. METHODS: Grounded theory methods guided the study. Thirty nurses from adult intensive care units were interviewed, and qualitative analysis was used to develop a theoretical framework based on their narratives. DISCUSSION: The theoretical model was titled "Learning Lessons from the Error." The concept of learning lessons was central to the theoretical model. The model included five stages: Being Off-Kilter, Living the Error, Reporting or Telling About the Error, Living the Aftermath, and Lurking in Your Mind. CONCLUSION: This study illuminates the unique experiences of licensed nurses who have made medical errors. The findings can inform initiatives to improve error reporting and to support nurses who have made errors. PMID- 27380741 TI - Innovation off the beaten path. PMID- 27380742 TI - What is Nano? PMID- 27380743 TI - Environment matters for all. PMID- 27380745 TI - The nanotechnology of life-inspired systems. AB - For some decades now, nanotechnology has been touted as the 'next big thing' with potential impact comparable to the steam, electricity or Internet revolutions - but has it lived up to these expectations? While advances in top-down nanolithography, now reaching 10-nm resolution, have resulted in devices that are rapidly approaching mass production, attempts to produce nanoscale devices using bottom-up approaches have met with only limited success. We have been inundated with nanoparticles of almost any shape, material and composition, but their societal impact has been far from revolutionary, with growing concerns over their toxicity. Despite nebulous hopes that making hierarchical nanomaterials will lead to new, emergent properties, no breakthrough applications seem imminent. In this Perspective, we argue that the time is ripe to look beyond individual nano objects and their static assemblies, and instead focus on systems comprising different types of 'nanoparts' interacting and/or communicating with one another to perform desired functions. Such systems are interesting for a variety of reasons: they can act autonomously without external electrical or optical connections, can be dynamic and reconfigurable, and can act as 'nanomachines' by directing the flow of mass, energy or information . In thinking how this systems nanoscience approach could be implemented to design useful - as opposed to toy model - nanosystems, our choice of applications and our nanoengineering should be inspired by living matter. PMID- 27380746 TI - Don't hesitate, innovate. PMID- 27380747 TI - Spotlights on our sister journals: Chem. Eur. J. 29/2016. PMID- 27380748 TI - Fast and Efficient Oxidative Cycloreversion Reaction of a pi-Extended Photochromic Terarylene. AB - We report herein a dramatic improvement in the kinetics and efficiency of an oxidative cycloreversion reaction of photochromic dithiazolylthiazoles. The cycloreversion reaction of a colored isomer of dithiazolylthiazole proceeds not only by photo-irradiation, but also through chemical oxidation with a net efficiency far exceeding 100 % owing to a chain reaction mechanism. By introducing aromatic groups on the reactive carbon atoms at the ends of a photoreactive 6pi system in a dithiazolylthiazole, the net bleaching reaction rates were increased by up to 1300-fold, and turnover rates increased by two orders of magnitude. Based on a combination of classical kinetic analyses and DFT calculations, we attribute this improvement to acceleration of the rate determining step to produce the active species in the chain-reaction oxidative cycloreversion. PMID- 27380749 TI - Deriving Requirements for Pervasive Well-Being Technology From Work Stress and Intervention Theory: Framework and Case Study. AB - BACKGROUND: Stress in office environments is a big concern, often leading to burn out. New technologies are emerging, such as easily available sensors, contextual reasoning, and electronic coaching (e-coaching) apps. In the Smart Reasoning for Well-being at Home and at Work (SWELL) project, we explore the potential of using such new pervasive technologies to provide support for the self-management of well-being, with a focus on individuals' stress-coping. Ideally, these new pervasive systems should be grounded in existing work stress and intervention theory. However, there is a large diversity of theories and they hardly provide explicit directions for technology design. OBJECTIVE: The aim of this paper is to present a comprehensive and concise framework that can be used to design pervasive technologies that support knowledge workers to decrease stress. METHODS: Based on a literature study we identify concepts relevant to well-being at work and select different work stress models to find causes of work stress that can be addressed. From a technical perspective, we then describe how sensors can be used to infer stress and the context in which it appears, and use intervention theory to further specify interventions that can be provided by means of pervasive technology. RESULTS: The resulting general framework relates several relevant theories: we relate "engagement and burn-out" to "stress", and describe how relevant aspects can be quantified by means of sensors. We also outline underlying causes of work stress and how these can be addressed with interventions, in particular utilizing new technologies integrating behavioral change theory. Based upon this framework we were able to derive requirements for our case study, the pervasive SWELL system, and we implemented two prototypes. Small-scale user studies proved the value of the derived technology-supported interventions. CONCLUSIONS: The presented framework can be used to systematically develop theory-based technology-supported interventions to address work stress. In the area of pervasive systems for well-being, we identified the following six key research challenges and opportunities: (1) performing multi-disciplinary research, (2) interpreting personal sensor data, (3) relating measurable aspects to burn-out, (4) combining strengths of human and technology, (5) privacy, and (6) ethics. PMID- 27380750 TI - Acute anxiety and social inference: An experimental manipulation with 7.5% carbon dioxide inhalation. AB - BACKGROUND: Positive self-bias is thought to be protective for mental health. We previously found that the degree of positive bias when learning self-referential social evaluation decreases with increasing social anxiety. It is unclear whether this reduction is driven by differences in state or trait anxiety, as both are elevated in social anxiety; therefore, we examined the effects on the state of anxiety induced by the 7.5% carbon dioxide (CO2) inhalation model of generalised anxiety disorder (GAD) on social evaluation learning. METHODS: For our study, 48 (24 of female gender) healthy volunteers took two inhalations (medical air and 7.5% CO2, counterbalanced) whilst learning social rules (self-like, self-dislike, other-like and other-dislike) in an instrumental social evaluation learning task. We analysed the outcomes (number of positive responses and errors to criterion) using the random effects Poisson regression. RESULTS: Participants made fewer and more positive responses when breathing 7.5% CO2 in the other-like and other dislike rules, respectively (gas * condition * rule interaction p = 0.03). Individuals made fewer errors learning self-like than self-dislike, and this positive self-bias was unaffected by CO2. Breathing 7.5% CO2 increased errors, but only in the other-referential rules (gas * condition * rule interaction p = 0.003). CONCLUSIONS: Positive self-bias (i.e. fewer errors learning self-like than self-dislike) seemed robust to changes in state anxiety. In contrast, learning other-referential evaluation was impaired as state anxiety increased. This suggested that the previously observed variations in self-bias arise due to trait, rather than state, characteristics. PMID- 27380751 TI - Benzofulvenes in Trienamine Catalysis: Stereoselective Spiroindene Synthesis. AB - The asymmetric formation of spiroindenes containing up to four contiguous stereocenters from the reaction of benzofulvenes with 2,4-dienals through trienamine catalysis is described. The benzofulvene core was found to be an excellent starting point for the synthesis of interesting spiroindenes through a formal cycloaddition pathway. The reaction was mediated by a diphenylprolinol silyl ether catalyst, and a diverse array of spiroindenes were obtained in high yields with excellent stereoselectivity. An attractive feature of the developed system is the possibility to diversify the product scaffold significantly by further manipulation of the chiral spiroindenes. Thus, three intramolecular ring closing reactions following the organocatalytic step resulted in highly complex polycyclic systems. PMID- 27380752 TI - Prevalence of infections among residents of Residential Care Homes for the Elderly in Hong Kong. AB - INTRODUCTION: A point prevalence study was conducted to study the epidemiology of common infections among residents in Residential Care Homes for the Elderly in Hong Kong and their associated factors. METHODS: Residential Care Homes for the Elderly in Hong Kong were selected by stratified single-stage cluster random sampling. All residents aged 65 years or above from the recruited homes were surveyed. Infections were identified using standardised definitions. Demographic and health information-including medical history, immunisation record, antibiotic use, and activities of daily living (as measured by Barthel Index)-was collected by a survey team to determine any associated factors. RESULTS: Data were collected from 3857 residents in 46 Residential Care Homes for the Elderly from February to May 2014. A total of 105 residents had at least one type of infection based on the survey definition. The overall prevalence of all infections was 2.7% (95% confidence interval, 2.2%-3.4%). The three most common infections were of the respiratory tract (1.3%; 95% confidence interval, 0.9%-1.9%), skin and soft tissue (0.7%; 95% confidence interval, 0.5%-1.0%), and urinary tract (0.5%; 95% confidence interval, 0.3%-0.9%). Total dependence in activities of daily living, as indicated by low Barthel Index score of 0 to 20 (odds ratio=3.0; 95% confidence interval, 1.4-6.2), and presence of a wound or stoma (odds ratio=2.7; 95% confidence interval, 1.4-4.9) were significantly associated with presence of infection. CONCLUSIONS: This survey provides information about infections among residents in Residential Care Homes for the Elderly in the territory. Local data enable us to understand the burden of infections and formulate targeted measures for prevention. PMID- 27380753 TI - Clinical applications of high-intensity focused ultrasound. AB - Ultrasound has been developed for therapeutic use in addition to its diagnostic ability. The use of focused ultrasound energy can offer a non-invasive method for tissue ablation, and can therefore be used to treat various solid tumours. High intensity focused ultrasound is being increasingly used in the treatment of both primary and metastatic tumours as these can be precisely located for ablation. It has been shown to be particularly useful in the treatment of uterine fibroids, and various solid tumours including those of the pancreas and liver. High intensity focused ultrasound is a valid treatment option for liver tumours in patients with significant medical co-morbidity who are at high risk for surgery or who have relatively poor liver function that may preclude hepatectomy. It has also been used as a form of bridging therapy while patients awaiting cadaveric donor liver transplantation. In this article, we outline the principles of high intensity focused ultrasound and its clinical applications, including the management protocol development in the treatment of hepatocellular carcinoma in Hong Kong by performing a search on MEDLINE (OVID), EMBASE, and PubMed. The search of these databases ranged from the date of their establishment until December 2015. The search terms used were: high-intensity focused ultrasound, ultrasound, magnetic resonance imaging, liver tumour, hepatocellular carcinoma, pancreas, renal cell carcinoma, prostate cancer, breast cancer, fibroids, bone tumour, atrial fibrillation, glaucoma, Parkinson's disease, essential tremor, and neuropathic pain. PMID- 27380754 TI - Much Ado About Noise. PMID- 27380756 TI - Erratum. PMID- 27380755 TI - Myocardial Infarction Risk Due to Aircraft, Road, and Rail Traffic Noise. AB - BACKGROUND: Traffic noise can induce stress reactions that have effects on the cardiovascular system. The exposure-risk relationship between aircraft, road, and rail traffic noise and myocardial infarction is currently unknown. METHODS: 19 632 patients from the Rhine-Main region of Germany who were diagnosed with myocardial infarction in the years 2006-2010 were compared with 834 734 control subjects. The assignment of persons to groups was performed on the basis of billing and prescription data from three statutory health insurance carriers. The exposure of all insurees to aircraft, road, and rail traffic noise in 2005 was determined from their residence addresses. As estimators of risk, odds ratios (OR) were calculated by logistic regression analysis, with adjustment for age, sex, regional social status variables, and individual social status (if available). The evaluation was performed on the basis of the continuous 24-hour noise level and the categorized noise level (in 5 decibel classes). RESULTS: The linear model revealed a statistically significant risk increase due to road noise (2.8% per 10 dB rise, 95% confidence interval [1.2; 4.5]) and railroad noise (2.3% per 10 dB rise [0.5; 4.2]), but not airplane noise. Airplane noise levels of 60 dB and above were associated with a higher risk of myocardial infarction (OR 1.42 [0.62; 3.25]). This higher risk is statistically significant if the analysis is restricted to patients who had died of myocardial infarction by 2014/2015 (OR 2.70 [1.08; 6.74]. In this subgroup, the risk estimators for all three types of traffic noise were of comparable magnitude (3.2% to 3.9% per 10 dB rise in noise level). CONCLUSION: In this study, a substantial proportion of the population was exposed to traffic noise levels that were associated with an albeit small increase in the risk of myocardial infarction. These findings underscore the importance of effective traffic noise prevention. PMID- 27380758 TI - Embolic Risk Is Time-dependent. PMID- 27380757 TI - The Interdisciplinary Management of Brain Metastases. AB - BACKGROUND: 20-40% of patients with malignant tumors have one or more brain metastases in the course of their illness. Brain metastases are the first manifestation of cancer in 5-10%. Manifestations such as intracranial hypertension or focal neurologic deficits are seen in over 80% of patients with brain metastases. Uncertainty surrounds the treatment of patients with intracranial metastases, as the existing data are derived from trials with low levels of evidence. METHODS: This article is based on a selective literature review and on the authors' own experience of 100 consecutive patients who underwent surgery at the Department of Neurosurgery at Ruhr University Bochum (RUB), Germany. RESULTS: Multimodal treatment enables successful surgery for an increasing number of patients with brain metastases. The modalities and goals of treatment are established for each patient individually by an interdisciplinary tumor board. Drug therapy is usually indicated. Surgical resection followed by stereotactic radiotherapy prolongs mean survival by 3-6 months and lowers the risk of recurrence from 40% to 12.5%. In the authors' own experience, even seriously ill patients can benefit from the resection of brain metastases. The 30 day morbidity was 29%, accounted for mainly by medical complications such as pulmonary embolism, renal failure, and sepsis. CONCLUSION: Through the close interdisciplinary collaboration of neurosurgeons, radiation oncologists, and medical oncologists, the symptomatic state and the prognosis of patients with brain metastases can be improved. Longer overall survival implies that further studies will have to pay special attention to the toxicity of treatment. PMID- 27380759 TI - In Reply. PMID- 27380760 TI - Socioeconomic Disparities and Mortality After a Diagnosis of Dementia: Results From a Nationwide Registry Linkage Study. AB - Low socioeconomic status (SES) has been linked to a higher incidence of dementia. Less is known about the association between SES and mortality in persons with dementia. We studied this association in a prospective cohort of 15,558 patients in the Netherlands between 2000 and 2010. SES was measured using disposable household income and divided in tertiles. Overall, there was a negative relationship between SES and mortality in both sexes and both settings of care. For men who visited a day clinic, the 5-year mortality rate was 74% among those in the lowest tertile of SES and 57% among those in the highest; for women, the rates were 60% and 50%, respectively. The differences in median survival times between persons in the lower and upper tertiles of SES were 260 days for men and 300 days for women. For men who were admitted to the hospital, the 5-year mortality rate was 89% among those in the lowest tertile of SES and 86% among those in the highest; for women, the rates were 83% and 77%, respectively. The differences in median survival times between persons in the lower and upper tertiles of SES were 80 days for men and 130 days for women. Among patients who visited a day clinic, for patients in the lowest tertile of SES versus those in the highest, the adjusted hazard ratio was 1.41 (95% confidence interval: 1.26, 1.57); for those admitted to the hospital, it was 1.14 (95% confidence interval: 1.07, 1.20). In summary, lower SES was associated with a higher mortality risk in both men and women with dementia. The results of the present study should raise awareness in clinicians and caregivers about the unfavorable prognosis in the most deprived patients. PMID- 27380761 TI - Fermented goat milk improves antioxidant status and protects from oxidative damage to biomolecules during anemia recovery. AB - BACKGROUND: Iron deficiency anemia (IDA) is one of the most common nutritional problems in the world, and it is accepted that reactive oxygen species (ROS) production is altered during IDA. The aim of this study was to assess the influence of fermented goat and cow milks on enzymatic antioxidant activities and gene expression, and their role in protecting from oxidative damage during anemia recovery. RESULTS: After feeding the fermented milks-based diets (cow or goat), a significant elevation of some antioxidant endogenous enzymes was found, together with an increase in total antioxidant status (TAS), and a decrease in 8-hydroxy 2'-deoxyguanosine (8-OHdG) was recorded in animals consuming fermented goat milk based diet. In contrast, DNA strand breaks, hydroperoxides, 15-F2t-isoprostanes and protein carbonyl groups were lower in some tissues in animals fed fermented goat milk-based diet, revealing an improvement in both systemic and cellular antioxidant activity of plasma and tissues due to fermented goat milk consumption. CONCLUSION: Fermented goat milk consumption induces a protective increase in TAS together with lower oxidative damage biomarkers, revealing that the milk protects main cell bioconstituents (lipids, protein, DNA, prostaglandins) from evoked oxidative damage during anemia recovery. (c) 2016 Society of Chemical Industry. PMID- 27380763 TI - Lost in translation: evidence to improve outcomes of very preterm infants. PMID- 27380762 TI - Reduction of Minimal Residual Disease in Pediatric B-lineage Acute Lymphoblastic Leukemia by an Fc-optimized CD19 Antibody. AB - Prognosis of primary refractory and relapsed pediatric B-lineage acute lymphoblastic leukemia (ALL) is very poor. Relapse rates significantly correlate with persistent minimal residual disease (MRD). In MRD, favorable effector-target ratios prevail and thus this situation might be optimally suited for immunotherapy with antibodies recruiting immunological effector cells. We here report on the generation, preclinical characterization and first clinical application in B-lineage ALL of an Fc-optimized CD19 antibody. This third generation antibody (4G7SDIE) mediated enhanced antibody-dependent cellular cytotoxicity (ADCC) against leukemic blasts with effector cells from healthy volunteers and B-lineage ALL patients. The antibody was produced in a university owned production unit and was applied on a compassionate use basis to 14 pediatric patients with refractory and relapsed B-lineage ALL at the stage of MRD. In 10/14 patients, MRD was reduced by >= 1 log or below the patient individual detection limit, and 5/14 patients have achieved ongoing complete molecular remission with a median leukemia-free survival of 428 days. Two additional patients died in complete molecular remission due to complications not related to antibody therapy. Besides profound in vivo B-cell depletion, side effects were negligible. A clinical phase 1/2 study to further assess the therapeutic activity of 4G7SDIE is in preparation. PMID- 27380765 TI - Corrigendum. PMID- 27380764 TI - The accuracy and acceptability of performing capillary blood glucose measurements at the earlobe. AB - AIMS: To examine the accuracy and acceptability of capillary blood glucose monitoring using the earlobe. BACKGROUND: In current practice, blood samples for capillary blood glucose monitoring are obtained from the fingertip. Because obtaining blood samples from the fingertip is sometimes contraindicated, it is necessary to identify an alternative site for the procedure. DESIGN: A single patient design with repeated measurements. METHODS: Patients from an outpatient clinic and four medical wards were recruited to the study, in 2014, if they met one of the following criteria: (i) were in a relatively stable glycaemic state; (ii) were currently receiving intravenous infusion; (iii) had been diagnosed with chronic renal impairment or (iv) were aged 65 years or above and bedbound. Blood samples were obtained from the fingertip and the earlobe consecutively for blood glucose monitoring. Participants were asked to rate the respective pain level caused by the procedures. Intra-class correlation coefficient was calculated to demonstrate the level of absolute agreement between the two blood glucose readings. The Wilcoxon signed rank test was used to compare the pain levels. RESULTS: A total of 120 patients participated in the study between February - December 2014. The intra-class correlation coefficient between the readings at the two sampling sites was significantly high, except in a hypoglycaemic state. Participants generally reported a significantly lower level of pain when the earlobe rather than fingertip was pricked. CONCLUSION: The earlobe is to be recommended as a safe alternative site for capillary blood glucose monitoring unless the patient is in a suspected hypoglycaemic state. PMID- 27380767 TI - Morphology of mucosa-associated lymphoid tissue in odontocetes. AB - This study describes the mucosa-associated lymphoid tissue (MALT) in odontocetes from the Brazilian coast and freshwater systems. Seven species were evaluated and tissue samples were analyzed by light, scanning and transmission electron microscopy, and immunohistochemistry. Laryngeal tonsil was a palpable oval mass located in the larynx, composed of a lymphoepithelial complex. Dense collections of lymphocytes were found in the skin of male fetus and calf. Clusters of lymphoid tissue were found in the uterine cervix of a reproductively active juvenile female and along the pulmonary artery of an adult female. Lymphoid tissues associated with the gastrointestinal tract were characterized by diffusely arranged or organized lymphocytes. The anal tonsil was composed of an aggregate of lymphoid tissue occurring exclusively in the anal canal, being composed of squamous epithelium branches. MALT was present in different tissues and organic systems of cetaceans, providing constant protection against mucosal pathogens present in their environment. PMID- 27380768 TI - An investigation of the questions posted on medical consultation websites. AB - BACKGROUND: Online medical consultation has recently become a more and more popular alternative venue for healthcare. It allows patients and caregivers to discuss their health problems and symptoms with qualified medical health professionals via the Internet. OBJECTIVE: This study investigates the questions posted on an asynchronous online medical consultation website, Taiwan eDoctor. Five research themes are explored: (1) length of questions, (2) moment of seeking consultation, (3) strategies of communicating chief complaints, (4) purpose of seeking consultation and (5) identity disclosure. METHODS: Data collection was conducted by randomly selecting 50 resolved consultation Q&As for each of 24 medical specialties, resulting in a total of 1200 entries in the primary data set. Data analysis was conducted qualitatively and quantitatively. RESULTS: Average length of questions was 161.21 words. Online medical consultation was sought when healthy, healthy but not robust, when suspicious of illness, when diagnosed as ill and during treatment/recovery. In communicating chief complaints, consultation seekers were engaged in contextual, focal or emotional communication styles. Nine distinct purposes to seek online consultation were identified and can be broadly interpreted as intellectual, social and emotional. The finding also suggests that more than two-third of questions were asked for by the patients themselves. CONCLUSION: Through content analysis of questions posted on an online medical consultation website, this study characterises communication patterns during the health information seeking process. These findings can help guide the design of more effective patient-centred online medical consultation services. PMID- 27380769 TI - Factors impacting on menstrual hygiene and their implications for health promotion. AB - BACKGROUND: In the lives of women, puberty is marked by the onset of menarche. From this stage onwards until menopause, reproductive health and menstrual hygiene are important aspects of women's lives. In Zambia's Western Province, the natural process of menstruation is a taboo and dealt with secretly. Information and knowledge about menstruation and menstrual hygiene among adolescent girls is inadequate. This paper explores the factors influencing the understanding, experiences and practices of menstrual hygiene among adolescent girls in Mongu District, Western Province of Zambia. METHODS: An explorative study design was used by means of six focus group discussions conducted with 51 respondents, aged 13-20 years, from three secondary schools. Their age at menarche was 11-15. For data analysis thematic content analysis was used. RESULTS: The paper shows that the girls suffer from poor menstrual hygiene, originating from lack of knowledge, culture and tradition, and socio-economic and environmental constraints, leading to inconveniences, humiliation and stress. This leads to reduced school attendance and poor academic performance, or even drop outs, and ultimately infringes upon the girls' human rights. CONCLUSION: To address these shortcomings, a 'super setting approach' is recommended, in which a Health Promoting School could improve the girls' individual and group needs, and a community setting which would address the broader socio-economic, cultural and environmental conditions. This would enable creating a supportive environment for the girls to manage their periods. To successfully utilize the approach, all stakeholders (parents, teachers, children, governments and communities) should cooperate to generate context-specific solutions for creating safe menstrual care, and better and dignified conditions for adolescent girls. Therefore, this calls for comprehensive, strident advocacy for policy changes at national level, and mediation and involvement at community level. PMID- 27380770 TI - NHS funding at serious risk from Brexit, think tank warns. PMID- 27380771 TI - Rescue of endemic states in interconnected networks with adaptive coupling. AB - We study the Susceptible-Infected-Susceptible model of epidemic spreading on two layers of networks interconnected by adaptive links, which are rewired at random to avoid contacts between infected and susceptible nodes at the interlayer. We find that the rewiring reduces the effective connectivity for the transmission of the disease between layers, and may even totally decouple the networks. Weak endemic states, in which the epidemics spreads when the two layers are interconnected but not in each layer separately, show a transition from the endemic to the healthy phase when the rewiring overcomes a threshold value that depends on the infection rate, the strength of the coupling and the mean connectivity of the networks. In the strong endemic scenario, in which the epidemics is able to spread on each separate network -and therefore on the interconnected system- the prevalence in each layer decreases when increasing the rewiring, arriving to single network values only in the limit of infinitely fast rewiring. We also find that rewiring amplifies finite-size effects, preventing the disease transmission between finite networks, as there is a non zero probability that the epidemics stays confined in only one network during its lifetime. PMID- 27380772 TI - Wellens syndrome, a predictor of critical left anterior descending artery stenosis. PMID- 27380773 TI - Atypical clinical presentation of primary and secondary cutaneous follicle center lymphoma (FCL) on the head characterized by macular lesions. AB - BACKGROUND: Primary cutaneous follicle center lymphoma (pcFCL) usually presents with reddish nodules, plaques, and tumors on the head and neck or the back. OBJECTIVE: We sought to describe a peculiar clinical presentation of pcFCL and secondary cutaneous follicle center lymphoma (FCL). METHODS: We report a series of 13 patients (7 male and 6 female; median age 58 years, mean age 58.2 years, age range 26-83 years) with either pcFCL (11 patients) or secondary cutaneous FCL (2 patients) presenting with lesions on the head deviating from the classic clinical manifestations characterized by plaques and tumors. RESULTS: All patients presented clinically with diffuse, ill-defined, partly hypochromic, partly erythematous macules or with inconspicuous lesions located predominantly on the scalp and forehead. Dimension ranged between 4 to 5 cm2 and greater than 30 cm2. The initial diagnosis was never cutaneous lymphoma, and all patients received various diagnoses including rosacea, alopecia, erysipelas, discoid lupus erythematosus, angiosarcoma, Borrelia infection, or sarcoidosis. Histologic examination confirmed the diagnosis of FCL in all patients. LIMITATIONS: Small number of cases and retrospective study design are limitations. CONCLUSIONS: This clinical presentation of both pcFCL and secondary cutaneous FCL is unusual and represents a pitfall in the clinical diagnosis. Dermatologists should be aware of this clinical variant of FCL to establish a timely diagnosis and treat patients properly. PMID- 27380774 TI - Intergenerational policy and workforce participation in Australia: using health as a metric. AB - Like many nations, population ageing is challenging Australia's economic future; increasing the workforce participation of mothers and mature-aged adults are two policy strategies to address it. Drawing on a Health in All Policies (HiAPs) framework, our study aims to supply longitudinal evidence on connections between this policy strategy and health. Considering physical inactivity, poor mental health, overweight and obesity we estimate associations with the level of participation (not employed compared with part- or full-time employed). Using eight waves of data from the Household, Income and Labour Dynamics in Australia survey, a series of random intercept logistic models estimate the odds for mothers (n = 2105) and Australians aged 55-64 years (n = 3201) on each health outcome. We find that there are health benefits as well as risks linked to level of participation. Mothers who worked >20 h/wk had higher odds of physical inactivity, as did mature-aged Australians working either part - or full-time. Working part- or full-time was unrelated to overweight or obesity over the span of our study. Level of participation was unrelated to mental health among mature age Australians, although part-time (but not full-time) work benefited mothers'. In terms of health, working more may offer mixed blessings to these two target populations; part-time work appears to be optimal. By using health as a metric, our study adds to the case for a HiAPs approach. PMID- 27380776 TI - Labour migration of Polish nurses: a questionnaire survey conducted with the Computer Assisted Web Interview technique. AB - BACKGROUND: According to data from the Organisation for Economic Cooperation and Development, Poland has one of the lowest numbers of nurses (5.2) per 1000 inhabitants among 28 EU countries. The migration of nurses from Poland has particular importance in the context of scarce human resources in this professional group, especially given the increasingly ageing population in European societies, which will entail an increased demand for nursing and care services. The aim of the study was to obtain information on the intentions of Polish nurses to migrate for work to other countries in the European region. METHODS: The study included 581 nurses, professionally active in Poland over the duration of the study. The Computer Assisted Web Interview technique was used to collect data. Nurses filled in a web-based questionnaire that was available from December 5, 2011, to March 5, 2012. The choice of respondents for the sample was based on the availability of data. An invitation to participate in the study could be viewed on selected websites from the Portal of Nurses and Midwives, the Supreme Chamber of Nurses and Midwives, and the Polish Nursing Society. The survey questionnaire was designed by the authors, which served as the primary research tool. RESULTS: Nearly one in three respondents intended to leave Poland for professional reasons. Overall, 12.4 % of respondents had already worked as a nurse abroad. The main destinations for migration included Germany, followed by England and Norway. The intended length of stay abroad ranged from 2-5 years. CONCLUSIONS: In the studied group of Polish nurses, there was great interest in seeking employment abroad. Nurses tend to go abroad mostly for long-term, repeated periods to the wealthiest countries nearest to Poland. In view of the low level of human resources in the Polish nursing sector, the migration of Polish nurses will probably have crucial implications for the quality of healthcare services in Poland in the coming years. Given the methodology applied, study findings refer solely to the study group. PMID- 27380775 TI - Global identification of hnRNP A1 binding sites for SSO-based splicing modulation. AB - BACKGROUND: Many pathogenic genetic variants have been shown to disrupt mRNA splicing. Besides splice mutations in the well-conserved splice sites, mutations in splicing regulatory elements (SREs) may deregulate splicing and cause disease. A promising therapeutic approach is to compensate for this deregulation by blocking other SREs with splice-switching oligonucleotides (SSOs). However, the location and sequence of most SREs are not well known. RESULTS: Here, we used individual-nucleotide resolution crosslinking immunoprecipitation (iCLIP) to establish an in vivo binding map for the key splicing regulatory factor hnRNP A1 and to generate an hnRNP A1 consensus binding motif. We find that hnRNP A1 binding in proximal introns may be important for repressing exons. We show that inclusion of the alternative cassette exon 3 in SKA2 can be significantly increased by SSO-based treatment which blocks an iCLIP-identified hnRNP A1 binding site immediately downstream of the 5' splice site. Because pseudoexons are well suited as models for constitutive exons which have been inactivated by pathogenic mutations in SREs, we used a pseudoexon in MTRR as a model and showed that an iCLIP-identified hnRNP A1 binding site downstream of the 5' splice site can be blocked by SSOs to activate the exon. CONCLUSIONS: The hnRNP A1 binding map can be used to identify potential targets for SSO-based therapy. Moreover, together with the hnRNP A1 consensus binding motif, the binding map may be used to predict whether disease-associated mutations and SNPs affect hnRNP A1 binding and eventually mRNA splicing. PMID- 27380777 TI - Primary stability of a shoulderless Zweymuller hip stem: a comparative in vitro micromotion study. AB - BACKGROUND: The Zweymuller stem design has proven long-term stability with a 20 year survival rate of over 90 %. Primary stability necessitates implant-bone micromotions below 150 MUm, otherwise bony ingrowth is negatively influenced. METHODS: Using fresh paired human femurs, we investigated a modification of the Zweymuller-type stem design with reduced proximal lateral shoulder in reference to primary stability. Relative motion between the implant and the cortical bone as well as the irreversible implant migration was investigated under dynamic loading (100-1600 N) over 100,000 cycles using miniature displacement transducers. RESULTS: Micromotions were below the critical threshold for both implants at all measurement points. Axial reversible and irreversible micromotions were not influenced by reducing the shoulder of the prosthesis. Resistance against rotational moments was less pronounced after reduction of the shoulder without statistical significant results. CONCLUSIONS: Reducing the proximal shoulder of the Zweymuller-type stem design does not negatively influence axial stability but might negatively influence rotational stability. Even though, comparable results still suggest a reasonable resistance against rotational forces. PMID- 27380778 TI - Perceptions of Successful Ageing Among Iranian Elders: Insights From a Qualitative Study. AB - The aim of this article is to explore the perceptions of successful ageing among Iranian elderly. The data were collected in Tehran city on 60 older adults using a semistructured interview. The collected data were analyzed using directed content analysis. The findings revealed various dimensions of successful ageing among Iranian older adults. Social well-being is the most prevalent dimension of successful ageing, followed by psychological well-being, physical health, spirituality and transcendence, financial security, and an elder-friendly environmental and social context. Also, the findings from this study provide a new understanding of successful ageing in the context of Iran and contribute additional elements. This qualitative study highlights the importance of multidimensional and contextual viewpoints to successful ageing. In conclusion, to achieve multidimensional successful ageing, the interaction between all levels of successful ageing such as individual, family, and environment must be considered. PMID- 27380779 TI - Self-Reported Ageism Across the Lifespan: Role of Aging Knowledge. AB - The authors examined the prevalence of self-reported ageist behaviors in a lifespan sample ranging in age from 13 to 91 years. Participants completed the Relating to Older People Evaluation (Cherry & Palmore). Results indicated that adolescents and young adults reported fewer ageist behaviors overall than did middle-aged and older adults. Positive ageist behaviors were more frequent than negative ageist behaviors for people of all ages. Women endorsed positive ageism items more often than men, although men and women did not differ in frequency of negative ageist behaviors. Follow-up analyses on participants' responses to two knowledge of aging measures, the Facts on Aging Quiz and the Knowledge of Memory Aging Questionnaire, showed that knowledge of aging was significantly correlated with negative ageist behaviors, after controlling for age and gender. Implications of these findings for current views of ageism (positive and negative) are discussed. PMID- 27380780 TI - Understanding Adult Age Differences in the Frequency of Problems With Friends. AB - We investigated characteristics of younger and older adults' friendships. Younger (N = 39) and older (N = 39) adults completed measures pertaining to a specific friend they had (i.e., contact frequency, positive friendship quality, and negative friendship quality) and their frequency of problems with friends in general. Older adults reported fewer problems with friends in general, and fewer negative friendship qualities, less frequent contact, and more positive friendship qualities with a specific friend than younger adults. Contact frequency, positive friendship quality, and negative friendship quality with a specific friend were related to frequency of problems with friends in general, but only contact frequency was a significant mediator of the relation between age and frequency of problems with friends in general. Results show that characteristics of a specific friendship relate to problems with friends in general, and that contact frequency with a specific friend mediates the relation between age and problems with friends in general. Implications are discussed. PMID- 27380781 TI - Postgraduate training for family medicine in a rural district hospital in South Africa: Appropriateness and sufficiency of theatre procedures as a sentinel indicator. AB - BACKGROUND: Since 2007, the postgraduate training of family physicians for South African district hospitals has been formalised. This training differs from European and North American programmes as up to 30% of the skills needed rely on district hospital surgical, obstetrics and anaesthetics procedures, particularly in rural areas, as outlined in the national unit standards. The aim of this study was to evaluate the appropriateness and sufficiency of learning opportunities for these skills in a rural district hospital. METHODS: A descriptive, cross sectional study was undertaken of the number and type of procedures performed in theatre for a 1-year period and compared with the required procedural skills stipulated in the national unit standards. Descriptive statistical analyses were used to analyse categorical data. RESULTS: Three thousand seven hundred and forty one procedures were performed during the study period. Anaesthesia was the most common procedure, followed by Caesarean section. There were adequate opportunities for teaching most core skills. CONCLUSIONS: Sufficient and appropriate learning opportunities exist for postgraduate family medicine training in all the core skills performed in a theatre according to the national unit standards. PMID- 27380782 TI - Chest pain prevalence, causes, and disposition in the emergency department of a regional hospital in Pretoria. AB - BACKGROUND: Chest pain is a common clinical syndrome. However, there is a paucity of African studies describing the causes, prevalence, aetiology, and disposition of patients with chest pain presenting in the emergency department (ED). AIM: The aim of this retrospective descriptive study was to determine the prevalence, causes, demographics, and disposition of all adult patients with the main complaint of chest pain presenting at the ED of a regional hospital in South Africa. METHODS: Records of all patients 18 years and older presenting with the complaint of chest pain from 1 December 2011 through 10 April 2012 were assessed. A data collection sheet capturing patient demographics and disposition from the ED was used. The diagnosis was subdivided into groups: cardiovascular, respiratory, gastrointestinal, musculoskeletal, psychiatric/psychogenic, other, and unknown. RESULTS: Of the 312 patients presenting with chest pain, 210 patient files were retrieved. The prevalence of non-traumatic chest pain was 1.66%. Respiratory disease was the most common cause (36.19%), with pneumonia the most common diagnosis (24.40%). Logistic regression showed diagnoses of acute cardiovascular disease or respiratory disease, older age, and transport by ambulance as being associated with admission. CONCLUSION: The main cause of acute chest pain was found to be respiratory disease, followed by musculoskeletal disorders. In the African context, the aetiology of acute chest pain differs from that in first world countries. Health workers should therefore pay special attention to respiratory conditions during diagnosis and management in African patients with acute chest pain. PMID- 27380783 TI - Rural exposure during medical education and student preference for future practice location - a case of Botswana. AB - BACKGROUND: Botswana's medical school graduated its first class in 2014. Given the importance of attracting doctors to rural areas the school incorporated rural exposure throughout its curriculum. AIM: This study explored the impact of rural training on students' attitudes towards rural practice. SETTING: The University of Botswana family medicine rural training sites, Maun and Mahalapye. METHODS: The study used a mixed-methods design. After rural family medicine rotations, third- and fifth-year students were invited to complete a questionnaire and semi structured interview. Data were analysed using descriptive statistics and thematic analysis. RESULTS: The thirty-six participants' age averaged 23 years and 48.6% were male. Thirtythree desired urban practice in a public institution or university. Rural training did not influence preferred future practice location. Most desired specialty training outside Botswana but planned to practice in Botswana. Professional stagnation, isolation, poorly functioning health facilities, dysfunctional referral systems, and perceived lack of learning opportunities were barriers to rural practice. Lack of recreation and poor infrastructure were personal barriers. Many appreciated the diversity of practice and supportive staff seen in rural practice. Several considered monetary compensation as an enticement for rural practice. Only those with a rural background perceived proximity to family as an incentive to rural practice. CONCLUSION: The majority of those interviewed plan to practice in urban Botswana, however, they did identify factors that, if addressed, may increase rural practice in the future. Establishing systems to facilitate professional development, strengthening specialists support, and deploying doctors near their home towns are strategies that may improve retention of doctors in rural areas.Keyords: rural health, student perceptions. PMID- 27380785 TI - Insights of private general practitioners in group practice on the introduction of National Health Insurance in South Africa. AB - BACKGROUND: The South African government intends to contract with 'accredited provider groups' for capitated primary care under National Health Insurance (NHI). South African solo general practitioners (GPs) are unhappy with group practice. There is no clarity on the views of GPs in group practice on contracting to the NHI. OBJECTIVES: To describe the demographic and practice profile of GPs in group practice in South Africa, and evaluate their views on NHI, compared to solo GPs. METHODS: This was a descriptive survey. The population of 8721 private GPs in South Africa with emails available were emailed an online questionnaire. Descriptive statistical analyses and thematic content analysis were conducted. RESULTS: In all, 819 GPs responded (568 solo GPs and 251 GPs in groups). The results are focused on group GPs. GPs in groups have a different demographic practice profile compared to solo GPs. GPs in groups expected R4.86 million ($0.41 million) for a hypothetical NHI proposal of comprehensive primary healthcare (excluding medicines and investigations) to a practice population of 10 000 people. GPs planned a clinical team of 8 to 12 (including nurses) and 4 to 6 administrative staff. GPs in group practices saw three major risks: patient, organisational and government, with three related risk management strategies. CONCLUSIONS: GPs can competitively contract with NHI, although there are concerns. NHI contracting should not be limited to groups. All GPs embraced strong teamwork, including using nurses more effectively. This aligns well with the emergence of family medicine in Africa. PMID- 27380786 TI - Knowledge of symptoms and self-management of hypoglycaemia amongst patients attending a diabetic clinic at a regional hospital in KwaZulu-Natal. AB - BACKGROUND: Diabetic patients on insulin and sulphonylureas are at risk of developing hypoglycaemia. Many patients do not respond appropriately because of poor knowledge and understanding of the symptoms of hypoglycaemia, which if not promptly treated can lead to permanent neurological and renal damage. Hypoglycaemic complications can be avoided if patients have a good knowledge of the early symptoms of hypoglycaemia and know how to respond appropriately. AIM: The aim of this study was to assess the knowledge of adult diabetic patients attending a diabetic clinic about symptoms of hypoglycaemia and how they responded to these symptoms. SETTING: A hospital-based diabetic clinic in northern KwaZulu-Natal. METHODS: This was a cross-sectional, descriptive study involving 200 diabetic patients. Demographic data and details of current medication, knowledge of hypoglycaemia and how patients responded to the symptoms were collected using a validated questionnaire. RESULTS: The majority of the patients had fair to good knowledge of hypoglycaemia; however, less than 25% knew what action to take when they experienced symptoms suggestive of hypoglycaemia. CONCLUSION: There is a need to improve the education given to diabetic patients on stepwise measures to take to avoid life-threatening complications associated with hypoglycaemia. PMID- 27380784 TI - Non-communicable disease risk factors and treatment preference of obese patients in Cape Town. AB - BACKGROUND: Insights into the characteristics of treatment seekers for lifestyle changes and treatment preferences are necessary for intervention planning. AIM: To compile a profile of treatment-seeking obese patients with non-communicable diseases (NCDs) or NCD risk factors and to compare patients who choose group based (facility-based therapeutic group [FBTG]) versus usual care (individual consultations) treatment. SETTING: A primary healthcare facility in Cape Town, South Africa. METHODS: One hundred and ninety-three patients were recruited in this cross-sectional study. Ninety six chose FBTG while 97 chose usual care. A questionnaire, the hospital database and patients' folders were used to collect data. Weight, height and waist circumference were measured. STATA 11.0 was used for descriptive statistics and to compare the two groups. RESULTS: The subjects' mean age was 50.4 years, 78% were women and of low education levels and income, and 41.5% had type 2 diabetes, 83.4% hypertension and 69.5% high cholesterol. Mean (s.d.) HbA1c was 9.1 (2.0)%, systolic BP 145.6 (21.0) mmHg, diastolic BP 84.5 (12.0) mmHg, cholesterol 5.4 (1.2) mmol/L), body mass indicator (BMI) 39.3 (7.3) kg/m2 and waist circumference 117 (12.6) cm). These figures were undesirable although pharmacological treatment for diabetes and hypertension was in place. Only 14% were physically active, while TV viewing was > 2h/day. Mean daily intake of fruit and vegetables (2.2 portions/day) was low while added sugar (5 teaspoons) and sugar-sweetened beverages (1.3 glasses) were high. Usual care patients had a higher smoking prevalence, HbA1c, number of NCD risk factors and refined carbohydrate intake, and a lower fruit and vegetable intake. CONCLUSION: Treatment seekers were typically middle-aged, low income women with various modifiable and intermediate risk factors for NCDs. Patients choosing usual care could have more NCD risks. PMID- 27380787 TI - Doctors' views of disulfiram and their response to relapse in alcohol-dependent patients, Free State, 2009. AB - BACKGROUND: Disulfiram is the oldest and best known drug to prevent relapse after detoxification from alcohol. Effective use of the drug is dependent on stringent monitoring and high levels of external motivation. Doctors' perceptions about the drug have not been investigated extensively. AIM: We investigated the perceptions and practices of doctors involved in relapse prevention in alcoholics with regard to disulfiram and their response to relapse. SETTING: The study population consisted of 60 doctors from the Free State Province, involved in the follow-up of alcoholics across various work settings. METHODS: A cross-sectional descriptive study design was used, and data collection involved the use of a questionnaire and semi-structured interviews. Quantitative results are presented in figures and percentages to provide a background for the qualitative findings that are clustered in themes. RESULTS: A quarter of participants did not prescribe disulfiram, another quarter prescribed disulfiram routinely after detoxification, and half of them prescribed it for selected cases only. Subject to affordability, selection of disulfiram was mainly determined by the perceived level of the patient's motivation. External motivation sometimes took the form of threats of bodily harm or death caused by drinking. Some participants regarded relapse as confirmation of poor motivation and even a valid reason for terminating the doctor-patient relationship. CONCLUSION: Doctors perceive disulfiram as a psychological tool to induce motivation through creating fear of drinking. Failure and success are perceived as related to the level of motivation. These perceptions could be unfair as biological factors in inter patient variability in response are ignored. PMID- 27380788 TI - Patients' perceptions of the triage system in a primary healthcare facility, Cape Town, South Africa. AB - BACKGROUND: In public healthcare facilities, where the patient numbers and the available resources are often disproportionate, triage is used to prioritise when patients are seen. Patients may not understand the triage process and have strong views on how to improve their experience. AIM: This study explored the views of patients who had undergone triage in the emergency centre of a primary care facility. SETTING: Gugulethu Community Health Centre, Cape Town. METHODS: A purposive sample consisted of five women (one coded green, three orange, one yellow) and four men (one coded green and three yellow). A semi-structured qualitative interview was conducted in either Xhosa or English and the transcripts analysed using the framework method. RESULTS: All of the respondents complained of a lack of information and poor understanding of the triage process. Those coded green experienced the process as biased and unfair and reported that the triage nurse was rude and unprofessional. By contrast, those coded yellow or orange found the triage nurse to be helpful and professional. Most patients turned to support staff (e.g. security staff or cleaners) for assistance in dealing with the triage system. Most patients waited longer than the guidelines recommend and the green-coded patients complained about this issue. CONCLUSION: Patients did not have a good experience of the triage system. Managers of the triage system need to design better strategies to improve patient acceptance and share information. The important role of support staff needs to be recognised and strengthened. PMID- 27380789 TI - Multidrug-resistant tuberculosis in KwaZulu-Natal, South Africa: An overview of patients' reported knowledge and attitudes. AB - BACKGROUND: The incidence and prevalence of multidrug-resistant tuberculosis (MDR TB) in the province of KwaZulu-Natal, South Africa, are amongst the highest in the world. Previously, interventions have been largely biomedical based; however, there is growing opinion that interventions must include social aspects such as patient education and attitudes. METHODS: This observational study assessed the knowledge and attitudes of 380 patients diagnosed with MDR TB at a centralised MDR TB unit in Durban. Data were collected using a questionnaire that was distributed to every third patient attending the outpatient MDR TB clinic. Data were collected over an 8-week period and analysed descriptively. RESULTS: Just under half of the respondents had primary MDR TB. Most respondents were young, female unemployed and did not receive a social grant. Knowledge around diagnosis of MDR TB was generally adequate. There were important misconceptions about spread of the disease and duration of treatment. Most respondents received knowledge of MDR TB from healthcare workers. Some respondents received knowledge from friends, family and Sangomas and believed that the disease was caused by bewitchment or as a form of punishment. DISCUSSION: The need for strengthening the role of primary care physicians in promoting education and providing support is highlighted. Further study is needed to investigate the high rate of primary MDR TB and to identify the unique challenges faced by women who have MDR TB. Future research could include the possibility of involving traditional healers in a contextually sensitive MDR TB education, training and support programme. PMID- 27380790 TI - A review of hypoglycaemia in a South African family practice setting. AB - BACKGROUND: The prevalence and incidence of diabetes in South Africa are high and are expected to increase. Mortality and morbidity may be related to hypoglycaemia, and there is limited information on hypoglycaemia from private practice sites. The aim of this study was to assess patients' education about, knowledge of and response to hypoglycaemia. METHODS: The study site was a general practice, and participants were all patients with diabetes who presented to the practice over a 1-month period. Data were collected using a closedended questionnaire and analysed descriptively. FINDINGS: Most respondents were South Africans of Indian origin and were diagnosed with diabetes at a relatively young age. Despite attending a private practice, most had low incomes and low schooling levels. Just under half reported having experienced hypoglycaemia, and there was a strong association between hypoglycaemia and insulin use. Many reported never having received any education around hypoglycaemia. DISCUSSION: The study highlights the need for early screening for diabetes in this vulnerable population. Hypoglycaemic education should consider low schooling levels even in a private general practice, and further study is required on the quality and frequency of education provided in general practice. PMID- 27380791 TI - Cytomegalovirus-Associated Menetrier Disease in Childhood. PMID- 27380792 TI - Family fIRST, an Interactive Risk Screening Tool for Families in a School-Based Pediatric Clinic. AB - The purpose of this study was to create a tablet-based, social history screening tool called Family fIRST and evaluate its feasibility and usability in a school based medical clinic. A mixed methods study design was used to examine quantitative and qualitative outcomes of a survey and semi-structured interview completed by families and physicians. The majority (87%) found the survey easy to understand. Themes for improvement included more free-form space and increased sensitivity around question wording. Clinic physicians felt Family fIRST increased discussion around social history and suggested the tool should help link to suggested resources. Demographic results showed that 12 of 29 (43%) parents had income less than $15 000 and 19 of 29 (65%) were unemployed. Family fIRST was a well-received and feasible tool to implement at the school-based medical clinic. Preliminary results show that families attending the clinic have increased prevalence of negative determinants of health; social history should therefore represent a key area of focus at the medical visit in order to optimize clinic support of families. PMID- 27380793 TI - Population-Based Study of Incidence and Antimicrobial Resistance Patterns of Extraintestinal Escherichia coli Infections in Children in Olmsted County, Minnesota, 2012. PMID- 27380794 TI - Cohort Profile: The Australian Gulf War Veterans' Health Study cohort. PMID- 27380795 TI - Cohort Profile: The European Longitudinal Study of Pregnancy and Childhood (ELSPAC) in the Czech Republic. PMID- 27380796 TI - Data Resource Profile: The Korea Youth Risk Behavior Web-based Survey (KYRBS). PMID- 27380797 TI - Vaccinations against smallpox and tuberculosis are associated with better long term survival: a Danish case-cohort study 1971-2010. AB - Background: When vaccinations with vaccinia against smallpox and Bacillus Calmette-Guerin (BCG) against tuberculosis were phased out in some high-income countries around 1980, the impact on overall mortality was not examined. Recent studies from low-income countries have suggested that these vaccines are associated with mortality reductions, not explained by specific disease protection. We examined whether vaccinia and BCG administered in childhood were associated with long-term mortality reductions in a high-income population. Methods: In this case-cohort study, we followed 47 622 schoolchildren from Copenhagen, Denmark, born 1965 to 1976, from their first health examination to 2010. This cohort experienced the phase-out of vaccinia and BCG vaccination programmes. Results: A sub-cohort of 5 316 individuals (699 excluded) was followed for 164 450 person-years (0.2% were lost to follow-up), and 401 deaths due to natural causes (841 deaths in total) occurred in the full cohort. Compared with individuals who had not received vaccinia or BCG, those who had received both vaccinia and BCG had an adjusted hazard ratio (aHR) of 0.54 [95% confidence interval (CI): 0.36-0.81] for mortality due to natural causes of death; those who only received BCG had an aHR of 0.58 (95% CI: 0.39-0.85). Vaccinia and BCG were not associated with any protection against deaths by accidents, suicide or murder, the combined aHR being 0.94 (95% CI: 0.62-1.42). Conclusions: Vaccinia and BCG vaccinations were associated with better long-term survival, which was not explained by specific protection. Vaccines with beneficial non-specific effects may reduce overall mortality even after the target diseases are eradicated. PMID- 27380798 TI - Reciprocal Reinforcement Between Wearable Activity Trackers and Social Network Services in Influencing Physical Activity Behaviors. AB - BACKGROUND: Wearable activity trackers (WATs) are emerging consumer electronic devices designed to support physical activities (PAs), which are based on successful behavior change techniques focusing on goal-setting and frequent behavioral feedbacks. Despite their utility, data from both recent academic and market research have indicated high attrition rates of WAT users. Concurrently, evidence shows that social support (SS), delivered/obtained via social network services or sites (SNS), could increase adherence and engagement of PA intervention programs. To date, relatively few studies have looked at how WATs and SS may interact and affect PAs. OBJECTIVE: The purpose of this study was to explore how these two Internet and mobile technologies, WATs and SNS, could work together to foster sustainable PA behavior changes and habits among middle-aged adults (40-60 years old) in Taiwan. METHODS: We used purposive sampling of Executive MBA Students from National Taiwan University of Science and Technology to participate in our qualitative research. In-depth interviews and focus groups were conducted with a total of 15 participants, including 9 WAT users and 6 nonusers. Analysis of the collected materials was done inductively using the thematic approach with no preset categories. Two authors from different professional backgrounds independently annotated and coded the transcripts, and then discussed and debated until consensus was reached on the final themes. RESULTS: The thematic analysis revealed six themes: (1) WATs provided more awareness than motivation in PA with goal-setting and progress monitoring, (2) SS, delivered/obtained via SNS, increased users' adherence and engagement with WATs and vice versa, (3) a broad spectrum of configurations would be needed to deliver WATs with appropriately integrated SS functions, (4) WAT design, style, and appearance mattered even more than those of smartphones, as they are body worn devices, (5) the user interfaces of WATs left a great deal to be desired, and (6) privacy concerns must be addressed before more mainstream consumers would consider adopting WATs. CONCLUSIONS: Participants perceived WATs as an awareness tool to understand one's PA level. It is evident from our study that SS, derived from SNS and other pertinent vehicles such as the LINE social messaging application (similar to WhatsApp and WeChat), will increase the engagement and adherence of WAT usage. Combining WATs and SNS enables cost-effective, scalable PA intervention programs with end-to-end services and data analytics capabilities, to elevate WATs from one-size-fits-all consumer electronics to personalized PA assistants. PMID- 27380799 TI - Carbon-ion pencil beam scanning for thoracic treatment - initiation report and dose metrics evaluation. AB - Carbon-ion beam scanning has not previously been used for moving tumor treatments. We have commenced respiratory-gated carbon-ion radiotherapy (CIRT) in the thoracic and abdominal regions under free-breathing conditions as a clinical trial. This study aimed to investigate this treatment in the lungs in comparison with passive scattering CIRT. Five patients had thoracic tumors treated with carbon-ion scanned beams using respiratory gating. We analyzed the actual treatments and calculated passive scattering treatment plans based on the same planning CT. We evaluated tumor size until 3 months post treatment and each treatment plan regarding dose delivered to 95% of the clinical target volume (CTV D95), mean lung dose, percentage of lung receiving at least 5 Gy (RBE) (Lung-V5), Lung-V10, Lung-V20, heart maximum dose (Dmax), esophagus Dmax, cord Dmax and skin Dmax. Obvious tumor deterioration was not observed up to 3 months post treatment. The dose evaluation metrics were similar item by item between respiratory-gated scanned CIRT and passive scattering CIRT. In conclusion, scanned beam CIRT provided treatments equivalent to passive scattering CIRT for thoracic tumors. Increased sample numbers and longer-term observation are needed. PMID- 27380800 TI - Whole-pelvic radiotherapy with spot-scanning proton beams for uterine cervical cancer: a planning study. AB - The aim of this study was to compare the dosimetric parameters of whole-pelvic radiotherapy (WPRT) for cervical cancer among plans involving 3D conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), or spot-scanning proton therapy (SSPT). The dose distributions of 3D-CRT-, IMRT-, and SSPT-based WPRT plans were compared in 10 patients with cervical cancer. All of the patients were treated with a prescribed dose of 50.4 Gy in 1.8-Gy daily fractions, and all of the plans involved the same planning target volume (PTV) constrictions. A 3D CRT plan involving a four-field box, an IMRT plan involving seven coplanar fields, and an SSPT plan involving four fields were created. The median PTV D95% did not differ between the 3D-CRT, IMRT and SSPT plans. The median conformity index 95% and homogeneity index of the IMRT and SSPT were better than those of the 3D-CRT. The homogeneity index of the SSPT was better than that of the IMRT. SSPT resulted in lower median V20 values for the bladder wall, small intestine, colon, bilateral femoral heads, skin, and pelvic bone than IMRT. Comparing the Dmean values, SSPT spared the small intestine, colon, bilateral femoral heads, skin and pelvic bone to a greater extent than the other modalities. SSPT can reduce the irradiated volume of the organs at risk compared with 3D-CRT and IMRT, while maintaining excellent PTV coverage. Further investigations of SSPT are warranted to assess its role in the treatment of cervical cancer. PMID- 27380801 TI - A calibration method for realistic neutron dosimetry in radiobiological experiments assisted by MCNP simulation. AB - Many studies on biological effects of neutrons involve dose responses of neutrons, which rely on accurately determined absorbed doses in the irradiated cells or living organisms. Absorbed doses are difficult to measure, and are commonly surrogated with doses measured using separate detectors. The present work describes the determination of doses absorbed in the cell layer underneath a medium column (DA) and the doses absorbed in an ionization chamber (DE) from neutrons through computer simulations using the MCNP-5 code, and the subsequent determination of the conversion coefficients R (= DA/DE). It was found that R in general decreased with increase in the medium thickness, which was due to elastic and inelastic scattering. For 2-MeV neutrons, conspicuous bulges in R values were observed at medium thicknesses of about 500, 1500, 2500 and 4000 MUm, and these were attributed to carbon, oxygen and nitrogen nuclei, and were reflections of spikes in neutron interaction cross sections with these nuclei. For 0.1-MeV neutrons, no conspicuous bulges in R were observed (except one at ~2000 MUm that was due to photon interactions), which was explained by the absence of prominent spikes in the interaction cross-sections with these nuclei for neutron energies <0.1 MeV. The ratio R could be increased by ~50% for small medium thickness if the incident neutron energy was reduced from 2 MeV to 0.1 MeV. As such, the absorbed doses in cells (DA) would vary with the incident neutron energies, even when the absorbed doses shown on the detector were the same. PMID- 27380802 TI - The impact of emphysema on dosimetric parameters for stereotactic body radiotherapy of the lung. AB - The purpose of this study was to evaluate the impact of emphysematous changes in lung on dosimetric parameters in stereotactic body radiation therapy (SBRT) for lung tumor. A total of 72 treatment plans were reviewed, and dosimetric factors [including homogeneity index (HI) and conformity index (CI)] were evaluated. Emphysematous changes in lung were observed in 43 patients (60%). Patients were divided into three groups according to the severity of emphysema: no emphysema (n = 29), mild emphysema (n = 22) and moderate to severe emphysema groups (n = 21). The HI (P < 0.001) and the CI (P = 0.029) were significantly different in accordance with the severity of emphysema in one-way analysis of variance (ANOVA). The HI value was significantly higher in the moderate to severe emphysema group compared with in the no emphysema (Tukey, P < 0.001) and mild emphysema groups (P = 0.002). The CI value was significantly higher in the moderate to severe emphysema group compared with in the no emphysema group (P = 0.044). In multiple linear regression analysis, the severity of emphysema (P < 0.001) and the mean material density of the lung within the PTV (P < 0.001) were significant factors for HI, and the mean density of the lung within the PTV (P = 0.005) was the only significant factor for CI. The mean density of the lung within the PTV was significantly different in accordance with the severity of emphysema (one-way ANOVA, P = 0.008) and the severity of emphysema (P < 0.001) was one of the significant factors for the density of the lung within the PTV in multiple linear regression analysis. Our results suggest that emphysematous changes in the lung significantly impact on several dosimetric parameters in SBRT, and they should be carefully evaluated before treatment planning. PMID- 27380803 TI - Dependence and independence of survival parameters on linear energy transfer in cells and tissues. AB - Carbon-ion radiotherapy has been used to treat more than 9000 cancer patients in the world since 1994. Spreading of the Bragg peak is necessary for carbon-ion radiotherapy, and is designed based on the linear-quadratic model that is commonly used for photon therapy. Our recent analysis using in vitro cell kills and in vivo mouse tissue reaction indicates that radiation quality affects mainly the alpha terms, but much less the beta terms, which raises the question of whether this is true in other biological systems. Survival parameters alpha and beta for 45 in vitro mammalian cell lines were obtained by colony formation after irradiation with carbon ions, fast neutrons and X-rays. Relationships between survival parameters and linear energy transfer (LET) below 100 keV/MUm were obtained for 4 mammalian cell lines. Mouse skin reaction and tumor growth delay were measured after fractionated irradiation. The Fe-plot provided survival parameters of the tissue reactions. A clear separation between X-rays and high LET radiation was observed for alpha values, but not for beta values. Alpha values/terms increased with increasing LET in any cells and tissues studied, while beta did not show a systematic change. We have found a puzzle or contradiction in common interpretations of the linear-quadratic model that causes us to question whether the model is appropriate for interpreting biological effectiveness of high-LET radiation up to 500 keV/MUm, probably because of inconsistency in the concept of damage interaction. A repair saturation model proposed here was good enough to fit cell kill efficiency by radiation of wide ranged LET. A model incorporating damage complexity and repair saturation would be suitable for heavy-ion radiotherapy. PMID- 27380804 TI - Changes in the distribution and function of leukocytes after whole-body iron ion irradiation. AB - High-energy particle radiation could have a considerable impact on health during space missions. This study evaluated C57BL/6 mice on Day 40 after total-body 56Fe26+ irradiation at 0, 1, 2 and 3 gray (Gy). Radiation consistently increased thymus mass (one-way ANOVA: P < 0.005); spleen, liver and lung masses were similar among all groups. In the blood, there was no radiation effect on the white blood cell (WBC) count or major leukocyte types. However, the red blood cell count, hemoglobin, hematocrit and the CD8+ T cytotoxic (Tc) cell count and percentage all decreased, while both the CD4:CD8 (Th:Tc) cell ratio and spontaneous blastogenesis increased, in one or more irradiated groups compared with unirradiated controls (P < 0.05 vs 0 Gy). In contrast, splenic WBC, lymphocyte, B cell and T helper (Th) counts, %B cells and the CD4:CD8 ratio were all significantly elevated, while Tc percentages decreased, in one or more of the irradiated groups compared with controls (P < 0.05 vs 0 Gy). Although there were trends for minor, radiation-induced increases in %CD11b+ granulocytes in the spleen, cells double-labeled with adhesion markers (CD11b+CD54+, CD11b+CD62E+) were normal. Splenocyte spontaneous blastogenesis and that induced by mitogens (PHA, ConA, LPS) was equivalent to normal. In bone marrow, the percentage of cells expressing stem cell markers, Sca-1 and CD34/Sca-1, were low in one or more of the irradiated groups (P < 0.05 vs 0 Gy). Collectively, the data indicate that significant immunological abnormalities still exist more than a month after 56Fe irradiation and that there are differences dependent upon body compartment. PMID- 27380805 TI - A stochastic multicellular model identifies biological watermarks from disorders in self-organized patterns of phyllotaxis. AB - Exploration of developmental mechanisms classically relies on analysis of pattern regularities. Whether disorders induced by biological noise may carry information on building principles of developmental systems is an important debated question. Here, we addressed theoretically this question using phyllotaxis, the geometric arrangement of plant aerial organs, as a model system. Phyllotaxis arises from reiterative organogenesis driven by lateral inhibitions at the shoot apex. Motivated by recurrent observations of disorders in phyllotaxis patterns, we revisited in depth the classical deterministic view of phyllotaxis. We developed a stochastic model of primordia initiation at the shoot apex, integrating locality and stochasticity in the patterning system. This stochastic model recapitulates phyllotactic patterns, both regular and irregular, and makes quantitative predictions on the nature of disorders arising from noise. We further show that disorders in phyllotaxis instruct us on the parameters governing phyllotaxis dynamics, thus that disorders can reveal biological watermarks of developmental systems. PMID- 27380807 TI - Incidence rates for lung and bronchus cancer of Japanese in Japan and in the United States from the Cancer Incidence in Five Continents. PMID- 27380806 TI - A retrospective study of treatment and prophylaxis of ifosfamide-induced hemorrhagic cystitis in pediatric and adolescent and young adult (AYA) patients with solid tumors. AB - OBJECTIVE: Ifosfamide (IFO) is considered an essential drug for the treatment of pediatric, adolescent and young adult patients with solid tumors. Hemorrhagic cystitis (HC) is one of the dose-limiting toxicity of IFO. However, there are insufficient evidence for risk factor and supportive care of IFO-induced HC. METHODS: In this retrospective study, patients (<30-year-old) with malignant solid tumors who had been treated with IFO-based chemotherapy, were categorized according to the presence or absence of HC, and were analyzed possible risk factors for IFO-induced HC. In our institution, continuous hydration to increase urine output and intravenous 2-mercaptethane sulfonate (mesna) are used for prophylaxis of IFO-induced HC. Increased hydration and dosage of mesna are administered to patients who develop IFO-induced HC; they also receive 24-h continuous infusion of mesna in subsequent treatment cycles. RESULTS: Nine treatment regimens were used in the 70 study patients. The range of daily IFO dosage was 1.2-3.0 g/m(2). HC occurred in 14/425 IFO-based chemotherapy cycles (3.3%). The daily IFO dosages (mean +/- SD) in patients with or without HC were 2.23 +/- 0.58 g/m(2) and 1.85 +/- 0.50 g/m(2), respectively (P = 0.006). Only one of the nine patients who developed IFO-induced HC had experienced this complication in a subsequent cycle of treatment. CONCLUSION: The incidence of IFO induced HC may be associated with the dosage of IFO. When administering IFO higher than 2.0 g/m(2)/day, the volume of hydration, dosage of mesna and duration of mesna infusion should be increased to prevent HC. PMID- 27380808 TI - Nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy mimicking rapid-onset Guillain-Barre syndrome: a case report. AB - Nivolumab, an anti-programmed death-1-specific monoclonal antibody, has demonstrated a durable response and effect on overall survival and has become one of the standard treatments for patients with advanced melanoma. Reported herein is a case of nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy, in which an 85-year-old woman with stage IV melanoma developed grade 1 paresthesia 2 weeks after the initial dose of nivolumab was administered. With continued treatment, the neurological deficiency deteriorated rapidly, mimicking Guillain-Barre syndrome, causing such a dramatic decrease in her activities of daily living that she could no longer function in daily life. Thus, nivolumab treatment was discontinued. A course of intravenous immunoglobulin infusion yielded a dramatic clinical improvement; in particular, improved motor control was observed within a few days. Her initial presentation was suggestive of acute inflammatory demyelinating polyradiculoneuropathy, a subtype of Guillain-Barre syndrome; however, the good response to steroids and exacerbation 8 weeks after the onset were suggestive of chronic inflammatory demyelinating polyradiculoneuropathy induced by nivolumab. This is the first case of Guillain-Barre syndrome-like autoimmune polyradiculoneuropathy induced by programmed death-1/programmed death-ligand 1 inhibitors. Although neurological adverse events related to nivolumab are rare, they can become severe, requiring early diagnosis and intervention. Intravenous immunoglobulin may be considered as an effective initial treatment for patients who develop acute autoimmune nervous system disorders due to nivolumab. PMID- 27380809 TI - Safety and discomfort during bronchoscopy performed under sedation with fentanyl and midazolam: a prospective study. AB - OBJECTIVE: Although sedation with fentanyl and midazolam during bronchoscopic examination is widely accepted in the USA and Europe, it is not routine practice in Japan. The objective of the present study was to evaluate sedation with fentanyl and midazolam during bronchoscopy. METHODS: Thirty-seven patients were enrolled prospectively between November 2014 and July 2015 at Okayama University Hospital. Fentanyl (20 MUg) was administered to the patients just before the examination, and fentanyl (10 MUg) and midazolam (1 mg) were added as needed during the procedure. A questionnaire was administered 2 hours after the examination. In the questionnaire, patient satisfaction was scored using a visual analog scale as follows: great (1 point), good (2 points), normal (3 points), uncomfortable (4 points) and very uncomfortable (5 points). An additional question ('Do you remember the bronchoscopic examination?') was also used. Predefined matters for investigation (e.g. blood pressure, heart rate, oxygen saturation and complications) were recorded. RESULTS: The enrolled patients included 13 males and 24 females; the median age was 67 (range: 31-87) years. The patients received a median dose of fentanyl of 45.4 MUg (range: 30-100 MUg) and midazolam of 2.56 mg (range: 1-10 mg). Twenty-six patients (70.2%) agreed to undergo a second bronchoscopic examination, and the average levels of discomfort and re-examination were 2.02 points for each. Only 37.8% of the patients remembered the bronchoscopic examination. No severe complications were reported. CONCLUSIONS: Sedation with fentanyl and midazolam during bronchoscopic examination should be recommended for use in Japan. PMID- 27380810 TI - Chemoradiotherapy for esophageal squamous cell cancer. AB - Chemoradiotherapy has been clinically indicated for patients with resectable esophageal squamous cell carcinoma who refuse surgical resection and in locally advanced unresectable esophageal squamous cell carcinoma patients. Concurrent chemoradiotherapy prolongs survival than radiation therapy alone when given as definitive treatment. Therefore, chemoradiotherapy is recognized as the standard non-invasive treatment for patients with localized esophageal cancer who opt for non-surgical treatment. JCOG9906 showed promising outcomes for stage II/III ESCC patients. But there are some problems about chemoradiotherapy for esophageal squamous cell carcinoma. Late toxicities are sometimes lethal for patients who achieved complete response even after years. Salvage treatment for residual or recurrent disease is unestablished. Modified Radiation Therapy Oncology Group regimen at the dose of 50.4 Gy reduced late toxicities without reducing efficacy. Optimal timings and procedure of salvage surgery and endoscopic therapy is evaluated in JCOG0909. Strategy including salvage therapy after chemoradiotherapy should be considered at the time of starting the treatment. Targeted therapy has not shown adding effect for chemoradiotherapy for esophageal squamous cell carcinoma yet. New agents, such as immune checkpoint inhibitors, are expected to show synergistic effect with chemoradiotherapy for esophageal squamous cell carcinoma. Further investigation is needed. PMID- 27380811 TI - Serum microRNA expression profile as a diagnostic panel for gastric cancer. AB - PURPOSE: Previously, we identified six miRNAs that are differentially expressed in colorectal cancer compared with healthy controls. Here, we tested them in gastric cancer GC. METHODS: We performed quantitative RT-PCR on serum samples from 92 patients with gastric cancer and 89 controls for the six miRNAs, and analyzed their risk scores to evaluate the diagnostic value of the serum miRNA profiling system. RESULTS: After a two-phase selection and validation process, five miRNAs were found to significantly differ in expression between gastric cancer samples and control samples, including miR-21, miR-31, miR-92a, miR-181b, and miR-203. Risk score analysis showed that this miRNA panel could distinguish gastric cancer cases from controls with high sensitivity and specificity. Under receiver operating characteristic curves, areas under the curve for tumor identification were 0.933 (95% confidence interval [CI]: 0.86-1.007) for the training set and 0.919 (95% CI: 0.863-0.975) for the validation set-markedly higher than those of carcinoembryonic antigen (0.624) and carbohydrate antigen 19 9 (0.603). CONCLUSIONS: The signature of these five miRNAs is a novel and noninvasive biomarker for gastric cancer, and could facilitate and simplify its diagnosis. PMID- 27380812 TI - Developmental dynamics of occipital and cervical somites. AB - Development of somites leading to somite compartments, sclerotome, dermomyotome and myotome, has been intensely investigated. Most knowledge on somite development, including the commonly used somite maturation stages, is based on data from somites at thoracic and lumbar levels. Potential regional differences in somite maturation dynamics have been indicated by a number of studies, but have not yet been comprehensively examined. Here, we present an overview on the developmental dynamics of somites at occipital and cervical levels in the chicken embryo. We show that in these regions, the onset of sclerotomal and myotomal compartment formation is later than at thoracolumbar levels, and is initiated simultaneously in multiple somites, which is in contrast to the serial cranial- to- caudal progression of somite maturation in the trunk. Our data suggest a variant spatiotemporal regulation of somite development in occipitocervical somites. PMID- 27380813 TI - From Reproductive Rights to Responsibilization: Fashioning Liberal Subjects in Mexico City's New Public Sector Abortion Program. AB - Building on medical anthropology literature that analyzes doctor-patient interactions as a charged site for the production of political subjectivities, I demonstrate how a central feature of Mexico City's new public sector abortion program involves "responsibilization." In accordance with entrenched Ministry of Health objectives, providers transmit a suite of values about personal responsibility and self-regulation through the use of birth control, hinging abortion rights to responsible reproductive subjectivity. Based on 18 months of ethnographic research across program clinics, including 75 interviews with patients and providers, I show how interrupcion legal del embarazo protocols fashion "responsibilized" liberal subjects. I argue that the recent granting of abortion rights in Mexico City-ostensibly a new moment for the construction of women's citizenship-instead reflects and extends long-standing state agendas of "reproductive governance." My analysis of reproductive rights as the newest framing of ongoing population policies in Mexico adds to a critical anthropology of human rights and of liberal projects of governance. PMID- 27380814 TI - Regioselective Synthesis of C-3-Functionalized Quinolines via Hetero-Diels-Alder Cycloaddition of Azadienes with Terminal Alkynes. AB - A highly efficient metal and protection-free approach for the regioselective synthesis of C-3-functionalized quinolines from azadienes (in situ generated from 2-aminobenzyl alcohol) and terminal alkynes through [4 + 2] cycloaddition has been developed. An unprecedented reaction of 2-aminobenzyl alcohol with 1,3- and 1,4-diethynylbenzene provided the C-3 tolylquinolines via [4 + 2] HDA and oxidative decarboxylation. The -NH2 group directed mechanistic approach was well supported by the control experiments and deuterium-labeling studies and by isolating the azadiene intermediate. The reactivity and selectivity of unprotected azadiene in metal-free base-assisted hetero-Diels-Alder reaction is exploited to quickly assemble an important class of C-3-functionalized quinolines, which are difficult to access. PMID- 27380815 TI - Designing a multicolor long range nanoscopic ruler for the imaging of heterogeneous tumor cells. AB - Tumor heterogeneity is one of the biggest challenges in cancer treatment and diagnosis. A multicolor optical ruler is essential to address the heterogeneous tumor cell complexity. Driven by this need, the current article reports the design of a multicolor long range nanoscopic ruler for screening tumor heterogeneity by accurately identifying epithelial cells and cancer stem cells (CSCs) simultaneously. A nanoscopic surface energy transfer (NSET) ruler has been developed using blue fluorescence polymer dots (PDs) and red fluorescence gold cluster dots (GCDs) as multicolor fluorescence donor and plasmonic gold nanoparticle (GNP) acts as an excellent acceptor. Reported experimental results demonstrated that the multicolor nanoscopic ruler's working window is above 35 nm distances, which is more than three times farther than that of Forster resonance energy transfer (FRET) distance limit. Theoretical modeling using Forster dipole dipole coupling and dipole to nanoparticle surface energy transfer have been used to discuss the possible mechanism for multicolor nanoscopic ruler's long-range capability. Using RNA aptamers that are specific for the target cancer cells, experimental data demonstrate that the nanoscopic ruler can be used for screening epithelial and CSCs simultaneously from a whole blood sample with a detection capability of 10 cells per mL. Experimental data show that the nanoscopic ruler can distinguish targeted cells from non-targeted cells. PMID- 27380817 TI - Programmable Bio-nanochip Platform: A Point-of-Care Biosensor System with the Capacity To Learn. AB - The combination of point-of-care (POC) medical microdevices and machine learning has the potential transform the practice of medicine. In this area, scalable lab on-a-chip (LOC) devices have many advantages over standard laboratory methods, including faster analysis, reduced cost, lower power consumption, and higher levels of integration and automation. Despite significant advances in LOC technologies over the years, several remaining obstacles are preventing clinical implementation and market penetration of these novel medical microdevices. Similarly, while machine learning has seen explosive growth in recent years and promises to shift the practice of medicine toward data-intensive and evidence based decision making, its uptake has been hindered due to the lack of integration between clinical measurements and disease determinations. In this Account, we describe recent developments in the programmable bio-nanochip (p-BNC) system, a biosensor platform with the capacity for learning. The p-BNC is a "platform to digitize biology" in which small quantities of patient sample generate immunofluorescent signal on agarose bead sensors that is optically extracted and converted to antigen concentrations. The platform comprises disposable microfluidic cartridges, a portable analyzer, automated data analysis software, and intuitive mobile health interfaces. The single-use cartridges are fully integrated, self-contained microfluidic devices containing aqueous buffers conveniently embedded for POC use. A novel fluid delivery method was developed to provide accurate and repeatable flow rates via actuation of the cartridge's blister packs. A portable analyzer instrument was designed to integrate fluid delivery, optical detection, image analysis, and user interface, representing a universal system for acquiring, processing, and managing clinical data while overcoming many of the challenges facing the widespread clinical adoption of LOC technologies. We demonstrate the p-BNC's flexibility through the completion of multiplex assays within the single-use disposable cartridges for three clinical applications: prostate cancer, ovarian cancer, and acute myocardial infarction. Toward the goal of creating "sensors that learn", we have developed and describe here the Cardiac ScoreCard, a clinical decision support system for a spectrum of cardiovascular disease. The Cardiac ScoreCard approach comprises a comprehensive biomarker panel and risk factor information in a predictive model capable of assessing early risk and late-stage disease progression for heart attack and heart failure patients. These marker-driven tests have the potential to radically reduce costs, decrease wait times, and introduce new options for patients needing regular health monitoring. Further, these efforts demonstrate the clinical utility of fusing data from information-rich biomarkers and the Internet of Things (IoT) using predictive analytics to generate single-index assessments for wellness/illness status. By promoting disease prevention and personalized wellness management, tools of this nature have the potential to improve health care exponentially. PMID- 27380819 TI - Preprocedural but not periprocedural high-sensitive Troponin T levels predict outcome in patients undergoing transcatheter aortic valve implantation. AB - AIM: Risk assessment of patients undergoing transcatheter aortic valve implantation (TAVI) remains difficult. Biomarkers have been shown to provide potential prognostic information. Here, we aimed to analyze whether the biomarker high-sensitivity Troponin T (hsTNT) could be used to improve risk stratification. METHOD: We prospectively enrolled 267 patients undergoing TAVI. Biomarkers (hsTNT and NTproBNP) were measured 1 day before, and 3 and 7 days postprocedure. All possible prognostic factors upon survival time were analyzed by Cox regression analysis. RESULTS: A total of 259 patients (mean age 82+/-6.1 years) were available for complete follow-up. The median Logistic EuroSCORE (Log ES) and Log ES II were 21.16% (Q1=13.92; Q3=34.27) and 6.42% (Q1=3.89; Q3=11.07), respectively. Median follow-up was 290 (Q1=88; Q3=529) days. A total of 71 deaths occurred during follow-up, and the 30-day mortality was 5.8%. Median baseline hsTNT was 27.4 pg/mL (Q1=16.2; Q3=46 pg/mL). From all potential mortality associated factors, only preprocedural hsTNT level (P=.001), elevated Log ES (P=.03) as well as acute kidney injury (P<.001) and chronic obstructive pulmonary disease (COPD) (P=.039) emerged as independent prognostic parameters for adverse outcome. We also tested whether the Valve Academic Research Consortium-2 (VARC II) cutoff for myocardial damage (hsTNT peak value exceeding 15* the upper reference limit + at least 50% increase) was of prognostic relevance. At 72-hours post-TAVI, 36.2% of the patients matched these VARC-II criteria of myocardial damage. However, these patients did not display a difference in survival compared to patients without significant myocardial injury. CONCLUSION: Elevated preprocedural hsTNT represents an independent risk predictor of all-cause death while periprocedural hsTNT elevation failed to show prognostic relevance. PMID- 27380820 TI - MOF catalysis of Fe(II)-to-Fe(III) reaction for an ultrafast and one-step generation of the Fe2O3@MOF composite and uranium(vi) reduction by iron(ii) under ambient conditions. AB - Herein, we demonstrate that Zn-MOF-74 enables the ultrafast and one-step generation of the Fe2O3@MOF composite once Zn-MOF-74 contacts with FeSO4 solution. This unique reaction can be further applied in catalysis of U(vi) reduction by Fe(ii) under ambient conditions. The results provide a highly renovated strategy for U(vi) reduction by Fe(ii) just under ambient conditions, which completely subvert all established methods about U(vi) reduction by Fe(ii) in which O2- and CO2-free conditions are absolutely required. PMID- 27380821 TI - Genetic analysis of neuraminidase gene of influenza A(H1N1)pdm09 virus circulating in Southwest India from 2009 to 2012. AB - Genetic analysis of neuraminidase gene sequences in 23 archived isolates of influenza A(H1N1)pdm09 virus, isolated during the 2009-2012 influenza seasons, was carried out to determine the genetic variability. Amino acid substitutions were observed at the rates of 0.3-0.7% per year. The catalytic site consisting of 8 functional and 11 framework residues were found conserved in 20 isolates and mutated in three (E228G, E278G, and N295T) isolates. To the best of our knowledge the three catalytic site mutants observed in our study have not been reported elsewhere to date. Similarly, mutations in the antigenic sites (K217E, K254E, V267A, and D451E except I263V) are discussed for the first time through this article. The effect of these mutations on drug and antibody binding were analyzed using biochemical and structural studies. Detailed studies on the neuraminidase gene are sparse and our study may serve as an appropriate platform to gain insights about the evolution of influenza virus, thereby facilitating drugs/vaccines design and development. J. Med. Virol. 89:202-212, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27380822 TI - Dynamics of ultrathin V-oxide layers on Rh(111) in catalytic oxidation of ammonia and CO. AB - Catalytic oxidation of ammonia and CO has been studied in the 10(-4) mbar range using a catalyst prepared by depositing ultra-thin vanadium oxide layers on Rh(111) (thetaV ~ 0.2 MLE). Using photoemission electron microscopy (PEEM) as a spatially resolving method, we observe that upon heating in an atmosphere of NH3 and O2 the spatial homogeneity of the VOx layer is removed at 800 K and a pattern consisting of macroscopic stripes develops; at elevated temperatures this pattern transforms into a pattern of circular VOx islands. Under reaction conditions the neighboring VOx islands become attracted by each other and coalesce. Similar processes of pattern formation and island coalescence are observed in catalytic CO oxidation. Reoxidation of the reduced VOx catalyst proceeds via surface diffusion of oxygen adsorbed onto Rh(111). A pattern consisting of macroscopic circular VOx islands can also be obtained by heating a Rh(111)/VOx catalyst in pure O2. PMID- 27380824 TI - Preferred practice location at medical school commencement strongly determines graduates' rural preferences and work locations. AB - OBJECTIVE: To identify factors influencing whether Australian medical graduates prefer to, or actually, work rurally. DESIGN: Secondary analysis of longitudinal data from Medical Schools Outcomes Database (MSOD) using univariate and multivariate logistic regression. SETTING: Twenty Australian medical schools. PARTICIPANTS: Australian or New Zealand citizens and Australian permanent residents who completed MSOD questionnaires between 2006 and 2013. MAIN OUTCOME MEASURES: Preferred and actual work locations 1 (PGY1) and 3 (PGY3) years postgraduation. RESULTS: Of 20 784 participants, 4028 completed a PGY1 or PGY3 questionnaire. Self-reported preference for rural practice location at medical school commencement was the most consistent independent predictor of whether a graduate would have a rural location preference at PGY1 (odds ratio (OR) 6.07, 95% confidence interval (CI) 4.91-7.51) and PGY3 (OR 7.95, 95% CI 4.93-12.84), and work rurally during PGY1 (OR 1.38, 95% CI 1.01-1.88) and PGY3 (OR 1.86, 95% CI 1.30-2.64). The effect of preferred practice location at medical school commencement is independent of, and enhances the effect of, rural background. Graduates of graduate-entry programs or with dependent children were less likely to have worked rurally during PGY1 and PGY3 respectively. CONCLUSION: The most consistent factor associated with rural preferences and work location was students' preferred location of practice at medical school commencement; this association is independent of, and enhances the effect of, rural background. Better understanding of what determines rural preference at medical school commencement and its influence on rural workplace outcomes beyond PGY3 is required to inform Australian medical school selection policies and rural health curricula. PMID- 27380825 TI - Efficient Secretion of the beta-Galactosidase Bgal1-3 via both Tat-Dependent and Tat-Independent Pathways in Bacillus subtilis. AB - In this study, the twin-arginine (Tat) signal peptide PhoD was used to direct the secretion of the beta-galactosidase Bgal1-3 into the growth medium of an engineered strain of Bacillus subtilis 168. After 24 h of cultivation, the extracellular activity reached 1.15 U/mL, representing 78% of the total activity. Bgal1-3 was exported via both Tat-dependent and Tat-independent pathways. To improve the secretion amounts, two more copies of the target gene were inserted into the designated loci on the chromosome, further improving the extracellular enzymatic activity to 2.15 U/mL. The engineered strain with three copies of bgal1 3 was genetically stable after 150 generations. To the best of our knowledge, this is the first report on the functional secretion of a heterologous protein via both Tat-dependent and Tat-independent pathways mediated by a Tat signal peptide in B. subtilis. Furthermore, this study provides us with a markerless engineered strain for the production of beta-galactosidase. PMID- 27380826 TI - Less thrombolysis in posterior circulation infarction-a necessary evil? AB - OBJECTIVES: Patients with posterior circulation infarction (PCI) have more subtle symptoms than anterior circulation infarction (ACI) and could come too late for acute intervention. This study aimed to describe the clinical presentation, management, and outcome of PCI in the NORSTROKE registry. METHODS: All patients with PCI admitted to the Department of Neurology at Haukeland University Hospital and registered in the NORSTROKE database 2006-2013 were included (n=686). Patients with ACI (n=1758) were used for comparison. RESULTS: Patients with PCI were younger (68.2 vs 71.8, P<.001), had longer median time from symptom onset to admission (3.8 hours vs 2.2 hours, P<.001), and were less likely to arrive at hospital within 4.5 hours from symptom onset (56.2% vs 72.5%, P<.001, ictus known). Patients with PCI scored lower on baseline National Institute of Health Stroke Scale (NIHSS) total score (3.2 vs 6.3, P<.001), and lower or equally on all items of NIHSS, except for ataxia in two limbs. Patients with PCI were less likely to receive i.v. thrombolytic treatment (9.9% vs 21.5%, OR 0.66, CI 0.47 0.94). On day 7, patients with PCI scored lower on NIHSS (2.8 vs 4.9, P<.001), modified Rankin Scale (2.0 vs 2.3, P<.001), and higher on Barthel Index (84.5 vs 76.0, P<.001). CONCLUSIONS: Our study is, to our knowledge, the largest series reporting comprehensively on PCI verified by diffusion-weighted imaging. PCI patients are younger than ACI and have better outcome. PCI and ACI are equally investigated in the acute setting, but thrombolysis rates remain 50% lower in PCI. PMID- 27380827 TI - Visualizing Dealumination of a Single Zeolite Domain in a Real-Life Catalytic Cracking Particle. AB - Fluid catalytic cracking (FCC) catalysts play a central role in the chemical conversion of crude oil fractions. Using scanning transmission X-ray microscopy (STXM) we investigate the chemistry of one fresh and two industrially deactivated (ECAT) FCC catalysts at the single zeolite domain level. Spectro-microscopic data at the Fe L3 , La M5 , and Al K X-ray absorption edges reveal differing levels of deposited Fe on the ECAT catalysts corresponding with an overall loss in tetrahedral Al within the zeolite domains. Using La as a localization marker, we have developed a novel methodology to map the changing Al distribution of single zeolite domains within real-life FCC catalysts. It was found that significant changes in the zeolite domain size distributions as well as the loss of Al from the zeolite framework occur. Furthermore, inter- and intraparticle heterogeneities in the dealumination process were observed, revealing the complex interplay between metal-mediated pore accessibility loss and zeolite dealumination. PMID- 27380828 TI - Influence of olive ripening degree and crusher typology on chemical and sensory characteristics of Correggiolo virgin olive oil. AB - BACKGROUND: In this study, two types of crusher, hammer and blade, were used to produce olive oils from cv. Correggiolo olives at four stages of ripeness, to analyse the effect of these two factors on oil quality indices (free acidity, peroxide value, UV absorption), on phenolic compounds content and sensory profiles. Differences in chemical and sensory data were analysed by two-way ANOVA. RESULTS: Ripeness exerted a stronger influence than the crushing equipment on quality indices, phenolic content and sensory evaluation; moreover the statistical significance of interaction between the factors considered suggests that they are intertwined. Differences in the texture of olive pastes obtained by squashing and crushing were clearly evident at the first stage of ripeness via observation with a scanning electron microscope. The stronger mechanical action of the hammer crusher also produced smaller pit fragments compared to the blade crusher, as shown by particle size analysis of the kernels fragments. CONCLUSION: Knowledge about the interaction between ripening and crushing will allow olive oil producers to pursue a product of the quality most suitable for a particular type of consumer. For example, bitterness and pungency, characters recently connected with health effects because sensory markers of extra virgin olive oil (EVOO) polyphenols, do not have a great sensory appeal for most consumers; however, there is a niche of gourmet estimators interested in these peculiar flavours and ready to pay a premium price for them. The producer will be able to customise the EVOO by modulating its chemical and sensory characteristics, especially the phenolic fraction, thus addressing the needs of consumers with different tastes. (c) 2016 Society of Chemical Industry. PMID- 27380829 TI - Photochemistry of Transition Metal Hydrides. AB - Photochemical reactivity associated with metal-hydrogen bonds is widespread among metal hydride complexes and has played a critical part in opening up C-H bond activation. It has been exploited to design different types of photocatalytic reactions and to obtain NMR spectra of dilute solutions with a single pulse of an NMR spectrometer. Because photolysis can be performed on fast time scales and at low temperature, metal-hydride photochemistry has enabled determination of the molecular structure and rates of reaction of highly reactive intermediates. We identify five characteristic photoprocesses of metal monohydride complexes associated with the M-H bond, of which the most widespread are M-H homolysis and R-H reductive elimination. For metal dihydride complexes, the dominant photoprocess is reductive elimination of H2. Dihydrogen complexes typically lose H2 photochemically. The majority of photochemical reactions are likely to be dissociative, but hydride complexes may be designed with equilibrated excited states that undergo different photochemical reactions, including proton transfer or hydride transfer. The photochemical mechanisms of a few reactions have been analyzed by computational methods, including quantum dynamics. A section on specialist methods (time-resolved spectroscopy, matrix isolation, NMR, and computational methods) and a survey of transition metal hydride photochemistry organized by transition metal group complete the Review. PMID- 27380830 TI - A mixed-methods study of health worker migration from Jamaica. AB - BACKGROUND: This study sought to better understand the drivers of migration, its consequences, and the various strategies countries have employed to mitigate its negative impacts. The study was conducted in four countries-Jamaica, India, the Philippines, and South Africa-that have historically been 'sources' of health workers migrating to other countries. The aim of this paper is to present the findings from the Jamaica portion of the study. METHODS: Data were collected using surveys of Jamaica's generalist and specialist physicians, nurses, midwives, and dental auxiliaries, as well as structured interviews with key informants representing government ministries, professional associations, regional health authorities, healthcare facilities, and educational institutions. Quantitative data were analyzed using descriptive statistics and regression models. Qualitative data were analyzed thematically. Multiple stakeholder engagement workshops were held across Jamaica to share and validate the study findings and discuss implications for the country. RESULTS: Migration of health workers from Jamaica continues to be prevalent. Its causes are numerous, long standing, and systemic, and are largely based around differences in living and working conditions between Jamaica and 'destination' countries. There is minimal formal tracking of health worker migration from Jamaica, making scientific analysis of its consequences difficult. Although there is evidence of numerous national and international efforts to manage and mitigate the negative impacts of migration, there is little evidence of the implementation or effectiveness of such efforts. Potential additional strategies for better managing the migration of Jamaica's health workers include the use of information systems to formally monitor migration, updating the national cadre system for employment of health personnel, ensuring existing personnel management policies, such as bonding, are both clearly understood and equitably enforced, and providing greater formal and informal recognition of health personnel. CONCLUSION: Although historically common, migration of Jamaica's health workers is poorly monitored and understood. Improved management of the migration of Jamaica's health workers requires collaboration from stakeholders across multiple sectors. Indeed, participating stakeholders identified a wide range of potential strategies to better manage migration of Jamaica's health workers, the implementation and testing of which will have potential benefits to Jamaica as well as other 'source' countries. PMID- 27380831 TI - Whole genome sequencing of a dizygotic twin suggests a role for the serotonin receptor HTR7 in autism spectrum disorder. AB - Whole genome sequencing of a severely affected dizygotic twin with an autism spectrum disorder and intellectual disability revealed a compound heterozygous mutation in the HTR7 gene as the only variation not detected in control databases. Each parent carries one allele of the mutation, which is not present in an unaffected stepsister. The HTR7 gene encodes the 5-HT7 serotonin receptor that is involved in brain development, synaptic transmission, and plasticity. The paternally inherited p.W60C variant is situated at an evolutionary conserved nucleotide and predicted damaging by Polyphen2. A mutation akin to the maternally inherited pV286I mutation has been reported to significantly affect the binding characteristics of the receptor. Therefore, the observed sequence alterations provide a first suggestive link between a genetic abnormality in the HTR7 gene and a neurodevelopmental disorder. (c) 2016 Wiley Periodicals, Inc. PMID- 27380832 TI - Aerosol-Assisted Synthesis of Porous TiNx Oy @C Nanocomposites. AB - Porous TiNx Oy -based particles were synthesized by an aerosol spray process. At first, the starting sol solution containing the metal precursor and the nitrogen source is sprayed to form an aerosol that is subsequently pyrolysed at different temperatures. The obtained dried particles are an amorphous coordination "polymer" rich in carbon and nitrogen. These "glassy" particles are finally thermally treated at 800 degrees C, promoting the crystallization of the particles and the release of a major part of the carbon. As the particles keep their original shape, carbon loss and density increase during the crystallization step and lead to the development of an accessible pore structure. The process was analyzed and extended to the synthesis of other metal nitrides, such as VN and W2 N, thereby showing its general validity for the production of functional nanocrystalline nitride ceramics with high porosity still occupying a relatively small volume, and otherwise not easily accessible. PMID- 27380833 TI - Hepatitis E Virus: A Cross-Sectional Serological and Virological Study in Pigs and Humans at Zoonotic Risk within a High-Density Pig Farming Area. AB - An increase in autochthonous hepatitis E virus (HEV) infections has been recorded in Italy suspected to be zoonotically transmitted from pigs; this study was carried out to determinate the seroprevalence and risk factors associated with hepatitis HEV exposition, both in swine and humans working in pig farms, located within a high-density pig farming area in Piedmont region, north-western Italy. The presence of viral RNA in human and swine samples was also evaluated, and phylogenetic analysis was performed on HEV-positive samples. Forty-two swine farms were sampled; 142 workers were enrolled in the study and classified into two groups: (i) 69 workers with occupational contact with swine (including veterinarians and farmers) recruited in the 42 sampled farms; (ii) 73 without occupational contact with swine. Forty-one of 42 (97%) swine farms resulted positive to enzyme-linked immunosorbent assay test for HEV antibodies (Abs). Overall seroprevalence in swine was 50% (441/879), with seropositivity rate higher in sows (333/469, 71%). HEV RNA in stool samples was detected in animals from 13 of 42 tested farms (31%), and a higher positivity resulted in weaners (40/246, 16.3%). Phylogenetic analysis classified all HEV isolates within genotype 3 (subtypes 3f, 3e, 3c). All humans were negative for HEV viral genome in blood. Five of 142 sera were positive for IgG anti-HEV with an overall prevalence of 3.52% with no statistically significant differences in prevalence rates between workers at zoonotic risk and the control group (5.7% versus 1.3%). In contrast, a significant difference (OR 10.1) was observed within the subgroup including subjects exposed for short periods (veterinarians) compared with those who worked for long periods (farmers) suggesting a correlation between the time of exposure and the likelihood of HEV infection. Reporting HEV infection is not mandatory in Italy, but a constant epidemiological surveillance should be ensured to clarify the epidemiology of this disease. PMID- 27380834 TI - Development and validation of the brief esophageal dysphagia questionnaire. AB - BACKGROUND: Esophageal dysphagia is common in gastroenterology practice and has multiple etiologies. A complication for some patients with dysphagia is food impaction. A valid and reliable questionnaire to rapidly evaluate esophageal dysphagia and impaction symptoms can aid the gastroenterologist in gathering information to inform treatment approach and further evaluation, including endoscopy. METHODS: 1638 patients participated over two study phases. 744 participants completed the Brief Esophageal Dysphagia Questionnaire (BEDQ) for phase 1; 869 completed the BEDQ, Visceral Sensitivity Index, Gastroesophageal Reflux Disease Questionnaire, and Hospital Anxiety and Depression Scale for phase 2. Demographic and clinical data were obtained via the electronic medical record. The BEDQ was evaluated for internal consistency, split-half reliability, ceiling and floor effects, and construct validity. KEY RESULTS: The BEDQ demonstrated excellent internal consistency, reliability, and construct validity. The symptom frequency and severity scales scored above the standard acceptable cutoffs for reliability while the impaction subscale yielded poor internal consistency and split-half reliability; thus the impaction items were deemed qualifiers only and removed from the total score. No significant ceiling or floor effects were found with the exception of 1 item, and inter-item correlations fell within accepted ranges. Construct validity was supported by moderate yet significant correlations with other measures. The predictive ability of the BEDQ was small but significant. CONCLUSIONS & INFERENCES: The BEDQ represents a rapid, reliable, and valid assessment tool for esophageal dysphagia with food impaction for clinical practice that differentiates between patients with major motor dysfunction and mechanical obstruction. PMID- 27380835 TI - An improved model for provision of rural community-based health rehabilitation services in Vhembe District, Limpopo Province of South Africa. AB - BACKGROUND: In 1991, Riakona Community Rehabilitation Programme initiated community-based rehabilitation (CBR) in the Vhembe District of Limpopo Province. Subsequently, the South African government adopted the programme. AIM: The aim of the study was to suggest an improvement in the model of providing CBR services. SETTING: The study was conducted in six rehabilitation centres located in hospitals in the Vhembe District in Limpopo Province of South Africa. METHOD: A mixed-mode research design with qualitative and quantitative elements was used to conduct the study. Content analysis, the chi-square test for Goodness of Fit and the Kruskal-Wallis and Mann-Whitney non-parametric tests were conducted. RESULTS: The key determinants of client satisfaction with the services that the community rehabilitation workers rendered included provision of assistive devices and the adoption of a holistic approach to their work. Overall, satisfaction per domain for each one of the five domains of satisfaction scored less than 90%. More than 80% of clients were satisfied with empathy (83%) and assurance (80%) domains. Tangibles, reliability and responsiveness domains had scores of 78%, 72% and 67%, respectively. These results, together with the reasoning map of conceptual framework description, were used as the building blocks of the CBR model. CONCLUSION: The improved CBR model is useful for putting the programme into practice. This is particularly so for the CBR managers in the districts of the Limpopo Province. PMID- 27380836 TI - Awareness of prevention of teenage pregnancy amongst secondary school learners in Makhado municipality. AB - BACKGROUND: Sexuality plays a very significant role in the lives of both boys and girls. It is, therefore, considered important for schools to recognise and accept sexuality as part of the development process of the child. Professor Kader Asmal (previous South African Minister of Education) suggested that the earlier the school begins to teach learners about sexuality, the better because they can be easily misled by their peers if proper guidance regarding their sexuality is not given. AIM: The current study was conducted to assess the awareness of teenagers on the prevention of teenage pregnancy (TP) in six secondary school learners situated in the Soutpansberg-West circuit, Makhado Municipality in Limpopo province. SETTING: The study was conducted at six secondary schools situated in the Soutpansberg-West circuit, Makhado Municipality in Limpopo province in 2014. METHODOLOGY: A quantitative descriptive survey study was conducted where data were collected, using self-administered questionnaires, from 381 systematically sampled participants from six secondary schools situated in the Soutpansberg-West circuit, Makhado Municipality in Limpopo province. Data were analysed descriptively using the Statistical Package for the Social Sciences (SPSS) software, version 22.0. Necessary approval procedures and ethical clearance were obtained prior to data collection. RESULTS: Ninety-four percent of participants agreed that TP can be prevented through abstaining from sex, whilst 65% of participants agreed that TP could be prevented by using contraceptives such as pills and injections. Eighty-three percent of participants agreed that T Pcould be prevented through the use of condoms. Seventy-four percent participants disagreed that bathing after sex prevents teenage pregnancies. Furthermore, 28% participants agreed that TP can be prevented by oral sex. CONCLUSION: The conclusion drawn was that learners are aware of the measures for preventing TP. PMID- 27380837 TI - Substance use amongst secondary school students in a rural setting in South Africa: Prevalence and possible contributing factors. AB - INTRODUCTION: This study determined the prevalence of substance abuse amongst rural secondary school learners in a selected province of South Africa. METHODOLOGY: The study adopted a quantitative approach using a descriptive survey design. Data were collected using a self-administered questionnaire from a total of 338 randomly selected learners, age 14 to 18 years, from 10 secondary schools that make up a rural Vhembedzi circuit in the Limpopo Province. Permission to enter the circuit and the schools was obtained from the circuit manager and parents' or learners' informed consent was obtained prior to data collection. RESULTS: The majority of the participants (94% male, 98% female) had never used substances. Most of the learners started using substances between the ages 15 to 20 years. The majority of learners who were using substances were male. Of the respondents, all the female (100%) students reported to have stopped substance abuse. The majority (63% male, 50% female) of the learners tried to stop substance abuse but failed. Most of the learners (72% male, 71% female) did not have family members who were substance users. The majority of the students attested that substances can be easily obtained in their communities or villages. The majority (68%) of the leaners knew that substance abuse is dangerous to health. CONCLUSION AND RECOMMENDATION: Rural secondary school learners in South Africa have a low prevalence rate of substance abuse. Hence, there is a need for a counselling program in each school to provide support and refer such learners to an appropriate institution for rehabilitation. PMID- 27380838 TI - Emergency nurses' ways of coping influence their ability to empower women to move beyond the oppression of intimate partner violence. AB - BACKGROUND: Millennium Developmental Goal 3 (MDG 3) aims at enhancing gender equity and empowerment of women. Emergency nurses who often encounter women injured by their intimate partners are at risk of developing vicarious traumatisation, which may influence their ability to empower women to move beyond the oppression of intimate partner violence. AIM: This article aims to, (1) describe emergency nurses' ways of coping with the exposure to survivors of intimate partner violence, and (2) recommend a way towards effective coping that will enhance emergency nurses' abilities to empower women to move beyond the oppression of intimate partner violence to contribute to the achievement of MDG 3. SETTING: The study was conducted in emergency units of two public hospitals in an urban setting in South Africa. METHOD: A qualitative design and descriptive phenomenological method was used. Emergency nurses working in the setting were purposively sampled and interviewed. The data were analysed by searching for the essence and meaning attached to the exposure of emergency nurses to survivors of intimate partner violence. RESULTS: Emergency nurses' coping responses were either aimed at avoiding or dealing with their exposure to survivors of intimate partner violence. Coping aimed at dealing with the exposure included seeking support, emotion regulation and accommodative coping. CONCLUSION: Emergency nurses employ either effective or ineffective ways of coping. Less effective ways of coping may increase their risk of vicarious and secondary traumatisation, which in turn may influence their ability to empower women to move beyond the oppression of intimate partner violence. PMID- 27380839 TI - Formulating a return-to-work decision for employees with major depressive disorders: occupational therapists' experiences. AB - BACKGROUND: Major depressive disorder (MDD) is worldwide one of the most concerning health problems as it is associated with reduced work productivity and permanent disability. Occupational therapists are often called upon to make a return-to-work decision on employees with MDD in order to facilitate continued employment. Sustaining employment is in alignment with achieving the Millennium Development Goal 1: Eradicating extreme poverty, as it is known that people suffering from mental health disorders are frequently denied employment opportunities leading to reduced financial resources and therefore possible poverty. AIM: This study described occupational therapists' experiences of formulating a return-to workdecision on employees with MDD. It formed part of a larger study. SETTING: Occupational therapists working in vocational rehabilitation or mental health in South Africa with a postgraduate qualification in vocational rehabilitation or mental health participated in the study. METHOD: A qualitative research design was used. Two separate focus groups explored 11 occupational therapists' experiences of formulating a return-to-work decision on employees with MDD. Ethics clearance number: S34/2007. RESULTS: Seven themes emerged, which were, (1) the biographical profile of the employee, (2) point of view of employer, (3) point of view of employee, (4) point of view of occupational therapist, (5) declaring the employee as temporary incapacitated, (6) declaring the employee as permanently incapacitated and (7) employee's level of motivation. CONCLUSION: Occupational therapists ought to have sound knowledge, skill, experience and the ability to collaborate with employees and employers in formulating a return-to-work decision. PMID- 27380840 TI - Strategies to sustain a quality improvement initiative in neonatal resuscitation. AB - BACKGROUND: Many neonatal deaths can be prevented globally through effective resuscitation. South Africa (SA) committed towards attaining the Millennium Development Goal 4 (MDG4) set by the World Health Organization (WHO). However, SA's district hospitals have the highest early neonatal mortality rates. Modifiable and avoidable causes associated with patient-related, administrative and health care provider factors contribute to neonatal mortality. A quality improvement initiative in neonatal resuscitation could contribute towards decreasing neonatal mortality, thereby contributing towards the attainment of the MDG4. AIM: The aim of this study was, (1) to explore and describe the existing situation regarding neonatal resuscitation in a district hospital, (2) to develop strategies to sustain a neonatal resuscitation quality improvement initiative and (3) to decrease neonatal mortality. Changes that occurred and the sustainability of strategies were evaluated. SETTING: A maternity section of a district hospital in South Africa. METHODS: The National Health Service (NHS) Sustainability Model formed the theoretical framework for the study. The Problem Resolving Action Research model was applied and the study was conducted in three cycles. Purposive sampling was used for the quantitative and qualitative aspects of data collection. Data was analysed accordingly. RESULTS: The findings indicated that the strategies formulated and implemented to address factors related to neonatal resuscitation (training, equipment and stock, staff shortages, staff attitude, neonatal transport and protocols) had probable sustainability and contributed towards a reduction in neonatal mortality in the setting. CONCLUSION: These strategies had the probability of sustainability and could potentially improve neonatal outcomes and reduce neonatal mortality to contribute toward South Africa's drive to attain the MDG4. PMID- 27380841 TI - HIV-positive patients' perceptions of care received at a selected antiretroviral therapy clinic in Vhembe district, South Africa. AB - BACKGROUND: Patients' experiences are a reflection of what has happened during the care process and, therefore, provide information about the performance of health care professional workers. They refer to the process of care provision at the antiretroviral therapy (ART) sites. AIM AND SETTING: This article explored the perceptions of HIV-positive patients of care received at the Gateway Clinic of the regional hospital that provides antiretroviral treatment in the Vhembe district. METHODS: A qualitative, explorative and descriptive design was used. A non-probability, convenient sampling method was used to select 20 HIV-positive patients who were above 18 years of age. In-depth individual interviews were used to collect data. Data were analysed through Tech's open coding method. RESULTS: One theme and two sub-themes emerged, namely positive experiences related to the environment and attitudes of health professionals, and negative experiences concerning the practices by health care providers. CONCLUSION: Patients' perceptions of quality of, and satisfaction with, health care may affect health outcomes. Recommendations are made to consider, practice and strengthen the protocols, the standard operating procedures and the principles of infection control in the health facilities. PMID- 27380842 TI - Challenges experienced by South Africa in attaining Millennium Development Goals 4, 5 and 6. AB - BACKGROUND: Despite progress made by other countries worldwide in achieving Millennium Development Goals (MDGs) 4, 5 and 6, South Africa is experiencing a challenge in attaining positive outcomes for these goals. OBJECTIVE AND SETTING: To describe the challenges experienced by South Africa regarding the successful implementation of MDGs 4, 5 and 6. METHODS: An integrative literature review was used to identify and synthesise various streams of literature on the challenges experienced by South Africa in attaining MDGs 4, 5 and 6. RESULTS: The integrative review revealed the following themes: (1) interventions related to child mortality reduction, (2) implementation of maternal mortality reduction strategies, and (3) identified barriers to zero HIV and TB infections and management. CONCLUSION: It is recommended that poverty relief mechanisms be intensified to improve the socio-economic status of women. There is a need for sectoral planning towards maternal health, and training of healthcare workers should emphasise the reduction of maternal deaths. Programmes addressing the reduction of maternal and child mortality rates, HIV, STIs and TB need to be put in place. PMID- 27380843 TI - Male partners' views of involvement in maternal healthcare services at Makhado Municipality clinics, Limpopo Province, South Africa. AB - BACKGROUND: Male partners have a strong influence on pregnant partners' health and their access to care. Their involvement is critical in the delivery and uptake of maternal healthcare services and improving maternal and child health outcomes. AIM: The study sought to determine male partners' views on their involvement in maternal healthcare services. SETTING: The Makhado Municipality's Kutama, Madombidzha and Vleifontein clinics. METHODS: A qualitative study design, which is exploratory, descriptive and contextual in nature, was used. The population comprised 15 men whose partners had been pregnant within the last 2 years. A non-probability, purposive sampling procedure was used. Data were collected via in-depth individual interviews using a voice recorder and an interview schedule guide. Tesch's open coding method was used to analyse data. RESULTS: The findings revealed one major theme, namely that maternal health issues are viewed as a woman'sdomain; and three sub-themes: culture and participation in childbirth, male partners' employment status, and male partners' unwillingness to participate in maternal health issues. CONCLUSIONS: The involvement of male partners in maternal healthcare services, and further research in promoting this activity, should be proposed to policymakers. PMID- 27380844 TI - Challenges faced by professional nurses when implementing the Expanded Programme on Immunisation at rural clinics in Capricorn District, Limpopo. AB - BACKGROUND: Immunisation is the cornerstone of primary healthcare. Apart from the provision of safe water, immunisation remains the most cost-effective public health intervention currently available. Immunisation prevents infectious conditions that are debilitating, fatal and have the potential to cause huge public health burdens, both financially and socially, in South Africa. AIM: To determine the challenges faced by professional nurses when implementing the Expanded Programme on Immunisation (EPI) at rural clinics in Capricorn District, Limpopo Province, South Africa. SETTING: The study was conducted in selected primary healthcare clinics of Capricorn District, Limpopo Province. METHODS: A qualitative explorative descriptive contextual research design was used to gather data related to the challenges faced by professional nurses when implementing EPI at rural clinics in Capricorn District. RESULTS: The findings revealed that professional nurses had knowledge of the programme, but that they experienced several challenges during implementation of EPI that included staff shortages and problems related to maintenance of the vaccines' potency. CONCLUSIONS: The Department of Health as well as the nursing administration should monitor policies and guidelines, and especially maintenance of a cold chain for vaccines, to ensure that they are practised throughout Limpopo Province. The problem of staff shortages also needs to be addressed so that the EPI can achieve its targeted objectives. PMID- 27380845 TI - An exploratory study of the need for curriculum review of Master of Public Health Degree at a Rural-based University in South Africa. AB - BACKGROUND: Master of Public Health (MPH) training programmes were developed worldwide in response to the crisis in human resources for health. AIM: To determine whether the MPH programme at the selected rural-based university in South Africa enabled students to achieve the MPH core competencies relevant for Lower Middle Income Countries. SETTING: The study was carried out at a rural based University in South Africa. The target population was the 2011 first-year cohort of MPH students who by the beginning of 2014 had just completed their coursework. METHODOLOGY: A quantitative cross-sectional descriptive research design was adapted. Eighty-five students were randomly selected to participate in the study. A structured questionnaire comprising seven competency clusters was developed. The selected students completed a self-administered questionnaire. Only those students who signed consent forms participated in this study. The questionnaire was tested for construct validity and reliability using 10 students with similar characteristics to those sampled for the study. Microsoft Excel software was used to analyse the data descriptively in terms of frequency and percentages. RESULTS: The students were confident of their competencies regarding public health science skills. Amongst these were analytical assessment, communication, community and intersectorial competencies as well as ethics. However, the students lacked confidence in contextsensitive issues, planning and management, research and development, and leadership competencies. Yet the latter is the backbone of public health practice. CONCLUSION AND RECOMMENDATION: There is a need for revamping public health curricula. In this respect, a follow-up study that builds a deeper understanding of the subject is needed. PMID- 27380846 TI - Beliefs and practices of diabetic patients in Vhembe district of Limpopo Province. AB - BACKGROUND: Diabetes mellitus (DM) is a chronic condition affecting over 18 million people worldwide. It can lead to debilitating complications and premature death if not effectively controlled. South Africa, like any sub-Saharan countries and the world at large, is no exception. The prevalence of diabetes among South African adults has increased by 50% from 2009 to date, and an increase of some 11 million new diabetes diagnoses is expected by the year 2020. PURPOSE: The purpose of this study was to describe the beliefs and management practices of patients with DM in Vhembe district, Limpopo province. SETTING: The study was conducted at Vhembe district clinics. METHODS: A probability, purposive sampling was used to sample 100 diabetic patients. Data were collected using a pre-tested questionnaire. Data were analysed using the Statistical Package for Social Sciences version 19.0. Descriptive statistics, frequencies, and percentages were used to summarise the data from the study. RESULTS: The majority of the respondents had poor management practice of feet care and annual eye examinations. Twenty four (24.0%) of the respondents believed that DM can be cured and 22 (22.0%) did not believe that diet helps in the management of DM. CONCLUSION: The belief that DM is curable can have a negative effect as patients can quit taking treatment once the disease is under control. This happens irrespective of the national guidelines for the management of DM. Therefore, some strategies should be sought that could enhance the implementation of the guidelines in order to combat the disease. PMID- 27380847 TI - Factors affecting integration of midwifery nursing science theory with clinical practice in Vhembe District, Limpopo Province as perceived by professional midwives. AB - BACKGROUND: Professional midwives have an important role to play in midwifery training to produce a competent midwife. According to the social learning theory, professional midwives act as role models for students. When allocated for clinical learning experiences in the training hospitals, students will have the opportunity to observe the well-trained, skilled, and experienced professional midwives. The whole process will enable students to integrate theory with practice and they will become competent. AIM: The aim of this study was to determine the factors affecting integration of midwifery nursing science theory with clinical practice as perceived by midwives. SETTING: The study was conducted at the training hospitals in Vhembe district of the Limpopo Province, South Africa. These hospitals were: Donald Fraser, Siloam, and Tshidzini. METHODS: A qualitative explorative, descriptive and contextual design was used. A Nonprobability, convenient sampling method was used to select 11 midwives from the following hospitals: Donald Fraser, Siloam, and Tshidzini, in Vhembe district. In-depth individual interviews were conducted. Data were analysed through open coding method. RESULT: One theme and five sub-themes emerged from the analysed data, namely: shortage of midwives, attitudes towards student midwives, reluctance to perform teaching functions, language barriers, and declining midwifery practice standards. CONCLUSION: Shortage of midwives in the clinical areas led to fewer numbers of mentors whom the students could observe and imitate to acquire clinical skills. Some of the midwives were reluctant to teach students. Recommendations were made for both training institutions and hospitals to employ preceptors for students in the clinical practical. PMID- 27380848 TI - Zero new HIV infections: Mission impossible with current perceptions of young adults in Vhembe District regarding condom use. AB - BACKGROUND: Millennium Development Goal (MDG) number 6, target 6A focuses on halting and reversing the spread of HIV by 2015. South Africa is amongst the 189 countries that are involved in trying to meet the MDGs. In order to try and achieve this goal, South Africa, through its HIV and AIDS, STI and TB strategic plans has adopted the United Nations vision of 'Zeros', which include zero new HIV infections by the year 2015. One of the key interventions for achieving this is improvement in access to condoms. AIM: This article reports on perceptions of Vhembe District young adults regarding condom use. SETTING: This study was conducted in one of the rural clinics in Vhembe District of the Limpopo Province: South Africa. METHODS: A quantitative, cross-sectional design approach was followed. Data were collected using structured questionnaires administered to 372 young adults who came for healthcare services at one of the clinics in Vhembe District. RESULTS: The findings indicated that there is a relationship between positive perceptions toward condom use and actual condom use. People who have positive attitudes toward condoms are also more likely to use them. In contrast, people with a negative attitude towards condoms are less likely to use them during sexual intercourse. Negative attitudes of health care providers were found to be a barrier that prevents sexually active individuals to access condoms in primary health care facilities. CONCLUSION: With current peceptions towards condom use, Zero new HIV infection will never be achieved. The researcher recommends development of strategies for promoting access and correct use of condoms. PMID- 27380849 TI - Views of teenagers on termination of pregnancy at Muyexe high school in Mopani District, Limpopo Province, South Africa. AB - BACKGROUND: Teenage pregnancy is a global social health concern especially because of the HIV and AIDS pandemic, sexually transmitted infections, high rate of termination of pregnancy (TOP), adolescents' parenthood and decreased level of contraceptives. AIM: To explore the views of teenagers on the TOP at Muyexe high school in a rural village of Mopani District, Limpopo Province. SETTING: Muyexe high school in a rural village of Mopani District, Limpopo Province, in South Africa. METHODOLOGY: A qualitative method using explorative and descriptive designs was used to find in-depth description and understanding of teenagers' views on TOP. The target population was girls aged 15-19 years at Muyexe high school in Mopani District. Non-probability, convenient sampling was used to select high school teenage girls who had undergone TOP for the study. Data were collected using individual self-report technique (interview). Tesch's eight steps of qualitative data analysis were used. Measures to ensure trustworthiness and ethical considerations were observed. RESULTS: Two major themes were revealed: (1) Views of teenagers regarding TOP (poverty, relationship problems and single parenthood, negative impact on the teen's life while attending school) and (2) teenager's fears regarding pregnancy (stigma, fear of parents and friends, rape and incest and fear of giving birth). CONCLUSION: Majority of participants had knowledge about TOP; some had experiences about TOP while others held inadequate knowledge. Recommendations were based on the findings by teaching dangers of TOP and various contraceptive methods to prevent unwanted pregnancies and TOP. PMID- 27380850 TI - Factors contributing to the low uptake of medical male circumcision in Mutare Rural District, Zimbabwe. AB - BACKGROUND: Medical male circumcision (MMC) has become a significant dimension of HIV prevention interventions, after the results of three randomised controlled trials in Uganda, South Africa and Kenya demonstrated that circumcision has a protective effect against contracting HIV of up to 60%. Following recommendations by the World Health Organization, Zimbabwe in 2009 adopted voluntary MMC as an additional HIV prevention strategy to the existing ABC behaviour change model. PURPOSE: The purpose of this study is thus to investigate the factors contributing to the low uptake of MMC. METHODS: The study was a quantitative cross-sectional survey conducted in Mutare rural district, Zimbabwe. Questionnaires with open- and closed-ended questions were administered to the eligible respondents. The target population were male participants aged 15-29 who met the inclusion criteria. The households were systematically selected with a sample size of 234. Statistical Package for the Social Sciences was used to analyse the data. RESULTS: Socioculturally, circumcised men are viewed as worthless (37%), shameful (30%) and are tainted as promiscuous (20%), psychological factors reported were infection and delayed healing (39%), being ashamed and dehumanised (58%), stigmatised and discriminated (40.2%) and fear of having an erection during treatment period (89.7%) whilst socio-economic factors were not having time, as it will take their time from work (58%) and complications may arise leading to spending money on treatment (84%). CONCLUSION: Knowledge deficits regarding male medical circumcision lead to low uptake, education on male medical circumcision and its benefits. Comprehensive sexual health education should target men and dispel negative attitudes related to the use of health services. PMID- 27380851 TI - Factors contributing to men's reluctance to seek HIV counselling and testing at Primary Health Care facilities in Vhembe District of South Africa. AB - BACKGROUND: Voluntary HIV antibody Counselling and Testing (HCT) is a cornerstone of HIV prevention in South Africa because it has the potential to prevent HIV transmission. The government of South Africa has for a long time been investing heavily in fighting the spread of HIV and/or AIDS. However, men rarely utilise this service. AIM: The aim of this study was to explore the factors contributing to the reluctance of men to seek HCT in the primary health facilities in Vhembe District. SETTING: The study was conducted at Vhembe District health offices in Limpopo, South Africa. METHODS: A qualitative research design, anchored on semi structured interviews as a method of data collection, was used. Fifteen men working at Vhembe health offices were purposively sampled. Data were analysed using the TECHS's 8 steps method. The approval from Polokwane Provincial offices was guaranteed with participants being protected and respected throughout the study. RESULTS: The response rate per question was 100% with all 15 participants willing to answer all the raised questions though with different views and opinions. The majority of the interviewees indicated that they were aware of HCT services. Stigma as a societal reaction to disease, governmental policies, and attitudinal factors made men refrain from seeking counselling and testing from public health facilities. CONCLUSION: There was a high level of HCT awareness among men in Vhembe District. However, attitudinal and political barriers, stigma, and cultural practices such as circumcision were cited as the reasons for the low level utilisation of HCT services. PMID- 27380852 TI - Evidence of application of the Basic Antenatal Care principles of good care and guidelines in pregnant women's antenatal care records. AB - BACKGROUND: Basic Antenatal Care (BANC) is an approach that is used in the public health institutions of South Africa to provide health care services to pregnant women. The approach was introduced as a quality improvement strategy based on the belief that good quality Antenatal Care (ANC) could reduce maternal and perinatal mortalities and improve maternal health. AIM: The aim of this study was to analyse pregnant women's ANC records for evidence suggesting that the BANC principles of good care and guidelines were being applied. SETTING: The study was conducted in the 12 primary health care clinics that were providing ANC services using the BANC approach in eThekwini district, KwaZulu-Natal. METHODS: A cross sectional quantitative design was used to conduct the study. Data were collected through retrospective record review of 1200 maternity case records of the pregnant women who had attended for ANC services three or more times and was analysed using Statistical Package for Social Sciences (SPSS) version 21.0. RESULTS: The majority of the processes detailed in the guidelines and principles of good care were evident in the records. However, several were missing or recorded in few reviews. These included the ANC plan, delivery plan, midwives' counter signatures on the cards, assessment for foetal congenital abnormalities, and consent for HIV testing. CONCLUSION: The study identified evidence of incomplete application of the BANC principles of good care and guidelines in pregnant women's antenatal care records which indicated that the BANC approach was not being successfully implemented. Recommendations were made with regards to policy development, institutional management and practise, nursing education, and further research to assist in successful implementation of the BANC approach in line with the guidelines and principles of good care. PMID- 27380854 TI - Self-reported impact of caregiving on voluntary home-based caregivers in Mutale Municipality, South Africa. AB - BACKGROUND: The establishment of home-based care (HBC) programmes in developing countries has resulted in a shift of burden from hospitals to communities where palliative care is provided by voluntary home-based caregivers. AIM: The study investigated the impact of caregiving on voluntary home-based caregivers. SETTING: The study was conducted at HBC organisations located in Mutale Municipality of Limpopo Province, South Africa. METHODS: A quantitative cross sectional descriptive survey design was applied to investigate the impact of caregiving on voluntary home-based caregivers. The sample was comprised of (N = 190) home-based caregivers. Home-based caregivers provide care to people in need of care in their homes, such as orphans, the elderly and those suffering from chronic illnesses such as tuberculosis, HIV and/or AIDS, cancer and stroke. Self administered questionnaires were used to collect data which were analysed descriptively using the Statistical Package for the Social Sciences software, Version 20. RESULTS: The results showed that 101 (53.2%) participants were worried about their financial security because they were not registered as workers, whilst 74 (39.0%) participants were always worried about getting infection from their clients because they often do not have protective equipment. CONCLUSION: Voluntary home-based caregivers have an important role in the provision of palliative care to people in their own homes, and therefore, the negative caregiving impact on the lives of caregivers may compromise the provision of quality palliative care. PMID- 27380853 TI - The constraints and concerns regarding the size and/or shape of the second generation female condom: The narratives from the healthcare providers. AB - BACKGROUND: Despite the redesigning of the Reality condom (FC) to a new version of the second generation female condom commonly known as (FC2), the users are persistently constrained and concerned about the size and shape of this new version. Condom use is aligned to the Millennium Development Goals (MDG) 3, 5 and 6, which address gender equality, improving maternal health and preventing HIV and AIDS. AIM: To explore and describe the constraints and concerns regarding the size and/or shape of the FC2. SETTING: The study was conducted at Tshwane health district in Gauteng province. METHODS: A qualitative exploratory descriptive design was used. Individual in-depth interviews that yielded narratives in a designated health district in South Africa were conducted. RESULTS: From the analysis of narratives three specific themes emerged. Firstly, the specific theme was that the size and shape of FC2 is undesirable for the health care providers, which may lead women to contract HIV and AIDS. The second theme was that the size and shape of FC2 and female genitals makes insertion complicated and predisposes women to be vulnerable in sexual relationships. The third was that the size and shape of FC2 results in pain and discomfort during coitus, exposing women to unwanted pregnancies and HIV and AIDS. CONCLUSIONS: The findings indicated the need for an evocative collaborative, interdisciplinary 'walk the talk' sexual health and AIDS education training programme for health care providers in primary health care facilities. Such programmes, if maintained, may assist health care providers to achieve the MDG 3, 5 and 6. PMID- 27380855 TI - Factors influencing weight control practices amongst the adolescent girls in Vhembe District of Limpopo Province, South Africa. AB - BACKGROUND: The incidence of overweight is increasing amongst adolescents in many countries around the world. Healthy and unhealthy weight control practices are common amongst overweight and non-overweight adolescents. AIM: The aim of this study was to explore factors influencing weight control practices amongst adolescent girls. SETTING: The study was conducted at selected secondary schools of Vhembe District of Limpopo Province, South Africa. METHODS: A qualitative, exploratory, descriptive and contextual design was used. Nonprobability, purposive sampling was used to select adolescents who are practicing weight control. In-depth interviews were conducted with 30 participants. Data were analysed according to Tesch's open-coding method. RESULTS: This study revealed that adolescent girls are influenced by a variety of factors to control their weights. These included individual factors, such as body image dissatisfaction; family factors, caused by parental criticism about adolescent weight; and environmental factors, which contain peer group endorsement of dieting. CONCLUSION: Adolescents are exposed to many unhealthy weight control practices, as a way of controlling excess weight. So it is of importance for healthcare providers to make them aware of healthy practices. PMID- 27380856 TI - Perceptions and experiences of allopathic health practitioners on collaboration with traditional health practitioners in post-apartheid South Africa. AB - BACKGROUND: The indigenous health system was perceived to be a threat to the allopathic health system. It was associated with 'witchcraft', and actively discouraged, and repressed through prohibition laws. The introduction of the Traditional Health Practitioners Act No 22 of 2007 brought hope that those centuries of disrespect for traditional health systems would change. The study examined the perceptions and experiences of allopathic health practitioners on collaboration with traditional health practitioners in post-apartheid South Africa. METHODS: Qualitative descriptive research methodology was used to collect data from allopathic health practitioners employed by Limpopo's Department of Health. In-depth focus group discussions and meetings were conducted between January and August 2014. Perceptions and experiences of working with traditional health practitioners were explored. Ethical clearance was obtained from the University of Pretoria and approval from the Department's Research Committee. RESULTS: Dominant views were that the two health systems were not compatible with respect to the science involved and the source of knowledge. Overall, quality of health care will be compromised if traditional health practitioners are allowed to work in public health facilities. CONCLUSION: Allopathic health practitioners do not appear ready to work with traditional health practitioners, citing challenges of quality of health care, differences regarding concept of sciences and source of knowledge; and lack of policy on collaboration. Lack of exposure to traditional medicine seems to impede opportunities to accept and work with traditional healers. Exposure and training at undergraduate level regarding the traditional health system is recommended. Policy guidelines on collaborations are urgently required. PMID- 27380857 TI - Knowledge, attitudes and practices regarding cervical cancer prevention at Thulamela Municipality of Vhembe District in Limpopo Province. AB - BACKGROUND: Cervical cancer is a widespread and often fatal disease that affected 1 million women globally in 2005. Not only is it the second most common cancer in women but it was also the second leading cause of cancer deaths, accounting for over 250 000 in 2006. PURPOSE: The purpose of the study was to assess the knowledge, attitudes and practices regarding cervical cancer prevention among rural women in Vhembe District in Limpopo Province. METHODOLOGY: A quantitative descriptive approach was adopted. The quantitative design enabled the discovery of more information by means of direct questioning of a sample of women aged 30 years and older. A convenience sampling was used to select the respondents. Data were analysed using the Statistical Package for Social Sciences. Measures to ensure ethical issues were adhered to. RESULTS: The findings revealed that women lacked knowledge about cervical cancer and preventive methods, and displayed positive attitudes to the use of services if made available as health workers did not adequately inform them about the availability of the services. CONCLUSION: The awareness of cervical cancer among women in Vhembe District is limited. There is a need to educate and promote awareness of cervical cancer among women to reduce the burden of morbidity and mortality. PMID- 27380858 TI - Adherence to antiretroviral therapy among HIV and AIDS patients at the Kwa-Thema clinic in Gauteng Province, South Africa. AB - BACKGROUND: Introduction of antiretroviral therapy (ART) has shown reduction in HIV-related mortality and morbidity in people living with HIV and AIDS. Since high levels of adherence of more than 95.0% is required to achieve effective suppression of viral load, researchers found it important to establish whether people are pursuing what is expected of them. AIM AND SETTING: The study was aimed at determining adherence to ART among HIV and AIDS patients at the Kwa Thema clinic in Gauteng Province. METHODS: Quantitative cross-sectional descriptive design was used. Ethical clearance was sort from MEDUNSA Research Ethics Committee. Validity and reliability were maintained throughout the study. A non-probability systematic sampling was used. Data were collected using administered structured questionnaire, and a total of 290 respondents were involved. Data were analysed using SPSS software version 22. RESULTS: The findings indicated that the adherence to ART was 77.0%. Factors that were significantly associated with adherence were gender ( chi2 = 3.78, df = 1, p < 0.05), level of education ( chi2 = 3.52, df = 3, p = 0.032), co-treatment of HIV and other infections ( chi2 = 5.46, df = 4, p = 0.019), ability to follow ART ( chi2 = 12.82, df = 1, p = 0.000 < 0.05), and types of antiretroviral drugs. RECOMMENDATION: The study recommends intensification of health education campaign against stigma and gender discrimination. Providing feedback to patients regarding benefits of ART is important. CONCLUSION: The study concluded that adherence to ART at the Kwa-Thema clinic was suboptimal (less than 95%) at 77%, but comparable with the adherence levels in other developing countries. PMID- 27380859 TI - Survey of bar-lounges and restaurants regarding compliance with the current smoke free regulation in Thulamela Municipality, South Africa. AB - BACKGROUND: The Tobacco Products Control Act, No. 83 of 1993 was introduced in South Africa in 1993. Due to the shortfalls of the 1993 Act, the Tobacco Products Control Amendment Act, No. 12 of 1999 was passed in 1999. The regulation relating to smoking of tobacco products in public places was gazetted in 2000 and implemented in 2001. SETTING: The setting for the study was all selected registered licensed bar-lounges including restaurants within the municipality. PURPOSE OF THE STUDY: To examine compliance levels with the current smoke-free regulation at bar-lounges and restaurants in Thulamela Municipality. OBJECTIVES OF THE STUDY: To observe whether structural alterations had been effected to accommodate smoking patrons. To observe whether tobacco-related litter was present in nonsmoking areas and in the outdoor areas within 5 meters of windows and entry ways. To observe whether individuals or groups engaged in smoking in non-smoking areas. METHODS: An observational survey was conducted to measure the level of compliance by lounges and restaurants in Thulamela Municipality. A convenience sampling method was used to sample 56 bar-lounges, including restaurants. Data were collected using an observation log. Collected data were analysed using SPSS 20.0. RESULTS: The study findings noted low compliance with the legislation with only one establishment (1.8%) complying with the requirements of the legislation. CONCLUSION: The level of compliance with the legislation is in a very low state in Thulamela Municipality. Further research is needed to explore factors influencing non-compliance with the regulation. PMID- 27380860 TI - Assessment of learners' exposure to health education and promotion at school in the Limpopo Province of South Africa. AB - BACKGROUND: School participation and educational attainment among adolescents have been rising rapidly in the developing world. Thus, to attain Millennium Development Goal 6 (Combat HIV and/or AIDs, malaria and other diseases), it is crucial to seize the opportunity to educate and encourage teenagers about healthy choices and proper social behaviours that will continue into adulthood. AIM: This study aimed to assess the exposure of rural secondary school learners to health education and promotion at schools in the Limpopo Province of South Africa. SETTING: This study was carried out at 10 secondary schools in Vhumbedzi educational circuit. METHODOLOGY: The study adopted a cross-sectional quantitative approach. Data were collected from 338 randomly selected learners from 10 secondary schools that make up a rural Vhumbedzi circuit in the Limpopo province. A self-administered questionnaire was used to collect data. RESULTS: The findings showed that, 102 (66.07%) male and 121 (67.60%) female learners reported that they were taught about physical changes that occur during adolescence. In the same vein, most of the participants (n = 128, 84.39%) and (n = 152, 85.39%) males and females respectively claimed to have been taught about sexually transmitted diseases. CONCLUSION: In this study the secondary schools in the Limpopo Province of South Africa are making efforts to uphold and expose their learners to health education and promotion at school.Keyword: Health education and promotion, adolescents, school, learners. PMID- 27380861 TI - Development and validation of multivariable predictive model for thromboembolic events in lymphoma patients. AB - Lymphoma patients are at increased risk of thromboembolic events but thromboprophylaxis in these patients is largely underused. We sought to develop and validate a simple model, based on individual clinical and laboratory patient characteristics that would designate lymphoma patients at risk for thromboembolic event. The study population included 1,820 lymphoma patients who were treated in the Lymphoma Departments at the Clinics of Hematology, Clinical Center of Serbia and Clinical Center Kragujevac. The model was developed using data from a derivation cohort (n = 1,236), and further assessed in the validation cohort (n = 584). Sixty-five patients (5.3%) in the derivation cohort and 34 (5.8%) patients in the validation cohort developed thromboembolic events. The variables independently associated with risk for thromboembolism were: previous venous and/or arterial events, mediastinal involvement, BMI>30 kg/m(2) , reduced mobility, extranodal localization, development of neutropenia and hemoglobin level < 100g/L. Based on the risk model score, the population was divided into the following risk categories: low (score 0-1), intermediate (score 2-3), and high (score >3). For patients classified at risk (intermediate and high-risk scores), the model produced negative predictive value of 98.5%, positive predictive value of 25.1%, sensitivity of 75.4%, and specificity of 87.5%. A high risk score had positive predictive value of 65.2%. The diagnostic performance measures retained similar values in the validation cohort. Developed prognostic Thrombosis Lymphoma - ThroLy score is more specific for lymphoma patients than any other available score targeting thrombosis in cancer patients. Am. J. Hematol. 91:1014-1019, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27380862 TI - Clinical efficacy and safety of 20% glycolic peel, 15% lactic peel, and topical 20% vitamin C in constitutional type of periorbital melanosis: a comparative study. AB - INTRODUCTION: Periorbital Melanosis (POM) is a very common esthetic condition, yet there is no definite treatment modality. Topical therapy is the mainstay of treatment which includes chemical peels, vitamin C, and other depigmenting agents. OBJECTIVE: To compare clinical efficacy, safety, and tolerability of 20% glycolic acid peels, 15% lactic acid peels, and topical 20% vitamin C in treatment of constitutional type of POM in Indian patients. METHOD: Ninety patients of constitutional POM were enrolled for 12 weeks. The patients were distributed into three groups. One-third of patients underwent 3-weekly GA peel, another one-third underwent 3-weekly lactic peel, and rest applied vitamin C daily. Clinical improvement was assessed objectively using POM grading. Patient's and physicians global assessment along with patient's global tolerance was also evaluated. RESULTS: More than 50% improvement in POM was observed in 73.34% of patients on GA peel, 56.67% on lactic peel, and 26.67% on vitamin C. On comparing improvement with respect to duration of therapy, GA peel was significantly more effective than lactic peel from 12 weeks onward, while it was more effective than vitamin C from 6 weeks onward. Lactic peel was more effective than vitamin C from 6 weeks onward. Physician and patient global assessment was excellent with glycolic peel followed by lactic peel and vitamin C. The incidence of adverse effect was maximum with GA peel followed by lactic peel and vitamin C. CONCLUSION: Glycolic peel was best among the three modalities, although it was associated with increased rate of side effects. PMID- 27380863 TI - A call for research in early intervention and biological changes during the course of affective disorders: a comment on the review by Robert M. Post. PMID- 27380864 TI - Protocol for Autologous Fat Grafting for Immediate Reconstruction of Lumpectomy Defects Following Surgery for Breast Cancer. AB - BACKGROUND: For women undergoing breast conservative surgery or lumpectomy for early stage breast carcinoma, there are limited options for reconstruction. Options include the use of flap surgery and/or implants, and have a significant associated morbidity and cost. Autologous fat grafting is a new alternative that can achieve a good cosmetic result, while reducing patient morbidity and cost by avoiding more extensive surgery. OBJECTIVE: The primary objectives are to assess patient satisfaction using the Breast-Q questionnaire and to evaluate fat graft volume. The secondary objectives are fat survival and assessment for complication (eg, fat necrosis, cysts), local recurrence, and the number of sessions needed for a satisfactory outcome. METHODS: This study is a case series of 100 patients, at a single-center institute spanning one year. The inclusion criteria include: female sex, age 18 to 75, early state breast cancer (confirmed on ultrasound/ positron emission tomography-computed tomography and cytology), amenable to breast conservative surgery, and at least 6 months post-completion of radiotherapy/ hormone/chemotherapy. Exclusion criteria include patients with more advanced stages of breast cancer necessitating total mastectomy, those unsuitable for surgical excision, and those in whom lumpectomy is not feasible. The patients will have follow-up data collected at 6 months, 12 months and 5 years post operatively. RESULTS: This study will begin enrolment in January 2017. We anticipate that there will be good patient satisfaction with fat grafting. The risk for long-term breast cancer recurrence hasn't been evaluated extensively in literature, however some clinical studies have shown no increased risk of breast cancer in appropriately selected patients at one year. Although some patients may develop complications from fat grafting (eg, necrosis/cysts) this should not confuse the radiological detection of breast cancer recurrence. CONCLUSIONS: Fat grafting is proving to be a viable option for reconstruction of lumpectomy defects with good patient satisfaction. The heterogeneous methods of reporting the harvesting of fat in literature may account for the variable outcomes described, and makes it difficult to compare results with similar studies. The long-term risk of breast cancer recurrence with fat grafting for lumpectomy defects is unknown. PMID- 27380865 TI - Self-Sufficient Formaldehyde-to-Methanol Conversion by Organometallic Formaldehyde Dismutase Mimic. AB - The catalytic networks of methylotrophic organisms, featuring redox enzymes for the activation of one-carbon moieties, can serve as great inspiration in the development of novel homogeneously catalyzed pathways for the interconversion of C1 molecules at ambient conditions. An imidazolium-tagged arene-ruthenium complex was identified as an effective functional mimic of the bacterial formaldehyde dismutase, which provides a new and highly selective route for the conversion of formaldehyde to methanol in absence of any external reducing agents. Moreover, secondary amines are reductively methylated by the organometallic dismutase mimic in a redox self-sufficient manner with formaldehyde acting both as carbon source and reducing agent. PMID- 27380866 TI - Synthesis and immunological evaluation of MUC1 glycopeptide conjugates bearing N acetyl modified STn derivatives as anticancer vaccines. AB - Glycoprotein MUC1 is an attractive target for anti-tumor vaccine development. However, the weak immunogenicity of MUC1 remains a significant problem. To solve this problem, several STn derivatives with N-acetyl modifications were synthesized and incorporated into a 20-amino acid MUC1 tandem repeat sequence. The modified STn-MUC1 glycopeptides were further connected to a carrier protein keyhole limpet hemocyanin (KLH). The immunological effects of these synthetic vaccine conjugates were evaluated using the BALB/c mouse model. The results showed that vaccine V2 elicited higher titers of antibodies which cross-reacted with the native STn-MUC1 antigen. Moreover, the elicited antisera reacted with the STn-MUC1 antigen-positive tumor cells, indicating that the carbohydrate antigen modification strategy may hold potential to overcome the weak immunogenicity of natural MUC1 glycopeptides. PMID- 27380867 TI - Gated-sted microscopy with subnanosecond pulsed fiber laser for reducing photobleaching. AB - The spatial resolution of a stimulated emission depletion (STED) microscope is theoretically unlimited and practically determined by the signal-to-noise ratio. Typically, an increase of the STED beam's power leads to an improvement of the effective resolution. However, this improvement may vanish because an increased STED beam's power is often accompanied by an increased photobleaching, which worsen the effective resolution by reducing the signal strength. A way to lower the photobleaching in pulsed STED (P-STED) implementations is to reduce the peak intensity lengthening the pulses duration (for a given average STED beam's power). This also leads to a reduction of the fluorophores quenching, thus a reduction of the effective resolution, but the time-gated detection was proved to be successful in recovering these reductions. Here we demonstrated that a subnanosecond fiber laser beam (pulse width ~600 ps) reduces the photobleaching with respect to a traditional stretched hundreds picosecond (~200 ps) beam provided by a Ti:Sapphire laser, without any effective spatial resolution lost. PMID- 27380868 TI - Persistence of aroma volatiles in the oral and nasal cavities: real-time monitoring of decay rate in air exhaled through the nose and mouth. AB - The persistence of aroma compounds in breath after swallowing is an important attribute of the overall aroma experience during eating and drinking. It is mainly related to the coating of the oral tract with food residues and the interaction between volatile compounds and airway mucosa. We have studied the persistence of eight compounds (2,5-dimethylpyrazine, guaiacol, 4-methylguaiacol, phenylethylalcohol, ethylbutanoate, ethyloctanoate, isoamylacetate and 2 heptanone) both in-nose and in-mouth after administration of volatiles in gas phase (vapor) to five different panelists. By using volatiles in the gas phase, only the interaction with the mucosa is highlighted and the formation of a liquid coating in the oral and tracheal airway is avoided. The physicochemical properties of the compounds, mainly polarity and vapor pressure, determine the interactions of the volatiles with the airway mucosa. The use of different breathing protocols allowed the study of the differences between nasal and oral mucosa in volatile retention, with higher persistence of volatiles obtained in mouth. Initial concentration also affected persistence, but only for compounds with high volatility and at low concentration. PMID- 27380869 TI - Efficacy of Ultrasound-Guided Axillary Brachial Plexus Block for Analgesia During Percutaneous Transluminal Angioplasty for Dialysis Access. AB - PURPOSE: To evaluate the efficacy and safety of ultrasound (US)-guided axillary brachial plexus block (ABPB) for analgesia during percutaneous transluminal angioplasty (PTA) for dialysis access. SUBJECTS AND METHODS: Twenty-one patients who underwent PTA for stenotic dialysis access shunts and who had previous experience of PTA without sedation, analgesia, and anesthesia were included. The access type in all patients was native arteriovenous fistulae in the forearm. Two radiologists performed US-guided ABPB for the radial and musculocutaneous nerves before PTA. The patients' pain scores were evaluated using a visual analog scale (VAS) after PTA, and these were compared with previous sessions without US-guided ABPB. The patient's motor/sensory paralysis after PTA was also examined. RESULTS: The mean time required to achieve US-guided ABPB was 8 min. The success rate of this procedure was 100 %, and there were no significant complications. All 21 patients reported lower VAS with US-guided ABPB as compared to without the block (p < 0.01). All patients expressed the desire for an ABPB for future PTA sessions, if required. Transient motor paralysis occurred in 8 patients, but resolved in all after 60 min. CONCLUSION: US-guided ABPB is feasible and effective for analgesia in patients undergoing PTA for stenotic dialysis access sites. LEVEL OF EVIDENCE: Level 4 (case series). PMID- 27380870 TI - Early Enlargement of Aneurysmal Sac and Separation of EndoBags of Nellix Endovascular Aneurysm Sealing System as Signs of Increased Risk of Later Aneurysm Rupture. AB - Nellix Endovascular Aneurysm Sealing (EVAS) system is a new concept and technology of abdominal aortic aneurysm (AAA) repair. Elective EVAS using Nellix device was performed for a 83-year-old man with AAA. 2-month post-EVAS CTA surveillance demonstrated mild enlargement of aneurysmal sac and separation of the EndoBags, but without detectable endoleak. The patient developed sudden AAA rupture with retroperitoneal hematoma at about 4 months after EVAS. We postulated that early enlargement of aneurysmal sac and separation of EndoBags of Nellix devices after EVAS, even without detectable endoleak, might indicate significant aneurysmal wall weakening with increased risk of later AAA rupture. To the best of the authors' knowledge, this was the first reported case of aortic rupture after EVAS without detectable endoleak during and after the procedure. PMID- 27380871 TI - Transcatheter Arterial Embolization with a Mixture of Absolute Ethanol and Iodized Oil for Poorly Visualized Endophytic Renal Masses Prior to CT-Guided Percutaneous Cryoablation. AB - PURPOSE: To retrospectively evaluate the feasibility of transcatheter arterial embolization (TAE) using a mixture of absolute ethanol and iodized oil to improve localization of endophytic renal masses on unenhanced computed tomography (CT) prior to CT-guided percutaneous cryoablation (PCA). MATERIALS AND METHODS: Our institutional review board approved this retrospective study. From September 2011 to June 2015, 17 patients (mean age, 66.8 years) with stage T1a endophytic renal masses (mean diameter, 26.5 mm) underwent TAE using a mixture of absolute ethanol and iodized oil to improve visualization of small and endophytic renal masses on unenhanced CT prior to CT-guided PCA. TAE was considered successful that accumulated iodized oil depicted whole of the tumor edge on CT. PCA was considered successful when the iceball covered the entire tumor with over a 5 mm margin. Oncological and renal functional outcomes and complications were also evaluated. RESULTS: TAE was successfully performed in 16 of 17 endophytic tumors. The 16 tumors were performed under CT-guided PCA with their distinct visualization of localization and safe ablated margin. During the mean follow-up period of 15.4 +/- 5.1 months, one patient developed local recurrence. Estimated glomerular filtration rate declined by 8 % with statistical significance (P = 0.01). There was no procedure-related significant complication. CONCLUSION: TAE using a mixture of absolute ethanol and iodized oil to improve visualization of endophytic renal masses facilitated tumor localization on unenhanced CT, permitting depiction of the tumor edge as well as a safe margin for ablation during CT-guided PCA, with an acceptable decline in renal function. PMID- 27380873 TI - Endovascular Repair of a Large Common Femoral Artery Pseudoaneurysm via a Retrograde Deep Femoral Arterial Access. PMID- 27380872 TI - Improved Visibility of Metastatic Disease in the Liver During Intra-Arterial Therapy Using Delayed Arterial Phase Cone-Beam CT. AB - PURPOSE: To compare the visibility of liver metastases on dual-phase cone-beam CT (DP-CBCT) and digital subtraction angiography (DSA), with reference to preinterventional contrast-enhanced magnetic resonance imaging (CE-MRI) of the liver. METHODS: This IRB-approved, retrospective study included 28 patients with neuroendocrine (NELM), colorectal (CRCLM), or sarcoma (SLM) liver metastases who underwent DP-CBCT during intra-arterial therapy (IAT) between 01/2010 and 10/2014. DP-CBCT was acquired after a single contrast agent injection in the tumor-feeding arteries at early and delayed arterial phases (EAP and DAP). The visibility of each lesion was graded by two radiologists in consensus on a three rank scale (complete, partial, none) on DP-CBCT and DSA images using CE-MRI as reference. RESULTS: 47 NELM, 43 CRCLM, and 16 SLM were included. On DSA 85.1, 44.1, and 37.5 % of NELM, CRCLM, and SLM, were at least partially depicted, respectively. EAP-CBCT yielded significantly higher sensitivities of 88.3 and 87.5 % for CRCLM and SLM, respectively (p < 0.01), but not for NELM (89.4 %; p = 1.0). On DAP-CBCT all NELM, CRCLM, and SLM were visible (p < 0.001). Complete depiction was achieved on DSA for 59.6, 16.3, and 18.8 % of NELM, CRCLM, and SLM, respectively. The complete depiction rate on EAP-CBCT was significantly higher for CRCLM (46.5 %; p < 0.001), lower for NELM (40.4 %; p = 0.592), and similar for SLM (25 %, p = 0.399). On DAP-CBCT however, the highest rates of complete depiction were found-NELM (97.8 %; p = 0.008), CRCLM (95.3 %; p = 0.008), and SLM (100 %; p < 0.001). CONCLUSION: DAP-CBCT substantially improved the visibility of liver metastases during IAT. Future studies need to evaluate the clinical impact. PMID- 27380874 TI - Impact of intratumoural heterogeneity on the assessment of Ki67 expression in breast cancer. AB - In breast cancer (BC), the prognostic value of Ki67 expression is well documented. Intratumoural heterogeneity (ITH) of Ki67 expression is amongst the several technical issues behind the lag of its inclusion into BC prognostic work up. The immunohistochemical (IHC) expression of anti-Ki67 antibody (MIB1 clone) was assessed in four full-face (FF) sections from different primary tumour blocks and their matched axillary nodal (LN) metastases in a series of 55 BC. Assessment was made using the highest expression hot spots (HS), lowest expression (LS), and overall/average expression scores (AS) in each section. Heterogeneity score (Hes), co-efficient of variation, and correlation co-efficient were used to assess the levels of Ki67 ITH. Ki67 HS, LS, and AS scores were highly variable within the same section and between different sections of the primary tumour, with maximal variation observed in the LS (P < 0.001). The least variability between the different slides was observed with HS scoring. Although the associations between Ki67 and clinicopathological and molecular variables were similar when using HS or AS, the best correlation between AS and HS was observed in tumours with high Ki67 expression only. Ki67 expression in LN deposits was less heterogeneous than in the primary tumours and was perfectly correlated with the HS Ki67 expression in the primary tumour sections (r = 0.98, P < 0.001). In conclusion, assessment of Ki67 expression using HS scoring method on a full-face BC tissue section can represent the primary tumour growth fraction that is likely to metastasise. The association between Ki67 expression pattern in the LN metastasis and the HS in the primary tumour may reflect the temporal heterogeneity through clonal expansion. PMID- 27380875 TI - Ligation-free ribosome profiling of cell type-specific translation in the brain. AB - Ribosome profiling has emerged as a powerful tool for genome-wide measurements of translation, but library construction requires multiple ligation steps and remains cumbersome relative to more conventional deep-sequencing experiments. We report a new, ligation-free approach to ribosome profiling that does not require ligation. Library construction for ligation-free ribosome profiling can be completed in one day with as little as 1 ng of purified RNA footprints. We apply ligation-free ribosome profiling to mouse brain tissue to identify new patterns of cell type-specific translation and test its ability to identify translational targets of mTOR signaling in the brain. PMID- 27380876 TI - Multihost Bartonella parasites display covert host specificity even when transmitted by generalist vectors. AB - Many parasites infect multiple sympatric host species, and there is a general assumption that parasite transmission between co-occurring host species is commonplace. Such between-species transmission could be key to parasite persistence within a disease reservoir and is consequently an emerging focus for disease control. However, while a growing body of theory indicates the potential importance of between-species transmission for parasite persistence, conclusive empirical evidence from natural communities is lacking, and the assumption that between-species transmission is inevitable may therefore be wrong. We investigated the occurrence of between-species transmission in a well-studied multihost parasite system. We identified the flea-borne Bartonella parasites infecting sympatric populations of Apodemus sylvaticus (wood mice) and Myodes glareolus (bank voles) in the UK and confirmed that several Bartonella species infect both rodent species. However, counter to previous knowledge, genetic characterization of these parasites revealed covert host specificity, where each host species is associated with a distinct assemblage of genetic variants, indicating that between-species transmission is rare. Limited between-species transmission could result from rare encounters between one host species and the parasites infecting another and/or host-parasite incompatibility. We investigated the occurrence of such encounter and compatibility barriers by identifying the flea species associated with each rodent host, and the Bartonella variants carried by individual fleas. We found that the majority of fleas were host generalists but the assemblage of Bartonella variants in fleas tended to reflect the assemblage of Bartonella variants in the host species they were collected from, thus providing evidence of encounter barriers mediated by limited between species flea transfer. However, we also found several fleas that were carrying variants never found in the host species from which they were collected, indicating some degree of host-pathogen incompatibility when barriers to encounter are overcome. Overall, these findings challenge our default perceptions of multihost parasite persistence, as they show that despite considerable overlaps in host species ecology, separate populations of the same parasite species may circulate and persist independently in different sympatric host species. This questions our fundamental understanding of endemic transmission dynamics and the control of infection within natural reservoir communities. PMID- 27380878 TI - Improved Shock Tube Measurement of the CH4 + Ar = CH3 + H + Ar Rate Constant using UV Cavity-Enhanced Absorption Spectroscopy of CH3. AB - We report an improved measurement for the rate constant of methane dissociation in argon (CH4 + Ar = CH3 + H + Ar) behind reflected shock waves. The experiment was conducted using a sub-parts per million sensitivity CH3 diagnostic recently developed in our laboratory based on ultraviolet cavity-enhanced absorption spectroscopy. The high sensitivity of this diagnostic allowed for measurements of quantitatively resolved CH3 time histories during the initial stage of CH4 pyrolysis, where the reaction system is clean and free from influences of secondary reactions and temperature change. This high sensitivity also allowed extension of our measurement range to much lower temperatures (<1500 K). The current-reflected shock measurements were performed at temperatures between 1487 and 1866 K and pressures near 1.7 atm, resulting in the following Arrhenius rate constant expression for the title reaction: k(1.7 atm) = 3.7 * 10(16) exp(-42 200 K/T) cm(3)/mol.s, with a 2sigma uncertainty factor of 1.25. The current data are in good consensus with various theoretical and review studies, but at the low temperature end they suggest a slightly higher (up to 35%) rate constant compared to these previous results. A re-evaluation of previous and current experimental data in the falloff region was also performed, yielding updated expressions for both the low-pressure limit and the high-pressure limit rate constants and improved agreement with all existing data. PMID- 27380877 TI - Cancer stem cell mediated acquired chemoresistance in head and neck cancer can be abrogated by aldehyde dehydrogenase 1 A1 inhibition. AB - Chemoresistance leading to disease relapse is one of the major challenges to improve outcome in head and neck cancers. Cancer Stem Cells (CSCs) are increasingly being implicated in chemotherapy resistance, this study investigates the correlation between CSC behavior and acquired drug resistance in in vitro cell line models. Cell lines resistant to Cisplatin (Cal-27 CisR, Hep-2 CisR) and 5FU (Cal-27 5FUR) with high Resistance Indices (RI) were generated (RI >= 3) by short-term treatment of head and neck squamous cell carcinoma (HNSCC) cell lines with chemotherapeutic drugs (Cisplatin, Docetaxel, 5FU), using a dose-incremental strategy. The cell lines (Cal-27 DoxR, Hep-2 DoxR, Hep-2 5FUR) that showed low RI, nevertheless had a high cross resistance to Cisplatin/5FU (P < 0.05). Cal-27 CisR and DoxR showed 12-14% enrichment of CD44+ cells, while CisR/5FUR showed 4 6% increase in ALDH1A1+ cells as compared to parental cells (P < 0.05). Increased expression of stem cell markers (CD44, CD133, NOTCH1, ALDH1A1, OCT4, SOX2) in these cell lines, correlated with enhanced spheroid/colony formation, migratory potential, and increased in vivo tumor burden (P < 0.05). Inhibition of ALDH1A1 in Cal-27 CisR led to down regulation of the CSC markers, reduction in migratory, self-renewal and tumorigenic potential (P < 0.05) accompanied by an induction of sensitivity to Cisplatin (P < 0.05). Further, ex vivo treatment of explants (n = 4) from HNSCC patients with the inhibitor (NCT-501) in combination with Cisplatin showed a significant decrease in proliferating cells as compared to individual treatment (P = 0.001). This study hence suggests an ALDH1A1-driven, CSC-mediated mechanism in acquired drug resistance of HNSCC, which may have therapeutic implications. (c) 2016 Wiley Periodicals, Inc. PMID- 27380879 TI - Photoresponse of atomically thin MoS2 layers and their planar heterojunctions. AB - MoS2 monolayers exhibit excellent light absorption and large thermoelectric power, which are, however, accompanied by a very strong exciton binding energy - resulting in complex photoresponse characteristics. We study the electrical response to scanning photo-excitation on MoS2 monolayer (1L) and bilayer (2L) devices, and also on monolayer/bilayer (1L/2L) planar heterojunction and monolayer/few-layer/multi-layer (1L/FL/ML) planar double heterojunction devices to unveil the intrinsic mechanisms responsible for photocurrent generation in these materials and junctions. A strong photoresponse modulation is obtained by scanning the position of the laser spot, as a consequence of controlling the relative dominance of a number of layer dependent properties, including (i) the photoelectric effect (PE), (ii) the photothermoelectric effect (PTE), (iii) the excitonic effect, (iv) hot photo-electron injection from metal, and (v) carrier recombination. The monolayer and bilayer devices show a peak photoresponse when the laser is focused at the source junction, while the peak position shifts to the monolayer/few-layer junction in the heterostructure devices. The photoresponse is found to be dependent on the incoming light polarization when the source junction is illuminated, although the polarization sensitivity drastically reduces at the monolayer/few-layer heterojunction. Finally, we investigate the laser position dependent transient response of the photocurrent to reveal that trapping of carriers in SiO2 at the source junction is a critical factor to determine the transient response in 2D photodetectors, and also show that, by a systematic device design, such trapping can be avoided in the heterojunction devices, resulting in a fast transient response. The insights obtained will play an important role in designing a fast 2D TMD based photodetector and related optoelectronic and thermoelectric devices. PMID- 27380881 TI - Suppressing disease spreading by using information diffusion on multiplex networks. AB - Although there is always an interplay between the dynamics of information diffusion and disease spreading, the empirical research on the systemic coevolution mechanisms connecting these two spreading dynamics is still lacking. Here we investigate the coevolution mechanisms and dynamics between information and disease spreading by utilizing real data and a proposed spreading model on multiplex network. Our empirical analysis finds asymmetrical interactions between the information and disease spreading dynamics. Our results obtained from both the theoretical framework and extensive stochastic numerical simulations suggest that an information outbreak can be triggered in a communication network by its own spreading dynamics or by a disease outbreak on a contact network, but that the disease threshold is not affected by information spreading. Our key finding is that there is an optimal information transmission rate that markedly suppresses the disease spreading. We find that the time evolution of the dynamics in the proposed model qualitatively agrees with the real-world spreading processes at the optimal information transmission rate. PMID- 27380882 TI - Comparison of resting and total energy expenditure in peritoneal dialysis patients and body composition measured by dual-energy X-ray absorptiometry. AB - Under basal resting conditions muscle metabolism is reduced, whereas metabolism increases with physical activity. We wished to determine whether there was an association between resting energy expenditure (REE) and total energy expenditure (TEE) in peritoneal dialysis (PD) patients and lean body mass (LBM). We determined REE and TEE by recently validated equations, using doubly labelled isotopic water, and LBM by dual-energy X-ray absorptiometry (DXA) scanning. We studied 87 patients, 50 male (57.4%), 25 diabetic (28.7%), mean age 60.3+/-17.6 years, with a median PD treatment of 11.4 (4.7-29.5) months. The mean weight was 70.1+/-17.7 kg with a REE of 1509+/-245 kcal/day and TEE 1947+/-378 kcal/day. REE was associated with body size (weight r=0.78 and body mass index (BMI) r=0.72) and body composition (LBM r=0.77, lean body mass index (LBMI) r=0.76, r=0.62), all P<0.001). For TEE, there was an association with weight r=0.58, BMI r=0.49 and body composition (LBM r=0.64, LBMI (r=0.54), all P<0.001). We compared LBMI measured by DXA and that estimated by the Boer equation using anthropomorphic measurements, which overestimated and underestimated LBM for smaller patients and heavier patients, respectively. Muscle metabolism is reduced at rest and increases with physical activity. Whereas previous reports based on REE did not show any association with LBM, we found an association between both REE and TEE, using a recently validated equation derived from dialysis patients, and LBM measured by DXA scanning. Estimation of muscle mass from anthropomorphic measurements systematically overestimated LBM for small patients and conversely underestimated for heavier patients. PMID- 27380883 TI - Longitudinal changes in the dietary inflammatory index: an assessment of the inflammatory potential of diet over time in postmenopausal women. AB - BACKGROUND/OBJECTIVES: The dietary inflammatory index (DII) measured at one time point is associated with risk of several chronic diseases, but disease risk may change with longitudinal changes in DII scores. Data are lacking regarding changes in DII scores over time; therefore, we assessed changes in the DII in the Women's Health Initiative (WHI). SUBJECTS/METHODS: DII scores were calculated using data from repeated food frequency questionnaires in the WHI Observational Study (OS; n=76 671) at baseline and year 3, and the WHI Dietary Modification trial (DM; n=48482) at three time points. Lower DII scores represent more anti inflammatory diets. We used generalized estimating equations to compare mean changes in DII over time, adjusting for multiple comparisons, and multivariable adjusted linear regression analyses to determine predictors of DII change. RESULTS: In the OS, mean DII decreased modestly from -1.14 at baseline to -1.50 at year 3. In the DM, DII was -1.32 in year 1, -1.60 in year 3 and -1.48 in year 6 in the intervention arm and was -0.65 in year 1, -0.94 in year 3 and -0.96 in year 6 in the control arm. These changes were modified by body mass index, education and race/ethnicity. A prediction model explained 22% of the variance in the change in DII scores in the OS. CONCLUSIONS: In this prospective investigation of postmenopausal women, reported dietary inflammatory potential decreased modestly over time. Largest reductions were observed in normal-weight, highly educated women. Future research is warranted to examine whether reductions in DII are associated with decreased chronic disease risk. PMID- 27380884 TI - The prebiotic concept and human health: a changing landscape with riboflavin as a novel prebiotic candidate? AB - Emerging evidence suggests that the gut microbiota has a critical role in both the maintenance of human health and the pathogenesis of many diseases. Modifying the colonic microbiota using functional foods has attracted significant research effort and product development. The pioneering concept of prebiotics, as introduced by Gibson and Roberfroid in the 1990s, emphasized the importance of diet in the modulation of the gut microbiota and its relationships to human health. Increasing knowledge of the intestinal microbiota now suggests a more comprehensive definition. This paper briefly reviews the basics of the prebiotic concept with a discussion of recent attempts to refine the concept to open the door for novel prebiotic food ingredients, such as polyphenols, minerals and vitamins. PMID- 27380885 TI - Different displacement of bioimpedance vector due to Ag/AgCl electrode effect. AB - BACKGROUND/OBJECTIVES: Bioelectrical impedance vector analysis (BIVA) is increasingly used in clinical research to assess soft tissue hydration. It is known that physical characteristics of electrodes, such as low intrinsic impedance, low electrode/skin contact impedance and type of gel, affect the reliability of noninvasive bioimpedance assessments. The aim of this study was to determine the effect of intrinsic impedance of electrode on the bioimpedance vector displacement in RXc graph. SUBJECTS/METHODS: The intrinsic impedance is measured in nine pregelled disposable Ag/AgCl electrodes usually used for bioimpedance measures. The BIVA method is performed on 35 healthy volunteers using a 50 kHz phase-sensitive bioimpedance analyzer (BIA 101 Anniversary) with the lowest intrinsic impedance electrode and highest. The individual bioimpedance vector is plotted on the bivariate normal interval of reference population. The differences in the mean bioimpedance vectors obtained with each electrode are plotted, with their 95% confidence ellipses, on the dRXc graph. The paired one sample Hotelling's T2-test is used to compare the differences of the mean bioimpedance vectors. RESULTS: We found large variability in intrinsic resistance (11-665 Omega) and reactance (0.25-2.5 Omega) values of the electrodes analyzed and significant displacement (P<0.05) of bioimpedance vector positions in healthy adults according to the paired one-sample Hotelling's T2-test. CONCLUSIONS: A robust study of all physical characteristics of commercial Ag/AgCl electrodes is necessary to reach consensus on pregelled Ag/AgCl electrodes valid for bioimpedance measurement. This information will enable BIVA users to avoid systemic errors when performing BIVA assessments, specifically when these measurements are used for clinical interpretations. PMID- 27380886 TI - Consumption of soy foods and isoflavones and risk of type 2 diabetes: a pooled analysis of three US cohorts. AB - BACKGROUND/OBJECTIVES: Evidence regarding the consumption of soy foods and isoflavones in relation to risk of type 2 diabetes (T2D) is scarce. Our study was to evaluate the association between soy food and isoflavone consumption and risk of T2D in US men and women. SUBJECTS/METHODS: We followed 63 115 women in the Nurses' Health Study (1998-2012), 79 061 women in the Nurses' Health Study II (1999-2013) and 21 281 men in the Health Professionals Follow-Up Study (2002 2010). Diet was assessed by a validated food-frequency questionnaire and was updated every 4 years. Self-reports of incident T2D were confirmed by a validated supplementary questionnaire. RESULTS: During 1 966 321 person-years of follow-up, 9185 incident T2D cases were documented. After multivariate adjustment for covariates, consumption of soy foods (tofu and soy milk) was not associated with a lower T2D risk. Compared with non-consumers of soy foods, the hazard ratio (HR) was 1.00 (95% confidence interval (CI): 0.93, 1.07) for <1 serving/week and 0.93 (95% CI: 0.83, 1.03) for ?1 serving/week of soy foods (P for trend=0.14). In contrast, intake of total isoflavones was inversely associated with T2D risk. Comparing extreme quintiles of isoflavones, the HR was 0.89 (95% CI: 0.83, 0.96; P for trend=0.009). Inverse associations were also found for consumption of major individual isoflavones, including daidzein and genistein, with risk of T2D. CONCLUSIONS: Intake of isoflavones was associated with a modestly lower T2D risk in US men and women who typically consumed low-to-moderate amounts of soy foods. These findings warrant replications in other populations with similar soy intake levels. PMID- 27380888 TI - Dietary diversity decreases the risk of cognitive decline among Japanese older adults. AB - AIM: To clarify the effectiveness of dietary diversity, calculated by dietary records, on cognitive decline. METHODS: Data were derived from the National Institute for Longevity Sciences - Longitudinal Study of Aging. Participants comprised 298 men and 272 women aged 60-81 years at baseline (second wave) who participated in the follow-up study (third to seventh wave) at least once. Cognitive function was assessed with the Mini-Mental State Examination in all study waves. Dietary diversity was determined using the Quantitative Index for Dietary Diversity based on a 3-day dietary record in the second wave. Cumulative data among participants with a Mini-Mental State Examination score >27 in the second wave were analyzed using a generalized estimating equation. Multivariate adjusted odds ratios and 95% confidence intervals for Mini-Mental State Examination scores <=27 in each study wave according to a 1 standard deviation (increase), or quartiles of the Quantitative Index for Dietary Diversity at baseline, were adjusted for sex, age, follow-up time, baseline Mini-Mental State Examination score, education, body mass index, annual household income, current smoking status, energy intake and disease history. RESULTS: Multivariate adjusted odds ratio for a decline in Mini-Mental State Examination score was 0.79 (95% CI 0.70-0.89; P < 0.001) with a 1 SD increase in dietary diversity score, or 1.00 (reference), 0.99 (95% CI 0.70-1.43), 0.68 (95% CI 0.46-0.99) and 0.56 (95% CI 0.38-0.83) according to the lowest through highest quartiles of dietary diversity score, respectively (trend P = 0.001). CONCLUSIONS: Daily intake of various kinds of food might be a protective factor against cognitive decline in community dwelling Japanese older adults. Geriatr Gerontol Int 2017; 17: 937-944. PMID- 27380889 TI - Integrated hollow microneedle-optofluidic biosensor for therapeutic drug monitoring in sub-nanoliter volumes. AB - Therapeutic drug monitoring (TDM) typically requires painful blood drawn from patients. We propose a painless and minimally-invasive alternative for TDM using hollow microneedles suitable to extract extremely small volumes (<1 nL) of interstitial fluid to measure drug concentrations. The inner lumen of a microneedle is functionalized to be used as a micro-reactor during sample collection to trap and bind target drug candidates during extraction, without requirements of sample transfer. An optofluidic device is integrated with this microneedle to rapidly quantify drug analytes with high sensitivity using a straightforward absorbance scheme. Vancomycin is currently detected by using volumes ranging between 50-100 MUL with a limit of detection (LoD) of 1.35 MUM. The proposed microneedle-optofluidic biosensor can detect vancomycin with a sample volume of 0.6 nL and a LoD of <100 nM, validating this painless point of care system with significant potential to reduce healthcare costs and patients suffering. PMID- 27380887 TI - Genome-wide analysis of DNA methylation during antagonism of DMOG to MnCl2 induced cytotoxicity in the mouse substantia nigra. AB - Exposure to excessive manganese (Mn) causes manganism, a progressive neurodegenerative disorder similar to idiopathic Parkinson's disease (IPD). The detailed mechanisms of Mn neurotoxicity in nerve cells, especially in dopaminergic neurons are not yet fully understood. Meanwhile, it is unknown whether there exists a potential antagonist or effective drug for treating neuron damage in manganism. In the present study, we report the discovery of an HIF prolyl-hydroxylase inhibitor, DMOG [N-(2-Methoxy-2-oxoacetyl) glycine methyl ester], that can partially inhibit manganese toxicity not only in the neuroblastoma cell line SH-SY5Y in vitro but also in a mouse model in vivo. A genome-wide methylation DNA analysis was performed using microarray hybridization. Intriguingly, DNA methylation in the promoter region of 226 genes was found to be regulated by MnCl2, while the methylation effects of MnCl2 could be restored with combinatorial DMOG treatment. Furthermore, we found that genes with converted promoter methylation during DMOG antagonism were associated across several categories of molecular function, including mitochondria integrity maintain, cell cycle and DNA damage response, and ion transportation. Collectively, our results serve as the basis of a mechanism analysis of neuron damage in manganism and may supply possible gene targets for clinical therapy. PMID- 27380890 TI - Preserved antiviral adaptive immunity following polyclonal antibody immunotherapy for severe murine influenza infection. AB - Passive immunotherapy may have particular benefits for the treatment of severe influenza infection in at-risk populations, however little is known of the impact of passive immunotherapy on the formation of memory responses to the virus. Ideally, passive immunotherapy should attenuate the severity of infection while still allowing the formation of adaptive responses to confer protection from future exposure. In this study, we sought to determine if administration of influenza-specific ovine polyclonal antibodies could inhibit adaptive immune responses in a murine model of lethal influenza infection. Ovine polyclonal antibodies generated against recombinant PR8 (H1N1) hemagglutinin exhibited potent prophylactic capacity and reduced lethality in an established influenza infection, particularly when administered intranasally. Surviving mice were also protected against reinfection and generated normal antibody and cytotoxic T lymphocyte responses to the virus. The longevity of ovine polyclonal antibodies was explored with a half-life of over two weeks following a single antibody administration. These findings support the development of an ovine passive polyclonal antibody therapy for treatment of severe influenza infection which does not affect the formation of subsequent acquired immunity to the virus. PMID- 27380891 TI - The Effect of Crystal Face of Fe2O3 on the Electrochemical Performance for Lithium-ion Batteries. AB - Fe2O3 nanorods exposing (001) and (010) plane as well as Fe2O3 nanosheets exposing (001) plane have been successfully synthesized. Fe2O3 nanosheets exhibit better cycle performance and rate capabilities than that of Fe2O3 nanorods. The discharge capacity of Fe2O3 nanosheets can stabilize at 865 mAh/g at the rate of 0.2 C (1C = 1000 mA/g) and 570 mAh/g at the rate of 1.2 C after 80 cycles, which increased by 90% and 79% compared with 456 mAh/g and 318 mAh/g of Fe2O3 nanorods. In comparison with (010) plane, the (001) plane of hematite possesses larger packing density of Fe(3+) and O(2-), which is responsible for the superior electrochemical performances of Fe2O3 nanosheets than that of Fe2O3 nanorods. In addition, potentiostatic intermittent titration (PITT) results show the diffusion coefficients of Li(+) (DLi) of Fe2O3 nanosheets is higher than that of Fe2O3 nanorods. The higher diffusion coefficients of Li(+) is favorable for the excellent lithium-storage capabilities and rate capability of Fe2O3 nanosheets. Inspired by our results, we can design and synthesize Fe2O3 or other electrodes with high performances according to their structure features in future. PMID- 27380893 TI - Hydrogen Sulfide Promotes Surface Insertion of Hippocampal AMPA Receptor GluR1 Subunit via Phosphorylating at Serine-831/Serine-845 Sites Through a Sulfhydration-Dependent Mechanism. AB - AIMS: Hydrogen sulfide (H2 S) has been widely accepted as a gas neuromodulator to regulate synaptic function. Herein, we set out to determine the effect of H2 S on alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) and its mechanism. METHODS: BS(3) protein cross-linking, Western blot, patch clamp, and biotin-switch assay. RESULTS: Bath application of H2 S donor NaHS (50 and 100 MUM) rapidly promoted surface insertion of hippocampal AMPAR GluR1 subunit. This effect can be abolished by dithiothreitol (DTT) and mimicked by Na2 S4 , indicating that a sulfhydration-dependent mechanism may be involved. NaHS increased APMAR-mediated EPSC and led to an elevation of GluR2-lacking AMPAR content. Notably, NaHS did not increase the sulfhydration of AMPAR subunits, but it significantly increased the phosphorylation of GluR1 at serine-831 and serine 845 sites. Postsynaptic signal pathways that control GluR1 phosphorylation, such as protein kinase A (PKA), protein kinase C, and calcium/calmodulin-dependent protein kinases II (CaMKII), were sulfhydrated, activated by NaHS, and these effects can be occluded by DTT. H2 S increased S-sulfhydration of protein phosphatase type 2A (PP2A), which may be partially involved in the activation of signal pathways. CONCLUSION: Our data suggest that H2 S promotes surface insertion of AMPARs via phosphorylation of GluR1, which depends on a sulfhydration-mediated mechanism. PMID- 27380892 TI - Antibody-Dependent Enhancement of Dengue Virus Infection in Primary Human Macrophages; Balancing Higher Fusion against Antiviral Responses. AB - The dogma is that the human immune system protects us against pathogens. Yet, several viruses, like dengue virus, antagonize the hosts' antibodies to enhance their viral load and disease severity; a phenomenon called antibody-dependent enhancement of infection. This study offers novel insights in the molecular mechanism of antibody-mediated enhancement (ADE) of dengue virus infection in primary human macrophages. No differences were observed in the number of bound and internalized DENV particles following infection in the absence and presence of enhancing concentrations of antibodies. Yet, we did find an increase in membrane fusion activity during ADE of DENV infection. The higher fusion activity is coupled to a low antiviral response early in infection and subsequently a higher infection efficiency. Apparently, subtle enhancements early in the viral life cycle cascades into strong effects on infection, virus production and immune response. Importantly, and in contrast to other studies, the antibody-opsonized virus particles do not trigger immune suppression and remain sensitive to interferon. Additionally, this study gives insight in how human macrophages interact and respond to viral infections and the tight regulation thereof under various conditions of infection. PMID- 27380895 TI - Pronounced genetic differentiation and recent secondary contact in the mangrove tree Lumnitzera racemosa revealed by population genomic analyses. AB - Systematically investigating the impacts of Pleistocene sea-level fluctuations on mangrove plants may provide a better understanding of their demographic history and useful information for their conservation. Therefore, we conducted population genomic analyses of 88 nuclear genes to explore the population dynamics of a mangrove tree Lumnitzera racemosa across the Indo-West Pacific region. Our results revealed pronounced genetic differentiation in this species between the populations from the Indian Ocean and the Pacific Ocean, which may be attributable to the long-term isolation between the western and eastern coasts of the Malay Peninsula during sea-level drops in the Pleistocene glacial periods. The mixing of haplotypes from the two highly divergent groups was identified in a Cambodian population at almost all 88 nuclear genes, suggesting genetic admixture of the two lineages at the boundary region. Similar genetic admixture was also found in other populations from Southeast Asia based on the Bayesian clustering analysis of six nuclear genes, which suggests extensive and recent secondary contact of the two divergent lineages in Southeast Asia. Computer simulations indicated substantial migration from the Indian Ocean towards the South China Sea, which likely results in the genetic admixture in Southeast Asia. PMID- 27380894 TI - MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta. AB - Osteogenesis imperfecta (OI) is a collagen-related bone dysplasia. We identified an X-linked recessive form of OI caused by defects in MBTPS2, which encodes site 2 metalloprotease (S2P). MBTPS2 missense mutations in two independent kindreds with moderate/severe OI cause substitutions at highly conserved S2P residues. Mutant S2P has normal stability, but impaired functioning in regulated intramembrane proteolysis (RIP) of OASIS, ATF6 and SREBP transcription factors, consistent with decreased proband secretion of type I collagen. Further, hydroxylation of the collagen lysine residue (K87) critical for crosslinking is reduced in proband bone tissue, consistent with decreased lysyl hydroxylase 1 in proband osteoblasts. Reduced collagen crosslinks presumptively undermine bone strength. Also, proband osteoblasts have broadly defective differentiation. These mutations provide evidence that RIP plays a fundamental role in normal bone development. PMID- 27380896 TI - Definition of a Skp2-c-Myc Pathway to Expand Human Beta-cells. AB - Type 2 diabetes (T2D) is characterized by insulin resistance and reduced functional beta-cell mass. Developmental differences, failure of adaptive expansion and loss of beta-cells via beta-cell death or de-differentiation have emerged as the possible causes of this reduced beta-cell mass. We hypothesized that the proliferative response to mitogens of human beta-cells from T2D donors is reduced, and that this might contribute to the development and progression of T2D. Here, we demonstrate that the proliferative response of human beta-cells from T2D donors in response to cdk6 and cyclin D3 is indeed dramatically impaired. We show that this is accompanied by increased nuclear abundance of the cell cycle inhibitor, p27(kip1). Increasing nuclear abundance of p27(kip1) by adenoviral delivery decreases the proliferative response of beta-cells from non diabetic donors, mimicking T2D beta-cells. However, while both p27(kip1) gene silencing and downregulation by Skp2 overexpression increased similarly the proliferative response of human beta-cells, only Skp2 was capable of inducing a significant human beta-cell expansion. Skp2 was also able to double the proliferative response of T2D beta-cells. These studies define c-Myc as a central Skp2 target for the induction of cell cycle entry, expansion and regeneration of human T2D beta-cells. PMID- 27380897 TI - Radical Chemistry and Cytotoxicity of Bioreductive 3-Substituted Quinoxaline Di-N Oxides. AB - The radical chemistry and cytotoxicity of a series of quinoxaline di-N-oxide (QDO) compounds has been investigated to explore the mechanism of action of this class of bioreductive drugs. A series of water-soluble 3-trifluoromethyl (4-10), 3-phenyl (11-19), and 3-methyl (20-21) substituted QDO compounds were designed to span a range of electron affinities consistent with bioreduction. The stoichiometry of loss of QDOs by steady-state radiolysis of anaerobic aqueous formate buffer indicated that one-electron reduction of QDOs generates radicals able to initiate chain reactions by oxidation of formate. The 3-trifluoromethyl analogues exhibited long chain reactions consistent with the release of the HO(*), as identified in EPR spin trapping experiments. Several carbon-centered radical intermediates, produced by anaerobic incubation of the QDO compounds with N-terminal truncated cytochrome P450 reductase (POR), were characterized using N tert-butyl-alpha-phenylnitrone (PBN) and 5-(diethoxyphosphoryl)-5-methyl-1 pyrroline-N-oxide (DEPMPO) spin traps and were observed by EPR. Experimental data were well simulated for the production of strongly oxidizing radicals, capable of H atom abstraction from methyl groups. The kinetics of formation and decay of the radicals produced following one-electron reduction of the parent compounds, both in oxic and anoxic solutions, were determined using pulse radiolysis. Back oxidation of the initially formed radical anions by molecular oxygen did not compete effectively with the breakdown of the radical anions to form oxidizing radicals. The QDO compounds displayed low hypoxic selectivity when tested against oxic and hypoxic cancer cell lines in vitro. The results from this study form a kinetic description and explanation of the low hypoxia-selective cytotoxicity of QDOs against cancer cells compared to the related benzotriazine 1,4-dioxide (BTO) class of compounds. PMID- 27380898 TI - The Effects of Shock from Defibrillation Threshold Testing on Cardiac Systolic and Diastolic Function. AB - BACKGROUND: Inappropriate implantable cardioverter defibrillator (ICD) shocks are associated with increased overall mortality. However, it remains unclear whether shocks from defibrillation threshold (DFT) testing directly impair cardiac function. METHODS: DFT testing was performed in 34 patients who underwent ICD/cardiac resynchronization therapy with a defibrillator implantation/generator exchange. Heart rate and cardiac function, including left ventricular (LV) systolic pressure, LV end-diastolic pressure, peak positive and negative dp/dt ( + dp/dt and -dp/dt, respectively) of LV pressure, and the tau index, were assessed with a Mikro-CathTM diagnostic pressure catheter (CD Leycom, Zoetermeer, the Netherlands). These parameters were measured before and 1 minute, 3 minutes, 5 minutes, 10 minutes, and 15 minutes after DFT testing. RESULTS: Peak positive dp/dt increased over baseline at each interval (976 +/- 229 mm Hg/s vs 1,039 +/- 258, 1,049 +/- 245, 1,042 +/- 247, 1,037 +/- 259, and 1,034 +/- 254 mm Hg/s, respectively; P < 0.01). Furthermore, peak negative dp/dt (-1,140 +/- 397 mm Hg/s vs -1,185 +/- 447, 1,193 +/- 435, -1,195 +/- 434, -1,189 +/- 449, and -1,186 +/- 459 mm Hg/s, respectively; P < 0.01) and the tau index (65.1 +/- 18.5 vs 62.5 +/- 16.8*, 62.4 +/- 15.9(**) , 63.0 +/- 16.8*, and 62.8 +/- 18.7*, respectively; *P < 0.05, (**) P < 0.01) decreased compared to those at baseline at each interval. CONCLUSION: Shock after DFT testing improved LV systolic and diastolic function immediately, especially in patients with preserved LV ejection fraction. PMID- 27380899 TI - The surgical workforce shortage and successes in retaining surgical trainees in Ethiopia: a professional survey. AB - BACKGROUND: Medical workforce shortages represent a major challenge in low- and middle-income countries, including those in Africa. Despite this, there is a dearth of information regarding the location and practice of African surgeons following completion of their training. In response to the call by the WHO Global Code of Practice on the International Recruitment of Health Personnel for a sound evidence base regarding patterns of practice and migration of the health workforce, this study describes the current place of residence, practice and setting of Ethiopian surgical residency graduates since commencement of their surgical training in Ethiopia or in Cuba. METHODS: This study presents data from a survey of all Ethiopian surgical residency training graduates since the programme's inception in 1985. RESULTS: A total of 348 Ethiopians had undergone surgical training in Ethiopia or Cuba since 1985; data for 327 (94.0 %) of these surgeons were collected and included in the study. The findings indicated that 75.8 % of graduates continued to practice in Ethiopia, with 80.9 % of these practicing in the public sector. Additionally, recent graduates were more likely to remain in Ethiopia and work within the public sector. The average total number of surgeons per million inhabitants in Ethiopia was approximately three and 48.0 % of Ethiopian surgeons practiced in Addis Ababa. CONCLUSIONS: Ethiopian surgeons are increasingly likely to remain in Ethiopia and to practice in the public sector. Nevertheless, Ethiopia continues to suffer from a drastic surgical workforce shortage that must be addressed through increased training capacity and strategies to combat emigration and attrition. PMID- 27380900 TI - Immobilization of an artificial imine reductase within silica nanoparticles improves its performance. AB - Silica nanoparticles equipped with an artificial imine reductase display remarkable activity towards cyclic imine- and NAD(+) reduction. The method, based on immobilization and protection of streptavidin on silica nanoparticles, shields the biotinylated metal cofactor against deactivation yielding over 46 000 turnovers in pure samples and 4000 turnovers in crude cellular extracts. PMID- 27380901 TI - Reducing avoidable admissions in rural community palliative care: a pilot study of care coordination by General Practice registrars. AB - OBJECTIVE: To investigate the feasibility of using a General Practice registrar (GPR) to coordinate rural palliative care services. DESIGN: A quasi-experimental design was used. Intervention group participants received the GPR service, which involved liaison among the patient, family, General Practitioner, specialist palliative care team and community nurses. Specified risk assessment, care planning and continuity of care were provided. Patients in the comparison group received the standard service. SETTING: Rural community palliative care. PARTICIPANTS: One hundred and ninety-one rural community palliative care patients (99 intervention and 92 control patients). MAIN OUTCOME MEASURES: Hospital admissions per 100 patient-days, bed-days per 100 patient-days and proportion of deaths at home. RESULTS: Patients receiving standard care were twice as likely to spend >=8 bed-days in hospital (OR 2.09 (95%CI 1.10-3.97); P = 0.02) and were more likely to have >= 2 admissions to hospital (OR 3.37 (95%CI 1.83-6.21); P < 0.001), per 100 patient-days than the intervention group after adjusting for diagnosis group (cancer or not) and residence in residential aged care. Controls were significantly less likely to die at home than the intervention group (OR 0.41 (95%CI 0.20-0.86); P = 0.02). CONCLUSION: This is a small proof of concept pilot study limited by lack of randomisation. The results demonstrate the feasibility of using a GPR to manage continuity of care for rural community palliative care patients. Given the potential confounding factors, further investigation via a larger randomised trial is required. PMID- 27380902 TI - CT-based texture analysis potentially provides prognostic information complementary to interim fdg-pet for patients with hodgkin's and aggressive non hodgkin's lymphomas. AB - OBJECTIVES: The purpose of this study was to investigate the ability of computed tomography texture analysis (CTTA) to provide additional prognostic information in patients with Hodgkin's lymphoma (HL) and high-grade non-Hodgkin's lymphoma (NHL). METHODS: This retrospective, pilot-study approved by the IRB comprised 45 lymphoma patients undergoing routine 18F-FDG-PET-CT. Progression-free survival (PFS) was determined from clinical follow-up (mean-duration: 40 months; range: 10 62 months). Non-contrast-enhanced low-dose CT images were submitted to CTTA comprising image filtration to highlight features of different sizes followed by histogram-analysis using kurtosis. Prognostic value of CTTA was compared to PET FDG-uptake value, tumour-stage, tumour-bulk, lymphoma-type, treatment-regime, and interim FDG-PET (iPET) status using Kaplan-Meier analysis. Cox regression analysis determined the independence of significantly prognostic imaging and clinical features. RESULTS: A total of 27 patients had aggressive NHL and 18 had HL. Mean PFS was 48.5 months. There was no significant difference in pre treatment CTTA between the lymphoma sub-types. Kaplan-Meier analysis found pre treatment CTTA (medium feature scale, p=0.010) and iPET status (p<0.001) to be significant predictors of PFS. Cox analysis revealed that an interaction between pre-treatment CTTA and iPET status was the only independent predictor of PFS (HR: 25.5, 95% CI: 5.4-120, p<0.001). Specifically, pre-treatment CTTA risk stratified patients with negative iPET. CONCLUSION: CTTA can potentially provide prognostic information complementary to iPET for patients with HL and aggressive NHL. KEY POINTS: * CT texture-analysis (CTTA) provides prognostic information complementary to interim FDG-PET in Lymphoma. * Pre-treatment CTTA and interim PET status were significant predictors of progression-free survival. * Patients with negative interim PET could be further stratified by pre-treatment CTTA. * Provide precision surveillance where additional imaging reserved for patients at greatest recurrence-risk. * Assists in risk-adapted treatment strategy based on interim PET and CTTA. PMID- 27380903 TI - Reliability of MRI assessment of acute musculotendinous groin injuries in athletes. AB - OBJECTIVES: To describe a multi-dimensional MRI assessment approach with a focus on acute musculotendinous groin lesions, and to evaluate scoring reproducibility. METHODS: Male athletes who participated in competitive sports and presented within 7 days of an acute onset of sports-related groin pain were included. All athletes underwent MRI (1.5 T) according to a standardized groin-centred protocol. From several calibration sessions, a system was developed assessing grade, location and extent of muscle strains, peri-lesional haematoma, as well as other non-acute findings commonly associated with long-standing groin pain. Kappa (K) statistics and intraclass correlation coefficients (ICCs) were used to describe intra- and inter-rater reproducibility. RESULTS: Seventy-five athletes (mean age 26.6 +/- 4.4 years) were included in the analyses, and 85 different acute lesions were observed. Adductor longus lesions were most common (42.7 %) followed by rectus femoris lesions (16.3 %). Kappa values ranged between 0.70 and 1.00 for almost all categorical features for acute lesions, with almost perfect intra- and inter-rater agreement (K = 0.89-1.00) for presence, number, location and grading of lesions. ICCs ranged between 0.77 and 1.00 for continuous measures of acute lesion extent. CONCLUSIONS: A standardized MRI assessment approach of acute groin injuries was described and showed good intra- and inter-rater reproducibility. KEY POINTS: * A multidimensional MRI assessment approach for acute groin injuries was described. * Standardized MRI assessment of acute musculotendinous groin injuries has high reproducibility. * Injury location and injury extent can be scored reliably using 1.5 T MRI. PMID- 27380904 TI - Noninvasive detection of coronary vasospastic angina using a double-acquisition coronary CT angiography protocol in the presence and absence of an intravenous nitrate: a pilot study. AB - OBJECTIVES: To evaluate the feasibility of a double-acquisition coronary CT angiography (CCTA) protocol in the presence and absence of an intravenous (IV) vasodilator infusion for detecting vasospastic angina. METHODS: Twenty patients with a high clinical probability of vasospastic angina were enrolled. All subjects underwent baseline CCTA without a vasodilator in the early morning followed by a catheterized coronary angiography with ergonovine provocation test. Within 3 days, all subjects underwent repeat CCTA during a continuous IV infusion of nitrate. Vasospastic angina as detected by CCTA was defined as significant stenosis (>=50 %) with negative remodelling without definite plaques or diffuse small diameter (<2 mm) of a major coronary artery with a beaded appearance on baseline CT that completely dilated on IV nitrate CT. The CCTA results were compared to the catheterized ergonovine provocation test as the reference standard. RESULTS: Among 20 patients, the catheterized ergonovine provocation test detected vasospasm in 15 patients. The sensitivity, specificity, positive predictive value and negative predictive value of CCTA in a per-patient-based analysis were 73, 100, 100 and 56 %, respectively. CONCLUSIONS: Double acquisition CCTA in the presence and absence of IV infusion of nitrate allows noninvasive detection of vasospastic angina with moderate sensitivity and high specificity. KEY POINTS: * Limited data exist regarding the efficacy of CCTA in detecting vasospastic angina. * We propose a double-acquisition CCTA protocol with and without IV nitrate injections. * This protocol provides 100% specificity and moderate sensitivity (73%) in spasm detection. PMID- 27380906 TI - Double benefit of long-acting somatostatin analogs in a patient with coexistence of acromegaly and ulcerative colitis. AB - WHAT IS KNOWN AND OBJECTIVE: Somatostatin analogs control GH/IGF-1 excess in acromegaly. Somatostatin receptors also mediate the complex effects of somatostatin on the gastrointestinal tract and may be defensive in inflammatory bowel diseases, such as ulcerative colitis. We present a patient who showed good response to long-acting octreotide (OCT-LAR) treatment in terms of both acromegaly and ulcerative colitis (UC). CASE SUMMARY: A 58-year-old female patient with diagnosis of acromegaly and ulcerative colitis was started on long acting somatostatin treatment as a first-line treatment for acromegaly as she refused to undergo transsphenoidal surgery. During the follow-up period, a significant amelioration was also observed in the course of ulcerative colitis, and clinical remission of both diseases was achieved uneventfully. WHAT IS NEW AND CONCLUSION: Somatostatin appears to be a promising candidate in the treatment of inflammatory bowel diseases. PMID- 27380905 TI - Characterizing amide proton transfer imaging in haemorrhage brain lesions using 3T MRI. AB - OBJECTIVES: The aim of this study was to characterize amide proton transfer (APT) weighted signals in acute and subacute haemorrhage brain lesions of various underlying aetiologies. METHODS: Twenty-three patients with symptomatic haemorrhage brain lesions including tumorous (n = 16) and non-tumorous lesions (n = 7) were evaluated. APT imaging was performed and analyzed with magnetization transfer ratio asymmetry (MTR asym ). Regions of interest were defined as the enhancing portion (when present), acute or subacute haemorrhage, and normal appearing white matter based on anatomical MRI. MTR asym values were compared among groups and components using a linear mixed model. RESULTS: MTR asym values were 3.68 % in acute haemorrhage, 1.6 % in subacute haemorrhage, 2.65 % in the enhancing portion, and 0.38 % in normal white matter. According to the linear mixed model, the distribution of MTR asym values among components was not significantly different between tumour and non-tumour groups. MTR asym in acute haemorrhage was significantly higher than those in the other regions regardless of underlying pathology. CONCLUSIONS: Acute haemorrhages showed high MTR asym regardless of the underlying pathology, whereas subacute haemorrhages showed lower MTR asym than acute haemorrhages. These results can aid in the interpretation of APT imaging in haemorrhage brain lesions. KEY POINTS: * Acute haemorrhages show significantly higher MTR asym values than subacute haemorrhages. * MTR asym is higher in acute haemorrhage than in enhancing tumour tissue. * MTR asym in haemorrhage does not differ between tumorous and non tumorous lesions. PMID- 27380907 TI - Reclassification of Alteromonas fuliginea (Romanenko et al. 1995) as Pseudoalteromonas fuliginea comb. nov. and an emended description. AB - A new aerobic marine bacterium, strain S3431, was isolated from swab samples of an unidentified polychaete near Canal Concepcion, Chile. This strain was thought to represent a new taxon within the genus Pseudoalteromonas. Although DNA-DNA reassociation values showed less than 70 % genomic DNA relatedness to established Pseudoalteromonas type strains, it shared 78 % DNA-DNA relatedness with Alteromonas fuliginea DSM 15748 (=KMM 216) (Romanenko et al., 1994). A. fuliginea has later been considered a heterotypic synonym of Pseudoalteromonas citrea(Ivanova et al., 1998). Relatedness between strains S3431, A. fuliginea DSM 15748 and the type strain P. citrea LMG 12323T was therefore studied. Physiological traits and genomic information were shared at a high level by strains S3431 and DSM 15748, but not between these and P. citrea LMG 12323T. There was only approximately 20 % DNA-DNA relatedness between P. citrea LMG 12323T and strains S3431 and DSM 15748. Based on the available phylogenetic and phenotypic data, the reclassification of A. fuliginea DSM 15748 (Romanenko et al., 1995) -> Pseudoalteromonas citrea(Ivanova et al., 1998) as Pseudoalteromonas fuligineacomb. nov. is proposed, and strain S3431 should be assigned to this new species. The name Pseudoalteromonas fuliginea is proposed with KMM 216T (=DSM 15748T=CIP 105339T) as the type strain. PMID- 27380908 TI - Single-cell genome-wide bisulfite sequencing uncovers extensive heterogeneity in the mouse liver methylome. AB - BACKGROUND: Transmission fidelity of CpG DNA methylation patterns is not foolproof, with error rates from less than 1 to well over 10 % per CpG site, dependent on preservation of the methylated or unmethylated state and the type of sequence. This suggests a fairly high chance of errors. However, the consequences of such errors in terms of cell-to-cell variation have never been demonstrated by experimentally measuring intra-tissue heterogeneity in an adult organism. RESULTS: We employ single-cell DNA methylomics to analyze heterogeneity of genome wide 5-methylcytosine (5mC) patterns within mouse liver. Our results indicate a surprisingly high level of heterogeneity, corresponding to an average epivariation frequency of approximately 3.3 %, with regions containing H3K4me1 being the most variable and promoters and CpG islands the most stable. Our data also indicate that the level of 5mC heterogeneity is dependent on genomic features. We find that non-functional sites such as repeat elements and introns are mostly unstable and potentially functional sites such as gene promoters are mostly stable. CONCLUSIONS: By employing a protocol for whole-genome bisulfite sequencing of single cells, we show that the liver epigenome is highly unstable with an epivariation frequency in DNA methylation patterns of at least two orders of magnitude higher than somatic mutation frequencies. PMID- 27380909 TI - Early childhood obesity: Association with healthcare expenditure in Australia. AB - OBJECTIVE: To determine whether overweight or obesity among children (aged 2 to <=5 years) is associated with direct healthcare costs, after adjusting for child, household, and socioeconomic characteristics. METHODS: A longitudinal cohort analysis was performed in 350 children aged 2 years assessed over 3 years of follow-up. Child weight status was determined from mean BMI z-scores at 2, 3.5, and 5 years, and healthcare utilization including medicines, nonhospital, hospital, and emergency care was determined by data linkage. Using adjusted multivariable regression analyses, the relationship between total 3-year healthcare costs and weight status was examined. Observations took place in Sydney, Australia, between 2011 and 2014. RESULTS: After adjustment for significant maternal and sociodemographic characteristics, healthcare costs of children with obesity (BMI z-score >2SD) were 1.62 (95% CI 1.12-2.34, P = 0.01) times those of children with healthy weight. However, costs of overweight children were similar to those of healthy weight (P = 0.96). The additional 3 year costs of healthcare for a child with obesity compared with healthy weight were $AUD 825 (95% CI $135-$2,117) for general patients and $AUD 1332 (95% CI $174-$4,280) for concession card holders. CONCLUSIONS: Prevention of obesity in early childhood may have concurrent benefits in reducing healthcare expenditure. PMID- 27380910 TI - Can vitamin D supplementation reduce prostate cancer disparities? PMID- 27380911 TI - New Studies on Knockout Mouse for the SLC20A2 Gene Show Much More Than Brain Calcifications. PMID- 27380913 TI - The practices, challenges and recommendations of South African audiologists regarding managing children with auditory processing disorders. AB - Audiologists managing children with auditory processing disorders (APD) encounter challenges that include conflicting definitions, several classification profiles, problems with differential diagnosis and a lack of standardised guidelines. The heterogeneity of the disorder and its concomitant childhood disorders makes diagnosis difficult. Linguistic and cultural issues are additional challenges faced by South African audiologists. The study aimed to describe the practices, challenges and recommendations of South African audiologists managing children with APD. A quantitative, non-experimental descriptive survey was used to obtain data from 156 audiologists registered with the Health Professions of South Africa. Findings revealed that 67% screened for APD, 42% assessed while 43% provided intervention. A variety of screening and assessment procedures were being administered, with no standard test battery identified. A range of intervention strategies being used are discussed. When the relationship between the number of years of experience and the audiologists' level of preparedness to practice in the field of APD was compared, a statistically significant difference (p = 0.049) was seen in that participants with more than 10 years of experience were more prepared to practice in this area. Those participants having qualified as speech-language therapists and audiologists were significantly more prepared (p = 0.03) to practice than the audiologists who comprised the sample. Challenges experienced by the participants included the lack of linguistically and culturally appropriate screening and assessment tools and limited normative data. Recommendations included reviewing the undergraduate audiology training programmes, reinstituting the South African APD Taskforce, developing linguistically and culturally appropriate normative data, creating awareness among educators and involving them in the multidisciplinary team. PMID- 27380912 TI - Nickel-Catalyzed Cross-Coupling of Redox-Active Esters with Boronic Acids. AB - A transformation analogous in simplicity and functional group tolerance to the venerable Suzuki cross-coupling between alkyl-carboxylic acids and boronic acids is described. This Ni-catalyzed reaction relies upon the activation of alkyl carboxylic acids as their redox-active ester derivatives, specifically N-hydroxy tetrachlorophthalimide (TCNHPI), and proceeds in a practical and scalable fashion. The inexpensive nature of the reaction components (NiCl2 ?6 H2 O-$9.5 mol(-1) , Et3 N) coupled to the virtually unlimited commercial catalog of available starting materials bodes well for its rapid adoption. PMID- 27380914 TI - The effect of age of cochlear implantation on vocal characteristics in children. AB - BACKGROUND: Early cochlear implantation aids auditory feedback and supports better communication and self-monitoring of the voice. The objective of this study was to determine whether the age of cochlear implantation has an impact on vocal development in children implanted before age 4. METHOD AND PROCEDURES: The study consisted of 19 participants in total. All implant recipients (experimental group) were 3-5 years post-implantation, including four prelingual (0-2 years) and five perilingual (2-4 years) implant recipients. The control group consisted of 10 children whose hearing was within normal limits between the ages 3-6 years and 10 months, which was compared to the experimental group. Established paediatric norms were used for additional comparison. A questionnaire was used to gather information from each of the participant's caregivers to determine whether other personal and contextual factors had an impact on voice production. An acoustic analysis was conducted for each participant using the Multi-Dimensional Voice Program of the Computerized Speech Lab. RESULTS: When the experimental group and the control group were compared, similar results were yielded for fundamental frequency and short-term perturbation (jitter and shimmer). More variability was noted in long-term frequency and amplitude measures, with significantly higher differences, and therefore further outside the norms, in the prelingual group when compared to the perilingual and control groups. CONCLUSION: In this study, age of implantation did not impact vocal characteristics. Further research should include larger sample sizes, with participants that are age and gender matched. PMID- 27380915 TI - Halomonas sediminicola sp. nov., a moderately halophilic bacterium isolated from a solar saltern sediment. AB - A Gram-stain-negative, moderately halophilic bacterium, designated strain CPS11T, was isolated from the sediment of a solar pond located in Shinan, Korea. Strain CPS11T was a strictly aerobic, motile, straight rod-shaped bacterium that grew at pH 5.0-9.0 (optimum, pH 7.0-8.0), at 10-37 degrees C (optimum, 28 degrees C) and at salinities of 1-20 % (w/v) NaCl (optimum, 10 % NaCl). Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain CPS11T belonged to the genus Halomonas, with sequence similarity of 98.5-94.3 % to existing type strains, showing highest sequence similarity to Halomonasfontilapidosi 5CRT (98.5 %), Halomonasventosae Al12T (98.5 %), Halomonascampaniensis 5AGT (98.2 %), Halomonas huangheensis BJGMM-B45T (98.0 %), Halomonas alimentaria YKJ-16T (98.0 %), Halomonas mongoliensis Z-7009T (97.8 %), Halomonas shengliensis SL014B-85T (97.5 %) and Halomonas cupida DSM 4740T (97.5 %). The predominant ubiquinone was Q-9. The major fatty acids were C19 : 0 cyclo omega8c, C16 : 1omega7c and/or iso C15 : 0 2-OH, C16 : 0, C17 : 0 cyclo, C12 : 0 3-OH and C18 : 1omega7c. The polar lipids were phosphatidylglycerol, phosphatidylethanolamine, aminophospholipid, an unknown phospholipid and unknown lipids. The DNA G+C content of this novel isolate was 64.3 mol%. Levels of DNA-DNA relatedness between strain CPS11T and the type strains of ten other species of the genus ranged from 50 to 21 %. On the basis of the polyphasic analysis conducted in this study, strain CPS11T represents a novel species of the genus Halomonas, for which the name Halomonas sediminicola sp. nov. is proposed. The type strain is CPS11T(=KACC 18262T=NBRC 110636T). PMID- 27380917 TI - An orthotopic mouse model of small cell lung cancer reflects the clinical course in patients. AB - Small cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer with very poor prognosis due to early metastatic spread and development of chemoresistance. In the last 30 years the study of SCLC has been constrained by a lack of primary human tumor specimen thus highlighting the need of a suitable mouse model. In this article we present the establishment of an orthotopic xenograft mouse model which accurately reproduced the clinical course of SCLC. Orthotopic implantation enabled engraftment of primary lung tumors in all injected mice. Furthermore, immunodeficiency of mice allowed formation of spontaneous metastases in characteristic organs. Bioluminescence Imaging, Magnetic Resonance Imaging and Positron emission tomography were applied to monitor engraftment, metabolism and the exact growth of tumors over time. In order to mimic the extensive disease stage, mice were injected with aggressive human chemoresistant cells leading to development of chemoresistant tumors and early metastatic spread. As a proof of concept treatment of tumor-bearing mice with conventional chemotherapeutics reduced tumor volumes, but a complete regression of tumors was not achieved. By mimicking the extensive disease stage our mouse model can facilitate the study of mechanisms contributing to chemoresistance and metastasis formation, as well as drug screening and evaluation of new treatment strategies for SCLC patients. PMID- 27380918 TI - Systematic reviews of hand hygiene in patient care post 2010. PMID- 27380919 TI - Non-slip socks: a potential reservoir for transmitting multidrug-resistant organisms in hospitals? AB - Non-slip socks are increasingly used to prevent falls in hospitals. Patients use them to walk to various parts of the hospital and also wear them in bed. Fifty four pairs of socks and 35 environmental floor samples were obtained from seven wards in a tertiary referral hospital. Vancomycin-resistant enterococci (VRE) were detected from 46 (85%) socks and meticillin-resistant Staphylococcus aureus (MRSA) from five (9%). Environmental sampling cultured VRE from 24 (69%) floor samples and MRSA from six (17%) floor samples. Clostridium difficile was not detected from any sample. Non-slip socks may become contaminated with multidrug resistant pathogens and may form a potential route for cross-transmission. PMID- 27380916 TI - The current status of checkpoint inhibitors in metastatic bladder cancer. AB - For many decades, no significant improvements could be achieved to prolong the survival in metastatic bladder cancer. Recently, systemic immunotherapy with checkpoint inhibitors (anti-PD-L1/anti-CTLA-4) has been introduced as a novel treatment modality for patients with metastatic bladder cancer. We conducted a systematic review according to the PRISMA statement for data published on the clinical efficacy of checkpoint inhibitors in metastatic bladder cancer. Clinical efficacy of anti PD-L1 therapy was investigated in prospective trials in a total of 155 patients. Patients with positive expression for PD-L1 tended towards better overall response rates (ORR) compared to those with negative expression (34/76 vs 10/73, 45 vs 14 %; p = 0.21). Among patients with PD-L1 positive tumors, those with non-visceral metastases exhibited significantly higher ORR compared to those with visceral metastases (82 vs 28 %; p = 0.001). For anti CTLA4 therapy, there were no data retrievable on clinical efficacy. Although data on clinical efficacy of checkpoint inhibitors in metastatic bladder cancer are currently limited, the efficacy of these drugs might depend mainly on the metastatic volume and immune system integrity. Patients with PD-L1 positive tumors and non-visceral metastases seem to derive the highest benefit from therapy. PMID- 27380920 TI - The effects of cation-anion clustering on defect migration in MgAl2O4. AB - Magnesium aluminate spinel (MgAl2O4), like many other ceramic materials, offers a range of technological applications, from nuclear reactor materials to military body armor. For many of these applications, it is critical to understand both the formation and evolution of lattice defects throughout the lifetime of the material. We use the Speculatively Parallel Temperature Accelerated Dynamics (SpecTAD) method to investigate the effects of di-vacancy and di-interstitial formation on the mobility of the component defects. From long-time trajectories of the state-to-state dynamics, we characterize the migration pathways of defect clusters, and calculate their self-diffusion constants across a range of temperatures. We find that the clustering of Al and O vacancies drastically reduces the mobility of both defects, while the clustering of Mg and O vacancies completely immobilizes them. For interstitials, we find that the clustering of Mg and O defects greatly reduces O interstitial mobility, but has only a weak effect on Mg. These findings illuminate important new details regarding defect kinetics relevant to the application of MgAl2O4 in extreme environments. PMID- 27380921 TI - Potential steps in the evolution of a fused trimeric all-beta dUTPase involve a catalytically competent fused dimeric intermediate. AB - Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is essential for genome integrity. Interestingly, this enzyme from Drosophila virilis has an unusual form, as three monomer repeats are merged with short linker sequences, yielding a fused trimer-like dUTPase fold. Unlike homotrimeric dUTPases that are encoded by a single repeat dut gene copy, the three repeats of the D. virilis dut gene are not identical due to several point mutations. We investigated the potential evolutionary pathway that led to the emergence of this extant fused trimeric dUTPase in D. virilis. The herein proposed scenario involves two sequential gene duplications followed by sequence divergence amongst the dut repeats. This pathway thus requires the existence of a transient two-repeat containing fused dimeric dUTPase intermediate. We identified the corresponding ancestral dUTPase single repeat enzyme together with its tandem repeat evolutionary intermediate and characterized their enzymatic function and structural stability. We additionally engineered and characterized artificial single or tandem repeat constructs from the extant enzyme form to investigate the influence of the emergent residue alterations on the formation of a functional assembly. The observed severely impaired stability and catalytic activity of these latter constructs provide a plausible explanation for evolutionary persistence of the extant fused trimeric D. virilis dUTPase form. For the ancestral homotrimeric and the fused dimeric intermediate forms, we observed strong catalytic and structural competence, verifying viability of the proposed evolutionary pathway. We conclude that the progression along the herein described evolutionary trajectory is determined by the retained potential of the enzyme for its conserved three-fold structural symmetry. PMID- 27380923 TI - Overcoming Barriers to Integrating Behavioral Health and Primary Care Services. AB - OBJECTIVE: Despite barriers, organizations with varying characteristics have achieved full integration of primary care services with providers and services that identify, treat, and manage those with mental health and substance use disorders. What are the key factors and common themes in stories of this success? METHODS: A systematic literature review and snowball sampling technique was used to identify organizations. Site visits and key informant interviews were conducted with 6 organizations that had over time integrated behavioral health and primary care services. Case studies of each organization were independently coded to identify traits common to multiple organizations. RESULTS: Common characteristics include prioritized vulnerable populations, extensive community collaboration, team approaches that included the patient and family, diversified funding streams, and data-driven approaches and practices. CONCLUSIONS: While significant barriers to integrating behavioral health and primary care services exist, case studies of organizations that have successfully overcome these barriers share certain common factors. PMID- 27380924 TI - Embracing the ethically complicated patient. PMID- 27380922 TI - Code for ethical international recruitment practices: the CGFNS alliance case study. AB - Projections indicate a global workforce shortage of approximately 4.3 million across the health professions. The need to ensure an adequate supply of health workers worldwide has created a context for the increased global migration of these professionals. The global trend in the migration of health professionals has given rise to the international recruitment industry to facilitate the passage of health workers from source to destination countries. This is particularly the case in the United States, where the majority of immigrant health professionals have come by way of the recruiting industry. This industry is largely unregulated in the United States as well as in many other countries, for which voluntary codes have been used as a means to increase transparency of the recruitment process, shape professional conduct, and mitigate harm to foreign educated health workers. The CGFNS Alliance case study presented herein describes a multi-stakeholder effort in the United States to promote ethical recruitment practices. Such codes not only complement the WHO Global Code of Practice but are necessary to maximize the impact of these global standards on local settings. This case study offers both a historical perspective and a conceptual framework for examining the multiplicity of factors affecting the migration of human resources for health. The lessons learned provide critical insights into the factors pertaining to the relevancy and effectiveness of the WHO Code from the perspectives of both source and destination countries. This study provides a conceptual model for examining the usefulness of the WHO Code as well as how best to ensure its viability, sustainability, relevancy, and effectiveness in the global environment. This case study concludes with recommendations for evolving business models that need to be in place to strengthen the effectiveness of the WHO Code in the marketplace and to ensure its impact on the international recruitment industry in advancing ethical practices. These recommendations include using effective screening mechanisms to determine health professionals' readiness for migration as well as implementing certification processes to raise the practice standards for those directly involved in recruiting skilled workers and managing the migration flow. PMID- 27380925 TI - Impact of continuity of care on preventable hospitalization and evaluating patient safety indicators between Italy and the USA. PMID- 27380926 TI - Co-expression networks revealed potential core lncRNAs in the triple-negative breast cancer. AB - Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with unfavorable outcome. It is urgent to explore novel biomarkers and potential therapeutic targets in this malignancy. Increasing knowledge of long noncoding RNAs (lncRNAs) significantly deepens our understanding of cancer biology. Here, we sequenced eight paired TNBC tumor tissues and non-cancerous tissues, and validated significantly differentially expressed lncRNAs. Gene ontology (GO) and pathway analysis were used to investigate the function of differentially expressed mRNAs. Further, potential core lncRNAs in TNBC were identified by co expression networks. Kaplan-Meier analysis also indicated that breast cancer patients with lower expression level of rhabdomyosarcoma 2 associated transcript (RMST), one of the potential core lncRNAs, had worse overall survival. To the best of our knowledge, it was the first report that RMST was involved in breast cancer. Our research provided a rich resource to the research community for further investigating lncRNAs functions and identifying lncRNAs with diagnostic and therapeutic potentials in TNBC. PMID- 27380927 TI - NHS leaders condemn racist abuse of staff. PMID- 27380928 TI - Analysis of Triplet Exciton Loss Pathways in PTB7:PC71BM Bulk Heterojunction Solar Cells. AB - A strategy for increasing the conversion efficiency of organic photovoltaics has been to increase the VOC by tuning the energy levels of donor and acceptor components. However, this opens up a new loss pathway from an interfacial charge transfer state to a triplet exciton (TE) state called electron back transfer (EBT), which is detrimental to device performance. To test this hypothesis, we study triplet formation in the high performing PTB7:PC71BM blend system and determine the impact of the morphology-optimizing additive 1,8-diiodoctane (DIO). Using photoluminescence and spin-sensitive optically detected magnetic resonance (ODMR) measurements at low temperature, we find that TEs form on PC71BM via intersystem crossing from singlet excitons and on PTB7 via EBT mechanism. For DIO blends with smaller fullerene domains, an increased density of PTB7 TEs is observed. The EBT process is found to be significant only at very low temperature. At 300 K, no triplets are detected via ODMR, and electrically detected magnetic resonance on optimized solar cells indicates that TEs are only present on the fullerenes. We conclude that in PTB7:PC71BM devices, TE formation via EBT is impacted by fullerene domain size at low temperature, but at room temperature, EBT does not represent a dominant loss pathway. PMID- 27380929 TI - Development of a Spanish-Language Hospice Video. AB - The nation faces a persistent issue of delayed access to hospice care. Even though hospice enrollment is considered to be one of the most difficult medical decisions, physician clinics and hospitals lack tools for helping patients/families faced with making decisions about enrollment. Health-care literature lacks discussion of development of decision-making aids in the context of hospice decisions for minority ethnic groups, even though those groups have decisional needs that may differ from those of non-Hispanic whites. To fill the gap, we developed a video of a Latino hospice patient with footages showing how the patient was being taken care of by her family with support from a hospice disciplinary team. A primary objective of this article is to describe how focus groups, existing decision aids, and individual interviews were used to develop and improve a Spanish-language hospice educational video targeting Latino subgroups with linguistic, cultural, and educational barriers. These steps may provide guidelines for developing and revising health-related videos targeting other minority ethnic groups. PMID- 27380930 TI - Dense red blood cell and oxygen desaturation in sickle-cell disease. AB - Production of abnormal hemoglobin (HbS) in sickle-cell disease (SCD) results in its polymerization in deoxygenated conditions and in sickled-RBC formation. Dense RBCs (DRBCs), defined as density >1.11 and characterized by increased rigidity are absent in normal AA subjects, but present at percentages that vary of a patient to another remaining stable throughout adulthood for each patient. Polymerized HbS has reduced affinity for oxygen, demonstrated by the rightward shift of the oxygen-dissociation curve, leading to disturbances in oxygen transport. Ninety-two SCD patients' total RBCs were separated into LightDRBC (LRBC) (d < 1.11 g/mL) and DRBC fractions. Venous blood partial oxygen pressure and RBC-fraction-deoxygenation and -reoxygenation Hb-oxygen-equilibrium curves were determined. All patients took a 6-minute walking test (6MWT); 10 had results before and after >6 months on hydroxyurea. 6MWT time with SpO2 < 88% (TSpO2 < 88) assessed the physiological impact of exertion. Elevated mean corpuscular hemoglobin (Hb) concentrations, decreased %HbF, and 2,3-bisphosphoglycerates in DRBCs modulated Hb-oxygen affinity. Deoxygenation and reoxygenation Hb-oxygen equilibrium curves differed between normal Hb AA and SS RBCs and between LRBCs and DRBCs, with rightward shifts confirming HbS-polymerization's role in affinity loss. In bivariate analyses, 50% Hb saturation correlated positively with %DRBCs (P < 0.0001, r(2) = 0.34) and negatively with %HbF (P < 0.0001, r(2) = 0.25). The higher the %DRBCs, the longer the TSpO2 88 (P = 0.04). Hydroxyurea was associated with significantly shorter TSpO2 < 88 (P = 0.01). We report that the %DRBCs directly affects SCD patients' SpO2 during exertion; hydroxyurea improves oxygen affinity and lowers the %DRBCs. Am. J. Hematol. 91:1008-1013, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27380931 TI - Psychosocial interventions for people with dementia: An overview and commentary on recent developments. AB - An influential review in 2010 concluded that non-pharmacological multi-component interventions have positive effects on cognitive functioning, activities of daily living, behaviour and mood of people with dementia. Our aim here is to provide an up-to-date overview of research into psychosocial interventions and their impact on psychosocial outcomes. We focused on randomised controlled trials, controlled studies and reviews published between October 2008 and August 2015, since the earlier review. The search of PsychInfo, Medline and the Cochrane database of systematic reviews yielded 61 relevant articles, organised into four themes echoing key phases of the care pathway: Living at home with dementia (five reviews, eight studies), carer interventions (three reviews, four studies), interventions in residential care (16 reviews, 12 studies) and end-of-life care (three reviews, two studies), along with an additional group spanning community and institutional settings (six reviews, two studies). Community findings suggested that appointment of dementia specialists and attention to case management can produce positive outcomes; physical therapies, cognitive training and modified cognitive behaviour therapy also had a range of benefits. There was more limited evidence of positive benefits for people with dementia through interventions with family carers. Thirty-two articles focused on the management of 'behavioural symptoms' through a range of interventions all of which had some evidence of benefit. Also a range of multi-component and specific interventions had benefits for cognitive, emotional and behavioural well-being of people with dementia in residential settings, as well as for quality of life. Overall, interventions tended to be short term with impact only measured in the short term. We recommend further research on interventions to promote living well in the community post-diagnosis and to address end-of-life care. Development of psychosocial interventions would benefit from moving beyond the focus on control of behaviours to focus on wider aspects of life for people with dementia. PMID- 27380932 TI - In vivo transplantation of fetal human gut-derived enteric neural crest cells. AB - The prospect of using neural cell replacement for the treatment of severe enteric neuropathies has seen significant progress in the last decade. The ability to harvest and transplant enteric neural crest cells (ENCCs) that functionally integrate within recipient intestine has recently been confirmed by in vivo murine studies. Although similar cells can be harvested from human fetal and postnatal gut, no studies have as yet verified their functional viability upon in vivo transplantation. We sought to determine whether ENCCs harvested from human fetal bowel are capable of engraftment and functional integration within recipient intestine following in vivo transplantation into postnatal murine colon. Enteric neural crest cells selected and harvested from fetal human gut using the neurotrophin receptor p75NTR were lentivirally labeled with either GFP or calcium-sensitive GCaMP and transplanted into the hindgut of Rag2- /gammac- /C5- -immunodeficient mice at postnatal day 21. Transplanted intestines were assessed immunohistochemically for engraftment and differentiation of donor cells. Functional viability and integration with host neuromusculature was assessed using calcium imaging. Transplanted human fetal gut-derived ENCC showed engraftment within the recipient postnatal colon in 8/15 mice (53.3%). At 4 weeks posttransplantation, donor cells had spread from the site of transplantation and extended projections over distances of 1.2 +/- 0.6 mm (n = 5), and differentiated into enteric nervous system (ENS) appropriate neurons and glia. These cells formed branching networks located with the myenteric plexus. Calcium transients (change in intensity F/F0 = 1.25 +/- 0.03; 15 cells) were recorded in transplanted cells upon stimulation of the recipient endogenous ENS demonstrating their viability and establishment of functional connections. PMID- 27380933 TI - Flower detection and acuity of the Australian native stingless bee Tetragonula carbonaria Sm. AB - We tested the endemic Australian Tetragonula carbonaria bee as a model of how colour vision may allow these small bees to find flowers. In a Y-Maze apparatus, we presented stimuli that contained both chromatic- and green-receptor contrasts, or only had chromatic contrast to free flying bees. Stimuli were detected at visual angles of 9.5 degrees and 9.3 degrees , respectively. We next made morphological measurements of the compound eye under high magnification using a digital microscope, and despite a relatively small eye size with a surface area of 0.64 +/- 0.02 mm(2), the compound eye contained 3010 +/- 10 ommatidia. Measurements of diverging rays of light using antidromic illumination revealed a mean interommatidial angle in the frontal visual field measures 1.56 degrees +/- 0.10 degrees . Finally, we calculate that the minimum number of ommatidia that need to be excited for object detection is 33, which is much higher than for object detection in bumblebees and for the detection of objects providing both colour and green contrasts by honeybees, but lower for the detection of an object lacking green contrast in honeybees. We discuss reasons that may explain potential tradeoff for foraging bees. PMID- 27380935 TI - Active fluidization in dense glassy systems. AB - Dense soft glasses show strong collective caging behavior at sufficiently low temperatures. Using molecular dynamics simulations of a model glass former, we show that the incorporation of activity or self-propulsion, f0, can induce cage breaking and fluidization, resulting in the disappearance of the glassy phase beyond a critical f0. The diffusion coefficient crosses over from being strongly to weakly temperature dependent as f0 is increased. In addition, we demonstrate that activity induces a crossover from a fragile to a strong glass and a tendency of active particles to cluster. Our results are of direct relevance to the collective dynamics of dense active colloidal glasses and to recent experiments on tagged particle diffusion in living cells. PMID- 27380934 TI - Do youth with type 1 diabetes exercise safely? A focus on patient practices and glycemic outcomes. AB - OBJECTIVE: Insulin adjustments have been shown to reduce glycemic excursions during and after exercise, but little is known about their use in youth with type 1 diabetes (T1D). We aimed to assess practices in youth with T1D around exercise, assess factors that influence practices, and examine associations between key behaviors and glycemic outcomes. RESEARCH DESIGN AND METHODS: We developed the 'Type 1 Diabetes Report of Exercise Practices Survey (T1D-REPS)' and piloted this tool in 100 youth with T1D on an insulin pump. Participants completed a 3-day physical activity recall and 30 days of pump/glucose data were collected. Chart review was conducted for key clinical measures. RESULTS: Eighty-four percent of participants modified their insulin regimen around exercise; only 40% reported adjusting prandial insulin immediately before exercise while 68% reported some modification (suspension or decrease) of basal insulin during exercise. Following exercise, only 10% reported reducing overnight basal insulin. Those who performed >= 5 glucose checks/day adjusted basal insulin during exercise more frequently than those with fewer daily glucose checks (33% vs. 13%, p = 0.05, chi-squared = 3.7), and were more likely to report decreasing insulin dose for the bedtime snack following exercise (50% vs. 17%, p = 0.004, chi-squared = 8.2). CONCLUSIONS: Despite several studies showing the frequency of hypoglycemia during and after exercise, many youth are not adjusting insulin for exercise. A tool designed to capture patient practices and provide clinicians with a framework for patient education may lead to improved safety around exercise in youth with T1D. PMID- 27380936 TI - Telomere Visualization in Tissue Sections using Pyrrole-Imidazole Polyamide Probes. AB - Pyrrole-Imidazole (PI) polyamides bind to specific DNA sequences in the minor groove with high affinity. Specific DNA labeling by PI polyamides does not require DNA denaturation with harsh treatments of heat and formamide and has the advantages of rapid and less disruptive processing. Previously, we developed tandem hairpin PI polyamide probes (TH59 series), which label telomeres in cultured cell lines more efficiently than conventional methods, such as fluorescence in situ hybridization (FISH). Here, we demonstrate that a TH59 derivative, HPTH59-b, along with immunostaining for specifying cell types in the tissues, visualizes telomeres in mouse and human tissue sections. Quantitative measurements of telomere length with single-cell resolution suggested shorter telomeres in the proliferating cell fractions of tumor than in non-tumor tissues. Thus, PI polyamides are a promising alternative for telomere labeling in clinical research, as well as in cell biology. PMID- 27380938 TI - Enzymatic extraction and characterisation of a thermostable collagen from swim bladder of rohu (Labeo rohita). AB - BACKGROUND: The fish swim bladder is considered as a potential source of realistic collagen. Currently, processing of the Indian major carp rohu (Labeo rohita) generates an enormous quantity of non-edible by-products, including swim bladders, which are discarded as waste with no commercial value. In the present study, collagen was prepared from rohu swim bladder and its physicochemical and fibril-forming capacities were assessed. RESULTS: The collagen isolated from rohu swim bladder was characterised as type I, containing alpha1 and alpha2 chains with triple helical structure by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, fourier transform infrared spectroscopy and amino acid analysis. The extracted collagen denaturation temperature was found to be 42.16 degrees C by differential scanning calorimetry analysis and also exhibited a high solubility in the presence of low NaCl concentrations (0-0.6 mol L-1 ). The extracted collagen exhibited a high fibril-formation capacity at a NaCl concentration of 1.5 mol L-1 . Examination of the microstructure of collagen by scanning electron microscopy (SEM) showed a porous, sheet-like film and a multilayered structure. The fibril formation capacity of collagen was also confirmed using SEM analysis. CONCLUSION: The rohu swim bladder type I collagen was successfully extracted using an enzymatic method with a yield of 465.2 g kg-1 (dry weight basis) and was characterised as a well maintained triple helical structure. The extracted collagen exhibited a high fibril-forming ability. The results of the present study confirm that utilisation of rohu swim bladder will open up a new avenue for the better disposal of by-products and also help to minimise environmental pollution issues. (c) 2016 Society of Chemical Industry. PMID- 27380937 TI - The Naturally Occurring Compound Garcinia Indica Selectively Impairs the Reconsolidation of a Cocaine-Associated Memory. AB - Sustained abstinence from cocaine use is frequently compromised by exposure to environmental stimuli that have previously been strongly associated with drug taking. Such cues trigger memories of the effects of the drug, leading to craving and potential relapse. Our work has demonstrated that manipulating cocaine-cue memories by destabilizing them through interfering with the reconsolidation process is one potential therapeutic tool by which to prolong abstinence. Here, we examine the use of the naturally occurring amnestic agent garcinol to manipulate an established cocaine-cue memory. Rats underwent 12 days of cocaine self-administration training during which time active lever presses resulted in an i.v. infusion of cocaine that was paired with a light/tone cue. Next rats underwent lever extinction for 8 days followed by light/tone reactivation and a test of cue-induced cocaine-seeking behavior. Systemic injection of garcinol 30 min after reactivation significantly impaired the reconsolidation of the cocaine associated cue memory. Further testing revealed that garcinol had no effect on drug-induced cocaine-seeking, but was capable of blocking the initial conditioned reinforcing properties of the cue and prevents the acquisition of a new response. Additional experiments showed that the effects of garcinol are specific to reactivated memories only, temporally constrained, cue-specific, long-lasting, and persist following extended cocaine access. These data provide strong evidence that the naturally occurring compound, garcinol, may be a potentially useful tool to sustain abstinence from drug abuse. PMID- 27380940 TI - Saturnispora bothae sp. nov., isolated from rotting wood. AB - Two strains representing a novel species of the genus Saturnispora were isolated from rotting wood samples collected in an Atlantic Rainforest site in Brazil. Analyses of the sequences of the D1/D2 domains of the rRNA gene showed that this novel species belongs to a subclade in the Saturnispora clade formed by Saturnispora sanitii, Saturnispora sekii, Saturnispora silvae and Saturnisporasuwanaritii. The novel species differed in D1/D2 sequences by 60 or more nucleotide substitutions from these species. The strains produced asci with one to four hemispherical ascospores. A novel species named Saturnispora bothae sp. nov. is proposed to accommodate these isolates. The type strain is UFMG-CM Y292T (=CBS 13484T). The MycoBank number is MB 817127. PMID- 27380941 TI - Depression in Diabetic Retinopathy: A Review and Recommendation for Psychiatric Management. AB - BACKGROUND: Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and one of the main causes of irreversible vision impairment in the working-age population. Multiple studies have demonstrated the significantly high prevalence of depression in patients with DR in recent years. The progression of DR could lead to depression, whereas depressive symptoms often worsen the condition of DR. Therefore, DR is one of the causes of psychosomatic diseases, the treatment for which should combine traditional DR therapy with depression interventions. METHODS: We reviewed existing articles that investigated the association between DR and depression in the context of prevalence, risk factors, biological mechanisms, and treatment indications. RESULTS: The literature review in this article includes a brief introduction to current studies of depression and DR, followed by a focus on the epidemiology of depression in DR that help doctors better identify potential or existing depression patients upon first diagnosis. The underlying biologic mechanisms between the 2 diseases are briefly reviewed, and potential treatments are addressed. CONCLUSIONS: Depression in patients with DR is not uncommon and has a negative effect on the condition of DR. To achieve optimal prognosis in patients with DR and depression, more attention to combined psychiatric therapies for depression is recommended. PMID- 27380942 TI - Unusually Facile Thermal Homodienyl-[1,5]-Hydrogen Shift Reactions in Photochemically Generated Vinyl Aziridines. AB - A range of photochemically generated tri- and tetracyclic vinyl aziridines have been found to undergo a general and surprisingly low temperature ring opening through a [1,5]-hydrogen shift reaction. The rate of the process was found to be highly dependent on the structure and substitution around the azirdine ring and the alkene terminus, with some substrates being observed to undergo ring opening at temperatures as low as 25 degrees C. The rigid nature of these polycyclic systems precludes a conformational explanation of these rate differences, and an Eyring study confirmed a negligible entropic barrier to the reaction. However, the Eyring plots for two different aziridines systems showed a significant difference in their enthalpies of activation. It is therefore believed that the levels of aziridine ring strain, as well as electronic effects, are the dominant factors in this sequence. PMID- 27380939 TI - Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR. AB - BACKGROUND: The success of the CRISPR/Cas9 genome editing technique depends on the choice of the guide RNA sequence, which is facilitated by various websites. Despite the importance and popularity of these algorithms, it is unclear to which extent their predictions are in agreement with actual measurements. RESULTS: We conduct the first independent evaluation of CRISPR/Cas9 predictions. To this end, we collect data from eight SpCas9 off-target studies and compare them with the sites predicted by popular algorithms. We identify problems in one implementation but found that sequence-based off-target predictions are very reliable, identifying most off-targets with mutation rates superior to 0.1 %, while the number of false positives can be largely reduced with a cutoff on the off-target score. We also evaluate on-target efficiency prediction algorithms against available datasets. The correlation between the predictions and the guide activity varied considerably, especially for zebrafish. Together with novel data from our labs, we find that the optimal on-target efficiency prediction model strongly depends on whether the guide RNA is expressed from a U6 promoter or transcribed in vitro. We further demonstrate that the best predictions can significantly reduce the time spent on guide screening. CONCLUSIONS: To make these guidelines easily accessible to anyone planning a CRISPR genome editing experiment, we built a new website ( http://crispor.org ) that predicts off targets and helps select and clone efficient guide sequences for more than 120 genomes using different Cas9 proteins and the eight efficiency scoring systems evaluated here. PMID- 27380943 TI - A model for gossip-mediated evolution of altruism with various types of false information by speakers and assessment by listeners. AB - Indirect reciprocity is considered to be important for explaining altruism among humans. The evolution of altruism has been modeled using several types of reputational scores, most of which were assumed to be updated immediately after each game session. In this study, we introduce gossip sessions held between game sessions to capture the spread of reputation and examine the effects of false information intentionally introduced by some players. Analytical and individual based simulation results indicated that the frequent exchange of gossip favored the evolution of altruism when no players started false information. In contrast, intermediate repetitions of gossip sessions were favored when the population included liars or biased gossipers. In addition, we found that a gossip listener's strategy of incorporating any gossip regardless of speakers usually worked better than an alternative strategy of not believing gossip from untrustworthy players. PMID- 27380944 TI - Stochastic modelling suggests that an elevated superoxide anion - hydrogen peroxide ratio can drive extravascular phagocyte transmigration by lamellipodium formation. AB - Chemotaxis, integrates diverse intra- and inter-cellular molecular processes into a purposeful patho-physiological response; the operatic rules of which, remain speculative. Here, I surmise, that superoxide anion induced directional motility, in a responding cell, results from a quasi pathway between the stimulus, surrounding interstitium, and its biochemical repertoire. The epochal event in the mounting of an inflammatory response, is the extravascular transmigration of a phagocyte competent cell towards the site of injury, secondary to the development of a lamellipodium. This stochastic-to-markovian process conversion, is initiated by the cytosolic-ROS of the damaged cell, but is maintained by the inverse association of a de novo generated pool of self-sustaining superoxide anions and sub-critical hydrogen peroxide levels. Whilst, the exponential rise of O2(.-) is secondary to the focal accumulation of higher order lipid raft-Rac1/2 actin oligomers; O2(.-) mediated inactivation and redistribution of ECSOD, accounts for the minimal concentration of H2O2 that the phagocyte experiences. The net result of this reciprocal association between ROS/ RNS members, is the prolonged perturbation and remodeling of the cytoskeleton and plasma membrane, a prelude to chemotactic migration. The manuscript also describes the significance of stochastic modeling, in the testing of plausible molecular hypotheses of observable phenomena in complex biological systems. PMID- 27380945 TI - High adult mortality in disease-challenged frog populations increases vulnerability to drought. AB - Pathogen emergence can drive major changes in host population demography, with implications for population dynamics and sensitivity to environmental fluctuations. The amphibian disease chytridiomycosis, caused by infection with the fungal pathogen Batrachochytrium dendrobatidis (Bd), is implicated in the severe decline of over 200 amphibian species. In species that have declined but not become extinct, Bd persists and can cause substantial ongoing mortality. High rates of mortality associated with Bd may drive major changes in host demography, but this process is poorly understood. Here, we compared population age structure of Bd-infected populations, Bd-free populations and museum specimens collected prior to Bd emergence for the endangered Australian frog, Litoria verreauxii alpina (alpine tree frog). We then used population simulations to investigate how pathogen-associated demographic shifts affect the ability of populations to persist in stochastic environments. We found that Bd-infected populations have a severely truncated age structure associated with very high rates of annual adult mortality. Near-complete annual adult turnover in Bd-infected populations means that individuals breed once, compared with Bd-free populations where adults may breed across multiple years. Our simulations showed that truncated age structure erodes the capacity of populations to withstand periodic recruitment failure; a common challenge for species reproducing in uncertain environments. We document previously undescribed demographic shifts associated with a globally emerging pathogen and demonstrate how these shifts alter host ecology. Truncation of age structure associated with Bd effectively reduces host niche width and can help explain the contraction of L. v. alpina to perennial waterbodies where the risk of drought-induced recruitment failure is low. Reduced capacity to tolerate other sources of mortality may explain variation in decline severity among other chytridiomycosis-challenged species and highlights the potential to mitigate disease impacts through minimizing other sources of mortality. PMID- 27380946 TI - Upregulation of Antioxidant Enzymes by ASS234, a Multitarget Directed Propargylamine for Alzheimer's Disease Therapy. PMID- 27380947 TI - Response to letter regarding Embolization is not essential in the treatment of leg varices due to pelvic venous insufficiency. PMID- 27380948 TI - Influx transporter variants as predictors of cancer chemotherapy-induced toxicity: systematic review and meta-analysis. AB - AIM: Chemotherapeutic agents have been shown to increase lung patient survival, however their use may be limited by their serious adverse effects. We aimed to assess int impact of pharmacogenetic variation of influx transporters on inter individual patient variation in adverse drug reactions. PATIENTS & METHODS: We conducted a meta-analysis and systemic review and identified 16 publications, totaling 1510 patients, to be eligible for review. RESULTS: Meta-analysis showed east-Asian patients expressing SLCO1B1 521T>C or 1118G>A to have a two- to fourfold increased risk of irinotecan-induced neutropenia but not diarrhea. American patients, expressing SLC19A1 IVS2(4935) G>A, were further associated with pemetrexed/gemcitabine-induced grade 3+ leukopenia. CONCLUSION: Future studies should look to robust validation of SLCO1B1 and SLC19A1 as prognostic markers in the management of lung cancer patients. PMID- 27380949 TI - Underuse of beta-blockers in heart failure and chronic obstructive pulmonary disease. AB - OBJECTIVE: Although beta-blockers are an established therapy in heart failure (HF) guidelines, including for patients with chronic obstructive pulmonary disease (COPD), there remain concerns regarding bronchoconstriction even with cardioselective beta-blockers. We wished to assess the real-life use of beta blockers for patients with HF and comorbid COPD. METHODS: We evaluated data from the Optimum Patient Care Research Database over a period of 1 year for co prescribing of beta-blockers with either an ACE inhibitor (ACEI) or angiotensin-2 receptor blocker (ARB) in patients with HF alone versus HF+COPD. Association with inhaler therapy was also evaluated. RESULTS: We identified 89 861 patients with COPD, 24 237 with HF and 10 853 with both conditions. In patients with HF+COPD, the mean age was 79 years; 60% were male, and 27% had prior myocardial infarction. Of patients with HF+COPD, 22% were taking a beta-blocker in conjunction with either ACEI/ARB (n=2416) compared with 41% of patients with HF only (n=10 002) (adjusted OR 0.54, 95% CI 0.51 to 0.58, p<0.001). Among HF+COPD patients taking inhaled corticosteroid (ICS) with long-acting beta-agonist (LABA) and long-acting muscarinic antagonist, 27% of patients were taking an ACEI/ARB with beta-blockers (n=778) versus 46% taking an ACEI/ARB without beta-blockers (n=1316). Corresponding figures for those patients taking ICS/LABA were 20% (n=583) versus 48% (n=1367), respectively. CONCLUSIONS: These data indicate a substantial unmet need for patients with COPD who should be prescribed beta blockers more often for concomitant HF. PMID- 27380950 TI - A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL mediated translation arrest. AB - Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-A-resolution cryo-EM structures of ErmBL stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation. PMID- 27380951 TI - Engineered beta-Lactoglobulin Produced in E. coli: Purification, Biophysical and Structural Characterisation. AB - Functional recombinant bovine beta-lactoglobulin has been produced by expression in E. coli using an engineered protein gene and purified to homogeneity by applying a new protocol. Mutations L1A/I2S introduced into the protein sequence greatly facilitate in vivo cleavage of the N-terminal methionine, allowing correctly folded and soluble protein suitable for biochemical, biophysical and structural studies to be obtained. The use of gel filtration on Sephadex G75 at the last purification step enables protein without endogenous ligand to be obtained. The physicochemical properties of recombinant beta-lactoglobulin such as CD spectra, ligand binding (n, K a, DeltaH, TDeltaS, DeltaG), chemical and thermal stability (DeltaG D, C mid) and crystal structure confirmed that the protein obtained is almost identical to the natural one. The substitutions of N terminal residues did not influence the binding properties of the recombinant protein so that the lactoglobulin produced and purified according to our protocol is a good candidate for further engineering and potential use in pharmacology and medicine. PMID- 27380952 TI - Increased calf and plantar muscle fibrotic contents in obese subjects may cause ankle instability. AB - Obesity is strongly associated with musculoskeletal disorders of the lower limb, including ankle instability and resulting gait problems. In the present study, we aimed to examine, using paired comparisons of subjects, whether moderate duration of obesity in patients with mild to moderate elevations of body mass index (BMI), changes the fibrous contents of muscles that support the ankle mortices, namely calf and plantar muscles. We attempted to examine these parameters because this shall provide direct evidence of whether obesity directly impacts myoarchitecture and support of the adjoining joints. MRI image segmentation and pixel correlations by grey level co-occurrence matrix (GLCM) and entropy were used to analyse the changes. The differences in the means between groups (both GLCM and entropy) were significant from control lean populations (P<0.0001, ANOVA) for the parameters examined for both the calf and the plantar muscles. Reduction in weight should thus be a first-line approach in preventing these changes that may significantly affect quality of life due to gait disturbances. PMID- 27380953 TI - Inflammation in low back pain may be detected from the peripheral blood: suggestions for biomarker. AB - Biomarker for prediction of development of low back pain, and disease progression in chronic conditions are virtually non-existent. In the present study, we examined evidence of inflammation in the peripheral blood and demonstrated significant changes in neuroinflammation markers in subjects with chronic low back pain in comparison with control subjects. The present study was performed using peripheral blood from subjects with chronic low back pain and age-matched control subjects. Western blotting, real-time RT-PCR, cell culture and in vitro assays were incorporated to perform the current study. We obtained evidence that the balance between proinflammatory and anti-inflammatory cytokines is misaligned, with decrease in interleukin-10 (IL-10) expression and increase in interleukin-6 (IL-6) expression. Furthermore, we demonstrated increase in CD16 monocyte expression. Cells were cultured under differential conditions to generate M1/M2 macrophages. In the macrophages, opioid secretory capacity was shown to be diminished. Finally, Dragon (repulsive guidance molecule b, RGMb) expression was shown diminished in M1 macrophages, which serves as a key transcriptional inhibitor of IL-6 expression. These biochemical and cellular alterations in chronic low back pain can serve as potential biomarkers for assessing disease initiation, intensity and progression. PMID- 27380954 TI - Rev-erbalpha in the brain is essential for circadian food entrainment. AB - Foraging is costly in terms of time and energy. An endogenous food-entrainable system allows anticipation of predictable changes of food resources in nature. Yet the molecular mechanism that controls food anticipation in mammals remains elusive. Here we report that deletion of the clock component Rev-erbalpha impairs food entrainment in mice. Rev-erbalpha global knockout (GKO) mice subjected to restricted feeding showed reduced elevations of locomotor activity and body temperature prior to mealtime, regardless of the lighting conditions. The failure to properly anticipate food arrival was accompanied by a lack of phase-adjustment to mealtime of the clock protein PERIOD2 in the cerebellum, and by diminished expression of phosphorylated ERK 1/2 (p-ERK) during mealtime in the mediobasal hypothalamus and cerebellum. Furthermore, brain-specific knockout (BKO) mice for Rev-erbalpha display a defective suprachiasmatic clock, as evidenced by blunted daily activity under a light-dark cycle, altered free-running rhythm in constant darkness and impaired clock gene expression. Notably, brain deletion of Rev erbalpha totally prevented food-anticipatory behaviour and thermogenesis. In response to restricted feeding, brain deletion of Rev-erbalpha impaired changes in clock gene expression in the hippocampus and cerebellum, but not in the liver. Our findings indicate that Rev-erbalpha is required for neural network-based prediction of food availability. PMID- 27380956 TI - Laparoscopic Cholecystoduodenostomy in Dogs: Canine Cadaver Feasibility Study. AB - OBJECTIVE: To evaluate the feasibility of laparoscopic cholecystoduodenostomy in canine cadavers using barbed self-locking sutures. STUDY DESIGN: In vivo experimental study. ANIMALS: Fresh male Beagle cadavers (n=5). METHODS: Surgery was performed by a single veterinary surgeon. Dogs were placed in dorsal recumbency and 15 degrees reverse Trendelenburg position. The surgical procedure was performed with four 5 mm entry ports and a 5 mm 30 degrees telescope. The cholecystoduodenostomy technique included dissection, incision of the gallbladder, and lavage, followed by gallbladder transposition over the duodenum, incision of the duodenum, and anastomosis. The latter was performed with a 4-0 barbed self-locking suture (V-Loc(r) 180). Subsequently, a leak test was performed by submerging the anastomosis in saline and insufflating air into the duodenum through a catheter. Total operative time and completion times for each procedural step were recorded. RESULTS: The median total operative time was 151 minutes (range, 129-159). One conversion to open surgery occurred because of vascular hemorrhage. The 3 longest intraoperative steps were posterior wall anastomosis, gallbladder dissection, and anterior wall anastomosis. Intraoperative anastomotic leakage sites were identified in 3 of 5 dogs. Leaks were managed by placement of a single reinforcing conventional intracorporeal suture, which was adequate to obtain a watertight anastomosis. CONCLUSION: This technique cannot be recommended in clinical practice until further studies are performed and the technique is further refined. PMID- 27380955 TI - Multifaceted anti-amyloidogenic and pro-amyloidogenic effects of C-reactive protein and serum amyloid P component in vitro. AB - C-reactive protein (CRP) and serum amyloid P component (SAP), two major classical pentraxins in humans, are soluble pattern recognition molecules that regulate the innate immune system, but their chaperone activities remain poorly understood. Here, we examined their effects on the amyloid fibril formation from Alzheimer's amyloid beta (Abeta) (1-40) and on that from D76N beta2-microglobulin (beta2-m) which is related to hereditary systemic amyloidosis. CRP and SAP dose-dependently and substoichiometrically inhibited both Abeta(1-40) and D76N beta2-m fibril formation in a Ca(2+)-independent manner. CRP and SAP interacted with fresh and aggregated Abeta(1-40) and D76N beta2-m on the fibril-forming pathway. Interestingly, in the presence of Ca(2+), SAP first inhibited, then significantly accelerated D76N beta2-m fibril formation. Electron microscopically, the surface of the D76N beta2-m fibril was coated with pentameric SAP. These data suggest that SAP first exhibits anti-amyloidogenic activity possibly via A face, followed by pro-amyloidogenic activity via B face, proposing a model that the pro- and anti-amyloidogenic activities of SAP are not mutually exclusive, but reflect two sides of the same coin, i.e., the B and A faces, respectively. Finally, SAP inhibits the heat-induced amorphous aggregation of human glutathione S transferase. A possible role of pentraxins to maintain extracellular proteostasis is discussed. PMID- 27380957 TI - Penternary chalcogenides nanocrystals as catalytic materials for efficient counter electrodes in dye-synthesized solar cells. AB - The penternary chalcogenides Cu2CoSn(SeS)4 and Cu2ZnSn(SeS)4 were successfully synthesized by hot-injection method, and employed as a catalytic materials for efficient counter electrodes in dye-synthesized solar cells (DSSCs). The structural, compositional, morphological and optical properties of these pentenary semiconductors were characterized by X-ray diffraction (XRD), Raman spectroscopy, transmission electron microscopy (TEM), energy-dispersive spectrometer (EDS) and ultraviolet-visible (UV-Vis) spectroscopy. The Cu2CoSn(SeS)4 and Cu2ZnSn(SeS)4 nanocrystals had a single crystalline, kesterite phase, adequate stoichiometric ratio, 18-25 nm particle sizes which are forming nanospheres, and band gap energy of 1.18 and 1.45 eV, respectively. Furthermore, the electrochemical impedance spectroscopy and cyclic voltammograms indicated that Cu2CoSn(SeS)4 nanocrystals as counter electrodes exhibited better electrocatalytic activity for the reduction of iodine/iodide electrolyte than that of Cu2ZnSn(SeS)4 nanocrystals and conventional platinum (Pt). The photovoltaic results demonstrated that DSSC with a Cu2CoSn(SeS)4 nanocrystals based counter electrode achieved the best efficiency of 6.47%, which is higher than the same photoanode employing a Cu2ZnSn(SeS)4 nanocrystals (3.18%) and Pt (5.41%) counter electrodes. These promising results highlight the potential application of penternary chalcogen Cu2CoSn(SeS)4 nanocrystals in low-cost, high efficiency, Pt-free DSSCs. PMID- 27380958 TI - The promise of immunotherapy in head and neck squamous cell carcinoma. AB - Squamous cell cancers of the head and neck (HNSCC) comprise a diverse group of malignancies that includes tobacco-related tumors in addition to an increasing number of human papillomavirus-associated cancers. Independently of cause, there is a growing body of evidence supporting that the immune system plays a pivotal role in HNSCC development, as tumor cells evade immunosurveillance by exploiting inhibitory checkpoint pathways that suppress anti-tumor T-cell responses. HNSCC cells have the ability to manipulate the immune system through a variety of different mechanisms, forcing it to promote tumor growth and spread. Over the last decade, discoveries in immunologic research resulted in increased understanding of complex interactions between HNSCC and the host immune system as well as T-cell regulatory mechanisms, promoting the development of a variety of novel immunotherapies. Following the availability of novel immunotherapeutic strategies, the challenge for clinicians is to understand how and in which clinical setting to use these agents in order to provide greater clinical benefit for patients. Combination of immunotherapies with standard treatment approaches also represents an evolving field of research. Herein, we provide a comprehensive review of immune escape mechanisms in HNSCC, as well as current immunotherapy approaches under investigation. PMID- 27380960 TI - Safety and efficacy of autologous serum eye drop for treatment of dry eyes in graft-versus-host disease. AB - PURPOSE: To evaluate the treatment of autologous serum eye drops (ASED) on dry eyes in patients with graft-versus-host disease (GVHD). METHODS: A retrospective chart review of 35 patients with a history of ocular GVHD following hematopoietic stem cell transplantation that used ASED to alleviate dry eye symptoms was performed. Patients were categorized into three different groups. If patients had available ophthalmic data before and after starting treatment was group 1 (n = 14), had available ophthalmic data after starting treatment in group 2 (n = 10) and had available ophthalmic data before treatment or did not have any data after starting treatment in group 3 (n = 11). Data were collected on patient's age, gender, primary diagnosis, visual acuity and fluorescein corneal staining were collected on individual eyes in order to evaluate the efficacy of the ASED on alleviating dry eye-related signs and symptoms. RESULTS: No adverse ocular effect from the ASED was found in our series (except one fungal keratitis). All patients reported either improvement (55%) or stability (45%) in their ocular symptoms upon the use of ASED. In patients with available data before and after starting treatment, the corneal staining score improved by a median of 1 (p = 0.003) and the LogMAR visual acuity had a non-significant improvement. CONCLUSION: In our study, ASED used by patients with ocular GVHD were both safe and effective. ASED should be considered in patients with GVHD who suffer from dry eyes. PMID- 27380959 TI - ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. AB - Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team environment and specialist cancer centres, and the emergence over the same time period not only of improved imaging techniques but also prognostic and predictive molecular markers. Treatment decisions for patients with mCRC must be evidence-based. Thus, these ESMO consensus guidelines have been developed based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting. PMID- 27380961 TI - Dynamics of the heart rate variability and oxygen saturation response to acute normobaric hypoxia within the first 10 min of exposure. AB - Although the heart rate variability (HRV) response to hypoxia has been studied, little is known about the dynamics of HRV after hypoxia exposure. The purpose of this study was to assess the HRV and oxygen saturation (SpO2 ) responses to normobaric hypoxia (FiO2 = 9.6%) comparing 1 min segments to baseline (normoxia). Electrocardiogram and SpO2 were recorded during a 10-min hypoxia exposure in 29 healthy male subjects aged 26.0 +/- 4.9 years. Baseline HRV values were obtained from a 5-min recording period prior to hypoxia. The hypoxia period was split into 10 non-overlapping 1-min segments and time domain HRV indexes (RMSSD and SDNN) were calculated for each segment. Differences (Delta) from baseline values were calculated and transformed using natural logarithm (Ln). This study revealed that the decrease in DeltaSpO2 became significant (P<0.001) in the first minute of hypoxia, the decrease in DeltaLn RMSSD became significant (P = 0.002) in the second minute, and the decrease in DeltaLn SDNN became significant (P = 0.001) in the third minute. Between the second and fifth minute of hypoxia, DeltaSpO2 correlated with DeltaLn RMSSD (r = 0.57, P<0.001) and DeltaLn SDNN (r = 0.44, P<0.001). Five min after the onset of hypoxia, DeltaSpO2 was significantly (P = 0.002) decreased but changes in DeltaLn RMSSD (P = 0.344) and DeltaLn SDNN (P = 0.558) were not significant. In conclusion, the decrease in HRV was proportional to desaturation but only during the first 5 min of hypoxia. PMID- 27380962 TI - Development of a multiplex PCR assay for rapid virulence factor profiling of extraintestinal pathogenic Escherichia coli isolated from cattle. AB - Virulence factor (VF) profiling is important for the control of extraintestinal pathogenic Escherichia coli (ExPEC) infection because VF prevalence is highly variable. We analyzed the VF profile of ExPEC isolated from cattle in Yamagata prefecture, Japan, 2000-2015 and developed a rapid VF profiling method using a multiplex PCR assay. PMID- 27380963 TI - Different binarization processes validated against manual counts of fluorescent bacterial cells. AB - State of the art software methods (such as fixed value approaches or statistical approaches) to create a binary image of fluorescent bacterial cells are not as accurate and precise as they should be for counting bacteria and measuring their area. To overcome these bottlenecks, we introduce biological significance to obtain a binary image from a greyscale microscopic image. Using our biological significance approach we are able to automatically count about the same number of cells as an individual researcher would do by manual/visual counting. Using the fixed value or statistical approach to obtain a binary image leads to about 20% less cells in automatic counting. In our procedure we included the area measurements of the bacterial cells to determine the right parameters for background subtraction and threshold values. In an iterative process the threshold and background subtraction values were incremented until the number of particles smaller than a typical bacterial cell is less than the number of bacterial cells with a certain area. This research also shows that every image has a specific threshold with respect to the optical system, magnification and staining procedure as well as the exposure time. The biological significance approach shows that automatic counting can be performed with the same accuracy, precision and reproducibility as manual counting. The same approach can be used to count bacterial cells using different optical systems (Leica, Olympus and Navitar), magnification factors (200* and 400*), staining procedures (DNA (Propidium Iodide) and RNA (FISH)) and substrates (polycarbonate filter or glass). PMID- 27380964 TI - Paenibacillus silagei sp. nov. isolated from corn silage. AB - A Gram-stain-negative, rod-shaped, endospore-forming bacterium, strain LOOC204T, was isolated from corn silage that had been prepared and stored in Hokkaido, Japan. The isolate grew well at 4-37 degrees C and at pH 6.0-8.5. The major cellular fatty acids were anteiso-C15 : 0, C16 : 0, iso-C14 : 0 and iso-C16 : 0. The major menaquinone was MK-7. Diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, three unidentified aminophospholipids, one unidentified phospholipid, two unidentified aminolipids and three unidentified lipids were detected as the cellular polar lipids. The genomic DNA G+C content of LOOC204T was 52.2+/-0.7 mol%. A comparative 16S rRNA gene sequence analysis showed that LOOC204T represented a member of the genus Paenibacillus, and high levels of sequence similarity of LOOC204T with Paenibacillus borealis KK19T (97.5 %) and Paenibacillusjilunlii Be17T (97.4 %) were found. Based on sequence analysis of the RNA polymerase beta subunit (rpoB) gene, LOOC204T was clearly separated from its phylogenetic neighbors in the genus Paenibacillus. DNA-DNA hybridisation experiments showed that LOOC204T displayed less than 40 % reassociation values toward its nearest phylogenetic neighbours of the genus Paenibacillus, indicating the unique taxonomic status of LOOC204T. Based on these data, we conclude that strain LOOC204T represents a novel species of the genus Paenibacillus, named Paenibacillus silageisp. nov. The type strain is LOOC204T (=JCM 30974T=DSM 101953T). PMID- 27380965 TI - Examining impacts of ceranib-2 on the proliferation, morphology and ultrastructure of human breast cancer cells. AB - Acid ceramidases are enzymes with a vital role in metabolizing ceramide to sphingosine-1-phosphate that is an antiproliferative metabolite in the ceramide pathway. Inhibition of exogenous ceramides with ceramidase inhibitors lead to augmented ceramide levels in cells and in turn lead to cell cycle arrest and apoptosis. Our study aimed at targeting ceramide metabolic pathway to induce apoptosis in human breast cancer cell line (MCF7) and we examined the antiproliferative and apoptotic activities of ceranib-2, an inhibitor of human ceramidase, on this cell line as well ultrastructural and mophological changes. Methods used for our examinations in this study were the colorimetric MTT assay, Annexin V/Propidium iodide and JC-1 staining, transmission electron microscopy and confocal microscopy. Ceranib-2 effectively inhibited the viability of MCF7 cells in 24 h in a dose dependent manner leading to apoptosis via the mitochondrial pathway by reducing the potential of mitochondrial membrane. Additionally, significant changes on cell morphology and ultrastructure were observed on MCF7 cells exposed to ceranib-2 indicating apoptotic cell death. Collectively, our data demonstrate that ceranib-2 exerts a great potential to be an antineoplastic compound and that the mechanism of its action rely on its apoptosis inducing ability. PMID- 27380966 TI - Real-time monitoring of hypertrophy in HL-1 cardiomyocytes by impedance measurements reveals different modes of growth. AB - Hypertrophic growth is a response of the heart to increased mechanical load or physiological stress. Thereby, cardiomyocytes grow in length and/or width to maintain cardiac pump function. Major signaling pathways involved in cardiomyocyte growth and remodeling have been identified during recent years including calcineurin-NFAT and PI3K-Akt signaling. Modulation of these pathways is of certain interest for therapeutic treatment of cardiac hypertrophy. However, quantification and characterization of hypertrophy in response to different stimuli or modulators is difficult. This study aims to test different read-out systems for detection and quantification of differences in hypertrophic growth in response to prohypertrophic stimuli. Real-time impedance measurements allowed the detection of distinct differences in hypertrophic growth in response to endothelin, norepinephrine, phenylephrine or BIO, which were not observable by other methods such as flow cytometry. Endothelin treatment induced a rapid and strong peak in the impedance signal concomitant with a massive reorientation of the actin cytoskeleton. Changes in expression of hypertrophy-associated genes were detected and stabilization of beta-catenin was identified as a common response to all hypertrophic stimuli used in this study. Hypertrophic growth was blocked by the PI3K/mTOR inhibitor PI-103. PMID- 27380968 TI - A hemocyte-expressed fibrinogen-related protein gene (LvFrep) from the shrimp Litopenaeus vannamei: Expression analysis after microbial infection and during larval development. AB - Fibrinogen-related proteins (FREPs) comprise a large family of microbial recognition proteins involved in many biological functions in both vertebrate and invertebrate animals. By taking advantage of publicly accessible databases, we have identified a FREP-like homolog in the most cultivated penaeid shrimp, Litopenaeus vannamei (LvFrep). The obtained sequence showed a conserved fibrinogen-related domain (FReD) and displayed significant similarities to FREP like proteins from other invertebrates and to ficolins from crustaceans. The expression of LvFrep appeared to be limited to circulating hemocytes. Interestingly, LvFrep gene expression was induced in shrimp hemocytes only in response to a Vibrio infection but not to the White spot syndrome virus (WSSV). Moreover, LvFrep transcript levels were detected early in fertilized eggs, suggesting the participation of this immune-related gene in the antimicrobial defenses during shrimp development. PMID- 27380967 TI - Aging, Clonality, and Rejuvenation of Hematopoietic Stem Cells. AB - Aging is associated with reduced organ function and increased disease incidence. Hematopoietic stem cell (HSC) aging driven by both cell intrinsic and extrinsic factors is linked to impaired HSC self-renewal and regeneration, aging-associated immune remodeling, and increased leukemia incidence. Compromised DNA damage responses and the increased production of reactive oxygen species (ROS) have been previously causatively attributed to HSC aging. However, recent paradigm-shifting concepts, such as global epigenetic and cytoskeletal polarity shifts, cellular senescence, as well as the clonal selection of HSCs upon aging, provide new insights into HSC aging mechanisms. Rejuvenating agents that can reprogram the epigenetic status of aged HSCs or senolytic drugs that selectively deplete senescent cells provide promising translational avenues for attenuating hematopoietic aging and, potentially, alleviating aging-associated immune remodeling and myeloid malignancies. PMID- 27380970 TI - The relevance of indexed journals. PMID- 27380969 TI - Learning-based subject-specific estimation of dynamic maps of cortical morphology at missing time points in longitudinal infant studies. AB - Longitudinal neuroimaging analysis of the dynamic brain development in infants has received increasing attention recently. Many studies expect a complete longitudinal dataset in order to accurately chart the brain developmental trajectories. However, in practice, a large portion of subjects in longitudinal studies often have missing data at certain time points, due to various reasons such as the absence of scan or poor image quality. To make better use of these incomplete longitudinal data, in this paper, we propose a novel machine learning based method to estimate the subject-specific, vertex-wise cortical morphological attributes at the missing time points in longitudinal infant studies. Specifically, we develop a customized regression forest, named dynamically assembled regression forest (DARF), as the core regression tool. DARF ensures the spatial smoothness of the estimated maps for vertex-wise cortical morphological attributes and also greatly reduces the computational cost. By employing a pairwise estimation followed by a joint refinement, our method is able to fully exploit the available information from both subjects with complete scans and subjects with missing scans for estimation of the missing cortical attribute maps. The proposed method has been applied to estimating the dynamic cortical thickness maps at missing time points in an incomplete longitudinal infant dataset, which includes 31 healthy infant subjects, each having up to five time points in the first postnatal year. The experimental results indicate that our proposed framework can accurately estimate the subject-specific vertex-wise cortical thickness maps at missing time points, with the average error less than 0.23 mm. Hum Brain Mapp 37:4129-4147, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27380971 TI - Genetic perspective of retinoblastoma: From present to future. AB - Retinoblastoma (RB) is the most common malignant intraocular tumor in children. In the last decade, basic research has led to a better understanding of events after two hits in RB susceptibility gene (RB1), molecular mechanism of tumor growth, the cell of origin of RB, etc. This would pave way to identify biomarkers and molecular targeted therapy for better treatment option in the future. Furthermore, improvement in molecular techniques has led to enhanced diagnostic methods for early diagnosis, genetic counseling, and prevention of the disease. This review will help to understand the essence of basic research work conducted in recent times and its implication in the management of RB in the future. PMID- 27380972 TI - Fungal infections of the orbit. AB - Fungal infections of the orbit can lead to grave complications. Although the primary site of inoculation of the infective organism is frequently the sinuses, the patients can initially present to the ophthalmologist with ocular signs and symptoms. Due to its varied and nonspecific clinical features, especially in the early stages, patients are frequently misdiagnosed and even treated with steroids which worsen the situation leading to dire consequences. Ophthalmologists should be familiar with the clinical spectrum of disease and the variable presentation of this infection, as early diagnosis and rapid institution of appropriate therapy are crucial elements in the management of this invasive sino-orbital infection. In this review, relevant clinical, microbiological, and imaging findings are discussed along with the current consensus on local and systemic management. We review the recent literature and provide a comprehensive analysis. In the immunocompromised, as well as in healthy patients, a high index of suspicion must be maintained as delay in diagnosis of fungal pathology may lead to disfiguring morbidity or even mortality. Obtaining adequate diagnostic material for pathological and microbiological examination is critical. Newer methods of therapy, particularly oral voriconazole and topical amphotericin B, may be beneficial in selected patients. PMID- 27380974 TI - Lamina depth and thickness correlate with glaucoma severity. AB - PURPOSE: To evaluate the correlation between lamina cribrosa (LC) morphology and glaucoma severity in patients with primary forms of open-angle glaucoma (OAG) using enhanced depth imaging spectral-domain optical coherence tomography (SD OCT) and Humphrey visual field test (HVF). SUBJECTS AND METHODS: Patients with OAG (n = 166), divided into normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) groups (n = 66 and n = 100), were imaged using SD-OCT to obtain horizontal B-scan images of the optic nerve head (ONH). Laminar depth (LD) and laminar thickness (LT) were measured at the center of ONH. RESULTS: The mean (+/ standard deviation) values of LD, LT, and visual field mean deviation (MD) were 555.4 +/- 142.3 MUm, 179.9 +/- 49.7 MUm, and - 5.7 +/- 6.4 dB, respectively. In the multivariate linear regression analysis, LD, LT, and intraocular pressure (IOP) were significantly correlated with MD (P = 0.007, P = 0.037, and P = 0.004, respectively). In the subgroup analyses, only LD was associated with MD in the NTG group (n = 66), whereas LT and IOP were correlated with MD in the HTG group (n = 100). Neither axial length nor central corneal thickness was associated with LD or LT. CONCLUSIONS: Glaucoma severity, as measured by HVF MD, shows significant correlations with LD and LT, with greater severity associated with increasing LD and decreasing LT. Normal- and high-tension OAG patients have different associations with LD and LT, which implies that the pathogenesis of these two entities might be different. PMID- 27380973 TI - Recent advances in diagnosis and management of Mycotic Keratitis. AB - Mycotic keratitis is a major cause of corneal blindness, especially in tropical and subtropical countries. The prognosis is markedly worse compared to bacterial keratitis. Delayed diagnosis and scarcity of effective antifungal agents are the major factors for poor outcome. Over the last decade, considerable progress has been made to rapidly diagnose cases with mycotic keratitis and increase the efficacy of treatment. This review article discusses the recent advances in diagnosis and management of mycotic keratitis with a brief discussion on rare and emerging organisms. A MEDLINE search was carried out for articles in English language, with the keywords, mycotic keratitis, fungal keratitis, emerging or atypical fungal pathogens in mycotic keratitis, investigations in mycotic keratitis, polymerase chain reaction in mycotic keratitis, confocal microscopy, treatment of mycotic keratitis, newer therapy for mycotic keratitis. All relevant articles were included in this review. Considering the limited studies available on newer diagnostic and therapeutic modalities in mycotic keratitis, case series as well as case reports were also included if felt important. PMID- 27380975 TI - A novel splice donor site mutation in EPHA2 caused congenital cataract in a Chinese family. AB - BACKGROUND: Congenital cataract is a rare disorder characterized by crystallin denaturation, which becomes a major cause of childhood blindness. Although more than fifty pathogenic genes for congenital cataract have been reported, the genetic causes of many cataract patients remain unknown. In this study, the aim is to identify the genetic cause of a five-generation Chinese autosomal dominant congenital cataract family. METHODS: Whole exome sequencing (WES) was performed on three affected and one unaffected member of the family, known causative genes were scanned first. Sanger sequencing was used to validate co-segregation of the candidate variant in the family. The impact on the transcript and amino acid sequences of the variant was further analyzed. RESULTS: We identified a novel splice donor site mutation c. 2825+1G >A in EPHA2 that was absent in public and in-house databases and showed co-segregation in the family. This variant resulted in an altered splice that led to protein truncation. CONCLUSIONS: The mutation we identified was responsible for congenital cataract in our studied family. Our findings broaden the spectrum of causative mutations in EPHA2 gene for congenital cataract and suggest that WES is an efficient strategy to scan variants in known causative genes for genetically heterogeneous diseases. PMID- 27380976 TI - Vitreoretinal lymphomas misdiagnosed as uveitis: Lessons learned from a case series. AB - PURPOSE: To present challenging cases of vitreoretinal lymphoma (VRL) that was misdiagnosed as uveitis because of the apparent intraocular inflammation. At the light of the new classification of intraocular lymphomas, we detail the characteristics that masqueraded the tumors and the clinical aspects that guided us to the correct diagnosis. MATERIALS AND METHODS: We retrospectively reviewed the patients referred to our uveitis service between January 2006 and December 2014. RESULTS: Seven patients referred with a presumptive diagnosis of idiopathic uveitis received a final diagnosis of VRL. The median time between the onset of symptoms and definitive diagnosis was 25 months for these complex cases. The median time from presentation at our clinic to final diagnosis was 1 month. The described clinical features including dense vitreous cells and subretinal infiltrates were characteristic and tend to be present in all these chronically ill patients. Vitreous samples were collected, and all demonstrated the pathognomonic tumor cells, the specific immunoglobulin heavy chain gene rearrangements, and an interleukin (IL)-10 to IL-6 ratio >1. CONCLUSION: VRLs are severe diseases with a poor prognosis that may be misdiagnosed as idiopathic inflammatory conditions of the eye. Treatment with steroids may occult the tumors and delay the correct diagnosis. Appropriate evaluation may prompt to a timely vitreous sampling and therefore to a faster diagnosis in these peculiar cases where the correct diagnosis was delayed by several months. PMID- 27380977 TI - The efficacy of intravitreal interferon alpha-2b for the treatment of experimental endotoxin-induced uveitis. AB - PURPOSE: To study the efficacy of intravitreal interferon alpha-2b for endotoxin induced uveitis. MATERIALS AND METHODS: A total of 36 rabbits were randomly allocated to one of the three groups: (1) received interferon plus balanced-salt solution; (2) received lipopolysaccharide (LPS) plus interferon; and (3) received LPS plus balanced-salt solution. Intraocular inflammation was evaluated by slit lamp biomicroscopy (standardization of uveitis nomenclature grading), binocular indirect ophthalmoscopy (BIO) score, and histopathology. RESULTS: Group 2 showed significantly lower mean (+/-standard deviation) anterior chamber reaction than Group 3 (3.1 +/- 0.9 vs. 3.8 +/- 0.4) on day 1 postinjection, lower vitreous cells on days 1 through 7 (day 1: 3.1 +/- 0.9 vs. 3.8 +/- 0.4; day 3: 2.1 +/- 1.6 vs. 3.8 +/- 0.4; day 7: 1.9 +/- 1.3 vs. 3.6 +/- 0.7), and lower BIO score on days 1-7 (day 1: 3.3 +/- 1.2 vs. 4.4 +/- 0.7; day 3: 3.0 +/- 1.4 vs. 4.3 +/- 0.9; day 7: 2.4 +/- 1.4 vs. 3.7 +/- 1.2). The protein content of anterior and vitreous aspirates was lower in Group 2 than 3 (1618.5 +/- 411.4 vs. 2567.3 +/- 330.8 and 2157.0 +/- 283.3 vs. 3204.6 +/- 259.5, respectively). CONCLUSION: Intravitreal interferon alpha-2b was effective in controlling endotoxin-induced uveitis. PMID- 27380978 TI - Wavefront aberration and contrast sensitivity after implantation of foldable and rigid iris claw phakic intraocular lenses: Artiflex versus artisan. AB - AIM OF STUDY: The aim of this study is to assess wavefront aberration and contrast sensitivity (CS) after implantation of foldable iris claw - artiflex- and rigid iris claw - artisan- phakic intraocular lenses (pIOLs). MATERIALS AND METHODS: A nonrandomized prospective comparative case study was performed on 57 eyes; of which, 54 were myopia and 3 were hyperopia. Twenty-four patients had artisan pIOL implantation and 33 had artiflex pIOL implantation. Higher-order aberration (HOA) and CS were obtained 1 year after surgery. RESULTS: Total HOA in artisan group was greater than artiflex group (P = 0.044) with a mean HOA of 0.44 +/- 0.15 root mean square (RMS) for artisan and 0.35 +/- 0.15 RMS for artiflex. Although, there were no significant differences in the vertical trefoil, vertical coma, horizontal trefoil, horizontal coma, secondary astigmatism, quatrefoil, and fourth order spherical aberration in two groups. CS in mesopic conditions was better in artiflex-treated eyes at three spatial frequencies of 6, 12, and 18 cycles per degree (cpd) (P = 0.003, P = 0.007, and P = 0.00, respectively), and no significant difference was seen between two lenses at 3 cpd. CONCLUSION: Although the components of HOA were not significantly different between two groups, total HOA was higher in artisan group, which may be due to the slight differences in each component, increasing the HOA as a total. CS was significantly better in artiflex group. PMID- 27380979 TI - Prevalence of visual impairment due to uncorrected refractive error: Results from Delhi-Rapid Assessment of Visual Impairment Study. AB - AIM: To estimate the prevalence of visual impairment (VI) due to uncorrected refractive error (URE) and to assess the barriers to utilization of services in the adult urban population of Delhi. MATERIALS AND METHODS: A population-based rapid assessment of VI was conducted among people aged 40 years and above in 24 randomly selected clusters of East Delhi district. Presenting visual acuity (PVA) was assessed in each eye using Snellen's "E" chart. Pinhole examination was done if PVA was <20/60 in either eye and ocular examination to ascertain the cause of VI. Barriers to utilization of services for refractive error were recorded with questionnaires. RESULTS: Of 2421 individuals enumerated, 2331 (96%) individuals were examined. Females were 50.7% among them. The mean age of all examined subjects was 51.32 +/- 10.5 years (standard deviation). VI in either eye due to URE was present in 275 individuals (11.8%, 95% confidence interval [CI]: 10.5 13.1). URE was identified as the most common cause (53.4%) of VI. The overall prevalence of VI due to URE in the study population was 6.1% (95% CI: 5.1-7.0). The elder population as well as females were more likely to have VI due to URE (odds ratio [OR] = 12.3; P < 0.001 and OR = 1.5; P < 0.02). Lack of felt need was the most common reported barrier (31.5%). CONCLUSIONS: The prevalence of VI due to URE among the urban adult population of Delhi is still high despite the availability of abundant eye care facilities. The majority of reported barriers are related to human behavior and attitude toward the refractive error. Understanding these aspects will help in planning appropriate strategies to eliminate VI due to URE. PMID- 27380980 TI - Imaging for branching vascular network in polypoidal choroidal vasculopathy. PMID- 27380981 TI - Interferon alpha-2b in giant ocular surface squamous neoplasia. PMID- 27380982 TI - Multimodal imaging in multifocal pattern dystrophy simulating fundus flavimaculatus. PMID- 27380983 TI - Congenital third nerve palsy with synergistic depression on attempted adduction and trigemino-oculomotor synkinesis: Underpinnings of a spectral dysinnervation disorder. AB - The authors describe a case of congenital partial pupil-sparing third cranial nerve palsy with absent adduction, synergistic depression of globe and widening of palpebral fissure on attempted adduction and synergistic elevation and adduction on mouth opening and sideways thrusting of jaw. The case illustrates trigemino-oculomotor synkinesis associated with congenital third nerve palsy. The possible mechanism of miswiring involving the medial longitudinal fasciculus and trigeminal nuclei is discussed. At least some cases of congenital third cranial nerve palsy may fall in the realm of congenital cranial dysinnervation disorders (CCDDs) sharing a much wider spectrum of presentation. PMID- 27380985 TI - Spindle cell carcinoma of the conjunctiva: A rare entity. AB - An 85-year-old male presented with painless bulging lesion over the cornea. Clinical history, diagnostic imaging studies, and histopathologic sections were evaluated. The patient clinically displayed an vascularized conjunctival lesion located at the superior bulbar conjunctiva with extension onto cornea covering 2/3 of his pupillary aperture superiorly. His visual acuity was counting fingers at 4 m. The patient underwent a total excision of the lesion including conjunctival and corneal parts. Histopathologic evaluation revealed spindle cell carcinoma which involves the whole conjunctival squamous epithelium with significant polarity loss, nuclear enlargement with hyperchromasia and pleomorphism, and mitotic activity. Diagnosis of spindle cell carcinoma is challenging because of overlapping histopathological features with other spindle cell tumors. The detailed pathologic examination is very important for the decision of proper treatment. PMID- 27380984 TI - How genetics works? An illustrative case report. AB - In this communication, we report the case of a four year old boy who presented with reduced vision in the right eye. He had visual acuity of light perception right eye and 6/12 in the left eye and anterior segment examination was normal. Fundus examination of the right eye showed a falciform retinal fold extending from the optic nerve temporally involving the entire retina with exudates within the falciform fold and dense pigmentation peripherally. The left eye showed mild macular temporal dragging of the vessels and 360 degrees of peripheral laser scars. In addition he also had some characteristic systemic features such as developmental delay, obesity, dysmorphic facies and tapered fingers. Using this case as an example, we present a systematic, logical approach to a patient with a possible genetic disorder. The growing field of ocular genetics now allows for improved diagnosis using step-wise cost efficient testing as demonstrated herein. PMID- 27380986 TI - Comment on: Learning curves for strabismus surgery in two ophthalmologists. PMID- 27380987 TI - Comment on: Impact of vitreoretinal surgery experience on strabismus surgery performance. PMID- 27380988 TI - Comment on: Bilateral lateral rectus myotoxicity after retrobulbar anesthesia. PMID- 27380989 TI - Comment on: Choroidal thickness changes after dynamic exercise as measured by spectral-domain optical coherence tomography. PMID- 27380990 TI - Comment on: The effect of anterior transposition of the inferior oblique muscle on eyelid configuration and function. PMID- 27380991 TI - Erratum: A case of perforating injury of eyeball and traumatic cataract caused by acupuncture. AB - [This corrects the article DOI: 10.4103/0301-4738.182952]. PMID- 27380992 TI - Comparison of large networks with sub-sampling strategies. AB - Networks are routinely used to represent large data sets, making the comparison of networks a tantalizing research question in many areas. Techniques for such analysis vary from simply comparing network summary statistics to sophisticated but computationally expensive alignment-based approaches. Most existing methods either do not generalize well to different types of networks or do not provide a quantitative similarity score between networks. In contrast, alignment-free topology based network similarity scores empower us to analyse large sets of networks containing different types and sizes of data. Netdis is such a score that defines network similarity through the counts of small sub-graphs in the local neighbourhood of all nodes. Here, we introduce a sub-sampling procedure based on neighbourhoods which links naturally with the framework of network comparisons through local neighbourhood comparisons. Our theoretical arguments justify basing the Netdis statistic on a sample of similar-sized neighbourhoods. Our tests on empirical and synthetic datasets indicate that often only 10% of the neighbourhoods of a network suffice for optimal performance, leading to a drastic reduction in computational requirements. The sampling procedure is applicable even when only a small sample of the network is known, and thus provides a novel tool for network comparison of very large and potentially incomplete datasets. PMID- 27380994 TI - In vitro inhibition of Toxoplasma gondii by the anti-malarial candidate, 6 (1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol. AB - An anti-malarial candidate, 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251), was studied to characterize its potential as a novel anti-Toxoplasma gondii drug. In the present study, IC50 and LC50 of N-251 on host cells and T. gondii were compared to those of artemisinin and sulfadiazine. The IC50 on Huh-7 cells was 10.19MUg/ml, 67.69MUg/ml and 310.17MUg/ml for N-251, artemisinin, and sulfadiazine, respectively. The LC50 for anti-T. gondii effect was shown to be 1.11MUg/ml, 5.79MUg/ml, and 5.45MUg/ml for N-251, artemisinin and sulfadiazine, respectively. N-251 concentration causing complete parasiticidal effect with minimal cytotoxicity on host cells was determined to be 5MUg/ml. Additionally, the anti-T. gondii effect of N-251 was confirmed by ultrastructural changes, loss of organelles, degenerated morphology and the increase of amylopectin as detected by transmission electron microscope (TEM). Accordingly, the present study suggests that the anti-malarial synthetic endoperoxide, N-251, is an emerging drug candidate more effective than artemisinin and sulfadiazine. PMID- 27380993 TI - Predictive ability of the Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification system following infrapopliteal endovascular interventions for critical limb ischemia. AB - OBJECTIVE: The Society for Vascular Surgery (SVS) Lower Extremity Guidelines Committee has composed a new threatened lower extremity classification system that reflects the three major factors that impact amputation risk and clinical management: Wound, Ischemia, and foot Infection (WIfI). Our goal was to evaluate the predictive ability of this scale following any infrapopliteal endovascular intervention for critical limb ischemia (CLI). METHODS: From 2004 to 2014, a single institution, retrospective chart review was performed at the Beth Israel Deaconess Medical Center for all patients undergoing an infrapopliteal angioplasty for CLI. Throughout these years, 673 limbs underwent an infrapopliteal endovascular intervention for tissue loss (77%), rest pain (13%), stenosis of a previously treated vessel (5%), acute limb ischemia (3%), or claudication (2%). Limbs missing a grade in any WIfI component were excluded. Limbs were stratified into clinical stages 1 to 4 based on the SVS WIfI classification for 1-year amputation risk, as well as a novel WIfI composite score from 0 to 9. Outcomes included patient functional capacity, living status, wound healing, major amputation, major adverse limb events, reintervention, major amputation, or stenosis (RAS) events (> *3.5 step-up by duplex), amputation-free survival, and mortality. Predictors were identified using Kaplan-Meier survival estimates and Cox regression models. RESULTS: Of the 596 limbs with CLI, 551 were classified in all three WIfI domains on a scale of 0 (least severe) to 3 (most severe). Of these 551, 84% were treated for tissue loss and 16% for rest pain. A Cox regression model illustrated that an increase in clinical stage increases the rate of major amputation (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.1-2.3). Separate regression models showed that a one-unit increase in the WIfI composite score is associated with a decrease in wound healing (HR, 1.2; 95% CI, 1.1-1.4) and an increase in the rate of RAS events (HR, 1.2; 95% CI, 1.1-1.4) and major amputations (HR, 1.4; 95% CI, 1.2-1.8). CONCLUSIONS: This study supports the ability of the SVS WIfI classification system to predict 1-year amputation, RAS events, and wound healing in patients with CLI undergoing endovascular infrapopliteal revascularization procedures. PMID- 27380995 TI - Long-term endurance and safety of elosulfase alfa enzyme replacement therapy in patients with Morquio A syndrome. AB - Long-term efficacy and safety of elosulfase alfa enzyme replacement therapy were evaluated in Morquio A patients over 96weeks (reaching 120weeks in total from pre treatment baseline) in an open-label, multi-center, phase III extension study. During this extension of a 24-week placebo-controlled phase III study, all patients initially received 2.0mg/kg elosulfase alfa either weekly or every other week, prior to establishment of 2.0mg/kg/week as the recommended dose, at which point all patients received weekly treatment. Efficacy measures were compared to baseline of the initial 24-week study, enabling analyses of changes over 120weeks. In addition to performing analyses for the entire intent-to-treat (ITT) population (N=173), analyses were also performed for a modified per-protocol (MPP) population (N=124), which excluded patients who had orthopedic surgery during the extension study or were non-compliant with the study protocol (as determined by >=20% missed infusions). Six-minute walk test (6MWT) was the primary efficacy measure; three-minute stair climb test (3MSCT) and normalized urine keratan sulfate (uKS) were secondary efficacy measures. Mean (SE) change from baseline to Week 120 in 6MWT distance was 32.0 (11.3)m and 39.9 (10.1)m for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study (N=56) and 15.1 (7.1)m and 31.7 (6.8)m in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively. Further analyses revealed that durability of 6MWT improvements was not impacted by baseline 6MWT distance, use of a walking aid, or age. Mean (SE) change at Week 120 in the 3MSCT was 5.5 (1.9) and 6.7 (2.0)stairs/min for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study and 4.3 (1.2) and 6.8 (1.3)stairs/min in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively Across all patients, mean (SE) change at Week 120 in normalized uKS was -59.4 (1.8)% and -62.3 (1.8)% in the ITT and MPP populations, respectively. In the absence of a placebo group, significance of the sustained improvements could not be evaluated directly. However, to provide context for interpretation of results, comparisons were performed with untreated patients from a Morquio A natural history study. In contrast to the results of the extension study, the untreated patients experienced constant uKS levels and a gradual decline in endurance test results over a similar period of time. Differences from the untreated natural history study patients were significant for 6MWT, 3MSCT, and uKS outcomes for the cohort of patients receiving optimal dosing throughout the study and for all cohorts pooled together, for both ITT and MPP populations (P<0.05). Safety findings were consistent with those of the initial 24-week study, with no new safety signals identified. PMID- 27380996 TI - CBP/p300 acetyltransferase activity in hematologic malignancies. AB - CREB binding protein (CBP) and p300 are critical regulators of hematopoiesis through both their transcriptional coactivator and acetyltransferase activities. Loss or mutation of CBP/p300 results in hematologic deficiencies in proliferation and differentiation as well as disruption of hematopoietic stem cell renewal and the microenvironment. Aberrant lysine acetylation mediated by CBP/p300 has recently been implicated in the genesis of multiple hematologic cancers. Understanding the effects of disrupting the acetyltransferase activity of CBP/p300 could pave the way for new therapeutic approaches to treat patients with these diseases. PMID- 27380997 TI - The impact of protein extraction protocols on the performance of currently available MALDI-TOF mass spectrometry for identification of mycobacterial clinical isolates cultured in liquid media. AB - BACKGROUND: Protein extraction step is particularly important for identification of mycobacterial isolates by MALDI-TOF mass spectrometry (MS) because of its thick and solid cell wall. This study compared the performance of MALDI-TOF MS for identification of mycobacterial clinical isolates cultured in liquid media between heating-based protocol and non-heating protocol. METHODS: Clinical mycobacterial isolates cultured in liquid media were prospectively analyzed. Reference identification was real-time PCR and restriction fragment length polymorphism. The specimens prepared by heating protocol and non-heating protocol were tested using MALDI Biotyper (Bruker Daltonics, Bremen, Germany) and Vitek MS (bioMerieux, Marcy l'Etoile, France), respectively. RESULTS: Among the 206 clinical specimens prepared by heating method, identification rates were 90.3% and 60.7% in MALDI Biotyper and Vitek MS, respectively. Identification accuracy of MALDI Biotyper and Vitek MS was 100% for the isolates of Mycobacterium tuberculosis complex (MTBC), Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium abscessus and Mycobacterium fortuitum. Among the 121 clinical specimens prepared by non-heating method, identification rate for MALDI Biotyper and Vitek MS were 61.2% and 69.4%, respectively. Identification accuracy of MALDI Biotyper/Vitek MS were 92.9%/94.1% for MTBC, 92.9%/100% for M. avium, 90%/100% for M. intracellulare, 100%/100% for M. abscessus and 100%/100% for M. fortuitum. CONCLUSIONS: The performance of MALDI-TOF MS for identification of mycobacterial clinical isolates is affected by protein extraction protocol. For best performance, protein extraction protocol should be chosen considering the MALDI TOF MS system. In the present study, heating protocol with MALDI Biotyper system showed reliable identification results for mycobacterial clinical isolates. PMID- 27380998 TI - Biomarkers of cardiovascular stress in obstructive sleep apnea. AB - Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder associated with "cardiovascular stress", i.e. cardiovascular risk factors, cardiovascular diseases, and an increased risk of heart failure, stroke, and death. Experimental and clinical studies have characterized potential underlying mechanisms including biventricular dysfunction, atherosclerosis, and arrhythmia. Assessment of these cardiovascular features of OSA requires a spectrum of clinical tools including ECG, echocardiography, exercise testing, and angiography. In contrast to many cardiovascular diseases, the role of blood biomarkers to characterize cardiovascular function and cardiovascular risk in OSA is poorly defined. In the present review we summarize the available data on biomarkers potentially providing information on cardiovascular features in OSA patients without overt cardiovascular disease. The vast majority of studies on biomarkers of cardiovascular stress in OSA evaluated B-type natriuretic peptide (BNP)/N-terminal-B-type natriuretic peptide (NT-proBNP), and cardiac troponins (cTn). Although some studies found significant associations between these cardiac biomarkers and the presence and severity of OSA, data remain conflicting. Also, the detailed pathophysiological mechanisms underlying the link between OSA and hemodynamic cardiac stress (BNP/NT-proBNP) and cardiomyocyte damage (cTn) are poorly understood. Major research efforts are required to establish the clinical role of cardiovascular biomarkers in patients with OSA. PMID- 27380999 TI - Caspase-3 in serum predicts outcome after aneurysmal subarachnoid hemorrhage. AB - BACKGROUND: Caspase-3 represents a promising marker of apoptosis. This study was designed to investigate the serial change of serum caspase-3 activities and analyze the relationships between caspase-3 activities and the severity and prognosis of aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We determined serum caspase-3 activities of 118 controls at study entry and 118 patients at admission and at days 1, 2, 3, 5 and 7 after aSAH. Activities were compared with regard to (i) time interval between onset of symptoms and blood sampling, (ii) stroke severity quantified by World Federation of Neurological Surgeons (WFNS) scores and modified Fisher scores and (iii) 6-month outcome. RESULTS: Serum caspase-3 activities were increased after aSAH, peaked at day 3, gradually decreased afterwards, and substantially were higher in patients than in controls. Caspase-3 activities were higher in patients suffering from death or an unfavorable outcome (Glasgow Outcome Scale score of 1-3), had close relation to WFNS scores and modified Fisher scores, and possessed high areas under receiver operating characteristic curve. Moreover, caspase-3 activities at admission and at day 3 predicted poor outcome independently of age, WFNS scores and modified Fisher scores. CONCLUSION: Increased serum caspase-3 activities are highly associated with the severity and prognosis after aSAH. PMID- 27381000 TI - Multifunctional gold nanocomposites designed for targeted CT/MR/optical trimodal imaging of human non-small cell lung cancer cells. AB - Multifunctional gold nanocomposites, which were designed as dendrimer-entrapped gold nanoparticles functionalized with gadolinium, cyanine dye (Cy5.5), and folic acid, were synthesized to be used as the first dendrimer-based clinical nanoprobes for targeted X-ray computed tomography/magnetic resonance/optical trimodal imaging in vitro and in vivo of human non-small cell cancer cells. PMID- 27381001 TI - Improving low-temperature performance of surface flow constructed wetlands using Potamogeton crispus L. plant. AB - In this study, enhanced organics and nitrogen removal efficiency in SFCWs by different submerged plants for polluted river water treatment under cold temperature was evaluated. High average removal efficiencies of COD (92.45%), NH4(+)-N (93.70%) and TN (55.62%) were achieved in experimental SFCWs with Potamogeton crispus compared with SFCWs with other plants. SFCWs with underground Phragmites australis root also presented better performance than the unplanted systems, indicating its positive role of contamination removal in winter. The results of this study indicated SFCWs with hardy submerged plant P. crispus could be a more effective and sustainable strategy for removing organics and nitrogen in shallow nutrient enriched river water ecosystems under cold climate. PMID- 27381002 TI - "What is the work of Recovery Oriented Practice? A systematic literature review". AB - Concepts of personal and social recovery in mental illness are constantly evolving because the journey is fluid and subject to change over time. Dynamic interactions between the complexities of human nature and mental illness create ever-altering landscapes of perplexity. The acknowledged ebb and flow of recovery in the presence of chronic and serious mental illness requires health professionals to provide a flexible suite of care, delivered through skills and methods that are responsive and meaningful to the recipient. We conducted a systematic search for qualitative literature that articulated the work of personally-supportive recovery-oriented practice (ROP) to determine the specific components of recovery-supportive work. Twenty-one articles were identified as meeting the inclusion criteria and were synthesized using a coding framework derived from Normalization Process Theory. We identified three kinds of recovery supportive work required from health professionals: alleviating stigma, delivering effective recovery-supportive responses in the presence of complex health and social situations and managing challenges associated with the work of ROP. We discuss the resources needed for ROP and the barriers that inhibit health professionals' engagement in this work. By elucidating the work of ROP, we highlighted a disparity between health professionals' aspirations and achievements. These revelations could inform service delivery in order to better support consumer recovery in serious mental illness. PMID- 27381004 TI - Knowledge and potential impact of the WHO Global code of practice on the international recruitment of health personnel: Does it matter for source and destination country stakeholders? AB - The WHO Global Code of Practice on the International Recruitment of Health Personnel was implemented in May 2010. The present commentary offers some insights into what is known about the Code five years on, as well as its potential impact, drawing from interviews with health care and policy stakeholders from a number of 'source' and 'destination' countries. PMID- 27381005 TI - 4-aminopyridine reverses ataxia and cerebellar firing deficiency in a mouse model of spinocerebellar ataxia type 6. AB - Spinocerebellar ataxia type 6 (SCA6) is a devastating midlife-onset autosomal dominant motor control disease with no known treatment. Using a hyper-expanded polyglutamine (84Q) knock-in mouse, we found that cerebellar Purkinje cell firing precision was degraded in heterozygous (SCA6(84Q/+)) mice at 19 months when motor deficits are observed. Similar alterations in firing precision and motor control were observed at disease onset at 7 months in homozygous (SCA6(84Q/84Q)) mice, as well as a reduction in firing rate. We further found that chronic administration of the FDA-approved drug 4-aminopyridine (4-AP), which targets potassium channels, alleviated motor coordination deficits and restored cerebellar Purkinje cell firing precision to wildtype (WT) levels in SCA6(84Q/84Q) mice both in acute slices and in vivo. These results provide a novel therapeutic approach for treating ataxic symptoms associated with SCA6. PMID- 27381006 TI - VIP impairs acquisition of the macrophage proinflammatory polarization profile. AB - This study tested the hypothesis that vasoactive intestinal peptide (VIP) is able to modify the macrophage inflammatory profile, thus supporting its therapeutic role in autoimmune diseases. Macrophages are innate immune cells that display a variety of functions and inflammatory profiles in response to the environment that critically controls their polarization. Deregulation between the pro- and anti-inflammatory phenotypes has been involved in different pathologies. Rheumatoid arthritis (RA) is an autoimmune disease, in which macrophages are considered central effectors of synovial inflammation, displaying a proinflammatory profile. VIP is a pleiotropic neuropeptide with proven anti inflammatory actions. As modulation of the macrophage phenotype has been implicated in the resolution of inflammatory diseases, we evaluated whether VIP is able to modulate human macrophage polarization. In vitro-polarized macrophages by GM-CSF (GM-MO), with a proinflammatory profile, expressed higher levels of VIP receptors, vasoactive intestinal polypeptide receptors 1 and 2 (VPAC1 and VPAC2, respectively), than macrophages polarized by M-CSF (M-MO) with anti-inflammatory activities. RA synovial macrophages, according to their GM-CSF-like polarization state, expressed both VPAC1 and VPAC2. In vitro-generated GM-MO exposed to VIP exhibited an up-regulation of M-MO gene marker expression, whereas their proinflammatory cytokine profile was reduced in favor of an anti-inflammatory function. Likewise, in GM-MO, generated in the presence of VIP, VIP somehow changes the macrophages physiology profile to a less-damaging phenotype. Therefore, these results add new value to VIP as an immunomodulatory agent on inflammatory diseases. PMID- 27381007 TI - PI3K p85 beta regulatory subunit deficiency does not affect NK cell differentiation and increases NKG2D-mediated activation. AB - Activation of NK cells depends on a balance between activating and inhibitory signals. Class Ia PI3K are heterodimeric proteins with a catalytic and a regulatory subunit and have a central role in cell signaling by associating with tyrosine kinase receptors to trigger signaling cascades. The regulatory p85 subunit participates in signaling through NKG2D, one of the main activating receptors on NK cells, via its interaction with the adaptor protein DAP10. Although the effects of inhibiting catalytic subunits or deleting the regulatory p85alpha subunit have been studied, little attention has focused on the role of the p85beta subunit in NK cells. Using p85beta knockout mice, we found that p85beta deficiency does not alter NK cell differentiation and maturation in spleen or bone marrow. NK cells from p85beta-/- mice nonetheless produced more IFN-gamma and degranulated more effectively when stimulated with anti-NKG2D antibody. These cells also degranulated and killed NKG2D ligand-expressing target cells more efficiently. We show that p85beta deficiency impaired NKG2D internalization, which could contribute to the activated phenotype. Decreasing p85beta subunit protein levels might thus constitute a therapeutic target to promote NK cell activity toward NKG2D ligand-expressing cells. PMID- 27381009 TI - Reactive oxygen species accelerate degradation of anion exchange membranes based on polyphenylene oxide in alkaline environments. AB - Anion exchange membranes (AEM) based on polyphenylene oxide (PPO) suffered quaternary-ammonium-cation-site degradation in alkaline environments. Surprisingly, the degradation rate was considerably faster in the presence of molecular oxygen. We postulated that the AEM cation-site catalyzes the reduction of dioxygen by hydroxide ions to yield the superoxide anion radical and the highly reactive hydroxyl free radical. We substantiated our hypothesis by using a phosphorous-containing spin trap (5-diisopropoxy-phosphoryl-5-methyl-1-pyrroline N-oxide) to detect the adducts for both free radicals in situ using (31)P-NMR spectroscopy. PMID- 27381008 TI - Self-assembly of c-myc DNA promoted by a single enantiomer ruthenium complex as a potential nuclear targeting gene carrier. AB - Gene therapy has long been limited in the clinic, due in part to the lack of safety and efficacy of the gene carrier. Herein, a single enantiomer ruthenium(II) complex, Lambda-[Ru(bpy)2(p-BEPIP)](ClO4)2 (Lambda-RM0627, bpy = 4,4'-bipyridine, p-BEPIP = 2-(4-phenylacetylenephenyl)imidazole [4,5f][1, 10] phenanthroline), has been synthesized and investigated as a potential gene carrier that targets the nucleus. In this report, it is shown that Lambda-RM0627 promotes self-assembly of c-myc DNA to form a nanowire structure. Further studies showed that the nano-assembly of c-myc DNA that induced Lambda-RM0627 could be efficiently taken up and enriched in the nuclei of HepG2 cells. After treatment of the nano-assembly of c-myc DNA with Lambda-RM0627, over-expression of c-myc in HepG2 cells was observed. In summary, Lambda-RM0627 played a key role in the transfer and release of c-myc into cells, which strongly indicates Lambda-RM0627 as a potent carrier of c-myc DNA that targets the nucleus of tumor cells. PMID- 27381010 TI - Participants' Accounts on Their Decision to Join a Cohort Study With an Attached Biobank: A Qualitative Content Analysis Study Within Two German Studies. AB - Reliable participation and sustained retention rates are crucial in longitudinal studies involving human subjects and biomaterials. Understanding the decision to enroll is an essential step to develop adequate strategies promoting long-term participation. Semi-structured interviews were implemented with newly recruited and long-term participants randomly drawn from two ongoing longitudinal studies with a biobank component in Germany. Iterative qualitative content analysis was applied to the transcribed interviews. Participants (n = 31) expressed their decision to enroll or remain in the study as the result of the complex interplay of individual factors, institutional cues, study-related features, and societal dynamics. Different forms of trust were identified as central within the elements used to explain participation and could be compared to Dibben, Morris, and Lean's dynamic model of interpersonal trust. Given these high levels of trust, an investigation of the morality of the trustful relationship at stake between participants and research(ers) is warranted. PMID- 27381011 TI - Large-Scale Synthesis of a Uniform Film of Bilayer MoS2 on Graphene for 2D Heterostructure Phototransistors. AB - The large-scale synthesis of atomically thin, layered MoS2/graphene heterostructures is of great interest in optoelectronic devices because of their unique properties. Herein, we present a scalable synthesis method to prepare centimeter-scale, continuous, and uniform films of bilayer MoS2 using low pressure chemical vapor deposition. This growth process was utilized to assemble a heterostructure by growing large-scale uniform films of bilayer MoS2 on graphene (G-MoS2/graphene). Atomic force microscopy, Raman spectra, and transmission electron microscopy characterization demonstrated that the large scale bilayer MoS2 film on graphene exhibited good thickness uniformity and a polycrystalline nature. A centimeter-scale phototransistor prepared using the G MoS2/graphene heterostructure exhibited a high responsivity of 32 mA/W with good cycling stability; this value is 1 order of magnitude higher than that of transferred MoS2 on graphene (2.5 mA/W). This feature results from efficient charge transfer at the interface enabled by intimate contact between the grown bilayer MoS2 (G-MoS2) and graphene. The ability to integrate multilayer materials into atomically thin heterostructures paves the way for fabricating multifunctional devices by controlling their layer structure. PMID- 27381012 TI - Bioimpedance spectroscopy in the infant: effect of milk intake and extracellular fluid reservoirs on resistance measurements in term breastfed infants. PMID- 27381013 TI - The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: a review of literature. PMID- 27381014 TI - Junior doctors reject proposed new contract. PMID- 27381015 TI - Solving local structure around dopants in metal nanoparticles with ab initio modeling of X-ray absorption near edge structure. AB - We adopted ab initio X-ray absorption near edge structure (XANES) modeling for structural refinement of local environments around metal impurities in a large variety of materials. Our method enables both direct modeling, where the candidate structures are known, and the inverse modeling, where the unknown structural motifs are deciphered from the experimental spectra. We present also estimates of systematic errors, and their influence on the stability and accuracy of the obtained results. We illustrate our approach by revealing the evolution of local environment of palladium atoms in palladium-doped gold thiolate clusters upon chemical and thermal treatments. PMID- 27381017 TI - Intestinal malrotation complicated by an occlusive syndrome involving internal hernia in a pregnant woman. AB - We present the case of a 33-year-old female who presented intestinal obstruction at the 7th month of pregnancy. She was complaining of abdominal pain with paroxysms, nausea and vomiting. When the symptoms worsened, we performed a CT scan, which revealed suspected intestinal obstruction in a context of intestinal malrotation (IM). Conservative therapy failed and she required emergency laparotomy beginning with a caesarean section. The surgery revealed a peritoneal defect due to the IM through which the jejunum and ileum were incarcerated and strangulated. The incarcerated bowel was reduced and intestinal colour quickly returned to normal. Primary closure of the peritoneal defect was thus performed and the post-operative course was uneventful for the mother and the baby, who was admitted to the neonatal intensive care unit. PMID- 27381018 TI - First case report of chylous ascites after robot-assisted donor nephrectomy. AB - We present the first case report of chylous ascites following total robot assisted donor nephrectomy. A 39-year-old female underwent a transperitoneal left sided total robot-assisted donor nephrectomy. The procedure was uneventful and the patient was discharged without any symptoms. At postoperative Day 29, the patient presented with abdominal pain, nausea and a distended, painful abdomen with shifting dullness. She was diagnosed with chylous ascites by ultrasonography and puncture analysis, and treated with therapeutic drainage and dietary restriction. After 4 weeks, she was free of symptoms. The occurrence of this complication is rare after donor nephrectomy. Fortunately, the complication can be successfully treated within a few weeks with minimal discomfort for the patient as demonstrated in this case. It is of utmost importance to minimize the risks and limit discomfort for live kidney donors who willingly undergo major surgery to improve the well-being of another individual. PMID- 27381019 TI - De Garengeot's hernia in an 82-year-old man: a case report and clinical significance. AB - The presence of the appendix within a femoral hernia (FH) sac is known as Garengeot's hernia (GH). We report on current study a rare case of an elderly man with a combined inguinal and Garengeot's hernia and discuss the clinical aspects. An 82-year-old man clinically stable, presented history of pain at the right inguinal region for over a week, without vomit, nausea, fever or any alteration of intestinal or urinary eliminations. Clinical examination revealed a FH and the ultrasonography confirmed the hernia sac. During the surgery, the appendix was recognized within the sac, and then, the patient underwent appendectomy and hernia repair. In conclusion, the presence of the vermiform appendix in a FH sac is rare, thus, requiring knowledge of the surgeon regarding this clinical entity. Prompt diagnosis and appropriate surgical treatment is the key to avoid complications. PMID- 27381020 TI - Local birthing services for rural women: Adaptation of a rural New South Wales maternity service. AB - OBJECTIVE: To describe the outcomes of a public hospital maternity unit in rural New South Wales (NSW) following the adaptation of the service from an obstetrician and general practitioner-obstetrician (GPO)-led birthing service to a low-risk midwifery group practice (MGP) model of care with a planned caesarean section service (PCS). DESIGN: A retrospective descriptive study using quantitative methodology. SETTING: Maternity unit in a small public hospital in rural New South Wales, Australia. PARTICIPANTS: Data were extracted from the ward based birth register for 1172 births at the service between July 2007 and June 2012. MAIN OUTCOME MEASURES: Birth numbers, maternal characteristics, labour, birthing and neonatal outcomes. RESULTS: There were 750 births over 29 months in GPO and 277 and 145 births over 31 months in MGP and PCS, respectively, totalling 422 births following the change in model of care. The GPO had 553 (73.7%) vaginal births and 197 (26.3%) caesarean section (CS) births (139 planned and 58 unplanned). There were almost universal normal vaginal births in MGP (>99% or 276). For normal vaginal births, more women in MGP had no analgesia (45.3% versus 25.1%) or non-invasive analgesia (47.9% versus 38.6%) and episiotomy was less common in MGP than GPO (1.9% versus 3.4%). Neonatal outcomes were similar for both groups with no difference between Apgar scores at 5 min, neonatal resuscitations or transfer to high-level special care nurseries. CONCLUSION: This study demonstrates how a rural maternity service maintained quality care outcomes for low-risk women following the adaptation from a GPO to an MGP service. PMID- 27381016 TI - The relationships of personal resources with symptom severity and psychosocial functioning in persons with schizophrenia: results from the Italian Network for Research on Psychoses study. AB - The relationships of personal resources with symptom severity and psychosocial functioning have never been tested systematically in a large sample of people with schizophrenia. We applied structural equation models to a sample of 921 patients with schizophrenia collected in a nationwide Italian study, with the aim to identify, among a large set of personal resources, those that may have an association with symptom severity or psychosocial functioning. Several relevant demographic and clinical variables were considered concurrently. Poor service engagement and poor recovery style, as well as older age and younger age at onset, were related to greater symptom severity and poorer social functioning. Higher resilience and higher education were related to better social functioning only. Poor problem-focused coping and internalized stigma, as well as male gender and depression, were related to symptom severity only. The explored variables showed distinctive and partially independent associations with symptom severity and psychosocial functioning. A deeper understanding of these relationships may inform treatment decisions. PMID- 27381021 TI - Salinicoccus amylolyticus sp. nov., isolated from a saltern. AB - A Gram-stain-positive coccus, strain JC304T, was isolated from a saltern of Nari along the Bhavnagar Coast, Gujarat, India. The 16S rRNA gene sequence analysis and sequence comparison data indicated that JC304T represented a member of the genus Salinicoccus and was most closely related to Salinicoccus roseus 9T (99.6 %), Salinicoccus luteus YIM 70202T (97.0 %), Salinicoccus hispanicus J-82T (97.0 %) and the remaining species of the genus Salinicoccus (<97 %). Genome relatedness based on DNA-DNA hybridization of JC304T with the type strains of the most closely related species was less than 46 % and the DeltaTmwas >5 degrees C indicating that the strain represents a novel species of the genus Salinicoccus. Independent and concatenated phylogenetic analysis of recA/fusA gene translated product showed a clear distinction of JC304T from its phylogenetic neighbors. Diphosphotidylglycerol, phosphatidylglycerol, an unidentified glycolipid and three unidentified lipids (L1, L2 and L3) were the polar lipids of JC304T. Iso C15 : 0 and anteiso-C15 : 0 were the major (>10 %) fatty acids in strain JC304T. The cell-wall amino acids were l-lysine and d-glycine. Hopanoids were not detected. The major isoprenoid quinone was menaquinone (MK-6). The DNA G+C content of JC304T was 48 mol%. On the basis of physiological, genotypic, phylogenetic and chemotaxonomic analyses, strain JC304T is considered to represent a novel species of the genus Salinicoccus, for which the name Salinicoccusamylolyticus sp. nov. is proposed. The type strain is JC304T (=KCTC 33661T=LMG 28757T). PMID- 27381022 TI - Challenges to implementation of the WHO Global Code of Practice on International Recruitment of Health Personnel: the case of Sudan. AB - BACKGROUND: The WHO Global Code of Practice on the International Recruitment of Health Personnel (hereafter the WHO Code) was adopted by the World Health Assembly in 2010 as a voluntary instrument to address challenges of health worker migration worldwide. To ascertain its relevance and effectiveness, the implementation of the WHO Code needs to be assessed based on country experience; hence, this case study on Sudan. METHODS: This qualitative study depended mainly on documentary sources in addition to key informant interviews. Experiences of the authors has informed the analysis. RESULTS: Migration of Sudanese health workers represents a major health system challenge. Over half of Sudanese physicians practice abroad and new trends are showing involvement of other professions and increased feminization. Traditional destinations include Gulf States, especially Saudi Arabia and Libya, as well as the United Kingdom and the Republic of Ireland. Low salaries, poor work environment, and a lack of adequate professional development are the leading push factors. Massive emigration of skilled health workers has jeopardized coverage and quality of healthcare and health professional education. Poor evidence, lack of a national policy, and active recruitment in addition to labour market problems were barriers for effective migration management in Sudan. Response of destination countries in relation to cooperative arrangements with Sudan as a source country has always been suboptimal, demonstrating less attention to solidarity and ethical dimensions. The WHO Code boosted Sudan's efforts to address health worker migration and health workforce development in general. Improving migration evidence, fostering a national dialogue, and promoting bilateral agreements in addition to catalysing health worker retention strategies are some of the benefits accrued. There are, however, limitations in publicity of the WHO Code and its incorporation into national laws and regulatory frameworks for ethical recruitment. The outlook is bleak for Sudan unless the country designs and implements a robust national policy for migration management and unless prospects for source-destination country collaboration improve within a more sound version of the WHO Code. CONCLUSIONS: The WHO Code catalysed some vital steps in managing migration and strengthening the national health workforce in Sudan. Nevertheless, the country has not utilized the full potential of this instrument. Revisions of the WHO Code would benefit much from lessons of its application in the context of developing countries such as Sudan. PMID- 27381024 TI - Strain mapping and correlative microscopy of the alveolar bone in a bone periodontal ligament-tooth fibrous joint. AB - This study details a method to calculate strains within interradicular alveolar bone using digital volume correlation on X-ray tomograms of intact bone periodontal ligament-tooth fibrous joints. The effects of loading schemes (concentric and eccentric) and optical magnification on the resulting strain in alveolar bone will be investigated with an intent to correlate deformation gradients with data sets from other complementary techniques. Strain maps will be correlated with structural and site-specific mechanical properties obtained on the same specimen using atomic force microscopy and atomic force microscopy-based nanoindentation technique. Specimens include polydimethylsiloxane as a standard material and intact hemi-mandibles harvested from rats. X-ray tomograms were taken at no-load and loaded conditions using an in situ load cell coupled to a micro X-ray computed tomography unit. Digital volume correlation was used to calculate deformations within alveolar bone. Comparison of strain maps was made as a result of different loading schemes (concentric vs eccentric) and at different magnifications (4* vs 10*). Virtual sections and strain maps from digital volume correlation solutions were aligned with structure and reduced elastic modulus to correlate datasets of the same region within a specimen. Strain distribution between concentrically and eccentrically loaded complexes was different but illustrated a similar range. Strain maps of homogeneous materials (polydimethylsiloxane) resulting from digital volume correlation at different magnifications were similar. However, strain maps of heterogeneous materials at lower and higher magnification differed. The digital volume correlation technique illustrated a dependence on optical magnification specifically for heterogeneous materials such as bone. The results at a higher optical magnification highlight the potential for extracting deformation at higher resolutions. Correlation of data spaces from different complementary techniques is plausible and could provide insights into biological and physicochemical processes that lead to functional adaptation of tissues and joints. PMID- 27381023 TI - Enhancers reside in a unique epigenetic environment during early zebrafish development. AB - BACKGROUND: Enhancers, not promoters, are the most dynamic in their DNA methylation status throughout development and differentiation. Generally speaking, enhancers that are primed to or actually drive gene expression are characterized by relatively low levels of DNA methylation (hypo-methylation), while inactive enhancers display hyper-methylation of the underlying DNA. The direct functional significance of the DNA methylation state of enhancers is, however, unclear for most loci. RESULTS: In contrast to conventional epigenetic interactions at enhancers, we find that DNA methylation status and enhancer activity during early zebrafish development display very unusual correlation characteristics: hypo-methylation is a unique feature of primed enhancers whereas active enhancers are generally hyper-methylated. The hypo-methylated enhancers that we identify (hypo-enhancers) are enriched close to important transcription factors that act later in development. Interestingly, hypo-enhancers are de methylated shortly before the midblastula transition and reside in a unique epigenetic environment. Finally, we demonstrate that hypo-enhancers do become active at later developmental stages and that they are physically associated with the transcriptional start site of target genes, irrespective of target gene activity. CONCLUSIONS: We demonstrate that early development in zebrafish embodies a time window characterized by non-canonical DNA methylation-enhancer relationships, including global DNA hypo-methylation of inactive enhancers and DNA hyper-methylation of active enhancers. PMID- 27381025 TI - Antifactor Xa levels vs. activated partial thromboplastin time for monitoring unfractionated heparin. A pilot study. AB - WHAT IS KNOWN AND OBJECTIVES: The two most common methods for monitoring unfractionated heparin (UFH) infusion are the activated partial thromboplastin time (aPTT) and the antifactor Xa heparin assay (anti-Xa). The purpose of this study is to compare the performance of an aPTT protocol vs. an anti-Xa protocol in adult patients as defined by the time to reach therapeutic range, the percentage of time the values were within the goal range and the number of times laboratory monitoring was conducted. We then analysed the discordance between paired values of anti-Xa and aPTT. METHODS: This was a single-centre prospective cohort pilot study conducted from 1 September 2013 to 31 May 2014. RESULTS: Eighty-five patients were treated with UFH infusion, aPTT monitoring (n = 48), anti-Xa monitoring (n = 37). The number of times aPTT and anti-Xa values were ordered was (median, IQR) 14 (2-34) vs 7 (2-76); P = 0.23. The time to reach therapeutic range in hours was (mean, SD) 22 (20) aPTT vs 15 (13) anti-Xa; P = 0.08. Therapeutic range (>50-100% of the time) was achieved in only 5 (10%) patients in the aPTT group vs. 21 (57%) in the anti-Xa group; P < 0.01. Supratherapeutic values (>50-100%) were observed in 38 (78%) patients in the aPTT group vs. 14 (38%) in the anti-Xa group; P < 0.01. The discordance between aPTT and anti-Xa was evaluated using 234 paired values from 37 patients. There was discordance between anti-Xa and aPTT values 57% of the time. Two patients had bleeding complications requiring blood transfusion or discontinuation of post pilot protocol. WHAT IS NEW AND CONCLUSION: Utilizing an anti-Xa protocol to monitor heparin infusion showed favourable results compared with utilizing an aPTT protocol by maintaining values within the therapeutic goal range. The most common discordant pattern in our study was a disproportionate prolongation of aPTT to anti-Xa values. Patients with discordant values presenting with high aPTT to normal anti-Xa values may have an increased risk of bleeding complications. PMID- 27381027 TI - Erratum to: Understanding the role of contrasting urban contexts in healthy aging: an international cohort study using wearable sensor devices (the CURHA study protocol). PMID- 27381026 TI - Electrostatic effects on the folding stability of FKBP12. AB - The roles of electrostatic interactions in protein folding stability have been a matter of debate, largely due to the complexity in the theoretical treatment of these interactions. We have developed computational methods for calculating electrostatic effects on protein folding stability. To rigorously test and further refine these methods, here we carried out experimental studies into electrostatic effects on the folding stability of the human 12-kD FK506 binding protein (FKBP12). This protein has a close homologue, FKBP12.6, with amino acid substitutions in only 18 of their 107 residues. Of the 18 substitutions, 8 involve charged residues. Upon mutating FKBP12 residues at these 8 positions individually into the counterparts in FKBP12.6, the unfolding free energy (DeltaGu) of FKBP12 changed by -0.3 to 0.7 kcal/mol. Accumulating stabilizing substitutions resulted in a mutant with a 0.9 kcal/mol increase in stability. Additional charge mutations were grafted from a thermophilic homologue, MtFKBP17, which aligns to FKBP12 with 31% sequence identity over 89 positions. Eleven such charge mutations were studied, with DeltaDeltaGu varying from -2.9 to 0.1 kcal/mol. The predicted electrostatic effects by our computational methods with refinements herein had a root-mean-square deviation of 0.9 kcal/mol from the experimental DeltaDeltaGu values on 16 single mutations of FKBP12. The difference in DeltaDeltaGu between mutations grafted from FKBP12.6 and those from MtFKBP17 suggests that more distant homologues are less able to provide guidance for enhancing folding stability. PMID- 27381028 TI - Standardized Documentation in Pediatric Diabetology: Experience From Austria and Germany. AB - This article gives a short summary of standardized documentation for pediatric diabetology from a European perspective. The approach chosen by the Austrian/German DPV (Diabetes Patienten Verlaufsdokumentation) group is detailed. The electronic health record used is briefly described, as are external benchmarking reports and national and international comparisons. Similar initiatives like the Hvidore study group, the SWEET initiative (Pediatric Diabetes: Working to Create Centers of Reference in Europe), and the T1DExchange (Type 1 Diabetes Exchange Registry) are compared to the DPV effort. PMID- 27381029 TI - If PBMs Guard Access to Drugs, Then Quis Custodiet Ipsos Custodies? (Who Will Guard the Guardians?). AB - Insulin prices in the United States have risen dramatically in recent years, yet pharmacies cannot provide a stable price for a given insulin due to factors that are not widely understood. This commentary discusses the complex and obscure factors that drive today's insulin prices with a discussion of the other players, besides the insulin manufacturer, who benefit from higher prices. An open discussion is critical regarding this drug and others that are essential to the lives of millions of people with diabetes. We'll also explore whether the market introduction of biosimilar insulin will impact insulin prices. PMID- 27381031 TI - Endocan to Predict Cardiovascular Events: A Promising Biomarker or a Coincidental Finding? PMID- 27381030 TI - How Much Is Short-Term Glucose Prediction in Type 1 Diabetes Improved by Adding Insulin Delivery and Meal Content Information to CGM Data? A Proof-of-Concept Study. AB - BACKGROUND: In type 1 diabetes (T1D) management, short-term glucose prediction can allow to anticipate therapeutic decisions when hypo/hyperglycemia is imminent. Literature prediction methods mainly use past continuous glucose monitoring (CGM) readings. Sophisticated algorithms can use information on insulin delivered and meal carbohydrate (CHO) content. The quantification of how much insulin and CHO information improves glucose prediction is missing in the literature and is investigated, in an open-loop setting, in this proof-of-concept study. METHODS: We adopted a versatile literature prediction methodology able to utilize a variety of inputs. We compared predictors that use (1) CGM; (2) CGM and insulin; (3) CGM and CHO; and (4) CGM, insulin, and CHO. Data of 15 T1D subjects in open-loop setup were used. Prediction was evaluated via absolute error and temporal gain focusing on meal/night periods. The relative importance of each individual input of the predictor was evaluated with a sensitivity analysis. RESULTS: For a prediction horizon (PH) >= 30 minutes, insulin and CHO information improves prediction accuracy of 10% and double the temporal gain during the 2 hours following the meal. During the night the 4 methods did not give statistically different results. When PH >= 45 minutes, the influence of CHO information on prediction is 5-fold that of insulin. CONCLUSIONS: In an open-loop setting, with PH >= 30 minutes, information on CHO and insulin improves short term glucose prediction in the 2-hour time window following a meal, but not during the night. CHO information improves prediction significantly more than insulin. PMID- 27381032 TI - Impact of Platelet-to-Lymphocyte Ratio on Clinical Outcomes in Patients With ST Segment Elevation Myocardial Infarction. AB - We investigated the association between platelet-to-lymphocyte ratio (PLR) and clinical outcomes (including all-cause mortality, recurrent myocardial infarction, heart failure, serious cardiac arrhythmias and ischemic stroke) in patients with ST-segment elevation myocardial infarction (STEMI). Based on PLR quartiles, 5886 patients with STEMI were categorized into 4 groups: <98.8 (n = 1470), 98.8 to 125.9 (n = 1474), 126.0 to 163.3 (n = 1478), >163.3 (n = 1464), respectively. We used Cox proportional hazards models to examine the relation between PLR and clinical outcomes. Mean duration of follow-up was 81.6 months, and 948 patients (16.1%) died during follow-up. The lowest mortality occurred in the lowest PLR quartile group ( P = 0.006), with an adjusted hazard ratio of 1.18 (95% confidence interval [CI], 1.04-1.55), 1.31 (95% CI, 1.18-1.64), and 1.59 (95% CI, 1.33-1.94) in patients with PLR of 98.8 to 125.9, 126.0 to 163.3, >163.3, respectively. Higher levels of PLR were also associated with recurrent myocardial infarction ( Ptrend = .023), heart failure ( Ptrend = .018), and ischemic stroke ( Ptrend = .043). In conclusion, a higher PLR was associated with recurrent myocardial infarction, heart failure, ischemic stroke, and all-cause mortality in patients with STEMI. PMID- 27381033 TI - Procalcitonin as a New Indicator of Inflammation. PMID- 27381034 TI - Nerve growth factor inhibition with tanezumab influences weight-bearing and subsequent cartilage damage in the rat medial meniscal tear model. AB - OBJECTIVE: To investigate whether the effects of nerve growth factor (NGF) inhibition with tanezumab on rats with medial meniscal tear (MMT) effectively model rapidly progressive osteoarthritis (RPOA) observed in clinical trials. METHODS: Male Lewis rats underwent MMT surgery and were treated weekly with tanezumab (0.1, 1 or 10 mg/kg), isotype control or vehicle for 7, 14 or 28 days. Gait deficiency was measured to assess weight-bearing on the operated limb. Joint damage was assessed via histopathology. A second arm, delayed onset of treatment (starting 3-8 weeks after MMT surgery) was used to control for analgesia early in the disease process. A third arm, mid-tibial amputation, evaluated the dependency of the model on weight-bearing. RESULTS: Gait deficiency in untreated rats was present 3-7 days after MMT surgery, with a return to normal weight-bearing by days 14-28. Prophylactic treatment with tanezumab prevented gait deficiency and resulted in more severe cartilage damage. When onset of treatment with tanezumab was delayed to 3-8 weeks after MMT surgery, there was no increase in cartilage damage. Mid-tibial amputation completely prevented cartilage damage in untreated MMT rats. CONCLUSIONS: These data suggest that analgesia due to NGF inhibition during the acute injury phase is responsible for increased voluntary weight bearing and subsequent cartilage damage in the rat MMT model. This model failed to replicate the hypotrophic bone response observed in tanezumab-treated patients with RPOA. PMID- 27381035 TI - Streptococcusdentiloxodontae sp. nov., isolated from the oral cavity of elephants. AB - A Gram-stain-positive, catalase-negative, coccus-shaped organism was isolated from oral cavity samples collected from healthy elephants. The isolated strain, NUM 2404T, was tentatively identified as a streptococcal species based on the results of biochemical tests. Although a comparative 16S rRNA gene sequence analysis suggested the classification of this organism into the genus Streptococcus, it did not correspond to any recognized species of the genus. Strain NUM 2404T was related most closely to Streptococcus saliviloxodontae NUM 6306T with 95.8 % 16S rRNA gene sequence similarity, but the phylogenetic tree reconstructed based on the 16S rRNA gene sequence showed that NUM 2404T clustered with Streptococcus mutans NCTC 10449T and Streptococcus troglodytae TKU 31T. Comparative sequence analysis based on two housekeeping genes, groEL, which encodes the 60 kDa heat-shock protein, and rpoB, encoding the beta subunit of RNA polymerase, of NUM 2404T indicated that it was most closely related to those of Streptococcus orisratti A63T and Streptococcus sobrinus ATCC 33478T with 82.7 and 85.1 % sequence similarities, respectively. On the basis of genotypic and phenotypic differences, it is proposed that the novel isolate be classified in the genus Streptococcus as representative of a novel species, Streptococcus dentiloxodontae sp. nov. The type strain is NUM 2404T (=JCM 19284T=DSM 27381T). PMID- 27381036 TI - Toxicity of two fungicides in Daphnia: is it always temperature-dependent? AB - The joint effect of increasing temperature and pollution on aquatic organisms is important to understand and predict, as a combination of stressors might be more noxious when compared to their individual effects. Our goal was to determine the sensitivity of a model organism (Daphnia spp.) to contaminants at increasing temperatures, allowing prior acclimation of the organisms to the different temperatures. Prior to exposure, two Daphnia genotypes (Daphnia longispina species complex) were acclimated to three temperatures (17, 20, and 23 degrees C). Afterwards, a crossed design was established using different exposure temperatures and a range of concentrations of two common fungicides (tebuconazole and copper). Daphnia life history parameters were analysed in each temperature * toxicant combination for 21 days. Temperature was the most influencing factor: Daphnia reproduced later and had lower fecundity at 17 degrees C than at 20 and 23 degrees C. Both copper and tebuconazole also significantly reduced the fecundity and survival of Daphnia at environmentally-relevant concentrations. Temperature-dependence was found for both toxicants, but the response pattern was endpoint- and genotype-specific. The combination of contaminant and high temperature often had severe effects on survival. However, unlike some literature on the subject, our results do not support the theory that increasing temperatures consistently foment increasing reproductive toxicity. The absence of a clear temperature-dependent toxicity pattern may result from the previous acclimation to the temperature regime. However, a proper framework is lacking to compare such studies and to avoid misleading conclusions for climate change scenarios. PMID- 27381037 TI - Conservation, Innovation, and Bias: Embryonic Segment Boundaries Position Posterior, but Not Anterior, Head Horns in Adult Beetles. AB - The integration of form and function of novel traits is a fundamental process during the developmental evolution of complex organisms, yet how novel traits and trait functions integrate into preexisting contexts remains poorly understood. Here, we explore the mechanisms by which the adult insect head has been able to integrate novel traits and features during its ontogeny, focusing on the cephalic horns of Onthophagus beetles. Specifically, using a microablation approach we investigate how different regions of the dorsal head of adult horned beetles relate to their larval and embryonic counterparts and test whether deeply conserved regional boundaries that establish the embryonic head might also facilitate or bias the positioning of cephalic horns along the dorsal adult head. We find that paired posterior horns-the most widespread horn type within the genus-are positioned along a border homologous to the embryonic clypeolabral (CL) ocular boundary, and that this placement constitutes the ancestral form of horn positioning. In contrast, we observed that the phylogenetically much rarer anterior horns are positioned by larval head regions contained firmly within the CL segment and away from any major preexisting larval head landmarks or boundaries. Lastly, we describe the unexpected finding that ablations at medial head regions can result in ectopic outgrowths bearing terminal structures resembling the more anterior clypeal ridge. We discuss our results in the light of the developmental genetic mechanisms of head formation in holometabolous insects and the role of co-option in innovation and bias in developmental evolution. PMID- 27381038 TI - The views of migrant health workers living in Austria and Belgium on return migration to sub-Saharan Africa. AB - BACKGROUND: The negative consequences of the brain drain of sub-Saharan African health workers for source countries are well documented and include understaffed facilities, decreased standards of care and higher workloads. However, studies suggest that, if migrated health workers eventually return to their home countries, this may lead to beneficial effects following the transfer of their acquired skills and knowledge (brain gain). The present study aims to explore the factors influencing the intentions for return migration of sub-Saharan African health workers who emigrated to Austria and Belgium, and gain further insight into the potential of circular migration. METHODS: Semi-structured interviews with 27 sub-Saharan African health workers in Belgium and Austria were conducted. RESULTS: As mentioned by the respondents, the main barriers for returning were family, structural crises in the source country, and insecurity. These barriers overrule the perceived drivers, which were nearly all pull factors and emotion driven. Despite the fact that only a minority plans to return permanently, many wish to return regularly to work in the healthcare sector or to contribute to the development of their source country. CONCLUSION: As long as safety and structural stability cannot be guaranteed in source countries, the number of return migrants is likely to remain low. National governments and regional organizations could play a role in facilitating the engagement of migrant health workers in the development of the healthcare system in source countries. PMID- 27381039 TI - MSC from fetal and adult lungs possess lung-specific properties compared to bone marrow-derived MSC. AB - Mesenchymal stromal cells (MSC) are multipotent cells with regenerative and immune-modulatory properties. Therefore, MSC have been proposed as a potential cell-therapy for bronchiolitis obliterans syndrome (BOS). On the other hand, there are publications demonstrating that MSC might be involved in the development of BOS. Despite limited knowledge regarding the functional role of tissue-resident lung-MSC, several clinical trials have been performed using MSC, particularly bone marrow (BM)-derived MSC, for various lung diseases. We aimed to compare lung-MSC with the well-characterized BM-MSC. Furthermore, MSC isolated from lung-transplanted patients with BOS were compared to patients without BOS. Our study show that lung-MSCs are smaller, possess a higher colony-forming capacity and have a different cytokine profile compared to BM-MSC. Utilizing gene expression profiling, 89 genes including lung-specific FOXF1 and HOXB5 were found to be significantly different between BM-MSC and lung-MSC. No significant differences in cytokine secretion or gene expression were found between MSC isolated from BOS patients compared recipients without BOS. These data demonstrate that lung-resident MSC possess lung-specific properties. Furthermore, these results show that MSC isolated from lung-transplanted patients with BOS do not have an altered phenotype compared to MSC isolated from good outcome recipients. PMID- 27381040 TI - An Internet-based health gateway device for interactive communication and automatic data uploading: Clinical efficacy for type 2 diabetes in a multi-centre trial. AB - Introduction The aim of this study was to improve the quality of diabetes control and evaluate the efficacy of an Internet-based integrated healthcare system for diabetes management and safety. Methods We conducted a large-scale, multi-centre, randomized clinical trial involving 484 patients. Patients in the intervention group ( n = 244) were treated with the Internet-based system for six months, while the control group ( n = 240) received the usual outpatient management over the same period. HbA1c, blood chemistries, anthropometric parameters, and adverse events were assessed at the beginning of the study, after three months, and the end of the study. Results There were no initial significant differences between the groups with respect to demographics and clinical parameters. Upon six-month follow-up, HbA1c levels were significantly decreased from 7.86 +/- 0.69% to 7.55 +/- 0.86% within the intervention group ( p < 0.001) compared to 7.81 +/- 0.66% to 7.70 +/- 0.88% within the control group. Postprandial glucose reduction was predominant. A subgroup with baseline HbA1c higher than 8% and good compliance achieved a reduction of HbA1c by 0.8 +/- 1.05%. Glucose control and waist circumference reduction were more effective in females and subjects older than 40 years of age. There were no adverse events associated with the intervention. Discussion This e-healthcare system was effective for glucose control and body composition improvement without associated adverse events in a multi-centre trial. This system may be effective in improving diabetes control in the general population. PMID- 27381041 TI - Anxiolytic-like effects and toxicological studies of Brickellia cavanillesii (Cass.) A. Gray in experimental mice models. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Brickellia cavanillesii (Asteraceae) (Cass.) A. Gray is one of the popular plants consumed in Central America and Mexico for the treatment of several diseases such as hypertension, diabetes and anxiety, among others. AIM OF THE STUDY: To determine the anxiolytic-like effect of B. Cavanillesii and the safety of its use through toxicological studies. MATERIAL AND METHODS: Anxiolytic-like effects of soluble-methanol extract of B. cavanillesii (MEBc) were evaluated in ambulatory activity (open-field test), hole board test, cylinder of exploration, the elevated plus-maze and the potentiation of the sodium pentobarbital-induced hypnosis mice models. On the other hand, in vivo toxicological studies were conducted on acute and sub-acute mice models recommended by OECD. Active MEBc was subjected to phytochemical studies through conventional chromatographic techniques to isolate bioactive compounds. RESULTS: MEBc (100mg/Kg) showed significant anxiolytic-like effect on animal model used (p<0.05). The phytochemical analysis of MEBc allowed the isolation of two major compounds nicotiflorin and acacetin, among others. Both compounds were found to be partially responsible for the anxiolytic-like effects. Moreover, a median lethal dose (LD50) higher than 2000mg/Kg was determined in mice and sub-acute oral administration of MEBc (100mg/Kg) did not alter body weight, clinical chemistry parameters (ALT and AST) and it did not induce any toxic nor alteration in the liver, kidney and heart functions. CONCLUSIONS: In current investigation, we have shown that MEBc has a wide range of pharmacology-toxicology patterns. The results support further investigation of MEBc as a potential anxiolytic phytomedicinal agent. PMID- 27381043 TI - Medical register could include voluntary conflicts of interest information. PMID- 27381042 TI - Phytochemical and biological studies on Alnus glutinosa subsp. glutinosa, A. orientalis var. orientalis and A. orientalis var. pubescens leaves. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Alnus species have been used for the treatment of rheumatism, hemorrhoids and for wound healing in folk medicine. MATERIALS AND METHODS: Aqueous and methanol extracts of A. glutinosa (L.) Gaertner subsp. glutinosa, A. orientalis Decne. var. orientalis and A. orientalis var. pubescens Dippel leaves were evaluated for their wound healing, anti-inflammatory and antioxidant activities. In vivo wound models of linear incision and circular excision were performed. "Inhibition of acetic acid-induced capillary permeability", "carrageenan-induced hind paw edema" and T"PA-induced ear edema" assays were applied to determine the anti-inflammatory effects. For the antioxidant activity assessment, DPPH and ABTS radicals scavenging effect, reducing power and denaturation of nonspecific hydroxyl radical-targeted 2 deoxyribose were used. In vitro inhibitory effects on enzymes hyaluronidase, collagenase and elastase were evaluated. The methanol extract of the leaves of A. glutinosa subsp. glutinosa (MB), the most potent extract, was fractionated by bioassay-guided fractionation technique. The structure of the isolated compound was determined as shikimic acid by using NMR and IR analyses. RESULTS: MB increased the wound tension by 42.79% value and provided a contraction by 51.58%. Wound tension, contraction capacity and tissue hydroxyproline levels were increased with the application of the fraction EtOAc: MeOH (Fr. D), subfraction D27-38 and shikimic acid. In the "inhibition of acetic acid-induced capillary permeability" assay, MB, Fr. D, subfraction D27-38 and shikimic acid inhibited the permeability with significant inhibition values of 30.22%, 32.46%, 38.24% and 27.19%, respectively. In carrageenan-induced hind paw edema model, MB displayed 29.1% inhibition. Likewise, Fr. D, subfraction D27-38, and shikimic acid were found to exhibit remarkable anti-inflammatory and antioxidant effects. Shikimic acid exhibited significant inhibitory effect (38.24%) on the hyaluronidase enzyme. CONCLUSIONS: This is the first and unique study that investigates wound healing, anti-inflammatory and antioxidant effects of some Alnus taxons growing in Turkey. According to the results, shikimic acid was found to be the major compound responsible from the activity. PMID- 27381044 TI - Use of the oral sugar test in ponies when performed with or without prior fasting. AB - BACKGROUND: It is recommended that the oral sugar test (OST) for insulin dysregulation (ID) be performed after an overnight fast, but fasting is impractical in ponies kept solely at pasture. There are few data on OST repeatability and reliability in ponies. OBJECTIVES: To report 1) whether OST results obtained in the morning after an overnight fast or without fasting in the afternoon (FASTING/FED) can be used interchangeably, 2) time of highest insulin concentration Tmax [insulin], repeatability and reliability of insulin response to the OST when FASTING or FED and 3) dichotomous agreement (ID/normal) within a small sample when FASTING or FED. STUDY DESIGN: Method comparison study. METHODS: Oral sugar tests were performed on four occasions in 10 adult native British ponies, twice FASTING and twice FED. Insulin concentrations were measured by radioimmunoassay at 0-120 min (T0,30,60,75,90,120 ). Differences between FASTING and FED results were assessed using mixed effects models. Indices of repeatability and reliability were calculated; dichotomous agreement was reported using kappa statistics. RESULTS: Serum [insulin] was significantly (P<=0.05) higher at T60 -T90 with prior fasting (estimated differences [95% confidence intervals]): T60 : 23.5 MUiu/ml (8.7-38.4 MUiu/ml), T75 : 27.1 MUiu/ml (12.3-41.8 MUiu/ml), T90 : 15.1 (0.36-29.9 MUiu/ml). Most frequently, Tmax [ins] occurred at T30 . At any single time point, within-subject coefficients of variation were: FASTING: 40% and FED: 31%. The 95% limits for repeatability were FASTING: 29 340%, FED: 41-240%. Test reliabilities were FASTING: 0.70 and FED: 0.67. For dichotomous interpretation similar results (kappa = 0.7) were obtained using cut offs of [Insulin] >60 MUiu/ml at T60 or T90 for FASTING and [Insulin] >51 MUiu/ml at T30 or T60 for FED samples. MAIN LIMITATIONS: Oral sugar tests were performed on a small number of animals on one pasture during one season (spring). CONCLUSIONS: Clinicians should beware of interpreting changes in absolute OST results owing to poor repeatability. When stabling is unavailable, OSTs of ponies at pasture may yield similar dichotomous results without prior fasting. PMID- 27381045 TI - Whole-cell detection of live lactobacillus acidophilus on aptamer-decorated porous silicon biosensors. AB - This work describes the design of optical aptamer-based porous silicon (PSi) biosensors for the direct capture of Lactobacillus acidophilus. Aptamers are oligonucleotides (single-stranded DNA or RNA) that can bind their targets with high affinity and specificity, making them excellent recognition elements for biosensing applications. Herein, aptamer Hemag1P, which specifically targets the important probiotic L. acidophilus, was utilized for direct bacteria capture onto oxidized PSi Fabry-Perot thin films. Monitoring changes in the reflectivity spectrum (using reflective interferometric Fourier transform spectroscopy) allows for bacteria detection in a label-free, simple and rapid manner. The performance of the biosensor was optimized by tuning the PSi nanostructure, its optical properties, as well as the immobilization density of the aptamer. We demonstrate the high selectivity and specificity of this simple "direct-capture" biosensing scheme and show its ability to distinguish between live and dead bacteria. The resulting biosensor presents a robust and rapid method for the specific detection of live L. acidophilus at concentrations relevant for probiotic products and as low as 10(6) cells per mL. Rapid monitoring of probiotic bacteria is crucial for quality, purity and safety control as the use of probiotics in functional foods and pharmaceuticals is becoming increasingly popular. PMID- 27381046 TI - Roseomonas rubra sp. nov., isolated from lagoon sediments. AB - A novel Gram-stain-negative, coccus to oval-shaped, non-motile bacterium, designated strain S5T, was isolated from lagoon sediments collected from North Carolina, USA. Strain S5T was able to grow at 12-45 degrees C (optima, 30-37 degrees C) and at pH 6.3-9.0 (optima, 6.5-7.5). No added NaCl was required for growth of strain S5T. Strain S5T was positive for catalase and oxidase activity. C18 : 1omega6c/C18 : 1omega7c, C16 : 1omega6c/C16 : 1omega7c and C16 : 0 were predominant fatty acids with minor amounts of C8 : 0 3-OH, C14 : 0, C16 : 0 3-OH, C18 : 1 2-OH, C14 : 1omega5c, C16 : 1omega5c and C19 : 0 cyclo omega8c. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and an unidentified glycolipid were major polar lipids. Minor amounts of an unidentified amino lipid and three unidentified lipids were also detected. The G+C content of the genomic DNA was 73.5 mol%. 16S rRNA gene sequence comparisons indicated that strain S5T represents a member of the genus Roseomonas within the family Acetobacteraceae of the class Alphaproteobacteria. Strain S5T had a sequence similarity of 97.80 % with Roseomonas rhizosphaerae YW11T, 97.69 % with Roseomonas aestuarii JC17T and <97 % with other members of the genus Roseomonas. However, strain S5T showed only 45.2+/-2 and 17+/-2 % relatedness (based on DNA-DNA hybridization) with R. rhizosphaerae KACC 17225T (=YW11T) and R. aestuarii KCTC 22692T (=JC17T), respectively. Distinct morphological, physiological and genotypic differences from previously described taxa support the classification of strain S5T as a representative of a novel species in the genus Roseomonas, for which the name Roseomonas rubra sp. nov. is proposed. The type strain is S5T (=KEMB 563-468T=JCM 31177T). PMID- 27381047 TI - Exploring longitudinal shifts in international nurse migration to the United States between 2003 and 2013 through a random effects panel data analysis. AB - BACKGROUND: No study has examined the longitudinal trends in National Council Licensure Exam for Registered Nurse (NCLEX-RN) applicants and pass rates among internationally-educated nurses (IENs) seeking to work in the United States, nor has any analysis explored the impact of specific events on these trends, including changes to the NCLEX-RN exam, the role of the economic crisis, or the passing of the WHO Code on the International Recruitment of Health Personnel. This study seeks to understand the impact of the three aforementioned factors that may be influencing current and future IEN recruitment patterns in the United States. METHODS: In this random effects panel data analysis, we analyzed 11 years (2003-2013) of annual IEN applicant numbers and pass rates for registered nurse credentialing. Data were obtained from publicly available reports on exam pass rates. With the global economic crisis and NCLEX-RN changes in 2008 coupled with the WHO Code passage in 2010, we sought to compare if (1) the number of applicants changed significantly after those 2 years and (2) if pass rates changed following exam modifications implemented in 2008 and 2011. RESULTS: A total of 177 countries were eligible for inclusion in this analysis, representing findings from 200,453 IEN applicants to the United States between 2003 and 2013. The majority of applicants were from the Philippines (58 %) and India (11 %), with these two countries combined representing 69 % of the total. Candidates from Sub-Saharan African countries totalled 7133 (3 % of all applications) over the study period, with half of these coming from Nigeria alone. No significant changes were found in the number of candidates following the 2008 economic crisis or the 2010 WHO Code, although pass rates decreased significantly following the 2008 exam modifications and the WHO Code implementation. CONCLUSION: This study suggests that, while the WHO Code has had an influence on overall IEN migration dynamics to the United States by decreasing candidate numbers, in most cases, the WHO Code was not the single cause of these fluctuations. Indeed, the impact of the NCLEX-RN exam changes appears to exert a larger influence. PMID- 27381049 TI - Enhanced Electrocatalytic Performance of a Porous g-C3 N4 /Graphene Composite as a Counter Electrode for Dye-Sensitized Solar Cells. AB - A porous graphitic carbon nitride (g-C3 N4 )/graphene composite was prepared by a simple hydrothermal method and explored as the counter electrode of dye sensitized solar cells (DSCs). The obtained g-C3 N4 /graphene composite was characterized by XRD, SEM, TEM, FTIR spectroscopy, and X-ray photoelectron spectroscopy. The results show that incorporating graphene nanosheets into g-C3 N4 forms a three-dimensional architecture with a high surface area, porous structure, efficient electron-transport network, and fast charge-transfer kinetics at the g-C3 N4 /graphene interfaces. These properties result in more electrocatalytic active sites and facilitate electrolyte diffusion and electron transport in the porous framework. As a result, the as-prepared porous g-C3 N4 /graphene composite exhibits an excellent electrocatalytic activity. In I(-) /I3 (-) redox electrolyte, the charge-transfer resistance of the porous g-C3 N4 /graphene composite electrode is 1.8 Omega cm(2) , which is much lower than those of individual g-C3 N4 (70.1 Omega cm(2) ) and graphene (32.4 Omega cm(2) ) electrodes. This enhanced electrocatalytic performance is beneficial for improving the photovoltaic performance of DSCs. By employing the porous g-C3 N4 /graphene composite as the counter electrode, the DSC achieves a conversion efficiency of 7.13 %. This efficiency is comparable to 7.37 % for a cell with a platinum counter electrode. PMID- 27381048 TI - Intracellular cholesterol transport proteins enhance hydrolysis of HDL-CEs and facilitate elimination of cholesterol into bile. AB - While HDL-associated unesterified or free cholesterol (FC) is thought to be rapidly secreted into the bile, the fate of HDL-associated cholesteryl esters (HDL-CEs) that represent >80% of HDL-cholesterol, is only beginning to be understood. In the present study, we examined the hypothesis that intracellular cholesterol transport proteins [sterol carrier protein 2 (SCP2) and fatty acid binding protein-1 (FABP1)] not only facilitate CE hydrolase-mediated hydrolysis of HDL-CEs, but also enhance elimination of cholesterol into bile. Adenovirus mediated overexpression of FABP1 or SCP2 in primary hepatocytes significantly increased hydrolysis of HDL-[(3)H]CE, reduced resecretion of HDL-CE-derived FC as nascent HDL, and increased its secretion as bile acids. Consistently, the flux of [(3)H]cholesterol from HDL-[(3)H]CE to biliary bile acids was increased by overexpression of SCP2 or FABP1 in vivo and reduced in SCP2(-/-) mice. Increased flux of HDL-[(3)H]CE to biliary FC was noted with FABP1 overexpression and in SCP2(-/-) mice that have increased FABP1 expression. Lack of a significant decrease in the flux of HDL-[(3)H]CE to biliary FC or bile acids in FABP1(-/-) mice indicates the likely compensation of its function by an as yet unidentified mechanism. Taken together, these studies demonstrate that FABP1 and SCP2 facilitate the preferential movement of HDL-CEs to bile for final elimination. PMID- 27381050 TI - Pharmacogenomics and the treatment of acute myeloid leukemia. AB - Acute myeloid leukemia (AML) is a clinically and biologically heterogeneous malignancy that is primarily treated with combinations of cytarabine and anthracyclines. Although this scheme remains effective in most of the patients, variability of outcomes in patients has been partly related with their genetic variability. Several pharmacogenetic studies have analyzed the impact of polymorphisms in genes encoding transporters, metabolizers or molecular targets of chemotherapy agents. A systematic review on all eligible studies was carried out in order to estimate the effect of polymorphisms of anthracyclines and cytarabine pathways on efficacy and toxicity of AML treatment. Other emerging genes recently studied in AML, such as DNA repair genes, genes potentially related to chemotherapy response or AML prognosis, have also been included. PMID- 27381051 TI - Pancreatic polypeptide stimulates mouse gastric motor activity through peripheral neural mechanisms. AB - BACKGROUND: Pancreatic polypeptide (PP) is supposed to be one of the major endogenous agonists of the neuropeptide Y4 receptor. Pancreatic polypeptide can influence gastrointestinal motility, acting mainly through vagal mechanisms, but whether PP acts directly on the stomach has not been explored yet. The aims of this study were to investigate the effects of PP on mouse gastric emptying, on spontaneous tone of whole stomach in vitro and to examine the mechanism of action. METHODS: Gastric emptying was measured by red phenol method after i.p. PP administration (1-3 nmol per mouse). Responses induced by PP (1-300 mmol L-1 ) on gastric endoluminal pressure were analyzed in vitro in the presence of different drugs. Gastric genic expression of Y4 receptor was verified by RT-PCR. KEY RESULTS: Pancreatic polypeptide dose-dependently increased non-nutrient liquid gastric emptying rate. In vitro, PP produced a concentration-dependent contraction that was abolished by tetrodotoxin, a neural blocker of Na+ voltage dependent channels. The contractile response was significantly reduced by atropine, a muscarinic receptor antagonist, and by SR48968, an NK2 receptor antagonist, while it was potentiated by neostigmine, an inhibitor of acetylcholinesterase. The joint application of atropine and SR48968 fully abolished PP contractile effect. Reverse transcriptase-polymerase chain reaction analysis revealed the presence of Y4 receptor mRNA in mouse stomach with a greater expression in antrum than in fundus. CONCLUSIONS & INFERENCES: The present findings demonstrate that exogenous PP stimulates mouse gastric motor activity, by acting directly on the stomach. This effect appears due to the activation of enteric excitatory neurons releasing acetylcholine and tachykinins. PMID- 27381052 TI - Tetrahydropyrrolization of Resveratrol and Other Stilbenes Improves Inhibitory Effects on DNA Oxidation. AB - The inhibitory effect of resveratrol on DNA oxidation caused by 2,2'-azobis(2 amidinopropane hydrochloride) (AAPH) was found to be enhanced if the C=C bond in resveratrol was converted into tetrahydropyrrole by reaction with azomethine ylide (CH2 =N(+) (CH3 )CH2 (-) ). This encouraged us to explore whether the inhibitory activities of other stilbenes could also be increased by the same method. We found that the inhibitory effects of the tetrahydropyrrole derivatives on AAPH-induced oxidation of DNA were higher than those of the corresponding stilbenes, because the tetrahydropyrrole motif can provide hydrogen atoms to be abstracted by radicals. Therefore, the tetrahydropyrrolization offered an advantage for enhancing the antioxidant effects of stilbenes. Notably, (CH3 )3 SiCH2 N(CH3 )CH2 OCH3 (in the presence of CF3 COOH) and (CH3 )3 NO (in the presence of LiN(iPr)2 ) can be used to generate azomethine ylide for the tetrahydropyrrolization of stilbenes containing electron-withdrawing and donating groups, respectively. PMID- 27381053 TI - Surgical management of a complete section of the oesophagus during total thyroidectomy. PMID- 27381054 TI - Convergence in relationships between leaf traits, spectra and age across diverse canopy environments and two contrasting tropical forests. AB - Leaf age structures the phenology and development of plants, as well as the evolution of leaf traits over life histories. However, a general method for efficiently estimating leaf age across forests and canopy environments is lacking. Here, we explored the potential for a statistical model, previously developed for Peruvian sunlit leaves, to consistently predict leaf ages from leaf reflectance spectra across two contrasting forests in Peru and Brazil and across diverse canopy environments. The model performed well for independent Brazilian sunlit and shade canopy leaves (R2 = 0.75-0.78), suggesting that canopy leaves (and their associated spectra) follow constrained developmental trajectories even in contrasting forests. The model did not perform as well for mid-canopy and understory leaves (R2 = 0.27-0.29), because leaves in different environments have distinct traits and trait developmental trajectories. When we accounted for distinct environment-trait linkages - either by explicitly including traits and environments in the model, or, even better, by re-parameterizing the spectra-only model to implicitly capture distinct trait-trajectories in different environments - we achieved a more general model that well-predicted leaf age across forests and environments (R2 = 0.79). Fundamental rules, linked to leaf environments, constrain the development of leaf traits and allow for general prediction of leaf age from spectra across species, sites and canopy environments. PMID- 27381055 TI - "Calibration-on-the-spot": How to calibrate an EMCCD camera from its images. AB - In order to count photons with a camera, the camera must be calibrated. Photon counting is necessary, e.g., to determine the precision of localization-based super-resolution microscopy. Here we present a protocol that calibrates an EMCCD camera from information contained in isolated, diffraction-limited spots in any image taken by the camera, thus making dedicated calibration procedures redundant by enabling calibration post festum, from images filed without calibration information. PMID- 27381057 TI - Computer-Aided Diagnosis of Different Rotator Cuff Lesions Using Shoulder Musculoskeletal Ultrasound. AB - The lifetime prevalence of shoulder pain approaches 70%, which is mostly attributable to rotator cuff lesions such as inflammation, calcific tendinitis and tears. On clinical examination, shoulder ultrasound is recommended for the detection of lesions. However, there exists inter-operator variability in diagnostic accuracy because of differences in the experience and expertise of operators. In this study, a computer-aided diagnosis (CAD) system was developed to assist ultrasound operators in diagnosing rotator cuff lesions and to improve the practicality of ultrasound examination. The collected cases included 43 cases of inflammation, 30 cases of calcific tendinitis and 26 tears. For each case, the lesion area and texture features were extracted from the entire lesions and combined in a multinomial logistic regression classifier for lesion classification. The proposed CAD achieved an accuracy of 87.9%. The individual accuracy of this CAD system was 88.4% for inflammation, 83.3% for calcific tendinitis and 92.3% for tears. Cohen's k was 0.798. On the basis of its diagnostic performance, clinical use of this CAD technique has promise. PMID- 27381056 TI - Curcumin ameliorates neuropathic pain by down-regulating spinal IL-1beta via suppressing astroglial NALP1 inflammasome and JAK2-STAT3 signalling. AB - Curcumin has been shown to possess strong anti-inflammatory activity in many diseases. It has been demonstrated that the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) cascade and the NAcht leucine rich-repeat protein 1 (NALP1) inflammasome are important for the synthesis of Pro Interleukin (IL)-1beta and the processing of the inactive protein to its mature form, which plays an active role in the pathogenesis of neuropathic pain. The present study showed that repeated intraperitoneal injection of curcumin ameliorated SNI-induced mechanical and cold allodynia in a dose-dependent manner and inhibited the elevation of spinal mature IL-1beta protein levels. Additionally, repeated curcumin treatment significantly inhibited the aggregation of the NALP1 inflammasome and the activation of the JAK2-STAT3 cascade in spinal astrocytes. Furthermore, the genetic down-regulation of NALP1 inflammasome activation by NALP1 siRNA and the pharmacological inhibition of the JAK2-STAT3 cascade by AG490 markedly inhibited IL-1beta maturation and Pro-IL-1beta synthesis, respectively, and reduced SNI-induced pain hypersensitivity. Our results suggest that curcumin attenuated neuropathic pain and down-regulated the production of spinal mature IL-1beta by inhibiting the aggregation of NALP1 inflammasome and the activation of the JAK2-STAT3 cascade in astrocytes. PMID- 27381058 TI - Drug use and its associated factors among money boys in Hunan Province, China. AB - OBJECTIVES: To describe drug use, types of drugs and related factors among money boys in Hunan Province, China. STUDY DESIGN: A cross-sectional study was conducted between July 2012 and January 2013. METHODS: Based on respondent-driven sampling, researchers located seven 'seeds' via a gay-dating website: http://www.ixxqy.org. After three waves of recruitment, 234 money boys were enrolled. They were asked to complete a 23-item questionnaire regarding demographic characteristics, drug use, a history of human immunodeficiency virus infection and family environment. Descriptive statistics and logistic regression analysis were conducted using Statistical Package for the Social Sciences Version 20.0. RESULTS: In total, 205 valid questionnaires were collected. Based on the data collected, 80 (39.0%) money boys had used drugs within the last 3 months. Rush popper (36.6%) and methamphetamine (12.7%) were used most commonly, and other drugs used were ecstasy (7.8%), ketamine (5.9%), marijuana (2.4%), morphine (1.5%), heroin (1.0%) and cocaine (0.5%). Factors included in the logistic regression were length of service (odds ratio [OR] 0.395, 95% confidence interval [CI] 0.175-0.896), being an only child (OR 2.272, 95% CI 1.108-4.659), relationship between parents (OR 0.428, 95% CI 0.213-0.858) and social network (OR 2.387, 95% CI 1.144-4.970). A shorter length of service and a good relationship between parents were protective factors against drug use, while being an only child and having a wide social network were risk factors. CONCLUSION: Drug use is common among money boys. This study found that length of service, being an only child, relationship between parents and social network are associated with drug use. PMID- 27381059 TI - Consequences of simulated car driving at constant high speed on the sensorimotor control of leg muscles and the braking response. AB - Due to the increase in time spent seated in cars, there is a risk of fatigue of the leg muscles which adjust the force exerted on the accelerator pedal. Any change in their sensorimotor control could lengthen the response to emergency braking. Fourteen healthy male subjects (mean age: 42 +/- 4 years) were explored. Before and after a 1-h driving trial at 120 km h-1 , we measured the braking response, the maximal leg extension and foot inversion forces, the tonic vibratory response (TVR) in gastrocnemius medialis (GM) and tibialis anterior (TA) muscles to explore the myotatic reflex, and the Hoffmann reflex (H-reflex). During driving, surface electromyograms (EMGs) of GM and TA were recorded and the ratio between high (H) and low (L) EMG energies allowed to evaluate the recruitment of high- and low-frequency motor unit discharges. During driving, the H/L ratio decreased in TA, whereas modest and often no significant H/L changes occurred in GM muscle. After driving, the maximal foot inversion force decreased (-19%), while the leg extension force did not vary. Reduced TVR amplitude (-29%) was measured in TA, but no H-reflex changes were noted. The braking reaction time was not modified after the driving trial. Driving at constant elevated speed reduced the myotatic reflex and the recruitment of motor units in TA muscle. The corresponding changes were rarely present in the GM muscle that plays a key role in the braking response, and this could explain the absence of a reduced braking reaction time. PMID- 27381060 TI - Dialysis buffer with different ionic strength affects the antigenicity of cultured nervous necrosis virus (NNV) suspensions. AB - Nervous necrosis virus (NNV) belongs to the genus Betanodavirus (Nodaviridae). It is highly pathogenic to various marine fishes. Here, we investigated the antigenicity changes of cultured NNV suspensions during 14days of dialyses using a dialysis tube at 1.4*10(4) molecular weight cut off (MWCO) in three different buffers (Dulbecco's phosphate buffered saline (D-PBS), 15mM Tris-HCl (pH 8.0), and deionized water (DIW)). Total NNV antigen titers of cultured NNV suspension varied depending on different dialysis buffers. For example, total NNV antigen titer during D-PBS dialysis was increased once but then decreased. During Tris HCl dialysis, it was relatively stable. During dialysis in DIW, total NNV antigen titer was increased gradually. These antigenicity changes in NNV suspension might be due to changes in the aggregation state of NNV particles and/or coat proteins (CPs). ELISA values of NNV suspension changed due to changing aggregates state of NNV antigens. NNV particles in suspension were aggregated at a certain level. These aggregates were progressive after D-PBS dialysis, but regressive after Tris HCl dialysis. The purified NNV particles self-aggregated after dialysis in D-PBS or in Tris-HCl containing 600mM NaCl, but not after dialysis in Tris-HCl or DIW. Quantitative analysis is merited to determine NNV antigens in the highly purified NNV particles suspended in buffer at low salt condition. PMID- 27381061 TI - Early dengue virus interactions: the role of dendritic cells during infection. AB - Dengue is an acute infectious disease caused by dengue virus (DENV) that affects approximately 400 million people annually, being the most prevalent human arthropod-borne disease. DENV infection causes a wide variety of clinical manifestations that range from asymptomatic to dengue fever, and in some cases may evolve to the more severe dengue hemorrhagic fever and dengue shock syndrome. The exact reasons why some patients do not have symptoms while others develop the severe forms of disease are still elusive, but gathered evidence showed correlation between a secondary infection with a heterologous DENV serotype and the occurrence of severe symptoms. Despite several advances, the mechanisms of DENV infection are still not completely elucidated, and efforts have been made to understand the development of immunity and/or pathology to DENV. When a mosquito transmits DENV, the virus is initially deposited in the skin, where mononuclear phagocytic cells, such as dendritic cells (DCs), become infected. DCs play a critical role in the induction of immune responses, as they are able to rapidly detect pathogen-associated molecular patterns, endocytose and process antigens, and efficiently activate naive-T and B cells. Recent findings have shown that DCs serve as DENV targets, but they are also important mediators of immunity against the virus. In this review, we will briefly discuss DENV infection pathogenesis, and introduce DCs as central players in the induction of anti-DENV immune responses. Then, we will review in more detail how DENV interacts with and is sensed by DCs, with particular emphasis in two classes of receptors implicated in viral entry. PMID- 27381062 TI - Copper oxide nanoparticles in an epoxy network: microstructure, chain confinement and mechanical behaviour. AB - Copper oxide nanoparticles (nCOPs) having octahedral morphology, synthesized through hydrazine reduction reaction were employed to formulate an epoxy based novel nanocomposite. The synthesis of copper oxide nanoparticles was carried out in polyethylene glycol medium to enhance their interfacial adhesion with the epoxy matrix. The extent of conservation of the crystalline nature and octahedral morphology of the nCOP in its epoxy nanocomposites was confirmed by X-ray diffraction and electron microscopy analysis. The mechanical properties including tensile, impact, fracture toughness and surface hardness of epoxy-nCOP nanocomposites were evaluated as a function of nCOP content. The maximum enhancement in strength, modulus, impact strength, fracture toughness and surface hardness of epoxy-nCOP nanocomposites was observed for 5 phr nCOP content. This may be due to the strong interaction between the nCOP and epoxy chains at this composition arising from its fairly uniform dispersion. A quantitative measurement of constrained epoxy chains immobilized by the nCOP octahedra was carried out using dynamic mechanical analysis. The enhancement in the storage modulus is related to the amount of the added nCOP as well as the volume of the constrained epoxy chains in the proximity of nCOP. The behaviour of epoxy-nCOP nanocomposites in this study has been explained by proposing a mechanism based on the distribution of nCOP domains in the epoxy matrix and the existing volume of constrained epoxy chains. PMID- 27381063 TI - In Focus in HCB. PMID- 27381064 TI - Serological detection of 'Candidatus Liberibacter asiaticus' in citrus, and identification by GeLC-MS/MS of a chaperone protein responding to cellular pathogens. AB - We describe experiments with antibodies against 'Candidatus Liberibacter asiaticus used to detect the pathogen in infected plants. We used scFv selected to bind epitopes exposed on the surface of the bacterium in tissue prints, with secondary monoclonal antibodies directed at a FLAG epitope included at the carboxyl end of the scFv. Unexpectedly, the anti-FLAG secondary antibody produced positive results with CaLas diseased samples when the primary scFv were not used. The anti-FLAG monoclonal antibody (Mab) also identified plants infected with other vascular pathogens. We then identified a paralogous group of secreted chaperone proteins in the HSP-90 family that contained the amino acid sequence DDDDK identical to the carboxy-terminal sequence of the FLAG epitope. A rabbit polyclonal antibody against one of the same epitopes combined with a goat anti rabbit secondary antibody produced very strong purple color in individual phloem cells, as expected for this pathogen. These results were entirely specific for CaLas-infected citrus. The simplicity, cost and ability to scale the tissue print assay makes this an attractive assay to complement PCR-based assays currently in use. The partial FLAG epitope may itself be useful as a molecular marker for the rapid screening of citrus plants for the presence of vascular pathogens. PMID- 27381065 TI - Carcinoma of Gall bladder with distant metastasis to breast parenchyma. Report of a case and review of literature. AB - BACKGROUND: Gall bladder carcinoma is one of the most common cancers in India. Gall bladder cancer with metastasis to the breast is very rare. Herein we intend to report a case of carcinoma gall bladder with breast metastasis and a short review of the literature. METHODS: This report describes an interesting and unusual case of gall bladder carcinoma presenting with breast metastasis. CASE REPORT: A 38-year lady presented with complaints of right abdominal pain. Bilateral breast examination showed 2*2cm palpable lump in the upper outer quadrant of the left breast. Contrast-enhanced CT of the abdomen and pelvis showed circumferential thickening of gall bladder with the loss of fat plane with the adjacent liver parenchyma. Biopsy from the breast lump was reported as metastatic adenocarcinoma compatible with primary in the gall bladder. Whole body PET-CT showed gall bladder mass with abdominal and pelvic nodes with metastasis to liver, left breast, C7 vertebral body and left supra-clavicular node. She was diagnosed to have disseminated carcinoma gall bladder with liver, breast and supraclavicular nodal metastasis. She received palliative chemotherapy with gemcitabine and carboplatin and radiotherapy to C7 vertebra. After receiving 3 cycles of chemotherapy, chemotherapy was changed to the second line with single agent capecitabine. In spite of two lines of chemotherapy, she succumbed to disease progression and expired. CONCLUSION: There are limited examples of gall bladder adenocarcinoma with simultaneous metastasis to breast in the English literature. Our case showed an unusual dissemination of gall bladder cancer. PMID- 27381066 TI - Span poly-L-arginine nanoparticles are efficient non-viral vectors for PRPF31 gene delivery: An approach of gene therapy to treat retinitis pigmentosa. AB - Retinitis pigmentosa (RP) is the most common cause of inherited blindness in adults. Mutations in the PRPF31 gene produce autosomal dominant RP (adRP). To date there are no effective treatments for this disease. The purpose of this study was to design an efficient non-viral vector for human PRPF31 gene delivery as an approach to treat this form of adRP. Span based nanoparticles were developed to mediate gene transfer in the subretinal space of a mouse model of adRP carrying a point mutation (A216P) in the Prpf31 gene. Funduscopic examination, electroretinogram, optomotor test and optical coherence tomography were conducted to further in vivo evaluate the safety and efficacy of the nanosystems developed. Span-polyarginine (SP-PA) nanoparticles were able to efficiently transfect the GFP and PRPF31 plasmid in mice retinas. Statistically significant improvement in visual acuity and retinal thickness were found in Prpf31A216P/+ mice treated with the SP-PA-PRPF31 nanomedicine. PMID- 27381067 TI - Neutrophil targeted nano-drug delivery system for chronic obstructive lung diseases. AB - The success of drug delivery to target airway cell(s) remains a significant challenge due to the limited ability of nanoparticle (NP) systems to circumvent protective airway-defense mechanisms. The size, density, surface and physical chemical properties of nanoparticles are the key features that determine their ability to navigate across the airway-barrier. We evaluated here the efficacy of a PEGylated immuno-conjugated PLGA-nanoparticle (PINP) to overcome this challenge and selectively deliver drug to specific inflammatory cells (neutrophils). We first characterized the size, shape, surface-properties and neutrophil targeting using dynamic laser scattering, transmission electron microscopy and flow cytometry. Next, we assessed the efficacy of neutrophil-targeted PINPs in transporting through the airway followed by specific binding and release of drug to neutrophils. Finally, our results demonstrate the efficacy of PINP mediated non-steroidal anti-inflammatory drug-(ibuprofen) delivery to neutrophils in murine models of obstructive lung diseases, based on its ability to control neutrophilic-inflammation and resulting lung disease. PMID- 27381070 TI - Sulfur-Doped Fe/N/C Nanosheets as Highly Efficient Electrocatalysts for Oxygen Reduction Reaction. AB - The high-temperature pyrolyzed Fe/N/C is one of the tremendous potential nonprecious metal electrocatalysts for oxygen reduction reaction (ORR). Metal free carbon materials doped with heteroatoms have also demonstrated prominent electrocatalytic performance for ORR. The previous work of S-doping Fe/N/C was produced by pyrolyzing melamine and iron thiocyanate, in which S was from iron thiocyanate. Here, for the first time, we realized an in situ S-doping in Fe/N/C (denoted as S-Fe/N/C) electrocatalyst with S doping reaching 4.76 at % by pyrolyzing thiourea as the S source and iron acetate showing high-performance ORR activity in both alkaline and acid solution. The catalyst pyrolyzed at 700 degrees C and the mass ratio 1:0.2 shows the best activity for ORR. The optimal catalyst displays much greater durability and higher tolerance to methanol than Pt/C (20 wt %). Results of electrochemical measurements show that the S-Fe/N/C follows 4e pathway in alkaline and acid conditions. PMID- 27381068 TI - Gold nanorods inhibit respiratory syncytial virus by stimulating the innate immune response. AB - Respiratory syncytial virus (RSV) causes severe pneumonia and bronchiolitis in infants, children and older adults. The use of metallic nanoparticles as potential therapeutics is being explored against respiratory viruses like Influenza, Parainfluenza and Adenovirus. In this study, we showed that gold nanorods (GNRs) inhibit RSV in HEp-2 cells and BALB/c mice by 82% and 56%, respectively. The RSV inhibition correlated with marked upregulated antiviral genes due to GNR mediated TLR, NOD-like receptor and RIG-I-like receptor signaling pathways. Transmission electron microscopy of lungs showed GNRs in the endocytotic vesicles and histological analyses indicated infiltration by neutrophils, eosinophils and monocytes correlating with clearance of RSV. In addition, production of cytokines and chemokines in the lungs indicates recruitment of immune cells to counter RSV replication. To our knowledge, this is the first in vitro and in vivo report that provides possible antiviral mechanisms of GNRs against RSV. PMID- 27381069 TI - Enrichment of arbuscular mycorrhizal fungi in a contaminated soil after rehabilitation. AB - Spore counts, species composition and richness of arbuscular mycorrhizal fungi, and soil glomalin contents were evaluated in a soil contaminated with Zn, Cu, Cd and Pb after rehabilitation by partial replacement of the contaminated soil with non-contaminated soil, and by Eucalyptus camaldulensis planting with and without Brachiaria decumbens sowing. These rehabilitation procedures were compared with soils from contaminated non-rehabilitated area and non-contaminated adjacent soils. Arbuscular mycorrhizal fungi communities attributes were assessed by direct field sampling, trap culture technique, and by glomalin contents estimate. Arbuscular mycorrhizal fungi was markedly favored by rehabilitation, and a total of 15 arbuscular mycorrhizal fungi morphotypes were detected in the studied area. Species from the Glomus and Acaulospora genera were the most common mycorrhizal fungi. Number of spores was increased by as much as 300-fold, and species richness almost doubled in areas rehabilitated by planting Eucalyptus in rows and sowing B. decumbens in inter-rows. Contents of heavy metals in the soil were negatively correlated with both species richness and glomalin contents. Introduction of B. decumbens together with Eucalyptus causes enrichment of arbuscular mycorrhizal fungi species and a more balanced community of arbuscular mycorrhizal fungi spores in contaminated soil. PMID- 27381071 TI - Canada: Focus on a country's health system with provincial diversity. PMID- 27381072 TI - Viral hepatitis: A lack of hepatocyte STING favours HBV infection. PMID- 27381073 TI - Gut microbiota: First steps in the infant gut microbiota. PMID- 27381074 TI - Respiratory disease and the oesophagus: reflux, reflexes and microaspiration. AB - Gastro-oesophageal reflux is associated with a wide range of respiratory disorders, including asthma, isolated chronic cough, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease and cystic fibrosis. Reflux can be substantial and reach the proximal margins of the oesophagus in some individuals with specific pulmonary diseases, suggesting that this association is more than a coincidence. Proximal oesophageal reflux in particular has led to concern that microaspiration might have an important, possibly even causal, role in respiratory disease. Interestingly, reflux is not always accompanied by typical reflux symptoms, such as heartburn and/or regurgitation, leading many clinicians to empirically treat for possible gastro-oesophageal reflux. Indeed, costs associated with use of acid suppressants in pulmonary disease far outweigh those in typical GERD, despite little evidence of therapeutic benefit in clinical trials. This Review comprehensively examines the possible mechanisms that might link pulmonary disease and oesophageal reflux, highlighting the gaps in current knowledge and limitations of previous research, and helping to shed light on the frequent failure of antireflux treatments in pulmonary disease. PMID- 27381075 TI - Current management of the gastrointestinal complications of systemic sclerosis. AB - Systemic sclerosis is a multisystem autoimmune disorder that involves the gastrointestinal tract in more than 90% of patients. This involvement can extend from the mouth to the anus, with the oesophagus and anorectum most frequently affected. Gut complications result in a plethora of presentations that impair oral intake and faecal continence and, consequently, have an adverse effect on patient quality of life, resulting in referral to gastroenterologists. The cornerstones of gastrointestinal symptom management are to optimize symptom relief and monitor for complications, in particular anaemia and malabsorption. Early intervention in patients who develop these complications is critical to minimize disease progression and improve prognosis. In the future, enhanced therapeutic strategies should be developed, based on an ever-improving understanding of the intestinal pathophysiology of systemic sclerosis. This Review describes the most commonly occurring clinical scenarios of gastrointestinal involvement in patients with systemic sclerosis as they present to the gastroenterologist, with recommendations for the suggested assessment protocol and therapy in each situation. PMID- 27381076 TI - Brain stimulation during an afternoon nap boosts slow oscillatory activity and memory consolidation in older adults. AB - Sleep-related consolidation of declarative memories, as well as associated neurophysiological events such as slow oscillatory and spindle activity, deteriorate in the course of aging. This process is accelerated in neurodegenerative disease. Transcranial slow oscillatory stimulation (so-tDCS) during sleep has been shown to enhance slow oscillatory brain activity and thereby improve memory consolidation in young subjects. Here, we investigated whether so-tDCS applied to older adults during an afternoon nap exerts similar effects. Eighteen older human subjects were assessed using visuo-spatial (picture memory, primary, and location memory) and verbal memory tasks before and after a 90-min nap either comprising weak so-tDCS at 0.75Hz over fronto-central location or sham (no) stimulation in a within-subject design. Electroencephalographic activity was recorded throughout the naps and immediate effects of stimulation on brain activity were evaluated. Here, spectral power within three frequency bands of interest were computed, i.e., slow oscillatory activity, slow spindle and fast spindle activity; in 1-min stimulation-free intervals following 5 stimulation blocks. So-tDCS significantly increased frontal slow oscillatory activity as well as fast spindle activity, and significantly improved picture memory retention after sleep. Retention in the location memory subtask and in the verbal memory task was not affected. These findings may indicate a novel strategy to counteract cognitive decline in aging in a convenient manner during brief daytime naps. PMID- 27381077 TI - Instantiated mixed effects modeling of Alzheimer's disease markers. AB - The assessment and prediction of a subject's current and future risk of developing neurodegenerative diseases like Alzheimer's disease are of great interest in both the design of clinical trials as well as in clinical decision making. Exploring the longitudinal trajectory of markers related to neurodegeneration is an important task when selecting subjects for treatment in trials and the clinic, in the evaluation of early disease indicators and the monitoring of disease progression. Given that there is substantial intersubject variability, models that attempt to describe marker trajectories for a whole population will likely lack specificity for the representation of individual patients. Therefore, we argue here that individualized models provide a more accurate alternative that can be used for tasks such as population stratification and a subject-specific prognosis. In the work presented here, mixed effects modeling is used to derive global and individual marker trajectories for a training population. Test subject (new patient) specific models are then instantiated using a stratified "marker signature" that defines a subpopulation of similar cases within the training database. From this subpopulation, personalized models of the expected trajectory of several markers are subsequently estimated for unseen patients. These patient specific models of markers are shown to provide better predictions of time-to-conversion to Alzheimer's disease than population based models. PMID- 27381078 TI - Understanding the biology of the Plasmodium falciparum apicoplast; an excellent target for antimalarial drug development. AB - Malaria is a life-threatening tropical disease, caused by the intracellular parasite Plasmodium falciparum. The World Health Organization counts malaria as one of the top ten causes of worldwide death. The unavailability of a successful malaria vaccine and the ever-increasing instances of drug resistance in the malaria parasite demand the discovery of new targets within P. falciparum for the development of next generation antimalarials. Fortunately, all apicomplexan parasites, including P. falciparum harbor a relict, non-photosynthetic plastid known as the apicoplast. The apicoplast is a semi-autonomous organelle within P. falciparum containing a 35kb circular genome. Despite a genome of its own, majority of the apicoplast proteins are encoded by the parasite nucleus and imported into the apicoplast. The organelle has been shown to be essential to P. falciparum survival and the loss the apicoplast manifests as a 'delayed death' response in the parasite. The apicoplast has evolved out of cyanobacteria in a complex, two step endosymbiotic event. As a result the architecture and the gene expression machinery of the apicoplast is quite bacteria-like and is susceptible to a wide range of antibiotics such as fosmidomycin, tetracycline, azithromycin, clindamycin and triclosan. The biosynthetic pathways for isoprenoids, fatty acids and heme operate within the malaria apicoplast, making the organelle an excellent target for drug development. The review focuses on the evolution, biology and the essentiality of the apicoplast within the malaria parasite and discusses some of the recent achievements towards the design and discovery of apicoplast targeted antimalarial compounds. PMID- 27381079 TI - Plant chimeras: The good, the bad, and the 'Bizzaria'. AB - Chimeras - organisms that are composed of cells of more than one genotype - captured the human imagination long before they were formally described and used in the laboratory. These organisms owe their namesake to a fire-breathing monster from Greek mythology that has the head of a lion, the body of a goat, and the tail of a serpent. The first description of a non-fictional chimera dates back to the middle of the seventeenth century when the Florentine gardener Pietro Nati discovered an adventitious shoot growing from the graft junction between sour orange (Citrus aurantium) and citron (Citrus medica). This perplexing chimera that grows with sectors phenotypically resembling each of the citrus progenitors inspired discussion and wonder from the scientific community and was fittingly named the 'Bizzaria'. Initially, the 'Bizzaria' was believed to be an asexual hybrid that formed from a cellular fusion between the grafted parents; however, in-depth cellular analyses carried out centuries later demonstrated that the 'Bizzaria', along with other chimeras, owe their unique sectored appearance to a conglomeration of cells from the two donors. Since this pivotal discovery at the turn of the twentieth century, chimeras have served both as tools and as unique biological phenomena that have contributed to our understanding of plant development at the cellular, tissue, and organismal level. Rapid advancements in genome sequencing technologies have enabled the establishment of new model species with novel morphological and developmental features that enable the generation of chimeric organisms. In this review, we show that genetic mosaic and chimera studies provide a technologically simple way to delve into the organismal, genetic, and genomic inner workings underlying the development of diverse model organisms. Moreover, we discuss the unique opportunity that chimeras present to explore universal principles governing intercellular communication and the coordination of organismal biology in a heterogenomic landscape. PMID- 27381081 TI - Spatial non-uniformity in exfoliated WS2 single layers. AB - Monolayers of transition metal dichalcogenides (TMDs) are atomically thin two dimensional crystals with attractive optoelectronic properties, which are promising for emerging applications in nanophotonics. Here, we report on the extraordinary spatial non-uniformity of the photoluminescence (PL) and strain properties of exfoliated WS2 monolayers. Specifically, it is shown that the edges of such monolayers exhibit remarkably enhanced PL intensity compared to their respective central area. A comprehensive analysis of the recombination channels involved in the PL process demonstrates a spatial non-uniformity across the monolayer's surface and reflects on the non-uniformity of the intrinsic electron density across the monolayer. Auger electron imaging and spectroscopy studies complemented with PL measurements in different environments indicate that oxygen chemisorption and physisorption are the two fundamental mechanisms responsible for the observed non-uniformity. At the same time Raman spectroscopy analysis shows remarkable strain variations among the different locations of an individual monolayer, however such variations cannot be strictly correlated with the non uniform PL emission. Our results shed light on the role of the chemical bonding in the competition between exciton complexes in monolayer WS2, providing a method of engineering new nanophotonic functions using WS2 monolayers. It is therefore envisaged that our findings could find diverse applications towards the development of TMD-based optoelectronic devices. PMID- 27381080 TI - Dipeptidyl Peptidase-4 Inhibitor Increases Vascular Leakage in Retina through VE cadherin Phosphorylation. AB - The inhibitors of CD26 (dipeptidyl peptidase-4; DPP4) have been widely prescribed to control glucose level in diabetic patients. DPP4-inhibitors, however, accumulate stromal cell-derived factor-1alpha (SDF-1alpha), a well-known inducer of vascular leakage and angiogenesis both of which are fundamental pathophysiology of diabetic retinopathy. The aim of this study was to investigate the effects of DPP4-inhibitors on vascular permeability and diabetic retinopathy. DPP4-inhibitor (diprotin A or sitagliptin) increased the phosphorylation of Src and vascular endothelial-cadherin (VE-cadherin) in human endothelial cells and disrupted endothelial cell-to-cell junctions, which were attenuated by CXCR4 (receptor of SDF-1alpha)-blocker or Src-inhibitor. Disruption of endothelial cell to-cell junctions in the immuno-fluorescence images correlated with the actual leakage of the endothelial monolayer in the transwell endothelial permeability assay. In the Miles assay, vascular leakage was observed in the ears into which SDF-1alpha was injected, and this effect was aggravated by DPP4-inhibitor. In the model of retinopathy of prematurity, DPP4-inhibitor increased not only retinal vascularity but also leakage. Additionally, in the murine diabetic retinopathy model, DPP4-inhibitor increased the phosphorylation of Src and VE-cadherin and aggravated vascular leakage in the retinas. Collectively, DPP4-inhibitor induced vascular leakage by augmenting the SDF-1alpha/CXCR4/Src/VE-cadherin signaling pathway. These data highlight safety issues associated with the use of DPP4 inhibitors. PMID- 27381082 TI - Polyphenolic compounds with anti-tumour potential from Corchorus olitorius (L.) Tiliaceae, a Nigerian leaf vegetable. AB - Chromatographic fractionation of the methanolic extract of Corchorus olitorius (L.) (Tiliaceae), on silica gel yielded two polyphenolic compounds. The structures of the compounds were elucidated as Methyl-1,4,5-tri-O-caffeoyl quinate and trans-3-(4-Hydroxy-3-methoxyphenyl)acrylic anhydride, based on extensive use of spectroscopic techniques such as (1)H and (13)C NMR, DEPT and 2D NMR experiments (COSY, HSQC, HMBC), IR and MS. To establish an initial proof-of concept for the biological relevance of these compounds, their cytotoxicity against the cancer cell lines HeLa, HL460 and PC3, which might indicate their anti-tumour potential, was assessed. The compounds when tested at a range of concentrations up to 1.6mM were found to possess mild cytotoxic activity which was significant against HeLa cells at ?800MUM. The trans-3-(4-Hydroxy-3-methoxyl phenyl)acrylic anhydride was found to be related to curcumin, a compound known to have anti-cancer activity. Docking of each of the two compounds and also of curcumin into some molecular targets implicated in tumourigenesis revealed that the three compounds had binding affinities that were superior to those obtained for the co-crystallized inhibitors of metalloproteinase-9, fibroblast growth factor receptor 2 (FGFR2) and epidermal growth factor receptor (EGFR). The plant Corchorus olitorius therefore represents a potential source of natural 'lead' compounds with anti-tumour potential. PMID- 27381084 TI - Synthesis of MR-49, a deiodinated analog of tetraiodothyroacetic acid (tetrac), as a novel pro-angiogenesis modulator. AB - The tyrosine-based hormones 3,3',5-triiodo-l-thyronine (l-T3) and l-thyroxine (l T4) that are produced by the thyroid gland control metabolic functions. Iodothyronine deiodinase enzymes convert l-T4 to l-T3, the form of thyroid hormone critical to genomic actions within cells and regulation of metabolism, and to reverse-l-T3, a hormone isoform that is largely inactive. We used tertiary amines in a study of deiodination based on derivatives of tetraiodothyroacetic acid (tetrac)-a naturally occurring derivative of l-T4-to mimic the action of the iodothyronine deiodinases and deiodination of the outer ring iodines. Deiodinated tetrac, MR-49, was found to be pro-angiogenic, with this activity exceeding that of l-T3 and l-T4 in a hemoglobin Matrigel(r) plug assay of angiogenesis. Tetrac is anti-angiogenic via several nongenomic pathways, and the present studies of MR 49 reveal the critical contribution of outer ring iodines to the angiogenic properties of thyroid hormone analogues, which may have utility as pro-angiogenic pharmaceuticals. PMID- 27381085 TI - Corrigendum to "Assessing the oral bioavailability of difluorosialic acid prodrugs, potent viral neuraminidase inhibitors, using a snapshot PK screening assay" [Bioorg. Med. Chem. Lett. 25 (2015) 2505-2509]. PMID- 27381083 TI - Optimization of pyrazole-containing 1,2,4-triazolo-[3,4-b]thiadiazines, a new class of STAT3 pathway inhibitors. AB - Structure-activity relationship studies of a 1,2,4-triazolo-[3,4-b]thiadiazine scaffold, identified in an HTS campaign for selective STAT3 pathway inhibitors, determined that a pyrazole group and specific aryl substitution on the thiadiazine were necessary for activity. Improvements in potency and metabolic stability were accomplished by the introduction of an alpha-methyl group on the thiadiazine. Optimized compounds exhibited anti-proliferative activity, reduction of phosphorylated STAT3 levels and effects on STAT3 target genes. These compounds represent a starting point for further drug discovery efforts targeting the STAT3 pathway. PMID- 27381086 TI - Selective 5-HT2C receptor agonists: Design and synthesis of pyridazine-fused azepines. AB - Heterocycle-fused azepines are discussed as potent 5-HT2C receptor agonists with excellent selectivity over 5-HT2B agonism. Synthesis and structure activity relationships are outlined for a series of bicyclic pyridazino[3,4-d]azepines. By comparison with earlier published work, in vitro assays predict a high probability for achieving CNS penetration for a potent and selective compound 15a, a pre-requisite to achieve in vivo efficacy. PMID- 27381087 TI - Changes in the plasma proteome at asymptomatic and symptomatic stages of autosomal dominant Alzheimer's disease. AB - The autosomal dominant form of Alzheimer's disease (ADAD) is far less prevalent than late onset Alzheimer's disease (LOAD), but enables well-informed prospective studies, since symptom onset is near certain and age of onset is predictable. Our aim was to discover plasma proteins associated with early AD pathology by investigating plasma protein changes at the asymptomatic and symptomatic stages of ADAD. Eighty-one proteins were compared across asymptomatic mutation carriers (aMC, n = 15), symptomatic mutation carriers (sMC, n = 8) and related noncarriers (NC, n = 12). Proteins were also tested for associations with cognitive measures, brain amyloid deposition and glucose metabolism. Fewer changes were observed at the asymptomatic than symptomatic stage with seven and 16 proteins altered significantly in aMC and sMC, respectively. This included complement components C3, C5, C6, apolipoproteins A-I, A-IV, C-I and M, histidine-rich glycoprotein, heparin cofactor II and attractin, which are involved in inflammation, lipid metabolism and vascular health. Proteins involved in lipid metabolism differed only at the symptomatic stage, whereas changes in inflammation and vascular health were evident at asymptomatic and symptomatic stages. Due to increasing evidence supporting the usefulness of ADAD as a model for LOAD, these proteins warrant further investigation into their potential association with early stages of LOAD. PMID- 27381088 TI - Effect of nicotine on cariogenic virulence of Streptococcus mutans. AB - Nicotine has well-documented effects on the growth and colonization of Streptococcus mutans. This study attempts to investigate the effects of nicotine on pathogenic factors of S. mutans, such as the effect on biofilm formation and viability, expression of pathogenic genes, and metabolites of S. mutans. The results demonstrated that addition of nicotine did not significantly influence the viability of S. mutans cells. The biofilms became increasingly compact as the concentrations of nicotine increased. The expression of virulence genes, such as ldh and phosphotransferase system (PTS)-associated genes, was upregulated, and nlmC was upregulated significantly, while ftf was downregulated. The lactate concentration of S. mutans grown in 1 mg/mL of nicotine was increased up to twofold over either biofilm or planktonic cells grown without nicotine. Changes in the metabolites involved in central carbon metabolism from sucrose indicated that most selected metabolites were detectable and influenced by increased concentrations of nicotine. This study demonstrated that nicotine can influence the pathogenicity of S. mutans and may lead to increased dental caries through the production of more lactate and the upregulation of virulence genes. PMID- 27381089 TI - Abnormal functional connectivity and cortical integrity influence dominant hand motor disability in multiple sclerosis: a multimodal analysis. AB - Functional reorganization and structural damage occur in the brains of people with multiple sclerosis (MS) throughout the disease course. However, the relationship between resting-state functional connectivity (FC) reorganization in the sensorimotor network and motor disability in MS is not well understood. This study used resting-state fMRI, T1-weighted and T2-weighted, and magnetization transfer (MT) imaging to investigate the relationship between abnormal FC in the sensorimotor network and upper limb motor disability in people with MS, as well as the impact of disease-related structural abnormalities within this network. Specifically, the differences in FC of the left hemisphere hand motor region between MS participants with preserved (n = 17) and impaired (n = 26) right hand function, compared with healthy controls (n = 20) was investigated. Differences in brain atrophy and MT ratio measured at the global and regional levels were also investigated between the three groups. Motor preserved MS participants had stronger FC in structurally intact visual information processing regions relative to motor impaired MS participants. Motor impaired MS participants showed weaker FC in the sensorimotor and somatosensory association cortices and more severe structural damage throughout the brain compared with the other groups. Logistic regression analysis showed that regional MTR predicted motor disability beyond the impact of global atrophy whereas regional grey matter volume did not. More importantly, as the first multimodal analysis combining resting-state fMRI, T1 weighted, T2-weighted and MTR images in MS, we demonstrate how a combination of structural and functional changes may contribute to motor impairment or preservation in MS. Hum Brain Mapp 37:4262-4275, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27381091 TI - Challenges raised by cross-border testing of rare diseases in the European union. AB - As the availability of genetic tests has grown rapidly during the last decade along with the increasing knowledge of the genetic background of rare inherited diseases, sending DNA samples to another country for analysis has become more of a routine than an exception in clinical diagnostics. Nonetheless, few studies of cross-border genetic testing of rare diseases in the European Union (EU) have been carried out, and data about the challenges and problems related to cross border testing are lacking. The purpose of this study was to investigate the experiences of the molecular genetic laboratories and the clinical genetics units concerning the cross-border genetic testing of rare diseases in the Member States of the EU. Data were collected using web-based questionnaires and phone interviews targeted at laboratories and clinical units registered with the Orphanet database. The specific aims were to clarify the volume, quality and challenges of cross-border genetic testing. The results revealed, for example, that the variability of the required documentation creates confusion and, unexpectedly, sample dispatch was considered a major problem in cross-border testing. In addition, the differences between countries regarding the reimbursement and authorization policies of cross-border testing were significant, thus confirming the pre-existing assumption about unequal access to genetic testing in the different Member States. To facilitate and organize cross border testing, common practices need to be created at the level of the EU, and follow-up studies are needed to monitor their effects. PMID- 27381090 TI - MSX1 mutations and associated disease phenotypes: genotype-phenotype relations. AB - The Msx1 transcription factor is involved in multiple epithelial-mesenchymal interactions during vertebrate embryogenesis. It has pleiotropic effects in several tissues. In humans, MSX1 variants have been related to tooth agenesis, orofacial clefting, and nail dysplasia. We correlate all MSX1 disease causing variants to phenotypic features to shed light on this hitherto unclear association. MSX1 truncations cause more severe phenotypes than in-frame variants. Mutations in the homeodomain always cause tooth agenesis with or without other phenotypes while mutations outside the homeodomain are mostly associated with non-syndromic orofacial clefts. Downstream effects can be further explored by the edgetic perturbation model. This information provides new insights for genetic diagnosis and for further functional analysis of MSX1 variants. PMID- 27381092 TI - Estrogen-related receptor gamma implicated in a phenotype including hearing loss and mild developmental delay. AB - Analysis of chromosomal rearrangements has been highly successful in identifying genes involved in many congenital abnormalities including hearing loss. Herein, we report a subject, designated DGAP242, with congenital hearing loss (HL) and a de novo balanced translocation 46,XX,t(1;5)(q32;q15)dn. Using multiple next generation sequencing techniques, we obtained high resolution of the breakpoints. This revealed disruption of the orphan receptor ESRRG on chromosome 1, which is differentially expressed in inner ear hair cells and has previously been implicated in HL, and disruption of KIAA0825 on chromosome 5. Given the translocation breakpoints and supporting literature, disruption of ESRRG is the most likely cause for DGAP242's phenotype and implicates ESRRG in a monogenic form of congenital HL, although a putative contributory role for KIAA0825 in the subject's disorder cannot be excluded. PMID- 27381093 TI - Protein-altering MYH3 variants are associated with a spectrum of phenotypes extending to spondylocarpotarsal synostosis syndrome. AB - Spondylocarpotarsal synostosis syndrome (SCT) is a rare Mendelian disorder (OMIM #272460) characterized by prenatal vertebral fusion, scoliosis, short stature and carpal and tarsal synostosis. SCT is typically known as an autosomal recessive disease caused by variants in the FLNB gene. The genetic basis of the rarer cases of vertical transmissions remains unknown. In two independent families with symptoms related to autosomal dominant SCT, we identified - by exome sequencing - two protein-altering variants in the embryonic myosin heavy chain 3 (MYH3) gene. As MYH3 variants are also associated with distal arthrogryposis (DA1, DA2A, DA2B) and autosomal dominant multiple pterygium syndromes (MPS), the present study expands the phenotypic spectrum of MYH3 variants to autosomal dominant SCT. Vertebral, carpal and tarsal fusions observed in both families further confirm that MYH3 plays a key role in skeletal development. PMID- 27381094 TI - Clinical utility gene card for: Aniridia. PMID- 27381096 TI - Different hollow and spherical TiO2 morphologies have distinct activities for the photocatalytic inactivation of chemical and biological agents. AB - The inactivation of Escherichia coli and Qbeta phage was examined following their photocatalytic treatment with TiO2 hollows and spheres that had been prepared by electrospray, hydrothermal treatment, and calcination. The crystal structures of the hollows and spheres were assigned to TiO2 anatase, and the surface areas of the hollows and spheres were determined to be 91 and 79 m(2) g(-1), respectively. Interestingly, TiO2 spheres exhibited higher anti-pathogen performance than TiO2 hollows, a difference we ascribe to the prevention of light multi-scattering by microorganisms covering the surfaces of the TiO2 particles. The photocatalytic decomposition of dimethyl sulfoxide (DMSO) in the presence of TiO2 hollows and spheres was examined in order to study the dependence of photocatalytic activity on TiO2 morphology for the size scale of the reactants. TiO2 hollows provided greater photocatalytic decomposition of DMSO than did TiO2 spheres, in contrast to the pattern seen for pathogen inactivation. Fabrication of photocatalysts will need to vary depending on what substance (e.g., organic compound or biological agent) is being targeted for environmental remediation. PMID- 27381098 TI - Training neurologists in India: Past, present and future. PMID- 27381095 TI - The mRNA-bound proteome of the human malaria parasite Plasmodium falciparum. AB - BACKGROUND: Gene expression is controlled at multiple levels, including transcription, stability, translation, and degradation. Over the years, it has become apparent that Plasmodium falciparum exerts limited transcriptional control of gene expression, while at least part of Plasmodium's genome is controlled by post-transcriptional mechanisms. To generate insights into the mechanisms that regulate gene expression at the post-transcriptional level, we undertook complementary computational, comparative genomics, and experimental approaches to identify and characterize mRNA-binding proteins (mRBPs) in P. falciparum. RESULTS: Close to 1000 RNA-binding proteins are identified by hidden Markov model searches, of which mRBPs encompass a relatively large proportion of the parasite proteome as compared to other eukaryotes. Several abundant mRNA-binding domains are enriched in apicomplexan parasites, while strong depletion of mRNA-binding domains involved in RNA degradation is observed. Next, we experimentally capture 199 proteins that interact with mRNA during the blood stages, 64 of which with high confidence. These captured mRBPs show a significant overlap with the in silico identified candidate RBPs (p < 0.0001). Among the experimentally validated mRBPs are many known translational regulators active in other stages of the parasite's life cycle, such as DOZI, CITH, PfCELF2, Musashi, and PfAlba1-4. Finally, we also detect several proteins with an RNA-binding domain abundant in Apicomplexans (RAP domain) that is almost exclusively found in apicomplexan parasites. CONCLUSIONS: Collectively, our results provide the most complete comparative genomics and experimental analysis of mRBPs in P. falciparum. A better understanding of these regulatory proteins will not only give insight into the intricate parasite life cycle but may also provide targets for novel therapeutic strategies. PMID- 27381099 TI - Stuck to the ventilator: The neuromyopathy of critical illness. PMID- 27381100 TI - Weakness in the critically ill: Can we predict and prevent? PMID- 27381101 TI - The war against shunt infections - fighting with our backs to the wall! PMID- 27381102 TI - The guilty microbes in shunt infection: Is there an emerging trend? PMID- 27381103 TI - Cell therapy for neurological disorders: The elusive goal. AB - The positive outcomes of the transplantation of fetal neural tissue in adult rat models of a variety of neurological disorders, particularly Parkinson's disease, in the 1970s, and its translation to humans in the 1980s, raised great hopes for patients suffering from these incurable disorders. This resulted in a frantic research globally to find more suitable, reliable, and ethically acceptable alternatives. The discovery of adult stem cells, embryonic stem cells, and more recently, the induced pluripotent cells further raised our expectations. The useful functional recovery in animal models using these cell transplantation techniques coupled with the desperate needs of such patients prompted many surgeons to "jump from the rat-to-man" without scientifically establishing a proof of their utility. Each new development claimed to overcome the limitations, shortcomings, safety, and other technical problems associated with the earlier technique, yet newer difficulties prevented evidence-based acceptance of their clinical use. However, thousands of patients across the globe have received these therapies without a scientifically acceptable proof of their reliability. The present review is an attempt to summarize the current status of cell therapy for neurological disorders. PMID- 27381104 TI - Radiosurgery for the management of refractory trigeminal neuralgia. AB - Gamma Knife stereotactic radiosurgery (SRS) is a minimally invasive surgical approach for managing medically refractory trigeminal neuralgia (TN). The goal of trigeminal neuralgia SRS is to eliminate or reduce the facial pain in order to improve the quality of life. Over the past 28 years, 1250 patients have undergone gamma knife SRS for TN at our institution. In our retrospective review of 503 patients who underwent SRS for management of refractory TN, 449 patients (89%) experienced initial pain relief at a median latency of 1 month. At the one year mark, 73% patients were pain free (with or without medications) and 80% had pain control. Repeat radiosurgery was performed for 193 patients (43%). At the one year mark, 26% of these patients were completely pain free and 78% were pain free with or without medications. The role of gamma Knife SRS in the management of medically refractory trigeminal neuralgia has evolved over the past two decades. SRS is a minimally invasive procedure and is associated with 60-90% rate of pain relief in patents with medical refractory trigeminal neuralgia. Early intervention with SRS as the initial surgical procedure for management of refractory trigeminal neuralgia is associated with faster, better, and longer pain relief. As SRS is the least invasive procedure for TN, it is a good treatment option for patients with other high-risk medical conditions. SRS is an attractive alternative especially to those who do not want to accept the greater risk associated with other surgical procedures. PMID- 27381105 TI - NFU1 gene mutation and mitochondrial disorders. AB - Mitochondrial respiratory chains consist of approximately 100 structural proteins. Thirteen of these structural proteins are encoded by mitochondrial DNA (mtDNA), and the others by nuclear DNA (nDNA). Mutation in any of the mitochondrial structural-protein related genes, regardless of whether they are in the nDNA or mtDNA, might cause mitochondrial disorders. In the recent past, new nuclear genes required for assembly, maintenance, and translation of respiratory chain proteins have been found. Mutation in these genes might also cause mitochondrial disorders (MD). NFU1 gene is one of such genes and has a role in the assembly of iron-sulfur cluster (ISC). ISCs are included in a variety of metalloproteins, such as the ferredoxins, as well as in enzymatic reactions and have been first identified in the oxidation-reduction reactions of mitochondrial electron transport. It is important to be aware of NFU1 gene mutations that may cause severe mitochondrial respiratory chain defects, mitochondrial encephalomyopathies and death, early in life. PMID- 27381106 TI - Correlation between qualitative balance indices, dynamic posturography and structural brain imaging in patients with progressive supranuclear palsy and its subtypes. AB - OBJECTIVES: To compare the clinical, balance, and radiological profile of progressive supranuclear palsy (PSP) of Richardson type (PSP-R) and Parkinsonian type (PSP-P). MATERIALS AND METHODS: Twenty-nine patients with PSP (PSP-R: 17, PSP-P: 12) satisfying the probable/possible National Institute of Neurological Disorders and Stroke-PSP criteria were recruited and assessed with Unified Parkinson's Disease Rating Scale-III, PSP rating scale (PSPRS), Berg balance scale (BBS), Tinetti performance-oriented mobility assessment gait and total (TPG and TPT) score, dynamic posturography (DP), and magnetic resonance imaging. Data were compared with 30 age- and gender-matched healthy controls. RESULTS: The mean ages of PSP-R, PSP-P, and controls were comparable (62.5 +/- 6.6, 59 +/- 8.9, and 59.8 +/- 7.6 years). The PSP group had significantly poor DP scores and more radiological abnormalities than controls. The PSPRS, TPG, and TPT scores were significantly more impaired in PSP-R compared to PSP-P (P = 0.045, P = 0.031, and P = 0.037, respectively). In DP, the limits of overall stability were most significant (P < 0.001) and PSP-R had lower scores. PSP-R compared to PSP-P had more often "Humming Bird" sign (P < 0.001), "Morning Glory" sign (P < 0.008), and generalized cortical atrophy (P < 0.001). The area of midbrain (P < 0.002) and midbrain/pons ratio (P < 0.013) was significantly lower in PSP-R. In PSP-P, the overall balance index significantly correlated with BBS, TPG, and TPT (r = -0.79, P = 0.002; r = -0.772, P = 0.003; and r = -0.688, P = 0.013) and the midbrain axial anterior-posterior diameter significantly correlated with the TPG and TPT (r = 0.74, P = 0.01; r = 0.66, P = 0.018). CONCLUSIONS: While balance and radiological abnormalities were more severe in PSP-R, the qualitative and quantitative measurements of severity of balance in PSP-P rather than PSP-R was a better reflection of the pathology of the midbrain. PMID- 27381107 TI - Acute Physiology and Chronic Health Evaluation II score of >=15: A risk factor for sepsis-induced critical illness polyneuropathy. AB - BACKGROUND: Critical illness polyneuropathy (CIP) is a common complication of severe sepsis and systemic inflammatory response syndrome (SIRS). The risk factors for sepsis-induced CIP have not been well established. AIM: The aim of this study was to find out the risk factors of sepsis-induced CIP, especially its relationship with the severity of illness. PATIENTS AND METHODS: A cohort of 100 patients with sepsis defined as SIRS of proven or presumed microbial etiology were followed up with nerve conduction studies (NCS) performed within the first 14 days of admission. If the assessment was normal then the study was repeated between day 21 and 28. The two groups (with and without neuropathy) were compared. The following risk factors were evaluated for the development of sepsis related CIP: Duration of symptoms, stay in Intensive Care Unit, and mechanical ventilation; use of neuromuscular blocking agents (NMBAs), steroids, insulin infusion, and inotropes. The following laboratory parameters recorded in the first 24 h of admission were included: Hemoglobin (Hb), total leukocyte count, serum urea, creatinine, aminotransaminases (aspartate aminotransferase and alanine aminotransferase), total protein, albumin, potassium, creatinine kinase, plasma glucose, HbA1C, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score at admission or within 24 h. RESULTS: Thirty-seven patients had features of neuropathy. Among these 37 patients, 30 patients (81%) developed it in the first 14 days. Multivariate analysis using linear regression showed the APACHE II score and use of NMBAs to be significant factors in its development. An APACHE II score of >=15 was associated with a significant risk of developing CIP (relative risk: 11.6, 95% confidence interval: 4.9-27.2, P < 0.0001). CONCLUSION: Critically ill patients with sepsis and APACHE II score at admission or within 24 h of >=15 are at risk for the development of CIP. PMID- 27381108 TI - Early neurological and cognitive impairments in subclinical cerebrovascular disease. AB - BACKGROUND: The subclinical cerebrovascular disease (SCVD) is an important public health problem with demonstrated prognostic significance for stroke, future cognitive decline, and progression to dementia. The earliest possible detection of the silent presence of SCVD in adults at age at risk with normal functioning is very important for both clinical doctors and scientists. MATERIALS AND METHODS: Seventy-seven adult volunteers, recruited during the years 2005-2007, with mean age 58.7 (standard deviation 5.9) years, were assessed by four subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB)-Eclipse cognitive assessment system. We used a questionnaire survey for the presence of cerebrovascular risk factors (CVRFs) such as arterial hypertension, smoking and dyslipidemia, among others, as well as instrumental (Doppler examination) and neurological magnetic resonance imaging (MRI) procedures. Descriptive statistics, comparison (t-test, Chi-square) and univariate methods were used as followed by multifactor logistic regression and receiver operating characteristics analyses. RESULTS: The risk factor questionnaire revealed nonspecific symptoms in 44 (67.7%) of the subjects. In 42 (64.6%) of all 65 subjects, we found at least one of the conventional CVRFs. Abnormal findings from the extra- and trans-cranial Doppler examination were established in 38 (58.5%) of all studied volunteers. Thirty-four subjects had brain MRI (52.3%), and abnormal findings were found in 12 (35.3%) of them. Two of the four subtests of CANTAB tool appeared to be potentially promising predictors of the outcome, as found at the univariate analysis (spatial working memory 1 [SWM1] total errors; intra-extra dimensional set 1 [IED1] total errors [adjusted]; IED2 total trials [adjusted]). We established that the best accuracy of 82.5% was achieved by a multifactor interaction logistic regression model, with the role CVRF and combined CANTAB predictor "IED total ratio (errors/trials) * SWM1 total errors" (P = 0.006). CONCLUSIONS: Our results have contributed to the hypothesis that it is possible to identify, by noninvasive methods, subjects at age at risk who have mild degree of cognitive impairment and to establish the significant relationship of this impairment with existing CVRFs, nonspecific symptoms and subclinical abnormal brain Doppler/MRI findings. We created a combined neuropsychological predictor that was able to clearly distinguish between the presence and absence of abnormal Doppler/MRI findings. This pilot prognostic model showed a relatively high accuracy of >80%; therefore, the predictors may serve as biomarkers for SCVD in subjects at age at risk (51-65 years). PMID- 27381109 TI - Cognitive function and activities of daily living in people affected by leprosy: A cross-sectional, population-based, case-control study. AB - OBJECTIVES: There has been controversy regarding whether or not people affected by leprosy have more cognitive dysfunction than healthy individuals. The purpose of this study was to assess cognitive functions and activities of daily living (ADL) in people affected by leprosy relative to a control population living in rural areas. MATERIALS AND METHODS: We assessed cognitive functions and ADL using the Korean Mini-Mental State Examination (K-MMSE), Korean Dementia Screening Questionnaire (KDSQ), and Seoul-Instrumental ADL (S-IADL). Higher scores of K MMSE and lower scores of both KDSQ and S-IADL are indicative of better functioning. We assessed 224 persons living in Sorokdo who were affected by leprosy and 448 age- and gender-matched control subjects living in Namwon of the Chonbuk province. RESULTS: After adjusting for age, gender, and educational status, the K-MMSE score was found to be significantly higher in people affected by leprosy than in control subjects (23.14 +/- 4.89 vs. 22.25 +/- 4.62, respectively, P = 0.022). Items related to memory in the KDSQ showed no differences between the groups, but people affected by leprosy had a better score in division for other cognitive functions than controls. On items related to ADL in the KDSQ and S-IADL, people affected by leprosy performed significantly worse compared with controls. CONCLUSIONS: Our results suggest that although people affected by leprosy have a lower capacity of ADL, they may have better cognitive functions than normal controls. PMID- 27381110 TI - Leprosy and cognition. PMID- 27381111 TI - Differential expression levels of collagen 1A2, tissue inhibitor of metalloproteinase 4, and cathepsin B in intracranial aneurysms. AB - AIMS: Intracranial aneurysms (IAs) express a variety of differentially expressed genes when compared to the normal artery. The aim of this study was to evaluate the expression level of a few genes in the aneurysm wall and to correlate them with various clinicoradiological factors. MATERIALS AND METHODS: The mRNA level of collagen 1A2 (COL1A2), tissue inhibitor of metalloproteinase 4 (TIMP4), and cathepsin B (CTSB) genes were studied in 23 aneurysmal walls and 19 superficial temporal arteries harvested from 23 patients undergoing clipping of IAs, by real time polymerase chain reaction method. RESULTS: The mean fold change of COL1A2 gene between the aneurysm sample and the superficial temporal artery (STA) sample was 2.46 +/- 0.12, that of TIMP4 gene was 0.31 +/- 0, and that of CTSB gene was 31.47 +/- 39.01. There was a positive correlation of TIMP4 expression level with maximum diameter of aneurysm (P = 0.008) and fundus of aneurysm (P = 0.012). The mean fold change of CTSB of patients who had preoperative hydrocephalus in the computed tomogram (CT) scan of the head at admission was 56.16 and that of the patients who did not have hydrocephalus was 13.51 (P = 0.008). The mean fold change of CTSB of patients who developed fresh postoperative deficits or worsening of the preexisting deficits was 23.64 and that of the patients who did not develop was 42.22 (P = 0.039). CONCLUSIONS: COL1A2 gene and CTSB genes were overexpressed, and TIMP4 gene was underexpressed in the aneurysmal sac compared to STA and their expression levels were associated with a few clinicoradiological factors. PMID- 27381112 TI - Ventriculoperitoneal shunt tube infection and changing pattern of antibiotic sensitivity in neurosurgery practice: Alarming trends. AB - INTRODUCTION: Infection associated with a ventriculoperitoneal shunt is a severe complication with a high morbidity and substantial mortality. There are no guidelines to choose antibiotics in case of shunt infection. Most surgeons use antibiotics of their choice whereas limited centres follow their own antibiotic policy. An alarming increase in antibiotic resistance has led to rising morbidity and mortality. MATERIALS AND METHODS: This was a retrospective analysis of patients who underwent ventriculoperitoneal shunt surgery between January 2010 and December 2015 at our institution. Shunt tubes and cerebrospinal fluid were sent for culture and sensitivity in patients who were suspected clinically of having shunt tube infections. The processing of the samples was done by standard techniques, and the identification of the organism along with its sensitivity pattern was performed using Vitek 2 system. RESULTS: A total of 1186 ventriculoperitoneal shunt surgeries were performed during this period at our institute in patients of all age groups. There were 757 (63.8%) male and 429 (36.2%) female patients. A total of 156 samples of patients were sent for culture and sensitivity during this period, out of which 79 (50.6%) samples had growth of an organism either in the cerebrospinal fluid [36 (23.1%)], shunt tubing [16 (10.2%)], or in both [27 (17.3%)]. The most common organisms grown in the cultures were Staphylococcus aureus [65 (82.3%)] or coagulase-negative Staphylococcus [22 (25.3%)] in the Gram-positive group and Escherichia coli [17 (21.5%)] in the Gram-negative group. Over the last 6 years, the sensitivity pattern of both Gram-negative and Gram-positive bacteria has shown alarming decreasing sensitivity for various commonly used antibiotics. CONCLUSION: Ventriculoperitoneal shunt infection has become an important concern in cases of hydrocephalus. Due to the development of a high proportion of antibiotic resistance, we recommend an empirical therapy of antibiotic therapy for prophylaxis and suspected infection in ventriculoperitoneal shunt surgery. PMID- 27381114 TI - Lumbar canal stenosis: Clinical, radiological and functional outcome. PMID- 27381113 TI - Clinical, radiological, and functional evaluation of surgical treatment in degenerative lumbar canal stenosis. AB - BACKGROUND: Lumbar spinal stenosis is a frequent indication for spinal surgery. The clinical symptoms may not be accurately reflected on radiological studies. Treatment is aimed at not only obtaining immediate pain relief but also in preventing its long-term disabling sequelae. The walking ability needs to be correlated with functional outcome measures in assessing patients with symptomatic lumbar canal stenosis (LCS). AIMS AND OBJECTIVES: To study and evaluate the outcome of surgery for degenerative LCS on a clinical, radiological, and functional basis, and to establish an association between various factors that may be influencing the development of LCS. MATERIALS AND METHODS: A prospective study of 48 patients was carried out at the Department of Neurosurgery, Sri Venkateswara Institute of Medical Sciences, Tirupathi, in whom the LCS was confirmed and measured on magnetic resonance imaging images by thecal sac cross-sectional area (CSA). Their functional assessment was done by motorized treadmill test for assessment of the time of appearance of first symptom and the maximum walking distance. The visual analog scale (VAS), Oswestry disability index (ODI), Japanese Orthopedic Association (JOA) score, and Short Form-36 (SF 36) score were also evaluated. CONCLUSIONS: The post-operative VAS, ODI, JOA, SF 36 scores showed a significant improvement from the preoperative ones. Postoperative thecal sac measurements showed a significant neural decompression substantiating the results of improvement in the functional assessment scores after surgery. The treadmill test is a quantifiable means of dynamic function. It may be considered as a useful tool for the assessment of functional impairment and for the correlation of thecal sac CSA with lumbar canal stenosis. A combination of functional scores, treadmill test, and thecal sac CSA may be included in the preoperative assessment of outcome in patients with LCS. PMID- 27381115 TI - Risk factors responsible for the volume of hemorrhage in aneurysmal subarachnoid hemorrhage. AB - BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a medical emergency with a high mortality and morbidity. There is a marked association of the ensuing neurological functional deficits following aSAH with the volume of hemorrhage. The volume of intracranial hemorrhage in aSAH is usually quantified by the revised Fisher grades. MATERIALS AND METHODS: A total of 155 patients who suffered from aSAH were evaluated for risk factors that led to an increased volume of intracranial hemorrhage. These included various demographic factors, the medical history, the preadmission blood pressure, and the aneurysm characteristics. RESULTS: The number of aneurysms was significantly related to poor revised Fisher grades (grade 3 or 4; P = 0.016). Thus, the presence of multiple aneurysms (2-4) was a significant risk factor responsible for a poor modified Fisher grade (odds ratio [OR] = 4.0, P = 0.004). Significantly higher risk of intracranial hemorrhage was also observed for aneurysms located on the the internal carotid artery (ICA), anterior communicating artery (ACOA), or middle cerebral artery (MCA) when compared with other sites (P < 0.001). Bleeding in ACOA was significantly associated with a poor Fisher's grade (OR = 4.3, P = 0.025). Additionally, the preadmission diastolic blood pressure (DBP) alone was significantly associated with a poor Fisher grade (P = 0.024). CONCLUSION: Preadmission DBP, multiple aneurysms, and aneurysms of the ACOA are associated with markedly increased volume of hemorrhage as evaluated by the revised Fisher grades. Thus, patients harboring an intracranial aneurysm having the above mentioned features should seek an early intervention in order to prevent the occurrence of aSAH. PMID- 27381116 TI - "Vices of my blood" - Risk factors of subarachnoid hemorrhage. PMID- 27381117 TI - Endovascular treatment of A1 aneurysms of the anterior cerebral artery. AB - AIM: The aim of this study was to present the clinical and angiographic outcomes of A1 aneurysms treated by coil embolization. MATERIALS AND METHODS: We retrospectively evaluated 38 consecutive patients with A1 aneurysm (20 ruptured and 18 unruptured; mean age, 53.8 +/- 11.9 years) from 2011 to 2014 treated by an endovascular approach in our hospital. Follow-up angiography was obtained in 30 patients. Clinical outcomes were evaluated by modified Rankin Scale (mRS) over telephone. RESULTS: Among the 38 patients, 24 were treated with single-catheter technique, 8 with stent-assisted coiling (Enterprise 3; Solitaire 5), 5 with parent vessel obliteration, and 1 with balloon-assisted coiling. Initial angiographic results revealed that complete occlusion was achieved in 21 aneurysms (55.3%), near-complete occlusion in 16 (42.1%), and partial occlusion with contrast agent filling the aneurysm sac in 1 (2.6%). Procedure-related complications were observed in 6 patients (15.8%). Follow-up angiographic imaging evaluation after coil embolization was performed in 32 aneurysms (mean interval, 22.6 +/- 6.7 months), which showed that 31 (96.9%) aneurysms remained stable or improved without regrowth, while minor recanalization was found in 1 aneurysm (3.1%), which was treated by parent vessel occlusion. Clinical follow-up evaluation was excellent in 37 of the 38 patients (mRS score 0 in 34, and mRS score 1 in 3) at a mean duration of 26.6 +/- 7.7 months. CONCLUSIONS: Endovascular treatment is feasible and effective for A1 segment aneurysms. The current treatment selections, including single-catheter embolization, balloon assisted coiling, stent-assisted coiling, and parent vessel occlusion, should be performed according to the characteristics and morphology of A1 aneurysms. PMID- 27381118 TI - Endovascular treatment of A1 segment aneurysms. PMID- 27381119 TI - Highest cited papers published in Neurology India: An analysis for the years 1993 2014. AB - CONTEXT: The highest cited papers published in a journal provide a snapshot of the clinical practice and research in that specialty and/or region. AIMS: The aim of this study was to determine the highest cited papers published in Neurology India and analyze their attributes. SETTING AND DESIGN: This study was a citation analysis of all papers published in Neurology India since online archiving commenced in 1993. METHODS: All papers published in Neurology India between the years 1993-2014 were listed. The number of times each paper had been cited up till the time of performing this study was determined by performing a Google Scholar search. Published papers were then ranked on the basis of total times cited since publication and the annual citation rate. Statistical Techniques: Simple counts and percentages were used to report most results. The mean citations received by papers in various categories were compared using the Student's t-test or a one-way analysis of variance, as appropriate. All analyses were carried out on SAS University Edition (SAS/STAT(r), SAS Institute Inc, NC, USA) and graphs were generated on MS Excel 2016. RESULTS: The top papers on the total citations and annual citation rate rank lists pertained to basic neuroscience research. The highest cited paper overall had received 139 citations. About a quarter of the papers published had never been cited at all. The major themes represented were vascular diseases and infections. CONCLUSIONS: The highest cited papers reflect the diseases that are of major concern in India. Certain domains such as trauma, allied neurosciences, and basic neuroscience research were underrepresented. PMID- 27381120 TI - Scientific publications and emerging Indian neuroscientists. PMID- 27381121 TI - Endoscopic pituitary surgery: Techniques, tips and tricks, nuances, and complication avoidance. AB - Endoscopic pituitary surgery is useful in all micro- and macro-pituitary adenomas including those with suprasellar and cavernous sinus extension. The endoscope provides a panoramic close-up, a multi-angled view with excellent illumination and magnification, permitting complete excision of the tumor with preservation of normal pituitary. However, surgeons need to learn altogether different skills unique to endoscopy and the learning curve is steep. The learning curve can be shortened by proper selection of cases, gradual transition from the microscopic to the endoscopic approach, adequate sphenoethmoidal recess widening, identification of important landmarks during each stage of surgery, and use of neuronavigation. Results and long term outcomes can be improved with bimanual dynamic dissection and sequential tumor excision, preservation of normal pituitary, avoidance of arachnoidal tear and use of extended approach for tumors with large suprasellar extension. The gradual transition from microscopic to endoscopic approach, adherence to step by step technique and learning 'tips and tricks' of the endoscopic pituitary surgery reduce complications. PMID- 27381122 TI - Glioblastoma multiforme masquerading as a tumefactive demyelinating lesion: Lessons learned at autopsy. AB - Tumefactive demyelinating (TD) lesions are extremely challenging lesions to diagnose during their histopathological examination and are often misdiagnosed as tumors. On the contrary, a glioblastoma multiforme is rarely misdiagnosed as a TD unless the two coexist. We present a case of a 60-year old man who was diagnosed as having tumefactive demyelination on a stereotactic biopsy. At autopsy, however, the lesion revealed a grade IV glioblastoma. The myelin loss along the periphery of the lesion was erroneously interpreted as TD during the histopathological examination. We have described the imaging, the biopsy, and the autopsy findings of this instructive case. It is pertinent to recognize its histology to prevent a misdiagnosis. PMID- 27381123 TI - Consent taking in neurosurgery: Education and tips for safe practice. AB - Neurosurgery is the most difficult branch of surgery and interventions may occasionally lead to a poor prognosis. Most of the times, one would assume that the likely outcome of a surgery is going to be good; however, not so uncommonly, the results may be devastating. Poor outcomes are further compounded by litigations, which are rising. The safety for neurosurgeon is the consent signed by the patient that ensures some defense. There are no guidelines given by the society and the controlling authorities on what constitutes a real consent. Some judgments by Supreme Court have given us some lead; however, a large part of the complexities involved in the consent process remain unresolved. We, therefore, have to frame our own guidelines and standards that shall be uniformly adapted by all of us. We can even set a precedent for other disciplines of surgery to follow regarding consent-taking for neurosurgery. This shall also serve as a foundation for the wider benefit and safety of surgeons from other disciplines. This paper is an attempt to simplify the complexities of the consent taking process and aims to provide adequate education and information about the nuances of informed consent. PMID- 27381124 TI - History and evolution of neurosurgery in Assam. AB - Assam is a land of rich traditions and culture and advanced medical facilities that are comparable with facilities throughout the world. In this article, the history of development of Neurosciences in Assam is traced. PMID- 27381126 TI - "Pink pinna sign": A harbinger of lamotrigene-induced serious drug rash. PMID- 27381127 TI - Myasthenia gravis accompanied by Graves' disease, thyrotoxic hypokalemic periodic paralysis and thymic hyperplasia. PMID- 27381128 TI - Statin-associated ocular myopathy mimicking ocular myasthenia: Rare occurrence. PMID- 27381129 TI - A case of subcortical heterotopia presenting with focal motor seizures and sensory loss. PMID- 27381130 TI - Brain MRI findings in a patient with scrub typhus infection. PMID- 27381131 TI - Paroxysmal kinesigenic dyskinesia: A frequently misdiagnosed movement disorder. PMID- 27381133 TI - Fresh frozen plasma for plasma exchange - How safe is it? PMID- 27381132 TI - Phenytoin-induced rhabdomyolysis: Timely recognition for safely remission. PMID- 27381134 TI - ADAPT for emergent stroke treatment: Newer technique, Indian experience. PMID- 27381135 TI - Recurrent myelopathy and optic neuritis associated with systemic lupus erythematosus. PMID- 27381136 TI - A forgotten cause of bilateral wrist drop. PMID- 27381137 TI - Clear cell sarcoma of the paraspinal ligament - A rare tumor at an unusual location: A review. PMID- 27381138 TI - Pathologically proven peripheral neurolymphomatosis. PMID- 27381139 TI - Permanent spinal cord injury during lumbar spinal anesthesia: A report of two cases. PMID- 27381140 TI - Traumatic bilateral atlantoaxial rotatory subluxation with hangman fracture in an adult. PMID- 27381141 TI - Wooden spinal model for teaching and training. PMID- 27381142 TI - Spontaneous non-thrombotic regression of vein of Galen malformation in a child following shunt surgery. PMID- 27381143 TI - Migration of a lateral ventricular choroid plexus papilloma: An uncommon occurrence. PMID- 27381144 TI - Turban-like transcalvarial destructive mass in a young child, with extensive extracranial and intracerebral involvement: A cytological diagnosis and review. PMID- 27381145 TI - Cavernous malformation in the conus medullaris: A rare report. PMID- 27381147 TI - Integrated PET/MRI imaging of semantic dementia. PMID- 27381146 TI - Giant arteriovenous malformation in the conus medullaris mimicking a tumor. PMID- 27381148 TI - Churg-Strauss syndrome in a pediatric patient presenting with recurrent hemorrhagic stroke and mitral regurgitation due to a prolapsed mitral valve. PMID- 27381149 TI - Prenatal Blake pouch cyst with hydrocephalus. PMID- 27381150 TI - Idiopathic ventral herniation of the spinal cord. PMID- 27381151 TI - Postmyelitis pygalgia. PMID- 27381152 TI - Third ventricular craniopharyngioma. PMID- 27381153 TI - Bilateral cranio-orbital neurofibromas in a 16-year-old child with neurofibromatosis 1. PMID- 27381155 TI - Author's reply. PMID- 27381154 TI - Is instability the nodal point of pathogenesis for both cervical spondylotic myelopathy and ossified posterior longitudinal ligament? PMID- 27381156 TI - Interpreting forest plots and funnel plots in meta-analysis. PMID- 27381157 TI - Achalasia and amyotrophic lateral sclerosis as part of Allgrove syndrome. PMID- 27381158 TI - Authors' reply. PMID- 27381159 TI - Calcified worm in the brain. PMID- 27381160 TI - Authors' reply. PMID- 27381165 TI - Can hydroxyurea serve as a free radical scavenger and reduce iron overload in beta-thalassemia patients? AB - In this study, we hypothesize that hydroxyurea could provide an additional benefit as a free radical scavenger and/or iron chelator in beta-thalassemia patients with iron overload. Twenty-one beta-thalassemia intermedia patients who presented between 3 and 17 years but later required regular blood transfusions were enrolled for hydroxyurea therapy for a year. Fourteen patients responded to the therapy with hemoglobin levels maintained above 7.5 g/dl without transfusions. Hydroxyurea was discontinued after 6 months in seven patients who did not respond to the therapy and had to be continued on regular blood transfusions. We observed a statistically significant decrease in serum ferritin levels from 4194 +/- 4850 ng/ml to 2129 +/- 2380 ng/ml among the responders and from 2955 +/- 2909 ng/ml to 2040 +/- 2432 ng/ml among the non-responders and statistically significant decrease in labile iron pool from 18678.7 +/- 10067.4 mean fluorescence intensity (MFI) to 14888.5 +/- 5284.0 MFI among responders and from 17986.3 +/- 9079.8 MFI to 15634.8 +/- 8976.9 MFI among the non-responders after therapy. Phosphatidylserine externalization also showed a statistically significant decrease from 44.2 +/- 22.2 MFI to 16.6 +/- 6.7 MFI among the responders and from 46.9 +/- 33.1 MFI to 39.8 +/- 7.4 MFI among the non responders along with a statistically significant decrease in the levels of reactive oxygen species from 72.8 +/- 35.5 MFI to 29.0 +/- 8.3 MFI among the responders and from 80.9 +/- 41.4 MFI to 40.5 +/- 15.8 MFI among the non responders after therapy. A statistically significant increase in reduced glutathione levels was also observed from 430.8 +/- 201.1 MFI to 715.5 +/- 292.4 MFI among the responders and from 359.6 +/- 165.6 MFI to 450.3 +/- 279.5 MFI among the non-responders after therapy. This suggests the possible additional role of hydroxyurea as a free radical scavenger and/or iron chelator but requires a larger study for substantiation. PMID- 27381163 TI - Signal transduction controls heterogeneous NF-kappaB dynamics and target gene expression through cytokine-specific refractory states. AB - Cells respond dynamically to pulsatile cytokine stimulation. Here we report that single, or well-spaced pulses of TNFalpha (>100 min apart) give a high probability of NF-kappaB activation. However, fewer cells respond to shorter pulse intervals (<100 min) suggesting a heterogeneous refractory state. This refractory state is established in the signal transduction network downstream of TNFR and upstream of IKK, and depends on the level of the NF-kappaB system negative feedback protein A20. If a second pulse within the refractory phase is IL-1beta instead of TNFalpha, all of the cells respond. This suggests a mechanism by which two cytokines can synergistically activate an inflammatory response. Gene expression analyses show strong correlation between the cellular dynamic response and NF-kappaB-dependent target gene activation. These data suggest that refractory states in the NF-kappaB system constitute an inherent design motif of the inflammatory response and we suggest that this may avoid harmful homogenous cellular activation. PMID- 27381164 TI - Role of astrocyte-synapse interactions in CNS disorders. AB - Astrocytes comprise half of the cells in the brain. Although astrocytes have traditionally been described as playing a supportive role for neurons, they have recently been recognized as active participants in the development and plasticity of dendritic spines and synapses. Astrocytes can eliminate dendritic spines, induce synapse formation, and regulate neurotransmission and plasticity. Dendritic spine and synapse impairments are features of many neurological disorders, including autism spectrum disorder, schizophrenia, and Alzheimer's disease. In this review we will present evidence from multiple neurological disorders demonstrating that changes in astrocyte-synapse interaction contribute to the pathologies. Genomic analysis has connected altered astrocytic gene expression with synaptic deficits in a number of neurological disorders. Alterations in astrocyte-secreted factors have been implicated in the neuronal morphology and synaptic changes seen in neurodevelopmental disorders, while alteration in astrocytic glutamate uptake is a core feature of multiple neurodegenerative disorders. This evidence clearly demonstrates that maintaining astrocyte-synapse interaction is crucial for normal central nervous system functioning. Obtaining a better understanding of the role of astrocytes at synapses in health and disease will provide a new avenue for future therapeutic targeting. PMID- 27381166 TI - Effect of hepatitis B virus infection on sperm quality and oxidative stress state of the semen of infertile males. AB - PROBLEM: The effects of hepatitis B virus (HBV) infection on sperm quality and oxidative stress state of the semen of infertile males remain undetermined. METHOD OF STUDY: Normal males and 60 semen samples from infertile males (with or without HBV infection) were subjected to semen analysis. RESULTS: Semen volume, semen pH, sperm density, percentage of forward, movement of sperm, sperm activation rate, sperm survival rate, rate of normal sperm morphology of infertile males with HBV infection were significantly lower than those of infertile males without genital infection and of normal males (P<.05), while interleukin (IL)-17, IL-18, and malondialdehyde (MDA) levels in subjects with HBV infection were significantly higher than those of infertile males without genital infection and of normal males (P<.05). In patients with HBV infection, MDA level was found to be negatively correlated with semen quality, but positively correlated with semen IL-17 and IL-18 concentrations. CONCLUSIONS: HBV infection increased MDA level, induced abnormal expression of IL-17 and IL-18, and negatively affected male reproductive capacity, resulting in male infertility. PMID- 27381167 TI - Radiographic, Surgeon and Owner Assessment of the BioMedtrix TATE((r)) Elbow Arthroplasty. AB - OBJECTIVE: To report the long-term radiographic and clinical outcome of the BioMedtrix TATE elbow arthroplasty system in dogs. Assessment was via radiographs, a surgeon-based questionnaire, and owner assessment of outcome using the Liverpool osteoarthritis in dogs (LOAD) and canine brief pain inventory (CBPI) questionnaires. STUDY DESIGN: Retrospective multicenter, case series. ANIMALS: Client-owned dogs undergoing TATE elbow arthroplasty. METHODS: Questionnaires were distributed to surgeons in the United Kingdom performing TATE elbow arthroplasty and to the owners of the dogs operated on. Owners completed the LOAD and CBPI questionnaires. All completed questionnaires from surgeons and owners, and radiographs of the dogs were collated and analyzed. RESULTS: Surgeon questionnaires and radiographs were obtained for 33 elbows from 32 dogs, with owner questionnaires obtained for 19 dogs. Perioperative, short-term, and mid term complication rates were 60%, 15%, and 15%, respectively. Radiographic assessment of component alignment showed 62% of cartridges were valgus or varus malaligned and 56% of cartridges were either translated medially or laterally relative to the long axis of the ulnar. There was no significant association between component alignment and final clinical outcome. Surgeon assessment reported 24% of dogs to have full, 52% acceptable, and 24% unacceptable outcome. Owner assessment showed significant decreases in pain severity and pain interference from preoperative to final status but no change in mobility scores. CONCLUSIONS: A high complication rate and variability in component placement was recorded with TATE athroplasty. However, component malalignment did not negatively impact clinical outcome. Final clinical outcome was favorable for most cases with significant reductions in pain severity and interference scores despite no changes in mobility scores. PMID- 27381168 TI - Effect of maternal supplementation with fish oil during pregnancy and lactation on allergy development in childhood. PMID- 27381170 TI - Dressing up posture: The interactive effects of posture and clothing on competency judgements. AB - Individuals often receive judgements from others based on their clothing and their posture. While both of these factors have been found to influence judgements of competency independently, their relative importance in impression formation is yet to be investigated. We address this by examining interactive effects of posture and clothing on four competency measures: confidence, professionalism, approachability, and likeliness of a high salary. Participants rated photographs of both male and female models pictured in different postures (strong, neutral, weak) in smart clothing (a suit for males; both a trouser suit and skirt suit for females) and casual clothing. We confirm that posture manipulations affected judgements of individuals differently according to the clothing they were pictured in. The nature of these interactions varied by gender and, for women, competency judgements differed according to attire type (trouser or skirt suit). The implications of these findings in relation to impression formation are discussed. PMID- 27381169 TI - Why Do Lithium-Oxygen Batteries Fail: Parasitic Chemical Reactions and Their Synergistic Effect. AB - As an electrochemical energy-storage technology with the highest theoretical capacity, lithium-oxygen batteries face critical challenges in terms of poor stabilities and low charge/discharge round-trip efficiencies. It is generally recognized that these issues are connected to the parasitic chemical reactions at the anode, electrolyte, and cathode. While the detailed mechanisms of these reactions have been studied separately, the possible synergistic effects between these reactions remain poorly understood. To fill in the knowledge gap, this Minireview examines literature reports on the parasitic chemical reactions and finds the reactive oxygen species a key chemical mediator that participates in or facilitates nearly all parasitic chemical reactions. Given the ubiquitous presence of oxygen in all test cells, this finding is important. It offers new insights into how to stabilize various components of lithium-oxygen batteries for high-performance operations and how to eventually materialize the full potentials of this promising technology. PMID- 27381171 TI - Epidural analgesia combined with a comprehensive physiotherapy program after Cytoreductive Surgery and HIPEC is associated with enhanced post-operative recovery and reduces intensive care unit stay: A retrospective study of 124 patients. AB - BACKGROUND: Although Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) confers health benefits in peritoneal carcinomatosis (PC) treatment, it is associated with significant postoperative morbidity and mortality rate with increased length of hospital stay. The goal of this study is to determine whether a new comprehensive physiotherapy program including epidural loco-regional analgesia can improve the quality of care and patients recovery. METHODS: Between 2009 and 2013, 124 patients with PC were operated for CRS and HIPEC procedures. These patients were analyzed and divided in 2 groups by means of time. No Physio group included patients operated from 2009 to 2011 (n = 57) having a thoracic patient controlled epidural analgesia (PCEA) but no preoperative physiotherapy program. The Physio group included patients operated from 2012 to 2013 (n = 67) having both a PCEA with a preoperative physiotherapy program. RESULTS: The mortality rate was 1.6% (n = 2). The median length of stay in the intensive care unit (ICU) was lower in the Physio group, 2 days vs. 0 for No Physio group (p < 0.0001). The first time of mobilization after surgery was shorter in the Physio group (day 3 vs. 2, p = 0.0043). The overall satisfaction in the Physio group was achieved in 93% of patients, helping in decreasing fear of surgery and mobilization in 70% and 84% of cases respectively. CONCLUSION: Our study demonstrates that a clear pre-operative information and education by a physiotherapist, associated with a PCEA-pain management significantly benefits the patient's post-operative recovery and reduces the length of stay in the ICU. PMID- 27381172 TI - Computational Prediction of Electron Ionization Mass Spectra to Assist in GC/MS Compound Identification. AB - We describe a tool, competitive fragmentation modeling for electron ionization (CFM-EI) that, given a chemical structure (e.g., in SMILES or InChI format), computationally predicts an electron ionization mass spectrum (EI-MS) (i.e., the type of mass spectrum commonly generated by gas chromatography mass spectrometry). The predicted spectra produced by this tool can be used for putative compound identification, complementing measured spectra in reference databases by expanding the range of compounds able to be considered when availability of measured spectra is limited. The tool extends CFM-ESI, a recently developed method for computational prediction of electrospray tandem mass spectra (ESI-MS/MS), but unlike CFM-ESI, CFM-EI can handle odd-electron ions and isotopes and incorporates an artificial neural network. Tests on EI-MS data from the NIST database demonstrate that CFM-EI is able to model fragmentation likelihoods in low-resolution EI-MS data, producing predicted spectra whose dot product scores are significantly better than full enumeration "bar-code" spectra. CFM-EI also outperformed previously reported results for MetFrag, MOLGEN-MS, and Mass Frontier on one compound identification task. It also outperformed MetFrag in a range of other compound identification tasks involving a much larger data set, containing both derivatized and nonderivatized compounds. While replicate EI-MS measurements of chemical standards are still a more accurate point of comparison, CFM-EI's predictions provide a much-needed alternative when no reference standard is available for measurement. CFM-EI is available at https://sourceforge.net/projects/cfm-id/ for download and http://cfmid.wishartlab.com as a web service. PMID- 27381173 TI - SLC6A4 promoter region methylation and socio-emotional stress response in very preterm and full-term infants. AB - AIM: The present study is part of a prospective micro-longitudinal research project and reports on the association between SLC6A4 methylation and socio emotional stress response in very preterm (VPT) and full-term (FT) infants. MATERIALS & METHODS: SLC6A4 methylation was assessed at birth and discharge in 32 VPT infants, and at birth in 27 FT infants. Socio-emotional stress response (i.e., negative emotionality) was assessed at 3 months (corrected age). RESULTS: Negative emotionality was higher in VPTs compared with FT counterpart. In VPT infants only, stress response was associated with SLC6A4 methylation status at discharge, which was predictive of greater negative emotionality. CONCLUSION: The present study extends previous reports, suggesting that altered SLC6A4 methylation associates with greater socio-emotional stress sensitivity in 3-month old VPT infants. PMID- 27381175 TI - New insight into the dynamical system of alphaB-crystallin oligomers. AB - alpha-Crystallin possesses a dynamic quaternary structure mediated by its subunit dynamics. Elucidation of a mechanism of subunit dynamics in homo-oligomers of alphaB-crystallin was tackled through deuteration-assisted small-angle neutron scattering (DA-SANS) and electrospray ionization (ESI) native mass spectrometry (nMS). The existence of subunit exchange was confirmed with DA-SANS, and monomers liberated from the oligomers were observed with nMS. With increasing temperature, an increase in both the exchange rate and monomer population was observed despite the absence of oligomer collapse. It is proposed that transiently liberated subunits, namely, "traveling subunits," play a role in subunit exchange. Moreover, we propose that protein function is regulated by these traveling subunits. PMID- 27381174 TI - GerM is required to assemble the basal platform of the SpoIIIA-SpoIIQ transenvelope complex during sporulation in Bacillus subtilis. AB - Sporulating Bacillus subtilis cells assemble a multimeric membrane complex connecting the mother cell and developing spore that is required to maintain forespore differentiation. An early step in the assembly of this transenvelope complex (called the A-Q complex) is an interaction between the extracellular domains of the forespore membrane protein SpoIIQ and the mother cell membrane protein SpoIIIAH. This interaction provides a platform onto which the remaining components of the complex assemble and also functions as an anchor for cell-cell signalling and morphogenetic proteins involved in spore development. SpoIIQ is required to recruit SpoIIIAH to the sporulation septum on the mother cell side; however, the mechanism by which SpoIIQ specifically localizes to the septal membranes on the forespore side has remained enigmatic. Here, we identify GerM, a lipoprotein previously implicated in spore germination, as the missing factor required for SpoIIQ localization. Our data indicate that GerM and SpoIIIAH, derived from the mother cell, and SpoIIQ, from the forespore, have reciprocal localization dependencies suggesting they constitute a tripartite platform for the assembly of the A-Q complex and a hub for the localization of mother cell and forespore proteins. PMID- 27381176 TI - Further evidence that a variant of the gene NUDT15 may be an important predictor of azathioprine-induced toxicity in Chinese subjects: a case report. AB - WHAT IS KNOWN AND OBJECTIVE: Thiopurine methyltransferase (TPMT) enzyme is an important component in the metabolism of azathioprine (AZA). Its mutation may lead to AZA-induced toxicity. The dysfunctional genetic variant TPMT *3C is of low frequency among Asians. Moreover, AZA-induced toxicity still occurs in some patients with normal TPMT activity. This suggests that additional factors, including other genetic variants, may contribute to such toxicity. Recent studies described a strong association between a variant of the NUDT15, a gene that mediates the hydrolysis of some nucleoside diphosphate derivatives, and thiopurine-related myelosuppression in Asians. We report the first case of a Chinese patient with AZA-induced severe toxicity with no clinically significant TPMT variant but with the NUDT15 c.415C>T allele. CASE SUMMARY: A 40-year-old Chinese patient with PBC-AIH overlap syndrome had been receiving for one month, azathioprine (50 mg/day) and methylprednisolone (24 mg/day) based on his TPMT*3C wild-type genotype. The patient developed serious myelosuppression and hair loss. AZA was stopped, and the patient was given liver-protective drugs and supportive treatment. TPMT and NUDT15 gene sequencing suggests that NUDT15 c.415C>T mutation was the likely cause of the adverse reaction. WHAT IS NEW AND CONCLUSION: NUDT15 c.415C>T may be another predictor of AZA-induced leukocytopenia. If further well controlled studies validate this association with sufficient predictive power, NUDT15 and TPMT genotyping before starting AZA treatment may become appropriate. PMID- 27381178 TI - Pontibacillus salipaludis sp. nov., a slightly halophilic bacterium isolated from a salt pan. AB - Two novel Gram-stain-positive, facultatively anerobic, rod-shaped, motile, endospore-forming bacterial strains, 9DMT and 6DM, were isolated from Tuticorn, India. The high 16S rRNA gene sequence similarity (99.9 %) and DNA-DNA relatedness (88+/-2 %) indicated that strains 9DMT and 6DM were members of a single species. Based on 16S rRNA gene sequence analysis these strains were identified as belonging to the genus Pontibacillus and were related most closely to the type strains of Pontibacillus chungwhensis (99.7 % sequence similarity) and Pontibacillus marinus (97.9 %). The DNA G+C content of strains 9DMT and 6DM was 41.6 and 41.4 mol%, respectively. However, the level of DNA-DNA relatedness of these strains with P. chungwhensis KCTC 3890T and P. marinus KCTC 3917T was only 40.9 + 0.8 and 39.8 + 0.9 %, respectively. Strains 9DMT and 6DM were facultative anaerobes with optimal growth at 37 degrees C, at pH 7.0-8.0 and with 2-3 % (w/v) NaCl. The cell-wall peptidoglycan of strain 9DMT contained meso diaminopimelic acid. Polar lipids included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, a phospholipid and three unknown lipids. The isoprenoid quinone was MK-7. Major fatty acids of strain 9DMT were anteiso-C15 : 0, iso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0. The results of phylogenetic, chemotaxonomic and biochemical tests allowed the clear differentiation of strains 9DMT and 6DM, which are considered to represent a novel member of the genus Pontibacillus, for which the name Pontibacillus salipaludis sp. nov. is proposed. The type strain is 9DMT (= KCTC 33742T=LMG 29102T= CGMCC 1.15353T). PMID- 27381177 TI - Dirty and 40 days in the wilderness: Eliciting childbirth and postnatal cultural practices and beliefs in Nepal. AB - BACKGROUND: Pregnancy and childbirth are socio-cultural events that carry varying meanings across different societies and cultures. These are often translated into social expectations of what a particular society expects women to do (or not to do) during pregnancy, birth and/or the postnatal period. This paper reports a study exploring beliefs around childbirth in Nepal, a low-income country with a largely Hindu population. The paper then sets these findings in the context of the wider global literature around issues such as periods where women are viewed as polluted (or dirty even) after childbirth. METHODS: A qualitative study comprising five in-depth face-to-face interviews and 14 focus group discussions with mainly women, but also men and health service providers. The qualitative findings in Nepal were compared and contrasted with the literature on practices and cultural beliefs related to the pregnancy and childbirth period across the globe and at different times in history. RESULTS: The themes that emerged from the analysis included: (a) cord cutting & placenta rituals; (b) rest & seclusion; (c) purification, naming & weaning ceremonies and (d) nutrition and breastfeeding. Physiological changes in mother and baby may underpin the various beliefs, ritual and practices in the postnatal period. These practices often mean women do not access postnatal health services. CONCLUSIONS: The cultural practices, taboos and beliefs during pregnancy and around childbirth found in Nepal largely resonate with those reported across the globe. This paper stresses that local people's beliefs and practices offer both opportunities and barriers to health service providers. Maternity care providers need to be aware of local values, beliefs and traditions to anticipate and meet the needs of women, gain their trust and work with them. PMID- 27381179 TI - Minimally Invasive and Open Distal Chevron Osteotomy for Mild to Moderate Hallux Valgus. AB - BACKGROUND: Minimally invasive surgical (MIS) techniques are increasingly being used in foot and ankle surgery but it is important that they are adopted only once they have been shown to be equivalent or superior to open techniques. We believe that the main advantages of MIS are found in the early postoperative period, but in order to adopt it as a technique longer-term studies are required. The aim of this study was to compare the 2-year outcomes of a third-generation MIS distal chevron osteotomy with a comparable traditional open distal chevron osteotomy for mild-moderate hallux valgus. Our null hypothesis was that the 2 techniques would yield equivalent clinical and radiographic results at 2 years. METHODS: This was a retrospective cohort study. Eighty-one consecutive feet (49 MIS and 32 open distal chevron osteotomies) were followed up for a minimum 24 months (range 24-58). All patients were clinically assessed using the Manchester Oxford Foot Questionnaire. Radiographic measures included hallux valgus angle, the intermetatarsal angle, hallux interphalangeal angle, metatarsal phalangeal joint angle, distal metatarsal articular angle, tibial sesamoid position, shape of the first metatarsal head, and plantar offset. Statistical analysis was done using Student t test or Wilcoxon rank-sum test for continuous data and Pearson chi-square test for categorical data. RESULTS: Clinical and radiologic postoperative scores in all domains were substantially improved in both groups (P < .001), but there was no statistically significant difference in improvement of any domain between open and MIS groups (P > .05). There were no significant differences in complications between the 2 groups ( > .5). CONCLUSION: The midterm results of this third-generation technique show that it was a safe procedure with good clinical outcomes and comparable to traditional open techniques for symptomatic mild-moderate hallux valgus. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 27381180 TI - Husband/Partner Intoxication and Intimate Partner Violence Against Women in the Philippines. AB - This study examined husband/partner intoxication and experience with physical, sexual, and emotional intimate partner violence against women (IPVAW) using data derived from a nationally representative survey conducted in the Philippines in 2013. Multivariate logistic regression analyses were used to examine the association between intoxication and 3 different types of intimate partner violence against women. Multinomial logistic regression was used to examine intoxication and severity of violence. In this sample, 28.8% of women reported experiencing any form of intimate partner violence and 92.9% of women reported their partner being intoxicated at least sometimes. Intoxication was significantly associated with all 3 types of intimate partner violence, while the odds of experiencing one form of IPVAW versus no form of IPVAW and 2 forms of IPVAW versus 1 form of IPVAW was greater among women reporting frequency of husband/partner intoxication as often. PMID- 27381181 TI - Evidence for the Role of BAG3 in Mitochondrial Quality Control in Cardiomyocytes. AB - Mitochondrial abnormalities impact the development of myofibrillar myopathies. Therefore, understanding the mechanisms underlying the removal of dysfunctional mitochondria from cells is of great importance toward understanding the molecular events involved in the genesis of cardiomyopathy. Earlier studies have ascribed a role for BAG3 in the development of cardiomyopathy in experimental animals leading to the identification of BAG3 mutations in patients with heart failure which may play a part in the onset of disease development and progression. BAG3 is co-chaperone of heat shock protein 70 (HSP70), which has been shown to modulate apoptosis and autophagy, in several cell models. In this study, we explore the potential role of BAG3 in mitochondrial quality control. We demonstrate that siRNA mediated suppression of BAG3 production in neonatal rat ventricular cardiomyocytes (NRVCs) significantly elevates the level of Parkin, a key component of mitophagy. We found that both BAG3 and Parkin are recruited to depolarized mitochondria and promote mitophagy. Suppression of BAG3 in NRVCs significantly reduces autophagy flux and eliminates clearance of Tom20, an essential import receptor for mitochondria proteins, after induction of mitophagy. These observations suggest that BAG3 is critical for the maintenance of mitochondrial homeostasis under stress conditions, and disruptions in BAG3 expression impact cardiomyocyte function. J. Cell. Physiol. 232: 797-805, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27381182 TI - A crystal-clear zebrafish for in vivo imaging. AB - The larval zebrafish (Danio rerio) is an excellent vertebrate model for in vivo imaging of biological phenomena at subcellular, cellular and systems levels. However, the optical accessibility of highly pigmented tissues, like the eyes, is limited even in this animal model. Typical strategies to improve the transparency of zebrafish larvae require the use of either highly toxic chemical compounds (e.g. 1-phenyl-2-thiourea, PTU) or pigmentation mutant strains (e.g. casper mutant). To date none of these strategies produce normally behaving larvae that are transparent in both the body and the eyes. Here we present crystal, an optically clear zebrafish mutant obtained by combining different viable mutations affecting skin pigmentation. Compared to the previously described combinatorial mutant casper, the crystal mutant lacks pigmentation also in the retinal pigment epithelium, therefore enabling optical access to the eyes. Unlike PTU-treated animals, crystal larvae are able to perform visually guided behaviours, such as the optomotor response, as efficiently as wild type larvae. To validate the in vivo application of crystal larvae, we performed whole-brain light-sheet imaging and two-photon calcium imaging of neural activity in the retina. In conclusion, this novel combinatorial pigmentation mutant represents an ideal vertebrate tool for completely unobstructed structural and functional in vivo investigations of biological processes, particularly when imaging tissues inside or between the eyes. PMID- 27381183 TI - How vision and self-motion combine or compete during path reproduction changes with age. AB - Human adults can optimally integrate visual and non-visual self-motion cues when navigating, while children up to 8 years old cannot. Whether older children can is unknown, limiting our understanding of how our internal multisensory representation of space develops. Eighteen adults and fifteen 10- to 11-year-old children were guided along a two-legged path in darkness (self-motion only), in a virtual room (visual + self-motion), or were shown a pre-recorded walk in the virtual room while standing still (visual only). Participants then reproduced the path in darkness. We obtained a measure of the dispersion of the end-points (variable error) and of their distances from the correct end point (constant error). Only children reduced their variable error when recalling the path in the visual + self-motion condition, indicating combination of these cues. Adults showed a constant error for the combined condition intermediate to those for single cues, indicative of cue competition, which may explain the lack of near optimal integration in this group. This suggests that later in childhood humans can gain from optimally integrating spatial cues even when in the same situation these are kept separate in adulthood. PMID- 27381186 TI - Correction: Number density distribution of solvent molecules on a substrate: a transform theory for atomic force microscopy. AB - Correction for 'Number density distribution of solvent molecules on a substrate: a transform theory for atomic force microscopy' by Ken-ichi Amano et al., Phys. Chem. Chem. Phys., 2016, 18, 15534-15544. PMID- 27381184 TI - A porcine model of relief of unilateral ureteral obstruction: study on self repairing capability over multiple time points. AB - It is still controversial whether renal tubular interstitial fibrosis (TIF) is a reversible process. Although previous studies examining TIF have been carried out in rodents, their kidney size and physiological character differ with humans, and the difference among diverse individuals before and after damage was obvious. Thus an experimental animal model to simulate human kidney disease was urged to be established. In order to clarify whether TIF is reversible, and the exact time points that the kidney has the capacity to be repaired, a porcine relief of unilateral ureteral obstruction (R-UUO) model was developed. Kidney damage and reparation were observed dynamically in vivo over various time points. Pigs were randomized divided into three groups (n = 6): UUO 5 days group, UUO 7 days, and UUO 10 days group. Each porcine in that groups underwent UUO and subsequent R-UUO for three time points. Renal function, histological structure, and protein expressions of alpha-smooth muscle actin (alpha-SMA), vimentin and E-cadherin were evaluated at different time points. Following R-UUO after 5 and 7 days of UUO, compared to UUO, serum creatinine levels were significantly decreased. Renal pathological tissue damage was repaired. The expressions of alpha-SMA and vimentin were decreased and E-cadherin expression was increased (P < 0.05). However, during R-UUO 14, 28, and 56 days after 10 days of UUO, serum creatinine was not decreased significantly. The expressions of alpha-SMA and vimentin consistently remained at high levels. Renal damage was unable to be restored and resulted in chronic lesions. Kidney damage induced by UUO can be reversed in early stages. However, longer time of UUO with significant levels of TIF showed limited reversibility. The porcine R-UUO model provides an ideal animal model for the investigation of kidney injury and repair as well as for the evaluation of the effect of drug treatment. PMID- 27381185 TI - Assessment and treatment of eating disorders in children and adolescents. AB - Feeding and eating disorders (FEDs) are serious mental health disorders that cause impairments in physical health, development, cognition and psychosocial function and can go undetected for months or years. They are characterised by disturbed eating behaviour associated with concerns about weight and shape or by disinterest in food, phobic avoidance or avoidance due to sensory aspects of food. Restrictive forms of FEDs lead to significant weight loss requiring intervention. Without specific knowledge of these conditions, they can evade detection, delaying time to diagnosis and treatment and potentially influencing outcome. This review article focuses on the key factors involved in the psychiatric assessment and treatment of four feeding or eating disorders (EDs): anorexia nervosa, avoidant-restrictive food intake disorder, bulimia nervosa and binge eating disorder. They have been chosen for discussion as they are most likely to be encountered in both a psychiatric and paediatric setting. It emphasises the importance of a family-focused, developmentally appropriate and multidisciplinary approach to care. It does not address aspects of medical assessment and treatment. Other feeding or EDs not included in this article are pica, rumination disorder, other specified feeding and eating disorder and unspecified feeding and eating disorder. PMID- 27381187 TI - Developing Street-Level PM2.5 and PM10 Land Use Regression Models in High-Density Hong Kong with Urban Morphological Factors. AB - Monitoring street-level particulates is essential to air quality management but challenging in high-density Hong Kong due to limitations in local monitoring network and the complexities of street environment. By employing vehicle-based mobile measurements, land use regression (LUR) models were developed to estimate the spatial variation of PM2.5 and PM10 in the downtown area of Hong Kong. Sampling runs were conducted along routes measuring a total of 30 km during a selected measurement period of total 14 days. In total, 321 independent variables were examined to develop LUR models by using stepwise regression with PM2.5 and PM10 as dependent variables. Approximately, 10% increases in the model adjusted R(2) were achieved by integrating urban/building morphology as independent variables into the LUR models. Resultant LUR models show that the most decisive factors on street-level air quality in Hong Kong are frontal area index, an urban/building morphological parameter, and road network line density and traffic volume, two parameters of road traffic. The adjusted R(2) of the final LUR models of PM2.5 and PM10 are 0.633 and 0.707, respectively. These results indicate that urban morphology is more decisive to the street-level air quality in high-density cities than other cities. Air pollution hotspots were also identified based on the LUR mapping. PMID- 27381188 TI - Peptides from sesame cake extend healthspan of Caenorhabditis elegans via upregulation of skn-1 and inhibition of intracellular ROS levels. AB - The peptides from sesame cake (PSC) which are the main by-product of agricultural processing of sesame were prepared. To evaluate benefits of PSC for health and longevity, antioxidant activity and anti-aging effects were studied in vitro and in a Caenorhabditis elegans (C. elegans) model system. PSC exhibited antioxidant activity in vitro, and induced beneficial effects on lifespan and several health parameters of C.elegans, including pharyngeal pumping rate, locomotion and lipofuscin accumulation. In a mev-1 mutant, PSC increased lifespan, and it enhanced oxidative stress tolerance in wild-type nematodes. After treatment with PSC, SOD activity, GSH content, and GSH/GSSG ratio were increased, leading to low intracellular ROS levels in C. elegans. PSC up-regulated skn-1 mRNA, and its target gene gcs-1, and abolished the extension of lifespan in skn-1 mutant, indicating that PSC-mediated longevity is dependent on activation of the skn 1/Nrf-2 transcription factor. Current results warrant research into the use of PSC as nutraceuticals for overall health improvement. PMID- 27381190 TI - Antimicrobial stewardship programs in the critical care setting. PMID- 27381189 TI - Gone for good? An online survey of emigrant health professionals using Facebook as a recruitment tool. AB - BACKGROUND: Health professionals, particularly doctors, nurses and midwives, are in high demand worldwide. Therefore, it is important to assess the future plans and likelihood of return of emigrating health professionals. Nevertheless, health professionals are, by definition, a difficult population to track/survey. This exploratory study reports on the migration intentions of a sample of doctors, nurses and midwives who had emigrated from Ireland, a high-income country which has experienced particularly high outward and inward migration of health professionals since the year 2000. METHODS: Health professionals who had emigrated from Ireland were identified via snowball sampling through Facebook and invited to complete a short online survey composed of closed and open response questions. RESULTS: A total of 388 health professionals (307 doctors, 73 nurses and 8 midwives) who had previously worked in Ireland completed the survey. While over half had originally intended to spend less than 5 years in their destination country at the time of emigration, these intentions changed over time, with the desire to remain abroad on a permanent basis increasing from 10 to 34 % of doctor respondents. Only a quarter of doctors and a half of nurses and midwives intended to return to practice in Ireland in the future. CONCLUSIONS: The longer health professionals remain abroad, the less likely they are to return to their home countries. Countries should focus on the implementation of retention strategies if the 'carousel' of brain drain is to be interrupted. This would allow source countries to benefit from their investments in training health professionals, rather than relying on international recruitment to meet health system staffing needs. Improved data collection systems are also needed to track the migratory patterns and changing intentions of health professionals. Meanwhile, social networking platforms offer alternative methods of filling this information gap. PMID- 27381191 TI - A Single Chance to Contact Multiple Targets: Distinct Osteocyte Morphotypes Shed Light on the Cellular Mechanism Ensuring the Robust Formation of Osteocytic Networks. AB - The formation of the complex osteocytic network relies on the emission of long cellular processes involved in communication, mechanical strain sensing, and bone turnover control. Newly deposited osteocytic processes rapidly become trapped within the calcifying matrix, and, therefore, they must adopt their definitive conformation and contact their targets in a single morphogenetic event. However, the cellular mechanisms ensuring the robustness of this unique mode of morphogenesis remain unknown. To address this issue, we examined the developing calvaria of the amphibian Xenopus tropicalis by confocal, two-photon, and super resolution imaging, and described flattened osteocytes lying within a woven bone structured in lamellae of randomly oriented collagen fibers. While most cells emit peripheral and perpendicular processes, we report two osteocytes morphotypes, located at different depth within the bone matrix and exhibiting distinct number and orientation of perpendicular cell processes. We show that this pattern is conserved with the chick Gallus gallus and suggest that the cellular microenvironment, and more particularly cell-cell contact, plays a fundamental role in the induction and stabilization of osteocytic processes. We propose that this intrinsic property might have been evolutionarily selected for its ability to robustly generate self-organizing osteocytic networks harbored by the wide variety of bone shapes and architectures found in extant and extinct vertebrates. PMID- 27381192 TI - Surface-enhanced resonance Raman scattering of hemoproteins and those in complicated biological systems. AB - In this review article, we discuss surface-enhanced resonance Raman scattering (SERRS) studies of hemeproteins such as myoglobin, hemoglobin, and cytochrome on various metal substrates; for example, colloidal silver nanoparticles coated with and without self-assembled monolayers (SAM), a roughened silver electrode protected with and without SAM, a sharp silver tip, and colloidal gold nanoparticles coated with and without SAM. Moreover, we classify the studies in terms of an excitation wavelength; namely, excitation at the B- (Soret) band, Q- (alpha and beta) band, and in the near infrared (NIR) range. In the SERRS studies with B band excitation, it has been shown that the hemeprotein on a silver surface takes a non-native form through detachment from the heme pocket in the protein. With Q band excitation, on the other hand, the change in SERRS has been explained by the orientation of the hemeprotein on the surface. Even by excitation in the NIR range, the peak positions are consistent with the assignment of the major vibrational modes of heme despite there being no resonance Raman effect. Thus, the SERRS of hemeproteins is influenced by a resonance Raman effect, LSPR, and interactions with the metal surface such as structural changes, orientation, and selective adsorption. Moreover, we discuss how SERRS has been applied to complicated biological systems such as living cells containing hemeprotein. For mitochondria, a change of the oxidation-state was observed by the electron transport chain in the cell and at different positions. As an example of a biomedical application of SERRS, the sensitive detection of malaria is presented. PMID- 27381193 TI - Authorship-who goes first? PMID- 27381194 TI - In Memoriam: John M. King (1927-2016). PMID- 27381195 TI - Caecum location in laboratory rats and mice: an anatomical and radiological study. AB - Intraperitoneal (i.p.) injection is the most frequently used method for implementing parenteral therapies in rats and mice. Whether the caecum is located in the right caudal quadrant or left caudal quadrant in the abdominal cavity is not clear. For that reason, we have developed a method for identifying the location of the caecum in rats and mice and thus revealed the most reliable location for i.p. injection in these animals. Two hundred Wistar albino rats and 100 BALB/c mice were used. The location of the caecum was determined by revealing the intra-abdominal organs immediately following euthanasia, photographing the organs, and archiving the images. Both digital photographic images and computed tomographic (CT) sections were analysed in terms of caecum morphology and location. In both rats and mice, the caecum was most commonly located on the animal's left side. It was less frequently located on the right side or in the centre. The caecum was typically comma-shaped, but it was round or S-shaped in some animals. The direction of rotation of the caecum from the basis to the apex was mostly counterclockwise. Additionally, the apex showed a tendency to be evenly centred. This study demonstrated that the caecum was mostly located on the animal's left side; and for that reason, the most suitable location for i.p. injection in these animals was understood to be the right caudal quadrant. Furthermore, when we compared the CT images and autopsy findings, the caecum did not change location in the abdominal cavity postmortem. PMID- 27381196 TI - Health groups demand closure of Europe's coal fired power stations. PMID- 27381197 TI - Geodermatophilus pulveris sp. nov., a gamma-radiation-resistant actinobacterium isolated from the Sahara desert. AB - A black-pigmented, aerobic actinobacterium, tolerant to ionizing radiation, designated BMG 825T, was isolated from desert limestone dust in Tunisia. The strain grew within the temperature range 10-40 degrees C, at pH 5.5-11.0 and in the presence of 2 % NaCl. The DNA G+C content was 75.7 mol%, and its cell-wall peptidoglycan contained meso-diaminopimelic acid. Sugars of whole-cell hydrolysates were galactose, glucose, and trace amounts of ribose and mannose. The predominant menaquinone was MK-9(H4), and the major fatty acids were iso-C16 : 0 and C16 : 1omega7c. The polar lipid profile comprised phosphatidylcholine, phosphatidylinositol, diphosphatidylglycerol, phosphatidylethanolamine, hydroxyphosphatidylethanolamine and an unspecified glycolipid. 16S rRNA gene sequence analysis revealed that the strain fell into the genus Geodermatophilus, showing the highest similarity with Geodermatophilus poikilotrophus DSM 44209T (99.1 %). DNA-DNA hybridization results, phylogenetic distinctiveness and phenotypic properties supported the classification of this strain as a representative of a novel species of the genus Geodermatophilus, for which the name Geodermatophilus pulveris sp. nov. is proposed. The type strain is BMG 825T (=CECT 9003T=DSM 46839?T). PMID- 27381198 TI - Implementing the Code of Practice on International Recruitment in Romania - exploring the current state of implementation and what Romania is doing to retain its domestic health workforce. AB - BACKGROUND: The Romanian health system is struggling to retain its health workers, who are currently facing strong incentives for migration to Western European health systems. Retention issues, coupled with high levels of migration, complicate Romania's efforts in providing basic health services for rural, underserved, and marginalized populations, as well as in achieving equitable health access for all. The WHO Global Code of Practice on International Recruitment of Health Personnel (the Code) aims to promote ethical international recruitment and health systems strengthening. We explore Romania's implementation of the Code's principles and recommendations. METHODS: We analysed peer-reviewed and grey literature, in English and Romanian, and sought secondary data from the websites of Romania's largest medical universities. The analysis was guided by the following themes and recommendations in the Code: health personnel development and health systems sustainability, international cooperation, data gathering, information exchange, and implementation and monitoring of the Code. RESULTS: Romania's implementation of the Code was observed to be limited. Gaps were identified with regards to several aspects of the Romanian health system, including the lack of support to health personnel training, recruitment, and retention in order to increase the appeal for health providers to practice in Romania and in underserved areas. In terms of international cooperation, the Code recommends various policy instruments to guide recruitment, including bilateral agreements. However, we could not determine which of these instruments were used as a result of the Code and whether or not they were effective. We identified little evidence of initiatives for health workers' professional and personal support. Insufficient data and few information exchange platforms exist on health workforce issues, hindering active sharing of data on migration with European Union and WHO audiences. We could not identify any evidence of monitoring of the Code's implementation to date. CONCLUSIONS: In the absence of major system reforms, health workers will continue to migrate to urban areas and abroad. Romanian policymakers should address more of the Code's recommendations by developing a national policy for human resources for health, a central database to aid health workforce planning and management, stronger platforms for information exchange and civil society engagement, and updated and transparent bilateral agreements. PMID- 27381199 TI - Interleukin-13 Inhibits Expression of cyp27b1 in Peripheral CD14+ Cells That Is Correlated With Vertebral Bone Mineral Density of Patients With Ulcerative Colitis. AB - Osteoporosis is a common problem in aged people and those with related diseases, such as inflammatory bowel diseases. Deregulation of vitamin D metabolism plays a role in the pathogenesis of osteoporosis. Micro RNA (miR) can regulate cytokine expression in cells. This study test a hypothesis that inflammatory cytokine interleukin (IL)-13 increases miR-19a to compromise cyp27b1 (a vitamin D hydroxylase) in peripheral CD14+ cells. Bone mineral density of L2-L4 was measured in 20 patients with ulcerative colitis (UC) and 20 healthy subjects. Peripheral CD14+ cells were isolated from healthy people and patients with UC. Expression of cyp27b1 by CD14+ cells was analyzed in the presence or absence of IL-13 in the culture. We observed that bone mineral density (BMD) in UC patients was significantly lower than healthy subjects. The BMD is negatively correlated with miR-19a in peripheral CD14+ cells. MiR-19a in peripheral CD14+ cell was correlated with serum IL-13 in UC patients. Expression of cyp27b1 in peripheral CD14+ cells was correlated with miR-19a and serum IL-13 in UC patients. IL-13 suppressed cyp27b1 expression in CD14+ cells. IL-13 increased expression of miR 19a in CD14+ cells. IL-13 suppresses cyp27b1 expression in peripheral CD14+ cells via up regulating miR-19a expression. J. Cell. Biochem. 118: 376-381, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27381200 TI - Comparison of Hydrogen and Gold Bonding in [XHX](-) , [XAuX](-) , and Isoelectronic [NgHNg](+) , [NgAuNg](+) (X=Halogen, Ng=Noble Gas). AB - Quantum chemical calculations at the MP2/aug-cc-pVTZ and CCSD(T)/aug-cc-pVTZ levels have been carried out for the title compounds. The electronic structures were analyzed with a variety of charge and energy partitioning methods. All molecules possess linear equilibrium structures with Dinfinityh symmetry. The total bond dissociation energies (BDEs) of the strongly bonded halogen anions [XHX](-) and [XAuX](-) decrease from [FHF](-) to [IHI](-) and from [FAuF](-) to [IAuI](-) . The BDEs of the noble gas compounds [NgHNg](+) and [NgAuNg](+) become larger for the heavier atoms. The central hydrogen and gold atoms carry partial positive charges in the cations and even in the anions, except for [IAuI](-) , in which case the gold atom has a small negative charge of -0.03 e. The molecular electrostatic potentials reveal that the regions of the most positive or negative charges may not agree with the partial charges of the atoms, because the spatial distribution of the electronic charge needs to be considered. The bonding analysis with the QTAIM method suggests a significant covalent character for the hydrogen bonds to the noble gas atoms in [NgHNg](+) and to the halogen atoms in [XHX](-) . The covalent character of the bonding in the gold systems [NgAuNg](+) and [XAuX](-) is smaller than in the hydrogen compound. The energy decomposition analysis suggests that the lighter hydrogen systems possess dative bonds X(-) >H(+) <-X(-) or Ng->H(+) <-Ng while the heavier homologues exhibit electron sharing through two-electron, three-center bonds. Dative bonds X(-) ->Au(+) <-X( ) and Ng->Au(+) <-Ng are also diagnosed for the lighter gold systems, but the heavier compounds possess electron-shared bonds. PMID- 27381201 TI - Extracorporeal Membrane Oxygenation for ARDS: National Trends in the United States 2008-2012. AB - INTRODUCTION: Recent advances in technology and protocols have made the use of extracorporeal membrane oxygenation (ECMO) a viable rescue therapy for patients with ARDS who present with refractory hypoxemia. Despite the lack of strong evidence supporting the use of ECMO in ARDS, its use seems to be increasing. We sought to determine recent trends in the use of ECMO for ARDS. We also assessed trends in mortality among patients with ARDS in whom ECMO was used. METHODS: We performed a retrospective analysis using the largest all-payer in-patient healthcare database in the United States, the Healthcare Cost and Utilization project, the National In-patient Sample database from 2008 to 2012. Subjects with ARDS were identified using carefully chosen International Classification of Diseases, Ninth Revision codes. RESULTS: We found that in 2008, about 1 in 1,000 subjects with ARDS underwent ECMO. Over the subsequent 4-y time period, there was a 0.19% absolute increase and 70% relative increase in the use of ECMO for ARDS. The mortality rate among subjects with ARDS in whom ECMO was used declined from 78% in 2008 to 64% in 2012. We also found a trend toward a reduction in hospital stay among survivors. CONCLUSION: In the United States, between 2008 and 2012, there was an increasing trend toward the use of ECMO in patients with ARDS that coincided with a slight increase in survival among these patients. PMID- 27381202 TI - Exploring the Benefits to Caregivers of a Family-Oriented Pulmonary Rehabilitation Program. AB - BACKGROUND: COPD is a highly incapacitating disease, particularly among older people, implying significant burden for family caregivers. Involving caregivers in comprehensive pulmonary rehabilitation programs might benefit their functional coping to care demands; however, there is no objective evidence to sustain such assumption. This study is a secondary analysis aiming to analyze the effects of a family-based pulmonary rehabilitation program on close family caregivers of older subjects with COPD. METHODS: This is a mixed-method study. Family caregivers were randomly assigned to family-based (experimental) or conventional (control) pulmonary rehabilitation. Caregivers from the family-based pulmonary rehabilitation (n = 20; 80.0% female; age 63.1 +/- 9.5 y) attended the psychoeducational component together with their relatives. In the conventional pulmonary rehabilitation, caregivers did not participate (n = 19; 68.4% female; age 53.6 +/- 11.3 y). Self-rated instruments (Family Crisis Oriented Personal Scales, Depression Anxiety and Stress Scales, and Carers' Assessment of Difficulties Index) and focus group interviews were used to assess the intervention. RESULTS: Caregivers from the family-based pulmonary rehabilitation had significantly greater improvements in overall family coping (P = .01), reframing (P = .01), seeking spiritual support (P = .01), and mobilizing to acquire help (P = .02). No significant differences were found for emotional state. Significant improvements in overall burden (P = .01), reactions to caregiving (P = .01), physical demands of caring (P = .044), and poor family support (P = .038) were observed, although there were no significant between group differences. Qualitative data sustained the benefits of involving family caregivers in pulmonary rehabilitation. CONCLUSIONS: The findings provide valuable evidence to recommend the inclusion of COPD family caregivers in comprehensive pulmonary rehabilitation. Family-oriented pulmonary rehabilitation maximizes caregivers' adaptive coping and potentially prevents negative psychological outcomes; however, further research is needed. PMID- 27381203 TI - Impact of an Electronic Medical Record Screening Tool and Therapist-Driven Protocol on Length of Stay and Hospital Readmission for COPD. AB - BACKGROUND: In the United States, care for COPD patients is frequently delivered by respiratory therapists (RTs). After implementing a therapist-driven protocol for COPD treatment, we sought to improve identification of COPD patients. We hypothesized that using an electronic medical record screening tool to identify subjects with COPD combined with a therapist-driven protocol would positively impact length of stay (LOS) and readmission rates. METHODS: Utilizing the electronic medical record to search the provider's admission notes for the terms COPD/Asthma, a report was generated. Subjects already receiving RT services were removed. An RT evaluated identified subjects using a therapist-driven protocol combining clinical assessment and FEV1 to calculate an air-flow obstruction score. Scores >=7 received 24 h of bronchodilator therapy by RTs. Scores <7 received assessment by RTs but bronchodilator therapy administered by nursing staff. An RT performed medication reconciliation and education for both groups. ICD-9 discharge codes identified primary and secondary diagnoses of COPD. LOS and 30-d readmission rates were measured for a 14-month period. Respiratory-triggered rapid response data were also collected. RESULTS: The pre-intervention period was from December 2013 to June 2014, and the post-intervention period was from July 2014 to January 2015. There were 142 subjects in total, 68 pre-intervention and 74 post-intervention. For primary COPD, mean LOS decreased from 4.37 to 2.96 d (P = .10), and 30-d readmission rates decreased from 13.6 to 6.1%. Respiratory triggered rapid response data were as follows: The pre-intervention span was from January 2014 to June 2014, and post-intervention was from July 2014 to December 2015. For primary COPD, there were 61 pre-intervention subjects and 63 post intervention with a decrease in respiratory-triggered rapid responses from 21 pre intervention (34.4%) to 8 post-intervention (12.7%) (P = .004). For secondary COPD (1,168 pre-intervention, 1,267 post-intervention), there was a change from 318 (27.2%) pre-intervention to 296 (23.4%) post-intervention (P = .03). CONCLUSION: Utilization of the electronic medical record to identify subjects with likely COPD combined with a therapist-driven protocol directed by RT assessment was associated with a trend toward decreased LOS and reduction in readmission rates. There was a significant reduction of respiratory-triggered rapid responses in subjects with a primary diagnosis of COPD. PMID- 27381204 TI - Chronic postsurgical pain and persistent opioid use following surgery: the need for a transitional pain service. AB - AIM: To identify the 3-month incidence of chronic postsurgical pain and long-term opioid use in patients at the Toronto General Hospital. METHODS: 200 consecutive patients presenting for elective major surgery completed standardized questionnaires by telephone at 3 months after surgery. RESULTS: 51 patients reported a preoperative chronic pain condition, with 12 taking opioids preoperatively. 3 months after surgery 35% of patients reported having surgical site pain and 13.5% continued to use opioids for postsurgical pain relief. Postoperative opioid use was associated with interference with walking and work, and lower mood. CONCLUSION: Chronic postsurgical pain and ongoing opioid use are concerns that warrant the implementation of a Transitional Pain Service to modify the pain trajectories and enable effective opioid weaning following major surgery. PMID- 27381205 TI - HIV-1 infection and pregnancy in young women in Brazil: socioeconomic and drug resistance profiles in a cross-sectional study. AB - OBJECTIVES: To describe socioeconomic and antiretroviral (ARV) drug resistance profiles among young pregnant women infected with HIV-1. SETTING: A public health antenatal programme responsible for screening ~90 000 pregnant women per year for nine different infectious diseases in Central Western Brazil. PARTICIPANTS: 96 young pregnant women (15-24 years) infected with HIV-1. PRIMARY AND SECONDARY OUTCOME MEASURES: Standard interviews and blood samples were taken at the time of recruitment, at the first medical appointment after confirmation of diagnosis of HIV-1 infection, and before ARV prophylaxis initiation. Clinical and laboratory data were retrieved from medical files. HIV-1 pol gene sequences (entire protease/PR, partial reverse transcriptase/RT) were obtained from plasma RNA. ARV resistance mutations (CPR/Stanford HIV-1; International AIDS Society-USA databases) were identified. RESULTS: The median age was 21 years; most reported <8 years education; 73% were recently diagnosed. Approximately 20% (19/96) presented late for antenatal care (after 26 gestational weeks), while 49% reported >=2 previous pregnancies. Possible heterosexual transmission by an HIV-1 infected partner (17%) and commercial sex work (2%) were reported. The median of CD4 cell count was 526 cells/mm(3); the median viral load was: 10 056 copies/mL in ARV-naive (48/96) patients and 5881 copies/mL in ARV-exposed (48/96) patients. Two probable seroconversion cases during pregnancy were identified in adolescents. One mother-to-child transmission case (1.0%) was observed. Transmitted drug resistance among ARV-naive patients was 9.3% (CI 95% 3.3% to 19.6%); secondary drug resistance among ARV-exposed patients was 12.5% (CI 95% 4.7% to 25.6%). CONCLUSIONS: Despite high access to antenatal care, the low socioeconomic-educational profiles seen in these young HIV-1-infected women highlight the necessity of improved public health educational and preventive strategies regarding HIV infection and early unplanned pregnancy. PMID- 27381206 TI - Catastrophic health expenditure: a comparative analysis of empty-nest and non empty-nest households with seniors in Shandong, China. AB - OBJECTIVE: The aim of this study was to compare the catastrophic health expenditure (CHE) prevalence and its determinants between empty-nest and non empty-nest elderly households. SETTING: Shandong province of China. PARTICIPANTS: A total of 2761 elderly households are included in the analysis. RESULTS: CHE incidence among elderly households was 44.9%. The CHE incidence of empty-nest singles (59.3%, p=0.000, OR=3.19) and empty-nest couples (52.9%, p=0.000, OR=2.45) are both statistically higher than that of non-empty-nest elderly households (31.4%). An inverse association was observed between CHE incidence and income level in all elderly household types. Factors including 1 or more household elderly members with non-communicable chronic diseases in the past 6 months, 1 or more elderly household members being hospitalised in the past year and lower household income, are significant risk factors for CHE in all 3 household types (p<0.05). Health insurance status was found to be a significant determinant of CHE among empty-nest singles and non-empty-nest households (p<0.05). CONCLUSIONS: CHE incidence among elderly households is high in China. Empty-nest households are at higher risk for CHE than non-empty-nest households. Based on these findings, we suggest that special insurance be developed to broaden the coverage of health services and heighten the reimbursement rate for empty-nest elderly in the existing health insurance schemes. Financial and social protection interventions are also essential for identified at-risk subgroups among different types of elderly households. PMID- 27381207 TI - What are the factors associated with good mental health among Aboriginal children in urban New South Wales, Australia? Phase I findings from the Study of Environment on Aboriginal Resilience and Child Health (SEARCH). AB - OBJECTIVE: To identify the factors associated with 'good' mental health among Aboriginal children living in urban communities in New South Wales, Australia. DESIGN: Cross-sectional survey (phase I of a longitudinal study). SETTING: 4 Aboriginal Community Controlled Health Services that deliver primary care. All services were located in urban communities in New South Wales, Australia. PARTICIPANTS: 1005 Aboriginal children aged 4-17 years who participated in phase I of the Study of Environment on Aboriginal Resilience and Child Health (SEARCH). PRIMARY OUTCOME MEASURE: Carer report version of the Strengths and Difficulties Questionnaire. Scores <17 were considered to indicate 'good' mental health for the purposes of this article. RESULTS: The majority (72%) of SEARCH participants were not at high risk for emotional or behavioural problems. After adjusting for the relative contributions of significant demographic, child and carer health factors, the factors associated with good mental health among SEARCH children were having a carer who was not highly psychologically distressed (OR=2.8, 95% CI 1.6 to 5.1); not suffering from frequent chest, gastrointestinal or skin infections (OR=2.8, 95% CI 1.8 to 4.3); and eating two or more servings of vegetables per day (OR=2.1, 95% CI 1.2 to 3.8). Being raised by a foster carer (OR=0.2, 95% CI 0.01 to 0.71) and having lived in 4 or more homes since birth (OR=0.62, 95% CI 0.39 to 1.0) were associated with significantly lower odds of good mental health. Slightly different patterns of results were noted for adolescents than younger children. CONCLUSIONS: Most children who participated in SEARCH were not at high risk for emotional or behavioural problems. Promising targets for efforts to promote mental health among urban Aboriginal children may include the timely provision of medical care for children and provision of additional support for parents and carers experiencing mental or physical health problems, for adolescent boys and for young people in the foster care system. PMID- 27381208 TI - Incidence and outcomes of emergency self-harm among adolescents: a descriptive epidemiological study in Osaka City, Japan. AB - OBJECTIVES: To evaluate the incidence and outcomes of self-harm from ambulance records. DESIGN: A retrospective, observational study. SETTING: Osaka City, Japan. PARTICIPANTS: A total of 365 adolescents aged 10-19 years with emergency self-harm such as poisoning by drugs or gas, cutting skin, jumping from heights, hanging and drowning and treated by emergency medical service personnel from January 2010 through December 2012. PRIMARY OUTCOME MEASUREMENTS: Incidence per 100 000 persons and outcome at the scene or hospital arrival by age and gender. Poisson regression models for incidence evaluation were used; reporting relative risks (RRs) and their 95% CIs. RESULTS: During the study period, a total of 425 self-harm events were documented in 365 adolescents. The incidence of self-harm increased significantly between the ages of 11 and 19 years, from 6.3 to 81.0 among boys and the ages of 12 and 19 years from 6.3 to 228.3 among girls, respectively (both p<0.001). Although there was no incidence difference between girls and boys in the group aged 11-14 years (RR 1.20; 95% CI 0.59 to 2.47), the incidence was significantly higher among girls than boys in the group aged 15-19 years (RR 4.18; 95% CI 3.20 to 5.45). The overall proportion of death by self harm was 4.9%. The proportion of hospital admission and death by self-harm was higher among boys than among girls (38.6% vs 25.2%, p=0.016 and 14.8% vs 2.4%, p<0.001). CONCLUSIONS: The incidence of emergency treatment for self-harm by adolescents increased with age and our findings also demonstrated the gender paradox. It would be necessary to establish active, gender-specific and comprehensive prevention strategies for adolescent self-harm, based on our findings showing the age and gender differences of self-harm among adolescents. PMID- 27381209 TI - Protocol of the Australasian Malignant Pleural Effusion-2 (AMPLE-2) trial: a multicentre randomised study of aggressive versus symptom-guided drainage via indwelling pleural catheters. AB - INTRODUCTION: Malignant pleural effusions (MPEs) can complicate most cancers, causing dyspnoea and impairing quality of life (QoL). Indwelling pleural catheters (IPCs) are a novel management approach allowing ambulatory fluid drainage and are increasingly used as an alternative to pleurodesis. IPC drainage approaches vary greatly between centres. Some advocate aggressive (usually daily) removal of fluid to provide best symptom control and chance of spontaneous pleurodesis. Daily drainages however demand considerably more resources and may increase risks of complications. Others believe that MPE care is palliative and drainage should be performed only when patients become symptomatic (often weekly to monthly). Identifying the best drainage approach will optimise patient care and healthcare resource utilisation. METHODS AND ANALYSIS: A multicentre, open label randomised trial. Patients with MPE will be randomised 1:1 to daily or symptom-guided drainage regimes after IPC insertion. Patient allocation to groups will be stratified for the cancer type (mesothelioma vs others), performance status (Eastern Cooperative Oncology Group status 0-1 vs >=2), presence of trapped lung (vs not) and prior pleurodesis (vs not). The primary outcome is the mean daily dyspnoea score, measured by a 100 mm visual analogue scale (VAS) over the first 60 days. Secondary outcomes include benefits on physical activity levels, rate of spontaneous pleurodesis, complications, hospital admission days, healthcare costs and QoL measures. Enrolment of 86 participants will detect a mean difference of VAS score of 14 mm between the treatment arms (5% significance, 90% power) assuming a common between-group SD of 18.9 mm and a 10% lost to follow-up rate. ETHICS AND DISSEMINATION: The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study (number 2015-043). Results will be published in peer-reviewed journals and presented at scientific meetings. TRIAL REGISTRATION NUMBER: ACTRN12615000963527; Pre-results. PMID- 27381210 TI - Association between psychological distress and dietary intake among evacuees after the Great East Japan Earthquake in a cross-sectional study: the Fukushima Health Management Survey. AB - OBJECTIVE: Psychological distress is generally associated with poor dietary intake, but this has never been investigated among residents after a major disaster. We attempted to reveal the associations between dietary intake and non specific mental health distress as well as traumatic symptoms among evacuees after the Great East Japan Earthquake of 2011. METHODS: In this cross-sectional analysis of 63 047 evacuees (27 901 men, 35 146 women) who responded to The Fukushima Health Management Survey in 2012, non-specific mental health distress was assessed using the Kessler-6 (K6) scale, while traumatic symptoms were evaluated using the Post-traumatic Stress Disorder (PTSD) Checklist-Stressor Specific Version (PCL-S). The outcome was 'low frequency'-meaning a daily consumption in the 25th centile or less according to the food frequency questionnaire (FFQ)-of 19 targeted food items. Logistic regression analysis was used to estimate ORs and 95% CIs adjusted for demographic, lifestyle-related and disaster-related factors. RESULTS: Of the participants, 14.7% suffered non specific mental health distress, and 21.2% exhibited traumatic symptoms. Multivariable adjusted logistic regression analysis showed that the former were likely to have a low intake frequency of certain foods, such as rice and bread, fish, meat, vegetables or fruit (non-juice), soya bean products, milk, and yogurt or lactobacillus drinks; the latter were also likely to have a low intake frequency of certain foods, including rice and bread, fish, meat, vegetables (non juice), milk and yogurt or lactobacillus drinks, but conversely consumed vegetable and fruit juices more often. These associations between dietary intake and non-specific mental health distress, as well as traumatic symptoms, were predominantly observed in women. CONCLUSIONS: Psychological distress after the Great East Japan Earthquake among evacuees was associated with a low intake frequency of certain foods, and the association was predominantly observed in women. PMID- 27381211 TI - Evaluation of the use of oseltamivir prophylaxis in the control of influenza outbreaks in long-term care facilities in Alberta, Canada: a retrospective provincial database analysis. AB - OBJECTIVES: To evaluate the impact of oseltamivir prophylaxis in the management and control of influenza outbreaks in long-term care facilities in Alberta, Canada. SETTING AND PARTICIPANTS: Long-term care facilities where 127 influenza outbreaks were reported to public health authorities in Alberta, Canada, during two influenza seasons from 2013 to 2015. DESIGN AND OUTCOME MEASURES: Using routinely collected surveillance and administrative data, we examined the association between decision-making time for oseltamivir recommendation as prophylaxis strategy for influenza outbreaks in long-term care facilities (explanatory variable) and the duration of an influenza outbreak, the postprophylaxis risk of influenza-like illness and hospitalisation among residents of long-term care facilities in Alberta (outcome variables) using multivariable linear and Poisson regression models. RESULTS: Oseltamivir prophylaxis decision-making time was positively associated with the postintervention duration of an outbreak, with a 1-day delay in making decision on oseltamivir prophylaxis associated with 2.22 (95% CI 1.37 to 3.06) more days of the duration of an outbreak after controlling for potential confounding effect of the number of residents at risk at intervention, outbreak progression time, prevalence of influenza-like illness during outbreak progression, facility location, presence of mixed strain and based on optimal timing of oseltamivir prophylaxis. Although not statistically significant, a 1-day delay in making decision on oseltamivir prophylaxis was associated with a 5% (95% CI -1% to 11%) increase in the postintervention risk of influenza-like illness, and a 6% (95% CI -8% to 22%) increase in the postintervention risk of hospitalisation after controlling for the same potential confounders. CONCLUSIONS: Our study demonstrated benefits of using oseltamivir prophylaxis to shorten the duration of influenza outbreaks; however, there were no significant differences in the influenza-like illness and hospitalisation risk occurring after the intervention. Surveillance data may offer means of rapid evaluation of oseltamivir prophylaxis in long-term care facilities as a public health measure. PMID- 27381212 TI - Interventions addressing risk factors of ischaemic heart disease in sub-Saharan Africa: a systematic review. AB - BACKGROUND: Ischaemic heart disease (IHD) is currently ranked eighth among the leading causes of deaths in sub-Saharan Africa (sSA). Yet, effective population wide preventive measures targeting risks in the region are still largely unavailable. We aimed to review population-wide and individual-level interventions addressing risk factors of IHD among adults in sSA. METHODS: A systematic search of MEDLINE, EMBASE, Global Health and AJOL was conducted to identify studies focusing on population-wide and individual-level interventions targeting risks of IHD among adults in sSA. We conducted a detailed synthesis of basic findings of selected studies. RESULTS: A total of 2311 studies were identified, with only 9 studies meeting our selection criteria. 3 broad interventions were identified: dietary modifications, physical activity and community-based health promotion measures on tobacco and alcohol cessation. 3 studies reported significant reduction in blood pressure (BP), and another study reported statistically significant reduction in mean total cholesterol. Other outcome measures observed ranged from mild to no reduction in BP, blood glucose, body mass index and total cholesterol, respectively. CONCLUSIONS: We cannot specify with all certainty contextually feasible interventions that can be effective in modifying IHD risk factors in population groups across sSA. We recommend more research on IHD, particularly on the understanding of the burden, geared towards developing and/or strengthening preventive and treatment interventions for the disease in sSA. PMID- 27381213 TI - Identifying process and outcome indicators of successful transitions from child to adult mental health services: protocol for a scoping review. AB - INTRODUCTION: A significant proportion of youth need to transition from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS); however, the transition process is not well understood and often experienced poorly by youth. In the effort to design and evaluate standards of practice for transitions, there is a need to identify key elements of a successful transition. The objectives of this scoping review are to: (1) identify definitions of successful transitions from CAMHS to AMHS; and (2) identify indicators that have been used to measure CAMHS-AMHS transition care processes and quality, and outcomes. METHODS: We will search 8 electronic bibliographic databases from 1980 to 2016 (eg, Medline, EMBASE, PsycINFO), professional associations, policy documents, and other grey literature to identify relevant material. We will include experimental, quasi-experimental, observational studies, and non-research studies (guidelines, narrative reviews, policy documents) examining the transition from CAMHS to AMHS. 2 raters will independently screen each retrieved title and abstract for eligibility using the study inclusion criteria (level 1), and then will independently assess full-text articles to determine if these meet the inclusion criteria (level 2). Data extraction will be completed and results will be synthesised both quantitatively and qualitatively. ETHICS AND DISSEMINATION: The results of the scoping review will be used to develop a set of indicators that will be prioritised and evaluated in a Delphi consensus study. This will serve as a foundation for the development of the first instrument to assess the quality and success of CAMHS-AMHS transitions. Ethics approval is not required for this scoping study. PMID- 27381216 TI - Erratum to: Serological makers of rubella infection in Africa in the pre vaccination era: a systematic review. PMID- 27381214 TI - PLAG1 expression is maintained in recurrent pleomorphic adenoma. AB - The proto-oncogene (pleomorphic adenoma gene 1 (PLAG1)) is immunohistochemically overexpressed in pleomorphic adenoma (PA). Its expression in recurrent pleomorphic adenoma (RPA), however, has not been investigated. Since complex mechanisms are involved in tumor recurrence, the aim of this study was to investigate whether PLAG1 overexpression occurs in RPA. We studied PLAG1 protein expression in 40 PAs and 36 RPAs by immunohistochemistry. Cases with immunopositive cells were classified into two categories, between 10 and 50 % and >50 %. In both groups, PLAG1 expression was observed in both epithelial and myoepithelial cells. Of PAs, 37 cases (93 %) were positive, while this was the case in 34 RPA cases (94 %). Our findings suggest that in addition to morphological similarity, PA and RPA express PLAG1, which might play a role in tumor recurrence. Furthermore, as for PA, expression of PLAG1 can be considered a valuable diagnostic marker for RPA. PMID- 27381215 TI - Efficient nucleic acid delivery to murine regulatory T cells by gold nanoparticle conjugates. AB - Immune responses have to be tightly controlled to guarantee maintenance of immunological tolerance and efficient clearance of pathogens and tumorigenic cells without induction of unspecific side effects. CD4(+) CD25(+) regulatory T cells (Tregs) play an important role in these processes due to their immunosuppressive function. Genetic modification of Tregs would be helpful to understand which molecules and pathways are involved in their function, but currently available methods are limited by time, costs or efficacy. Here, we made use of biofunctionalized gold nanoparticles as non-viral carriers to transport genetic information into murine Tregs. Confocal microscopy and transmission electron microscopy revealed an efficient uptake of the bioconjugates by Tregs. Most importantly, coupling eGFP-siRNA to those particles resulted in a dose and time dependent reduction of up to 50% of eGFP expression in Tregs isolated from Foxp3eGFP reporter mice. Thus, gold particles represent a suitable carrier for efficient import of nucleic acids into murine CD4(+) CD25(+) Tregs, superior to electroporation. PMID- 27381217 TI - The S128N mutation combined with an additional potential N-linked glycosylation site at residue 133 in hemagglutinin affects the antigenicity of the human H7N9 virus. PMID- 27381219 TI - Increasing genetic diversity of Zika virus in the Latin American outbreak. PMID- 27381218 TI - Astrovirus VA1 identified by next-generation sequencing in a nasopharyngeal specimen of a febrile Tanzanian child with acute respiratory disease of unknown etiology. PMID- 27381220 TI - Effects of protein transduction domain (PTD) selection and position for improved intracellular delivery of PTD-Hsp27 fusion protein formulations. AB - Protein drugs have attracted considerable attention as therapeutic agents due to their diversity and biocompatibility. However, hydrophilic proteins possess difficulty in penetrating lipophilic cell membrane. Although protein transduction domains (PTDs) have shown effectiveness in protein delivery, the importance of selection and position of PTDs in recombinant protein vector constructs has not been investigated. This study intends to investigate the significance of PTD selection and position for therapeutic protein delivery. Heat shock protein 27 (Hsp27) would be a therapeutic protein for the treatment of ischemic heart diseases, but itself is insufficient to prevent systemic degradation and overcoming biochemical barriers during cellular transport. Among all PTD-Hsp27 fusion proteins we cloned, Tat-Hsp27 fusion protein showed the highest efficacy. Nona-arginine (9R) conjugation to the N-terminal of Hsp27 (Hsp27-T) showed higher efficacy than C-terminal. To test the synergistic effect of two PTDs, Tat was inserted to the N-terminal of Hsp27-9R. Tat-Hsp27-9R exhibited enhanced transduction efficiency and significant improvement against oxidative stress and apoptosis. PTD-Hsp27 fusion proteins have strong potential to be developed as therapeutic proteins for the treatment of ischemic heart diseases and selection and position of PTDs for improved efficacy of PTD-fusion proteins need to be optimized considering protein's nature, transduction efficiency and stability. PMID- 27381221 TI - Interobserver agreement of radiologists assessing the response of rectal cancers to preoperative chemoradiation using the MRI tumour regression grading (mrTRG). AB - AIM: To investigate whether the magnetic resonance imaging (MRI) tumour regression grading (mrTRG) scale can be taught effectively resulting in a clinically reasonable interobserver agreement (>0.4; moderate to near perfect agreement). MATERIALS AND METHODS: This study examines the interobserver agreement of mrTRG, between 35 radiologists and a central reviewer. Two workshops were organised for radiologists to assess regression of rectal cancers on MRI staging scans. A range of mrTRGs on 12 patient scans were used for assessment. RESULTS: Kappa agreement ranged from 0.14-0.82 with a median value of 0.57 (95% CI: 0.37-0.77) indicating good overall agreement. Eight (26%) radiologists had very good/near perfect agreement (kappa>0.8). Six (19%) radiologists had good agreement (0.8>=kappa>0.6) and a further 12 (39%) had moderate agreement (0.6>=kappa>0.4). Five (16%) radiologists had a fair agreement (0.4>=kappa>0.2) and two had poor agreement (0.2>kappa). There was a tendency towards good agreement (skewness: 0.92). In 65.9% and 90% of cases the radiologists were able to correctly highlight good and poor responders, respectively. CONCLUSIONS: The assessment of the response of rectal cancers to chemoradiation therapy may be performed effectively using mrTRG. Radiologists can be taught the mrTRG scale. Even with minimal training, good agreement with the central reviewer along with effective differentiation between good and intermediate/poor responders can be achieved. Focus should be on facilitating the identification of good responders. It is predicted that with more intensive interactive case-based learning a kappa>0.8 is likely to be achieved. Testing and retesting is recommended. PMID- 27381222 TI - Protein Kinase G facilitates EGFR-mediated cell death in MDA-MB-468 cells. AB - The Epidermal Growth Factor Receptor (EGFR) is a transmembrane receptor tyrosine kinase with critical implications in cell proliferation, migration, wound healing and the regulation of apoptosis. However, the EGFR has been shown to be hyper expressed in a number of human malignancies. The MDA-MB-468 metastatic breast cell line is one example of this. This particular cell line hyper-expresses the EGFR and undergoes EGFR-mediated apoptosis in response to EGF ligand. The goal of this study was to identify the kinases that could be potential intermediates for the EGFR-mediated induction of apoptosis intracellularly. After identifying Cyclic GMP-dependent Protein Kinase G (PKG) as a plausible intermediate, we wanted to determine the temporal relationship of these two proteins in the induction of apoptosis. We observed a dose-dependent decrease in MDA-MB-468 cell viability, which was co-incident with increased PKG activity as measured by VASPSer239 phosphorylation. In addition, we observed a dose dependent decrease in cell viability, as well as an increase in apoptosis, in response to two different PKG agonists, 8-Bromo-cGMP and 8-pCPT-cGMP. MDA-MB-468 cells with reduced PKG activity had attenuated EGFR-mediated apoptosis. These findings indicate that PKG does not induce cell death via transphosphorylation of the EGFR. Instead, PKG activity occurs following EGFR activation. Together, these data indicate PKG as an intermediary in EGFR-mediated cell death, likely via apoptotic pathway. PMID- 27381223 TI - Cell behaviors and dynamics during angiogenesis. AB - Vascular networks are formed and maintained through a multitude of angiogenic processes, such as sprouting, anastomosis and pruning. Only recently has it become possible to study the behavior of the endothelial cells that contribute to these networks at a single-cell level in vivo This Review summarizes what is known about endothelial cell behavior during developmental angiogenesis, focusing on the morphogenetic changes that these cells undergo. PMID- 27381225 TI - Dental mesenchymal stem cells. AB - Mammalian teeth harbour mesenchymal stem cells (MSCs), which contribute to tooth growth and repair. These dental MSCs possess many in vitro features of bone marrow-derived MSCs, including clonogenicity, expression of certain markers, and following stimulation, differentiation into cells that have the characteristics of osteoblasts, chondrocytes and adipocytes. Teeth and their support tissues provide not only an easily accessible source of MSCs but also a tractable model system to study their function and properties in vivo In addition, the accessibility of teeth together with their clinical relevance provides a valuable opportunity to test stem cell-based treatments for dental disorders. This Review outlines some recent discoveries in dental MSC function and behaviour and discusses how these and other advances are paving the way for the development of new biologically based dental therapies. PMID- 27381224 TI - Generation of intestinal surface: an absorbing tale. AB - The vertebrate small intestine requires an enormous surface area to effectively absorb nutrients from food. Morphological adaptations required to establish this extensive surface include generation of an extremely long tube and convolution of the absorptive surface of the tube into villi and microvilli. In this Review, we discuss recent findings regarding the morphogenetic and molecular processes required for intestinal tube elongation and surface convolution, examine shared and unique aspects of these processes in different species, relate these processes to known human maladies that compromise absorptive function and highlight important questions for future research. PMID- 27381226 TI - Fat4-Dchs1 signalling controls cell proliferation in developing vertebrae. AB - The protocadherins Fat4 and Dchs1 act as a receptor-ligand pair to regulate many developmental processes in mice and humans, including development of the vertebrae. Based on conservation of function between Drosophila and mammals, Fat4 Dchs1 signalling has been proposed to regulate planar cell polarity (PCP) and activity of the Hippo effectors Yap and Taz, which regulate cell proliferation, survival and differentiation. There is strong evidence for Fat regulation of PCP in mammals but the link with the Hippo pathway is unclear. In Fat4(-/-) and Dchs1(-/-) mice, many vertebrae are split along the midline and fused across the anterior-posterior axis, suggesting that these defects might arise due to altered cell polarity and/or changes in cell proliferation/differentiation. We show that the somite and sclerotome are specified appropriately, the transcriptional network that drives early chondrogenesis is intact, and that cell polarity within the sclerotome is unperturbed. We find that the key defect in Fat4 and Dchs1 mutant mice is decreased proliferation in the early sclerotome. This results in fewer chondrogenic cells within the developing vertebral body, which fail to condense appropriately along the midline. Analysis of Fat4;Yap and Fat4;Taz double mutants, and expression of their transcriptional target Ctgf, indicates that Fat4-Dchs1 regulates vertebral development independently of Yap and Taz. Thus, we have identified a new pathway crucial for the development of the vertebrae and our data indicate that novel mechanisms of Fat4-Dchs1 signalling have evolved to control cell proliferation within the developing vertebrae. PMID- 27381227 TI - YAP stabilizes SMAD1 and promotes BMP2-induced neocortical astrocytic differentiation. AB - ?YAP (yes-associated protein), a key transcriptional co-factor that is negatively regulated by the Hippo pathway, is crucial for the development and size control of multiple organs, including the liver. However, its role in the brain remains unclear. Here, we provide evidence for YAP regulation of mouse neocortical astrocytic differentiation and proliferation. YAP was undetectable in neurons, but selectively expressed in neural stem cells (NSCs) and astrocytes. YAP in NSCs was required for neocortical astrocytic differentiation, with no apparent role in self-renewal or neural differentiation. However, YAP in astrocytes was necessary for astrocytic proliferation. Yap (Yap1) knockout, Yap(nestin) conditional knockout and Yap(GFAP) conditional knockout mice displayed fewer neocortical astrocytes and impaired astrocytic proliferation and, consequently, death of neocortical neurons. Mechanistically, YAP was activated by BMP2, and the active/nuclear YAP was crucial for BMP2 induction and stabilization of SMAD1 and astrocytic differentiation. Expression of SMAD1 in YAP-deficient NSCs partially rescued the astrocytic differentiation deficit in response to BMP2. Taken together, these results identify a novel function of YAP in neocortical astrocytic differentiation and proliferation, and reveal a BMP2-YAP-SMAD1 pathway underlying astrocytic differentiation in the developing mouse neocortex. PMID- 27381231 TI - Statistical detection of nanoparticles in cells by darkfield microscopy. AB - In the fields of nanomedicine, biophotonics and radiation therapy, nanoparticle (NP) detection in cell models often represents a fundamental step for many in vivo studies. One common question is whether NPs have or have not interacted with cells. In this context, we propose an imaging based technique to detect the presence of NPs in eukaryotic cells. Darkfield images of cell cultures at low magnification (10*) are acquired in different spectral ranges and recombined so as to enhance the contrast due to the presence of NPs. Image analysis is applied to extract cell-based parameters (i.e. mean intensity), which are further analyzed by statistical tests (Student's t-test, permutation test) in order to obtain a robust detection method. By means of a statistical sample size analysis, the sensitivity of the whole methodology is quantified in terms of the minimum cell number that is needed to identify the presence of NPs. The method is presented in the case of HeLa cells incubated with gold nanorods labeled with anti-CA125 antibodies, which exploits the overexpression of CA125 in ovarian cancers. Control cases are considered as well, including PEG-coated NPs and HeLa cells without NPs. PMID- 27381228 TI - Retinal determination genes coordinate neuroepithelial specification and neurogenesis modes in the Drosophila optic lobe. AB - Differences in neuroepithelial patterning and neurogenesis modes contribute to area-specific diversifications of neural circuits. In the Drosophila visual system, two neuroepithelia, the outer (OPC) and inner (IPC) proliferation centers, generate neuron subtypes for four ganglia in several ways. Whereas neuroepithelial cells in the medial OPC directly convert into neuroblasts, in an IPC subdomain they generate migratory progenitors by epithelial-mesenchymal transition that mature into neuroblasts in a second proliferative zone. The molecular mechanisms that regulate the identity of these neuroepithelia, including their neurogenesis modes, remain poorly understood. Analysis of Polycomblike revealed that loss of Polycomb group-mediated repression of the Hox gene Abdominal-B (Abd-B) caused the transformation of OPC to IPC neuroepithelial identity. This suggests that the neuroepithelial default state is IPC-like, whereas OPC identity is derived. Ectopic Abd-B blocks expression of the highly conserved retinal determination gene network members Eyes absent (Eya), Sine oculis (So) and Homothorax (Hth). These factors are essential for OPC specification and neurogenesis control. Finally, eya and so are also sufficient to confer OPC-like identity, and, in parallel with hth, the OPC-specific neurogenesis mode on the IPC. PMID- 27381232 TI - Development and evaluation of an enhanced diabetes prevention program with psychosocial support for urban American Indians and Alaska natives: A randomized controlled trial. AB - Diabetes is highly prevalent, affecting over 25 million adults in the US, yet it can be effectively prevented through lifestyle interventions, including the well tested Diabetes Prevention Program (DPP). American Indian/Alaska Native (AIAN) adults, the majority of whom live in urban settings, are more than twice as likely to develop diabetes as non-Hispanic whites. Additionally, prevalent mental health issues and psychosocial stressors may facilitate progression to diabetes and hinder successful implementation of lifestyle interventions for AIAN adults. This 2-phased study first engaged community stakeholders to develop culturally tailored strategies to address mental health concerns and psychosocial stressors. Pilot testing (completed) refined those strategies that increase engagement in an enhanced DPP for urban AIAN adults. Second, the enhanced DPP will be compared to a standard DPP in a randomized controlled trial (ongoing) with a primary outcome of body mass index (BMI) and a secondary outcome of quality of life (QoL) over 12months. Obese self-identified AIAN adults residing in an urban setting with one or more components of the metabolic syndrome (excluding waist circumference) will be randomized to the enhanced or standard DPP (n=204). We hypothesize that addressing psychosocial barriers within a culturally-tailored DPP will result in clinical (BMI) and superior patient-centered (QoL) outcomes as compared to a standard DPP. Exploratory outcomes will include cardiometabolic risk factors (e.g., waist circumference, blood pressure, fasting glucose) and health behaviors (e.g., diet, physical activity). Results of this trial may be applicable to other urban AIAN or minority communities or even diabetes prevention in general. PMID- 27381233 TI - Identification and characterization of photodegradation products of metoprolol in the presence of natural fulvic acid by HPLC-UV-MSn. AB - Metoprolol is a beta-blocker highly prescribed for the treatment of heart diseases. It is not efficiently removed in wastewater treatment plants and it has been detected not only in the treated effluents, but also in natural waters. Thus, the knowledge of its fate in the environment is an important issue, and photodegradation is an important degradation pathway. While direct photodegradation of metoprolol by solar light is not relevant, there is evidence in the literature that it suffers indirect photodegradation and a few studies have been published showing the important role of dissolved humic matter as photo sensitizer. However, the identification of the photoproducts formed in the presence of humic matter is very poor, since only 2 photoproducts had been identified. This study investigated the degradation of metoprolol under simulated solar radiation and in the presence of fulvic acids (FA) extracted from a river. During the photodegradation experiments we observed the formation of new compounds which were separated and tentatively identified by HPLC-UV-ESI-MSn. At least 16 compounds were tentatively identified, including the 2 compounds previously identified in the literature and 4 new compounds which had not been detected by other authors as degradation products of metoprolol, even when submitted to artificial degradation processes. PMID- 27381234 TI - Transformation of ranitidine during water chlorination and ozonation: Moiety specific reaction kinetics and elimination efficiency of NDMA formation potential. AB - Ranitidine can produce high yields of N-nitrosodimethylamine (NDMA) upon chloramination and its presence in water resources is a concern for water utilities using chloramine disinfection. This study assessed the efficiency of water chlorination and ozonation in transforming ranitidine and eliminating its NDMA formation potential (NDMA-FP) by determining moiety-specific reaction kinetics, stoichiometric factors, and elimination levels in real water matrices. Despite the fact that chlorine reacts rapidly with the acetamidine and thioether moieties of ranitidine (k>10(8)M(-1)s(-1) at pH 7), the NDMA-FP decreases significantly only when chlorine reacts with the less reactive tertiary amine (k=3*10(3)M(-1)s(-1) at pH 7) or furan moiety (k=81M(-1)s(-1) at pH 7). Ozone reacts rapidly with all four moieties of ranitidine (k=1.5*10(5)-1.6*10(6)M(-1)s( 1) at pH 7) and its reaction with the tertiary amine or furan moiety leads to complete elimination of the NDMA-FP. Treatments of ranitidine-spiked real water samples have shown that ozonation can efficiently deactivate ranitidine in water and wastewater treatment, while chlorination can be efficient for water containing low concentration of ammonia. This result can be applied to the other structurally similar, potent NDMA precursors. PMID- 27381235 TI - Evolution in the Management of Pediatric and Adolescent Ovarian Torsion as a Result of Quality Improvement Measures. AB - STUDY OBJECTIVE: The aim of this study was to document the change in ovarian conservation rate after ovarian torsion as a result of continuous quality improvement (CQI) measures, and to determine factors that contribute to this outcome. DESIGN: A retrospective, uncontrolled before-and-after study. SETTING: An academic children's hospital. PARTICIPANTS: Female adolescents younger than 18 years with surgically confirmed ovarian torsion from April 1, 1988 to October 15, 2013; excluding cases from 2003 (intervention period). INTERVENTIONS: Implementation of CQI measures including educational programs, collaborative care pathways, and quality review with the goal of improving ovarian conservation. MAIN OUTCOME MEASURES: Demographic characteristics, details on presentation, investigations, consultation, surgical intervention, surgical findings, pathology, postoperative course, and follow-up imaging. RESULTS: One hundred thirty-nine patients met inclusion criteria (42 pre-CQI cohort and 97 post-CQI cohort). Mean ages were 9.96 and 10.33 years, respectively. Ovarian conservation rates were 47.6% compared with 85.6%, respectively (P < .001). The following factors differed between cohorts: fever (P = .003), ultrasound completed (P = .001), time from first health care provider visit to imaging (P = .025), time from specialist consultation to surgery (P = .002), surgical start time within 1 hour of booking (P < .001), and gynecologist present in operating room (P < .001). A log-binomial regression model showed that gynecology presence in the operating room (relative risk [RR], 2.043) was associated with untwisting. Increasing time from specialist consultation to surgery (RR, 0.986 per hour) was inversely associated with untwisting. Fever at presentation was also inversely associated with untwisting (RR, 0.666). CONCLUSION: The implementation of CQI measures was associated with a significant increase in ovarian conservation rate. PMID- 27381236 TI - Adolescent and Parent Willingness to Participate in Microbicide Safety Studies. AB - STUDY OBJECTIVE: To understand adolescents' and parents' willingness to participate (WTP) in a hypothetical phase I prevention study of sexually transmitted infections, discordance within adolescent-parent dyads, and expectations of each other during decision-making. DESIGN AND SETTING: Adolescent parent dyads were recruited to participate in a longitudinal study about research participation attitudes. PARTICIPANTS: Adolescents (14-17 years old) and their parents (n = 301 dyads) participated. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Individual interviews at baseline assessed WTP on a 6-level Likert scale. WTP was dichotomized (willing/unwilling) to assess discordance. RESULTS: WTP was reported by 60% (182 of 301) of adolescents and 52% (156 of 300) of parents. In bivariate analyses, older adolescent age, sexual experience, and less involvement of parents in research processes were associated with higher level of WTP for adolescents; only sexual experience remained in the multivariable analysis. For parents, older adolescent age, perceived adolescent sexual experience, and conversations about sexual health were significant; only conversations remained. Dyadic discordance (44%, 132 of 300) was more likely in dyads in which the parent reported previous research experience, and less likely when parents reported higher family expressiveness. Adolescents (83%, 248 of 299) and parents (88%, 263 of 300) thought that the other would have similar views, influence their decision (adolescents 66%, 199 of 300; parents 75%, 224 of 300), and listen (adolescents 90%, 270 of 300; parents 96%, 287 of 300). There were no relationships between these perceptions and discordance. CONCLUSION: Inclusion of adolescents in phase I clinical trials is necessary to ensure that new methods are safe, effective, and acceptable for them. Because these trials currently require parental consent, strategies that manage adolescent-parent discordance and support adolescent independence and parental guidance are critically needed. PMID- 27381237 TI - Does the Oral Contraceptive Pill Increase Plasma Intercellular Adhesion Molecule 1, Monocyte Chemoattractant Protein-1, and Tumor Necrosis Factor-alpha Levels in Women with Polycystic Ovary Syndrome: A Pilot Study. AB - STUDY OBJECTIVE: Polycystic ovary syndrome (PCOS), the most common endocrinopathy of women, is a state of chronic low-grade inflammation and is closely linked to type 2 diabetes mellitus and cardiovascular disease. Oral contraceptive pills (OCPs), is the usual first choice of treatment in women with PCOS. Because OCP use has been linked to the risk of venous thrombosis and there are limited data on the effect of OCP use on the inflammatory state of women with PCOS, our objective was to compare the levels of intercellular adhesion molecule (ICAM)-1, tumor necrosis factor (TNF)-alpha, and monocyte chemoattractant protein (MCP)-1 between drug-naive and OCP-treated women with PCOS. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Consequent to women diagnosed with PCOS on the basis of Rotterdam 2003 criteria, either treated with OCPs (ethinylestradiol 0.03 mg, levonogestrel-0.15 mg) for a period of 6 months (n = 50) or drug-naive (n = 51) were enrolled in this cross-sectional study. RESULTS: The mean ages of patients and control participants were comparable (21.99 +/- 4.78 vs 21.92 +/- 5.83 years; P = .947) as was body mass index (24.47 +/- 3.92 vs 23.66 +/- 3.43; P = .271). Clinical and androgen excess symptoms were significantly better in the OCP group compared with the drug-naive group (P = .01, P = .04). Total cholesterol and low-density lipoprotein cholesterol levels were significantly higher in the OCP group (P = .01). Plasma ICAM-1 levels, TNF alpha levels, and MCP-1 levels showed a higher trend in patients but reached statistical significance only in cases of ICAM-1 and TNF-alpha (P = .01). CONCLUSION: OCP treatment of 6 months increases plasma ICAM-1, MCP-1, and TNF alpha levels among women with PCOS, although OCPs significantly help in ameliorating features of hyperandrogenism and regularizing menstrual cycles. These cytokines correlate positively with many metabolic parameters including plasma glucose, lipids, and homeostatic model assessment-insulin resistance. Further investigation with well designed, randomized, longitudinal studies might help to ascertain the effect of OCPs on proinflammatory profiles among women with PCOS. PMID- 27381238 TI - Iridium(iii)-catalyzed regioselective direct arylation of sp(2) C-H bonds with diaryliodonium salts. AB - A regioselective direct arylation of arenes and olefins at the ortho position is reported. The key to the high selectivity is the appropriate choice of diaryliodonium salts as the arylating reagent in the presence of a cationic iridium(iii) catalyst. The coordination of the metal with an oxygen atom or a nitrogen atom and subsequent C-H activation allows for direct arylation with coupling partners. This reaction proceeds under mild reaction conditions and with a high tolerance of various functional groups including many halide functional groups. PMID- 27381239 TI - Erratum to: Complementary school garden, nutrition, water, sanitation and hygiene interventions to improve children's nutrition and health status in Burkina Faso and Nepal: a study protocol. PMID- 27381240 TI - Spotlights on our sister journals: Chem. Asian J. 13/2016. PMID- 27381242 TI - Cancer biology: The dark side of p21. PMID- 27381241 TI - Widespread detection of highly pathogenic H5 influenza viruses in wild birds from the Pacific Flyway of the United States. AB - A novel highly pathogenic avian influenza virus belonging to the H5 clade 2.3.4.4 variant viruses was detected in North America in late 2014. Motivated by the identification of these viruses in domestic poultry in Canada, an intensive study was initiated to conduct highly pathogenic avian influenza surveillance in wild birds in the Pacific Flyway of the United States. A total of 4,729 hunter harvested wild birds were sampled and highly pathogenic avian influenza virus was detected in 1.3% (n = 63). Three H5 clade 2.3.4.4 subtypes were isolated from wild birds, H5N2, H5N8, and H5N1, representing the wholly Eurasian lineage H5N8 and two novel reassortant viruses. Testing of 150 additional wild birds during avian morbidity and mortality investigations in Washington yielded 10 (6.7%) additional highly pathogenic avian influenza isolates (H5N8 = 3 and H5N2 = 7). The geographically widespread detection of these viruses in apparently healthy wild waterfowl suggest that the H5 clade 2.3.4.4 variant viruses may behave similarly in this taxonomic group whereby many waterfowl species are susceptible to infection but do not demonstrate obvious clinical disease. Despite these findings in wild waterfowl, mortality has been documented for some wild bird species and losses in US domestic poultry during the first half of 2015 were unprecedented. PMID- 27381243 TI - Applying CRISPR-Cas9 tools to identify and characterize transcriptional enhancers. AB - The development of the CRISPR-Cas9 system triggered a revolution in the field of genome engineering. Initially, the use of this system was focused on the study of protein-coding genes but, recently, a number of CRISPR-Cas9-based tools have been developed to study non-coding transcriptional regulatory elements. These technological advances offer unprecedented opportunities for elucidating the functions of enhancers in their endogenous context. Here, we discuss the application, current limitations and future development of CRISPR-Cas9 systems to identify and characterize enhancer elements in a high-throughput manner. PMID- 27381244 TI - Protein translocation: Channelling the route for ER misfolded proteins. PMID- 27381246 TI - Health Policy Repertoires and Toolboxes. PMID- 27381247 TI - Influenza nucleoprotein DNA vaccination by a skin targeted, dry coated, densely packed microprojection array (Nanopatch) induces potent antibody and CD8(+) T cell responses. AB - DNA vaccines have many advantages such as thermostability and the ease and rapidity of manufacture; for example, in an influenza pandemic situation where rapid production of vaccine is essential. However, immunogenicity of DNA vaccines was shown to be poor in humans unless large doses of DNA are used. If a highly efficacious DNA vaccine delivery system could be identified, then DNA vaccines have the potential to displace protein vaccines. In this study, we show in a C57BL/6 mouse model, that the Nanopatch, a microprojection array of high density (>21,000 projections/cm(2)), could be used to deliver influenza nucleoprotein DNA vaccine to skin, to generate enhanced antigen specific antibody and CD8(+) T cell responses compared to the conventional intramuscular (IM) delivery by the needle and syringe. Antigen specific antibody was measured using ELISA assays of mice vaccinated with a DNA plasmid containing the nucleoprotein gene of influenza type A/WSN/33 (H1N1). Antigen specific CD8(+) T cell responses were measured ex-vivo in splenocytes of mice using IFN-gamma ELISPOT assays. These results and our previous antibody and CD4(+) T cell results using the Nanopatch delivered HSV DNA vaccine indicate that the Nanopatch is an effective delivery system of general utility that could potentially be used in humans to increase the potency of the DNA vaccines. PMID- 27381248 TI - Advances in psoriasis physiopathology and treatments: Up to date of mechanistic insights and perspectives of novel therapies based on innovative skin drug delivery systems (ISDDS). AB - Psoriasis is a chronic inflammatory disease affecting mainly the skin but which can be complicated by psoriatic arthritis (PsA).This autoimmune skin disorder concerns 2-5% of the world population. To date, the physiopathology of psoriasis is not still completely elucidated but many researches are ongoing which have led for example to the discovery of the Th17/Th22 pathway. The conventional therapeutic approaches (local or systemic route) appeal to various classes of drugs with complex mechanisms of action and non-negligible side effects. Although there is no therapy capable to cure psoriasis, the current goal is to relieve symptoms as longer as possible with a good benefit/risk ratio. That is one of the principal limits of conventional antipsoriatic drugs. New formulations based on nanoencapsulation are a promising opportunity to answer to this limit by offering an optimization of the conventional antipsoriatic drug use (higher activity, lower side effects and frequency of application, etc.). Herein, we tried to put in perspective the mechanistic insights (histological and immunological views) proposed into scientific literature these last years in order to have a better comprehension of psoriasis physiopathology resulting in skin lesions and PsA. The therapeutic armamentarium and the different strategies in the management of psoriasis are discussed in greater details. To finish, the field of encapsulation in nanoparticles is broached in order to put forward recent advances in innovative skin drug delivery systems (ISDDSs) of antipsoriatic active agents for a better efficacy, safety and compliance. PMID- 27381245 TI - Mechanistic insights into selective autophagy pathways: lessons from yeast. AB - Autophagy has burgeoned rapidly as a field of study because of its evolutionary conservation, the diversity of intracellular cargoes degraded and recycled by this machinery, the mechanisms involved, as well as its physiological relevance to human health and disease. This self-eating process was initially viewed as a non-selective mechanism used by eukaryotic cells to degrade and recycle macromolecules in response to stress; we now know that various cellular constituents, as well as pathogens, can also undergo selective autophagy. In contrast to non-selective autophagy, selective autophagy pathways rely on a plethora of selective autophagy receptors (SARs) that recognize and direct intracellular protein aggregates, organelles and pathogens for specific degradation. Although SARs themselves are not highly conserved, their modes of action and the signalling cascades that activate and regulate them are. Recent yeast studies have provided novel mechanistic insights into selective autophagy pathways, revealing principles of how various cargoes can be marked and targeted for selective degradation. PMID- 27381250 TI - High-resolution community profiling of arbuscular mycorrhizal fungi. AB - Community analyses of arbuscular mycorrhizal fungi (AMF) using ribosomal small subunit (SSU) or internal transcribed spacer (ITS) DNA sequences often suffer from low resolution or coverage. We developed a novel sequencing based approach for a highly resolving and specific profiling of AMF communities. We took advantage of previously established AMF-specific PCR primers that amplify a c. 1.5-kb long fragment covering parts of SSU, ITS and parts of the large ribosomal subunit (LSU), and we sequenced the resulting amplicons with single molecule real time (SMRT) sequencing. The method was applicable to soil and root samples, detected all major AMF families and successfully discriminated closely related AMF species, which would not be discernible using SSU sequences. In inoculation tests we could trace the introduced AMF inoculum at the molecular level. One of the introduced strains almost replaced the local strain(s), revealing that AMF inoculation can have a profound impact on the native community. The methodology presented offers researchers a powerful new tool for AMF community analysis because it unifies improved specificity and enhanced resolution, whereas the drawback of medium sequencing throughput appears of lesser importance for low diversity groups such as AMF. PMID- 27381249 TI - The allergic march comprises the coexistence of related patterns of allergic disease not just the progressive development of one disease. AB - AIM: This study explored the development and comorbidity of allergic diseases by analysing the relationship between allergic manifestations in infancy and at the age of 8. METHODS: We included 5654 children born in Sweden in 2003 in a longitudinal study. Parents answered postal questionnaires when the children were six months and one, four-and-a-half and eight years of age. RESULTS: The response rate at eight years was 4051 (71.6%), and we analysed 3382 children with complete data. The number of manifestations in infancy increased the risk of allergic disease at eight years of age: 72% of children with one early manifestation were symptom free at 8, compared to 45% with two or more manifestations. Similar manifestations occurred in infancy and at the age of 8, for example recurrent wheeze increased the risk of doctor-diagnosed asthma by an adjusted odds ratio of 6.5. Eczema and food allergy independently increased the risk of all four allergic manifestations at eight years. CONCLUSION: Allergic disease at the age of 8 was related to the number of allergic manifestations in infancy. Manifestations were similar at both ages, suggesting an allergic march with the coexistence of disease patterns rather than the progressive development of one disease. PMID- 27381251 TI - Effectiveness of basic fibroblast growth factor for pediatric hand burns. AB - AIM OF THE STUDY: Pediatric hand deep dermal and deep burns may lead to serious hand deformity with functional impairment and result in an esthetically unfavorable outcome. Since there is no guideline regarding the use of growth factors for pediatric hand burns, we sought to investigate the effectiveness of an angiogenic and regenerative growth factor, basic fibroblast growth factor (bFGF). METHODS: Consecutive series of second degree or third degree palmer burns at less than 3 years of age seen from January 2010 to June 2014 were included for evaluation at 6 months post-wound healing. The bFGF treatment started from just after injury and continued up to 21 days. Each patient had their scars scored using the Vancouver Scar Scale (VSS) at 6 months after wound healing. RESULTS: There were 34 children with 49 acute palmar burns. The mean healing period was 13.5 +/- 4.3 days (7-44 days) and 43 wounds healed within 21 days. There was no need of additional surgery in the 43 wounds, healed within 21 days. In comparison to the wounds for which healing took more than 21 days, the wounds that healed within 21 days demonstrated significantly better pigmentation, pliability, and height according to the VSS (p < 0.05), as well as no scar contracture or hypertrophic scars. CONCLUSION: bFGF treatment was effective in cases that healed within 21 days, avoiding scar contractures and hypertrophic scars. Our methods using bFGF to complete wound healing are less invasive and produce better results in pediatric palmer burns. PMID- 27381252 TI - Large-area single-crystal graphene grown on a recrystallized Cu(111) surface by using a hole-pocket method. AB - We describe an efficient chemical vapor deposition (CVD) method for synthesizing graphene with a single crystal orientation on the whole surface of a copper (Cu) foil. We specifically synthesized graphene on the inner surface of a folded Cu foil, on which small holes were made for regulating the permeation and adsorption of the gases used for the synthesis. We compared the results of this method, which we call a "hole-pocket" method, with previously developed methods involving traditional synthesis on an open Cu foil and a Cu "pita-pocket". From these comparisons, we found the orientation of recrystallized Cu to depend on the shape of the Cu foil. Our hole-pocket method did not require treatment of the Cu surface with a complicated process to reduce the density of nucleation seeds in order to synthesize large hexagonal graphene grains, nor did it require the use of a single-crystalline substrate because methane passing through holes on the upper side of the hole-pocket slowly decomposed into carbon atoms and the control of the evaporation of Cu inside the foil pocket helped induce a transformation of the Cu domains to Cu(111). The current hole-pocket method resulted in domains that were both large, ranging from 2-5 mm in size, and oriented in the same manner. By extending the synthesis time, we were able to obtain continuous large area films of single-crystalline orientation on the whole surface with dimensions of several centimeters. PMID- 27381253 TI - Oxytocin enhances cognitive control of food craving in women. AB - In developed countries, obesity has become an epidemic resulting in enormous health care costs for society and serious medical complications for individuals. The homeostatic regulation of food intake is critically dependent on top-down control of reward-driven food craving. There is accumulating evidence from animal studies that the neuropeptide oxytocin (OXT) is involved in regulating hunger states and eating behavior, but whether OXT also contributes to cognitive control of food craving in humans is still unclear. We conducted a counter-balanced, double-blind, within-subject, pharmacological magnetic resonance imaging experiment involving 31 healthy women who received 24 IU of intranasal OXT or placebo and were scanned twice while they were exposed to pictures of palatable food. The participants were instructed either to imagine the immediate consumption or to cognitively control the urge to eat the food. Our results show a trend that OXT specifically reduced food craving in the cognitive control condition. On the neural level, these findings were paralleled by an increase of activity in the middle and superior frontal gyrus, precuneus, and cingulate cortex under OXT. Interestingly, the behavioral OXT effect correlated with the OXT-induced changes in the prefrontal cortex and precuneus. Collectively, the present study provides first evidence that OXT plays a key role in the cognitive regulation of food craving in women by strengthening activity in a broad neurocircuitry implicated in top-down control and self-referential processing. Hum Brain Mapp 37:4276-4285, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27381254 TI - Evaluation and reporting of quality of life outcomes in phase III chemotherapy trials for poor prognosis malignancies. AB - BACKGROUND: Quality of life (QoL) should be included in trials where treatment is expected to have a limited impact on long-term survival. We set out to determine whether phase III chemotherapy trials addressing solid malignancies with a poor prognosis include QoL as a study objective and to assess the extent to which these data have been published. METHODS: We performed a search of the National Institutes of Health clinical trial registry website to identify phase III chemotherapy trials for poor prognosis solid malignancies. The retrieved protocols were subsequently reviewed, to assess whether QoL was included as an outcome measure. Subsequently, a Medline, Embase and world-wide-web search was performed to identify any full text publication or conference abstract regarding the outcome of trials including QoL, which were then reviewed to determine whether and to what extend quality of life results were included. RESULTS: For the 201 included studies, we found that 57 % of trials did not include QoL as a study objective. Of the remaining trials, 50 % have not reported the QoL results in a full text publication, or presented these only as a single sentence statement. CONCLUSION: Evaluation and publication of QoL results of phase III chemotherapy trials for poor prognosis solid malignancies remains limited. This must be improved in order to provide patients suffering from these malignancies with adequate information regarding the benefits and risks of the treatment in terms of both prolongation and quality of life. PMID- 27381256 TI - Clinical experience with desflurane for paediatric anaesthesia outside the operating room. AB - BACKGROUND: Desflurane has been used in paediatric patients for several surgical indications. This article analyses the efficacy and safety of desflurane for diagnostic-therapeutic procedures in remote areas far from operating room in a group of selected patients with no known associated respiratory disease. MATERIAL AND METHODS: A retrospective analysis was performed on 2,072 general anaesthesia procedures stored in a computer database, in which desflurane was used in a Paediatric Pain Unit during the years 2013 and 2014. An analysis was also performed using the patient demographics, type of procedure, anaesthetic technique, type of airway management, patient cooperation, and incidence of anaesthetic complications. RESULTS: The study included 876 patients, with a mean age of 8.8 years. The main procedures were bone marrow aspirates (23%), lumbar punctures (20%), panendoscopies (15%), and colonoscopies (5%). Induction was intravenous with propofol (26%) or inhalation with sevoflurane in the remaining 74%. Maintenance consisted of remifentanil and desflurane at mean end tidal concentrations of 6.2+/-2.1%. The airway was managed through a nasal cannula or face mask in spontaneous ventilation. The effectiveness was 98%, and the incidence of side effects was 15%, which included agitation (6%), headache (4%), nausea-vomiting (3%), and laryngospasm (2%). CONCLUSION: The maintenance with desflurane (at concentrations close to the hypnotic-MAC in spontaneous ventilation) was effective, with a rapid recovery, and with a low incidence of adverse effects. PMID- 27381255 TI - Mutations in the G-domain of Ski7 cause specific dysfunction in non-stop decay. AB - Ski7 functions as a cofactor in both normal mRNA turnover and non-stop mRNA decay (NSD) mRNA surveillance in budding yeast. The N-terminal region of Ski7 (Ski7N) interacts with the ski-complex and the exosome. The C-terminal region of Ski7 (Ski7C) binds guanine nucleotides and shares overall sequence and structural homology with the proteins of the translational GTPase superfamily, especially the tRNA/tRNA-mimic carrier protein subfamilies such as EF1alpha, eRF3, and Hbs1. Previous reports showed that Ski7N polypeptide functions adequately in vivo, while Ski7C, if any, only slightly. Furthermore, Ski7C does not exhibit GTP hydrolysing activities under normal conditions. Therefore, the physiological and functional significance of the conserved Ski7C is unclear. Here, we report strong genetic evidence suggesting differential roles for Ski7N and Ski7C in normal and specific mRNA turnover pathways by creating/isolating mutations in both Ski7N and Ski7C conserved motifs using indicator yeast strains. We concluded that Ski7C participates in mRNA surveillance as a regulatory module competitively with the Hbs1/Dom34 complex. Our results provide insights into the molecular regulatory mechanisms underlying mRNA surveillance. PMID- 27381257 TI - Lactobacillus rhamnosus strain JB-1 reverses restraint stress-induced gut dysmotility. AB - BACKGROUND: Environmental stress affects the gut with dysmotility being a common consequence. Although a variety of microbes or molecules may prevent the dysmotility, none reverse the dysmotility. METHODS: We have used a 1 hour restraint stress mouse model to test for treatment effects of the neuroactive microbe, L. rhamnosus JB-1TM . Motility of fluid-filled ex vivo gut segments in a perfusion organ bath was recorded by video and migrating motor complexes measured using spatiotemporal maps of diameter changes. KEY RESULTS: Stress reduced jejunal and increased colonic propagating contractile cluster velocities and frequencies, while increasing contraction amplitudes for both. Luminal application of 10E8 cfu/mL JB-1 restored motor complex variables to unstressed levels within minutes of application. L. salivarius or Na.acetate had no treatment effects, while Na.butyrate partially reversed stress effects on colonic frequency and amplitude. Na.propionate reversed the stress effects for jejunum and colon except on jejunal amplitude. CONCLUSIONS & INFERENCES: Our findings demonstrate, for the first time, a potential for certain beneficial microbes as treatment of stress-induced intestinal dysmotility and that the mechanism for restoration of function occurs within the intestine via a rapid drug-like action on the enteric nervous system. PMID- 27381258 TI - The use of multiple pseudo-physiological solutions to simulate the degradation behavior of pure iron as a metallic resorbable implant: a surface characterization study. AB - Understanding the interactions of a pure iron surface with biological elements, such as ions and proteins in an aqueous medium, is essential for an accurate in vitro assessment of corrosion patterns. In fact, the synergy of chlorides, carbonates, phosphates and complex organic molecules present in the body environment is a key factor affecting both in vivo and in vitro degradation of materials, especially iron and its alloys. The aim of this work was the assessment of degradation patterns of pure iron in 5 commercial pseudo physiological solutions by a thorough study of degraded surface chemistry and morphology. It also provides a methodological basis to understand the short-term degradation mechanism of degradable iron depending on the surrounding physiological media. The standard static immersion corrosion test was modified to adapt the procedure to pseudo-physiological solutions. After a 14-day static immersion test, the surfaces of samples were investigated by scanning electron microscopy, stylus profilometry and atomic force microscopy techniques. The chemistry and phase composition of the degraded layers were evaluated, respectively, by X-ray photoelectron spectrometry and X-ray diffractometry. The morphology and composition of the degradation layers were found to be different for the test-solutions: for phosphate-rich solutions, the formation of an adherent passive layer was found; degradation mechanisms related to general corrosion were predominant for all the other solutions. In conclusion, the chemical composition of the used medium plays a fundamental role in the degradation pattern of pure iron, so that direct comparisons of solutions with different ion concentrations, as reported in the literature, need to be carefully assessed. PMID- 27381260 TI - Neurohumoral-renal interactions in blood pressure control. PMID- 27381261 TI - International Committee on Systematics of Prokaryotes Subcommittee on the taxonomy of Halobacteriaceae and subcommittee on the taxonomy of Halomonadaceae. Minutes of the joint open meeting, 23 May 2016, San Juan, Puerto Rico. PMID- 27381259 TI - Impaired neurodevelopment by the low complexity domain of CPEB4 reveals a convergent pathway with neurodegeneration. AB - CPEB4 is an RNA binding protein expressed in neuronal tissues including brain and spinal cord. CPEB4 has two domains: one that is structured for RNA binding and one that is unstructured and low complexity that has no known function. Unstructured low complexity domains (LCDs) in proteins are often found in RNA binding proteins and have been implicated in motor neuron degenerative diseases such as amyotrophic lateral sclerosis, indicating that these regions mediate normal RNA processing as well as pathological events. While CPEB4 null knockout mice are normal, animals expressing only the CPEB4 LCD are neonatal lethal with impaired mobility that display defects in neuronal development such as reduced motor axon branching and abnormal neuromuscular junction formation. Although full length CPEB4 is nearly exclusively cytoplasmic, the CPEB4 LCD forms nucleolar aggregates and CPEB4 LCD-expressing animals have altered ribosomal RNA biogenesis, ribosomal protein gene expression, and elevated levels of stress response genes such as the actin-bundling protein DRR1, which impedes neurite outgrowth. Some of these features share similarities with other LCD-related neurodegenerative disease. Most strikingly, DRR1 appears to be a common focus of several neurodevelopmental and neurodegenerative disorders. Our study reveals a possible molecular convergence between a neurodevelopmental defect and neurodegeneration mediated by LCDs. PMID- 27381262 TI - Defined enzyme cocktail from the anaerobic fungus Orpinomyces sp. strain C1A effectively releases sugars from pretreated corn stover and switchgrass. AB - The anaerobic fungus Orpinomyces strain C1A is capable of growth on various types of lignocellulosic substrates, and harbors an impressive reservoir of carbohydrate active enzymes (CAZymes). Using a minimum enzyme cocktail strategy, we constituted a four-component lignocellulolytic cocktail derived from highly transcribed C1A, and evaluated its efficacy against pretreated corn stover and switchgrass. Hydrolysis yields ranged between 65-77.4%, depending on the lignocellulosic substrate and pretreatment applied. Addition of a highly expressed anaerobic fungal swollenin improved hydrolysis yields by up to 7%. Compared to the commercial cocktail CTec2, these anaerobic fungal cocktails provided comparable or slightly lower hydrolysis yields. Further, the differences in efficacy between commercial and anaerobic cocktails were often only realized after extended (168 hr) incubations. Under certain conditions, the hydrolysis yields of the anaerobic fungal cocktail was slightly superior to that realized by CTec2. We attribute the observed high hydrolysis yields to the high specific activity and affinity of the individual enzymes of the cocktail, as well as the high level of synergy and multi-functionality observed in multiple components. Collectively, this effort provides a novel platform for constructing highly effective enzymes for biofuel production and represents the first lignocellulolytic enzyme cocktail created from anaerobic fungal enzymes. PMID- 27381263 TI - A Randomized Study of SheathLess vs Standard Guiding Catheters for Transradial Percutaneous Coronary Interventions. AB - BACKGROUND: The small diameter of radial arteries remains a major limitation of the transradial approach for percutaneous coronary intervention (PCI). Sheathless guiding catheters (GCs) might offer an advantage over standard GCs. METHODS: Between 2011 and 2013, we randomized 233 transradial PCIs performed in men with ostial or bifurcation lesions and in all women between standard GC (Medtronic Launcher; Minneapolis, MN) and the SheathLess Eaucath GC (Asahi Intecc, Aichi, Japan). RESULTS: Successful PCI using the transradial approach was not different between the groups (P = 0.74), however the rate of successful transradial PCI with the designated GC (ie, without crossover to the opposing GC) was superior in the SheathLess group compared with the standard GC group (96.5% vs 89.9%; P = 0.047). Safety end point (ie, absence of PCI complication, radial artery occlusion, perforation, pseudoaneurysm, and Early Discharge after Transradial Stenting of Coronary Arteries [EASY] hematoma grade >= 2) did not differ between the groups (60.5% in both groups). Mean PCI duration (45.1 minutes vs 45.9 minutes), fluoroscopy (20.1 minutes and 19.9 minutes), and cannulation times (3.6 minutes vs 3.7 minutes), contrast media volume (196 mL vs 187 mL) and conversion to transfemoral approach (1.8% vs 0.8%) were not different between the groups. Patients' subjective assessment revealed less arm pain during navigation of the SheathLess GC (1.9 +/- 1.9 vs 4.8 +/- 3.6; P < 0.001). Operators graded arm crossability as easier with the SheathLess GC (8.7 +/- 1.5 vs 5.1 +/- 3.5; P < 0.001). CONCLUSIONS: In selected coronary lesions requiring large-bore catheters in men and in all lesions in women, the SheathLess GC was superior to the standard GC for successful transradial PCI with the designated GC. The SheathLess GC was also associated with easier arm navigation and less patient discomfort. PMID- 27381264 TI - Valproic acid exposure decreases Cbp/p300 protein expression and histone acetyltransferase activity in P19 cells. AB - The teratogenicity of the antiepileptic drug valproic acid (VPA) is well established and its inhibition of histone deacetylases (HDAC) is proposed as an initiating factor. Recently, VPA-mediated HDAC inhibition was demonstrated to involve transcriptional downregulation of histone acetyltransferases (HATs), which was proposed to compensate for the increased acetylation resulting from HDAC inhibition. Cbp and p300 are HATs required for embryonic development and deficiencies in either are associated with congenital malformations and embryolethality. The objective of the present study was to characterize Cbp/p300 following VPA exposure in P19 cells. Consistent with previous studies, exposure to 5mM VPA over 24h induced a moderate decrease in Cbp/p300 mRNA, which preceded a strong decrease in total cellular protein mediated by ubiquitin-proteasome degradation. Nuclear Cbp/p300 protein was also decreased following VPA exposure, although to a lesser extent. Total cellular and nuclear p300 HAT activity was reduced proportionately to p300 protein levels, however while total cellular HAT activity also decreased, nuclear HAT activity was unaffected. Using the Cbp/p300 HAT inhibitor C646, we demonstrated that HAT inhibition similarly affected many of the same endpoints as VPA, including increased reactive oxygen species and caspase-3 cleavage, the latter of which could be attenuated by pre-treatment with the antioxidant catalase. C646 exposure also decreased NF-kappaB/p65 protein, which was not due to reduced mRNA and was not attenuated with catalase pre treatment. This study provides support for an adaptive HAT response following VPA exposure and suggests that reduced Cbp/p300 HAT activity could contribute to VPA mediated alterations. PMID- 27381265 TI - The 2015 Malcolm Ferguson-Smith Young Investigator Award. PMID- 27381266 TI - Risk factors for erosive and non-erosive gastroesophageal reflux disease and Barrett's esophagus in Nothern Sardinia. AB - OBJECTIVE: Gastroesophageal reflux disease (GERD) and esophageal adenocarcinoma have been increasing. We studied the relationship of conventional risk factors and Helicobacter pylori infection in patients with erosive and non-erosive GERD and Barrett's esophagus. MATERIALS AND METHODS: This was a retrospective study of dyspeptic patients undergoing upper endoscopy between 2002 and 2013. Following endoscopy, those with previously undiagnosed GERD were sub-grouped into non erosive GERD (NERD), erosive GERD (eGERD), or Barrett's esophagus. H. pylori status was confirmed by 2 positive tests. RESULTS: About 5156 patients were included, GERD was present in 65.6% including 1992 with NERD and 1392 with eGERD. About 1772 dyspeptic patients without symptoms of reflux and/or esophagitis served as controls. A hiatal hernia increased the risk of both eGERD and NERD. eGERD was more prevalent among the obese (OR =1.72, p < 0.001), men (OR =1.38, p < 0.001) and current smokers. Helicobacter pylori infection was significantly more common among those with NERD (OR =1.17 versus 1.01, p = 0.046). Logistic regression analysis for eGERD and NERD using age, gender, body mass index, H. pylori infection, hiatal hernia, and smoking showed that overweight and hiatal hernia were significant risk factors for eGERD, and female gender for NERD. Male gender, eGERD and age >50 years were the major risk factors for Barrett's esophagus. CONCLUSIONS: The epidemiology of eGERD and NERD suggests differences in pathogenesis, and prevention and treatment strategies should be separately examined in men and women. PMID- 27381267 TI - Botulinum neurotoxin treatment in children with cerebral palsy: validation of a needle placement protocol using passive muscle stretching and relaxing. AB - AIM: To validate a detailed intramuscular needle placement protocol using passive muscle stretching and relaxing for botulinum neurotoxin type A (BoNT-A) treatment in the lower extremity of children with spastic cerebral palsy (CP), with verification by electrical stimulation. METHOD: A prospective observational study was performed in 75 children with spastic CP who received regular BoNT-A treatment under general anaesthesia (52 males, 23 females; mean age 8y 9mo, SD 3y 7mo, range 4-18y; mean body mass index 16.2, SD 3.7, range 7.7-26.7). A total of 1084 intramuscular needle placements using passive muscle stretching and relaxing were verified by electrical stimulation. Primary outcome was the positive predictive value. RESULTS: Intramuscular needle placement in the muscles adductor brevis, adductor longus, gracilis, semimembranosus, semitendinosus, biceps femoris, rectus femoris, and lateral and medial heads of the gastrocnemius and soleus had a positive predictive value ranging from 85.7% to 100% (95% confidence interval ranging from 71.5-89.9% to 91.4-100%). INTERPRETATION: This validated detailed protocol for intramuscular needle placement using passive muscle stretching and relaxing for BoNT-A treatment in the lower extremity of children with spastic CP is reliable and has a high positive predictive value. PMID- 27381268 TI - Zirconia (ZrO2) Embedded in Carbon Nanowires via Electrospinning for Efficient Arsenic Removal from Water Combined with DFT Studies. AB - To use zirconia (ZrO2) as an efficient environmental adsorbent, it can be impregnated on a support to improve its physical properties and lower the overall cost. In this study, ZrO2 embedded in carbon nanowires (ZCNs) is fabricated via an electrospinning method to remove arsenic (As) from water. The maximum adsorption capacity values of As(III) and As(V) on the ZCNs are 28.61 and 106.57 mg/g, respectively, at 40 degrees C. These capacities are considerably higher than those of pure ZrO2 (2.56 and 3.65 mg/g for As(III) and As(V), respectively) created using the same procedure as for the ZCNs. Meanwhile, the adsorption behaviors of As(III) and As(V) on the ZCNs are endothermic and pH dependent and follow the Freundlich isotherm model and pseudo-first-order kinetic model. Both As(III) and As(V) are chemisorbed onto the ZCNs, which is confirmed by a partial density of state (PDOS) analysis and Dubinin-Radushkevich (D-R) model calculations. Furthermore, the ZCNs also possess the capability to enhance or catalyze the oxidation process of As(III) to As(V) using dissolved oxygen. This result is confirmed by a batch experiment, XPS analysis and Mulliken net charge analysis. Density functional theory (DFT) calculations indicate the different configurations of As(III) and As(V) complexes on the tetragonal ZrO2 (t ZrO2)(111) and monoclinic ZrO2 (m-ZrO2)(111) planes, respectively. The adsorption energy (Ead) of As(V) is higher than that of As(III) on both the t-ZrO2(111) and m-ZrO2 (111) planes (3.38 and 1.90 eV, respectively, for As(V) and 0.37 and 0.12 eV, respectively, for As(III)). PMID- 27381269 TI - Incorporation of Antiangiogenic Therapy Into the Non-Small-Cell Lung Cancer Paradigm. AB - Although molecular targeted agents have improved the treatment of lung cancer, their use has largely been restricted to limited subsets of the overall population that carry specific mutations. Angiogenesis, the formation of new blood vessels from existing networks, is an attractive, more general process for the development of targeted anticancer therapies, because it is critical for the growth of solid tumors, including non-small-cell lung cancer. Growing tissues require a vascular supply within a few millimeters. Therefore, solid tumors create a proangiogenic microenvironment to facilitate the development of new tumor-associated blood vessels, thus providing an adequate vascular supply for continued tumor growth. Antiangiogenic agents can specifically target the vascular endothelial growth factor (VEGF) signaling pathways, broadly inhibit multiple tyrosine kinases, or interfere with other angiogenic processes, such as disruption of existing tumor vasculature. The present report provides an overview of antiangiogenic therapy for non-small-cell lung cancer, including both currently approved antiangiogenic therapies (bevacizumab [anti-VEGF] and ramucirumab [anti-VEGF receptor 2] monoclonal antibodies), and a variety of promising novel agents in development. Although recent data have demonstrated promising efficacy for some novel agents, the overall development of antiangiogenic therapy has been hampered by redundancy in signaling pathways and the highly heterogeneous nature of tumors. An improved understanding of the molecular basis of angiogenesis will guide the development of new antiangiogenic therapies and the identification of biomarkers to predict which patients with lung cancer are most likely to benefit from antiangiogenic therapy. PMID- 27381271 TI - Atom and Bond Fukui Functions and Matrices: A Hirshfeld-I Atoms-in-Molecule Approach. AB - The Fukui function is often used in its atom-condensed form by isolating it from the molecular Fukui function using a chosen weight function for the atom in the molecule. Recently, Fukui functions and matrices for both atoms and bonds separately were introduced for semiempirical and ab initio levels of theory using Huckel and Mulliken atoms-in-molecule models. In this work, a double partitioning method of the Fukui matrix is proposed within the Hirshfeld-I atoms-in-molecule framework. Diagonalizing the resulting atomic and bond matrices gives eigenvalues and eigenvectors (Fukui orbitals) describing the reactivity of atoms and bonds. The Fukui function is the diagonal element of the Fukui matrix and may be resolved in atom and bond contributions. The extra information contained in the atom and bond resolution of the Fukui matrices and functions is highlighted. The effect of the choice of weight function arising from the Hirshfeld-I approach to obtain atom- and bond-condensed Fukui functions is studied. A comparison of the results with those generated by using the Mulliken atoms-in-molecule approach shows low correlation between the two partitioning schemes. PMID- 27381270 TI - EGFR Testing in Advanced Non-Small-Cell Lung Cancer, A Mini-Review. AB - Expert consensus guidelines have defined minimum requirements for routine testing and identification of classical epidermal growth factor (EGFR) mutations (ie, exon 19 deletions and exon 21 L858R substitution) and anaplastic lymphoma kinase (ALK) rearrangements in advanced non-small-cell lung cancers of adenocarcinoma histology, with the intent of permitting use of these predictive biomarkers to select patients who will derive maximal benefit from approved oral tyrosine kinase inhibitors (TKIs) directed against EGFR and ALK, respectively. However, the practice of precision medicine is incumbent upon optimal tumor sampling, accurate tumor testing, and informed application of results to patient care. We report on a brief review of EGFR testing methodologies (Sanger sequencing, allele specific polymerase chain reaction, and targeted next-generation sequencing) to identify classical and other (ie, exon 18 G719X, exon 19 insertions, exon 20 insertions, exon 21 L861Q) EGFR mutations; practical considerations (type of tissue/biopsies with different success rates of DNA isolation, and timeliness of result-reporting to facilitate therapeutic decision-making); role of rebiopsy (to identify mechanisms of acquired resistance to first- and second-generation EGFR TKIs, most importantly EGFR-T790M); and clinical vignettes highlighting the nuances of testing in day-to-day practice. PMID- 27381272 TI - RpoS-dependent sRNA RgsA regulates Fis and AcpP in Pseudomonas aeruginosa. AB - RgsA is a phylogenetically conserved small regulatory RNA (sRNA) in Pseudomonas species. This sRNA has been shown to be directly controlled by the major stationary phase and stress sigma factor sigmaS (RpoS), and also indirectly regulated by the GacS/GacA two-component system. However, the role and the regulatory targets of this sRNA remain unclear. Here, two direct regulatory targets of RgsA, the mRNAs coding for the global transcriptional regulator Fis and the acyl carrier protein AcpP, were identified in P. aeruginosa. RgsA downregulates the synthesis of Fis and AcpP by base-pairing, and this regulation requires the RNA chaperone protein Hfq. Alignment of RgsA homologs in Pseudomonas revealed a conserved core region, which is strictly required for RgsA target recognition. Specifically, RgsA inhibits fis expression via an 11 + 11 bp RNA duplex, whereas this interaction region is not sufficient for repression and the 35 nt downstream region is also required. Interestingly, two functional start codons initiate fis mRNA translation and both are repressed by RgsA. Furthermore, deletion of rgsA significantly increased swarming motility in P. aeruginosa. Together, this study suggests a novel regulatory role of sRNA in which the versatile transcriptional regulator Fis and the stress regulator RpoS are connected by RgsA. PMID- 27381273 TI - Studies in organic and physical photochemistry - an interdisciplinary approach. AB - Traditionally, organic photochemistry when applied to synthesis strongly interacts with physical chemistry. The aim of this review is to illustrate this very fruitful interdisciplinary approach and cooperation. A profound understanding of the photochemical reactivity and reaction mechanisms is particularly helpful for optimization and application of these reactions. Some typical reactions and particular aspects are reported such as the Norrish-Type II reaction and the Yang cyclization and related transformations, the [2 + 2] photocycloadditions, particularly the Paterno-Buchi reaction, photochemical electron transfer induced transformations, different kinds of catalytic reactions such as photoredox catalysis for organic synthesis and photooxygenation are discussed. Particular aspects such as the structure and reactivity of aryl cations, photochemical reactions in the crystalline state, chiral memory, different mechanisms of hydrogen transfer in photochemical reactions or fundamental aspects of stereoselectivity are discussed. Photochemical reactions are also investigated in the context of chemical engineering. Particularly, continuous flow reactors are of interest. Novel reactor systems are developed and modeling of photochemical transformations and different reactors play a key role in such studies. This research domain builds a bridge between fundamental studies of organic photochemical reactions and their industrial application. PMID- 27381274 TI - Action potential broadening in a presynaptic channelopathy. AB - Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca(2+) influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction. PMID- 27381275 TI - Efficacy and safety of switching from sitagliptin to liraglutide in subjects with type 2 diabetes (LIRA-SWITCH): a randomized, double-blind, double-dummy, active controlled 26-week trial. AB - AIMS: To confirm superiority on glycaemic control by switching from sitagliptin to liraglutide 1.8 mg/d versus continued sitagliptin. MATERIALS AND METHODS: A randomized, multicentre, double-blind, double-dummy, active-controlled trial across 86 office- or hospital-based sites in North America, Europe and Asia. Subjects with type 2 diabetes who had inadequate glycaemic control (glycated haemoglobin [HbA1c] 7.5-9.5% on sitagliptin (100 mg/d) and metformin (>=1500 mg daily) for >=90 days were randomized to either switch to liraglutide (n = 203) or continue sitagliptin (n = 204), both with metformin. The primary endpoint was change in HbA1c from baseline to week 26. Change in body weight was a confirmatory secondary endpoint. RESULTS: Greater reduction in mean HbA1c was achieved with liraglutide than with continued sitagliptin [-1.14% vs. -0.54%; estimated mean treatment difference (ETD): -0.61% (95% CI -0.82 to -0.40; p < 0.0001)], confirming superiority of switching to liraglutide. Body weight was reduced more with liraglutide [-3.31 kg vs. -1.64 kg; ETD: -1.67 kg (95% CI -2.34 to -0.99; p < 0.0001)]. Nausea was more common with liraglutide [44 subjects (21.8%)] than with continued sitagliptin [16 (7.8%)]. Three subjects (1.5%) taking sitagliptin reported a confirmed hypoglycaemic episode. CONCLUSIONS: Subjects insufficiently controlled with sitagliptin who switch to liraglutide can obtain clinically relevant reductions in glycaemia and body weight, without compromising safety. A switch from sitagliptin to liraglutide provides an option for improved management of type 2 diabetes while still allowing patients to remain on dual therapy. PMID- 27381276 TI - Multicomponent Combinatorial Polymerization via the Biginelli Reaction. AB - A multicomponent combinatorial polymerization method has been exploited as a new intersection between combinatorial chemistry, polymer chemistry, and organic chemistry. The tricomponent Biginelli reaction has been employed as a model multicomponent reaction (MCR) to efficiently prepare a library of polycondensates with continuously changed chain structure but different physical properties. The naturally increased reaction modules (monomers) directly doubled the number of polymers in the library, effectively improving the efficiency of polymer preparation. The glass transition temperatures (Tg) of those homologous polymers have been mapped for the first time to predict the Tg values of absent polymer homologues with good to excellent accuracy. Meanwhile, the Tg maps have also been used to reveal the regular change in Tg according to the polymer structure (linking group, monomer chain length, etc.), initially suggesting the academic significance of the multicomponent combinatorial polymerization system. We believe that the current research paves a straightforward way to synthesize new libraries of polymers via MCRs and might prompt the broader study of MCRs in interdisciplinary fields. PMID- 27381277 TI - Epigenetic determinants of cardiovascular gene expression: vascular endothelium. AB - The modern landscape of gene regulation involves interacting factors that ultimately lead to gene activation or repression. Epigenetic mechanisms provide a perspective of cellular phenotype as dynamically regulated and responsive to input. This perspective is supported by the generation of induced pluripotent stem cells from fully differentiated cell types. In vascular endothelial cells, evidence suggests that epigenetic mechanisms play a major role in the expression of endothelial cell-specific genes such as the endothelial nitric oxide synthase (NOS3/eNOS). These mechanisms are also important for eNOS expression in response to environmental stimuli such as hypoxia and shear stress. A newer paradigm in epigenetics, long noncoding RNAs offer a link between genetic variation, epigenetic regulation and disease. While the understanding of epigenetic mechanisms is early in its course, it is becoming clear that approaches to understanding the interaction of these factors and their inputs will be necessary to improve outcomes in cardiovascular disease. PMID- 27381278 TI - Analysis of Cell Size in the Gastrula of Ten Frog Species Reveals a Correlation of Egg with Cell Sizes, and a Conserved Pattern of Small Cells in the Marginal Zone. AB - We investigated the relationship between egg and cell sizes in the early gastrula of ten species of frogs with eggs of 1,100-3,500 MUm diameters. We asked whether differences in cell size of the vegetal region, blastocoel roof, and marginal zone of the early gastrula were associated with egg size. Alternatively, we proposed that cell size differences may associate with gastrulation characteristics. The analyzed species were as follows: Xenopus laevis, Engystomops randi, Engystomops coloradorum, Espadarana callistomma, Epipedobates machalilla, Epipedobates anthonyi, Epipedobates tricolor, Dendrobates auratus, Gastrotheca riobambae, and Eleutherodactylus coqui. A positive correlation between egg and cell size was detected in the three regions of the gastrula. The correlation was strong in the vegetal region and blastocoel roof, and weak in the marginal zone. Large eggs allowed the evolution of frog terrestrial reproductive modes by storing nourishment for the developing embryos. Large cells, laden with yolk, occur in the vegetal region. However, small cell size characterized the marginal zone and blastocoel roof. We proposed that small cells of the marginal zone are required for involution and blastopore formation. The evolution pressure toward small cells in the marginal zone contributed to maintain the blastopore as a universal feature of frog gastrulation in eggs of different sizes and gastrulation modes. Our comparative analysis revealed two fundamental and conserved properties of the frog early gastrula, the correlation of egg with cell sizes, and the general small size of cells in the marginal zone. PMID- 27381279 TI - The WHO Global Code: increasing relevance and effectiveness. PMID- 27381280 TI - Bioactive and biocompatible copper containing glass-ceramics with remarkable antibacterial properties and high cell viability designed for future in vivo trials. AB - In the present study our interest is focused on finding the efficiency of 60SiO2.(32 - x)CaO.8P2O5.xCuO (mol%) glass-ceramics, with 0 <= x <= 4 mol%, in terms of bioactivity, biocompatibility, antibacterial properties and cell viability in order to determine the most appropriate composition for their further use in in vivo trials. The sol-gel synthesized samples show a preponderantly amorphous structure with a few crystallization centers associated with the formation of an apatite and calcium carbonate crystalline phases. The Fourier Transform Infrared (FT-IR) spectra revealed slightly modified absorption bands due to the addition of copper oxide, while the information derived from the measurements performed by transmission electron microscopy, UV-vis and electron paramagnetic resonance spectroscopy showed the presence of ions and metallic copper species. X-Ray photoelectron spectroscopic analysis indicated the presence of copper metallic species, in a reduced amount, only on the sample surface with the highest Cu content. Regarding in vitro assessment of bioactivity, the results obtained by X-ray diffraction, FT-IR spectroscopy and scanning electron microscopy, demonstrated the formation of a calcium phosphate layer on all investigated sample surfaces. The inhibitory effect of the investigated samples was more significant on the Pseudomonas aeruginosa than the Staphylococcus aureus strain, the sample with the lowest concentration of copper oxide (0.5 mol%) being also the most efficient in both bacterial cultures. This sample also exhibits a very good bactericidal activity, for the other samples it was necessary to use a higher quantity to inhibit and kill the bacterial species. The secondary structure of adsorbed albumin presents few minor changes, indicating the biocompatibility of the glass-ceramics. The cell viability assay shows a good proliferation rate on samples with 0.5 and 1.5 mol% CuO, although all glass ceramic samples exhibited a good in vivo tolerance. PMID- 27381281 TI - Fully integrated multi-optoelectronic synthesizer for THz pumping source in wireless communications with rich backup redundancy and wide tuning range. AB - We report a monolithic photonic integrated circuit (PIC) for THz communication applications. The PIC generates up to 4 optical frequency lines which can be mixed in a separate device to generate THz radiation, and each of the optical lines can be modulated individually to encode data. Physically, the PIC comprises an array of wavelength tunable distributed feedback lasers each with its own electro-absorption modulator. The lasers are designed with a long cavity to operate with a narrow linewidth, typically <4 MHz. The light from the lasers is coupled via an multimode interference (MMI) coupler into a semiconductor optical amplifier (SOA). By appropriate selection and biasing of pairs of lasers, the optical beat signal can be tuned continuously over the range from 0.254 THz to 2.723 THz. The EAM of each channel enables signal leveling balanced between the lasers and realizing data encoding, currently at data rates up to 6.5 Gb/s. The PIC is fabricated using regrowth-free techniques, making it economic for volume applications, such for use in data centers. The PIC also has a degree of redundancy, making it suitable for applications, such as inter-satellite communications, where high reliability is mandatory. PMID- 27381282 TI - Enhancement of the coercivity in Co-Ni layered double hydroxides by increasing basal spacing. AB - The magnetic properties of layered double hydroxides (LDH) containing transition metal ions can still develop, compared with layered metal hydroxide salts which exhibit structure-dependent magnetism. In this article, we report the preparation of a hybrid magnet composed of Co-Ni LDH and n-alkylsulfonate anions (Co-Ni-CnSO3 LDH). As Co-Ni LDH is anion-exchangeable, we can systematically control the interlayer spacing by intercalating n-alkylsulfonates with different carbon numbers. The magnetic properties were examined with temperature- and field dependent magnetization measurements. As a result, we have revealed that the coercive field depends on the basal spacing. It is suggested that increasing the basal spacing varies the competition between the in-plane superexchange interactions and long-range out-of-plane dipolar interactions. Moreover, a jump in the coercive field at around 20 A of the basal spacing is assumed to be the modification of the magnetic ordering in Co-Ni-CnSO3 LDH. PMID- 27381283 TI - A behavioural approach in the development of work-related interventions for cancer survivors: an exploratory review. AB - The application of behavioural change models and theories has not been studied, and behavioural determinants have not been considered, in the context of cancer and work. The aim of this study is to assess the relevance of a behavioural approach in the development of work-related interventions for cancer survivors. Two search strategies were conducted to identify studies on (1) lifestyle interventions (exercise, smoking, alcohol intake and diet), based on behavioural models and theories, in cancer survivors; (2) behavioural determinants regarding work. Medline, Embase, PsycInfo, CINAHL and the Cochrane Controlled Trial Register were searched (2000-2015). Studies were assessed on their eligibility, and findings were listed and categorised. Thirty-four studies exploring lifestyle interventions in cancer survivors were retrieved. The behavioural change models and theories most regularly used were the Transtheoretical Model and Social Cognitive Theory. Furthermore, 26 studies on the role of behavioural determinants regarding work were found. The most frequently considered determinants were self efficacy, social norms, workers' expectations towards work or recovery, attitude, motivation and meaning of work. The results indicate the significance of behavioural change models and theories and of behavioural determinants in related research areas, which encourages a behavioural approach in the development of work-related interventions for cancer survivors. PMID- 27381284 TI - Phase diagram of quantum critical system via local convertibility of ground state. AB - We investigate the relationship between two kinds of ground-state local convertibility and quantum phase transitions in XY model. The local operations and classical communications (LOCC) convertibility is examined by the majorization relations and the entanglement-assisted local operations and classical communications (ELOCC) via Renyi entropy interception. In the phase diagram of XY model, LOCC convertibility and ELOCC convertibility of ground states are presented and compared. It is shown that different phases in the phase diagram of XY model can have different LOCC or ELOCC convertibility, which can be used to detect the quantum phase transition. This study will enlighten extensive studies of quantum phase transitions from the perspective of local convertibility, e.g., finite-temperature phase transitions and other quantum many body models. PMID- 27381285 TI - Successful obstetric and hematologic outcome of aplastic anemia in a pregnant Jehovah's Witness. PMID- 27381286 TI - Dose reduction of recombinant human tumor necrosis factor inhibitors (etanercept) can be effective in ankylosing spondylitis patients with synovitis of the hip in a Chinese population. AB - Ankylosing spondylitis (AS) is an immune-mediated inflammatory arthritis and enthesitis involving the spine and peripheral joints. In recent years, specific antagonist of tumor necrosis factor (anti-TNFalpha, etanercept) 50 mg weekly therapy has rapidly gained popularity for the treatment of AS. However, the dose of etanercept has not been determined in Asian, particularly Chinese populations. The purpose of the study was to evaluate the efficacy and safety of dose reduction of etanercept (50 mg/week in 4 weeks followed by 25 mg/week in 8 weeks) in the treatment of AS with synovitis of the hip, as against the conventional dose (50 mg/week in 12 weeks) in a Chinese population. Forty-three Chinese AS patients with synovitis of the hip were involved in this study. Seventeen of them were randomized to receive conventional dose of etanercept treatment and 26 were given a dose reduction regimen for 12 weeks. The primary efficacy endpoint was disease activity of response for AS at week 12, including Bath AS Disease Activity Index (BASDAI), the serum erythrocyte sediment rate (ESR), C-reactive protein (CRP), and assessment of synovitis of the hip by ultrasonography. At 12 weeks, all of the patients had responses to some extent and the efficacy variables improved significantly over time, but not between treatment groups. Nine patients experienced at least one adverse event (generally, infections and injection site reactions), most of them mild or moderate. In sum, the dose reduction of etanercept regimen in the 12-week AS treatment was confirmed as a safe and effective therapy as the conventional dose was given. PMID- 27381287 TI - Conformational Heterogeneity of Bax Helix 9 Dimer for Apoptotic Pore Formation. AB - Helix alpha9 of Bax protein can dimerize in the mitochondrial outer membrane (MOM) and lead to apoptotic pores. However, it remains unclear how different conformations of the dimer contribute to the pore formation on the molecular level. Thus we have investigated various conformational states of the alpha9 dimer in a MOM model - using computer simulations supplemented with site-specific mutagenesis and crosslinking of the alpha9 helices. Our data not only confirmed the critical membrane environment for the alpha9 stability and dimerization, but also revealed the distinct lipid-binding preference of the dimer in different conformational states. In our proposed pathway, a crucial iso-parallel dimer that mediates the conformational transition was discovered computationally and validated experimentally. The corroborating evidence from simulations and experiments suggests that, helix alpha9 assists Bax activation via the dimer heterogeneity and interactions with specific MOM lipids, which eventually facilitate proteolipidic pore formation in apoptosis regulation. PMID- 27381288 TI - Shutdown of HIV-1 Transcription in T Cells by Nullbasic, a Mutant Tat Protein. AB - Nullbasic is a derivative of the HIV-1 transactivator of transcription (Tat) protein that strongly inhibits HIV-1 replication in lymphocytes. Here we show that lentiviral vectors that constitutively express a Nullbasic-ZsGreen1 (NB ZSG1) fusion protein by the eEF1alpha promoter led to robust long-term inhibition of HIV-1 replication in Jurkat cells. Although Jurkat-NB-ZSG1 cells were infected by HIV-1, no virus production could be detected and addition of phorbol ester 12 myristate 13-acetate (PMA) and JQ1 had no effect, while suberanilohydroxamic acid (SAHA) modestly stimulated virus production but at levels 300-fold lower than those seen in HIV-1-infected Jurkat-ZSG1 cells. Virus replication was not recovered by coculture of HIV-1-infected Jurkat-NB-ZSG1 cells with uninfected Jurkat cells. Latently infected Jurkat latent 6.3 and ACH2 cells treated with latency-reversing agents produced measurable viral capsid (CA), but little or none was made when they expressed NB-ZSG1. When Jurkat cells chronically infected with HIV-1 were transduced with lentiviral virus-like particles conveying NB ZSG1, a >3-log reduction in CA production was observed. Addition of PMA increased virus CA production but at levels 500-fold lower than those seen in nontransduced Jurkat cells. Transcriptome sequencing analysis confirmed that HIV-1 mRNA was strongly inhibited by NB-ZSG1 but indicated that full-length viral mRNA was made. Analysis of HIV-1-infected Jurkat cells expressing NB-ZSG1 by chromatin immunoprecipitation assays indicated that recruitment of RNA polymerase II (RNAPII) and histone 3 lysine 9 acetylation were inhibited. The reduction of HIV 1 promoter-associated RNAPII and epigenetic changes in viral nucleosomes indicate that Nullbasic can inhibit HIV-1 replication by enforcing viral silencing in cells. IMPORTANCE: HIV-1 infection is effectively controlled by antiviral therapy that inhibits virus replication and reduces measurable viral loads in patients below detectable levels. However, therapy interruption leads to viral rebound due to latently infected cells that serve as a source of continued viral infection. Interest in strategies leading to a functional cure of HIV infection by permanent viral suppression, which may be achievable, is growing. Here we show that a mutant form of the HIV-1 Tat protein, referred to as Nullbasic, can inhibit HIV-1 transcription in infected Jurkat T cell to undetectable levels. Analysis shows that Nullbasic alters the epigenetic state of the HIV-1 long terminal repeat promoter, inhibiting its association with RNA polymerase II. This study indicates that key cellular proteins and pathways targeted here can silence HIV-1 transcription. Further elucidation could lead to functional-cure strategies by suppression of HIV transcription, which may be achievable by a pharmacological method. PMID- 27381289 TI - Ehrlichia chaffeensis TRP120 Activates Canonical Notch Signaling To Downregulate TLR2/4 Expression and Promote Intracellular Survival. AB - Ehrlichia chaffeensis preferentially targets mononuclear phagocytes and survives through a strategy of subverting innate immune defenses, but the mechanisms are unknown. We have shown E. chaffeensis type 1 secreted tandem repeat protein (TRP) effectors are involved in diverse molecular pathogen-host interactions, such as the TRP120 interaction with the Notch receptor-cleaving metalloprotease ADAM17. In the present study, we demonstrate E. chaffeensis, via the TRP120 effector, activates the canonical Notch signaling pathway to promote intracellular survival. We found that nuclear translocation of the transcriptionally active Notch intracellular domain (NICD) occurs in response to E. chaffeensis or recombinant TRP120, resulting in upregulation of Notch signaling pathway components and target genes notch1, adam17, hes, and hey Significant differences in canonical Notch signaling gene expression levels (>40%) were observed during early and late stages of infection, indicating activation of the Notch pathway. We linked Notch pathway activation specifically to the TRP120 effector, which directly interacts with the Notch metalloprotease ADAM17. Using pharmacological inhibitors and small interfering RNAs (siRNAs) against gamma-secretase enzyme, Notch transcription factor complex, Notch1, and ADAM17, we demonstrated that Notch signaling is required for ehrlichial survival. We studied the downstream effects and found that E. chaffeensis TRP120-mediated activation of the Notch pathway causes inhibition of the extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) pathways required for PU.1 and subsequent Toll-like receptor 2/4 (TLR2/4) expression. This investigation reveals a novel mechanism whereby E. chaffeensis exploits the Notch pathway to evade the host innate immune response for intracellular survival. IMPORTANCE: E. chaffeensis is an obligately intracellular bacterium and the etiologic agent of human monocytotropic ehrlichiosis (HME), an emerging life threatening tick-borne zoonosis. Mechanisms by which E. chaffeensis establishes intracellular infection and avoids innate host defenses are not understood, but functionally relevant host-pathogen interactions with type 1 secreted TRP effectors are essential for the ehrlichial cellular reprogramming strategy. This study provides further insight into the molecular strategies used by obligately intracellular pathogens such as E. chaffeensis, which have small genomes and a limited number of effector proteins and exploit evolutionarily conserved host cell programs such as Notch signaling to promote infection and intracellular survival. PMID- 27381290 TI - Mutations in the Plasmodium falciparum Cyclic Amine Resistance Locus (PfCARL) Confer Multidrug Resistance. AB - Mutations in the Plasmodium falciparum cyclic amine resistance locus (PfCARL) are associated with parasite resistance to the imidazolopiperazines, a potent class of novel antimalarial compounds that display both prophylactic and transmission blocking activity, in addition to activity against blood-stage parasites. Here, we show that pfcarl encodes a protein, with a predicted molecular weight of 153 kDa, that localizes to the cis-Golgi apparatus of the parasite in both asexual and sexual blood stages. Utilizing clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene introduction of 5 variants (L830V, S1076N/I, V1103L, and I1139K), we demonstrate that mutations in pfcarl are sufficient to generate resistance against the imidazolopiperazines in both asexual and sexual blood-stage parasites. We further determined that the mutant PfCARL protein confers resistance to several structurally unrelated compounds. These data suggest that PfCARL modulates the levels of small-molecule inhibitors that affect Golgi-related processes, such as protein sorting or membrane trafficking, and is therefore an important mechanism of resistance in malaria parasites. IMPORTANCE: Several previous in vitro evolution studies have implicated the Plasmodium falciparum cyclic amine resistance locus (PfCARL) as a potential target of imidazolopiperazines, potent antimalarial compounds with broad activity against different parasite life cycle stages. Given that the imidazolopiperazines are currently being tested in clinical trials, understanding their mechanism of resistance and the cellular processes involved will allow more effective clinical usage. PMID- 27381291 TI - How to Measure Export via Bacterial Multidrug Resistance Efflux Pumps. AB - Bacterial multidrug resistance (MDR) efflux pumps are an important mechanism of antibiotic resistance and are required for many pathogens to cause infection. They are also being harnessed to improve microbial biotechnological processes, including biofuel production. Therefore, scientists of many specialties must be able to accurately measure efflux activity. However, myriad methodologies have been described and the most appropriate method is not always clear. Within the scientific literature, many methods are misused or data arising are misinterpreted. The methods for measuring efflux activity can be split into two groups, (i) those that directly measure efflux and (ii) those that measure the intracellular accumulation of a substrate, which is then used to infer efflux activity. Here, we review the methods for measuring efflux and explore the most recent advances in this field, including single-cell or cell-free technologies and mass spectrometry, that are being used to provide more detailed information about efflux pump activity. PMID- 27381295 TI - Experimental and theoretical investigations of non-Newtonian electro-osmotic driven flow in rectangular microchannels. AB - With the development of microfluidics, electro-osmotic (EO) driven flow has gained intense research interest as a result of its unique flow profile and the corresponding benefits in its application in the transportation of sensitive samples. Sensitive samples, such as DNA, are incapable of enduring strong flow shear induced by conventional hydrodynamic driven methods. EO driven flow is thus a niche area. However, even though there are a few research studies focusing on bio-fluidic samples related to EO driven flow, the majority of them are merely theoretical modeling without solid evidence from experiments due to the inherent complex rheological behavior of the bio-fluids. Challenges occur when the EO driven mechanism meets with complex rheology; vital questions such as can the zeta potential still be assumed to be constant when dealing with fluids with complex rheology? and "Does the shear thinning effect enhance electro-osmotic driven flow?" need to be answered. We conducted experiments using current monitoring and microscopy fluorescence methods, and developed a theoretical model by coupling a generalized Smoluchowski approach with the power-law constitutive model. We calculated the zeta potential and compared the experimental results with modeling to answer the questions. The results show a reduction of zeta potential in the presence of PEO aqueous solutions. A constant zeta potential is also indicated by varying the PEO concentration and the electric field strength.The shear thinning effect is also addressed via experimental data and theoretical calculations. The results show a promising enhancement of the EO driven velocity due to the shear thinning effect. PMID- 27381294 TI - After All, Only Millions? AB - An update on the census of species of Archaea and Bacteria published recently in mBio (P. D. Schloss, R. A. Girard, T. Martin, J. Edwards, and J. C. Thrash, mBio 7:e00201-16, 2016, http://dx.doi.org/10.1128/mBio.00201-16) showed again that, despite ever-increasing sequencing efforts, the PCR-based retrieval of 16S rRNA genes is approaching saturation. On average, 95% of the genes analyzed today are identical to those present in public databases, with rarefaction analysis indicating that about one-third of the bacterial and archaeal diversity has already been covered. Therefore, despite estimates of up to 10(12) microbial species, the option should be considered that the census of Archaea and Bacteria on planet Earth might yield only millions of species after all. PMID- 27381292 TI - JC Polyomavirus Infection of Primary Human Renal Epithelial Cells Is Controlled by a Type I IFN-Induced Response. AB - The JC and BK human polyomaviruses (JCPyV and BKPyV, respectively) establish lifelong persistent infections in the kidney. In immunosuppressed individuals, JCPyV causes progressive multifocal leukoencephalopathy (PML), a fatal neurodegenerative disease, and BKPyV causes polyomavirus-associated nephropathy (PVN). In this study, we compared JCPyV and BKPyV infections in primary human renal proximal tubule epithelial (HRPTE) cells. JCPyV established a persistent infection, but BKPyV killed the cells in 15 days. To identify the cellular factors responsible for controlling JCPyV infection and promoting viral persistence, we profiled the transcriptomes of JCPyV- and BKPyV-infected cells at several time points postinfection. We found that infection with both viruses induced interferon production but that interferon-stimulated genes (ISGs) were only activated in the JCPyV-infected cells. Phosphorylated STAT1 and IRF9, which are responsible for inducing ISGs, translocated to the nucleus of JCPyV-infected cells but did not in BKPyV-infected cells. In BKPyV-infected cells, two critical suppressors of cytokine signaling, SOCS3 and SOCS1, were induced. Infection with BKPyV but not JCPyV caused reorganization of PML bodies that are associated with inactivating antiviral responses. Blockade of the interferon receptor and neutralization of soluble interferon alpha (IFN-alpha) and IFN-beta partially alleviated the block to JCPyV infection, leading to enhanced infectivity. Our results show that a type I IFN response contributes to the establishment of persistent infection by JCPyV in HRPTE cells. IMPORTANCE: The human polyomaviruses JCPyV and BKPyV both establish lifelong persistent infection in the kidneys. In immunosuppressed patients, BKPyV causes significant pathology in the kidney, but JCPyV is only rarely associated with disease in this organ. The reasons behind this striking difference in kidney pathology are unknown. In this study, we show that infection of primary human renal tubule epithelial cells with JCPyV and BKPyV results in divergent innate immune responses that control JCPyV but fail to control BKPyV. This is the first study that directly compares JCPyV and BKPyV infection in vitro in the same cell type they naturally infect, and the significant differences that have been uncovered could in part explain the distinct disease outcomes. PMID- 27381293 TI - Identification and Characterization of a Candidate Wolbachia pipientis Type IV Effector That Interacts with the Actin Cytoskeleton. AB - Many bacteria live as intracellular symbionts, causing persistent infections within insects. One extraordinarily common infection is that of Wolbachia pipientis, which infects 40% of insect species and induces reproductive effects. The bacteria are passed from generation to generation both vertically (through the oocyte) and horizontally (by environmental transmission). Maintenance of the infection within Drosophila melanogaster is sensitive to the regulation of actin, as Wolbachia inefficiently colonizes strains hemizygous for the profilin or villin genes. Therefore, we hypothesized that Wolbachia must depend on the host actin cytoskeleton. In this study, we identify and characterize a Wolbachia protein (WD0830) that is predicted to be secreted by the bacterial parasite. Expression of WD0830 in a model eukaryote (the yeast Saccharomyces cerevisiae) induces a growth defect associated with the appearance of aberrant, filamentous structures which colocalize with rhodamine-phalloidin-stained actin. Purified WD0830 bundles actin in vitro and cosediments with actin filaments, suggesting a direct interaction of the two proteins. We characterized the expression of WD0830 throughout Drosophila development and found it to be upregulated in third-instar larvae, peaking in early pupation, during the critical formation of adult tissues, including the reproductive system. In transgenic flies, heterologously expressed WD0830 localizes to the developing oocyte. Additionally, overexpression of WD0830 results in increased Wolbachia titers in whole flies, in stage 9 and 10 oocytes, and in embryos, compared to controls, suggesting that the protein may facilitate Wolbachia's replication or transmission. Therefore, this candidate secreted effector may play a role in Wolbachia's infection of and persistence within host niches. IMPORTANCE: The obligate intracellular Wolbachia pipientis is a ubiquitous alphaproteobacterial symbiont of arthropods and nematodes and is related to the rickettsial pathogens Ehrlichia spp. and Anaplasma spp. Studies of Wolbachia cell biology suggest that this bacterium relies on host actin for efficient proliferation and transmission between generations. Here, we identified and characterized a Wolbachia protein that localizes to and manipulates the eukaryotic actin cytoskeleton, is expressed by Wolbachia during host development, and alters Wolbachia titers and localization in transgenic fruit flies. We hypothesize that WD0830 may be utilized by the bacterium to facilitate replication in or invasion of different niches during host development. PMID- 27381297 TI - Light-Driven Transport of a Liquid Marble with and against Surface Flows. AB - Liquid marbles, that is, liquid drops coated by a hydrophobic powder, do not wet any solid or liquid substrate, making their transport and manipulation both highly desirable and challenging. Herein, we describe the light-driven transport of floating liquid marbles and emphasize a surprising motion behavior. Liquid marbles are deposited on a water solution containing photosensitive surfactants. Irradiation of the solution generates photoreversible Marangoni flows that transport the liquid marbles toward UV light and away from blue light when the thickness of the liquid substrate is large enough (Marangoni regime). Below a critical thickness, the liquid marbles move in the opposite direction to that of the surface flow at a speed increasing with decreasing liquid thickness (anti Marangoni). We demonstrate that the anti-Marangoni motion is driven by the free surface deformation, which propels the non-wetting marble against the surface flow. We call this behavior "slide effect". PMID- 27381296 TI - [Recurrent endocarditis due to Brevibacterium casei: case presentation and a review of the literature]. PMID- 27381298 TI - The Effects of Acute and Chronic Exercise on Skeletal Muscle Proteome. AB - Skeletal muscle plasticity and its adaptation to exercise is a topic that is widely discussed and investigated due to its primary role in the field of exercise performance and health promotion. Repetitive muscle contraction through exercise stimuli leads to improved cardiovascular output and the regulation of endothelial dysfunction and metabolic disorders such as insulin resistance and obesity. Considerable improvements in proteomic tools and data analysis have broth some new perspectives in the study of the molecular mechanisms underlying skeletal muscle adaptation in response to physical activity. In this sense, this review updates the main relevant studies concerning muscle proteome adaptation to acute and chronic exercise, from aerobic to resistance training, as well as the proteomic profile of natural inbred high running capacity animal models. Also, some promising prospects in the muscle secretome field are presented, in order to better understand the role of physical activity in the release of extracellular microvesicles and myokines activity. Thus, the present review aims to update the fast-growing exercise-proteomic scenario, leading to some new perspectives about the molecular events under skeletal muscle plasticity in response to physical activity. J. Cell. Physiol. 232: 257-269, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27381300 TI - Intersex and liver alterations induced by long-term sublethal exposure to 17alpha ethinylestradiol in adult male Cnesterodon decemmaculatus (Pisces: Poeciliidae). AB - The aim of the present study was to assess the responses of the gonopodium morphology and the gonadal and liver histology of adult male Cnesterodon decemmaculatus to sublethal long-term exposure concentrations of 17alpha ethinylestradiol (EE2). Two experiments were conducted exposing the fish to waterborne concentrations of EE2 ranging from 20 ng/L to 200 ng/L for 8 wk, 12 wk, and 16 wk. Intersex gonads were observed after 8 wk and 16 wk in fish exposed to 200 ng EE2/L and 100 ng EE2/L, respectively. Oocytes' development from testis germ cells and replacement of the efferent duct periodic acid-Schiff-positive secretion surrounding spermatozeugmata by parenchymal tissue and duct structure alterations were the major observed changes in the gonads. In contrast, no response was observed in the gonopodium morphology. Liver histology was also altered, showing increasing steatosis, single-cell necrosis to generalized necrosis, and disruption of acinar organization from 100 ng EE2/L to 200 ng EE2/L. In summary, the present results showed that although EE2 was not able to alter the morphology of a developed gonopodium, it was capable of inducing development of testicular oocytes in adult male C. decemmaculatus at environmentally relevant concentrations. Thus, externally normal but intersex C. decemmaculatus males would be expected in the wastewater-receiving streams that the species inhabits. According to the literature, the present study would be the first indicating estrogen-induced intersex in adult male poeciliid. Environ Toxicol Chem 2017;36:1738-1745. (c) 2016 SETAC. PMID- 27381299 TI - Histamine regulation of microglia: Gene-environment interaction in the regulation of central nervous system inflammation. AB - Microglia mediate neuroinflammation and regulate brain development and homeostasis. Microglial abnormalities are implicated in a range of neuropsychiatric pathology, including Tourette syndrome (TS) and autism. Histamine (HA) is both a neurotransmitter and an immune modulator. HA deficiency has been implicated as a rare cause of TS and may contribute to other neuropsychiatric conditions. In vitro studies suggest that HA can regulate microglia, but this has never been explored in vivo. We used immunohistochemistry to examine the effects of HA deficiency in histidine decarboxylase (Hdc) knockout mice and of HA receptor stimulation in wild-type animals. We find HA to regulate microglia in vivo, via the H4 receptor. Chronic HA deficiency in Hdc knockout mice reduces ramifications of microglia in the striatum and (at trend level) in the hypothalamus, but not elsewhere in the brain. Depletion of histaminergic neurons in the hypothalamus has a similar effect. Microglia expressing IGF-1 are particularly reduced, However, the microglial response to challenge with lipopolysacchariade (LPS) is potentiated in Hdc knockout mice. Genetic abnormalities in histaminergic signaling may produce a vulnerability to inflammatory challenge, setting the state for pathogenically dysregulated neuroimmune responses. PMID- 27381301 TI - Ultrafast Preparation of Monodisperse Fe3 O4 Nanoparticles by Microwave-Assisted Thermal Decomposition. AB - Thermal decomposition, as the main synthetic procedure for the synthesis of magnetic nanoparticles (NPs), is facing several problems, such as high reaction temperatures and time consumption. An improved a microwave-assisted thermal decomposition procedure has been developed by which monodisperse Fe3 O4 NPs could be rapidly produced at a low aging temperature with high yield (90.1 %). The as synthesized NPs show excellent inductive heating and MRI properties in vitro. In contrast, Fe3 O4 NPs synthesized by classical thermal decomposition were obtained in very low yield (20.3 %) with an overall poor quality. It was found for the first time that, besides precursors and solvents, magnetic NPs themselves could be heated by microwave irradiation during the synthetic process. These findings were demonstrated by a series of microwave-heating experiments, Raman spectroscopy and vector-network analysis, indicating that the initially formed magnetic Fe3 O4 particles were able to transform microwave energy into heat directly and, thus, contribute to the nanoparticle growth. PMID- 27381302 TI - [New therapies for varicose veins]. PMID- 27381303 TI - [Adult Celiac Disease]. AB - Celiac disease is an immune-mediated enteropathy in genetically predisposed individuals, triggered by gluten ingestion. Clinical manifestations include intestinal and extraintestinal symptoms. Affected individuals may also be completely asymptomatic. Nevertheless, an early diagnosis is essential in order to prevent long-term complications. Diagnostic approach involves serologic testing for tissue transglutaminase antibodies followed by duodenal biopsy in case of seropositivity. Until now, the only available treatment consists of a strict glute-free diet. Newer therapeutic strategies are currently being evaluated in clinical trials. PMID- 27381306 TI - [Medical Problems in Air Travel from a General Practitioner's Perspective]. AB - As travel by air increases, so does the number of passengers with chronic or acute medical issues. To evaluate fitness for air travel, it is necessary to consider the impact of the altered atmospheric surroundings in an airplane on the current illness to avoid a worsening of health conditions or even an emergency. As first medical contact person, the general practitioner will define supportive measures together with the patient and discuss these with the Medical Service of the airline for implementation. After a thorough evaluation, most patients will be classified fit to fly. Furthermore, a pre-travel consultation should address necessary vaccinations and information on infectious diseases. PMID- 27381305 TI - [Well-Tried and New Ones - Update Varicose Vein Treatment 2016]. AB - Venous leg symptoms are frequent, but their relevance is frequently underestimated. With the introduction of effective, minimal-invasive endovenous treatment modalities the treatment of varicose veins has recently made major advances. The basis of every treatment decision is a competent anamnesis, clinical investigation and duplex scan. Outpatient varicose vein treatment using endovenous methods has been proofed to be at least as effective as traditional varicose vein surgery but is associated with fewer adverse events. Accordingly, the endovenous methods are exspected to replace surgery as goldstandard treatment and endovenous thermal vein ablation (Laser/Radiofrequency) is accepted by the Swiss Federal Office of Public Health for general reimbursment since 1st january 2016. All currently available methods have their advantages and limitations, the individual selection based on the present symptoms, anatomic findings and patients' preferences is fundamental for an optimal treatment result and maximized patient satisfaction. PMID- 27381307 TI - [70 plus: a Challenge for the Family Doctor and the Gastroenterologist]. AB - In elderly patients, dysphagia, fecal incontinence, gastrointestinal malignant diseases and bleeding as well as ischemia of the small and large bowel are increased compared to younger patients. These diseases often significantly decrease the quality of life and survival, however, they can often be treated quite successfully if the diagnosis is made early enough. History and clinical presentation in the elderly are often unspecific, thus further investigations - especially in the emergency situation - such as laboratory examinations, abdominal ultrasound, computer tomography and endoscopy are often necessary. In elderly patients, drug therapy, endoscopic and surgical procedures must be adjusted to the biological age, the current drug therapy and the wishes of the patient and his relatives. An optimal care for elderly gastrointestinal patients is challenging for the family doctor and the gastroenterologist. PMID- 27381308 TI - [Obesity Paradox and Stroke]. AB - The obesity paradox suggests that overweight and obese patients of older age may have higher survival rates after stroke as compared to normalweight patients. However, the results need a cautious interpretation due to selection bias, treatment bias and different patients' characteristics. Moreover, randomized studies that prove a benefit of weight reduction are still lacking. As obesity is an independet risk factor for stroke, weight reduction should still be recommended in overweight patients. Randomized-controlled studies are needed to prove the effect of weight reduction on morbidity and mortality after stroke. PMID- 27381309 TI - [Cough has Many Faces]. AB - We report about a 35 year old previously apparently healthy male patient with terminal chronic renal failure due to IgA nephropathy. The initial symptoms were similar to those of a banal viral respiratory infection. Massive hypertension, orthopnea, edema and blurred vision finally led to the diagnosis of an end stage renal disease. In the renal biopsy the final stage of IgA nephropathy was detected with mostly deserted glomeruli. Hemodialysis was necessary. Among it the patient is well according to the circumstances. He is waiting for a renal transplant. PMID- 27381311 TI - [Is type 2 diabetes irreversible or can it be cured?]. PMID- 27381312 TI - Intra-articular hyaluronic injection in knee osteoarthritis only effective thanks to the placebo effect]. PMID- 27381313 TI - [CME dermatology 10: Painful inflammations in the genital area. Tinea genitalis]. PMID- 27381317 TI - A case of "atypical homicidal" cut-throat injury. AB - Cut-throats can be of homicidal, suicidal or accidental origin. In cases of death from a cut-throat, distinguishing the cause is one of the important functions in crime investigation. The features that differentiate suicidal and homicidal cut throat injuries are the presence of hesitation cuts, depth of wound, signs of struggle, edges of the wound, etc. In the case of a suicidal cut-throat, it is not uncommon to find hesitation cuts but in a homicidal cut-throat, it is uncommon. We present a case of a homicidal cut-throat injury but with hesitation cuts and tailing over the neck, unlike the classical description of homicidal cut throat injury. This resulted from a curved, sharp and moderately heavy weapon. PMID- 27381316 TI - Thoracic Aortic Graft Infections Secondary to Propionibacterium Species: Two Cases and Review of the Literature. AB - Aortic graft infections are a rare occurrence, most commonly secondary to gram positive organisms (Staphylococcus and Streptococcus species). We present 2 cases of thoracic aortic graft infections secondary to anaerobic bacteria, Propionibacterium species. The first case, a 40-year-old male, was found to have an anastomotic aneurysm at the distal anastomosis of a previous thoracoabdominal aneurysm repair. During the open repair of his anastomotic aneurysm, the original graft was not incorporated and cultures later speciated Propionibacterium acnes The second case is a 44-year-old male with a history of abdominal aortic coarctation that was repaired with a thoracic aorta to aortic bifurcation graft as a child who presented with flank pain and was found on imaging to have fluid around his bypass graft. His operating room (OR) cultures also grew out Propionibacterium species. Both patients were treated with graft excision, revascularization, and long-term antibiotics. Anaerobic bacteria are a rare cause of aortic graft infections. Upon review of the literature, these are the first 2 cases of thoracic aortic graft infections secondary to Propionibacterium species. The cultures for both patients took almost a week to speciate, highlighting the importance of following cultures long term. Anaerobic bacteria should be recognized as a cause of latent graft infections. PMID- 27381318 TI - Dual-channel microcantilever heaters for volatile organic compound detection and mixture analysis. AB - We report on novel microcantilever heater sensors with separate AlGaN/GaN heterostructure based heater and sensor channels to perform advanced volatile organic compound (VOC) detection and mixture analysis. Operating without any surface functionalization or treatment, these microcantilevers utilize the strong surface polarization of AlGaN, as well as the unique heater and sensor channel geometries, to perform selective detection of analytes based on their latent heat of evaporation and molecular dipole moment over a wide concentration range with sub-ppm detection limit. The dual-channel microcantilevers have demonstrated much superior sensing behavior compared to the single-channel ones, with the capability to not only identify individual VOCs with much higher specificity, but also uniquely detect them in a generic multi-component mixture of VOCs. In addition, utilizing two different dual channel configurations and sensing modalities, we have been able to quantitatively determine individual analyte concentration in a VOC mixture. An algorithm for complete mixture analysis, with unique identification of components and accurate determination of their concentration, has been presented based on simultaneous operation of an array of these microcantilever heaters in multiple sensing modalities. PMID- 27381319 TI - Nocardiopsissediminis sp. nov., isolated from mangrove sediment. AB - A filamentous actinomycete, designated strain 1SS5-02T, was isolated from mangrove sediment collected from Ranong province, Thailand. The strain formed aerial and substrate mycelia composed of long, branched hyphae. Aerial mycelia differentiated into non-motile, rod-shaped spores. The organism contained meso diaminopimelic acid and no diagnostic sugars in whole-cell hydrolysates. The predominant menaquinones were MK-11(H4), MK-11(H6) and MK-11(H8). Polar lipids comprised phosphatidylcholine, phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, two unidentified phospholipids and four unidentified lipids. The major fatty acids were iso-C16 : 0, C18 : 1omega9c, 10-methyl C18 : 0 and anteiso-C17 : 0. The G+C content of the genomic DNA was 73.5 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 1SS5 02T belonged to the genus Nocardiopsis. The strain showed the highest degree of 16S rRNA gene sequence similarity with 'Nocardiopsis mangrovei' HA11166 (97.9 %) and Nocardiopsis trehalosi VKM Ac-942T (97.8 %). However, strain 1SS5-02T could be distinguished from its nearest phylogenetic relatives in the genus Nocardiopsis on the basis of DNA-DNA relatedness values and the combination of phenotypic properties. On the basis of polyphasic taxonomy, strain 1SS5-02T is considered to represent a novel species of the genus Nocardiopsis, for which the name Nocardiopsis sediminis sp. nov. is proposed. The type strain is 1SS5-02T (=BCC 75410T=NBRC 110934T). PMID- 27381320 TI - Patient care will worsen, warn NHS finance chiefs. PMID- 27381321 TI - Predictors of career progression and obstacles and opportunities for non-EU hospital doctors to undertake postgraduate training in Ireland. AB - BACKGROUND: The World Health Organization's Global Code on the International Recruitment of Health Personnel urges Member States to observe fair recruitment practices and ensure equality of treatment of migrant and domestically-trained health personnel. However, international medical graduates (IMGs) have experienced difficulties in accessing postgraduate training and in progressing their careers in several destination countries. Ireland is highly dependent on IMGs, but also employs non-European Union (EU) doctors who qualified as doctors in Ireland. However, little is known regarding the career progression of these doctors. In this context, the present study assesses the determinants of career progression of non-EU doctors with particular focus on whether barriers to progression exist for those graduating outside Ireland compared to those who have graduated within. METHODS: The study utilises quantitative data from an online survey of non-EU doctors registered with the Medical Council of Ireland undertaken as part of the Doctor Migration Project (2011-2013). Non-EU doctors registered with the Medical Council of Ireland were asked to complete an online survey about their recruitment, training and career experiences in Ireland. Analysis was conducted on the responses of 231 non-EU hospital doctors whose first post in Ireland was not permanent. Career progression was analysed by means of binary logistic regression analysis. RESULTS: While some of the IMGs had succeeded in accessing specialist training, many experienced slow or stagnant career progression when compared with Irish-trained non-EU doctors. Key predictors of career progression for non-EU doctors working in Ireland showed that doctors who qualified outside of Ireland were less likely than Irish-trained non-EU doctors to experience career progression. Length of stay as a qualified doctor in Ireland was strongly associated with career progression. Those working in anaesthesia were significantly more likely to experience career progression than those in other specialities. CONCLUSIONS: The present study highlights differences in terms of achieving career progression and training for Irish trained non-EU doctors, compared to those trained elsewhere. However, the findings herein warrant further attention from a workforce planning and policy development perspective regarding Ireland's obligations under the Global Code of hiring, promoting and remunerating migrant health personnel on the basis of equality of treatment with the domestically-trained health workforce. PMID- 27381322 TI - Reduced fine-scale spatial genetic structure in grazed populations of Dianthus carthusianorum. AB - Strong spatial genetic structure in plant populations can increase homozygosity, reducing genetic diversity and adaptive potential. The strength of spatial genetic structure largely depends on rates of seed dispersal and pollen flow. Seeds without dispersal adaptations are likely to be dispersed over short distances within the vicinity of the mother plant, resulting in spatial clustering of related genotypes (fine-scale spatial genetic structure, hereafter spatial genetic structure (SGS)). However, primary seed dispersal by zoochory can promote effective dispersal, increasing the mixing of seeds and influencing SGS within plant populations. In this study, we investigated the effects of seed dispersal by rotational sheep grazing on the strength of SGS and genetic diversity using 11 nuclear microsatellites for 49 populations of the calcareous grassland forb Dianthus carthusianorum. Populations connected by rotational sheep grazing showed significantly weaker SGS and higher genetic diversity than populations in ungrazed grasslands. Independent of grazing treatment, small populations showed significantly stronger SGS and lower genetic diversity than larger populations, likely due to genetic drift. A lack of significant differences in the strength of SGS and genetic diversity between populations that were recently colonized and pre-existing populations suggested that populations colonized after the reintroduction of rotational sheep grazing were likely founded by colonists from diverse source populations. We conclude that dispersal by rotational sheep grazing has the potential to considerably reduce SGS within D. carthusianorum populations. Our study highlights the effectiveness of landscape management by rotational sheep grazing to importantly reduce genetic structure at local scales within restored plant populations. PMID- 27381324 TI - Commercial chicken breeds exhibit highly divergent patterns of linkage disequilibrium. AB - The analysis of linkage disequilibrium (LD) underpins the development of effective genotyping technologies, trait mapping and understanding of biological mechanisms such as those driving recombination and the impact of selection. We apply the Malecot-Morton model of LD to create additive LD maps that describe the high-resolution LD landscape of commercial chickens. We investigated LD in chickens (Gallus gallus) at the highest resolution to date for broiler, white egg and brown egg layer commercial lines. There is minimal concordance between breeds of fine-scale LD patterns (correlation coefficient <0.21), and even between discrete broiler lines. Regions of LD breakdown, which may align with recombination hot spots, are enriched near CpG islands and transcription start sites (P<2.2 * 10-16), consistent with recent evidence described in finches, but concordance in hot spot locations between commercial breeds is only marginally greater than random. As in other birds, functional elements in the chicken genome are associated with recombination but, unlike evidence from other bird species, the LD landscape is not stable in the populations studied. The development of optimal genotyping panels for genome-led selection programmes will depend on careful analysis of the LD structure of each line of interest. Further study is required to fully elucidate the mechanisms underlying highly divergent LD patterns found in commercial chickens. PMID- 27381323 TI - Heritable variation in maternally derived yolk androgens, thyroid hormones and immune factors. AB - Maternal reproductive investment can critically influence offspring phenotype, and thus these maternal effects are expected to be under strong natural selection. Knowledge on the extent of heritable variation in the physiological mechanisms underlying maternal effects is however limited. In birds, resource allocation to eggs is a key mechanism for mothers to affect their offspring and different components of the egg may or may not be independently adjusted. We studied the heritability of egg components and their genetic and phenotypic covariation in great tits (Parus major), using captive-bred full siblings of wild origin. Egg mass, testosterone (T) and androstenedione (A4) hormone concentrations showed moderate heritability, in agreement with earlier findings. Interestingly, yolk triiodothyronine hormone (T3), but not its precursor, thyroxine hormone (T4), concentration was heritable. An immune factor, albumen lysozyme, showed moderate heritability, but yolk immunoglobulins (IgY) did not. The genetic correlation estimates were moderate but statistically nonsignificant; a trend for a positive genetic correlation was found between A4 and egg mass, T and lysozyme and IgY and lysozyme, respectively. Interestingly, phenotypic correlations were found only between A4 and T, and T4 and T3, respectively. Given that these egg components are associated with fitness-related traits in the offspring (and mother), and that we show that some components are heritable, it opens the possibility that natural selection may shape the rate and direction of phenotypic change via egg composition. PMID- 27381325 TI - Complementary sex determination, inbreeding depression and inbreeding avoidance in a gregarious sawfly. AB - Although most Hymenoptera reproduce via arrhenotokous haplodiploidy, the underlying genetic mechanisms vary. Of these, the most widespread mechanism appears to be single-locus complementary sex determination (sl-CSD), in which individuals that are diploid and heterozygous at a sex-determining locus are female, and individuals that are homozygous or hemizygous are male. Because inbreeding increases the probability of producing diploid males, which are often sterile or inviable, sl-CSD can generate substantial inbreeding depression. To counteract this, Hymenoptera with traits that promote inbreeding, such as gregariousness, may evolve one or more of the following: inbreeding avoidance, functional diploid males or alternative sex determination mechanisms. Here, we investigate sex determination, inbreeding depression and inbreeding avoidance in Neodiprion lecontei, a gregarious, pine-feeding sawfly in the family Diprionidae. First, via inbreeding experiments and flow cytometry, we demonstrate that this species has CSD. By modeling expected sex ratios under different conditions, we also show that our data are consistent with sl-CSD. Second, via tracking survival in inbred and outbred families, we demonstrate that inbred families have reduced larval survival and that this mortality is partly attributable to the death of diploid males. Third, using a no-choice mating assay, we demonstrate that females are less willing to mate with siblings than nonsiblings. Together, these results suggest that inbreeding depression stemming from CSD has shaped mating behavior in N. lecontei. These results also set the stage for future comparative work that will investigate the interplay between sex determination, ecology and behavior in additional diprionid species that vary in larval gregariousness. PMID- 27381326 TI - Mid to distal third tibial shaft fractures caused by gunshots: Characterization and incidence of distal intra-articular extension. AB - INTRODUCTION: Spiral tibial shaft fractures are known to have a high rate of distal intra-articular extension; however, the risk of joint involvement caused by gunshots has not been thoroughly evaluated. The purpose of this study was to determine the incidence of intra- articular involvement in tibial shaft fractures caused by gunshots. The secondary purpose of this study was to assess the usefulness of ankle radiographs versus computed tomography (CT) scans in identifying these fractures. MATERIALS AND METHODS: Ninety consecutive patients were identified as having a tibia fracture caused by gunshot at a Level-1 trauma center. Forty-four of these patients were fractures of the mid to distal third shaft. Twenty-eight patients had ankle CT scans available for review, and 24 patients had dedicated ankle films. Three orthopaedic surgeons and a radiologist read the radiographs and CT scans. Sensitivity and specificity analysis was performed for the ankle radiographs using ankle CT scans as the gold standard. RESULTS: Seven of the twenty-eight fractures evaluated with a CT scan proved to have intra-articular involvement (Prevalence: 25%, 95% CI: 11.4%-45.2%). One of the seven intra-articular fractures was not seen on dedicated ankle radiographs (14.3%). The sensitivity of diagnosing an intra-articular extension on ankle radiographs was 0.85, 95%CI: 0.42-0.99. The specificity of diagnosing an intra articular extension on ankle radiographs was 1.00, 95%CI: 0.81-1.00. Of the seven intra-articular fractures, three required additional treatment to address the intra-articular extension. CONCLUSION: The incidence of intra-articular involvement for tibial shaft fractures secondary to gunshot is less than that reported for spiral type fractures (11-45% vs. 25-58%). Although radiographs have a high specificity, the sensitivity is lower than expected, with worse outcomes if a fracture is missed. We recommend that a CT scan should be utilized to determine intra-articular extension in the setting of tibial shaft fractures caused by gunshots. PMID- 27381327 TI - Holistic ultrasound in trauma: An update. AB - Holistic ultrasound is a total body examination using an ultrasound device aiming to achieve immediate patient care and decision making. In the setting of trauma, it is one of the most fundamental components of care of the injured patients. Ground-breaking imaging software allows physicians to examine various organs thoroughly, recognize imaging signs early, and potentially foresee the onset or the possible outcome of certain types of injuries. Holistic ultrasound can be performed on a routine basis at the bedside of the patients, at admission and during the perioperative period. Trauma care physicians should be aware of the diagnostic and guidance benefits of ultrasound and should receive appropriate training for the optimal management of their patients. In this paper, the findings of holistic ultrasound in trauma patients are presented, with emphasis on the lungs, heart, cerebral circulation, abdomen, and airway. Additionally, the benefits of ultrasound imaging in interventional anaesthesia techniques such as ultrasound-guided peripheral nerve blocks and central vein catheterization are described. PMID- 27381328 TI - Clinical implications of impingement of the anterior femoral cortex after cephalomedullary nailing. AB - BACKGROUND: Cortical impingement is a common complication after cephalomedullary nailing, but the evidence about its consequences is very limited. The aim of this study was to assess the clinical implications of cortical impingement on patients treated with cephalomedullary nails. METHODS: A cohort study was carried out at a Level I academic Institution with consecutive patients treated with cephalomedullary nails during 2010 and 2013. Demographic and nail variables were recorded as well as cortical impingement was determined on the radiographs. Clinical outcomes such as pain, femoral fractures, and delayed or nonunion of the fracture were detected during the follow-up. The follow-up was divided into short (6-12 months), medium- (12.1-36 months), and long-term follow-up (>=36.1months). Descriptive statistics were used, and Chi-square or Fisher's exact tests measured the association between categorical variables. The Mann-Whitney U test was performed to evaluate differences between cortical impingement in terms of pain, and pain and the follow-up categories. RESULTS: A total of 119 patients were analyzed with a mean age of 74.8 years+/-17.1, and a mean follow-up of 23.5 months+/-12.1. Overall the pain was present in 61 (51.2%) cases, and it was observed in 28/59 (47.4%) and 33/60 (55%) of the patients with presence or absence of cortical impingement respectively. There was not a statistically significant association between cortical impingement and pain (p=0.20), neither differences were detected between pain and the follow-up groups (p=0.48). Out of 59 cases with cortical impingement, femoral fractures were observed in two patients (3.3%), and delayed union of the fractures was seen in two patients who did not present impingement. Since patients with delayed union received treatment as soon as it was diagnosed, no cases of nonunion of fractures were identified. CONCLUSIONS: Cortical impingement of the anterior cortex of the femur was not associated with the presence of pain, so that other causes should be assessed to explain the pain after 6 months of being treated with a cephalomedullary nail. Femoral fractures, and delayed union or nonunion of the fracture may occur theoretically in patients with cortical impingement. PMID- 27381329 TI - Anti-inflammatory effect of conditioned medium from human uterine cervical stem cells in uveitis. AB - The aim of the present study was to evaluate the effect of conditioned medium from human uterine cervical stem cells (CM-hUCESCs) in uveitis. To do that, uveitis was induced in rats after footpad injection of Escherichia coli lipopolysaccaride (LPS). Human retinal pigment epithelial (ARPE-19) cells after LPS challenge were used to test anti-inflammatory effect of CM-hUCESCs 'in vitro'. Real-time PCR was used to evaluate mRNA expression levels of the pro inflammatory cytokines interkeukin-6, interkeukin-8, macrophage inflammatory protein-1 alpha, tumor necrosis factor alpha, and the anti-inflammatory interkeukin-10. Leucocytes from aqueous humor (AqH) were quantified in a Neubauer chamber, and eye histopathological analysis was done with hematoxylin-eosin staining. Additionally, using a human cytokine antibody array we evaluated CM hUCESCs to determine mediating proteins. Results showed that administration of CM hUCESCs significantly reduced LPS-induced pro-inflammatory cytokines both 'in vitro' and 'in vivo', and decreased leucocytes in AqH and ocular tissues. High levels of cytokines with anti-inflammatory effects were found in CM-hUCESCs, suggesting a possible role of these factors in reducing intraocular inflammation. In summary, treatment with CM-hUCESCs significantly reduces inflammation in uveitis. Our data indicate that CM-hUCESCs could be regarded as a potential therapeutic agent for patients suffering from ocular inflammation. PMID- 27381331 TI - [Proposals for the study of the second victim phenomenon in Spanish Primary Care Centres and Hospitals]. AB - OBJECTIVE: To identify the Spanish studies conducted since 2014 on second victims. Its main objective was to identify a global response to the second victim problem, assessing the impact of adverse events (AE) on caregivers and developing of a set of tools to reduce their impact. METHOD: Descriptive studies in which a sample of managers and safety coordinators from Hospitals and Primary Care were surveyed to determine the activities being carried out as regards second victims, as well as a sample of health professionals to describe their experience as a second victims. Qualitative studies are included to design a guide of recommended actions following an AE, an online awareness program on this phenomenon, an application (app) with activities on safety that are the responsibility of the managers, and a web tool for the analysis of AEs. RESULTS: A total of 1,493 professionals (managers, safety coordinators and caregivers) from eight Spanish regions participated. The guide of recommendations, the online program, and the developed applications are accessible on the website: www.segundasvictimas.es, which has received more than 2,500 visits in one year. DISCUSSION: Study results represent a starting point in the study of the second victim phenomenon in Spain. The tools developed raise the awareness of the medical healthcare community about this problem, and provide professionals with basic skills to manage the impact of AEs. PMID- 27381330 TI - Vermamoeba vermiformis-Aspergillus fumigatus relationships and comparison with other phagocytic cells. AB - Free living amoebae (FLA) are protists ubiquitously present in the environment. Aspergillus fumigatus is a mould responsible for severe deep-seated infections, and that can be recovered in the same habitats as the FLA. By conducting coculture experiments and fungal incubation with amoebal supernatants, we report herein that Vermamoeba vermiformis, a FLA present in hospital water systems, promotes filamentation and growth of A. fumigatus. This finding is of particular importance to institutions whose water systems might harbor FLA and could potentially be used by immunocompromised patients. Also, the relationships between V. vermiformis and A. fumigatus were compared to those between this fungus and two other phagocytic cells: Acanthamoeba castellanii, another FLA, and macrophage-like THP-1 cells. After 4 h of coincubation, the percentages of the three phagocytic cell types with adhered conidia were similar, even though the types of receptors between FLA and macrophagic cell seemed different. However, the percentage of THP-1 with internalized conidia was considerably lower (40 %) in comparison with the two other cell types (100 %). Thus, this study revealed that interactions between A. fumigatus and these three phagocytic cell types show similarities, even though it is premature to extrapolate these results to interpret relationships between A. fumigatus and macrophages. PMID- 27381333 TI - Catalase in Leishmaniinae: With me or against me? AB - The catalase gene is a virtually ubiquitous component of the eukaryotic genomes. It is also present in the monoxenous (i.e. parasitizing solely insects) trypanosomatids of the subfamily Leishmaniinae, which have acquired the enzyme by horizontal gene transfer from a bacterium. However, as shown here, the catalase gene was secondarily lost from the genomes of all Leishmania sequenced so far. Due to the potentially key regulatory role of hydrogen peroxide in the inter stagial transformation of Leishmania spp., this loss seems to be a necessary prerequisite for the emergence of a complex life cycle of these important human pathogens. Hence, in this group of protists, the advantages of keeping catalase were uniquely outweighed by its disadvantages. PMID- 27381334 TI - Kraft Lignin Biodegradation by Dysgonomonas sp. WJDL-Y1, a New Anaerobic Bacterial Strain Isolated from Sludge of a Pulp and Paper Mill. AB - Wastewater containing kraft lignin (KL) discharged from pulp and paper industries could cause serious environmental contamination. Appropriate effluent treatment is required to reduce the pollution. Investigations on anaerobic bacteria capable of degrading KL are beneficial to both lignin removal and biofuel regeneration from the effluent. In this paper, an anaerobic strain capable of degrading KL was isolated from the sludge of a pulp and paper mill and identified as Dysgonomonas sp. WJDL-Y1 by 16S rRNA analysis. Optimum conditions for KL degradation by strain WJDL-Y1 were obtained at initial pH of 6.8, C:N ratio of 6 and temperature of 33 degrees C, based on statistical analyses by response surface methodology. For a 1.2 g/l KL solution, a COD removal rate of 20.7% concomitant with biomass increase of 17.6% was achieved after 4 days of incubation under the optimum conditions. After the treatment by strain WJDL-Y1, KL was modified and degraded. PMID- 27381335 TI - Biological Potential of Bioorganic Fertilizer Fortified with Bacterial Antagonist for the Control of Tomato Bacterial Wilt and the Promotion of Crop Yields. AB - The application of Bacillus sp. in the biological control of plant soilborne diseases has been shown to be an environmentally friendly alternative to the use of chemical fungicides. In this study, the effects of bioorganic fertilizer (BOF) fortified with Bacillus amyloliquefaciens SQY 162 on the suppression of tomato bacterial wilt were investigated in pot experiments. The disease incidence of tomato wilt after the application of BOF was 65.18% and 41.62% lower at 10 and 20 days after transplantation, respectively, than in the control condition. BOF also promoted the plant growth. The SQY 162 populations efficiently colonized the tomato rhizosphere, which directly suppressed the number of Ralstonia solanacearum in the tomato rhizosphere soil. In the presence of BOF, the activities of defense-related enzymes in tomato were lower than in the presence of the control treatment, but the expression levels of the defense-related genes of the plants in the salicylic acid and jasmonic acid pathways were enhanced. It was also found that strain SQY 162 could secrete antibiotic surfactin, but not volatile organic compounds, to suppress Ralstonia. The strain could also produce plant growth promotion compounds such as siderophores and indole-3-acetic acid. Thus, owing to its innate multiple-functional traits and its broad biocontrol activities, we found that this antagonistic strain isolated from the tobacco rhizosphere could establish itself successfully in the tomato rhizosphere to control soilborne diseases. PMID- 27381332 TI - Study protocol for a systematic review of evidence for lifestyle interventions targeting smoking, sleep, alcohol/other drug use, physical activity, and healthy diet in people with bipolar disorder. AB - BACKGROUND: People with bipolar disorder (BD) have a mortality gap of up to 20 years compared to the general population. Physical conditions, such as cardiovascular disease (CVD) and cancer, cause the majority of excess deaths in psychiatric populations and are the leading causes of mortality in people with BD. However, comparatively little attention has been paid to reducing the risk of physical conditions in psychiatric populations. Unhealthy lifestyle behaviors are among the potentially modifiable risk factors for a range of commonly comorbid chronic medical conditions, including CVD, diabetes, and obesity. This systematic review will identify and evaluate the available evidence for effective interventions to reduce risk and promote healthy lifestyle behaviors in BD. METHODS/DESIGN: We will search MEDLINE, Embase, PsychINFO, Cochrane Database of Systematic Reviews, and CINAHL for published research studies (with at least an abstract published in English) that evaluate behavioral or psychosocial interventions to address the following lifestyle factors in people with BD: tobacco use, physical inactivity, unhealthy diet, overweight or obesity, sleep wake disturbance, and alcohol/other drug use. Primary outcomes for the review will be changes in tobacco use, level of physical activity, diet quality, sleep quality, alcohol use, and illicit drug use. Data on each primary outcome will be synthesized across available studies in that lifestyle area (e.g., tobacco abstinence, cigarettes smoked per day), and panel of research and clinical experts in each of the target lifestyle behaviors and those experienced with clinical and research with individuals with BD will determine how best to represent data related to that primary outcome. Seven members of the systematic review team will extract data, synthesize the evidence, and rate it for quality. Evidence will be synthesized via a narrative description of the behavioral interventions and their effectiveness in improving the healthy lifestyle behaviors in people with BD. DISCUSSION: The planned review will synthesize and evaluate the available evidence regarding the behavioral or psychosocial treatment of lifestyle-related behaviors in people with BD. From this review, we will identify gaps in our existing knowledge and research evidence about the management of unhealthy lifestyle behaviors in people with BD. We will also identify potential opportunities to address lifestyle behaviors in BD, with a view to reducing the burden of physical ill-health in this population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015019993. PMID- 27381336 TI - Effect of the Shape and Size of Quorum-Quenching Media on Biofouling Control in Membrane Bioreactors for Wastewater Treatment. AB - Recently, spherical beads entrapping quorum quenching (QQ) bacteria have been reported as effective moving QQ-media for biofouling control in MBRs for wastewater treatment owing to their combined effects of biological (i.e., quorum quenching) and physical washing. Taking into account both the mass transfer of signal molecules through the QQ-medium and collision efficiencies of the QQ medium against the filtration membranes in a bioreactor, a cylindrical medium (QQ cylinder) was developed as a new shape of moving QQ-medium. The QQ-cylinders were compared with previous QQ-beads in terms of the QQ activity and the physical washing effect under identical loading volumes of each medium in batch tests. It was found that the QQ activity of a QQ-medium was highly dependent on its specific surface area, regardless of the shape of the medium. In contrast, the physical washing effect of a QQ-medium was greatly affected by its geometric structure. The enhanced anti-biofouling property of the QQ-cylinders relative to QQ-beads was confirmed in a continuous laboratory-scale MBR with a flat-sheet membrane module. PMID- 27381337 TI - Effects of Quorum Quenching on the Microbial Community of Biofilm in an Anoxic/Oxic MBR for Wastewater Treatment. AB - Recently, bacterial quorum quenching (QQ) has been proven to have potential as an innovative approach for biofouling control in membrane bioreactors (MBRs) for advanced wastewater treatment. Although information regarding the microbial community is crucial for the development of QQ strategies, little information exists on the microbial ecology in QQ-MBRs. In this study, the microbial communities of biofilm were investigated in relation to the effect of QQ on anoxic/oxic MBRs. Two laboratory-scale MBRs were operated with and without QQ beads (QQ-bacteria entrapped in beads). The transmembrane pressure increase in the QQ-MBRs was delayed by approximately 100-110% compared with conventional- and vacant-MBRs (beads without QQ-bacteria) at 45 kPa. In terms of the microbial community, QQ gradually favored the development of a diverse and even community. QQ had an effect on both the bacterial composition and change rate of the bacterial composition. Proteobacteria and Bacteroidetes were the most dominant phyla in the biofilm, and the average relative composition of Proteobacteria was low in the QQ-MBR. Thiothrix sp. was the dominant bacterium in the biofilm. The relative composition of Thiothrix sp. was low in the QQ-MBR. These findings provide useful information that can inform the development of a new QQ strategy. PMID- 27381338 TI - Bacterial Population in Intestines of Litopenaeus vannamei Fed Different Probiotics or Probiotic Supernatant. AB - The interactions of microbiota in the gut play an important role in promoting or maintaining the health of hosts. In this study, in order to investigate and compare the effects of dietary supplementation with Lactobacillus pentosus HC-2 (HC-2), Enterococcus faecium NRW-2, or the bacteria-free supernatant of a HC-2 culture on the bacterial composition of Litopenaeus vannamei, Illumina sequencing of the V1-V2 region of the 16S rRNA gene was used. The results showed that unique species exclusively existed in specific dietary groups, and the abundance of Actinobacteria was significantly increased in the intestinal bacterial community of shrimp fed with the bacteria-free supernatant of an HC-2 culture compared with the control. In addition, the histology of intestines of the shrimp from the four dietary groups was also described, but no obvious improvements in the intestinal histology were observed. The findings in this work will help to promote the understanding of the roles of intestinal bacteria in shrimps when fed with probiotics or probiotic supernatant. PMID- 27381339 TI - Microbial Community of Healthy Thai Vegetarians and Non-Vegetarians, Their Core Gut Microbiota, and Pathogen Risk. AB - Pyrosequencing analysis of intestinal microflora from healthy Thai vegetarians and non-vegetarians exhibited 893 OTUs covering 189 species. The strong species indicators of vegetarians and non-vegetarians were Prevotella copri and Bacteroides vulgatus as well as bacteria close to Escherichia hermanii with % relative abundance of 16.9 and 4.5-4.7, respectively. Core gut microbiota of the vegetarian and non-vegetarian groups consisted of 11 and 20 different bacterial species, respectively, belonging to Actinobacteria, Firmicutes, and Proteobacteria commonly found in both groups. Two species, Faecalibacterium prausnitzii and Gemmiger formicilis, had a prevalence of 100% in both groups. Three species, Clostridium nexile, Eubacterium eligens, and P. copri, showed up in most vegetarians, whereas more diversity of Collinsella aerofaciens, Ruminococcus torques, various species of Bacteroides, Parabacteroides, Escherichia, and different species of Clostridium and Eubacterium were found in most non-vegetarians. Considering the correlation of personal characters, consumption behavior, and microbial groups, the age of non-vegetarians showed a strong positive correlation coefficient of 0.54 (p = 0.001) to Bacteroides uniformis but exhibited a moderate one to Alistipes finegoldii and B. vulgatus. Only a positive moderate correlation of body mass index and Parabacteroides distasonis appeared. Based on the significant abundance of potential pathogens, the microbiota of the non-vegetarian group showed an abundance of potential pathogen varieties of Bilophila wadsworthia, Escherichia coli, and E. hermannii, whereas that of the vegetarian group served for only Klebsiella pneumoniae. These results implied that the microbiota of vegetarians with high abundance of P. copri and low potential pathogen variety would be a way to maintain good health in Thais. PMID- 27381340 TI - The severity of ventricular arrhythmia correlates with the extent of myocardial sympathetic denervation, but not with myocardial fibrosis extent in chronic Chagas cardiomyopathy : Chagas disease, denervation and arrhythmia. AB - BACKGROUND: To investigate the correlation between the extent of myocardial sympathetic denervation and fibrosis and the presence of degrees of severity of ventricular arrhythmias in chronic Chagas cardiomyopathy (CCC). METHODS: Forty three CCC patients with left ventricular ejection fraction (LVEF) >= 35% were divided into three groups: SVT group-presenting Sustained Ventricular Tachycardia (SVT) (n = 15), NSVT group-exhibiting episodes of non-SVT (NSVT) on 24-h Holter monitoring (n = 11), and Control group-exhibiting neither SVT nor episodes of NSVT (n = 17). The patients underwent SPECT imaging for myocardial sympathetic innervation with 123Iodine-MIBG (MIBG) and myocardial perfusion with 99mTc Sestamibi (MIBI) for the evaluation of regional myocardial fibrosis. RESULTS: The summed rest perfusion scores were similar in the three groups. The summed difference score between MIBG and MPI images, which evaluated the extent of denervated but viable myocardium, was significantly higher in SVT group (20.0 +/- 8.0) as compared with the control group (2.0 +/- 5.0, P < .0001) and with the NSVT group (11.0 +/- 8.0, P < .05). CONCLUSIONS: The occurrence of ventricular arrhythmias of different degrees of severity correlates quantitatively with the extent of cardiac sympathetic denervation, but not with the extent of fibrosis, suggesting that myocardial sympathetic denervation plays a major role in triggering ventricular arrhythmia in CCC. PMID- 27381341 TI - Prediction of 14-year cardiovascular outcomes by dobutamine stress 99mTc tetrofosmin myocardial perfusion SPECT in elderly patients unable to perform exercise testing. AB - BACKGROUND: Dobutamine stress myocardial perfusion imaging (MPI) is a useful alternative for the evaluation of coronary artery disease (CAD) in elderly patients who are unable to perform an exercise stress test. However, data on the long-term prognostic value of stress MPI in elderly patients are lacking. Therefore, this study evaluated the long-term prognostic value of dobutamine stress MPI in elderly patients unable to perform an exercise test. METHODS: The study population consisted of 247 elderly patients (mean age 71 +/- 5 years) who underwent dobutamine stress single-photon emission computed tomography (SPECT) MPI. An abnormal SPECT study was defined as the presence of fixed and/or reversible perfusion defects. A summed stress score (SSS) was obtained to estimate the extent and severity of perfusion defects. End points during follow up were all-cause mortality, cardiac mortality, and nonfatal myocardial infarction (MI). RESULTS: During a median follow-up of 14 years (range 12-16), 168 (68%) patients died (all-cause mortality), of which 56 (23%) were due to cardiac causes. Nonfatal MI occurred in 19 (8%) patients. Kaplan-Meier survival curves showed that MPI provided optimal risk stratification in patients with normal and abnormal MPI. Multivariable analysis identified an abnormal MPI as a strong significant predictor of all-cause mortality and cardiac events. A multivariable analysis also revealed that a reversible defect and SSS were strong long-term predictors of cardiac mortality and hard cardiac events. CONCLUSION: Dobutamine stress 99mTc-tetrofosmin SPECT provides incremental prognostic information for the prediction of long-term cardiovascular outcomes in elderly patients, unable to perform exercise testing. Dobutamine stress MPI is useful in risk classifying elderly patients. PMID- 27381342 TI - SIFORM: shared informative factor models for integration of multi-platform bioinformatic data. AB - MOTIVATION: High-dimensional omic data derived from different technological platforms have been extensively used to facilitate comprehensive understanding of disease mechanisms and to determine personalized health treatments. Numerous studies have integrated multi-platform omic data; however, few have efficiently and simultaneously addressed the problems that arise from high dimensionality and complex correlations. RESULTS: We propose a statistical framework of shared informative factor models that can jointly analyze multi-platform omic data and explore their associations with a disease phenotype. The common disease associated sample characteristics across different data types can be captured through the shared structure space, while the corresponding weights of genetic variables directly index the strengths of their association with the phenotype. Extensive simulation studies demonstrate the performance of the proposed method in terms of biomarker detection accuracy via comparisons with three popular regularized regression methods. We also apply the proposed method to The Cancer Genome Atlas lung adenocarcinoma dataset to jointly explore associations of mRNA expression and protein expression with smoking status. Many of the identified biomarkers belong to key pathways for lung tumorigenesis, some of which are known to show differential expression across smoking levels. We discover potential biomarkers that reveal different mechanisms of lung tumorigenesis between light smokers and heavy smokers. AVAILABILITY AND IMPLEMENTATION: R code to implement the new method can be downloaded from http://odin.mdacc.tmc.edu/jhhu/ CONTACT: jhu@mdanderson.org. PMID- 27381343 TI - Peromyscus as a model system for understanding the regulation of maternal behavior. AB - The genus Peromyscus has been used as a model system for understanding maternal behavior because of the diversity of reproductive strategies within this genus. This review will describe the ecological factors that determine litter size and litter quality in polygynous species such as Peromyscus leucopus and Peromyscus maniculatus. We will also outline the physiological and social factors regulating maternal care in Peromyscus californicus, a monogamous and biparental species. Because biparental care is relatively rare in mammals, most research in P. californicus has focused on understanding the biology of paternal care while less research has focused on understanding maternal care. As a result, the social, sensory, and hormonal cues used to coordinate parental care between male and female P. californicus have been relatively well-studied. However, less is known about the physiology of maternal care in P. californicus and in other Peromyscus species. The diversity of the genus Peromyscus provides the potential for future research to continue to examine how variation in social systems has shaped the mechanisms that underlie maternal care. PMID- 27381344 TI - Mammalian microRNAs and long noncoding RNAs in the host-bacterial pathogen crosstalk. AB - Gene expression regulation is a critical question in host-pathogen interactions, and RNAs act as key players in this process. In this review, we focus on the mammalian RNA response to bacterial infection, with a special interest on microRNAs and long non-coding RNAs. We discuss the role of cellular miRNAs in immunity, the implication of circulating miRNAs as well as the influence of the microbiome on the miRNA response. We also review how pathogens counteract the host miRNA expression. Interestingly, bacterial non-coding RNAs regulate host gene expression and conversely eukaryotic miRNAs may regulate bacterial gene expression. Overall, the characterization of RNA regulatory networks represents an emerging theme in the field of host pathogen interactions. PMID- 27381346 TI - Brain tumour presenting with burns: Case report and discussion. AB - Descriptions of burns as the presenting features of underlying neurological pathology are very rare, with only two previously published case reports available. Both of these reports featured meningioma as the pre-existing pathology and both described burn excision and wound healing, prior to surgical tumour ablation. The authors describe the case of a 35-year-old female, who presented with 25% total body surface area burns and recent global neurological deterioration. MRI imaging revealed a large intracranial tumour. Multidisciplinary management included rigorous non-surgical burn wound care and early craniotomy and tumour excision. This proceeded without complication. Burn excision and skin grafting was carried out successfully, two weeks later. This case differs from the previous two reported cases, which both described burn excision, as a pre-requisite to neurosurgery. This case establishes that the presence of a burn wound is not a total contra-indication to intracranial surgery. PMID- 27381345 TI - Infection resistance and tolerance in Peromyscus spp., natural reservoirs of microbes that are virulent for humans. AB - The widely-distributed North American species Peromyscus leucopus and P. maniculatus of cricetine rodents are, between them, important natural reservoirs for several zoonotic diseases of humans: Lyme disease, human granulocytic anaplasmosis, babesiosis, erhlichiosis, hard tickborne relapsing fever, Powassan virus encephalitis, hantavirus pulmonary syndrome, and plague. While these infections are frequently disabling and sometimes fatal for humans, the peromyscines display little pathology and apparently suffer few consequences, even when prevalence of persistent infection in a population is high. While these Peromyscus spp. are unable to clear some of the infections, they appear to have partial resistance, which limits the burden of the pathogen. In addition, they display traits of infection tolerance, which reduces the damage of the infection. Research on these complementary resistance and tolerance phenomena in Peromyscus has relevance both for disease control measures targeting natural reservoirs and for understanding the mechanisms of the comparatively greater sickness of many humans with these and other infections. PMID- 27381347 TI - Methotrexate induced pneumatosis intestinalis under hemodialysis patient. AB - Pneumatosis intestinalis (PI) is a rare disorder characterized by the gas within the intestinal mucosa. This is the first report methotrexate (MTX) induced PI under hemodialysis (HD) patient. A 46-year-old man suffered rheumatoid arthritis and underwent HD at local HD center. After the initial induction of MTX, the patient showed epigastralgia and diarrhea. He was referred to our hospital and abdominal computed tomography showed significant large intestinal edema and free intraperitoneal air consistent with PI. Physicians should aware that MTX is contraindication drug for chronic kidney disease and high-flux HD may decrease MTX toxicity and oxidative stress, improving PI. PMID- 27381350 TI - Interaction of TGA@CdTe Quantum Dots with an Extracellular Matrix of Haematococcus pluvialis Microalgae Detected Using Surface-Enhanced Raman Spectroscopy (SERS). AB - The present study reports the localization and interaction of thioglycolic acid (TGA) capped CdTe quantum dots (TGA@CdTe QDs) within the extracellular matrix (ECM) of Haematococcus pluvialis (Chlorophyceae) microalgae (HPM) after an incubation period of 5 min. Changes in the Raman spectrum of HPM induced by the adsorption of the TGA@CdTe QDs are successfully found by using naked gold anisotropic structures as nano-sensors for surface-enhanced Raman scattering (SERS effect). Raman spectroscopy results show that TGA@CdTe QDs interact with the biomolecules present in the ECM. Sample preparation and characterization by complementary techniques such as confocal and electron microscopy are also used to confirm the presence and localization of the nanoparticles in the algae. This research shows new evidence on early accumulation of QDs in plant cells and would further improve our understanding about their environmental impact. PMID- 27381349 TI - Diabetes related knowledge, self-care behaviours and adherence to medications among diabetic patients in Southwest Ethiopia: a cross-sectional survey. AB - BACKGROUND: The provision of health education involving self-care and good adherence to medications has been acknowledged to be a cost effective strategy for improving quality of life of diabetes patients. We assessed levels of knowledge about type 2 diabetes mellitus (T2DM), self-care behaviours and adherence to medication among DM patients. METHODS: A facility based cross sectional survey of 325 adults with T2DM patients attending Jimma University Teaching Hospital, Southwest Ethiopia was conducted. We used diabetes Knowledge Test, Expanded Version of the Summary of Diabetes Self-Care Activities and Morisky 8-Item medication adherence as tools to measure diabetic knowledge, self care behaviours and adherence to medications respectively. Multinomial logistic regression analyses were used to assess the independent predictors of diabetes knowledge and adherence to medications. The binary logistic regression was applied for self-care behaviours. RESULTS: 309 respondents were included in the survey. Of all the respondents, 44.9 %, 20.1 % and 34.9 % had low, medium and high level diabetic knowledge respectively. High level of diabetic knowledge was the reference group. Being illiterate (AOR = 3.1, 95%CI: 1.03-9.3), having BMI <18 kg/m(2) (AOR = 6.4, 95%CI: 1.2-34.9) and duration of DM < 5 years (AOR = 4.2, 95%CI: 1.9-9.5) were significantly associated with low level of diabetic knowledge. T2DM patients who practiced good self-care (AOR = 0.5, 95%CI: 0.3-0.9) were less likely to have low knowledge. Duration of DM < 5 years (AOR = 9.8, 95%CI: 3.2-30.2) was significantly associated with medium level of diabetic knowledge. 157(50.8 %) patients had poor self-care behaviour and this was associated with level of education and adherence to medication. The proportions of patients with low, medium and high adherence to medication were 24.9 %, 37.9 % and 37.2 % respectively. Being a merchant, having medium level of diabetic knowledge and having good glycemic control level were associated with low adherence to medications. CONCLUSIONS: Significant number of DM patients had low level of knowledge, poor self-care behaviours and low level of adherence to medications. These findings call for the need of integrated interventional management on diabetic knowledge, self-care behaviours and adherence to medications. To ensure effective T2DM management, a strategic approach that improves health literacy could be a cross cutting intervention. PMID- 27381348 TI - An emerging zoonotic clone in the Netherlands provides clues to virulence and zoonotic potential of Streptococcus suis. AB - Streptococcus suis is a zoonotic swine pathogen and a major public health concern in Asia, where it emerged as an important cause of bacterial meningitis in adults. While associated with food-borne transmission in Asia, zoonotic S. suis infections are mainly occupational hazards elsewhere. To identify genomic differences that can explain zoonotic potential, we compared whole genomes of 98 S. suis isolates from human patients and pigs with invasive disease in the Netherlands, and validated our observations with 18 complete and publicly available sequences. Zoonotic isolates have smaller genomes than non-zoonotic isolates, but contain more virulence factors. We identified a zoonotic S. suis clone that diverged from a non-zoonotic clone by means of gene loss, a capsule switch, and acquisition of a two-component signalling system in the late 19th century, when foreign pig breeds were introduced. Our results indicate that zoonotic potential of S. suis results from gene loss, recombination and horizontal gene transfer events. PMID- 27381351 TI - Optical Characterization of Parathyroid Tissues. AB - The parathyroid glands are small and often similar to lymph nodes, fat, and thyroid tissue. These glands are difficult to identify during surgery and a biopsy of the parathyroid for identification can lead to damage of the gland. The use of static and time-resolved fluorescence techniques to detect biochemical composition and tissue structure alterations could help to develop a portable, minimally invasive, and nondestructive method to assist medical evaluation of parathyroid tissues. In this study, we investigated 10 human parathyroid samples by absorbance, fluorescence, excitation, and time-resolved fluorescence measurements. Moreover, we compared the results of time-resolved fluorescence measurements with 59 samples of thyroid tissues. The fluorescence lifetimes with emission at 340 nm were 1.09 +/- 0.10 and 4.46 +/- 0.06 ns for healthy tissue, 1.01 +/- 0.25 and 4.39 +/- 0.36 ns for benign lesions, and 0.67 +/- 0.36 and 3.92 +/- 0.72 ns for malignant lesions. The lifetimes for benign and malignant lesions were significantly different, as attested by the analysis of variance with confidence levels higher than 87%. For each class of samples (healthy, benign, and malignant) we perceived statistical differences between the thyroid and parathyroid tissue, independently. After further investigations, fluorescence methods could become a tool to identify normal and pathological parathyroid tissues and distinguish thyroid from parathyroid tissues. PMID- 27381352 TI - Influence of Sampling Component on Determination of Soluble Solids Content of Fuji Apple Using Near-Infrared Spectroscopy. AB - Fuji apples from two production areas were separated into six batches by different experimenters. After applying light (500-1010 nm) on the surface of intact ones for their visible and near-infrared (NIR) spectra, destructive samples of three apple components were taken to determine the soluble solids content (SSC). Correlation and regression coefficients between the second Savitzky-Golay derivative of the spectra and SSC were analyzed to reveal that SSC values derived from the different apple components showed significantly different responses in the visible region. However, similar responses, particularly in the NIR section (730-932 nm), remained, including two sugar bands at 890 and 906 nm. On the basis of applying above characteristic bands to remove the interference signals, partial least square (PLS) and multiple linear regression (MLR) showed similar effective performances. According to the analysis of variance (ANOVA) method, sampling methods had significant effect on quantitative accuracy, and the model, using SSC values detected from the outer flesh cuboid (2.5 * 2.5 * 1.5 cm3), provided the best performance with lower root mean square error of prediction and higher correlation coefficient. PMID- 27381353 TI - Evaluation of Cerebral Hemodynamics and Tissue Morphology of In Vivo Rat Brain Using Spectral Diffuse Reflectance Imaging. AB - We investigated a quantitative imaging of reduced scattering coefficients MUs'( lambda) and the absorption coefficients MUa( lambda) of in vivo cortical tissues in the range from visible to near-infrared (NIR) wavelengths based on diffuse reflectance spectral imaging technique. In this method, diffuse reflectance images of in vivo cortical tissue are acquired at nine wavelengths (500, 520, 540, 560, 570, 580, 600, 730, and 760 nm). A multiple regression analysis aided by the Monte Carlo simulation for the absorbance spectra is then utilized to estimate the optical coefficients of cortical tissue. This analysis calculates the concentration of oxygenated hemoglobin and that of deoxygenated hemoglobin, the scattering amplitude a and the scattering power b. The spectrum of absorption coefficient is deduced from the estimated concentrations of oxygenated hemoglobin and deoxygenated hemoglobin. The spectrum of reduced scattering coefficient is determined by the estimated scattering amplitude and scattering power. The particle size distribution of microstructure is calculated from the estimated scattering power b for evaluating the morphological change in brain tissue quantitatively. Animal experiments with in vivo exposed brain of rats demonstrated that the responses of the absorption properties to hyperoxic and anoxic conditions are in agreement with the expected well-known cortical hemodynamics. The average particle size was significantly reduced immediately after the onset of anoxia and then it was changed into an increase, which implied the swelling and shrinkage of the cellular and subcellular structures induced by loss of tissue viability in brain tissue. PMID- 27381354 TI - Associations of self-reported height loss and kyphosis with vertebral fractures in Japanese women 60 years and older: a cross-sectional survey. AB - Some vertebral fractures come to clinical attention but most do not. This cross sectional survey aimed to clarify the associations of self-reported height loss and kyphosis with vertebral fractures. We enrolled 407 women aged 60-92 years who visited our orthopaedic clinic between June and August 2014 in our study. Inclusion criteria were lateral radiography followed by completion of a structured questionnaire in this study. The primary outcome was vertebral fracture diagnosed on lateral radiography and graded using a semiquantitative grading method, from SQ0 (normal) to SQ3 (severe). Self-reported kyphosis was defined as none, mild to moderate, severe. Self-reported height loss was defined as <4 cm or >=4 cm. Number of SQ1 fracture was associated only with kyphosis. Self-reported severe kyphosis was significantly associated with increased numbers of >=SQ2 vertebral fractures (p = 0.007). Height loss >=4 cm was significantly associated with increased >=SQ2 grade fractures (p < 0.001). Odds ratios (ORs) for fractures associated with mild-to-moderate and severe kyphosis were 2.1 [95% confidence interval 1.4 to 3.3) and 4.2 (1.8 to 9.5), respectively. OR for fractures associated with height loss >=4 cm was 2.3 (1.4 to 3.7). Self-reported kyphosis may be useful for identifying Japanese women aged >=60 years who have undetected vertebral fractures. PMID- 27381355 TI - Nutrient removal by Chlorella vulgaris F1068 under cetyltrimethyl ammonium bromide induced hormesis. AB - Toxicants are generally harmful to biotechnology in wastewater treatment. However, trace toxicant can induce microbial hormesis, but to date, it is still unknown how this phenomenon affects nutrient removal during municipal wastewater treatment process. Therefore, this study focused on the effects of hormesis induced by cetyltrimethyl ammonium bromide (CTAB), a representative quaternary ammonium cationic surfactant, on nutrient removal by Chlorella vulgaris F1068. Results showed that when the concentration of CTAB was less than 10 ng/L, the cellular components chlorophyll a, proteins, polysaccharides, and total lipids increased by 10.11, 58.17, 38.78, and 11.87 %, respectively, and some enzymes in nutrient metabolism of algal cells, such as glutamine synthetase (GS), acid phosphatase (ACP), H(+)-ATPase, and esterase, were also enhanced. As a result, the removal efficiencies of ammonia nitrogen (NH4 (+)) and total phosphorus (TP) increased by 14.66 and 8.51 %, respectively, compared to the control during a 7 day test period. The underlying mechanism was mainly due to an enhanced photosynthetic activity of C. vulgaris F1068 indicated by the increase in chlorophyll fluorescence parameters (the value of Fv/Fm, PhiII, Fv/Fo, and rETR increased by 12.99, 7.56, 25.59, and 8.11 %, respectively) and adenylate energy charge (AEC) (from 0.68 to 0.72). These results suggest that hormesis induced by trace toxicants could enhance the nutrient removal, which would be further considered in the design of municipal wastewater treatment processes. Graphical abstract The schematic mechanism of C. vulgaris F1068 under CTAB induced hormesis. Green arrows ( ) represent the increase and the red arrow ( ) represents the decrease. PMID- 27381356 TI - Comparison of PAHs uptake by selected Monocotyledones and Dicotyledones from municipal and industrial sewage sludge. AB - The study was focused on two goals: (i) the confirmation of the existence of a general relation between the content of polycyclic aromatic hydrocarbons (PAHs) in sewage sludge and in plants growing in it, regardless of the type and content of sewage sludge, and (ii) if so, the answer to the question whether the uptake of PAHs by plants depends on their type. To realize the set aims, the contents of PAHs in four differentiated plant species were measured, two belonging to the Monocotyledones and two belonging to Dicotyledones group, growing in municipal and industrial sewage sludge in two locations. All the investigations were carried out during the period of 3 years. The results clearly demonstrated that the uptake of PAHs by a plant depended on polyaromatic hydrocarbon concentration in the sewage sludge. The relation between accumulation coefficient of PAHs in plant material vs. the content of PAH in sewage sludge was of exponential character. The results indicate that in case of four- and five-ring PAHs, the root uptake mechanism from soil solution occurs, regardless of the type and origin of sewage sludge and the type of plant. For three-ring PAHs, we can assume for Monocotyledones that the root uptake mechanism occurs because we observe a significant correlation between the content of fluorene, phenanthrene, and anthracene in plant material and in the sewage sludge. For Dicotyledones, the correlation is insignificant, and in this case probably two mechanisms occur-the uptake by roots and by leaves. PMID- 27381357 TI - Effect of petroleum hydrocarbons in copper phytoremediation by a salt marsh plant (Juncus maritimus) and the role of autochthonous bioaugmentation. AB - This work aimed to investigate, under controlled but environmental relevant conditions, the effects of the presence of both inorganic and organic contaminants (copper and petroleum hydrocarbons) on phytoremediation potential of the salt marsh plant Juncus maritimus. Moreover, bioaugmentation, with an autochthonous microbial consortium (AMC) resistant to Cu, was tested, aiming an increase in the remediation potential of this plant in the presence of a co contamination. Salt marsh plants with sediment attached to their roots were collected, placed in vessels, and kept in greenhouses, under tidal simulation. Sediments were contaminated with Cu and petroleum, and the AMC was added to half of the vessels. After 5 months, plants accumulated significant amounts of Cu but only in belowground structures. The amount of Cu was even higher in the presence of petroleum. AMC addition increased Cu accumulation in belowground tissues, despite decreasing Cu bioavailability, promoting J. maritimus phytostabilization potential. Therefore, J. maritimus has potential to phytoremediate co contaminated sediments, and autochthonous bioaugmentation can be a valuable strategy for the recovery and management of moderately impacted estuaries. This approach can contribute for a sustainable use of the environmental resources. Graphical abstract ?. PMID- 27381358 TI - Microparticles: A new insight into lung primary graft dysfunction? AB - Lung transplantation is the only life-saving treatment for end stage respiratory disease. The immediate outcome is still hampered by primary graft dysfunction. The latter is a form of acute lung injury occurring within the 30min following the unclamping of the pulmonary artery that prompts ischemia reperfusion injury. Severe forms may need prolonged mechanical ventilation and extra-corporeal membrane oxygenation. Overall, primary graft dysfunction accounts for at least one third of the deaths during the first post-operative month. Despite increasing experience and knowledge on the underlying cellular events, there is still a lack of an early marker of ischemia reperfusion graft injuries. Microparticles are plasma membrane vesicles that are released from damaged or stressed cells in biological fluids and remodeling tissues, among which the lung parenchyma during acute or chronic injury. We recently evidenced alveolar microparticles as surrogate markers of strong ischemia injury in ex-vivo reperfusion experimental models. We propose herein new insights on how microparticles may be helpful to evaluate the extent of lung ischemia reperfusion injuries and predict the occurrence of primary graft dysfunction. PMID- 27381359 TI - Genetic profile of PTEN gene in Indian oral squamous cell carcinoma primary tumors. AB - BACKGROUND: Phosphatase and tensin homolog (PTEN) is the tumor suppressor gene located on chromosome10q23.3. Genetic variations in the PTEN gene have been found in various sporadic tumors. However, petite is known about the genetic profile of the PTEN gene in oral squamous cell carcinoma (OSCC), which is the eighth most common neoplasm worldwide and leading cancer in India. The purpose of the present study was to determine the frequency of genetic variations in the tyrosine phosphatase domain of the PTEN gene in an Indian OSCC subset. METHODS: We analyzed tyrosine phosphatase domain encoded by exon 5 of the PTEN gene in 59 OSCC primary tumors using PCR - direct genomic sequencing. RESULT: We observed one somatic deletion mutation, IVS4-30delT in three OSCC patients; two of them were at an advanced stage of carcinoma. Moreover, we identified one SNP rs 35560700(C>T), in five OSCC patients with the late stage of oral carcinoma. CONCLUSION: We identified 5% somatic mutational frequency in the intronic region of the tyrosine phosphatase domain of the PTEN gene; however, mutations were found absent in the coding region. Therefore, PTEN gene mutation is not a frequent event in the pathogenesis of OSCC in the targeted Indian cohort. PMID- 27381360 TI - Retrospective analysis of tigecycline shows that it may be an option for children with severe infections. AB - AIM: This study assessed the efficacy and safety of tigecycline in children with life-threatening infections. METHODS: We retrospectively reviewed the clinical records of patients treated with tigecycline from June 2012 to May 2014 in a Chinese tertiary centre. RESULTS: The study comprised 24 patients (14 male) with a median age of four years (range, 50 days-12 years). The most frequently isolated microorganism, most common isolation site and type of infection were Acinetobacter baumannii, tracheal aspirate fluid and ventilator-associated pneumonia, respectively. Tigecycline was administered at a loading dose of 1.5 or 2.0 mg/kg and 1.0 mg/kg every 12 hours after that. The average duration of treatment was 11.6 +/- 5.8 days. The clinical response and microbiological eradication rate were 37.5% and 29.2%, respectively. Six of the patients we studied (25.0%) died, and three of these deaths were considered to be infection related. Adverse drug reactions were identified in four patients (16.7%) during the treatment, including abnormal liver function, prolonged prothrombin time and diarrhoea. CONCLUSION: Our findings suggest that tigecycline may be an option for children with severe infections. However, more prospective, controlled trials are required to objectively evaluate the efficacy and safety of tigecycline in children. PMID- 27381361 TI - The first catalytic asymmetric cycloadditions of imines with an enolisable anhydride. AB - The first catalytic, asymmetric reactions of imines with homophthalic anhydride to form disubstituted 3,4-dihydroisoquinolones are reported. The use of N-mesyl aldimines is key, as more basic imines undergo rapid uncatalysed reactions, while imines possessing larger N-sulphonyl substituents form lactams with lower ee. PMID- 27381362 TI - Quantitative Study of Elasticity of Rabbit VX2 Liver Tumor with Alternated Cooling and Heating Treatment based on ARFI Ultrasound Imaging Technique. AB - Acoustic radiation force impulse (ARFI) ultrasound imaging technique is used to quantitatively evaluate the elasticity of rabbit VX2 liver tumor with alternated cooling and heating treatment (ACHT). ACHT was performed on fifteen VX2 liver tumor models established in fifteen male New Zealand white rabbits with open tumor plant. ARFI was performed on day 0, 1, 7 and 14 after ACHT and shear wave velocity (SWV) in ARFI was recorded to evaluate the elasticity of the treated area. The SWV value of the lesion on day 0, 1, 7 and 14 was 2.33 +/- 0.19 m/s, 3.09 +/- 0.40 m/s, 2.64 +/- 0.37 m/s and 2.26 +/- 0.24 m/s, respectively, indicating the treated areas get stiffer on day 1 and then get softer gradually by day. All the difference between adjacent time points was statistically significant. The SWV value of different parts on day 7 approved that the hardness of the treated area is heterogenous: the treated area in the center >the peripheral strip-shaped area >normal liver tissues, consistent with pathological changes. Meanwhile, ARFI combined with conventional US imaging can qualitatively and quantitatively exam the healing process of rabbit VX2 liver tumor after ACHT, and corresponds well to the pathological results. PMID- 27381363 TI - Testing gold nanostructures fabricated by hole-mask colloidal lithography as potential substrates for SERS sensors: sensitivity, signal variability, and the aspect of adsorbate deposition. AB - Gold nanoplasmonic substrates with high sensitivity and spectral reproducibility are key components of molecular sensors based on surface-enhanced Raman scattering (SERS). In this work, we used a confocal Raman microscope and several types of gold nanostructures (arrays of nanodiscs, nanocones and nanodisc dimers) prepared by hole-mask colloidal lithography (HCL) to determine the sources of variability in SERS measurements. We demonstrate that significant variations in the SERS signal can originate from the method of deposition of analyte molecules onto a SERS substrate. While the method based on incubation of SERS substrates in a solution containing the analyte yields a SERS signal with low variability, the droplet deposition method produces a SERS signal with rather high variability. Variability of the SERS signal of a single nanoparticle was determined from the statistical analysis of the SERS signal in short-range Raman maps recorded using different sized laser spots produced by means of different objectives. We show that the number of nanoparticles located within the laser spot can be a source of substantial SERS signal variability, especially for high-magnification objectives. We demonstrate that SERS substrates prepared by HCL exhibit high SERS enhancement and excellent homogeneity (about 20% relative standard deviation from short-range maps). The nanocone arrays are shown to provide the highest SERS enhancement, the lowest relative level of fluorescence background, and also slightly better homogeneity when compared with arrays of nanodisc dimers or single nanodiscs. PMID- 27381364 TI - Allometric equations for integrating remote sensing imagery into forest monitoring programmes. AB - Remote sensing is revolutionizing the way we study forests, and recent technological advances mean we are now able - for the first time - to identify and measure the crown dimensions of individual trees from airborne imagery. Yet to make full use of these data for quantifying forest carbon stocks and dynamics, a new generation of allometric tools which have tree height and crown size at their centre are needed. Here, we compile a global database of 108753 trees for which stem diameter, height and crown diameter have all been measured, including 2395 trees harvested to measure aboveground biomass. Using this database, we develop general allometric models for estimating both the diameter and aboveground biomass of trees from attributes which can be remotely sensed - specifically height and crown diameter. We show that tree height and crown diameter jointly quantify the aboveground biomass of individual trees and find that a single equation predicts stem diameter from these two variables across the world's forests. These new allometric models provide an intuitive way of integrating remote sensing imagery into large-scale forest monitoring programmes and will be of key importance for parameterizing the next generation of dynamic vegetation models. PMID- 27381365 TI - A Gestalt approach to Gram-negative entry. AB - A major obstacle confronting the discovery and development of new antibacterial agents to combat resistant Gram-negative (GN) organisms is the lack of a rational process for endowing compounds with properties that allow (or promote) entry into the bacterial cytoplasm. The major permeability difference between GN and Gram positive (GP) bacteria is the GN outer membrane (OM) which is a permeability barrier itself and potentiates efflux pumps that expel compounds. Based on the fact that OM-permeable and efflux-deleted GNs are sensitive to many anti-GP drugs, recent efforts to approach the GN entry problem have focused on ways of avoiding efflux and transiting or compromising the OM, with the tacit assumption that this could allow entry of compounds into the GN cytoplasm. But bypassing the OM and efflux obstacles does not take into account the additional requirement of penetrating the cytoplasmic membrane (CM) whose sieving properties appear to be orthogonal to that of the OM. That is, tailoring compounds to transit the OM may well compromise their ability to enter the cytoplasm. Thus, a Gestalt approach to understanding the chemical requirements for GN entry seems a useful adjunct. This might consist of characterizing compounds which reach the cytoplasm, grouping (or binning) by routes of entry and formulating chemical 'rules' for those bins. This will require acquisition of data on large numbers of compounds, using non activity-dependent methods of measuring accumulation in the cytoplasm. PMID- 27381367 TI - The principal pathways involved in the in vivo modulation of hypoxic pulmonary vasoconstriction, pulmonary arterial remodelling and pulmonary hypertension. AB - Hypoxic pulmonary vasoconstriction (HPV) serves to optimize ventilation-perfusion matching in focal hypoxia and thereby enhances pulmonary gas exchange. During global hypoxia, however, HPV induces general pulmonary vasoconstriction, which may lead to pulmonary hypertension (PH), impaired exercise capacity, right-heart failure and pulmonary oedema at high altitude. In chronic hypoxia, generalized HPV together with hypoxic pulmonary arterial remodelling, contribute to the development of PH. The present article reviews the principal pathways in the in vivo modulation of HPV, hypoxic pulmonary arterial remodelling and PH with primary focus on the endothelin-1, nitric oxide, cyclooxygenase and adenine nucleotide pathways. In summary, endothelin-1 and thromboxane A2 may enhance, whereas nitric oxide and prostacyclin may moderate, HPV as well as hypoxic pulmonary arterial remodelling and PH. The production of prostacyclin seems to be coupled primarily to cyclooxygenase-1 in acute hypoxia, but to cyclooxygenase-2 in chronic hypoxia. The potential role of adenine nucleotides in modulating HPV is unclear, but warrants further study. Additional modulators of the pulmonary vascular responses to hypoxia may include angiotensin II, histamine, serotonin/5 hydroxytryptamine, leukotrienes and epoxyeicosatrienoic acids. Drugs targeting these pathways may reduce acute and/or chronic hypoxic PH. Endothelin receptor antagonists and phosphodiesterase-5 inhibitors may additionally improve exercise capacity in hypoxia. Importantly, the modulation of the pulmonary vascular responses to hypoxia varies between species and individuals, with hypoxic duration and age. The review also define how drugs targeting the endothelin-1, nitric oxide, cyclooxygenase and adenine nucleotide pathways may improve pulmonary haemodynamics, but also impair pulmonary gas exchange by interference with HPV in chronic lung diseases. PMID- 27381366 TI - A novel strain of Bacteroides fragilis enhances phagocytosis and polarises M1 macrophages. AB - Commensal Bacteroides fragilis possesses immune-regulatory characteristics. Consequently, it has been proposed as a potential novel probiotic because of its therapeutic effects on immune imbalance, mental disorders and inflammatory diseases. Macrophages play a central role in the immune response, developing either a classical-M1 or an alternative-M2 phenotype after stimulation with various signals. The interactions between macrophages and B. fragilis, however, remain to be defined. Here, a new isolate of B. fragilis, ZY-312, was shown to possess admirable properties, including tolerance to simulated gastric fluid, intestinal fluid and ox bile, and good safety (MOI = 100, 200) and adherent ability (MOI = 100) to LoVo cells. Isolate ZY-312 cell lysate promoted phagocytosis of fluorescent microspheres and pathogenic bacteria in bone marrow derived macrophage (BMDM) cells. Gene expression of IL-12, iNOS and IL-1beta in BMDM cells was increased after treatment with ZY-312, indicating the induction of M1 macrophages, consistent with enhanced secretion of NO. Cell surface expression of CD80 and CD86 was also increased. This study is the first to demonstrate that B. fragilis enhances the phagocytic functions of macrophages, polarising them to an M1 phenotype. Our findings provide insight into the close relationship between B. fragilis and the innate immune system. PMID- 27381368 TI - Comparative analyses across cattle genders and breeds reveal the pitfalls caused by false positive and lineage-differential copy number variations. AB - We compared CNV region (CNVR) results derived from 1,682 Nellore cattle with equivalent results derived from our previous analysis of Bovine HapMap samples. By comparing CNV segment frequencies between different genders and groups, we identified 9 frequent, false positive CNVRs with a total length of 0.8 Mbp that were likely caused by assembly errors. Although there was a paucity of lineage specific events, we did find one 54 kb deletion on chr5 significantly enriched in Nellore cattle. A few highly frequent CNVRs present in both datasets were detected within genomic regions containing olfactory receptor, ATP-binding cassette, and major histocompatibility complex genes. We further evaluated their impacts on downstream bioinformatics and CNV association analyses. Our results revealed pitfalls caused by false positive and lineage-differential copy number variations and will increase the accuracy of future CNV studies in both taurine and indicine cattle. PMID- 27381369 TI - The Na+/Glucose Cotransporter Inhibitor Canagliflozin Activates AMPK by Inhibiting Mitochondrial Function and Increasing Cellular AMP Levels. AB - Canagliflozin, dapagliflozin, and empagliflozin, all recently approved for treatment of type 2 diabetes, were derived from the natural product phlorizin. They reduce hyperglycemia by inhibiting glucose reuptake by sodium/glucose cotransporter (SGLT) 2 in the kidney, without affecting intestinal glucose uptake by SGLT1. We now report that canagliflozin also activates AMPK, an effect also seen with phloretin (the aglycone breakdown product of phlorizin), but not to any significant extent with dapagliflozin, empagliflozin, or phlorizin. AMPK activation occurred at canagliflozin concentrations measured in human plasma in clinical trials and was caused by inhibition of Complex I of the respiratory chain, leading to increases in cellular AMP or ADP. Although canagliflozin also inhibited cellular glucose uptake independently of SGLT2, this did not account for AMPK activation. Canagliflozin also inhibited lipid synthesis, an effect that was absent in AMPK knockout cells and that required phosphorylation of acetyl-CoA carboxylase (ACC) 1 and/or ACC2 at the AMPK sites. Oral administration of canagliflozin activated AMPK in mouse liver, although not in muscle, adipose tissue, or spleen. Because phosphorylation of ACC by AMPK is known to lower liver lipid content, these data suggest a potential additional benefit of canagliflozin therapy compared with other SGLT2 inhibitors. PMID- 27381370 TI - Fat Mass Reduction With Adipocyte Hypertrophy and Insulin Resistance in Heterozygous PPARgamma Mutant Rats. AB - Agonist-induced activation of peroxisome proliferator-activated receptor-gamma (PPARgamma) stimulates adipocyte differentiation and insulin sensitivity. Patients with heterozygous PPARgamma dominant-negative mutation develop partial lipodystrophy and insulin resistance. Inconsistent with this evidence in humans, it was reported that heterozygous PPARgamma knockout mice have increased insulin sensitivity and that mice with heterozygous PPARgamma dominant-negative mutation have normal insulin sensitivity and improved glucose tolerance. In the context of the interspecies intranslatability of PPARgamma-related findings, we generated a PPARgamma mutant rat with a loss-of-function mutation (Pparg(mkyo)) without dominant-negative activity by using the ENU (N-ethyl-N-nitrosourea) mutagenesis method. Heterozygous Pparg(mkyo/+) rats showed reduced fat mass with adipocyte hypertrophy and insulin resistance, which were highly predictable from known actions of PPARgamma agonists and phenotypes of patients with the PPARgamma mutation. This report is the first in our knowledge to clearly demonstrate that both alleles of PPARgamma are required for normal adipocyte development and insulin sensitivity in vivo. Furthermore, the study indicates that PPARgamma regulates mainly adipocyte number rather than adipocyte size in vivo. The choice of appropriate species as experimental models is critical, especially for the study of PPARgamma. PMID- 27381371 TI - Divergent functional profiles of acidic and basic phospholipases A2 in the venom of the snake Porthidium lansbergii lansbergii. AB - The Lansberg's hognose pitviper, Porthidium lansbergii lansbergii, inhabits northern Colombia. A recent proteomic characterization of its venom (J. Proteomics [2015] 114, 287-299) revealed the presence of phospholipases A2 (PLA2) accounting for 16.2% of its proteins. The two most abundant PLA2s were biochemically and functionally characterized. Pllans-I is a basic, dimeric enzyme with a monomer mass of 14,136 Da, while Pllans-II is an acidic, monomeric enzyme of 13,901 Da. Both have Asp49 in their partial amino acid sequences and, accordingly, are catalytically active upon natural or synthetic substrates. Nevertheless, these two enzymes differ markedly in their bioactivities. Pllans-I induces myonecrosis, edema, and is lethal by intracerebro-ventricular injection in mice, as well as cytolytic and anticoagulant in vitro. In contrast, Pllans-II is devoid of these effects, except for the induction of a moderate edema. In spite of lacking myotoxicity, Pllans-II enhances the muscle damaging action of Pllans-I in vivo. Altogether, results further illustrate the divergent functional profiles of basic and acidic PLA2s in viperid venoms, and suggest that Pllans-I plays a myotoxic role in envenomings by P. l. lansbergii, whereas Pllans-II, apparently devoid of toxicity, enhances muscle damage caused by Pllans-I. PMID- 27381372 TI - Plate Positioning in Periprosthetic or Interprosthetic Femur Fractures With Stable Implants-A Biomechanical Study. AB - BACKGROUND: Angular stable plate fixation is a widely accepted treatment option for interprosthetic or periprosthetic femoral fractures with stable implants. This biomechanical study tries to establish a safe distance of the plate from the tip of a femoral prosthesis. METHODS: A total of 38 composite femurs were reamed to an inner diameter of 23 mm to create an osteoporotic bone model. A Weber hip stem was cemented into each and a distal femoral NCB plate applied with the distance to the stem varying from 8 cm apart to 6 cm overlap in 2-cm steps. Each specimen was tested in cyclic axial loading (400 N-1500 N) and then cyclic torsion (0.6 Nm-50 Nm). Peak strain on the femur around the tip of the plate was measured with a 3D image correlation system and averaged over 26 cycles (excluding the first 3 and the last cycles). Finally, each femur was axially loaded to failure. RESULTS: Strain increased with decreasing overlap or gap. Seven specimens failed early between 2-cm overlap and 2-cm gap. Results were divided into a far group with a distance of >4 cm and a close group of <4 cm. Strain was significantly higher in the close group for axial (P < .001) and torsional (P < .001) loading. Failure load was significantly lower in the close group (P = .002). CONCLUSION: A minimal gap and/or overlap of at least 6 cm is recommended in osteoporotic bone to avoid stress risers. PMID- 27381373 TI - Incidence of and Preoperative Risk Factors for Surgical Delay in Primary Total Hip Arthroplasty: Analysis From the American College of Surgeons National Surgical Quality Improvement Program. AB - BACKGROUND: Total joint arthroplasty is a proven treatment for osteoarthritis of the knee and hip that has failed conservative treatment. While most of total joint arthroplasty is considered elective with surgery on the day of admission, a small subset of patients may require delay in surgery past the day of admission. Recently, surgical delay for primary total knee arthroplasty has been identified. However, the incidence, outcomes, and risk factors for delay in surgery before total hip arthroplasty (THA) have not been previously defined. QUESTIONS/PURPOSE: In patients undergoing THA, we sought to define (1) the incidence of and risk factors for delay in surgery, (2) the postoperative complications between surgical delay and no surgical delay cohorts, and (3) association of the Charlson comorbidity index (CCI) in patients with delay of surgery. METHODS: We retrospectively queried the National Surgical Quality Improvement Program database using Current Procedural Terminology billing codes and identified 7890 THAs performed between 2006 and 2010. Univariate and subsequent multivariate logistic regression analysis were then used to identify risk factors for surgical delay. Correlation between CCI and surgical delay in THA was evaluated. RESULTS: One-hundred seventy-nine patients (2.31%) were identified as experiencing a surgical delay before THA. Multivariate analysis identified congestive heart failure (CHF) (P = .0038), bleeding disorder (P < .0001), sepsis (P < .0001), prior operation in past 30 days (P = .0001), dependent functional status (P < .0001), American Society of Anesthesiologists class 3 (P = .0001), American Society of Anesthesiologists class 4 (P = .0023), significant weight loss (P = .0109), and hematocrit <38% (P < .0001) as independent risk factors for delay in surgery. Compared with the nondelay cohort, those experiencing surgical delay before THA had higher rates of postoperative surgical (8.9% vs 3.1%, P < .0001) and medical complications (23.5% vs 10.1%, P < .0001). Mean CCI was higher in the THA surgical delay cohort (3.16 vs 2.24, P < .0001) compared with the nondelay group. CONCLUSION: Surgical delay in patients undergoing THA may cause undue disruption in surgeon and hospital resource utilization. In an era of quality assessment and cost consciousness, it is important to understand that the short term outcomes of elective, same day THA differ dramatically from those hospitalized for medical necessity before surgery. Surgeons should consider thorough medical evaluation in those with CHF, bleeding disorders, sepsis, significant weight loss, and hematocrit <38% before hospital admission. PMID- 27381374 TI - Canonical Wnt/beta-Catenin Signaling Pathway Is Dysregulated in Patients With Primary and Secondary Myelofibrosis. AB - INTRODUCTION: beta-Catenin is a central effector molecule of the canonical wingless-related integration site (Wnt) signaling pathway. It is important for maintenance of stem cell homeostasis and its aberrant activation has been implicated in a wide array of malignant hematological disorders. There are few reports suggesting its dysregulation in Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs). PATIENTS AND METHODS: We analyzed beta catenin mRNA expression in bone marrow (BM) aspirates of 29 patients with primary (PMF) and 4 patients with secondary, post Ph- MPN, myelofibrosis (SMF) using quantitative real-time polymerase chain reaction (qRT PCR). The control group consisted of 16 BM aspirates from patients with limited-stage aggressive non Hodgkin lymphoma without BM involvement. We compared relative gene expression with clinical and hematological parameters. RESULTS: Relative expression of beta catenin differed significantly among groups (P = .0002), it was significantly higher in patients with PMF and SMF than in the control group, but did not differ between patients with PMF and SMF. A negative correlation was found regarding hemoglobin level in PMF (P = .017). No association according to Janus kinase 2 (JAK2) V617F mutational status or JAK2 V617F allele burden was detected. CONCLUSION: Our results show for the first time that beta-catenin mRNA expression is increased in patients with PMF and SMF and its upregulation might potentiate anemia. A number of inflammatory cytokines associated with PMF are capable of mediating their effects through increased beta-catenin expression. Accordingly, beta-catenin can induce expression of a number of genes implicated in processes of cell cycle control, fibrosis, and angiogenesis, which are central to the PMF pathogenesis. Therefore, beta-catenin might represent an interesting new therapeutic target in these diseases. PMID- 27381375 TI - International Committee on Systematics of Prokaryotes Subcommittee on the taxonomy of Halobacteriaceae. Minutes of the closed meeting, 23 May 2016, San Juan, Puerto Rico. PMID- 27381376 TI - Presence of alcoholic steatohepatitis, but no selective histological feature, indicates an increased risk of cirrhosis and premature death. AB - OBJECTIVE: The prognostic impact of early stages of histologically confirmed alcoholic liver disease is uncertain. Our aim was to determine the risk of cirrhosis and premature death, and identify prognostic markers, in patients with biopsy-proven alcoholic steatohepatitis - and to compare prognosis in patients with alcoholic pure fatty liver and the general population. MATERIAL AND METHODS: Patients with biopsy-proven alcoholic fatty liver disease diagnosed during 1976 1987 were identified. Data were collected from medical records, the Danish National Patient Registry and the Registry of Causes of Death. All biopsies were re-examined and morphological findings assessed. A reference cohort matched for age and gender was created. Cox proportional hazard models adjusted for age and gender were used to analyse differences in mortality and cirrhosis development, as well as the prognostic impact of histological and biochemical parameters. RESULTS: Two hundred and twenty-five patients with fatty liver and 111 with steatohepatitis were followed for median 13 and 9.7 years, respectively. There was a significantly higher risk of developing cirrhosis amongst patients with steatohepatitis compared to both patients with fatty liver (p < 0.001) and the reference cohort (p < 0.001). Mortality was significantly higher in patients with steatohepatitis compared to patients with fatty liver (p = 0.046) and the general population (p < 0.001). No histological or biochemical parameters with prognostic significance for mortality were identified. CONCLUSION: Presence of steatohepatitis indicates an increased risk of cirrhosis and premature death. However, none of the histological parameters defining steatohepatitis can independently identify patients at risk for premature death. PMID- 27381377 TI - Comment on the recent ILAE special report on the definition and classification of status epilepticus. PMID- 27381378 TI - Erratum. PMID- 27381379 TI - Post-acute Care Trajectories in the First Year Following Hospital Discharge After Left Ventricular Assist Device Implantation. AB - INTRODUCTION: Patients with advanced heart failure who undergo left ventricular assist device (LVAD) implantation are heavy users of post-acute care services. We sought to better describe the post-acute trajectories and burden of care transitions for this patient population. METHODS AND RESULTS: We conducted a retrospective cohort study of 227 patients who were discharged after index hospitalization for LVAD implantation. Of these, 162 (71%) were discharged home, and 65 (29%) were discharged to a facility, including long-term acute care hospitals (n = 50), inpatient rehabilitation facilities (n = 11), and skilled nursing facilities (n = 4). Follow-up extended to 1 year, with censoring at date of heart transplantation, LVAD removal, death, or loss of follow- up. In the first year post-discharge, those patients initially discharged home spent a mean 265 days at home, 0.5 days in a facility, and 13 days in the hospital as result of readmission. Those initially discharged to a facility spent a mean 241 days at home, 37 days in a facility, and 19 days in the hospital as result of readmission. Patients initially discharged home experienced fewer care transitions, 4.2 vs 5.2 transitions per patient, compared with those initially discharged to a facility. CONCLUSIONS: In the first year following index hospitalization for LVAD implantation, patients initially discharged to a facility have an increased burden of care transitions, as well as time spent in the hospital and in a facility, compared with patients initially discharged home. Specialized models of care are needed in facilities caring for patients with LVADs. PMID- 27381380 TI - Evaluation of dental therapists undertaking dental examinations in a school setting in Scotland. AB - OBJECTIVE: To measure agreement between dental therapists and the Scottish gold standard dentist undertaking National Dental Inspection Programme (NDIP) examinations. METHODS: A study of interexaminer agreement between 19 dental therapists and the national gold-standard dentist was carried out. Pre calibration training used the caries diagnostic criteria and examination techniques agreed by the British Association for the Study of Community Dentistry (BASCD). Twenty-three 5-year-old children (Primary 1) and 17 11-year-old children (Primary 7) children were examined. Agreement was assessed using kappa statistics on d3 mft and D3 MFT for P1 and P7 children, sensitivity and specificity values, and kappa statistics on d3 t/D3 T and ft/FT. Calibration data on P1 and P7 children from 2009-2012 involving dentists as examiners were used for comparison. Economic evaluation was undertaken using a cost minimization analysis approach. RESULTS: The mean kappa score was 0.84 (SD 0.07) ranging from 0.69 to 0.94. All dental therapists scored good or very good agreement with the gold-standard dentist. This compares with historic NDIP calibration data with dentists, against the same gold-standard dentist, where the mean kappa value was 0.68 (SD 0.22) with a range of 0.35-1.00. The mean sensitivity score was 0.98 (SD 0.04) (range 0.88-1.0) and mean specificity score was 0.90 (SD 0.06) (range 0.78-0.96). Health economic analysis estimated that salary costs would be 33.6% lower if dental therapists were substituted for dentists in the year 2013, with an estimated saving of approximately L103 646 per annum on the national budget. CONCLUSION: We conclude that dental therapists show a high level of interexaminer agreement, and with the appropriate annual training and calibration, they could undertake dental examinations as part of the NDIP programme. PMID- 27381381 TI - Hierarchical Nanocomposite of Hollow N-Doped Carbon Spheres Decorated with Ultrathin WS2 Nanosheets for High-Performance Lithium-Ion Battery Anode. AB - Hierarchical nanocomposite of ultrathin WS2 nanosheets uniformly attached on the surface of hollow nitrogen-doped carbon spheres (WS2@HNCSs) were successfully fabricated via a facile synthesis strategy. When evaluated as an anode material for LIBs, the hierarchical WS2@HNCSs exhibit a high specific capacity of 801.4 mA h g(-1) at 0.1 A g(-1), excellent rate capability (545.6 mA h g(-1) at a high current density of 2 A g(-1)), and great cycling stability with a capacity retention of 95.8% after 150 cycles at 0.5 A g(-1). The Li-ion storage properties of our WS2@HNCSs nanocomposite are much better than those of the previously most reported WS2-based anode materials. The impressive electrochemical performance is attributed to the robust nanostructure and the favorable synergistic effect between the ultrathin (3-5 layers) WS2 nanosheets and the highly conductive hollow N-doped carbon spheres. The hierarchical hybrid can simultaneously facilitate fast electron/ion transfer, effectively accommodate mechanical stress from cycling, restrain agglomeration, and enable full utilization of the active materials. These characteristics make WS2@HNCSs a promising anode material for high-performance LIBs. PMID- 27381382 TI - Unstable tandem gene amplification generates heteroresistance (variation in resistance within a population) to colistin in Salmonella enterica. AB - Heteroresistance, a phenomenon where subpopulations of a bacterial isolate exhibit different susceptibilities to an antibiotic, is a growing clinical problem where the underlying genetic mechanisms in most cases remain unknown. We isolated colistin resistant mutants in Escherichia coli and Salmonella enterica serovar Typhimurium at different concentrations of colistin. Genetic analysis showed that genetically stable pmrAB point mutations were responsible for colistin resistance during selection at high drug concentrations for both species and at low concentrations for E. coli. In contrast, for S. Typhimurium mutants selected at low colistin concentrations, amplification of different large chromosomal regions conferred a heteroresistant phenotype. All amplifications included the pmrD gene, which encodes a positive regulator that up-regulates proteins that modify lipid A, and as a result increase colistin resistance. Inactivation and over-expression of the pmrD gene prevented and conferred resistance, respectively, demonstrating that the PmrD protein is required and sufficient to confer resistance. The heteroresistance phenotype is explained by the variable gene dosage of pmrD in a population, where sub-populations with different copy number of the pmrD gene show different levels of colistin resistance. We propose that variability in gene copy number of resistance genes can explain the heteroresistance observed in clinically isolated pathogenic bacteria. PMID- 27381383 TI - Fast measurement of the quadriceps femoris muscle transverse relaxation time at high magnetic field using segmented echo-planar imaging. AB - PURPOSE: To assess and validate a technique for transverse relaxation time (T2 ) measurements of resting and recovering skeletal muscle following exercise with a high temporal resolution and large volume coverage using segmented spin-echo echo planar imaging (sSE-EPI). MATERIALS AND METHODS: Experiments were performed on a 3T magnetic resonance imaging (MRI) scanner using a multislice sSE-EPI technique applied at different echo times (TEs). T2 measurements were first validated in vitro in calibrated T2 phantoms (range: 25-152 ms) by comparing sSE-EPI, standard spin-echo (SE), and multislice multiecho (MSME) techniques (using a fitting procedure or a 2-TEs calculation). In vivo measurements of resting T2 quadriceps femoris (QF) muscle were performed with both sSE-EPI and MSME sequences. Finally, sSE-EPI was used to quantify T2 changes in recovering muscle after an exercise. RESULTS: T2 values measured in vitro with sSE-EPI were similar to those assessed with SE (P > 0.05). In vitro and in vivo T2 measurements obtained with sSE-EPI were independent of the T2 determination procedure (P > 0.05). In contrast, both in vitro and in vivo T2 values derived from MSME were significantly different when using 2-TEs calculation as compared to the fitting procedure (P < 0.05). sSE EPI allowed the detection of increased T2 values in the QF muscle immediately after exercise (+14 +/- 9%), while lower T2 values were recorded less than 2 min afterwards (P < 0.05). CONCLUSION: sSE-EPI sequence is a relevant method to monitor exercise-induced T2 changes of skeletal muscles over large volume coverage and to detect abnormal patterns of muscle activation. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:356-368. PMID- 27381384 TI - Current Topics in Postnatal Behavioral Testing. AB - The study of developmental neurotoxicity (DNT) continues to be an important component of safety evaluation of candidate therapeutic agents and of industrial and environmental chemicals. Developmental neurotoxicity is considered to be an adverse change in the central and/or peripheral nervous system during development of an organism and has been primarily evaluated by studying functional outcomes, such as changes in behavior, neuropathology, neurochemistry, and/or neurophysiology. Neurobehavioral evaluations are a component of a wide range of toxicology studies in laboratory animal models, whereas neurochemistry and neurophysiology are less commonly employed. Although the primary focus of this article is on neurobehavioral evaluation in pre- and postnatal development and juvenile toxicology studies used in pharmaceutical development, concepts may also apply to adult nonclinical safety studies and Environmental Protection Agency/chemical assessments. This article summarizes the proceedings of a symposium held during the 2015 American College of Toxicology annual meeting and includes a discussion of the current status of DNT testing as well as potential issues and recommendations. Topics include the regulatory context for DNT testing; study design and interpretation; behavioral test selection, including a comparison of core learning and memory systems; age of testing; repeated testing of the same animals; use of alternative animal models; impact of findings; and extrapolation of animal results to humans. Integration of the regulatory experience and scientific concepts presented during this symposium, as well as from subsequent discussion and input, provides a synopsis of the current state of DNT testing in safety assessment, as well as a potential roadmap for future advancement. PMID- 27381385 TI - Safe and Sensitive Antiviral Screening Platform Based on Recombinant Human Coronavirus OC43 Expressing the Luciferase Reporter Gene. AB - Human coronaviruses (HCoVs) cause 15 to 30% of mild upper respiratory tract infections. However, no specific antiviral drugs are available to prevent or treat HCoV infections to date. Here, we developed four infectious recombinant HCoVs-OC43 (rHCoVs-OC43) which express the Renilla luciferase (Rluc) reporter gene. Among these four rHCoVs-OC43, rOC43-ns2DelRluc (generated by replacing ns2 with the Rluc gene) showed robust luciferase activity with only a slight impact on its growth characteristics. Additionally, this recombinant virus remained stable for at least 10 passages in BHK-21 cells. rOC43-ns2DelRluc was comparable to its parental wild-type virus (HCoV-OC43-WT) with respect to the quantity of the antiviral activity of chloroquine and ribavirin. We showed that chloroquine strongly inhibited HCoV-OC43 replication in vitro, with a 50% inhibitory concentration (IC50) of 0.33 MUM. However, ribavirin showed inhibition of HCoV OC43 replication only at high concentrations which may not be applicable to humans in clinical treatment, with an IC50 of 10 MUM. Furthermore, using a luciferase-based small interfering RNA (siRNA) screening assay, we identified double-stranded-RNA-activated protein kinase (PKR) and DEAD box RNA helicases (DDX3X) that exhibited antiviral activities, which were further verified by the use of HCoV-OC43-WT. Therefore, rOC43-ns2DelRluc represents a promising safe and sensitive platform for high-throughput antiviral screening and quantitative analysis of viral replication. PMID- 27381386 TI - Effect of the beta-Lactamase Inhibitor Vaborbactam Combined with Meropenem against Serine Carbapenemase-Producing Enterobacteriaceae. AB - Klebsiella pneumoniae carbapenemase (KPC)-producing isolates have become increasingly prevalent worldwide, and these organisms are often multidrug resistant, limiting the therapeutic options available for treating infections. We evaluated the activity of meropenem combined with the serine beta-lactamase inhibitor vaborbactam (formerly RPX7009) against 315 serine carbapenemase producing Enterobacteriaceae (CPE) isolates by use of checkerboard-designed panels to assess the optimal inhibitor concentration (range tested, 0.5 to 32 MUg/ml). Overall, meropenem alone (MIC50 and MIC90, 16 and >64 MUg/ml, respectively) inhibited only 2.2% of the isolates at <=1 MUg/ml (the CLSI susceptibility breakpoint) and 7.3% of the isolates at <=2 MUg/ml (the EUCAST breakpoint). Vaborbactam restored meropenem activity for 72.7 to 98.1% of CPE isolates at <=2 MUg/ml, and maximum potentiation was achieved with fixed concentrations of >=8 MUg/ml of the inhibitor (>=96.5% of isolates were inhibited at <=2 MUg/ml of meropenem-vaborbactam). Meropenem-vaborbactam with a fixed concentration of 8 MUg/ml of the inhibitor (MIC50, <=0.06 MUg/ml for all organisms) inhibited 93.7% of the CPE isolates displaying elevated meropenem MICs at <=1 MUg/ml. Meropenem-vaborbactam MICs were elevated for isolates producing metallo-beta-lactamases (MIC, 16 to >64 MUg/ml) or displaying decreased expression of OmpK37 and/or elevated expression of the AcrAB-TolC efflux system (MIC, 16 MUg/ml). Vaborbactam showed no antibacterial activity alone (all MICs, >64 MUg/ml). Meropenem-vaborbactam appears to be a good candidate for further development and it could increase the options for treatment of serious infections caused by carbapenemase-producing pathogens. PMID- 27381387 TI - The Heterodimeric ABC Transporter EfrCD Mediates Multidrug Efflux in Enterococcus faecalis. AB - Nosocomial infections with Enterococcus faecalis are an emerging health problem. However, drug efflux pumps contributing to intrinsic drug resistance are poorly studied in this Gram-positive pathogen. In this study, we functionally investigated seven heterodimeric ABC transporters of E. faecalis that are annotated as drug efflux pumps. Deletion of ef0789-ef0790 on the chromosome of E. faecalis resulted in increased susceptibility to daunorubicin, doxorubicin, ethidium, and Hoechst 33342, and the corresponding transporter was named EfrCD. Unexpectedly, the previously described heterodimeric multidrug ABC transporter EfrAB contributes marginally to drug efflux in the endogenous context of E. faecalis In contrast, heterologous expression in Lactococcus lactis revealed that EfrAB, EfrCD, and the product of ef2226-ef2227 (EfrEF) mediate the efflux of fluorescent substrates and confer resistance to multiple dyes and drugs, including fluoroquinolones. Four of seven transporters failed to exhibit drug efflux activity for the set of drugs and dyes tested, even upon overexpression in L. lactis Since all seven transporters were purified as heterodimers after overexpression in L. lactis, a lack of drug efflux activity is not attributed to poor expression or protein aggregation. Reconstitution of the purified multidrug transporters EfrAB, EfrCD, and EfrEF in proteoliposomes revealed functional coupling between ATP hydrolysis and drug binding. Our analysis creates an experimental basis for the accurate prediction of drug efflux transporters and indicates that many annotated multidrug efflux pumps might be incapable of drug transport and thus might fulfill other physiological functions in the cell. PMID- 27381388 TI - VIM-2-Producing Pseudomonas spp. in Uruguay: Sequence Types, Pulsotypes, and Class 1 Integrons Including New Variable Regions Featuring blaVIM-2 and blaGES-7. PMID- 27381389 TI - Rifamycin Resistance in Clostridium difficile Is Generally Associated with a Low Fitness Burden. AB - We characterized clinically occurring and novel mutations in the beta subunit of RNA polymerase in Clostridium difficile (CdRpoB), conferring rifamycin (including rifaximin) resistance. The Arg505Lys substitution did not impose an in vitro fitness cost, which may be one reason for its dominance among rifamycin-resistant clinical isolates. These observations were supported through the structural modeling of CdRpoB. In general, most mutations lacked in vitro fitness costs, suggesting that rifamycin resistance may in some cases persist in the clinic. PMID- 27381390 TI - Whole-Genome Sequencing for Detecting Antimicrobial Resistance in Nontyphoidal Salmonella. AB - Laboratory-based in vitro antimicrobial susceptibility testing is the foundation for guiding anti-infective therapy and monitoring antimicrobial resistance trends. We used whole-genome sequencing (WGS) technology to identify known antimicrobial resistance determinants among strains of nontyphoidal Salmonella and correlated these with susceptibility phenotypes to evaluate the utility of WGS for antimicrobial resistance surveillance. Six hundred forty Salmonella of 43 different serotypes were selected from among retail meat and human clinical isolates that were tested for susceptibility to 14 antimicrobials using broth microdilution. The MIC for each drug was used to categorize isolates as susceptible or resistant based on Clinical and Laboratory Standards Institute clinical breakpoints or National Antimicrobial Resistance Monitoring System (NARMS) consensus interpretive criteria. Each isolate was subjected to whole genome shotgun sequencing, and resistance genes were identified from assembled sequences. A total of 65 unique resistance genes, plus mutations in two structural resistance loci, were identified. There were more unique resistance genes (n = 59) in the 104 human isolates than in the 536 retail meat isolates (n = 36). Overall, resistance genotypes and phenotypes correlated in 99.0% of cases. Correlations approached 100% for most classes of antibiotics but were lower for aminoglycosides and beta-lactams. We report the first finding of extended spectrum beta-lactamases (ESBLs) (blaCTX-M1 and blaSHV2a) in retail meat isolates of Salmonella in the United States. Whole-genome sequencing is an effective tool for predicting antibiotic resistance in nontyphoidal Salmonella, although the use of more appropriate surveillance breakpoints and increased knowledge of new resistance alleles will further improve correlations. PMID- 27381391 TI - The Role of Signaling via Aqueous Pore Formation in Resistance Responses to Amphotericin B. AB - Drug resistance studies have played an important role in the validation of antibiotic targets. In the case of the polyene antibiotic amphotericin B (AmB), such studies have demonstrated the essential role that depletion of ergosterol plays in the development of AmB-resistant (AmB-R) organisms. However, AmB-R strains also occur in fungi and parasitic protozoa that maintain a normal level of ergosterol at the plasma membrane. Here, I review evidence that shows not only that there is increased protection against the deleterious consequences of AmB induced ion leakage across the membrane in these resistant pathogens but also that a set of events are activated that block the cell signaling responses that trigger the oxidative damage produced by the antibiotic. Such signaling events appear to be the consequence of a membrane-thinning effect that is exerted upon lipid-anchored Ras proteins by the aqueous pores formed by AmB. A similar membrane disturbance effect may also explain the activity of AmB on mammalian cells containing Toll-like receptors. These resistance mechanisms expand our current understanding of the role that the formation of AmB aqueous pores plays in triggering signal transduction responses in both pathogens and host immune cells. PMID- 27381392 TI - Two Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending-Dose Studies To Investigate the Safety, Tolerability, and Pharmacokinetics of an Anti Influenza A Virus Monoclonal Antibody, MHAA4549A, in Healthy Volunteers. AB - Hospitalized patients with severe influenza are at significant risk for morbidity and mortality. MHAA4549A is a human monoclonal immunoglobulin (Ig) G1 antibody that binds to a highly conserved stalk region of the influenza A virus hemagglutinin protein and neutralizes all tested seasonal human influenza A virus strains. Two phase 1 trials examined the safety, tolerability, and pharmacokinetics of MHAA4549A in healthy volunteers. Both single ascending-dose trials were randomized, double blinded, and placebo controlled. Trial 1 randomized 21 healthy adults into four cohorts receiving a single intravenous dose of 1.5, 5, 15, or 45 mg/kg MHAA4549A or placebo. Trial 2 randomized 14 healthy adults into two cohorts receiving a single intravenous fixed dose of 8,400 mg or 10,800 mg of MHAA4549A or placebo. Subjects were followed for 120 days after dosing. No subject was discontinued in either trial, and no serious adverse events were reported. The most common adverse event in both studies was mild headache (trial 1, 4/16 subjects receiving MHAA4549A and 1/5 receiving placebo; trial 2, 4/8 subjects receiving MHAA4549A and 2/6 receiving placebo). MHAA4549A produced no relevant time- or dose-related changes in laboratory values or vital signs compared to those with placebo. No subjects developed an antitherapeutic antibody response following MHAA4549A administration. MHAA4549A showed linear serum pharmacokinetics, with a mean half-life of 22.5 to 23.7 days. MHAA4549A is safe and well tolerated in healthy volunteers up to a single intravenous dose of 10,800 mg and demonstrates linear serum pharmacokinetics consistent with those of a human IgG1 antibody lacking known endogenous targets in humans. (These trials have been registered at ClinicalTrials.gov under registration no. NCT01877785 and NCT02284607). PMID- 27381393 TI - In Vitro Exposure to PC-1005 and Cervicovaginal Lavage Fluid from Women Vaginally Administered PC-1005 Inhibits HIV-1 and HSV-2 Infection in Human Cervical Mucosa. AB - Our recent phase 1 trial demonstrated that PC-1005 gel containing 50 MUM MIV-150, 14 mM zinc acetate dihydrate, and carrageenan (CG) applied daily vaginally for 14 days is safe and well tolerated. Importantly, cervicovaginal lavage fluid samples (CVLs) collected 4 or 24 h after the last gel application inhibited HIV-1 and human papillomavirus (HPV) in cell-based assays in a dose-dependent manner (MIV 150 for HIV-1 and CG for HPV). Herein we aimed to determine the anti-HIV and anti herpes simplex virus 2 (anti-HSV-2) activity of PC-1005 in human cervical explants after in vitro exposure to the gel and to CVLs from participants in the phase 1 trial. Single HIV-1BaL infection and HIV-1BaL-HSV-2 coinfection explant models were utilized. Coinfection with HSV-2 enhanced tissue HIV-1BaL infection. In vitro exposure to PC-1005 protected cervical mucosa against HIV-1BaL (up to a 1:300 dilution) in single-challenge and cochallenge models. CG gel (PC-525) provided some barrier effect against HIV-1BaL at the 1:100 dilution in a single challenge model but not in the cochallenge model. Both PC-1005 and PC-525 at the 1:100 dilution inhibited HSV-2 infection, pointing to a CG-mediated protection. MIV-150 and CG in CVLs inhibited HIV (single-challenge or cochallenge models) and HSV-2 infections in explants in a dose-dependent manner (P < 0.05). Stronger inhibition of HIV-1 infection by CVLs collected 4 h after the last gel administration was observed compared to infection detected in the presence of baseline CVLs. The anti-HIV and anti-HSV-2 activity of PC-1005 gel in vitro and CVLs in human ectocervical explants supports the further development of PC-1005 gel as a broad-spectrum on-demand microbicide. PMID- 27381394 TI - The Lantibiotic NAI-107 Efficiently Rescues Drosophila melanogaster from Infection with Methicillin-Resistant Staphylococcus aureus USA300. AB - We used the fruit fly Drosophila melanogaster as a cost-effective in vivo model to evaluate the efficacy of novel antibacterial peptides and peptoids for treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. A panel of peptides with known antibacterial activity in vitro and/or in vivo was tested in Drosophila Although most peptides and peptoids that were effective in vitro failed to rescue lethal effects of S. aureus infections in vivo, we found that two lantibiotics, nisin and NAI-107, rescued adult flies from fatal infections. Furthermore, NAI-107 rescued mortality of infection with the MRSA strain USA300 with an efficacy equivalent to that of vancomycin, a widely applied antibiotic for the treatment of serious MRSA infections. These results establish Drosophila as a useful model for in vivo drug evaluation of antibacterial peptides. PMID- 27381395 TI - Aspergillus fumigatus Intrinsic Fluconazole Resistance Is Due to the Naturally Occurring T301I Substitution in Cyp51Ap. AB - Aspergillus fumigatus intrinsic fluconazole resistance has been demonstrated to be linked to the CYP51A gene, although the precise molecular mechanism has not been elucidated yet. Comparisons between A. fumigatus Cyp51Ap and Candida albicans Erg11p sequences showed differences in amino acid residues already associated with fluconazole resistance in C. albicans The aim of this study was to analyze the role of the natural polymorphism I301 in Aspergillus fumigatus Cyp51Ap in the intrinsic fluconazole resistance phenotype of this pathogen. The I301 residue in A. fumigatus Cyp51Ap was replaced with a threonine (analogue to T315 at Candida albicans fluconazole-susceptible Erg11p) by changing one single nucleotide in the CYP51A gene. Also, a CYP51A knockout strain was obtained using the same parental strain. Both mutants' antifungal susceptibilities were tested. The I301T mutant exhibited a lower level of resistance to fluconazole (MIC, 20 MUg/ml) than the parental strain (MIC, 640 MUg/ml), while no changes in MIC were observed for other azole- and non-azole-based drugs. These data strongly implicate the A. fumigatus Cyp51Ap I301 residue in the intrinsic resistance to fluconazole. PMID- 27381396 TI - Population Pharmacokinetics of Isavuconazole from Phase 1 and Phase 3 (SECURE) Trials in Adults and Target Attainment in Patients with Invasive Infections Due to Aspergillus and Other Filamentous Fungi. AB - Isavuconazole, the active moiety of the water-soluble prodrug isavuconazonium sulfate, is a triazole antifungal agent used for the treatment of invasive fungal infections. The objective of this analysis was to develop a population pharmacokinetic (PPK) model to identify covariates that affect isavuconazole pharmacokinetics and to determine the probability of target attainment (PTA) for invasive aspergillosis patients. Data from nine phase 1 studies and one phase 3 clinical trial (SECURE) were pooled to develop the PPK model (NONMEM, version 7.2). Stepwise covariate modeling was performed in Perl-speaks-NONMEM, version 3.7.6. The area under the curve (AUC) at steady state was calculated for 5,000 patients by using Monte Carlo simulations. The PTA using the estimated pharmacodynamic (PD) target value (total AUC/MIC ratio) estimated from in vivo PD studies of invasive aspergillosis over a range of MIC values was calculated using simulated patient AUC values. A two-compartment model with a Weibull absorption function and a first-order elimination process adequately described plasma isavuconazole concentrations. The mean estimate for isavuconazole clearance was 2.360 liters/h (percent coefficient of variation [%CV], 34%), and the mean AUC from 0 to 24 h (AUC0-24) was ~100 mg.h/liter. Clearance was approximately 36% lower in Asians than in Caucasians. The PTA calculated over a range of MIC values by use of the nonneutropenic murine efficacy index corresponding to 90% survival indicated that adequate isavuconazole exposures were achieved in >90% of simulated patients to treat infections with MICs up to and including 1 mg/liter according to European Committee on Antimicrobial Susceptibility Testing methodology and in >90% of simulated patients for infections with MICs up to and including 0.5 mg/liter according to Clinical and Laboratory Standards Institute methodology. The highest MIC result for PTA was the same for Caucasian and Asian patients. PMID- 27381398 TI - Structural and Mutagenic Analysis of Metallo-beta-Lactamase IMP-18. AB - IMP-type metallo-beta-lactamases (MBLs) are exogenous zinc metalloenzymes that hydrolyze a broad range of beta-lactams, including carbapenems. Here we report the crystal structure of IMP-18, an MBL cloned from Pseudomonas aeruginosa, at 2.0-A resolution. The overall structure of IMP-18 resembles that of IMP-1, with an alphabeta/betaalpha "folded sandwich" configuration, but the loop that covers the active site has a distinct conformation. The relationship between IMP-18's loop conformation and its kinetic properties was investigated by replacing the amino acid residues that can affect the loop conformation (Lys44, Thr50, and Ile69) in IMP-18 with those occupying the corresponding positions in the well described enzyme IMP-1. The replacement of Thr50 with Pro considerably modified IMP-18's kinetic properties, specifically those pertaining to meropenem, with the kcat/Km value increased by an order of magnitude. The results indicate that this is a key residue that defines the kinetic properties of IMP-type beta-lactamases. PMID- 27381397 TI - Interspecies Dissemination of a Mobilizable Plasmid Harboring blaIMP-19 and the Possibility of Horizontal Gene Transfer in a Single Patient. AB - Carbapenemase-producing Gram-negative bacilli have been a global concern over the past 2 decades because these organisms can cause severe infections with high mortality rates. Carbapenemase genes are often carried by mobile genetic elements, and resistance plasmids can be transferred through conjugation. We conducted whole-genome sequencing (WGS) to demonstrate that the same plasmid harboring a metallo-beta-lactamase gene was detected in two different species isolated from a single patient. Metallo-beta-lactamase-producing Achromobacter xylosoxidans (KUN4507), non-metallo-beta-lactamase-producing Klebsiella pneumoniae (KUN4843), and metallo-beta-lactamase-producing K. pneumoniae (KUN5033) were sequentially isolated from a single patient and then analyzed in this study. Antimicrobial susceptibility testing, molecular typing (pulsed-field gel electrophoresis and multilocus sequence typing), and conjugation analyses were performed by conventional methods. Phylogenetic and molecular clock analysis of K. pneumoniae isolates were performed with WGS, and the nucleotide sequences of plasmids detected from these isolates were determined using WGS. Conventional molecular typing revealed that KUN4843 and KUN5033 were identical, whereas the phylogenetic tree analysis revealed a slight difference. These two isolates were separated from the most recent common ancestor 0.74 years before they were isolated. The same resistance plasmid harboring blaIMP-19 was detected in metallo beta-lactamase-producing A. xylosoxidans and K. pneumoniae Although this plasmid was not self-transferable, the conjugation of this plasmid from A. xylosoxidans to non-metallo-beta-lactamase-producing K. pneumoniae was successfully performed. The susceptibility patterns for metallo-beta-lactamase-producing K. pneumoniae and the transconjugant were similar. These findings supported the possibility of the horizontal transfer of plasmid-borne blaIMP-19 from A. xylosoxidans to K. pneumoniae in a single patient. PMID- 27381400 TI - The DNA Polymerase Gamma R953C Mutant Is Associated with Antiretroviral Therapy Induced Mitochondrial Toxicity. AB - We found a heterozygous C2857T mutation (R953C) in polymerase gamma (Pol-gamma) in an HIV-infected patient with mitochondrial toxicity. The R953C Pol-gamma mutant binding affinity for dCTP is 8-fold less than that of the wild type. The R953C mutant shows a 4-fold decrease in discrimination of analog nucleotides relative to the wild type. R953 is located on the "O-helix" that forms the substrate deoxynucleoside triphosphate (dNTP) binding site; the interactions of R953 with E1056 and Y986 may stabilize the O-helix and affect polymerase activity. PMID- 27381399 TI - Broad-Spectrum Antimicrobial Effects of Photocatalysis Using Titanium Dioxide Nanoparticles Are Strongly Potentiated by Addition of Potassium Iodide. AB - Photocatalysis describes the excitation of titanium dioxide nanoparticles (a wide band gap semiconductor) by UVA light to produce reactive oxygen species (ROS) that can destroy many organic molecules. This photocatalysis process is used for environmental remediation, while antimicrobial photocatalysis can kill many classes of microorganisms and can be used to sterilize water and surfaces and possibly to treat infections. Here we show that addition of the nontoxic inorganic salt potassium iodide to TiO2 (P25) excited by UVA potentiated the killing of Gram-positive bacteria, Gram-negative bacteria, and fungi by up to 6 logs. The microbial killing depended on the concentration of TiO2, the fluence of UVA light, and the concentration of KI (the best effect was at 100 mM). There was formation of long-lived antimicrobial species (probably hypoiodite and iodine) in the reaction mixture (detected by adding bacteria after light), but short-lived antibacterial reactive species (bacteria present during light) produced more killing. Fluorescent probes for ROS (hydroxyl radical and singlet oxygen) were quenched by iodide. Tri-iodide (which has a peak at 350 nm and a blue product with starch) was produced by TiO2-UVA-KI but was much reduced when methicillin resistant Staphylococcus aureus (MRSA) cells were also present. The model tyrosine substrate N-acetyl tyrosine ethyl ester was iodinated in a light dose dependent manner. We conclude that UVA-excited TiO2 in the presence of iodide produces reactive iodine intermediates during illumination that kill microbial cells and long-lived oxidized iodine products that kill after light has ended. PMID- 27381403 TI - Blunt Force Trauma in Veterinary Forensic Pathology. AB - Veterinary pathologists commonly encounter lesions of blunt trauma. The development of lesions is affected by the object's mass, velocity, size, shape, and angle of impact and by the plasticity and mobility of the impacted organ. Scrape, impact, and pattern abrasions cause localized epidermal loss and sometimes broken hairs and implanted foreign material. Contusions are best identified after reflecting the skin, and must be differentiated from coagulopathies and livor mortis. Lacerations-traumatic tissue tears-may have irregular margins, bridging by more resilient tissue, deviation of the wound tail, crushed hairs, and unilateral abrasion. Hanging or choking can cause circumferential cervical abrasions, contusions and rupture of hairs, hyoid bone fractures, and congestion of the head. Other special forms of blunt trauma include fractured nails, pressure sores, and dog bites. Ocular blunt trauma causes extraocular and intraocular hemorrhages, proptosis, or retinal detachment. The thoracic viscera are relatively protected from blunt trauma but may develop hemorrhages in intercostal muscles, rib fractures, pulmonary or cardiac contusions or lacerations with subsequent hemothorax, pneumothorax, or cardiac arrhythmia. The abdominal wall is resilient and moveable, yet the liver and spleen are susceptible to traumatic laceration or rupture. Whereas extravasation of blood can occur after death, evidence of vital injury includes leukocyte infiltration, erythrophagocytosis, hemosiderin, reparative lesions of fibroblast proliferation, myocyte regeneration in muscle, and callus formation in bone. Understanding these processes aids in the diagnosis of blunt force trauma including estimation of the age of resulting injuries. PMID- 27381401 TI - Antiprion Activity of DB772 and Related Monothiophene- and Furan-Based Analogs in a Persistently Infected Ovine Microglia Culture System. AB - The transmissible spongiform encephalopathies are fatal neurodegenerative disorders characterized by the misfolding of the native cellular prion protein (PrP(C)) into the accumulating, disease-associated isoform (PrP(Sc)). Despite extensive research into the inhibition of prion accumulation, no effective treatment exists. Previously, we demonstrated the inhibitory activity of DB772, a monocationic phenyl-furan-benzimidazole, against PrP(Sc) accumulation in sheep microglial cells. In an effort to determine the effect of structural substitutions on the antiprion activity of DB772, we employed an in vitro strategy to survey a library of structurally related, monothiophene- and furan based compounds for improved inhibitory activity. Eighty-nine compounds were screened at 1 MUM for effects on cell viability and prion accumulation in a persistently infected ovine microglia culture system. Eleven compounds with activity equivalent to or higher than that of DB772 were identified as preliminary hit compounds. For the preliminary hits, cytotoxicities and antiprion activities were compared to calculate the tissue culture selectivity index. A structure-activity relationship (SAR) analysis was performed to determine molecular components contributing to antiprion activity. To investigate potential mechanisms of inhibition, effects on PrP(C) and PrP(Sc) were examined. While inhibition of total PrP(C) was not observed, the results suggest that a potential target for inhibition at biologically relevant concentrations is through PrP(C) misfolding to PrP(Sc) Further, SAR analysis suggests that two structural elements were associated with micromolar antiprion activity. Taken together, the described data provide a foundation for deeper investigation into untested DB compounds and in the design of effective therapeutics. PMID- 27381404 TI - Ethico-legal issues related to ovarian tissue transplantation. AB - Ovarian tissue transplantation (OTT) is a promising experimental method which may soon become well-established. In cases of minor oncology, where patients' fertility is seriously threatened by treatment, it may be applied as a unique fertility preservation option. OTT has a dual nature ('organ' and 'gamete'). Many stakeholders are involved, including donor, recipient, child, health-care providers and society at large. There is considerable uncertainty about the long term consequences of the application of OTT and OT cryopreservation (OTC). Thus, application of OTT gives rise to a number of very different ethico-legal issues and dilemmas which are hard to solve coherently through a principlism-based bioethical approach. This study focuses on such dilemmas and attempts to review them. The role of virtue ethics, which may be combined with principlism, is essential to solve such dilemmas coherently and reasonably. Dealing with conflicts of ethical principles equivalent between them, or moral dilemmas without available answers and mind-sharing in a difficult interpersonal process of decision making, requires a virtue-based ethical approach. Besides, ethico legal issues related to OTC/OTT are complex issues requiring a multidisciplinary approach (ethical considerations, medical, psychological and social evaluations etc.). We stress the crucial role of multidisciplinary Ethics Committee which is considered indispensable for each reproductive health-care unit practicing OTC/OTT. PMID- 27381402 TI - A Novel Endonuclease Inhibitor Exhibits Broad-Spectrum Anti-Influenza Virus Activity In Vitro. AB - Antiviral drugs are important in preventing and controlling influenza, particularly when vaccines are ineffective or unavailable. A single class of antiviral drugs, the neuraminidase inhibitors (NAIs), is recommended for treating influenza. The limited therapeutic options and the potential risk of antiviral resistance are driving the search for additional small-molecule inhibitors that act on influenza virus proteins. The acid polymerase (PA) of influenza viruses is a promising target for new antivirals because of its essential role in initiating virus transcription. Here, we characterized a novel compound, RO-7, identified as a putative PA endonuclease inhibitor. RO-7 was effective when added before the cessation of genome replication, reduced polymerase activity in cell-free systems, and decreased relative amounts of viral mRNA and genomic RNA during influenza virus infection. RO-7 specifically inhibited the ability of the PA endonuclease domain to cleave a nucleic acid substrate. RO-7 also inhibited influenza A viruses (seasonal and 2009 pandemic H1N1 and seasonal H3N2) and B viruses (Yamagata and Victoria lineages), zoonotic viruses (H5N1, H7N9, and H9N2), and NAI-resistant variants in plaque reduction, yield reduction, and cell viability assays in Madin-Darby canine kidney (MDCK) cells with nanomolar to submicromolar 50% effective concentrations (EC50s), low toxicity, and favorable selective indices. RO-7 also inhibited influenza virus replication in primary normal human bronchial epithelial cells. Overall, RO-7 exhibits broad-spectrum activity against influenza A and B viruses in multiple in vitro assays, supporting its further characterization and development as a potential antiviral agent for treating influenza. PMID- 27381405 TI - Nocardioides intraradicalis sp. nov., isolated from the roots of Psammosilene tunicoides W. C. Wu et C. Y. Wu. AB - A Gram-stain-positive, non-spore-forming and non-motile strain, designated YIM DR1091T, was isolated from the roots of Psammosilene tunicoides W. C. Wu et C. Y. Wu collected from Gejiu, Yunnan, China. The taxonomic position of strain YIM DR1091T was investigated by a polyphasic approach. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain YIM DR1091T is a member of the genus Nocardioides. Strain YIM DR1091T was closely related to Nocardioides pyridinolyticus OS4T, Nocardioides caricicola YC6903T, Nocardioides hankookensis DS-30T and Nocardioides aquiterrae GW-9T, with which it shared pairwise 16S rRNA gene sequence similarities of 97.6, 97.5, 97.2 and 97.2 %, respectively. Mean DNA DNA relatedness values between strain YIM DR1091T and related type strains N. pyridinolyticus JCM 10369T, N. caricicola JCM 17686T, N. hankookensis JCM 15302T and N. aquiterrae JCM 11813T were 44.9+/-1.7, 50.2+/-1.3, 46.8+/-0.9 and 43.0+/ 0.2 %, respectively. The respiratory menaquinone for strain YIM DR1091T was MK 8(H4) while the major fatty acids (>5 %) were iso-C16 : 0, C17 : 1omega8c, C17 : 0, iso-C15 : 0 and iso-C14 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol and three unidentified phospholipids. Whole-cell hydrolysates contained mannose, ribose, glucose and galactose, along with ll diaminopimelic acid as the diagnostic diamino acid in the peptidoglycan. The DNA G+C content was 74.6 mol%. Phenotypic, phylogenetic and chemotaxonomic data indicated that strain YIM DR1091T represents a novel species of the genus Nocardioides, for which the name Nocardioides intraradicalis sp. nov. is proposed. The type strain is YIM DR1091T (=JCM 30632T=CGMCC4.7251T). PMID- 27381406 TI - The preservative effect of Thai propolis extract on the viability of human periodontal ligament cells. AB - BACKGROUND/AIM: Tooth avulsion causes an injury to the periodontal ligament (PDL). The success of tooth replantation depends on the quantity and quality of PDL cells. The aim of this study was to examine the preservative and proliferative effects of Thai propolis extract, previously shown to exert anti inflammatory and antioxidant activities, on human PDL cells. MATERIALS AND METHODS: Ninety-six premolars were left to air dry for 30 min and stored in Hank's balanced salt solution (HBSS), milk, or various concentrations of propolis extract from 0.25 to 10 mg ml-1 for 3 h. PDL cells were isolated by collagenase and trypsin digestion, and their viability was determined by a trypan blue dye exclusion assay. PDL tissues were also scraped off the root surface and cultured to determine cell growth and morphology. The alamarBlue(r) and BrdU assays were performed to determine the cytotoxic and proliferative effects of the extract on cultured PDL cells, respectively. RESULTS: A non-toxic dose of 2.5 mg ml-1 of propolis extract yielded the greatest percentage of cell viability (78.84 +/- 3.34%), which was significantly higher than those of the other concentrations (P < 0.001). Nevertheless, this percentage was not significantly different from that of HBSS (80.14 +/- 2.44%; P = 1.00), but was significantly higher than that of milk (71.27 +/- 2.79%; P < 0.001). The cells grown from PDL explants looked like fibroblasts. However, 2.5 mg ml-1 of the extract did not induce PDL cell proliferation. CONCLUSION: Thai propolis extract at 2.5 mg ml-1 appears to be the most effective dose for preserving the viability of PDL cells, and this was comparable to HBSS. PMID- 27381407 TI - Globus pallidus internus deep brain stimulation for the treatment of status dystonicus in tardive dystonia. PMID- 27381408 TI - Metal-Free [2+2+2] Cycloaddition of Ynamides and Nitriles: Mild and Regioselective Synthesis of Fully Substituted Pyridines. AB - A metal-free trimolecular [2+2+2] cycloaddition of internal ynamides and nitriles for de novo synthesis of fully substituted pyridines is disclosed. With the versatile Bronsted acid catalyst HNTf2 , the mild intermolecular cyclotrimerization process proceeds with complementary chemoselectivity and excellent regioselectivity. PMID- 27381409 TI - Passing through - reasons why migrant doctors in Ireland plan to stay, return home or migrate onwards to new destination countries. AB - BACKGROUND: International recruitment is a common strategy used by high-income countries to meet their medical workforce needs. Ireland, despite training sufficient doctors to meet its internal demand, continues to be heavily dependent on foreign-trained doctors, many of whom may migrate onwards to new destination countries. A cross-sectional study was conducted to measure and analyse the factors associated with the migratory intentions of foreign doctors in Ireland. METHODS: A total of 366 non-European nationals registered as medical doctors in Ireland completed an online survey assessing their reasons for migrating to Ireland, their experiences whilst working and living in Ireland, and their future plans. Factors associated with future plans - whether to remain in Ireland, return home or migrate to a new destination country - were tested by bivariate and multivariate analyses, including discriminant analysis. RESULTS: Of the 345 foreign doctors who responded to the question regarding their future plans, 16 % of whom were Irish-trained, 30 % planned to remain in Ireland, 23 % planned to return home and 47 % to migrate onwards. Country of origin, personal and professional reasons for migrating, experiences of training and supervision, opportunities for career progression, type of employment contract, citizenship status, and satisfaction with life in Ireland were all factors statistically significantly associated with the three migratory outcomes. CONCLUSION: Reported plans may not result in enacted emigration. However, the findings support a growing body of evidence highlighting dissatisfaction with current career opportunities, contributing to the emigration of Irish doctors and onward migration of foreign doctors. Implementation of the WHO Global Code, which requires member states to train and retain their own health workforce, could also help reduce onward migration of foreign doctors to new destination countries. Ireland has initiated the provision of tailored postgraduate training to doctors from Pakistan, enabling these doctors to return home with improved skills of benefit to the source country. PMID- 27381410 TI - Personality Characteristics, Job Stressors, and Job Satisfaction: Main and Interaction Effects on Psychological and Physical Health Conditions of Italian Schoolteachers. AB - The study proposed an application of the transactional model of stress in teaching elaborated by Travers and Cooper in 1996, and aimed to investigate the influence of personality characteristics (coping strategies, type A behaviors), situational characteristics (sources of pressure), and perceived job satisfaction in the prediction of teachers' psychophysical health conditions. The Italian version of the Teacher Stress Questionnaire was administered to 621 teachers. Logistic regression was used to evaluate significant main and interaction effects of personality characteristics, situational characteristics, and perceived job satisfaction on teachers' self-reported psychophysical health conditions. The findings highlighted specific coping strategies (focused on the problem, on innovation, and on hobbies and pastimes) and dimensions of job satisfaction (related to intrinsic aspects of job and to employee relations) buffering the negative effects of several job stressors. Type A behaviors and coping strategies focused on mobilized social support, suppression of stress, and not confronting the situation had main and interactions with negative effects on psychophysical health. Findings confirmed the necessity to run multi-factor research to analyze the different combinations of individual and situational variables implicated in negative health outcomes and to highlight the most significant buffering or increasing associations. PMID- 27381411 TI - Examining Competing Models of Transformational Leadership, Leadership Trust, Change Commitment, and Job Satisfaction. AB - This study discusses the influence of transformational leadership on job satisfaction through assessing six alternative models related to the mediators of leadership trust and change commitment utilizing a data sample (N = 341; M age = 32.5 year, SD = 5.2) for service promotion personnel in Taiwan. The bootstrap sampling technique was used to select the better fitting model. The tool of hierarchical nested model analysis was applied, along with the approaches of bootstrapping mediation, PRODCLIN2, and structural equation modeling comparison. The results overall demonstrate that leadership is important and that leadership role identification (trust) and workgroup cohesiveness (commitment) form an ordered serial relationship. PMID- 27381412 TI - Role of Student Well-Being: A Study Using Structural Equation Modeling. AB - The present study explored the effects of academic and social self-efficacy beliefs on students' well-being at school, academic engagement, and achievement outcome. Well-being at school is conceptualized as a central mediator of students' engagement and learning in achievement contexts. It was hypothesized that well-being at school would mediate the effects of social and academic self efficacy beliefs on engagement and achievement outcome. This research focus has credence and may provide grounding for educational-social interventions. A cohort of 284 (122 girls, 162 boys) Year 11 secondary school students participated in this correlational study. A theoretical-conceptual model was explored and tested using structural equation modeling. Subsequent structural equation modeling analyses provided moderate support for the hypothesized model. The results showed that both academic and social self-efficacy depended on each other in their effect on well-being at school. Both academic engagement and well-being at school served as partial mediators of the effects of academic and social self-efficacy on academic engagement. PMID- 27381413 TI - Door-in-the-Face and But-You-Are-Free: Testing the Effect of Combining Two No Pressure Compliance Paradigms. AB - According to Howard's proposal of chaining compliance techniques and based on the proximity of interpretation of their effects, this study aimed to test a combination of two paradigms: a door-in-the-face request that makes a high-cost request before the target request and the but-you-are-free request that adds an evocation of freedom to the request. Two experiments were conducted (N = 120 and 1,292) to promote donations to non-profit organizations. There were four conditions. Participants were approached according to the door-in-the-face procedure, to the but-you-are-free procedure, to a combination of both of them, or directly in a control condition. There was an increase of compliance rates in experimental conditions compared to the control condition and an increase in the average amount donated in the combination condition compared to the control condition in the second study. Results are discussed in terms of responsibility and guilt mechanisms, and future developments are proposed. PMID- 27381414 TI - Investigation of the Structural Relationships Between Social Support, Self Compassion, and Subjective Well-Being in Korean Elite Student Athletes. AB - The study examined whether self-compassion mediates the relationship between social support and subjective well-being, as perceived by athletes. It also investigated the structural relationships between these variables. Participants were 333 athletes attending high school or university. Structural equation analysis showed that self-compassion partially mediated the relationship between social support and subjective well-being. To test the stability of the model, a multiple group analysis was performed according to sex of participant and school level, and this demonstrated that the model had similar fit to the data regardless of group. The confirmation that self-compassion plays an intermediary role in the relationship between social support and subjective well-being demonstrates that self-compassionate attitudes can be fostered by social support, and that, in turn, has a positive effect on an individual's subjective well being. PMID- 27381415 TI - Antibiotics for acute respiratory tract infections in primary care. PMID- 27381416 TI - Screening and identification of a specific peptide for targeting hypoxic hepatoma cells. AB - The biological behaviors of residual hepatoma cells after transarterial embolization therapy, which exist in a hypoxic or even anaerobic tumor microenvironment, differ from the tumor cells under normoxic conditions. This study aimed to use a phage display peptide library for in vivo and in vitro screening to obtain a peptide which could specifically bind to hypoxic hepatoma cells, allowing further targeted diagnosis and treatment for liver cancer. In this study, hypoxic hepatoma cells HepG2 (targeted cells), and normal liver cells HL-7702 (control cells), were utilized to perform three rounds of in vitro screening using a phage-displayed 7-mer peptide library. In addition, hypoxic HepG2 were subcutaneously injected into nude mice to establish a hepatocarcinoma model, followed by performing three rounds of in vivo screening on the phages identified from the in vitro screening. The products from the screening were further identified using ELISA and immunofluorescence staining on cells and tissues. The results indicated that the P11 positive clone had the highest binding effect with hypoxic hepatoma cells. The sequence of the exogenous insert fragment of P11 positive clone was obtained by sequencing: GSTSFSK. The binding assay indicated that GSTSFSK could specifically bind to hypoxic hepatoma cells and hepatocarcinoma tissues. This 7-mer peptide has the potential to be developed as an useful molecular to the targeting diagnosis and treatment of residual hepatoma cells after transarterial chemoembolization. PMID- 27381417 TI - Adverse maternal exposures, methylation of glucocorticoid-related genes and perinatal outcomes: a systematic review. AB - AIM: Maternal environmental exposures affect perinatal outcomes through epigenetic placental changes. We examine the literature addressing associations between adverse maternal exposures, perinatal outcomes and methylation of key genes regulating placental cortisol metabolism. METHODS: We searched three databases for studies that examined NR3C1 and HSD11beta1/HSD11 beta 2 methylation with maternal exposures or perinatal outcomes. Nineteen studies remained after screening. We followed Cochrane's PRISMA reporting guidelines (2009). RESULTS: NR3C1 and HSD11 beta methylation were associated with adverse infant neurobehavior, stress response, blood pressure and physical development. In utero exposure to maternal stress, nutrition, preeclampsia, smoking and diabetes were associated with altered NR3C1 and HSD11 beta methylation. CONCLUSION: NR3C1 and HSD11 beta methylation are useful biomarkers of specific environmental stressors associated with important perinatal outcomes that determine pediatric and adult disease risk. PMID- 27381419 TI - The clinical utilization of radiation therapy in Korea between 2009 and 2013. AB - PURPOSE: The purpose of this study was to estimate the clinical utilization of radiation therapy (RT) in Korea between 2009 and 2013. MATERIALS AND METHODS: We analyzed open claims data from the Health Insurance Review and Assessment Service. The subjects were patients who had diagnostic codes C00-C97 or D00-D48 according to the 10th revision of the International Classification of Diseases, with procedure codes indicating RT treatment. RESULTS: The total number of patients who received RT in 2009, 2010, 2011, 2012, and 2013 were 45,571, 49,593, 54,671, 59,172, and 61,485, respectively. Among them, the total numbers of male and female patients were 20,780/24,791 in 2009, 22,711/26,882 in 2010, 24,872/29,799 in 2011, 27,101/32,071 in 2012, and 27,941/33,544 in 2013. The five cancers that were most frequently treated with RT between 2009 and 2012 were breast, lung, colorectal, liver, and uterine cervical cancers. However, the fifth most common cancer treated with RT that replaced uterine cervical cancer in 2013 was prostate cancer. The three leading types of cancer among the male patients were lung, colorectal, and liver cancers, whereas in female patients, they were breast, uterine cervical, and lung cancers. The type of cancer most commonly treated by RT was cancer of the central nervous system in patients aged 20 years or less, breast cancer in patients aged 30-50 years, and lung cancer in patients aged 60 years or more. CONCLUSION: Data from this study provided the clinical utilization of RT in Korea between 2009 and 2013. PMID- 27381420 TI - Surface-functionalized hydrophilic monolayer of titanate and its application for dopamine detection. AB - A surface-functionalized hydrophilic charge-neutral monolayer of titanate was exfoliated from the precursor layered composite in aqueous media without addition of a delamination agent. The hydrophilic monolayer was applied for the detection of dopamine based on visible-light absorption originating from charge-transfer excitation from adsorbed dopamine to titanate. PMID- 27381418 TI - The Arabidopsis Golgi-localized GDP-L-fucose transporter is required for plant development. AB - Nucleotide sugar transport across Golgi membranes is essential for the luminal biosynthesis of glycan structures. Here we identify GDP-fucose transporter 1 (GFT1), an Arabidopsis nucleotide sugar transporter that translocates GDP-L fucose into the Golgi lumen. Using proteo-liposome-based transport assays, we show that GFT preferentially transports GDP-L-fucose over other nucleotide sugars in vitro, while GFT1-silenced plants are almost devoid of L-fucose in cell wall derived xyloglucan and rhamnogalacturonan II. Furthermore, these lines display reduced L-fucose content in N-glycan structures accompanied by severe developmental growth defects. We conclude that GFT1 is the major nucleotide sugar transporter for import of GDP-L-fucose into the Golgi and is required for proper plant growth and development. PMID- 27381422 TI - Protective effects of cilostazol against hemorrhagic stroke: Current and future perspectives. AB - Cilostazol is a phosphodiesterase-3 inhibitor and is known to have pleiotropic effects including antiplatelet and vasodilatation effects and protective effects on endothelial cells. Cilostazol also reportedly reduced stroke recurrence, poststroke intracranial hemorrhage, and extracranial bleeding in a meta-analysis. Although it is known that cilostazol has the potential to suppress hemorrhagic stroke, the precise mechanisms remained unclear. Therefore, we evaluated the protective effects and mechanisms of cilostazol against hemorrhagic stroke. We found that cilostazol prevented the hemorrhagic transformation induced by focal cerebral ischemia in mice treated with intravenous tissue plasminogen activator or warfarin via protecting endothelial cells and tight junction proteins. We also demonstrated that cilostazol attenuated collagenase-induced intracranial hemorrhage in mice. In vitro studies showed that endothelial cells, pericytes, tight junction proteins, adherence junction proteins, and the basement membrane, which are all components of the blood-brain barrier, were protected by the administration of cilostazol following collagenase injury. These results suggested that cilostazol reduces hemorrhagic stroke by protecting the entire blood-brain barrier. Here, we review the protective effects of cilostazol on the blood-brain barrier that result in the prevention of hemorrhagic stroke, discuss the results we obtained using multiple hemorrhagic stroke models, and introduce potential future applications of cilostazol. PMID- 27381421 TI - High Level of Anaphylatoxin C5a Predicts Poor Clinical Outcome in Patients with Clear Cell Renal Cell Carcinoma. AB - Anaphylatoxin C5a, a potent pro-inflammatory peptide produced in the process of complement activation, was proved to have a vital role in tumor initiation and progession by previous investigations. However whether it could act as a prognostic marker remains unknown. Here we retrospectively enrolled 272 ccRCC patients undergoing nephrectomy in Zhongshan Hospital, Shanghai between 2005 and 2007. C5a level was assessed by immunohistochemistry and its association with clinicopathologic features and prognosis were evaluated. Our results indicated that high tumoral C5a level was associated with poor overall survival (OS) (hazard ratio = 1.753, 95% CI 1.068-2.878, P = 0.026). In addition, tumoral C5a could significantly stratify patients' prognosis both in advanced stage (TNM III + IV) and intermediate/high risk group (SSIGN score >=4) (P < 0.001 and = 0.008, respectively). Furthermore, incorporating tumoral C5a with other parameters could improve the predicting accuracy, compared with TNM and SSIGN system (c-index = 0.789, 0.713 and 0.727, respectively). In conclusion, tumoral C5a is an independent adverse prognostic biomarker for clinical outcome of ccRCC patients after nephectomy. PMID- 27381423 TI - An interactive ICT platform for early assessment and management of patient reported concerns among older adults living in ordinary housing - development and feasibility. AB - AIMS AND OBJECTIVES: To develop and test feasibility and acceptability of an interactive ICT platform integrated in a tablet for collecting and managing patient-reported concerns of older adults in home care. BACKGROUND: Using different ICT applications, for example interactive tablets for self-assessment of health and health issues based on health monitoring as well as other somatic and psychiatric monitoring systems may improve quality of life, staff and patient communication and feelings of being reassured. The European Commission hypothesises that introduction of ICT applications to the older population will enable improved health. However, evidence-based and user-based applications are scarce. DESIGN: The design is underpinned by the Medical Research Council's complex intervention evaluation framework. A mixed-method approach was used combining interviews with older adults and healthcare professionals, and logged quantitative data. METHODS: In cooperation with a health management company, a platform operated by an interactive application for reporting and managing health related problems in real time was developed. Eight older adults receiving home care were recruited to test feasibility. They were equipped with the application and reported three times weekly over four weeks, and afterwards interviewed about their experiences. Three nurses caring for them were interviewed. The logged data were extracted as a coded file. RESULTS: The older adults reported as instructed, in total 107 reports (Mean 13). The most frequent concerns were pain, fatigue and dizziness. The older adults experienced the application as meaningful with overall positive effects as well as potential benefits for the nurses involved. CONCLUSIONS: The overall findings in this study indicated high feasibility among older adults using the ICT platform. The study's results support further development of the platform, as well as tests in full-scale studies and in other populations. RELEVANCE TO CLINICAL PRACTICE: An ICT platform increased the older adults' perception of involvement and facilitated communication between the patient and nurses. PMID- 27381424 TI - Corticosterone dysregulation exacerbates disease progression in the R6/2 transgenic mouse model of Huntington's disease. AB - Huntington's disease (HD) is a genetic neurological disorder that causes severe and progressive motor, cognitive, psychiatric, and metabolic symptoms. There is a robust, significant elevation in circulating levels of the stress hormone, cortisol, in HD patients; however, the causes and consequences of this elevation are largely uncharacterized. Here, we evaluated whether elevated levels of corticosterone, the rodent homolog of cortisol, contributed to the development of symptomology in transgenic HD mice. Wild-type (WT) and transgenic R6/2 mice were given either 1) adrenalectomy with WT-level corticosterone replacement (10ng/ml), 2) adrenalectomy with high HD-level corticosterone replacement (60ng/ml), or 3) sham surgery without replacement. R6/2 mice on HD-level replacement showed severe and rapid weight loss (p<0.05) and a shorter latency to death (p<0.01) relative to the HD mice on WT-level replacement. We further evaluated basal and stress induced levels of circulating corticosterone in R6/2 mice throughout the course of their life. We found that R6/2 transgenic HD mice display a spontaneous elevation in circulating corticosterone levels that became significant at 10weeks of age. Furthermore, we identified significant dysregulation of circadian rhythmicity of corticosterone release measured over a 24h period compared to wild type controls. Unexpectedly, we found that R6/2 transgenic mice show a blunted corticosterone response to restraint stress, compared to wild-type mice. Together, these data provide further evidence that HPA-axis activity is abnormal in R6/2 mice, and highlight the important role that cortisol plays in HD symptom development. Our findings suggest that cortisol-reducing therapeutics may be of value in improving HD patient quality of life. PMID- 27381425 TI - Neuromodulation of the neural circuits controlling the lower urinary tract. AB - The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner. PMID- 27381426 TI - Immigration, tourism and the heart: a descriptive analysis of cardiovascular diseases in different populations. PMID- 27381428 TI - Five different types of eta(8)-cyclooctatetraenyl-lanthanide half-sandwich complexes from one ligand set, including a "giant neodymium wheel". AB - The lithium-cyclopropylethynylamidinates Li[c-C3H5-C[triple bond, length as m dash]C-C(NR)2] (1a: R = (i)Pr, 1b: R = cyclohexyl (Cy)) have been used as precursors for the preparation of five new series of half-sandwich complexes. These complexes contain the large flat cyclooctatetraenyl ligand (C8H8(2-), commonly abbreviated as COT), and were isolated as solvated, unsolvated and inverse sandwich complexes. Treatment of the halide precursors [(COT)Pr(MU Cl)(THF)2]2 with 1b and [(COT)Nd(MU-Cl)(THF)2]2 with 1a and 1b in THF in a 1 : 2 molar ratio, respectively, afforded (COT)Ln[MU-c-C3H5-C[triple bond, length as m dash]C-C(NR)2]2Li(L) (2: Ln = Pr, R = Cy, L = Et2O; 3: Ln = Nd, R = (i)Pr, L = THF; 4: Ln = Nd, R = Cy, L = THF). Treatment of the dimeric cerium(iii) bis(cyclopropylethynylamidinate) complexes [{c-C3H5-C[triple bond, length as m dash]C-C(NR)2}2Ce(MU-Cl)(THF)]2 (5: R = (i)Pr; 6: R = Cy) in situ with K2C8H8 in a 1 : 1 molar ratio in THF at room temperature afforded the inverse-sandwich complexes (MU-eta(8):eta(8)-COT)[Ce{c-C3H5-C[triple bond, length as m-dash]C C(NR)2}2]2 (7: R = (i)Pr; 8: R = Cy). This reaction represents a new method for encapsulation of a planar (C8H8)(2-) ring in lanthanide complexes containing amidinate ligands in the outer decks. Novel unsolvated dinuclear lanthanide half sandwich complexes were prepared by using the precursors 1a, 1b and COT(2-). Unlike the complexes 2-4, the reaction of [(COT)Pr(MU-Cl)(THF)2]2 with 1a afforded the unsolvated centrosymmetric complex [(COT)Pr(MU-c-C3H5-C[triple bond, length as m-dash]C-C(N(i)Pr)2)]2 (9). These dimeric structures could be also accessed by reaction of LnCl3 (Ln = Ce or Nd) with 1a or 1b and K2COT in a 1 : 1 : 1 molar ratio as a one-pot reaction to give novel [(COT)Ln(MU-c-C3H5-C[triple bond, length as m-dash]C-C(NR)2)]2 complexes (10: Ln = Ce, R = (i)Pr; 11: Ln = Ce, R = Cy; 12: Ln = Nd, R = (i)Pr). Similar treatment of HoCl3 with 1a or 1b and K2COT as three-component reactions in a 1 : 1 : 1 molar ratio afforded the solvated half-sandwich complexes (COT)Ho(c-C3H5-C[triple bond, length as m-dash]C C(NR)2)(THF) (13: R = (i)Pr; 14: R = Cy). A unique multidecker sandwich complex [(MU-eta(8):eta(8)-COT){Nd(c-C3H5-C[triple bond, length as m-dash]C-C(NCy)2)(MU Cl)}2]4 (15) was prepared by reaction of anhydrous NdCl3 with K2COT and 1b in a one-pot reaction. The solid state structure of 15 revealed the presence of an unprecedented macrocyclic sandwich compound ("giant neodymium wheel") consisting of four COT rings sandwiched between eight Nd(3+) ions, and each Nd(3+) ion is bonded to one amidinate ligand and bridged by two chlorine atoms with the neighbouring Nd(3+) ion. PMID- 27381427 TI - [Perceived barriers to active commuting to school: reliability and validity of a scale]. AB - OBJECTIVE: To examine the reliability and validity of a scale to measure perceived barriers to active commuting to school among Spanish young people. METHOD: The validity of the scale was assessed in a sample of 465 adolescents (14 18 years) using a confirmatory factor analysis and studying its association with self-reported active commuting to school. The reliability of the instrument was evaluated in a sub-sample that completed the scale twice separated by a one-week interval. RESULTS: The results showed that the barriers scale had satisfactory fit indices, and two factors were determined. The first included environment- and safety-related items (alpha=0.72), while the other concerned planning and psychosocial items (alpha=0.64). Active commuting to school showed significant correlations with the total score of the barriers scale (rho=-0.27; p <0.001), with the environmental/safety barriers (rho=-0.22; p <0.001), as well as with the planning/psychosocial barriers (rho=-0.29; p <0.001). Test-retest ICCs for the barriers ranged from 0.68 to 0.77. CONCLUSION: The developed scale has acceptable validity and good reliability to assess barriers to active commuting to school among Spanish young people. PMID- 27381429 TI - Teletoxicology: Patient Assessment Using Wearable Audiovisual Streaming Technology. AB - BACKGROUND: Audiovisual streaming technologies allow detailed remote patient assessment and have been suggested to change management and enhance triage. The advent of wearable, head-mounted devices (HMDs) permits advanced teletoxicology at a relatively low cost. A previously published pilot study supports the feasibility of using the HMD Google Glass(r) (Google Inc.; Mountain View, CA) for teletoxicology consultation. This study examines the reliability, accuracy, and precision of the poisoned patient assessment when performed remotely via Google Glass(r). METHODS: A prospective observational cohort study was performed on 50 patients admitted to a tertiary care center inpatient toxicology service. Toxicology fellows wore Google Glass(r) and transmitted secure, real-time video and audio of the initial physical examination to a remote investigator not involved in the subject's care. High-resolution still photos of electrocardiograms (ECGs) were transmitted to the remote investigator. On-site and remote investigators recorded physical examination findings and ECG interpretation. Both investigators completed a brief survey about the acceptability and reliability of the streaming technology for each encounter. Kappa scores and simple agreement were calculated for each examination finding and electrocardiogram parameter. Reliability scores and reliability difference were calculated and compared for each encounter. RESULTS: Data were available for analysis of 17 categories of examination and ECG findings. Simple agreement between on-site and remote investigators ranged from 68 to 100 % (median = 94 %, IQR = 10.5). Kappa scores could be calculated for 11/17 parameters and demonstrated slight to fair agreement for two parameters and moderate to almost perfect agreement for nine parameters (median = 0.653; substantial agreement). The lowest Kappa scores were for pupil size and response to light. On a 100-mm visual analog scale (VAS), mean comfort level was 93 and mean reliability rating was 89 for on-site investigators. For remote users, the mean comfort and reliability ratings were 99 and 86, respectively. The average difference in reliability scores between on-site and remote investigators was 2.6, with the difference increasing as reliability scores decreased. CONCLUSION: Remote evaluation of poisoned patients via Google Glass(r) is possible with a high degree of agreement on examination findings and ECG interpretation. Evaluation of pupil size and response to light is limited, likely by the quality of streaming video. Users of Google Glass(r) for teletoxicology reported high levels of comfort with the technology and found it reliable, though as reported reliability decreased, remote users were most affected. Further study should compare patient centered outcomes when using HMDs for consultation to those resulting from telephone consultation. PMID- 27381430 TI - Numerical indices based on circulating tumor DNA for the evaluation of therapeutic response and disease progression in lung cancer patients. AB - Monitoring of disease/therapeutic conditions is an important application of circulating tumor DNA (ctDNA). We devised numerical indices, based on ctDNA dynamics, for therapeutic response and disease progression. 52 lung cancer patients subjected to the EGFR-TKI treatment were prospectively collected, and ctDNA levels represented by the activating and T790M mutations were measured using deep sequencing. Typically, ctDNA levels decreased sharply upon initiation of EGFR-TKI, however this did not occur in progressive disease (PD) cases. All 3 PD cases at initiation of EGFR-TKI were separated from other 27 cases in a two dimensional space generated by the ratio of the ctDNA levels before and after therapy initiation (mutation allele ratio in therapy, MART) and the average ctDNA level. For responses to various agents after disease progression, PD/stable disease cases were separated from partial response cases using MART (accuracy, 94.7%; 95% CI, 73.5-100). For disease progression, the initiation of ctDNA elevation (initial positive point) was compared with the onset of objective disease progression. In 11 out of 28 eligible patients, both occurred within +/ 100 day range, suggesting a detection of the same change in disease condition. Our numerical indices have potential applicability in clinical practice, pending confirmation with designed prospective studies. PMID- 27381431 TI - Evolutionary pressures on microbial metabolic strategies in the chemostat. AB - Protein expression is shaped by evolutionary processes that tune microbial fitness. The limited biosynthetic capacity of a cell constrains protein expression and forces the cell to carefully manage its protein economy. In a chemostat, the physiology of the cell feeds back on the growth conditions, hindering intuitive understanding of how changes in protein concentration affect fitness. Here, we aim to provide a theoretical framework that addresses the selective pressures and optimal evolutionary-strategies in the chemostat. We show that the optimal enzyme levels are the result of a trade-off between the cost of their production and the benefit of their catalytic function. We also show that deviations from optimal enzyme levels are directly related to selection coefficients. The maximal fitness strategy for an organism in the chemostat is to express a well-defined metabolic subsystem known as an elementary flux mode. Using a coarse-grained, kinetic model of Saccharomyces cerevisiae's metabolism and growth, we illustrate that the dynamics and outcome of evolution in a chemostat can be very counter-intuitive: Strictly-respiring and strictly fermenting strains can evolve from a common ancestor. This work provides a theoretical framework that relates a kinetic, mechanistic view on metabolism with cellular physiology and evolutionary dynamics in the chemostat. PMID- 27381432 TI - Toxicokinetics and time-variable toxicity of cadmium in Oppia nitens Koch (Acari: Oribatida). AB - The soil-living mite Oppia nitens Koch has recently been proposed as a promising test species for the ecotoxicological risk assessment of contaminated boreal soils. Adding oribatid mites to the assemblage of test species for soil is highly desirable given the enormous diversity and ecological significance of these microarthropods. The authors aimed at revealing how toxicity, lethal body concentration, and bioaccumulation of cadmium (Cd) changed over a period of 7 wk when mites were exposed to Cd-spiked natural soils. The estimated median lethal concentration (LC50) values showed a gradual decrease with time, but a steady state was not reached within 7 wk. Estimates for lethal body concentration varied from 44 MUg Cd/g to 91 MUg Cd/g dry body weight, with a tendency to increase with time. The estimated 50% effective concentration (EC50) for effects on reproduction after 7-wk exposure was 345 MUg Cd/g dry soil. Accumulation of Cd in mites was extremely variable but overall showed a nonsaturating increase. A simple 1-compartment toxicokinetic model did not describe the data well. The analysis suggests that O. nitens has a storage-detoxification strategy that is not at equilibrium under chronic exposure. Considering the tiny body size of the animal, it is remarkable that long exposure times are necessary to reveal chronic toxicity. The use of oribatids provides a clear added value to soil risk assessment but trades off with exposure length. Environ Toxicol Chem 2017;36:408 413. (c) 2016 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. PMID- 27381434 TI - [20th Meeting of the Editors Group of the Journals of the Cono Sur Paediatric Societies]. PMID- 27381433 TI - [Vitamin D deficiency in children admitted to the paediatric intensive care unit]. AB - INTRODUCTION: Vitamin D is essential for bone health, as well as for cardiovascular and immune function. In critically ill adults vitamin D deficiency (VDD) is common, and is associated with sepsis and higher critical illness severity. OBJECTIVES: To establish the prevalence of VDD and its association with clinically relevant outcomes in children admitted to a Paediatric Intensive Care Unit (PICU) in Concepcion, Chile. PATIENTS AND METHOD: Prospective observational cohort study in 90 consecutive children admitted to the PICU in a university general hospital. Blood was collected on admission to PICU and analysed for 25-OH D levels. Severity of illness and vasopressor use were assessed using PRISM, PELOD, and vasoactive-inotropic score (VIS) score. VDD was defined as a serum 25 OH-D level<20ng/ml. Relative risks (RR) were calculated to determine the association between VDD and relevant clinical outcomes. RESULTS: Mean (SD) serum vitamin D (25-OH-D) level in the cohort was 22.8 (1.0)ng/ml. The prevalence of VDD was 43.3%. VDD was associated with vasopressors use (RR1.6; 95%CI: 1.2-2.3; P<.01), mechanical ventilation (RR2.2; 95%CI: 1.2-3.9, P<.01), septic shock (RR1.9; 95%CI: 1.3-2.9, P<.001), and fluid bolus>40ml/kg in the first 24h of admission (RR 1.5; 95%CI: 1.1-2.1, P<.05). CONCLUSIONS: In this study, VDD at PICU admission was prevalent in critically ill children and was associated with adverse clinical outcomes. Further studies are needed to assess the potential benefit of optimizing vitamin D status in the PICU. PMID- 27381436 TI - Photoreactions with a Twist: Atropisomerism-Driven Divergent Reactivity of Enones with UV and Visible Light. AB - Light-induced transformation of atropisomeric and achiral enones displays divergent reactivity. Photocyclization leading to 3,4-dihydroquinolin-2-one was observed with achiral enone carboxamide, whereas the atropisomeric enone carboxamides underwent hydrogen abstraction leading to spiro-beta-lactams. Detailed photochemical, photophysical, and theoretical investigations have provided insight into this divergent reactivity and selectivity. PMID- 27381435 TI - [Internal consistency and criterion validity and reliability of the Mexican Version of the Child Behavior Checklist 1.5-5 (CBCL/1.5-5)]. AB - OBJECTIVE: To investigate the validity and internal consistency of the Mexican version of the CBCL/1.5 -5 that assesses the most common psychopathology in pre school children in clinical and epidemiological settings. PATIENTS AND METHOD: A total of 438 parents from two groups, clinical-psychiatric (N= 62) and community (N= 376) completed the CBCL/1.5-5/Mexican version. RESULTS: The internal consistency was high for total problems alpha=0.95, and internalized alpha=0.89 and externalized alpha=0.91 subscales. The test re-test (one week) using the intraclass correlation coefficient (ICC) was >= 0.95 for the internalized, externalized, and total problems subscales. The ROC curve for the criterion status of clinically-referred vs. non-referred using the total problems scale >= 24 resulted in an AUC (area under curve) of 0.77, a specificity 0.73, and a sensitivity of 0.70. CONCLUSIONS: The CBCL/1.5 -5/Mexican version is a reliable and valid tool. PMID- 27381438 TI - Biochemical and Pathophysiological Premises to Positron Emission Tomography With Choline Radiotracers. AB - Choline is a quaternary ammonium base that represents an essential component of phospholipids and cell membranes. Malignant transformation is associated with an abnormal choline metabolism at a higher levels with respect to those exclusively due to cell multiplication. The use of Positron Emission Tomography/Computed Tomography (PET/CT) with radiocholine (RCH), labeled with 11 C or 18 F, is widely diffuse in oncology, with main reference to restaging of patients with prostate cancer. The enhanced concentration in neoplasm is based not only on the increasing growing rate, but also on more specific issues, such as the augmented uptake in malignant cells due to the up-regulation of choline kinase. Furthermore the role of hypoxia in decreasing choline's uptake determine an in vivo concentration only in well oxygenated tumors, with a lower uptake when malignancy increases, that is, in tumors positive at 18 F-Fluoro-deoxyglucose. In this paper we have analyzed the most important issues related to the possible utilization of RCH in diagnostic imaging of human cancer. J. Cell. Physiol. 232: 270-275, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27381437 TI - Cyclic di-GMP contributes to adaption and virulence of Bacillus thuringiensis through a riboswitch-regulated collagen adhesion protein. AB - Cyclic di-GMP is a ubiquitous second messenger that regulates diverse cellular processes in bacteria by binding to various protein or riboswitch effectors. In Bacillus thuringiensis BMB171, a c-di-GMP riboswitch termed Bc2 RNA resides in the 5'-untranslated region (5'-UTR) of an mRNA that encodes a collagen adhesion protein (Cap). The expression of cap was strongly repressed in parent strain BMB171 because of the presence of Bc2 RNA but was significantly promoted in the Bc2 RNA markerless deletion mutant. Bc2 RNA acts as a genetic "on" switch, which forms an anti-terminator structure to promote cap read-through transcription upon c-di-GMP binding. As a result, cap transcription was de-repressed under high c-di GMP levels. Therefore, Bc2 RNA regulates cap expression using a repression/de repression model. Bc2 RNA-regulated Cap was also found to be tightly associated with motility, aggregation, exopolysaccharide secretion, biofilm formation, and virulence of B. thuringiensis BMB171 against its host insect Helicoverpa armigera. PMID- 27381439 TI - Retraction: Impact of high-fat feeding on basic helix-loop-helix transcription factors controlling enteroendocrine cell differentiation. PMID- 27381440 TI - Suppression of Jasmonic Acid-Mediated Defense by Viral-Inducible MicroRNA319 Facilitates Virus Infection in Rice. AB - MicroRNAs (miRNAs) are pivotal modulators of plant development and host-virus interactions. However, the roles and action modes of specific miRNAs involved in viral infection and host susceptibility remain largely unclear. In this study, we show that Rice ragged stunt virus (RRSV) infection caused increased accumulation of miR319 but decreased expression of miR319-regulated TCP (TEOSINTE BRANCHED/CYCLOIDEA/PCF) genes, especially TCP21, in rice plants. Transgenic rice plants overexpressing miR319 or downregulating TCP21 exhibited disease-like phenotypes and showed significantly higher susceptibility to RRSV in comparison with the wild-type plants. In contrast, only mild disease symptoms were observed in RRSV-infected lines overexpressing TCP21 and especially in the transgenic plants overexpressing miR319-resistant TCP21. Both RRSV infection and overexpression of miR319 caused the decreased endogenous jasmonic acid (JA) levels along with downregulated expression of JA biosynthesis and signaling related genes in rice. However, treatment of rice plants with methyl jasmonate alleviated disease symptoms caused by RRSV and reduced virus accumulation. Taken together, our results suggest that the induction of miR319 by RRSV infection in rice suppresses JA-mediated defense to facilitate virus infection and symptom development. PMID- 27381441 TI - A Layered Defense Strategy Mediated by Rice E3 Ubiquitin Ligases against Diverse Pathogens. PMID- 27381442 TI - Quantification of Membrane Protein Dynamics and Interactions in Plant Cells by Fluorescence Correlation Spectroscopy. AB - Deciphering the dynamics of protein and lipid molecules on appropriate spatial and temporal scales may shed light on protein function and membrane organization. However, traditional bulk approaches cannot unambiguously quantify the extremely diverse mobility and interactions of proteins in living cells. Fluorescence correlation spectroscopy (FCS) is a powerful technique to describe events that occur at the single-molecule level and on the nanosecond to second timescales; therefore, FCS can provide data on the heterogeneous organization of membrane systems. FCS can also be combined with other microscopy techniques, such as super resolution techniques. More importantly, FCS is minimally invasive, which makes it an ideal approach to detect the heterogeneous distribution and dynamics of key proteins during development. In this review, we give a brief introduction about the development of FCS and summarize the significant contributions of FCS in understanding the organization of plant cell membranes and the dynamics and interactions of membrane proteins. We also discuss the potential applications of this technique in plant biology. PMID- 27381443 TI - Distant eQTLs and Non-coding Sequences Play Critical Roles in Regulating Gene Expression and Quantitative Trait Variation in Maize. AB - A detailed understanding of genetic architecture of mRNA expression by millions of genetic variants is important for studying quantitative trait variation. In this study, we identified 1.25M SNPs with a minor allele frequency greater than 0.05 by combining reduced genome sequencing (GBS), high-density array technologies (600K), and previous deep RNA-sequencing data from 368 diverse inbred lines of maize. The balanced allelic frequencies and distributions in a relatively large and diverse natural panel helped to identify expression quantitative trait loci (eQTLs) associated with more than 18 000 genes (63.4% of tested genes). We found that distant eQTLs were more frequent (~75% of all eQTLs) across the whole genome. Thirteen novel associated loci affecting maize kernel oil concentration were identified using the new dataset, among which one intergenic locus affected the kernel oil variation by controlling expression of three other known oil-related genes. Altogether, this study provides resources for expanding our understanding of cellular regulatory mechanisms of transcriptome variation and the landscape of functional variants within the maize genome, thereby enhancing the understanding of quantitative variations. PMID- 27381444 TI - A proteomic and genetic analysis of the Neurospora crassa conidia cell wall proteins identifies two glycosyl hydrolases involved in cell wall remodeling. AB - A proteomic analysis of the conidial cell wall identified 35 cell wall proteins. A comparison with the proteome of the vegetative hyphae showed that 16 cell wall proteins were shared, and that these shared cell wall proteins were cell wall biosynthetic proteins or cell wall structural proteins. Deletion mutants for 34 of the genes were analyzed for phenotypes indicative of conidial cell wall defects. Mutants for two cell wall glycosyl hydrolases, the CGL-1 beta-1,3 glucanase (NCU07523) and the NAG-1 exochitinase (NCU10852), were found to have a conidial separation phenotype. These two enzymes function in remodeling the cell wall between adjacent conidia to facilitate conidia formation and dissemination. Using promoter::RFP and promoter::GFP constructs, we demonstrated that the promoters for 15 of the conidia-specific cell wall genes, including cgl-1 and nag 1, provided for conidia-specific gene expression or for a significant increase in their expression during conidiation. PMID- 27381445 TI - A novel nanostructured supramolecular hydrogel self-assembled from tetraphenylethylene-capped dipeptides. AB - Herein, we report a tetraphenylethylene-diglycine (TPE-GG) hydrogelator from a systematic study of TPE-capped dipeptides with various amphiphilic properties. From a chemical design, we found that the hydrogelation of TPE-GG molecules can be utilized to generate supramolecular nanostructures with a large TPE-based nanobelt width (~300 nm) and lateral dimension ratio (>30 fold). In addition, TPE GG has the lowest molecular weight and minimum number of atoms compared to any TPE-capped peptide hydrogelator reported to date. This minimal self-assembled hydrogelator can fundamentally achieve the gel features compared with other TPE capped peptides. A combined experimental and computational study indicates the pi pi interactions, electrostatic interactions and hydrogen-bonding interactions are the major driving forces behind the formation of self-assembled nanobelts. This study demonstrates the importance of structure-property relationships and provides new insights into the design of supramolecular nanomaterials. PMID- 27381446 TI - The value of ultrasonographic tubo-ovarian abscess morphology in predicting whether patients will require surgical treatment. AB - OBJECTIVE: To determine if the ultrasonographic morphology of a tubo-ovarian abscess (TOA) could be used to predict if a patient will require surgical treatment. METHOD: A retrospective cohort study reviewed medical records from patients diagnosed with TOA via ultrasonography between January 2009 and January 2014 at a tertiary referral center in Turkey. Patients with pelvic inflammatory disease and an inflammatory adnexal mass, identified during sonographic examination, were included in the study. Ultrasonographic morphology, demographic characteristics, and clinical and laboratory findings were compared between patients who required surgical treatment and those who did not. RESULTS: Records were included from 164 patients; medical therapy was successful in 121 (73.8%) patients and 43 (26.2%) required surgical treatment. TOA morphology was identified, using ultrasonography, as unilocular cystic, complex multicystic mass, or pyosalpinx in 56 (34.1%), 73 (44.5%), and 35 (21.3%) patients, respectively. No correlation was present between ultrasonographic TOA morphology and patients requiring surgical treatment (all P>0.05). Multivariate analyses demonstrated that an abscess larger than 6.5 cm in size (P=0.027), fever at admission (P<0.001), and parity greater than two (P=0.026) were independent predictors of patients requiring surgical treatment for TOA. CONCLUSION: Although increased TOA size, fever at admission, and parity were associated with increased odds of patients with TOA requiring surgical treatment, ultrasonographic TOA morphology was not. PMID- 27381447 TI - Upregulation of MicroRNA-214 Contributes to the Development of Vascular Remodeling in Hypoxia-induced Pulmonary Hypertension Via Targeting CCNL2. AB - Hypoxia-induced pulmonary hypertension (PH), which is characterized by vascular remodeling of blood vessels, is a significant complication of chronic obstructive pulmonary disease (COPD). In this study, we screened 13 candidate miRNAs in pulmonary artery smooth muscle cells (PASMCs) harvested from COPD patients with PH (n = 18) and normal controls (n = 15) and found that the expression of miR-214 was differentially expressed between these two groups. Additionally, cyclin L2 (CCNL2) was validated as a target of miR-214 in PASMCs using a luciferase assay. Based on real-time PCR, immunohistochemistry and western blot, the expression of CCNL2 was substantially downregulated in PASMCs from COPD patients with PH compared with those from normal controls. Moreover, the relationship between miRNA and mRNA expression was confirmed using real-time PCR and western blot in PASMCs transfected with miR-214 mimics. Furthermore, the introduction of miR-214 significantly promoted the proliferation of PASMCs by suppressing cell apoptosis, and this effect was mediated by the downregulation of CCNL2. Exposure of PASMCs to hypoxia significantly increased the expression of miR-214, decreased the expression of CCNL2, and promoted cell proliferation. However, these effects were significantly attenuated by the introduction of miR-214 inhibitors, which significantly downregulated miR-214 expression and upregulated CCNL2 expression. PMID- 27381448 TI - Systematic review of the health and societal effects of medication organisation devices. AB - BACKGROUND: Suboptimal medication adherence is a significant threat to public health and resources. Devices that organise weekly doses by time and day are commonly used to reduce unintentional non-adherence. However, there is limited evidence to support their use. This systematic review was conducted to evaluate current evidence for their efficacy, safety and costs. METHODS: A pre-defined search of electronic databases from inception to January 2013 augmented with hand searching was conducted. No limits were placed on publication date. Studies that compared organisation devices used by patients administering their own medication with standard medication packaging regardless of study design were eligible for inclusion. Studies that solely explored dispensing aspects of organisation devices were included whether or not they compared this to standard care. Screening of articles for inclusion and data extraction were completed independently by two reviewers with disagreements resolved by discussion. Outcomes were categorised into impact on health, medication adherence, healthcare utilisation, dispensing errors, supply procedures and costs. Risk of bias was also assessed. RESULTS: Seventeen studies met the inclusion criteria. Health outcomes were investigated in seven studies of which three reported a positive effect associated with organisation devices. Medication adherence was reported in eight studies of which three reported a positive effect. Three studies reported health care utilisation data but overall results are inconclusive. No optimal dispensing or supply procedures were identified. Economic assessment of the impact of organisation devices is lacking. All studies were subject to a high risk of bias. CONCLUSIONS: Evidence regarding the effects of medication organisation devices was limited, and the available evidence was susceptible to a high risk of bias. Organisation devices may help unintentional medication non adherence and could improve health outcomes. There is a strong need for more studies that explore the impact of such devices on patients, and an equally pressing need for studies that explore the impacts on healthcare services. TRIAL REGISTRATION: This systematic review is registered with PROSPERO (Registration number CRD42011001718 ). PMID- 27381449 TI - Generation and characterization of tamoxifen-inducible Pax9-CreER knock-in mice using CrispR/Cas9. AB - Pax9 encodes a paired-box homeodomain (Pax) transcription factor and is critical for the development of multiple organs. Using CrispR/Cas9-mediated homologous directed repair (HDR), we generated a new Pax9-CreER knock-in mouse line in which the CreER(T2) fusion protein is produced after synthesis of endogenous Pax9 protein. We found that tdTomato reporter expression in Pax9-CreER;tdTomato reporter mice is detectable in a similar pattern to the endogenous Pax9 expression, faithfully recapitulating the Pax9 expression domains throughout the embryo and in the adult mouse. At early embryonic stages, the tdTomato reporter is expressed first in the pharyngeal pouch region and later in the craniofacial mesenchyme, somites, limbs, and lingual papillae in the adult tongue. These results demonstrate that this new Pax9-CreER knock-in mouse line can be used for lineage tracing and genetic targeting of Pax9-expressing cells and their progeny in a temporally and spatially controlled manner during development and organogenesis. PMID- 27381450 TI - Neandertal cannibalism and Neandertal bones used as tools in Northern Europe. AB - Almost 150 years after the first identification of Neandertal skeletal material, the cognitive and symbolic abilities of these populations remain a subject of intense debate. We present 99 new Neandertal remains from the Troisieme caverne of Goyet (Belgium) dated to 40,500-45,500 calBP. The remains were identified through a multidisciplinary study that combines morphometrics, taphonomy, stable isotopes, radiocarbon dating and genetic analyses. The Goyet Neandertal bones show distinctive anthropogenic modifications, which provides clear evidence for butchery activities as well as four bones having been used for retouching stone tools. In addition to being the first site to have yielded multiple Neandertal bones used as retouchers, Goyet not only provides the first unambiguous evidence of Neandertal cannibalism in Northern Europe, but also highlights considerable diversity in mortuary behaviour among the region's late Neandertal population in the period immediately preceding their disappearance. PMID- 27381451 TI - Expression of astrocyte elevated gene-1 protein in ameloblastomas, keratocystic odontogenic tumors, and dentigerous cysts. AB - BACKGROUND: Benign epithelial odontogenic tumors such as ameloblastoma and keratocystic odontogenic tumor (KCOT) may exhibit an aggressive clinical course reminiscent of malignancies. Recent studies have indicated that astrocyte elevated gene-1 (AEG-1) is highly expressed in a variety of malignant neoplasms and its overexpression is associated with tumor invasion, metastasis, and poor survival. However, the role of AEG-1 in odontogenic tumors and cysts is still undiscovered. METHODS: Immunohistochemical staining of AEG-1 was performed in 42 cases of ameloblastoma, 29 cases of KCOT, and 19 cases of dentigerous cyst. Correlations between AEG-1 expression and clinical parameters of ameloblastomas or KCOTs were statistically analyzed. RESULTS: AEG-1-positive staining was found in 37 (88%) of 42 ameloblastomas and in 24 (83%) of 29 KCOTs. None of 19 dentigerous cysts were positive for AEG-1 protein. For ameloblastomas, AEG-1 protein expression was significantly higher in ameloblast-like cells than in stellate reticulum-like cells (P = 0.003). For KCOTs, AEG-1 protein was diffusely expressed in all lining epithelial cells except the superficial parakeratinized cells. Moreover, the frequency of cortical plate perforation was significantly higher in ameloblastomas with high AEG-1 expression than in ameloblastomas with low or negative AEG-1 expression (P = 0.043). CONCLUSION: Significantly higher expression of AEG-1 protein in ameloblastomas and KCOTs than in dentigerous cysts and significantly greater frequency of cortical plate perforation in high AEG-1 expressed ameloblastomas than in low or negative AEG-1-expressed ameloblastomas may imply the high potential of AEG-1 to serve as a locally invasive biomarker and a target for novel therapy. PMID- 27381452 TI - Protective effect of two essential oils isolated from Rosa damascena Mill. and Lavandula angustifolia Mill, and two classic antioxidants against L-dopa oxidative toxicity induced in healthy mice. AB - Levodopa (L-dopa) is a "gold standard" and most effective symptomatic agent in the Parkinson's disease (PD) treatment. The several treatments have been developed in an attempt to improve PD treatment, but most patients were still levodopa dependent. The issue of toxicity was raised in vitro studies, and suggests that L-dopa can be toxic to dopaminergic neurons, but it is not yet entirely proven. L-dopa prolonged treatment is associated with motor complications and some limitations. Combining the L-dopa therapy with antioxidants can reduce related sideeffects and provide symptomatic relief. The natural antioxidants can be isolated from any plant parts such as seeds, leaves, roots, bark, etc., and their extracts riched in phenols can retard the oxidative degradation of the lipids, proteins and DNA. Thus, study suggests that combination of essential oils (Rose oil and Lavender oil), Vitamin C and Trolox with Ldopa can reduce oxidative toxicity, and may play a key role in ROS/RNS disarm. PMID- 27381453 TI - Anti-inflammatory and protective effects of saffron extract in ischaemia/reperfusion-induced acute kidney injury. AB - AIM: Inflammation is one of the major challenges in the management of ischaemia/reperfusion (I/R)-induced acute kidney injury. Our aim was to assess the anti-inflammatory and protective effects of saffron extract against I/R induced renal disturbances. METHODS: A total of 35 male Wistar rats were randomly divided into five groups (n = 7) as sham, I/R and three groups of I/R that were pretreated with different doses of saffron extract (5 mg/kg, 10 mg/kg, or 20 mg/kg) intraperitoneally. The I/R-induced renal inflammation was assessed by measuring leukocyte infiltration and mRNA expression levels of intercellular adhesion molecule-1 and tumour necrotic factor-alpha. For the assessment of oxidative stress, thiobarbituric acid reactive species and antioxidant capacity of kidneys were measured in the right kidneys. In addition, plasma creatinine and urea-nitrogen concentrations were determined for renal functional disturbances. Statistical analysis was performed using one-way analysis of variance using the Duncan post hoc test. RESULTS: The I/R increased all of the measured parameters, except for the tissue level of ferric reducing/antioxidant power, which decreased. Pretreatment with saffron extract in all doses significantly reduced the severity of these disturbances in such a way that there were no significant differences between the FRAP level and urea-nitrogen concentrations between the sham and all three saffron extract-treated groups. However, the saffron extract could decrease the plasma creatinine concentration, malondialdehyde level, tumour necrotic factor-alpha and intercellular adhesion molecule-1 expression and leukocyte infiltration in a dose-dependent manner. CONCLUSION: The present study showed anti-inflammatory, anti-oxidative and protective effects for the hydro ethanolic extract of saffron in I/R-induced acute kidney injury. PMID- 27381454 TI - Erratum to: Urban Health Research in Africa: Themes and Priority Research Questions. PMID- 27381455 TI - Statins and Reduced Risk of Liver Cancer: Evidence for Confounding. AB - A negative association of statin use with liver cancer risk has been reported frequently. We added laboratory measurements, to our knowledge not included in previous investigations, to a case-control analysis of 2877 case patients and 142 850 matched control subjects enrolled in Kaiser Permanente Northern California. Addressing confounding by indication by restricting subjects to those with elevated cholesterol greatly attenuated the negative association; eg, the multivariable-adjusted odds ratio (OR) rose from 0.41 (95% confidence interval [CI] = 0.35 to 0.49) to 0.87 (95% CI = 0.55 to 1.39) for receipt of 18 or more prescriptions. Confounding by contraindication was addressed by controlling for degree of abnormality of liver function tests, alanine or aspartate transaminase, measured within one year of the elevated cholesterol and strongly related to risk. The negative association of statins disappeared for all numbers of prescriptions received, with an odds ratio of 1.21 (95% CI = 0.53 to 2.75) for 18 or more prescriptions. Findings cast doubt on the causality of the frequently observed preventive association. PMID- 27381456 TI - Recipe for High Moment Materials with Rare-earth and 3d Transition Metal Composites. AB - Materials with high volume magnetization are perpetually needed for the generation of sufficiently large magnetic fields by writer pole of magnetic hard disks, especially for achieving increased areal density in storage media. In search of suitable materials combinations for this purpose, we have employed density functional theory to predict the magnetic coupling between iron and gadolinium layers separated by one to several monolayers of 3d transition metals (Sc-Zn). We demonstrate that it is possible to find ferromagnetic coupling for many of them and in particular for the early transition metals giving rise to high moment. Cr and Mn are the only elements able to produce a significant ferromagnetic coupling for thicker spacer layers. We also present experimental results on two trilayer systems Fe/Sc/Gd and Fe/Mn/Gd. From the experiments, we confirm a ferromagnetic coupling between Fe and Gd across a 3 monolayers Sc spacer or a Mn spacer thicker than 1 monolayer. In addition, we observe a peculiar dependence of Fe/Gd magnetic coupling on the Mn spacer thickness. PMID- 27381457 TI - Role of Exchange Protein Directly Activated by Cyclic AMP Isoform 1 in Energy Homeostasis: Regulation of Leptin Expression and Secretion in White Adipose Tissue. AB - Epacs (exchange proteins directly activated by cyclic AMP [cAMP]) act as downstream effectors of cAMP and play important roles in energy balance and glucose homeostasis. While global deletion of Epac1 in mice leads to heightened leptin sensitivity in the hypothalamus and partial protection against high-fat diet (HFD)-induced obesity, the physiological functions of Epac1 in white adipose tissue (WAT) has not been explored. Here, we report that adipose tissue-specific Epac1 knockout (AEKO) mice are more prone to HFD-induced obesity, with increased food intake, reduced energy expenditure, and impaired glucose tolerance. Despite the fact that AEKO mice on HFD display increased body weight, these mice have decreased circulating leptin levels compared to their wild-type littermates. In vivo and in vitro analyses further reveal that suppression of Epac1 in WAT decreases leptin mRNA expression and secretion by inhibiting cAMP response element binding (CREB) protein and AKT phosphorylation, respectively. Taken together, our results demonstrate that Epac1 plays an important role in regulating energy balance and glucose homeostasis by promoting leptin expression and secretion in WAT. PMID- 27381458 TI - Transcriptional Modulator Ifrd1 Regulates Osteoclast Differentiation through Enhancing the NF-kappaB/NFATc1 Pathway. AB - Bone homeostasis is maintained by the synergistic actions of bone-resorbing osteoclasts and bone-forming osteoblasts. Here, we show that the transcriptional coactivator/repressor interferon-related developmental regulator 1 (Ifrd1) is expressed in osteoclast lineages and represents a component of the machinery that regulates bone homeostasis. Ifrd1 expression was transcriptionally regulated in preosteoclasts by receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL) through activator protein 1. Global deletion of murine Ifrd1 increased bone formation and decreased bone resorption, leading to a higher bone mass. Deletion of Ifrd1 in osteoclast precursors prevented RANKL-induced bone loss, although no bone loss was observed under normal physiological conditions. RANKL dependent osteoclastogenesis was impaired in vitro in Ifrd1-deleted bone marrow macrophages (BMMs). Ifrd1 deficiency increased the acetylation of p65 at residues K122 and K123 via the inhibition of histone deacetylase-dependent deacetylation in BMMs. This repressed the NF-kappaB-dependent transcription of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), an essential regulator of osteoclastogenesis. These findings suggest that an Ifrd1/NF-kappaB/NFATc1 axis plays a pivotal role in bone remodeling in vivo and represents a therapeutic target for bone diseases. PMID- 27381459 TI - Function of Conserved Topological Regions within the Saccharomyces cerevisiae Basal Transcription Factor TFIIH. AB - TFIIH is a 10-subunit RNA polymerase II basal transcription factor with a dual role in DNA repair. TFIIH contains three enzymatic functions and over 30 conserved subdomains and topological regions. We systematically tested the function of these regions in three TFIIH core module subunits, i.e., Ssl1, Tfb4, and Tfb2, in the DNA translocase subunit Ssl2, and in the kinase module subunit Tfb3. Our results are consistent with previously predicted roles for the Tfb2 Hub, Ssl2 Lock, and Tfb3 Latch regions, with mutations in these elements typically having severe defects in TFIIH subunit association. We also found unexpected roles for other domains whose function had not previously been defined. First, the Ssl1-Tfb4 Ring domains are important for TFIIH assembly. Second, the Tfb2 Hub and HEAT domains have an unexpected role in association with Tfb3. Third, the Tfb3 Ring domain is important for association with many other TFIIH subunits. Fourth, a partial deletion of the Ssl1 N-terminal extension (NTE) domain inhibits TFIIH function without affecting subunit association. Finally, we used site-specific cross-linking to localize the Tfb3-binding surface on the Rad3 Arch domain. Our cross-linking results suggest that Tfb3 and Rad3 have an unusual interface, with Tfb3 binding on two opposite faces of the Arch. PMID- 27381460 TI - The park-view effect: Residential development is higher at the boundaries of protected areas. AB - Land-use changes in the surrounding of protected areas might compromise their conservation efficacy, and thus the potential attractive effect that protected areas may exert on urban development is particularly concerning. We investigated whether the proximity to protected areas in a region (Lombardy, Italy) with a high density of urban areas and parks may increase the likelihood of residential development. The main change around protected areas was the loss of open areas (mostly due to development processes at the expense of arable land), which was higher in proximity of parks. Changes in residential discontinuous development were significantly and negatively related to proximity to parks, whereas changes in productive developments were unrelated to park proximity. The higher likelihood of residential development in proximity to parks is likely due to the attraction exerted by parks. The severe loss of open areas and increase of residential development around parks heavily impacted on habitat availability for a declining bird species (Alauda arvensis). Conservation policies considering also what happens around protected areas are urgently needed. PMID- 27381461 TI - Reaction cross sections and thermal rate constant for Cl(-) + CH3Br -> ClCH3 + Br(-) from J-dependent quantum scattering calculations. AB - Employing dimensionality-reduced time-independent quantum scattering theory and summation over all possible total angular momentum states, initial-state selected reaction cross sections for the exothermic gas-phase bimolecular nucleophilic substitution (SN2) reaction Cl(-) + CH3Br -> ClCH3 + Br(-) have been calculated. The carbon-halogen bonds and the rotation of the methyl halides are taken into account. In agreement with previous calculations for J = 0, initial rotational motion of CH3Br decreases the reaction probability and consequently the cross sections. The experimentally obtained thermal rate constant for 300 K is reproduced within the experimental error. For lower temperatures, it is calculated to be below the experimental values but shows the same strong increase for T -> 0. PMID- 27381462 TI - Inflammatory Bowel Disease Drugs: A Focus on Autophagy. AB - Inflammatory bowel disease [IBD] is characterized by chronic inflammation of the gastrointestinal tract. Medications such as corticosteroids, thiopurines, immunomodulators and biologic agents are used to induce and maintain remission; however, response to these drugs is variable and can diminish over time. Defective autophagy has been strongly linked to IBD pathogenesis, with evidence showing that enhancing autophagy may be therapeutically beneficial by regulating inflammation and clearing intestinal pathogens. It is plausible that the therapeutic effects of some IBD drugs are mediated in part through modulation of the autophagy pathway, with studies investigating a wide range of diseases and cell types demonstrating autophagy pathway regulation by these agents. This review will highlight the current evidence, both in vitro and in vivo, for the modulation of autophagy by drugs routinely used in IBD. A clearer understanding of their mechanisms of action will be invaluable to utilize these drugs in a more targeted and personalized manner in this diverse and often complex group of patients. PMID- 27381464 TI - Naegleria fowleri after 50 years: is it a neglected pathogen? AB - It has been 50 years since the first case of primary amoebic meningoencephalitis (PAM), an acute and rapidly fatal disease of the central nervous system (CNS), was reported in Australia. It is now known that the aetiological agent of PAM is Naegleria fowleri, an amoeba that is commonly known as 'the brain-eating amoeba'. N. fowleri infects humans of different ages who are in contact with water contaminated with this micro-organism. N. fowleri is distributed worldwide and is found growing in bodies of freshwater in tropical and subtropical environments. The number of PAM cases has recently increased, and the rate of recovery from PAM has been estimated at only 5 %. Amphotericin B has been used to treat patients with PAM. However, it is important to note that there is no specific treatment for PAM. Moreover, this amoeba is considered a neglected micro-organism. Researchers have exerted great effort to design effective drugs to treat PAM and to understand the pathogenesis of PAM over the past 50 years, such as its pathology, molecular and cellular biology, diagnosis and prevention, and its biological implications, including its pathogenic genotypes, its distribution and its ecology. Given the rapid progression of PAM and its high mortality rate, it is important that investigations continue and that researchers collaborate to gain better understanding of the pathogenesis of this disease and, consequently, to improve the diagnosis and treatment of this devastating infection of the CNS. PMID- 27381463 TI - Use of Designer G Protein-Coupled Receptors to Dissect Metabolic Pathways. AB - G protein-coupled receptors (GPCRs) regulate virtually all metabolic processes, including glucose and energy homeostasis. Recently, the use of designer GPCRs referred to as designer receptors exclusively activated by designer drug (DREADDs) has made it possible to dissect metabolically relevant GPCR signaling pathways in a temporally and spatially controlled fashion in vivo. PMID- 27381466 TI - That's not how the learning works - the paradox of Reverse Innovation: a qualitative study. AB - BACKGROUND: There are significant differences in the meaning and use of the term 'Reverse Innovation' between industry circles, where the term originated, and health policy circles where the term has gained traction. It is often conflated with other popularized terms such as Frugal Innovation, Co-development and Trickle-up Innovation. Compared to its use in the industrial sector, this conceptualization of Reverse Innovation describes a more complex, fragmented process, and one with no particular institution in charge. It follows that the way in which the term 'Reverse Innovation', specifically, is understood and used in the healthcare space is worthy of examination. METHODS: Between September and December 2014, we conducted eleven in-depth face-to-face or telephone interviews with key informants from innovation, health and social policy circles, experts in international comparative policy research and leaders in the Reverse Innovation space in the United States. Interviews were open-ended with guiding probes into the barriers and enablers to Reverse Innovation in the US context, specifically also informants' experience and understanding of the term Reverse Innovation. Interviews were recorded, transcribed and analyzed thematically using the process of constant comparison. RESULTS: We describe three main themes derived from the interviews. First, 'Reverse Innovation,' the term, has marketing currency to convince policy-makers that may be wary of learning from or adopting innovations from unexpected sources, in this case Low-Income Countries. Second, the term can have the opposite effect - by connoting frugality, or innovation arising from necessity as opposed to good leadership, the proposed innovation may be associated with poor quality, undermining potential translation into other contexts. Finally, the term 'Reverse Innovation' is a paradox - it breaks down preconceptions of the directionality of knowledge and learning, whilst simultaneously reinforcing it. CONCLUSIONS: We conclude that this term means different things to different people and should be used strategically, and with some caution, depending on the audience. PMID- 27381467 TI - Prenatal presentation of hereditary hemorrhagic telangiectasia - a report of two sibs. PMID- 27381465 TI - The genome and transcriptome of Trichormus sp. NMC-1: insights into adaptation to extreme environments on the Qinghai-Tibet Plateau. AB - The Qinghai-Tibet Plateau (QTP) has the highest biodiversity for an extreme environment worldwide, and provides an ideal natural laboratory to study adaptive evolution. In this study, we generated a draft genome sequence of cyanobacteria Trichormus sp. NMC-1 in the QTP and performed whole transcriptome sequencing under low temperature to investigate the genetic mechanism by which T. sp. NMC-1 adapted to the specific environment. Its genome sequence was 5.9 Mb with a G+C content of 39.2% and encompassed a total of 5362 CDS. A phylogenomic tree indicated that this strain belongs to the Trichormus and Anabaena cluster. Genome comparison between T. sp. NMC-1 and six relatives showed that functionally unknown genes occupied a much higher proportion (28.12%) of the T. sp. NMC-1 genome. In addition, functions of specific, significant positively selected, expanded orthogroups, and differentially expressed genes involved in signal transduction, cell wall/membrane biogenesis, secondary metabolite biosynthesis, and energy production and conversion were analyzed to elucidate specific adaptation traits. Further analyses showed that the CheY-like genes, extracellular polysaccharide and mycosporine-like amino acids might play major roles in adaptation to harsh environments. Our findings indicate that sophisticated genetic mechanisms are involved in cyanobacterial adaptation to the extreme environment of the QTP. PMID- 27381468 TI - Anaerosporomusa subterranea gen. nov., sp. nov., a spore-forming anaerobe belonging to the class Negativicutes isolated from saprolite. AB - A Gram-stain-negative, spore-forming, anaerobic bacterium designated strain RU4T was isolated from a saprolite core collected from Oak Ridge, Tennessee, USA. Cells were slightly curved rods and exhibited an outer membrane exterior to a thin cell wall. Strain RU4T formed heat-resistant endospores in late-log phase and stationary phase cultures. Under anaerobic conditions, strain RU4T grew by fermenting fumarate and maleate, but did not grow on glucose, glycerol, pyruvate, lactate, succinate, citrate, formate, acetate, propionate, butyrate or valerate. Strain RU4T did not reduce sulfate or ferric iron. The main cellular fatty acids were C17 : 0 cyclo, C16 : 0 and C15 : 0. The DNA G+C content was 52 mol%. Analysis of the 16S rRNA, rpoB, recA, infB, gyrB and atpD gene sequences indicated that the isolate is related to members of the family Sporomusaceae. Based on 92 % sequence similarity of the 16S rRNA gene to its closest relatives in the family Sporomusaceae and divergent physiological traits, the newly cultivated isolate was assigned to a novel species of a new genus, Anaerosporomusa subterranea gen. nov., sp. nov. The type strain of Anaerosporomusa subterranea is RU4T (=DSM 29728T=ATCC BAA-2723T). PMID- 27381469 TI - Lemierre's syndrome presenting as acute thyroid goiter. PMID- 27381470 TI - Nutrition Risk Screening in Patients Admitted to an Adult Emergency Department of a Brazilian University Hospital. AB - BACKGROUND: The prevalence of malnutrition in emergency units is high, and data on the nutrition risk of patients admitted in these units are scarce. The aims of this study are to determine the nutrition risk profile of individuals admitted in an emergency unit and to identify clinical, anthropometric, and laboratory attributes according to nutrition risk classification. MATERIALS AND METHODS: A total of 234 individuals in an emergency unit from 1 university hospital in Brazil were enrolled in this cross-sectional study. The nutrition risk profile was determined using the Nutrition Risk Screening 2002. Sociodemographic, clinical, anthropometric, and laboratory data were collected. Comparisons between individuals "at risk" and "not at risk" and logistic regression analyzes were performed. RESULTS: The prevalence of nutrition risk at admission was 48.7%. Patients at risk were older ( P = .031), were less educated ( P = .022), had a lower body mass index ( P < .001), had higher concentrations of C-reactive protein (CRP; P = .007), had a higher CRP/serum albumin ratio ( P = .004), had lower concentrations of serum albumin ( P = .002), and had severe weight loss ( P < .001). Altogether, this profile resulted in a longer hospital stay ( P = .004), more complications ( P = .005), and greater use of antibiotics ( P = .024). In regression analyses, low serum albumin (odds ratio [OR], 2.75; 95% confidence interval [CI], 1.23-6.13) and, higher serum CRP (OR, 1.13; 95% CI, 1.00-3.72), use of antibiotics (OR, 13.3; 95% CI, 1.59-111.16) were predictors of long hospital stay. CONCLUSION: The prevalence of nutrition risk in emergency patients was high and its profile associated with worse clinical, laboratory, and anthropometric outcomes. The use of other laboratory and clinical variables may also be a good strategy for predicting adverse outcomes in emergency units. PMID- 27381471 TI - Sodium-ion electrolytes based on ionic liquids: a role of cation-anion hydrogen bonding. AB - Recent success of the sodium-ion batteries fosters an academic interest for their investigation. Room-temperature ionic liquids (RTILs) constitute universal solvents providing non-volatility and non-flammability to electrolytes. In the present work, we consider four families of RTILs as prospective solvents for NaBF4 and NaNO3 with an inorganic salt concentration of 25 and 50 mol%. We propose a methodology to rate RTILs according to their solvation capability using parameters of the computed radial distribution functions. Hydrogen bonds between the cations and the anions of RTILs were found to indirectly favor sodium solvation, irrespective of the particular RTIL and its concentration. The best performance was recorded in the case of cholinium nitrate. The reported observations and correlations of ionic structures and properties offer important assistance to an emerging field of sodium-ion batteries. Graphical Abstract Sodium-ion electrolytes. PMID- 27381472 TI - The Code of Practice and its enduring relevance in Europe and Eastern and Southern Africa. AB - BACKGROUND: The relevance and effectiveness of the WHO Global Code of Practice on the International Recruitment of Personnel will be reviewed by the World Health Assembly in 2015. The origins of the Code of Practice and the global health diplomacy process before and after its adoption are analyzed herein. METHODS AND RESULTS: Case studies from the European and eastern and southern African regions describe in detail successes and failures of the policy implementation of the Code. In Europe, the Code is effective and even more relevant than before, but might require some tweaking. In Eastern and Southern Africa, the code is relevant but far from efficient in mitigating the negative effects of health workforce migration. CONCLUSIONS: Solutions to strengthen the Code include clarification of some of its definitions and articles, inclusion of a governance structure and asustainable and binding financing system to reimburse countries for health workforce losses due to migration, and featuring of health worker migration on global policy agendas across a range of institutional policy domains. PMID- 27381473 TI - Vitis vinifera L. cv Pinot noir pomace and lees as potential sources of bioactive compounds. AB - Food and agricultural industries generate substantial quantities of phenolic-rich by-products that could be valuable natural sources of antioxidants. The aim of this study was to identify and quantify the phenolic compounds and radical scavenging activities of two by-products (pomace and lees) from Vitis vinifera L. cv Pinot noir. We found a different distribution of phenolic classes (flavanols, flavonols, phenolic acids and stilbenes) and singular scavenging activity against free radicals (hydroxyl, superoxide and peroxyl radicals). The major class of phenolics in pomace was flavanols and in lees was flavonols, with catechin (117.9 +/- 2.5 MUg g(-1)) and quercetin (42.4 +/- 1.2 MUg g(-1)) being the most abundant individual compounds. We also found high potential on scavenging activity against superoxide radicals in pomace (80% of scavenging activity) and radical peroxyl (67% scavenging activity). These results show the possibility of using Pinot noir by-products as promising additives or as a source for the development of new products in different segments of the food and cosmetic industries. PMID- 27381474 TI - Retrospective review of factors associated with severe hospitalised community acquired influenza in a tertiary paediatric hospital in South Australia. AB - BACKGROUND: Influenza infection can result in severe disease with debilitating complications. Young children have the highest rate of influenza hospitalisations with various factors influencing influenza susceptibility and severity. OBJECTIVES: This study aimed to determine the disease burden and assess risk factors for severe hospitalised influenza in South Australian children under 5 years of age. METHODS: Influenza admissions to the tertiary paediatric hospital in South Australia from 2008 to 2012 were identified. Data from laboratory confirmed influenza cases were collected, including infecting influenza strain, co-infections, prematurity, pre-existing medical comorbidities and other potential risk factors. Predictors of high-level care were assessed using logistic regression. RESULTS: A total of 267 children with laboratory-confirmed influenza were hospitalised. Of these, 147 admissions (53%) occurred in children without underlying medical risk factors. Eighteen children (7%) required high level care, of which 11 (61%) had no underlying medical risk factors. No deaths were reported. The majority of children were unimmunised against influenza. Co infections were identified in 40% of children (n = 107). Influenza B was associated with a requirement for higher care (OR 3.7, CI 1.3-10.9, P = .02) as was a history of food allergies (OR 9.7, CI 1.5-61.4, P = .02) and iron deficiency anaemia (OR 4.8, CI 1.4-16.1, P = .01). CONCLUSIONS: Influenza can be a severe illness, even in children without underlying medical conditions. The identification of Influenza B strain, history of food allergies and iron deficiency anaemia as predictors of severity in hospitalised cases warrants further investigation and may have important implications for preventative strategies to reduce the burden of childhood influenza. PMID- 27381475 TI - Can Antibodies Protect Us Against Cardiovascular Disease? PMID- 27381476 TI - A Minimally-invasive Blood-derived Biomarker of Oligodendrocyte Cell-loss in Multiple Sclerosis. AB - Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS). Minimally invasive biomarkers of MS are required for disease diagnosis and treatment. Differentially methylated circulating-free DNA (cfDNA) is a useful biomarker for disease diagnosis and prognosis, and may offer to be a viable approach for understanding MS. Here, methylation-specific primers and quantitative real-time PCR were used to study methylation patterns of the myelin oligodendrocyte glycoprotein (MOG) gene, which is expressed primarily in myelin producing oligodendrocytes (ODCs). MOG-DNA was demethylated in O4(+) ODCs in mice and in DNA from human oligodendrocyte precursor cells (OPCs) when compared with other cell types. In the cuprizone-fed mouse model of demyelination, ODC derived demethylated MOG cfDNA was increased in serum and was associated with tissue-wide demyelination, demonstrating the utility of demethylated MOG cfDNA as a biomarker of ODC death. Collected sera from patients with active (symptomatic) relapsing remitting MS (RRMS) demonstrated a higher signature of demethylated MOG cfDNA when compared with patients with inactive disease and healthy controls. Taken together, these results offer a minimally invasive approach to measuring ODC death in the blood of MS patients that may be used to monitor disease progression. PMID- 27381477 TI - Targeting the Ca(2+) Sensor STIM1 by Exosomal Transfer of Ebv-miR-BART13-3p is Associated with Sjogren's Syndrome. AB - Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease that is associated with inflammation and dysfunction of salivary and lacrimal glands. The molecular mechanism(s) underlying this exocrinopathy is not known, although the syndrome has been associated with viruses, such as the Epstein Barr Virus (EBV). We report herein that an EBV-specific microRNA (ebv-miR-BART13-3p) is significantly elevated in salivary glands (SGs) of pSS patients and we show that it targets stromal interacting molecule 1 (STIM1), a primary regulator of the store-operated Ca(2+) entry (SOCE) pathway that is essential for SG function, leading to loss of SOCE and Ca(2+)-dependent activation of NFAT. Although EBV typically infects B cells and not salivary epithelial cells, ebv-miR-BART13-3p is present in both cell types in pSS SGs. Importantly, we further demonstrate that ebv-miR-BART13-3p can be transferred from B cells to salivary epithelial cells through exosomes and it recapitulates its functional effects on calcium signaling in a model system. PMID- 27381478 TI - Health-related quality of life in children with myelomeningocele: a systematic review of the literature. AB - Myelomeningocele (MMC) is the most complex congenital birth defect compatible with life. To provide the best health care for children with MMC, clinicians and researchers have to understand health and functional status of their patients as well as factors influencing their quality of life (QOL). The objective is to review studies that assess health-related quality of life (HRQOL) and determinants of HRQOL in children with MMC. The data sources include MEDLINE, along with reference lists of relevant reviews and included articles. Study eligibility criteria are quantitative studies that assess HRQOL using validated HRQOL instrument. Participants include children aged 0-18 years with diagnosis of MMC or spina bifida. Risk of bias was assessed using the Hayden system for non randomized studies. Narrative synthesis and tables of results of HRQOL studies were conducted. Children with MMC have decreased HRQOL compared with normative population. Physical HRQOL is the most exposed aspect of QOL, while discrepancies in psychosocial domains vary by study. Many determinants of QOL have been found, and it is still not clear which determinant can be described as the strongest predictor. Psychosocial factors are the most consistent determinants of HRQOL.Heterogeneous study sample size, study designs, determinant and outcomes measures limited synthesis of findings. The HRQOL in children with MMC is complex and mediated by a number of associated medical problems, together with a variety of psychosocial and environmental factors. Future research is needed (a) on the relation between complex medical problems, functional independence, parent's and clinician's expectation and HRQOL in children and (b) to assess the differences in HRQOL by social environment and healthcare system. PMID- 27381479 TI - Limbic areas are functionally decoupled and visual cortex takes a more central role during fear conditioning in humans. AB - Going beyond the focus on isolated brain regions (e.g. amygdala), recent neuroimaging studies on fear conditioning point to the relevance of a network of mutually interacting brain regions. In the present MEG study we used Graph Theory to uncover changes in the architecture of the brain functional network shaped by fear conditioning. Firstly, induced power analysis revealed differences in local cortical excitability (lower alpha and beta power) between CS+ and CS- localized to somatosensory cortex and insula. What is more striking however is that the graph theoretical measures unveiled a re-organization of brain functional connections, not evident using conventional power analysis. Subcortical fear related structures exhibited reduced connectivity with temporal and frontal areas rendering the overall brain functional network more sparse during fear conditioning. At the same time, the calcarine took on a more central role in the network. Interestingly, the more the connectivity of limbic areas is reduced, the more central the role of the occipital cortex becomes. We speculated that both, the reduced coupling in some regions and the emerging centrality of others, contribute to the efficient processing of fear-relevant information during fear learning. PMID- 27381480 TI - The biological default state of cell proliferation with variation and motility, a fundamental principle for a theory of organisms. AB - The principle of inertia is central to the modern scientific revolution. By postulating this principle Galileo at once identified a pertinent physical observable (momentum) and a conservation law (momentum conservation). He then could scientifically analyze what modifies inertial movement: gravitation and friction. Inertia, the default state in mechanics, represented a major theoretical commitment: there is no need to explain uniform rectilinear motion, rather, there is a need to explain departures from it. By analogy, we propose a biological default state of proliferation with variation and motility. From this theoretical commitment, what requires explanation is proliferative quiescence, lack of variation, lack of movement. That proliferation is the default state is axiomatic for biologists studying unicellular organisms. Moreover, it is implied in Darwin's "descent with modification". Although a "default state" is a theoretical construct and a limit case that does not need to be instantiated, conditions that closely resemble unrestrained cell proliferation are readily obtained experimentally. We will illustrate theoretical and experimental consequences of applying and of ignoring this principle. PMID- 27381482 TI - Regioselective addition of Grignard reagents to tosylazafulleroid and derivatization to 1,2-disubstituted [60]fullerene. AB - Grignard reagents (RMgBr: R = Et, p-tolyl) selectively attacked the beta-position of the bridgehead double bond of tosylazafulleroid through interaction of Mg with the S[double bond, length as m-dash]O group. The following [5,6] ring closure and C-N bond scission led to aryl/alkyl aminylfullerenes with 1,2-configuration. Tolyl-substituted aminylfullerene was further converted into 1,4-di(p tolyl)fullerene on treatment in acidic toluene. PMID- 27381481 TI - Epilepsy in cerebrovascular diseases: Review of experimental and clinical data with meta-analysis of risk factors. AB - OBJECTIVE: Seizures may occur in close temporal association with a stroke or after a variable interval. Moreover, epilepsy is often encountered in patients with leukoaraiosis. Although early post-stroke seizures have been studied extensively, less attention has been paid to post-stroke epilepsy (PSE) and to epilepsy associated with leukoaraiosis (EAL). The aim of this paper is to review data concerning pathophysiology, prognosis, and treatment of PSE and EAL. METHODS: We performed an extensive literature search to identify experimental and clinical articles on PSE and EAL. We also conducted a systematic review of risk factors for PSE and EAL among eligible studies. RESULTS: PSE is caused by enhanced neuronal excitability within and near the scar. The role played by white matter changes in EAL remains to be elucidated. Meta-analysis showed that cortical involvement (odds ratio [OR] 3.71, 95% confidence interval [CI] 2.34 5.90, p < 0.001), cerebral hemorrhage (OR 2.41, 95% CI 1.57-3.70, p < 0.001), and early seizures (OR 4.43, 95% CI 2.36-8.32, p < 0.001) are associated with an increased risk of PSE. As regards EAL, no prospective, population-based studies evaluated the role of different variables on seizure risk. Studies about the management of PSE are limited. PSE is generally well controlled by drugs. Data about risk factors, prognosis, and treatment of EAL are lacking. SIGNIFICANCE: Pathophysiology and risk factors are well defined for PSE but need to be elucidated for EAL. Management of PSE and EAL relies on the clinician's judgment and should be tailored on an individual basis. PMID- 27381483 TI - Providing end-of-life care in general practice: findings of a national GP questionnaire survey. AB - BACKGROUND: With increasing numbers of people living with complex life-limiting multimorbidity in the community, consideration must be given to improving the organisation and delivery of high-quality palliative and end-of-life care (EOLC). AIM: To provide insight into the experience of GPs providing EOLC in the community, particularly the facilitators and barriers to good-quality care. DESIGN AND SETTING: A web-based national UK questionnaire survey circulated via the Royal College of General Practitioners, NHS, Marie Curie, and Macmillan networks to GPs. METHOD: Responses were analysed using descriptive statistics and an inductive thematic analysis. RESULTS: Responses were received from 516 GPs, who were widely distributed in terms of practice location. Of these, 97% felt that general practice plays a key role in the delivery of care to people approaching the end of life and their families. Four interdependent themes emerged from the data: continuity of care - which can be difficult to achieve because of resource concerns including time, staff numbers, increasing primary care workload, and lack of funding; patient and family factors - with challenges including early identification of palliative care needs and recognition of the end of life, opportunity for care planning discussions, and provision of support for families; medical management - including effective symptom-control and access to specialist palliative care services; and expertise and training - the need for training and professional development was recognised to enhance knowledge, skills, and attitudes towards EOLC. CONCLUSION: The findings reveal enduring priorities for policy, commissioning, practice development, and research in future primary palliative care. PMID- 27381484 TI - Patients' and clinicians' views on the optimum schedules for self-monitoring of blood pressure: a qualitative focus group and interview study. AB - BACKGROUND: Self-monitoring of blood pressure is common but guidance on how it should be carried out varies and it is currently unclear how such guidance is viewed. AIM: To explore patients' and healthcare professionals' (HCPs) views and experiences of the use of different self-monitoring regimens to determine what is acceptable and feasible, and to inform future recommendations. DESIGN AND SETTING: Thirteen focus groups and four HCP interviews were held, with a total of 66 participants (41 patients and 25 HCPs) from primary and secondary care with and without experience of self-monitoring. METHOD: Standard and shortened self monitoring protocols were both considered. Focus groups and interviews were recorded, transcribed verbatim, and analysed using the constant comparative method. RESULTS: Patients generally supported structured schedules but with sufficient flexibility to allow adaptation to individual routine. They preferred a shorter (3-day) schedule to longer (7-day) regimens. Although HCPs could describe benefits for patients of using a schedule, they were reluctant to recommend a specific schedule. Concerns surrounded the use of different schedules for diagnosis and subsequent monitoring. Appropriate education was seen as vital by all participants to enable a self-monitoring schedule to be followed at home. CONCLUSION: There is not a 'one size fits all approach' to developing the optimum protocol from the perspective of users and those implementing it. An approach whereby patients are asked to complete the minimum number of readings required for accurate blood pressure estimation in a flexible manner seems most likely to succeed. Informative advice and guidance should incorporate such flexibility for patients and professionals alike. PMID- 27381485 TI - Nursery sickness policies and their influence on prescribing for conjunctivitis: audit and questionnaire survey. AB - BACKGROUND: Acute infective conjunctivitis is common among preschool children. Public Health England (PHE) recommends that children with conjunctivitis do not need to be excluded from child care, but childcare providers are required to determine their own sickness policies and prior research suggests that children are often excluded until they are treated or have recovered. How the content of these policies impacts on prescribing decisions has not been quantified. AIM: To assess the content of childcare providers' sickness policies and determine the impact they have on clinicians' prescribing. DESIGN AND SETTING: An audit of childcare providers' sickness policies and a questionnaire among primary care clinicians. METHOD: Sickness policies from childcare providers across the UK were compared with PHE guidance. Clinicians completed a questionnaire on the impact that childcare provider policies have on their decision to prescribe antibiotics to preschool children with conjunctivitis. RESULTS: Of 164 policies examined, 86.7% excluded children with conjunctivitis and 49.4% of policies specified a requirement for antibiotics. Two-hundred clinicians completed questionnaires and 42.6% replied that they had been influenced by childcare policies when deciding whether to prescribe antibiotics in this scenario. Furthermore, 15.4% admitted that childcare policies had been the only reason they prescribed antibiotics. CONCLUSION: Most of the childcare providers' sickness policies contain requirements that are inconsistent with PHE guidance. The requirements of childcare sickness policies are likely to be resulting in unnecessary primary care consultations and thousands of prescriptions for antibiotics with little demonstrable clinical or public health benefit. PMID- 27381486 TI - Accounting for multimorbidity in pay for performance: a modelling study using UK Quality and Outcomes Framework data. AB - BACKGROUND: The UK Quality and Outcomes Framework (QOF) offers financial incentives to deliver high-quality care for individual diseases, but the single disease focus takes no account of multimorbidity. AIM: To examine variation in QOF payments for two indicators incentivised in >=1 disease domain. DESIGN AND SETTING: Modelling study using cross-sectional data from 314 general practices in Scotland. METHOD: Maximum payments that practices could receive under existing financial incentives were calculated for blood pressure (BP) control and influenza immunisation according to the number of coexisting clinical conditions. Payments were recalculated assuming a single new indicator. RESULTS: Payment varied by condition (L4.71-L11.08 for one BP control and L2.09-L5.78 for one influenza immunisation). Practices earned more for delivering the same action in patients with multimorbidity: in patients with 2, 3, and >=4 conditions mean payments were L13.95, L21.92, and L29.72 for BP control, and L7.48, L11.21, and L15.14 for influenza immunisation, respectively. Practices in deprived areas had more multiple incentivised patients. When recalculated so that each incentivised action was only paid for once, all practices received less for BP control: affluent practices received more and deprived practices received less for influenza immunisation. CONCLUSION: For patients with single conditions, existing QOF payment methods have more than twofold variation in payment for delivering the same process. Multiple payments were common in patients with multimorbidity. A payment method is required that ensures fairness of rewards while maintaining adequate funding for practices based on actual workload. PMID- 27381487 TI - Out-of-hours primary care use at the end of life: a descriptive study. AB - BACKGROUND: Out-of-hours (OOH) primary care services are integral to the care of patients at end of life. Little is known about the OOH service usage of patients with palliative care needs. AIM: To describe patterns of usage of patients presenting to an OOH service and coded as 'palliative'. DESIGN AND SETTING: A descriptive study of data from the Oxfordshire OOH service. METHOD: A database of all patient contacts with the Oxfordshire OOH service from a 4-year period (June 2010-August 2014) was used to extract demographic and service usage data for all contacts to which clinicians had applied a 'palliative' code. Observed differences in demographic features between palliative and non-palliative contacts were tested using logistic regression. RESULTS: Out of a total of 496 931 contacts, there were 6045 contacts coded palliative; those 'palliative' contacts provided care to 3760 patients. Patients contacting the OOH service with palliative care needs did so predominantly during weekend daytime periods, and over a third had more than one contact. Patients were predictably older than the average population, but contacts coded as 'palliative' were relatively less deprived than contacts to the OOH service for all causes, even after adjusting for age and sex. CONCLUSION: The current 'one-size-fits-most' model of OOH primary care may not allow for the specific needs of patients at the end of life. Wider analysis of palliative patient flow through urgent care services is needed to identify whether healthcare access at the end of life is inequitable, as well as the capacity requirements of a community-based service that can provide high quality end-of-life care. PMID- 27381488 TI - Smartphone App as an aid in the emergency management of avulsed teeth. AB - BACKGROUND/AIM: The initial response by bystanders to an avulsed tooth is a significant factor that can affect its survival and long-term outcome. This study was to assess the knowledge of emergency management of tooth avulsion in a group of schoolteachers and to compare the effects of three different educational interventions. METHODS: Baseline knowledge was assessed using a questionnaire developed for this study. The same questionnaire was used to test changes in the knowledge level following each educational intervention. A convenience sample of elementary and intermediate school teachers (n = 87) participated in this study. Teachers were divided into three groups: Group 1 (Lecture only) was given a 30 min lecture on the emergency management of tooth avulsion. Their knowledge was assessed immediately after the lecture. Group 2 (Lecture and App), the same lecture was given, but participants also had access to a smartphone App, Dental Trauma App (Dental Trauma AB, Linkoping, Sweden), when assessed on their knowledge after the lecture. Group 3 (App), this group was only given the smartphone App to explore and had access to that when being assessed. RESULTS: All three interventions increased the knowledge of tooth avulsion management. A marked increase in the knowledge, regardless of the type of intervention, was observed in the following areas: handling the tooth on the ground (16-96.8%); holding the tooth while being cleansed (19.1-62.5%); and on the best storage medium (10.1-59.3%). Participants using the App only had a significantly higher mean score than participants receiving the lecture only (group 3; P = 0.019) and participants subjected to both Lecture and App (group 1; P = 0.000). CONCLUSION: The Dental Trauma App alone is an effective means of providing accessible knowledge to guide laypeople in managing tooth avulsion, and it can be superior to a lecture-based delivery of information. PMID- 27381489 TI - Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping at 3T MRI of the wrist: Feasibility and clinical application. AB - PURPOSE: To assess the feasibility of delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) and T2 mapping for biochemical imaging of the wrist at 3T. MATERIALS AND METHODS: Seventeen patients with wrist pain (mean age, 41.4 +/- 13.1 years) including a subgroup with chondromalacia (n = 11) and 15 healthy volunteers (26.0 +/- 2.2 years) underwent dGEMRIC and T2 mapping at 3T. For dGEMRIC, the optimum time window after contrast-injection (gadopentetate dimeglumine) was defined as the plateau of the T1 curve of repeated measurements 15-90 minutes postinjection and assessed in all volunteers. Reference values of healthy-appearing cartilage from all individuals and values in areas of chondromalacia were assessed using region-of-interest analyses. Receiver-operating-characteristic analyses were applied to assess discriminatory ability between damaged and normal cartilage. RESULTS: The optimum time window was 45-90 minutes, and the 60-minute timepoint was subsequently used. In chondromalacia, dGEMRIC values were lower (551 +/- 84 msec, P < 0.001), and T2 values higher (63.9 +/- 17.7, P = 0.001) compared to healthy-appearing cartilage of the same patient. Areas under the curve did not significantly differ between dGEMRIC (0.91) and T2 mapping (0.99; P = 0.17). In healthy-appearing cartilage of volunteers and patients, mean dGEMRIC values were 731.3 +/- 47.1 msec and 674.6 +/- 72.1 msec (P = 0.01), and mean T2 values were 36.5 +/- 5 msec and 41.1 +/- 3.2 msec (P = 0.009), respectively. CONCLUSION: At 3T, dGEMRIC and T2 mapping are feasible for biochemical cartilage imaging of the wrist. Both techniques allow separation and biochemical assessment of thin opposing cartilage surfaces and can distinguish between healthy and damaged cartilage. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:381-389. PMID- 27381490 TI - A Mitochondria-Targeted Photosensitizer Showing Improved Photodynamic Therapy Effects Under Hypoxia. AB - Organelle-targeted photosensitizers have been reported to be effective photodynamic therapy (PDT) agents. In this work, we designed and synthesized two iridium(III) complexes that specifically stain the mitochondria and lysosomes of living cells, respectively. Both complexes exhibited long-lived phosphorescence, which is sensitive to oxygen quenching. The photocytotoxicity of the complexes was evaluated under normoxic and hypoxic conditions. The results showed that HeLa cells treated with the mitochondria-targeted complex maintained a slower respiration rate, leading to a higher intracellular oxygen level under hypoxia. As a result, this complex exhibited an improved PDT effect compared to the lysosome-targeted complex, especially under hypoxia conditions, suggestive of a higher practicable potential of mitochondria-targeted PDT agents in cancer therapy. PMID- 27381491 TI - Pelvic recurrence of an ovarian seromucinous borderline tumor detected by vaginal cytology: A case report and review of the literature. AB - Seromucinous borderline tumors are typically confined to the ovaries and rarely relapse after surgery. We report the case of a woman with a seromucinous borderline tumor with peritoneal implant at the Douglas pouch, who was affected by a recurrent tumor at the vaginal stump 2 years and 6 months after the primary surgery. The recurrent lesion was detected by vaginal cytology. Histology of the recurrent lesion showed perineural infiltration, and progression to low-grade adenocarcinoma was suggested. After the second surgery, vaginal cytology showed that the tumor cells remained positive. At postoperative follow-ups of ovarian borderline tumors, an examination of the specific region where recurrence is likely to occur can contribute to the early detection of tumor relapse. Diagn. Cytopathol. 2016;44:912-916. (c) 2016 Wiley Periodicals, Inc. PMID- 27381492 TI - Is it time to rethink the rule of total mesorectal excision? A prospective radiological and pathological study in 49 consecutive patients with mid-rectal cancer. AB - AIM: Total mesorectal excision (TME) after neoadjuvant chemoradiotherapy is the standard treatment for T3-T4 and/or N+ mid-rectal tumours, regardless of the exact tumour level. This leads to optimal oncological results but possible impaired functional results. Reducing rectal excision could reduce the functional drawbacks. This study prospectively assessed the risk of N+ or other mesorectal tumour deposit (OTD) below the tumour level by magnetic resonance imaging (MRI) performed after chemoradiotherapy and pathological examination of the TME specimen. METHOD: Consecutive patients with mid-rectal cancer who underwent TME after chemoradiotherapy were included. A prospective evaluation by postchemoradiotherapy MRI and pathological examination was performed to assess the location of N+ nodes and/or OTDs. RESULTS: Of 49 consecutive patients, 27 (55%) presented with nodes on postchemoradiotherapy MRI. However, only 12 nodes (size 2-4 mm) in 9 patients (18%) were under the tumour level. On pathological examination, 717 total lymph nodes were found, with 37 N+ and 22 OTD. According to the tumour level: (i) above tumour level, 21/453 nodes were N+ and 6 OTD; (ii) at tumour level, 16/166 nodes were N+ and 15 OTD; (iii) below tumour level, 0/98 nodes (0%) was N+ and only 1 OTD (2%) was noted at 2 cm below tumour level. CONCLUSION: After chemoradiotherapy, N+ and/or OTD located under the level of the rectal cancer seems to be a very rare event. A postchemoradiotherapy MRI could help detect such patients. For others patients, conservation of the lower rectum with only a subtotal mesorectal excision could possibly improve function. PMID- 27381493 TI - iRGD-Decorated Polymeric Nanoparticles for the Efficient Delivery of Vandetanib to Hepatocellular Carcinoma: Preparation and in Vitro and in Vivo Evaluation. AB - Molecularly targeted agents that are designed to target specific lesions have been proven effective as clinical cancer therapies; however, most currently available therapeutic agents are poorly water-soluble and require oral administration, thereby resulting in low bioavailability and a high risk of side effects due to dose intensification. The rational engineering of systemically injectable medicines that encapsulate such therapeutic payloads may revolutionize anticancer therapies and remains an under-explored area of drug development. Here, the injectable delivery of a nanomedicine complexed with an oral multitargeted kinase inhibitor, vandetanib (vanib), was explored using polymeric nanoparticles (NPs) to achieve the selective accumulation of drug payloads within tumor lesions. To demonstrate this concept, we used biodegradable amphiphilic block copolymer poly(ethylene glycol)-block-poly(D, L-lactic acid) (PEG-PLA) to nanoprecipitate this potent agent to form water-soluble NPs that are suitable for intravenous administration. NP-vanib induced cytotoxic activity by inhibiting the angiogenetic events mediated by VEGFR and EGFR kinases in tested cancer cells and inhibited the growth, tube formation and metastasis of HUVECs. The intravenously injection of NP-vanib into mice bearing HCC BEL-7402 xenografts more effectively inhibited the tumor than the oral administration of vanib. In addition, due to the modular design of these NPs, the drug-loaded particles can easily be decorated with iRGD, a tumor-homing and -penetrating peptide motif, which further improved the in vivo performance of these vanib-loaded NPs. Our results demonstrate that reformulating targeted therapeutic agents in NPs permits their systemic administration and thus significantly improves the potency of currently available, orally delivered agents. PMID- 27381495 TI - Editorial: Is technology responsible for nurses losing touch? PMID- 27381496 TI - Enhanced base excision repair capacity in carotid atherosclerosis may protect nuclear DNA but not mitochondrial DNA. AB - BACKGROUND: Lesional and systemic oxidative stress has been implicated in the pathogenesis of atherosclerosis, potentially leading to accumulation of DNA base lesions within atherosclerotic plaques. Although base excision repair (BER) is a major pathway counteracting oxidative DNA damage, our knowledge on BER and accumulation of DNA base lesions in clinical atherosclerosis is scarce. Here, we evaluated the transcriptional profile of a wide spectrum of BER components as well as DNA damage accumulation in atherosclerotic and non-atherosclerotic arteries. METHODS: BER gene expression levels were analyzed in 162 carotid plaques, 8 disease-free carotid specimens from patients with carotid plaques and 10 non-atherosclerotic control arteries. Genomic integrity, mitochondrial (mt) DNA copy number, oxidative DNA damage and BER proteins were evaluated in a subgroup of plaques and controls. RESULTS: Our major findings were: (i) The BER pathway showed a global increased transcriptional response in plaques as compared to control arteries, accompanied by increased expression of several BER proteins. (ii) Whereas nuclear DNA stability was maintained within carotid plaques, mtDNA integrity and copy number were decreased. (iii) Within carotid plaques, mRNA levels of several BER genes correlated with macrophage markers. (iv) In vitro, some of the BER genes were highly expressed in the anti-inflammatory and pro resolving M2 macrophages, showing increased expression upon exposure to modified lipids. CONCLUSIONS: The increased transcriptional response of BER genes in atherosclerosis may contribute to lesional nuclear DNA stability but appears insufficient to maintain mtDNA integrity, potentially influencing mitochondrial function in cells within the atherosclerotic lesion. PMID- 27381494 TI - A place for precision medicine in bladder cancer: targeting the FGFRs. AB - Bladder tumors show diverse molecular features and clinical outcome. Muscle invasive bladder cancer has poor prognosis and novel approaches to systemic therapy are urgently required. Non-muscle-invasive bladder cancer has good prognosis, but high recurrence rate and the requirement for life-long disease monitoring places a major burden on patients and healthcare providers. Studies of tumor tissues from both disease groups have identified frequent alterations of FGFRs, including mutations of FGFR3 and dysregulated expression of FGFR1 and FGFR3 that suggest that these may be valid therapeutic targets. We summarize current understanding of the molecular alterations affecting these receptors in bladder tumors, preclinical studies validating them as therapeutic targets, available FGFR-targeted agents and results from early clinical trials in bladder cancer patients. PMID- 27381498 TI - Level of HE4 is Correlated with Diagnosis of Struma Ovarii: A Case Report. AB - BACKGROUND Struma ovarii is a rare ovarian teratoma with non-specific clinical presentation that can mimic malignancy, especially when combined with the presence of ascites. Since the surgical procedures performed for benign and malignant tumors are quite different, pre-operative differential diagnosis is key. In this case report we compare the levels of biomarkers CA 125 and HE4 in the differential diagnosis of a suspicious ovarian tumor. CASE REPORT A 75-year old woman with a palpable mass at the left adnexa, ascites, and high levels of CA 125, underwent a subtotal abdominal hysterectomy and bilateral salpingo oophorectomy. Histology reported benign struma ovarii. CONCLUSIONS Even though transvaginal ultrasound and CA 125 levels suggested malignancy, HE4 measurements correctly diagnosed benignity. PMID- 27381497 TI - NEDDylation promotes stress granule assembly. AB - Stress granules (SGs) harbour translationally stalled messenger ribonucleoproteins and play important roles in regulating gene expression and cell fate. Here we show that neddylation promotes SG assembly in response to arsenite-induced oxidative stress. Inhibition or depletion of key components of the neddylation machinery concomitantly inhibits stress-induced polysome disassembly and SG assembly. Affinity purification and subsequent mass spectrometric analysis of Nedd8-conjugated proteins from translationally stalled ribosomal fractions identified ribosomal proteins, translation factors and RNA binding proteins (RBPs), including SRSF3, a previously known SG regulator. We show that SRSF3 is selectively neddylated at Lys85 in response to arsenite. A non neddylatable SRSF3 (K85R) mutant do not prevent arsenite-induced polysome disassembly, but fails to support the SG assembly, suggesting that the neddylation pathway plays an important role in SG assembly. PMID- 27381499 TI - A new shoulder model with a biologically inspired glenohumeral joint. AB - Kinematically unconstrained biomechanical models of the glenohumeral (GH) joint are needed to study the GH joint function, especially the mechanisms of joint stability. The purpose of this study is to develop a large-scale multibody model of the upper limb that simulates the 6 degrees of freedom (DOF) of the GH joint and to propose a novel inverse dynamics procedure that allows the evaluation of not only the muscle and joint reaction forces of the upper limb but also the GH joint translations. The biomechanical model developed is composed of 7 rigid bodies, constrained by 6 anatomical joints, and acted upon by 21 muscles. The GH joint is described as a spherical joint with clearance. Assuming that the GH joint translates according to the muscle load distribution, the redundant muscle load sharing problem is formulated considering as design variables the 3 translational coordinates associated with the GH joint translations, the joint reaction forces associated with the remaining kinematic constraints, and the muscle activations. For the abduction motion in the frontal plane analysed, the muscle and joint reaction forces estimated by the new biomechanical model proposed are similar to those estimated by a model in which the GH joint is modeled as an ideal spherical joint. Even though this result supports the assumption of an ideal GH joint to study the muscle load sharing problem, only a 6 DOF model of the GH joint, as the one proposed here, provides information regarding the joint translations. In this study, the biomechanical model developed predicts an initial upward and posterior migration of the humeral head, followed by an inferior and anterior movement, which is in good agreement with the literature. PMID- 27381501 TI - Fabrication and multifunctional properties of ultrasmall water-soluble tungsten oxide quantum dots. AB - A facile and green method has been demonstrated to synthesize ultrasmall tungsten oxide quantum dots (WOx QDs). The water-soluble WOx QDs present high luminescence stability, strong peroxidase-like activity, and excellent electrochemiluminescence properties. This work provides an eco-friendly strategy to prepare multifunctional WOx QDs, and opens the door for bioapplications of the WOx QDs. PMID- 27381500 TI - Modelling survival: exposure pattern, species sensitivity and uncertainty. AB - The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates to build species sensitivity distributions for different exposure patterns. We find that GUTS adequately predicts survival across exposure patterns that vary over time. When toxicity is assessed for time variable concentrations species may differ in their responses depending on the exposure profile. This can result in different species sensitivity rankings and safe levels. The interplay of exposure pattern and species sensitivity deserves systematic investigation in order to better understand how organisms respond to stress, including humans. PMID- 27381503 TI - Effect of non-steroidal anti-inflammatory drugs on biological properties of Acanthamoeba castellanii belonging to the T4 genotype. AB - Non-steroidal anti-inflammatory drug, Diclofenac, targeting COX have shown promise in the treatment of Acanthamoeba keratitis, but the underlying mechanisms remain unknown. Using various NSAIDs, Diclofenac sodium, Indomethacin, and Acetaminophen, here we determined the effects of NSAIDs on the biological properties of Acanthamoeba castellanii belonging to the T4 genotype. Using amoebicidal assays, the results revealed that Diclofenac sodium, and Indomethacin affected growth of A. castellanii. In contrast, none of the compounds tested had any effect on the viability of A. castellanii. Importantly, all NSAIDs tested abolished A. castellanii encystation. This is a significant finding as the ability of amoebae to transform into the dormant cyst form presents a significant challenge in the successful treatment of infection. The NSAIDs inhibit production of cyclo-oxegenase, which regulates the synthesis of prostaglandins suggesting that cyclooxygenases (COX-1 and COX-2) and prostaglandins play significant role(s) in Acanthamoeba biology. As NSAIDs are routinely used in the clinical practice, these findings may help design improved preventative strategies and/or of therapeutic value to improve prognosis, when used in combination with other anti-amoebic drugs. PMID- 27381504 TI - Effects of electroacupuncture in a mouse model of fibromyalgia: role of N-methyl D-aspartate receptors and related mechanisms. AB - OBJECTIVE: N-methyl-D-aspartate receptor (NMDAR) activation and downstream transduction pathways are crucial for pain signalling. Fibromyalgia (FM) is a common pain syndrome of unclear aetiology that is often drug-refractory but may benefit from treatment with electroacupuncture (EA). We examined the contributions of NMDAR signalling to FM pain and EA responses in a mouse model. METHODS: A model of FM was established by acid saline injection in 32 mice and subgroups (n=8 each) were treated with EA (2 Hz, 15 min daily for 4 days) or minimal acupuncture (MA). Expression of NMDAR subunits, calmodulin-dependent protein kinase II (CaMKII), cyclic AMP response element binding protein (pCREB) and their corresponding phospho-activated forms were measured by Western blotting and immunohistochemistry. RESULTS: Acid saline injection induced significant mechanical hyperalgesia (paw withdrawal threshold 2.18+/-0.27 g, p<0.05 vs controls), which was reversed by EA (4.23+/-0.33 g, p<0.05 vs FM group) but not by MA (2.37+/-0.14 g, p<0.05 vs EA group). Expression levels of phosphorylated N methyl-D-aspartate receptor (pNR)1 and pNR2B were significantly increased in the dorsal root ganglion of FM model mice (132.21+/-14.4% and 116.69+/-3.22% of control values), whereas NR1 and NR2B levels were unchanged (97.31+/-3.79% and 97.07%+/-2.27%, respectively). Expression levels of pCaMKIIalpha and pCREB were also higher in the FM group, and these changes were reversed by EA but not by MA. Similar changes in expression were observed in spinal cord neurons. CONCLUSIONS: Reduced NMDAR-CaMKIIalpha-pCREB signalling is implicated in the positive effects of EA in FM. NMDAR signalling components may represent promising therapeutic targets for FM treatment. PMID- 27381505 TI - Interaction of resistance training, electroacupuncture and Huang Qi supplementation on skeletal muscle function and GLUT4 protein concentration in rats. AB - OBJECTIVE: To determine the effects and potential synergy of resistance training (RT), Huang Qi (HQ) herbal supplementation, and electroacupuncture (EA) on skeletal muscle mass, contractile properties, and components of the insulin signalling pathway in healthy Sprague Dawley rats. METHODS: Female Sprague Dawley rats were randomly assigned to one of five groups (n=8 each): control (CON), RT only, RT with EA (RT-EA), RT with HQ (RT-HQ), and RT combined with both EA and HQ (RT-EA-HQ). RT was performed using ladder climbing every other day for 8 weeks. Sparse-wave EA was applied for 15 min/day, 3 times/week for 8 weeks. HQ supplementation was provided via oral gavage daily for 8 weeks. RESULTS: RT significantly increased the muscle mass of the flexor hallucis longus (FHL) compared to CON. The isometric twitch and tetanic tension of the FHL in the RT EA, RT-HQ, and RT-EA-HQ groups were significantly higher compared to CON and RT groups. RT-EA treatment (with or without HQ) significantly increased GLUT4 protein concentration but had no impact on Akt-2. CONCLUSIONS: EA appears to be an effective treatment modality for increasing muscle mass and function when combined with RT. RT-EA may also be an effective method for improving glucose tolerance as a result of increases in GLUT4 protein concentration. PMID- 27381506 TI - Microblogging as an extension of science reporting. AB - Mass media have long provided general publics with science news. New media such as Twitter have entered this system and provide an additional platform for the dissemination of science information. Based on automated collection and analysis of >900 news articles and 70,000 tweets, this study explores the online communication of current science news. Topic modeling (latent Dirichlet allocation) was used to extract five broad themes of science reporting: space missions, the US government shutdown, cancer research, Nobel Prizes, and climate change. Using content and network analysis, Twitter was found to extend public science communication by providing additional voices and contextualizations of science issues. It serves a recommender role by linking to web resources, connecting users, and directing users' attention. This article suggests that microblogging adds a new and relevant layer to the public communication of science. PMID- 27381508 TI - Is transthyretin a good marker of nutritional status? AB - The assay of plasma transthyretin (TTR), also known as prealbumin, is a key step in the assessment of nutritional status. However, it remains unclear whether it really is a useful nutrition marker, and when and how to use it and interpret TTR levels and variations. Risk of malnutrition, malnutrition severity, prognosis associated with malnutrition and effectiveness of refeeding are four parameters in nutritional assessment, and need clear separation to understand the associated utility of TTR. TTR does not have the same impact and potential on each of these parameters: it can be helpful but not essential for evaluating the risk of malnutrition, and it can diagnose malnutrition and its severity in patients with no inflammation syndrome. TTR is a good marker for prognosis associated with malnutrition, and is even better for monitoring refeeding efficacy despite inflammation. Thresholds depend on the purpose for which it is used. We propose a simple algorithm to guide the interpretation of TTR levels as a helpful tool for day-to-day practice. PMID- 27381507 TI - Evaluation of a high nutritional quality snack based on oat flakes and inulin: effects on postprandial glucose, insulin and ghrelin responses of healthy subjects. AB - The consumption of high nutritional value snacks may favorably affect the diet quality. Biscuits manufactured with oat flakes and maltitol were assessed for glycemic, insulinemic and ghrelin responses. Enrichment with inulin, a fructooligosachararide (FOS) which acts as soluble fiber, was performed in an attempt to further increase the dietary fiber content and examine potential additional postprandial benefits. Eleven healthy subjects participated in the study and consumed either 80 g oat biscuits (OB) or 81 g oat biscuits with 4% inulin (OBIN) or a solution containing 50 g of glucose (reference food), each yielding 50 g of available carbohydrates. Venous blood samples were collected before consumption and at 15, 30, 45, 60, 90, 120 and 180 min postprandially. The developed products were also evaluated for physicochemical properties, including porosity, density, texture, color, sensory attributes and microstructure (by scanning electron microscopy). Both biscuits demonstrated a low glycemic index (GI), which was found to be 32.82 +/- 8.07 for OB and 45.68 +/- 9.64 for OBIN. Compared to OB, OBIN demonstrated higher insulin response at 45 and 60 min and higher ghrelin suppression at 60 and 120 min postprandially (P < 0.05). Furthermore, OBIN demonstrated increased hardness and color values, lower porosity, and higher rate of starch granule gelatinization, without significantly altering the sensory attributes. Biscuits formulated with oat flakes and maltitol with or without 4% inulin can be classified as low GI foods. Inulin addition significantly lowered the ghrelin response to OBIN, suggesting an advantage of OBIN in the modulation of satiety; however, no further benefits regarding glucose and insulin responses were observed. PMID- 27381509 TI - R521C and R521H mutations in FUS result in weak binding with Karyopherinbeta2 leading to Amyotrophic lateral sclerosis: a molecular docking and dynamics study. AB - Fused in sarcoma (FUS) gene encodes the RNA binding protein FUS. This gene is mapped to chromosome 16p11.2. The FUS protein binds with karyopherinebeta2 (Kapbeta2) through its proline/tyrosine nuclear localization signal (PY-NLS) that helps in the localization of FUS protein within the nucleus. Arginine residue in 521 position (R521) of PY-NLS plays a vital role in the binding of FUS protein with Kapbeta2. Mutations in this position (R521C and R521H) are the most predominant mutations associated with amyotrophic lateral sclerosis (ALS). However, the mechanism by which these mutations lead to ALS is poorly understood. We examined the binding behaviour of the mutants FUS (R521C) and FUS (R521H) with Kapbeta2 through protein-protein docking and molecular dynamics simulation. The binding patterns of mutants were compared with the binding behaviour of wild FUS Kapbeta2. Our results suggest that these mutants have relatively weak binding affinity with Kapbeta2 when compared with wild FUS-Kapbeta2 as indicated by the lesser number of interactions found between the mutant FUS and Kapbeta2. Hence, these mutations weakens the binding and this results in the cytoplasmic mislocalization of mutant FUS; and thereby it increases the severity of ALS. PMID- 27381510 TI - Microbial biotransformation of DON: molecular basis for reduced toxicity. AB - Bacteria are able to de-epoxidize or epimerize deoxynivalenol (DON), a mycotoxin, to deepoxy-deoxynivalenol (deepoxy-DON or DOM-1) or 3-epi-deoxynivalenol (3-epi DON), respectively. Using different approaches, the intestinal toxicity of 3 molecules was compared and the molecular basis for the reduced toxicity investigated. In human intestinal epithelial cells, deepoxy-DON and 3-epi-DON were not cytotoxic, did not change the oxygen consumption or impair the barrier function. In intestinal explants, exposure for 4 hours to 10 MUM DON induced intestinal lesions not seen in explants treated with deepoxy-DON and 3-epi-DON. A pan-genomic transcriptomic analysis was performed on intestinal explants. 747 probes, representing 323 genes, were differentially expressed, between DON treated and control explants. By contrast, no differentially expressed genes were observed between control, deepoxy-DON and 3-epi-DON treated explants. Both DON and its biotransformation products were able to fit into the pockets of the A site of the ribosome peptidyl transferase center. DON forms three hydrogen bonds with the A site and activates MAPKinases (mitogen-activated protein kinases). By contrast deepoxy-DON and 3-epi-DON only form two hydrogen bonds and do not activate MAPKinases. Our data demonstrate that bacterial de-epoxidation or epimerization of DON altered their interaction with the ribosome, leading to an absence of MAPKinase activation and a reduced toxicity. PMID- 27381511 TI - Quantum memristors. AB - Technology based on memristors, resistors with memory whose resistance depends on the history of the crossing charges, has lately enhanced the classical paradigm of computation with neuromorphic architectures. However, in contrast to the known quantized models of passive circuit elements, such as inductors, capacitors or resistors, the design and realization of a quantum memristor is still missing. Here, we introduce the concept of a quantum memristor as a quantum dissipative device, whose decoherence mechanism is controlled by a continuous-measurement feedback scheme, which accounts for the memory. Indeed, we provide numerical simulations showing that memory effects actually persist in the quantum regime. Our quantization method, specifically designed for superconducting circuits, may be extended to other quantum platforms, allowing for memristor-type constructions in different quantum technologies. The proposed quantum memristor is then a building block for neuromorphic quantum computation and quantum simulations of non-Markovian systems. PMID- 27381513 TI - Deliberate Design of TiO2 Nanostructures towards Superior Photovoltaic Cells. AB - TiO2 nanostructures are being sought after as flexibly utilizable building blocks for the fabrication of the mesoporous thin-film photoelectrodes that are the heart of the third-generation photovoltaic devices, such as dye-sensitized solar cells (DSSCs), quantum-dot-sensitized solar cells (QDSSCs), and the recently promoted perovskite-type solar cells. Here, we report deliberate tailoring of TiO2 nanostructures for superior photovoltaic cells. Morphology engineering of TiO2 nanostructures is realized by designing synthetic protocols in which the precursor hydrolysis, crystal growth, and oligomer self-organization are precisely controlled. TiO2 nanostructures in forms varying from isolated nanocubes, nanorods, and cross-linked nanorods to complex hierarchical structures and shape-defined mesoporous micro-/nanostructures were successfully synthesized. The photoanodes made from the shape-defined mesoporous TiO2 microspheres and nanospindles presented superior performances, owing to the well-defined overall shapes and the inner ordered nanochannels, which allow not only a high amount of dye uptake, but also improved visible-light absorption. This study provides a new way to seek an optimal synthetic protocol to meet the required functionality of the nanomaterials. PMID- 27381512 TI - Early articular cartilage MRI T2 changes after anterior cruciate ligament reconstruction correlate with later changes in T2 and cartilage thickness. AB - : Anterior cruciate ligament (ACL) injury is a known risk factor for future development of osteoarthritis (OA). This human clinical study seeks to determine if early changes to cartilage MRI T2 maps between baseline and 6 months following ACL reconstruction (ACLR) are associated with changes to cartilage T2 and cartilage thickness between baseline and 2 years after ACLR. Changes to T2 texture metrics and T2 mean values in medial knee cartilage of 17 human subjects 6 months after ACLR were compared to 2-year changes in T2 and in cartilage thickness of the same areas. T2 texture and mean assessments were also compared to that of 11 uninjured controls. In ACLR subjects, six-month changes in mean T2 correlated to 2-year changes in mean T2 (R = 0.80, p = 0.0001), and 6-month changes to T2 texture metrics, but not T2 mean, correlated with 2-year changes in medial femoral cartilage thickness in 9 of the 20 texture features assessed (R = 0.48-0.72, p <= 0.05). Both mean T2 and texture differed (p < 0.05) between ALCR subjects and uninjured controls. CLINICAL SIGNIFICANCE: These results show that short-term longitudinal evaluation of T2 map and textural changes may provide early warning of cartilage at risk for progressive degeneration after ACL injury and reconstruction. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:699-706, 2017. PMID- 27381514 TI - Locomotor preferences in terrestrial vertebrates: An online crowdsourcing approach to data collection. AB - Understanding how animals move within their environment is a burgeoning field of research. Despite this, relatively basic data, such as the locomotor speeds that animals choose to walk at in the wild, are sparse. If animals choose to walk with dynamic similarity, they will move at equal dimensionless speeds, represented by Froude number (Fr). Fr may be interpreted from simple limb kinematics obtained from video data. Here, using Internet videos, limb kinematics were measured in 112 bird and mammal species weighing between 0.61 and 5400 kg. This novel method of data collection enabled the determination of kinematics for animals walking at their self-selected speeds without the need for exhaustive fieldwork. At larger sizes, both birds and mammals prefer to walk at slower relative speeds and relative stride frequencies, as preferred Fr decreased in larger species, indicating that Fr may not be a good predictor of preferred locomotor speeds. This may result from the observation that the minimum cost of transport is approached at lower Fr in larger species. Birds walk with higher duty factors, lower stride frequencies and longer stance times compared to mammals at self selected speeds. The trend towards lower preferred Fr is also apparent in extinct vertebrate species. PMID- 27381515 TI - Noninvasive detection of gastric cancer. AB - Gastric cancer (GC) is the fifth most common cancer and the third common cause of cancer death worldwide. Endoscopy is the most effective method for GC screening, but its application is limited by the invasion. Therefore, continuous efforts have been made to develop noninvasive methods for GC detection and promising results have been reported. Here, we review the advances in GC detection by protein and nucleic acid tumor markers, circulating tumor cells, and tumor associated autoantibodies in peripheral blood. Some potential new noninvasive methods for GC detection are also reviewed, including exhaled breath analysis, blood spectroscopy analysis and molecular imaging. PMID- 27381520 TI - Identification and biological activity of ogipeptins, novel LPS inhibitors produced by marine bacterium. AB - A library of secondary metabolites from microorganisms was screened to identify novel inhibitors against lipopolysaccharide (LPS), a strong stimulant of innate immunity. Novel cyclic peptides, ogipeptin A, B, C and D, were identified in the culture broth of the marine bacterium Pseudoalteromonas sp. SANK 71903. These compounds blocked LPS binding to the cluster of differentiation 14 (CD14) in vitro with IC50 values of 4.8, 6.0, 4.1 and 5.6 nm, respectively, and attenuated tumor necrosis factor-alpha secretion from LPS-stimulated macrophage-like cells. These compounds also displayed antimicrobial activity against Escherichia coli with minimum inhibitory concentrations ranging from 0.25 MUg ml-1 to 1 MUg ml-1. Thus, novel antibiotics that inhibited LPS-induced innate immune reactions were identified in this study. PMID- 27381521 TI - Antibiotic combinations for controlling colistin-resistant Enterobacter cloacae. AB - Enterobacter cloacae is a Gram-negative bacterium associated with high morbidity and mortality in intensive care patients due to its resistance to multiple antibiotics. Currently, therapy against multi-resistant bacteria consists of using colistin, in spite of its toxic effects at higher concentrations. In this context, colistin-resistant E. cloacae strains were challenged with lower levels of colistin combined with other antibiotics to reduce colistin-associated side effects. Colistin-resistant E. cloacae (ATCC 49141) strains were generated by serial propagation in subinhibitory colistin concentrations. After this, three colistin-resistant and three nonresistant replicates were isolated. The identity of all the strains was confirmed by MALDI-TOF MS, VITEK 2 and MicroScan analysis. Furthermore, cross-resistance to other antibiotics was checked by disk diffusion and automated systems. The synergistic effects of the combined use of colistin and chloramphenicol were observed via the broth microdilution checkerboard method. First, data here reported showed that all strains presented intrinsic resistance to penicillin, cephalosporin (except fourth generation), monobactam, and some associations of penicillin and beta-lactamase inhibitors. Moreover, a chloramphenicol and colistin combination was capable of inhibiting the induced colistin-resistant strains as well as two colistin-resistant clinical strains. Furthermore, no cytotoxic effect was observed by using such concentrations. In summary, the data reported here showed for the first time the possible therapeutic use of colistin-chloramphenicol for infections caused by colistin resistant E. cloacae. PMID- 27381523 TI - Flagellin based biomimetic coatings: From cell-repellent surfaces to highly adhesive coatings. AB - Biomimetic coatings with cell-adhesion-regulating functionalities are intensively researched today. For example, cell-based biosensing for drug development, biomedical implants, and tissue engineering require that the surface adhesion of living cells is well controlled. Recently, we have shown that the bacterial flagellar protein, flagellin, adsorbs through its terminal segments to hydrophobic surfaces, forming an oriented monolayer and exposing its variable D3 domain to the solution. Here, we hypothesized that this nanostructured layer is highly cell-repellent since it mimics the surface of the flagellar filaments. Moreover, we proposed flagellin as a carrier molecule to display the cell adhesive RGD (Arg-Gly-Asp) peptide sequence and induce cell adhesion on the coated surface. The D3 domain of flagellin was replaced with one or more RGD motifs linked by various oligopeptides modulating flexibility and accessibility of the inserted segment. The obtained flagellin variants were applied to create surface coatings inducing cell adhesion and spreading to different levels, while wild-type flagellin was shown to form a surface layer with strong anti-adhesive properties. As reference surfaces synthetic polymers were applied which have anti adhesive (PLL-g-PEG poly(l-lysine)-graft-poly(ethylene glycol)) or adhesion inducing properties (RGD-functionalized PLL-g-PEG). Quantitative adhesion data was obtained by employing optical biochips and microscopy. Cell-adhesion regulating coatings can be simply formed on hydrophobic surfaces by using the developed flagellin-based constructs. The developed novel RGD-displaying flagellin variants can be easily obtained by bacterial production and can serve as alternatives to create cell-adhesion-regulating biomimetic coatings. STATEMENT OF SIGNIFICANCE: In the present work, we show for the first time that. PMID- 27381524 TI - Diversification and enrichment of clinical biomaterials inspired by Darwinian evolution. AB - Regenerative medicine and biomaterials design are driven by biomimicry. There is the essential requirement to emulate human cell, tissue, organ and physiological complexity to ensure long-lasting clinical success. Biomimicry projects for biomaterials innovation can be re-invigorated with evolutionary insights and perspectives, since Darwinian evolution is the original dynamic process for biological organisation and complexity. Many existing human inspired regenerative biomaterials (defined as a nature generated, nature derived and nature mimicking structure, produced within a biological system, which can deputise for, or replace human tissues for which it closely matches) are without important elements of biological complexity such as, hierarchy and autonomous actions. It is possible to engineer these essential elements into clinical biomaterials via bioinspired implementation of concepts, processes and mechanisms played out during Darwinian evolution; mechanisms such as, directed, computational, accelerated evolutions and artificial selection contrived in the laboratory. These dynamos for innovation can be used during biomaterials fabrication, but also to choose optimal designs in the regeneration process. Further evolutionary information can help at the design stage; gleaned from the historical evolution of material adaptations compared across phylogenies to changes in their environment and habitats. Taken together, harnessing evolutionary mechanisms and evolutionary pathways, leading to ideal adaptations, will eventually provide a new class of Darwinian and evolutionary biomaterials. This will provide bioengineers with a more diversified and more efficient innovation tool for biomaterial design, synthesis and function than currently achieved with synthetic materials chemistry programmes and rational based materials design approach, which require reasoned logic. It will also inject further creativity, diversity and richness into the biomedical technologies that we make. All of which are based on biological principles. Such evolution-inspired biomaterials have the potential to generate innovative solutions, which match with existing bioengineering problems, in vital areas of clinical materials translation that include tissue engineering, gene delivery, drug delivery, immunity modulation, and scar-less wound healing. STATEMENT OF SIGNIFICANCE: Evolution by natural selection is a powerful generator of innovations in molecular, materials and structures. Man has influenced evolution for thousands of years, to create new breeds of farm animals and crop plants, but now molecular and materials can be molded in the same way. Biological molecules and simple structures can be evolved, literally in the laboratory. Furthermore, they are re-designed via lessons learnt from evolutionary history. Through a 3-step process to (1) create variants in material building blocks, (2) screen the variants with beneficial traits/properties and (3) select and support their self-assembly into usable materials, improvements in design and performance can emerge. By introducing biological molecules and small organisms into this process, it is possible to make increasingly diversified, sophisticated and clinically relevant materials for multiple roles in biomedicine. PMID- 27381522 TI - Insights into microbial cryptic gene activation and strain improvement: principle, application and technical aspects. AB - As bacteria and fungi have been found to contain genes encoding enzymes that synthesize a plethora of potential secondary metabolites, interest has grown in the activation of these cryptic pathways. Homologous and heterologous expression of these cryptic secondary metabolite-biosynthetic genes, often silent under ordinary laboratory fermentation conditions, may lead to the discovery of novel secondary metabolites. This review addresses current progress in the activation of these pathways, describing methods for activating silent genes. It especially focuses on genetic manipulation of transcription and translation (ribosome engineering), the utilization of elicitors, metabolism remodeling and co cultivation. In particular, the principles and technical points of ribosome engineering and the significance of S-adenosylmethionine in bacterial physiology, especially secondary metabolism, are described in detail. PMID- 27381525 TI - Syndecan-4 enhances PDGF-BB activity in diabetic wound healing. AB - Non-healing ulcers are a common consequence of long-term diabetes and severe peripheral vascular disease. These non-healing wounds are a major source of morbidity in patients with diabetes and place a heavy financial burden on the healthcare system. Growth factor therapies are an attractive strategy for enhancing wound closure in non-healing wounds but have only achieved mixed results in clinical trials. Platelet derived growth factor-BB (PDGF-BB) is the only currently approved growth factor therapy for non-healing wounds. However, PDGF-BB therapy is not effective in many patients and requires high doses that increase the potential for side effects. In this work, we demonstrate that syndecan-4 delivered in a proteoliposomal formulation enhances PDGF-BB activity in diabetic wound healing. In particular, syndecan-4 proteoliposomes enhance the migration of keratinocytes derived from patients with diabetes. In addition, syndecan-4 proteoliposomes sensitize keratinocytes to PDGF-BB stimulation, enhancing the intracellular signaling response to PDGF-BB. We further demonstrated that co-therapy with syndecan-4 proteoliposomes enhanced wound closure in diabetic, hyperlipidemic ob/ob mice. Wounds treated with both syndecan 4 proteoliposomes and PDGF-BB had increased re-epithelization and angiogenesis in comparison to wounds treated with PDGF-BB alone. Moreover, the wounds treated with syndecan-4 proteoliposomes and PDGF-BB also had increased M2 macrophages and reduced M1 macrophages, suggesting syndecan-4 delivery induces immunomodulation within the healing wounds. Together our findings support that syndecan-4 proteoliposomes markedly improve PDGF-BB efficacy for wound healing and may be useful in enhancing treatments for non-healing wounds. STATEMENT OF SIGNIFICANCE: Non-healing wounds are major healthcare issue for patients with diabetes and peripheral vascular disease. Growth factor therapies have potential for healing chronic wounds but have not been effective for many patients. PDGF-BB is currently the only approved growth factor for enhancing wound healing. However, it has not seen widespread adoption due to limited efficacy and high cost. In this work, we have developed an enhancing agent that improves the activity of PDGF-BB in promoting wound healing in animals with diabetes. This co-therapy may be useful in improving the efficacy of PDGFBB and enhance its safety through lowering the dose of growth factor needed to improve wound healing. PMID- 27381526 TI - The macula in pediatric glaucoma: quantifying the inner and outer layers via optical coherence tomography automatic segmentation. AB - BACKGROUND: Recent Spectralis (Heidelberg, Germany) spectral domain optical coherence tomography (SD-OCT) research software can automatically quantify the thickness of each individual retinal layer. The macular ganglion cell layer (GCL) and ganglion cell complex may be more sensitive for detecting glaucoma than the peripapillary retinal nerve fiber layer (pRNFL). The aim of this study was to characterize and compare the volume of each macular layer in the eyes of children with glaucoma versus those of normal controls. METHODS: The medical records of children with primary glaucoma and physiologic cupping who had undergone Spectralis SD-OCT imaging of the macula and pRNFL were reviewed retrospectively. Controls were recruited from a separate prospective study. Children with refractive error of <+/-5 or retinal or neurologic abnormalities were excluded. The average volume of each of the 8 retinal layers in the macula (central 6 mm) and pRNFL were compared among diagnostic groups. RESULTS: A total of 80 eyes of 80 children were included: 37 glaucoma eyes (25 with primary congenital and 12 with juvenile open-angle glaucoma) and 43 nonglaucoma eyes (28 with physiologic cupping). Eyes with glaucoma had significantly thinner mean macular nerve fiber layers, ganglion cell layers, inner plexiform layers, and pRNFLs than nonglaucomatous eyes: 0.82 +/- 0.24 MUm versus 1.00 +/- 0.12 MUm; 0.93 +/- 0.22 MUm versus 1.13 +/- 0.10 MUm; 0.80 +/- 0.14 MUm versus 0.91 +/- 0.07 MUm; 81.6 +/ 26.5 MUm versus 102.7 +/- 10.0 MUm, respectively (P < 0.00556 for all). Eyes without cupping and those with physiologic cupping were equivalent for all variables tested. CONCLUSIONS: Children with glaucoma have thinning of the three innermost retinal macular layers. PMID- 27381527 TI - Type 4 Duane syndrome. AB - PURPOSE: To identify cases of synergistic divergence whose characteristics suggest that this entity is a form of Duane syndrome. METHODS: The records of all patients with a Duane syndrome diagnosis, including standardized eye position photographs, from the E-Consultation program of Cybersight, Orbis International were analyzed. RESULTS: A total of 350 Duane syndrome cases were identified. Of these, 19 (5%) had features consistent with synergistic divergence, or type 4 Duane syndrome. Of the 19, 16 (84%) were male, 15 (79%) had palpebral fissure narrowing, all had anomalous head posture, and 18 (95%) were exotropic. Only 9 (47%) patients were reported to have undergone surgery. CONCLUSIONS: Synergistic divergence is a rare entity with features similar to those of Duane syndrome. We suggest that this entity be classified as type 4 Duane syndrome, because it has unique findings and an innervation pattern that differs from the other 3 recognized types. PMID- 27381528 TI - Childhood esotropia: child and parent concerns. AB - PURPOSE: To identify specific health-related quality of life (HRQOL) concerns affecting children with esotropia as expressed by children or one of their parents (proxy) and concerns affecting the parents themselves. METHODS: Sixty children with esotropia (0-17 years of age) and 1 parent for each child were prospectively enrolled. Individual semistructured interviews were conducted with children aged 5-17 years (n = 40) and 1 parent each for child ages 0-17 years. Transcripts of recorded interviews were evaluated using NVivo software. Specific concerns were identified from both child and parent interviews and coded. From these specific codes, broad themes were identified. Frequency of each theme was calculated, along with the frequency of specific codes within each theme. RESULTS: Regarding the child's experience 6 broad themes were identified: visual function (mentioned by 32 of 40 children (80%) and by 50 of 60 parents (proxy assessment of child, 83%), treatment (78% and 85%), emotions (65% and 67%), social (58% and 68%), physical (58% and 32%), and worry (45% and 7%). Regarding the parents' own experience, 5 broad themes were identified: treatment (59 of 60 parents, 98%), worry (97%), emotions (82%), compensation for condition (80%), and affects family (23%). CONCLUSIONS: A wide range of concerns were identified from interviews of children with esotropia and their parents. Concerns reflect the impact of esotropia in physical, emotional, and social domains, and specific concerns will be used for the development of questionnaires to quantify the effects of esotropia on children's and parents' quality of life. PMID- 27381530 TI - Mass gatherings and mass gatherings health. AB - [No Abstract Available]. PMID- 27381529 TI - Results of a primary care-based quality improvement project to optimize chart based vision screening for preschool age children. AB - PURPOSE: To design chart-based vision screening for preschool-aged children. METHODS: Our program consisted of educational sessions for providers as well as hands-on training for practice staff. We evaluated the intervention through pre- and post-intervention review of medical records. RESULTS: Completion of full vision screening (distance visual acuity in each eye plus stereovision beginning at 3 years of age, as recommended at the time of the project) at well-child visits improved for 5-year-olds (45.0% to 58.2%; risk difference +13.2% [95% CI, 1.7-24.7]) and 4-year-olds (39.3% to 51.4%; risk difference +12.0% [95% CI, 0.7 23.4]) but declined somewhat among 3-year-olds (23.1% to 14.3%; risk difference, 8.8% [95% CI, -17.7 to 0.0]). Risk factors for not being fully screened included being 3 years old (risk ratio of 4.1 compared to 5-year-olds) and being a patient of a small practice (risk ratio of 1.9 compared to large practices). CONCLUSIONS: This quality improvement project showed that screening for visual acuity and stereovision among preschool-aged children using chart-based techniques is difficult to accomplish and unlikely to be consistently successful, especially among 3-year-olds. PMID- 27381531 TI - Optimum level of inferior mesenteric artery ligation for the left-sided colorectal cancer. Systematic review for high and low ligation continuum. AB - OBJECTIVES: To compares the effectiveness and impact of high inferior mesenteric artery (IMA) versus low IMA ligation on 5-year survival, lymph node yield rates, and peri-operative morbidity and mortality. METHODS: The databases of Educational Resources Information Centre (ERIC), the Web of Science, EBSCO and MEDLINE were searched using MeSH terms 'colorectal cancer', 'inferior mesenteric artery', 'high ligation', 'low ligation', 'mesenteric lymph nodes', 'prognosis', and 'survival'. Only clinical studies were selected and review articles and meta analysis were excluded. In cases of duplicate cohorts, only the latest article was included. Irrelevant articles and the articles on both right and left sided CRC were excluded. The finally selected studies were analysed for the defined end point outcomes. RESULTS: The published data has shown that high IMA ligation improves the yield of harvested lymph node that allows accurate tumor staging and a more reliable estimation of prognosis. High ligation was not found to be positively correlated with increased anastomotic leakage or impaired genito urinary function. However, high ligation demands advanced surgical expertise and longer operating time. There was no significant difference in 5-year survival rates for both techniques. Some studies have reported fatal complications of high ligation such as proximal bowel necrosis. CONCLUSION: Although there is no consensus, this research signals the routine use of high ligation for left-sided CRC. However, the published fatal complications following high ligation and no significant difference in 5-year survival rates demand more studies to establishing a unified protocol. PMID- 27381532 TI - Sonic hedgehog, TBX18, and TSHZ3 proteins involved in pyeloureteral motility development are overexpressed in ureteropelvic junction obstruction. An immunohistochemical, histopathological, and clinical comparative study. AB - OBJECTIVES: To compare pathological samples obtained from cases that underwent surgery for ureteropelvic junction (UPJ) obstruction with samples obtained during autopsies of subjects. METHODS: Retrospectively, 42 patients who had undergone surgery due to UPJ obstruction (group 1) were included in the study. Histopathological and immunohistochemical features for sonic hedgehog (SHH), TBX18, and TSHZ3 of UPJ were evaluated and findings were compared with 20 autopsy cases (group 2). RESULTS: In group 1, the scores were statistically significantly higher in terms of cytoplasmic SHH, nuclear TBX18, cytoplasmic and nuclear TSHZ3 staining. Statistically, no correlation was found between age and the staining scores belonging to these 3 antibodies in group 1 and group 2. Intense inflammation was found to be related with nuclear staining for TBX18. CONCLUSION: Gene product expressions of SHH, TBX18 and TSHZ3 are statistically higher in patients with UPJ obstruction, when compared with control group. The explanation may be the reactivation of the processes, which had shown their effects in the embryological period, due to the chronic inflammation and long term micro-trauma created by the disease. PMID- 27381533 TI - Differential diagnosis between pancreatic neuroendocrine and solid pseudopapillary neoplasms on endoscopic ultrasound-guided fine-needle aspiration. An immunohistochemical study. AB - OBJECTIVES: To evaluate the role of applying a limited panel of immunohistochemical stains on the cellblock preparation from samples obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the aim of differentiating solid pseudopapillary neoplasms (SPNs) from neuroendocrine tumors (NETs). METHODS: We retrospectively retrieved all the EUS-FNAs of the pancreas that have a diagnosis of NET or SPN that were performed at 2 tertiary care hospitals in Riyadh, Kingdom of Saudi Arabia from May 2004 to December 2014. Diff Quik, Papanicolaou, and Immunohistochemistry stains on cellblock preparations were performed. RESULTS: Twenty cases were available (16 pancreatic neuroendocrine tumors (pNETs) and 4 SPNs). The pNETs were immunoreactive for synaptophysin, chromogranin A and CD56 while E-cadherin was diffusely to focally cytoplasmic positive. beta-catenin was negative or showed focal cytoplasmic immunoreactivity. In comparison, SPNs were positive for vimentin, CD10, CD-56, focally positive for progesterone receptors and synaptophysin, and revealed nuclear immunostaining for beta-catenin. They were negative for chromogranin A and E-cadherin. CONCLUSION: Based on EUS-FNA samples, nuclear immunoreactivity for beta-catenin with loss of membranous immunostaining for E-Cadherin can potentially facilitate differentiating SPNs from pNETs. PMID- 27381534 TI - Identification of Candida species and susceptibility testing with Sensititre YeastOne microdilution panel to 9 antifungal agents. AB - OBJECTIVES: To determine the species incidence and susceptibility pattern to 9 antifungal agents of yeasts isolated from various clinical specimens of colonized or infected patients treated in the coronary and surgical intensive care units (ICU). METHODS: A total of 421 ICU patients were treated at the Cardiology Institute, Istanbul University, Istanbul, Turkey between June 2013 and May 2014, and 44 Candida species were isolated from blood, urine, endotracheal aspiration fluid, sputum, and wounds of 16 ICU patients. Identification of Candida was performed using CHROMagar. Antifungal susceptibility was determined by a Sensititre YeastOne colorimetric microdilution panel. RESULTS: Candida albicans (C. albicans) was the most commonly observed microorganism 23 (54%); the other microorganisms isolated were Candida tropicalis 12 (27%), Candida glabrata 5 (11%), Candida parapsilosis 1 (2%), Candida lusitaniae 1 (2%), Candida sake 1 (2%), and Geotrichum capitatum 1 (2%). All isolates were susceptible to amphotericin B and 5-flucytosine. Geotrichum capitatum excepted, the other isolates were also susceptible to anidulafungin, micafungin, and caspofungin. Candida parapsilosis was found to be susceptible to all the studied antifungals. High MIC rates for azole group of antifungal drugs were found for C. albicans, C. tropicalis, and C. glabrata. The rate of colonisation was 3.8% (16/421). Only 0.7% (3/421) patients out of a total of 421 developed candidemia. CONCLUSION: We found that the yeast colonization and infection rates of patients in our ICUs are very low. Candida albicans is still the most common species. We detected a decreasing susceptibility to azole compounds. PMID- 27381535 TI - Analysis of airway resistance and hypoxemia in overlap syndrome. AB - OBJECTIVES: To characterize overlap syndrome, investigate its impact on airflow limitation and blood oxygen condition, and detect the risk factors that affect its airway resistance. METHODS: We reviewed retrospectively the clinical data of 158 patients with overlap syndrome (OS), chronic obstructive pulmonary disease (COPD), and obstructive sleep apnea (OSA), treated in the Critical Care Medicine Department of the People's Hospital of Liaocheng, Liaocheng, China from May 2014 to March 2015. The lowest and average oxyhemoglobin saturation were measured using polysomnography. The pulmonary functions were tested using the cardiopulmonary measuring instruments, and the viscous resistance at oscillation frequencies of 5, 10, 15, 20 Hz was measured using the impulse oscillation system for all the patients. RESULTS: The values of forced expiratory volume (FEV)1/FVC, FEV1% predicted, and the lowest SaO2 in the OS group were significantly lower than those in the OSA (p less than 0.01, p less than 0.01, p=0.01), or the COPD group (p=0.03, p=0.02, p=0.03, but the value of viscous resistance at 5 Hz was significantly higher than that in the 2 groups (p less than 0.01). Old age, body mass index, and smoking history were significantly correlated with the viscous resistance in OS patients, at an oscillation frequency of 5Hz (p=0.03, p=0.04). CONCLUSION: The OS patients present with higher viscous resistance and more severe oxygen deficit, when compared with OSA and COPD patients, and weight decrease and smoking cessation are necessary for these patients. PMID- 27381536 TI - Placenta previa. A 13 years experience at a tertiary care center in Western Saudi Arabia. AB - OBJECTIVES: To review cases of placenta previa in the last 13 years in a tertiary teaching hospital to identify risk factors for maternal morbidity. METHODS: A retrospective analysis of all cases of placenta previa managed at King Abdulaziz University Hospital (KAUH), Jeddah, Kingdom of Saudi Arabia from January 2001 to December 2013. RESULTS: The total number of deliveries was 55,862 deliveries, and 11,412 (20.3%) delivered by cesarean section (C/S). The charts of 230 cases diagnosed with placenta previa was reviewed, and different variables were collected and analyzed. Diagnoses were achieved in 94% of them using ultrasound. The prevalence rate of placenta previa was 4.1 per 1000 births. Cesarean section was carried out as an emergency procedure in 130 (56.5%) women and as elective in 100 (43.5%) women. Of them, 26 patients were admitted to the intensive care unit (ICU) (11.3%), all of which received blood transfusion >6 units and 22 patients had a hysterectomy for uncontrollable bleeding. CONCLUSION: Placenta previa is one of the leading causes of maternal morbidity and mortality. Every hospital must have a protocol, or algorithm for the management of placenta previa. Risk factors for maternal morbidity included complete previa, history of previous C/S, emergency C/S at a gestational age of less than 36 weeks, and estimated blood loss more than 2000 ml. PMID- 27381537 TI - The spectrum of congenital heart diseases in down syndrome. A retrospective study from Northwest Saudi Arabia. AB - OBJECTIVES: To to define the frequency and patterns of congenital heart disease (CHD) among children with Down syndrome (DS) in Northwest Saudi Arabia. METHODS: We included children with confirmed DS referred to the regional pediatric cardiology unit in Madinah Maternity and Children Hospital between January 2008 and December 2013. Children were identified from the unit's data-base and the charts were reviewed retrospectively. We excluded term and preterm children with patent ducts arteriosus (PDA) and persistent foramen oval spontaneously resolved during the first 4 weeks of life. RESULTS: A total of 302 children with DS were identified (50.3% male). Of these, 177 (58.6%) had CHD. Atrioventricular septal defect (AVSD) was the most frequent lesion identified in 72/177 (40.7%) followed by mixed left to right shunt defects (14.7%) and secundum atrial septal defect (ASD) (11.8%). Ventricular septal defect was detected in 10.7% and 8.5% had PDA beyond the neonatal period. There was no gender difference in the frequency of CHD (p=0.9) and the presence of CHD was not related to the genetic cause of DS (p=0.9). CONCLUSION: The frequency of CHD in our DS cohort is comparable with Europe, Asia ,and other KSA regions. However its pattern appears to be different from some areas in KSA. PMID- 27381538 TI - Illicit substance use among persons admitted to probation polyclinic of a regional mental hospital in the Eastern Anatolia, Turkey. AB - OBJECTIVES: To investigate the illicit substance use trends by gender and year in Eastern Turkey, Elazig. METHODS: This is a retrospective study designed to assess the drug use prevalence in persons who admitted to the Probation Policlinic of Elazig Mental Health Hospital between January 2011 and December 2014 in Eastern Turkey, Elazig. Laboratory screening tests for drugs were studied using the cloned enzyme donor immunoassay technique in urine. RESULTS: The study consisted of 10267 males (95.3%) and 510 females (4.7%), with a mean age of 30.42+/-10.83 years. Overall prevalence was 32.1% for cannabis, 3.8% for opiate, 0.35% for cocaine and 1.2% for polydrug usage. The prevalence of cannabis was significantly higher in males (32.7%, p=0.000). The prevalence of cannabis use was the lowest in the age group of 50-59 while it was significantly higher in the age groups of 20-29 and 30-39 (p=0.000). The prevalence of opiate use showed a significant difference among the years (p=0.000).There was a significant difference in the prevalence of cocaine use among the years (p=0.02). The prevalence of polysubstance use showed a significant difference among years (p=0.000). CONCLUSION: Cannabis was the most common illicit drug in the east of the Turkey. Further studies are required for comparing the results of various regions of the country and developing early interventions and treatment facilities. PMID- 27381539 TI - Relationship between psychological distress and resilience in rescue workers. AB - OBJECTIVES: To assess the relationship between psychological distress and resilience in rescue workers. Following hypothesis was formulated; there would be negative correlation between psychological distress and resilience in rescue workers. METHOD: A correlational study was conducted from June-August 2015 in Rahim Yar Khan, Punjab, Pakistan. The sample of the present study consisted of 100 rescue workers. The age of the participants ranged from 23 to 40 year old with the mean age of 27.4+/-3.9 years. Demographic information form, Kessler psychological distress scale and adult resilience measure were administered on the participants to assess the level of psychological distress and resilience. RESULTS: Pearson product moment coefficient of correlation was applied to analyze the relationship of psychological distress and resilience. Analysis of the result indicated that there is negative relationship between psychological distress and resilience (r= -0.203, p less than 0.01) in rescue workers. Further, contextual factors (r= -0.292, p less than 0.05) and its subcomponents including spiritual beliefs (r= -0.239, p less than 0.05) and cultural resources (r= -0.287, p less than 0.01) were also found to be inversely correlated with psychological distress. CONCLUSION: The research evidenced that rescue workers were experiencing psychological distress Resilience factors should be considered while designing trainings to preserve mental health and to enhance the psychological well-being of rescue workers. PMID- 27381540 TI - Epidemiology and clinical consequences of occupational exposure to blood and other body fluids in a university hospital in Saudi Arabia. AB - OBJECTIVES: To describe the epidemiological characteristics, clinical impact, and adequacy of post-exposure management of occupational exposure to blood and body fluids (BBFs). METHODS: Retrospective chart review of individuals reporting exposure to BBFs from 2007 to 2013 at King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia. RESULTS: The total number of exposures reported was 326 exposures, of which 302 (92.6%) exposures were percutaneous, 21 (6.5%), mucocutaneous, and 3 (0.9%), bites. Nursing staff/students had the highest rate of exposure (149, or 45.6%), followed by physicians (57, or 17.5%). Surgeons were found to have a significantly higher risk for sharp injuries compared with other physicians (26.3%, or 15 exposures, p less than 0.005). Most (216, or 72.5%) percutaneous injuries were caused by hollow-bore needles. Majority of exposures (124, or 42.6%) occurred after using the needle/sharp item and before disposal. Two-thirds (219, or 67%) of exposed individuals were immune to hepatitis B at the time of exposure. With appropriate post-exposure management, none of exposed individuals seroconverted to HIV, hepatitis B or C virus infections. CONCLUSION: Occupational exposure to BBFs remains a concern among healthcare workers. Educational programs targeting high-risk groups entailing reinforcement of prevention and adherence to post-exposure management guidelines are needed. PMID- 27381541 TI - Attitudes of medical students toward communication skills learning in Western Saudi Arabia. AB - OBJECTIVES: To explore medical students' attitudes towards communication skills learning in Western Saudi Arabia and to examine impact of socio-demographic variables on the attitudes towards learning these skills. METHODS: In this cross-sectional study, sample of medical students were recruited from Taif University, Taif, Kingdom of Saudi Arabia during the second semester (January-May 2014). Participants were all year 2 (197 students) and year 5 (151 students). The study utilize the Communication Skills Attitude Scale (CSAS) to measure students' attitudes toward communication skills learning. The response rate was 93.9%. RESULTS: The study showed that Taif medical students hold highly positive attitudes towards learning communication skills. Positive attitude score (PAS) was significantly higher in level 5 students, older age group. CONCLUSION: Significant positive attitude toward learning communication skills clearly observed in target group. Students with more positive attitudes towards communication skills learning tended to be higher level and older age. PMID- 27381542 TI - Congenital lobar emphysema. A rare cause of hypertension. AB - Congenital lobar emphysema is a rare disease, which is characterized by pulmoner hyperinflation. Depending on the degree of bronchial obstruction, the clinical presentation may be variable. We report a rare case with congenital lobar emphysema in a 38-days-old male infant who presented with severe respiratory distress and hypertension. Air trapping in the left upper lung and significant mediastinal shift to the right were observed on the chest x-ray. Emphysematous changes were detected on the thorax computed tomography and considered as congenital lobar emphysema. The upper left lobectomy was successfully performed by pediatric surgeons. On postoperative follow up, no sign of respiratory distress occured and the patient was normotensive. In this report, a case with congenital lobar emphysema, which is a rare cause of respiratory distress and hypertension is discussed. PMID- 27381543 TI - Pediatric aneurysmal bone cyst in the ischial region. AB - Aneurysmal bone cyst (ABC) is an expanding osteolytic lesion. ABC represents 1% of all primary benign bone tumors, whereby 4-12% occur in the pelvis. The etiology of this disease remains vague. Aneurysmal bone cyst can exist either as primary bone lesion (70%) or as secondary lesion arising from another bone disorder (30%). Moreover, pelvic ABCs are characterized by their large size and high vascularity. We present a rare pediatric case with ABC involving the ischial region. A 5-year-old girl presented with left pelvic pain and limping for the past 6 months. Initial imaging showed an expansile lesion in the left ischium, and computed tomography guided biopsy showed giant cells in histopathology study with no evidence of metastasis. The patient underwent intraoperative frozen section followed by extensive intra-lesional bone excision. Bone curettage was pursued along with bone grafting. The case was successfully managed without postoperative complications after the 6-month follow-up period. PMID- 27381544 TI - Appraisal of the communication skills of residents in the Family Medicine Program in Central Saudi Arabia. AB - OBJECTIVES: To assess patients' perceptions of the communication skills of family medicine residents. METHODS: This is a cross-sectional study. Data were collected from patients, seeing 23 residents from 4 family medicine residency programs in Riyadh, Kingdom of Saudi Arabia namely, King Khalid University Hospital, Riyadh Military Hospital, Security Forces Hospital, and King Abdul-Aziz Medical City. The translated version of the Communication Assessment Tool (CAT) was used. Data were collected during January and February 2013. RESULTS: A total of 350 patients completed the CAT, with an 87.5% response rate. Patients rated each resident differently, but the mean percentage of items, which residents rated as excellent was 71%. In general, male residents were rated higher 72.8 +/- 27.2 than female residents 67.8 +/- 32.2 with a significant difference; (p less than .005). Also, significant differences were found based on the gender of the residents, when each item of the CAT was compared. Comparing training centers, there were no significant differences found in the overall percentage of items rated as excellent or among items of the CAT. CONCLUSION: The study identified areas of strength and weaknesses that need to be addressed to improve communication skills of physicians. PMID- 27381545 TI - Outpatient admissions and hospital costs of Syrian refugees in a Turkish university hospital. AB - OBJECTIVES: To examine the most frequent admitted polyclinics, diagnoses, and the costs of Syrian refugee patient in a Turkish university hospital in the metropolitan city of Istanbul, Western part of Turkey. METHODS: Research methodology consist of analyzing outpatient admissions to the Hospital Polyclinics of Faculty of Medicine, Istanbul University, Cerrahpasa, Istanbul, Turkey from January-June 2014. We carried out diagnosis groups as classified in the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification, and analyzed the hospital cost of first admission through records based in the hospital information system. RESULTS: Median age of 251 Syrian refugee patients is 19 years, inter quartile rate 7-34 years. Patients aged 65 and older compared with those until 18 years and 19 to 64 years aged groups have made statistically significant (p less than 0.001) less hospital admissions. The Most frequented clinic was the emergency clinic. On June there have been significantly (p less than 0.001) more admissions compared with other months. The most common diagnoses were diseases of the respiratory system. The costs of per admission was estimated nearly 48 US Dollar/per patient and the total amount of hospital admissions was 12,031.93 US Dollar. CONCLUSION: On the specified dates, the clinics were mostly frequented from Syrian refugees until 18 years group. The most common presenting symptoms are respiratory diseases and most frequented clinic is emergency. PMID- 27381546 TI - Transcutaneous bilirubin measurement in healthy Saudi term newborns. AB - [No Abstract Available]. PMID- 27381547 TI - The effect of different types of abdominal binders on intra-abdominal pressure. AB - [No Abstract Available]. PMID- 27381548 TI - Prevalence of irritable bowel syndrome among Qassim school teachers, and its impact on their performance and life duties. AB - OBJECTIVES: To determine the prevalence of irritable bowel syndrome (IBS) among school teachers in Qassim region, Kingdom of Saudi Arabia (KSA) and it's impact on their performance -as teachers- and on life duties. METHODS: A cross sectional study was held in Qassim region, KSA between 2012 and 2013. The study was conducted among 300 school teachers selected by multistage stratified random sample method in 2013. The sample size was calculated according to the formula: n = (Z2 * (p) * (q))/c2. A confidential, anonymous, and a self-administered questionnaire was used to collect personal and sociodemographic data, teacher performance oriented questions were included. Rome III Criteria were used. Teachers with red flag symptoms were excluded. RESULTS: The prevalence of IBS symptoms among teachers in Qassim region of KSA is 40.7% with no significant gender predilection. The IBS symptoms significantly affect the work performance of the teachers (61.6%) with high absenteeism rate (46.6%), especially among 51 60 years and 21-30 years, age groups (p less than 0.05 in chi-square test). Significant proportion (45.3%) of IBS criteria +ve teachers find IBS symptoms to be hindrance in their life duties. CONCLUSION: Prevalence of IBS in Qassim school teachers is becoming an important issue with 40.7% of teachers reporting symptoms suggestive of IBS in a random sample. Majority of teachers are having frequent performance problems - as teachers - and in usual life duties associated with their IBS Symptoms. Significantly, IBS criteria +ve teachers are more likely to have discipline problems compared with healthy teachers. We recommend a health care program to tackle the problem among the teachers, to improve their performance and reduce working hours loss. Also, follow up studies need to be conducted to assess the health care of IBS patients in local public health care centers. PMID- 27381550 TI - Long-standing Scaly Erythematous Tumor on the Lower Leg. PMID- 27381549 TI - Prognostic Impact of the Signet Ring Cell Type in Node-Negative Gastric Cancer. AB - Little is known regarding the prognostic impact of the signet ring cell (SRC) histotype on negative lymph nodes (LNs) in gastric cancer (GC). In this study, we aimed to investigate the differences between SRC and non-SRC GC patients without LN metastasis. The medical records of patients with GC who underwent gastrectomy at Sun Yat-Sen University Cancer Centre from 1996 to 2012 were reviewed to analyse the clinicopathologic characteristics associated with survival. A total of 480 cases of GC patients without LN metastasis were identified, which included 90 SRC GC patients and 390 non-SRC GC patients. Between the two groups, there were a host of significant differences in the American Joint Committee on Cancer, 7th edition (AJCC) stage. We found that SRC histology was correlated with a poor prognosis in terms of recurrence in node-negative GC patients and that SRC histologic analysis combined with AJCC staging maybe an effectual method for prediction of the recurrence rate. Additionally, we found that SRC GC presents a more dismal overall prognosis in patients with perineural or vascular invasion. PMID- 27381551 TI - Lithium Halomethylcarbenoids: Preparation and Use in the Homologation of Carbon Electrophiles. AB - alpha-Halomethyllithium carbenoids are useful homologating reagents which - reacting under proper reaction conditions as carbanions - enable the installation via nucleophilic addition of a reactive halomethyl fragment onto a preformed carbon-heteroatom bond. The pronounced thermolability represented - since seminal studies by Kobrich - the Achilles' heel of these reagents: the use of Barbier type methodologies (i.e., the electrophile should be present in the reaction mixture prior to the formation of the carbenoid) was pivotal in order to suppress decomposition through alpha-elimination processes. Nowadays, the use of low temperatures (-78 degrees C) guarantees reliable procedures and, significantly, the employment of microreactor technologies allows external trapping to be performed even at higher temperatures as reported by Luisi. We will discuss the alpha-halomethyllithium-mediated homologations of a series of carbon electrophiles such as carbonyl compounds, imines, esters, Weinreb amides, and isocyanates. PMID- 27381552 TI - Nonlinear wave interactions between short pulses of different spatio-temporal extents. AB - We study the nonlinear wave interactions between short pulses of different spatio temporal extents. Unlike the well-understood mixing of quasi-monochromatic waves, this configuration is highly non-intuitive due to the complex coupling between the spatial and temporal degrees of freedom of the interacting pulses. We illustrate the process intuitively with transitions between different branches of the dispersion curves and interpret it in terms of spectral exchange between the interacting pulses. We verify our interpretation with an example whereby a spectrally-narrow pulse "inherits" the wide spectrum of a pump pulse centered at a different wavelength, using exact numerical simulations, as well as a simplified coupled mode analysis and an asymptotic analytical solution. The latter also provides a simple and intuitive quantitative interpretation. The complex wave mixing process studied here may enable flexible spatio-temporal shaping of short pulses and is the starting point of the study of more complicated systems. PMID- 27381553 TI - Effects on the osseointegration of titanium implants incorporating calcium magnesium: a resonance frequency and histomorphometric analysis in rabbit tibia. AB - OBJECTIVE: This study assessed the bone formation around titanium surface incorporating the calcium-magnesium (CaMg) deposited by blasted in rabbit tibia bone to determine whether this surface would further enhance bone healing compared with commercially available implant surface. MATERIAL AND METHODS: The deposition of CaMg on the titanium SLA surface were obtained by blasting formed the experimental group (EX group), while implants with traditional SLA surface were used as control group (CO group), in this study. Fifty cylindrical threaded implants with a length of 8 mm were used (P = 25 per group). Five implants of each group were used to surface characterization by scanning electron microscopy, energy dispersive spectrometry, and optical profilometry. Ten New Zealand white rabbits received 40 implants (n = 20 per group). Resonance frequency analysis was performed three times (0, 4, and 6 weeks). Histomorphometric analysis was performed 4 and 6 weeks after implantation. Statistical significance was set at P < 0.05. RESULTS: Blasted CaMg deposition on SLA implant surface displayed almost identical surface morphologies and R(a) values at the micron scale. In comparing the implant stability quotient at the three time points, highly significant statistic differences were found (P < 0.001). Histomorphological analysis showed higher degrees of bone organization in the samples of test implant surfaces at both implantation times. CONCLUSION: Within the limitations of this study, the results indicate that the deposition of CaMg on the SLA titanium surface may be effective in enhancing the osseointegration of moderately rough grit-blasted implants by increasing the degree of bone-implant contact. PMID- 27381554 TI - The alpha2C-adrenoceptor antagonist, ORM-10921, has antipsychotic-like effects in social isolation reared rats and bolsters the response to haloperidol. AB - Early studies suggest that selective alpha2C-adrenoceptor (AR)-antagonism has anti-psychotic-like and pro-cognitive properties. However, this has not been demonstrated in an animal model of schizophrenia with a neurodevelopmental construct. The beneficial effects of clozapine in refractory schizophrenia and associated cognitive deficits have, among others, been associated with its alpha2C-AR modulating activity. Altered brain-derived neurotrophic factor (BDNF) has been linked to schizophrenia and cognitive deficits. We investigated whether the alpha2C-AR antagonist, ORM-10921, could modulate sensorimotor gating and cognitive deficits, as well as alter striatal BDNF levels in the social isolation reared (SIR) model of schizophrenia, comparing its effects to clozapine and the typical antipsychotic, haloperidol, the latter being devoid of alpha2C-AR activity. Moreover, the ability of ORM-10921 to augment the effects of haloperidol on the above parameters was also investigated. Animals received subcutaneous injection of either ORM-10921 (0.01mg/kg), clozapine (5mg/kg), haloperidol (0.2mg/kg), haloperidol (0.2mg/kg)+ORM-10921 (0.01mg/kg) or vehicle once daily for 14days, followed by assessment of novel object recognition (NOR), prepulse inhibition (PPI) of startle response and striatal BDNF levels. SIR significantly attenuated NOR memory as well as PPI, and reduced striatal BDNF levels vs. social controls. Clozapine, ORM-10921 and haloperidol+ORM-10921, but not haloperidol alone, significantly improved SIR-associated deficits in PPI and NOR, with ORM-10921 also significantly improving PPI deficits vs. haloperidol treated SIR animals. Haloperidol+ORM-10921 significantly reversed reduced striatal BDNF levels in SIR rats. alpha2C-AR-antagonism improves deficits in cognition and sensorimotor gating in a neurodevelopmental animal model of schizophrenia and bolsters the effects of a typical antipsychotic, supporting a therapeutic role for alpha2C-AR-antagonism in schizophrenia. PMID- 27381555 TI - Genetic variants of MAOB affect serotonin level and specific behavioral attributes to increase autism spectrum disorder (ASD) susceptibility in males. AB - Serotonergic system participates in various developmental processes and modulation of behaviour. Autism Spectrum Disorder (ASD) is characterized by a range of behavioral symptoms scaling from mild to severe. Abnormal 5-HT synthesis and signalling, platelet hyperserotonemia and amelioration of repetitive behaviours by SSRI are some of the key findings, which reinforced the hypothesis that serotonergic genes might act as ASD susceptible genes. Therefore, genes encoding monoamine oxidases A/B (MAOA/MAOB) received special attention as these genes are located on the X-chromosome and the gene products are responsible for 5 HT degradation. In the present study, we conducted population-based association analysis of eight markers of MAOB with ASD in a study cohort of 203 cases and 236 controls form India and examined its effect on platelet 5-HT content and behaviour. Gender-specific changes were observed for the contrasting LD between pair of markers among cases and controls. Case-control analysis demonstrated over distribution of major C allele of rs2283728 and rs2283727 in male and female ASD cases respectively. Haplotypic distribution and interaction among markers showed more robust effect in male cases. Interestingly, male ASD cases displayed higher platelet 5-HT content in comparison to the respective controls. Quantitative trait analysis revealed significant correlation of genetic variants and haplotypes of MAOB markers, rs1799836 and rs6324 with increased platelet 5-HT level and CARS scores for specific behavioral symptoms respectively in males. This study suggests that MAOB increases ASD risk in males, possibly through its sex-specific regulatory effect on 5-HT metabolism and behavior. PMID- 27381556 TI - Clinical Relevance of Vertebral Fractures in Men. PMID- 27381557 TI - Proteome-wide analysis of lysine acetylation in the plant pathogen Botrytis cinerea. AB - Lysine acetylation is a dynamic and reversible post-translational modification that plays an important role in diverse cellular processes. Botrytis cinerea is the most thoroughly studied necrotrophic species due to its broad host range and huge economic impact. However, to date, little is known about the functions of lysine acetylation in this plant pathogen. In this study, we determined the lysine acetylome of B. cinerea through the combination of affinity enrichment and high-resolution LC-MS/MS analysis. Overall, 1582 lysine acetylation sites in 954 proteins were identified. Bioinformatics analysis shows that the acetylated proteins are involved in diverse biological functions and show multiple cellular localizations. Several particular amino acids preferred near acetylation sites, including K(ac)Y, K(ac)H, K(ac)***R, K(ac)F, FK(ac) and K(ac)***K, were identified in this organism. Protein interaction network analysis demonstrates that a variety of interactions are modulated by protein acetylation. Interestingly, 6 proteins involved in virulence of B. cinerea, including 3 key components of the high-osmolarity glycerol pathway, were found to be acetylated, suggesting that lysine acetylation plays regulatory roles in pathogenesis. These data provides the first comprehensive view of the acetylome of B. cinerea and serves as a rich resource for functional analysis of lysine acetylation in this plant pathogen. PMID- 27381559 TI - Design and synthesis of ternary Co3O4/carbon coated TiO2 hybrid nanocomposites for asymmetric supercapacitors. AB - Recently, attention has been focused on the synthesis and application of nanocomposites for supercapacitors, which can have superior electrochemical performance than single structured materials. Here, we report a carbon-coated TiO2/Co3O4 ternary hybrid nanocomposite (TiO2@C/Co) electrode for supercapacitors. A carbon layer was directly introduced onto the TiO2 surface via thermal vapor deposition. The carbon layer provides anchoring sites for the deposition of Co3O4, which was introduced onto the carbon-coated TiO2 surface by hydrazine and the thermal oxidation method. The TiO2@C/Co electrode exhibits much higher charge storage capacity relative to pristine TiO2, carbon-coated TiO2, and pristine Co3O4, showing a specific capacitance of 392.4 F g(-1) at a scan rate of 5 mV s(-1) with 76.2% rate performance from 5 to 500 mV s(-1) in 1 M KOH aqueous solution electrolyte. This outstanding electrochemical performance can be attributed to the high conductivity and high pseudo-capacitive contributions of the nanoscale particles. To evaluate the capacitive performance of a supercapacitor device employing the TiO2@C/Co electrode, we have successfully assembled TiO2@C/Co//activated carbon (AC) asymmetric supercapacitors. The optimized TiO2@C/Co//AC supercapacitor could be cycled reversibly in the voltage range from 0 to 1.5 V, and it exhibits a specific capacitance of 59.35 F g(-1) at a scan rate of 5 mV s(-1) with a specific capacitance loss of 15.4% after 5000 charge-discharge cycles. These encouraging results show great potential in terms of developing high-capacitive energy storage devices for practical applications. PMID- 27381558 TI - Modulatory role of leptin on ovarian functions in water buffalo (Bubalus bubalis). AB - The aim of the present study was to demonstrate the modulatory role of leptin on bubaline granulosa cells (GCs) and luteal cells (LCs) functions using an in vitro cell culture system and to establish a cross talk between leptin and insulin-like growth factor-1 (IGF-1). GCs were collected from group IV follicles (>13 mm size) and LCs from mid-luteal phase corpus luteum and were grown in serum-containing media supplemented with leptin at three different dose rates (0.1, 1, and 10 ng/mL) and time durations (24, 48, and 72 hours). We evaluated the production and secretion of estradiol (E2) and progesterone (P4) using RIA and the mRNA expression of steroidogenic acute regulatory protein (STARD1), cytochrome P450 cholesterol side-chain cleavage (CYP11A1), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), cytochrome P450 aromatase (CYP19A1), sterol regulatory element binding protein 1 (SREBP1), steroidogenic factor-1 (SF1), anti-apoptotic gene PCNA, pro-apoptotic gene caspase 3 and endothelial cell marker, Von Willebrand factor (vWF), using quantitative real-time polymerase chain reaction. The results depicted a direct inhibitory action of leptin on GCs steroidogenesis in a time dependent manner (P < 0.05), whereas in the presence of IGF-1 the inhibitory effect was reverted. Furthermore, leptin augmented both cellular proliferation (PCNA) and apoptosis (caspase 3). On the other hand, in LCs, leptin alone showed an apparent stimulatory effect on steroidogenesis (P < 0.05); however, in the presence of IGF-1, an antagonistic effect was witnessed. Moreover, leptin had an inhibitory effect on apoptosis while promoted cellular proliferation and angiogenesis. These findings were further strengthened by immunocytochemistry. To conclude, these observations for the first time reported that in buffaloes leptin has a direct dose-, time-, and tissue-dependent effect on ovarian steroidogenesis, angiogenesis, and cytoprotection, and furthermore, it can regulate the effect of systemic factors like IGF-1. Hence, this in vitro study provides an insight into the putative roles of leptin alone and its interactions in vivo. PMID- 27381560 TI - Monitoring of Liver Function Tests after Roux-en-Y Gastric Bypass: An Examination of Evidence Base. AB - There is no consensus on the monitoring of liver function tests after Roux-en-Y gastric bypass (RYGB). Since the main objective of such monitoring would be to diagnose early those who will eventually develop liver failure after RYGB, we performed a systematic review on this topic. An extensive search of literature revealed only 10 such cases in 6 published articles. It would hence appear that liver failure is a rare problem after RYGB. Routine lifelong monitoring of liver function tests is therefore unnecessary for otherwise asymptomatic individuals. Such monitoring should hence be reserved for high-risk groups, such as patients with liver cirrhosis, those undergoing extended limb/distal RYGB, patients with new illnesses, those abusing alcohol, those on hepatotoxic drugs and those presenting with a surgical complication. PMID- 27381561 TI - Emerging concepts for patients with treatment-resistant hypertension. AB - Treatment-resistant hypertension (TRH) is defined as elevated blood pressure despite treatment with three properly dosed antihypertensive drugs, and is associated with adverse cardiovascular and renal outcomes and increased mortality. Treatment of patients with TRH focuses on maximizing the doses of antihypertensive drugs and adding drugs with complementary mechanisms of action, including a combination of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, calcium channel blockers, and thiazide-like diuretics. Randomized clinical trials have demonstrated the efficacy of the mineralocorticoid receptor antagonist spironolactone as a fourth-line therapy for patients with TRH. Other pharmacologic considerations include adding alpha blockers, combined alpha-beta-blockers, centrally acting alpha-agonists, or direct vasodilators. However, a small, but important subset of patients remain hypertensive despite combination regimens with multiple antihypertensive drugs, underscoring the need for novel blood pressure-lowering therapies. Over recent years, alternative approaches for treating TRH have emerged, including agonists of natriuretic peptides, endothelin-receptor antagonists, and additional vasoactive drugs. Lastly, device-based interventions, such as renal denervation or carotid baroreflex activation, may supplement drug therapy for these patients. This review summarizes current knowledge on the management of TRH, with focus on novel therapeutic strategies designed to achieve optimal blood pressure control. PMID- 27381562 TI - 3D patterned stem cell differentiation using thermo-responsive methylcellulose hydrogel molds. AB - Tissue-specific patterned stem cell differentiation serves as the basis for the development, remodeling, and regeneration of the multicellular structure of the native tissues. We herein proposed a cytocompatible 3D casting process to recapitulate this patterned stem cell differentiation for reconstructing multicellular tissues in vitro. We first reconstituted the 2D culture conditions for stem cell fate control within 3D hydrogel by incorporating the sets of the diffusible signal molecules delivered through drug-releasing microparticles. Then, utilizing thermo-responsivity of methylcellulose (MC), we developed a cytocompatible casting process to mold these hydrogels into specific 3D configurations, generating the targeted spatial gradients of diffusible signal molecules. The liquid phase of the MC solution was viscous enough to adopt the shapes of 3D impression patterns, while the gelated MC served as a reliable mold for patterning the hydrogel prepolymers. When these patterned hydrogels were integrated together, the stem cells in each hydrogel distinctly differentiated toward individually defined fates, resulting in the formation of the multicellular tissue structure bearing the very structural integrity and characteristics as seen in vascularized bones and osteochondral tissues. PMID- 27381563 TI - Kidney anomalies diagnosed by prenatal ultrasound screening and associated non urinary malformations: a nationwide prevalence study. AB - OBJECTIVES: To estimate the prevalence of kidney anomalies at second trimester ultrasound screening, and furthermore, to investigate pregnancy outcomes and the pattern of additional malformations. METHODS: We previously identified all women attending second-trimester ultrasound scans in Denmark between 1 January 2007 and 31 December 2012. Using the Astraia databases and the Danish National Patient Registry, we identified all fetuses with kidney anomalies diagnosed prenatally in these women. In addition to the prevalence of fetuses with kidney anomalies, we estimated the live birth prevalence ratio of non-urinary malformations, comparing the prevalences in infants with and without prenatally diagnosed kidney anomalies. RESULTS: The prevalence of fetuses with kidney anomalies at second trimester scans was 11.4 per 10 000 fetuses. Among the 412 fetuses identified, 127 pregnancies were terminated. For live born children the prevalence of additional non-urinary malformations was four times higher (95% CI: 3-5) compared with the prevalence among children without prenatal kidney anomalies. Digestive system anomalies were particularly prevalent. CONCLUSION: These population-based data provide additional insight into the course of pregnancy and birth outcomes following prenatal diagnoses of kidney anomalies. (c) 2016 John Wiley & Sons, Ltd. PMID- 27381564 TI - Variability of Pasteurella multocida isolated from Icelandic sheep and detection of the toxA gene. AB - Pasteurella multocida can be part of the upper respiratory flora of animals, but under conditions of stress or immunocompromisation, the bacteria can cause severe respiratory symptoms. In this study, we compared 10 P. multocida isolates from Icelandic sheep with respiratory symptoms and 19 isolates from apparently healthy abattoir sheep. We examined capsule type, genetic variability and the presence of the toxA gene in the two groups. Surprisingly, we found that all ovine P. multocida isolates examined in this study carried the toxA gene, which markedly differs from what has been published from other studies. Interestingly, all isolates from abattoir animals were capsule type D, whilst bacteria isolated from animals with clinical respiratory symptoms had capsule type A, D or F. Examination of seven housekeeping genes indicated that the clinical respiratory isolates were significantly more heterogeneous than the abattoir isolates (P<0.05, two-tailed Mann-Whitney U test). The results suggest that there may be at least two groups of P. multocida in sheep - a genetically homogeneous group that resides in the respiratory tract and a genetically heterogeneous group that is the predominant cause of disease. PMID- 27381565 TI - How and Where Older Persons Live. PMID- 27381566 TI - Streptomyces camponoticapitis sp. nov., an actinomycete isolated from the head of an ant (Camponotus japonicus Mayr). AB - A novel single-spore-producing actinomycete, designated strain 2H-TWYE14T, was isolated from the head of an ant (Camponotus japonicus Mayr) and characterized using a polyphasic approach. 16S rRNA gene sequence analysis showed that strain 2H-TWYE14T belongs to the genus Streptomyces, with highest sequence similarity to Streptomyces niveus NRRL 2466T (98.84 %). Analysis based on the gyrB gene also indicated that strain 2H-TWYE14T should be assigned to the genus Streptomyces. The chemotaxonomic properties of strain 2H-TWYE14T were consistent with those of members of the genus Streptomyces. The cell wall contained ll-diaminopimelic acid. The predominant menaquinones were MK-9(H6), MK-9(H8) and MK-9(H4). The phospholipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The major fatty acids were iso-C16 : 0 and iso-C15 : 0. DNA-DNA hybridization experiments and phenotypic tests were carried out between strain 2H TWYE14T and its phylogenetically closely related strain S. niveus JCM 4251T, which further clarified their relatedness and demonstrated that 2H-TWYE14T could be distinguished from S. niveus. Therefore, it is concluded that strain 2H TWYE14T can be classified as representing a novel species of the genus Streptomyces, for which the name Streptomyces camponoticapitis sp. nov. is proposed. The type strain is 2H-TWYE14T (=DSM 100523T=CGMCC 4.7275T). PMID- 27381567 TI - Youth mental ill health and secondary school completion in Australia: time to act. AB - AIM: This paper reviews the evidence of youth mental ill health and its impact on secondary school educational attainment. METHODS: This narrative review presents the current research related to the mental ill health of young people in urban and rural Australia, their educational attainment and the effectiveness of mental health strategies implemented in secondary schools. RESULTS: The prevalence of mental ill health is high for Australian young people and the onset of depression, anxiety, substance-use disorders and first episode psychosis (FEP) commonly occurs when the individual is at school. The prevalence is reported to be higher for rural young people and barriers to treatment exist. Current evidence suggests that 40% of young people experiencing depression or anxiety disorders are not completing secondary school. Further evidence shows that over 50% of individuals who experience FEP do not finish secondary school. Current mental health promotion strategies employed in secondary schools have not been shown to reduce rates of depression or anxiety in adolescence nor identify prodromal or acute FEP. These strategies have not led to interventions that assist young people with mental ill health to finish school. CONCLUSIONS: Not completing secondary school can limit employment options, lead to severe levels of disadvantage and increased burden on welfare and healthcare systems. All young people, including those in rural areas, have the right to education and should not be disadvantaged in their educational aspirations because they have an emerging or current mental illness. PMID- 27381568 TI - Lynxacarus radovskyi mites in feral cats: a study of diagnostic methods, preferential body locations, co-infestations and prevalence. AB - BACKGROUND: Lynxacarus radovskyi (fur mites) are ectoparasites found on the hair shafts of cats living in tropical environments. Diagnosis is via microscopic examination of hairs. Various anatomical areas have been reported to harbour these mites. OBJECTIVES: To assess adhesive tape impressions and trichograms for detecting L. radovskyi and co-infestations; to determine host body predilection sites and affected gender; to determine prevalence of L. radovskyi in a feral cat population. ANIMALS: 121 feral cats in a trap, neuter and release programme. METHODS: After cats were premedicated for surgical sterilization, hairs from seven to nine body sites were removed from each cat using adhesive tape impression and trichogram techniques. Samples were examined at 10-100* magnification using compound or stereo microscopes. RESULTS: The prevalence of L. radovskyi was 71% (86 of 121) within the feral cat population. Tape impressions identified 75 cats; trichograms identified 56 cats. There were fewer false negative results with tape impressions. Caudal body sites were more likely to be positive, with the perianal area being the most commonly affected. Males and females were infested equally. Tape impressions identified more Cheyletiella blakei infestations and both methods identified some Felicola felis infestations. CONCLUSIONS AND CLINICAL IMPORTANCE: Tape impressions were easier to perform and identified more L. radovskyi positive cats and more co-infestations. Hairs from the perianal area and other caudal body sites are most likely to harbour L. radovskyi. Within this feral cat population, L. radovskyi was a common infestation. PMID- 27381570 TI - LC-HR-MS/MS standard urine screening approach: Pros and cons of automated on-line extraction by turbulent flow chromatography versus dilute-and-shoot and comparison with established urine precipitation. AB - Comprehensive urine screening for drugs and metabolites by LC-HR-MS/MS using Orbitrap technology has been described with precipitation as simple workup. In order to fasten, automate, and/or simplify the workup, on-line extraction by turbulent flow chromatography and a dilute-and-shoot approach were developed and compared. After chromatographic separation within 10min, the Q-Exactive mass spectrometer was run in full scan mode with positive/negative switching and subsequent data dependent acquisition mode. The workup approaches were validated concerning selectivity, recovery, matrix effects, process efficiency, and limits of identification and detection for typical drug representatives and metabolites. The total workup time for on-line extraction was 6min, for the dilution approach 3min. For comparison, the established urine precipitation and evaporation lasted 10min. The validation results were acceptable. The limits for on-line extraction were comparable with those described for precipitation, but lower than for dilution. Thanks to the high sensitivity of the LC-HR-MS/MS system, all three workup approaches were sufficient for comprehensive urine screening and allowed fast, reliable, and reproducible detection of cardiovascular drugs, drugs of abuse, and other CNS acting drugs after common doses. PMID- 27381569 TI - Biodegradation of the Pyrethroid Pesticide Esfenvalerate by Marine-Derived Fungi. AB - Esfenvalerate biodegradation by marine-derived fungi is reported here. Esfenvalerate (S,S-fenvalerate) and its main metabolites [3-phenoxybenzaldehyde (PBAld), 3-phenoxybenzoic acid (PBAc), 3-phenoxybenzyl alcohol (PBAlc), and 2-(4 chlorophenyl)-3-methylbutyric acid (CLAc)] were quantitatively analyzed by a validated method in triplicate experiments. All the strains (Penicillium raistrickii CBMAI 931, Aspergillus sydowii CBMAI 935, Cladosporium sp. CBMAI 1237, Microsphaeropsis sp. CBMAI 1675, Acremonium sp. CBMAI 1676, Westerdykella sp. CBMAI 1679, and Cladosporium sp. CBMAI 1678) were able to degrade esfenvalerate, however, with different efficiencies. Initially, 100 mg L(-1) esfenvalerate (Sumidan 150SC) was added to each culture in 3 % malt liquid medium. Residual esfenvalerate (64.8-95.2 mg L(-1)) and the concentrations of PBAc (0.5-7.4 mg L(-1)), ClAc (0.1-7.5 mg L(-1)), and PBAlc (0.2 mg L(-1)) were determined after 14 days. In experiments after 7, 14, 21, and 28 days of biodegradation with the three most efficient strains, increasing concentrations of the toxic compounds PBAc (2.7-16.6 mg L(-1), after 28 days) and CLAc (6.6-13.4 mg L(-1), after 28 days) were observed. A biodegradation pathway was proposed, based on HPLC-ToF results. The biodegradation pathway includes PBAld, PBAc, PBAlc, ClAc, 2-hydroxy-2-(3-phenoxyphenyl)acetonitrile, 3-(hydroxyphenoxy)benzoic acid, and methyl 3-phenoxy benzoate. Marine-derived fungi were able to biodegrade esfenvalerate in a commercial formulation and showed their potential for future bioremediation studies in contaminated soils and water bodies. PMID- 27381571 TI - PCI-GC-MS-MS approach for identification of non-amino organic acid and amino acid profiles. AB - Alkyl chloroformate have been wildly used for the fast derivatization of metabolites with amino and/or carboxyl groups, coupling of powerful separation and detection systems, such as GC-MS, which allows the comprehensive analysis of non-amino organic acids and amino acids. The reagents involving n-alkyl chloroformate and n-alcohol are generally employed for providing symmetric labeling terminal alkyl chain with the same length. Here, we developed an asymmetric labeling strategy and positive chemical ionization gas chromatography tandem mass spectrometry (PCI-GC-MS-MS) approach for determination of non-amino organic acids and amino acids, as well as the short chain fatty acids. Carboxylic and amino groups could be selectively labelled by propyl and ethyl groups, respectively. The specific neutral loss of C3H8O (60Da), C3H5O2 (74Da) and C4H8O2 (88Da) were useful in the selective identification for qualitative analysis of organic acids and amino acid derivatives. PCI-GC-MS-MS using multiple reaction monitoring (MRM) was applied for semi-quantification of typical non-amino organic acids and amino acids. This method exhibited a wide range of linear range, good regression coefficient (R2) and repeatability. The relative standard deviation (RSD) of targeted metabolites showed excellent intra- and inter-day precision (<5%). Our method provided a qualitative and semi-quantitative PCI-GC-MS-MS, coupled with alkyl chloroformate derivatization. PMID- 27381572 TI - Additive effect of age-related macular degeneration and glaucoma on quality of life. PMID- 27381573 TI - Image artifacts in optical coherence tomography angiography. PMID- 27381575 TI - Continuing Professional Development. PMID- 27381574 TI - Assessment of corneal curvature using verion optical imaging system: a comparative study. AB - BACKGROUND: Keratometry is a critical determinant of the postoperative refractive outcome. This study evaluates the comparability of keratometry measurements obtained using the Verion Optical Imaging System with devices used in current clinical practice. Further, it determines the interobserver reliability of the Verion Optical Imaging System. DESIGN: Retrospective analysis of patient data PARTICIPANTS: Keratometric data was obtained from 100 patients presenting for pre operative evaluation. Furthermore, repeatability and reproducibility were assessed using 15 healthy volunteers. METHODS: Corneal curvature values acquired by the Verion Optical Imaging System were compared with existing keratometry devices including autokeratometry, partial coherence interferometry (IOLMaster) and Scheimpflug corneal topography (Pentacam). MAIN OUTCOME MEASURES: Direct comparison of corneal power, cylinder, axis of astigmatism and vector analysis were performed using correlation and Bland-Altman analyses. Reproducibility and reliability of the device were assessed using within-subject standard deviation and intraclass correlation coefficients for experienced and inexperienced technicians. RESULTS: There was no statistically significant difference between Verion values and those obtained by other methods in relation to mean keratometry, corneal astigmatism, steep meridian and vector analyses (P > 0.05). Bland-Altman plots showed narrow limits of agreement for keratometry and astigmatism and wider agreement for steep meridian. Intraoperator reliability for both experienced and inexperienced operators and interoperator reproducibility showed no statistically significant differences between values. CONCLUSION: Measurements show no significant difference from those obtained by the other devices. This suggests the Verion system is en par with instruments used in current clinical practice. The Verion Optical Imaging System produces repeatable data with no difference related to operator experience. PMID- 27381576 TI - Opinions of paediatricians who teach neonatal resuscitation about resuscitation practices on extremely preterm infants in the delivery room. AB - OBJECTIVE: To describe the opinions of paediatricians who teach resuscitation in Brazil regarding resuscitation practices in the delivery room (DR) of preterm infants with gestational ages of 23-26 weeks. METHODS: Cross-sectional study with an internationally validated electronic questionnaire (December 2011-September 2013) sent to the instructors of the Neonatal Resuscitation Program of the Brazilian Society of Paediatrics on parental counselling practices, medical limits for resuscitation of extremely preterm infants and medical considerations for decision-making in this group of infants. The analysis was descriptive. RESULTS: Among 685 instructors, 560 (82%) agreed to participate. Only 5%-13% reported having opportunity for antenatal counselling parents: if called, 22% reported discussing with the family about the possibility not to resuscitate in the DR; 63% about the possibility of death in the DR and 89% about the possibility of death in the neonatal unit. If the parents did not agree with the advice of the paediatrician, 30%-50% of the respondents would follow the procedures they advised regardless of the opinion of the parents. The higher the gestational age, the lower is the percentage of paediatricians who believed that parents should participate in decision-making. Only 9% participants reported the existence of written guidelines at their hospital on initiation of resuscitation in the DR at limits of viability, but 80% paediatricians reported using some criteria for limiting resuscitation in the DR. CONCLUSION: The picture obtained in this study of Brazilian paediatricians indicates that resuscitation of extremely preterm infants is permeated by ambivalence and contradictions. PMID- 27381577 TI - Garasic review, Guantanamo and other cases of enforced medical treatment. PMID- 27381578 TI - Morbidity of mansoni schistosomiasis in Pernambuco-Brazil: Analysis on the temporal evolution of deaths, hospital admissions and severe clinical forms (1999 2014). AB - BACKGROUND: Current scientific information reported that due to successive treatments of schistosomiasis cases in endemic areas of Brazil in the last 30 years, there has been a decrease in severe clinical form (hepatosplenic) and mortality from upper gastrointestinal bleeding due to this disease. Against this information, literature data show that the state of Pernambuco presents significant percentage of deaths and hospitalizations due to schistosomiasis, and occurrence of severe clinical forms as schistosomiasis myeloradiculopathy and persistence of localities with high parasite loads. This scenario justified this research which seeking to update the morbidity and mortality of schistosomiasis in Pernambuco. OBJECTIVE: To conduct a temporal analysis on the evolution of deaths, hospital admissions and severe forms of Manson's schistosomiasis over the last 16 years in Pernambuco, Brazil. METHODS: It was performed a gathering secondary data on schistosomiasis, from healthcare information systems and from the records of Hospital das Clinicas, Federal University of Pernambuco (HC-UFPE), covering the period from 1999 to 2014. RESULTS: From 1999 to 2013 were registred 2578 deaths due to schistosomiasis and between 2008 and 2014 were recorded 473 hospitalizations for this disease. Among 1999-2014 were identified 1943 cases of schistosomiasis treated at the Hospital das Clinicas of Pernambuco. Among these cases, 72.6% (n. 1411) of the individuals presented the hepatosplenic clinical form (HE), 60.8% (n. 858) were at the age group 30-59 years (adults) and 58% were female. Among the HE cases, 4.6% (n. 58) had ascites, 43.2% (n. 556) had upper gastrointestinal bleeding and 39.1% (n. 489) had collateral circulation. The pattern of fibrosis in the liver E/EC (advanced fibrosis) and F/FC (very advanced fibrosis) occurred in 65.5% (n. 793) of cases. Between 1999-2014 the evolution curve of severe clinical forms of schistosomiasis remained stable, showing a tendency to decline from 2012. CONCLUSION: When compared to other states of Brazil, Pernambuco shows high numbers of deaths and hospital admissions due to schistosomiasis. The actions of the Schistosomiasis Control Program (PCE) have been developed in a disintegrated, disjointed and discontinuous way, which may explain the magnitude of deaths, hospitalizations and severe forms of the disease in Pernambuco, showing a lack of control and the maintenance of severe frame morbidity of schistosomiasis in this state. PMID- 27381579 TI - Adapting the Bayley Scales of infant and toddler development in Ethiopia: evaluation of reliability and validity. AB - BACKGROUND: There is a need for valid and reliable observational measures of early child development in low-income and middle-income country settings. METHODS: The aims of the study were to adapt the Bayley Scales of Infant Development (Bayley III) for a rural Ethiopian setting and evaluate reliability and validity. The study was carried out between January 2008 and January 2009 in the Butajira demographic surveillance site, south central Ethiopia. The Bayley III was adapted to be socioculturally appropriate for a rural Ethiopian context. Nurses and high school graduates were trained in administration of the measure for 10 days. Inter-rater reliability was evaluated (n = 60). Content, construct and convergent validity was then examined on a population-based cohort of children at the ages of 30 (n = 440) and 42 months (n = 456). Mokken scale analysis was used to determine the scalability of items in unidimensional, hierarchical sub-scales. The mean score was compared by age of child and by stunting status (less than -2 z scores below the standard height-for-age). RESULTS: The intra-class correlations between raters were above 0.90 for all sub scales of the child development measure. Some scale items were not contextually relevant and showed poor scalability. However, the majority of items scaled onto the existing sub-scales of the international measure to form adequate-to-strong hierarchical scales with good internal consistency (Cronbach's alpha above 0.70 except for gross motor and expressive language sub-scales). Item-scale coefficients were good. The mean score of all sub-scales was significantly higher in the older group of children (33.02 higher total score; P < 0.001) and in the children who were stunted (total Bayley score 2.58 (95% confidence interval 0.07 to 5.10) points lower at 30 months and 3.87 (1.94 to 5.81) points lower at 42 months. CONCLUSIONS: An adapted version of an international, observational measure of child development was found to be reliable, valid and feasible in a rural Ethiopian setting. PMID- 27381582 TI - Antidiabetic potential of bioactive molecules coated chitosan nanoparticles in experimental rats. AB - The present study was carried out to examine the antidiabetic effects of chitosan nanoparticles (CNPs) loaded with (Stevia rebaudiana leaf extract-SRLE) bioactive molecules in a rat model of streptozotocin (STZ) induced diabetes mellitus. Successful crosslinking of the bioactive molecules to the chitosan nanoparticles was confirmed by Fourier Transform Infrared Spectroscopy (FTIR). The colloidal characteristics of the synthesized nanoparticles were revealed by X-ray Diffraction (XRD) analysis. Morphological analysis by Transmission Electron Microscopy (TEM) revealed that thebioactive molecule-loaded CNPs were well dispersed and spherical or polygonal in shape with an average size of<73.27nm than the z-average value (327nm) as measured by Dynamic Light Scattering (DLS). SRLE CNP-treated diabetic rats showed a significant reduction in their mean fasting blood glucose level compared with the diabetic control group. The serum levels of various enzymes viz., serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatases (ALP), lipid peroxidation, and antioxidant such as catalase (CAT), reduced glutathione (GSH), and superoxide dismutase (SOD) in the SRLE CNP-treated group were closer to normal levels than those in the diabetic control group. PMID- 27381580 TI - The stability of aluminium oxide monolayer and its interface with two-dimensional materials. AB - The miniaturization of future electronic devices requires the knowledge of interfacial properties between two-dimensional channel materials and high-kappa dielectrics in the limit of one atomic layer thickness. In this report, by combining particle-swarm optimization method with first-principles calculations, we present a detailed study of structural, electronic, mechanical, and dielectric properties of Al2O3 monolayer. We predict that planar Al2O3 monolayer is globally stable with a direct band gap of 5.99 eV and thermal stability up to 1100 K. The stability of this high-kappa oxide monolayer can be enhanced by substrates such as graphene, for which the interfacial interaction is found to be weak. The band offsets between the Al2O3 monolayer and graphene are large enough for electronic applications. Our results not only predict a stable high-kappa oxide monolayer, but also improve the understanding of interfacial properties between a high-kappa dielectric monolayer and two-dimensional material. PMID- 27381583 TI - Timesaving microwave assisted synthesis of insulin amyloid fibrils with enhanced nanofiber aspect ratio. AB - Insulin amyloid fibrils with enhanced aspect ratio, were prepared using a timesaving microwave assisted (MW) methodology, reducing the incubation time from 13 to 2h. The fibrillation process was followed indirectly by Thioflavin T Fluorescence and UV-vis analysis, by measuring the amount of beta-sheets formed and the insulin present in solution, respectively. TEM and AFM analysis revealed that the insulin fibrils obtained through the MW method, have very similar lengths but are much thinner than the ones obtained using the conventional method (CM). Additionally, it was verified that the nature of the peptides present in the final insulin fibrils was not affected by microwave irradiation. These morphological differences might reflect on noticeably enhanced mechanical and optical properties that can exploited on the development of advanced bionanomaterials. PMID- 27381584 TI - Physicochemical investigations of biogenic chitosan-silver nanocomposite as antimicrobial and anticancer agent. AB - Chitosan (CS), a seaweed polysaccharide is a natural macromolecule which is widely being used in medical applications because of its distinctive antimicrobial and anticancer properties. Silver, a noble metal, is also receiving wide attention for its potential usage in antimicrobial and anticancer therapeutics. In this study, an effective way of reduction of silver using chitosan at varying reaction temperatures and an optimised concentration of silver were performed. The optical, structural, spectral, morphological and elemental studies of the biosynthesized chitosan-silver (CS-Ag) nanocomposites were characterized by several techniques. The synthesized CS-Ag nanocomposites exhibit particle size around 20nm and were further exploited for potent biological applications in nanomedicine due to their nanometric sizes and biocompatibility of chitosan. The antimicrobial activity of the biosynthesized CS Ag nanocomposites exhibits zone of inhibition ranged between 09.666+/-0.577 and 19.000+/-1.000 (mm). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were from 8 to 128MUgmL-1 and 16 to 256MUgmL-1 respectively, with the highest antimicrobial activity shown against Gram-negative Salmonella sp. The synergistic effect of chitosan and silver as a composite in nanometric size revealed significant IC50 value of 29.35MUgmL-1 and a maximum of 95.56% inhibition at 100MUgmL-1 against A549 lung cancer cell line, resulting in potent anticancer effect. PMID- 27381585 TI - Development and evaluation of PLGA polymer based nanoparticles of quercetin. AB - Quercetin is the most abundant antioxidant found in the human diet. Low aqueous solubility of quercetin limits its bioavailability and hence therapeutic effects. Therefore, the aim of the present study was to develop a poly lactide-co-glycolic acid (PLGA) polymer based nanoparticles of quercetin with a view to improve its aqueous solubility and examine the effect on its antioxidant and diuretic properties. Nanoparticles of quercetin were developed by single emulsion-solvent evaporation technique and evaluated in vitro for differential scanning calorimetry (DSC), Fourier transforms infra-red (FTIR) spectroscopy, particle size, polydispersity index and drug entrapment efficiency. Among the five different formulations (F1, F2, F3, F4 and F5), F2 and F3 were optimized with an average particle size of 189nm and 186nm and high entrapment values of 86.48%, 83.71%, respectively. SEM images of confirmed that prepared nanoparticles were spherical in shape with a smooth surface. In vitro release and anti-oxidant activity confirmed significant results. Furthermore, its in vivo diuretic activity was much better as compared to pure quercetin. The overall results suggest that PLGA polymer based nanoparticle could be a potential option for quercetin delivery. PMID- 27381586 TI - Surfactant and metal ion effects on the mechanical properties of alginate hydrogels. AB - This paper addresses the controlled variation of the mechanical properties of alginate gel beads by changing the alginate concentration or by adding different surfactants or cross-linking cations. Alginate beads containing nonionic Brij 35 or anionic sodium dodecyl sulfate (SDS) surfactants were prepared with two different types of cations (Ca2+, Ba2+) as crosslinkers. Compression measurements were performed to investigate the effect of the surfactant and cation types and their concentrations on the Young's modulus of alginate beads. The Young's modulus was determined by using Hertz theory. For all types of alginate gel beads the Young's modulus showed an increasing value for increasing alginate contents. Addition of the anionic surfactant SDS increases the Young's modulus of the alginate beads while the addition of non-ionic surfactant Brij 35 leads to a decrease in Young's modulus. This opposite behavior is related to the contrary effect of both surfactants on the charge of the alginate beads. When Ba2+ ions were used as crosslinker cation, the Young's modulus of the beads with the surfactant SDS was found to be approximately two times higher than the modulus of beads with the surfactant Brij 35. An ion specific effect was found for the crosslinking ability of divalent cations. PMID- 27381587 TI - Protective roles of polysaccharides from Ganoderma lucidum on bleomycin-induced pulmonary fibrosis in rats. AB - The purpose of this paper was to investigate the protective effects of polysaccharides from (PGL) Ganoderma lucidum on bleomycin-induced pulmonary fibrosis in rats. Our study demonstrated that treatment with PGL of 100-300mg/kg for 28 days led to significant reduction in the pulmonary index, inflammatory cell infiltration and collagen deposition in rats with bleomycin-induced pulmonary fibrosis, which was associated with increased levels of glutathione, glutathione peroxidase, catalase and superoxide dismutase and decreased contents of malondialdehyde and hydroxyproline in the lung. These results indicated that PGL played a positive protective role in the pulmonary fibrosis and its possible mechanism was to improve lung antioxidant ability. PMID- 27381588 TI - Remote monitoring and heart failure: monitoring parameters, technology, and workflow. PMID- 27381589 TI - Cryoballoon or radiofrequency ablation for symptomatic paroxysmal atrial fibrillation: reintervention, rehospitalization, and quality-of-life outcomes in the FIRE AND ICE trial. AB - AIMS: The primary safety and efficacy endpoints of the randomized FIRE AND ICE trial have recently demonstrated non-inferiority of cryoballoon vs. radiofrequency current (RFC) catheter ablation in patients with drug-refractory symptomatic paroxysmal atrial fibrillation (AF). The aim of the current study was to assess outcome parameters that are important for the daily clinical management of patients using key secondary analyses. Specifically, reinterventions, rehospitalizations, and quality-of-life were examined in this randomized trial of cryoballoon vs. RFC catheter ablation. METHODS AND RESULTS: Patients (374 subjects in the cryoballoon group and 376 subjects in the RFC group) were evaluated in the modified intention-to-treat cohort. After the index ablation, log-rank testing over 1000 days of follow-up demonstrated that there were statistically significant differences in favour of cryoballoon ablation with respect to repeat ablations (11.8% cryoballoon vs. 17.6% RFC; P = 0.03), direct current cardioversions (3.2% cryoballoon vs. 6.4% RFC; P = 0.04), all-cause rehospitalizations (32.6% cryoballoon vs. 41.5% RFC; P = 0.01), and cardiovascular rehospitalizations (23.8% cryoballoon vs. 35.9% RFC; P < 0.01). There were no statistical differences between groups in the quality-of-life surveys (both mental and physical) as measured by the Short Form-12 health survey and the EuroQol five-dimension questionnaire. There was an improvement in both mental and physical quality-of-life in all patients that began at 6 months after the index ablation and was maintained throughout the 30 months of follow-up. CONCLUSION: Patients treated with cryoballoon as opposed to RFC ablation had significantly fewer repeat ablations, direct-current cardioversions, all-cause rehospitalizations, and cardiovascular rehospitalizations during follow-up. Both patient groups improved in quality-of-life scores after AF ablation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01490814. PMID- 27381591 TI - The Influence of School Nutrition Programs on the Weight of Low-Income Children: A Treatment Effect Analysis. AB - Recent policy attempts to set high nutrition standards for the School Breakfast Program (SBP) and National School Lunch Program (NSLP) aim to improve children's health outcomes. A timely and policy-relevant task evaluates to what extent school meal programs contribute to child body mass index (BMI) outcomes to assess those school meal policies' potential impacts. This study examines children's weight progress from 1st through 8th grade, while recognizing the potential effects on those children participating in both programs compared with those children participating in only one program. We used difference-in-differences (DID) and average treatment effect on the treated (ATT) methodologies and focused on free- and reduced-price meal-eligible children to filter out income effects. The DID results show that short-term participation in only NSLP increases the probability that children will be overweight, and these results are more prominent in the South, Northeast, and rural areas. ATT results show that participation in both programs from 1st through 8th grade increases the probability that these students will be overweight. With the Community Eligibility Provision having taken effect across the nation in the 2014-2015 school year, the need to continue examining the impacts of these programs on child BMI is even greater. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27381590 TI - Transient and chronic seizure-induced inflammation in human focal epilepsy. AB - In animal models, inflammation is both a cause and consequence of seizures. Less is known about the role of inflammation in human epilepsy. We performed positron emission tomography (PET) using a radiotracer sensitive to brain inflammation in a patient with frontal epilepsy ~36 h after a seizure as well as during a seizure free period. When statistically compared to a group of 12 matched controls, both of the patient's scans identified a frontal (supplementary motor area) region of increased inflammation corresponding to his clinically defined seizure focus, but the postseizure scan showed significantly greater inflammation intensity and spatial extent. These results provide new information about transient and chronic neuroinflammation in human epilepsy and may be relevant to understanding the process of epileptogenesis and guiding therapy. PMID- 27381592 TI - De Novo Synthesis of Furanose Sugars: Catalytic Asymmetric Synthesis of Apiose and Apiose-Containing Oligosaccharides. AB - A de novo synthetic method towards apiose, a structurally unusual furanose, is reported. The key feature is sequential metal catalysis consisting of the palladium-catalyzed asymmetric intermolecular hydroalkoxylation of an alkoxyallene and subsequent ring-closing metathesis (RCM). This strategy enabled the efficient synthesis of various apiose-containing disaccharides and a unique convergent synthesis of trisaccharides. PMID- 27381593 TI - Boston keratoprosthesis type I in the elderly. AB - BACKGROUND/AIMS: To determine the outcomes of Boston type I keratoprosthesis implanted in elderly patients. METHODS: A retrospective case series was performed on patients at least 75 years old who received the Boston type I keratoprosthesis between 1 January 2007 and 31 December 2012. Preoperative diagnosis, interval visual acuity, keratoprosthesis retention and postoperative complications were recorded for each patient. RESULTS: Forty-four Boston type I keratoprostheses were implanted in 44 eyes of 43 patients. The most common indication for surgery was corneal graft failure (n=23; 52.3%) followed by corneal scar (n=8; 18.2%) and limbal stem cell dysfunction (n=8; 18.2%). All patients had preoperative visual acuity of <=20/200. Thirty-six of 44 (82%) patients achieved visual acuity of 20/200 or better postoperatively, and 20 of those (55.6%) maintained 20/200 or better for 1 year after surgery. The median length of follow-up was 825 days (range: 27-2193 days), and at the last follow-up visit, 20 of 44 (45.5%) had 20/200 or better vision. The median best-corrected visual acuity (logMAR) improved from 2.6 preoperatively to 1.0 at 1 year postoperative (p<0.00001). Device retention at 1 year postoperative was 88.9%. The most common postoperative complications were retroprosthetic membrane formation in 20 patients (45.5%) and cystoid macular oedema in six patients (13.6%). One patient developed keratitis and consecutive endophthalmitis 2 months after surgery and required enucleation. CONCLUSIONS: Boston type I keratoprosthesis is an effective modality in corneal blindness in elderly patients. Failure to restore or maintain ambulatory vision was typically due to non-corneal comorbidities, often unrelated to the keratoprosthesis. PMID- 27381594 TI - Prominent Anti-UV Activity and Possible Cosmetic Potential of Lignin-carbohydrate Complex. AB - This review article summarizes the recent progress of ultraviolet rays (UV) protective substances, including our original reports. We have established a simple assay method for the determination of anti-UV activity that can be applicable to any kind of adherent cells. This method provides information of both anti-UV activity and cytotoxicity of any kind of samples even though those samples contain unknown amounts of test compounds. We found that lignin carbohydrate complex (LCC) showed one- or two-order higher anti-UV activity compared to well-known lower molecular weight polyphenols and hot-water extracts of Kampo medicines and tea leaves. Among synthetic compounds, water-soluble azulenes showed the highest anti-UV activity. LCC showed additive or synergistic anti-UV activity with vitamin C. Alkaline extract of Sasa senanensis Rehder leaves (SE), an LCC-rich over-the-counter (OTC) drug, also showed potent antiviral and vitamin C-synergized radical scavenging activity. SE has been utilized to manufacture tooth paste, soap and gel cosmetic to increase the level of quality of life (QOL). PMID- 27381595 TI - A Three-phase Approach for the Early Identification of Acute Lung Injury Induced by Severe Sepsis. AB - A number of studies have reported that acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are independent risk factors for organ dysfunction and mortality in patients with sepsis. Although ALI/ARDS might be an essential therapeutic target during the management of sepsis, severe sepsis should be treated effectively and as soon as identified. We have classified three phases, ranging from sepsis to organ dysfunction, characterizing the interaction between neutrophils and platelets. The first phase is neutrophil extracellular trap (NET) formation and intravasated platelet aggregation. The next phase is extravasated platelet aggregation (EPA), promoted by NET-facilitated detachment of endothelial cells. The final phase is organ dysfunction, caused by pulmonary veno-occlusive disease (VOD), fibrosis, and immunoparalysis induced by EPA. Severe sepsis is characterized by a continuum of coagulopathy, with coagulation abnormalities often developing before the onset of clinical symptoms. The initial medical treatment for ALI/ARDS is inhibition of NET formation and intravasated platelet aggregation to prevent endothelial cell damage (Phase 1). Beraprost and silvestat, phosphodiesterase 3 (PDE3) inhibitors, are often administered in clinical practice. To determine hypercoagulopathy, plasma levels of thrombin antithrombin complex and plasmin-plasmin inhibitor complex are continuously monitored in patients with suspected sepsis. Furthermore, the implementation of quality indicators for the early management of severe sepsis and septic shock is strongly associated with a reduced mortality. We conclude that pathophysiology of organ dysfunction from severe sepsis is caused by pulmonary VOD, fibrosis, and EPA-facilitated immunoparalysis. In order to prevent ALI/ARDS in patients with sepsis, countermeasures for NET and platelet aggregation should be pre-emptively employed and confirmed by several trials. PMID- 27381596 TI - Propeller Flaps: A Literature Review. AB - BACKGROUND/AIM: Since their introduction in 1991, propeller flaps are increasingly used as a surgical approach to loss of substance. The aim of this study was to evaluate the indications and to verify the outcomes and the complication rates using this reconstructing technique through a literature review. MATERIALS AND METHODS: A search on PubMed was performed using "propeller flap", "fasciocutaneous flap", "local flap" or "pedicled flap" as key words. We selected clinical studies using propeller flaps as a reconstructing technique. RESULTS: We found 119 studies from 1991 to 2015. Overall, 1,315 propeller flaps were reported in 1,242 patients. Most frequent indications included loss of substance following tumor excision, repair of trauma-induced injuries, burn scar contractures, pressure sores and chronic infections. Complications were observed in 281/1242 patients (22.6%) occurring more frequently in the lower limbs (31.8%). Partial flap necrosis and venous congestion were the most frequent complications. The complications' rate was significantly higher in infants (<10 years old) and in the older population (>70 years old) but there was not a significant difference between the sexes. Trend of complication rate has not improved during the last years. CONCLUSION: Propeller flaps showed a great success rate with low morbidity, quick recovery, good aesthetic outcomes and reduced cost. The quality and volume of the transferred soft tissue, the scar orientation and the possibility of direct donor site closure should be considered in order to avoid complications. Indications for propeller flaps are small- or medium-sized defects located in a well-vascularized area with healthy surrounding tissues. PMID- 27381597 TI - Clinical and Molecular Features of Laron Syndrome, A Genetic Disorder Protecting from Cancer. AB - Laron syndrome (LS) is a rare, genetic disorder inherited in an autosomal recessive manner. The disease is caused by mutations of the growth hormone (GH) gene, leading to GH/insulin-like growth factor type 1 (IGF1) signalling pathway defect. Patients with LS have characteristic biochemical features, such as a high serum level of GH and low IGF1 concentration. Laron syndrome was first described by the Israeli physician Zvi Laron in 1966. Globally, around 350 people are affected by this syndrome and there are two large groups living in separate geographic regions: Israel (69 individuals) and Ecuador (90 individuals). They are all characterized by typical appearance such as dwarfism, facial phenotype, obesity and hypogenitalism. Additionally, they suffer from hypoglycemia, hypercholesterolemia and sleep disorders, but surprisingly have a very low cancer risk. Therefore, studies on LS offer a unique opportunity to better understand carcinogenesis and develop new strategies of cancer treatment. PMID- 27381598 TI - Renal Subcapsular Space of Balb/c Nude Mice as a Route for Evaluating Subpopulations of Human Bladder Carcinoma Cells. AB - BACKGROUND/AIM: Subpopulations of bladder cancer (BC) cells have been found in tumors, with different abilities for malignancy and chemotherapy resistance. The BC cell line T24 has frequently been used to evaluate this phenomenon. Since technical limits exist in orthotopic procedures, we evaluated the renal subcapsular space as an alternative route for analyzing subpopulations of T24 BC cells in vivo. MATERIALS AND METHODS: Balb/c nude mice underwent renal subcapsular inoculation with T24 cells, suspended in two different volumes of PBS. Four weeks post-inoculation, histology and immunohistochemistry were carried out. RESULTS: In all the animals inoculated with a 10 MUl volume of suspended cells, a pseudo-bladder structure in the renal subcapsular space was observed, with differential expression of mesenchymal and epithelial markers. T24 cells infiltrating the renal parenchyma towards the medulla and vessels were also observed. The volume used for inoculation was an important factor for the success of this technique. CONCLUSION: Renal subcapsular inoculation is an effective route for analyzing subpopulations and differentiation of T24 cells. PMID- 27381599 TI - Making ICSI Safer and More Effective: A Review of the Human Oocyte and ICSI Practice. AB - Intracytoplasmic sperm injection (ICSI) has become an indispensable procedure of every assisted reproduction unit. This has created as much controversy as it has awe. As this is a multistep invasive technique, every part of the procedure has become subject to investigation. We contribute this review aspiring to offer the embryologist insight into all available approaches of securing an effective ICSI practice. Herein we present all the different approaches with respect to handling of the human oocyte, taking into consideration the important steps of the technique such as the oocyte positioning, timing of performing ICSI, the option of viewing the meiotic spindle and further individual action such as artificial oocyte activation, rescue ICSI and in vitro maturation. We enrich this by including our view based on our collective experience and current practice. Published studies have led to various options for performing ICSI, resulting in in vitro fertilization units around the world adopting different approaches. The steps that ICSI technique entails discussed from the oocyte perspective are still a long way from being organized into one secure and optimal protocol. Our stressing of the need to secure an efficient ICSI protocol could be the trigger for further well-designed larger scale studies with all the latest technological advantages. We aim to approach this subject in categories and assess them separately. However, ICSI is a multifaceted procedure involving several consecutive steps and when evaluating one we cannot exclude the end effect of the previous, or the overall effect of the different practitioners involved form beginning to end. PMID- 27381600 TI - Development of Critical-size Abdominal Defects in a Rabbit Model to Mimic Mature Ventral Hernias. AB - BACKGROUND/AIM: Mesh hernioplasty is one of the most frequently performed procedures in the United States. Abdominal rigidity and chronic inflammation, among other factors, contribute to long-term complications including chronic pain, abdominal wall stiffness and fibrosis. Acute models do not replicate the chronic environment associated with most hernias, limiting the ability to improve products. The present study details development of a critical-size defect in rabbit abdominal wall for maturation into a chronic hernia to enable analysis of hernia repair devices in a realistic environment. MATERIALS AND METHODS: New Zealand White Rabbits were used to assess defect creation and mature hernia development through a period of 21-35 days. RESULTS AND CONCLUSION: Through this study, a critical-size defect was developed based on 3-cm full-thickness incision through musculature and peritoneum followed by simple skin closure and wound maturation, which was identified as a reliable procedure for creating defects presenting typical aspects of mature hernias including hernia ring and adhesions. PMID- 27381601 TI - Simvastatin Inhibits Epithelial-to-Mesenchymal Transition Through Induction of HO 1 in Cultured Renal Proximal Tubule Cells. AB - BACKGROUND/AIM: Studies have shown that simvastatin (SIM) inhibits epithelial mesenchymal transition (EMT), a key step in fibrosis, and activates the anti fibrotic heme oxygenase-1 (HO-1) gene in renal proximal tubule cells independent of its lipid-lowering. We tested the hypothesis that SIM inhibits EMT via HO-1 dependent suppression of reactive oxygen species (ROS) release. MATERIALS AND METHODS: Renal proximal tubule cells were treated with either 10 MUM SIM or 10 ng/ml transforming growth factor-beta1 (TGFbeta1) or with their combination and promoter activity of the alpha-smooth muscle actin (alpha-SMA) gene, stress fiber formation (markers of EMT), as well as ROS production were determined. HO-1 was manipulated via genetic and pharmacologic means. RESULTS: SIM prevented TGFbeta1 dependent EMT and ROS production. Inhibition/knockdown of HO-1 reversed, while induction/overexpression of HO-1 emulated beneficial effects of SIM. CONCLUSION: SIM, via HO-1, suppresses TGFbeta1-dependent ROS production and, hence, EMT. Further evaluation of the anti-fibrotic nature of SIM in the kidney would be useful in the treatment of chronic kidney disease. PMID- 27381602 TI - In Vitro Study of a Liposomal Curcumin Formulation (LipocurcTM): Toxicity and Biological Activity in Synovial Fibroblasts and Macrophages. AB - BACKGROUND/AIM: The polyphenol curcumin is produced in the rhizome of Curcuma longa and exhibits potent anti-inflammatory, antioxidant, and chemopreventive activities. Due to the fact that curcumin is poorly soluble in water, many delivery systems have been developed to improve its solubility and bioavailability achieving optimum therapeutic application. In this study, we evaluated the biological effects of a liposomal curcumin formulation (LipocurcTM) on human synovial fibroblasts (SW982) and mouse macrophages (RAW264). MATERIAL AND METHODS: Cellular uptake of liposomes was studied using calcein-loaded liposomes. Effects of LipocurcTM on cell viability and proliferation were determined with Celltox green cytotoxicity assay and 2,3-bis-(2-methoxy-4-nitro-5 sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay, respectively. To induce cytokine/chemokine expression, the cells were stimulated with interleukin (IL)1beta or lipopolysaccharide (LPS). The release of IL6, IL8, and tumor necrosis factor-alpha (TNFalpha) was quantified by enzyme-linked immunosorbent assay (ELISA). RESULTS: Data showed that the liposomal curcumin formulation LipocurcTM was significantly less toxic to synovial fibroblasts and macrophages compared to non-encapsulated, free curcumin. Furthermore, LipocurcTM effectively reduced pro-inflammatory cytokine/chemokine expression in synovial fibroblasts as well as in macrophages without affecting cell viability, suggesting that this curcumin nanoformulation might be a promising tool for the treatment of inflammatory diseases. PMID- 27381603 TI - Synergism of Alkaline Extract of the Leaves of Sasa senanensis Rehder and Antiviral Agents. AB - BACKGROUND: Previous studies have shown a much greater antiviral activity of alkaline extract of the leaves of Sasa senanensis Rehder (SE) against human immunodeficiency virus (HIV), compared to lignin precursors, tannins and flavonoids, suggesting its possible application to oral diseases. Systematic comparative study with herpes simplex virus (HSV) has been limited compared to that with HIV. In the present study, we investigated whether combination of SE with other popular antiviral agents further enhances their individual activity. MATERIALS AND METHODS: Cell viability of mock-infected, HIV-infected and HSV infected cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) method. The antiviral activity was evaluated by the selectivity index, defined as the ratio of 50% cytotoxic concentration to 50% effective concentration. Synergy between SE and antiviral agents was evaluated by MacSynerg and CompuSyn software. RESULTS: SE showed potent anti-HIV activity, although its activity was two-orders lower than that of azidothymidine, 2',3' dideoxycytidine dextran sulfate and curdlan sulfate. Combination of SE with these antiviral agents produced synergistic effects. Using a newly established MTT assay system for anti-HSV activity, SE and acyclovir were found to have synergistic anti-HSV activity. CONCLUSION: The present study suggests the possible efficacy of the clinical application of SE combined with antiviral agents. PMID- 27381604 TI - Graft-versus-Host Disease in a Dog After Reduced-intensity Hematopoietic Stem Cell Transplantation from a DLA-identical Littermate. AB - BACKGROUND: Graft-versus-host disease (GvHD) is an adverse effect following hematopoietic stem cell transplantation (HSCT) in humans. Dogs represent a key model organism for the development of treatment protocols for HSCT. However, detailed descriptions of canine GvHD and its treatment are rare. Herein we describe the development of canine GvHD and therapeutic intervention. MATERIALS AND METHODS: A female Beagle received an allogeneic HSCT from a dog leukocyte antigen-identical littermate (conditioning with 4.5 Gy total body irradiation; immunosuppression with cyclosporine A). RESULTS: GvHD developed at day +52 and was treated with methylprednisolone, cyclosporine A, antibiotics, antiviral medication and analgesics. The dog initially responded to the treatment but GvHD relapsed twice. Within one week after discontinuation of glucocorticoid, GvHD recurred resulting in inevitable euthanasia of the animal. CONCLUSION: GvHD represents a life-threatening disease after HSCT in canines. Immediate therapeutic treatment is indicated and even a successful initial treatment response does not necessarily prevent GvHD recurrence. PMID- 27381605 TI - Inhibitory Effects of Medium Molecular Weight Heparinyl Amino Acid Derivatives on Ischemic Paw Edema in Mice. AB - We investigated the radical-scavenging effects of heparin (HE), medium molecular weight heparinyl phenylalanine (MHF), and medium molecular weight heparinyl leucine (MHL) using ischemic paw edema in mice. We also examined the activated partial thromboplastin time (APTT) of mice that were administered these compounds as an index of their side-effects. HE had a preventative effect and significant reduced ischemic paw edema. However, its effect was not dose-dependent and the dose-response curve was bell-shaped. The effective dose of HE also exhibited a prolonged APTT. Pretreatment using MHF and MHL were effective against ischemic paw edema without a prolonged APTT. Remarkably, the action of MHF was not only preventively, but also therapeutically active. These results suggest that MHF and MHL are superior to HE as safe radical scavengers in vivo. PMID- 27381606 TI - The Contribution of Matrix Metalloproteinase-1 Genotype to Oral Cancer Susceptibility in Taiwan. AB - AIM: Metalloproteinases (MMPs) are a family of multifunctional proteins which have been shown to be up-regulated in various types of cancer. However, the contribution of MMP1 genotype to oral cancer has not been elucidated. This study aimed to evaluate the contribution of MMP1 promoter 1607 genotype to the risk of oral cancer. MATERIALS AND METHODS: In this case-control study, MMP1 genotype and its interaction with consumption of areca, cigarettes, and alcohol in determining oral cancer risk were investigated in 788 patients with oral cancer and 956 gender-matched healthy controls. RESULTS: The distribution of 2G/2G, 1G/2G and 1G/1G for MMP1 promoter 1607 genotype was 36.8%, 40.2% and 23.0% in the oral cancer group and 34.3%, 44.9% and 20.8% in the non-cancer control group, respectively (p for trend=0.1454). We also analyzed the allelic frequency distributions and found that the variant 1G allele of MMP1 promoter 1607 conferred similar oral cancer susceptibility as the wild-type 2G allele (odds ratio=0.99, 95% confidence interval=0.87-1.14, p=0.9199). As for the gene lifestyle interaction, there was an obvious protective effect of MMP1 promoter 1607 1G/2G genotype on the risk of oral cancer among smokers (odds ratio=0.71, 95% confidence interval=0.55-0.91, p=0.0076), but not non-smokers. There was no interaction between MMP1 promoter 1607 genotype and areca chewing or alcohol drinking habits. CONCLUSION: The 1G/2G genotype of MMP1 promoter 1607 may have a protective effect on oral cancer risk for smokers. The detailed mechanisms involved in this require further investigation. PMID- 27381607 TI - Dietary Protective Effects Against Hepatocellular Carcinoma Development in Mdr2-/ Knockout Mice. AB - BACKGROUND/AIM: The Mdr2(-/-) mouse develops early chronic cholestatic hepatitis and hepatocellularcarcinoma (HCC) when adult. We tested the effects of a restricted-calorie diet on HCC development in Mdr2(-/-) mice. MATERIALS AND METHODS: Mdr2(-/-) mice (n=40, divided into two groups of 20 mice each) were randomized to receive ad libitum diet or restricted-calorie diet. Two mice from each group were sacrificed at 3 and 6 months, and liver tissue samples were removed for analysis. The remaining mice were fed their respective diets until the age of 30 months, at which time they were euthanized and livers were collected for analysis. RESULTS: The restricted-calorie diet had partial chemopreventive effect on the development of HCC in Mdr2(-/-) mice. Moreover, mice with ad libitum diet had a median survival of 361 days, while the restricted calorie group had a median survival of 500 days (p=0.0001). CONCLUSION: A restricted diet might reduce the chance of developing HCC in patients at risk and could increase the protective action of anti-inflammatory agents. PMID- 27381608 TI - Impact of Superoxide Dismutase-Gliadin on Radiation-induced Fibrosis: An Experimental Study. AB - AIM: Radiation-induced fibrosis (RIF) has since long been considered as irreversible. Further understanding of its mechanisms has led to trials investigating RIF treatment and prevention. The effect of superoxide dismutase (SOD)-gliadin, an oral form of SOD that resists gastrointestinal inactivation, on RIF treatment was evaluated in this experimental study. MATERIALS AND METHODS: A total of 36 Wistar albino mice were randomly distributed into four groups. According to group, 25 Gy radiation or sham-radiation were performed on day 0. Acute and late reactions were recorded. After 6 months, mice were treated with SOD-gliadin, 10,000 units per kg per day, or placebo. SOD-gliadin and placebo treatments were administered daily for 8 days by oral gavage. Later the mice were sacrificed, dissected and histopathologically analyzed. Accumulated hyaline and collagen at the dermis is an indicator of fibrosis. Therefore measurements of the dermal thickness were used to quantify the degree of RIF. Additionally, the morphological changes were analyzed, and the differences reported. RESULTS: The mean and standard deviation for dermal thickness were 0.45+/-0.09 mm in the sham irradiated placebo-treated group, 0.51 mm+/-0.16 mm in the sham-irradiated SOD gliadin-treated group, 0.92 mm+/-0.23 mm in the irradiated placebo-treated group and 0.71 mm+/-0.17 mm in the irradiated SOD-gliadin-treated group. The difference in mean dermal thickness between irradiated placebo-treated and irradiated SOD gliadin-treated mice was statistically significant (p=0.002). CONCLUSION: Quality of life while prolonging survival has an increasing importance in patients with cancer. RIF can be a crucial problem after all radiotherapy modalities. SOD gliadin has advantageous effects on conditions that call for an increased expression of antioxidant enzymes. The results of our study suggest that oral SOD gliadin may prevent or ameliorate RIF and patients can benefit from the positive effects of SOD. PMID- 27381609 TI - Apoptosis-inducing Effect of a Palladium(II) Complex-[PdCl(terpy)](sac).2H2O] on Ehrlich Ascites Carcinoma (EAC) in Mice. AB - BACKGROUND/AIM: New compounds for cancer treatment are needed due to persistenly unsatisfactory management of cancer. [PdCl(terpy)](sac).2H2O] (sac=saccharinate, and terpy=2,2':6',2"-terpyridine) is a compound synthesized for this purpose. We investigated its anti-proliferative and pro-apoptotic effects on Ehrlich Ascites Carcinoma (EAC) in vivo. MATERIALS AND METHODS: 42 Balb-c female mice were subcutaneously (s.c.) injected with EAC cells (1st day) and then randomly divided into 5 groups: control (0.9% NaCl), complex (2 mg/kg), complex (3 mg/kg) cisplatin (4 mg/kg) and paclitaxel (12.5 mg/kg). On the 5th and 12th day animals were drug administrated. At 14th day, animals were sacrificed. Expression of cell death and/or cell cycle-related markers (Bcl-2, Bax, active caspase-3, p53, PCNA) and apoptosis were investigated immunohisto-chemically. Survival-related markers (Akt, GSK-3beta, IGF-1R, IR, IRS-1, p70S6K, PRAS40) were evaluated by luminex analysis. RESULTS: Expression of p53, PCNA, Bcl-2 was found decreased (p<0.001) and that of active caspase-3, Bax, and apoptotic cells was found increased (p<0.001) in all groups. The survival-related markers did not show any statistical difference in complex groups. CONCLUSION: The Pd(II)-complex seems to have a strong anticancer activity on EAC by inducing apoptosis via both suppression of proliferation and activation of apoptosis in vivo, similar to the effects of cisplatin and paclitaxel. PMID- 27381610 TI - Ultrasonography as the Gold Standard for In Vivo Volumetric Determination of Chemically-induced Mammary Tumors. AB - BACKGROUND/AIM: In this study, we evaluated the dimensions and volume of rat mammary tumors and the association of these variables with tumor invasiveness. MATERIALS AND METHODS: Tumors were measured by caliper and ultrasonography. Volume was determined by water displacement and by application of four formulas using tumor length (L), width (W) and depth (D) or tumor weight. RESULTS: Results confirmed the data obtained in our previous work, where we verified that mammary tumors grow as oblate spheroids. CONCLUSION: The determination of mammary tumor volume by applying the formula V=(4/3)*pi*(L/2)*(L/2)*(D/2) is the best way to evaluate tumor volume in vivo. Beyond volume evaluation by water displacement, the determination on the basis of tumor weight is the most accurate way to evaluate tumor volume after animal sacrifice or tumor excision. According to our results, it is not possible to predict if a tumor is invasive or non-invasive by its dimensions, volume or weight. Future work in chemically-induced mammary cancer should use ultrasonography and water displacement or tumor weight to determine tumor volume in vivo and after animal sacrifice or tumor excision, respectively. PMID- 27381611 TI - Polymorphism Analysis of GSTM1 and OPA1 Genes in Greek Patients with Primary Open angle Glaucoma. AB - BACKGROUND: Glaucoma is a heterogenous group of optic neuropathies leading to progressive degeneration of the optic nerve and vision loss. Over the past decades, disease-causing genes have been identified and multigenic inheritance theory has-beens investigated for many cases of glaucoma. The purpose of this study was to investigate the distribution of mutations in glutathione S transferase M1 (GSTM1) and optic atrophy 1 (OPA1) genes in a series of patients of Greek origin. PATIENTS AND METHODS: This was a case-control study of 106 patients with primary open-angle glaucoma (POAG) and 120 healthy controls of Greek origin, surveyed for polymorphisms with potential correlation to POAG. A DNA sample from each individual was genotyped for GSTM1 and OPA1 (rs166850, rs10451941) polymorphisms. RESULTS: GSTM1 null genotype carriers seem to have an increased risk of developing POAG (odds ratio=1.86, 95% confidence interval=1.07 3.21; p=0.03). The results indicate that the OPA1 genotype (rs166850 and rs10451941 polymorphisms) is not significantly associated with POAG. CONCLUSION: The GSTM1 null genotype might be associated with increased risk of development of POAG in the Greek population. No significant correlation was found between OPA1 polymorphisms and POAG. PMID- 27381613 TI - Association of CTLA4 and CD28 Gene Variants and Circulating Levels of Their Proteins in Patients with Breast Cancer. AB - BACKGROUND/AIM: Breast cancer is one of the most common and lethal types of cancer among women. We focused on the importance of the immune system in the etiology of breast cancer by investigating critical polymorphisms of cytotoxic T lymphocyte-associated protein 4 (CTLA4) and cluster of differentiation 28 (CD28) gene, and circulating levels of these proteins. MATERIALS AND METHODS: A total of 79 patients with breast cancer and 76 healthy controls were enrolled. Molecular assessment of CTLA4 (rs231775&rs5742909) and CD28 (rs3116496) variants were determined with polymerase chain reaction restriction fragment length polymorphism techniques. Circulating levels of soluble forms of CTLA4 and CD28 were analyzed by ELISA. RESULTS: Although no significant association was found between study groups, CTLA4 +49AA genotypic frequency, and sCTLA4 and sCD28 levels were higher in patients. Some clinicopathological features were also related with CTLA4 and CD28 variants and blood levels. CONCLUSION: While CTLA4 +49AA genotype is increased in patients with breast cancer, the CTLA4 -318T allele may have a prognostic value. In addition, sCTLA4 and sCD28 can be used for diagnostic purposes in patients with breast cancer. PMID- 27381612 TI - Evaluation of a Non-aqueous Ibuprofen-Phospholipid Complex Formulation in Rats. AB - AIM: In the present study, a non-aqueous ibuprofen-phospholipid complex was developed to reduce the gastrointestinal (GI) toxicity of ibuprofen. MATERIALS AND METHODS: A non-aqueous ibuprofen-phospholipid complex (IBU-PC) was prepared by mixing phosal-35SB and ibuprofen. In vitro release behavior was studied using a dissolution apparatus. Irritation to gastrointestinal (GI) tract and pharmacokinetics of IBU-PC were studied in rats. RESULTS: Rapid release of drug occurred with approximately 85% of ibuprofen released from the composition within the first 30 min. The GI injury in IBU-PC-treated rats was minimal compared to those of Advil Liqui-gels-treated group. There was no significant difference between IBU-PC and Motrin-treated groups. The area under the concentration-time curve (AUC0~24) of IBU-PC and Motrin were 366+/-115 and 391+/-105 MUg/h/ml, respectively. The relative bioavailability of IBU-PC was 94.2%. CONCLUSION: IBU PC can decrease GI adverse reaction induced by ibuprofen. PMID- 27381614 TI - Short MRI Protocol for Excluding Traumatic Lesions of the Scaphoid Bone in Children. AB - BACKGROUND/AIM: Management of scaphoid trauma includes imaging with repeated X rays whose interpretation is difficult and often ambivalent. The aim of the study was to propose a fast magnetic resonance imaging (MRI) protocol permitting exclusion of traumatic lesions of the scaphoid bone in children, which would avoid unnecessary immobilization and irradiation in negative cases. PATIENTS AND METHODS: Two pediatric radiologists retrospectively reviewed the X-rays and MRIs of 45 children with clinical suspicion of scaphoid trauma. X-Rays and MRI sequences [short tau inversion recovery (STIR), T1] were scored as: 0 (negative) or 1 (equivocal or positive). X-ray results were compared to those of MRI and interobserver reliability was measured for both methods. RESULTS: MRI was shown to be more reliable than X-ray in excluding pediatric traumatic scaphoid lesions. X-Ray results differed significantly between the two readers (p=0.0001), and the interobserver reliability was low (kappa=0.529). For MRI interpretation, there was no significant difference between the two readers' assessments. The interobserver reliability was high (kappa=0.9544) and only in one case was there discordance. Absence of scaphoid trauma was confirmed on MRI in 18 out of 45 patients. For these patients, immobilization was reconsidered and no follow-up X ray was performed. CONCLUSION: Early MRI is useful in the management of pediatric scaphoid trauma. A short MRI protocol consisting of a STIR and a T1 sequence is sufficient for differentiating positive from negative cases and gives a good negative predictive value for exclusion of a traumatic scaphoid lesion. PMID- 27381615 TI - Cooling Composite Graft for Distal Finger Amputation: A Reliable Alternative to Microsurgery Implantation. AB - BACKGROUND: Finger amputations are the most common injuries to the upper limb. There are many options in the management of fingertip or finger amputations. We report our experience using cooling composite graft (Hirase technique) for distal finger amputation, as alternative to microsurgery implantation. PATIENTS AND METHODS: We collected a case series of eight patients and report on the clinical outcomes after a 10-month follow-up period. RESULTS: The amputated part survived almost completely in six patients; in these cases, the fingertip amputations were classified, according to the Allen classification, as level I in two cases, level II in three cases and level III in one case. CONCLUSION: Re-implantation of an amputated finger with the Hirase technique is possible and can provide good distal soft-tissue coverage and recovery of sensory and motor functions. We believe that re-attachment of the amputated portion as a composite graft represents an important alternative to microsurgery. PMID- 27381616 TI - Predicting IVF Outcome: A Proposed Web-based System Using Artificial Intelligence. AB - AIM: To propose a functional in vitro fertilization (IVF) prediction model to assist clinicians in tailoring personalized treatment of subfertile couples and improve assisted reproduction outcome. MATERIALS AND METHODS: Construction and evaluation of an enhanced web-based system with a novel Artificial Neural Network (ANN) architecture and conformed input and output parameters according to the clinical and bibliographical standards, driven by a complete data set and "trained" by a network expert in an IVF setting. RESULTS: The system is capable to act as a routine information technology platform for the IVF unit and is capable of recalling and evaluating a vast amount of information in a rapid and automated manner to provide an objective indication on the outcome of an artificial reproductive cycle. CONCLUSION: ANNs are an exceptional candidate in providing the fertility specialist with numerical estimates to promote personalization of healthcare and adaptation of the course of treatment according to the indications. PMID- 27381617 TI - Although Non-diagnostic Between Necrosis and Recurrence, FDG PET/CT Assists Management of Brain Tumours After Radiosurgery. AB - AIM: To re-evaluate the role of (18)F-fluoro-deoxy-D-glucose (FDG) positron emission tomography/ computer assisted tomography (PET/CT) co-registered with magnetic resonance imaging (MRI) in differentiating adverse radiation effect (ARE) from tumour recurrence after Gamma Knife radiosurgery of brain tumours. PATIENTS AND METHODS: Twenty-seven PET/CT studies co-registered with MRI were performed on 16 patients after radiosurgery, with 12/16 patients having multiple radiosurgery treatments. Long term follow-up was used for evaluation, with 3/16 patients being histopathologically confirmed. RESULTS: PET/CT was positive in all studies in 6/16 patients, negative in all studies in 6/16 and changed from negative to positive in one. In 2/16 patients, PET/CT was both positive and negative in separate tumour foci. In 9/16 cases with a positive PET/CT, tumour was confirmed. In 6/16 patients with a negative PET/CT, 3/6 had recurrence and 3/6 ARE. In 1/16, equivocal results became negative after retreatment. PET/CT/MRI identified tumour within ARE. Sensitivity of PET/CT/MRI proved to be 64.7%, and specificity 100%. CONCLUSION: PET/CT/MRI assists management, by revealing metabolism rather than histology. PMID- 27381618 TI - Physical Training, Hemodynamic Parameters and Arterial Stiffness: Friends or Foes of the Hypertensive Patient? AB - AIM: To evaluate the impact of physical training on central hemodynamic parameters and elasticity of large arteries in hypertensive patients. PATIENTS AND METHODS: A total of 129 hypertensive patients were divided into two groups: group A followed lifestyle changes and physical training; and group B acted as a control group; seven parameters were recorded: Pulse wave velocity (PWVao), systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), central aortic systolic blood pressure (SBPao), aortic diastolic blood pressure (DBPao), and central aortic pulse pressure (PPao). RESULTS: The difference between values at 4 months and baseline (Delta) were as follows: DeltaPWVao was -1.02 m/s (p<0.001) versus 0.17 m/s (p=0.035), DeltaSBPao was -9.6 mmHg (p=0.009) versus 1.6 mmHg (p=0.064), and DeltaPPao was -6.8 mmHg (p<0.001) versus 3.2 mmHg, (p=0.029) in group A versus B, respectively. CONCLUSION: Exercise training improves SBP, PP, SBPao, PPao and may delay arterial ageing. PMID- 27381619 TI - Palliative Radiation Therapy for Spinal Cord Compression from Metastatic Soft Tissue Sarcoma. AB - AIM: Spinal cord compression (SCC) from metastatic soft tissue sarcoma is a rare condition. Little is known regarding its optimal treatment. It is not clear whether these patients should receive radiation therapy alone or neurosurgery plus radiation therapy. This study focused on outcomes of patients with SCC from soft tissue sarcoma after radiation therapy alone. PATIENTS AND METHODS: The effect of radiotherapy on pain relief and motor function and overall survival were evaluated in four patients. RESULTS: Complete pain relief was achieved in two (50%) and overall pain relief in three patients (75%). Motor function remained unchanged in all patients. Overall survival rates at three and six months following irradiation were 25% and 25%, respectively. CONCLUSION: Radiotherapy alone resulted in high rates of pain relief in patients with SCC from metastatic soft tissue sarcoma. The effect on motor function was less favorable. Upfront neurosurgery is required for improvement of motor deficits. PMID- 27381620 TI - Errata. PMID- 27381621 TI - Role of Simulation in Perioperative Echocardiography Training. AB - Echocardiography plays a major role in the diagnosis and management of hemodynamic compromise during the perioperative period. Both transthoracic and transesophageal echocardiography have been shown to improve outcomes after cardiac and noncardiac surgery. Teaching basic echocardiographic skills to perioperative physicians remains a challenging task. Thus far, simulation-based medical education has been proven useful in teaching specific procedural skills and management of infrequent catastrophic events. Simulation-based echocardiography education has the potential to facilitate clinical training in echocardiography. Several small studies have shown the benefits of echocardiographic simulation on developing psychomotor and cognitive echocardiography skills. Future research should focus on the impact of simulation on actual clinical echocardiographic performance in the operating room and ultimately, patient outcomes. PMID- 27381623 TI - Longitudinal Body Composition Changes in Diffuse Large B-cell Lymphoma Survivors: A Retrospective Cohort Study of United States Veterans. AB - BACKGROUND: Body composition parameters are associated with long-term health outcomes. We assessed longitudinal body composition changes in diffuse large B cell lymphoma (DLBCL) survivors and identified clinical variables associated with the long-term development of sarcopenia and visceral obesity. METHODS: A retrospective cohort of United States veterans with DLBCL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone, with or without rituximab, was assembled. Muscle, subcutaneous fat, and visceral fat areas were measured with computed tomography analysis. Data were analyzed with repeated measures analysis of variance and logistic regression. All statistical tests were two-sided. RESULTS: Three hundred forty-two patients were included. Muscle area initially decreased during treatment, then returned to baseline by 24 months after treatment. Subcutaneous fat area increased from baseline by 6.5% (95% confidence interval [CI] = 2.6% to 10.5%) during treatment and by 21.4% (95% CI = 15.7% to 27.2%) by 24 months after treatment. Visceral fat area increased from baseline by 4.5% (95% CI = -0.9% to 9.9%) during treatment and by 21.6% (95% CI = 14.8% to 28.4%) by 24 months after treatment. Variables associated with long-term development of sarcopenia included: baseline sarcopenia (adjusted odds ratio [aOR] = 17.21, 95% CI = 8.48 to 34.94), older than age 60 years (aOR = 2.93, 95% CI = 1.46 to 5.88), and weight loss greater than 5% during treatment (aOR = 2.40, 95% CI = 1.12 to 5.14). Variables associated with long-term visceral fat gain included: weight gain greater than 5% during treatment (aOR = 4.60, 95% CI = 2.42 to 8.74). CONCLUSIONS: DLBCL survivors undergo unfavorable long-term body composition changes. Patients at risk for the long-term development of sarcopenia or visceral obesity can be identified based on clinical risk factors and targeted for lifestyle interventions. PMID- 27381622 TI - Role of Myeloma-Derived MIF in Myeloma Cell Adhesion to Bone Marrow and Chemotherapy Response. AB - BACKGROUND: Multiple myeloma (MM) remains an incurable cancer characterized by accumulation of malignant plasma cells in the bone marrow (BM). The mechanism underlying MM homing to BM is poorly elucidated. METHODS: The clinical significance of migration inhibitory factor (MIF) expression was examined by analyzing six independent gene expression profile databases of primary MM cells using the Student's t test and Kaplan-Meier test. Enzyme-linked immunosorbent assay was used to examine MIF expression. In vivo bioluminescent imaging was used to determine MM cell localization and treatment efficacy in human MM xenograft mouse models, with three to four mice per group. MM cell attachment to BM stromal cells (BMSCs) was monitored by cell adhesion assay. MIF regulation of the expression of adhesion molecules was determined by chromatin immunoprecipitation (ChIP) assay. Statistical tests were two-sided. RESULTS: High levels of MIF were detected in MM BM (MIF level in BM plasma: healthy = 10.72 +/- 5.788 ng/mL, n = 5; MM = 1811 +/- 248.7 ng/mL, n = 10; P < .001) and associated with poor survival of patients (Kaplan-Meier test for MM OS: 87 MIF(high) patients, 86 MIF(low) patients, P = .02). Knocking down MIF impaired MM cell adhesion to BMSCs in vitro and led to formation of extramedullary tumors in SCID mice. MIF acted through surface receptor CXCR4 and adaptor COPS5 to regulate the expression of adhesion molecules ALCAM, ITGAV, and ITGB5 on MM cells. More importantly, MIF-deficient MM cells were sensitive to chemotherapy in vitro when cocultured with BMSCs and in vivo. MIF inhibitor 4-IPP sensitized MM cells to chemotherapy. CONCLUSIONS: MIF is an important player and a novel therapeutic target in MM. Inhibiting MIF activity will sensitize MM cells to chemotherapy. PMID- 27381625 TI - Ethnic Variations in Estrogen and Its Metabolites: Sufficient to Explain Differences in Breast Cancer Incidence Rates? PMID- 27381624 TI - The Doppelganger Effect: Hidden Duplicates in Databases of Transcriptome Profiles. AB - Whole-genome analysis of cancer specimens is commonplace, and investigators frequently share or re-use specimens in later studies. Duplicate expression profiles in public databases will impact re-analysis if left undetected, a so called "doppelganger" effect. We propose a method that should be routine practice to accurately match duplicate cancer transcriptomes when nucleotide-level sequence data are unavailable, even for samples profiled by different microarray technologies or by both microarray and RNA sequencing. We demonstrate the effectiveness of the method in databases containing dozens of datasets and thousands of ovarian, breast, bladder, and colorectal cancer microarray profiles and of matching microarray and RNA sequencing expression profiles from The Cancer Genome Atlas (TCGA). We identified probable duplicates among more than 50% of studies, originating in different continents, using different technologies, published years apart, and even within the TCGA itself. Finally, we provide the doppelgangR Bioconductor package for screening transcriptome databases for duplicates. Given the potential for unrecognized duplication to falsely inflate prediction accuracy and confidence in differential expression, doppelganger checking should be a part of standard procedure for combining multiple genomic datasets. PMID- 27381627 TI - David Oliver: Celebrating the expert generalist. PMID- 27381626 TI - Mechanisms of Therapy Resistance in Patient-Derived Xenograft Models of BRCA1 Deficient Breast Cancer. AB - BACKGROUND: Although BRCA1-deficient tumors are extremely sensitive to DNA damaging drugs and poly(ADP-ribose) polymerase (PARP) inhibitors, recurrences do occur and, consequently, resistance to therapy remains a serious clinical problem. To study the underlying mechanisms, we induced therapy resistance in patient-derived xenograft (PDX) models of BRCA1-mutated and BRCA1-methylated triple-negative breast cancer. METHODS: A cohort of 75 mice carrying BRCA1 deficient breast PDX tumors was treated with cisplatin, melphalan, nimustine, or olaparib, and treatment sensitivity was determined. In tumors that acquired therapy resistance, BRCA1 expression was investigated using quantitative real time polymerase chain reaction and immunoblotting. Next-generation sequencing, methylation-specific multiplex ligation-dependent probe amplification (MLPA) and Target Locus Amplification (TLA)-based sequencing were used to determine mechanisms of BRCA1 re-expression in therapy-resistant tumors. RESULTS: BRCA1 protein was not detected in therapy-sensitive tumors but was found in 31 out of 42 resistant cases. Apart from previously described mechanisms involving BRCA1 intragenic deletions and loss of BRCA1 promoter hypermethylation, a novel resistance mechanism was identified in four out of seven BRCA1-methylated PDX tumors that re-expressed BRCA1 but retained BRCA1 promoter hypermethylation. In these tumors, we found de novo gene fusions that placed BRCA1 under the transcriptional control of a heterologous promoter, resulting in re-expression of BRCA1 and acquisition of therapy resistance. CONCLUSIONS: In addition to previously described clinically relevant resistance mechanisms in BRCA1-deficient tumors, we describe a novel resistance mechanism in BRCA1-methylated PDX tumors involving de novo rearrangements at the BRCA1 locus, demonstrating that BRCA1 methylated breast cancers may acquire therapy resistance via both epigenetic and genetic mechanisms. PMID- 27381628 TI - Identifying Communication-Impaired Pediatric Patients Using Detailed Hospital Administrative Data. AB - BACKGROUND AND OBJECTIVES: Pediatric inpatients with communication impairment may experience inadequate pain and symptom management. Research regarding potential variation in care among patients with and without communication impairment is hampered because existing pediatric databases do not include information about patient communication ability per se, even though these data sets do contain information about diagnoses and medical interventions that are probably correlated with the probability of communication impairment. Our objective was to develop and evaluate a classification model to identify patients in a large administrative database likely to be communication impaired. METHODS: Our sample included 236 hospitalized patients aged >=12 months whose ability to communicate about pain had been assessed. We randomly split this sample into development (n = 118) and validation (n = 118) sets. A priori, we developed a set of specific diagnoses, technology dependencies, procedures, and medications recorded in the Pediatric Health Information System likely to be strongly associated with communication impairment. We used logistic regression modeling to calculate the probability of communication impairment for each patient in the development set, assessed the model performance, and evaluated the performance of the 11-variable model in the validation set. RESULTS: In the validation sample, the classification model showed excellent classification accuracy (area under the receiver operating characteristic curve 0.92; sensitivity 82.6%; 95% confidence interval, 74%-100%; specificity 86.3%; 95% confidence interval, 80%-97%). For the complete sample, the predicted probability of communication impairment demonstrated excellent calibration with the observed communication impairment status. CONCLUSIONS: Hospitalized pediatric patients with communication impairment can be accurately identified in a large hospital administrative database. PMID- 27381629 TI - Erratum to: Genome-wide Identification and analysis of the stress-resistance function of the TPS (Trehalose-6-Phosphate Synthase) gene family in cotton. PMID- 27381630 TI - Intrusive effects of semantic information on visual selective attention. AB - Every object is represented by semantic information in extension to its low-level properties. It is well documented that such information biases attention when it is necessary for an ongoing task. However, whether semantic relationships influence attentional selection when they are irrelevant to the ongoing task remains an open question. The ubiquitous nature of semantic information suggests that it could bias attention even when these properties are irrelevant. In the present study, three objects appeared on screen, two of which were semantically related. After a varying time interval, a target or distractor appeared on top of each object. The objects' semantic relationships never predicted the target location. Despite this, a semantic bias on attentional allocation was observed, with an initial, transient bias to semantically related objects. Further experiments demonstrated that this effect was contingent on the objects being attended: if an object never contained the target, it no longer exerted a semantic influence. In a final set of experiments, we demonstrated that the semantic bias is robust and appears even in the presence of more predictive cues (spatial probability). These results suggest that as long as an object is attended, its semantic properties bias attention, even if it is irrelevant to an ongoing task and if more predictive factors are available. PMID- 27381631 TI - On the relationship between response selection and response inhibition: An individual differences approach. AB - The abilities to select appropriate responses and suppress unwanted actions are key executive functions that enable flexible and goal-directed behavior. However, to date it has been unclear whether these two cognitive operations tap a common action control resource or reflect two distinct processes. In the present study, we used an individual differences approach to examine the underlying relationships across seven paradigms that varied in their response selection and response inhibition requirements: stop-signal, go-no-go, Stroop, flanker, single response selection, psychological refractory period, and attentional blink tasks. A confirmatory factor analysis suggested that response inhibition and response selection are separable, with stop-signal and go-no-go task performance being related to response inhibition, and performance in the psychological refractory period, Stroop, single-response selection, and attentional blink tasks being related to response selection. These findings provide evidence in support of the hypothesis that response selection and response inhibition reflect two distinct cognitive operations. PMID- 27381632 TI - Perceived empty duration between sounds of different lengths: Possible relation with repetition and rhythmic grouping. AB - We investigated how perceived duration of empty time intervals would be modulated by the length of sounds marking those intervals. Three sounds were successively presented in Experiment 1. Each sound was short (S) or long (L), and the temporal position of the middle sound's onset was varied. The lengthening of each sound resulted in delayed perception of the onset; thus, the middle sound's onset had to be presented earlier in the SLS than in the LSL sequence so that participants perceived the three sounds as presented at equal interonset intervals. In Experiment 2, a short sound and a long sound were alternated repeatedly, and the relative duration of the SL interval to the LS interval was varied. This repeated sequence was perceived as consisting of equal interonset intervals when the onsets of all sounds were aligned at physically equal intervals. If the same onset delay as in the preceding experiment had occurred, participants should have perceived equality between the interonset intervals in the repeated sequence when the SL interval was physically shortened relative to the LS interval. The effects of sound length seemed to be canceled out when the presentation of intervals was repeated. Finally, the perceived duration of the interonset intervals in the repeated sequence was not influenced by whether the participant's native language was French or Japanese, or by how the repeated sequence was perceptually segmented into rhythmic groups. PMID- 27381633 TI - Metastatic insular thyroid carcinoma masquerades as neuroendocrine tumor in lung on CT-guided fine needle aspiration biopsy. PMID- 27381634 TI - Envelope-specific B-cell populations in African green monkeys chronically infected with simian immunodeficiency virus. AB - African green monkeys (AGMs) are natural primate hosts of simian immunodeficiency virus (SIV). Interestingly, features of the envelope-specific antibody responses in SIV-infected AGMs are distinct from that of HIV-infected humans and SIV infected rhesus monkeys, including gp120-focused responses and rapid development of autologous neutralization. Yet, the lack of genetic tools to evaluate B-cell lineages hinders potential use of this unique non-human primate model for HIV vaccine development. Here we define features of the AGM Ig loci and compare the proportion of Env-specific memory B-cell populations to that of HIV-infected humans and SIV-infected rhesus monkeys. AGMs appear to have a higher proportion of Env-specific memory B cells that are mainly gp120 directed. Furthermore, AGM gp120-specific monoclonal antibodies display robust antibody-dependent cellular cytotoxicity and CD4-dependent virion capture activity. Our results support the use of AGMs to model induction of functional gp120-specific antibodies by HIV vaccine strategies. PMID- 27381636 TI - Hepatitis C Virus Increases Free Fatty Acids Absorption and Promotes its Replication Via Down-Regulating GADD45alpha Expression. AB - BACKGROUND Hepatitis C virus (HCV) infection, as a major cause of chronic hepatic diseases, is always accompanied with an abnormality of lipid metabolism. The aim of this study was to investigate the pathogenic role of free fatty acids (FFA) in human HCV infection. MATERIAL AND METHODS Peripheral blood lipid indexes among HCV patients with different viral loads (199 samples) and healthy donors (80 samples) were detected by clinical biochemistry tests. HCV replication and the expression of growth arrest and DNA-damage-inducible gene 45-alpha (GADD45alpha) in Huh7 cells and clinical samples were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Lipid accumulation in Huh7 cells was detected by immunofluorescence. RESULTS In this study, we found that FFA showed a significant positive correlation with viral load in peripheral blood of HCV patients, but not total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C). GADD45alpha expression in HCV patients dramatically decreased with the increase of viral load. In Huh7 cells, FFA treatment significantly enhanced HCV replication. HCV infection inhibited GADD45alpha expression, and this effect was further enhanced with the presence of FFA treatment. Ectopic expression of GADD45alpha in HCV-infected Huh7 cells markedly inhibited the absorption of FFA and HCV replication. However, FFA significantly elevated GADD45alpha expression without HCV infection. CONCLUSIONS These results demonstrated that HCV down regulates GADD45alpha expression to enhance FFA absorption and thus facilitate its replication. GADD45alpha is an essential mediator for the pathogenesis of HCV infection. Thus, our study provides potential clues in the search for novel therapeutics and fatty lipid control options for HCV patients. PMID- 27381638 TI - NiCoMnO4: A Bifunctional Affinity Probe for His-Tagged Protein Purification and Phosphorylation Sites Recognition. AB - A bifunctional affinity probe NiCoMnO4 was designed and prepared with controllable morphology and size using facile methods. It was observed that the probe could be applied in His-tagged proteins purification and phosphopeptides enrichment simply through the buffer modulation. NiCoMnO4 particles showed satisfactory cycling performance for His-tagged proteins purification and broad pH-tolerance of loading buffer for phosphopeptides affinity. Therefore, a high throughput, cost-effective, and efficient protein/peptide purification method was developed within 10 min based on the novel bifunctional affinity probe. PMID- 27381635 TI - Maternal prenatal fish consumption and cognition in mid childhood: Mercury, fatty acids, and selenium. AB - BACKGROUND: Few studies of maternal prenatal fish intake have included biomarkers of exposure to mercury, long-chain n-3 fatty acids, and selenium, which are hypothesized to mediate associations with child neurodevelopment. OBJECTIVES: Examine associations of maternal prenatal fish intake with child neurodevelopment accounting for biomarkers. METHODS: In 1999-2002 we enrolled pregnant women into the Project Viva cohort. At median 27.9weeks gestation, we estimated maternal fish intake using food frequency questionnaires, and collected blood. We assayed erythrocytes for total mercury and selenium, and plasma for fatty acids including n-3 docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). In mid-childhood (median 7.7years), we administered cognitive tests including the Kauffman Brief Intelligence Test (KBIT). We performed multivariable linear regression analyses adjusting for maternal and child characteristics including home environment and maternal intelligence. RESULTS: Among 1068 pairs (872 with blood), mean (SD) exposures were: maternal fish intake 1.7 (1.5)servings/week, mercury 4.0 (3.6)ng/g, DHA+EPA 98.4 (41.8)mcg/ml, selenium 205.6 (34.6)ng/ml. Child KBIT verbal scores (mean 112.2, SD 15.0) were not related to any exposures: maternal fish intake (0.15; 95% CI: -0.50, 0.79), mercury (0.08; -0.18, 0.35), DHA+EPA (0.01; -0.22, 0.24), and selenium (0.20; -0.09, 0.50). Associations with KBIT nonverbal scores and tests of memory and visual motor abilities were similarly null. Mutual adjustment for each of the exposure measures did not substantially change estimates. CONCLUSIONS: In this population with an average fish consumption of about 1 1/2 weekly servings, we did not see any evidence for an association of maternal prenatal fish intake, or of mercury, DHA+EPA, or selenium status, with verbal or non-verbal intelligence, visual motor function, or visual memory at median 7.7years of age. PMID- 27381640 TI - Bringing critical realism to nursing practice: Roy Bhaskar's contribution. AB - In the context of modern nursing practice that is embedded within complex social situations, critical discussions about the contribution of major philosophers are relevant and important. Whilst nurse theorists have advanced and shaped nursing as a discipline, other major philosophers can offer much to advance nursing enquiry. In this paper, we focus on philosopher Roy Bhaskar who, amongst others, developed critical realism, a philosophy for social science which connects with how many of us think about the world. Bhaskar's work focuses our attention on the interplay between structure and agency and on the search for the causative or generative mechanisms that explain the social world. Bhaskar was interested in human emancipation, and we suggest his work is of great importance to advance understanding of complex social situations. Critical realism has already been endorsed by a range of disciplines, especially in research which focuses on real problems and acknowledges the complexities of the social world. In recent evidence from healthcare literature, there has been a surge in research using realist methodology (realist evaluation and realist synthesis), which is underpinned by the philosophy of critical realism and which offers a different perspective to understanding nursing and healthcare problems through the realist lens. However, we suggest that sufficient attention is not always paid to the philosophical roots of this methodology. In this paper, we provide insight into Bhaskar's work and demonstrate how research positioned within critical realism and realist methodology can advance nursing and healthcare-related knowledge. Through shining a light on Bhaskar, we illustrate how critical realism philosophy is a natural fit with human and health science enquiry, including nursing. PMID- 27381639 TI - Elevated Preoperative Serum Gamma-glutamyltranspeptidase Predicts Poor Prognosis for Hepatocellular Carcinoma after Liver Transplantation. AB - Gamma-glutamyltransferase (gamma-GGT) is a membrane-bound enzyme that is involved in biotransformation, nucleic acid metabolism, and tumourigenesis. Elevated serum gamma-GGT levels are related to an increased cancer risk and worse prognosis in many cancers. In the present study, we evaluated the prognostic value of preoperative serum gamma-GGT in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). A total of 130 HCC patients after LT were included in the study. The optimal cut-off value of gamma-GGT was 128U/L by receiver operating characteristic analysis, with a sensitivity and specificity of 60.0% and 72.9%, respectively. Elevated preoperative serum gamma-GGT was significantly associated with high alpha-fetoprotein (AFP), large tumor size, and macro- and micro-vascular invasion. The 1-, 3-, 5-year disease-free survival (DFS) and overall survival (OS) rates of HCC patients in the gamma-GGT > 128U/L group were poorer than those in the gamma-GGT <= 128U/L group. Stratification analysis revealed that gamma-GGT exhibited a greater predictive value for DFS and OS in HCC patients beyond the Milan criteria and no macro-vascular invasion. In conclusion, elevated preoperative serum gamma-GGT was significantly associated with advanced tumor stage and aggressive tumor behaviors, and serum gamma-GGT can be considered as a prognostic factor for HCC patients after LT, especially for patients beyond the Milan criteria or without macro-vascular invasion. PMID- 27381641 TI - Investigation of Localized States in GaAsSb Epilayers Grown by Molecular Beam Epitaxy. AB - We report the carrier dynamics in GaAsSb ternary alloy grown by molecular beam epitaxy through comprehensive spectroscopic characterization over a wide temperature range. A detailed analysis of the experimental data reveals a complex carrier relaxation process involving both localized and delocalized states. At low temperature, the localized degree shows linear relationship with the increase of Sb component. The existence of localized states is also confirmed by the temperature dependence of peak position and band width of the emission. At temperature higher than 60 K, emissions related to localized states are quenched while the band to band transition dominates the whole spectrum. This study indicates that the localized states are related to the Sb component in the GaAsSb alloy, while it leads to the poor crystal quality of the material, and the application of GaAsSb alloy would be limited by this deterioration. PMID- 27381642 TI - Immunogenicity and safety of inactivated quadrivalent influenza vaccine in adults: A systematic review and meta-analysis of randomised controlled trials. AB - BACKGROUND: A quadrivalent influenza vaccine (QIV) includes two A strains (A/H1N1, A/H3N2) and two B lineages (B/Victoria, B/Yamagata). The presence of both B lineages eliminate potential B lineage mismatch of trivalent influenza vaccine (TIV) with the circulating strain. METHODS: Electronic database searches of Medline, Embase, Cochrane Central Register of Controlled Trials (CCRCT), Scopus and Web of Science were conducted for articles published until June 30, 2015 inclusive. Articles were limited to randomised controlled trials (RCTs) in adults using inactivated intramuscular vaccine and published in English language only. Summary estimates of immunogenicity (by seroprotection and seroconversion rates) and adverse events outcomes were compared between QIV and TIV, using a risk ratio (RR). Studies were pooled using inverse variance weights with a random effect model and the I(2) statistic was used to estimate heterogeneity. RESULTS: A total of five RCTs were included in the meta-analysis. For immunogenicity outcomes, QIV had similar efficacy for the three common strains; A/H1N1, A/H3N2 and the B lineage included in the TIV. QIV also showed superior efficacy for the B lineage not included in the TIV; pooled seroprotection RR of 1.14 (95%CI: 1.03 1.25, p=0.008) and seroconversion RR of 1.78 (95%CI: 1.24-2.55, p=0.002) for B/Victoria, and pooled seroprotection RR of 1.12 (95%CI: 1.02-1.22, p=0.01) and seroconversion RR of 2.11 (95%CI: 1.51-2.95, p<0.001) for B/Yamagata, respectively. No significant differences were found between QIV and TIV for aggregated local and systemic adverse events within 7days post-vaccination. There were no vaccine-related serious adverse events reported for either QIV or TIV. Compared to TIV, injection-site pain was more common for QIV, with a pooled RR of 1.18 (95%CI: 1.03-1.35, p=0.02). CONCLUSION: In adults, inactivated QIV was as immunogenic as seasonal TIV, with equivalent efficacy against the shared three strains included in TIV, and a superior immunogenicity against the non-TIV B lineage. PMID- 27381644 TI - Catalytic enantioselective OFF <-> ON activation processes initiated by hydrogen transfer: concepts and challenges. AB - Hydrogen transfer initiated processes are eco-compatible transformations allowing the reversible OFF <-> ON activation of otherwise unreactive substrates. The minimization of stoichiometric waste as well as the unique activation modes provided by these transformations make them key players for a greener future for organic synthesis. Long limited to catalytic reactions that form racemic products, considerable progress on the development of strategies for controlling diastereo- and enantioselectivity has been made in the last decade. The aim of this review is to present the different strategies that enable enantioselective transformations of this type and to highlight how they can be used to construct key synthetic building blocks in fewer operations with less waste generation. PMID- 27381643 TI - Coordination as a best practice from the polio eradication initiative: Experiences from five member states in the African region of the World Health Organization. AB - BACKGROUND: As part of the efforts to eradicate polioviruses in the African Region, structures were put in place to ensure coordinated mobilization and deployment of resources within the framework of the global polio eradication initiative (PEI). The successes of these structures made them not only attractive to other public health interventions, but also caused them to be deployed to the response efforts of other diseases interventions, without any systematic documentation. This article documents the contributions of PEI coordination units to other public health interventions in the African Region of World Health Organization METHODS: We reviewed the contributions of PEI coordination units to other public health interventions in five countries in the African Region. RESULTS: The analysis identified significant involvement of PEI coordination structures in the implementation of routine immunization programs in all the countries analyzed. Similarly, maternal and child health programs were planned, implemented, monitored and evaluation the Inter-Agency Coordination Committees of the PEI programs in the different countries. The hubs system used in PEI in Chad facilitated the efficient coordination of resources for immunization and other public health interventions in Chad. Similarly, in the Democratic Republic of Congo PEI led coordination activities benefited other public health programs like disease control and the national nutrition program, the national malaria control program, and the tuberculosis control program. In Nigeria, the polio Expert Review Committee effectively deployed the Emergency Operation Center for the implementation of prioritized strategies and activities of the National Polio Eradication Emergency Plan, and it was utilized in the response to Ebola Virus Disease outbreak in the country. CONCLUSIONS: The PEI-led coordination systems are thus recognized as having made significant contribution to the coordination and delivery of other public health interventions in the African Region. PMID- 27381645 TI - Total Body Mass Estimation from Anthropometric Measurements in Modern Young Adult U.S. Populations with Healthy Body Fat Percentages (NHANES III). AB - This study presents a method by which to estimate total body mass in modern young adult U.S. populations who self-identified as non-Hispanic U.S. White, non Hispanic U.S. Black, and Mexican American with anthropometric measurements from the Third National Health and Nutrition Examination Survey (NHANES III) 1988-1994 dataset (N = 2532). Correlations of stature and bi-iliac breadth with total body mass were stronger among males (r = 0.717-0.774) than among females (r = 0.549 0.661), yet these results were more accurate assessments of total body mass than existing techniques. This study also examined additional anthropometric measurements to estimate total body mass using an information-theoretic approach demonstrating that some error in the stature-bi-iliac breadth method is attributed to a nonsupported model with multimodel inference. The limitations of the current total body mass technique are discussed as well as the need for future studies to validate the method. PMID- 27381647 TI - A Systematic Study of Structure and E-H Bond Activation Chemistry by Sterically Encumbered Germylene Complexes. AB - A series of new germylene compounds has been synthesized offering systematic variation in the sigma- and pi-capabilities of the alpha-substituent and differing levels of reactivity towards E-H bond activation (E=H, B, C, N, Si, Ge). Chloride metathesis utilizing [(terphenyl)GeCl] proves to be an effective synthetic route to complexes of the type [(terphenyl)Ge(ERn )] (1-6: ERn =NHDipp, CH(SiMe3 )2 , P(SiMe3 )2 , Si(SiMe3 )3 or B(NDippCH)2 ; terphenyl=C6 H3 Mes2 2,6=Ar(Mes) or C6 H3 Dipp2 -2,6=Ar(Dipp) ; Dipp=C6 H3 iPr2 -2,6, Mes=C6 H2 Me3 2,4,6), while the related complex [{(Me3 Si)2 N}Ge{B(NDippCH)2 }] (8) can be accessed by an amide/boryl exchange route. Metrical parameters have been probed by X-ray crystallography, and are consistent with widening angles at the metal centre as more bulky and/or more electropositive substituents are employed. Thus, the widest germylene units (theta>110 degrees ) are found to be associated with strongly sigma-donating boryl or silyl ancillary donors. HOMO-LUMO gaps for the new germylene complexes have been appraised by DFT calculations. The aryl(boryl) germylene system [Ar(Mes) Ge{B(NDippCH)2 }] (6-Mes), which features a wide C-Ge-B angle (110.4(1) degrees ) and (albeit relatively weak) ancillary pi-acceptor capabilities, has the smallest HOMO-LUMO gap (119 kJ mol(-1) ). These features result in 6-Mes being remarkably reactive, undergoing facile intramolecular C-H activation involving one of the mesityl ortho-methyl groups. The related aryl(silyl)-germylene system, [Ar(Mes) Ge{Si(SiMe3 )3 }] (5-Mes) has a marginally wider HOMO-LUMO gap (134 kJ mol(-1) ), rendering it less labile towards decomposition, yet reactive enough to oxidatively cleave H2 and NH3 to give the corresponding dihydride and (amido)hydride. Mixed aryl/alkyl, aryl/amido and aryl/phosphido complexes are unreactive, but amido/boryl complex 8 is competent for the activation of E-H bonds (E=H, B, Si) to give hydrido, boryl and silyl products. The results of these reactivity studies imply that the use of the very strongly sigma-donating boryl or silyl substituents is an effective strategy for rendering metallylene complexes competent for E-H bond activation. PMID- 27381646 TI - Inhibitory effect of 2-methyl-naphtho[1,2,3-de]quinolin-8-one on melanosome transport and skin pigmentation. AB - Melanosomes are lysosome-related organelles with specialized capabilities of melanin synthesis and movement mediated by the Rab27a-Melanophilin-MyosinVa protein complex. In this study, we found that 2-methyl-naphtho[1,2,3-de]quinolin 8-one (MNQO) induced melanosome aggregation around the nucleus in melan-a melanocytes and in melan-a melanocytes/SP-1 keratinocyte co-cultures without inducing toxicity or changing the melanin content. Western blot and real-time PCR analyses showed that MNQO decreased expression of the Rab27a, Melanophilin and MyosinVa proteins and mRNAs, respectively, in melan-a melanocytes. In a reconstituted human epidermis model, treatment with 0.001% MNQO reduced skin pigmentation. Also, MNQO reduced skin pigmentation in brown guinea pigs induced by UVB irradiation. These results indicated that regulation of melanosome transport may serve as a good target for new skin depigmenting agents and MNQO itself could be a candidate. PMID- 27381648 TI - Effects of systematic nursing instruction on a low-phosphorus diet, serum phosphorus level and pruritus of patients on haemodialysis. AB - AIMS AND OBJECTIVES: To investigate the effectiveness of systematic nursing instruction on a low-phosphorus diet, serum phosphorus level and pruritus of haemodialysis patients. BACKGROUND: A high number of end-stage renal disease patients on haemodialysis are bothered by pruritus. Hyperphosphataemia was reported to be related to pruritus. DESIGN: An experimental design was applied. METHODS: Ninety-four patients who received haemodialysis between September 2013 and December 2013 at a medical centre in Taipei, Taiwan, were recruited. An experimental group received individual systematic nursing instruction by the investigator through a nursing instruction pamphlet and reminder card for taking medication. A control group received traditional nursing instruction. The pruritus, blood phosphorus level and five-day diet records were evaluated before and after intervention. RESULTS: The experimental group had a low-phosphorus diet intake compared with the control group (p < 0.001). A significant difference in serum phosphorus level was observed between the experimental and control groups (p = 0.002). Incidence of pruritus was lower in the experimental group than in the control group (p < 0.001). CONCLUSION: A systematic nursing instruction included using a pamphlet, pictures and reminder cards, the patients' blood phosphorus levels decreased, the patients consumed more low-phosphorus food, and pruritus decreased. RELEVANCE TO CLINICAL PRACTICE: This study recommends that clinical nursing staff include systematic nursing instruction as a routine practice for dialysis patients. PMID- 27381649 TI - Selective MS screening reveals a sex pheromone in Caenorhabditis briggsae and species-specificity in indole ascaroside signalling. AB - The indole ascarosides (icas) represent a highly potent class of nematode-derived modular signalling components that integrate structural inputs from amino acid, carbohydrate, and fatty acid metabolism. Comparative analysis of the crude exo metabolome of hermaphroditic Caenorhabditis briggsae using a highly sensitive mass spectrometric screen reveals an indole ascaroside blend dominated by two new components. The structures of isolated icas#2 and icas#6.2 were determined by NMR spectroscopy and confirmed by total synthesis and chemical correlation. Low atto- to femtomolar amounts of icas#2 and icas#6.2 act in synergism to attract males indicating a function as sex pheromone. Comparative analysis of 14 Caenorhabditis species further demonstrates that species-specific indole ascaroside biosynthesis is highly conserved in the Elegans group. Functional characterization of the dominating indole ascarosides icas#2, icas#3, and icas#9 reveals a high degree of species-specificity and considerable variability with respect to gender specificity, thus, confirming that indole ascarosides modulate different biological functions within the Elegans group. Although the nematode response was usually most pronounced towards conspecific signals, Caenorhabditis brenneri, the only species of the Elegans group that does not produce any indole ascarosides, exhibits a robust response to icas#2 suggesting the potential for interspecies interactions. PMID- 27381651 TI - High-Quality Crystal Growth and Characteristics of AlGaN-Based Solar-Blind Distributed Bragg Reflectors with a Tri-layer Period Structure. AB - To realize AlGaN-based solar-blind ultraviolet distributed Bragg reflectors (DBRs), a novel tri-layer AlGaN/AlInN/AlInGaN periodical structure that differs from the traditional periodically alternating layers of high- and low-refractive index materials was proposed and grown on an Al0.5Ga0.5N template via metal organic chemical vapour deposition. Because of the intentional design of the AlInGaN strain transition layer, a state-of-the-art DBR structure with atomic level-flatness interfaces was achieved using an AlGaN template. The fabricated DBR exhibits a peak reflectivity of 86% at the centre wavelength of 274 nm and a stopband with a full-width at half-maximum of 16 nm. PMID- 27381650 TI - The BB2 receptor antagonist BW2258U89 attenuates the feeding responses evoked by exogenous gastrin releasing peptide-29. AB - This confirmatory work is aimed to test that the hypothesis that the gastrin releasing peptide (GRP) receptor - the BB2 receptor - is necessary for reduction of meal size (MS) and prolongation of the intermeal interval (IMI) by the small and the large forms of GRP in the rat, GRP-10 and GRP-29, and to confirm the sites of action regulating such responses - the vascular bed of the celiac artery (CA, supplying stomach and upper duodenum). To pursue these aims we measured first MS and IMI length in response to GRP-10 and GRP-29 (0, 0.5nmol/kg) infused in the CA (n=8 rats) and the cranial mesenteric artery (CMA, supplying the small and part of the large intestine, n=8 rats) in near spontaneously free feeding rats pretreated with the BB2 receptor antagonist BW2258U89 (0.1mg/kg) in the same arteries prior to the onset of the dark cycle. We found that GRP-29, but not GRP 10, infused by the CA reduced MS and prolonged the IMI by decreasing meal latency and meal duration and the BB2 receptor antagonist BW2258U89 infused in the same artery attenuated these responses. These results suggest that the BB2 receptor is necessary for reduction of MS and prolongation of the IMI by exogenous GRP-29, and the vascular bed of the CA, stomach and upper duodenum, contains sites of action regulating these feeding responses. PMID- 27381652 TI - Reduced-intensity or myeloablative allogeneic hematopoietic cell transplantation for mantle cell lymphoma: a systematic review. AB - Allogeneic hematopoietic cell transplantation (allo-HCT) is the only known treatment that can offer a cure in mantle cell lymphoma, but it is unclear if regimen dose-intensity offers any advantage. We performed a systematic review/meta-analysis to assess efficacy of allo-HCT using myeloablative or reduced-intensity conditioning. We report results according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. On the basis of a relatively lower nonrelapse mortality and a slightly better progression-free survival/event-free survival and overall survival rates, reduced-intensity allo HCT regimens appear to be the preferred choice when an allo-HCT is being considered for mantle cell lymphoma. The higher rate of relapse when offering reduced-intensity regimens cannot be ignored but certainly highlights opportunities to incorporate post-transplant strategies to mitigate this risk. A prospective comparative study is ultimately needed to generate more conclusive evidence. PMID- 27381653 TI - Fractures of the tibial plateau involve similar energies as the tibial pilon but greater articular surface involvement. AB - Patients with tibial pilon fractures have a higher incidence of post-traumatic osteoarthritis than those with fractures of the tibial plateau. This may indicate that pilon fractures present a greater mechanical insult to the joint than do plateau fractures. We tested the hypothesis that fracture energy and articular fracture edge length, two independent indicators of severity, are higher in pilon than plateau fractures. We also evaluated whether clinical fracture classification systems accurately reflect severity. Seventy-five tibial plateau fractures and 52 tibial pilon fractures from a multi-institutional study were selected to span the spectrum of severity. Fracture severity measures were calculated using objective CT-based image analysis methods. The ranges of fracture energies measured for tibial plateau and pilon fractures were 3.2-33.2 Joules (J) and 3.6-32.2 J, respectively, and articular fracture edge lengths were 68.0-493.0 mm and 56.1-288.6 mm, respectively. There were no differences in the fracture energies between the two fracture types, but plateau fractures had greater articular fracture edge lengths (p < 0.001). The clinical fracture classifications generally reflected severity, but there was substantial overlap of fracture severity measures between different classes. Similar fracture energies with different degrees of articular surface involvement suggest a possible explanation for dissimilar rates of post-traumatic osteoarthritis for fractures of the tibial plateau compared to the tibial pilon. The substantial overlap of severity measures between different fracture classes may well have confounded prior clinical studies relying on fracture classification as a surrogate for severity. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:618-624, 2017. PMID- 27381654 TI - Proteomics reveals reduced expression of transketolase in pyrimidine 5' nucleotidase deficient patients. AB - PURPOSE: To date, it remains a challenge to correctly and timely diagnose red blood cell (RBC) enzymopathies that result in hereditary nonspherocytic hemolytic anemia (HNSHA), the third most common of which is pyrimidine 5'-nucleotidase (P5N) deficiency with just over 100 cases recognized and confirmed worldwide. EXPERIMENTAL DESIGN: We have investigated the RBC proteome of a patient with P5N deficiency due to a homozygous frameshift mutation in the NT5C3A gene. Protein expression levels were analyzed against healthy controls and against patients with hemolytic anemia of different origin, to account for the patient's elevated reticulocyte versus RBC ratio. RESULTS: Stringent relative quantification of the patient's protein levels revealed reduced levels of P5N, and unexpectedly, also decreased levels of transketolase, an enzyme involved in the nonoxidative phase of the pentose phosphate pathway, one of the few key pathways active in RBCs. Immunoblotting of whole blood samples from this and other P5N-deficient patients with dissimilar mutations indicated that P5N deficiency was correlated with reduced transketolase levels. CONCLUSIONS AND CLINICAL RELEVANCE: Consequently, insight into patient RBC proteomes illustrates potential benefit of coupling quantitative proteomics strategies with routine HNSHA diagnostic procedures. Proteomics facilitates finding novel biomarkers for HNSHA patients, for example, suffering from P5N deficiency, providing new prospects for future diagnosis and therapy. PMID- 27381655 TI - Megalencephaly, polymicrogyria and ribbon-like band heterotopia: A new cortical malformation. AB - Megalencephalic polymicrogyria syndromes include megalencephaly-capillary malformation and megalencephaly-polymicrogyria-polydactyly-hydrocephalus. Recent genetic studies have identified that genes in the PI3K-AKT pathway are involved in the pathogenesis of these disorders. Herein, we report a patient who presented with developmental delay, epilepsy and peculiar neuroimaging findings of megalencephaly, polymicrogyria, and symmetrical band heterotopia in the periventricular region. The heterotopias exhibited inhomogeneous signals with undulatory mixtures of gray and white matter, resembling ribbon-like heterotopia, with a predominance in the temporal to occipital regions. These neuroradiological findings were not consistent with those in known megalencephalic polymicrogyria syndromes. No genetic abnormality was identified through whole-exome sequencing. The neuroimaging findings of this patient may represent a novel cortical malformation involving megalencephaly with polymicrogyria and ribbon-like band heterotopia. PMID- 27381656 TI - Molecular and cellular mechanisms underlying the therapeutic effects of budesonide in asthma. AB - Inhaled glucocorticoids are the mainstay of asthma treatment. Indeed, such therapeutic agents effectively interfere with many pathogenic circuits underpinning asthma. Among these drugs, during the last decades budesonide has been probably the most used molecule in both experimental studies and clinical practice. Therefore, a large body of evidence clearly shows that budesonide, either alone or in combination with long-acting bronchodilators, provides a successful control of asthma in many patients ranging throughout the overall spectrum of disease severity. These excellent therapeutic properties of budesonide basically depend on its molecular mechanisms of action, capable of inhibiting within the airways the activity of multiple immune-inflammatory and structural cells involved in asthma pathobiology. PMID- 27381657 TI - Gender-related impact on outcomes of high density lipoprotein in acute ST elevation myocardial infarction. AB - BACKGROUND AND AIMS: There is rising evidence that cardioprotective functions of high-density lipoprotein (HDL) have significant impact on clinical outcomes. ST elevation myocardial infarction (STEMI) represents a high-risk vascular condition. Whether higher HDL-cholesterol concentrations in women correspond to protective anti-oxidant properties in the setting of STEMI is unknown. METHODS: We prospectively assessed gender related differences in the anti-oxidant function of HDL, and the impact of HDL properties on mortality in 242 women and men with STEMI. Blood samples to determine HDL function and sex hormone levels were collected during primary percutaneous coronary intervention. RESULTS: Patients were stratified according to preserved anti-oxidant HDL function (HDL oxidant index (HOI) < 1) and pro-oxidant HDL (HOI>=1). Despite higher serum levels of HDL cholesterol in postmenopausal women (48 mg/dl, IQR 42-54, versus 39 mg/dl, IQR33 47, p < 0.001 in men), the proportion of patients with pro-oxidant HDL was not different between women (35%) and men (46%, p = 0.132). Kaplan-Meier analysis revealed higher cardiovascular mortality in both women (p = 0.021) and men (p = 0.045) with pro-oxidant HDL. We identified pro-oxidant HDL as strong and independent predictor of cardiovascular mortality with an adjusted HR of 8.33 (95% CI, 1.55-44.63; p = 0.013) in women and with an adjusted HR of 5.14 (95% CI, 1.61-16.42; p = 0.006) in men. Higher levels of free sex hormones (estradiol and testosterone) were associated with pro-oxidant HDL. HDL-cholesterol levels showed no association with mortality (HR in women 1.03, 95% CI 0.96-1.11, p = 0.45 and HR in men 0.99, 95% CI 0.94-1.05, p = 0.72). CONCLUSIONS: Total HDL-cholesterol serum levels were not associated with mortality in STEMI patients. Pro-oxidant HDL was a strong and independent predictor of mortality in women and men with STEMI. The present study provides a link between sex hormones, HDL function and clinical events in STEMI patients. In clinical practice and future clinical trials, anti-oxidant properties of HDL rather than total HDL serum levels should be used for risk stratification. PMID- 27381659 TI - Editorial. PMID- 27381658 TI - Single cell dual adherent-suspension co-culture micro-environment for studying tumor-stromal interactions with functionally selected cancer stem-like cells. AB - Considerable evidence suggests that cancer stem-like cells (CSCs) are critical in tumor pathogenesis, but their rarity and transience has led to much controversy about their exact nature. Although CSCs can be functionally identified using dish based tumorsphere assays, it is difficult to handle and monitor single cells in dish-based approaches; single cell-based microfluidic approaches offer better control and reliable single cell derived sphere formation. However, like normal stem cells, CSCs are heavily regulated by their microenvironment, requiring tumor stromal interactions for tumorigenic and proliferative behaviors. To enable single cell derived tumorsphere formation within a stromal microenvironment, we present a dual adherent/suspension co-culture device, which combines a suspension environment for single-cell tumorsphere assays and an adherent environment for co culturing stromal cells in close proximity by selectively patterning polyHEMA in indented microwells. By minimizing dead volume and improving cell capture efficiency, the presented platform allows for the use of small numbers of cells (<100 cells). As a proof of concept, we co-cultured single T47D (breast cancer) cells and primary cancer associated fibroblasts (CAF) on-chip for 14 days to monitor sphere formation and growth. Compared to mono-culture, co-cultured T47D have higher tumorigenic potential (sphere formation rate) and proliferation rates (larger sphere size). Furthermore, 96-multiplexed single-cell transcriptome analyses were performed to compare the gene expression of co-cultured and mono cultured T47D cells. Phenotypic changes observed in co-culture correlated with expression changes in genes associated with proliferation, apoptotic suppression, tumorigenicity and even epithelial-to-mesechymal transition. Combining the presented platform with single cell transcriptome analysis, we successfully identified functional CSCs and investigated the phenotypic and transcriptome effects induced by tumor-stromal interactions. PMID- 27381660 TI - Different reactivity of primary fibroblasts and endothelial cells towards crystalline silica: A surface radical matter. AB - Quartz is a well-known occupational fibrogenic agent able to cause fibrosis and other severe pulmonary diseases such as silicosis and lung cancer. The silicotic pathology owes its severity to the structural and chemo-physical properties of the particles such as shape, size and abundance of surface radicals. In earlier studies, we reported that significant amounts of surface radicals can be generated on crystalline silica by chemical aggression with ascorbic acid (AA), a vitamin naturally abundant in the lung surfactant, and this reaction led to enhanced cytotoxicity and production of inflammatory mediators in a macrophage cell line. However in the lung, other cells acting in the development of silicosis, like fibroblasts and endothelial cells, can come to direct contact with inhaled quartz. We investigated the cytotoxic/pro-inflammatory effects of AA treated quartz microcrystals (QA) in human primary fibroblasts and endothelial cells as compared to unmodified microcrystals (Q). Our results show that, in fibroblasts, the abundance of surface radicals on quartz microcrystals (Q vs QA) significantly enhanced cell proliferation (with or without co-culture with macrophages), reactive oxygen species (ROS) production, NF-kappaB nuclear translocation, smooth muscle actin, fibronectin, Bcl-2 and tissue inhibitor of metalloproteinase-1 expression and collagen production. Contrariwise, endothelial cells reacted to the presence of quartz microcrystals independently from the abundance of surface radicals showing similar levels of cytotoxicity, ROS production, cell migration, MCP-1, ICAM-I and fibronectin gene expression when challenged with Q or QA. In conclusion, our in vitro experimental model demonstrates an important and quite unexplored direct contribute of silica surface radicals to fibroblast proliferation and fibrogenic responses. PMID- 27381662 TI - Coordination-Cluster-Based Molecular Magnetic Refrigerants. AB - Coordination polymers serving as molecular magnetic refrigerants have been attracting great interest. In particular, coordination cluster compounds that demonstrate their apparent advantages on cryogenic magnetic refrigerants have attracted more attention in the last five years. Herein, we mainly focus on depicting aspects of syntheses, structures, and magnetothermal properties of coordination clusters that serve as magnetic refrigerants on account of the magnetocaloric effect. The documented molecular magnetic refrigerants are classified into two primary categories according to the types of metal centers, namely, homo- and heterometallic clusters. Every section is further divided into several subgroups based on the metal nuclearity and their dimensionalities, including discrete molecular clusters and those with extended structures constructed from molecular clusters. The objective is to present a rough overview of recent progress in coordination-cluster-based molecular magnetic refrigerants and provide a tutorial for researchers who are interested in the field. PMID- 27381661 TI - Enhancement of Low-field Magnetoresistance in Self-Assembled Epitaxial La0.67Ca0.33MnO3:NiO and La0.67Ca0.33MnO3:Co3O4 Composite Films via Polymer Assisted Deposition. AB - Polymer-assisted deposition method has been used to fabricate self-assembled epitaxial La0.67Ca0.33MnO3:NiO and La0.67Ca0.33MnO3:Co3O4 films on LaAlO3 substrates. Compared to pulsed-laser deposition method, polymer-assisted deposition provides a simpler and lower-cost approach to self-assembled composite films with enhanced low-field magnetoresistance effect. After the addition of NiO or Co3O4, triangular NiO and tetrahedral Co3O4 nanoparticles remain on the surface of La0.67Ca0.33MnO3 films. This results in a dramatic increase in resistivity of the films from 0.0061 Omega*cm to 0.59 Omega*cm and 1.07 Omega*cm, and a decrease in metal-insulator transition temperature from 270 K to 180 K and 172 K by the addition of 10%-NiO and 10%-Co3O4, respectively. Accordingly, the maximum absolute magnetoresistance value is improved from -44.6% to -59.1% and 52.7% by the addition of 10%-NiO and 10%-Co3O4, respectively. The enhanced low field magnetoresistance property is ascribed to the introduced insulating phase at the grain boundaries. The magnetism is found to be more suppressed for the La0.67Ca0.33MnO3:Co3O4 composite films than the La0.67Ca0.33MnO3:NiO films, which can be attributed to the antiferromagnetic properties of the Co3O4 phase. The solution-processed composite films show enhanced low-field magnetoresistance effect which are crucial in practical applications. We expect our polymer assisted deposited films paving the pathway in the field of hole-doped perovskites with their intrinsic colossal magnetoresistance. PMID- 27381663 TI - Airway remodelling in COPD: It's not asthma! AB - COPD is defined as airflow limitation that is not reversed by treatment. In asthma, airflow limitation is not only reversible, but also inducible. This is called 'airway hyperresponsiveness' (AHR) and is associated with thickening of the airway wall, predominantly the layer of airway smooth muscle, due to more cells, bigger cells and more extracellular matrix (ECM) in proportion to the increase in smooth muscle. AHR is also observed in COPD if the changes in airflow are expressed as a percent of the baseline lung function. However, the absolute change in baseline lung function that can be induced in COPD is actually less than that seen in normal subjects, suggesting that the airways in COPD are resistant not only to opening, but also to closing. This observation agrees with physiological measures showing increased airway wall stiffness in COPD. Like asthma, airway wall thickness is increased in COPD, including the layer of smooth muscle. Unlike asthma, however, fixed airflow obstruction appears to be characterized by a disproportionate increase in the ECM within the smooth muscle layer. In this review, we summarize the studies of airway matrix deposition in COPD and put forward the proposal that the airway remodelling in COPD is different from that in asthma and call for a systematic analysis of airway matrix deposition in COPD. PMID- 27381664 TI - Relation of Obesity to Survival After In-Hospital Cardiac Arrest. AB - Previous studies have shown that obesity is paradoxically associated with improved outcomes in many cardiovascular (CV) disease states; however, whether obesity affects survival after in-hospital cardiac arrest (IHCA) has not been well examined. We queried the 2003 to 2011 Nationwide Inpatient Sample databases to identify all patients aged >=18 years who underwent cardiopulmonary resuscitation for IHCA. Obese patients were identified using the co-morbidity variable for obesity, as defined in Nationwide Inpatient Sample databases. Survival to hospital discharge was compared between obese and nonobese patients using multivariate regression models. Of 836,289 patients with IHCA, 67,216 (8.0%) were obese. Obese patients were younger and more likely to be women compared with nonobese patients. Despite being younger, obese patients had significantly higher prevalence of most CV co-morbidities such as dyslipidemia, coronary artery disease, previous myocardial infarction, heart failure, diabetes mellitus, hypertension, peripheral vascular disease, and chronic renal failure (p <0.001 for all). Obese patients were more likely to have ventricular tachycardia or ventricular fibrillation as the initial cardiac arrest rhythm (22.3% vs 20.9%; p <0.001). After multivariate risk adjustment, obese patients had improved survival to hospital discharge compared with nonobese patients (31.4% vs 24.1%; unadjusted odds ratio 1.44, 95% CI 1.42 to 1.47, p <0.001; adjusted odds ratio 1.15, 95% CI 1.13 to 1.17, p <0.001). Similar results were seen in patients with CV or non-CV conditions as the primary diagnosis and in those with ventricular tachycardia/ventricular fibrillation or pulseless electrical activity/asystole as the cardiac arrest rhythm. In conclusion, this large retrospective analysis of a nationwide cohort of patients with IHCA demonstrated higher risk-adjusted odds of survival in obese patients, consistent with an "obesity paradox." PMID- 27381666 TI - Dizziness Playing the Saxophone Secondary to Hypertrophic Cardiomyopathy. AB - A decrease in left ventricular volume increases the severity of left ventricular outflow tract obstruction in patients with obstructive hypertrophic cardiomyopathy, formerly called idiopathic hypertrophic subaortic stenosis. Because of this, a musician with the condition develops dizziness playing his saxophone which requires repeated and prolonged Valsalva maneuvers. PMID- 27381665 TI - Transcatheter Aortic Valve Replacement Versus Surgery in Women at High Risk for Surgical Aortic Valve Replacement (from the CoreValve US High Risk Pivotal Trial). AB - The objective of this study was to compare outcomes in women after surgical aortic valve replacement (SAVR) versus transcatheter aortic valve replacement (TAVR) using a self-expanding prosthesis in patients with severe aortic stenosis who were at high risk for SAVR. Although registries and meta-analyses have suggested that TAVR is of considerable benefit in women, perhaps even more so than in men, a rigorous evaluation of TAVR with a self-expanding valve versus SAVR in women from a randomized trial has not been performed. Patients with severe aortic stenosis were randomized 1:1 to either TAVR or SAVR. Outcomes at 1 year are reported. Treatment was attempted in a total of 353 women (183 TAVR and 170 SAVR). Baseline characteristics and predicted risk of the 2 groups were comparable, although the frequency of diabetes mellitus was lower in patients undergoing TAVR (33.3% vs 45.3%; p = 0.02). TAVR-treated patients experienced a statistically significant 1-year survival advantage compared with SAVR patients (12.7% vs 21.8%; p = 0.03). The composite all-cause mortality or major stroke rate also favored TAVR (14.9% vs 24.2%; p = 0.04). Quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire summary score, for both the TAVR and SAVR groups increased significantly from baseline to 1 year. In conclusion, female TAVR patients had lower 1-year mortality and lower 1-year all-cause mortality or major stroke compared with women undergoing SAVR, with both cohorts experiencing improved quality of life. Further studies specifically in women are warranted to validate these findings. PMID- 27381667 TI - Electrocardiographic Abnormalities in Disease-Free Black South Africans and Correlations With Echocardiographic Indexes and Early Repolarization. AB - Electrocardiographic abnormalities, and specifically early repolarization (ER) patterns, are increasingly found to be common variants in healthy populations free of heart disease or risk factors. Data are sparse in subjects of African descent, for which no increase in adverse cardiovascular outcomes have been demonstrated. A database of healthy disease-free adult volunteers of sub-Saharan African descent had 12 lead electrocardiograms (ECGs) and transthoracic echocardiograms performed. Statistical tests were then performed on the data to elicit associations; 396 volunteers (63.1% women) with a mean age of 37.4 years met the inclusion and exclusion criteria. An abnormal ECG was identified in 50.5% of volunteers, largely because of underlying ST elevation at the J point (ER), left ventricular hypertrophy (LVH) by voltage criteria, and T-wave inversion. Men were more likely to have abnormal ECGs (odds ratio [OR] 1.75; p <0.001), axes (OR 2.05; p = 0.023), display LVH by Sokolow-Lyon voltage criteria (OR 5.45; p <0.001), and have ER patterns (OR 11.61; p <0.001). Additionally, younger adults were also more likely to display LVH by voltage criteria and ER patterns. Volunteers with LVH by ECG had 5.7% higher LV mass indexes (p = 0.047). An abnormal ECG was not associated with a reduced left ventricular ejection fraction or diastolic dysfunction. ECG abnormalities, especially ER patterns, in black adults of Sub-Saharan descent are common, occurring in half of the normal adults. PMID- 27381668 TI - Comparison of Inhospital Mortality and Frequency of Coronary Angiography on Weekend Versus Weekday Admissions in Patients With Non-ST-Segment Elevation Acute Myocardial Infarction. AB - Patients with myocardial infarction admitted on weekends have been reported to less frequently undergo invasive angiography and experience poorer outcomes. We used the Nationwide Inpatient Sample database (2003 to 2011) to compare differences in all-cause inhospital mortality between patients admitted on a weekend versus weekday for an acute non-ST-segment elevation myocardial infarction (NSTEMI) and to determine if rates and timing of coronary revascularization contributed to this difference. A total of 3,625,271 NSTEMI admissions were identified, of which 909,103 (25.1%) were weekend and 2,716,168 (74.9%) were weekday admissions. Admission on a weekend versus weekday was independently associated with lower rates of coronary angiography (odds ratio [OR] 0.88; 95% confidence interval [CI] 0.89 to 0.90; p <0.001) or utilization of an early invasive strategy (EIS) (OR 0.480; 95% CI 0.47 to 0.48; p <0.001). Unadjusted inhospital mortality was significantly higher for the cohort of patients admitted on weekends (adjusted OR 1.02; 95% CI 1.01 to 1.04; p <0.001). However, this disparity was no longer significant after adjustment for differences in rates of utilization of EIS (OR 1.01; 95% CI 0.99 to 1.03; p = 0.11). In conclusion, this study demonstrates that among patients admitted with a diagnosis of an acute NSTEMI, admission on a weekend was associated with higher inhospital mortality compared with admission on a weekday and that lower rates of utilization of EIS contributed significantly to this disparity. PMID- 27381669 TI - Reliability of the Size Evaluation Method for Meningiomas: Maximum Diameter, ABC/2 Formula, and Planimetry Method. AB - BACKGROUND: To evaluate the accuracy of tumor size by maximum diameter, ABC/2 formula, and planimetry method using thick-slice and thin-slice magnetic resonance imaging (MRI). METHODS: Maximum diameter and tumor volume calculated using ABC/2 formula (V1) and planimetry method with thick-slice MRI (V2) and thin slice MRI (V3) were examined in 83 meningiomas. Form factor (FF) analysis was performed to assess irregularity of the tumor. V3 values were considered as real tumor volumes. The accuracy of V1 and V2 was evaluated using ratio and difference from V3. Meningiomas were categorized by tumor locations: skull base (anterior, middle, and posterior) and non-skull base (calvaria and other sites). RESULTS: Correlation between maximum diameter and V3 was statistically significant (r = 0.91), but the error was significant in tumors with longer maximum diameters. Correlation between V1 and V3 was significant (r = 0.97). However, V1 tended to be larger in middle skull base meningiomas or in tumors with low FF values (R2 = 0.21). V2 represented relatively accurate volumes in both groups except in the case of small meningiomas. When tumors were demonstrated within 3 fractions on thick-slice MRI, the ratio of V2 to V3 showed significant variability. CONCLUSIONS: Using the ABC/2 formula, the volume of meningiomas in the middle skull base or meningiomas with low FF value might be calculated larger than the real tumor volume. The planimetry method with thick-slice MRI demonstrated relatively accurate volumes if the tumor was fractionated in >4 slices. PMID- 27381670 TI - Role of agonistic autoantibodies against type-1 angiotensin II receptor in the pathogenesis of retinopathy in preeclampsia. AB - To investigate the mechanism underlying AT1-AA-induced retinopathy in severe preeclampsia by measuring the positive rate and titer of AT1-AA in plasma from women with severe preeclampsia and normal pregnant women to see whether AT1-AA titer was correlated with the grade of retinopathy. A preeclampsia rat model was also established by intravenous injection of AT1-AA extracted from the plasma of patient suffering from severe preeclampsia. The results showed that the plasma titer and positive rate of AT1-AA were significantly higher in women with severe preeclampsia than normal pregnant women. The antibody titer in cases of severe preeclampsia was associated with the grade of retinopathy, and positively correlated with the level of TNF-alpha and VEGF. The animal experiment results showed that the modeled rats presented symptoms very similar to symptoms of human preeclampsia, including retinopathy. Ocular fundus examination showed retinal microvascular abnormalities, hemorrhaging and leakage in the severe preeclampsia. Morphological changes included edema, thickening of the INL and ONL, and pigment atrophy. TNF-alpha and VEGF levels were increased in the vitreous humor and retina of the model rats. Our studies results suggest that abnormal expression of AT1-AA could induce damage to retinal capillary endothelial cells and increase vascular permeability, resulting in retinopathy. PMID- 27381671 TI - Potent in vitro antiproliferative properties for a triplatinum cluster toward triple negative breast cancer cells. AB - The trinuclear platinum cluster [Pt3(MU-PBut2)3(CO)3]CF3SO3 (I) was designed featuring the presence of a nearly equilateral platinum triangle bridged by three di-tert-butylphosphide ligands; in addition, each platinum center bears a terminal carbonyl ligand. This triplatinum cluster was initially developed in view of applications in the field of cluster-containing innovative materials. Yet, due to the large success of platinum complexes in cancer treatment, we also decided to explore its cytotoxic and anticancer properties. Accordingly, the solubility profile of this compound in several solvents was preliminarily investigated, revealing a conspicuous solubility in DMSO and DMSO/buffer mixtures; this makes the biological testing of I amenable. UV-Vis measurements showed that the triplatinum cluster is stable for several hours under a variety of conditions, within aqueous environments. No measurable reactivity was observed for I toward two typical model proteins, i.e. lysozyme and cytochrome c. On the contrary, a significant reactivity was evidenced when reacting I with small sulfur-containing ligands. In particular, a pronounced reactivity with reduced glutathione and cysteine emerged from ESI-MS experiments, proving complete formation of I-GSH and I-Cys derivatives, with the loss of a single carbonyl ligand. Starting from these encouraging results, the cytotoxic potential of I was assayed in vitro against a panel of representative cancer cell lines, and potent cytotoxic properties were disclosed. Of particular interest is the finding that the triplatinum species manifests potent antiproliferative properties toward Triple Negative Breast Cancer Cells, often refractory to most anticancer drugs. Owing to the reported encouraging results, a more extensive biological and pharmacological evaluation of this Pt cluster is now warranted to better elucidate its mode of action. PMID- 27381672 TI - Left main coronary artery occlusion in an asymptomatic patient: late complication after arterial switch operation. AB - Long-term complications of the arterial switch operation for transposition of the great arteries include coronary artery stenosis and occlusion. We present a patient with high-grade left main coronary artery stenosis 18 years following the arterial switch procedure who was successfully treated with a left internal mammary artery to left anterior descending artery bypass. PMID- 27381674 TI - Transplantation after ex vivo lung perfusion: A midterm follow-up. AB - BACKGROUND: A large proportion of donor lungs are discarded due to known or presumed organ dysfunction. Ex vivo lung perfusion (EVLP) has proven its value as a tool for discrimination between reversible and irreversible donor lung pathology. However, the long-term outcome after transplantation of lungs after EVLP is essentially unknown. We report short-term and midterm outcomes of recipients who received transplants of EVLP-evaluated lungs. METHODS: Single center results of recipients of lungs with prior EVLP were compared with consecutive recipients of non-EVLP lungs (controls) during the same period. Short term follow-up included time to extubation, time in the intensive care unit, and the presence of primary graft dysfunction at 72 hours postoperatively. Mortality and incidence of chronic lung allograft dysfunction were monitored for up to 4 years after discharge. RESULTS: During a 4-year period, 32 pairs of initially rejected donor lungs underwent EVLP. After EVLP, 22 double lungs and 5 single lungs were subsequently transplanted. During this period, 145 patients received transplants of conventional donor lungs that did not have EVLP and constituted the control group. Median time to extubation was 7 hours in the EVLP group and 6 hours in the non-EVLP control group (p = 0.45). Median intensive care unit stay was 4 days vs. 3 days, respectively (p = 0.15). Primary graft dysfunction grade > 1 was present in 14% in the EVLP group and in 12% in the non-EVLP group at 72 hours after transplant. Survival at 1 year was 92% in the EVLP group and 79% in the non-EVLP group. Cumulative survival and freedom from retransplantation or chronic rejection were also comparable between the 2 groups (p = 0.43) when monitored up to 4 years. CONCLUSIONS: Selected donor lungs rejected for transplantation can be used after EVLP. This technique is effective for selection of transplantable donor lungs. Patients who received lungs evaluated under EVLP have short-term and midterm outcomes comparable to recipients of non-EVLP donor lungs. PMID- 27381675 TI - Lung transplantation following coronary artery bypass surgery-improved outcomes following single-lung transplant. AB - BACKGROUND: Prior coronary artery bypass grafting (CABG) has been a contraindication to lung transplantation (LTx) because of disease severity and technical considerations. Although patients increasingly are being referred for and receiving LTx, whether it should remain a contraindication is unknown. We sought to define the prevalence of LTx after CABG and determine the effect on outcomes. METHODS: The United Network for Organ Sharing Standard Transplant Analysis and Research data set was queried during the period 2004-2013 for adult LTx patients, as prior CABG became a mandatory reporting field in 2004. The primary end-points were 30-day and 1-, 3-, and 5-year survivals. RESULTS: The study cohort included 14,791 patients, of whom 292 patients had previously undergone CABG (single left, n = 68; single right, n = 181; bilateral, n = 43), representing 2% of all transplants. For the entire cohort, 30-day survival was 97%, and survival at 1, 3, and 5 years was 88%, 79%, and 74%. CABG was a predictor of mortality at all time points, with hazard ratios ranging from 1.97 (confidence interval, 1.23-3.16; p < 0.01) at 30 days to 1.38 (confidence interval, 1.12-1.69; p < 0.01) at 5 years. When stratified by type of transplant, CABG strongly predicted mortality at all time points for patients receiving bilateral, but not single, transplants. CONCLUSIONS: Although LTx after CABG is uncommon, it is increasingly performed in the current era. Single right LTx is the most common procedure performed in patients with prior CABG. CABG before LTx is an independent predictor of mortality at all time points and is driven by increased mortality in patients receiving bilateral LTx. PMID- 27381673 TI - Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus. AB - Advanced management of dysmetabolic syndromes such as diabetes will benefit from a timely mechanistic insight enabling personalized medicine approaches. Herein, we present a rapid microfluidic neutrophil sorting and functional phenotyping strategy for type 2 diabetes mellitus (T2DM) patients using small blood volumes (fingerprick ~100 MUL). The developed inertial microfluidics technology enables single-step neutrophil isolation (>90% purity) without immuno-labeling and sorted neutrophils are used to characterize their rolling behavior on E-selectin, a critical step in leukocyte recruitment during inflammation. The integrated microfluidics testing methodology facilitates high throughput single-cell quantification of neutrophil rolling to detect subtle differences in speed distribution. Higher rolling speed was observed in T2DM patients (P < 0.01) which strongly correlated with neutrophil activation, rolling ligand P-selectin glycoprotein ligand 1 (PSGL-1) expression, as well as established cardiovascular risk factors (cholesterol, high-sensitive C-reactive protein (CRP) and HbA1c). Rolling phenotype can be modulated by common disease risk modifiers (metformin and pravastatin). Receiver operating characteristics (ROC) and principal component analysis (PCA) revealed neutrophil rolling as an important functional phenotype in T2DM diagnostics. These results suggest a new point-of-care testing methodology, and neutrophil rolling speed as a functional biomarker for rapid profiling of dysmetabolic subjects in clinical and patient-oriented settings. PMID- 27381676 TI - Polarization-driven catalysis via ferroelectric oxide surfaces. AB - The surface chemistry and physics of oxide ferroelectric surfaces with a fixed polarization state have been studied experimentally for some time. Here, we discuss the possibility of using these materials in a different mode, namely under cyclically changing polarization conditions achievable via periodic perturbations by external fields (e.g., temperature, strain or electric field). We use Density Functional Theory (DFT) and electronic structure analysis to understand the polarization-dependent surface physics and chemistry of ferroelectric oxide PbTiO3 as an example of this class of materials. This knowledge is then applied to design catalytic cycles for industrially important reactions including NOx direct decomposition and SO2 oxidation into SO3. The possibility of catalyzing direct partial oxidation of methane to methanol is also investigated. More generally, we discuss how using ferroelectrics under cyclically changing polarization conditions can help overcome some of the fundamental challenges facing the catalysis community such as the limitations imposed by the Sabatier principle and scaling relations. PMID- 27381678 TI - Hepatitis C virus core protein increases Snail expression and induces epithelial mesenchymal transition through the signal transducer and activator of transcription 3 pathway in hepatoma cells. AB - AIM: Aberrant expression of Snail, a mediator of epithelial-mesenchymal transition (EMT), is crucial for cancer invasiveness and metastasis. Although hepatitis C virus (HCV) core protein has been implicated in hepatocarcinogenesis, the relationship between HCV core and Snail expression has not been clarified. METHODS: HepG2 and Huh7 stable cell lines were established by transfection with pcDNA-HCVc. HepG2-HCVc and Huh7-HCVc cells were co-administered with AG490. Cell migration and invasiveness were tested. STAT3 and Snail expression was analyzed by Real-time PCR and Western blot. RESULTS: We found that HCV core is capable of increasing Snail expression and inducing EMT in hepatoma cells. HCV core-induced Snail expression was accompanied by activation of signal transducer and activator of transcription 3 (STAT3), inhibition of STAT3 abrogated HCV core-induced Snail expression and EMT. Furthermore, chromatin immunoprecipitation showed that phosphorylated STAT3 directly binds to the Snail promoter. CONCLUSION: Collectively, these results suggest that HCV core would play a role in hepatocellular carcinoma invasiveness and metastasis by activating the STAT3 pathway, increasing Snail expression and subsequently triggering EMT. These findings would advance the understanding of HCV-mediated invasiveness and metastasis, and might provide a new potential therapeutic target for HCV-related hepatocellular carcinoma. PMID- 27381677 TI - Navigation in bile acid chemical space: discovery of novel FXR and GPBAR1 ligands. AB - Bile acids are signaling molecules interacting with nuclear receptors and membrane G-protein-coupled receptors. Among these receptors, the farnesoid X receptor (FXR) and the membrane G-coupled receptor (GPBAR1) have gained increasing consideration as druggable receptors and their exogenous dual regulation represents an attractive strategy in the treatment of enterohepatic and metabolic disorders. However, the therapeutic use of dual modulators could be associated to severe side effects and therefore the discovery of selective GPBAR1 and FXR agonists is an essential step in the medicinal chemistry optimization of bile acid scaffold. In this study, a new series of 6-ethylcholane derivatives modified on the tetracyclic core and on the side chain has been designed and synthesized and their in vitro activities on FXR and GPBAR1 were assayed. This speculation resulted in the identification of compound 7 as a potent and selective GPBAR1 agonist and of several derivatives showing potent dual agonistic activity. PMID- 27381679 TI - The influence of different shavers on the skin quantified by non-invasive reflectance confocal microscopy. AB - BACKGROUND: The impact of personal care devices on skin is mainly assessed using subjective tools. However, new objective, accurate non-invasive in vivo imaging techniques have been developed. The aim of this study was to evaluate the ability of reflectance confocal microscopy (RCM) in quantifying morphological impact of shavers on skin. Furthermore, tape stripping (TS) as method to study morphological impact of shavers was evaluated. METHODS: In 12 healthy male subjects, for two consecutive days, a split-face test was performed in the neck; on one side a shaver was applied, while the other side was exposed to TS. The stratum corneum (SC) thickness was quantified using RCM and sensory observations were evaluated using questionnaires. RESULTS: Shavers with a different impact on skin, can be discriminated by RCM; shaver B removed more SC after application than the skin friendlier shaver A. Furthermore, the changes in SC thickness induced by TS corresponded well to that of the shavers. CONCLUSION: RCM is able to quantify the impact of different shavers on skin. Besides, TS appeared to be a suitable model mimicking the mechanical impact of shavers on skin. RCM in combination with the TS model appeared to be a suitable minimally invasive model to obtain morphological and cell biological data on skin-material interactions caused by different personal care devices. PMID- 27381681 TI - The potential of mesenchymal stromal cells in immunotherapy. PMID- 27381682 TI - Efficacy of immunotherapy for metastatic mucosal melanoma. PMID- 27381683 TI - Blinatumomab-induced donor T-cell activation for post-stem cell transplant relapsed acute CD19-positive biphenotypic leukemia. AB - Post-stem cell transplantation (SCT) relapsed acute lymphoblastic leukemia (ALL) has extremely poor prognosis with median survival of less than 1 year. Donor lymphocyte infusion, second transplantation, chemotherapy or cytokine treatment have been tried as a salvage regimen without significant clinical benefit. Recently, blinatumomab, a bispecific monoclonal antibody targeting CD3-expressing T cells and CD19-expressing B-cell lineage malignant cells demonstrated promising outcomes in relapsed/refractory ALL patients. Literature on blinatumomab use in biphenotypic ALL along with Philadelphia chromosome positive (Ph(+)) ALL is limited. We report a case of post-SCT relapsed CD19 expressing biphenotypic lymphoblastic leukemia patient who achieved complete remission after blinatumomab treatment and has lasting remission for 1 year. PMID- 27381680 TI - Efficacy and Mechanisms of Aerobic Exercise on Cancer Initiation, Progression, and Metastasis: A Critical Systematic Review of In Vivo Preclinical Data. AB - A major objective of the emerging field of exercise-oncology research is to determine the efficacy of, and biological mechanisms by which, aerobic exercise affects cancer incidence, progression, and/or metastasis. There is a strong inverse association between self-reported exercise and the primary incidence of several forms of cancer; similarly, emerging data suggest that exercise exposure after a cancer diagnosis may improve outcomes for early-stage breast, colorectal, or prostate cancer. Arguably, critical next steps in the development of exercise as a candidate treatment in cancer control require preclinical studies to validate the biological efficacy of exercise, identify the optimal "dose", and pinpoint mechanisms of action. To evaluate the current evidence base, we conducted a critical systematic review of in vivo studies investigating the effects of exercise in cancer prevention and progression. Studies were evaluated on the basis of tumor outcomes (e.g., incidence, growth, latency, metastasis), dose-response, and mechanisms of action, when available. A total of 53 studies were identified and evaluated on tumor incidence (n = 24), tumor growth (n = 33), or metastasis (n = 10). We report that the current evidence base is plagued by considerable methodologic heterogeneity in all aspects of study design, endpoints, and efficacy. Such heterogeneity precludes meaningful comparisons and conclusions at present. To this end, we provide a framework of methodologic and data reporting standards to strengthen the field to guide the conduct of high quality studies required to inform translational, mechanism-driven clinical trials. Cancer Res; 76(14); 4032-50. (c)2016 AACR. PMID- 27381686 TI - Antibody-targeted nanoparticles for cancer treatment. AB - Nanoparticles (NPs) are diverse and versatile with physical properties that can be employed for use in cancer medicine. Targeting NPs using antibodies and antibody fragments could overcome some of the limitations seen with current targeted therapies. This review will discuss the role of antibody-targeted NPs in the treatment of cancer: as delivery vehicles, targeted theranostic agents and in the evolving field of cancer hyperthermia. PMID- 27381687 TI - Immunotherapeutic implications of IL-6 blockade for cytokine storm. AB - IL-6 contributes to host defense against infections and tissue injuries. However, exaggerated, excessive synthesis of IL-6 while fighting environmental stress leads to an acute severe systemic inflammatory response known as 'cytokine storm', since high levels of IL-6 can activate the coagulation pathway and vascular endothelial cells but inhibit myocardial function. Remarkable beneficial effects of IL-6 blockade therapy using a humanized anti-IL-6 receptor antibody, tocilizumab were recently observed in patients with cytokine release syndrome complicated by T-cell engaged therapy. In this review we propose the possibility that IL-6 blockade may constitute a novel therapeutic strategy for other types of cytokine storm, such as the systemic inflammatory response syndrome including sepsis, macrophage activation syndrome and hemophagocytic lymphohistiocytosis. PMID- 27381685 TI - Rationale for immune-based therapies in Merkel polyomavirus-positive and negative Merkel cell carcinomas. AB - Merkel cell carcinoma (MCC) is a rare but often deadly skin cancer that is typically caused by the Merkel cell polyomavirus (MCPyV). Polyomavirus T-antigen oncoproteins are persistently expressed in virus-positive MCCs (~80% of cases), while remarkably high numbers of tumor-associated neoantigens are detected in virus-negative MCCs, suggesting that both MCC subsets may be immunogenic. Here we review mechanisms by which these immunogenic tumors evade multiple levels of host immunity. Additionally, we summarize the exciting potential of diverse immune based approaches to treat MCC. In particular, agents blocking the PD-1 axis have yielded strikingly high response rates in MCC as compared with other solid tumors, highlighting the potential for immune-mediated treatment of this disease. PMID- 27381688 TI - Efficacy of adoptive cellular therapy in patients with gastric cancer: a meta analysis. AB - AIM: To systemically evaluate the efficacy and safety of adoptive cellular therapy for the treatment of gastric cancer (GC). MATERIALS & METHODS: We performed a systemic review and meta-analysis of nine eligible trials with GC and evaluated the effect of adoptive cellular therapy on the overall survival (OS) rate, T-cell subsets and adverse events. RESULTS: Overall, 829 patients were involved in the analysis. Adoptive cellular therapy significantly improved the OS rate compared with the control group. Meanwhile, we observed greatly increased percentages of CD3(+), CD4(+) and CD4(+)/CD8(+) in cellular therapy groups. CONCLUSION: Adoptive cellular therapy combined with adjuvant therapy resulted in significantly better OS rates, progression-free survival and T-lymphocyte responses in patients with GC. PMID- 27381684 TI - IFN-lambda cancer immunotherapy: new kid on the block. AB - Interferon-lambda (IFN-lambda) is a new IFN type, related to IFN-alpha, that is commonly used in the clinic. However, significant side effects accompanying IFN alpha treatment limit enthusiasm for IFN-alpha. In this review, we discuss the current landscape of IFN-alpha use in oncology and describe the biologic characteristics of IFN-lambda. IFN-lambda offers unique advantages, including a more tumor cell selective targeting, lower off-target binding and an ability to generate both innate and adaptive immune responses. IFN-lambda has also demonstrated therapeutic benefit in murine cancer models. IFN-lambda may be used in clinic as a single agent or in combination with other immunotherapy agents, such as immune checkpoint inhibitors. Further clinical trials will be needed to fully elucidate the potential of this novel agent in oncology. PMID- 27381689 TI - Urology pertinent neuroendocrine tumors: focusing on renal pelvis, bladder, prostate located sympathetic functional paragangliomas. AB - Urology pertinent neuroendocrine neoplasias are more and more driving to research attractive contributions mainly as regards the urinary tract paragangliomas, besides the prostate cancer neuroendocrine differentiation. About such visceral sympathetic paragangliomas, a considerable attention is aroused by those concerning the renal pelvis, urinary bladder and, particularly, the prostate gland. Essential catecholamine/adrenergic signal-mediated pathophysiological implications and outlined diagnostic approaches are here taken into consideration. Particularly, to reach an accurate functional diagnostic assessment, both plasma and urine catecholamine level tests are required together with 123I or 131I-meta-iodobenzylguanidine (MIBG) scan while 131I-, instead of 123I-, labeled MIBG, proving to be also useful to targeted radionuclide therapy of sympathetic paragangliomas. Nevertheless, a thorough diagnostic confirmation should be obtained by a proper histologic/ immunohistochemical study, so that it respectively highlighting the typical "zellballen" cell setting and neuroendocrine tumor cell specific biomarkers such as chromogranin-A, synaptophysin, neuron-specific enolase. Open/laparoscopic/robot-assisted surgical procedures are performed under alpha1 (doxazosin, prazosin) - and beta(propranolol)-adrenergic blockade to avoid the risk of an intraoperative adrenergic signal-triggered hypertensive crisis, what moreover may occur also during cystoscopy and biopsy in case of bladder or prostate paraganglioma. Given a conceivable likeness, about some adrenergic-mediated pathophysiological implications, between prostate paraganglioma and prostate cancer neuroendocrine transdifferentiation - although as regards two obviously different diseases - a reliable pathogenetic matter concerning prostate paraganglioma is requiring novel research approaches. PMID- 27381690 TI - Comparison of minimally invasive parathyroidectomy under local anaesthesia and minimally invasive video-assisted parathyroidectomy for primary hyperparathyroidism: a cost analysis. AB - BACKGROUND: Primary hyperparathyroidism (PHPT) origins from a solitary adenoma in 70- 95% of cases. Moreover, the advances in methods for localizing an abnormal parathyroid gland made minimally invasive techniques more prominent. This study presents a micro-cost analysis of two parathyroidectomy techniques. PATIENTS AND METHODS: 72 consecutive patients who underwent minimally invasive parathyroidectomy, video-assisted (MIVAP, group A, 52 patients) or "open" under local anaesthesia (OMIP, group B, 20 patients) for PHPT were reviewed. Operating room, consumable, anaesthesia, maintenance costs, equipment depreciation and surgeons/anaesthesiologists fees were evaluated. The patient's satisfaction and the rate of conversion to conventional parathyroidectomy were investigated. T Student's, Kolmogorov-Smirnov tests and Odds Ratio were used for statistical analysis. RESULTS: 1 patient of the group A and 2 of the group B were excluded from the cost analysis because of the conversion to the conventional technique. Concerning the remnant patients, the overall average costs were: for Operative Room, 1186,69 ? for the MIVAP group (51 patients) and 836,11 ? for the OMIP group (p<0,001); for the Team, 122,93 ? (group A) and 90,02 ? (group B) (p<0,001); the other operative costs were 1388,32 ? (group A) and 928,23 ? (group B) (p<0,001). The patient's satisfaction was very strongly in favour of the group B (Odds Ratio 20,5 with a 95% confidence interval). CONCLUSIONS: MIVAP is more expensive compared to the "open" parathyroidectomy under local anaesthesia due to the costs of general anaesthesia and the longer operative time. Moreover, the patients generally prefer the local anaesthesia. Nevertheless, the rate of conversion to the conventional parathyroidectomy was relevant in the group of the local anaesthesia compared to the MIVAP, since the latter allows a four-gland exploration. PMID- 27381691 TI - Predictive factors of difficult procedure in octogenarians undergoing elective laparoscopic cholecystectomy: a single center experience. AB - AIM: To assess the feasibility and safety of laparoscopic cholecystectomy (LC) in very elderly patients with particular attention to the predicitive factors of difficulty. PATIENTS AND METHODS: All patients aged >= 80 undergoing elective LC for lithiasis at our institution since 1st January 2015 to 31st December 2015 were included in the study. Exclusion criteria were: a) acute cholecystitis; b) biliary pancreatitis; c) biliary tract neoplasms; d) urgent procedure. Pre-, intra- and postoperative data were recorded. RESULTS: During the study period, we performed 72 LC and we enrolled 17 patients aged >= 80 with a M:F = 5:12. Of these, 10 patients had a "difficult" cholecystectomy. In seven cases an intraoperative cholangiography (IOC) was performed. Postoperative course was regular but in two patients we had an Oddian spasm in 1st postoperative day. Female sex (p=0.03) and preoperative high level of serum amylase (p= 0.02) were significantly associated to difficult cholecystectomy in elderly patients. CONCLUSION: LC in octogenarians is feasible and safe. However, sex and serum amylase can help the surgeon to predict a more difficult procedure in elective LC. In this group of patients an approach based on the individual risk is desirable and the patient could be referred to a multidisciplinary approach. PMID- 27381692 TI - A rare variant of knee dislocation. AB - Knee dislocation is a rare injury. It represents less than 0.2% of orthopaedic injuries. This case reports a rare form of knee dislocation caused by the impact of a high-energy trauma. In these cases the appropriate assessment and management is needed to ensure that patient receives the proper treatment. PMID- 27381693 TI - Complication of endoscopic tattooing: a case report of covered perforation. AB - AIM: Laparoscopy is considered a good approach in treatment of colorectal neoplastic diseases; the endoscopic tattooing is then recommended (Evidence Level III and grade of recommendation A) to mark a lesion or a polypectomy site for intraoperative identification. We describe the case of perforation after tattoing treated conservatively. CASE REPORT: 63 years old woman, underwent colonoscopy for lipoma tattooing with India ink SPOT(r) solution kit and saline test. Immediately after the procedure the patient has been referred the appearance of colic epi-mesogastric pain and fever; Computed Tomography (CT) without MDC identified an irregular thickening of transverse colon with some microbubbles compatible with focal peritonitis. Initial paralytic ileus was present too. The blood count and metabolic panel examinations reveal a neutrophil leucocytosis (WBC: 11.000/mmc, 80% neutrophils). RESULTS: On the base of WSES sepsis severity score and recent literature patient was treated conservatively with total parenteral nutrition, and intravenous antibiotic therapy. After the resolution of fever and reactivation of peristalsis. The discharge occurred after six days with no early complications. CONCLUSION: India ink tattooing with SPOT(r) solution kit and saline test represent the first choice. It is a feasible technique although perforation is a possible complication. It may need an immediately surgical operation but in most cases a conservative management is a good and safe tool even if surgery may be attempted too. PMID- 27381694 TI - Giant endometrial cyst of the liver: a case report and review of the literature. AB - Endometriosis is a benign condition described as the presence of endometrial- like tissue found outside the uterine cavity. Hepatic endometriosis is one of the rarest localization of extrapelvic endometriosis, only 22 cases have been reported in the literature. The preoperative diagnosis of hepatic endometriosis is rather difficult because in about the half of the patient affected they had no history of endometriosis. Moreover radiological images reveal no characteristic findings for hepatic endometriosis. It is often described as cystic mass with or without solid component, difficult to distinguish from hepatic abscess, hematoma, cystoadenoma or malignant neoplasia. We report a case of a 27-year-old female with a large cystic mass involving the left lobe of the liver. The patient underwent laparoscopic exploration and converted to laparotomy for resection of giant hepatic endometriosis. PMID- 27381695 TI - Unusual repair in a rare case of hepatothorax due to right-sided diaphragmatic rupture: case report. AB - Intra-thoracic herniation of abdominal organs following diaphragmatic rupture represents an unusual clinical occurrence with great diagnostic difficulty. The authors present a case of right diaphragmatic rupture related to peritonitis due to perforated duodenal ulcer in previous (1 year before) thoraco-abdominal trauma with complete intra-thoracic herniation of the liver, gallbladder, ascending and transverse colon and lung collapse. The preoperative diagnosis has been based on clinical, chest X-ray, and ultrasound examination. The patient, because of very serious respiratory and hemodynamic distress, immediately underwent surgery (thoraco-laparotomic approach) with reduction of the liver, gallbladder, ascending and transverse colon in the abdominal cavity, perforated duodenal ulcer suture and repair of diaphragmatic tear using an unusual repair mode: suture of autologous fascia lata graft to the diaphragm. Postoperative chest radiography showed the normal location of right diaphragmatic border. PMID- 27381696 TI - Appendiceal mucinous neoplasms: an uncertain nosological entity. Report of a case. AB - INTRODUCTION: Appendiceal mucocele is a relatively rare condition characterized by progressive dilation of the appendix caused by intraluminal accumulation of mucoid substance. Its incidence is 0.07 - 0,63% of all appendectomies performed. CASE REPORT: We report the case of a 70-year-old man who came to our observation with gravative pain in right lower abdominal region. A computed tomography abdominal scan revealed a cystic/tubular structure like an appendicular mass with wall enhancement but without calcifications suggestive of a mucocele. Into peritoneal cavity we found profuse mucinous material with a 1,5 cm size parietal nodule. We also identified a free perforation of the cecum with consensual spillage of gelatinous material mimicking a pseudomyxoma peritonei. We decided to perform a right hemicolectomy with excision of peritoneal lesion. DISCUSSION: The controversy in the pathologic terminology can give rise to a clinical dilemma in terms of the management and follow-up plans. For mucosal hyperplasia and cystadenoma simple appendectomy is curative. Only in case of large base of implantation it may be necessary the resection of the ileum and caecum or right hemicolectomy. In case of mucinous cystoadenocarcinoma authors perform a right hemicolectomy. CONCLUSION: Appendiceal mucinous neoplasms are different pathological entities. The correct surgical management depends on size and location of lesion. A preoperative diagnosis is obviously needed in order to perform the correct treatment. CT abdominal scan is the better diagnostic tool, but different authors show their inability to reach a preoperative diagnosis in the larger majority of cases. PMID- 27381697 TI - The Rapunzel syndrome. Report of a case. AB - Trichobezoar is a rare pathology in which swallowed hairs accumulate in the stomach. An unusual form of bezoar extending from the stomach to the small intestine or beyond has been described as Rapunzel syndrome. Trichobezoars typically cause abdominal pain and nausea, but can also present as an asymptomatic abdominal mass, progressing to abdominal obstruction and perforation. Trichobezoar with Rapunzel syndrome is an uncommon diagnosis. It is predominantly found in emotionally disturbed or mentally retarded young people. The diagnosis may be suspected in young females with abdominal pain, epigastric mass and malnutrition, who have a history of trichophagia. The Authors present a case of successful laparotomy removal of a giant gastro-duodenal trichobezoar in a 9-year-old girl with a history of trichotillophagia. Physical examination revealed diffuse abdominal pain and an epigastric mass. Psychodynamic aspects, clinical manifestations, diagnosis and therapautic strategies are discussed. PMID- 27381698 TI - DIGESTIVE SURGERY Training management and innovative technology in surgery. PMID- 27381699 TI - TRAINING COURSE - MICROSURGERY IN THYROID SURGERY. PMID- 27381701 TI - Year in Review 2015: Pediatric ARDS. AB - Led by the work of the Pediatric Acute Lung Injury Consensus Conference, much was published on the topic of pediatric ARDS in 2015. Although the availability of definitive data to the pediatric practitioner for the management of infants and children with pediatric ARDS continues to lag behind that for the adult clinician, 2015 augmented the available medical literature with more information than had been seen for years. This article will review key pediatric ARDS publications with a focus on the Pediatric Acute Lung Injury Consensus Conference consensus definition, sedation management, use of high-frequency oscillatory ventilation, diagnosis of delirium, noninvasive respiratory support, lung protective ventilation, and adjunct management therapies. Despite the recent progress, additional investigation in each of these areas is essential to the continued advancement of our knowledge and, more importantly, improvements in the outcome for pediatric patients with ARDS. PMID- 27381702 TI - Year in Review 2015: Extracorporeal Membrane Oxygenation. AB - Extracorporeal membrane oxygenation (ECMO) is a modified form of cardiopulmonary bypass. Although early trials were plagued by severe bleeding and high rates of death, subsequent experience with neonates found good survival, and ECMO became an important tool in the care of critically ill infants with respiratory failure. Since the 1980s, expansion to other groups (children, patients with cardiac disease, etc) followed as experience was obtained. Today, there is a rapid growth of ECMO, especially in the adult population. To date, >73,000 patients receiving ECMO have been reported to the international Extracorporeal Life Support Organization registry. This rapid growth in the usage of ECMO has made it possible for it to be included in the management algorithm of certain disease processes, such as ARDS, cardiopulmonary arrest, and septic shock. Significant advances in technology have made it possible to support patients on ECMO for weeks or months with success. Reduction in sedative use and experience with "awake" patients has led to ambulatory and mobile ECMO. Changes in ventilator support while on ECMO, even to the point of extubation, are also occurring. This article will review briefly some of the literature related to criteria for severity of illness before ECMO and related to ECMO care and practice. Issues relating to the use of ECMO as a resuscitative tool in cardiac arrest as well as the controversial topic of volume and outcome will also be presented. PMID- 27381700 TI - Combined therapy with metformin and insulin attenuates systemic and hepatic alterations in a model of high-fat diet-/streptozotocin-induced diabetes. AB - In this study we have explored the pathogenesis of the hepatic alterations which occur in diabetes and the modulation of these complications by the combination of metformin adjunct treatment and insulin monotherapy. For this purpose, diabetic rats were treated with insulin (DM + Ins) or metformin plus insulin (DM + Met + Ins). Biochemical and cardiometabolic parameters were analysed by spectrophotometry. Intravital microscopy was used to study the hepatic microcirculation. In the liver tissue, real-time PCR was used to analyse oxidative stress enzymes, inflammatory markers and receptors for advanced glycation end products (AGE) (RAGE) gene expression. Lipid peroxidation was assessed by thiobarbituric acid reactive species (TBARs) analyses. AGE deposition and RAGE protein expression were studied by fluorescence spectrophotometry and Western blot respectively. Body weight, %HbA1c , urea, total proteins and oxidative stress parameters were found to be similarly improved by insulin or Met + Ins treatments. On the other hand, Met + Ins treatment showed a more pronounced effect on fasting blood glucose level than insulin monotherapy. Fructosamine, uric acid, creatinine, albumin and amylase levels and daily insulin dose requirements were found to be only improved by the combined Met + Ins treatment. Liver, renal and pancreatic dysfunction markers were found to be more positively affected by metformin adjunct therapy when compared to insulin treatment. Liver microcirculation damage was found to be completely protected by Met + Ins treatment, while insulin monotherapy showed no effect. Our results suggest that oxidative stress, microcirculatory damage and glycated proteins could be involved in the aetiology of liver disease due to diabetes. Additionally, metformin adjunct treatment improved systemic and liver injury in induced diabetes and showed a more pronounced effect than insulin monotherapy. PMID- 27381703 TI - Respiratory Therapists' Involvement in End-of-Life Discussions: Stepping Up to the Plate. PMID- 27381704 TI - Exercise-Induced Bronchoconstriction in College Athletes: Are We Doing Enough? PMID- 27381705 TI - When Things Don't Go as Planned: The Inherent Difficulties and Potential Insights During Quality Improvement. PMID- 27381706 TI - Comparison of Approaches to Spontaneous Breathing Trial for Extubation: Is PAV+ Better Than Other Methods? PMID- 27381707 TI - Comparison of Proportional Assist Ventilation plus, T-Tube Ventilation, and Pressure Support Ventilation as Spontaneous Breathing Trials for Extubation: A Randomized Study-Reply. PMID- 27381708 TI - FEV1/FEV6 May Misdiagnose Patients With COPD. PMID- 27381710 TI - Editor's Commentary. PMID- 27381709 TI - FEV1/FEV6 May Misdiagnose Patients With COPD-Reply. PMID- 27381711 TI - Impact of dementia on behavioral independence and disturbance. AB - AIM: Decreasing behavioral independence levels and increasing frequencies of behavioral disturbances are the most problematic aspects for people with dementia. However, the relative effects of dementia on these factors are unknown. We investigated variability in behavioral independence and disturbance profiles of patients with dementia. METHODS: This was a cross-sectional correlation study in which 70 inpatients with dementia from convalescent wards in a hospital were enrolled. We assessed cognitive impairments with the Mini-Mental State Examination, evaluated behavioral independence levels with the Functional Independence Measure and assessed frequency of behavioral disturbances with the Dementia Behavior Disturbance Scale. RESULTS: Coefficient determination was 0.395 (P < 0.0001) between the Mini-Mental State Examination and Functional Independence Measure scores, 0.261 (P < 0.0001) between the Mini-Mental State Examination and Dementia Behavior Disturbance Scale scores, and 0.355 (P < 0.0001) between the Functional Independence Measure and Dementia Behavior Disturbance Scale scores. The most easily accomplished behavioral independence was eating, and the hardest was transfer to tub/shower. The behavioral disturbance with the highest frequency was urinary incontinence, and the lowest was emptying drawers or closets. CONCLUSIONS: Moderate correlations were found between severity of dementia and behavioral independence levels and frequencies of behavioral disturbances. There were both easier and harder to accomplish behaviors, and both higher and lower frequencies of behavioral disturbances. Geriatr Gerontol Int 2017; 17: 605-613. PMID- 27381712 TI - Retinal Neurodegeneration Associated With Peripheral Nerve Conduction and Autonomic Nerve Function in Diabetic Patients. AB - OBJECTIVE: In this study, we evaluated the correlation of retinal thickness with peripheral nerve conduction and autonomic nerve function in diabetic patients. DESIGN: Cross-sectional study. METHODS: Medical records of 160 patients (mean age, 63.61 +/- 12.52 years) with diabetes without diabetic retinopathy or mild nonproliferative diabetic retinopathy (NPDR) were reviewed. The mean retinal thickness of the parafoveal area and ganglion cell/inner plexiform layer (GC-IPL) thickness in 6 macular regions were measured using optical coherence tomography. Peripheral nerve conduction studies were conducted on peroneal and posterior tibial motor nerves and the sural sensory nerve. Five cardiovascular autonomic function tests were performed. We classified patients into groups by severity of peripheral neuropathy and autonomic dysfunction and analyzed the correlations with mean retinal thickness. RESULTS: The mean retinal thickness of the parafovea was 315.05 +/- 12.70 MUm and mean macular GC-IPL thickness was 79.89 +/- 4.70 MUm. Macular GC-IPL thickness showed significant correlation with peripheral nerve conduction (no peripheral neuropathy vs definite peripheral neuropathy: 82.0 +/- 4.8 MUm vs 75.2 +/- 3.8 MUm, P < .001). GC-IPL thickness decreased with severity of autonomic nerve dysfunction (no/mild dysfunction vs severe dysfunction: 81.2 +/- 6.6 MUm vs 77.6 +/- 5.9 MUm, P = .005). There was no significant correlation between the retinal thickness of the parafovea and electrodiagnostic tests. CONCLUSION: The decrease of GC-IPL thickness was positively correlated with both peripheral nerve conduction and autonomic nerve function in diabetic patients who presented with no diabetic retinopathy or mild NPDR. PMID- 27381713 TI - Fundus Photography as a Screening Method for Diabetic Retinopathy in Children With Type 1 Diabetes: Outcome of the Initial Photography. AB - PURPOSE: To determine the success rate of the initial fundus photography session in producing gradable images for screening diabetic retinopathy in children <18 years of age with type 1 diabetes (T1D), and to analyze outcome-associated factors. DESIGN: Retrospective observational cohort study. METHODS: Mydriatic red free monochromatic 60-degree digital fundus images centered on the macula and optic disc of 213 patients were graded. Photography success was classified as "complete" if both images of both eyes were gradable, "partial" if both images of 1 eye were gradable, "macula-centered image(s) only" if only the macula-centered image of one or both eyes was gradable, and "unsuccessful" if neither macula centered image was gradable. RESULTS: Complete success was reached in 97 (46%; 95% confidence interval [CI], 39-52) patients, at least partial success in 153 (72%; 95% CI, 65-78) patients, success of macula-centered image(s) only in 47 (22%; 95% CI, 17-28) patients, and in 13 (6%; 95%CI, 3-10) patients fundus photography was unsuccessful. Macula-centered images were more often gradable in both eyes than optic disc-centered images (P < .001). Success of photography did not differ between right and left eye. Sex, age at diagnosis of T1D, and the duration of diabetes, age, and glycemic control at the time of initial photography were unassociated with complete success. Partial success tended to decrease with increasing age category (P = .093), and the frequency of gradable macula-centered image(s) only increased with increasing age (P = .043). CONCLUSIONS: Less than half of the children achieved complete success, but in only 6% initial fundus photography was unsuccessful, indicating its value in assessing retinopathy in the pediatric setting. PMID- 27381714 TI - Harlequin ichthyosis: a novel compound mutation of ABCA12 with prenatal diagnosis. AB - Harlequin ichthyosis (HI) is the most severe form of recessive congenital ichthyosis, and is frequently lethal. We describe a family with prenatal diagnosis of HI in two siblings. We applied genomic capture and massively parallel sequencing to detect all mutations in 20 genes, including ABCA12, with inherited mutations that predispose to congenital ichthyosis. Sequence analysis of the ABCA12 gene identified two mutations, c.5232 G>A (p.Trp1744*) in exon 34 and c.6443 C>A (p.Pro2148Gln) in exon 44, each in a heterozygous state. Sanger sequencing confirmed that each parent was a heterozygous carrier for one of the variants. The spectrum of mutations identified in this study and previous studies reveals a novel compound mutation of ABCA12. PMID- 27381715 TI - Perfluorodecyltrichlorosilane-based seed-layer for improved chemical vapour deposition of ultrathin hafnium dioxide films on graphene. AB - We investigate the use of perfluorodecyltrichlorosilane-based self-assembled monolayer as seeding layer for chemical vapour deposition of HfO2 on large area CVD graphene. The deposition and evolution of the FDTS-based seed layer is investigated by X-ray photoelectron spectroscopy, Auger electron spectroscopy, and transmission electron microscopy. Crystalline quality of graphene transferred from Cu is monitored during formation of the seed layer as well as the HfO2 growth using Raman spectroscopy. We demonstrate that FDTS-based seed layer significantly improves nucleation of HfO2 layers so that graphene can be coated in a conformal way with HfO2 layers as thin as 10 nm. Proof-of-concept experiments on 200 mm wafers presented here validate applicability of the proposed approach to wafer scale graphene device fabrication. PMID- 27381716 TI - Rapid biodegradation of aflatoxin B1 by metabolites of Fusarium sp. WCQ3361 with broad working temperature range and excellent thermostability. AB - BACKGROUND: Contamination of food and feed by aflatoxin B1 (AFB1) poses serious economic and health problems worldwide, so the development of biological methods for effective AFB1 degradation is strongly required. RESULTS: Among three AFB1 degrading microorganisms isolated from moldy peanut, Fusarium sp. WCQ3361 could remove AFB1 extremely effectively, with a degradation ratio of 70.20% after 1 min and 95.38% after 24 h. Its degradation ratio was not much affected by temperature change (0-90 degrees C) and it also displayed excellent thermostability, maintaining 99.40% residual activity after boiling for 10 min. Since protease K could reduce the AFB1 degradation ratio by 55.15%, it is proposed that the effective component for AFB1 degradation is a protein. The AFB1 degradation ability of Fusarium sp. WCQ3361 was further verified by feed stock detoxification and the MTT test with HepG2 cells. In addition, no degradation products were detected by preliminary liquid chromatography/mass spectrometry, suggesting that AFB1 might be metabolized to products with different chemical characteristics from AFB1. CONCLUSION: Fusarium sp. WCQ3361 is the first reported AFB1 degradation fungus belonging to the genus Fusarium with broad working temperature range, excellent thermostability and high activity, which provides a potential highly useful solution for dealing with AFB1 contamination in the human diet and animal feed. (c) 2016 Society of Chemical Industry. PMID- 27381717 TI - Neuro-immune lessons from an annelid: The medicinal leech. AB - An important question that remains unanswered is how the vertebrate neuroimmune system can be both friend and foe to the damaged nervous tissue. Some of the difficulty in obtaining responses in mammals probably lies in the conflation in the central nervous system (CNS), of the innate and adaptive immune responses, which makes the vertebrate neuroimmune response quite complex and difficult to dissect. An alternative strategy for understanding the relation between neural immunity and neural repair is to study an animal devoid of adaptive immunity and whose CNS is well described and regeneration competent. The medicinal leech offers such opportunity. If the nerve cord of this annelid is crushed or partially cut, axons grow across the lesion and conduction of signals through the damaged region is restored within a few days, even when the nerve cord is removed from the animal and maintained in culture. When the mammalian spinal cord is injured, regeneration of normal connections is more or less successful and implies multiple events that still remain difficult to resolve. Interestingly, the regenerative process of the leech lesioned nerve cord is even more successful under septic than under sterile conditions suggesting that a controlled initiation of an infectious response may be a critical event for the regeneration of normal CNS functions in the leech. Here are reviewed and discussed data explaining how the leech nerve cord sensu stricto (i.e. excluding microglia and infiltrated blood cells) recognizes and responds to microbes and mechanical damages. PMID- 27381718 TI - Behavioral fever in ectothermic vertebrates. AB - Fever is an evolutionary conserved defense mechanism which is present in both endothermic and ectothermic vertebrates. Ectotherms in response to infection can increase their body temperature by moving to warmer places. This process is known as behavioral fever. In this review, we summarize the current knowledge on the mechanisms of induction of fever in mammals. We further discuss the evolutionary conserved mechanisms existing between fever of mammals and behavioral fever of ectothermic vertebrates. Finally, the experimental evidences supporting an adaptive value of behavioral fever expressed by ectothermic vertebrates are summarized. PMID- 27381719 TI - Effective educator-student relationships in nursing education to strengthen nursing students' resilience. AB - BACKGROUND: Little research has been conducted in private nursing schools with regard to the educator-student relationship to strengthen the resilience of nursing students and to improve the educator-student relationship. An effective educator-student relationship is a key factor to ensure a positive learning climate where learning can take place and resilience can be strengthened. PURPOSE: The purpose was to explore and describe nursing students' view on the basic elements required for an effective educator-student relationship to strengthen their resilience and the educator-student relationship. METHOD: This study followed an explorative, descriptive and contextual qualitative design in a private nursing education institution in the North West Province. Purposive sampling was used. The sample consisted of 40 enrolled nursing auxiliary students. The World Cafe Method was used to collect data, which were analysed by means of content analysis. RESULTS: The following five main themes were identified and included: (1) teaching-learning environment, (2) educator-student interaction, (3) educator qualities, (4) staying resilient and (5) strategies to strengthen resilience. CONCLUSION: Students need a caring and supportive environment; interaction that is constructive, acknowledges human rights and makes use of appropriate non-verbal communication. The educator must display qualities such as love and care, respect, responsibility, morality, patience, being open to new ideas, motivation, willingness to 'go the extra mile' and punctuality. Students reported on various ways how they manage to stay resilient. It thus seems that basic elements required in an effective educator-student relationship to strengthen the resilience of students include the environment, interaction, educator and student's qualities and resilience. PMID- 27381720 TI - Social factors determining maternal and neonatal mortality in South Africa: A qualitative study. AB - BACKGROUND: South Africa's maternal mortality ratio has increased from 150/100 000 in 1990 to 269/100 000 live births in 2015 against the Millennium Development Goals 5 (MDG5) target of 38/100 000, indicating slow progress in improving maternal health. The neonatal mortality rate was 14/1000 live births against the MDG4 target of 7/1000. The purpose of the article was to outline the socio economic factors that determine maternal and neonatal mortality in South African communities. OBJECTIVES: To identify and describe the social determinants of maternal and neonatal mortality in South Africa. METHOD: A qualitative study using audio-taped individual interviews was conducted. The interviews included 10 pregnant women who were purposefully recruited from the antenatal clinic attendees in a public hospital. The interviews were conducted in isiZulu and later translated into English by the researcher who is fluent in both. Data were analysed using the World Health Organization's (WHO) Commission on Social Determinants of Health framework. RESULTS: Findings revealed that poverty was an underlying factor to the vulnerability to illness and death of the mothers and their neonates. Other determinants were found to be the nutritional inadequacies, neglect and abuse by male partners, HIV or AIDS, inattention to reproductive health and violation of reproductive rights, and powerlessness of women and health system issues such as poor quality and incompetent health care. CONCLUSION: It is apparent that poverty plays a major role in determining the health of mothers and neonates. This requires more coordinated multi-sectorial interventions to address both the social determinants and direct causes of maternal and neonatal deaths. PMID- 27381721 TI - The needs of families accompanying injured patients into the emergency department in a tertiary hospital in Gauteng. AB - BACKGROUND: Families are not prepared for traumatic injuries of loved ones. Emergency nurses have the important role of caring for patients and families in this time of crisis. Family needs in the critical care setting have been explored using the Critical Care Family Needs Inventory (CCFNI), however little is known about family needs in the emergency department. OBJECTIVES: This study sought to determine the needs of family members accompanying injured patients into the emergency department, and if these needs were met. METHODS: A quantitative, descriptive, study was conducted in a level 1 trauma facility in Johannesburg, South Africa. The population included families of patients admitted to the emergency department, sampling 100 participants. The instrument, based on the CCFNI, was validated in a pilot study in Melbourne, Australia and re-evaluated using the Cronbach Alpha validity test to ensure internal consistency.Five themes were explored: 'meaning', 'proximity', 'communication', 'comfort' and 'support' and data were analysed using descriptive statistics. Responses to open-ended questions were analysed using content analysis. Permission from the Human Research Ethics Committee was granted and participants were ensured confidentiality and the option for counselling if required. RESULTS: Themes ranked highly important were 'meaning' and 'communication'. Satisfaction was highest for 'meaning'. Low satisfaction levels for 'communication' were found. Issues regarding prolonged time spent in the emergency department and discrimination were raised. CONCLUSION: These findings have a negative impact on the family's satisfaction with care and it is recommended that the nurse's role in family care be further explored and emphasised. PMID- 27381722 TI - Palliative care needs in Malawi: Care received by people living with HIV. AB - BACKGROUND: Infection with human immunodeficiency virus (HIV) has changed from an acute to a chronic illness in the past decade, because of highly active antiretroviral therapy (ART). Malawi's response to the HIV challenge included provision of ART for people living with HIV or AIDS (PLWHA), which significantly reduced HIV- and AIDS-related mortality. In addition, palliative care for PLWHA was introduced as a strategy that improves the success of ART. OBJECTIVE: The purpose of the study was to explore the needs of PLWHA concerning care received from primary caregivers and palliative care nurses in Malawi. METHODS: A qualitative, explorative design was used and 18 participants were selected purposefully and interviewed individually using a semi-structured interview guide. Data were analysed using NVivo software package version 10. RESULTS: Results revealed that PLWHA needed physical care from the primary caregivers due to severity of illness, integration of healthcare services, and continuity of care and proper care from nurses. They also needed knowledge from nurses in several areas which affected decision-making and needed financial and nutritional support. CONCLUSION: More could be done in meeting needs of PLWHA to improve their health and survival and assist them to achieve a better quality of life. PMID- 27381723 TI - Lived experiences of student nurses caring for intellectually disabled people in a public psychiatric institution. AB - BACKGROUND: Caring for intellectually disabled people can be demanding for student nurses who are novices in the nursing profession. To ensure that quality nursing care is provided, student nurses should have an understanding of and a positive attitude towards intellectually disabled people. Nursing intellectually disabled people can be a challenge for the student nurses. Therefore, student nurses need to be able to deal with challenges of caring for intellectually disabled people. OBJECTIVE: This article aims to explore and describe experiences of student nurses caring for intellectually disabled people in a public psychiatric institution. DESIGN AND METHOD: A qualitative, exploratory, descriptive and contextual research design was used. Data were collected through individual in-depth phenomenological interviews, naive sketches and field notes. Thematic analysis was utilised to analyse the collected data. Results were contextualised within the literature and measures to ensure trustworthiness were adhered to. Ethical principals were also applied throughout the research process. RESULTS: Five themes emerged from the data. Student nurses experienced a profoundly unsettling impact on their whole being when caring for intellectually disabled people; they developed a sense of compassion and a new way of looking at life, and experienced a need for certain physical, mental and spiritual needs to be met. CONCLUSION: From the results, it is evident that student nurses were challenged in caring for intellectually disabled people. However, they developed a sense of awareness that intellectually disabled people have a need to be cared for like any other person. PMID- 27381724 TI - Learning to Trust Flu Shots: Quasi-Experimental Evidence from the 2009 Swine Flu Pandemic. AB - This paper studies consumer learning in influenza vaccination decisions. We examine consumer learning in influenza vaccine demand within a reduced form instrumental variable framework that exploits differences in risk characteristics of different influenza viruses as a natural experiment to distinguish the effects of learning based on previous influenza vaccination experiences from unobserved heterogeneity. The emergence of a new virus strain (influenza A H1N1/09) during the 2009 'Swine flu' pandemic resulted in two different vaccines being recommended for distinct population subgroups with some people, who were not usually targeted by seasonal vaccination programs, being specifically recommended for the new Swine flu vaccine. We use these differences in vaccination targeting to construct instrumental variables for estimating the effect of past influenza vaccination experiences on the demand for pandemic vaccine. We find large causal effects of previous seasonal vaccination on pandemic vaccination. Causal effects of past influenza vaccination experiences on perceived vaccination safety are likely to be an important pathway linking past vaccination experiences with future vaccine uptake. Our results suggest a significant role of learning in vaccination decisions. Current efforts to expand seasonal vaccination may thus have potentially important long-term effects on future influenza vaccination levels and pandemic preparedness. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27381725 TI - Nickel-Catalyzed Methylation of Aryl Halides with Deuterated Methyl Iodide. AB - A nickel-catalyzed methylation of aryl halides with cheap and readily available CH3 I or CD3 I is described. The reaction is applicable to a wide range of substrates and allows installation of a CD3 group under mild reaction conditions without deuterium scrambling to other carbon atoms. Initial mechanistic studies on the stoichiometric and catalytic reactions of the isolated [(dppp)Ni(C6 H4 -4 CO2 Et)Br] [dppp=1,3-bis(diphenylphosphanyl)propane] suggest that a Ni(0) /Ni(II) catalytic cycle is favored. PMID- 27381726 TI - STAT3 signal that mediates the neural plasticity is involved in willed-movement training in focal ischemic rats. AB - Willed-movement training has been demonstrated to be a promising approach to increase motor performance and neural plasticity in ischemic rats. However, little is known regarding the molecular signals that are involved in neural plasticity following willed-movement training. To investigate the potential signals related to neural plasticity following willed-movement training, littermate rats were randomly assigned into three groups: middle cerebral artery occlusion, environmental modification, and willed-movement training. The infarct volume was measured 18 d after occlusion of the right middle cerebral artery. Reverse transcription-polymerase chain reaction (PCR) and immunofluorescence staining were used to detect the changes in the signal transducer and activator of transcription 3 (STAT3) mRNA and protein, respectively. A chromatin immunoprecipitation was used to investigate whether STAT3 bound to plasticity related genes, such as brain-derived neurotrophic factor (BDNF), synaptophysin, and protein interacting with C kinase 1 (PICK1). In this study, we demonstrated that STAT3 mRNA and protein were markedly increased following 15-d willed movement training in the ischemic hemispheres of the treated rats. STAT3 bound to BDNF, PICK1, and synaptophysin promoters in the neocortical cells of rats. These data suggest that the increased STAT3 levels after willed-movement training might play critical roles in the neural plasticity by directly regulating plasticity related genes. PMID- 27381728 TI - Thyroid dysfunction, either hyper or hypothyroidism, promotes gallstone formation by different mechanisms. AB - We have investigated comprehensively the effects of thyroid function on gallstone formation in a mouse model. Gonadectomized gallstone-susceptible male C57BL/6 mice were randomly distributed into three groups each of which received an intervention to induce hyperthyroidism, hypothyroidism, or euthyroidism. After 5 weeks of feeding a lithogenic diet of 15% (w/w) butter fat, 1% (w/w) cholesterol, and 0.5% (w/w) cholic acid, mice were killed for further experiments. The incidence of cholesterol monohydrate crystal formation was 100% in mice with hyperthyroidism, 83% in hypothyroidism, and 33% in euthyroidism, the differences being statistically significant. Among the hepatic lithogenic genes, Trbeta was found to be up-regulated and Rxr down-regulated in the mice with hypothyroidism. In contrast, Lxralpha, Rxr, and Cyp7alpha1 were up-regulated and Fxr down regulated in the mice with hyperthyroidism. In conclusion, thyroid dysfunction, either hyperthyroidism or hypothyroidism, promotes the formation of cholesterol gallstones in C57BL/6 mice. Gene expression differences suggest that thyroid hormone disturbance leads to gallstone formation in different ways. Hyperthyroidism induces cholesterol gallstone formation by regulating expression of the hepatic nuclear receptor genes such as Lxralpha and Rxr, which are significant in cholesterol metabolism pathways. However, hypothyroidism induces cholesterol gallstone formation by promoting cholesterol biosynthesis. PMID- 27381727 TI - Cognitive-enhancing effects of hydrolysate of polygalasaponin in SAMP8 mice. AB - OBJECTIVES: The aim of the study is to evaluate the cognitive-enhancing effects of hydrolysate of polygalasaponin (HPS) on senescence accelerate mouse P8 (SAMP8) mice, an effective Alzheimer's disease (AD) model, and to research the relevant mechanisms. METHODS: The cognitive-enhancing effects of HPS on SAMP8 mice were assessed using Morris water maze (MWM) and step-through passive avoidance tests. Then N-methyl-D-aspartate (NMDA) receptor subunit expression for both the cortex and hippocampus of mice was observed using Western blotting. RESULTS: HPS (25 and 50 mg/kg) improved the escape rate and decreased the escape latency and time spent in the target quadrant for the SAMP8 mice in the MWM after oral administration of HPS for 10 d. Moreover, it decreased error times in the passive avoidance tests. Western blotting showed that HPS was able to reverse the levels of NMDAR1 and NMDAR2B expression in the cortex or hippocampus of model mice. CONCLUSIONS: The present study suggested that HPS can improve cognitive deficits in SAMP8 mice, and this mechanism might be associated with NMDA receptor (NMDAR) related pathways. PMID- 27381729 TI - A pilot study on using chlorine dioxide gas for disinfection of gastrointestinal endoscopes. AB - OBJECTIVES: This pilot study of employing chlorine dioxide (CD) gas to disinfect gastrointestinal endoscopes was conducted to meet the expectations of many endoscopy units in China for a high-efficiency and low-cost disinfectant. METHODS: An experimental prototype with an active circulation mode was designed to use CD gas to disinfect gastrointestinal endoscopes. One type of testing device composed of polytetrafluoroethylene (PTFE) tubes (2 m long, inner diameter 1 mm) and bacterial carrier containers was used to simulate the channel of the endoscope. PTFE bacterial carriers inoculated with Bacillus atrophaeus with or without organic burden were used to evaluate the sporicidal activity of CD gas. Factors including exposure dosage, relative humidity (RH), and flow rate (FR) influencing the disinfection effect of CD gas were investigated. Moreover, an autoptic disinfecting test on eight real gastrointestinal endoscopes after clinical use was performed using the experimental prototype. RESULTS: RH, exposure dosage, organic burden, and the FR through the channel significantly (P<0.05) affected the disinfection efficacy of CD gas for a long and narrow lumen. The log reduction increased as FR decreased. Treatment with 4 mg/L CD gas for 30 min at 0.8 L/min FR and 75% RH, resulted in complete inactivation of spores. Furthermore, all eight endoscopes with a maximum colony-forming unit of 915 were completely disinfected. The cost was only 3 CNY (0.46 USD) for each endoscope. CONCLUSIONS: The methods and results reported in this study could provide a basis for further studies on using CD gas for the disinfection of endoscopes. PMID- 27381730 TI - Cholangiocarcinoma-derived exosomes inhibit the antitumor activity of cytokine induced killer cells by down-regulating the secretion of tumor necrosis factor alpha and perforin. AB - OBJECTIVE: The aim of our study is to observe the impact of cholangiocarcinoma derived exosomes on the antitumor activities of cytokine-induced killer (CIK) cells and then demonstrate the appropriate mechanism. METHODS: Tumor-derived exosomes (TEXs), which are derived from RBE cells (human cholangiocarcinoma line), were collected by ultracentrifugation. CIK cells induced from peripheral blood were stimulated by TEXs. Fluorescence-activated cell sorting (FACS) was performed to determine the phenotypes of TEX-CIK and N-CIK (normal CIK) cells. The concentrations of tumor necrosis factor-alpha (TNF-alpha) and perforin in the culture medium supernatant were examined by using an enzyme-linked immunosorbent assay (ELISA) kit. A CCK-8 kit was used to evaluate the cytotoxic activity of the CIK cells to the RBE cell line. RESULTS: The concentrations of TNF-alpha and perforin of the group TEX-CIK were 138.61 pg/ml and 2.41 ng/ml, respectively, lower than those of the group N-CIK 194.08 pg/ml (P<0.01) and 3.39 ng/ml (P<0.05). The killing rate of the group TEX-CIK was 33.35%, lower than that of the group N-CIK (47.35% (P<0.01)). The population of CD3(+), CD8(+), NK (CD56(+)), and CD3(+)CD56(+) cells decreased in the TEX-CIK group ((63.2+/-6.8)%, (2.5+/-1.0)%, (0.53+/-0.49)%, (0.45+/-0.42)%) compared with the N-CIK group ((90.3+/-7.3)%, (65.7+/-3.3)%, (4.2+/-1.2)%, (15.2+/-2.7)%), P<0.01. CONCLUSIONS: Our results suggest that RBE cells-derived exosomes inhibit the antitumor activity of CIK cells by down-regulating the population of CD3(+), CD8(+), NK (CD56(+)), and CD3(+)CD56(+) cells and the secretion of TNF-alpha and perforin. TEX may play an important role in cholangiocarcinoma immune escape. PMID- 27381731 TI - Vitamin D status among infants, children, and adolescents in southeastern China. AB - OBJECTIVE: Vitamin D deficiency and insufficiency are global public health problems, which must first be identified before they can be appropriately addressed, and yet information is strikingly lacking in most parts of the Asia and Pacific region. The study aimed to document and account for the actual situation in Wenzhou on the southeastern coast of China. SUBJECTS AND METHODS: Serum 25-hydroxyvitamin D levels among a total of 5845 infants, preschool children, school children, and adolescents aged 1-18 years were examined between March 2014 and February 2015. RESULTS: Their mean levels were (110.2+/-26.8), (77.5+/-25.7), (55.6+/-15.4), and (47.2+/-13.9) nmol/L, respectively. Older age groups were involved in increasing risk of vitamin D deficiency and insufficiency. There were significant seasonal differences in its median level and prevalence of deficiency and insufficiency among school children and adolescents, but there was no significant sex difference in mean level and prevalence in any age group. CONCLUSIONS: Vitamin D deficiency and insufficiency were prevalent among infants, preschool children, school children, and adolescents in Wenzhou. A vitamin D-rich diet and outdoor activities for 1-2 h per day under the natural conditions favorable to its endogeous synthesis do not suffice. The vitamin D status in Wenzhounese infants excelling over that in the US was the result of its supplementation thanks to the Chinese Medical Association recommendations, which should be consequently extended to more age groups. Life style shaped by socio-economic environments affects vitamin D status. Knowledge on the importance of vitamin D for healthy growth should be popularized. PMID- 27381732 TI - Learning curves of percutaneous endoscopic lumbar discectomy in transforaminal approach at the L4/5 and L5/S1 levels: a comparative study. AB - OBJECTIVES: This study aimed to compare the learning curves of percutaneous endoscopic lumbar discectomy (PELD) in a transforaminal approach at the L4/5 and L5/S1 levels. METHODS: We retrospectively reviewed the first 60 cases at the L4/5 level (Group I) and the first 60 cases at the L5/S1 level (Group II) of PELD performed by one spine surgeon. The patients were divided into subgroups A, B, and C (Group I: A cases 1-20, B cases 21-40, C cases 41-60; Group II: A cases 1 20, B cases 21-40, C cases 41-60). Operation time was thoroughly analyzed. RESULTS: Compared with the L4/5 level, the learning curve of transforaminal PELD at the L5/S1 level was flatter. The mean operation times of Groups IA, IB, and IC were (88.75+/-17.02), (67.75+/-6.16), and (64.85+/-7.82) min, respectively. There was a significant difference between Groups A and B (P<0.05), but no significant difference between Groups B and C (P=0.20). The mean operation times of Groups IIA, IIB, and IIC were (117.25+/-13.62), (109.50+/-11.20), and (92.15+/-11.94) min, respectively. There was no significant difference between Groups A and B (P=0.06), but there was a significant difference between Groups B and C (P<0.05). There were 6 cases of postoperative dysesthesia (POD) in Group I and 2 cases in Group IIA (P=0.27). There were 2 cases of residual disc in Group I, and 4 cases in Group II (P=0.67). There were 3 cases of recurrence in Group I, and 2 cases in Group II (P>0.05). CONCLUSIONS: Compared with the L5/S1 level, the learning curve of PELD in a transforaminal approach at the L4/5 level was steeper, suggesting that the L4/5 level might be easier to master after short-term professional training. PMID- 27381733 TI - Femoral indicator injection for transpulmonary thermodilution using the EV1000/VolumeView((r)): do the same criteria apply as for the PiCCO((r))? AB - OBJECTIVE: Comparison of global end-diastolic volume index (GEDVI) obtained by femoral and jugular transpulmonary thermodilution (TPTD) indicator injections using the EV1000/VolumnView((r)) device (Edwards Lifesciences, Irvine, USA). METHODS: In an 87-year-old woman with hypovolemic shock and equipped with both jugular and femoral vein access and monitored with the EV1000/VolumeView((r)) device, we recorded 10 datasets, each comprising duplicate TPTD via femoral access and duplicate TPTD (20 ml cold saline) via jugular access. RESULTS: Mean femoral GEDVI ((674.6+/-52.3) ml/m(2)) was significantly higher than jugular GEDVI ((552.3+/-69.7) ml/m(2)), with P=0.003. Bland-Altman analysis demonstrated a bias of (+122+/-61) ml/m(2), limits of agreement of -16 and +260 ml/m(2), and a percentage error of 22%. Use of the correction-formula recently suggested for the PiCCO((r)) device significantly reduced bias and percentage error. Similarly, mean values of parameters derived from GEDVI such as pulmonary vascular permeability index (PVPI; 1.244+/-0.101 vs. 1.522+/-0.139; P<0.001) and global ejection fraction (GEF; (24.7+/-1.6)% vs. (28.1+/-1.8)%; P<0.001) were significantly different in the case of femoral compared to jugular indicator injection. Furthermore, the mean cardiac index derived from femoral indicator injection ((4.50+/-0.36) L/(min.m2)) was significantly higher (P=0.02) than that derived from jugular indicator injection ((4.12+/-0.44) L/(min.m2)), resulting in a bias of (+0.38+/-0.37) L/(min.m2) and a percentage error of 19.4%. CONCLUSIONS: Femoral access for indicator injection results in markedly altered values provided by the EV1000/VolumeView((r)), particularly for GEDVI, PVPI, and GEF. PMID- 27381734 TI - Erratum to: Investigation of one-lung ventilation postoperative cognitive dysfunction and regional cerebral oxygen saturation relations. AB - The original version of this article unfortunately contained a mistake. In "Abstract" and the 1st para-graph of Section 2.1, the full name of the abbreviation "ASA" was incorrect in "American Standards Association (ASA)". The correct version should be "American Society of Anesthesiologists (ASA)". PMID- 27381736 TI - Response to 'Screening for risk factors: if you liked it then you should have put a number on it'. PMID- 27381737 TI - Limited responsiveness related to the minimal important difference of patient reported outcomes in rare diseases. AB - OBJECTIVES: To explore the responsiveness of patient-reported outcomes (PROs) in interventional studies involving patients with rare lysosomal storage diseases (LSDs). STUDY DESIGN AND SETTING: We searched eight databases for experimental and nonexperimental studies. Pairs of trained reviewers independently screened articles and subsequently extracted data from the eligible studies. Among studies with 10 or more patients using a valid PRO, we assessed the responsiveness of PROs based on a reanalysis of the data using minimal important difference estimates. Our analyses focused on statistically significant within-group differences in PROs for observational studies or the statistically significant between-group differences in PRO scores for controlled studies. RESULTS: Of 2,679 unique records, 62 interventional studies addressing patients with Fabry (55%), Gaucher (19%), Pompe (16%), and mucopolysaccharidoses (11%) proved eligible. The most frequently used PROs were the Short-Form-36 (25 studies), Brief Pain Inventory (20 studies), EuroQoL-5D (9 studies), and the Fatigue Severity Scale (6 studies). Observational studies suggest that PROs sometimes detect significant within-group changes when present. Randomized trials raise questions regarding the responsiveness of PROs to small differences between groups. CONCLUSIONS: Most studies have relied on generic PROs to evaluate quality of life and symptoms in patients with rare LSDs. PROs appear more responsive in observational studies than randomized trials. PMID- 27381735 TI - Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. AB - Myeloid-derived suppressor cells (MDSCs) have emerged as major regulators of immune responses in cancer and other pathological conditions. In recent years, ample evidence supports key contributions of MDSC to tumour progression through both immune-mediated mechanisms and those not directly associated with immune suppression. MDSC are the subject of intensive research with >500 papers published in 2015 alone. However, the phenotypic, morphological and functional heterogeneity of these cells generates confusion in investigation and analysis of their roles in inflammatory responses. The purpose of this communication is to suggest characterization standards in the burgeoning field of MDSC research. PMID- 27381738 TI - Management of Pituitary Disease. PMID- 27381739 TI - Students to Surgeons: Increasing Matriculation in Surgical Specialties. AB - Introduction Our nation suffers from a shortage in surgeons. This deficiency must be addressed at the medical student level. Increasing faculty and resident interaction with junior students augments surgical interest. Our surgical interest group has recently redefined its role to address these concerns. Methods A multifocal approach has been implemented to increase interest in the surgical specialties. Each academic year, senior students recruit first and second year students to our group to establish early exposure. Members receive didactic presentations from surgical faculty, addressing various topics, on a biweekly basis. In addition, scrubbing, knot-tying, and suturing workshops address technical skills throughout the semester. Membership and match data were collated and analyzed. Results Over the past 5 years, the enrollment in the student interest group increased significantly from 112 to 150. Accordingly, we have observed a parallel increase in the number of students who have successfully matched into surgical residencies. A record number of students (37) from the class of 2013 matched into surgical specialties, representing an 85% increase over the last decade. After creating bylaws and electing societal officers, the group has been recognized by the school's Student Council and given financial support. At present, the group is fiscally solvent with support from the institution, surgery department, and faculty. Conclusion As the demand for surgeons increases so too does the need to increase student interest in surgery. Our school has been successful because of our surgical interest group, and we encourage other schools to adopt a similar approach. PMID- 27381740 TI - Screening for health literacy is not the answer. PMID- 27381742 TI - Simple and Versatile Strategy to Prevent Surface Wrinkling by Visible Light Irradiation. AB - A stiff film bonded to a compliant substrate is susceptible to surface wrinkling when it is subjected to in-plane compression. Prevention of surface wrinkling is essential in many cases to maintain the integrity and functionality of this kind of system. Here we report a simple versatile technique to restrain surface wrinkling of an amorphous poly(p-aminoazobenzene) (PAAB) film by visible light irradiation. The key idea is to use the combined effects of photosoftening of the PAAB film and the stress release induced by the reversible photoisomerization. The main finding given by experiments and dimensional analysis is that the elastic modulus Ef of the film is well modulated by the ratio of light intensity and the release rate, i.e., I/V. Furthermore, the explicit solution describing the correlation of I/V with Ef is derived for the first time. The difference between the calculated critical wrinkling strain epsilonc,t based on Ef and the experimentally measured value epsilonc enables us to quantitatively evaluate the release amount of the compressive stress in the film. These key solutions provide a simple strategy to prevent the undesired surface wrinkling. Additionally, they allow us to propose a wrinkling-based technique to investigate photoinduced changes in the mechanical properties of azo-containing materials. PMID- 27381741 TI - Beyond Composite Endpoints Analysis: Semicompeting Risks as an Underutilized Framework for Cancer Research. AB - BACKGROUND: Composite endpoints (CEP), such as progression-free survival, are commonly used in cancer research. Notwithstanding their popularity, however, CEP analyses suffer from a number of drawbacks, especially when death is combined with a nonterminal event (ie, progression or recurrence), exemplifying the semicompeting risks setting. We investigated the semicompeting risks framework as a complementary analysis strategy that avoids certain drawbacks of CEPs. METHODS: The illness-death model under the semicompeting risks framework was compared with standard analysis approaches: CEP analyses and (separate) univariate analyses for each component endpoint. Data from a previously published phase III randomized clinical trial in metastatic colon cancer including 1419 participants in the N9741 trial (conducted between 1997 and 2003) were used to determine the impact of the loss of information associated with combining multiple endpoints, as well as of ignoring the potentially informative role of death. A simulation study was conducted to further explore these issues. RESULTS: Failure to account for critical features of semicompeting risks data can lead to potentially severely misleading conclusions. Advantages of semicompeting risks analyses include a clear delineation of treatment effects on both events, the ability to draw conclusions about a patient's joint risk of the two events, and an assessment of the dependence between the two event types. CONCLUSIONS: Embedding and analyzing component outcomes in the semicompeting risks framework, either as a supplement or alternative to CEP analyses, represents an important, underutilized, and feasible opportunity for cancer research. PMID- 27381744 TI - A Place for Zero in the Brain. AB - It has long been thought that the primary cognitive and neural systems responsible for processing numerosities are not predisposed to encode empty sets (i.e., numerosity zero). A new study challenges this view by demonstrating that zero is translated into an abstract quantity along the numerical continuum by the primate parietofrontal magnitude system. PMID- 27381743 TI - Quantum-enhanced multiparameter estimation in multiarm interferometers. AB - Quantum metrology is the state-of-the-art measurement technology. It uses quantum resources to enhance the sensitivity of phase estimation over that achievable by classical physics. While single parameter estimation theory has been widely investigated, much less is known about the simultaneous estimation of multiple phases, which finds key applications in imaging and sensing. In this manuscript we provide conditions of useful particle (qudit) entanglement for multiphase estimation and adapt them to multiarm Mach-Zehnder interferometry. We theoretically discuss benchmark multimode Fock states containing useful qudit entanglement and overcoming the sensitivity of separable qudit states in three and four arm Mach-Zehnder-like interferometers - currently within the reach of integrated photonics technology. PMID- 27381746 TI - Is the angulation of mandibular third molars associated with the thickness of lingual bone? AB - To find out whether the angulation of mandibular third molars is associated with the thickness of the bone at the site of impaction, and if so, which particular angulation affects the protective mechanism of the nerve, we retrospectively studied the thickness of lingual bone at the sites of impaction of 200 mandibular third molars in 149 patients using coronal, sagittal, and axial slices of cone beam computed tomograms (CT). We measured the bone at the cementoenamel junction of the mandibular second molar, at the mid-root of the third molar, and at the apex of the root. Bone less than 1mm thick was defined as "thinning". We correlated these measurements with the angulation of the tooth based on the position of the second molar and the occlusal plane in 3 dimensions: vertical, mesiobuccal, and buccolingual. The primary outcome was the thickness of the bone around the third molar. A total of 102 teeth were on the left (51%), and 125 were angulated with an occlusal plane of <85 degrees (63%). The mean (SD) thickness of bone at the cementoenamel junction of the second molar was 1.40 (0.87) mm, at mid-root 1.07 (1.03) mm, and at the apex 1.07 (1.30) mm. When the horizontal and mesioangular angulations of teeth were <85 degrees , the thickness of bone at the mid-root differed significantly from that when the vertical and distoangular angulations were 85 degrees or more (p<0.001). Correlations between the thickness of the bone and the buccolingual angulations were significantly associated with perforation of the bone at mid-root and apex (p<0.003). The bone around horizontal and mesioangular impactions was 3.6 times more likely to be "thin" than that at mid-root of vertical and distoangular third molars. A buccolingual angulation was also associated with perforation of the lingual cortex (p<0.003). As the bone was thinner at the mid-root of horizontally and mesioangularly impacted teeth, it seemed to compromise the integrity of the lingual plate, which is the natural protective barrier of the lingual nerve. These findings could be of prognostic value. PMID- 27381745 TI - Genetic enhancement of palmitic acid accumulation in cotton seed oil through RNAi down-regulation of ghKAS2 encoding beta-ketoacyl-ACP synthase II (KASII). AB - Palmitic acid (C16:0) already makes up approximately 25% of the total fatty acids in the conventional cotton seed oil. However, further enhancements in palmitic acid content at the expense of the predominant unsaturated fatty acids would provide increased oxidative stability of cotton seed oil and also impart the high melting point required for making margarine, shortening and confectionary products free of trans fatty acids. Seed-specific RNAi-mediated down-regulation of beta-ketoacyl-ACP synthase II (KASII) catalysing the elongation of palmitoyl ACP to stearoyl-ACP has succeeded in dramatically increasing the C16 fatty acid content of cotton seed oil to well beyond its natural limits, reaching up to 65% of total fatty acids. The elevated C16 levels were comprised of predominantly palmitic acid (C16:0, 51%) and to a lesser extent palmitoleic acid (C16:1, 11%) and hexadecadienoic acid (C16:2, 3%), and were stably inherited. Despite of the dramatic alteration of fatty acid composition and a slight yet significant reduction in oil content in these high-palmitic (HP) lines, seed germination remained unaffected. Regiochemical analysis of triacylglycerols (TAG) showed that the increased levels of palmitic acid mainly occurred at the outer positions, while C16:1 and C16:2 were predominantly found in the sn-2 position in both TAG and phosphatidylcholine. Crossing the HP line with previously created high-oleic (HO) and high-stearic (HS) genotypes demonstrated that HP and HO traits could be achieved simultaneously; however, elevation of stearic acid was hindered in the presence of high level of palmitic acid. PMID- 27381747 TI - New incision to harvest mandibular symphysis bone. PMID- 27381748 TI - Molecular recognition and activation by polyaza macrocyclic compounds based on host-guest interactions. AB - The design and syntheses of supramolecular hosts for the recognition and activation of molecules and anions are one of the most active research fields in supramolecular chemistry, in which polyaza macrocyclic ligands and their complexes have drawn particular attention due to their strong host-guest interactions. This review mainly focuses on the recent progress in the recognition of molecules and anions by polyaza macrocyclic compounds including polyaza macrocycles, polyaza macrobicycles and polyaza macrotricycles, as well as the activation of molecules by polyaza macrocyclic ligands and their metal complexes. PMID- 27381749 TI - Molecular changes in the postmortem parkinsonian brain. AB - Parkinson disease (PD) is the second most common neurodegenerative disease after Alzheimer disease. Although PD has a relatively narrow clinical phenotype, it has become clear that its etiological basis is broad. Post-mortem brain analysis, despite its limitations, has provided invaluable insights into relevant pathogenic pathways including mitochondrial dysfunction, oxidative stress and protein homeostasis dysregulation. Identification of the genetic causes of PD followed the discovery of these abnormalities, and reinforced the importance of the biochemical defects identified post-mortem. Recent genetic studies have highlighted the mitochondrial and lysosomal areas of cell function as particularly significant in mediating the neurodegeneration of PD. Thus the careful analysis of post-mortem PD brain biochemistry remains a crucial component of research, and one that offers considerable opportunity to pursue etiological factors either by 'reverse biochemistry' i.e. from defective pathway to mutant gene, or by the complex interplay between pathways e.g. mitochondrial turnover by lysosomes. In this review we have documented the spectrum of biochemical defects identified in PD post-mortem brain and explored their relevance to metabolic pathways involved in neurodegeneration. We have highlighted the complex interactions between these pathways and the gene mutations causing or increasing risk for PD. These pathways are becoming a focus for the development of disease modifying therapies for PD. Parkinson's is accompanied by multiple changes in the brain that are responsible for the progression of the disease. We describe here the molecular alterations occurring in postmortem brains and classify them as: Neurotransmitters and neurotrophic factors; Lewy bodies and Parkinson's-linked genes; Transition metals, calcium and calcium-binding proteins; Inflammation; Mitochondrial abnormalities and oxidative stress; Abnormal protein removal and degradation; Apoptosis and transduction pathways. This article is part of a special issue on Parkinson disease. PMID- 27381750 TI - Multicenter study on caries risk assessment in adults using survival Classification and Regression Trees. AB - Dental caries is an important public health problem worldwide. This study aims to prove how preventive therapies reduce the onset of caries in adult patients, and to identify patients with high or low risk of caries by using Classification and Regression Trees based survival analysis (survival CART). A clinical data set of 732 patients aged 20 to 64 years in nine Japanese general practices was analyzed with the following parameters: age, DMFT, number of mutans streptococci (SM) and Lactobacilli (LB), secretion rate and buffer capacity of saliva, and compliance with a preventive program. Results showed the incidence of primary carious lesion was affected by SM, LB and compliance with a preventive program; secondary carious lesion was affected by DMFT, SM and LB. Survival CART identified high risk patients for primary carious lesion according to their poor compliance with a preventive program and SM (>=10(6) CFU/ml) with a hazard ratio of 3.66 (p = 0.0002). In the case of secondary caries, patients with LB (>=10(5) CFU/ml) and DMFT (>15) were identified as high risk with a hazard ratio of 3.50 (p < 0.0001). We conclude that preventive programs can be effective in limiting the incidence of primary carious lesion. PMID- 27381751 TI - Re-irradiation of the chest wall for local breast cancer recurrence : Results of salvage brachytherapy with hyperthermia. AB - AIM: Following mastectomy and adjuvant external beam radiation therapy in patients with breast cancer, the incidence of local or locoregional recurrence is approximately 9 % (2-20 %). Alongside the often limited possibilities of surgical treatment, radiation therapy combined with superficial hyperthermia is the most effective local therapy. In the present work, a retrospective analysis of salvage brachytherapy combined with superficial hyperthermia for chest wall recurrences is presented. PATIENTS AND METHODS: Between 2004 and 2011, 18 patients with a total of 23 target volumes resulting from chest wall recurrences after previously mastectomy and external beam radiation therapy (median 56 Gy, range 50-68 Gy) were treated with superficial brachytherapy as salvage treatment: 8 patients (44 %) had macroscopic tumor, 3 (17 %) had microscopic tumor (R1), and 7 (39 %) had undergone R0 resection and were treated due to risk factors. A dose of 50 Gy was given (high-dose rate [HDR] and pulsed-dose rate [PDR] procedures). In all, 5 of 23 patients (22 %) received additional concurrent chemotherapy, and in 20 of 23 (87 %) target volumes additional superficial hyperthermia was carried out twice weekly. RESULTS: The 5-year local recurrence-free survival was 56 %, the disease free survival was 28 %, and a 5-year overall survival was 22 %. Late side effects Common Toxicity Criteria (CTC) grade 3 were reported in 17 % of the patients: 2 of 18 (11 %) had CTC grade 3 fibrosis, and 1 of 18 (6 %) had a chronic wound healing disorder. CONCLUSION: Re-irradiation as salvage brachytherapy with superficial hyperthermia for chest wall recurrences is a feasible and safe treatment with good local control results and acceptable late side effects. PMID- 27381752 TI - Towards a General Understanding of Carbonyl-Stabilised Ammonium Ylide-Mediated Epoxidation Reactions. AB - The key factors for carbonyl-stabilised ammonium ylide-mediated epoxidation reactions were systematically investigated by experimental and computational means and the hereby obtained energy profiles provide explanations for the observed experimental results. In addition, we were able to identify the first tertiary amine-based chiral auxiliary that allows for high enantioselectivities and high yields for such epoxidation reactions. PMID- 27381753 TI - Factors Explaining Variation in Alcohol Use Disorder Prevalence Across Border and Nonborder Communities in Texas. AB - BACKGROUND: U.S. border populations have been found to be at high risk for alcohol problems. However, results from the U.S.-Mexico Study on Alcohol and Related Conditions (UMSARC) revealed surprisingly large variation in alcohol outcomes even among Texas border sites, with alcohol use disorder (AUD) prevalence ~1.5 to 1.6 times greater in the border city of Laredo compared to both San Antonio and the border site of McAllen/Brownsville. Because a better understanding of this variation is important to identifying environmental influences on AUD, we developed and tested a conceptual model addressing variation in AUD prevalence across Texas UMSARC sites. METHODS: Surveys involved in-person, household interviews with Mexican-origin residents of the Texas border cities Laredo (n = 751) and McAllen/Brownsville (n = 814), with San Antonio as an off-border comparison (n = 771). Interviews assessed past-year DSM-5 AUD; past year heavy drinking; coping and enhancement motives; and 7 indicators of substance use climate and stress exposure hypothesized to mediate site effects. Analyses, conducted separately by gender, included regressions and structural equation modeling with Mplus. RESULTS: Preliminary analyses revealed that site effects on AUD prevalence were, unexpectedly, exclusive to men, and that Laredan men were similar to McAllen/Brownsville men on demographics, acculturation, and cross-border mobility. However, sites differed dramatically on most of the hypothesized risk factors. Structural equation models confirmed that site effects on AUD were partially mediated via effects of site on indicators of a permissive climate (i.e., permissive drinking norms, high drug availability) and stress exposures (i.e., high exposure to violence/crime, low family support), and via downstream effects on drinking motives and heavy drinking. CONCLUSIONS: Findings of very high rates of past-12-month AUD among Laredan men (35%) suggest the possibility of significant heterogeneity even within demographically similar border areas and underline the need for additional study of the border region. Findings regarding our conceptual model suggest that this model may constitute a useful initial framework for future research on alcohol problems at the border. However, additional research using representative samples is needed to confirm and expand this model to comprehensively address relevant individual and community factors. PMID- 27381754 TI - Prevalence and Risk Factors Associated With Hypertension in Hemophilia: Cross Sectional Analysis of a National Discharge Register. AB - INTRODUCTION: Improved life expectancy of persons with hemophilia (PWHs) has led to a greater interest in the role of age-related chronic diseases, such as hypertension, in this cohort. Several observational studies have reported an increased prevalence of hypertension in PWHs; however, this has not been assessed using a large, national database in the United States. AIMS: We hypothesized the prevalence of hypertension is increased in PWHs and compared the prevalence of hypertension and associated risk factors among patients with and without hemophilia. METHODS: A cross-sectional analysis was performed using discharge data among adult males from the National Inpatient Sample over the 3-year period, 2009 to 2011. Hypertension was compared across groups using Rao-Scott chi2 test. Multivariable logistic regression was used to estimate the odds of hypertension in patients with hemophilia after adjustment for hypertension-associated risk factors. RESULTS: The prevalence of hypertension in patients with hemophilia was less than the prevalence of hypertension in patients without hemophilia (39.5% vs 56.3%, P < .001). Hemophilia was associated with a decreased odds of hypertension after adjusting for associated risk factors (odds ratio: 0.87; 95% confidence interval: 0.81-0.94). CONCLUSION: In contrast to the findings of several other recent studies, we report a decreased prevalence of hypertension in PWHs. The discrepancy among the reported prevalence of hypertension in our study and several others highlights the potential biases inherent to retrospective and cross-sectional studies and underscores the need for well-designed prospective studies to determine the true incidence of hypertension in PWHs, which may lie somewhere in between our findings and the findings of others. PMID- 27381755 TI - Comorbidities Must Be Considered in Mean Platelet Volume Measurement in Patients With Idiopathic Pulmonary Fibrosis. PMID- 27381756 TI - Further Insights in the Most Common SCN5A Mutation Causing Overlapping Phenotype of Long QT Syndrome, Brugada Syndrome, and Conduction Defect. AB - BACKGROUND: Phenotypic overlap of type 3 long QT syndrome (LQT3), Brugada syndrome (BrS), cardiac conduction disease (CCD), and sinus node dysfunction (SND) is observed with SCN5A mutations. SCN5A-E1784K is the most common mutation associated with BrS and LQTS3. The present study examines the genotype-phenotype relationship in a large family carrying SCN5A-E1784K and SCN5A-H558R polymorphism. METHODS AND RESULTS: Clinical work-up, follow-up, and genetic analysis were performed in 35 family members. Seventeen were SCN5A-E1784K positive. They also displayed QTc prolongation, and either BrS, CCD, or both. One carrier exhibited SND. The presence of SCN5A-H558R did not significantly alter the phenotype of SCN5A-E1784K carriers. Fourteen SCN5A-E1784K patients underwent implantable cardioverter-defibrillator (ICD) implantation; 4 developed VF and received appropriate ICD shocks after 8+/-3 months of follow-up. One patient without ICD also developed VF after 6.7 years. These 5 cases carried both SCN5A E1784K and SCN5A-H558R. Functional characterization was achieved by expressing SCN5A variants in TSA201 cells. Peak (INa,P) or late (INa,L) sodium currents were recorded using whole-cell patch-clamp techniques. Co-expression of SCN5A-E1784K and SCN5A-WT reduced INa,P to 70.03% of WT, shifted steady-state inactivation by 11.03 mV, and increased INa,L from 0.14% to 1.86% of INa,P. Similar changes were observed when SCN5A-E1784K was co-expressed with SCN5A-H558R. CONCLUSIONS: We demonstrate a strong genotype-phenotype correlation with complete penetrance for BrS, LQTS, or CCD in the largest family harboring SCN5A-E1784K mutation described so far. Phenotype of LQTS is present during all decades of life, whereas CCD develops with increasing age. Phenotypic overlap may explain the high event rate in carriers. PMID- 27381757 TI - Twenty-Five Year Secular Trends in Lipids and Modifiable Risk Factors in a Population-Based Biracial Cohort: The Coronary Artery Risk Development in Young Adults (CARDIA) Study, 1985-2011. AB - BACKGROUND: Cross-sectional analyses suggest that total and low-density lipoprotein cholesterol (LDL-c) trends that had been declining are now reversing. We examined longitudinal data from the Coronary Artery Risk Development in Young Adults (CARDIA) study to examine secular trends in total cholesterol, LDL-c, high density lipoprotein cholesterol (HDL-c), and triglycerides over 25 years. We also assessed whether modifiable lifestyle factors (body mass index, physical activity, alcohol consumption, smoking, and lipid-lowering medications) are associated with these trends. METHODS AND RESULTS: CARDIA recruited 5115 black and white men and women ages 18 to 30 years from 4 US communities in 1985-1986, and re-examined them 5, 10, 15, 20, and 25 years later. Secular trends, modeled as age-matched time trends, were estimated using repeated-measures regression stratified on race and sex. Total cholesterol and LDL-c initially decreased ~5 to 8 mg/dL between visits before plateauing and moving toward adverse trends in all groups, except black women, by year 25. HDL-c showed an upward secular trend of 1 to 3 mg/dL between visits starting at year 15 in all groups; triglyceride trends were largely flat. Obesity and use of lipid-lowering medications, which both increased over follow-up, had strong independent, but opposite, associations with lipid trends over time. In aggregate, associations of modifiable lifestyle factors counterbalanced one another, minimally influencing secular trends. CONCLUSIONS: Over 25 years, initially favorable trends in total cholesterol and LDL-c have leveled off and may be reversing, persisting after control for modifiable risk factors. Factors such as dietary changes over 25 years and poor adherence to medications are candidates for additional investigation. PMID- 27381759 TI - Temporary Suppression of Cardiac Ganglionated Plexi Leads to Long-Term Suppression of Atrial Fibrillation: Evidence of Early Autonomic Intervention to Break the Vicious Cycle of "AF Begets AF". AB - BACKGROUND: Botulinum toxin (BTX), temporarily suppressing cholinergic transmission (<3 weeks), has been reported to suppress atrial fibrillation (AF) for >=1 year. We aimed to investigate the mechanism underlying long-term suppression of AF caused by injecting BTX into major atrial ganglionated plexi (GPs). METHODS AND RESULTS: Bilateral thoracotomies in anesthetized dogs allowed programmed stimulation at 4 pulmonary veins, biatrial appendages, and the superior vena cava to determine the effective refractory period (ERP) in the first operation. Group 1 (n=10) received BTX injection into all GPs; group 2 (n=7) received no injection. Groups 1 and 2 received rapid atrial pacing (800 bpm) 6 days a week. Group 3 (n=7) did not undergo thoracotomy or rapid atrial pacing to serve as controls for histological studies. A second operation and the same measurements were made 3 months later. During the first operation in group 1, ERPs of 4 pulmonary veins, but not biatrial appendages or superior vena cava, increased immediately after BTX injection. AF burdens increased significantly from the fifth week after the first operation in group 2 but not in group 1. In the second operation, ERPs remained unchanged compared with ERPs before BTX injection in group 1, whereas ERPs shortened significantly at all sites except the superior vena cava in group 2. There was no difference of autonomic nerve density between group 1 and group 3. The GP choline acetyltransferase (+) and atrial tyrosine hydroxylase (+) nerve densities were higher in group 2 than in group 1 and group 3. CONCLUSIONS: Temporary suppression of major atrial GPs by BTX prevents autonomic remodeling and provides long-term suppression of AF, indicating the critical role of GPs in AF progression. PMID- 27381758 TI - Zofenopril Protects Against Myocardial Ischemia-Reperfusion Injury by Increasing Nitric Oxide and Hydrogen Sulfide Bioavailability. AB - BACKGROUND: Zofenopril, a sulfhydrylated angiotensin-converting enzyme inhibitor (ACEI), reduces mortality and morbidity in infarcted patients to a greater extent than do other ACEIs. Zofenopril is a unique ACEI that has been shown to increase hydrogen sulfide (H2S) bioavailability and nitric oxide (NO) levels via bradykinin-dependent signaling. Both H2S and NO exert cytoprotective and antioxidant effects. We examined zofenopril effects on H2S and NO bioavailability and cardiac damage in murine and swine models of myocardial ischemia/reperfusion (I/R) injury. METHODS AND RESULTS: Zofenopril (10 mg/kg PO) was administered for 1, 8, and 24 hours to establish optimal dosing in mice. Myocardial and plasma H2S and NO levels were measured along with the levels of H2S and NO enzymes (cystathionine beta-synthase, cystathionine gamma-lyase, 3-mercaptopyruvate sulfur transferase, and endothelial nitric oxide synthase). Mice received 8 hours of zofenopril or vehicle pretreatment followed by 45 minutes of ischemia and 24 hours of reperfusion. Pigs received placebo or zofenopril (30 mg/daily orally) 7 days before 75 minutes of ischemia and 48 hours of reperfusion. Zofenopril significantly augmented both plasma and myocardial H2S and NO levels in mice and plasma H2S (sulfane sulfur) in pigs. Cystathionine beta-synthase, cystathionine gamma-lyase, 3-mercaptopyruvate sulfur transferase, and total endothelial nitric oxide synthase levels were unaltered, while phospho-endothelial nitric oxide synthase(1177) was significantly increased in mice. Pretreatment with zofenopril significantly reduced myocardial infarct size and cardiac troponin I levels after I/R injury in both mice and swine. Zofenopril also significantly preserved ischemic zone endocardial blood flow at reperfusion in pigs after I/R. CONCLUSIONS: Zofenopril-mediated cardioprotection during I/R is associated with an increase in H2S and NO signaling. PMID- 27381761 TI - Patterns of Carotid Intima-Media Thickness Progression in Kawasaki Patients: A Crystal Ball for Long-Term Vascular Health? PMID- 27381760 TI - Extracardial Vasculopathy After Kawasaki Disease: A Long-Term Follow-up Study. AB - BACKGROUND: Kawasaki disease (KD) is a pediatric vasculitis with coronary artery aneurysm (CAA) as a major complication. Controversy exists about cardiovascular risk later in life. The aim of our study was to evaluate whether KD patients are at increased risk, as assessed by carotid intima-media thickness (cIMT). METHODS AND RESULTS: We measured cIMT over 15 years by B-mode ultrasonography in KD patients during follow-up and in unaffected controls (mostly siblings). A multilevel, repeated-measures, linear mixed-effects model was used to evaluate the association between KD and cIMT. A total of 319 patients with 528 measurements were compared with 150 controls. In KD patients, the mean cIMT was increased compared with controls (0.375 mm [95% CI 0.372-0.378 mm] versus 0.363 mm [95% CI 0.358-0.368 mm]; P<0.001). Furthermore, mean cIMT of CAA-negative patients was 0.373 mm (P<0.01 compared with controls), of patients with small medium CAA was 0.374 mm (P<0.05 compared with controls), and of patients with giant CAA was 0.381 mm (P<0.01 compared with controls). Compared with controls, CAA-negative participants started with an increased cIMT (+0.0193+/-0.0053 mm, P<0.001) but showed slower progression (-0.0014+/-0.0006 mm/year, P=0.012). Patients with giant CAA showed a trend toward increased cIMT progression (0.0013+/-0.0007 mm/year, P=0.058). CONCLUSIONS: We observed a positive correlation between cIMT and KD severity of coronary arteritis at the acute stage. Although initially increased, the cIMT in CAA-negative patients normalized at a later age. In contrast, patients with a history of KD complicated by giant CAA showed a trend toward persistently increased cIMT. These patients may need cardiovascular counseling and follow-up beyond the heart. PMID- 27381762 TI - Patterns of 'at-home' alcohol-related injury presentations to emergency departments. AB - AIMS AND OBJECTIVES: This study aimed to establish the scale of alcohol-related injuries originating in the home. BACKGROUND: Despite recent media and public attention on alcohol-related injuries occurring at licensed venues, many occur in other locations including the home. DESIGN: A retrospective observational study. METHODS: Emergency department surveillance data sourced from the Queensland Injury Surveillance Unit were interrogated for alcohol-related emergency department presentations from 2003-2012 (n = 12,296). Descriptive analysis was undertaken to assess alcohol involvement in injury, and analysis of variance was used to determine the differences among group means and their associated presentations. The relationship between demographic variables and injury location was assessed using p value of <0.05 as statistically significant. RESULTS: Of all injuries that were positively identified as being alcohol related, 41.07% occurred at the 'other' location, 36.14% 'at home', 13.00% on the street and 9.78% at licensed premises. Of these, males (n = 2635; 59%) represented a higher proportion than females (n = 1807; 41%). Of injuries identified as domestic violence by spouse or partner (n = 510), 59.5% occurred 'at home'. CONCLUSIONS: This is the first study to investigate alcohol-related injuries occurring at home. The home accounts for a greater proportion of injuries than the frequently assessed licensed premises location. Further research is required to validate these findings in a wider setting. RELEVANCE TO CLINICAL PRACTICE: A public health campaign is required to minimise harm associated with alcohol-related injuries in the home, and nurses are positioned to inform health policy makers around this issue. Furthermore, emergency department nurses are in a unique position to provide brief interventions around safe alcohol consumption and injury prevention. PMID- 27381763 TI - Taste-Active Maillard Reaction Products in Roasted Garlic (Allium sativum). AB - In order to gain first insight into candidate Maillard reaction products formed upon thermal processing of garlic, mixtures of glucose and S-allyl-l-cysteine, the major sulfur-containing amino acid in garlic, were low-moisture heated, and nine major reaction products were isolated. LC-TOF-MS, 1D/2D NMR, and CD spectroscopy led to their identification as acortatarin A (1), pollenopyrroside A (2), epi-acortatarin A (3), xylapyrroside A (4), 5-hydroxymethyl-1-[(5 hydroxymethyl-2-furanyl)methyl]-1H-pyrrole-2-carbalde-hyde (5), 3-(allylthio)-2 (2-formyl-5-hydroxymethyl-1H-pyrrol-1-yl)propanoic acid (6), (4S)-4 (allylthiomethyl)-3,4-dihydro-3-oxo-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (7), (2R)-3-(allylthio)-2-[(4R)-4-(allylthiomethyl)-6-formyl-3-oxo-3,4 dihydropyrrolo-[1,2-a]pyrazin-2(1H)-yl]propanoic acid (8), and (2R)-3-(allylthio) 2-((4S)-4-(allylthiomethyl)-6-formyl-3-oxo-3,4-dihydropyrrolo-[1,2-a]pyrazin 2(1H)-yl)propanoic acid (9). Among the Maillard reaction products identified, compounds 5-9 have not previously been published. The thermal generation of the literature known spiroalkaloids 1-4 is reported for the first time. Sensory analysis revealed a bitter taste with thresholds between 0.5 and 785 MUmol/kg for 1-5 and 7-9. Compound 6 did not show any intrinsic taste (water) but exhibited a strong mouthfullness (kokumi) enhancing activity above 186 MUmol/kg. LC-MS/MS analysis showed 1-9 to be generated upon pan-frying of garlic with the highest concentration of 793.7 MUmol/kg found for 6, thus exceeding its kokumi threshold by a factor of 4 and giving evidence for its potential taste modulation activity in processed garlic preparations. PMID- 27381765 TI - No change in live birthweight of IVF singleton deliveries over an 18-year period despite significant clinical and laboratory changes. AB - STUDY QUESTION: Has live birthweight changed over 18 years of autologous fresh and frozen IVF? SUMMARY ANSWER: Regardless of changes in clinical care and laboratory practice over 18 years, birthweight has remained stable. WHAT IS KNOWN ALREADY: Birthweight has historically been used as a marker of neonatal health. Frozen embryo transfers lead to heavier live birthweights compared with fresh embryo transfers. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study included 7295 singletons from autologous fresh (n = 6265) and frozen (n = 1030) IVF cycles from 1996 to 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients undergoing autologous IVF cycles between 1996 and 2013 resulting in a singleton live born with a birthweight recorded were included. One-way ANOVA and t-tests compared mean live birthweight in fresh and frozen cycles in 6-month increments over 18 years. Linear regression analysis was performed to investigate predictors of birthweight. MAIN RESULTS AND THE ROLE OF CHANCE: Mean birthweight after fresh (3283 +/- 601 g) and frozen (3462 +/- 621 g) cycles were significantly different (P < 0.001). ANOVA demonstrated no significant difference in mean weight from fresh or frozen cycles over 6-month intervals. No difference in weight was noted between Days 3 and 5 transfers or between ICSI and standard IVF. No difference was found across known changes when comparing media, laboratory location, cryopreservation method or gonadotrophins. LIMITATIONS, REASONS FOR CAUTION: Limitations include the small number of frozen low birthweight neonates. WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests that changes in IVF practice, with the exception of fresh or frozen embryo transfer, have little impact on mean live birthweight. STUDY FUNDING/COMPETING INTERESTS: No funding was received for this study. The authors have no conflicting interests. TRIAL REGISTRATION NUMBER: Not applicable. PMID- 27381764 TI - Out of Africa: origins and evolution of the human malaria parasites Plasmodium falciparum and Plasmodium vivax. AB - Plasmodium falciparum and Plasmodium vivax account for more than 95% of all human malaria infections, and thus pose a serious public health challenge. To control and potentially eliminate these pathogens, it is important to understand their origins and evolutionary history. Until recently, it was widely believed that P. falciparum had co-evolved with humans (and our ancestors) over millions of years, whilst P. vivax was assumed to have emerged in southeastern Asia following the cross-species transmission of a parasite from a macaque. However, the discovery of a multitude of Plasmodium spp. in chimpanzees and gorillas has refuted these theories and instead revealed that both P. falciparum and P. vivax evolved from parasites infecting wild-living African apes. It is now clear that P. falciparum resulted from a recent cross-species transmission of a parasite from a gorilla, whilst P. vivax emerged from an ancestral stock of parasites that infected chimpanzees, gorillas and humans in Africa, until the spread of the protective Duffy-negative mutation eliminated P. vivax from human populations there. Although many questions remain concerning the biology and zoonotic potential of the P. falciparum- and P. vivax-like parasites infecting apes, comparative genomics, coupled with functional parasite and vector studies, are likely to yield new insights into ape Plasmodium transmission and pathogenesis that are relevant to the treatment and prevention of human malaria. PMID- 27381767 TI - Talk about sex. PMID- 27381766 TI - A nested case-control study of prenatal vanadium exposure and low birthweight. AB - STUDY QUESTION: Is prenatal vanadium exposure associated with adverse birth outcomes? SUMMARY ANSWER: The odds of low birthweight (LBW) are increased 2.23 fold in mothers with a urinary vanadium of >=2.91 MUg/g creatinine compared with that in mothers with a urinary vanadium of <=1.42 MUg/g creatinine. WHAT IS KNOWN ALREADY: Human exposure to vanadium occurs through intake of food, water and polluted air. Vanadium has been suggested to have fetotoxicity and developmental toxicity in animal studies, and epidemiological studies have reported an association between a decrease in birthweight and vanadium exposure estimated from particulate matter. STUDY DESIGN, SIZE, DURATION: A nested case-control study involving 816 study participants (204 LBW cases and 612 matched controls) was conducted with data from the prospective Healthy Baby Cohort between 2012 and 2014 in the province of Hubei, China. PARTICIPANTS/MATERIALS, SETTING, METHODS: Vanadium concentrations in 816 maternal urine samples collected before delivery [the median gestational age was 39 weeks (range 27-42 weeks)] were measured by inductively coupled plasma mass spectrometry. Information on the infants' birth outcomes was obtained from medical records. Conditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). MAIN RESULTS AND THE ROLE OF CHANCE: The median urinary vanadium concentration of the cases was much higher than that of the controls (3.04 MUg/g creatinine versus 1.93 MUg/g creatinine). The results revealed a significant positive trend between the odds of LBW and level of maternal urinary vanadium [relative to the lowest tertile; adjusted OR = 1.69 (95% CI: 0.92, 3.10) for the medium tertile; adjusted OR = 2.23 (95% CI: 1.23, 4.05) for the highest tertile; P-trend = 0.02]. Additionally, the association was not modified by maternal age (P for heterogeneity = 0.70) or infant gender (P for heterogeneity = 0.21). LIMITATIONS, REASONS FOR CAUTION: The maternal urine sample was collected before labor, and the maternal urinary vanadium levels measured at one point in time may not accurately reflect the vanadium burden during the entire pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study can enrich the biological monitoring data on urinary vanadium in pregnant women; and may be evidence that vanadium may affect fetal development. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Natural Science Foundation of China (21437002, 81372959 and 81402649), the R&D Special Fund for Public Welfare Industry (Environment) (201309048) and the Fundamental Research Funds for the Central Universities, HUST (2016YXZD043). The authors have no conflicts of interest to declare. PMID- 27381769 TI - Is community spirit a thing of the past? PMID- 27381768 TI - [Over 80 years and myocardial infarction]. PMID- 27381770 TI - The introduction of psychiatry in Norwegian medicine. PMID- 27381772 TI - [Not Available]. PMID- 27381771 TI - [Not Available]. PMID- 27381774 TI - [Not Available]. PMID- 27381773 TI - [Not Available]. PMID- 27381775 TI - [Not Available]. PMID- 27381777 TI - [Not Available]. PMID- 27381776 TI - [Not Available]. PMID- 27381778 TI - [Not Available]. PMID- 27381779 TI - [Cesarean section in trisomy 13 and 18 - a value-based assessment]. PMID- 27381780 TI - [Help the farmers in the fight against MRSA]. PMID- 27381781 TI - [Why does the use of coercion vary, and what can we do about it?]. PMID- 27381782 TI - [Time to introduce specialist examinations]. PMID- 27381783 TI - [Radiographers describing radiology images is not the solution]. PMID- 27381784 TI - [Treatment of air embolisms]. PMID- 27381785 TI - [Not Available]. PMID- 27381786 TI - Incentives and participation in a medical survey. AB - BACKGROUND Questionnaire surveys are important for surveying the health and disease behaviour of the population, but recent years have seen a fall in participation. Our study tested whether incentives can increase participation in these surveys.MATERIAL AND METHOD We sent a questionnaire on risk factors for colorectal cancer (height, weight, smoking, self-reported diagnoses, family medical history) to non-screened participants in a randomised colonoscopy screening study for colorectal cancer: participants who were invited but did not attend for colonoscopy examination (screening-invited) and persons who were not offered colonoscopy (control group). The persons were randomised to three groups: no financial incentive, lottery scratch cards included with the form, or a prize draw for a tablet computer when they responded to the form. We followed up all the incentive groups with telephone reminder calls, and before the prize draw for the tablet computer.RESULTS Altogether 3 705 of 6 795 persons (54.5 %) responded to the questionnaire; 43.5 % of those invited for screening and 65.6 % of the control group (p < 0.001). The proportion that answered was not influenced by incentives, either among those invited for screening (42.4 % in the non-prize group, 45.5 % in the lottery scratch card group and 42.6 % in the prize draw group; p = 0.24), or in the control group (65.6 % in the non-prize group, 66.4 % in the lottery scratch card group and 64.7 % in the prize draw group; p = 0.69). Prior to reminder calls, 39.2 % responded. A further 15.3 % responded following telephone reminder calls (14.1 % of the screening-invited and 16.5 % of the control group; p < 0.001).INTERPRETATION Incentives did not increase participation in this medical questionnaire survey. Use of telephone reminder calls and telephone interviews increased participation, but whether this is more effective than other methods requires further study. PMID- 27381787 TI - [Myasthenia gravis - optimal treatment and accurate diagnosis]. AB - Around 700 people in Norway have myasthenia gravis, an autoimmune disease that affects neuromuscular transmission and results in fluctuating weakness in some muscles as its sole symptom. The diagnosis is based on typical symptoms and findings, detection of antibodies and neurophysiological examination. Symptomatic treatment with acetylcholinesterase inhibitors is generally effective, but most patients also require immunosuppressive drug treatment. Antigen-specific therapy is being tested in experimental disease models. PMID- 27381788 TI - Intracranial artery dissection. PMID- 27381789 TI - [A woman in her seventies with rapid deterioration of cognitive impairment]. AB - We present a female patient with an unusual cause of cognitive impairment that proved to be reversible. Her case study illustrates why acute deterioration of cognitive impairment requires a thorough clinical approach. PMID- 27381790 TI - [Legal protection for the mentally ill]. PMID- 27381791 TI - [Olaf Bulls poem Metope - read as therapeutic conversation]. PMID- 27381792 TI - [Herman Wedel Major - the person, the doctor and the reformer]. PMID- 27381793 TI - [The control commission in the mental health services - Herman Wedel Majors innovation]. PMID- 27381794 TI - [Major's and Schirmer's Gaustad]. AB - The psychiatrist Herman Wedel Major planned Gaustad asylum in collaboration with his brother-in-law, the architect Heinrich Ernst Schirmer. The planning of Gaustad took place in parallel with the preparation of the first Norwegian Mental Health Act, adopted by the Storting on 30 July 1848, and Gaustad's architecture provides a good illustration of the ideals behind the mental health reform of the 19th century. In particular, Major's and Schirmer's Gaustad represents a break with Frederik Holst's ideal of the panoptic institution. Whereas Holst and his architect Christian Heinrich Grosch promoted a radial plan institution based on the type used for penitentiaries, Schirmer and Major designed a modern, pavilion style hospital with wards placed independently in the landscape. PMID- 27381795 TI - "Mentalen" - from mental hospital to madhouse in Bergen. PMID- 27381796 TI - [Many names for disease]. PMID- 27381797 TI - [Not Available]. PMID- 27381798 TI - [Not Available]. PMID- 27381799 TI - [Google doctors]. PMID- 27381800 TI - [Student substitute in general practice - which rules apply?]. PMID- 27381801 TI - [Not Available]. PMID- 27381802 TI - [Not Available]. PMID- 27381803 TI - [Not Available]. PMID- 27381804 TI - [Not Available]. PMID- 27381805 TI - [Not Available]. PMID- 27381806 TI - Comparative proteomics of umbilical vein blood plasma from normal and gestational diabetes mellitus patients reveals differentially expressed proteins associated with childhood obesity. AB - PURPOSE: Offspring obesity is one of long-term complications of gestational diabetes mellitus (GDM). The aim of this study is to identify proteins differentially expressed in the umbilical vein blood plasma, which could become markers for early diagnosis of childhood obesity. EXPERIMENTAL DESIGN: Umbilical vein plasma samples were collected from 30 control and 30 GDM patients in 2007 2008 whose offspring were suffering from obesity at 6-7 years old. Multiplexed isobaric tandem mass tag labeling combined with LC-MS/MS was used to identify differentially expressed proteins. Ingenuity pathway analysis was performed to identify canonical pathways, biological functions, and networks of interacting proteins. Western blotting was used to verify the expression of three selected proteins. RESULTS: A total of 318 proteins were identified, of which 12 proteins were upregulated in GDM group while 24 downregulated. Lipid metabolism was the top category identified by ingenuity pathway analysis. Three randomly chosen proteins were validated by Western blotting, which were consistent with LC-MS. CONCLUSION: There are significant differences of protein profile in the umbilical vein blood plasma between normal and GDM patients with obese offspring. The results indicate that a variety of proteins and biological mechanisms may contribute to childhood obesity. PMID- 27381808 TI - Extended foot-ankle musculoskeletal models for application in movement analysis. AB - Multibody simulations of human motion require representative models of the anatomical structures. A model that captures the complexity of the foot is still lacking. In the present work, two detailed 3D multibody foot-ankle models generated based on CT scans using a semi-automatic tool are described. The proposed models consists of five rigid segments (talus, calcaneus, midfoot, forefoot and toes), connected by five joints (ankle, subtalar, midtarsal, tarsometatarsal and metatarsophalangeal), one with 15DOF and the other with 8DOF. The calculated kinematics of both models were evaluated using gait trials and compared against literature, both presenting realistic results. An inverse dynamic analysis was performed for the 8DOF model, again presenting feasible dynamic results. PMID- 27381807 TI - Time course of peri-implant bone regeneration around loaded and unloaded implants in a rat model. AB - The time-course of cancellous bone regeneration surrounding mechanically loaded implants affects implant fixation, and is relevant to determining optimal rehabilitation protocols following orthopaedic surgeries. We investigated the influence of controlled mechanical loading of titanium-coated polyether-ether ketone (PEEK) implants on osseointegration using time-lapsed, non-invasive, in vivo micro-computed tomography (micro-CT) scans. Implants were inserted into proximal tibial metaphyses of both limbs of eight female Sprague-Dawley rats. External cyclic loading (60 or 100 MUm displacement, 1 Hz, 60 s) was applied every other day for 14 days to one implant in each rat, while implants in contralateral limbs served as the unloaded controls. Hind limbs were imaged with high-resolution micro-CT (12.5 MUm voxel size) at 2, 5, 9, and 12 days post surgery. Trabecular changes over time were detected by 3D image registration allowing for measurements of bone-formation rate (BFR) and bone-resorption rate (BRR). At day 9, mean %BV/TV for loaded and unloaded limbs were 35.5 +/- 10.0% and 37.2 +/- 10.0%, respectively, and demonstrated significant increases in bone volume compared to day 2. BRR increased significantly after day 9. No significant differences between bone volumes, BFR, and BRR were detected due to implant loading. Although not reaching significance (p = 0.16), an average 119% increase in pull-out strength was measured in the loaded implants. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:997-1006, 2017. PMID- 27381810 TI - Controlled moderate hypovolaemia in healthy volunteers is not associated with the development of oxidative stress assessed by plasma F2-isoprostanes and isofurans. AB - Hypovolaemia can be associated with substantial morbidity, particularly when it occurs in the setting of trauma and in patients with comorbid diseases. Hypovolaemia and inflammation such as occur in the setting of trauma and surgery, are associated with systemic oxidative stress and free-radical injury. Free radical injury that results from hypovolaemia-induced organ reperfusion may further augment inflammatory processes. It is unknown exactly what proportion of free-radical injury is associated with isolated hypovolaemia as opposed to the contribution from inflammation from surgery or trauma. In the first human study of its kind, we exposed 8 adult male volunteers to venesection-induced hypovolaemia in progressive aliquots of 5% of total blood volume until 20% had been removed. This blood was subsequently reinfused. Plasma F2-isoprostanes and isofurans, markers of in vivo lipid oxidation, were measured by gas chromatography-mass spectrometry at each 5% aliquot venesected and at each 5% reinfused. Between baseline and maximal blood loss there was a minor fall in haemoglobin concentration from 143.9g/l to 138.8g/l (p=0.004, 95% CI 2.2, 8.0g/L). No significant change from baseline occurred in the concentrations of either plasma F2-isoprostanes or isofurans during venesection (p=0.116 and p=0.152, respectively) or blood reinfusion (p=0.553 and p=0.736, respectively). We can conclude that in healthy adult volunteers, isolated hypovolaemia to 20% total blood volume loss is not associated with detectable systemic oxidative stress. The free-radical injury identified in surgical and trauma patients may represent the effects of tissue damage and inflammation, with an uncertain contribution from tissue ischemia as may occur with hypovolaemia. PMID- 27381809 TI - Proposal of Helicobacter canicola sp. nov., previously identified as Helicobacter cinaedi, isolated from canines. AB - During the course of our taxonomic investigation of Helicobacter cinaedi, it was realized that the strains isolated from dogs, which have been identified as H. cinaedi, showed different biochemical traits than did the isolates obtained from humans. None of the three dog isolates could reduce nitrate to nitrite, whereas all of the human H. cinaedi isolates could do so. The dog isolates showed a strong positive alkaline phosphatase reaction and could grow at 42 degrees C, however the human isolates showed negative to very weak responses to those tests. The GyrA protein based phylogenetic analysis showed that the three isolates from dogs formed a slightly distinct cluster from the human isolate cluster. Phylogenetic analysis of the 16S rRNA, 23S rRNA, gyrB, and hsp60 gene sequences further confirmed that the dog isolates differed from the human H. cinaedi isolate cluster. The whole-genome in silico DNA similarities of each isolate based on their full genome sequences revealed that the isolates from dogs shared more than 94.9% ANIb (average nucleotide identity based on BLAST), while 94.0% ANIb were found between the isolates from dogs and the humans, including the H. cinaedi type strain ATCC BAA-847(T) (=CCUG 18818(T)). From these data, we propose a new species, 'H. canicola' sp. nov., for the isolates from dogs. The type strain is PAGU 1410(T) (CCUG 33887(T)=LMG 29580(T)). PMID- 27381811 TI - Ionic liquid coated copper wires and tubes for fiber-in-tube solid-phase microextraction. AB - A fiber-in-tube solid-phase microextraction (SPME) device was developed by filling eleven copper wires into a copper tube, and all of those were functionalized with ionic liquids. Its morphology and surface properties were characterized by scanning electron microscopy. It was connected into high performance liquid chromatography (HPLC) equipment by replacing the sample loop of six-port injection valve, building the online SPME-HPLC system. In the optimization of extraction conditions, sampling rate, sample volume, pH of sample and desorption time were investigated with five estrogens as model analytes. Under the optimum conditions, an online SPME-HPLC analysis method was achieved, showing enrichment efficiency from 611 to 1661 and a good linearity of 0.06 60MUgL(-1) with low detection limits of 0.02-0.05MUgL(-1). It was applied to detect estrogens analytes in two water samples, with recoveries in the range of 85-114%. Relative standard deviation (n=3) of extraction repeatability is in the range of 1.9-3.0%. Relative standard deviation of extraction tubes (n=3) is in the range of 12-19%. The extraction mechanism is probably related to hydrophobic, pi-pi and dipole-dipole interactions between ionic liquids coating and estrogens analytes. PMID- 27381812 TI - Regulation of Schwann cell proliferation and migration by miR-1 targeting brain derived neurotrophic factor after peripheral nerve injury. AB - Peripheral nerve injury is a global problem that causes disability and severe socioeconomic burden. Brain-derived neurotrophic factor (BDNF) benefits peripheral nerve regeneration and becomes a promising therapeutic molecule. In the current study, we found that microRNA-1 (miR-1) directly targeted BDNF by binding to its 3'-UTR and caused both mRNA degradation and translation suppression of BDNF. Moreover, miR-1 induced BDNF mRNA degradation primarily through binding to target site 3 rather than target site 1 or 2 of BDNF 3'-UTR. Following rat sciatic nerve injury, a rough inverse correlation was observed between temporal expression profiles of miR-1 and BDNF in the injured nerve. The overexpression or silencing of miR-1 in cultured Schwann cells (SCs) inhibited or enhanced BDNF secretion from the cells, respectively, and also suppressed or promoted SC proliferation and migration, respectively. Interestingly, BDNF knockdown could attenuate the enhancing effect of miR-1 inhibitor on SC proliferation and migration. These findings will contribute to the development of a novel therapeutic strategy for peripheral nerve injury, which overcomes the limitations of direct administration of exogenous BDNF by using miR-1 to regulate endogenous BDNF expression. PMID- 27381813 TI - Microfluidics in the selection of affinity reagents for the detection of cancer: paving a way towards future diagnostics. AB - Microfluidic technologies have miniaturized a variety of biomedical applications, and these chip-based systems have several significant advantages over their large scale counterparts. Recently, this technology has been used for automating labor intensive and time-consuming screening processes, whereby affinity reagents, including aptamers, peptides, antibodies, polysaccharides, glycoproteins, and a variety of small molecules, are used to probe for molecular biomarkers. When compared to conventional methods, the microfluidic approaches are faster, more compact, require considerably smaller quantities of samples and reagents, and can be automated. Furthermore, they allow for more precise control of reaction conditions (e.g., pH, temperature, and shearing forces) such that more efficient screening can be performed. A variety of affinity reagents for targeting cancer cells or cancer biomarkers are now available and will likely replace conventional antibodies. In this review article, the selection of affinity reagents for cancer cells or cancer biomarkers on microfluidic platforms is reviewed with the aim of highlighting the utility of such approaches in cancer diagnostics. PMID- 27381814 TI - Selective enamel etching in cervical lesions for self-etch adhesives: A systematic review and meta-analysis. AB - OBJECTIVES: To identify if selective etching of enamel (SEE) margins improves the retention rates and marginal discoloration of cervical composite restorations in non-carious cervical lesions (NCCLs) of adult patients. SOURCE: MEDLINE, Scopus, Web of Science, LILACS, BBO Library, Cochrane Library and SIGLE were searched without restrictions, as well as IADR abstracts and gray literature via trial registries. Dissertations and theses were searched using the ProQuest Dissertations and Periodicos Capes Theses databases. STUDY SELECTION: We included randomized clinical trials that compared the clinical effectiveness of SEE using the self-etch adhesive for direct composite resin restorations in NCCLs in the permanent dentition. DATA: After removal of duplicates, 2689 articles were identified. Following screening of abstracts, 10 studies remained in the qualitative synthesis. Seven were considered to be at "low" risk of bias. The report of the studies varied from 1 to 5 years. Except for one-year follow-up, there was a significantly lower marginal discoloration and marginal adaptation during all follow-up periods. Significantly less loss of retention of restorations at the 3-year follow-up was observed with the selective enamel etching technique. CONCLUSIONS: Selective enamel prior to application of self etch adhesive systems in NCCLs might improve clinical performance of resin composite cervical restorations, although further long-term research is required to confirm this. CLINICAL SIGNIFICANCE: Selective enamel etching prior to application of self-etch adhesive systems in NCCLs can produce composite restorations with higher longevity. PMID- 27381815 TI - Site-selective incorporation and ligation of protein aldehydes. AB - The incorporation of aldehyde handles into proteins, and subsequent chemical reactions thereof, is rapidly proving to be an effective way of generating homogeneous, covalently linked protein constructs that can display a vast array of functionality. In this review, we discuss methods for introducing aldehydes into target proteins, and summarise the ligation strategies for site-selective modification of proteins containing this class of functional handles. PMID- 27381816 TI - Bicarbonate and mannitol treatment for traumatic rhabdomyolysis revisited. AB - BACKGROUND: A rhabdomyolysis protocol (RP) with mannitol and bicarbonate to prevent acute renal dysfunction (ARD, creatinine >2.0 mg/dL) remains controversial. METHODS: Patients with creatine kinase (CK) greater than 2,000 U/L over a 10-year period were identified. Shock, Injury Severity Score, massive transfusion, intravenous contrast exposure, and RP use were evaluated. RP was initiated for a CK greater than 10,000 U/L (first half of the study) or greater than 20,000 U/L (second half). Multivariable analyses were used to identify predictors of ARD and the independent effect of the RP. RESULTS: Seventy-seven patients were identified, 24 (31%) developed ARD, and 4 (5%) required hemodialysis. After controlling for other risk factors, peak CK greater than 10,000 U/L (odds ratio 8.6, P = .016) and failure to implement RP (odds ratio 5.7, P = .030) were independent predictors of ARD. Among patients with CK greater than 10,000, ARD developed in 26% of patients with the RP versus 70% without it (P = .008). CONCLUSION: Reduced ARD was noted with RP. A prospective controlled study is still warranted. PMID- 27381818 TI - Let us discuss how cascading can help implement the circular economy and the bio economy strategies. PMID- 27381817 TI - Interhospital transfer for acute surgical care: does delay matter? AB - BACKGROUND: Delays to definitive care are associated with poor outcomes after trauma and medical emergencies. It is unknown whether inter-hospital transfer delays affect outcomes for nontraumatic acute surgical conditions. METHODS: We performed a retrospective cohort study of patient transfers for acute surgical conditions within a regional transfer network from 2009 to 2013. Delay was defined as more than 24 hours from presentation to transfer request and categorized as 1 or 2+ days. The primary outcome was post-transfer death or hospice. Bivariate and multivariable logistic regression were performed. RESULTS: The cohort included 2,091 patient transfers. Delays of 2 or more days were associated with death or hospice in unadjusted analyses, but there was no difference after adjustment. Predictors of post-transfer death or hospice included older age, higher comorbidity scores, and greater severity of illness. CONCLUSIONS: Delays in transfer request were not associated with post-transfer mortality or discharge to hospice, suggesting effective triage of nontraumatic acute surgical patients. PMID- 27381819 TI - Copper-Catalyzed Transformations Using Cu-H, Cu-B, and Cu-Si as Active Catalyst Species. AB - This review summarizes transformations using copper hydride (Cu-H), boryl copper (Cu-B) or silyl copper (Cu-Si) as active catalyst species. Semihydrogenation, hydroboration, and hydrocarboxylation have been developed using Cu-H as active catalyst species. Preferential reduction of sterically hindered ketones is accompanied by Cu-H species bearing a bowl-shaped phosphine as a crucial ligand. Employing Cu-B species, hydroboration of alkynes and allenes, synthesis of 2 boryl-1,3-butadiene, and borylative allyl-allyl coupling are established. Silacarboxylation of alkynes, regiodivergent silacarboxylation of allenes, and silylative allylation of ketones involve Cu-Si species. The key to these selective transformations is regioselective addition of Cu-H, Cu-B, or Cu-Si species to carbon-carbon multiple bonds of alkynes and allenes to afford the corresponding alkenylcopper or allylcopper intermediates. PMID- 27381820 TI - Human biliary tree stem/progenitor cells immunomodulation: Role of hepatocyte growth factor. AB - AIM: Human biliary tree stem/progenitor cells (hBTSC) are multipotent epithelial stem cells with the potential for allogenic transplant in liver, biliary tree, and pancreatic diseases. Human mesenchymal stem cells, but also epithelial stem cells, are able to modulate immune responses with different types of secretion molecules. METHODS: The initial aim of the present study was to develop for the first time a culture protocol in order to expand hBTSC in vitro through passages, allowing to maintain a similar stem cell and secretome profile. Furthermore, we investigated the secretome profile of the hBTSC to assess the production of molecules capable of affecting immune feedback. RESULTS: We found that hepatocyte growth factor produced by hBTSC exerts its cytoprotective role inducing apoptosis in human immune cells, such as lymphocytes. CONCLUSIONS: The present study, therefore, supports the hypothesis that hBTSC can be useful for the purpose of regenerative medicine, as they can be banked and expanded, and they can secrete immunoregulatory factors. PMID- 27381821 TI - Sedation and anaesthesia for non-obstetric surgery. PMID- 27381822 TI - Altered resting-state neural activity and changes following a craving behavioral intervention for Internet gaming disorder. AB - Internet gaming disorder (IGD) has become a serious mental health issue worldwide. Evaluating the benefits of interventions for IGD is of great significance. Thirty-six young adults with IGD and 19 healthy comparison (HC) subjects were recruited and underwent resting-state fMRI scanning. Twenty IGD subjects participated in a group craving behavioral intervention (CBI) and were scanned before and after the intervention. The remaining 16 IGD subjects did not receive an intervention. The results showed that IGD subjects showed decreased amplitude of low fluctuation in the orbital frontal cortex and posterior cingulate cortex, and exhibited increased resting-state functional connectivity between the posterior cingulate cortex and dorsolateral prefrontal cortex, compared with HC subjects. Compared with IGD subjects who did not receive the intervention, those receiving CBI demonstrated significantly reduced resting state functional connectivity between the: (1) orbital frontal cortex with hippocampus/parahippocampal gyrus; and, (2) posterior cingulate cortex with supplementary motor area, precentral gyrus, and postcentral gyrus. These findings suggest that IGD is associated with abnormal resting-state neural activity in reward-related, default mode and executive control networks. Thus, the CBI may exert effects by reducing interactions between regions within a reward-related network, and across the default mode and executive control networks. PMID- 27381823 TI - Embryonic lethal abnormal vision proteins and adenine and uridine-rich element mRNAs after global cerebral ischemia and reperfusion in the rat. AB - Prolonged translation arrest correlates with delayed neuronal death of hippocampal CA1 neurons following global cerebral ischemia and reperfusion. Many previous studies investigated ribosome molecular biology, but mRNA regulatory mechanisms after brain ischemia have been less studied. Here we investigated the embryonic lethal abnormal vision/Hu isoforms HuR, HuB, HuC, and HuD, as well as expression of mRNAs containing adenine and rich uridine elements following global ischemia in rat brain. Proteomics of embryonic lethal abnormal vision immunoprecipitations or polysomes isolated from rat hippocampal CA1 and CA3 from controls or following 10 min ischemia plus 8 h of reperfusion showed distinct sets of mRNA-binding proteins, suggesting differential mRNA regulation in each condition. Notably, HuB, HuC, and HuD were undetectable in NIC CA1. At 8 h reperfusion, polysome-associated mRNAs contained 46.1% of ischemia-upregulated mRNAs containing adenine and rich uridine elements in CA3, but only 18.7% in CA1. Since mRNAs containing adenine and rich uridine elements regulation are important to several cellular stress responses, our results suggest CA1 is disadvantaged compared to CA3 in coping with ischemic stress, and this is expected to be an important contributing factor to CA1 selective vulnerability. (Data are available via ProteomeXchange identifier PXD004078 and GEO Series accession number GSE82146). PMID- 27381824 TI - Quantitative longitudinal imaging of activated microglia as a marker of inflammation in the pilocarpine rat model of epilepsy using [11C]-( R)-PK11195 PET and MRI. AB - Inflammation may play a role in the development of epilepsy after brain insults. [11C]-( R)-PK11195 binds to TSPO, expressed by activated microglia. We quantified [11C]-( R)-PK11195 binding during epileptogenesis after pilocarpine-induced status epilepticus (SE), a model of temporal lobe epilepsy. Nine male rats were studied thrice (D0-1, D0 + 6, D0 + 35, D0 = SE induction). In the same session, 7T T2-weighted images and DTI for mean diffusivity (MD) and fractional anisotropy (FA) maps were acquired, followed by dynamic PET/CT. On D0 + 35, femoral arterial blood was sampled for rat-specific metabolite-corrected arterial plasma input functions (AIFs). In multiple MR-derived ROIs, we assessed four kinetic models (two with AIFs; two using a reference region), standard uptake values (SUVs), and a model with a mean AIF. All models showed large (up to two-fold) and significant TSPO binding increases in regions expected to be affected, and comparatively little change in the brainstem, at D0 + 6. Some individuals showed increases at D0 + 35. AIF models yielded more consistent increases at D0 + 6. FA values were decreased at D0 + 6 and had recovered by D0 + 35. MD was increased at D0 + 6 and more so at D0 + 35. [11C]-( R)-PK11195 PET binding and MR biomarker changes could be detected with only nine rats, highlighting the potential of longitudinal imaging studies. PMID- 27381825 TI - Sestrin2, as a negative feedback regulator of mTOR, provides neuroprotection by activation AMPK phosphorylation in neonatal hypoxic-ischemic encephalopathy in rat pups. AB - Hypoxic-ischemic encephalopathy is a condition caused by reduced oxygen and cerebral blood flow to the brain resulting in neurological impairments. Effective therapeutic treatments to ameliorate these disabilities are still lacking. We sought to investigate the role of sestrin2, a highly conserved stress-inducible protein, in a neonatal rat hypoxic-ischemic encephalopathy model. Ten-day-old rat pups underwent right common carotid artery ligation followed by 2.5 h hypoxia. At 1 h post hypoxic-ischemic encephalopathy, rats were intranasally administered with recombinant human sestrin2 and sacrificed for brain infarct area measurement, Fluoro-Jade C, immunofluorescence staining, Western blot, and neurological function testing. rh-sestrin2 reduced brain infarct area, brain atrophy, apoptosis, ventricular area enlargement, and improved neurological function. Western blot showed that sestrin2 expression levels were increased after treatment with rh-sestrin2, and sestrin2 exerts neuroprotective effects via activation of the adenosine monophosphate-activated protein kinase pathway which in turn inhibits mammalian target of rapamycin signaling resulting in the attenuation of apoptosis. In conclusions: Sestrin2 plays an important neuroprotective role after hypoxic-ischemic encephalopathy via adenosine monophosphate-activated protein kinase signaling pathway and serves as a negative feedback regulator of mammalian target of rapamycin. Administration of rh sestrin2 not only reduced infarct area and brain atrophy, but also significantly improved neurological function. PMID- 27381826 TI - Augmentation of poly(ADP-ribose) polymerase-dependent neuronal cell death by acidosis. AB - Tissue acidosis is a key component of cerebral ischemic injury, but its influence on cell death signaling pathways is not well defined. One such pathway is parthanatos, in which oxidative damage to DNA results in activation of poly(ADP ribose) polymerase and generation of poly(ADP-ribose) polymers that trigger release of mitochondrial apoptosis-inducing factor. In primary neuronal cultures, we first investigated whether acidosis per se is capable of augmenting parthanatos signaling initiated pharmacologically with the DNA alkylating agent, N-methyl- N'-nitro- N-nitrosoguanidine. Exposure of neurons to medium at pH 6.2 for 4 h after N-methyl- N'-nitro- N-nitrosoguanidine washout increased intracellular calcium and augmented the N-methyl- N'-nitro- N-nitrosoguanidine evoked increase in poly(ADP-ribose) polymers, nuclear apoptosis-inducing factor , and cell death. The augmented nuclear apoptosis-inducing factor and cell death were blocked by the acid-sensitive ion channel-1a inhibitor, psalmotoxin. In vivo, acute hyperglycemia during transient focal cerebral ischemia augmented tissue acidosis, poly(ADP-ribose) polymers formation, and nuclear apoptosis inducing factor , which was attenuated by a poly(ADP-ribose) polymerase inhibitor. Infarct volume from hyperglycemic ischemia was decreased in poly(ADP ribose) polymerase 1-null mice. Collectively, these results demonstrate that acidosis can directly amplify neuronal parthanatos in the absence of ischemia through acid-sensitive ion channel-1a . The results further support parthanatos as one of the mechanisms by which ischemia-associated tissue acidosis augments cell death. PMID- 27381827 TI - Autocrine release of angiopoietin-2 mediates cerebrovascular disintegration in Moyamoya disease. AB - Moyamoya disease is a rare steno-occlusive cerebrovascular disorder often resulting in hemorrhagic and ischemic strokes. Although sharing the same ischemic stimulus with atherosclerotic cerebrovascular disease, Moyamoya disease is characterized by a highly instable cerebrovascular system which is prone to rupture due to pathological neovascularization. To understand the molecular mechanisms underlying this instability, angiopoietin-2 gene expression was analyzed in middle cerebral artery lesions obtained from Moyamoya disease and atherosclerotic cerebrovascular disease patients. Angiopoietin-2 was significantly up-regulated in Moyamoya vessels, while serum concentrations of soluble angiopoietins were not changed. For further evaluations, cerebral endothelial cells incubated with serum from these patients in vitro were applied. In contrast to atherosclerotic cerebrovascular disease serum, Moyamoya disease serum induced an angiopoietin-2 overexpression and secretion, accompanied by loss of endothelial integrity. These effects were absent or inverse in endothelial cells of non-brain origin suggesting brain endothelium specificity. The destabilizing effects on brain endothelial cells to Moyamoya disease serum were partially suppressed by the inhibition of angiopoietin-2. Our findings define brain endothelial cells as the potential source of vessel-destabilizing factors inducing the high plasticity state and disintegration in Moyamoya disease in an autocrine manner. We also provide new insights into Moyamoya disease pathophysiology that may be helpful for preventive treatment strategies in future. PMID- 27381828 TI - Spreading depolarization triggered by elevated potassium is weak or absent in the rodent lower brain. AB - We examined in live coronal slices from rat and mouse which brain regions generate potassium-triggered spreading depolarization (SDKt). This technique simulates cortical spreading depression, which underlies migraine aura in the intact brain. An SDKt episode was evoked by increasing bath [K+]o and recorded as a propagating front of elevated light transmittance representing transient neuronal swelling in gray matter of neocortex, hippocampus, striatum, and thalamus. In contrast, SDKt was not imaged in hypothalamic nuclei or brainstem with exception of those nuclei near the dorsal brainstem surface. In rat slices, single neurons were whole-cell current clamped during SDKt. "Higher" neurons depolarized to near zero millivolts indicating SDKt generation. In contrast, seven types of neurons in hypothalamus and brainstem only slowly depolarized without generating SDKt, supporting our imaging findings. Therefore, SDKt is not a default of CNS neurons but rather displays a region-specific susceptibility, similar to anoxic depolarization, which we have proposed is correlated with a region's vulnerability to traumatic brain injury. In the higher brain, SDKt may be a vestigial spreading depolarization that originally evolved to shut down and vasoconstrict gray matter regions more exposed to impact and contusion. PMID- 27381830 TI - Pre-diagnostic leukocyte mitochondrial DNA copy number and skin cancer risk. AB - No previous study has examined the association between mitochondrial DNA copy number (mtCN) and skin cancer risk prospectively. We examined the associations between peripheral blood leukocytes mtCN level and the risks of skin cancers in a case-control study nested within the Nurses' Health Study of non-Hispanic White women, including 272 melanoma cases and 293 controls, 508 squamous cell carcinoma (SCC) cases and 550 controls, and 515 basal cell carcinoma (BCC) cases and 536 controls. Relative mtCN in peripheral blood leukocytes was measured by quantitative PCR-based assay. Unconditional logistic regression models were used to examine the associations between mtCN and skin cancer risks. Compared with those with high mtCN, the risk for melanoma was 1.06 [95% confidence interval (CI) = 0.70-1.62] in the median group and 1.19 (95% CI = 0.78-1.81) for the low group. There was suggestive evidence that increased risk for melanoma was apparent among low constitutional susceptibility group [odds ratio (OR)low versus high = 1.80, 95% CI = 0.95-3.39, P for trend = 0.07, P for interaction = 0.06]. The increased risk of melanoma was also apparent among high cumulative UV exposure group (ORlow versus high = 3.40, 95% CI = 1.46-7.92, P for trend = 0.004, P for interaction = 0.01). For non-melanoma skin cancers, compared with high-mtCN group, low-mtCN group had an increased risk for SCC (OR = 1.26, 95% CI = 0.93-1.71) and BCC (OR = 1.35; 95% CI = 1.00-1.82). Because some of the associations were marginally significant, the results only provided suggestive evidence. Further studies are warranted to replicate these findings and better understand the underlying mechanisms. PMID- 27381829 TI - K-Ras and cyclooxygenase-2 coactivation augments intraductal papillary mucinous neoplasm and Notch1 mimicking human pancreas lesions. AB - Mutational activation of K-Ras is an initiating event of pancreatic ductal adenocarcinomas (PDAC) that may develop either from pancreatic intraepithelial neoplasia (PanIN) or intraductal papillary mucinous neoplasms (IPMN). Cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) is causally related to pancreatic carcinogenesis. Here, we deciphered the impact of COX-2, a key modulator of inflammation, in concert with active mutant K-Ras(G12D) on tumor burden and gene expression signature using compound mutant mouse lines. Concomitant activation of COX-2 and K-Ras(G12D) accelerated the progression of pancreatic intraepithelial lesions predominantly with a cystic papillary phenotype resembling human IPMN. Transcriptomes derived from laser capture microdissected preneoplastic lesions of single and compound mutants revealed a signature that was significantly enriched in Notch1 signaling components. In vitro, Notch1 signaling was COX-2-dependent. In line with these findings, human IPMN stratified into intestinal, gastric and pancreatobillary types displayed Notch1 immunosignals with high prevalence, especially in the gastric lesions. In conclusion, a yet unknown link between activated Ras, protumorigenic COX-2 and Notch1 in IPMN onset was unraveled. PMID- 27381831 TI - Sequence variation in mature microRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients. AB - Single nucleotide polymorphisms (SNPs) in microRNA genes have been associated with colorectal cancer (CRC) risk, survival and response to treatment. Conflicting results are available on the association between rs4919510, a SNP in mature miR-608 and clinical outcome in CRC. Here, we analyzed the association between rs4919510 and benefit from perioperative treatment in a randomised phase II trial of neoadjuvant Capecitabine and Oxaliplatin (CAPOX) followed by chemo radiotherapy, surgery and adjuvant CAPOX +/- Cetuximab in high-risk locally advanced rectal cancer (LARC). A total of 155/164 (94.5%) patients were assessable. 95 (61.3%) were homozygous for CC, 55 (35.5%) heterozygous (CG) and 5 (3.2%) homozygous for GG. Median follow-up was 64.9 months. In the CAPOX arm the 5-year progression-free survival (PFS) and overall survival (OS) rates were 54.6% and 60.7% for CC and 82.0% and 82.1% for CG/GG, respectively (HR PFS 0.13, 95% CI: 0.12-0.83, P = 0.02; HR OS 0.38, 95% CI: 0.14-1.01, P = 0.05). In the CAPOX-C arm PFS and OS were 73.2 and 82.2%, respectively for CC carriers and 64.6 and 73.1% for CG/GG carriers (HR PFS 1.38, 95% CI: 0.61-3.13, P = 0.44; HR OS 1.34, 95% CI: 0.52-3.48, P = 0.55). An interaction was found between study treatment and rs4919510 genotype for both PFS (P = 0.02) and OS (P = 0.07). This is the first study investigating rs4919510 in LARC. The CC genotype appeared to be associated with worse prognosis compared to the CG/GG genotype in patients treated with chemotherapy and chemo-radiotherapy alone. Addition of Cetuximab to chemotherapy and chemo-radiotherapy in CC carriers appeared to improve clinical outcome. PMID- 27381833 TI - Spatial and temporal investigation of the microbiome of the Caribbean octocoral Erythropodium caribaeorum. AB - The octocoral Erythropodium caribaeorum is an important species in the Caribbean coral reef community and a source of the cytotoxic natural product desmethyleleutherobin. We utilized 16S small subunit rRNA gene amplicon pyrosequencing to characterize the microbiome of E. caribaeorum collected from Florida, USA and San Salvador, The Bahamas at multiple time points. This coral was found to have a very high microbial richness with an average Chao1 estimated richness of 1464 +/- 707 operational taxonomic units and average Shannon diversity index of 4.26 +/- 1.65. The taxonomic class Gammaproteobacteria was a dominant member in all samples and the genus Endozoicomonas accounted for an average of 37.7% +/- 30.0% of the total sequence reads. One Endozoicomonas sp. was found to be a stable member of all E. caribaeorum sequence libraries regardless of location or time of collection and accounted for 30.1% of all sequence reads. This is the first report characterizing the microbiome associated with the encrusting octocoral E. caribaeorum. PMID- 27381832 TI - 3D map of the human corneal endothelial cell. AB - Corneal endothelial cells (CECs) are terminally differentiated cells, specialized in regulating corneal hydration and transparency. They are highly polarized flat cells that separate the cornea from the aqueous humor. Their apical surface, in contact with aqueous humor is hexagonal, whereas their basal surface is irregular. We characterized the structure of human CECs in 3D using confocal microscopy of immunostained whole corneas in which cells and their interrelationships remain intact. Hexagonality of the apical surface was maintained by the interaction between tight junctions and a submembraneous network of actomyosin, braced like a drum. Lateral membranes, which support enzymatic pumps, presented complex expansions resembling interdigitated foot processes at the basal surface. Using computer-aided design and drafting software, we obtained a first simplified 3D model of CECs. By comparing their expression with those in epithelial, stromal and trabecular corneal cells, we selected 9 structural or functional proteins for which 3D patterns were specific to CECs. This first 3D map aids our understanding of the morphologic and functional specificity of CECs and could be used as a reference for characterizing future cell therapy products destined to treat endothelial dysfunctions. PMID- 27381835 TI - Effects of defaunation and dietary coconut oil distillate on fermentation, digesta kinetics and methane production of Brahman heifers. AB - A 2 * 2 factorial experiment was conducted to assess the effects of presence or absence of rumen protozoa and of dietary coconut oil distillate (COD) supplementation on rumen fermentation characteristics, digesta kinetics and methane production in Brahman heifers. Twelve Brahman heifers were selected to defaunate, with 6 being subsequently refaunated. After defaunation and refaunation, heifers were randomly allocated to COD supplement or no supplement treatments while fed an oaten chaff-based diet. Methane production (MP; 94.17 v 104.72 g CH4 /d) and methane yield [MY; 19.45 v 21.64 g CH4 /kg dry matter intake (DMI)] were reduced in defaunated heifers compared with refaunated heifers when measured at 5 weeks after refaunation treatment (p < 0.01). Supplement of COD similarly reduced MP and MY (89.36 v 109.53 g/d and 18.46 v 22.63 g/kg DMI, respectively; p < 0.01), and there were no significant interactions of defaunation and COD effects on rumen fermentation or methane emissions. Concentration of total volatile fatty acid (VFA) and molar proportions of acetate, propionate and butyrate was not affected by defaunation or by COD. Microbial crude protein (MCP; g/d) outflow was increased by defaunation (p < 0.01) in the absence of COD but was unaffected by defaunation in COD-supplemented heifers. There was a tendency towards a greater average daily gain (ADG) in defaunated heifers (p = 0.09), but COD did not increase ADG (p > 0.05). The results confirmed that defaunation and COD independently reduced enteric MP even though the reduced emissions were achieved without altering rumen fermentation VFA levels or gut digesta kinetics. PMID- 27381834 TI - Improved antifouling properties and selective biofunctionalization of stainless steel by employing heterobifunctional silane-polyethylene glycol overlayers and avidin-biotin technology. AB - A straightforward solution-based method to modify the biofunctionality of stainless steel (SS) using heterobifunctional silane-polyethylene glycol (silane PEG) overlayers is reported. Reduced nonspecific biofouling of both proteins and bacteria onto SS and further selective biofunctionalization of the modified surface were achieved. According to photoelectron spectroscopy analyses, the silane-PEGs formed less than 10 A thick overlayers with close to 90% surface coverage and reproducible chemical compositions. Consequently, the surfaces also became more hydrophilic, and the observed non-specific biofouling of proteins was reduced by approximately 70%. In addition, the attachment of E. coli was reduced by more than 65%. Moreover, the potential of the overlayer to be further modified was demonstrated by successfully coupling biotinylated alkaline phosphatase (bAP) to a silane-PEG-biotin overlayer via avidin-biotin bridges. The activity of the immobilized enzyme was shown to be well preserved without compromising the achieved antifouling properties. Overall, the simple solution-based approach enables the tailoring of SS to enhance its activity for biomedical and biotechnological applications. PMID- 27381837 TI - Arterial stiffness in obstructive sleep apnoea: Is there a difference between daytime and night-time? AB - BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea syndrome (OSAS) is a common chronic systemic disease in the general population, with known associated cardiovascular outcomes. We aimed to investigate arterial stiffness in OSAS patients and compare daytime and night-time values with control subjects. METHODS: A total of 104 patients undergoing investigation for OSAS with polysomnography also underwent pulse wave velocity (PWV) and augmentation index (AIx) measurements with Mobil-O-Graph for 24 h. Eighty-two patients were found to have OSAS and 22 did not have OSAS and acted as controls. RESULTS: PWV values of the 82 OSAS patients during the 24-h period, both daytime and night-time, were significantly higher than that of the control subjects. Moreover, night-time levels of AIx were significantly higher in OSAS patients than control subjects (P = 0.025). PWV during night-time was higher than daytime measurements in OSAS patients (P = 0.012). Apnoea hypopnoea index (AHI) was significantly correlated with PWV and AIx over 24 h (P = 0.0001, r = 0.412; P = 0.002, r = 0.333, respectively). Positive correlations were also found between oxygen desaturation index (ODI) with PWV and AIx during the night (P = 0.0001, r = 0.480; P = 0.002, r = 0.325, respectively). However, daytime AIx was not significantly correlated with ODI (P = 0.052, r = 0.205). CONCLUSION: OSAS patients, without known cardiovascular disease, have increased PWV, indicating an increased arterial stiffness, compared with control subjects and correlations between AHI and arterial stiffness indices suggest increased arterial stiffness with increased disease severity. Therefore, arterial stiffness should be considered as a possible cause for cardiovascular complications in OSAS patients. PMID- 27381838 TI - Faces in Context: Does Face Perception Depend on the Orientation of the Visual Scene? AB - The mechanisms held responsible for familiar face recognition are thought to be orientation dependent; inverted faces are more difficult to recognize than their upright counterparts. Although this effect of inversion has been investigated extensively, researchers have typically sliced faces from photographs and presented them in isolation. As such, it is not known whether the perceived orientation of a face is inherited from the visual scene in which it appears. Here, we address this question by measuring performance in a simultaneous same different task while manipulating both the orientation of the faces and the scene. We found that the face inversion effect survived scene inversion. Nonetheless, an improvement in performance when the scene was upside down suggests that sensitivity to identity increased when the faces were more easily segmented from the scene. Thus, while these data identify congruency with the visual environment as a contributing factor in recognition performance, they imply different mechanisms operate on upright and inverted faces. PMID- 27381836 TI - Roles of Supplementary Motor Areas in Auditory Processing and Auditory Imagery. AB - Although the supplementary and pre-supplementary motor areas have been intensely investigated in relation to their motor functions, they are also consistently reported in studies of auditory processing and auditory imagery. This involvement is commonly overlooked, in contrast to lateral premotor and inferior prefrontal areas. We argue here for the engagement of supplementary motor areas across a variety of sound categories, including speech, vocalizations, and music, and we discuss how our understanding of auditory processes in these regions relate to findings and hypotheses from the motor literature. We suggest that supplementary and pre-supplementary motor areas play a role in facilitating spontaneous motor responses to sound, and in supporting a flexible engagement of sensorimotor processes to enable imagery and to guide auditory perception. PMID- 27381839 TI - Relapse of pemphigus vulgaris after topical application of ingenol mebutate. AB - Ingenol mebutate is a recently approved topical agent for the treatment of actinic keratosis. Its most common adverse effects are transient local skin reactions. We report a 63-year-old white man who presented with a red-brownish crusted plaque involving the dorsum of his nose and an eroded area on his lower lip, which appeared soon after topical application of ingenol mebutate gel. Clinical, histological and immunopathological features were consistent with a diagnosis of pemphigus vulgaris (PV). To our knowledge, this is the first report of relapse of PV after topical application of ingenol mebutate gel. The temporal relationship between the application of the drug and the outbreak of PV supports the involvement of this agent in triggering the disease. It is plausible that ingenol mebutate may have induced the disease by its action on the production of proinflammatory cytokines. PMID- 27381840 TI - Distribution and self-assisted diffusion of Be and Mg impurities in ZnO. AB - The band gap width of the Be-doped ZnO correlates strongly with the distribution of the dopants. By performing first-principles calculations, it is found that an interstitial Be (Bei) atom preferably migrates in a basal plane. During the migration, such a Bei atom favorably bonds to a substituted Be (BeZn) atom, forming a new defect complex (2Be)Zn, showing a trend of aggregation of Be atoms in ZnO. Furthermore, the stability of the defect complex (2Be)Zn can be weakened by a substituted Mg (MgZn). So, the Mg impurities in Be-doped ZnO might suppress the aggregation of Be, so as to significantly improve the effect of the doped Be on modulating the band gap of ZnO. PMID- 27381841 TI - Surgical repair of multiple congenital left ventricular aneurysms with rupture into left atrium. AB - Congenital left ventricular aneurysm (CLVA) associated with multiple aneurysms with rupture into the left atrium (LA) is rare. We report a 17-year-old male with two CLVAs, one of which ruptured into the LA, and discuss the surgical management and review the literature of this rare disease. PMID- 27381842 TI - Knockdown of gene expression by antisense morpholino oligos in preimplantation mouse embryos cultured in vitro. AB - Knockdown of gene expression by antisense morpholino oligos (MOs) is a simple and effective method for analyzing the roles of genes in mammalian cells. Here, we demonstrate the efficient delivery of MOs by Endo-Porter (EP), a special transfection reagent for MOs, into preimplantation mouse embryos cultured in vitro. A fluorescein-labeled control MO was applied for monitoring the incorporation of MOs into developing 2-cell embryos in the presence of varying amounts of EP and bovine serum albumin. In optimized conditions, fluorescence was detected in 2-cell embryos within a 3-h incubation period. In order to analyze the validity of the optimized conditions, an antisense Oct4 MO was applied for knockdown of the synthesis of OCT4 protein in developing embryos from the 2-cell stage. In blastocysts, the antisense Oct4 MO induced a decrease in the amount in OCT4 protein to less than half. An almost complete absence of OCT4-positive cells and nearly complete disappearance of the inner cell mass in the outgrowths of blastocysts were also noted. These phenotypes corresponded with those of Oct4 deficient mouse embryos. Overall, we suggest that the delivery of MOs using EP is useful for the knockdown of gene expression in preimplantation mouse embryos cultured in vitro. PMID- 27381843 TI - Robert Califf: controversial new head of the FDA. PMID- 27381844 TI - In Primary Aldosteronism, Mineralocorticoids Influence Exosomal Sodium-Chloride Cotransporter Abundance. AB - Distal tubular sodium retention is a potent driver of hypertension, and the thiazide-sensitive sodium-chloride cotransporter (NCC) has a key role in this process. In humans, factors regulating NCC are unclear, but in animal models, aldosterone is a potent regulator, possibly via effects on plasma potassium. We studied the effects of the mineralocorticoid fludrocortisone on the abundance of NCC and its phosphorylated form (pNCC) as well as WNK lysine deficient protein kinase 4 (WNK4) and STE20/SPS1-related, proline alanine-rich kinase (SPAK) in human urinary exosomes. We isolated exosomes from daily urine samples in 25 patients undergoing fludrocortisone suppression testing (100 MUg every 6 hours for 4 days) to diagnose or exclude primary aldosteronism. Over the course of the test, NCC levels increased 3.68-fold (P<0.01) and pNCC levels increased 2.73-fold (P<0.01) relative to baseline. The ratio of pNCC/NCC dropped by 48% (P<0.01). The abundance of WNK4 increased 3.23-fold (P<0.01), but SPAK abundance did not change significantly (P=0.14). Plasma potassium concentration strongly and negatively correlated with pNCC, NCC, and WNK4 abundance (P<0.001 for all). This study shows that, in humans, mineralocorticoid administration is associated with a rapid increase in abundance of NCC and pNCC, possibly via the WNK pathway. These effects may be driven by changes in plasma potassium. PMID- 27381845 TI - Response by Dr. Lapaj to comment on Lapaj et al.: Retrieval analysis of titanium nitride (TiN) coated prosthetic femoral heads articulating with polyethylene. PMID- 27381846 TI - Overexpression of Inhibitor of Growth 4 Enhances Radiosensitivity in Non-Small Cell Lung Cancer Cell Line SPC-A1. AB - Inhibitor of growth 4 is a member of the inhibitor of growth family proteins, which is involved in cell apoptosis, migration, invasion, and cell cycle progress. In this study, we investigated the inhibitor of growth 4 level in non small cell lung cancer tissues and explored the antitumor activity of inhibitor of growth 4 in vitro and in vivo using non-small cell lung cancer cell line SPC A1 and its underlying molecular mechanisms. We also explored its role on the radiosensitivity in SPC-A1 cells. The level of inhibitor of growth 4 protein was significantly decreased in 28 cases of non-small cell lung cancer tissues in comparison with corresponding noncancerous lung epithelial tissues. Upregulation of inhibitor of growth 4 by plasmid pcDNA3.1-ING4 delivery could suppress proliferation and increase apoptosis of SPC-A1 cells both in vitro and in vivo. Additionally, we found that overexpression of inhibitor of growth 4 in SPC-A1 cell line could lead to a higher Bcl-2/Bax ratio, which might be an important factor in the apoptosis regulation. Furthermore, overexpression of inhibitor of growth 4 enhanced the radiosensitivity of SPC-A1 cells to irradiation. Inhibitor of growth 4 upregulation plus radiotherapy induced synergistic tumor suppression in SPC-A1 xenografts implanted in athymic nude mice. Thus, the restoration of inhibitor of growth 4 function might provide a potential strategy for non-small cell lung cancer radiosensitization. PMID- 27381848 TI - When is a GP home-visit program financially viable? AB - Despite a decline in GP home visits in Australia, these services remain an important aspect of healthcare access and delivery for the aged population. Home visits can both provide better care and decrease use of ambulance and emergency department (ED) services. The net costs of providing GP visits are complex, depending on the relative costs of home visits and ED attendances, the number of ED attendances saved by GP visits, and the number of services provided per day by a visiting GP. The Australian Capital Territory government created the General Practice Aged Day Service (GPADS) program in March 2011. Using data and information from this program as a basis, we examine the financial aspects of a daytime home-visit program in the Australian context. Whether or not a program is financially viable depends on a range of parameters; if all factors are aligned a program can generate net savings. While there is no information available on the net health benefits of home visits relative to ED attendance, these differences need not be large for the program to be cost-effective. PMID- 27381847 TI - Label-Free Raman Imaging to Monitor Breast Tumor Signatures. AB - Although not yet ready for clinical application, methods based on Raman spectroscopy have shown significant potential in identifying, characterizing, and discriminating between noncancerous and cancerous specimens. Real-time and accurate medical diagnosis achievable through this vibrational optical method largely benefits from improvements in current technological and software capabilities. Not only is the acquisition of spectral information now possible in milliseconds and analysis of hundreds of thousands of data points achieved in minutes, but Raman spectroscopy also allows simultaneous detection and monitoring of several biological components. Besides demonstrating a significant Raman signature distinction between nontumorigenic (MCF-10A) and tumorigenic (MCF-7) breast epithelial cells, our study demonstrates that Raman can be used as a label free method to evaluate epidermal growth factor activity in tumor cells. Comparative Raman profiles and images of specimens in the presence or absence of epidermal growth factor show important differences in regions attributed to lipid, protein, and nucleic acid vibrations. The occurrence, which is dependent on the presence of epidermal growth factor, of new Raman features associated with the appearance of phosphothreonine and phosphoserine residues reflects a signal transduction from the membrane to the nucleus, with concomitant modification of DNA/RNA structural characteristics. Parallel Western blotting analysis reveals an epidermal growth factor induction of phosphorylated Akt protein, corroborating the Raman results. The analysis presented in this work is an important step toward Raman-based evaluation of biological activity of epidermal growth factor receptors on the surfaces of breast cancer cells. With the ultimate future goal of clinically implementing Raman-guided techniques for the diagnosis of breast tumors (e.g., with regard to specific receptor activity), the current results just lay the foundation for further label-free optical tools to diagnose the disease. PMID- 27381850 TI - An overview of circulating cell-free microRNAs as putative biomarkers in Alzheimer's and Parkinson's Diseases. AB - Circulating cell-free microRNAs (miRNAs) are stable in many biological fluids and their expression profiles can suffer changes under different physiological and pathological conditions. In the last few years, miRNAs have been proposed as putative noninvasive biomarkers in diagnosis, prognosis and response to treatment for several diseases, including neurodegenerative disorders as Alzheimer's disease (AD) and Parkinson's disease (PD). Cognitive and/or motor impairments are usually considered for establishing clinical diagnosis, and at this stage, the majority of the neurons may already be lost making difficult attempts of novel therapies. In this review, we intend to survey the circulating cell-free miRNAs found as dysregulated in cerebrospinal fluid, serum and plasma samples in AD and PD patients, and show how those miRNAs can be useful for early and differential diagnosis. Beyond that, we highlighted the miRNAs that are possibly related to common molecular mechanisms in the neurodegeneration process, as well those miRNAs related to specific disease pathways. PMID- 27381851 TI - Effect of water presence on choline chloride-2urea ionic liquid and coating platings from the hydrated ionic liquid. AB - In the present study, hygroscopicity of the choline chloride-urea (ChCl-2Urea) ionic liquid (IL) was confirmed through Karl-Fisher titration examination, indicating that the water content in the hydrated ChCl-2Urea IL was exposure-time dependent and could be tailored by simple heating treatment. The impact of the absorbed water on the properties of ChCl-2Urea IL, including viscosity, electrical conductivity, electrochemical window and chemical structure was investigated. The results show that water was able to dramatically reduce the viscosity and improve the conductivity, however, a broad electrochemical window could be persisted when the water content was below ~6 wt.%. These characteristics were beneficial for producing dense and compact coatings. Nickel (Ni) coatings plating from hydrated ChCl-2Urea IL, which was selected as an example to show the effect of water on the electroplating, displayed that a compact and corrosion-resistant Ni coating was plated from ChCl-2Urea IL containing 6 wt.% water doped with 400 mg/L NA at a moderate temperature. As verified by FTIR analysis, the intrinsic reason could be ascribed that water was likely linked with urea through strong hydrogen bond so that the water decomposition was suppressed during plating. Present study may provide a reference to prepare some similar water-stable ILs for plating. PMID- 27381849 TI - Genetically modified (GM) crops: milestones and new advances in crop improvement. AB - KEY MESSAGE: New advances in crop genetic engineering can significantly pace up the development of genetically improved varieties with enhanced yield, nutrition and tolerance to biotic and abiotic stresses. Genetically modified (GM) crops can act as powerful complement to the crops produced by laborious and time consuming conventional breeding methods to meet the worldwide demand for quality foods. GM crops can help fight malnutrition due to enhanced yield, nutritional quality and increased resistance to various biotic and abiotic stresses. However, several biosafety issues and public concerns are associated with cultivation of GM crops developed by transgenesis, i.e., introduction of genes from distantly related organism. To meet these concerns, researchers have developed alternative concepts of cisgenesis and intragenesis which involve transformation of plants with genetic material derived from the species itself or from closely related species capable of sexual hybridization, respectively. Recombinase technology aimed at site-specific integration of transgene can help to overcome limitations of traditional genetic engineering methods based on random integration of multiple copy of transgene into plant genome leading to gene silencing and unpredictable expression pattern. Besides, recently developed technology of genome editing using engineered nucleases, permit the modification or mutation of genes of interest without involving foreign DNA, and as a result, plants developed with this technology might be considered as non-transgenic genetically altered plants. This would open the doors for the development and commercialization of transgenic plants with superior phenotypes even in countries where GM crops are poorly accepted. This review is an attempt to summarize various past achievements of GM technology in crop improvement, recent progress and new advances in the field to develop improved varieties aimed for better consumer acceptance. PMID- 27381852 TI - Biology of ICEBs1, an integrative and conjugative element in Bacillus subtilis. AB - Horizontal gene transfer plays a profound role in bacterial evolution by propelling the rapid transfer of genes and gene cassettes. Integrative and conjugative elements (ICEs) are one important mechanism driving horizontal gene transfer. ICEs, also known as conjugative transposons, reside on the host chromosome but can excise to form a conjugative DNA circle that is capable of transfer to other cells. Analysis of the large number of completed bacterial genome sequences has revealed many previously unrecognized ICEs, including ICEBs1, found in the Gram-positive model bacterium Bacillus subtilis. The discovery of ICEBs1 in an organism with such an impressive array of molecular tools for genetics and molecular biology was fortuitous. Significant insights into ICE biology have resulted since its discovery <15years ago. In this review, we describe aspects of ICEBs1 biology, such as excision, conjugative transfer, and reintegration, likely to be conserved across many ICEs. We will also highlight some of the more unexpected aspects of ICEBs1 biology, such as its ability to undergo plasmid-like replication after excision and its ability to mobilize plasmids lacking dedicated mobilization functions. A molecular understanding of ICEBs1 has led to additional insights into signals and mechanisms that promote horizontal gene transfer and shape bacterial evolution. PMID- 27381853 TI - Smell of migraine: Osmophobia as a clinical diagnostic marker? PMID- 27381854 TI - Longitudinal changes in cerebral blood flow velocities in different clinical courses of migraine. AB - Objective To assess longitudinal changes in cerebral blood flow velocities (DeltaCBFVs) according to the clinical course of migraine. Methods We retrospectively included migraine patients with two or more attacks per month at baseline who were followed up within 2 years with transcranial Doppler in a tertiary headache clinic. DeltaCBFVs were analyzed in relation to clinical courses, defined as remission (0-1 headache days/month), persistence (2 14/month), or progression (>=15/month) in episodic migraine (EM), and conversion to EM (<15/month) and persistence (>=15/month) in chronic migraine (CM). Results A total of 166 patients (90 EM and 76 CM) were included. In EM, the remission group ( n = 30) showed a decrease in CBFV in the middle cerebral artery (MCA) and the basilar artery (BA). The progression group ( n = 10) showed increasing CBFVs in the bilateral MCAs. Patients with the persistence course ( n = 50) showed generally unchanged CBFVs. In CM, DeltaCBFVs decreased in the BA and increased in the posterior cerebral artery (PCA) after conversion to EM ( n = 61), whereas they remained unchanged in the persistence group ( n = 15). In all patients, % change in headache days was positively correlated with the %DeltaCBFVs of the bilateral MCAs and the BA. Conclusions CBFV changes are associated with the different clinical courses of migraine. The association is more prominent in EM than CM. PMID- 27381855 TI - Benefit of low-dose tamoxifen in a large observational cohort of high risk ER positive breast DCIS. AB - Low-dose tamoxifen has comparable antiproliferative effect to the standard dose of 20 mg/day in biomarker trials, but its clinical efficacy remains unclear. We assessed the effect of low-dose tamoxifen on ipsilateral recurrence in ductal carcinoma in situ (DCIS) patients treated in a referral Institution between 1996 and 2008. Following conserving surgery, women received radiotherapy and/or low dose tamoxifen upon clinical judgment and patient preferences. Cox regression analyses were used with and without confounding factors. Among 1,091 women with DCIS and median age 53 years (IQR: 46-62), 544 (49.9%) received radiotherapy. Of the 833 women with oestrogen receptor (ER) positive DCIS, 467 (56.1%) received low-dose tamoxifen. After a median of 7.7 years, 235 ipsilateral recurrences and 62 contralateral breast tumors were observed. Low-dose tamoxifen significantly decreased any breast event (HR = 0.70, 95% CI: 0.54-0.91) and ipsilateral DCIS recurrence (HR = 0.66, 95% CI: 0.49-0.88), but not ipsilateral invasive recurrence or contralateral tumors. Radiotherapy showed a large significant reduction for any breast event (HR = 0.55, 95% CI: 0.42-0.72). Tamoxifen was more effective on all breast events in women aged >50 years than in women aged <=50 (HR = 0.51, 95% CI: 0.33-0.77 versus HR = 0.84, 95% CI: 0.60-1.18, p-interaction = 0.03). Age <=50 years, positive margins, high Ki67, high grade and low BMI were independent predictors of ipsilateral recurrence. No increase of endometrial cancers and fewer deaths (p = 0.015) were observed on tamoxifen. Low-dose tamoxifen seems to be safe and effective in reducing ipsilateral recurrence in ER positive DCIS in women aged >50 years. A randomized trial is underway to confirm these findings. PMID- 27381856 TI - Thioredoxin interacting protein (TXNIP) regulates tubular autophagy and mitophagy in diabetic nephropathy through the mTOR signaling pathway. AB - Hyperglycemia upregulates thioredoxin interacting protein (TXNIP) expression, which in turn induces ROS production, inflammatory and fibrotic responses in the diabetic kidney. Dysregulation of autophagy contributes to the development of diabetic nephropathy. However, the interaction of TXNIP with autophagy/mitophagy in diabetic nephropathy is unknown. In this study, streptozotocin-induced diabetic rats were given TXNIP DNAzyme or scrambled DNAzyme for 12 weeks respectively. Fibrotic markers, mitochondrial function and mitochondrial reactive oxygen species (mtROS) were assessed in kidneys. Tubular autophagy and mitophagy were determined in kidneys from both human and rats with diabetic nephropathy. TXNIP and autophagic signaling molecules were examined. TXNIP DNAzyme dramatically attenuated extracellular matrix deposition in the diabetic kidneys compared to the control DNAzyme. Accumulation of autophagosomes and reduced autophagic clearance were shown in tubular cells of human diabetic compared to non-diabetic kidneys, which was reversed by TXNIP DNAzyme. High glucose induced mitochondrial dysfunction and mtROS production, and inhibited mitophagy in proximal tubular cells, which was reversed by TXNIP siRNA. TXNIP inhibition suppressed diabetes-induced BNIP3 expression and activation of the mTOR signaling pathway. Collectively, hyperglycemia-induced TXNIP contributes to the dysregulation of tubular autophagy and mitophagy in diabetic nephropathy through activation of the mTOR signaling pathway. PMID- 27381857 TI - Sleep deprivation increases formation of false memory. AB - Retrieving false information can have serious consequences. Sleep is important for memory, but voluntary sleep curtailment is becoming more rampant. Here, the misinformation paradigm was used to investigate false memory formation after 1 night of total sleep deprivation in healthy young adults (N = 58, mean age +/- SD = 22.10 +/- 1.60 years; 29 males), and 7 nights of partial sleep deprivation (5 h sleep opportunity) in these young adults and healthy adolescents (N = 54, mean age +/- SD = 16.67 +/- 1.03 years; 25 males). In both age groups, sleep-deprived individuals were more likely than well-rested persons to incorporate misleading post-event information into their responses during memory retrieval (P < 0.050). These findings reiterate the importance of adequate sleep in optimal cognitive functioning, reveal the vulnerability of adolescents' memory during sleep curtailment, and suggest the need to assess eyewitnesses' sleep history after encountering misleading information. PMID- 27381858 TI - Association between comorbidities and absence of chest pain in acute coronary syndrome with in-hospital outcome. AB - BACKGROUND: To evaluate the impact of comorbidities on the management and outcomes of acute coronary syndrome (ACS) patients without chest pain/discomfort (i.e. ACS without typical presentation). METHODS: Of the 11,458 ACS patients, enrolled by the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC; ClinicalTrials.gov: NCT01218776), 8.7% did not have typical presentation at the initial evaluation, and 40.2% had comorbidities. The odds of atypical presentation increased proportionally with the number of comorbidities (odds ratio [OR]: 1, no-comorbid; OR: 1.64, 1 comorbidity; OR: 2.52, 2 comorbidities; OR: 4.57, >=3 comorbidities). RESULTS: Stratifying the study population by the presence/absence of comorbidities and typical presentation, we found a decreasing trend for use of medications and percutaneous intervention (OR: 1, typical presentation and no-comorbidities; OR: 0.70, typical presentation and comorbidities; OR: 0.23, atypical presentation and no-comorbidities; OR: 0.18, atypical presentation and comorbidities). On the opposite, compared with patients with typical presentation and no-comorbidities (OR: 1, referent), there was an increasing trend (p<0.001) in the risk of death (OR: 2.00, OR: 2.52 and OR: 4.83) in the above subgroups. However, after adjusting for comorbidities, medications and invasive procedures, atypical presentation was not a predictor of in-hospital death. Independent predictors of poor outcome were history of stroke (OR: 2.04), chronic kidney disease (OR: 1.57), diabetes mellitus (OR: 1.49) and underuse of invasive procedures. CONCLUSIONS: In the ISACS-TC, atypical ACS presentation was often associated with comorbidities. Atypical presentation and comorbidities influenced underuse of in-hospital treatments. The latter and comorbidities are related with poor in-hospital outcome, but not atypical presentation, per se. PMID- 27381859 TI - Factors associated with use of percutaneous coronary intervention among elderly patients presenting with ST segment elevation acute myocardial infarction (STEMI): Results from the ISACS-TC registry. AB - BACKGROUND: A substantial proportion of elderly with ST segment elevation myocardial infarction (STEMI) do not undergo percutaneous coronary intervention (PCI). We sought to investigate factors associated with the decision not to perform coronary angiography at admission in these patients. METHODS: We evaluated 1315 STEMI patients aged >=75years old enrolled in the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS TC) registry between October 2010 and February 2015. They were compared with 6667 patients aged <75years old enrolled in the registry in the same time frame. RESULTS: Elderly patients were less likely to undertake invasive coronary evaluation compared with younger patients (62.1% vs. 78.9; p<0.001%). In the older group there were a lower proportion of patients presenting <12h after symptom onset (66.5% vs.76.9%, p<0.001), and a higher prevalence of comorbidities. Few elderly were treated with current recommended evidence based treatments (aspirin, clopidogrel, heparins, beta-blocker, statins, and ACE-inhibitors). Logistic analysis adjusted for age and sex showed that older age was associated with underuse of coronary angiography (OR 0.46, 95% CI: 0.41-0.53, p<0.001). Clinical factors that were associated with underuse of angiography in patients over 75 were: female sex (OR: 0.77), presence of comorbidities (OR: 0.91), anemia (OR: 0.44) and late hospital admission (OR: 0.89). CONCLUSIONS: In the ISACS-TC, more than one third of the elderly with STEMI did not undergo coronary angiography at admission. Sex, comorbidities, and late hospital admission were independent factors associated with the underuse of PCI in these patients. PMID- 27381860 TI - Acute coronary syndromes in low- and middle-income countries: Moving forward. AB - Cardiovascular disease remains the leading cause of death worldwide, particularly in low- and middle-income countries (LMICs), with substantial mortality from acute coronary syndromes. These deaths, when compared against high-income countries, occur at younger ages, and, beyond the lives lost, often result in economic privation for families deprived of a breadwinner and indebted by the oftentimes catastrophic cost of inpatient medical care. This burden will likely grow in scale in the years ahead as more countries pass through the epidemiologic transition. Billions around the world are beginning to experience the comforts that even modestly increased incomes can provide, including diets high in fats and sugars, more sedentary lifestyles, and tobacco and alcohol use and abuse. Health care systems in many of these countries are ill-equipped to prevent the harms caused by these lifestyles, as well as treat the acute coronary syndromes that result from them-including insufficient access to appropriate facilities and medications, difficulties with transport, and low awareness of the symptoms and need for emergent evaluation. PMID- 27381861 TI - Optimizing prevention and guideline-concordant care in Montenegro. AB - BACKGROUND: Guidelines recommend use of evidence-based medications in patients discharged after an acute coronary syndrome (ACS). Yet the current rates of adherence in many eastern European countries are unknown. OBJECTIVE: To determine whether 6month outpatient follow-up after ACS is associated with recommended rates of medication adherence in Montenegro. METHODS: A prospective analysis was conducted in 585 ACS patients confirmed to be alive after ACS at 6month follow up. The study was undertaken between 2012 and 2015, from 9 International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC) hospitals in the Montenegro. The primary outcome was guideline-concordant care, defined as 100% compliance with 5 medications: aspirin, clopidogrel, beta-blockers, and statins in ACS patients, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers [ACEI/ARB] for the subset of patients with left ventricular systolic dysfunction, as assessed by an ejection fraction less than 40% at discharge. In addition to the composite end point, the achievement of each single treatment measure was analyzed. Multivariate predictors of long-term medication adherence were also identified. RESULTS: Guideline-concordant care (GCC) at discharge increased from 2012 to 2015 (adjusted OR for increase 1.51; CI 0.88 2.52). GCC over 6months was adhered in 73% of patients. In patients who did not achieve GCC, adherence was persistently high with 92.3% for aspirin, 91.3% for statins and 72% for ACE-inhibitors or angiotensin-receptor blockers (ARBs). Adherence was lower for clopidogrel (57.7%) and beta-blockers (64.4%). After adjusting for demographic and clinical differences, in-hospital referral to PCI and ST segment elevation myocardial infarction (STEMI) were associated with greater medication adherence at 6month follow-up. CONCLUSIONS: In Montenegro, long-term adherence to evidence-based medication after ACS is high. Adherence to guideline-recommended therapies increased over time with participation to the ISACS-TC. The lower achievement of GCC in patients treated medically and in those with non-ST-segment elevation ACS needs particular attention. PMID- 27381862 TI - Primary percutaneous coronary intervention network in Bosnia and Herzegovina: Where are we now and how to improve PCI network. AB - Reperfusion is the most effective therapy for patients with ST segment elevation myocardial infarction (STEMI). Time from symptom onset to reperfusion is the most important factor influencing short and long-term mortality. There are several modes of reperfusion therapy. Fibrinolysis (either in pre-hospital or in-hospital setting), and primary percutaneous coronary intervention (p-PCI) or a combination of both are the most relevant treatment options. Primary p-PCI is the preferred option in centers with experienced teams and a high volume of reperfusion procedures. Cardiovascular mortality rate in Bosnia and Herzegovina (B&H) is among the highest in Europe, 545/100,000, and the rate of acute myocardial infarction is approximately 7000 per year. Despite recent improvement in reperfusion therapy in the last 5years, mortality of STEMI still patients remains high. The goal of this perspective article is to describe the current situation of p-PCI network in B&H. Establishing networks of reperfusion at regional and national level, implies a broad spectrum and close collaboration between all the actors involved in reperfusion therapy, namely hospitals, cardiology units emergency medical services, and primary care physicians. PMID- 27381864 TI - LncRNA FER1L4 suppresses cancer cell proliferation and cycle by regulating PTEN expression in endometrial carcinoma. AB - BACKGROUND: Dysregulated long non-coding RNAs (lncRNAs) might exert key roles in pathways associated with endometrial carcinoma (EC) development. This study aims to investigate the new role of lncRNA FER1L4 in EC pathogenesis due to its correlation with phosphatase and tensin homolog (PTEN), one important indicator of EC progression. METHODS: Real time PCR was performed to detect the expression of FER1L4 in thirty paired EC samples and two EC cell lines. Plasmid containing FER1L4 was transfected into HEC-50 cells with a relative lower level of FER1L4 expression, followed which PTEN expression and Akt phosphorylation were measured by western blotting. Cell proliferation was analyzed through MTT and colony formation assays, while cell cycle and apoptosis were determined by flow cytometry. RESULTS: FER1L4 showed significantly downregulation in EC tissues compared to control, which was positively correlated with decreased PTEN expression. Moreover, FER1L4 could promote PTEN expression and inhibit Akt phosphorylation. Additionally, a significant decrease of cell proliferation was observed in FER1L4 overexpressing cells, along with cell cycle arrest at G0/G1 phase and increased proportion of apoptotic cells. CONCLUSION: FER1L4 not only showed downregulation in EC tissues and cells, but also regulated PTEN expression and Akt signaling, which might contribute to its inhibition on cell proliferation. This study might provide a new potential therapeutic target for EC treatment. PMID- 27381865 TI - Crystal structure of Cry6Aa: A novel nematicidal ClyA-type alpha-pore-forming toxin from Bacillus thuringiensis. AB - Crystal (Cry) proteins from Bacillus thuringiensis (Bt) are globally used in agriculture as proteinaceous insecticides. Numerous crystal structures have been determined, and most exhibit conserved three-dimensional architectures. Recently, we have identified a novel nematicidal mechanism by which Cry6Aa triggers cell death through a necrosis-signaling pathway via an interaction with the host protease ASP-1. However, we found little sequence conservation of Cry6Aa in our functional study. Here, we report the 1.90 angstrom (A) resolution structure of the proteolytic form of Cry6Aa (1-396), determined by X-ray crystallography. The structure of Cry6Aa is highly similar to those of the pathogenic toxin family of ClyA-type alpha-pore-forming toxins (alpha-PFTs), which are characterized by a bipartite structure comprising a head domain and a tail domain, thus suggesting that Cry6Aa exhibits a previously undescribed nematicidal mode of action. This structure also provides a framework for the functional study of other nematicidal toxins. PMID- 27381866 TI - All-trans retinoic acid ameliorates glycemic control in diabetic mice via modulating pancreatic islet production of vascular endothelial growth factor-A. AB - Patients with type 1 diabetes mellitus are associated with impairment in vitamin A metabolism. This study evaluated whether treatment with retinoic acid, the biologically active metabolite of vitamin A, can ameliorate diabetes. All-trans retinoic acid (atRA) was used to treat streptozotocin (STZ)-induced diabetic mice which revealed atRA administration ameliorated blood glucose levels of diabetic mice. This hyperglycemic amelioration was accompanied by an increase in the amount of beta cells co-expressed Pdx1 and insulin and by restoration of the vascular laminin expression. The atRA-induced production of vascular endothelial growth factor-A from the pancreatic islets was possibly the key factor that mediated the restoration of islet vascularity and recovery of beta-cell mass. Furthermore, the combination of islet transplantation and atRA administration significantly rescued hyperglycemia in diabetic mice. These findings suggest that vitamin A derivatives can potentially be used as a supplementary treatment to improve diabetes management and glycemic control. PMID- 27381867 TI - Dimethoxycurcumin, a metabolically stable analogue of curcumin enhances the radiosensitivity of cancer cells: Possible involvement of ROS and thioredoxin reductase. AB - Dimethoxycurcumin (DIMC), a structural analogue of curcumin, has been shown to have more stability, bioavailability, and effectiveness than its parent molecule curcumin. In this paper the radiosensitizing effect of DIMC has been investigated in A549 lung cancer cells. As compared to its parent molecule curcumin, DIMC showed a very potent radiosensitizing effect as seen by clonogenic survival assay. DIMC in combination with radiation significantly increased the apoptosis and mitotic death in A549 cells. This combinatorial treatment also lead to effective elimination of cancer stem cells. Further, there was a significant increase in cellular ROS, decrease in GSH to GSSG ratio and also significant slowdown in DNA repair when DIMC was combined with radiation. In silico docking studies and in vitro studies showed inhibition of thioredoxin reductase enzyme by DIMC. Overexpression of thioredoxin lead to the abrogation of radiosensitizing effect of DIMC underscoring the role of thioredoxin reductase in radiosensitization. Our results clearly demonstrate that DIMC can synergistically enhance the cancer cell killing when combined with radiation by targeting thioredoxin system. PMID- 27381868 TI - Association between comprehensive health literacy and frailty level in community dwelling older adults: A cross-sectional study in Japan. AB - AIM: The present study explored the association between comprehensive health literacy and frailty level in community-dwelling older adults in Japan. METHODS: This was a cross-sectional study. We enrolled 517 community-dwelling older adults (mean age 73.2 +/- 6.3 years; 410 women). We divided the cohort into two groups, non-frail and any-frail, based on Fried Frailty Index scores. We assessed comprehensive health literacy using a 14-item health literacy scale, and classified the participants as having high or low health literacy. We carried out multivariate logistic regression analysis in which the dependent variable was the presence of non-frailty and the independent variable was the presence of high health literacy. The analysis was adjusted for age, sex, body mass index, educational history and cognitive function. RESULTS: There were 132 (25.5%) and 385 (74.5%) participants in the non-frail and any-frail groups, respectively. The analysis showed that high health literacy was independently associated with the non-frail group (odds ratio 1.64, 95% confidence interval 1.03-2.61). CONCLUSIONS: The results showed that high health literacy was associated with non frailty. This result implies that comprehensive health literacy might play a salient role in maintaining good health status in community-dwelling older adults in Japan. Geriatr Gerontol Int 2017; 17: 804-809. PMID- 27381870 TI - Determination of biogenic amines in licorice (Glycyrrhiza glabra) by ion-pair extraction and liquid chromatography-tandem mass spectrometry. AB - BACKGROUND: Ion-pair extraction combined with liquid chromatography-tandem mass spectrometry method has been proposed for the determination of biogenic amines in licorice samples. RESULTS: Limit of detection and limit of quantitation for the biogenic amines were 1.4-2.7 and 4.7-9.1 ng mL-1 , respectively. Relative standard deviations based on five replicate extraction of 100 ng mL-1 of each biogenic amine were <4.7% for intra-day and 7.4% for inter-day precision. The method described in this study has been shown to be in accordance with satisfactory accuracy and good reproducibility for the quantitative determination of biogenic amines in licorice samples. Nine biogenic amines (putrescine, cadaverine, histamine, spermine, spermidine, tyramine, tryptamine, agmatine and phenylethylamine) were detected in licorice samples and total biogenic amine concentrations were determined at 369 ng mL-1 in fresh and 3532 ng mL-1 in non fresh licorice samples. Putrescine was found at the highest concentrations to be up to 704 ng mL-1 in all the analyzed samples, followed by tyramine (675 ng mL-1 ) and tryptamine (282 ng mL-1 ). Putrescine, tyramine and spermine concentrations were dramatically increased, whereas agmatine concentration was significantly decreased, in non-fresh licorice samples compared to fresh ones. CONCLUSION: The consumption of freshly prepared licorice is recommended because of the relatively low concentration of total biogenic amines. (c) 2016 Society of Chemical Industry. PMID- 27381869 TI - Neural activity in the medial parietal area V6A while grasping with or without visual feedback. AB - Recent works have reported that grasping movements are controlled not only by the dorsolateral visual stream, as generally thought, but also by the dorsomedial visual stream, and in particular by the medial posterior parietal area V6A. To date, the grasping activity of V6A neurons has been studied only in darkness. Here we studied the effect of visual feedback on grasp-related discharges of V6A neurons while the monkey was preparing and executing the grasping of a handle. We found that V6A grasping activity could be excited or inhibited by visual information. The neural population was divided into Visual, Motor, and Visuomotor cells. The majority of Visual and Visuomotor neurons did not respond to passive observation of the handle, suggesting that vision of action, rather than object vision, is the most effective factor. The present findings highlight the role of the dorsomedial visual stream in integrating visual and motor signals to monitor and correct grasping. PMID- 27381871 TI - In vitro enantioselective human liver microsomal metabolism and prediction of in vivo pharmacokinetic parameters of tetrabenazine by DLLME-CE. AB - A new capillary electrophoresis method for the enantioselective analysis of cis- and trans- dihydrotetrabenazine (diHTBZ) after in vitro metabolism by human liver microsomes (HLMs) was developed. The chiral electrophoretic separations were performed by using tris-phosphate buffer (pH 2.5) containing 1% (w/v) carboxymethyl-beta-CD as background electrolyte with an applied voltage of +15kV and capillary temperature kept at 15 degrees C. Dispersive liquid-liquid microextraction was employed to extract the analytes from HLMs. Dichloromethane was used as extraction solvent (75MUL) and acetone as disperser solvent (150MUL). The method was validated according to official guidelines and showed to be linear over the concentration range of 0.29-19.57MUmolL(-1) (r=0.9955) for each metabolite enantiomer. Within- and between-day precision and accuracy evaluated by relative standard deviation and relative error were lower than 15% for all enantiomers. The stability assay showed that the analytes kept stable under handling, storage and in metabolism conditions. After method validation, an enantioselective in vitro metabolism and in vivo pharmacokinetic prediction was carried out. This study showed a stereoselective metabolism and the observed kinetic profile indicated a substrate inhibition behavior. DiHTBZ enantiomers were catalyzed mainly by CYP2C19 and the predicted clearance suggests that liver metabolism is the main route for TBZ elimination which supports the literature data. PMID- 27381872 TI - Association of maternal serum cadmium level during pregnancy with risk of preterm birth in a Chinese population. AB - Cadmium (Cd) was a developmental toxicant that induces fetal malformation and growth restriction in mice. However, epidemiological studies about the association of maternal serum Cd level with risk of preterm birth were limited. This study was to investigate whether maternal serum Cd level during pregnancy is associated with risk of preterm birth in a Chinese population. Total 3254 eligible mother-and-singleton-offspring pairs were recruited. Maternal serum Cd level was measured by GFAAS. Based on tertiles, maternal serum Cd concentration was classified as low (LCd, <0.65 MUg/L), medium (MCd, 0.65-0.94 MUg/L) and high (HCd, >=0.95 MUg/L). Odds ratio (OR) for preterm birth was estimated using multiple logistic regression models. Results showed the rate of preterm birth among LCd, M-Cd and HCd was 3.5%, 3.8%, and 9.4%, respectively. Subjects with HCd had a significantly higher risk for preterm birth (OR: 2.86; 95%CI: 1.95, 4.19; P < 0.001) than did those with LCd. Adjusted OR for preterm birth was 3.02 (95%CI: 2.02, 4.50; P < 0.001) among subjects with HCd compared to subjects with LCd. Taken together, the above results suggest that maternal serum Cd level during pregnancy is positively associated with risk of preterm birth. PMID- 27381873 TI - Regional differences in plant levels and investigations on the phytotoxicity of lithium. AB - The growing use of lithium (Li) in industrial and energetic applications and the inability to completely recycle the alkali metal will most likely increase anthropogenic emissions and environmental concentrations in the future. Although non-essential to plants, Li(+) is an important ultra-trace element in the animal and human diet and is also used in the treatment of e.g. mental disorders. Most of the lithium is consumed with the drinking water and vegetables, but concentrations in foodstuffs vary with the geochemistry of the element. In order to identify potential risks and to avoid an overmedication due to consumption of Li rich or Li contaminated foods it is advisable to identify background levels and to derive recommended Daily Allowances (RDAs) for the element. Although Germany does not possess large amounts of primary or secondary resources of lithium, geochemical investigations (mineral and ground waters and soils) in this country confirm a wide variation of environmental concentrations with generally higher levels in the southwest. Despite the large number of soil and water data, only very few data exist on lithium concentrations in plants and its phytotoxicity. Within the scope of present study common grassland plant species were sampled in regions of SW-Germany with reportedly high geogenic levels of Li. The data are discussed with regard to literature surveys and existing reference values. Since lithium has phytotoxic effects a greenhouse experiment was performed with different Li salts (LiCl and Li2CO3) and plant species (maize, bean and buckwheat) to derive dose-response relationships for the endpoint shoot growth. While corn growth was not reduced significantly by soil concentrations of 118 ppm, EC50 values in buckwheat were 47 and 16 ppm for lithium derived from LiCl and Li2CO3, respectively. PMID- 27381874 TI - The roles of protein and lipid in the accumulation and distribution of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in plants grown in biosolids-amended soils. AB - The roles of protein and lipid in the accumulation and distribution of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in seven species of plants from biosolids-amended soils were investigated. The PFOS and PFOA root concentration factors (Croot/Csoil) ranged from 1.37 to 4.68 and 1.69 to 10.3 (ng/groot)/(ng/gsoil), respectively, while the translocation factors (Cshoot/Croot) ranged from 0.055 to 0.16 and 0.093 to 1.8 (ng/gshoot)/(ng/groot), respectively. The PFOS and PFOA accumulations in roots correlated positively with root protein contents (P < 0.05), while negatively with root lipid contents (P < 0.05). These suggested the promotion effects of protein and inhibition effects of lipid on root uptake. The translocation factors correlated positively with the ratios between protein contents in shoots to those in roots (P < 0.05), showing the importance of protein on PFOS and PFOA translocation. This study is the first to reveal the different roles of protein and lipid in the accumulation and distribution of PFOS and PFOA in plants. PMID- 27381875 TI - Microplastics in Taihu Lake, China. AB - In comparison with marine environments, the occurrence of microplastics in freshwater environments is less understood. In the present study, we investigated microplastic pollution levels during 2015 in Taihu Lake, the third largest Chinese lake located in one of the most developed areas of China. The abundance of microplastics reached 0.01 * 10(6)-6.8 * 10(6) items/km(2) in plankton net samples, 3.4-25.8 items/L in surface water, 11.0-234.6 items/kg dw in sediments and 0.2-12.5 items/g ww in Asian clams (Corbicula fluminea). The average abundance of microplastics was the highest in plankton net samples from the southeast area of the lake and in the sediments from the northwest area of the lake. The northwest area of the lake was the most heavily contaminated area of the lake, as indicated by chlorophyll-alpha and total phosphorus. The microplastics were dominated by fiber, 100-1000 MUm in size and cellophane in composition. To our best knowledge, the microplastic levels measured in plankton net samples collected from Taihu Lake were the highest found in freshwater lakes worldwide. The ratio of the microplastics in clams to each sediment sample ranged from 38 to 3810 and was negatively correlated to the microplastic level in sediments. In brief, our results strongly suggest that high levels of microplastics occurred not only in water but also in organisms in Taihu Lake. PMID- 27381876 TI - The Effect of a Freely Available Flipped Classroom Course on Health Care Worker Patient Safety Culture: A Prospective Controlled Study. AB - BACKGROUND: Patient safety culture is an integral aspect of good standard of care. A good patient safety culture is believed to be a prerequisite for safe medical care. However, there is little evidence on whether general education can enhance patient safety culture. OBJECTIVE: Our aim was to assess the impact of a standardized patient safety course on health care worker patient safety culture. METHODS: Health care workers from Intensive Care Units (ICU) at two hospitals (A and B) in Hong Kong were recruited to compare the changes in safety culture before and after a patient safety course. The BASIC Patient Safety course was administered only to staff from Hospital A ICU. Safety culture was assessed in both units at two time points, one before and one after the course, by using the Hospital Survey on Patient Safety Culture questionnaire. Responses were coded according to the Survey User's Guide, and positive response percentages for each patient safety domain were compared to the 2012 Agency for Healthcare Research and Quality ICU sample of 36,120 respondents. RESULTS: We distributed 127 questionnaires across the two hospitals with an overall response rate of 74.8% (95 respondents). After the safety course, ICU A significantly improved on teamwork within hospital units (P=.008) and hospital management support for patient safety (P<.001), but decreased in the frequency of reporting mistakes compared to the initial survey (P=.006). Overall, ICU A staff showed significantly greater enhancement in positive responses in five domains than staff from ICU B. Pooled data indicated that patient safety culture was poorer in the two ICUs than the average ICU in the Agency for Healthcare Research and Quality database, both overall and in every individual domain except hospital management support for patient safety and hospital handoffs and transitions. CONCLUSIONS: Our study demonstrates that a structured, reproducible short course on patient safety may be associated with an enhancement in several domains in ICU patient safety culture. PMID- 27381878 TI - Migration of a foreign object to the parapharyngeal space: an unusual factitious disorder. PMID- 27381877 TI - Can we use the questionnaire SNOT-22 as a predictor for the indication of surgical treatment in chronic rhinosinusitis? AB - INTRODUCTION: Chronic rhinosinusitis is a prevalent disease that has a negative impact on the lives of sufferers. SNOT-22 is considered the most appropriate questionnaire for assessing the quality of life of these patients and a very effective method of evaluating therapeutic interventions; however it is not used as a tool for decision-making. OBJECTIVE: To test the hypothesis that the SNOT-22 score can predict the outcome of surgical treatment. METHODS: A retrospective, longitudinal and analytical study. We evaluated the medical records of patients with chronic rhinosinusitis that completed the SNOT-22 at the time of diagnosis. All the patients were consecutively receiving care at an otolaryngology service in Salvador, Bahia from August 2011 to June 2012. The outcomes of the surgical treatment of these patients were obtained from their medical records. The initial score was compared to a group of patients who were not referred for surgery. All the patients completed and signed a consent form. RESULTS: Of the 88 patients with chronic rhinosinusitis, 26 had evolved to surgery over the last 3 years. The groups were homogeneous regarding gender and respiratory and medication allergies. The patients of the surgical group were 44.8+13.8 years old and the patients of the clinical group were 38.2+12.5 years old (p=0.517). The average SNOT-22 score of the case group was 49+19 and the average score of the control group was 49+27 (p=0.927). CONCLUSION: The SNOT-22 was unable to predict the outcome of surgical patients with chronic rhinosinusitis. PMID- 27381879 TI - Prostatic carcinoma metastatic to frontal and cavernous sinuses: a case report. PMID- 27381880 TI - Development of particulate drug formulation against C. parvum: Formulation, characterization and in vivo efficacy. AB - This research aims towards developing an alternative therapy against Cryptosporidium parvum using bioadhesive paromomycin and diloxanide furoate loaded microspheres. Microspheres were prepared using chitosan and poly(vinyl alcohol) and two types of cyclodextrins (beta-CD and DM-beta-CD) for the potential use of treating cryptosporidiosis. This pathogen is associated with gastrointestinal illness in humans and animals. Microparticle formulations were characterized in terms of size, surface charge, drug release and morphology. In vivo bioadhesion properties of CHI/PVA microspheres were also evaluated in mice. Finally, the in vivo efficacy of CHI/PVA microspheres against C. parvum was tested in neonatal mouse model. In this work, microspheres prepared by spray drying showed spherical shape, diameters between 6.67+/-0.11 and 18.78+/-0.07MUm and positively surface charged. The bioadhesion studies demonstrated that MS remained attached at +16h (post-infection) to the intestinal cells as detected by fluorescence. This finding was crucial taking use of the fact that the parasite multiplication occurs between 16 and 20h post-infection. The efficacy of treatment was determined by calculating the number of oocysts recovered from the intestinal tract of mice after 7days of post-infection. Mice receiving orally administered microspheres with and without drug exhibited significantly lower parasite loads compared with the control mice. Ultrastructural observations by TEM bring to light the uptake of smallest particles by enterocytes associated with conspicuous changes in enterocytic cells. Completely recovery of cell morphology was detected after 24h of first inoculation with MS. CHI/PVA microspheres appear to be a safe and simple system to be used in an anticryptosporidial treatment. The distinctive features of neonatal mice requires further work to determine the suppressive effect of this particulate delivery system on C. parvum attachment in other animal models. PMID- 27381881 TI - The effect of multivitamin-multimineral supplementation on the health status of inbred Wistar and spontaneously hypertensive rat strains. AB - The nutraceutical industry has proliferated in recent years, with the most popular form of supplementation being the multivitamin-multimineral (MVMM) supplement. In the animal health sector, supplement use has also expanded. The objective of this study was to determine the effects of MVMM supplementation, beneficial or otherwise, on the general health status of the spontaneously hypertensive rat (SHR) strain, an animal model used in hypertension research. A commercially prepared MVMM supplement was given tri-weekly via oral dosing for 8 weeks to two groups of seven adult female SHR and Wistar rats. Their corresponding control groups were dosed with deionised water only. Systolic and diastolic blood pressure, fasting blood glucose, growth rate and food and water intake were measured weekly. At the end of 8 weeks, the animals were euthanased and a full blood profile, urine sodium to potassium ratio, blood urea nitrogen levels and total plasma cholesterol was measured for all groups. The results indicated that growth rate was higher for the SHR supplemented group. Supplementation also decreased diastolic blood pressure in both Wistar and SHR groups and increased red blood cell count and decreased total cholesterol in the SHR group. No adverse effects on the general health status of the animals were observed. MVMM supplementation may therefore be useful in aiding growth and delaying the onset of hypertension and its effects. It may also assist in the longevity of the breeding stock of SHR rats. PMID- 27381882 TI - Multiple morphological clocks and total-evidence tip-dating in mammals. AB - Morphological integration predicts that correlated characters will coevolve; thus, each distinct suite of correlated characters might be expected to evolve according to a separate clock or 'pacemaker'. Characters in a large morphological dataset for mammals were found to be evolving according to seven separate clocks, each distinct from the molecular clock. Total-evidence tip-dating using these multiple clocks inflated divergence time estimates, but potentially improved topological inference. In particular, single-clock analyses placed several meridiungulates and condylarths in a heterodox position as stem placentals, but multi-clock analyses retrieved a more plausible and orthodox position within crown placentals. Several shortcomings (including uneven character sampling) currently impact upon the accuracy of total-evidence dating, but this study suggests that when sufficiently large and appropriately constructed phenotypic datasets become more commonplace, multi-clock approaches are feasible and can affect both divergence dates and phylogenetic relationships. PMID- 27381883 TI - The rise of ocean giants: maximum body size in Cenozoic marine mammals as an indicator for productivity in the Pacific and Atlantic Oceans. AB - Large consumers have ecological influence disproportionate to their abundance, although this influence in food webs depends directly on productivity. Evolutionary patterns at geologic timescales inform expectations about the relationship between consumers and productivity, but it is very difficult to track productivity through time with direct, quantitative measures. Based on previous work that used the maximum body size of Cenozoic marine invertebrate assemblages as a proxy for benthic productivity, we investigated how the maximum body size of Cenozoic marine mammals, in two feeding guilds, evolved over comparable temporal and geographical scales. First, maximal size in marine herbivores remains mostly stable and occupied by two different groups (desmostylians and sirenians) over separate timeframes in the North Pacific Ocean, while sirenians exclusively dominated this ecological mode in the North Atlantic. Second, mysticete whales, which are the largest Cenozoic consumers in the filter-feeding guild, remained in the same size range until a Mio-Pliocene onset of cetacean gigantism. Both vertebrate guilds achieved very large size only recently, suggesting that different trophic mechanisms promoting gigantism in the oceans have operated in the Cenozoic than in previous eras. PMID- 27381884 TI - Goats display audience-dependent human-directed gazing behaviour in a problem solving task. AB - Domestication is an important factor driving changes in animal cognition and behaviour. In particular, the capacity of dogs to communicate in a referential and intentional way with humans is considered a key outcome of how domestication as a companion animal shaped the canid brain. However, the lack of comparison with other domestic animals makes general conclusions about how domestication has affected these important cognitive features difficult. We investigated human directed behaviour in an 'unsolvable problem' task in a domestic, but non companion species: goats. During the test, goats experienced a forward-facing or an away-facing person. They gazed towards the forward-facing person earlier and for longer and showed more gaze alternations and a lower latency until the first gaze alternation when the person was forward-facing. Our results provide strong evidence for audience-dependent human-directed visual orienting behaviour in a species that was domesticated primarily for production, and show similarities with the referential and intentional communicative behaviour exhibited by domestic companion animals such as dogs and horses. This indicates that domestication has a much broader impact on heterospecific communication than previously believed. PMID- 27381885 TI - Personality composition alters the transmission of cuticular bacteria in social groups. AB - The initial stages of a disease outbreak can determine the magnitude of the ensuing epidemic. Though rarely tested in unison, two factors with important consequences for the transmission dynamics of infectious agents are the collective traits of the susceptible population and the individual traits of the index case (i.e. 'patient zero'). Here, we test whether the personality composition of a social group can explain horizontal transmission dynamics of cuticular bacteria using the social spider Stegodyphus dumicola We exposed focal spiders of known behavioural phenotypes with a GFP-transformed cuticular bacterium (Pantoea sp.) and placed them in groups of 10 susceptible individuals (i.e. those with no experience with this bacterium). We measured bacterial transmission to groups composed of either all shy spiders, 10% bold spiders or 40% bold spiders. We found that colonies with 40% bold spiders experienced over twice the incidence of transmission compared to colonies with just 10% bold individuals after only 24 h of interaction. Colonies of all shy spiders experienced an intermediate degree of transmission. Interestingly, we did not detect an effect of the traits of the index case on transmission. These data suggest that the phenotypic composition of the susceptible population can have a greater influence on the degree of early transmission events than the traits of the index case. PMID- 27381886 TI - Indirect reciprocity can overcome free-rider problems on costly moral assessment. AB - Indirect reciprocity is one of the major mechanisms of the evolution of cooperation. Because constant monitoring and accurate evaluation in moral assessments tend to be costly, indirect reciprocity can be exploited by cost evaders. A recent study crucially showed that a cooperative state achieved by indirect reciprocators is easily destabilized by cost evaders in the case with no supportive mechanism. Here, we present a simple and widely applicable solution that considers pre-assessment of cost evaders. In the pre-assessment, those who fail to pay for costly assessment systems are assigned a nasty image that leads to them being rejected by discriminators. We demonstrate that considering the pre assessment can crucially stabilize reciprocal cooperation for a broad range of indirect reciprocity models. In particular for the most leading social norms, we analyse the conditions under which a prosocial state becomes locally stable. PMID- 27381888 TI - Tribute to Michael Dunn for his dedication and contribution to proteomics and stem cell focus. PMID- 27381887 TI - Staphylococcus aureus Exploits Epidermal Barrier Defects in Atopic Dermatitis to Trigger Cytokine Expression. AB - Patients with atopic dermatitis (AD) have an abnormal skin barrier and are frequently colonized by S. aureus. In this study we investigated if S. aureus penetrates the epidermal barrier of subjects with AD and sought to understand the mechanism and functional significance of this entry. S. aureus was observed to be more abundant in the dermis of lesional skin from AD patients. Bacterial entry past the epidermis was observed in cultured human skin equivalents and in mice but was found to be increased in the skin of cathelicidin knockout and ovalbumin sensitized filaggrin mutant mice. S. aureus penetration through the epidermis was dependent on bacterial viability and protease activity, because killed bacteria and a protease-null mutant strain of S. aureus were unable to penetrate. Entry of S. aureus directly correlated with increased expression of IL-4, IL-13, IL-22, thymic stromal lymphopoietin, and other cytokines associated with AD and with decreased expression of cathelicidin. These data illustrate how abnormalities of the epidermal barrier in AD can alter the balance of S. aureus entry into the dermis and provide an explanation for how such dermal dysbiosis results in increased inflammatory cytokines and exacerbation of disease. PMID- 27381889 TI - Impact of Repeated Tail Clip and Saphenous Vein Phlebotomy on Rats Used in Toxicology Studies. AB - Sampling blood for toxicokinetic (TK) evaluation in rodents is typically performed using a satellite group of animals to avoid depleting the blood volume and inducing an additional stressor in the main study animals. This practice does not allow for direct comparison of individual animal toxicity to exposure. These studies evaluated serial collection of twelve, 40-ul blood samples from each rat from either a tail clip or a saphenous vein bleed and its impact on toxicologic parameters over 4- and 14-day periods. The results show the feasibility of successfully collecting TK samples from main study animals, using either of the two techniques. Both procedures were amenable to execution by a single technician using dried blood spot sampling. Any changes observed in the primary markers of erythroid mass between the nonbled control rats and repeat sampled rats were minimal and the range of values often overlapped. This technique would improve the quality of data generated from toxicology studies by allowing a direct comparison of systemic exposure to toxicity while at the same time reducing the number of rats by obviating the need for satellite groups. PMID- 27381890 TI - Monosubstituted Benzene Derivatives from Fruits of Ficus hirta and Their Antifungal Activity against Phytopathogen Penicillium italicum. AB - Ficus hirta, a widely consumed food by Hakka people, has been reported to show potent antifungal activity against phytopathogen Penicillium italicum. However, there is no report of chemical constituents responsible for the antifungal activity. In the current study, nine monosubstituted benzene derivatives, including three new derivatives (1-3), were isolated from the fruits of F. hirta. The structures of these isolates were elucidated on the basis of the analysis of spectroscopic data (mass spectrometry and nuclear magnetic resonance). All of the isolates were evaluated for antifungal activities against P. italicum. At an equivalent concentration, compound 1 exhibited stronger antifungal activity than that of the ethanol extract of F. hirta fruits. PMID- 27381891 TI - In Situ Single-Nanoparticle Spectroscopy Study of Bimetallic Nanostructure Formation. AB - Bimetallic nanostructures (NSs), with utility in catalysis, are typically prepared using galvanic exchange (GE), but the final catalyst morphology is dictated by the dynamics of the process. In situ single nanoparticle (NP) optical scattering spectroscopy, coupled with ex situ electron microscopy, is used to capture the dynamic structural evolution of a bimetallic NS formed in a GE reaction between Ag and [PtCl6 ](2-) . We identify an early stage involving anisotropic oxidation of Ag to AgCl concomitant with reductive deposition of small Pt clusters on the NS surface. At later stages of GE, unreacted Ag inclusions phase segregate from the overcoated AgCl as a result of lattice strain between Ag and AgCl. The nature of the structural evolution elucidates why multi domain Ag/AgCl/Pt NSs result from the GE process. The complex structural dynamics, determined from single-NP trajectories, would be masked in ensemble studies due to heterogeneity in the response of different NPs. PMID- 27381892 TI - Comparison of capacitive and radio frequency resonator sensors for monitoring parallelized droplet microfluidic production. AB - Scaled-up production of microfluidic droplets, through the parallelization of hundreds of droplet generators, has received a lot of attention to bring novel multiphase microfluidics research to industrial applications. However, apart from droplet generation, other significant challenges relevant to this goal have never been discussed. Examples include monitoring systems, high-throughput processing of droplets and quality control procedures among others. In this paper, we present and compare capacitive and radio frequency (RF) resonator sensors as two candidates that can measure the dielectric properties of emulsions in microfluidic channels. By placing several of these sensors in a parallelization device, the stability of the droplet generation at different locations can be compared, and potential malfunctions can be detected. This strategy enables for the first time the monitoring of scaled-up microfluidic droplet production. Both sensors were prototyped and characterized using emulsions with droplets of 100 150 MUm in diameter, which were generated in parallelization devices at water-in oil volume fractions (phi) between 11.1% and 33.3%.Using these sensors, we were able to measure accurately increments as small as 2.4% in the water volume fraction of the emulsions. Although both methods rely on the dielectric properties of the emulsions, the main advantage of the RF resonator sensors is the fact that they can be designed to resonate at multiple frequencies of the broadband transmission line. Consequently with careful design, two or more sensors can be parallelized and read out by a single signal. Finally, a comparison between these sensors based on their sensitivity, readout cost and simplicity, and design flexibility is also discussed. PMID- 27381893 TI - Replacing cystoscopy by urine markers in the follow-up of patients with low-risk non-muscle-invasive bladder cancer?-An International Bladder Cancer Network project. AB - RATIONALE: Numerous molecular urine markers for the diagnosis of bladder cancer have been developed and evaluated mostly in case-control settings through the past decades. However, despite all efforts none of them has been included into clinical decision-making and guideline recommendations until today. The aim of this retrospective longitudinal analysis was to investigate if a molecular marker might be able to replace cystoscopy as a primary examination in diagnosis and follow-up of patients with pTa grade 1-2 bladder cancer. MATERIALS AND METHODS: Totally 36 patients (32 men) with pTa grade 1-2 bladder cancer underwent 232 follow-up examinations including urine analysis, cytology, immunocytology (uCyt+), and urethrocystoscopy (UC). Mean age at study entry was 63 years. Patients were observed through a median follow-up interval of 3.8 years. RESULTS: In summary, 47 Transurethral Resection of Bladder Tumors (TURB) procedures were indicated based upon a positive UC (44) or as re-TURB (3) and 33 tumors (plus 1 case of pTa G0) were histopathologically confirmed. Although uCyt+was positive in 12/13 primary tumors (92.3%), sensitivity dropped to 13/20 (65%) in tumor recurrence presumably because of their smaller size. Urine cytology had a sensitivity and a specificity of 30.3% and 94.9%, respectively, but did not improve the sensitivity of uCyt+alone. If UC was based upon a positive uCyt+test, 8/33 tumors (24.2%) would have been overlooked or diagnosed late. In contrast, 173 UCs (74%) would have been saved and 5 presumably unnecessary TURB procedures would not have been indicated. CONCLUSIONS: This longitudinal study suggests a potential of molecular urine tests in replacing cystoscopy in the follow-up of patients with pTa G1-2 bladder cancer. The use of additional markers might further improve sensitivity of urine testing. A prospective randomized study has been initiated to prospectively investigate the performance of a marker panel against UC. PMID- 27381894 TI - Epithelial-mesenchymal transition (EMT) phenotype at invasion front of squamous cell carcinoma of the penis influences oncological outcomes. AB - OBJECTIVE: Our aims were to evaluate epithelial-mesenchymal transition (EMT) as a useful prognostic marker in penile carcinoma (PC), and establish an objective criterion to define EMT in PC specimens. MATERIALS AND METHODS: A total of 149 consecutive cases surgically treated for PC were retrospectively selected. E cadherin (E-CAD) and vimentin immunohistochemical expressions were evaluated. A combined analysis was performed using both markers to determine EMT status. To establish a normal control to E-CAD expression, we included 14 cases from circumcisions from patients without any neoplastic disease and 77 cases of tumor free margins. The analyses of tumor samples were evaluated in 2 different areas of the tumor. The first one was in the tumor core. The second analyses were performed on the deepest infiltrative edge of the tumor, nominated invasion front. Cases were classified into EMT absent group, partial EMT group and complete EMT group. Overall survival (OS) and cancer-specific survival (CSS) were analyzed. Kaplan-Meier curves and the log-rank test were used. Cox proportional hazards model was used to determine which variables influenced survival. RESULTS: Tumor specimens presented a significant loss of expression of E-CAD when compared with normal epithelium. Vimentin expression in more than 10% of tumor cells was observed in 50 cases. EMT status was associated with histologic grade, pattern of invasion, lymph node metastasis, and perineural and vascular invasion. Further, 10-year OS and CSS rates in patients with presence and absence of complete EMT status were 38.0% and 55.6%; and 48.0% and 91.9%, respectively. EMT status significantly affected CSS and OS rates even after patients were grouped based on lymph node involvement status. The presence of complete EMT status was associated with both CSS and OS rates. Patients in the complete EMT group had a higher risk of death from cancer (hazard ratio = 7.6, P<0.001) and overall death (hazard ratio = 3.0, P<0.001). CONCLUSION: Our study represents an evidence of the prognostic effect of EMT in PC. We encourage the study of EMT markers in other centers to validate our findings and confirm its importance in such tumors. PMID- 27381895 TI - Acute and late urinary toxicity following radiation in men with an intact prostate gland or after a radical prostatectomy: A secondary analysis of RTOG 94 08 and 96-01. AB - INTRODUCTION: To estimate the contribution of the prostate gland and prostatic urethral inflammation to urinary symptoms after radiation therapy for prostate cancer, we performed a secondary analysis of urinary toxicity after primary radiation to an intact prostate vs. postprostatectomy radiation to the prostatic fossa in protocols RTOG 94-08 and 96-01, respectively. MATERIALS AND METHODS: Patients randomized to the radiation-alone arms (without hormone therapy) of the 2 trials were evaluated, including 104 men receiving primary prostate radiation to 68.4Gy on RTOG 94-08 and 371 men receiving 64.8Gy to the prostatic fossa on RTOG 96-01. Acute and late urinary toxicity were scored prospectively by RTOG scales. Chi-square test/logistic regression and cumulative incidence approach/Fine-Gray regression model were used for analyses of acute and late toxicity, respectively. RESULTS: Grade>=2 acute urinary toxicity was significantly higher after primary prostatic radiation compared with postprostatectomy radiation (30.8% vs. 14.0%; P<0.001), but acute grade>=3 toxicity did not differ (3.8% vs. 2.7%; P = 0.54). After adjusting for age, primary radiation resulted in significantly higher grade>=2 acute urinary toxicity (odds ratio = 3.72; 95% CI: 1.65-8.37; P = 0.02). With median follow-up of 7.1 years, late urinary toxicity was not significantly different with primary vs. postprostatectomy radiation (5-year grade>=2: 16.7% vs. 18.3%; P = 0.65; grade>=3: 6.0% vs. 3.3%; P = 0.24). CONCLUSIONS: Primary radiation to an intact prostate resulted in higher grade>=2 acute urinary toxicity than radiation to the prostatic fossa, with no difference in late urinary toxicity. Thus, a proportion of acute urinary toxicity in men with an intact prostate may be attributable to inflammation of the prostatic gland or urethra. PMID- 27381896 TI - Limited improvement of incorporating primary circulating prostate cells with the CAPRA score to predict biochemical failure-free outcome of radical prostatectomy for prostate cancer. AB - OBJECTIVE: To establish a prediction model for early biochemical failure based on the Cancer of the Prostate Risk Assessment (CAPRA) score, the presence or absence of primary circulating prostate cells (CPC) and the number of primary CPC (nCPC)/8ml blood sample is detected before surgery. PATIENTS AND METHODS: A prospective single-center study of men who underwent radical prostatectomy as monotherapy for prostate cancer. Clinical-pathological findings were used to calculate the CAPRA score. Before surgery blood was taken for CPC detection, mononuclear cells were obtained using differential gel centrifugation, and CPCs identified using immunocytochemistry. A CPC was defined as a cell expressing prostate-specific antigen and P504S, and the presence or absence of CPCs and the number of cells detected/8ml blood sample was registered. Patients were followed up for up to 5 years; biochemical failure was defined as a prostate-specific antigen>0.2ng/ml. The validity of the CAPRA score was calibrated using partial validation, and the fractional polynomial Cox proportional hazard regression was used to build 3 models, which underwent a decision analysis curve to determine the predictive value of the 3 models with respect to biochemical failure. RESULTS: A total of 267 men participated, mean age 65.80 years, and after 5 years of follow-up the biochemical-free survival was 67.42%. The model using CAPRA score showed a hazards ratio (HR) of 5.76 between low and high-risk groups, that of CPC with a HR of 26.84 between positive and negative groups, and the combined model showed a HR of 4.16 for CAPRA score and 19.93 for CPC. Using the continuous variable nCPC, there was no improvement in the predictive value of the model compared with the model using a positive-negative result of CPC detection. The combined CAPRA-nCPC model showed an improvement of the predictive performance for biochemical failure using the Harrell's C concordance test and a net benefit on DCA in comparison with either model used separately. The use of primary CPC as a predictive factor based on their presence or absence did not predict aggressive disease or biochemical failure. CONCLUSION: Although the use of a combined CAPRA nCPC model improves the prediction of biochemical failure in patients undergoing radical prostatectomy for prostate cancer, this is minimal. The use of the presence or absence of primary CPCs alone did not predict aggressive disease or biochemical failure. PMID- 27381897 TI - Assessment of Layer Thickness and Interface Quality in CoP Electrodeposited Multilayers. AB - The magnetic properties of CoP electrodeposited alloys can be easily controlled by layering the alloys and modulating the P content of the different layers by using pulse plating in the electrodeposition process. However, because of its amorphous nature, the study of the interface quality, which is a limitation for the optimization of the soft magnetic properties of these alloys, becomes a complex task. In this work, we use Rutherford backscattering spectroscopy (RBS) to determine that electrodeposited Co0.74P0.26/Co0.83P0.17 amorphous multilayers with layers down to 20 nm-thick are composed by well-defined layers with interfacial roughness below 3 nm. We have also determined, using magnetostriction measurements, that 4 nm is the lower limitation for the layer thickness. Below this thickness, the layers are mixed and the magnetic behavior of the multilayered films is similar to that shown by single layers, thus going from in plane to out-of-plane magnetic anisotropy. Therefore, these results establish the range in which the magnetic properties of these alloys can be controlled by layering. PMID- 27381898 TI - Phenylbutyrate exerts adverse effects on liver regeneration and amino acid concentrations in partially hepatectomized rats. AB - Phenylbutyrate is recommended in urea cycle disorders and liver injury to enhance nitrogen disposal by the urine. However, hypothetically there may be adverse responses to the use of phenylbutyrate in the treatment of liver disease because of its role as a histone deacetylase inhibitor and its stimulatory effect on branched-chain alpha-keto acid dehydrogenase, the rate-limiting enzyme in the catabolism of branched-chain amino acids (BCAA; valine, leucine and isoleucine). We report the effects of phenylbutyrate on liver regeneration and amino acid levels in plasma of partially hepatectomized (PH) rats. Phenylbutyrate or saline was administered at 12-h intervals to PH or laparotomized rats. Phenylbutyrate delayed the onset of liver regeneration compared to the saline-treated controls, as indicated by lower hepatic DNA specific activities 18 and 24( ) h post-PH, decreased hepatic fractional protein synthesis rates 24 h post-PH and lowered the increases in liver weights and hepatic protein and DNA contents 48 h after PH. Hepatic DNA fragmentation (a hallmark of apoptosis) was higher in the phenylbutyrate-treated animals than in controls. Phenylbutyrate decreased the glutamine and BCAA concentrations and the ratio of the BCAA to aromatic amino acids (phenylalanine and tyrosine) in the blood plasma in both hepatectomized and laparotomized animals. In conclusion, the delayed onset of liver regeneration and the decrease in BCAA/AAA ratio in blood suggest that phenylbutyrate administration may be disastrous in subjects with acute hepatic injury and BCAA supplementation is needed when phenylbutyrate is used therapeutically. PMID- 27381899 TI - Development, Validation, and Verification of a Self-Assessment Tool to Estimate Agnibala (Digestive Strength). AB - According to Ayurveda, the traditional system of healthcare of Indian origin, Agni is the factor responsible for digestion and metabolism. Four functional states (Agnibala) of Agni have been recognized: regular, irregular, intense, and weak. The objective of the present study was to develop and validate a self assessment tool to estimate Agnibala The developed tool was evaluated for its reliability and validity by administering it to 300 healthy volunteers of either gender belonging to 18 to 40-year age group. Besides confirming the statistical validity and reliability, the practical utility of the newly developed tool was also evaluated by recording serum lipid parameters of all the volunteers. The results show that the lipid parameters vary significantly according to the status of Agni The tool, therefore, may be used to screen normal population to look for possible susceptibility to certain health conditions. PMID- 27381901 TI - Appeasing the Carotid Body After Chronic Intermittent Hypoxia. PMID- 27381900 TI - A Genetic Response Score for Hydrochlorothiazide Use: Insights From Genomics and Metabolomics Integration. AB - Hydrochlorothiazide is among the most commonly prescribed antihypertensives; yet, <50% of hydrochlorothiazide-treated patients achieve blood pressure (BP) control. Herein, we integrated metabolomic and genomic profiles of hydrochlorothiazide treated patients to identify novel genetic markers associated with hydrochlorothiazide BP response. The primary analysis included 228 white hypertensives treated with hydrochlorothiazide from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study. Genome-wide analysis was conducted using Illumina Omni 1 mol/L-Quad Chip, and untargeted metabolomics was performed on baseline fasting plasma samples using a gas chromatography-time-of flight mass spectrometry platform. We found 13 metabolites significantly associated with hydrochlorothiazide systolic BP (SBP) and diastolic BP (DBP) responses (false discovery rate, <0.05). In addition, integrating genomic and metabolomic data revealed 3 polymorphisms (rs2727563 PRKAG2, rs12604940 DCC, and rs13262930 EPHX2) along with arachidonic acid, converging in the netrin signaling pathway (P=1*10(-5)), as potential markers, significantly influencing hydrochlorothiazide BP response. We successfully replicated the 3 genetic signals in 212 white hypertensives treated with hydrochlorothiazide and created a response score by summing their BP-lowering alleles. We found patients carrying 1 response allele had a significantly lower response than carriers of 6 alleles (?SBP/?DBP: -1.5/1.2 versus -16.3/-10.4 mm Hg, respectively, SBP score, P=1*10( 8) and DBP score, P=3*10(-9)). This score explained 11.3% and 11.9% of the variability in hydrochlorothiazide SBP and DBP responses, respectively, and was further validated in another independent study of 196 whites treated with hydrochlorothiazide (DBP score, P=0.03; SBP score, P=0.07). This study suggests that PRKAG2, DCC, and EPHX2 might be important determinants of hydrochlorothiazide BP response. PMID- 27381902 TI - Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats. AB - Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) chemosensory responses to hypoxia and produces autonomic dysfunction, cardiac arrhythmias, and hypertension. We tested whether autonomic alterations, arrhythmogenesis, and the progression of hypertension induced by CIH depend on the enhanced CB chemosensory drive, by ablation of the CB chemoreceptors. Male Sprague-Dawley rats were exposed to control (Sham) conditions for 7 days and then to CIH (5% O2, 12/h 8 h/d) for a total of 28 days. At 21 days of CIH exposure, rats underwent bilateral CB ablation and then exposed to CIH for 7 additional days. Arterial blood pressure and ventilatory chemoreflex response to hypoxia were measured in conscious rats. In addition, cardiac autonomic imbalance, cardiac baroreflex gain, and arrhythmia score were assessed during the length of the experiments. In separate experimental series, we measured extracellular matrix remodeling content in cardiac atrial tissue and systemic oxidative stress. CIH induced hypertension, enhanced ventilatory response to hypoxia, induced autonomic imbalance toward sympathetic preponderance, reduced baroreflex gain, and increased arrhythmias and atrial fibrosis. CB ablation normalized blood pressure, reduced ventilatory response to hypoxia, and restored cardiac autonomic and baroreflex function. In addition, CB ablation reduced the number of arrhythmias, but not extracellular matrix remodeling or systemic oxidative stress, suggesting that reductions in arrhythmia incidence during CIH were related to normalization of cardiac autonomic balance. Present results show that autonomic alterations induced by CIH are critically dependent on the CB and support a main role for the CB in the CIH-induced hypertension. PMID- 27381904 TI - Pomalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 1 and 2 trial. AB - The objectives of a phase 1/2 trial of pomalidomide with dexamethasone for the treatment of light chain (AL) amyloidosis were to determine the safety, tolerability, maximum tolerated dose (MTD), recommended phase 2 dose, and hematologic and clinical response. A 3+3 dose-escalation phase (15 patients) was followed by an expansion cohort (12 patients) enrolled at the MTD. Pomalidomide was administered at 2 and 3 mg on days 1 to 28 (cohorts 1 and 2) and 4 mg on days 1 to 21 (cohort 3) every 28 days, with weekly dexamethasone at a dose of 20 mg. Twenty-seven patients with previously treated AL were enrolled, 15 during dose escalation (6 at 2 mg, 3 at 3 mg, and 6 at 4 mg) and 12 during dose expansion (all at 4 mg). One patient experienced dose-limiting toxicity at 4 mg; the MTD was determined as 4 mg. The most common grade >=3 drug-related adverse events included myelosuppression and fatigue. Overall, hematologic response (HR) was 50% in 24 evaluable patients. The median time to best HR was 3 cycles, and median duration of HR was 15 months. Median overall survival has not yet been reached, with a median follow-up of 17.1 months and median event-free survival of 17.8 months. This trial was registered at www.clinicaltrials.gov as #NCT01570387. PMID- 27381903 TI - Advances in the understanding of trauma-induced coagulopathy. AB - Ten percent of deaths worldwide are due to trauma, and it is the third most common cause of death in the United States. Despite a profound upregulation in procoagulant mechanisms, one-quarter of trauma patients present with laboratory based evidence of trauma-induced coagulopathy (TIC), which is associated with poorer outcomes including increased mortality. The most common causes of death after trauma are hemorrhage and traumatic brain injury (TBI). The management of TIC has significant implications in both because many hemorrhagic deaths could be preventable, and TIC is associated with progression of intracranial injury after TBI. This review covers the most recent evidence and advances in our understanding of TIC, including the role of platelet dysfunction, endothelial activation, and fibrinolysis. Trauma induces a plethora of biochemical and physiologic changes, and despite numerous studies reporting differences in coagulation parameters between trauma patients and uninjured controls, it is unclear whether some of these differences may be "normal" after trauma. Comparisons between trauma patients with differing outcomes and use of animal studies have shed some light on this issue, but much of the data continue to be correlative with causative links lacking. In particular, there are little data linking the laboratory-based abnormalities with true clinically evident coagulopathic bleeding. For these reasons, TIC continues to be a significant diagnostic and therapeutic challenge. PMID- 27381905 TI - High-affinity, noninhibitory pathogenic C1 domain antibodies are present in patients with hemophilia A and inhibitors. AB - Inhibitor formation in hemophilia A is the most feared treatment-related complication of factor VIII (fVIII) therapy. Most inhibitor patients with hemophilia A develop antibodies against the fVIII A2 and C2 domains. Recent evidence demonstrates that the C1 domain contributes to the inhibitor response. Inhibitory anti-C1 monoclonal antibodies (mAbs) have been identified that bind to putative phospholipid and von Willebrand factor (VWF) binding epitopes and block endocytosis of fVIII by antigen presenting cells. We now demonstrate by competitive enzyme-linked immunosorbent assay and hydrogen-deuterium exchange mass spectrometry that 7 of 9 anti-human C1 mAbs tested recognize an epitope distinct from the C1 phospholipid binding site. These mAbs, designated group A, display high binding affinities for fVIII, weakly inhibit fVIII procoagulant activity, poorly inhibit fVIII binding to phospholipid, and exhibit heterogeneity with respect to blocking fVIII binding to VWF. Another mAb, designated group B, inhibits fVIII procoagulant activity, fVIII binding to VWF and phospholipid, fVIIIa incorporation into the intrinsic Xase complex, thrombin generation in plasma, and fVIII uptake by dendritic cells. Group A and B epitopes are distinct from the epitope recognized by the canonical, human-derived inhibitory anti-C1 mAb, KM33, whose epitope overlaps both groups A and B. Antibodies recognizing group A and B epitopes are present in inhibitor plasmas from patients with hemophilia A. Additionally, group A and B mAbs increase fVIII clearance and are pathogenic in a hemophilia A mouse tail snip bleeding model. Group A anti-C1 mAbs represent the first identification of pathogenic, weakly inhibitory antibodies that increase fVIII clearance. PMID- 27381906 TI - Long noncoding RNAs in B-cell development and activation. AB - Long noncoding RNAs (lncRNAs) are potentially important regulators of cell differentiation and development, but little is known about their roles in B lymphocytes. Using RNA-seq and de novo transcript assembly, we identified 4516 lncRNAs expressed in 11 stages of B-cell development and activation. Most of these lncRNAs have not been previously detected, even in the closely related T cell lineage. Comparison with lncRNAs previously described in human B cells identified 185 mouse lncRNAs that have human orthologs. Using chromatin immunoprecipitation-seq, we classified 20% of the lncRNAs as either enhancer associated (eRNA) or promoter-associated RNAs. We identified 126 eRNAs whose expression closely correlated with the nearest coding gene, thereby indicating the likely location of numerous enhancers active in the B-cell lineage. Furthermore, using this catalog of newly discovered lncRNAs, we show that PAX5, a transcription factor required to specify the B-cell lineage, bound to and regulated the expression of 109 lncRNAs in pro-B and mature B cells and 184 lncRNAs in acute lymphoblastic leukemia. PMID- 27381908 TI - Continuing Medical Education activity in Echocardiography July 2016. PMID- 27381909 TI - Assessment of Myocardial Function in Children before and after Autologous Peripheral Blood Stem Cell Transplantation: The Effect of Autologous Peripheral Blood Stem Cell Transplantation on Biventricular Systolic Function. PMID- 27381910 TI - A Simplified Model of Moisture Transport in Hydrophilic Porous Media With Applications to Pharmaceutical Tablets. AB - This work establishes a predictive model that explicitly recognizes microstructural parameters in the description of the overall mass uptake and local gradients of moisture into tablets. Model equations were formulated based on local tablet geometry to describe the transient uptake of moisture. An analytical solution to a simplified set of model equations was solved to predict the overall mass uptake and moisture gradients with the tablets. The analytical solution takes into account individual diffusion mechanisms in different scales of porosity and diffusion into the solid phase. The time constant of mass uptake was found to be a function of several key material properties, such as tablet relative density, pore tortuosity, and equilibrium moisture content of the material. The predictions of the model are in excellent agreement with experimental results for microcrystalline cellulose tablets without the need for parameter fitting. The model presented provides a new method to analyze the transient uptake of moisture into hydrophilic materials with the knowledge of only a few fundamental material and microstructural parameters. In addition, the model allows for quick and insightful predictions of moisture diffusion for a variety of practical applications including pharmaceutical tablets, porous polymer systems, or cementitious materials. PMID- 27381911 TI - Reconstitution and Minimization of a Micrococcin Biosynthetic Pathway in Bacillus subtilis. AB - Thiopeptides represent one of several families of highly modified peptide antibiotics that hold great promise for natural product engineering. These macrocyclic peptides are produced by a combination of ribosomal synthesis and extensive posttranslational modification by dedicated processing enzymes. We previously identified a compact, plasmid-borne gene cluster for the biosynthesis of micrococcin P1 (MP1), an archetypal thiopeptide antibiotic. In an effort to genetically dissect this pathway, we have reconstituted it in Bacillus subtilis Successful MP1 production required promoter engineering and the reassembly of essential biosynthetic genes in a modular plasmid. The resulting system allows for rapid pathway manipulation, including protein tagging and gene deletion. We find that 8 processing proteins are sufficient for the production of MP1 and that the tailoring enzyme TclS catalyzes a C-terminal reduction step that distinguishes MP1 from its sister compound micrococcin P2. IMPORTANCE: The emergence of antibiotic resistance is one of the most urgent human health concerns of our day. A crucial component in an integrated strategy for countering antibiotic resistance is the ability to engineer pathways for the biosynthesis of natural and derivatized antimicrobial compounds. In this study, the model organism B. subtilis was employed to reconstitute and genetically modularize a 9 gene system for the biosynthesis of micrococcin, the founding member of a growing family of thiopeptide antibiotics. PMID- 27381912 TI - Analyzing Neisseria gonorrhoeae Pilin Antigenic Variation Using 454 Sequencing Technology. AB - Many pathogens use homologous recombination to vary surface antigens in order to avoid immune surveillance. Neisseria gonorrhoeae, the bacterium responsible for the sexually transmitted infection gonorrhea, achieves this in part by changing the sequence of the major subunit of the type IV pilus in a process termed pilin antigenic variation (Av). The N. gonorrhoeae chromosome contains one expression locus (pilE) and many promoterless, partial-coding silent copies (pilS) that act as reservoirs for variant pilin information. Pilin Av occurs by high-frequency gene conversion reactions, which transfer pilS sequences into the pilE locus. We have developed a 454 sequencing-based assay to analyze the frequency and characteristics of pilin Av that allows a more robust analysis of pilin Av than previous assays. We used this assay to analyze mutations and conditions previously shown to affect pilin Av, confirming many but not all of the previously reported phenotypes. We show that mutations or conditions that cause growth defects can result in Av phenotypes when analyzed by phase variation-based assays. Adapting the 454 sequencing to analyze pilin Av demonstrates the utility of this technology to analyze any diversity generation system that uses recombination to develop biological diversity. IMPORTANCE: Measuring and analyzing complex recombination-based systems constitute a major barrier to understanding the mechanisms used to generate diversity. We have analyzed the contributions of many gonococcal mutations or conditions to the process of pilin antigenic variation. PMID- 27381913 TI - Primary and Secondary Sequence Structure Requirements for Recognition and Discrimination of Target RNAs by Pseudomonas aeruginosa RsmA and RsmF. AB - CsrA family RNA-binding proteins are widely distributed in bacteria and regulate gene expression at the posttranscriptional level. Pseudomonas aeruginosa has a canonical member of the CsrA family (RsmA) and a novel, structurally distinct variant (RsmF). To better understand RsmF binding properties, we performed parallel systematic evolution of ligands by exponential enrichment (SELEX) experiments for RsmA and RsmF. The initial target library consisted of 62 nucleotide (nt) RNA transcripts with central cores randomized at 15 sequential positions. Most targets selected by RsmA and RsmF were the expected size and shared a common consensus sequence (CANGGAYG) that was positioned in a hexaloop region of the stem-loop structure. RsmA and RsmF also selected for longer targets (>=96 nt) that were likely generated by rare PCR errors. Most of the long targets contained two consensus-binding sites. Representative short (single consensus site) and long (two consensus sites) targets were tested for RsmA and RsmF binding. Whereas RsmA bound the short targets with high affinity, RsmF was unable to bind the same targets. RsmA and RsmF both bound the long targets. Mutation of either consensus GGA site in the long targets reduced or eliminated RsmF binding, suggesting a requirement for two tandem binding sites. Conversely, RsmA bound long targets containing only a single GGA site with unaltered affinity. The RsmF requirement for two binding sites was confirmed with tssA1, an in vivo regulatory target of RsmA and RsmF. Our findings suggest that RsmF binding requires two GGA containing sites, while RsmA binding requirements are less stringent. IMPORTANCE: The CsrA family of RNA-binding proteins is widely conserved in bacteria and plays important roles in the posttranscriptional regulation of protein synthesis. P. aeruginosa has two CsrA proteins, RsmA and RsmF. Although RsmA and RsmF share a few RNA targets, RsmF is unable to bind to other targets recognized by RsmA. The goal of the present study was to better understand the basis for differential binding by RsmF. Our data indicate that RsmF binding requires target RNAs with two consensus-binding sites, while RsmA recognizes targets with just a single binding site. This information should prove useful to future efforts to define the RsmF regulon and its contribution to P. aeruginosa physiology and virulence. PMID- 27381914 TI - A Combined Computational and Genetic Approach Uncovers Network Interactions of the Cyanobacterial Circadian Clock. AB - Two-component systems (TCS) that employ histidine kinases (HK) and response regulators (RR) are critical mediators of cellular signaling in bacteria. In the model cyanobacterium Synechococcus elongatus PCC 7942, TCSs control global rhythms of transcription that reflect an integration of time information from the circadian clock with a variety of cellular and environmental inputs. The HK CikA and the SasA/RpaA TCS transduce time information from the circadian oscillator to modulate downstream cellular processes. Despite immense progress in understanding of the circadian clock itself, many of the connections between the clock and other cellular signaling systems have remained enigmatic. To narrow the search for additional TCS components that connect to the clock, we utilized direct coupling analysis (DCA), a statistical analysis of covariant residues among related amino acid sequences, to infer coevolution of new and known clock TCS components. DCA revealed a high degree of interaction specificity between SasA and CikA with RpaA, as expected, but also with the phosphate-responsive response regulator SphR. Coevolutionary analysis also predicted strong specificity between RpaA and a previously undescribed kinase, HK0480 (herein CikB). A knockout of the gene for CikB (cikB) in a sasA cikA null background eliminated the RpaA phosphorylation and RpaA-controlled transcription that is otherwise present in that background and suppressed cell elongation, supporting the notion that CikB is an interactor with RpaA and the clock network. This study demonstrates the power of DCA to identify subnetworks and key interactions in signaling pathways and of combinatorial mutagenesis to explore the phenotypic consequences. Such a combined strategy is broadly applicable to other prokaryotic systems. IMPORTANCE: Signaling networks are complex and extensive, comprising multiple integrated pathways that respond to cellular and environmental cues. A TCS interaction model, based on DCA, independently confirmed known interactions and revealed a core set of subnetworks within the larger HK-RR set. We validated high-scoring candidate proteins via combinatorial genetics, demonstrating that DCA can be utilized to reduce the search space of complex protein networks and to infer undiscovered specific interactions for signaling proteins in vivo Significantly, new interactions that link circadian response to cell division and fitness in a light/dark cycle were uncovered. The combined analysis also uncovered a more basic core clock, illustrating the synergy and applicability of a combined computational and genetic approach for investigating prokaryotic signaling networks. PMID- 27381915 TI - Experimental Analysis of Functional Variation within Protein Families: Receiver Domain Autodephosphorylation Kinetics. AB - Plants and microorganisms use two-component signal transduction systems (TCSs) to mediate responses to environmental stimuli. TCSs mediate responses through phosphotransfer from a conserved histidine on a sensor kinase to a conserved aspartate on the receiver domain of a response regulator. Typically, signal termination occurs through dephosphorylation of the receiver domain, which can catalyze its own dephosphorylation. Despite strong structural conservation between receiver domains, reported autodephosphorylation rate constants (kdephos) span a millionfold range. Variable receiver domain active-site residues D + 2 and T + 2 (two amino acids C terminal to conserved phosphorylation site and Thr/Ser, respectively) influence kdephos values, but the extent and mechanism of influence are unclear. We used sequence analysis of a large database of naturally occurring receiver domains to design mutant receiver domains for experimental analysis of autodephosphorylation kinetics. When combined with previous analyses, kdephos values were obtained for CheY variants that contained D + 2/T + 2 pairs found in 54% of receiver domain sequences. Tested pairs of amino acids at D + 2/T + 2 generally had similar effects on kdephos in CheY, PhoBN, or Spo0F. Acid or amide residues at D + 2/T + 2 enhanced kdephos CheY variants altered at D + 2/T + 2 exhibited rate constants for autophosphorylation with phosphoramidates and autodephosphorylation that were inversely correlated, suggesting that D + 2/T + 2 residues interact with aspects of the ground or transition states that differ between the two reactions. kdephos of CheY variants altered at D + 2/T + 2 correlated significantly with kdephos of wild-type receiver domains containing the same D + 2/T + 2 pair. Additionally, particular D + 2/T + 2 pairs were enriched in different response regulator subfamilies, suggesting functional significance. IMPORTANCE: One protein family, defined by a conserved domain, can include hundreds of thousands of known members. Characterizing conserved residues within a conserved domain can identify functions shared by all family members. However, a general strategy to assess features that differ between members of a family is lacking. Fully exploring the impact of just two variable positions within a conserved domain could require assessment of 400 (i.e., 20 * 20) variants. Instead, we created and analyzed a nonredundant database of receiver domain sequences. Five percent of D + 2/T + 2 pairs were sufficient to represent 50% of receiver domain sequences. Using protein sequence analysis to prioritize mutant choice made it experimentally feasible to extensively probe the influence of positions D + 2 and T + 2 on receiver domain autodephosphorylation kinetics. PMID- 27381916 TI - Choline Catabolism in Burkholderia thailandensis Is Regulated by Multiple Glutamine Amidotransferase 1-Containing AraC Family Transcriptional Regulators. AB - Burkholderia thailandensis is a soil-dwelling bacterium that shares many metabolic pathways with the ecologically similar, but evolutionarily distant, Pseudomonas aeruginosa Among the diverse nutrients it can utilize is choline, metabolizable to the osmoprotectant glycine betaine and subsequently catabolized as a source of carbon and nitrogen, similar to P. aeruginosa Orthologs of genes in the choline catabolic pathway in these two bacteria showed distinct differences in gene arrangement as well as an additional orthologous transcriptional regulator in B. thailandensis In this study, we showed that multiple glutamine amidotransferase 1 (GATase 1)-containing AraC family transcription regulators (GATRs) are involved in regulation of the B. thailandensis choline catabolic pathway (gbdR1, gbdR2, and souR). Using genetic analyses and sequencing the transcriptome in the presence and absence of choline, we identified the likely regulons of gbdR1 (BTH_II1869) and gbdR2 (BTH_II0968). We also identified a functional ortholog for P. aeruginosa souR, a GATR that regulates the metabolism of sarcosine to glycine. GbdR1 is absolutely required for expression of the choline catabolic locus, similar to P. aeruginosa GbdR, while GbdR2 is important to increase expression of the catabolic locus. Additionally, the B. thailandensis SouR ortholog (BTH_II0994) is required for catabolism of choline and its metabolites as carbon sources, whereas in P. aeruginosa, SouR function can by bypassed by GbdR. The strategy employed by B. thailandensis represents a distinct regulatory solution to control choline catabolism and thus provides both an evolutionary counterpoint and an experimental system to analyze the acquisition and regulation of this pathway during environmental growth and infection. IMPORTANCE: Many proteobacteria that occupy similar environmental niches have horizontally acquired orthologous genes for metabolism of compounds useful in their shared environment. The arrangement and differential regulation of these components can help us understand both the evolution of these systems and the potential roles these pathways have in the biology of each bacterium. Here, we describe the transcriptome response of Burkholderia thailandensis to the eukaryote-enriched molecule choline, identify the regulatory pathway governing choline catabolism, and compare the pathway to that previously described for Pseudomonas aeruginosa These data support a multitiered regulatory network in B. thailandensis, with conserved orthologs in the select agents Burkholderia pseudomallei and Burkholderia mallei, as well as the opportunistic lung pathogens in the Burkholderia cepacia clade. PMID- 27381917 TI - Regulation of Ribosomal Protein Operons rplM-rpsI, rpmB-rpmG, and rplU-rpmA at the Transcriptional and Translational Levels. AB - It is widely assumed that in the best-characterized model bacterium Escherichia coli, transcription units encoding ribosomal proteins (r-proteins) and regulation of their expression have been already well defined. However, transcription start sites for several E. coli r-protein operons have been established only very recently, so that information concerning the regulation of these operons at the transcriptional or posttranscriptional level is still missing. This paper describes for the first time the in vivo regulation of three r-protein operons, rplM-rpsI, rpmB-rpmG, and rplU-rpmA The results demonstrate that transcription of all three operons is subject to ppGpp/DksA-dependent negative stringent control under amino acid starvation, in parallel with the rRNA operons. By using single copy translational fusions with the chromosomal lacZ gene, we show here that at the translation level only one of these operons, rplM-rpsI, is regulated by the mechanism of autogenous repression involving the 5' untranslated region (UTR) of the operon mRNA, while rpmB-rpmG and rplU-rpmA are not subject to this type of regulation. This may imply that translational feedback control is not a general rule for modulating the expression of E. coli r-protein operons. Finally, we report that L13, a primary protein in 50S ribosomal subunit assembly, serves as a repressor of rplM-rpsI expression in vivo, acting at a target within the rplM translation initiation region. Thus, L13 represents a novel example of regulatory r-proteins in bacteria. IMPORTANCE: It is important to obtain a deeper understanding of the regulatory mechanisms responsible for coordinated and balanced synthesis of ribosomal components. In this paper, we highlight the major role of a stringent response in regulating transcription of three previously unexplored r-protein operons, and we show that only one of them is subject to feedback regulation at the translational level. Improved knowledge of the regulatory pathways controlling ribosome biogenesis may promote the development of novel antibacterial agents. PMID- 27381918 TI - The ChrSA and HrrSA Two-Component Systems Are Required for Transcriptional Regulation of the hemA Promoter in Corynebacterium diphtheriae. AB - Corynebacterium diphtheriae utilizes heme and hemoglobin (Hb) as iron sources for growth in low-iron environments. In C. diphtheriae, the two-component signal transduction systems (TCSs) ChrSA and HrrSA are responsive to Hb levels and regulate the transcription of promoters for hmuO, hrtAB, and hemA ChrSA and HrrSA activate transcription at the hmuO promoter and repress transcription at hemA in an Hb-dependent manner. In this study, we show that HrrSA is the predominant repressor at hemA and that its activity results in transcriptional repression in the presence and absence of Hb, whereas repression of hemA by ChrSA is primarily responsive to Hb. DNA binding studies showed that both ChrA and HrrA bind to the hemA promoter region at virtually identical sequences. ChrA binding was enhanced by phosphorylation, while binding to DNA by HrrA was independent of its phosphorylation state. ChrA and HrrA are phosphorylated in vitro by the sensor kinase ChrS, whereas no kinase activity was observed with HrrS in vitro Phosphorylated ChrA was not observed in vivo, even in the presence of Hb, which is likely due to the instability of the phosphate moiety on ChrA. However, phosphorylation of HrrA was observed in vivo regardless of the presence of the Hb inducer, and genetic analysis indicates that ChrS is responsible for most of the phosphorylation of HrrA in vivo Phosphorylation studies strongly suggest that HrrS functions primarily as a phosphatase and has only minimal kinase activity. These findings collectively show a complex mechanism of regulation at the hemA promoter, where both two-component systems act in concert to optimize expression of heme biosynthetic enzymes. IMPORTANCE: Understanding the mechanism by which two-component signal transduction systems function to respond to environmental stimuli is critical to the study of bacterial pathogenesis. The current study expands on the previous analyses of the ChrSA and HrrSA TCSs in the human pathogen C. diphtheriae The findings here underscore the complex interactions between the ChrSA and HrrSA systems in the regulation of the hemA promoter and demonstrate how the two systems complement one another to refine and control transcription in the presence and absence of Hb. PMID- 27381919 TI - Single-Stranded DNA Uptake during Gonococcal Transformation. AB - Neisseria gonorrhoeae is naturally competent for transformation. The first step of the transformation process is the uptake of DNA from the environment into the cell. This transport step is driven by a powerful molecular machine. Here, we addressed the question whether this machine imports single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) at similar rates. The fluorescence signal associated with the uptake of short DNA fragments labeled with a single fluorescent marker molecule was quantified. We found that ssDNA with a double stranded DNA uptake sequence (DUS) was taken up with a similar efficiency as dsDNA. Imported ssDNA was degraded rapidly, and the thermonuclease Nuc was required for degradation. In a nuc deletion background, dsDNA and ssDNA with a double-stranded DUS were imported and used as the substrates for transformation, whereas the import and transformation efficiencies of ssDNA with single-stranded DUS were below the detection limits. We conclude that the DNA uptake machine requires a double-stranded DUS for efficient DNA recognition and transports ssDNA and dsDNA with comparable efficiencies. IMPORTANCE: Bacterial transformation enables bacteria to exchange genetic information. It can speed up adaptive evolution and enhances the potential of DNA repair. The transport of DNA through the outer membrane is the first step of transformation in Gram-negative species. It is driven by a powerful molecular machine whose mechanism remains elusive. Here, we show for Neisseria gonorrhoeae that the machine transports single- and double-stranded DNA at comparable rates, provided that the species-specific DNA uptake sequence is double stranded. Moreover, we found that single-stranded DNA taken up into the periplasm is rapidly degraded by the thermonuclease Nuc. We conclude that the secondary structure of transforming DNA is important for the recognition of self DNA but not for the process of transport through the outer membrane. PMID- 27381921 TI - How Mohs Surgery Transformed Into a First-Line Treatment of Skin Cancer. AB - Mohs surgery is considered ideal treatment for many types of skin cancers. Developed by Dr Frederic Edward Mohs (1910-2002), Mohs surgery allows all surgical margins to be viewed microscopically, ensuring no cancer cells go unremoved, yet it failed to achieve immediate acceptance when first introduced in the 1940s. A catalyst to the widespread acceptance of Mohs surgery occurred with the work of dermatologic colleagues who reported excellent results without using the paste. It suggested the real innovation of Mohs surgery lay in its microscopic control and not the paste, the discontinuation of which removed all the problems associated with its use. PMID- 27381920 TI - The Last r Locus Unveiled: T4 RIII Is a Cytoplasmic Antiholin. AB - The latent period of phage T4, normally ~25 min, can be extended indefinitely if the infected cell is superinfected after 5 min. This phenomenon, designated lysis inhibition (LIN), was first described in the 1940s and is genetically defined by mutations in diverse T4 r genes. RI, the main effector of LIN, has been shown to be secreted to the periplasm, where, upon activation by superinfection with a T even virion, it binds to the C-terminal periplasmic domain of the T4 holin T and blocks its lethal permeabilization of the cytoplasmic membrane. Another r locus, rIII, has been the subject of conflicting reports. In this study, we show that RIII, an 82-amino-acid protein, is also required for LIN in both Escherichia coli B strains and E. coli K-12 strains. In T4DeltarIII infections, LIN was briefly established but was unstable. The overexpression of a cloned rIII gene alone impeded T-mediated lysis temporarily. However, coexpression of rIII and rI resulted in a stable LIN state. Bacterial two-hybrid assays and pulldown assays showed that RIII interacts with the cytoplasmic N terminus of T, which is a critical domain for holin function. We conclude that RIII is a T4 antiholin that blocks membrane hole formation by interacting directly with the holin. Accordingly, we propose an augmented model for T4 LIN that involves the stabilization of a complex of three proteins in two compartments of the cell: RI interacting with the C terminus of T in the periplasm and RIII interacting with the N terminus of T in the cytoplasm. IMPORTANCE: Lysis inhibition is a unique feature of phage T4 in response to environmental conditions, effected by the antiholin RI, which binds to the periplasmic domain of the T holin and blocks its hole-forming function. Here we report that the T4 gene rIII encodes a cytoplasmic antiholin that, together with the main antiholin, RI, inhibits holin T by forming a complex of three proteins spanning two cell compartments. PMID- 27381923 TI - Preparation of 3-azoindoles and 3-hydrazonoindolin-2-imines as well as their applications as NNO pincer ligands for boron. AB - Potassium carbonate-promoted coupling reactions between 3-diazoindolin-2-imines and nucleophiles were tested. By respectively applying 2-naphthalenols and 2 arylacetates as nucleophiles, 3-azoindoles and 3-hydrazonoindolin-2-imines were obtained in excellent yields. Moreover, 3-azoindol-2-amines could be used as NNO pincer ligands for boron and resulted in the formation of hexacycleborofluorides with their absorption around 580 nm in dichloromethane. PMID- 27381922 TI - HBsAg mutations related to occult hepatitis B virus infection in HIV-positive patients result in a reduced secretion and conformational changes of HBsAg. AB - BACKGROUND: Occult hepatitis B infection (OBI) is a frequent finding in human immunodeficiency virus (HIV)-infected patients. While several related mutations in the hepatitis B virus (HBV) genome have been reported, their distinct impact on HBsAg synthesis is largely obscure. METHODS: Thirty-one (18%) out of 172 HIV infected patients, who were selected from HBsAg-negative patients, were positive for HBV-DNA assigned as being OBI-positive. We generated a series of expression constructs of variant HBsAg with "a" determinant amino acid substitutions including P127L, P127T, S136Y, and P127T + S136Y using site-directed mutagenesis. The expression of variant HBsAg was examined by transient transfection in hepatoma cells, followed by HBsAg immunoassay and immunofluorescence stained with specific anti-HBs antibodies. The potential impact of amino acid substitutions at different positions for conformational changes in the HBsAg was investigated using bioinformatics. RESULTS: All variants comprising either single or combined mutations resulted in significantly reduced HBsAg detection in supernatants and in cell lysates of hepatoma cells transfected with the constructs. Moreover, intracellular immunofluorescence staining of cytoblocks showed perinuclear and cytoplasmic fluorescence of HBsAg constructs with significantly diminished fluorescent intensity in comparison to the wild type. Altered protein conformations by predictive models, indicating an impaired detection by the host's immune response as well as by commercial antibody-based test assays. CONCLUSION: Mutations in the "a" determinant region of HBV as often found in OBI remarkably impair the detection of HBsAg from serum and infected cells, emphasizing the relevance of alternative methods such as HBV-DNA quantification for high-risk groups like HIV-infected individuals. J. Med. Virol. 89:246-256, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27381924 TI - Mucosal mast cells are indispensable for the timely termination of Strongyloides ratti infection. AB - Mast cells and basophils are innate immune cells with overlapping functions that contribute to anti-helminth immunity. Mast cell function during helminth infection was previously studied using mast cell-deficient Kit-mutant mice that display additional mast cell-unrelated immune deficiencies. Here, we use mice that lack basophils or mucosal and connective tissue mast cells in a Kit independent manner to re-evaluate the impact of each cell type during helminth infection. Neither mast cells nor basophils participated in the immune response to tissue-migrating Strongyloides ratti third-stage larvae, but both cell types contributed to the early expulsion of parasitic adults from the intestine. The termination of S. ratti infection required the presence of mucosal mast cells: Cpa3Cre mice, which lack mucosal and connective tissue mast cells, remained infected for more than 150 days. Mcpt5Cre R-DTA mice, which lack connective tissue mast cells only, and basophil-deficient Mcpt8Cre mice terminated the infection after 1 month with wild-type kinetics despite their initial increase in intestinal parasite burden. Because Cpa3Cre mice showed intact Th2 polarization and efficiently developed protective immunity after vaccination, we hypothesize that mucosal mast cells are non-redundant terminal effector cells in the intestinal epithelium that execute anti-helminth immunity but do not orchestrate it. PMID- 27381925 TI - Regulation of intestinal homeostasis by the ulcerative colitis-associated gene RNF186. AB - Genome-wide association studies and subsequent deep sequencing analysis have identified susceptible loci for inflammatory bowel diseases (IBDs) including ulcerative colitis (UC). A gene encoding RING finger protein 186 (RNF186) is located within UC-susceptible loci. However, it is unclear whether RNF186 is involved in IBD pathogenesis. Here, we show that RNF186 controls protein homeostasis in colonic epithelia and regulates intestinal inflammation. RNF186, which was highly expressed in colonic epithelia, acted as an E3 ligase mediating polyubiquitination of its substrates. Permeability of small organic molecules was augmented in the intestine of Rnf186-/- mice. Increased expression of several RNF186 substrates, such as occludin, was found in Rnf186-/- colonic epithelia. The disturbed protein homeostasis in Rnf186-/- mice correlated with enhanced endoplasmic reticulum (ER) stress in colonic epithelia and increased sensitivity to intestinal inflammation after dextran sulfate sodium (DSS) treatment. Introduction of an UC-associated Rnf186 mutation led to impaired E3 ligase activity and increased sensitivity to DSS-induced intestinal inflammation in mice. Thus, RNF186 maintains gut homeostasis by controlling ER stress in colonic epithelia. PMID- 27381927 TI - Funding PrEP for HIV prevention. PMID- 27381926 TI - Treatment outcomes and lessons learned from 5134 cases of outpatient office-based endovascular procedures in a vascular surgical practice. AB - Introduction The office-based endovascular facility has increased in number recently due in part to expedient patient experience. This study analyzed treatment outcomes of procedures performed in our office-based endovascular suite. Methods Treatment outcomes of 5134 consecutive procedures performed in our office-based endovascular suites from 2006 to 2013 were analyzed. Five sequential groups (group I-V) of 1000 consecutive interventions were compared with regard to technical success and treatment outcomes. Results Our patients included 2856 (56%) females and 2267 (44%) males. Procedures performed included diagnostic arteriogram, arterial interventions, venous interventions, dialysis access interventions, and venous catheter management, which were 1024 (19.9%), 1568 (30.6%), and 3073 (60.0%), 621(12.1%), and 354 (6.9%), respectively. The complication rates for group I, II, III, IV, and V were 3%, 1.5%, 1%, 1.1%, and 0.7%, respectively. The complication rate was higher in group I when compared to each of the remaining four groups ( p < 0.05). Nine patients (0.18%) died within the 30-day period following their procedures, and none were procedure related. Conclusions Endovascular procedure can be performed safely in an office-based facility with excellent outcomes. Lessons learned in establishing office-based endovascular suites with efforts to reduce procedural complications and optimize quality patient care are discussed. PMID- 27381929 TI - Neural response to modulating the probability that actions of self or other result in auditory tones: A parametric fMRI study into causal ambiguity. AB - In normal circumstances we can easily distinguish between changes to the external world brought about by our own actions from those with external causes. However, in certain contexts our sense of ownership and agency over acts is not so clear. Neuroimaging studies have implicated a number of regions in the sense of agency, some of which have been shown to vary continuously with action-outcome discordance. However, little is known about dynamic, ambiguous contexts characterised by a lack of information for self-other differentiation, yet such ambiguous states are important in relation to symptoms and levels of consciousness that characterise certain mental health conditions. With a block design fMRI paradigm, we investigated neural responses to changes in the probability that a participant's irregular finger taps over 12s would result in auditory tones as opposed to tones generated by 'another's finger taps'. The main findings were that misattribution increased in ambiguous conditions where the probability of a tone belonging to self and other was equal. Task-sensitive brain regions, previously identified in self-agency, motor cognition, and ambiguity processing, showed a quadratic response to our self-to-other manipulation, with particular sensitivity to self-control. Task performance (low error and bias) was related to attenuated response in ambiguous conditions while increased response in regions associated with the default mode network was associated with greater overall error and bias towards other. These findings suggest that causal ambiguity as it occurs over time is a prominent feature in sense of agency, one that may eventually contribute to a more comprehensive understanding of positive symptoms of psychosis. PMID- 27381928 TI - Effects of two dominance manipulations on the stress response: Cognitive and embodied influences. AB - In response to stress, physiological and mental resources are allocated towards those systems that are needed for rapid responding in terms of fight or flight. On the other hand, long term regenerative processes such as growth, digestion and reproduction are attenuated. Levels of the sex steroid testosterone are reduced in participants that suffer from chronic stress. However, beyond its role for reproductive functions, testosterone plays an important role in the regulation of social status and dominance, testosterone levels increase during competition or when the social status is challenged. The Trier Social Stress Test (TSST), a laboratory stressor with a substantial social-evaluative component, can provoke an increase in salivary testosterone levels. Still, so far the reported findings regarding acute stress effects on testosterone are equivocal, possibly due to moderating effects. In this study we experimentally manipulated social dominance in 56 healthy participants (28m) by two independent manipulations (body posture and cognitive role taking) and subjected them to the TSST. We analyzed salivary testosterone and cortisol levels as dependent measures for the endocrine stress response. The role taking manipulation interacted with the testosterone response: we found the strongest increase when participants had to put themselves in a dominant (vs. submissive) role. Our results suggest that transient changes in testosterone levels during stress reflect a response to status threat that is affected by social dominance. PMID- 27381930 TI - Helping from the heart: Voluntary upregulation of heart rate variability predicts altruistic behavior. AB - Our various daily activities continually require regulation of our internal state. These regulatory processes covary with changes in High Frequency Heart Rate Variability (HF-HRV), a marker of parasympathetic activity. Specifically, incidental increases in HF-HRV accompany positive social engagement behavior and prosocial action. Little is known about deliberate regulation of HF-HRV and the role of voluntary parasympathetic regulation in prosocial behavior. Here, we present a novel biofeedback task that measures the ability to deliberately increase HF-HRV. In two large samples, we find that a) participants are able to voluntarily upregulate HF-HRV, and b) variation in this ability predicts individual differences in altruistic prosocial behavior, but not non-altruistic forms of prosociality, assessed through 14 different measures. Our findings suggest that self-induction of parasympathetic states is involved in altruistic action. The biofeedback task may provide a measure of deliberate parasympathetic regulation, with implications for the study of attention, emotion, and social behavior. PMID- 27381931 TI - Early averted gaze processing in the right Fusiform Gyrus: An EEG source imaging study. AB - Humans are able to categorize face properties with impressively short latencies. Nevertheless, the latency at which gaze recognition occurs is still a matter of debate. Through spatio-temporal analysis of high-density event-related potentials (ERP), we investigated the brain activity underlying the ability to spontaneously and quickly process gaze. We presented neutral faces with direct and averted gaze in a matching picture paradigm, where subjects had to detect repetition of identical faces and gaze was implicitly manipulated. The results indicate that faces with averted gaze were better discriminated than faces with direct gaze, and evoked stronger P100 amplitudes localized to the right fusiform gyrus. In contrast, direct gaze induced stronger activation in the orbital frontal gyrus at this latency. Later in time, at the beginning of the N170 component, direct gaze induced changes in scalp topography with a stronger activation in the right medial temporal gyrus. The location of these differential activations of direct vs. averted gaze further support the view that faces with averted gaze are perceived as less rewarding than faces with direct gaze. We additionally found differential ERP responses between repeated and novel faces as early as 50ms, thereby replicating earlier studies of very fast detection of mnestic aspects of stimuli. Together, these results suggest an early dissociation between implicit gaze detection and explicit identity processing. PMID- 27381932 TI - Thinking Out of the Box to Increase Technical Success in Fenestrated and Branched Endovascular Aneurysm Repair. PMID- 27381933 TI - Complete Ipsilateral Femoral Approach Using an Iliac Branch Device to Preserve a Sole Internal Iliac Artery After Aortic Stent-Graft Placement. AB - PURPOSE: To report implantation of an iliac branch device (IBD) for preserving antegrade blood flow to a sole internal iliac artery (IIA) via an ipsilateral approach during endovascular repair to reline an aortobi-iliac allograft. TECHNIQUE: The technique is described in a 55-year-old man with an enteric fistula involving an aortobi-iliac Y-prosthesis. After complete excision, the prosthesis was replaced by an allograft. Due to rebleeding and resuturing of the graft, total stent-graft relining of the allograft was planned with preservation of the sole left IIA using an iliac side branch (ZBIS). During introduction of a 12-F sheath over the allograft's neobifurcation to establish a femorofemoral through-and-through approach, the allograft ruptured. A compliant balloon was inflated to control the hemorrhage. The IBD was first fully deployed, followed by stent-graft relining. Consequently, stent-graft implantation in the left IIA using a crossover maneuver was no longer feasible, so a 0.035-inch super stiff wire was introduced through the IBD's 20-F sheath. A 12-mm semi-compliant balloon was inflated in the common iliac artery above the iliac branch to act as an abutment for a 7-F sheath to run over the stiff wire into the IIA for delivery/deployment of a stent-graft. CONCLUSION: It is feasible to use a complete ipsilateral femoral approach for IBD implantation after aortic stent graft placement. PMID- 27381934 TI - Multilayer Flow Modulator Treatment of Abdominal and Thoracoabdominal Aortic Aneurysms With Side Branch Coverage: Outcomes From a Prospective Single-Center Moroccan Registry. AB - PURPOSE: To evaluate endovascular repair of thoracoabdominal aortic aneurysms (TAAA) and abdominal aortic aneurysms (AAA) using the Multilayer Flow Modulator (MFM) in high-surgical-risk patients with at least one covered branch vessel. METHODS: In this prospective single-center nonrandomized trial, 18 patients (mean age 61.1 years; 16 men) with TAAA (n=10, mean diameter 74.4 mm) and AAA (n=8, mean diameter 67.8 mm) were treated with the MFM between June 2009 and September 2012. The primary safety endpoints were all-cause mortality at 30 days and 12 months and neurological complications. The primary efficacy endpoint was overall procedure success, defined as patency of covered branch vessels, reductions in aneurysm diameter, and sac thrombus formation. RESULTS: The technical success rate was 100% (53 study devices implanted, mean stented length 273 mm). Through mean follow-up of 13.4 months, all 61 covered branch vessels remained patent; there were no neurologic complications, ruptures, or instances of device migration, kinking, or fracture. Three patients died, 2 of unrelated causes and one of an undetermined cause. Only one reintervention with an additional MFM implanted at 5 years was required for a type I endoleak in a young patient with natural growth. Carefully planned and executed diameter and volume measurements demonstrated aneurysm shrinkage and progressive sac thrombus formation for both patient groups. CONCLUSION: Through midterm follow-up, treatment of high-surgical risk TAAA and AAA patients with the MFM appears to be safe and effective, maintaining branch vessel patency and reducing rupture risk through reduction of aneurysm diameter and modulation of flow dynamics. Longer term follow-up is needed. PMID- 27381935 TI - Can Parenting Intervention Prevent Cascading Effects From Placement Instability to Insecure Attachment to Externalizing Problems in Maltreated Toddlers? AB - Multiple placement changes disrupt continuity in caregiving and undermine well being in children in child welfare. This study conducted secondary data analysis of a randomized controlled trial to examine whether a relationship-based intervention, Promoting First Relationships((c)) (PFR), reduced risk for a maladaptive cascade from placement instability to less secure attachment to elevated externalizing problems. Participants included caregivers (birth or foster/kin) of toddlers (10-24 months) recently transitioned to their care because of child welfare placement decisions. Although main effects of PFR on security and externalizing problems were not previously observed, this study's results revealed that PFR attenuated the association between multiple placement changes (baseline) and less security (postintervention) and that the indirect effect of placement instability on greater externalizing problems (6-month follow up) via less security was evident only in toddlers in the comparison condition. These findings shed light on how a history of multiple caregiver changes may influence toddlers' risk for poor adjustment in subsequent placements, and the promise of supporting caregivers through a parenting intervention to prevent such risk. PMID- 27381937 TI - The role of the neutrophil Fcgamma receptor I (CD64) index in diagnosing spontaneous bacterial peritonitis in cirrhotic patients. AB - OBJECTIVE: To investigate the role of the neutrophil Fcgamma receptor I (CD64) index in the diagnosis of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. METHODS: A total of 123 cirrhotic patients with ascites who fulfilled the inclusion criteria were enrolled in this study. Ascites and blood samples were collected; the polymorphonuclear neutrophil (PMN) count, bacterial culture, and related laboratory tests were performed. The CD64 index was determined for each sample using flow cytometry. RESULTS: The neutrophil CD64 index results were significantly higher in cirrhotic patients with SBP than in those without SBP (p<0.001). There was a positive correlation between the neutrophil CD64 index and the PMN count in ascites. In the receiver operating characteristic curve (ROC) analysis, the area under the curve (AUC) was 0.894 (95% confidence interval 0.823 0.964, p<0.001). The optimal cut-off value for the neutrophil CD64 index was 2.02. The sensitivity and specificity of the neutrophil CD64 index for cirrhotic patients with SBP were 80.49% and 93.90%, respectively. The elevated neutrophil CD64 index was down-regulated by antibiotic therapy (p=0.002). CONCLUSIONS: The neutrophil CD64 index could be used as a sensitive and specific indicator for the diagnosis of SBP in cirrhotic patients with ascites and is also modulated by antibiotic therapy. PMID- 27381936 TI - Use of evidence based practices to improve survival without severe morbidity for very preterm infants: results from the EPICE population based cohort. AB - OBJECTIVES: To evaluate the implementation of four high evidence practices for the care of very preterm infants to assess their use and impact in routine clinical practice and whether they constitute a driver for reducing mortality and neonatal morbidity. DESIGN: Prospective multinational population based observational study. SETTING: 19 regions from 11 European countries covering 850 000 annual births participating in the EPICE (Effective Perinatal Intensive Care in Europe for very preterm births) project. PARTICIPANTS: 7336 infants born between 24+0 and 31+6 weeks' gestation in 2011/12 without serious congenital anomalies and surviving to neonatal admission. MAIN OUTCOME MEASURES: Combined use of four evidence based practices for infants born before 28 weeks' gestation using an "all or none" approach: delivery in a maternity unit with appropriate level of neonatal care; administration of antenatal corticosteroids; prevention of hypothermia (temperature on admission to neonatal unit >=36 degrees C); surfactant used within two hours of birth or early nasal continuous positive airway pressure. Infant outcomes were in-hospital mortality, severe neonatal morbidity at discharge, and a composite measure of death or severe morbidity, or both. We modelled associations using risk ratios, with propensity score weighting to account for potential confounding bias. Analyses were adjusted for clustering within delivery hospital. RESULTS: Only 58.3% (n=4275) of infants received all evidence based practices for which they were eligible. Infants with low gestational age, growth restriction, low Apgar scores, and who were born on the day of maternal admission to hospital were less likely to receive evidence based care. After adjustment, evidence based care was associated with lower in-hospital mortality (risk ratio 0.72, 95% confidence interval 0.60 to 0.87) and in-hospital mortality or severe morbidity, or both (0.82, 0.73 to 0.92), corresponding to an estimated 18% decrease in all deaths without an increase in severe morbidity if these interventions had been provided to all infants. CONCLUSIONS: More comprehensive use of evidence based practices in perinatal medicine could result in considerable gains for very preterm infants, in terms of increased survival without severe morbidity. PMID- 27381938 TI - Non-invasive assessment of liver fibrosis by magnetic resonance elastography in patients with congenital heart disease undergoing the Fontan procedure and intracardiac repair. AB - BACKGROUND: The incidence of late liver complications such as fibrosis or cirrhosis has increased among patients who have undergone the Fontan procedure. Magnetic resonance elastography (MRE) recently emerged as a technique to clinically evaluate liver fibrosis. However, few reports have described its use in evaluating liver fibrosis in children with congenital heart disease (CHD). METHODS AND RESULTS: Fifty-seven children were examined and divided into four groups: 27 with CHD who underwent intracardiac repair (ICR); 16 with CHD who underwent the Fontan procedure (Fontan); 14 in a control group (control); and two with cirrhosis (cirrhosis). Liver stiffness (LS) was measured using MRE. Other assessments included central venous pressure (CVP) as determined by cardiac catheterization. Circulating biomarker levels were also determined. There were no significant differences in biomarker levels among the groups. However, the LS degree was significantly higher in the Fontan group than in the control group. On stepwise multivariate analysis, only the CVP level was a statistically significant independent predictor of LS. There was also a strong correlation between LS and CVP and between LS and time interval since Fontan surgery. CONCLUSIONS: This study clearly demonstrated that LS was significantly increased after the Fontan procedure and that CVP was a predictor of LS. MRE is a highly sensitive tool that can evaluate liver fibrosis in children who undergo the Fontan procedure and enable earlier detection of LS than biomarkers. PMID- 27381939 TI - Indications and outcomes of excimer laser coronary atherectomy: Efficacy and safety for thrombotic lesions-The ULTRAMAN registry. AB - BACKGROUND: Excimer laser coronary atherectomy (ELCA) recently became available in Japan, but ELCA's effectiveness and safety are not clear. METHODS AND RESULTS: We enrolled consecutive patients who underwent ELCA and were registered in the Utility of Laser for Transcatheter Atherectomy-Multicenter Analysis around Naniwa (ULTRAMAN) registry comprising six Japanese medical centers around Naniwa in Japan with patients registered from April 2006 to June 2015. We evaluated the catheter sizes used and compared the success rate, thrombolysis in myocardial infarction (TIMI) flow, blush score, and complications between the rich-thrombus (RT) group [acute coronary syndrome (ACS) and saphenous vein graft (SVG)] and the poor-thrombus (PT) group [in-stent restenosis (ISR), chronic total occlusion (CTO), calcification, and long or bifurcation (L&B) lesions]. Of the 328 patients, 6 (1.8%) were treated for an SVG, 175 (53.4%) were treated for ACS, 18 (5.5%) for CTO, 106 (32.4%) for ISR, 8 (2.4%) for calcification, and 15 for L&B lesions (4.6%). A 1.7-mm (concentric)-diameter ELCA catheter was used most frequently (59.4%). High success rates were achieved in both the RT and PT groups, but the TIMI flow grade and blush score were significantly lower and the complications rate was significantly higher in the RT group (n=181). CONCLUSIONS: In Japan, the major indications for ELCA have been ACS and ISR. ELCA can provide a safe and effective treatment even for RT lesions. PMID- 27381940 TI - Relative roles of land- and ocean-atmosphere interactions in Asian-Pacific thermal contrast variability at the precessional band. AB - In a 250-kyr transient simulation of the Community Earth System Model (CESM), we identified a precessional forced seesaw of the summer middle-upper tropospheric eddy temperature between Asia and the North Pacific as the paleo-APO (Asian Pacific oscillation). The paleo-APO variability is out of phase with the precession parameter. Corresponding to a positive paleo-APO phase, both the subtropical anticyclonic circulation over the North Pacific and the East Asian summer monsoon (EASM) strengthen. Summer anomalous sea surface temperature shows a western cold-eastern warm pattern over the extratropical North Pacific and a zonal positive-negative-positive pattern over the tropical Pacific. The variations in the simulated paleo-APO and East Asian southerly wind at the precessional band agree well with the geological proxies at the Dongge, Sanbao, Linzhu, and Hulu caves in China, which also implies that these proxies may well reflect the variability in the southerly wind over East Asia. Sensitivity experiments further reveal that the reduced precession parameter may enhance the positive paleo-APO phase and the associated EASM because of the response of the land-atmosphere interactions to the precessional insolation changes. The effect of the ocean-atmosphere interactions on the paleo-APO is secondary. PMID- 27381941 TI - Spherulization as a process for the exudation of chemical cues by the encrusting sponge C. crambe. AB - Ecological interactions in the marine environment are now recognized to be partly held by chemical cues produced by marine organisms. In particular, sponges are sessile animals thought to rely on the bioactive substances they synthesize to ensure their development and defense. However, the mechanisms leading the sponges to use their specialized metabolites as chemical cues remain unknown. Here we report the constant release of bioactive polycyclic guanidinic alkaloids by the Mediterranean sponge Crambe crambe into the dissolved and the particulate phases using a targeted metabolomics study. These compounds were proven to be stored into already described specialized (spherulous) sponge cells and dispersed into the water column after release through the sponge exhaling channels (oscula), leading to a chemical shield surrounding the sponge. Low concentrations of these compounds were demonstrated to have teratogenic effects on embryos of a common sea squirt (ascidian). This mechanism of action called spherulization may therefore contribute to the ecological success of encrusting sponges that need to extend their substrate cover to expand. PMID- 27381942 TI - Polarization domain wall pulses in a microfiber-based topological insulator fiber laser. AB - Topological insulators (TIs), are novel two-dimension materials, which can act as effective saturable absorbers (SAs) in a fiber laser. Moreover, based on the evanescent wave interaction, deposition of the TI on microfiber would create an effective SA, which has combined advantages from the strong nonlinear optical response in TI material together with the sufficiently-long-range interaction length in fiber taper. By using this type of TI SA, various scalar solitons have been obtained in fiber lasers. However, a single mode fiber always exhibits birefringence, and hence can support two orthogonal degenerate modes. Here we investigate experimentally the vector characters of a TI SA fiber laser. Using the saturated absorption and the high nonlinearity of the TI SA, a rich variety of dynamic states, including polarization-locked dark pulses and their harmonic mode locked counterparts, polarization-locked noise-like pulses and their harmonic mode locked counterparts, incoherently coupled polarization domain wall pulses, including bright square pulses, bright-dark pulse pairs, dark pulses and bright square pulse-dark pulse pairs are all observed with different pump powers and polarization states. PMID- 27381944 TI - Effect of nonalcoholic steatohepatitis on renal filtration and secretion of adefovir. AB - BACKGROUND AND AIMS: Adefovir, an acyclic nucleotide reverse transcriptase inhibitor used to treat hepatitis B viral infection, is primarily eliminated renally through cooperation of glomerular filtration with active tubular transport. Nonalcoholic steatohepatitis is a variable in drug disposition, yet the impact on renal transport processes has yet to be fully understood. The goal of this study was to determine the effect of nonalcoholic steatohepatitis on the pharmacokinetics of adefovir in rats given a control or methionine and choline deficient diet to induce nonalcoholic steatohepatitis. METHODS: Animals received a bolus dose of 7mg/kg (35MUCi/kg) [(3)H] adefovir with consequent measurement of plasma and urine concentrations. Inulin clearance was used to determine glomerular filtration rate. RESULTS: Methionine and choline deficient diet induced nonalcoholic steatohepatitis prolonged the elimination half-life of adefovir. This observation occurred in conjunction with reduced distribution volume and hepatic levels of adefovir. Notably, despite these changes, renal clearance and overall clearance were not changed, despite markedly reduced glomerular filtration rate in nonalcoholic steatohepatitis. Alteration of glomerular filtration rate was fully compensated for by a significant increase in tubular secretion of adefovir. Analysis of renal transporters confirmed transcriptional up-regulation of Mrp4, the major transporter for adefovir tubular secretion. CONCLUSIONS: This study demonstrates changes to glomerular filtration and tubular secretion that alter pharmacokinetics of adefovir in nonalcoholic steatohepatitis. Nonalcoholic steatohepatitis-induced changes in renal drug elimination processes could have major implications in variable drug response and the potential for toxicity. PMID- 27381943 TI - Platinum-containing compound platinum pyrithione is stronger and safer than cisplatin in cancer therapy. AB - DNA is the well-known molecular target of current platinum-based anticancer drugs; consequently, their clinical use is severely restricted by their systemic toxicities and drug resistance originating from non-selective DNA damage. Various strategies have been developed to circumvent the shortcomings of platinum-based chemotherapy but the inherent problem remains unsolved. Here we report that platinum pyrithione (PtPT), a chemically well-characterized synthetic complex of platinum, inhibits proteasome function and thereby exhibits greater and more selective cytotoxicity to multiple cancer cells than cisplatin, without showing discernible DNA damage both in vitro and in vivo. Moreover, unlike the classical proteasome inhibitor bortezomib/Velcade which inhibits the proteasome via blocking the peptidase activity of 20S proteasomes, PtPT primarily deactivates 26S proteasome-associated deubiquitinases USP14 and UCHL5. Furthermore, PtPT can selectively induce cytotoxicity and proteasome inhibition in cancer cells from leukemia patients but not peripheral blood mononuclear cells from healthy humans. In nude mice, PtPT also remarkably inhibited tumor xenograft growth, without showing the adverse effects that were induced by cisplatin. Hence, we have discovered a new platinum-based anti-tumor agent PtPT which targets 26S proteasome-associated deubiquitinases rather than DNA in the cell and thereby exerts safer and more potent anti-tumor effects, identifying a highly translatable new platinum-based anti-cancer strategy. PMID- 27381945 TI - HIV information needs of parents of young men who have sex with men. AB - OBJECTIVE: Young men who have sex with men (YMSM) have unique health concerns, including high rates of HIV infection. To prevent HIV, YMSM need credible information from trusted sources, specifically parents. Little is known about what health information resources parents of YMSM need to communicate with their child about HIV prevention. The primary objective of this study was to examine the proxy health information seeking behaviours of parents of YMSM and to identify information resources that parents need to communicate with their YMSM identified child about HIV prevention. METHODS: Qualitative findings were grouped into four categories: parents' current health information sources; barriers to seeking health information; parents' health information needs; and recommendations for delivery of health information for parents. Ten in-depth interviews were conducted with parents of YMSM. RESULTS: Parents reported consulting physicians and the Internet for HIV/AIDS information. They reported finding limited information targeted towards parents of YMSM and provided suggestions for improving the delivery of health information including training, websites and the local news. CONCLUSIONS: Delivery of tailored HIV prevention information to parents may be effective in helping combat HIV among YMSM. Given that YMSM bear the greatest burden for HIV, this study highlights the need to include parents of YMSM in future interventions aimed at reducing YMSM's risk of HIV/AIDS. PMID- 27381946 TI - High Thermal Gradient in Thermo-electrochemical Cells by Insertion of a Poly(Vinylidene Fluoride) Membrane. AB - Thermo-Electrochemical cells (Thermocells/TECs) transform thermal energy into electricity by means of electrochemical potential disequilibrium between electrodes induced by a temperature gradient (DeltaT). Heat conduction across the terminals of the cell is one of the primary reasons for device inefficiency. Herein, we embed Poly(Vinylidene Fluoride) (PVDF) membrane in thermocells to mitigate the heat transfer effects - we refer to these membrane-thermocells as MTECs. At a DeltaT of 12 K, an improvement in the open circuit voltage (Voc) of the TEC from 1.3 mV to 2.8 mV is obtained by employment of the membrane. The PVDF membrane is employed at three different locations between the electrodes i.e. x = 2 mm, 5 mm, and 8 mm where 'x' defines the distance between the cathode and PVDF membrane. We found that the membrane position at x = 5 mm achieves the closest internal ?T (i.e. 8.8 K) to the externally applied DeltaT of 10 K and corresponding power density is 254 nWcm(-2); 78% higher than the conventional TEC. Finally, a thermal resistivity model based on infrared thermography explains mass and heat transfer within the thermocells. PMID- 27381947 TI - Redefining the "carrier" state for foot-and-mouth disease from the dynamics of virus persistence in endemically affected cattle populations. AB - The foot-and-mouth disease virus (FMDV) "carrier" state was defined by van Bekkum in 1959. It was based on the recovery of infectious virus 28 days or more post infection and has been a useful construct for experimental studies. Using historic data from 1,107 cattle, collected as part of a population based study of endemic FMD in 2000, we developed a mixed effects logistic regression model to predict the probability of recovering viable FMDV by probang and culture, conditional on the animal's age and time since last reported outbreak. We constructed a second set of models to predict the probability of an animal being probang positive given its antibody response in three common non-structural protein (NSP) ELISAs and its age. We argue that, in natural ecological settings, the current definition of a "carrier" fails to capture the dynamics of either persistence of the virus (as measured by recovery using probangs) or the uncertainty in transmission from such animals that the term implies. In these respects it is not particularly useful. We therefore propose the first predictive statistical models for identifying persistently infected cattle in an endemic setting that captures some of the dynamics of the probability of persistence. Furthermore, we provide a set of predictive tools to use alongside NSP ELISAs to help target persistently infected cattle. PMID- 27381948 TI - Development of depression and deterioration in quality of life in German dental medical students in preclinical semesters. AB - PURPOSE: Early intervention to counter mental disorders during the course of studies in dentistry is indicated in view of the pronounced prevalence of burnout in this student collective. To assess the proportion of students in whom these risk states can be quantified in measurable parameters for concrete mental disorders, we conducted surveys among students of dental medicine during the first 2.5 years of their studies. METHODS: We surveyed a total of 163 students of dental medicine in their first 5 semesters of study. Standardized, validated psychological questionnaires on depressive symptoms (Beck Depression Inventory; BDI-II) and mental and physical quality of life (Short Form Survey; SF-12) were used in the survey, with per-semester participant quotas of around 90%. RESULTS: Regarding depression, the students were within the range of the normal populace at the beginning of the 1st semester. Symptoms of depression then became more pronounced with every succeeding semester. In the fifth semester, the average levels determined were equivalent to a depression with a clinical treatment indication. Hardly any change was registered for physical wellbeing in the quality of life questionnaire. The mental sum scores, however, reflected dramatic downturns in quality of life. Highly significant correlations between the parameters described here - depressivity and mental quality of life - were observed in all semesters. CONCLUSION: The participating students begin their course of studies at the level of the average populace for the symptoms surveyed, then develop, on average, a clinically manifest depression after 2.5 years. The personal experience of a deterioration of mental quality of life appears to be crucial in the phenomena observed. PMID- 27381949 TI - Prehospital Endotracheal Intubation in Warm Climates: Caution is Required. AB - BACKGROUND: Out-of-hospital endotracheal intubation is a frequent procedure for trauma care. Nevertheless, in warm climates, sunlight and heat can interfere with the flow of the usual procedure. They can affect the equipment and hinder the operator. There are few data on this issue. The presentation of this case highlights three common complications that may occur when intubating under a hot and bright sun. CASE REPORT: A 23-year-old man had a car accident in Djibouti, at 11:00 a.m., in broad sunlight. The heat was scorching. Due to a severe head trauma, with a Glasgow Coma Scale score of 8, it was decided to perform an endotracheal intubation. The operator faced three problems: the difficulty of seeing inside the mouth in the bright sunlight, the softening of the tube under the influence of the heat, and the inefficiency of colorimetric CO2 detectors in the warm atmosphere in confirming the proper endotracheal tube placement. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Solutions are simple, but must be known and planned ahead, prior to beginning the procedure: Putting a jacket over his head while doing the laryngoscopy would solve the problem of dazzle; adjuncts like a stylet or gum elastic bougie have to be used at the outset to fix the softening problem; alternative methods to exhaled CO2 detection, such as the syringe aspiration technique, to confirm the proper tube placement, should be available. PMID- 27381950 TI - A Case of Recalcitrant Urinary Tract Infection. PMID- 27381951 TI - Regarding Spontaneous Subdural Hematoma in a Middle-Aged Adult. PMID- 27381952 TI - Thinking and Training Together for Pediatric Emergency Care. PMID- 27381953 TI - Epidural Steroid Injection Complicated by Intrathecal Entry, Pneumocephalus, and Chemical Meningitis. AB - BACKGROUND: Epidural steroid injections are frequently used to treat back and extremity pain. The procedure is generally safe, with a low rate of adverse events, including intrathecal entry, pneumocephalus, and chemical meningitis. CASE REPORT: We report a case of a 45-year-old woman who presented to the emergency department (ED) with headache, nausea, vomiting, and photophobia after a lumbar epidural steroid injection. She was afebrile and had an elevated white blood cell count. A non-contrast computed tomography scan of the head revealed pneumocephalus within the subarachnoid space and lateral ventricles. The patient was admitted to the ED observation unit for pain control and subsequently developed a marked leukocytosis and worsening meningismus. A lumbar puncture was performed yielding cerebrospinal fluid (CSF) consistent with meningitis (1,000 total nucleated cells, 89% neutrophils, 85 mg/dL total protein, and no red blood cells). Gram stain revealed no bacteria. The patient was admitted on empiric vancomycin and ceftriaxone. Antibiotics were discontinued at 48 h when CSF cultures remained negative and the patient was clinically asymptomatic. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should consider intrathecal entry and pneumocephalus in patients who present with a headache after an epidural intervention. The management of pneumocephalus includes supportive therapies, appropriate positioning, and supplemental oxygen. These symptoms can be accompanied by fever, leukocytosis, and markedly inflammatory CSF findings consistent with bacterial or chemical meningitis. Empiric treatment with broad-spectrum antibiotics should be initiated until CSF culture results are available. PMID- 27381954 TI - The Flipped Classroom in Emergency Medicine Using Online Videos with Interpolated Questions. AB - BACKGROUND: Utilizing the flipped classroom is an opportunity for a more engaged classroom session. This educational approach is theorized to improve learner engagement and retention and allows for more complex learning during class. No studies to date have been conducted in the postgraduate medical education setting investigating the effects of interactive, interpolated questions in preclassroom online video material. OBJECTIVES: We created a flipped classroom for core pediatric emergency medicine (PEM) topics using recorded online video lectures for preclassroom material and interactive simulations for the in-classroom session. METHODS: Lectures were filmed and edited to include integrated questions on an online platform called Zaption. One-half of the residents viewed the lectures uninterrupted (Group A) and the remainder (Group B) viewed with integrated questions (2-6 per 5-15-min segment). Residents were expected to view the lectures prior to in-class time (total viewing time of approximately 21/2 h). The 21/2-h in-class session included four simulation and three procedure stations, with six PEM faculty available for higher-level management discussion throughout the stations. Total educational time of home preparation and in-class time was approximately 5 h. RESULTS: Residents performed better on the posttest as compared to the pretest, and their satisfaction was high with this educational innovation. In 2014, performance on the posttest between the two groups was similar. However, in 2015, the group with integrated questions performed better on the posttest. CONCLUSION: An online format combined with face-to-face interaction is an effective educational model for teaching core PEM topics. PMID- 27381955 TI - Reactive oxygen species derived from NADPH oxidase 1 and mitochondria mediate angiotensin II-induced smooth muscle cell senescence. AB - Cellular senescence has emerged as an important player in both physiology and pathology. Excessive reactive oxygen species (ROS) is known to mediate cellular senescence. NADPH oxidases are major sources for ROS production in the vascular wall; the roles of different NADPH oxidase isoforms in cellular senescence remain unclear, however. We investigated the roles of two NADPH oxidase isoforms in mitochondrial dysfunction during angiotensin II (Ang II)-induced cellular senescence of human aortic vascular smooth muscle cells (VSMCs). Ang II (10(-7)M) stimulated ROS generation, exhibiting early increases between 30 and 60min and sustained increases between 24h and 72h, and induced VSMCs senescence after 48h or 72h treatment as assessed with senescence-associated beta-galactosidase activity and the expression of two cell cycle inhibitors, p21 and p16. ROS scavengers and membrane-permeable catalase (catalase-PEG) reduced Ang II stimulated cellular senescence. Furthermore, small interfering RNA (siRNA) of NADPH oxidase catalytic subunit Nox1, but not that of another isoform Nox4, inhibited Ang II-induced cellular senescence. Nox1 siRNA inhibited both early and sustained ROS increases induced by Ang II. In addition, a mitochondrial-specific antioxidant, mitoQ10, effectively inhibited Ang II-induced ROS increases and cellular senescence. Ang II decreased ATP synthesis and induced mitochondrial membrane depolarization, which were attenuated by pre-treating cells with Nox1 siRNA, mitoQ10 or catalase-PEG. The effect of Ang II on the mitochondrial regulator peroxisome-proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and its downstream genes was examined. Ang II stimulated S570 phosphorylation of PGC-1alpha with concomitant decreases in catalase and uncoupling protein-2 (UCP-2) levels between 12h and 72h, which were inhibited by Nox1 siRNA. Knockdown of both catalase and UCP-2 mimicked Ang II-induced VSMC senescence. These results suggested that Ang II-stimulated Nox1 activation mediates mitochondrial dysfunction, probably by decreasing PGC-1alpha activity and increasing mitochondrial oxidative stress, and leads to cellular senescence of VSMCs. PMID- 27381957 TI - A Reappraisal of Prediabetes. PMID- 27381956 TI - Inhibitory control in obesity and binge eating disorder: A systematic review and meta-analysis of neurocognitive and neuroimaging studies. AB - The ability to exercise appropriate inhibitory control is critical in the regulation of body weight, but the exact mechanisms are not known. In this systematic review, we identified 37 studies that used specific neuropsychological tasks relevant to inhibitory control performance in obese participants with and without binge eating disorder (BED). We performed a meta-analysis of the studies that used the stop signal task (N=8). We further examined studies on the delay discounting task, the go/no-go task and the Stroop task in a narrative review. We found that inhibitory control is significantly impaired in obese adults and children compared to individuals with body weight within a healthy range (Standardized Mean Difference (SMD): 0.30; CI=0.00, 0.59, p=0.007). The presence of BED in obese individuals did not impact on task performance (SMD: 0.05; CI: 0.22, 0.32, p=0.419). Neuroimaging studies in obesity suggest that lower prefrontal cortex activity affects inhibitory control and BMI. In summary, impairment in inhibitory control is a critical feature associated with obesity and a potential target for clinical interventions. PMID- 27381958 TI - Resistance to Thyroid Hormone alpha-Emerging Definition of a Disorder of Thyroid Hormone Action. PMID- 27381959 TI - The Model T. PMID- 27381960 TI - Disorders of Puberty: Take a Good History! PMID- 27381963 TI - Eyewitness recall and suggestibility in individuals with Down syndrome. AB - BACKGROUND: Many criminal justice professionals perceive the eyewitness skills of individuals with intellectual disabilities to be weaker than those of typically developing (TD) individuals. Down syndrome (DS) is one of the most common genetic causes of intellectual disabilities, yet there is no research addressing eyewitness skills in this population. This study examined the eyewitness recall and suggestibility of young people with DS. METHOD: Young people with DS and mental age-matched TD children viewed a video of a non-violent petty crime and were subsequently asked to freely recall the event before being asked general and specific questions incorporating both misleading and non-leading prompts. RESULTS: Compared with mental age-matched TD individuals, young people with DS produced as much information, were just as accurate and were no more suggestible. CONCLUSIONS: The eyewitness memory skills of young people with DS are comparable to those of mental age-matched TD children. The implications of these findings for the forensic context and eyewitness memory are discussed. PMID- 27381964 TI - The role of vitamin D, obesity and physical exercise in regulation of glycemia in Type 2 Diabetes Mellitus patients. AB - AIM: The aims of this study were to determine the role of vitamin D, obesity and physical exercise in the regulation of glycemia in Type 2 Diabetes Mellitus patients in a highly consanguineous population. DESIGN: Case and control study. SETTING: The survey was carried out at the Hamad General Hospital and Primary Health Care (PHC) centers in the State of Qatar. SUBJECTS: The study was conducted from November 2012 to June 2014 among subjects above 30 years of age. Of the 2224 registered with diagnosed diabetes and free diseases attending Hamad General Hospital and PHC centers agreed and gave their consent to study. METHODS: Questionnaire included socio-demographic variables, body mass index (BMI), consanguinity, lifestyle habits, family history of diabetes, blood pressure and development of diabetes complications such as retinopathy, nephropathy, and neuropathy were collected at regular intervals throughout the follow-up. Univariate and multivariate statistical analysis were performed. RESULTS: There were statistically significant difference between patients with diabetic and control in terms of ethnicity (p=0.012), level of education (p=0.002), occupation (p<0.001), monthly income (p<0.001), BMI(p=0.024), sport activity (p=0.018), cigarette smoking (p<0.001), consanguinity (p=0.029) and family history of Diabetes Mellitus (p<0.001) and co-morbidity hypertension (p=0.041). Further, the biochemistry values in the studied subjects with T2DM compared to healthy controls and the study revealed that serum Vitamin D, BMI, fasting glucose level, calcium, HbA1c, total cholesterol HDL, LDL, bilirubin, triglycerides, uric acid and blood pressure systolic and diastolic were higher in T2DM compared to their counterparts. Multivariate logistic regression showed that vitamin D deficiency ng/mL, Family History of T2DM, BMI (kg/m2) hypertension, consanguinity, income, mother occupation, ethnicity, educational level and Lack of physical exercise variables were significant predictors of diabetes. In the group of Diabetes Mellitus Type 2 patients, 39.3% as opposed to 51.2% in the control group had vitamin D deficiency, 25(OH) D3 levels<=10ng/ml (p<0.001). In the group of Diabetes Mellitus Type 2 patients, 34.6% as opposed to 37.9% in the control group had vitamin D insufficiency, 25(OH)D3 levels <20ng/ml (p < 0.001). In the group of Diabetes Mellitus Type 2 patients, 22.8% as opposed to 14.2% in the control group had vitamin D sufficiency, 25(OH)D3 levels >30 10ng/ml (p < 0.001). CONCLUSION: Vitamin D, family history of diabetes, consanguinity marriages' and hereditary gene-environment interactions and physical exercise may also contribute to the current diabetes epidemic in Qatari's Arab populations. PMID- 27381966 TI - Vascular phenotype of obese adolescents with prediabetes and/or Type 2 diabetes (T2DM): Review of the current literature. PMID- 27381965 TI - Serum uric acid level as a determinant of the metabolic syndrome: A case control study. AB - AIMS: To determine whether elevations of uric acid levels are associated with the cluster of disorders described in metabolic syndrome and to evaluate whether hyperuricemia may be considered a component of this syndrome. METHODS: One year case-control study was conducted in Bikaner, Rajasthan, India from January to December 2013. The study population consisted of 200 subjects, 100 with metabolic syndrome (case) and 100 without metabolic syndrome (control) aged between 18 and 80 years, attending OPD at PBM Hospital were studied. Controls were age and sex matched to the cases. Blood tests and all physical variables were examined using standard methods. Subjects were divided into 6 groups according to their possession of 0, 1, 2, 3, 4 or 5 components of the metabolic syndrome. Statistical analysis was done using ANOVA, linear regression analysis and multivariate linear regression model. RESULTS: Mean serum UA level was significantly associated with all components of metabolic syndrome (p<0.001) and had strong positive correlation (r=+0.66 to +0.77, p<0.0001) with all of them except serum HDL with which it showed strong negative correlation(r=-0.71, p<0.0001). It increased as the number of metabolic factors increased showing a highly significant trend (p<0.0001). On multivariate regression analysis UA contributed to 66.84% variance of metabolic syndrome. CONCLUSION: The current multivariate regression analysis clearly infers that uric acid can be considered as a marker and potential modifier of metabolic syndrome. PMID- 27381967 TI - Study of association between beverage consumption pattern and lipid profile in shift workers. AB - AIMS: The circadian system influences on health and metabolic function that can cause raising some risk factor of metabolic syndrome. Few studies have examined data that incorporate the full complexity of daily beverage intake pattern on lipid profiles. The purpose of this study was to investigate relation between daily water and beverage intake of adults working in day or shift work and lipid profile. MATERIALS AND METHODS: Total beverages intake was estimated in shift and administrative staff of Ahvaz International Airport, Iran. Forty five male, aged 25-55 years, attending this institute were invited to participate in this study. They completed a three-day food records and all participants were measured plasma lipid profiles. RESULTS AND CONCLUSION: Forty one of participants completed all aspects of the study. Two clusters were emerged, labeled descriptively as Conventional including "high Sugar-sweetened drinkers" and "low sugar drinkers". The highest intake of water was in cluster 1 (1170.9ml/day) even this amount is much less than the daily recommended amounts. There were significant differences in triglyceride levels among day and night shift workers. According to the results, there is inadequacy of water and high sugar beverage intake among the shift workers which it is a potential risk of some related chronic diseases such as metabolic syndrome with high triglyceride level in the future. PMID- 27381968 TI - Effect of weight loss on renal function in overweight and obese patients with heart failure. AB - AIMS: The effect of intentional weight loss on glomerular filtration rate (GFR) in overweight and obese patients with heart failure (HF), diabetes mellitus (DM) and/or metabolic syndrome (MS) has not been studied. The purpose of the present study is to assess the short term effects of intentional weight loss on renal function in this population. MATERIALS AND METHODS: Fifty nine patients were recruited to participate in a 3-month intensive behavioral weight management intervention and received one of two standard structured energy-restricted meal plans (1200 or 1500kcal/day) based on their computed calorie deficit. Weight and renal function (serum creatinine, BUN and estimated glomerular filtration rate based on two formulas - Modification in Renal Disease Study (MDRD), and modified version of Cockcroft-Gault formula reported by Salazar Corcoran for obese patients (absolute and relative formulas) - were evaluated at baseline and at 3 months. RESULTS: Participants had eGFR in the normal range at baseline and lost an average of 7.56+/-14.9 pounds (p<0.0001) over 3 months; however, there was no significant reduction in serum creatinine, BUN or eGFR. CONCLUSION: This study provides evidence that intentional weight loss in overweight and obese patients with HF along with DM, and/or MS and normal baseline renal function does not adversely affect renal function overtime. PMID- 27381969 TI - Metabolic syndrome and new onset diabetes after kidney transplantation. AB - AIMS: The metabolic syndrome developed after kidney transplantation is the result of several factors which are identical with the risk factors in normal population, however, also some factors typical for the transplanted patients especially the effects of immunosuppressive therapy. MATERIAL AND METHODS: In the groupof 268 patients after kidney transplantation, which had no type 1 or type 2 diabetes mellitus before transplantation, we identified patients with metabolic syndrome(based on IDF criteria), 12 months from the kidney transplantation. In all patients, we recorded the following parameters: age at the time of transplantation, type of immunosuppression, waist measure, the value of triacylglycerols, the value of HDL cholesterol, presence of arterial hypertension, andthe value of glycaemia in fasting state (or presence of diabetes mellitus). The groupof patients was divided into the control group and the group of patients with metabolic syndrome. RESULTS: The average age of patients was 46.1+/-11.6years. The control group included 149 patients (55.6%),and we identified the metabolicsyndromein 119patients (44.4%). The patients with metabolicsyndrome were significantly older (P<0.0001), had significantly larger waist (both the entiregroup and the males andfemales) P<0.0001.The femaleswith metabolic syndrome had significantly lower value of HDL-cholesterol (P=0.0013), and significantly higher number of patients with metabolic syndrome had hyperglycaemia in fasting state or diabetes mellitus (P=0.0006). CONCLUSION: By controlling the weight and waist, we may identify the risk patients for development of metabolic syndrome after kidney transplantation. PMID- 27381970 TI - Red Cell Distribution Width in Obstructive Sleep Apnea. AB - INTRODUCTION: Red cell distribution width (RDW) describes heterogeneity in the size of red blood cells. An increase in RDW has been associated with excess mortality in heart failure and other chronic diseases. Since there is an increased risk of cardiovascular morbidity and mortality in obstructive sleep apnea (OSA), it is possible that these patients have a high RDW. METHOD: We recruited subjects aged 18 to 60 years referred to the sleep-disordered breathing unit for suspected OSA. Subjects with any comorbidity were excluded. Apnea hypopnea index (AHI) was calculated from the respiratory polygraphy. The RDW was obtained from the complete blood count. Changes in RDW after one year of treatment with continuous positive airway pressure (CPAP) were determined. RESULTS: We included 34 healthy subjects and 138 with OSA, aged 40.5+/-9.8 and 45.6+/-9.2 (P=.004) years, respectively. The RDW was higher in subjects with OSA compared to healthy subjects: 13.40 (12.40 to 14.40) vs. 13.15 (12.07 to 14.23) (P=.036). AHI showed a positive independent relationship with RDW in both the whole population (r=0.223; P=.002) and the OSA group (r=0.231; P=.005). No significant changes were found in RDW after one year of CPAP therapy. CONCLUSIONS: RDW increase in patients with OSA is directly associated with severity, although levels are not modified by the effective treatment of OSA with CPAP. PMID- 27381971 TI - What has Changed in Community-Acquired Pneumonia in Recent Years? PMID- 27381972 TI - Cardiac Metastases from A Lung Tumor. PMID- 27381973 TI - Sarcoid-Like Reaction with Mediastinal and Pulmonary Involvement in a Patient with Testicular Cancer. PMID- 27381974 TI - Ocular Hypertension Requiring Suspension of Inhaled Corticosteroids. PMID- 27381975 TI - Unusual Tracheobronchial Foreign Body. PMID- 27381976 TI - Hydroacenes Made Easy by Gold(I) Catalysis. AB - A novel strategy for the synthesis of partially saturated acene derivatives has been developed based on a Au(I) -catalyzed cyclization of 1,7-enynes. This method provides straightforward access to stable polycyclic products featuring the backbone of the acene series, up to nonacene. PMID- 27381977 TI - Online Obsessive-Compulsive Disorder Treatment: Preliminary Results of the "OCD? Not Me!" Self-Guided Internet-Based Cognitive Behavioral Therapy Program for Young People. AB - BACKGROUND: The development and evaluation of Internet-delivered cognitive behavioral therapy (iCBT) interventions provides a potential solution for current limitations in the acceptability, availability, and accessibility of mental health care for young people with obsessive-compulsive disorder (OCD). Preliminary results support the effectiveness of therapist-assisted iCBT for young people with OCD; however, no previous studies have examined the effectiveness of completely self-guided iCBT for OCD in young people. OBJECTIVE: We aimed to conduct a preliminary evaluation of the effectiveness of the OCD? Not Me! program for reducing OCD-related psychopathology in young people (12-18 years). This program is an eight-stage, completely self-guided iCBT treatment for OCD, which is based on exposure and response prevention. METHODS: These data were early and preliminary results of a longer study in which an open trial design is being used to evaluate the effectiveness of the OCD? Not Me! PROGRAM: Participants were required to have at least subclinical levels of OCD to be offered the online program. Participants with moderate-high suicide/self-harm risk or symptoms of eating disorder or psychosis were not offered the program. OCD symptoms and severity were measured at pre- and posttest, and at the beginning of each stage of the program. Data was analyzed using generalized linear mixed models. RESULTS: A total of 334 people were screened for inclusion in the study, with 132 participants aged 12 to 18 years providing data for the final analysis. Participants showed significant reductions in OCD symptoms (P<.001) and severity (P<.001) between pre- and posttest. CONCLUSIONS: These preliminary results suggest that fully automated iCBT holds promise as a way of increasing access to treatment for young people with OCD; however, further research needs to be conducted to replicate the results and to determine the feasibility of the program. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613000152729; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363654 (Archived by WebCite at http://www.webcitation.org/ 6iD7EDFqH). PMID- 27381978 TI - Bilirubin is an Endogenous Antioxidant in Human Vascular Endothelial Cells. AB - Bilirubin is a standard serum biomarker of liver function. Inexplicably, it is inversely correlated with cardiovascular disease risk. Given the role of endothelial dysfunction in originating cardiovascular diseases, direct analysis of bilirubin in the vascular endothelium would shed light on these relationships. Hence, we used high-performance liquid chromatography coupled with thermal lens spectrometric detection and diode array detection for the determination of endogenous cellular IXalpha-bilirubin. To confirm the isomer IXalpha-bilirubin, we used ultra-performance liquid chromatography coupled with a high-resolution mass spectrometer using an electrospray ionization source, as well as tandem mass spectrometric detection. We measured bilirubin in both arterial and venous rat endothelium (0.9-1.5 pmol mg(-1) protein). In the human endothelial Ea.hy926 cell line, we demonstrated that intracellular bilirubin (3-5 pmol mg(-1) protein) could be modulated by either extracellular bilirubin uptake, or by up-regulation of heme oxygenase-1, a cellular enzyme related to endogenous bilirubin synthesis. Moreover, we determined intracellular antioxidant activity by bilirubin, with EC50 = 11.4 +/- 0.2 nM, in the range of reported values of free serum bilirubin (8.5-13.1 nM). Biliverdin showed similar antioxidant properties as bilirubin. We infer from these observations that intra-endothelial bilirubin oscillates, and may thus be a dynamic factor of the endothelial function. PMID- 27381979 TI - Ketogenic diet prevents neuronal firing increase within the substantia nigra during pentylenetetrazole-induced seizure in rats. AB - The mechanism responsible for the anti-seizure effect of ketogenic diets is poorly understood. Because the substantia nigra pars reticulata (SNr) is a "gate" center for seizures, the aim of the present experiment was to evaluate if a ketogenic diet modifies the neuronal response of this nucleus when a seizure inducing drug is administered in rats. Two groups of rats were given a standard diet (group 1) or a ketogenic diet (group 2) for four weeks, then the threshold for seizure induction and the firing rate of putative GABAergic neurons within the SNr were evaluated with progressive infusion of pentylenetetrazole under general anesthesia. The results demonstrated that the ketogenic diet abolished the correlation between the firing rate response of SNr-neurons and the seizure threshold. This result suggests that the anti-seizure effect of ketogenic diets can be due to a decrease in reactivity of GABAergic SNr-neurons. PMID- 27381980 TI - Atorvastatin attenuates the antinociceptive tolerance of morphine via nitric oxide dependent pathway in male mice. AB - The development of morphine-induced antinociceptive tolerance limits its therapeutic efficacy in pain management. Atorvastatin, or competitive inhibitor of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase, is mainstay agent in hypercholesterolemia treatment. Beyond the cholesterol-lowering activity, exploration of neuroprotective properties of this statin indicates its potential benefit in central nervous disorders. The aim of the present study was to assess the effects of atorvastatin in development and expression of morphine-induced analgesic tolerance in male mice and probable involvement of nitric oxide. Chronic and acute treatment with atorvastatin 10 and 20mg/kg, respectively, could alleviate morphine tolerance in development and expression phases. Chronic co administration of nitric oxide synthase (NOS) inhibitors including L-NAME (non selective NOS inhibitor; 2mg/kg), aminoguanidine (selective inducible NOS inhibitor; 50mg/kg) and 7-NI (selective neuronal NOS inhibitor; 15mg/kg) with atorvastatin blocked the protective effect of atorvastatin in tolerance reversal. Moreover, reversing the atorvastatin effect was also observed in acute simultaneous treatment of L-NAME (5mg/kg) and aminoguanidine (100mg/kg) with atorvastatin. Co-treatment of guanylyl cyclase inhibitor, ODQ (chronic dose: 10mg/kg and acute dose: 20mg/kg) was associated with prevention of atorvastatin anti-tolerance properties. Our results revealed that the atorvastatin modulating role in morphine antinociceptive tolerance is mediated at least in part via nitric oxide in animal pain models of hot plate and tail flick. PMID- 27381981 TI - Boozy Nights and Violent Fights: Perceptions of Environmental Cues to Violence and Crime in Licensed Venues. AB - This article examines perceptions of environmental cues to crime, violence, and injuries in barroom settings, and how they differ between bar fight participants and non-participants. Bouncer friendliness, patron sex composition, and room temperature were chosen as experimental variables based on three criteria: (a) emerged as a theme in bar user focus groups, (b) unclear effects in the literature, and (c) policy relevant and easy to modify. These experimental variables were manipulated in written vignettes set in a bar. A three-part online questionnaire recorded 681 male university students' responses to questions on demographics, the experiment, drinking and clubbing habits, and the Snell Masculinity Scale. A 2 * 2 * 2 randomized independent groups factorial design with covariates was embedded in the questionnaire, measuring the effects of the experimental variables on bar users' perceived fear of victimization, likelihood and frequency of crime, venue preference, and perceived severity of injuries after accounting for prior bar fight participation and masculinity. Participants generally rated perceived fear of victimization, likelihood and frequency of crime, and severity of injuries to be highest when the bouncer was unfriendly, the temperature was hot, and patrons were majority male. Only main effects were significant ( p < .01). Masculinity scale responses were not related to participant perceptions. While fight participants (9.8% of the sample) and non participants had similar perceptions of the risk associated with certain environmental cues, fight participants were significantly (a) less fearful of victimization in settings they perceived as dangerous and (b) more willing to drink in any hypothetical venue. PMID- 27381982 TI - Protein kinase B (AKT) regulates SYK activity and shuttling through 14-3-3 and importin 7. AB - The Protein kinase B (AKT) regulates a plethora of intracellular signaling proteins to fine-tune signaling of multiple pathways. Here, we found that following B-cell receptor (BCR)-induced tyrosine phosphorylation of the cytoplasmic tyrosine kinase SYK and the adaptor BLNK, the AKT/PKB enzyme strongly induced BLNK (>100-fold) and SYK (>100-fold) serine/threonine phosphorylation (pS/pT). Increased phosphorylation promoted 14-3-3 binding to BLNK (37-fold) and SYK (2.5-fold) in a pS/pT-concentration dependent manner. We also demonstrated that the AKT inhibitor MK2206 reduced pS/pT of both BLNK (3-fold) and SYK (2.5 fold). Notably, the AKT phosphatase, PHLPP2 maintained the activating phosphorylation of BLNK at Y84 and increased protein stability (8.5-fold). In addition, 14-3-3 was required for the regulation SYK's interaction with BLNK and attenuated SYK binding to Importin 7 (5-fold), thereby perturbing shuttling to the nucleus. Moreover, 14-3-3 proteins also sustained tyrosine phosphorylation of SYK and BLNK. Furthermore, substitution of S295 or S297 for alanine abrogated SYK's binding to Importin 7. SYK with S295A or S297A replacements showed intense pY525/526 phosphorylation, and BLNK pY84 phosphorylation correlated with the SYK pY525/526 phosphorylation level. Conversely, the corresponding mutations to aspartic acid in SYK reduced pY525/526 phosphorylation. Collectively, these and previous results suggest that AKT and 14-3-3 proteins down-regulate the activity of several BCR-associated components, including BTK, BLNK and SYK and also inhibit SYK's interaction with Importin 7. PMID- 27381984 TI - Comment on "A comprehensive guide of remediation technologies for oil contaminated soil - Present works and future directions". PMID- 27381983 TI - Assessing physio-macromolecular effects of lactic acid on Zygosaccharomyces bailii cells during microaerobic fermentation. AB - The ability of Zygosaccharomyces bailii to grow at low pH and in the presence of considerable amounts of weak organic acids, at lethal condition for Saccharomyces cerevisiae, increased the interest in the biotechnological potential of the yeast. To understand the mechanism of tolerance and growth effect of weak acids on Z. bailii, we evaluated the physiological and macromolecular changes of the yeast exposed to sub lethal concentrations of lactic acid. Lactic acid represents one of the important commodity chemical which can be produced by microbial fermentation. We assessed physiological effect of lactic acid by bioreactor fermentation using synthetic media at low pH in the presence of lactic acid. Samples collected from bioreactors were stained with propidium iodide (PI) which revealed that, despite lactic acid negatively influence the growth rate, the number of PI positive cells is similar to that of the control. Moreover, we have performed Fourier Transform Infra-Red (FTIR) microspectroscopy analysis on intact cells of the same samples. This technique has been never applied before to study Z. bailii under this condition. The analyses revealed lactic acid induced macromolecular changes in the overall cellular protein secondary structures, and alterations of cell wall and membrane physico-chemical properties. PMID- 27381985 TI - Chemical and biological assessment of sediments and water of Khalid Khor, Sharjah, United Arab Emirates. AB - Water and sediments were collected on March 2013 and April 2014 from Khalid Khor creek area in United Arab Emirates to assess their quality parameters. The pH and alkalinity of the water samples were measured and their values were similar to those of shallow saltwater ecosystems. In addition, elemental analyses and organic compounds were done using Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES) and Gas Chromatography-Mass Spectroscopy (GC-MS), respectively. The concentration of heavy and trace metals in the water samples were within the acceptable limits except for lead which showed high values, while the concentrations of metals in the sediment samples were relatively high and ranged from 6517 to 13,768mg/kg. GC-MS analysis showed the presence of polyaromatic heterocyclic (PAHs) compounds in sediments near the shipping area and in amounts classified as highly carcinogenic; however, no polychlorinated biphenyls (PCB) were identified. Moreover, fecal bacterial contamination in water was detected in concentrations that range between 300 and 10,140 organisms/100mL. PMID- 27381986 TI - Restoration and source identification of polycyclic aromatic hydrocarbons after the Wu Yi San oil spill, Korea. AB - On January 31, 2014, an oil spill accident occurred in Yeosu, South Korea. A total 800-899kl of oil from the pipeline was spilled into the sea. After the oil spill, the KIOST (Korea Institute of Ocean Science & Technology) researched PAHs (polycyclic aromatic hydrocarbons) in various media, but sedimentary PAHs were not analyzed despite their longer persistency than in other media. Therefore, this study examined PAH levels in intertidal sediments around Gwangyang Bay and identified PAH sources using oil fingerprinting. PAH residual levels showed a dramatic decrease during the four months after the accident and then remained at a relatively constant level. Analysis through regression equations indicate that this study area is likely to be restored to the PAH levels prior to the accident. Furthermore, the source analysis and oil fingerprinting analysis showed that PAH contamination in this study was unlikely to have originated from the spilled oil. PMID- 27381987 TI - Controlling populations of invasive pygmy mussel (Xenostrobus securis) through citizen science and environmental DNA. AB - Early detection of dangerous exotic species is crucial for stopping marine invasions. The New Zealand pygmy mussel Xenostrobus securis is a problematic species in coasts of temperate regions in the northern hemisphere. In this study we have controlled a population of this invader that recently expanded in a north Iberian estuary with both a participatory approach involving researchers and citizens, and employing a sensitive eDNA-based tool to monitor the population expansion in the estuary. Results demonstrate successful eradication of pygmy mussels in the outer part of the estuary with citizen science and the practical utility of eDNA for controlling biological invasions. PMID- 27381988 TI - Blood selenium concentrations in female Pacific black brant molting in Arctic Alaska: Relationships with age and habitat salinity. AB - Blood samples collected from 81 female Pacific black brant (Branta bernicla nigricans) molting near Teshekpuk Lake, Alaska, were analyzed for selenium concentration. The concentration of selenium in blood of after second year (hatched two or more years ago) females (0.84MUg/g wet weight) was significantly greater than the concentration in second year (hatched the previous year) females (0.61MUg/g wet weight). The concentrations of selenium we found in blood of black brant were 1.5 to 2 times greater than baseline values typical of freshwater birds, but considerably lower than reported in other marine waterfowl sampled in Alaska. This finding may be attributable in part to the nearly exclusive herbivorous diet of black brant. No relationship was noted between blood selenium concentration and molting habitat salinity. We are unaware of any previous reports of blood selenium concentrations in black brant. PMID- 27381989 TI - The beta-cell burden index of food: A proposal. AB - The quantity and quality of dietary fat and/or carbohydrate may alter one or more of the basic components of the insulin-glucose system, which in turn affect the pathways leading to alterations in glucose homeostasis and, possibly, to cardiovascular disease. This viewpoint article, reviewing some of the currently available tools aiming at quantifying the impact of dietary carbohydrates on the glucose-insulin homeostatic loop, highlights the unmet need of a more thorough assessment of the complex interaction between dietary factors and the glucose insulin system. A novel index, the "beta-cell burden index", may turn out to be a valuable tool to quantify the role played by the diet in shaping the risk of type 2 diabetes, cardiovascular disease and other metabolic and degenerative disorders, ideally orienting their prevention with strategies based on dietary modifications. PMID- 27381990 TI - Disorders of glucose metabolism in Prader-Willi syndrome: Results of a multicenter Italian cohort study. AB - BACKGROUND AND AIMS: Prader-Willi syndrome (PWS) is characterized by a high incidence of altered glucose metabolism (AGM). However, epidemiological data on impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) are still discordant. METHODS AND RESULTS: We performed a multicenter study based on 274 PWS patients [144 females, aged 20.3 +/- 10.4 yrs (range: 8.1-50.1 years)] evaluating the prevalence for AGM in the entire group, and according to age (children <10 yrs; adolescents 10-18 yrs, and adults >18 yrs), Body Mass Index (BMI = kg/m(2)), gender, genotypes (deletion or uniparental disomy for chromosome 15), and GH therapy (GHT) (untreated, previously or currently treated). Altogether, AGM was detected in 67 (24.4%) of patients (0.7% IFG, 10.2% IGT, 13.5% T2DM). The prevalence of AGM was correlated to age (p = 0.001), BMI (p = 0.001) and HOMA-IR (p = 0.001). However, gender, genotype, and GHT did not influence AGM development in univariate analysis. These data were confirmed as positive predictors when inserted in a multivariate analysis model. CONCLUSION: This study is the first report on the prevalence of AGM in a large population of PWS. Overall, PWS subjects show a high prevalence of AGM that appears more common in obese and adult subjects. Our data confirm the main role of obesity on the individual metabolic risk clustering in PWS, and thus reinforce the concept that improvement in weight control remains the most important goal of any PWS treatment program. PMID- 27381991 TI - Adipose-Derived Mesenchymal Stem Cells Ameliorate Lipid Metabolic Disturbance in Mice. AB - : Adipose-derived mesenchymal stem cells (AD-MSCs) have been shown to ameliorate hyperglycemia in diabetic animals and individuals. However, little is known about whether AD-MSCs affect lipid metabolism. Here we have demonstrated for the first time that AD-MSC infusion can significantly suppress the increase in body weight and remarkably improve dyslipidemia in db/db obese mice and diet-induced obesity mice. Induction of white fat tissue "browning" and activation of adenosine monophosphate-activated protein kinase and its downstream hormone-sensitive lipase in adipose tissue contribute to the antiobesity and lipid-lowering effects. Thus, AD-MSC infusion holds great therapeutic potential for dyslipidemia and associated cardiovascular diseases. SIGNIFICANCE: Mesenchymal stem cells (MSCs) are considered one of the most promising types of stem cells for translational application because of their rich tissue sources, multilineage differentiation capacity, and easy amplification in vitro and unique immunobiological properties. This study demonstrated that adipose-derived MSCs (AD-MSCs) infusion can significantly suppress the increase in body weight and remarkably improve dyslipidemia in obese mice. Induction of white fat tissue "browning" and activation of adenosine monophosphate-activated protein kinase and its downstream hormone-sensitive lipase in adipose tissue were demonstrated to contribute to the antiobesity and lipid-lowering effects. Thus, AD-MSC infusion holds great therapeutic potential for dyslipidemia. PMID- 27381992 TI - Concise Review: Functional Definition of Endothelial Progenitor Cells: A Molecular Perspective. AB - : : Since the discovery of endothelial progenitor cells (EPCs) almost 2 decades ago, there has been great hope in their use in treating chronic ischemic disease. Unfortunately, to date, many of the clinical trials using EPCs have been hampered by the lack of clear definition of this cell population. Attributes of a progenitor population are self-renewal and multipotentiality. Major progress has been achieved moving from a definition of EPCs based on a candidate cell surface molecule to a functional definition based essentially on self-renewal hierarchy of endothelial colony-forming cells (ECFCs). More recent work has seized on this functional characterization to associate gene expression signatures with the self renewal capacity of ECFCs. In particular, Notch signaling driving the quiescence of progenitors has been shown to be central to progenitor self-renewal. This new molecular definition has tremendous translational consequences, because progenitors have been shown to display greater vasculogenic potential. Also, this molecular definition of EPC self-renewal allows assessment of the quality of presumed EPC preparations. This promises to be the initial stage in progressing EPCs further into mainstream clinical use. SIGNIFICANCE: The development of a therapy using endothelial progenitor cells provides great hope for patients in treating cardiovascular diseases going forward. For continual development of this therapy toward the clinical, further understanding of the fundamental biology of these cells is required. This will enable a greater understanding of their stemness capacity and provide insight into their ability to differentiate and drive tissue regeneration when injected into a host. PMID- 27381993 TI - Concise Review: Markers for Assessing Human Stem Cell-Derived Implants as beta Cell Replacement in Type 1 Diabetes. AB - : : A depleted beta-cell mass causes diabetes complications that cannot be avoided by insulin administration. beta-Cell replacement can stop their development when restoring insulin's homeostatic role. This requires a sufficient number and an adequate functional state of the beta cells, together defined as "functional beta-cell mass." Intraportal implants of human pancreatic islet cells correct hyperglycemia in patients with type 1 diabetes, but this effect is transient and often incomplete. Studies to improve outcome are hindered by shortage in donor pancreases. Human pluripotent stem cells are a candidate source for mass production of grafts for beta-cell replacement. Their in vitro differentiation to pancreatic endoderm (stage 4) and to beta-cell-containing preparations (stage 7) provides grafts that generate beta-cell implants in mice. In vivo markers indicated a better outcome of device-encapsulated stage 4 cells and microencapsulated stage 7 cells as compared with nonencapsulated grafts. Encapsulation also offers the advantage of representative implant retrieval for direct analysis by ex vivo markers. Combination of in vitro, in vivo, and ex vivo markers allows comparison of different stem cell-derived grafts and implants, with each other and with clinical islet cell preparations that serve as reference. Data in mice provide insights into the biology of stem cell-generated beta-cell implants, in particular their capacity to establish and sustain a functional beta-cell mass. They can thus be indicative for translation of a graft to similar studies in patients, where metabolic benefit will be an additional marker of primordial importance. SIGNIFICANCE: Human stem cell-derived preparations can generate insulin-producing implants in immune-incompetent mice. Steps are undertaken for translation to patients with type 1 diabetes. Their therapeutic significance will depend on their capacity to establish a functional beta-cell mass that provides metabolic benefit. This study proposes the combined use of in vitro, in vivo, and ex vivo markers to assess this potential in preclinical models and in clinical studies. PMID- 27381995 TI - Airway compromising an airway. PMID- 27381994 TI - Neural substrates predicting short-term improvement of tinnitus loudness and distress after modified tinnitus retraining therapy. AB - Although tinnitus retraining therapy (TRT) is efficacious in most patients, the exact mechanism is unclear and no predictor of improvement is available. We correlated the extent of improvement with pre-TRT quantitative electroencephalography (qEEG) findings to identify neural predictors of improvement after TRT. Thirty-two patients with debilitating tinnitus were prospectively enrolled, and qEEG data were recorded before their initial TRT sessions. Three months later, these qEEG findings were correlated with the percentage improvements in the Tinnitus Handicap Inventory (THI) scores, and numeric rating scale (NRS) scores of tinnitus loudness and tinnitus perception. The THI score improvement was positively correlated with the pre-treatment activities of the left insula and the left rostral and pregenual anterior cingulate cortices (rACC/pgACC), which control parasympathetic activity. Additionally, the activities of the right auditory cortices and the parahippocampus, areas that generate tinnitus, negatively correlated with improvements in loudness. Improvements in the NRS scores of tinnitus perception correlated positively with the pre-TRT activities of the bilateral rACC/pgACC, areas suggested to form the core of the noise-canceling system. The current study supports both the classical neurophysiological and integrative models of tinnitus; our results serve as a milestone in the development of precision medicine in the context of TRT. PMID- 27381996 TI - Salmonella spondylodiscitis of the thoracic vertebrae mimicking spine tuberculosis. AB - Extraintestinal Salmonella infection involving the thoracic spine is very rare. It commonly presents with non-specific chronic back pain and can occur with no gastrointestinal manifestation. Blood test results and imaging findings are often indistinguishable from more common chronic spine infections such as spine tuberculosis. Culture studies remain the key to establishing a definitive diagnosis and subsequently successful treatment. We report a case in which a patient presented with symptoms and signs suggestive of spine tuberculosis, yet the culture examination revealed otherwise. PMID- 27381997 TI - Hypopyon uveitis following panretinal photocoagulation. AB - We report the case of a 58-year-old man with proliferative diabetic retinopathy in both eyes, and a history of recurrent anterior uveitis in the right eye, who underwent panretinal laser photocoagulation (PRP) for the retinopathy in both eyes, following which he developed hypopyon uveitis in the right eye. The condition was managed with topical steroids and cycloplegics, to which he readily responded. The case highlights that there is a breakdown of the blood aqueous barrier consequent to PRP. Patients with a history of uveitis are predisposed to develop recurrent uveitis after the said procedure and should be closely watched for such complications. PMID- 27381998 TI - Post binder radiography in pelvic trauma. PMID- 27382000 TI - Management of Depression in Patients With Cancer: A Clinical Practice Guideline. AB - PURPOSE: This report updates the Cancer Care Ontario Program in Evidence-Based Care guideline for the management of depression in adult patients with cancer. This guideline covers pharmacologic, psychological, and collaborative care interventions, with a focus on integrating practical management tools to assist clinicians in delivering appropriate treatments for depression in patients with cancer. METHODS: Recommendations were developed by synthesizing information from extant guidelines and reviews and searching for randomized controlled trials from the date of database inception (1964 for MEDLINE and 1974 for EMBASE) to January 2015. Quality assessment of guidelines and systematic reviews were conducted by using the Appraisal of Guidelines for Research and Evaluation II (AGREE II), Assessment of Multiple Systematic Reviews (AMSTAR), and Cochrane Risk of Bias tools. Final recommendations were developed through a standardized Program in Evidence-Based Care multidisciplinary expert and knowledge user review process. RESULTS: Two high-quality relevant clinical practice guidelines, eight pharmacologic trials, nine psychological trials, and eight collaborative care intervention trials composed the evidence base upon which the recommendations were developed. Eight specific recommendations were made to establish a standard of care for the management of depression in patients with cancer. The recommendations and practical management tools were reviewed as being well organized and helpful, although systemic barriers to implementation were identified. CONCLUSION: This updated guideline supports the previous general recommendation that patients with cancer who have depression may benefit from psychological and/or pharmacologic interventions, without evidence for the superiority of any specific treatment over another. New recommendations for a collaborative care model that incorporates a stepped care approach suggest that multidisciplinary mental health care restructuring may be required for optimal management of depression. PMID- 27381999 TI - Malagasy Genetic Ancestry Comes from an Historical Malay Trading Post in Southeast Borneo. AB - Malagasy genetic diversity results from an exceptional protoglobalization process that took place over a thousand years ago across the Indian Ocean. Previous efforts to locate the Asian origin of Malagasy highlighted Borneo broadly as a potential source, but so far no firm source populations were identified. Here, we have generated genome-wide data from two Southeast Borneo populations, the Banjar and the Ngaju, together with published data from populations across the Indian Ocean region. We find strong support for an origin of the Asian ancestry of Malagasy among the Banjar. This group emerged from the long-standing presence of a Malay Empire trading post in Southeast Borneo, which favored admixture between the Malay and an autochthonous Borneo group, the Ma'anyan. Reconciling genetic, historical, and linguistic data, we show that the Banjar, in Malay-led voyages, were the most probable Asian source among the analyzed groups in the founding of the Malagasy gene pool. PMID- 27382001 TI - Electronic Release of Pathology and Radiology Results to Patients: Opinions and Experiences of Oncologists. AB - PURPOSE: There is an emerging standard to provide patients rapid electronic access to elements of their medical records. Although surveys of patients generally support it, this practice is controversial among oncologists, because few empiric data are available for scenarios of potentially life-threatening conditions like cancer. We report the views of oncologists about patient electronic access to radiology and pathology results that could potentially indicate disease progression. METHODS: Four months before oncologists were surveyed, final results of radiology/pathology reports were routinely made available to patients online through a secure portal after a 7-day, hold to provide clinicians time to review and communicate results with the patients. Mixed methods were used to assess physician attitudes and experiences toward this change. RESULTS: One hundred twenty-nine oncologists were surveyed, and 82 (64%) responded. A small majority (54%) responded that the release of reports was somewhat or very beneficial for patients who received normal radiology/pathology results before discussion with a physician, but 87% said it was somewhat or very harmful for patients to receive abnormal results before discussion. Forty-nine percent reported that release of reports had a somewhat or very negative impact on communication with their patients. CONCLUSION: Almost half of oncologists reported that sharing digital radiology and pathology records had a negative impact on their communication with patients. Patient surveys in similar cancer populations would complement the physician perspective. Efforts are needed to improve consensus among oncologists and patients on how to best communicate such results in a timely fashion. PMID- 27382002 TI - Better Screening Using Big Data. PMID- 27382004 TI - World Health Organization. PMID- 27382003 TI - Neuroinflammation in animal models of traumatic brain injury. AB - Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. Neuroinflammation is prominent in the short and long-term consequences of neuronal injuries that occur after TBI. Neuroinflammation involves the activation of glia, including microglia and astrocytes, to release inflammatory mediators within the brain, and the subsequent recruitment of peripheral immune cells. Various animal models of TBI have been developed that have proved valuable to elucidate the pathophysiology of the disorder and to assess the safety and efficacy of novel therapies prior to clinical trials. These models provide an excellent platform to delineate key injury mechanisms that associate with types of injury (concussion, contusion, and penetration injuries) that occur clinically for the investigation of mild, moderate, and severe forms of TBI. Additionally, TBI modeling in genetically engineered mice, in particular, has aided the identification of key molecules and pathways for putative injury mechanisms, as targets for development of novel therapies for human TBI. This Review details the evidence showing that neuroinflammation, characterized by the activation of microglia and astrocytes and elevated production of inflammatory mediators, is a critical process occurring in various TBI animal models, provides a broad overview of commonly used animal models of TBI, and overviews representative techniques to quantify markers of the brain inflammatory process. A better understanding of neuroinflammation could open therapeutic avenues for abrogation of secondary cell death and behavioral symptoms that may mediate the progression of TBI. PMID- 27382005 TI - Pathogenesis and Risk Factors for Cerebral Infarct After Surgical Aortic Valve Replacement. AB - BACKGROUND AND PURPOSE: Stroke is a potentially devastating complication of cardiac surgery. Identifying predictors of radiographic infarct may lead to improved stroke prevention for surgical patients. METHODS: We reviewed 129 postoperative brain magnetic resonance imagings from a prospective study of patients undergoing surgical aortic valve replacement. Acute infarcts were classified as watershed or embolic using prespecified criteria. RESULTS: Acute infarct on magnetic resonance imaging was seen in 79 of 129 patients (61%), and interrater reliability for stroke pathogenesis was high (kappa=0.93). Embolic infarcts only were identified in 60 patients (46%), watershed only in 2 (2%), and both in 17 (13%). In multivariable logistic regression, embolic infarct was associated with aortic arch atheroma (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.0-12.0; P=0.055), old subcortical infarcts (OR, 5.5; 95% CI, 1.1 26.6; P=0.04), no history of percutaneous transluminal coronary angioplasty or coronary artery bypass graft (OR, 4.0; 95% CI, 1.2-13.7; P=0.03), and higher aortic valve gradient (OR, 1.3 per 5 mm Hg; 95% CI, 1.09-1.6; P=0.004). Watershed infarct was associated with internal carotid artery stenosis >=70% (OR, 11.7; 95% CI, 1.8-76.8; P=0.01) and increased left ventricular ejection fraction (OR, 1.6 per 5% increase; 95% CI, 1.08-2.4; P=0.02). CONCLUSIONS: The principal mechanism of acute cerebral infarction after aortic valve replacement is embolism. There are distinct factors associated with watershed and embolic infarct, some of which may be modifiable. PMID- 27382006 TI - Hemoglobin Concentration and Risk of Incident Stroke in Community-Living Adults. AB - BACKGROUND AND PURPOSE: In previous observational studies, hemoglobin concentrations have been associated with an increased risk of stroke. However, these studies were limited by a relatively low number of stroke events, making it difficult to determine whether the association of hemoglobin and stroke differed by demographic or clinical factors. METHODS: Using Cox proportional hazards analysis and Kaplan-Meier plots, we examined the association of baseline hemoglobin concentrations with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort of black and white adults aged >=45 years. RESULTS: A total of 518 participants developed stroke over a mean 7+/-2 years of follow-up. There was a statistically significant interaction between hemoglobin and sex (P=0.05) on the risk of incident stroke. In Cox regression models adjusted for demographic and clinical variables, there was no association of baseline hemoglobin concentration with incident stroke in men, whereas in women, the lowest (<12.4 g/dL) and highest (>14.0 g/dL) quartiles of hemoglobin were associated with higher risk of stroke when compared with the second quartile (12.4-13.2 g/dL; quartile 1: hazard ratio, 1.59; 95% confidence interval, 1.09-2.31; quartile 2: referent; quartile 3: hazard ratio, 0.91; 95% confidence interval, 0.59-1.38; quartile 4: hazard ratio, 1.59; 95% confidence interval, 1.08-2.35). Similar results were observed in models stratified by hemoglobin and sex and when hemoglobin was modeled as a continuous variable using restricted quadratic spline regression. CONCLUSIONS: Lower and higher hemoglobin concentrations were associated with a higher risk of incident stroke in women. No such associations were found in men. PMID- 27382007 TI - Response by Orito and Morioka to Letter Regarding Article, "Leakage Sign for Primary Intracerebral Hemorrhage: A Novel Predictor of Hematoma Growth". PMID- 27382008 TI - Letter by Murai Regarding Article, "Leakage Sign for Primary Intracerebral Hemorrhage: A Novel Predictor of Hematoma Growth". PMID- 27382009 TI - Prognosis of Ischemic Stroke With Newly Diagnosed Diabetes Mellitus According to Hemoglobin A1c Criteria in Chinese Population. AB - BACKGROUND AND PURPOSE: Hemoglobin A1c (HbA1c) was recommended to diagnose diabetes mellitus, but whether newly diagnosed diabetes mellitus (NDDM) according to the new criteria was associated with stroke prognosis was unclear. We aimed to investigate the prognosis of ischemic stroke with NDDM according to the new criteria. METHODS: Ischemic stroke without a diabetes mellitus history in the survey on Abnormal Glucose Regulation in Patients With Acute Stroke Across China were included in the analysis. NDDM was defined as fasting plasma glucose >=7.0 mmol/L, 2-hour oral glucose tolerance test >=11.1 mmol/L, or HbA1c >=6.5%, and NDDM was divided into group 1, diagnosed by glucose criteria (fasting plasma glucose >=7.0 mmol/L or 2-hour oral glucose tolerance test >=11.1 mmol/L with/without HbA1c >=6.5%), or group 2, diagnosed by single high HbA1c (fasting plasma glucose <7.0 mmol/L, 2-hour oral glucose tolerance test <11.1 mmol/L, and HbA1c >=6.5%). The association between NDDM and 1-year prognosis (mortality, stroke recurrence, and poor functional outcome [modified Rankin scale score 3-6]) was estimated. RESULTS: Among 1251 ischemic stroke patients, 539 were NDDM and 141 of NDDM with single high HbA1c. NDDM was an independent risk factor for 1 year mortality (hazard ratio, 1.12; 95% confidence interval, 1.001-1.26), stroke recurrence (hazard ratio, 1.14; 95% confidence interval, 1.01-1.28), and poor functional outcome (odds ratio, 2.58; 95% confidence interval, 1.95-3.43) compared with non-diabetes mellitus. Nevertheless, NDDM with single high HbA1c was not significantly associated with 1-year prognosis for all end points (P>0.05 for all). CONCLUSIONS: NDDM by new criteria was associated with poor prognosis at 1 year after ischemic stroke; however, NDDM with single high HbA1c did not predict a poor prognosis. PMID- 27382010 TI - Drifting towards ceftriaxone treatment failure in gonorrhoea: risk factor analysis of data from the Gonococcal Resistance to Antimicrobials Surveillance Programme in England and Wales. AB - OBJECTIVES: Treatment of Neisseria gonorrhoeae is threatened by the emergence of antimicrobial resistance. We analysed data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales to identify groups most at risk of reduced susceptibility to the currently recommended first line therapy, ceftriaxone. METHODS: Data from GRASP between 2007 and 2013 on ceftriaxone susceptibility and strain types were analysed. Risk factors associated with isolates exhibiting a ceftriaxone minimum inhibitory concentration (MIC) of >=0.015 mg/L (CTR >=0.015 mg/L) were identified using logistic regression. RESULTS: One third of isolates from men who have sex with men (MSM) (1279/4203) and 9.9% from heterosexuals (458/4626) exhibited CTR >=0.015 mg/L. Between 2007 and 2013, the modal MIC for isolates remained at 0.004 mg/L for MSM but increased from 0.002 to 0.004 mg/L for heterosexuals. Among MSM, CTR >=0.015 mg/L was associated with Asian ethnicity (crude OR: 1.42; 95% CI 1.07 to 1.88) and previous gonorrhoea (1.34; 1.16 to 1.54). Among heterosexuals, CTR >=0.015 mg/L was associated with older age (35+ years: 4.31; 3.34 to 5.55), >=6 sexual partners (1.58; 1.01 to 2.44) and sex abroad (2.23; 1.71 to 2.91). CTR >=0.015 mg/L was less likely in isolates from heterosexuals of black Caribbean or African ethnicity (0.29; 0.20 to 0.41, 0.66; 0.43 to 0.99), with a concurrent chlamydial infection (0.25; 0.19 to 0.34) or women (0.57; 0.46 to 0.71). Over 600 isolates (CTR >=0.015 mg/L) were typed; the majority were in Genogroup 1407, containing sequence type 1407. CONCLUSIONS: The emergence and spread of gonorrhoea with reduced susceptibility to ceftriaxone seems a realistic prospect, most likely in those involved in 'rapid-transmission' or bridging sexual networks. PMID- 27382013 TI - Characterization of a Novel M1 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator Radioligand, [3H]PT-1284. AB - Selective activation of the M1 muscarinic acetylcholine receptor (mAChR) via a positive allosteric modulator (PAM) is a new approach for the treatment of the cognitive impairments associated with schizophrenia and Alzheimer's disease. Herein, we describe the characterization of an M1 PAM radioligand, 8-((1S,2S)-2 hydroxycyclohexyl)-5-((6-(methyl-t3)pyridin-3-yl)methyl)-8,9-dihydro-7H pyrrolo[3,4-hour]quinolin-7-one ([(3)H]PT-1284), as a tool for characterizing the M1 allosteric binding site, as well as profiling novel M1 PAMs. 8-((1S,2S)-2 Hydroxycyclohexyl)-5-((6-methylpyridin-3-yl)methyl)-8,9-dihydro-7H-pyrrolo[3,4 hour]quinolin-7-one (PT-1284 ( 1: )) was shown to potentiate acetylcholine (ACh) in an M1 fluorometric imaging plate reader (FLIPR) functional assay (EC50, 36 nM) and carbachol in a hippocampal slice electrophysiology assay (EC50, 165 nM). PT 1284 ( 1: ) also reduced the concentration of ACh required to inhibit [(3)H]N methylscopolamine ([(3)H]NMS) binding to M1, left-shifting the ACh Ki approximately 19-fold at 10 MUM. Saturation analysis of a human M1 mAChR stable cell line showed that [(3)H]PT-1284 bound to M1 mAChR in the presence of 1 mM ACh with Kd, 4.23 nM, and saturable binding capacity (Bmax), 6.38 pmol/mg protein. M1 selective PAMs were shown to inhibit [(3)H]PT-1284 binding in a concentration responsive manner, whereas M1 allosteric and orthosteric agonists showed weak affinity (>30 MUM). A strong positive correlation (R(2) = 0.86) was found to exist between affinity values generated for nineteen M1 PAMs in the [(3)H]PT-1284 binding assay and the EC50 values of these ligands in a FLIPR functional potentiation assay. These data indicate that there is a strong positive correlation between M1 PAM binding affinity and functional activity, and that [(3)H]PT-1284 can serve as a tool for pharmacological investigation of M1 mAChR PAMs. PMID- 27382014 TI - The Follitropin Receptor: Matching Structure and Function. AB - Follitropin, or follicle-stimulating hormone (FSH) receptor (FSHR), is a G protein-coupled receptor belonging to the glycoprotein hormone receptor family that plays an essential role in reproduction. Although its primary location is the gonad, the FSHR has also been reported in extragonadal tissues including bone, placenta, endometrium, liver, and blood vessels from a number of malignant tumors. The recently resolved crystal structure of FSH bound to the entire FSHR ectodomain has been instrumental in more clearly defining the role of this domain in ligand binding and receptor activation. Biochemical, biophysical, and structural data also indicate that the FSHR exists as a higher order structure and that it may heterodimerize with its closely related receptor, the luteinizing hormone receptor; this association may have physiologic implications during ovarian follicle maturation given that both receptors may simultaneously coexist in the same cell. FSHR heterodimerization is unique to the ovary because in the testes, gonadotropin receptors are expressed in separate compartments. FSHR self association appears to be required for receptor coupling to multiple effectors and adaptors, for the activation of multiple signaling pathways and the transduction of asymmetric signaling, and for negative and positive receptor cooperativity. It also provides a mechanism through which the glycosylation variants of FSH may exert distinct and differential effects at the target cell level. Given its importance in regulating activation of distinct signaling pathways, functional selectivity at the FSHR is briefly discussed, as well as the potential implications of this particular functional feature on the design of new pharmacological therapies in reproduction. PMID- 27382012 TI - Hybrid Enzalutamide Derivatives with Histone Deacetylase Inhibitor Activity Decrease Heat Shock Protein 90 and Androgen Receptor Levels and Inhibit Viability in Enzalutamide-Resistant C4-2 Prostate Cancer Cells. AB - Histone deacetylase inhibitors (HDACIs) can disrupt the viability of prostate cancer (PCa) cells through modulation of the cytosolic androgen receptor (AR) chaperone protein heat shock protein 90 (HSP90). However, toxicities associated with their pleiotropic effects could contribute to the ineffectiveness of HDACIs in PCa treatment. We designed hybrid molecules containing partial chemical scaffolds of enzalutamide and suberoylanilide hydroxamic acid (SAHA), with weakened intrinsic pan-HDACI activities, to target HSP90 and AR in enzalutamide resistant PCa cells. The potency of the new molecules, compounds 2-75 [4-(3-(4 cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2 fluoro-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide] and 1005 [(E)-3-(4-(3-(4-cyano 3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2 fluorophenyl)-N-hydroxyacrylamide], as inhibitors of nuclear and cytosolic histone deacetylases was substantially lower than that of SAHA in cell-free and in situ assays. Compounds 2-75 and 1005 antagonized gene activation by androgen without inducing chromatin association of AR. Enzalutamide had no effect on the levels of AR or HSP90, whereas the hybrid compounds induced degradation of both AR and HSP90, similar to (compound 1005) or more potently than (compound 2-75) SAHA. Similar to SAHA, compounds 2-75 and 1005 decreased the level of HSP90 and induced acetylation in a predicted approximately 55 kDa HSP90 fragment. Compared with SAHA, compound 2-75 induced greater hyperacetylation of the HDAC6 substrate alpha-tubulin. In contrast with SAHA, neither hybrid molecule caused substantial hyperacetylation of histones H3 and H4. Compounds 2-75 and 1005 induced p21 and caused loss of viability in the enzalutamide-resistant C4-2 cells, with efficacies that were comparable to or better than SAHA. The results suggest the potential of the new compounds as prototype antitumor drugs that would downregulate HSP90 and AR in enzalutamide-resistant PCa cells with weakened effects on nuclear HDACI targets. PMID- 27382015 TI - Trigeminocardiac reflex caused by selective angiography of the middle meningeal artery. AB - We describe an interesting case of trigeminocardiac reflex (TCR) caused by selective angiography of the middle meningeal artery (MMA). A 28-year-old woman presented with a symptomatic meningioma. Preoperative tumour embolisation was performed. In the procedure, when selective MMA angiography was done with Omnipaque 300 mg I/mL for 3 mL by manual injection, the patient complained of flashing lights in her eye followed by vomiting and bradycardia down to 40 bpm without increased intracranial pressure signs. On selective MMA angiography, the choroidal crescent and arteries of the periorbital region were opacified by anastomosis from the MMA via the meningo-ophthalmic artery. We diagnosed that her symptoms were caused by selective MMA angiography leading to high pressure stimulation towards the ophthalmic nerve innervation around the orbit as a TCR. We suggest that the operator should be prepared to manage TCR during treatment with expected selective MMA angiography, and gentle low pressure contrast injection should be attempted. PMID- 27382016 TI - Burning mouth syndrome associated with varicella zoster virus. AB - We present two cases of burning mouth syndrome (BMS)-of 8-month duration in a 61 year-old woman and of 2-year duration in a 63-year-old woman-both associated with increased levels of antivaricella zoster virus (VZV) IgM antibodies in serum and with pain that improved with antiviral treatment. Combined with our previous finding of BMS due to herpes simplex virus type 1 (HSV-1) infection, we recommend evaluation of patients with BMS not only for VZV or HSV-1 DNA in the saliva, but also for serum anti-VZV and anti-HSV-1 IgM antibodies. Both infections are treatable with oral antiviral agents. PMID- 27382017 TI - Unusual foreign body in primary tooth. PMID- 27382018 TI - The Chlamydia-Secreted Protease CPAF Promotes Chlamydial Survival in the Mouse Lower Genital Tract. AB - Despite the extensive in vitro characterization of CPAF (chlamydial protease/proteasome-like activity factor), its role in chlamydial infection and pathogenesis remains unclear. We now report that a Chlamydia trachomatis strain deficient in expression of CPAF (L2-17) is no longer able to establish a successful infection in the mouse lower genital tract following an intravaginal inoculation. The L2-17 organisms were cleared from the mouse lower genital tract within a few days, while a CPAF-sufficient C. trachomatis strain (L2-5) survived in the lower genital tract for more than 3 weeks. However, both the L2-17 and L2 5 organisms maintained robust infection courses that lasted up to 4 weeks when they were directly delivered into the mouse upper genital tract. The CPAF dependent chlamydial survival in the lower genital tract was confirmed in multiple strains of mice. Thus, we have demonstrated a critical role of CPAF in promoting C. trachomatis survival in the mouse lower genital tracts. It will be interesting to further investigate the mechanisms of the CPAF-dependent chlamydial pathogenicity. PMID- 27382019 TI - Infectivity of Plasmodium falciparum in Malaria-Naive Individuals Is Related to Knob Expression and Cytoadherence of the Parasite. AB - Plasmodium falciparum is the most virulent human malaria parasite because of its ability to cytoadhere in the microvasculature. Nonhuman primate studies demonstrated relationships among knob expression, cytoadherence, and infectivity. This has not been examined in humans. Cultured clinical-grade P. falciparum parasites (NF54, 7G8, and 3D7B) and ex vivo-derived cell banks were characterized. Knob and knob-associated histidine-rich protein expression, CD36 adhesion, and antibody recognition of parasitized erythrocytes (PEs) were evaluated. Parasites from the cell banks were administered to malaria-naive human volunteers to explore infectivity. For the NF54 and 3D7B cell banks, blood was collected from the study participants for in vitro characterization. All parasites were infective in vivo However, infectivity of NF54 was dramatically reduced. In vitro characterization revealed that unlike other cell bank parasites, NF54 PEs lacked knobs and did not cytoadhere. Recognition of NF54 PEs by immune sera was observed, suggesting P. falciparum erythrocyte membrane protein 1 expression. Subsequent recovery of knob expression and CD36-mediated adhesion were observed in PEs derived from participants infected with NF54. Knobless cell bank parasites have a dramatic reduction in infectivity and the ability to adhere to CD36. Subsequent infection of malaria-naive volunteers restored knob expression and CD36-mediated cytoadherence, thereby showing that the human environment can modulate virulence. PMID- 27382020 TI - A Nonoligomerizing Mutant Form of Helicobacter pylori VacA Allows Structural Analysis of the p33 Domain. AB - Helicobacter pylori secretes a pore-forming VacA toxin that has structural features and activities substantially different from those of other known bacterial toxins. VacA can assemble into multiple types of water-soluble flower shaped oligomeric structures, and most VacA activities are dependent on its capacity to oligomerize. The 88-kDa secreted VacA protein can undergo limited proteolysis to yield two domains, designated p33 and p55. The p33 domain is required for membrane channel formation and intracellular toxic activities, and the p55 domain has an important role in mediating VacA binding to cells. Previous studies showed that the p55 domain has a predominantly beta-helical structure, but no structural data are available for the p33 domain. We report here the purification and analysis of a nonoligomerizing mutant form of VacA secreted by H. pylori The nonoligomerizing 88-kDa mutant protein retains the capacity to enter host cells but lacks detectable toxic activity. Analysis of crystals formed by the monomeric protein reveals that the beta-helical structure of the p55 domain extends into the C-terminal portion of p33. Fitting the p88 structural model into an electron microscopy map of hexamers formed by wild-type VacA (predicted to be structurally similar to VacA membrane channels) reveals that p55 and the beta-helical segment of p33 localize to peripheral arms but do not occupy the central region of the hexamers. We propose that the amino-terminal portion of p33 is unstructured when VacA is in a monomeric form and that it undergoes a conformational change during oligomer assembly. PMID- 27382021 TI - Affinity-Based Screening of Tetravalent Peptides Identifies Subtype-Selective Neutralizers of Shiga Toxin 2d, a Highly Virulent Subtype, by Targeting a Unique Amino Acid Involved in Its Receptor Recognition. AB - Shiga toxin (Stx), a major virulence factor of enterohemorrhagic Escherichia coli (EHEC), can be classified into two subgroups, Stx1 and Stx2, each consisting of various closely related subtypes. Stx2 subtypes Stx2a and Stx2d are highly virulent and linked with serious human disorders, such as acute encephalopathy and hemolytic-uremic syndrome. Through affinity-based screening of a tetravalent peptide library, we previously developed peptide neutralizers of Stx2a in which the structure was optimized to bind to the B-subunit pentamer. In this study, we identified Stx2d-selective neutralizers by targeting Asn16 of the B subunit, an amino acid unique to Stx2d that plays an essential role in receptor binding. We synthesized a series of tetravalent peptides on a cellulose membrane in which the core structure was exactly the same as that of peptides in the tetravalent library. A total of nine candidate motifs were selected to synthesize tetravalent forms of the peptides by screening two series of the tetravalent peptides. Five of the tetravalent peptides effectively inhibited the cytotoxicity of Stx2a and Stx2d, and notably, two of the peptides selectively inhibited Stx2d. These two tetravalent peptides bound to the Stx2d B subunit with high affinity dependent on Asn16. The mechanism of binding to the Stx2d B subunit differed from that of binding to Stx2a in that the peptides covered a relatively wide region of the receptor-binding surface. Thus, this highly optimized screening technique enables the development of subtype-selective neutralizers, which may lead to more sophisticated treatments of infections by Stx-producing EHEC. PMID- 27382022 TI - Beneficial Effects of Sodium Phenylbutyrate Administration during Infection with Salmonella enterica Serovar Typhimurium. AB - Sodium phenylbutyrate (PBA) is a derivative of the short-chain fatty acid butyrate and is approved for treatment of urea cycle disorders and progressive familial intrahepatic cholestasis type 2. Previously known functions include histone deacetylase inhibitor, endoplasmic reticulum stress inhibitor, ammonia sink, and chemical chaperone. Here, we show that PBA has a previously undiscovered protective role in host mucosal defense during infection. Administration of PBA to Taconic mice resulted in the increase of intestinal Lactobacillales and segmented filamentous bacteria (SFB), as well as an increase of interleukin 17 (IL-17) production by intestinal cells. This effect was not observed in Jackson Laboratory mice, which are not colonized with SFB. Because previous studies showed that IL-17 plays a protective role during infection with mucosal pathogens, we hypothesized that Taconic mice treated with PBA would be more resistant to infection with Salmonella enterica serovar Typhimurium (S Typhimurium). By using the streptomycin-treated mouse model, we found that Taconic mice treated with PBA exhibited significantly lower S Typhimurium intestinal colonization and dissemination to the reticuloendothelial system, as well as lower levels of inflammation. The lower levels of S Typhimurium gut colonization and intestinal inflammation were not observed in Jackson Laboratory mice. Although PBA had no direct effect on bacterial replication, its administration reduced S Typhimurium epithelial cell invasion and lowered the induction of the proinflammatory cytokine IL-23 in macrophage-like cells. These effects likely contributed to the better outcome of infection in PBA-treated mice. Overall, our results suggest that PBA induces changes in the microbiota and in the mucosal immune response that can be beneficial to the host during infection with S Typhimurium and possibly other enteric pathogens. PMID- 27382023 TI - Burkholderia pseudomallei Rapidly Infects the Brain Stem and Spinal Cord via the Trigeminal Nerve after Intranasal Inoculation. AB - Infection with Burkholderia pseudomallei causes melioidosis, a disease with a high mortality rate (20% in Australia and 40% in Southeast Asia). Neurological melioidosis is particularly prevalent in northern Australian patients and involves brain stem infection, which can progress to the spinal cord; however, the route by which the bacteria invade the central nervous system (CNS) is unknown. We have previously demonstrated that B. pseudomallei can infect the olfactory and trigeminal nerves within the nasal cavity following intranasal inoculation. As the trigeminal nerve projects into the brain stem, we investigated whether the bacteria could continue along this nerve to penetrate the CNS. After intranasal inoculation of mice, B. pseudomallei caused low-level localized infection within the nasal cavity epithelium, prior to invasion of the trigeminal nerve in small numbers. B. pseudomallei rapidly invaded the trigeminal nerve and crossed the astrocytic barrier to enter the brain stem within 24 h and then rapidly progressed over 2,000 MUm into the spinal cord. To rule out that the bacteria used a hematogenous route, we used a capsule-deficient mutant of B. pseudomallei that does not survive in the blood and found that it also entered the CNS via the trigeminal nerve. This suggests that the primary route of entry is via the nerves that innervate the nasal cavity. We found that actin-mediated motility could facilitate initial infection of the olfactory epithelium. Thus, we have demonstrated that B. pseudomallei can rapidly infect the brain and spinal cord via the trigeminal nerve branches that innervate the nasal cavity. PMID- 27382024 TI - CagA Phosphorylation in Helicobacter pylori-Infected B Cells Is Mediated by the Nonreceptor Tyrosine Kinases of the Src and Abl Families. AB - CagA is one of the most important virulence factors of the human pathogen Helicobacter pylori CagA expression can be associated with the induction of severe gastric disorders such as gastritis, ulceration, gastric cancer, or mucosa associated lymphoid tissue (MALT) lymphoma. After translocation through a type IV secretion system into epithelial cells, CagA is tyrosine phosphorylated by kinases of the Src and Abl families, leading to drastic cell elongation and motility. While the functional role of CagA in epithelial cells is well investigated, knowledge about CagA phosphorylation and its associated signal transduction pathways in B cells is only marginal. Here, we established the B cell line MEC1 derived from a B cell chronic lymphocytic leukemia (B-CLL) patient as a new infection model to study the signal transduction in B cells controlled by H. pylori We observed that CagA was rapidly injected, strongly tyrosine phosphorylated, and cleaved into a 100-kDa N-terminal and a 40-kDa C-terminal fragment. To identify upstream signal transduction pathways of CagA phosphorylation in MEC1 cells, pharmacological inhibitors were employed to specifically target Src and Abl kinases. We observed that CagA phosphorylation was strongly inhibited upon treatment with an Src inhibitor and slightly diminished when the Abl kinase inhibitor imatinib mesylate (Gleevec) was applied. The addition of dasatinib to block c-Abl and Src kinases led to a complete loss of CagA phosphorylation. In conclusion, these results demonstrate an important role for Src and Abl tyrosine kinases in CagA phosphorylation in B cells, which represent druggable targets in H. pylori-mediated gastric MALT lymphoma. PMID- 27382026 TI - Ca2+ controls gating of voltage-gated calcium channels by releasing the beta2e subunit from the plasma membrane. AB - Voltage-gated calcium (Cav) channels, which are regulated by membrane potential, cytosolic Ca(2+), phosphorylation, and membrane phospholipids, govern Ca(2+) entry into excitable cells. Cav channels contain a pore-forming alpha1 subunit, an auxiliary alpha2delta subunit, and a regulatory beta subunit, each encoded by several genes in mammals. In addition to a domain that interacts with the alpha1 subunit, beta2e and beta2a also interact with the cytoplasmic face of the plasma membrane through an electrostatic interaction for beta2e and posttranslational acylation for beta2a. We found that an increase in cytosolic Ca(2+) promoted the release of beta2e from the membrane without requiring substantial depletion of the anionic phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) from the plasma membrane. Experiments with liposomes indicated that Ca(2+) disrupted the interaction of the beta2e amino-terminal peptide with membranes containing PIP2 Ca(2+) binding to calmodulin (CaM) leads to CaM-mediated inactivation of Cav currents. Although Cav2.2 coexpressed with beta2a required Ca(2+)-dependent activation of CaM for Ca(2+)-mediated reduction in channel activity, Cav2.2 coexpressed with beta2e exhibited Ca(2+)-dependent inactivation of the channel even in the presence of Ca(2+)-insensitive CaM. Inducible depletion of PIP2 reduced Cav2.2 currents, and in cells coexpressing beta2e, but not a form that lacks the polybasic region, increased intracellular Ca(2+) further reduced Cav2.2 currents. Many hormone- or neurotransmitter-activated receptors stimulate PIP2 hydrolysis and increase cytosolic Ca(2+); thus, our findings suggest that beta2e may integrate such receptor-mediated signals to limit Cav activity. PMID- 27382025 TI - A comprehensive analysis of 3' end sequencing data sets reveals novel polyadenylation signals and the repressive role of heterogeneous ribonucleoprotein C on cleavage and polyadenylation. AB - Alternative polyadenylation (APA) is a general mechanism of transcript diversification in mammals, which has been recently linked to proliferative states and cancer. Different 3' untranslated region (3' UTR) isoforms interact with different RNA-binding proteins (RBPs), which modify the stability, translation, and subcellular localization of the corresponding transcripts. Although the heterogeneity of pre-mRNA 3' end processing has been established with high-throughput approaches, the mechanisms that underlie systematic changes in 3' UTR lengths remain to be characterized. Through a uniform analysis of a large number of 3' end sequencing data sets, we have uncovered 18 signals, six of which are novel, whose positioning with respect to pre-mRNA cleavage sites indicates a role in pre-mRNA 3' end processing in both mouse and human. With 3' end sequencing we have demonstrated that the heterogeneous ribonucleoprotein C (HNRNPC), which binds the poly(U) motif whose frequency also peaks in the vicinity of polyadenylation (poly(A)) sites, has a genome-wide effect on poly(A) site usage. HNRNPC-regulated 3' UTRs are enriched in ELAV-like RBP 1 (ELAVL1) binding sites and include those of the CD47 gene, which participate in the recently discovered mechanism of 3' UTR-dependent protein localization (UDPL). Our study thus establishes an up-to-date, high-confidence catalog of 3' end processing sites and poly(A) signals, and it uncovers an important role of HNRNPC in regulating 3' end processing. It further suggests that U-rich elements mediate interactions with multiple RBPs that regulate different stages in a transcript's life cycle. PMID- 27382027 TI - An RYR1 mutation associated with malignant hyperthermia is also associated with bleeding abnormalities. AB - Malignant hyperthermia is a potentially fatal hypermetabolic disorder triggered by halogenated anesthetics and the myorelaxant succinylcholine in genetically predisposed individuals. About 50% of susceptible individuals carry dominant, gain-of-function mutations in RYR1 [which encodes ryanodine receptor type 1 (RyR1)], though they have normal muscle function and no overt clinical symptoms. RyR1 is predominantly found in skeletal muscle but also at lower amounts in immune and smooth muscle cells, suggesting that RYR1 mutations may have a wider range of effects than previously suspected. Mild bleeding abnormalities have been described in patients with malignant hyperthermia carrying gain-of-function RYR1 mutations. We sought to determine the frequency and molecular basis for this symptom. We found that some patients with specific RYR1 mutations had abnormally high bleeding scores, whereas their healthy relatives did not. Knock-in mice with the malignant hyperthermia susceptibility RYR1 mutation Y522S (MHS RYR1Y522S) had longer bleeding times than their wild-type littermates. Primary vascular smooth muscle cells from RYR1Y522S knock-in mice exhibited a higher frequency of subplasmalemmal Ca(2+) sparks, leading to a more negative resting membrane potential. The bleeding defect of RYR1Y522S mice and of one patient was reversed by treatment with the RYR1 antagonist dantrolene, and Ca(2+) sparks in primary vascular smooth muscle cells from the MHS RYR1Y522S mice were blocked by ryanodine or dantrolene. Thus, RYR1 mutations may lead to prolonged bleeding by altering vascular smooth muscle cell function. The reversibility of the bleeding phenotype emphasizes the potential therapeutic value of dantrolene in the treatment of such bleeding disorders. PMID- 27382028 TI - Mapping the subcellular mechanical properties of live cells in tissues with fluorescence emission-Brillouin imaging. AB - Extracellular matrices (ECMs) are central to the advent of multicellular life, and their mechanical properties are modulated by and impinge on intracellular signaling pathways that regulate vital cellular functions. High spatial resolution mapping of mechanical properties in live cells is, however, extremely challenging. Thus, our understanding of how signaling pathways process physiological signals to generate appropriate mechanical responses is limited. We introduce fluorescence emission-Brillouin scattering imaging (FBi), a method for the parallel and all-optical measurements of mechanical properties and fluorescence at the submicrometer scale in living organisms. Using FBi, we showed that changes in cellular hydrostatic pressure and cytoplasm viscoelasticity modulate the mechanical signatures of plant ECMs. We further established that the measured "stiffness" of plant ECMs is symmetrically patterned in hypocotyl cells undergoing directional growth. Finally, application of this method to Arabidopsis thaliana with photoreceptor mutants revealed that red and far-red light signals are essential modulators of ECM viscoelasticity. By mapping the viscoelastic signatures of a complex ECM, we provide proof of principle for the organism-wide applicability of FBi for measuring the mechanical outputs of intracellular signaling pathways. As such, our work has implications for investigations of mechanosignaling pathways and developmental biology. PMID- 27382029 TI - Lenalidomide in Relapsed or Refractory Diffuse Large B-Cell Lymphoma: Is It a Valid Treatment Option? AB - BACKGROUND: Despite the advent of new treatment strategies, many patients with diffuse large B-cell lymphoma (DLBCL) relapse or die of the disease. Prospective clinical trials have demonstrated that lenalidomide is an effective and safe treatment option, especially for non-germinal center B-cell (non-GCB) DLBCL. However, routine clinical data are lacking, which is why we provide the results of the so-far largest relapsed/refractory (R/R) DLBCL real-life analysis. METHODS: We retrospectively assessed 123 R/R DLBCL patients who received either 15 or 25 mg/day of lenalidomide from January 2006 to January 2015. RESULTS: During a median follow-up period of 4.5 years, complete remission was achieved in 32% and a partial remission in 33% non-GCB patients compared with 0% and 3% in the GCB group (p < .001 and .001, respectively), with median response durations of 15 and 5 months, respectively (p < .001). Lenalidomide at 25 mg was superior to 15 mg in terms of response (complete remission 21% and partial remission 23% vs. 0% and 8%; p = .007 and .05) and median response duration (10 vs. 4 months; p = .03). Toxicity was limited and reversible. Median progression-free survival differed between non-GCB and GCB patients (37 vs. 30 months; p < .001) and between the two dosages (24 vs. 34 months; p = .002). However, overall survival was similar between the subgroups (38-42 months). CONCLUSION: We provide evidence that lenalidomide is a valid treatment option for R/R DLBCL, with limited and reversible toxicity, and is more efficient in non-GCB DLBCL and at higher doses. IMPLICATIONS FOR PRACTICE: Despite the advent of new treatment strategies, many patients with diffuse large B-cell lymphoma (DLBCL) relapse or die of the disease; hence, novel therapeutic approaches are urgently needed. This study confirms that lenalidomide is a valid and well-tolerated treatment option for relapsed/refractory (R/R) DLBCL. Superior outcomes were observed in non-germinal center B-cell (GCB) DLBCL, probably because of inhibition of the nuclear factor kappaB pathway. Similarly, high drug doses resulted in greater clinical benefits. Overall, lenalidomide is a suitable therapeutic option for R/R DLBCL, especially in non-GCB DLBCL, and 25 mg/day dosing should be preferred. PMID- 27382030 TI - Outcome of Patients With Metastatic Chromophobe Renal Cell Carcinoma Treated With Sunitinib. AB - BACKGROUND: Sunitinib is a standard treatment for metastatic clear cell renal cell carcinoma (mccRCC). Data on its activity in the rare variant of metastatic chromophobe renal cell carcinoma (mchRCC), are limited. We aimed to analyze the activity of sunitinib in a relatively large and homogenous international cohort of mchRCC patients in terms of outcome and comparison with mccRCC. METHODS: Records from mchRCC patients treated with first-line sunitinib in 10 centers across 4 countries were retrospectively reviewed. Univariate and multivariate analyses of association between clinicopathologic factors and outcome were performed. Subsequently, mchRCC patients were individually matched to mccRCC patients. We compared the clinical benefit rate, progression-free survival (PFS), and overall survival (OS) between the groups. RESULTS: Between 2004 and 2014, 36 patients (median age, 64 years; 47% male) with mchRCC were treated with first line sunitinib. Seventy-eight percent achieved a clinical benefit (partial response + stable disease). Median PFS and OS were 10 and 26 months, respectively. Factors associated with PFS were the Heng risk (hazard ratio [HR], 3.3; p = .03) and pretreatment neutrophil-to-lymphocyte ratio (NLR) >3 (HR, 0.63; p = .02). Factors associated with OS were the Heng risk (HR, 4.1; p = .04), liver metastases (HR, 3.8; p = .03), and pretreatment NLR <3 (HR, 0.55; p = .03). Treatment outcome was not significantly different between mchRCC patients and individually matched mccRCC patients. In mccRCC patients (p value versus mchRCC), 72% achieved a clinical benefit (p = .4) and median PFS and OS were 9 (p = .6) and 25 (p = .7) months, respectively. CONCLUSION: In metastatic chromophobe renal cell carcinoma, sunitinib therapy may be associated with similar outcome and toxicities as in metastatic clear cell renal cell carcinoma. The Heng risk and pretreatment NLR may be associated with PFS and OS. IMPLICATIONS FOR PRACTICE: Data on the activity of sunitinib in metastatic chromophobe renal cell carcinoma (mchRCC) are limited. This study analyzed the activity of sunitinib in a cohort of mchRCC patients. Of 36 patients with mchRCC who were treated with first-line sunitinib, 78% achieved a clinical benefit. Median PFS and OS were 10 and 26 months, respectively. Treatment outcome was not significantly different between mchRCC patients and individually matched metastatic clear cell RCC patients. PMID- 27382032 TI - Excision of recurrent bilateral elastofibroma dorsi: A rare image. PMID- 27382031 TI - Location of Primary Tumor and Benefit From Anti-Epidermal Growth Factor Receptor Monoclonal Antibodies in Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer. AB - INTRODUCTION: Right- and left-sided colorectal cancers (CRCs) differ in clinical and molecular characteristics. Some retrospective analyses suggested that patients with right-sided tumors derive less benefit from anti-epidermal growth factor receptor (EGFR) antibodies; however, molecular selection in those studies was not extensive. PATIENTS AND METHODS: Patients with RAS and BRAF wild-type metastatic CRC (mCRC) who were treated with single-agent anti-EGFRs or with cetuximab-irinotecan (if refractory to previous irinotecan) were included in the study. Differences in outcome between patients with right- and left-sided tumors were investigated. RESULTS: Of 75 patients, 14 and 61 had right- and left-sided tumors, respectively. None of the right-sided tumors responded according to RECIST, compared with 24 left-sided tumors (overall response rate: 0% vs. 41%; p = .0032), and only 2 patients with right-sided tumors (15%) versus 47 patients with left-sided tumors (80%) achieved disease control (p < .0001). The median duration of progression-free survival was 2.3 and 6.6 months in patients with right-sided and left-sided tumors, respectively (hazard ratio: 3.97; 95% confidence interval: 2.09-7.53; p < .0001). CONCLUSION: Patients with right-sided RAS and BRAF wild-type mCRC seemed to derive no benefit from single-agent anti EGFRs. IMPLICATIONS FOR PRACTICE: Right- and left-sided colorectal tumors have peculiar epidemiological and clinicopathological characteristics, distinct gene expression profiles and genetic alterations, and different prognoses. This study assessed the potential predictive impact of primary tumor site with regard to anti-epidermal growth factor receptor (EGFR) monoclonal antibody treatment in patients with RAS and BRAF wild-type metastatic colorectal cancer. The results demonstrated the lack of activity of anti-EGFRs in RAS and BRAF wild-type, right sided tumors, thus suggesting a potential role for primary tumor location in driving treatment choices. PMID- 27382033 TI - Low resting metabolic rate in exercise-associated amenorrhea is not due to a reduced proportion of highly active metabolic tissue compartments. AB - Exercising women with menstrual disturbances frequently display a low resting metabolic rate (RMR) when RMR is expressed relative to body size or lean mass. However, normalizing RMR for body size or lean mass does not account for potential differences in the size of tissue compartments with varying metabolic activities. To explore whether the apparent RMR suppression in women with exercise-associated amenorrhea is a consequence of a lower proportion of highly active metabolic tissue compartments or the result of metabolic adaptations related to energy conservation at the tissue level, RMR and metabolic tissue compartments were compared among exercising women with amenorrhea (AMEN; n = 42) and exercising women with eumenorrheic, ovulatory menstrual cycles (OV; n = 37). RMR was measured using indirect calorimetry and predicted from the size of metabolic tissue compartments as measured by dual-energy X-ray absorptiometry (DEXA). Measured RMR was lower than DEXA-predicted RMR in AMEN (1,215 +/- 31 vs. 1,327 +/- 18 kcal/day, P < 0.001) but not in OV (1,284 +/- 24 vs. 1,252 +/- 17, P = 0.16), resulting in a lower ratio of measured to DEXA-predicted RMR in AMEN (91 +/- 2%) vs. OV (103 +/- 2%, P < 0.001). AMEN displayed proportionally more residual mass (P < 0.001) and less adipose tissue (P = 0.003) compared with OV. A lower ratio of measured to DXA-predicted RMR was associated with lower serum total triiodothyronine (rho = 0.38, P < 0.001) and leptin (rho = 0.32, P = 0.004). Our findings suggest that RMR suppression in this population is not the result of a reduced size of highly active metabolic tissue compartments but is due to metabolic and endocrine adaptations at the tissue level that are indicative of energy conservation. PMID- 27382034 TI - Short-term and long-term effects of submaximal maternal exercise on offspring glucose homeostasis and pancreatic function. AB - Only a few studies have explored the effects of maternal exercise during gestation on adult offspring metabolism. We set out to test whether maternal controlled submaximal exercise maintained troughout all gestational periods induces persistant metabolic changes in the offspring. We used a model of 15-wk old nulliparous female Wistar rats that exercised (trained group) before and during gestation at a submaximal intensity or remained sedentary (control group). At weaning, male offspring from trained dams showed reduced basal glycemia (119.7 +/- 2.4 vs. 130.5 +/- 4.1 mg/dl, P < 0.05), pancreas relative weight (3.96 +/- 0.18 vs. 4.54 +/- 0.14 g/kg body wt, P < 0.05), and islet mean area (22,822 +/- 4,036 vs. 44,669 +/- 6,761 MUm(2), P < 0.05) compared with pups from control dams. Additionally, they had better insulin secretory capacity when stimulated by 2.8 mM glucose + 20 mM arginine compared with offspring from control dams (+96%, P < 0.05). At 7 mo of age, offspring from trained mothers displayed altered glucose tolerance (AUC = 15,285 +/- 527 vs. 11,898 +/- 988 mg.dl(-1).120 min, P < 0.05) and decreased muscle insulin sensitivity estimated by the phosphorylated PKB/total PKB ratio (-32%, P < 0.05) and tended to have a reduced islet insulin secretory capacity compared with rats from control dams. These results suggest that submaximal maternal exercise modifies short-term male offspring pancreatic function and appears to have rather negative long-term consequences on sedentary adult offspring glucose handling. PMID- 27382035 TI - Targeting ceramide metabolism in obesity. AB - Obesity is a major health concern that increases the risk for insulin resistance, type 2 diabetes (T2D), and cardiovascular disease. Thus, an enormous research effort has been invested into understanding how obesity-associated dyslipidemia and obesity-induced alterations in lipid metabolism increase the risk for these diseases. Accordingly, it has been proposed that the accumulation of lipid metabolites in organs such as the liver, skeletal muscle, and heart is critical to these obesity-induced pathologies. Ceramide is one such lipid metabolite that accumulates in tissues in response to obesity, and both pharmacological and genetic strategies that reduce tissue ceramide levels yield salutary actions on overall metabolic health. We will review herein why ceramide accumulates in tissues during obesity and how an increase in intracellular ceramide impacts cellular signaling and function as well as potential mechanisms by which reducing intracellular ceramide levels improves insulin resistance, T2D, atherosclerosis, and heart failure. Because a reduction in skeletal muscle ceramide levels is frequently associated with improvements in insulin sensitivity in humans, the beneficial findings reported for reducing ceramides in preclinical studies may have clinical application in humans. Therefore, modulating ceramide metabolism may be a novel, exciting target for preventing and/or treating obesity-related diseases. PMID- 27382036 TI - Control of skeletal muscle atrophy in response to disuse: clinical/preclinical contentions and fallacies of evidence. AB - Muscle wasting resulting wholly or in part from disuse represents a serious medical complication that, when prolonged, can increase morbidity and mortality. Although much knowledge has been gained over the past half century, the underlying etiology by which disuse alters muscle proteostasis remains enigmatic. Multidisciplinary and novel methodologies are needed to fill gaps and overcome barriers to improved patient care. The present review highlights seminal concepts from a symposium at Experimental Biology 2016. These proceedings focus on 1) the role of insulin resistance in mediating disuse-induced changes in muscle protein synthesis (MPS) and breakdown (MPB), as well as cross-talk between carbohydrate and protein metabolism; 2) the relative importance of MPS/MPB in mediating involuntary muscle loss in humans and animals; 3) interpretative limitations associated with MPS/MPB "markers," e.g., MuRF1/MAFbx mRNA; and finally, 4) how OMIC technologies can be leveraged to identify molecular pathways (e.g., ATF4, p53, p21) mediating disuse atrophy. This perspective deals primarily with "simple atrophy" due to unloading. Nonetheless, it is likely that disuse is a pervasive contributor to muscle wasting associated with catabolic disease-related atrophy (i.e., due to associated sedentary behaviour of disease burden). Key knowledge gaps and challenges are identified to stimulate discussion and identify opportunities for translational research. Data from animal and human studies highlight both similarities and differences. Integrated preclinical and clinical research is encouraged to better understand the metabolic and molecular underpinnings and translational relevance,for disuse atrophy. These approaches are crucial to clinically prevent or reverse muscle atrophy, thereby reestablishing homeostasis and recovery. PMID- 27382037 TI - Hypermetabolism and hypercatabolism of skeletal muscle accompany mitochondrial stress following severe burn trauma. AB - Burn trauma results in prolonged hypermetabolism and skeletal muscle wasting. How hypermetabolism contributes to muscle wasting in burn patients remains unknown. We hypothesized that oxidative stress, cytosolic protein degradation, and mitochondrial stress as a result of hypermetabolism contribute to muscle cachexia postburn. Patients (n = 14) with burns covering >30% of their total body surface area were studied. Controls (n = 13) were young healthy adults. We found that burn patients were profoundly hypermetabolic at both the skeletal muscle and systemic levels, indicating increased oxygen consumption by mitochondria. In skeletal muscle of burn patients, concurrent activation of mTORC1 signaling and elevation in the fractional synthetic rate paralleled increased levels of proteasomes and elevated fractional breakdown rate. Burn patients had greater levels of oxidative stress markers as well as higher expression of mtUPR-related genes and proteins, suggesting that burns increased mitochondrial stress and protein damage. Indeed, upregulation of cytoprotective genes suggests hypermetabolism-induced oxidative stress postburn. In parallel to mtUPR activation postburn, mitochondrial-specific proteases (LONP1 and CLPP) and mitochondrial translocases (TIM23, TIM17B, and TOM40) were upregulated, suggesting increased mitochondrial protein degradation and transport of preprotein, respectively. Our data demonstrate that proteolysis occurs in both the cytosolic and mitochondrial compartments of skeletal muscle in severely burned patients. Increased mitochondrial protein turnover may be associated with increased protein damage due to hypermetabolism-induced oxidative stress and activation of mtUPR. Our results suggest a novel role for the mitochondria in burn-induced cachexia. PMID- 27382038 TI - Age-related Differences in Dystrophin: Impact on Force Transfer Proteins, Membrane Integrity, and Neuromuscular Junction Stability. AB - The loss of muscle strength with age has been studied from the perspective of a decline in muscle mass and neuromuscular junction (NMJ) stability. A third potential factor is force transmission. The purpose of this study was to determine the changes in the force transfer apparatus within aging muscle and the impact on membrane integrity and NMJ stability. We measured an age-related loss of dystrophin protein that was greatest in the flexor muscles. The loss of dystrophin protein occurred despite a twofold increase in dystrophin mRNA. Importantly, this disparity could be explained by the four- to fivefold upregulation of the dystromir miR-31. To compensate for the loss of dystrophin protein, aged muscle contained increased alpha-sarcoglycan, syntrophin, sarcospan, laminin, beta1-integrin, desmuslin, and the Z-line proteins alpha actinin and desmin. In spite of the adaptive increase in other force transfer proteins, over the 48 hours following lengthening contractions, the old muscles showed more signs of impaired membrane integrity (fourfold increase in immunoglobulin G-positive fibers and 70% greater dysferlin mRNA) and NMJ instability (14- to 96-fold increases in Runx1, AchRdelta, and myogenin mRNA). Overall, these data suggest that age-dependent alterations in dystrophin leave the muscle membrane and NMJ more susceptible to contraction-induced damage even before changes in muscle mass are obvious. PMID- 27382039 TI - Relationship of Objectively-Measured Habitual Physical Activity to Chronic Inflammation and Fatigue in Middle-Aged and Older Adults. AB - BACKGROUND: Habitual (non-exercise) physical activity (PA) declines with age, and aging-related increases in inflammation and fatigue may be important contributors to variability in PA. METHODS: This study examined the association of objectively measured PA (accelerometry over 7 days) with inflammation (plasma interleukin-6 and C-reactive protein) and with self-reported fatigue (SF-36 Vitality) at baseline and 18 months after a diet-induced weight loss, exercise, or diet induced weight loss plus exercise intervention in 167 overweight/obese, middle aged, and older adults. RESULTS: At baseline, individuals with higher plasma interleukin-6, as well as those who reported feeling less energetic (more fatigued), took less steps per day and had lower PA energy expenditure and minutes of light and moderate-vigorous PA (p < .05 for all). At the 18-month follow-up, inflammation was lower in both weight loss groups, fatigue was reduced in all three groups with larger decreases in the combined group, and mean levels of habitual PA were not changed in any group. In longitudinal analyses with all groups combined, we found that participants reporting larger increases in vitality (eg, declines in fatigue) had greater increases in PA (p < .05 for all). Also, changes in steps/d and physical activity energy expenditure were indirectly associated with changes in interleukin-6 (beta [SEM] for steps/d = -565 [253]; beta [SEM] for physical activity energy expenditure = -22.4 [10.17]; p < .05). CONCLUSIONS: Levels of habitual PA are lower in middle-aged and older adults with higher levels of chronic inflammation and greater self-reported fatigue. In addition, participants who experienced greater declines in inflammation during the interventions had greater declines in fatigue and larger increases in PA. PMID- 27382040 TI - Genotoxicity of TiO2 nanoparticles assessed by mini-gel comet assay and micronucleus scoring with flow cytometry. AB - The widespread production and use of nanoparticles calls for faster and more reliable methods to assess their safety. The main aim of this study was to investigate the genotoxicity of three reference TiO2 nanomaterials (NM) within the frame of the FP7-NANoREG project, with a particular focus on testing the applicability of mini-gel comet assay and micronucleus (MN) scoring by flow cytometry. BEAS-2B cells cultured under serum-free conditions were exposed to NM100 (anatase, 50-150nm), NM101 (anatase, 5-8nm) and NM103 (rutile, 20-28nm) for 3, 24 or 48h mainly at concentrations 1-30 MUg/ml. In the mini-gel comet assay (eight gels per slide), we included analysis of (i) DNA strand breaks, (ii) oxidised bases (Fpg-sensitive sites) and (iii) light-induced DNA damage due to photocatalytic activity. Furthermore, MN assays were used and we compared the results of more high-throughput MN scoring with flow cytometry to that of cytokinesis-block MN cytome assay scored manually using a microscope. Various methods were used to assess cytotoxic effects and the results showed in general no or low effects at the doses tested. A weak genotoxic effect of the tested TiO2 materials was observed with an induction of oxidised bases for all three materials of which NM100 was the most potent. When the comet slides were briefly exposed to lab light, a clear induction of DNA strand breaks was observed for the anatase materials, but not for the rutile. This highlights the risk of false positives when testing photocatalytically active materials if light is not properly avoided. A slight increase in MN formation for NM103 was observed in the different MN assays at the lower doses tested (1 and 5 MUg/ml). We conclude that mini-gel comet assay and MN scoring using flow cytometry successfully can be used to efficiently study cytotoxic and genotoxic properties of nanoparticles. PMID- 27382041 TI - Clinical characteristics, functional respiratory decline and follow-up in adult patients with primary ciliary dyskinesia. AB - INTRODUCTION: Primary ciliary dyskinesia (PCD) is a genetic disease characterised by abnormalities in ciliary function, responsible for chronic pulmonary and sinonasal diseases. Adult clinical features and outcome are poorly described. OBJECTIVES: To assess the clinical characteristics and disease progression in adults with PCD. METHODS: Bicentric retrospective study, focusing on adults (>=18 years) with an asserted diagnosis of PCD based on the presence of bronchiectasis with typical ultrastructural defect of cilia and/or situs inversus (SI). Clinical symptoms, respiratory function, extent of bronchiectasis, microbiology and molecular analysis were assessed. Results are expressed as median (25th; 75th centile). RESULTS: 78 patients were included with a median follow-up of 8.1 years. 91% of patients had respiratory symptoms and 95% had chronic rhinosinusitis. Half of ultrastructural defects concerned dynein arms. Respiratory function was significantly lower in women (FEV1=60% predicted (50; 76), vs 77% (62; 95), p=0.009) and in patients with chronic airway Pseudomonas aeruginosa (PA, n=21) infection (FEV1=60% (48; 71) vs 75% (55; 89), p=0.04). FEV1 was associated with gender (regression coefficient for men =13.8, p=0.009), chest CT score (r=-0.42, p<0.001) but not with age at diagnosis, SI or body mass index. FEV1 decline was -13.4 mL/year (-42.8; +11.9) and was greater in women (-29.3 mL/year, (-59.7; -11.9), vs -2.0 mL/year (-26.9; +25.4), p=0.002). Three patients had severe respiratory failure. CONCLUSIONS: Alteration of respiratory function in adults with PCD is heterogeneous and usually moderate but appears more severe in women and in patients with chronic PA infection. Only 4% of patients develop chronic respiratory failure. PMID- 27382042 TI - Evaluation of a corrected implementation of a method of simulating pulmonary nodules in chest tomosynthesis. AB - Background A method of simulating pulmonary nodules in tomosynthesis images has previously been developed and evaluated. An unknown feature of a rounding function included in the computer code was later found to introduce an artifact, affecting simulated nodules in low-signal regions of the images. The computer code has now been corrected. Purpose To perform a thorough evaluation of the corrected nodule-simulation method, comparing the detection rate and visual appearance of artificial nodules with those of real nodules in an observer performance experiment. Material and Methods A cohort of 64 patients with a total of 129 pulmonary nodules was used in the study. Artificial nodules, each matching a corresponding real nodule by size, attenuation, and anatomical location, were generated and simulated into the tomosynthesis images of the different patients. The detection rate and visual appearance of artificial nodules generated using both the corrected and uncorrected computer code were compared to those of real nodules. The results were evaluated using modified receiver operating characteristic (ROC) analyses. Results The difference in detection rate between artificial and real nodules slightly increased using the corrected computer code (uncorrected code: area under the curve [AUC], 0.47; 95% CI, 0.43-0.51; corrected code: AUC, 0.42; 95% CI, 0.38-0.46). The visual appearance was however substantially improved using the corrected computer code (uncorrected code: AUC, 0.70; 95% CI, 0.63-0.76; corrected code: AUC, 0.49; 95% CI, 0.29-0.65). Conclusion The computer code including a correct rounding function generates simulated nodules that are more visually realistic than simulated nodules generated using the uncorrected computer code, but have a slightly different detection rate compared to real nodules. PMID- 27382044 TI - The role of posterior aortopexy in the treatment of left mainstem bronchus compression. AB - OBJECTIVES: We reviewed the role of posterior aortopexy for left mainstem bronchus compression in infants and children. METHODS: Eighteen children with respiratory symptoms were enrolled between 2005 and 2015 for surgical decompression of the left mainstem bronchus. The children were managed from diagnosis to follow-up by a dedicated tracheal team. Primary outcomes were the complete relief of symptoms or improvement with respect to preoperative clinical status. RESULTS: The median age was 4 years (0.3-15.4) and the median weight was 13.2 kg (3, 1-40). Symptoms or indications for bronchoscopy included difficult weaning from mechanical ventilation (n = 3, 17%), difficult weaning from tracheotomy (n = 4, 22%), recurrent pneumonia (n = 4, 22%), wheezing (n = 3, 17%), atelectasis (n = 1, 5.5%), bitonal cough (n = 1, 5.5%) and stridor (n = 2, 11%). Associated malformations were present in 88.7%. The diagnosis was made by bronchoscopy and computed tomography. Indication for surgery was the presence of pulsations and reduction in the diameter of the left mainstem bronchus compression of more than 70%. Surgery was performed by left posterolateral thoracotomy. Aortopexy was done under bronchoscopic control. No early or late deaths were observed, nor were reoperations necessary. Residual malacia was observed in 8 children (44%). Median follow-up was 4.1 years (0.1-7.1). At last follow-up, 17/18 (94.4%) children showed adequate airway patency. CONCLUSIONS: The intrathoracic location of the left mainstem bronchus predisposes it to compression. Vascular anomalies represent the most frequent causes. Aortopexy has been advocated as a safe and useful method to relieve the compression, and our results confirmed these findings. Management of these patients is challenging and requires a multidisciplinary team. PMID- 27382043 TI - Marital Dissolutions and the Health of Older Individuals in a Rural African Context. AB - Objectives : Research from high-income countries has often found a negative relationship between marital dissolutions and health. This paper assesses that relationship among older sub-Saharan Africans, on a now-aging continent. Such individuals are likely to be at risk of a dissolution, or have already experienced one, due to high rates of marriage. Methods : Data from over 1,200 rural Malawians, age 45+, are employed from the 2008 and 2010 waves of the Malawi Longitudinal Study of Families and Health. Cross-sectional and lagged dependent variable regressions examine the relationship between marital dissolutions and 4 measures of self-reported health: retrospective health, relative health (compared with others in one's village), and age-standardized SF-12 mental and physical health scales. Results : Worse relative, mental, and physical health are associated with being currently divorced/widowed compared with being married. However, worse retrospective health is linked to becoming divorced/widowed between 2008 and 2010. Those divorced/widowed prior to 2008, and who remained so through 2010, are in worse relative and physical health. Discussion : The findings question the relative hardship of marital dissolutions for those who have managed to survive into old age, and call for the collection of more detailed longitudinal data on older Africans on this topic. PMID- 27382045 TI - Protection of pulmonary graft from thrombosis in donation after cardiac death: effect of warm ischaemia versus cold ischaemia. AB - OBJECTIVES: The use of donation after cardiac death (DCD) to overcome organ shortage is slowly moving into the clinic. In this study, we compare the protective effect of warm ischaemia versus cold ischaemia on thrombotic formation in non-heparinized pulmonary grafts. METHODS: Twelve Landrace pigs were randomized into two groups: warm ischaemia and cold ischaemia. Ventricular fibrillation without the administration of heparin was induced to mimick an uncontrolled DCD situation. The animals were then exposed to either 1 h of cold ischaemia (insertion of drain and installation of cold fluid in the pleuras) or warm ischaemia (body temperature). After 1 h, the pulmonary artery was opened and the pulmonary arterial branches were then macroscopically studied for thrombotic material. RESULTS: After 60 min, the temperature was 36.6 +/- 0.0 degrees C in the warm ischaemic group and 14.6 +/- 0.1 degrees C in the cold ischaemic group (P < 0.001). In the warm ischaemic group, no thrombotic material could be found in the pulmonary artery in the animals examined and in the cold ischaemic group 6.8 +/- 0.2 ml thrombotic material was found in the pulmonary artery (P < 0.001). In the warm ischaemic group, no thrombotic material could be found in the arterial branches of the pulmonary artery and in the cold ischaemic group 2.3 +/- 0.1 ml thrombotic material was found in the arterial branches of the pulmonary artery (P < 0.001). CONCLUSIONS: Warm ischaemia rather than cold ischaemia seems to protect the pulmonary graft from thrombosis in uncontrolled non-heparinized DCD pigs. PMID- 27382046 TI - Visualization of bronchial circulation at bronchial anastomotic site using bronchial fluorescein angiography technique. AB - OBJECTIVES: Successful bronchial healing after a bronchoplastic procedure mainly depends on bronchial circulation at the anastomostic site. We developed a bronchial fluorescein angiography (B-FAG) technique for visualizing circulation on the bronchial surface. The technique was evaluated in animals. METHODS: Fluorescein was used as a contrast agent and an autofluorescence imaging (AFI) bronchoscope as a detector. The left main pulmonary artery (PA) and main bronchus of 10 pigs were isolated. After transection of the left main bronchus and bronchial arteries and re-anastomosis of the bronchus, the pigs were randomly divided into two groups: the PA- group (n = 5), in which the pulmonary artery was transected; and the PA+ group (n = 5), in which the pulmonary artery was preserved. Following intravenous injection of fluorescein, the distal anastomotic site was observed for 30 min with autofluorescence imaging bronchoscopy. Bronchial specimens sampled 2 days after the surgical intervention were histologically evaluated. RESULTS: In the PA- group, there was no fluorescein enhancement in the distal bronchus throughout the observation time. However, enhancement, which turned the bronchial surface from magenta to bright green, was clearly observed in less than 207 +/- 102.5 s in the PA+ group. The enhancement status detected by bronchial fluorescein angiography was related to the extent of tissue damage, as was proven histologically in the acute healing stage. CONCLUSIONS: Bronchial fluorescein angiography clearly visualized the circulatory status promptly after the anastomosis procedure at the central bronchus. This technique is a potentially practical approach to predict ischaemic airway complications following bronchial anastomosis. PMID- 27382047 TI - Achieving the tobacco endgame: evidence on the hardening hypothesis from repeated cross-sectional studies in New Zealand 2008-2014. AB - INTRODUCTION: The hardening hypothesis proposes that as smoking prevalence declines the proportion of 'hardcore' or 'hardened' smokers will increase. The possible constructs of hardening include reduced motivation to quit, increased levels of addiction, increased levels of disadvantage and reduced quit rates among continuing smokers. Most previous studies have investigated only a single facet of the hypothesis. We used data from a national population monitor to test the hypothesis using measures across all four hardening constructs. METHODS: We analysed data from a biennial population-based survey of New Zealand adults (aged 15 years+) from 2008 to 2014. Data were collected through face-to-face computer assisted personal interviews. RESULTS: During a period of reducing smoking prevalence, there were no statistically significant changes in indicators of hardening including the proportion of smokers who were unmotivated to quit, unable to quit despite repeated attempts or receiving state benefits or on a low income. Quit rates did not change significantly over the study period. For 2014 versus 2008, the OR for recent (within last 1-12 months) quitting was 1.14 (95% CI 0.53 to 2.46) and for sustained (within previous 13-24 months) quitting was 1.88 (95% CI 0.78 to 4.54). CONCLUSIONS: This study provides evidence that robust tobacco control strategies that result in substantial declines in smoking prevalence are not accompanied by the hypothesised increase in 'hardcore' or 'hardened' smokers who are more addicted and less motivated and able to quit. The findings suggest that there is no need for substantial change in approach to achieve New Zealand's Smokefree 2025 goal on the grounds that the smoker population is becoming increasingly hardened. PMID- 27382048 TI - Down-Regulation of Hippocampal Genes Regulating Dopaminergic, GABAergic, and Glutamatergic Function Following Combined Neonatal Phencyclidine and Post-Weaning Social Isolation of Rats as a Neurodevelopmental Model for Schizophrenia. AB - BACKGROUND: Dysfunction of dopaminergic, GABAergic, and glutamatergic function underlies many core symptoms of schizophrenia. Combined neonatal injection of the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP), and post weaning social isolation of rats produces a behavioral syndrome with translational relevance to several core symptoms of schizophrenia. This study uses DNA microarray to characterize alterations in hippocampal neurotransmitter related gene expression and examines the ability of the sodium channel blocker, lamotrigine, to reverse behavioral changes in this model. METHODS: Fifty-four male Lister-hooded rat pups either received phencyclidine (PCP, 10mg/kg, s.c.) on post-natal days (PND) 7, 9, and 11 before being weaned on PND 23 into separate cages (isolation; PCP-SI; n = 31) or received vehicle injection and group-housing (2-4 per cage; V-GH; n = 23) from weaning. The effect of lamotrigine on locomotor activity, novel object recognition, and prepulse inhibition of acoustic startle was examined (PND 60-75) and drug-free hippocampal gene expression on PND 70. RESULTS: Acute lamotrigine (10-15mg/kg i.p.) reversed the hyperactivity and novel object recognition impairment induced by PCP-SI but had no effect on the prepulse inhibition deficit. Microarray revealed small but significant down-regulation of hippocampal genes involved in glutamate metabolism, dopamine neurotransmission, and GABA receptor signaling and in specific schizophrenia-linked genes, including parvalbumin (PVALB) and GAD67, in PCP-SI rats, which resemble changes reported in schizophrenia. CONCLUSIONS: Findings indicate that alterations in dopamine neurotransmission, glutamate metabolism, and GABA signaling may contribute to some of the behavioral deficits observed following PCP-SI, and that lamotrigine may have some utility as an adjunctive therapy to improve certain cognitive deficits symptoms in schizophrenia. PMID- 27382049 TI - AcsF Catalyzes the ATP-dependent Insertion of Nickel into the Ni,Ni-[4Fe4S] Cluster of Acetyl-CoA Synthase. AB - Acetyl-CoA synthase (ACS) catalyzes the reversible condensation of CO, CoA, and a methyl-cation to form acetyl-CoA at a unique Ni,Ni-[4Fe4S] cluster (the A cluster). However, it was unknown which proteins support the assembly of the A cluster. We analyzed the product of a gene from the cluster containing the ACS gene, cooC2 from Carboxydothermus hydrogenoformans, named AcsFCh, and showed that it acts as a maturation factor of ACS. AcsFCh and inactive ACS form a stable 2:1 complex that binds two nickel ions with higher affinity than the individual components. The nickel-bound ACS-AcsFCh complex remains inactive until MgATP is added, thereby converting inactive to active ACS. AcsFCh is a MinD-type ATPase and belongs to the CooC protein family, which can be divided into homologous subgroups. We propose that proteins of one subgroup are responsible for assembling the Ni,Ni-[4Fe4S] cluster of ACS, whereas proteins of a second subgroup mature the [Ni4Fe4S] cluster of carbon monoxide dehydrogenases. PMID- 27382050 TI - Structure and Function of the PriC DNA Replication Restart Protein. AB - Collisions between DNA replication complexes (replisomes) and barriers such as damaged DNA or tightly bound protein complexes can dissociate replisomes from chromosomes prematurely. Replisomes must be reloaded under these circumstances to avoid incomplete replication and cell death. Bacteria have evolved multiple pathways that initiate DNA replication restart by recognizing and remodeling abandoned replication forks and reloading the replicative helicase. In vitro, the simplest of these pathways is mediated by the single-domain PriC protein, which, along with the DnaC helicase loader, can load the DnaB replicative helicase onto DNA bound by the single-stranded DNA (ssDNA)-binding protein (SSB). Previous biochemical studies have identified PriC residues that mediate interactions with ssDNA and SSB. However, the mechanisms by which PriC drives DNA replication restart have remained poorly defined due to the limited structural information available for PriC. Here, we report the NMR structure of full-length PriC from Cronobacter sakazakii PriC forms a compact bundle of alpha-helices that brings together residues involved in ssDNA and SSB binding at adjacent sites on the protein surface. Disruption of these interaction sites and of other conserved residues leads to decreased DnaB helicase loading onto SSB-bound DNA. We also demonstrate that PriC can directly interact with DnaB and the DnaB.DnaC complex. These data lead to a model in which PriC acts as a scaffold for recruiting DnaB.DnaC to SSB/ssDNA sites present at stalled replication forks. PMID- 27382051 TI - Twin Attributes of Tyrosyl-tRNA Synthetase of Leishmania donovani: A HOUSEKEEPING PROTEIN TRANSLATION ENZYME AND A MIMIC OF HOST CHEMOKINE. AB - Aminoacyl-tRNA synthetases (aaRSs) are housekeeping enzymes essential for protein synthesis. Apart from their parent aminoacylation activity, several aaRSs perform non-canonical functions in diverse biological processes. The present study explores the twin attributes of Leishmania tyrosyl-tRNA synthetase (LdTyrRS) namely, aminoacylation, and as a mimic of host CXC chemokine. Leishmania donovani is a protozoan parasite. Its genome encodes a single copy of tyrosyl-tRNA synthetase. We first tested the canonical aminoacylation role of LdTyrRS. The recombinant protein was expressed, and its kinetic parameters were determined by aminoacylation assay. To study the physiological role of LdTyrRS in Leishmania, gene deletion mutations were attempted via targeted gene replacement. The heterozygous mutants showed slower growth kinetics and exhibited attenuated virulence. LdTyrRS appears to be an essential gene as the chromosomal null mutants did not survive. Our data also highlights the non-canonical function of L. donovani tyrosyl-tRNA synthetase. We show that LdTyrRS protein is present in the cytoplasm and exits from the parasite cytoplasm into the extracellular medium. The released LdTyrRS functions as a neutrophil chemoattractant. We further show that LdTyrRS specifically binds to host macrophages with its ELR (Glu-Leu-Arg) peptide motif. The ELR-CXCR2 receptor interaction mediates this binding. This interaction triggers enhanced secretion of the proinflammatory cytokines TNF-alpha and IL-6 by host macrophages. Our data indicates a possible immunomodulating role of LdTyrRS in Leishmania infection. This study provides a platform to explore LdTyrRS as a potential target for drug development. PMID- 27382052 TI - Small Molecule Inhibitors Targeting Tec Kinase Block Unconventional Secretion of Fibroblast Growth Factor 2. AB - Fibroblast growth factor 2 (FGF2) is a potent mitogen promoting both tumor cell survival and tumor-induced angiogenesis. It is secreted by an unconventional secretory mechanism that is based upon direct translocation across the plasma membrane. Key steps of this process are (i) phosphoinositide-dependent membrane recruitment, (ii) FGF2 oligomerization and membrane pore formation, and (iii) extracellular trapping mediated by membrane-proximal heparan sulfate proteoglycans. Efficient secretion of FGF2 is supported by Tec kinase that stimulates membrane pore formation based upon tyrosine phosphorylation of FGF2. Here, we report the biochemical characterization of the direct interaction between FGF2 and Tec kinase as well as the identification of small molecules that inhibit (i) the interaction of FGF2 with Tec, (ii) tyrosine phosphorylation of FGF2 mediated by Tec in vitro and in a cellular context, and (iii) unconventional secretion of FGF2 from cells. We further demonstrate the specificity of these inhibitors for FGF2 because tyrosine phosphorylation of a different substrate of Tec is unaffected in their presence. Building on previous evidence using RNA interference, the identified compounds corroborate the role of Tec kinase in unconventional secretion of FGF2. In addition, they are valuable lead compounds with great potential for drug development aiming at the inhibition of FGF2 dependent tumor growth and metastasis. PMID- 27382053 TI - Thromboxane A2 Activates YAP/TAZ Protein to Induce Vascular Smooth Muscle Cell Proliferation and Migration. AB - The thromboxane A2 receptor (TP) has been implicated in restenosis after vascular injury, which induces vascular smooth muscle cell (VSMC) migration and proliferation. However, the mechanism for this process is largely unknown. In this study, we report that TP signaling induces VSMC migration and proliferation through activating YAP/TAZ, two major downstream effectors of the Hippo signaling pathway. The TP-specific agonists [1S-[1alpha,2alpha(Z),3beta(1E,3S*),4 alpha]]-7 [3-[3-hydroxy-4-(4-iodophenoxy)-1-butenyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5 heptenoic acid (I-BOP) and 9,11-dideoxy-9alpha,11alpha-methanoepoxy-prosta-5Z,13E dien-1-oic acid (U-46619) induce YAP/TAZ activation in multiple cell lines, including VSMCs. YAP/TAZ activation induced by I-BOP is blocked by knockout of the receptor TP or knockdown of the downstream G proteins Galpha12/13 Moreover, Rho inhibition or actin cytoskeleton disruption prevents I-BOP-induced YAP/TAZ activation. Importantly, TP activation promotes DNA synthesis and cell migration in VSMCs in a manner dependent on YAP/TAZ. Taken together, thromboxane A2 signaling activates YAP/TAZ to promote VSMC migration and proliferation, indicating YAP/TAZ as potential therapeutic targets for cardiovascular diseases. PMID- 27382054 TI - Endogenous N-terminal Domain Cleavage Modulates alpha1D-Adrenergic Receptor Pharmacodynamics. AB - The alpha1D-adrenergic receptor (ADRA1D) is a key regulator of cardiovascular, prostate, and central nervous system functions. This clinically relevant G protein-coupled receptor has proven difficult to study, as it must form an obligate modular homodimer containing the PDZ proteins scribble and syntrophin or become retained in the endoplasmic reticulum as non-functional protein. We previously determined that targeted removal of the N-terminal (NT) 79 amino acids facilitates ADRA1D plasma membrane expression and agonist-stimulated functional responses. However, whether such an event occurs in physiological contexts was unknown. Herein, we report the ADRA1D is subjected to innate NT processing in cultured human cells. SNAP near-infrared imaging and tandem-affinity purification revealed the ADRA1D is expressed as both full-length and NT truncated forms in multiple human cell lines. Serial truncation mapping identified the cleavage site as Leu(90)/Val(91) in the 95-amino acid ADRA1D NT domain, suggesting human cells express a Delta1-91 ADRA1D species. Tandem-affinity purification MS/MS and co immunoprecipitation analysis indicate NT processing of ADRA1D is not required to form scribble-syntrophin macromolecular complexes. Yet, label-free dynamic mass redistribution signaling assays demonstrate that Delta1-91 ADRA1D agonist responses were greater than WT ADRA1D. Mutagenesis of the cleavage site nullified the processing event, resulting in ADRA1D agonist responses less than the WT receptor. Thus, we propose that processing of the ADRA1D NT domain is a physiological mechanism employed by cells to generate a functional ADRA1D isoform with optimal pharmacodynamic properties. PMID- 27382055 TI - A Novel Redoxin in the Thylakoid Membrane Regulates the Titer of Photosystem I. AB - In photosynthetic organisms like cyanobacteria and plants, the main engines of oxygenic photosynthesis are the pigment-protein complexes photosystem I (PSI) and photosystem II (PSII) located in the thylakoid membrane. In the cyanobacterium Synechocystis sp. PCC 6803, the slr1796 gene encodes a single cysteine thioredoxin-like protein, orthologs of which are found in multiple cyanobacterial strains as well as chloroplasts of higher plants. Targeted inactivation of slr1796 in Synechocystis 6803 resulted in compromised photoautotrophic growth. The mutant displayed decreased chlorophyll a content. These changes correlated with a decrease in the PSI titer of the mutant cells, whereas the PSII content was unaffected. In the mutant, the transcript levels of genes for PSI structural and accessory proteins remained unaffected, whereas the levels of PSI structural proteins were severely diminished, indicating that Slr1796 acts at a posttranscriptional level. Biochemical analysis indicated that Slr1796 is an integral thylakoid membrane protein. We conclude that Slr1796 is a novel regulatory factor that modulates PSI titer. PMID- 27382056 TI - A Mouse Model for Dietary Xenosialitis: ANTIBODIES TO XENOGLYCAN CAN REDUCE FERTILITY. AB - Humans can incorporate the xenoglycan N-glycolylneuraminic acid (Neu5Gc) from the diet into reproductive tissues and secretions. Most humans also have circulating antibodies specific for this dietary xenoglycan. The potential for inflammation induced by incorporated Neu5Gc and circulating anti-Neu5Gc antibodies, termed xenosialitis, has been discussed as a factor influencing several human diseases. Potential effects of xenosialitis on human fertility remain unknown. Here, we investigate possible adverse effects of the presence of Neu5Gc on sperm or endometrium combined with anti-Neu5Gc antibodies in semen or uterine secretions in a mouse model. We use Cmah(-/-) mice, humanized for Neu5Gc deficiency. We find that the viability, migration, and capacitation of sperm with incorporated Neu5Gc are negatively affected when these are exposed to anti-Neu5Gc antibodies. In addition, we find that after copulation, activated uterine neutrophils and macrophages show increased phagocytosis of sperm in the presence of anti-Neu5Gc antibodies via the complement receptor 3 (C3R) and Fcgamma I/II/III (Fc receptor). Furthermore, Neu5Gc in endometrial cells combined with the presence of anti-Neu5Gc antibodies alters the receptivity and decidualization of endometrial explants. These studies provide mechanistic insights on how Neu5Gc on sperm and/or endometrium combined with anti-Neu5Gc antibodies in semen and uterine fluid might contribute to unexplained human infertility. PMID- 27382057 TI - Chromatin Remodeler Recruitment during Macrophage Differentiation Facilitates Transcription Factor Binding to Enhancers in Mature Cells. AB - We show how enhancers of macrophage-specific genes are rendered accessible in differentiating macrophages to allow their induction in mature cells in response to an appropriate stimulus. Using a lentiviral knockdown approach in primary differentiating macrophages from mouse bone marrow, we demonstrate that enhancers of Il12b and Il1a are kept relatively lowly occupied by nucleosomes and accessible through recruitment of the nucleosome remodeler BAF/PBAF. Our results using an inducible cell line that expresses an estrogen receptor fusion of the macrophage-specific transcription factor PU.1 (PUER) show that BAF/PBAF recruitment to these enhancers is a consequence of translocation of PUER to the nucleus in the presence of tamoxifen, and we speculate that remodeler recruitment may be directly mediated by PU.1. In the absence of BAF/PBAF recruitment, nucleosome occupancy at the enhancer of Il12b (and to a lesser extent at Il1a) reaches high levels in bone marrow-derived macrophages (BMDMs), and the enhancers are not fully cleared of nucleosomes upon LPS induction, resulting in impaired gene expression. Analysis of Il12b expression in single cells suggests that recruitment of the remodeler is necessary for high levels of transcription from the same promoter, and we propose that remodelers function by increasing nucleosome turnover to facilitate transcription factor over nucleosome binding in a process we have termed "remodeler-assisted competition." PMID- 27382058 TI - Preferential Protection of Genetic Fidelity within Open Chromatin by the Mismatch Repair Machinery. AB - Epigenetic systems are well known for the roles they play in regulating the differential expression of the same genome in different cell types. However, epigenetic systems can also directly impact genomic integrity by protecting genetic sequences. Using an experimental evolutionary approach, we studied rates of mutation in the fission yeast Schizosaccharomyces pombe strains that lacked genes encoding several epigenetic regulators or mismatch repair components. We report that loss of a functional mismatch repair pathway in S. pombe resulted in the preferential enrichment of mutations in euchromatin, indicating that the mismatch repair machinery preferentially protected genetic fidelity in euchromatin. This preference is probably determined by differences in the accessibility of chromatin at distinct chromatin regions, which is supported by our observations that chromatin accessibility positively correlated with mutation rates in S. pombe or human cancer samples with deficiencies in mismatch repair. Importantly, such positive correlation was not observed in S. pombe strains or human cancer samples with functional mismatch repair machinery. PMID- 27382059 TI - Identification of Components of the SUMOylation Machinery in Candida glabrata: ROLE OF THE DESUMOYLATION PEPTIDASE CgUlp2 IN VIRULENCE. AB - Regulation of protein function by reversible post-translational modification, SUMOylation, is widely conserved in the eukaryotic kingdom. SUMOylation is essential for cell growth, division, and adaptation to stress in most organisms, including fungi. As these are key factors in determination of fungal virulence, in this study, we have investigated the importance of SUMOylation in the human pathogen, Candida glabrata We identified the enzymes involved in small ubiquitin like modifier conjugation and show that there is strong conservation between Saccharomyces cerevisiae and C. glabrata We demonstrate that SUMOylation is an essential process and that adaptation to stress involves changes in global SUMOylation in C. glabrata Importantly, loss of the deSUMOylating enzyme CgUlp2 leads to highly reduced small ubiquitin-like modifier protein levels, and impaired growth, sensitivity to multiple stress conditions, reduced adherence to epithelial cells, and poor colonization of specific tissues in mice. Our study thus demonstrates a key role for protein SUMOylation in the life cycle and pathobiology of C. glabrata. PMID- 27382060 TI - Electrophysiological Signature of Homomeric and Heteromeric Glycine Receptor Channels. AB - Glycine receptors are chloride-permeable, ligand-gated ion channels and contribute to the inhibition of neuronal firing in the central nervous system or to facilitation of neurotransmitter release if expressed at presynaptic sites. Recent structure-function studies have provided detailed insights into the mechanisms of channel gating, desensitization, and ion permeation. However, most of the work has focused only on comparing a few isoforms, and among studies, different cellular expression systems were used. Here, we performed a series of experiments using recombinantly expressed homomeric and heteromeric glycine receptor channels, including their splice variants, in the same cellular expression system to investigate and compare their electrophysiological properties. Our data show that the current-voltage relationships of homomeric channels formed by the alpha2 or alpha3 subunits change upon receptor desensitization from a linear to an inwardly rectifying shape, in contrast to their heteromeric counterparts. The results demonstrate that inward rectification depends on a single amino acid (Ala(254)) at the inner pore mouth of the channels and is closely linked to chloride permeation. We also show that the current voltage relationships of glycine-evoked currents in primary hippocampal neurons are inwardly rectifying upon desensitization. Thus, the alanine residue Ala(254) determines voltage-dependent rectification upon receptor desensitization and reveals a physio-molecular signature of homomeric glycine receptor channels, which provides unprecedented opportunities for the identification of these channels at the single cell level. PMID- 27382061 TI - An Expanded CAG Repeat in Huntingtin Causes +1 Frameshifting. AB - Maintenance of triplet decoding is crucial for the expression of functional protein because deviations either into the -1 or +1 reading frames are often non functional. We report here that expression of huntingtin (Htt) exon 1 with expanded CAG repeats, implicated in Huntington pathology, undergoes a sporadic +1 frameshift to generate from the CAG repeat a trans-frame AGC repeat-encoded product. This +1 recoding is exclusively detected in pathological Htt variants, i.e. those with expanded repeats with more than 35 consecutive CAG codons. An atypical +1 shift site, UUC C at the 5' end of CAG repeats, which has some resemblance to the influenza A virus shift site, triggers the +1 frameshifting and is enhanced by the increased propensity of the expanded CAG repeats to form a stem-loop structure. The +1 trans-frame-encoded product can directly influence the aggregation of the parental Htt exon 1. PMID- 27382062 TI - The Effect of Fragmented Pathogenic alpha-Synuclein Seeds on Prion-like Propagation. AB - Aggregates of abnormal proteins are widely observed in neuronal and glial cells of patients with various neurodegenerative diseases, and it has been proposed that prion-like behavior of these proteins can account for not only the onset but also the progression of these diseases. However, it is not yet clear which abnormal protein structures function most efficiently as seeds for prion-like propagation. In this study, we aimed to identify the most pathogenic species of alpha-synuclein (alpha-syn), the main component of the Lewy bodies and Lewy neurites that are observed in alpha-synucleinopathies. We prepared various forms of alpha-syn protein and examined their seeding properties in vitro in cells and in mouse experimental models. We also characterized these alpha-syn species by means of electron microscopy and thioflavin fluorescence assays and found that fragmented beta sheet-rich fibrous structures of alpha-syn with a length of 50 nm or less are the most efficient promoters of accumulation of phosphorylated alpha syn, which is the hallmark of alpha-synucleinopathies. These results indicate that fragmented amyloid-like aggregates of short alpha-syn fibrils are the key pathogenic seeds that trigger prion-like conversion. PMID- 27382063 TI - Structural and Functional Role of Acetyltransferase hMOF K274 Autoacetylation. AB - Many histone acetyltransferases undergo autoacetylation, either through chemical or enzymatic means, to potentiate enzymatic cognate substrate lysine acetylation, although the mode and molecular role of such autoacetylation is poorly understood. The MYST family of histone acetyltransferases is autoacetylated at an active site lysine residue to facilitate cognate substrate lysine binding and acetylation. Here, we report on a detailed molecular investigation of Lys-274 autoacetylation of the human MYST protein Males Absent on the First (hMOF). A mutational scan of hMOF Lys-274 reveals that all amino acid substitutions of this residue are able to bind cofactor but are significantly destabilized, both in vitro and in cells, and are catalytically inactive for cognate histone H4 peptide lysine acetylation. The x-ray crystal structure of a hMOF K274P mutant suggests that the reduced stability and catalytic activity stems from a disordering of the residue 274-harboring a alpha2-beta7 loop. We also provide structural evidence that a C316S/E350Q mutant, which is defective for cognate substrate lysine acetylation; and biochemical evidence that a K268M mutant, which is defective for Lys-274 chemical acetylation in the context of a K274-peptide, can still undergo quantitative K274 autoacetylation. Together, these studies point to the critical and specific role of hMOF Lys-274 autoacetylation in hMOF stability and cognate substrate acetylation and argues that binding of Ac-CoA to hMOF likely drives Lys 274 autoacetylation for subsequent cognate substrate acetylation. PMID- 27382064 TI - Toward Understanding Functional Properties and Subunit Arrangement of alpha4beta2delta gamma-Aminobutyric Acid, Type A (GABAA) Receptors. AB - GABAA receptors are pentameric ligand-gated channels mediating inhibitory neurotransmission in the CNS. alpha4betaxdelta GABAA receptors are extrasynaptic receptors important for tonic inhibition. The functional properties and subunit arrangement of these receptors are controversial. We predefined subunit arrangement by using subunit concatenation. alpha4, beta2, and delta subunits were concatenated to dimeric, trimeric, and, in some cases, pentameric subunits. We constructed in total nine different receptor pentamers in at least two different ways and expressed them in Xenopus oocytes. The delta subunit was substituted in any of the five positions in the alpha1beta2 receptor. In addition, we investigated all receptors with the 2:2:1 subunit stoichiometry for alpha4, beta2, and delta. Several functional receptors were obtained. Interestingly, all of these receptors had very similar EC50 values for GABA in the presence of the neurosteroid 3alpha, 21-dihydroxy-5alpha-pregnan-20-one (THDOC). All functional receptors containing delta subunits were sensitive to 4 chloro-N-[2-(2-thienyl)imidazo[1,2-a]pyridin-3-yl]benzamide (DS2). Moreover, none of the receptors was affected by ethanol up to 30 mm These properties recapitulate those of non-concatenated receptors expressed from a cRNA ratio of 1:1:5 coding for alpha4, beta2, and delta subunits. We conclude that the subunit arrangement of alpha4beta2delta GABAA receptors is not strongly predefined but is mostly satisfying the 2:2:1 subunit stoichiometry for alpha4, beta2, and delta subunits and that several subunit arrangements result in receptors with similar functional properties tuned to physiological conditions. PMID- 27382065 TI - High-temperature single-molecule kinetic analysis of thermophilic archaeal MCM helicases. AB - The minichromosome maintenance (MCM) complex is the replicative helicase responsible for unwinding DNA during archaeal and eukaryal genome replication. To mimic long helicase events in the cell, a high-temperature single-molecule assay was designed to quantitatively measure long-range DNA unwinding of individual DNA helicases from the archaeons Methanothermobacter thermautotrophicus (Mth) and Thermococcus sp. 9 degrees N (9 degrees N). Mth encodes a single MCM homolog while 9 degrees N encodes three helicases. 9 degrees N MCM3, the proposed replicative helicase, unwinds DNA at a faster rate compared to 9 degrees N MCM2 and to Mth MCM. However, all three MCM proteins have similar processivities. The implications of these observations for DNA replication in archaea and the differences and similarities among helicases from different microorganisms are discussed. Development of the high-temperature single-molecule assay establishes a system to comprehensively study thermophilic replisomes and evolutionary links between archaeal, eukaryal, and bacterial replication systems. PMID- 27382066 TI - Human CDK18 promotes replication stress signaling and genome stability. AB - Cyclin-dependent kinases (CDKs) coordinate cell cycle checkpoints with DNA repair mechanisms that together maintain genome stability. However, the myriad mechanisms that can give rise to genome instability are still to be fully elucidated. Here, we identify CDK18 (PCTAIRE 3) as a novel regulator of genome stability, and show that depletion of CDK18 causes an increase in endogenous DNA damage and chromosomal abnormalities. CDK18-depleted cells accumulate in early S phase, exhibiting retarded replication fork kinetics and reduced ATR kinase signaling in response to replication stress. Mechanistically, CDK18 interacts with RAD9, RAD17 and TOPBP1, and CDK18-deficiency results in a decrease in both RAD17 and RAD9 chromatin retention in response to replication stress. Importantly, we demonstrate that these phenotypes are rescued by exogenous CDK18 in a kinase-dependent manner. Collectively, these data reveal a rate-limiting role for CDK18 in replication stress signalling and establish it as a novel regulator of genome integrity. PMID- 27382067 TI - Binding properties of YjeQ (RsgA), RbfA, RimM and Era to assembly intermediates of the 30S subunit. AB - Our understanding regarding the function of YjeQ (also called RsgA), RbfA, RimM and Era in ribosome biogenesis has been derived in part from the study of immature 30S particles that accumulate in null strains lacking one of these factors. However, their mechanistic details are still unknown. Here, we demonstrate that these immature particles are not dead-end products of assembly, but progress into mature 30S subunits. Mass spectrometry analysis revealed that in vivo the occupancy level of these factors in these immature 30S particles is below 10% and that the concentration of factors does not increase when immature particles accumulate in cells. We measured by microscale thermophoresis that YjeQ and Era binds to the mature 30S subunit with high affinity. However, the binding affinity of these factors to the immature particles and of RimM and RbfA to mature or immature particles was weak, suggesting that binding is not occurring at physiological concentrations. These results suggest that in the absence of these factors, the immature particles evolve into a thermodynamically stable intermediate that exhibits low affinity for the assembly factors. These results imply that the true substrates of YjeQ, RbfA, RimM and Era are immature particles that precede the ribosomal particles accumulating in the knockouts strains. PMID- 27382068 TI - Editorial: CRISPR in Nucleic Acids Research. PMID- 27382070 TI - Next-generation RNA-based fluorescent biosensors enable anaerobic detection of cyclic di-GMP. AB - Bacteria occupy a diverse set of environmental niches with differing oxygen availability. Anaerobic environments such as mammalian digestive tracts and industrial reactors harbor an abundance of both obligate and facultative anaerobes, many of which play significant roles in human health and biomanufacturing. Studying bacterial function under partial or fully anaerobic conditions, however, is challenging given the paucity of suitable live-cell imaging tools. Here, we introduce a series of RNA-based fluorescent biosensors that respond selectively to cyclic di-GMP, an intracellular bacterial second messenger that controls cellular motility and biofilm formation. We demonstrate the utility of these biosensors in vivo under both aerobic and anaerobic conditions, and we show that biosensor expression does not interfere with the native motility phenotype. Together, our results attest to the effectiveness and versatility of RNA-based fluorescent biosensors, priming further development and application of these and other analogous sensors to study host-microbial and microbial-microbial interactions through small molecule signals. PMID- 27382073 TI - D2 Region of the 28S RNA Gene: A Too-Conserved Fragment for Inferences on Phylogeny of South American Triatomines. AB - The brasiliensis complex is composed of five triatomine species, and different approaches suggest that Triatoma lenti and Triatoma petrochiae may be the new members. Therefore, this study sought to analyze the phylogenetic relationships within this complex by means of the D2 region of the 28S RNA gene, and to analyze the degree of polymorphism and phylogenetic significance of this gene for South American triatomines. Phylogenetic analysis by using sequence fragments of the D2 domain did not allow to perform phylogenetic inferences on species within the brasiliensis complex, because the gene alignment composed of a matrix with 37 specimens exhibited only two variable sites along the 567 base pairs used. Furthermore, if all South American species are included, only four variable sites were detected, reflecting the high degree of gene conservation. Therefore, we do not recommend the use of this gene for phylogenetic reconstruction for this group of Chagas disease vectors. PMID- 27382069 TI - HOXA1 binds RBCK1/HOIL-1 and TRAF2 and modulates the TNF/NF-kappaB pathway in a transcription-independent manner. AB - HOX proteins define a family of key transcription factors regulating animal embryogenesis. HOX genes have also been linked to oncogenesis and HOXA1 has been described to be active in several cancers, including breast cancer. Through a proteome-wide interaction screening, we previously identified the TNFR-associated proteins RBCK1/HOIL-1 and TRAF2 as HOXA1 interactors suggesting that HOXA1 is functionally linked to the TNF/NF-kappaB signaling pathway. Here, we reveal a strong positive correlation between expression of HOXA1 and of members of the TNF/NF-kappaB pathway in breast tumor datasets. Functionally, we demonstrate that HOXA1 can activate NF-kappaB and operates upstream of the NF-kappaB inhibitor IkappaB. Consistently, we next demonstrate that the HOXA1-mediated activation of NF-kappaB is non-transcriptional and that RBCK1 and TRAF2 influences on NF-kappaB are epistatic to HOXA1. We also identify an 11 Histidine repeat and the homeodomain of HOXA1 to be required both for RBCK1 and TRAF2 interaction and NF kappaB stimulation. Finally, we highlight that activation of NF-kappaB is crucial for HOXA1 oncogenic activity. PMID- 27382074 TI - The National Institutes of Health Fogarty International Center Global Health Scholars and Fellows Program: Collaborating Across Five Consortia to Strengthen Research Training. AB - As demand for global health research training continues to grow, many universities are striving to meet the needs of trainees in a manner complementary to research priorities of the institutions hosting trainees, while also increasing capacity for conducting research. We provide an overview of the first 4 years of the Global Health Program for Fellows and Scholars, a collaboration of 20 U.S. universities and institutions spread across 36 low- and middle-income countries funded through the National Institutes of Health Fogarty International Center. We highlight many aspects of our program development that may be of interest to other multinational consortia developing global health research training programs. PMID- 27382075 TI - AutoSyP: A Low-Cost, Low-Power Syringe Pump for Use in Low-Resource Settings. AB - This article describes the design and evaluation of AutoSyP, a low-cost, low power syringe pump intended to deliver intravenous (IV) infusions in low-resource hospitals. A constant-force spring within the device provides mechanical energy to depress the syringe plunger. As a result, the device can run on rechargeable battery power for 66 hours, a critical feature for low-resource settings where the power grid may be unreliable. The device is designed to be used with 5- to 60 mL syringes and can deliver fluids at flow rates ranging from 3 to 60 mL/hour. The cost of goods to build one AutoSyP device is approximately $500. AutoSyP was tested in a laboratory setting and in a pilot clinical study. Laboratory accuracy was within 4% of the programmed flow rate. The device was used to deliver fluid to 10 healthy adult volunteers and 30 infants requiring IV fluid therapy at Queen Elizabeth Central Hospital in Blantyre, Malawi. The device delivered fluid with an average mean flow rate error of -2.3% +/- 1.9% for flow rates ranging from 3 to 60 mL/hour. AutoSyP has the potential to improve the accuracy and safety of IV fluid delivery in low-resource settings. PMID- 27382076 TI - Reannotation of Yersinia pestis Strain 91001 Based on Omics Data. AB - Yersinia pestis is among the most dangerous human pathogens, and systematic research of this pathogen is important in bacterial pathogenomics research. To fully interpret the biological functions, physiological characteristics, and pathogenesis of Y. pestis, a comprehensive annotation of its entire genome is necessary. The emergence of omics-based research has brought new opportunities to better annotate the genome of this pathogen. Here, the complete genome of Y. pestis strain 91001 was reannotated using genomics and proteogenomics data. One hundred and thirty-seven unreliable coding sequences were removed, and 41 homologous genes were relocated with their translational initiation sites, while the functions of seven pseudogenes and 392 hypothetical genes were revised. Moreover, annotations of noncoding RNAs, repeat sequences, and transposable elements have also been incorporated. The reannotated results are freely available at http://tody.bmi.ac.cn. PMID- 27382077 TI - Health-Care Workers' Perspectives on Ebola Virus Vaccine: A Focus Group and In Depth Interview Interventional Study. AB - Health-care workers (HCWs) will require Ebola virus vaccine (EVV) when it is introduced because of the high risk of exposure to the disease. Evaluations of factors that facilitate or limit vaccine uptake are critical for a successful vaccine program. Nigerian HCWs were interviewed to evaluate their knowledge, levels of acceptance, determinants of acceptance, and willingness to pay for EVV. The significance level was set at P <= 0.05. None of the 193 participating HCWs had correct knowledge of EVV; 34.7% (67/193) of workers thought that EVV was an extract of the serum of Ebola virus patients. About 77.3% (51/66) of workers in a region that reported Ebola cases (Lagos) were willing to be vaccinated, compared with 4.7% (3/61) in Enugu and 13.6% (9/66) in Abia (P = 0.0001). After health education, the proportion of HCWs willing to receive EVV increased (P = 0.006) except for doctors (P < 0.1). The percentage of HCWs willing to pay for EVV was 86.4%, 72.1%, and 59% in Lagos, Enugu, and Abia, respectively. The workers had fears about EVV based on nonfactual assumptions. Therefore, the EVV introduction strategy should include a strong awareness campaign with adequate explanation about the content of EVV. PMID- 27382078 TI - Human Pulmonary Infection by the Zoonotic Metastrongylus salmi Nematode. The First Reported Case in the Americas. AB - Pulmonary metastrongylosis, a zoonotic disease found primarily in pigs, is caused by eight different species of the cosmopolitan nematode Metastrongylus genus. To date, only four human cases have been reported, all from Europe. Herein, a severe case of pulmonary infection caused by Metastrongylus salmi in an Ecuadorian man, with successful treatment with ivermectin, is described. PMID- 27382079 TI - Clinical Features and Transmission Pattern of Hepatitis A: An Experience from a Hepatitis A Outbreak Caused by Two Cocirculating Genotypes in Sri Lanka. AB - Sri Lanka is one of the intermediate-endemic areas for hepatitis A virus (HAV), and concerns exist about the increasing HAV-susceptible population. In fact, Sri Lanka recorded a large hepatitis outbreak, possibly hepatitis A, around the end of the Sri Lankan war. It included more than 14,000 patients consisting of local residents, internally displaced personnel, and military personnel in the main combat zone. The outbreak had slowed down by October 2009; however, acute viral hepatitis continued to occur sequentially among military personnel. We obtained clinical information and serum samples from 222 patients with acute hepatitis who visited the Military Hospital Anuradhapura between January and September 2010. Samples were subjected to laboratory testing including HAV-immunoglobulin M and genotyping. Most patients (98.2%) were confirmed as having hepatitis A belonging to two subgenotypes: IA and IIIA. We did not observe any differences in clinical or biochemical features among patients with subgenotypes IA and IIIA except for pale stools and upper abdominal discomfort. During the investigation period, we observed a serial outbreak caused by identical HAV strains with an interval in line with that of typical HAV incubation periods. Most patients in the first outbreak were found in the training center, and patients in the second outbreak were found in multiple places where soldiers were assigned after the training center. These findings indicate that a strain of HAV diffused from one place to another along with movement of infected persons among the HAV-susceptible population. HAV vaccination for high-risk groups, such as young soldiers, is necessary. PMID- 27382080 TI - Diarrheagenic Escherichia coli: Prevalence and Pathotype Distribution in Children from Peruvian Rural Communities. AB - Diarrheagenic Escherichia coli (DEC) are common pathogens of childhood gastrointestinal infections worldwide. To date, research tracking DEC has mainly been completed in urban areas. This study aims to determine the prevalence and pathotype distribution of DEC strains in children from rural Peruvian communities and to establish their association with malnutrition. In this prospective cohort, 93 children aged 6-13 months from rural communities of Urubamba (Andes) and Moyobamba (jungle) were followed for 6 months. Diarrheal and control stool samples were analyzed using multiplex real-time polymerase chain reaction to identify the presence of virulence genes of DEC strains. The overall isolation rate of DEC was 43.0% (352/820). Enteroaggregative E. coli (EAEC, 20.4%), enteropathogenic E. coli (EPEC, 14.2%), and diffusely aggregative E. coli (DAEC, 11.0%) were the most prevalent pathotypes. EAEC was more frequently found in Moyobamba samples (P < 0.01). EPEC was the only strain significantly more frequent in diarrheal than asymptomatic control samples (P < 0.01). DEC strains were more prevalent among younger children (aged 6-12 months, P < 0.05). A decline in height-for-age Z-score (HAZ) was observed in 75.7% of children overall. EAEC was more frequently isolated among children who had a greater HAZ decline (P < 0.05). In conclusion, DEC strains were frequently found in stool samples from children in rural communities of the highlands and jungle of Peru. In addition, children with a greater decline in their growth rate had higher EAEC isolation rates, highlighting the importance of this pathogen in child malnutrition. PMID- 27382081 TI - Spatiotemporal Analysis of Malaria in Urban Ahmedabad (Gujarat), India: Identification of Hot Spots and Risk Factors for Targeted Intervention. AB - The world population, especially in developing countries, has experienced a rapid progression of urbanization over the last half century. Urbanization has been accompanied by a rise in cases of urban infectious diseases, such as malaria. The complexity and heterogeneity of the urban environment has made study of specific urban centers vital for urban malaria control programs, whereas more generalizable risk factor identification also remains essential. Ahmedabad city, India, is a large urban center located in the state of Gujarat, which has experienced a significant Plasmodium vivax and Plasmodium falciparum disease burden. Therefore, a targeted analysis of malaria in Ahmedabad city was undertaken to identify spatiotemporal patterns of malaria, risk factors, and methods of predicting future malaria cases. Malaria incidence in Ahmedabad city was found to be spatially heterogeneous, but temporally stable, with high spatial correlation between species. Because of this stability, a prediction method utilizing historic cases from prior years and seasons was used successfully to predict which areas of Ahmedabad city would experience the highest malaria burden and could be used to prospectively target interventions. Finally, spatial analysis showed that normalized difference vegetation index, proximity to water sources, and location within Ahmedabad city relative to the dense urban core were the best predictors of malaria incidence. Because of the heterogeneity of urban environments and urban malaria itself, the study of specific large urban centers is vital to assist in allocating resources and informing future urban planning. PMID- 27382082 TI - Five-Year Eradication of Hepatitis B Infection After an Outreach Immunization Program in the Waorani Population in the Ecuadorian Amazon. AB - In Waorani communities of the Amazon basin of Ecuador, hepatitis B (HB) surface antigen was found in 14% of asymptomatic persons. The aim of this study was to identify the Waorani population in Ecuador and obtain an epidemiologically adequate coverage of vaccination against hepatitis B virus (HBV) among them. Between February and September 2010, three vaccination campaigns were completed as part of a collaborative activity between the Ecuadorian Ministry of Public Health and the community leaders in the intervention areas. In addition, in 10 of the 22 Waorani communities, during first contact, a questionnaire about risk factors for HBV infection was administered. A total of 16 Waorani communities were registered before the beginning of this intervention, but during the actual process, six additional communities were identified. In total, 1,251 community members were registered, 92.7% of which received all three doses of the vaccine. Among them, 83% of survey respondents reported having been vaccinated, but only 22% were able to show proof. Only 1% of respondents were intravenous drug users, whereas 22% had at least one tattoo. All self-identified as heterosexual, but only 32% reported using condoms during sexual intercourse. By March 2015, no new cases of HB were been reported in any of the Waorani communities. Herein, we report the importance of intersectoral collaboration to strengthen health interventions in an isolated population like the Waorani area. PMID- 27382084 TI - Overrepresentation of Diabetes in Soft Tissue Nontuberculous Mycobacterial Infections. AB - Diabetes predisposes patients to bacterial infections. Although diabetes confers susceptibility to tuberculosis, the association between nontuberculous mycobacterial (NTM) infections and diabetes remains unknown. A retrospective chart analysis of patients in northern Australia during a 20-year period with soft tissue NTM infections revealed that patients with diabetes were three times overrepresented in comparison to the general population (odds ratio = 3.13). There was a statistically significant association between NTM infections and diabetes in this patient cohort (P = 0.0082). PMID- 27382083 TI - Molecular and Serological Evidence of Leishmania Infection in Stray Dogs from Visceral Leishmaniasis-Endemic Areas of Bangladesh. AB - Visceral leishmaniasis (VL), or kala-azar, is mainly caused by two closely related Leishmania species, Leishmania infantum and Leishmania donovani Leishmania infantum is responsible for zoonotic VL, with dogs as the main reservoir host in the Mediterranean, the Middle East, Asia, and South America. In the Indian subcontinent, VL is caused by L. donovani and is considered anthroponotic, although the only known vector, the sand fly, is zoophilic in nature. The role of domestic and stray dogs in VL transmission is still unclear in this area. We screened 50 stray dogs from VL-endemic areas of Bangladesh for serological and molecular evidence of Leishmania infection. We detected anti Leishmania antibodies in six (12%) dog serum samples using rK39 immunochromatographic tests. We observed Leishmania kinetoplast DNA in 10 (20%) buffy coat DNA samples by real-time polymerase chain reaction (PCR), five of which were positive based on internal transcribed spacer 1-PCR. A sequencing analysis of the amplified products confirmed that the parasitic DNA was derived from L. donovani Our findings support the hypothesis that stray dogs are an animal reservoir for L. donovani in this endemic region. Further studies are required to determine the precise role of dogs in the epidemiology of VL in Bangladesh. PMID- 27382086 TI - Development and Validation of Quality Indicators on Continuing Care for Patients With AUD: A Delphi Study. AB - AIMS: To develop indicators to assess quality of continuing care for persons with alcohol use disorder (AUD). METHODS: A guideline-based RAND-modified Delphi method was used to develop and validate indicators regarding the process and outcome of continuing care. We systematically searched for evidence-based guidelines and existing quality indicators. A multidisciplinary expert panel prioritized recommendations using a written questionnaire followed by a group discussion. Important recommendations were then translated to quality indicators. The panel subsequently selected indicators that were measurable and applicable in Belgium. In a final round the indicators face-validity was assessed. RESULTS: We extracted 69 recommendations from 06 guidelines and 17 relevant quality indicators. Of all, 13 indicators remained after 03 written rounds and 02 group discussions. CONCLUSIONS: This study describes a systematic approach to develop and validate quality indicators for continuing care for AUD. The final set of selected indicators consisted of 10 process and 03 outcome indicators. As the level of evidence of effective continuing care components is very low further development of the indicators is recommended. SHORT SUMMARY: This study describes a systematic approach to develop and validate quality indicators for continuing care for AUD. The proposed set of indicators consisted of 10 process and 03 outcome indicators. As the level of evidence of effective continuing care components is very low further development of the indicators is recommended. PMID- 27382085 TI - NADPH Oxidase Plays a Role on Ethanol-Induced Hypertension and Reactive Oxygen Species Generation in the Vasculature. AB - AIMS: Investigate the role of NADPH oxidase on ethanol-induced hypertension and vascular oxidative stress. METHODS: Male Wistar rats were treated with ethanol (20% v/v). RESULTS: Apocynin (10 mg/kg/day, i.p.) prevented ethanol-induced hypertension. The increased contractility of endothelium-intact and endothelium denuded aortic rings from ethanol-treated rats to phenylephrine was prevented by apocynin. Ethanol consumption increased superoxide anion (O2 (-)) generation and lipid peroxidation and apocynin prevented these responses. The decrease on plasma and vascular nitrate/nitrite (NOx) levels induced by ethanol was not prevented by apocynin. Treatment with ethanol did not affect aortic levels of hydrogen peroxide (H2O2) or reduced glutathione (GSH). Ethanol did not alter the activities of xanthine oxidase (XO), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Ethanol increased the expression of Nox1, PKCdelta, nNOS, SAPK/JNK and SOD2 in the rat aorta and apocynin prevented these responses. No difference on aortic expression of Nox2, Nox4, p47phox, Nox organizer 1 (Noxo1), eNOS and iNOS was detected after treatment with ethanol. Ethanol treatment did not alter the phosphorylation of SAPK/JNK, p38MAPK, c-Src, Rac1 or PKCdelta. CONCLUSIONS: The major new finding of our study is that the increased vascular generation of reactive oxygen species (ROS) induced by ethanol is related to increased vascular Nox1/NADPH oxidase expression. This mechanism is involved in vascular dysfunction and hypertension induced by ethanol. Additionally, we conclude that ethanol consumption induces the expression of different proteins that regulate vascular contraction and growth and that NADPH oxidase-derived ROS play a role in such response. SHORT SUMMARY: The key findings of our study are that ethanol-induced hypertension is mediated by NADPH oxidase. Moreover, increased vascular Nox1 expression is related to the generation of reactive oxygen species (ROS) by ethanol. Finally, ROS induced by ethanol increase the expression of the regulatory vascular proteins. PMID- 27382088 TI - Preventative Measures. PMID- 27382087 TI - Long-Term Persistence of Newly Initiated Warfarin Therapy in Chinese Patients With Nonvalvular Atrial Fibrillation. AB - BACKGROUND: Despite its therapeutic efficacy, warfarin is extremely underused in Chinese patients with nonvalvular atrial fibrillation (AF). Whether the nonpersistence of warfarin treatment contributes to its underuse is not known. The aims of this study were to determine nonpersistence rates of newly started warfarin treatment in Chinese patients with nonvalvular AF and to identify the factors associated with discontinuation of the treatment. METHODS AND RESULTS: We identified 1461 patients with nonvalvular AF enrolled in the Chinese Atrial Fibrillation Registry (CAFR) who newly started on warfarin therapy in the period between August 1, 2011, and June 30, 2014. During a follow-up of 426+/-232 days, 22.1% of patients discontinued warfarin within 3 months, 44.4% within 1 year, and 57.6% within 2 years of initiation of therapy. Patients with no or partial insurance coverage had a higher likelihood to discontinue warfarin than those with full insurance coverage (adjusted hazard ratio 1.65, 95% confidence interval [1.03-2.64]; P=0.038 and 1.66 [1.13-2.42]; P=0.009, respectively). Paroxysmal AF (1.56 [1.28-1.92]; P<0.0001), no prior stroke/transient ischemic attack/thromboembolism (1.60 [1.24-2.05]; P=0.0003), and no dyslipidemia (1.34 [1.06-1.70]; P=0.016) were also found to be independent predictors for nonpersistence of warfarin therapy. CONCLUSIONS: Nonpersistence of warfarin treatment becomes a serious problem for stroke prevention in Chinese patients with nonvalvular AF. Our findings can be used to identify patients who require closer attention or to develop better management strategy for oral anticoagulation therapy. PMID- 27382089 TI - Optimal Levels of All Major Cardiovascular Risk Factors in Younger Age and Functional Disability in Older Age: The Chicago Heart Association Detection Project in Industry 32-Year Follow-Up Health Survey. AB - BACKGROUND: The associations of optimal levels of all major cardiovascular disease risk factors, that is, low risk, in younger age with subsequent cardiovascular disease morbidity and mortality have been well documented. However, little is known about associations of low-risk profiles in younger age with functional disability in older age. METHODS AND RESULTS: The sample included 6014 participants from the Chicago Heart Association Detection Project in Industry Study. Low-risk status, defined as untreated systolic/diastolic blood pressure <=120/<=80 mm Hg, untreated serum total cholesterol <5.18 mmol/l, not smoking, body mass index < 25 kg/m(2), and no diabetes mellitus, was assessed at baseline (1967 to 1973). Functional disability, categorized as (1) any disability in activities of daily living (ADLs), (2) any disability in instrumental ADLs but not in ADL, or (3) no disability, was assessed from the 2003 health survey. There were 39% women, 4% Black, with a mean age of 43 years and 6% low-risk status at baseline. After 32 years, 7% reported having limitations in performing any ADL and 11% in any instrumental ADL only. The prevalence of any ADL limitation was lowest in low-risk people and increased in a graded fashion with less-favorable risk factor groups (P trend <0.001). Compared with those with 2+ high-risk factors, the multivariable-adjusted odds of having any disability in ADLs versus no disability in people with low risk, any moderate risk, and 1 high-risk factor at baseline were lower by 58%, 48%, and 37%, respectively. Results were similar for instrumental ADLs, in both men and women. CONCLUSIONS: Having an optimal cardiovascular disease risk factor profile at younger age is associated with the lowest rate of functional disability in older age. PMID- 27382090 TI - Baseline Hemodynamics and Response to Contrast Media During Diagnostic Cardiac Catheterization Predict Adverse Events in Heart Failure Patients. AB - BACKGROUND: Contrast media administered during cardiac catheterization can affect hemodynamic variables. However, little is documented about the effects of contrast on hemodynamics in heart failure patients or the prognostic value of baseline and changes in hemodynamics for predicting subsequent adverse events. METHODS AND RESULTS: In this prospective study of 150 heart failure patients, we measured hemodynamics at baseline and after administration of iodixanol or iopamidol contrast. One-year Kaplan-Meier estimates of adverse event-free survival (death, heart failure hospitalization, and rehospitalization) were generated, grouping patients by baseline measures of pulmonary capillary wedge pressure (PCWP) and cardiac index (CI), and by changes in those measures after contrast administration. We used Cox proportional hazards modeling to assess sequentially adding baseline PCWP and change in CI to 5 validated risk models (Seattle Heart Failure Score, ESCAPE [Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness], CHARM [Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity], CORONA [Controlled Rosuvastatin Multinational Trial in Heart Failure], and MAGGIC [Meta Analysis Global Group in Chronic Heart Failure]). Median contrast volume was 109 mL. Both contrast media caused similarly small but statistically significant changes in most hemodynamic variables. There were 39 adverse events (26.0%). Adverse event rates increased using the composite metric of baseline PCWP and change in CI (P<0.01); elevated baseline PCWP and decreased CI after contrast correlated with the poorest prognosis. Adding both baseline PCWP and change in CI to the 5 risk models universally improved their predictive value (P<=0.02). CONCLUSIONS: In heart failure patients, the administration of contrast causes small but significant changes in hemodynamics. Calculating baseline PCWP with change in CI after contrast predicts adverse events and increases the predictive value of existing models. Patients with elevated baseline PCWP and decreased CI after contrast merit greatest concern. PMID- 27382091 TI - Endocrine Abnormalities in Aging Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study. AB - PURPOSE: The development of endocrinopathies in survivors of childhood cancer as they age remains understudied. We characterized endocrine outcomes in aging survivors from the Childhood Cancer Survivor Study on the basis of therapeutic exposures. PATIENTS AND METHODS: We analyzed self-reported conditions in 14,290 5 year survivors from the Childhood Cancer Survivor Study, with a median age 6 years (range, < 1 to 20 years) at diagnosis and 32 years (range, 5 to 58 years) at last follow-up. Identification of high-risk therapeutic exposures was adopted from the Children's Oncology Group Long-Term Follow-Up Guidelines. Cumulative incidence curves and prevalence estimates quantified and regression models compared risks of primary hypothyroidism, hyperthyroidism, thyroid neoplasms, hypopituitarism, obesity, diabetes mellitus, or gonadal dysfunction between survivors and siblings. RESULTS: The cumulative incidence and prevalence of endocrine abnormalities increased across the lifespan of survivors (P < .01 for all). Risk was significantly higher in survivors exposed to high-risk therapies compared with survivors not so exposed for primary hypothyroidism (hazard ratio [HR], 6.6; 95% CI, 5.6 to 7.8), hyperthyroidism (HR, 1.8; 95% CI, 1.2 to 2.8), thyroid nodules (HR, 6.3; 95% CI, 5.2 to 7.5), thyroid cancer (HR, 9.2; 95% CI, 6.2 to 13.7), growth hormone deficiency (HR, 5.3; 95% CI, 4.3 to 6.4), obesity (relative risk, 1.8; 95% CI, 1.7 to 2.0), and diabetes mellitus (relative risk, 1.9; 95% CI, 1.6 to 2.4). Women exposed to high-risk therapies had six-fold increased risk for premature ovarian insufficiency (P < .001), and men demonstrated higher prevalence of testosterone replacement (P < .001) after cyclophosphamide equivalent dose of 20 g/m(2) or greater or testicular irradiation with 20 Gy or greater. Survivors demonstrated an increased risk for all thyroid disorders and diabetes mellitus regardless of treatment exposures compared with siblings (P < .001 for all). CONCLUSION: Endocrinopathies in survivors increased substantially over time, underscoring the need for lifelong subspecialty follow-up of those at risk. PMID- 27382092 TI - Choice of Surgical Procedure for Patients With Non-Small-Cell Lung Cancer <= 1 cm or > 1 to 2 cm Among Lobectomy, Segmentectomy, and Wedge Resection: A Population Based Study. AB - PURPOSE: According to the lung cancer staging project, T1a (<= 2 cm) non-small cell lung cancer (NSCLC) should be additionally classified into <= 1 cm and > 1 to 2 cm groups. This study aimed to investigate the surgical procedure for NSCLC <= 1 cm and > 1 to 2 cm. METHODS: We identified 15,760 patients with T1aN0M0 NSCLC after surgery from the Surveillance, Epidemiology, and End Results database. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared among patients after lobectomy, segmentectomy, or wedge resection. The proportional hazards model was applied to evaluate multiple prognostic factors. RESULTS: OS and LCSS favored lobectomy compared with segmentectomy or wedge resection in patients with NSCLC <= 1 cm and > 1 to 2 cm. Multivariable analysis showed that segmentectomy and wedge resection were independently associated with poorer OS and LCSS than lobectomy for NSCLC <= 1 cm and > 1 to 2 cm. With sublobar resection, lower OS and LCSS emerged for NSCLC > 1 to 2 cm after wedge resection, whereas similar survivals were observed for NSCLC <= 1 cm. Multivariable analyses showed that wedge resection is an independent risk factor of survival for NSCLC > 1 to 2 cm but not for NSCLC <= 1 cm. CONCLUSION: Lobectomy showed better survival than sublobar resection for patients with NSCLC <= 1 cm and > 1 to 2 cm. For patients in whom lobectomy is unsuitable, segmentectomy should be recommended for NSCLC > 1 to 2 cm, whereas surgeons could rely on surgical skills and the patient profile to decide between segmentectomy and wedge resection for NSCLC <= 1 cm. PMID- 27382094 TI - Moving Programmed Death-1 Inhibitors to the Front Lines in Non-Small-Cell Lung Cancer. PMID- 27382095 TI - Evolving Role of the Estrogen Receptor as a Predictive Biomarker: ESR1 Mutational Status and Endocrine Resistance in Breast Cancer. PMID- 27382093 TI - BRAF Mutation Correlates With High-Risk Langerhans Cell Histiocytosis and Increased Resistance to First-Line Therapy. AB - PURPOSE: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia with a broad spectrum of clinical manifestations and outcomes in children. The somatic BRAF(V600E) mutation occurs frequently, but clinical significance remains to be determined. PATIENTS AND METHODS: BRAF(V600E) mutation was investigated in a French LCH cohort. We analyzed associations between mutation status and clinical presentation, extent of disease, reactivation rate, response to therapy, and long-term permanent sequelae. RESULTS: Among 315 patients with successfully determined BRAF status, 173 (54.6%) carried a BRAF(V600E) mutation. Patients with BRAF(V600E) manifested more severe disease than did those with wild-type BRAF. Patients with BRAF(V600E) comprised 87.8% of patients (43 of 49) with multisystem LCH with risk organ involvement (liver, spleen, hematology), 68.6% of patients (35 of 51) with multisystem LCH without risk organ involvement, 43.9% of patients (86 of 196) with single-system LCH, and 42.1% of patients (8 of 19) with lung involved LCH (P < .001). BRAF(V600E) mutation was also associated with organ involvement that could lead to permanent, irreversible damage, such as neurologic (75%) and pituitary (72.9%) injuries. Compared with patients with wild-type BRAF, patients with BRAF(V600E) more commonly displayed resistance to combined vinblastine and corticosteroid therapy (21.9% v 3.3%; P = .001), showed a higher reactivation rate (5-year reactivation rate, 42.8% v 28.1%; P = .006), and had more permanent, long-term consequences from disease or treatment (27.9% v 12.6%; P = .001). CONCLUSION: In children with LCH, BRAF(V600E) mutation was associated with high-risk features, permanent injury, and poor short-term response to chemotherapy. Further population-based studies should be undertaken to confirm our observations and to assess the impact of BRAF inhibitors for this subgroup of patients who may benefit from targeted therapy. PMID- 27382096 TI - Bendamustine in Combination With Gemcitabine and Vinorelbine Is an Effective Regimen As Induction Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma: Final Results of a Multicenter Phase II Study. AB - PURPOSE: This multicenter, open-label, phase II study evaluated the combination of bendamustine, gemcitabine, and vinorelbine (BeGEV) as induction therapy before autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (HL). PATIENTS AND METHODS: Patients with HL who were refractory to or had relapsed after one previous chemotherapy line were eligible. The primary end point was complete response (CR) rate after four cycles of therapy. Secondary end points were: overall response rate, stem-cell mobilization activity, and toxicity. Progression-free and overall survival were also evaluated. RESULTS: In total, 59 patients were enrolled. After four cycles of therapy, 43 patients (73%) achieved CR, and six (10%) achieved partial response, for an overall response rate of 83%. The most common grade 3 to 4 nonhematologic toxicities included febrile neutropenia (n = 7) and infection (n = 4). Regarding hematologic toxicities, grade 3 to 4 thrombocytopenia and neutropenia were each experienced by eight patients (13.5%). CD34+ cells were successfully harvested in 55 of 57 evaluable patients, and 43 of 49 responding patients underwent ASCT. With a median follow-up of 29 months, the 2-year progression-free and overall survival rates for the total population were 62.2% and 77.6%, respectively. The same figures for patients undergoing autograft were 80.8% and 89.3%, respectively. CONCLUSION: This phase II study demonstrates that BeGEV is an effective salvage regimen able to induce CR in a high proportion of patients with relapsed or refractory HL before ASCT. These data provide a strong rationale for further development of the BeGEV regimen. PMID- 27382097 TI - Innovations in American Society of Clinical Oncology Practice Guideline Development. AB - Since the beginning of its guidelines program in 1993, ASCO has continually sought ways to produce a greater number of guidelines while maintaining its commitment to using the rigorous development methods that minimize the biases that threaten the validity of practice recommendations. ASCO is implementing a range of guideline development and implementation innovations. In this article, we describe innovations that are designed to (1) integrate consideration of multiple chronic conditions into practice guidelines; (2) keep more of its guidelines current by applying evolving signals or (more) rapid, for-cause updating approaches; (3) increase the number of high-quality guidelines available to its membership through endorsement and adaptation of other groups' products; (4) improve coverage of its members' guideline needs through a new topic nomination process; and (5) enhance dissemination and promote implementation of ASCO guidelines in the oncology practice community through a network of volunteer ambassadors. We close with a summary of ASCO's plans to facilitate the integration of data from its rapid learning system, CancerLinQ, into ASCO guidelines and to develop tactics through which guideline recommendations can be embedded in clinicians' workflow in digital form. We highlight the challenges inherent in reconciling the need to provide clinicians with more interactive, point-of-care guidance with ASCO's abiding commitment to methodologic rigor in guideline development. PMID- 27382098 TI - CALGB 80403 (Alliance)/E1206: A Randomized Phase II Study of Three Chemotherapy Regimens Plus Cetuximab in Metastatic Esophageal and Gastroesophageal Junction Cancers. AB - PURPOSE: To determine the optimal chemotherapy backbone for testing in future US cooperative group studies for metastatic esophageal and gastroesophageal junction cancers. Cetuximab was added to each treatment arm based on promising preclinical data. PATIENTS AND METHODS: Patients with previously untreated metastatic esophageal or gastroesophageal junction cancer were randomly assigned at a one-to one-to-one ratio to epirubicin, cisplatin, and continuous-infusion fluorouracil (ECF), irinotecan plus cisplatin (IC), or FOLFOX (oxaliplatin, leucovorin, and bolus and infusional fluorouracil). All treatment programs included cetuximab once per week. The primary end point was response rate. Secondary outcomes included overall survival, progression-free survival, time to treatment failure, and safety. As prespecified, primary and secondary analyses were conducted only among patients with adenocarcinoma. RESULTS: This study randomly assigned 245 patients, including 222 with adenocarcinoma. Among patients with adenocarcinoma, response rate was 60.9% (95% CI, 47.9 to 72.8) for ECF plus cetuximab, 45.0% (95% CI, 33.0 to 57.0) for IC plus cetuximab, and 54.3% (95% CI, 42.0 to 66.2) for FOLFOX plus cetuximab. Median overall survival was 11.6, 8.6, and 11.8 months; median progression-free survival was 7.1, 4.9, and 6.8 months; and median time to treatment failure was 5.6, 4.3, and 6.7 months for each of these arms, respectively. FOLFOX plus cetuximab required fewer treatment modifications compared with ECF plus cetuximab and IC plus cetuximab (P = .013), and fewer patients were removed from treatment because of an adverse event or experienced treatment-related death. CONCLUSION: In combination with cetuximab, ECF and FOLFOX had similar efficacy, but FOLFOX was better tolerated. Although differences were nonsignificant, IC plus cetuximab seemed to be the least effective and most toxic of the three regimens tested. PMID- 27382099 TI - Considering Bone Marrow Blasts From Nonerythroid Cellularity Improves the Prognostic Evaluation of Myelodysplastic Syndromes. AB - PURPOSE: WHO classification of myeloid malignancies is based mainly on the percentage of bone marrow (BM) blasts. This is considered from total nucleated cells (TNCs), unless there is erythroid-hyperplasia (erythroblasts >= 50%), calculated from nonerythroid cells (NECs). In these instances, when BM blasts are >= 20%, the disorder is classified as erythroleukemia, and when BM blasts are < 20%, as myelodysplastic syndrome (MDS). In the latter, the percentage of blasts is considered from TNCs. PATIENTS AND METHODS: We assessed the percentage of BM blasts from TNCs and NECs in 3,692 patients with MDS from the Grupo Espanol de Sindromes Mielodisplasicos, 465 patients with erythroid hyperplasia (MDS-E) and 3,227 patients without erythroid hyperplasia. We evaluated the relevance of both quantifications on classification and prognostication. RESULTS: By enumerating blasts systematically from NECs, 22% of patients with MDS-E and 12% with MDS from the whole series diagnosed within WHO categories with < 5% BM blasts, were reclassified into higher-risk categories and showed a poorer overall survival than did those who remained in initial categories (P = .006 and P = .001, respectively). Following WHO recommendations, refractory anemia with excess blasts (RAEB)-2 diagnosis is not possible in MDS-E, as patients with 10% to < 20% BM blasts from TNCs fulfill erythroleukemia criteria; however, by considering blasts from NECs, 72 patients were recoded as RAEB-2 and showed an inferior overall survival than did patients with RAEB-1 without erythroid hyperplasia. Recalculating the International Prognostic Scoring System by enumerating blasts from NECs in MDS-E and in the overall MDS population reclassified approximately 9% of lower-risk patients into higher-risk categories, which indicated the survival expected for higher-risk patients. CONCLUSION: Regardless of the presence of erythroid hyperplasia, calculating the percentage of BM blasts from NECs improves prognostic assessment of MDS. This fact should be considered in future WHO classification reviews. PMID- 27382100 TI - CNS International Prognostic Index: A Risk Model for CNS Relapse in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP. AB - PURPOSE: To develop and validate a risk score for relapse in the CNS in patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: A total of 2,164 patients (18 to 80 years old) with aggressive B-cell lymphomas (80% DLBCL) treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like chemotherapy, who were enrolled in studies from the German High Grade Non-Hodgkin Lymphoma Study Group and the MabThera International Trial, were analyzed for occurrence of relapse/progression in the CNS. The resulting risk model was validated in an independent data set of 1,597 patients with DLBCL identified in the British Columbia Cancer Agency Lymphoid Cancer database. RESULTS: The risk model consists of the International Prognostic Index (IPI) factors in addition to involvement of kidneys and/or adrenal glands (CNS-IPI). In a three-risk group model, the low-risk group (46% of all patients analyzed), the intermediate-risk group (41%), and the high-risk group (12%) showed 2-year rates of CNS disease of 0.6% (CI, 0% to 1.2%), 3.4% (CI, 2.2% to 4.4%), and 10.2% (CI, 6.3% to 14.1%), respectively. Patients from the validation British Columbia Cancer Agency data set showed similar rates of CNS disease for low-risk (0.8%; CI, 0.0% to 1.6%), intermediate-risk (3.9%; CI, 2.3% to 5.5%), and high-risk (12.0%; CI, 7.9% to 16.1%) groups. CONCLUSION: The CNS-IPI is a robust, highly reproducible tool that can be used to estimate the risk of CNS relapse/progression in patients with DLBCL treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Close to 90% of patients with DLBCL belong to the low- and intermediate-risk groups and have a CNS relapse risk < 5%; they may be spared any diagnostic and therapeutic intervention. In contrast, those in the high-risk group have a > 10% risk of CNS relapse and should be considered for CNS-directed investigations and prophylactic interventions. PMID- 27382101 TI - Management and Care of Women With Invasive Cervical Cancer: ASCO Resource Stratified Clinical Practice Guideline. PMID- 27382102 TI - How Eye-Preserving Therapy Affects Long-Term Overall Survival in Heritable Retinoblastoma Survivors. AB - PURPOSE: Intraocular retinoblastoma is curable, but survivors with a heritable predisposition are at high risk for second malignancies. Because second malignancies are associated with high mortality, prognostic factors for second malignancy influence long-term overall survival. This study investigates the impact of all types of eye-preserving therapies on long-term survival in the complete German cohort of patients with heritable retinoblastoma. PATIENTS AND METHODS: Overall survival, disease staging using international scales, time period of diagnosis, and treatment type were analyzed in the 633 German children treated at the national reference center for heritable retinoblastoma. RESULTS: The 5-year overall survival of children diagnosed in Germany with heritable retinoblastoma between 1940 and 2008 was 93.2% (95% CI, 91.2% to 95.1%), but long term mortality was increased compared with patients with nonheritable disease. Overall survival correlated with tumor staging, and 92% of patients were diagnosed with a favorable tumor stage (International Retinoblastoma Staging System stage 0 or I). Despite a 5-year overall survival of 97.4% (95% CI, 96.0% to 98.8%) in patients with stage 0 or I, only 79.5% (95% CI, 74.2% to 84.8%) of these patients survived 40 years after diagnosis. Long-term overall survival was reduced in children treated with eye-preserving radiotherapy compared with enucleation alone, and adding chemotherapy aggravated this effect. CONCLUSION: The benefits of preserving vision must be balanced with the impact of eye preserving treatments on long-term survival in heritable retinoblastoma, and the genetic background of the patient influences choice of eye-preserving treatment. Germline RB1 genetic analysis is important to identify heritable retinoblastoma among unilateral retinoblastoma cases. Eye-preserving radiotherapy should be carefully considered in patients with germline RB1 mutations. Life-long oncologic follow-up is crucial for all retinoblastoma survivors, and less detrimental eye preserving therapies must be developed. PMID- 27382103 TI - The Sound of Silence: A Proxy for Platinum Toxicity. PMID- 27382104 TI - Continued Risk of Relapse Independent of Treatment Modality in Limited-Stage Diffuse Large B-Cell Lymphoma: Final and Long-Term Analysis of Southwest Oncology Group Study S8736. AB - PURPOSE: Utility of combined-modality therapy for patients with limited-stage diffuse large B-cell lymphoma (DLBCL) was shown in the Southwest Oncology Group (SWOG) S8736 study, where three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus radiotherapy (CHOP3RT) improved 5-year progression-free (PFS) and overall survival (OS) compared with eight cycles of CHOP (CHOP8). Subsequent analysis showed an unexpected overlap of the PFS curves. We aimed to confirm and investigate this observation by performing long-term analysis of SWOG S8736 and evaluating these data alongside data from similar patients receiving rituximab and CHOP3RT (SWOG S0014 study). PATIENTS AND METHODS: A subset of patients with limited-stage DLBCL randomly assigned to CHOP8 (n = 150) or CHOP3RT (n = 158) in S8736 was analyzed along with a 56-patient subset treated in S0014 for long-term PFS and OS. RESULTS: Median follow-up in S8736 was 17.7 years. In patients receiving CHOP8 and CHOP3RT, median PFS was 12.0 (95% CI, 8.8 to 14.3) and 11.1 years (95% CI, 8.9 to 14.4), respectively. There were no statistically significant differences in PFS between the groups (P = .73). Median OS was 13.0 (95% CI, 10.4 to 15.2) and 13.7 years (95% CI, 11.1 to 19.4) for patients treated with CHOP8 and CHOP3RT, respectively. Similarly, there were no statistically significant differences in OS between the groups (P = .38). With a median follow-up time 12 years in S0014, 5- and 10-year OS were 82% and 67%, respectively, with a persistent pattern of relapse despite the addition of rituximab. CONCLUSION: Although 5-year PFS and OS were improved after early analysis in patients with limited-stage DLBCL receiving CHOP3RT versus CHOP8, extended survival data showed similar PFS and OS, with continuous treatment failure. The addition of rituximab (S0014) to combined-modality therapy did not mitigate the continued relapse risk, underscoring the value of prolonged clinical trial patient observation and possible unique biology of limited-stage DLBCL. PMID- 27382106 TI - Congenital Heart Disease Epidemiology in the United States: Blindly Feeling for the Charging Elephant. PMID- 27382105 TI - Congenital Heart Defects in the United States: Estimating the Magnitude of the Affected Population in 2010. AB - BACKGROUND: Because of advancements in care, there has been a decline in mortality from congenital heart defects (CHDs) over the past several decades. However, there are no current empirical data documenting the number of people living with CHDs in the United States. Our aim was to estimate the CHD prevalence across all age groups in the United States in the year 2010. METHODS: The age-, sex-, and severity-specific observed prevalence of CHDs in Quebec, Canada, in the year 2010 was assumed to equal the CHD prevalence in the non-Hispanic white population in the United States in 2010. A race-ethnicity adjustment factor, reflecting differential survival between racial-ethnic groups through 5 years of age for individuals with a CHD and that in the general US population, was applied to the estimated non-Hispanic white rates to derive CHD prevalence estimates among US non-Hispanic blacks and Hispanics. Confidence intervals for the estimated CHD prevalence rates and case counts were derived from a combination of Taylor series approximations and Monte Carlo simulation. RESULTS: We estimated that ~2.4 million people (1.4 million adults, 1 million children) were living with CHDs in the United States in 2010. Nearly 300 000 of these individuals had severe CHDs. CONCLUSIONS: Our estimates highlight the need for 2 important efforts: planning for health services delivery to meet the needs of the growing population of adults with CHD and the development of surveillance data across the life span to provide empirical estimates of the prevalence of CHD across all age groups in the United States. PMID- 27382110 TI - Editorial: Nucleic Acids Research annual Web Server Issue in 2016. PMID- 27382111 TI - Urine peptidome analysis predicts risk of end-stage renal disease and reveals proteolytic pathways involved in autosomal dominant polycystic kidney disease progression. AB - Background: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by slowly progressive bilateral renal cyst growth ultimately resulting in loss of kidney function and end-stage renal disease (ESRD). Disease progression rate and age at ESRD are highly variable. Therapeutic interventions therefore require early risk stratification of patients and monitoring of disease progression in response to treatment. Methods: We used a urine peptidomic approach based on capillary electrophoresis-mass-spectrometry (CE-MS) to identify potential biomarkers reflecting the risk for early progression to ESRD in the Consortium of Radiologic Imaging in Polycystic Kidney Disease (CRISP) cohort. Results: A biomarker-based classifier consisting of 20 urinary peptides allowed the prediction of ESRD within 10-13 years of follow-up in patients 24-46 years of age at baseline. The performance of the biomarker score approached that of height adjusted total kidney volume (htTKV) and the combination of the biomarker panel with htTKV improved prediction over either one alone. In young patients (<24 years at baseline), the same biomarker model predicted a 30 mL/min/1.73 m 2 glomerular filtration rate decline over 8 years. Sequence analysis of the altered urinary peptides and the prediction of the involved proteases by in silico analysis revealed alterations in distinct proteolytic pathways, in particular matrix metalloproteinases and cathepsins. Conclusion: We developed a urinary test that accurately predicts relevant clinical outcomes in ADPKD patients and suggests altered proteolytic pathways involved in disease progression. PMID- 27382112 TI - Why cellular communication during plant reproduction is particularly mediated by CRP signalling. AB - Secreted cysteine-rich peptides (CRPs) represent one of the main classes of signalling peptides in plants. Whereas post-translationally modified small non CRP peptides (psNCRPs) are mostly involved in signalling events during vegetative development and interactions with the environment, CRPs are overrepresented in reproductive processes including pollen germination and growth, self incompatibility, gamete activation and fusion as well as seed development. In this opinion paper we compare the involvement of both types of peptides in vegetative and reproductive phases of the plant lifecycle. Besides their conserved cysteine pattern defining structural features, CRPs exhibit hypervariable primary sequences and a rapid evolution rate. As a result, CRPs represent a pool of highly polymorphic signalling peptides involved in species specific functions during reproduction and thus likely represent key players to trigger speciation in plants by supporting reproductive isolation. In contrast, precursers of psNCRPs are proteolytically processed into small functional domains with high sequence conservation and act in more general processes. We discuss parallels in downstream processes of CRP signalling in both reproduction and defence against pathogenic fungi and alien pollen tubes, with special emphasis on the role of ROS and ion channels. In conclusion we suggest that CRP signalling during reproduction in plants has evolved from ancient defence mechanisms. PMID- 27382113 TI - Stress-induced flowering: the third category of flowering response. AB - The switch from vegetative growth to reproductive growth, i.e. flowering, is the critical event in a plant's life. Flowering is regulated either autonomously or by environmental factors; photoperiodic flowering, which is regulated by the duration of the day and night periods, and vernalization, which is regulated by low temperature, have been well studied. Additionally, it has become clear that stress also regulates flowering. Diverse stress factors can induce or accelerate flowering, or inhibit or delay it, in a wide range of plant species. This article focuses on the positive regulation of flowering via stress, i.e. the induction or acceleration of flowering in response to stress that is known as stress-induced flowering - a new category of flowering response. This review aims to clarify the concept of stress-induced flowering and to summarize the full range of characteristics of stress-induced flowering from a predominately physiological perspective. PMID- 27382114 TI - Two tomato GDP-D-mannose epimerase isoforms involved in ascorbate biosynthesis play specific roles in cell wall biosynthesis and development. AB - GDP-D-mannose epimerase (GME, EC 5.1.3.18) converts GDP-D-mannose to GDP-L galactose, and is considered to be a central enzyme connecting the major ascorbate biosynthesis pathway to primary cell wall metabolism in higher plants. Our previous work demonstrated that GME is crucial for both ascorbate and cell wall biosynthesis in tomato. The aim of the present study was to investigate the respective role in ascorbate and cell wall biosynthesis of the two SlGME genes present in tomato by targeting each of them through an RNAi-silencing approach. Taken individually SlGME1 and SlGME2 allowed normal ascorbate accumulation in the leaf and fruits, thus suggesting the same function regarding ascorbate. However, SlGME1 and SlGME2 were shown to play distinct roles in cell wall biosynthesis, depending on the tissue considered. The RNAi-SlGME1 plants harbored small and poorly seeded fruits resulting from alterations of pollen development and of pollination process. In contrast, the RNAi-SlGME2 plants exhibited vegetative growth delay while fruits remained unaffected. Analysis of SlGME1- and SlGME2 silenced seeds and seedlings further showed that the dimerization state of pectin rhamnogalacturonan-II (RG-II) was altered only in the RNAi-SlGME2 lines. Taken together with the preferential expression of each SlGME gene in different tomato tissues, these results suggest sub-functionalization of SlGME1 and SlGME2 and their specialization for cell wall biosynthesis in specific tomato tissues. PMID- 27382116 TI - Role of hepatic macrophages in alcoholic liver disease. AB - Alcohol consumption can lead to the increase in gut permeability and cause the translocation of bacteria-derived lipopolysaccharides from the gut to the liver, which subsequently activates immune responses. In this process, macrophages play a critical role and involve in the pathogenesis of alcoholic liver disease (ALD). To define the mechanism underpinning the function of macrophages, it is important to conduct extensive studies to further explicate the phenotypic diversity of macrophages in the context of ALD. In this review, the role of hepatic macrophages in the pathogenesis of ALD is discussed. PMID- 27382115 TI - Volumetric relationship between 2-hydroxyglutarate and FLAIR hyperintensity has potential implications for radiotherapy planning of mutant IDH glioma patients. AB - BACKGROUND: Gliomas with mutant isocitrate dehydrogenase (IDH) produce high levels of 2-hydroxyglutarate (2HG) that can be quantitatively measured by 3D magnetic resonance spectroscopic imaging (MRSI). Current glioma MRI primarily relies upon fluid-attenuated inversion recovery (FLAIR) hyperintensity for treatment planning, although this lacks specificity for tumor cells. Here, we investigated the relationship between 2HG and FLAIR in mutant IDH glioma patients to determine whether 2HG mapping is valuable for radiotherapy planning. METHODS: Seventeen patients with mutant IDH1 gliomas were imaged by 3 T MRI. A 3D MRSI sequence was employed to specifically image 2HG. FLAIR imaging was performed using standard clinical protocol. Regions of interest (ROIs) were determined for FLAIR and optimally thresholded 2HG hyperintensities. The overlap, displacement, and volumes of 2HG and FLAIR ROIs were calculated. RESULTS: In 8 of 17 (47%) patients, the 2HG volume was larger than FLAIR volume. Across the entire cohort, the mean volume of 2HG was 35.3 cc (range, 5.3-92.7 cc), while the mean volume of FLAIR was 35.8 cc (range, 6.3-140.8 cc). FLAIR and 2HG ROIs had mean overlap of 0.28 (Dice coefficients range, 0.03-0.57) and mean displacement of 12.2 mm (range, 3.2-23.5 mm) between their centers of mass. CONCLUSIONS: Our results indicate that for a substantial number of patients, the 2HG volumetric assessment of tumor burden is more extensive than FLAIR volume. In addition, there is only partial overlap and asymmetric displacement between the centers of FLAIR and 2HG ROIs. These results may have important implications for radiotherapy planning of IDH mutant glioma. PMID- 27382117 TI - Living in a material world: tumor-treating fields at the top of the charts. PMID- 27382118 TI - To diet or not to diet - that is still the question. PMID- 27382122 TI - Is intensive care monitoring necessary after coil embolization of unruptured intracranial aneurysms? AB - INTRODUCTION: Patients with an unruptured intracranial aneurysm treated with coil embolization are routinely admitted to the intensive care unit (ICU) after the procedure; however, this practice is questionable. The purpose of this study was to determine if routine admission to the ICU is necessary for patients undergoing coil embolization of an unruptured intracranial aneurysm. METHODS: We conducted a retrospective cohort study of all patients undergoing elective endovascular treatment of an unruptured intracranial aneurysm between 2005 and 2012 at our institution. Multivariate regression analysis was performed to identify predictors of outcome. Cost savings analysis compared ICU admission to step-down or telemetry unit admission. RESULTS: 311 unruptured intracranial aneurysms were treated by coil embolization (190), balloon remodeling (13), or stent-assisted coiling (108). Eleven (3.5%) neurologic complications were noted; 5 (1.6%) of these were permanent. Multivariate regression analysis identified female sex (p=0.028), hypercoagulability (p=0.021), aneurysm size >2 cm (p=0.003), and intraoperative rupture (p<0.001) as predictors of a post-procedural neurologic complication. Cost savings were 57% for admission to a step-down unit and 32% for admission to a telemetry unit compared with ICU admission. CONCLUSIONS: Neurologic complications are rare in the treatment of unruptured intracranial aneurysms, suggesting that routine ICU admission after treatment may not be necessary. Female sex, history of hypercoagulability, aneurysm size >2 cm, and an intraprocedural rupture were predictive of a postoperative complication. ICU monitoring in these subgroups may therefore be warranted. PMID- 27382123 TI - Concomitant aneurysm detection in an intracranial dolichoectasia mouse model using a MicroFil polymer perfusion technique. AB - OBJECTIVE: To assess the feasibility of using MicroFil polymer perfusion to detect concomitant saccular aneurysms in an intracranial arterial dolichoectasia (IADE) model in mice, and to report detailed histomorphometric features of these aneurysms. MATERIALS AND METHODS: IADE models were created in C57/BL6 mice via microsurgical injection of 25 mU elastase into the cisterna magna. The cerebral vasculature was perfused with MicroFil polymer and harvested at 1, 3, and 7 days, and 2 and 4 weeks (n=8 for each group). IADE was defined by a tortuosity index >10 combined with a 25% increase in diameter of the A1 segment of the anterior cerebral artery (ACA), internal carotid artery (ICA), or basilar artery compared with the baseline of controls, which received heat-inactivated elastase. Saccular aneurysm occurrence rate, location, and morphological parameters were investigated using macroscopic and microscopic analysis. RESULTS: IADE was present in 95% (36/38) of the subjects, with a mortality rate of 5% (2/40). Fifteen concomitant saccular aneurysms were detected in 8 (21%) of the 38 surviving mice, including 6 at the posterior communicating artery, 1 along the ACA, 2 along the anterior communicating artery complex, 3 along the ICA, and 3 along the middle cerebral artery. Rupture was confirmed in two aneurysms. Histological examination indicated that the aneurysms develop via arterial-wall remodelling, which is characterized by internal elastic lamina disruptions and muscular layer discontinuity in the media. CONCLUSIONS: The proportion of subjects developing saccular aneurysms in addition to IADE in our mouse model is similar to the 15% of patients with IADE who have concomitant saccular aneurysms. PMID- 27382120 TI - Updates in the management of brain metastases. AB - The clinical management/understanding of brain metastases (BM) has changed substantially in the last 5 years, with key advances and clinical trials highlighted in this review. Several of these changes stem from improvements in systemic therapy, which have led to better systemic control and longer overall patient survival, associated with increased time at risk for developing BM. Development of systemic therapies capable of preventing BM and controlling both intracranial and extracranial disease once BM are diagnosed is paramount. The increase in use of stereotactic radiosurgery alone for many patients with multiple BM is an outgrowth of the desire to employ treatments focused on local control while minimizing cognitive effects associated with whole brain radiotherapy. Complications from BM and their treatment must be considered in comprehensive patient management, especially with greater awareness that the majority of patients do not die from their BM. Being aware of significant heterogeneity in prognosis and therapeutic options for patients with BM is crucial for appropriate management, with greater attention to developing individual patient treatment plans based on predicted outcomes; in this context, recent prognostic models of survival have been extensively revised to incorporate molecular markers unique to different primary cancers. PMID- 27382124 TI - Endovascular thrombectomy for M2 occlusions: comparison between forced arterial suction thrombectomy and stent retriever thrombectomy. AB - BACKGROUND: To date there has been no direct comparison of two frequently used endovascular thrombectomy (EVT) methods (forced arterial suction thrombectomy (FAST) and stent retriever thrombectomy) in M2 occlusions. We review our experiences with EVT performed using FAST and stent retriever thrombectomy in such cases. METHODS: The subjects comprised 41 patients with an M2 occlusion who underwent EVT (25 with FAST, 16 with stent retriever thrombectomy). The patients' data were retrospectively analyzed to evaluate the technical characteristics and angiographic outcome of the two EVT techniques. RESULTS: Thrombolysis In Cerebral Infarction (TICI) grades 2b-3 using the first chosen technique did not differ significantly between the two techniques (FAST 64.0% vs stent retriever thrombectomy 81.2%, p=0.305). Time from groin puncture to reperfusion was significantly shorter for stent retriever thrombectomy (53.0 vs 38.5 min; p=0.045). Distal embolization occurred in three cases (12.0%) in the FAST group and in four (26.7%) in the stent retriever group (p=0.362). However, the two techniques did not differ significantly in the final TICI 2b-3 rate (72.0% vs 87.5%; p=0.441). A frequent angiographic finding regarding the failure of FAST was that the M2 occlusion was located immediately after severe acute angulation between M1 and M2. CONCLUSIONS: Stent retriever thrombectomy may provide faster reperfusion than FAST, while the FAST technique might be associated with lower distal embolization and a higher reperfusion rate for the first thrombectomy attempt, but without any significant difference in clinical outcome. When choosing the EVT method for M2 occlusions, consideration of the location of the occlusion and tortuosity between M1 and M2 might be helpful to achieve a better angiographic outcome. PMID- 27382125 TI - Treatment of complex anterior cerebral artery aneurysms with Pipeline flow diversion: mid-term results. AB - BACKGROUND: The off-label use of flow diverters in the treatment of distal aneurysms continues to be debated. OBJECTIVE: To report our multicenter experience in the treatment of complex anterior cerebral artery aneurysms with the Pipeline embolization device (PED). METHODS: The neurointerventional databases of the four participating institutions were retrospectively reviewed for aneurysms treated with PED between October 2011 and January of 2016. All patients treated for anterior cerebral artery aneurysms were included in the analysis. Clinical presentation, location, type, vessel size, procedural complications, clinical and imaging follow-up were included in the analysis. RESULTS: Twenty patients (13 female) with 20 aneurysms met the inclusion criteria in our study. Fifteen aneurysms were classified as saccular and five as fusiform (mean size 7.3 mm). Thirteen aneurysms were located in the anterior communicating region (ACOM or A1/2 junction), six were A2-pericallosal, and one was located in the A1 segment. Six patients had presented previously with subarachnoid hemorrhage and had their aneurysms initially clipped or coiled. There was one minor event (a small caudate infarct) and one major event (intraparenchymal hemorrhage). Sixteen of the 20 patients had angiographic follow-up (mean 10 months). Eleven aneurysms were completely occluded, one had residual neck, and four had residual aneurysm filling. CONCLUSIONS: The treatment of complex anterior cerebral artery aneurysms with the PED as an alternative for patients who are not good candidates for conventional methods is technically feasible and safe. Mid-term results are promising but larger series with long-term follow-up are required to assess its effectiveness. PMID- 27382127 TI - Expression of cadR Enhances its Specific Activity for Cd Detoxification and Accumulation in Arabidopsis. AB - Cadmium (Cd) is a transition metal that is highly toxic in biological systems. Anthropogenic emissions of Cd have increased biogeochemical cycling and the amount of Cd in the biosphere. Here we studied the utility of a bacterial Cd binding protein, CadR, for the remediation of Cd contamination. CadR was successfully targeted to chloroplasts using a constitutive Cauliflower mosaic virus (CaMV) 35S promoter or a shoot-specific Chl a/b-binding protein 2 gene (CAB2) promoter and an RbcS (small subunit of the Rubisco complex) transit peptide. Under short-term (2 d) exposure to Cd, the cadR transgenic plants showed up to a 2.9-fold Cd accumulation in roots compared with untransformed plants. Under medium term (7 d) exposure to Cd, the concentrations of Cd in leaves began to increase but there were no differences between the wild type and the cadR transgenic plants. Under long-term (16 d) exposure to Cd, the cadR transgenic plants accumulated greater amounts of Cd in leaves than the untransformed plants. Total Cd accumulation (ug per plant) in shoots and roots of the plants expressing cadR were significantly higher (up to 3.5-fold in shoots and 5.2-fold in roots) than those of the untransformed plants. We also found that targeting CadR to chloroplasts facilitated chloroplastic metal homeostasis and Chl b accumulation. Our results demonstrate that manipulating chelating capacity in chloroplasts or in the cytoplasm may be effective in modifying both the accumulation of and resistance to Cd. PMID- 27382126 TI - Organisational characteristics associated with shift work practices and potential opportunities for intervention: findings from a Canadian study. AB - INTRODUCTION: Shift work is a common working arrangement with wide-ranging implications for worker health. Organisational determinants of shift work practices are not well characterised; such information could be used to guide evidence-based research and best practices to mitigate shift work's negative effects. This exploratory study aimed to describe and assess organisational-level determinants of shift work practices thought to affect health, across a range of industry sectors. METHODS: Data on organisational characteristics, shift work scheduling, provision of shift work education materials/training to employees and night-time lighting policies in the workplace were collected during phone interviews with organisations across the Canadian province of British Columbia. Relationships between organisational characteristics and shift work practices were assessed using multivariable logistic regression models. RESULTS: The study sample included 88 participating organisations, representing 30 700 shift workers. Long-duration shifts, provision of shift work education materials/training to employees and night-time lighting policies were reported by approximately one-third of participating organisations. Odds of long-duration shifts increased in larger workplaces and by industry. Odds of providing shift work education materials/training increased in larger workplaces, in organisations reporting concern for shift worker health and in organisations without seasonal changes in shift work. Odds of night-time lighting policies in the workplace increased in organisations reporting previous workplace accidents or incidents that occurred during non-daytime hours, site maintenance needs and client service or care needs. CONCLUSIONS: This study points to organisational determinants of shift work practices that could be useful for targeting research and workplace interventions. Results should be interpreted as preliminary in an emerging body of literature on shift work and health. PMID- 27382128 TI - Characterization of the AtSPX3 Promoter Elucidates its Complex Regulation in Response to Phosphorus Deficiency. AB - AtSPX3, responding to phosphate (Pi) deficiency by its expression, is an important gene involved in Pi homeostasis in Arabidopsis. To understand its transcriptional regulation, we characterized the AtSPX3 promoter by distal truncation, internal deletion and mutation of the predicted cis-elements, and identified multiple cis-elements responsive to Pi status. The P1BS (AtPHR-binding site) and AtMyb4 (putative MYB4-binding site) elements were two main cis-elements in the AtSPX3 promoter. P1BS is essential and has a dosage effect for activating expression of the gene under Pi deficiency, while the element AtMyb4 possesses a dual function: one is to enhance AtSPX3 expression in roots under Pi deficiency, and the other one is to repress AtSPX3 expression in shoots under both Pi deficiency and sufficiency. Moreover, we confirmed that AtPHR1, a key transcription factor in Pi homeostasis of plants, was required for the negative regulation function of the AtMyb4 element in shoots. Additionally, we also found that the AtSPX3 promoter had a length limitation for activating gene expression. Generally, our findings in this work are useful for understanding the molecular regulation mechanism of genes involved in Pi uptake and homeostasis. PMID- 27382130 TI - Correction: Differential T Cell Cytokine Receptivity and Not Signal Quality Distinguishes IL-6 and IL-10 Signaling during Th17 Differentiation. PMID- 27382131 TI - Correction: Response to Comment on "Deficient NLRP3 and AIM2 Inflammasome Function in Autoimmune NZB Mice". PMID- 27382129 TI - The Latent Reservoir for HIV-1: How Immunologic Memory and Clonal Expansion Contribute to HIV-1 Persistence. AB - Combination antiretroviral therapy (ART) for HIV-1 infection reduces plasma virus levels to below the limit of detection of clinical assays. However, even with prolonged suppression of viral replication with ART, viremia rebounds rapidly after treatment interruption. Thus, ART is not curative. The principal barrier to cure is a remarkably stable reservoir of latent HIV-1 in resting memory CD4(+) T cells. In this review, we consider explanations for the remarkable stability of the latent reservoir. Stability does not appear to reflect replenishment from new infection events but rather normal physiologic processes that provide for immunologic memory. Of particular importance are proliferative processes that drive clonal expansion of infected cells. Recent evidence suggests that in some infected cells, proliferation is a consequence of proviral integration into host genes associated with cell growth. Efforts to cure HIV-1 infection by targeting the latent reservoir may need to consider the potential of latently infected cells to proliferate. PMID- 27382132 TI - Genome-Wide Analysis of Host Responses to Four Different Types of Microorganisms in Bombyx Mori (Lepidoptera: Bombycidae). AB - Several pathogenic microorganisms have been used to investigate the genome-wide transcriptional responses of Bombyx mori to infection. However, studies have so far each focused on one microorganism, and systematic genome-wide comparison of transcriptional responses to different pathogenic microorganisms has not been undertaken. Here, we surveyed transcriptional responses of B. mori to its natural bacterial, viral, and fungal pathogens, Bacillus bombyseptieus, B. mori nucleopolyhedrovirus (BmNPV), and Beauveria bassiana, respectively, and to nonpathogenic Escherichia coli, by microarray analysis. In total, the expression of 2,436, 1,804, 1,743, and 912 B. mori genes was modulated by infection with B. bombyseptieus, BmNPV, B. bassiana, and E. coli, respectively. Notably, the expression of 620, 400, 177, or 165 of these genes was only modulated by infection with B. bombyseptieus, BmNPV, B. bassiana, or E. coli, respectively. In contrast to the expression of genes related to juvenile hormone synthesis and metabolism, that of genes encoding juvenile hormone binding proteins was microorganism-specific. Three basal metabolic pathways were modulated by infection with any of the four microorganisms, and 3, 14, 5, and 2 metabolic pathways were specifically modulated by infection with B. bombyseptieus, BmNPV, B. bassiana, and E. coli, respectively. Interestingly, BmNPV infection modulated the JAK/STAT signaling pathway, whereas both the Imd and Toll signaling pathways were modulated by infection with B. bombyseptieus, B. bassiana, or E. coli These results elucidate potential molecular mechanisms of the host response to different microorganisms, and provide a foundation for further work on host pathogen interaction. PMID- 27382133 TI - Eavesdropping to Find Mates: The Function of Male Hearing for a Cicada-Hunting Parasitoid Fly, Emblemasoma erro (Diptera: Sarcophagidae). AB - Females of several species of dipteran parasitoids use long-range hearing to locate hosts for their offspring by eavesdropping on the acoustic mating calls of other insects. Males of these acoustic eavesdropping parasitoids also have physiologically functional ears, but so far, no adaptive function for male hearing has been discovered. I investigated the function of male hearing for the sarcophagid fly Emblemasoma erro Aldrich, an acoustic parasitoid of cicadas, by testing the hypothesis that both male and female E. erro use hearing to locate potential mates. I found that both male and nongravid female E. erro perform phonotaxis to the sounds of calling cicadas, that male flies engage in short range, mate-finding behavior once they arrive at a sound source, and that encounters between females and males at a sound source can lead to copulation. Thus, cicada calling songs appear to serve as a mate-finding cue for both sexes of E. erro Emblemasoma erro's mate-finding behavior is compared to that of other sarcophagid flies, other acoustic parasitoids, and nonacoustic eavesdropping parasitoids. PMID- 27382134 TI - Validation of the "Step-by-Step" Approach in the Management of Young Febrile Infants. AB - BACKGROUND: A sequential approach to young febrile infants on the basis of clinical and laboratory parameters, including procalcitonin, was recently described as an accurate tool in identifying patients at risk for invasive bacterial infection (IBI). Our aim was to prospectively validate the Step-by-Step approach and compare it with the Rochester criteria and the Lab-score. METHODS: Prospective study including infants <=90 days with fever without source presenting in 11 European pediatric emergency departments between September 2012 and August 2014. The accuracy of the Step-by-Step approach, the Rochester criteria, and the Lab-score in identifying patients at low risk of IBI (isolation of a bacterial pathogen in a blood or cerebrospinal fluid culture) was compared. RESULTS: Eighty-seven of 2185 infants (4.0%) were diagnosed with an IBI. The prevalence of IBI was significantly higher in infants classified as high risk or intermediate risk according to the Step by Step than in low risk patients. Sensitivity and negative predictive value for ruling out an IBI were 92.0% and 99.3% for the Step by Step, 81.6% and 98.3% for the Rochester criteria, and 59.8% and 98.1% for the Lab-score. Seven infants with an IBI were misclassified by the Step by Step, 16 by Rochester criteria, and 35 by the Lab-score. CONCLUSIONS: We validated the Step by Step as a valuable tool for the management of infants with fever without source in the emergency department and confirmed its superior accuracy in identifying patients at low risk of IBI, compared with the Rochester criteria and the Lab-score. PMID- 27382135 TI - Should We Evaluate Febrile Young Infants Step-by-Step in the Emergency Department? PMID- 27382136 TI - Marketing Vegetables in Elementary School Cafeterias to Increase Uptake. AB - OBJECTIVES: Children do not eat enough servings of vegetables, underscoring the need for effective interventions encouraging this behavior. The purpose of this research was to measure the impact that daily exposure to branded vegetable characters has on vegetable selection among boys and girls in elementary schools. METHODS: In a large urban school district, 10 elementary schools agreed to participate in the study. They were randomly assigned to a control condition or 1 of 3 treatment conditions: (1) a vinyl banner displaying vegetable characters that was fastened around the base of the salad bar; (2) short television segments with health education delivered by vegetable characters; or (3) a combination of the vinyl banner and television segments. We collected 22 206 student-day observations over a 6-week period by tallying the number of boys and girls taking vegetables from the school's salad bar. RESULTS: Results show that 90.5% (from 12.6% to 24.0%; P = .04) more students took vegetables from the salad bar when exposed to the vinyl banner only, and 239.2% (from 10.2% to 34.6%; P < .001) more students visited the salad bar when exposed to both the television segments and vinyl banners. Both boys and girls responded positively to the vinyl banners (P < .05 in both cases). CONCLUSIONS: Evidence from this study highlights the positive impact of branded media on children's vegetable selection in the school cafeteria. Results from this study suggest potential opportunities for using branded media to encourage healthier choices for children. PMID- 27382137 TI - Overexpression of the OsERF71 Transcription Factor Alters Rice Root Structure and Drought Resistance. AB - Plant responses to drought stress require the regulation of transcriptional networks via drought-responsive transcription factors, which mediate a range of morphological and physiological changes. AP2/ERF transcription factors are known to act as key regulators of drought resistance transcriptional networks; however, little is known about the associated molecular mechanisms that give rise to specific morphological and physiological adaptations. In this study, we functionally characterized the rice (Oryza sativa) drought-responsive AP2/ERF transcription factor OsERF71, which is expressed predominantly in the root meristem, pericycle, and endodermis. Overexpression of OsERF71, either throughout the entire plant or specifically in roots, resulted in a drought resistance phenotype at the vegetative growth stage, indicating that overexpression in roots was sufficient to confer drought resistance. The root-specific overexpression was more effective in conferring drought resistance at the reproductive stage, such that grain yield was increased by 23% to 42% over wild-type plants or whole-body overexpressing transgenic lines under drought conditions. OsERF71 overexpression in roots elevated the expression levels of genes related to cell wall loosening and lignin biosynthetic genes, which correlated with changes in root structure, the formation of enlarged aerenchyma, and high lignification levels. Furthermore, OsERF71 was found to directly bind to the promoter of OsCINNAMOYL-COENZYME A REDUCTASE1, a key gene in lignin biosynthesis. These results indicate that the OsERF71-mediated drought resistance pathway recruits factors involved in cell wall modification to enable root morphological adaptations, thereby providing a mechanism for enhancing drought resistance. PMID- 27382141 TI - Opinion: In the wake of Paris Agreement, scientists must embrace new directions for climate change research. PMID- 27382139 TI - Evolutionary Co-Option of Floral Meristem Identity Genes for Patterning of the Flower-Like Asteraceae Inflorescence. AB - The evolutionary success of Asteraceae, the largest family of flowering plants, has been attributed to the unique inflorescence architecture of the family, which superficially resembles an individual flower. Here, we show that Asteraceae inflorescences (flower heads, or capitula) resemble solitary flowers not only morphologically but also at the molecular level. By conducting functional analyses for orthologs of the flower meristem identity genes LEAFY (LFY) and UNUSUAL FLORAL ORGANS (UFO) in Gerbera hybrida, we show that GhUFO is the master regulator of flower meristem identity, while GhLFY has evolved a novel, homeotic function during the evolution of head-like inflorescences. Resembling LFY expression in a single flower meristem, uniform expression of GhLFY in the inflorescence meristem defines the capitulum as a determinate structure that can assume floral fate upon ectopic GhUFO expression. We also show that GhLFY uniquely regulates the ontogeny of outer, expanded ray flowers but not inner, compact disc flowers, indicating that the distinction of different flower types in Asteraceae is connected with their independent evolutionary origins from separate branching systems. PMID- 27382143 TI - Drawing causal inference from Big Data. PMID- 27382138 TI - Suppressing Farnesyl Diphosphate Synthase Alters Chloroplast Development and Triggers Sterol-Dependent Induction of Jasmonate- and Fe-Related Responses. AB - Farnesyl diphosphate synthase (FPS) catalyzes the synthesis of farnesyl diphosphate from isopentenyl diphosphate and dimethylallyl diphosphate. Arabidopsis (Arabidopsis thaliana) contains two genes (FPS1 and FPS2) encoding FPS. Single fps1 and fps2 knockout mutants are phenotypically indistinguishable from wild-type plants, while fps1/fps2 double mutants are embryo lethal. To assess the effect of FPS down-regulation at postembryonic developmental stages, we generated Arabidopsis conditional knockdown mutants expressing artificial microRNAs devised to simultaneously silence both FPS genes. Induction of silencing from germination rapidly caused chlorosis and a strong developmental phenotype that led to seedling lethality. However, silencing of FPS after seed germination resulted in a slight developmental delay only, although leaves and cotyledons continued to show chlorosis and altered chloroplasts. Metabolomic analyses also revealed drastic changes in the profile of sterols, ubiquinones, and plastidial isoprenoids. RNA sequencing and reverse transcription-quantitative polymerase chain reaction transcriptomic analysis showed that a reduction in FPS activity levels triggers the misregulation of genes involved in biotic and abiotic stress responses, the most prominent one being the rapid induction of a set of genes related to the jasmonic acid pathway. Down-regulation of FPS also triggered an iron-deficiency transcriptional response that is consistent with the iron-deficient phenotype observed in FPS-silenced plants. The specific inhibition of the sterol biosynthesis pathway by chemical and genetic blockage mimicked these transcriptional responses, indicating that sterol depletion is the primary cause of the observed alterations. Our results highlight the importance of sterol homeostasis for normal chloroplast development and function and reveal important clues about how isoprenoid and sterol metabolism is integrated within plant physiology and development. PMID- 27382144 TI - Causal inference in economics and marketing. AB - This is an elementary introduction to causal inference in economics written for readers familiar with machine learning methods. The critical step in any causal analysis is estimating the counterfactual-a prediction of what would have happened in the absence of the treatment. The powerful techniques used in machine learning may be useful for developing better estimates of the counterfactual, potentially improving causal inference. PMID- 27382145 TI - Estimating peer effects in networks with peer encouragement designs. AB - Peer effects, in which the behavior of an individual is affected by the behavior of their peers, are central to social science. Because peer effects are often confounded with homophily and common external causes, recent work has used randomized experiments to estimate effects of specific peer behaviors. These experiments have often relied on the experimenter being able to randomly modulate mechanisms by which peer behavior is transmitted to a focal individual. We describe experimental designs that instead randomly assign individuals' peers to encouragements to behaviors that directly affect those individuals. We illustrate this method with a large peer encouragement design on Facebook for estimating the effects of receiving feedback from peers on posts shared by focal individuals. We find evidence for substantial effects of receiving marginal feedback on multiple behaviors, including giving feedback to others and continued posting. These findings provide experimental evidence for the role of behaviors directed at specific individuals in the adoption and continued use of communication technologies. In comparison, observational estimates differ substantially, both underestimating and overestimating effects, suggesting that researchers and policy makers should be cautious in relying on them. PMID- 27382146 TI - Quantity discounts on a virtual good: The results of a massive pricing experiment at King Digital Entertainment. AB - We report on a natural field experiment on quantity discounts involving more than 14 million consumers. Implementing price reductions ranging from 9-70% for large purchases, we found remarkably little impact on revenue, either positively or negatively. There was virtually no increase in the quantity of customers making a purchase; all the observed changes occurred for customers who already were buyers. We found evidence that infrequent purchasers are more responsive to discounts than frequent purchasers. There was some evidence of habit formation when prices returned to pre-experiment levels. There also was some evidence that consumers contemplating small purchases are discouraged by the presence of extreme quantity discounts for large purchases. PMID- 27382148 TI - Causal inference and the data-fusion problem. AB - We review concepts, principles, and tools that unify current approaches to causal analysis and attend to new challenges presented by big data. In particular, we address the problem of data fusion-piecing together multiple datasets collected under heterogeneous conditions (i.e., different populations, regimes, and sampling methods) to obtain valid answers to queries of interest. The availability of multiple heterogeneous datasets presents new opportunities to big data analysts, because the knowledge that can be acquired from combined data would not be possible from any individual source alone. However, the biases that emerge in heterogeneous environments require new analytical tools. Some of these biases, including confounding, sampling selection, and cross-population biases, have been addressed in isolation, largely in restricted parametric models. We here present a general, nonparametric framework for handling these biases and, ultimately, a theoretical solution to the problem of data fusion in causal inference tasks. PMID- 27382149 TI - Recursive partitioning for heterogeneous causal effects. AB - In this paper we propose methods for estimating heterogeneity in causal effects in experimental and observational studies and for conducting hypothesis tests about the magnitude of differences in treatment effects across subsets of the population. We provide a data-driven approach to partition the data into subpopulations that differ in the magnitude of their treatment effects. The approach enables the construction of valid confidence intervals for treatment effects, even with many covariates relative to the sample size, and without "sparsity" assumptions. We propose an "honest" approach to estimation, whereby one sample is used to construct the partition and another to estimate treatment effects for each subpopulation. Our approach builds on regression tree methods, modified to optimize for goodness of fit in treatment effects and to account for honest estimation. Our model selection criterion anticipates that bias will be eliminated by honest estimation and also accounts for the effect of making additional splits on the variance of treatment effect estimates within each subpopulation. We address the challenge that the "ground truth" for a causal effect is not observed for any individual unit, so that standard approaches to cross-validation must be modified. Through a simulation study, we show that for our preferred method honest estimation results in nominal coverage for 90% confidence intervals, whereas coverage ranges between 74% and 84% for nonhonest approaches. Honest estimation requires estimating the model with a smaller sample size; the cost in terms of mean squared error of treatment effects for our preferred method ranges between 7-22%. PMID- 27382150 TI - Methods for causal inference from gene perturbation experiments and validation. AB - Inferring causal effects from observational and interventional data is a highly desirable but ambitious goal. Many of the computational and statistical methods are plagued by fundamental identifiability issues, instability, and unreliable performance, especially for large-scale systems with many measured variables. We present software and provide some validation of a recently developed methodology based on an invariance principle, called invariant causal prediction (ICP). The ICP method quantifies confidence probabilities for inferring causal structures and thus leads to more reliable and confirmatory statements for causal relations and predictions of external intervention effects. We validate the ICP method and some other procedures using large-scale genome-wide gene perturbation experiments in Saccharomyces cerevisiae The results suggest that prediction and prioritization of future experimental interventions, such as gene deletions, can be improved by using our statistical inference techniques. PMID- 27382147 TI - Inferring cortical function in the mouse visual system through large-scale systems neuroscience. AB - The scientific mission of the Project MindScope is to understand neocortex, the part of the mammalian brain that gives rise to perception, memory, intelligence, and consciousness. We seek to quantitatively evaluate the hypothesis that neocortex is a relatively homogeneous tissue, with smaller functional modules that perform a common computational function replicated across regions. We here focus on the mouse as a mammalian model organism with genetics, physiology, and behavior that can be readily studied and manipulated in the laboratory. We seek to describe the operation of cortical circuitry at the computational level by comprehensively cataloging and characterizing its cellular building blocks along with their dynamics and their cell type-specific connectivities. The project is also building large-scale experimental platforms (i.e., brain observatories) to record the activity of large populations of cortical neurons in behaving mice subject to visual stimuli. A primary goal is to understand the series of operations from visual input in the retina to behavior by observing and modeling the physical transformations of signals in the corticothalamic system. We here focus on the contribution that computer modeling and theory make to this long term effort. PMID- 27382151 TI - Improving massive experiments with threshold blocking. AB - Inferences from randomized experiments can be improved by blocking: assigning treatment in fixed proportions within groups of similar units. However, the use of the method is limited by the difficulty in deriving these groups. Current blocking methods are restricted to special cases or run in exponential time; are not sensitive to clustering of data points; and are often heuristic, providing an unsatisfactory solution in many common instances. We present an algorithm that implements a widely applicable class of blocking-threshold blocking-that solves these problems. Given a minimum required group size and a distance metric, we study the blocking problem of minimizing the maximum distance between any two units within the same group. We prove this is a nondeterministic polynomial-time hard problem and derive an approximation algorithm that yields a blocking where the maximum distance is guaranteed to be, at most, four times the optimal value. This algorithm runs in O(n log n) time with O(n) space complexity. This makes it, to our knowledge, the first blocking method with an ensured level of performance that works in massive experiments. Whereas many commonly used algorithms form pairs of units, our algorithm constructs the groups flexibly for any chosen minimum size. This facilitates complex experiments with several treatment arms and clustered data. A simulation study demonstrates the efficiency and efficacy of the algorithm; tens of millions of units can be blocked using a desktop computer in a few minutes. PMID- 27382152 TI - Linear mixed model for heritability estimation that explicitly addresses environmental variation. AB - The linear mixed model (LMM) is now routinely used to estimate heritability. Unfortunately, as we demonstrate, LMM estimates of heritability can be inflated when using a standard model. To help reduce this inflation, we used a more general LMM with two random effects-one based on genomic variants and one based on easily measured spatial location as a proxy for environmental effects. We investigated this approach with simulated data and with data from a Uganda cohort of 4,778 individuals for 34 phenotypes including anthropometric indices, blood factors, glycemic control, blood pressure, lipid tests, and liver function tests. For the genomic random effect, we used identity-by-descent estimates from accurately phased genome-wide data. For the environmental random effect, we constructed a covariance matrix based on a Gaussian radial basis function. Across the simulated and Ugandan data, narrow-sense heritability estimates were lower using the more general model. Thus, our approach addresses, in part, the issue of "missing heritability" in the sense that much of the heritability previously thought to be missing was fictional. Software is available at https://github.com/MicrosoftGenomics/FaST-LMM. PMID- 27382153 TI - Lasso adjustments of treatment effect estimates in randomized experiments. AB - We provide a principled way for investigators to analyze randomized experiments when the number of covariates is large. Investigators often use linear multivariate regression to analyze randomized experiments instead of simply reporting the difference of means between treatment and control groups. Their aim is to reduce the variance of the estimated treatment effect by adjusting for covariates. If there are a large number of covariates relative to the number of observations, regression may perform poorly because of overfitting. In such cases, the least absolute shrinkage and selection operator (Lasso) may be helpful. We study the resulting Lasso-based treatment effect estimator under the Neyman-Rubin model of randomized experiments. We present theoretical conditions that guarantee that the estimator is more efficient than the simple difference-of means estimator, and we provide a conservative estimator of the asymptotic variance, which can yield tighter confidence intervals than the difference-of means estimator. Simulation and data examples show that Lasso-based adjustment can be advantageous even when the number of covariates is less than the number of observations. Specifically, a variant using Lasso for selection and ordinary least squares (OLS) for estimation performs particularly well, and it chooses a smoothing parameter based on combined performance of Lasso and OLS. PMID- 27382154 TI - Modeling confounding by half-sibling regression. AB - We describe a method for removing the effect of confounders to reconstruct a latent quantity of interest. The method, referred to as "half-sibling regression," is inspired by recent work in causal inference using additive noise models. We provide a theoretical justification, discussing both independent and identically distributed as well as time series data, respectively, and illustrate the potential of the method in a challenging astronomy application. PMID- 27382156 TI - Quantifying the origins of life on a planetary scale. AB - A simple, heuristic formula with parallels to the Drake Equation is introduced to help focus discussion on open questions for the origins of life in a planetary context. This approach indicates a number of areas where quantitative progress can be made on parameter estimation for determining origins of life probabilities, based on constraints from Bayesian approaches. We discuss a variety of "microscale" factors and their role in determining "macroscale" abiogenesis probabilities on suitable planets. We also propose that impact ejecta exchange between planets with parallel chemistries and chemical evolution could in principle amplify the development of molecular complexity and abiogenesis probabilities. This amplification could be very significant, and both bias our conclusions about abiogenesis probabilities based on the Earth and provide a major source of variance in the probability of life arising in planetary systems. We use our heuristic formula to suggest a number of observational routes for improving constraints on origins of life probabilities. PMID- 27382155 TI - Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose. AB - Vaccines have had broad medical impact, but existing vaccine technologies and production methods are limited in their ability to respond rapidly to evolving and emerging pathogens, or sudden outbreaks. Here, we develop a rapid-response, fully synthetic, single-dose, adjuvant-free dendrimer nanoparticle vaccine platform wherein antigens are encoded by encapsulated mRNA replicons. To our knowledge, this system is the first capable of generating protective immunity against a broad spectrum of lethal pathogen challenges, including H1N1 influenza, Toxoplasma gondii, and Ebola virus. The vaccine can be formed with multiple antigen-expressing replicons, and is capable of eliciting both CD8(+) T-cell and antibody responses. The ability to generate viable, contaminant-free vaccines within days, to single or multiple antigens, may have broad utility for a range of diseases. PMID- 27382157 TI - Nematic quantum critical point without magnetism in FeSe1-xSx superconductors. AB - In most unconventional superconductors, the importance of antiferromagnetic fluctuations is widely acknowledged. In addition, cuprate and iron-pnictide high temperature superconductors often exhibit unidirectional (nematic) electronic correlations, including stripe and orbital orders, whose fluctuations may also play a key role for electron pairing. In these materials, however, such nematic correlations are intertwined with antiferromagnetic or charge orders, preventing the identification of the essential role of nematic fluctuations. This calls for new materials having only nematicity without competing or coexisting orders. Here we report systematic elastoresistance measurements in FeSe1-xSx superconductors, which, unlike other iron-based families, exhibit an electronic nematic order without accompanying antiferromagnetic order. We find that the nematic transition temperature decreases with sulfur content x; whereas, the nematic fluctuations are strongly enhanced. Near [Formula: see text], the nematic susceptibility diverges toward absolute zero, revealing a nematic quantum critical point. The obtained phase diagram for the nematic and superconducting states highlights FeSe1-xSx as a unique nonmagnetic system suitable for studying the impact of nematicity on superconductivity. PMID- 27382158 TI - Cardiolipin binds selectively but transiently to conserved lysine residues in the rotor of metazoan ATP synthases. AB - The anionic lipid cardiolipin is an essential component of active ATP synthases. In metazoans, their rotors contain a ring of eight c-subunits consisting of inner and outer circles of N- and C-terminal alpha-helices, respectively. The beginning of the C-terminal alpha-helix contains a strictly conserved and fully trimethylated lysine residue in the lipid head-group region of the membrane. Larger rings of known structure, from c9-c15 in eubacteria and chloroplasts, conserve either a lysine or an arginine residue in the equivalent position. In computer simulations of hydrated membranes containing trimethylated or unmethylated bovine c8-rings and bacterial c10- or c11-rings, the head-groups of cardiolipin molecules became associated selectively with these modified and unmodified lysine residues and with adjacent polar amino acids and with a second conserved lysine on the opposite side of the membrane, whereas phosphatidyl lipids were attracted little to these sites. However, the residence times of cardiolipin molecules with the ring were brief and sufficient for the rotor to turn only a fraction of a degree in the active enzyme. With the demethylated c8 ring and with c10- and c11-rings, the density of bound cardiolipin molecules at this site increased, but residence times were not changed greatly. These highly specific but brief interactions with the rotating c-ring are consistent with functional roles for cardiolipin in stabilizing and lubricating the rotor, and, by interacting with the enzyme at the inlet and exit of the transmembrane proton channel, in participation in proton translocation through the membrane domain of the enzyme. PMID- 27382159 TI - Cook Island artifact geochemistry demonstrates spatial and temporal extent of pre European interarchipelago voyaging in East Polynesia. AB - The Cook Islands are considered the "gateway" for human colonization of East Polynesia, the final chapter of Oceanic settlement and the last major region occupied on Earth. Indeed, East Polynesia witnessed the culmination of the greatest maritime migration in human history. Perennial debates have critiqued whether Oceanic settlement was purposeful or accidental, the timing and pathways of colonization, and the nature and extent of postcolonization voyaging-essential for small founding groups securing a lifeline between parent and daughter communities. Centering on the well-dated Tangatatau rockshelter, Mangaia, Southern Cook Islands, we charted the temporal duration and geographic spread of exotic stone adze materials-essential woodworking tools found throughout Polynesia- imported for more than 300 y beginning in the early AD 1300s. Using a technique requiring only 200 mg of sample for the geochemical analysis of trace elements and isotopes of fine-grained basalt adzes, we assigned all artifacts to an island or archipelago of origin. Adze material was identified from the chiefly complex on the Austral Islands, from the major adze quarry complex on Tutuila (Samoa), and from the Marquesas Islands more than 2,400 km distant. This interaction is the only dated example of down-the-line exchange in central East Polynesia where intermediate groups transferred commodities attesting to the interconnectedness and complexity of social relations fostered during postsettlement voyaging. For the Cook Islands, this exchange may have lasted into the 1600s, at least a century later than other East Polynesian archipelagos, suggesting that interarchipelago interaction contributed to the later development of social hierarchies. PMID- 27382161 TI - Blood sugar level follows perceived time rather than actual time in people with type 2 diabetes. AB - The current study investigates whether perceived time has an effect on blood glucose level in people with type 2 diabetes. The hypothesis is that perceived time will have a greater influence over blood glucose level than actual time. Changes in blood glucose levels were measured in 46 participants with diabetes while they completed simple tasks during a 90-min period. Participants' perception of time was manipulated by having them refer to clocks that were either accurate or altered to run fast or slow. Blood glucose levels changed in accordance with how much time they believed had passed instead of how much time had actually passed. These results are an example of the influence psychological processes can directly exert on the body. PMID- 27382160 TI - Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801 triggered lung protein modification and proteolysis. AB - Cigarette smoking causes emphysema, a fatal disease involving extensive structural and functional damage of the lung. Using a guinea pig model and human lung cells, we show that oxidant(s) present in tobacco smoke not only cause direct oxidative damage of lung proteins, contributing to the major share of lung injury, but also activate Rtp801, a key proinflammatory cellular factor involved in tobacco smoke-induced lung damage. Rtp801 triggers nuclear factor kappaB and consequent inducible NOS (iNOS)-mediated overproduction of NO, which in combination with excess superoxide produced during Rtp801 activation, contribute to increased oxido-nitrosative stress and lung protein nitration. However, lung specific inhibition of iNOS with a iNOS-specific inhibitor, N6-(1-iminoethyl)-L lysine, dihydrochloride (L-NIL) solely restricts lung protein nitration but fails to prevent or reverse the major tobacco smoke-induced oxidative lung injury. In comparison, the dietary antioxidant, ascorbate or vitamin C, can substantially prevent such damage by inhibiting both tobacco smoke-induced lung protein oxidation as well as activation of pulmonary Rtp801 and consequent iNOS/NO induced nitration of lung proteins, that otherwise lead to increased proteolysis of such oxidized or nitrated proteins by endogenous lung proteases, resulting in emphysematous lung damage. Vitamin C also restricts the up-regulation of matrix metalloproteinase-9, the major lung protease involved in the proteolysis of such modified lung proteins during tobacco smoke-induced emphysema. Overall, our findings implicate tobacco-smoke oxidant(s) as the primary etiopathogenic factor behind both the noncellular and cellular damage mechanisms governing emphysematous lung injury and demonstrate the potential of vitamin C to accomplish holistic prevention of such damage. PMID- 27382162 TI - Cytosine deamination and the precipitous decline of spontaneous mutation during Earth's history. AB - The hydrolytic deamination of cytosine and 5-methylcytosine residues in DNA appears to contribute significantly to the appearance of spontaneous mutations in microorganisms and in human disease. In the present work, we examined the mechanism of cytosine deamination and the response of the uncatalyzed reaction to changing temperature. The positively charged 1,3-dimethylcytosinium ion was hydrolyzed at a rate similar to the rate of acid-catalyzed hydrolysis of 1 methylcytosine, for which it furnishes a satisfactory kinetic model and a probable mechanism. In agreement with earlier reports, uncatalyzed deamination was found to proceed at very similar rates for cytosine, 1-methylcytosine, cytidine, and cytidine 5'-phosphate, and also for cytosine residues in single stranded DNA generated from a phagemid, in which we sequenced an insert representing the gene of the HIV-1 protease. Arrhenius plots for the uncatalyzed deamination of cytosine were linear over the temperature range from 90 degrees C to 200 degrees C and indicated a heat of activation (DeltaH(?)) of 23.4 +/- 0.5 kcal/mol at pH 7. Recent evidence indicates that the surface of the earth has been cool enough to support life for more than 4 billion years and that life has been present for almost as long. If the temperature at Earth's surface is assumed to have followed Newton's law of cooling, declining exponentially from 100 degrees C to 25 degrees C during that period, then half of the cytosine deaminating events per unit biomass would have taken place during the first 0.2 billion years, and <99.4% would have occurred during the first 2 billion years. PMID- 27382163 TI - Large scale, synchronous variability of marine fish populations driven by commercial exploitation. AB - Synchronous variations in the abundance of geographically distinct marine fish populations are known to occur across spatial scales on the order of 1,000 km and greater. The prevailing assumption is that this large-scale coherent variability is a response to coupled atmosphere-ocean dynamics, commonly represented by climate indexes, such as the Atlantic Multidecadal Oscillation and North Atlantic Oscillation. On the other hand, it has been suggested that exploitation might contribute to this coherent variability. This possibility has been generally ignored or dismissed on the grounds that exploitation is unlikely to operate synchronously at such large spatial scales. Our analysis of adult fishing mortality and spawning stock biomass of 22 North Atlantic cod (Gadus morhua) stocks revealed that both the temporal and spatial scales in fishing mortality and spawning stock biomass were equivalent to those of the climate drivers. From these results, we conclude that greater consideration must be given to the potential of exploitation as a driving force behind broad, coherent variability of heavily exploited fish species. PMID- 27382165 TI - Correction for Chappell and Rausher, Evolution of host range in Coleosporium ipomoeae, a plant pathogen with multiple hosts. PMID- 27382164 TI - Learning rational temporal eye movement strategies. AB - During active behavior humans redirect their gaze several times every second within the visual environment. Where we look within static images is highly efficient, as quantified by computational models of human gaze shifts in visual search and face recognition tasks. However, when we shift gaze is mostly unknown despite its fundamental importance for survival in a dynamic world. It has been suggested that during naturalistic visuomotor behavior gaze deployment is coordinated with task-relevant events, often predictive of future events, and studies in sportsmen suggest that timing of eye movements is learned. Here we establish that humans efficiently learn to adjust the timing of eye movements in response to environmental regularities when monitoring locations in the visual scene to detect probabilistically occurring events. To detect the events humans adopt strategies that can be understood through a computational model that includes perceptual and acting uncertainties, a minimal processing time, and, crucially, the intrinsic costs of gaze behavior. Thus, subjects traded off event detection rate with behavioral costs of carrying out eye movements. Remarkably, based on this rational bounded actor model the time course of learning the gaze strategies is fully explained by an optimal Bayesian learner with humans' characteristic uncertainty in time estimation, the well-known scalar law of biological timing. Taken together, these findings establish that the human visual system is highly efficient in learning temporal regularities in the environment and that it can use these regularities to control the timing of eye movements to detect behaviorally relevant events. PMID- 27382166 TI - Profile of Martin Matzuk. PMID- 27382167 TI - Polymorphism and electronic structure of polyimine and its potential significance for prebiotic chemistry on Titan. AB - The chemistry of hydrogen cyanide (HCN) is believed to be central to the origin of life question. Contradictions between Cassini-Huygens mission measurements of the atmosphere and the surface of Saturn's moon Titan suggest that HCN-based polymers may have formed on the surface from products of atmospheric chemistry. This makes Titan a valuable "natural laboratory" for exploring potential nonterrestrial forms of prebiotic chemistry. We have used theoretical calculations to investigate the chain conformations of polyimine (pI), a polymer identified as one major component of polymerized HCN in laboratory experiments. Thanks to its flexible backbone, the polymer can exist in several different polymorphs, which are relatively close in energy. The electronic and structural variability among them is extraordinary. The band gap changes over a 3-eV range when moving from a planar sheet-like structure to increasingly coiled conformations. The primary photon absorption is predicted to occur in a window of relative transparency in Titan's atmosphere, indicating that pI could be photochemically active and drive chemistry on the surface. The thermodynamics for adding and removing HCN from pI under Titan conditions suggests that such dynamics is plausible, provided that catalysis or photochemistry is available to sufficiently lower reaction barriers. We speculate that the directionality of pI's intermolecular and intramolecular =N-H(...)N hydrogen bonds may drive the formation of partially ordered structures, some of which may synergize with photon absorption and act catalytically. Future detailed studies on proposed mechanisms and the solubility and density of the polymers will aid in the design of future missions to Titan. PMID- 27382169 TI - Measurements of extinct fission products in nuclear bomb debris: Determination of the yield of the Trinity nuclear test 70 y later. AB - This paper describes an approach to measuring extinct fission products that would allow for the characterization of a nuclear test at any time. The isotopic composition of molybdenum in five samples of glassy debris from the 1945 Trinity nuclear test has been measured. Nonnatural molybdenum isotopic compositions were observed, reflecting an input from the decay of the short-lived fission products (95)Zr and (97)Zr. By measuring both the perturbation of the (95)Mo/(96)Mo and (97)Mo/(96)Mo isotopic ratios and the total amount of molybdenum in the Trinity nuclear debris samples, it is possible to calculate the original concentrations of the (95)Zr and (97)Zr isotopes formed in the nuclear detonation. Together with a determination of the amount of plutonium in the debris, these measurements of extinct fission products allow for new estimates of the efficiency and yield of the historic Trinity test. PMID- 27382168 TI - pH-degradable imidazoquinoline-ligated nanogels for lymph node-focused immune activation. AB - Agonists of Toll-like receptors (TLRs) are potent activators of the innate immune system and hold promise as vaccine adjuvant and for anticancer immunotherapy. Unfortunately, in soluble form they readily enter systemic circulation and cause systemic inflammatory toxicity. Here we demonstrate that by covalent ligation of a small-molecule imidazoquinoline-based TLR7/8 agonist to 50-nm-sized degradable polymeric nanogels the potency of the agonist to activate TLR7/8 in in vitro cultured dendritic cells is largely retained. Importantly, imidazoquinoline ligated nanogels focused the in vivo immune activation on the draining lymph nodes while dramatically reducing systemic inflammation. Mechanistic studies revealed a prevalent passive diffusion of the nanogels to the draining lymph node. Moreover, immunization studies in mice have shown that relative to soluble TLR7/8 agonist, imidazoquinoline-ligated nanogels induce superior antibody and T cell responses against a tuberculosis antigen. This approach opens possibilities to enhance the therapeutic benefit of small-molecule TLR agonist for a variety of applications. PMID- 27382170 TI - Spontaneous wettability patterning via creasing instability. AB - Surfaces with patterned wettability contrast are important in industrial applications such as heat transfer, water collection, and particle separation. Traditional methods of fabricating such surfaces rely on microfabrication technologies, which are only applicable to certain substrates and are difficult to scale up and implement on curved surfaces. By taking advantage of a mechanical instability on a polyurethane elastomer film, we show that wettability patterns on both flat and curved surfaces can be generated spontaneously via a simple dip coating process. Variations in dipping time, sample prestress, and chemical treatment enable independent control of domain size (from about 100 to 500 MUm), morphology, and wettability contrast, respectively. We characterize the wettability contrast using local surface energy measurements via the sessile droplet technique and tensiometry. PMID- 27382171 TI - Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a heterogeneous, prevalent, chronic autoimmune disease characterized by painful swollen joints and significant disabilities. Symptomatic relief can be achieved in up to 50% of patients using biological agents that inhibit tumor necrosis factor (TNF) or other mechanisms of action, but there are no universally effective therapies. Recent advances in basic and preclinical science reveal that reflex neural circuits inhibit the production of cytokines and inflammation in animal models. One well-characterized cytokine inhibiting mechanism, termed the "inflammatory reflex," is dependent upon vagus nerve signals that inhibit cytokine production and attenuate experimental arthritis severity in mice and rats. It previously was unknown whether directly stimulating the inflammatory reflex in humans inhibits TNF production. Here we show that an implantable vagus nerve-stimulating device in epilepsy patients inhibits peripheral blood production of TNF, IL-1beta, and IL-6. Vagus nerve stimulation (up to four times daily) in RA patients significantly inhibited TNF production for up to 84 d. Moreover, RA disease severity, as measured by standardized clinical composite scores, improved significantly. Together, these results establish that vagus nerve stimulation targeting the inflammatory reflex modulates TNF production and reduces inflammation in humans. These findings suggest that it is possible to use mechanism-based neuromodulating devices in the experimental therapy of RA and possibly other autoimmune and autoinflammatory diseases. PMID- 27382172 TI - A study of interstellar aldehydes and enols as tracers of a cosmic ray-driven nonequilibrium synthesis of complex organic molecules. AB - Complex organic molecules such as sugars and amides are ubiquitous in star- and planet-forming regions, but their formation mechanisms have remained largely elusive until now. Here we show in a combined experimental, computational, and astrochemical modeling study that interstellar aldehydes and enols like acetaldehyde (CH3CHO) and vinyl alcohol (C2H3OH) act as key tracers of a cosmic ray-driven nonequilibrium chemistry leading to complex organics even deep within low-temperature interstellar ices at 10 K. Our findings challenge conventional wisdom and define a hitherto poorly characterized reaction class forming complex organic molecules inside interstellar ices before their sublimation in star forming regions such as SgrB2(N). These processes are of vital importance in initiating a chain of chemical reactions leading eventually to the molecular precursors of biorelevant molecules as planets form in their interstellar nurseries. PMID- 27382174 TI - Profile of Martin Pollak. PMID- 27382173 TI - Generalized nucleation and looping model for epigenetic memory of histone modifications. AB - Histone modifications can redistribute along the genome in a sequence-independent manner, giving rise to chromatin position effects and epigenetic memory. The underlying mechanisms shape the endogenous chromatin landscape and determine its response to ectopically targeted histone modifiers. Here, we simulate linear and looping-driven spreading of histone modifications and compare both models to recent experiments on histone methylation in fission yeast. We find that a generalized nucleation-and-looping mechanism describes key observations on engineered and endogenous methylation domains including intrinsic spatial confinement, independent regulation of domain size and memory, variegation in the absence of antagonists, and coexistence of short- and long-term memory at loci with weak and strong constitutive nucleation. These findings support a straightforward relationship between the biochemical properties of chromatin modifiers and the spatiotemporal modification pattern. The proposed mechanism gives rise to a phase diagram for cellular memory that may be generally applicable to explain epigenetic phenomena across different species. PMID- 27382175 TI - Insulin induction of SREBP-1c in rodent liver requires LXRalpha-C/EBPbeta complex. AB - Insulin increases lipid synthesis in liver by activating transcription of the gene encoding sterol regulatory element-binding protein-1c (SREBP-1c). SREBP-1c activates the transcription of all genes necessary for fatty acid synthesis. Insulin induction of SREBP-1c requires LXRalpha, a nuclear receptor. Transcription of SREBP-1c also requires transcription factor C/EBPbeta, but a connection between LXRalpha and C/EBPbeta has not been made. Here we show that LXRalpha and C/EBPbeta form a complex that can be immunoprecipitated from rat liver nuclei. Chromatin immunoprecipitation assays showed that the LXRalpha C/EBPbeta complex binds to the SREBP-1c promoter in a region that contains two binding sites for LXRalpha and is known to be required for insulin induction. Knockdown of C/EBPbeta in fresh rat hepatocytes or mouse livers in vivo reduces the ability of insulin to increase SREBP-1c mRNA. The LXRalpha-C/EBPbeta complex is bound to the SREBP-1c promoter in the absence or presence of insulin, indicating that insulin acts not by increasing the formation of this complex, but rather by activating it. PMID- 27382176 TI - Profile of Joachim Messing. PMID- 27382177 TI - Grasses use an alternatively wired bHLH transcription factor network to establish stomatal identity. AB - Stomata, epidermal valves facilitating plant-atmosphere gas exchange, represent a powerful model for understanding cell fate and pattern in plants. Core basic helix-loop-helix (bHLH) transcription factors regulating stomatal development were identified in Arabidopsis, but this dicot's developmental pattern and stomatal morphology represent only one of many possibilities in nature. Here, using unbiased forward genetic screens, followed by analysis of reporters and engineered mutants, we show that stomatal initiation in the grass Brachypodium distachyon uses orthologs of stomatal regulators known from Arabidopsis but that the function and behavior of individual genes, the relationships among genes, and the regulation of their protein products have diverged. Our results highlight ways in which a kernel of conserved genes may be alternatively wired to produce diversity in patterning and morphology and suggest that the stomatal transcription factor module is a prime target for breeding or genome modification to improve plant productivity. PMID- 27382178 TI - DNA binding triggers tetramerization of the glucocorticoid receptor in live cells. AB - Transcription factors dynamically bind to chromatin and are essential for the regulation of genes. Although a large percentage of these proteins appear to self associate to form dimers or higher order oligomers, the stoichiometry of DNA bound transcription factors has been poorly characterized in vivo. The glucocorticoid receptor (GR) is a ligand-regulated transcription factor widely believed to act as a dimer or a monomer. Using a unique set of imaging techniques coupled with a cell line containing an array of DNA binding elements, we show that GR is predominantly a tetramer when bound to its target DNA. We find that DNA binding triggers an interdomain allosteric regulation within the GR, leading to tetramerization. We therefore propose that dynamic changes in GR stoichiometry represent a previously unidentified level of regulation in steroid receptor activation. Quaternary structure analysis of other members of the steroid receptor family (estrogen, androgen, and progesterone receptors) reveals variation in oligomerization states among this family of transcription factors. Because GR's oligomerization state has been implicated in therapy outcome, our findings open new doors to the rational design of novel GR ligands and redefine the quaternary structure of steroid receptors. PMID- 27382179 TI - Resistance mutations generate divergent antibiotic susceptibility profiles against translation inhibitors. AB - Mutations conferring resistance to translation inhibitors often alter the structure of rRNA. Reduced susceptibility to distinct structural antibiotic classes may, therefore, emerge when a common ribosomal binding site is perturbed, which significantly reduces the clinical utility of these agents. The translation inhibitors negamycin and tetracycline interfere with tRNA binding to the aminoacyl-tRNA site on the small 30S ribosomal subunit. However, two negamycin resistance mutations display unexpected differential antibiotic susceptibility profiles. Mutant U1060A in 16S Escherichia coli rRNA is resistant to both antibiotics, whereas mutant U1052G is simultaneously resistant to negamycin and hypersusceptible to tetracycline. Using a combination of microbiological, biochemical, single-molecule fluorescence transfer experiments, and X-ray crystallography, we define the specific structural defects in the U1052G mutant 70S E. coli ribosome that explain its divergent negamycin and tetracycline susceptibility profiles. Unexpectedly, the U1052G mutant ribosome possesses a second tetracycline binding site that correlates with its hypersusceptibility. The creation of a previously unidentified antibiotic binding site raises the prospect of identifying similar phenomena in antibiotic-resistant pathogens in the future. PMID- 27382180 TI - Spectral discrimination in color blind animals via chromatic aberration and pupil shape. AB - We present a mechanism by which organisms with only a single photoreceptor, which have a monochromatic view of the world, can achieve color discrimination. An off axis pupil and the principle of chromatic aberration (where different wavelengths come to focus at different distances behind a lens) can combine to provide "color blind" animals with a way to distinguish colors. As a specific example, we constructed a computer model of the visual system of cephalopods (octopus, squid, and cuttlefish) that have a single unfiltered photoreceptor type. We compute a quantitative image quality budget for this visual system and show how chromatic blurring dominates the visual acuity in these animals in shallow water. We quantitatively show, through numerical simulations, how chromatic aberration can be exploited to obtain spectral information, especially through nonaxial pupils that are characteristic of coleoid cephalopods. We have also assessed the inherent ambiguity between range and color that is a consequence of the chromatic variation of best focus with wavelength. This proposed mechanism is consistent with the extensive suite of visual/behavioral and physiological data that has been obtained from cephalopod studies and offers a possible solution to the apparent paradox of vivid chromatic behaviors in color blind animals. Moreover, this proposed mechanism has potential applicability in organisms with limited photoreceptor complements, such as spiders and dolphins. PMID- 27382181 TI - Probe for the measurement of cell surface pH in vivo and ex vivo. AB - We have developed a way to measure cell surface pH by positioning a pH-sensitive fluorescent dye, seminaphtharhodafluor (SNARF), conjugated to the pH low insertion peptide (pHLIP). It has been observed that many diseased tissues are acidic and that tumors are especially so. A combination of effects acidifies tumor cell interiors, and cells pump out lactic acid and protons to maintain intracellular pH, acidifying the extracellular space. Overexpression of carbonic anhydrases on cell surfaces further contributes to acidification. Thus, the pH near tumor cell surfaces is expected to be low and to increase with distance from the membrane, so bulk pH measurements will not report surface acidity. Our new surface pH-measurement tool was validated in cancer cells grown in spheroids, in mouse tumor models in vivo, and in excised tumors. We found that the surface pH is sensitive to cell glycolytic activity: the pH decreases in high glucose and increases if glucose is replaced with nonmetabolized deoxyglucose. For highly metastatic cancer cells, the pH measured at the surface was 6.7-6.8, when the surrounding external pH was 7.4. The approach is sensitive enough to detect 0.2 0.3 pH unit changes in vivo in tumors induced by i.p. injection of glucose. The pH at the surfaces of highly metastatic cells within tumors was found to be about 6.1-6.4, whereas in nonmetastatic tumors, it was 6.7-6.9, possibly creating a way to distinguish more aggressive from less aggressive tumors. Other biological roles of surface acidity may be found, now that targeted measurements are possible. PMID- 27382182 TI - In situ characterization of the mTORC1 during adipogenesis of human adult stem cells on chip. AB - Mammalian target of rapamycin (mTOR) is a central kinase integrating nutrient, energy, and metabolite signals. The kinase forms two distinct complexes: mTORC1 and mTORC2. mTORC1 plays an essential but undefined regulatory function for regeneration of adipose tissue. Analysis of mTOR in general is hampered by the complexity of regulatory mechanisms, including protein interactions and/or phosphorylation, in an ever-changing cellular microenvironment. Here, we developed a microfluidic large-scale integration chip platform for culturing and differentiating human adipose-derived stem cells (hASCs) in 128 separated microchambers under standardized nutrient conditions over 3 wk. The progression of the stem cell differentiation was measured by determining the lipid accumulation rates in hASC cultures. For in situ protein analytics, we developed a multiplex in situ proximity ligation assay (mPLA) that can detect mTOR in its two complexes selectively in single cells and implemented it on the same chip. With this combined technology, it was possible to reveal that the mTORC1 is regulated in its abundance, phosphorylation state, and localization in coordination with lysosomes during adipogenesis. High-content image analysis and parameterization of the in situ PLA signals in over 1 million cells cultured on four individual chips showed that mTORC1 and lysosomes are temporally and spatially coordinated but not in its composition during adipogenesis. PMID- 27382183 TI - Methylation interactions in Arabidopsis hybrids require RNA-directed DNA methylation and are influenced by genetic variation. AB - DNA methylation is a conserved epigenetic mark in plants and many animals. How parental alleles interact in progeny to influence the epigenome is poorly understood. We analyzed the DNA methylomes of Arabidopsis Col and C24 ecotypes, and their hybrid progeny. Hybrids displayed nonadditive DNA methylation levels, termed methylation interactions, throughout the genome. Approximately 2,500 methylation interactions occurred at regions where parental DNA methylation levels are similar, whereas almost 1,000 were at differentially methylated regions in parents. Methylation interactions were characterized by an abundance of 24-nt small interfering RNAs. Furthermore, dysfunction of the RNA-directed DNA methylation pathway abolished methylation interactions but did not affect the increased biomass observed in hybrid progeny. Methylation interactions correlated with altered genetic variation within the genome, suggesting that they may play a role in genome evolution. PMID- 27382185 TI - Dexter energy transfer pathways. AB - Energy transfer with an associated spin change of the donor and acceptor, Dexter energy transfer, is critically important in solar energy harvesting assemblies, damage protection schemes of photobiology, and organometallic opto-electronic materials. Dexter transfer between chemically linked donors and acceptors is bridge mediated, presenting an enticing analogy with bridge-mediated electron and hole transfer. However, Dexter coupling pathways must convey both an electron and a hole from donor to acceptor, and this adds considerable richness to the mediation process. We dissect the bridge-mediated Dexter coupling mechanisms and formulate a theory for triplet energy transfer coupling pathways. Virtual donor acceptor charge-transfer exciton intermediates dominate at shorter distances or higher tunneling energy gaps, whereas virtual intermediates with an electron and a hole both on the bridge (virtual bridge excitons) dominate for longer distances or lower energy gaps. The effects of virtual bridge excitons were neglected in earlier treatments. The two-particle pathway framework developed here shows how Dexter energy-transfer rates depend on donor, bridge, and acceptor energetics, as well as on orbital symmetry and quantum interference among pathways. PMID- 27382184 TI - Temperate phages both mediate and drive adaptive evolution in pathogen biofilms. AB - Temperate phages drive genomic diversification in bacterial pathogens. Phage derived sequences are more common in pathogenic than nonpathogenic taxa and are associated with changes in pathogen virulence. High abundance and mobilization of temperate phages within hosts suggests that temperate phages could promote within host evolution of bacterial pathogens. However, their role in pathogen evolution has not been experimentally tested. We experimentally evolved replicate populations of Pseudomonas aeruginosa with or without a community of three temperate phages active in cystic fibrosis (CF) lung infections, including the transposable phage, phi4, which is closely related to phage D3112. Populations grew as free-floating biofilms in artificial sputum medium, mimicking sputum of CF lungs where P. aeruginosa is an important pathogen and undergoes evolutionary adaptation and diversification during chronic infection. Although bacterial populations adapted to the biofilm environment in both treatments, population genomic analysis revealed that phages altered both the trajectory and mode of evolution. Populations evolving with phages exhibited a greater degree of parallel evolution and faster selective sweeps than populations without phages. Phage phi4 integrated randomly into the bacterial chromosome, but integrations into motility-associated genes and regulators of quorum sensing systems essential for virulence were selected in parallel, strongly suggesting that these insertional inactivation mutations were adaptive. Temperate phages, and in particular transposable phages, are therefore likely to facilitate adaptive evolution of bacterial pathogens within hosts. PMID- 27382186 TI - Stochastic cycle selection in active flow networks. AB - Active biological flow networks pervade nature and span a wide range of scales, from arterial blood vessels and bronchial mucus transport in humans to bacterial flow through porous media or plasmodial shuttle streaming in slime molds. Despite their ubiquity, little is known about the self-organization principles that govern flow statistics in such nonequilibrium networks. Here we connect concepts from lattice field theory, graph theory, and transition rate theory to understand how topology controls dynamics in a generic model for actively driven flow on a network. Our combined theoretical and numerical analysis identifies symmetry based rules that make it possible to classify and predict the selection statistics of complex flow cycles from the network topology. The conceptual framework developed here is applicable to a broad class of biological and nonbiological far-from-equilibrium networks, including actively controlled information flows, and establishes a correspondence between active flow networks and generalized ice-type models. PMID- 27382187 TI - Bidirectional Crosstalk between C5a Receptors and the NLRP3 Inflammasome in Macrophages and Monocytes. AB - C5a is an inflammatory mediator generated by complement activation that positively regulates various arms of immune defense, including Toll-like receptor 4 (TLR4) signaling. The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is activated by pathogen products and cellular/tissue damage products and is a major contributor of IL-1beta. In this study, we investigate whether C5a modulates lipopolysaccharide- (LPS-) induced NLRP3 inflammasome activation in myeloid cells. Appearance of plasma IL-1beta during endotoxemia was reduced in C5aR1(-/-) mice when compared to wild-type mice. In vitro, C5a significantly enhanced LPS-induced production of IL-1beta in bone marrow Ly6C high inflammatory monocytes, accompanied by augmented intracellular pro-IL-1beta expression. This effect was abolished during p38 blockade by SB 203580 and in the absence of C5aR1. Conversely, C5a suppressed LPS-induced macrophage production of IL-1beta, which was accompanied by attenuated levels of pro-IL-1beta, NLRP3, and caspase-1 expression. C5a's suppressive effects were negated during phosphoinositide 3-kinase (PI3K) inhibition by wortmannin but were largely preserved in the absence of C5aR1. Thus, C5a bidirectionally amplifies TLR4 mediated NLRP3 inflammasome activation in monocytes while suppressing this pathway in macrophages. However, as C5aR1 deficiency attenuates the IL-1beta response to LPS challenge in vivo, our results suggest overall that C5a augments physiologic inflammasome responses. PMID- 27382188 TI - MicroRNA-Regulated Proinflammatory Cytokines in Sarcopenia. AB - Sarcopenia has been defined as the aging-related disease with the declined mass, strength, and function of skeletal muscle, which is the major cause of frailty and falls in elders. The activation of inflammatory signal pathways due to diseases and aging is suggested to reveal the critical impact on sarcopenia. Several proinflammatory cytokines, especially interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), play crucial roles in modulation of inflammatory signaling pathway during the aging-related loss of skeletal muscle. MicroRNAs (miRNAs) have emerged as the important regulators for the mass and functional maintenance of skeletal muscle through regulating gene expression of proinflammatory cytokines. In this paper, we have systematically discussed regulatory mechanisms of miRNAs for the expression and secretion of inflammatory cytokines during sarcopenia, which will provide some novel targets and therapeutic strategies for controlling aging-related atrophy of skeletal muscle and corresponding chronic inflammatory diseases. PMID- 27382189 TI - C-Terminal Alpha-1 Antitrypsin Peptide: A New Sepsis Biomarker with Immunomodulatory Function. AB - Systemic inflammatory response syndrome (SIRS) is a life threatening condition and the leading cause of death in intensive care units. Although single aspects of pathophysiology have been described in detail, numerous unknown mediators contribute to the progression of this complex disease. The aim of this study was to elucidate the pathophysiological role of CAAP48, a C-terminal alpha-1 antitrypsin fragment, that we found to be elevated in septic patients and to apply this peptide as diagnostic marker for infectious and noninfectious etiologies of SIRS. Incubation of human polymorphonuclear neutrophils with synthetic CAAP48, the SNP-variant CAAP47, and several control peptides revealed intense neutrophil activation, induction of neutrophil chemotaxis, reduction of neutrophil viability, and release of cytokines. We determined the abundance of CAAP48 in patients with severe sepsis, severe SIRS of noninfectious origin, and viral infection. CAAP48 levels were 3-4-fold higher in patients with sepsis compared to SIRS of noninfectious origin and allowed discrimination of those patients with high sensitivity and specificity. Our results suggest that CAAP48 is a promising discriminatory sepsis biomarker with immunomodulatory functions, particularly on human neutrophils, supporting its important role in the host response and pathophysiology of sepsis. PMID- 27382191 TI - Semisynthesis of Derivatives of Oleanolic Acid from Syzygium aromaticum and Their Antinociceptive and Anti-Inflammatory Properties. AB - Oleanolic acid is a pentacyclic triterpenoid compound widely found in plants and well known for its medicinal properties. Oleanolic acid (OA) was isolated from the ethyl acetate extract of Syzygium aromaticum flower buds. Semisynthesis afforded both acetate and ester derivatives. The derived compounds were monitored with thin layer chromatography and confirmed with nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), Fourier infrared (FT-IR) spectroscopy, and melting point (Mp). All these compounds were evaluated for their analgesic and anti-inflammatory properties at a dose of 40 mg/kg. Significant analgesic and anti-inflammatory effects were noted for all OA-derived compounds. In the formalin-induced pain test, the derivatives showed better analgesic effects compared to their precursor, whereas, in the tale flick test, oleanolic acid proved to be superior in analgesic effects compared to all its derivatives with the exception of the acetyl derivative. Acute inflammatory tests showed that acetyl derivatives possessed better anti-inflammatory activity compared to the other compounds. In conclusion, semisynthesis of oleanolic acid yielded several derivatives with improved solubility and enhanced analgesic and anti-inflammatory properties. PMID- 27382193 TI - Vitamin D: The Need of the Hour. PMID- 27382192 TI - Pretransplant Immune- and Apoptosis-Related Gene Expression Is Associated with Kidney Allograft Function. AB - Renal transplant candidates present immune dysregulation, caused by chronic uremia. The aim of the study was to investigate whether pretransplant peripheral blood gene expression of immune factors affects clinical outcome of renal allograft recipients. Methods. In a prospective study, we analyzed pretransplant peripheral blood gene expression in87 renal transplant candidates with real-time PCR on custom-designed low density arrays (TaqMan). Results. Immediate posttransplant graft function (14-day GFR) was influenced negatively by TGFB1 (P = 0.039) and positively by IL-2 gene expression (P = 0.040). Pretransplant blood mRNA expression of apoptosis-related genes (CASP3, FAS, and IL-18) and Th1 derived cytokine gene IFNG correlated positively with short- (6-month GFR CASP3: P = 0.027, FAS: P = 0.021, and IFNG: P = 0.029) and long-term graft function (24 month GFR CASP3: P = 0.003, FAS: P = 0.033, IL-18: P = 0.044, and IFNG: P = 0.04). Conclusion. Lowered pretransplant Th1-derived cytokine and apoptosis related gene expressions were a hallmark of subsequent worse kidney function but not of acute rejection rate. The pretransplant IFNG and CASP3 and FAS and IL-18 genes' expression in the recipients' peripheral blood is the possible candidate for novel biomarker of short- and long-term allograft function. PMID- 27382194 TI - Folate Pathway Gene Methylenetetrahydrofolate Reductase C677T Polymorphism and Alzheimer Disease Risk in Asian Population. AB - The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and susceptibility to Alzheimers disease (AD) was controversial in previous studies. The present meta-analysis was designed to investigate the association of MTHFR C677T polymorphism with AD. Nine studies were identified by search of PubMed, Google Scholar, Elsevier, Springer Link databases, up to January 2013. Odds ratios (ORs) with corresponding 95 % confidence interval (CI) were calculated using fixed effects model or random effects model. All statistical analysis was done by Mix version 1.7. MTHFR C677T polymorphism had a significant association with susceptibility to AD in all genetic models (for T vs C: OR 1.29, 95 % CI 1.15-1.44, p < 0.0001; for TT + CT vs CC: OR 1.38, 95 % CI 1.16-1.364, p = 0.0002; for TT vs CC: OR 1.60, 95 % CI 1.25-2.04, p = 0.0001; for CT vs CC: OR 1.28, 95 % CI 1.1-1.53, p < 0.008; for TT vs CT + CC: OR 1.37, 95 % CI 1.12-1.67, p = 0.002). Results from present meta-analysis supported that the MTHFR C677T polymorphism was associated with an increased risk of AD in Asian population. PMID- 27382195 TI - Apolipoprotein A-I: A Molecule of Diverse Function. AB - Apolipoprotein A-I (apo A-I) an indispensable component and a major structural protein of high-density lipoprotein (HDL), plays a vital role in reverse cholesterol transport and cellular cholesterol homeostasis since its identification. Its multifunctional role in immunity, inflammation, apoptosis, viral, bacterial infection etc. has crossed its boundary of its potential of protecting cardiovascular system and lowering cardiovascular disease risk, attributing HDL to be known as a protective fat removal particle. Its structural homology with prostacyclin stabilization factor has contributed to its anti clotting and anti-aggregatory effect on platelet which has potentiated its cardio protective role as well as its therapeutic efficacy against Alzheimer's disease. The binding affinity and neutralising action against endotoxin lipopolysaccharide, reduces the toxic manifestations of septic shock. As a negative acute phase protein, it blocks T-cell signalling of macrophages. However the recently identified anti-tumor activity of apo A-I has been highlighted in various models of melanoma, lung cancer, ovarian cancer, lymphoblastic leukaemia, gastric as well as pancreatic cancers. These cancer fighting effects are directed towards regression of tumor size and distant metastasis by its immuno modulatory activity as well as its clearing effect on serum lysophospholipids. This lowering effect on lysophospholipid concentration is utilized by apo A-I mimetic peptides to be used in retarding tumor cell proliferation and as a potential cancer therapeutic agent. Not only that, it inhibits the tumor associated neo angiogenesis as well as brings down the matrix degrading enzymes associated with tumor metastasis. However this efficient therapeutic potential of apo A-I as an anti tumor agent awaits further future experimental studies in humans. PMID- 27382196 TI - Prophylactic Effects of Garlic Oil and Onion Oil Fractions as Compared to Vitamin E on Rats Orally Fed with Lead Acetate Solution. AB - Heavy metal pollution is a global public health challenge due to its stable and persistent environmental contamination. Of these lead is considered to be one of the most common ubiquitous and industrial pollutants and at low concentration it exerts extensive damages to the tissues. Daily feeding of lead acetate solution (Dose: 10 mg/kg/day) to normal rats for a month adversely altered the parameters of blood, serum and tissues, viz; RBC, WBC, Hb, d- ALAD (Delta amino levulinic acid dehydratase), Pb content, lipids, oxidized lipids (TBARS), vitamins C and E and GSH levels and activities of AST, ALT and antioxidant enzymes viz; catalase, GR, Gpx and SOD. In order to study whether antioxidants have any effect to counteract the toxicity of lead we have selected comparatively better active allium fractions for the study viz: polar fraction of garlic (PFG) and polar fraction of onion (PFO). On feeding of these active fractions of garlic and onion oils i.e. their polar fractions and vitamin E (Dose 100 mg/kg/day) separately for a month along with or without lead acetate to rats each nutraceutical and vitamin E counteracted the adverse effects of Pb significantly (p <= 0.05). Their effects are in the order of PFG > PFO > Vitamin E. All these results point out that garlic and onion oils contain natural disulfoxide compounds which act as antioxidant and anti toxic to lead compounds. Their comparative differences in action may be due to the presence and position of double bonds and disulfide oxide bonds in their molecules. i.e., in PFG the allyl disulfide oxide group is present and in PFO saturated methyl and propyl groups and unsaturated propenyl group are present in place of allyl groups. The former group confers a better antioxidant activity on PFG, while the latter groups confer a lesser activity on PFO. PMID- 27382190 TI - Epithelial Anion Transport as Modulator of Chemokine Signaling. AB - The pivotal role of epithelial cells is to secrete and absorb ions and water in order to allow the formation of a luminal fluid compartment that is fundamental for the epithelial function as a barrier against environmental factors. Importantly, epithelial cells also take part in the innate immune system. As a first line of defense they detect pathogens and react by secreting and responding to chemokines and cytokines, thus aggravating immune responses or resolving inflammatory states. Loss of epithelial anion transport is well documented in a variety of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, pancreatitis, and cholestatic liver disease. Here we review the effect of aberrant anion secretion with focus on the release of inflammatory mediators by epithelial cells and discuss putative mechanisms linking these transport defects to the augmented epithelial release of chemokines and cytokines. These mechanisms may contribute to the excessive and persistent inflammation in many respiratory and gastrointestinal diseases. PMID- 27382197 TI - Hepatoprotective and Nephroprotective Effect of Curcumin Against Copper Toxicity in Rats. AB - Curcumin is a natural anti-inflammatory and antioxidant with several potential health benefits. Although it has been examined in several metals toxicity studies, but its role in the protection against copper toxicity has not been investigated. In this study; the detoxification and antioxidant effect of curcumin were examined to determine its prophylactic/therapeutic role experimentally in rats. Forty albino rats were divided into five groups; control, CuSO4 (4 mg/kg body weight), curcumin (80 mg/kg body weight), curcumin post treatment (CuSO4 for 15 days followed by curcumin for the next 15 days) and curcumin co-treatment (CuSO4 plus curcumin for 30 days). All rats were treated orally by stomach tube for 30 days/once a day. Changes were observed in hepatic marker enzymes such as: aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT), besides the serum total protein, urea and creatinine. Concentration of liver and kidney antioxidants such as: catalase (CAT), superoxide dismutase (SOD), reduced glutathione-(GSH) and malondialdehyde (MDA) were measured. An increased in the activities of liver marker enzymes, urea, creatinine and the MDA contents were detected after exposure to CuSO4. Meanwhile, the activities of serum total protein, hepatic and renal antioxidants were decreased. Changes in all biochemical parameters were alleviated by the post-treatment and co-treatment of curcumin. Our finding suggests that the curcumin showed protective effects on CuSO4-induced hepatotoxicity and nephrotoxicity. PMID- 27382199 TI - Study of Common Genetic Variant S447X in Lipoprotein Lipase and Its Association with Lipids and Lipoproteins in Type 2 Diabetic Patients. AB - Elevated plasma triglyceride and non-esterified fatty acid concentrations may cause insulin resistance and type 2 diabetes mellitus. Lipoprotein lipase (LPL) is a rate-determining enzyme in lipid metabolism. A variant in the LPL gene has been identified which alters the penultimate amino acid Serine at 447 to a stop codon (S447X), and results in a truncated LPL molecule lacking the C-terminal dipeptide Ser-Gly. The present study was designed to evaluate the frequency of S447X variant in the LPL gene and its effect on the lipid and lipoprotein levels in type 2 diabetic subjects. The genotype frequency distributions of type 2 diabetes patients and controls were in Hardy-Weinberg equilibrium. Comparison of the genotype and allelic frequencies of S447X in subjects with type 2 diabetics compared to controls demonstrated no significant difference. In subjects with type 2 diabetics having hypertriglyceridemia (TG >= 150 mg/dl) compared to diabetics with TG level <150 mg/dl, significant difference in genotype frequency was found among these groups, while allelic frequency of X was significantly differed. Logistic regression analysis showed the negative association of LPL S447X variant with TG and VLDL cholesterol, while no association with total cholesterol, HDL cholesterol and LDL cholesterol was found. The lipid levels except for HDL cholesterol were found to be significantly lower in carriers for S447X than wild type in diabetes group. The decreased level of TG and TG rich lipoprotein in subjects with SNP S447X in LPL, predicts anti-atherogenic activity of carriers for S447X variant in general population as well as type 2 diabetic patients. PMID- 27382198 TI - Assessment of Oxidative Stress Markers and Carotid Artery Intima-Media Thickness in Elderly Patients Without and with Coronary Artery Disease. AB - We aimed to assess whether measuring carotid intima-media thickness (CIMT) and oxidative stress markers such as protein carbonyls, malondialdehyde, nitrate and glutathione in plasma of elderly patients without and with coronary artery disease (CAD) identifies early risk for CAD. A total of 50 cases with cardiovascular risk factors over the age of 60 years without CAD, and 50 patients with angiographically documented CAD over the age of 60 years were included in the study. Control group consists of 200 healthy individuals without the risk factors. Demographic details were obtained from all the subjects and CIMT measured by high frequency ultrasound and oxidative stress markers such protein carbonyls, malondialdehyde and total glutathione were determined in plasma by spectrophotometric methods. The distribution of cardiovascular risk factors in without CAD and CAD cases were smokers (16 vs 56 %), hypertension (26 vs 64 %), diabetes (16 vs 56 %) and dyslipidemia (18 vs 58 %) and positive family history (4 vs 38 %). None of the control group had any cardiovascular risk factors. Among the CAD cases, 16 % had single vessel disease, 44 % had double vessel disease and 40 % had triple vessel disease. The CIMT was significantly increased in CAD cases as compared to cases without CAD and healthy controls. On the other hand, CIMT was significantly increased in cases without CAD as compared to healthy controls. CIMT also increased with the duration of diabetes in patients without CAD and severity of disease in CAD cases. The levels of oxidants like plasma malondialdehyde, protein carbonyls, were significantly elevated and antioxidant glutathione levels and nitrate levels were significantly reduced in cases with and without CAD as compared to healthy controls. Oxidative stress markers and CIMT was found to be significantly increased in patients with cardiovascular risk factors like diabetes, family history of CAD, dyslipidemia, hypertension and smoking when compared to patients without risk factors. In patients with diabetes, CIMT increased as duration of disease increases and also in poorly controlled diabetes. In CAD group, when number of vessel involvement (severity of coronary disease) increases, the CIMT also increases confirming that CIMT is a quantifiable risk factor for CAD. PMID- 27382200 TI - Effect of Oral Contraceptive Pills on the Blood Serum Enzymes and DNA Damage in Lymphocytes Among Users. AB - The continuous use of synthetic hormones as contraceptive pill or hormonal replacement therapy among women is increasing day by day. The widespread use of different formulations as oral contraceptives by women throughout their reproductive cycle has given rise to a serious concern for studying the effects of oral contraceptives on enzymatic profile and DNA damage in peripheral blood lymphocytes among users. The present study was carried out on women taking oral contraceptives. The study was based on the questionnaire having the information of reproductive history, fasting, age, health, nature of menstrual cycle, bleeding and other disease. The profile of the blood serum enzymes i.e. alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), aminotransferases (SGOT and SGPT), serum proteins (albumin and globulin) and DNA damage in lymphocytes was studied among users and non-users. The results of the present study suggest that OCs not only effects enzymatic activity but also results in DNA damage that may vary with the duration of using oral contraceptives. A significant increase in LDH, GGT, SGPT, SGOT, globulin and decrease in ALP as well as albumin was found among users as compared to non users. The observed DNA damage was more in users as compared to non-users. Hormonal contraceptives seem to exert DNA damage and also have significant effects on blood serum enzymes. PMID- 27382201 TI - Circulating Thrombotic Risk Factors in Young Patients with Coronary Artery Disease Who Are on Statins and Anti-platelet Drugs. AB - Thrombotic risk factors may contribute to premature coronary artery disease (CAD), in addition to the conventional risk factors. There is paucity of data on studies evaluating the role of thrombotic factors in premature CAD in Indian patients. Thus a case-control study was performed to evaluate the role of thrombotic and atherogenic factors in young patients with angiographically proven CAD who are on treatment with statins and anti-platelet drugs. 152 patients (<=55 years) with angiographically proven CAD and 102 asymptomatic controls were recruited. Clinical and biochemical data were obtained in both groups. Blood levels of thrombotic factors-fibrinogen, antithrombin-III, tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von-Willebrand factor (v-WF), lipoprotein(a) [Lp(a)] and homocysteine were analyzed. Patients had high levels of conventional CAD risk factors (diabetes mellitus, smoking, hypertension, dyslipidemia and positive family history) compared to controls. Logistic regression analysis revealed that low antithrombin-III (odds ratio/OR 11.2; 95 % confidence interval/CI 2.29-54.01), high fibrinogen (OR 6.04; 95 % CI 1.09-33.21) and high Lp(a) (OR 4.54; 95 % CI 0.92-22.56), as important, independent risk factors in patients. PAI-1(OR 0.15; 95 % CI 0.03-0.69) levels were significantly lower in patients. But other thrombotic risk factors studied (t-PA, v-WF and homocysteine) were comparable among patients and controls. The treatment using statins and anti-platelet drugs might be contributing to the control of some of the thrombotic risk factors. The strategies aiming at lowering the levels of thrombotic risk factors along with conventional risk factors may be useful in primary and secondary prevention of CAD. PMID- 27382202 TI - Multiple Biomarkers to Assess the Pathophysiological State in Critically Ill Patients with Sepsis. AB - Sepsis is associated with various metabolic derangements as a consequence of inflammatory response, ischemia and oxidative stress. Four parameters of relevance are procalcitonin (PCT), ischemia modified albumin (IMA) pH and lactate. The study was carried out to highlight the concomitant occurrence of sepsis, ischemia and lactic acidosis, all of which could have deleterious effects on organ function. 26 critically ill patients with a provisional diagnosis of sepsis were the test subjects. The control group had 25 apparently healthy volunteers. PCT, lactate and IMA were assayed. PCT was estimated on an automated analyser using electro-chemiluminescence. Lactate and pH were estimated on a blood gas analyzer. Serum IMA was estimated spectrophotometrically by Albumin Cobalt Binding Test. Statistical tools like students 't' test and Venn diagram were employed to depict the outcome of the study. All critically ill patients had significantly higher IMA levels (0.96746 +/- 0.73407) as compared to the control group (0.00728 +/- 0.00895) with a p value of <0.0001. The Venn diagram was used to depict the finding that all 26 test subjects had elevated levels of IMA, of which PCT was elevated in 22 and lactate in 20. Both PCT and lactate were abnormal in 17 patients. The most significant observation was that all critically ill patients, irrespective of the presence of sepsis or lactic acidosis had elevated levels of IMA which is clearly indicative of the ubiquitous presence of oxidative stress. The Venn diagram is an elegant representation of the concurrent multiple pathophysiological processes which occur in critically ill patients. PMID- 27382203 TI - Association of the 12669G>A Apolipoprotein B Gene Polymorphism with Apo-B Serum Level and Lipid Profile in Patients with Coronary Artery Disease Comparing with Individuals Without Coronary Artery Disease in Zanjan Population of Iran. AB - Atherosclerosis is a pathologic disorder which has an important role in the occurrence of coronary heart disease. It is determined as a focal, inflammatory proliferative response to several types of endothelial damage. Apolipoprotein B which is a requirement in the sustenance of cholesterol homeostasis, and is the major protein component of low density lipoprotein, characterized by multitude polymorphic sites, one of which (12669G>A) is related to the levels of serum lipid profiles, coronary artery disease and/or myocardial infarction. One Common polymorphism which is more important in this process is 12669G>A that is appraised in this research. We recruited 80 patients from the Mousavi hospital, Zanjan, Iran, diagnosed with coronary artery disease by the clinician on the basis of clinical symptoms, echocardiogram result, and angiography. Seventy-seven healthy individuals without any evident symptoms of Coronary stenosis and any past history of the disease were taken as controls from the general population. We carried out PCR using specific primers. Then, we digested PCR product by RFLP. Lipid parameters by biochemical methods and Apolipoprotein B serum level by immunoturbidometry method were done. Genotype frequencies for 12669G>A polymorphism were determined: 55 % R+R+, 45 % R+R- in case group, and 55.8 R+R+, 44.2 % R+R- in controls. The R-R- genotype was not seen. There was no significant relationship between this polymorphism and the risk of Coronary stenosis (P = 0.6). In the present study, higher plasma levels of cholesterol and low density lipoproteins in the subjects with R+R- genotype were found while there was no association between this polymorphism and coronary stenosis with >=50 % in the Zanjan population. PMID- 27382204 TI - Altered Erythrocyte Glycolytic Enzyme Activities in Type-II Diabetes. AB - The activity of enzymes of glycolysis has been studied in erythrocytes from type II diabetic patients in comparison with control. RBC lysate was the source of enzymes. In the diabetics the hexokinase (HK) activity increased 50 % while activities of phosphoglucoisomerase (PGI), phosphofructokinase (PFK) and aldolase (ALD) decreased by 37, 75 and 64 % respectively but were still several folds higher than that of HK. Hence, it is possible that in the diabetic erythrocytes the process of glycolysis could proceed in an unimpaired or in fact may be augmented due to increased levels of G6P. The lactate dehydrogenase (LDH) activity was comparatively high in both the groups; the diabetic group showed 85 % increase. In control group the HK, PFK and ALD activities showed strong positive correlation with blood sugar level while PGI activity did not show any correlation. In the diabetic group only PFK activity showed positive correlation. The LDH activity only in the control group showed positive correlation with marginal increase with increasing concentrations of glucose. PMID- 27382205 TI - Effect of Oestrogen on Altering the Serum and Urinary Levels of Calcium, Phosphate and Magnesium in Hysterectomised Women Compared to Natural Menopausal South Indian Women: A Case Control Study. AB - Given the paucity of studies conducted to know the effect of suddenness and earlier onset of endocrinological changes associated with hysterectomy, on the serum and urinary levels of calcium, magnesium and phosphate the present study was conducted to compare the levels of calcium, magnesium and phosphate in serum and urine of hysterectomised and natural menopausal south Indian women. This is a cross-sectional observational study. The study included three groups of 30 healthy premenopausal, 30 early surgical menopausal and 30 natural post menopausal women. Women suffering from any endocrine disease were excluded. Analysis was performed in serum and urine sample. The levels of calcium, magnesium and phosphate in serum and calcium/creatinine, magnesium/creatinine and phosphate/creatinine ratio were estimated in urine by spectrophotometric method. Hysterectomised women (serum calcium: 8.7 +/- 0.09 mg/dl; urine calcium/creatinine: 0.16 +/- 0.02) have significantly low serum calcium (p < 0.001) and high urinary calcium/creatinine (p = 0.002) ratio and post menopausal women (serum magnesium: 2.1 +/- 0.03; serum phosphate: 4.4 +/- 0.16; urinary calcium/creatinine: 0.17 +/- 0.02; urinary magnesium/creatinine: 0.09 +/- 0.01) have significantly high serum magnesium (p = 0.016), serum phosphate (p = 0.043) and high urinary calcium/creatinine (p = 0.002), magnesium/creatinine ratio (p = 0.025) compared to healthy pre menopausal women. Post menopausal women (serum calcium: 9.1 +/- 0.08) have significantly high serum calcium and phosphate compared to hysterectomised women (serum phosphate: 3.93 +/- 0.11). Hysterectomised women have significantly low serum calcium, oestrogen and high urinary calcium/creatinine ratio compared to healthy premenopausal women and low serum calcium and low serum phosphate compared to natural postmenopausal women. Natural postmenopausal women had low serum oestrogen and high serum magnesium, serum phosphate, urinary calcium creatinine ratio and urinary magnesium creatinine ratio compared to healthy premenopausal women. PMID- 27382206 TI - Assessment of Hematological Parameters in Pulmonary Tuberculosis Patients. AB - The aim of the study was the assessment of hematological parameters in pulmonary tuberculosis patients. Forty patients diagnosed with tuberculosis were recruited from the Institute of Thoracic Medicine on the basis of history, clinical examination, chest radiography, sputum examination and related laboratory parameters and were compared with age and sex matched healthy volunteers (n = 40). Hematological parameters and CRP in tuberculosis patients were determined. The mean values for serum hemoglobin level, RBC count and platelet count in PTB was found to be less (p < 0.001). Erythrocyte sedimentation rate (ESR), plasma C reactive protein, WBC count in PTB subjects was increased (p < 0.001 for ESR & CRP, p < 0.05 for WBCs) and all were statistically significant. This study demonstrated that serum hemoglobin level, RBC count and platelet count was decreased in tuberculosis patients whereas ESR, CRP and WBC count was increased when compared with healthy controls. PMID- 27382207 TI - Differential Expressions of p53, p53R2, hRRM2 and PBR in Chronic Lymphocytic Leukemia: A Correlation with Intracellular Cholesterol. AB - Regulation of intracellular cholesterol homeostasis exists under balance between intracellular biosynthesis and uptake from extracellular origin by cell surface transport proteins. Expected role of cholesterol on either tumor suppressor gene and/or DNA synthesis has been aimed in the present study to explore intracellular cholesterol homeostasis in CLL subjects. Higher expressions of p53R2 (p53 dependent subunit of ribonucleotide reductase) and p53 were found in lymphocytes of chronic human lymphocytic leukemia as comparison to their normal counterparts. Inverse relation was found with p53 independent R2 subunit (in human hRRM2) of ribonucleotide reductase, which was found to be decreased from its control group. More expression of peripheral type benzodiazepine receptor, a cholesterol transporter, was noticed in isolated nuclear fraction with simultaneous increase of cholesterol concentration in cytoplasmic and nuclear compartments. A parallel increase of cholesterol in cell nucleus with increased p53R2 expression shows priority of the involvement of cholesterol in the process of cell replication. PMID- 27382208 TI - Effect of Ubiquinol on Serum Reproductive Hormones of Amenorrhic Patients. AB - In neuroendocrine system the increase in oxidative status is produced by a glucocorticoid-dependent and transcriptional increase in pro-oxidative drive, with concurrent inhibition of the antioxidant defense system, ultimately leading to increased neuronal cell death. Functional hypothalamic disturbances and neuroendocirne aberrations have both short and long term consequences for reproductive health. Understandably, an impaired or diminished hypothalamic pituitary-ovarian axis leads to anovulation and hypoestrogenism. Anovulation is directly linked to the neurohormonal and hormonal background of Functional Hypothalamic Amenorrhea. Impairment of pulsatile Gonadotropin Releasing Hormone secretion causes the impairment of pulsatile Lutenizing Hormone (LH) and Follicle Stimulating Hormone (FSH) secretion. The importance of oxidative stress in various pituitary disorders suggesting a possible clinical usefulness of antioxidant molecules like the lipophilic antioxidant Ubiquinol. Coenzyme Q10 or Ubiquinol is an essential part of the cell energy-producing system of mitochondria. However, it is also a powerful lipophilic antioxidant, protecting lipoproteins and cell membranes from autooxidation. Due to these unique actions Ubiquinol is used in clinical practice as an antioxidants for neurodegenerative diseases. So to identify the role of Ubiquinol on reproductive hormones FSH and LH, we have included 50 infertile patients of age group of 20-40, which are mostly amenorrhic. Out of 50 only 30 patients were in continuous follow up after supplementing them with 150 mg of Ubiquinol every day for 4 months. The hormonal levels were estimated by Enzyme Linked Immuno Sorbent Assay technique at follicular phase. The result suggests that FSH concentration is increased up to three times (from 3.10 +/- 2.70 to 10.09 +/- 6.93) but remains within the normal limit (P < 0.05). LH values were found doubled (P < 0.05) than its normal range (from 14.83 +/- 10.48 to 27.85 +/- 22.30). The Prolactin values were decreased while Progesterone values were high but not in the significant range (P > 0.05). The supplementation of 150 mg of Ubiquinol may reduce the oxidative stress in neuroendocrine system which further improves the function of diminished HPA axis. Hence increased level of FSH and LH may be due to reduced oxidative stress by Ubiquinol. PMID- 27382209 TI - Microalbuminuria in Obese Young and Middle Aged Population: A Potential Marker of Cardiovascular Risk. AB - Microalbuminuria is an established cardiovascular risk indicator in diabetes, hypertension and the general population. There is lack of information on MAU in healthy obese Indian adults and an ongoing debate whether obese adults deserve targeted identification and clinical intervention for MAU and prediabetes. We aimed to screen the healthy obese, young (group I) and middle aged (group II) adults for prevalence of MAU and prediabetes and study its association with Framingham risk score. The study included 50 healthy obese young (20-30 years) and middle aged adults (31-50 years), attending the outpatient clinic of Dept. of Medicine for a duration of 2 months (July-August). The patients were screened for fasting blood sugar, lipid profile and MAU. Of the total patients 28 % had MAU, 32.14 % of which had prediabetes and 33.33 % had diabetes whereas 10 % were normoglycemic. The group I patients had 50 % cases of MAU and group II had 25 % patients with MAU. Group II 63.63 % pre-diabetics. The values of MAU obtained were correlated with age, gender, body mass index, systolic and diastolic blood pressure, FBS, waist to hip ratio using Pearson's Coefficient (p < 0.05). The 10 year CVD risk calculated using FRS in subjects with MAU was higher as compared to those without MAU. Thus we conclude that Indian, young and middle aged obese adults to be at a risk of prediabetes, MAU and CV risk warranting their routine screening for better clinical outcomes. PMID- 27382210 TI - Alkaptonuria: A Case of Familial Inheritance from Hangarki Village in Dharwad District of Karnataka. AB - Alkaptonuria is a genetic disorder, unknown to the general public and ignored by general physicians due to lack of awareness of its high prevalence. Increasing incidences of familial inheritance are recorded. A 41 years 8 months male with the swollen knee, chronic mechanical pain, restricted limping walk and tingling sensation in the limb. Also, has a complaint of the stiffness of back in the morning, which gets relieved by movement. Mild hyper pigmentation of pinna and sclera of eye. X-ray report reveals osteoarthritis of the knee and thoracic kyphosis. After considering clinical finding, report of radiological investigation and Biochemical test results, patient was diagnosed as a case of Alkaptonuria. Screening of entire family revealed a typical case of familial inheritance. Hidden familial inheritance can be disclosed by mass screening of families and medical awareness. PMID- 27382211 TI - Infantile Tremor Syndrome Persistence in Era of Development: An Old Story. AB - Infantile tremor syndrome is seen worldwide more commonly in the developing countries. Although various protein energy malnutrition awareness programme being run in many of these countries including India yet there is persistence of this disease. Here we present a case of 13 month old female child who visited RAPCC paediatrics OPD of Govt. Wenlock Hospital Mangaluru with history of respiratory distress, fever, tremor in limbs and loss of milestones. On examination she had pallor, hyper pigmentation in axilla and toes. Investigatory findings showed megaloblastic erythroid hyperplasia, hemoglobin- 1.6 g % and CT scan of brain showed central atrophic changes. PMID- 27382212 TI - Social Egg Freezing: Developing Countries Are Not Exempt. AB - Non-medical egg freezing has only been available for about the last 5 years, as new vitrification techniques have made the success rates for actual conception more reliable than the earlier method of slow freezing. The improved outcomes of new technologies of vitrification and intra-cytoplasmic sperm injection (ICSI) have led to the marketing of egg freezing for non-medical reasons, whereby women are offered the possibility of preserving their eggs until such time as they wish to have a child. For many women today, it is not cancer but the simple passage of time that robs them of their chance of motherhood. Social, educational, emotional and financial pressures often lead them to delay trying to start a family until their late thirties, by which time the chance of success is very low. Women at age 40 face a 40 % chance of miscarriage if they can get pregnant at all, and by the age of 45, the risk of miscarriage is 75 %. Donor eggs are not an option for many because of supply constraints and ethical and cultural concerns. Freezing a woman's eggs at age 30 literally "freezes in time" her fertility potential and gives her the chance of a healthy pregnancy at a time of her choosing. Despite the initial reactions of disapproval, more and more fertility clinics are now offering oocyte cryopreservation to healthy women in order to extend their reproductive options. This procedure is now becoming popular even in developing economies, and egg freezing in major Indian Metros is now routine. PMID- 27382213 TI - A Cross-Sectional Study of Postpartum Changes in Bone Status in Indian Mothers. AB - BACKGROUND: Bone turnover is high during lactation. However, studies on bone status of Indian urban mothers are scarce. Hence, the objective was to conduct a cross-sectional study on the lactation-related changes in bone health status of Indian mothers postpartum using Dual X-ray Absorptiometry (DXA) at 3 time points: within a week of delivery, at 1- and 3-years postpartum. We also explored the association of dietary calcium intake, physical activity, serum vitamin D status, and dietary traditional food supplements (Dietary Food supplements) with bone health. METHODS: A cross-sectional study was conducted; 300 full-term, healthy primiparous women (28.6 +/- 3.4 year) were randomly selected and categorized into 3 groups: 128 mothers within 7 days of delivery (Group A), 88 with 1-year-old children (B), and 84 with 3-year-old children (C). Anthropometry, lactation history, physical activity, diet, biochemical tests (vitamin D, parathyroid hormone), body composition, areal bone mineral density (a-BMD) at total body (TB), AP spine (APS), and dual neck femur (DF) were assessed by DXA (GE-Lunar DPX). RESULTS: Significantly higher APS-BMD (mean +/- SD) was observed in Group C (1.107 +/- 0.098 g/cm(2)) than that in A (1.045 +/- 0.131 g/cm(2)) (p < 0.05). When adjusted for breastfeeding practices, mean (+/-standard error) APS-BMD was lowest in women in Group A (1.024 +/- 0.013 g/cm(2)), but was higher at 1-year (1.079 +/- 0.02 g/cm(2)) and at 3-years postpartum (1.111 +/- 0.019 g/cm(2)), though differences were significant only between groups A and C (p < 0.05). Most mothers from all 3 groups consumed inadequate amount of nutrients except dietary fat and showed low physical activity. Multiple regression analysis indicated that dietary calcium, moderate physical activity, serum vitamin D, and consumption of dietary food supplements were not significant predictors of APS-BMD (p > 0.1). CONCLUSION: Prevalence of nutrient and vitamin D deficiencies, low physical activity, and poor sunlight exposure were major concerns in Indian lactating mothers; improvement in bone mass at APS was observed at 3-years which was most likely due to physiologic changes. PMID- 27382214 TI - Outcome of Diabetic Pregnancies in a Tertiary Referral Centre, Varanasi. AB - AIM: The study was done to determine the maternal and fetal outcome of pregnancies complicated by maternal diabetes either Gestational Diabetes Mellitus (GDM) or preexisting (type 1 or type 2) diabetes over a period from March 2011 to Feb 2013 in a tertiary care hospital, Varanasi. METHODS: This is a retrospective audit of the maternal and fetal outcome of women who presented to the Sir Sundar Lal Hospital, Department of Obstetrics and Gynaecology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India from March 2011 to Feb 2013, with GDM or pre-existing type 1 or type 2 Diabetes with pregnancy. The audit group comprised 65 pregnancies (67 babies), of whom 27 had preexisting diabetes and 38 cases developed gestational diabetes. Pregnant women who were found to be diabetic preconceptionally or in the first trimester were classified as 'pre existing diabetes'. RESULTS: There were total of 65 diabetic women in this retrospective study, 39 women were GDM (60 %) while 26 women (40 %) were having pre-existing diabetes (24 type 1 diabetes and 2 women were in type 2 diabetes group). There were 35 multigravid women (53.85 %) and 30 primigravid women (46.15 %). There were 39 (60 %) women on Insulin. There were 42 Lower Segment Caesarean Section (64.62 %) and 23 Spontaneous Vaginal Delivery (35.38 %). In fetal and neonatal complications, there were three still births, one case of intrapartum death, and one case of shoulder dystocia. Fetal anomalies were less frequent, one case of Gastroschisis with Hydrocephalus associated with Menigomyelocoele, there was one case of isolated Hydrocephalus, and there was also one case of Truncus arteriosus. CONCLUSIONS: The study analyses maternal and fetal complication in the GDM group and also preexisting diabetes group. In our centre, the 60 % women were GDM while 40 % were having pre-existing diabetes. Total rate of fetal/neonatal complication rate was 7.69 % and of congenital anomaly rate it was 9.23 %. Proportion of still birth, Intrauterine death, and congenital malformations was higher in the pre-existing diabetes group although the data are not large enough to draw a statistically significant conclusion. LSCS rate was little higher in the GDM group (69.23 %) in comparison to the preexisting diabetes group where it was 57.69 %. SVD (Spontaneous Vaginal Delivery) rate was 30.77 % in GDM and 42.31 % in the pre-existing diabetes group. HbA1c was within normal range 84.62 % of GDM group while in 15.38 % it was raised >6 %. In the pre existing diabetes group, only 19.23 % of women had HbA1c within acceptable range and 80.77 % had it >6. The aim of St Vincent Declaration is to 'achieve pregnancy outcome in the diabetic woman that is similar to that of the non-diabetic woman.' But, so far we have not been able to achieve this. Our HbA1c level is remarkably high in the pre-existing diabetes group. Only 3 out of 65 patients' women took Folic Acid periconceptionally. We need to work to achieve it our best. It is well known that insulin treatment during pregnancy results in reduction in the rate of macrosomia, fetal/neonatal, and maternal complications. Therefore, we need to use insulin judiciously and advocate its usage in the situations where it is needed. PMID- 27382215 TI - Predictors of Success of a Single-Dose Methotrexate in the Treatment of Ectopic Pregnancy. AB - BACKGROUND: Ectopic pregnancy (EP) is the commonest cause of maternal mortality related death in the first trimester. Methotrexate (MTX) remains the first-line treatment in optimally selected patients. OBJECTIVE: To evaluate the success rate and predictors of success of a single-dose MTX treatment in EP. SUBJECTS AND METHOD: We studied retrospectively 109 patients with unruptured EP who were treated with Intramuscular MTX administered in a dose of 50 mg/m(2) on days 0 and in additional doses on day 7 if beta-hCG levels did not decrease by 15 % during the follow-up period. The study was conducted at the Maternity and Children Hospital Buraidah, Saudi Arabia from June 2013 to December 2013. Pretreatment beta-beta-hCG, EP mass diameter, peritoneal fluid, and fetal cardiac activity were evaluated. The main outcome measures were success rate, the predictors of success without surgical treatment. RESULT: Under this regime, the overall success rate was 60.6 % of patients. Of the failure group, only 4.7 % of patients experienced rupture of EP. No side effects were reported. The main predictors of failure were initial beta-hCG value >= 3.500 mIU/mL OR 4.11 (1.646-12.248, 0.043) and EP diameter 3.73 (1.646-12.10, p = 0.003). CONCLUSION: The success rate of MTX in this study was 60.6 %, and the initial beta-hCG concentration and EP diameter were the best predictors of successful treatment with MTX. Furthermore, MTX should be offered only to those patients with beta-hCG <2,000 mIU/mL and EP mass size <3.5 cm. PMID- 27382216 TI - A Study of Incomplete Abortion Following Medical Method of Abortion (MMA). AB - BACKGROUND: Medical method of abortion (MMA) is a safe, efficient, and affordable method of abortion. However, incomplete abortion is a known side effect. OBJECTIVE: To study incomplete abortion due to medication abortion and compare to spontaneous incomplete abortion and to study referral practices and prescriptions in cases of incomplete abortion following MMA. METHOD: Prospective observational study of 100 women with first trimester incomplete abortion, divided into two groups (spontaneous or following MMA), was administered a questionnaire which included information regarding onset of bleeding, treatment received, use of medications for abortion, its prescription, and administration. Comparison of two groups was done using Fisher exact test (SPSS 21.0 software). RESULTS: Thirty percent of incomplete abortions were seen following MMA; possible reasons being self-administration or prescription by unregistered practitioners, lack of examination, incorrect dosage and drugs, and lack of follow-up. Complications such as collapse, blood requirement, and fever were significantly higher in these patients compared to spontaneous abortion group. CONCLUSION: The side effects of incomplete abortions following MMA can be avoided by the following standard guidelines. Self medication, over- the-counter use, and prescription by unregistered doctors should be discouraged and reported, and need of follow-up should be emphasized. PMID- 27382217 TI - Predictive Value of Cerebroplacental Ratio in Detection of Perinatal Outcome in High-Risk Pregnancies. AB - OBJECTIVE: To assess the predictive value of cerebroplacental ratio (i.e., S/D ratio of middle cerebral artery to S/D ratio of Umbilical artery) in detection of perinatal outcome in high-risk pregnancies. MATERIAL AND METHOD: This retrospective study was conducted on 150 patients between 28 and 40 weeks of gestation (25 low risk and 125 high risk) who attended OPD and indoor wards of Teerthanker Mahaveer medical college and research center, Moradabad. All patients had serial color Doppler ultrasounds done after taking informed consent which was repeated at 2 weeks interval, and data were collected with regard to perinatal outcome. RESULT AND CONCLUSION: Cerebroplacental ratio is having higher sensitivity and negative predictive value in detection of IUGR, Meconium aspiration syndrome, operative interference for fetal distress, and NICU admissions in comparison to its components. So, better prediction of neonatal outcome can be done by C/U ratio. PMID- 27382218 TI - Morbidities in Neonates Delivered Electively at Early Term. AB - OBJECTIVE: To study the incidence of elective cesarean deliveries at term and to correlate their neonatal outcomes at different gestational ages (37(0/7) 40(6/7)). METHODS: Outcomes including the rate of NICU admissions, usage of ventilator/CPAP, and other morbidities were analysed and compared with the gestational age during the study period from January 2012 to April 2013. RESULTS: The incidences of elective deliveries at 37, 38, 39, and 40 weeks of gestation were 10.6, 29.7, 28, and 31.5 %, respectively. NICU admissions-RR 3.94 (95 % CI 1.92-8.09), respiratory distress-RR 5.255 (95 % CI 1.9-14.4), ventilatory usage, and hospitalization stay (P value < 0.05) were higher in neonates born at 37(0/7 6/7) versus 39(0/7-6/7) weeks (least morbidity group). CONCLUSION: Despite recommendations, more than one-third of term babies are delivered electively at <39 weeks. The fivefold augmented respiratory morbidity and fourfold increased NICU admissions in early term neonates, and the least morbidity in neonates delivered at 39 weeks emphasize the importance of restricting the non emergent/elective deliveries to 39 weeks of gestation. PMID- 27382219 TI - Preoperative Use of 10-mg Metoclopramide and 50-mg Dimenhydrinate in the Prophylaxis of Postoperative Nausea and Vomiting in Elective Caesarean Births: A Prospective Randomized Clinical Study. AB - BACKGROUND: The purpose of this study was to assess the efficacy and outcomes of preoperative prophylactic metoclopramide and dimenhydrinate use in elective cesarean births. METHODS: Participants (n = 84) scheduled for elective cesarean births were randomized equally into placebo (10 cc 0.9 % NaCl), 10-mg metoclopramide or 50-mg dimenhydrinate groups. Oral alimentation was prohibited 8 h before the surgery; however, patients continued drinking water until 4 h before surgery. Placebo and antiemetics were administered 1 h before the anticipated procedure in a 5-ml syringe. In metoclopramide and dimenhydrinate group, an ampoule of the agents was completed to 5 ml by adding 0.9 % NaCl. In the control group 5 ml of 0.9 % NaCl was used. All prophylactic agents were administered intramuscularly. All patients received a general anesthesia. The placebo group (control group) was compared with the metoclopramide and dimenhydrinate groups. RESULTS: Demographic data including maternal age, height, weight, body mass index, gravidity, parity, miscarriage, induced abortion, the number of offspring, and the medical history did not show significant differences among the three groups. Postoperative nausea, vomiting, and the use of rescue medication ratios were significantly lower in metoclopramide and dimenhydrinate groups compared with the placebo group (p < 0.05); however, the difference between the metoclopramide and dimenhydrinate groups was not significant (p > 0.05). CONCLUSION: Dimenhydrinate and metoclopramide significantly decrease postoperative nausea, vomiting, and the need for rescue antiemetic medication. Both agents have similar efficacy and may be used as an alternative to each other. PMID- 27382220 TI - Implementation of WHO Near-Miss Approach for Maternal Health at a Tertiary Care Hospital: An Audit. AB - OBJECTIVE: The objective of this study was to evaluate severe maternal outcomes (including maternal deaths and maternal near-miss cases). MATERIALS & METHODS: A prospective study of severe maternal outcomes (including maternal deaths and maternal near-miss cases) from May 2012 to April 2013 was performed. For each woman, data were collected on the occurrence of selected severe pregnancy-related complications, the use of critical interventions, and admissions to intensive care unit. RESULTS: The total number of deliveries were 2340. The number of maternal deaths was three. The natures of the near-miss cases during the study period were recorded. Prevalence of SAMM (severe acute maternal morbidity) was 2.025 %. CONCLUSION: In areas where the maternal mortality is low, there is a need to shift focus to maternal near-miss cases or SAMM, which is a useful adjunct to maternal death enquiries. PMID- 27382221 TI - Comparison Between Concurrent EBRT and ICA with Conventional EBRT Followed by ICA in Cervical Cancer. AB - INTRODUCTION: In carcinoma of cervix, if overall treatment time (OTT) is prolonged beyond 6 weeks, then the total dose required to achieve a given probability of tumor control is to be increased by 0.6 Gy for each day of prolongation, to control the accelerative repopulation of the cells, i.e., 1 % loss of tumor control, and to avoid increased treatment delays and drop outs due to the prolonged gap between EBRT and intracavitary brachytherapy (ICBT). OBJECTIVES: To evaluate local disease control and early complications of concomitant HDR-ICBT with EBRT and thereby decrease the OTT in I B-III B stage carcinoma cervix. METHODS: Fifty patients of carcinoma cervix (FIGO-I B/III B) were randomly divided into two groups: the study group treated with concomitant EBRT and HDR-ICBT (EBRT = 50-50.4 Gy/25-28 Fr, HDR 7 Gy in 3 Fr during the 3rd, 4th, and 5th weeks), EBRT and weekly cisplatin were not given on the day of HDR ICBT; and the control group treated with EBRT followed by HDR-ICBT and weekly cisplatin. Acute reactions and local disease response were compared after treatment and at 6-month follow-up. RESULTS: Medians of OTTs were 42 and 63 days in the study and the control groups, respectively. Dysuria and diarrhoea incidences were more in the study but manageable. At the completion of the treatment, there were 92 and 80 % complete responses; 4 and 4 % partial responses; and 4 and 16 % stable diseases in the study group and the control group, respectively. DFSs (disease free survivals) at 6-month follow-up were, respectively, 96 and 84 %, and most of the stable diseases were observed in stage III B. CONCLUSIONS: Response was better in the study group but statistically insignificant, acute reactions were manageable, and there was decrease in drop outs due to completion of treatment at a stretch, but larger number of patients and longer follow-up are required to arrive at concrete conclusions. PMID- 27382223 TI - Uterine Arteriovenous Malformation: Case Series and Literature Review. AB - BACKGROUND: Uterine AV malformation is a rare cause of torrential post-abortal hemorrhage, which can present with varying grades of severity. Diagnosis requires a high degree of suspicion and is done with ultrasound and Doppler. CASE SERIES: In our institution, during the period 2008-2013, five cases of symptomatic uterine AVMs have been reported. All of them were in the reproductive age group (22-36 years), presenting with a history of miscarriage or termination of pregnancy for which curettage was done. The presentation was with recurrent bouts of torrential bleeding, some triggered by second curettage, and not controllable with regular measures. Diagnosis was by ultrasound-gray scale, color Doppler, and spectral Doppler. The time interval between the onset of symptoms and the primary curettage was 8-89 days; four patients underwent selective arterial embolization, and one patient opted for hysterectomy. On follow-up, all the four patients are presently free of symptoms; two of them conceived within 2 years of the procedure and carried the pregnancy to term-one resulting in a live-birth and the other intrauterine death. CONCLUSION: Uterine AV malformation should be thought of as a differential diagnosis in all cases presenting with bleeding after miscarriage or curettage, since diagnosis is simple and treatment by selective arterial embolization saves morbidity of surgery and anesthesia, and more importantly reduces hospital stay and the absence from work. PMID- 27382222 TI - Laparoscopic Hysterectomies: Our 10 Years Experience in a Single Laparoscopic Center. AB - STUDY OBJECTIVE: To evaluate the association between outcomes of laparoscopic hysterectomy with respect to clinical factors, intraoperative variants, and post operative complications. DESIGN: The study conducted was retrospective (Canadian Task Force Classification II-1). SETTING: The set used in this study was a gynecological laparoscopic centre. PATIENTS: The present study included 858 women who underwent laparoscopic hysterectomies with or without bilateral/unilateral salpingo-oophorectomy, from December 2004 to May 2014. INTERVENTIONS: Eight hundred and sixteen patients underwent total laparoscopic hysterectomy, 14 patients underwent subtotal laparoscopic hysterectomy, 20 patients underwent laparoscopic-assisted vaginal hysterectomy, and 8 patients underwent laparoscopic radical hysterectomy with bilateral pelvic lymph node dissection. MEASUREMENTS AND MAIN RESULTS: All surgeries were performed by the same surgeon, using the same surgical technique. The medical records were reviewed, and data were collected with respect to age, indications, type of surgery performed, intraoperative variants, and post-operative complications. Patient average age was 44.9 +/- 6.2 years. Most common indication for benign TLH was leiomyoma of 54.4 %. Indications for laparoscopic radical hysterectomy were early stage endometrial cancer (n = 5) and early stage cervical cancer (n = 3). The maximum uterine size operated on was from 20-26 weeks, 4.9 % (n = 42). 9.7 % had previous abdominopelvic surgery. Fifty three % underwent unilateral/bilateral salpingo oophorectomy. Conversion rate was 0.93 % (n = 8). The minimum and maximum operating time during the total study period was 20 min-2 h. The major complication rates were 0.9 % (n = 8). The hospital stay was not more than 2 days. CONCLUSION: In our experience of 858 laparoscopic hysterectomies, 850 were done for benign indications, and 8 done for malignancies. TLH can be performed more safely and under vision, with less blood loss, early post-operative recovery, less post-operative infection, and less complication rate. PMID- 27382224 TI - Comparative Study of Cesarean Myomectomy with Abdominal Myomectomy in Terms of Blood Loss in Single Fibroid. AB - OBJECTIVE: In this study, we evaluate the safety and feasibility of cesarean myomectomy and compare this procedure with abdominal myomectomy in single fibroid, in terms of blood loss and postoperative complications. METHODS: Thirty three patients who underwent cesarean myomectomy from June 2006 to 2012 in Amrita Institute of Medical Sciences, were included in the study. Almost an equal number of patients who underwent abdominal myomectomy (32) in the same period were included. Women are divided into two groups: group 1-cesarean myomectomy, group 2 abdominal myomectomy. RESULTS: Mean age of the women was comparable; mean gestational age in group 1 was 37.97 +/- 1.57 weeks; and 60 % were primiparous. Hemoglobin (Hb) drop postoperatively was compared between the groups, and there was no significant difference. Though there was statistically significant difference among the groups regarding the size of fibroids, the main outcome measure of the study, the Hb drop was comparable between group 1 and 2. There is statistically significant difference in the Hb difference with increasing mean diameter of the fibroids. As the size increases, Hb drop also increases indicating the increasing blood loss. The measures used to reduce blood loss such as vasopressin instillation and stepwise devascularization influence the blood loss, and P value shows borderline significance. There was no difference in Hb drop among the groups according to the type of fibroids. But more subserous fibroids were removed in group 1, whereas more intramural fibroids were removed in group 2. CONCLUSION: Cesarean myomectomy can be safely done in single fibroids and is comparable to abdominal myomectomy in terms of blood loss. PMID- 27382225 TI - A Rare Case of Perforation Following PPIUCD Insertion. PMID- 27382226 TI - Precycle Estradiol in Synchronization and Scheduling of Antagonist Cycles. AB - Antagonist cycles have an inherent issue of lack of flexibility. As a result where batching of cycles is desired, it is not the preferred protocol in ART cycles. There is also the limitation of ovarian response in antagonist cycle due to the size heterogenesities of antral follicles at the start of stimulation. Among the different options available, use of estrogen in the luteal phase of the preceding cycle has definitely shown benefits with regard to better control of cycle as well as synchronization of follicles available for stimulation. The article gives a detailed analysis of the different options available for timing the egg collection in antagonist cycles, the advantages and drawbacks, and the method of use of estrogen. Whereas in the majority of the trials where estrogen pretreatment was used, the goal of scheduling of egg collection was definitely achieved, increased duration and dose of gonadotropin stimulation were required. There was definite advantage of higher oocyte yield in these cycles. The possibility of premature LH rise later during stimulation and subsequent poor implantation in these cycles has to be further evaluated. Nevertheless, batching of patient friendly antagonist cycles can be effectively possible by use of precycle estrogen treatment. PMID- 27382227 TI - ThermiVa: The Revolutionary Technology for Vulvovaginal Rejuvenation and Noninvasive Management of Female SUI. AB - Addressing vaginal laxity, atrophic vaginitis, stress urinary incontinence (SUI), and different manifestations of sexual dysfunction has always been problematic due to women's traditional difficulty discussing these issues with doctors as well as the societal attitude of resignation toward these conditions. The recent rise of non-invasive feminine rejuvenation using energy-based modalities to vaginal tissue has its origins in aesthetic medicine. Transcutaneous temperature controlled radiofrequency therapy at the vulvovaginal region has shown promising results in giving a more youthful appearing vulva, restoration of vaginal elasticity and 'tightness', considerable improvement in SUI, reduction in overactive bladder symptoms, and reduction in sexual dysfunction. It is also emerging as the non-invasive treatment modality for mild to moderate SUI. It seems that the time has come, when women shall ever be grateful to their gynecologist for management of SUI with ThermiVa without an incision. PMID- 27382228 TI - From the Editor's desk. PMID- 27382229 TI - Poor ovarian reserve. AB - Poor ovarian reserve (POR) is an important limiting factor for the success of any treatment modality for infertility. It indicates a reduction in quantity and quality of oocytes in women of reproductive age group. It may be age related as seen in advanced years of reproductive life or may occur in young women due to diverse etiological factors. Evaluating ovarian reserve and individualizing the therapeutic strategies are very important for optimizing the success rate. Majority or women with POR need to undergo in vitro fertilization to achieve pregnancy. However, pregnancy rate remains low despite a plethora of interventions and is associated with high pregnancy loss. Early detection and active management are essential to minimize the need for egg donation in these women. PMID- 27382230 TI - Effective treatment protocol for poor ovarian response: A systematic review and meta-analysis. AB - Poor ovarian response represents an increasingly common problem. This systematic review was aimed to identify the most effective treatment protocol for poor response. We searched MEDLINE, EMBASE, and The Cochrane Library from 1980 to October 2015. Study quality assessment and meta-analyses were performed according to the Cochrane recommendations. We found 61 trials including 4997 cycles employing 10 management strategies. Most common strategy was the use of gonadotropin-releasing hormone antagonist (GnRHant), and was compared with GnRH agonist protocol (17 trials; n = 1696) for pituitary down-regulation which showed no significant difference in the outcome. Luteinizing hormone supplementation (eight trials, n = 847) showed no difference in the outcome. Growth hormone supplementation (seven trials; n = 251) showed significant improvement in clinical pregnancy rate (CPR) and live birth rate (LBR) with an odds ratio (OR) of 2.13 (95% CI 1.06-4.28) and 2.96 (95% CI 1.17-7.52). Testosterone supplementation (three trials; n = 225) significantly improved CPR (OR 2.4; 95% CI 1.16-5.04) and LBR (OR 2.18; 95% CI 1.01-4.68). Aromatase inhibitors (four trials; n = 223) and dehydroepiandrosterone supplementation (two trials; n = 57) had no effect on outcome. PMID- 27382231 TI - Postmortem sperm retrieval in context of developing countries of Indian subcontinent. AB - There was a request for postmortem sperm retrieval (PMSR) from the wife of a deceased, but we had to decline. We have no guideline in place for the procedure in such cases. When we explored the international scenario on the issue of PMSR, we found that most of the developed countries have their guidelines about it, whether to allow or not to. There is not guideline available in developing countries, as such, for the procedure and various medical, legal, and social issues related thereto. In this article, we have explored the status of postmortem retrieval and feasibility of the procedure in developing countries of Indian subcontinent. PMID- 27382232 TI - Association of tumor necrosis factor-alpha 308G/A polymorphism with recurrent miscarriages in women. AB - BACKGROUND: Recurrent miscarriage (RM) is the most common pregnancy loss in the first trimester affecting approximately 0.5-2% of women. It is a heterogeneous condition and remains an enigma as the underlying cause is still difficult to track down. AIM: This study was aimed to investigate the distribution of tumor necrosis factor-alpha (TNF-alpha) 308G/A polymorphism and its association with RM in females. The comparative picture was also demonstrated by comparing genotyping results with healthy control women having no history of miscarriage. METHODS: This clinical study was conducted among 115 women aged 21-44 years with history of recurrence of miscarriage. The samples were collected from women attending the outpatient departments of various hospitals, nursing homes, and infertility clinics of this region. In the present study, 111 fertile healthy women aged 24 46 years with at least one live birth and no history of miscarriage were also included. RESULTS: Mean age of women with RM was found to be 28 +/- 5.6 years by recall method, whereas it was found to be 30 +/- 7.4 in context to healthy women with no history of pregnancy loss. In the present study, 66% of women with RM had homozygous wild type genotype (GG) while 30% and 4% of women had heterozygous (GA) and homozygous mutant genotype (AA), respectively. Among control group, 79%, 16%, and 5% of women showed GG, GA, and AA genotype, respectively. CONCLUSION: The current study supports the concept of TNF-alpha 308G/A variant in particular with reproductive failure, GG and GA alleles showing 1-fold risk association with RM (odds ratio: 1.86 and 1.43, respectively). PMID- 27382233 TI - Pilot initiative in India to explore the gonadal function and fertility outcomes of a cohort of childhood cancer survivors. AB - CONTEXT: Steady improvement in childhood cancer outcomes has led to a growing number of survivors, many of who develop long-term sequelae. There is limited data about these sequelae (including those related to fertility) on childhood cancer survivors from India. AIMS: We undertook a prospective pilot study on childhood cancer survivors from India to assess their gonadal function and fertility. SUBJECTS AND METHODS: A pediatric oncologist and a reproductive medicine specialist assessed 21 childhood cancer survivors. The risk of infertility was established using disease and treatment variables. Current status of puberty, sexuality, and fertility were assessed using clinical and biochemical parameters. Outcomes were correlated with risk group of infertility. Information was also ascertained on counseling with regards to risk of infertility. RESULTS: The cohort included 21 survivors (71% males) with a median age of 18 years who were off treatment for a median age of 7 years. Ten (48%) survivors were at low risk for infertility, 9 (43%) at medium risk and 2 (9%) at high risk. Gonadal dysfunction was seen in 3 (14%) survivors: 0/10 (0%) low risk, 1/9 (11%) medium risk, and 2/2 (100%) high risk. None of the survivors, who are at high risk or medium risk of infertility, received any counseling before treatment. CONCLUSIONS: This prospective pilot study of a cohort of childhood cancer survivors from India demonstrates a deficiency in the information provided and counseling of patients/families at the time of diagnosis with regards to the risk of infertility. Fertility outcomes of childhood cancer survivors were congruent with recognized risk groups for infertility. Future action points have been identified. PMID- 27382234 TI - Preimplantation genetic screening for all 24 chromosomes by microarray comparative genomic hybridization significantly increases implantation rates and clinical pregnancy rates in patients undergoing in vitro fertilization with poor prognosis. AB - CONTEXT: A majority of human embryos produced in vitro are aneuploid, especially in couples undergoing in vitro fertilization (IVF) with poor prognosis. Preimplantation genetic screening (PGS) for all 24 chromosomes has the potential to select the most euploid embryos for transfer in such cases. AIM: To study the efficacy of PGS for all 24 chromosomes by microarray comparative genomic hybridization (array CGH) in Indian couples undergoing IVF cycles with poor prognosis. SETTINGS AND DESIGN: A retrospective, case-control study was undertaken in an institution-based tertiary care IVF center to compare the clinical outcomes of twenty patients, who underwent 21 PGS cycles with poor prognosis, with 128 non-PGS patients in the control group, with the same inclusion criterion as for the PGS group. MATERIALS AND METHODS: Single cells were obtained by laser-assisted embryo biopsy from day 3 embryos and subsequently analyzed by array CGH for all 24 chromosomes. Once the array CGH results were available on the morning of day 5, only chromosomally normal embryos that had progressed to blastocyst stage were transferred. RESULTS: The implantation rate and clinical pregnancy rate (PR) per transfer were found to be significantly higher in the PGS group than in the control group (63.2% vs. 26.2%, P = 0.001 and 73.3% vs. 36.7%, P = 0.006, respectively), while the multiple PRs sharply declined from 31.9% to 9.1% in the PGS group. CONCLUSIONS: In this pilot study, we have shown that PGS by array CGH can improve the clinical outcome in patients undergoing IVF with poor prognosis. PMID- 27382235 TI - Evaluation of dual trigger with gonadotropin-releasing hormone agonist and human chorionic gonadotropin in improving oocyte maturity rates: A prospective randomized study. AB - BACKGROUND: Mature oocytes are prerequisite for achieving the process of in vitro fertilization. Human chorionic gonadotropin (hCG) is the standard trigger used for stimulating ovulation but is associated with ovarian hyperstimulation syndrome (OHSS). Gonadotropin-releasing hormone agonist trigger achieves oocyte maturation and lowers the incidence of OHSS, but it has limitations of higher pregnancy loss rate and miscarriage rates. Coadministration of both hormones is found to improve the pregnancy rates and the number of mature oocytes retrieved. We aimed to assess if the dual trigger is better than the conventional hCG in triggering oocyte maturation. METHODOLOGY: The study included 76 female patients aged 24-43 years who were randomly divided into two groups with 38 patients in each arm. The study included patients with antimullerian hormone (AMH) <4 ng/ml, antral follicle counts (AFCs)/ovary <12. The study excluded high responders-AMH >4 ng/ml and AFC/ovary >12 to avoid OHSS risk with hCG trigger. RESULTS: The study showed statistically insignificant differences between dual group versus hCG group in terms of the number of oocytes retrieved (10.0 +/- 5.6 vs. 8.7 +/- 5.0; P = 0.2816), the number of mature oocytes recovered (8.4 +/- 5.0 vs. 7.2 +/- 4.0; P = 0.2588), fertilization rate (5.9 +/- 4.2 vs. 5.6 +/- 3.3; P = 0.7390), and the number of usable embryos on day 3 (4.0 +/- 3.0 vs. 4.0 +/- 2.4; P = 0.8991). CONCLUSION: The dual trigger is equivalent to hCG in triggering oocyte maturation. PMID- 27382236 TI - Effect of myomectomy on endometrial cavity: A prospective study of 51 cases. AB - CONTEXT: Fibroids are the most common tumors of the uterine cavity. Most of them are diagnosed during the reproductive age when the fertility is an important concern for the female. However, complications can occur after removal of fibroid (myomectomy) too for future pregnancy. Though myomectomy has been sighted as a cause of intrauterine adhesions data regarding the effect of myomectomy on endometrial cavity is lacking. AIMS: Evaluate the incidence of intrauterine adhesion formation after myomectomy and to identify the associated factors. MATERIALS AND METHODS: In this prospective observational study, hysteroscopy was done in 51 infertile patients who had undergone myomectomy 3 months before in a tertiary care center from 2012 to 2015. The presence of intrauterine adhesions noted on hysteroscopy was investigated on the basis of size, number, location and type of fibroid removed, along with intraoperative breach of the uterine cavity. STATISTICAL ANALYSIS: Chi-square test was used for the calculating significant difference in frequency of discrete variables in two groups. P < 0.05 was considered significant. RESULTS: Intrauterine adhesions were seen in 11 out of 51 (21.57%) cases. No significant relationship between intrauterine adhesions and type, size or number of fibroid was observed. No statistical difference in the rate of adhesion formation was seen irrespective of breach of the uterine cavity during myomectomy. CONCLUSION: Intrauterine adhesion formation after myomectomy is not related to the type of surgery or the nature of fibroid. However, in all cases desiring fertility postoperative hysteroscopy is highly recommended to diagnose and treat these adhesions early. PMID- 27382238 TI - Pregnancy at 65, risks and complications. AB - A 65-year-old postmenopausal pregnant woman was referred with antepartum hemorrhage at 29 weeks of gestation. Postadmission diagnosed with chronic hypertension, gestational diabetes mellitus, valvular heart disease, and placenta previa. Her pregnancy was terminated by cesarean delivery at 32 weeks as she had a bout of bleeding per vaginum. Most of the placenta was adherent with no plane of cleavage; therefore, cesarean hysterectomy was performed. Baby birth weight was 1650 g and was shifted to nursery for observation and mother needed Intensive Care Unit care postcesarean. On the 15(th) day, both healthy mother and baby were discharged. Although pregnancy is possible in postmenopausal women with hormone support but the incidence of complications remain very high. It raises a need for developing well-laid guidelines for performing in vitro fertilization in older age group women. PMID- 27382237 TI - Morphokinetic behavior of euploid and aneuploid embryos analyzed by time-lapse in embryoscope. AB - BACKGROUND: Embryonic aneuploidy may result in miscarriage, implantation failure, or birth defects. Thus, it is clinically necessary to avoid the selection of aneuploid embryos during in vitro fertilization treatment. AIM: The aim of this study was to identify the morphokinetic differences by analyzing the development of euploid and aneuploid embryos using a time-lapse technology. We also checked the accuracy of a previously described model for selection of euploid embryos based on morphokinetics in our study population. MATERIALS AND METHODS: It is a retrospective study of 29 cycles undergoing preimplantation genetic screening from October 2013 to April 2015 at our center. Of 253 embryos, 167 suitable for biopsy embryos were analyzed for their chromosomal status using array-comparative genome hybridization (CGH). The morphokinetic behavior of these embryos was further analyzed in embryoscope using time-lapse technology. RESULTS: Among the analyzed embryos, 41 had normal and 126 had abnormal chromosome content. No significant difference in morphokinetics was found between euploid and aneuploid embryos. The percentage of embryos with blastulation was similar in the euploid (65.85%, 27/41) and aneuploid (60.31%, 76/126) embryos (P = 0.76). Although hard to define, majority of the chromosomal defects might be due to meiotic errors. On applying embryo selection model from Basile et al., embryos falling within optimal ranges for time to division to 5 cells (t5), time period of the third cell cycle (CC3), and time from 2 cell division to 5 cell division (t5-t2) exhibited greater proportion of normal embryos than those falling outside the optimal ranges (28.6%, 25.9%, and 26.7% vs. 17.5%, 20.8%, and 14.3%). CONCLUSION: Keeping a track of time interval between two stages can help us recognize aneuploid embryos at an earlier stage and prevent their selection of transfer. However, it cannot be used as a substitute for array CGH to select euploid embryos for transfer. PMID- 27382239 TI - Successful birth of South India's first twins after preimplantation genetic screening of embryos. AB - We report the first documented successful birth of twins following preimplantation genetic screening (PGS) of cleavage stage embryos by array comparative genomic hybridization (CGH) technology, in South India. The case was a 28-year-old woman with the previous history of preclinical pregnancy and a miscarriage in two attempted in vitro fertilization cycles. Day 3 cleavage stage embryos were generated by conventional long protocol with the use of a gonadotropin-releasing hormone analog and a combination of recombinant folliculotropins and human menopausal gonadotropins. Intracytoplasmic sperm injection of oocytes thus obtained was performed, and 10 selected embryos underwent PGS using the array CGH technique. Two normal blastocysts were transferred to the patient, and she conceived twins. She delivered at 35 weeks of gestation by elective cesarean on November 19, 2014. She delivered a healthy male and female baby weighing 2.19 kg and 2.26 kg, respectively. Postnatal evaluation of babies was also normal, and the hospital course was uneventful. PGS has a definitive indication in assisted reproductive technology programs and can be utilized to improve pregnancy rates significantly. PMID- 27382240 TI - An eventful journey from menarche to successful motherhood. AB - Herlyn-Werner-Wunderlich syndrome is an uncommon variant of mullerian duct anomaly and the approach to its diagnosis requires a high index of suspicion and vigilant work up. Presented here is a case of a 26-year-old woman who had the aforementioned anomaly and was pursued for nearly 10 years to provide her with a fruitful obstetric outcome after having undergone Strassman's metroplasty at a young age of 15 years. PMID- 27382241 TI - A rare balanced nonrobertsonian translocation involving acrocentric chromosomes: Chromosome abnormality of t(13;15)(p11.2;q22.1). AB - BACKGROUND: Balanced non-robertsonian translocation (RT), involving acrocentric chromosomes, is a rare event and only a few cases are reported. Most of the RTs are balanced involving acrocentric chromosomes with the breakpoints (q10;q10). MATERIALS AND METHODS: Chromosome analysis was performed as per standard procedure - Giemsa-trypsin banding with 500 band resolution was analyzed for chromosome identification. RESULTS: In the present study, we report a rare balanced non-RTs involving chromosomes 13 and 15 with cytogenetic finding of 46, XX, t(13;15) (p11.2;q22.1). CONCLUSION: To the best of our knowledge, this is the first such report of an unusual non-RT of t(13:15) with (p11.2;q22.1) break points. PMID- 27382242 TI - Erratum: Microdeletion of Y chromosome as a cause of recurrent pregnancy loss. AB - [This corrects the article on p. 159 in vol. 8, PMID: 26538859.]. PMID- 27382243 TI - Joint Patch and Multi-label Learning for Facial Action Unit Detection. AB - The face is one of the most powerful channel of nonverbal communication. The most commonly used taxonomy to describe facial behaviour is the Facial Action Coding System (FACS). FACS segments the visible effects of facial muscle activation into 30+ action units (AUs). AUs, which may occur alone and in thousands of combinations, can describe nearly all-possible facial expressions. Most existing methods for automatic AU detection treat the problem using one-vs-all classifiers and fail to exploit dependencies among AU and facial features. We introduce joint patch and multi-label learning (JPML) to address these issues. JPML leverages group sparsity by selecting a sparse subset of facial patches while learning a multi-label classifier. In four of five comparisons on three diverse datasets, CK+, GFT, and BP4D, JPML produced the highest average F1 scores in comparison with state-of-the art. PMID- 27382244 TI - The Effect of Mechanical Vibration Stimulation of Perception Subthreshold on the Muscle Force and Muscle Reaction Time of Lower Leg. AB - The objective of this study is to investigate the effect of mechanical vibration stimulation on the muscle force and muscle reaction time of lower leg according to perception threshold and vibration frequency. A vibration stimulation with perception threshold intensity was applied on the Achilles tendon and tibialis anterior tendon. EMG measurement and analysis system were used to analyze the change of muscle force and muscle reaction time according to perception threshold and vibration frequency. A root-mean-square (RMS) value was extracted using analysis software and Maximum Voluntary Contraction (MVC) and Premotor Time (PMT) were analyzed. The measurement results showed that perception threshold was different from application sites of vibration frequency. Also, the muscle force and muscle reaction time showed difference according to the presence of vibration, frequency, and intensity. This result means that the vibration stimulation causes the change on the muscle force and muscle reaction time and affects the muscles of lower leg by the characteristics of vibration stimulation. PMID- 27382245 TI - The impact of a preloaded intraocular lens delivery system on operating room efficiency in routine cataract surgery. AB - PURPOSE: The aim of this study was to evaluate the operational impact of using preloaded intraocular lens (IOL) delivery systems compared with manually loaded IOL delivery processes during routine cataract surgeries. METHODS: Time and motion data, staff and surgery schedules, and cost accounting reports were collected across three sites located in the US, France, and Canada. Time and motion data were collected for manually loaded IOL processes and preloaded IOL delivery systems over four surgery days. Staff and surgery schedules and cost accounting reports were collected during the 2 months prior and after introduction of the preloaded IOL delivery system. RESULTS: The study included a total of 154 routine cataract surgeries across all three sites. Of these, 77 surgeries were performed using a preloaded IOL delivery system, and the remaining 77 surgeries were performed using a manual IOL delivery process. Across all three sites, use of the preloaded IOL delivery system significantly decreased mean total case time by 6.2%-12.0% (P<0.001 for data from Canada and the US and P<0.05 for data from France). Use of the preloaded delivery system also decreased surgeon lens time, surgeon delays, and eliminated lens touches during IOL preparation. CONCLUSION: Compared to a manual IOL delivery process, use of a preloaded IOL delivery system for cataract surgery reduced total case time, total surgeon lens time, surgeon delays, and eliminated IOL touches. The time savings provided by the preloaded IOL delivery system provide an opportunity for sites to improve routine cataract surgery throughput without impacting surgeon or staff capacity. PMID- 27382246 TI - Effect of prophylactic timolol 0.1% gel on intraocular pressure after an intravitreal injection of ranibizumab: a randomized study. AB - PURPOSE: The purpose of this study is to make a prospective evaluation of the effect of timolol 0.1% eye gel on short-term intraocular pressure (IOP) after an intravitreal injection (IVI) of ranibizumab. PARTICIPANTS AND METHODS: One hundred and fifty eyes of 150 IVI-naive patients with macular edema caused by various pathological conditions (age-related macular degeneration, central or branch retinal vein occlusion, and diabetic retinopathy) were scheduled to undergo an IVI of ranibizumab (0.5 mg/0.05 cc). The patients were randomly divided into three groups: 50 were not treated with timolol before the IVI (group 1); 50 received an instillation of timolol 0.1% eye gel the evening before the IVI (group 2); and 50 received an instillation of timolol 0.1% eye gel 2 hours before the IVI (group 3). The incidence of clinically significant intraocular hypertensive spikes (>25 mmHg and >40 mmHg) was then assessed. RESULTS: Our findings showed that mean IOP at baseline was significantly higher than at both 5 and 60 minutes after IVI (P<0.01). Spikes of >25 mmHg were recorded at either time in 27 patients (54%) in group 1, 23 patients (44%) in group 2, and 24 patients (48%) in group 3. None of the between-group differences were significant. Spikes of >40 mmHg (which were only detected 5 minutes after IVI) were recorded in nine (18%), eight (16%), and one patient (2%) in groups 1, 2, and 3, respectively. The only significant difference was between the control and group 3 (P=0.012). CONCLUSION: An increase in IOP after antivascular endothelial growth factor IVI is a frequent complication. The prophylactic use of timolol 0.1% gel effectively reduced the mean IOP when administered 2 hours before IVI and was also effective in preventing dangerous IOP spikes of >40 mmHg. It is therefore recommended before IVIs as a means of preventing emergency procedures and preserving the health of the optic nerve. PMID- 27382247 TI - A comparison of patient pain and visual outcome using topical anesthesia versus regional anesthesia during cataract surgery. AB - PURPOSE: The purpose of this study was to compare the level of patient pain during the phacoemulsification and implantation of foldable intraocular lenses while under topical, intracameral, or sub-Tenon lidocaine. PATIENTS AND METHODS: This was a retrospective study. Three hundred and one eyes subjected to cataract surgery were included in this study. All eyes underwent phacoemulsification surgery and intraocular lens implantation using topical, sub-Tenon, or intracameral anesthesia. The topical group received 4% lidocaine drops, and the intracameral group received a 0.1-0.2 cc infusion of 1% preservative-free lidocaine into the anterior chamber through the side port combined with topical drops of lidocaine. The sub-Tenon group received 2% lidocaine. Best-corrected visual acuity, corneal endothelial cell loss, and intraoperative pain level were evaluated. Pain level was assessed on a visual analog scale (range 0-2). RESULTS: There were no significant differences in visual outcome and corneal endothelial cell loss between the three groups. The mean pain score in the sub-Tenon group was significantly lower than that in the topical and intracameral groups (P=0.0009 and P=0.0055, respectively). In 250 eyes without high myopia (< -6D), there were no significant differences in mean pain score between the sub-Tenon and intracameral groups (P=0.1417). No additional anesthesia was required in all groups. CONCLUSION: Intracameral lidocaine provides sufficient pain suppressive effects in eyes without high myopia, while sub-Tenon anesthesia is better for cataract surgery in eyes with high myopia. PMID- 27382248 TI - Long-term follow-up of vitrectomy, with or without 360 degrees encircling buckle, for rhegmatogenous retinal detachment due to inferior retinal breaks. AB - OBJECTIVE: The aim of this study was to report and compare the anatomic and functional results of primary vitrectomy with and without 360 degrees encircling scleral buckle (SB) for the treatment of rhegmatogenous retinal detachment (RRD) due to inferior retinal break(s). BACKGROUND: A variety of options, including SB, pars plana vitrectomy (PPV) with or without SB, and pneumatic retinopexy have been described as methods to repair RRDs. The use of additional SB with vitrectomy for RRD associated with inferior breaks has been a recent controversy after the introduction of transconjunctival cannula systems. PATIENTS AND METHODS: A retrospective, interventional, comparative case study was performed. In this study, we reviewed 105 consecutive patients who underwent vitrectomy for primary RRD with inferior retinal break(s) at the vitreoretinal center, performed by a single surgeon. Ninety four patients (94 eyes) were followed up for at least 4 months after silicon oil removal (SOR), and were analyzed. They were divided into two groups: group I included 50 patients who underwent PPV alone + silicon oil (SO); and group II included 44 patients who underwent PPV with 360 degrees SB + SO. The essential parameters were single-operation success rate (SOSR) before SOR, incidence of retinal redetachment after SOR, and final visual acuity. RESULTS: SOSR was obtained in 89 eyes (47 [94%] in group I and 42 [95.5%] in group II). From overall 59 phakic retinal detachments (RDs), SOSR was obtained in 56 eyes (30 in group I [93.8%] and 26 in group II [96.3%]) while from overall 35 aphakic or pseudophakic RDs, SOSR was obtained in 33 eyes (17 in group I [94.4%] and 16 in group II [94.1%]). Retinal redetachments after SOR occurred in three patients in group I and two patients in group II. Visual acuity improvement was greater in group I than in group II before SOR. CONCLUSION: Both surgical procedures had similar reattachment rates. The addition of 360 degrees SB to PPV + SO might not have additional benefits in patients with RD due to inferior retinal break. PMID- 27382249 TI - Toric intraocular lenses for correction of astigmatism in keratoconus and after corneal surgery. AB - PURPOSE: To describe the results of cataract extraction with toric intraocular lens (IOL) implantation in patients with preexisting astigmatism from three corneal conditions (keratoconus, postkeratoplasty, and postpterygium surgery). METHODS: Cataract patients with topographically stable, fairly regular (although sometimes very high) corneal astigmatism underwent phacoemulsification with implantation of a toric IOL (Zeiss AT TORBI 709, Alcon Acrysof IQ toric SN6AT, AMO Tecnis ZCT). Postoperative astigmatism and refractive outcomes, as well as visual acuities, vector reduction, and complications were recorded for all eyes. RESULTS: This study evaluated 17 eyes of 16 patients with a mean age of 60 years at the time of surgery. Mean follow-up in this study was 12 months. The corrected distance Snellen visual acuity (with spectacles or contact lenses) 12 months postoperatively was 20/32 or better in 82% of eyes. The mean corneal astigmatism was 6.7 diopters (D) preoperatively, and 1.5 D of refractive cylinder at 1-year follow-up. No vision-compromising intra- or postoperative complications occurred and decentration or off-axis alignment of toric IOLs were not observed. CONCLUSION: Phacoemulsification with toric IOL implantation was a safe and effective procedure in the three mentioned corneal conditions. Patient selection, counseling, and IOL placement with optimal astigmatism correction are crucial. PMID- 27382250 TI - Twelve-month outcomes in patients with retinal vein occlusion treated with low frequency intravitreal ranibizumab. AB - PURPOSE: The purpose of this study was to determine the clinical efficacy of low frequency intravitreal ranibizumab to treat macular edema due to retinal vein occlusion (RVO). PATIENTS AND METHODS: This was a retrospective examination of cases that received intravitreal ranibizumab for untreated RVO over a period of 12 months. Instead of the conventional three monthly injections, injections were given once during the introductory period. If the recurrence of macular edema was diagnosed during the monthly visit, additional injections were given as needed. There were 21 eyes of 21 patients with branch RVO (BRVO) and ten eyes of ten patients with central RVO (CRVO). The parameters examined included the number of injections over the 12-month period, improvements in best-corrected visual acuity (BCVA), and the central macular thickness (CMT). For BRVO, preinjection parameters that had an effect on the prognosis of BCVA after the 12-month period were also examined. RESULTS: The total mean number of injections over the 12 month period was 3.4 for CRVO and 2.1 for BRVO. For CRVO, the BCVA in log minimum angular resolution changed from a preinjection value of 0.80 to 0.55 at 12 months. For BRVO, the change was from 0.51 to 0.30. For all diseases, BCVA improved after 12 months compared with the preinjection values (P<0.05). There was improvement in the CMT, and the CRVO changed from 765.0 MUm at preinjection to 253.5 MUm 12 months later. BRVO changed from 524.1 to 250.1 MUm, and pre injection BCVA was associated with a prognosis of visual acuity after 12 months of the initial injection (P=0.0485). CONCLUSION: Even with a low number of injections during the introductory period, there were still improvements in both visual acuity and CMT in RVO patients after 12 months, indicating that it was an effective treatment. PMID- 27382251 TI - Double-blind, randomized, double-dummy clinical trial comparing the efficacy of ketorolac trometamol and naproxen for acute low back pain. AB - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common type of medication used in the treatment of acute pain. Ketorolac trometamol (KT) is a nonnarcotic, peripherally acting nonsteroidal anti-inflammatory drug with analgesic effects comparable to certain opioids. OBJECTIVE: The aim of this study was to compare the efficacy of KT and naproxen (NA) in the treatment of acute low back pain (LBP) of moderate-to-severe intensity. PATIENTS AND METHODS: In this 10 day, Phase III, randomized, double-blind, double-dummy, noninferiority trial, participants with acute LBP of moderate-to-severe intensity as determined through a visual analog scale (VAS) were randomly assigned in a 1:1 ratio to receive sublingual KT 10 mg three times daily or oral NA 250 mg three times daily. From the second to the fifth day of treatment, if patient had VAS >40 mm, increased dosage to four times per day was allowed. The primary end point was the reduction in LBP as measured by VAS. We also performed a post hoc superiority analysis. RESULTS: KT was not inferior to NA for the reduction in LBP over 5 days of use as measured by VAS scores (P=0.608 for equality of variance; P=0.321 for equality of means) and by the Roland-Morris Disability Questionnaire (P=0.180 for equality of variance test; P=0.446 for equality of means) using 95% confidence intervals. The percentage of participants with improved pain relief 60 minutes after receiving the first dose was higher in the KT group (24.2%) than in the NA group (6.5%; P=0.049). The most common adverse effects were heartburn, nausea, and vomiting. CONCLUSION: KT is not inferior in efficacy and delivers faster pain relief than NA. PMID- 27382252 TI - MART-10, a newly synthesized vitamin D analog, represses metastatic potential of head and neck squamous carcinoma cells. AB - Even with multidisciplinary treatment, the prognosis and quality of life of patients diagnosed with head and neck squamous cell carcinoma (HNSCC) are still not satisfactory. Previously, 19-Nor-2alpha-(3-hydroxypropyl)-1alpha,25(OH)2D3 (MART-10), the new brand 1alpha,25(OH)2D3 analog, has been demonstrated to be an effective drug to inhibit HNSCC growth in vitro. Since most cancer patients die of metastasis, in this study, the antimetastatic effect of MART-10 on HNSCC was investigated. Our results reveal that both 1alpha,25(OH)2D3 and MART-10 effectively repressed the migration and invasion of HNSCC cells, with MART-10 being much more potent than 1alpha,25(OH)2D3. The antimetastatic effect of 1alpha,25(OH)2D3 and MART-10 was mediated by attenuation of epithelial mesenchymal transition (EMT), which was supported by the finding that the expression of EMT-inducing transcriptional factors, Sail and Twist, was inhibited by 1alpha,25(OH)2D3 and MART-10. The upregulation of E-cadherin and downregulation of N-cadherin in FaDu cells induced by both drugs further confirmed the repression of EMT. In addition, 1alpha,25(OH)2D3 and MART-10 treatment inhibited intracellular MMP-9 expression and extracellular MMP activity in FaDu cells. Collectively, our results suggest that the less-calcemia 1alpha,25(OH)2D3 analog, MART-10, is a promising drug for HNSCC treatment. Further clinical studies are warranted. PMID- 27382253 TI - The aqueous extract of Chinese medicinal herb Brucea javanica suppresses the growth of human liver cancer and the derived stem-like cells by apoptosis. AB - Being effective and relatively safe, the traditional Chinese medicinal herb Brucea javanica (BJ) has been valuable in curing patients in East Asia and its nearby regions for years. Recent reports suggested that the medicinal herb possesses broad antitumor activity against various cancer cells. This study evaluated whether low concentrations of BJ aqueous extract inhibited the growth of liver cancer cells. Experiments including flow cytometry and Western blot analysis established the development of apoptotic cell death after treatment. Further experiments evaluated the growth of the enriched spheroids. BJ not only reduced the expression of stem cell markers but also eliminated tumor spheroids by apoptotic death. The findings suggest BJ is a promising supplement to the current therapy regimen and highlight the opportunity of BJ as a practical avenue to suppress the growth of the stem cells in liver cancer. PMID- 27382254 TI - Position and enforcement practice of the People's Republic of China's pharmaceutical data exclusivity protection. AB - The concept of pharmaceutical data exclusivity protection comes from the West. The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) establishes the basic rules for pharmaceutical data exclusivity protection. People's Republic of China's domestic law is consistent with the TRIPS agreement. In the drug registration approval process of the People's Republic of China's Drug Supervision Department, pharmaceutical data exclusivity protection has encountered some problems, including data authentication, exclusive rights to data, number of drugs requiring data to be submitted, and drug costs. In view of the long-term interests of the People's Republic of China's pharmaceutical industry and intellectual property protection trends, there are a lot of difficulties in the enforcement of pharmaceutical data exclusivity protection law that need to be overcome. Some measures can be taken, such as establishing a shorter data exclusivity protection period, only protecting the data submitted and relied on in the People's Republic of China, only protecting the drugs that use new chemical components, allowing application and necessary research before the expiry of pharmaceutical data exclusivity protection period of generic drugs. PMID- 27382255 TI - A novel pH-enzyme-dependent mesalamine colon-specific delivery system. AB - The aim of the present study was to design a new pH-enzyme double-dependent mesalamine colon-specific delivery system. The drug release behaviors in vitro and pharmacokinetics and biodistribution in vivo were further evaluated. The mean particle diameters of mesalamine-coated microparticles were 312.2 um. In vitro, a small amount of mesalamine was released in HCl at a pH of 1.2 and PBS medium at a pH of 7.4 for 5 hours, and 71% of the entrapped mesalamine was further released during the subsequent 20 hours of incubation. A greater area under the plasma concentration-time curve (AUC)0-t was obtained for the coated microparticles (1.9 fold) compared to the suspensions group, which indicated that the encapsulated mesalamine had mostly been absorbed in rats over the period of 12 hours. The AUC0 t of the coated microparticles in colon was 2.63-fold higher compared to the suspensions (P<0.05). Hence, mesalamine-coated microparticles are considered to maintain the drug concentration within target ranges for a long period of time. PMID- 27382256 TI - Enhanced oral bioavailability of acetylpuerarin by poly(lactide-co-glycolide) nanoparticles optimized using uniform design combined with response surface methodology. AB - Acetylpuerarin (AP), an acetylated derivative of puerarin, shows brain-protective effects in animals. However, AP has low oral bioavailability because of its poor water solubility. The objective of this study was to design and develop poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) to enhance the oral bioavailability of AP. The NPs were prepared using a solvent diffusion method optimized via uniform design (UD) combined with response surface methodology (RSM) and characterized by their morphology, particle size, zeta (zeta) potential, encapsulation efficiency (EE), drug loading (DL), and in vitro drug release. A pharmacokinetic study was conducted in Wistar rats administered a single oral dose of 30 mg/kg AP. The optimized NPs were spherical and uniform in shape, with an average particle size of 145.0 nm, a polydispersity index (PI) of 0.153, and a zeta-potential of -14.81 mV. The release of AP from the PLGA NPs showed an initial burst release followed by a sustained release, following Higuchi's model. The EE and DL determined in the experiments were 90.51% and 17.07%, respectively. The area under the plasma concentration-time curve (AUC0 infinity) of AP-PLGA-NPs was 6,175.66+/-350.31 h ng/mL, which was 2.75 times greater than that obtained from an AP suspension. This study showed that PLGA NPs can significantly enhance the oral bioavailability of AP. PMID- 27382257 TI - Fondaparinux vs warfarin for the treatment of unsuspected pulmonary embolism in cancer patients. AB - INTRODUCTION: In cancer patients, the chest computer tomography (CT) can be used to identify asymptomatic pulmonary embolism (APE). In most cases, these patients are treated with anticoagulant drugs for at least 3 months. The American College of Physicians recommend treatment of these patients as patients with symptomatic pulmonary embolism. In this study, we evaluated and compared the efficacy and safety of fondaparinux vs warfarin in the prevention of unsuspected pulmonary embolism in patients with active cancer. MATERIALS AND METHODS: A prospective and parallel group study was performed on 64 cancer patients (29 males and 35 females) with APE. A multidetector CT angiography with high spatial and temporal resolution and quality of arterial opacification was used to make the diagnosis. Lung scintigraphy was reserved to selected patients only. Patients were randomized to either the warfarin (Group A) or the fondaparinux (Group B) for 90 days. The first end point of efficacy was the persistence, reduction, or disappearance of thrombosis after 90 days. The second end point was the reappearance of thrombosis after 1 year. The first end point of safety was the development of major bleeding. RESULTS: We enrolled 32 patients into each treatment group. We reached the first end point of efficacy and safety in Group B which showed that fondaparinux was able to induce the disappearance of thrombotic pulmonary with a lower incidence of major bleeding events compared with warfarin. No difference in the secondary end point was recorded. CONCLUSION: We suggest that the treatment of cancer patients with APE can be oriented with the administration of a standard dose of fondaparinux until the next CT lung control (3 months). However, the lack of a randomized clinical trial, including a larger patient cohort, does not allow formulation of final recommendations in these patients. A broader study would be desirable, involving a larger number of patients and a longer follow-up period. PMID- 27382258 TI - Patients' and rheumatologists' preferences for the attributes of biological agents used in the treatment of rheumatic diseases in Spain. AB - PURPOSE: To define importance values assigned to attributes of biological agents (BAs) by Spanish patients with rheumatic diseases (rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis) and rheumatologists. PATIENTS AND METHODS: This was an observational, cross-sectional design based upon a rank based full-profile conjoint analysis. A literature review and four focus groups were undertaken to identify attributes and levels. An orthogonal matrix, combining the selected levels of attributes, was used to define scenarios. Participants ranked eight scenarios from 1 (most preferred) to 8 (least preferred). The relative importance (RI) of attributes was calculated. Multivariate regression analysis was performed to identify the characteristics that influenced the values of RI. A total of 488 patients (male 50.9%, mean age 50.6 [standard deviation {SD} 12.06] years, rheumatoid arthritis 33.8%, ankylosing spondylitis 32.4%, psoriatic arthritis 33.8%; mean time since diagnosis 12.6 [SD 8.2] years) and 136 rheumatologists (male 50.4%, mean age 46.4 [SD 9.1] years, mean time of practice 16.7 [SD 8.8] years) participated. RESULTS: The ideal BAs for patients and physicians, respectively, should allow pain relief and improvement of functional capacity (RI 39% and 44.7%), with low risk of adverse events (RI 24.9% and 30.5%), a long time prior to perceiving the need for a new dose (RI 16.4% and 12.4%), and self-administration at home (RI 19.7% and 12.5%), as identified through their preferences. CONCLUSION: Although efficacy and safety are paramount for patients and rheumatologists to make a choice regarding BAs, the need for a low frequency of administration and the administration method also play a role as preference attributes for BAs. PMID- 27382259 TI - Drugs under preclinical and clinical study for treatment of acute and chronic lymphoblastic leukemia. AB - Targeted therapy has modernized the treatment of both chronic and acute lymphoblastic leukemia. The introduction of monoclonal antibodies and combinational drugs has increased the survival rate of patients. Preclinical studies with various agents have resulted in positive outputs with Phase III trial drugs and monoclonal antibodies entering clinical trials. Most of the monoclonal antibodies target the CD20 and CD22 receptors. This has led to the approval of a few of these drugs by the US Food and Drug Administration. This review focuses on the drugs under preclinical and clinical study in the ongoing efforts for treatment of acute and chronic lymphoblastic leukemia. PMID- 27382260 TI - Persistence and compliance with newly initiated antihypertensive drug treatment in patients with chronic kidney disease. AB - BACKGROUND: Patients with chronic kidney disease initiating an antihypertensive drug (AH) treatment must persist and comply with it to slow disease progression and benefit from the reduction of cardiovascular morbidity and mortality. OBJECTIVES: This study evaluates the persistence and compliance with AH treatment and identifies the associated factors among chronic kidney disease patients who initiated AH treatment. METHODS: A population-based cohort study using Quebec administrative data was conducted. Patients who still take any AH 1 year after initiation were considered persistent. Of these patients, those who had >=80% of days covered with an AH in the year after initiation were considered compliant. Factors associated with persistence and compliance were identified using a modified Poisson regression. RESULTS: Of the 7,119 eligible patients, 78.8% were persistent, 87.7% of whom were compliant with their AH treatment. Compared with patients on diuretic monotherapy, those who initially used angiotensin-converting enzyme inhibitor monotherapy, angiotensin II receptor blocker monotherapy, calcium channel blocker monotherapy, beta-blocker monotherapy, or multidrug therapy were more likely to be persistent. In contrast, individuals who visited their physicians >=17 times were less likely to be persistent than those who visited between 0 and 8 times. The patients who were more likely to be compliant had initially used an angiotensin-converting enzyme inhibitor, beta-blocker, calcium channel blocker, or multitherapy as opposed to a diuretic. CONCLUSION: A year after initiating AH treatment, nearly a third of chronic kidney disease patients were either not taking an AH or had not been compliant. Factors associated with persistence and compliance could help identify patients who need help in managing their AH treatment. PMID- 27382261 TI - Prevalence and severity of pain in adult end-stage renal disease patients on chronic intermittent hemodialysis: a systematic review. AB - OBJECTIVES: Understanding the epidemiology of pain in patients on hemodialysis (HD) is crucial for further improvement in managing pain. The aim of this study was to systematically review available evidence on the prevalence and severity of pain in adult end-stage renal disease patients on chronic intermittent HD. MATERIALS AND METHODS: We carried out a systematic review of the literature and developed a comprehensive search strategy based on search terms on pain and HD. We searched the databases MEDLINE, Scopus, PsycINFO, and CINAHL from the earliest date of each database to July 24, 2014. Manuscripts in all languages were taken into consideration. Two authors performed each step independently, and all disagreements were resolved after discussion with the third author. The quality of studies was estimated using the STROBE checklist and Cochrane risk-of-bias tool. RESULTS: We included 52 studies with 6,917 participants. The prevalence of acute and chronic pain in HD patients was up to 82% and 92%, respectively. A considerable number of patients suffered from severe pain. Various locations and causes of pain were described, with most of the studies reporting pain in general, pain related to arteriovenous access, headache, and musculoskeletal pain. CONCLUSION: The findings of this systematic review indicate high prevalence of pain in HD patients and considerable gaps and limitations in the available evidence. Pain in this population should be recognized as a considerable health concern, and the nephrology community should promote pain management in HD patients as a clinical and research priority to improve patients' quality of life and pain-related disability. PMID- 27382262 TI - Efficacies of globus pallidus stimulation and subthalamic nucleus stimulation for advanced Parkinson's disease: a meta-analysis of randomized controlled trials. AB - OBJECTIVES: Deep brain stimulation (DBS) is the surgical procedure for patients with advanced Parkinson's disease. Globus pallidus internus (GPi) and subthalamic nucleus (STN) are the most targeted locations for the procedure. To investigate the variable efficiencies for the two different locations, we conducted a meta analysis to compare both stimulation sites. MATERIALS AND METHODS: A systematic search was performed in PubMed, Embase, and the Cochrane Library databases. Randomized controlled trials comparing the efficacies of GPi and STN DBS were included. Clinical outcomes of motor function, nonmotor function, and quality of life (QOL) were collected for the meta-analysis. RESULTS: Ten eligible trials with 1,034 patients were included in the analysis. Unified Parkinson's disease rating scale III (UPDRS-III) scores were collected at 6, 12, and 24 months postsurgery separately to assess the motor function of the patients. A statistically significant effect in favor of the GPi DBS was obtained in the off medication/on-stimulation phase of UPDRS-III at 12 months (mean difference [MD] =6.87, 95% confidence interval [95% CI]: 3.00-10.74, P=0.57, I (2)=0%). However, GPi DBS showed an opposite result at 24 months (MD =-2.46, 95% CI: -4.91 to 0.02, P=0.05, I (2)=0%). In the on-medication/on-stimulation phase, GPi DBS obtained a worse outcome compared with STN DBS (MD =-2.90, 95% CI: -5.71 to 0.09, P=0.05, I (2)=0%). Compared with STN DBS, increased dosage of levodopa equivalent doses was needed in GPi DBS (standardized MD =0.60, 95% CI: 0.46-0.74, P<0.00001, I (2)=24%). Meanwhile, Beck Depression Inventory II scores demonstrated that STN has a better performance (standardized MD =-0.31, 95% CI: 0.51 to -0.12, P=0.002, I (2)=0%). As for neurocognitive phase postsurgery, GPi DBS showed better performance in three of the nine tests, especially in verbal fluency. Use of GPi DBS was associated with a greater effect in eight of the nine subscales of QOL. CONCLUSION: GPi and STN DBS significantly improve advanced Parkinson's patients' symptoms, functionality, and QOL. Variable therapeutic efficiencies were observed in both procedures, GPi and STN DBS. GPi DBS allowed greater recovery of verbal fluency and provided greater relief of depression symptoms. Better QOL was also obtained using GPi DBS. Meanwhile, GPi DBS was also associated with increased dosage of levodopa equivalent doses. The question regarding which target is superior remained open for discussion. An understanding of the target selection still depends on individual symptoms, neurocognitive/mood status, therapeutic goals of DBS (eg, levodopa reduction), and surgical expertise. PMID- 27382263 TI - Lifestyle and lifestyle-related comorbidities independently associated with colorectal adenoma recurrence in elderly Chinese people. AB - OBJECTIVE: The purpose of this study was to determine the lifestyle and lifestyle related comorbidities independently associated with colorectal adenoma (CRA) recurrence in elderly Chinese people. METHODS: During the 5-year follow-up after the initial colonoscopy, participants aged >60 years with the diagnosis and removal of CRA underwent a complete surveillance colonoscopy, and 152 participants with CRA recurrence plus 152 participants free of recurrence were included in this analysis. RESULTS: Participants with CRA recurrence were more likely to consume less vegetables and fruits, and more red meats compared with the control group (P<0.05 for all). Lifestyle-related comorbidities, including hypertension and nonalcoholic fatty liver disease (NAFLD), were more common in participants with CRA recurrence than in the control group (P<0.05 for all). In the multivariate analysis, pack-years of smoking were independently associated with an increased CRA recurrence (odds ratio [OR]: 1.03; P<0.05). Eating less vegetables (OR: 099; P<0.05) and fruits (OR: 0.98; P<0.05) was identified as a statistically independent factor influencing CRA recurrence, as was eating more red meats (OR: 1.01; P<0.05). Hypertension was also found to be a factor independently associated with an increased CRA recurrence (OR: 2.44; P<0.05). NAFLD had an independent association, with an increased CRA recurrence (OR: 3.43; P<0.05). CONCLUSION: Smoking cigarettes, high consumption of red meats, low intake of fruits and vegetables, and the presence of hypertension and NAFLD were independently associated with an increased CRA recurrence in elderly Chinese people. This conclusion helps elderly Chinese people to make effective behavioral changes, such as smoking cessation, substitution of fruits and vegetables for red meats, and timely treatment of hypertension and NAFLD, to reduce CRA recurrence and colorectal cancer risk. PMID- 27382264 TI - The Home Independence Program with non-health professionals as care managers: an evaluation. AB - The Home Independence Program (HIP), an Australian restorative home care/reablement service for older adults, has been shown to be effective in reducing functional dependency and increasing functional mobility, confidence in everyday activities, and quality of life. These gains were found to translate into a reduced need for ongoing care services and reduced health and aged care costs over time. Despite these positive outcomes, few Australian home care agencies have adopted the service model - a key reason being that few Australian providers employ health professionals, who act as care managers under the HIP service model. A call for proposals from Health Workforce Australia for projects to expand the scope of practice of health/aged care staff then provided the opportunity to develop, implement, and evaluate a service delivery model, in which nonprofessionals replaced the health professionals as Care Managers in the HIP service. Seventy older people who received the HIP Coordinator (HIPC) service participated in the outcomes evaluation. On a range of personal outcome measures, the group showed statistically significant improvement at 3 and 12 months compared to baseline. On each outcome, the improvement observed was larger than that observed in a previous trial in which the service was delivered by health professionals. However, differences in the timing of data collection between the two studies mean that a direct comparison cannot be made. Clients in both studies showed a similarly reduced need for ongoing home care services at both follow-up points. The outcomes achieved by HIPC, with non-health professionals as Care Managers, were positive and can be considered to compare favorably with the outcomes achieved in HIP when health professionals take the Care Manager role. These findings will be of interest to managers of home care services and to policy makers interested in reducing the long-term care needs of older community dwelling individuals. PMID- 27382265 TI - Inappropriate prescribing of antithrombotic therapy in Ethiopian elderly population using updated 2015 STOPP/START criteria: a cross-sectional study. AB - BACKGROUND: Inappropriate use of antiplatelets and anticoagulants among elderly patients increases the risk of adverse outcomes. The aim of this study was to assess the prevalence of inappropriate prescribing of antithrombotic therapy in hospitalized elderly patients. METHODS: A retrospective cross-sectional, single center study was conducted at the Gondar University Hospital. A total of 156 hospitalized elderly patients fulfilling the inclusion/exclusion criteria were included in the study. The Screening Tool for Older Person's Prescription/Screening Tool to Alert doctors to Right Treatment criteria version 2 were applied to patients' data to identify the total number of inappropriate prescribing (IPs) including potentially inappropriate medications and potential prescribing omissions. RESULTS: A total of 70 IPs were identified in 156 patients who met the inclusion criteria. Of these, 36 (51.4%) were identified as potentially inappropriate medications by the Screening Tool for Older Person's Prescription criteria. The prevalence of IP per patient indicated that 58 of the 156 (37.2%) patients were exposed to at least one IP. Of these, 32 (55.2%) had at least one potentially inappropriate medication and 33 (56.9%) had at least one potential prescribing omission. Patients hospitalized due to venous thromboembolism (adjusted odds ratio [AOR] =29.87, 95% confidence interval [CI], 1.26-708.6), stroke (AOR =7.74, 95% CI, 1.27-47.29), or acute coronary syndrome (AOR =13.48, 95% CI, 1.4-129.1) were less likely to be exposed to an IP. An increase in Charlson comorbidity index score was associated with increased IP exposure (AOR =0.60, 95% CI, 0.39-0.945). IPs were about six times more likely to absent in patients prescribed with antiplatelet only therapy (AOR =6.23, 95% CI, 1.90-20.37) than those receiving any other groups of antithrombotics. CONCLUSION: IPs are less common in elderly patients primarily admitted due to venous thromboembolism, stroke, and acute coronary syndrome, and those elderly patients prescribed with only antiplatelet. Patients with higher Charlson comorbidity index were, however, associated with increased IPs exposure. Our study may guide further research to reduce high-risk prescription of antithrombotics in the elderly. PMID- 27382266 TI - Prediction of critical illness in elderly outpatients using elder risk assessment: a population-based study. AB - RATIONALE: Identifying patients at high risk of critical illness is necessary for the development and testing of strategies to prevent critical illness. The aim of this study was to determine the relationship between high elder risk assessment (ERA) score and critical illness requiring intensive care and to see if the ERA can be used as a prediction tool to identify elderly patients at the primary care visit who are at high risk of critical illness. METHODS: A population-based historical cohort study was conducted in elderly patients (age >65 years) identified at the time of primary care visit in Rochester, MN, USA. Predictors including age, previous hospital days, and comorbid health conditions were identified from routine administrative data available in the electronic medical record. The main outcome was critical illness, defined as sepsis, need for mechanical ventilation, or death within 2 years of initial visit. Patients with an ERA score of 16 were considered to be at high risk. The discrimination of the ERA score was assessed using area under the receiver operating characteristic curve. RESULTS: Of the 13,457 eligible patients, 9,872 gave consent for medical record review and had full information on intensive care unit utilization. The mean age was 75.8 years (standard deviation +/-7.6 years), and 58% were female, 94% were Caucasian, 62% were married, and 13% were living in nursing homes. In the overall group, 417 patients (4.2%) suffered from critical illness. In the 1,134 patients with ERA >16, 154 (14%) suffered from critical illness. An ERA score >=16 predicted critical illness (odds ratio 6.35; 95% confidence interval 3.51-11.48). The area under the receiver operating characteristic curve was 0.75, which indicated good discrimination. CONCLUSION: A simple model based on easily obtainable administrative data predicted critical illness in the next 2 years in elderly outpatients with up to 14% of the highest risk population suffering from critical illness. This model can facilitate efficient enrollment of patients into clinical programs such as care transition programs and studies aimed at the prevention of critical illness. It also can serve as a reminder to initiate advance care planning for high-risk elderly patients. External validation of this tool in different populations may enhance its generalizability. PMID- 27382267 TI - Glucosamine-containing supplement improves locomotor functions in subjects with knee pain - a pilot study of gait analysis. AB - BACKGROUND: Previously, we demonstrated that glucosamine-containing supplementation was effective for improving locomotor functions, especially walking speed. However, the biomechanical mechanism of efficacy has not been elucidated. This study aimed to address this challenge in subjects with knee pain, using a motion capture system. METHODS: An open label study was conducted in 30 Japanese subjects with knee pain. The subjects were administered a daily supplement containing 1,200 mg of glucosamine hydrochloride, 60 mg of chondroitin sulfate, 45 mg of type II collagen peptides, 90 mg of quercetin glycosides, 10 mg of imidazole peptides, 1 mg of proteoglycan, and 5 MUg of vitamin D (GCQID). The intervention continued for 16 weeks. Efficacy for locomotor functions involving the knee joint was evaluated mainly using the Japanese Knee Osteoarthritis Measure (JKOM) and the 5-question Geriatric Locomotive Function Scale (GLFS-5). To examine the biomechanical mechanism of efficacy for locomotor functions, motions of subjects in a normal walking state were captured. Gait analysis was conducted and efficacy for gait parameters such as normal walking speed, stride length, cadence, and angle of soles was evaluated. RESULTS: GCQID significantly improved total scores on the JKOM and GLFS-5. In gait analysis, normal walking speed, stride length, and angle of soles at the end of the stance phase were all significantly increased, but cadence did not change significantly during the intervention period. There were significant intercorrelations of changes in normal walking speed, stride length, and angle of soles at the end of the stance phase, and between changes in stride length and total JKOM score. CONCLUSION: A GCQID supplement may increase walking speed through increased stride length and angle of kicking from the ground during steps, which might be mainly associated with alleviated knee pain. PMID- 27382268 TI - Methods to reduce prescribing errors in elderly patients with multimorbidity. AB - The global population of multimorbid older people is growing steadily. Multimorbidity is the principal cause of complex polypharmacy, which in turn is the prime risk factor for inappropriate prescribing and adverse drug reactions and events. Those who prescribe for older frailer multimorbid people are particularly prone to committing prescribing errors of various kinds. The causes of prescribing errors in this patient population are multifaceted and complex, including prescribers' lack of knowledge of aging physiology, geriatric medicine, and geriatric pharmacotherapy, overprescribing that frequently leads to major polypharmacy, inappropriate prescribing, and inappropriate drug omission. This review examines the various ways of minimizing prescribing errors in multimorbid older people. The role of education in physician prescribers and clinical pharmacists, the use of implicit and explicit prescribing criteria designed to improve medication appropriateness in older people, and the application of information and communication-technology systems to minimize errors are discussed in detail. Although evidence to support any single intervention to prevent prescribing errors in multimorbid elderly people is inconclusive or lacking, published data support focused prescriber education in geriatric pharmacotherapy, routine application of STOPP/START (screening tool of older people's prescriptions/screening tool to alert to right treatment) criteria for potentially inappropriate prescribing, electronic prescribing, and close liaison between clinical pharmacists and physicians in relation to structured medication review and reconciliation. Carrying out a structured medication review aimed at optimizing pharmacotherapy in this vulnerable patient population presents a major challenge. Another challenge is to design, build, validate, and test by clinical trials suitably versatile and efficient software engines that can reliably and swiftly perform complex medication reviews in older multimorbid people. The European Union-funded SENATOR and OPERAM clinical trials commencing in 2016 will examine the impact of customized software engines in reducing medication-related morbidity, avoidable excess cost, and rehospitalization in older multimorbid people. PMID- 27382269 TI - Chronic bronchitis is an independently associated factor for more symptom and high-risk groups. AB - BACKGROUND: The chronic bronchitis (CB) phenotype has been associated with poor quality of life and an increased risk of disease in patients with COPD. However, little information exists regarding the relationship between the CB phenotype and the COPD assessment test (CAT) score. The goal of this study was to reveal the different pattern of CAT scores between CB and non-CB patients. Moreover, we aimed to investigate whether the CB phenotype is an independently associated factor for more symptom and high-risk groups. METHODS: Data were obtained from the Korea COPD Subgroup Study cohort recruited from 46 centers in South Korea since April 2012. CB patients were defined as having a chronic cough and sputum for 3 months per year, for a period of 2 consecutive years. We investigated the pattern of CAT and subquestionnaire scores between CB and non-CB patients. We also analyzed the proportion of CB phenotypes in each Global initiative for chronic Obstructive Lung Disease (GOLD) stage. Finally, we performed a logistic regression analysis to identify whether the CB phenotype was an independently associated factor for more symptom and high-risk groups. RESULTS: Of the 1,106 study patients, 11.5% of patients were found to have a CB phenotype. CB phenotypes were most common in GOLD III (GOLD 2006) and GOLD D (GOLD 2015) stages. CAT scores were significantly higher in CB patients not only in terms of the total score but also for each subquestionnaire. Logistic regression revealed that the CB phenotype is an independently associated factor for more symptom and high-risk groups. CONCLUSION: The present study revealed that CB patients have higher CAT scores and subquestionnaire results compared to non-CB patients. Additionally, we demonstrated that the CB phenotype is an independently associated factor for both more symptom and high-risk groups. PMID- 27382270 TI - The impact of coping on the somatic and mental status of patients with COPD: a cross-sectional study. AB - BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is one of the most debilitating somatic diseases, having anxiety and depression frequently as comorbidities. The coping style, the way in which the subject manages to control the difficult and stressful situations of life, can influence its evolution and also the existence of the comorbidities. In this study, coping styles in a group of subjects with COPD and their association with the intensity of depressive and anxiety symptoms as well as medical determinants were identified. MATERIALS AND METHODS: In this cross-sectional study, 28 male patients with COPD risk class D were enrolled. The patients performed spirometry tests, Borg scale, 6-minute walking test, Hospital Anxiety and Depression Scale, and COPE Inventory were recorded. RESULTS: According to their higher coping subscale score, the depression score was the highest in patients with avoidance type coping and the lowest in patients with problem-focused coping (11.0 vs 5.6; P=0.042), respectively, patients with social support-focused coping having the highest anxiety score in contrast to patients with emotion-focused coping, which had the lowest anxiety score (11.6 vs 5.0; P=0.006). Regarding respiratory parameters, significant differences were present for the variation of the medians between the four groups only for forced vital capacity (FVC%) (the lowest FVC% was in patients with predominant social support-focused coping and the highest in patients with problem-focused coping) and 6-minute walking test (%) (the lowest score for patients with social support-focused coping and the highest value in patients with avoidance-type coping). Problem-coping score was significantly and positively associated with FVC% (Spearman's r=0.400; P=0.035), emotion-focused coping score was significantly and positively associated with FVC% (Spearman's r=0.395; P=0.038), and social support-focused coping score was negatively and significantly correlated with forced expiratory volume in 1 second/FVC% ratio (Spearman's r=0.389; P=0.041). A significant, negative correlation was found only between depression score and forced expiratory volume in 1 second (Spearman's r= 0.435; P=0.026) with respect to psychiatric symptoms. CONCLUSION: Coping styles in patients with COPD affect the intensity of associated depressive and anxiety symptoms as well as medical determinants, thus the coping style should be considered an important part in the multidisciplinary approach of these patients. PMID- 27382271 TI - Immediate effect of manual therapy on respiratory functions and inspiratory muscle strength in patients with COPD. AB - OBJECTIVE: The objective of this study was to investigate the immediate effect of manual therapy (MT) on respiratory functions and inspiratory muscle strength in patients with COPD. PARTICIPANTS AND METHODS: Thirty patients with severe COPD (eight females and 22 males; mean age 62.4+/-6.8 years) referred to pulmonary physiotherapy were included in this study. The patients participated in a single session of MT to measure the short-term effects. The lung function was measured using a portable spirometer. An electronic pressure transducer was used to measure respiratory muscle strength. Heart rate, breathing frequency, and oxygen saturation were measured with a pulse oximeter. For fatigue and dyspnea perception, the modified Borg rating of perceived exertion scale was used. All measurements were taken before and immediately after the first MT session. The ease-of-breathing visual analog scale was used for rating patients' symptoms subjectively during the MT session. RESULTS: There was a significant improvement in the forced expiratory volume in the first second, forced vital capacity, and vital capacity values (P<0.05). The maximal inspiratory pressure and maximal expiratory pressure values increased significantly after MT, compared to the pre MT session (P<0.05). There was a significant decrease in heart rate, respiratory rate (P<0.05), and dyspnea and fatigue perception (P<0.05). CONCLUSION: A single MT session immediately improved pulmonary function, inspiratory muscle strength, and oxygen saturation and reduced dyspnea, fatigue, and heart and respiratory rates in patients with severe COPD. MT should be added to pulmonary rehabilitation treatment as a new alternative that is fast acting and motivating in patients with COPD. PMID- 27382272 TI - Vitamin D should be supplemented more actively in elderly patients with coronary heart disease combined with COPD. AB - OBJECTIVE: It is not clear whether vitamin D should be actively supplemented in elderly patients suffering from an acute attack of COPD (AECOPD) and coronary heart disease (CHD). PATIENTS AND METHODS: The patients were divided into three groups according to specific criteria: patients with AECOPD (group A), patients with COPD combined with CHD (group B), and patients with CHD (group C). We measured the levels of vitamin D and analyzed the correlation between vitamin D and important electrolytes, including prealbumin, creatinine, hemoglobin, cystatin C, blood fat, blood calcium, and blood magnesium, and the nutrition state of the whole body. The serum B-type natriuretic peptide (BNP) was measured using an ELISA kit. RESULTS: The vitamin D level in group B was the lowest, followed by group A. When compared with group C, they all had statistical significance (P<0.05), but there was no statistical difference between groups A and B. There was no difference among the three groups when prealbumin, creatinine, hemoglobin, cystatin C, blood fat, blood calcium, and blood magnesium were compared. The level of BNP in the three groups increased, but it had no obvious correlation with the level of vitamin D (P>0.05). CONCLUSION: When elderly patients have coronary artery disease with AECOPD, vitamin D levels were obviously lower and were negatively correlated with the BNP. Low vitamin D levels, as well as poor nutrition, affect cardiopulmonary function and quality of living of elderly patients, especially female patients. Therefore, vitamin D should be supplemented more actively in the female patients suffering from AECOPD and CHD. PMID- 27382273 TI - Association between TNF-alpha -308 G/A polymorphism and COPD susceptibility: a meta-analysis update. AB - BACKGROUND AND OBJECTIVE: The association between TNF-alpha -308 G/A polymorphism and COPD remains controversial due to insufficiently strict study designs and small group sizes among different studies. In the present study, a meta-analysis update which followed a stricter procedure was performed to obtain a clearer understanding of this association. METHODS: A comprehensive database search was conducted to identify the case-control studies published up to July 2015 which reported an association between the TNF-alpha -308 G/A polymorphism and COPD risk. Data were extracted to calculate pooled odds ratios with 95% confidence intervals under the most appropriate genetic and allelic models. Sensitivity was analyzed, and heterogeneity as well as publication bias was assessed. RESULTS: Thirty-eight eligible studies, comprising 3,951 COPD cases and 5,110 controls, were included in this study, among which 22 studies comprising 2,067 COPD cases and 2,167 controls were performed in Asians, and 16 studies comprising 1,884 COPD cases and 2,943 controls were in non-Asians. The overall result showed that TNF alpha -308 G/A polymorphisms were significantly associated with increased COPD risk in both the codominant genetic and allelic models. Individuals with the GA or AA genotype were more susceptible to COPD development than those with the GG genotype. In addition, individuals with the AA genotype were more susceptible to developing COPD than those with the GA genotype. The subgroup analysis stratified by ethnicity supported the results in Asians but not in non-Asians. However, no association was found between TNF-alpha -308 G/A polymorphisms and COPD susceptibility either in Asians or in non-Asians in the meta-analysis conducted with restriction to former/current smokers. CONCLUSION: The present meta-analysis suggested that the TNF-alpha -308 G/A polymorphism was associated with an increased risk of COPD among Asians but not in non-Asians. Furthermore, individuals with the AA genotype of TNF-alpha -308 were more susceptible to developing COPD. PMID- 27382274 TI - Point-of-care procalcitonin test to reduce antibiotic exposure in patients hospitalized with acute exacerbation of COPD. AB - BACKGROUND: This study was conducted to investigate whether point-of-care (POC) procalcitonin (PCT) measurement can reduce redundant antibiotic treatment in patients hospitalized with acute exacerbation of COPD (AECOPD). METHODS: One hundred and twenty adult patients admitted with AECOPD were enrolled in this open label randomized trial. Patients were allocated to either the POC PCT-guided intervention arm (n=62) or the control arm, in which antibiotic therapy followed local guidelines (n=58). RESULTS: The median duration of antibiotic exposure was 3.5 (interquartile range [IQR] 0-10) days in the PCT-arm vs 8.5 (IQR 1-11) days in the control arm (P=0.0169, Wilcoxon) for the intention-to-treat population. The proportion of patients using antibiotics for >=5 days within the 28-day follow-up was 41.9% (PCT-arm) vs 67.2% (P=0.006, Fisher's exact) in the intention to-treat population. For the per-protocol population, the proportions were 21.1% (PCT-arm) vs 73.9% (P<0.00001, Fisher's exact). Within 28-day follow-up, one patient died in the PCT-arm and two died in the control arm. A composite harm end point consisting of death, rehospitalization, or intensive care unit admission, all within 28 days, showed no apparent difference. CONCLUSION: Our study shows that the implementation of a POC PCT-guided algorithm can be used to substantially reduce antibiotic exposure in patients hospitalized with AECOPD, with no apparent harm. PMID- 27382276 TI - Effect of outpatient therapy with inhaled corticosteroids on decreasing in hospital mortality from pneumonia in patients with COPD. AB - BACKGROUND AND OBJECTIVES: Inhaled corticosteroids (ICS) and long-acting inhaled bronchodilators (IBD) are beneficial for the management of COPD. Although ICS has been reported to increase the risk of pneumonia in patients with COPD, it remains controversial whether it influences mortality. Using a Japanese national database, we examined the association between preadmission ICS therapy and in hospital mortality from pneumonia in patients with COPD. METHODS: We retrospectively collected data from 1,165 hospitals in Japan on patients with COPD who received outpatient inhalation therapy and were admitted with pneumonia. Patients were categorized into those who received ICS with IBD and those who received IBD alone. We performed multivariate logistic regression analysis to examine the association between outpatient ICS therapy and in-hospital mortality, adjusting for the patients' backgrounds. RESULTS: Of the 7,033 eligible patients, the IBD alone group (n=3,331) was more likely to be older, have lower body mass index, poorer general conditions, and more severe pneumonia than the ICS with IBD group (n=3,702). In-hospital mortality was 13.2% and 8.1% in the IBD alone and the ICS with IBD groups, respectively. After adjustment for patients' backgrounds, the ICS with IBD group had significantly lower mortality than the IBD alone group (adjusted odds ratio, 0.80; 95% confidence interval, 0.68-0.94). Higher mortality was associated with older age, being male, lower body mass index, poorer general status, and more severe pneumonia. CONCLUSION: Outpatient inhaled ICS and IBD therapy was significantly associated with lower mortality from pneumonia in patients with COPD than treatment with IBD alone. PMID- 27382275 TI - Lung inflammation caused by inhaled toxicants: a review. AB - Exposure of the lungs to airborne toxicants from different sources in the environment may lead to acute and chronic pulmonary or even systemic inflammation. Cigarette smoke is the leading cause of chronic obstructive pulmonary disease, although wood smoke in urban areas of underdeveloped countries is now recognized as a leading cause of respiratory disease. Mycotoxins from fungal spores pose an occupational risk for respiratory illness and also present a health hazard to those living in damp buildings. Microscopic airborne particulates of asbestos and silica (from building materials) and those of heavy metals (from paint) are additional sources of indoor air pollution that contributes to respiratory illness and is known to cause respiratory illness in experimental animals. Ricin in aerosolized form is a potential bioweapon that is extremely toxic yet relatively easy to produce. Although the aforementioned agents belong to different classes of toxic chemicals, their pathogenicity is similar. They induce the recruitment and activation of macrophages, activation of mitogen-activated protein kinases, inhibition of protein synthesis, and production of interleukin-1 beta. Targeting either macrophages (using nanoparticles) or the production of interleukin-1 beta (using inhibitors against protein kinases, NOD-like receptor protein-3, or P2X7) may potentially be employed to treat these types of lung inflammation without affecting the natural immune response to bacterial infections. PMID- 27382277 TI - Reinjury risk of nano-calcium oxalate monohydrate and calcium oxalate dihydrate crystals on injured renal epithelial cells: aggravation of crystal adhesion and aggregation. AB - BACKGROUND: Renal epithelial cell injury facilitates crystal adhesion to cell surface and serves as a key step in renal stone formation. However, the effects of cell injury on the adhesion of nano-calcium oxalate crystals and the nano crystal-induced reinjury risk of injured cells remain unclear. METHODS: African green monkey renal epithelial (Vero) cells were injured with H2O2 to establish a cell injury model. Cell viability, superoxide dismutase (SOD) activity, malonaldehyde (MDA) content, propidium iodide staining, hematoxylin-eosin staining, reactive oxygen species production, and mitochondrial membrane potential (Deltapsim) were determined to examine cell injury during adhesion. Changes in the surface structure of H2O2-injured cells were assessed through atomic force microscopy. The altered expression of hyaluronan during adhesion was examined through laser scanning confocal microscopy. The adhesion of nano-calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) crystals to Vero cells was observed through scanning electron microscopy. Nano-COM and COD binding was quantitatively determined through inductively coupled plasma emission spectrometry. RESULTS: The expression of hyaluronan on the cell surface was increased during wound healing because of Vero cell injury. The structure and function of the cell membrane were also altered by cell injury; thus, nano crystal adhesion occurred. The ability of nano-COM to adhere to the injured Vero cells was higher than that of nano-COD crystals. The cell viability, SOD activity, and Deltapsim decreased when nano-crystals attached to the cell surface. By contrast, the MDA content, reactive oxygen species production, and cell death rate increased. CONCLUSION: Cell injury contributes to crystal adhesion to Vero cell surface. The attached nano-COM and COD crystals can aggravate Vero cell injury. As a consequence, crystal adhesion and aggregation are enhanced. These findings provide further insights into kidney stone formation. PMID- 27382278 TI - Controlled release of curcumin from curcumin-loaded nanomicelles to prevent peritendinous adhesion during Achilles tendon healing in rats. AB - We introduced curcumin-loaded nanomicelles into a tendon-healing model to evaluate their effects on tendon healing and adhesion. Three groups consisting of 36 rats underwent rupture and repair of the Achilles tendon. The treatment group received an injection of curcumin-loaded nanomicelles (gold nanorods [GNRs] 1/curcumin in polymeric nanomicelles [curc@PMs] at a dosage of 0.44 mg curcumin/kg in 0.1 mL saline) into the surgical site and exposed to laser postoperatively at weeks 1, 2, and 3, for three times 10 seconds each, on the surgical site in the rats that underwent tendon rupture and repair, while the other two groups received 0.44 mg curcumin/kg in 0.1 mL saline and 0.1 mL of saline, respectively. The specimens were harvested at 4 weeks and subjected to biomechanical and histological evaluation. The scoring results of tendon adhesion indicated that GNRs-1/curc@PMs group was in the lowest grade of peritendinous adhesions compared to the other groups. Histological assessment further confirmed the preventive effect of GNRs-1/curc@PMs on tendon adhesion. These findings indicated greater tendon strength with less adhesion in the group treated with GNRs-1/curc@PMs combined with laser exposure, and that nanoparticle-based therapy may be applied to prevent adhesion in clinical patients. PMID- 27382279 TI - Development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation. AB - Most of the dental surgeries require preoperative anesthetic and postoperative analgesic for painless procedures. A multidrug transmucosal drug delivery system loaded with lignocaine (Lig) base for immediate release and solid lipid nanoparticles (SLNs) of diclofenac (Dic) diethylamine for prolonged release was developed. SLNs were prepared by solvent emulsion-evaporation method with Precirol ATO 5 and Geleol as lipids and Pluronic F 68 as surfactant and optimized with Box-Behnken design for particle size and entrapment efficiency. SLNs were incorporated into the transmucosal patch (TP) prepared with hydroxypropyl cellulose-LF (HPC-LF) and with a backing layer of ethyl cellulose. Optimized SLNs and TP were characterized for Fourier transform infrared spectrophotometry, differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, in vitro release, ex vivo permeation through porcine buccal mucosa, Caco-2 permeability, and residual solvent analysis by gas chromatography. The TP was also evaluated for swelling index, in vitro residence time, tensile strength, and mucoadhesive strength. Preclinical pharmacokinetic, pharmacodynamic, and histopathological studies by application of TP on the gingiva of New Zealand rabbits were carried out. Particle size and entrapment efficiency of the optimized SLN "S8" were determined as 98.23 nm and 84.36%, respectively. The gingival crevicular fluid and tissue concentrations were greater than plasma concentrations with increase in C max and area under the curve (AUC) of Lig and Dic when compared to the control group. Pain perception by needle prick showed prolonged combined anesthetic and analgesic effect. The developed TP loaded with Lig base and Dic diethylamine-SLNs exhibited immediate and complete permeation with tissue accumulation of Lig followed by controlled prolonged release and tissue accumulation of Dic at the site of application. Thus, it could be anticipated from the in vivo studies that the developed TP provides immediate initial anesthetic effect, and the analgesic effect would be prolonged for 24 hours, since optimal gingival crevicular fluid and tissue levels of analgesic would be achieved, while the tissue remains anesthetized. PMID- 27382280 TI - Cyclosporine Amicellar delivery system for dry eyes. AB - BACKGROUND: The objectives of this study were to develop stable cyclosporine A (CsA) ophthalmic micelle solutions for dry-eye syndrome and evaluate their physicochemical properties and therapeutic efficacy. MATERIALS AND METHODS: CsA micelle solutions (MS-CsA) were created by a simple method with Cremophor EL, ethanol, and phosphate buffer. We investigated the particle size, pH, and osmolarity. In addition, long-term physical and chemical stability for MS-CsA was observed. To confirm the therapeutic efficacy, tear production in dry eye-induced rabbits was evaluated using the Schirmer tear test (STT). When compared to a commercial product, Restasis, MS-CsA demonstrated improvement in goblet-cell density and conjunctival epithelial morphology, as demonstrated in histological hematoxylin and eosin staining. RESULTS: MS-CsA had a smaller particle size (average diameter 14-18 nm) and a narrow size distribution. Physicochemical parameters, such as particle size, pH, osmolarity, and remaining CsA concentration were all within the expected range of 60 days. STT scores significantly improved in MS-CsA treated groups (P<0.05) in comparison to those of the Restasis-treated group. The number of goblet cells for rabbit conjunctivas after the administration of MS-CsA was 94.83+/-8.38, a significantly higher result than the 65.17+/-11.51 seen with Restasis. The conjunctival epithelial morphology of dry eye-induced rabbits thinned with loss of goblet cells. However, after 5 days of treatment with drug formulations, rabbit conjunctivas recovered epithelia and showed a relative increase in the number of goblet cells. CONCLUSION: The results of this study indicate the potential use of a novel MS for the ophthalmic delivery of CsA in treating dry eyes. PMID- 27382283 TI - Chemically cross-linked silk fibroin hydrogel with enhanced elastic properties, biodegradability, and biocompatibility. AB - In this study, the synthesis of silk fibroin (SF) hydrogel via chemical cross linking reactions of SF due to gamma-ray (gamma-ray) irradiation was investigated, as were the resultant hydrogel's properties. Two different hydrogels were investigated: physically cross-linked SF hydrogel and chemically cross-linked SF hydrogel irradiated at different doses of gamma-rays. The effects of the irradiation dose and SF concentration on the hydrogelation of SF were examined. The chemically cross-linked SF hydrogel was compared with the physically cross-linked one with regard to secondary structure and gel strength. Furthermore, the swelling behavior, crystallinity, and biodegradation of the SF hydrogels were characterized. To assay cell proliferation, the cell viability of human mesenchymal stem cells on the lyophilized SF hydrogel scaffolds was evaluated, and no significant cytotoxicity against human mesenchymal stem cells was observed. PMID- 27382282 TI - Robust aptamer-polydopamine-functionalized M-PLGA-TPGS nanoparticles for targeted delivery of docetaxel and enhanced cervical cancer therapy. AB - One limitation of current biodegradable polymeric nanoparticles (NPs) is the contradiction between functional modification and maintaining formerly excellent bioproperties with simple procedures. Here, we reported a robust aptamer polydopamine-functionalized mannitol-functionalized poly(lactide-co-glycolide) (M PLGA)-D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoformulation (Apt-pD-NPs) for the delivery of docetaxel (DTX) with enhanced cervical cancer therapy effects. The novel DTX-loaded Apt-pD-NPs possess satisfactory advantages: 1) increased drug loading content and encapsulation efficiency induced by star-shaped copolymer M-PLGA-TPGS; 2) significant active targeting effect caused by conjugated AS1411 aptamers; and 3) excellent long-term compatibility by incorporation of TPGS. Therefore, with simple preparation procedures and excellent bioproperties, the new functionalized Apt-pD-NPs could maximally increase the local effective drug concentration on tumor sites, achieving enhanced treatment effectiveness and minimizing side effects. In a word, the robust DTX-loaded Apt-pD-NPs could be used as potential nanotherapeutics for cervical cancer treatment, and the aptamer-polydopamine modification strategy could be a promising method for active targeting of cancer therapy with simple procedures. PMID- 27382281 TI - A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements. AB - Nanomaterials (NMs) are attractive for biomedical and pharmaceutical applications because of their unique physicochemical and biological properties. A major application area of NMs is drug delivery. Many nanomedicinal products (NMPs) currently on the market or in clinical trials are most often based on liposomal products or polymer conjugates. NMPs can be designed to target specific tissues, eg, tumors. In virtually all cases, NMPs will eventually reach the immune system. It has been shown that most NMs end up in organs of the mononuclear phagocytic system, notably liver and spleen. Adverse immune effects, including allergy, hypersensitivity, and immunosuppression, have been reported after NMP administration. Interactions of NMPs with the immune system may therefore constitute important side effects. Currently, no regulatory documents are specifically dedicated to evaluate the immunotoxicity of NMs or NMPs. Their immunotoxicity assessment is performed based on existing guidelines for conventional substances or medicinal products. Due to the unique properties of NMPs when compared with conventional medicinal products, it is uncertain whether the currently prescribed set of tests provides sufficient information for an adequate evaluation of potential immunotoxicity of NMPs. The aim of this study was therefore, to compare the current regulatory immunotoxicity testing requirements with the accumulating knowledge on immunotoxic effects of NMPs in order to identify potential gaps in the safety assessment. This comparison showed that immunotoxic effects, such as complement activation-related pseudoallergy, myelosuppression, inflammasome activation, and hypersensitivity, are not readily detected by using current testing guidelines. Immunotoxicity of NMPs would be more accurately evaluated by an expanded testing strategy that is equipped to stratify applicable testing for the various types of NMPs. PMID- 27382284 TI - A stabilizer-free and organic solvent-free method to prepare 10 hydroxycamptothecin nanocrystals: in vitro and in vivo evaluation. AB - 10-Hydroxycamptothecin (10-HCPT) is a promising anticancer drug with a wide spectrum of antitumor activities. Due to its poor solubility, the carboxylate form that shows high water solubility but minimal anticancer activity and pharmacokinetic defects is used in the marketed 10-HCPT injections, resulting in its limited clinical application. To develop a simple, safe, and highly effective drug delivery system, a modified acid-base microprecipitation combined with a high-pressure homogenization technique was adopted to prepare 10-HCPT nanocrystals. Neither organic solvents nor stabilizers were employed throughout the preparation process. The in vitro and in vivo performances of the resulting10 HCPT nanocrystals were investigated systematically. The nanocrystals were spherical with a small size of ~130 nm, and the actual drug-loading content was as high as 75%. The nanocrystals displayed a sustained release pattern and were proven to have a higher cell uptake and antiproliferative activity than the 10 HCPT injections. The 10-HCPT nanocrystals also showed enhanced drug accumulation in tumors and better anticancer efficacy in 4T1-bearing mice. In summary, the 10 HCPT nanocrystals prepared in this study seem to be a promising delivery system for a new form of 10-HCPT dosages. PMID- 27382286 TI - Deep brain stimulation of pallidal versus subthalamic for patients with Parkinson's disease: a meta-analysis of controlled clinical trials. AB - BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disorder that affects many people every year. Deep brain stimulation (DBS) is an effective nonpharmacological method to treat PD motor symptoms. This meta-analysis was conducted to evaluate the efficacy of subthalamic nucleus (STN)-DBS versus globus pallidus internus (GPi)-DBS in treating advanced PD. METHODS: Controlled clinical trials that compared STN-DBS to GPi-DBS for short-term treatment of PD in adults were researched up to November 2015. The primary outcomes were the Unified Parkinson's Disease Rating Scale Section (UPDRS) III score and the levodopa equivalent dosage (LED) after DBS. The secondary outcomes were the UPDRS II score and the Beck Depression Inventory (BDI) score. RESULTS: Totally, 13 studies containing 1,148 PD patients were included in this meta-analysis to compare STN DBS versus GPi-DBS. During the off-medication state, the pooled weighted mean difference (WMD) of UPDRS III and II scores were -2.18 (95% CI =-5.11 to 0.74) and -1.96 (95% CI =-3.84 to -0.08), respectively. During the on-medication state, the pooled WMD of UPDRS III and II scores were 0.15 (95% CI =-1.14 to 1.44) and 1.01 (95% CI =0.12 to 1.89), respectively. After DBS, the pooled WMD of LED and BDI were -254.48 (95% CI =-341.66) and 2.29 (95% CI =0.83 to 3.75), respectively. CONCLUSION: These results indicate that during the off-medication state, the STN DBS might be superior to GPi-DBS in improving the motor function and activities of daily living for PD patients; but during the on-medication state, the opposite result is observed. Meanwhile, the STN-DBS is superior at reducing the LED, whereas the GPi-DBS shows a significantly greater reduction in BDI score after DBS. PMID- 27382285 TI - The causes of new-onset epilepsy and seizures in the elderly. AB - With increasing age, the prevalence and incidence of epilepsy and seizures increases correspondingly. New-onset epilepsy in elderly people often has underlying etiology, including cerebrovascular diseases, primary neuron degenerative disorders, intracerebral tumors, and traumatic head injury. In addition, an acute symptomatic seizure cannot be called epilepsy, which manifests usually as a common symptom secondary to metabolic or toxicity factors in older people. In this review, we have mainly focused on the causes of new-onset epilepsy and seizures in elderly people. This knowledge will certainly help us to understand the reasons for high incidences of epilepsy and seizures in elderly people. We look forward to controlling epileptic seizures via the treatment of primary diseases in the future. PMID- 27382287 TI - Altered lower leg muscle activation patterns in patients with cerebral palsy during cycling on an ergometer. AB - OBJECTIVE: Cycling on a recumbent ergometer constitutes one of the most popular rehabilitation exercises in cerebral palsy (CP). However, no control is performed on how muscles are being used during training. Given that patients with CP present altered muscular activity patterns during cycling or walking, it is possible that an incorrect pattern of muscle activation is being promoted during rehabilitation cycling. This study investigated patterns of muscular activation during cycling on a recumbent ergometer in patients with CP and whether those patterns are determined by the degree of spasticity and of mobility. METHODS: Electromyographic (EMG) recordings of lower leg muscle activation during cycling on a recumbent ergometer were performed in 14 adult patients diagnosed with CP and five adult healthy participants. EMG recordings were done with an eight channel EMG system built in the laboratory. The activity of the following muscles was recorded: Musculus rectus femoris, Musculus biceps femoris, Musculus tibialis anterior, and Musculus gastrocnemius. The degree of muscle spasticity and mobility was assessed using the Modified Ashworth Scale and the Gross Motor Function Classification System, respectively. Muscle activation patterns were described in terms of onset and duration of activation as well as duration of cocontractions. RESULTS: Muscle activation in CP was characterized by earlier onsets, longer periods of activation, a higher occurrence of agonist-antagonist cocontractions, and a more variable cycling tempo in comparison to healthy participants. The degree of altered muscle activation pattern correlated significantly with the degree of spasticity. CONCLUSION: This study confirmed the occurrence of altered lower leg muscle activation patterns in patients with CP during cycling on a recumbent ergometer. There is a need to develop feedback systems that can inform patients and therapists of an incorrect muscle activation during cycling and support the training of a more physiological activation pattern. PMID- 27382289 TI - Characterizing sexual function in patients with generalized anxiety disorder: a pooled analysis of three vilazodone studies. AB - BACKGROUND: Vilazodone has been shown to reduce core symptoms of generalized anxiety disorder (GAD) in three randomized, double-blind, placebo-controlled trials. Since sexual dysfunction (SD) is not well characterized in GAD, a post hoc analysis of these trials was conducted to evaluate the effects of vilazodone on sexual functioning in GAD patients. MATERIALS AND METHODS: Data were pooled from one fixed-dose trial of vilazodone 20 and 40 mg/day (NCT01629966) and two flexible-dose studies of vilazodone 20-40 mg/day (NCT01766401, NCT01844115) in adults with GAD. Sexual functioning was assessed using the Changes in Sexual Functioning Questionnaire (CSFQ). Outcomes included mean change from baseline to end of treatment (EOT) in CSFQ total score and percentage of patients shifting from SD at baseline (CSFQ total score <=47 for males, <=41 for females) to normal functioning at EOT. Treatment-emergent adverse events related to sexual functioning were also analyzed. RESULTS: A total of 1,373 patients were included in the analyses. SD at baseline was more common in females (placebo, 46.4%; vilazodone, 49%) than in males (placebo, 35.1%; vilazodone, 40.9%). CSFQ total score improvement was found in both females (placebo, +1.2; vilazodone, +1.6) and males (placebo, +2.1; vilazodone, +1.0), with no statistically significant differences between treatment groups. The percentage of patients who shifted from SD at baseline to normal sexual functioning at EOT was higher in males (placebo, 40.6%; vilazodone, 35.7%) than in females (placebo, 24.9%; vilazodone, 34.9%); no statistical testing was performed. Except for erectile dysfunction and delayed ejaculation in vilazodone-treated males (2.4% and 2.1%, respectively), no treatment-emergent adverse events related to sexual functioning occurred in >=2% of patients in either treatment group. CONCLUSION: Approximately 35%-50% of patients in the vilazodone GAD studies had SD at baseline. Vilazodone and placebo had similar effects on CSFQ outcomes in both females and males, indicating a limited adverse impact on sexual functioning with vilazodone. PMID- 27382288 TI - Psychometric properties of the Spanish version of the Clinical Outcomes in Routine Evaluation - Outcome Measure. AB - OBJECTIVE: The objective of this paper is to assess the reliability and validity of the Spanish translation of the Clinical Outcomes in Routine Evaluation - Outcome Measure, a 34-item self-report questionnaire that measures the client's status in the domains of Subjective well-being, Problems/Symptoms, Life functioning, and Risk. METHOD: Six hundred and forty-four adult participants were included in two samples: the clinical sample (n=192) from different mental health and primary care centers; and the nonclinical sample (n=452), which included a student and a community sample. RESULTS: The questionnaire showed good acceptability and internal consistency, appropriate test-retest reliability, and acceptable convergent validity. Strong differentiation between clinical and nonclinical samples was found. As expected, the Risk domain had different characteristics than other domains, but all findings were comparable with the UK referential data. Cutoff scores were calculated for clinical significant change assessment. CONCLUSION: The Spanish version of the Clinical Outcomes in Routine Evaluation - Outcome Measure showed acceptable psychometric properties, providing support for using the questionnaire for monitoring the progress of Spanish speaking psychotherapy clients. PMID- 27382290 TI - Comparison of treatment outcomes in severe personality disorder patients with or without substance use disorders: a 36-month prospective pragmatic follow-up study. AB - BACKGROUND: Concurrent personality disorder (PD) and substance use disorder (SUD) are common in clinical practice. However, SUD is the main criterion for study exclusion in most psychotherapeutic studies of PD. As a result, data on treatment outcomes in patients with concurrent PD/SUD are scarce. METHODS: The study sample consisted of 51 patients diagnosed with severe PD and admitted for psychotherapeutic treatment as a part of routine mental health care. All patients were diagnosed with PD according to the Structured Clinical Interview for PD. Patients were further assessed (DSM-IV diagnostic criteria) to check for the presence of concurrent SUD, with 28 patients diagnosed with both disorders (PD SUD). These 28 cases were then compared to the 23 patients without SUD (PD-nSUD) in terms of psychiatric hospitalizations and psychiatric emergency room (ER) visits before and during the 6-month therapeutic intervention and every 6 months thereafter for a total of 36 months. RESULTS: The baseline clinical characteristics correspond to a sample of PD patients (78% met DSM-IV criteria for borderline PD) with poor general functioning and a high prevalence of suicide attempts and self-harm behaviors. Altogether, the five outcome variables - the proportion and the number of psychiatric inpatient admissions, the number of days hospitalized, and the proportion and the number of psychiatric ER visits - improved significantly during the treatment period, and this improvement was maintained throughout the follow-up period. Although PD-SUD patients had more psychiatric hospitalizations and ER visits than PD-nSUD patients during follow up, the differences between these two groups remained stable over the study period indicating that the treatment was equally effective in both groups. CONCLUSION: Specialized psychotherapy for severe PD can be effectively applied in patients with concurrent PD-SUD under usual practice conditions. These findings suggest that exclusion of patients with dual disorders from specialized treatments is unjustified. PMID- 27382291 TI - Effects of perpetrator identity on suicidality and nonsuicidal self-injury in sexually victimized female adolescents. AB - PURPOSE: Child sexual abuse and sexual dating violence victimization are common problems that are known to have long-term negative consequences. This study aimed to compare the sociodemographic, abuse-related, and clinical features of female adolescents who were sexually abused by different perpetrators, and identify the factors associated with suicidality and nonsuicidal self-injury (NSSI) in these cases. PATIENTS AND METHODS: Data of 254 sexually abused female adolescents between the ages of 12-18 years were evaluated. The cases were classified into three groups, namely "sexual dating violence", "incest", and "other child sexual abuse", according to the identity of the perpetrator. The three groups were compared in terms of sociodemographic, abuse-related, and clinical features. RESULTS: Major depressive disorder was the most common psychiatric diagnosis, which was present in 44.9% of the cases. Among all victims, 25.6% had attempted suicide, 52.0% had suicidal ideation, and 23.6% had NSSI during the postabuse period. A logistic regression analysis revealed that attempted suicide was predicted by dating violence victimization (adjusted odds ratio [AOR] =3.053; 95% confidence interval [CI] =1.473, 6.330) and depression (AOR =2.238; 95% CI =1.226, 4.086). Dating violence victimization was also the strongest predictor of subsequent suicidal ideation (AOR =3.500; 95% CI =1.817, 6.741). In addition, revictimization was determined to be an important risk factor for both suicidal ideation (AOR =2.897; 95% CI =1.276, 6.574) and NSSI (AOR =3.847; 95% CI =1.899, 7.794). CONCLUSION: Perpetrator identity and revictimization are associated with negative mental health outcomes in sexually victimized female adolescents. Increased risk of suicidality and NSSI should be borne in mind while assessing cases with dating violence and revictimization histories, in particular. PMID- 27382292 TI - A door-to-door survey to estimate the prevalence of Parkinsonism in Pakistan. AB - INTRODUCTION: Parkinson's disease (PD) occurs in all races and cultures, and population-related differences in frequency may provide etiological clues. The present study was designed to explore the prevalence of PD and Parkinsonism in Pakistan, the world's sixth most populous country, for which no published prevalence data are available. METHODS: We conducted a three-phase door-to-door survey in two districts of the Khyber Pakhtunkhwa province of Pakistan, to assess the prevalence of PD and Parkinsonism in a sample of 4,000 individuals aged 50 years and above. RESULTS: We identified 14 cases of Parkinsonism, eleven with a diagnosis of idiopathic PD. The overall prevalence estimates were 1.7/100 (95% confidence interval [CI]: 0.9-2.46) for Parkinsonism and 1.28/100 (95% CI: 0.6 1.94) for PD in persons aged 65 years and above. The age-standardized prevalence of PD (aged 65 years and above), normalized to the USA population in 2000, was 1.33/100, which is similar to that observed in other human populations. Of the total 14 cases, five were newly diagnosed and four had a family history of PD. CONCLUSION: The estimated prevalence rates in Pakistan are similar to those observed in other human populations. The frequency of familial Parkinsonism is also equivalent to previous estimates. PMID- 27382293 TI - Effect of adjuvant sleep hygiene psychoeducation and lorazepam on depression and sleep quality in patients with major depressive disorders: results from a randomized three-arm intervention. AB - BACKGROUND: Sleep disturbances are a common co-occurring disturbance in patients with major depressive disorders (MDDs) and accordingly deserve particular attention. Using a randomized design, we investigated the effects of three different adjuvant interventions on sleep and depression among patients with MDD: a sleep hygiene program (SHP), lorazepam (LOR), and their combination (SHP-LOR). METHODS: A total of 120 outpatients with diagnosed MDD (mean age: 48.25 years; 56.7% females) and treated with a standard SSRI (citalopram at 20-40 mg at therapeutic level) were randomly assigned to one of the following three conditions: SHP (n=40), LOR (1 mg/d; n=40), SHP-LOR (1 mg/d; n=40). At the beginning and at the end of the study 8 weeks later, patients completed two questionnaires, the Pittsburgh Sleep Quality Index to assess sleep and the Beck Depression Inventory to assess symptoms of depression. RESULTS: Sleep disturbances decreased over time and in all groups. No group differences or interactions were observed. Symptoms of depression decreased over time and in all three groups. Reduction in symptoms of depression was greatest in the SHP-LOR group and lowest in the LOR group. CONCLUSION: The pattern of results suggests that all three adjuvant treatments improved symptoms of sleep disturbances and depression, with greater benefits for the SHP-LOR for symptoms of depression, but not for sleep. Nevertheless, risks and benefits of benzodiazepine prescriptions should be taken into account. PMID- 27382294 TI - Monitoring intracranial pressure utilizing a novel pattern of brain multiparameters in the treatment of severe traumatic brain injury. AB - The aim of the study was to evaluate the clinical value of multiple brain parameters on monitoring intracranial pressure (ICP) procedures in the therapy of severe traumatic brain injury (sTBI) utilizing mild hypothermia treatment (MHT) alone or a combination strategy with other therapeutic techniques. A total of 62 patients with sTBI (Glasgow Coma Scale score <8) were treated using mild hypothermia alone or mild hypothermia combined with conventional ICP procedures such as dehydration using mannitol, hyperventilation, and decompressive craniectomy. The multiple brain parameters, which included ICP, cerebral perfusion pressure, transcranial Doppler, brain tissue partial pressure of oxygen, and jugular venous oxygen saturation, were detected and analyzed. All of these measures can control the ICP of sTBI patients to a certain extent, but multiparameters associated with brain environment and functions have to be critically monitored simultaneously because some procedures of reducing ICP can cause side effects for long-term recovery in sTBI patients. The result suggested that multimodality monitoring must be performed during the process of mild hypothermia combined with conventional ICP procedures in order to safely target different clinical methods to specific patients who may benefit from an individual therapy. PMID- 27382295 TI - Aggression in autism spectrum disorder: presentation and treatment options. AB - Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent difficulties in social communication and social interaction, coupled with restricted, repetitive patterns of behavior or interest. Research indicates that aggression rates may be higher in individuals with ASD compared to those with other developmental disabilities. Aggression is associated with negative outcomes for children with ASD and their caregivers, including decreased quality of life, increased stress levels, and reduced availability of educational and social support. Therapeutic strategies including functional behavioral assessment, reinforcement strategies, and functional communication training may have a significant impact in reducing the frequency and intensity of aggressive behavior in individuals with ASD. Pharmacologic treatments, particularly the use of second-generation antipsychotics, may also be of some benefit in reducing aggression in individuals with ASD. With the ever-increasing rate of ASD diagnosis, development of effective therapeutic and pharmacologic methods for preventing and treating aggression are essential to improving outcomes in this disorder. PMID- 27382296 TI - Noninvasive FFR derived from coronary CT angiography in the management of coronary artery disease: technology and clinical update. AB - After a decade of clinical use of coronary computed tomographic angiography (CCTA) to evaluate the anatomic severity of coronary artery disease, new methods of deriving functional information from CCTA have been developed. These methods utilize the anatomic information provided by CCTA in conjunction with computational fluid dynamics to calculate fractional flow reserve (FFR) values from CCTA image data sets. Computed tomography-derived FFR (CT-FFR) enables the identification of lesion-specific drop noninvasively. A three-dimensional CT-FFR modeling technique, which provides FFR values throughout the coronary tree (HeartFlow FFRCT analysis), has been validated against measured FFR and is now approved by the US Food and Drug Administration for clinical use. This technique requires off-site supercomputer analysis. More recently, a one-dimensional computational analysis technique (Siemens cFFR), which can be performed on on site workstations, has been developed and is currently under investigation. This article reviews CT-FFR technology and clinical evidence for its use in stable patients with suspected coronary artery disease. PMID- 27382297 TI - Association between perceived lifetime risk of cardiovascular disease and calculated risk in a male population in Brazil. AB - AIM: Cardiovascular disease is the major cause of morbidity and mortality across the world. Despite health campaigns to improve awareness of cardiovascular risk factors, there has been little improvement in cardiovascular mortality. In this study, we sought to examine the association between cardiovascular risk factors and people's perception on cardiovascular risk. METHODS: This was an epidemiological, cross-sectional, descriptive, prospective study of Masonic men aged >40 years in Boa Vista, Brazil. Participants completed a health survey, which included three questions about perception of their stress level, overall health status, and risk of a heart attack. In addition, demographic and biological data were collected. RESULTS: A total of 101 Masonic men took part in the study; their mean age (+/- standard deviation) was 55.35+/-9.17 years and mean body mass index was 28.77+/-4.51 kg/m(2). Answers to the lifestyle questionnaire suggested an overall healthy lifestyle, including good diet and moderate exercise, although despite this ~80% were classified as overweight or obese. The majority of participants felt that they had a low stress level (66.3%), good overall general health (63.4%), and were at low risk of having a heart attack (71.3%). Masons who were overweight were significantly more likely to perceive themselves to be at risk of a heart attack (P=0.025). CONCLUSION: Despite over half of participants having a moderate to high risk of cardiovascular disease according to traditional risk factors, less than a third perceived themselves to be at high risk. Public health campaigns need to better communicate the significance of traditional cardiovascular risk in order to improve awareness of risk among the general population. PMID- 27382298 TI - XuefuZhuyu Tang exerts antitumor effects by inhibiting glioma cell metastasis and invasion via regulating tumor microenvironment. AB - BACKGROUND: XuefuZhuyu Tang (XZT) is a traditional Chinese herb used for destagnation and is currently being used for oncotherapy. This study was intended to assess the effects of XZT on glioma along with its anticancer mechanism. MATERIALS AND METHODS: U251 cells were divided into five groups: CNC (cells were cultured with normal saline), TSC (cells were treated with TaohongSiwu Tang [TST]), XSC (cells were treated with XZT), THC (cells were treated with homogenate of TST), and XHC (cells were treated with homogenate of XZT). The mRNA and protein expression of VEGF/VEGFR, CXCR4/CXCL12, and TIMP1/MMP9/MMP2 were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. Moreover, MTT assay, transwell assay, wound-healing assay, and flow cytometry were conducted to assess the cell viability, cell migration and invasion, cell motility, and cell apoptosis of U251 cells, respectively. In vivo, three mice models (group CNM, gavaging saline; group TSM, gavaging TST; group XZM, gavaging XZT) were constructed after establishing xenograft mice models. Then, models were examined using hematoxylin and eosin staining, RT-PCR, and Western blotting. RESULTS: In vitro, XZT significantly upregulated TIMP1 expression and downregulated the expression of VEGF, VEGFR, CXCR4, CXCL12, MMP9, and MMP2 in U251 cells (all P<0.05). In addition, XZT inhibited cell proliferation, invasion, and migration and induced cell apoptosis. In vivo, the average expression level of VEGF, CXCL12, MMP9, and MMP2 was downregulated in the XZM group compared with the control and TSM groups (all P<0.05). Tumor volumes in the XZM group were significantly lower than those in the CNM and TSM groups (all P<0.05). CONCLUSION: XZT may suppress glioma growth and decrease expression levels of VEGF, CXCL12, MMP9, and MMP2. We speculate that XZT may be a potential therapeutic herb for curing glioma. PMID- 27382299 TI - Roles of microRNA-99 family in human glioma. AB - OBJECTIVE: Deregulation of microRNA (miR)-99 family members (miR-99a, miR-99b, and miR-100) has been reported to play a crucial role in many cancer types. However, their roles in human gliomas have not been fully elucidated. This study aimed to investigate the expression patterns of miR-99a, miR-99b, and miR-100 in glioma tissues and to evaluate their expression profiles with respect to tumor progression. METHODS: Quantitative real-time polymerase chain reaction was performed to detect the expression levels of miR-99a, miR-99b, and miR-100 in glioma and matched non-neoplastic brain tissues. Then, the associations of their expression with various clinicopathological features of glioma patients were statistically analyzed. Moreover, the roles of miR-99a, miR-99b, and miR-100 in regulating glioma cell migration and invasion were determined via transwell assay in vitro. RESULTS: Compared with non-neoplastic brain tissues, miR-99a, miR-99b, and miR-100 expression levels were all significantly decreased in glioma tissues (all P<0.001). miR-99a-low, miR-99b-low, and miR-100-low expression more frequently occurred in glioma patients with low Karnofsky performance score (<90) and high World Health Organization grade (III-IV). Further functional experiments revealed that the enforced expression of miR-99a, miR-99b, and miR-100 resulted in the inhibition of cellular migration and invasion in glioma cells. CONCLUSION: Our results strongly suggest that the aberrant expression of miR-99a, miR-99b, and miR-100 may be a common feature in human gliomas with aggressive clinicopathological features and may participate in malignant phenotypes of the tumors. These findings highlight the potential of the three miR-99 family members as novel therapeutic targets for human gliomas. PMID- 27382300 TI - A systematic review and meta-analysis of the risk of diarrhea associated with vandetanib treatment in carcinoma patients. AB - BACKGROUND AND PURPOSE: Vandetanib is a promising anticancer targeted agent for treating advanced carcinomas, such as non-small-cell lung cancer, small-cell lung cancer, breast cancer, malignant glioma, hepatocellular cancer, and unresectable, locally advanced, or metastatic medullary thyroid cancer. However, diarrhea is a frequently reported adverse event. The incidence of vandetanib-associated diarrhea varies extensively in different study populations and has not been carefully estimated. This systematic review and meta-analysis of clinical trials aims to figure out the overall risks of all-grade and high-grade diarrhea during vandetanib treatment and get a better understanding of its prediction and management. MATERIALS AND METHODS: A comprehensive search was performed in EMBASE, PubMed, and Cochrane Library for clinical trials studying vandetanib and diarrhea prior to April 2015. Eligible articles were selected according to the inclusion criteria. Data were extracted to calculate the summary incidence of all grade and high-grade diarrhea caused by vandetanib treatment. RESULTS: Thirteen clinical trials that involved 3,264 patients were included in this meta-analysis. The overall incidences of all-grade and high-grade diarrhea caused by vandetanib treatment were 52.1% (95% confidence interval [CI], 48.3%-55.8%) and 5.6% (95% CI, 4.4%-76.7%), respectively. The risk ratios of the all-grade and high-grade diarrhea for vandetanib arm versus control arm were 1.932 (95% CI, 1.746-2.138; P<0.001) and 3.190 (95% CI, 2.061-4.938; P<0.001), respectively. Studies with small-cell lung cancer demonstrated the highest incidence of all-grade diarrhea (78.85%) and high-grade diarrhea (17.31%), whereas the lowest incidences of all grade (42.11%) and high-grade (2.67%) diarrhea are seen in patients with hepatocellular carcinoma and non-small-cell lung cancer, respectively. CONCLUSION: Our findings demonstrate that the administration of vandetanib leads to a significantly increased risk of diarrhea, which varies in different carcinoma patients. Early recognition and timely management may be key factors to avoid dose reduction, drug interruption, and drug discontinuation, which is significant to maximize the treatment benefits. PMID- 27382301 TI - The effects of miR-1207-5p expression in peripheral blood on cisplatin-based chemosensitivity of primary gallbladder carcinoma. AB - OBJECTIVE: The aim of this study was to investigate the association between miR 1207-5p expression in peripheral blood and the chemosensitivity of primary gallbladder carcinoma (PGBC). METHODS: A total of 85 patients with PGBC undergoing preoperative chemotherapy were divided into effective (n=18) and ineffective (n=67) groups. Another 70 healthy individuals were selected as the control group. An miR-1207-5p mimic (mimic group), an inhibitor (inhibitor group), and a negative control (NC group) sequence were transfected into human gallbladder carcinoma GBC-SD cells. Real-time quantitative polymerase chain reaction was used to determine miR-1207-5p expression. After 48 hours of cisplatin treatment, CCK-8 method was used to detect cell proliferation and flow cytometry were performed to examine cell apoptosis. RESULTS: miR-1207-5p expression in peripheral blood was significantly associated with tumor node metastasis staging of PGBC (P<0.05). Before chemotherapy, miR-1207-5p expression in patients was higher than in healthy individuals (P<0.05). After chemotherapy, the effective group had lower miR-1207-5p expression than the ineffective group (P<0.05). The rates of positive expression of Ki67 protein in the effective group were significantly lower than those in the ineffective group (P<0.05). Receiver operating characteristic curves showed that the area under curve, sensitivity, and specificity of miR-1207-5p used to diagnose PGBC were 0.898, 77.6%, and 97.1% at a cutoff of 1.470, respectively. After 48 hours of cisplatin treatment, compared with the NC group and nontransfected (non-T) group, the mimic group had decreased rates of cell inhibition and apoptosis, but the inhibitor group had increased rates (all P<0.05). The expression levels of caspase3 protein were increased in the mimic group and decreased in the inhibitor group. Cell survival rates in the mimic group at different time points after cisplatin treatment were significantly higher than the corresponding rates in the NC and non-T groups, whereas the cell survival rates in the inhibitor group were significantly lower than the rates in the NC and non-T groups (all P<0.05). The concentration and action time of cisplatin were negatively associated with the cell survival rate in each group (all P<0.05). CONCLUSION: Cisplatin-based chemosensitivity of PGBC increased as expression of miR-1207-5p in peripheral blood declined. Thus, miR 1207-5p appears to be a promising and novel chemosensitizer for the treatment of PGBC. PMID- 27382302 TI - MicroRNA-190 regulates FOXP2 genes in human gastric cancer. AB - OBJECTIVE: To investigate how microRNA-190 (miR-190) regulates FOXP2 genes in gastric cancer (GC) cell line SGC7901. METHODS: We identified that miR-190 could target FOXP2 genes by using dual luciferase enzyme assay. Precursor fragment transfection of miR-190 was performed with GC cell line SGC7901 and human gastric mucosal cell line GES-1. miR-190 expression was detected by reverse transcription polymerase chain reaction (RT-PCR) and FOXP2 protein expression was measured by Western blotting. RESULTS: FOXP2-3'-untranslated region (UTR) in miR-190 transfection group was significantly decreased as compared with other groups. There were no significant differences in fluorescence signals of FOXP2mut-3'-UTR in each group. Therefore, it was assumed that miR-190 can target FOXP2 genes. Through RT-PCR verification, it was observed that the expression level of miR-190 was significantly higher in GC cell line SGC7901 than in human gastric mucosa cell line GES-1 after transfection with miR-190 mimics. The expression level of miR-190 was significantly higher in GES-1 cells than in SGC7901 cells after transfection with miR-190 inhibitors. Western blotting results showed the expression level of FOXP2 was significantly lower in GC cell line SGC7901 than in GES-1 cells. Compared with blank, mimics control, and inhibitors control groups, the miR-190 mimics group showed significantly enhanced proliferation, migration, and invasion abilities, while miR-190 inhibitors group showed decreased abilities toward proliferation, migration, and invasion (P<0.05). The transcription level of miR-190 and the expression level of FOXP2 in tumor tissues and adjacent normal tissues in GC patients were verified to be consistent with those of cell line experiments. CONCLUSION: Upregulation of miR-190 can lead to downregulation of FOXP2 protein expression. miR-190 may serve as a potential target for GC diagnosis. PMID- 27382303 TI - Potential role of S-adenosylmethionine in osteosarcoma development. AB - The metastatic form of osteosarcoma is a life threatening one since it metastasizes to the lungs. The major cause of metastatic osteosarcoma is hypomethylation of numerous genes that undergo overexpression to enable the progression of the disease. In the present study, S-adenosylmethionine (SAM), a predominant methyl donor, was administered to find out its effects on osteosarcoma progression. As evidence of tumor suppression, the SAM-treated mouse tissue was analyzed histologically, which exemplifies the control that SAM has over abnormal cell proliferation, especially on primary osteosarcoma, but it lacks positive effects on metastatic osteosarcoma. At the molecular level, the successful inhibition of primary osteosarcoma was found to be associated with a lower expression of Sox2, a protein highly expressed in osteosarcoma stem cells, along with an upregulated expression of TCTP. The data suggest that the administration of SAM has a positive role in treating primary osteosarcoma, but it has no role in suppressing metastatic osteosarcoma. The decreased expression of Sox2 together with upregulation of TCTP following SAM administration indicates that SAM has a control over primary osteosarcoma. PMID- 27382304 TI - Dose-enhanced combined priming regimens for refractory acute myeloid leukemia and middle-and-high-risk myelodysplastic syndrome: a single-center, retrospective cohort study. AB - OBJECTIVE: To assess chemotherapeutic regimens for refractory acute myeloid leukemia (AML) and middle-and-high-risk myelodysplastic syndrome (MDS). METHODS: Between 2004 and 2014, 44 patients with refractory AML and 36 patients with MDS were treated with new priming regimens (CHAG, CHTG, CHMG, or CTMG), and 77 patients with refractory AML and 52 patients with MDS were treated with conventional priming regimens (CHG or CAG). This was a single-center retrospective analysis of remission, adverse event, mortality, and survival. The capacity of clinical features (including the expression of co-stimulatory molecule B7.1 on tumor cells) to influence survival was assessed by multivariate Cox regression. RESULTS: Complete and partial remission rates (RRs) were significantly higher in AML patients treated with new regimens compared to conventional ones (68.2% vs 13.6%, P<0.05). Complete and partial remission were also significantly higher in patients with MDS treated with new regimens (55.6% vs 19.4%, P<0.05). However, although survival advantages were observed in the first year, the new regimens did not significantly improve 3-year overall survival (P>0.05). Patients administered the new regimens experienced more severe and sustained myelosuppression (P<0.05), but no severe adverse events or treatment-related deaths were observed. The rate of non-hematological side effects did not differ significantly between treatment regimens (P>0.05). Both RR and B7.1 expression were significantly higher in patients with AML-M2 and M5 (P<0.05). CONCLUSION: The new priming regimens improved the RR, lowered the recurrence rate, and improved survival in AML and middle-and-high-risk MDS, without significantly increasing adverse events. PMID- 27382305 TI - Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment. AB - OBJECTIVES: If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs). No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. METHODS: We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1), paclitaxel (200 mg/m(2), d1), and gemcitabine (1,000 mg/m(2) d1, 8) for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS) and overall survival (OS) were correlated to response, surgery, and clinical features. RESULTS: In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors-7th edition staging system). A total of 36 (62%) patients achieved partial response (PR), and six (10%) progressions were recorded. Grade 3-4 hematological toxicity was observed in 36 (62%) cases. After chemotherapy, 37 (64%) patients underwent surgery followed by adjuvant radiotherapy, and two patients received radical intent radiotherapy. The median PFS and OS were 11 months and 23 months, respectively. Both PFS and OS were significantly correlated to objective response (P<0.0001) and surgery (P<0.0001 and P=0.002). Patients obtaining PR and receiving local treatment achieved a median PFS and OS of 35 and 48 months, respectively. Median PFS and OS of patients not achieving PR or not receiving local treatment were 5-7 and 11-15 months, respectively. The extension of surgery did not affect the outcome. CONCLUSION: The multimodality treatment was feasible, and triple-agent induction was associated with a considerable rate of PR. Patients achieving PR and receiving radical surgery or radiotherapy (53%) achieved a median OS of 4 years. PMID- 27382306 TI - Can GSTM1 and GSTT1 polymorphisms predict clinical outcomes of chemotherapy in gastric and colorectal cancers? A result based on the previous reports. AB - BACKGROUND: Gastric and colorectal cancers remain the major causes of cancer related death. Although chemotherapy improves the prognosis of the patients with gastrointestinal cancers, some patients do not benefit from therapy and are exposed to the adverse effects. The polymorphisms in genes including GSTM1 and GSTT1 have been explored to predict therapeutic efficacy; however, the results were inconsistent and inconclusive. MATERIALS AND METHODS: A systematic review and meta-analysis was performed by searching relevant studies about the association between the GSTM1 and GSTT1 polymorphisms and chemotherapy efficacy in gastrointestinal cancers in databases such as PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure, and Wanfang database up to January 10, 2016. Subgroup analyses were also performed according to ethnicity, cancer type, evaluation criteria, study type, chemotherapy type, and age. RESULTS: A total of 19 articles containing 3,217 cases were finally included. Overall analysis suggested that no significance was found between overall toxicity, neurotoxicity, neutropenia, gastrointestinal toxicity, tumor response, and progression-free survival, and the polymorphisms in GSTM1 and GSTT1, while GSTM1 polymorphism associated with overall survival (OS; hazard ratio =1.213, 95% confidence interval =1.060-1.388, P=0.005). Subgroup analyses suggested that neurotoxicity was associated with GSTM1 polymorphism in the Asian population, neutropenia was associated with GSTM1 polymorphism in palliative chemotherapy and older patients (mean age >60 years), and tumor response was associated with GSTT1 polymorphism in gastric cancer and responders defined by complete and partial responses. Meanwhile, GSTM1 was associated with OS in Caucasians, Asians, those with colorectal cancer, and patients with mean age <60 years. GSTT1 polymorphism was also associated with OS in Caucasians and patients with mean age >60 years. CONCLUSION: The polymorphisms in GSTM1 and GSTT1 did not associate with the chemotherapy-related toxicity in gastrointestinal cancers, while GSTT1 polymorphism associated with OS, and further well-designed, larger-scale epidemiological studies are needed to validate our results. PMID- 27382308 TI - Correlation of primary middle and distal esophageal cancers motion with surrounding tissues using four-dimensional computed tomography. AB - PURPOSE: To investigate the correlation of gross tumor volume (GTV) motion with the structure of interest (SOI) motion and volume variation for middle and distal esophageal cancers using four-dimensional computed tomography (4DCT). PATIENTS AND METHODS: Thirty-three patients with middle or distal esophageal carcinoma underwent 4DCT simulation scan during free breathing. All image sets were registered with 0% phase, and the GTV, apex of diaphragm, lung, and heart were delineated on each phase of the 4DCT data. The position of GTV and SOI was identified in all 4DCT phases, and the volume of lung and heart was also achieved. The phase relationship between the GTV and SOI was estimated through Pearson's correlation test. RESULTS: The mean peak-to-peak displacement of all primary tumors in the lateral (LR), anteroposterior (AP), and superoinferior (SI) directions was 0.13 cm, 0.20 cm, and 0.30 cm, respectively. The SI peak-to-peak motion of the GTV was defined as the greatest magnitude of motion. The displacement of GTV correlated well with heart in three dimensions and significantly associated with bilateral lung in LR and SI directions. A significant correlation was found between the GTV and apex of the diaphragm in SI direction (r left=0.918 and r right=0.928). A significant inverse correlation was found between GTV motion and varying lung volume, but the correlation was not significant with heart (r LR=-0.530, r AP=-0.531, and r SI=-0.588) during respiratory cycle. CONCLUSION: For middle and distal esophageal cancers, GTV should expand asymmetric internal margins. The primary tumor motion has quite good correlation with diaphragm, heart, and lung. PMID- 27382307 TI - Risk of venous and arterial thromboembolic events associated with anti-VEGF agents in advanced non-small-cell lung cancer: a meta-analysis and systematic review. AB - AIMS: To assess the incidence and risk of arterial and venous thromboembolic events (ATEs and VTEs) associated with antivascular endothelial growth factor (VEGF) agents, including VEGF receptor-tyrosine kinase inhibitors and VEGF monoclonal antibodies, in advanced non-small-cell lung cancer (NSCLC) patients. METHODS: We performed a broad search of PubMed for relevant trials. Prospective randomized trials evaluating therapy with or without anti-VEGF agents in patients with advanced NSCLC were included for analysis. Data on VTEs and ATEs were extracted. The overall incidence, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were pooled according to the heterogeneity of included trials. RESULTS: A total of 13,436 patients from 23 trials were included for analysis. Our results showed that anti-VEGF agents significantly increased the risk of developing high-grade ATEs (Peto OR: 1.44, 95% CI: 1.00-2.07, P=0.048), but not for all-grade ATEs (Peto OR: 0.94, 95% CI: 0.56-1.59, P=0.82) compared with controls. Additionally, no increased risk of all-grade and high-grade VTEs (Peto OR: 0.94, 95% CI: 0.67-1.31, P=0.71 and Peto OR: 0.95, 95% CI: 0.73-1.22, P=0.67, respectively) was observed in advanced NSCLC patients receiving anti-VEGF agents. CONCLUSION: The use of anti-VEGF agents in advanced NSCLC patients significantly increased the risk of high-grade ATEs, but not for VTEs. Clinicians should be aware of the risk of severe ATEs with administration of these drugs in advanced NSCLC patients. PMID- 27382309 TI - Intrinsic resistance to EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer with activating EGFR mutations. AB - Identifying activating EGFR mutations is a useful predictive strategy that helps select a population of advanced non-small-cell lung cancer (NSCLC) patients for treatment with EGFR tyrosine kinase inhibitors (TKIs). Patients with sensitizing EGFR mutations (predominantly an in-frame deletion in exon 19 and an L858R substitution) are highly responsive to first-generation EGFR TKIs, such as gefitinib and erlotinib, and show improved progression-free survival without serious side effects. However, all patients with activating EGFR mutations who are initially responsive to EGFR TKIs eventually develop acquired resistance after a median progression-free survival of 10-16 months, followed by disease progression. Moreover, ~20%-30% of NSCLC patients have no objective tumor regression on initial EGFR TKI treatment, although they harbor an activating EGFR mutation. These patients represent an NSCLC subgroup that is defined as having intrinsic or primary resistance to EGFR TKIs. Different mechanisms of acquired EGFR TKI resistance have been identified, and several novel compounds have been developed to reverse acquired resistance, but little is known about EGFR TKI intrinsic resistance. In this review, we summarize the latest findings involving mechanisms of intrinsic resistance to EGFR TKIs in advanced NSCLC with activating EGFR mutations and present possible therapeutic strategies to overcome this resistance. PMID- 27382310 TI - Association of polymorphisms in interleukin-8 gene with cancer risk: a meta analysis of 22 case-control studies. AB - Interleukin-8 (IL-8) is a kind of chemokine that plays an important role in the development and progression of many human malignancies. Previous studies have uncovered that polymorphisms in IL-8 is associated with the risk of many cancer types, but the results were inconsistent and inconclusive. In the present study, we aimed to explore the roles of IL-8 polymorphisms (rs2227307, rs2227306, +678T/C, rs1126647, and +1633C/T) and cancer risk through a systematic review and meta-analysis. Potential source of heterogeneity was sought out through sensitivity analysis. Desirable data were extracted and registered into databases. Finally, a total of ten publications comprising of 22 case-control studies, including 4,259 cases and 7,006 controls were ultimately eligible for the meta-analysis. No significant association was uncovered for all the five polymorphisms and the overall cancer risk. However, in the stratification analysis by cancer type, a significantly decreased risk of hepatocellular carcinoma was identified for rs2227306 polymorphism (T vs C: odds ratio [OR] =0.721, 95% confidence interval [CI] =0.567-0.916, Pz =0.007; TT vs CC: OR =0.447, 95% CI =0.274-0.728, Pz =0.001; TT vs TC + CC: OR =0.480, 95% CI =0.304 0.760, Pz =0.002). In conclusion, our data shows that rs2227306 polymorphism plays a protective role in hepatocellular carcinoma risk. Future well-designed studies with a larger sample size are warranted to verify our findings. PMID- 27382311 TI - The evolution of combined molecular targeted therapies to advance the therapeutic efficacy in melanoma: a highlight of vemurafenib and cobimetinib. AB - Metastatic melanoma is an aggressive, rapidly progressive disease which historically had very few effective treatment options. However, since 2011, the therapeutic landscape of melanoma has undergone a dramatic transformation with two distinct approaches and has catalyzed the successful advancement in the clinical field of immuno-oncology. In addition, the recognition of a key oncogenic driver mutation in melanoma, BRAF, stimulated the development of multiple potent kinase inhibitors which has also influenced the expansion and use of targeted agents in the practice of oncology. Vemurafenib, the initial BRAF inhibitor approved for the treatment of melanoma, was the first agent to demonstrate rapid clinical responses and significantly improved survival which was a clinical breakthrough in the treatment of melanoma. Although exciting and practice changing, the unparalleled responses with vemurafenib are usually not sustained. Further investigations delineated several mechanisms of acquired resistance which are most often mediated by the upregulation of the MAPK pathway. MEK inhibitors, another class of small-molecule inhibitors, were developed as an alternative agent to suppress the MAPK pathway downstream, independent from BRAF activation. Multiple studies have demonstrated the improvement in antitumor activity when MEK inhibitors are used in combination with BRAF inhibitors in the treatment of metastatic melanoma. This is a review of the investigations that led to the US Food and Drug Administration approval in 2015 of the combination of vemurafenib and cobimetinib, adding to the quickly growing armament for the treatment of advanced or metastatic melanoma with a BRAF V600 mutation. PMID- 27382312 TI - Small interfering RNA targeting S100A4 sensitizes non-small-cell lung cancer cells (A549) to radiation treatment. AB - OBJECTIVE: This study aimed to investigate the impact of S100A4-small interfering RNA (S100A4-siRNA) on apoptosis and enhanced radiosensitivity in non-small-cell lung cancer (A549) cells. We also explored the mechanisms of radiosensitization and identified a new target to enhance radiosensitivity and gene therapy for non small-cell lung cancer. METHODS: RNA interference is a powerful tool for gene silencing. In this study, we constructed an effective siRNA to knock down S100A4. A549 cells were randomly divided into three groups: blank, negative control, and S100A4-siRNA. To investigate the effect of S100A4-siRNA, the expression of S100A4, E-cadherin, and p53 proteins and their messenger RNA (mRNA) was detected by Western blot and quantitative real-time polymerase chain reaction. Transwell chambers were used to assess cell invasion. Cell cycle and apoptosis were analyzed by flow cytometry. Radiosensitivity was determined by colony formation ability. RESULTS: Our results demonstrate that S100A4-siRNA effectively silenced the S100A4 gene. When siRNA against S100A4 was used, S100A4 protein expression was downregulated, whereas the expressions of E-cadherin and p53 were upregulated. In addition, a clear reduction in S100A4 mRNA levels was noted compared with the blank and negative control groups, whereas E-cadherin and p53 mRNA levels increased. Transfection with S100A4-siRNA significantly reduced the invasiveness of A549 cells. S100A4 silencing induced immediate G2/M arrest in cell cycle studies and increased apoptosis rates in A549 cells. In clonogenic assays, we used a multitarget, single-hit model to detect radiosensitivity after S100A4 knockdown. All parameters (D0, Dq, alpha, beta) indicated that the downregulation of S100A4 enhanced radiosensitivity in A549 cells. Furthermore, S100A4-siRNA upregulated p53 expression, suggesting that S100A4 may promote A549 cell proliferation, invasion, and metastasis by regulating the expression of other proteins. Therefore, siRNA-directed S100A4 knockdown may represent a viable clinical therapy for lung cancer. CONCLUSION: S100A4 downregulation potentially enhances the sensitivity of human A549 cells to radiotherapy. PMID- 27382313 TI - In vitro-activated tumor-specific T lymphocytes prolong the survival of patients with advanced gastric cancer: a retrospective cohort study. AB - BACKGROUND: Conventional tumor managements have limited survival benefits and cause severely impaired immune function in patients with advanced gastric cancer (GC) whereas immunotherapies could restore antitumor immunity. This prospective cohort study was aimed at investigating the efficacy of in vitro-activated tumor specific T lymphocytes combined with chemotherapy on the survival of patients with advanced GC. PATIENTS AND METHODS: Two hundred and seventy-four postoperative patients were enrolled in this study to receive either activated T lymphocytes immunotherapy combining chemotherapy (71 patients) or only receive postoperative chemotherapy (203 patients). Overall survival was analyzed by the Kaplan-Meier with log-rank test and Cox's regression methods. RESULTS: The immunotherapy prolonged 9.8-month median survival for advanced gastric cancer (29.70 vs 19.70 months, P=0.036). Furthermore, immunotherapy significantly benefited the survival of patients who underwent radical, palliative resection, and stage III malignancy. No serious adverse effect was observed in the immunotherapy group. CONCLUSION: In vitro-activated tumor-specific T lymphocytes prolonged survival in patients with advanced GC. PMID- 27382314 TI - Percutaneous microwave ablation combined with synchronous transcatheter arterial chemoembolization for the treatment of colorectal liver metastases: results from a follow-up cohort. AB - BACKGROUND: The purpose of this study was to retrospectively evaluate the therapeutic efficacy and safety of ultrasound-guided percutaneous microwave ablation (MWA) combined with synchronous transcatheter arterial chemoembolization (TACE) in patients with colorectal liver metastases (CRLM). PATIENTS AND METHODS: A retrospective analysis was performed in 30 patients who were treated with ultrasound-guided percutaneous MWA combined with synchronous TACE for colorectal cancer liver metastases from November 2011 to December 2014 in Zhongshan Hospital, Fudan University. The response of the tumor to treatment was evaluated by follow-up computed tomography and/or magnetic resonance imaging. Local tumor control, procedure-related complications, and long-term survival data were analyzed. RESULTS: A total of 30 patients with 43 tumors ranging in size from 1.4 cm to 10.0 cm were analyzed. The patients' mean age was 61.6+/-10.3 years (range, 44.0-78.0 years). The median follow-up time was 26.5+/-10.4 months (range, 13.3 50.6 months). The complete ablation rate was 81.4% (35/43 lesions) for CRLM. Complete response was achieved in eight cases (26.7%), and partial response was achieved in 17 cases (56.7%) 1 month after the procedure. The objective response rate (complete response + partial response) was 83.4%. Progression-free survival and overall survival were 5.0 months and 11.0 months, respectively. The 12-month and 24-month survival rates were 46.7% and 25.4%, respectively. A total of 22 patients succumbed during follow-up due to tumor progression. No major complications or perioperative mortalities were recorded. CONCLUSION: Ultrasound guided percutaneous MWA combined with synchronous TACE therapy is a safe and effective modality for patients with CRLM. PMID- 27382315 TI - Prognostic significance of metastatic lymph node ratio in squamous cell carcinoma of the cervix. AB - PURPOSE: Metastatic lymph node ratio (MLNR) was reported to be an important prognostic factor in several tumors. However, depth of primary tumor invasion is also important in cervical cancer prognostic analysis. In this study, the objective was to determine if MLNR can be used to define a high-risk category of patients with squamous cell carcinoma of the cervix (SCC). And we combined MLNR and depth of invasion to investigate whether prognosis of SCC can be predicted better. PATIENTS AND METHODS: We performed a retrospective review of patients with SCC who underwent radical hysterectomy and pelvic lymphadenectomy at QiLu Hospital of Shandong University from January 2007 to December 2009. Prognostic factors for disease-free survival (DFS) and overall survival (OS) were identified by univariate and multivariate analyses. RESULTS: One hundred and ninety-eight patients met the inclusion criteria and were included in the analysis. By cut point survival analysis, MLNR cutoff was designed as 0.2. On multivariate analysis, an MLNR >0.2 was associated with a worse OS (hazard ratio [HR] =2.560, 95% CI 1.275-5.143, P=0.008) and DFS (HR =2.404, 95% CI 1.202-4.809, P=0.013). Depth of invasion cutoff was designed as invasion >1/2 cervix wall and was associated with a worse OS (HR =1.806, 95% CI 1.063-3.070, P=0.029) and DFS (HR =1.900, 95% CI 1.101-3.279, P=0.021). In addition, subgroup analysis revealed significant difference in OS and DFS rates between different MLNR categories within the same depth of invasion category (P<0.05), however, not between different depth of invasion categories within the same MLNR category (P>0.05). CONCLUSION: MLNR may be used as the independent prognostic parameter in patients with SCC. Combined MLNR and depth of invasion can predict both OS and DFS better in SCC than one factor. Besides, MLNR appears to be a better prognostic value than depth of invasion for SCC. PMID- 27382316 TI - Expression of CD40 is a positive prognostic factor of diffuse large B-cell lymphoma treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). AB - OBJECTIVES: The objective of this study was to investigate the expression level of CD40 and its role in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) who were treated with rituximab-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). DESIGN AND METHODS: The immunohistochemical expressions of CD40 in 186 well-characterized DLBCL patients were evaluated by tissue microarrays, thereby revealing the relationship of the molecule CD40 with known tumor, patient-related variables, and survival rates. RESULTS: The results showed that CD40 expressions were not statistically different between the germinal center B-cell-like (GCB) type and the non-GCB type. We also analyzed the relationships of CD40 expression with overall survival (OS) and progression-free survival (PFS) in DLBCL patients who were uniformly treated with R-CHOP. A low expression of CD40 compared to high expression is related to poor OS and PFS. CONCLUSION: Our findings indicate that the CD40 level at onset acts as an independent prognostic predictor of DLBCL patients treated with R-CHOP. PMID- 27382317 TI - Training and administration of epinephrine auto-injectors for anaphylaxis treatment in US schools: results from the EpiPen4Schools((r)) pilot survey. AB - BACKGROUND: Anaphylaxis is a serious, potentially life-threatening condition. Adequate preparation for anaphylaxis management is imperative for school personnel. This descriptive pilot study assessed preparedness of US schools to manage anaphylactic reactions. METHODS: An exploratory, cross-sectional, web based, pilot survey assessed the occurrence and characteristics of anaphylactic events, as well as training provided to school personnel for the recognition and treatment of anaphylaxis. Eligible US schools were participants in the EpiPen4Schools((r)) program during the 2013-2014 school year. EpiPen4Schools provides EpiPen((r)) (epinephrine injection) Auto-Injectors and training materials to qualifying US schools. Survey data were parsed by US Census Bureau region and state and were evaluated using descriptive statistics. RESULTS: Schools from all 50 states and the District of Columbia participated in the survey (N=6,019). Among schools that provided information on anaphylactic events, 11% (607/5,683) reported the occurrence of one or more events, with significant variability in incidence across census regions and among states. A total of 5,613 schools provided information regarding which staff members were trained to recognize the signs and symptoms of anaphylaxis. Thirty-six percent of schools (2,022/5,613) indicated that only the school nurse and select staff were trained in anaphylaxis recognition. The proportion of schools in which most or all school staff received such training differed by region/state (range, 13%-100%). A total of 5,578 schools provided information on which staff were permitted to administer epinephrine. The majority of schools (54%; 3,024/5,578) permitted only the school nurse and select staff to administer epinephrine, although percentages varied by region/state (range, 4%-100%). CONCLUSION: Schools differed substantially in their preparedness to manage anaphylaxis, with significant disparities in staff training and permission to treat. Given the ramifications of delayed treatment, removing barriers to the recognition and treatment of anaphylactic events in schools is an important public health goal. PMID- 27382318 TI - Is the routine use of bevacizumab in the treatment of women with advanced or recurrent cancer of the cervix sustainable? AB - BACKGROUND: New chemotherapy combinations are being tested for the treatment of women with advanced, persistent or recurrent cervical cancer. We sought to evaluate the cost effectiveness of some newer combination therapies in cervical cancer. PATIENTS AND METHODS: A cost effectiveness decision model was used to analyze Gynecologic Oncology Group 240. All regimens were modeled for seven cycles. The regimens studied are as follows: regimen 1, cisplatin/paclitaxel (CP); regimen 2, CP with bevacizumab (CP+B); regimen 3, paclitaxel/topotecan (PT); and regimen 4, PT with bevacizumab (PT+B). Overall survival, cost, and complications were studied. Sensitivity analyses were performed. RESULTS: Mean chemotherapy costs over mean total costs for seven cycles of each follows: CP $571/$32,966; CP+B $61,671/$96,842; PT $9,211/$71,620; and PT+B $70,312/$109,211. Incremental cost-effectiveness ratio (ICER) for CP+B was $133,559/quality adjusted life year (QALY). ICER for PT+B was $124,576/QALY. To achieve an incremental ICER for CP+B:CP of <$50,000/QALY gained, the mean overall survival has to increase from 1.1 years with CP to 3.5 years with CP+B. An ICER <$50,000/QALY for the other regimens would take a survival of >10 years for PT and 4.1 years for PT+B. Treating 1,000 women with cervical cancer with CP+B would cost almost double the cost of treating >18,000 women with ovarian cancer annually (carboplatin/paclitaxel). CONCLUSION: CP is the most cost effective regimen. A 12-month increase in overall survival will not even make the newer combinations cost effective. Currently, the use of bevacizumab is not sustainable at today's costs. PMID- 27382319 TI - A structured review of health utility measures and elicitation in advanced/metastatic breast cancer. AB - BACKGROUND: Health utilities are increasingly incorporated in health economic evaluations. Different elicitation methods, direct and indirect, have been established in the past. This study examined the evidence on health utility elicitation previously reported in advanced/metastatic breast cancer and aimed to link these results to requirements of reimbursement bodies. METHODS: Searches were conducted using a detailed search strategy across several electronic databases (MEDLINE, EMBASE, Cochrane Library, and EconLit databases), online sources (Cost-effectiveness Analysis Registry and the Health Economics Research Center), and web sites of health technology assessment (HTA) bodies. Publications were selected based on the search strategy and the overall study objectives. RESULTS: A total of 768 publications were identified in the searches, and 26 publications, comprising 18 journal articles and eight submissions to HTA bodies, were included in the evidence review. Most journal articles derived utilities from the European Quality of Life Five-Dimensions questionnaire (EQ-5D). Other utility measures, such as the direct methods standard gamble (SG), time trade-off (TTO), and visual analog scale (VAS), were less frequently used. Several studies described mapping algorithms to generate utilities from disease-specific health related quality of life (HRQOL) instruments such as European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Breast Cancer 23 (EORTC QLQ-BR23), Functional Assessment of Cancer Therapy - General questionnaire (FACT-G), and Utility-Based Questionnaire Cancer (UBQ-C); most used EQ-5D as the reference. Sociodemographic factors that affect health utilities, such as age, sex, income, and education, as well as disease progression, choice of utility elicitation method, and country settings, were identified within the journal articles. Most submissions to HTA bodies obtained utility values from the literature rather than exploring the HRQOL data obtained during clinical development. This was critiqued by the National Institute for Health and Clinical Excellence (NICE). Furthermore, the impact of age on utilities was highlighted by NICE and it was suggested that an age match of the study population should be attempted. CONCLUSION: Health utilities are recorded across the globe to varying extents and using differing elicitation methods. Manufacturers seeking reimbursement need to be aware of the country specific requirements for elicitation of health utilities. PMID- 27382321 TI - Biosimilars: potential implications for clinicians. AB - With the expiration of patent protection for several biologics looming, the production of highly similar therapeutic agents has begun to emerge on the pharmaceutical market. These alternative drugs are referred to as biosimilars. Many anticipate that the introduction of these agents will result in a reduction in health care costs, which may create a more affordable biopharmaceutical market and also improve patient access. In contrast to generics, which are exact copies of their original products, biosimilars are not identical to their reference products. Due to concern about the safety and efficacy of biosimilars, separate regulatory approval pathways have been developed and implemented by several countries, including the US and Europe. Europe has led the way in acceptance of biosimilars into mainstream clinical practice. Biosimilars are not generic products and require extensive clinical and nonclinical bioequivalence studies before receiving marketing approval. Not only is there a lengthy developmental process, but also they will likely be required to have postmarketing surveillance and ongoing safety monitoring to keep track of issues that may arise, such as immunogenicity. Although US Food and Drug Administration approved the first biosimilar product in March 2015, physicians remain unfamiliar about their indications. PMID- 27382320 TI - Fatty acid desaturase 1 knockout mice are lean with improved glycemic control and decreased development of atheromatous plaque. AB - Delta-5 desaturase (D5D) and delta-6 desaturase (D6D), encoded by fatty acid desaturase 1 (FADS1) and FADS2 genes, respectively, are enzymes in the synthetic pathways for omega3, omega6, and omega9 polyunsaturated fatty acids (PUFAs). Although PUFAs appear to be involved in mammalian metabolic pathways, the physiologic effect of isolated D5D deficiency on these pathways is unclear. After generating >4,650 knockouts (KOs) of independent mouse genes and analyzing them in our high-throughput phenotypic screen, we found that Fads1 KO mice were among the leanest of 3,651 chow-fed KO lines analyzed for body composition and were among the most glucose tolerant of 2,489 high-fat-diet-fed KO lines analyzed by oral glucose tolerance test. In confirmatory studies, chow- or high-fat-diet-fed Fads1 KO mice were leaner than wild-type (WT) littermates; when data from multiple cohorts of adult mice were combined, body fat was 38% and 31% lower in Fads1 male and female KO mice, respectively. Fads1 KO mice also had lower glucose and insulin excursions during oral glucose tolerance tests along with lower fasting glucose, insulin, triglyceride, and total cholesterol levels. In additional studies using a vascular injury model, Fads1 KO mice had significantly decreased femoral artery intima/media ratios consistent with a decreased inflammatory response in their arterial wall. Based on this result, we bred Fads1 KO and WT mice onto an ApoE KO background and fed them a Western diet for 14 weeks; in this atherogenic environment, aortic trees of Fads1 KO mice had 40% less atheromatous plaque compared to WT littermates. Importantly, PUFA levels measured in brain and liver phospholipid fractions of Fads1 KO mice were consistent with decreased D5D activity and normal D6D activity. The beneficial metabolic phenotype demonstrated in Fads1 KO mice suggests that selective D5D inhibitors may be useful in the treatment of human obesity, diabetes, and atherosclerotic cardiovascular disease. PMID- 27382322 TI - Results from in vitro and ex vivo skin aging models assessing the antiglycation and anti-elastase MMP-12 potential of glycylglycine oleamide. AB - BACKGROUND: Glycation is an aging reaction of naturally occurring sugars with dermal proteins. Type I collagen and elastin are most affected by glycation during intrinsic chronological aging. AIM: To study the in vitro and ex vivo assays in human skin cells and explants and the antiaging effects of glycylglycine oleamide (GGO). MATERIALS AND METHODS: The antiglycation effect of GGO was assessed in a noncellular in vitro study on collagen and, ex vivo, by immunohistochemical staining on human skin explants (elastin network glycation). The ability of GGO to contract fibroblasts was assessed in a functional assay, and its anti-elastase (MMP-12) activity was compared to that of oleic acid alone, glycylglycine (GG) alone, and oleic acid associated with GG. RESULTS: In vitro, GGO reduced the glycation of type I collagen. Ex vivo, GGO restored the expression of fibrillin-1 inhibited by glycation. Furthermore, GGO induced a tissue retraction of almost 30%. Moreover, the MMP-12 activity was inhibited by up to 60%. CONCLUSION: Under the present in vitro and ex vivo conditions, GGO prevents glycation of the major structural proteins of the dermis, helping to reduce the risk of rigidification. By maintaining the elastic function of the skin, GGO may be a promising sparring partner for other topical antiaging agents. PMID- 27382323 TI - Efficacy of the low FODMAP diet for treating irritable bowel syndrome: the evidence to date. AB - This review summarizes the published clinical studies concerning the management of irritable bowel syndrome (IBS) using restriction of Fermentable Oligosaccharide, Disaccharide, Monosaccharide, and Polyols in the diet (low FODMAP diet). In recent years, the data supporting low FODMAP diet for the management of IBS symptoms have emerged, including several randomized controlled trials, case-control studies, and other observational studies. Unlike most dietary manipulations tried in the past to alleviate gastrointestinal symptoms of IBS, all studies on low FODMAP diet have consistently shown symptomatic benefits in the majority of patients with IBS. However, dietary adherence by the patients and clear dietary intervention led by specialized dietitians appear to be vital for the success of the diet. Up to 86% of patients with IBS find improvement in overall gastrointestinal symptoms as well as individual symptoms such as abdominal pain, bloating, constipation, diarrhea, abdominal distention, and flatulence following the diet. FODMAP restriction reduces the osmotic load and gas production in the distal small bowel and the proximal colon, providing symptomatic relief in patients with IBS. Long-term health effects of a low FODMAP diet are not known; however, stringent FODMAP restriction is not recommended owing to risks of inadequate nutrient intake and potential adverse effects from altered gut microbiota. In conclusion, the evidence to date strongly supports the efficacy of a low FODMAP diet in the treatment of IBS. Further studies are required to understand any potential adverse effects of long-term restriction of FODMAPs. PMID- 27382324 TI - Gastroesophageal reflux disease symptoms in the Greek general population: prevalence and risk factors. AB - BACKGROUND AND AIMS: Population-based data regarding the prevalence of gastroesophageal reflux disease (GERD) in Greece are very poor. This study estimated the prevalence of GERD symptoms and their risk factors in the Greek adult population. METHODS: A self-administered questionnaire was answered by a randomly selected population of 340 subjects. The question regarding "heartburn, chest pain, indigestion, or stomach acid coming up" as included in the Reflux Symptom Index was used for prevalence assessment. RESULTS: The monthly prevalence of GERD symptoms was found to be 52.0% in the Greek general population, with no statistically significant difference between the two sexes (P>0.05). The age group of 65-79 years showed a higher prevalence rate of GERD. Symptom severity was found to be mild (59.3%) or moderate (27.1%). The number of cigarettes smoked daily (but not smoking duration) as well as the number of alcoholic drinks consumed daily (but not the duration of alcohol drinking) were found to be related to GERD symptoms. No reported concomitant disease or medication was found to be related with GERD symptoms. CONCLUSION: The prevalence of GERD symptoms in the Greek general population was found to be 52.0%. Tobacco smoking and alcohol drinking but not concomitant disease or medications were found to be related with GERD symptoms. PMID- 27382325 TI - Association of tumor necrosis factor-alpha and -beta gene polymorphisms in inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) is a complex, multifactorial, chronic inflammatory disorder of the gastrointestinal tract in which immune dysregulation caused by genetic and/or environmental factors plays an important role. The aim of this case-control study was to evaluate the association of tumor necrosis factor-alpha (TNF-alpha) (308) and -beta (+252) polymorphisms with susceptibility of IBD. A total of 379 Saudi subjects including 179 IBD patients (ulcerative colitis (UC) =84 and Crohn's disease (CD) =95) and 200 age- and sex-matched healthy controls were recruited. TNF-alpha and TNF-beta genes were amplified using an amplification refractory mutation systems polymerase chain reaction methodology to detect TNF-alpha (-308) and -beta (+252) polymorphisms. The frequency of the GA genotype of TNF-alpha (-308G/A) was higher, and the frequencies of the GG and AA genotypes were significantly lower in IBD patients compared with those in controls, indicating that genotype GA-positive individuals are susceptible to IBD and that the GG and AA genotypes exert a protective effect. The frequency of allele A of TNF-alpha (-308G/A) was significantly higher and that of allele G was lower in IBD patients compared with those in controls, indicating an association of allele A with IBD risk in Saudi patients. On stratification of IBD patients into UC and CD, an almost similar pattern was noticed in both the groups. The results of TNF-beta (+252A/G) polymorphisms showed a significant increase in the frequency of the GG genotype in IBD patients, suggesting a positive association of GG genotype with IBD risk. On stratification of IBD patients into UC and CD, the genotype GG of TNF-beta was associated with susceptibility risk to UC but not CD. The frequencies of alleles and genotypes of both TNF-alpha and-beta polymorphisms are not affected by sex or type of IBD (familial or sporadic). TNF-alpha (-308G/A) and TNF-beta (+252A/G) polymorphisms are associated with risk of developing IBD in Saudi population. PMID- 27382326 TI - The clinicopathological features of sinonasal angiomatous polyps. AB - BACKGROUND: Sinonasal angiomatous polyp (SAP) is a rare subtype of sinonasal polyp that might be misdiagnosed as a malignant lesion due to its clinical symptoms. METHODS: We retrospectively enrolled the patients who were diagnosed with SAP in our hospital during 2008-2015. We analyzed the clinical symptoms, radiological findings, and pathological features of all patients diagnosed with SAP. RESULTS: Unilateral nasal obstruction, rhinorrhea, and epistaxis were the common symptoms. SAPs all originated from maxillary sinus and extended to nasal cavity with or without involving the nasopharynx. Expansile mass with surrounding bony destruction is typical on computed tomography imaging but specific for SAPs. The magnetic resonance revealed high signal intensity on T1-weighted images and hypointense rim on T2-weighted images. CONCLUSION: Computed tomography and magnetic resonance together might give rise to more accurate diagnosis of SAP. Incisional biopsy does help if the clinician suspects a malignant lesion. To treat SAP, complete removal is the optimal choice. PMID- 27382327 TI - Ketofol for monitored anesthesia care in shoulder arthroscopy and labral repair: a case report. AB - A 21-year-old male (body mass index: 28.3) with a history of asthma and reactive airway disease since childhood underwent left shoulder arthroscopy and labral repair surgery under monitored anesthesia care. Because the procedure was performed in the beach chair position, access to the patient's airway was limited throughout. To avoid general anesthesia and to limit potential complications associated with monitored anesthesia care, a ketofol admixture was used. This case demonstrates that, in conjunction with regional anesthesia, ketofol may be an acceptable alternative to propofol for maintenance in outpatient orthopedic procedures. PMID- 27382328 TI - Unraveling the confusion behind hyaluronic acid efficacy in the treatment of symptomatic knee osteoarthritis. AB - Hyaluronic acid (HA) is a commonly prescribed treatment for knee pain resulting from osteoarthritis (OA). Although numerous HA products have been approved for use by the US Food and Drug Administration, the efficacy of HA injections for knee OA remains disputed with meta-analyses and societal clinical guidelines drawing disparate conclusions. The American Academy of Orthopaedic Surgeons (AAOS) recently published a best-evidence systematic review and concluded that available data did not support the routine use of HA for knee OA. The purpose of the current article is to highlight issues that confound interpretation of meta analyses on HA for knee OA, to provide realistic estimates of the true efficacy of HA injections in knee OA, and to provide commentary on the methods and conclusions from the AAOS systematic review. In general, the clinical benefit of HA is underestimated using conventional meta-analytic techniques. When accounting for differential control group effects in HA studies, it can be reasonably concluded that HA injections may be beneficial to an appreciable number of patients with knee OA. In addition, the systematic review methodology used by AAOS was questionable due to exclusion of numerous relevant studies and inclusion of studies that used HAs not approved for use in the US, both of which underestimated the true efficacy of HA injections. Overall, the efficacy of HA injections for knee OA is likely better than previously reported. Future clinical trials and meta-analyses should account for differential control group effects in order to avoid the continued confusion surrounding HA injection efficacy. PMID- 27382329 TI - Challenges of pain control and the role of the ambulatory pain specialist in the outpatient surgery setting. AB - Ambulatory surgery is on the rise, with an unmet need for optimum pain control in ambulatory surgery centers worldwide. It is important that there is a proportionate increase in the availability of acute pain-management services to match the rapid rise of clinical patient load with pain issues in the ambulatory surgery setting. Focus on ambulatory pain control with its special challenges is vital to achieve optimum pain control and prevent morbidity and mortality. Management of perioperative pain in the ambulatory surgery setting is becoming increasingly complex, and requires the employment of a multimodal approach and interventions facilitated by ambulatory surgery pain specialists, which is a new concept. A focused ambulatory pain specialist on site at each ambulatory surgery center, in addition to providing safe anesthesia, could intervene early once problematic pain issues are recognized, thus preventing emergency room visits, as well as readmissions for uncontrolled pain. This paper reviews methods of acute pain management in the ambulatory setting with risk stratification, the utilization of multimodal interventions, including pharmacological and nonpharmacological options, opioids, nonopioids, and various routes with the goal of preventing delayed discharge and unexpected hospital admissions after ambulatory surgery. Continued research and investigation in the area of pain management with outcome studies in acute surgically inflicted pain in patients with underlying chronic pain treated with opioids and the pattern and predictive factors for pain in the ambulatory surgical setting is needed. PMID- 27382330 TI - Neuromuscular blockade in the elderly patient. AB - Neuromuscular blockade is a desirable or even essential component of general anesthesia for major surgical operations. As the population continues to age, and more operations are conducted in the elderly, due consideration must be given to neuromuscular blockade in these patients to avoid possible complications. This review considers the pharmacokinetics and pharmacodynamics of neuromuscular blockade that may be altered in the elderly. Compartment distribution, metabolism, and excretion of drugs may vary due to age-related changes in physiology, altering the duration of action with a need for reduced dosage (eg, aminosteroids). Other drugs (atracurium, cisatracurium) have more reliable duration of action and should perhaps be considered for use in the elderly. The range of interpatient variability that neuromuscular blocking drugs may exhibit is then considered and drugs with a narrower range, such as cisatracurium, may produce more predictable, and inherently safer, outcomes. Ultimately, appropriate neuromuscular monitoring should be used to guide the administration of muscle relaxants so that the risk of residual neuromuscular blockade postoperatively can be minimized. The reliability of various monitoring is considered. This paper concludes with a review of the various reversal agents, namely, anticholinesterase drugs and sugammadex, and the alterations in dosing of these that should be considered for the elderly patient. PMID- 27382331 TI - Tampa Scale of Kinesiophobia for Heart Turkish Version Study: cross-cultural adaptation, exploratory factor analysis, and reliability. AB - PURPOSE: Individuals with cardiac problems avoid physical activity and exercise because they expect to feel shortness of breath, dizziness, or chest pain. Assessing kinesiophobia related to heart problems is important in terms of cardiac rehabilitation. The Tampa Scale of Kinesiophobia Swedish Version for the Heart (TSK-SV Heart) is reliable and has been validated for cardiac diseases in the Swedish population. The aim of this study was to investigate the reliability, parallel-form validity, and exploratory factor analysis of the TSK for the Heart Turkish Version (TSK Heart Turkish Version) for evaluating kinesiophobia in patients with heart failure and pulmonary arterial hypertension. METHODS: This cross-sectional study involved translation, back translation, and cross-cultural adaptation (localization). Forty-three pulmonary arterial hypertension and 32 heart failure patients were evaluated using the TSK Heart Turkish Version. The 17 item scale, originally composed for the Swedish population, has four factors: perceived danger for heart problem, avoidance of exercise, fear of injury, and dysfunctional self. Cronbach's alpha (internal consistency) and exploratory factor analysis were used to assess the questionnaire's reliability. Results of the patients in the 6-minute walk test, International Physical Activity Questionnaire, and Nottingham Health Profile were analyzed by Pearson's correlation analysis with the TSK Heart Turkish Version to indicate the convergent validity. RESULTS: Cronbach's alpha for the TSK Heart Turkish Version was 0.75, indicating acceptable internal consistency. Although exploratory factor analysis showed a different subgroup distribution than the original questionnaire, the model was acceptable for the four-factor model hypothesis. Therefore, the questionnaire was rated as reliable. CONCLUSION: These results supported the reliability of the TSK Heart Turkish Version. Since the acceptable four-factor model fits the subgroups and measures of reliability are sufficiently high, the questionnaire seems reliable for pulmonary arterial hypertension and heart failure patients. PMID- 27382332 TI - Fosaprepitant dimeglumine for the management of chemotherapy-induced nausea and vomiting: patient selection and perspectives. AB - Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of antineoplastic agents. Several treatment regimens are used to address this problem. Fosaprepitant is a neurokinin-1 receptor blocker used in the prevention and treatment of CINV, especially for moderately and severely emetogenic chemotherapy. It is highly effective in the treatment of delayed CINV. Data from previous studies show that fosaprepitant is noninferior to aprepitant in the management of CINV. Fosaprepitant is given as a single-dose intravenous infusion, thus offering better patient compliance. The dose-limiting side effect of fosaprepitant is an infusion-related reaction, ranging from pain at the infusion site to thrombophlebitis. This side effect has been reported with coadministration of anthracycline agents. PMID- 27382333 TI - Rate of bleeding-related episodes in adult patients with primary immune thrombocytopenia: a retrospective cohort study using a large administrative medical claims database in the US. AB - BACKGROUND: Immune thrombocytopenia (ITP) is a rare disorder characterized by low platelet counts and an increased tendency to bleed. The goal of ITP therapy is to treat or prevent bleeding. Actual rates of bleeding are unknown. Clinical trial data may not reflect real-world bleeding rates because of the inclusion of highly refractory patients and more frequent use of rescue therapy. METHODS: We used administrative medical claims data in the US to examine the occurrence of bleeding-related episodes (BREs) - a composite end point including bleeding and/or rescue therapy use - in adults diagnosed with primary ITP (2008-2012). BRE rates were calculated overall and by ITP phase and splenectomy status. Patients were followed from ITP diagnosis until death, disenrollment from the health plan, or June 30, 2013, whichever came first. RESULTS: We identified 6,651 adults diagnosed with primary ITP over the study period (median age: 53 years; 59% female). During 13,064 patient-years of follow-up, 3,768 patients (57%) experienced >=1 BRE (1.08 BREs per patient-year; 95% confidence interval: 1.06 1.10). The majority (58%) of BREs consisted of rescue therapy use only. Common bleeding types were gastrointestinal hemorrhage, hematuria, ecchymosis, and epistaxis. Intracranial hemorrhage was reported in 74 patients (1%). Just over 7% of patients underwent splenectomy. Newly diagnosed and splenectomized patients had elevated BRE rates. CONCLUSION: We provide current real-world estimates of BRE rates in adults with primary ITP. The majority of ITP patients experienced >=1 BRE, and over half were defined by rescue therapy use alone. This demonstrates the importance of examining both bleeding and rescue therapy use to fully assess disease burden. PMID- 27382335 TI - Retropupillary iris-claw intraocular lens in ectopia lentis in Marfan syndrome. AB - OBJECTIVE: To report visual outcomes, complication rate, and safety of retropupillary iris-claw intraocular lens (ICIOL) in ectopia lentis in Marfan syndrome (MFS). DESIGN: Retrospective study. METHODS: Six eyes of three MFS patients with ectopia lentis underwent surgery for subluxation lens and retropupillary ICIOL implantation from October 2014 to October 2015 at the Department of Ophthalmology, Santa Maria Hospital in Lisbon, Portugal. Demographics, preoperative and postoperative best-corrected visual acuity (BCVA), and intraocular pressure were evaluated. Endothelium cell count was assessed using specular microscopy; anterior chamber depth was measured using Pentacam postoperatively; and intraocular lens position was viewed by ultrasound biomicroscopy. All patients were female; mean age was 20+/-14.264 years (range: 7 38 years). RESULTS: The average follow-up period was 6.66 months (range: 4-16 months). Preoperative BCVA was 0.568+/-0.149 logMAR units, and postoperative BCVA was 0.066+/-0.121 logMAR units. The mean BCVA gain was -0.502+/-0.221 on the logMAR scale. Postoperative average astigmatism and intraocular pressure were 1.292+/-0.697 mmHg (range: 0.5-2.25 mmHg) and 16 mmHg (range: 12-18 mmHg), respectively. The average endothelial cell density decreased from 3,121+/-178 cells/mm(2) before surgery to 2,835+/-533 cells/mm(2) after surgery (measured at last follow-up visit) and in the last follow-up, representing an average endothelial cell loss of 9.16%. Mean anterior chamber depth was 4.01 mm (+/-0.77 mm), as measured by Pentacam. No complications were found intra- or postoperatively in any of the six studied eyes. CONCLUSION: Retropupillary ICIOL implantation is a safe and effective procedure in the treatment of aphakia in MFS eyes, without capsular support after surgery for ectopia lens. The six eyes that underwent lensectomy and retropupillary ICIOL implantation have had excellent visual outcomes with no complications so far. PMID- 27382336 TI - Upper eyelid granuloma: a rare delayed-onset complication secondary to cosmetic filler injection on forehead. AB - A 72-year-old Taiwanese woman had the history of cosmetic cryopreserved autologous fat injection on her forehead ~21 years ago and was referred to our oculoplastic clinic and presented with multiple painless mass, which she had for 4 years, on both upper eyelids. Histopathology confirmed the diagnosis of foreign body granuloma on both upper eyelids. Clinicians should be aware of the potential complication of granuloma reaction and migration even many years after the injection. We advise that autologous fat injection should be performed solely by trained physicians and it should be made known that there is a possible occurrence of migration. PMID- 27382334 TI - Contralateral prophylactic mastectomy: current perspectives. AB - There has been an increasing trend in the use of contralateral prophylactic mastectomy (CPM) in the United States among women diagnosed with unilateral breast cancer, particularly young women. Approximately one-third of women <40 years old are undergoing CPM in the US. Most studies have shown that the CPM trend is mainly patient-driven, which reflects a changing environment for newly diagnosed breast cancer patients. The most common reason that women choose CPM is based on misperceptions about CPM's effect on survival and overestimation of their contralateral breast cancer (CBC) risk. No prospective studies have shown survival benefit to CPM, and the CBC rate for most women is low at 10 years. Fear of recurrence is also a big driver of CPM decisions. Nonetheless, studies have shown that women are mostly satisfied with undergoing CPM, but complications and subsequent surgeries with reconstruction have been associated with dissatisfaction with CPM. Studies on surgeon's perspectives on CPM are sparse but show that the most common reasons surgeons discuss CPM with patients is because of a suspicious family history or for a patient who is a confirmed BRCA mutation carrier. Studies on the cost-effectiveness of CPM have been conflicting and are highly dependent on patient's quality of life after CPM. Most recent guidelines for CPM are contradictory. Future areas of research include the development of interventions to better inform patients about CPM, modification of the guidelines to form a more consistent statement, longer term studies on CBC risk and CPM's effect on survival, and prospective studies that track the psychosocial effects of CPM on body image and sexuality. PMID- 27382337 TI - A randomized, double-blind, placebo-, and positive-controlled clinical pilot study to evaluate the efficacy and tolerability of standardized aqueous extracts of Terminalia chebula and Terminalia bellerica in subjects with hyperuricemia. AB - OBJECTIVES: To evaluate the efficacy and tolerability of standardized aqueous extracts of Terminalia chebula and Terminalia bellerica versus febuxostat and placebo on reduction in serum uric acid levels in subjects with hyperuricemia. MATERIALS AND METHODS: A total of 110 eligible subjects with hyperuricemia were enrolled and randomized to either of the five treatment groups - T. chebula 500 mg twice a day (BID), T. bellerica 250 mg BID, T. bellerica 500 mg BID, placebo BID, and febuxostat 40 mg once daily plus an identical placebo - for a duration of 24 weeks. Serum uric acid levels were measured at baseline and at the end of 4, 8, 12, 16, 20, and 24 weeks. Statistical analysis was done using GraphPad Prism Software 4. RESULTS AND INTERPRETATION: All active treatment groups showed a reduction in serum uric acid levels compared to baseline and placebo. Significant reduction in mean serum uric acid levels started as early as 4 weeks following treatment, compared to baseline, with T. bellerica (500 and 250 mg), febuxostat (P<0.001), and T. chebula 500 mg (P<0.01); an increase in serum uric acid levels was seen with placebo (P<0.05). The serum uric acid levels became steady after 16 weeks of treatment and remained the same until the end of 24 weeks. The reduction of serum uric acid levels in the T. bellerica 500 mg group was nearly twice that of the T. chebula 500 mg group as well as T. bellerica 250 mg group at all time points. T. bellerica 500 mg reduced serum uric acid levels from 8.07+/-0.87 to 5.78+/-0.25 compared to febuxostat, which reduced serum uric acid levels from 8.53+/-0.97 to 4.28+/-0.67 (P<0.001) at the end of 24 weeks. The efficacy of T. bellerica appeared to be dose dependent. All the formulations were well tolerated. CONCLUSION: T. bellerica has the potential for treating hyperuricemia as it was devoid of any serious adverse effects in the present study. Further studies are needed to confirm this potential. PMID- 27382339 TI - Three-dimensional needle-tip localization by electric field potential and camera hybridization for needle electromyography exam robotic simulator. AB - As one of neurological tests, needle electromygraphy exam (NEE) plays an important role to evaluate the conditions of nerves and muscles. Neurology interns and novice medical staff need repetitive training to improve their skills in performing the exam. However, no training systems are able to reproduce multiple pathological conditions to simulate real needle electromyogram exam. For the development of a robotic simulator, three components need to be realized: physical modeling of upper limb morphological features, position-dependent electromyogram generation, and needle localization; the latter is the focus of this study. Our idea is to couple two types of sensing mechanism in order to acquire the needle-tip position with high accuracy. One is to segment the needle from camera images and calculate its insertion point on the skin surface by a top hat transform algorithm. The other is voltage-based depth measurement, in which a conductive tissue-like phantom was used to realize both needle-tip localization and physical sense of needle insertion. For that, a pair of electrodes was designed to generate a near-linear voltage distribution along the depth direction of the tissue-like phantom. The accuracy of the needle-tip position was investigated by the electric field potential and camera hybridization. The results showed that the needle tip could be detected with an accuracy of 1.05+/ 0.57 mm. PMID- 27382338 TI - The treatment of type 2 diabetes in the presence of renal impairment: what we should know about newer therapies. AB - Worldwide, an estimated 200 million people have chronic kidney disease (CKD), the most common causes of which include hypertension, arteriosclerosis, and diabetes. Importantly, ~40% of patients with diabetes develop CKD, yet evidence from major multicenter randomized controlled trials shows that intensive blood glucose control through pharmacological intervention can reduce the incidence and progression of CKD. Standard therapies for the treatment of type 2 diabetes include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin. While these drugs have an important role in the management of type 2 diabetes, only the thiazolidinedione pioglitazone can be used across the spectrum of CKD (stages 2-5) and without dose adjustment; there are contraindications and dose adjustments required for the remaining standard therapies. Newer therapies, particularly dipeptidyl peptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors, are increasingly being used in the treatment of type 2 diabetes; however, a major consideration is whether these newer therapies can also be used safely and effectively across the spectrum of renal impairment. Notably, reductions in albuminuria, a marker of CKD, are observed with many of the drug classes. Dipeptidyl peptidase-IV inhibitors can be used in all stages of renal impairment, with appropriate dose reduction, with the exception of linagliptin, which can be used without dose adjustment. No dose adjustment is required for liraglutide, albiglutide, and dulaglutide in CKD stages 2 and 3, although all glucagon-like peptide-1 receptor agonists are currently contraindicated in stages 4 and 5 CKD. At stage 3 CKD or greater, the sodium-glucose cotransporter-2 inhibitors (dapagliflozin, canagliflozin, and empagliflozin) either require dose adjustment or are contraindicated. Ongoing trials, such as CARMELINA, MARLINA, CREDENCE, and CANVAS R, will help determine the position of these new therapy classes and if they have renoprotective effects in patients with CKD. PMID- 27382341 TI - Transarterial chemoembolization with drug-eluting beads versus conventional transarterial chemoembolization in locally advanced hepatocellular carcinoma. AB - PURPOSE: In hepatocellular carcinoma patients with large or multinodal tumors, where curative treatment options are not feasible, transarterial therapies play a major role. Transarterial chemoembolization (TACE) with drug-eluting beads (DEB TACE) is a promising new approach due to higher intratumoral and lower systemic concentration of the chemotherapeutic agent compared to conventional TACE (cTACE). PATIENTS AND METHODS: In a retrospective analysis, 32 patients with hepatocellular carcinoma who received either DEB or a cTACE were compared regarding survival time, disease recurrence, and side effects such as pain and fever. RESULTS: No significant differences could be detected between the cTACE and DEB-TACE groups with regard to mean hospital stay, appearance of postinterventional fever, or 30-day mortality. However, the application of intravenous analgesics as postinterventional pain medication was needed more often in patients treated with DEB-TACE (57.1% vs 12.5%, P=0.0281). The overall median survival after the initial procedure was 10.8 months in the cTACE group and 9.2 months in the DEB-TACE group, showing no significant difference. CONCLUSION: No survival benefit for patients treated with either DEB-TACE or cTACE was observed. Surprisingly, a higher rate of postinterventional pain could be detected after DEB-TACE. PMID- 27382340 TI - Fractional exhaled nitric oxide-measuring devices: technology update. AB - The measurement of exhaled nitric oxide (NO) has been employed in the diagnosis of specific types of airway inflammation, guiding treatment monitoring by predicting and assessing response to anti-inflammatory therapy and monitoring for compliance and detecting relapse. Various techniques are currently used to analyze exhaled NO concentrations under a range of conditions for both health and disease. These include chemiluminescence and electrochemical sensor devices. The cost effectiveness and ability to achieve adequate flexibility in sensitivity and selectivity of NO measurement for these methods are evaluated alongside the potential for use of laser-based technology. This review explores the technologies involved in the measurement of exhaled NO. PMID- 27382342 TI - Contributions of sociodemographic factors to criminal behavior. AB - We explored the extent to which prisoner sociodemographic variables (age, education, marital status, employment, and whether their parents were married or not) influenced offending in 64 randomly selected Brunei inmates, comprising both sexes. A quantitative field survey design ideal for the type of participants used in a prison context was employed to investigate the problem. Hierarchical multiple regression analysis with backward elimination identified prisoner marital status and age groups as significantly related to offending. Furthermore, hierarchical multinomial logistic regression analysis with backward elimination indicated that prisoners' age, primary level education, marital status, employment status, and parental marital status as significantly related to stealing offenses with high odds ratios. All 29 nonrecidivists were false negatives and predicted to reoffend upon release. Similarly, all 33 recidivists were projected to reoffend after release. Hierarchical binary logistic regression analysis revealed age groups (24-29 years and 30-35 years), employed prisoner, and primary level education as variables with high likelihood trends for reoffending. The results suggested that prisoner interventions (educational, counseling, and psychotherapy) in Brunei should treat not only antisocial personality, psychopathy, and mental health problems but also sociodemographic factors. The study generated offending patterns, trends, and norms that may inform subsequent investigations on Brunei prisoners. PMID- 27382343 TI - Insights into workplace bullying: psychosocial drivers and effective interventions. AB - Research on effectiveness of workplace bullying interventions has lagged behind descriptive studies on this topic. The literature on bullying intervention research has only recently expanded to a point that allows for synthesis of findings across empirical studies. This study addresses the question of whether workplace bullying can be reduced in prevalence and consequences, if so to what extent and by which strategies and interventions. It opens with a brief overview of the nature of bullying at work and discussion of some precursors and existing interventions. However, its principal focus is on the findings obtained from selected (quasi-) experimental longitudinal studies on antibullying interventions, drawing together the results of studies conducted in Europe, USA, and Australia, including several economic sectors, and concerned about primary, secondary, and tertiary prevention programs and strategies. Additional emphasis is considered from the psychosocial drivers highlighted both from prescriptive and cross-sectional studies and factual empirical studies. One randomized control study and seven quasiexperimental longitudinal studies were identified by searching electronic databases and bibliographies and via contact with experts. The majority of outcomes evidenced some level of change, mostly positive, suggesting that workplace bullying interventions are more likely to affect knowledge, attitudes, and self-perceptions, but actual bullying behaviors showed much more mixed results. In general, growing effectiveness was stated as the level of intervention increased from primary to tertiary prevention. However, methodological problems relating to the evaluation designs in most studies do not allow direct attribution of these findings to the interventions. Overall, the evaluation of antibullying interventions must flourish and be improved, requiring close cooperation between practitioners and academics to design, implement, and evaluate effective interventions based on grounded theoretical and methodological approaches. Finally, this systematic review highlights future directions for enhancing the adoption, high-quality implementation, and dissemination of evidence-based workplace bullying prevention and intervention programs. PMID- 27382344 TI - Are doctors risk takers? AB - OBJECTIVE: Risk taking affects human behavior in general and decisions in medicine in particular. We used game theory to assess physicians' risk-taking tendencies. METHODS: Physicians were recruited to the study by advertisement. It was explained that they would receive a sum of money for correct prediction of the flipping of a coin. They could try to sell their opportunity to flip the coin for an amount of money they determined. The sum offered by the participants was considered an indicator of risk taking. A demographic questionnaire assessed age, sex, seniority, and area of specialization of the participants. A multivariate analysis assessed associations between risk-taking behavior and, seniority, and specialization. RESULTS: Sixty-two physicians participated, 36 males and 26 females, seniority 1-34 years. Of a possible range of 0-10, the mean score for risk taking was 5.5 - just slightly more than indifference. Negative correlations were found between risk taking and seniority, and between risk taking and age (beta =-0.45, P<0.001 for both). Surgeons and anesthesiologists showed greater risk taking than did other physicians (beta =0.69, P<0.05); and females less than males, though the latter correlation was not statistically significant. CONCLUSION: Understanding the tendency of physicians to risk taking may elucidate their decision-making processes and contribute to understanding of causes of adverse events and to the education of physicians. PMID- 27382345 TI - Sex-specific sleep patterns among university students in Lebanon: impact on depression and academic performance. AB - Good sleep quality and quantity are fundamental to the maintenance of normal physiological processes. Changes in sleep patterns are commonly observed among young adults and are shown to impact neurocognitive, academic, and psychological well-being. Given the scarcity of sleep information about Lebanon and acknowledging the sex differences in various sleep dimensions, we conducted a study that aimed at assessing sex differences in sleep habits among university students in Lebanon in relation to psychoacademic status. A total of 540 students (50.6% females) completed a questionnaire that inquired about sociodemographics and evaluated sleep quality and depression using the Pittsburg Sleep Quality Index (PSQI) and Center for Epidemiological Studies Depression Scale (CES-D), respectively. The mean PSQI global score (6.57+/-3.49) indicated poor sleep, with no significant differences between men and women. The sleep/wake rhythm was delayed on weekends for both sexes. Females exhibited earlier bedtimes and rise times and longer sleep durations on both weekdays and weekends. However, unlike males females showed a greater phase delay in wake times than bedtimes on weekends (149 minutes vs 74 minutes, respectively). In all, 70.9% of females suffered from depressive symptoms, which was a significantly higher proportion compared with 58.5% of males (P<0.01). Based on the mean cumulative self-reported grade point average (GPA), the academic performance of females was significantly better than that of males (2.8+/-0.61 vs 2.65+/-0.61, P<0.05, respectively). Depression, as scored by CES-D, in females was significantly negatively correlated with the cumulative GPA (r=-0.278, P<0.01), earlier wake time (r= 0.168, P<0.05), and average sleep duration (r=-0.221, P<0.01) on weekdays. GPA of males was significantly correlated with bedtime on weekends (r=-0.159, P<0.05). We conclude that sex differences in sleep timing, such as bedtime/rise time and nocturnal sleep duration, rather than sleep quality exist among Lebanese university students. Sex-specific sleep patterns have differential impact on psychological and academic well-being. PMID- 27382346 TI - Cultural adaptation: translatability assessment and linguistic validation of the patient-reported outcome instrument for irritable bowel syndrome with diarrhea. AB - BACKGROUND AND OBJECTIVE: Following a 2009 US Food and Drug Administration guidance, a new patient-reported outcome (PRO) instrument was developed to support end points in multinational clinical trials assessing irritable bowel syndrome with diarrhea (IBS-D) symptom severity. Our objective was to assess the translatability of the IBS-D PRO instrument into ten languages, and subsequently perform a cultural adaptation/linguistic validation of the questionnaire into Japanese and US Spanish. MATERIALS AND METHODS: Translatability assessments of the US English version of the IBS-D PRO were performed by experienced PRO translators who were native speakers of each target language and currently residing in target-language countries. Languages were Chinese (People's Republic of China), Dutch (the Netherlands), French (Belgium), German (Germany), Japanese (Japan), Polish (Poland), Portuguese (Brazil), Russian (Russia), Spanish (Mexico), and Spanish (US). The project team assessed the instrument to identify potential linguistic and/or cultural adaptation issues. After the issues identified were resolved, the instrument was translated into Spanish (US) and Japanese through a process of two forward translations, one reconciled translation, and one backward translation. The project team reviewed the translated versions before the instruments were evaluated by cognitive debriefing interviews with samples of five Spanish (US) and five Japanese IBS-D patients. RESULTS: Linguistic and cultural adaptation concerns identified during the translatability assessment required minor revisions, mainly the presentation of dates/times and word structure. During the cognitive debriefing interviews, two of five Spanish respondents misunderstood the term "bowel movement" to mean only diarrhea in the Spanish version. Consequently, the term was changed from "movimiento intestinal" to "evacuaciones". None of the Japanese respondents identified issues with the Japanese version. CONCLUSION: The translatability of the IBS-D PRO instrument into ten target languages was confirmed, with only minor changes made to the translations of the instrument. The translation and linguistic validation into Spanish (US) and Japanese provide evidence that this instrument can be used in multinational trials and clinical settings. PMID- 27382347 TI - Potential role of a new PEGylated recombinant factor VIII for hemophilia A. AB - Hemophilia A, a deficiency in the activity of coagulation factor (F) VIII, is an X-linked bleeding disorder with an approximate incidence of one in 5,000 male infants. Bleeding-related complications often result in greater severity of disease, poor quality of life, surgical interventions for severe joint destruction, and shortened life span. With the availability of plasma-derived and recombinant FVIII products, the benefits of primary prophylaxis were demonstrated and is now the standard of care for patients with severe factor deficiencies. Current hemophilia research is focusing on the creation of new factor replacement therapies with longer half-lives; accessing alternative mechanisms to achieve desired hemostasis and enhance bypassing activity; and limiting the immunogenicity of the protein. PEGylation involves the covalent attachment of polyethylene glycol (PEG) to a protein, peptide, or a small molecule drug. PEG effectively increases the molecular weight and size of the protein by creating a hydrophilic cloud around the molecule. This molecular change may reduce susceptibility of the molecule to proteolytic activity and degradation. It is also believed that PEGylation changes the surface charge of the protein that ultimately interferes with some receptor-mediated clearance processes. The half life of PEGylated factor is more prolonged when compared to non-PEGylated full length recombinant FVIII. The dawn of a new era in the care of hemophilia patients is upon us with the release of recombinant FVIII products with extended half-lives, and products with even more extended half-life will become available in a very short time. With all the promise of these new agents, many questions still remain. PMID- 27382348 TI - Resveratrol attenuates lipopolysaccharide-induced dysfunction of blood-brain barrier in endothelial cells via AMPK activation. AB - Resveratrol, a phytoalexin, is reported to activate AMP-activated protein kinase (AMPK) in vascular cells. The blood-brain barrier (BBB), formed by specialized brain endothelial cells that are interconnected by tight junctions, strictly regulates paracellular permeability to maintain an optimal extracellular environment for brain homeostasis. The aim of this study was to elucidate the effects of resveratrol and the role of AMPK in BBB dysfunction induced by lipopolysaccharide (LPS). Exposure of human brain microvascular endothelial cells (HBMECs) to LPS (1 ug/ml) for 4 to 24 hours week dramatically increased the permeability of the BBB in parallel with lowered expression levels of occluding and claudin-5, which are essential to maintain tight junctions in HBMECs. In addition, LPS significantly increased the reactive oxygen species (ROS) productions. All effects induced by LPS in HBVMCs were reversed by adenoviral overexpression of superoxide dismutase, inhibition of NAD(P) H oxidase by apocynin or gain-function of AMPK by adenoviral overexpression of constitutively active mutant (AMPK-CA) or by resveratrol. Finally, upregulation of AMPK by either AMPK-CA or resveratrol abolished the levels of LPS-enhanced NAD(P)H oxidase subunits protein expressions. We conclude that AMPK activation by resveratrol improves the integrity of the BBB disrupted by LPS through suppressing the induction of NAD(P)H oxidase-derived ROS in HBMECs. PMID- 27382349 TI - Effect of edaravone in diabetes mellitus-induced nephropathy in rats. AB - Edaravone, a synthetic-free radical scavenger, has been reported to reduce ischemia-reperfusion-induced renal injury by improving tubular cell function, and lowering serum creatinine and renal vascular resistance. The present study investigated the effect of edaravone in diabetes mellitus-induced nephropathy in rats. A single administration of streptozotocin (STZ, 55 mg/kg, i.p.) was employed to induce diabetes mellitus in rats. The STZ-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Mean body weight, lipid alteration, renal functional and histopathology were analysed. Diabetic rats developed nephropathy as evidenced by a significant increase in serum creatinine and urea, and marked renal histopathological abnormalities like glomerulosclerosis and tubular cell degeneration. The kidney weight to body weight ratio was increased. Moreover, diabetic rats showed lipid alteration as evidenced by a signifi cant increase in serum triglycerides and decrease in serum high-density lipoproteins. Edaravone (10 mg/kg, i.p., last 4-weeks) treatment markedly prevented the development of nephropathy in diabetic rats by reducing serum creatinine and urea and preventing renal structural abnormalities. In addition, its treatment, without significantly altering the elevated glucose level in diabetic rats, prevented diabetes mellitus-induced lipid alteration by reducing serum triglycerides and increasing serum high-density lipoproteins. Interestingly, the renoprotective effect of edaravone was comparable to that of lisinopril (5 mg/kg, p.o, 4 weeks, standard drug). Edaravone prevented renal structural and functional abnormalities and lipid alteration associated with experimental diabetes mellitus. Edaravone has a potential to prevent nephropathy without showing an anti-diabetic action, implicating its direct renoprotection in diabetic rats. PMID- 27382350 TI - The effect of progesterone and 17-beta estradiol on membrane-bound HLA-G in adipose derived stem cells. AB - Membrane-bound HLA-G (mHLA-G) discovery on adipose derived stem cells (ADSCs) as a tolerogenic and immunosuppressive molecule was very important. Many documents have shown that HLA-G expression can be controlled via some hormones such as progesterone (P4) and estradiol (E2). Therefore, this study was designed to evaluate progesterone and estradiol effects on mHLA-G in ADSCs at restricted and combination concentrations. Three independent cell lines were cultured in complete free phenol red DMEM and subcultured to achieve suffi cient cells. These cells were treated with P4, E2 and P4 plus E2 at physiologic and pregnancy concentrations for 3 days in cell culture conditions. The HLA-G positive ADSCs was measured via monoclonal anti HLA-G-FITC/MEMG-09 by means of flow cytometry in nine groups. Data were analyzed by one way ANOVA and Tukey's post hoc tests. There were no signifi cant values of the mean percentage of HLA-G positive cells in E2-treated and the combination of P4 plus E2-treated ADSCs compared to control cells (p value>0.05) but P4 had a signifi cant increase on mHLA-G in ADSCs (p value<0.05). High P4 concentration increased mHLA-G but E2 and the combination of P4 plus E2 could not change mHLA-G on ADSCs. PMID- 27382351 TI - Cryptotanshinone inhibits TNF-alpha-induced LOX-1 expression by suppressing reactive oxygen species (ROS) formation in endothelial cells. AB - Cryptotanshinone (CPT) is a natural compound isolated from traditional Chinese medicine Salvia miltiorrhiza Bunge. In the present study, the regulatory effect and potential mechanisms of CPT on tumor necrosis factor alpha (TNF-alpha) induced lectin-like receptor for oxidized low density lipoprotein (LOX-1) were investigated. Human umbilical vein endothelial cells (HUVECs) were cultured and the effect of TNF-alpha on LOX-1 expression at mRNA and protein levels was determined by Real-time PCR and Western blotting respectively. The formation of intracellular ROS was determined with fluorescence probe CM-DCFH2-DA. The endothelial ox-LDL uptake was evaluated with DiI-ox-LDL. The effect of CPT on LOX 1 expression was also evaluated with SD rats. TNF-alpha induced LOX-1 expression in a dose- and time-dependent manner in endothelial cells. TNF-alpha induced ROS formation, phosphorylation of NF-kappaB p65 and ERK, and LOX-1 expression, which were suppressed by rotenone, DPI, NAC, and CPT. NF-kappaB inhibitor BAY11-7082 and ERK inhibitor PD98059 inhibited TNF-alpha-induced LOX-1 expression. CPT and NAC suppressed TNF-alpha-induced LOX-1 expression and phosphorylation of NF kappaB p65 and ERK in rat aorta. These data suggested that TNF-alpha induced LOX 1 expression via ROS activated NF-kappaB/ERK pathway, which could be inhibited by CPT. This study provides new insights for the anti-atherosclerotic effect of CPT. PMID- 27382352 TI - Effects of systemic administration of ibuprofen on stress response in a rat model of post-traumatic stress disorder. AB - Pro-inflammatory cytokine and brain-derived neurotrophic factor (BDNF) are modulated in post-traumatic stress disorder (PTSD). This study investigated the effects of ibuprofen (IBU) on enhanced anxiety in a rat model of PTSD induced by a single prolonged stress (SPS) procedure. The effects of IBU on inflammation and BDNF modulation in the hippocampus and the mechanisms underlying for anxiolytic action of IBU were also investigated. Male Sprague-Dawley rats were given IBU (20 or 40 mg/kg, i.p., once daily) for 14 days. Daily IBU (40 mg/kg) administration signifi cantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index in the EPM test, and increased the time spent in the center of an open fi eld after SPS. IBU administration signifi cantly decreased the expression of pro-inflammatory mediators, such as tumor necrosis factor-alpha, interleukin-1beta, and BDNF, in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. These fi ndings suggest that IBU exerts a therapeutic effect on PTSD that might be at least partially mediated by alleviation of anxiety symptoms due to its anti-inflammatory activity and BDNF expression in the rat brain. PMID- 27382353 TI - Minimal systems analysis of mitochondria-dependent apoptosis induced by cisplatin. AB - Recently, it was reported that the role of mitochondria-reactive oxygen species (ROS) generating pathway in cisplatin-induced apoptosis is remarkable. Since a variety of molecules are involved in the pathway, a comprehensive approach to delineate the biological interactions of the molecules is required. However, quantitative modeling of the mitochondria-ROS generating pathway based on experiment and systemic analysis using the model have not been attempted so far. Thus, we conducted experiments to measure the concentration changes of critical molecules associated with mitochondrial apoptosis in both human mesothelioma H2052 and their rho(0) cells lacking mitochondrial DNA (mtDNA). Based on the experiments, a novel mathematical model that can represent the essential dynamics of the mitochondrial apoptotic pathway induced by cisplatin was developed. The kinetic parameter values of the mathematical model were estimated from the experimental data. Then, we have investigated the dynamical properties of this model and predicted the apoptosis levels for various concentrations of cisplatin beyond the range of experiments. From parametric perturbation analysis, we further found that apoptosis will reach its saturation level beyond a certain critical cisplatin concentration. PMID- 27382354 TI - Effects of analgesics and antidepressants on TREK-2 and TRESK currents. AB - TWIK-related K(+) channel-2 (TREK-2) and TWIK-related spinal cord K(+) (TRESK) channel are members of two-pore domain K(+) channel family. They are well expressed and help to set the resting membrane potential in sensory neurons. Modulation of TREK-2 and TRESK channels are involved in the pathogenesis of pain, and specifi c activators of TREK-2 and TRESK may be benefi cial for the treatment of pain symptoms. However, the effect of commonly used analgesics on TREK-2 and TRESK channels are not known. Here, we investigated the effect of analgesics on TREK-2 and TRESK channels. The effects of analgesics were examined in HEK cells transfected with TREK-2 or TRESK. Amitriptyline, citalopram, escitalopram, and fluoxetine significantly inhibited TREK-2 and TRESK currents in HEK cells (p<0.05, n=10). Acetaminophen, ibuprofen, nabumetone, and bupropion inhibited TRESK, but had no effect on TREK-2. These results show that all analgesics tested in this study inhibit TRESK activity. Further study is needed to identify the mechanisms by which the analgesics modulate TREK-2 and TRESK differently. PMID- 27382355 TI - Sequestration of sorcin by aberrant forms of tau results in the defective calcium homeostasis. AB - Neurofi brillary tangles (NFTs) of microtubule-associated protein tau are a pathological hallmark of Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress has been known to be involved in the pathogenesis of AD. However, the exact role of ER stress in tau pathology has not yet been clearly elucidated. In present study, the possible relationship between tau pathology and ER stress was examined in terms of sorcin, which is a calcium binding protein and plays an important role in calcium homeostasis. Our previous yeast two hybrid study showed that sorcin is a novel tau interacting protein. Caspase-3-cleaved tau (T4C3) showed significantly increased tau-sorcin interaction compared to wild type tau (T4). Thapsigargin-induced ER stress and co-expression of constitutively active GSK3beta (GSK3beta-S9A) also exhibited significantly increased tau-sorcin interactions. T4C3-expressing cells showed potentiated thapsigargin-induced apoptosis and disruption of intracellular calcium homeostasis compared to T4 expressing cells. Overexpression of sorcin signifi cantly attenuated thapsigargin induced apoptosis and disruption of calcium homeostasis. In contrary, siRNA mediated knock-down of sorcin showed significantly increased thapsigargin-induced apoptosis and disruption of calcium homeostasis. These data strongly suggest that sequestration of sorcin by aberrant forms of tau compromises the function of sorcin, such as calcium homeostasis and cellular resistance by ER stress, which may consequently result in the contribution to the progression of AD. PMID- 27382356 TI - Preventive effects of imperatorin on perfluorohexanesulfonate-induced neuronal apoptosis via inhibition of intracellular calcium-mediated ERK pathway. AB - Early life neuronal exposure to environmental toxicants has been suggested to be an important etiology of neurodegenerative disease development. Perfluorohexanesulfonate (PFHxS), one of the major perfluoroalkyl compounds, is widely distributed environmental contaminants. We have reported that PFHxS induces neuronal apoptosis via ERK-mediated pathway. Imperatorin is a furanocoumarin found in various edible plants and has a wide range of pharmacological effects including neuroprotection. In this study, the effects of imperatorin on PFHxS-induced neuronal apoptosis and the underlying mechanisms are examined using cerebellar granule cells (CGC). CGC were isolated from seven-day old rats and were grown in culture for seven days. Caspase-3 activity and TUNEL staining were used to determine neuronal apoptosis. PFHxS-induced apoptosis of CGC was significantly reduced by imperatorin and PD98059, an ERK pathway inhibitor. PFHxS induced a persistent increase in intracellular calcium, which was significantly blocked by imperatorin, NMDA receptor antagonist, MK801 and the L-type voltage-dependent calcium channel blockers, diltiazem and nifedipine. The activation of caspase-3 by PFHxS was also inhibited by MK801, diltiazem and nifedipine. PFHxS-increased ERK activation was inhibited by imperatorin, MK801, diltiazem and nifedipine. Taken together, imperatorin protects CGC against PFHxS induced apoptosis via inhibition of NMDA receptor/intracellular calcium-mediated ERK pathway. PMID- 27382357 TI - Involvement of spinal muscarinic and serotonergic receptors in the anti-allodynic effect of electroacupuncture in rats with oxaliplatin-induced neuropathic pain. AB - This study was performed to investigate whether the spinal cholinergic and serotonergic analgesic systems mediate the relieving effect of electroacupuncture (EA) on oxaliplatin-induced neuropathic cold allodynia in rats. The cold allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) was evaluated by immersing the rat's tail into cold water (4C) and measuring the withdrawal latency. EA stimulation (2 Hz, 0.3-ms pulse duration, 0.2~0.3 mA) at the acupoint ST36, GV3, or LI11 all showed a significant anti-allodynic effect, which was stronger at ST36. The analgesic effect of EA at ST36 was blocked by intraperitoneal injection of muscarinic acetylcholine receptor antagonist (atropine, 1 mg/kg), but not by nicotinic (mecamylamine, 2 mg/kg) receptor antagonist. Furthermore, intrathecal administration of M2 (methoctramine, 10 ug) and M3 (4-DAMP, 10 ug) receptor antagonist, but not M1 (pirenzepine, 10 ug) receptor antagonist, blocked the effect. Also, spinal administration of 5-HT3 (MDL-72222, 12 ug) receptor antagonist, but not 5-HT1A (NAN-190, 15 ug) or 5-HT2A (ketanserin, 30 ug) receptor antagonist, prevented the anti-allodynic effect of EA. These results suggest that EA may have a signifi cant analgesic action against oxaliplatin-induced neuropathic pain, which is mediated by spinal cholinergic (M2, M3) and serotonergic (5-HT3) receptors. PMID- 27382358 TI - Activating transcription factor-3 induction is involved in the anti-inflammatory action of berberine in RAW264.7 murine macrophages. AB - Berberine is an isoquinoline alkaloid found in Rhizoma coptidis, and elicits anti inflammatory effects through diverse mechanisms. Based on previous reports that activating transcription factor-3 (ATF-3) acts as a negative regulator of LPS signaling, the authors investigated the possible involvement of ATF-3 in the anti inflammatory effects of berberine. It was found berberine concentration dependently induced the expressions of ATF-3 at the mRNA and protein levels and concomitantly suppressed the LPS-induced productions of proinflammatory cytokines (TNF-alpha, IL-6, and IL-1beta). In addition, ATF-3 knockdown abolished the inhibitory effects of berberine on LPS-induced proinflammatory cytokine production, and prevented the berberine-induced suppression of MAPK phosphorylation, but had little effect on AMPK phosphorylation. On the other hand, the effects of berberine, that is, ATF-3 induction, proinflammatory cytokine inhibition, and MAPK inactivation, were prevented by AMPK knockdown, suggesting ATF-3 induction occurs downstream of AMPK activation. The in vivo administration of berberine to mice with LPS-induced endotoxemia increased ATF-3 expression and AMPK phosphorylation in spleen and lung tissues, and concomitantly reduced the plasma and tissue levels of proinflammatory cytokines. These results suggest berberine has an anti-inflammatory effect on macrophages and that this effect is attributable, at least in part, to pathways involving AMPK activation and ATF-3 induction. PMID- 27382359 TI - Facilitation of AMPA receptor-mediated steady-state current by extrasynaptic NMDA receptors in supraoptic magnocellular neurosecretory cells. AB - In addition to classical synaptic transmission, information is transmitted between cells via the activation of extrasynaptic receptors that generate persistent tonic current in the brain. While growing evidence supports the presence of tonic NMDA current (INMDA) generated by extrasynaptic NMDA receptors (eNMDARs), the functional significance of tonic INMDA in various brain regions remains poorly understood. Here, we demonstrate that activation of eNMDARs that generate INMDA facilitates the alpha-amino-3-hydroxy-5-methylisoxazole-4 proprionate receptor (AMPAR)-mediated steady-state current in supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs). In low-Mg(2+) artificial cerebrospinal fluid (aCSF), glutamate induced an inward shift in Iho lding (IGLU) at a holding potential (Vholding) of -70 mV which was partly blocked by an AMPAR antagonist, NBQX. NBQX-sensitive IGLU was observed even in normal aCSF at Vholding of -40 mV or -20 mV. IGLU was completely abolished by pretreatment with an NMDAR blocker, AP5, under all tested conditions. AMPA induced a reproducible inward shift in Iholding (IAMPA) in SON MNCs. Pretreatment with AP5 attenuated IAMPA amplitudes to ~60% of the control levels in low-Mg(2+) aCSF, but not in normal aCSF at Vholding of -70 mV. IAMPA attenuation by AP5 was also prominent in normal aCSF at depolarized holding potentials. Memantine, an eNMDAR blocker, mimicked the AP5-induced IAMPA attenuation in SON MNCs. Finally, chronic dehydration did not affect IAMPA attenuation by AP5 in the neurons. These results suggest that tonic INMDA, mediated by eNMDAR, facilitates AMPAR function, changing the postsynaptic response to its agonists in normal and osmotically challenged SON MNCs. PMID- 27382360 TI - Ahcyl2 upregulates NBCe1-B via multiple serine residues of the PEST domain mediated association. AB - Inositol-1,4,5-triphosphate [IP3] receptors binding protein released with IP3 (IRBIT) was previously reported as an activator of NBCe1-B. Recent studies have characterized IRBIT homologue S-Adenosylhomocysteine hydrolase-like 2 (AHCYL2). AHCYL2 is highly homologous to IRBIT (88%) and heteromerizes with IRBIT. The two important domains in the N-terminus of AHCYL2 are a PEST domain and a coiled-coil domain which are highly comparable to those in IRBIT. Therefore, in this study, we tried to identify the role of those domains in mouse AHCYL2 (Ahcyl2), and we succeeded in identifying PEST domain of Ahcyl2 as a regulation region for NBCe1-B activity. Site directed mutagenesis and coimmunoprecipitation assay showed that NBCe1-B binds to the N-terminal Ahcyl2-PEST domain, and its binding is determined by the phosphorylation of 4 critical serine residues (Ser151, Ser154, Ser157, and Ser160) in Ahcyl2 PEST domain. Also we revealed that 4 critical serine residues in Ahcyl2 PEST domain are indispensable for the activation of NBCe1-B using measurement of intracellular pH experiment. Thus, these results suggested that the NBCe1-B is interacted with 4 critical serine residues in Ahcyl2 PEST domain, which play an important role in intracellular pH regulation through NBCe1-B. PMID- 27382361 TI - Positive effect of HPV status on prognostic value of blood lymphocyte-to-monocyte ratio in advanced cervical carcinoma. AB - BACKGROUND: This retrospective study aimed to investigate the prognostic significance of pretreatment lymphocyte-to-monocyte ratio (LMR) in locally advanced cervical cancer and its effect on overall survival. METHODS: The usual blood routine test was quantitatively performed to detect LMR. Signal strengths of human papilloma virus (HPV) type DNA in detected cervical cancer samples using hybrid capture 2 were analyzed in relative light units (RLU) compared with 1 pg/mL of HPV type 16 DNA-positive control (RLU/PC) samples. A total of 1.0 RLU/PC (~1 pg/mL) was used as the threshold for a positive result. The HPV-positive specimens were typed using reverse-hybridization line probe assay. RESULTS: The LMR and HPV DNA were found to be independent prognostic markers for 5-year overall survival (OS) and progression-free survival, respectively. Their joint detection may further enhance the predictive value for OS. In the positive HR (high risk)-HPV DNA status subgroup, LMR had a positive effect on improved OS but not in the non-HR HPV DNA status subgroup. CONCLUSIONS: The LMR and HR-HPV DNA status can be identified as independent prognostic factors. The different influences of LMR in combined chemoradiotherapy on survival may be related to HR HPV DNA status. The combined detection of LMR and HR-HPV DNA status may contribute to screening prognosis. PMID- 27382362 TI - PCR Conditions for 16S Primers for Analysis of Microbes in the Colon of Rats. AB - The study of the composition of the intestinal flora is important to the health of the host, playing a key role in maintaining intestinal homeostasis and the evolution of the immune system. For these studies, various universal primers of the 16S rDNA gene are used in microbial taxonomy. Here, we report an evaluation of 5 universal primers to explore the presence of microbial DNA in colon biopsies preserved in RNAlater solution. The DNA extracted was used for the amplification of PCR products containing the variable (V) regions of the microbial 16S rDNA gene. The PCR products were studied by restriction fragment length polymorphism (RFLP) analysis and DNA sequence, whose percent of homology with microbial sequences reported in GenBank was verified using bioinformatics tools. The presence of microbes in the colon of rats was quantified by the quantitative PCR (qPCR) technique. We obtained microbial DNA from rat, useful for PCR analysis with the universal primers for the bacteria 16S rDNA. The sequences of PCR products obtained from a colon biopsy of the animal showed homology with the classes bacilli (Lactobacillus spp) and proteobacteria, normally represented in the colon of rats. The proposed methodology allowed the attainment of DNA of bacteria with the quality and integrity for use in qPCR, sequencing, and PCR-RFLP analysis. The selected universal primers provided knowledge of the abundance of microorganisms and the formation of a preliminary test of bacterial diversity in rat colon biopsies. PMID- 27382364 TI - Spectral Studies of UV and Solar Photocatalytic Degradation of AZO Dye and Textile Dye Effluents Using Green Synthesized Silver Nanoparticles. AB - The photocatalytic degradation of the chemical dye AZO and dye effluents in different time duration has been investigated using biologically synthesized silver nanoparticles. Dye industry effluents and AZO dye undergo degradation to form harmless intermediate and colourless products following irradiation by UV and solar light in the presence of green synthesized silver nanoparticles. The degree of degradation was tested under the experimental conditions such as P(H), temperature, and absorbance of the dye in UV and solar light was measured. The degradation was higher in the UV light source than in the solar light source. Green synthesized silver nanoparticles in the UV light source were found to expedite the dye degradation process. PMID- 27382363 TI - Quantitative proteomic analysis of histone modifications in decitabine sensitive and resistant leukemia cell lines. AB - BACKGROUND: The refractory nature of many cancers remains the main health challenge over the past century. The epigenetic drug, decitabine (DAC), represents one of the most promising therapeutic agents in cancers particularly in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, its ambiguous anti-tumor mechanism and the unpredictable drug-resistant nature in some population compromise its application in cancer therapy. In crosstalk with DNA methylation, histone post-translational modifications (PTMs) are the key players in modulating the downstream epigenetic status of tumor suppressor genes. This study targets the role of decitabine in epigenetic regulation in leukemia therapy and searches responsive predictors and therapeutic targets for pretreatment evaluation and drug development. RESULTS: A simple, fast, and robust proteomic strategy identified 15 novel PTMs and 60 PTM combinations in two leukemia cell lines (MDS-L and TF-1). Histone modification profiles have been generated and compared between DAC sensitive and resistant groups (n = 3) in response to DAC treatment. Among these histone PTMs, five of which were found differentially upon DAC treatment in drug sensitive and resistant cells: H3.3K36me3, H4K8acK12acK16ac in MDS-L cells; and H3.1K27me1, H3.1K36me1, H3.1K27me1K36me1 in TF-1 cells. They may serve as biomarkers in predicting leukemia and drug responsiveness. In addition, we also explored PTM differences in two cell lines which were developed from early and advanced stages of AML. Three PTMs (H3.1K27me3, H3.1K27me2K36me2 and H3.3K27me2K36me2) are highly abundant in TF-1 cells (advanced AML cell line), suggesting their relevance to leukemogenesis. Our method allowed deep analysis of histone proteins and elucidation of a large number of histone PTMs with high precision and sensitivity. CONCLUSION: DAC-induced DNA hypomethylation has wide impact on chromatin modifications. This study represents first effort to investigate the undefined epigenetic mechanism of decitabine in leukemia therapy. The identification of 15 novel PTMs and the discovery of several marks have relevance to epigenetic directed therapies. PMID- 27382365 TI - PPARgamma Agonists as an Anti-Inflammatory Treatment Inhibiting Rotavirus Infection of Small Intestinal Villi. AB - Rotavirus infection has been reported to induce an inflammatory response in the host cell accompanied by the increased expression or activation of some cellular molecules including ROS, NF-kappaB, and COX-2. PPARgamma stimulation and N acetylcysteine (NAC) treatment have been found to interfere with viral infections including rotavirus infection. Small intestinal villi isolated from in vivo infected mice with rotavirus ECwt were analyzed for the percentage of ECwt infected cells, the presence of rotavirus antigens, and infectious virion yield following treatment with pioglitazone. Isolated villi were also infected in vitro and treated with PPARgamma agonists (PGZ, TZD, RGZ, DHA, and ALA), all-trans retinoic acid (ATRA), and NAC. After treatments, the expression of cellular proteins including PPARgamma, NF-kappaB, PDI, Hsc70, and COX-2 was analyzed using immunochemistry, ELISA, immunofluorescence, and Western blotting. The results showed that rotavirus infection led to an increased accumulation of the cellular proteins studied and ROS. The virus infection-induced accumulation of the cellular proteins studied and ROS was reduced upon pioglitazone treatment, causing also a concomitant reduction of the infectious virion yield. We hypothesized that rotavirus infection is benefiting from the induction of a host cell proinflammatory response and that the interference of the inflammatory pathways involved leads to decreased infection. PMID- 27382366 TI - A Review of Surrogate Assisted Multiobjective Evolutionary Algorithms. AB - Multiobjective evolutionary algorithms have incorporated surrogate models in order to reduce the number of required evaluations to approximate the Pareto front of computationally expensive multiobjective optimization problems. Currently, few works have reviewed the state of the art in this topic. However, the existing reviews have focused on classifying the evolutionary multiobjective optimization algorithms with respect to the type of underlying surrogate model. In this paper, we center our focus on classifying multiobjective evolutionary algorithms with respect to their integration with surrogate models. This interaction has led us to classify similar approaches and identify advantages and disadvantages of each class. PMID- 27382367 TI - Formulation for Effective Screening and Management of Nonalcoholic Steatohepatitis: Noninvasive NAFLD Management Strategy. AB - To establish a versatile means for screening and management of nonalcoholic steatohepatitis (NASH), shear wave velocity was measured in 20 normal controls and 138 consecutive nonalcoholic fatty liver disease (NAFLD) cases. Referencing biochemical properties in 679 healthy volunteers, a formula to distinguish NASH suspects was established and validated in another cohort of 138 histologically proven NAFLD cases. NASH and simple steatosis (SS) suspects were selected based on a plot of shear wave velocity against age. A formula consisting of five factors (gamma-glutamyl transpeptidase, alkaline phosphatase, platelet counts, body mass index, and presence/absence of type 2 diabetes mellitus) distinguished NASH suspects from SS suspects with area under the receiver operating characteristic curve values of 86% and 84% in the development and validation cohorts. Among 25 NAFLD cases in which shear wave velocity was repeatedly measured, 8 and 9 cases revealed an increase or decrease, respectively, of shear wave velocity in the entire liver, and the corresponding change in shear wave velocity was primarily observed in the right lobe or the left lateral segment, respectively. These results suggest that the new formula and sequential shear wave velocity measurements at each segment enable high throughput screening of NASH suspects and noninvasive assessment of pathophysiological alleviation/aggravation in cases of NASH. PMID- 27382368 TI - Comparison of Medical Adhesive Tapes in Patients at Risk of Facial Skin Trauma under Anesthesia. AB - Introduction. Adhesive tapes are used for taping eyelids closed and securing endotracheal tubes during general anesthesia. These tapes can cause facial skin injury. We compared the incidence of facial skin injury and patient satisfaction with different tapes used. Methods. A total of 60 adult patients at risk of skin trauma were randomized to use 3MTM Kind Removal Silicone Tape or standard acrylate tapes: 3M Durapore (endotracheal tube) and Medipore (eyelids). Patients were blinded to tape used. Postoperatively, a blinded recovery nurse assessed erythema, edema, and denudation of skin. Anesthesiologist in charge also assessed skin injury. On postoperative day 1, patients rated satisfaction with the condition of their skin over the eyelids and face on a 5-point Likert scale. Results. More patients had denudation of skin with standard tapes, 4 (13.3%) versus 0 with silicone tape (p = 0.026) and in anesthesiologist-evaluated skin injury 11 (37%) with standard versus 1 (3%) with silicone (p = 0.002). No significant differences were found in erythema and edema. Patient satisfaction score was higher with silicone tape: over eyelids: mean 3.83 (standard) versus 4.53 (silicone), Mann-Whitney U test, p < 0.001; over face: mean 3.87 (standard) versus 4.57 (silicone) (p < 0.001). Conclusion. Silicone tape use had less skin injury and greater patient satisfaction than standard acrylate tapes. PMID- 27382369 TI - Changes in Pathological Complete Response Rates after Neoadjuvant Chemotherapy for Breast Carcinoma over Five Years. AB - Historically, neoadjuvant chemotherapy (NACT) was extrapolated from adjuvant regimens. Dual HER2 blockade and the introduction of carboplatin for triple negative breast cancers (TNBC) emerged by December 2013 and have improved pathological complete response (pCR) rates. The objective of this study was to assess the pCR rates before and after the introduction of these new neoadjuvant regimens. Materials and Methods. Stage I-III breast cancer patients who received NACT were analyzed for rates of pCR by clinical characteristics (i.e., age, BMI, axillary lymphadenopathy, and histologic subtype), by time period (1 = 3/2010 11/2013, 2 = 12/2013-3/2015), and by type of chemotherapy (e.g., anthracycline/taxane only, carboplatin-containing, and HER2 blockade). Results. 113 patients received NACT. Overall pCR rate was 26.5 percent (n = 30). The pCR rate increased from 14% to 43.1% (p = 0.001) from time period 1 to time period 2 and were associated with HER2 positivity (p = 0.003), receiving treatment during time period 2 (p = 0.001) and using an anthracycline/taxane plus additional agent type of regimen (p = 0.004). Conclusions. Our study revealed a significant difference in rates of pCR over five years. Window of opportunity trials and other trials that utilize pCR analysis should be encouraged. PMID- 27382370 TI - Manufacturing Cells for Clinical Use. PMID- 27382372 TI - Perceptions of the Role of Short-Term Volunteerism in International Development: Views from Volunteers, Local Hosts, and Community Members. AB - Background. Short-term international volunteer trips traditionally involve volunteers from high-income countries travelling to low- and middle-income countries to assist in service-related development activities. Their duration typically ranges from 7 to 90 days. The city of La Romana, Dominican Republic, receives hundreds of short-term international volunteers annually. They participate in activities aimed at improving conditions faced by a marginalized ethnic-Haitian community living in bateyes. Methods. This qualitative analysis examined perceptions of short-term international volunteerism, held by three key stakeholder groups in La Romana: local hosts, international volunteers, and community members. Responses from semistructured interviews were recorded and analysed by thematic analysis. Results. Themes from the 3 groups were broadly categorized into general perceptions of short-term volunteerism and proposed best practices. These were further subdivided into perceptions of value, harms, and motivations associated with volunteer teams for the former and best practices around volunteer composition and selection, partnership, and skill sets and predeparture training for the latter. Conclusion. Notable challenges were associated with short-term volunteering, including an overemphasis on the material benefits from volunteer groups expressed by community member respondents; misalignment of the desired and actual skill sets of volunteers; duplicate and uncoordinated volunteer efforts; and the perpetuation of stereotypes suggesting that international volunteers possess superior knowledge or skills. Addressing these challenges is critical to optimizing the conduct of short-term volunteerism. PMID- 27382371 TI - Cellular Reprogramming Using Defined Factors and MicroRNAs. AB - Development of human bodies, organs, and tissues contains numerous steps of cellular differentiation including an initial zygote, embryonic stem (ES) cells, three germ layers, and multiple expertized lineages of cells. Induced pluripotent stem (iPS) cells have been recently developed using defined reprogramming factors such as Nanog, Klf5, Oct3/4 (Pou5f1), Sox2, and Myc. This outstanding innovation is largely changing life science and medicine. Methods of direct reprogramming of cells into myocytes, neurons, chondrocytes, and osteoblasts have been further developed using modified combination of factors such as N-myc, L-myc, Sox9, and microRNAs in defined cell/tissue culture conditions. Mesenchymal stem cells (MSCs) and dental pulp stem cells (DPSCs) are also emerging multipotent stem cells with particular microRNA expression signatures. It was shown that miRNA-720 had a role in cellular reprogramming through targeting the pluripotency factor Nanog and induction of DNA methyltransferases (DNMTs). This review reports histories, topics, and idea of cellular reprogramming. PMID- 27382373 TI - Arsenic in Drinking Water and Lung Cancer Mortality in the United States: An Analysis Based on US Counties and 30 Years of Observation (1950-1979). AB - Background. To examine whether the US EPA (2010) lung cancer risk estimate derived from the high arsenic exposures (10-934 ug/L) in southwest Taiwan accurately predicts the US experience from low arsenic exposures (3-59 ug/L). Methods. Analyses have been limited to US counties solely dependent on underground sources for their drinking water supply with median arsenic levels of >=3 ug/L. Results. Cancer risks (slopes) were found to be indistinguishable from zero for males and females. The addition of arsenic level did not significantly increase the explanatory power of the models. Stratified, or categorical, analysis yielded relative risks that hover about 1.00. The unit risk estimates were nonpositive and not significantly different from zero, and the maximum (95% UCL) unit risk estimates for lung cancer were lower than those in US EPA (2010). Conclusions. These data do not demonstrate an increased risk of lung cancer associated with median drinking water arsenic levels in the range of 3-59 ug/L. The upper-bound estimates of the risks are lower than the risks predicted from the SW Taiwan data and do not support those predictions. These results are consistent with a recent metaregression that indicated no increased lung cancer risk for arsenic exposures below 100-150 ug/L. PMID- 27382374 TI - Exposures Resulting in Safety and Health Concerns for Child Laborers in Less Developed Countries. AB - Objectives. Worldwide, over 200 million children are involved in child labor, with another 20 million children subjected to forced labor, leading to acute and chronic exposures resulting in safety and health (S&H) risks, plus removal from formal education and play. This review summarized S&H issues in child labor, including forced or indentured domestic labor as other sectors of child labor. Specifically, we focused on exposures leading to S&H risks. Methods. We used PubMed, Scopus, Science Direct, and Google Scholar. References were in English, published in 1990-2015, and included data focused on exposures and S&H concerns of child labor. Results. Seventy-six journal articles were identified, 67 met criteria, 57 focused on individual countries, and 10 focused on data from multiple countries (comparing 3-83 countries). Major themes of concern were physical exposures including ergonomic hazards, chemical exposure hazards, and missed education. Childhood labor, especially forced, exploitative labor, created a significant burden on child development, welfare, and S&H. Conclusions. More field researche data emphasizing longitudinal quantitative effects of exposures and S&H risks are needed. Findings warranted developing policies and educational interventions with proper monitoring and evaluation data collection, plus multiple governmental, international organization and global economic reform efforts, particularly in lower-income, less developed countries. PMID- 27382375 TI - Reference values of clinical pathology parameters in cynomolgus monkeys (Macaca fascicularis) used in preclinical studies. AB - Nonhuman primates are increasingly used in biomedical research since they are highly homologous to humans compared to other rodent animals. However, there is limited reliable reference data of the clinical pathology parameters in cynomolgus monkeys, and in particular, only some coagulation and urinalysis parameters have been reported. Here, we reported the reference data of clinical chemical, hematological, blood coagulation, and urinalysis parameters in cynomolgus monkeys. The role of sex differences was analyzed and several parameters (including hematocrit, hemoglobin, red blood cell, blood urea nitrogen, total bilirubin, alkaline phosphatase, creatinine kinase, gamma glutamyl tranferase, and lactate dehydrogenase) significantly differed between male and female subjects. In addition, compared to previous study results, lactate dehydrogenase, creatinine kinase, and aspartate aminotransferase showed significant variation. Interstudy differences could be affected by several factors, including age, sex, geographic origin, presence/absence of anesthetics, fasting state, and the analytical methods used. Therefore, it is important to deliberate with the overall reference indices. In conclusion, the current study provides a comprehensive and updated reference data of the clinical pathology parameters in cynomolgus monkeys and provides improved assessment criteria for evaluating preclinical studies or biomedical research. PMID- 27382376 TI - Antimicrobial activity of essential oil of Eucalyptus globulus against fish pathogenic bacteria. AB - The antibacterial activities of the essential oil of Eucalyptus globulus (EOEG) was determined against 7 fish pathogenic bacteria (Edwardsiella tarda, Streptococcus iniae, S. parauberis, Lactococcus garviae, Vibrio harveyi, V. ichthyoenteri and Photobacterium damselae) obtained from farmed olive flounder. The inhibitory activity was evaluated by three methods: Disc diffusion method, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). According to the disc diffusion test, as the concentration of EOEG (5-40 ug) rises, the inhibitory zone increases in size. Compared with amoxicillin, tetracycline and chloramphenicol, EOEG showed similar antibacterial activity. The MIC of EOEG ranged from 7.8 to 125 mg/mL and MBC values ranged from 62 to 250 mg/mL. These results show that EOEG has antimicrobial activity against all seven bacteria, but there was no marked difference between each genus. From these results, it is suggested that EOEG can be used as an antimicrobial agent against fish bacterial diseases in the fish industry. PMID- 27382377 TI - Anti-inflammatory effect of egg white-chalcanthite and purple bamboo salts mixture on arthritis induced by monosodium iodoacetate in Sprague-Dawley rats. AB - The aim of this study is to investigate the potential of anti-osteoarthritis effects on egg white-chalcanthite (EC), purple bamboo salts (PBS), and a mixture of EC and PBS (EC+PBS). EC is a mixture of egg white and pulverized chalcanthite. PBS has been widely used as one of functional foods in Korea and shows unique features compared with common salt. Osteoarthritis was induced by intra-articular injection of monosodium iodoacetate (MIA, 4mg/kg bw) in Sprague-Dawley (SD) rats. Test substances were administered once daily for 6 weeks at doses of 10 mg EC, EC+100 mg PBS, EC+200 mg PBS before and after MIA injection. Each substance was assessed by blood chemistry parameters, and by serum cytokines including IL-1beta and IL-6, and nitric oxide (NO) and prostaglandin-E2 (PGE2). Structural changes of articular cartilage were also evaluated by histopathological examination. As a result, body weight and blood chemistry parameter were not different in all experimental groups. EC+PBS mixture reduced the production of PGE2, NO, IL-1beta, and IL-6. In histological grade of osteoarthritis, EC+PBS mixture had a tendency to ameliorate damage of articular cartilage induced by MIA in a dose-dependent manner. In conclusion, EC+PBS mixture was demonstrated to have a potential for anti-inflammatory effect against osteoarthritis induced by MIA in a dose dependent manner. PMID- 27382378 TI - Anti-Helicobacter pylori activity of crude N-acetylneuraminic acid isolated from glycomacropeptide of whey. AB - Helicobacter pylori colonizes the gastric mucosa of about half of the world's population, causing chronic gastritis and gastric cancer. An increasing emergence of antibiotic-resistant H. pylori arouses demand on alternative non-antibiotic based therapies. In this study, we freshly prepared crude N-acetylneuraminic acid obtained from glycomacropeptide (G-NANA) of whey through a neuraminidase-mediated reaction and evaluated its antibacterial ability against H. pylori and H. felis. Overnight cultures of the H. pylori were diluted with fresh media and different concentrations (1-150 mg/mL) of crude G-NANA were added directly to the culture tube. Bacterial growth was evaluated by measuring the optical density of the culture medium and the number of viable bacteria was determined by a direct count of the colony forming units (CFU) on agar plates. For the in vivo study, mice were orally infected with 100 uL (5*10(8) cfu/mL) of H. felis four times at a day's interval, accompanied by a daily administration of crude G-NANA or vehicle. A day after the last infection, the mice were daily administered the crude G-NANA (0, 75, and 300 mg/mL) for 10 days and euthanized. Their stomachs were collected and bacterial colonization was determined by quantitative real-time PCR. Crude G NANA inhibited H. pylori's growth and reduced the number of viable bacteria in a dose-dependent manner. Furthermore, crude G-NANA inhibited bacterial colonization in the mice. These results showed that crude G-NANA has antibacterial activity against Helicobacter and demonstrated its therapeutic potential for the prevention of chronic gastritis and gastric carcinogenesis induced by Helicobacter infection in humans. PMID- 27382379 TI - Beneficial effect of diosgenin as a stimulator of NGF on the brain with neuronal damage induced by Abeta-42 accumulation and neurotoxicant injection. AB - To investigate the beneficial effects of diosgenin (DG) on the multiple types of brain damage induced by Abeta-42 peptides and neurotoxicants, alterations in the specific aspects of brain functions were measured in trimethyltin (TMT)-injected transgenic 2576 (TG) mice that had been pretreated with DG for 21 days. Multiple types of damage were successfully induced by Abeta-42 accumulation and TMT injection into the brains of TG mice. However, DG treatment significantly reduced the number of Abeta-stained plaques and dead cells in the granule cells layer of the dentate gyrus. Significant suppression of acetylcholinesterase (AChE) activity and Bax/Bcl-2 expression was also observed in the DG treated TG mice (TG+DG group) when compared with those of the vehicle (VC) treated TG mice (TG+VC group). Additionally, the concentration of nerve growth factor (NGF) was dramatically enhanced in TG+DG group, although it was lower in the TG+VC group than the non-transgenic (nTG) group. Furthermore, the decreased phosphorylation of downstream members in the TrkA high affinity receptor signaling pathway in the TG+VC group was significantly recovered in the TG+DG group. A similar pattern was observed in p75(NTR) expression and JNK phosphorylation in the NGF low affinity receptor signaling pathway. Moreover, superoxide dismutase (SOD) activity was enhanced in the TG+DG group, while the level of malondialdehyde (MDA), a marker of lipid peroxidation, was lower in the TG+DG group than the TG+VC group. These results suggest that DG could exert a wide range of beneficial activities for multiple types of brain damage through stimulation of NGF biosynthesis. PMID- 27382380 TI - Establishment of a mouse model of 70% lethal dose by total-body irradiation. AB - Whereas increasing concerns about radiation exposure to nuclear disasters or side effects of anticancer radiotherapy, relatively little research for radiation damages or remedy has been done. The purpose of this study was to establish level of LD70/30 (a lethal dose for 70% of mice within 30 days) by total-body gamma irradiation (TBI) in a mouse model. For this purpose, at first, 8-week-old male ICR and C57BL/6N mice from A and B companies were received high dose (10, 11, 12 Gy) TBI. After irradiation, the body weight and survival rate were monitored for 30 days consecutively. In next experiment, 5-week-old male ICR and C57BL/6N mice from B company were received same dose irradiation. Results showed that survival rate and body weight change rate in inbred C57BL/6N mice were similar between A and B company. In ICR mice, however, survival rate and body weight change rate were completely different among the companies. Significant difference of survival rate both ICR and C57BL6N mice was not observed in between 5-week-old and 8-week old groups receiving 10 or 12 Gy TBI. Our results indicate that the strain and age of mice, and even purchasing company (especially outbred), should be matched over experimental groups in TBI experiment. Based on our results, 8-week-old male ICR mice from B company subjected to 12 Gy of TBI showed LD70/30 and suitable as a mouse model for further development of new drug using the ideal total-body irradiation model. PMID- 27382381 TI - Detection of Helicobacter felis in a cat with gastric disease in laboratory animal facility. AB - A 3-month-old male cat in the animal facility was presented for investigation of anorexia and occasional vomiting. We collected the specimens from gastroscopic biopsy and stool collection. The gastroscopic biopsy specimens were tested using a rapid urease test, CLO Helicobacter-detection kits. Stool specimens were gathered and evaluated using the commercially available SD Bioline H. pylori Ag kit according to the manufacturer's instructions. Genomic DNAs from gastroscopic biopsy and stool specimens of the cat were extracted and submitted to the consensus PCR to amplify Helicobacter rpoB gene. Then the DNAs from gastroscopic biopsy and stool specimens were conducted a multiplex species-specific PCR to amplify urease B gene for H. heilmannii, H. pylori and H. felis. As the results, the rapid urease test with gastroscopic biopsy was revealed positive reaction. The result of H. pylori Stool Ag assay was one red line, negative for H. pylori. The gastroscopic biopsy and stool specimen were positive reactions by the consensus PCR reaction using the RNA polymerase beta-subunit-coding gene (rpoB) to detect Helicobacter species. By multiplex species-specific PCR with gastroscopic biopsy and stool specimens, no amplification products corresponding to either H. heilmannii or H. pylori were detected, but the specimens tested were positive for H. felis. This case was confirmed as gastroenteric disease induced by H. felis infection. On our knowledge, this is a very rare report about H. felis-induced gastroenteric disease in cat and may provide a valuable data on the study of feline Helicobacter infection. PMID- 27382383 TI - Erratum: Rapid and efficient identification of the mouse leptin receptor mutation (C57BLKS/J-Lepr(db) ) by tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR) analysis. AB - [This corrects the article on p. 70 in vol. 32, PMID: 27051445.]. PMID- 27382382 TI - Differential expression of estrogen receptor alpha and progesterone receptor in the normal and cryptorchid testis of a dog. AB - Descending of the testes is an important process for spermatogenesis and cryptorchidism is one of the most relevant genital defects in dogs. In a previous study, we observed abnormal morphology and proliferation of Sertoli cells in a cryptorchid testis. In the present study, we investigated the expression of estrogen and progesterone receptors in the normal and cryptorchid testis of a dog. Elective orchidectomy was performed on the dog's abdominal right testis (undescended, cryptorchid) and scrotal left testis (descended, normal). In the normal testis, estrogen receptor alpha immunoreactivity was detected in Leydig cells alone, while estrogen receptor alpha immunoreactivity in the cryptorchid testis was significantly prominent in the Sertoli cells as well. In addition, progesterone receptor immunoreactivity in the control testis was detected in the spermatids, but was not detected in the cryptorchid testis. This result suggests that unilateral cryptorchidism causes increases of estrogen receptor alpha expression in Sertoli cells. PMID- 27382384 TI - Withdrawal: Specific nephrotoxicity and cardiotoxicity of BT-CAL(r), Sigma Anti bonding Molecule Calcium Carbonate, in mice. AB - [This retracts the article on p. 7 in vol. 29, PMID: 23573102.]. PMID- 27382386 TI - Breast Cancer Mortality among Asian-American Women in California: Variation according to Ethnicity and Tumor Subtype. AB - PURPOSE: Asian-American women have equal or better breast cancer survival rates than non-Hispanic white women, but many studies use the aggregate term "Asian/Pacific Islander" (API) or consider breast cancer as a single disease. The purpose of this study was to assess the risk of mortality in seven subgroups of Asian-Americans expressing the estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2) tumor marker subtypes and determine whether the risk of mortality for the aggregate API category is reflective of the risk in all Asian ethnicities. METHODS: The study included data for 110,120 Asian and white women with stage 1 to 4 first primary invasive breast cancer from the California Cancer Registry. The Asian ethnicities identified were Pacific Islander, Southeast Asian (SEA), Indian Subcontinent, Chinese, Japanese, Filipino, and Korean. A Cox regression analysis was used to compute the risk of breast cancer-specific mortality in seven Asian ethnicities and the combined API category versus white women within each of the ER/PR/HER2 subtypes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed. RESULTS: For the ER+/PR+/HER2- subtype, the combined API category showed a 17% (HR, 0.83; 95% CI, 0.76-0.91) lower mortality risk. This was true only for SEA (HR, 0.75; 95% CI, 0.61-0.91) and Japanese women (HR, 0.60; 95% CI, 0.45-0.81). In the ER+/PR-/HER2- subtype, SEA (HR, 0.57; 95% CI, 0.38-0.84) and Filipino women (HR, 0.71; 95% CI, 0.51-0.97) had a lower risk of mortality. Japanese (HR, 0.49; 95% CI, 0.25-0.99) and Filipino women (HR, 0.74; 95% CI, 0.58-0.94) had a lower HR for the ER-/PR /HER2+ subtype. For triple-positive, ER+/PR+/HER2+ (HR, 0.84; 95% CI, 0.71-0.98) and triple-negative, ER-/PR-/HER2- (HR, 0.84; 95% CI, 0.74-0.94) subtypes, only the API category showed a lower risk of mortality. CONCLUSION: Breast cancer specific mortality among Asian-American women varies according to their specific Asian ethnicity and breast cancer subtype. PMID- 27382387 TI - Role of STAT3 Phosphorylation in Ethanol-Mediated Proliferation of Breast Cancer Cells. AB - PURPOSE: In this study, we investigated the molecular mechanism involved in ethanol (EtOH)-mediated proliferation of breast cancer cells. METHODS: EtOH concentration was optimized by studying its effect on cell proliferation in MCF-7 and MDA MB-231 cells. We used flow cytometry and immunoblot analysis to evaluate the increased proliferation caused by the optimized concentrations of EtOH. The mechanism of EtOH-mediated proliferation was determined using reactive oxygen species (ROS) release assay, reverse transcription polymerase chain reaction, and immunoblot studies. Gene silencing followed by quantitative real-time polymerase chain reaction studies and inhibitor studies indicated the involvement of signal transducer and activator of transcription 3 (STAT3) in EtOH-mediated breast cancer proliferation. RESULTS: Exposure to EtOH caused an increase in cell proliferation and an accumulation of cells in S-phase in MCF-7 (347 uM EtOH) and MDA MB-231 (173 uM EtOH) cells. Additionally, increased release of ROS and the expression of pro-inflammatory cytokines, such as interleukin 6 and tumor necrosis factor alpha, confirmed that the proliferation was induced by the ROS linked inflammatory response in breast cancer. The proinflammatory response was followed by phosphorylation of STAT3. The importance of STAT3 activation in EtOH mediated proliferation was confirmed through the silencing of STAT3, followed by an investigation on the expression of cyclins and matrix metalloproteinases. Finally, studies using specific inhibitors indicated that the EtOH-mediated effect on STAT3 activation could be regulated by phosphoinositide-3-kinase and Janus kinase 2. CONCLUSION: The study demonstrates the involvement of STAT3 signaling in EtOH-mediated breast cancer proliferation. PMID- 27382385 TI - Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Breast Carcinogenesis. AB - Normal human breast tissue consists of epithelial and nonepithelial cells with different molecular profiles and differentiation grades. This molecular heterogeneity is known to yield abnormal clones that may contribute to the development of breast carcinomas. Stem cells that are found in developing and mature breast tissue are either positive or negative for cytokeratin 19 depending on their subtype. These cells are able to generate carcinogenesis along with mature cells. However, scientific data remains controversial regarding the monoclonal or polyclonal origin of breast carcinomas. The majority of breast carcinomas originate from epithelial cells that normally express BRCA1. The consecutive loss of the BRCA1 gene leads to various abnormalities in epithelial cells. Normal breast epithelial cells also express hypoxia inducible factor (HIF) 1alpha and HIF-2alpha that are associated with a high metastatic rate and a poor prognosis for malignant lesions. The nuclear expression of estrogen receptor (ER) and progesterone receptor (PR) in normal human breast tissue is maintained in malignant tissue as well. Several controversies regarding the ability of ER and PR status to predict breast cancer outcome remain. Both ER and PR act as modulators of cell activity in normal human breast tissue. Ki-67 positivity is strongly correlated with tumor grade although its specific role in applied therapy requires further studies. Human epidermal growth factor receptor 2 (HER2) oncoprotein is less expressed in normal human breast specimens but is highly expressed in certain malignant lesions of the breast. Unlike HER2, epidermal growth factor receptor expression is similar in both normal and malignant tissues. Molecular heterogeneity is not only found in breast carcinomas but also in normal breast tissue. Therefore, the molecular mapping of normal human breast tissue might represent a key research area to fully elucidate the mechanisms of breast carcinogenesis. PMID- 27382388 TI - Aberrant Promoter Methylation at CpG Cytosines Induce the Upregulation of the E2F5 Gene in Breast Cancer. AB - PURPOSE: The promoter methylation status of cell cycle regulatory genes plays a crucial role in the regulation of the eukaryotic cell cycle. CpG cytosines are actively subjected to methylation during tumorigenesis, resulting in gain/loss of function. E2F5 gene has growth repressive activities; various studies suggest its involvement in tumorigenesis. This study aims to investigate the epigenetic regulation of E2F5 in breast cancer to better understand tumor biology. METHODS: The promoter methylation status of 50 breast tumor tissues and adjacent normal control tissues was analyzed. mRNA expression was determined using SYBR(r) green quantitative polymerase chain reaction (PCR), and methylation-specific PCR was performed for bisulfite-modified genomic DNA using E2F5-specific primers to assess promoter methylation. Data was statistically analyzed. RESULTS: Significant (p<0.001) upregulation was observed in E2F5 expression among tumor tissues, relative to the control group. These samples were hypo-methylated at the E2F5 promoter region in the tumor tissues, compared to the control. Change in the methylation status (Deltameth) was significantly lower (p=0.022) in the tumor samples, indicating possible involvement in tumorigenesis. Patients at the postmenopausal stage showed higher methylation (75%) than those at the premenopausal stage (23.1%). Interestingly, methylation levels gradually increased from the early to the advanced stages of the disease (p<0.001), which suggests a putative role of E2F5 methylation in disease progression that can significantly modulate tumor biology at more advanced stage and at postmenopausal age (Pearson's r=0.99 and 0.86, respectively). Among tissues with different histological status, methylation frequency was higher in invasive lobular carcinoma (80.0%), followed by invasive ductal carcinoma (46.7%) and ductal carcinoma in situ (20.0%). CONCLUSION: Methylation is an important epigenetic factor that might be involved in the upregulation of E2F5 gene in tumor tissues, which can be used as a prognostic marker for breast cancer. PMID- 27382389 TI - Hornerin Is Involved in Breast Cancer Progression. AB - PURPOSE: The S100 gene family, which comprises over 20 members, including S100A1, S100A2, S100A8, S100A9, profilaggrin, and hornerin encodes low molecular weight calcium-binding proteins with physiological and pathological roles in keratinization. Recent studies have suggested a link between S100 proteins and human cancer progression. The purpose of the present study was to determine the expression levels of hornerin, S100A8, and S100A9 and evaluate their roles in the progression of invasive ductal carcinoma (IDC). METHODS: Seventy cases of ductal carcinoma in situ (DCIS), IDC, and metastatic carcinoma in lymph nodes (MCN) were included. Tissue microarrays were constructed from lesions of DCIS, IDC, and MCN from the same patients. Expression of hornerin, S100A8, and S100A9 was analyzed using immunohistochemistry. RESULTS: The expression of hornerin was associated with the estrogen receptor-negative (p=0.003) and the human epidermal growth factor receptor 2-positive (p=0.002) groups. The expression of S100A8 was associated with a higher pT stage (p=0.017). A significant (p<0.001) correlation between the expression of S100A9 and S100A8 was also found. The mean percentages of hornerin-positive tumor cells in DCIS, IDC, and MCN were 1.0%+/-3.3% (mean+/ standard deviation), 12.0%+/-24.0%, and 75.3%+/- 27.6%, respectively. The expression of hornerin significantly (p<0.001) increased with the progression of carcinoma. The mean levels of S100A8 and S100A9 in DCIS, IDC, and MCN were not significantly (p>0.050) different. The expression of hornerin increased in a stepwise manner (DCIS3.0) (p=0.020), high nodal ratio (number of metastatic lymph nodes divided by number of removed nodes) (>0.65) (p=0.062), and molecular phenotype (p=0.012) were significantly associated with tumor recurrence. Tumor biological subtype was the most significant predictor of recurrence. The 5-year DFS rates in patients with hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative, HR+HER2+, HR-HER2+, and triple negative subtypes were 82%, 63%, 58%, and 37%, respectively. CONCLUSION: Clinical outcomes of patients with extensive nodal metastasis were heterogeneous in terms of prognosis. Tumor biological subtype was the most important prognostic factor for pN3 disease. The prognosis of patients with HR+HER2- subtype in pN3 breast cancer was similar to that of patients with stage II breast cancer. PMID- 27382393 TI - Lymph Node Ratio as a Risk Factor for Locoregional Recurrence in Breast Cancer Patients with 10 or More Axillary Nodes. AB - PURPOSE: We analyzed the association of lymph node ratio (LNR) wth locoregional control (LRC) in breast cancer patients with >=10 involved axillary lymph nodes who underwent multimodality treatment. METHODS: We retrospectively analyzed 234 breast cancer patients with >=10 involved axillary lymph nodes between 2000 and 2011. All patients received adjuvant chemotherapy and radiotherapy (RT) after radical surgery. The cutoff value of LNR was obtained using receiver operating characteristic curve analysis. The majority of patients (87.2%) received chemotherapeutic regimen including taxane. RT consisted of tangential fields to the chest wall or intact breast, delivered at a median dose of 50 Gy, and a single anterior port to the supraclavicular lymph node area, delivered at a median dose of 50 Gy. For patients who underwent breast-conserving surgery, an electron boost with a total dose of 9 to 15 Gy was delivered to the tumor bed. RESULTS: Within a median follow-up period of 73.5 months (range, 11-183 months), locoregional recurrence (LRR) occurred in 30 patients (12.8%) and the 5-year LRC rate was 88.8%. After multivariate analysis, LNR >=0.7 was the only independent factor significantly associated with LRC (hazard ratio, 2.06; 95% confidence interval, 0.99-4.29; p=0.05). CONCLUSION: An aggressive multimodal treatment approach showed favorable locoregional outcome in patients with >=10 involved axillary lymph nodes. However, patients with a high LNR >=0.7 still had an increased risk for LRR, even in the setting of current local treatments. PMID- 27382394 TI - Predictive Value of Molecular Subtyping for Locoregional Recurrence in Early Stage Breast Cancer with N1 without Postmastectomy Radiotherapy. AB - PURPOSE: This study was designed to investigate the relationship between molecular subtype and locoregional recurrence (LRR) in patients with early-stage breast cancer with 1-3 positive axillary lymph nodes (ALNs) and improve the individualized indications for postmastectomy radiotherapy (PMRT). METHODS: The records of 701 patients with pT1-2N1M0 breast cancer who did not undergo PMRT were retrospectively analyzed. Tumors were subclassified as follows: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and basal like subtypes. Multivariate Cox analysis was used to determine the risk of LRR associated with the different subtypes and to adjust for clinicopathologic factors. RESULTS: Luminal A, luminal B, HER2-enriched, and basal-like subtypes accounted for 51.2%, 28.0%, 8.1%, and 12.7% of cases, respectively. The median follow-up duration was 67 months (range, 9-156 months). Univariate analysis revealed that, compared with the luminal A subtype, the HER2-enriched and basal like subtypes were associated with significantly higher 5-year LRR rates (5.6% vs. 21.6% and vs.15.7% respectively; p=0.002 each), lower 5-year LRR-free survival (LRFS) rates (90.6% vs. 73.8% and 78.5%, respectively; p=0.001 each), and poorer 5-year breast cancer-specific survival (BCSS) rates (93.7% vs. 82.2% [p=0.002] and 84.9% [p=0.001], respectively). Multivariate analysis revealed that the HER2-enriched and basal-like subtypes, age <=35 years, a medial tumor, and pT2 stage were poor prognostic factors for LRR and LRFS; furthermore, 2 to 3 positive ALNs represented an independent prognostic factor affecting LRR. The 10 year LRR rates of patients with 0, 1, 2, 3, and 4 risk factors were 1.0%, 6.9%, 14.3%, 30.4%, and 54.3%, respectively (p<0.001); the 10-year BCSS rates were 86.6%, 88.5%, 84.4%, 79.7%, and 38.8%, respectively (p<0.001). CONCLUSION: Molecular subtyping allows for individualized evaluation of LRR risk in patients with pT1-2N1M0 breast cancer. PMRT should be recommended for patients with >=3 LRR risk factors. PMID- 27382395 TI - Predictors of Recurrent Ductal Carcinoma In Situ after Breast-Conserving Surgery. AB - PURPOSE: Local recurrence is a major concern in patients who have undergone surgery for ductal carcinoma in situ (DCIS). The present study assessed whether the expression levels of hormone receptors, human epidermal growth factor receptor 2 (HER2), and Ki-67, as well as resection margin status, tumor grade, age at diagnosis, and adjuvant hormonal therapy and radiotherapy (RT) are associated with recurrence in women with DCIS. METHODS: In total, 111 patients with DCIS were included in the present study. The invasive and noninvasive recurrence events were recorded. The clinicopathological features; resection margins; administration of hormonal therapy and RT; expression statuses of estrogen receptor (ER), progesterone receptor (PR), and HER2; Ki-67 expression; and molecular subtypes were evaluated. Logistic regression analysis was performed to examine the risk factors for recurrence. RESULTS: Recurrence was noted in 27 of 111 cases (24.3%). Involvement of resection margins, low tumor grade, high Ki 67 expression, and RT were independently associated with an increase in the recurrence rate (p<0.05, Pearson chi-square test). The recurrence rate was not significantly associated with patient age; ER, PR, and HER2 statuses; molecular subtype; and hormonal therapy. CONCLUSION: The results of the present study suggested that the involvement of resection margins, low tumor grade, high Ki-67 index, and the absence of adjuvant RT were independently associated with increased recurrence in patients with DCIS. Future studies should be conducted in a larger cohort of patients to further improve the identification of patients at high-risk for DCIS recurrence. PMID- 27382396 TI - Breast Magnetic Resonance Imaging for Assessment of Internal Mammary Lymph Node Status in Breast Cancer. AB - PURPOSE: The purpose of this study was to assess magnetic resonance imaging (MRI) features of malignant internal mammary lymph nodes (IMLNs) and benign IMLNs in breast cancer patients. METHODS: From 2009 to 2014, the records of 85 patients with IMLNs were archived using MRI report data; 26 patients with small size (long axis diameter <5 mm) nodes were subsequently excluded. The current study evaluated internal mammary lymph nodes in 59 patients who underwent breast MRI for breast cancer staging and for posttherapy follow-up. All MRI findings were retrospectively evaluated. Malignancy was determined based on pathologic examination and positron emission tomography computed tomography findings. Independent t-tests, Mann-Whitney U tests, chi-square tests, and receiver operating characteristics (ROC) curve analysis were used. RESULTS: Among MRI features, there were statistically significant differences between benign and malignant IMLN groups, in short axis length (3.6+/-1.3 vs. 8.2+/-2.9 mm, respectively), long axis length (8.1+/-2.4 vs. 14.5+/-4.8 mm, respectively), short/long axis ratio (0.45+/-0.10 vs. 0.59+/-0.17, respectively), absent fatty hilum (mean, 0% vs. 95%, respectively), and restricted diffusion (15.8% vs. 85.0%, respectively) (p<0.050). Multiplicity and location of intercostal spaces was not different between the two groups. Short axis length was the most discriminative variable for predicting metastatic nodes (area under the ROC curve, 0.951; threshold, 4 mm; sensitivity, 92.5%; specificity, 84.2%). CONCLUSION: Conventional MRI and diffusion-weighted MRI are helpful to detect metastasis of internal mammary lymph nodes in breast cancer. PMID- 27382397 TI - Features of Pure Lobular Carcinoma In Situ on Magnetic Resonance Imaging Associated with Immediate Re-Excision after Lumpectomy. AB - PURPOSE: To evaluate imaging features of pure lobular carcinoma in situ (LCIS) on magnetic resonance imaging (MRI) in patients who underwent immediate re-excision after lumpectomy. METHODS: Twenty-six patients (46.1+/-6.7 years) with 28 pure LCIS lesions, who underwent preoperative MRI and received curative surgery at our institution between 2005 and 2013, were included in this study. Clinicopathologic features associated with immediate re-excision were reviewed and analyzed using Fisher exact test or the Wilcoxon signed rank test. RESULTS: Of the 28 lesions, 21.4% (6/28, six patients) were subjected to immediate re-excision due to resection margin involvement by LCIS. Nonmass lesions and moderate-to-marked background parenchymal enhancement on MRI were more frequently found in the re excision group than in the single operation group (100% [6/6] vs. 40.9% [9/22], p=0.018; 83.3% [5/6] vs. 31.8% [7/22], p=0.057, respectively). The median lesion size discrepancy observed between magnetic resonance images and histopathology was greater in the re-excision group than in the single operation group (-0.82 vs. 0.13, p=0.018). There were no differences in the mammographic or histopathologic findings between the two groups. CONCLUSION: Nonmass LCIS lesions or moderate-to-marked background parenchymal enhancements on MRI can result in an underestimation of the extent of the lesions and are associated with subsequent re-excision due to resection margin involvement. PMID- 27382398 TI - Mu-Opioid Receptor Polymorphisms and Breast Cancer in a Korean Female Adult Population: A Retrospective Study. AB - Distribution of A118G single nucleotide polymorphism (SNP) in the mu-opioid receptor 1 gene (OPRM1) differs with ethnicity. We assessed the distribution of this SNP in Korean women with breast cancer and compared it with that in women of other ethnicities with breast cancer. Distribution of SNP genotypes was as follows: 49.8% for AG genotype, 40.6% for AA genotype, and 9.6% for GG genotype. Logistic regression analysis showed a negative association between the presence of the G allele at position 118 of OPRM1 and breast cancer in the studied population (odds ratios [OR], 0.635; p=0.002). However, the AG and GG genotypes were not associated with breast cancer in the studied population (OR, 0.719; p=0.130). The proportions of the AG and GG genotypes of the OPRM1 SNP were higher in Korean women with breast cancer than in those of other ethnicities. PMID- 27382399 TI - An Innovative Ultrasound Technique for Evaluation of Tumor Vascularity in Breast Cancers: Superb Micro-Vascular Imaging. AB - Tumor vascularity is an important indicator for differential diagnosis, tumor growth, and prognosis. Superb micro-vascular imaging (SMI) is an innovative ultrasound technique for vascular examination that uses a multidimensional filter to eliminate clutter and preserve extremely low-velocity flows. Theoretically, SMI could depict more vessels and more detailed vascular morphology, due to the increased sensitivity of slow blood flow. Here, we report the early experience of using SMI in 21 breast cancer patients. We evaluated tumor vascular features in breast cancer and compared SMI and conventional color or power Doppler imaging. SMI was superior to color or power Doppler imaging in detecting tumor vessels, the details of vessel morphology, and both peripheral and central vascular distribution. In conclusion, SMI is a promising ultrasound technique for evaluating microvascular information of breast cancers. PMID- 27382400 TI - Eribulin Mesylate Combined with Local Treatment for Brain Metastasis from Breast Cancer: Two Case Reports. AB - The prognosis associated with brain metastasis arising from breast cancer is very poor. Eribulin is a microtubule dynamic inhibitor synthesized from halichondrin B, a natural marine product. In a phase III study (EMBRACE), eribulin improved overall survival in patients with heavily pretreated metastatic breast cancers. However, these studies included few patients with brain metastases. Metastatic brain tumors (MBT) were detected during first-line palliative chemotherapy in a 43-year-old woman with breast cancer metastasis to the lung and mediastinal nodes; the genetic subtype was luminal B-like human epidermal growth factor receptor 2 (HER2)-negative. Whole brain radiotherapy (WBRT) followed by eribulin treatment continuously decreased the size, and induced regression, of the MBT with systemic disease stability for 12 months. Another 48-year-old woman with metastatic breast cancer (HER2+ subtype) presented with MBT. Following surgical resection of the tumor, eribulin with concurrent WBRT showed regression of the MBT without systemic progression for 18 months. PMID- 27382401 TI - Experience with Bilateral Risk-Reducing Mastectomy for an Unaffected BRCA Mutation Carrier. AB - Women with BRCA1/2 mutations have a high risk of breast cancer and may opt for risk-reducing mastectomy (RRM). We report a 38-year-old Japanese woman who was diagnosed as a BRCA2 mutation carrier. She underwent prophylactic bilateral skin sparing mastectomy (SSM) with excision of the nipple and preservation of the areola skin. It is unclear whether a bilateral RRM leads to better survival compared with intensive surveillance. The oncological risk associated with the presence of remnant breast glandular tissue after SSM or nipple-sparing mastectomy has been obscure. We report the first case of RRM for a Japanese BRCA mutation carrier and provide a literature review on risk management for BRCA mutation carriers with a focus on the concepts and procedures of RRM. PMID- 27382402 TI - Evaluation of Anti-Inflammatory Potential of the New Ganghwaljetongyeum on Adjuvant-Induced Inflammatory Arthritis in Rats. AB - Ganghwaljetongyeum (GHJTY) has been used as a standard treatment for arthritis for approximately 15 years at the Korean Medicine Hospital of Dongshin University. GHJTY is composed of 18 medicinal herbs, of which five primary herbs were selected and named new Ganghwaljetongyeum (N-GHJTY). The purpose of the present study was to observe the effect of N-GHJTY on arthritis and to determine its mechanism of action. After confirming arthritis induction using complete Freund's adjuvant (CFA) in rats, N-GHJTY (62.5, 125, and 250 mg/kg/day) was administered once a day for 10 days. In order to determine pathological changes, edema of the paws and weight were measured before and for 10 days after N-GHJTY administration. Cytokine (TNF-alpha, IL-1beta, and IL-6) levels and histopathological lesions in the knee joint were also examined. Edema in the paw and knee joint of N-GHJTY-treated rats was significantly decreased at 6, 8, and 10 days after administration, compared to that in the CFA-control group, while weight consistently increased. Rats in N-GHJTY-treated groups also recovered from the CFA-induced pathological changes and showed a significant decline in cytokine levels. Taken together, our results showed that N-GHJTY administration was effective in inhibiting CFA-induced arthritis via anti-inflammatory effects while promoting cartilage recovery by controlling cytokine levels. PMID- 27382403 TI - Comparison of the Effect of Velvet Antler from Different Sections on Longitudinal Bone Growth of Adolescent Rats. AB - The aim of this study was to compare the effectiveness of velvet antler (VA) from different sections for promoting longitudinal bone growth in growing rats. VA was divided into upper (VAU), middle (VAM), and basal sections (VAB). An in vivo study was performed to examine the effect on longitudinal bone growth in adolescent rats. In addition, in vitro osteogenic activities were examined using osteoblastic MG-63 cells. VA promoted longitudinal bone growth and height of the growth plate in adolescent rats. Bone morphogenetic protein-2 (BMP-2) in growth plate of VA group was highly expressed compared with control. The anabolic effect of VA on bone was further supported by in vitro study. VA enhanced the proliferation, differentiation, and mineralization of MG-63 cells. The mRNA expressions of osteogenic genes such as collagen, alkaline phosphatase, and osteocalcin were increased by VA treatment. These effects of in vivo and in vitro study were decreased from upper to basal sections of VA. In conclusion, VA treatment promotes longitudinal bone growth in growing rats through enhanced BMP 2 expression, osteogenic activities, and bone matrix gene expressions. In addition, present study provides evidence for the regional differences in the effectiveness of velvet antler for longitudinal bone growth. PMID- 27382404 TI - The Effect of Seoritae Extract in Men with Mild to Moderate Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia. AB - We evaluated the effects of Seoritae extract (SE) on mild to moderate lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). Seventy-six subjects with mild to moderate LUTS suggestive of BPH were prospectively recruited from the urology outpatient clinic and assigned to either SE (4200 mg or 6 tablets 3 times a day) or matching placebo. The primary outcome variable, the International Prostatic Symptom Score (IPSS), was evaluated at baseline and at 4 and 12 weeks. Postvoid residual volume (PVR), maximum urine flow rate (Q max), and prostate-specific antigen (PSA) levels were evaluated. IPSSs decreased significantly from baseline to 12 weeks within the SE group. Significant improvements in IPSS voiding scores at 4 and 12 weeks were also observed in the SE group compared to the placebo group. IPSS storage and quality of life scores were also significantly decreased at 12 weeks in the SE group. There was no change in Q max or PVR in both groups after 12 weeks. Administration of SE for 12 weeks led to significant improvements in LUTS, and it can be concerned as a reasonable and safe alternative for men with mild to moderate LUTS. PMID- 27382405 TI - A Meta-Analysis of Arsenic Trioxide Combined with Transcatheter Arterial Chemoembolization for Treatment of Primary Hepatic Carcinoma. AB - Primary hepatic carcinoma (PHC) is one of the most common malignant tumours in the world. More and more research has shown that As2O3 combined with TACE has a good curative effect in treating PHC. The objectives of this study were to evaluate the therapeutic efficacy and safety of As2O3 combined with TACE in treating PHC. The CNKI, VIP, Wanfang, PubMed, and Cochrane databases were searched from their inception until December 2015. Randomized controlled trials (RCTs) comparing As2O3 combined with TACE versus TACE alone in treating PHC were identified. Stata SE 12.0 was used for data analysis. 17 RCTs with 1055 patients were included. Meta-analysis showed that, compared with TACE alone, As2O3 combined with TACE showed significant effects in improving the clinical efficacy rate (P < 0.01), decreasing the value of alpha-fetoprotein (P < 0.01), increasing the one-year survival rate (P < 0.01), and improving the quality of life of PHC patients (P < 0.01). Fifteen studies had mentioned adverse events, but no serious adverse effects were reported in any of the included trials. In conclusion, As2O3 combined with TACE therapy appears to be potentially effective in treating PHC and is generally safe. However, further studies with rigorous designs trials and multiregional cooperation trials are needed. PMID- 27382406 TI - Miniscalpel-Needle Treatment Is Effective for Work-Related Neck and Shoulder Musculoskeletal Disorders. AB - Background. Work-related musculoskeletal disorders (MSDs) are a group of painful disorders of muscles, tendons, and nerves, such as neck and shoulder MSD. This study was designed to use miniscalpel-needle (MSN) technique as an intervention for work-related MSDs. Methods. Thirty-one patients with work-related MSDs and 28 healthy subjects were enrolled as controls in this study. The MSD symptoms of each patient were assessed by visual analog scale (VAS) and neck disability index (NDI). Blood samples were collected from control subjects and MSD patients before and after treatment. Serum levels of C-reactive protein (CRP) and tumor necrosis factor (TNF) were measured using ELISA. Results. Prior to MSN treatment, serum levels of CRP and TNF were significantly higher in the MSD patients than the healthy controls. Serum CRP levels correlated with VAS and NDI scores, and serum TNF levels correlated with NDI scores. Compared to pretreatment, VAS and NDI scores were significantly lower in MSD patients after MSN treatment, while serum CRP and TNF levels were significantly lower compared with the healthy control levels. Conclusions. Our results indicate that MSN may be an effective intervention for work-related MSDs and be associated with lower serum levels of inflammatory biomarkers. PMID- 27382407 TI - Pleural fluid metastases of myoepithelial carcinoma: A case report and review of the literature. AB - Myoepithelial carcinoma (MECA) is one of the rarest salivary gland neoplasms, which may either arise de novo or develop within a preexisting pleomorphic adenoma or benign myoepithelioma. The tumor occurs mainly in the parotid gland followed by minor salivary glands and other body sites. As a result of their morphologic heterogeneity, they can be confused easily with many tumors. Awareness of their unique cytoarchitectural patterns and immunohistochemical profile is crucial for accurate identification. Herein, we report a rare case of a 51-year-old female patient with MECA of the maxillary sinus that metastasized to the pleural fluid. To the best of our knowledge, this is the first case of pleural fluid involvement by MECA reported in the literature. PMID- 27382408 TI - Unsatisfactory rate in liquid-based cervical samples as compared to conventional smears: A study from tertiary care hospital. AB - BACKGROUND: Developed countries adopted liquid-based cytology (LBC) cervical cytology, partly because of its lower proportions of unsatisfactory (U/S)/inadequate samples. This study was carried out to evaluate effect on the rate of U/S samples after introduction of LBC in our laboratory. MATERIALS AND METHODS: An audit of U/S cervical samples was performed, which included split samples (n = 1000), only conventional Pap smear (CPS) smears (n = 1000), and only LBC samples (n = 1000). The smears were reviewed by two observers independently, and adequacy for the samples was assessed as per The Bethesda System 2001. The reasons for U/S rate in split samples were categorized into various cytologic and/or technical reasons. RESULTS: U/S rate was far less in only LBC samples (1.2%) as compared to only CPS (10.5%) cases. Cases in the satisfactory but limited category were also less in only LBC (0.4%) as compared to only CPS (3.2%) samples. The main reasons for U/S smears in split samples were low cell count (37.2% in CPS; 58.8% in LBC). The second main reason was low cellularity with excess blood and only excess blood in CPS samples. CONCLUSION: There was a significant reduction of U/S rate in LBC samples as compared to CPS samples, and the difference was statistically significant. The main cause of U/S samples in LBC was low cellularity indicating a technical fault in sample collection. The main cause of U/S rate in CPS was low cellularity followed by low cellularity with excess blood. Adequate training of sample takers and cytologists for the precise cell count to determine adequacy in smears can be of great help in reducing U/S rate. PMID- 27382409 TI - Recombinant human growth hormone and insulin-like growth factor-1 do not affect mitochondrial derived highly reactive oxygen species production in peripheral blood mononuclear cells under conditions of substrate saturation in-vitro. AB - BACKGROUND: The purpose of this study was to investigate the mitochondrial effects exerted by physiological and supra-physiological concentrations of recombinant human growth hormone (rhGH) and recombinant insulin-like growth factor-1 (rIGF-1) under conditions of substrate saturation in peripheral blood mononuclear cells (PBMCs). METHODS: PBMCs from healthy male subjects were treated with either rhGH, at concentrations of 0.5, 5 and 50 MUg/L, or rIGF-1 at concentrations of 100, 300 and 500 MUg/L for 4 h. Mitochondrial membrane potential (Deltapsim) and mitochondrial levels of highly reactive oxygen species (hROS) were subsequently analysed. This analysis was performed by flow cytometry in digitonin permeabilized cells, following treatment with saturating concentrations of various respiratory substrate combinations and the use of specific electron transport chain (ETC.) complex inhibitors, enabling control over both the sites of electron entry into the ETC. at complexes I and II and the entry of electrons from reduced carriers involved in beta-oxidation at the level of ubiquinol. RESULTS: Neither rhGH nor rIGF-1 exerted any significant effect on Deltapsim or the rate of hROS production in either lymphocyte or monocyte sub populations under any of the respiratory conditions analysed. CONCLUSION: That neither hormone was capable of attenuating levels of oxidative stress mediated via either complex I linked respiration or lipid-derived respiration could have serious health implications for the use of rhGH in healthy individuals, which is frequently associated with significant increases in the bioavailability of free fatty acids (FFA). Such elevated supplies of lipid-derived substrates to the mitochondria could lead to oxidative damage which would negatively impact mitochondrial function. PMID- 27382410 TI - Relapses of primary cutaneous anaplastic large-cell lymphoma in a female immunocompetent patient with persistent chlamydophila pneumoniae and human herpesvirus 8 infection. AB - BACKGROUND: We have previously reported the case of an immunocompetent female patient with a primary cutaneous CD30+ anaplastic large-cell lymphoma (PCALCL) located on her upper right eyelid characterized by the presence of a concurrent active infection by C. pneumoniae and Human herpesvirus 8 (HHV8). This finding suggested for the first time a possible association of C. pneumoniae and/or HHV8 infection, or both together, with PCALCL pathogenesis in non-immunocompromised and HIV-negative subjects. The subsequent course of the same patient's medical history is herein reported. FINDINGS: During the 4 years following the surgical excision of the first PCALCL, the patient developed five further skin lesions located at different anatomical sites, all histologically proven as PCALCLs. The patient underwent several cycles of doxycycline as prophylaxis against Chlamydia. Skin presence of Chlamydia spp and HHV8 was investigated in all recurrences as well as in routine control blood samples. Amplification fragments corresponding to Chlamydia were found in all skin tissues analysed except one (4/5; 80 %), whereas it was not detected in any of the peripheral blood mononuclear cell samples. Conversely, HHV8 was detected in 2/5 (40 %) of the skin biopsies, including the sample negative for Chlamydia, but in all the blood samples analysed. CONCLUSIONS: These findings further support the hypothesis of a potential role of C. pneumoniae and HHV8 infection in the development and course of the described cutaneous lymphoma. A reciprocally promoting interaction between the two pathogens may be supposed to be relevant for PCALC occurrence and relapse. PMID- 27382411 TI - Synthesis and fungicidal activity of pyrazole derivatives containing 1,2,3,4 tetrahydroquinoline. AB - BACKGROUND: Take-all of wheat, caused by the soil-borne fungus Gaeumannomyces graminis var. tritici, is one of the most important and widespread root diseases. Given that take-all is still hard to control, it is necessary to develop new effective agrochemicals. Pyrazole derivatives have been often reported for their favorable bioactivities. In order to discover compounds with high fungicidal activity and simple structures, 1,2,3,4-tetrahydroquinoline, a biologically active group of natural products, was introduced to pyrazole structure. A series of pyrazole derivatives containing 1,2,3,4-tetrahydroquinoline were synthesized, and their fungicidal activities were evaluated. RESULTS: The bioassay results demonstrated that the title compounds displayed obvious fungicidal activities at a concentration of 50 MUg/mL, especially against V. mali, S. sclerotiorum and G. graminis var. tritici. The inhibition rates of compounds 10d, 10e, 10h, 10i and 10j against G. graminis var. tritici were all above 90 %. Even at a lower concentration of 16.7 MUg/mL, compounds 10d and 10e exhibited satisfied activities of 100 % and 94.0 %, respectively. It is comparable to that of the positive control pyraclostrobin with 100 % inhibition rate. CONCLUSION: A series of pyrazole derivatives containing 1,2,3,4-tetrahydroquinoline were synthesized and their structures were confirmed by (1)H NMR, (13)C NMR, IR spectrum and HRMS or elemental analysis. The crystal structure of compound 10g was confirmed by X ray diffraction. Bioassay results indicated that all title compounds exhibited obvious fungicidal activities. In particular, compounds 10d and 10e showed comparable activities against G. graminis var. tritici with the commercial fungicide pyraclostrobin at the concentration of 16.7 MUg/mL.Graphical abstractA series of pyrazole derivatives containing 1,2,3,4-tetrahydroquinoline were designed and synthesized. Bioassay results indicated that all these compounds exhibited obvious fungicidal activities. PMID- 27382412 TI - Inter-rater reliability and acceptance of the structured diagnostic interview for regulatory problems in infancy. AB - BACKGROUND: Regulatory problems such as excessive crying, sleeping-and feeding difficulties in infancy are some of the earliest precursors of later mental health difficulties emerging throughout the lifespan. In the present study, the inter-rater reliability and acceptance of a structured computer-assisted diagnostic interview for regulatory problems (Baby-DIPS) was investigated. METHODS: Using a community sample, 132 mothers of infants aged between 3 and 18 months (mean age = 10 months) were interviewed with the Baby-DIPS regarding current and former (combined = lifetime) regulatory problems. Severity of the symptoms was also rated. The interviews were conducted face-to-face at a psychology department at the university (51.5 %), the mother's home (23.5 %), or via telephone (25.0 %). Inter-rater reliability was assessed with Cohen's kappa (k). A sample of 48 mothers and their interviewers filled in acceptance questionnaires after the interview. RESULTS: Good to excellent inter-rater reliability on the levels of current and lifetime regulatory problems (k = 0.77 0.98) were found. High inter-rater agreement was also found for ratings of severity (ICC = 0.86-0.97). Participants and interviewers' overall acceptance ratings of the computer-assisted interview were favourable. Acceptance scores did not differ between interviews that revealed one or more clinically relevant regulatory problem(s) compared to those that revealed no regulatory problems. CONCLUSIONS: The Baby-DIPS was found to be a reliable instrument for the assessment of current and lifetime problems in crying and sleeping behaviours. The computer-assisted version of the Baby-DIPS was well accepted by interviewers and mothers. The Baby-DIPS appears to be well-suited for research and clinical use to identify infant regulatory problems. PMID- 27382413 TI - Transcriptome profiling of Camelina sativa to identify genes involved in triacylglycerol biosynthesis and accumulation in the developing seeds. AB - BACKGROUND: Camelina sativa is an emerging dedicated oilseed crop designed for biofuel and biodiesel applications as well as a source for edible and general purpose oils. Such valuable oilseed crop is subjected to plant breeding programs and is suggested for large-scale production of better seed and oil quality. To accomplish this objective and to further enhance its oil content, a better understanding of lipid metabolism at the molecular level in this plant is critical. Here, we applied tissue transcriptomics and lipid composition analysis to identify and profile the genes and gene networks associated with triacylglycerol (TAG) biosynthesis, and to investigate how those genes are interacting to determine the quantity and quality of Camelina oil during seed development. RESULTS: Our Camelina transcriptome data analysis revealed an approximate of 57,854 and 57,973 genes actively expressing in developing seeds (RPKM >= 0.1) at 10-15 (Cs-14) and 16-21 (Cs-21) days after flowering (DAF), respectively. Of these, 7932 genes showed temporal and differential gene expression during the seed development (log2 fold change >=1.5 or <=-1.5; P <= 0.05). The differentially expressed genes (DEGs) were annotated and were found to be involved in distinct functional categories and metabolic pathways. Furthermore, performing quantitative real-time PCR for selected candidate genes associated with TAG biosynthesis validated RNA-seq data. Our results showed strong positive correlations between the expression abundance measured using both qPCR and RNA-Seq technologies. Furthermore, the analysis of fatty-acid content and composition revealed major changes throughout seed development, with the amount of oil accumulate rapidly at early mid seed development stages (from 16-28 DAF onwards), while no important changes were observed in the fatty-acid profile between seeds at 28 DAF and mature seeds. CONCLUSIONS: This study is highly useful for understanding the regulation of TAG biosynthesis and identifying the rate-limiting steps in TAG pathways at seed development stages, providing a precise selection of candidate genes for developing Camelina varieties with improved seed and oil yields. PMID- 27382414 TI - Engineering yeast with bifunctional minicellulosome and cellodextrin pathway for co-utilization of cellulose-mixed sugars. AB - BACKGROUND: Consolidated bioprocessing (CBP), integrating cellulase production, cellulose saccharification, and fermentation into one step has been widely considered as the ultimate low-cost configuration for producing second-generation fuel ethanol. However, the requirement of a microbial strain able to hydrolyze cellulosic biomass and convert the resulting sugars into high-titer ethanol limits CBP application. RESULTS: In this work, cellulolytic yeasts were developed by engineering Saccharomyces cerevisiae with a heterologous cellodextrin utilization pathway and bifunctional minicellulosomes. The cell-displayed minicellulosome was two-scaffoldin derived, and contained an endoglucanase and an exoglucanase, while the intracellular cellodextrin pathway consisted of a cellodextrin transporter and a beta-glucosidase, which mimicked the unique cellulose-utilization system in Clostridium thermocellum and allowed S. cerevisiae to degrade and use cellulose without glucose inhibition/repression on cellulases and mixed-sugar uptake. Consequently, only a small inoculation of the non-induced yeast cells was required to efficiently co-convert both cellulose and galactose to ethanol in a single-step co-fermentation process, achieving a high specific productivity of ~62.61 mg cellulosic ethanol/g cell.h from carboxymethyl cellulose and ~56.37 mg cellulosic ethanol/g cell.h from phosphoric acid-swollen cellulose. CONCLUSIONS: Our work provides a versatile engineering strategy for co conversion of cellulose-mixed sugars to ethanol by S. cerevisiae, and the achievements in this work may further promote cellulosic biofuel production. PMID- 27382415 TI - Discovery of new cellulases from the metagenome by a metagenomics-guided strategy. AB - BACKGROUND: Energy shortage has become a global problem. Production of biofuels from renewable biomass resources is an inevitable trend of sustainable development. Cellulose is the most abundant and renewable resource in nature. Lack of new cellulases with unique properties has become the bottleneck of the efficient utilization of cellulose. Environmental metagenomes are regarded as huge reservoirs for a variety of cellulases. However, new cellulases cannot be obtained easily by functional screening of metagenomic libraries. RESULTS: In this work, a metagenomics-guided strategy for obtaining new cellulases from the metagenome was proposed. Metagenomic sequences of DNA extracted from the anaerobic beer lees converting consortium enriched at thermophilic conditions were assembled, and 23 glycoside hydrolase (GH) sequences affiliated with the GH family 5 were identified. Among the 23 GH sequences, three target sequences (designated as cel7482, cel3623 and cel36) showing low identity with those known GHs were chosen as the putative cellulase genes to be functionally expressed in Escherichia coli after PCR cloning. The three cellulases were classified into endo-beta-1,4-glucanases by product pattern analysis. The recombinant cellulases were more active at pH 5.5 and within a temperature range of 60-70 degrees C. Computer-assisted 3D structure modeling indicated that the active residues in the active site of the recombinant cellulases were more similar to each other compared with non-active site residues. The recombinant cel7482 was extremely tolerant to 2 M NaCl, suggesting that cel7482 may be a halotolerant cellulase. Moreover, the recombinant cel7482 was shown to have an ability to resist three ionic liquids (ILs), which are widely used for cellulose pretreatment. Furthermore, active cel7482 was secreted by the twin-arginine translocation (Tat) pathway of Bacillus subtilis 168 into the culture medium, which facilitates the subsequent purification and reduces the formation of inclusion body in the context of overexpression. CONCLUSIONS: This study demonstrated a simple and efficient method for direct cloning of new cellulase genes from environmental metagenomes. In the future, the metagenomics-guided strategy may be applied to the high-throughput screening of new cellulases from environmental metagenomes. PMID- 27382416 TI - Erratum to: Familial chromosomal translocation X; 22 associated with infertility and recurrent X mosaicism. AB - [This corrects the article DOI: 10.1186/s13039-016-0249-5.]. PMID- 27382417 TI - Comparing structural fingerprints using a literature-based similarity benchmark. AB - BACKGROUND: The concept of molecular similarity is one of the central ideas in cheminformatics, despite the fact that it is ill-defined and rather difficult to assess objectively. Here we propose a practical definition of molecular similarity in the context of drug discovery: molecules A and B are similar if a medicinal chemist would be likely to synthesise and test them around the same time as part of the same medicinal chemistry program. The attraction of such a definition is that it matches one of the key uses of similarity measures in early stage drug discovery. If we make the assumption that molecules in the same compound activity table in a medicinal chemistry paper were considered similar by the authors of the paper, we can create a dataset of similar molecules from the medicinal chemistry literature. Furthermore, molecules with decreasing levels of similarity to a reference can be found by either ordering molecules in an activity table by their activity, or by considering activity tables in different papers which have at least one molecule in common. RESULTS: Using this procedure with activity data from ChEMBL, we have created two benchmark datasets for structural similarity that can be used to guide the development of improved measures. Compared to similar results from a virtual screen, these benchmarks are an order of magnitude more sensitive to differences between fingerprints both because of their size and because they avoid loss of statistical power due to the use of mean scores or ranks. We measure the performance of 28 different fingerprints on the benchmark sets and compare the results to those from the Riniker and Landrum (J Cheminf 5:26, 2013. doi:10.1186/1758-2946-5-26) ligand based virtual screening benchmark. CONCLUSIONS: Extended-connectivity fingerprints of diameter 4 and 6 are among the best performing fingerprints when ranking diverse structures by similarity, as is the topological torsion fingerprint. However, when ranking very close analogues, the atom pair fingerprint outperforms the others tested. When ranking diverse structures or carrying out a virtual screen, we find that the performance of the ECFP fingerprints significantly improves if the bit-vector length is increased from 1024 to 16,384.Graphical abstractAn example series from one of the benchmark datasets. Each fingerprint is assessed on its ability to reproduce a specific series order. PMID- 27382418 TI - Evaluation of STAT medication ordering process in a community hospital. AB - BACKGROUND: In most health care facilities, problems related to delays in STAT medication order processing time are of common concern. OBJECTIVE: The purpose of this study was to evaluate processing time for STAT orders at Kimball Medical Center. METHODS: All STAT orders were reviewed to determine processing time; order processing time was also stratified by physician order entry (physician entered (PE) orders vs. non-physician entered (NPE) orders). Collected data included medication ordered, indication, time ordered, time verified by pharmacist, time sent from pharmacy, and time charted as given to the patient. RESULTS: A total of 502 STAT orders were reviewed and 389 orders were included for analysis. Overall, median time was 29 minutes, IQR 16-63; p<0.0001.). The time needed to process NPE orders was significantly less than that needed for PE orders (median 27 vs. 34 minutes; p=0.026). In terms of NPE orders, the median total time required to process STAT orders for medications available in the Automated Dispensing Devices (ADM) was within 30 minutes, while that required to process orders for medications not available in the ADM was significantly greater than 30 minutes. For PE orders, the median total time required to process orders for medications available in the ADM (i.e., not requiring pharmacy involvement) was significantly greater than 30 minutes. [Median time = 34 minutes (p<0.001)]. CONCLUSION: We conclude that STAT order processing time may be improved by increasing the availability of medications in ADM, and pharmacy involvement in the verification process. PMID- 27382419 TI - Role of the pharmacist in parenteral nutrition therapy: challenges and opportunities to implement pharmaceutical care in Kuwait. AB - BACKGROUND: Pharmacists can provide beneficial pharmaceutical care services to patients receiving Parenteral Nutrition (PN) therapy by working within Nutrition Support Teams (NSTs). OBJECTIVE: This study was designed to explore pharmacists' role in PN therapy in hospitals of Kuwait, sources of PN-related information, opinions on NSTs, perceptions about the barriers to pharmaceutical care implementation and views on how to enhance their practices. METHODS: Data were collected via face-to-face semi-structured interviews with the senior Total Parenteral Nutrition (TPN) pharmacists at all the hospitals which provide TPN preparation services (six governmental hospitals and one private hospital) in Kuwait. Descriptive statistics were used to describe pharmacists' demographic details and practice site characteristics. The interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: The pharmacists mainly performed technical tasks such as TPN compounding with minimal role in providing direct patient care. They used multiple different sources of TPN-related information to guide their practice. They reported positive and negative experiences with physicians depending on their practice environment. None of the hospitals had a functional NST. However, pharmacists expressed preference to work within NSTs due to the potential benefits of enhanced communication and knowledge exchange among practitioners and to improve service. Pharmacists perceived several barriers to providing pharmaceutical care including lack of reliable sources of TPN-related information, lack of a standard operating procedure for TPN across hospitals, insufficient staff, time constraints and poor communication between TPN pharmacists. To overcome these barriers, they recommended fostering pharmacists' education on TPN, establishing national standards for TPN practices, provision of pharmacy staff, development of NSTs, enhancing TPN pharmacists' communication and conducting TPN-research research. CONCLUSION: TPN pharmacists in Kuwait are confined to performing TPN manufacturing processes. There are promising avenues for future development of their role in patient care. This can be achieved by overcoming the barriers to pharmaceutical care practice and providing pharmacists with educational opportunities to equip them with the clinical competencies needed to practise as nutrition support pharmacists with patient-centred roles. PMID- 27382420 TI - Immunosuppressive serum levels in allogeneic hematopoietic stem cell transplantation: pharmaceutical care contribution. AB - BACKGROUND: Cyclosporine and tacrolimus are limited by a narrow therapeutic window. Maintaining immunosuppressive drugs at desired levels may be difficult. Pharmaceutical care emerges as a philosophy of practice that enhances medication use and leads to a better control of serum concentration. OBJECTIVE: This study aims to evaluate the impact of pharmaceutical care in the maintaining of proper serum levels of immunosuppressive medications in patients who have undergone allo HSCT. METHODS: The study had a quasi-experimental design that included a comparison group. The service model used was pharmacotherapy follow-up, according to an adaptation of the Dader method. The pharmacist consultation was carried out at a day-hospital or at the outpatient hematology clinic as needed. The intervention group consisted of 22 patients seen by a clinical pharmacist. The control group consisted of 44 patients that received standard care. This study aims to evaluate the impact of pharmaceutical care on keeping patient serum levels of cyclosporine and tacrolimus within the desired range. RESULTS: Control group displayed 65% of the proper serum levels of immunosuppressive agents. While In intervention group, the figure was 82% (p = 0.004). CONCLUSION: The role of the pharmacist in the multidisciplinary team may contribute to a greater success in attaining the patients' therapeutic targets with regard to the use of immunosuppressant. PMID- 27382421 TI - Redesigning pictographs for patients with low health literacy and establishing preliminary steps for delivery via smart phones. AB - BACKGROUND: Pictographs (or pictograms) have been widely utilized to convey medication related messages and to address nonadherence among patients with low health literacy. Yet, patients do not always interpret the intended messages on commonly used pictographs correctly and there are questions how they may be delivered on mobile devices. OBJECTIVE: Our objectives are to refine a set of pictographs to use as medication reminders and to establish preliminary steps for delivery via smart phones. METHODS: Card sorting was used to identify existing pictographs that focus group members found "not easy" to understand. Participants then explored improvements to these pictographs while iterations were sketched in real-time by a graphic artist. Feedback was also solicited on how selected pictographs might be delivered via smart phones in a sequential reminder message. The study was conducted at a community learning center that provides literacy services to underserved populations in Seattle, WA. Participants aged 18 years and older who met the criteria for low health literacy using S-TOFHLA were recruited. RESULTS: Among the 45 participants screened for health literacy, 29 were eligible and consented to participate. Across four focus group sessions, participants examined 91 commonly used pictographs, 20 of these were ultimately refined to improve comprehensibility using participatory design approaches. All participants in the fifth focus group owned and used cell phones and provided feedback on preferred sequencing of pictographs to represent medication messages. CONCLUSION: Low literacy adults found a substantial number of common medication label pictographs difficult to understand. Participative design processes helped generate new pictographs, as well as feedback on the sequencing of messages on cell phones, that may be evaluated in future research. PMID- 27382422 TI - Improving pediatric liquid medication labeling of the hospital information system in Malaysia: qualitative analysis of pharmacists' perceptions. AB - BACKGROUND: Inadequacies of drug labeling have been frequently reported among Malaysian healthcare institutes, in which the Hospital Information System (HIS) is used. OBJECTIVE: To identify potential areas to improve the existing labels used for pediatric liquid medications. METHODS: This study was qualitative in nature, whereby focus group discussions (FGDs), face-to-face interviews (FTFIs), and onsite observation were used for data collection. Pharmacists stationed at three units (outpatient, inpatient and clinical pharmacy) of a tertiary hospital were targeted. Both FGDs and FTFIs were facilitated using a semi-structured interview guide, video-recorded and transcribed verbatim. All transcripts were thematically analyzed using content analysis approach. RESULTS: Thirteen pharmacists participated in FGDs, while five were approached for FTFIs. Data analysis resulted in four major themes: format of labels, presentation of medication instructions, insufficiency of information, and the need for external aids and education. Participants unanimously agreed on the need for enlarging font sizes of key information. Suggestions were made to use more specific instructions for administration times and pictograms to illustrate important directions. The absence of information about storage, stability and handling of liquid medications was also highlighted. While discussion mainly focused on improving drug labeling, participants consistently stressed the need for an instruction sheet and pharmacist-based, one-to-one education regarding medication instructions. CONCLUSION: This study provides important insights into critical shortcomings in current labeling practice, underlying the need for developing a new label that incorporates a new format, additional information and pictograms for pediatric liquid medications. PMID- 27382423 TI - Patients' views on electronic patient information leaflets. AB - BACKGROUND: Information in society and in health care is currently undergoing a transition from paper to digital formats, and the main source of information will probably be electronic in the future. OBJECTIVE: To explore patients' use and perceptions of the patient information leaflet included in the medication package, and their attitude towards a transition to an electronic version. METHODS: The data was collected during October to November 2014 among individuals in South-Eastern Sweden, using a questionnaire (n=406, response rate 78%) and interviews (n=15). RESULTS: The questionnaire showed that the majority of the respondents (52%) occasionally read the patient information leaflet, 37% always read it, and 11% never read it. Almost half of the patients (41%) were positive towards reading the patient information leaflet electronically while 32% were hesitant and 26% neutral. A majority of the patients would request to get the patient information leaflet printed at the pharmacy if it was not included in the package. There were differences in attitude related to age and gender. The interviews showed that patients had mixed views on a transition to an electronic patient information leaflet. The patients perceived several positive aspects with an electronic patient information leaflet but were concerned about elderly patients. CONCLUSION: Although many were positive towards reading the patient information leaflet electronically, the majority prefer the patient information leaflet in paper form. Providing appropriate and useful eHealth services for patients to access the patient information leaflet electronically, along with education, could prepare patients for a transition to electronic patient information leaflet. PMID- 27382424 TI - Assessment and management of serotonin syndrome in a simulated patient study of Australian community pharmacies. AB - BACKGROUND: The incidence of serotonin syndrome is increasing due to the widening use of serotonergic drugs. Identification of serotonin syndrome is challenging as the manifestations are diverse. Misdiagnosis can lead to delay in care and inappropriate treatment. OBJECTIVES: The objectives of this study were to determine if staff of community pharmacies in Australia could identify the symptoms of serotonin syndrome in simulated patients and recommend an appropriate course of action. METHODS: Agents acting on behalf of a simulated patient were trained on a patient scenario that reflected possible serotonin syndrome due to an interaction between duloxetine and recently prescribed tramadol. They entered 148 community pharmacies in Australia to ask for advice about a 60 year old male simulated patient who was 'not feeling well'. The interaction was audio recorded and analysed for degree of access to the pharmacist, information gathered by pharmacy staff, management advice given and pharmacotherapy recommended. RESULTS: The simulated patient's agent was consulted by a pharmacist in 94.0% (139/148) of cases. The potential for serotonin syndrome was identified by 35.1% (52/148) of pharmacies. Other suggested causes of the simulated patient's symptoms were viral (16.9%; 25/148) and cardiac (15.5%; 23/148). A total of 33.8% (50/148) of pharmacies recommended that the simulated patient should cease taking tramadol. This advice always came from the pharmacist. Immediate cessation of tramadol was advised by 94.2% (49/52) of pharmacists correctly identifying serotonin syndrome. The simulated patient was advised to seek urgent medical care in 14.2% (21/148) of cases and follow up with a doctor when possible in 68.2% (101/148) of cases. The majority of pharmacies (87.8%; 130/148) did not recommend non-prescription medicines. CONCLUSION: While not identifying the cause of the simulated patient's symptoms in the majority of cases, community pharmacies recommended appropriate action to minimise the health impact of serotonin syndrome by advising to cease tramadol and/or referring to a doctor and not recommending non-prescription medicines to treat symptoms. Raising pharmacists' awareness of the signs and symptoms of serotonin syndrome, and the importance of taking a comprehensive medication history when assessing a set of symptoms, may help community pharmacies further reduce serotonin syndrome toxicity. PMID- 27382425 TI - Old age, high risk medication, polypharmacy: a 'trilogy' of risks in older patients with atrial fibrillation. AB - BACKGROUND: The safety of pharmacotherapy in atrial fibrillation (AF) is compounded by a trilogy of risks old age, high-risk medications (e.g., antithrombotics, antiarrhythmics), polypharmacy due to multiple patient comorbidities. However, to date, scarce study has investigated the use of polypharmacy (including potentially inappropriate medication (PIM)) in AF patients, and how this may contribute to their overall risk of medication misadventure. OBJECTIVES: To review the extent of polypharmacy and PIM use in older patients (65 years or older) with AF. METHODS: Information was extracted from a database characterising a cohort of older AF patients treated in general practice in New South Wales, Australia. Patient characteristics, number and types of drugs, the degree of PIM use were recorded. The predictors for the use of polypharmacy in older AF patients were identified. RESULTS: Overall, 367 patients (mean age 77.8 years) were reviewed, among which 94.8% used 5 medications or more and over half used 10 medications or more. Cardiovascular agents were most commonly used (98.9%), followed by antithrombotics (90.7%). Among agents deemed PIMs, digoxin (30.2%) was the most frequently used, followed by benzodiazepines (19.6%), and sotalol (9.8%). AF patients using polypharmacy were more likely to have low bleeding risk (OR=10.97), representing those patients in whom high-risk antithrombotics are mostly indicated. Patients with major-polypharmacy (5-9 medications) are more likely to have obstructive pulmonary diseases (OR=2.32), upper gastrointestinal diseases (OR=2.02) and poor physical function (OR=1.04), but less likely to have cognitive impairment (OR=0.27). CONCLUSION: Polypharmacy affects oldest AF patients, comprising medications that are indicated for AF, yet regarded as PIMs. Patients with lower risk of bleeding, obstructive pulmonary diseases, upper gastrointestinal diseases and poor physical function are also at higher risk of using higher number of medications. This may lead to an increased risk for medication misadventure due to the concomitant use of polypharmacy and medications for AF. PMID- 27382426 TI - Consumer access to clozapine in Australia: how does this compare to New Zealand and the United Kingdom? AB - BACKGROUND: Clozapine is an antipsychotic medication used in treatment resistant schizophrenia. However, clozapine is associated with a significant adverse effect profile and extensive monitoring is required to optimise consumer safety. Traditionally, clozapine can only be prescribed by a psychiatrist and dispensed at a hospital or hospital affiliated pharmacy in Australia. These restrictions could result in significant treatment burden for consumers taking clozapine. OBJECTIVE: To identify (1) the different models of supply that exist for people living in the community taking clozapine in Australia and compare to those in New Zealand and the United Kingdom, and (2) explore how these supply models may impact on consumer burden from the perspective of professionals involved in the supply of clozapine. METHOD: Key informants were interviewed (n=8) from Australia, New Zealand and the United Kingdom regarding how consumers, who lived in the community, accessed clozapine. Data were analysed and led to the development of four clozapine supply models. These four models were further validated by an online survey of a wider sample (n=30). Data were analysed thematically and via simple descriptive statistics. RESULTS: Clozapine supply varied depending on location. A secondary care model was utilised in the United Kingdom compared to a community based (primary care) model in New Zealand; Australia utilised a mixture of both secondary and primary care. A key theme from all study participants was that community pharmacy should be utilised to dispense clozapine to consumers living in the community, provided adequate training and safeguards are in place. It was noted that the utilisation of community pharmacies could improve access and flexibility, thereby reducing treatment burden for these consumers. CONCLUSION: There are predominately two models for supply of clozapine to consumers living in the community in Australia, New Zealand and the United Kingdom. One model utilises secondary care facilities and the other community services. Community pharmacy is ideally placed to increase access to clozapine for consumers living in the community, provided appropriate training and support is given to pharmacists providing this professional service. PMID- 27382428 TI - A qualitative study exploring medicines use pattern and practice among general public in Malaysia. AB - OBJECTIVE: The objective of this study is to explore the pattern and practice of medicine use among the general public; and to explore the key factors influencing medicine use among medicine users. METHODS: A qualitative approach using focus group discussions was conducted to get in-depth information about medicines use pattern and practice from the general public. Adult people who reported using medicines at the time of study or in the previous month were approached. Two focus group discussions were audio-recorded and transcribed verbatim. The obtained data were analysed using thematic content analysis. RESULTS: This study found that there are some misunderstanding about the appropriate use of medicines. The majority of the participants reported that they were complying with their medication regimen. However, forgetting to take medicines was stated by 4 participants while 2 participants stopped taking medicines when they felt better. In addition, 10 participants reporting using medicines according to their own knowledge and past experience. Whereas 4 participants took medicines according to other informal resources such as family, friends or the media. Seven participants have experienced side effects with using medicines, 4 of them informed their doctor while 3 participants stopped taking medicines without informing their doctor. CONCLUSION: There was a misunderstanding about medicines use in terms of medication compliance, self-management of the illness and the resources of information about using medicines. Many efforts are still needed from health care professionals to provide sufficient information about medicines use in order to decrease the risk of inappropriate use of medicines and to achieve better therapeutic outcome. PMID- 27382427 TI - Implementation and evaluation of a pharmacist-led hypertension management service in primary care: outcomes and methodological challenges. AB - BACKGROUND: Suboptimal utilisation of pharmacotherapy, non-adherence to prescribed treatment, and a lack of monitoring all contribute to poor blood (BP) pressure control in patients with hypertension. OBJECTIVE: The objective of this study was to evaluate the implementation of a pharmacist-led hypertension management service in terms of processes, outcomes, and methodological challenges. METHOD: A prospective, controlled study was undertaken within the Australian primary care setting. Community pharmacists were recruited to one of three study groups: Group A (Control - usual care), Group B (Intervention), or Group C (Short Intervention). Pharmacists in Groups B and C delivered a service comprising screening and monitoring of BP, as well as addressing poor BP control through therapeutic adjustment and adherence strategies. Pharmacists in Group C delivered the shortened version of the service. RESULTS: Significant changes to key outcome measures were observed in Group C: reduction in systolic and diastolic BPs at the 3-month visit (P<0.01 and P<0.01, respectively), improvement in medication adherence scores (P=0.01), and a slight improvement in quality of life (EQ-5D-3L Index) scores (P=0.91). There were no significant changes in Group B (the full intervention), and no differences in comparison to Group A (usual care). Pharmacists fed-back that patient recruitment was a key barrier to service implementation, highlighting the methodological implications of screening. CONCLUSION: A collaborative, pharmacist-led hypertension management service can help monitor BP, improve medication adherence, and optimise therapy in a step wise approach. However, blood pressure screening can effect behaviour change in patients, presenting methodological challenges in the evaluation of services in this context. PMID- 27382429 TI - Salvianolic Acid B Prevents Iodinated Contrast Media-Induced Acute Renal Injury in Rats via the PI3K/Akt/Nrf2 Pathway. AB - Contrast-induced acute renal injury (CI-AKI) has become a common cause of hospital-acquired renal failure. However, the development of prophylaxis strategies and approved therapies for CI-AKI is limited. Salvianolic acid B (SB) can treat cardiovascular-related diseases. The aim of the present study was to assess the effect of SB on prevention of CI-AKI and explore its underlying mechanisms. We examined its effectiveness of preventing renal injury in a novel CI-AKI rat model. Compared with saline, intravenous SB pretreatment significantly attenuated elevations in serum creatinine and the histological changes of renal tubular injuries, reduced the number of apoptosis-positive tubular cells, activated Nrf2, and lowered the levels of renal oxidative stress induced by iodinated contrast media. The above renoprotection of SB was abolished by the PI3K inhibitor (wortmannin). In HK-2 cells, SB activated Nrf2 and decreased the levels of oxidative stress induced by hydrogen peroxide and subsequently improved cell viability. The above cytoprotection of SB was blocked by the PI3K inhibitor (wortmannin) or siNrf2. Thus, our results demonstrate that, due to its antioxidant properties, SB has the potential to effectively prevent CI-AKI via the PI3K/Akt/Nrf2 pathway. PMID- 27382430 TI - The complete genome sequence and analysis of vB_VorS-PVo5, a Vibrio phage infectious to the pathogenic bacterium Vibrio ordalii ATCC-33509. AB - The bacterium Vibrio ordalii is best known as the causative agent of vibriosis outbreaks in fish and thus recognized for generating serious production losses in aquaculture systems. Here we report for the first time on the isolation and the genome sequencing of phage vB_VorS-PVo5, infectious to Vibrio ordalii ATCC 33509. The features as well as the complete genome sequence and annotation of the Vibrio phage are described; vB_VorS-PVo5 consists of a lineal double stranded DNA totaling ~ 80.6 Kb in length. Considering its ability to lyse Vibrio ordalii ATCC 33509, the phage is likely to gain importance in future aquaculture applications by controlling the pathogen and as such replacing antibiotics as the treatment of choice. PMID- 27382431 TI - Coevolution of neoplastic epithelial cells and multilineage stroma via polyploid giant cells during immortalization and transformation of mullerian epithelial cells. AB - Stromal cells are generally considered to be derived primarily from the host's normal mesenchymal stromal cells or bone marrow. However, the origins of stromal cells have been quite controversial. To determine the role of polyploidy in tumor development, we examined the fate of normal mullerian epithelial cells during the immortalization and transformation process by tracing the expression of SV40 large T antigen. Here we show that immortalized or HRAS-transformed mullerian epithelial cells contain a subpopulation of polyploid giant cells that grow as multicellular spheroids expressing hematopoietic markers in response to treatment with CoCl2. The immortalized or transformed epithelial cells can transdifferentiate into stromal cells when transplanted into nude mice. Immunofluorescent staining revealed expression of stem cell factors OCT4, Nanog, and SOX-2 in spheroid, whereas expression of embryonic stem cell marker SSEA1 was increased in HRAS-transformed cells compared with their immortalized isogenic counterparts. These results suggest that normal mullerian epithelial cells are intrinsically highly plastic, via the formation of polyploid giant cells and activation of embryonic stem-like program, which work together to promote the coevolution of neoplastic epithelial cells and multiple lineage stromal cells. PMID- 27382432 TI - The PI3K inhibitor taselisib overcomes letrozole resistance in a breast cancer model expressing aromatase. AB - Letrozole is a commonly used treatment option for metastatic hormone receptor positive (HR+) breast cancer, but many patients ultimately relapse. Due to the importance of phosphoinositide-3 kinase (PI3K) in breast cancer, PI3K inhibitors such as taselisib are attractive for combination with endocrine therapies such as letrozole. Taselisib was evaluated as a single agent and in combination with letrozole in a breast cancer cell line engineered to express aromatase. The combination of taselisib and letrozole decreased cellular viability and increased apoptosis relative to either single agent. Signaling cross-talk between the PI3K and ER pathways was associated with efficacy for the combination. In a secreted factor screen, multiple soluble factors, including members of the epidermal and fibroblast growth factor families, rendered breast cancer cells non-responsive to letrozole. It was discovered that many of these factors signal through the PI3K pathway and cells remained sensitive to taselisib in the presence of the soluble factors. We also found that letrozole resistant lines have elevated PI3K pathway signaling due to an increased level of p110alpha, but are still sensitive to taselisib. These data provide rationale for clinical evaluation of PI3K inhibitors to overcome resistance to endocrine therapies in ER+ breast cancer. PMID- 27382433 TI - Decreased expression of let-7c is associated with non-response of muscle-invasive bladder cancer patients to neoadjuvant chemotherapy. AB - The identification and development of biomarkers which predict response of muscle invasive bladder cancer (MIBC) patients to neoadjuvant chemotherapy would likely increase usage of this treatment option and thereby improve patient survival rates. MiRNA array and qRT-PCR validation was used to identify miRNA which are associated with response to neoadjuvant chemotherapy. RNA was extracted from a total of 41 archival, fully annotated, MIBC patient diagnostic biopsies (20 chemo responders and 21 non-responders (response is defined as > 5 year survival rate and being pT0 post-chemotherapy)). Microarray and qPCR identified let-7c as being differentially expressed in chemo-responder versus non-responder patients. Patients with higher let-7c expression levels had significantly higher odds of responding to chemotherapy (p = 0.023, OR 2.493, 95% CI 1.121, 5.546), and assessment of let-7c levels allowed for prediction of patient response (AUC 0.72, positive predictive value 59%). Decreased let-7c was associated with MIBC incidence (p < 0.001), and significantly correlated with other related miRNA including those that were not differentially expressed between responders and non responders. The combined data indicate let-7c plays a role in mediating chemoresistance to neoadjuvant chemotherapy in MIBC patients, and is a modest, yet clinically meaningful, predictor of patient response. PMID- 27382434 TI - The adenoviral E1A N-terminal domain represses MYC transcription in human cancer cells by targeting both p300 and TRRAP and inhibiting MYC promoter acetylation of H3K18 and H4K16. AB - Human cancers frequently arise from increased expression of proto-oncogenes, such as MYC and HER2. Understanding the cellular pathways regulating the transcription and expression of proto-oncogenes is important for targeted therapies for cancer treatment. Adenoviral (Ad) E1A 243R (243 aa residues) is a viral oncoprotein that interacts with key regulators of gene transcription and cell proliferation. We have shown previously that the 80 amino acid N-terminal transcriptional repression domain of E1A 243R (E1A 1-80) can target the histone acetyltransferase (HAT) p300 and repress HER2 in the HER2-overexpressing human breast cancer cell line SKBR3. Expression of E1A 1-80 induces death of SKBR3 and other cancer cell lines. In this study, we performed total cell RNA sequence analysis and identified MYC as the regulatory gene for cellular proliferation most strongly repressed by E1A 1-80. By RT-quantitative PCR analysis we show that repression of MYC in SKBR3 cells occurs early after expression of E1A 1-80, suggesting that MYC may be an early responder of E1A 1-80-mediated transcriptional repression. Of interest, while E1A 1-80 repression of MYC occurs in all eight human cancer cell lines examined, repression of HER2 is cell-type dependent. We demonstrate by ChIP analysis that MYC transcriptional repression by E1A 1-80 is associated with inhibition of acetylation of H3K18 and H4K16 on the MYC promoter, as well as inhibition of RNA Pol II binding to the MYC promoter. Deletion mutant analysis of E1A 1-80 suggests that both p300/CBP and TRRAP are involved in E1A 1-80 repression of MYC transcription. Further, E1A 1-80 interaction with p300/CBP and TRRAP is correlated with inhibition of H3K18 and H4K16 acetylation on the MYC promoter, respectively. Our results indicate that E1A 1-80 may target two important pathways for histone modification to repress transcription in human cancer cells. PMID- 27382436 TI - FGF19 functions as autocrine growth factor for hepatoblastoma. AB - Hepatoblastoma is the most common liver cancer in children, accounting for over 65% of all childhood liver malignancies. Hepatoblastoma is distinct from adult liver cancer in that it is not associated with hepatitis virus infection, cirrhosis, or other underlying liver pathology. The paucity of appropriate cell and animal models has been hampering the mechanistic understanding of hepatoblastoma pathogenesis. Consequently, there is no molecularly targeted therapy for hepatoblastoma. To gain insight into cytokine signaling in hepatoblastoma, we employed mass spectrometry to analyze the proteins secreted from Hep293TT hepatoblastoma cell line we established and identified the specific secretion of fibroblast growth factor 19 (FGF19), a growth factor for liver cells. We determined that silencing FGF19 by shRNAs or neutralizing secreted FGF19 by anti-FGF19 antibody inhibits the proliferation of hepatoblastoma cells. Furthermore, blocking FGF19 signaling by an FGF receptor kinase inhibitor suppressed hepatoblastoma growth. RNA expression analysis in hepatoblastoma tumors revealed that the high expression of FGF19 signaling pathway components as well as the low expression of FGF19 signaling repression targets correlates with the aggressiveness of the tumors. These results suggest the role of FGF19 as autocrine growth factor for hepatoblastoma. PMID- 27382435 TI - MUC16 contributes to the metastasis of pancreatic ductal adenocarcinoma through focal adhesion mediated signaling mechanism. AB - MUC16, a heavily glycosylated type-I transmembrane mucin is overexpressed in several cancers including pancreatic ductal adenocarcinoma (PDAC). Previously, we have shown that MUC16 is significantly overexpressed in human PDAC tissues. However, the functional consequences and its role in PDAC is poorly understood. Here, we show that MUC16 knockdown decreases PDAC cell proliferation, colony formation and migration in vitro. Also, MUC16 knockdown decreases the tumor formation and metastasis in orthotopic xenograft mouse model. Mechanistically, immunoprecipitation and immunofluorescence analyses confirms MUC16 interaction with galectin-3 and mesothelin in PDAC cells. Adhesion assay displayed decreased cell attachment of MUC16 knockdown cells with recombinant galectin-1 and galectin 3 protein. Further, CRISPR/Cas9-mediated MUC16 knockout cells show decreased tumor-associated carbohydrate antigens (T and Tn) in PDAC cells. Importantly, carbohydrate antigens were decreased in the region that corresponds to MUC16 and suggests for the decreased MUC16-galectin interactions. Co-immunoprecipitation also revealed a novel interaction between MUC16 and FAK in PDAC cells. Interestingly, we observed decreased expression of mesenchymal and increased expression of epithelial markers in MUC16-silenced cells. Additionally, MUC16 loss showed a decreased FAK-mediated Akt and ERK/MAPK activation. Altogether, these findings suggest that MUC16-focal adhesion signaling may play a critical role in facilitating PDAC growth and metastasis. PMID- 27382437 TI - Epigenetically silenced GNG4 inhibits SDF1alpha/CXCR4 signaling in mesenchymal glioblastoma. AB - The most common and aggressive form of primary brain tumor in adults is glioblastoma (GBM). From the global DNA methylation profiling study, previously published from our laboratory, we identified Guanine Nucleotide binding-protein Gamma subunit 4 (GNG4) to be one of the most hyper methylated and down regulated genes in GBM. GBM derived cell lines showed reduced GNG4 transcript levels, which could be reversed by methylation inhibitor treatment. Bisulphite sequencing confirmed the methylation status in glioblastoma tumor tissue and GBM derived cell lines. Overexpression of GNG4 was found to inhibit proliferation and colony formation of GBM cell lines and in vitro transformation of immortalized human astrocytes, thus suggesting a potential tumor suppressor role of GNG4 in GBM. Correlation of GNG4 transcript levels with that of all GPCRs from TCGA data revealed chemokine receptors as the potential target of GNG4. Furthermore, exogenous over expression of GNG4 inhibited SDF1alpha/CXCR4-dependent chemokine signaling as seen by reduced pERK and pJNK and GBM cell migration. The inhibitory association between GNG4 and SDF1alpha/CXCR4 was more evident in mesenchymal subtype of GBM. Thus, this study identifies GNG4 as an inhibitor of SDF1alpha/CXCR4-dependent signaling and emphasizes the significance of epigenetic inactivation of GNG4 in glioblastoma, especially in mesenchymal subtype. PMID- 27382438 TI - The Effect of Prophylactic Antibiotics on Post Laparoscopic Cholecystectomy Infectious Complications: A Double-Blinded Clinical Trial. AB - BACKGROUND: Laparoscopic cholecystectomy (LC) is one of the most common surgeries in laparoscopic surgery. Although, it is believed that LC has low-risk for post operative infectious complications, the use of a prophylactic antibiotic is still controversial in elective LC. OBJECTIVE: To determine the impact of prophylactic antibiotics on postoperative infection complications in elective laparoscopic cholecystectomy. METHODS: In this double-blind, placebo-controlled, randomized, clinical trial, patients who were candidates for elective LC, from March 2012 to 2015, in four hospitals in Babol, Iran, were studied. Patients were allocated randomly to two groups, i.e., group C: Cefazolin (n = 182) and group P: placebo (n = 247). Group C received 1 g of Cefazolin 30 minutes before anesthesia and and then, six and 12 hours after anesthesia. Group P patients received 10 ml of isotonic sodium chloride solution. Age, gender, type of gallbladder diseases (stone, polyp, or hydrops), the length of post-operative hospitalization, frequency of gallbladder rupture, the duration of surgery, and the kinds of complications associated with infections were collected for each patient in the two groups. The data were analyzed by IBM-SPSS version 20, using the t-test and the chi-squared test, and a p-value < 0.05 was considered as significant. RESULTS: There were no significant differences between the two groups in terms of gender (C versus P: 18 (9.9%) male versus 22 (9%); p = 0.74), age (C versus P: 43.75 + 13.30 years versus 40.91 + 13.05; p = 0.20), and duration of surgery (C versus P: 34.97 +/- 8.25 min versus 34.11 +/- 8.39; p = 0.71). There were no significant differences between the two groups in the incidences of post operative infection (C versus P: 3 (1.7%) versus 5 (2%); p = 0.99) and rupture of the gallbladder (C versus P: 14 (7.8%) versus 17 (6.8%); p = 0.85). No other post operative systemic infectious complications (e.g., sepsis, pneumonia, or urinary tract infection) were found in either group. CONCLUSION: For patients who underwent laparoscopic cholecystectomy (LC), prophylactic antibiotics had no important role in the prevention of infections; so these antibiotics apparently are not necessary in treatment, and they are not recommended for patients with laparoscopic cholecystectomy as low-risk selective antibiotics. TRIAL REGISTRATION: The trial was registered at the Iranian Clinical Trial Registry (http://www.irct.ir) with the IRCT identification number IRCT2013070413865N1. FUNDING: This research was supported financially by the Research Council of Babol University of Medical Sciences. PMID- 27382439 TI - Comparing the effects of treatment with sildenafil and cognitive-behavioral therapy on treatment of sexual dysfunction in women: a randomized controlled clinical trial. AB - BACKGROUND: Sexual dysfunction in women is prevalent and common in women after menopause. Many attempts to treat patients with sexual dysfunction by cognitive behavioral therapy (CBT) methods. But to the best of our knowledge, there has been no study that compared these two methods. OBJECTIVE: The aim of this study was to assess and compare the effects of sildenafil and cognitive-behavioral therapy on treatment of sexual dysfunction in women. METHODS: In this randomized, controlled, clinical trial, 86 women with arousal and orgasm dysfunction were surveyed. The patients were divided into two groups, i.e., sildenafil and CBT groups. The patients in the sildenafil group were treated by 50 mg of oral sildenafil one hour before intercourse, and the other group had weekly sessions of CBT for eight weeks. Sexual dysfunctions were evaluated by the Female Sexual Function Index (FSFI), a sexual satisfaction questionnaire, and the Enrich marital satisfaction scale. RESULTS: The mean age of the participants was 33.14 +/- 7.34 years. The mean scores for female sexual function index, sexual satisfaction, and the Enrich marital satisfaction scale were increased in both groups during treatment (p < 0.001). It was found that cognitive-behavioral therapy compared to treatment with sildenafil increased all subscales, except arousal, orgasm, and lubrication. CONCLUSION: Cognitive-behavioral therapy is more effective than treatment with sildenafil for improving female sexual function. CLINICAL TRIAL REGISTRATION: The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT2014070318338N1. FUNDING: The authors received no financial support for the research, authorship, and/or publication of this article. PMID- 27382441 TI - Components that affect the Implementation of Health Services' Strategic Purchasing: A Comprehensive Review of the Literature. AB - INTRODUCTION: Strategic purchasing is one of the mechanisms that can increase access, equity, and efficiency as well as the correct management of health resources. The aim of this study was to extract important and influential factors as necessary infrastructures to implement this method. METHODS: In this comprehensive literature review, 13 databases and search engines were searched from 2000 to 2015 by applying appropriate keywords. From a total of 1403 titles and after ensuring the validity of the study by the Clinical Appraisal Skills Program (CASP) tool, 18 articles that contained title, abstract, and associated text were used in the study, and their related information was analyzed and extracted using an extraction form and LitAssist software. RESULTS: The findings showed six categories of intervention have been effective in the strategic purchasing of all health interventions in different countries. These six categories were "The target group of users of the service" (demand side), "purchased interventions," "providers and suppliers of interventions" (the supply side), "Methods and incentives" (payment method), "price," and "Structure and organization." CONCLUSION: Although the necessity of performing strategic purchasing in the health sector or developing countries is an indisputable fact, it is of great importance to use the experiences of developed countries while considering the factors extracted from the study for implementing this method. In this regard, it is suggested that studies be performed that can lead to assessing the feasibility of strategic purchasing for health services in developing countries and also in Iran to help health policy makers in these countries. PMID- 27382440 TI - A systematic review and meta-analysis of the application of platelet rich plasma in sports medicine. AB - INTRODUCTION: In recent years, platelet rich plasma (PRP) has been receiving increasing attention for the treatment of soft tissue injuries. These numerous applications have raised a great deal of questions and debate about the effectiveness of this method. This study aimed to determine the efficacy of PRP in improving sports injuries and subsequently throw some light on these controversies. METHODS: A systematic review of the literature and meta-analysis of results were undertaken. All related databases, such as PubMed, Cochrane Database of Systematic Reviews, DARE, and EMBASE, were searched on the use of PRP on athletes and in sports medicine. The search was conducted from June 2013 to February 2014. RESULTS: Our search retrieved 905 studies, of which 13 randomized control trials (RCT) met our inclusion criteria for systematic review and meta analysis. All articles were appraised by Critical Appraisal Skills Program (CASP) checklist for RCT studies. The analysis of the results of pain scores and physical activity/functions did not show any superiority for PRP as opposed to the other options. CONCLUSIONS: The meta-analysis showed no more effectiveness for PRP application in sports-related injuries in terms of physical function improvement and pain relief. Therefore, the extensive use of PRP for such injuries should be limited. Well-designed RCTs are needed to support the findings. PMID- 27382442 TI - Relationship between Learning Style and Academic Status of Babol Dental Students. AB - INTRODUCTION: Identifying and employing students' learning styles could play an important role in selecting appropriate teaching methods in order to improve education. The aim of this study was to determine the relationship between the students' final exam scores and the learning style preferences of dental students at Babol University of Medical Sciences. METHODS: This cross-sectional study was conducted on 88 dental students studying in their fourth, fifth, and sixth years using the visual-aural-reading/writing-kinesthetic (VARK) learning styles' questionnaire. The data were analyzed with IBM SPSS, version 21, using the chi squared test and the t-test. RESULTS: Of the 88 participants who responded to the questionnaire, 87 preferred multimodal learning styles. There was no significant difference between the mean of the final exam scores in students who did and did not prefer the aural learning style (p = 0.86), the reading/writing learning style (p = 0.20), and the kinesthetic learning style (p = 0.32). In addition, there was no significant difference between the scores on the final clinical course among the students who had different preferences for learning style. However, there was a significant difference between the mean of the final exam scores in students with and without visual learning style preference (p = 0.03), with the former having higher mean scores. There was no significant relationship between preferred learning styles and gender (p > 0.05). CONCLUSION: The majority of dental students preferred multimodal learning styles, and there was a significant difference between the mean of the final exam scores for students with and without a preference for the visual learning style. In addition, there were no differences in the preferred learning styles between male and female students. PMID- 27382443 TI - Impact of Training High School Female Students in Ahvaz, Iran in the Social Skills Required to Avoid the Use of Drugs. AB - INTRODUCTION: Gender composition and the soaring trends of drug and tobacco dependency reveal the priority of social skills training related to drug avoidance self-efficacy among female students. The aim of this study was to verify the impact training high school female students to have the social skills needed to avoid the use of drugs. METHODS: This study was conducted from September 2012 to May 2013 in two high schools in Ahvaz City in southwest Iran. The participants were divided randomly into two groups of 60 students, one experimental group and one control group using the multi-stage simple sampling method. Two questionnaires, i.e. the ASES and TISS questionnaires, were completed before and after the intervention. Descriptive statistics, chi squared, paired samples t-test, and the independent-samples t-test were used. RESULTS: The participants had a mean age of 14.93 years. Among the 120 participants, 90.8% indicated that they had never smoked a cigarette, and 51.7% of the participants denied having smoked a hookah. There was no significant relationship between the self-sufficiency means of drug avoidance in the two groups of girls before intervention (p >= 0.05). However, after intervention, a significant difference was found in test score of self-efficacy of drug avoidance between the two groups, i.e., 94.91 +/- 8.3 for the control group versus 99.16 +/- 3.8 for the experimental group, p < 0.05). Significant increases were observed for the pre- and post-test scores of self-efficacy of drug avoidance in the experimental group compared to the control group (99.16 +/- 3.8 (p = 0.001) vs. 96.58 +/- 6.98 (p > 0.05). The mean values of the pre- and post-test scores of social skill before and after intervention increased significantly only for the experimental group (97.60 +/- 19.19 vs. 100.58 +/- 12.37, p = 0.03). CONCLUSION: Educational intervention can significantly enhance social skills for drug avoidance self efficacy, so it is recommended that such skills be taught in the high school curriculum. PMID- 27382444 TI - Comparison of Surface Hardness of Various Shades of Twinky Star Colored Compomer Light-cured with QTH and LED Units. AB - INTRODUCTION: Colored compomers are a group of restorative materials that were introduced in 2002 to repair primary teeth, and they provide attractive color and ease of use in pediatric dentistry. The aim of this study was to evaluate the effect of QTH and LED light-curing units on the surface hardness of different colors of Twinky Star compomers. METHODS: In this experimental study, a composite resin (Z250, 3M, and USA), an ionosit compomer (DMG, Germany) with A3 shade and 8 different Twinky Star colored compomer (Voco, Germany) samples were used. In all, 100 samples were prepared with 10 samples in each group, i.e., 10 Z250 composite resin, 10 ionosit compomers, and 10 Twinky Star compomer samples of each color. The samples were prepared in a 4*4-mm Teflon mold. Half of the samples were light cured with QTH and the other half with LED units. Then, the surface microhardness was measured by Vickers hardness test. The data were analyzed with IBM-SPSS version 22, using the t-test and ANOVA. RESULTS: Two-way ANOVA showed that the mean surface hardness of the compomer samples cured with the QTH unit was significantly higher than that cured with the LED unit (p < 0.001). In each curing unit, surface hardness of some materials exhibited significant differences with the highest hardness being observed in the Z250 composite resin (650.35 +/- 56.320) and the lowest hardness being detected in the ionosit compomers (461.10 +/- 96.170). One-way ANOVA also showed that, among the different colors of the Twinky Star compomer, the lowest hardness with both units (QTH and LED) was observed in the gold color (214.32 +/- 22.026 and 175.116 +/- 15.918, respectively). CONCLUSION: The colored compomer and the type of light-curing unit affected the microhardnesses of the surfaces. Different colors of Twinky Star compomers exhibited different surface microhardnesses. PMID- 27382445 TI - Median Nerve Somatosensory Evoked Potential in HTLV-I Associated Myelopathy. AB - INTRODUCTION: HTLV-I Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a progressive Myelopathy that mainly involves the corticospinal tract. Despite pronounced involvement of the lower limbs, patients also have abnormalities in their upper limbs. So, we studied somatosensory-evoked potentials (SSEPs) of the median nerve in HAM/TSP patients to determine the extent of the involvement of the pathway of the central nervous system, especially the cervical spinal cord. METHODS: In this cross sectional study, 48 patients with HAM/TSP who were referred to Qaem Hospital in Mashhad from October 2010 to October 2011 were evaluated for various indices, including SSEPs of the median nerve for N9, N11, N13, and N20 waveforms and also N11-13 and N13-20 Inter Peak Latency (IPL), severity of disease (based on Osama criteria), disease duration (less or more than 2 years), age, and gender. SPSS software was used for data analysis. The t test was used for quantitative data, and the chi-squared test was used for the qualitative variables. RESULTS: Thirty-four patients (70.2%) were females. The mean age was 45.6 +/- 14.2 years. About SSEPs indices of the median nerve, N9 and N11 were normal in all patients, but N13 (50%), N20 (16.7%), IPL11-13 (58.3%), and IPL13-20 (22.9%) were abnormal. No significant relationships were found between age, gender, disease duration, and SSEPs indices (p > 0.05), but IPL11-13 and IPL13-20 had significant relationships with disease disability (p = 0.017 and p = 0.01, respectively). CONCLUSION: Despite the lack of obvious complaints of upper limbs, SSEPs indices of the median nerve from the cervical spinal cord to the cortex were abnormal, which indicated extension of the lesion from the thoracic spinal cord up to the cervical spinal cord and thalamocortical pathways. Also, abnormalities in the cervical spinal cord had a direct correlation with the severity of disability in patients with HAM/TSP. PMID- 27382446 TI - Awareness, knowledge, and attitude of dentistry students in Kerman towards evidence-based dentistry. AB - INTRODUCTION: Evidence-based care helps dentists provide quality dental services to patients, and such care is based on the use of reliable information about treatment and patient care from a large number of papers, books, and published textbooks. This study aimed to determine the knowledge, awareness, and attitude of dentistry students towards evidence-based dentistry. METHODS: In this cross sectional study, all dentistry students who were studying in their sixth semester and higher in the Kerman School of Dentistry (n = 73) were studied. The data were analyzed using SPSS version 17 and the independent-samples t-tests and the ANOVA test. RESULTS: The means of the students' knowledge, awareness, and attitude scores were 29.2 +/- 10.8, 29.9 +/- 8.12 and 44.5 +/- 5.3, respectively. Among demographic variables, only the number of semesters showed a significant difference with knowledge, awareness, and attitude of dentistry students toward evidence-based dentistry (p = 0.001). CONCLUSION: According to the results of this study, knowledge and awareness of dentistry students at Kerman University of Medical Sciences towards evidence-based dentistry were average and have a neutral attitude. Thus, providing necessary training in this regard will cause promoting the knowledge, awareness, and improved attitudes of dentistry students. PMID- 27382447 TI - The Impact of Hemodialysis on Sexual Function in Male Patients using the International Index of Erectile Function Questionnaire (IIEF). AB - INTRODUCTION: Routine hemodialysis is one of the preferred treatment methods in patients with chronic kidney disease. It seems that routine hemodialysis can be effective in improving sexual function in these patients. This study aimed to determine the effect of routine dialysis sessions over a six-month period on the status of sexual function in men with chronic renal failure using the International Index of Erectile Function (IIEF) questionnaire. METHODS: The cross sectional study was conducted from November 2015 to November 2016 on patients with chronic renal failure who were first-time candidates for routine hemodialysis and who were referred to Imam Reza Hospital of Mashhad. All of the patients completed the IIEF questionnaire before their first hemodialysis. Afterwards, all of the patients underwent routine dialysis sessions over a six month period and completed the IIEF questionnaire again at the end of the sixth month. The prevalence of sexual dysfunction was assessed before and after hemodialysis. The scores on the two IIEF questionnaires were compared according to five domains, i.e., erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction. The comparisons were done before and after hemodialysis using the paired-samples t-test. Statistical analyses were performed using SPSS version 19. RESULTS: The study included 30 men with a mean age of 40.2 +/- 8.2. The prevalence of sexual dysfunctions in the order of their frequency was as follows: intercourse satisfaction (100%), overall satisfaction (100%), sexual desire (96.7%), orgasmic function (93.3%), and erectile function (90%). After six months of treatment with hemodialysis, the ratings of all areas of sexual dysfunction were improved significantly (p-value = 0.00 for all domains). CONCLUSION: According to the results of this study, it seems that a six-month course of hemodialysis can improve erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction in patients with chronic kidney disease. PMID- 27382448 TI - Factors contributing towards patient's choice of a hospital clinic from the patients' and managers' perspective. AB - INTRODUCTION: Given the competitive nature of the health market and the multiplicity of factors that may contribute towards patient's choices of a hospital, patients' needs and preferences for a hospital must be considered in the planning and decision making of hospitals and health care organizations. This study aimed to identify the factors that contribute to patient's choices of a clinic and the importance of each factor. METHODS: A mixed-method approach was used to collect quantitative and qualitative data in two phases. The study was conducted in a hospital clinic in 2014. Qualitative data were collected by face to-face semi-structured interviews of a sample of 22 managers and heads of outpatient wards. The self-administered questionnaire designed for this study collected quantitative data from a stratified random sample of 381 patients referred to this clinic. The qualitative data were analyzed by a system of coding, while parametrical statistical analyses were conducted to analyze the quantitative data using the independent-samples t-test and ANOVA in SPSS software, version 21.0. RESULTS: The qualitative data indicated that there were 21 factors that may contribute to patient's choices of a clinic, and these factors were classified into six categories, i.e., facilities and physical assets, physicians and employees, location and place, services, price, and promotion. Among the 16 questions studied in the quantitative questionnaire, the highest and lowest means were related to "appropriate clinic environment" (2.47 +/- 0.58) and "advertising through TV and radio, the Internet, newspapers, etc." (1.77 +/- 0.75), respectively. There were significant associations between "having experienced and responsive personnel, including physicians and employees" and the patient's gender and frequency of referrals, between "belonging to the Armed Forces" and the patient's age and frequency of referrals, between "advertising through TV and radio, the Internet, newspapers, etc." and shifts and frequency of referrals, between "inadequate facilities and poor quality of services provided in other health care organizations of the Armed Forces" and "adornment and good behavior of staff" and shifts (p < 0.05). CONCLUSION: The most significant contributing factors to attract patients were the "physicians and employees," and "the clinic's environment." Therefore, it is essential for clinic managers and heads of outpatient wards to focus on and strengthen these two factors. Also, since the means of the factors were better in the morning shift, the employees should perform their duties properly and consistently in all shifts. PMID- 27382449 TI - Cluster analytical approach to Lifestyle characteristics: A population based study in Shiraz, Iran. AB - INTRODUCTION: A limited number of risky behaviors cause most morbidity and mortality. The aim of this study was to determine the possible clustering of lifestyle behaviors, including transportation behaviors, diet, physical activity, and smoking in Shiraz, Iran. METHODS: There were 776 representative Shirazi adults who participated in this cross-sectional study. The questionnaires were completed via person-to-person interviews. The datasets were searched for any clustering patterns. Cluster analysis was used for statistical analysis, and the data were analyzed using SPSS version 11.5. RESULTS: Three distinct clusters were identified. Cluster 1 was named "Healthy," and it included non-smokers, safe drivers, appropriate or acceptable fruit, vegetable, and fast-food consumers, and physically-active people. Cluster 2, "Moderately Healthy," was relatively risky drivers who had appropriate behaviors on the rest of the health-related behaviors. Cluster 3, "Unhealthy," was smokers, risky drivers, inappropriate or unacceptable fruit, vegetable & fast-food consumers, and a sedentary lifestyle. CONCLUSIONS: It was obvious that health-related behaviors were clustered together and unhealthy behaviors were not established in isolation. PMID- 27382450 TI - Competence of nurses in the intensive cardiac care unit. AB - INTRODUCTION: Competence of nurses is a complex combination of knowledge, function, skills, attitudes, and values. Delivering care for patients in the Intensive Cardiac Care Unit (ICCU) requires nurses' competences. This study aimed to explain nurses' competence in the ICCU. METHODS: This was a qualitative study in which purposive sampling with maximum variation was used. Data were collected through semi-structured interviews with 23 participants during 2012-2013. Interviews were recorded, transcribed verbatim, and analyzed by using the content analysis method. RESULTS: The main categories were "clinical competence," comprising subcategories of 'routine care,' 'emergency care,' 'care according to patients' needs,' 'care of non-coronary patients', as well as "professional competence," comprising 'personal development,' 'teamwork,' 'professional ethics,' and 'efficacy of nursing education.' CONCLUSION: The finding of this study revealed dimensions of nursing competence in ICCU. Benefiting from competence leads to improved quality of patient care and satisfaction of patients and nurses and helps elevate nursing profession, improve nursing education, and clinical nursing. PMID- 27382451 TI - Constraining Factors of Research among faculty members at Hormozgan University of Medical Sciences. AB - INTRODUCTION: In recent decades, the major criteria for development in countries were defined mostly by research position. The first step in organizing the research subject in societies is gaining a correct perception of abilities, available facilities, and finding the strengths and weaknesses of research programs. This research was conducted to determine the constraining factors of research among faculty members. METHODS: In this cross-sectional study in 2013, the population was Hormozgan Medical Science faculty members, and samples were selected based on the Morgan table (138 individuals). A researcher-made questionnaire after determining validity and confirming reliability was distributed among them. The data were analyzed by SPSS using descriptive and inferential statistics, such as Pearson's product-moment correlation. RESULTS: Among organizational factors, lack of data presentation to researchers from organization sections with 81.2% was the most effective factor. The lack of facilitating national and international research exchange with 80.5% and the lack of research workshops based on needs with 77.9% were the next ones. Among the personal constraining factors, 64% of the faculty declared that having inadequate time for research due to the educational activities was the main factor. CONCLUSIONS: According to the faculty's comments, research activities encounter different constraining factors. It can be said that, by promoting a data registration system, collaborating on contract agreements and improving national and international research exchange, empowering members' research (need-based workshops), and decreasing the faculty's clinical and educational activities can overcome these constraints. PMID- 27382452 TI - Ameliorative Effect of Vanillic Acid on Serum Bilirubin, Chronotropic and Dromotropic Properties in the Cholestasis-Induced Model Rats. AB - INTRODUCTION: The liver modulates several important roles, such as metabolism and liver cirrhosis, which have several cardiovascular problems. Due to preservative role of antioxidant agents in cardiovascular disease, consequently, many of them are applied as medicinal plants in traditional medicine. Vanillic acid (VA), as an antioxidant agent, has a principal preservative role on some diseases. In this study, the effect of vanillic acid was examined on heart rate (as chronotropic property), P-R interval (as dromotropic property), and serum bilirubin in cholestasis-induced model rats. METHODS: In this study, 32 male Sprague-Dawley rats weighing 200-250 g were allocated into four groups, and each group contained eight rats as follows: Control (normal saline, 1 ml/kg, gavage, daily for 4 weeks), cirrhotic (normal saline, 1 ml/kg, gavage, daily for 4 weeks), vanillic acid (10 mg/kg, gavage, daily for 4 weeks), cirrhotic treated with vanillic acid (10 mg/kg, gavage, daily for 4 weeks). Chronic biliary cirrhosis was induced in cirrhotic groups by four weeks Bile Duct Ligation (BDL). At the first day and four weeks after surgery, the animals were anesthetized, electrocardiograms were recorded (lead II), and chronotropic and dromotropic properties (HR and PR interval) were investigated. At the end of experimental duration, the animals were anesthetized, and blood samples were taken to measure serum bilirubin. The results were analyzed using t-test and one-way ANOVA by SPSS software, version 22. RESULTS: After induced of BDL, the results presented that laboratory parameter (bilirubin) in the cirrhotic group significantly increased compared to the control group. The P-R interval was reduced in the cirrhotic group compared to the control group, and there was no significant difference between heart rate in all groups. Bilirubin were reduced in cirrhotic groups treated with vanillic acid (VA) compared to cirrhotic group and also administration of VA in the cirrhotic treated with VA increased dromotropic property in comparison with the cirrhotic group. CONCLUSION: According to the results obtained in this study, preventing elevated bilirubin and increase dromotropic property in cirrhotic group taking the VA suggested that the consumption of vanillic acid as an antioxidant can be effective in the prevention of liver diseases. PMID- 27382453 TI - A Review of the Clinical Implications of Breast Cancer Biology. AB - BACKGROUND: Histologically similar tumors may have different prognoses and responses to treatment. These differences are due to molecular differences. Hence, in this review, the biological interaction of breast cancer in several different areas is discussed. In addition, the performance and clinical application of the most widely-recognized biomarkers, metastasis, and recurrences from a biological perspective and current global advances in these areas are addressed. OBJECTIVE: This review provides the performance and clinical application of the most widely-recognized biomarkers, metastasis, and recurrences from the biological perspective and current global advances in these areas. METHODS: PubMed, Scopus, and Google Scholar were searched comprehensively with combinations of the following keywords: "breast cancer," "biological markers," and "clinical." The definition of breast cancer, diagnostic methods, biological markers, and available treatment approaches were extracted from the literature. RESULTS: Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), and Ki-67 are the most well-known biological markers that have important roles in prognosis and response to therapeutic methods. Some studies showed the response of ER-positive and PR-negative tumors to anti-estrogenic treatment to be lower than ER-positive and PR-positive tumors. Patients with high expression of HER-2 and Ki-67 had a poor prognosis. In addition, recent investigations indicated the roles of new biomarkers, such as VEGF, IGF, P53 and P21, which are associated with many factors, such as age, race, and histological features. CONCLUSION: The objective of scientists, from establishing a relationship between cancer biology infrastructures with clinical manifestations, is to find new ways of prevention and progression inhibition and then possible introduction of less dangerous and better treatments to resolve this dilemma of human society. PMID- 27382454 TI - Iron chelation monotherapy in transfusion-dependent beta-thalassemia major patients: a comparative study of deferasirox and deferoxamine. AB - INTRODUCTION: Iron overload is the primary cause of mortality and morbidity in thalassemia major (TM) despite advances in chelation therapy. The aim of this study was to compare the effectiveness and safety of deferasirox (DFX) and deferoxamine (DFO) as iron-chelating agents in patients with transfusion dependent beta-thalassemia major. METHODS: This prospective randomized study included 60 patients with transfusion-dependent beta-TM during the period from September 2014 to September 2015. Their ages were >= 6 years, and they had serum ferritin above 1500 MUg/L and were on irregular DFO therapy. Patients had regular packed red cell transfusion in a dose of 10 mL/kg/session. They were randomized to receive DFX (single oral daily dose of 20-40 mg/kg/day) or DFO (20-50 mg/kg/day via subcutaneous infusion over 8-10 hours, 5 days a week). Iron overload was determined by serum ferritin level. The primary endpoint was decrease of serum ferritin level below 1500 MUg/L. The secondary endpoint was drug safety. RESULTS: Both drugs significantly reduced serum ferritin (p < 0.001). At the end of follow-up, there were no significant differences between the two groups in serum ferritin levels (p = 0.673) and in percent reduction of ferritin (p = 0.315). There were no significant differences between the two groups in the total amount of blood transfusion (p = 0.166) and average iron intake (p = 0.227). There were no mortalities or any serious adverse effects, neutropenia, arthropathy, or pulmonary toxicity. Gastrointestinal upset and skin rash occurred more frequently with DFX than with DFO (p = 0.254 and 0.095, respectively). CONCLUSION: With appropriate dosing and compliance with drugs, both DFX and DFO are generally well tolerated, safe, and effective in reducing serum ferritin levels in iron-overloaded, regularly-transfused thalassemia major patients. Therefore, oral DFX is recommended for more convenience and adherence to the treatment regimen. PMID- 27382455 TI - Impact of morphine use in reducing the need for CT scan in patients with cervical spine trauma: a double blinded randomized clinical trial. AB - BACKGROUND: Cervical spine trauma occurs mostly among young males due to falls and car accidents. The CT scan technology is replacing radiography in many medical clinics as it is very capable in detecting subtle cervical spine injuries. However, the use of CT scan for routine screening in patients with cervical spine trauma remains controversial due to its radiation risks and relatively high cost. OBJECTIVE: The focus of this research was on using morphine in patients with cervical spine trauma. The objective was to determine the ability of morphine to reduce the number of patients in need of CT scans. METHODS: This double-blinded randomized clinical trial study was conducted from April 2014 to March 2015 in Hasheminejad Hospital in Mashhad, Iran. We enrolled 67 patients with cervical spine trauma and normal radiography in the study. They were divided randomly into two groups (groups A and B), where group A received intravenous morphine, and group B received a placebo. We measured the pain scores in both groups before giving the medication and 10 minutes afterwards using a visual analog scale (VAS). RESULTS: As a result of receiving morphine, the patients in group A had significantly lower pain than group B (p-value < 0.001). The average pain score in group A was reduced by 43% versus 23% in group B. However, the most pain reduction was in those in group A with a normal CT scan. The pain score of these patients dropped by 52%. CONCLUSIONS: The findings of this study suggest that patients with a normal radiography may be discharged with a cervical collar without a need for a CT scan if morphine reduces their pain. This is because the pain in these patients stem from the muscles and non-bony structures in the cervical spine area. CLINICAL TRIAL REGISTRATION: The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT2013100214872N1. FUNDING: The authors received no financial support for the research or for the publication of this article. PMID- 27382456 TI - The impact of Silymarin on improvement of platelet abnormalities in patients with severe preeclampsia. AB - BACKGROUND: Preeclampsia is a pregnancy-specific disorder that is associated with an increase in blood pressure and proteinuria; in severe cases, it can cause platelet abnormalities. Silymarin is the extract of Silybum marianum, which is recognized as a safe antioxidant drug. OBJECTIVE: To determine the impact of Silymarin on the improvement of severe preeclampsia in 60 patients with severe preeclampsia. METHODS: In this double-blind clinical trial study, This study included 60 patients whose pregnancies were terminated because of severe preeclampsia and who were referred to Hajar Hospital in Shahrekord, Iran, from April 2014 to September 2015. The patients were divided randomly into two groups, i.e., a group of 30 patients and a control group of 30 patients. In addition to the current treatments for preeclampsia, The members of the study group were administered 70 mg of Silymarin at three hours and 24 hours after the termination of their pregnancies. The control group received a placebo at the same times. Platelet count tests were compared at the baseline and at 12, 36, and 60 hours post-measurements in the two groups by SPSS software, version 22, by the ANOVA test, and by the independent-samples t-test. RESULTS: At the baseline, the two groups were not significantly different in terms of various criteria, such as age, BMI, and platelet counts. There were no significant differences between the two groups regarding the number of platelets at 12, 36, and 60 h after their pregnancies were ended (p > 0.01). CONCLUSIONS: The results of this study indicated that, although oxidative factors are involved in the incidence of complications of preeclampsia, e.g., thrombocytopenia, merely using an oxidative agent does not alleviate this effect. This indicated that other factors likely are involved in the pathogenesis of this disease. Additional studies are needed to prove the beneficial effects of this drug in the treatment of preeclampsia. CLINICAL TRIAL REGISTRATION: The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the Irct ID: IRCT201509042388/N1. FUNDING: Shahrekord University of Medical Sciences supported this research (project no. 2006). PMID- 27382457 TI - A Novel Active Contour Model for MRI Brain Segmentation used in Radiotherapy Treatment Planning. AB - INTRODUCTION: Brain image segmentation is one of the most important clinical tools used in radiology and radiotherapy. But accurate segmentation is a very difficult task because these images mostly contain noise, inhomogeneities, and sometimes aberrations. The purpose of this study was to introduce a novel, locally statistical active contour model (ACM) for magnetic resonance image segmentation in the presence of intense inhomogeneity with the ability to determine the position of contour and energy diagram. METHODS: A Gaussian distribution model with different means and variances was used for inhomogeneity, and a moving window was used to map the original image into another domain in which the intensity distributions of inhomogeneous objects were still Gaussian but were better separated. The means of the Gaussian distributions in the transformed domain can be adaptively estimated by multiplying a bias field by the original signal within the window. Then, a statistical energy function is defined for each local region. Also, to evaluate the performance of our method, experiments were conducted on MR images of the brain for segment tumors or normal tissue as visualization and energy functions. RESULTS: In the proposed method, we were able to determine the size and position of the initial contour and to count iterations to have a better segmentation. The energy function for 20 to 430 iterations was calculated. The energy function was reduced by about 5 and 7% after 70 and 430 iterations, respectively. These results showed that, with increasing iterations, the energy function decreased, but it decreased faster during the early iterations, after which it decreased slowly. Also, this method enables us to stop the segmentation based on the threshold that we define for the energy equation. CONCLUSION: An active contour model based on the energy function is a useful tool for medical image segmentation. The proposed method combined the information about neighboring pixels that belonged to the same class, thereby making it strong to separate the desired objects from the background. PMID- 27382458 TI - Effects of the Effect of Ultra High Frequency Mobile Phone Radiation on Human Health. AB - INTRODUCTION: Public and occupational exposure to electromagnetic fields due to the growing trend of electronic devices may cause adverse effects on human health. This paper describes the risk of mutation and sexual trauma and infertility in masculine sexual cell by mobile phone radiations. METHODS: In this study, we measured the emitted dose from a radiofrequency device, such as switching high voltage at different frequencies using a scintillation detector. The switching high voltage power supply (HVPS) was built for the Single Photon Emission Computed Tomography (SPECT) system. For radiation dosimetry, we used an ALNOR scintillator that can measure gamma radiation. The simulation was performed by MATLAB software, and data from the International Commission on Non-Ionizing Radiation Protection (ICNIRP) were used to verify the simulation. RESULTS: We investigated the risks that result from the waves, according to a report by International Commission on Non Ionizing Radiation Protection (ICNIRP), to every organ of the body is defined by the beam and electromagnetic radiation from this electronic device on people. The results showed that the maximum personal dose over a 15-min period working at the mentioned HVPS did not exceed 0.31 MUSV/h (with an aluminum shield). So, according to other sources of radiation, continuous working time of the system should not be more than 10 hours. Finally, a characteristic curve for secure working with modules at different frequencies was reported. The RF input signal to the body for maximum penetration depth (delta) and electromagnetic energy absorption rate (SAR) of biological tissue were obtained for each tissue. CONCLUSION: The results of this study and International Commission of Non Ionization Radiation Protection (ICNIRP) reports showed the people who spend more than 50 minutes a day using a cell phone could have early dementia or other thermal damage due to the burning of glucose in the brain. PMID- 27382459 TI - Characterization of a Dmd (EGFP) reporter mouse as a tool to investigate dystrophin expression. AB - BACKGROUND: Dystrophin is a rod-shaped cytoplasmic protein that provides sarcolemmal stability as a structural link between the cytoskeleton and the extracellular matrix via the dystrophin-associated protein complex (DAPC). Mutations in the dystrophin-encoding DMD gene cause X-linked dystrophinopathies with variable phenotypes, the most severe being Duchenne muscular dystrophy (DMD) characterized by progressive muscle wasting and fibrosis. However, dystrophin deficiency does not only impair the function of skeletal and heart muscle but may also affect other organ systems such as the brain, eye, and gastrointestinal tract. The generation of a dystrophin reporter mouse would facilitate research into dystrophin muscular and extramuscular pathophysiology without the need for immunostaining. RESULTS: We generated a Dmd (EGFP) reporter mouse through the in frame insertion of the EGFP coding sequence behind the last Dmd exon 79, which is known to be expressed in all major dystrophin isoforms. We analyzed EGFP and dystrophin expression in various tissues and at the single muscle fiber level. Immunostaining of various members of the DAPC was done to confirm the correct subsarcolemmal location of dystrophin-binding partners. We found strong natural EGFP fluorescence at all expected sites of dystrophin expression in the skeletal and smooth muscle, heart, brain, and retina. EGFP fluorescence exactly colocalized with dystrophin immunostaining. In the skeletal muscle, dystrophin and other proteins of the DAPC were expressed at their correct sarcolemmal/subsarcolemmal localization. Skeletal muscle maintained normal tissue architecture, suggesting the correct function of the dystrophin-EGFP fusion protein. EGFP expression could be easily verified in isolated myofibers as well as in satellite cell-derived myotubes. CONCLUSIONS: The novel dystrophin reporter mouse provides a valuable tool for direct visualization of dystrophin expression and will allow the study of dystrophin expression in vivo and in vitro in various tissues by live cell imaging. PMID- 27382460 TI - Allergen immunotherapy for IgE-mediated food allergy: protocol for a systematic review. AB - BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated food allergy. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in IgE-mediated food allergy. METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. DISCUSSION: The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT. PMID- 27382461 TI - Drosophila melanogaster as a model for basal body research. AB - The fruit fly, Drosophila melanogaster, is one of the most extensively studied organisms in biological research and has centrioles/basal bodies and cilia that can be modelled to investigate their functions in animals generally. Centrioles are nine-fold symmetrical microtubule-based cylindrical structures required to form centrosomes and also to nucleate the formation of cilia and flagella. When they function to template cilia, centrioles transition into basal bodies. The fruit fly has various types of basal bodies and cilia, which are needed for sensory neuron and sperm function. Genetics, cell biology and behaviour studies in the fruit fly have unveiled new basal body components and revealed different modes of assembly and functions of basal bodies that are conserved in many other organisms, including human, green algae and plasmodium. Here we describe the various basal bodies of Drosophila, what is known about their composition, structure and function. PMID- 27382462 TI - Erratum to: Respiratory consequences of N95-type Mask usage in pregnant healthcare workers-a controlled clinical study. AB - [This corrects the article DOI: 10.1186/s13756-015-0086-z.]. PMID- 27382463 TI - High bacterial load of indoor air in hospital wards: the case of University of Gondar teaching hospital, Northwest Ethiopia. AB - BACKGROUND: The air inhaled by people is abundantly populated with microorganisms which also are called bioaerosols. Bioaerosols is a colloidal suspension, formed by liquid droplets and particles of solid matter in the air, whose components contain or have attached to them viruses, fungal spores and conidia, bacterial endospores, plant pollen and fragments of plant tissues. They account for 5-34 % of indoor air pollution. METHODS: A cross-sectional study was conducted to assess the bacteriological concentration and to identify specific species of bacteria in the indoor air of Gondar University teaching hospital. Air samples were taken from 14 randomly selected wards. Bacterial measurements were made by passive air sampling technique i.e., the settle plate method. In each ward five Petri dishes were exposed for 30 and 60 min in the morning and afternoon. Bacteria were collected on nutrient agar and blood agar media. Both quantitative and qualitative analyses were conducted. The quantitative analysis was mainly conducted to determine bacterial load or number of bacteria in the indoor air. Bacterial load was enumerated as colony forming units. Qualitative analysis was conducted to identify specific species of bacteria. For this study we have selected Staphylococcus aureus and Streptococcus which had high public health concern. Mannitol test was used to isolate Staphylococcus aureus, whereas Bacitracin test was conducted to isolate Streptococcus pyogene. RESULT: The result of this study indicated that the highest bacterial load which was 1468 CFU/m(3) has been recorded at 2:00 PM in Ward C at 60 min exposure time and the lowest bacterial concentration (i.e., 480 CFU/m(3)) was recorded at 8:00 AM in physiotherapy ward. Based on the result bacterial concentration of indoor air of Gondar University teaching hospital was found between 480 and 1468 CFU/m(3). The result of one way ANOVA showed that the highest mean bacterial concentration (1271.00 CFU/m(3)) was found in Medical ward and the least (583.25 CFU/m(3)) concentration was found in ward D and the grand total average concentration was 878.43 CFU/m(3). Favorable conditions for growth and multiplication of bacteria like temperature (26.5-29.5 degrees C), humidity (64.5-85 %), presence of unhygienic attached toilets, poor waste management system and poor ventilation system were observed during the survey. Staphylococcus aureus was identified in 10 wards and Streptococcus pyogenes was isolated in 8 hospital wards. CONCLUSIONS: Compared with different indoor air biological standards, higher concentration of indoor air bacterial load was found in Gondar University teaching hospital. The higher bacterial load may be due to temperature, humidity, presence of unhygienic attached toilets, poor waste management system and poor ventilation system. Therefore, attention must be given to control those environmental factors which favor the growth and multiplication of microbes in indoor environment. In addition, also the ventilation condition, cleanliness of toilets, sweeping methods and waste disposal system of the compound should be improved. PMID- 27382464 TI - Most Italians attending a congress on health of elderly people do not know and do not recognize respiratory diseases. AB - BACKGROUND: The present study reports the results of a survey jointly carried out by three Italian respiratory scientific associations (AIMAR, AIPO, SIMeR) together with an important Federation of elderly patients (FederAnziani) during the National Conference of Italian Court for Health Right held in Rimini from November 29(th) to December 1(st), 2013. The survey, based on a spirometric examination preceded by a questionnaire on respiratory health, was conducted on elderly people coming from all Italian regions to attend the Conference. METHODS: Nine hundred forty-nine subjects (574 females and 375 males), mean age 66.2 +/- 10.1 years, were interviewed and performed spirometric examination. There were 137 smokers (14.4 %). Mean value of Body Mass Index (BMI) was significantly higher in males (27.6 +/- 6.6) than in females (26.3 +/- 4.3). RESULTS: 17.1 % (N = 143) of the studied subjects reported to be suffering from respiratory disease and the prevalent illnesses were asthma (31.5 %) and COPD/emphysema (24.5 %), but only 3.3 % of the whole surveyed group was able to identify COPD as a pulmonary disease, however without knowing its characteristics, while these were known by 0.5 % of the interviewed subjects only. A high number of subjects, 22 % of whom were smokers, declared chronic sputum production. 10.2 % of the study group showed an obstructive defect at spirometry when the criterium of lower limit of the normal (LLN) was considered, whereas it was 12.4 % if the fixed limit of 0.70 was chosen. 64 % of the obstructed people thought they did not have any respiratory disease. CONCLUSIONS: The results of this survey, able to spread the knowledge of respiratory diseases and spirometry in a wide sample of subjects for the most part scarcely aware of them, emphasize the need for a greater divulgation of respiratory issues among the general population. PMID- 27382465 TI - Phenotypic variation in metabolism and morphology correlating with animal swimming activity in the wild: relevance for the OCLTT (oxygen- and capacity limitation of thermal tolerance), allocation and performance models. AB - Ongoing climate change is affecting animal physiology in many parts of the world. Using metabolism, the oxygen- and capacity-limitation of thermal tolerance (OCLTT) hypothesis provides a tool to predict the responses of ectothermic animals to variation in temperature, oxygen availability and pH in the aquatic environment. The hypothesis remains controversial, however, and has been questioned in several studies. A positive relationship between aerobic metabolic scope and animal activity would be consistent with the OCLTT but has rarely been tested. Moreover, the performance model and the allocation model predict positive and negative relationships, respectively, between standard metabolic rate and activity. Finally, animal activity could be affected by individual morphology because of covariation with cost of transport. Therefore, we hypothesized that individual variation in activity is correlated with variation in metabolism and morphology. To test this prediction, we captured 23 wild European perch (Perca fluviatilis) in a lake, tagged them with telemetry transmitters, measured standard and maximal metabolic rates, aerobic metabolic scope and fineness ratio and returned the fish to the lake to quantify individual in situ activity levels. Metabolic rates were measured using intermittent flow respirometry, whereas the activity assay involved high-resolution telemetry providing positions every 30 s over 12 days. We found no correlation between individual metabolic traits and activity, whereas individual fineness ratio correlated with activity. Independent of body length, and consistent with physics theory, slender fish maintained faster mean and maximal swimming speeds, but this variation did not result in a larger area (in square metres) explored per 24 h. Testing assumptions and predictions of recent conceptual models, our study indicates that individual metabolism is not a strong determinant of animal activity, in contrast to individual morphology, which is correlated with in situ activity patterns. PMID- 27382466 TI - Success stories and emerging themes in conservation physiology. AB - The potential benefits of physiology for conservation are well established and include greater specificity of management techniques, determination of cause effect relationships, increased sensitivity of health and disturbance monitoring and greater capacity for predicting future change. While descriptions of the specific avenues in which conservation and physiology can be integrated are readily available and important to the continuing expansion of the discipline of 'conservation physiology', to date there has been no assessment of how the field has specifically contributed to conservation success. However, the goal of conservation physiology is to foster conservation solutions and it is therefore important to assess whether physiological approaches contribute to downstream conservation outcomes and management decisions. Here, we present eight areas of conservation concern, ranging from chemical contamination to invasive species to ecotourism, where physiological approaches have led to beneficial changes in human behaviour, management or policy. We also discuss the shared characteristics of these successes, identifying emerging themes in the discipline. Specifically, we conclude that conservation physiology: (i) goes beyond documenting change to provide solutions; (ii) offers a diversity of physiological metrics beyond glucocorticoids (stress hormones); (iii) includes approaches that are transferable among species, locations and times; (iv) simultaneously allows for human use and benefits to wildlife; and (v) is characterized by successes that can be difficult to find in the primary literature. Overall, we submit that the field of conservation physiology has a strong foundation of achievements characterized by a diversity of conservation issues, taxa, physiological traits, ecosystem types and spatial scales. We hope that these concrete successes will encourage the continued evolution and use of physiological tools within conservation-based research and management plans. PMID- 27382467 TI - Fisheries conservation on the high seas: linking conservation physiology and fisheries ecology for the management of large pelagic fishes. AB - Populations of tunas, billfishes and pelagic sharks are fished at or over capacity in many regions of the world. They are captured by directed commercial and recreational fisheries (the latter of which often promote catch and release) or as incidental catch or bycatch in commercial fisheries. Population assessments of pelagic fishes typically incorporate catch-per-unit-effort time-series data from commercial and recreational fisheries; however, there have been notable changes in target species, areas fished and depth-specific gear deployments over the years that may have affected catchability. Some regional fisheries management organizations take into account the effects of time- and area-specific changes in the behaviours of fish and fishers, as well as fishing gear, to standardize catch per-unit-effort indices and refine population estimates. However, estimates of changes in stock size over time may be very sensitive to underlying assumptions of the effects of oceanographic conditions and prey distribution on the horizontal and vertical movement patterns and distribution of pelagic fishes. Effective management and successful conservation of pelagic fishes requires a mechanistic understanding of their physiological and behavioural responses to environmental variability, potential for interaction with commercial and recreational fishing gear, and the capture process. The interdisciplinary field of conservation physiology can provide insights into pelagic fish demography and ecology (including environmental relationships and interspecific interactions) by uniting the complementary expertise and skills of fish physiologists and fisheries scientists. The iterative testing by one discipline of hypotheses generated by the other can span the fundamental-applied science continuum, leading to the development of robust insights supporting informed management. The resulting species-specific understanding of physiological abilities and tolerances can help to improve stock assessments, develop effective bycatch reduction strategies, predict rates of post-release mortality, and forecast the population effects of environmental change. In this synthesis, we review several examples of these interdisciplinary collaborations that currently benefit pelagic fisheries management. PMID- 27382468 TI - Intraspecific individual variation of temperature tolerance associated with oxygen demand in the European sea bass (Dicentrarchus labrax). AB - The European sea bass (Dicentrarchus labrax) is an economically important fish native to the Mediterranean and Northern Atlantic. Its complex life cycle involves many migrations through temperature gradients that affect the energetic demands of swimming. Previous studies have shown large intraspecific variation in swimming performance and temperature tolerance, which could include deleterious and advantageous traits under the evolutionary pressure of climate change. However, little is known of the underlying determinants of this individual variation. We investigated individual variation in temperature tolerance in 30 sea bass by exposing them to a warm temperature challenge test. The eight most temperature-tolerant and eight most temperature-sensitive fish were then studied further to determine maximal swimming speed (U CAT), aerobic scope and post exercise oxygen consumption. Finally, ventricular contractility in each group was determined using isometric muscle preparations. The temperature-tolerant fish showed lower resting oxygen consumption rates, possessed larger hearts and initially recovered from exhaustive exercise faster than the temperature sensitive fish. Thus, whole-animal temperature tolerance was associated with important performance traits. However, the temperature-tolerant fish also demonstrated poorer maximal swimming capacity (i.e. lower U CAT) than their temperature-sensitive counterparts, which may indicate a trade-off between temperature tolerance and swimming performance. Interestingly, the larger relative ventricular mass of the temperature-tolerant fish did not equate to greater ventricular contractility, suggesting that larger stroke volumes, rather than greater contractile strength, may be associated with thermal tolerance in this species. PMID- 27382469 TI - Evaluating the effect of sample type on American alligator (Alligator mississippiensis) analyte values in a point-of-care blood analyser. AB - The assessment of wildlife health has been enhanced by the ability of point-of care (POC) blood analysers to provide biochemical analyses of non-domesticated animals in the field. However, environmental limitations (e.g. temperature, atmospheric humidity and rain) and lack of reference values may inhibit researchers from using such a device with certain wildlife species. Evaluating the use of alternative sample types, such as plasma, in a POC device may afford researchers the opportunity to delay sample analysis and the ability to use banked samples. In this study, we examined fresh whole blood, fresh plasma and frozen plasma (sample type) pH, partial pressure of carbon dioxide (PCO2), bicarbonate (HCO3 (-)), total carbon dioxide (TCO2), base excess (BE), partial pressure of oxygen (PO2), oxygen saturation (sO2) and lactate concentrations in 23 juvenile American alligators (Alligator mississippiensis) using an i-STAT CG4+ cartridge. Our results indicate that sample type had no effect on lactate concentration values (F 2,65 = 0.37, P = 0.963), suggesting that the i-STAT analyser can be used reliably to quantify lactate concentrations in fresh and frozen plasma samples. In contrast, the other seven blood parameters measured by the CG4+ cartridge were significantly affected by sample type. Lastly, we were able to collect blood samples from all alligators within 2 min of capture to establish preliminary reference ranges for juvenile alligators based on values obtained using fresh whole blood. PMID- 27382470 TI - Context dependency of trait repeatability and its relevance for management and conservation of fish populations. AB - Repeatability of behavioural and physiological traits is increasingly a focus for animal researchers, for which fish have become important models. Almost all of this work has been done in the context of evolutionary ecology, with few explicit attempts to apply repeatability and context dependency of trait variation toward understanding conservation-related issues. Here, we review work examining the degree to which repeatability of traits (such as boldness, swimming performance, metabolic rate and stress responsiveness) is context dependent. We review methods for quantifying repeatability (distinguishing between within-context and across context repeatability) and confounding factors that may be especially problematic when attempting to measure repeatability in wild fish. Environmental factors such temperature, food availability, oxygen availability, hypercapnia, flow regime and pollutants all appear to alter trait repeatability in fishes. This suggests that anthropogenic environmental change could alter evolutionary trajectories by changing which individuals achieve the greatest fitness in a given set of conditions. Gaining a greater understanding of these effects will be crucial for our ability to forecast the effects of gradual environmental change, such as climate change and ocean acidification, the study of which is currently limited by our ability to examine trait changes over relatively short time scales. Also discussed are situations in which recent advances in technologies associated with electronic tags (biotelemetry and biologging) and respirometry will help to facilitate increased quantification of repeatability for physiological and integrative traits, which so far lag behind measures of repeatability of behavioural traits. PMID- 27382471 TI - Methods matter: considering locomotory mode and respirometry technique when estimating metabolic rates of fishes. AB - Respirometry is frequently used to estimate metabolic rates and examine organismal responses to environmental change. Although a range of methodologies exists, it remains unclear whether differences in chamber design and exercise (type and duration) produce comparable results within individuals and whether the most appropriate method differs across taxa. We used a repeated-measures design to compare estimates of maximal and standard metabolic rates (MMR and SMR) in four coral reef fish species using the following three methods: (i) prolonged swimming in a traditional swimming respirometer; (ii) short-duration exhaustive chase with air exposure followed by resting respirometry; and (iii) short duration exhaustive swimming in a circular chamber. We chose species that are steady/prolonged swimmers, using either a body-caudal fin or a median-paired fin swimming mode during routine swimming. Individual MMR estimates differed significantly depending on the method used. Swimming respirometry consistently provided the best (i.e. highest) estimate of MMR in all four species irrespective of swimming mode. Both short-duration protocols (exhaustive chase and swimming in a circular chamber) produced similar MMR estimates, which were up to 38% lower than those obtained during prolonged swimming. Furthermore, underestimates were not consistent across swimming modes or species, indicating that a general correction factor cannot be used. However, SMR estimates (upon recovery from both of the exhausting swimming methods) were consistent across both short-duration methods. Given the increasing use of metabolic data to assess organismal responses to environmental stressors, we recommend carefully considering respirometry protocols before experimentation. Specifically, results should not readily be compared across methods; discrepancies could result in misinterpretation of MMR and aerobic scope. PMID- 27382473 TI - Reduced salinity tolerance in the Arctic grayling (Thymallus arcticus) is associated with rapid development of a gill interlamellar cell mass: implications of high-saline spills on native freshwater salmonids. AB - Arctic grayling (Thymallus arcticus) are salmonids that have a strict freshwater existence in post-glacial North America. Oil and gas development is associated with production of high volumes of hypersaline water. With planned industrial expansion into northern areas of Canada and the USA that directly overlap grayling habitat, the threat of accidental saline water release poses a significant risk. Despite this, we understand little about the responses of grayling to hypersaline waters. We compared the physiological responses and survivability of Arctic grayling and rainbow trout (Oncorhynchus mykiss) to tolerate an acute transfer to higher saline waters. Arctic grayling and rainbow trout were placed directly into 17 ppt salinity and sampled at 24 and 96 h along with control animals in freshwater at 24 h. Serum sodium, chloride and osmolality levels increased significantly in grayling at both 24 and 96 h time points, whereas trout were able to compensate for the osmoregulatory disturbance by 96 h. Sodium-potassium ATPase mRNA expression responses to salinity were also compared, demonstrating the inability of the grayling to up-regulate the seawater isoform nkaalpha1b. Our results demonstrated a substantially lower salinity tolerance in grayling. We also found a significant salinity-induced morphological gill remodelling by Arctic grayling, as demonstrated by the rapid growth of an interlamellar cell mass by 24 h that persisted at 96 h. We visualized and quantified the appearance of the interlamellar cell mass as a response to high salinity, although the functional significance remains to be understood fully. Compared with rainbow trout, which are used as an environmental regulatory species, Arctic grayling are unable to compensate for the osmotic stressors that would result from a highly saline produced water spill. Given these new data, collaboration between fisheries and the oil and gas industry will be vital in the long-term conservation strategies with regard to the Arctic grayling in their native habitat. PMID- 27382474 TI - Feather and faecal corticosterone concentrations predict future reproductive decisions in harlequin ducks (Histrionicus histrionicus). AB - Understanding sources of reproductive variation can inform management and conservation decisions, population ecology and life-history theory. Annual reproductive variation can drive population growth rate and can be influenced by factors from across the annual cycle (known as carry-over effects). The majority of studies, however, focus solely on the role of current environmental events. Past events often influence future reproductive decisions and success but can be logistically difficult to collect and quantify, especially in migratory species. Recent work indicates that glucocorticoids may prove good indicators to evaluate carry-over effects across life-history transitions. Here, we evaluated three different measures of glucocorticoid physiology (feathers, faeces and plasma) to evaluate the predictability of future breeding decision in the harlequin duck (Histrionicus histrionicus). We collected tail and back feathers, plasma and faeces for glucocorticoid analysis, and fitted female harlequin ducks with very high-frequency transmitters to track their breeding decisions. Both back feathers (moulted immediately before the current season) and faecal glucocorticoid metabolites were identified as important predictive factors of reproductive decisions; high concentrations of glucocorticoid metabolites in back feathers and faeces predicted a higher likelihood of reproductive deferral for the year. Although back and tail feather corticosterone concentrations were correlated, tail feathers (moulted at the end of the previous breeding season) did not predict breeding decisions. Plasma corticosterone concentrations were collected over too broad a time range after capture to be useful in this study. This study demonstrates the utility of non-invasive corticosterone metrics in predicting breeding decisions and supports the use of feathers to measure carry-over effects in migratory birds. With this technique, we identified the prenuptial moult as an important life-history phase that contributes to reproductive decisions. Identification of critical life-history phases is paramount to efficient management of species. PMID- 27382472 TI - Are global warming and ocean acidification conspiring against marine ectotherms? A meta-analysis of the respiratory effects of elevated temperature, high CO2 and their interaction. AB - With the occurrence of global change, research aimed at estimating the performance of marine ectotherms in a warmer and acidified future has intensified. The concept of oxygen- and capacity-limited thermal tolerance, which is inspired by the Fry paradigm of a bell-shaped increase-optimum-decrease-type response of aerobic scope to increasing temperature, but also includes proposed negative and synergistic effects of elevated CO2 levels, has been suggested as a unifying framework. The objectives of this meta-analysis were to assess the following: (i) the generality of a bell-shaped relationship between absolute aerobic scope (AAS) and temperature; (ii) to what extent elevated CO2 affects resting oxygen uptake MO2rest and AAS; and (iii) whether there is an interaction between elevated temperature and CO2. The behavioural effects of CO2 are also briefly discussed. In 31 out of 73 data sets (both acutely exposed and acclimated), AAS increased and remained above 90% of the maximum, whereas a clear thermal optimum was observed in the remaining 42 data sets. Carbon dioxide caused a significant rise in MO2rest in only 18 out of 125 data sets, and a decrease in 25, whereas it caused a decrease in AAS in four out of 18 data sets and an increase in two. The analysis did not reveal clear evidence for an overall correlation with temperature, CO2 regime or duration of CO2 treatment. When CO2 had an effect, additive rather than synergistic interactions with temperature were most common and, interestingly, they even interacted antagonistically on MO2rest and AAS. The behavioural effects of CO2 could complicate experimental determination of respiratory performance. Overall, this meta-analysis reveals heterogeneity in the responses to elevated temperature and CO2 that is not in accordance with the idea of a single unifying principle and which cannot be ignored in attempts to model and predict the impacts of global warming and ocean acidification on marine ectotherms. PMID- 27382475 TI - Contribution of Arab countries to pharmaceutical wastewater literature: a bibliometric and comparative analysis of research output. AB - BACKGROUND: Recently, the pharmaceutical manufacturing industry has been growing rapidly in many countries in the world, including in Arab countries. Pharmaceuticals reach aquatic environments and are prevalent at small concentrations in wastewater from the drug manufacturing industry and hospitals. Such presence also occurs in domestic wastewater and results from the disposal of unused and expired medicines. Therefore, the objective of this study was to analyze and compare the quantity and quality of publications made by researchers in Arab countries on pharmaceutical wastewater. METHODS: To retrieve documents related to pharmaceutical wastewater, we used the Scopus database on November 21, 2015. All documents with terms related to pharmaceutical wastewater in the title or abstract were analysed. Results obtained from Arab countries were compared with those obtained from Turkey, Iran and Israel. RESULTS: Globally, a total of 6360 publications were retrieved while those from Arab countries, Iran, Turkey and Israel, were 179, 113, 96 and 54 publications respectively. The highest share of publications belonged to Kingdom of Saudi Arabia (KSA) with a total of 47 (26.2 %) publications, followed by Egypt (38; 21.2 %), Tunisia (17; 9.5 %) and Morocco (16; 8.9 %). The total number of citations was 1635, with a mean of 9.13 and a median (inter quartile range) of 3 (1.0-10.0). The study identified 87 (48.6 %) documents with 32 countries of international collaboration with Arab countries. It was noted that Arab researchers collaborated mainly with authors in Western Europe (54; 30.2 %), followed by authors from the Asiatic region (29; 16.2 %) and Northern America (15; 8.4 %). The most productive institution was King Saud University, KSA (13; 7.3 %), followed by the National Research Centre, Egypt (10; 7.3 %). CONCLUSIONS: This study showed that KSA has the largest share of productivity on pharmaceutical wastewater research. Bibliometric analysis demonstrated that research productivity, mainly from Arab countries in pharmaceutical wastewater research, was relatively lagging behind. More research effort is required for Arab countries to catch up with those of non-Arab Middle Easter countries on pharmaceutical wastewater research. PMID- 27382476 TI - Acute respiratory symptoms and evacuation-related behavior after exposure to chlorine gas leakage. AB - BACKGROUND: A study was performed on the accidental chlorine gas leakage that occurred in a factory of printed circuit boards manufactured without chlorine. Health examination was performed for all 52 workers suspected of exposure to chlorine gas, and their evacuation-related behaviors were observed in addition to analyzing the factors that affected the duration of their acute respiratory symptoms. METHODS: Behavioral characteristics during the incidence of the accidental chlorine gas leakage, the estimated time of exposure, and the duration of subjective acute respiratory symptoms were investigated. In addition, clinical examination, chest radiography, and dental erosion test were performed. As variables that affected the duration of respiratory symptoms, dose group, body weight, age, sex, smoking, work period, and wearing a protective gear were included and analyzed by using the Cox proportional hazard model. RESULTS: Of 47 workers exposed to chlorine gas, 36 (77 %) developed more than one subjective symptom. The duration of the subjective symptoms according to exposure level significantly differed, with a median of 1 day (range, 0-5 days) in the low exposure group and 2 days (range, 0-25 days) in the high-exposure group. Among the variables that affected the duration of the acute respiratory symptoms, which were analyzed by using the Cox proportional hazard model, only exposure level was significant (hazard ratio 2.087, 95 % CI = 1.119, 3.890). Regarding the evacuation-related behaviors, 22 workers (47 %) voluntarily evacuated to a safety zone immediately after recognizing the accidental exposure, but 25 workers (43 %) delayed evacuation until the start of mandatory evacuation (min 5, max 25 min). CONCLUSIONS: The duration of the subjective acute respiratory symptoms significantly differed between the low- and high-exposure groups. Among the 27 workers in the high-exposure group, 17 misjudged the toxicity after being aware of the gas leakage, which is a relatively high number. PMID- 27382477 TI - Virtual electrode design for increasing spatial resolution in retinal prosthesis. AB - Retinal prostheses systems are currently used to restore partial vision to patients blinded by degenerative diseases by electrically stimulating surviving retinal cells. To obtain likely maximum resolution, electrode size is minimised, allowing for a large quantity on an array and localised stimulation regions. Besides the small size leading to fabrication difficulties and higher electrochemical charge density, there are challenges associated with the number of drivers needed for a large electrode count as well as the strategies to deliver sufficient power to these drivers wirelessly. In hopes to increase electrode resolution while avoiding these issues, the authors propose a new 'virtual electrode' design to increase locations of likely stimulation. Passive metallisation strategically placed between disk electrodes, combined with alternating surrounding stimuli, channel current into a location between electrodes, producing a virtual stimulation site. A computational study was conducted to optimise the passive metal element geometry, quantify the expected current density output, and simulate retinal ganglion cell activity due to virtual electrode stimulation. Results show that this procedure leads to array geometry that focuses injected current and achieves retinal ganglion cell stimulation in a region beneath the 'virtual electrode,' creating an alternate stimulation site without additional drivers. PMID- 27382478 TI - Computationally efficient real-time interpolation algorithm for non-uniform sampled biosignals. AB - This Letter presents a novel, computationally efficient interpolation method that has been optimised for use in electrocardiogram baseline drift removal. In the authors' previous Letter three isoelectric baseline points per heartbeat are detected, and here utilised as interpolation points. As an extension from linear interpolation, their algorithm segments the interpolation interval and utilises different piecewise linear equations. Thus, the algorithm produces a linear curvature that is computationally efficient while interpolating non-uniform samples. The proposed algorithm is tested using sinusoids with different fundamental frequencies from 0.05 to 0.7 Hz and also validated with real baseline wander data acquired from the Massachusetts Institute of Technology University and Boston's Beth Israel Hospital (MIT-BIH) Noise Stress Database. The synthetic data results show an root mean square (RMS) error of 0.9 MUV (mean), 0.63 MUV (median) and 0.6 MUV (standard deviation) per heartbeat on a 1 mVp-p 0.1 Hz sinusoid. On real data, they obtain an RMS error of 10.9 MUV (mean), 8.5 MUV (median) and 9.0 MUV (standard deviation) per heartbeat. Cubic spline interpolation and linear interpolation on the other hand shows 10.7 MUV, 11.6 MUV (mean), 7.8 MUV, 8.9 MUV (median) and 9.8 MUV, 9.3 MUV (standard deviation) per heartbeat. PMID- 27382479 TI - Modular continuous wavelet processing of biosignals: extracting heart rate and oxygen saturation from a video signal. AB - A novel method of extracting heart rate and oxygen saturation from a video-based biosignal is described. The method comprises a novel modular continuous wavelet transform approach which includes: performing the transform, undertaking running wavelet archetyping to enhance the pulse information, extraction of the pulse ridge time-frequency information [and thus a heart rate (HRvid) signal], creation of a wavelet ratio surface, projection of the pulse ridge onto the ratio surface to determine the ratio of ratios from which a saturation trending signal is derived, and calibrating this signal to provide an absolute saturation signal (SvidO2). The method is illustrated through its application to a video photoplethysmogram acquired during a porcine model of acute desaturation. The modular continuous wavelet transform-based approach is advocated by the author as a powerful methodology to deal with noisy, non-stationary biosignals in general. PMID- 27382480 TI - Robust cardiac event change detection method for long-term healthcare monitoring applications. AB - A long-term continuous cardiac health monitoring system highly demands more battery power for real-time transmission of electrocardiogram (ECG) signals and increases bandwidth, treatment costs and traffic load of the diagnostic server. In this Letter, the authors present an automated low-complexity robust cardiac event change detection (CECD) method that can continuously detect specific changes in PQRST morphological patterns and heart rhythms and then enable transmission/storing of the recorded ECG signals. The proposed CECD method consists of four stages: ECG signal quality assessment, R-peak detection and beat waveform extraction, temporal and RR interval feature extraction and cardiac event change decision. The proposed method is tested and validated using both normal and abnormal ECG signals including different types of arrhythmia beats, heart rates and signal quality. Results show that the method achieves an average sensitivity of 99.76%, positive predictivity of 94.58% and overall accuracy of 94.32% in determining the changes in heartbeat waveforms of the ECG signals. PMID- 27382481 TI - Process techniques for human thoracic electrical bio-impedance signal in remote healthcare systems. AB - Analysis of thoracic electrical bio-impedance (TEB) facilitates heart stroke volume in sudden cardiac arrest. This Letter proposes several efficient and computationally simplified adaptive algorithms to display high-resolution TEB component. In a clinical environment, TEB signal encounters with various physiological and non-physiological phenomenon, which masks the tiny features that are important in identifying the intensity of the stroke. Moreover, computational complexity is an important parameter in a modern wearable healthcare monitoring tool. Hence, in this Letter, the authors propose a new signal conditioning technique for TEB enhancement in remote healthcare systems. For this, the authors have chosen higher order adaptive filter as a basic element in the process of TEB. To improve filtering capability, convergence speed, to reduce computational complexity of the signal conditioning technique, the authors apply data normalisation and clipping the data regressor. The proposed implementations are tested on real TEB signals. Finally, simulation results confirm that proposed regressor clipped normalised higher order filter is suitable for a practical healthcare system. PMID- 27382482 TI - Path loss variation of on-body UWB channel in the frequency bands of IEEE 802.15.6 standard. AB - The wireless body area network (WBAN) has gaining tremendous attention among researchers and academicians for its envisioned applications in healthcare service. Ultra wideband (UWB) radio technology is considered as excellent air interface for communication among body area network devices. Characterisation and modelling of channel parameters are utmost prerequisite for the development of reliable communication system. The path loss of on-body UWB channel for each frequency band defined in IEEE 802.15.6 standard is experimentally determined. The parameters of path loss model are statistically determined by analysing measurement data. Both the line-of-sight and non-line-of-sight channel conditions are considered in the measurement. Variations of parameter values with the size of human body are analysed along with the variation of parameter values with the surrounding environments. It is observed that the parameters of the path loss model vary with the frequency band as well as with the body size and surrounding environment. The derived parameter values are specific to the particular frequency bands of IEEE 802.15.6 standard, which will be useful for the development of efficient UWB WBAN system. PMID- 27382483 TI - Heart rate variability estimation in photoplethysmography signals using Bayesian learning approach. AB - Heart rate variability (HRV) has become a marker for various health and disease conditions. Photoplethysmography (PPG) sensors integrated in wearable devices such as smart watches and phones are widely used to measure heart activities. HRV requires accurate estimation of time interval between consecutive peaks in the PPG signal. However, PPG signal is very sensitive to motion artefact which may lead to poor HRV estimation if false peaks are detected. In this Letter, the authors propose a probabilistic approach based on Bayesian learning to better estimate HRV from PPG signal recorded by wearable devices and enhance the performance of the automatic multi scale-based peak detection (AMPD) algorithm used for peak detection. The authors' experiments show that their approach enhances the performance of the AMPD algorithm in terms of number of HRV related metrics such as sensitivity, positive predictive value, and average temporal resolution. PMID- 27382484 TI - Development of a clinical decision support system using genetic algorithms and Bayesian classification for improving the personalised management of women attending a colposcopy room. AB - Cervical cancer (CxCa) is often the result of underestimated abnormalities in the test Papanicolaou (Pap test). The recent advances in the study of the human papillomavirus (HPV) infection (the necessary cause for CxCa development) have guided clinical practice to add HPV related tests alongside the Pap test. In this way, today, HPV DNA testing is well accepted as an ancillary test and it is used for the triage of women with abnormal findings in cytology. However, these tests are either highly sensitive or highly specific, and therefore none of them provides an optimal solution. In this Letter, a clinical decision support system based on a hybrid genetic algorithm - Bayesian classification framework is presented, which combines the results of the Pap test with those of the HPV DNA test in order to exploit the benefits of each method and produce more accurate outcomes. Compared with the medical tests and their combinations (co-testing), the proposed system produced the best receiver operating characteristic curve and the most balanced combination among sensitivity and specificity in detecting high grade cervical intraepithelial neoplasia and CxCa (CIN2+). This system may support decision-making for the improved management of women who attend a colposcopy room following a positive test result. PMID- 27382485 TI - Identification of the First De Novo UBIAD1 Gene Mutation Associated with Schnyder Corneal Dystrophy. AB - Purpose. To report the identification of the first de novo UBIAD1 missense mutation in an individual with Schnyder corneal dystrophy (SCD). Methods. A slit lamp examination was performed on a 47-year-old woman without a family history of corneal disorders. The proband's parents, two sisters, and son were also examined and genomic DNA from all six individuals was collected. The exons and exon-intron boundaries of UBIAD1 were screened using Sanger sequencing. Identified mutations were screened for in 200 control chromosomes. In silico analysis predicted the impact of identified mutations on protein function and structure. Results. Slit lamp examination of the proband revealed findings consistent with SCD. Corneas of the family members appeared unaffected. Screening of UBIAD1 in the proband identified a novel heterozygous c.308C>T mutation, predicted to encode the missense amino acid substitution p.(Thr103Ile). This mutation was not identified in any of the family members or in 200 control chromosomes and was predicted to be damaging to normal protein function and structure. Conclusions. We present a novel heterozygous de novo missense mutation in UBIAD1, p.(Thr103Ile), identified in a patient with classic clinical features of SCD. This highlights the value of genetic testing in clinical diagnostic settings, even in the absence of a positive family history. PMID- 27382486 TI - Keratorefractive Effect of High Intensity Focused Ultrasound Keratoplasty on Rabbit Eyes. AB - Purpose. To evaluate high intensity focused ultrasound (HIFU) as an innovation and noninvasive technique to correct presbyopia by altering corneal curvature in the rabbit eye. Methods. Eighteen enucleated rabbit eyes were treated with a prototype HIFU keratoplasty. According to the therapy power, these eyes were divided three groups: group 1 (1 W), group 2 (2 W), and group 3 (3 W). The change in corneal power was quantified by a Sirius Scheimpflug camera. Light microscopy (LM) and transmission electron microscopy (TEM) were performed to determine the effect on the corneal stroma. Results. In the treated eyes, the corneal curvature increases from 49.42 +/- 0.30 diopters (D) and 48.00 +/- 1.95 D before procedure to 51.37 +/- 1.11 D and 57.00 +/- 1.84 D after HIFU keratoplasty application in groups 1 and 3, respectively. The major axis and minor axis of the focal region got longer when the powers of the HIFU got increased; the difference was statistically significant (p < 0.05). LM and TEM showed HIFU-induced shrinkage of corneal stromal collagen with little disturbance to the underlying epithelium. Conclusions. We have preliminarily exploited HIFU to establish a new technique for correcting presbyopia. HIFU keratoplasty will be a good application prospect for treating presbyopia. PMID- 27382487 TI - A Prospective Study of the Incidence of Retinopathy of Prematurity in China: Evaluation of Different Screening Criteria. AB - To investigate the incidence of Retinopathy of Prematurity (ROP) in Beijing, North China, and to evaluate the effectiveness of different ROP screening criteria, we conducted a prospective cohort study in a single-neonatal intensive care unit (NICU). A total of 2997 premature infants with birth weight (BW) <= 2000 g and/or gestational age (GA) <= 34 weeks had completed ROP screening. ROP was diagnosed in 356 (11.9%) infants. The mean GA was 30.46 +/- 1.98 weeks and the mean BW was 1477.35 +/- 371.29 g. Of the 59 (2.0%) infants receiving treatment, the mean GA was 29.37 +/- 2.10 weeks, and the mean BW was 1240.80 +/- 330.71 g. The incidence of ROP declined from 14.7% in 2009 and 11.1% in 2010 to 9.5% in 2011. The United Kingdom (UK) criteria could reduce the screening number by 40.8%, and 3 infants with type I ROP needing treatment were missed, but none in 2011. The United States (US) criteria could reduce the screening number by 66.5%, and 10 infants with type I ROP needing treatment were missed, including one in 2011. So the UK criteria may be appropriate for screening of ROP in our NICU in 2011. Future multisite epidemiologic studies are required to establish suitable ROP screening criteria in China. PMID- 27382488 TI - Using Soluble Transferrin Receptor and Taking Inflammation into Account When Defining Serum Ferritin Cutoffs Improved the Diagnosis of Iron Deficiency in a Group of Canadian Preschool Inuit Children from Nunavik. AB - The prevalence of iron depletion, iron deficient erythropoiesis (IDE), and iron deficiency anemia (IDA) was assessed in preschool Inuit children using soluble transferrin receptor (sTfR) and traditional indicators of iron status while disregarding or taking inflammation into account when defining SF cutoffs. Iron depletion was defined as follows: (1) SF < 15 MUg/L regardless of the C-reactive protein (CRP) level and (2) SF < 15 or <50 MUg/L with CRP <= 5 or >5 mg/L, respectively. IDE corresponded to iron depletion combined with total iron binding capacity > 72 MUmol/L and/or transferrin saturation < 16%. Iron depletion and IDE affected almost half of the children when accounting for inflammation, compared to one-third when the SF cutoff was defined regardless of CRP level (P < 0.0001). The prevalence of IDE adjusted for inflammation (45.1%) was very similar to the prevalence observed when sTfR was used as a sole marker of IDE (47.4%). The prevalence of anemia was 15%. The prevalence of IDA (IDE + hemoglobin < 110 g/L) was higher when accounting for than when disregarding inflammation (8.0% versus 6.2%, P = 0.083). Using sTfR and different SF cutoffs for children with versus without inflammation improved the diagnosis of iron depletion and IDE. Our results confirm that Inuit children are at particularly high risk for iron deficiency. PMID- 27382489 TI - The Incidence of Euphoria in Multiple Sclerosis: Artefact of Measure. AB - Background. A subgroup of MS patients present with "euphoria." Classical authors describe this symptom as the predominant mood state of these patients, while contemporary authors regard it as rare. Objective. This study aimed to address these discrepancies and investigate the contributions made by varying operational definitions and measurement instruments. Methods. One hundred MS patients and 100 matched controls completed the classical interview of Cottrell and Wilson and the modern Neuropsychiatric Inventory in a once-off interview. Results. The MS group demonstrated high frequencies of euphoria using the classical measure but low frequencies using the contemporary measure and definition. The matched control group demonstrated significantly higher rates than the MS group using the classical measure and lower rates than the MS group using the contemporary measure. Conclusion. The discrepancies in incidence rates of euphoria noted in the literature do not reflect a change in the incidence of euphoria in MS, but rather in the definition and operationalisation of "euphoria." Furthermore, these results highlight the importance of characterising what represents pathological euphoria as well as the need for better definitions and instruments of measure. PMID- 27382492 TI - The Histopathological Spectrum of Pyogenic Granuloma: A Case Series. AB - Background. Pyogenic granuloma is a reactive tumor-like lesion commonly affecting the oral cavity. These lesions usually appear as localized solitary nodule with a sessile or pedunculated base and colour varying from red, purplish, or pink, depending on the vascularity of the lesion. Pyogenic granuloma shows predilection for gingiva and is usually slow growing, but at times it shows rapid growth. The natural course of this lesion can be categorized into three distinct phases, namely, (i) cellular phase, (ii) capillary phase/vascular phase, and (iii) involutionary phase. Histopathologically, pyogenic granuloma is classified into lobular capillary hemangioma (LCH) and non-lobular capillary hemangioma (non LCH). Case Presentation. In this series, four cases (varied age groups and both genders) of pyogenic granuloma showing varying histopathological presentation in relation to its clinical course have been described. The lesion in its early phase reveals diffuse endothelial cells, with few budding into capillaries. Among the capillary phase, the LCH type shows numerous blood vessels organized into lobular aggregates whereas the non-LCH type does not show any such organization and resembles granulation tissue. The involutionary phase shows healing of the lesion and is characterized by extensive fibrosis in the connective tissue. Conclusion. In conclusion, knowledge of the various histopathological presentation of this lesion is necessary for proper identification. PMID- 27382490 TI - Current Evidence for Developmental, Structural, and Functional Brain Defects following Prenatal Radiation Exposure. AB - Ionizing radiation is omnipresent. We are continuously exposed to natural (e.g., radon and cosmic) and man-made radiation sources, including those from industry but especially from the medical sector. The increasing use of medical radiation modalities, in particular those employing low-dose radiation such as CT scans, raises concerns regarding the effects of cumulative exposure doses and the inappropriate utilization of these imaging techniques. One of the major goals in the radioprotection field is to better understand the potential health risk posed to the unborn child after radiation exposure to the pregnant mother, of which the first convincing evidence came from epidemiological studies on in utero exposed atomic bomb survivors. In the following years, animal models have proven to be an essential tool to further characterize brain developmental defects and consequent functional deficits. However, the identification of a possible dose threshold is far from complete and a sound link between early defects and persistent anomalies has not yet been established. This review provides an overview of the current knowledge on brain developmental and persistent defects resulting from in utero radiation exposure and addresses the many questions that still remain to be answered. PMID- 27382494 TI - Haemophilus parainfluenzae Mural Endocarditis: Case Report and Review of the Literature. AB - Haemophilus parainfluenzae, which uncommonly causes endocarditis, has never been documented to cause mural involvement. A 62-year-old immunocompetent female without predisposing risk factors for endocarditis except for poor dentition presented with fever, emesis, and dysmetria. Echocardiography found a mass attached to the left ventricular wall with finger-like projections. Computed tomography showed evidence of embolic phenomena to the brain, kidneys, spleen, and colon. Cardiac MRI revealed involvement of the chordae tendineae of the anterior papillary muscles. Blood cultures grew Haemophilus parainfluenzae. The patient was treated successfully with ceftriaxone with resolution of symptoms, including neurologic deficits. After eleven days of antibiotics a worsening holosystolic murmur was discovered. Worsening mitral regurgitation on echocardiography was only found three weeks later. Nine weeks after presentation, intraoperative evaluation revealed chord rupture but no residual vegetation and mitral repair was performed. Four weeks after surgery, the patient was back to her baseline. This case illustrates the ability of Haemophilus parainfluenzae to form large mural vegetations with high propensity of embolization in otherwise normal cardiac tissue among patients with dental risk factors. It also underscores the importance of physical examination in establishing a diagnosis of endocarditis and monitoring for progression of disease. PMID- 27382491 TI - Regeneration of Zebrafish CNS: Adult Neurogenesis. AB - Regeneration in the animal kingdom is one of the most fascinating problems that have allowed scientists to address many issues of fundamental importance in basic biology. However, we came to know that the regenerative capability may vary across different species. Among vertebrates, fish and amphibians are capable of regenerating a variety of complex organs through epimorphosis. Zebrafish is an excellent animal model, which can repair several organs like damaged retina, severed spinal cord, injured brain and heart, and amputated fins. The focus of the present paper is on spinal cord regeneration in adult zebrafish. We intend to discuss our current understanding of the cellular and molecular mechanism(s) that allows formation of proliferating progenitors and controls neurogenesis, which involve changes in epigenetic and transcription programs. Unlike mammals, zebrafish retains radial glia, a nonneuronal cell type in their adult central nervous system. Injury induced proliferation involves radial glia which proliferate, transcribe embryonic genes, and can give rise to new neurons. Recent technological development of exquisite molecular tools in zebrafish, such as cell ablation, lineage analysis, and novel and substantial microarray, together with advancement in stem cell biology, allowed us to investigate how progenitor cells contribute to the generation of appropriate structures and various underlying mechanisms like reprogramming. PMID- 27382495 TI - Multifocal Head and Neck Neurofibromas with Osseous Abnormalities and Muscular Hypoplasia in a Child with Neurofibromatosis: Type I. AB - Neurofibromatosis type 1 (NF1) is a clinically and genetically distinct disease involving both neuroectodermal and mesenchymal derivatives. Orofacial manifestations in NF1 have been documented before but occurrence of multifocal intraosseous (IO) and extraosseous (EO) neurofibromas is rare. The present case highlights the importance of imaging findings in the diagnosis and management of multifocal jaw, infratemporal, and parotid neurofibromas with muscular hypoplasia in an eight-year-old girl with NF1. Apart from orthopantomograms (OPG), three dimensional computed tomography (3D CT) and cross-sectional reformations were valuable in delineating the extent of the lytic lesion and identifying additional bony deformities of the mandible. Magnetic resonance imaging (MRI) helped to identify the solid nature of the lesion and true extent of the soft tissue mass. PMID- 27382496 TI - Traumatic Cardiac Injury: Ventricular Perforation Caught on CT. AB - Myocardial rupture is a rare imaging diagnosis given its clinical severity and high mortality. Early findings should be promptly communicated to the trauma service to ensure immediate intervention. We present a rare case of blowout perforation of the right ventricle which was prospectively diagnosed on computed tomography (CT) leading to emergent operative repair. The patient subsequently survived and was discharged after a lengthy hospital course. PMID- 27382493 TI - Mutation in LEMD3 (Man1) Associated with Osteopoikilosis and Late-Onset Generalized Morphea: A New Buschke-Ollendorf Syndrome Variant. AB - Introduction. Buschke-Ollendorf syndrome (BOS) is an uncommon syndrome characterized by osteopoikilosis and other bone abnormalities, accompanied by skin lesions, most frequently connective tissue nevi. BOS is caused by mutations in the LEMD3 gene, which encodes the inner nuclear membrane protein Man1. We describe a unique case of osteopoikilosis associated with late-onset localized scleroderma and familial LEMD3 mutations. Case Report. A 72-year-old woman presented with adult-onset diffuse morphea and bullous skin lesions. Evaluation revealed multiple hyperostotic lesions (osteopoikilosis) suggestive of BOS. DNA sequencing identified a previously undescribed nonsense mutation (Trp621X) in the LEMD3 gene encoding Man1. Two additional family members were found to have osteopoikilosis and carry the same LEMD3 mutation. Conclusions and Relevance. We report a unique familial LEMD3 mutation in an individual with osteopoikilosis and late-onset morphea. We propose that this constellation represents a novel syndromic variant of BOS. PMID- 27382497 TI - An Autopsy Case of Fulminant Amebic Colitis in a Patient with a History of Rheumatoid Arthritis. AB - Generally, amebic colitis is localized around the mucosal membrane and often accompanied by diarrhea and abdominal pain. We describe a patient with a history of rheumatoid arthritis who had received prolonged steroid therapy. The patient complained of breathing difficulties because of rheumatoid lung disease. Although the patient was given antibacterial agent, the symptoms did not improve until death. We did an autopsy and found that he had fulminant amebic colitis, although the patient was not previously examined. Histochemical analysis revealed severe inflammation and full-thickness necrosis of the colon by ameba, suggesting the involvement of ameba in the progression of the overall condition. PMID- 27382498 TI - Anatomy Ontology Matching Using Markov Logic Networks. AB - The anatomy of model species is described in ontologies, which are used to standardize the annotations of experimental data, such as gene expression patterns. To compare such data between species, we need to establish relationships between ontologies describing different species. Ontology matching is a kind of solutions to find semantic correspondences between entities of different ontologies. Markov logic networks which unify probabilistic graphical model and first-order logic provide an excellent framework for ontology matching. We combine several different matching strategies through first-order logic formulas according to the structure of anatomy ontologies. Experiments on the adult mouse anatomy and the human anatomy have demonstrated the effectiveness of proposed approach in terms of the quality of result alignment. PMID- 27382499 TI - Understanding Genetic Diversity of Sorghum Using Quantitative Traits. AB - Sorghum is the important cereal crop around the world and hence understanding and utilizing the genetic variation in sorghum accessions are essential for improving the crop. A good understanding of genetic variability among the accessions will enable precision breeding. So profiling the genetic diversity of sorghum is imminent. In the present investigation, forty sorghum accessions consisting of sweet sorghum, grain sorghum, forage sorghum, mutant lines, maintainer lines, and restorer lines were screened for genetic diversity using quantitative traits. Observations were recorded on 14 quantitative traits, out of which 9 diverse traits contributing to maximum variability were selected for genetic diversity analysis. The principle component analysis revealed that the panicle width, stem girth, and leaf breadth contributed maximum towards divergence. By using hierarchical cluster analysis, the 40 accessions were grouped under 6 clusters. Cluster I contained maximum number of accessions and cluster VI contained the minimum. The maximum intercluster distance was observed between cluster VI and cluster IV. Cluster III had the highest mean value for hundred-seed weight and yield. Hence the selection of parents must be based on the wider intercluster distance and superior mean performance for yield and yield components. Thus in the present investigation quantitative data were able to reveal the existence of a wide genetic diversity among the sorghum accessions used providing scope for further genetic improvement. PMID- 27382500 TI - The Role Descriptions of Triage Nurse in Emergency Department: A Delphi Study. AB - Background. Triage nurses play a pivotal role in the emergency department. However some researchers have attempted to expand triage nurse's role; remarkable discrepancies exist among scholarly communities. The aim was to develop a role description of triage nurse relying on the experts. Methods. A modified Delphi study consisting of 3 rounds was performed from March to October 2014. In the first round, an extensive review of the literature was conducted. Expert selection was conducted through a purposeful sample of 38 emergency medicine experts. Results. Response rates for the second and third rounds were 37% and 58%. Average age of panelists was (38.42 +/- 5.94) years. Thirty-nine out of 54 items reached to the final round. Prioritizing had the higher agreement rate and least agreement on triage related interventions. Conclusion. Triage nursing as a relatively new role for nurses needs significant development to be practiced. Comprehensive educational programs and developmental research are required to support diagnostic and therapeutic interventions in triage practice by nurses. PMID- 27382501 TI - Patterns and Determinants of Treatment Seeking among Previously Untreated Psychotic Patients in Aceh Province, Indonesia: A Qualitative Study. AB - Immediate treatment of first-episode psychosis is essential in order to achieve a positive outcome. However, Indonesian psychiatric patients often delay accessing health services, the reason for which is not yet fully understood. The current study aimed to understand patterns of treatment seeking and to reveal determinants of the delay in accessing psychiatric care among first-time user psychotic patients. Qualitative interviews were conducted with sixteen family members who accompanied the patients to a psychiatric hospital. Many families expressed beliefs that mental illness appertains to village sickness and not hospital sickness; therefore, they usually take the patients to traditional or religious healers before taking them to a health professional. They also identified various factors that potentially delay accessing psychiatric treatment: low literacy and beliefs about the cause of the illness, stigmatisation, the role of extended family, financial problems, and long distance to the psychiatric hospital. On the other hand, the family mentioned various factors related to timely help seeking, including being a well-educated family, living closer to health facilities, previous experience of successful psychotic therapy, and having more positive symptoms of psychosis. The findings call for mental health awareness campaigns in the community. PMID- 27382502 TI - Concerns around Brexit from the perspective of dentistry. PMID- 27382503 TI - Peri-implant disease: what we know and what we need to know. AB - Peri-implant disease is a serious problem that plagues today's dentistry, both in terms of therapy and epidemiology. With the expansion of the practice of implantology and an increasing number of implants placed annually, the frequency of peri-implant disease has greatly expanded. Its clinical manifestations, in the absence of a globally established classification, are peri-implant mucositis and peri-implantitis, the counterparts of gingivitis and periodontitis, respectively. However, many doubts remain about its features. Official diagnostic criteria, globally recognized by the dental community, have not yet been introduced. The latest studies using metagenomic methods are casting doubt on the assumption of microbial equivalence between periodontal and peri-implant crevices. Research on most of the features of peri-implant disease remains at an early stage; moreover, there is not a commonly accepted treatment for it. In any case, although the evidence so far collected is limited, we need to be aware of the current state of the science regarding this topic to better understand and ultimately prevent this disease. PMID- 27382504 TI - The effects of bone density and crestal cortical bone thickness on micromotion and peri-implant bone strain distribution in an immediately loaded implant: a nonlinear finite element analysis. AB - PURPOSE: This study investigated the effects of bone density and crestal cortical bone thickness at the implant-placement site on micromotion (relative displacement between the implant and bone) and the peri-implant bone strain distribution under immediate-loading conditions. METHODS: A three-dimensional finite element model of the posterior mandible with an implant was constructed. Various bone parameters were simulated, including low or high cancellous bone density, low or high crestal cortical bone density, and crestal cortical bone thicknesses ranging from 0.5 to 2.5 mm. Delayed- and immediate-loading conditions were simulated. A buccolingual oblique load of 200 N was applied to the top of the abutment. RESULTS: The maximum extent of micromotion was approximately 100 MUm in the low-density cancellous bone models, whereas it was under 30 MUm in the high-density cancellous bone models. Crestal cortical bone thickness significantly affected the maximum micromotion in the low-density cancellous bone models. The minimum principal strain in the peri-implant cortical bone was affected by the density of the crestal cortical bone and cancellous bone to the same degree for both delayed and immediate loading. In the low-density cancellous bone models under immediate loading, the minimum principal strain in the peri implant cortical bone decreased with an increase in crestal cortical bone thickness. CONCLUSIONS: Cancellous bone density may be a critical factor for avoiding excessive micromotion in immediately loaded implants. Crestal cortical bone thickness significantly affected the maximum extent of micromotion and peri implant bone strain in simulations of low-density cancellous bone under immediate loading. PMID- 27382505 TI - Preferences and flexibility in decision-making among dental clinicians regarding the treatment of multirooted teeth: an interactive communication device-based survey at two academic conferences. AB - PURPOSE: Decision-making by dental and medical experts can be influenced by their biases, interests, and experiences, and academic arguments about controversial issues may additionally be considered indirect experiences capable of affecting decision-making. This study reports on the use of interactive communication devices to evaluate preferences and flexibility in decision-making among dental care providers who attended two distinct academic conferences. METHODS: Two debates were presented by a team of two lecturers at two academic conferences (focusing on periodontology and implant dentistry, respectively) and the audience members of each session were surveyed. Before each lecture, two case modules about the diagnosis and treatment of multirooted molar lesions were provided, and interactive communication devices were used to collect responses about decision making preferences in treatment planning immediately before and after a debate about treatment strategies. RESULTS: In total, 81 and 84 completed answers from both conferences were obtained for the first and second case modules, respectively. The preferred treatment plan differed significantly according to the focus of the conference, and a tendency emerged for the clinicians participating in each conference to express uniform preferences. However, attending the debates resulted in significant changes in decision-making preferences regardless of the conference focus or the characteristics of the participants. CONCLUSIONS: Our findings suggest that providing continuing education via debates on controversial issues may be effective in widening conceptual knowledge and reducing biases among experts in the dental and medical fields. PMID- 27382506 TI - Evaluation of bone substitutes for treatment of peri-implant bone defects: biomechanical, histological, and immunohistochemical analyses in the rabbit tibia. AB - PURPOSE: We sought to evaluate the effectiveness of bone substitutes in circumferential peri-implant defects created in the rabbit tibia. METHODS: Thirty rabbits received 45 implants in their left and right tibia. A circumferential bone defect (6.1 mm in diameter/4 mm depth) was created in each rabbit tibia using a trephine bur. A dental implant (4.1 mm * 8.5 mm) was installed after the creation of the defect, providing a 2-mm gap. The bone defect gaps between the implant and the bone were randomly filled according to the following groups: blood clot (CO), particulate Bio-Oss((r)) (BI), and Bio-Oss((r)) Collagen (BC). Ten animals were euthanized after periods of 15, 30, and 60 days. Biomechanical analysis by means of the removal torque of the implants, as well as histologic and immunohistochemical analyses for protein expression of osteocalcin (OC), Runx2, OPG, RANKL, and TRAP were evaluated. RESULTS: For biomechanics, BC showed a better biological response (61.00+/-15.28 Ncm) than CO (31.60+/-14.38 Ncm) at 30 days. Immunohistochemical analysis showed significantly different OC expression in CO and BC at 15 days, and also between the CO and BI groups, and between the CO and BC groups at 60 days. After 15 days, Runx2 expression was significantly different in the BI group compared to the CO and BC groups. RANKL expression was significantly different in the BI and CO groups and between the BI and BC groups at 15 days, and also between the BI and CO groups at 60 days. OPG expression was significantly higher at 60 days postoperatively in the BI group than the CO group. CONCLUSIONS: Collectively, our data indicate that, compared to CO and BI, BC offered better bone healing, which was characterized by greater RUNX2, OC, and OPG immunolabeling, and required greater reversal torque for implant removal. Indeed, along with BI, BC presents promising biomechanical and biological properties supporting its possible use in osteoconductive grafts for filling peri-implant gaps. PMID- 27382507 TI - Alterations of papilla dimensions after orthodontic closure of the maxillary midline diastema: a retrospective longitudinal study. AB - PURPOSE: The aim of this study was to evaluate alterations of papilla dimensions after orthodontic closure of the diastema between maxillary central incisors. METHODS: Sixty patients who had a visible diastema between maxillary central incisors that had been closed by orthodontic approximation were selected for this study. Various papilla dimensions were assessed on clinical photographs and study models before the orthodontic treatment and at the follow-up examination after closure of the diastema. Influences of the variables assessed before orthodontic treatment on the alterations of papilla height (PH) and papilla base thickness (PBT) were evaluated by univariate regression analysis. To analyze potential influences of the 3-dimensional papilla dimensions before orthodontic treatment on the alterations of PH and PBT, a multiple regression model was formulated including the 3-dimensional papilla dimensions as predictor variables. RESULTS: On average, PH decreased by 0.80 mm and PBT increased after orthodontic closure of the diastema (P<0.01). Univariate regression analysis revealed that the PH (P=0.002) and PBT (P=0.047) before orthodontic treatment influenced the alteration of PH. With respect to the alteration of PBT, the diastema width (P=0.045) and PBT (P=0.000) were found to be influential factors. PBT before the orthodontic treatment significantly influenced the alteration of PBT in the multiple regression model. CONCLUSIONS: PH decreased but PBT increased after orthodontic closure of the diastema. The papilla dimensions before orthodontic treatment influenced the alterations of PH and PBT after closure of the diastema. The PBT increased more when the diastema width before the orthodontic treatment was larger. PMID- 27382508 TI - Geographic information system analysis on the distribution of patients visiting the periodontology department at a dental college hospital. AB - PURPOSE: The aim of this study is to analyze and visualize the distribution of patients visiting the periodontology department at a dental college hospital, using a geographic information system (GIS) to utilize these data in patient care and treatment planning, which may help to assess the risk and prevent periodontal diseases. METHODS: Basic patient information data were obtained from Dankook University Dental Hospital, including the unit number, gender, date of birth, and address, down to the dong (neighborhood) administrative district unit, of 306,656 patients who visited the hospital between 2007 and 2014. The data of only 26,457 patients who visited the periodontology department were included in this analysis. The patient distribution was visualized using GIS. Statistical analyses including multiple regression, logistic regression, and geographically weighted regression were performed using SAS 9.3 and ArcGIS 10.1. Five factors, namely proximity, accessibility, age, gender, and socioeconomic status, were investigated as the explanatory variables of the patient distribution. RESULTS: The visualized patient data showed a nationwide scale of the patient distribution. The mean distance from each patient's regional center to the hospital was 30.94+/-29.62 km and was inversely proportional to the number of patients from the respective regions. The distance from a regional center to the adjacent toll gate had various effects depending on the local distance from the hospital. The average age of the patients was 52.41+/-12.97 years. Further, a majority of regions showed a male dominance. Personal income had inconsistent results between analyses. CONCLUSIONS: The distribution of patients is significantly affected by the proximity, accessibility, age, gender and socioeconomic status of patients, and the patients visiting the periodontology department travelled farther distances than those visiting the other departments. The underlying reason for this needs to be analyzed further. PMID- 27382509 TI - Poly(ADP-ribose) polymerase regulates glycolytic activity in kidney proximal tubule epithelial cells. AB - After renal injury, selective damage occurs in the proximal tubules as a result of inhibition of glycolysis. The molecular mechanism of damage is not known. Poly(ADP-ribose) polymerase (PARP) activation plays a critical role of proximal tubular cell death in several renal disorders. Here, we studied the role of PARP on glycolytic flux in pig kidney proximal tubule epithelial LLC-PK1 cells using XFp extracellular flux analysis. Poly(ADP-ribosyl)ation by PARP activation was increased approximately 2-fold by incubation of the cells in 10 mM glucose for 30 minutes, but treatment with the PARP inhibitor 3-aminobenzamide (3-AB) does dependently prevented the glucose-induced PARP activation (approximately 14.4% decrease in 0.1 mM 3-AB-treated group and 36.7% decrease in 1 mM 3-AB-treated group). Treatment with 1 mM 3-AB significantly enhanced the glucose-mediated increase in the extracellular acidification rate (61.1+/-4.3 mpH/min vs. 126.8+/ 6.2 mpH/min or approximately 2-fold) compared with treatment with vehicle, indicating that PARP inhibition increases only glycolytic activity during glycolytic flux including basal glycolysis, glycolytic activity, and glycolytic capacity in kidney proximal tubule epithelial cells. Glucose increased the activities of glycolytic enzymes including hexokinase, phosphoglucose isomerase, phosphofructokinase-1, glyceraldehyde-3-phosphate dehydrogenase, enolase, and pyruvate kinase in LLC-PK1 cells. Furthermore, PARP inhibition selectively augmented the activities of hexokinase (approximately 1.4-fold over vehicle group), phosphofructokinase-1 (approximately 1.6-fold over vehicle group), and glyceraldehyde-3-phosphate dehydrogenase (approximately 2.2-fold over vehicle group). In conclusion, these data suggest that PARP activation may regulate glycolytic activity via poly(ADP-ribosyl)ation of hexokinase, phosphofructokinase 1, and glyceraldehyde-3-phosphate dehydrogenase in kidney proximal tubule epithelial cells. PMID- 27382510 TI - Vitamin C is taken up by human T cells via sodium-dependent vitamin C transporter 2 (SVCT2) and exerts inhibitory effects on the activation of these cells in vitro. AB - Vitamin C is an essential micronutrient that affects immune responses. T cells are one of the main players in acquired immunity and have been reported to be influenced by in vivo vitamin C supplementation. Yet, the way by which T cells uptake vitamin C and what direct effects vitamin C exerts on the cells are not known. To elucidate, we isolated human peripheral blood T cells and analyzed the expression of sodium-dependent vitamin C transporters (SVCT). T cells were activated in vitro in the absence or presence of vitamin C, before or after activation. As results, human T cells expressed SVCT2, but not SVCT1, and the expression level increased following activation. Vitamin C added in the culture media generally did not affect T-cell behaviors following activation, such as proliferation, apoptosis, expression of CD25 and CD69, and interleukin 2 secretion, regardless whether it was added before or after activation. However, exceptionally, high concentration vitamin C, when it was added before activation, but not after activation, did exert toxic effects on cell activation with respect to the above-mentioned parameters. In conclusion, we showed the expression of SVCT2 in human T cells for the first time. Vitamin C exerted toxic effects, at least in vitro, when the concentration was high and when it was given before activation. These toxic effects are not thought to be via anti-oxidant effects of vitamin C. PMID- 27382511 TI - Changes in expression of proteasome in rats at different stages of atherosclerosis. AB - It has been suggested that proteasome system has a role in initiation, progression, and complication stages of atherosclerosis. Although there is still controversy, there has been no research that compares the expression of proteasome in tissue and serum at each of these stages. This study aimed to investigated the expression of proteasome at different stages of atherosclerosis using rat model. We measured the expression of aortic proteasome by immunohistochemical analyses and were then analyzed using ImageJ software for percentage of area and integrated density. We used Photoshop version 3.0 to analyze aortic proteasome expression as a comparison. We measured serum proteasome expression by enzyme linked immunosorbents assays. Kruskal-Wallis test was used to compare mean value of percentage of area and serum proteasome. Analysis of variance test was used to compare mean value of integrated density. Correlation test between vascular proteasome expression and serum proteasome expression was made using Spearman test. A P-value of 0.05 was considered statistically significant. Compared with normal, percentage of area was higher in initiation, progression, and complication. Compared with normal, integrated density was higher in initiation and further higher in progression and complication. Data from Image J is similar with data from Photoshop. Serum proteasome expression was higher in initiation compared with normal, and further higher in progression and complication. It was concluded that there were different vascular proteasome expression and serum proteasome expression at the stages of atherosclerosis. These results may be used in research into new marker and therapeutic target in atherosclerosis. PMID- 27382512 TI - 5-Aza-2'-deoxycytidine acts as a modulator of chondrocyte hypertrophy and maturation in chick caudal region chondrocytes in culture. AB - This study was carried out to explore the effect of DNA hypomethylation on chondrocytes phenotype, in particular the effect on chondrocyte hypertrophy, maturation, and apoptosis. Chondrocytes derived from caudal region of day 17 embryonic chick sterna were pretreated with hypomethylating drug 5-aza-2' deoxycytidine for 48 hours and then maintained in the normal culture medium for up to 14 days. Histological studies showed distinct morphological changes occurred in the pretreated cultures when compared to the control cultures. The pretreated chondrocytes after 7 days in culture became bigger in size and acquired more flattened fibroblastic phenotype as well as a loss of cartilage specific extracellular matrix. Scanning electron microscopy at day 7 showed chondrocytes to have increased in cell volume and at day 14 in culture the extracellular matrix of the pretreated cultures showed regular fibrillar structure heavily embedded with matrix vesicles, which is the characteristic feature of chondrocyte hypertrophy. Transmission electron microscopic studies indicated the terminal fate of the hypertrophic cells in culture. The pretreated chondrocytes grown for 14 days in culture showed two types of cells: dark cells which had condense chromatin in dark patches and dark cytoplasm. The other light chondrocytes appeared to be heavily loaded with endoplasmic reticulum indicative of very active protein and secretory activity; their cytoplasm had large vacuoles and disintegrating cytoplasm. The biosynthetic profile showed that the pretreated cultures were actively synthesizing and secreting type X collagen and alkaline phosphatase as a major biosynthetic product. PMID- 27382513 TI - Perineal raphe with special reference to its extension to the anus: a histological study using human fetuses. AB - The raphe of the human penis and scrotum is considered to develop secondarily after disappearance of the initial midline seam by fusion of the bilateral genital folds. However, the fetal development was still obscure. We examined histological sections of 30 fetuses (17 males and 13 females) at 10-15 weeks. In male fetuses, the scrotum was not yet clearly identified because of no descent of testis. The perineal raphe was thin and wavy at 10 weeks, and it was continuous with and took a direction same as the inferior wall of the closed penile urethra after physiological hypospadias. Depending on growth of the bulbospongiosus muscle and corpus spongiosus penis, the midline intermuscular septum obtained a connection to the subcutaneous wavy raphe and made the latter thick and straight at 12-15 weeks. Notably, the perineal raphe extended posteriorly to attach to the external anal sphincter. In female fetuses, an epithelial fusion occurred along a short distance at the posterior end of the vestibule. However, in front of the external anal sphincter, a large midline mesenchymal tissue from the urorectal septum did not contain a raphe-like structure. Moreover, since the bilateral bulbospongiosus muscles were separated widely by the vestibule, they did not provide a midline septum. Fetal development of the perineal raphe was accelerated by reinforcement from the muscular septum. In contrast, without such a muscular support, the female raphe could not maintain its growth even if the seed appeared at the posterior end of the vestibule. PMID- 27382514 TI - Vertical and horizontal facial proportions of Indian American men. AB - The importance of understanding all gender facial differences is critical in providing a successful cosmetic outcome. Men are a growing segment of the cosmetic industry. Understanding of the male face and its appropriate treatment with minimally invasive cosmetic procedures are essential. The aim was to investigate various facial ratios in Indian American men and to compare them with the Indian and Caucasian norms. Additionally, we wanted to evaluate whether these values satisfy golden and silver ratios. Direct facial anthropometric measurements were made using a digital caliper in 100 Indian American men students (18-30 years) at the American University of Antigua (AUA), Antigua. A set of facial ratios were calculated and compared with coefficients of variation (CV). Most of the facial ratios had small CV thus making them highly reliable due to reduced intra-sample variability. The upper face to face height and mandibulo upper face height indices were close to golden ratios whereas mandibulo lower face height, upper face height biocular width, and nasal indices were close to silver ratios. There was significant difference in most of the values when compared with previous studies. The present facial ratios data can be used as a reference value for Indian American men. PMID- 27382515 TI - Human nasociliary nerve with special reference to its unique parasympathetic cutaneous innervation. AB - The frontal nerve is characterized by its great content of sympathetic nerve fibers in contrast to cutaneous branches of the maxillary and mandibular nerves. However, we needed to add information about composite fibers of cutaneous branches of the nasociliary nerve. Using cadaveric specimens from 20 donated cadavers (mean age, 85), we performed immunohistochemistry of tyrosine hydroxylase (TH), neuronal nitric oxide synthase (nNOS), and vasoactive intestinal polypeptide (VIP). The nasocilliary nerve contained abundant nNOS positive fibers in contrast to few TH- and VIP-positive fibers. The short ciliary nerves also contained nNOS-positive fibers, but TH-positive fibers were more numerous than nNOS-positive ones. Parasympathetic innervation to the sweat gland is well known, but the original nerve course seemed not to be demonstrated yet. The present study may be the first report on a skin nerve containing abundant nNOS-positive fibers. The unique parasympathetic contents in the nasocilliary nerve seemed to supply the forehead sweat glands as well as glands in the eyelid and nasal epithelium. PMID- 27382516 TI - Anatomical considerations of the superior thyroid artery: its origins, variations, and position relative to the hyoid bone and thyroid cartilage. AB - The aim of this study was to provide accurate anatomical descriptions of the overall anatomy of the superior thyroid artery (STA), its relationship to other structures, and its driving patterns. Detailed dissection was performed on thirty specimens of adult's cadaveric neck specimens and each dissected specimen was carefully measured the following patterns and distances using digital and ruler. The superior thyroid, lingual, and facial arteries arise independently from the external carotid artery (ECA), but can also arise together, as the thyrolingual or linguofacial trunk. We observed that 83.3% of STAs arose independently from the major artery, while 16.7% of the cases arose from thyrolingual or linguofacial trunk. We also measured the distance of STA from its major artery. The origin of the STA from the ECA was 0.9+/-0.4 mm below the hyoid bone. The STA was 4.4+/-0.5 mm distal to the midline at the level of the laryngeal prominence and 3.1+/-0.6 mm distal to the midline at the level of the inferior border of thyroid cartilage. The distance between STA and the midline was similar at the level of the hyoid bone and the thyroid cartilage. Also, when the STA is near the inferior border of the thyroid cartilage, it travels at a steep angle to the midline. This latter point may be particularly important in thyroidectomies. We hope that anatomical information provided here will enhance the success of, and minimize complications in, surgeries that involve STA. PMID- 27382517 TI - Incidence of pterygospinous and pterygoalar bridges in dried skulls of Koreans. AB - Understanding of morphological structures such as the sphenoid spine and pterygoid processes is important during lateral transzygomatic infratemporal fossa approach. In addition, osseous variations such as pterygospinous and pterygoalar bridges are significant in clinical practice because they can produce various neurological disturbances or block the passage of a needle into the trigeminal ganglion through the foramen ovale. Two hundred and eighty-four sides of Korean adult dry skulls were observed to carry out morphometric analysis of the lateral plate of the pterygoid process, to investigate, for the first time among Koreans, the incidence of the pterygospinous and pterygoalar bony bridges, to compare the results with those available for other regional populations, and to discuss their clinical relevance as described on literatures. The mean of maximum widths of the left and right lateral plates of the pterygoid process were 15.99 mm and 16.27 mm, respectively. Also, the mean of maximum heights of the left and right lateral plates were 31.02 mm and 31.01 mm, respectively. The ossified pterygospinous ligament was observed in 51 sides of the skulls (28.0%). Ossification of the pterygospinous ligament was complete in four sides (1.4%). In 47 sides (16.6%), the pterygospinous bridge was incomplete. The ossified pterygoalar ligament was observed in 24 sides of the skulls (8.4%). Ossification was complete in eight sides (2.8%) and incomplete in 16 sides (5.6%). This detailed analysis of the lateral plate of the pterygoid process and related ossification of ligaments can improve the understanding of complex clinical neuralgias associated with this region. PMID- 27382518 TI - Binary logistic regression analysis of hard palate dimensions for sexing human crania. AB - Sex determination is the preliminary step in every forensic investigation and the hard palate assumes significance in cranial sexing in cases involving burns and explosions due to its resistant nature and secluded location. This study analyzes the sexing potential of incisive foramen to posterior nasal spine length, palatine process of maxilla length, horizontal plate of palatine bone length and transverse length between the greater palatine foramina. The study deviates from the conventional method of measuring the maxillo-alveolar length and breadth as the dimensions considered in this study are more heat resistant and useful in situations with damaged alveolar margins. The study involves 50 male and 50 female adult dry skulls of Indian ethnic group. The dimensions measured were statistically analyzed using Student's t test, binary logistic regression and receiver operating characteristic curve. It was observed that the incisive foramen to posterior nasal spine length is a definite sex marker with sex predictability of 87.2%. The palatine process of maxilla length with 66.8% sex predictability and the horizontal plate of palatine bone length with 71.9% sex predictability cannot be relied upon as definite sex markers. The transverse length between the greater palatine foramina is statistically insignificant in sexing crania (P=0.318). Considering a significant overlap of values in both the sexes the palatal dimensions singularly cannot be relied upon for sexing. Nevertheless, considering the high sex predictability of incisive foramen to posterior nasal spine length this dimension can definitely be used to supplement other sexing evidence available to precisely conclude the cranial sex. PMID- 27382520 TI - Erratum: The association between PGC-1alpha and Alzheimer's disease. AB - [This corrects the article on p. 1 in vol. 49, PMID: 27051562.]. PMID- 27382519 TI - Muscular axillary arch accompanying variation of the musculocutaneous nerve: axillary arch. AB - Continuous attention has been developed on the anatomical variations of the axilla in anatomist and surgeon due to their clinical importance. The axillary region is an anatomical space between the lateral part of the chest wall and the medial aspect of the upper limb. During the routine dissection of embalmed cadavers, we found variant muscular slip originating from the lateral border of tendinous part of the latissimus dorsi and continuing 9 cm more crossing the axilla. And then, it inserted into the superior margin of the insertion of the pectoralis major. We considered this muscular variation as axillary arch muscle. Correct identification of the relevant anatomy and subsequent simple surgical division is curative, paying special attention to anatomical variations in this region and its clinical importance due to its close relationship to the neurovascular elements of the axilla. PMID- 27382521 TI - A rare intracranial tumor consisting of malignant anaplastic and papillary meningioma subtypes. PMID- 27382522 TI - Never giving up. PMID- 27382523 TI - Hypertonicity: Pathophysiologic Concept and Experimental Studies. AB - Disturbances in tonicity (effective osmolarity) are the major clinical disorders affecting cell volume. Cell shrinking secondary to hypertonicity causes severe clinical manifestations and even death. Quantitative management of hypertonic disorders is based on formulas computing the volume of hypotonic fluids required to correct a given level of hypertonicity. These formulas have limitations. The major limitation of the predictive formulas is that they represent closed system calculations and have been tested in anuric animals. Consequently, the formulas do not account for ongoing fluid losses during development or treatment of the hypertonic disorders. In addition, early comparisons of serum osmolality changes predicted by these formulas and observed in animals infused with hypertonic solutions clearly demonstrated that hypertonicity creates new intracellular solutes causing rises in serum osmolality higher than those predicted by the formulas. The mechanisms and types of intracellular solutes generated by hypertonicity and the effects of the solutes have been studied extensively in recent times. The solutes accumulated intracellularly in hypertonic states have potentially major adverse effects on the outcomes of treatment of these states. When hypertonicity was produced by the infusion of hypertonic sodium chloride solutions, the predicted and observed changes in serum sodium concentration were equal. This finding justifies the use of the predictive formulas in the management of hypernatremic states. PMID- 27382524 TI - Incidence of Intracranial Hemorrhage After a Cranial Operation. AB - OBJECTIVE: To describe the characteristics of patients who underwent a cranial operation and postoperatively suffered an intracranial hemorrhage significant enough to require evacuation. MATERIALS & METHODS : 3,109 cranial operations were performed at Houston Methodist Hospital (Texas Medical Center campus) between January 2009 and December 2013. Of these, 59 cases required a second operation for evacuation of an intracranial hemorrhage. The information gathered included the patients' age, gender, past medical history, medications and laboratory data, initial diagnosis, date/type of first and second operations, duration of hospitalization, discharge condition, and discharge destination. RESULTS: The study found a 1.90% rate of a postoperative hemorrhage significant enough to require evacuation after a cranial operation. The average age in the cohort requiring reoperation was 63 +/- 14 years with 42 male and 17 female. Hematoma evacuations were performed at various time intervals depending on the pathology treated at the initial operation. The time to second operation was 2.7 days after intraparenchymal hematoma evacuation, 6.0 days after cerebrovascular surgery, 6.2 days after tumor surgery and 9.7 days after subdural hematoma evacuation. The rate of postoperative hematoma development was 9.1% after a subdural hematoma evacuation, while it was only 1.1% in all other operations. Overall, those requiring hematoma evacuation had a 15% mortality rate, 64% were non-ambulatory, and 54% were discharged to long-term acute care facility, skilled nursing facility, rehabilitation facility or hospice. CONCLUSIONS : Neurological outcomes were poor in patients who underwent a cranial operation and required a second operation to remove a hematoma. This study suggests close observation of elderly males after a cranial operation, especially after subdural hematoma evacuation, and longer observation time for patients undergoing subdural hematoma evacuation than intraparenchymal hematoma evacuation, tumor surgery or cerebrovascular surgery. PMID- 27382525 TI - Utilization of a New Intracranial Support Catheter as an Intermediate Aspiration Catheter in the Treatment of Acute Ischemic Stroke: Technical Report on Initial Experience. AB - The endovascular management of acute ischemic stroke (AIS) due to emergency large vessel occlusion (ELVO) has become the standard of care after the recent publication of landmark randomized, controlled trials. Mechanical thrombectomy, in addition to intravenous thrombolysis (within 4.5 hours when eligible), is now part of the algorithm of the standard of care when treating AIS in patients with ELVO in the anterior circulation up to six hours after symptom onset. A newly introduced device, the ArcTM intracranial support catheter (Medtronic, Irvine, USA), is specifically designed for the introduction of neurointerventional devices into the cerebral vasculature and facilitates the delivery of microcatheters into smaller, more distal intracranial vessels. This technical report describes the use of the ArcTM intracranial support catheter in the setting of AIS. PMID- 27382526 TI - A Novel Method for Quality Assurance of the Cyberknife Iris Variable Aperture Collimator. AB - OBJECTIVE: To characterize a novel method for field-size quality assurance of a variable approximately circular aperture collimator by means of dose-area product measurements and to validate its practical use over two years of clinical application. METHODS: To assess methodical limitations, we analyze measurement errors due to change in linac output, beam tuning, uncertainty in MU delivery, daily factors, inherent uncertainty of the large-area parallel-plate ionisation chamber, and misalignment of the large-area parallel-plate ionisation chamber relative to the primary beam axis. To establish a baseline for quality assurance, the dose-area product is measured with the large-area parallel-plate ionisation chamber for all 12 clinical iris apertures in relation to the 60 mm fixed reference aperture. To evaluate the long-term stability of the Iris collimation system, deviation from baseline data is assessed monthly and compared to a priori derived tolerance levels. RESULTS: Only chamber misalignment, variation in output, and uncertainty in MU delivery contribute to a combined error that is estimated at 0.2 % of the nominal field size. This is equivalent to a resolution of 0.005 mm for the 5 mm, and 0.012 mm for the 60 mm field. The method offers ease of use, small measurement time commitment, and is independent of most error sources. Over the observed period, the Iris accuray is within the tolerance levels. CONCLUSIONS: The method is an advantageous alternative to film quality assurance with a high reliability, short measurement time, and superior accuracy in field-size determination. PMID- 27382527 TI - Imaging, Endoscopic and Genetic Assessment of Marfan Syndrome Presenting with Sigmoid Volvulus: A Review. AB - The Marfan syndrome (MFS) is a pleiotropic, autosomal dominant disorder of connective tissue with highly variable clinical manifestations. It primarily involves the skeletal, cardiovascular, and ocular systems; however, gastrointestinal complications are rare. Herein, we describe the case of a 31 year-old male who initially presented with acute abdominal pain for one day. His imaging features revealed a dilated sigmoid colon, consistent with sigmoid volvulus that was immediately decompressed. Surgical resection was recommended to treat the sigmoid volvulus. Preceding the treatment, the patient underwent an extensive workup, including an echocardiography that revealed aortic root dilatation. His clinical history, physical exam, and echocardiographic findings raised the suspicion for MFS. Subsequently, the diagnosis of MFS was confirmed on genetic testing. This is a case that highlights the multidisciplinary (clinical, radiological, endoscopic, molecular/genetic) approach to diagnose a patient with MFS who presented with symptomatic sigmoid volvulus. As this presentation may be a harbinger of more severe manifestations of MFS, it is important to identify it as such in order to accomodate for timely management. PMID- 27382528 TI - Bromodomain Inhibitor Review: Bromodomain and Extra-terminal Family Protein Inhibitors as a Potential New Therapy in Central Nervous System Tumors. AB - The bromodomain and extraterminal (BET) family proteins associate with transcriptional activation through interaction with acetylated chromatin, therefore playing a key role as epigenetic regulators. BET proteins serve to regulate the expression of importance oncogenes, including those involved in apoptosis as well as cell cycle progression. Due to this potential as an epigenetic target, small molecule inhibition of BET proteins have been investigated and demonstrate promising activity in both solid and hematologic malignancies, including brain tumors. Glioblastoma multiforme (GBM), subsets of medulloblastoma, and diffuse intrinsic pontine glioma (DIPG) are types of brain tumors with dismal prognoses, and as such have been the subjects of preclinical studies using BET inhibitors both in vivo and in vitro. While results from these preclinical investigations have shown promise, clinical trials are in early phases at this time. In this review, we will summarize the current literature on BET family proteins, their potential as therapeutic targets in brain tumors as well as other malignancies, and the preclinical and clinical investigations that have been undertaken to date. PMID- 27382529 TI - Delayed Presentation of a Cervical Spinal Epidural Abscess of Dental Origin after a Fall in an Elderly Patient. AB - Spinal epidural abscesses are an uncommon cause of spinal cord injury but, depending on the size and presence of neurological deficits, urgent neurosurgical intervention may be required. We present a unique case of a patient presenting with a spinal epidural collection several days after a fall. While a spinal epidural hematoma was suspected based on the patient's history and MRI findings, a spinal epidural abscess was found during surgery. The patient underwent laminectomy and instrumented fusion with successful treatment of her infection. PMID- 27382530 TI - Treatment of Recurrent Disc Herniation: A Systematic Review. AB - Intervertebral disc herniation is one of the most common causes of back and extremity pain. The most commonly used surgical treatment is lumbar discectomy. About 0.5-25% go on to develop recurrent disc herniation (rDH) after a successful first discectomy. Currently, there aren't any guidelines to assist surgeons in determining which approach is most appropriate to treat rDH. A recent survey showed significant heterogeneity among surgeons regarding treatment options for rDH. It remains unclear which methods lead to better outcomes, as there are no comparative studies with a sufficient level of evidence. In this study, we aimed to perform a systematic review to compare treatment options for rDH and determine if one intervention provides better outcomes than the other; more specifically, whether outcome differences exist between discectomy alone and discectomy with fusion. We applied the PICOS (participants, intervention, comparison, outcome, study design) format to develop this systematic review through PubMed. Twenty seven papers from 1978-2014 met our inclusion criteria and were included in the analysis. Nine papers reported outcomes after discectomy and seven of them showed good or excellent outcomes (70.60%-89%). Ten papers reported on minimally invasive discectomy. The percent change in visual analog scale (VAS) ranged from 50.77% to -86.57%, indicating an overall pain reduction. Four studies out of the ten reported good or excellent outcomes (81% to 90.2%). Three studies looked at posterolateral fusion. Three studies analyzed posterior lumbar interbody fusion. For one study, we found the VAS percentage change to be -46.02%. All reported good to excellent outcomes. Six studies evaluated the transforaminal lumbar interbody fusion. All reported improvement in pain. Four used VAS, and we found the percent change to be -54% to -86.5%. The other two used the Japanese Orthopedic Association (JOA) score, and we found the percent change to be 68.3% to 93.3%. We did not find enough evidence to support any significant difference in outcomes between discectomy alone and discectomy with fusion. The limitation of our study includes the lack of standardized outcomes reporting in the literature. However, reviewing the selected articles shows that fusion may have a greater improvement in pain compared to reoperation without fusion. Nonetheless, our study shows that further and more in-depth investigation is needed on the of treatment of rDH. PMID- 27382531 TI - Are dentists involved in the treatment of obesity? AB - The morbidity and mortality associated with being overweight or obese have been known to the medical profession to be related with an increased risk of associated diseases. This article provides an overview of obesity and addresses possible strategies for the management of this important public health concern. This narrative review sheds light on the problem of obesity and the necessity of professional oral health care to work in partnership with the medical team for managing obesity. In this regard, general dental practitioners should at least reinforce their knowledge regarding obesity and understand their potential role in the treatment and management of obese patients. PMID- 27382532 TI - Effect of anodization and alkali-heat treatment on the bioactivity of titanium implant material (an in vitro study). AB - OBJECTIVE: This study was aimed to assess the effect of anodized and alkali-heat surface treatment on the bioactivity of titanium alloy (Ti-6Al-4V) after immersion in Hank's solution for 7 days. MATERIALS AND METHODS: Fifteen titanium alloy samples were used in this study. The samples were divided into three groups (five for each), five samples were anodized in 1M H3PO4 at constant voltage value of 20 v and another five samples were alkali-treated in 5 M NaOH solution for 25 min at temperature 60 degrees C followed by heat treatment at 600 degrees C for 1 h. All samples were then immersed in Hank's solution for 7 days to assess the effect of surface modifications on the bioactivity of titanium alloy. The different treated surfaces and control one were characterized by X-ray diffraction, atomic force microscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy, and Fourier transformation infra-red spectroscopy. Statistical analysis was performed with PASW Statistics 18.0((r)) (Predictive Analytics Software). RESULTS: Anodization of Ti-alloy samples (Group B) led to the formation of bioactive titanium oxide anatase phase and PO4 (3-) group on the surface. The alkali-heat treatment of titanium alloy samples (Group C) leads to the formation of bioactive titania hydrogel and supplied sodium ions. The reaction between the Ti sample and NaOH alkaline solution resulted in the formation of a layer of amorphous sodium titania on the Ti surface, and this layer can induce apatite deposition. CONCLUSIONS: The surface roughness and surface chemistry had an excellent ability to induce bioactivity of titanium alloy. The anodization in H3PO4 produced anatase titanium oxide on the surface with phosphate originated from electrolytes changed the surface topography and allowed formation of calcium-phosphate. PMID- 27382533 TI - Comparative evaluation of antimicrobial effect of herbal root canal irrigants (Morinda citrifolia, Azadirachta indica, Aloe vera) with sodium hypochlorite: An in vitro study. AB - AIM AND OBJECTIVES: Successful root canal treatment involves the complete elimination of microorganism from the root canal and the three-dimensional obturation of the canal space. Enterococcus faecalis is the most commonly found bacteria in failed root canal. Chemical irrigation of canals along with biomechanical preparation helps in the elimination of microorganisms. The present study was aimed to evaluate the antimicrobial effect of herbal root canal irrigants (Morinda citrifolia, Azadirachta indica extract, Aloe vera) with sodium hypochlorite (NaOCl). MATERIALS AND METHODS: The bacterial E. faecalis (ATCC) culture was grown overnight in brain heart infusion (BHI) broth and inoculated in Mueller-Hinton agar plates. Antibacterial inhibition was assessed using agar well diffusion method. All five study irrigants were added to respective wells in agar plates and incubated at 37 degrees C for 24 h. Bacterial inhibition zone around each well was recorded. Results were tabulated and statistically analyzed using Statistical Package for the Social Sciences software for Windows, version 19.0. (IBM Corp., Armonk, NY. RESULTS: Highest inhibitory zone against E. faecalis was seen in NaOCl fallowed by M. citrifolia and A. indica extract, and the least by A. vera extract. CONCLUSION: Tested herbal medicine (A. indica extract, M. citrifolia, A. vera) showed inhibitory zone against E. faecalis. Hence, these irrigants can be used as root canal irrigating solutions. PMID- 27382534 TI - A novel Chotta Bheem-Chutki scale for dental anxiety determination in children. AB - OBJECTIVE: A potential problem in patient management in pediatric dentistry is dental anxiety among children. It is of paramount importance for pediatric dentists to identify an anxious child and review potential management options specific to every child. The aim of this study is to validate a newly devised Chotta Bheem-Chutki (CBC) pictorial scale and to compare this with Venham's pictorial scale (VPS) and facial image scale (FIS) to measure dental anxiety in young children during their first dental visit. MATERIALS AND METHODS: One hundred children aged 4-12 years were randomly selected from our hospital outpatient department. Child's anxiety levels were measured using three different scales; the VPS, FIS, and the newly devised CBC pictorial scale. The scores were recorded by asking the children to choose the figure they identified with at that instant. The scores obtained from all the three scales were compared using student's t-test. Pearson correlation test was used to obtain correlation among the scales used in the study. RESULTS: A strong correlation (0.778) was found between FIS and CBC scale. Moreover, a strong correlation (0.811) was found between VPS and CBC scale, indicating good validity of the CBC scale. Seventy five percent of the children found CBC scale to be the easiest among the three scales. CONCLUSION: The findings of this study suggest that CBC scale can be used as a new tool for dental anxiety assessment in children. PMID- 27382535 TI - Evaluation of the effect of hydrogen peroxide as a mouthwash in comparison with chlorhexidine in chronic periodontitis patients: A clinical study. AB - AIMS AND OBJECTIVE: This study was conducted to evaluate the effect of hydrogen peroxide (H2O2) as a mouthwash in comparison with chlorhexidine (CHX) in chronic periodontitis patients. MATERIALS AND METHODS: A total of 45 patients suffering from localized mild to moderate chronic periodontitis were chosen. The subjects were divided equally into three groups. Group A patients were treated only with scaling and root planning (SRP). Group B were treated with SRP in combination with 0.2% CHX gluconate mouthwash twice daily for 10 days. Group C were treated with SRP in combination with 1.5% H2O2 mouthwash twice daily for 10 days. Gingival index, plaque index, pocket depth, and clinical attachment level were recorded for patients of all groups on day 0 (Baseline), 15, 30, and 90, respectively. Statistical analysis was done using the Statistical Package for the Social Sciences version 22.0. Repeated measures analysis of variance was used to assess the differences in the abovementioned indices because of time and groups. RESULTS: Both CHX gluconate and H2O2 mouthwashes significantly reduced the gingival index more than that observed in the control group, but similar to each other. There were no significant differences in the clinical attachment loss, plaque index, and pocket depth among the study groups, but improvement was seen within the CHX group participants. In participants with chronic periodontitis, SRP in combination with 0.2% CHX gluconate mouthwash was an effective treatment in reducing the gingival index and the pocket depth, as well as improving the clinical attachment level. CONCLUSION: The use of CHX gluconate was observed to be higher than H2O2 for the reduction in the gingival index and the pocket depth, as well as for the improvement of the clinical attachment level. PMID- 27382536 TI - Oral health status and treatment needs among 10126 school children in West Godavari district, Andhra Pradesh, India. AB - OBJECTIVES: Oral diseases are affecting a large percentage of children worldwide. This study with Indian Society of Pedodontics and Preventive Dentistry collaboration was taken up with the aim to evaluate the oral health status and treatment needs in school-going children of the West Godavari district, Andhra Pradesh, India. MATERIALS AND METHODS: This cross-sectional study was conducted among 10126 school children who were randomly selected from 32 schools in West Godavari district. To find the significance of the obtained number of cases for different age groups, Chi-square test of significance was used. RESULTS: The prevalence of dental conditions are as follows: Dental caries 63.5%, periodontal diseases 13.6%, dental anomalies 3.6%, dental trauma 3.2%, and orthodontic treatment 25.1%. Among the different age groups, 11-14 years age group has the highest prevalence of oral health problems. Females were more affected with dental caries (P = 0.17), orthodontic treatment needs (P = 0.12), and dental anomalies (P = 0.86) compared to males which was statistically insignificant. The highest prevalence of dental conditions in the case of females was observed during the age of 11-14 years, and in males, the peak was seen in the 15-18 years age group. CONCLUSIONS: This study demonstrated that school-going children in West Godavari district suffer from a high prevalence of dental conditions and have higher treatment needs. PMID- 27382537 TI - Comparative evaluation of effect of complete denture wears on the flow rate of saliva in both medicated and apparently healthy patients. AB - AIM AND OBJECTIVES: In the denture wearing people, saliva is necessary to create adhesion, cohesion, and surface tension that ultimately leads to the increased retention of the denture. Medications have some influence on the flow rate of saliva and denture retention. The present study evaluates the effect of complete denture wear on the flow rate of saliva in both medicated and apparently healthy patients. MATERIALS AND METHODS: The participants were 42 edentulous individuals aged 35-70 years requiring complete denture prostheses. The participants were divided into two groups of medicated and unmedicated. Unstimulated whole saliva was collected at 24 h and 3 months after the insertion of new complete dentures in both the groups. The data obtained were analyzed using Student's paired t-test and unpaired t-test. Intergroup changes were compared with unpaired t-test. Intragroup changes were compared with paired t-test using the Statistical Package for Social Sciences, version 22.0. RESULTS: In the unmedicated group, the mean salivary flow rate was high at 24 h after denture insertion when compared to before denture insertion (P = 0.001 VHS). In the medicated group, the observation was highly significant (P = 0.007 HS) 24 h after denture insertion and after 3 months (P = 0.02 S) when compared to before denture insertion. CONCLUSION: No significant difference in the salivary flow rate was found 3 months after denture insertion when compared to before denture insertion for both the medicated and unmedicated groups. PMID- 27382538 TI - Discontinued dental attendance among elderly people in Sweden. AB - AIM: Our objective was to study the loss of dental attendance and a possible age trend among patients aged >=65 years in Sweden. Regular dental check-ups are considered to be an important factor in maintaining oral health. Approximately 80% of the adult population in Sweden are enrolled in a regular check-up system; however, dental practitioners often find that older patients attend fewer check ups. Old people may naturally lose contact with dental services as they move to special housing or die. In this systematic study, these factors were investigated and used as exclusion criteria. MATERIALS AND METHODS: Data were collected for all patients (n = 4759) aged 65 or older from the electronic journal system in 3 large public dental clinics in 3 communities. Their dental records for the years 2004-2009 were studied longitudinally by 1 person at each clinic; 1111 patients were excluded (patients died during study period, wanted emergency care only, obtained special dental care allowance, moved from the community or moved to special housing, or left the clinic for another caregiver). The statistical analyses were performed using the Statistical Package for the Social Sciences version 21 (IBM). RESULTS: Of the 3648 patients (1690 men and 1958 women) included in the study, 13% lost contact with their dental service over the course of the study (10% of those were aged 65-79 and 21% >=80). The decrease in regular dental contact had a statistically significant association with increasing age (P < 0.001). CONCLUSION: A considerable number of older people living independently or with moderate supportive care in their own homes lost contact with dental service despite enrolment in a recall system. PMID- 27382539 TI - Prevalence of palatal rugae shapes in Karnataka and Kerala population: A cross sectional study. AB - AIMS AND OBJECTIVES: This study was conducted to assess the incidence and prevalence of palatal rugae shapes in the male and female populations of Karnataka and Kerala. MATERIALS AND METHODS: This study consisted of 100 plaster models of each group, which were equally distributed between both the genders, with an age range of 17-23 years. The rugae patterns were recorded by using Thomas and Kotze classification. Correlation between the rugae shape and population as well as the rugae shape and gender were analyzed using chi-square analysis and discriminant function analysis using the Statistical Package for the Social Sciences Version 22 (IBM Corp). RESULTS: Curved, straight, and wavy rugae patterns were the most common in both Kerala and Karnataka sample populations. Chi-square analysis showed significant differences between the populations for the curved pattern; discriminant function analysis showed significant differences between the populations for the curved and straight patterns. Significant gender differences were found in the curved pattern for Karnataka population and in unification patterns for both populations by Chi-square/Fischer exact test. CONCLUSIONS: The curved and straight rugae patterns were significantly more frequent in the Kerala population compared to the Karnataka population. Because of the limited sample size of this study, further cross-sectional studies are suggested. PMID- 27382540 TI - Vitamin D status and periodontal disease among pregnant and non-pregnant women in an underdeveloped district of Pakistan. AB - AIM: To compare pregnant and non-pregnant females for vitamin D level and periodontal status and to determine if there is any association between the periodontal health and hypovitaminosis D in pregnant women. MATERIALS AND METHODS: A cross-sectional study was conducted in Jhelum, Pakistan. Participants were pregnant females at ~ 12 weeks of gestation (n = 36) and non-pregnant (n = 35) females selected from the same locality. Periodontal parameters such as probing depth, bleeding on probing, and attachment loss were recorded. Serum samples were taken to measure blood indices and vitamin D levels. Chi-square test and Odds ratio were applied to determine the association between hypovitaminosis D and periodontal status. RESULTS: Vitamin D deficiency was common in the pregnant group compared to non-pregnant (P < 0.001). Blood indices (hemoglobin, hematocrit, mean corpuscular volume) were significantly lower among the pregnant compared to the non-pregnant group (P < 0.001). However, there was no significant difference between the two groups for probing depth and attachment loss. CONCLUSIONS: Pregnant women were more deficient in Vitamin D than non-pregnant women. However, no association between low vitamin D levels and periodontal disease was seen in the studied population. PMID- 27382541 TI - To evaluate the influence of smear layer with different instruments and obturation methods on microleakage of root canal filled teeth: In vitro study. AB - AIMS AND OBJECTIVES: The success of root canal treatment depends on proper debridement, instrumentation, proper accessibility, and proper restoration. The presence of a smear layer is considered to be a significant factor. This in vitro study was conducted to assess the effect of the presence/absence of a smear layer on the microleakage of root canal filled teeth using different instruments and obturation methods. MATERIALS AND METHODS: One hundred extracted mandibular premolars with closed apices and single roots were chosen and then divided into six groups, A to F, consisting of 15 teeth each. The control group included 10 teeth; 5 positive and 5 negative. The teeth were decoronated at the cementoenamel junction. Groups A, B, C, and D were instrumented with engine-driven rotary Protaper NiTi files. Groups E and F were instrumented with conventional stainless steel hand files. Groups A, C, and E were flushed with 3 ml of 17% EDTA to remove the smear layer prior to obturation. All teeth were flushed with 5.25% sodium hypochlorite solution and obturated with AH-Plus sealer with lateral condensation technique for Groups C, D, E, F and with thermoplasticized gutta-percha technique for Groups A and B. Using an electrochemical technique, leakages in the obturated canals were assessed for 45 days. The results were tabulated using Student's t test (paired and unpaired t-test) with the Statistical Package for the Social Sciences Software Version 21 (IBM Company, New York, USA). RESULTS: Group A showed the lowest mean value at intervals of 10, 20, 30, and 45 days. There was no current flow in the negative controls during the test period. There was leakage in the positive controls within a few minutes of immersion. CONCLUSION: The results showed that rotary instrumentation contributed toward an exceptional preparation of root canals compared to hand instrumentation. Elimination of the smear layer enhanced the resistance to microleakage; thermoplasticized gutta percha obturation technique produced a better seal compared to the lateral condensation technique. PMID- 27382542 TI - Retention of denture bases fabricated by three different processing techniques - An in vivo study. AB - AIM: Distortion due to Polymerization shrinkage compromises the retention. To evaluate the amount of retention of denture bases fabricated by conventional, anchorized, and injection molding polymerization techniques. MATERIALS AND METHODS: Ten completely edentulous patients were selected, impressions were made, and master cast obtained was duplicated to fabricate denture bases by three polymerization techniques. Loop was attached to the finished denture bases to estimate the force required to dislodge them by retention apparatus. Readings were subjected to nonparametric Friedman two-way analysis of variance followed by Bonferroni correction methods and Wilcoxon matched-pairs signed-ranks test. RESULTS: Denture bases fabricated by injection molding (3740 g), anchorized techniques (2913 g) recorded greater retention values than conventional technique (2468 g). Significant difference was seen between these techniques. CONCLUSIONS: Denture bases obtained by injection molding polymerization technique exhibited maximum retention, followed by anchorized technique, and least retention was seen in conventional molding technique. PMID- 27382543 TI - A randomized clinical study for comparative evaluation of Aloe Vera and 0.2% chlorhexidine gluconate mouthwash efficacy on de-novo plaque formation. AB - OBJECTIVE: To comparatively assess the antiplaque efficacy of Aloe vera mouthwash and 0.2% chlorhexidine gluconate mouthwash on de novo plaque formation. MATERIALS AND METHODS: This was a randomized, single blind, parallel, controlled clinical study with 90 healthy participants, with mean age of 27.19 +/- 12.08 years. After thorough oral prophylaxis, participants were instructed to discontinue mechanical plaque control. Participants were divided randomly into three groups; pure Aloe vera mouthwash was dispensed to the test group; control group received 0.2% chlorhexidine gluconate mouthwash; in Placebo group, flavored distilled water was used as oral rinse twice daily. Effect on 4-day de novo plaque formation was assessed by comparing pre-rinsing Quigley Hein Modified Plaque Scores were analyzed statistically using analysis of variance and Student's t-test. RESULTS: Post-rinsing control group showed the least plaque score which was comparable to the test group. Both the control group and test group showed significant difference with the placebo group. CONCLUSIONS: Herbal mouthwash containing Aloe vera mouthwash has comparable antiplaque efficacy as the gold standard 0.2% chlorhexidine gluconate with fewer side effects and can be considered as an alternative. PMID- 27382544 TI - Evaluation of anticardiolipin antibodies in tobacco users and non-tobacco users with severe chronic periodontal disease. AB - AIMS: Many studies have proven that b2-glycoprotein-I-dependent anticardiolipin is elevated in periodontal diseases. Systemic lupus erythematosus and antiphospholipid syndrome, which are usually associated with high antiphospholipid antibodies, are more prone to adverse pregnancy outcomes and cardiovascular sequelae. Therefore, the aim of the present study is to evaluate IgG, IgM anticardiolipin antibodies in tobacco users and non-tobacco users with severe chronic periodontal disease. MATERIALS AND METHODS: Based on the Armitage classification, 2000, 40 severe periodontitis (group D) (mean clinical attachment loss greater than 2.5 mm) male patients were selected for the study with the age range of 35-65 years and good general health from the Department of periodontics, SRM Kattankulathur Dental College, Chennai. They were classified as smokers (20 subjects) and non-smokers (20 subjects). Blood samples were collected and IgG, IgM antibodies were semi-quantitatively analyzed by enzyme-linked immunosorbent assay. The data thus collected were statistically analyzed by independent student's t-test. RESULTS: Results showed that smokers with severe periodontitis exhibited marked increase in anticardiolipin IgG, IgM compared to non-smokers. They showed a positive correlation and statistical significance (P < 0.0001) between mean clinical attachment loss and IgG and IgM values. CONCLUSIONS: Results showed a rise in anticardiolipin antibodies in smokers with severe periodontitis, which indicates that these patients are more prone to coronary heart disease. PMID- 27382545 TI - Cancellous osteoma of maxilla: A rare case report. AB - Osteoma is a slow growing benign tumor result from either cancellous or compact bone proliferation. Osteoma of the jaws may arise from the surface of the bone as a sessile mass located either peripherally or endosteally. This paper presents a rare case report of peripheral cancellous osteoma, involving the buccal cortical plate and alveolar process of the right maxilla of a 37-year-old female patient. PMID- 27382546 TI - Effects of vildagliptin as add-on treatment in patients with type 2 diabetes mellitus: insights from long-term clinical studies in Japan. AB - BACKGROUND: Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is wildly used to treat type 2 diabetes mellitus (T2DM) with mono- or combination-therapy. We review two previously published open-label studies to extract insights on the long-term efficacy and safety of vildagliptin. METHODS: Two studies were conducted in Japan to assess the efficacy and safety of vildagliptin as an add-on to other oral antidiabetes drugs (OADs) for 52 weeks. These studies were performed under the similar protocol in Japanese patients with T2DM who were inadequately controlled with OAD monotherapy [excluding other dipeptidyl peptidase-4 (DPP-4) inhibitors]. RESULTS: Addition of vildagliptin (50 mg twice daily) to other OAD monotherapy [sulfonylurea (SU), metformin, thiazolidinedione, alpha-glucosidase inhibitor and glinide] reduced glycated hemoglobin (HbA1c) levels by -0.64 %,-0.75 %,-0.92 %,-0.94 % and - 0.64 %, respectively, over 52 weeks of treatment. Overall, the incidence of hypoglycemia was low and was slightly higher in the add-on to SU treatment group compared with the other groups. The incidences of adverse events were comparable among the treatment groups, and vildagliptin was well-tolerated as add-on therapy to other OADs. CONCLUSIONS: The evidence from the two studies indicates that vildagliptin as an add-on therapy to other OADs is a clinically reasonable option for Japanese patients with T2DM who respond inadequately to other OAD monotherapy. PMID- 27382547 TI - Diagnosis and treatment of autoimmune hemolytic anemia: classic approach and recent advances. PMID- 27382548 TI - Korea Blood Cancer Association: for supporting the patients suffering from blood cancers. PMID- 27382549 TI - Dysplastic eosinophils in myelodysplastic syndrome: association with complex karyotypes. PMID- 27382550 TI - Hansen's fingerprints in bone marrow histiocytes. PMID- 27382551 TI - Dabigatran approaching the realm of heparin-induced thrombocytopenia. AB - Heparin-induced thrombocytopenia (HIT) is a serious, immune mediated complication of exposure to unfractionated or low-molecular-weight heparin. Though rare, it is a condition associated with high morbidity and mortality that requires immediate change to alternative anticoagulants for the prevention of life-threatening thrombosis. The direct thrombin inhibitors lepirudin and argatroban are currently licensed for the treatment of HIT. Dabigatran, a novel oral anticoagulant (NOAC) with a similar mechanism of action and effective use in other indications, has recently been proposed as another therapeutic option in cases of HIT. This review serves as an introduction to using dabigatran for this purpose, detailing the clinical aspects of its administration, evidence of its performance compared to other anticoagulants, and the preliminary reports of HIT successfully treated with dabigatran. As the literature on this develops, it will need to include clinical trials that directly evaluate dabigatran against the other NOACs and current treatment options. PMID- 27382552 TI - Clinical characteristics and treatment outcomes of primary autoimmune hemolytic anemia: a single center study from South India. AB - BACKGROUND: Autoimmune hemolytic anemia (AIHA) is a less recognized, potentially fatal condition. There is a scarcity of data on clinicoserological characteristics and response to therapy concerning this disease from South India. METHODS: Data for 33 patients with primary AIHA recorded from July 2009 to June 2015 were retrospectively analyzed for clinical presentation, response to frontline therapy, durability of response, time to next treatment (TTNT), and response to second-line agents. RESULTS: The median follow-up period was 50 months. Among 33 patients, 48% of the cases were warm autoimmune hemolytic anemia (WAIHA), 46% were cold agglutinin disease (CAD), and 6% were atypical. Three fourth of patients had severe anemia (<8 g/dL hemoglobin [Hb]) at onset; younger patients (age <40 yr) had more severe anemia. All of the patients who required treatment received oral prednisolone at 1.5 mg/kg/d as a frontline therapy, and the response rate was 90% (62% complete response [CR] and 28% partial response [PR]). The overall response to corticosteroids in WAIHA and CAD was 87% and 92%, respectively. The median corticosteroid duration was 14 months, and 50% of the patients required second-line agents. Fourteen patients received azathioprine as a second-line agent, and 11 of these patients responded well, with half of them not requiring a third agent. Four patients developed severe infections (pneumonia, sepsis, and soft tissue abscess) and two had life-threatening venous thrombosis. One case of death was recorded. CONCLUSION: AIHA is a heterogeneous disease that requires care by physicians experienced in treating these patients. PMID- 27382553 TI - Platelet count recovery after intravenous immunoglobulin predicts a favorable outcome in children with immune thrombocytopenia. AB - BACKGROUND: Childhood immune thrombocytopenic purpura (ITP) is a common acquired bleeding disorder. Even though most children recover, either spontaneously or with therapy, 10-20% of newly diagnosed ITP cases have a chronic course beyond 12 months. This study evaluated whether clinical and laboratory findings can predict the response to intravenous immunoglobulin (IVIG) and progression to persistent or chronic ITP in children. METHODS: During the period between March 2003 and June 2015, we retrospectively analyzed 72 children, newly diagnosed with ITP, who received IVIG treatment. Peripheral blood counts were obtained at diagnosis and at 1, 3, 6, and 12 months after IVIG treatment. RESULTS: After 6 months of IVIG treatment, 14 of 72 patients (19.4%) had persistent ITP, and after 12 months, 7 of 40 patients (17.5%) had chronic ITP. Age at diagnosis, gender, history of viral infection, or vaccination before disease onset were not statistically correlated with platelet recovery at 6 and 12 months. However, a platelet count recovery of >=100*10(3)/uL at 1 and 3 months was significantly correlated with platelet recovery at 6 (P<0.001 and P<0.001, respectively) and 12 (P=0.007 and P=0.004, respectively) months. CONCLUSION: This study demonstrated that early platelet count recovery, at 1 and 3 months after IVIG treatment, predicts a short disease duration and a favorable outcome in children with newly diagnosed ITP. Further investigation in a larger group of patients is warranted to validate these findings. PMID- 27382554 TI - Risk factors for mortality in patients with bloodstream infections during the pre engraftment period after hematopoietic stem cell transplantation. AB - BACKGROUND: Bloodstream infections (BSI) remain a frequent complication during the pre-engraftment period after hematopoietic stem cell transplantation (HSCT), resulting in high mortality rates. This study evaluated risk factors for mortality in hematopoietic stem cell transplant recipients with BSI in the pre engraftment period. METHODS: This prospective case control study was performed at the Center of Hematology and Bone Marrow Transplantation in Minsk, Republic of Belarus. Data relating to patient age and gender, date and type of transplantation, conditioning chemotherapy regimen, microorganisms isolated from blood, and antibacterial therapy were prospectively collected from all hematopoietic stem cell recipients with microbiologically proven cases of BSI in the pre-engraftment period. The primary outcome was all-cause 30-day mortality after onset of febrile neutropenia. RESULTS: A total of 135 adult patients with microbiologically proven BSI after HSCT were studied, with 65.2% of cases caused by gram-negative microorganisms and 21.5% by non-fermenting bacteria. Inadequate empiric antibacterial therapy and isolation of carbapenem-resistant non fermenting gram-negative bacteria (Acinetobacter baumannii and Pseudomonas aeruginosa) were independently associated with increased all-cause 30-day mortality in these patients. CONCLUSION: The risk factors for mortality in adult patients with BSI in the pre-engraftment period after HSCT were inadequacy of empirical antibacterial therapy and isolation of carbapenem-resistant A. baumannii or P. aeruginosa. PMID- 27382555 TI - Unrelated hematopoietic stem cell registry and the role of the Hematopoietic Stem Cell Bank. AB - BACKGROUND: The hematopoietic stem cell bank has been actively recruiting registrants since 1994. This study systematically reviews its operations and outcomes over the last 20 years. METHODS: Retrospective data on a total of 47,711 registrants were reviewed. Relevant data were processed using PASW Statistics for Windows, version 18.0. RESULTS: As of 2013, the Korean Network for Organ Sharing database contained 265,307 registrants. Of these, 49,037 (18%) registrants committed to hematopoietic cell donation from 1994 to 2013. Fifty-seven percent of the registrants were men, and 43% were women. The reasons for opting out of the registry included refusal to donate (70%), family refusal (28%), and others (2%). The donation willingness of registrants was significantly higher than those who refused to receive a mail to confirm their continued enrollment (chi(2)=6.103, P=0.013). The bank successfully coordinated a total of 512 donors among newly matched donors from 1995 to 2013, of which the bone marrow and peripheral blood stem cell accounted for 40.8% and 59.2% of the total donations, respectively. CONCLUSION: Our recruitment activities focus on promoting voluntary registration and the importance of updating personal contact information. We expect that these data may be useful for diverse studies and demonstrate the positive impacts on the donation program. PMID- 27382556 TI - Baseline renal function as a prognostic indicator in patients with newly diagnosed diffuse large B-cell lymphoma. AB - BACKGROUND: The association between baseline renal impairment (RI) and the prognosis of diffuse large B-cell lymphoma (DLBCL) was previously not defined. The aim of this study was to evaluate the prognostic value of RI in patients with DLBCL treated with three-weekly rituximab plus cyclophosphamide, Adriamycin, vincristine, and prednisolone immunochemotherapy (R-CHOP21). METHODS: Patients with newly diagnosed de novo DLBCLs treated with >=1 cycle of R-CHOP21 were analyzed retrospectively. Pretreatment blood samples were collected and the glomerular filtration rate (GFR) was calculated. RI was defined by a GFR of <60 mL/min/1.73 m(2) according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. RESULTS: Of the 185 patients enrolled in the present study, 19 patients (10.3%) had RI. The reasons for baseline RI were pre existing CKD (N=5), acute kidney injury due to either obstruction (N=2) or electrolyte imbalance (N=2) related to DLBCL, and undefined causes (N=10). Patients with baseline RI showed inferior overall survival (OS) compared to those without RI (P<0.001). In multivariate analysis, RI was identified as an International Prognostic Index (IPI)-independent prognostic indicator. A baseline hemoglobin level of <10 g/dL and the presence of RI effectively discriminated a portion of the patients with far inferior event-free survival and OS among the patients having high or high-intermediate risk cancers according to either the standard- or the National Comprehensive Cancer Network-IPI. CONCLUSION: Pretreatment RI was an independent prognostic marker for inferior OS in patients with DLBCL treated with R-CHOP21 immunochemotherapy. PMID- 27382557 TI - A retrospective analysis of cytogenetic alterations in patients with newly diagnosed multiple myeloma: a single center study in Korea. AB - BACKGROUND: The accurate identification of cytogenetic abnormalities in multiple myeloma (MM) has become more important over recent years for the development of new diagnostic and prognostic markers. In this study, we retrospectively analyzed the cytogenetic aberrations in MM cases as an initial assessment in a single institute. METHODS: We reviewed the cytogenetic results from 222 patients who were newly diagnosed with MM between January 2000 and December 2015. Chromosomal analysis was performed on cultured bone marrow samples by standard G-banding technique. At least 20 metaphase cells were analyzed for karyotyping. RESULTS: Clonal chromosome abnormalities were detected in 45.0% (100/222) of the patients. Among these results, 80 cases (80.0%) had both numerical and structural chromosome abnormalities. Overall hyperdiploidy with structural cytogenetic aberrations was the most common finding (44.0%), followed by hypodiploidy with structural aberrations (28.0%). Amplification of the long arm of chromosome 1 and -13/del(13q) were the most frequent recurrent abnormalities, and were detected in 50 patients (50.0%) and 40 patients (40.0%) with clonal abnormalities, respectively. The most common abnormality involving 14q32 was t(11;14)(q13;q32), which was observed in 19 cases. CONCLUSION: These findings demonstrate that myeloma cells exhibit complex aberrations regardless of ploidy, even from a single center in Korea. Conventional cytogenetic analysis should be included in the initial diagnostic work-up for patients suspected of having MM. PMID- 27382558 TI - Prognostic relevance of the Ki-67 proliferation index in patients with mantle cell lymphoma. AB - BACKGROUND: A high Ki-67 proliferation index (PI) in neoplastic cells is associated with poor survival in mantle cell lymphoma (MCL). We aimed to determine the cut-off values for the Ki-67 PI as a prognostic factor in MCL according to bone marrow findings. METHODS: Immunohistochemical (IHC) staining for Ki-67 was performed on formalin-fixed paraffin-embedded biopsy tissues from 56 patients with MCL. Patients were grouped based on their Ki-67 PI values. Survival analyses were carried out and the cut-off value for the Ki-67 PI was determined. RESULTS: Of the 56 patients, 39 (69.6%) showed bone marrow involvement of MCL; 21 of these patients had leukemic manifestations at the time of diagnosis. The results of the Ki-67 IHC staining were as follows: <=10% in 22 patients, 11-20% in 14 patients, 21-30% in 3 patients, 31-40% in 4 patients, 41 50% in 4 patients, and >50% in 9 patients. A cut-off value of 20% revealed significantly different survival rates with mean survival times of 69.8 months (Ki-67 PI<=20%) and 47.9 months (Ki-67 PI>20%), irrespective of bone marrow findings (P=0.034). Clinical outcomes did not differ, regardless of bone marrow findings. However, in cases with bone marrow involvement, the Ki-67 cut-off value of 30% for overall survival was required to yield statistical significance (P=0.033). CONCLUSION: The 20% cut-off value for the Ki-67 PI was clinically meaningful, regardless of bone marrow involvement of MCL. For patients with bone marrow involvement, the statistically significant cut-off value increased to 30%. PMID- 27382559 TI - Acute myeloid leukemia with t(4;12)(q12;p13): report of 2 cases. PMID- 27382560 TI - Primary acquired chronic pure red cell aplasia refractory to standard treatments: remission with rituximab. PMID- 27382561 TI - Successful treatment of angioimmunoblastic T-cell lymphoma with clarithromycin. PMID- 27382562 TI - Bilateral myelomatous pleural effusion: presentation of two cases. PMID- 27382563 TI - A rare case of diffuse large B cell lymphoma-associated hemophagocytic syndrome initially present in the bone marrow with a favorable clinical course. PMID- 27382564 TI - Long-Term Fracture Resistance of Simulated Immature Teeth Filled with Various Calcium Silicate-Based Materials. AB - Objective. The aim of this in vitro study was to evaluate the long-term fracture resistance of simulated human immature permanent teeth filled with BioAggregateTM (BA), mineral trioxide aggregate (MTA), and EndoSequence(r) Root Repair Material (ERRM). Material and Methods. 40 teeth, simulated to average root length of 13 +/ 1 mm (Cvek's stage 3), were included in the study. The teeth were randomly divided into four groups: Group 1: DiaRoot(r) BA, Group 2: MTA-PlusTM (MTA-P), Group 3: MTA-Angelus (MTA-A), and Group 4: ERRM. The root canal filling materials were applied according to the manufacturers' instructions. After 24 months of incubation, the roots of the teeth were embedded in acrylic blocks and subjected to fracture testing. The resultant data were analyzed statistically by Kruskal Wallis and Mann-Whitney U tests. Results. Mean (+/-SD) failure loads (MPa) were 20.46 +/- 2.53 for BA, 18.88 +/- 5.13 for MTA-P, 14.12 +/- 1.99 for MTA-A, and 17.65 +/- 4.28 for ERRM groups. BA group exhibited the highest and MTA-A group showed the lowest resistance to fracture. Significant differences in fracture resistance were found between the groups of BA and MTA-A (p < 0.001), MTA-P and MTA-A (p < 0.05), and ERRM and MTA-A (p < 0.05). Conclusion. Within the limitations of this study, data suggests that BA-filled immature teeth demonstrate higher fracture resistance than other groups at 24 months appearing to be the most promising material tested. PMID- 27382565 TI - Comparative Analysis of Human B Cell Epitopes Based on BCG Genomes. AB - Background. Tuberculosis is a huge global health problem. BCG is the only vaccine used for about 100 years against TB, but the reasons for protection variability in populations remain unclear. To improve BCG efficacy and develop a strategy for new vaccines, the underlying genetic differences among BCG subtypes should be understood urgently. Methods and Findings. Human B cell epitope data were collected from the Immune Epitope Database. Epitope sequences were mapped with those of 15 genomes, including 13 BCGs, M. bovis AF2122/97, and M. tuberculosis H37Rv, to identify epitopes distribution. Among 398 experimentally verified B cell epitopes, 321 (80.7%) were conserved, while the remaining 77 (19.3%) were lost to varying degrees in BCGs. The variable protective efficacy of BCGs may result from the degree of B cell epitopes deficiency. Conclusions. Here we firstly analyzed the genetic characteristics of BCGs based on B cell epitopes and found that B cell epitopes distribution may contribute to vaccine efficacy. Restoration of important antigens or effective B cell epitopes in BCG could be a useful strategy for vaccine development. PMID- 27382567 TI - Computer-Aided Diagnosis of Micro-Malignant Melanoma Lesions Applying Support Vector Machines. AB - Background. One of the fatal disorders causing death is malignant melanoma, the deadliest form of skin cancer. The aim of the modern dermatology is the early detection of skin cancer, which usually results in reducing the mortality rate and less extensive treatment. This paper presents a study on classification of melanoma in the early stage of development using SVMs as a useful technique for data classification. Method. In this paper an automatic algorithm for the classification of melanomas in their early stage, with a diameter under 5 mm, has been presented. The system contains the following steps: image enhancement, lesion segmentation, feature calculation and selection, and classification stage using SVMs. Results. The algorithm has been tested on 200 images including 70 melanomas and 130 benign lesions. The SVM classifier achieved sensitivity of 90% and specificity of 96%. The results indicate that the proposed approach captured most of the malignant cases and could provide reliable information for effective skin mole examination. Conclusions. Micro-melanomas due to the small size and low advancement of development create enormous difficulties during the diagnosis even for experts. The use of advanced equipment and sophisticated computer systems can help in the early diagnosis of skin lesions. PMID- 27382566 TI - Inflammatory Cardiomyopathy: A Current View on the Pathophysiology, Diagnosis, and Treatment. AB - Inflammatory cardiomyopathy is defined as inflammation of the heart muscle associated with impaired function of the myocardium. In our region, its etiology is most often viral. Viral infection is a possible trigger of immune and autoimmune mechanisms which contributed to the damage of myocardial function. Myocarditis is considered the most common cause of dilated cardiomyopathy. Typical manifestation of this disease is heart failure, chest pain, or arrhythmias. The most important noninvasive diagnostic method is magnetic resonance imaging, but the gold standard of diagnostics is invasive examination, endomyocardial biopsy. In a significant proportion of cases with impaired left ventricular systolic function, recovery occurs spontaneously in several weeks and therefore it is appropriate to postpone critical therapeutic decisions about 3-6 months after start of the treatment. Therapy is based on standard heart failure treatment; immunosuppressive or antimicrobial treatment may be considered in some cases depending on the results of endomyocardial biopsy. If severe dysfunction of the left ventricle persists, device therapy may be needed. PMID- 27382568 TI - Effects of Acute and Chronic Heavy Metal (Cu, Cd, and Zn) Exposure on Sea Cucumbers (Apostichopus japonicus). AB - Acute and chronic toxicity tests were conducted with sea cucumber (Apostichopus japonicus) exposed to heavy metals. Acute toxicity values (96 h LC50) were 2.697, 0.133, and 1.574 mg L(-1) for Zn, Cu, and Cd, respectively, and were ranked in order of toxicity: Cu > Cd > Zn. Under chronic metal exposure the specific growth rates of sea cucumbers decreased with the increase of metal concentration for all the three metals. After acute metal exposure, the oxygen consumption rate (OCR) decreased. The OCRs in all groups were significantly different than control (P < 0.05) except in the group treated with 1.00 mg L(-1) Zn (P < 0.05), where the increase of OCR was observed. The OCRs in groups chronically exposed to metals were significantly lower than that in the control group (P < 0.05). The activity of both pyruvate kinase (PK) and hexokinase (HK) in sea cucumbers followed: respiratory tree > muscle > intestine in natural sea water. After chronic Zn, Cu, and Cd exposure, the change pattern of HK and PK in respiratory tree, muscle, and intestine varied slightly. However, the activity of the enzyme showed a general trend of increase and then decrease and the higher the exposure concentration was, the earlier the highest point of enzyme activity was obtained. PMID- 27382569 TI - Effect of Surface Treatment on Shear Bond Strength between Resin Cement and Ce TZP/Al2O3. AB - Purpose. Although several studies evaluating the mechanical properties of Ce TZP/Al2O3 have been published, to date, no study has been published investigating the bonding protocol between Ce-TZP/Al2O3 and resin cement. The aim of this study was to evaluate the shear bond strength to air-abraded Ce-TZP/Al2O3 when primers and two different cement types were used. Materials and Methods. Two types of zirconia (Y-TZP and Ce-TZP/Al2O3) specimens were further divided into four subgroups according to primer application and the cement used. Shear bond strength was measured after water storage for 3 days or 5,000 times thermocycling for artificial aging. Results. The Y-TZP block showed significantly higher shear bond strength than the Ce-TZP/Al2O3 block generally. Primer application promoted high bond strength and less effect on bond strength reduction after thermocycling, regardless of the type of cement, zirconia block, or aging time. Conclusions. Depending on the type of the primer or resin cement used after air abrasion, different wettability of the zirconia surface can be observed. Application of primer affected the values of shear bond strength after the thermocycling procedure. In the case of using the same bonding protocol, Y-TZP could obtain significantly higher bond strength compared with Ce-TZP/Al2O3. PMID- 27382570 TI - A Comparison of the Effects of Neuronal Nitric Oxide Synthase and Inducible Nitric Oxide Synthase Inhibition on Cartilage Damage. AB - The objective of this study was to investigate the effects of selective inducible nitric oxide synthase and neuronal nitric oxide synthase inhibitors on cartilage regeneration. The study involved 27 Wistar rats that were divided into five groups. On Day 1, both knees of 3 rats were resected and placed in a formalin solution as a control group. The remaining 24 rats were separated into 4 groups, and their right knees were surgically damaged. Depending on the groups, the rats were injected with intra-articular normal saline solution, neuronal nitric oxide synthase inhibitor 7-nitroindazole (50 mg/kg), inducible nitric oxide synthase inhibitor amino-guanidine (30 mg/kg), or nitric oxide precursor L-arginine (200 mg/kg). After 21 days, the right and left knees of the rats were resected and placed in formalin solution. The samples were histopathologically examined by a blinded evaluator and scored on 8 parameters. Although selective neuronal nitric oxide synthase inhibition exhibited significant (P = 0.044) positive effects on cartilage regeneration following cartilage damage, it was determined that inducible nitric oxide synthase inhibition had no statistically significant effect on cartilage regeneration. It was observed that the nitric oxide synthase activation triggered advanced arthrosis symptoms, such as osteophyte formation. The fact that selective neuronal nitric oxide synthase inhibitors were observed to have mitigating effects on the severity of the damage may, in the future, influence the development of new agents to be used in the treatment of cartilage disorders. PMID- 27382571 TI - Epidemiology and Outcome of Ventilator-Associated Pneumonia in a Heterogeneous ICU Population in Qatar. AB - Objective. The purpose of this study is to collect data on epidemiology, microbiology, and outcome of VAP in our ICUs for reevaluation of the therapeutic strategies. Methods. This retrospective study involved all adult patients, 15 years of age or older, diagnosed with VAP in multidisciplinary ICUs at Hamad General Hospital between January 2010 and December 2012. Results. A total of 106 patients were enrolled. The mean incidence of VAP was 5.0 per 1000 ventilator days. It was predominant among younger age group (<60 years), male patients (80.2%), and trauma ICU admissions (49.0%). The most common comorbidity was hypertension (34%) and polytrauma (36.8%) was the most frequent admission diagnosis. 30-day mortality was 23.6% and it was significantly higher in >=60 years age group, female gender, patients with diabetes mellitus, hypertension, chronic respiratory disease, >=1 comorbidity, and poor functional status, smokers, medical and surgical ICU admissions, and patients with previous stay in medical/surgical wards, inappropriate empirical therapy, and admission diagnosis of respiratory failure. Gram-negative bacilli were the most frequent respiratory specimen isolates, Pseudomonas spp. being the most common. Majority of our Acinetobacter isolates were multidrug resistant. Conclusion. The incidence of VAP in our ICUs was low. Higher mortality rates were observed in certain subgroup of patients. Resistance to commonly used antimicrobials is likely to require reevaluation of the therapeutic strategies at our institution. PMID- 27382572 TI - Overweight and General and Abdominal Obesity in a Representative Sample of Spanish Adults: Findings from the ANIBES Study. AB - Objective. To analyze the anthropometric parameters from a representative sample of Spanish adults participating in ANIBES study and the prevalence of general and abdominal obesity. Methods. This cross-sectional study focused on 1655 adults aged 18-64 years. Weight, height, and waist circumference (WC) were evaluated, and body mass index (BMI) and waist to height ratio (WHtR) were calculated. A composite index combining BMI and WHtR was designed to establish five groups with different anthropometric status. Results. The prevalence of overweight (OW) was 35.8% and that of obesity was 19.9%. Obesity (OB) was higher among men (OR 1.725, 1.415-2.104; p = 0.000) and each year of age increased the risk of obesity (OR 1.054, 1.045-1.064; p = 0.000). The prevalence of abdominal obesity (WHtR >= 0.5) was 58.4%. Only 36.1% of the population had an optimal anthropometric situation (BMI < 25 kg/m(2), WHtR < 0.5), whereas 50.1% had weight excess and high WHtR (BMI >= 25 kg/m(2), WHtR >= 0.5). Conclusions. More than half of Spanish population has weight excess and cardiometabolic risk. The results of this study provide an understanding of the current anthropometric situation in the Spanish population, as a first step toward planning interventions and assessing their effectiveness in the future. PMID- 27382573 TI - Sex-Specific Association between Serum Uric Acid and Nonalcoholic Fatty Liver Disease in Type 2 Diabetic Patients. AB - Across-sectional study was performed in 541 type 2 diabetic patients to determine the relationship between serum uric acid (SUA) and NAFLD in type 2 diabetic patients. Clinical parameters including SUA were determined and NAFLD was diagnosed by ultrasonography. SUA was significantly higher in type 2 diabetic subjects with NAFLD than in those without NAFLD in men, but not in women. Furthermore, the prevalence rate of NAFLD increased progressively across the sex specific SUA tertiles only in men (37.9%, 58.6%, and 72.6%, resp., P for trend < 0.001). After adjusting for confounding factors, the odd ratios (95% CI) for NAFLD were 1 (reference), 2.93 (95%CI 1.25-6.88), and 3.93 (95% CI 1.55-9.98), respectively, across the tertiles of SUA in men. Contrastingly, SUA levels in women were not independently associated with the risk of NAFLD. Our data suggests that SUA is specifically associated with NAFLD in male type 2 diabetic subjects, independent of insulin resistance and other metabolic factors. PMID- 27382574 TI - Increasing GLP-1 Circulating Levels by Bariatric Surgery or by GLP-1 Receptor Agonists Therapy: Why Are the Clinical Consequences so Different? AB - The "incretin effect" is used to describe the observation that more insulin is secreted after the oral administration of glucose compared to that after the intravenous administration of the same amount of glucose. During the absorption of meals, the gut is thought to regulate insulin secretion by secreting a specific factor that targets pancreatic beta cells. Additional research confirmed this hypothesis with the discovery of two hormones called incretins: gastric inhibitory peptide (GIP) and glucagon-like peptide 1 (GLP-1). During meals, specific cells in the gut (L and K enteroendocrine cells) secrete incretins, causing an increase in the blood concentrations of, respectively, GLP-1 and GIP. Bariatric surgery is now proposed during the therapeutic management of type 2 diabetes in obese or overweight populations. It has been hypothesized that restoration of endogenous GLP-1 secretion after the surgery may contribute to the postsurgical resolution of diabetes. In 2005, the commercialization of GLP-1 receptor agonists gave the possibility to test this hypothesis. A few years later, it is now accepted that GLP-1 receptor agonists and bariatric surgery differently improve type 2 diabetes. These differences between endogenous and exogenous GLP-1 on glucose homeostasis emphasized the dual properties of GLP-1 as a peptide hormone and as a neurotransmitter. PMID- 27382575 TI - Interaction between Mean Arterial Pressure and HbA1c in Prediction of Cardiovascular Disease Hospitalisation: A Population-Based Case-Control Study. AB - Objective. To explore the relationship between mean arterial pressure (MAP), HbA1c, and cardiovascular (CV) hospitalisation risk in type 2 diabetes. Design. Population-based case-control study. Settings. Primary and secondary care level in Cambridgeshire, United Kingdom. Participants. 588 patients with type 2 diabetes from 18 English general practices recording a CV hospitalisation in 2009 2011 were included. Risk-set sampling was used to select 2920 gender, age, and practice matched control type 2 diabetes patients. Main Outcome Measure. Conditional logistic regression was used to explore further dose-response relationships between MAP, HbA1c, and CV hospitalisation risk. Results. The relationship between MAP and CV hospitalisation was nonlinear (P < 0.001 for linearity test). The MAP associated with the lowest CV hospitalisation risk was 97 (95% CI: 93-101) mmHg. An interaction between MAP and HbA1c for increased risk of cardiovascular hospitalisation was observed among those with HbA1c < 7% (53 mmol/mol) and MAP < 97 mmHg. Conclusions. In type 2 diabetes, MAP is a good predictor of CV hospitalisation risk. CV hospitalisation is lowest with a MAP between 93 and 101 mmHg. CV hospitalisation was particularly high among those with both a low MAP and a lower HbA1c. PMID- 27382576 TI - New Alternatives for Autoimmune Disease Treatments: Physicochemical and Clinical Comparability of Biosimilar Etanercept. AB - Etanercept is a recombinant fusion protein approved for the treatment of TNF alpha mediated diseases such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, and ankylosing spondylitis. Herein, we present an evaluation of the physicochemical and biological properties of a biosimilar etanercept and its reference product followed by a clinical study in patients diagnosed with RA intended to demonstrate comparability of their immunomodulatory activity. Identity analyses showed a total correspondence of the primary and higher-order structure between the two products. In regard to intrinsic heterogeneity, both products showed to be highly heterogenous; however the biosimilar etanercept exhibited similar charge and glycan heterogeneity intervals compared to the reference product. Apoptosis inhibition assay also showed that, despite the high degree of heterogeneity exhibited by both products, no significant differences exist in their in vitro activity. Finally, the clinical assessment conducted in RA-diagnosed patients did not show significant differences in the evaluated pharmacodynamic markers of both products. Collectively, the results from the comparability exercise provide convincing evidence that the evaluated biosimilar etanercept can be considered an effective alternative for the treatment of RA. PMID- 27382577 TI - Interprofessional education in the integrated medical education and health care system: A content analysis. AB - INTRODUCTION: The current literature supports the inclusion of inter-professional education in healthcare education. Changes in the structure and nature of the integrated medical education and healthcare system provide some opportunities for interprofessional education among various professions. This study is an attempt to determine the perceptions of students and faculty members about interprofessional education in the context of the medical education and healthcare system. METHODS: This qualitative content analysis study was conducted using purposeful sampling in 2012. Thirteen semi-structured interviews were conducted with 6 faculty members and 7 students at Tehran and Iran Universities of Medical Sciences. Data collection and analysis were concurrent. RESULTS: Data analysis revealed four categories and nine subcategories. The categories emerging from individual interviews were "educational structure", "mediating factors", "conceptual understanding", and "professional identity". These categories are explained using quotes derived from the data. CONCLUSION: Matching the existing educational context and structure with IPE through removing barriers and planning to prepare the required resources and facilities can solve numerous problems associated with implementation and design of inter-professional training programs in Iran. In this way, promoting the development of a cooperative rather than a competitive learning and working atmosphere should be taken into account. The present findings will assist the managers and policy makers to consider IPE as a useful strategy in the integrated medical education and healthcare system. PMID- 27382578 TI - Barriers to integration of behavioral and social sciences in the general medicine curriculum and recommended strategies to overcome them: A systematic review. AB - INTRODUCTION: The integration of behavioral and social sciences (BSS) into the curriculum of medical students in order to equip them with the necessary knowledge, skills and attitudes is an essential issue, emphasized in many researches. Our aim is to investigate the barriers to integrate BSS into the general medicine curriculum as well as the recommended strategies to overcome such barriers through a systematic review of literature. METHODS: PubMed, ERIC, Scopus, CINAHL, Google Scholar, and OPENGREY were searched for studies on the barriers to integration of BSS into the general medicine curriculum as well as the strategies employed to overcome them until August 28, 2015. RESULTS: Sixteen relevant studies were included and the related domains were categorized as barriers and some strategies were recommended to overcome them. In addition, the quality of the included studies was assessed. CONCLUSION: Despite the prominent role of BSS in the effectiveness of health care, these sciences have not been included in the curriculum of medical students effectively. The identified barriers and the strategies used to overcome them should be considered for all integration programs. Future studies should focus on the process of BSS integration in the medical curricula and should evaluate the efficacy of this integration in more detail. PMID- 27382579 TI - Developing an instrument to measure effective factors on Clinical Learning. AB - INTRODUCTION: Although nursing students spend a large part of their learning period in the clinical environment, clinical learning has not been perceived by its nature yet. To develop an instrument to measure effective factors on clinical learning in nursing students. METHODS: This is a mixed methods study performed in 2 steps. First, the researchers defined "clinical learning" in nursing students through qualitative content analysis and designed items of the questionnaire based on semi-structured individual interviews with nursing students. Then, as the second step, psychometric properties of the questionnaire were evaluated using the face validity, content validity, construct validity, and internal consistency evaluated on 227 students from fourth or higher semesters. All the interviews were recorded and transcribed, and then, they were analyzed using Max Qualitative Data Analysis and all of qualitative data were analyzed using SPSS 14. RESULTS: To do the study, we constructed the preliminary questionnaire containing 102 expressions. After determination of face and content validities by qualitative and quantitative approaches, the expressions of the questionnaire were reduced to 45. To determine the construct validity, exploratory factor analysis was applied. The results indicated that the maximum variance percentage (40.55%) was defined by the first 3 factors while the rest of the total variance percentage (59.45%) was determined by the other 42 factors. Results of exploratory factor analysis of this questionnaire indicated the presence of 3 instructor-staff, students, and educational related factors. Finally, 41 expressions were kept in 3 factor groups. The alpha-Cronbach coefficient (0.93) confirmed the high internal consistency of the questionnaire. CONCLUSION: Results indicated that the prepared questionnaire was an efficient instrument in the study of the effective factors on clinical learning as viewed by nursing students since it involves 41 expressions and properties such as instrument design based on perception and experiences of the nursing students about effective factors on clinical learning, definition of facilitator and preventive factors of the clinical learning, simple scoring, suitable validity and reliability, and applicability in different occasions. PMID- 27382580 TI - The influence of parenting style on academic achievement and career path. AB - INTRODUCTION: Several factors affect the academic performance of college students and parenting style is one significant factor. The current study has been done with the purpose of investigating the relationship between parenting styles, academic achievement and career path of students at Shiraz University of Medical Sciences. METHODS: This is a correlation study carried out at Shiraz University of Medical Sciences. Among 1600 students, 310 students were selected randomly as the sample. Baumrind's Parenting Style and Moqimi's Career Path questionnaires were used and the obtained scores were correlated with the students' transcripts. To study the relation between variables Pearson correlation coefficient was used. RESULTS: There was a significant relationship between authoritarian parenting style and educational success (p=0.03). Also findings showed a significant relationship between firm parenting style and Career Path of the students, authoritarian parenting style and Career Path of the students, educational success and Career Path of the students (p=0.001). CONCLUSION: Parents have an important role in identifying children's talent and guiding them. Mutual understanding and close relationship between parents and children are recommended. Therefore, it is recommended that the methods of correct interaction of parents and children be more valued and parents familiarize their children with roles of businesses in society and the need for employment in legitimate businesses and this important affair should be more emphasized through mass media and family training classes. PMID- 27382581 TI - Effects of structured written feedback by cards on medical students' performance at Mini Clinical Evaluation Exercise (Mini-CEX) in an outpatient clinic. AB - INTRODUCTION: Feedback cards are recommended as a feasible tool for structured written feedback delivery in clinical education while effectiveness of this tool on the medical students' performance is still questionable. The purpose of this study was to compare the effects of structured written feedback by cards as well as verbal feedback versus verbal feedback alone on the clinical performance of medical students at the Mini Clinical Evaluation Exercise (Mini-CEX) test in an outpatient clinic. METHODS: This is a quasi-experimental study with pre- and post test comprising four groups in two terms of medical students' externship. The students' performance was assessed through the Mini-Clinical Evaluation Exercise (Mini-CEX) as a clinical performance evaluation tool. Structured written feedbacks were given to two experimental groups by designed feedback cards as well as verbal feedback, while in the two control groups feedback was delivered verbally as a routine approach in clinical education. RESULTS: By consecutive sampling method, 62 externship students were enrolled in this study and seven students were excluded from the final analysis due to their absence for three days. According to the ANOVA analysis and Post Hoc Tukey test, no statistically significant difference was observed among the four groups at the pre-test, whereas a statistically significant difference was observed between the experimental and control groups at the post-test (F = 4.023, p =0.012). The effect size of the structured written feedbacks on clinical performance was 0.19. CONCLUSION: Structured written feedback by cards could improve the performance of medical students in a statistical sense. Further studies must be conducted in other clinical courses with longer durations. PMID- 27382582 TI - Knowledge of triage in the senior medical students in Shiraz University of Medical Sciences. AB - INTRODUCTION: Triage is a response to the problem of overcrowding in Emergency Departments (EDs) and accuracy of decisions made by the triage unit affects the ultimate outcome of EDs. This study was conducted to evaluate the knowledge of triage among last year medical students in Shiraz University of Medical Sciences. METHODS: This is a cross-sectional analytical study whose subjects were all the senior students of medicine (62) in the last year of medicine from January to June 2013 who attended emergency medicine course in the screen room of 2 University Hospitals. This questionnaire was designed in 3 sections including personal data, 15 questions on knowledge of triage and 10 case scenarios for triage decision making and completed by the students. Statistical analysis was performed in SPSS statistical software (version 14) using independent sample t test, one way ANOVA, and Pearson correlation coefficient (p<=0.001). RESULTS: The total mean score of the participants was 10.6+/-1.5, ranging from 7 to 13. 58(93.5%) students had poor triage knowledge. In the scenario's section, the percentage of correct triage by students was 49.2% and those of over and under triage were 28.1% and 22.7%, respectively. There was a significant relationship between the triage accuracy and level of triage (ESI 4) (p<=0.001). CONCLUSION: The level of knowledge of triage in the last year medical students was poor, although most of them had passed a course in the screen room. It is recommended that medical students' educational courses should include sections on the knowledge of triage in emergency rooms. PMID- 27382583 TI - Impact of utilisation of uncompleted handouts on power point presentations (PPT) in rural Indian medical institute. AB - INTRODUCTION: Note taking while attending a PPT requires high activity of memory and writing process which ultimately leads to what is called "death by power point" referring to boredom and fatigue. To overcome this we planned to evaluate the impact of utilisation of uncompleted handouts given prior to PPT presentations. METHODS: Final year MBBS students were divided in 2 batches, batch A and batch B. For a set of lectures one batch was provided with handouts before lecture while the other batch was given lectures only. Crossover was done to avoid bias, all the lectures being given by the same presenter. At the end of each lecture, a short questionnaire of 10 Multiple Choice Question (MCQ) was provided to the students. Mean scores were calculated for lectures with handouts and without handouts. RESULTS: For a set of lectures, when batch A was provided with handouts, the mean score was 28.2; for batch B to which no handouts were given the mean score was 23.4. Similarly, for batch B when provided with handouts the mean score was 29.1, for batch A which was not provided with handouts the mean score was 24. There was an average increase of 4.2 marks. Actual gain when handouts were provided was 1.2 marks per lecture. It was more for the batch comprising of repeater students as compared to the batch of fresher students. Increase in attendance was also noted. CONCLUSION: Providing uncompleted handouts before a didactic lecture definitely results in increase in knowledge gain; repeater students benefit more with uncompleted handouts. PMID- 27382584 TI - There's education, and then there's education in medicine. AB - INTRODUCTION: For some time now the field of medical education has been criticized by many of its stakeholders. Countless debates have been presented in the literature regarding the quality of medical education research, adequacy of methodological rigor, and other concerns. METHODS: At present, the views expressed have largely come from physicians and individuals with less familiarity with education science. RESULTS: As prolific educational researchers with Ph.Ds in Education and Psychology, we offer a critique of medical education's apparent identity crisis and address what we believe are some of the most significant problems continuing to impede the field of medical education from catching up with the broader field of education. We close with specific recommendations for improving the overall state of medical education. CONCLUSION: Finally, both editors and reviewers for medical education journals need to abandon the hegemonic views regarding research design. Thus, research designs that many in the clinical sciences often perceive as 'weak' are entirely appropriate in education research fields. PMID- 27382585 TI - Online Social Support for Patients with Multiple Sclerosis: A Thematic Analysis of Messages Posted to a Virtual Support Community. AB - BACKGROUND: Currently with the emergence of the Internet, patients have an opportunity to exchange social support online. However, little attention has been devoted to different dimensions of online social support exchanged in virtual support communities for patients with multiple sclerosis (MS). METHODS: To provide a rich insight, the aim of this qualitative study was to explore and categorize different dimensions of online social support in messages exchanged in a virtual support community for patients with MS. A total of 548 posted messages created during one year period were selected using purposive sampling to consider the maximum variation sampling. Prior-research-driven thematic analysis was then conducted. In this regard, we used the Cutruna and Suhr's coding system. The messages that could not be categorized with the used coding system were thematically analyzed to explore new additional social support themes. RESULTS: The results showed that various forms of social support including informational, emotional, network, esteem and tangible support were exchanged. Moreover, new additional social support themes including sharing personal experiences, sharing coping strategies and spiritual support emerged in this virtual support community. CONCLUSION: The wide range of online social support exchanged in the virtual support community can be regarded as a supplementary source of social support for patients with MS. Future researches can examine online social support more comprehensively considering additional social support themes emerging in the present study. PMID- 27382586 TI - The Nurse-Led Telephone Follow-Up on Medication and Dietary Adherence among Patients after Myocardial Infarction: A Randomized Controlled Clinical Trial. AB - BACKGROUND: Adherence to dietary and medication regimen plays an important role in successful treatment and reduces the negative complications and severity of the disease. Therefore, the present study aimed to investigate the effect of nurse-led telephone follow-up on the level of adherence to dietary and medication regimen among patients after Myocardial Infarction (MI). METHODS: This non blinded randomized controlled clinical trial was conducted on 100 elderly patients with MI who had referred to the cardiovascular clinics in Shiraz. Participants were selected and randomly assigned to intervention and control groups using balanced block randomization method. The intervention group received a nurse-led telephone follow-up. The data were collected using a demographic questionnaire, Morisky's 8-item medication adherence questionnaire, and dietary adherence questionnaire before and three months after the intervention. Data analysis was done by the SPSS statistical software (version 21), using paired t test for intra-group and Chi-square and t-test for between groups comparisons. Significance level was set at<0.05. RESULTS: The results of Chi-square test showed no statistically significant difference between the intervention and control groups with respect to their adherence to dietary and medication regimen before the intervention (P>0.05). However, a statistically significant difference was found between the two groups in this regard after the intervention (P<0.05). The mean differences of dietary and medication adherence scores between pre- and post-tests were significantly different between the two groups. Independent t test showed these differences (P=0.001). CONCLUSION: The results of the present study confirmed the positive effects of nurse-led telephone follow-up as a method of tele-nursing on improvement of adherence to dietary and medication regimen in the patients with MI. TRIAL REGISTRATION NUMBER: IRCT201409148505N8. PMID- 27382587 TI - A Comparison between The Effectiveness of Short Message Service and Reminder Cards Regarding Medication Adherence in Patients with Hypertension: A Randomized Controlled Clinical Trial. AB - BACKGROUND: Hypertension is increasing rapidly in developing countries. Today, modern technologies are suggested as the tools used to enhance medication adherence. This study aimed to compare the effectiveness of short message service (SMS) to reminder cards with regard to medication adherence in patients with hypertension. METHODS: The present study is a randomized controlled clinical trial. The subjects consisted of 123 patients with hypertension at the clinical educational center of Sayyed-Al Shohada, Urmia, who met the study criteria. Selected based on the convenience method, the samples were randomly divided into three groups: the SMS group, the reminder-cards group, and the control group. The subjects in the SMS group were sent 6 text messages a week for three months, and the subjects in the reminder-cards group were trained in how and in what order to use their cards. Hill-Bone medication adherence scale was completed by all the participants before and three months after the intervention. Data analysis was performed in SPSS software, using one-way ANOVA. Hill-Bone medication adherence scale was completed by all the participants before and three months after the intervention. Data analysis was performed in SPSS software, using one-way ANOVA. RESULTS: The results of ANOVA test demonstrated that the mean scores of medication adherence were statistically different among the three groups of control (46.63+/-2.99), SMS (57.70+/-2.75) and the reminder cards (57.51+/-2.69) after the intervention (P<0.001). However, after the intervention the means of the patients' medication adherence scores were not statistically different between the two groups trained via SMS and reminder cards (P>0.05). CONCLUSION: The findings of the present research demonstrated that training and distance monitoring via SMS and reminder cards promote medication adherence of patients. Therefore, healthcare teams and nurses are recommended to apply such training methods. TRIAL REGISTRATION NUMBER: IRCT2015110917059N2. PMID- 27382588 TI - Vulnerable Women's Self-Care Needs in Knowledge, Attitude and Practice Concerning Sexually Transmitted Diseases. AB - BACKGROUND: Vulnerable women are prone to sexually transmitted diseases (STD) due to their special conditions and poor knowledge about these diseases in the society. Therefore, the present study aimed to determine the vulnerable women's self-care needs in knowledge, attitude and practice concerning STD. METHODS: This is a cross-sectional-descriptive study conducted in 2014. The data collection was carried out using a self-administered structured questionnaire. 120 vulnerable women referring to centers affiliated to health and well-being center in Isfahan participated in this study. They were selected through proportional rationing sampling and filled out a researcher developed questionnaire containing information on personal characteristics, self-care knowledge, attitude, and practice needs toward the STD. The data were analyzed using statistical methods including Spearman & Pearson correlation co-efficient, independent t-test and ANOVA. All analyses were carried out using SPSS, 20. RESULTS: Based on the results, most of the subjects mentioned that their priorities of self-care needs in domains of knowledge, attitude and practice were "familiarization with the types and contamination ways of sexually transmitted diseases" (57.9%); "diagnosis of STD only makes us anxious" (24.8), and "the method of washing the genital area before and after intercourse" 41.3%), respectively. There was a significant association among marital status, education, history of addiction, and self-care needs in domains of knowledge, attitude and practice (P<0.05). CONCLUSION: Results showed that vulnerable women not only knew their need about STD, but also paid attention to their attitude and practice needs toward STD. Therefore, educational programs should be designed and administrated by the experts, based on vulnerable women's self-care needs concerning their knowledge, attitude and practice to prevent and control STD in vulnerable individuals. PMID- 27382589 TI - The Effect of Family-Centered Psycho-Education on Mental Health and Quality of Life of Families of Adolescents with Bipolar Mood Disorder: A Randomized Controlled Clinical Trial. AB - BACKGROUND: Bipolar Mood Disorder (BMD) is a type of mood disorder which is associated with various disabilities. The family members of the patients with BMD experience many difficulties and pressures during the periods of treatment, rehabilitation and recovery and their quality of life (QOL) is threatened. In the present study, we aimed to evaluate the effect of family-centered education on mental health and QOL of families with adolescents suffering from BMD. METHODS: In this randomized controlled clinical trial performed on 40 families which were mostly mothers of the adolescents with BMD referred to the psychiatric clinics affiliated to Shiraz University of Medical Sciences during 2012-13. They were randomly assigned to intervention and control groups. RESULTS: The results of single factor multivariate ANOVA/single-factor multivariate analysis of variance and Bonferroni post hoc tests showed that the interaction between the variables of group and time was significant (P<0.001). The mean of QOL and mental health scores increased in the intervention group, but it decreased in the control group at three measurement time points. CONCLUSION: The study findings confirmed the effectiveness of family-centered psychoeducation program on Mental Health and Quality of life of the families of adolescents with Bipolar Mood Disorder. TRIAL REGISTRATION NUMBER: IRCT201304202812N15. PMID- 27382590 TI - The Effect of Follow up (Telenursing) on Liver Enzymes in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial. AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is characterized by macro vesicular steatosis in the absence of alcohol. Patients with (NAFLD)need extensive education and support in their treatment. Our aim was to investigate the effect of telenursing on liver enzymes (ALT and AST) in patients with NAFLD. METHODS: Our study is a randomized controlled clinical trial. In this study, 60 patients were enrolled from patients who referred to subspecialty gastrointestinal clinics affiliated to Shiraz University of Medical Sciences. Specialists confirmed their diseases by ultrasound and laboratory test. Simple randomization, based on random number table, was used to randomize the participants into intervention (N=30) and control (N=30) groups. Patients in both groups received dietary advice from a nutritionist and were trained to perform physical activities. Telephone intervention in the intervention group lasted for 12 weeks, in order to see the effect of follow up on the recommended diet and physical activities given by the specialist, while; the control group subjects were only followed up as usual by their physician. RESULTS: The result of an independent t-test showed that the mean difference of liver Enzymes between the two groups was statistically significant (P<0.001). The difference of AST and ALT in the intervention and control groups was 18.03, -1.27 and 40.70, 1.52, respectively. CONCLUSION: We found out that; telenursing could have a positive effect on reduction of liver enzymes (ALT, AST) in patients with NAFLD. TRIAL REGISTRATION NUMBER: IRCT2015040411691N5. PMID- 27382591 TI - Effect of Orem's Self-Care Model on Perceived Stress in Adolescents with Asthma Referring the Asthma and Allergy Clinic, Isfahan, 2014. AB - BACKGROUND: Incidence of asthma in adolescents leads to variations in family status, roles and interaction with peers for them, which could be a source of stress and psychological tensions in them. Therefore, the present study was conducted to investigate the effect of Orem's self-care model on perceived stress in adolescents with asthma. METHODS: In this semi-experimental study conducted from April 2013 to February 2014, 64 asthmatic adolescents referring Shariati Hospital, Isfahan were enrolled by simple random sampling and the patients were assigned to two groups of control and intervention. Then, Orem's self-care model based training was implemented throughout eight sessions of two hours each and the Cohen Perceived Stress Scale was administered to both groups prior to and two months after the completion of the training. The data were analyzed by descriptive and analytical statistics consisting of paired t-test, independent t test, Chi-square and Mann-Whitney using SPSS Version 20. RESULTS: Mean age of the participants was 14.15+/-3.12 years in the intervention group and 15.21+/-3.09 years in the control groups. 68.8% and 59.4% of the participants were male in the intervention and control groups, respectively. Independent t-test indicated a significant difference in the mean scores of perceived stress in the intervention (25.46+/-5.31) and control groups (28.90+/-5.27) after the training. Also, the result of paired t-test indicated a significant difference in the mean score of perceived stress between before (29.18+/-5.27) and after (25.46+/-5.31) training. CONCLUSION: As the training based on Orem's model had a positive effect on declining perceived stress in asthmatic adolescents, continuation of using these training interventions could contribute to ultimately achieving positive outcomes in health functions of these patients. PMID- 27382592 TI - Effect of Self Care Education with and without Telephone Follow-Up on the Level of Hope in Renal Dialysis Patients: A Single-Blind Randomized Controlled Clinical Trial. AB - BACKGROUND: Various strategies such as teaching self care to hemodialysis patients have been employed to increase the level of their hope. This study aimed at examining the effects of a telephone follow-up program on the level of hope in a self care education program. METHODS: In this single-blind randomized controlled clinical trial, 75 hemodialysis patients, selected by convenient sampling, were randomly assigned to 3 groups (n=25 each) including a control, a self care education, or a self care education with telephone follow-up. The control group received the routine care. The self care education group received 5 instruction sessions. The telephone follow-up group had similar instructional sessions followed by telephone calls during the subsequent 2 months. Data, collected using demographic information list and Miller's hope questionnaire, were analyzed using Chi-Square, t-test, and one-way ANOVA followed by Scheffee test. RESULTS: There was no significant difference among the scores of hope in the three groups before the intervention (P=0.40). However, after the intervention, the level of hope in the self care education group and self care education plus telephone follow-up groups were significantly higher than that of the control group (P=0.001). Moreover, the level of hope in the group with self care education plus telephone follow-up was significantly (P=0.001) more than that of the self care education group. CONCLUSION: Our findings indicated that teaching followed by telephone follow-up was associated with higher levels of hope. Therefore, such a strategy may be employed to improve the quality of life of patients with renal dialysis. TRIAL REGISTRATION NUMBER: IRCT2014042617440N1. PMID- 27382593 TI - Managing Parenting Stress through Life Skills Training: A Supportive Intervention for Mothers with Visually Impaired Children. AB - BACKGROUND: Vision impairment in children is one of the most severe disabilities that cause stress in parents. Therefore, it seems necessary to establish and conduct interventions for controlling parenting stress and preventing its negative consequences. This study aimed to investigate the effect of life skills training (LST) program on parenting stress of mothers with blind children aged 7 to 12 years. METHODS: This study was a non-blinded randomized controlled trial. 52 mothers with blind children studying at Shoorideh Shirazi educational complex, Shiraz, Iran in 2013 were enrolled, using census sampling method. Balanced block randomization method was used to allocate the participants to groups. The intervention group participated in an LST program consisting of 5 two-hour sessions per week for 5 consecutive weeks but the control group didn't. Data were collected using a demographic questionnaire and Parenting Stress Index; they were completed three times by the participants of both groups before, immediately after, and one month after the intervention. Collected data were analyzed using Chi-square, independent t-test and repeated measures analysis of variances (ANOVA). RESULTS: The LST program could decrease parenting stress in the intervention group mothers (P<0/001). This statistically significant reduction in the mean scores of parenting stress was observed in both children and parents. CONCLUSION: LST program could reduce parenting stress in mothers with blind children. Therefore, it can be used as an efficient, cost-effective and simple technique for managing parenting stress in such parents. TRIAL REGISTRATION NUMBER: IRCT201405147531N6. PMID- 27382594 TI - A Comparative Study of Potassium Hydroxide versus CO2 Laser Vaporization in The Treatment of Female Genital Warts: A Controlled Clinical Trial. AB - BACKGROUND: Genital warts are the most common viral sexually transmitted disease affecting 1% of the population. A prospective, open-label controlled trial was performed to compare topical 5% potassium hydroxide (KOH) solution with CO2 laser in the treatment of female genital warts. METHODS: Seventy patients were enrolled in the study after convenience sampling. Right-sided lesions of the patients were treated by CO2 laser every 3 weeks. The left-sided lesions of the same patients were treated by topical 5% KOH solution twice a day using a toothpick with cotton wrap on the tip. The patients were visited at 3, 6, and 9 weeks after initiation of the treatment and followed up for 6 months after the last visit. RESULTS: Out of seventy patients, sixty three completed the study and were analyzed. A total of 56 KOH treated-patients (88.9%) showed complete response. On the other hand, 56 laser-treated patients (88.9%) presented complete clearing of the lesion. There was not any difference in response to both modalities of treatment. Complications of KOH solution and CO2 laser were 24% and 19% respectively (P>0.05), but serious adverse events were not observed. The patients under KOH treatment displayed a recurrence rate of 11.1% (7 cases), while the same patients with CO2 laser therapy demonstrated a recurrence rate of 7.9% (5 cases) (P=0.54). CONCLUSION: Topical 5% KOH solution was as effective as CO2 laser in the treatment of female genital warts. There was not any serious complication in the application of KOH solution. This could be used as a new treatment for genital warts. TRIAL REGISTRATION NUMBER: IRCT201412207848N1. PMID- 27382595 TI - Effect of Charity Rehabilitation Centers on the Welfare of Mentally Disabled Children. PMID- 27382596 TI - Consideration of corneal biomechanics in the diagnosis and management of keratoconus: is it important? AB - Keratoconus is a bilateral, non-inflammatory, degenerative corneal disease. The occurrence and development of keratoconus is associated with corneal thinning and conical protrusion, which causes irregular astigmatism. With the disruption of the collagen organization, the cornea loses its shape and function resulting in progressive visual degradation. Currently, corneal topography is the most important tool for the diagnosis of keratoconus, which may lead to false negatives among the patient population in the subclinical phase. However, it is now hypothesised that biomechanical destabilisation of the cornea may take place ahead of the topographic evidence of keratoconus, hence possibly assisting with disease diagnosis and management. This article provides a review of the definition, diagnosis, and management strategies for keratoconus based on corneal biomechanics. PMID- 27382597 TI - Noninferior Antibiotics: When Is "Not Bad" "Good Enough"? AB - Novel treatment options are urgently needed for patients with serious multidrug resistant infections seen increasingly in routine everyday clinical practice, both in the hospital and nursing home as well as in the clinic and office setting. Unfortunately, the problem is no longer confined to chronically ill, repeatedly hospitalized patients. This essay explores the role of noninferiorly studies in addressing the pressing need for new antimicrobial agents to combat the emerging "superbugs", calling attention to the nuances of interpreting their sometimes less-than-straightforward results. The overriding aim is not to find better antibiotics for routinely treatable infections but to identify safe and efficacious treatment options where none presently exist. PMID- 27382598 TI - A Survey and Analysis of the American Public's Perceptions and Knowledge About Antibiotic Resistance. AB - Background. Little is known about the American public's perceptions or knowledge about antibiotic-resistant bacteria or antibiotic misuse. We hypothesized that although many people recognize antibiotic resistance as a problem, they may not understand the relationship between antibiotic consumption and selection of resistant bacteria. Methods. We developed and tested a survey asking respondents about their perceptions and knowledge regarding appropriate antibiotic use. Respondents were recruited with the Amazon Mechanical Turk crowdsourcing platform. The survey, carefully designed to assess a crowd-sourced population, asked respondents to explain "antibiotic resistance" in their own words. Subsequent questions were multiple choice. Results. Of 215 respondents, the vast majority agreed that inappropriate antibiotic use contributes to antibiotic resistance (92%), whereas a notable proportion (70%) responded neutrally or disagreed with the statement that antibiotic resistance is a problem. Over 40% of respondents indicated that antibiotics were the best choice to treat a fever or a runny nose and sore throat. Major themes from the free-text responses included that antibiotic resistance develops by bacteria, or by the infection, or the body (ie, an immune response). Minor themes included antibiotic overuse and antibiotic resistance caused by bacterial adaptation or an immune response. Conclusions. Our findings indicate that the public is aware that antibiotic misuse contributes to antibiotic resistance, but many do not consider it to be an important problem. The free-text responses suggest specific educational targets, including the difference between an immune response and bacterial adaptation, to increase awareness and understanding of antibiotic resistance. PMID- 27382599 TI - When Antimicrobial Stewardship Isn't Watching: The Educational Impact of Critical Care Prospective Audit and Feedback. AB - Prospective audit and feedback (PAF) is an effective strategy to optimize antimicrobial use in the critical care setting, yet whether skills gained during PAF influence future antimicrobial prescribing is uncertain. This multisite study demonstrates that knowledge learned during PAF is translated and incorporated into the practice of critical care physicians even when not supported by an antimicrobial stewardship program. PMID- 27382600 TI - Risk Factors for Herpes Zoster Among Adults. AB - Background. The causes of varicella-zoster virus reactivation and herpes zoster (HZ) are largely unknown. We assessed potential risk factors for HZ, the data for which cannot be obtained from the medical sector. Methods. We conducted a matched case-control study. We established active surveillance in Olmsted County, Minnesota to identify HZ occurring among persons age >=50 years during 2010-2011. Cases were confirmed by medical record review. Herpes zoster-free controls were age- and sex-matched to cases. Risk factor data were obtained by telephone interview. Results. We enrolled 389 HZ case patients and 511 matched controls; the median age was 65 and 66 years, respectively. Herpes zoster was associated with family history of HZ (adjusted odds ratio [aOR] = 1.65); association was highest with first-degree or multiple relatives (aOR = 1.87 and 3.08, respectively). Herpes zoster was also associated with prior HZ episodes (aOR = 1.82), sleep disturbance (aOR = 2.52), depression (aOR = 3.81), and recent weight loss (aOR = 1.95). Stress was a risk factor for HZ (aOR = 2.80), whereas a dose response relationship was not noted. All associations indicated were statistically significant (P < .05). Herpes zoster was not associated with trauma, smoking, tonsillectomy, diet, or reported exposure to pesticides or herbicides (P > .1). Conclusions. We identified several important risk factors for HZ; however, the key attributable causes of HZ remain unknown. PMID- 27382601 TI - An HSV-based library screen identifies PP1alpha as a negative TRPV1 regulator with analgesic activity in models of pain. AB - Transient receptor potential vanilloid 1 (TRPV1) is a pronociceptive cation channel involved in persistent inflammatory and neuropathic pain. Herpes simplex virus (HSV) vector expression of TRPV1 causes cell death in the presence of capsaicin, thereby completely blocking virus replication. Here we describe a selection system for negative regulators of TRPV1 based on rescue of virus replication. HSV-based coexpression of TRPV1 and a PC12 cell-derived cDNA library identified protein phosphatase 1alpha (PP1alpha) as a negative regulator of TRPV1, mimicking the activity of "poreless" (PL), a dominant-negative mutant of TRPV1. Vectors expressing PP1alpha or PL reduced thermal sensitivity following virus injection into rat footpads, but failed to reduce the nocifensive responses to menthol/icilin-activated cold pain or formalin, demonstrating that the activity identified in vitro is functional in vivo with a degree of specificity. This system should prove powerful for identifying other cellular factors that can inhibit ion channel activity. PMID- 27382602 TI - Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs. AB - Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein 90alpha is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5-treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing. PMID- 27382603 TI - Moving toward a higher efficiency of microcell-mediated chromosome transfer. AB - Microcell-mediated chromosome transfer (MMCT) technology enables individual mammalian chromosomes, megabase-sized chromosome fragments, or mammalian artificial chromosomes that include human artificial chromosomes (HACs) and mouse artificial chromosomes (MACs) to be transferred from donor to recipient cells. In the past few decades, MMCT has been applied to various studies, including mapping the genes, analysis of chromosome status such as aneuploidy and epigenetics. Recently, MMCT was applied to transfer MACs/HACs carrying entire chromosomal copies of genes for genes function studies and has potential for regenerative medicine. However, a safe and efficient MMCT technique remains an important challenge. The original MMCT protocol includes treatment of donor cells by Colcemid to induce micronucleation, where each chromosome becomes surrounded with a nuclear membrane, followed by disarrangement of the actin cytoskeleton using Cytochalasin B to help induce microcells formation. In this study, we modified the protocol and demonstrated that replacing Colcemid and Cytochalasin B with TN 16 + Griseofulvin and Latrunculin B in combination with a Collage/Laminin surface coating increases the efficiency of HAC transfer to recipient cells by almost sixfold and is possibly less damaging to HAC than the standard MMCT method. We tested the improved MMCT protocol on four recipient cell lines, including human mesenchymal stem cells and mouse embryonic stem cells that could facilitate the cell engineering by HACs. PMID- 27382605 TI - L-Asparaginase Activity of Fungal Endophytes from Tabernaemontana heyneana Wall. (Apocynaceae), Endemic to the Western Ghats (India). AB - "Endophytes," the microbes residing within the plant tissues, are important sources of secondary metabolites. Tabernaemontana heyneana Wall., a medicinal tree, endemic to the Western Ghats with rich ethnobotanical history and unique chemical diversity, was selected to study fungal endophytes and evaluate them for L-asparaginase activity. Healthy plant parts were selected for the isolation of endophytes following standard isolation protocols. A total of 727 isolates belonging to 20 taxa were obtained. The isolates comprised of bark (11%), twig (22%), leaf (43%), fruit (12.0%), and seeds (12%). Endophytes such as Colletotrichum, Curvularia, Fusarium, Phomopsis, Verticillium, and Volutella colonized T. heyneana plant parts. Fusarium sp., Phomopsis spp., isolate Thlf01, and Fusarium solani were the dominant genera of bark, twig, leaf, fruits, and seed samples, respectively. The endophytes were screened for their ability to utilize L-asparagine by plate assay method. Fusarium spp. exhibited a high level of activity among the nine endophytes tested positive for L-asparaginase activity. Studies underline the potentials of endophyte-derived fungal L asparaginases as sources of chemotherapeutic agents. PMID- 27382604 TI - Study of Natural Cytotoxicity Receptors in Patients with HIV/AIDS and Cancer: A Cross-Sectional Study. AB - The NCR receptors play a fundamental role in the cytotoxicity mediated by NK cells against tumor cells. In the current study, we investigated possible HIV/AIDS-related changes in the expression of the NCR receptors comparing healthy donors, HIV/AIDS patients, and HIV/AIDS patients with cancer (HIV/AIDSWC). The NCRs were quantified in NK cells (NK(dim) and NK(bright)) and T lymphocytes from peripheral blood samples by flow cytometry. We found a significant decrease in the frequency of NK cells expressing NKp46 in HIV/AIDS group (p = 0.0012). There was a decrease in the frequency of NK cells expressing NKp46 in the HIV/AIDSWC group; however, this was not statistically significant. We found a significant decrease in the frequency of NK cells expressing NKp30 in the HIV/AIDS group (p = 0.0144). There was a decrease in the frequency of NK cells expressing NKp30 and in the HIV/AIDSWC group, but this was not statistically significant. There were no changes in the distribution of NK cells and their subtypes in both groups. PMID- 27382606 TI - Vertebral Artery Hypoplasia in a Black Kenyan Population. AB - This study examined the characteristics of vertebral artery hypoplasia in 346 arteries of adult black Kenyans. The circumference was measured on haematoxylin/eosin stained microscopic sections of the distal one-third of the intracranial vertebral arteries using scion image analyser. Internal diameter was calculated in millimetre. Data were analysed using SPSS version 16.0. Vertebral artery hypoplasia (diameter < 2.0 mm) occurred in 100 (28.9%) arteries. Sixty of these (17.3%) were on the left and 40 (11.6%) on the right. Sixty (17.3%) were in females while 40 (11.6%) were in males. The side and gender differences were statistically significant at confidence interval of 95%. Frequency of vertebral artery hypoplasia was higher than in most other populations studied. The condition differs from that in other populations because it is more common on the left side and in females. We recommend ultrasound, angio-CT, or angio-MRI evaluation of vertebral arterial system before diagnostic or interventional procedures on posterior circulation. PMID- 27382607 TI - Hydroxyapatite-Based Colloidal Gels Facilitate the Proliferation and Migration of Chondrocytes and the Adhesion of Umbilical Cord Mesenchymal Stem Cells. AB - Collective movement of cells that have been delivered on biomaterials for transplantation purposes would be a desirable attribute that would promote wound healing, cell proliferation, and eventual growth and regeneration of damaged organs. We hypothesized that colloidal gels made from hydroxyapatite (HA) and poly(D,L-lactic-co-glycolic acid) (PLGA) particles will be conducive to the growth and migration of porcine chondrocytes, will allow the adhesion of human umbilical cord mesenchymal stem cells, and will have negligible effects on the cell cycle of these cells. Then, we performed experiments designed to assess the viability and migratory properties of porcine chondrocytes studded on nanosized HA/PLGA particles. Our experiments show that porcine chondrocytes migrated in and around a hydroxyapatite-based biomaterial that could be described as a colloidal gel. Cells in the colloidal gel demonstrated unidirectional movement. Cells were seen to be extending lamellae and were followed by other cells. PMID- 27382608 TI - Entrapment of alpha-Amylase in Agar Beads for Biocatalysis of Macromolecular Substrate. AB - Attempts have been made to optimize immobilization parameters, catalytic property, and stability of immobilized alpha-amylase in agar. The work compares natural entrapment efficiency of agar with the ionotropically cross-linked agar hydrogel, with the advantage of easy scale-up and cost and time effectiveness. Beads prepared with 3% (w/v) agar and 75 mM calcium chloride and hardened for 20 minutes were selected for further studies on the basis of entrapment efficiency (80%) and physical stability. Following entrapment, pH and temperature optima of enzyme were shifted from 6 to 6.5 and 50 to 55 degrees C, respectively. Michaelis constant (K m ) for both free and entrapped enzymes remained the same (0.83%) suggesting no change in substrate affinity. However, V max? of entrapped enzyme decreased ~37.5-fold. The midpoint of thermal inactivation for entrapped enzyme increased by 8 +/- 1 degrees C implying its higher thermal stability. The entrapped enzyme in calcium agar bead had an Ea value of 27.49 kcal/mol compared to 17.6 kcal/mol for free enzyme indicating increased stability on entrapment. Half-life of enzyme increased ~2.2 times after entrapment in calcium agar at 60 degrees C indicating stabilization of enzyme. The reusability of beads was size dependent. Beads with diameter <710 MUm were stable and could be reused for 6 cycles with ~22% loss in activity. PMID- 27382609 TI - Comparison of Two Doses of Ropivacaine Hydrochloride for Lumbosacral Epidural Anaesthesia in Goats Undergoing Laparoscopy Assisted Embryo Transfer. AB - Goats (n = 12) undergoing laparoscopy assisted embryo transfer were randomly allotted to two groups (I and II) and injected same volume of ropivacaine hydrochloride at 1.0 mg/kg and 0.5 mg/kg body weight, respectively, at the lumbosacral epidural space. The hind quarters of all the animals were lifted up for the first 3.0 minutes following injection. Immediately after induction the animals were restrained in dorsal recumbency in Trendelenburg position in a cradle. Laparoscopy was performed after achieving pneumoperitoneum using filtered room air. Regional analgesia and changes in physiological parameters were recorded. The mean induction time in animals of group I (n = 6) was 12.666 +/- 1.994 minutes. In these animals the analgesia extended up to the umbilical region and lasted for 60 minutes. Only two animals in group II were satisfactorily induced in 11.333 +/- 2.333 minutes. In animals of group I, the time taken for regaining the full motor power was significantly long (405 +/- 46.314 min) when compared to group II goats (95 +/- 9.219 min). From this study it was concluded that ropivacaine did not produce adequate analgesia in most of the goats at 0.5 mg/kg. When used at 1.0 mg/kg, it produced satisfactory regional analgesia lasting for one hour but the prolonged motor loss precludes its use. Additional studies using ropivacaine hydrochloride at doses in between the two extremes used here may be undertaken before recommending it for lumbosacral anaesthesia in goats undergoing laparoscopy. PMID- 27382610 TI - Joint Estimation of Time-Frequency Signature and DOA Based on STFD for Multicomponent Chirp Signals. AB - In the study of the joint estimation of time-frequency signature and direction of arrival (DOA) for multicomponent chirp signals, an estimation method based on spatial time-frequency distributions (STFDs) is proposed in this paper. Firstly, array signal model for multicomponent chirp signals is presented and then array processing is applied in time-frequency analysis to mitigate cross-terms. According to the results of the array processing, Hough transform is performed and the estimation of time-frequency signature is obtained. Subsequently, subspace method for DOA estimation based on STFD matrix is achieved. Simulation results demonstrate the validity of the proposed method. PMID- 27382612 TI - Scenario Studies on Effects of Soil Infiltration Rates, Land Slope, and Furrow Irrigation Characteristics on Furrow Irrigation-Induced Erosion. AB - Furrow irrigation proceeds under several soil-water-furrow hydraulics interaction dynamics. The soil erosion consequences from such interactions in furrow irrigation in Samaru had remained uncertain. A furrow irrigation-induced erosion (FIIE) model was used to simulate the potential severity of soil erosion in irrigated furrows due to interactive effects of infiltration rates, land slope, and some furrow irrigation characteristics under different scenarios. The furrow irrigation characteristics considered were furrow lengths, widths, and stream sizes. The model itself was developed using the dimensional analysis approach. The scenarios studied were the interactive effects of furrow lengths, furrow widths, and slopes steepness; infiltration rates and furrow lengths; and stream sizes, furrow lengths, and slopes steepness on potential furrow irrigation induced erosion, respectively. The severity of FIIE was found to relate somewhat linearly with slope and stream size, and inversely with furrow lengths and furrow width. The worst soil erosion (378.05 t/ha/yr) was found as a result of the interactive effects of 0.65 m furrow width, 50 m furrow length, and 0.25% slope steepness; and the least soil erosion (0.013 t/ha/yr) was induced by the combined effects of 0.5 l/s, 200 m furrow length, and 0.05% slope steepness. Evidently considering longer furrows in furrow irrigation designs would be a better alternative of averting excessive FIIE. PMID- 27382611 TI - Pharmacological and Ethnomedicinal Overview of Heritiera fomes: Future Prospects. AB - Mangrove plants are specialized woody plants growing in the swamps of tidal coastal areas and river deltas of tropical and subtropical parts of the world. They have been utilized for medicinal and other purposes by the coastal people over the years. Heritiera fomes Buch. Ham. (family: Sterculiaceae) commonly known as Sundari (Bengali) is a preeminent mangrove plant occurring in the Sundarbans forest located in the southern part of Bangladesh and adjoining West Bengal province of India. The plant has applications in traditional folk medicine as evidenced by its extensive use for treating diabetes, hepatic disorders, gastrointestinal disorders, goiter, and skin diseases by the local people and traditional health practitioners. A number of investigations indicated that the plant possesses significant antioxidant, antinociceptive, antihyperglycemic, antimicrobial, and anticancer activities. Phytochemical analyses have revealed the presence of important chemical constituents like saponins, alkaloids, glycosides, tannins, steroids, flavonoids, gums, phytosterols, and reducing sugars. The present study is aimed at compiling information on phytochemical, biological, pharmacological, and ethnobotanical properties of this important medicinal plant, with a view to critically assess the legitimacy of the use of this plant in the aforementioned disorders as well as providing directions for further research. PMID- 27382613 TI - Vitamin D and Its Role as a Protective Factor in Allergy. AB - The relationship between vitamin D status and asthma has been subject to several studies in the last decade. Epidemiological data suggest that incidence of asthma and atopic diseases increased significantly in most Westernized countries. The significant variation between countries suggests that besides genetic factors, environmental aspects play a role in the pathogenesis of atopy. The prevalence of hypovitaminosis D is high in many industrialized countries. In addition to its relationship with bone metabolism, vitamin D is recognized as an immunomodulator, with important effects on both adaptive and innate immunity. Correlations between vitamin D status and asthma have been formulated, with a considerable interest in assessing whether this vitamin protects against or reduces asthma morbidity. In this review, we discuss recent findings regarding vitamin D status throughout Europe and its influence over asthma and allergic rhinitis prevalence. Geographical latitude and dietary habits may explain the lower prevalence of allergic disease in Albania. We also consider the effects of vitamin D supplementation in allergic disease. Several clinical trials are under way and their results are needed in order to make definitive recommendations about the optimal dose of vitamin D for prevention and treatment of asthma and allergic disease. PMID- 27382615 TI - Clinical Outcomes of Radial Shortening Osteotomy and Vascularized Bone Graft in Kienbock's Disease. AB - The aim of this study was to compare two surgery methods including radial shortening and radial shortening combined with vascularized bone graft for treatment of stage II or IIIa of Kienbock's disease. It is a randomized, controlled clinical trial, which was carried out in 2011-2013. Twenty-four patients were assigned equally to radial shortening group (A) or radial shortening combined with vascularized bone graft group (B). The outcome was assessed by Mayo Wrist score before and 9 months after surgery. The mean Mayo Wrist score (SD) was 27.1 (15.4) and 32.5 (18.3) before surgery and 74.6 (5.4) and 85.8 (5.1) after surgery for groups A and B, respectively. The mean score increased in both groups, and it was higher in group B significantly. Radial shortening combined with vascularized bone graft is a valuable method which can be more effective than radial shortening alone, in early stages of Kienbock's disease. This trial is registered with IRCT201404127841N5. PMID- 27382616 TI - Prediction of Slot Shape and Slot Size for Improving the Performance of Microstrip Antennas Using Knowledge-Based Neural Networks. AB - In the last decade, artificial neural networks have become very popular techniques for computing different performance parameters of microstrip antennas. The proposed work illustrates a knowledge-based neural networks model for predicting the appropriate shape and accurate size of the slot introduced on the radiating patch for achieving desired level of resonance, gain, directivity, antenna efficiency, and radiation efficiency for dual-frequency operation. By incorporating prior knowledge in neural model, the number of required training patterns is drastically reduced. Further, the neural model incorporated with prior knowledge can be used for predicting response in extrapolation region beyond the training patterns region. For validation, a prototype is also fabricated and its performance parameters are measured. A very good agreement is attained between measured, simulated, and predicted results. PMID- 27382614 TI - Recent Advancements in Prognostic Factors of Epithelial Ovarian Carcinoma. AB - Ovarian cancer remains the most common cause of gynecologic cancer-related death among women in developed countries. Nevertheless, subgroups of ovarian cancer patients experience relatively longer survival. Efforts to identify prognostic factors that characterize such patients are ongoing, with investigational areas including tumor characteristics, surgical management, inheritance patterns, immunologic factors, and genomic patterns. This review discusses various demographic, clinical, and molecular factors implicating longevity and ovarian cancer survival. Continued efforts at identifying these prognosticators may result in invaluable adjuncts to the treatment of ovarian cancer, with the ultimate goal of advancing patient care. PMID- 27382617 TI - Impact of New Water Sources on the Overall Water Network: An Optimisation Approach. AB - A mathematical programming problem is formulated for a water network with new water sources included. Salinity and water hardness are considered in the model, which is later solved using the Max-Min Ant System (MMAS) to assess the impact of new water sources on the total cost of the existing network. It is efficient to include new water sources if the distances to them are short or if there is a high penalty associated with failure to meet demand. Desalination unit costs also significantly affect the decision whether to install new water sources into the existing network while softening costs are generally negligible in making such decisions. Experimental results show that, in the example considered, it is efficient to reduce number of desalination plants to remain with one central plant. The Max-Min Ant System algorithm seems to be an effective method as shown by least computational time as compared to the commercial solver Cplex. PMID- 27382618 TI - Comparison of Fusion Rates between Glycerol-Preserved and Frozen Composite Allografts in Cervical Fusion. AB - Background. This retrospective, two cohort series study was designed to compare a room temperature, glycerol-preserved composite pinned bone allograft (G-CPBA) with the same graft type provided in a frozen state (F-CPBA) for use as a cervical interbody spacer in anterior cervical discectomy and fusion (ACDF). Methods. A comprehensive chart review was performed for 67 sequential patients that received either a F-CPBA or a G-CPBA and had at least one-year follow-up. Twenty-eight patients had received G-CPBA grafts and 37 patients had received F CPBA grafts. Two additional 2-level patients had received one of each type of grafts. Results. At 3 months, 45.3% (29 of 64) of glycerol-preserved and 41.4% (29 of 70) of frozen allografts, respectively, were considered to be fused radiographically. At 12 months, 100% of both treatment groups (41 glycerol preserved and 45 frozen) were considered fused. Fusion rates for G-CPBA were statistically similar to F-CPBA at both 3 and 12 months (P = 0.6535 and >0.999, resp.). There were no allograft related complications in either treatment group. Conclusions. 100% fusion rates were attained by both treatment groups at 12 months and were similar at short-term follow-up for all comparable levels. Level of Evidence. Level of evidence is III. PMID- 27382619 TI - Self-Microemulsifying Drug Delivery Systems: An Attractive Strategy for Enhanced Therapeutic Profile. AB - Ease of administration and painless approach made oral route the most preferred. Poor oral bioavailability is pronounced with the majority of recent active ingredients because of dissolution rate limited absorption. Failure to attain intended therapeutic effect of the poor water soluble drugs by this route led to development of novel drug delivery systems which will fulfill therapeutic needs with minimum dose. Although many formulation approaches like solid dispersions, complexation, pH modification, and cocrystals exist, lipid based delivery systems finding increased appliance with the apparent increase in absorption of drug. Among lipid based formulations, self-microemulsifying formulations (droplet size < 100 nm) are evident to improve the oral bioavailability of hydrophobic drugs primarily due to their efficiency in facilitating solubilization and in presenting the hydrophobic drug in solubilized form whereby dissolution process can be circumvented. Various components that are used to formulate these dosage forms like surfactants and lipids contribute to the overall improvement in oral bioavailability via promoting the lymphatic transport; thereby hepatic first pass metabolism can be surmounted. The present paper gives exhaustive information on the formulation design and characterization of SMEDDS along with the probable mechanisms by which the bioavailability can be improved with SMEDDS. PMID- 27382621 TI - Comparative Study on the Efficacy of Anorganic Bovine Bone (Bio-Oss) and Nanocrystalline Hydroxyapatite (Ostim) in Maxillary Sinus Floor Augmentation. AB - Purpose. The aim of this study was to evaluate the efficacy of anorganic bovine bone (Bio-Oss) in comparison with nanocrystalline hydroxyapatite (Ostim) in sinus floor augmentation. Methods. Ten patients aged 40-80 were selected. All the patients needed sinus floor augmentation due to insufficient bone for simultaneous implant placement. The patients underwent panoramic radiography and cone beam computed tomography (CBCT) prior to surgical procedure. After lifting the sinus membrane, Bio-Oss and Ostim are randomly grafted at one of the two sides. Biopsies were obtained from areas identified 5 months after the surgery and before implant placement and then were prepared for histological analysis. Statistical analysis was performed with nonparametric Wilcoxon signed-rank test for comparison of histological and radiological parameters between the two groups. Results. Histological findings revealed a significant increase in percentages of new bone in the Ostim group (P = 0.015). Furthermore, new bone density was greater with Ostim compared to Bio-Oss (P = 0.038); however, the difference in height increase after surgery did not reach statistical significance (P = 0.191). Conclusion. Despite the limitations of this trial, Ostim and Bio-Oss are useful biomaterials in sinus augmentation and Ostim seems to be even more effective in new bone formation. PMID- 27382620 TI - Corticosteroid Treatment Impact on Spinal Deformity in Duchenne Muscular Dystrophy. AB - Duchenne muscular dystrophy is a progressive disease with loss of ambulation at around 9-10 years of age, followed, if untreated, by development of scoliosis, respiratory insufficiency, and death in the second decade of life. This review highlights the natural history of the disease, in particular, with regard to the development of the spinal deformity and how this complication has been modified by surgical interventions and overall by corticosteroid treatment. The beneficial effect of corticosteroids may have also an impact on the clinical trial design of the new emerging causative therapies. PMID- 27382623 TI - Epidemiology of Bovine Mastitis in Cows of Dharwad District. AB - Bovine mastitis is very common in cows of both developed and developing countries. The prevalence of clinical and subclinical mastitis (SCM) varies from region to region. Hence, the present study was carried out to determine the prevalence of mastitis using three diagnostic tests by considering different risk factors like age, lactation, breed, season, quarters, and herd. The results showed that surf field mastitis test (SFMT) is the most sensitive test for diagnosis of bovine mastitis, the older age and cows with later part of lactation period were more prone to bovine mastitis, and exotic breeds like Holstein freshen (HF) were more susceptible to bovine mastitis. The highest incidence of mastitis was recorded in monsoon season. The prevalence of subclinical and clinical mastitis was more in single and two quarters, respectively, and the rate of bovine mastitis was more in unorganized herds. The study concluded that SCM is directly associated with age, lactation period, and environmental factors of the cow and clinical mastitis is more associated with breed of the cow and environmental conditions. PMID- 27382624 TI - Recovery of Ga(III) by Raw and Alkali Treated Citrus limetta Peels. AB - Alkali treated Citrus limetta peels were used for recovery of Ga(III) from its aqueous solution. The raw and alkali treated peels were characterized for functional groups. The efficiency of adsorption increased from 47.62 mg/g for raw peels to 83.33 mg/g for alkali treated peels. Between pH 1 and 3, the adsorption increased and thereafter decreased drastically. The adsorption followed pseudosecond order kinetics and Langmuir isotherm gave the best fit for the experimental data. Desorption studies showed 95.28% desorption after 3 cycles for raw peels while it was 89.51% for alkali treated peels. Simulated Bayer liquor showed 39.57% adsorption for gallium ions on raw peels which was enhanced to 41.13% for alkali treated peels. PMID- 27382622 TI - Juvenile Hormone Biosynthesis in Insects: What Is New, What Do We Know, and What Questions Remain? AB - Our understanding of JH biosynthesis has significantly changed in the last years. In this review I would like to discuss the following topics: (1) the progresses in understanding the JH biosynthesis pathway. Access to genome sequences has facilitated the identification of all the genes encoding biosynthetic enzymes and the completion of comprehensive transcriptional studies, as well as the expression and characterization of recombinant enzymes. Now the existence of different flux directionalites, feed-back loops and pathway branching points in the JH biosynthesis pathways can be explored; (2) the new concepts in the modulation of JH synthesis by allatoregulators. The list of putative JH modulators is increasing. I will discuss their possible role during the different physiological states of the CA; (3) the new theoretical and physiological frameworks for JH synthesis analysis. I will discuss the bases of the flux model for JH biosynthesis. JH plays multiple roles in the control of ovary development in female mosquitoes; therefore, the CA presents different physiological states, where JH synthesis is altered by gating the flux at distinctive points in the pathway; (4) in the final section I will identify new challenges and future directions on JH synthesis research. PMID- 27382626 TI - Determination of Accuracy of Fetal Weight Using Ultrasound and Clinical Fetal Weight Estimations in Calabar South, South Nigeria. AB - Information on fetal weight is of importance to obstetricians in the management of pregnancy and delivery. The objective of this study is to compare the accuracy of clinical and sonographic methods of predicting fetal weights at term. This prospective comparative study of 200 parturients was conducted at the University of Calabar Teaching Hospital, Calabar. The study participants were mothers with singleton term pregnancy admitted for delivery. The mean absolute percentage errors of both clinical and ultrasound methods were 11.16% +/- 9.48 and 9.036% +/ 7.61, respectively, and the difference was not statistically significant (P = 0.205). The accuracy within 10% of actual birth weights was 69.5% and 72% for both clinical estimation of fetal weight and ultrasound, respectively, and the difference was not statistically significant (P = 0.755). The accuracy of fetal weight estimation using Dare's formula is comparable to ultrasound estimates for predicting birth weight at term. PMID- 27382625 TI - Attitude and Knowledge of Indian Emergency Care Residents towards Use of Proton Pump Inhibitors. AB - Objective. Several studies carried out in developed countries have reported disproportionately high usage of acid suppressive drugs, especially proton pump inhibitors (PPIs). However, systematic assessment of attitude and practices of health care providers towards the use of these drugs in developing countries is lacking. In this study, we assessed the knowledge, attitude, and preferences of resident doctors posted in the emergency department of a tertiary care hospital in North India, towards the use of PPIs. Methods. A questionnaire based survey was carried out. Results. Fifty resident doctors responded to the questionnaire. Thirty-six percent reported prescribing acid suppressive drugs for majority of their patients, while 12% prescribed them to almost all patients they attended. Acute gastritis was the most common indication for prescribing PPI/H2 blockers (50%). The majority of respondents (92%) regarded PPIs as their first choice in acid suppressive agents and 58% administered it through intravenous route. Knowledge about PPI related adverse effects was low. Conclusions. Emergency care residents in India also tend to overuse PPIs in a manner similar to their counterparts in developed countries. Specific measures may be helpful in preventing such practices. PMID- 27382627 TI - Ensemble Nonlinear Autoregressive Exogenous Artificial Neural Networks for Short Term Wind Speed and Power Forecasting. AB - Short-term wind speed and wind power forecasts (for a 72 h period) are obtained using a nonlinear autoregressive exogenous artificial neural network (ANN) methodology which incorporates either numerical weather prediction or high resolution computational fluid dynamics wind field information as an exogenous input. An ensemble approach is used to combine the predictions from many candidate ANNs in order to provide improved forecasts for wind speed and power, along with the associated uncertainties in these forecasts. More specifically, the ensemble ANN is used to quantify the uncertainties arising from the network weight initialization and from the unknown structure of the ANN. All members forming the ensemble of neural networks were trained using an efficient particle swarm optimization algorithm. The results of the proposed methodology are validated using wind speed and wind power data obtained from an operational wind farm located in Northern China. The assessment demonstrates that this methodology for wind speed and power forecasting generally provides an improvement in predictive skills when compared to the practice of using an "optimal" weight vector from a single ANN while providing additional information in the form of prediction uncertainty bounds. PMID- 27382628 TI - Hahn Sequence Space of Modals. AB - The history of modal intervals goes back to the very first publications on the topic of interval calculus. The modal interval analysis is used in Computer graphics and Computer Aided Design (CAD), namely, the computation of narrow bounds on Bezier and B-Spline curves. Since modal intervals are used in many fields, we introduce a new sequence space h(gI) called the Hahn sequence space of modal intervals. We have given some new definitions and theorems. Some inclusion relation and some topological properties of this space are investigated. Also dual spaces of this space are computed. PMID- 27382629 TI - Simultaneous Estimation of Four Antitussive Components from Herbal Cough Syrup by HPTLC. AB - A new simple, rapid, selective and precise high performance thin layer chromatographic (HPTLC) method has been developed for simultaneous estimation of vasicine, glycyrrhizin, eugenol, and cineole in herbal cough syrup. The retention factors of vasicine, glycyrrhizin, eugenol, and cineole are 0.53, 0.44, 0.75, and 0.77, respectively. Chromatography was performed on 60F254 percolated TLC plate using n-hexane : ethyl acetate : glacial acetic acid (8.5 : 1.0 : 0.5 v/v/v). Methods are validated according to ICH guidelines and can be adopted for the routine analysis of vasicine, glycyrrhizin, eugenol and cineole in herbal cough syrup. PMID- 27382630 TI - An Experimental Approach for Optimizing Coating Parameters of Electroless Ni-P-Cu Coating Using Artificial Bee Colony Algorithm. AB - This paper aims to present an experimental investigation for optimum tribological behavior (wear depth and coefficient of friction) of electroless Ni-P-Cu coatings based on four process parameters using artificial bee colony algorithm. Experiments are carried out by utilizing the combination of three coating process parameters, namely, nickel sulphate, sodium hypophosphite, and copper sulphate, and the fourth parameter is postdeposition heat treatment temperature. The design of experiment is based on the Taguchi L27 experimental design. After coating, measurement of wear and coefficient of friction of each heat-treated sample is done using a multitribotester apparatus with block-on-roller arrangement. Both friction and wear are found to increase with increase of source of nickel concentration and decrease with increase of source of copper concentration. Artificial bee colony algorithm is successfully employed to optimize the multiresponse objective function for both wear depth and coefficient of friction. It is found that, within the operating range, a lower value of nickel concentration, medium value of hypophosphite concentration, higher value of copper concentration, and higher value of heat treatment temperature are suitable for having minimum wear and coefficient of friction. The surface morphology, phase transformation behavior, and composition of coatings are also studied with the help of scanning electron microscopy, X-ray diffraction analysis, and energy dispersed X-ray analysis, respectively. PMID- 27382632 TI - Effect of Suction/Injection on Unsteady Hydromagnetic Convective Flow of Reactive Viscous Fluid between Vertical Porous Plates with Thermal Diffusion. AB - An investigation is performed to study the effect of suction/injection on unsteady hydromagnetic natural convection flow of viscous reactive fluid between two vertical porous plates in the presence of thermal diffusion. The partial differential equations governing the flow have been solved numerically using semi implicit finite-difference scheme. For steady case, analytical solutions have been derived using perturbation series method. Suction/injection is used to control the fluid flow in the channel, and an exothermic chemical reaction of Arrhenius kinetic is considered. Numerical results are presented graphically and discussed quantitatively with respect to various parameters embedded in the problem. PMID- 27382631 TI - Development and Validation of Sleep Disturbance Questionnaire in Patients with Acute Coronary Syndrome. AB - Background and Objectives. Severe sleep disturbance is a common problem among patients in cardiac care units (CCUs). There are questionnaires to measure sleep disturbances. Therefore, the present study seeks to design a valid and reliable questionnaire to assess sleep disturbance in patients with acute coronary syndrome (ACS) hospitalized in CCUs. Materials and Methods. In the present methodological research, items of the questionnaire were extracted through a systematic review. The validity and reliability of the questionnaires was assessed by face validity, content validity, construct validity, Cronbach's alpha coefficient, and test-retest methods. Results. Factor analysis provided a questionnaire of 23 items on 5 dimensions of sleep disturbance in coronary patients: "sleep onset and continuity disorder," "disorder in daytime functioning," "sleep disturbance caused by environmental factors," "sleep disturbance as a result of cardiac diseases," and "respiratory disorders during sleep." Furthermore, test-retest analysis showed a reliability correlation coefficient of r = 0.766 and alpha Cronbach's reliability (alpha = 0.855). Conclusion. Sleep disturbance questionnaire for patients with ACS hospitalized in coronary care unit (CCU) was identified in 5 dimensions and assessed for validity and reliability. To control and improve the sleep quality of CCU hospitalized patients, we need to identify and remove predisposing factors. PMID- 27382633 TI - Effects of Modulation Techniques (Manchester Code, NRZ or RZ) on the Operation of Hybrid WDM/TDM Passive Optical Networks. AB - In this paper, the performance and feasibility of a hybrid wavelength division multiplexing/time division multiplexing passive optical network (WDM/TDM PON) system with 128 optical network units (ONUs) is analysed. In this system, triple play services (video, voice and data) are successfully communicated through a distance of up to 28 km. Moreover, we analysed and compared the performance of various modulation formats for different distances in the proposed hybrid WDM/TDM PON. NRZ rectangular emerged as the most appropriate modulation format for triple play transmission in the proposed hybrid PON. PMID- 27382634 TI - Phenolic Acids (Gallic and Tannic Acids) Modulate Antioxidant Status and Cisplatin Induced Nephrotoxicity in Rats. AB - Cisplatin (cis-diamminedichloroplatinum (II) or CDDP), used in the treatment of many solid-tissue cancers, has its chief side-effect in nephrotoxicity. Hence, this study sought to investigate and compare the protective effect of gallic acid (GA) and tannic acid (TA) against cisplatin induced nephrotoxicity in rats. The rats were given a prophylactic treatment of GA and TA orally at a dose of 20 and 40 mg/kg body weight for 7 consecutive days before the administration of a single intraperitoneal (i.p.) injection of cisplatin (CP) at 7.5 mg/kg bwt. The protective effects of both GA and TA on CP induced nephrotoxicity were investigated by assaying renal function, oxidative stress biomarkers, and histopathological examination of kidney architecture. A single dose of cisplatin (7.5 mg/kg bwt) injected i.p. caused a significant increase in some biomarkers of renal function (creatinine, uric acid, and urea levels), with a marked elevation in malondialdehyde (MDA) content accompanied by a significant (P < 0.05) decrease in reduced glutathione (GSH) content (103.27%) of kidney tissue as compared to control group. Furthermore, a significant (P < 0.05) reduction in kidney antioxidant enzymes (SOD, catalase, GPx, and GST) activity was observed. However, pretreatment with oral administration of tannic acid and gallic acid at a dose of 20 and 40 mg/kg body weight, respectively, for 7 days prior to cisplatin administration reduced histological renal damage and suppressed the generation of ROS, lipid peroxidation, and oxidative stress in kidney tissues. These results indicate that both gallic and tannic acids could serve as a preventive strategy against cisplatin induced nephrotoxicity. PMID- 27382635 TI - Urinary Continence Outcomes after Puboprostatic Ligament Preserving Open Retropubic Radical Prostatectomy at a Sub-Saharan Hospital. AB - Background. Open retropubic radical prostatectomy is a commonly performed procedure for clinically localized prostate cancer. The demand for high level functional outcomes after therapy is increasing especially for young age patients; in this regard refinements in the surgical technique have been made. There is limited data to show the success of some of these refinements in resource limited settings. Methods. A retrospective clinical study was performed over a 2-year period at Mengo Hospital, Urology Unit. Men with clinically localized prostate cancer and who consented to the procedure were eligible and were recruited. Consequently excluded were those that turned out to have advanced disease and those with severe comorbidities. Patients were followed up for 3 months after surgery. Data was entered using SPSS version 17 and analyzed. Results. A total of 24 men with clinically localized prostate cancer underwent open retropubic puboprostatic ligament preserving radical prostatectomy technique. Mean age was 66, range 54-75 years. Outcome. Two patients had stress incontinence and three were incontinent at 3 months. The urinary continence recovery rate was 19/24 (79%) at 3 months. Conclusion. Preservation of the puboprostatic ligament in open retropubic radical prostatectomy was associated with rapid and a high rate of return to urinary continence among men with clinically localized disease. PMID- 27382636 TI - Exchange Transfusion for Neonatal Hyperbilirubinemia in Johannesburg, South Africa, from 2006 to 2011. AB - Background. Severe hyperbilirubinaemia requiring exchange transfusion has become less common in recent years; however, kernicterus still occurs. The aim of this study was to review babies undergoing exchange transfusion for severe hyperbilirubinaemia in a Johannesburg hospital. Methodology. This was a retrospective review of babies who required exchange transfusion in both the neonatal and the paediatric wards from June 1, 2006, to December 31, 2011. Results. There were 64 patients who underwent 67 exchange transfusions. Isoimmune haemolysis (both Rh and ABO incompatibility) was the cause of jaundice in 9/64 (14%). Most babies who underwent exchange transfusion were sick or preterm and were admitted in hospital after birth (38/64; 59.5%); three of these babies died, but not during the exchange transfusion (3/38; 7.9%); all three had signs suggestive of neonatal sepsis. The remaining 26 babies (40.6%) were readmitted to the paediatric wards for exchange transfusion. Six of these babies (6/26; 23.0%) had signs of kernicterus. The most significant complication of exchange transfusion was apnoea requiring mechanical ventilation in three patients (3/64; 4.6%). Conclusion. Despite a relatively low number of babies undergoing exchange transfusion, kernicterus still occurs and must be prevented. Proper protocols for screening and management of severe hyperbilirubinaemia need to be enforced. PMID- 27382637 TI - Guidelines for Reporting Medical Research: A Critical Appraisal. AB - As a response to a low quality of reporting of medical research, guidelines for several different types of study design have been developed to secure accurate reporting and transparency for reviewers and readers from the scientific community. Herein, we review and discuss the six most widely accepted and used guidelines: PRISMA, CONSORT, STROBE, MOOSE, STARD, and SPIRIT. It is concluded that the implementation of these guidelines has led to only a moderate improvement in the quality of the reporting of medical research. There is still much work to be done to achieve accurate and transparent reporting of medical research findings. PMID- 27382639 TI - Dynamic Response of a Rigid Pavement Plate Based on an Inertial Soil. AB - This work presents the dynamic response of a pavement plate resting on a soil whose inertia is taken into account in the design of pavements by rational methods. Thus, the pavement is modeled as a thin plate with finite dimensions, supported longitudinally by dowels and laterally by tie bars. The subgrade is modeled via Pasternak-Vlasov type (three-parameter type) foundation models and the moving traffic load is expressed as a concentrated dynamic load of harmonically varying magnitude, moving straight along the plate with a constant acceleration. The governing equation of the problem is solved using the modified Bolotin method for determining the natural frequencies and the wavenumbers of the system. The orthogonal properties of eigenfunctions are used to find the general solution of the problem. Considering the load over the center of the plate, the results showed that the deflections of the plate are maximum about the middle of the plate but are not null at its edges. It is therefore observed that the deflection decreased 18.33 percent when the inertia of the soil is taken into account. This result shows the possible economic gain when taking into account the inertia of soil in pavement dynamic design. PMID- 27382638 TI - Effectiveness of a Nutrition Education Program to Improve Children's Chewing Habits. AB - This quasi-experimental study determined whether the nutrition education program we developed to promote chewing food properly influenced children's chewing habits successfully. Four kindergarten classes in Japan (150 children, aged 5-6 years) were studied; one class received the educational program in the classroom and at home (Group A) and three classes received the program in the classroom only (Group B). The educational program was integrated into the classes' daily curriculum for five weeks. It included storytelling with large picture books, chewing consciously while eating lunch, singing a song with gestures, and greetings before and after meals (both groups). Group A also used a paper textbook and was provided information by the leaflet to encourage guardians to implement the program at home. Chewing habits before and after intervention were evaluated: (1) guardians completed seven questionnaire items related to chewing habits and chewing movement and (2) the number of chews and time spent eating the test meal were measured by a portable chewing sensor. Both approaches improved the children's chewing habits; however, no difference was found between the two groups. We concluded that this intervention could be used to improve chewing habits in young children even without active involvement of their guardians. PMID- 27382640 TI - Control of Drug Dissolution Rate from Film Dosage Forms Containing Valsartan. AB - Film dosage forms (FDs) containing valsartan (VST), a popular antihypertensive drug, were prepared using a casting method with sodium alginate and other polysaccharides as the film base. Drug dissolution profiles of the FDs were investigated in limited medium. The FDs were 170-200 MUm thick and were easy to handle. All FDs immediately swelled and disintegrated in the medium. About 23% of the VST incorporated into the FD prepared with 1.5% sodium alginate dissolved at 5 min. The initial dissolution rate of VST increased upon the addition of chitosan to the film base; this effect was not observed in the case of chitin. On the other hand, the rate apparently decreased upon modification with alginic acid. In addition, the solubility of VST in the dissolution medium was changed by the addition of chitosan or alginic acid. FDs prepared with polysaccharides are useful for simplifying the administration of drugs to patients, and the drug dissolution rate from FDs can be controlled by modification. PMID- 27382641 TI - Health Risk Assessment of Heavy Metals in Traditional Cosmetics Sold in Tunisian Local Markets. AB - This study was undertaken in order to determine heavy metal contents in twelve (n = 12) henna brands and eleven (n = 11) kohl products. An analytical test was performed for Pb, Cd, Cu, and Zn in henna and kohl products using atomic absorption spectrophotometery. The overall mean concentrations of heavy metals in henna varied between 1.2 and 8.9 MUg g(-1) for Pb; 0.8 and 18.6 MUg g(-1) for Cd; 0.5 MUg g(-1) and 3.3 MUg g(-1) for Cu; and 3.7 MUg g(-1) and 90.0 MUg g(-1) for Zn. As for kohl products, Pb concentrations ranged between 51.1 MUg g(-1) and 4839.5 MUg g(-1), Cd concentrations ranged between 1.0 MUg g(-1) and 158.6 MUg g( 1), Cu concentrations ranged between 2.5 MUg g(-1) and 162.5 MUg g(-1), and Zn concentrations ranged between 0.7 MUg g(-1) and 185.0 MUg g(-1). The results of our study revealed that Pb, Cd, Cu, and Zn contents in investigated samples were high, making from the prolonged use of such products a potential threat to human health. Therefore, major quality controls are recommended in order to enforce acceptable limits of potential contaminants in cosmetics and good manufacturing practice. PMID- 27382642 TI - Appraisals of Bangladeshi Medicinal Plants Used by Folk Medicine Practitioners in the Prevention and Management of Malignant Neoplastic Diseases. AB - Cancer is a group of diseases which is categorized to differentiate into diverse cell types and move around in the body to sites of organogenesis that is key to the process of tumor genesis. All types of cancer fall into the group of malignant neoplastic diseases. In Bangladesh, cancer is now one of the foremost killer diseases and its personal, social, and economic bearing are huge. Plant derived natural compounds (vincristine, vinblastine, etoposide, paclitaxel, camptothecin, topotecan, and irinotecan) are useful for the treatment of cancer. Since there is no extensive ethnobotanical research study in Bangladesh regarding the traditional uses of medicinal plants against neoplasms, therefore, a randomized ethnopharmacological surveys were carried out in 3 districts of Bangladesh to learn more about the usage of anticancer medicinal plants and their chemical constituents having antineoplastic activity. Comprehensive interviews were conducted to the folk medicine practitioners and medicinal plants as pointed out by them were photographed, collected, deposited, and identified at the Bangladesh National Herbarium. The various plant parts have been used by the healers which included whole plant, leaves, fruits, barks, roots, and seeds. This study evaluated considerable potential for discovery of novel compounds with less side effects in the management and prevention of malignancy in cancer. PMID- 27382643 TI - Prevalence and Perspectives of Complementary and Alternative Medicine among University Students in Atlanta, Newcastle upon Tyne, and New Delhi. AB - Objective. A cross-cultural comparative study was developed that surveyed university students in Atlanta (United States), New Delhi (India), and Newcastle upon Tyne (United Kingdom) to understand the prevalence and perspectives of CAM in three urban societies with different healthcare systems. Design. Surveys were sent to students in the three aforementioned cities. Survey distribution occurred over 6 months from May to November 2015. A total of 314 surveys were received. Results. Dietary and vitamin supplements had the highest prevalence collectively (n = 203), followed by meditation, yoga, and massage. Commentary analysis showed the importance of science and evidence in justifying CAM practice. Conclusions. Matching the most prevalent practices with their designated NCCAM categories suggested that the students were attracted to biologically based, body-based, and mind-body practices as the central themes of attraction. Selected and prevalent CAM practices suggested the students' desire to maintain physical and mental fitness. Access to healthcare may have influence on the prevalence of CAM. Indian students were more likely to view CAM as a viable alternative to conventional medicine. PMID- 27382644 TI - Nursing in Ghana: A Search for Florence Nightingale in an African City. AB - Nursing in Ghana is a crucial subject that permeates almost every issue in the society especially the field of hospital care. To a large extent, the frontiers of nursing have expanded since the time of Florence Nightingale. Globally some studies have been done to study nursing icons like her. The values in nursing practice however continue to preoccupy our minds. The need to accentuate the gains made by historical figures in nursing in present times as well as the nature of interactions between practitioners and patients continues to be of paramount concern to many across the globe and Ghana in particular. This study does an analysis of existing literature on Florence Nightingale and the nature of nursing in Ghana from the colonial times. Additionally, it analyzes responses concerning the activities of nurses and their interactions with patients in Kumasi. The varied information has been thematically pieced together to make inferences that are of great interest to nursing practitioners, policy makers, administrators, and educators among others. The findings to the study suggest among other things that the challenges faced by the nursing institution in modern times are similar to those of the earlier period. The study calls for the emulation of the positive ideas of Florence Nightingale to promote the interest of patients, a core objective championed by a revered nurse. PMID- 27382646 TI - Genetic polymorphism of CSN2 gene in Banat White and Carpatina goats. AB - The main objective of the current study was to obtain preliminary results on genetic polymorhism of A and C variants at the CSN2 locus in indigenous Romanian goat (Banat White, Carpatina) breeds using a rapid and efficient genotyping method, TaqMan assay (Applied Biosystems, USA). Hair follicle samples were taken from 73 Banat White and 82 Carpatina purebred goats from Arad, Caras-Severin and Timis counties. After the optimization of the genotyping assay it was found that the most frequent allele at the CSN2 locus was C in Banat White breed, while CSN2*A and CSN2*C showed similar frequencies in Carpatina breed (0.51 and 0.49, respectively). All three genotypes were detected in the two studied breeds, however, AA was the least frequent, especially in Banat White. The studied polymorphisms are potential markers for milk production in the studied breeds and the results will be useful in future works aimed at identifying possible associations with milk production traits, in order to test the feasibility of producing hypoallergenic organic goat milk. PMID- 27382645 TI - Systemically administered AAV9-sTRAIL combats invasive glioblastoma in a patient derived orthotopic xenograft model. AB - Adeno-associated virus (AAV) vectors expressing tumoricidal genes injected directly into brain tumors have shown some promise, however, invasive tumor cells are relatively unaffected. Systemic injection of AAV9 vectors provides widespread delivery to the brain and potentially the tumor/microenvironment. Here we assessed AAV9 for potential glioblastoma therapy using two different promoters driving the expression of the secreted anti-cancer agent sTRAIL as a transgene model; the ubiquitously active chicken beta-actin (CBA) promoter and the neuron specific enolase (NSE) promoter to restrict expression in brain. Intravenous injection of AAV9 vectors encoding a bioluminescent reporter showed similar distribution patterns, although the NSE promoter yielded 100-fold lower expression in the abdomen (liver), with the brain-to-liver expression ratio remaining the same. The main cell types targeted by the CBA promoter were astrocytes, neurons and endothelial cells, while expression by NSE promoter mostly occurred in neurons. Intravenous administration of either AAV9-CBA-sTRAIL or AAV9-NSE-sTRAIL vectors to mice bearing intracranial patient-derived glioblastoma xenografts led to a slower tumor growth and significantly increased survival, with the CBA promoter having higher efficacy. To our knowledge, this is the first report showing the potential of systemic injection of AAV9 vector encoding a therapeutic gene for the treatment of brain tumors. PMID- 27382647 TI - Screening and characterization of thermo-active enzymes of biotechnological interest produced by thermophilic Bacillus isolated from hot springs in Tunisia. AB - As part of the contribution to the global efforts in research of thermostable enzymes being of industrial interest, we focus on the isolation of thermophilic bacteria from Tunisian hot springs. Among the collection of 161 strains of thermophilic Bacillus isolated from different samples of thermal water in Tunisia, 20% are capable of growing at 100 degrees C and the rest grow at 70 degrees C or above. Preliminary activity tests on media supplemented with enzyme substrates confirmed that 35 strains produced amylases, 37 - proteases, 43 - cellulases, 31 - xylanases and 37 - mannanases. The study of the effect of temperature on enzyme activity led to determination of the optimal temperatures of activities that vary between 60 and 100 degrees C. Several enzymes were active at high temperatures (80, 90 and 100 degrees C) and kept their activity even at 110 degrees C. Several isolated strains producing enzymes with high optimal temperatures of activity were described for the first time in this study. Both strains B62 and B120 are producers of amylase, protease, cellulase, xylanase, and mannanase. The sequencing of 16S DNA identified isolated strains as Geobacillus kaustophillus, Aeribacillus pallidus, Geobacillus galactosidasus and Geobacillus toebii. PMID- 27382648 TI - Toward Integration of STD, HIV, TB, and Viral Hepatitis Surveillance. PMID- 27382649 TI - Practical Considerations for Matching STD and HIV Surveillance Data with Data from Other Sources. AB - Data to guide programmatic decisions in public health are needed, but frequently epidemiologists are limited to routine case report data for notifiable conditions such as sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV). However, case report data are frequently incomplete or provide limited information on comorbidity or risk factors. Supplemental data often exist but are not easily accessible, due to a variety of real and perceived obstacles. Data matching, defined as the linkage of records across two or more data sources, can be a useful method to obtain better or additional data, using existing resources. This article reviews the practical considerations for matching STD and HIV surveillance data with other data sources, including examples of how STD and HIV programs have used data matching. PMID- 27382650 TI - Trends in Neisseria gonorrhoeae Incidence Among HIV-Negative and HIV-Positive Men in Washington State, 1996-2007. AB - OBJECTIVES: We assessed population-level trends in human immunodeficiency virus (HIV) and Neisseria gonorrhoeae co-infection among adult males in Washington State between 1996 and 2007. METHODS: Population-based categorical disease surveillance registries for gonorrhea and for HIV were electronically matched and merged at the record level and incidence rates were calculated for reported HIV positive and presumed HIV-negative men. RESULTS: The incidence of gonorrhea infection increased significantly among both HIV-positive and presumed HIV negative men from 1996 to 2005, and this trend has recently reversed for both groups. The annual incidence rate of gonorrhea among HIV-positive men was found to be higher in all years than among men presumed to be HIV-negative. CONCLUSIONS: Inequality in the burden of gonorrhea by HIV-infection status suggests continuing sexual risk-taking among HIV-positive men as well as possible barriers to diagnosis, treatment, and partner services. This inequality may also reflect significant differences in gonorrhea burden among men who have sex with men as well as by HIV status. Monitoring emergent secular trends in population level HIV/sexually transmitted infection comorbidity through registry matching is an achievable strategy for developing an evidence base to inform program collaboration and service integration efforts aimed at providing more comprehensive disease prevention services. PMID- 27382651 TI - Assessment of the Association of Chlamydia trachomatis Infection and Adverse Perinatal Outcomes with the Use of Population-Based Chlamydia Case Report Registries and Birth Records. AB - OBJECTIVE: We assessed the relationship between Chlamydia trachomatis (CT) infections identified during pregnancy and adverse perinatal birth outcomes (including premature rupture of membranes, preterm delivery, and low birthweight) by matching CT reports and birth records. METHODS: We merged California birth records from 1997, 1998, and 1999 with California CT reports from the same years to determine the proportion of birth records matched to a female CT report, using maternal last name, first name, date of birth, and county of residence. We used logistic regression to assess the crude and adjusted association between a CT report less than 10 months before the birth record date and premature rupture of membranes, preterm delivery, and low birthweight. These results were adjusted for age, race/ethnicity, level of education, and prenatal care. RESULTS: Of 675,786 birth records and 101,296 female CT reports, 14,039 women had a CT case report and a birth record; 10,917 birth records (1.6%) were matched to a CT report during pregnancy, and 10,940 (10.8%) of CT reports were matched to a birth record date 10 months after date of diagnosis/report. For premature rupture of membranes, the adjusted odds ratio (AOR) was 1.2, 95% confidence interval (CI) 1.0, 1.3; for low birthweight, the AOR was 1.2, 95% CI 1.1, 1.3. The reduction in birthweight associated with prenatal CT infection was 31.7 grams. CONCLUSIONS: The increased risk of adverse perinatal outcomes associated with prenatal CT infection supports current prenatal CT screening guidelines. Matching of surveillance and vital statistics data sources was an efficient method to assess this association. PMID- 27382652 TI - Integration of Surveillance for STDs, HIV, Hepatitis, and TB: A Survey of U.S. STD Control Programs. AB - OBJECTIVES: Integration of surveillance for sexually transmitted diseases (STDs), human immunodeficiency virus (HIV), hepatitis, and tuberculosis (TB) may improve disease prevention and control. We determined the extent of surveillance integration in these programs, the benefits of integration, and barriers to increased integration. METHODS: We e-mailed a survey to the 58 federally funded local and state STD control programs and followed up with phone interviews of nine program representatives. RESULTS: The response rate was 81%. Many had compared infections by population subgroup for STDs and HIV (89%), STDs and hepatitis (53%), or STDs and TB (28%). Most (74%) had examined co-infections with HIV and STDs at the individual level and entered STD and HIV surveillance data into the same database (54%). All respondents thought some integration would be useful. Many (72%) used integrated data to disseminate information or change program strategies. The most commonly reported barriers to integration were policies preventing work with HIV data (85%) and incompatible databases (59%). CONCLUSIONS: Most STD control programs in the United States have some experience integrating surveillance data, but the degree of integration varies widely. Specific barriers to further integration were identified. The Centers for Disease Control and Prevention can help address these barriers by facilitating access to information and sharing technical solutions. Local and state programs can continue advancing surveillance integration by improving understanding of where integrated data are needed, increasing the use of available data, and pressing for appropriate and secure data sharing. PMID- 27382653 TI - Identifying Challenges to the Integration of Computer-Based Surveillance Information Systems in a Large City Health Department: A Case Study. AB - OBJECTIVE: Integrated infectious disease surveillance information systems have the potential to provide important new surveillance capacities and business efficiencies for local health departments. We conducted a case study at a large city health department of the primary computer-based infectious disease surveillance information systems during a 10-year period to identify the major challenges for information integration across the systems. METHODS: The assessment included key informant interviews and evaluations of the computer based surveillance information systems used for acute communicable diseases, human immunodeficiency virus/acquired immunodeficiency syndrome, sexually transmitted diseases, and tuberculosis. Assessments were conducted in 1998 with a follow-up in 2008. Assessments specifically identified and described the primary computer-based surveillance information system, any duplicative information systems, and selected variables collected. RESULTS: Persistent challenges to information integration across the information systems included the existence of duplicative data systems, differences in the variables used to collect similar information, and differences in basic architecture. CONCLUSIONS: The assessments identified a number of challenges for information integration across the infectious disease surveillance information systems at this city health department. The results suggest that local disease control programs use computer based surveillance information systems that were not designed for data integration. To the extent that integration provides important new surveillance capacities and business efficiencies, we recommend that patient-centric information systems be designed that provide all the epidemiologic, clinical, and research needs in one system. In addition, the systems should include a standard system of elements and fields across similar surveillance systems. PMID- 27382654 TI - Charting a Path to Location Intelligence for STD Control. AB - This article describes the New York State Department of Health's GeoDatabase project, which developed new methods and techniques for designing and building a geocoding and mapping data repository for sexually transmitted disease (STD) control. The GeoDatabase development was supported through the Centers for Disease Control and Prevention's Outcome Assessment through Systems of Integrated Surveillance workgroup. The design and operation of the GeoDatabase relied upon commercial-off-the-shelf tools that other public health programs may also use for disease-control systems. This article provides a blueprint of the structure and software used to build the GeoDatabase and integrate location data from multiple data sources into the everyday activities of STD control programs. PMID- 27382655 TI - Assessment of Geographic Information Systems and Data Confidentiality Guidelines in STD Programs. AB - OBJECTIVE: Advancements in technology, such as geographic information systems (GIS), expand sexually transmitted disease (STD) program capacity for data analysis and visualization, and introduce additional confidentiality considerations. We developed a survey to examine GIS use among STD programs and to better understand existing data confidentiality practices. METHODS: A Web based survey of eight to 22 questions, depending on program-specific GIS capacity, was e-mailed to all STD program directors through the National Coalition of STD Directors in November 2004. Survey responses were accepted until April 15, 2005. RESULTS: Eighty-five percent of the 65 currently funded STD programs responded to the survey. Of those, 58% used GIS and 54% used geocoding. STD programs that did not use GIS (42%) identified lack of training and insufficient staff as primary barriers. Mapping, spatial analyses, and targeting program interventions were the main reasons for geocoding data. Nineteen of the 25 programs that responded to questions related to statistical disclosure rules employed a numerator rule, and 56% of those used a variation of the "Rule of 5." Of the 28 programs that responded to questions pertaining to confidentiality guidelines, 82% addressed confidentiality of GIS data informally. CONCLUSIONS: Survey findings showed the increasing use of GIS and highlighted the struggles STD programs face in employing GIS and protecting confidentiality. Guidance related to data confidentiality and additional access to GIS software and training could assist programs in optimizing use of spatial data. PMID- 27382656 TI - Improving Surveillance of Sexually Transmitted Diseases through Geocoded Morbidity Assignment. AB - OBJECTIVES: We assessed the added value of using a geocoder to improve sexually transmitted disease (STD) surveillance data and decision support through redistribution of inaccurately assigned morbidity in Richmond, Virginia. METHODS: Virginia initiated geocoding of STD data as a data quality tool in 2002. Geocoded output files were assessed and discordant proportions of reported gonorrhea and chlamydia morbidity were reassigned appropriately for the city of Richmond, Chesterfield County, and Henrico County (2002 to 2006). We used Chi-square analysis to compare assignment proportions and calculated crude odds ratios for 2006 data to estimate increased case reassignment likelihood. RESULTS: From 2002 to 2006, 149,229 cases of gonorrhea and chlamydia were reported within the Commonwealth of Virginia. Of the reported morbidity, 81% of cases (n=120,875) were successfully geocoded; 7% (n=8,461) of geocoded addresses were reassigned. Approximately 76% (n=6,412) of all reassigned cases occurred within Richmond and Chesterfield and Henrico counties. In 2006, 84% (n=654) of reassigned cases in this tri-city/county area were initially reported as Richmond morbidity. Data quality improvements reduced Richmond's artificially inflated morbidity by 18% and increased Chesterfield and Henrico morbidity by 17% and 55%, respectively. Richmond morbidity was three times more likely to be reassigned than Chesterfield cases (odds ratio [OR] = 2.93, 95% confidence interval [CI] 2.21, 3.90), and two times more likely than Henrico cases (OR=2.12, 95% CI 1.63, 2.76). Richmond's number one national rank for STD rates was reduced beginning in 2002. CONCLUSIONS: Declining rates of STDs were statistically associated with geocoded morbidity reassignments. Implementation of this data quality business process has improved epidemiologic analyses, prevention planning, and assessment of resource allocations. The reduction in Richmond's national STD rankings is indicative of the effect geocoding can have on surveillance data. PMID- 27382657 TI - Here Comes the SSuN: Early Experiences with the STD Surveillance Network. AB - In 2005, the Centers for Disease Control and Prevention established the STD Surveillance Network (SSuN), a sentinel surveillance system comprising local, enhanced sexually transmitted disease (STD) surveillance systems that follow common protocols. The purpose of SSuN is to improve the capacity of national, state, and local STD programs to detect, monitor, and respond rapidly to trends in STDs through enhanced collection, reporting, analysis, visualization, and interpretation of clinical, behavioral, and geographic information obtained from a geographically diverse sample of individuals diagnosed with STDs. To demonstrate the utility of a national sentinel surveillance network, this article reviews the lessons learned from the first three years of SSuN, which, through its enhanced gonorrhea and genital warts sentinel surveillance projects, has proved to be a useful adjunct to routine STD surveillance in the U.S. that can be expanded into other areas of STD public health interest. PMID- 27382658 TI - Providing Mailing Cost Reimbursements: The Effect on Reporting Timeliness of Sexually Transmitted Diseases in Virginia. AB - OBJECTIVES: We investigated the effect of providing mailing cost reimbursements to local health departments on the timeliness of the reporting of sexually transmitted diseases (STDs) in Virginia. METHODS: The Division of Disease Prevention, Virginia Department of Health, provided mailing cost reimbursements to 31 Virginia health districts from October 2002 to December 2004. The difference (in days) between the diagnosis date (or date the STD paperwork was initiated) and the date the case/STD report was entered into the STD surveillance database was used in a negative binomial regression model against time (as divided into three periods-before, during, and after reimbursement) to estimate the effect of providing mailing cost reimbursements on reporting timeliness. RESULTS: We observed significant decreases in the number of days between diagnosis and reporting of a case, which were sustained after the reimbursement period ended, in 25 of the 31 health districts included in the analysis. We observed a significant initial decrease (during the reimbursement period) followed by a significant increase in the after-reimbursement phase in one health district. Two health districts had a significant initial decrease, while one health district had a significant decrease in reporting timeliness in the period after reimbursement. Two health districts showed no significant changes in the number of days to report to the central office. CONCLUSION: Providing reimbursements for mailing costs was statistically associated with improved STD reporting timeliness in almost all of Virginia's health districts. Sustained improvement after the reimbursement period ended is likely indicative of improved local health department reporting habits. PMID- 27382659 TI - California Gonorrhea Surveillance System: Methodologic Aspects and Key Results of a Sample-Based System. AB - OBJECTIVES: This article describes findings from the California Gonorrhea Surveillance System (CGSS), developed in response to the need for detailed risk behavior data and clinical data required to control increasing gonorrhea (GC) infections in California. METHODS: CGSS is a sample-based surveillance system implemented throughout California in 2007. In 34 of 61 local health jurisdictions (LHJs), 10% of GC cases are sampled for interview; in the other 27 LHJs, all cases are followed. A standardized case investigation record collects case reported risk data and provider-reported clinical data, and is electronically prepopulated with available contact data. Exclusion criteria include age younger than 14 years, a GC diagnosis within the previous 30 days, and provider request that patient not be contacted. Analyses are weighted to account for sample design. RESULTS: In 2007, 31,192 cases of GC were reported in California. Of these, 5,388 were sampled for follow-up and 2,715 were interviewed, for a response rate of 54.2%. Of those interviewed, 49.6% were female, 28.8% were heterosexual males, and 21.6% were men who have sex with men (MSM). CGSS collects a wide range of behavioral and clinical data for targeted programmatic action. Findings from the 2007 CGSS included data on the following areas: incarceration (highest among heterosexual males [22.4%]); methamphetamine use (high overall [12.2%] and lower among African Americans [4.6%]); co-infection with human immunodeficiency virus (high among MSM [31.9%] and very low among heterosexual males and females [<0.5%]); and improper antibiotic use (8.3% overall; 25.6% among patients attending urgent care clinics). CONCLUSION: CGSS, an innovative sample-based surveillance system, is effective and flexible. The system provides actionable data on an ongoing basis. PMID- 27382660 TI - Use of a Business Approach to Improve Disease Surveillance Data Management Systems and Information Technology Process in Florida's Bureau of STD Prevention and Control. AB - The business of sexually transmitted disease (STD) prevention and control demands technology that is capable of supporting a wide array of program activities-from the processing of laboratory test results to the complex and confidential process involved in contact investigation. The need for a tool that enables public health officials to successfully manage the complex operations encountered in an STD prevention and control program, and the need to operate in an increasingly poor resource environment, led the Florida Bureau of STD to develop the Patient Reporting Investigation Surveillance Manager. Its unique approach, technical architecture, and sociotechnical philosophy have made this business application successful in real-time monitoring of disease burden for local communities, identification of emerging outbreaks, monitoring and assurance of appropriate treatments, improving access to laboratory data, and improving the quality of data for epidemiologic analysis. Additionally, the effort attempted to create and release a product that promoted the Centers for Disease Control and Prevention's ideas for integration of programs and processes. PMID- 27382661 TI - American College of Emergency Physicians takes issue with report from new HealthFacts RI database. PMID- 27382662 TI - World Trade Center Health Program; Addition of New-Onset Chronic Obstructive Pulmonary Disease and WTC-Related Acute Traumatic Injury to the List of WTC Related Health Conditions. Final rule. AB - The World Trade Center (WTC) Health Program conducted a review of published, peer reviewed epidemiologic studies regarding potential evidence of chronic obstructive pulmonary disease (COPD) and acute traumatic injury among individuals who were responders to or survivors of the September 11, 2001, terrorist attacks. The Administrator of the WTC Health Program (Administrator) found that these studies provide substantial evidence to support a causal association between each of these health conditions and 9/11 exposures. As a result, the Administrator is publishing a final rule to add both new-onset COPD and WTC-related acute traumatic injury to the List of WTC-Related Health Conditions eligible for treatment coverage in the WTC Health Program. PMID- 27382663 TI - Notes on Brazilian Cancer Registries. PMID- 27382664 TI - The Privilege of Being Invited In. PMID- 27382665 TI - Emily Alyssa Halpern Keram, MD: The Not So Accidental Forensic Psychiatrist. PMID- 27382666 TI - Intervention for advanced heart failure patients and their caregivers to support shared decision-making about implantation of a ventricular assist device. AB - This project aimed to co-develop and pilot an intervention plan to support shared decision-making (SDM) for patients considering a ventricular assist device (VAD), their caregivers and the health care team. The project involved a focus group with patients and caregivers to explore their decision-making needs along with regular participation in team meetings resulting in the creation of a decision aid. The decision aid answered needs expressed by patients and caregivers, as well as the team's initial needsfor informational support, optimization of information exchange and process standardization. A workshop on SDM was also conducted to increase competence toward this approach and the use of the decision aid. This project is timely and relevant given the increase in VAD implantation in Canada. The intervention could also be applicable to other decision-making situations in which active participation can improve the quality of the decision process. PMID- 27382668 TI - The Relationship between Posttraumatic Growth and Social Support in Patients with Myocardial Infarction. AB - The present study was conducted to examine the concept of post-traumatic growth (PTG) and its relationship with social support in patients with myocardial infarction. The study included 166 patients with myocardial infarction admitted to heart clinics in Bonab, Iran. Data were collected using the Post Traumatic Growth Inventory and the Clinical Social Support Scale. A positive, moderate relationship between social support and PTG (p<0.001; r=0.361) was found. Talking to others, providing tangible goods, and giving information about the disease may facilitate cognitive processing and adaptation, which, in turn, can lead to more PTG. Given the positive relationship between social support and PTG, nurses, families, and other sources of social support can provide emotional, instrumental and informational supports to increase positive psychological behaviours in patients with myocardial infarction. PMID- 27382667 TI - Development of the Prodromal Symptoms-Screening Scale (PS-SS): Preliminary Validity and Reliability. AB - Every 40 seconds a person dies of cardiovascular disease.Individuals do not recognize the warning signs--prodromalsymptoms--of an imminent myocardial ischemic event. TheProdromal Symptoms-Screening Scale (PS-SS) is a nine itemmeasure designed to evaluate PS in individuals with coronaryartery disease. AIM: This article reports onfour studies (systematic review,focusgroup study, content validity testing and factor analysis) that contributed to the development and psychometric examination ofthe PS-SS. RESULTS: PS experienced included: unusual fatigue, sleep disturbance, chest pain, anxiety, gastrointestinal symptoms andshortness of breath. The CVI derived was 0.85. The PS-SS presented a two-factor structure pertaining to Specific ProdromalSymptoms and Non-Specific Prodromal Symptoms. Internal consistency reliability was 0.61. CONCLUSIONS: The PS-SS reflects current prodromal literature,clinical practice and ACS patients' experiences of PS. Furtheritem generation, clarity of symptom description and psychometricevaluation needs to occur prior to use in clinical practice.Keywords: prodromal symptoms, acute coronarysyndrome, psychometric testing, tool development PMID- 27382669 TI - Exploring the Perceptions and Health Behaviours of Patients Following an Elective Ad-hoc Percutaneous Coronary Intervention: A Qualitative Study. AB - RESULTS: Participants expressed uncertainty about their future health and feared disease recurrence, which appeared to provide motivation for adopting a healthier lifestyle. Although two participants voiced the belief that the elective PCI cured their disease, this perception did not appear to influence their engagement in risk reduction behaviours. However, systemfactors such as a lack of information, direction, and/or support from health care providers appeared to play a limiting role in their ability to move forward with lifestyle change. BACKGROUND: Elective ad-hoc percutaneous coronary interventions (PCIs) are increasingly used to manage the symptoms of coronary artery disease (CAD). However, we have limited understanding of the patients' experiences and health behaviours post-procedure. PURPOSE: Explore the factors that influence the perceptions and health behaviours of patients after elective ad-hoc PCI. METHODS: This interpretive descriptive study used purposive sampling to recruit participants (N = 10) aged 44 to 65 years following an elective ad-hoc PCI from a cardiac catheterization laboratory at a tertiary centre in Winnipeg, MB. Participants were interviewed 11 to 35 days following their procedure. Recruitment continued until no new substantive themes emerged. The Health Belief Model provided the frameworkfor developing, exploring, interpreting, and analyzing the data. PRACTICE IMPLICATIONS: Nurses have a key role in the education of patients and in providingpatient-centred care that supports lifestyle change. Nurses need to develop strategies that decrease barriers to engaging in risk reduction behaviours following elective ad-hoc PCI if patients are to experience improved health and longevity. PMID- 27382670 TI - [No available]. AB - In the area of cardiac rehabilitation, little attention has been given to phase III (maintenance phase), as compared to phase II (rehabilitation phase). Studies on the maintenance phase have highlighted the importance of maintaining the newly acquired healthy living habits in order to continue benefitting from them and prevent the recurrence of cardiovascular diseases and mortality. However, these studies have revealed disturbing dropout rates, from 25 to 50%. There is little research on the factors associated with the maintenance of the new healthy living habits after completing phase II of a cardiac rehabilitation program. This study innovates by measuring riskfactors and quality of life, as predictors of exercise maintenance. The goal of this project is to verify which variables are linked to the maintenance of physical activity during phase III. The sample of the study is composed of 529 patients who completed, between 2005 and 2012, phase II of the cardiac rehabilitation program, called Coeur en sant, offered by the Universite de Moncton. The main results show that patients at risk of not maintaining their physical activity are younger, male, with only afew risk factors and a lower score on the quality of physical life scale, particularly with respect to the physical role and general health components. PMID- 27382671 TI - [Progress in diagnosis and treatment of benign paroxysmal positional vertigo]. PMID- 27382672 TI - [Expression of p53, p21, PCNA and COX-2 and its relationship with recurrence in the early-stage laryngeal cancer with negative surgical margin]. AB - OBJECTIVE: To explore the relation between the expression of p53, p21, PCNA and COX-2 and local recurrence in resection margins of laryngeal carcinoma operation. METHOD: SElect 98 patients with laryngeal carcinoma, who came to our hospital from Nov, 2005 to Dec, 2010. Diagnosed with early laryngeal squamous cell carcinoma by a pathological examination, all these patients received CO2 laser surgery to cut the entire tumors. Keep the primary lesion and resection margin tissues after that and take 5 mm peritumoral tissue as a sample of operation resection margin. With the chemical method of SP, record in detail the local recurrence condition by clinical diagnosis every 3-6 months or telephone follow up for 2 years. RESULT: (1)The positive rate of p53, p21, PCNA and COX-2 in the tumor tissues of the 98 patients with laryngeal carcinoma are 65. 3%, 52. 0%, 70. 4% and 69. 4%. The positive rate of p53, p21, PCNA and COX-2 in their resection margin tissues are 23. 5%, 39. 8%, 32. 7% and 30. 6%. So there is no relation between the expression of p53, p21, PCNA and COX-2 in tumor tissue and tumorous grading and TNM staging. (2)There appeared 17 cases of local recurrence in two years, with a recurrence rate of 17. 3%. The recurrence rate of patients with a positive expression of p53, p21, PCNA and COX-2 in resection margin tissue is higher than those with a negative expression(P<0. 05). Among positive cases, the recurrence rate of patients with double positive results is obviously higher than those with single positive results(P< 0. 05). (3)The expression of p21 in p53 positive resection margin tissue is greatly higher than that in negative tissue. The expression of PCNA in p53 positive resection margin tissue is greatly higher than that in negative tissue (P<0. 01); however, the PCNA positive expression in p53 positive cut edge organization rather than in the expression of negative cut edge groups(P>0. 05). CONCLUSION: Through the discussion on the effect of p53, p21, PC- NA and COX-2 in the process of laryngeal carcinoma cell proliferation and local recurrence, the study proposes that biochemical metabolism and molecular structure level abnormal expression occur before the change of cell morphology apparent, and suggests that positive index should be examined regularly and effective foreseeability intervention can be applied to patients with positive expression. PMID- 27382673 TI - [The treatment of otosclerosis using laser assisted stapedotomy with mini incision in external auditory meatus]. AB - OBJECTIVE: To investigate the feasibility of the treatment of otosclerosis using laser stapedotomy with mini incision in the external auditory meatus. METHOD: Thirteen patients(15 ears) with otosclerosis evidence on clinic history. They were all operated using the laser assisted stapedotomy by mini incision in external auditory meatus because of the wide straight canal. Laser resection the tendo musculistapedius and anterior and postrior arch, breaking the articulatioincudostapedia, removing the stapes superstructure, making a hole of 6mm diameter in the rear of stapes footplate by laser drilling, implanting the corresponding length Piston artificial ossicle. RESULT: All the surgeries were successful and the operation time was about one hour. There was only one patient manifested vertigo and nausea after the operation. But the symptoms improved three days later after the expectant treatment. All the incisions were healed in the externals. There was significant difference between the preoperative and postoperative PTA. The air conduct improved in every frequent and the bone conduct improved in 1 kHz, 2 kHz and 4 kHz. CONCLUSION: Laser assisted stapedotomy by mini incision in the external auditory meatus in patients having wide straight canal with otosclerosis can shorten the operation time, minimize the tissue damage, fasten the healing of the incision and reduce the complications postoperatively. In addition, the mini incision is beauty and easy to nurse. PMID- 27382674 TI - [Efficacy of the dust mites drops sublingual immunotherapy in pediatric allergic rhinitis]. AB - OBJECTIVE: To observe the role of the dust mites drops sublingual immunotherapy(SLIT) in pediatric allergic rhiriitis caused by dust mites and compare its efficacy between monosensitized and polysensitized children. METHOD: A total of 77 pediatric allergic rhinitis patients received Dermatophagoides farina extracts sublingual immunotherapy for 2 years were enrolled as desensitization group and were allocated into monosensitized group (41 cases) and polysensitized group (36 cases) according to the number of coexisting allergens. Meanwhile another 33 allergic rhinitis children treated by pharmacotherapy during the period were collected as control group. The total symptom scores (TNSS), total medication scores (TMS) and visual analogue scale(VAS) were assessed at the beginning, six months, 1 year and 2 years of the treatment. SPSS 13. 0 software was used to analyze the data. RESULT: the score of TNSS and VAS in desensitization was slightly higher than the control after six months treatment, but without difference at l year and 2 years; the score of TMS had significantly improved in desensitization compared with the corresponding points in control. All the parameters in monosensitized group were equivalent with polysensitizend group, except the score of TMS was slightly lower than the polysensitizend group at six months. CONCLUSION: Dust mite drops sublingual immunotherapy is effective for the allergic rhinitis children caused by mites. And it has similar immunotherapy efficacy between monosensitized and polysensitized children. PMID- 27382675 TI - [HRCT and MRI image of bilateral large vestibular aqueduct syndrome]. AB - OBJECTIVE: To explore. HRCT and MRI three-dimensional fast imaging employing steady state ac-quisition(3D-FIESTA) imaging features and clinical characteristics of bilateral large vestibular aqueduct syndrome(LVAS). METHOD: The imaging and clinical features of 14 cases of bilateral LVAS identified over a 5-year periodwere retrospectively analyzed. All patients underwent HRCT and MRI 3D-FIESTA scanning of head and neck;MRI three dimensional reconstructions of internal acoustical meatus were also completed at the same time. RESULT: Audiogram showed mild to moderate hearing loss and was progressive. The cut-off values for the coronal midpointand operculum planes on the HRCT scan to diagnose an EVA were 1. 5 mm and 4. 3 mm respectively; the averagevalue was 2. 4 mm. VA expansion degree were not linked to the degree of hearing loss. MRI showed VA andlymph sac abnormalities. Concomitant image finding was cochlear hypoplasia. CONCLUSION: HRCT and MRI 3D-FI-ESTA are important examinations for accurate diagnosis of LVAS. HRCT can acquire the specific size of reamedVA. MRI and 3D reconstructions of internal acoustical meatus can noninasive show more intuitive display ofLVAS and other inner ear malformations than HRCT. PMID- 27382676 TI - [Rare earth elements contents and distribution characteristics in nasopharyngeal carcinoma tissue]. AB - OBJECTIVE: To investigate the rare earth elements(REEs) contents and distribution characteristics in nasopharyngeal carcinoma( NPC) tissue in Gannan region. METHOD: Thirty patients of NPC in Gannan region were included in this study. The REEs contents were measured by tandem mass spectrometer inductively coupled plasma(ICP-MS/MS) in 30 patients, and the REEs contents and distribution were analyzed. RESULT: The average standard deviation value of REEs in lung cancer and normal lung tissues was the minimum mostly. Light REEs content was higher than the medium REEs, and medium REEs content was higher than the heavy REEs content. REEs contents changes in nasopharyngeal carcinoma were variable obviously, the absolute value of Nd, Ce, Pr, Gd and other light rare earth elements were variable widely. The degree of changes on Yb, Tb, Ho and other heavy rare earth elements were variable widely, and there was presence of Eu, Ce negative anomaly(deltaEu=0. 385 5, deltaCe= 0. 523 4). CONCLUSION: The distribution characteristic of REEs contents in NPC patients is consistent with the parity distribution. With increasing atomic sequence, the content is decline wavy. Their distribution patterns were a lack of heavy REEs and enrichment of light REEs, and there was Eu , Ce negative anomaly. PMID- 27382677 TI - [The observation of normal uncinate process mucosa compared with inferior turbinate in epithelium ultrastructure]. AB - OBJECTIVE: To observe the morphological differences between normal uncinate process(UP) mucosa and inferior turbinate mucosa, and explore the physiology function of the UP with the electron microscope. METHOD: The experiment chose 12 patients who have taken nasal endoscopic surgeries(8 cases for normal UP, 4 cases for normal inferior turbinate mucosa). During the surgery, take the mucosa upwards on the filter paper and immediately use scanning electron microscopy and transmission electron microscopy specimens for standard sample preparation methods. Observe the cilia shape, structure and the distribution and the swing direction. RESULT: (1)The internal side and the external side of UP mucosa and inferior turbinate mucosa are all pseudostratified ciliated columnar epithelium, the shapes of cilia are classic "9+2" structures. The distribution of cilia on internal and external lateral of UP and inferior turbinate mucosa are in high density. (2)The direction of cilia on normal inferior turbinate mucosa are generally swing to up and backwards; the cilia on internal lateral of the UP generally swing towards inner side, down and backwards; the cilia on external lateral of the UP generally swing towards down and backwards. CONCLUSION: The cilia on internal side and the external side of UP mucosa and inferior turbinate mucosa are in the same structure and shape, but the swing direction of cilia have their own characteristics. It can be concluded that the internal and external lateral of UP may have different functions in nasal sinuses mucus cilia clearance system. PMID- 27382678 TI - [CO2 laser assisted posterior cordotomy for bilateral vocal cord paralysis]. AB - OBJECTIVE: To investigate the feasibility and efficacy of CO2 laser assisted posterior cordotomy for patients with bilateral paralysis of the vocal cord. METHOD: Twenty-one patients with bilateral paralysis of the vocal cord underwent CO2 laser assisted posterior cordotomy in our hospital from Jul. 2009 to Jun. 2015. The causes of the bilateral paralysis of the vocal cord were thyroidectomy in 15 cases, cervical trauma in 2 cases, resection of pituitary tumor in 1 case, inflammation in 1 case and without cause in 2 cases. Ten patients underwent tracheotomy before the operation; 9 patients underwent tracheotomy after the operation; 2 cases without tracheotomy. RESULT: The tracheotomy tube was plugged next day after posterior cordotomy. Lots of patients were breathing well without any effort. A few patients were breathing hard, so the tracheotomy tube was plugged discontinuously. Seventeen patients were decannulated 1 year after operation. Two patients were failed to decannulated. The patients were followed up for 3 months 6 years after operation, and all of them were breathing well. CONCLUSION: Our limited experience showed that CO2 laser assisted posterior cordotomyis an effective and reliable surgical procedure for patients with bilateral paralysis of the vocal cord. PMID- 27382679 TI - [Diagnosis and treatment of bilateral bronchial foreign body in children]. AB - OBJECTIVE: To discuss the clinical characteristics of bilateral bronchial foreign body in children, increase the curative rate and reduce the complications. METHOD: The clinical data of 35 cases with bilateral bronchial foreign body in children were retrospectively analysed, including surgery, key surgery points, and postoperative combined therapy. RESULT: The foreign bodies of all cases were removed under intravenous general and tropical anesthesia without complications. CONCLUSION: The bilateral bronchial foreign body is a serious case, the timely and effective treatment can lower the mortality rate and postoperative complications. The children lack of oxygen for a long time before and in operation should be give comprehensive therapy, for example: sedation and hyperbaric oxygen. PMID- 27382680 TI - [A study on vowel duration and word length of adductor spasmodic dysphonia]. AB - OBJECTIVE: To understand the vowel duration and statement reading of the adductor spasmodic dysphonia (ADSD) patients compared with their normal controls, and provide ideas for clinical diagnosis and treatment. METHOD: Twenty-nine ADSD patients were included in the research, with 31 normal controls. All subjects filled in form voice handicap index (VHI) by themselves. Maximum phonetic time (MPT) and maximum loudness phonetic time(MLPT) were tested on /a/ sound for all patients. Also, all the patients were required to read aloud a standard mandarin assay named , duration were measured with Praat5. 0 software after sounds were collected. A one-way t-test was performed to compare spasmodic group with control group on VHI, MPT, MLPT and duration for reading standard sentences. Pearson/Spearman correlation was tested. Result: The VHI of the 29 ADSD patients is 89+/-12, and their normal controls 15+/-16, indicating that the VHI in ADSD group is significantly higher than in the control group(P<0. 01). The MPT of the ADSD group is(16. 9+/-9. 8 s), and the control group is (25. 3+/-10.0)s, indicating that MPT in the ADSD group is significantly shorter than the control group(P<0. 01). The MLPT of the ADSD group is (15.7+/-7. 6)s, and the control group is (26. 5+/-11. 4)s, indicating that MLPT in the ADSD group is significantly shorter than the control group (P<0. 01). The duration of standard sentence reading of the ADSD group is (55.0+/-14. 2)s, and the control group is (37. 8+/-4. 8)s, indicating that the duration of standard sentence reading in the ADSD group is significantly longer than the control group (P<0. 01). Correlation analysis showed that MPT and MLPT are related within the ADSD group(r=0. 697,P< 0.01), other indexes being tested have no significant correlations. CONCLUSION: The voice disorder condition of the ADSD patients is significantly worse than normal people. Their pronunciations on continuous vowels are not lasting compared with normal people. In the meantime, their ability to read sentences is worse than normal people, needing longer time to complete the reading task. There is a significant correlation between MLPT and MPT, which can be used as an alternative to MPT. PMID- 27382681 TI - [Application of continuous sutures for nasal septum after septoplasty]. AB - OBJECTIVE: To investigate the efficacy and safety of nasal septal suture in septoplasty. METHOD: Sixty patients who had undergone septoplasty were allocated into two groups: packing group and suturing group. Post-operative signs and symptoms (visual analogue scale) were compared between the two groups. RESULT: The patients of packing group experienced significantly more postoperative pain, epiphora, tinnitus, ear fullness, sleep disturbance and nasal congestion(P<0. 05). No statistically significant difference between two groups in hemorrhage (P>0. 05). CONCLUSION: Nasal septum continuous suture is a feasible method to replace nasal packing after septoplasty. PMID- 27382682 TI - [Prevalence of bilateral abnormalities of unilateral Meniere disease]. AB - OBJECTIVE: To analyze the abnormal conditions of the affected ear and the contralateral ear of patients with unilateral Meniere's disease and the prevalence of bilateral abnormalities among these unilateral Meniere disease population, providing reference for the clinical treatment strategies for Meniere disease. METHOD: A retrospective analysis of 106 Meni6re disease cases was performed, the abnormal incidence of the affected ears, the contralateral ears and the bilateral abnormalities were calculated, and the disease characteristics were analyzed. RESULT: The bilateral ears abnormal incidence of unilateral Meniere disease was 35. 85% (38/106); the cochlear symptoms of the contralateral ears often occurred 2. 25 years later of the symptoms of Meni6re disease; contralateral cochlear symptoms included at least two symptoms of tinnitus, deafness and ear fullness; 39. 47%(15/38) patients with bilateral abnormalities would appear binaural hearing impairment. CONCLUSION: This study showed that about one-third of unilateral Meniere diseases have binaural symptoms, among which about one-third would occur bilateral hearing loss. Therefore, it is necessary to consider the course of disease and the symptoms of the contralateral ear before taking damage or destructive method for treating Meniere's disease clinically. PMID- 27382683 TI - [The assessment of sequential treatment for subjective and objective benign paroxysmal positional vertigo]. AB - OBJECTIVE: To compare the effectiveness of sequential treatment for subjective and objective benign paroxysmal positional vertigo(BPPV). METHOD: The efficacy of sequential treatment for nineteen vertical semicircular canal S-BPPV patients(Group A) and forty-five vertical semicircular canal O-BPPV patients(Group B) who were admitted to our hospital between January 2014 and July 2015 was retrospectively analyzed and compared, treatment of five cases with horizontal semicircular canal S-BPPV was reported here as well. RESULT: The number of repositioning maneuver for Group A was 2 - 6 times (average: 4. 21+/-1. 18) while 2 - 3 times (average: 2. 29 +/- 0. 46) for Group B. There was significant difference between the two groups(P<0. 01). The effective rate of initial treatment for Group A was 78. 9%(15/19) while 82. 2%(37/45)for Group B. After one weeks treatment, the effective rate for Group A changed to be 89. 5% (17/19)while 88. 9% (40/45) for Group B. Non-significant difference was found in the two groups neither in the initial nor one weeks treatment. On three months' follow-up, one in Group A and two in Group B relapsed, and they were cured after treated in the initial treatment. The recurrence for Group A was 5. 3%(1/19) while 4. 4%(2/45) for Group B and there was non-significant difference. The five cases with horizontal semicircular canal S-BPPV were completely free of disease after undergoing treatment. CONCLUSION: The sequential treatment is effective for both vertical semicircular canal S-BPPV and vertical semicircular canal O-BPPV, but the former needs more repositioning maneuver times. The repositioning maneuver, combined with drug therapy and head-shake-in-supine-position method is recommended for horizontal semicircular canal S-BPPV. PMID- 27382684 TI - [The results and drug susceptibility of respiratory secretion culture of children with trachea bronchial foreign bodies]. AB - OBJECTIVE: To analyze the distribution and drug resistance of the pathogenic bacteria in respiratory secretion in children with trachea bronchial foreign bodies so as to assist physicians in clinical prescription. METHOD: Sputum specimens of 622 children with trachea bronchial foreign bodies were collected,and the drug susceptibility test was peformed. RESULT: Pathogenic bacteria were detected in 124(19. 94%) of 622 sputum specimens. Most detected gram-negtive bacilli were highly sensitive to amikacin, ciprofloxacin, ceftriaxone, cefepime and ceftazidime, no strains were resistant to imipenem and meropenem; 42 strains were gram-positive bacilli. The former were highly sensitive to levofloxacin and chloramphenico,the latter were highly sensitive to ciprofloxacin, moxifloxacin and linezolid, no strains were resistant to rifampicin and vancomycin. CONCLUSION: The frequent pathogenic bacteria in respiratory secretion in children with trachea bronchial foreign bodies include gram-negtive bacilli such as enterobacter cloacae, klebsiella pneumonia, escherichia coli, acinetobacter baumannii, serratia marcescens, and gram-positive bacilli such as streptococcus pneumonia,staphylococcus aureus. The detected gram negtive bacilli were sensitive to imipenem and meropenem;the detected gram positive bacilli were sensitive to rifampicin and vancomycin. PMID- 27382685 TI - [Clinical efficacy and quality of life evaluation of BPPV by different reduction methods]. AB - OBJECTIVE: Comparative analysis of the clinical curative effect of manipulative reduction and TRV- CRP treatment of BPPV, comfort degree during reset and quality of life improvement. METHOD: One hundred and thirty-two patients with BPPV were randomly divided into two groups ,one group underwent the traditional manip- ulative reduction, the other group with TRV-CRP. DRI and VAS was evaluated in the pre and after treatment and evaluation of the efficacy was conducted. The results of two groups were compared. RESULT: The effective rate of manipulative reduction after a week treatment was 89. 23% and TRV-CRP.was 98. 51%, which was higher in TRV-CRP group than that of the manipulation reduction group(P<0. 05). The comfort degree of the manipulation reduction group was 4. 54+/-2. 48,higher than the TRV CRP group which was 5. 48+/-1. 44 (P<0. 05). The score of DHI showed no significant difference before treatment between manipulation reduction group and TRV-CRP group(P>0. 05), the score of the two groups were decreased after a week of reduction, but the improvement of TRV-CRP group was higher than that of manipulation reduction group(P<0. 05). CONCLUSION: The success rate of TRV-CRP was higher than that of manipulative reduction,but manipulative reduction comfort degree was higher than TRV-CRP, the two methods can both improve the quality of life of patients with BPPV. TRV-CRP has many advantages over manipulative reduction, but manipulative reduction is simple with low cost, and the effect is still a great advantage. In clinical work, we should reasonable combine the two methods,so as to improve the cure rate of RPPV. PMID- 27382686 TI - [Effects of different surgical procedures on immunity of children with obstructive sleep apnea hypopnea syndrome]. AB - OBJECTIVE: To explore the effects of pure adenoidectomy,adenoidectomy with partial tonsillectomy,and adenoidectomy with total tonsillectomy on humoral and cellular immunity of children with OSAHS. METHOD: The children with OSAHS diagnosed by polysomnography were divided into pure adenoidectomy group(group A),adenoidectomy with partial tonsillectomy group(group B), and adenoidectomy with total tonsillectomy(group C), and there were 50 cases in each group. The serum IgG, IgA, IgM level and peripheral blood T cell subgroup per-centage were detected at 6 months preoperatively and postoperatively. Tonsil grading and polysomnography wereconducted, recording symptoms improvement situation at postoperative 6 months. RESULT: There was no statisticallysignificant difference compared with preoperative(P>0. 05) in humoral immunity and cellular immunity index ofpostoperative 6 months. There was no significani difference(P>C. 05) in curative effect among three groups in the 6th month post-operatively. CONCLUSION: All of these three surgical procedures had no obvious effect on humoral orcellular immune function in children, and could effectively treat children OSAHS. PMID- 27382687 TI - [Clinical characteristics of 100 vestibular migraine cases]. AB - OBJECTIVE: To analyze the characteristics of vestibular migraine (VM), in order to understand the auditory and vestibular function. METHOD: One hundred cases of confirmed or suspected VM patients were observed. Routine examination including pure tone test, vestibular dual temperature test and vestibular evoked myogenic potential(VEMP) and video head impulse test(v-HIT) Were conducted. RESULT: The incidence of male and female was about 1.00 : 2. 57. The average age of onset was 47 years, of which the youngest was 19 years old, and the oldest was 74 years old. Ninty-three cases of patients presented with vestibular sensitive performance, including photophobia, phonophobia,or motion sensitive. Fourty-two patients had migraine at the onset of the disease. Thirty-four patients had cochiear symptoms, including tinnitus, ear fullness, or epicophosis. In seventeen cases of fatigue, tension or poor sleep can cause vertigo. Nine patients had low blood pressure, 7 patients presented with hypertension. Two cases of vertigo were closely related to the change of position, and 1 case had visual aura. In the experiment, 94 patients had undergone VEMP test,with 44 cases of abnormal VEMP value. Seventy-nine patients had been examined v-HIT,of whom 2 patients were abnormal (both of which were reduced). Pure tone audiometry was abnormal in 35 cases. Five cases of patients showed abnormal vestibular-double temperature test. CONCLUSION: Vestibular migraine is more prone to female, with young middle age, and can be accompanied by cochlear symptoms. Vestibular function tests (low frequency and high frequency) are normal. PMID- 27382688 TI - [Individualized surgical planning of benign tumor in external auditory canal under microscope]. PMID- 27382689 TI - [The combined treatment of auricular keloid with multi-function electric ion surgery]. PMID- 27382690 TI - [Surgical treatment of auricular pseudocyst]. PMID- 27382691 TI - [Children severe OSAHS with pectus excavatum: a case report]. AB - The primary etiopathology of pediatric OSAHS includes tonsil or adenoid hypertrophy. Severe OSAHS contributes to or aggravates thoracic deformity, which is rarely reported. In the current report, This children sleep snoring more than 4 years, increasing with thoracic severe depression during sleep 2 days. Clinical examination indicated tonsil and adenoid hypertrophy, and polysomnography revealed OSAHS . The symptoms of OSAHS and severe inhalation-related sternum depression disappeared rapidly after tonsillectomy. Our findings indicated that OSAHS were the major causes underlying funnel chest in children. The rarity of the incidence may result in missed diagnosis or misdiagnosis. Polysomnography was recommended for the child diagnosed with funnel chest accompanied by upper airway stenosis. PMID- 27382692 TI - [Rare giant retroauricular epidermoid cyst: a case report]. AB - Epidermnoid cysts are henign, cutaneous cysts which commonly occur on face, neck and trunk. Retroauricular epidermoid cyst is rare reported which should be differentiated from auricle pseudocyst, lipoma, steatocystoma and fibroma. The hitopathological examination is a gold standard of diagnosis. Surgery of complete excision is the first choice of treatment methods. PMID- 27382693 TI - [The treatment of subglottic pleomorphic adenoma using the hypothermia plasma ablation: two cases report]. AB - Subglottic pleomorphic adenoma is a rare disease . Surgery is the main curative treatment. To review some clinical cases and to summarize the characteristics and treatment experience of this disease,it is expected that we can provide more clinical thought and therapeutic strategy for subglottic pleomorphic adenoma. PMID- 27382694 TI - [Endoscopic removal of a dental foreign body from maxillary sinus via anterior prelacrimal recess approach: a case report]. AB - We present a rare case of dental foreign body from maxillary sinus in a 21-year woman who was hospitalized because of oral cavity and nasal sinus leak for 3 months when doing cheek-bulging action. Admission diagnosis :dental maxillary sinus"foreign body" (left); chronic maxillary sinusitis (left). Computed tomographic scan showed irregular high density shadow in the left maxillary sinus. The "foreign body" was removed via anteri- or prelacrimal recess approach, which was supposed to be the iatrogenic foreign body - alveolar bone. PMID- 27382695 TI - [Postoperative reconstruction of facial squamous cell carcinoma by cervicothoracic flap and temporal flap: a case report]. AB - To report one case of postoperative reconstruction of facial squamous cell carcinoma by cervicotho-racic flap and temporal flap in our hospital. Clinical symptoms of the patient are facial mass and tumor ulceration.The patient had chronic bronchitis. On admission, the right side of the patient face was found to have a mass of about 6. 5 cm X 5. 0 cm, and the middle is about 2. 5 cm X 2. 5 cm X 1. 0cm ulcer, the neck has no swollen lymphnodes by palpation. After imaging and pathological examination,the patient was diagnosed as right facial squamouscell carcinoma and chronic bronchitis. PMID- 27382696 TI - [Stent implantation in the treatment of pharynx anastomotic stenosis after cervical esophageal resection: a case report]. AB - We report the treatment of one patient with pharynx anastomotic stenosis after cervical esophagealresection by stent implantation. The patient suffered from serious pharynx anastomotic stenosis after gastric-pha-ryngeal anastomosis. After balloon-dilatation,a domestic self-expanding Z-stents was implanted in the stricture ofthe esophagus under the X-rays. After stent implantation, the patient has been leading a normal life for threeyears. Balloon dilatation and stent implantation is an effective and safe method in the treatment of patients withpharynx anastomotic stenosis. PMID- 27382697 TI - [Immune function alteration in children after tonsillectomy and(or) adenoidectomy]. AB - Tonsillectomy and(or) adenoidectomy are effective procedures for children with chronic tonsillitis, diseases associated with the tonsil and other adenotonsillar diseases, and obstructive sleep apnea-hypopnea syndrome. Since the tonsil and adenoid gland play a dual role in fluid and cell immunity, whether adenotonsillectomy results in the abnormal immune function in children after the surgery has always been the focus of attention. This review focuses on the alterations and impacts on immunity in children after tonsillectomy and/or adenoidectomy. Recent studies confirmed that in short term the immune index may be slightly reduced after the tonsil and adenoid resection in children, however, the decline has no clinical significance because the remaining mucosa-associated lymphoid tissue can compensate for removal of the tonsils and adenoids. Over time, the immune index tends to be normal. The children's postoperative short term decline in the immune index will gradually recover to the preoperative level or there is no significant difference compared with that in normal children. Therefore, long-term immune function did not decline after tonsil and adenoid resection in children. PMID- 27382698 TI - [Cause and treatment of unilateral vocal cord paralysis]. AB - Unilateral vocal cord paralysis(UVCP) is defined as affected side vocal cord emerges immobility or motion weakening and abnormal tension due to unilateral intrinsic laryngeal muscles suffering from disorder about motor nerve. The patients usually present with hoarse voice, disability of high pitch, cough, aspiration, or a combination of these symptoms. There are increasing therapeutics researches and case analyses regarding UVCP in recent years. Thus this review summarized the progression about its causes and treatment methods. PMID- 27382699 TI - [Not Available]. PMID- 27382700 TI - [Not Available]. PMID- 27382701 TI - [Not Available]. PMID- 27382702 TI - Rembert Dodoens (1517-1585). Pioneer in Rare Diseases and Orphan Drugs. PMID- 27382703 TI - [Not Available]. PMID- 27382704 TI - [Not Available]. PMID- 27382705 TI - the ACA turns 6 as the election hype continues. PMID- 27382706 TI - therapy services: from ancillary to necessary. AB - Physical and occupational therapy and speech language pathology services are assuming an increasingly important role as healthcare providers transition to value-based care. Finance leaders can support the efforts of therapy leaders by working with them to: Determine priorities regarding level of care. Establish appropriate staffing and productivity metrics. Promote accurate and thorough charge-capture efforts. Broaden the referral base for therapy services PMID- 27382707 TI - rampingup for bundled payments: fostering hospital-physician alignment. AB - When hospitals embark on bundled payment programs, they should take steps to ensure physicians are on board. Key steps include: Contacting physicians while in the planning stages so they can prepare to participate in the new model. Establishing resources and processes designed to make compliance easier. Educating physicians about the importance of coding and documentation. PMID- 27382708 TI - provider venture capital funds: investing in innovation. AB - As health systems continue to embrace disruptive innovation, they are increasingly likely to consider making a move into venture capital. Working in venture capital can benefit a health system in several ways, including: Allowing it to operate outside of bureaucracy and align projects with its core values. Encouraging innovation within the organization. Enabling it to respond quickly to changes in the market. PMID- 27382709 TI - capital planning for a new era. AB - Capital planning has become more centralized at many health systems. Managing the capital budget for IT continues to be a challenge. The arrival of value-based payment is influencing some organizations' strategic capital investments. PMID- 27382710 TI - have you looked at your capital process lately? AB - Hospital executives seeking to instill rigor into their organization's capital review process should focus their attention on four areas: Establishing and ensuring compliance with clear internal policy and procedures governing the organization's capital equipment review and purchase process. Cultivating a collaborative culture, while eschewing an "us against them" mentality. Managing provider-vendor relationships. Having a clear definition of success for the capital review process that is championed by executive leadership. PMID- 27382711 TI - making technology talk: how interoperability can improve care, drive effidcincy, and reduce waste. AB - Health systems and providers that search out more interoperable technology can help move the industry toward greater productivity using a multistep approach. Assemble a team of champions to address the interoperability issue. Describe the desired state of interoperability for the organization. Assess the current state of interoperability in the organization. Identify the gaps between the current state and the desired state. Develop a road map for addressing the gaps. Achieve an immediate win by selecting a quickly attainable goal. Maintain focus and communicate successes. PMID- 27382713 TI - minding the gap: getting on board with collaboration-driven revenue models. PMID- 27382712 TI - new lease accounting and health care. AB - Recently released lease accounting standards from the Financial Accounting Standards Board (FASB) present three significant challenges for healthcare organizations: All leases must be reported on a company's balance sheet, increasing liabilities on the balance sheets of healthcare organizations considerably. Contractual agreements not previously considered leases will now be treated as leases. Classification of some equipment leases could change. PMID- 27382714 TI - value and the revenue cycle. PMID- 27382715 TI - [Annual review of capillary electrophoresis technology in 2015]. AB - This paper reviews the capillary electrophoresis (CE) in 2015. The literatures searched from ISI Web of Science ranged in 2015. 1. 1-2015. 12. 31 are classified and introduced based on CE-MS method, methodology research, detection and enrichment, chiral separation and basic applications of CE. Six international and two national conferences are included and the important reports are introduced briefly. In the end, the standards of CE method for the analyses of monoclonal antibodies, water, wines and food approved in China and some other countries are listed. PMID- 27382716 TI - Research development of designing flow cells for optical absorption detectors. AB - The optical absorption detector is one of the most commonly used detectors for high performance liquid chromatography (HPLC). As a core part of this kind of detector, the designs of flow cells, where light passes through samples for acquiring samples information, will affect the performance of a detector. In order to enhance the signal to noise ratio of detectors and reduce the bands broadening that come from flow cells, it is necessary to design a flow cell with a longer optical path length and a less cell volume while maintaining the luminous flux. However the limitations of the machining capacity make it difficult to increase the optical path length, reduce the cell volume and keep or increase the luminous flux simultaneously. It is a challenge to optimize the designing and machining of flow cells so as to improve the performance of detectors. This review discusses the development of designing flow cells based on the detection principle in some aspects of increasing the optical path length, reducing the cell volume, taking the advantages of total reflection and so on. At the same time, some of the designs are illustrated in detail. These various ideas and structures are significant references for designing flow cells and developing optical absorption detectors. PMID- 27382717 TI - [Microdevice for the investigation of high-glucose induced lifespan and the protective effect of polydatin in C. elegans]. AB - Caenorhabditis elegans (C. elegans) has been widely used as a model organism for biomedical research due to its sufficient homology with human at molecular or genomic level. In this work, we describe a microfluidic device not only to investigate the response of C. elegans including lifespan and oxidative stress, but also to evaluate the protective effect of polydatin induced by high-glucose condition. It was found that the mean lifespan of worms was significantly reduced and the oxidative stress protein GST-4 was increased in worms that are subjected to high glucose. However, a certain dose of polydatin could weaken the increased oxidative stress induced by high-glucose and extend the lifespan, indicating the protective effect of polydatin against the toxic of high-glucose. The established approach is simple to operate, easy for realtime imaging and multiparatemer evaluations in parallel, providing a potential platform for drug evaluation/screening in a high throughput format at single animal resolution. PMID- 27382718 TI - [Effects of carrier liquid and flow rate on the separation in gravitational field flow fractionation]. AB - Gravitational field-flow fractionation is the simplest field-flow fractionation technique in terms of principle and operation. The earth' s gravity is its external field. Different sized particles are injected into a thin channel and carried by carrier fluid. The different velocities of the carrier liquid in different places results in a size-based separation. A gravitational field-flow fractionation (GrFFF) instrument was designed and constructed. Two kinds of polystyrene (PS) particles with different sizes (20 um and 6 um) were chosen as model particles. In this work, the separation of the sample was achieved by changing the concentration of NaN3, the percentage of mixed surfactant in the carrier liquid and the flow rate of carrier liquid. Six levels were set for each factor. The effects of these three factors on the retention ratio (R) and plate height (H) of the PS particles were investigated. It was found that R increased and H decreased with increasing particle size. On the other hand, the R and H increased with increasing flow rate. The R and H also increased with increasing NaN3 concentration. The reason was that the electrostatic repulsive force between the particles and the glass channel wall increased. The force allowed the samples approach closer to the channel wall. The results showed that the resolution and retention time can be improved by adjusting the experimental conditions. These results can provide important values to the further applications of GrFFF technique. PMID- 27382719 TI - [Preparation and chromatographic performance of a silica-bonded (4 cyclopentadienyl benzoic acid-iron-toluene) hexafluorophosphoric acid stationary phase]. AB - Based on the unique molecular structure of ferrocene and its potential as a new liquid chromatography separation medium, a new silica-bonded (4-cyclopentadienyl benzoic acid-iron-toluene) hexafluorophosphoric acid stationary phase was prepared. The structure of this new material was characterized by infrared spectroscopy, elemental analysis, thermogravimetric analysis et al. The chromatographic performance and retention mechanism of this new stationary phase were evaluated using different solute probes, including polycyclic aromatic hydrocarbons (PAHs), positional isomers of naphthylamine, positional isomers of nitro-aniline, nitroimidazoles, organic phosphorus et al. It could provide various action sites for different solutes in normal-phase chromatography such as pi electron transfer, pi-pi electron interactions, dipole-dipole interactions, and electrostatic interactions with the substrates. And the possible separation mechanisms are discussed. PMID- 27382720 TI - [Determination of 250 pesticide residues in vegetables using QuEChERS-ultra performance liquid chromatography-tandem mass spectrometry]. AB - A multiresidue analytical method for the determination of 250 pesticide residues in vegetables was developed by using QuEChERS-ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The target compounds were extracted with acetonitrile containing 1% (v/v) acetic acid, purified by a mixed sorbent of MgSO4, primary secondary amine (PSA), graphitized carbon black (GCB) and C18, separated on a Waters ACQUITYTM UPLC BEH C18 column (100 mm x 2. 1 mm, 1.7 um) and detected by UPLC-MS/MS. Anhydrous magnesium sulfate was used as a dewatering agent. The effects of the amounts of MgSO4, PSA, GCB and C18 added on the recoveries of 250 pesticides were investigated. The results showed that the purification effect was best when 300 mg MgSO4, 200 mg PSA, 10 mg GCB and 100 mg C18 in 2 mL of the extract were added. For the 250 pesticide residues, the limits of detection (LODs) of the method were from 0. 01 to 50. 00 g/kg. The recoveries obtained ranged from 60. 1% to 120% at three spiked levels in Chinese chives with the relative standard deviations between 3. 5% and 19. 5% using matrix matched external standard method. The results showed that the method is able to meet requirements of the multiresidue detection of the 250 pesticides in vegetable. The method has the advantages of rapidity, simplicity, high sensitivity and better purification effect. It is suitable for the rapid determination of the common pesticides in vegetables, and it provides a strong guarantee for the risk assessments of the quality and safety of vegetables. PMID- 27382721 TI - [Dynamic behavior of aldicarb and its metabolites in cabbage by liquid chromatography-tandem mass spectrometry]. AB - A liquid chromatography-tandem mass spectrometry ( LC-MS/MS ) method was developed for the study of dynamic behavior of aldicarb and its metabolite residues in cabbage. Aldicarb was applied onto cultivated cabbages. The pesticides concentrations were measured periodically (between application and harvest) , and modeled to illustrate the dynamic behavior. The results showed that the liner ranges of aldicarb and its metabolites were from 0. 005 to 0. 2 mg/L, and the recoveries ranged from 78. 9% to 108. 5% with the relative standard deviations of 2. 03%- 8. 91% (n = 8). The aldicarb in cabbage increased at first with the first-order kinetic equation model of c = 0. 020(0.136t) with the correlation coefficient (r2) of 0. 888, and then decreased with the equation of c = 0. 65e(-059t) with the r2 of 0. 979 and the half-life of 29. 1 d. The reducing processes of aldicarb-sulfone and aldicarb-sulfoxide both matched the first-order kinetic equations (c = 23. 4e(-0.044t) and c = 4. 54e(-0.027t) with r2 of 0. 916 and 0. 972 respectively. To meet the limitation requirement of 0. 01 mg/kg, 70. 7, 226. 6 and 176. 3 d were respectively necessary for aldicarb, aldicarb-sulfone and aldicarb-sulfoxide. Final residues of aldicarb-sulfone and aldicarb-sulfoxide were still more than the limitation requirements, indicating that aldicarb should not be used in vegetables of growth cycle shorter than 120 d. This study provided theoretical basis for dynamic behavior of aldicarb residue and its safe use in vegetables. PMID- 27382722 TI - [Simultaneous determination of the residues of four beta2-agonists in animal foods by modified high performance liquid chromatography-tandem mass spectrometry]. AB - An analytical method was developed to simultaneously determine the residues of four beta2-agonists in animal foods by high performance liquid chromatography/electrospray-tandem mass spectrometry (HPLC-MS/MS). Samples were extracted with 5% (mass fraction) trichloracetic acid, and then cleaned up by two solid phase extraction cartridges (HLB and ProElut PXC). Quantification of the four beta2-agonists was achieved by HPLC-MS/MS in multiple reaction monitoring (MRM) using internal standard method. The limits of detection (S/N=3) of clenbuterol, salbutamol, ractopamine and terbutaline were 0. 05, 0. 05, 0. 05 and 0. 2 ug/kg, and the limits of quantification (S/N= 10) were 0. 25, 0. 25, 0. 1 and 0. 5 ug/kg, respectively. The average recoveries of the four beta2-agonists spiked in blank samples at the spiked levels of 2. 5, 5 and 10 ug/kg were 90. 3% 120. 5% with the relative standard deviation (RSD) range of 1. 60%-9. 33%. The method is reliable, sensitive, good recovery and repeatability. It is suitable for the determination of the residues of the four beta2-agonists in animal foods. PMID- 27382723 TI - [Determination of 23 antibiotics and 3 beta-agonists in livestock drinking water by ultra performance liquid chromatography-tandem mass spectrometry coupled with solid-phase extraction]. AB - A method has been developed for the simultaneous determination of 23 antibiotics (four categories) and 3 beta-agonists in livestock drinking water using solid phase extraction and ultra performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI MS/MS). The samples were adjusted pH to 5. 0, added Na2EDTA, enriched and cleaned-up by an HLB solid phase extraction cartridge. The target compounds were confirmed and quantified by UPLC-ESI MS/MS with external standard method for the anti- biotics and internal standard method for the beta-agonists. The recoveries were assessed by using lab tap water as matrix. The average recoveries of the 23 antibiotics and the 3 beta agonists were in the range of 50. 7%-104. 6% and the relative standard deviations (RSDs) were 2. 6%-8. 8% (n= 3). Under the optimal conditions, the calibration curves of the 23 antibiotics and the 3 beta-agonists showed good linearity with the correlation coefficients better than 0. 994. The limits of detection (LODs, S/N>=3) ranged from 0. 01-0. 20 ng/L. The developed method was applied to analyze the livestock drinking waters in 36 Beijing intensive livestock farms. The results showed that some antibiotics were detected. PMID- 27382724 TI - [Determination of ginkgolic acids in the ginkgo biloba extract and its preparations by ultra high performance liquid chromatography-triple quadrupole mass spectrometry]. AB - An analytical method was developed for the determination of ginkgolic acids in ginkgo biloba extract and its preparations by ultra high performance liquid chromatography-triple quadrupole mass spectrometry. A chromatographic column, Agilent Poroshell 120 EC-C18 (50 mm x 3. 0 mm, 2.7 um), was used with methanol-l% acetic acid (90 :10, v/v) as the mobile phase. The ginkgo acids were detected by electrospray ionization mass spectrometry in negative mode with multiple reaction monitoring (MRM) mode. Ginkgo acids C13:0, C15:1 and C17:1 possessed good linear correlations in the mass concentration range from 2 to 200 ug/L, with the correlation coefficients more than 0. 999. The mean recoveries at the spiked levels of 5, 20 and 100 ug/L were in the range of 86. 3%-114. 3%, and the RSDs were 0. 5%-13. 6%. The limits of detection and quantification were 0. 003-0. 08 ug/g and 0. 01-0. 19 ug/g, respectively. The method was successfully applied to the analysis of actual samples. PMID- 27382725 TI - [Determination of succinic acid in desvenlafaxine succinate by high performance ion-exclusion chromatography and high performance ion-exchange chromatography]. AB - New methods were developed for the determination of succinic acid in desvenlafaxine succinate (DVS) by high performance ion-exclusion chromatography (HPIEC) and high performance ion-exchange chromatography (HPIC). HPIEC and HPIC methods were used separately to determinate the succinic acid in DVS. With HPIEC, the sample was diluted with 2. 50 x 10(-3) mol/L sulfuric acid solution and filtrated by 0. 22 um polyether sulfone filter membrane, and then analyzed by HPIEC directly without any further pretreatment. The analytical column was Phenomenex Rezex ROA-organic Acid H+(8%) (300 mmx7. 8 mm). The mobile phase was 2. 50x10(-3) mol/L sulfuric acid solution at the flow rate of 0. 5 mL/min. The column temperature was set at 40 degrees C, and the detection wavelength was 210 nm. The injection volume was 10 KL. The assay was quantified by external standard method. With HPIC, the sample was diluted with ultrapure water and filtrated by 0. 22 um polyether sulfone filter membrane, and then analyzed by HPIC directly without any further pretreatment. The analytical column was Dionex IonPac AS11-HC (250 mm x 4 mm) with a guard column IonPacAG11-HC (50 mm x 4 mm). Isocratic KOH elute generator was used at the flow rate of 1. 0 mL/min. The detection was performed by a Dionex suppressed (DIONEX AERS 500 4-mm) conductivity detector. The injection volume was 10 uL. The content computation was performed with peak area external reference method. The results of HPIEC method for succinic acid were 28. 8%, 28. 9% and 28. 9%, while the results of HPIEC method were 28. 2%, 28. 6% and 28. 6%. The results of HPIEC and HPIC methods were not significantly different. The two methods can both be used to determine the contents of succinic acid in DVS. The surveillance analytical method should be chosen according to the situation. PMID- 27382726 TI - [Determination of 21 organophosphorus pesticides in tea by gas chromatography mass spectrometry coupled with hydroxylated multi-walled carbon nanotubes based on dispersive solid-phase extraction]. AB - A rapid determination method of 21 organophosphorus pesticides in tea was developed by QuEChERS method using modified multi-walled carbon nanotubes (MWCNTs OH), primary-secondary amine (PSA) and MgSO4 coupled with gas chromatography-mass spectrometry. The pesticide residues in tea were extracted with a hexane-acetone (2:1, v/v) mixture, and cleaned up by dispersive solid-phase extraction using MWCNTs-OH and primary-secondary amine (PSA) as the sorbents. After centrifugation and filtration, the target compounds were analyzed by gas chromatography-mass spectrometry and quantified by the external standard method. Under the optimized conditions, good linearities were obtained in the range of 0. 01- 0. 50 mg/kg. The average recoveries were in the range of 81. 5% -109. 4% at three spiked levels, with relative standard deviations (RSDs, n = 5 ) of 2. 3% - 10. 6%. The limits of quantification were 0. 001-0. 040 mg/kg. This method is simple, fast, sensitive, cheap, and can meet the requirements of the rapid detection of organophosphorus pesticides in tea. PMID- 27382727 TI - [Determination of short-chain chlorinated paraffins in ambient air using high volume sampling combined with high resolutimi gas chromatography-electron capture negative ion-low resolution mass spectrometry]. AB - An analytical method for quantifying short-chain chlorinated paraffins (SCCPs) in ambient air using high-volume sampling combined with high resolution gas chromatography-electron capture negative ion-low resolution mass spectrometry ( HRGC-ECNI-LRMS) was developed. An acidified silica gel column and a basic alumina column were used to optimize the cleanup procedures. The results showed a good linearity (R2>0. 99) between the total response factors and the degree of chlorination of SCCPs in the content range of 58. 1%-63. 3%. The limits of detection (S/N >=3) and the limits of quantification (S/N >= 10) were 4. 2 and 12 ug, respectively. The method detection limit (MDL) for SCCPs was 0. 34 ng/m3 (n = 7). The recoveries of SCCPs in air samples were in the range of 81. 9% to 94. 2%. It is demonstrated that the method is suitable for the quantitative analysis of SCCPs in air samples. PMID- 27382728 TI - [Determination of volatile organic compounds in ambient air by thermal desorption gas chromatography-triple quadrupole tandem mass spectrometry]. AB - A method was established for the simultaneous determination of 23 volatile organic compounds (VOCs) in ambient air with combination of thermal desorption (TD) and gas chromatography-triple quadrupole tandem mass spectrometry (GC MS/MS). The air samples were collected by active sampling method using Tenax-TA sorbent tubes, and desorbed by thermal desorption. The analytes were determined by GC-MS/MS in selected reaction monitoring (SRM) mode, and internal standard method was applied to quantify the VOCs. The results of all the 23 VOCs showed good linearities in low level (0. 01-1 ng) and high level (1-100 ng) with all the correlation coefficients (r2) more than 0. 99. The method quantification limits were between 0. 000 08-1 ug/m3. The method was validated by means of recovery experiments (n = 6) at three spiked levels of 2, 10 and 50 ng. The recoveries between 77% and 124% were generally obtained. The relative standard deviations (RSDs) in all cases were lower than 20%, except for chlorobenzene at the low spiked level. The developed method was applied to determine VOCs in ambient air collected at three sites in Shanghai. Several compounds, like benzene, toluene, ethylbenzene, m-xylenes, p-xylenes, styrene, 1, 2, 4-trimethylbenzene and hexachlorobutadiene were detected and confirmed in all the samples analyzed. The method is highly accurate, reliable and sensitive for monitoring the VOCs in ambient air. PMID- 27382729 TI - [Identification of isoparaffin components in petroleum middle fractions]. AB - The identification of isoparaffin components in petroleum middle fractions including kerosene and diesel fuels was investigated by gas chromatography-mass spectrometry (GC/MS). The isodewaxing middle fraction and distilled diesel were selected as the objective samples for identification. It was shown that the isoparaffin components in middle fraction were well separated with their branched alkyl substituent numbers on a capillary chromatographic column in selected ion monitoring (SIM) mode of GC/MS. The identification for C10-C24 isoparaffins was realized with the technique of GC/MS, such as the fragmentation pathways of electron ionization and SIM technique, boiling point rule, published retention indices and theoretical rules about component retention behavior in GC including carbon number rule etc. Finally, the retention indices for the mono-substituted, di-substituted and multi-substituted isoparaffins from C10 to C24 were presented, which could provide an overall knowledge of isoparaffin distribution at carbon number level in fuels. Meanwhile, the peaks that could be well resolved in each isoparaffin group were also identified, and the detailed data for about 80 C10 C21 methyl-substituted isoparaffins and isoprenoid biomarkers were also given. The results showed that in isodewaxing middle fraction studied, the mono substituted and di-substituted isoparaffins were the main paraffins, whereas in distilled diesel studies, the mono-substituted isoparaffins and isoprenoid biomarkers were the main ones. PMID- 27382730 TI - [Wearable Healthcare Technology: Opportunities and Challenges for Biomedical Engineering]. PMID- 27382731 TI - [A Maternal Health Care System Based on Mobile Health Care]. AB - Wearable devices are used in the new design of the maternal health care system to detect electrocardiogram and oxygen saturation signal while smart terminals are used to achieve assessments and input maternal clinical information. All the results combined with biochemical analysis from hospital are uploaded to cloud server by mobile Internet. Machine learning algorithms are used for data mining of all information of subjects. This system can achieve the assessment and care of maternal physical health as well as mental health. Moreover, the system can send the results and health guidance to smart terminals. PMID- 27382732 TI - [Low-power Wireless Micro Ambulatory Electrocardiogram Node]. AB - Ambulatory electrocardiogram (ECG) monitoring can effectively reduce the risk and death rate of patients with cardiovascular diseases (CVDs). The Body Sensor Network (BSN) based ECG monitoring is a new and efficien method to protect the CVDs patients. To meet the challenges of miniaturization, low power and high signal quality of the node, we proposed a novel 50 mmX 50 mmX 10 mm, 30 g wireless ECG node, which includes the single-chip an alog front-end AD8232, ultra low power microprocessor MSP430F1611 and Bluetooth module HM-11. The ECG signal quality is guaranteed by the on-line digital filtering. The difference threshold algorithm results in accuracy of R-wave detection and heart rate. Experiments were carried out to test the node and the results showed that the pro posed node reached the design target, and it has great potential in application of wireless ECG monitoring. PMID- 27382733 TI - [Design of a Front-end Device of Heart Rate Variability Analysis System Based on Photoplethysmography]. AB - Heart rate variability (HRV) is the difference between the successive changes in the heartbeat cycle, and it is produced in the autonomic nervous system modulation of the sinus node of the heart. The HRV is a valuable indicator in predicting the sudden cardiac death and arrhythmic events. Traditional analysis of HRV is based on a multielectrocardiogram (ECG), but the ECG signal acquisition is complex, so we have designed an HRV analysis system based on photoplethysmography (PPG). PPG signal is collected by a microcontroller from human's finger, and it is sent to the terminal via USB-Serial module. The terminal software not only collects the data and plot waveforms, but also stores the data for future HRV analysis. The system is small in size, low in power consumption, and easy for operation. It is suitable for daily care no matter whether it is used at home or in a hospital. PMID- 27382734 TI - [Intraocular Pressure Sensor Based on a Contact Lens]. AB - Intraocular pressure detection has a great significance for understanding the status of eye health, prevention and treatment of diseases such as glaucoma. Traditional intraocular pressure detection needs to be held in the hospital. It is not only time-consuming to doctors and patients, but also difficult to achieve 24 hour-continuous detection. Microminiaturization of the intraocular pressure sensor and wearing it as a contact lens, which is convenient, comfortable and noninvasive, can solve this problem because the soft contact lens with an embedded micro fabricated strain gauge allows the measurement of changes in corneal curvature to correlate to variations of intraocular pressure. We fabricated a strain gauge using micro-electron mechanical systems, and integrated with the contact lens made of polydimethylsiloxane (PDMS) using injection molding. The experimental results showed that the sensitivity was 100. 7 uV/um. When attached to the corneal surface, the average sensitivity of sensor response of intraocular pressure can be 125.8 uV/mm Hg under the ideal condition. PMID- 27382735 TI - [Study on an Exoskeleton Hand Function Training Device]. AB - Based on the structure and motion bionic principle of the normal adult fingers, biological characteristics of human hands were analyzed, and a wearable exoskeleton hand function training device for the rehabilitation of stroke patients or patients with hand trauma was designed. This device includes the exoskeleton mechanical structure and the electromyography (EMG) control system. With adjustable mechanism, the device was capable to fit different finger lengths, and by capturing the EMG of the users' contralateral limb, the motion state of the exoskeleton hand was controlled. Then driven by the device, the user's fingers conducting adduction/abduction rehabilitation training was carried out. Finally, the mechanical properties and training effect of the exoskeleton hand were verified through mechanism simulation and the experiments on the experimental prototype of the wearable exoskeleton hand function training device. PMID- 27382736 TI - [Portable Epileptic Seizure Monitoring Intelligent System Based on Android System]. AB - The clinical electroencephalogram (EEG) monitoring systems based on personal computer system can not meet the requirements of portability and home usage. The epilepsy patients have to be monitored in hospital for an extended period of time, which imposes a heavy burden on hospitals. In the present study, we designed a portable 16-lead networked monitoring system based on the Android smart phone. The system uses some technologies including the active electrode, the WiFi wireless transmission, the multi-scale permutation entropy (MPE) algorithm, the back-propagation (BP) neural network algorithm, etc. Moreover, the software of Android mobile application can realize the processing and analysis of EEG data, the display of EEG waveform and the alarm of epileptic seizure. The system has been tested on the mobile phones with Android 2. 3 operating system or higher version and the results showed that this software ran accurately and steadily in the detection of epileptic seizure. In conclusion, this paper provides a portable and reliable solution for epileptic seizure monitoring in clinical and home applications. PMID- 27382737 TI - [An Electroencephalogram-driven Personalized Affective Music Player System: Algorithms and Preliminary Implementation]. AB - In order to monitor the emotional state changes of audience on real-time and to adjust the music playlist, we proposed an algorithm framework of an electroencephalogram (EEG) driven personalized affective music recommendation system based on the portable dry electrode shown in this paper. We also further finished a preliminary implementation on the Android platform. We used a two dimensional emotional model of arousal and valence as the reference, and mapped the EEG data and the corresponding seed songs to the emotional coordinate quadrant in order to establish the matching relationship. Then, Mel frequency cepstrum coefficients were applied to evaluate the similarity between the seed songs and the songs in music library. In the end, during the music playing state, we used the EEG data to identify the audience's emotional state, and played and adjusted the corresponding song playlist based on the established matching relationship. PMID- 27382738 TI - [Classification and Correlative Technology Development of Wearable Devices]. AB - Wearable devices bring us an innovative human-computer interaction which plays an irreplaceable role in enhancing the users' ability in environmental awareness, acquirements of their own state and "ubiquitous" computing power. Since 2013, wearable devices have quickly appeared around us. In this article we classify most of the wearable devices which have been appeared in the markets or reported in the literature according to their functions and the positions where they are worn. Furthermore, we review the technologies related to wearable devices, such as sensing technology, wireless communication, power manager, display technology and big data. At last, we analyze the challenges which the wearable devices will face in near future, and look forward to development trends of wearable devices. PMID- 27382739 TI - [Influence of Medication on the Oscillatory and Dynamic Characteristics of Subthalamic Local Field Potentials in Patients with Parkinson's Disease]. AB - The dysfunction of subthalamic nucleus is the main cause of Parkinson's disease. Local field potentials in human subthalamic nucleus contain rich physiological information. The present study aimed to quantify the oscillatory and dynamic characteristics of local field potentials of subthalamic nucleus, and their modulation by the medication therapy for Parkinson's disease. The subthalamic nucleus local field potentials were recorded from patients with Parkinson's disease at the states of on and off medication. The oscillatory features were characterised with the power spectral analysis. Furthermore, the dynamic features were characterised with time-frequency analysis and the coefficient of variation measure of the time-variant power at each frequency. There was a dominant peak at low beta-band with medication off. The medication significantly suppressed the low beta component and increased the theta component. The amplitude fluctuation of neural oscillations was measured by the coefficient of variation. The coefficient of variation in 4-7 Hz and 60-66 Hz was increased by medication. These effects proved that medication had significant modulation to subthalamic nucleus neural oscillatory synchronization and dynamic features. The subthalamic nucleus neural activities tend towards stable state under medication. The findings would provide quantitative biomarkers for studying the mechanisms of Parkinson's disease and clinical treatments of medication or deep brain stimulation. PMID- 27382740 TI - [Brain Efficient Connectivity Analysis of Attention Based on the Granger Causality Method]. AB - The study of brain information flow is of great significance to understand brain function in the field of neuroscience. The Granger causality is widely used functional connectivity analysis using multivariate autoregressive model based on the predicted mechanism. High resolution electroencephalogram (EEG) signals of ten healthy subjects were collected with a visual selective attention task. Firstly, independent component analysis was used to extract three spatially independent components of the occipital, parietal, and frontal cortices. Secondly, the Granger causal connectivity was computed between these three regions based on the Granger causality method and then independent sample t-test and bootstrap were used to test the significance of connections. The results showed that Granger causal connectivity existed from frontal to occipital and from parietal to occipital in attentional condition, while causal connectivity from frontal to occipital disappeared in unattentional condition. PMID- 27382741 TI - [Recognition of Low Arousal Level Electroencephalogram in the Vigilance Based on Wavelet Packet Rhythm and Support Vector Machine]. AB - Poor and monotonous work could easily lead to a decrease of arousal level of the monitoring work personnel. In order to improve the performance of monitoring work, low arousal level needs to be recognized and awakened. We proposed a recognition method of low arousal by the electroencephalogram (EEG) as the object of study to recognize the low arousal level in the vigilance. We used wavelet packet transform to decompose the EEG signal so the EEG rhythms of each component were obtained, and then we calculated the parameters of relative energy and energy ratio of high-low frequency, and constructed the feature vector to monitor low arousal state in the operation. We finally used support vector machine (SVM) to recognize the low arousal state in the simulate operation. The experimental results showed that the method introduced in this article could well distinguish low arousal level from arousal level in the vigilance and it could also get a high recognition rate. Have been compared with other analysis methods, the present method could more effectively recognize low arousal level and provide better technical support for wake-up mechanism of low arousal state. PMID- 27382742 TI - [Estimation of the Power Spectrum of Heart Rate Variability Using Improved Welch Method to Analyze the Degree of Fatigue]. AB - Heart rate variability (HRV) is an important point to judge a person's state in modern medicine. This paper is aimed to research a person's fatigue level connected with vagal nerve based on the HRV using the improved Welch method. The process of this method is that it firstly uses a time window function on the signal to be processed, then sets the length of time according to the requirement, and finally makes frequency domain analysis. Compared with classical periodogram method, the variance and consistency of the present method have been improved. We can set time span freely using this method (at present, the time of international standard to measure HRV is 5 minutes). This paper analyses the HRV's characteristics of fatigue crowd based on the database provided by Physio Net. We therefore draw the conclusion that the accuracy of Welch analyzing HRV combining with appropriate window function has been improved enormously, and when the person changes to fatigue, the vagal activity is diminished and sympathetic activity is raised. PMID- 27382743 TI - [MicroRNA Target Prediction Based on Support Vector Machine Ensemble Classification Algorithm of Under-sampling Technique]. AB - Considering the low accuracy of prediction in the positive samples and poor overall classification effects caused by unbalanced sample data of MicroRNA (miRNA) target, we proposes a support vector machine (SVM)-integration of under sampling and weight (IUSM) algorithm in this paper, an under-sampling based on the ensemble learning algorithm. The algorithm adopts SVM as learning algorithm and AdaBoost as integration framework, and embeds clustering-based under-sampling into the iterative process, aiming at reducing the degree of unbalanced distribution of positive and negative samples. Meanwhile, in the process of adaptive weight adjustment of the samples, the SVM-IUSM algorithm eliminates the abnormal ones in negative samples with robust sample weights smoothing mechanism so as to avoid over-learning. Finally, the prediction of miRNA target integrated classifier is achieved with the combination of multiple weak classifiers through the voting mechanism. The experiment revealed that the SVM-IUSW, compared with other algorithms on unbalanced dataset collection, could not only improve the accuracy of positive targets and the overall effect of classification, but also enhance the generalization ability of miRNA target classifier. PMID- 27382744 TI - [Analysis of Influence on Single Eythrocyte Injury Caused by Oscillating Boundary Flow Field]. AB - The implantable axial blood pump, driven by external electromagnet, is studied recently. It oscillats when it is running because of the elastic implanted environment and driving force disequilibrium, etc. In this paper, a model of single erythrocyte in vibrated flow field was built to simulate the deformation and force of the erythrocyte. By using the mechanical injury principle of blood in blood pump, we studied the injury of a single erythrocyte resulted from oscillating boundary flow field. The research results indicated that the shape of the erythrocyte, force and velocity field nearby, which are affected by oscillating boundary flow field, all cause injury to the erythrocyte. All the researches shown in the present paper are expected to provide theoretical foundation for lightening hemolysis by the blood pump. PMID- 27382745 TI - [Fast Implementation Method of Protein Spots Detection Based on CUDA]. AB - In order to improve the efficiency of protein spots detection, a fast detection method based on CUDA was proposed. Firstly, the parallel algorithms of the three most time-consuming parts in the protein spots detection algorithm: image preprocessing, coarse protein point detection and overlapping point segmentation were studied. Then, according to single instruction multiple threads executive model of CUDA to adopted data space strategy of separating two-dimensional (2D) images into blocks, various optimizing measures such as shared memory and 2D texture memory are adopted in this study. The results show that the operative efficiency of this method is obviously improved compared to CPU calculation. As the image size increased, this method makes more improvement in efficiency, such as for the image with the size of 2,048 x 2,048, the method of CPU needs 52,641 ms, but the GPU needs only 4,384 ms. PMID- 27382746 TI - [Design of High Frequency Signal Detecting Circuit of Human Body Impedance Used for Ultrashort Wave Diathermy Apparatus]. AB - The present circuit was designed to apply to human tissue impedance tuning and matching device in ultra-short wave treatment equipment. In order to judge if the optimum status of circuit parameter between energy emitter circuit and accepter circuit is in well syntony, we designed a high frequency envelope detect circuit to coordinate with automatic adjust device of accepter circuit, which would achieve the function of human tissue impedance matching and tuning. Using the sampling coil to receive the signal of amplitude-modulated wave, we compared the voltage signal of envelope detect circuit with electric current of energy emitter circuit. The result of experimental study was that the signal, which was transformed by the envelope detect circuit, was stable and could be recognized by low speed Analog to Digital Converter (ADC) and was proportional to the electric current signal of energy emitter circuit. It could be concluded that the voltage, transformed by envelope detect circuit can mirror the real circuit state of syntony and realize the function of human tissue impedance collecting. PMID- 27382747 TI - [Design of Electrocardiogram Signal Generator Based on Typical Electrocardiogram Database]. AB - Using LabVIEW programming and high-speed multifunction data acquisition card PCI 6251, we designed an electrocardiogram (ECG) signal generator based on Chinese typical ECG database. When the ECG signals are given off by the generator, the generator can also display the ECG information annotations at the same time, including waveform data and diagnostic results. It could be a useful assisting tool of ECG automatic diagnose instruments. PMID- 27382748 TI - [Research and Design of an Experimental Apparatus Based on the "Open Fireplace" in Xuanwei District]. AB - Xuanwei district in Yunnan Province of China has pretty high incidence of lung cancer in China, even a- round the world. Studies have shown that there exists a close relationship between lung cancer and local indoor air pollution caused by Bituminous coal. Considering that the indoor air pollution in Xuanwei District is caused by "open fireplace", an indoor air pollution simulation system was designed, and an F344 rats lung damage model was estab- lished for this indoor air pollution fireplace. The model is based on indoor air pollution simulation system with signal multiplexer control and multi-channel acquisition, and mining PID algorithm was used for polynomial fitting to each test point, and a relatively constant PM2. 5 air pollution status was simulated. The results showed that the system could simulate a variety of states of air pollution, provide a new test method for evaluation of human injury caused by indoor air pollution and a new idea for the study of the incidence of lung cancer in Xuanwei district and other places. PMID- 27382749 TI - [Cytological Study in vitro on Co-delivery of siRNA and Paclitaxel within Solid Lipid Nanoparticles to Overcome Multidrug Resistance in Tumors]. AB - Multidrug resistance (MDR) remains the major obstacle to the success of clinical cancer chemotherapy. P-glycoprotein (P-gp), encoded by the MDR1, is an important part with complex mechanisms associated with the MDR. In order to overcome the MDR of tumors, we in the present experimental design incorporated small interfering RNA (siRNA) targeting MDR1 gene and anticancer drug paclitaxel (PTX) into the solid lipid nanoparticles (SLNs) to achieve the combinational therapeutic effects of genetherapy and chemotherapy. In this study, siRNA-PTX SLNs were successfully prepared. The cytotoxicity of blank SLNs and siRNA-PTX SLNs in MCF-7 cells and MCF-7/ADR cells were detected by MTT; and the uptake efficiency of PTX in MCF-7/ADR cells were detected via HPLC method; quantitative real-time PCR and flow cytometry were performed to investigate the silencing effect of siRNA-PTX- SLNs on MDR1 gene in MCF-7/ADR cells. The results showed that PTX loaded SLNs could significantly inhibit the growth of tumor cells, and more importantly, the MDR tumor cells treated with siRNA-PTX-SLNs showed the lowest viability. HPLC study showed that SLNs could enhance the cellular uptake for PTX. Meanwhile, siRNA delivered by SLNs significantly decreased the P-gp expression in MDR tumor cells, thus increased the cellular accumulation of rhodamine123 as a P-gp substrate. In conclusion, the MDR1 gene could be silenced by siRNA-PTX-SLNs, which could promote the growth inhibition efficiency of PTX on tumor cells, leading to synergetic effect on MDR tumor therapy. PMID- 27382750 TI - [Study of the Effect of Cholecystokinin-Induced Acute Pancreatitis on the Free Running Rhythm of Mouse]. AB - The present paper reports the effect of pancreatitis induced by cholecystokinin (CCK) on free-running rhythm of locomotor activity of the ICR mice, and analyzes the interaction of inflammatory diseases and acute pancreatitis with circadian rhythm system. In the study, the mice were modeled under different phases of acute pancreatitis in DD status (Double Dark, constant dark condition). By comparing of the inflammatory status and the indicators of rhythm before and after modeling of the running wheel activity group and the rest group, it was observed that the rest group showed more possibility of inflammation than the activity group did in ICR mice model of acute pancreatitis. In the rest phase model, the extension of the period is particularly longer. The results presented indicated that CCK-induced acute pancreatitis impacted free activity rhythm of ICR mice. Also in a free running model under different phase, the inflammation severity was proved significantly different. This study provides possible clues for the research of the pathogenesis of acute pancreatitis severe tendency. PMID- 27382751 TI - [Evaluation on Ability to Detect the Intracranial Hematoma with Different Density Using C-Arm Cone-beam Computed Tomography Based on Animal Model]. AB - This study aims to evaluate the ability of C-arm cone-beam CT to detect intracranial hematomas in canine models. Twenty one healthy canines were divided into seven groups and each group had three animals. Autologous blood and contrast agent (3 mL) were slowly injected into the left/right frontal lobes of each animal. Canines in the first group, the control group, were only injected with autologous blood without contrast agent. Each animal in all the 7 groups was scanned with C-arm cone-beam CT and multislice computed tomography (MSCT) after 5 minutes. The attenuation values and their standard deviations of the hematoma and uniformed brain tissues were measured to calculate the image noise, signal to noise ratio (SNR) and contrast to noise ratio (CNR). A scale with scores 1-3 was used to rate the quality of the reconstructed image of different hematoma as a subjective evaluation, and all the experimental data were processed with statistical treatment. The results revealed that when the density of hematoma was less than 65 HU, hematomata were not very clear on C-arm CT images, and when the density of hematoma was more than 65 HU, hematomata showed clearly on both C-arm CT and MSCT images and the scores of them were close. The coherence between the two physicians was very reliable. The same results were obtained with C-arm cone beam CT and MSCT grades in measuring SD value, SNR, and CNR. The reasonable choice of density detection range of intracranial hematoma with C-arm cone-beam CT could be effectively applied to monitoring the intracranial hemorrhage during interventional diagnosis and treatment. PMID- 27382752 TI - [Research on Cardiac Structure and Function in the Overweight and Obese population and Influence Factors]. AB - In this study we performed Tissue Doppler Imaging (TDI), two-dimensional speckle tracking imaging (2D- STI) and three-dimensional speckle tracking imaging (3D STI) on enrolled healthy, overweight and obese groups (34 subjects in each group), respectively, to analyze cardiac structure and its function. Compared with healthy group, global longitudinal strain (GLS), global circumferential strain (GCS), global area strain(GAS) and global radial strain (GRS) decreased progressively (P < 0.05). The ratio of early diastolic mitral inflow velocity to global early diastolic strain rate of left ventricle (E/e'sr) (r = 0.466, P < 0.001), GLS (r = 0.502, P < 0. 001), GCS (r = 0.426, P < 0.001), GAS (r = 0.535, P < 0.001) and GRS (r = -0.554, P < 0.001) were correlated with body mass index (BMI). E/e'sr (r = 0.37, P = 0.003), GLS (r = 0.455, P < 0.001), GCS (r = 0.282, P = 0.02), GAS (r = 0.412, P < 0.001) and GRS (r = -0.471, P < 0.001) were correlated with free fatty acid (FFA). Stepwise multiple linear regression revealed that BMI was independently correlated with E/e'sr, GLS, GCS, GAS and GRS. Waist to hip ratio (WHR) was independently correlated with GLS, GCS, GAS and GRS. FFA was independently correlated with E/e'sr (P < 0.05). The study showed that cardiac structure changed and impaired left ventricular global systolic and diastolic function in overweight and obes population. Moreover, BMI, WHR and FFA may be independent influence factors of cardiac function in overweight and obese population. PMID- 27382753 TI - [Effect of Stellate Ganglion Block on Bilateral Regional Cerebral Oxygen Saturation and Postoperative Cognitive Function]. AB - The present study was to examine the effect of stellate ganglion block (SGB) on bilateral regional cerebral oxygen saturation (rSO2) and postoperative cognitive function. Eighty patients undergoing selective coronary artery bypass graft with cardiopulmonary bypass (CPB) were randomly and equally divided into two groups. The patients in group S were given right SGB with ropivacaine, while the patients in group C were injected with normal saline. We compared the bilateral rSO2 after SGB. Minimum Mental State Examination (MMSE), Visual Verbal Learning Test (VVLT), and Digital Span Test (DST) were applied to observe the effect on cognitive function. We found that the incidence of postoperative cognitive dysfunction (POCD) 7 days after surgery in group S was lower than that in group C. The level of blocked side rSO2 of S group were significantly higher before CPB time of rewarming than that before SGB (P < 0.05), much higher than corresponding non blocked side rSO2 before CPB (P < 0.05), and much higher than rSO2 level in group C before CPB and after CPB (P < 0.05). The non-blocked side rSO2 in group S before anesthesia were much lower than basic levels and those in group C (P < 0.05). It could be concluded from the above results that there was significant increase in the blocked-side rSO2 compared to the non-blocked side and there was significant decrease in the incidence of POCD compared to the control group after SGB. PMID- 27382754 TI - [Preparation of Biological Functional Magnetic Nanoparticles and Study on the Effect of Guiding Endothelial Progenitor Cells In Vitro]. AB - Coprecipitation method was used to prepare triiron tetroxide magnetic nanoparticles enclosed in L-DOPA, and then EDC was used to activate the carboxyl group of L-DOPA after the nanoparticles were synthesized. The carboxyl group of L DOPA formed amide bond with specific amino on the aptamer by dehydration condensation reaction. The surfaces of magnetic nanoparticles were modified with aptamer and L-DOPA. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), nanoparticle size analysis (SEM), magnetic measurement (VSM) and other testing methods were used to detect the magnetic nanoparticles in different stages. The endothelial progeni-tor cells (EPCs) were cocultured with the surface modified magnetic nanoparticles to evaluate cell compatibility and the combination effect of nanoparticles on EPCs in a short period of time. Directional guide of the surface-modified magnetic nanoparticles to endothelial progenitor cells (EPCs) was evaluated under an applied magnetic field and simulated dynamic blood flow condition. The results showed that the prepared magnetic nanoparticles had good magnetic response, good cell compatibility within a certain range of the nanoparticle concentrations. The surface modified nanoparticles could combine with EPCs effectively in a short time, and those nanoparticles combined EPCs can be directionally guided on to a stent surface under the magnetic field in the dynamic flow environment. PMID- 27382755 TI - [Primary Study on Noninvasive Detection of Vascular Function Based on Finger Temperature Change]. AB - By studying the relationship between fingertip temperature changes and arterial function during vascular reactivity test, we established a new non-invasive method for detecting vascular function, in order to provide an assistance for early diagnosis and prevention of cardiovascular diseases. We customized three modules respectively for blood occlusion, measurement of finger temperature and blood oxygen acquisition, and then we established the hardware of data acquisition system. And the software was programmed with Labview. Healthy subjects [group A, n = 24, (44.6 +/- 9.0) years] and subjects with cardiovascular diseases [group B, n = 33, (57.2 +/- 9.9) years)] were chosen for the study. Subject's finger temperature, blood oxygen and occlusion pressure of block side during and after unilateral arm brachial artery occlusion were recorded, as well as some other regular physiological indexes. By time-domain analysis, we extracted 12 parameters from fingertip temperature signal, including the initial temperature (Ti), temperature rebound (TR), the time of the temperature recovering to initial status (RIt) and other parameters from the finger temperature signal. We in the experiment also measured other regular physiological body mass index (BMI), systolic blood pressure (SBP), diastiolic blood pressure (DBP) and so on. Results showed that 8 parameters difference between the two group of data were significant. based on the statistical results. A discriminant function of vascular function status was established afterwards. We found in the study that the changes of finger temperature during unilateral arms brachial artery occlusion and open were closely related to vascular function. We hope that the method presented in this article could lay a foundation of early detection of vascular function. PMID- 27382756 TI - [Design and In Vitro Experimental Study of an Endoscopic Multiple-clip Applier]. AB - Considering the problems such as reposition limited, easily detached and singly fired of the existing clip products, we developed an endoscopic multiple-clip applier which can apply 4 clips fired successively at a time. Th instrument also equipped with an independent grasper which can be used to clamp target tissues. In order to explor its feasibility and effectiveness of endoluminal closure of gastric perforation, 22 pig stomachs were making a 1 cm full-thickness incision from outside and closed by multiple-clip applier (n = 12) in vitro. Outcome was measured by bursting pressure and compared with negative control (n = 5) and hand suture (n = 5). We set a threshold pressure value (10 mm Hg) for a secure closure. Except 2 cases of invalid data, the mean bursting pressures of negative control, multiple-clip applier, hand suture were (1.5 +/- 0.3) mm Hg, (46.0 +/- 7.1) mm Hg, and (72.5 +/- 7.7) mm Hg, respectively. The results showed that bursting pressure of multiple-clip applier was significantly higher than that of negative control (P < 0.05) and threshold value. Multiple-clip applier can be served as an effective and safe device to perform the endoluminal closure of gastric perforation. PMID- 27382757 TI - [Quaternion-based Characterization of Protein alpha Helix]. AB - This paper proposes a method based on quaternion for characterization a helix of proteins. The method defines the parameter called Quaternion Helix Axis Spherical Distance (QHASD) on the basis of mapping protein Calpha frames' helical axis onto a unit sphere, and uses QHASD to characterize the a helix of the protein secondary structure. Application of this method has been verified based on the PDBselect database, with an a helix characterization accuracy of 91.7%. This method possesses significant advantages of high detection accuracy, low computation and clear geometric significance. PMID- 27382758 TI - [Study of Event-related Brain Potential in Children with Attention Deficit Hyperactivity Disorder]. AB - This study aims to explore the differences of event-related potential (ERP) between attention deficit hyperactivity disorder (ADHD) and normal children, so that these differences provide scientific basis for the diagnosis of ADHD. Eight children were identified to be ADHD group by the diagnostic criteria of DSM-IV (diagnostic and statistical manual of mental disorders-IV), and the control group also consisted of 8 normal children. Modified visual-continuous performance test (CPT) was used as the experiment paradigm. The experiment included two major conditions, i. e. Go and NoGo. All the 16 subjects participated in the study. A high density EEG acquisition instrument was used to record the EEG signal and processed these EEG data by means of ERP and spectrum analysis. P2-N2 peak-peak value and spectral peak around 11 Hz were analyzed between ADHD subjects and those in the control group, and then statistical tests were applied to these two groups. Results showed that: (1) Under the condition of Go, ADHD group had a significant lower P2-N2 peak-peak value than the values in the control group (P < 0.05); but under the condition of NoGo there was no significant difference in between. (2) Compared with the control group, the ADHD group had significant lower spectral amplitude around 11 Hz under the condition of NoGo (P < 0.05). However, under the condition of Go the difference was insignificant. In conclusion, there is certain cognitive dysfunction in ADHD children. P2-N2 peak peak value and spectral peak around 11 Hz could be considered as clinical evaluation indexes of ADHD children's cognitive function. These two objective indexes provide an early diagnosis and effective treatment of ADHD. PMID- 27382759 TI - [Core Issues of Mechanical Perfusion in Preservation and Repairing of Donor Liver after Cardiac Death]. AB - The quality of a donor liver after cardiac death is closely associated with energy metabolism during preservation. Ex vivo mechanical perfusion has broad application prospects because this technique can help energy metabolism and repair ischemia injury of donors' livers. Some core issues are presented in this review in order to provide references for propelling secure application of liver transplantation based on donation after cardiac death. PMID- 27382760 TI - [Recent Advances of Biomechanical Studies on Cervical Fusion and Non-fusion Surgery]. AB - This article reviews the progress of biomechanical studies on anterior cervical fusion and non-fusion surgery in recent years. The similarities and differences between animal and human cervical spines as well as the major three biomechanical test methods are introduced. Major progresses of biomechanical evaluation in anterior cervical fusion and non-fusion devices, hybrid surgery, coupled motion and biomechanical parameters, such as the instant center of rotation, are classified and summarized. Future development of loading method, multilevel hybrid surgery and coupling character are also discussed. PMID- 27382761 TI - [Advances in Research on Reendothelialization after Intervention in Artery]. AB - Coronary heart disease is a kind of heart disease that is caused by atherosclerosis. The lipid deposition in the vessel wall results in occlusion of coronary artery and stenosis, which could induce myocardial ischemia and oxygen deficiency. Intervention therapies like percutaneous coronary intervention (PCI) and coronary stent improve myocardial perfusion using catheter angioplasty to reduce stenosis and occlusion of coronary artery lumen. Accordingly, intervention therapies are widely applied in clinic to treat ischemic cardiovascular disease, arterial intima hyperplasia and other heart diseases, which could save the patients' life rapidly and effectively. However, these interventions also damage the original endothelium, promote acute and subacute thrombosis and intimal hyperplasia, and thus induce in-stent restenosis (ISR) eventually. Studies indicated that the rapid reendothelialization of damaged section determined postoperative effects. In this review, reendothelialization of implants after intervention therapy is discussed, including the resource of cells contributed on injured artery, the influences of implanted stents on hemodynamic, and the effects of damaged degree on reendothelialization. PMID- 27382762 TI - [Development of Terahertz Imaging Technology in the Assessment of Burn Injuries]. AB - Terahertz waves have unique properties and advantages, which makes it gain increasing attention and applications in the biomedical field. Burns is a common clinical trauma. Since the water-sensitive and non-destructive characteristics of terahertz, terahertz imaging techniques can be used to detect burns. So far, terahertz imaging technology in the assessment of burn injuries has been developed from ex vivo to in vivo, and high-resolution images can be obtained through the gauzes and plasters. In this paper, we mainly introduces the application of terahertz imaging technology and development in the assessment of burn injuries. PMID- 27382763 TI - [Research Progress of NOS3 Participation in Regulatory Mechanisms of Cardiovascular Diseases]. AB - Cardiovascular disease has been a major threat to human's health and lives for many years. It is of great importance to explore the mechanisms and develop strategies to prevent the pathogenesis. Generally, cardiovascular disease is associated with endothelial dysfunction, which is closely related to the nitric oxide (NO)-mediated vasodilatation. The release of NO is regulated by NOS3 gene in mammals' vascular system. A great deal of evidences have shown that the polymorphism and epigenetic of NOS3 gene play vital roles in the pathological process of cardiovascular disease. To gain insights into the role of NOS3 in the cardiovascular diseases, we reviewed the molecular mechanisms underlying the development of cardiovascular diseases in this paper, including the uncoupling of NOS3 protein, epigenetic and polymorphism of NOS3 gene. The review can also offer possible strategies to prevent and treat cardiovascular diseases. PMID- 27382764 TI - [Analysis Methods of Short-term Non-linear Heart Rate Variability and Their Application in Clinical Medicine]. AB - The linear analysis for heart rate variability (HRV), including time domain method, frequency domain method and time-frequency analysis, has reached a lot of consensus. The non-linear analysis has also been widely applied in biomedical and clinical researches. However, for non-linear HRV analysis, especially for short term non-linear HRV analysis, controversy still exists, and a unified standard and conclusion has not been formed. This paper reviews and discusses three short term non-linear HRV analysis methods (fractal dimension, entropy and complexity) and their principles, progresses and problems in clinical application in detail, in order to provide a reference for accurate application in clinical medicine. PMID- 27382765 TI - [Recent advances of miRNAs in adipose tissues]. AB - microRNAs (miRNAs), a class of endogenous non-coding RNA about 22 nucleotide long, regulate gene expression at the post-transcription level by inhibiting the translation or inducing the degradation of their target mRNAs in organisms. A lot of studies reveal that miRNAs in adipose tissues are involved in adipocyte differentiation and lipid metabolism and modulated by multiple transcription factors, adipocytokines and environmental factors, which form a complex regulatory network maintaining the homeostasis of adipose tissues. The discovery of circulating miRNAs adds new elements to the regulatory network. To study the metabolic diseases such as obesity, we should keep a new insight into the complex dynamic network. In this review, we summarize the latest studies of miRNAs in adipose tissues, which might provide new strategies for the treatment of obesity and other related diseases. PMID- 27382766 TI - [Hemophilia B replacement therapy drugs]. AB - Hemophilia B is an X chromosome linked hereditary hemorrhagic disease, which is caused by the lose function mutation of factor IX (FIX), and significantly affects the patients' lifespan and life quality. The severity of hemophilia B depends on the FIX level in the plasma. By referring to the relevant literatures, we reviewed and summarized hemophilia B replacement therapies. Specifically, we focus on recombinant factor IX products on the market and those in the pipeline, especially on the long-acting factor IX drugs, to provide the basis for researches of new hemophilia B drugs. PMID- 27382767 TI - [Strategies to choose scaffold materials for tissue engineering]. AB - Current therapies of organ failure or a wide range of tissue defect are often not ideal. Transplantation is the only effective way for long time survival. But it is hard to meet huge patients demands because of donor shortage, immune rejection and other problems. Tissue engineering could be a potential option. Choosing a suitable scaffold material is an essential part of it. According to different sources, tissue engineering scaffold materials could be divided into three types which are natural and its modified materials, artificial and composite ones. The purpose of tissue engineering scaffold is to repair the tissues or organs damage, so could reach the ideal recovery in its function and structure aspect. Therefore, tissue engineering scaffold should even be as close as much to the original tissue or organs in function and structure. We call it "organic scaffold" and this strategy might be the drastic perfect substitute for the tissues or organs in concern. Optimized organization with each kind scaffold materials could make up for biomimetic structure and function of the tissue or organs. Scaffold material surface modification, optimized preparation procedure and cytosine sustained-release microsphere addition should be considered together. This strategy is expected to open new perspectives for tissue engineering. Multidisciplinary approach including material science, molecular biology, and engineering might find the most ideal tissue engineering scaffold. Using the strategy of drawing on each other strength and optimized organization with each kind scaffold material to prepare a multifunctional biomimetic tissue engineering scaffold might be a good method for choosing tissue engineering scaffold materials. Our research group had differentiated bone marrow mesenchymal stem cells into bile canaliculi like cells. We prepared poly(L-lactic acid)/poly(epsilon-caprolactone) biliary stent. The scaffold's internal played a part in the long-term release of cytokines which mixed with sustained-release nano-microsphere containing growth factors. What's more, the stent internal surface coated with glue/collagen matrix mixing layer containing bFGF and EGF so could supplying the early release of the two cytokines. Finally, combining the poly(L-lactic acid)/poly(epsilon-caprolactone) biliary stent with the induced cells was the last step for preparing tissue-engineered bile duct. This literature reviewed a variety of the existing tissue engineering scaffold materials and briefly introduced the impact factors on the characteristics of tissue engineering scaffold materials such as preparation procedure, surface modification of scaffold, and so on. We explored the choosing strategy of desired tissue engineering scaffold materials. PMID- 27382768 TI - [Effect of phenolic ketones on ethanol fermentation and cellular lipid composition of Pichia stipitis]. AB - Lignin degradation products are toxic to microorganisms, which is one of the bottlenecks for fuel ethanol production. We studied the effects of phenolic ketones (4-hydroxyacetophenone, 4-hydroxy-3-methoxy-acetophenone and 4-hydroxy 3,5-dimethoxy-acetophenone) derived from lignin degradation on ethanol fermentation of xylose and cellular lipid composition of Pichia stipitis NLP31. Ethanol and the cellular fatty acid of yeast were analyzed by high performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS). Results indicate that phenolic ketones negatively affected ethanol fermentation of yeast and the lower molecular weight phenolic ketone compound was more toxic. When the concentration of 4-hydroxyacetophenone was 1.5 g/L, at fermentation of 24 h, the xylose utilization ratio, ethanol yield and ethanol concentration decreased by 42.47%, 5.30% and 9.76 g/L, respectively, compared to the control. When phenolic ketones were in the medium, the ratio of unsaturated fatty acids to saturated fatty acids (UFA/SFA) of yeast cells was improved. When 1.5 g/L of three aforementioned phenolic ketones was added to the fermentation medium, the UFA/SFA ratio of yeast cells increased to 3.03, 3.06 and 3.61, respectively, compared to 2.58 of the control, which increased cell membrane fluidity and instability. Therefore, phenolic ketones can reduce the yeast growth, increase the UFA/SFA ratio of yeast and lower ethanol productivity. Effectively reduce or remove the content of lignin degradation products is the key to improve lignocellulose biorefinery. PMID- 27382769 TI - [Protective effect and mechanism of beta-CM7 on renin angiotensin system & diabetic cardiomyopathy]. AB - This article aimed at exploring the effects and protective mechanism of beta-CM7 on renin angiotensin system (RAS) in diabetic rats myocardial tissue. We divided 32 male SD rats into 4 groups: control group, diabetic model control group, insulin (3.7x10(-8) mol/d) treatment group and beta-CM7 (7.5x10(-8) mol/d) treatment group. After 30 days, all rats were decapitated and myocardical tissues were collected immediately. After injection, beta-CM7 could decrease the content of Ang II, increase the content of Angl-7. And beta-CM7 could improve the mRNA of AT1 receptor and Mas receptor. beta-CM7 also could improve the mRNA of ACE and ACE2, enhance the activity of ACE and ACE2. These data confirmed tli beta-CM7 could activate ACE2-Angl-7-Mas axis, negative passage in RAS, to inhibit the expression ACE mnRiJA and protein in rat myocardium, alleviate the myocardial tissue damage induced by Ang II. The effect of beta-CM7 on inhibiting myocardium damage might be related to ACE/ACE2 passageway. PMID- 27382770 TI - [Screening of drug resistent gene by cyclical packaging rescue of hepatocellular carcinoma retroviral cDNA libraries]. AB - Multidrug resistant genes are highly expressed in hepatocellular carcinoma that seriousty affects the effect of chemotherapy. Screening of resistant genes from HCC cells and studying its mechanism of drug resistance will be helpful to improve the effecacy of chemotherapy for hepatocellular carcinoma. Here we described an alternative method called cyclical packaging rescue (CPR). First we constructed a retrovirus cDNA library of hepatoma cells and used it to infect fibroblasts. Then we added drugs to screen survival cells. The survival cells, stably integrated helper-free retroviral libraries, were recovered rapidly after transfection with plasmids expressing retroviral gag-pol and env genes. Through this method, retroviral RNAs were directly repackaged into new infectious virions. Recovered retroviral supernatant was then used to reinfect fresh target cells. When performed in concert with selection using functional assays, cDNAs regulating functional responses could be identified by enrichment through multiple rounds of retroviral library recovery and retransmission. Using CPR, we obtained several cDNAs. After a preliminary detection, we found Ribosomal protein S11 (RPS11), Ribosomal protein L6 (RPL6), Ribosomal protein L11 (RPL11), Ribosomal protein L24 (RPL24) possibly had drug resistant function. PMID- 27382771 TI - [Construction of Fat-1 eukaryotic expression vector of excision markers and the establishment of transgenic sheep cell lines]. AB - In order to establish marker-free transgenic cell lines, we cloned Fat-1 gene, attB and Loxp sequences by PCR. Then we inserted these sequences to pN1-EGFP vector and got pEGFP-N1-Fat-1 expression vector. PhiC31 integrase mRNA which was generated by in vitro transcription and a pEGFP-N1-Fat-1 expression vector co electroporated into sheep fetal fibroblasts, and then we got transgenic cell lines expressing green fluorescence. Prokaryotic expression and purification of Cre recombinant protein was performed. Cre recombinant protein was transducted into stably-transfected cell colonies. We identified cell colonies by sequencing and established marker-free transgenic cell lines and eventually- established marker-free transgenic cell lines which were building more safely basic for producing Fat-1 transgenic animals. PMID- 27382772 TI - [Role of NO signal in ABA-induced phenolic acids accumulation in Salvia miltiorrhiza hairy roots]. AB - To investigate roles of nitric oxide (NO) signal in accumulations of phenolic acids in abscisic.acid (ABA)-induced Salvia miltiorrhiza hairy roots, S. miltiorrhiza hairy roots were treated with different concentrations of sodium nitroprusside (SNP)-an exogenous NO donor, for 6 days, and contents of phenolic acids in the hairy roots are determined. Then with treatment of ABA and NO scavenger (2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylimidazoline-1- oxyl-3-oxide, c-PTIO) or NO synthase inhibitor (NG-nitro-L-arginine methyl ester, L-NAME), contents of phenolic acids and expression levels of three key genes involved in phenolic acids biosynthesis were detected. Phenolic acids production in S. miltiorrhiza hairy roots was most significantly improved by 100 umoL/L SNP. Contents of RA and salvianolic acid B increased by 3 and 4 folds. ABA significantly improved transcript levels of PAL (phenylalanine ammonia lyase), TAT (tyrosine aminotransferase) and RAS (rosmarinic acid synthase), and increased phenolic acids accumulations. However, with treatments of ABA+c-PTIO or ABA+L NAME, accumulations of phenolic acids and expression levels of the three key genes were significantly inhibited. Both NO and ABA can increase accumulations of phenolic acids in S. miltiorrhiza hairy roots. NO signal probably mediates the ABA-induced phenolic acids production. PMID- 27382773 TI - [The modified bacterial two-hybrid system]. AB - Bacterial two-hybrid system is a newly developed method for studying protein protein interactions. However, in our studies of the interaction of regulatory proteins in Streptomyces, it was found that the bacterial two-hybrid system is not sensitive enough by the blue-and-white selection on X-gal plate. To overcome this drawback, the reason of false positive clone was firstly determined, which was the disturbance of other direct or indirect regulation on lacZ promoter. Then the disturbance was diluted by introducing multicopy lacZ promoter, which drive another reporter gene gfp. By such design, the sensitivity of the modified bacterial two-hybrid system was significantly inproved and the two different reporters also help to decrease the rate of the false positive clones. Further the evaluation of the modifiedd bacterial two-hybrid system indicated that the sensitivity was significantly improved. PMID- 27382774 TI - [Identification and characterization of a novel hemocyte specific gene Bm04862 in silkworm, Bombyx mori]. AB - Bm04862 is a novel hemocyte-specific gene, which has been identified and cloned through the microarray data in silkworm, Bombyx mori. Initially, we successfully obtained the full-length cDNA sequence of Bm04862 via the rapid amplification of cDNA ends (RACE). The sequence consists of an open reading frame (ORF) with 819 bp, which could encode 273 amino acid residues. The bioinformatics analysis predicted that Bm04862 was a transmembrane protein. Furthermore, qRT-PCR analysis revealed that the expression of Bm04862 was specifically detected in hemocyte and reached a peak at L4M and PP2 stage. Bm04862 was overexpressed in Sf9 insect cells, and the cellular localization indicated that Bm04862 was specifically located in cytoplasm and nuclei membrane. Interestingly, the expression of Bm04862 increas'd dramatically after challenged with Escherichia coli for 24 hours, which predicted its potential role in the innate immune system. Overall, this study could provide the fundamental knowledge for further research. PMID- 27382775 TI - [Preparation and crystallization of Polygonum cuspidatum benzalacetone synthase]. AB - The chalcone synthase (CHS) superfamily of the type III polyketide synthases (PKSs) generates backbones of a variety of plant secondary metabolites. Benzalacetone synthase (BAS) catalyzes a condensation reaction of decarboxylation between the substrates of 4-coumaric coenzyme A and malonyl coenzyme A to generate benzylidene acetone, whose derivatives are series of compounds with various biological activities. A BAS gene Pcpks2 and a bifunctional CHS/BAS PcPKSI were isolated from medicinal plant P. cuspidatum. Crystallographic and structure-based mutagenesis studies indicate that the functional diversity of the CHS-superfamily enzymes is principally derived from small modifications of the active site architecture. In order to obtain an understanding of the biosynthesis of polyketides in P. cuspidatum, which has been poorly described, as well as of its activation mechanism, PcPKS2 was overexpressed in Escherichia coli as a C terminally poly-His-tagged fusion protein, purified to homogeneity and crystallized, which is helpful for the clarification of the catalytic mechanism of the enzyme and lays the foundation for its genetic engineering manipulation. PMID- 27382776 TI - [Effect of ribosome engineering on butenyl-spinosyns synthesis of Saccharopolyspora pogona]. AB - Through introducing mutations into ribosomes by obtaining spontaneous drug resistance of microorganisms, ribosome engineering technology is an effective approach to develop mutant strains that overproduce secondary metabolites. In this study, ribosome engineering was used to improve the yield of butenyl spinosyns produced by Saccharopolyspora pogona by screening streptomycin resistant mutants. The yields of butenyl-spinosyns were then analyzed and compared with the parent strain. Among the mutants, S13 displayed the greatest increase in the yield of butenyl-spinosyns, which was 1.79 fold higher than that in the parent strain. Further analysis of the metabolite profile of S13 by mass spectrometry lead to the discovery of Spinosyn alpha1, which was absent from the parent strain. DNA sequencing showed that there existed two point mutations in the conserved regions of rpsL gene which encodes ribosomal protein S12 in S13. The mutations occurred a C to A and a C to T transversion mutations occurred at nucleotide pair 314 and 320 respectively, which resulted in the mutations of Proline (105) to Gultamine and Alanine (107) to Valine. It also demonstrated that S13 exhibited genetic stability even after five passages. PMID- 27382777 TI - [Microbial drugs: captured again as S&T spotlight: To the special issue "Innovation & Highly Efficient Production of Microbial Drugs"]. PMID- 27382778 TI - [Guest Editor]. PMID- 27382779 TI - [New natural products from the marine-derived Aspergillus fungi-A review]. AB - Marine-derived fungi were the main source of marine microbial natural products (NPs) due to their complex genetic background, chemodiversity and high yield of NPs. According to our previous survey for marine microbial NPs from 2010 to 2013, Aspergillus fungi have received the most of attention among all the marine derived fungi, which accounted for 31% NPs of the marine fungal origins. This paper reviewed the sources, chemical structures and bioactivites of all the 512 new marine NPs of Aspergillus fungal origins from 1992 to 2014. These marine NPs have diverse chemical structures including polyketides, fatty acids, sterols and terpenoids, alkaloids, peptides, and so on, 36% of which displayed bioactivities such as cytotoxicity, antimicrobial activity, antioxidant and insecticidal activity. Nitrogen compounds are the major secondary metabolites accounting for 52% NPs from the marine-derived Aspergillus fungi. Nitrogen compounds are also the class with the highest ratio of bioactive compounds, 40% of which are bioactive. Plinabulin, a dehydrodiketopiperazine derivative of halimide had been ended its phase II trial and has received its phase III study from the third quarter of 2015 for the treatment of advanced, metastatic non-small cell lung cancer. PMID- 27382780 TI - [Progress in streptothricin antibiotics - A review]. AB - Streptothricins are a group of the earliest discovered antibiotics with broad antimicrobial spectrum, and have been used for crop protection. We reviewed the studies on streptothricin resistance, biosynthesis of the three components (streptolidine, carbamoylated D-glucosamine and poly beta-lysine chain) and chemical synthesis of streptothricins. The important aspects for future streptothricin researches were also discussed. PMID- 27382781 TI - [Recent advances in lanthipeptide biosynthesis - A review]. AB - Lanthipeptides are a growing class of ribosomally synthesized and posttranslationally modified peptide (RiPP) natural products. These compounds are widely distributed among taxonomically distant species, and their structures and biological activities are diverse, providing an important source for drug research and developement. In this review, we summarized the recent advances in the understanding of structure, classification, evolution and substrate controlled biosynthetic mechanism of lanthipeptide, attempting to highlight the intriguing chemistry and enzymology in the biosynthesis of this growing family of natural products. PMID- 27382782 TI - [Biosynthesis and metabolic engineering of dithiolopyrrolone - A review]. AB - Dithiolopyrrolones are a family of antibiotics that possess the unique pyrrolinonodithiole (4H-[1,2] dithiolo [4, 3-b] pyrrol-5-one) skeleton. This family of natural products can be divided into three subfamilies: N-methyl-N- acylpyrrothine, N-acylpyrrothine and thiomarinols. So far, more than 27 members of this group of natural products have been reported including the well-known antibiotics holomycin, thiolutin, aureothricin and recently isolated thiomarinols. Dithiolopyrrolones exhibit relatively broad-spectrum antibiotic activities against many Gram-positive, Gram-negative bacteria and parasites. Some dithiolopyrrolones even have antitumor activities. In recent years, several dithiolopyrrolone biosynthetic gene clusters have been reported and their biosynthetic mechanisms have also been intensively studied. This review will give an overview about the biosynthesis and metabolic engineering of the dithiolopyrrolone natural products, and provides references to guide the creation of hybrid "unnatural" dithiolopyrrolones with better bioactivity and low toxicity by synthetic biology. PMID- 27382783 TI - [Advances in the biosynthesis of spinosad - A review]. AB - Spinosad, extracted from Saccharopolyspora spinosa, one of the most successful commercial bio-insecticides, is derived from a family of macrocyclic lactones. It shows excellent potent insecticidal activities, low residue, and low environmental effect. Here, we reviewed the biosynthetic pathway of spinosad, the chemoenzymatic method of spinosad synthesis, and the strain improvement method and the heterologous expression of spinosad. PMID- 27382784 TI - [Functional characterization of gouC and gouD in gougerotin biosynthesis]. AB - OBJECTIVE: To determine the functions of gouC and gouD in gougerotin biosynthesis, disruption of these two genes was performed. As gougerotin producing strain Streptomyces graminearus lacks efficient genetic manipulation system, the gene cluster for gougerotin biosynthesis was heterologously expressed in Streptomyces coelicolor M1146 to facilitate genetic manipulations of gouC and gouD. METHODS: By using fosmid D6-4H containing the complete gougerotin biosynthetic gene cluster, gouC and gouD were disrupted by PCR-targeting method to generate pGOUe-DeltaC and pGOUe-DeltaD. Both pGOUe-DeltaC and pGOUe-DeltaD were introduced into Streptomyces coelicolor M1146 by intergeneric conjugation, thus gouC and gouD disrpution mutants (Ml146-GOUe-AC and M1146-GOUe-DeltaD) were obtained. The gougerotin production of M1146-GOUe-DeltaC and M1146-GOUe-DeltaD were assayed by HPLC analysis. The intermediates accumulated in these mutants were purified and subjected to MS and NMR analyses for structure determinations. Bioassay of these intermediates against tumor cell line were also carried out. RESULTS: Disruption mutants of gouC and gouD failed to produce gougerotin and the mutants accumulated different gougerotin intermediates, which lost their ability to inhibit cancer cell proliferation. CONCLUSION: gouC and gouD are key structual genes in the biosynthesis of gougerotin peptidyl moieties. This study will pave the way for the elucidation of gougerotin biosynthetic pathway. PMID- 27382785 TI - [Efficient production of polyketide products in Streptomyces hosts - A review]. AB - Polyketides represent an important class of structurally and functionally diverse secondary metabolites with high economic value. Among bacteria, Streptomycetes are the main producers of polyketides. To enhance polyketide production in Streptomyces hosts, rational metabolic engineering approaches have been applied, such as overexpressing rate-limiting enzymes, or transcriptional activator, increasing the supply of precursor, removing feedback inhibition by end products and heterologous expression of polyketide biosynthetic gene clusters. In this review, we discuss examples of successful metabolic engineering strategies used to improve polyketide production in Streptomycetes. Meanwhile, we also address future prospective, emerging synthetic biology strategies to dynamically adjust the metabolic fluxes of pathways related to polyketide synthesis. PMID- 27382786 TI - [Progress in heterologous expression of fungal natural products-A review]. AB - Fungal products are important resources for natural drugs. Availabilities of many fungal genome sequences indicate that fungi have the huge potential to produce secondary metabolites. However, many valuable fungal natural products are hard to obtain under regular lab conditions because fungi are slow to grow, difficult to genetically modify, or have low yield of desired metabolites. Therefore, developing a heterologous expression system has been an efficient approach to discover novel natural product and elucidate the complicated biosynthetic pathways. This review describes several heterologous expression systems that have been successfully used for the expression of fungal biosynthetic gene clusters. Also, we address the application perspective based on the emerging DNA assembly technologies. PMID- 27382787 TI - [Progress in developing and applying Streptomyces chassis - A review]. AB - Natural products and their derivatives play an important role in modern healthcare. Their diversity in bioactivity and chemical structure inspires scientists to discover new drug entities for clinical use. However, chemical synthesis of natural compounds has insurmountable difficulties in technology and cost. Also, many original-producing bacteria have disadvantages of needing harsh cultivation conditions, having low productivity and other shortcomings. In addition, some gene clusters responsible for secondary metabolite biosynthesis are silence in the original strains. Therefore, it is of great significance to exploit strategy for the heterologous expression of natural products guided by synthetic biology. Recently, researchers pay more attention on using actinomycetes that are the main source of many secondary metabolites, such as antibiotics, anticancer agents, and immunosuppressive drugs. Especially, with huge development of genome sequencing, abundant resources of natural product biosynthesis in Streptomyces have been discovered, which highlight the special advantages on developing Streptomyces as the heterologous expression chassis cells. This review begins with the significance of the development of Streptomyces chassis, focusing on the strategies and the status in developing Streptomyces chassis cells, followed by examples to illustrate the practical applications of a variety of Streptomyces chassis. PMID- 27382788 TI - [The strategies and research progresses of rational improvement of the yield of microbial drug- A review]. AB - Microbial drug is a large family of small molecules with unusual structural features and potent bioactivities. The production of microbial drug is crucial for its subsequent development and cost. Traditional breeding strategies for microbial drug production have been demonstrated to be remarkably effective, but they have also indicated the drawback of exceptional randomness and high cost. Synthetic biology has recently promised a revival for the rational enhancement of microbial drugs. In this review, we mainly discuss the recent progress from the aspects of promoter engineering, precursor supply, genome shuffling and etc., to delineate the application of the synthetic biology strategies to enhance the production of the microbial drugs, particularly, produced by actinomycetes. PMID- 27382789 TI - [Advances in the regulation of cephalosporin C biosynthesis - A review]. AB - The beta-lactam antibiotic cephalosporin C is produced industrially by Acremonium chrysogenum. Its derivative 7-aminocephalosporanic acid (7-ACA) is the intermediate of most chemical modification cephalosporins that are the most frequently used antibiotics for the therapy of infectious diseases. Due to its importance, the biosynthetic pathway of cephalosporin C has been elucidated in Acremonium chrysogenum. To improve the yield of cephalosporin C and reduce the cost of production, recent studies have been focused on the sophisticated regulation of cephalosporin C biosynthesis. In this review, recent advances in cephalosporin C biosynthesis and regulation are summarized. PMID- 27382790 TI - [ECF-sigma5 in Sreptomyces avermitilis is involved in regulation of avermectin biosynthesis and stress response]. AB - OBJECTIVE: We investegated the role of extracytoplasmic function (ECF) sigma factor, sigma5, in avermectin biosynthesis, morphological differentiation and stress response in S. avermitilis. METHODS: We constructed sig5 gene deletion, complementation and overexpression strains and determined the role of sigma5 in avermectin production and morphological differentiation by shaking flask fermentation and morphological observation of these strains. We used RT-qPCR, EMSA and ChIP assays to identify the target genes of sigma5. We used stress tests to reveal the stress response that sigma5 may be involved in. RESULTS: Determination of avermectin production and morphological observation in sig5 related strains implied that sigma5 inhibits avermectin production, but has no effect on growth or morphology. Deletion of sig5 increased transcription levels of pathway-specific activator gene aveR and structural gene aveAl, but sigma5 did not bind to the promoter regions of aveR and aveAl. RT-qPCR and ChIP assays showed that sigma5 positively regulates the transcription of itself and adjacent genes by binding to the promoter regions of sig5, SA V612, SA V615 and SA V618. Stress tests suggested that sigma5 is involved in responding to osmotic stress. CONCLUSION: Our findings indicated that sigma5 indirectly inhibits avermectin production by affecting transcription of ave genes. PMID- 27382791 TI - [The analysis of major metabolic pathways in Bacillus thuringiensis under alkaline stress]. AB - OBJECTIVE: The study aimed to determine the appropriate stage for exploring the responseof Bacillus thuringiensis to the alkaline stress, to profile the metabolic pathways under this stress. METHODS: Using semi-quantitative RT-PCR and qRT-PCR, the proper stage was defined by monitoring the transcriptional changes of marker gene pspA, which was known as a responsive gene under the alkaline stress. The total RNA was then extracted to perform the microarray hybridizations for samples under stress and control, respectively. Gene Ontology and pathway enrichments were conducted to analyze the global changes of carbon metabolism, metabolism of fatty acid synthesis and amino acid. RESULTS: For B. thuringiensis in the mid-log growth phase, treatment of 28 mmol/L NaOH for 10 mins is the feasible approach to analyze the response of B. thuringiensis to this stress. More than twenty genes encoding important enzymes in glycolytic pathway were up regulated and majority of genes involved in catalyzing alpha-ketoglutarate into malic acid were also found to up-regulated more than two folds. CONCLUSION: By analyzing the gene expression profile, the major metabolisms of B. thuringiensis were found to be clearly enhanced under alkaline stress. Large quantities of acid including malic acid and lactic acid may contribute a lot to the adaptation of alkaline condition. PMID- 27382792 TI - [Cytochrome P450 enzymes and microbial drug development - A review]. AB - Cytochrome P450 enzymes broadly exist in animals, plants and microorganisms. This superfamily of monooxygenases holds the greatest diversity of substrate structures and catalytic reaction types among all enzymes. P450 enzymes play important roles in natural product biosynthesis. In particular, P450 enzymes are capable of catalyzing the regio- and stereospecific oxidation of non-activated C H bonds in complex organic compounds under mild conditions, which overrides many chemical catalysts. This advantage thus warrants their great potential in microbial drug development. In this review, we introduce a variety of P450 enzymes involved in natural product biosynthesis; provide a brief overview on protein engineering, biotransformation and practical application of P450 enzymes; and discuss the limits, challenges and prospects of industrial application of P450 enzymes. PMID- 27382793 TI - [Production of plant-derived natural products in yeast cells - A review]. AB - Plant-derived natural products (PNPs) have been widely used in pharmaceutical and nutritional fields. So far, the main method to produce PNPs is extracting them from their original plants, however, there remains lots of problems. With the concept of synthetic biology, construction of yeast cell factories for production of PNPs provides an alternative way. In this review, we will focus on PNPs' market and application, research progress for production of artemisinin, research progress for production of terpenes, alkaloids and polyunsaturated fatty acid (PUFAs) and recent technology development to give a brief introduction of construction of yeast cells for production of PNPs. PMID- 27382794 TI - [Progress of cell-free protein synthesis system and its applications in pharmaceutical engineering - A review]. AB - Cell-free protein synthesis (CFPS) systems have been widely used for decades as a rapid and efficient tool in fundamental biology. Without the requirements for cell viability and growth, CFPS systems have distinct advantages over in vivo systems for protein production. Recently, great efforts have been made to further optimize CFPS systems to produce proteins at high yields, reduced cost and increased scale, including simplifying extract preparation procedures, developing new energy regeneration systems to protein synthesis, stabilizing substrate supply and promoting protein folding. Nowadays, CFPS systems are emerging as a powerful platform for industrial and high-throughput production of protein therapeutics, providing an alternative solution to solve problems in biopharmaceutical engineering. Moreover, CFPS systems have been successfully applied to high-throughput drug screening, large-scale protein therapeutics production, custom-made anti-cancer vaccines. These achievements highlight that CFPS systems have great potential for a wide range of applications in biopharmaceutical engineering in the future. PMID- 27382795 TI - [Avermectin, from winning the Nobel Prize to "innovation in China"]. AB - The uprise of the superpower nations is always accompanied by the breakthrough and advances of technologies and innovations in the history. Natural products play very important role in human health, such as anticancer molecular taxol, anti-infection drug artemisinin that save a lot of lives, metabolic disease treatment, nutrition and health care. However, more has never been explored. With the 2015 Nobel Prize in Physiology or Medicine awarded to William C. Campbell, Satoshi Omura, and Youyou Tu for the discovery of avermectins and artemisinin respectively, the second "Golden age" in the development of natural product is dawning. China is a "world factory" and natural drugs-rich country, but how to upgrade and advance the industry and realize the China dream? Avermectins, produced by Streptomyces avermitilis, are pesticide with high efficiency and low levels of side effects. However, the low producer and expensive development pattern of high consumption, high contamination is not sustainable. Solving the problem, increasing the production and utilization of raw material, reducing the energy consumption and cost of production, decreasing environmental pollution are key to transform China into a power house. In this paper, we case-study avermectins to review the industry development driven by fundamental research. Institute of Microbiology, Chinese Academy.of Sciences increased the production of avermectin 1000 folds to 9 g/L, which out licensed to new Veyong biochemical Ltd and avermectin Coalitions. As a result, Merck Sharp and Dohme ceased the manufacture of avermectins. The success also shed lights on the improvement of other natural product drugs in China. PMID- 27382796 TI - [Orthobiologic treatment with platelet-rich plasma: is there sufficient evidence for its recommendation?]. AB - In recent years there has been a boom in the use of platelet-rich plasma (PRP) as an orthobiology (therapy based on cell biological agents) material agent. The presence of growth factors and other bioactive agents stored in alpha platelet granules and whose properties are well determined in cell proliferation, angiogenesis and extracellular matrix formation have involved the PRP containing supraphysiological concentrations of autologous platelets in tissue regeneration processes. The relative ease of preparation of PRP, its generally ambulatory application, the almost complete absence of side effects and the possibility to observe satisfactory results of clinical improvement makes the PRP a promising treatment in regenerative processes. However, there is still a lack of knowledge of the mechanism of action of the PRP, creating skepticism regarding their use and potential efficacy. Caution should be taken until the clinical evidence is stablished. On this subject some questions that should be answered in future research are listed below: What is the optimal preparation of PRP? What is the most effective method for the activation of PRP? Which is better, the use of total PRP or only the platelet growth factors? And finally, what pathological conditions should be chosen for the routine application of PRP? The answers to these questions through well-designed studies and systematic reviews by experts, would lead to the routine use of PRP as the recommended treatment. As final conclusion, the AAOS (The American Academy of Orthopaedic Surgeons) made a consideration that today is still valid: in a Forum in 2011 concluded that "the PRP is an option that has not yet been proven." PMID- 27382797 TI - [High activity antiretroviral therapy change associated to adverse drug reactions in a specialized center in Venezuela]. AB - Adverse drug reactions (ADRs) represent the first cause of change of the first line highly active antiretroviral therapy (HAART) regimen, therefore, they constitute the main limiting factor in the long-term follow up of HIV patients in treatment. A retrospective study was carried out in a specialized center in Lara State, Venezuela, including 99 patients over 18 years of age who had change of first-line HAART regimen due to ADRs, between 2010 and 2013. The aims of this research were to describe the sociodemographic and clinical variables, frequency of ADRs related to change of HAART, duration of the first-line HAART regimen, to determine the drugs associated with ARVs and to identify the risk factors. The ADRs constituted 47.5% of all causes of change of first-line HAART regimen, the median duration was 1.08+/-0.28 years. The most frequent ADRs were anemia (34.3%), hypersensitivity reactions (20.2%) and gastrointestinal intolerance (13.1%). The most frequent ARV regimen type was the protease inhibitors-based regimen (59.6%), but zidovudine was the ARV most linked to ADRs (41.4%). The regression analysis showed increased risk of ADRs in singles and students in the univariate analysis and heterosexuals and homosexuals in multivariate analysis; and decreased risk in active workers. The present work shows the high prevalence of ADRs in the studied population and represents the first case-based study that describes the pharmacoepidemiology of a cohort of HIV-positive patients treated in Venezuela. PMID- 27382798 TI - [Molecular characterization of hepatitis C virus in patients referred to a reference laboratory of public health, University Hospital "Antonio Patricio de Alcala", Cumani, Venezuela]. AB - The World Health Organization estimates that approximately 170 million people are chronically infected with hepatitis C virus (HCV). This study evaluated the presence of antibodies against HCV by two immunoassays. HCV genotypes were analyzed by phylogenetic analysis of viral genome fragments amplified from the 5 'non-coding (5'NC) region and non-structural region 5b (NS5b), using reverse transcription and nested polymerase chain reaction (RT-PCR), in patients referred from January 2010 to February 2013 to the Reference Laboratory of Public Health, University Hospital "Antonio Patricio de Alcala". The prevalence of anti-HCV antibodies was 0.57% (17/3005), being the group of patients older than 41 years the most affected (0.9%). A total of 16 samples were found positive for HCV RNA by RT-PCR in the 5'NC region (16/17, 94%). Phylogenetic analysis of the 5'NC region allowed to identify the circulation of genotypes 2 and 1, and one genotype 3 and one 4. By phylogenetic analysis of the NS5b region, diverse subtypes of HCV genotype 2 were identified (2a, 2j and 2s). This finding is in accordance with previous studies that indicate that this genotype is relatively diverse in our country. PMID- 27382799 TI - [Evaluation of discriminatory power of molecular epidemiology techniques in Mycobacterium tuberculosis Venezuelan isolates]. AB - The techniques of spoligotyping and mycobacterial interspersed repetitive unit and variable-number tandem repeat typing with 24 loci (MIRU-VNTR-24), have been used to study the molecular epidemiology of tuberculosis. The aim of this study was: to evaluate the discriminative power of MIRU-VNTR 24 loci alone and in association with spoligotyping in clinical isolates of M tuberculosis in Venezuela; the allelic diversity of the 24 loci; and the discriminative power for the combination of 24 and 15 loci, 12 traditional loci (12t), those with higher allelic diversity and a new combination named 12inv. We analyzed one set of 104 strains of different lineages and a second set of 431 strains belonging to the Latin-America and Mediterranean lineage (LAM) that is predominant in Venezuela. The determination of allelic diversity showed that 4052, 2163b, 424 y 2996 are highly discriminative. Clustering rates of MIRU-VNTR 24 loci, spoligotyping and MIRU-VNTR combined with spoligotyping for 104 isolates were 18.27%, 71.15% and 14.4%, respectively, whereas with the 431 LAM strains the values were 43.2 %, 95.8% and 37.4%. MIRU-VNTR combinations of 15, 12inv and 4 loci were more discriminatory than 12t. Clustering rates for MIRU-VNTR 15 and 12inv loci coupled with spoligotyping in the 104 isolated was 21% and 23%, while for LAM strains was 52% and 46% respectively. The number of different genetics patterns for 15 and 12inv loci were similar. In conclusion, we propose the use of a small number of informative loci MIRU-VNTR coupled to spoligotyping to investigate the transmission of tuberculosis in Venezuela. PMID- 27382800 TI - Genetic diversity of hepatitis B virus and mutations associated to hepatocellular carcinoma in patients from Venezuela, with different stages of liver disease. AB - Globally, about 50% of liver cancer originates as a result of long term infection with hepatitis B virus (HBV), and some genotypes and mutations have been associated with an increased severity of infection. The aim of this study was to evaluate the genetic diversity of HBV in patients from Venezuela, with chronic infection, cirrhosis and hepatocellular carcinoma (HCC) and to compare the occurrence of mutations in all patient groups. Samples from patients with different pathologies of the liver, associated with HBV infection, were collected. The HBV S region was analyzed for genotype determination and, when available, the whole genome sequence was examined for mutations analysis. Genotype F was the most common genotype (87%). While the HBV subgenotype F3 was the most frequent genotype in the whole group of samples (44%), the subgenotype F2 predominated in HCC patients (56%). Mutations were more common in HCC and cirrhosis cases (p=0.01). The A1762T mutation was significantly associated with the advanced stage of liver disease (p=0.008). Additionally, mutations were more common in early stages of liver disease in HBV subgenotype F2-infected patients, and a significant association between this subgenotype and the emergence of T 1753C, A1762T, A1762T/G1764A (p=0.04) and C1773T (p=0.001) mutations in chronic patients was found, when compared to the HBV subgenotype F3. By comparing F2 with all other HBV subgenotypes, a positive association for the three basal core promoter (BCP) mutants (A1762T, A1762T/G1764A p=0.01, G1764A p=0.04) was found. These results suggest that the HBV subgenotype F2 might be associated to more severe forms of liver disease in comparison with the HBV subgenotype F3. PMID- 27382801 TI - [Superficial mycoses: casuistry of the Mycology Department of the Instituto Nacional de Higiene "Rafael Rangel", Caracas, Venezuela (2001-2014)]. AB - The superficial mycoses are very common infectious diseases and therefore are a frequent reason for medical consultation. The aim of this study was to determine the diagnostic frequency of superficial mycoses in the Mycology Department of the Instituto Nacional de Higiene "Rafael Rangel" during 14 years (2001-2014). A retrospective cross-sectional study was performed to review the mycological records of patients with presumptive diagnosis of superficial mycosis. Nails, hairs and epidermal scales were the processed samples. The identification of fungi was performed by macro and microscopic observation of colonies and biochemical and physiological tests, as required of the isolated agent. For the investigation of Malassezia spp. only direct examination was performed. Of the 3 228 samples processed, 1 098 (34%) were positive and their distribution according to the etiological agent was: dermatophytes 79.5%; 10.9% yeasts; non dermatophytes fungi 5.1% and 4.5% Malassezia spp. The most frequently isolated dermatophyte was Trichophyton rubrum Complex (70.1%), followed by T mentagrophytes complex (15.1%), Microsporum canis (9.4%) and Epidermophyton floccosum (4%). The most frequent ringworms Were: Tinea unguium (66.8%), followed by Tineapedis (16.4%) and Tinea capitis (8.1%). Candida parapsilosis complex (37.5%) was the most frequently isolated yeast and Fusarium spp. (53.6%) was the most isolated among non-dermatophyte fungi, followed by Aspergillus spp. (19.6%) and Acremonium spp. (10.7%). The identification of the etiological agent is essential to guide appropriate treatment. This study constitutes an important contribution to the knowledge of the epidemiology of superficial mycoses in our country. PMID- 27382802 TI - [Atypical leiomyoma in a patient with cutaneous leiomyomatosis and mutation of the enzyme fumarate hydratase]. AB - We report the case of a 56 year-old male with an atypical leiomyoma in the context of a cutaneous leiomyomatosis and a family history of uterine leiomyomatosis. The genetic study revealed a mutation in the gene for the enzyme fumarate hydratase, but he has not had any renal malignancy so far. Atypical leiomyoma is a rare tumor that usually presents as a single lesion and is exceptional in patients with cutaneous leiomyomatosis. The relation between fumarate hydratase enzyme mutations with multiple leiomyomas, uterine leiomyomatosis and an increased risk of developing kidney cancer is widely known. However, the role of these mutations in the development of atypical leiomyomas is still impossible to clarify given the few cases reported in the literature. PMID- 27382803 TI - [Adrenomedullin in the kidney: physiology and pathophysiology]. AB - Adrenomedullin (AM) is a potent vasodilatory 52-aminoacid peptide hormone, ubiquitous with multiple physiological effects which contribute to homeostatic responses. Significantly, it is distributed in the adrenal gland, lung, cardiovascular and renal system. The biological effects of AM are directly mediated by specific receptors as heterodimers composed of the calcitonin receptor-like receptor (CLR) and one of two receptor activity modifying proteins (RAMP2 or RAMP3). The CLR/RAMP2 (AM1 receptor) is more highly AM-specific than The CLR/RAMP3 (AM2 receptor). Plasma levels of AM are elevated proportionately to the increase in blood pressure and degree of renal damage in patients with hypertension; likewise, these levels are correlated with the degree ofheart and arterial hypertrophy. AM has renal vasodilatory, natriuretic and diuretic actions; increased glomerular filtration rate and renal blood flow. AM inhibits proliferation and reactive oxygen species generation in mesangial cells; also inhibits aldosterone secretion in the zona glomerulosa and endothelin-1 in vascular smooth muscle cells. Therefore, it is proposed as a new marker in various diseases, especially chronic renal failure. This disease presents compensatory hypertrophy of the glomeruli and mesangial proliferation, administration of AM reduces the levels of proteinuria, suggesting that AM has an important modulator role in blood pressure and could be a therapeutic option for chronic renal failure. PMID- 27382804 TI - [Contamination, endocrine disruptors and cancer]. AB - Since the mid-twentieth century, many species, very different from each other and located in all areas and comers of the planet, began presenting various alterations, many of which suggested to be related to endocrine disorders. Research has shown that such alterations were caused by exposure to various chemical contaminants that could affect the health and cause serious illnesses. Among them stands a diverse and large group of compounds, with very different chemical structures, capable of altering the hormonal balance, act at very low doses and with different mechanisms of action, that are called "endocrine disrupting chemicals". When released into the environment or as part of objects, food or medicines, constitute a major risk to animals and humans, which produces not only endocrine dysfunctions but also different cancers, which include the most common types. Despite the importance and significance of the impact of these compounds, they are not sufficiently known or understood, so the aim of this review is to show their origin and impact in the field of human health, highlighting their role as inducers of cancer, which has led to multiple clinical and biological investigations. PMID- 27382805 TI - [Present and future of therapy against hepatitis C]. AB - Around 3% of the human population is infected with hepatitis C virus (HCV) and 70 80% of these individuals develop a chronic infection. There is no vaccine available against HCV and up to 50% of the infected patients do not respond to standard therapy, based on the combination of interferon-alpha (IFN-alpha) and ribavirin. Recently, direct acting antiviral drugs against HCV have been made available for treatment, leading to a significant improvement in therapeutic success. In 2014, the U.S. Food and Drug Administration approved ledipasvir plus sofosbuvir to treat the chronic infection, the first IFN- and ribavirin-free approved treatment. With such treatment, the eradication of the disease would be feasible, although drug costs are high. Host target therapy represents an emerging alternative, based on the understanding of host factors involved in the HCV infection. This therapy might show at least two theoretical benefits, increasing the number of options for therapy and raising the genetic barrier for selection of resistant variants. New treatment regimens may consist of classical therapy combined with host target-based therapy, hopefully in a synergistic manner. PMID- 27382806 TI - PERIMORTEM CESAREAN DELIVERY. PMID- 27382807 TI - CONTINUOUS NON-INVASIVE ARTERIAL PRESSURE DEVICE AS AN ADJUNCT TO RECOGNIZE FLUCTUATING BLOOD PRESSURES DURING ELECTIVE CESAREAN SECTION UNDER SUBARACHNOID BLOCKADE (SAB). AB - BACKGROUND: Measuring non-invasive blood pressure (NIBP) in less than one minute intervals (STAT NIBP measurements) is not always feasible. Therefore, large number of undetectable hypotension episodes can only be recognized with continuous beat to beat monitoring of blood pressure, for example, by continuous non-invasive arterial pressure monitor (CNAP). OBJECTIVE: The purpose of the current study was to investigate whether CNAP correlates well with conventional intermittent oscillometric NIBP during elective cesarean sections under subarachnoid blockade (SAB) and whether CNAP based patient management results in improved immediate maternal vasopressor requirements and improved immediate fetal/neonatal outcomes compared with NIBP based patient management. MATERIALS AND METHODS: The CNAP finger cuff together with the CNAP arm cuff were placed on the same arm which also had the peripheral intravenous access.. On the contralateral arm the conventional NIBP arm cuff was placed. Study Group: The patients were managed by the anesthesia provider based on the CNAP monitor readings. Control Group: The patients were managed by the anesthesia provider based on the NIBP monitor readings. Results: The CNAP-based treatment (study) group had a statistically significant lower use of oxytocin and lower estimated blood loss than the NIBP-based treatment (control) group. The differences in incidences of vasopressors use and peri-operative nausea vomiting between study group and control group did not reach statistical significance. CNAP readings were more likely to be in systolic hypotensive phases (80mmHg) as compared to NIBP readings. CONCLUSION: Continuous non-invasive arterial pressure (CNAP) device may ONLY act as an adjunct to recognize fluctuating blood pressures during elective cesarean section under subarachnoid blockade (SAB). PMID- 27382808 TI - COMPARISON OF INDIRECT VIDEO LARYNGOSCOPES IN CHILDREN YOUNGER THAN TWO YEARS OF AGE: A RANDOMIZED TRAINEE EVALUATION STUDY. AB - BACKGROUND: Gaining proficiency with various airway management tools is an important goal for anesthesiology training. Indirect video laryngoscopes facilitate tracheal intubation in adults, but it is not clear whether these findings translate to children. This study evaluates the total time to successful intubation when performed by anesthesiology trainees using GlideScope Cobalt(r) video laryngoscopy (GlideScope), Storz DCI(r) video laryngoscopy (Storz), or direct laryngoscopy (Direct) in children <2 years old with normal airway anatomy. METHODS: Sixty-five children presenting for elective surgery were randomly assigned to undergo tracheal intubation using GlideScope, Storz, or Direct. Laryngoscopists were anesthesiology trainees in clinical anesthesia year >=2 who had proven basic proficiency with each laryngoscope on an infant airway manikin. Total time to successful intubation (TTSI, seconds), rate of successful intubation on first laryngoscopy attempt, and the change in intubation time from manikin to clinical settings were recorded. An intubation time difference >10 seconds was defined as clinically significant. RESULTS: TTSI was longer for Storz (42.1; 34.0 to 59.0) than for Direct (21.5; 17.0 to 34.3; p=0.002). We were not able to demonstrate a difference >10 seconds between the GlideScope and the other laryngoscopes. Median manikin intubation time was <10 seconds and increased significantly in the clinical setting for all laryngoscopes (all p <0.0001). CONCLUSIONS: Anesthesiology trainees completed manikin tracheal intubation rapidly with all laryngoscopes studied, but required a clinically significant longer time to tracheally intubate children <2 years. Our findings suggest in vivo training should be included to facilitate proficiency with device-specific intubation techniques. PMID- 27382809 TI - PERIPHERAL INTRAVENOUS CATHETER PROBLEMS IN INFANTS AND CHILDREN PRESENTING FOR ANESTHESIA AND SURGERY. AB - BACKGROUND: Anesthesia providers frequently rely upon in-situ peripheral intravenous catheters (IVs) during the perioperative care of pediatric patients. IV dysfunction can result in complications including inability to administer medications for resuscitation, extravasation of tissue-toxic medications, and incomplete induction of anesthesia. This study was performed to prospectively assess the frequency of IV dysfunction in children presenting for anesthesia care. METHODS: A survey of IV patency and integrity was completed in patients less than 18 years of age arriving at the preoperative holding area for anesthesia evaluation. Prior to the induction of anesthesia, an anesthesiologist examined the IV for patency and evidence of infiltration. Demographic information, catheter site and size, condition of skin, elapsed time since insertion, and hospital site of catheter insertion were recorded. RESULTS: Over a 14-month period, 108 IVs were evaluated in 106 patients. One or more problems were identified with 35% of the IVs. Problems included erythema or pain to palpation at insertion site (29%), difficulty with injection of saline (45%), pain on injection of saline (50%), infiltrate at insertion site (13%), no flow or poor flow to gravity (42%), and kinked catheter (11%). The frequency of IV dysfunction was higher in infants (50%), with 24 gauge catheters (59%), with lower extremity IVs (50%), and with IVs in place for more than 3 three days (75%). CONCLUSIONS: Approximately one-third of pre-existing IVs were dysfunctional in children presenting for anesthesia and surgery. Inspection for the integrity of the IV should occur prior to and during use, and a plan should be in place for readily replacing the IV in cases of dysfunction or for using an alternative route for the induction of anesthesia. PMID- 27382810 TI - COMPARISON OF INTRAOPERATIVE KETAMINE VS. FENTANYL USE DECREASES POSTOPERATIVE OPIOID REQUIREMENTS IN TRAUMA PATIENTS UNDERGOING CERVICAL SPINE SURGERY. AB - BACKGROUND: Postoperative airway compromise following cervical spine surgery is a potentially serious adverse event. Residual effects of anesthesia and perioperative opioids that can cause both sedation and respiratory depression further increase this risk. Ketamine is an N-methyl-d-aspartate (NMDA) receptor antagonist that provides potent analgesia without noticeable respiratory depression. We investigated whether intraoperative ketamine administration could decrease perioperative opioid requirements in trauma patients undergoing cervical spine surgery. METHODS: We retrospectively reviewed anesthesia records identifying cervical spine surgeries performed between March 2014 and February 2015. All patients received a balanced anesthetic technique utilizing sevoflurane 0.5 minimum alveolar concentration (MAC) and propofol infusion (50-100 mcg/kg/min). For intraoperative analgesia, one group of patients received ketamine (N=25) and a second group received fentanyl (N=27). Cumulative opioid doses in the recovery room and until 24 hours postoperatively were recorded. RESULTS: Fewer patients in the ketamine group (11/25 [44%] vs. 20/27 [74%], respectively; p = 0.03) required analgesics in the recovery room. Additionally, the total cumulative opioid requirements in the ketamine group decreased postoperatively at both 3 and 6 hours (p = 0.01). CONCLUSION: Ketamine use during cervical spine surgery decreased opioid requirements in both the recovery room and in the first 6 hours postoperatively. This may have the potential to minimize opioid induced respiratory depression in a population at increased risk of airway complications related to the surgical procedure. PMID- 27382811 TI - COMBINED BLOCK OF THE FEMORAL AND LATERAL FEMORAL CUTANEOUS NERVES UNDER ULTRASOUND FOR POST- OPERATIVE ANALGESIA IN PATIENTS UNDERGOING HIP SURGERY: A DOUBLE BLIND RANDOMIZED TRIAL. AB - BACKGROUND: Inadequate pain management of post-operative pain of patients undergoing hip surgery can result in morbidity and mortality complications. Anatomically, pain resulted from the incision site innervation (Lateral femoral cutaneous nerve) and the hip joint innervation mainly the femoral nerve. Adding femoral nerve blockade to the multimodal regimen for postoperative pain control after hip surgery has been described. METHODS: all 31 patients included in the study received preoperatively combined FN and LFCN block with Normal Saline 0, 9% (group I) or bupivacaine 0.5% (group II) randomly by using a previously generated continuous randomization list kept in a closed envelope. Pain control regimen consisted of Perfalgan 1g IV every 6 hours systematically and Dolosal 50 mg IM every 6 hours if needed (i.e. VAS > 4). Pain level was measured by using Visual Analogue Scale (VAS) for the first 24 hours.Time to the first request of analgesia and the total dose of dolosal were calculated. RESULTS: The number of patients who requested narcotics was significantly higher in group I (8) than group II (3), P=0,044; the total dose of dolosal used was significantly higher in group 1 (50 mg) than group II (9,375mg), P=0,0058. Time to the first request for analgesia was significantly lower in group I (6hrs +/- 5,12) as compared to Group II (21.3 hrs +/- [Arabic letters: see text]), P =0,043. CONCLUSION: In conclusion, FN and LFCN block when added to the standard regimen for postoperative pain management after hip surgery had a benefit in decreasing pain scores as well as opioid consumption. PMID- 27382812 TI - COMPARISON OF POSTOPERATIVE ANALGESIC EFFECT OF INTRATHECAL KETAMINE AND FENTANYL ADDED TO BUPIVACAINE IN PATIENTS UNDERGOING CESAREAN SECTION: A PROSPECTIVE RANDOMIZED DOUBLE-BLIND STUDY. AB - OBJECTIVES: To compare the analgesic efficacy of intrathecal Ketamine and fentanyl added to bupivacaine in patients undergoing cesarean section. METHODS: Ninety patients 18-40 years old were recruited in a prospective double-blinded, randomized way. Spinal anesthesia was performed in the three groups by using bupivacaine 10mg combined with 0.1mg/kg ketamine in group K, bupivacaine 10mg combined with 25 ug fentanyl in group F and bupivacaine 10mg combined 0.5 ml distilled water in group P. The time to first analgesic request, analgesic requirement in the first 24 hours after surgery, sensory and motor blockade onset time, duration of sensory and motor blockade, the incidence of adverse effects were recorded. RESULTS: The mean time to first analgesic request was longer in group K (296.80 +/- 32.46) compared to group F (277.87 +/- 94.25) and group P (235.43 +/- 22.35). The difference between group K and F (P = 0.504) was not significant but the difference between group K and group P (P <0.001) and group F and group P (P = 0.042) was significant. CONCLUSION: Addition of ketamine or fentanyl to spinal bupivacaine were equally effective in pain control after cesarean section and therefore, based on the specific conditions of patients, ketamine at concentrations mentioned earlier, could be a proper alternative to achieve postoperative analgesia PMID- 27382813 TI - EFFECT OF PREOPERATIVE INTRAVENOUS OXYCODONE ON LOW-DOSE ROPIVACAINE SPINAL ANESTHESIA COMBINED WITH INTRATHECAL FENTANYL. AB - BACKGROUND: Low-dose ropivacaine combined with intrathecal fentanyl can provide adequate anaesthesia with minimal haemodynamic variation. Preemptive analgesia can enhance analgesic effect of spinal anaesthesia without obvious side effects. AIMS: To assess the efficacy of preoperative intravenous oxycodone on transurethral resection of prostate (TURP) under 10 mg ropivacaine spinal anaesthesia combined with intrathecal 25 pg fentanyl. METHODS: Sixty patients undergoing TURP were randomly divided into two groups: Group o (n=30), in which the patients were administered 0.1 mg.kg-1 oxycodone intravenously 10 min prior to the operation for 2 min, and Group C (n=30) in which the patients were administered intravenously a similar volume of 0.9% saline. The participants were injected with hyperbaric 10 mg ropivacaine and 25 ug fentanyl intrathecally. The block characteristics, hemodynamic values, the tramadol consumption and adverse effects were analyzed. RESULTS: The peak level of sensory block was lower in Group C. Time to the first analgesic request and time to two-segment regression of sensory block were shorter in Group C. Fewer patients in Group 0 were given postoperative analgesics. CONCLUSION: Preoperative intravenous oxycodone can prolong analgesic effect of this method and postoperative analgesia. PMID- 27382814 TI - PENTAZOCINE VERSUS PENTAZOCINE WITH RECTAL DICLOFENAC FOR POSTOPERATIVE PAIN RELIEF AFTER CESAREAN SECTION- A DOUBLE BLIND RANDOMIZED PLACEBO CONTROLLED TRIAL IN A LOW RESOURCE AREA. AB - BACKGROUND: The unimodal approach of using pentazocine as post-cesarean section pain relief is inadequate, hence the need for a safer, easily available and more effective multimodal approach. AIM: To evaluate the effectiveness of rectal diclofenac combined with intramuscular pentazocine for postoperative pain following cesarean section. METHODS: In this double blind clinical trial, 130 pregnant women scheduled for cesarean section under spinal anesthesia were randomly assigned to two groups. Group A received 100mg diclofenac suppository and group B received placebo suppository immediately following surgery, 12 and 24h later. Both groups also received intramuscular pentazocine 30mg immediately following surgery and 6 hourly postoperatively in the first 24 h. Postoperative pain was assessed by visual analogue scale at end of surgery and 2, 12 and 24 h after surgery. Patient satisfaction scores were also assessed. RESULTS: One hundred and sixteen patients completed the study. Combining diclofenac and pentazocine had statistically significant reduction in pain intensity at 2, 12, and 24 hours postoperatively compared to pentazocine alone (p <0.05). No significant side effects were noted in both groups. The combined group also had significantly better patient satisfaction scores. CONCLUSION: The addition of diclofenac suppository to intramuscular pentazocine provides better pain relief after cesarean section and increased patient satisfaction. PMID- 27382815 TI - THE EFFECT OF A SINGLE DOSE OF MAGNESIUM SULPHATE AS AN ADJUVANT TO EPIDURAL BUPIVACAINE FOR INFRAUMBILICAL SURGERIES: A PROSPECTIVE DOUBLE-BLIND, RANDOMIZED CONTROL TRIAL. AB - CONTEXT: Epidural anesthesia provides the advantage of segmental blockade and many adjuvants have been added to shorten the onset of action, improve the quality of analgesia and prolong the duration of analgesia. Magnesium sulphate(MgSO4) by virtue of its anti-iociceptive property has been administered by various routes. AIM: To assess the effect of MgSO4 on the duration of onset of action of injection bupivacaine for epidural anesthesia in infraumbilical surgeries. MATERIALS AND METHODS: A prospective, double-blind, randomized control study was conducted in 40 patients. Group M received 15 ml of bupivacaine 0.5% + 1 ml of 50 mg MgSO4 and Group C received 15 ml of bupivacaine 0.5% + 1 ml of normal saline via epidural route. Onset time of the sensory and motor blockade were the primary outcomes studied. Highest level of sensory block, time for two segment regression, hemodynamic parameters, side effects were the secondary parameters. RESULTS: There was a significant difference between the groups in the mean onset time of sensory blockade at T8, 12.85 +/- 2.32 min in Group M and 16.75 +/- 1.74 min in Group C. Median level of sensory blockade was comparable. Mean onset time of motor blockade was 13.85 +/- 3.28 min in Group M and 23.25 +/- 3.35 min in Group C which was clinically and statistically significant. Time for two segment regression of sensory blockade was 95.75 +/- 11.84 min in Group M and 55.5 +/- 8.57 min in Group C which was significant. Hemodynamic parameters and side effects were comparable. CONCLUSION: Magnesium sulphate as an adjuvant provides rapid onset of epidural anesthesia and prolongs the duration of analgesia with minimal side effects. PMID- 27382816 TI - EFFECT OF DEXMEDETOMIDINE ON HEMODYNAMIC PARAMETERS DURING EXTUBATION. A PROSPECTIVE RANDOMIZED DOUBLE BLIND STUDY. AB - BACKGROUND: Extubation is known to produce significant hemodynamic disturbances. There is a need to avoid increase in heart rate and blood pressure in hypertensive and cardiac patients and in vascular, neuro and intraocular surgeries. AIMS: To study the ability of dexmedetomidine to attenuate the hemodynamic responses during extubation. MATERIALS AND METHODS: 80 patients of ASA Grade I-II aged 18-50 years received standard anesthesia. At the closure of skin incision, patients were randomly allocated to receive either dexmedetomidine 0.5 ug/kg (Group D) or saline placebo (Group C) intravenously over 10 minutes in a double-blind design. Heart rate (HR), systolic, diastolic and mean arterial pressures (SBP, DBP, MAP) were assessed before, during- and after extubation. Time to eye opening and extubation, sedation, complications such as coughing, laryngospasm, bronchospasm and desaturation were recorded. RESULTS: HR, SBP, DBP and MAP were comparable to basal values in group D at extubation and lower than baseline values post-extubation but significant increase was noted in group C (P <0.001). Time to extubation and eye opening were prolonged in Group D (P <0.001). Incidence of hypotension was more in group D (22%) but was transient. Incidence of coughing was lower in Group D than in group C (P <0.001). Patients in group D were more sedated for 30 minutes post extubation. CONCLUSION: Dexmedetomidine 0.5 ug/kg given before extubation attenuates hemodynamic reflexes during emergence from anesthesia without causing undue sedation, but prolongs time to extubation. PMID- 27382817 TI - PERI-ANESTHESIA ANAPHYLAXIS (PAA): WE STILL HAVE NOT STARTED POST-PAA TESTING FOR INCITING ANESTHESIA-RELATED ALLERGENS. AB - Anaphylaxis during anesthesia is uncommon. Diagnosis of peri-anesthesia anaphylaxis (PAA) requires anesthesia providers' vigilance for prompt diagnosis and treatment. In this case report, we present a challenging case with suspected PAA including its perioperative management, intensive care unit (ICU) course, and post-discharge follow-up. A 44-year-old female (body mass index = 26) presented for elective abdominal panniculectomy. Post-intubation, severe bronchospasm occurred that was non-responsive to nebulized albuterol and intravenous epinephrine. Continuous infusion of epinephrine was initiated. After aborting surgical procedure, the patient was transferred to ICU on continuous intravenous infusion of epinephrine. Venous blood sampling showed elevated troponin level. Echocardiography revealed ejection fraction of 25% suspicious of Takotsubo cardiomyopathy (mid cavitary variant). Tracheal extubation was only possible after three days. Subsequently, patient was discharged home with a cardiology follow-up appointment and a referral to an allergy specialist. Unfortunately at our institution (an academic university hospital in United States) along with neighboring institutions in near-by areas, the only allergy skin tests available are for local anesthetics and antibiotics, while neuromuscular blocking agents (NMBAs) cannot be tested (the suspected anaphylactic agent in our case was presumably rocuronium). In summary, PAA requires and responds to emergent diagnosis and immediate treatment; however there is still a long way to go to ensure post-PAA testing for inciting anesthesia-related allergens. PMID- 27382818 TI - SEVOFLURANE AS A CAUSE OF TORSADE DE POINTES IN PATIENT WITH THE LONG QT SYNDROME: Case Report. AB - Long QT syndrome (LQTS) is a rare condition that in certain circumstances can lead to severe and potentially lethal cardiac arrhythmia known as Torsade de Pointes (TdP). Inhalational anesthetics are among many medications and conditions known to prolong QT and thus potentially predispose the patient to TdP. Although studies have shown that sevoflurane should be safe for the healthy patients, the situation is unclear in patients with LQTS. We present a case of 14-year-old Caucasian female with the diagnosis of LQTS who developed TdP during sevoflurane inhalational induction. At the end, an anesthetic plan for patients with LQTS will be suggested. PMID- 27382819 TI - A CASE OF GRANISETRON ASSOCIATED INTRAOPERATIVE CARDIAC ARREST. AB - We report a case of intraoperative severe bradycardia that resulted in asystole and cardiac arrest shortly after (<2 min) intravenous granisetron 1mg for postoperative nausea and vomiting prophylaxis, that occurred in a female patient who underwent an elective total thyroidectomy. After two cycles of cardiopulmonary resuscitation and defibrillation, spontaneous circulation and sinus rhythm returned successfully. Postoperatively, the patient was diagnosed with a drug-induced long QT syndrome. At the time of the event, granisetron was the only medication administered. Furthermore, there was no reason to suspect electrolyte abnormalities. We explore the association of the onset of severe sinus bradycardia with the intravenous administration of granisetron. PMID- 27382820 TI - RETROGRADE INTUBATION VIA LARYNGEAL MASK AIRWAY IN A PAEDIATRIC PATIENT WITH FALLOT-TYPE VENTRICULAR SEPTAL DEFECT AND CLEFT PALATE DEFORMITY. AB - We report the case ofa pediatric patient with tetralogy of Fallot (TOF) and cleft palate deformity with difficult intubation in which a laryngeal mask airway (LMA) was used and converted into an endotracheal tube through retrograde intubation. The patient with TOF was scheduled for repair of the congenital bilateral cleft lip and palate. Inhalational induction with 4% sevoflurane was started. Conventional tracheal intubation was impossible because the patient had a difficult airway, and the procedure could cause severe cyanosis and respiratory distress. An LMA was inserted to maintain ventilation and anesthesia and to facilitate intubation. Retrograde intubation and a catheter mount were used to convert the LMA into a conventional endotracheal tube without difficulty. Airway management for patients with TOF and cleft palate deformity is not clear. Retrograde intubation permits replacing an LMA with an endotracheal tube. This method enables maintaining the airway until the LMA is exchanged with an endotracheal tube. This technique seems useful to facilitate difficult airway intubation in pediatric patients with TOF and cleft palate deformity. PMID- 27382821 TI - ANESTHETIC MANAGEMENT OF FEMORAL FRACTURE REPAIR IN A PATIENT WITH CERVICAL MYELOPATHY, AUTONOMIC DYSFUNCTION, AND DIFFICULT AIRWAY. AB - Spinal stenosis is a potentially serious condition that can lead to myelopathies and autonomic instability, both of which, as a result, may complicate anesthetic management. Additionally, neuraxial anesthesia appears to increase the risk of worsened neurological outcomes in this population. A 56-year-old female with spinal stenosis, autonomic dysfunction, and known difficult airway who required anesthesia for repair of a femur fracture is presented. After pre-operative arterial line and femoral block placement, an ultrasound guided subarachnoid block was safely placed. This supports the notion that in the appropriate setting, a safe, successful neuraxial blockade can be performed when a general anesthetic may be fraught with more risk. PMID- 27382822 TI - ANESTHETIC MANAGEMENT IN UNEXPECTED EXTRA- ADRENAL PHEOCROMOCYTOMA PRESENTING WITH THORACIC SPINAL CORD COMPRESSION. AB - A 52 yearold female presented with a thoracic paravertebral tumour causing spinal nerve root compression and lower limbs neurologic symptoms. The patient was scheduled to undergo thoracic decompression laminectomy and instrumentation. Markedly severe hemodynamic fluctuations happened during the manipulation of the tumor and continued after the tumor was removed. After multimodal antihypertensive therapy the vital signs were adequately managed and the surgery was successfully performed without complications. The patient was discharged without any sequelae ten days later. The pathology report indicated the diagnosis of extra-adrenal pheochromocytoma. Unexpected pheochromocytoma may lead to a fatal hypertensive crisis during surgery. For anesthesiologists and surgeons who encounter an unexpected hypertensive crisis during surgery, undiagnosed pheochromocytoma should always be considered. PMID- 27382823 TI - ANESTHETIC MANAGEMENT OF AORTIC VALVE REPLACEMENT IN A MYASTHENIA GRAVIS PATIENT, THE ERA OF A NEW REVERSAL. PMID- 27382824 TI - PATIENT-VENTILATION ASYNCHRONY CAUSING NEGATIVE PRESSURE PULMONARY EDEMA IN AN INTUBATED OBESE PATIENT. AB - Negative pressure pulmonary edema is a potentially life-threatening condition that may occur when a large negative intrathoracic pressure is generated against a 'physically' obstructed upper airway during emergence from anesthesia. We report a 35 year old male patient who is morbidly obese and undergoing laparoscopic gastric bypass who developed negative pressure pulmonary edema without any evidence of a 'physical' upper airway obstruction. In our patient, the negative pressure pulmonary edema occurred after complete reversal of neuromuscular blockade and during manual positive pressure ventilation with the endotracheal tube still in place and in the presence of an oral airway. Since the patient was still intubated and had an airway in place with no possibility for physical obstruction, we speculate that the occurrence of the negative pressure pulmonary edema was mainly due to a 'functional' obstruction secondary to the severe patient-ventilation asynchrony that ensued upon reversal of the neuromuscular blockade. PMID- 27382825 TI - EFFECT OF YOKUKANSAN, JAPANESE HERBAL MEDICINE, ON PHANTOM-LIMB PAIN. PMID- 27382826 TI - SIMULATION LAB: "A CONTEMPORARY MEDICAL ESSENTIAL". AB - Simulation-based medical education (SBME) and simulation-based mastery learning (SBML) has become well-established in undergraduate and graduate medical, nursing and allied healthcare training programs. Although still in its relative infancy, the use of hi-fidelity simulation to train students in a variety of health related professions is becoming a foundational cornerstone in program curriculum in the United States and, increasingly, in the international circle. The entire investment return resulting from the inclusion of simulation training labs in healthcare programs has just begun to be realized. The future is bright for this approach to education and healthcare to become an essential tool in the resource education box for colleges, universities, hospitals and research facilities as they serve the mission of training healthcare professionals to meet the growing needs of aging populations. PMID- 27382827 TI - [Malignized dermoid cyst of the ovary]. AB - Mature germ cell derived cystic teratoma of the ovary, i.e. dermoid cyst, is a common ovarian neoplasm, seldom progressing to malignancy. Malignized dermoid cyst is most commonly diagnosed in a woman of approx. 50 years of age, either during or after an operation. Owing to the rarity of the disease, the lines of treatment are based on retrospective series of cases. PMID- 27382828 TI - [Novel approved form of treatment for colonic cancer with peritoneal metastases - radicality-aimed surgery combined with hyperthermic intraperitoneal chemotherapy]. AB - Carcinomatosis occurs in almost 10% of colonic cancer patients, whereby the five year survival rate on cytostatic chemotherapy is approx. 13% at best. For patients having carcinomatosis restricted to a fairly small area, surgical removal of peritoneal metastases combined with hyperthermic intraperitoneal chemotherapy (HIPEC) may be a curative procedure. The treatment has resulted in a five-year life expectancy of 30 to 35% for selected patients. The treatment is, however, associated with significant morbidity and even mortality. Colorectal cancer patients diagnosed with restricted peritoneal carcinomatosis should be referred to an assessment for HPEC treatment. PMID- 27382829 TI - [Pregnancy contraception (Current Care Guideline)]. AB - There are no age limits for the start or use of contraception. Prior gynecological examination or cervical smear is not needed. Condom is the only method that protects from sexually transmitted diseases. An increase in the risk of venous thromboembolism (VTE) is associated only with combined contraceptives. However, the risk is remarkably higher with pregnancy, puerperium or with smoking. The most effective reversible methods are intrauterine devices (IUD) and implants, as these do not depend on daily memory. Natural family planning methods are not reliable, and effective contraception should be easily available for all at all times. PMID- 27382830 TI - [Drug therapy and the most common drugs for childhood psychiatric disorders]. AB - Psychotropic drugs are more commonly prescribed for children, although scientific evidence about psychotrophic medication and long-term effects thereof in children is scarce. The drugs are often used off-label. ADHD drugs, antipsychotics and antidepressants and melatonin are the most commonly used drugs. ADHD medication possesses the most established status. Antipsychotic drugs are utilized for the treatment of psychoses, bipolar disorder, and conduct disorder symptoms in particular. Antidepressants are utilized for the treatment of childhood depression and anxiety disorders, melatonin for the treatment of children's sleep problems. Drug therapy should always be carried out as part of other psychiatric therapy. PMID- 27382831 TI - [Infant psychiatry - more reality than tale]. AB - In early childhood, the ability of the parent and the child to adapt to each other's needs during early interaction is essential for a healthy mental development.The parent's ability to carry out adequate early interaction may be compromised because of various problems. Positive, shared emotional experiences with the parent can protect the child's mental health. Severe or prolonged problems in baby care, interaction or behavior of the infant may result in the development of a psychic disorder in the infant. Infant psychiatric diagnosis and treatment plan are based on clinical examination of the child and the family and evaluation of the need for support. PMID- 27382832 TI - [Children's disruptive behavior]. AB - During normal development, a child learns to regulate her/his aggressions and follow the social norms of her/his community.This learning takes place in interaction with the environment. Risk factors associated with the child, parenthood and environment underlie the disruptive behavior. If a child of preschool/school age exhibits age group deviant difficulties in the management of aggression, defiant, rule-breaking behavior or difficulties in social relationships, there is every reason to get worried and to evaluate the child's symptoms and situation. The earlier the support and therapy is provided, the better are the possibilities to influence the prognosis of conduct disorders. PMID- 27382833 TI - [Are programs supporting parenthood skills effective in the prevention and reduction of conduct disorders and problems of childhood?]. AB - In this systematic review it will be evaluated whether parent-targeted programs teaching positive methods of upbringing and interaction are effective in the reduction and prevention of conduct disorders and behavioral problems in children belonging to a risk group. Altogether 29 European studies on parent-targeted programs were selected for the review. Most of the examined methods were based on the social learning theory and the cognitive behavior theory. The majority of the studies proved that long-term programs of 8 to 20 weeks'duration are effective in the reduction of behavioral problems and conduct disorders of childhood. PMID- 27382834 TI - [Psychological well-being during pregnancy - early roots of the child's mental health?]. AB - The conditions during pregnancy may influence the child's subsequent well-being via developmental programming. On the other hand, recurrence or continuation of the harmful exposure at a later stage during development may be more essential. The parent's mental disorder is one of the best known risk factors potentially affecting the mental health of the child. The mother's depressive and anxiety symptoms during pregnancy have been found to be predictive of symptoms in the young person and in the adult. Regarding the risk of disorder, the recurrence of the exposure to psychological symptoms and accumulation of other risk factors at a later stage of development seem, however, to be more important. PMID- 27382835 TI - [Twenty years' psychiatric treatment path]. AB - Treatment paths in psychiatry may extend from infancy to old age, particularly in neuropsychiatric patients. In the diagnostics and treatment it is important to consider the variations in the symptoms and focuses of rehabilitation during the different periods of the life cycle. Good care and its provision require a perspective extending through the lifespan and assurance of continuity. In our case report we describe a treatment path of 20 years' duration of our neuropsychiatric patient PMID- 27382836 TI - [Not Available]. PMID- 27382837 TI - [Not Available]. PMID- 27382838 TI - [Not Available]. PMID- 27382839 TI - Education in Agricultural Health. PMID- 27382840 TI - Editor's Remarks. PMID- 27382841 TI - [In acute appendicitis quickly into surgery]. PMID- 27382842 TI - [Will the LDL target value soon become zero?]. PMID- 27382843 TI - [Malpractice complaints threaten good medicine]. PMID- 27382844 TI - [Not Available]. PMID- 27382845 TI - [Not Available]. PMID- 27382846 TI - [Diseases of hunger: Mexico 1915]. AB - 1915 was a terrible year for Mexican people. After dictator Huerta's fall, fratricide fighting involved diverse revolutionary groups. Mexico City was assaulted and occupied successively by different armies and, following the war came hunger and epidemics. Many people died from starvation, 30 to 40 every day in July and August. In this paper I review the medical texts written by physicians involved in the treatment of these patients. The main were E. Landa, M. Torroella and F. de P. Miranda and all of them concurred in the observation of important edema increasing to become generalized, important anemia and a watery aspect of the blood, facts that determine the term edema employed to characterize this disease. PMID- 27382847 TI - [Developments in medical units. 1915]. AB - In 1915 the political, economic, and social instability initiated the destruction of medical units; they had no administrative bases and they lacked the resources. However, needs encouraged that structures arose to meet the wounded, fractured, and traumatized, called "blood" hospitals and so-called crosses and sanitary trains. PMID- 27382848 TI - [Military medicine in Mexico in 1915]. AB - As a part of the symposium titled "Mexico in 1915, Epidemics, Hunger, and Medical Assistance", presented at the National Academy of Medicine on August 5, 2015, this section will underscore the most important and transcendent facts inherent tot he military medicine and surgery that happened during the turmoil of the year 1915. PMID- 27382849 TI - [Conclusions]. PMID- 27382850 TI - On Universal Health Coverage. PMID- 27382852 TI - The Editors respond. PMID- 27382851 TI - Express concerns about the Spanish translation of The Lancet's Series entitled Universal health coverage in Latin America. PMID- 27382853 TI - Remarks at the Annual Conference of the Food and Drug Law Institute. PMID- 27382854 TI - Who to Sue and Where in ANDA Litigation: Personal Jurisdiction Post-Daimler. AB - Historically, courts have afforded patent holders broad discretion to choose where to sue Abbreviated New Drug Application (ANDA) filers. Patent holders' assertions of jurisdiction have typically rested on general personal jurisdiction theories, frequently based on an ANDA filers' conduct within the state, including sales, submission to previous lawsuits, and assignments of agents to accept service of process. Consequently, manyANDA cases have taken place in the Districts of Delaware or New Jersey, or where the patent holder is incorporated, despite the ANDA filer's incorporation in a different state. However, since the Supreme Court's decision in Daimler AG v. Bauman, options for the exercise of personal jurisdiction over ANDA filers have narrowed. This article examines what Daimler means for future ANDA filers, and highlights how many patent holders have failed to take this change into account. PMID- 27382855 TI - Substantial Equivalence Premarket Review: the Right Approach for Most Medical Devices. AB - The Food and Drug Administration (FDA)'s 510(k) program based upon substantial equivalence review is by far the dominant pathway to market among medical devices requiring premarket review. Substantial equivalence review has been much criticized, but this article concludes that it is a powerful regulatory tool allowing FDA to appropriately ensure that the broad range of moderate risk devices meet the statutory requirement of reasonable assurance of safety and effectiveness. The article examines substantial equivalence review in detail, looking at its historical development, the operative legal framework, the specific decision steps FDA follows to reach a substantial equivalence determination, and the strengths of the system in fostering efficiency, predictability, and adaptability in the premarket review of medical devices. The article rebuts the Institute of Medicine's call to scrap substantial equivalence review, and rebuts another critic's finding that substantial equivalence review results in a disproportionate share of serious recalls. The article suggests that a better public 510(k) database would improve the predictability of substantial equivalence review. The article concludes by calling for targeted reform of a basically sound system rather than wholesale condemnation as critics have suggested. PMID- 27382856 TI - Chinese Outbound Investments in the Food Sector: Hungry for Much More! AB - This article analyses in its first part the almost dramatic increase of Chinese outbound investments in recent years with a special focus on the food industry. The second part outlines China's legal framework that has governed Chinese outbound investments over the past decade. In its main part this article explores recent steps to liberalize China's economy and assesses how the dismantling of existing restrictions will impact on Chinese investments overseas. It forecasts rather wide-ranging consequences for the non-Chinese food industry as food enterprises have become highly-sought after targets of Chinese outbound investment activities. PMID- 27382857 TI - GMO Reignited in Science but Not in Law: A Flawed Framework Fuels France's Stalemate. AB - Following a statement released by a multitude of prominent scientists contesting the idea that there is a consensus on the safety of genetically modified organisms ("GMO"), this article addresses the European Union's ("EU") GMO regulatory framework, which has reluctantly permitted France to maintain an illegal ban on. MON8 10 for over a decade now. It notes that while the statement did nothing more than reignite the debate on GMO, much could and should be done to improve the framework to accommodate for the lack of true scientific understanding about the effects of GMO. This article identifies the specific areas of weakness in the EU GMO regulatory framework and recommends specific alterations. It concludes that although France's MON810 ban is illegal under existing law, the country's fears are neither unfounded nor unsupported and that the EU should work to alter its existing legal structure to parallel today's scientific uncertainty regarding GMO safety. PMID- 27382858 TI - Compensating Pharmaceutical Injuries in the Absence of Fault. AB - Adverse drug events cause significant injuries to consumers. Between half and three-quarters of these injuries are uncompensated under tort law because they are not due to negligence or fraud. This article argues that fundamental fairness and sound economics favor holding manufacturers of pharmaceutical products financially responsible for pharmaceutical injuries unless there is clear fault by another party. It reviews the experience of vaccine and pharmaceutical injury compensation programs internationally. It proposes the creation of an administrative compensation system for the United States that would compensate pharmaceutical injuries. PMID- 27382859 TI - "You Say Tomato, I Say Solanum Lycopersicum Containing Beta-ionone and Phenylacetaldehyde": an Analysis of Connecticut's GMO Labeling Legislation. AB - "You Say Tomato, I Say Solanum Lycopersicum Containing Beta-ionone and Phenylacetaldehyde" discusses the importance of requiring labels on products that contain genetically modified organisms, focusing on Connecticut's GMO Labeling statutes, as it is they are the first of their kind in the nation. The article will compare Connecticut's law to the legislation found in Australia, highlighting the positive aspects of Connecticut's bill and identifying its key weaknesses, namely the "trigger clause" found in the statute. Part I will provide an overview of Genetic Modification and provide a brief history of Biotechnology. It will also provide a brief overview of the federal regulatory framework in biotechnology, as well as evaluate the United States Food and Drug Association's role of regulating genetic modification. Part I will conclude by discussing how the American public has shown that labeling GMOs is important, and something that should occur. Part II of this article will explore Connecticut's recent legislation requiring labels on products that contain GMOs. Part III will explore Australia's legislation requiring labels on products containing GMOs, comparing Australia's law to Connecticut's legislation. PMID- 27382860 TI - Talking about end-of-life care. PMID- 27382861 TI - Education, certification, and professional membership can help with career goals. AB - For the professional nephrology nurse, the interplay of certification, education, and professional association membership go hand-in-hand. The association provides the foundation, networking, and educational opportunities; certification validates skills and expertise; and education challenges and inspires the nurse to keep moving forward. PMID- 27382862 TI - Financial incentives may spur donation. PMID- 27382863 TI - Baxter begins trial with HHD machine. PMID- 27382864 TI - Providing supportive care to patients with kidney disease. AB - While it may never be "easy" to face these issues with patients, families, and caregivers, CSCKP hopes the best practices and tools outlined in this article, also available at www.kidney-supportivecare.org, will be helpful to renal professionals in providing quality supportive and end-of-life care to their patients. Encouraging and participating in shared decision making with patients and their loved ones can help all involved create an approach to care with which everyone is comfortable. The relationships formed through shared decision making will help keep the lines of communication open, which is essential as needs and prognosis change. This type of health care provider/patient relationship may also encourage patients to share more about their symptoms, as not all patients are forthcoming about their symptoms or pain, and thereby facilitate better assessment and treatment by clinicians. Working with a palliative care specialist may be necessary when symptoms become more challenging to manage and referral to hospice may need to be considered. Helping patients, families, and caregivers understand their options, assisting them in completing advance care plans, and ultimately respecting their wishes are all encompassed within the delivery of patient-centered care. PMID- 27382865 TI - NICE swallows the hard pill of cancer drug calls. PMID- 27382866 TI - THE PROVIDER DEFICIT IS NEARER L4BN THAN L3BN. PMID- 27382867 TI - SWEET DRINKS TAX HAS A SOUR AFTERTASTE. PMID- 27382868 TI - Integrated care. Fostering pride in care with the 'three Ps'. PMID- 27382869 TI - IS PAPERLESS ON A TEAR? PMID- 27382870 TI - Ready or not, the bundled-payment challenge is about to start. PMID- 27382871 TI - Will the Anthem-Express Scripts battle change the PBM landscape? PMID- 27382872 TI - What happened to the innovation and competition Zarxio was supposed to spark? PMID- 27382873 TI - ACA repeal more difficult as U.S. gets used to popular provisions. PMID- 27382874 TI - HHS amps up vendor HIPAA audits. PMID- 27382875 TI - Why patients still need EMTALA. PMID- 27382876 TI - Genome sequencing rated top advance of past 40 years. PMID- 27382877 TI - A sputtering jobs machine. PMID- 27382878 TI - Challenges in healthcare risk management driving innovative, evidence-based solutions. PMID- 27382879 TI - Rewarding patients with loyalty points. PMID- 27382880 TI - 'Anybody who studies quality will tell you that variation is the absolute enemy of quality'. PMID- 27382881 TI - Porn and the threat to virility. The first generation of men who grew up with unlimited online porn sound the alarm. PMID- 27382882 TI - Special deals, circumstances propel healthcare CEO pay. PMID- 27382883 TI - Despite rough 2015, not all healthcare execs see drop in pay. PMID- 27382884 TI - CMS unveils Primary Care Plus. PMID- 27382885 TI - Quest, LabCorp forge divergent paths to hospital lab deals. PMID- 27382887 TI - Personal experiences drive chairman of N.J. medical center board. PMID- 27382886 TI - Dr. Benjamin's successful advocacy targeting population health. PMID- 27382888 TI - From 'horror show' to community resource: Evans aids revival of Roseland Hospital. PMID- 27382889 TI - Leading a shift in how healthcare providers and customers relate. PMID- 27382890 TI - PATIENT QUALITY PLAYING BIGGER ROLE IN FOR-PROFIT EXEC BONUSES. PMID- 27382891 TI - CMS' bold gamble on primary care. PMID- 27382893 TI - Better scheduling through math. PMID- 27382892 TI - Studying what works, doesn't work in health insurance reform. PMID- 27382894 TI - 'We have a long way to go yet on patient safety'. PMID- 27382895 TI - Ransomware scare: Will hospitals pay for protection? PMID- 27382896 TI - Florida, California lawmakers target unexpected medical bills. PMID- 27382897 TI - Paying patients for saving money. PMID- 27382898 TI - HOSPITALS DISCOVER THEIR INNER VENTURE CAPITALIST. PMID- 27382899 TI - Big data yield new hopes, challenges in cancer care. PMID- 27382900 TI - Shake-up to survive. PMID- 27382901 TI - Medicaid reforms helping to drive value-based payment. PMID- 27382902 TI - Primary-care practitioners will be key players in the value-based transformation of healthcare. PMID- 27382903 TI - Getting a leg up on bundles. PMID- 27382905 TI - STPs must not become expensive door stops. PMID- 27382904 TI - 'Turnaround was job one. Now we are moving forward'. PMID- 27382906 TI - DEVOLUTION AND REFORMS MUST MOVE IN TANDEM. PMID- 27382907 TI - MAKE IMPROVEMENT ACCESSIBLE TO ALL. PMID- 27382908 TI - MAKING IT HAPPEN IN GLASGOW. PMID- 27382909 TI - Making legal advice a clinical department. PMID- 27382910 TI - 'How can we do this better?'. PMID- 27382911 TI - HOW TO AVOID GETTING BURNT. PMID- 27382912 TI - Antidepressants and cardiovascular risk. PMID- 27382913 TI - NEURASTHENIA IN WAR. PMID- 27382914 TI - Diagnosing young onset dementia can be challenging. AB - Although the risk of developing dementia increases with age, onset can be as early as the third or fourth decade of life. Genetic influences play a more important role in younger than in older people with dementia, so young onset dementia may cluster in families. Diagnosing young onset dementia is challenging. The range of possible presenting features is broad, encompassing behavioural, cognitive, psychiatric and neurological domains, and symptoms are often subtle initially. Frequently the complaints are misattributed to stress or depression, and the patient is falsely reassured that they are too young to have dementia. The most common causes of young onset dementia are early onset forms of adult neurodegenerative conditions and alcohol. Vascular dementia is the second most common cause of young onset dementia after Alzheimer's disease. Conventional vascular risk factors may be absent and diagnosis relies on imaging evidence of cerebrovascular disease. Obtaining a detailed history remains the most important part of the workup and usually requires corroboration by a third party. Undertaking a basic neurological examination is also important. Those with suspected young onset dementia should be referred to a neurology-led cognitive disorders clinic where available as the differenti diagnosis is considerably broader tha in older adults and requires specialist investigation. PMID- 27382915 TI - Be vigilant for post-traumatic stress reactions. AB - Most people experience at least one potentially traumatic event (PTE) during their life. Many will develop only transient distress and not a psychological illness. Even the most inherently horrific event does not invariably lead to the development of a psychological disorder while an individual with sufficient vulnerabilit may develop post-traumatic stress disorder (PTSD) after what appears be an event of low magnitude. The diagnosis of PTSD differs fro most psychiatric disorders as it includes an aetiological factor, the traumatic event, as a core criterion. The DSM 5 core symptoms of PTSD are grouped into four key symptom clusters: re-experiencing, avoidance, negative cognitions and mood, and arousal. Symptoms must be present for at least one month and cause functional impairment. PTSD patients can avoid engaging in treatment and assertive follow-up may be necessary. PMID- 27382916 TI - Managing patients with hidradenitis suppurativa. AB - Hidradenitis suppurativa affects the apocrine-bearing areas of the skin. The onset is variable but usually occurs in the second and third decades of life, coinciding with development of the apocrine glands. The condition is characterised by painful, inflammatory papules and nodules which frequently progress to form abscesses, sinus tracts and hypertrophic scars. Bacteria are not felt to have a primary role in lesion formation, and abscesses are often sterile. The diagnosis of hidradenitis suppurativa is clinically based, without a specific diagnostic test. The most important non-genetic factors implicated in hidradenitis suppurativa are obesity and smoking. Locally recurring lesions can be treated surgically and more widespread disease may be better managed with a combination of medical treatment and surgery. PMID- 27382917 TI - Careful assessment the key to diagnosing adolescent heel pain. AB - The most common cause of adolescent heel pain is calcaneal apophysitis also known as Sever's disease. The condition may occur in adolescent athletes, particularly those involved in running or jumping activities, during the pubertal growth spurt. The mean age of presentation in Sever's disease is ten, (range 7-15). It presents with posterior heel pain that is worse with activity and relieved by rest in most cases. Sever's disease, Osgood Schlatter's disease (tibial tuberosity) and Sinding-Larsen Johansson syndrome (distal patella) are all overuse syndromes brought about by repetitive submaximal loading and microtrauma. They are, however, entirely self-limiting and resolve at skeletal maturity or earlier. Careful assessment is required to differentiate them from other rare pathologies. Achilles tendinitis is rare under the age of 14. As in Sever's disease, it may occur in jumping athletes, those who suddenly increase their sporting activities and in individuals with relative gastrosoleus tightness. It may also occur in those with inflammatory arthropathies and merit rheumatological investigation if there are other suggestive signs or symptoms. Benign and malignant tumours of the adolescent calcaneus are extremely rare In a unilateral case, atypical features such as night pain or absence of a precipitating activity should raise the index of suspicion. There may be localised swelling and bony expansion. PMID- 27382918 TI - A lesson from a patient. PMID- 27382919 TI - Allergic Conjunctivitis and the Associated Risk of Migraine Among Children: A Nationwide Population-based Cohort Study. AB - PURPOSE: To investigate the risk of migraine in children with allergic conjunctivitis (AC). METHODS: In this population-based cohort study, 309 138 children with AC and 309 138 non-AC controls were included between 2000 and 2007. By 2008 end, the incidences of migraine in both cohorts, and the AC-to-non-AC cohort hazard ratios (HRs) were measured. RESULTS: The incidence of migraine during the study period was 1.92-fold higher in the AC cohort than in the non-AC cohort. The risk was greater for boys with AC and children aged <6 years. The mean time-interval between physician-diagnosed AC to physician-diagnosed migraine was 3.67 years (SD = 2.19).The risk of migraine development in the AC cohort increased with follow-up time and was highest during 4-5 years after AC diagnosis. The children with AC more likely had migraine without than with aura. CONCLUSIONS: Children with AC had a higher incidence and subsequent risk of migraine. PMID- 27382920 TI - Metal-Free Visible Light-Mediated Photocatalysis: Controlling Intramolecular [2 + 2] Photocycloaddition of Enones through Axial Chirality. AB - Atropisomeric enone-imides and enone-amides featuring N-CAryl bond rotation were evaluated for intramolecular [2 + 2] photocycloaddition. Straight addition product was observed over cross-addition product with good control over reactivity. The atropselectivity was found to be dependent on the substituent on the aryl ring. Substitution-dependent atropselectivity was rationalized on the basis of a divergent mechanistic pathway. PMID- 27382921 TI - Potentiation of antifungal effect of a mixture of two antifungal fractions obtained from Baccharis glutinosa and Jacquinia macrocarpa plants. AB - The aim of the present work was to evaluate the effect of mixtures of antifungal fractions extracted from Baccharis glutinosa and Jacquinia macrocarpa plants on the development of the filamentous fungi Aspergillus flavus and Fusarium verticillioides. The minimal inhibitory concentration that inhibited 50% of growth (MIC50) of each plant antifungal fraction was determined from the percentage radial growth inhibition of both fungi. Binomial mixtures made with both plant fractions were used at their MIC50 to determine the Fractional Inhibitory Concentration index (FIC index) for each fungus in order to evaluate their synergistic effect. Each synergistic mixture was analyzed in their effect on spore germination, spore size, spore viability, mitotic divisions, hyphal diameter and length, and number of septa per hypha. Some antifungal mixtures, even at low concentrations, showed higher antifungal effect than those of the individual antifungal fraction. The FIC indices of mixtures that showed the highest antifungal activity against A. flavus and F. verticillioides were 0.5272 and 0.4577, respectively, indicating a synergistic effect against both fungi. Only 12% and 8% of the spores of A. flavus and F. verticillioides, respectively, treated with the synergistic mixtures, were able to germinate, although their viability was not affected. An increase in the number of septa per hypha of both fungi was observed. The results indicated that the synergistic mixtures strongly affected the fungal growth even at lower concentrations than those of the individual plant fractions. PMID- 27382922 TI - Patterns of Recurrence in Upper Tract Transitional Cell Carcinoma: Imaging Surveillance. AB - OBJECTIVE: The objective of our study was to evaluate recurrence patterns of upper tract transitional cell carcinomas (UT-TCCs) after radical nephroureterectomy (RNU). MATERIALS AND METHODS: Sixty-eight patients (mean age, 78 years; 34 men and 34 women) with UT-TCC after having undergone RNU from 2001 to 2008 were included in this study. Radiologic examinations and clinical notes were reviewed to record tumor location, tumor morphology, histologic T stages and grades, lymphovascular invasion (LVI) status, and surgical procedures. Five-year imaging and clinical follow-up (2001-2013) findings were noted at 3, 6, 12, 18, 24, 36, 48, 60, and more than 60 months after RNU for recurrence pattern and tumor-free survival. Kaplan-Meier survival curves and Cox regression models were used to assess tumor-free survival and to perform a multivariate analysis. RESULTS: Forty-one postoperative recurrences were noted in 20 patients. The mean time to relapse was 16 months, and time to relapse ranged from 1 to 66 months. Tumor site (multifocal lesions involving both renal collecting system and ureter), tumor morphology (mass), T stage (muscle invasion [T2-T4]), histologic grade (grade 3), and the presence of LVI were identified as risk factors for postoperative recurrence in UT-TCC. T stage was the only independent risk factor. CONCLUSION: Urinary tract, lymph node, liver, bone, and lung recurrences were common in patients with UT-TCC and were detected most frequently at 3-24 months. Tumor site, tumor morphology, T stage, grade, and LVI status were associated with recurrence after RNU. T stage was the only independent predictor of tumor-free survival. Close surveillance for extra-urinary tract recurrences in high-risk groups and a shorter-interval follow-up of the urinary tract in low-risk patients with adjuvant chemotherapy are recommended. Identifying recurrence patterns in UT TCC can aid in planning an effective tailored imaging surveillance strategy. PMID- 27382923 TI - Assessment of fatigue in routine care on a Multidimensional Health Assessment Questionnaire (MDHAQ): a cross-sectional study of associations with RAPID3 and other variables in different rheumatic diseases. AB - OBJECTIVES: To characterise associations of fatigue with other variables within a multidimensional health assessment questionnaire (MDHAQ) in routine care of patients with different rheumatic diagnoses. METHODS: All patients complete MDHAQ, which includes fatigue on a 0-10 visual analogue scale (VAS), and routine assessment of patient index data (RAPID3), a composite of function, pain, and patient global. Physicians complete a RheuMetric checklist which includes 4 VAS for overall global status (DOCGL), inflammation, damage, and distress. Median score for fatigue and other MDHAQ and RheuMetric scores were compared in 4 diagnosis groups: rheumatoid arthritis (RA), osteoarthritis (OA), systemic lupus erythematosus (SLE), and fibromyalgia (FM), using a Kruskall-Wallis test. Associations of fatigue with other variables were analysed using Spearman correlations and multivariate regressions. RESULTS: 612 patients were included: 173 RA, 199 with OA, 146 with SLE, and 94 with FM. Median fatigue was significantly higher in FM (7) than in RA (4), OA (5), and SLE (5). Fatigue was correlated significantly with all other MDHAQ scores, at higher levels in RA and SLE versus OA and FM. Fatigue was correlated significantly with DOCGL in RA, OA, SLE, but not FM. In multivariate analyses, fatigue scores were explained independently by higher pain and symptom number in RA; lower age and higher symptom number in OA; only higher pain in SLE; and none of the variables in FM. CONCLUSIONS: Fatigue is common in rheumatic diseases and strongly associated with higher pain and number of symptoms. The MDHAQ provides a useful tool to assess fatigue in clinical settings. PMID- 27382924 TI - Lipoma arborescens arising in the extra-articular bursa of the knee joint. AB - Lipoma arborescens arising in the extra-articular bursa of the knee joint is extremely rare. We describe an 11-year-old boy who complained of a gradual swelling mass of the lateral knee joint. Magnetic resonance imaging (MRI) showed a high signal intensity tumor on T1- and T2-weighted images with a thickened septa and nodular lesion that showed low signal intensity. The radiologist suggested the possible differential diagnosis of well-differentiated liposarcoma. At operation, the tumor was found under the iliotibial tract and was not in contact with the knee joint. Histopathologically, this lesion was diagnosed as lipoma arborescens arising in the extra-articular bursa of the knee joint. On MRI, the appearance of lipoma arborescens arising in the extra-articular bursa of the knee joint differed from that of conventional intra-articular lipoma arborescens. In this report, we describe a case of extra-articular lipoma arborescens of the knee joint bursa and discuss the diagnosis and etiology. PMID- 27382925 TI - Lesion of the hip abductor mechanism. AB - INTRODUCTION: The disruption of the abductor muscles of the hip after hip revision surgery often causes limping, pain, and instability of the implant. The purpose of our paper is to describe a mesh technique to repair hip abductor mechanism injuries after hip revision. PATIENTS AND METHODS: Forty-six patients with hip abductor damage after prosthetic revision were treated. Inclusion criteria were: patients presenting with prosthetic loosening, complaint of pain, and with a positive Trendelenburg sign due to deficient abductor muscle mechanisms. Thirty-one were women (67.39%) with an average age of 64 years (34-82 years). The number of previous revision surgeries was three (two to seven). The Merle d'Aubigne score and variants before and after treatment were also reported. RESULTS: In the postoperative follow-up after hip revision with the mesh technique, the Merle d'Aubigne score improved and the Trendelenburg sign was negative in 78.3% of the patients (p < 0.001). Also, the Trendelenburg test with the knee flexed was negative in 60.9% (p < 0.001) and the stair-climbing test was negative in 60.9% of cases (p < 0.001). The gluteus medius test in the lateral position was negative in 52.2% of patients, and in the lateral position with the knee flexed it was negative in 47.8% of patients (p < 0.001). DISCUSSION: Repair of the abductor mechanism with the mesh technique has proven effective for both partial and total lesions. PMID- 27382926 TI - Acute Resistance Exercise Facilitates Attention Control in Adult Males without an Age-Moderating Effect. AB - The current study examined the effects of acute resistance exercise (RE) on adult males' attention control. Eighteen younger males (23.9 +/- 2.3 years) and 17 older males (66.4 +/- 1.2 years) were recruited. Participants underwent a RE session and a reading session in a counterbalanced order. RE protocol required individuals to perform two sets of 10 repetitions of eight exercises using weights set at 70% of 10-repetition maximum. Attention control was assessed by go/no-go SART with intraindividual variability in reaction times (IIV in RT), in addition to reaction time and accuracy, employed as measures of attention control. Results indicated that IIV in RT was smaller following RE sessions than after reading sessions for both age groups. In addition, RTs were shorter after the exercise session. These findings suggest that RE enhances attention control in adult males and that the size of this effect is not moderated by age. PMID- 27382928 TI - Double Layer of a Gold Electrode Probed by AFM Force Measurements. AB - Colloidal probe atomic force microscopy was used to determine the electric double layer interactions between a gold electrode and a spherical silica probe. The double layer properties of the gold/solution interface were varied through the pH and salt concentration of the electrolyte, as well as by externally applying an electric potential. The double layer potentials psi(d) of the gold surface were obtained by fitting the force-distance curves according to the DLVO (Derjaguin Landau-Verwey-Overbeek) theory, using earlier obtained values for the double layer potential of the silica probe as input parameter. It was found that the gold electrode combines the features of reversible and polarizable interfaces; i.e., its charge and potential are determined by both the solution pH and the external potential. The pH dependence is attributed to proton adsorption and desorption from oxidic groups on the gold surface. In the potential range studied, psi(d) varies linearly with the applied potential; the variation in psi(d) is roughly 10% of that in the applied potential. The potential of zero force (the external potential at which psi(d) = 0) varies with pH. The various features of the gold/electrolyte interface are described well by an amphifunctional double layer model. The results of this study form the basis of the interpretation of adsorption studies on gold as a function of pH and externally applied potential. PMID- 27382927 TI - Raman Spectroscopic Characterization of Melanoma and Benign Melanocytic Lesions Suspected of Melanoma Using High-Wavenumber Raman Spectroscopy. AB - Melanoma is a pigmented type of skin cancer, which has the highest mortality of all skin cancers. Because of the low clinical diagnostic accuracy for melanoma, an objective tool is needed to assist clinical assessment of skin lesions that are suspected of (early) melanoma. The aim of this study was to identify spectral differences in the CH region of HWVN (high-wavenumber) Raman spectra between melanoma and benign melanocytic lesions clinically suspected of melanoma. We used these spectral differences to explore preliminary classification models to distinguish melanoma from benign melanocytic lesions. Data from 82 freshly excised melanocytic lesions clinically suspected of melanoma were measured using an in-house built Raman spectrometer, which has been optimized for measurements on pigmented skin lesions (excitation wavelength 976 nm and a wavelength range of the Raman signal 1340-1540 nm). Clear spectral differences were observed between melanoma and benign melanocytic lesions. These differences can be assigned mainly to the symmetric CH2 stretching vibrations of lipids. Our results show that the Raman bands between 2840 and 2930 cm(-1) have increased intensity for melanoma when compared to benign melanocytic lesions, suggesting an increase in lipid content in melanoma. These results demonstrate that spectroscopic information in the CH-stretching region of HWVN Raman spectra can discriminate melanoma from benign melanocytic lesions that are often clinically misdiagnosed as melanoma and that Raman spectroscopy has the potential to provide an objective clinical tool to improve the clinical diagnostic accuracy of skin lesions suspected of melanoma. PMID- 27382929 TI - Structural and magnetic characterization of large area, free-standing thin films of magnetic ion intercalated dichalcogenides Mn0.25TaS2 and Fe0.25TaS2. AB - Free-standing thin films of magnetic ion intercalated transition metal dichalcogenides are produced using ultramicrotoming techniques. Films of thicknesses ranging from 30 nm to 250 nm were achieved and characterized using transmission electron diffraction and x-ray magnetic circular dichroism. Diffraction measurements visualize the long range crystallographic ordering of the intercalated ions, while the dichroism measurements directly assess the orbital contributions to the total magnetic moment. We thus verify the unquenched orbital moment in Fe0.25TaS2 and measure the fully quenched orbital contribution in Mn0.25TaS2. Such films can be used in a wide variety of ultrafast x-ray and electron techniques that benefit from transmission geometries, and allow measurements of ultrafast structural, electronic, and magnetization dynamics in space and time. PMID- 27382930 TI - [Development of a Conceptual Framework for the Assessment of Chronic Care in the Spanish National Health System]. AB - The aim was to develop a conceptual framework for the assessment of new healthcare initiatives on chronic diseases within the Spanish National Health System. A comprehensive literature review between 2002 and 2013, including systematic reviews, meta-analysis, and reports with evaluation frameworks and/or assessment of initiatives was carried out; integrated care initiatives established in Catalonia were studied and described; and semistructured interviews with key stakeholders were performed. The scope and conceptual framework were defined by using the brainstorming approach.Of 910 abstracts identified, a total of 116 studies were included. They referred to several conceptual frameworks and/or assessment indicators at a national and international level. An overall of 24 established chronic care initiatives were identified (9 integrated care initiatives); 10 in-depth interviews were carried out. The proposed conceptual framework envisages: 1)the target population according to complexity levels; 2)an evaluation approach of the structure, processes, and outcomes considering the health status achieved, the recovery process and the maintenance of health; and 3)the dimensions or attributes to be assessed. The proposed conceptual framework will be helpful has been useful to develop indicators and implement them with a community-based and result-oriented approach and a territorial or population-based perspective within the Spanish Health System. This will be essential to know which are the most effective strategies, what are the key elements that determine greater success and what are the groups of patients who can most benefit. PMID- 27382931 TI - Novel therapeutic options for cachexia and sarcopenia. AB - INTRODUCTION: Cachexia and sarcopenia are conditions phenotypically characterized by muscle loss and represent a factor of poor prognosis, increasing patients' morbidity and mortality. Cachectic and sarcopenic patients often suffer from low quality of life, presenting lower muscle strength and appetite loss, which makes research on novel treatment strategies to ameliorate clinical response including patient's symptoms, the objective of scientific interest. AREAS COVERED: This article covers recent developments in the area of cachexia and sarcopenia treatment and therapeutic interventions, targeting central nervous system involvement, key inflammatory and muscle-specific metabolic pathways. EXPERT OPINION: A number of promising agents have being evaluated, such as enobosarm, a selected androgen receptor modulator, and anamorelin, a ghrelin agonist which have been recently studied in phase III trials. These and other agents (i.e., infliximab, tocilizumab, MABp1, bimagrumab) have shown significant impact on reversal of skeletal muscle loss, but limited effect on physical function. In the last few years advancement in the number and type of potential treatments for cachexia and sarcopenia have been obtained and we have now available more data on measurable effects of several drugs on patients' nutritional and metabolic parameters and outcomes. PMID- 27382932 TI - Replacing the Orchestra? - The Discernibility of Sample Library and Live Orchestra Sounds. AB - Recently, musical sounds from pre-recorded orchestra sample libraries (OSL) have become indispensable in music production for the stage or popular charts. Surprisingly, it is unknown whether human listeners can identify sounds as stemming from real orchestras or OSLs. Thus, an internet-based experiment was conducted to investigate whether a classic orchestral work, produced with sounds from a state-of-the-art OSL, could be reliably discerned from a live orchestra recording of the piece. It could be shown that the entire sample of listeners (N = 602) on average identified the correct sound source at 72.5%. This rate slightly exceeded Alan Turing's well-known upper threshold of 70% for a convincing, simulated performance. However, while sound experts tended to correctly identify the sound source, participants with lower listening expertise, who resembled the majority of music consumers, only achieved 68.6%. As non-expert listeners in the experiment were virtually unable to tell the real-life and OSL sounds apart, it is assumed that OSLs will become more common in music production for economic reasons. PMID- 27382933 TI - Evolution equation for quantum coherence. AB - The estimation of the decoherence process of an open quantum system is of both theoretical significance and experimental appealing. Practically, the decoherence can be easily estimated if the coherence evolution satisfies some simple relations. We introduce a framework for studying evolution equation of coherence. Based on this framework, we prove a simple factorization relation (FR) for the l1 norm of coherence, and identified the sets of quantum channels for which this FR holds. By using this FR, we further determine condition on the transformation matrix of the quantum channel which can support permanently freezing of the l1 norm of coherence. We finally reveal the universality of this FR by showing that it holds for many other related coherence and quantum correlation measures. PMID- 27382934 TI - The efficacy of intravenous hyoscine-N-butylbromide during colonoscopy: a prospective, randomized, double-blind, placebo-controlled study. AB - BACKGROUND: Colonic spasm makes colonoscope advancement difficult. This prospective, randomized, double-blind, placebo-controlled study aimed to evaluate the efficacy of hyoscine-N-butylbromide as an antispasmodic during colonoscopy. METHOD: Patients referred for elective colonoscopy were randomized into the study and placebo groups. Before the procedure, the study and placebo groups received 20 mg intra-venous hyoscine-N-butylbromide and intravenous saline solution of the same amount, respectively. Demographic and procedure--related data were recorded and compared between the groups. RESULTS: Of 198 patients referred for elective colonoscopy, 121 were included (study group = 60, placebo group = 61). No differences were observed between the study and placebo groups in terms of demographic data, pre-procedure characteristics, and colonoscopic characteristics including the cecal intubation time, total procedure time, bowel preparation, sedation doses, hemo-dynamic findings, endoscopist satisfaction, patient comfort, and polyp detection rate. The only difference was an increase in the heart rate by 32% in the study group after hyoscine-N-butyl-bromide administration (p < 0.001). CONCLUSIONS: Hyoscine-N-butylbromide did not reduce the time to reach the cecum and the total colonoscopy time, and patient and endoscopist satisfaction and polyp detection rate did not change. Furthermore, it was concluded that hyoscine-N-butylbromide can increase the risk of drug-related complications. PMID- 27382935 TI - Usefulness of IT knife nano for endoscopic submucosal dissection of large colo rectal lesions. AB - AIM: Endoscopic submucosal dissection (ESD) is currently widely conducted for the treatment of early gastrointestinal -cancers. Due to the characteristic anatomy of the large intestine, needle- tip type devices such as Dual knife are mainly used in colorectal ESD. On the other hand, the non- needle-tip type IT knife is a unique device with an insulated tip, and has been reported to be safe, efficacious and speedy when used in gastric ESD. A new model of IT knife, IT knife nano, anticipated to be useful for esophageal and colorectal ESD has become available, but its usefulness has not been reported. Therefore, we performed this study to evaluate the usefulness of IT knife nano for ESD of large colorectal lesions. METHOD: Previous studies have shown that a tumor size of 40 mm or above significantly prolongs treatment time and is a factor of treatment difficulty. We selected colorectal lesions of 40 mm and above, and compared 32 lesions treated with Dual knife alone before IT knife nano was available (No-IT group) and 40 cases treated with IT knife nano as a second knife after IT knife nano became available (IT group). We assessed en bloc resection rate, complete en bloc resection rate, complication rate and treatment time. RESULTS: The en bloc resection rates in No-IT group and IT group were 100% and 97.5%, respectively, with no significant difference. The respective median treatment time was 70 min and 51 min, and was significantly shortened in IT group (P < 0.05). The respective rates of procedure- related perforation were 3.1% and 0% ; in IT group suggesting a tendency of reduced incidence. CONCLUSIONS: Use of IT knife nano in ESD for large colorectal -lesions achieves the same levels of efficacy and safety as conventional device, with the additional merit of shortening treatment time. PMID- 27382936 TI - Fragmented QRS is associated with cirrhotic cardiomyopathy in patients with decompensated cirrhosis. AB - BACKGROUND AND AIM: It has been reported that the fragmented QRS (fQRS) is related to left ventricular systolic dysfunction and diastolic dysfunction. The aim of this study was to determine the frequency of fragmented QRS (fQRS) in patients with decompensated cirrhosis and to evaluate the relationship between the presence of fQRS and systolic and diastolic dysfunction. METHOD: PThe study included consecutive 189 patients with decompensated cirrhosis. fQRS pattern was described as presence of RSR' manifested as existence of additional R wave and notching in either R or S waves in ECG recordings. Conventional echocardiography and tissue doppler echocardiography were performed in all patients. RESULTS: The prevalence of fQRS was 31% (59/189) in patients with decompensated cirrhosis. The patients with fQRS had worse diastolic and systolic functions in comparison to the patients without fQRS. In addition, multivariate analysis revealed that the presence of an fQRS, Na levels < 125 mEq/L, the Child-Pugh score and the MELD score were independent predictive factors for mortality (respectively, p < 0.001, p < 0.001, p < 0.001 and p < 0.001). CONCLUSIONS: In conclusion,this study showed a relationship between the presence of an fQRS and cardiac dysfunction. In addition, the fQRS appeared to act as an independent predictor of mortality in patients with decompensated cirrhosis. These data suggest that the fQRS may represent a novel noninvasive marker for cardiac involvement and for predicting mortality in patients with decompensated cirrhosis. PMID- 27382937 TI - CDX2 as a prognostic marker in gastric cancer. AB - BACKGROUND: There is considerable evidence in the literature to suggest a role for CDX2 in intestinal metaplasia and development of gastric cancer, but its impact on the prognosis of gastric cancer continues to be a matter of debate. OBJECTIVE: We conducted this study to assess the prognostic -implications of CDX2 in gastric cancer. METHOD: We retrospectively reviewed our database for gastric carcinoma cases diagnosed at our hospital from 2004 to 2008. Histopathology slides of these were subsequently stained with CDX2 immuno-histochemical stain. CDX2 positive and negative groups were then compared for overall survival. RESULTS: A total of 101 patients (mean age 50y ; 60% male) were included in the study. 31/101 (30.7%) cases were CDX2 positive. Of these, 23/31 (74%) patients underwent curative surgical resection. In the CDX2 negative group, only 12/70 (17%) patients underwent curative surgery (p = .0001). Of those who underwent surgical resection, 9% had stage I, 37% had stage II, 43% had stage III, and 11% had stage IV tumours on TNM staging of post-surgical histological specimens. Mean overall survival of CDX2 positive group was 17 months, compared to 6 months in the CDX2 negative group (p = 0.0001). CONCLUSIONS: CDX2 positive gastric carcinomas are more likely to be resectable and patients whose tumours stain positive for CDX2 have significantly better survival. PMID- 27382938 TI - Anemia Outcome After Laparascopic Mini Bypass : Analysis of 107 Consecutive Patients. AB - BACKGROUND: The prevalence of obesity has dramatically increased globally. Weight loss procedures are known to be an effective and reliable method with relatively low complication rate and satisfactory results. Laparoscopic mini-gastric bypass (LMGB) is known as a modified Mason loop procedure with compatible results to laparoscopic Roux-en-Y gastric bypass (LRYGB), and is believed to have even less complication rate. Despite adequate and meticulous supplement therapy, anemia is one of the challenges in patients undergoing LMGB. Thus, we aimed to review the prevalence and severity of anemia in patients undergoing LMGB. METHOD: A prospectively-maintained database of patients referring to Hazrat Rasoul Akram hospital who underwent LMGB from December 2013 to October 2014 was reviewed retrospectively. RESULTS: A total of 113 consecutive patients were included in the study. The mean age was 38.7 +/- 9.8 years. Mean Body mass index (BMI) was 45.5 +/- 6.1 kg/m2 preoperatively and 36.7 +/- 5.5 kg/m2 and 33.0 +/- 5.3 kg/m2 three and six months after the procedure, respectively. (P = 0.001) Mean excess body weight loss after the procedure was 20% and 53% at three and six months post operatively. Serum hemoglobin (Hb) level decreased significantly in three months (P = 0.036) and remained unchanged in six months compared to 3-month (P = 0.385). Vitamin B12 level increased significantly in three months (P = 0.010) and then decrease in six months to the preoperative level (P = 0.889). CONCLUSION: LMGB is a safe, feasible and an effective alternative weight loss procedure. Simply, anemia can be prevented by utilizing therapeutic dose of multivitamin in patients who underwent this procedure. PMID- 27382939 TI - Polymorphisms in the IL28B gene (rs12979860, rs8099917) and the virological response to pegylated interferon therapy in hepatitis D virus patients. AB - AIM: Few data are available regarding the effects of interleukin 28B (IL28B) polymorphisms in chronic hepatitis D (CHD) patients. This study investigated the relationship between IL28B poly-morphisms and the response of patients with CHD infections to pegylated interferon (PEG-IFN) therapy. MATERIALS AND METHODS: A total of 101 CHD patients were -selected, 80 of whom (46 males ; median age 41 years) satisfied the inclusion criteria and were enrolled in the study. Thirty seven patients were treated with peg-IFNalpha for at least 12 months and were followed for a median of 18 months (range, 12-30 months). The primary treatment endpoint was the suppression of HDV replication, as documented by the loss of detectable HDV RNA in serum. Genotyping was used to analyse the IL28B polymorphisms rs12979860 and rs8099917 according to the virological response. RESULTS: After treatment, a sustained viral response (SVR) was achieved in 19 (51%) of the patients treated with PEG-INF. The IL28B genotypes in the 80 patients were as follows : CC in 36 (45%), CT in 33 (41%) and TT in 11 (14%) for rs12979860, and GG in 4 (5%), GT in 27 (34%) and TT in 49 (61%) for rs8099917. SVR was achieved in 5 (26%), 10 (53%) and 4 (21%) patients with CC, CT and TT at rs12979860, respectively, and one (5%), nine (47%) and nine (47%) patients with GG, GT and TT at rs8099917, respectively. There were differences in the SVR among genotypes (rs12979860 and rs8099917 ; chi-squared test, p = 0.047). CONCLUSION: IL28B predicts the PEG-IFN response in patients with CHD infection. PMID- 27382940 TI - Post progression survival analysis of metastatic gastric and gastroesophageal junction cancer patients after second-line treatment. AB - PURPOSE: The aim of this study was to define the factors that -affect response and post-progression survival of metastatic gastric cancer (MGC) and gastroesophageal junction cancer (GEJ) -patients treated with second-line chemotherapy. METHODS: We retrospectively reviewed the data of 59 patients with MGC or GEJ adenocarcinoma who received second-line treatment. RESULTS: The median age was 54 years old (26-77). Response to second-line treatment was strongly associated with disease control with first-line treatment (p < 0.01). Median progression-free survival (PFS), overall survival (OS) and post-progression survival (PPS) were 3.2 (95% CI : 2.63-3.80), 6.5 (95% CI : 3.78-9.35) and 2.7 months (95% CI : 1.89-3.68), respectively. PFS (r = 0.55, p < 0.01) and PPS (r = 0.89, p < 0.01) were correlated with OS. Response to second-line treatment was independently related to PFS (HR : 0.12 95%CI : 0.53-0.26, p < 0.001). Having an ECOG 0 performance status (HR : 0.42 ; 95%CI : 0.21-0.86, p = 0.02) and response to second-line therapy (HR : 0.47 ; 95%CI : 0.25-0.85, p = 0.01) were independently associated with OS. CONCLUSION: PPS and PFS were correlated with OS after second-line treatment of MGC. Response to second-line treatment prolonged OS by increasing PFS, and having an ECOG 0 PS prolonged OS by increasing PPS. PMID- 27382941 TI - Comparing the type and severity of inflammatory bowel disease in relation to IgG4 immunohistochemical staining. AB - BACKGROUD AND STUDY AIM: The role of immunoglobulin (Ig) G4 in the etiopathogenesis of inflammatory bowel disease (IBD) and its association with endoscopic and pathological activity are not yet completely understood. The purpose of this study was to determine the possible relationship between IgG4 status and IBD. PATIENTS AND METHODS: Endoscopic colon biopsies of 55 patients with ulcerative colitis (UC) and of 17 patients with Crohn's disease (CD) were examined. Numbers of IgG4-positive plasma cells stained immunohistochemically were counted in a minimum of 5 high power fields (HPFs) for each specimen. The presence of > 10 cells/HPF IgG4-positive PCs was considered positive. RESULTS: he prevalence of IgG4-positive plasma cells in the lamina propria of the colonic mucosa was significantly higher in patients with UC than in those with CD (p :0.01). Additionally, the prevalence of IgG4-positive plasma cells increased in line with endoscopic and pathological activity in UC patients. Conversely, we determined no significant correlation between IgG4 positivity and pathological activity in the CD group. IgG4-positive UC patients also exhibited findings of more severe disease compared to IgG4-negative UC patients. CONCLUSION: Immunohistochemical IgG4 staining may predict disease severity in UC and may be a useful marker for distinguishing between UC and CD. PMID- 27382942 TI - Achieving WHO recommendations for Hepatitis C Virus Elimination in Belgium. AB - BACKGROUD: The World Health Organization (WHO) released updated guidelines for the screening, care and treatment of patients with chronic hepatitis C virus (HCV) infection. METHODS: A previously described HCV disease burden model was used to develop a "WHO scenario" to achieve the WHO recommendations of a 90% reduction in incidence and 65% reduction in liver-related deaths. After determining the steps necessary to achieve this goal, the impact of realistic constraints was modeled. RESULTS: In 2015, there were 66.200 viremic infections, with 43% diagnosed and 1.350 treated. In order to reduce new infections, treatment must be extended to >= F0 patients, including people who inject drugs and other individuals at risk of transmitting HCV. -Additionally, diagnosis and treatment of 3.030 and 4.060 patients, respectively, would be required. The largest attenuation of the WHO scenario would occur if no new cases were diagnosed after 2018 (300% more viremic infections by 2030). Limiting treatment to >= F2 patients or treating fewer patients (3.000) would result in 220% or 140% more viremic cases, respectively, compared with the WHO scenario. CONCLUSION: Achieving the WHO guidelines in Belgium requires a coordinated effort to scale up treatment and prevention efforts and to allow treatment access to patients of all fibrosis stages. A scale-up of treatment, however, requires patients to be both diagnosed and linked to care, suggesting a need for increased awareness and expanded screening efforts. Finally, prevention of new HCV infections requires a comprehensive understanding of the population at risk of transmitting HCV. PMID- 27382943 TI - Mitigating the burden of hepatitis C virus among people who inject drugs in Belgium. AB - BACKGROUD AND AIMS: In 2010, there were an estimated 10 100 PWID in Belgium and 43% (34%-57%) were HCV infected. Understanding HCV transmission dynamics in high risk populations and assessing the potential impact of improved HCV treatment strategies requires robust epidemiological data and mathematical modeling. METHODS: CV transmission was modeled using cohorts to track HCV incidence and prevalence among active PWID in the general PWID population, OST and NSP. Model assumptions were derived from published literature and expert consensus. The relative impact of increasing the number of PWID treated with new oral DAAs was considered. RESULTS: If the current transmission paradigm continues, there will be 2645 HCV-infected PWID in 2030. Annually treating 30 (1% of 2015 population) or 120 (4% of 2015 population) HCV-infected PWID with oral DAAs will result in 5% and 25% reductions, respectively, in HCV-infected PWID by 2030. Treating 370 PWID annually (12.5% of 2015 population) will result in a > 90% reduction by 2030. CONCLUSION: Treating a small number of PWID can result in substantial reduction in HCV prevalence in this population ; however, high levels of treatment are necessary to reduce the viral pool and thus the risk of secondary infections. This analysis supports implementation of a screening and treatment strategy among PWID when combined with an expansion of harm reduction programs. PMID- 27382944 TI - A review on the role of laparoscopy in pancreatic cancer. AB - BACKGROUD: Pancreatic cancer is the fourth leading cause of cancer death in the United States and leads to an estimated 227,000 deaths per year worldwide. Palliative and curative treatments are used for pancreatic cancer by laparoscopic or open techniques. The role of laparoscopy in pancreatic cancer is evaluated in this study. MATERIAL AND METHODS: Electronic databases, such as PubMed/MEDLINE and Google Scholar were searched to identify reports of trials for laparoscopic pancreatic surgery. Articles written in English including the maximum number of patients published -between 2010 and 2014 were included. RESULTS: Recent reports on laparoscopic surgery of the pancreas are encouraging and support the advantages of laparoscopy. Although large series have been reported for benign pancreatic -tumors treated with laparoscopic procedures, only limited data are available for malignant lesions. Most of these studies are retrospective, but the results encourage laparoscopic procedures. CONCLUSION: Over the last decade laparoscopic pancreatic surgery has emerged as an alternative to open surgery with many advantages. There are limited data on about laparoscopic approach for the treatment of malignant lesions. The results are in favor of laparoscopy. PMID- 27382945 TI - Eosinophilic Gastroenteritis : Brief Review. AB - Eosinophilic gastroenteritis (EGE) is a rare disease which belongs to primary eosinophilic gastrointestinal disorders (primary EGIDs), characterized by an accumulation of eosinophils in the gastrointestinal (GI) tract and is strongly associated with atopy and allergy. The clinical presentations vary depending on the site and depth of eosinophilic intestinal infiltration. Radiology pictures may show irregular thickening of the folds, but these findings can also be present in other conditions like inflammatory bowel disease and lymphoma. The endoscopic appearance is also nonspecific. The definite diagnosis requires biopsy for histological evidence of GI eosinophilic infiltration and clinicians make the diagnosis in correlation with and by exclusion of other possible causes of eosinophilic infiltration. Because EGE is a rare disease, the treatment is based on limited case reports and clinicians' experience. Corticosteroids are the mainstay of therapy. The prognosis of EGE is relatively good when patients receive timely and proper treatment. PMID- 27382946 TI - Eosinophilic esophagitis that develops during therapy with proton pump inhibitors : case series and possible mechanisms. AB - Therapy with proton-pump inhibitors (PPIs) results in remission in at least one third of patients with esophageal eosinophilia, presumably because of both their acid-related and anti-inflammatory mechanisms of action. However, eosinophilic esophagitis (EoE) may also develop during therapy with PPIs. We present a case series of four children who were initially diagnosed with infectious esophagitis, gastroesophageal reflux disease or gastric ulcer, who had no eosinophilic infiltration of the esophagus, but subsequently developed symptoms, endoscopic features and histological picture of typical EoE. We discuss mechanisms of action of PPIs of likely relevance to an increased risk of development of EoE in some patients, such as their influence on mucosal barrier function, interference with pH-related protein digestion by pepsin, and antigen processing by immune cells. PMID- 27382947 TI - Uncommon cause of retrosternal pain. AB - We present the case of a 54-year old male patient who was admitted with severe acute epigastric pain, vomiting, and inability to eat since three days before admission. After having excluded cardiac and pulmonary emergencies, an oesogastroduodenoscopy was planned and showed a gastric volvulus. The patient was treated surgically allowing gastric decompression, gastropexy and Nissen intervention. We discuss the case and describe the classification, the diagnosis, the etiologies and therapeutic options in acute and chronic gastric volvulus. PMID- 27382948 TI - Sclerosing mesenteric panniculitis in a young patient : common cause of diagnostic dilemma and treatment refractoriness. AB - BACKGROUND: Sclerosing mesenteric panniculitis (SMP) is an idiopathic chronic fibroinflammatory disorder of the intra-abdominal fat. CASE PRESENTATION: Herin, we report a case of SMP, involving the omentum, mesentery and peri-colic fat in a 18 year old male, who presented with significant and recurrent abdominal distension for 4.5 years. Computed tomogram revealed ascites, with nodular and irregular omental thickening and foci of calcification. Non-specific radiological and histological features made an accurate diagnosis extremely difficult. After a thorough work up and exclusion of other differentials, diagnosis of a nodular SMP (Weber Christian disease) was given. After showing resistance to chemotherapeutic agents, slow response was noted with cyclophosphamide, followed by rapid symptomatic improvement with mesenterectomy. CONCLUSION: SMP is an uncommon benign mesenteric/ omental inflammation, and is a diagnosis of exclusion. As treatment refractoriness is common, management should be individualized and continued for along period. Surgical omentectomy may be helpful. PMID- 27382949 TI - An unusual case of haemolytic uraemic syndrome following endoscopic retrograde cholangiopancreatography rapidly improved with eculizumab. AB - Atypical haemolytic uraemic syndrome (aHUS) is a rare but life-threatening complement system-related disorder, characterized by renal failure, non-immune haemolytic anaemia and thrombo-cytopenia. We report on a young woman who developed a pancreatitis-induced aHUS following a routine procedure of endoscopic retrograde cholangiopancreatography. The patient was successively treated by 2 plasma exchanges with fresh frozen plasma and eculizumab, a monoclonal antibody designed to block terminal complement activation. The last treatment resulted in the immediate improvement of haemolytic parameters and to the definitive suspension of plasma exchanges. This is likely the first description of the use of a complement inhibitor to treat post-pancreatitis aHUS. We discussed treatment options and concluded that eculizumab could be a beneficial alternative to plasma exchanges in the management of such complications. PMID- 27382950 TI - Case of a successful liver transplantation from a living donor with focal nodular hyperplasia. PMID- 27382951 TI - A rare case of abdominal tuberculosis with vomiting : letter to the editor. PMID- 27382952 TI - Abdominal pain and fullness in young patient. PMID- 27382953 TI - Fecal transplant for Clostridium difficile infection relapses using "pooled" frozen feces from non-related donors. PMID- 27382954 TI - Esophageal and gastric ulceration due to synchronous herpes simplex virus, cytomegalovirus and Epstein-Barr virus infection. PMID- 27382955 TI - Computed tomography findings of polysplenia syndrome with multiple anomalies. PMID- 27382956 TI - A rarely seen biliary variation : Right posterior and right anterior hepatic ducts were opening to the cystic duct. PMID- 27382957 TI - Brain-Derived Neurotrophic Factor in Children and Adolescents with Cirrhosis Due to Biliary Atresia. AB - BACKGROUND: The nutritional status in patients with cirrhosis is not so easy to assess properly. Considering the relationship between brain-derived neurotrophic factor (BDNF) and energy homeostasis, the main aim of this study was to evaluate the concentration of BDNF in children and adolescents with cirrhosis due to biliary atresia (BA) and correlate it with their nutritional status. METHODS: Fifty-three children and adolescents with cirrhosis due to BA and 33 healthy controls were enrolled in this study. Nutritional status was evaluated using anthropometric parameters, and serum BDNF was measured by ELISA. Spearman coefficient was used to evaluate the correlation between variables. RESULTS: In the cirrhosis group, 28.8% were undernourished and in the control group, 100% were well-nourished. BDNF median values for the control and cirrhosis group were 28.5 and 9.0 pg/ml respectively. BDNF and platelets were positively associated with both Standard Deviation Score (SDS) for height-for-age ratio and SDS for triceps skinfold thickness-for-age ratio. CONCLUSIONS: Considering these associations, BDNF may be an indirect biomarker of nutritional status in children and adolescents with chronic liver disease. Further studies must be conducted to clarify the role of BDNF in this population. PMID- 27382958 TI - Sensory quality of Camembert-type cheese: Relationship between starter cultures and ripening molds. AB - Starter cultures and ripening molds used in the manufacture of moldy cheese aimed at obtaining characteristic flavors and textures considerably differ among dairy industries. Thus, the study of variables inherent to the process and their influence on sensory patterns in cheese can improve the standardization and control of the production process. The aim of this work was to study the influence of three different variables on the sensory quality of Camembert-type cheese: type of lactic bacteria, type of ripener molds and inoculation method. Batches of Camembert-type cheese were produced using O or DL-type mesophilic starter culture, ripened with Penicillium camemberti or Penicillium candidum and mold inoculation was made directly into the milk or by spraying. All batches were sensorially evaluated using Quantitative Descriptive Analysis (QDA) with panelists trained for various attributes. Among the combinations analyzed, those resulting in more typical Camembert-type cheese were those using O-type mesophilic starter culture and P. candidum maturation mold directly applied into the milk or sprayed and those using DL-type mesophilic starter and P. camemberti ripener mold applied by surface spraying. These results demonstrate, therefore, that the combination of different ripener molds, inoculation methods and starter cultures directly influences the sensory quality of Camembert-type cheese, modifying significantly its texture, appearance, aroma and taste. PMID- 27382959 TI - Quantitative transfer of Salmonella Typhimurium LT2 during mechanical slicing of tomatoes as impacted by multiple processing variables. AB - Slicing of fresh produce can readily lead to pathogen cross-contamination with pre-sliced tomatoes having been linked to multistate outbreaks of salmonellosis in the United States. This study aimed to assess the impact of multiple processing variables on quantitative transfer of Salmonella during simulated commercial slicing of tomatoes. One red round tomato was inoculated with Salmonella Typhimurium LT2 at ~5logCFU/g and sliced using a manual or electric slicer, followed by 20 uninoculated tomatoes. Thereafter, the distribution of Salmonella on inoculated and uninoculated tomato slices was evaluated along with the transfer of Salmonella from different parts of the slicer. The impact of multiple processing variables including post-contamination hold time (0 and 30min), tomato wetness (dry and wet), processing room temperature (23, 10 and 4 degrees C), slice thickness (0.48, 0.64, and 0.95cm), tomato variety (Torero, Rebelski, and Bigdena) and pre-wash treatment (no wash, tap water, and chlorine) was also investigated. The data were fitted to a two-parameter exponential decay model (Y=A?exp(BX)) with the percentage of Salmonella transferred to 20 uninoculated tomatoes then calculated. Salmonella populations on nine inoculated tomato slices ranged from 4.6+/-0.2 to 5.5+/-0.3logCFU/g, with higher populations on slices from the blossom and stem scar ends. However, Salmonella transfer to the previously uninoculated slices was similar (P>0.05), ranging from 2.1+/-0.2 to 3.4+/-0.2logCFU/g. Significantly fewer salmonellae transferred from the blade (3.4+/-0.4 log CFU, P<=0.05) than from the back and bottom plates (4.7+/-0.3 log CFU) or the whole manual slicer (5.2+/-0.2 log CFU) to the 20 uninoculated tomatoes. However, the blade was the primary contributor to Salmonella transfer for the electric slicer. Post-contamination hold time, processing temperature and tomato slice thickness did not significantly impact (P>0.05) the Salmonella transfer rate (parameter B) or the overall percentage of cells transferred. A significantly lower (P<=0.05) transfer rate (-0.028+/-0.002) was observed for wet as compared to dry tomatoes (-0.051+/-0.002), with a significantly higher (P<=0.05) percentage (12.2+/-2.4%) of Salmonella transferred to wet as opposed to dry tomatoes (1.1+/-0.5%). Tomato variety also impacted Salmonella transfer with significantly lower (P<=0.05) transfer rates and Salmonella transfer percentages seen for Rebelski and Bigdena than Torero. These findings will provide practical guidelines for the fresh-cut tomato industry and will also be useful in developing science-based transfer models for risk assessments. PMID- 27382960 TI - A novel method for the determination of some pesticides in vegetable oils based on dissociation extraction followed by gas chromatography-mass spectrometry. AB - The distribution of 40 pesticides of basic nature in different extraction systems was studied at 20 +/- 1 degrees C. The distribution constants (P) and distribution ratios (D) between n-hexane and polar phases are calculated. It was found that the studied pesticides are most fully and selectively extracted from hexane and vegetable oils by solutions of perchloric acid in acetonitrile. In particular, the acidification of acetonitrile decreases the D-value of fenpropimorph by 29,000 times. This phenomenon was used for the development of an improved technique for the quantitative analysis of widely used pesticides of basic nature in rapeseed, linseed, sunflower and olive oils by GC-MS. The proposed approach allows obtaining much purer sample extracts, compared with the use of standard solvent extraction with further purification by the freezing-out technique. This approach expands the range of pesticides (flutriafol, fenpropidine, metazachlor, cyprodinil and others) that can be determined by GC MS. The recovery values of the studied pesticides from vegetable oils were between 85% and 115% with RSD values below 10%. The obtained limits of detection ranged from 0.001 to 0.1 mg kg(-)(1), and are below or equal to the maximum residue levels (MRLs) set by the European Union for the corresponding pesticides. PMID- 27382961 TI - Overexpression of SORCIN is a Prognostic Biomarker for Multidrug-Resistant Pediatric Acute Lymphoblastic Leukemia and Correlates with Upregulated MDR1/P-gp. AB - BACKGROUND: Multidrug resistance is one of the major causes of treatment failure in pediatric acute lymphoblastic leukemia (ALL), and SORCIN is an intracellular calcium modulator protein. The current study was designed to investigate the in vitro and in vivo relationships between the expression levels of SORCIN: in tumor cell lines and children with ALL; its possible correlation with MDR1/P glycoprotein (P-gp), a multidrug resistance-related gene; and response to therapy. MATERIALS AND METHODS: Childhood T-lymphoblastic leukemia (CCRF-CEM) cell lines resistant to methotrexate (MTX) were developed. Patient studies were performed by including 30 children with ALL at diagnosis, 3 children with bone marrow relapse, and 15 children with no symptoms of cancer. The mRNA expression profiles of SORCIN and MDR1/P-gp was assessed using quantitative polymerase chain reaction (qPCR). Minimal residual disease (MRD) was measured in the patient population, a year following the initial therapy using qPCR. RESULTS: Cell line data analyses showed a positive correlation between SORCIN mRNA levels and resistance to MTX. The difference between patient and control groups for SORCIN expression levels was not significant. However, patients with a negative response to therapy showed an increase in SORCIN mRNA levels (up to 6.8-fold) compared with those with negative MRD. In addition, the results demonstrated a significant positive correlation between SORCIN and MDR1/P-gp gene expression levels. CONCLUSION: The current study introduces, for the first time, a possible prognostic value of SORCIN in childhood ALL, which may be correlated with MDR1/P gp gene expression in these patients. PMID- 27382963 TI - Clinical Scores for Dyspnoea Severity in Children: A Prospective Validation Study. AB - BACKGROUND: In acute dyspnoeic children, assessment of dyspnoea severity and treatment response is frequently based on clinical dyspnoea scores. Our study aim was to validate five commonly used paediatric dyspnoea scores. METHODS: Fifty children aged 0-8 years with acute dyspnoea were clinically assessed before and after bronchodilator treatment, a subset of 27 children were videotaped and assessed twice by nine observers. The observers scored clinical signs necessary to calculate the Asthma Score (AS), Asthma Severity Score (ASS), Clinical Asthma Evaluation Score 2 (CAES-2), Pediatric Respiratory Assessment Measure (PRAM) and respiratory rate, accessory muscle use, decreased breath sounds (RAD). RESULTS: A total of 1120 observations were used to assess fourteen measurement properties within domains of validity, reliability and utility. All five dyspnoea scores showed overall poor results, scoring insufficiently on more than half of the quality criteria for measurement properties. The AS and PRAM were the most valid with good values on six and moderate values on three properties. Poor results were mainly due to insufficient measurement properties in the validity and reliability domains whereas utility properties were moderate to good in all scores. CONCLUSION: This study shows that commonly used dyspnoea scores show insufficient validity and reliability to allow for clinical use without caution. PMID- 27382962 TI - Crystal Structure of Bacillus subtilis Cysteine Desulfurase SufS and Its Dynamic Interaction with Frataxin and Scaffold Protein SufU. AB - The biosynthesis of iron sulfur (Fe-S) clusters in Bacillus subtilis is mediated by a SUF-type gene cluster, consisting of the cysteine desulfurase SufS, the scaffold protein SufU, and the putative chaperone complex SufB/SufC/SufD. Here, we present the high-resolution crystal structure of the SufS homodimer in its product-bound state (i.e., in complex with pyrodoxal-5'-phosphate, alanine, Cys361-persulfide). By performing hydrogen/deuterium exchange (H/DX) experiments, we characterized the interaction of SufS with SufU and demonstrate that SufU induces an opening of the active site pocket of SufS. Recent data indicate that frataxin could be involved in Fe-S cluster biosynthesis by facilitating iron incorporation. H/DX experiments show that frataxin indeed interacts with the SufS/SufU complex at the active site. Our findings deepen the current understanding of Fe-S cluster biosynthesis, a complex yet essential process, in the model organism B. subtilis. PMID- 27382965 TI - Comments on Isoflavones in Soy-Based Infant Formulas. PMID- 27382964 TI - Dependence of Initial Value on Pattern Formation for a Logistic Coupled Map Lattice. AB - The logistic coupled map lattices (LCML) have been widely investigated as well as their pattern dynamics. The patterns formation may depend on not only fluctuations of system parameters, but variation of the initial conditions. However, the mathematical discussion is quite few for the effect of initial values so far. The present paper is concerned with the pattern formation for a two-dimensional Logistic coupled map lattice, where any initial value can be linear expressed by corresponding eigenvectors, and patterns formation can be determined by selecting the corresponding eigenvectors. A set of simulations are conducted whose results demonstrate the fact. The method utilized in the present paper could be applied to other discrete systems as well. PMID- 27382967 TI - Adding to the transitional care evidence base for future national guidance. PMID- 27382968 TI - The Primary Prevention of PTSD in Firefighters: Preliminary Results of an RCT with 12-Month Follow-Up. AB - AIM: To develop and evaluate an evidence-based and theory driven program for the primary prevention of Post-traumatic Stress Disorder (PTSD). DESIGN: A pre intervention / post-intervention / follow up control group design with clustered random allocation of participants to groups was used. The "control" group received "Training as Usual" (TAU). METHOD: Participants were 45 career recruits within the recruit school at the Department of Fire and Emergency Services (DFES) in Western Australia. The intervention group received a four-hour resilience training intervention (Mental Agility and Psychological Strength training) as part of their recruit training school curriculum. Data was collected at baseline and at 6- and 12-months post intervention. RESULTS: We found no evidence that the intervention was effective in the primary prevention of mental health issues, nor did we find any significant impact of MAPS training on social support or coping strategies. A significant difference across conditions in trauma knowledge is indicative of some impact of the MAPS program. CONCLUSION: While the key hypotheses were not supported, this study is the first randomised control trial investigating the primary prevention of PTSD. Practical barriers around the implementation of this program, including constraints within the recruit school, may inform the design and implementation of similar programs in the future. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12615001362583. PMID- 27382969 TI - A sensitive multi-residue method for the determination of 35 micropollutants including pharmaceuticals, iodinated contrast media and pesticides in water. AB - A sensitive, multi-residue method using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed to determine a representative group of 35 analytes, including corrosion inhibitors, pesticides and pharmaceuticals such as analgesic and anti-inflammatory drugs, five iodinated contrast media, beta-blockers and some of their metabolites and transformation products in water samples. Few other methods are capable of determining such a broad range of contrast media together with other analytes. We studied the parameters affecting the extraction of the target analytes, including sorbent selection and extraction conditions, their chromatographic separation (mobile phase composition and column) and detection conditions using two ionisation sources: electrospray ionisation (ESI) and atmospheric pressure chemical ionisation (APCI). In order to correct matrix effects, a total of 20 surrogate/internal standards were used. ESI was found to have better sensitivity than APCI. Recoveries ranging from 79 to 134 % for tap water and 66 to 144 % for surface water were obtained. Intra-day precision, calculated as relative standard deviation, was below 34 % for tap water and below 21 % for surface water, groundwater and effluent wastewater. Method quantification limits (MQL) were in the low ng L(-1) range, except for the contrast agents iomeprol, amidotrizoic acid and iohexol (22, 25.5 and 17.9 ng L(-1), respectively). Finally, the method was applied to the analysis of 56 real water samples as part of the validation procedure. All of the compounds were detected in at least some of the water samples analysed. Graphical Abstract Multi-residue method for the determination of micropollutants including pharmaceuticals, iodinated contrast media and pesticides in waters by LC-MS/MS. PMID- 27382970 TI - The influence of ageing and surface type on the odour profile of blood-detection dog training aids. AB - Cadaver-detection dogs are a preferred search tool utilised by law enforcement agencies for the purposes of locating victim remains due to their efficiency and minimal disturbance to the crime scene. In Australia, a specific group of these canines are blood-detection dogs, which are trained to detect and locate blood evidence and search potential crime scenes in cases where a cadaver may not be present. Their role sometimes requires searches to be carried out after considerable time has passed since the crime occurred, and this is important for developing effective training protocols. This study aimed to investigate the volatile organic compounds (VOCs) produced from fresh and aged human blood on various surfaces. Solid phase microextraction (SPME) was used to extract VOCs from the headspace of dried blood samples aged and sampled periodically over 12 months from a non-porous (i.e. aluminium) and porous (i.e. cotton) surface. Samples were analysed using comprehensive two-dimensional gas chromatography-time of-flight mass spectrometry (GC*GC-TOFMS). Fresh blood produced distinctively different VOC patterns compared to blood aged longer than 1 week with the overall profile differing between the two surface types, and a large subset of the VOC profile found to be responsible for these differences. When analysing the various functional groups present in the samples, a common pattern between ages and surface types was observed with no specific chemical class dominating the overall profile. The results highlight the importance of evaluating training aids for scent-detection canines to ensure the greatest efficacy during training and subsequently at crime scene searches. PMID- 27382972 TI - [Not Available]. PMID- 27382973 TI - [Not Available]. PMID- 27382971 TI - Black phosphorus-assisted laser desorption ionization mass spectrometry for the determination of low-molecular-weight compounds in biofluids. AB - Quantitative analysis of small molecules by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been a challenging task due to matrix-derived interferences in low m/z region and poor reproducibility of MS signal response. In this study, we developed an approach by applying black phosphorus (BP) as a matrix-assisted laser desorption ionization (MALDI) matrix for the quantitative analysis of small molecules for the first time. Black phosphorus-assisted laser desorption/ionization mass spectrometry (BP/ALDI-MS) showed clear background and exhibited superior detection sensitivity toward quaternary ammonium compounds compared to carbon-based materials. By combining stable isotope labeling (SIL) strategy with BP/ALDI-MS (SIL-BP/ALDI MS), a variety of analytes labeled with quaternary ammonium group were sensitively detected. Moreover, the isotope-labeled forms of analytes also served as internal standards, which broadened the analyte coverage of BP/ALDI-MS and improved the reproducibility of MS signals. Based on these advantages, a reliable method for quantitative analysis of aldehydes from complex biological samples (saliva, urine, and serum) was successfully established. Good linearities were obtained for five aldehydes in the range of 0.1-20.0 MUM with correlation coefficients (R (2)) larger than 0.9928. The LODs were found to be 20 to 100 nM. Reproducibility of the method was obtained with intra-day and inter-day relative standard deviations (RSDs) less than 10.4 %, and the recoveries in saliva samples ranged from 91.4 to 117.1 %. Taken together, the proposed SIL-BP/ALDI-MS strategy has proved to be a reliable tool for quantitative analysis of aldehydes from complex samples. Graphical Abstract An approach for the determination of small molecules was developed by using black phosphorus (BP) as a matrix-assisted laser desorption ionization (MALDI) matrix. PMID- 27382974 TI - Solid-Phase Purification of Synthetic DNA Sequences. AB - Although high-throughput methods for solid-phase synthesis of DNA sequences are currently available for synthetic biology applications and technologies for large scale production of nucleic acid-based drugs have been exploited for various therapeutic indications, little has been done to develop high-throughput procedures for the purification of synthetic nucleic acid sequences. An efficient process for purification of phosphorothioate and native DNA sequences is described herein. This process consists of functionalizing commercial aminopropylated silica gel with aminooxyalkyl functions to enable capture of DNA sequences carrying a 5'-siloxyl ether linker with a "keto" function through an oximation reaction. Deoxyribonucleoside phosphoramidites functionalized with the 5'-siloxyl ether linker were prepared in yields of 75-83% and incorporated last into the solid-phase assembly of DNA sequences. Capture of nucleobase- and phosphate-deprotected DNA sequences released from the synthesis support is demonstrated to proceed near quantitatively. After shorter than full-length DNA sequences were washed from the capture support, the purified DNA sequences were released from this support upon treatment with tetra-n-butylammonium fluoride in dry DMSO. The purity of released DNA sequences exceeds 98%. The scalability and high-throughput features of the purification process are demonstrated without sacrificing purity of the DNA sequences. PMID- 27382975 TI - Imidazoline scaffold in medicinal chemistry: a patent review (2012-2015). AB - INTRODUCTION: Until very recently, the 'imidazoline drugs' were perceived as a class of central and/or peripheral sympatholytics and vasodilators acting at either the imidazoline binding sites and/or alpha-adrenergic receptors. However, in recent years it has become evident that the imidazoline scaffold is also contained in synthetic agents that exhibit a broad spectrum of biological activities. AREAS COVERED: This review provides an insight into the patents filed in the years 2012-2015, and considers 2-imidazoline-containing compounds with proven biological properties. Special attention is paid to agents for which practical applications as active ingredients of pharmaceutical compositions, diagnostic imaging agents, insecticides and herbicides, may be found. EXPERT OPINION: 2-Substituted imidazolines can exist in multiple tautomeric forms. The implication is that imidazolines and their imidazolidine tautomers cannot be regarded as isofunctional structures and the term 'imidazoline scaffold' should be treated with caution. Nevertheless, for medicinal chemists the progress made in development of both the imidazoline- and imidazolidine-containing agents useful for the treatment of neurodegenerative, inflammatory, autoimmune, cancer, and infectious diseases is of the utmost importance. PMID- 27382976 TI - Cytotoxicity of withasteroids: withametelin induces cell cycle arrest at G2/M phase and mitochondria-mediated apoptosis in non-small cell lung cancer A549 cells. AB - Considerable interest has been gained by withasteroids because of their structural uniqueness and wide spectrum of biological activities. However, limited systematic studies for proving their cytotoxic potential have so far been reported. Hence, an attempt was made to test the cytotoxicity of six withasteroids viz., withametelin (WM), withaphysalin D, withaphysalin E, 12 deoxywithastramonolide, Withaperuvin B, and physalolactone against A549, HT-29, and MDA-MB-231 cancer cell lines. Significant cytotoxic effect of WM against A549 cells (IC50 value of 6.0 MUM), MDA-MB-231 cells (IC50 value of 7.6 MUM), and HT 29 cells (IC50 value of 8.2 MUM) was observed. Withaperuvin B and physalolactone were found to be effective against MDA-MB-231 cells. The significantly active WM arrested the A549 cells at G2/M phase and downregulated the expression of G2/M regulatory proteins such as cdc2, cyclin B1, and cdc25C. Apoptosis induced by WM in A549 cells was associated with the generation of ROS and depletion of MMP. Furthermore, WM treatment resulted in Bax upregulation, Bcl-2 downregulation, translocation of cytochrome c to mitochondria, activation of caspase-9 and -3, and PARP cleavage corroborating the apoptosis induction through intrinsic apoptotic pathway. Thus, WM possessing broader cytotoxic effect is a promising lead molecule which has the potential to be developed as a new therapeutic agent for NSCLC. PMID- 27382977 TI - THE CAUSAL RELATIONSHIP BETWEEN CONSANGUINEOUS MARRIAGES AND INFANT MORTALITY IN TURKEY. AB - Turkey has high levels of infant mortality and consanguineous marriages. It has had a high level of infant mortality for its economic level for many years. Over recent decades, although adult mortality rates have not been very different from those of other countries with similar socioeconomic structures, its life expectancy at birth has remained low due to its high infant mortality rate. This has been called the Turkish Puzzle. According to the Turkey Family Structure and Population Issues Survey, 27% of women had a consanguineous marriage in 1968. Subsequent Turkish Demographic and Health Surveys (TDHSs) found the rate of consanguineous marriages to be stagnated at 22-24%, with a resistance to reduction. According to the TDHS-2008, 24% of women had a consanguineous marriage. Numerous studies in various countries of the world have indicated that consanguineous marriages, particularly of first-degree, have the effect of increasing infant mortality. The main aim of this study was to assess the causal impact of consanguineous, particularly first-degree consanguineous, marriages on infant mortality, controlling for individual, cultural, bio-demographic and environmental factors. Data were merged from four Turkish DHS data sets (1993, 1998, 2003 and 2008). Multivariate analysis revealed that first-degree consanguineous marriages have increased infant mortality by 45% in Turkey: 57% in urban areas and 39% in rural areas. The results indicate that there is a causal relationship between consanguineous marriages and infant mortality. This finding should be taken into account when planning policies to reduce infant mortality in Turkey, and in other countries with high rates of consanguineous marriage and infant mortality. PMID- 27382978 TI - Atrial fibrillation after lung cancer surgery: incidence, severity, and risk factors. AB - PURPOSE: Atrial fibrillation (Af) is a common post-operative cardiac complication after lung cancer surgery; however, the type of lung cancer surgery being performed has evolved, remarkably, into minimally invasive surgical procedures. The purpose of this study was to quantify the incidence and severity of post operative Af and to identify the risk factors for Af, using a recent cohort of lung cancer surgery patients. METHODS: We reviewed, retrospectively, the medical records of 593 patients, who underwent lung cancer surgery between 2011 and 2013, for the development of post-operative Af. RESULTS: The overall incidence of post operative Af in our study was 6.4 % (38/593). Three (8 %) of these 38 patients, subsequently, suffered brain infarction. Multivariate analysis revealed that mediastinal lymph node dissection (OR ND-2/ND-0-1 = 3.06; 95 % CI 1.06-10.9) was associated with the development of post-operative Af. CONCLUSION: Omission of mediastinal lymph dissection for patients with early stage lung cancer and a high risk of Af should be considered to prevent post-operative Af. PMID- 27382979 TI - The GG genotype of the -152 G/A vascular endothelial growth factor (VEGF) polymorphism predisposes to hypertension-related chronic kidney disease. AB - Our purpose was to determine whether the VEGF -152 G/A polymorphism could be associated with chronic kidney disease and endothelial dysfunction in hypertensive patients. There were 100 healthy volunteers enrolled into the control group. The group of patients was constituted by 99 consecutively admitted hypertensive patients referred to our Institution by their general practitioner. All patients were treated with anti-hypertensive polytherapy. Presented study revealed that the hypertensive patients bearing the GG genotype were characterized by the highest values of diastolic blood pressure and markers of endothelial damage such as Angiogenin, Endostatin, CRP as well as von Willebrandt factor. In addition, higher number of immature endothelial progenitor cells with CD34(+)CD133(+), CD34(+)CD133(-) markers was observed in GG hypertensive carriers while in normotensive individuals no differences were found. Such phenomenon may indicate an increased mobilization of bone-marrow derived endothelial progenitors. It may testify to the preserved compensatory mechanism in chronic kidney disease (CKD) patients until the G3a stage of the disease. Moreover, patients with higher estimated glomerular filtration rate (eGFR) level had lower of vWf and Endostatin values, and higher level of VEGF. Taken together our findings clearly indicate the -152 GG hypertensive carriers as more prone to develop CKD. We can suspect that the VEGF -152 GG genotype is strongly associated with hypertension-dependent CKD. PMID- 27382980 TI - Effect of photoperiod on development and demographic parameters of Neoseiulus barkeri (Acari: Phytoseiidae) fed on Tyrophagus putrescentiae (Acari: Acaridae). AB - Effects of five photoperiods (Light:Dark = 4:20, 8:16; 12:12, 16:8, 20:4) on the development, survival and reproduction of Neoseiulus barkeri Hughes fed on storage mite Tyrophagus putrescentiae (Schrank) were examined under laboratory conditions at 85 % relative humidity and 24 degrees C. Development time of almost all immature stages in N. barkeri was the shortest (5.43 +/- 0.12 days) under 12 h of daylight. Total duration of immature stages was as high as 8.55 +/- 0.16 days during the longest photoperiod. Photoperiod had no effect on hatching rate, but did affect survival of larvae, protonymphs and deutonymphs. Total survivorship ranged from 20 (4:20) to 60 % (12:12). Under 12 h daylight, female adults had the shortest pre- and post-oviposition period, longest oviposition period and longevity, largest total number of eggs (15.95) and and highest daily egg production (1.43) per female. Under 12 h light, N. barkeri experienced its highest net reproductive rate (R 0 = 11.791), intrinsic rate of increase (r m = 0.180), and finite rate of increase (lambda = 1.197), and lowest mean generation time (t = 13.71 days) and population doubling time (DT = 3.86 days). All demographic parameters displayed a parabolic relationship with photoperiod. The results of the present study indicated that the photoperiod of 12:12 is optimal for the development and reproduction of N. barkeri fed on T. putrescentiae, and that N. barkeri may serve most efficiently as a biological control agent under this regime. PMID- 27382981 TI - Diversity and distribution of tick species (Acari: Ixodidae) associated with human otoacariasis and socio-ecological risk factors of tick infestations in Sri Lanka. AB - Tick infestation in humans is a major public health concern. The diversity and distribution of tick species associated with human otoacariasis was studied in five districts: Anuradhapura, Kandy, Kurunegala, Nuwara Eliya and Ratnapura in the main agro-climatic zones of Sri Lanka. Ticks from patients attending the ear, nose and throat clinics of the General Hospitals were collected during a 3 year period. In total 426 ticks were collected. Most human otoacariasis cases were reported from Kandy (33.8 %) and the fewest from Nuwara Eliya (8.2 %). Of the five tick species identified, nymphs of Dermacentor auratus constituted 90.6 % of the collection. Rhipicephalus sanguineus, Hyalomma isaaci, Haemaphysalis bispinosa and Otobius megnini were found rarely infesting humans possibly as an accidental host; H. bispinosa and O. megnini in the human ear canal were first time records in Sri Lanka. Females and children under 10 years were identified as risk groups of human otoacariasis. Subsequently, a field study was carried out to determine socio-ecological risk factors of human tick infestations in the five districts. Based on hospital data, eight villages with high prevalence of otoacariasis were selected from each district. A total 40 villages were visited and 1674 household members were interviewed. Involvement in outdoor activities, presence of wild animals around the house, location of the house in close proximity to a forest and occupation were identified as major risk factors. PMID- 27382983 TI - Nursery policies on conjunctivitis may encourage GPs to prescribe antibiotics. PMID- 27382984 TI - Phenotypic familial aggregation in chronic chilblains. AB - BACKGROUND: Our clinical observations and two earlier studies indicate familial clustering to be involved in chronic chilblains. Demonstrating phenotypic familial aggregation is a next step to investigate the origin of familial clustering. OBJECTIVE: This study was initiated to assess evidence for phenotypic familial aggregation in chronic chilblains. METHODS: Using a case-control family design in a primary care setting, we computed the familial relative risk of at least one episode of chronic chilblains during life with 95% confidence intervals (CIs). The study population consisted of 192 relatives of 31 case probands (at least one confirmed episode of chronic chilblains). The control population consisted of 178 relatives of 31 sex- and age-matched index controls (no history of chronic chilblains). RESULTS: The familial relative risk of chronic chilblains was 3.6 (95% CI 1.9-7.3). Additional sensitivity analysis shows similar figures. CONCLUSION: We demonstrate robust phenotypic familial aggregation in chronic chilblains. PMID- 27382982 TI - Epigenetic Modifications and Therapy in Multiple Sclerosis. AB - Breakthroughs in genetic studies, like whole human genome sequencing and genome wide association studies (GWAS), have richened our knowledge of etiopathology of autoimmune diseases (AID) through discovery of genetic patterns. Nonetheless, the precise etiology of autoimmune diseases remains largely unknown. The lack of complete concordance of autoimmune disease in identical twins suggests that non genetic factors also play a major role in determining disease susceptibility. Although there is no certain definition, epigenetics has been known as heritable alterations in gene function without changes in the nucleotide sequence. DNA methylation, histone modifications, and microRNA-associated gene expression suppression are the central mechanisms for epigenetic regulations. Multiple sclerosis (MS) is a disorder of the central nervous system (CNS), characterized by both inflammatory and neurodegenerative features. Although studies on epigenetic alterations in MS only began in the past decade, a mounting number of surveys suggest that epigenetic changes may be involved in the initiation and development of MS, probably through bridging the effects of environmental risk factors to genetics. Arming with clear understanding of epigenetic dysregulations underpins development of epigenetic therapies. Identifying agents inhibiting the enzymes controlling epigenetic modifications, particularly DNA methyltransferases and histone deacetylases, will be promising therapeutic tool toward MS. In the article underway, it is aimed to go through the recent progresses, attempting to disclose how epigenetics associates with the pathogenesis of MS and how can be used as therapeutic approach. PMID- 27382985 TI - Immunosuppression in idiopathic membranous nephropathy: A double-edge sword. PMID- 27382986 TI - Impairment of autophagy by TTR V30M aggregates: in vivo reversal by TUDCA and curcumin. AB - Transthyretin (TTR)-related amyloidoses are diseases characterized by extracellular deposition of amyloid fibrils and aggregates in tissues composed of insoluble misfolded TTR that becomes toxic. Previous studies have demonstrated the ability of small compounds in preventing and reversing TTR V30M deposition in transgenic mice gastrointestinal (GI) tract as well as lowering biomarkers associated with cellular stress and apoptotic mechanisms. In the present study we aimed to study TTR V30M aggregates effect in autophagy, a cellular mechanism crucial for cell survival that has been implicated in the development of several neurodegenerative diseases. We were able to demonstrate in cell culture that TTR V30M aggregates cause a partial impairment of the autophagic machinery as shown by p62 accumulation, whereas early steps of the autophagic flux remain unaffected as shown by autophagosome number evaluation and LC3 turnover assay. Our studies performed in TTR V30M transgenic animals demonstrated that tauroursodeoxycholic acid (TUDCA) and curcumin effectively reverse p62 accumulation in the GI tract pointing to the ability of both compounds to modulate autophagy additionally to mitigate apoptosis. Overall, our in vitro and in vivo studies establish an association between TTR V30M aggregates and autophagy impairment and suggest the use of autophagy modulators as an additional and alternative therapeutic approach for the treatment of TTR V30M-related amyloidosis. PMID- 27382988 TI - Selective synthesis of large diameter, highly conductive and high density single walled carbon nanotubes by a thiophene-assisted chemical vapor deposition method on transparent substrates. AB - Selective synthesis of single-walled carbon nanotubes (SWNTs) with controlled properties is an important research topic for SWNT studies. Here we report a thiophene-assisted chemical vapor deposition (CVD) method to directly grow highly conductive SWNT thin films on substrates, including transparent ones. By adding low concentration thiophene into the carbon feedstock (ethanol), the as-prepared carbon nanotubes demonstrate an obvious up-shift in the diameter distribution while the single-walled structure is still retained. In the proposed mechanism, the change in the diameter is sourced from the increase in the carbon yield induced by the sulfur-containing compound. Such SWNTs are found to possess high conductivity with 95% SWNTs demonstrating on/off ratios lower than 100 in transistors. More importantly, it is further demonstrated that this method can be used to directly synthesize dense SWNT networks on transparent substrates which can be utilized as transparent conductive films (TCFs) with very high transparency. Such TCFs can be applied to fabricate a light modulating window as a proof-of-concept. The present work provides important insights into the growth mechanism of SWNTs and great potential for the preparation of TCFs with high scalability, easy operation and low cost. PMID- 27382989 TI - Further evidence of VRK2 rs2312147 associated with schizophrenia. AB - OBJECTIVES: Previous genome-wide association studies (GWAS) have reported that rs2312147 near the VRK2 gene was significantly associated with schizophrenia in populations of European descent, but negative results have also been observed. METHODS: To perform a systematic meta-analysis, we collected statistical data of rs2312147 from both GWAS and individual replication samples in European and Asian populations, which finally included up to 30,867 schizophrenia patients and 59,863 healthy controls. RESULTS: The VRK2 rs2312147 was genome-wide significantly associated with schizophrenia in combined populations (P = 1.31 * 10(-15), odds ratio, OR = 1.10) as well as in Europeans only (P = 2.35 * 10(-12), OR =1.09). In Asian samples, the SNP did not reach genome-wide level of statistical significance (P = 1.23 * 10 (-) (5), OR =1.19), which is likely due to the limited power of small sample size in this population (2,974 cases and 4,786 controls). However, the effect size of rs2312147 did not alter significantly between populations, and is also in agreement with the observed effect sizes of other genetic risk loci in large scale studies. CONCLUSIONS: Our data provides further evidence for the genetic contributions of VRK2 rs2312147 to schizophrenia susceptibility especially in Europeans, while further replication analyses in Asian populations are still needed, and future studies, e.g., the underlying molecular mechanisms of genetic risk, are necessary. PMID- 27382987 TI - Increase of Total Nephron Albumin Filtration and Reabsorption in Diabetic Nephropathy. AB - The amount of albumin filtered through the glomeruli and reabsorbed at the proximal tubules in normal and in diabetic kidneys is debated. The megalin/cubilin complex mediates protein reabsorption, but genetic knockout of megalin is perinatally lethal. To overcome current technical problems, we generated a drug-inducible megalin-knockout mouse line, megalin(lox/lox);Ndrg1 CreERT2 (iMegKO), in which megalin expression can be shut off at any time by administration of tamoxifen (Tam). Tam administration in adult iMegKO mice decreased the expression of renal megalin protein by 92% compared with that in wild-type C57BL/6J mice and almost completely abrogated renal reabsorption of intravenously injected retinol-binding protein. Furthermore, urinary albumin excretion increased to 175 MUg/d (0.46 mg albumin/mg creatinine) in Tam-treated iMegKO mice, suggesting that this was the amount of total nephron albumin filtration. By comparing Tam-treated, streptozotocin-induced diabetic iMegKO mice with Tam-treated nondiabetic iMegKO mice, we estimated that the development of diabetes led to a 1.9-fold increase in total nephron albumin filtration, a 1.8 fold increase in reabsorption, and a significant reduction in reabsorption efficiency (86% efficiency versus 96% efficiency in nondiabetic mice). Insulin treatment normalized these abnormalities. Akita;iMegKO mice, another model of type 1 diabetes, showed equivalent results. Finally, nondiabetic iMegKO mice had a glomerular sieving coefficient of albumin of 1.7*10-5, which approximately doubled in diabetic iMegKO mice. This study reveals actual values and changes of albumin filtration and reabsorption in early diabetic nephropathy in mice, bringing new insights to our understanding of renal albumin dynamics associated with the hyperfiltration status of diabetic nephropathy. PMID- 27382990 TI - Valence matters: Positive meta-stereotypes and interethnic interactions. AB - Two experimental studies were conducted that aimed at testing whether the activation of positive meta-stereotypes among high-status group members involved in conflictual relationships with the low-status group is beneficial for intergroup relations. Results revealed that the activation of positive meta stereotypes led Italian high-school students (high-status group) to anticipate greater enjoyment of an upcoming interaction with an African immigrant (low status group) by increasing positive feelings about contact and concerns about being accepted. Initial prejudice emerged as the moderator, with the effects of positive meta-stereotypes present among those with average- to high-levels of prejudice. This study represents the first experimental demonstration that positive meta-stereotypes have beneficial effects for intergroup relations among high-status members. The theoretical and practical implications of the findings are discussed. PMID- 27382991 TI - Ant assemblage (Hymenoptera: Formicidae) in three wind farms in the State of Parana, Brazil. AB - The transformation of natural habitats into areas destined to agriculture or projects of energy production has generated a growing concern about the impact on biological diversity. Thus, this study evaluated the diversity of ants in agroecosystems in the area of direct influence of three wind farms in the municipality of Marmeleiro, State of Parana and examined the association of occurrences with sampling periods. To this end, four samplings were conducted in 2013, one per season. Pitfalls, Malaise trap and Net sweep were used. The assemblages were characterized and compared using richness and number of occurrences of ants. Chao 2 estimates were calculated and a comparison (rarefaction analysis) of the assemblages was performed. The association of the species with the samples was evaluated by a Principal Component Analysis (PCA). Altogether, there were 1,576 occurrences of ants, totaling 55 species. The obtained estimate indicated that richness may be up to 35% higher. Our study adds important information about richness and occurrence of ants in a region poorly analyzed for this group. Most of all, it presents a survey of species occurring in agricultural ecosystems that may serve as a parameter for future evaluations when wind farms are installed. PMID- 27382992 TI - Neolasioptera pantaneira, a new species of Cecidomyiidae (Diptera) associated with Aeschynomene denticulata (Fabaceae) from Brazil. AB - A new species of gall midge that induces stem galls on Aeschynomene denticulata (Fabaceae) is described based on material collected in Pantanal (Mato Grosso do Sul, Brazil). This species is unique among the Brazilian congeners in having spatula with three convex teeth, cruciate, with defined anterolateral extensions, four lateral papillae on each side of the spatula, and three pairs of terminal papillae (larva), four-segmented palpi (adult), 17 flagellomeres (female), ovipositor about 11 times length of seventh tergite. PMID- 27382993 TI - Biological properties of disturbed and undisturbed Cerrado sensu stricto from Northeast Brazil. AB - The aim of this study was to measure soil microbial biomass and soil surface fauna in undisturbed and disturbed Cerrado sensu stricto (Css) from Sete Cidades National Park, Northeast Brazil. The following sites were sampled under Cerrado sensu stricto (Css) at the park: undisturbed and disturbed Css (slash-and-burn agricultural practices). Total organic and microbial biomass C were higher in undisturbed than in disturbed sites in both seasons. However, microbial biomass C was higher in the wet than in the dry season. Soil respiration did not vary among sites but was higher in the wet than in the dry season. The densities of Araneae, Coleoptera, and Orthoptera were higher in the undisturbed site, whereas the densities of Formicidae were higher in the disturbed site. Non-metric multidimensional scaling analysis separated undisturbed from disturbed sites according to soil biological properties. Disturbance by agricultural practices, such as slash-and-burn, probably resulted in the deterioration of the biological properties of soil under native Cerrado sensu stricto in the Sete Cidades National Park. PMID- 27382994 TI - Occurrence of the Afro-Asian species Mesocyclops ogunnus Onabamiro, 1957 (Crustacea: Copepoda) in the Amazon River basin. PMID- 27382995 TI - Anatomical traits related to stress in high density populations of Typha angustifolia L. (Typhaceae). AB - Some macrophytes species show a high growth potential, colonizing large areas on aquatic environments. Cattail (Typha angustifolia L.) uncontrolled growth causes several problems to human activities and local biodiversity, but this also may lead to competition and further problems for this species itself. Thus, the objective of this study was to investigate anatomical modifications on T. angustifolia plants from different population densities, once it can help to understand its biology. Roots and leaves were collected from natural populations growing under high and low densities. These plant materials were fixed and submitted to usual plant microtechnique procedures. Slides were observed and photographed under light microscopy and images were analyzed in the UTHSCSA Imagetool software. The experimental design was completely randomized with two treatments and ten replicates, data were submitted to one-way ANOVA and Scott Knott test at p<0.05. Leaves from low density populations showed higher stomatal density and index. These modifications on stomatal characteristics were more evident on the leaf abaxial surface. Plants from low density populations showed thicker mesophyll and higher proportion of aerenchymal area. Roots from low density populations showed a higher proportion of the vascular cylinder. Whereas, plants from higher density populations showed greater thickness of the endodermis, exodermis, phloem and root cortex. Higher density populations showed a higher proportion of aerenchymal gaps in the root cortex. Therefore, cattail plants from populations growing under high density population show anatomical traits typical of plants under stress, which promotes the development of less functional anatomical modifications to aquatic environments. PMID- 27382996 TI - Beetle diversity in fragmented thornscrub and isolated trees. AB - Due to land use change mainly for induced agriculture, Tamaulipan thornscrubin northeast Mexico has been cleared and transformed into small patches of vegetation as small as isolated trees surrounded by agricultural fields. In this study, we explored how tree isolation or growing inside a fragment of remnant vegetation influence diversity of coleopterans in two plant species (Prosopis laevigata (Humb. &Bonpl.exWilld.) M.C. Johnst. (mesquite) and Ebenopsis ebano (Berl.) Barneby (Texas ebony). We found 72 coleopteran morphospecies; fifteen occurred mainly in remnant fragments and ten mainly in isolated trees. There were more insects under isolated mesquites than under those immersed in remnant fragments, while in Texas ebony the highest beetle density for isolated trees coincided with periods of bean and maize in surrounding agriculture. PMID- 27382997 TI - Evaluation of skeletal muscle regeneration in experimental model after malnutrition. AB - The aim of this study was to analyze muscle regeneration after cryoinjury in the tibialis anterior muscle of young rats that were malnourished and then recovered. Forty Wistar rats were divided into a nourished group that received a normal protein diet (14% casein) for 90 days and a malnourished and recovered rats group (MR) that was submitted to 45 days of malnutrition with a hypoproteic diet (6% casein) followed by 45 days of a normal protein diet (14% casein). After the recovery period, all of the animals underwent cryoinjury in the right tibialis anterior muscle and euthanasia after 7, 14 and 21 days. The amount of connective tissue and the inflammation area was higher in the malnutrition recovered injury MR group (MRI) at 14 days post-injury (p < 0.05). Additionally, the cross sectional area (CSA) of the regenerated fibers was decreased in the MRI (p < 0.05). The MyoD and myogenin protein levels were higher in the nourished injury group. Similar levels of TGF-beta1 were found between groups. The proposed malnutrition protocol was effective in showing delayed changes in the regeneration process of the tibialis anterior muscle of young rats. Furthermore, we observed a delay in muscle repair even after nutritional recovery. PMID- 27382998 TI - Toxicity of clove essential oil and its ester eugenyl acetate against Artemia salina. AB - The production of compounds via enzymatic esterification has great scientific and technological interest due to the several inconveniences related to acid catalysis, mainly by these systems do not fit to the concept of "green chemistry". Besides, natural products as clove oil present compounds with excellent biological potential. Bioactives compounds are often toxic at high doses. The evaluation of lethality in a less complex animal organism can be used to a monitoring simple and rapid, helping the identification of compounds with potential insecticide activity against larvae of insect vector of diseases. In this sense, the toxicity against Artemia salina of clove essential oil and its derivative eugenyl acetate obtained by enzymatic esterification using Novozym 435 as biocatalyst was evaluated. The conversion of eugenyl acetate synthesis was 95.6%. The results about the evaluation of toxicity against the microcrustacean Artemia salina demonstrated that both oil (LC50= 0.5993 ug.mL-1) and ester (LC50= 0.1178 ug.mL-1) presented high toxic potential, being the eugenyl acetate almost 5 times more toxic than clove essential oil. The results reported here shows the potential of employing clove oil and eugenyl acetate in insecticide formulations. PMID- 27382999 TI - Intra-specific pelage color variation in a South American small rodent species. AB - Intra-specific color variation is often underestimated by researchers, and among mammals, intra-specific differences in coloration are poorly documented for most species. The main goal of this study was to apply an objective color measurement methodology to the study of a specific problem: the detection, if any, of patterns of changes in the fur color of specimens of Akodon budini in relation to biological (i.e., sex) and environmental (i.e., season) variables. We hypothesize that coat color will be more homogeneous in males than in females and that coat color will be darker in winter than in summer, the latter being orange. We measured the pelage color on five points over the dorsal surface of 26 A. budini museum specimens using a spectroradiometer and a diffuse illumination cabin. We used Principal Component Analysis to describe the association between the color variables, sex and season, and each of the observations. We then used general linear models of Analysis of Variance to examine relationships between color data, season, and sex. The results clearly confirm the hypothesis related to seasonal coat color change but do not directly confirm the hypothesis related to changes in coat color in relation to sex, and we show the complexity of the studied pattern. In conclusion, undoubtedly, the studied variables should accordingly be considered when studying the coloration of specimens for characterization, identification and discrimination of different taxonomic units based on color. PMID- 27383000 TI - Mosquitoes (Diptera: Culicidae) from crepuscular period in an Atlantic Forest area in Southern Brazil. AB - Crepuscular period is one of the factors that may influence the biting activity of mosquitoes. Many of these insects have a peak activity in this period. The purpose of this study was to investigate the afternoon crepuscular activity of Culicidae in a remaining area of Atlantic Forest in western Santa Catarina, southern Brazil. Moreover, the possible influence of abiotic factors, the abundance and species richness were verified. In order to better analyze the influence of crepuscular period in specific composition and abundance of mosquitoes, the dusk was divided into three periods: pre-sunset, sunset and post sunset. At the end of the study, nine hundred and eight four specimens distributed in 12 genera and 23 species were collected. Trichoprosopon pallidiventer (Lutz, 1905) (59.76%), Aedes crinifer (Theobald, 1903) (8.13%), Ae. scapularis (Rondani, 1848) (5.89%) were the most abundant species. Spring time presented the greatest abundance and species richness. During the study, among the three periods evaluated, pre-sunset had the greatest abundance and post sunset the lowest. Pre-sunset and sunset had the greatest similarity between species. Regarding to the abiotic factors evaluated seven and 15 days before sampling, they did not present significant correlation for the three most abundant species. However, temperature had a positive correlation to these species. Moreover, the correlation between collected species and its possible role as vectors of etiological agents of diseases was discussed. PMID- 27383001 TI - Assessing the spatial pattern of a river water quality in southern Brazil by multivariate analysis of biological and chemical indicators. AB - This study assessed the genotoxicity and chemical quality of the Rio dos Sinos, southern Brazil. During two years, bimonthly, cuttings of Tradescantia pallida var. purpurea with flower buds were exposed to river water samples from Caraa, Santo Antonio da Patrulha, Taquara and Campo Bom, which are municipalities located in the upper, middle and lower stretches of the Rio dos Sinos basin. Simultaneously, chemical parameters were analyzed, rainfall data were surveyed and negative (distilled water) and positive (0.1% formaldehyde) controls were made. Micronuclei (MCN) frequencies were determined in tetrads of pollen grain mother cells. From the upper stretch toward the lower, there was an increase in the frequency of MCN and in concentrations of chemical parameters. Cadmium, lead, copper, total chromium and zinc were present at the four sites and a concentration gradient was not demonstrated along the river. The multivariate analysis revealed that two principal components exist, which accounted for 62.3% of the observed variances. Although genotoxicity was observed in Santo Antonio da Patrulha, the water presented higher mean values for most of the assessed parameters, in the lower stretch, where urbanization and industrialization are greater. The spatial and temporal pattern of water quality observed reinforces the importance of considering the environmental factors and their effects on organisms in an integrated way in watercourse monitoring programs. PMID- 27383002 TI - Isolation of entomopathogenic nematodes in an apple orchard in Southern Brazil and its virulence to Anastrepha fraterculus (Diptera: Tephritidae) larvae, under laboratory conditions. AB - Entomopathogenic nematodes (EPNs) are a promising alternative to integrated control in many fruit pests. Few studies were made on the relationship of Anastrepha fraterculus natural population with native EPNs population and other biotic and abiotic factors. The aim of this work was to verify the occurrence of endemic nematodes in an apple orchard, concerning environmental conditions and technical procedure, and access isolates virulence to A. fraterculus larvae. The experiment was conducted during a year taking monthly soil samples from an apple orchard, with and without fallen fruits just above the soil. Samples were baited with Tenebrium molitor and A. fraterculus larvae in laboratory. Canopy and fallen fruits were sampled to access the pest infestation. Seventy three EPN isolates were captured, in 23.2% soil samples, more with T. molitor than with A. fraterculus baits. From the 20 isolates tested against A. fraterculus, only five were pathogenic, and they were identified as Oscheius sp. The nematodes were captured during all seasons in a similar frequency. Soil and weather conditions, presence of fruit over the orchard soil, and A. fraterculus pupae in the fruits had no significant influence on the capture. As a conclusion, nematodes of the genera Oscheius are found in an apple orchard of Porto Amazonas constantly along the year, independently of fluctuations in A. fraterculus population, climate conditions and presence of fruit over the soil. Some of the isolates are pathogenic to A. fraterculus. PMID- 27383003 TI - Nematodes (Mermithidae) parasitizing grasshoppers (Orthoptera: Acrididae) in the Pampean region, Argentina. AB - This work provides the results of a survey of entomonematodes parasites of grasshoppers in grasslands of the Pampean Region, Argentina. Nymphs of Staurorhectus longicornis Giglio-Tos, Laplatacris dispar Rhen, 1939, Dichroplus elongatus Giglio-Tos, 1894 and Metaleptea brevicornis (L.) (Orthoptera: Acrididae) were collected. Mermithidae was the only family registered with seven species: Agamermis decaudata Cobb, Steiner and Christie, 1923, Amphimermis bonaerensis Miralles and Camino, 1983, Amphimermis dichroplusi Camino and Lange, 1997, Amphimermis ronderosi Camino and Lange, 1997, Hexamermis coclhearius Stock and Camino, 1992, Hexamermis ovistriata Stock and Camino, 1992, and Longimermis acridophila Camino and Stock, 1989. The values of parasitism ranged between 1 12%, and intensity not overcome the number of 5.0 nematodes per larva. The nematodes observed showed specificity, not registering the same species of parasite in more than one host species. The Pampean region constituted an area with high diversity of mermithids where new species could be consider as bioregulator agents of this troublesome insect pests in agricultural areas of Argentina. PMID- 27383004 TI - Analgesic prescribing in care home residents: how epidemiological studies may inform clinical practice. AB - Care home residents are often frail with multiple comorbidities and cognitive impairment, most commonly caused by dementia. This population is under represented in clinical trials, leading to a lack of valid and reliable evidence to inform clinicians' prescribing practice. This paper summarizes how epidemiological research conducted in similar populations can inform pain management by describing pain prevalence, risk factors, typical features and functional consequences. This evidence can help overcome the numerous barriers to optimal pain management in care home residents. PMID- 27383005 TI - Point contact resistive switching memory based on self-formed interface of Al/ITO. AB - Point contact resistive switching random access memory (RRAM) has been achieved by directly sputtering Al electrodes on indium tin oxide (ITO) conductive glasses. The room-temperature deposited Al/ITO shows an asymmetrical bipolar resistive switching (BRS) behavior after a process of initialization which induces a stable high resistive state (HRS). It might be caused by the in-situ formation of an ultra-thin layer (~4 nm) at the interface. By comparison, the Al/ITO device after vacuum annealed exhibits typical symmetrical BRS without an initiation or electroforming process. This can be ascribed to the ex-situ thickening of the interfacial layer (~9.2 nm) to achieve the stable HRS after heat treatment. This work suggests that the self-formed interface of active Al electrode/ITO would provide the simplest geometry to construct RRAM. PMID- 27383006 TI - Highly solvatochromic and tunable fluorophores based on a 4,5-quinolimide scaffold: novel CDK5 probes. AB - Novel 4,5-quinolimide-based fluorophores are more solvatochromic and red-shifted than known naphthalimide analogues. Conjugation of one of these fluorophores to a peptide derived from CDK5 kinase demonstrated its sensitivity for monitoring the interaction with its regulatory partner p25. Introduction of the quinolimide labelled peptide into living glioblastoma cells probed the interaction with endogenous p25. PMID- 27383009 TI - Windmill Co4 {Co4 (MU4 -O)} with 16 Divergent Branches Forming a Family of Metal Organic Frameworks: Organic Metrics Control Topology, Gas Sorption, and Magnetism. AB - A series of highly connected metal-organic frameworks (MOFs), [Co8 (O)(OH)4 (H2 O)4 (ina)8 ](NO3 )2 ?2 C2 H5 OH?4 H2 O (1), [Co8 (O)(OH)4 (H2 O)4 (pba)8 ](NO3 )2 ?8 C2 H5 OH?28 H2 O (2), and [Co8 (O)(OH)4 (H2 O)4 (pbba)8 ](NO3 )2 ?guest (3), in which ina=isonicotinate, pba=4-pyridylbenzoate, and pbba=4-(pyridine-4 yl)phenylbenzoate, is reported. These MOFs contain a new secondary building unit (SBU), with a square Co4 (MU4 -O) central unit having the rare MU4 -O(2-) motif, which is decorated by the other four peripheral cobalt atoms through MU3 -OH in a windmill-like shape. This SBU holds 16 divergent connecting organic ligands, pyridyl-carboxylates, to form three different frameworks. The high porosity of desolvated 2 is shown by the efficient gas absorption of N2 , CO2 , CH4 , and H2 . In addition, 1 and 2 exhibit unusual canted antiferromagnetic behavior with spin-glass-like relaxation, with blocking temperatures that are fairly high, 20 K (1) and 10 K (2), for cobalt materials. The relationship between the metal clusters and linkers has been studied, in which the size and rotational degrees of freedom of the ligands are found to control the topology, gas sorption, and magnetic properties. PMID- 27383008 TI - Eating 'Junk-Food' Produces Rapid and Long-Lasting Increases in NAc CP-AMPA Receptors: Implications for Enhanced Cue-Induced Motivation and Food Addiction. AB - Urges to eat are influenced by stimuli in the environment that are associated with food (food cues). Obese people are more sensitive to food cues, reporting stronger craving and consuming larger portions after food cue exposure. The nucleus accumbens (NAc) mediates cue-triggered motivational responses, and activations in the NAc triggered by food cues are stronger in people who are susceptible to obesity. This has led to the idea that alterations in NAc function similar to those underlying drug addiction may contribute to obesity, particularly in obesity-susceptible individuals. Motivational responses are mediated in part by NAc AMPA receptor (AMPAR) transmission, and recent work shows that cue-triggered motivation is enhanced in obesity-susceptible rats after 'junk food' diet consumption. Therefore, here we determined whether NAc AMPAR expression and function is increased by 'junk-food' diet consumption in obesity susceptible vs -resistant populations using both outbred and selectively bred models of susceptibility. In addition, cocaine-induced locomotor activity was used as a general 'read out' of mesolimbic function after 'junk-food' consumption. We found a sensitized locomotor response to cocaine in rats that gained weight on a 'junk-food' diet, consistent with greater responsivity of mesolimbic circuits in obesity-susceptible groups. In addition, eating 'junk food' increased NAc calcium-permeable-AMPAR (CP-AMPAR) function only in obesity susceptible rats. This increase occurred rapidly, persisted for weeks after 'junk food' consumption ceased, and preceded the development of obesity. These data are considered in light of enhanced cue-triggered motivation and striatal function in obesity-susceptible rats and the role of NAc CP-AMPARs in enhanced motivation and addiction. PMID- 27383010 TI - The Learning Curve in Laparoscopic Major Hepatectomy: What Is the Magic Number? PMID- 27383012 TI - Game of Zones: how actin-binding proteins organize muscle contraction. AB - Locomotion of C. elegans requires coordinated, efficient transmission of forces generated on the molecular scale by myosin and actin filaments in myocytes to dense bodies and the hypodermis and cuticle enveloping body wall muscles. The complex organization of the acto-myosin scaffold with its accessory proteins provides a fine-tuned machinery regulated by effectors that guarantees that sarcomere units undergo controlled, reversible cycles of contraction and relaxation. Actin filaments in sarcomeres dynamically undergo polymerization and depolymerization. In a recent study, the actin-binding protein DBN-1, the C. elegans ortholog of human drebrin and drebrin-like proteins, was discovered to stabilize actin in muscle cells. DBN-1 reversibly changes location between actin filaments and myosin-rich regions during muscle contraction. Mutations in DBN-1 result in mislocalization of other actin-binding proteins. Here we discuss implications of this finding for the regulation of sarcomere actin stability and the organization of other actin-binding proteins. PMID- 27383011 TI - S1PR2 variants associated with auditory function in humans and endocochlear potential decline in mouse. AB - Progressive hearing loss is very common in the population but we still know little about the underlying pathology. A new spontaneous mouse mutation (stonedeaf, stdf ) leading to recessive, early-onset progressive hearing loss was detected and exome sequencing revealed a Thr289Arg substitution in Sphingosine-1 Phosphate Receptor-2 (S1pr2). Mutants aged 2 weeks had normal hearing sensitivity, but at 4 weeks most showed variable degrees of hearing impairment, which became severe or profound in all mutants by 14 weeks. Endocochlear potential (EP) was normal at 2 weeks old but was reduced by 4 and 8 weeks old in mutants, and the stria vascularis, which generates the EP, showed degenerative changes. Three independent mouse knockout alleles of S1pr2 have been described previously, but this is the first time that a reduced EP has been reported. Genomic markers close to the human S1PR2 gene were significantly associated with auditory thresholds in the 1958 British Birth Cohort (n = 6099), suggesting involvement of S1P signalling in human hearing loss. The finding of early onset loss of EP gives new mechanistic insight into the disease process and suggests that therapies for humans with hearing loss due to S1P signalling defects need to target strial function. PMID- 27383013 TI - Structural studies of Schiff-base [2 + 2] macrocycles derived from 2,2' oxydianiline and the ROP capability of their organoaluminium complexes. AB - The molecular structures of a number of solvates of the [2 + 2] Schiff-base macrocycles {[2-(OH)-5-(R)-C6H2-1,3-(CH)2][O(2-C6H4N)2]}2 (R = Me L(1)H2, tBu L(2)H2, Cl L(3)H2), formed by reacting 2,6-dicarboxy-4-R-phenol with 2,2' oxydianiline (2-aminophenylether), (2-NH2C6H4)2O, have been determined. Reaction of L(n)H2 with two equivalents of AlR'3 (R' = Me, Et) afforded dinuclear alkylaluminium complexes [(AlR'2)2L(1-3)] (R = R' = Me (1), R = tBu, R' = Me (2), R = Cl, R' = Me (3), R = Me, R' = Et (4), R = tBu, R' = Et (5), R = Cl, R' = Et (6)). For comparative studies, reactions of two equivalents of AlR'3 (R' = Me, Et) with the macrocycle derived from 2,2'-ethylenedianiline and 2,6-dicarboxy-R phenols (R = Me L(4)H2, tBu L(5)H2) were conducted; the complexes [(AlMe)(AlMe2)L(5)].21/4MeCN (7.21/4MeCN) and [(AlEt2)2L(4)] (8) were isolated. Use of limited AlEt3 with L(3)H2 or L(5)H2 afforded mononuclear bis(macrocyclic) complexes [Al(L(3))(L(3)H)].4toluene (9.4toluene) and [Al(L(5))(L(5)H)].5MeCN (10.5MeCN), respectively. Use of four equivalents of AlR'3 led to transfer of alkyl groups and isolation of the complexes [(AlR'2)4L(1'-3')] (R = L(2'), R' = Me (11); L(3'), R' = Me (12); L(1'), R' = Et (13); L(2'), R' = Et (14); L(3'), R' = Et (15)), where L(1'-3') is the macrocycle resulting from double alkyl transfer to imine, namely {[2-(O)-5-(R)C6H2-1-(CH)-3-C(R')H][(O)(2-(N)-2'-C6H4N)2]}2. Molecular structures of complexes 7.21/4MeCN, 8, 9.4toluene, 10.5MeCN and 11.13/4toluene.11/4hexane are reported. These complexes act as catalysts for the ring opening polymerisation (ROP) of epsilon-caprolactone and rac-lactide; high conversions were achieved over 30 min at 80 degrees C for epsilon-caprolactone, and 110 degrees C over 12 h for rac-lactide. PMID- 27383014 TI - Security of quantum key distribution with multiphoton components. AB - Most qubit-based quantum key distribution (QKD) protocols extract the secure key merely from single-photon component of the attenuated lasers. However, with the Scarani-Acin-Ribordy-Gisin 2004 (SARG04) QKD protocol, the unconditionally secure key can be extracted from the two-photon component by modifying the classical post-processing procedure in the BB84 protocol. Employing the merits of SARG04 QKD protocol and six-state preparation, one can extract secure key from the components of single photon up to four photons. In this paper, we provide the exact relations between the secure key rate and the bit error rate in a six-state SARG04 protocol with single-photon, two-photon, three-photon, and four-photon sources. By restricting the mutual information between the phase error and bit error, we obtain a higher secure bit error rate threshold of the multiphoton components than previous works. Besides, we compare the performances of the six state SARG04 with other prepare-and-measure QKD protocols using decoy states. PMID- 27383015 TI - A carbon-free polyoxometalate molecular catalyst with a cobalt-arsenic core for visible light-driven water oxidation. AB - A carbon-free, stable, homogeneous water oxidation catalyst based on the unique hepta-nuclear cobalt-arsenic core ("fused" double-quasi-cubane) and polyoxometalate ligands, Na12[{Co(II)7As(III)6O9(OH)6}(A-alpha-SiW9O34)2].8H2O (1), was synthesized, thoroughly characterized and employed to catalyze water oxidation under visible-light-driven conditions. PMID- 27383016 TI - FGFs: crucial factors that regulate tumour initiation and progression. AB - Fibroblast growth factors (FGFs) are crucial signalling molecules involved in normal cell growth, differentiation and proliferation. Over the past few decades, a large body of research has illustrated effects of individual FGFs on tumour initiation and progression. Tumour development is commonly accompanied with generation of new blood and lymph vessels, which support enhanced cell proliferation. Moreover, acquisition of tumour cells of the epithelial mesenchymal transition (EMT) phenotype, enhances tumour cell migration and invasion potentials, crucial steps in tumour metastasis. This review summarizes recent findings concerning roles of FGFs in angiogenesis, lymphangiogenesis and EMT. PMID- 27383017 TI - Factor predicting total nucleated cell counts in cord blood units. AB - BACKGROUND: Cord blood (CB) stem cells have been used worldwide in transplant medicine to treat various diseases. The efficacy of stem cells in umbilical CB (UCB) can be predicted by the number of total nucleated cells (TNCs). To optimize the clinical use of stem cells in our population, this study addresses several variables affecting the TNC count. STUDY DESIGN AND METHODS: This observational, cross-sectional study was conducted in a single center from 2012 to 2014. In total, 957 CB units (CBUs) were collected from consented mothers. Data analyses of clinically accepted CBUs were correlated with maternal and infant factors. RESULTS: Based on the TNC accepted level of banking, 188 CBUs (19.64%) were rejected. Of the 16 maternal and infant variables evaluated, three factors demonstrated a statistically significant predictive value for the accepted TNC level. CB volume was the best predictive factor (p <= 0.0001), followed by newborn birth weight (p = 0.025), and the method of delivery (p = 0.002). CONCLUSIONS: Several maternal, neonatal, and obstetric factors appear to play a major role in predicting an accepted TNC count, which can be used to improve criteria for the donation of stem cells in CBUs. PMID- 27383018 TI - A new conservation strategy for China-A model starting with primates. AB - Although the evolutionary history of primates in China dates to the Eocene, and includes major radiations of lorisids, hominoids, cercopithecines, and colobines during the Miocene, Pliocene, and Pleistocene, extensive human-induced habitat change and deforestation over the past few centuries has resulted in 22 of 25 extant species listed as threatened or endangered, and two species of gibbons extirpated in the last few years. This commentary briefly reviews factors that have contributed to the decline of primates in China over the past 400 years, and in particular how major social events and economic development in modern China have resulted in unsustainable environmental change. In response, we describe our efforts to develop a strategic scientific, educational and conservation partnership in China, focusing on primates, in which GIS technology will be used to integrate geographical profiles, climatic information, and changes in land use patterns and human and nonhuman primate distributions to highlight issues of immediate concern and to develop priority-based conservation solutions. Our goal is to evaluate how human-induced environmental change has impacted primates over time and to predict the likelihood of primate population extinctions in the near future. This model represents an early warning system that will be widely available to the Chinese government, public, educational institutions, researchers, and NGOs through social media and educational videos in order to arouse public awareness and promote wildlife conservation. We encourage colleagues across a broad range of academic disciplines, political ideologies, and the public to help move this strategy into reality, the sooner the better. Am. J. Primatol. 78:1137-1148, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27383019 TI - Detection of the Cholera Toxin-binding Activity of kappa-Casein Macropeptide and Optimization of Its Production by the Response Surface Methodology. AB - The cholera toxin (CT)-binding activity of purified kappa-casein macropeptide (CMP) from bovine kappa-casein was detected. In addition, a statistical model was developed to optimize the production of CMP. CMP was prepared by chymosin hydrolysis of kappa-casein and a subsequent 3% trichloroacetic acid treatment. CMP was further fractionated in an ion-exchange column by FPLC. CT binding activity was eluted at 0.18 M NaCl and was a single 8.9 kDa peptide without tyrosine and arginine residues. The CT binding activity was rapidly lost by a carbohydrase treatment. The conditions for CMP production with chymosin were optimized by using the response surface methodology (RSM). The estimated optimum levels of the factors were as follows: reaction temperature, 38.5 degrees C; pH, 6.44; and time, 35.9 min. A validation experiment was performed in which CMP was prepared under the predicted parameters, and it was ascertained that the estimated optimum conditions gave better production of CMP than any other conditions. PMID- 27383020 TI - Single-Molecule Magnets: Giant Hysteresis of Single-Molecule Magnets Adsorbed on a Nonmagnetic Insulator (Adv. Mater. 26/2016). AB - In Tb(Pc)2 single-molecule magnets, where Pc is phthalocyanine, adsorbed on magnesium oxide, the fluctuations of the terbium magnetic moment are strongly suppressed in contrast to the adsorption on silver. On page 5195, J. Dreiser and co-workers investigate that the molecules are perfectly organized by self assembly, as seen in the scanning tunnelling microscopy image (top part of the design). The molecules are probed by circularly polarized X-rays depicted as green spirals. PMID- 27383022 TI - A Soft 3D Acoustic Metafluid with Dual-Band Negative Refractive Index. PMID- 27383023 TI - Flexible Supercapacitors: A Simple Approach to Boost Capacitance: Flexible Supercapacitors Based on Manganese Oxides@MOFs via Chemically Induced In Situ Self-Transformation (Adv. Mater. 26/2016). AB - W.-Y. Lai, H. Pang, W. Huang, and co-workers present a simple and effective method for transforming nanocubic MOFs (metal-organic frameworks) into MnOx nanoflower-decorated MOFs. This liquid-phase method is metaphorically illustrated by the ocean background, as is the transformation process by the different cubes. The application of these materials in flexible supercapacitors is further described on page 5242. PMID- 27383024 TI - Supercapacitors: A Hierarchical Carbon Derived from Sponge-Templated Activation of Graphene Oxide for High-Performance Supercapacitor Electrodes (Adv. Mater. 26/2016). AB - H. Ji, Y. Zhu, and co-workers demonstrate a 3D hierarchically porous carbon by introducing a polyurethane sponge to template graphene oxide into a 3D interconnected structure while KOH activation generates abundant micropores in its backbone. As described on page 5222, a supercapacitor assembled with this carbon material achieves a high energy density of 89 W h kg(-1) (64 W h L(-1) ) and outstanding power density due to its shortened ion transport distance in three dimensions. PMID- 27383025 TI - Microspheres: Microfluidic Generation of Monodisperse and Photoreconfigurable Microspheres for Floral Iridescence-Inspired Structural Colorization (Adv. Mater. 26/2016). AB - Flowering plants have advanced their colorization strategies to divide incoming white light into spatially sequenced vivid colors, especially by using 2D grating diffractive motifs. On page 5268, P. J. Yoo, S. Lee, and co-workers conceive a new idea for a microfluidic approach to mimic this wonderful biological strategy and its practical application to the color encoding of colloidal particles. PMID- 27383027 TI - Dielectrophoretic behaviours of microdroplet sandwiched between LN substrates. AB - We demonstrate a sandwich configuration for microfluidic manipulation in LiNbO3 platform based on photovoltaic effect, and the behaviours of dielectric microdroplet under this sandwich configuration are investigated. It is found that the microdroplet can generate in the form of liquid bridge inside the LiNbO3 based sandwich structure under the governing dielectrophoretic force, and the dynamic process of microdroplet generation highly depends on the substrate combinations. Dynamic features found for different combinations are explained by the different electrostatic field distribution basing on the finite-element simulation results. Moreover, the electrostatic field required by the microdroplet generation is estimated through meniscus evolution and it is found in good agreement with the simulated electrostatic field inside the sandwich gap. Several kinds of microdroplet manipulations are attempted in this work. We suggest that the local dielectrophoretic force acting on the microdroplet depends on the distribution of the accumulated irradiation dosage. Without using any additional pumping or jetting actuator, the microdroplet can be step-moved, deformed or patterned by the inconsecutive dot-irradiation scheme, as well as elastically stretched out and back or smoothly guided in a designed pass by the consecutive line-irradiation scheme. PMID- 27383028 TI - Two-Dimensional Phosphorus Oxides as Energy and Information Materials. AB - Phosphorene is a rising star in electronics. Recently, 2D phosphorus oxides with higher stability have been synthesized. In this study, we theoretically explored the structures and properties of 2D phosphorus oxides. We found that the structural features of Px Oy vary with the oxygen content. When the oxygen content is low, the most stable Px Oy material can be obtained by the adsorption of O atoms on phosphorene. Otherwise, stable structures are no longer based on phosphorene and will contain P-O-P motifs. We found that P4 O4 has a direct band gap (about 2.24 eV), good optical absorption, and high stability in water, so it may be suitable for photochemical water splitting. P2 O3 adopts two possible stable ferroelectric structures (P2 O3 -I and P2 O3 -II) with electric polarization perpendicular and parallel to the lateral plane, respectively, as the lowest-energy configurations, depending on the layer thickness. We propose that P2 O3 could be used in novel nanoscale multiple-state memory devices. PMID- 27383029 TI - Comparison of Differing Clinical Schedules for Nursing Students. AB - Maximizing student clinical schedules involves a range of nurse educator activities including scheduling, placement, and learning activity construction. The purpose of this study was to compare opportunities for students to develop their psychomotor skills on the clinical unit and perceptions of clinical experiences across 6-hour day, 6-hour evening, and 12-hour day schedules in an acute care setting. The main finding was that 12-hour schedules provided an overall significantly higher rate of skill opportunities than either of the other 6-hour schedules. PMID- 27383030 TI - Does the Interpersonal Model Generalize to Obesity Without Binge Eating? AB - The interpersonal model has been validated for binge eating disorder (BED), but it is not yet known if the model applies to individuals who are obese but who do not binge eat. The goal of this study was to compare the validity of the interpersonal model in those with BED versus those with obesity, and normal weight samples. Data from a sample of 93 treatment-seeking women diagnosed with BED, 186 women who were obese without BED, and 100 controls who were normal weight were examined for indirect effects of interpersonal problems on binge eating psychopathology mediated through negative affect. Findings demonstrated the mediating role of negative affect for those with BED and those who were obese without BED. Testing a reverse model suggested that the interpersonal model is specific for BED but that this model may not be specific for those without BED. This is the first study to find support for the interpersonal model in a sample of women with obesity but who do not binge. However, negative affect likely plays a more complex role in determining overeating in those with obesity but who do not binge. Copyright (c) 2016 John Wiley & Sons, Ltd and Eating Disorders Association. PMID- 27383032 TI - Hierarchical Fabrication of Engineered Vascularized Bone Biphasic Constructs via Dual 3D Bioprinting: Integrating Regional Bioactive Factors into Architectural Design. AB - A biphasic artificial vascularized bone construct with regional bioactive factors is presented using dual 3D bioprinting platform technique, thereby forming a large functional bone grafts with organized vascular networks. Biocompatible mussel-inspired chemistry and "thiol-ene" click reaction are used to regionally immobilize bioactive factors during construct fabrication for modulating or improving cellular events. PMID- 27383033 TI - Heterogeneity of subclinical autistic traits among parents of children with autism spectrum disorder: Identifying the broader autism phenotype with a data driven method. AB - Clinical diagnosis of autism spectrum disorder (ASD) can be conceptualized as the extreme end of the distribution of subclinical autistic traits related to genetic susceptibility factors (broad autism phenotype (BAP)) in the general population. Subclinical autistic traits are significantly more common among unaffected first degree relatives of probands with autism. However, there is a significant heterogeneity of autistic traits in family members of individuals with ASD and severity of autistic traits are not significantly different from controls in the majority of these relatives. The current study investigated the heterogeneity of autistic traits using latent class analysis (LCA) of the Autism Spectrum Quotient (AQ) ratings of 673 parents of children with ASD and 147 parents of typically developing children. Two distinct subgroups, including a "low-scoring" and a "high-scorer (BAP)" groups, were found. In comparison to control parents, a significantly larger proportion (21.1% vs. 7.5%) of parents of ASD were members of BAP group. Communication subscale made a distinctive contribution to the separation of high and low-scoring groups (d = 2.77). Further studies investigating neurobiological and genetic biomarkers and stability of these two subgroups over time are important for understanding the nature of autistic traits in the general population. Autism Res 2017, 10: 321-326. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 27383034 TI - Interventions for managing weight change following paediatric acquired brain injury: a systematic review. AB - OBJECTIVE: To systematically review literature reporting interventions for weight change following paediatric acquired brain injury (ABI). METHOD: A systematic search of the literature was conducted using advanced search techniques. The retrieval identified 1562 papers, of which 30 were relevant. The total number of paediatric participants was 759. RESULTS: There is a paucity of higher quality evidence to support the use of weight change interventions following paediatric ABI. Substantial variation in screening, outcome measures, intervention, and reporting were demonstrated. Some support was found for the use of hypothalamic sparing surgery as a method to prevent obesity following craniopharyngioma resection. INTERPRETATION: There is a need for further study in this area to inform clinical and research practice; recommendations are given. PMID- 27383039 TI - Outcomes of vascularized versus non-vascularized lymph node transplant in animal models for lymphedema. Review of the literature. AB - Lymph node transfer has been performed to treat lymphedema for several years. The goal of this procedure is to provide a bridge between the lymphatic system distal and proximal to the lymph node dissection. There is a lack of consensus about the necessity of an additional vascular anastomosis for the transplanted lymph nodes. A systematic literature search in Cochrane Library database CENTRAL, MEDLINE, and EMBASE of animal studies using lymph node transplantation with and without additional vascularization was performed in March 2016. The strategy used for the search was: (("Models, Animal"[Mesh]) AND (("Lymphedema"[Mesh]) OR "Lymph Nodes"[Mesh]) OR "Lymph Node Excision"[Mesh])) AND ((vascularized lymph node transfer) OR ((non-vascularized lymph node transfer) OR lymph node graft)). The primary outcomes were: survival of transplanted lymph node and lymphatic vessel regeneration. Sixteen studies were included. Vascularization and the use of growth factors were significantly associated with lymph node survival. Lymphatic vessels regeneration was independent from vascularization. According to the results of the current study, additional vascular anastomosis might improve the transplanted lymph node survival. Further studies in both experimental and clinical setting are needed in order to support it. J. Surg. Oncol. 2017;115:32 36. (c) 2016 Wiley Periodicals, Inc. PMID- 27383040 TI - Generation of New Complestatin Analogues by Heterologous Expression of the Complestatin Biosynthetic Gene Cluster from Streptomyces chartreusis AN1542. AB - The heterologous expression of the biosynthetic gene cluster (BGC) of natural products enables the production of complex metabolites in a well-characterized host, and facilitates the generation of novel analogues by the manipulation of the genes. However, the BGCs of glycopeptides such as vancomycin, teicoplanin, and complestatin are usually too large to be directly cloned into a single cosmid. Here, we describe the heterologous expression of the complestatin BGC. The 54.5 kb cluster was fully reconstituted from two overlapping cosmids into one cosmid by lambda-RED recombination-mediated assembly. Heterologous expression of the assembled gene cluster in Streptomyces lividans TK24 resulted in the production of complestatin. Deletion of cytochrome P450 monooxygenase genes (open reading frames 10 and 11) and heterologous expression of the modified clusters led to the production of two new monocyclic and linear derivatives, complestatins M55 and S56. PMID- 27383041 TI - Encouraging professional scepticism in medical practice. AB - Complex cases constitute a considerable part of what medical practitioners have to deal with. In this paper, I refer specifically to instances that are complex as they are related to the profound epistemological problem of underdetermination. The underdetermination thesis states that theories are underdetermined by data, meaning that any set of data is logically compatible with different scientific theories. For the medical practitioners, this means that there is a risk that the analysis they give or the judgments they make might be incorrect. As being incorrect might lead to patients experiencing additional, more intense or prolonged suffering, it is very important that uncertainty is dealt with in a professional way. The ancient scepticism proposed by Sextus Empiricus and the professional scepticism in auditing of today both offer systematic approaches to what is uncertain that might work also in a medical setting. PMID- 27383042 TI - Long-term clinical course in three patients with MAMLD1 mutations. AB - Although MAMLD1 on chromosome Xq28 is known as a causative gene for 46,XY disorders of sex development, clinical information is virtually limited in patients of infancy to early childhood. Here, we report long-term genital and hormonal findings in three previously described Japanese patients with MAMLD1 mutations, i.e., patients 1 and 2 with p.E197X and patient 3 with p.R726X. As previously reported, patients 1-3 exhibited penoscrotal hypospadias with chordee, microphallus, bifid/hypoplastic scrotum, and/or bilateral cryptorchidism/retractile testes, in the presence of sufficiently high serum basal or hCG-stimulated testosterone values in the mini-pubertal period to early childhood. Subsequently, patient 1 had low serum hCG-stimulated testosterone value (126 ng/dL) at 13 11/12 years of age, and manifested microphallus (4.5 cm), relatively small testes (left 8 mL and right 10 mL), Tanner stage 3 genitalia and pubic hair development at 18 3/12 years of age. Similarly, patients 2 and 3 showed mild hypergonadotropic hypogonadism at 7 0/12 and 9 9/12 years of age, respectively, with serum GnRH-stimulated LH values of 5.5 and 7.2 mIU/mL and FSH values of 10.3 and 19.8 mIU/mL and hCG-stimulated testosterone values of 70 and 80 ng/dL, respectively. Testis ultrasound studies delineated microlithiasis in patients 1 and 3. These results imply for the first time deterioration of testicular function with age in patients with pathologic MAMLD1 mutations. PMID- 27383043 TI - Both cancerous miR-21 and stromal miR-21 in urothelial carcinoma are related to tumour progression. AB - AIMS: Urothelial carcinoma (UC) is a globally common cancer. miR-21 appears to be important in the tumorigenesis of almost all types of human cancer. However, its precise localization and significance in UC have yet to be clarified. The aim of this study was to examine miR-21 expression in UC and reveal its clinicopathological importance. METHODS AND RESULTS: Tissue arrays of 232 UCs were examined for miR-21 by the use of in-situ hybridization. One hundred and forty-eight transurethral resection specimens and 84 surgically resected specimens were used. After miR-21 positivity had been evaluated separately in tumour cells and the tumour stroma, it was compared with clinicopathological factors and overall survival. miR-21 was strongly expressed in tumour cells in 9% of cases and in the tumour stroma in 6% of cases. Stromal miR-21 positivity was lower than that of cancerous miR-21. Both miR-21s were correlated with each other and related to tumour stage, locus, and histological grade. In addition, strong positivity of miR-21 in cancer and the stroma was significantly related to poorer prognosis among surgically resected cases. In a Cox proportional hazard model, cancerous miR-21 was the only independent prognostic factor except for tumour stage. CONCLUSIONS: miR-21 in both cancer and stromal cells is closely related to tumour progression in UC. miR-21 may be a prognostic marker for cancer progression. PMID- 27383044 TI - Inherited Thrombotic Thrombocytopenic Purpura (Upshaw Schulman Syndrome) as Differential Diagnosis to Neonatal Septicaemia with Disseminated Intravascular Coagulation - a Case Series. AB - We report on 3 male neonates with hereditary ADAMTS13 deficiency (Upshaw Schulman syndrome, USS), the inherited form of thrombotic thrombocytopenic purpura (TTP). 2 presented shortly after birth with thrombocytopenia followed by microangiopathic Coombs-negative haemolytic anaemia. Both initially received antibiotic treatment for suspected infection-associated thrombocytopenia. In one patient's brother, the first bout of incipient TTP did not occur before 6 months of age, despite the same genetic defect. ADAMTS13 activity was<5%, compound heterozygous mutations were found in all patients. USS constitutes a differential diagnosis to thrombocytopenia caused by disseminated intravascular coagulation in neonatal septicaemia. Administration of fresh frozen plasma usually resolves acute bouts of the disease. In some cases of thrombocytopenia of unknown origin in infancy, the resolution of signs and symptoms after infusion of plasma may point towards the diagnosis. PMID- 27383045 TI - Atypia of undetermined significance on thyroid fine needle aspiration - risk factors for malignancy. AB - OBJECTIVES: This study is designed to determine the clinical predictors of malignancy in the atypia of undetermined significance (AUS) category resulted from thyroid fine needle aspiration (FNA). DESIGN: Retrospective cohort study. SETTING: Dong-A University Medical Center, Busan, Korea. PARTICIPANTS: Sixty-two patients who underwent thyroid surgery from January 2010 to December 2013, following a diagnosis of AUS from preoperative thyroid FNA. MAIN OUTCOME MEASURES: We investigated the age, gender, maximum size and site of the nodules, ultrasonographic findings, cytological features, BRAF gene mutation, surgical method, number of AUS on repeated FNA and final pathologic results. RESULTS: Forty-one of sixty-two patients underwent total thyroidectomy and the rest had lobectomy. The final pathologic results were 41 malignancies and 21 benign diseases. Nodules less than 1.5 cm, ultrasonographic findings suggestive of malignancy were risk factors for malignancy on univariated analysis (P < 0.001). Multivariated analysis showed that nodules less than 1.5 cm, ultrasonographic findings suggestive of malignancy and more than 2 results of atypia from repeated FNAs were significant risk factors for malignancy (P < 0.001). A BRAF gene mutation analysis was performed in 38 patients, and 13 patients had the mutation. All patients with the BRAF gene mutation had been diagnosed with papillary thyroid cancer (P > 0.05). CONCLUSIONS: We recommend close observation or diagnostic surgery in patients with nodules <1.5 cm and with two or more malignant ultrasound feature and a BRAF mutation, or with two or more AUS findings on repeated FNAs. PMID- 27383046 TI - Sensory analysis of cosmetic powders: personal care ingredients and emulsions. AB - OBJECTIVE: The powders are ingredients increasingly used in the formulation of cosmetic products for the sensory qualities they give. The objective of this study was the development of a lexicon and a referential for sensory characterization of these pure raw materials as well as formulations which contain them. METHODS: Eleven expert panellists from Ecole de biologie industrielle de Cergy (France) developed a lexicon and a referential based on 12 powders of different chemical natures. The selected attributes were then used for performing a quantitative descriptive profile of two powders and an emulsion containing or not one of these two powders. RESULTS: A lexicon has been established through a consensus approach of the panel. It contains seven attributes that allow the evaluation of the powders in four phases: the appearance, the pickup, the application and the after-feel. This lexicon contains definitions and assessment protocols and provides references products. The quantitative descriptive profile of two powders of the same chemical nature, but different in physical quality showed significant differences in sensory level between products. These same attributes used to evaluate an emulsion containing the powder or not allowed to prove the contribution of these raw materials on the sensory specificities of the emulsion. CONCLUSION: The lexicon developed in this study can be used for assessment of other powders but also to define the quantities necessary to put in the formulation to meet the sensory characteristics of these raw materials powder. PMID- 27383047 TI - Mps1 kinase regulates tumor cell viability via its novel role in mitochondria. AB - Targeting mitotic kinase monopolar spindle 1 (Mps1) for tumor therapy has been investigated for many years. Although it was suggested that Mps1 regulates cell viability through its role in spindle assembly checkpoint (SAC), the underlying mechanism remains less defined. In an endeavor to reveal the role of high levels of mitotic kinase Mps1 in the development of colon cancer, we unexpectedly found the amount of Mps1 required for cell survival far exceeds that of maintaining SAC in aneuploid cell lines. This suggests that other functions of Mps1 besides SAC are also employed to maintain cell viability. Mps1 regulates cell viability independent of its role in cytokinesis as the genetic depletion of Mps1 spanning from metaphase to cytokinesis affects neither cytokinesis nor cell viability. Furthermore, we developed a single-cycle inhibition strategy that allows disruption of Mps1 function only in mitosis. Using this strategy, we found the functions of Mps1 in mitosis are vital for cell viability as short-term treatment of mitotic colon cancer cell lines with Mps1 inhibitors is sufficient to cause cell death. Interestingly, Mps1 inhibitors synergize with microtubule depolymerizing drug in promoting polyploidization but not in tumor cell growth inhibition. Finally, we found that Mps1 can be recruited to mitochondria by binding to voltage-dependent anion channel 1 (VDAC1) via its C-terminal fragment. This interaction is essential for cell viability as Mps1 mutant defective for interaction fails to main cell viability, causing the release of cytochrome c. Meanwhile, deprivation of VDAC1 can make tumor cells refractory to loss of Mps1 induced cell death. Collectively, we conclude that inhibition of the novel mitochondrial function Mps1 is sufficient to kill tumor cells. PMID- 27383048 TI - Post-translational modifications as key regulators of TNF-induced necroptosis. AB - Necroptosis is a novel form of programmed cell death that is independent of caspase activity. Different stimuli can trigger necroptosis. At present, the most informative studies about necroptosis derive from the tumor necrosis factor (TNF) triggered system. The initiation of TNF-induced necroptosis requires the kinase activity of receptor-interacting protein 1 and 3 (RIP1 and RIP3). Evidence now reveals that the ability of RIP1 and RIP3 to modulate this key cellular event is tightly controlled by post-translational modifications, including ubiquitination, phosphorylation, caspase 8-mediated cleavage and GlcNAcylation. These regulatory events coordinately determine whether a cell will survive or die by apoptosis or necroptosis. In this review, we highlight recent advances in the study of post translational modifications during TNF-induced necroptosis and discuss how these modifications regulate the complex and delicate control of programmed necrosis. PMID- 27383049 TI - Safety profile of repeated rituximab cycles in unselected rheumatoid arthritis patients: a long-term, prospective real-life study. AB - OBJECTIVES: To evaluate the long-term safety of rituximab (RTX) in rheumatoid arthritis (RA) patients in daily clinical practice. METHODS: This was a multicentre (17 Greek Rheumatology sites), prospective, long-term, pharmacovigilance study of patients with moderate to severe RA and an inadequate response or intolerance to >=1 anti-tumour necrosis factor (TNF) agents. Adverse events (AEs) were recorded and collected prospectively every 2-6 months. RESULTS: 234 patients (mean age: 59+/-12.5, 79.5% women, mean DAS28: 5.35+/-1.32) were included and followed for 27.7 months (median). The overall AEs, serious AE (SAEs) and serious infection (SIEs) rate were 48.36, 6.68 and 2.53/100 patient years, respectively. Three cases of hepatitis B virus (HBV) reactivation were recorded (two in chronic and one in past HBV infection). Withdrawals due to AEs (5.6%) occurred more frequently during the first cycles of RTX therapy while repeated RTX cycles were not associated with an increased risk of AEs. There were 3 deaths with an incidence rate of 0.69/100 patient-years. Age >=65 years was associated with a higher incidence rate ratio of AEs and SAEs as compared to <65 years (1.53, p=0.002 and 2.88, p=0.005, respectively). Drug retention rate during 434.28 patient-years of follow-up was 57.3%. Factors associated with drug discontinuation by multivariate analysis included age, baseline swollen joint count and no use of concomitant methotrexate therapy. CONCLUSIONS: Long-term RTX therapy in a real-life RA cohort, did not reveal any new safety issues. Advanced age was associated with increased risk of AEs and premature drug discontinuation. PMID- 27383051 TI - The proposed channel-enzyme transient receptor potential melastatin 2 does not possess ADP ribose hydrolase activity. AB - Transient Receptor Potential Melastatin 2 (TRPM2) is a Ca(2+)-permeable cation channel essential for immunocyte activation, insulin secretion, and postischemic cell death. TRPM2 is activated by ADP ribose (ADPR) binding to its C-terminal cytosolic NUDT9-homology (NUDT9H) domain, homologous to the soluble mitochondrial ADPR pyrophosphatase (ADPRase) NUDT9. Reported ADPR hydrolysis classified TRPM2 as a channel-enzyme, but insolubility of isolated NUDT9H hampered further investigations. Here we developed a soluble NUDT9H model using chimeric proteins built from complementary polypeptide fragments of NUDT9H and NUDT9. When expressed in E.coli, chimeras containing up to ~90% NUDT9H sequence remained soluble and were affinity-purified. In ADPRase assays the conserved Nudix-box sequence of NUDT9 proved essential for activity (kcat~4-9s(-1)), that of NUDT9H did not support catalysis. Replacing NUDT9H in full-length TRPM2 with soluble chimeras retained ADPR-dependent channel gating (K1/2~1-5 MUM), confirming functionality of chimeric domains. Thus, TRPM2 is not a 'chanzyme'. Chimeras provide convenient soluble NUDT9H models for structural/biochemical studies. PMID- 27383050 TI - Metabolic network rewiring of propionate flux compensates vitamin B12 deficiency in C. elegans. AB - Metabolic network rewiring is the rerouting of metabolism through the use of alternate enzymes to adjust pathway flux and accomplish specific anabolic or catabolic objectives. Here, we report the first characterization of two parallel pathways for the breakdown of the short chain fatty acid propionate in Caenorhabditis elegans. Using genetic interaction mapping, gene co-expression analysis, pathway intermediate quantification and carbon tracing, we uncover a vitamin B12-independent propionate breakdown shunt that is transcriptionally activated on vitamin B12 deficient diets, or under genetic conditions mimicking the human diseases propionic- and methylmalonic acidemia, in which the canonical B12-dependent propionate breakdown pathway is blocked. Our study presents the first example of transcriptional vitamin-directed metabolic network rewiring to promote survival under vitamin deficiency. The ability to reroute propionate breakdown according to B12 availability may provide C. elegans with metabolic plasticity and thus a selective advantage on different diets in the wild. PMID- 27383053 TI - Motivation Mediates the Perfectionism-Burnout Relationship: A Three-Wave Longitudinal Study With Junior Athletes. AB - Perfectionism in sports has been shown to predict longitudinal changes in athlete burnout. What mediates these changes over time, however, is still unclear. Adopting a self-determination theory perspective and using a three-wave longitudinal design, the current study examined perfectionistic strivings, perfectionistic concerns, autonomous motivation, controlled motivation, and athlete burnout in 141 junior athletes (mean age = 17.3 years) over 6 months of active training. When multilevel structural equation modeling was employed to test a mediational model, a differential pattern of between- and within-person relationships emerged. Whereas autonomous motivation mediated the negative relationship that perfectionistic strivings had with burnout at the between- and within-person level, controlled motivation mediated the positive relationship that perfectionistic concerns had with burnout at the between-persons level only. The present findings suggest that differences in autonomous and controlled motivation explain why perfectionism predicts changes in athlete burnout over time. PMID- 27383054 TI - Multivariate and Cladistic Analyses of Isolated Teeth Reveal Sympatry of Theropod Dinosaurs in the Late Jurassic of Northern Germany. AB - Remains of theropod dinosaurs are very rare in Northern Germany because the area was repeatedly submerged by a shallow epicontinental sea during the Mesozoic. Here, 80 Late Jurassic theropod teeth are described of which the majority were collected over decades from marine carbonates in nowadays abandoned and backfilled quarries of the 19th century. Eighteen different morphotypes (A-R) could be distinguished and 3D models based on micro-CT scans of the best examples of all morphotypes are included as supplements. The teeth were identified with the assistance of discriminant function analysis and cladistic analysis based on updated datamatrices. The results show that a large variety of theropod groups were present in the Late Jurassic of northern Germany. Identified specimens comprise basal Tyrannosauroidea, as well as Allosauroidea, Megalosauroidea cf. Marshosaurus, Megalosauridae cf. Torvosaurus and probably Ceratosauria. The formerly reported presence of Dromaeosauridae in the Late Jurassic of northern Germany could not be confirmed. Some teeth of this study resemble specimens described as pertaining to Carcharodontosauria (morphotype A) and Abelisauridae (morphotype K). This interpretation is however, not supported by discriminant function analysis and cladistic analysis. Two smaller morphotypes (N and Q) differ only in some probably size-related characteristics from larger morphotypes (B and C) and could well represent juveniles of adult specimens. The similarity of the northern German theropods with groups from contemporaneous localities suggests faunal exchange via land-connections in the Late Jurassic between Germany, Portugal and North America. PMID- 27383052 TI - A large fraction of neocortical myelin ensheathes axons of local inhibitory neurons. AB - Myelin is best known for its role in increasing the conduction velocity and metabolic efficiency of long-range excitatory axons. Accordingly, the myelin observed in neocortical gray matter is thought to mostly ensheath excitatory axons connecting to subcortical regions and distant cortical areas. Using independent analyses of light and electron microscopy data from mouse neocortex, we show that a surprisingly large fraction of cortical myelin (half the myelin in layer 2/3 and a quarter in layer 4) ensheathes axons of inhibitory neurons, specifically of parvalbumin-positive basket cells. This myelin differs significantly from that of excitatory axons in distribution and protein composition. Myelin on inhibitory axons is unlikely to meaningfully hasten the arrival of spikes at their pre-synaptic terminals, due to the patchy distribution and short path-lengths observed. Our results thus highlight the need for exploring alternative roles for myelin in neocortical circuits. PMID- 27383055 TI - Evolution of Canada's Boreal Forest Spatial Patterns as Seen from Space. AB - Understanding the development of landscape patterns over broad spatial and temporal scales is a major contribution to ecological sciences and is a critical area of research for forested land management. Boreal forests represent an excellent case study for such research because these forests have undergone significant changes over recent decades. We analyzed the temporal trends of four widely-used landscape pattern indices for boreal forests of Canada: forest cover, largest forest patch index, forest edge density, and core (interior) forest cover. The indices were computed over landscape extents ranging from 5,000 ha (n = 18,185) to 50,000 ha (n = 1,662) and across nine major ecozones of Canada. We used 26 years of Landsat satellite imagery to derive annualized trends of the landscape pattern indices. The largest declines in forest cover, largest forest patch index, and core forest cover were observed in the Boreal Shield, Boreal Plain, and Boreal Cordillera ecozones. Forest edge density increased at all landscape extents for all ecozones. Rapidly changing landscapes, defined as the 90th percentile of forest cover change, were among the most forested initially and were characterized by four times greater decrease in largest forest patch index, three times greater increase in forest edge density, and four times greater decrease in core forest cover compared with all 50,000 ha landscapes. Moreover, approximately 18% of all 50,000 ha landscapes did not change due to a lack of disturbance. The pattern database results provide important context for forest management agencies committed to implementing ecosystem-based management strategies. PMID- 27383056 TI - Stiffness of the microenvironment upregulates ERBB2 expression in 3D cultures of MCF10A within the range of mammographic density. AB - The effects of the stiffness of the microenvironment on the molecular response of 3D colony organization, at the maximum level of mammographic density (MD), are investigated. Phenotypic profiling reveals that 3D colony formation is heterogeneous and increased stiffness of the microenvironment, within the range of the MD, correlates with the increased frequency of aberrant 3D colony formation. Further integrative analysis of the genome-wide transcriptome and phenotypic profiling hypothesizes overexpression of ERBB2 in the premalignant MCF10A cell lines at a stiffness value that corresponds to the collagen component at high mammographic density. Subsequently, ERBB2 overexpression has been validated in the same cell line. Similar experiments with a more genetically stable cell line of 184A1 also revealed an increased frequency of aberrant colony formation with the increased stiffness; however, 184A1 did not demonstrate overexpression of ERBB2 at the same stiffness value of the high MD. These results suggest that stiffness exacerbates premalignant cell line of MCF10A. PMID- 27383058 TI - Finite-size effect on evolution of Griffiths phase in manganite nanoparticles. AB - The finite-size effect on the evolution of the Griffiths phase (GP) is studied using nanoparticles of half-doped manganite Pr0.5Sr0.5MnO3 with different average particle sizes but with similar structural parameters. All the samples exhibit pronounced GP behavior. With reducing the particle size, the Griffiths temperature remains almost unchanged but the characteristic critical temperature [Formula: see text] decreases and the GP properties are strengthened. It is noteworthy that the shift of [Formula: see text] follows finite-size scaling with the particle size revealing an exotic interplay between the GP properties and the sample dimension. This reinforces an earlier proposal of length-scale related evolution of GP. PMID- 27383057 TI - Overexpression of Mycothiol Disulfide Reductase Enhances Corynebacterium glutamicum Robustness by Modulating Cellular Redox Homeostasis and Antioxidant Proteins under Oxidative Stress. AB - Mycothiol (MSH) is the dominant low-molecular-weight thiol (LMWT) unique to high (G+C)-content Gram-positive Actinobacteria, such as Corynebacterium glutamicum, and is oxidised into its disulfide form mycothiol disulfide (MSSM) under oxidative conditions. Mycothiol disulfide reductase (Mtr), an NADPH-dependent enzyme, reduces MSSM to MSH, thus maintaining intracellular redox homeostasis. In this study, a recombinant plasmid was constructed to overexpress Mtr in C. glutamicum using the expression vector pXMJ19-His6. Mtr-overexpressing C. glutamicum cells showed increased tolerance to ROS induced by oxidants, bactericidal antibiotics, alkylating agents, and heavy metals. The physiological roles of Mtr in resistance to oxidative stresses were corroborated by decreased ROS levels, reduced carbonylation damage, decreased loss of reduced protein thiols, and a massive increase in the levels of reversible protein thiols in Mtr overexpressing cells exposed to stressful conditions. Moreover, overexpression of Mtr caused a marked increase in the ratio of reduced to oxidised mycothiol (MSH:MSSM), and significantly enhanced the activities of a variety of antioxidant enzymes, including mycothiol peroxidase (MPx), mycoredoxin 1 (Mrx1), thioredoxin 1 (Trx1), and methionine sulfoxide reductase A (MsrA). Taken together, these results indicate that the Mtr protein functions in C. glutamicum by protecting cells against oxidative stress. PMID- 27383059 TI - Maternal Age at Delivery Is Associated with an Epigenetic Signature in Both Newborns and Adults. AB - Offspring of older mothers are at increased risk of adverse birth outcomes, childhood cancers, type 1 diabetes, and neurodevelopmental disorders. The underlying biologic mechanisms for most of these associations remain obscure. One possibility is that maternal aging may produce lasting changes in the epigenetic features of a child's DNA. To test this, we explored the association of mothers' age at pregnancy with methylation in her offspring, using blood samples from 890 Norwegian newborns and measuring DNA methylation at more than 450,000 CpG sites across the genome. We examined replication of a maternal-age finding in an independent group of 1062 Norwegian newborns, and then in 200 US middle-aged women. Older maternal age was significantly associated with reduced methylation at four adjacent CpGs near the 2nd exon of KLHL35 in newborns (p-values ranging from 3x10-6 to 8x10-7). These associations were replicated in the independent set of newborns, and replicated again in women 40 to 60 years after their birth. This study provides the first example of parental age permanently affecting the epigenetic profile of offspring. While the specific functions of the affected gene are unknown, this finding opens the possibility that a mother's age at pregnancy could affect her child's health through epigenetic mechanisms. PMID- 27383061 TI - Reply to "Improving Coccyx Radiographs in Emergency Departments". PMID- 27383060 TI - Temporomandibular joint involvement in childhood arthritis: comparison of ultrasonography-assessed capsular width and MRI-assessed synovitis. AB - OBJECTIVES: Ultrasonography is an effective, low-cost, low-threshold and convenient diagnostic tool in childhood arthritis, but its value in temporomandibular joint (TMJ) involvement is not clear. The purpose of our study was to explore the reliability of ultrasonography to assess TMJ inflammation using contrast-enhanced MRI as reference standard, in order to deduce cut-off values for TMJ capsular width to detect enhanced synovial thickening (synovitis). METHODS: 124 ultrasonography and MRI examinations in 55 patients [mean age 12.4 +/- 3.5 years (+/-standard deviation)], the majority obtained within 1 day, were scored for subcondylar and condylar capsular width (ultrasonography images) and amount of synovitis (MR images). The correlations of these findings were calculated. A receiver operating characteristic (ROC) curve analysis, with MRI findings as reference standard, was obtained. RESULTS: The correlation between ultrasonography-assessed capsular width and MRI-assessed amount of synovitis was moderate both at the subcondylar and condylar level [Spearman's rho (rho): 0.483; p < 0.001 and 0.347; p < 0.001 respectively]. The ROC curve indicated the best discriminatory ability at the subcondylar level with an area under the curve of 0.77 (95% confidence interval 0.69-0.85) and a cut-off value of 1.2 mm (sensitivity 72%, specificity 70%) for the capsular width. CONCLUSIONS: A moderate correlation between ultrasonography-assessed capsular width and MRI assessed synovitis was found in childhood arthritis with the best discriminatory ability at the subcondylar level. This indicates that ultrasonography may be a valuable diagnostic tool in the initial assessment of TMJ inflammation. PMID- 27383062 TI - The Association Between Arterial Oxygen Tension and Neurological Outcome After Cardiac Arrest. AB - A number of observational studies have evaluated the association between arterial oxygen tensions and outcome after cardiac arrest with variable results. The objective of this study is to determine the association between arterial oxygen tension and neurological outcome after cardiac arrest. A retrospective cohort analysis was performed using the Penn Alliance for Therapeutic Hypothermia registry. Adult patients who experienced return of spontaneous circulation after in-hospital or out-of-hospital cardiac arrest (OHCA) and had a partial pressure of arterial oxygen (PaO2) recorded within 48 hours were included. Our primary exposure of interest was PaO2. Hyperoxemia was defined as PaO2 > 300 mmHg, hypoxemia as PaO2 < 60 mmHg, and optimal oxygenation as PaO2 60-300 mmHg. The primary outcome was neurological function at hospital discharge among survivors, as described by the cerebral performance category (CPC) score, dichotomized into "favorable" (CPCs 1-2) and "unfavorable" (CPCs 3-5). Secondary outcomes included in-hospital mortality. A total of 544 patients from 13 institutions were included. Average age was 61 years, 56% were male, and 51% were white. A total of 64% experienced OHCA, 81% of arrests were witnessed, and pulseless electrical activity was the most common initial rhythm (40%). More than 72% of the patients had cardiac etiology for their arrests, and 55% underwent targeted temperature management. A total of 38% of patients survived to hospital discharge. There was no significant association between PaO2 at any time interval and neurological outcome at hospital discharge. Hyperoxemia at 12 hours after cardiac arrest was associated with decreased odds of survival (OR 0.17 [0.03-0.89], p = 0.032). There was no significant association between arterial oxygen tension measured within the first 48 hours after cardiac arrest and neurological outcome. PMID- 27383063 TI - Preceding profound deafness and co-factors promote development of endolymphatic hydrops in preliminary patients with delayed endolymphatic hydrops. AB - CONCLUSION: Profound deafness (PD) is unlikely to be the only cause of endolymphatic hydrops (EH) in patients with delayed endolymphatic hydrops (DEH). Further studies in large patient cohorts are required to determine the etiologic co-factors involved in the development of EH in patients with PD and DEH. OBJECTIVES: DEH usually occurs in patients with sustained unilateral PD who then develop episodic vertigo or fluctuating hearing loss. The latency can vary markedly between PD and development of DEH, but the factors affecting inner ear homeostasis and causing EH during this latency period remain unclear. The study aimed to assess the differences in EH and functional status of the inner ear between patients with PD only and those with DEH. METHOD: Two PD and 10 DEH patients who had developed PD in early childhood were enrolled. Gadolinium enhanced magnetic resonance imaging of the inner ear was performed in all patients to assess the degree of EH in the vestibule and cochlea. RESULTS: There was no evidence of EH in the affected ears of patients with PD alone. DEH patients, however, showed significant EH in either the cochlea or vestibule, suggesting that EH development and DEH onset were strongly correlated. PMID- 27383064 TI - Estimation of pyrethroid pesticide intake using regression modeling of food groups based on composite dietary samples. AB - Population-based estimates of pesticide intake are needed to characterize exposure for particular demographic groups based on their dietary behaviors. Regression modeling performed on measurements of selected pesticides in composited duplicate diet samples allowed (1) estimation of pesticide intakes for a defined demographic community, and (2) comparison of dietary pesticide intakes between the composite and individual samples. Extant databases were useful for assigning individual samples to composites, but they could not provide the breadth of information needed to facilitate measurable levels in every composite. Composite sample measurements were found to be good predictors of pyrethroid pesticide levels in their individual sample constituents where sufficient measurements are available above the method detection limit. Statistical inference shows little evidence of differences between individual and composite measurements and suggests that regression modeling of food groups based on composite dietary samples may provide an effective tool for estimating dietary pesticide intake for a defined population. PMID- 27383065 TI - Actigraphy of Wrist and Ankle for Measuring Sleep Duration in Altitude Travelers. AB - : Latshang, Tsogyal Daniela, Daniela Juliana Mueller, Christian Maurizio Lo Cascio, Anne-Christin Stowhas, Katrin Stadelmann, Noemi Tesler, Peter Achermann, Reto Huber, Malcolm Kohler, and Konrad Ernst Bloch. Actigraphy of wrist and ankle for measuring sleep duration in altitude travelers. High Alt Med Biol. 17:194 202, 2016-Aims: Actigraphy might be convenient to assess sleep disturbances in altitude field studies. Therefore, we evaluated whether actigraphy accurately measures sleep duration in healthy subjects traveling to altitude. METHODS: Fifty one healthy men, aged mean +/- standard deviation (SD) 27 +/- 9 years, were studied during one night at Zurich (490 m), two nights at Davos Wolfgang (1630 m), and two nights at Jakobshorn (2590 m), in randomized order. Sleep duration measured by actigraphy, using a one-axis device at the wrist (n = 51), a three axis device at the other wrist, and a three-axis device at the ankle (n = 22), was compared with corresponding total sleep time (TST) measured by polysomnography. RESULTS: During 255 polysomnographic overnight studies, 449 paired actigraphic recordings were obtained. The median polysomnographic-derived TST ranged from 397 to 408 minutes. Actigraphic mean TST from wrists with one axis and three-axis devices, and from ankle agreed well with polysomnographic values with a bias of +1, -7, +6 minutes, respectively. Corresponding limits of agreement (+/-2 SD of bias) were +/-51, +/-60, and +/-59 minutes. Limits of agreement of mean TST over five nights by actigraphy and polysomnography were similar to the coefficient of repeatability (2 SD of mean) of polysomnographic TST, that is, +/-31, +/-38, and +/-36 minutes versus +/-34 minutes. CONCLUSIONS: Actigraphy of the wrist or ankle by a one-axis or a three-axis device accurately estimates mean TST in groups of subjects and mean TST over several nights in individuals traveling to altitude. Therefore, actigraphy is valuable for assessing effects of altitude and other environmental influences on sleep duration during field studies over extended periods. PMID- 27383066 TI - Interactive Organization of the Circadian Core Regulators PER2, BMAL1, CLOCK and PML. AB - The BMAL1 and CLOCK heterodimer in the mammalian circadian transcriptional complex is thought to be repressed by PER2 and CRY1 via direct interactions. We recently reported that PER2 is largely cytosolic in Pml(-/-) cells and did not co immunoprecipitate (co-IP) with BMAL1 or CLOCK. Here, using multi-color immunofluorescence (IF) staining and co-IP, we observed a nuclear distribution of BMAL1 and a predominately cytosolic distribution of CLOCK in Pml(-/-) MEF. In the presence of WT PML, PER2 co-localized with BMAL1 in the nucleus. In Pml(-/-) MEF transfected with mutant K487R PML, we observed that BMAL1 and PER2 co-localized with K487R PML in the cytosol. Furthermore, cytosolic CLOCK and PER2 displayed a significant non-overlapping IF staining pattern. In Bmal1(-/-) MEF, CLOCK was primarily cytosolic while PML and PER2 were nuclear. Together, our studies suggest that PML mediates the binding of PER2 to BMAL1 in the BMAL1/CLOCK heterodimer and is an important component in the organization of a functional clock complex in the nucleus. Our studies also support that BMAL1 is important for CLOCK nuclear localization. PMID- 27383067 TI - Permutation Machines. AB - We define a new inversion-based machine called a permuton of n genetic elements, which allows the n elements to be rearranged in any of the n.(n - 1).(n - 2)...2 = n! distinct orderings. We present two design algorithms for architecting such a machine. We define a notion of a feasible design and use the framework to discuss the feasibility of the permuton architectures. We have implemented our design algorithms in a freely usable web-accessible software for exploration of these machines. Permutation machines could be used as memory elements or state machines and explicitly illustrate a rational approach to designing biological systems. PMID- 27383071 TI - Symbols of pride or prejudice? Examining the impact of Native American sports mascots on stereotype application. AB - For over 50 years, a debate has existed over the use of Native American sports mascots; however, few empirical studies on the topic exist. The present study examined if supraliminal exposure to Native American mascots results in the application of negative stereotypes toward Native American people. Results indicated that the effect of Native American mascots was moderated by people's racial attitudes toward Native people. When exposed to Native mascots, people with a prejudiced attitude rated a Native American individual more stereotypically aggressive than those with a non-prejudiced attitude. However, this pattern did not occur when people were exposed to White mascots or neutral images. Furthermore, this pattern was not evident when people evaluated a non Native individual. This overall pattern of results indicates that Native American mascots selectively facilitate the application of negative stereotypes, resulting in harmful evaluations of Native American people. PMID- 27383069 TI - Axonal Dysfunction Precedes Motor Neuronal Death in Amyotrophic Lateral Sclerosis. AB - Wide-spread fasciculations are a characteristic feature in amyotrophic lateral sclerosis (ALS), suggesting motor axonal hyperexcitability. Previous excitability studies have shown increased nodal persistent sodium conductances and decreased potassium currents in motor axons of ALS patients, both of the changes inducing hyperexcitability. Altered axonal excitability potentially contributes to motor neuron death in ALS, but the relationship of the extent of motor neuronal death and abnormal excitability has not been fully elucidated. We performed multiple nerve excitability measurements in the median nerve at the wrist of 140 ALS patients and analyzed the relationship of compound muscle action potential (CMAP) amplitude (index of motor neuronal loss) and excitability indices, such as strength-duration time constant, threshold electrotonus, recovery cycle and current-threshold relationships. Compared to age-matched normal controls (n = 44), ALS patients (n = 140) had longer strength-duration time constant (SDTC: a measure of nodal persistent sodium current; p < 0.05), greater threshold changes in depolarizing threshold electrotonus (p < 0.05) and depolarizing current threshold relationship (i.e. less accommodation; (p < 0.05), greater superexcitability (a measure of fast potassium current; p < 0.05) and reduced late subexcitability (a measure of slow potassium current; p < 0.05), suggesting increased persistent sodium currents and decreased potassium currents. The reduced potassium currents were found even in the patient subgroups with normal CMAP (> 5mV). Regression analyses showed that SDTC (R = -0.22) and depolarizing threshold electrotonus (R = -0.22) increased with CMAP decline. These findings suggest that motor nerve hyperexcitability occurs in the early stage of the disease, and precedes motor neuronal loss in ALS. Modulation of altered ion channel function could be a treatment option for ALS. PMID- 27383068 TI - Global Prevalence of Chronic Kidney Disease - A Systematic Review and Meta Analysis. AB - Chronic kidney disease (CKD) is a global health burden with a high economic cost to health systems and is an independent risk factor for cardiovascular disease (CVD). All stages of CKD are associated with increased risks of cardiovascular morbidity, premature mortality, and/or decreased quality of life. CKD is usually asymptomatic until later stages and accurate prevalence data are lacking. Thus we sought to determine the prevalence of CKD globally, by stage, geographical location, gender and age. A systematic review and meta-analysis of observational studies estimating CKD prevalence in general populations was conducted through literature searches in 8 databases. We assessed pooled data using a random effects model. Of 5,842 potential articles, 100 studies of diverse quality were included, comprising 6,908,440 patients. Global mean(95%CI) CKD prevalence of 5 stages 13.4%(11.7-15.1%), and stages 3-5 was 10.6%(9.2-12.2%). Weighting by study quality did not affect prevalence estimates. CKD prevalence by stage was Stage-1 (eGFR>90+ACR>30): 3.5% (2.8-4.2%); Stage-2 (eGFR 60-89+ACR>30): 3.9% (2.7-5.3%); Stage-3 (eGFR 30-59): 7.6% (6.4-8.9%); Stage-4 = (eGFR 29-15): 0.4% (0.3-0.5%); and Stage-5 (eGFR<15): 0.1% (0.1-0.1%). CKD has a high global prevalence with a consistent estimated global CKD prevalence of between 11 to 13% with the majority stage 3. Future research should evaluate intervention strategies deliverable at scale to delay the progression of CKD and improve CVD outcomes. PMID- 27383072 TI - International Conference on Fresh-Cut Produce. PMID- 27383073 TI - Does Fear of Terrorism Differ From Fear of Crime and Sexual Assault: A Question of Geographical Location and Residential Area. AB - The study describes an examination of three types of fear: crime, sexual assault, and terrorism. The sample consisted of 507 adults from three different geographical locations in Israel with different levels of crime and terror attacks. With regard to fear of crime and fear of sexual assault, the results were compatible with the findings of many studies that indicate the effect of residential area features on levels of fear. Fear of terrorism was found to be more complex. The theoretical framework used to assess fear of crime is not fully suitable for assessing and examining fear of terrorism. Other variables should be taken into consideration, such as religion and ideology. PMID- 27383074 TI - New functional and biophysical insights into the mitochondrial Rieske iron-sulfur protein from genetic suppressor analysis in C. elegans. AB - Several intragenic mutations suppress the C. elegans isp-1(qm150) allele of the mitochondrial Rieske iron-sulfur protein (ISP), a catalytic subunit of Complex III of the respiratory chain. These mutations were located in a helical region of the "tether" span of ISP-1, distant from the primary mutation in the extrinsic head, and suppressed all pleiotropic phenotypes associated with the qm150 allele. Analysis of these suppressors revealed control of electron transfer into Complex III through a "spring-loaded" mechanism involving a binding force for formation of enzyme-substrate complex, counter balanced by forces (a chemical "spring") favoring helix formation in the tether. The primary P->S mutation results in inhibition of electron flow into the Q-cycle by decreasing the binding force, and the tether mutations relieve this inhibition by weakening the "spring." In this commentary we discuss additional control features, and relate the primary inhibition to outcomes at the organismal level. In particular, the sensitivity to hyperoxia and the elevated reactive oxygen species (ROS) seen in isp-1(qm150), likely reflect over-reduction of the quinone pool, which is upstream of the inhibited site; at high O2, this would lead to increased ROS production through complex I. We speculate that alternative NADH:ubiquinone oxidoreductase activity in C. elegans from the worm apoptosis inducing factor (AIF) homolog (WAH-1) might also be involved, and that WAH-1 might have a "canary" function in detection of this adverse state (high O2/reduced pool), and a role in protection of the organism by transformation to AIF-like products, and apoptotic recycling of defective cells. PMID- 27383075 TI - Ann Ward. PMID- 27383076 TI - Interventional cardiology: Polymer-free drug-eluting stents - a safe and effective option for ACS. PMID- 27383077 TI - Atrial fibrillation: Puzzling out the race paradox. PMID- 27383078 TI - Management of survivors of cardiac arrest - the importance of genetic investigation. AB - Management of survivors of cardiac arrest is largely based on a traditional approach. However, during the past decade, arrhythmias of genetic origin have increasingly been recognized as contributing to many more cases than previously appreciated. This realization is forcing physicians managing the survivors of cardiac arrest also to consider family members. In this Perspectives article, we examine the appropriate management approaches for survivors of cardiac arrests related to channelopathies, cardiomyopathies, or ischaemic heart disease, and for their families. Important implications for families of individuals who have experienced sudden cardiac death as part of sudden infant death syndrome or during sport activity are also discussed. Congenital long QT syndrome provides a paradigm of the logical sequence of the steps that should be performed. When a diagnosis of the cause of the cardiac arrest is certain or probable, every effort should be made to identify the genetic basis of disease, because this approach will enable the identification and early protection of similarly affected family members. Accordingly, the availability in hospitals of at least one cardiologist with cardiovascular genetics expertise would improve the management of survivors of cardiac arrest as well as of their families. PMID- 27383079 TI - Stroke risk assessment in atrial fibrillation: risk factors and markers of atrial myopathy. AB - Atrial fibrillation (AF) is a complex phenomenon associated with electrical, mechanical, and structural abnormalities of the atria. Ischaemic stroke in AF is only partially understood, but the mechanisms are known to be related to the atrial substrate as well as the atrial rhythm. The temporal dissociation between timing of AF and occurrence of stroke has led to the hypothesis that fibrotic, prothrombotic atrial tissue is an important cause of thrombus formation in patients with AF, independent of the atrial rhythm. Current stroke risk scores are practical, but limited in their capacity to predict stroke risk accurately in individual patients. Stroke prediction might be improved by the addition of emerging risk factors, many of which are expressions of atrial fibrosis. The use of novel parameters, including clinical criteria, biomarkers, and imaging data, might improve stroke risk prediction and inform on optimal treatment for patients with AF and perhaps individuals only at risk of AF. PMID- 27383082 TI - A little more learning: A re-analysis of ignorance-driven inference in Frosch, Beaman, & McCloy (2007). PMID- 27383081 TI - Risk factors: Evolving epidemiology of sodium intake and CVD. PMID- 27383083 TI - Physiological Significance of Well-tolerated Inspiratory Pressure to Chronic Obstructive Pulmonary Disease Patient with Hypercapnia During Noninvasive Pressure Support Ventilation. AB - The inspiratory pressure is often set by tolerance of chronic obstructive pulmonary disease (COPD) patient during noninvasive pressure support ventilation (PSV). However, physiological effects of this setting remain unclear. This study was undertaken to assess the physiological effect of highest tolerated assist level on COPD patient. The baseline inspiratory pressure (PS) was titrated by tolerance in 15 severe COPD patients with hypercapnia during acute exacerbation. In addition to the baseline PS, an additional decrease by 25% (PS- = 75% PS) or increase by 25% (PS+ = 125% PS) of PS was applied to the patients. Each level lasted at least 20 minutes. Respiratory rate (RR), tidal volume (Vt), inspiratory effort (PTPpesin/min), and neuro-ventilatory coupling (VE/RMS%) were measured. Asynchrony Index (AI) was calculated. The Vt and VE/RMS% were significantly increased by PS level (Vt: 561 +/- 102 ml, VE/RMS%: 1.06 +/- 0.42 L/%, comfort score: 7.5 +/- 1.1). The inspiratory muscles were sufficiently unloaded (PTPpesin/min 56.67 +/- 32.71 cmH2O.S/min). In comparison with PS, PS+ resulted in a further increase in Vt, VE/RMS% and AI (P < 0.01), with no further reduction in neural drive (RMS) and respiratory muscle activity (P > 0.05). Increasing inspiratory pressure significantly enhances the VE/RMS% and Vt. However, the inspiratory pressure higher than COPD patient's most tolerated level cannot lead to further reduction in respiratory muscle load and RMS, but more asynchrony events. Physiological data can monitor the patient's responses and the ventilator patient interaction, which may provide objective criterion to ventilator setting. PMID- 27383084 TI - Indigenous youth-developed self-assessment: The Personal Balance Tool. AB - The Fresno American Indian Health Project (FAIHP) Youth Council developed and pilot tested a strength-based, holistic, and youth-friendly self-assessment tool grounded in the Medicine Wheel, a framework and theoretical orientation for teaching wellness in many tribal communities. This paper summarizes the development of the Youth Personal Balance Tool and the methods used for tool revisions through two separate pilot studies and ongoing process evaluations across 3 years. Using a community-based participatory evaluation model, FAIHP leveraged community resources to implement an annual youth Gathering of Native Americans to support youth in healing from historical and intergenerational trauma and restoring communities to balance by making them a part of the solution. This tool is one of many outcomes of their work. The Youth Council is offering the tool as a gift (in line with the cultural value of generosity) to other Indigenous communities that are searching for culturally competent self assessment tools for youth. The authors believe this tool has the potential to progress the field in strength-based, holistic, youth-friendly assessment as a culturally competent method for Indigenous evaluation and research. PMID- 27383080 TI - Nutraceutical therapies for atherosclerosis. AB - Atherosclerosis is a chronic inflammatory disease affecting large and medium arteries and is considered to be a major underlying cause of cardiovascular disease (CVD). Although the development of pharmacotherapies to treat CVD has contributed to a decline in cardiac mortality in the past few decades, CVD is estimated to be the cause of one-third of deaths globally. Nutraceuticals are natural nutritional compounds that are beneficial for the prevention or treatment of disease and, therefore, are a possible therapeutic avenue for the treatment of atherosclerosis. The purpose of this Review is to highlight potential nutraceuticals for use as antiatherogenic therapies with evidence from in vitro and in vivo studies. Furthermore, the current evidence from observational and randomized clinical studies into the role of nutraceuticals in preventing atherosclerosis in humans will also be discussed. PMID- 27383086 TI - The intersection of software and strengths: Using internet technology and case management software to assist Strength-Based Practice. AB - The focus of this investigation is the helping professionals working within American Indian and Alaska Native (AI/AN) communities. This article looks at how innovative technology-in the form of automated case management software and Internet connectivity-can assist effective implementation of Strength-based Practice and agency services within tribal courts and the many other helping agencies that serve AI/AN populations. We seek to expand practice knowledge by reviewing the benefits that this software and Internet connectivity can offer to agency operations and exploring how they can assist case management services. PMID- 27383085 TI - Women finding the way: American Indian women leading intervention research in Native communities. AB - Although there is literature concentrating on cross-cultural approaches to academic and community partnerships with Native communities, few address the process and experiences of American Indian women leading federally funded and culturally grounded behavioral health intervention research in Native communities. This paper summarizes relevant literature on community-engaged research with Native communities, examines traditional roles and modern challenges for American Indian women, describes the culturally grounded collaborative process for the authors' behavioral health intervention development with Native communities, and considers emergent themes from our own research experiences navigating competing demands from mainstream and Native communities. It concludes with recommendations for supporting and enhancing resilience. PMID- 27383087 TI - In their own words: Success stories from The Great Lakes Native American Research Center for Health. AB - In 2009, the Great Lakes Native American Research Center for Health (GLNARCH) set out to generate a promotional video that highlights the successes of the program. Ten GLNARCH interns were interviewed and filmed for participation in the promotional video using a documentary production style. During the editing and transcription process, interviewer responses were noted for relevance to theoretical frameworks--specifically, tribal critical race theory, mentoring, and cultural compatibility--which guided GLNARCH program design. Quotations were transcribed to illustrate these themes. Though the interviews were not intended as a formal qualitative analysis, powerful narratives that are relevant to participatory research emerged. The emergence of narratives that align with relevant theoretical frameworks suggests a novel methodology for a culturally responsive, participatory reporting system. PMID- 27383088 TI - Ego strengths, racial/ethnic identity, and well-being among North American Indian/First Nations adolescents. AB - This study investigated associations between ego strengths (psychosocial development), racial/ethnic identity using Multi-Ethnic Identity Measure-Revised (exploration, commitment) and Multidimensional Measure of Racial Identity (centrality, private regard, public regard) dimensions, and personal adjustment/well-being among 178 North American Indian/First Nations adolescents who resided and attended school on reserves. As predicted, ego strengths related directly with centrality, private regard, and the adjustment measures; the moderation of ego strengths for exploration, commitment, and private regard reflected adverse functioning for those with less than advanced ego strengths. As well, ego strengths mediated associations between centrality and private regard with several measures of personal well-being. Practical and theoretical implications are considered. PMID- 27383089 TI - American Indian Elders' resilience: Sources of strength for building a healthy future for youth. AB - This study examined American Indian (AI) elders' resilience to support an intervention to build resilience among AI urban youth. A literature review of peer-reviewed articles that address resilience in AI and other Indigenous elders yielded six studies that focused on intergenerational relationships, culture, and self-identity. In addition, a qualitative research project collected narratives with urban AI elders to document perceptions of resilience and resilience strategies. The combined outcomes of the literature search and research project revealed how resilience is exemplified in elders' lives and how resilience strategies are linked to cultural teachings and values, youth activities, and education. PMID- 27383090 TI - American Indian and Alaska Native resilience along the life course and across generations: A literature review. AB - Examining American Indian and Alaska Native (AI/AN) resilience using the life course framework could inform public health strategies that support favorable health outcomes, despite adversity (e.g., discrimination, historical loss, comorbidity). A systematic review of peer-reviewed literature published from 1970 to 2015 yielded eight articles on AI/AN life course and resilience. A content analysis identified three themes. AI/AN resilience is 1) an ongoing, dynamic process, 2) evident within linked lives and life transitions, and 3) accessed through cultural knowledge and practice. Resilience research could change the paradigm of AI/AN health research to guide asset-based approaches across the life course. PMID- 27383091 TI - Native Transformations in the Pacific Northwest: A strength-based model of protection against substance use disorder. AB - This paper presents findings from the Native Transformations Project, an exploratory community-based participatory research study that aims to identify sources of strength and protection against substance use disorder in three tribal communities in the coastal Pacific Northwest. Preliminary results from the study describe the specific settings, acts, and behaviors that build strengths and provide protection at the family, community, individual, and spiritual levels within coastal Pacific Northwest local tribal cultures. Findings from this study give voice to stated community preferences for grassroots Native intervention programs based in local cultural knowledge, worldviews, values, and theories of change, that operate at the local level on their own terms. PMID- 27383092 TI - Partnering with American Indian communities in strength-based collaborative health research: Guiding principles from the Fort Peck Ceremony of ResearchProject. AB - BACKGROUND: The Ceremony of Research Project was implemented to strengthen tribal communities' ability to harmonize Western research processes with Indigenous ways of knowing. METHODS: Focus groups were conducted with tribal members to understand Indigenous processes, beliefs, and practices necessary to promote positive research experiences with tribal communities. RESULTS: Findings address time; relationship building and maintenance; inclusion of diverse tribal members in the research design, as well as American Indian epistemology; respect for tribal values, beliefs, and customs throughout the research process; and the reciprocity of research. CONCLUSIONS: Our study has important implications for how researchers can take a strengthbased approach to conducting research with tribal communities. PMID- 27383093 TI - Strength-based well-being indicators for Indigenous children and families: A literature review of Indigenous communities' identified well-being indicators. AB - Mainstream child and family well-being indicators frequently are based on measuring health, economic, and social deficits, and do not reflect Indigenous holistic and strength-based definitions of health and well-being. The present article is a review of literature that features Indigenous communities' self identified strength-based indicators of child and family well-being. The literature search included Indigenous communities from across the world, incorporating findings from American Indians and Alaska Natives, First Nations, Native Hawaiians, Maori, Aboriginal Australians, and Sami communities. Sorting the identified indicators into the quadrants of the Relational Worldview, an Indigenous framework for well-being based on medicine wheel teachings that views health and well-being as a balance among physical, mental, contextual, and spiritual factors, the authors discuss the findings. PMID- 27383094 TI - Perceptions and use of community- and school-based behavioral health services among urban American Indian/Alaska Native youth and families. AB - Understanding youths' awareness and use of behavioral health services is important for improving services and engagement. Interviews and focus groups were conducted with students, parents, and teachers/staff in an urban area to understand awareness and use of a school's Native-tailored and -staffed school based behavioral health center (NT-BHC) and community-based services. Results showed overwhelmingly positive responses regarding NT-BHC staff and services, with concerns focused on too few staff and services, and on privacy and confidentiality, as well as important differences in awareness and use of behavioral health services among youth, parents, and teachers/staff, valuable for improving engagement with and services for AI/AN youth. PMID- 27383095 TI - Entrepreneurship education: A strength-based approach to substance use and suicide prevention for American Indian adolescents. AB - American Indian (AI) adolescents suffer the largest disparities in substance use and suicide. Predominating prevention models focus primarily on risk and utilize deficit-based approaches. The fields of substance use and suicide prevention research urge for positive youth development frameworks that are strength based and target change at individual and community levels. Entrepreneurship education is an innovative approach that reflects the gap in available programs. This paper describes the development and evaluation of a youth entrepreneurship education program in partnership with one AI community. We detail the curriculum, process evaluation results, and the randomized controlled trial evaluating its efficacy for increasing protective factors. Lessons learned may be applicable to other AI communities. PMID- 27383096 TI - Culturally sensitive assessments as a strength-based approach to wellness in Native communities: A community-based participatory research project. AB - American Indians and Alaska Natives (AI/ANs) have a unique, traumatic, and alienating history of education in the U.S., which may be directly related to overall health and well-being. Community engagement is critical in well-being research with Native communities, especially when investigating culturally sensitive topics, such as early education experiences. This study investigates the value of a community-based participatory research approach in gaining valuable culturally sensitive information from Native people in a respectful manner. Assessment participation and feedback are analyzed and presented as indicators of Native participant engagement success in a potentially sensitive research project exploring early education experiences. PMID- 27383097 TI - Introduction. PMID- 27383098 TI - Changing nomenclature for PBC from "Primary Biliary Cirrhosis" to "Primary Biliary Cholangitis". PMID- 27383099 TI - Prevention of colorectal cancer. PMID- 27383100 TI - Colorectal cancer prevention and early diagnosis using endoscopy. PMID- 27383101 TI - Where the colorectal cancer chemoprevention is and where it is going. PMID- 27383102 TI - Colorectal cancer prevention of familial adenomatous polyposis. PMID- 27383103 TI - [Not Available]. PMID- 27383104 TI - The clinical importance of "bamboo joint-like appearance" on upper gastrointestinal endoscopy for the diagnosis of Crohn's disease. AB - Upper gastrointestinal (GI) lesions are frequently reported in Crohn's disease, in which the entire GI tract is affected. In these cases, erosive fissures regularly transversing folds that are longitudinally aligned along the lesser curvature of the gastric body and cardia are described as having a "bamboo joint like appearance". We designed a blinded experiment in which upper GI imaging without a final diagnosis was checked by three observers to determine the usefulness of the bamboo joint-like appearance in the diagnosis of Crohn's disease. For the three observers, sensitivities of appearance were 30.5%, 56.9%, and 51.4%, while specificities were 99.6%, 98.5%, and 99.3%. Thus, the bamboo joint-like appearance was not useful for the identification of Crohn's disease patients. Nevertheless, patients exhibiting the bamboo joint-like appearance in upper GI imaging should undergo further examination due to the high probability of Crohn's disease. PMID- 27383105 TI - Lanthanum phosphate deposition in the gastric mucosa of patients with chronic renal failure. AB - A 77-year-old Japanese man underwent endoscopic submucosal dissection twice over a 5-year period for the treatment of two separate early gastric cancers. He had been taking lanthanum carbonate, an orally administered phosphate binder, for 3 years. Esophagogastroduodenoscopy revealed reddish mucosa in the greater curvature and anterior wall of the gastric angle, while granular, white deposits were also observed in some areas of this reddish mucosa. Additionally, biopsy specimens from the gastric mucosa revealed the deposition of fine, amorphous, eosinophilic material, which appeared bright on scanning electron microscopy. Energy dispersive X-ray spectroscopy revealed the presence of lanthanum and phosphate in these bright areas, and elemental mapping confirmed that their distribution was identical to that seen in the bright areas. Based on these findings, the diagnosis of lanthanum phosphate deposition in the gastric mucosa was determined. PMID- 27383106 TI - A case of pancreatic arteriovenous malformation identified by investigating the cause of upper abdominal pain associated with acute pancreatitis. AB - A man in his 60s with epigastric pain was diagnosed with acute pancreatitis and subsequently recovered following conservative treatment. However, because of repeated upper abdominal pain and the formation of a pancreatic pseudocyst, he was transferred to our institution for evaluation. Dynamic computed tomography (CT) scanning confirmed abnormal vessels in the tail of the pancreas and early venous return to the splenic vein in the early arterial phase. Abdominal angiography revealed a racemose vascular network in the tail of the pancreas, confirming the presence of an arteriovenous malformation (AVM) in this region. This AVM was thought to be the cause of the acute pancreatitis, so a distal pancreatectomy was performed. The patient's postoperative course was uneventful, and there has been no recurrence at the 7-month postoperative follow-up. Surgical resection has a low recurrence rate and good outcome;thus, if a pancreatic AVM appears difficult to treat with conservative medical therapy, surgical resection appears to be the definitive treatment. PMID- 27383107 TI - A case of a solitary Mycobacterium avium complex lesion of the liver. AB - A 70-year-old woman was admitted to our hospital on suspicion of liver tumor on regular abdominal ultrasonography. The abdominal ultrasonography identified a solitary, low-echoic lesion measuring 17mm in diameter in S7. This lesion was not enhanced in any phase of contrast-enhanced computed tomography (CT), and thus we performed a liver biopsy. Histopathological examination revealed a caseating granuloma. The chest CT showed pulmonary nodules, and Mycobacterium intracellulare was cultured from the bronchoalveolar lavage fluid. We diagnosed the individual with a Mycobacterium avium complex infection, and suspected that this was the cause of the solitary liver lesion. PMID- 27383108 TI - A case of intraductal papillary neoplasm of the bile duct preoperatively diagnosed using contrast-enhanced endoscopic ultrasonography. AB - A 71-year-old man was referred to our hospital and was diagnosed with jaundice and a liver function disorder. Although we suspected an intraductal papillary neoplasm of the bile duct (IPNB)-derived caudate branches on the basis of contrast-enhanced CT, MRI, and endoscopic retrograde cholangiopancreatography, we could not clearly identify the tumor. Therefore, we examined the lesion using endoscopic ultrasonography (EUS). We could visualize an iso-hyperechoic elevated tumor in the caudate branches. The tumor was observed as a hypervascular lesion using contrast-enhanced EUS, which is useful in preoperatively diagnosing IPNB and detecting the presence of lesions. PMID- 27383109 TI - A refractory duodenal ulcer with a biliary-duodenal fistula following the administration of bevacizumab. AB - A 65-year-old woman with recurrent breast cancer was repeatedly treated with bevacizumab, an anti-VEGF antibody. In addition, she was also frequently prescribed a nonsteroidal anti-inflammatory drug for abdominal pain. Melena was revealed 2 months after the final treatment with bevacizumab, and an endoscopic study revealed a duodenal ulcer (DU) that was resistant to anti-ulcer therapy. A cholangiography identified a biliary-duodenal fistula with bile juice leaking from the ulcer base. Therefore, a biliary stent was placed into the common bile duct for 3 months until the DU healed. This is the first case of a refractory DU with a biliary-duodenal fistula in a patient treated with bevacizumab. PMID- 27383110 TI - A case of cutaneous tuberculosis: a clue to diagnosing miliary tuberculosis. PMID- 27383113 TI - Ambient Light Exposure and Changes in Obesity Parameters: A Longitudinal Study of the HEIJO-KYO Cohort. AB - CONTEXT: Previous epidemiological studies have suggested an association between nighttime light levels and the prevalence of obesity, although evidence is limited to cross-sectional studies. OBJECTIVE: To evaluate the longitudinal association between ambient light exposure and the subsequent changes in obesity parameters. DESIGN AND PARTICIPANTS: Data from 1110 elderly participants at baseline (mean age, 71.9 years) and data from 766 at follow-up (median, 21 months) were included in this prospective population-based study. MEASURES: Time dependent ambient light exposure based on objective measurements and changes in the waist-to-height ratio (WHtR) and body mass index (BMI) were measured. RESULTS: Multivariable mixed-effect linear regression models showed a significant association between light exposure and the %WHtR gain; this was independent of potential confounders (eg, caloric intake, physical activity, and sleep/wake parameters). Nighttime or evening exposure to higher light intensity was significantly associated with subsequent %WHtR gain. Morning exposure to a longer time >=500 lux or nighttime exposure to a longer time <3 lux was significantly associated with subsequent %WHtR loss. These association trends were nearly consistent when the BMI was used as an obesity parameter. Increased nighttime light exposure (mean >=3 vs <3 lux) was estimated to correspond to a 10.2% WHtR gain and a 10.0% increase in BMI over 10 years. CONCLUSIONS: Ambient light exposure, such as increased nighttime or evening light exposure and decreased morning light exposure, was independently associated with subsequent increases in obesity parameters. Further interventional studies are warranted to establish an optimal controlled lighting environment as a preventive option against obesity. PMID- 27383112 TI - Thyroid Hormone Status in Umbilical Cord Serum Is Positively Associated with Male Anogenital Distance. AB - CONTEXT: In human adults and adolescents, thyroid function affects sex hormones and male reproductive functions. Little is known about the thyroid function effects on the gonadal development in human infants. OBJECTIVE: The aim was to examine the association between thyroid hormones (THs) and sexually dimorphic genital development or fetal growth. DESIGN: This is a birth cohort study. PARTICIPANTS: A total of 616 mothers and newborns were analyzed from two local hospitals. MAIN OUTCOME MEASURES: TSH, free T3 (FT3), and free T4 (FT4) levels in cord blood serum, anogenital distance (AGD), birth weight, birth length, birth body mass index, and head circumference in neonates. RESULTS: Longer AGD in male newborns was observed with higher cord serum FT3 (beta, 1.36 mm [95% confidence interval (CI), 0.58-2.13] for 1 pmol/L FT3), FT4 (beta, 0.12 mm [95% CI, 0.00 0.25] for 1 pmol/L FT4), and TSH (beta, 3.14 mm [95% CI, 0.65-5.63] for a 10-fold TSH increase), and with a lower FT4/FT3 ratio (beta, -0.11 mm [95% CI, -0.20 to 0.02] for doubling FT4/FT3 ratio). The relationships between TSH, birth weight, and birth length were different by secondhand smoke exposure. Secondhand smoke exposure had an effect modification, with interaction P value .039 and .010, respectively. Secondhand smoke exposure also had an effect modification on the relation between FT4 and head circumference with interaction P value .020. CONCLUSIONS: In the absence of overt thyroid dysfunction, THs are positively associated with AGD in male newborns. TH effects on body size and head circumference may be modified by maternal secondhand smoke exposure. PMID- 27383114 TI - Excessive Age-Related Decline in Functional Ovarian Reserve in Infertile Women: Prospective Cohort of 15,500 Women. AB - CONTEXT: Whether infertile women exhibit accelerated ovarian aging and whether a low ovarian reserve is overrepresented in infertility populations is not known. OBJECTIVE: To compare the age-related decline in antral follicle count (AFC), a biomarker of the ovarian reserve, in fertile and infertile women. DESIGN: Cross sectional data from a large prospective cohort study conducted from January 2013 to December 2014. SETTING: Thirteen fertility centers across Spain. PATIENTS OR OTHER PARTICIPANTS: Consecutive women aged 18 to 45 years of age attending the fertility centers either seeking fertility treatment or as fertile women wishing to act as potential oocyte donors. INTERVENTION(S): Standardized AFC assessment on day 2 to 4 of the cycle. MAIN OUTCOME MEASURE(S): Age-related decline of AFC for both fertile and infertile women. RESULTS: A total of 15 500 women, of whom 5722 were potential donors and 9778 were patients seeking fertility treatment, participated in the study. Average AFC was greater in potential oocyte donors than in infertile women (20 [interquartile range, 16-24] vs 10 [interquartile range, 6-15], respectively; P < .001), a difference that was maintained after adjustment for age (P < .001) in a model predicting log(AFC) from donor vs infertility, adjusting for 2-year age bands. The age-related decline in AFC was much steeper in infertile women compared with that of potential oocyte donors, with an increased prevalence of a low ovarian reserve (AFC < 5) at all ages in infertile women. CONCLUSIONS: The age-related decline in AFC was substantially greater in infertility patients than potential oocyte donors. Overrepresentation in infertility populations of women with low ovarian reserve may be an additional functional cause of infertility. PMID- 27383116 TI - Relation Between Insulin Sensitivity and Metabolic Abnormalities in Japanese Men With BMI of 23-25 kg/m2. AB - CONTEXT: Although metabolic abnormalities are often developed in Asians with body mass index (BMI) of 23-25 kg/m2, the characteristics of the nonobese Asians with metabolic abnormality have not been fully understood. OBJECTIVE: The aim of this study was to investigate the clinical significance of insulin sensitivity in Japanese men with BMI of 23-25 kg/m2. DESIGN AND PARTICIPANTS: In this study, we defined hypertension, hyperglycemia, and dyslipidemia as cardiometabolic risk factors (CMRFs). We recruited subjects who met the following selection criteria: men with BMI of 21-23 kg/m2 and no CMRF (n = 24); men with BMI of 23-25 kg/m2 and no CMRF (n = 28), or one CMRF (n = 28), or at least two CMRFs (n = 14); and overweight men with metabolic syndrome (n = 20). Insulin sensitivity (IS) and ectopic fat content in muscle and liver were measured by two-step hyperinsulinemic-euglycemic clamp and 1H-magnetic resonance spectroscopy, respectively. RESULTS: Among subjects with BMI of 23-25 kg/m2, impaired IS in muscle, but not in liver, was found in those with even one CMRF, whereas impaired IS in both muscle and liver was observed in overweight men with metabolic syndrome. Liver fat accumulation and elevated liver enzymes were associated with impaired IS in both muscle and liver in those subjects. CONCLUSIONS: Among Japanese men with BMI of 23-25 kg/m2, muscle insulin resistance was present in those with even one CMRF. In this population, liver fat accumulation and/or elevated liver enzymes could be a good marker for impaired IS in both muscle and liver. PMID- 27383115 TI - Non-Lethal Type VIII Osteogenesis Imperfecta Has Elevated Bone Matrix Mineralization. AB - CONTEXT: Type VIII osteogenesis imperfecta (OI; OMIM 601915) is a recessive form of lethal or severe OI caused by null mutations in P3H1, which encodes prolyl 3 hydroxylase 1. OBJECTIVES: Clinical and bone material description of non-lethal type VIII OI. DESIGN: Natural history study of type VIII OI. SETTING: Pediatric academic research centers. PATIENTS: Five patients with non-lethal type VIII OI, and one patient with lethal type VIII OI. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Clinical examinations included bone mineral density, radiographs, and serum and urinary metabolites. Bone biopsy samples were analyzed for histomorphometry and bone mineral density distribution by quantitative backscattered electron imaging microscopy. Collagen biochemistry was examined by mass spectrometry, and collagen fibrils were examined by transmission electron microscopy. RESULTS: Type VIII OI patients have extreme growth deficiency, an L1 L4 areal bone mineral density Z-score of -5 to -6, and normal bone formation markers. Collagen from bone and skin tissue and cultured osteoblasts and fibroblasts have nearly absent 3-hydroxylation (1-4%). Collagen fibrils showed abnormal diameters and irregular borders. Bone histomorphometry revealed decreased cortical width and very thin trabeculae with patches of increased osteoid, although the overall osteoid surface was normal. Quantitative backscattered electron imaging showed increased matrix mineralization of cortical and trabecular bone, typical of other OI types. However, the proportion of bone with low mineralization was increased in type VIII OI bone, compared to type VII OI. CONCLUSIONS: P3H1 is the unique enzyme responsible for collagen 3 hydroxylation in skin and bone. Bone from non-lethal type VIII OI children is similar to type VII, especially bone matrix hypermineralization, but it has distinctive features including extremely thin trabeculae, focal osteoid accumulation, and an increased proportion of low mineralized bone. PMID- 27383117 TI - Interpersonal Mechanisms Explaining the Transfer of Well- and Ill-Being in Coach Athlete Dyads. AB - The current study explored coaches' interpersonal behaviors as a mechanism for well- and ill-being contagion from coach to athlete and vice versa. Eighty-two coach-athlete dyads from individual sports completed selfreport measures before and after a training session. Structural equation modeling supported three actor partner interdependence mediation models, in which coaches' presession well- and ill-being were associated with changes in athletes' well- and ill-being over the course of the session. These relationships were mediated by athletes' perceptions of their coaches' interpersonal styles during the session. The reciprocal transfer from athlete to coach was not fully supported. Nonetheless, coaches' perceptions of their own interpersonal behaviors were associated with changes in their postsession well- and ill-being. Overall, evidence is provided for the contagion of affect from authority figures to those under their instruction but not vice versa. PMID- 27383118 TI - The role of interconnectivity in control of an Ebola epidemic. AB - Several West African countries - Liberia, Sierra Leone and Guinea - experienced significant morbidity and mortality during the largest Ebola epidemic to date, from late 2013 through 2015. The extent of the epidemic was fueled by outbreaks in large urban population centers as well as movement of the pathogen between populations. During the epidemic there was no known vaccine or drug, so effective disease control required coordinated efforts that include both standard medical and community practices such as hospitalization, quarantine and safe burials. Due to the high connectivity of the region, control of the epidemic not only depended on internal strategies but also was impacted by neighboring countries. In this paper, we use a deterministic framework to examine the role of movement between two populations in the overall success of practices designed to minimize the extent of Ebola epidemics. We find that it is possible for even small amounts of intermixing between populations to positively impact the control of an epidemic on a more global scale. PMID- 27383119 TI - Meta-analysis of the efficacy of proton pump inhibitors for the symptoms of laryngopharyngeal reflux. AB - The objective of this study was to perform a systematic review and meta-analysis to assess the effectiveness of proton pump inhibitors (PPI) for reflux disease in adult patients with laryngopharyngeal symptoms. A comprehensive search of Cochrane Library, EMBASE, Ovid EBM Reviews, and PubMed was performed for English language literature about laryngopharyngeal reflux (LPR), in September 2014. The papers were filtered using pre-defined inclusion and exclusion criteria. Eight papers were identified and included in this meta-analysis. The sample comprised a pooled total of 370 patients, of which 210 and 160 patients took PPIs and placebo, respectively. The difference between PPIs and placebo groups in overall improvement of symptoms in adult patients with LPR was not statistically significant (RR=1.22; 95%CI=0.93-1.58; P=0.149). The difference in cough improvement was also not significant between PPIs and placebo groups (RR=0.65; 95%CI=0.30-1.41; P=0.279). PMID- 27383120 TI - Low vaspin levels are related to endothelial dysfunction in patients with ankylosing spondylitis. AB - Vaspin is a novel adipocytokine associated with glucose tolerance and chronic inflammation. Some studies reveal that vaspin may be involved in cardiovascular diseases. Our objective was to investigate the relationship between serum vaspin levels and endothelial function in patients with ankylosing spondylitis. One hundred and twenty patients with newly diagnosed ankylosing spondylitis and 100 healthy subjects were studied. Serum vaspin levels were measured with enzyme linked immunosorbent assay. High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia (flow-mediated dilation, FMD) and after sublingual glyceryltrinitrate. Serum vaspin level in patients was 1.92+/-1.03 ng/mL, which was significantly lower than that in healthy subjects (2.88+/-0.81 ng/mL). By dividing the distribution of serum vaspin levels into quartiles, FMD levels increased gradually with the increase of serum vaspin levels in patients (P<0.01). Univariate analysis showed a correlation between vaspin and FMD (r=0.73, P=0.003), low-density lipoprotein cholesterol (r=-0.45, P=0.033), high-density lipoprotein cholesterol (r=0.63, P=0.025), fasting blood glucose (r=-0.79, P=0.006), triglycerides (TG) (r=-0.68, P=0.036), systolic blood pressure (r=-0.35, P=0.021), C-reactive protein (r= 0.67, P=0.011), homeostatic model assessment of insulin resistance (HOMA-IR) (r= 0.77, P=0.023) and erythrocyte sedimentation rate (r=-0.88, P=0.039) in patients. Multivariate analysis indicated that serum vaspin levels were independently associated with FMD, HOMA-IR and TG in patients. Our study found that serum vaspin levels were decreased in patients with ankylosing spondylitis and were associated with FMD levels. Vaspin may serve as an independent marker for detecting early stage atherosclerosis in patients with ankylosing spondylitis. PMID- 27383121 TI - Effect of magnesium ion on human osteoblast activity. AB - Magnesium, a promising biodegradable metal, has been reported in several studies to increase bone formation. Although there is some information regarding the concentrations of magnesium ions that affect bone remodeling at a cellular level, little is known about the effect of magnesium ions on cell gap junctions. Therefore, this study aimed to systematically investigate the effects of different concentrations of magnesium on bone cells, and further evaluate its effect on gap junctions of osteoblasts. Cultures of normal human osteoblasts were treated with magnesium ions at concentrations of 1, 2 and 3 mM, for 24, 48 and 72 h. The effects of magnesium ions on viability and function of normal human osteoblasts and on gap junction intercellular communication (GJIC) in osteoblasts were investigated. Magnesium ions induced significant (P<0.05) increases in cell viability, alkaline phosphate activity and osteocalcin levels of human osteoblasts. These stimulatory actions were positively associated with the concentration of magnesium and the time of exposure. Furthermore, the GJIC of osteoblasts was significantly promoted by magnesium ions. In conclusion, this study demonstrated that magnesium ions induced the activity of osteoblasts by enhancing GJIC between cells, and influenced bone formation. These findings may contribute to a better understanding of the influence of magnesium on bone remodeling and to the advance of its application in clinical practice. PMID- 27383122 TI - Role of adenylyl cyclase in reduced beta-adrenoceptor-mediated vasorelaxation during maturation. AB - Beta-adrenergic receptor (betaAR)-dependent blood vessel relaxation is impaired in older animals and G protein activation has been suggested as the causative mechanism. Here, we investigated the role of betaAR subtypes (beta1AR, beta2AR, and beta3AR) and cAMP in maturation-dependent vasorelaxation impairment. Aortic rings from 15 Sprague-Dawley male rats (3 or 9 weeks old) were harvested and left intact or denuded of the endothelium. Vascular relaxation in aortic rings from younger and older groups was compared in the presence of betaAR subtype agonists and antagonists along with cAMP and cGMP antagonists. Isolated aortic rings were used to evaluate relaxation responses, protein expression was evaluated by western blot or real time PCR, and metabolites were measured by ELISA. Expression of betaAR subtypes and adenylyl cyclase was assessed, and cAMP activity was measured in vascular tissue from both groups. Isoproterenol- and BRL744-dependent relaxation in aortic rings with and without endothelium from 9-week-old rats was impaired compared with younger rats. The beta1AR antagonist CGP20712A (10-7 M) did not affect isoproterenol or BRL744-dependent relaxation in arteries from either group. The beta2AR antagonist ICI-118,551 (10-7 M) inhibited isoproterenol dependent aortic relaxation in both groups. The beta3AR antagonist SR59230A (10-7 M) inhibited isoproterenol- and BRL744-dependent aortic ring relaxation in younger but not in older rats. All betaAR subtypes were expressed in both groups, although beta3AR expression was lower in the older group. Adenylyl cyclase (SQ 22536) or protein kinase A (H89) inhibitors prevented isoproterenol-induced relaxation in younger but not in older rats. Production of cAMP was reduced in the older group. Adenylyl cyclase III and RyR3 protein expression was higher in the younger group. In conclusion, altered expression of beta3AR and adenylyl cyclase III may be responsible for reduced cAMP production in the older group. PMID- 27383123 TI - Macelignan inhibits bee pathogenic fungi Ascophaera apis growth through HOG1 pathway. AB - Ascosphaera apis is a bee pathogen that causes bee larvae infection disease, to which treatment is not yet well investigated. The aim of this study was to investigate antifungal susceptibility in vitro against A. apis and to identify a new antifungal agent for this pathogen through minimal inhibitory concentration (MIC) assay and western blot analysis. Macelignan had 1.56 and 3.125 MUg/mL MIC against A. apis after 24 and 48 h, respectively, exhibiting the strongest growth inhibition against A. apis among the tested compounds (corosolic acid, dehydrocostus lactone, loganic acid, tracheloside, fangchinoline and emodin-8-O beta-D-glucopyranoside). Furthermore, macelignan showed a narrow-ranged spectrum against various fungal strains without any mammalian cell cytotoxicity. In spite of miconazole having powerful broad-ranged anti-fungal activity including A. apis, it demonstrated strong cytotoxicity. Therefore, even if macelignan alone was effective as an antifungal agent to treat A. apis, combined treatment with miconazole was more useful to overcome toxicity, drug resistance occurrence and cost effectiveness. Finally, HOG1 was revealed as a target molecule of macelignan in the anti-A. apis activity by inhibiting phosphorylation using S. cerevisiae as a model system. Based on our results, macelignan, a food-grade antimicrobial compound, would be an effective antifungal agent against A. apis infection in bees. PMID- 27383124 TI - Quercetin alleviates pulmonary angiogenesis in a rat model of hepatopulmonary syndrome. AB - Quercetin shows protective effects against hepatopulmonary syndrome (HPS), as demonstrated in a rat model. However, whether these effects involve pulmonary vascular angiogenesis in HPS remains unclear. Therefore, this study aimed to assess the effect of quercetin on pulmonary vascular angiogenesis and explore the underlying mechanisms. Male Sprague-Dawley rats weighing 200-250 g underwent sham operation or common bile duct ligation (CBDL). Two weeks after surgery, HIF 1alpha and NFkappaB levels were assessed in rat lung tissue by immunohistochemistry and western blot. Then, CBDL and sham-operated rats were further divided into 2 subgroups each to receive intraperitoneal administration of quercetin (50 mg/kg daily) or 0.2% Tween for two weeks: Sham (Sham+Tween; n=8), CBDL (CBDL+Tween; n=8), Q (Sham+quercetin; n=8), and CBDL+Q (CBDL+quercetin; n=8). After treatment, lung tissue specimens were assessed for protein (immunohistochemistry and western blot) and/or gene expression (quantitative real-time PCR) levels of relevant disease markers, including VEGFA, VEGFR2, Akt/p-Akt, HIF-1alpha, vWf, and IkappaB/p-IkappaB. Finally, arterial blood was analyzed for alveolar arterial oxygen pressure gradient (AaPO2). Two weeks after CBDL, HIF-1alpha expression in the lung decreased, but was gradually restored at four weeks. Treatment with quercetin did not significantly alter HIF 1alpha levels, but did reduce AaPO2 as well as lung tissue NF-kappaB activity, VEGFA gene and protein levels, Akt activity, and angiogenesis. Although hypoxia is an important feature in HPS, our findings suggest that HIF-1alpha was not the main cause for the VEGFA increase. Interestingly, quercetin inhibited pulmonary vascular angiogenesis in rats with HPS, with involvement of Akt/NF-kappaB and VEGFA/VEGFR-2 pathways. PMID- 27383125 TI - Is Etanar a new biologic? PMID- 27383127 TI - Oxygen-iron interaction in liquid lead-bismuth eutectic alloy. AB - Iron released by steel corrosion was found to be a key impurity in reactions with dissolved oxygen in liquid lead-bismuth eutectic alloys. The iron-oxygen magnetite equilibrium was characterized, allowing the quantification of phenomena that are important for long-term operation of lead-alloy based installations such as corrosion rate control and management of precipitates. PMID- 27383126 TI - Fabrication of water-soluble polymer-encapsulated As4S4 to increase oral bioavailability and chemotherapeutic efficacy in AML mice. AB - Realgar (As4S4) has been demonstrated to be effective for the treatment of acute myeloid leukemia (AML); it has the advantages of no drug resistance and oral administration. Nevertheless, its poor solubility has been an obstacle to its bioavailability, requiring high-dose administration over a long period. We investigated whether crushing realgar crystals to the nanoscale and encapsulating the particles in a water-soluble polymer in one step using hot-melt extrusion would increase the bioavailability of As4S4. Raw As4S4 (r-As4S4) and water soluble polymer were processed via co-rotating twin screw extrusion. The resulting product (e-As4S4) was characterized by SEM, XRD, and DLS. The cytotoxicity and therapeutic effects of e-As4S4 were evaluated in vivo and in vitro. The results show that e-As4S4 dissolved rapidly in water, forming a stable colloid solution. The average size of e-As4S4 particles was 680 nm, which was reduced by more than 40-fold compared with that of r-As4S4. The bioavailability of e-As4S4 was up to 12.6-fold higher than that of r-As4S4, and it inhibited the proliferation of HL-60 cells much more effectively than did r-As4S4, inducing apoptosis and significantly reducing the infiltration of HL-60 cells into the bone marrow, spleen, and liver. This in turn prolonged the survival of AML mice. PMID- 27383129 TI - Noise filtering of composite pulses for singlet-triplet qubits. AB - Semiconductor quantum dot spin qubits are promising candidates for quantum computing. In these systems, the dynamically corrected gates offer considerable reduction of gate errors and are therefore of great interest both theoretically and experimentally. They are, however, designed under the static-noise model and may be considered as low-frequency filters. In this work, we perform a comprehensive theoretical study of the response of a type of dynamically corrected gates, namely the supcode for singlet-triplet qubits, to realistic 1/f noises with frequency spectra 1/omega(alpha). Through randomized benchmarking, we have found that supcode offers improvement of the gate fidelity for alpha 1 and the improvement becomes exponentially more pronounced with the increase of the noise exponent in the range 1 alpha <= 3 studied. On the other hand, for small alpha, supcode will not offer any improvement. The deltaJ-supcode, specifically designed for systems where the nuclear noise is absent, is found to offer additional error reduction than the full supcode for charge noises. The computed filter transfer functions of the supcode gates are also presented. PMID- 27383130 TI - Multidisciplinary intervention to improve albuterol inhaler utilization among patients with asthma. AB - OBJECTIVE: The goal of this study was to examine the impact of a multidisciplinary intervention designed to improve appropriate albuterol inhaler utilization among patients with asthma. METHODS: This was a pre-post retrospective analysis. The study intervention included written information sent directly to patients, educated prescribers, and enhanced pharmacist training on appropriate albuterol inhaler utilization. Eligible study patients had a diagnosis of asthma and purchased at least two albuterol inhalers between 07/12/2012 and 06/30/2013 (pre-period) and 7/01/2013 to 06/30/2014 (post-period). The primary outcome was a comparison between study periods of the count of albuterol inhalers purchased per patient per month (PPPM). RESULTS: The median age of included patients was 41 years, 53% were females, and allergic rhinitis was the most common comorbidity. The median albuterol inhalers purchased PPPM decreased from 0.60 (interquartile range [IQR] = 0.39-0.87) to 0.37 (IQR = 0.26 0.53) from the pre- to post-period (p < 0.001). The proportion of patients with at least one systemic corticosteroid purchase decreased (36% vs. 31%) and >1 albuterol inhaler purchased on the same day increased (3.1% vs. 5.7%) from the pre- to post-period (p < 0.001). Numerically, the proportion of participants who experienced an acute asthma exacerbation decreased and asthma controller inhalers purchased PPPM increased but these did not reach statistical significance (both p > 0.05). CONCLUSIONS: A multidisciplinary approach to increasing appropriate albuterol inhaler use was associated with a decrease in albuterol inhalers purchased PPPM while not increasing acute asthma exacerbations. Future study is needed to evaluate patient perspectives on this intervention and assess its economic impact. PMID- 27383132 TI - Open source posturography. AB - CONCLUSION: The proposed validation goal of 0.9 in intra-class correlation coefficient was reached with the results of this study. With the obtained results we consider that the developed software (RombergLab) is a validated balance assessment software. The reliability of this software is dependent of the used force platform technical specifications. OBJECTIVE: Develop and validate a posturography software and share its source code in open source terms. METHODS: Prospective non-randomized validation study: 20 consecutive adults underwent two balance assessment tests, six condition posturography was performed using a clinical approved software and force platform and the same conditions were measured using the new developed open source software using a low cost force platform. Intra-class correlation index of the sway area obtained from the center of pressure variations in both devices for the six conditions was the main variable used for validation. RESULTS: Excellent concordance between RombergLab and clinical approved force platform was obtained (intra-class correlation coefficient =0.94). A Bland and Altman graphic concordance plot was also obtained. The source code used to develop RombergLab was published in open source terms. PMID- 27383131 TI - Parallel encoding of sensory history and behavioral preference during Caenorhabditis elegans olfactory learning. AB - Sensory experience modifies behavior through both associative and non-associative learning. In Caenorhabditis elegans, pairing odor with food deprivation results in aversive olfactory learning, and pairing odor with food results in appetitive learning. Aversive learning requires nuclear translocation of the cGMP-dependent protein kinase EGL-4 in AWC olfactory neurons and an insulin signal from AIA interneurons. Here we show that the activity of neurons including AIA is acutely required during aversive, but not appetitive, learning. The AIA circuit and AGE 1, an insulin-regulated PI3 kinase, signal to AWC to drive nuclear enrichment of EGL-4 during conditioning. Odor exposure shifts the AWC dynamic range to higher odor concentrations regardless of food pairing or the AIA circuit, whereas AWC coupling to motor circuits is oppositely regulated by aversive and appetitive learning. These results suggest that non-associative sensory adaptation in AWC encodes odor history, while associative behavioral preference is encoded by altered AWC synaptic activity. PMID- 27383134 TI - Tris-ureas as transmembrane anion transporters. AB - Nine tris-urea receptors (L(1)-L(9)) have been synthesised and shown to coordinate to a range of anionic guests both by (1)H NMR titration techniques and single crystal X-ray structural analysis. The compounds have been shown to be capable of mediating the exchange of chloride and nitrate and also chloride and bicarbonate across POPC or POPC : cholesterol 7 : 3 vesicle bilayer membranes at low transporter loadings. An interesting dependency of anion transport on the nature of the cation is evidence to suggest that a M(+)/Cl(-) cotransport process may also contribute to the release of chloride from the vesicles. PMID- 27383133 TI - Revisiting the Measurement of Anomie. AB - Sociologists coined the term "anomie" to describe societies that are characterized by disintegration and deregulation. Extending beyond conceptualizations of anomie that conflate the measurements of anomie as 'a state of society' and as a 'state of mind', we disentangle these conceptualizations and develop an analysis and measure of this phenomenon focusing on anomie as a perception of the 'state of society'. We propose that anomie encompasses two dimensions: a perceived breakdown in social fabric (i.e., disintegration as lack of trust and erosion of moral standards) and a perceived breakdown in leadership (i.e., deregulation as lack of legitimacy and effectiveness of leadership). Across six studies we present evidence for the validity of the new measure, the Perception of Anomie Scale (PAS). Studies 1a and 1b provide evidence for the proposed factor structure and internal consistency of PAS. Studies 2a-c provide evidence of convergent and discriminant validity. Finally, assessing PAS in 28 countries, we show that PAS correlates with national indicators of societal functioning and that PAS predicts national identification and well-being (Studies 3a & 3b). The broader implications of the anomie construct for the study of group processes are discussed. PMID- 27383135 TI - An Artificial Neural Network Based Analysis of Factors Controlling Particle Size in a Virgin Coconut Oil-Based Nanoemulsion System Containing Copper Peptide. AB - A predictive model of a virgin coconut oil (VCO) nanoemulsion system for the topical delivery of copper peptide (an anti-aging compound) was developed using an artificial neural network (ANN) to investigate the factors that influence particle size. Four independent variables including the amount of VCO, Tween 80: Pluronic F68 (T80:PF68), xanthan gum and water were the inputs whereas particle size was taken as the response for the trained network. Genetic algorithms (GA) were used to model the data which were divided into training sets, testing sets and validation sets. The model obtained indicated the high quality performance of the neural network and its capability to identify the critical composition factors for the VCO nanoemulsion. The main factor controlling the particle size was found out to be xanthan gum (28.56%) followed by T80:PF68 (26.9%), VCO (22.8%) and water (21.74%). The formulation containing copper peptide was then successfully prepared using optimum conditions and particle sizes of 120.7 nm were obtained. The final formulation exhibited a zeta potential lower than -25 mV and showed good physical stability towards centrifugation test, freeze-thaw cycle test and storage at temperature 25 degrees C and 45 degrees C. PMID- 27383136 TI - HMGB1 Enhances Drug Resistance and Promotes In Vivo Tumor Growth of Lung Cancer Cells. AB - Drug resistance is an obstacle in the chemotherapeutic treatment of lung cancers. In the present study, the effects of high-mobility group box 1 (HMGB1) protein in chemotherapeutic resistance and the relationships between HMGB1 and chemotherapy drug-induced cell apoptosis or necrosis were clarified. We used cisplatin sensitive A549 cells and cisplatin-resistant A549/DDP cells as cell models with IC50 of 11.58 and 46.95 MUM, respectively. A549/DDP had higher level of HMGB1 compared with A549 cells. Interestingly, with the increasing concentration of DDP, HMGB1 was gradually located into cytoplasm in cisplatin-sensitive A549 cells. Moreover, interference with endogenous HMGB1 sensitized the effects of chemotherapeutic drugs, including 5-Fu, DDP, and OXA. Furthermore, results from an in vivo tumorigenesis experiment demonstrated that serum concentration of HMGB1 was much lower in the group inoculated with HMGB1 shRNA-transfected A549 cells than in the N.C. shRNA-transfected A549 inoculated group, as well as the tumor volume, suggesting that serum HMGB1 contributed to tumor growth in a mouse model. In conclusion, higher levels of HMGB1 probably contributed to chemotherapy drug resistance, and higher serum concentration of HMGB1 promoted in vivo tumor growth. The study would provide new clues to overcome drug resistance in chemotherapy of human lung cancers. PMID- 27383137 TI - Improving Coccyx Radiographs in Emergency Departments. PMID- 27383138 TI - A direct and sustainable synthesis of tertiary butyl esters enabled by flow microreactors. AB - Tertiary butyl esters find large applications in synthetic organic chemistry. A straightforward method for the direct introduction of the tert-butoxycarbonyl group into a variety of organic compounds has been developed using flow microreactor systems. The resultant flow process was more efficient, versatile and sustainable compared to the batch. PMID- 27383139 TI - Management of radioactive waste gases from PET radiopharmaceutical synthesis using cost effective capture systems integrated with a cyclotron safety system. AB - The emphasis on the reduction of gaseous radioactive effluent associated with PET radiochemistry laboratories has increased. Various radioactive gas capture strategies have been employed historically including expensive automated compression systems. We have implemented a new cost-effective strategy employing gas capture bags with electronic feedback that are integrated with the cyclotron safety system. Our strategy is suitable for multiple automated 18F radiosynthesis modules and individual automated 11C radiosynthesis modules. We describe novel gas capture systems that minimize the risk of human error and are routinely used in our facility. PMID- 27383140 TI - Pyrimidine-based fluorescent COX-2 inhibitors: synthesis and biological evaluation. AB - The cyclooxygenase-2 (COX-2) enzyme is overexpressed in a variety of cancers and mediates inflammatory processes that aid the growth and progression of malignancies. Three novel and selective fluorescent COX-2 inhibitors have been designed and synthesized on the basis of previously reported pyrimidine-based COX 2 inhibitors and the 7-nitrobenzofurazan fluorophore. In vitro evaluation of COX 1/COX-2 isozyme inhibition identified N-(2-((7-nitro-benzo[c][1,2,5]oxadiazol-4 yl)amino)propyl)-4-[4-(methylsulfonyl)phenyl]-6-(trifluoro-methyl)-pyrimidin-2 amine (6) as a novel potent and selective COX-2 inhibitor (IC50 = 1.8 MUM). Lead compound (6) was further evaluated for its ability to selectively visualize COX-2 isozyme in COX-2 expressing human colon cancer cell line HCA-7 using confocal microscopy experiments. PMID- 27383141 TI - Production of anti-amoxicillin ScFv antibody and simulation studying its molecular recognition mechanism for penicillins. AB - The molecular recognition mechanism of an antibody for its hapten is very interesting. The objective of this research was to study the intermolecular interactions of an anti-amoxicillin antibody with penicillin drugs. The single chain variable fragment (ScFv) antibody was generated from a hybridoma cell strain excreting the monoclonal antibody for amoxicillin. The recombinant ScFv antibody showed similar recognition ability for penicillins to its parental monoclonal antibody: simultaneous recognizing 11 penicillins with cross reactivities of 18-107%. The three-dimensional structure of the ScFv antibody was simulated by using homology modeling, and its intermolecular interactions with 11 penicillins were studied by using molecular docking. Results showed that three CDRs are involved in antibody recognition; CDR L3 Arg 100, CDR H3 Tyr226, and CDR H3 Arg 228 were the key contact amino acid residues; hydrogen bonding was the main antibody-drug intermolecular force; and the core structure of penicillin drugs was the main antibody binding position. These results could explain the recognition mechanism of anti-amoxicillin antibody for amoxicillin and its analogs. This is the first study reporting the production of ScFv antibody for penicillins and stimulation studying its recognition mechanism. PMID- 27383142 TI - Embedded validity indicators in Conners' CPT-II: Do adult cutoffs work the same way in children? AB - In previous research, several subscales of Conners' CPT-II were found to be useful as performance validity tests (PVTs) when administered to adults with traumatic brain injury (TBI). Furthermore, invalid response sets were associated with inflated scores on several CPT-II scales. The present study proposed to investigate whether these findings would replicate in a pediatric sample. The analyses were based on archival data from 15 children with TBI. The Omissions, Hit RT, Perseverations, and Hit RT BC scales proved effective at differentiating valid and invalid response sets. However, Commission errors were unrelated to scores on PVTs. A composite measure based on these four scores was a superior and more stable validity indicator than individual scales. Two or more T-scores >65 on any of these scales resulted in acceptable overall specificity (.86-1.00) and variable sensitivity (.00-1.00). Scores on CPT-II scales were generally higher among those who failed the reference PVTs. Results suggest that embedded CPT-II validity indices developed in adult TBI samples function similarly in children with TBI, with some notable exceptions. Although the use of adult PVT cutoffs in pediatric assessment is a common practice, and broadly supported by the present findings, there remains a clear need for the independent empirical validation of adult PVTs in children. PMID- 27383143 TI - Outcomes of Pediatric Cataract Surgery in the Copperbelt Province of Zambia. AB - PURPOSE: To study the outcomes of pediatric cataract surgeries in children operated on in the Copperbelt Province of Zambia and the barriers to accessing surgery. METHODS: All children who had congenital, developmental, and traumatic cataracts operated on by lens aspiration, primary posterior capsulotomy, and anterior vitrectomy with posterior chamber intraocular lens implantation from 2012 to 2013 and followed up beyond 6 months were studied. Each child underwent a comprehensive preoperative evaluation. An active, assisted follow-up was done and parents were asked about reasons for delay between presentation and surgery. RESULTS: One hundred two eyes of 70 children met the inclusion criteria of the study. Preoperatively, 76 of 77 (98.7%) eyes in the congenital and developmental cataract group had presenting visual acuity of worse than 6/60. This improved postoperatively, with 19 (29.7%) eyes having best corrected visual acuity (BCVA) of better than 6/18, 23 (35.9%) having BCVA of 6/24 to 6/60, and 22 (34.4%) having BCVA of worse than 6/60. Older age (P = .005), better preoperative vision (P = .045) at presentation, unilaterality (P = .012), and delay between presentation and surgery (P = .004) were predictors of a better postoperative outcome. On multivariate analysis, only age was significant (P = .025). Distance and cost of travel and surgery were the causes of delay in presentation. In the patients with traumatic cataracts, 17 of 25 (68%) had BCVA of better than 6/18, 6 (24%) had BCVA between 6/24 and 6/60, and 2 (8%) had BCVA of worse than 6/60 at the 6-month follow-up. The most common causes of injury were being struck by sticks and stones (10 children, 25%). CONCLUSIONS: Visual outcomes after pediatric cataract surgery in Zambia were comparable and satisfactory. Cost of treatment was a barrier, but delay did not adversely affect outcome. [J Pediatr Ophthalmol Strabismus. 2016;53(5):311-317.]. PMID- 27383144 TI - Success Rates of Conventional Versus Endoscope-Assisted Probing for Congenital Nasolacrimal Duct Obstruction in Children 12 Years and Younger. AB - PURPOSE: To compare the success rates for congenital nasolacrimal duct obstruction (CNLDO) treated with conventional probing versus endoscope-assisted probing. METHODS: A retrospective nonrandomized comparison of the success rates in children (0 to 12 years) with CNLDO who underwent conventional probing or endoscope-assisted probing. Success was defined as absence of tearing or negative fluorescein dye disappearance test. Stent was evaluated. RESULTS: A total of 270 patients with CNLDO comprised the study population. The mean age was 37 months in the conventional probing group and 48.5 months in the endoscope-assisted probing group. The subjective and objective success rates were 76.1% and 75.9%, respectively, in the conventional probing group and 95.7% and 95.7%, respectively, in the endoscope-assisted probing group. The success rates were higher for both methods in the endoscope-assisted probing group (P < .005). The success rate decreased in older children in the conventional probing group (100% < 6 months; 62.5% > 48 months) and remained stable in the endoscope-assisted probing group (100% < 6 months; 97% > 48 months). Stent did not improve success. CONCLUSIONS: Endoscope-assisted probing increased success in older children and children with bilateral obstruction. [J Pediatr Ophthalmol Strabismus. 2016;53(5):292-299.]. PMID- 27383145 TI - Extending accessible chemical space for the identification of novel leads. PMID- 27383147 TI - Role of Myoendothelial Gap Junctions in the Regulation of Human Coronary Artery Smooth Muscle Cell Differentiation by Laminar Shear Stress. AB - BACKGROUND/AIMS: Smooth muscle cells may dedifferentiate into the synthetic phenotype and promote atherosclerosis. Here, we explored the role of myoendothelial gap junctions in phenotypic switching of human coronary artery smooth muscle cells (HCASMCs) co-cultured with human coronary artery endothelial cells (HCAECs) exposed to shear stress. METHODS: HCASMCs and HCAECs were seeded on opposite sides of Transwell inserts, and HCAECs were exposed to laminar shear stress of 12 dyn/cm2 or 5 dyn/cm2. The myoendothelial gap junctions were evaluated by using a multi-photon microscope. RESULTS: In co-culture with HCAECs, HCASMCs exhibited a contractile phenotype, and maintained the expression of differentiation markers MHC and H1-calponin. HCASMCs and HCAECs formed functional intercellular junctions, as evidenced by colocalization of connexin(Cx)40 and Cx43 on cellular projections inside the Transwell membrane and biocytin transfer from HCAECs to HCASMCs. Cx40 siRNA and 18-alpha-GA attenuated protein expression of MHC and H1-calponin in HCASMCs. Shear stress of 5 dyn/cm2 increased Cx43 and decreased Cx40 expression in HCAECs, and partly inhibited biocytin transfer from HCAECs to HCASMCs, which could be completely blocked by Cx43 siRNA or restored by Cx40 DNA transfected into HCAECs. The exposure of HCAECs to shear stress of 5 dyn/cm2 promoted HCASMC phenotypic switching, manifested by morphological changes, decrease in MHC and H1-calponin expression, and increase in platelet derived growth factor (PDGF)-BB release, which was partly rescued by Cx43 siRNA or Cx40 DNA or PDGF receptor signaling inhibitor. CONCLUSIONS: The exposure of HCAECs to shear stress of 5 dyn/cm2 caused the dysfunction of Cx40/Cx43 heterotypic myoendothelial gap junctions, which may be replaced by homotypic Cx43/Cx43 channels, and induced HCASMC transition to the synthetic phenotype associated with the activation of PDGF receptor signaling, which may contribute to shear stress-associated arteriosclerosis. PMID- 27383146 TI - Semi-Automatic Segmentation of Optic Radiations and LGN, and Their Relationship to EEG Alpha Waves. AB - At rest, healthy human brain activity is characterized by large electroencephalography (EEG) fluctuations in the 8-13 Hz range, commonly referred to as the alpha band. Although it is well known that EEG alpha activity varies across individuals, few studies have investigated how this may be related to underlying morphological variations in brain structure. Specifically, it is generally believed that the lateral geniculate nucleus (LGN) and its efferent fibres (optic radiation, OR) play a key role in alpha activity, yet it is unclear whether their shape or size variations contribute to its inter-subject variability. Given the widespread use of EEG alpha in basic and clinical research, addressing this is important, though difficult given the problems associated with reliably segmenting the LGN and OR. For this, we employed a multi modal approach and combined diffusion magnetic resonance imaging (dMRI), functional magnetic resonance imaging (fMRI) and EEG in 20 healthy subjects to measure structure and function, respectively. For the former, we developed a new, semi-automated approach for segmenting the OR and LGN, from which we extracted several structural metrics such as volume, position and diffusivity. Although these measures corresponded well with known morphology based on previous post mortem studies, we nonetheless found that their inter-subject variability was not significantly correlated to alpha power or peak frequency (p >0.05). Our results therefore suggest that alpha variability may be mediated by an alternative structural source and our proposed methodology may in general help in better understanding the influence of anatomy on function such as measured by EEG or fMRI. PMID- 27383148 TI - Fabrication of InGaN thin-film transistors using pulsed sputtering deposition. AB - We report the first demonstration of operational InGaN-based thin-film transistors (TFTs) on glass substrates. The key to our success was coating the glass substrate with a thin amorphous layer of HfO2, which enabled a highly c axis-oriented growth of InGaN films using pulsed sputtering deposition. The electrical characteristics of the thin films were controlled easily by varying their In content. The optimized InGaN-TFTs exhibited a high on/off ratio of ~10(8), a field-effect mobility of ~22 cm(2) V(-1) s(-1), and a maximum current density of ~30 mA/mm. These results lay the foundation for developing high performance electronic devices on glass substrates using group III nitride semiconductors. PMID- 27383149 TI - A novel Plasmodium falciparum rhoptry associated adhesin mediates erythrocyte invasion through the sialic-acid dependent pathway. AB - Erythrocyte invasion by Plasmodium falciparum merozoites is central to blood stage infection and malaria pathogenesis. This intricate process is coordinated by multiple parasite adhesins that bind erythrocyte receptors and mediate invasion through several alternate pathways. P. falciparum expresses 2700 genes during the blood-stages, of which the identity and function of many remains unknown. Here, we have identified and characterized a novel P. falciparum rhoptry associated adhesin (PfRA) that mediates erythrocyte invasion through the sialic acid dependent pathway. PfRA appears to play a significant functional role as it is conserved across different Plasmodium species. It is localized in the rhoptries and further translocated to the merozoite surface. Both native and recombinant PfRA specifically bound erythrocytes in a sialic-acid dependent, chymotrypsin and trypsin resistant manner, which was abrogated by PfRA antibodies confirming a role in erythrocyte invasion. PfRA antibodies inhibited erythrocyte invasion and in combination with antibodies against other parasite ligands produced an additive inhibitory effect, thus validating its important role in erythrocyte invasion. We have thus identified a novel P. falciparum adhesin that binds with a sialic acid containing erythrocyte receptor. Our observations substantiate the strategy to block P. falciparum erythrocyte invasion by simultaneously targeting multiple conserved merozoite antigens involved in alternate invasion pathways. PMID- 27383151 TI - Abstracts from the ASENT 18th Annual Meeting. PMID- 27383150 TI - Update and New Directions in Therapeutics for Neurological Complications of HIV Infections. AB - The pace of therapeutic developments in HIV presents unique challenges to the neurologist caring for patients. Combination antiretroviral therapy (cART) is remarkably effective in suppressing viral replication, preventing, and often even reversing disease progression. Still, not every patient benefits from cART for a variety of reasons, ranging from the cost of therapy and the burden of lifelong daily treatment to side effects and inadequate access to medical care. Treatment failure inevitably leads to disease progression and opportunistic complications. Many of these complications, even those that are treatable, produce permanent neurological disability. With ART, immune recovery itself may paradoxically lead to severe neurological disease; strategies for managing so-called immune reconstitution inflammatory syndrome are beginning to show benefits. Effective cART may nevertheless leave in its wake persistent neurocognitive impairment. Treatments for persistent impairment despite virologic suppression and good immune recovery are being tested but are not yet proven. As we shall see, these treatments target several proposed mechanisms including cerebral small vessel disease, which is highly prevalent in HIV. Most recently, an ambitious initiative has been undertaken to develop interventions to eradicate HIV. This will require elimination of all infectious forms of viral nucleic acid throughout the body. The influence of these interventions on the brain remains to be characterized. Meanwhile, clinical investigators continue to develop antiretroviral treatments that optimize effectiveness, convenience, and tolerability, while minimizing long term toxicities. PMID- 27383153 TI - Editorial - Reworking Drake. PMID- 27383152 TI - Interference effects between memory systems in the acquisition of a skill. AB - There is now converging evidence that the declarative memory system (hippocampus dependent) contributes to sequential motor learning in concert with the procedural memory system (striatum dependent). Because of the competition for shared neuronal resources, introducing a declarative memory task can impair learning of a new motor sequence and interference may occur during the procedural consolidation process. Here, we investigated the extent to which interference effects between memory systems are seen at the retrieval phase of skill learning. Healthy participants were assigned to a control (n = 15) or a declarative condition (n = 15) and trained on a sequence of finger movements (FOS task). Both groups showed similar improvement at the end of the practice session on the first day. Twenty-four hours later, controls were tested solely on the FOS task, while subjects in the declarative condition first engaged in a visuospatial task. Additional offline gains in performance were observed only in the control condition. The introduction of a visuospatial memory task just before retrieval of the motor skill was sufficient to eliminate these gains. This suggests that interference between procedural and declarative memory systems may also occur during subsequent motor recall. It is proposed that the interference effects are linked, in part, to the spatial nature of the motor and declarative tasks, which specifically depends upon hippocampal involvement. PMID- 27383154 TI - Changes in Behavior and Blood Corticosterone Level in Male and Female Rats after Single Administration of Obestatin Fragment 1-4. AB - Single administration of the obestatin fragment 1-4 (300 nmol/kg) to male Wistar rats produced a significant weight loss in male rats on observation days 5-8, while in female rats only on day 8. In addition, males demonstrated decreased risk factor in the elevated plus-maze test, but no effect of the preparation on behavior of female rats was revealed. Obestatin fragment 1-4 had no effect on corticosterone level 1 week after single administration in both females and male rats. PMID- 27383155 TI - Plant Polysaccharides Attenuate Fluorouracil Toxicity for the Small Intestinal Epithelium. AB - Polysaccharides from Tussilago farfara L., Acorus calamus L., and Echinacea purpurea (L.) Moench attenuated the toxic effect of fl uorouracil on the small intestinal epithelium of mice with Lewis lung carcinoma. Addition of polysaccharides to chemotherapy protocols stimulated reparative regeneration processes in the small intestine damaged by the cytostatic treatment. No stimulating effects of the polysaccharides on tumor growth and metastasizing were revealed. PMID- 27383156 TI - Comparative Evaluation of beta-Catenin and E-Cadherin Expression in Liquid Aspiration Biopsy Specimens of Thyroid Nodules. AB - We compared the results of gene molecular and immunocytochemical studies of beta catenin and E-cadherin in different variants of nodular thyroid disease (nodular colloid goiter, follicular thyroid adenocarcinoma, papillary thyroid cancer) and revealed changes of the function of the E-cadherin/beta-catenin complex leading to switching from adhesion function of beta-catenin in nodular colloid goiter to predominantly transcriptional activity in papillary carcinoma. The results confirm the important role of disturbances in E-cadherin-beta-catenin interactions in the mechanisms of malignant transformation of follicular epithelium. PMID- 27383157 TI - Differences in Monoamine Oxidase Activity in the Brain of Wistar and August Rats with High and Low Locomotor Activity: A Cytochemical Study. AB - Monoamine oxidase activity was quantitatively assessed by cytochemical method in brain structures (layers III and V of the sensorimotor cortex, caudate nucleus, nucleus accumbens, hippocampal CA3 field) of rats of August line and Wistar population with high and low locomotor activity in the open fi eld test. Monoamine oxidase activity (substrate tryptamine) predominated in the nucleus accumbens of Wistar rats with high motor activity in comparison with rats with low locomotor activity. In August rats, enzyme activity (substrates tryptamine and serotonin) predominated in the hippocampus of animals with high motor activity. Comparison of August rats with low locomotor activity and Wistar rats with high motor activity (i.e. animals demonstrating maximum differences in motor function) revealed significantly higher activity of the enzyme (substrates tryptamine and serotonin) in the hippocampus of Wistar rats. The study demonstrates clear-cut morphochemical specificity of monoaminergic metabolism based on the differences in the cytochemical parameter "monoamine oxidase activity", in the studied brain structures, responsible for the formation and realization of goal-directed behavior in Wistar and August rats. PMID- 27383159 TI - Repolarization of Heart Ventricles in Dogs during Recovery after Antiorthostatic Hypokinesia. AB - Repolarization properties of ventricular myocardium were studied in anesthetized adult dogs of both sexes subjected to antiorthostatic hypokinesia (head-down tilt at 45 degrees and 60 degrees to the horizontal) and during recovery period (horizontal position for 15 min). The time of repolarization of ventricular myocardium during recovery surpassed the initial value, which represents an adaptive response of the heart to antiorthostasis. PMID- 27383158 TI - Effect of NO Synthase Blockade on Myocardial Contractility of Hypokinetic Rats during Stimulation of beta-Adrenoreceptors. AB - Stimulation of beta-adrenoreceptors with low (10(-8) and 10(-7) M) or high (10( 6) M) doses of isoproterenol in hypokinetic rats treated with L-NAME (a non selective blocker of NO synthases) decreased or increased myocardial contractility, respectively. In control rats, all examined doses of isoproterenol used under blockade of NO synthases inhibited myocardial contractility. PMID- 27383160 TI - Effect of Antidepressants on Immunological Reactivity in ASC Mice with Genetically Determined Depression-Like State. AB - The effect of chronic treatment with antidepressant drugs fluoxetine (20 mg/kg) and imipramine (25 mg/kg) on the number of antibody-producing cells and the main T cell subpopulations in ASC mice characterized by genetic predisposition to depression-like states was studied at the peak of the SE-induced immune response (5*10(8)). Fluoxetine produced an immunostimulatory effect manifested in an increase in the relative and absolute number of IgM antibody-producing cells in the spleen and index of immunoreactivity (CD4/CD8). Administration of fl uoxetine to parental mouse strains without depression (CBA and AKR) had no effect (CBA) or reduced the immune response. The CD4/CD8 ratio did not increase under these conditions. Imipramine was ineffective in the correction of immune reactions in a depression-like state. PMID- 27383161 TI - Relationship between the Size of Magnetic Nanoparticles and Efficiency of MRT Imaging of Cerebral Glioma in Rats. AB - BSA-coated Fe3O4 nanoparticles with different hydrodynamic diameters (36+/-4 and 85+/-10 nm) were synthesized, zeta potential and T2 relaxivity were determined, and their morphology was studied by transmission electron microscopy. Studies on rats with experimental glioma C6 showed that smaller nanoparticles more effectively accumulated in the tumor and circulated longer in brain vessels. Optimization of the hydrodynamic diameter improves the efficiency of MRT contrast agent. PMID- 27383162 TI - Effects of N-[Imino(1-Piperidinyl)Methyl] Guanidine on the Intensity of Free Radical Processes, Aconitase Activity, and Citrate Level in the Tissues of Rats with Experimental Type 2 Diabetes Mellitus. AB - Effects of a synthetic biguanide derivative N-[imino(1-piperidinyl)methyl] guanidine (NIPMG) on free radical homeostasis, aconitase activity, and citrate concentration were studied in the liver and blood serum of rats with type 2 diabetes mellitus. Analysis of biochemiluminescence parameters showed that administration of this agent (10 mg/kg body weight) to animals with diabetes reduced the intensity of free radical processes in study tissues relative to the increased values in untreated diabetic animals. Under these conditions, aconitase activity, a principal target of ROS effects, and citrate level in the liver and blood serum of rats approached the control levels. The results show that NIPMG can positively regulate free radical homeostasis and reduce the intensity of oxidative stress in type 2 diabetes mellitus, which was accompanied by normalization of the studied parameters. PMID- 27383163 TI - IFN-alpha, IFN-beta, and IFN-gamma Have Different Effect on the Production of Proinflammatory Factors Deposited in Weibel-Palade Bodies of Endothelial Cells Infected with Herpes Simplex Virus Type 1. AB - We demonstrated similarities and differences in the effects of IFN-alpha and IFN beta compared to IFN-gamma on the production of factors deposited in the Weibel Palade bodies in cultures of endothelial cells (intact and infected with herpes simplex virus 1). IFN-alpha and IFN-beta reduced the content of von Willebrand factor, endothelin-1, and soluble P-selectin and increased IL-8 concentration in the culture medium of human umbilical vein endothelial cells. IFN-gamma reduced the content of all studied factors in the endothelial cell culture medium. Possible mechanisms of these effects are discussed. PMID- 27383164 TI - New Carbocyclic Amino Acid Derivatives Inhibit Infection Caused by Highly Pathogenic Influenza A Virus Strain (H5N1). AB - New amino acid derivatives with carbocycles of adamantine and quinaldic acid were synthesized and their in vitro antiviral activity against influenza A/H5N1 virus was evaluated. Experiments on cultured embryonic porcine kidney epithelial cells showed that amino acid derivatives suppressed viral replication. Tret butyloxycarbonyl-DL-methionylsulfonyl-1-adamantayl ethylamine and benzyloxycarbonyl-L-trypthophanyl-1-adamantayl ethylamine compounds demonstrated high activity in all in vitro experiments. Moreover, some compounds showed virucidal activity against influenza A/H5N1 virus. PMID- 27383165 TI - Expression of Bax Protein and Morphological Changes in the Myocardium in Experimental Acute Pressure Overload of the Left Ventricle. AB - The expression of Bax protein, marker of intracellular pathway of apoptosis initiation, in viable left ventricular cardiomyocytes and morphological changes in the myocardium in acute pressure overload of the left ventricle were studied in experiment on male rabbits. The content of Bax protein in the cardiomyocyte cytoplasm decreased, this indicating that the mitochondrial pathway was not involved in the realization of the apoptotic program. This decrease was associated with manifest destructive changes in the left ventricular myocardium. PMID- 27383166 TI - Morphofunctional Changes in the Tibial and Peroneal Nerves in Shin Lengthening Using High Speed Daily Distraction Technique. AB - A sustained decrease in the M-response amplitudes of m. gastrocnemius and m. tibialis anterior was revealed during experimental orthopedic shin lengthening in dogs using Ilizarov external fixator with an automated drive (distraction 3 mm/day in 120 steps). Transverse contraction of intrafascicular content (by 13.2%), endoneural hypervascularization (by 28-95%), axonal degeneration and myelin decompactization, and destructive changes of no more than 5% fibers were detected in the tibial nerve. In the peroneal nerve, the contraction reached 17.3%. Endoneurium hypovascularization (by 12%), axonal degeneration and demyelinization, and destructive changes of more than 20% fibers were detected in 6 of 9 experiments. PMID- 27383167 TI - Lentiviral Transduction of Neurons in Adult Brain: Evaluation of Inflammatory Response and Cognitive Effects in Mice. AB - We evaluated the effect of hippocampal injection of lentiviral particles p156-CMV EGFP on behavior, learning, and microglial Iba1(+) cells activation in mice. Testing in the open field and elevated plus-maze revealed higher anxiety levels in lentiviral-injected mice in comparison with animals injected with vehicle. At the same time, lentivirus injection did not change learning and memory of mice in the hippocampal-dependent fear conditioning task. Microglia density in lentivirus injected mice was significantly higher than in vehicle-injected mice. Thus, hippocampal injection of lentiviral particles with minimum content of transgenes produced evident inflammation process, changed anxiety level of experimental animals, but had no effect on hippocampal-dependent learning and memory. PMID- 27383168 TI - Effects of Vascular Peptide Bioregulator on the Density of Microvascular Network in the Brain Cortex of Aged Rats. AB - Using a TV unit for microcirculation studies, we studied the density of the entire microvascular network and its arterial compartment in the pia mater of the sensorimotor cortex in intact young and aged rats (2-3 and 22-24 months) and aged rats after a course of vascular peptide bioregulator Slavinorm. The experiments showed that the density of microvascular network in intact animals decreased by 1.6 times with aging. Treatment with the peptide bioregulator 2.5-fold increased the density of the microvascular network in aged rats in comparison with intact animals of the same age, the density of the arterial compartment of the microvascular network in the pia mater increased by 2.8 times. PMID- 27383169 TI - Preclinical Toxicological Study of Release-Active Preparations for Prediction of Their Pharmacological Activity and Side Effects. AB - We studied chronic toxicity of a few release-active preparations: Dietressa (release-active preparation of affinity-purified antibodies to type 1 cannabinoid receptor), Divasa (releaseactive preparation containing a combination of affinity purified antibodies to brain-specific S-100 protein and endothelial NO-synthase), Cardostin (release-active preparation containing a combination of affinity purified antibodies to C-terminal fragment of angiotensin II type 1 receptor and endothelial NO-synthase), and Bation (release-active preparation containing a combination of affinity-purified antibodies to IFN-gamma and CD4). We evaluated not only side and toxic effects, but also the relationships between these effects and pharmacological activities of the preparations. The data of preclinical toxicological studies of the release-active preparations can be used for prediction of their pharmacological activity. PMID- 27383170 TI - Effects of Intraperitoneal Administration of Mifepristone on Glucocorticoid Status of Experimental Animals. AB - We studied the content of corticosterone and its precursors in the adrenal glands, corticosterone in blood serum and daily urine of rats, and activity of first and second isoforms of 11beta-hydroxysteroid dehydrogenase in the liver and kidneys of rats after 15 daily intraperitoneal injections of 0.9% NaCl or glucocorticoid receptor blocker mifepristone in 0.9% NaCl. Daily injections of NaCl reduced the levels of pregnenolone, progesterone, and corticosterone in the adrenal glands, increased corticosterone excretion with urine, enhanced activity of the first isoform of 11beta-hydroxysteroid dehydrogenase in the liver and reduction in activity of the second isoform of this enzyme in the kidneys. These changes are typical manifestations of chronic stress. Mifepristone restored pregnenolone content in the adrenal glands and increase in corticosterone concentration in the blood. Under these conditions, activity of the first isoform of 11beta-hydroxysteroid dehydrogenase in the liver did not change, and a decrease in activity of the second isoform of the enzyme in the kidneys was less pronounced. The results suggest that mifepristone abolished the stress-mediated increase in activity of the first isoform of 11beta-hydroxysteroid dehydrogenase in the liver and reduced local production of glucocorticoid hormones and their metabolic effects in hepatocytes. PMID- 27383171 TI - Neuroprotective Effectiveness of Intravenous Ubiquinone in Rat Model of Irreversible Cerebral Ischemia. AB - The neuroprotective effect of ubiquinone (coenzyme Q10)was demonstrated on the rats model of ischemic stroke provoked by persistent 24-h occlusion of the middle cerebral artery. Coenzyme Q10 (30 mg/kg) was injected intravenously in 60 min after artery occlusion. Ubiquinone crossed the blood-brain barrier, accumulated in the brain, and produced a neuroprotective effect: it alleviated ischemia induced neurological deficit and reduced the size of necrotic zone by 49% in comparison with rats receiving physiological saline. PMID- 27383172 TI - Radioprotective and Apoptotic Properties of a Combination of alpha-Tocopherol Acetate and Ascorbic Acid. AB - We studied radioprotective and apoptotic properties of a combination of alpha tocopherol acetate and ascorbic acid. alpha-Tocopherol acetate (10 mg/kg body weight) or ascorbic acid (20 mg/kg) or combination of these agents in the same doses was orally administered to male rats at various terms before and after single whole-body exposure to gamma-irradiation in the doses of 2 and 8 Gy. Irradiation increased the frequency of chromosome aberrations in bone marrow cells and plasma level of low-molecular-weight DNA. Vitamin combination administered before or after irradiation significantly reduced the frequency of chromosome aberrations by 2-2.5 times. Administration of this combination 10 min before irradiation 1.5-fold increased the content of low-molecular-weight DNA in blood plasma in comparison with the control animals exposed to radiation. The combination of alpha-tocopherol acetate and ascorbic acid produced radioprotective effects and enhanced apoptosis in irradiated cells. PMID- 27383173 TI - Atrial Natriuretic Peptide Inhibits Spontaneous Contractile Activity of Lymph Nodes. AB - Atrial natriuretic peptide dose-dependently inhibited spontaneous phase and tonic activity of smooth muscle strips from the capsule of isolated bovine mesenteric lymph nodes. Pretreatment with L-NAME, diclofenac, and methylene blue had practically no effect on the peptide-induced relaxation responses. In contrast, glibenclamide significantly reduced the inhibitory effect of atrial natriuretic peptide. We suppose that the NO-dependent and cyclooxygenase signaling pathways are not involved in implementation of the inhibitory effects of atrial natriuretic peptide. ATP-sensitive K(+)-channels of the smooth muscle cell membrane are the last component in the signaling pathway leading to relaxation of smooth muscles of the lymph node capsule caused by atrial natriuretic peptide; activation of these channels leads to membrane hyperpolarization and smooth muscle relaxation. PMID- 27383174 TI - Dominant and Non-Dominant Frequency Structure of Evoked Ventricular Fibrillation in Dogs with Myocardial Ischemia. AB - The first 10 min of electrically provoked ventricular fibrillation in dogs with ischemic heart disease were characterized by organized myocardial activity evidenced by the dominant ECG frequency structure. During the first 2 min of ventricular fibrillation, low-frequency oscillations (4-7 Hz) dominated, while on min 3 to 10 after the onset of fibrillation, the dominant frequencies were low and medium (4-12 Hz). After 10-min fibrillation, the oscillations became non dominant. Thus, ischemic myocardium maintains the organized structure of ventricular fibrillation for the first 10 min, which is important for the development of automatic diagnostics of abnormal cardiac activity in humans. PMID- 27383175 TI - Implication of JAK1, JAK2, and JAK3 in the Realization of Proliferation and Differentiation Potential of Mesenchymal Progenitor Cells In Vitro. AB - Involvement of individual JAK kinases in the realization of growth potential of mesenchymal progenitor cells was examined in vitro. Important role of JAK2 and JAK3 in determining the initial level of mitotic activity of progenitor cells was established. The yield of fibroblast CFUF was suppressed under the effect of specific inhibitors of JAK kinases. Blockade of JAK3 increased the rate of progenitor element differentiation. JAK1 had no effect on proliferation and differentiation status of progenitor cells. PMID- 27383176 TI - Cardiac Autonomic Drive during Arterial Hypertension and Metabolic Disturbances. AB - ANS support of the cardiac work was assessed with analysis of heart rate variability in representative samples of patients with arterial hypertension and metabolic disturbances manifested by overweight, classes I-II obesity, compromised glucose tolerance, and type II diabetes. Initially enhanced sympathetic effects on the heart rate demonstrated no further increase during the orthostatic test in contrast to suprasegmentary influences enhanced by this test. The pronouncedness of revealed peculiarities in ANS drive to the heart correlated with metabolic disturbances, and these peculiarities attained maximum in patients with type II diabetes. PMID- 27383177 TI - Effect of Audiogenic Seizures on the Dynamics of Fatty Acid Composition of Hippocampal Dental Gyrus in Krushinsky-Molodkina Rats. AB - Changes in the fatty acid composition of the hippocampal dentate gyrus in Krushinsky-Molodkina rats with hereditary predisposition to audiogenic seizures were studied in 1, 3, and 14 days after 1 or 5 seizures. Seizure activity changed the content of saturated and monounsaturated as well as polyunsaturated fatty acids at different terms after seizures. After seizures, the content of individual fatty acids changed in different directions. Similar shifts after 1 and 5 seizures were observed only for eicosapentaenoic acid at all observation terms. More pronounced changes in fatty acid composition were observed after 5 seizures. These results can be useful for the development of new approaches to correction of seizure activity. PMID- 27383178 TI - [IgG4-associated diseases]. PMID- 27383179 TI - [Capillary microscopy]. PMID- 27383180 TI - [Antiphospholipid syndrome]. PMID- 27383181 TI - The impact of glycemic variability on diabetic peripheral neuropathy. AB - Mean glucose values alone cannot explain the patterns of morbidity and mortality due to dysglycemia in diabetes. Development of continuous glucose monitoring systems has improved the analysis and interpretation of glycemic variability. The roles of glycemic components other than constant hyperglycemia in diabetic complications must be investigated because large clinical studies have indicated that risk factors besides the average glucose value of HbA1c are involved in chronic macrocomplications/microcomplications of diabetes. Among these complications, the pathogenesis of diabetic peripheral neuropathy is particularly complex, and several factors related to glucose and nonglucose pathways have been suggested as risk factors. There is little information regarding the effect of glycemic variability on diabetic peripheral neuropathy, unlike other microvascular complications of retinopathy and nephropathy, and whether glycemic variability causes harmful effects is still a matter of debate. In this review, we discuss the relationships between glycemic variability and diabetic peripheral neuropathy, focusing on somatosensory peripheral neuropathies rather than autonomic neuropathies. PMID- 27383182 TI - Numb and Numbl act to determine mammary myoepithelial cell fate, maintain epithelial identity, and support lactogenesis. AB - Mammary epithelium is comprised of an inner layer of luminal epithelial cells and an outer layer of contractile myoepithelial cells with mesenchymal properties. These two compartments interact throughout mammary morphogenesis to form branching ducts during puberty and terminate in secretory alveoli during lactation. It is not known how the myoepithelial cell lineage is specified, nor how signals in myoepithelial cells contribute to lactogenesis. Here, we show that Numb and Numbl are enriched in mammary myoepithelial cells, with their expression peaking during pregnancy. We use conditional Numb- and Numbl-knockout mouse models to demonstrate that loss of Numb/Numbl compromised the myoepithelial layer and expanded the luminal layer, led epithelial cells to undergo epithelial-to mesenchymal transition, and resulted in lactation failure as a result of abnormal alveolar formation during pregnancy. Numb and Numbl function via repression of the Notch signaling pathway and of the p53-p21 axis during mammary gland development. These findings highlight the importance of Numb and Numbl in the control of myoepithelial cell fate determination, epithelial identity, and lactogenesis.-Zhang Y., Li, F., Song, Y., Sheng, X., Ren, F., Xiong, K., Chen, L., Zhang, H., Liu, D., Lengner, C. J., Xue, L., Yu, Z. Numb and Numbl act to determine mammary myoepithelial cell fate, maintain epithelial identity, and support lactogenesis. PMID- 27383183 TI - Altered TGF-alpha/beta signaling drives cooperation between breast cancer cell populations. AB - The role of tumor heterogeneity in regulating disease progression is poorly understood. We hypothesized that interactions between subpopulations of cancer cells can affect the progression of tumors selecting for a more aggressive phenotype. We developed an in vivo assay based on the immortalized nontumorigenic breast cell line MCF10A and its Ras-transformed derivatives AT1 (mildly tumorigenic) and CA1d (highly tumorigenic). CA1d cells outcompeted MCF10A, forming invasive tumors. AT1 grafts were approximately 1% the size of CA1d tumors when initiated using identical cell numbers. In contrast, CA1d/AT1 mixed tumors were larger than tumors composed of AT1 alone (100-fold) or CA1d (3-fold), suggesting cooperation in tumor growth. One of the mechanisms whereby CA1d and AT1 were found to cooperate was by modulation of TGF-alpha and TGF-beta signaling. Both of these molecules were sufficient to induce changes in AT1 proliferative potential in vitro. Reisolation of AT1 tumor-derived (AT1-TD) cells from these mixed tumors revealed that AT1-TD cells grew in vivo, forming tumors as large as tumorigenic CA1d cells. Cooperation between subpopulations of cancer epithelium is an understudied mechanism of tumor growth and invasion that may have implications on tumor resistance to current therapies.-Franco, O. E., Tyson, D. R., Konvinse, K. C., Udyavar, A. R., Estrada, L., Quaranta, V., Crawford, S. E., Hayward, S. W. Altered TGF-alpha/beta signaling drives cooperation between breast cancer cell populations. PMID- 27383185 TI - Brexit: the decision of a divided country. PMID- 27383184 TI - Understanding Factors That Modulate the Establishment of HIV Latency in Resting CD4+ T-Cells In Vitro. AB - Developing robust in vitro models of HIV latency is needed to better understand how latency is established, maintained and reversed. In this study, we examined the effects of donor variability, HIV titre and co-receptor usage on establishing HIV latency in vitro using two models of HIV latency. Using the CCL19 model of HIV latency, we found that in up to 50% of donors, CCL19 enhanced latent infection of resting CD4+ T-cells by CXCR4-tropic HIV in the presence of low dose IL-2. Increasing the infectious titre of CXCR4-tropic HIV increased both productive and latent infection of resting CD4+ T-cells. In a different model where myeloid dendritic cells (mDC) were co-cultured with resting CD4+ T-cells, we observed a higher frequency of latently infected cells in vitro than CCL19 treated or unstimulated CD4+ T-cells in the presence of low dose IL-2. In the DC T-cell model, latency was established with both CCR5- and CXCR4-tropic virus but higher titres of CCR5-tropic virus was required in most donors. The establishment of latency in vitro through direct infection of resting CD4+ T-cells is significantly enhanced by CCL19 and mDC, but the efficiency is dependent on virus titre, co-receptor usage and there is significant donor variability. PMID- 27383187 TI - Disclosure UK: transparency should no longer be an optional extra. PMID- 27383186 TI - The Effects of a Locally Developed mHealth Intervention on Delivery and Postnatal Care Utilization; A Prospective Controlled Evaluation among Health Centres in Ethiopia. AB - BACKGROUND: Although there are studies showing that mobile phone solutions can improve health service delivery outcomes in the developed world, there is little empirical evidence that demonstrates the impact of mHealth interventions on key maternal health outcomes in low income settings. METHODS: A non-randomized controlled study was conducted in the Amhara region, Ethiopia in 10 health facilities (5 intervention, 5 control) together serving around 250,000 people. Health workers in the intervention group received an android phone (3 phones per facility) loaded with an application that sends reminders for scheduled visits during antenatal care (ANC), delivery and postnatal care (PNC), and educational messages on dangers signs and common complaints during pregnancy. The intervention was developed at Addis Ababa University in Ethiopia. Primary outcomes were the percentage of women who had at least 4 ANC visits, institutional delivery and PNC visits at the health center after 12 months of implementation of the intervention. FINDINGS: Overall 933 and 1037 women were included in the cross-sectional surveys at baseline and at follow-up respectively. In addition, the medical records of 1224 women who had at least one antenatal care visit were followed in the longitudinal study. Women who had their ANC visit in the intervention health centers were significantly more likely to deliver their baby in the same health center compared to the control group (43.1% versus 28.4%; Adjusted Odds Ratio (AOR): 1.98 (95%CI 1.53-2.55)). A significantly higher percentage of women who had ANC in the intervention group had PNC in the same health center compared to the control health centers (41.2% versus 21.1%: AOR: 2.77 (95%CI 2.12-3.61)). CONCLUSIONS: Our findings demonstrated that a locally customized mHealth application during ANC can significantly improve delivery and postnatal care service utilization possibly through positively influencing the behavior of health workers and their clients. PMID- 27383188 TI - Mixed epithelial and stromal tumor of kidney with renal vein extension: an unusual case report and review of literature. AB - Mixed epithelial and stromal tumor of kidney (MESTK) is a rare but distinct renal complex neoplasm composed of a mixture of mesenchymal and epithelial elements with characteristic ovarian-type stroma. Due to its relative rarity, little is known about the histogenesis and prognostic factors of this tumor. Although most reported cases display bland histological features and benign clinical course, a few cases of malignant MESTK have been described. We report an unusual case of MESTK in a 50-year-old female patient with renal venous involvement. Macroscopically, the tumor was solid and unencapsulated in the central region of left kidney. There was a polypoid mass with slender pedicle found to extend into the renal vein forming an intravenous tumor thrombus. Histologically, both renal and intravenous mass were composed of bland spindle-shaped cells and round dilated tubules lined by epithelium without any cytological atypia. The spindle cells were diffusely positive for smooth muscle actin and desmin, while tubules were positive for pan-cytokeratin (AE1/AE3). A diagnosis of MESTK with renal vein extension was made. The patient received no adjuvant treatment after radical nephrectomy. There was no sign of recurrence or metastasis of tumor found in a period of 16-month regular follow-up. To our knowledge, this is the first case of MESTK with renal vein extension, but lacking malignant histological appearance. Additional studies of MESTK with vein involvement will be needed to determine whether this imparts any adverse behavior, similar to other benign renal tumors with vascular involvement. PMID- 27383189 TI - Utilisation of health services and the poor: deconstructing wealth-based differences in facility-based delivery in the Philippines. AB - BACKGROUND: Despite achieving some success, wealth-related disparities in the utilisation of maternal and child health services persist in the Philippines. The aim of this study is to decompose the principal factors driving the wealth-based utilisation gap. METHODS: Using national representative data from the 2013 Philippines Demographic and Health Survey, we examine the extent overall differences in the utilisation of maternal health services can be explained by observable factors. We apply nonlinear Blinder-Oaxaca-type decomposition methods to quantify the effect of differences in measurable characteristics on the wealth based coverage gap in facility-based delivery. RESULTS: The mean coverage of facility-based deliveries was respectively 41.1 % and 74.6 % for poor and non poor households. Between 67 and 69 % of the wealth-based coverage gap was explained by differences in observed characteristics. After controlling for factors characterising the socioeconomic status of the household (i.e. the mothers' and her partners' education and occupation), the birth order of the child was the major factor contributing to the disparity. Mothers' religion and the subjective distance to the health facility were also noteworthy. CONCLUSIONS: This study has found moderate wealth-based disparities in the utilisation of institutional delivery in the Philippines. The results confirm the importance of recent efforts made by the Philippine government to implement equitable, pro-poor focused health programs in the most deprived geographic areas of the country. The importance of addressing the social determinants of health, particularly education, as well as developing and implementing effective strategies to encourage institutional delivery for higher order births, should be prioritised. PMID- 27383190 TI - The usefulness of fluorine-18 fluorodeoxyglucose PET in the detection of recurrence in patients with differentiated thyroid cancer with elevated thyroglobulin and negative radioiodine whole-body scan. AB - INTRODUCTION: PET/computed tomography (CT) using fluorine-18 fluorodeoxyglucose (F-FDG) has been used in the diagnosis of recurrence and metastases of differentiated thyroid cancer (DTC) in cases of negative whole-body scan (WBS) despite elevated concentrations of stimulated thyroglobulin (Tg). AIM: To assess the utility of PET/CT in the detection of recurrence among patients with DTC with increased Tg levels and negative results of WBS. MATERIALS AND METHODS: PET/CT results were retrospectively analyzed in patients with DTC with increased Tg and negative results of WBS as well as negative cervical ultrasonography and chest radiography. PET-CT was performed 1-2 weeks after recent diagnostics under conditions of endogenous or exogenous thyroid-stimulating hormone stimulation. PET/CT was performed using a Discovery ST scanner 1 h after an intravenously F FDG injection (activity 4-5 MBq/kg). To determine the cutoff value of Tg, receiver operating characteristic curves were analyzed. RESULTS: Sixty-nine patients with DTC (48 women, 21 men) aged 22-83 years (mean 50.9+/-17.5 years) were qualified. In 44 patients (63.8%), PET/CT indicated lesions of DTC. Thirty (43.5%) patients had F-FDG positive findings. In the remaining 14 patients (20.3%), lesions were found in CT only. Patients with a positive PET/CT scan had significantly higher Tg values than patients with a negative PET/CT (mean 143.8 vs. 26.5 ng/ml, P=0.03). The cutoff value of Tg concentration measured with the receiver operating characteristic analysis was 32.9 ng/ml. CONCLUSION: PET/CT is a useful tool in the detection of recurrence among thyroid cancer patients in cases of conflicting results of standard procedures, particularly for those with high Tg levels and negative WBS. The probability of obtaining a positive PET-CT result increases with the level of Tg. PMID- 27383191 TI - Comparison between a count-based and geometrical approach for the assessment of left ventricular dyssynchrony using myocardial perfusion scintigraphy. AB - OBJECTIVE: There are two distinct approaches for the assessment of left ventricular (LV) dyssynchrony by myocardial perfusion scintigraphy (MPS). The aim of this study was to compare the performance of the count-based and geometrical approach in clinical data using gated single photon emission computed tomography MPS. MATERIAL AND METHODS: Group 1 consisted of 113 patients (49 men, 64 women) with normal perfusion [summed rest score (SRS)<=3], normal LV ejection fraction (>=55%), and normal QRS duration (QRSd<120 ms). Group 2 consisted of 89 heart failure patients (79 men, 10 women) with no restriction for SRS, LV ejection fraction <=35%, and QRSd >=120 ms. All MPS parameters were obtained from the software Corridor4DM. Dyssynchrony parameters used were time to peak contraction, SD, and bandwidth (BW). RESULTS: SD and BW were estimated higher (difference group 1: SD 3.0+/-2.3 and BW 11.3+/-9.3, P-values <0.001; difference group 2: SD 2.4+/-4.3 and BW 1.3+/-17.0, P-value <0.001 and 0.479 respectively) using the count-based approach in comparison with the geometrical method. A significant and good correlation was found between these two methods (R=0.763, 0.902, 0.896 for time to peak contraction, SD, and BW respectively, P-values <=0.001). SD and BW in both approaches were equally good parameters for differentiating heart failure patients (area under the curve: 0.995-0.998), although using different cut-off values. CONCLUSION: The count-based approach generally provides a wider phase distribution and subsequently greater SD and BW estimates compared with the geometrical algorithm. These differences result in clinically relevant deviations in normal and cut-off values that have to be recognized when evaluating patients. PMID- 27383192 TI - Specificity of Genetic Biomarker Studies in Cancer Research: A Systematic Review. AB - As genetic information becomes more readily available, there is increasing demand from both patients and providers to develop personalized approaches to cancer care. Investigators are increasingly reporting numbers of studies correlating genomic signatures and other biomarkers to survival endpoints. The extent to which cancer-specific and non-specific effects are reported in contemporary studies is unknown. In this review of 85 high-impact studies associating genetic biomarkers with cancer outcomes, 95% reported significant associations with event free survival outcomes, yet less than half reported effects on a cancer-specific endpoint. This methodology leaves open the possibility that observed associations are unrelated to cancer. PMID- 27383194 TI - Cross-linking of lens crystallin proteins induced by tryptophan metabolites and metal ions: implications for cataract development. AB - Long-wavelength solar UV radiation is implicated in photodamage to the human eye. The human lens contains multiple tryptophan-derived compounds that have significant absorbance bands in the UVA region (lambda 315-400 nm) that act as efficient physical filters for these wavelengths. The concentrations of many of these UV filter compounds decrease with increase in age, resulting in diminished protection, increased oxidative damage and the accumulation of modified proteins implicated in nuclear cataract formation. This damage may arise via the formation of alpha,beta-unsaturated carbonyls from the UV filter compounds, adduction to lens proteins and subsequent action as photosensitizers, and/or via the reactions of redox-active transition metal ions that accumulate in aged human lenses. The latter may promote the oxidation of free, or protein-bound, o-aminophenols, such as the UV filter compounds 3-hydroxykynurenine (3OHKyn) and 3-hydroxyanthranilic acid (3OHAA). It is shown here that Cu(II), and to a lesser extent Fe(III), enhance oxidation of free 3OHKyn, 3OHAA and 3OHKyn bound to specific amino acids and lens proteins, with this resulting in increased cross-linking of lens proteins. These data indicate that elevated levels of transition metal ions in aging lenses can enhance the loss of protective UV filter compounds, and contribute to the formation of high-molecular-mass dysfunctional crystallin proteins in a light-independent manner. These reactions may contribute to the formation of lens cataracts in humans. PMID- 27383193 TI - Alterations in Caveolin-1 Expression and Receptor-Operated Ca2+ Entry in the Aortas of Rats with Pulmonary Hypertension. AB - BACKGROUND/AIMS: Alterations in intracellular Ca2+ concentration ([Ca2+]i) underlie the pathogenesis of various cardiovascular diseases. Caveolin-1 (Cav-1) is the primary functional protein associated with caveolae, which are invaginations in the plasma membrane, and is a regulator of [Ca2+]i signaling. Caveolae and Cav-1 increase the activity of store-operated Ca2+ channels (SOCC) in rat pulmonary arterial smooth muscle cells (PASMCs), and these enhancing effects were more pronounced in rats with pulmonary hypertension (PH). Classical transient receptor potential (TRPC) proteins are highly expressed in vascular smooth muscle cells, and these proteins form functional receptor-operated Ca2+ channels (ROCC) and SOCC in PASMCs. Previous studies suggested that functional and structural changes in aortas might occur during the pathological process of PH. Our data demonstrated that Cav-1 and TRPC were also abundant in the aorta smooth muscle cells (AoSMCs) of PH rats. However, previous PH research primarily focused on Ca2+ channels in pulmonary arteries, but not functional changes in Ca2+ channels in aortas. The contribution of Cav-1 of AoSMCs to alterations of Ca2+ signaling in aortic functions during the pathological process of PH has not been fully characterized. Therefore, this study investigated alterations in Cav-1 expression and the relationship of these changes to Ca2+ channels in AoSMCs of PH rats. METHODS: The present study examined physiological caveolae and Cav-1 expression and characterized the function of altered Cav-1 expression in rat aortas with PH. RESULTS: The appearance of caveolae with Cav-1 expression increased significantly in the aortas of rats with PH, but TRPC1 and TRPC6 expression was not altered. In vitro experiments demonstrated that caveolae contributed to phenylephrine, endothelin-1, and 1-oleoyl-2-acetyl-sn-glycerol (OAG)-induced aortic vasoreactivity, but KCl and cyclopiazonic acid had no effect, which suggests the vital ability of Cav-1 to regulate ROCC activity. The introduction of Cav-1 scaffolding domain peptide enhanced OAG-induced ROCC function in primary AoSMCs. CONCLUSION: Cav-1 is specifically associated with ROCC in aortas and plays a vital role in altering vasoreactivity, which affects cardiovascular diseases pathology. Caveolae and Cav-1 up-regulation may affect the function of ROCC in rat models of PH. PMID- 27383195 TI - Quantitative Determination of Flexible Pharmacological Mechanisms Based On Topological Variation in Mice Anti-Ischemic Modular Networks. AB - Targeting modules or signalings may open a new path to understanding the complex pharmacological mechanisms of reversing disease processes. However, determining how to quantify the structural alteration of these signalings or modules in pharmacological networks poses a great challenge towards realizing rational drug use in clinical medicine. Here, we explore a novel approach for dynamic comparative and quantitative analysis of the topological structural variation of modules in molecular networks, proposing the concept of allosteric modules (AMs). Based on the ischemic brain of mice, we optimize module distribution in different compound-dependent modular networks by using the minimum entropy criterion and then calculate the variation in similarity values of AMs under various conditions using a novel method of SimiNEF. The diverse pharmacological dynamic stereo scrolls of AMs with functional gradient alteration, which consist of five types of AMs, may robustly deconstruct modular networks under the same ischemic conditions. The concept of AMs can not only integrate the responsive mechanisms of different compounds based on topological cascading variation but also obtain valuable structural information about disease and pharmacological networks beyond pathway analysis. We thereby provide a new systemic quantitative strategy for rationally determining pharmacological mechanisms of altered modular networks based on topological variation. PMID- 27383197 TI - Safety Assessment of Nitrocellulose and Collodion as Used in Cosmetics. AB - The Cosmetic Ingredient Review Expert Panel (the Panel) assessed the safety of nitrocellulose and collodion as used in cosmetics, concluding that these ingredients are safe in the present practices of use and concentration in cosmetic formulations. Both ingredients are used almost exclusively in nail product formulations. The maximum concentration of use of nitrocellulose in nail polish and enamels is 22%; for collodion, the maximum reported concentration of use in nail polish and enamel is 14%. The Panel reviewed available animal and clinical data in making its determination of safety. PMID- 27383196 TI - Chronic pistachio intake modulates circulating microRNAs related to glucose metabolism and insulin resistance in prediabetic subjects. AB - PURPOSE: To assess the effects of a pistachio-enriched diet on the profile of circulating microRNAs (miRNAs) related to glucose metabolism and insulin resistance (IR). METHODS: Randomized crossover clinical trial in 49 subjects with prediabetes was performed. Subjects consumed a pistachio-supplemented diet (PD, 50 % carbohydrates, 33 % fat, including 57 g/day of pistachios) and an isocaloric control diet (CD, 55 % carbohydrates and 30 % fat) for 4 months each, separated by a 2-week washout period. The plasma profile of a set of seven predefined miRNAs related to glucose and insulin metabolism was analyzed by quantitative RT PCR. RESULTS: After the PD period, subjects have shown significant lower circulating levels of miR-192 and miR-375 compared to CD period, whereas miR-21 nonsignificantly increased after PD compared with CD (47 vs. 2 %, P = 0.092). Interestingly, changes in circulating miR-192 and miR-375 were positively correlated with plasma glucose, insulin and HOMA-IR. CONCLUSION: Chronic pistachio consumption positively modulates the expression of some miRNA previously implicated on insulin sensitivity. PMID- 27383198 TI - Safety Assessment of Microbial Polysaccharide Gums as Used in Cosmetics. AB - The Cosmetic Ingredient Review Expert Panel assessed the safety of 34 microbial polysaccharide gums for use in cosmetics, finding that these ingredients are safe in cosmetic formulations in the present practices of use and concentration. The microbial polysaccharide gums named in this report have a variety of reported functions in cosmetics, including emulsion stabilizer, film former, binder, viscosity-increasing agent, and skin-conditioning agent. The Panel reviewed available animal and clinical data in making its determination of safety. PMID- 27383199 TI - Safety Assessment of Alkyl PEG/PPG Ethers as Used in Cosmetics. AB - The Cosmetic Ingredient Review (CIR) Expert Panel assessed the safety of 131 alkyl polyethylene glycol (PEG)/polypropylene glycol ethers as used in cosmetics, concluding that these ingredients are safe in the present practices of use and concentration described in this safety assessment when formulated to be nonirritating. Most of the alkyl PEG/PPG ethers included in this review are reported to function in cosmetics as surfactants, skin-conditioning agents, and/or emulsifying agents. The alkyl PEG/PPG ethers share very similar physiochemical properties as the alkyl PEG ethers, which were reviewed previously by the CIR Expert Panel and found safe when formulated to be nonirritating. The alkyl PEG ethers differ by the inclusion of PPG repeat units, which are used to fine-tune the surfactant properties of this group. The Panel relied heavily on data on analogous ingredients, extracted from the alkyl PEG ethers and PPG reports, when making its determination of safety. PMID- 27383200 TI - Posterior atlantoaxial fusion as treatment option for extracranial vertebral artery dissecting aneurysm: a case report and literature review. AB - Symptomatic extracranial vertebral artery (VA) dissection may need surgery. We describe such a case successfully treated with atlantoaxial fusion based on its rare dynamic angiographic findings. A 27-year-old woman suffered from repeated brainstem and cerebellar infarctions from a left extracranial VA dissecting aneurysm. Dynamic angiography showed the dissecting aneurysm of the V3 segment in the neutral head position, and deflation of the aneurysm during rightward head rotation. She underwent posterior atlantoaxial fusion, and the lesion was repaired with no subsequent ischemia. Posterior atlantoaxial fusion can be an option for some extracranial VA dissections with preserving its anterograde blood flow. PMID- 27383201 TI - Long-term clinical outcomes of spinal accessory nerve transfer to the suprascapular nerve in patients with brachial plexus palsy. AB - BACKGROUND: For the reconstruction of brachial plexus lesions, restoration of elbow flexion and shoulder function is fundamental and is achieved by dual nerve transfers. Shoulder stabilization and movement are crucial in freedom of motion of the upper extremity. In patients with C5-C6 brachial plexus injury, spinal accessory nerve transfer to the suprascapular nerve and a fascicle of ulnar nerve to musculocutaneous nerve (dual nerve transfer) are carried out for restoration of shoulder abduction and elbow flexion, respectively. In the present study, we evaluated the long-term clinical outcomes of spinal accessory nerve transfer to the suprascapular nerve for restoration of shoulder abduction in patients with brachial plexus palsy undergoing a dual nerve transfer. PATIENTS AND METHODS: In the present retrospective review, 22 consecutive subjects with upper brachial plexus palsy were assessed. All of the subjects underwent spinal accessory nerve transfer to the suprascapular nerve and a dual nerve transfer from the ulnar nerve to the biceps branch and from the median nerve to the brachialis branch of the musculocutaneous nerve simultaneously. All of the subjects were followed up for 18 to 24 months (average, 21.7 months) for assessing the recovery of the shoulder abduction and motor function. RESULTS: Spinal accessory nerve transfer to the suprascapular nerve showed a motor function recovery of M3 and M4 in 13.6 and 63.6% of the subjects, respectively. However, 22.7 % of the subjects remained with a motor function of M2. The mean of shoulder abduction reached 55.55 +/- 9.95 degrees (range, 40-72 degrees ). Altogether, good functional results regained in 17 out of 22 the subjects (77.2 %). Linear regression analysis showed that advanced age was a predictor of low motor functional grade. CONCLUSIONS: The evidence from the present study suggests that transferring spinal accessory nerve to the suprascapular nerve for restoring shoulder abduction is an effective and reliable treatment with high success rate in patients with brachial plexus palsy, especially in young patients. PMID- 27383202 TI - Thrombotic Thrombocytopenic Purpura in Black People: Impact of Ethnicity on Survival and Genetic Risk Factors. AB - Black people are at increased risk of thrombotic thrombocytopenic purpura (TTP). Whether clinical presentation of TTP in Black patients has specific features is unknown. We assessed here differences in TTP presentation and outcome between Black and White patients. Clinical presentation was comparable between both ethnic groups. However, prognosis differed with a lower death rate in Black patients than in White patients (2.7% versus 11.6%, respectively, P = .04). Ethnicity, increasing age and neurologic involvement were retained as risk factors for death in a multivariable model (P < .05 all). Sixty-day overall survival estimated by the Kaplan-Meier curves and compared with the Log-Rank test confirmed that Black patients had a better survival than White patients (P = .03). Salvage therapies were similarly performed between both groups, suggesting that disease severity was comparable. The comparison of HLA-DRB1*11, -DRB1*04 and -DQB1*03 allele frequencies between Black patients and healthy Black individuals revealed no significant difference. However, the protective allele against TTP, HLA-DRB1*04, was dramatically decreased in Black individuals in comparison with White individuals. Black people with TTP may have a better survival than White patients despite a comparable disease severity. A low natural frequency of HLA DRB1*04 in Black ethnicity may account for the greater risk of TTP in this population. PMID- 27383203 TI - Smad2/3/4 Pathway Contributes to TGF-beta-Induced MiRNA-181b Expression to Promote Gastric Cancer Metastasis by Targeting Timp3. AB - BACKGROUND/AIMS: Transforming growth factor beta (TGF-beta) plays a major role in tumorigenesis. MicroRNA-181b (miRNA-181b) is a multifaceted miRNA that has been implicated in many cellular processes such as cell fate determination and cellular invasion. This study aimed to confirm the relationship of miRNA-181b and the TGF-beta-Smad2/3/4 pathway with the induction of the epithelial-to mesenchymal transition (EMT) in gastric cancer. METHODS: This study investigated the ability of TGF-beta to induce migration by wound healing and transwell invasion assays in human gastric cancer cell lines. miRNA expression was altered using miRNA-181b mimic and inhibitor in the same system. Expression of miRNA 181b, the hypothetical target gene Timp3 and EMT-related markers were analyzed by real-time real-time quantitative RT-PCR. Immunoblotting was used to investigate the levels of phospho-Smad2 and Smad4. Dual-luciferase reporter assays were performed to confirm the direct binding of miRNA-181b to Timp3. RESULTS: miRNA 181b was significantly upregulated in response to TGF-beta treatment in gastric cancer cell lines. Overexpression of miR-181b mimic induced an in vitro EMT-like change to a phenotype similar to that following TGF-beta treatment alone and was reversed by miRNA-181b inhibitor. Inhibition of TGF-beta-Smad2/3 signaling with SD-208 significantly attenuated the upregulation of miRNA-181b. Knockdown of Smad4 in gastric cancer cells strongly attenuated the upregulation of miRNA-181b. Moreover, miR-181b was found to directly target the 3' untranslated region (3'UTR) of Timp3 mRNA affecting TGF-beta-induced EMT. CONCLUSIONS: Our results elucidate a novel mechanism through which the TGF-beta pathway regulates the EMT of gastric cancer cells by increasing the levels of miRNA-181b to target Timp3 via the Smad2/3/4-dependent pathway. These findings provide insights into the cellular and environmental factors regulating EMT, which may guide future studies on therapeutic strategies targeting these cells. PMID- 27383204 TI - The farnesoid-X-receptor in myeloid cells controls CNS autoimmunity in an IL-10 dependent fashion. AB - Innate immune responses by myeloid cells decisively contribute to perpetuation of central nervous system (CNS) autoimmunity and their pharmacologic modulation represents a promising strategy to prevent disease progression in Multiple Sclerosis (MS). Based on our observation that peripheral immune cells from relapsing-remitting and primary progressive MS patients exhibited strongly decreased levels of the bile acid receptor FXR (farnesoid-X-receptor, NR1H4), we evaluated its potential relevance as therapeutic target for control of established CNS autoimmunity. Pharmacological FXR activation promoted generation of anti-inflammatory macrophages characterized by arginase-1, increased IL-10 production, and suppression of T cell responses. In mice, FXR activation ameliorated CNS autoimmunity in an IL-10-dependent fashion and even suppressed advanced clinical disease upon therapeutic administration. In analogy to rodents, pharmacological FXR activation in human monocytes from healthy controls and MS patients induced an anti-inflammatory phenotype with suppressive properties including control of effector T cell proliferation. We therefore, propose an important role of FXR in control of T cell-mediated autoimmunity by promoting anti-inflammatory macrophage responses. PMID- 27383205 TI - Incorporation of Farnesol Significantly Increases the Efficacy of Liposomal Ciprofloxacin against Pseudomonas aeruginosa Biofilms in Vitro. AB - The challenge of eliminating Pseudomonas aeruginosa infections, such as in cystic fibrosis lungs, remains unchanged due to the rapid development of antibiotic resistance. Poor drug penetration into dense P. aeruginosa biofilms plays a vital role in ineffective clearance of the infection. Thus, the current antibiotic therapy against P. aeruginosa biofilms need to be revisited and alternative antibiofilm strategies need to be invented. Fungal quorum sensing molecule (QSM), farnesol, appears to have detrimental effects on P. aeruginosa. Thus, this study aimed to codeliver naturally occurring QSM farnesol, with the antibiotic ciprofloxacin as a liposomal formulation to eradicate P. aeruginosa biofilms. Four different liposomes (with ciprofloxacin and farnesol, Lcip+far; with ciprofloxacin, Lcip; with farnesol, Lfar; control, Lcon) were prepared using dehydration-rehydration method and characterized. Drug entrapment and release were evaluated by spectrometry and high performance liquid chromatography (HPLC). The efficacy of liposomes was assessed using standard biofilm assay. Liposome treated 24 h P. aeruginosa biofilms were quantitatively assessed by XTT reduction assay and crystal violet assay, and qualitatively by confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM). Ciprofloxacin release from liposomes was higher when encapsulated with farnesol (Lcip+far) compared to Lcip (3.06% vs 1.48%), whereas farnesol release was lower when encapsulated with ciprofloxacin (Lcip+far) compared to Lfar (1.81% vs 4.75%). The biofilm metabolism was significantly lower when treated with Lcip+far or Lcip compared to free ciprofloxacin (XTT, P < 0.05). When administered as Lcip+far, the ciprofloxacin concentration required to achieve similar biofilm inhibition was 125-fold or 10-fold lower compared to free ciprofloxacin or Lcip, respectively (P < 0.05). CLSM and TEM confirmed predominant biofilm disruption, greater dead cell ratio, and increased depth of biofilm killing when treated with Lcip+far compared to other liposomal preparations. Thus, codelivery of farnesol and ciprofloxacin is likely to be a promising approach to battle antibiotic resistant P. aeruginosa biofilms by enhancing biofilm killing at significantly lower antibiotic doses. PMID- 27383206 TI - The first complete sequence and genome structure of daphne virus Y. AB - From Daphne odora Thunb., an ornamental shrub in the Republic of Korea, a potyvirus was identified that has an RNA genome of 9,448 nucleotides (excluding the 3'-terminal poly(A) tail) encoding a polyprotein of 3,065 amino acids, with nine putative protease cleavage sites producing ten proteins. Since this potyvirus shared the highest nucleotide sequence identity (91 %; query coverage 5 %) with the available partial sequence of daphne virus Y (DVY) from New Zealand (EU179854), it was considered a Korean isolate of DVY. This is the first molecular characterization of the complete genome sequence of a DVY isolate. PMID- 27383207 TI - Hepatitis B virus infection in blood donors in Argentina: prevalence of infection, genotype distribution and frequency of occult HBV infection. AB - This study describes the prevalence of HBV infection based on detection of HBsAg and HBV-DNA by NAT in 70,102 blood donors in Argentina (Cordoba province) and shows the viral genotype distribution and frequency of occult HBV infection (OBI) in this population. Forty-two donors were confirmed positive for HBV infection (0.06 %), and four had OBI. Genotype F was the most prevalent (71.4 %), followed by A (14.3 %), C (7.1 %) and D (7.1 %). This is the first report of the prevalence of confirmed HBV infection and the high frequency of occult HBV infection in a blood bank in Argentina. PMID- 27383208 TI - The amino-terminal domain of ORF149 of koi herpesvirus is preferentially targeted by IgM from carp populations surviving infection. AB - Recombinantly expressed fragments of the protein encoded by ORF149 (pORF149), a structural protein from the common- and koi-carp-infecting cyprinid herpesvirus-3 (CyHV-3) that was previously shown to be antigenic, were used to obtain evidence that its amino-terminal part contains immunodominant epitopes in fish populations that survived the infection. To obtain such evidence, nonspecific binding of carp serum tetrameric IgM had to be overcome by a novel ELISA protocol (rec2-ELISA). Rec2-ELISA involved pre-adsorption of carp sera with a heterologous recombinant fragment before incubation with pORF149 fragments and detection with anti-carp IgM monoclonal antibodies. Only in this way was it possible to distinguish between sera from uninfected and survivor carp populations. Although IgM from survivors recognised pORF149 fragments to a lesser degree than whole virus, specificity was confirmed by correlation of rec2- and CyHV-3-ELISAs, inhibition of rec2-ELISA by an excess of frgIIORF149, ELISA using IgM-capture, Western blotting, and reduction of reactivity in CyHV-3-ELISA by pre-adsorption of sera with frgIIORF149. The similarity of IgM-binding profiles between frgIORF149 (amino acid residues 42-629) and frgIIORF149 (42-159) and their reactivities with previously described anti-CyHV-3 monoclonal antibodies confirmed that most pORF149 epitopes were localised in its amino-terminal part. PMID- 27383209 TI - Genetic characterization of influenza A virus subtypes H1N3 and H1N9 isolated from free-grazing ducks in Thailand. AB - Influenza A virus (IAV) subtype H1 has been reported to infect birds, pigs and humans. In this study, we characterized IAVs subtype H1N3 and H1N9 isolated from free-grazing ducks in Thailand. Phylogenetic analysis showed that Thai IAV-H1 isolates cluster with avian Eurasian-lineage but not pandemic H1N1 viruses. Analysis of the viruses indicated low-pathogenic avian influenza (LPAI) characteristics. This study is the first report of avian H1N3 and H1N9 in Thailand. Although Thai IAV-H1 viruses do not pose a risk of a pandemic, routine surveillance and genetic monitoring of IAVs should be conducted. PMID- 27383210 TI - Double-stranded-RNA-specific adenosine deaminase 1 (ADAR1) is proposed to contribute to the adaptation of equine infectious anemia virus from horses to donkeys. AB - Equine infectious anemia virus (EIAV) is a member of the genus Lentivirus of the family Retroviridae. Horses are the most susceptible equids to EIAV infection and are therefore the primary hosts of this virus. In contrast, infected donkeys do not develop clinically active equine infectious anemia (EIA). This phenomenon is similar to what has been observed with HIV-1, which fails to induce AIDS in non human primates. Interestingly, Shen et al. developed a donkey-tropic pathogenic virus strain (EIAVDV117, DV117) by serially passaging a horse-tropic pathogenic strain, EIAVLN40 (LN40), in donkeys. LN40, which was generated by passaging a field isolate in horses, displayed enhanced virulence in horses but caused no clinical symptoms in donkeys. Infection with DV117 induced acute EIA in nearly 100 % of donkeys. Genomic analysis of DV117 revealed a significantly higher frequency of A-to-G substitutions when compared to LN40. Furthermore, detailed analysis of dinucleotide editing showed that A-to-G mutations had a preference for 5'TpA and 5'ApA. These results strongly implicated the activity of the adenosine deaminase, ADAR1, in this type of mutation. Further investigation demonstrated that overexpression of donkey ADAR1 increased A-to-G mutations within the genome of EIAV. Together with our previous finding that multiple mutations in multiple genes are generated in DV117 during its adaptation from horses to donkeys, the present study suggests that ADAR1-induced A-to-G mutations occur during virus adaption to related new hosts contributing to the alteration of EIAV host tropism. PMID- 27383211 TI - A Quantitative Analysis of Pulsed Signals Emitted by Wild Bottlenose Dolphins. AB - Common bottlenose dolphins (Tursiops truncatus), produce a wide variety of vocal emissions for communication and echolocation, of which the pulsed repertoire has been the most difficult to categorize. Packets of high repetition, broadband pulses are still largely reported under a general designation of burst-pulses, and traditional attempts to classify these emissions rely mainly in their aural characteristics and in graphical aspects of spectrograms. Here, we present a quantitative analysis of pulsed signals emitted by wild bottlenose dolphins, in the Sado estuary, Portugal (2011-2014), and test the reliability of a traditional classification approach. Acoustic parameters (minimum frequency, maximum frequency, peak frequency, duration, repetition rate and inter-click-interval) were extracted from 930 pulsed signals, previously categorized using a traditional approach. Discriminant function analysis revealed a high reliability of the traditional classification approach (93.5% of pulsed signals were consistently assigned to their aurally based categories). According to the discriminant function analysis (Wilk's Lambda = 0.11, F3, 2.41 = 282.75, P < 0.001), repetition rate is the feature that best enables the discrimination of different pulsed signals (structure coefficient = 0.98). Classification using hierarchical cluster analysis led to a similar categorization pattern: two main signal types with distinct magnitudes of repetition rate were clustered into five groups. The pulsed signals, here described, present significant differences in their time-frequency features, especially repetition rate (P < 0.001), inter click-interval (P < 0.001) and duration (P < 0.001). We document the occurrence of a distinct signal type-short burst-pulses, and highlight the existence of a diverse repertoire of pulsed vocalizations emitted in graded sequences. The use of quantitative analysis of pulsed signals is essential to improve classifications and to better assess the contexts of emission, geographic variation and the functional significance of pulsed signals. PMID- 27383212 TI - A Bioorthogonal Approach for the Preparation of a Titanium-Binding Insulin-like Growth-Factor-1 Derivative by Using Tyrosinase. AB - The generation of metal surfaces with biological properties, such as cell-growth enhancing and differentiation-inducing abilities, could be potentially exciting for the development of functional materials for use in humans, including artificial dental implants and joint replacements. However, currently the immobilization of proteins on the surfaces of the metals are limited. In this study, we have used a mussel-inspired bioorthogonal approach to design a 3,4 hydroxyphenalyalanine-containing recombinant insulin-like growth-factor-1 using a combination of recombinant DNA technology and tyrosinase treatment for the surface modification of titanium. The modified growth factor prepared in this study exhibited strong binding affinity to titanium, and significantly enhanced the growth of NIH3T3 cells on the surface of titanium. PMID- 27383213 TI - Balance between cAMP and Ca(2+) signals regulates expression levels of pituitary adenylate cyclase-activating polypeptide gene in neurons. AB - Mice lacking the gene encoding pituitary adenylate cyclase-activating polypeptide (PACAP) or its specific receptor, PAC1, show abnormal behaviors related to schizophrenia. However, the regulation of PACAP expression in neurons remains unclear. Here, we report that Pacap mRNA levels are regulated transcriptionally and post-transcriptionally by cAMP and Ca(2+) signals in cultured rat cortical cells. Pacap mRNA levels decreased proportionately with the intensity of cAMP signaling, and this decrease was accelerated by N-methyl-D-aspartate (NMDA) receptor blockade, suggesting that cAMP signaling enhances the degradation of Pacap mRNA, whereas NMDA receptor-mediated signals inhibit its degradation. However, depolarization (which produced a robust increase in Ca(2+) signals) together with cAMP signaling resulted in a synergistic induction of Pacap mRNA through calcineurin and its substrate, cAMP-response element-binding protein (CREB)-regulated transcription coactivator 1. These results strongly support the concept that while cAMP signaling can accelerate the degradation of Pacap mRNA, it can also synergistically enhance Ca(2+) signaling-induced transcriptional activation of Pacap. Taken together, our findings suggest that a balance between Ca(2+) and cAMP signals regulates PACAP levels in neurons and that a perturbation of this balance may result in psychiatric disorders, such as schizophrenia. PMID- 27383214 TI - Ablative Focused Ultrasound Synergistically Enhances Thermally Triggered Chemotherapy for Prostate Cancer in Vitro. AB - High-intensity focused ultrasound (HIFU) can locally ablate biological tissues such as tumors, i.e., induce their rapid heating and coagulative necrosis without causing damage to surrounding healthy structures. It is widely used in clinical practice for minimally invasive treatment of prostate cancer. Nonablative, low power HIFU was established as a promising tool for triggering the release of chemotherapeutic drugs from temperature-sensitive liposomes (TSLs). In this study, we combine ablative HIFU and thermally triggered chemotherapy to address the lack of safe and effective treatment options for elderly patients with high risk localized prostate cancer. DU145 prostate cancer cells were exposed to chemotherapy (free and liposomal Sorafenib) and ablative HIFU, alone or in combination. Prior to cell viability assessment by trypan blue exclusion and flow cytometry, the uptake of TSLs by DU145 cells was verified by confocal microscopy and cryogenic scanning electron microscopy (cryo-SEM). The combination of TSLs encapsulating 10 MUM Sorafenib and 8.7W HIFU resulted in a viability of less than 10% at 72 h post-treatment, which was significant less than the viability of the cells treated with free Sorafenib (76%), Sorafenib-loaded TSLs (63%), or HIFU alone (44%). This synergy was not observed on cells treated with Sorafenib-loaded nontemperature sensitive liposomes and HIFU. According to cryo-SEM analysis, cells exposed to ablative HIFU exhibited significant mechanical disruption. Water bath immersion experiments also showed an important role of mechanical effects in the synergistic enhancement of TSL-mediated chemotherapy by ablative HIFU. This combination therapy can be an effective strategy for treatment of geriatric prostate cancer patients. PMID- 27383216 TI - Influence of Four Radiotracers in PET/CT on Diagnostic Accuracy for Prostate Cancer: A Bivariate Random-Effects Meta-Analysis. AB - BACKGROUND/AIMS: To date, several positron emission tomography/computed tomography (PET/CT) radiotracers including fluorine-18 fluorodeoxyglucose (18F FDG), carbon-11 labeled choline (11C-choline), 18-F fluorocholine (18F-FCH) and carbon-11 acetate (11C-acetate) have already been assessed in the application of prostate cancer (PCa) diagnosis to some extent, the diagnostic efficiency of these radiotracers still remain controversial. As a result of this, we carried out this meta-analysis for the purpose of comparing the diagnostic accuracy among four PET/CT radiotracers. METHODS: A systematical literature search for articles was performed until July 3, 2015. We implemented all analysis using the statistical software of STATA12 and quality assessment was performed using QUADAS 2. RESULTS: A total of 56 studies containing 3,586 patients were included in this meta-analysis. Parameter estimates of the overall analysis are as follows: sensitivity, 0.80 (95% CI: 0.74-0.85); specificity, 0.84 (95% CI: 0.77-0.89) and area under roc curve-AUC of SROC, 0.89 (95% CI: 0.86-0.91), indicating a relatively high level of accuracy in diagnosis of PCa. When different radiotracers of PET/CT were compared, 18F-FCH-PET/CT was ranked as the most favorable with the highest value of AUC (AUC = 0.94; 95% CI: 0.92-0.96) whereas 18F-FDG was the least favorable (AUC = 0.73, 95% CI: 0.69-0.77). CONCLUSION: This study suggested that PET/CT imaging plays an invaluable role in the diagnosis of PCa and 18F-FCH-PET/CT was considered as a superior diagnostic tool over other radiotracers. More attention should be paid to the diagnostic efficiency of the four radiotracers particularly for PCa patients with different clinical stages. PMID- 27383215 TI - Type 2 Diabetes Risk Allele Loci in the Qatari Population. AB - BACKGROUND: The prevalence of type 2 diabetes (T2D) is increasing in the Middle East. However, the genetic risk factors for T2D in the Middle Eastern populations are not known, as the majority of studies of genetic risk for T2D are in Europeans and Asians. METHODS: All subjects were >=3 generation Qataris. Cases with T2D (n = 1,124) and controls (n = 590) were randomly recruited and assigned to the 3 known Qatari genetic subpopulations [Bedouin (Q1), Persian/South Asian (Q2) and African (Q3)]. Subjects underwent genotyping for 37 single nucleotide polymorphisms (SNPs) in 29 genes known to be associated with T2D in Europeans and/or Asian populations, and an additional 27 tag SNPs related to these susceptibility loci. Pre-study power analysis suggested that with the known incidence of T2D in adult Qataris (22%), the study population size would be sufficient to detect significant differences if the SNPs were risk factors among Qataris, assuming that the odds ratio (OR) for T2D SNPs in Qatari's is greater than or equal to the SNP with highest known OR in other populations. RESULTS: Haplotype analysis demonstrated that Qatari haplotypes in the region of known T2D risk alleles in Q1 and Q2 genetic subpopulations were similar to European haplotypes. After Benjamini-Hochberg adjustment for multiple testing, only two SNPs (rs7903146 and rs4506565), both associated with transcription factor 7-like 2 (TCF7L2), achieved statistical significance in the whole study population. When T2D subjects and control subjects were assigned to the known 3 Qatari subpopulations, and analyzed individually and with the Q1 and Q2 genetic subpopulations combined, one of these SNPs (rs4506565) was also significant in the admixed group. No other SNPs associated with T2D in all Qataris or individual genetic subpopulations. CONCLUSIONS: With the caveats of the power analysis, the European/Asian T2D SNPs do not contribute significantly to the high prevalence of T2D in the Qatari population, suggesting that the genetic risks for T2D are likely different in Qataris compared to Europeans and Asians. PMID- 27383217 TI - Twenty-Eight-Day Mortality of Blunt Traumatic Brain Injury and Co-Injuries Requiring Mechanical Ventilation. AB - OBJECTIVE: This paper aims to assess the impact of co-injuries and consequent emergency surgical interventions and nosocomial pneumonia on the 28-day mortality of patients with severe traumatic brain injuries (TBIs). SUBJECTS AND METHODS: One hundred and seventy-seven patients with TBI admitted to the emergency trauma intensive care unit at the Clinical Center of Serbia for more than 48 h were studied over a 1-year period. On admission, the Glasgow Coma Scale (GCS), Injury Severity Score (ISS) and Acute Physiology and Chronic Health Evaluation II score (APACHE II) were calculated. At admission, an isolated TBI was recorded in 45 of the patients, while 44 had three or more co-injuries. RESULTS: Of the 177 patients, 78 (44.1%) died by the end of the 28-day follow-up period. They had a significantly higher ISS score (25 vs. 20; p = 0.024) and more severe head (p = 0.034) and chest (p = 0.013) injuries compared to those who survived. Nonsurvivors had spent more days on mechanical ventilation (9.5 vs. 8; p = 0.041) and had a significantly higher incidence of ventilator-associated pneumonia (VAP) than survivors (67.9 vs. 40.4%; p < 0.001). A high Rotterdam CT score (OR 2.062; p < 0.001) and a high APACHE II score (OR 1.219; p < 0.001) were identified as independent predictors of early TBI-related mortality. CONCLUSION: Patients who had TBI with a high Rotterdam score and a high APACHE II score were at higher risk of 28-day mortality. VAP was a very common complication of TBI and was associated with an early death and higher mortality in the subgroup of patients with a GCS <=8. PMID- 27383219 TI - Systemic effects of low-dose dopamine during administration of cytarabine. AB - Purpose Low-dose dopamine has been utilized to improve renal blood flow, urine output, and reduce drug-induced nephrotoxicity. The purpose of this study was to assess changes in renal function, cardiovascular adverse events, and neurologic toxicity in patients receiving cytarabine with or without low-dose dopamine. Methods A retrospective, single-center, cohort study of patients receiving cytarabine at 667 mg/m2/dose or greater, with or without dopamine at <=5 mcg/kg/min. Cohorts were based upon initiation or absence of low-dose dopamine; cytarabine only, cytarabine + pre- and day of low-dose dopamine, and cytarabine + post-low-dose dopamine. Renal outcomes (urine output, serum creatinine, and creatinine clearance) were compared with baseline and between cohorts. Safety endpoints (arrhythmias, tachycardia, and neurotoxicity) were compared between cohorts based on low-dose dopamine exposure. Results There was no difference in urine output from baseline in all cohorts. Comparing cytarabine only and pre- and day of low-dose dopamine cohorts, there was no difference in urine output. In those receiving low-dose dopamine, there was no difference in serum creatinine and creatinine clearance from baseline. No arrhythmias were documented during the study period, and there was no difference in the incidence of tachycardia between groups (P = 0.66). Neurotoxicity was reported in three patients who were on low dose dopamine. Conclusion Though variation existed in individual patients administered low-dose dopamine, the use of low-dose dopamine did not significantly impact renal function in this small sample at a single institution. In addition, low-dose dopamine did not negatively impact cardiovascular function. PMID- 27383218 TI - Failed treatment of long bone nonunions with low intensity pulsed ultrasound. AB - INTRODUCTION: The use of low intensity pulsed ultrasound (LIPUS) in the treatment of nonunions is still controversial. The present study is concerned with whether this procedure has a clinical use and which cofactors influence its therapeutic results. METHODS: In this prospective, single institution, observational study, data from October 2010 to October 2013 from 61 nonunions in 60 patients treated with EXOGEN((r)) LIPUS therapy were analysed. The average age was 45.4 +/- 9.81 (18-63) years. Treatment was primarily done on long bones of the lower extremity (75.4 %). All 61 nonunions were examined after treatment, and the rate of healing as well as functional and subjective results were evaluated. Based on clinical and radiological findings, patients were divided into two groups: G1-successful treatment; and G2-unsuccessful treatment. Groups were compared to one another to identify possible factors influencing treatment. RESULTS: Twenty (32.8 %) patients showed bone consolidation with an average time of healing of 5.3 (2-7) months. In patients without successful treatment, who underwent revision surgery instead, full weight bearing took on average 3.7 months longer, and they were able to return to work 6.8 months later. Most of the treated patients (70.5 %) reported no improvement in pain. In G2, 12 (29.3 %) patients suffered in their previous history from osteitis; in G1 there were only two patients (10 %) (p = 0.012). There were further significant differences in the age of the fracture, the type of osteosynthesis, the gap size, as well as the NUSS score. CONCLUSION: Despite patients being chosen strictly according to EXOGEN((r)) indications, only a small number of patients with nonunions who underwent LIPUS therapy experienced successful treatment (32.8 %). Overall, its use resulted in a clear delay in the time of treatment, so that according to our results, the use of LIPUS should be seen critically in long bone nonunions and use should be made on a case-by-case basis. PMID- 27383220 TI - A rare cause of temple syndrome. PMID- 27383222 TI - Emotional intelligence and job performance: The mediating role of work-family balance. AB - In this study, we examine the dynamics between emotional intelligence, work family balance, and job performance. A review of the literature to date has shown distinct relationships between emotional intelligence to job performance and work family balance to job performance. We utilize a sample of 233 respondents to empirically test our set of hypotheses that contend work-family balance mediates the relationship between emotional intelligence and job performance. Our results support these hypotheses. Practical implications and directions for future research are discussed. PMID- 27383223 TI - Controlled capillary assembly of magnetic Janus particles at fluid-fluid interfaces. AB - Capillary interactions can be used to direct assembly of particles adsorbed at fluid-fluid interfaces. Precisely controlling the magnitude and direction of capillary interactions to assemble particles into favoured structures for materials science purposes is desirable but challenging. In this paper, we investigate capillary interactions between magnetic Janus particles adsorbed at fluid-fluid interfaces. We develop a pair-interaction model that predicts that these particles should arrange into a side-side configuration, and carry out simulations that confirm the predictions of our model. Finally, we investigate the monolayer structures that form when many magnetic Janus particles adsorb at the interface. We find that the particles arrange into long, straight chains exhibiting little curvature, in contrast with capillary interactions between ellipsoidal particles. We further find a regime in which highly ordered, lattice like monolayer structures form, which can be tuned dynamically using an external magnetic field. PMID- 27383221 TI - Glycogen: A must have storage to survive stressful emergencies. AB - Mechanisms of adaptation to acute changes in osmolarity are fundamental for life. When exposed to hyperosmotic stress, cells and organisms utilize conserved strategies to prevent water loss and maintain cellular integrity and viability. The production of glycerol is a common strategy utilized by the nematode Caenorhabditis elegans (C. elegans) and many other organisms to survive hyperosmotic stress. Specifically, the transcriptional upregulation of glycerol-3 phosphate dehydrogenase, a rate-limiting enzyme in the production of glycerol, has been previously implicated in many model organisms. However, what fuels this massive and rapid production of glycerol upon hyperosmotic stress has not been clearly elucidated. We have recently discovered an AMPK-dependent pathway that mediates hyperosmotic stress resistance in C. elegans. Specifically, we demonstrated that the chronic activation of AMPK leads to glycogen accumulation, which under hyperosmotic stress exposure, is rapidly degraded to mediate glycerol production. Importantly, we demonstrate that this strategy is utilized by flcn-1 mutant C. elegans nematodes in an AMPK-dependent manner. FLCN-1 is the worm homolog of the human renal tumor suppressor Folliculin (FLCN) responsible for the Birt-Hogg-Dube neoplastic syndrome. Here, we comment on the dual role for glycogen in stress resistance: it serves as an energy store and a fuel for osmolyte production. We further discuss the potential utilization of this mechanism by organisms in general and by human cancer cells in order to survive harsh environmental conditions and notably hyperosmotic stress. PMID- 27383224 TI - The use of conjunctions by children with typical language development. AB - PURPOSE: To investigate the use of conjunctions in the spontaneous speech of three years old children with typical language development, who live in Santa Maria - RS. METHODS: 45 children, aged 3:0;0 - 3:11;29 (years:months;days) from the database of the Center for the Study of Language and Speech (CELF) participated of this study. The spontaneous speech of each child was transcribed and followed by analysis of the samples to identify the types of conjunctions for each age group. The samples were statistically analyzed using the R software that allowed the evaluation of the number and type of conjunctions used in each age group by comparing them with each other. RESULTS: The data indicated that the higher the age of the child, the greater the number of types of conjunctions used by them. The comparison between age groups showed significant differences when comparing the average number of conjunctions per age group, as well as for additive conjunctions and subordinating conjunctions. CONCLUSION: At age of three the children begin to develop the grammatical use of conjunctions, early appearing additive, adversative and explanatory coordinating conjunctions, and at 3:6 they are able to use the most complex conjunctions, as subordinating conjunctions. PMID- 27383225 TI - Self-assessment and readiness for change in dysphonic patients. AB - PURPOSE: To examine whether there is an association between vocal self-assessment and readiness for change in dysphonic patients. METHODS: 151 patients with vocal complaints and diagnosis of dysphonia, between 18 and 65 years of age, 47 men and 104 women treated at the voice clinic of a public institution participated in the study. Four self-assessment instruments were applied, including the Voice-Related Quality of Life (V-RQOL), the Voice Handicap Index (VHI) and the Voice Symptom Scale (VoiSS), and the use of URICA-VOICE instrument to verify the patients stage of readiness for change. All instruments were applied immediately before the start of vocal therapy. The variables were correlated and compared using inferential statistics. RESULTS: Most patients were in the contemplation stage (76.2%, n = 115), 22 (14.6%) were in the pre-contemplation stage and 14 (9.3%) in the action stage. There was a negative correlation between the score in URICA VOICE and the socio-emotional domain and total score V-RQOL. There was a positive correlation between the score URICA-VOICE and full social, emotional and functional VHI, as well as between the score URICA-VOICE and full fields, limitation and emotional VoiSS. Only the social-emotional domain V-RQOL and emotional in VoiSS values showed statistically significant differences between the motivational stages. CONCLUSION: There is association between vocal self assessment and readiness for change in dysphonic patients. Patients with major impact on quality of life in voice in V-RQOL and higher frequency of vocal symptoms mentioned in the VoiSS show greater readiness for change. PMID- 27383226 TI - Assessment for oral feeding in preterm infants. AB - PURPOSE: To assess the accuracy of the Preterm Oral Feeding Readiness Scale (POFRAS) on the beginning of oral feeding in preterm infants and to verify the concordance between this tool and the Oral Feeding Skill Level. METHODS: 82 preterm infants were assessed by POFRAS regarding their readiness to initiate oral feeding and by the oral feeding skill level evaluation during the first oral feeding. POFRAS's accuracy was estimated regarding proficiency by a Receiver Operating Characteristics (ROC) curve. The concordance between the tools was obtained by analysis of the Kappa coefficient. RESULTS: POFRAS's global accuracy was of 71.29%. The cut-off value of 29 was the one that presented most optimization of the sensitivity based on specificity. The Kappa coefficient has shown a weak concordance between the instruments to identify infants able and unable to oral feeding (k=0.281). CONCLUSION: POFRAS's accuracy to initiate oral feeding considering the proficiency was similar to that obtained with the technique of translactation. We observed a weak concordance between the instruments. We suggest that, in clinical practice, both instruments should be used in a complementary manner, since both present important aspects of the preterm feeding behavior that together will better guide the necessary conduct to provide an effective and quick transition to full oral feeding in this population. PMID- 27383227 TI - Stuttering at school: the effect of a teacher training program on stuttering. AB - PURPOSE: Verify the knowledge of teachers from public and private schools about stuttering and attest the effectiveness of the Teacher Training Program on Stuttering in the expansion of this knowledge. METHODS: The study sample comprised 137 early-childhood teachers. Initially, the teachers responded to a questionnaire on stuttering. After that, 75 teachers attended a 4-hour Teacher Training Program on Stuttering. One month later, the teachers responded to the same questionnaire again. RESULTS: The following points were observed after the training program: increased percentage of teachers who consider as low the prevalence of stuttering in the population; beginning of reports stating that stuttering is more frequent in males; increased number of teachers who consider stuttering hereditary; decreased incidence of teachers who believe stuttering is psychological; prevalence of those who believe stuttering is a consequence of multiple causes; decreased rate of teachers who believe stuttering is emotional; a better understanding of how educators should behave to help stutterers. CONCLUSION: Before the course, the teachers had some knowledge regarding stuttering, but it was insufficient to differentiate from other language disorders. The Program expanded their knowledge on stuttering. However, it proved to be more effective with respect to the characteristics of stuttering than to the attitudes of the teachers. PMID- 27383228 TI - Nasalance values for syllables produced by Brazilian Portuguese speakers. AB - PURPOSE: This study aimed to determine nasalance values for syllables produced by Brazilian Portuguese speakers of different ages and gender. METHODS: Nasalance scores were collected for 14 syllables (10 orals and 4 nasals) using Nasometer II 6400. The participants were 245 Brazilian Portuguese speakers (121 males and 124 females), both genders, divided into four age groups: 57 children, 61 adolescents, 65 young adults and 62 adults. RESULTS: Nasalance scores for nasal syllables were higher than for oral syllables. For both, oral and nasal syllables, nasalance scores were higher for vowel /i/ than for /a/. Across all syllables, the females' nasalance scores were higher than males, with most of this difference attributed to the oldest age group where females mean nasalance was three points higher than males. CONCLUSION: Values obtained demonstrated nasalance scores variation according to gender, particularly for the adult group and for the syllables tested. PMID- 27383229 TI - Errata. AB - The Figure 1 printed on p. 1176 on Vol. 64, June, 2000 is in correct (LEFT). The correct figure is shown below (RIGHT). Printer's error. PMID- 27383230 TI - Cryopreservation of Human Adipose-Derived Stem Cells in Combination with Trehalose and Reversible Electroporation. AB - New cryopreservation approaches for medically applicable cells are of great importance in clinical medicine. Current protocols employ the use of dimethyl sulfoxide (DMSO), which is toxic to cells and causes undesirable side effects in patients, such as cardiac arrhythmias, neurological events, and others. Trehalose, a nontoxic disaccharide, has been already studied as a cryoprotectant. However, an efficient approach for loading this impermeable sugar into mammalian cells is missing. In our study, we assessed the efficiency of combining reversible electroporation and trehalose for cryopreservation of human adipose derived stem cells. First, we determined reversible electroporation threshold by loading of propidium iodide into cells. The highest permeabilization while maintaining high cell viability was reached at 1.5 kV/cm, at 8 pulses, 100 us, and 1 Hz. Second, cells were incubated in 250 or 400 mM trehalose and electroporated before cryopreservation. After thawing, 83.8 +/- 1.8 % (mean +/- SE) cell recovery was obtained at 250 mM trehalose. By using a standard freezing protocol (10 % DMSO in 90 % fetal bovine serum), cell survival after thawing was about 91.5 +/- 1.6 %. We also evaluated possible effects of electroporation on cells' functionality before and after thawing. Successful cell growth and efficient adipogenic and osteogenic differentiation were achieved. In conclusion, electroporation seems to be an efficient method for loading nonpermeable trehalose into human adipose-derived stem cells, allowing long-term cryopreservation in DMSO-free and xeno-free conditions. PMID- 27383231 TI - Resonance Raman spectroscopic study of the interaction between Co(II)rrinoids and the ATP:corrinoid adenosyltransferase PduO from Lactobacillus reuteri. AB - The human-type ATP:corrinoid adenosyltransferase PduO from Lactobacillus reuteri (LrPduO) catalyzes the adenosylation of Co(II)rrinoids to generate adenosylcobalamin (AdoCbl) or adenosylcobinamide (AdoCbi(+)). This process requires the formation of "supernucleophilic" Co(I)rrinoid intermediates in the enzyme active site which are properly positioned to abstract the adeonsyl moiety from co-substrate ATP. Previous magnetic circular dichroism (MCD) spectroscopic and X-ray crystallographic analyses revealed that LrPduO achieves the thermodynamically challenging reduction of Co(II)rrinoids by displacing the axial ligand with a non-coordinating phenylalanine residue to produce a four-coordinate species. However, relatively little is currently known about the interaction between the tetradentate equatorial ligand of Co(II)rrinoids (the corrin ring) and the enzyme active site. To address this issue, we have collected resonance Raman (rR) data of Co(II)rrinoids free in solution and bound to the LrPduO active site. The relevant resonance-enhanced vibrational features of the free Co(II)rrinoids are assigned on the basis of rR intensity calculations using density functional theory to establish a suitable framework for interpreting rR spectral changes that occur upon Co(II)rrinoid binding to the LrPduO/ATP complex in terms of structural perturbations of the corrin ring. To complement our rR data, we have also obtained MCD spectra of Co(II)rrinoids bound to LrPduO complexed with the ATP analogue UTP. Collectively, our results provide compelling evidence that in the LrPduO active site, the corrin ring of Co(II)rrinoids is firmly locked in place by several amino acid side chains so as to facilitate the dissociation of the axial ligand. PMID- 27383232 TI - An unusual association of three autoimmune disorders: celiac disease, systemic lupus erythematosus and Hashimoto's thyroiditis. AB - Autoimmune disorders are known to be more frequent in women and often associated each others, but it is rare to see multiple autoimmune diseases in a single patient. Recently, the concept of multiple autoimmune syndrome has been introduced to describe patients with at least three autoimmune diseases. We describe a case of a young man with a clinical history of psychiatric symptoms and celiac disease (CD) who was diagnosed to have other two autoimmune disorders: systemic lupus erythematosus (SLE) and Hashimoto's thyroiditis. This case is unusual upon different patterns: the rare combination of the three autoimmune diseases, their appearance in a man and the atypical onset of the diseases with psychiatric symptoms likely to be related either to CD or to SLE. PMID- 27383233 TI - The RNA binding protein HuR determines the differential translation of autism associated FoxP subfamily members in the developing neocortex. AB - Forkhead-box domain (Fox) containing family members are known to play a role in neocorticogenesis and have also been associated with disorders on the autism spectrum. Here we show that a single RNA-binding protein, Hu antigen R (HuR), dictates translation specificity of bound mRNAs and is sufficient to define distinct Foxp-characterized subpopulations of neocortical projection neurons. Furthermore, distinct phosphorylation states of HuR differentially regulate translation of Foxp mRNAs in vitro. This demonstrates the importance of RNA binding proteins within the framework of the developing brain and further confirms the role of mRNA translation in autism pathogenesis. PMID- 27383234 TI - Efficient and Targeted Suppression of Human Lung Tumor Xenografts in Mice with Methotrexate Sodium Encapsulated in All-Function-in-One Chimeric Polymersomes. AB - Anisamide-functionalized reversibly crosslinked chimeric polymersomes emerge as an "all-function-in-one" nanoplatform for efficient loading and targeted delivery of methotrexate disodium, a potent water-soluble anticancer drug, to sigma receptor overexpressing H460 nonsmall lung cancer xenografts in vivo, leading to markedly improved tumor-growth inhibition and survival rate and depleted adverse effects as compared to the clinically used formulation (Trexall). PMID- 27383238 TI - A Typical Metal-Ion-Responsive Color-Tunable Emitting Insulated pi-Conjugated Polymer Film. AB - We report the synthesis of an insulated pi-conjugated polymer containing 2,2' bipyridine moieties as metal coordination sites. Metal coordination to the polymer enabled easy and reversible tuning of the luminescent color without changes to the main chain skeleton. The permethylated alpha-cyclodextrin (PM alpha-CD)-based insulation structure allowed the metalated polymers to demonstrate efficient emission even in the solid state, with identical spectral shapes to the dilute solutions. In addition, the coordination ability of the metal-free polymer was maintained in the solid state, resulting in reversible changes in the luminescent color in response to the metal ions. The synthesized polymer is expected to be suitable for application in recyclable luminescent sensors to distinguish different metal ions. PMID- 27383239 TI - The Effect of Perioperative E-Health Interventions on the Postoperative Course: A Systematic Review of Randomised and Non-Randomised Controlled Trials. AB - BACKGROUND: E-health interventions have become increasingly popular, including in perioperative care. The objective of this study was to evaluate the effect of perioperative e-health interventions on the postoperative course. METHODS: We conducted a systematic review and searched for relevant articles in the PUBMED, EMBASE, CINAHL and COCHRANE databases. Controlled trials written in English, with participants of 18 years and older who underwent any type of surgery and which evaluated any type of e-health intervention by reporting patient-related outcome measures focusing on the period after surgery, were included. Data of all included studies were extracted and study quality was assessed by using the Downs and Black scoring system. FINDINGS: A total of 33 articles were included, reporting on 27 unique studies. Most studies were judged as having a medium risk of bias (n = 13), 11 as a low risk of bias, and three as high risk of bias studies. Most studies included patients undergoing cardiac (n = 9) or orthopedic surgery (n = 7). All studies focused on replacing (n = 11) or complementing (n = 15) perioperative usual care with some form of care via ICT; one study evaluated both type of interventions. Interventions consisted of an educational or supportive website, telemonitoring, telerehabilitation or teleconsultation. All studies measured patient-related outcomes focusing on the physical, the mental or the general component of recovery. 11 studies (40.7%) reported outcome measures related to the effectiveness of the intervention in terms of health care usage and costs. 25 studies (92.6%) reported at least an equal (n = 8) or positive (n = 17) effect of the e-health intervention compared to usual care. In two studies (7.4%) a positive effect on any outcome was found in favour of the control group. CONCLUSION: Based on this systematic review we conclude that in the majority of the studies e-health leads to similar or improved clinical patient-related outcomes compared to only face to face perioperative care for patients who have undergone various forms of surgery. However, due to the low or moderate quality of many studies, the results should be interpreted with caution. PMID- 27383242 TI - Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab. PMID- 27383241 TI - Real and hypothetical monetary rewards modulate risk taking in the brain. AB - Both real and hypothetical monetary rewards are widely used as reinforcers in risk taking and decision making studies. However, whether real and hypothetical monetary rewards modulate risk taking and decision making in the same manner remains controversial. In this study, we used event-related potentials (ERP) with a balloon analogue risk task (BART) paradigm to examine the effects of real and hypothetical monetary rewards on risk taking in the brain. Behavioral data showed reduced risk taking after negative feedback (money loss) during the BART with real rewards compared to those with hypothetical rewards, suggesting increased loss aversion with real monetary rewards. The ERP data demonstrated a larger feedback-related negativity (FRN) in response to money loss during risk taking with real rewards compared to those with hypothetical rewards, which may reflect greater prediction error or regret emotion after real monetary losses. These findings demonstrate differential effects of real versus hypothetical monetary rewards on risk taking behavior and brain activity, suggesting a caution when drawing conclusions about real choices from hypothetical studies of intended behavior, especially when large rewards are used. The results have implications for future utility of real and hypothetical monetary rewards in studies of risk taking and decision making. PMID- 27383240 TI - Perchlorate Exposure Reduces Primordial Germ Cell Number in Female Threespine Stickleback. AB - Perchlorate is a common aquatic contaminant that has long been known to affect thyroid function in vertebrates, including humans. More recently perchlorate has been shown to affect primordial sexual differentiation in the aquatic model fishes zebrafish and threespine stickleback, but the mechanism has been unclear. Stickleback exposed to perchlorate from fertilization have increased androgen levels in the embryo and disrupted reproductive morphologies as adults, suggesting that perchlorate could disrupt the earliest stages of primordial sexual differentiation when primordial germ cells (PGCs) begin to form the gonad. Female stickleback have three to four times the number of PGCs as males during the first weeks of development. We hypothesized that perchlorate exposure affects primordial sexual differentiation by reducing the number of germ cells in the gonad during an important window of stickleback sex determination at 14-18 days post fertilization (dpf). We tested this hypothesis by quantifying the number of PGCs at 16 dpf in control and 100 mg/L perchlorate-treated male and female stickleback. Perchlorate exposure from the time of fertilization resulted in significantly reduced PGC number only in genotypic females, suggesting that the masculinizing effects of perchlorate observed in adult stickleback may result from early changes to the number of PGCs at a time critical for sex determination. To our knowledge, this is the first evidence of a connection between an endocrine disruptor and reduction in PGC number prior to the first meiosis during sex determination. These findings suggest that a mode of action of perchlorate on adult reproductive phenotypes in vertebrates, including humans, such as altered fecundity and sex reversal or intersex gonads, may stem from early changes to germ cell development. PMID- 27383243 TI - The threat of poor quality antibiotics in increasing antimicrobial resistance. PMID- 27383244 TI - Was there ever a golden age for junior doctors? PMID- 27383245 TI - Erratum to: Breast cancer health promotion in Qatar: a survey of community pharmacists' interests and needs. PMID- 27383246 TI - Medicine shortages in Australia: causes, impact and management strategies in the community setting. AB - Background Medicine shortages are an ongoing global problem. The Therapeutic Goods Administration (TGA) dedicated a website for monitoring of medicine shortages in Australia in May 2014, as part of the Medicine Shortage Information Initiative. This study aimed to explore the views of pharmacists regarding medicine shortages in the community setting and the impact of the TGA website in Australia. Setting Community pharmacies in New South Wales, Australia. Method Twenty semi-structured interviews were conducted with community pharmacists. Data collected were analysed thematically utilising the framework analysis method. Main outcome measure Qualitative analysis conducted using the framework approach. Results Findings clearly indicated that medicine shortages were experienced on a regular basis, but most participants were unaware of the TGA website. Medicine shortages reportedly impacted both pharmacists and consumers; and various workarounds were undertaken to manage the issue. The "price disclosure policy" was found to be a prominent contributing factor in emerging shortages. Suggestions were made for ways to improve the growing occurrence of shortages. Conclusion Overall, the study found that there was a lack of familiarity with the TGA website, despite experiencing regular shortages of medicines in practice. Also highlighted, was the importance of pharmacists prioritising patient care over business decisions. To reduce prescribing of out-of-stock medicines notifying doctors about shortages was also considered important, to allow for early action to be taken at higher levels of the supply chain. Findings of this study may help direct future policy-making around the world, as medicine shortages is a problem shared by healthcare providers in most countries around the world. PMID- 27383247 TI - Human Hunting and Nascent Animal Management at Middle Pre-Pottery Neolithic Yiftah'el, Israel. AB - The current view for the southern Levant is that wild game hunting was replaced by herd management over the course of the Pre-Pottery Neolithic B period, but there is significant debate over the timing, scale and origin of this transition. To date, most relevant studies focus either on wild game exploitation in the periods prior to domestication or on classic markers of domestication of domestic progenitor species over the course of the PPNB. We studied the faunal remains from the 2007-2008 excavations of the Middle PPNB (MPPNB) site of Yiftah'el, Northern Israel. Our analysis included a close examination of the timing and impact of the trade-off between wild game and domestic progenitor taxa that reflects the very beginning of this critical transition in the Mediterranean zone of the southern Levant. Our results reveal a direct trade-off between the intensive hunting of wild ungulates that had been staples for millennia, and domestic progenitor taxa. We suggest that the changes in wild animal use are linked to a region-wide shift in the relationship between humans and domestic progenitor species including goat, pig and cattle. PMID- 27383248 TI - Genetic Variations in Phospholipase C-epsilon 1 (PLCE1) and Susceptibility to Colorectal Cancer Risk. AB - Colorectal cancer (CRC) is the third most common cause of cancer-related mortality and causes almost a million deaths worldwide each year. Genetic and environmental factors have gained importance in CRC as well as other types of cancer due to contribution to development of malignancies. Phosholipase C-epsilon 1 PLCE1 is one of the phospholipase family of enzymes and controls cellular responses leading to cell growth, differentiation and gene expression. Therefore, it was evaluated the effects of PLCE1 variations on developing CRC. Rs2274223 was significantly associated with CRC risk (OR = 2.018) while rs3765524 did not significantly differ (p > 0.05). The findings are the first results of PLCE1 profiles in the Turkish and could provide an understanding of aetiology in CRC. PMID- 27383249 TI - Neuropsychological assessment of refugees: Methodological and cross-cultural barriers. AB - Cross-cultural research in neuropsychological assessment has primarily focused on Hispanic and African American populations. Less is known about the impact of language, culture, education, socioeconomic factors, and life experiences on assessment for other cultural groups. We highlight the methodological and cross cultural barriers encountered at each stage of the neuropsychological assessment of Arabic- and Burmese-speaking refugees, who were culturally and linguistically diverse (CALD). A total of 18 refugees (13 men/five women; in their 20-50s) who were victims of torture in their countries of origin, some with post-traumatic stress disorder (PTSD) and now residents in New Zealand, were seen for neuropsychological assessment. Measures were officially translated, back translated, and administered with the assistance of professional interpreters. Multiple challenges arose in terms of administration (e.g., use of interpreters, interactions with the tester, assessment environment, assessment experience, and motivation), scoring, and interpretation (e.g., age appropriate scoring, estimation of prior function, estimation of brain injury severity, obtaining collateral information), the tests themselves, and ecological validity. There are more challenges in the neuropsychological assessment of people who are CALD than can be managed by adhering to current guidelines. The best approach is to find a balance between maintaining assessment integrity and working creatively and sensitively with this group. PMID- 27383251 TI - MEETING NOTICES. PMID- 27383250 TI - Adaptive immunity against gut microbiota enhances apoE-mediated immune regulation and reduces atherosclerosis and western-diet-related inflammation. AB - Common features of immune-metabolic and inflammatory diseases such as metabolic syndrome, diabetes, obesity and cardiovascular diseases are an altered gut microbiota composition and a systemic pro-inflammatory state. We demonstrate that active immunization against the outer membrane protein of bacteria present in the gut enhances local and systemic immune control via apoE-mediated immune modulation. Reduction of western-diet-associated inflammation was obtained for more than eighteen weeks after immunization. Immunized mice had reduced serum cytokine levels, reduced insulin and fasting glucose concentrations; and gene expression in both liver and visceral adipose tissue confirmed a reduced inflammatory steady-state after immunization. Moreover, both gut and atherosclerotic plaques of immunized mice showed reduced inflammatory cells and an increased M2 macrophage fraction. These results suggest that adaptive responses directed against microbes present in our microbiota have systemic beneficial consequences and demonstrate the key role of apoE in this mechanism that could be exploited to treat immune-metabolic diseases. PMID- 27383252 TI - Novel approaches toward managing the micromanagers: 'non-toxic' but effective. PMID- 27383254 TI - Shielding voices: The modulation of binding processes between voice features and response features by task representations. AB - Vocal events offer not only semantic-linguistic content but also information about the identity and the emotional-motivational state of the speaker. Furthermore, most vocal events have implications for our actions and therefore include action-related features. But the relevance and irrelevance of vocal features varies from task to task. The present study investigates binding processes for perceptual and action-related features of spoken words and their modulation by the task representation of the listener. Participants reacted with two response keys to eight different words spoken by a male or a female voice (Experiment 1) or spoken by an angry or neutral male voice (Experiment 2). There were two instruction conditions: half of participants learned eight stimulus response mappings by rote (SR), and half of participants applied a binary task rule (TR). In both experiments, SR instructed participants showed clear evidence for binding processes between voice and response features indicated by an interaction between the irrelevant voice feature and the response. By contrast, as indicated by a three-way interaction with instruction, no such binding was found in the TR instructed group. These results are suggestive of binding and shielding as two adaptive mechanisms that ensure successful communication and action in a dynamic social environment. PMID- 27383253 TI - siRNA targeting the kappa light chain constant region: preclinical testing of an approach to nonfibrillar and fibrillar light chain deposition diseases. AB - Treatment of light chain (LC) deposition diseases both nonfibrillar and fibrillar is aimed at eliminating LC production but success is limited. We report on the testing of an small interfering RNA pool targeting the kappa LC constant region mRNA (si[IGKC]) designed for use against all kappa plasma cell clones. To test for changes in kappa LC message and protein production we used real-time PCR, immunoblot, intracellular mean fluorescence intensity and kappa LC secretion by enzyme-linked immunosorbent assay. In vitro we employed 4 human cell lines that make kappa LCs and 20 specimens of CD138-selected marrow plasma cells from patients with kappa plasma cell diseases. In vivo, we used a murine flank plasmacytoma xenograft model. In vitro and in vivo, there were significant reductions in message and protein production by all modalities in all cell types despite diversity in variable region sequence. In addition, in clones producing intact immunoglobulin, caspase 3/7 activity with si[IGKC] was significantly increased compared with clones producing kappa LC only, consistent with the triggering of a terminal unfolded protein response by excess unpaired heavy chains. In conclusion, si[IGKC] can significantly reduce kappa LC production by kappa plasma cells. Further preclinical development is needed to optimize delivery. PMID- 27383255 TI - Toxicological testing when evaluating fatal cases suspected of acute fentanyl toxicity. PMID- 27383257 TI - Development of the Contact Lens User Experience: CLUE Scales. AB - PURPOSE: The field of optometry has become increasingly interested in patient reported outcomes, reflecting a common trend occurring across the spectrum of healthcare. This article reviews the development of the Contact Lens User Experience: CLUE system designed to assess patient evaluations of contact lenses. CLUE was built using modern psychometric methods such as factor analysis and item response theory. METHODS: The qualitative process through which relevant domains were identified is outlined as well as the process of creating initial item banks. Psychometric analyses were conducted on the initial item banks and refinements were made to the domains and items. Following this data-driven refinement phase, a second round of data was collected to further refine the items and obtain final item response theory item parameters estimates. RESULTS: Extensive qualitative work identified three key areas patients consider important when describing their experience with contact lenses. Based on item content and psychometric dimensionality assessments, the developing CLUE instruments were ultimately focused around four domains: comfort, vision, handling, and packaging. Item response theory parameters were estimated for the CLUE item banks (377 items), and the resulting scales were found to provide precise and reliable assignment of scores detailing users' subjective experiences with contact lenses. CONCLUSIONS: The CLUE family of instruments, as it currently exists, exhibits excellent psychometric properties. PMID- 27383256 TI - Iron overload causes endolysosomal deficits modulated by NAADP-regulated 2-pore channels and RAB7A. AB - Various neurodegenerative disorders are associated with increased brain iron content. Iron is known to cause oxidative stress, which concomitantly promotes cell death. Whereas endolysosomes are known to serve as intracellular iron storage organelles, the consequences of increased iron on endolysosomal functioning, and effects on cell viability upon modulation of endolysosomal iron release remain largely unknown. Here, we show that increasing intracellular iron causes endolysosomal alterations associated with impaired autophagic clearance of intracellular protein aggregates, increased cytosolic oxidative stress and increased cell death. These effects are subject to regulation by NAADP, a potent second messenger reported to target endolysosomal TPCNs (2-pore channels). Consistent with endolysosomal iron storage, cytosolic iron levels are modulated by NAADP, and increased cytosolic iron is detected when overexpressing active, but not inactive TPCNs, indicating that these channels can modulate endolysosomal iron release. Cell death triggered by altered intralysosomal iron handling is abrogated in the presence of an NAADP antagonist or when inhibiting RAB7A activity. Taken together, our results suggest that increased endolysosomal iron causes cell death associated with increased cytosolic oxidative stress as well as autophagic impairments, and these effects are subject to modulation by endolysosomal ion channel activity in a RAB7A-dependent manner. These data highlight alternative therapeutic strategies for neurodegenerative disorders associated with increased intracellular iron load. PMID- 27383260 TI - Advantages of Efficacy and Safety of Fixed-Dose Tafluprost/Timolol Combination Over Fixed-Dose Latanoprost/Timolol Combination. AB - PURPOSE: To compare the safety and efficacy of fixed-dose tafluprost/timolol combination (Taf/T-FDC) with those of fixed-dose latanoprost/timolol combination (Lat/T-FDC) by measuring the intraocular pressure (IOP)-lowering effect, ocular pharmacokinetics, and ocular surface toxicity. METHODS: The IOP-lowering effect of Taf/T-FDC and Lat/T-FDC in ocular normotensive monkeys was evaluated at 4 and 8 h after instillation in study A, at 12, 14, 16, and 18 h after instillation in study B, and at 24, 26, 28, and 30 h after instillation in study C. Drug penetration into the eye was evaluated by measuring the concentrations of timolol, tafluprost acid (active metabolic form of tafluprost), and latanoprost acid (active metabolic form of latanoprost) using liquid chromatography coupled with tandem mass spectrometry after single instillation of Taf/T-FDC or Lat/T-FDC to Sprague Dawley rats. Cytotoxicity following 1-30 min exposure of SV40 transformed human corneal epithelial cells to Taf/T-FDC or Lat/T-FDC was analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) 2H-tetrazolium assays. Undiluted and 10-fold diluted solutions of each FDC were evaluated. RESULTS: The IOP-lowering effect of Taf/T-FDC was almost equivalent to that of Lat/T-FDC at 4-8 h after instillation. The peak IOP reduction of Taf/T FDC and Lat/T-FDC was observed at 8 h after instillation, and there is no difference between the two. The difference between them was observed at 24-30 h after instillation, and Taf/T-FDC demonstrated a significantly greater IOP lowering effect than Lat/T-FDC at 24-30 h after instillation. The IOP-lowering effect of Taf/T-FDC was sustained up to 30 h after instillation, while that of Lat/T-FDC had almost disappeared at 28 h after instillation. Timolol concentrations in aqueous humor after Taf/T-FDC instillation were higher than those after Lat/T-FDC instillation (Cmax, 3870 ng/mL vs 1330 ng/mL; AUCinf, 3970 ng.h/mL vs 1250 ng.h/mL). The concentrations of tafluprost acid and latanoprost acid in aqueous humor after instillation of Taf/T-FDC and Lat/T-FDC, respectively, were similar to those after instillation of mono-preparations of tafluprost and latanoprost, respectively. The cytotoxic effect of Taf/T-FDC to the human corneal epithelial cells was significantly lower than that of Lat/T-FDC at all evaluated time points in both undiluted and 10-fold diluted FDCs. CONCLUSION: Taf/T-FDC provides increased IOP-lowering effect duration and lower potential ocular surface toxicity than Lat/T-FDC. PMID- 27383261 TI - Epithelial-mesenchymal interaction during photodynamic therapy-induced photorejuvenation. AB - Recently, several clinical studies reported that the photodynamic therapy (PDT) has photorejuvenation effects on the aged skin. Previously, our group introduced evidence of direct effect of PDT on cultured fibroblast (FB). PDT directly stimulated FBs and induced collagen synthesis through activation of extracellular signal-regulated kinase. In this study, we investigated indirect effect of PDT on the human dermal FB during photorejuvenation focused on the epithelial mesenchymal interaction between keratinocyte (KC) and FB. The "low-level PDT" condition was used for PDT therapy to the cultured KC. Various kinds of cytokines in the supernatants of KC were evaluated by enzyme-linked immunosorbent assay. FBs were stimulated with the KC-conditioned medium (KCM) taken after PDT. The mRNA level of matrix metalloproteinases (MMPs), transforming growth factor (TGF) beta and collagen type Ialpha in the FB, was determined by real-time polymerase chain reaction. Clinical phtorejuvenation effect was also evaluated from nine patients who had PDT to treat actinic keratoses. Among the FB-stimulating cytokines, a significant elevation of interleukin (IL)-1alpha, IL-6, and tumor necrosis factor-alpha level in KCM was noted after PDT compared with controls. After stimulating FB with KCM, the mRNA of MMP-1 was decreased and the mRNA of collagen type Ialpha was increased compare to control. Clinically, fine wrinkles significantly reduced after PDT. However, coarse wrinkles were not recovered significantly. In conclusion, increased collagen synthesis may be mediated not only by direct effect of PDT on FB but also by indirect effect of PDT on FB through cytokines from KC, such as IL-1alpha, IL-6, and tumor necrosis factor alpha. PMID- 27383262 TI - Chemically Triggered Formation of Two-Dimensional Epitaxial Quantum Dot Superlattices. AB - Two dimensional superlattices of epitaxially connected quantum dots enable size quantization effects to be combined with high charge carrier mobilities, an essential prerequisite for highly performing QD devices based on charge transport. Here, we demonstrate that surface active additives known to restore nanocrystal stoichiometry can trigger the formation of epitaxial superlattices of PbSe and PbS quantum dots. More specifically, we show that both chalcogen-adding (sodium sulfide) and lead oleate displacing (amines) additives induce small area epitaxial superlattices of PbSe quantum dots. In the latter case, the amine basicity is a sensitive handle to tune the superlattice symmetry, with strong and weak bases yielding pseudohexagonal or quasi-square lattices, respectively. Through density functional theory calculations and in situ titrations monitored by nuclear magnetic resonance spectroscopy, we link this observation to the concomitantly different coordination enthalpy and ligand displacement potency of the amine. Next to that, an initial ~10% reduction of the initial ligand density prior to monolayer formation and addition of a mild, lead oleate displacing chemical trigger such as aniline proved key to induce square superlattices with long-range, square micrometer order; an effect that is the more pronounced the larger the quantum dots. Because the approach applies to PbS quantum dots as well, we conclude that it offers a reproducible and rational method for the formation of highly ordered epitaxial quantum dot superlattices. PMID- 27383263 TI - Differentiation of ring-substituted regioisomers of amphetamine and methamphetamine by supercritical fluid chromatography. AB - Chromatographic differentiation of the ring-substituted regioisomers of amphetamine (AMP) and methamphetamine (MA) was performed by supercritical fluid chromatography (SFC). The behaviour of the retention against the changes of column temperature and co-solvent proportion was studied. The obtained information facilitated the optimization of the each regioisomer. As a result, 2 , 3-, and 4-ring-substituted analogues of AMP and MA with methyl, methoxy, fluoro, chloro, and bromo groups were separated, generally within 6 min. In addition, we found that the separation pattern of the examined regioisomers was classified into two, which depended on the electron donating/withdrawing effect of the substituent. Our results indicate that SFC could be used in forensic drug analysis for fast, reliable identification of structurally similar drugs of abuse. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27383264 TI - Energy-resolved technique for discovery and identification of malonyl-triterpene saponins in Caulophyllum robustum by UHPLC-electrospray Fourier transform mass spectrometry. AB - Malonyl-triterpene saponins (MTSs) attract scientific attentions because of their structural diversities and valuable bioactivities. However, its thermal instability brings a huge amount of challenges for isolation and purification of this class of compounds. To our best knowledge, there has been no report on isolation and analysis of MTSs from genus Caulophyllum. In this study, a strategy combining data acquisition using an energy-resolved technique and the narrow widow extracted ion chromatograms as data mining method was developed for discovery and identification of MTSs in Caulophyllum robustum hair roots by ultra high liquid chromatography coupled to electrospray ionization Fourier transform mass spectrometry. The method was performed at an independent MS full scan using our bottom-up energies by in-source collision induced dissociations with 0, 25, 50 and 100 eV in both positive and negative modes. Precursor ion as well as fragment ion information was simultaneously collected from four energy-resolved MS spectra in a single run of 18 min. The fragmentation pathways of intact deprotonated, protonated and sodium ions of MTSs were proposed for the structural elucidation of Caulophyllum MTSs. A flowchart involving a stepwise procedure based on key fragments from ESI- /ESI+ -FT-MS(1, 1) to MS(1, 4) spectra was constructed for the identification of structural elements in the MTSs. As a result, a total of 23 MTSs were discovered and tentatively identified, which had not been reported from Caulophyllum species before. All of these were potentially new compounds. This study provides an excellent example for discovery and identification of MTSs in herb medicines. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27383265 TI - Effect of the environment on the secondary metabolic profile of Tithonia diversifolia: a model for environmental metabolomics of plants. AB - Tithonia diversifolia is an invasive weed commonly found in tropical ecosystems. In this work, we investigate the influence of different abiotic environmental factors on the plant's metabolite profile by multivariate statistical analyses of spectral data deduced by UHPLC-DAD-ESI-HRMS and NMR methods. Different plant part samples of T. diversifolia which included leaves, stems, roots, and inflorescences were collected from two Brazilian states throughout a 24-month period, along with the corresponding monthly environmental data. A metabolomic approach employing concatenated LC-MS and NMR data was utilised for the first time to study the relationships between environment and plant metabolism. A seasonal pattern was observed for the occurrence of metabolites that included sugars, sesquiterpenes lactones and phenolics in the leaf and stem parts, which can be correlated to the amount of rainfall and changes in temperature. The distribution of the metabolites in the inflorescence and root parts were mainly affected by variation of some soil nutrients such as Ca, Mg, P, K and Cu. We highlight the environment-metabolism relationship for T. diversifolia and the combined analytical approach to obtain reliable data that contributed to a holistic understanding of the influence of abiotic environmental factors on the production of metabolites in various plant parts. PMID- 27383266 TI - Metabolomic Approach for Discrimination of Four- and Six-Year-Old Red Ginseng (Panax ginseng) Using UPLC-QToF-MS. AB - Panax ginseng C.A. MEYER is one of the most popular medicinal herbs in Asia and the chemical constituents are changed by processing methods such as steaming or sun drying. Metabolomic analysis was performed to distinguish age discrimination of four- and six-year-old red ginseng using ultra-performance liquid chromatography quadruple time of flight mass spectrometry (UPLC-QToF-MS) with multivariate statistical analysis. Principal component analysis (PCA) showed clear discrimination between extracts of red ginseng of different ages and suggest totally six discrimination markers (two for four-year-old and four for six-year-old red ginseng). Among these, one marker was isolated and the structure determined by NMR spectroscopic analysis was 13-cis-docosenamide (marker 6-1) from six-year-old red ginseng. This is the first report of a metabolomic study regarding the age differentiation of red ginseng using UPLC-QToF-MS and determination of the structure of the marker. These results will contribute to the quality control and standardization as well as provide a scientific basis for pharmacological research on red ginseng. PMID- 27383267 TI - A long-tethered (P-B-P)-pincer ligand: synthesis, complexation, and application to catalytic dehydrogenation of alkanes. AB - A new long-tethered boron-containing (P-B-P)-pincer ligand 8 has been synthesized. Complexation of 8 with [Ir(coe)2Cl]2 (coe = cyclooctene) resulted in (P-B-P)(hydrido)chloroiridium complex (P-B-P)Ir(H)Cl 9. Subsequent reaction with nBuLi led to the formation of dihydride complex (P-B-P)Ir(H)210. Both complexes were found to be moderately active for the catalytic dehydrogenation of alkanes. PMID- 27383268 TI - Cardiac Sympathetic Hyperactivity in Patients with Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea. AB - Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) coexist in 0.5-1% of the general population. Both OSA and COPD are associated with increased sympathetic nervous activity, and patients affected by both disorders have higher risk for increased morbidity and mortality as compared with patients with COPD or OSA alone. We tested the hypothesis that patients with COPD and OSA (Overlap syndrome) have higher sympathetic and lower parasympathetic modulation of heart rate variability (HRV) in comparison with patients suffering from COPD or OSA alone. HRV indices in the frequency domain were evaluated from daytime electrocardiographic recordings in 14 patients with both severe OSA (apnea-hypopnea index >= 30) and mild-to-moderate COPD and compared with those with OSA (n = 24) or COPD (n = 16) alone. We found that, in the Overlap syndrome group, high-frequency (HF, 0.4-0.15 Hz) power was significantly lower (0.18 nu vs 0.34 nu in OSA and 0.44 nu in COPD patients, p < 0.01) and low-frequency (LF, 0.15-0.05 Hz) power was significantly greater (0.82 nu vs 0.66 nu in OSA and 0.57 nu in COPD patients, p < 0.01) compared with COPD and OSA groups. Patients with both OSA and COPD had higher LF/HF ratio as compared with patients in OSA and COPD groups (4.5 [5.9] vs 1.9 [2.6] and 1.3 [1.3], respectively, p < 0.01). For the Overlap syndrome group, there was a significant direct relationship between LF/HF ratio and residual volume (r2 = 0.62, p = 0.007). These findings show that patients with both OSA and COPD have higher sympathetic modulation of heart rate compared with those with OSA or COPD alone. Furthermore, the findings provide a potential mechanism for the increased morbidity and mortality reported in patients suffering from both disorders, suggesting new therapeutic perspectives in Overlap syndrome. PMID- 27383269 TI - Molecular dynamics-based refinement and validation for sub-5 A cryo-electron microscopy maps. AB - Two structure determination methods, based on the molecular dynamics flexible fitting (MDFF) paradigm, are presented that resolve sub-5 A cryo-electron microscopy (EM) maps with either single structures or ensembles of such structures. The methods, denoted cascade MDFF and resolution exchange MDFF, sequentially re-refine a search model against a series of maps of progressively higher resolutions, which ends with the original experimental resolution. Application of sequential re-refinement enables MDFF to achieve a radius of convergence of ~25 A demonstrated with the accurate modeling of beta galactosidase and TRPV1 proteins at 3.2 A and 3.4 A resolution, respectively. The MDFF refinements uniquely offer map-model validation and B-factor determination criteria based on the inherent dynamics of the macromolecules studied, captured by means of local root mean square fluctuations. The MDFF tools described are available to researchers through an easy-to-use and cost-effective cloud computing resource on Amazon Web Services. PMID- 27383270 TI - Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation. AB - Increasing evidence highlights the important roles of microRNAs in mediating p53's tumor suppression functions. Here, we report miR-139-5p as another new p53 microRNA target. p53 induced the transcription of miR-139-5p, which in turn suppressed the protein levels of phosphodiesterase 4D (PDE4D), an oncogenic protein involved in multiple tumor promoting processes. Knockdown of p53 reversed these effects. Also, overexpression of miR-139-5p decreased PDE4D levels and increased cellular cAMP levels, leading to BIM-mediated cell growth arrest. Furthermore, our analysis of human colorectal tumor specimens revealed significant inverse correlation between the expression of miR-139-5p and that of PDE4D. Finally, overexpression of miR-139-5p suppressed the growth of xenograft tumors, accompanied by decrease in PDE4D and increase in BIM. These results demonstrate that p53 inactivates oncogenic PDE4D by inducing the expression of miR-139-5p. PMID- 27383271 TI - Reconstruction of genetically identified neurons imaged by serial-section electron microscopy. AB - Resolving patterns of synaptic connectivity in neural circuits currently requires serial section electron microscopy. However, complete circuit reconstruction is prohibitively slow and may not be necessary for many purposes such as comparing neuronal structure and connectivity among multiple animals. Here, we present an alternative strategy, targeted reconstruction of specific neuronal types. We used viral vectors to deliver peroxidase derivatives, which catalyze production of an electron-dense tracer, to genetically identify neurons, and developed a protocol that enhances the electron-density of the labeled cells while retaining the quality of the ultrastructure. The high contrast of the marked neurons enabled two innovations that speed data acquisition: targeted high-resolution reimaging of regions selected from rapidly-acquired lower resolution reconstruction, and an unsupervised segmentation algorithm. This pipeline reduces imaging and reconstruction times by two orders of magnitude, facilitating directed inquiry of circuit motifs. PMID- 27383272 TI - Neural oscillations as a signature of efficient coding in the presence of synaptic delays. AB - Cortical networks exhibit 'global oscillations', in which neural spike times are entrained to an underlying oscillatory rhythm, but where individual neurons fire irregularly, on only a fraction of cycles. While the network dynamics underlying global oscillations have been well characterised, their function is debated. Here, we show that such global oscillations are a direct consequence of optimal efficient coding in spiking networks with synaptic delays and noise. To avoid firing unnecessary spikes, neurons need to share information about the network state. Ideally, membrane potentials should be strongly correlated and reflect a 'prediction error' while the spikes themselves are uncorrelated and occur rarely. We show that the most efficient representation is when: (i) spike times are entrained to a global Gamma rhythm (implying a consistent representation of the error); but (ii) few neurons fire on each cycle (implying high efficiency), while (iii) excitation and inhibition are tightly balanced. This suggests that cortical networks exhibiting such dynamics are tuned to achieve a maximally efficient population code. PMID- 27383273 TI - Suppression of Phosphatidylinositol 3-Kinase/Akt Signaling Attenuates Hypoxia Induced Pulmonary Hypertension Through the Downregulation of Lysyl Oxidase. AB - Lysyl oxidase (LOX) is a copper-dependent enzyme that catalyzes covalent cross linking of collagen. In response to hypoxia, phosphatidylinositol 3-kinase (PI3K) pathway is activated and contributes to pulmonary arterial hypertension (PAH). However, potential role of LOX in hypoxia-induced PAH is poorly understood. In this study, we explored the mechanism responsible for the development of hypoxia induced PAH. Potent inhibitors of PI3K/Akt and LOX, wortmannin and beta aminopropionitrile (beta-APN), were administrated in rat model of hypoxia-induced PAH. The cross-linking of collagen was assessed by the determination of hydroxyproline. LOX, LOXL-1, LOXL-2, LOXL-3, LOXL-4, Akt, and phospho-Akt expression was detected by real-time polymerase chain reaction and western blot analysis. We observed that collagen cross-linking and LOX activity were elevated in hypoxia-exposed rat lung tissue, but these effects were reversed by beta-APN and wortmannin. In addition, exposure to hypoxia enhanced mRNA and protein expression and activity of LOX and LOXL-1 in a PI3K/Akt-dependent manner and induced the development of PAH. After the administration of wortmannin, the upregulation of LOX and cross-linking of collagen were significantly reversed in hypoxia-exposed rat pulmonary artery tissue. Taken together, the present study demonstrated that the upregulation of LOX expression and collagen cross-linking is PI3K/Akt dependent in rat with hypoxia-induced PAH. Suppression of PI3K/Akt pathway may alleviate hypoxia-induced PAH through the downregulation of LOX. PMID- 27383274 TI - Atlantic Sturgeon Spatial and Temporal Distribution in Minas Passage, Nova Scotia, Canada, a Region of Future Tidal Energy Extraction. AB - In the Bay of Fundy, Atlantic sturgeon from endangered and threatened populations in the USA and Canada migrate through Minas Passage to enter and leave Minas Basin. A total of 132 sub-adult and adult Atlantic sturgeon were tagged in Minas Basin during the summers of 2010-2014 using pressure measuring, uniquely coded, acoustic transmitters with a four or eight year life span. The aim of this study was to examine spatial and seasonal distribution of sturgeon in Minas Passage during 2010-2014 and test the hypothesis that, when present, Atlantic sturgeon were evenly distributed from north to south across Minas Passage. This information is important as tidal energy extraction using in-stream, hydrokinetic turbines is planned for only the northern portion of Minas Passage. Electronic tracking data from a total of 740 sturgeon days over four years demonstrated that Atlantic sturgeon used the southern portion of Minas Passage significantly more than the northern portion. Sturgeon moved through Minas Passage at depths mostly between 15 and 45 m (n = 10,116; mean = 31.47 m; SD = 14.88). Sturgeon mean swimming depth was not significantly related to bottom depth and in deeper regions they swam pelagically. Sturgeon predominately migrated inward through Minas Passage during spring, and outward during late summer-autumn. Sturgeon were not observed in Minas Passage during winter 2012-2013 when monitoring receivers were present. This information will enable the estimation of encounters of Atlantic sturgeon with in-stream hydrokinetic turbines. PMID- 27383275 TI - Airway and head and neck high dependency unit: a single-centre experience. AB - OBJECTIVE: Dedicated otolaryngology high dependency units are uncommon. This paper reports the first experiences of such a facility in the UK, assessing reason for admission, duration of stay, occupancy rate and need for care escalation. The study sought to assess the presence of similar units in the UK. METHODS: A retrospective review of high dependency unit admissions over an 18 month period and a national survey of otolaryngology departments in the UK were conducted to establish the overall presence and location of similar high dependency units. RESULTS: A total of 128 patients were admitted during the study period, mainly following surgery and because of airway compromise. The average duration of stay was 2-3 days (range, 1-12 days). The occupancy rate was 31.7 per cent. No patients required their care to be escalated to the intensive care unit. Seven similar high dependency units were identified in the UK. CONCLUSION: The care provided prevented the need for escalation of care to an intensive care unit. This challenges the need for patient management on intensive care units following major surgery or airway compromise for those not requiring assisted ventilation. High dependency units similar to ours are not widespread. PMID- 27383276 TI - Thiol/disulphide homeostasis in Bell's palsy as a novel pathogenetic marker. AB - OBJECTIVES: The aim of this study was to investigate the relationship between Bell's palsy and a novel oxidative stress parameter, thiol/disulphide homeostasis. DESIGN: A prospective study evaluating oxidative stress in Bell's palsy. SETTING: This research took place in the department of Otorhinolaryngology, Ataturk Training and Research Hospital. PARTICIPANTS: Totally, 77 patients with Bell's palsy and 38 healthy controls were included in this study. MAIN OUTCOME MEASURES: The blood levels of total and native thiol and disulphide activity were assessed, and their levels were compared in the patients and controls. RESULTS: There were statistically significant differences between the patients and controls regarding thiol/disulphide parameters. The mean native thiol and total thiol were significantly lower and disulphide levels were higher in the Bell's palsy than controls. On binary logistic regression analysis, the created model showed 45.3% variation. The cut-off value was 18.95 for disulphides. CONCLUSION: Native and total thiol levels were low in the Bell's palsy. This metabolic disturbance may have a role in the pathogenesis of Bell's palsy. PMID- 27383277 TI - Verteporfin can Reverse the Paclitaxel Resistance Induced by YAP Over-Expression in HCT-8/T Cells without Photoactivation through Inhibiting YAP Expression. AB - BACKGROUND/AIMS: Paclitaxel (PTX) is one of the most effective anti-cancer drugs. However, multiple drug resistance is still the main factor that hinders the effective treatment of cancer with PTX. Several factors including YAP over expression can cause PTX resistance. In this study, we aimed to verify the role YAP plays in PTX resistance, explore the reversal of PTX resistance by verteporfin (VP) and investigate the effect of combination therapy of PTX and VP on the PTX resistant colon cancer cells (HCT-8/T). METHODS: To study the relationship between YAP and PTX resistance, a stable YAP-over-expression or YAP silencing cell line was generated by transfected with YAP-plasmids or siYAP-RNA. WST-1 assay was performed to detect the cytotoxicity of PTX on HCT-8 and HCT-8/T cells. Clone formation assay and Transwell assay was preformed to determine the cell proliferation and invasion ability respectively. Immunofluorescence and Western blot analysis was performed for protein detection. RESULTS: YAP was stronger expressed in HCT-8/T than in HCT-8, and PTX resistance was positively correlated with the level of YAP expression. VP, a strongly YAP inhibitor, could reduce the PTX resistance on HCT-8/T cells without light activation by inhibiting YAP. Beside, VP and PTX combination therapy showed synergism on inhibition of YAP and cytotoxicity to HCT-8/T. Moreover, verteporfin and PTX combination therapy affect the invasion and colony formation ability and induce apoptosis of HCT-8/T cells. CONCLUSIONS: VP can reverse the PTX resistance induced by YAP over expression in HCT-8/T cells without photoactivation through inhibiting YAP expression. PMID- 27383279 TI - A comparison of the variance estimation methods for heteroscedastic nonlinear models. AB - Heteroscedasticity is commonly encountered when fitting nonlinear regression models in practice. We discuss eight different variance estimation methods for nonlinear regression models with heterogeneous response variances, and present a simulation study to compare the performance of the eight methods in terms of estimating the standard errors of the fitted model parameters. The simulation study suggests that when the true variance is a function of the mean model, the power of the mean variance function estimation method and the transform-both sides method are the best choices for estimating the standard errors of the estimated model parameters. In general, the wild bootstrap estimator and two modified versions of the standard sandwich variance estimator are reasonably accurate with relatively small bias, especially when the heterogeneity is nonsystematic across values of the covariate. Furthermore, we note that the two modified sandwich estimators are appealing choices in practice, considering the computational advantage of these two estimation methods relative to the variance function estimation method and the transform-both-sides approach. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27383278 TI - Biosimilar monoclonal antibodies: preclinical and clinical development aspects. AB - Biological drugs and their originated biosimilars are large, highly complex molecules derived from living cells or organisms. Traditional medicines, by contrast, are usually simple molecules of low molecular weight, synthesised by chemical means. The distinct complexities and methods of manufacture create an important difference between biosimilars and conventional generic drugs: while chemical generics can be fully characterised as identical to the originator product, biosimilars cannot. In addition, biological therapies are inherently variable, creating unavoidable differences between even subsequent batches of the same product. An expiring patent does not necessarily mean that the manufacturing process of the originator product becomes available to the biosimilar developers (for instance, the relevant cell line clone and growth medium). Therefore, it cannot be guaranteed that biosimilar products are identical to their reference product on a molecular level. This difference has important implications for the regulation and licensing of biosimilars. While conventional generic drugs require only a limited comparison and demonstration of identical chemical structure to the reference product, biosimilars require far more rigorous testing. In general, there must be a thorough comparison of structural and functional characteristics between biosimilar and originator drug. Stepwise nonclinical in vitro and in vivo approaches are recommended to evaluate the similarity of both drugs and any identified micro-heterogeneities must then be assessed for their impact on safety and clinical performance. Subsequently, clinical pharmacokinetic (PK) studies need to be performed in order to demonstrate a similar PK profile, prior to conducting clinical efficacy trials. PMID- 27383280 TI - Contemporary Neuroradiographic Assessment of the Cochleo-Carotid Partition. AB - PURPOSE: The cochleo-carotid partition (CCP) describes the intimate anatomic relationship between the petrous carotid artery and the cochlear basal turn. This partition bears significant surgical and unique clinical relevance. The purpose of this paper is to radiographically assess the CCP and discuss its clinical implications. METHODS: A total of 155 consecutive fine-cut temporal bone CT scans were retrospectively reviewed, and study scans were digitally analyzed in both axial and coronal views. The shortest distance between the petrous carotid canal and the cochlear basal turn was measured. RESULTS: In all, 310 temporal bones were studied, with a mean CCP of 1.9 mm (range 0.2-8.5, SD 1.1). The following CCP measurements were obtained: <=1.0 mm [n = 46 (14.8%)]; 1.1-2.0 mm [n = 161 (51.9%)]; 2.1-3.0 mm [n = 29 (9.4%)], and >=4.0 mm [n = 12 (4.2%)]. One temporal bone (0.3%) had complete CCP dehiscence. There was a positive correlation between each patient's right and left CCP measures (p < 0.005) and a significant negative correlation between CCP grade and age (p = 0.027). CONCLUSIONS: The CCP is a narrow anatomic confinement measuring <=2 mm in 66.7% of patients. Potential implications of the CCP include iatrogenic risks, its possible function as a third inner ear window in patients with audiovestibular symptoms, and pathophysiology of new-onset tinnitus following cochlear implantation. PMID- 27383281 TI - Medicolegal-Malpractice and Ethical Issues in Radiology. PMID- 27383282 TI - Increasing dietary fruits and vegetables to reduce healthcare costs. PMID- 27383283 TI - Are HDL receptors really located where we think they are in the liver? PMID- 27383284 TI - Exploring cellular cholesterol-focused strategies in the treatment of cardiometabolic diseases. PMID- 27383285 TI - Ins and outs of the ATP-binding cassette transporter A1. PMID- 27383286 TI - Editorial introduction. PMID- 27383287 TI - The ecology, distribution, conservation and management of large old trees. AB - Large old trees are some of the most iconic biota on earth and are integral parts of many terrestrial ecosystems including those in tropical, temperate and boreal forests, deserts, savannas, agro-ecological areas, and urban environments. In this review, we provide new insights into the ecology, function, evolution and management of large old trees through broad cross-disciplinary perspectives from literatures in plant physiology, growth and development, evolution, habitat value for fauna and flora, and conservation management. Our review reveals that the diameter, height and longevity of large old trees varies greatly on an inter specific basis, thereby creating serious challenges in defining large old trees and demanding an ecosystem- and species-specific definition that will only rarely be readily transferable to other species or ecosystems. Such variation is also manifested by marked inter-specific differences in the key attributes of large old trees (beyond diameter and height) such as the extent of buttressing, canopy architecture, the extent of bark micro-environments and the prevalence of cavities. We found that large old trees play an extraordinary range of critical ecological roles including in hydrological regimes, nutrient cycles and numerous ecosystem processes. Large old trees strongly influence the spatial and temporal distribution and abundance of individuals of the same species and populations of numerous other plant and animal species. We suggest many key characteristics of large old trees such as extreme height, prolonged lifespans, and the presence of cavities - which confer competitive and evolutionary advantages in undisturbed environments - can render such trees highly susceptible to a range of human influences. Large old trees are vulnerable to threats ranging from droughts, fire, pests and pathogens, to logging, land clearing, landscape fragmentation and climate change. Tackling such diverse threats is challenging because they often interact and manifest in different ways in different ecosystems, demanding targeted species- or ecosystem-specific responses. We argue that novel management actions will often be required to protect existing large old trees and ensure the recruitment of new cohorts of such trees. For example, fine-scale tree-level conservation such as buffering individual stems will be required in many environments such as in agricultural areas and urban environments. Landscape level approaches like protecting places where large old trees are most likely to occur will be needed. However, this brings challenges associated with likely changes in tree distributions associated with climate change, because long-lived trees may presently exist in places unsuitable for the development of new cohorts of the same species. Appropriate future environmental domains for a species could exist in new locations where it has never previously occurred. The future distribution and persistence of large old trees may require controversial responses including assisted migration via seed or seedling establishment in new locales. However, the effectiveness of such approaches may be limited where key ecological features of large old trees (such as cavity presence) depend on other species such as termites, fungi and bacteria. Unless other species with similar ecological roles are present to fulfil these functions, these taxa might need to be moved concurrently with the target tree species. PMID- 27383288 TI - How to differentiate renal senescence from chronic kidney disease in clinical practice. AB - Renal aging is frequently confused with chronic nephropathy in clinical practice, since there are some similarities between them, particularly regarding reduced glomerular filtration rate (GFR). However, there are many differences between these two entities which can help any practitioner to distinguish between them, such as: GFR deterioration rate, hematocrit, renal handling of urea, creatinine and some electrolytes, tubular acidification, urinalysis, and renal imaging. Differentiation between renal aging and chronic renal disease is crucial in order to avoid unnecessary medicalization of what is a physiological change associated with the healthy aging process, and the potential harmful consequences of such overdiagnosis. A recently described equation (HUGE), as well as an adequate nephrological evaluation and follow up can help physicians to distinguish both entities. PMID- 27383289 TI - Ameliorative effects of alpha-lipoic acid on high-fat diet-induced oxidative stress and glucose uptake impairment of T cells. AB - The incidence of obesity and metabolic disease continues to rise, mainly associated with consumption of a high-fat diet (HFD). Previous studies have indicated that HFD could disturb the immune system, leading to immunodeficiency and inflammation. Several mechanisms have been postulated to account for immunodeficiency associated with HFD, one being oxidative stress. To further investigate the effects of HFD on glucose metabolism and proliferative capability of T cells and the protective effects of alpha-lipoic acid (LA), male C57BL/6J mice were fed a normal chow (10% fat), an HFD (60% fat), an LA supplement (HFD +0.1%LA), and a N-acetyl-L-cysteine supplement (HFD +0.1% NAC) for 10 weeks. Results showed that 10-week HFD increased intracellular reactive oxygen species (ROS) production, induced oxidative stress state formation, inhibited glucose uptake, decreased ATP concentration, reduced proliferative rate, and dampened IL 2 production of T cells of mice. Administration of LA significantly alleviated these changes induced by HFD. These findings reveal that oxidative stress of T cells caused by HFD may be a key factor leading to glucose metabolism reduction and proliferative capability and function impairment of T cells. LA, as a potent agonist, could promote Nrf2 nuclear translocation and up-regulate expression of Nrf2 target genes (Ho-1 and Prdx1), which can eliminate excess ROS and restore redox balance of cells. PMID- 27383290 TI - L1 arrest, daf-16/FoxO and nonautonomous control of post-embryonic development. AB - Post-embryonic development is governed by nutrient availability. L1 arrest, dauer formation and aging illustrate how starvation, anticipation of starvation and caloric restriction have profound influence on C. elegans development, respectively. Insulin-like signaling through the Forkhead box O transcription factor daf-16/FoxO regulates each of these processes. We recently reported that ins-4, ins-6 and daf-28 promote L1 development from the intestine and chemosensory neurons, similar to their role in dauer development. daf-16 functions cell-nonautonomously in regulation of L1 arrest, dauer development and aging. Discrepancies in daf-16 sites of action have been reported in each context, but the consensus implicates epidermis, intestine and nervous system. We suggest technical limitations of the experimental approach responsible for discrepant results. Steroid hormone signaling through daf-12/NHR is known to function downstream of daf-16 in control of dauer development, but signaling pathways mediating cell-nonautonomous effects of daf-16 in aging and L1 arrest had not been identified. We recently showed that daf-16 promotes L1 arrest by inhibiting daf-12/NHR and dbl-1/TGF-beta Sma/Mab signaling, two pathways that promote L1 development in fed larvae. We will review these results on L1 arrest and speculate on why there are so many signals and signaling centers regulating post-embryonic development. PMID- 27383292 TI - Self-assembly of pseudo-rotaxane and rotaxane complexes using an electrostatic slippage approach. AB - The protonation of a cyclic tertiary amine, integrated into the structure of a dumbbell-shaped guest molecule, accelerates the sliding of the guest through the cavity of a crown ether macrocycle to yield a stable pseudo-rotaxane complex. The use of an amine with the appropriate ring size followed by a proton transfer reaction leads to the formation of an interlocked rotaxane species. PMID- 27383291 TI - Trifluoroselenomethionine: A New Unnatural Amino Acid. AB - Trifluoroselenomethionine (TFSeM), a new unnatural amino acid, was synthesized in seven steps from N-(tert-butoxycarbonyl)-l-aspartic acid tert-butyl ester. TFSeM shows enhanced methioninase-induced cytotoxicity, relative to selenomethionine (SeM), toward HCT-116 cells derived from human colon cancer. Mechanistic explanations for this enhanced activity are computationally and experimentally examined. Comparison of TFSeM and SeM by selenium EXAFS and DFT calculations showed them to be spectroscopically and structurally very similar. Nonetheless, when two different variants of the protein GB1 were expressed in an Escherichia coli methionine auxotroph cell line in the presence of TFSeM and methionine (Met) in a 9:1 molar ratio, it was found that, surprisingly, 85 % of the proteins contained SeM residues, even though no SeM had been added, thus implying loss of the trifluoromethyl group from TFSeM. The transformation of TFSeM into SeM is enzymatically catalyzed by E. coli extracts, but TFSeM is not a substrate of E. coli methionine adenosyltransferase. PMID- 27383293 TI - Lower-dose intravenous immunoglobulins for the treatment of fetal and neonatal alloimmune thrombocytopenia: a cohort study. AB - BACKGROUND: Intravenous immunoglobulins (IVIGs) are the cornerstone in the treatment of pregnancies at risk for fetal and neonatal alloimmune thrombocytopenia (FNAIT). The most commonly used dose is 1.0 g/kg/week, not based on any dose-finding study. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to describe the amount of severe thrombocytopenia according to two different doses of IVIG. STUDY DESIGN AND METHODS: We performed a cohort study, where two dosage regimes of IVIG were evaluated in the treatment of pregnant women suffering from FNAIT with a previous affected child without intracranial hemorrhage (ICH). Cases, treated with 0.5 or 1.0 g/kg/week, were selected from the international multicenter No IntraCranial Hemorrhage (NOICH) registry. Outcome was neonatal platelet (PLT) count at birth and amount of severe thrombocytopenia. Furthermore the appearance of ICH was analyzed. RESULTS: A total of 109 women were included in the study, 46 in the 0.5 IVIG group and 63 in the 1.0 IVIG group. There was no difference in PLT count at birth (mean, 112 vs. 119; crude difference, 7; confidence interval [CI], -37.4 to 23.7]) and incidence of severe thrombocytopenia (<30 * 10(9) /L; n = 7/46 vs. n = 7/63; odds ratio, 1.43 [CI, 0.46-4.42]). No ICH occurred. CONCLUSION: In pregnancies with FNAIT with a previous affected child without ICH, treatment with IVIG in a weekly dose of 0.5 or 1.0 g/kg results in comparable neonatal PLT count at birth and degree of thrombocytopenia. PMID- 27383294 TI - The importance of visceral adipose tissue as a scale for assessing the metabolic syndrome and obesity. PMID- 27383295 TI - Salivary bacterial leakage into implant-abutment connections: preliminary results of an in vitro study. AB - OBJECTIVE: The occurrence of bacterial leakage in the internal surface of implants, through implant-abutment interface (IAI), is one of the parameters for analyzing the fabrication quality of the connections. The aim of this in vitro study is to evaluate two different types of implant-abutment connections: the screwed connection (Group 1) and the cemented connection (Group 2), analyzing the permeability of the IAI to bacterial colonization, using human saliva as culture medium. PATIENTS AND METHODS: A total of twelve implants were tested, six in each experimental group. Five healthy patients were enrolled in this study. Two milliliters of non-stimulated saliva were collected from each subject and mixed in a test tube. After 14 days of incubation of the bacteria sample in the implant fixtures, a PCR-Real Time analysis was performed. Fisher's exact test was used to compare the proportions of implant-abutment assembled structures detected with bacterial leakage. Differences in the bacterial counts of the two groups were compared using the Mann-Whitney U test. A p value < 0.05 was considered significant. RESULTS: The results showed a decreased stability with the screwed implant-abutment connections compared to the cemented implant-abutment connections. A mean total bacterial count of 1.2E+07 (+/- 0.25E+07) for Group 1 and of 7.2E+04 (+/- 14.4E+04) for Group 2 was found, with a high level of significance, p = .0001. CONCLUSIONS: Within the limitations of this study it can be concluded that bacterial species from human saliva may penetrate along the implant-abutment interface in both connections, however the cemented connection implants showed the lowest amount of bacterial colonization. PMID- 27383296 TI - Epiregulin-loaded PLGA nanoparticles increase human keratinocytes proliferation: preliminary data. AB - OBJECTIVE: Epiregulin is a member of the epidermal growth factor (EGF) family produced by keratinocytes: the aim of this study was to investigate the ability of biocompatible nanoparticles loaded with such growth factor to increase human keratinocytes proliferation. MATERIALS AND METHODS: Different PLGA (Poly-d,l lactide-co-glycolide)-nanoparticles (NPs) formulations have been characterized in size and zeta potential by dynamic light scattering (DLS) analysis. The ability of the different PLGA-NPs formulations to adhere onto dental surfaces has been tested, and epiregulin-enriched PLGA-NPs has been produced. Epiregulin release from NPs has been tested by enzyme-linked immunosorbent (ELISA) assay and the proliferative effects of epiregulin-NPs on human keratinocytes have been evaluated. RESULTS: DLS analysis revealed a different size distribution depending on the PLA/PGA (poly lactic acid/poly glycolic acid) ratio used. 50:50 PLGA-NPs exhibited the smaller size and the best dental adhesive ability. Moreover, such epiregulin-loaded NPs was able to increase cell proliferation. CONCLUSIONS: Direct dental pocket drug delivery implies the NPs solution loading onto the dental surface at the cement-enamel junction level: 50:50 PLGA-NPs, with their small size and excellent adhesive ability, represent an interesting tool to deliver epiregulin directly where there is the need for epithelial proliferation. These results describe a possible strategy for periodontal pocket delivery of Epiregulin-loaded PLGA-NPs and might provide a new approach for the treatment of gingival recession, where gingival epithelium proliferation is needed. PMID- 27383297 TI - Is vaginal fractional CO2 laser treatment effective in improving overactive bladder symptoms in post-menopausal patients? Preliminary results. AB - OBJECTIVE: To evaluate the role of vaginal fractional CO2 laser treatment in the relief of Overactive Bladder (OAB) symptoms in post-menopausal women. PATIENTS AND METHODS: Post-menopausal women who complained of one or more symptoms related to vulvo-vaginal atrophy (VVA), who experienced symptoms of OAB and who underwent vaginal treatment with fractional CO2 laser were enrolled in the study. At baseline (T0) and 30 days post-treatment T1), vaginal status (using Vaginal Health Index - VHI), subjective intensity of VVA symptoms (using a visual analog scale - VAS) and micturition diary were evaluated. OAB symptoms were also assessed using a validated questionnaire. RESULTS: Thirty patients were enrolled. A statistically significant improvement in VVA symptoms was observed and in VHI at T1 (p < 0.0001). A significant improvement was also identified in the micturition diary, in number of urge episodes and OAB-q (p < 0.0001). Nine of the 30 patients suffered from incontinence episodes and had improved at T1. CONCLUSIONS: We showed that fractionated CO2 laser vaginal treatment has proved to be effective in improving OAB symptoms in post-menopausal women. Moreover, it is a safe and efficacious measure for the relief of VVA related conditions. Further long-term studies are needed to confirm these preliminary results. PMID- 27383298 TI - Fibula extension and correction of foot and ankle deformity to rectify post osteomyelitis talipes equinovarus in a young adult: a case report and literature review. AB - OBJECTIVE: Talipes equinovarus is traditionally viewed in the literature as a congenital disease. CASE REPORT: We present here a case of the acquired talipes equinovarus (clubfoot) in a young adult patient that has developed the following osteomyelitis. RESULTS: We have successfully corrected this condition by fibula extension and correction of foot and ankle deformity, using external fixation device. The treatment period has extended over three years and involved two operations. CONCLUSIONS: This case report will increase awareness of adult orthopedists on acquired talipes equinovarus and propose orthopedic reconstructive strategies to rectify this condition. PMID- 27383299 TI - The use of damage control orthopaedics to minimize negative sequelae of surgery delay in elderly comorbid patients with hip fracture. AB - Hip surgeries count to the most frequent orthopaedic operations in older patients. Nonelective surgeries for hip fractures cause substantial economic burden because of high costs of medical treatment and high associated mortality. Surgery for hip fracture in the elderly comorbid patient still presents a challenge to orthopaedic surgeons. It is recommended that this surgery is performed within 48 hours after sustaining the hip fracture to decrease mortality. Yet the recommended early surgery (i.e. 48 hours after the incident) is not always feasible due to the frequent overall frailty of the patients or conditions of concomitant disease. The care of patients unfit for early surgery has been not adequately addressed in the literature. We have previously introduced an algorithm based on ASA-PS and P-POSSUM scores to stratify elderly comorbid patients for early vs delayed hip surgery, and used principles of Damage Control Orthopaedics to minimized negative sequelae of surgery delay (Dong C et al., PLoS One 2016). In this paper, we elaborate on Damage Control Orthopaedics and the proposed approach in the context of frequent comorbidities in the elderly orthopaedic patients. Further studies on this subject are urgently needed to establish international consensus on hip fracture surgery delayed due to overall patient frailty or extensive comorbidities. PMID- 27383300 TI - An update on clinical applications of hepatospecific contrast media in magnetic resonance imaging of liver parenchyma. AB - Hepatobiliary-specific contrast agents are now widely used in magnetic resonance imaging (MRI) of liver parenchyma. As extracellular fluid agents, they provide informations regarding lesion vascularity and their use in the hepatobiliary or delayed phase (DPI), and give additional data regarding hepatocyte presence and function. The aim of this article is to review the recent literature about MRI using hepatobiliary-specific contrast agents and to discuss benefits and limits of their clinical applications. Since November 2008, hepatobiliary contrast agents were routinely employed in our Institution for the characterization of equivocal liver lesions detected by other imaging modalities, and for the evaluation of hepatic nodules in liver cirrhosis. The informations provided are particularly relevant for the detection of metastases, for the differentiation between focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA), and for the detection and differentiation between dysplastic nodules (DNs) and hepatocellular carcinoma (HCC) in the cirrhotic liver. The role in the cirrhosis grading and the quantification of liver function is still controversial. Finally, their biliary excretion allows evaluation of anatomy and function of the biliary tree. According to our and reported data, hepatobiliary contrast agents are able to improve liver lesions detection and characterization; their introduction in clinical practice has improved MRI diagnostic efficacy/accuracy, allowing to decrease the number of invasive diagnostic procedures. PMID- 27383301 TI - Evidence for miR-17-92 and miR-134 gene cluster regulation of ovarian cancer drug resistance. AB - OBJECTIVE: Ovarian cancer treatments are often impeded by drug resistance. It has been proposed that microRNA (miRNA) expression patterns may play a role in drug resistance among ovarian cancers. The present study investigated the relationship between resistance to the cancer drug paclitaxel and miRNA expression. MATERIALS AND METHODS: We compared the expression patterns of miRNA genes in paclitaxel sensitive (SKOV3) and paclitaxel-resistant (SKOV3-TR30) cell lines. RESULTS: Expression of the miR-134 gene cluster was found to be significantly lower in the paclitaxel-resistant cell line than in the paclitaxel-sensitive cell line, while the expression of the miR-17-92 gene cluster was significantly higher in the paclitaxel-resistant cells. An analysis of miRNA target gene protein expression revealed that several targets of miR-17-92 were significantly altered between the two cell types. CONCLUSIONS: The higher expression of miR-17-92 and lower expression of mi-134 and the associated alterations of target gene expression may be associated with the drug-resistant nature of some ovarian cancers. PMID- 27383302 TI - Investigating key genes associated with ovarian cancer by integrating affinity propagation clustering and mutual information network analysis. AB - OBJECTIVE: The objective of the present work was to investigate key genes in ovarian cancer based on mAP-KL method which comprised the maxT multiple hypothesis (m), Krzanowski and Lai (KL) cluster quality index, and affinity propagation (AP) clustering algorithm, and mutual information network (MIN) constructed by the context likelihood of relatedness (CLR) algorithm. MATERIALS AND METHODS: MAP-KL method was employed to identify exemplars in ovarian cancer, of which the maxT function ranked the genes of train set and test set and obtained top 200 genes; KL cluster index was utilized to determine the quantity of clusters; and then AP clustering algorithm was conducted to identify the clusters and their exemplars. Also, we assessed the classification performance of mAP-KL by support vector machines (SVM) model. Subsequently, the MIN for exemplars and cluster genes was constructed according to CLR algorithm. Finally, topological centrality properties of exemplars in MIN were assessed to investigate key genes for ovarian cancer. RESULTS: SVM model validated that the classification between normal controls and ovarian cancer patients by mAP-KL had a good performance. A total of 22 clusters and exemplars were detected by performing the mAP-KL method. Based on the topological centrality analyses for exemplars in MIN, we considered the C9orf16, COX5B and ACTB to be key genes in the progress of ovarian cancer. CONCLUSIONS: We have obtained three key genes (C9orf16, COX5B and ACTB) for ovarian cancer on the basis of mAP-KL method and MIN analysis. These genes might be potential biomarkers for treatment of ovarian cancer, and give insight for revealing the underlying mechanism of this tumor. PMID- 27383303 TI - MicroRNA-216b is downregulated in hepatocellular carcinoma and inhibits HepG2 cell growth by targeting Forkhead box protein M1. AB - OBJECTIVE: Aberrantly expressed microRNAs (miRs) may play critical roles in the regulation of tumorigenicity of various cancers. The present study was designed to investigate the expression, function and the underlying mechanism of miR-216b in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The expression of miR 216b and FOXM1 in 24 paired HCC tissues and adjacent normal tissues was determined by Real-time PCR. The proliferative activity of HepG2 cells was determined by MTT assay. We analyzed cell cycle progression by flow cytometry, apoptosis by cell death enzyme-linked immunosorbent assay (ELISA) and cleaved caspase-3 by western blot. Luciferase reporter assay was employed to verify whether FOXM1 serves as a target of miR-216b in vitro. RESULTS: The expression of miR-216b was significantly decreased in HCC tissues compared with that in adjacent normal tissues, whereas FOXM1 expression was increased. In addition, FOXM1 and miR-216b expression were inversely correlated in HCC tissues. Ectopic expression of miR-216b produced a suppressive effect on the growth of HepG2 cells and induced cell cycle arrest and apoptosis. We further demonstrated that miR 216b targets the 3' untranslated region (UTR) of FOXM1 directly to suppress the expression of FOXM1, and that suppression of FOXM1 produced the similar effects to miR-216b CONCLUSIONS: These data suggest that down-regulation of miR-216b directly contributes to the up-regulation of FOXM1, which may confer the tumorigenicity of HCC cells. MiR-216b may serve as a potential therapeutic agent for HCC. PMID- 27383304 TI - FBXL5 attenuates RhoGDI2-induced cisplatin resistance in gastric cancer cells. AB - OBJECTIVE: The hemerythrin-like domain of F-box and leucine-rich repeat protein 5 (FBXL5), an E3 ubiquitin ligase subunit, has critical roles in the regulation of cancer cells metastasis and chemoresistance by targeting diverse substrates for ubiquitin-mediated destruction. MATERIALS AND METHODS: Here, we report that FBXL5 interacts with Rho GDP dissociation inhibitor 2 (RhoGDI2) and attenuates RhoGDI2 induced cisplatin resistance in gastric cancer cells. By utilizing immunoprecipitation (IP) coupled with mass spectrometry assay, we found that FBXL5 regulated gastric cancers migration via cortactin destruction. RESULTS: Depletion of FBXL5 enhances cisplatin resistance of gastric cancer cells through Erk and p38 activation. However, FBXL5 did not affect the abundance and stability of RhoGDI2. Instead, FBXL5 was rapidly degraded in response to cisplatin treatment in RhoGDI2-overexpressing gastric cancer cells. CONCLUSIONS: Collectively, our data suggested the existence of a FBXL5-RhoGDI2 negative feedback loop in RhoGDI2-induced cisplatin resistance in gastric cancer cells, implicating FBXL5 as a novel and promising therapeutic target for RhoGDI2-induced cisplatin resistance gastric cancers. PMID- 27383305 TI - Circulating DNA for detection of gastric cancer. AB - OBJECTIVE: Gastric cancer (GC) is one of the most common malignant tumors worldwide, particularly, prevalent in China. Despite the decreasing incidence of GC in China, the 5-year survival rate is still not over 30% yet. Therefore, early diagnosis and therapeutic outcome evaluation of GC remains as the issue to be resolved in a clinical setting. MATERIALS AND METHODS: Recent studies have found the presence of a certain amount of circulating DNA in the peripheral blood of patients with malignant tumor and shown that these free DNA bear tumor-specific genetic information. The circulating DNA detection includes quantitative and qualitative methods and analysis. Combined monitoring of changes in circulating DNA levels and aberrant alteration of relevant tumor genes is likely to provide comprehensive real-time information to patients. RESULTS: Under normal conditions, oncogene presents in the form of proto-oncogene such as K-ras, which is in non-carcinogenic status under the influence of tumor suppressor gene. When tumor suppressor gene is damaged or mutated of oncogene itself is induced for instance P53, oncogene is then activated and induces tumorigenesis. However, compared to gene mutation detection, the detection of DNA methylation is relatively more well-developed and stable. CONCLUSIONS: This article reviews the current status of the research on circulating DNA in the diagnosis, assessment of response to therapy and prognostic evaluation in GC. In addition, the advantage, current issue and prospect of using circulating DNA as tumor marker are also analyzed. PMID- 27383306 TI - Inhibition of miR-141 reverses cisplatin resistance in non-small cell lung cancer cells via upregulation of programmed cell death protein 4. AB - OBJECTIVE: MicroRNAs are a class of essential regulators in cancer, and previous studies have shown that miR-141 is a tumor suppressor in non-small cell lung cancer (NSCLC). However, it is still unknown whether it regulates chemosensitivity. We aimed to investigate the role of miR-141 in cisplatin resistance in NSCLC cells. MATERIALS AND METHODS: MiR-141 expression in A549 and A549/DDP cell lines have been quantified by real-time PCR. Protein level of PDCD4 and caspase-3 have been determined by Western blot analysis. Drug sensitivity and apoptosis have been determined by MTT assay and TUNEL assay, respectively. Luciferase activity assay was employed to validate the relationship between 3'UTR of PDCD4 mRNA and miR-141. RESULTS: We observed that miR-141 expression was significantly up-regulated in cisplatin-resistant A549/DDP cells compared with the parental cell line A549; and PDCD4, an important apoptosis regulator, was found to be down-regulated. Luciferase activity assay and Western blot analysis confirmed that PDCD4 is a direct target of miR-141. Inhibition of miR-141 in A549/DDP cells markedly increased cisplatin sensitivity and apoptosis, which was partially abrogated by PDCD4 inhibition, indicating that PDCD4 is a functional target of miR-141 in of the regulation of cisplatin sensitivity. CONCLUSIONS: Our data showed that miR-141 participates in regulating cisplatin sensitivity in non small lung cancer cells via PDCD4 inhibition, and suppression of miR-141 might be a therapeutic method to overcome cisplatin resistance in clinical practice. PMID- 27383307 TI - Tramadol regulates proliferation, migration and invasion via PTEN/PI3K/AKT signaling in lung adenocarcinoma cells. AB - OBJECTIVE: Tramadol is used mainly for the treatment of moderate to severe chronic cancer pain. However, the effect of tramadol on lung cancer remains unclear. Therefore, it is important to explore the mechanism accounting for the function of tramadol on lung cancer. MATERIALS AND METHODS: We investigated the effects of tramadol on the proliferation, migration and invasion in human lung adenocarcinoma cells in vitro by CCK-8 assay, wound healing assay and Transwell assay, respectively. We also explored the potential mechanism of tramadol on lung cancer cells by Western blotting. RESULTS: A549 and PC-9 cells were incubated with 2 uM tramadol for different time (0, 7, 14 and 28 d). The in vitro experiments showed that tramadol treatment significantly inhibited cell proliferation, migration and invasion in a time-dependent manner. Moreover, administration of tramadol suppressed tumor growth in vivo. The data also revealed that tramadol could up-regulate the protein expression level of PTEN and consistently inhibit the phosphorylation level of PI3K and Akt, whereas the total level of PI3K and Akt remain unchanged. CONCLUSIONS: These findings indicated that tramadol inhibited proliferation, migration and invasion of human lung adenocarcinoma cells through elevation of PTEN and inactivation of PI3K/Akt signaling. PMID- 27383308 TI - Targeting TGF-beta1 and AKT signal on growth and metastasis of anaplastic thyroid cancer cell in vivo. AB - OBJECTIVE: We have recently reported that therapies targeting TGF-beta1 signaling were effective to prevent the anaplastic thyroid cancer (ATC) cell growth, but not the invasion. Phosphatidylinositol 3-kinase (PI3K)/AKT signaling are activated in ATC and play a major role in ATC invasion. Herein, we examined the effects of targeting TGF-beta1 by shRNA in combination with pan-AKT inhibitor, MK 2206 on growth and metastasis of ATC xenografts implanted in severe combined immunodeficient mice. MATERIALS AND METHODS: 8505C cells or 8505C/shRNA cells or 8505C/TGF-beta1 shRNA cells were implanted sc in 5-week-old female nude mice. Upon establishment of palpable tumours, MK-2206 was administered at 60 mg/kg, orally, three times a week for 6 weeks. RESULTS: The results showed that TGF beta1/shRNA alone only prevents anaplastic thyroid cancer (ATC) tumor formation, but not lung metastasis. MK-2206 alone only inhibits lung metastasis, but not tumor formation. The combined treatment with TGF-beta1/shRNA and MK-2206 led to an approximately 71% growth inhibition compared with TGF-beta1/shRNA (44%) and MK 2206 (15%). The combined treatment with TGF-beta1/shRNA and MK-2206 significantly inhibits lung metastasis. CONCLUSIONS: These findings demonstrated that targeting TGF-beta1 in combination with MK-2206 was the effective method for treatment of ATC. PMID- 27383309 TI - Long non-coding RNA CRNDE promotes tumor growth in medulloblastoma. AB - OBJECTIVE: Medulloblastoma is the most common malignant brain tumor in children. Despite remarkable advances over the past decades, a novel therapeutic strategy is urgently required to increase long-term survival. This study aimed to understand the role of a long non-coding RNA (lncRNA), colorectal neoplasia differentially expressed (CRNDE), in medulloblastoma tumor growth. MATERIALS AND METHODS: The transcript level of CRNDE was initially examined in dissected clinical tissues and cultured cancerous cells. Effects of CRNDE knockdown on cell viability and colony formation in vitro were assessed using the CCK-8 and colony formation assays, respectively. Cell cycle progression and survival were also determined after CRNDE knockdown. A xenograft mouse model of human medulloblastoma was established by injecting nude mice with medulloblastoma cells stably depleted of CRNDE expression. RESULTS: Our data suggest that transcript levels of CRNDE are elevated in clinical medulloblastoma tissues instead of in adjacent non-cancerous tissues. Knockdown of CRNDE significantly slowed cell proliferation rates and inhibited colony formation in Daoy and D341 cells. Tumor growth in vivo was also inhibited after CRNDE knockdown. Moreover, after knockdown of CRNDE, cell cycle progression was arrested in S phase and apoptosis was promoted by 15-20% in Daoy and D341 cells. In vivo data further showed that proliferating cell nuclei antigen (PCNA) was decreased, whereas the apoptosis initiator cleaved-caspase-3 was increased upon CRNDE knockdown in cancerous tissues from the mouse model. CONCLUSIONS: All these data suggest that CRNDE promotes tumor growth both in vitro and in vivo. This growth-promotion effect might be achieved via arresting cell cycle progression and inhibiting apoptosis. Therapeutics against CRNDE may be a novel strategy for the treatment of medulloblastoma. PMID- 27383310 TI - Intermediate filament Nestin and the cell motility in cancer - a review. Retracted AB - The intermediate filaments (Ifs) constitute the cytoskeleton which is a key feature of both prokaryotic and eukaryotic cells. The IFs are expressed throughout life and are involved in the regulation of cell differentiation, homeostasis, ageing and pathogenesis. The IFs not only provide structural integrity to the cell, but they are involved also in a range of cellular functions from organelle trafficking and cell migration to signaling transduction. The IFs are highly dynamic proteins, able to respond and adapt their network rapidly in response to intra- and extra-cellular cues. In cancer, these IFs play a crucial role with regard to cell invasion vial cell motility. The present review article will enlighten information about important IF nestin with regard to its role in cancer cell motility and invasion. PMID- 27383311 TI - Vimentin and post-translational modifications in cell motility during cancer - a review. AB - The post-translational modifications (PTMs) are defined as the covalent modification or enzymatic modification of proteins during or after protein biosynthesis. Proteins are synthesized by ribosomes translating mRNA into polypeptide chains, which may then undergo PTM to form the mature protein product. PTMs are important components in cell signaling. Moreover, it is a known fact that PTM regulation offers an immense array and depth of regulatory possibilities. The present review article will focus on their possible role in cancer cell motility with special reference to vimentin, an intermediate filament (IF), as the later is an important process responsible for life-threatening state viz. cancer metastasis. PMID- 27383312 TI - Does diazinon-sprayed market melon alter cholinesterase activity in healthy consumers? A randomized control trial. AB - OBJECTIVE: Food contributes in measurable body burden of the widely used organophosphate pesticides. We designed a randomized controlled open label trial in Mashhad University Hospital in Iran, to study the possible alterations in cholinesterase activity resulting from consuming market melon known to be exposed to diazinon. PATIENTS AND METHODS: Fifty-three young healthy volunteers were recruited. Participants were randomized to consume 250 g per day of organic (N = 22) vs. market melon (N = 31) during fifteen days. The primary outcome was the variation of red blood-cell (RBC) cholinesterase activity between day 15 (after) and day 0 (prior the intervention). The secondary outcome was a variation of the plasma cholinesterase activity between both dates. RESULTS: Baseline RBC [5.21 +/ 0.93 vs. 5.53 +/- 0.99 IU/mL, mean +/- SD] and plasma cholinesterase activities [54.0 +/- 8.1 vs. 57.4 +/- 8.6%] did not significantly differ between organic and market melon-exposed participants, respectively. RBC [5.86 +/- 1.27 vs. 5.11 +/- 1.2 IU/mL] and plasma cholinesterase activities [58.7 +/- 10.0 vs. 50.5 +/- 13.0%] significantly increased in organic melon-exposed vs. market melon-exposed participants (p = 0.002 and p = 0.001, respectively). CONCLUSIONS: RBC and plasma cholinesterase activities significantly improved after eating organic instead of market melon during fifteen days. However, the consequences on the health of the observed cholinesterase alterations attributed to diazinon dietary intake remain to be determined. PMID- 27383313 TI - Very-low-calorie ketogenic diet with aminoacid supplement versus very low restricted-calorie diet for preserving muscle mass during weight loss: a pilot double-blind study. AB - OBJECTIVE: Obesity plays a relevant pathophysiological role in the development of health problems, arising as result of complex interaction of genetic, nutritional and metabolic factors. We conducted a dietary intervention case-control randomized trial, to compare the effectiveness on body composition of two nutritional protocols: a very-low-carbohydrate ketogenic diet (VLCKD), integrated by an aminoacid supplement with whey protein, and very low restricted-calorie diet (VLCD). PATIENTS AND METHODS: The clinical study was conducted with a randomized case-control in which twenty-five healthy subjects gave informed consent to participate in the interventional study and were evaluated for their health and nutritional status, by anthropometric, and body composition evaluation. RESULTS: The results of this pilot study show that a diet low in carbohydrates, associated with a decreased caloric intake, is effective in weight loss. After VLCKD, versus VLCD, no significant differences in body lean of the trunk, body lean distribution (android and gynoid), total body lean were observed (p > 0.05). After VLCKD, no increasing of sarcopenia frequency, according ASSMI, was observed. DISCUSSION: Many studies have shown the effectiveness of the ketogenic diet on weight loss; even if not know how to work effectively, as some researchers believe that the weight loss is due to reduced calorie intake, satiety could also be induced by the effect of the proteins, rather than the low carbohydrates. CONCLUSIONS: Our pilot study showed that a VLCKD was highly effective in terms of body weight reduction without to induce lean body mass loss, preventing the risk of sarcopenia. Further clinical trials are needed on a larger population and long-term body weight maintenance and risk factors management effects of VLCKD. There is no doubt, however, that a proper dietary approach would impact significantly on the reduction of public expenditure costs, in view of prospective data on increasing the percentage of obese people in our nation. PMID- 27383314 TI - Knowledge, behaviours and attitudes regarding HPV infection and its prevention in female students in West Greece. AB - OBJECTIVE: Infection with several types of human papilloma viruses (HPV) has been correlated with the development of cervical cancer. Apart from other preventive strategies, two prophylactic vaccines have been added recently to the HPV prevention arsenal. The objectives of this study were to assess HPV vaccination coverage rates and to evaluate the level of knowledge regarding cervical cancer, HPV and Papanicolaou test among female students in a Greek city. PATIENTS AND METHODS: A cross-sectional study was carried out among five hundred female students of the Technological Educational Institute (TEI) of Patras, Greece. They completed an eighteen-item self-administrated questionnaire regarding their knowledge related to cervical cancer. RESULTS: Only 31.7% of the students had a high level (> 66%) of total knowledge. The majority (70.4%) had not been vaccinated against HPV. Students who achieved low and moderate total knowledge scores were less likely to be vaccinated against HPV. CONCLUSIONS: Implementing strategies for improving young females' knowledge on the different aspects of the natural course of HPV infection and increasing HPV vaccination coverage rates seem to be crucial. PMID- 27383315 TI - Human Rickettsia aeschlimannii infection: first case with acute hepatitis and review of the literature. AB - OBJECTIVE: Rickettsia conorii is responsible for the Mediterranean Spotted Fever. Recently, new rickettsial species have been recognized in Europe and implicated in human diseases. Clinical features often differ greatly from each other, but non-severe liver involvement is frequently observed during any rickettsial infection. CASE REPORT: We describe the unique case of a patient presented with significant high aminotransferase levels due to the first human R. aeschlimannii infection ever detected in Italy. The hypothesis of rickettsiosis was made on the basis of a comprehensive medical history and was confirmed by serological tests. Molecular analyses made on a sample of hepatic tissue revealed the presence of a rickettsial species never found before in human liver. CONCLUSIONS: A brief review of the literature is reported to highlight how relevant this case is and to remind that rickettsioses should be in the differential diagnoses of acute hepatitis, considering mostly the recent spread of new rickettsial species. PMID- 27383316 TI - Clinical research about airway pressure release ventilation for moderate to severe acute respiratory distress syndrome. AB - OBJECTIVE: To evaluate clinical effects of airway pressure release ventilation (APRV) in patients suffering from moderate to severe acute respiratory distress syndrome (ARDS).e of a patient presented with significant high aminotransferase levels due to the first human R. aeschlimannii infection ever detected in Italy. The hypothesis of rickettsiosis was made on the basis of a comprehensive medical history and was confirmed by serological tests. Molecular analyses made on a sample of hepatic tissue revealed the presence of a rickettsial species never found before in human liver. PATIENTS AND METHODS: From August 2012 to August 2014, fifty-two cases with moderate to severe ARDS were randomly divided into two groups. In the first group (APRV) the airway pressure release ventilation was used; the second group (SIMV) was ventilated using synchronized intermittent mandatory ventilation mode and positive end expiratory pressure (PEEP). Changes in oxygenation index, respiratory mechanics, extravascular lung water, functional residual capacity change and hemodynamics were recorded in both groups after mechanical ventilation. TNF-a and IL-10 levels in alveolar lavage were also measured. Acute physiology and chronic health evaluation (APACHE) II and Murray scores were evaluated. Pneumothorax and mediastinal emphysema during ventilation were also recorded. The probability of survival, the duration of ICU stay, days without organ failure and days without sedation were compared. RESULTS: Conditions in APRV were improved significantly. Oxygenation index was increased, airway peak pressure (Ppeak) was reduced, the lung dynamic compliance improved, extravascular lung water was relieved, functional residual capacity increased and Murray score was improved. In APRV group ventilation central venous pressure (CVP) and systemic circulation resistance index (SVRI) were reduced, but cardiac index (CI) increased, and at the same time lac and oxygen saturation of central venous blood (ScvO2) were improved. Free sedatives days were significantly reduced in APRV group while days without mechanical ventilation were increased and days in ICU were shortened significantly. TNF-alpha and IL-10 concentrations in the alveolar lavage, probability of survival and days without organ failure were similar in both groups. CONCLUSIONS: In patients suffering from moderate to severe ARDS, application of APRV improved lung function and hemodynamics. It also reduced the need for sedatives and the duration of mechanical ventilation as well as days in ICU. PMID- 27383317 TI - Single nucleotide polymorphisms in the promoter region of mir-133a-1 and in pre mir-152 rs1707 may contribute to the risk of asthma in a Chinese Han population. AB - OBJECTIVE: microRNAs (miRNAs) play important roles in the pathogenesis of asthma. Single-nucleotide polymorphisms (SNPs) in the promotor regions of miRNAs or pre miRNAs are involved in the alteration of miRNA expression levels or their maturation process and can contribute to asthma pathogenesis. PATIENTS AND METHODS: A total of 591 asthma cases and 621 controls were recruited for this study to evaluate the genetic effects of the following five single nucleotide polymorphisms (SNPs) on the development of asthma: rs8089787 and rs9948906 in the promoter region of mir-133a-1, pre-mir-499 rs37464444, pre-mir-152 rs1707, pre mir-155 rs5186. The genotypes were determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). RESULTS: Logistic regression analysis revealed that the CT and CT+TT genotypes in the mir 133a-1 rs8089787 (CT vs. CC, OR = 0.413, 95% CI: 0.315-0.541; CT+TT vs. CC, OR = 0.443, 95% CI: 0.342-0.574, respectively) were significantly associated with a decreased risk for asthma in sample of the Chinese Han population, compared with CC genotype. Similarly, the CT and CT+TT genotypes in the mir-133a-1 rs9948906 (CT vs. CC, OR = 0.398, 95% CI: 0.300-0.528; CT+TT vs. CC, OR = 0.403, 95% CI: 0.306-0.532, respectively) were associated with a decreased risk of asthma. However, the C alleles of both mir-133a-1 rs8089787 (C vs. T, OR = 1.867, 95% CI: 1.486-2.345) and rs9948906 (C vs. T, OR = 2.177, 95% CI: 1.690-2.804) were significantly associated with an increased risk for asthma. The CT genotype frequencies of pre-mir-152 rs1707 (CT vs. TT, OR = 4.730, 95% CI: 2.425-9.223) were significantly associated with an increased risk for asthma in a Chinese Han population (p < 0.001). The C allele frequencies of pre-mir-152 rs1707 (C vs. T, OR = 6.671, 95% CI: 3.146-14.147) was also significantly associated with an increased risk of asthma in a Chinese Han population (p < 0.001). However, the genotype and allele frequencies of rs5186, located in pre-miR-155, did not significantly differ between the cases and the controls; as well as those of rs3746444 in pre-miR-499. CONCLUSIONS: Our study provided evidence that polymorphisms of rs8089787 and rs9948906 in the promotor region of mir-133a-1 and pre-mir-152 rs1707 may contribute to the risk of asthma in a Chinese Han population. PMID- 27383318 TI - Correlational study on atmospheric concentrations of fine particulate matter and children cough variant asthma. AB - OBJECTIVE: We explored the relationship between atmospheric concentrations of fine particulate matter and children cough variant asthma. PATIENTS AND METHODS: 48 children all diagnosed with cough variant asthma were placed in the cough asthma group while 50 children suffering from typical asthma were place in typical asthma group. We also had 50 cases of chronic pneumonia (the pneumonia group) and 50 cases of healthy children (the control group). We calculated the average PM 2.5 and temperature values during spring, summer, autumn and winter and monitored serum lymphocyte ratio, CD4+/CD8+T, immunoglobulin IgE, ventilatory index and high-sensitivity C-reactive protein (hs-CRP) levels. RESULTS: Our results showed that PM 2.5 values in spring and winter were remarkably higher compared to other seasons. Correlated analysis demonstrated that the onset of cough asthma group was happening in spring. The onset of typical asthma group happened mostly in winter, followed by spring. We established a positive correlation between the onset of asthma of cough asthma group and PM 2.5 value (r = 0.623, p = 0.017), and there was also a positive correlation between the onset of asthma of typical asthma group and PM 2.5 value (r = 0.714, p = 0.015). Our results showed that lymphocyte ratio and IgE level in the cough asthma group and the typical asthma group were significantly higher. CD4+/CD8+T was significantly lower in the cough asthma group and the typical asthma group. The hs-CRP level in cough asthma, typical asthma and pneumonia groups were significantly higher than that of the control group. The FEV1/predicted value, FEV1/FVC and MMEF/predicted value in the cough asthma group and the typical asthma group were significantly lower than those in other groups, however when comparing between two groups respectively, the difference was not statistically significant. CONCLUSIONS: Our findings showed that PM2.5 was related to the onset of children cough variant asthma. PM2.5 reduced immune regulation and ventilatory function. PMID- 27383319 TI - Comparing classification performance of several types of significant genes to identify key genes in uremia. AB - OBJECTIVE: End-stage renal failure has profound changes in human gene expressions, but the molecular causation of these pleomorphic effects termed uremia is poorly understood. The purpose of this study was to explore key genes in uremia by comparing classification performance of five kinds of significant genes based on the support vector machines (SVM) model. MATERIALS AND METHODS: The five kinds of genes were differentially expressed genes (DEGs), differential pathway genes (DPGs), common differential genes between DEGs and DPGs (CDGs), hub genes (HUGs) and common genes of hub genes and DEGs (CHDGs). In detailed, DEGs were detected by linear models for microarray data (Limma) package. Attract method was utilized to capture DPGs from differential pathways. HUGs were determined according to topological centrality analysis of mutual information network (MIN). Subsequently, SVM model was implemented to assess the classification performance of DEGs, DPGs, CDGs, HUGs and CHDGs, depending on its induces the area under the receiver operating characteristics curve (AUC), true negative rate (TNR), true positive rate (TPR) and the Matthews coefficient correlation classification (MCC). RESULTS: A total of 166 DEGs, 597 DPGs, 13 CDGs, 29 HUGs and 10 CHDGs were obtained in uremia. By assessing the SVM model classification analysis, CHDGs had the best performance of all with AUC = 0.99, TNR = 1.00, TPR = 0.97 and MCC = 0.95. Hence, we considered the CHDGs as key genes in uremia. CONCLUSIONS: Key genes concluded in this investigation might provide vital insights into uremia progression and new therapies. PMID- 27383320 TI - Role of TNF-alpha polymorphism in patients with nickel allergy: a marker of susceptibility to contact polysensitization. AB - OBJECTIVE: Nickel allergy is the most frequent contact allergy in the industrialized country. In allergic contact dermatitis after the presentation of haptenated peptides by resident or newly recruited skin cells, activated CD8+ T cells release IFN-gamma and TNF-alpha, these cytokines are potent activator of keratinocytes. The role of specific cytokines in nickel allergy is not yet fully elucidated. The adenine nucleotide at position -308 in the promoter region of the TNFA gene is associated with an increased production of TNF-alpha, that is a potent activator of keratinocytes. PATIENTS AND METHODS: To evaluate the expression of TNF-alpha polymorphism in patients with allergic contact dermatitis and in healthy people, 41 patients with allergic contact dermatitis to nickel and 40 healthy controls were enrolled. A total of 81 subjects (41 cases and 40 controls) underwent genotyping for the 308 genetic polymorphism in the TNFA gene. RESULTS: The distribution of TNF genotypes TNF-alpha 308 G/A polymorphism in cases didn't differ significantly in the controls group. The genotype GA was present in the 75% of the patients with polysensitization. In one patient was observed the rare genotype A/A. CONCLUSIONS: The carriage of the TNFA-308 A/A and GA genotype may act as a marker of enhanced susceptibility to contact polysensitization, indicating that TNF-alpha is a key regulator of the initiation of delayed-type hypersensitivity reactions, the polymorphism seems to be not enough for the development of nickel monosensitization. PMID- 27383321 TI - Clinical analysis of patients of cirrhosis complicated with adrenal insufficiency. AB - OBJECTIVE: To evaluate the level of cortisol and adrenocorticotrophic hormone (ACTH) in patients with cirrhosis and to investigate the clinical significance and characteristics of cirrhosis with adrenal insufficiency (AI). PATIENTS AND METHODS: A total of 118 patients that were hospitalized in the Department of Gastroenterology of Xiangyang Hospital affiliated to Hubei University due to cirrhosis were selected and chemiluminescence assay was used to measure the basal level of cortisol and ACTH in their blood. All the 118 patients with cirrhosis were divided into two groups, cirrhosis with AI group and cirrhosis without AI group and comparison and analysis of the clinical characteristics and prognosis of the two groups were undertaken. About 39 patients with gastrointestinal polyps were used as control group. RESULTS: The basal level of cortisol of the patient group 329.67+/-136.1 nmol/l was significantly lower than that of the normal control 460.7+/-165.48 nmol/l (p<0.05). Of the 118 patients with cirrhosis, 32 patients had AI (32/118). Compared with the cirrhosis without AI group, cirrhosis with AI group had significantly increased spontaneous bacterial peritonitis (SBP), Child classes, Child scores, MELD scores and case fatality and the difference was statistically significant (p<0.05). The level of albumin and high density lipoprotein-cholesterol (HDL-C) in 32 patients with cirrhosis and AI was significantly reduced and the prevalence rate of facial pigmentation and ascites were significantly higher (p<0.05). But, there was no statistically significant difference between cirrhosis with AI and cirrhosis without AI (p>0.05) in other clinical characteristics and laboratory parameters studied. CONCLUSIONS: The basal level of cortisol in patients with cirrhosis was significantly reduced and about 27% of cirrhosis patients had AI. Patients of the later kind had a higher prevalence rate of SBP, worse hepatic impairment and higher mortality, thus resulting in poor prognosis. PMID- 27383322 TI - Effects of local radiofrequency denervation on ventricular electrophysiological properties in normal and acute myocardial ischemia heart. AB - OBJECTIVE: To observe the effects of local radiofrequency denervation on ventricular effective refractory periods, electrical alternans and ventricular arrhythmia susceptibility post myocardial infarction. MATERIALS AND METHODS: Thirty-four mongrel dogs were randomly divided into the normal heart group (n = 16, 8 in sham and 8 in local sympathetic denervation - LSD) and the acute myocardial ischemia (AMI) group (n = 18, 9 in control and 9 in LSD). The left cardiac sympathetic nerve was denervated with irrigated catheter radiofrequency ablation. Left ventricular effective refractory periods (ERP), monophasic action potential duration at 90% (APD90) and APD alternans were measured at baseline and 2 hours after LSD in the normal heart group. AMI was induced by ligating the left anterior descending coronary artery 2 hours after LSD was performed. Then APD90, the occurrence of ventricular arrhythmias (VAs) were measured. RESULTS: Compared with baseline, LSD significantly prolonged ventricular ERP and APD90 at all sites (p < 0.05 for all) in the LSD group, whereas no significant change was shown in the sham group. But their spatial dispersions did not change in both groups. APD alternans occurred at shorter pacing cycle length at each site after LAD->LSD when compared to the sham group (p < 0.05 for all). After AMI, the occurrence of VAs was significantly lower in the LSD group than in the control group (p < 0.05). CONCLUSIONS: LSD may have a beneficial impact on ventricular arrhythmias induced by AMI through modulation of autonomic tone. PMID- 27383323 TI - Nigella sativa oil and thymoquinone ameliorate albuminuria and renal extracellular matrix accumulation in the experimental diabetic rats. AB - OBJECTIVE: Increasing evidence suggests that Nigella sativa oil (NSO) and its principal bioactive constituents, thymoquinone (TQ), exhibit antioxidant, antihyperglycemic and renoprotective effects in streptozotocin (STZ)-induced diabetes in rats. However, the potential molecular mechanisms by which NSO and TQ may exert their actions in the diabetic kidney are still poorly characterized. This study was designed to investigate the effect of NSO and TQ treatment on the albuminuria, podocyte injury and the complex systems controlling the extracellular matrix proteins accumulation and angiogenesis in the STZ-induced model of diabetic nephropathy. MATERIALS AND METHODS: Adult female Wistar rats were divided into four experimental groups (control, untreated STZ-diabetic, and NSO or TQ treated STZ-diabetic rats). The treated rats received 2 mL/kg NSO or 50 mg/kg TQ via oral gavage once a day for 10 weeks. RESULTS: The results showed that the albuminuria and the kidney weight/body weight ratio were increased in the diabetic rats compared with the control animals and they were significantly ameliorated by the treatment with NSO or TQ. The real-time PCR showed that the NSO and TQ treatment prevented diabetes-induced downregulation of mRNA expression of the podocyte-specific marker (podocin) as well as the mRNA overexpressions of collagen IV, transforming growth factor-beta1 (TGF-beta1) and vascular endothelial growth factor-A (VEGF-A) in the diabetic kidney. These results were also confirmed by immunohistochemistry. CONCLUSIONS: NSO and TQ treatment decreased albuminuria in the experimental models of the diabetic nephropathy by the preservation of the podocyte function; along with the suppression of enhanced extracellular matrix gene expression through interfering with TGF-beta1 production and angiogenesis. PMID- 27383324 TI - The clinical efficacy and safety of levetiracetam add-on therapy for child refractory epilepsy. AB - OBJECTIVE: To investigate the clinical efficacy and safety of Levetiracetam (LEV) add-on therapy for child refractory epilepsy. PATIENTS AND METHODS: Levetiracetam add-on therapy was tested on 65 children who suffered refractory epilepsy, and clinical seizures. Electroencephalogram (EGG) changes and adverse reactions were observed in these children respectively in three, six and twelve months after the therapy. RESULTS: The complete control rates observed after 3, 6 and 12 months were respectively: 6.9%, 10.3% and 3.4%, while the response rates were accordingly 44.8%, 58.6% and 39.6%. The ameliorative rate of EGG reached 65.5%, appearing in positive correlation with the clinical efficacy (r = 0.436, p = 0.001). The retention rate after one year was 89%. Adverse reactions were expressed in 3% of the child patients, and the symptoms were dysphoria, mental and behavior disorders. CONCLUSIONS: The levetiracetam add-on therapy for child refractory epilepsy, demonstrates fast and obvious efficacy as well as fewer adverse reactions. PMID- 27383325 TI - Managing ulcerative colitis in remission phase: usefulness of Casperome(r), an innovative lecithin-based delivery system of Boswellia serrata extract. AB - OBJECTIVE: Boswellia serrata extracts (BSE) have been traditionally used for the treatment of several inflammatory diseases. The aim of this study was to evaluate the efficacy of a novel delivery form of BSE (Casperome(r)) in Ulcerative Colitis (UC) during minimally symptomatic remission phase. PATIENTS AND METHODS: In this open-label, observational, registry study, informed participants with UC in remission phase (n = 43) freely decided to receive the oral daily Casperome(r) supplementation (n = 22) or no supplementation (n = 21) for 4 weeks. Several parameters associated with minimally symptomatic UC in remission were evaluated at the inclusion and the end of the study. RESULTS: A significant beneficial effect of Casperome(r) was observed for all the parameters evaluated, namely: diffuse intestinal pain, evident and occult blood in stools, bowel movements and cramps, watery stools, malaise, anemia, rectal involvement, number of white blood cells as well as need for concomitant drugs and medical attention. Faecal concentration of calprotectin, a marker of bowel inflammation, resulted ameliorated in Casperome(r) supplemented patients. CONCLUSIONS: Our study showed that Casperome(r) supplementation attenuates symptoms associated with mild UC in remission, reducing the use of drugs and medical consultations. Therefore, our study suggests that Casperome(r) supplementation could represent a promising alternative approach to manage minimally symptomatic UC and maintain the remission phase. PMID- 27383326 TI - Adverse events risk associated with angiogenesis inhibitors addition to therapy in ovarian cancer: a meta-analysis of randomized controlled trials. AB - OBJECTIVE: Inhibition of angiogenesis has been regarded as an attractive treatment strategy for advanced or recurrent ovarian cancer. We conduct this meta analysis to investigate the risk of adverse events of special interest related to angiogenesis inhibitors (AIs) in ovarian cancer. PATIENTS AND METHODS: Databases from PubMed, Web of Science and Cochrane library up to December 2015 were searched to identify relevant studies. Eligible studies included prospective randomized controlled phase II/III clinical trials evaluating therapy with or without AIs for ovarian cancer. Summary relative risk (RR) and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects according to the heterogeneity among included trials. RESULTS: A total of 7,761 patients from ten clinical trials were included in the meta-analysis. Pooled RR showed that the use of AIs was associated with a statistically increased risk in four of the adverse outcomes studied: arterial thromboembolic events (RR = 2.0), gastrointestinal (GI) perforation (RR = 3.86), proteinuria (RR = 2.44), and hypertension (RR = 5.39). No statistically significant differences were found for hemorrhagic events (p = 0.07), venous thromboembolic events (p = 0.13), or fatal adverse events (p = 0.26). CONCLUSIONS: The addition of AIs to therapy in ovarian cancer did significantly increase the risk of arterial thromboembolic events, GI perforation, proteinuria and hypertension, but not for venous thromboembolic events, hemorrhagic events, or fatal adverse events. PMID- 27383327 TI - Vitamin E promotes breast cancer cell proliferation by reducing ROS production and p53 expression. AB - OBJECTIVE: The role of antioxidant in cancer cell proliferation is still controversial. This study aimed to explore the effects of antioxidant vitamin E on the proliferation of breast cancer cells and the possible underlying mechanisms. MATERIALS AND METHODS: Orthotopic breast cancer model was established by inoculating MCF7 cells in mice and in vitro MCF7 culture system. CM-H2DCFDA fluorescence probe and Western blot analysis were used to detect ROS changes and p53 expression. p53 knockdown in MCF7 cells by siRNA transfection was also used to determine the combination effect of vitamin E and p53 on MCF7 cell proliferation. RESULTS: Vitamin E supplement in the chow significantly accelerated breast cancer cell growth in vivo. ROS level and p53 expression were decreased in tumor tissues. Water-solvable vitamin E Trolox significantly promoted MCF7 cell proliferation in vitro, while reducing intracellular ROS level and p53 expression. p53 knowdown by p53-siRNA transfection inMCF7 cells significantly reduced p53 expression and increased MCF7 cell proliferation. CONCLUSIONS: Vitamin E accelerated breast cancer growth by reducing ROS production and p53 expression. PMID- 27383328 TI - Clinical application of highly agglutinative staphylococcin in cancer treatment updates of the literature. AB - This review article summarized 100 published research papers and reviewed the application status of highly agglutinative staphylococcin in the clinical treatment of cancer. Highly agglutinative staphylococcin (HAS) derives from the superantigen of Staphylococcus aureus metabolite. Studies have shown that HAS can inhibit and kill tumors, repair tissues and cells, increase white blood cell count and improve the immune function. Its immunological effect acts through the following mechanism: activating T-cells and natural killer cells, enhancing phagocytes' phagocytosis and killing ability of lymphocytes, increasing white blood cell count in peripheral blood, repairing impaired histocytes, and inhibit the growth of tumor cells. Highly agglutinative staphylococcin is used in clinical treatment of tumors: intracavitary hyperthermic perfusion with single HAS is effective for malignant ascites; perfusion with HAS plus chemotherapeutics can remarkably improve the elimination rate of ascites. Highly agglutinative staphylococcin can also enhance the effect of and improve the response rate of chemotherapy and radiotherapy, and improve patients' immune function and relieve gastrointestinal reactions caused by radiotherapy and chemotherapy. Therefore, HAS is used to treat a malignant tumor, leucocytopenia, and malignant ascites, and relieve side effects caused by radiotherapy and chemotherapy and improve patients' immune function. PMID- 27383329 TI - Phosphocreatine attenuates angiotensin II-induced cardiac fibrosis in rat cardiomyocytes through modulation of MAPK and NF-kappaB pathway. AB - OBJECTIVE: Transforming growth factor beta (TGF-beta) plays crucial roles in Ang II-induced cardiac fibrosis (CF). Phosphocreatine (PCr), one of the important players involved in cellular energy metabolism, is widely used in the treatment of clinical heart failure. However, whether it participates in CF is still unclear. This study aimed to identify the mechanisms involved in PCr and CF. MATERIALS AND METHODS: Rat cardiomyocytes (H9C2) were induced by Ang II followed by treatment of PCr. ERK1 siRNA, ERK2 siRNA and NF-kappaB siRNA were applied to identify the molecular mechanism. Then CF-related proteins were analyzed by western blot and real-time PCR to confirm the influence of the mechanisms involved in PCr. RESULTS: PCr did protect cardiomyocytes from Ang II-induced fibrosis. Meanwhile, PCr suppressed Ang II-induced up-regulation of TGF-beta. By detecting TGFbeta-mediated or MAPK pathway associated proteins, PCr inhibited MAPK and NF-kappaB pathway, thus suppressed Ang II-induced cardiac fibrosis, which was further confirmed by siRNA transfection. CONCLUSIONS: Our study determined that PCr protected cardiomyocytes from Ang II-induced CF through inhibition of MAPK and NF-kappaB pathway. PMID- 27383330 TI - Resveratrol exerts protective effects on anoxia/reoxygenation injury in cardiomyocytes via miR-34a/Sirt1 signaling pathway. AB - OBJECTIVE: In this study, we investigated the regulation of resveratrol (RV) on miR-34a alteration due to ARI and further studied the involvement of miR 34a/Sirt1 signaling pathway in ROS generation and cell survival after ARI. MATERIALS AND METHODS: In-vitro anoxia and reoxygenation injury (ARI) model based on rat heart-derived H9c2 cells was established. The expression of miR-34a and Sirt1 in H9c2 cells with or without RV pretreatment was measured. Flow cytometric analysis of intracellular reactive oxygen species (ROS) generation, CCK-8 assay of cell viability and Western blot analysis of active caspase-3 expression were performed to study the role of miR-34a/Sirt1 signaling pathway in RV modulated ARI injury protection. RESULTS: Pretreatment with RV substantially restored Sirt1 expression in cardiomyocytes in a dose-dependent manner in the in-vitro ARI model. MiR-34a level was significantly increased due to ARI. But pretreatment with RV significantly suppressed its upregulation. MiR-34a overexpression significantly reduced the effect of RV on restoring Sirt1 expression in ARI. Both miR-34a overexpression and Sirt1 knockdown significantly reduced the effect of RV on reducing ROS generation and also abrogated the effect of RV on enhancing cell viability and reducing cell apoptosis. CONCLUSIONS: The present study demonstrated that RV has a suppressive effect on miR-34a upregulation in ARI and the miR-34a/Sirt1 axis is an important signaling pathway modulating the protective effect of RV on cardiomyocytes in ARI. Nonetheless, future in vivo studies are required to validate this mechanism. PMID- 27383331 TI - Tribenoside and lidocaine in the local treatment of hemorrhoids: an overview of clinical evidence. AB - OBJECTIVE: The combination of tribenoside+lidocaine (Procto-Glyvenol(r)) is a medical preparation for the local treatment of hemorrhoids, delivered as a suppository or rectal cream. This product has been used for decades in the therapy of hemorrhoids. This review discusses available evidence on the use of tribenoside/lidocaine in clinical practice. MATERIALS AND METHODS: Papers were retrieved by a PubMed search, using different combinations of pertinent keywords (e.g. tribenoside AND hemorrhoids), without any limitations in terms of publication date and language. Documents from Authors' personal collection of literature could also be considered. Papers were selected for inclusion according to their relevance for the topic, as judged by the Authors. RESULTS: The efficacy of the combination of tribenoside+lidocaine in relieving symptoms caused by hemorrhoids and its safety have been assessed in several clinical studies on patients of either gender, either versus its two individual components (tribenoside and lidocaine) or versus steroids in the same setting. Five studies compared the combination treatment with each of its single components, and of these, three studies compared tribenoside+ lidocaine with a tribenoside-free semi placebo preparation containing only lidocaine, and two studies compared this combination with lidocaine-free preparations containing only tribenoside. Tribenoside+lidocaine was compared with steroid-containing preparations in six studies. Last, two studies evaluated the efficacy and tolerability of the tribenoside+lidocaine combination in women with hemorrhoids as a consequence of pregnancy or delivery. All the above-mentioned studies were well-conducted and can provide a comprehensive evaluation of tribenoside+lidocaine in the treatment of hemorrhoids. CONCLUSIONS: Enough evidence exists to recommend the use of this combination therapy as a fast, effective and safe option for the local treatment of low-grade hemorrhoids. PMID- 27383332 TI - Metal-Catalyzed Cyclization Reactions of 2,3,4-Trien-1-ols: A Joint Experimental Computational Study. AB - Controlled preparation of tri- and tetrasubstituted furans, as well as carbazoles has been achieved through chemo- and regioselective metal-catalyzed cyclization reactions of cumulenic alcohols. The gold- and palladium-catalyzed cycloisomerization reactions of cumulenols, including indole-tethered 2,3,4-trien 1-ols, to trisubstituted furans was effective, due to a 5-endo-dig oxycyclization by attack of the hydroxy group onto the central cumulene double bond. In contrast, palladium-catalyzed heterocyclization/coupling reactions with 3 bromoprop-1-enes furnished tetrasubstituted furans. Also studied was the palladium-catalyzed cyclization/coupling sequence involving protected indole tethered 2,3,4-trien-1-ols and 3-bromoprop-1-enes that exclusively generated trisubstituted carbazole derivatives. These results could be explained through a selective 6-endo-dig cumulenic hydroarylation, followed by aromatization. DFT calculations were carried out to understand this difference in reactivity. PMID- 27383333 TI - The reality of health in prisons and the challenges involved. PMID- 27383334 TI - Demography, vulnerabilities and right to health to Brazilian prison population. AB - This study investigates the latest research on the profile of the Brazilian prison population, its demography and current laws and regulations. It aims in the direction of ensuring the human right to health. Brazilian prison system is a complex universe in which state and federal criminal contexts keep more than 607,000 people in custody. This population is composed of 75% of young and black people, 67% poorly educated and 41% are pre-trial detainees, living in overcrowded prisons and architecturally vandalized, with population growth of around 575% in 24 years, making this environment a major focus of production of diseases. The prison becomes the object of differentiated intervention by public bodies linked to the executive and the judiciary - it is worth remarking that the data show the high level of inequalities and health vulnerabilities among the prison population, whose needs involve a set of cross-sector of transverse public policies actions towards penal execution. PMID- 27383335 TI - [Not Available]. PMID- 27383336 TI - Emergence of a Policy, closure of a sector: regarding the management of penitentiary health care in Brazil. AB - The aim of this study is to understand recent transformations in penitentiary health care management in Brazil, during the implementation of the National Policy for Comprehensive Health Care for People Deprived of Liberty in the Prison System, and the closure of the National Sector for Penitentiary Health Care. The scientific problem investigated is the language of penitentiary health care policy. The theoretical-methodological framework adopted is Pierre Bourdieu's genetic structuralism. In this manner, we carry out an analysis of documents and public statements in search of State categories and classifications. We note the consolidation of a state classification that separates the 'penitentiary' domain from the 'prison' domain, as well as the creation of the State category of 'person deprived of liberty in the prison system'. Penitentiary health care management constitutes itself as a question of primary care. PMID- 27383337 TI - Health conditions of prisoners in the state of Rio de Janeiro, Brazil. AB - We present the results of a quantitative and qualitative study on the living conditions and health of prisoners in the state of Rio de Janeiro. The goal was to produce strategic information to support the action of public officials who work in prisons. The results show that prisoners are young (average age: 30 years), poor, mostly black and brown (70.5%), have little education (only 1.5% of them have a higher education), and have been in prison for less than four years. Among the problems that indirectly affect their health, we emphasize: overcrowding (1.39 prisoners per one vacancy), idleness (only 4.4% of them work), lack of perspective, violence and relationships of conflict. The most common physical health problems include: musculoskeletal problems, such as pain in the neck, back, and spine (76.7%), joint dislocation (28.2%), bursitis (22.9%), sciatica (22, 1%), arthritis (15.9%), bone fracture (15.3%), problems with bone and cartilage (12.5%), and muscle and tendon injuries (15.7%); respiratory problems, such as sinusitis (55.6%), allergic rhinitis (47%), chronic bronchitis (15.6%), tuberculosis (4.7%) and others (11.9%); and skin diseases. Despite legal requirements that include prison health care among the Universal Health System's (SUS) obligations, services are scarce and inefficient and a major cause of inmate dissatisfaction. PMID- 27383338 TI - Women's reproductive rights in the penitentiary system: tensions and challenges in the transformation of reality. AB - This article seeks to identify and discuss violations and challenges to the fulfillment of women's reproductive rights in situations of deprivation of liberty, with an emphasis on sexual and reproductive health. Regulatory parameters were considered as analytical frameworks that support these rights identified by the literature, and the discourses and practices linked to their effectiveness in the everyday life of prisons, collected in interviews with pregnant women and children in prisons, and the professionals whose practices interfere with the exercise of these rights. It was discovered that violations of these rights find support in speech that delegitimizes the motherhood of these women. We consider the use of rights as strategic in the struggle for the transformation of this situation. PMID- 27383339 TI - Health issues of incarcerated women in the United States. AB - Health care within jails and prisons in the United States is typically insufficient to meet the medical and psychological needs of female inmates. Health services are often of low quality, especially in the areas of reproductive medicine. Mental illness, substance abuse, a trauma history, and sexual victimization while incarcerated can predict a more difficult adjustment to a correctional environment. Incarcerated women who are able to maintain contact with family members, especially children, can have a better prison adjustment. Recommendations are made to improve the types and quality of health care delivered to women in jails and prisons in countries around the world. PMID- 27383340 TI - Birth in prison: pregnancy and birth behind bars in Brazil. AB - The high vulnerability of incarcerated women is worsened when they are pregnant and give birth during imprisonment. This article traces the profile of incarcerated women living with their children in female prison units of the capitals and metropolitan regions of Brazil and describes pregnancy and childbirth conditions and healthcare practices while in incarceration. This study is an analysis of a series of cases resultant from a national census conducted between August 2012 and January 2014. This analysis included 241 mothers. Of these, 45% were younger than 25 years old, 57% were dark skinned, 53% had studied less than eight years and 83% were multiparous. At the time of incarceration, 89% were already pregnant and two thirds did not want the current pregnancy. Access to prenatal care was inadequate for 36% of the women. During their hospital stay, 15% referred to having suffered some type of violence (verbal, psychological, or physical). Only 15% of the mothers rated the care received during their hospital stay as excellent. They had low social/familial support and more than one third reported the use of handcuffs during their hospital stay. Incarcerated mothers received poorer healthcare during pregnancy and birth when compared with non incarcerated users of the public sector. This study also found violations of human rights, especially during birth. PMID- 27383341 TI - Tuberculosis control in prisons, from research to action: the Rio de Janeiro, Brazil, experience. AB - The high tuberculosis (TB) rates observed in the Brazilian prison population highlights the need for more efficient TB control measures in this population, especially in the state of Rio de Janeiro where detection rates are 30 times higher than in the general population. We present results of epidemiological, biomathematics modelling, molecular biology, psychosocological, architectural and juridical studies carried out in this state in order to assess the situation and to develop TB control strategies adapted to the specificities of the prison context. The implementation of these strategies implies to take into account the day-to-day realty of prison life and to turn more effective the supervision of the prison health system by instances in charge of monitoring the fulfillment of sentences, so as to guarantee access of prisoners to health in conformity with international and national laws. PMID- 27383342 TI - Drug use in prisons: strategies for harm reduction (ANRS-PRIDE Program). AB - The existence of risky practices related to drug use inside prisons is a reality everywhere and is a major issue for the community as a whole. The level of implementation of harm reduction (HR) measures recommended by the World Health Organization (WHO) and the United Nations Office on Drugs and Crime (UNODC) is very often poor and reveals inadequate concern about public health issues in the prison environment, without any respect for the principle of equivalence for prevention and health assistance with the general community. In 2009, the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) developed a comprehensive research program focusing on the prevention of infectious risks in prison settings. Different steps were defined and scheduled, and included i) an inventory of harm reduction (HR) measures, ii) a qualitative survey on the reality of risky practices, iii) an assessment of the social acceptability of HR measures, and iv) an intervention trial exploring the feasibility of upgrading existing HR strategies. A progressive implementation of this program has shown it is feasible, but in France, it requires tenacity, simple long-term objectives, support from a scientific authority, pedagogical interventions for all involved, as well as constant discussion with the authorities. The implementation of this program in other countries is equally simple to manage. PMID- 27383343 TI - The impact of prisons on the mental health of prisoners in the state of Rio de Janeiro, Brazil. AB - The aim of this article is to assess the mental health status of inmates and people in custody in the state of Rio de Janeiro and the association between mental health and imprisonment using the Beck Depression Inventory and the Lipp Stress Symptom Inventory for Adults. SAMPLE: 1,573 individuals, via stratified sampling with probability proportional to size. STUDY POPULATION: more than half have up to 29 years old; 70.6% were black/brown; 77.4% had strong family ties; 42.9% had been incarcerated for under a year; and 22,9% performed work tasks in prison. Stress: 35.8% of men and 57.9% of women. Factors associated with stress among men: length of time in prison and family ties. Male prisoners who had been in prison for between 1 and 9 years are 0.55 times less likely to experience stress symptoms than those who had been in prison for less than a year; those with regular/weak family ties are more likely to experience stress than those with strong ties. Women with only regular/weak family ties are more likely to experience stress; work tasks performed in prison was a protective factor. Depression: 7.5% of women and 6.3% of men. Among men, practicing a religion, maintaining strong family ties, and performing prison work tasks are protective factors. Among women, an association was found between depression and family ties. PMID- 27383344 TI - Right to mental health in prison system: reflections on the process of deinstitutionalization of the HCTP. AB - This study aimed to discuss the close relationship between mental health, the criminal justice system and the prison system, whose specific interfaces are the HCTP (Hospital de Custodia e Tratamento Psiquiatrico, or Judicial Psychiatric Hospital) conflict and the person with mental disorder in conflict with the law. There will be presented extensive discussions on the Penal Execution Law and the Brazilian Psychiatric Reform Law, as well as cross-sector actions taken by the judiciary and the federal government (Brazilian National Health System - SUS and National Social Assistance System - SUAS) to bring the criminal justice system and the prison system to the anti-asylum combat. Two successful experiences in the states of Minas Gerais and Goias will also be presented for they reflect the emergence of a new strategy on public health policy: The Evaluation Service and Monitoring Therapeutic Measures for the Person with Mental Disorder in Conflict with the Law, device connector between systems, willing to operate in the process of deinstitutionalization of people with mental disorders of HCPT. PMID- 27383345 TI - [The process of detection and treatment of cases of tuberculosis in a prison]. AB - This study seeks to analyze the process of detection and treatment of cases of tuberculosis (TB) in a prison in the south of Brazil. An active and passive search for TB was conducted to estimate the scale of TB in a prison with 764 inmates. In conjunction with the detection strategies and clinical follow-up of the 41 TB cases, participant observation and records in field diaries were performed, making it possible to analyze the scope and limitations of detection and treatment of cases of TB in prison. The development of search strategies is discussed along with the use of questionnaires to detect symptomatic cases, as well as the inadequacy of the clinical follow-up of TB cases, involvement of different workers and coordination between prison and health services. There is clear potential for the control of TB using an active search to induce the passive detection and screening for symptoms that - even skewed by the perceptions of inmates regarding symptoms of TB - enabled an increase in detection. The functional dynamics of prison life hamper the inclusion of health routines and can restrict actions to control TB and other diseases. In the process of control of TB in prisons, the feasibility of effective detection methods is as important as planning based on disease conditions, network services and workers involved. PMID- 27383346 TI - [Families of incarcerated women, health promotion and access to social policies in the Federal District, Brazil]. AB - This paper assesses the options for accessing public policies available to families of women incarcerated in the female penitentiary of Brazil's Federal District. It seeks to contribute to the construction of health promotion strategies for the female population living in the prison system. Some of the claims were revealed in the national comprehensive healthcare policy for individuals in the prison system, especially those that acknowledge the importance of intersectoral actions and relationship networks to promote health. Data are presented from research conducted at the penitentiary in 2014 that used qualitative methodology by means of participant observation and semi-structured interviews with family members of women incarcerated in the Federal District. It was detected that attention must be paid to the different types of relationship that exist between incarcerated women and their families, and especially to the allegations of exhaustion and difficulty of access to public policies. A more in depth survey into how this population organizes itself could assist in the development of public policies to promote health and overcome social vulnerability. PMID- 27383347 TI - Psychological distress and work stress in correctional officers: a literature review. AB - This article presents a review of literature based on a survey of national and international journals on psychological distress and stress in the work of correctional officers between 2000 and 2014. The databases used were the Biblioteca Virtual em Saude, Web of Science, and Scopus, and the descriptors were psychological distress, stress and correctional officers. We analyzed 40 articles, mainly about stress. The concept of burnout appeared in several works. The United States is the country that most publishes on the subject. There is little interest about the subject in the journals of Public Health. In Latin America we found only four studies, all Brazilian. The number of publications has gradually intensified over the years, and there was methodological improvement in the development and assessment scales, mainly regarding stress and burnout. Work overload, lack of material and human resources, level of contact with the inmates, overcrowding, perceptions of fear or danger, and the paradox of punish / reeducate were some of the risk factors encountered, among others. The protective factors refer to social support within the prison environment, and the coping strategies are related to the improvement of officer training, stimulating social support, and offering psychological care. PMID- 27383348 TI - [Not Available]. AB - The scope of this study was to organize the knowledge produced on tuberculosis in Brazilian prisons in a systematic manner. A comprehensive review was conducted in the Medline and Lilacs databases and the SciELO electronic library using the key words: "Tuberculosis," "Prisons" and "Brazil." Of the 61 records found, 33 were evaluated (28 duplicated records) and 21 included in the review (12 excluded according to the criteria adopted). These studies contribute effectively to improve the knowledge regarding the scale of the disease among inmates, as well as to the choice of screening and diagnostic methods most appropriate to the prison setting. The incidence rates and prevalence of active and latent tuberculosis are presented, in addition to data on the profile of drug and genotype susceptibility of the clinical results. Awareness of the data presented highlights the need to adopt measures aimed at case detection, treatment and follow-up. It is suggested that the new challenges for scientific research should be linked to the development of specific knowledge about dealing with the problem in an environment full of specificities such as a prison. PMID- 27383349 TI - [The actions of the Public Prosecution Service in the field of health in prisons]. AB - In the violent, insalubrious and overpopulated prison environment in which the concerns of penitentiary managers are predominantly focused on security, several actors of the legal world work incessantly to ensure that prisoners enjoy living conditions and access to health care in accordance with their constitutional rights. However, their discourses only appear infrequently in academic research and studies on health in prisons. We decided to ask for the opinion of a District Attorney of the State Public Prosecution Office, Dr. Erika Puppim to share with readers her view and the difficulties in her role in the protection of prisoners. PMID- 27383350 TI - [Disintegration of the prison system, public security and social exclusion]. AB - The defense of human rights, namely one of the most important duties of the legislature, is a considerable challenge in the day-to-day business of parliament. The opinions and practices of elected representatives reflect the security concerns and fears of society that engender a vast process of social exclusion. In this context, the defense of the right to health of persons deprived of liberty seems an especially difficult task, as shown in the interview of State Congressman Marcelo Freixo, the Coordinator of the Human Rights Commission of the Legislative Assembly in Rio de Janeiro and creator of the State Mechanism for Preventing and Combating Torture. PMID- 27383351 TI - The impact of insecticides management linked with resistance expression in Anopheles spp. populations. AB - The resistance of some species of Anopheles to chemical insecticides is spreading quickly throughout the world and has hindered the actions of prevention and control of malaria. The main mechanism responsible for resistance in these insects appears to be the target site known as knock-down resistance (kdr), which causes mutations in the sodium channel. Even so, many countries have made significant progress in the prevention of malaria, focusing largely on vector control through long-lasting insecticide nets (LLINs), indoor residual spraying and (IRS) of insecticides. The objective of this review is to contribute with information on the more applied insecticides for the control of the main vectors of malaria, its effects, and the different mechanisms of resistance. Currently it is necessary to look for others alternatives, e.g. biological control and products derived from plants and fungi, by using other organisms as a possible regulator of the populations of malaria vectors in critical outbreaks. PMID- 27383352 TI - Mobile prehospital emergency care: an analysis of implementation in the State of Rio de Janeiro, Brazil. AB - Mobile prehospital care is a key component of emergency care. The aim of this study was to analyze the implementation of the State of Rio de Janeiro's Mobile Emergency Medical Service (SAMU, acronym in Portuguese). The methodology employed included document analysis, visits to six SAMU emergency call centers, and semistructured interviews conducted with 12 local and state emergency care coordinators. The study's conceptual framework was based on Giddens' theory of structuration. Intergovernmental conflicts were observed between the state and municipal governments, and between municipal governments. Despite the shortage of hospital beds, the SAMUs in periphery regions were better integrated with the emergency care network than the metropolitan SAMUs. The steering committees were not very active and weaknesses were observed relating to the limited role played by the state government in funding, management, and monitoring. It was concluded that the SAMU implementation process in the state was marked by political tensions and management and coordination weaknesses. As a result, serious drawbacks remain in the coordination of the SAMU with the other health services and the regionalization of emergency care in the state. PMID- 27383353 TI - Prevalence of suggestive images of carotid artery calcifications on panoramic radiographs and its relationship with predisposing factors. AB - Panoramic radiographs (PR) can display radiopaque images suggestive of calcified atheroma in the carotid artery in asymptomatic patients. The aim of this study was to evaluate the prevalence of these images on PR and their linkage with hypertension, obesity, age, gender and smoking habits. PR of 505 patients were evaluated. They were older than 30 years old and their PR had been taken for different clinical reasons. Their body mass index was calculated; their waist circumference was also taken into consideration. Information about smoking habits and hypertension was obtained. The observers analyzed the presence of radiopaque mass in the region of the cervical vertebrae C3-C4 through the PR, confirmed by an antero-posterior (AP) radiograph. The results showed a 7.92% prevalence of suggestive images of calcifications on PR and on AP radiograph. The adjusted Odds Ratio showed association with age and smoking habits. The calcification process is almost nine times higher for the elderly when compared to the young. As far as smokers are concerned, this process is twice worse when compared to no smokers. In conclusion, 7.92% of the group studied presented suggestive images of carotid atherosclerosis on PR, which is directly associated with the age and smoking habits. PMID- 27383354 TI - Food intake and the nutritional status of women undergoing chemotherapy. AB - The objective behind this study was the analysis of food intake and the nutritional status of women with breast cancer (BC) undergoing chemotherapy (CT). The quantitative dietary evaluation was performed in accordance with Dietary Reference Intakes (DRI), whereas the qualitative evaluation was performed through the Brazilian Healthy Eating Index - Revised (BHEI-R).From among the total number of patients (n = 20), 60% (n = 12) presented waist circumference, equal to or higher than 88cm. It was noted that 75% (n = 15) individuals were overweight. The average intake for calcium, copper, iron, dietary fiber, magnesium, potassium, vitamin A, niacin, vitamin B6 and zinc, were found to be below adequate intake levels, while the intake of vitamin C, phosphorus, manganese, sodium and thiamine were all found to be above DRIs recommendations. As for the analysis of the BHEI R, 80% (n = 16) of the patients presented a "diet that needs modifications", while 20% (n = 4) presented a "healthy diet". Noted from these observations was the presence of a high overweight rate, a discrepancy in the intake of micronutrients and a diet that needed improvements. In this manner, the establishment and use of a nutritional intervention protocol are very important when it comes to the improvement of the diet in patients with BC and who are undergoing CT. PMID- 27383355 TI - [Anthropometric indices of children treated in daycare centers and the relationship with socioeconomic, maternal and child factors]. AB - Weight/height and weight/age anthropometric statistics are important, respectively, for identifying incipient changes in weight and alterations in nutritional status at an early stage. The scope of this study was to analyze weight/height- and weight/age-associated factors in preschool children. This is a cross-sectional study with a probabilistic sample scrutinizing 299 children enrolled in municipal daycare centers. Information was obtained through interviews with mothers together with a questionnaire analyzing socioeconomic, maternal and child information. Weight and height/stature of children were measured according to recommendations of the World Health Organization. The results showed that none of the maternal variables was associated with the nutritional status of children and that only birth weight among child variables revealed any association with weight/height (p = 0.0030) and weight/age scores (p = 0.0018). The block of socioeconomic variables, in turn, proved to be the most representative variation factor of results, especially in the weight/age index. The importance of birth weight in the weight/height and weight/age of children, as well as the socioeconomic conditions notably in weight/age indices, was clearly revealed. PMID- 27383356 TI - Cultural adaptation of the Tuberculosis-related stigma scale to Brazil. AB - The process of stigmatization associated with TB has been undervalued in national research as this social aspect is important in the control of the disease, especially in marginalized populations. This paper introduces the stages of the process of cultural adaptation in Brazil of the Tuberculosis-related stigma scale for TB patients. It is a methodological study in which the items of the scale were translated and back-translated with semantic validation with 15 individuals of the target population. After translation, the reconciled back-translated version was compared with the original version by the project coordinator in Southern Thailand, who approved the final version in Brazilian Portuguese. The results of the semantic validation conducted with TB patients enable the identification that, in general, the scale was well accepted and easily understood by the participants. PMID- 27383357 TI - [Semantic and conceptual equivalence of the observable indicatorsof Nursing Home Care Quality Instrument]. AB - Long-term care facilities (LTCFs) for the elderly are an important health care alternative in the world, though Brazil does not yet have a valid instrument to monitor the quality of these institutions. This study sought to describe the initial stages of the cross-cultural adaptation of the Observable Indicators of Nursing Home Care Quality (OIQ) instrument used to assess the quality of care in LTCFs. Conceptual equivalence was conducted to assess the relevance and feasibility of the OIQ within the Brazilian context, using the Content Validity Index (CVI). The operational, idiomatic and semantic equivalence was then performed. This item consisted of 5 phases: (1) two translations; (2) the respective back translations; (3) formal appraisal; (4) review; and (5) application of the pre-test in three LTCFs. Significant changes were made to ensure the validity of the OIQ. The CVI instrument for the Brazilian contextwas 94.3% (viability) and 95.3% (relevance). The OIQ proved to be easy to understand and apply in the pre-test. Cross-cultural adaptation of the OIQ contributes to assessing and improving quality in Brazilian LTCFs, though the findings should be complemented by a psychometric evaluation of the instrument. PMID- 27383358 TI - Stunting in children under five years old is still a health problem in the Western Brazilian Amazon: a population-based study in Assis Brasil, Acre, Brazil. AB - Despite the process of nutritional transition in Brazil, in some places, such as the Amazon region, stunting is still an important public health problem. We identified the prevalence and factors associated with stunting in children under five years old residing in the urban area of Assis Brasil. A survey was conducted in which a questionnaire on socioeconomic, maternal and children's conditions was applied, and height or length was measured. The children with height for age index below -2 Z-scores were considered stunted, according to the criteria by the World Health Organization. Four hundred and twenty-eight children were evaluated. Of these, 62 were stunted. Factors associated with stunting, according to adjusted models, were: the presence of open sewer, the wealth index for households, the receipt of governmental financial aid and the mother's height, age and education. Therefore, it was observed that family and the mother's characteristics as well as environmental and socioeconomic factors were closely related to the occurrence of stunting in the population studied, and such nutritional disturbance is still a health problem in the Brazilian Amazon. PMID- 27383359 TI - [Level of awareness and the adequate application of sunscreen by beauticians]. AB - The scope of this research was to establish the level of awareness of beauticians regarding the importance of the application of sunscreen and to identify whether their patients had been properly instructed by these professionals. It involved a descriptive and exploratory study with interviews applying qualitative methodology among 30 beauticians. Data were gathered using the semi-structured interview technique in Maringa, in the southern state of Parana. The data were analyzed using Atlas.ti software after applying quantitative analysis and response classification. Of those interviewed, 83.33% had a degree in Aesthetics, 20% attended ongoing training activities on sunscreen and 73.17% acquired sunscreen for its quality, though 86.67% were not familiar with sunscreens with natural anti-free radical components. Of those interviewed, 80% had never treated patients with skin cancer, though they reported having knowledge of care in relation to sun exposure and how to use the sunscreen and the relationship of these practices with the disease. The results showed that the recommendations and use of sunscreen by beauticians and users has been conducted in an adequate and conscientious manner. PMID- 27383360 TI - [Food insecurity and inadequate food intake among students of municipal schools, Sao Leopoldo, state of Rio Grande do Sul, Brazil]. AB - This research involves a school-based cross sectional study to evaluate the association between food insecurity (FI) and inadequate food intake (IFI), among 782 children (mean age of 6.9+/-0.5) of the 1st year of primary school in the municipal schools of Sao Leopoldo in the state of Rio Grande do Sul. Data were gathered from mothers or guardians. FI was obtained through the Brazilian Food Insecurity Scale, and food consumption using the food frequency questionnaire. Foods were classified as healthy eating markers (HEM) and unhealthy (UEM) and received scores according to intake frequency. HEM: 0 - 1 day - zero; 2 to 3 days - 0.25; 4 to 5 days - 0.75; 6 to 7 days - 1, and the reverse for the UEM. The scores could range from 0 to 25 (HEMS) and 0 to 19 (UEMS). A standardized total score (TS) was obtained [HEMS * (19/44) + UEMS * (25/44)] and could range from 0 to 22. The scores were categorized into terciles and the 1st considered IFI. The FI was 45.1% and the average scores were 5.9 (HEMS), 15.9 (UEMS) and 11.6 (TS). No association was found between IA and IFI. High IA and low food scores require intersectoral approaches to ensure access to food in quantity and quality appropriate for this population. PMID- 27383361 TI - [Immunization coverage and associated factors of women who have recently given birth in a city in Sao Paulo state]. AB - The importance of immunization among actions recommended in the prenatal period raises the possibility of protecting both the mother and the fetus against certain harmful diseases. The scope of this study was to assess the immunization coverage and associated factors of mothers whose deliveries occurred in the first half of 2012 in Botucatu, state of Sao Paulo. It is a cross-sectional study and data collection was performed in the two municipal maternity hospitals. Of the total births during the study period, 1318 mothers (90.3%) were included The data for the characterization of participants and their vaccination status (diphtheria, tetanus and hepatitis B) were obtained from the prenatal card, hospital records or interviews. For analysis of associated factors, the Chi square test was used, with a 95% confidence interval and critical p of <0.05. Most of the study participants were 20 years old or more (84.4%), had seven years of schooling (69%), were monitored in prenatal care (99.2%) with seven or more appointments (88.9%). Miscarriage and infant death of 17.7% and 2.4% was recorded, respectively. Vaccination coverage was 68.4%. There was no association between sociodemographic and obstetric variables relating to prenatal care and vaccination of pregnant women. PMID- 27383362 TI - Knowledge of triatomine insects and of the Chagas disease among people from localities which have different levels of vector infestations. AB - Community participation is the main strategy to sustainability of Chagas disease entomological surveillance. The purpose of this study was to evaluate the level of knowledge on triatomine insects and Chagas disease among the residents from eight localities of Diamantina, in Minas Gerais, with a view to observing any associations between their knowledge and infestations by triatomines. In order to evaluate this knowledge, questionnaires were used containing both closed and open questions. They were applied to 583 residents who were ten years old or over. To establish if they could recognize the triatomine insect, they were given samples to look at. The responses to the closed questions were analyzed with reference to any frequencies of and associations with infestations involving this insect. The responses to the questions were organized into different thematic areas and were descriptively analyzed. Although the resident's ability to recognize the triatomine insect was not associated with the infestation of the localities, the residents in the areas that had higher infestations showed that they had a good knowledge of the available support services and the need to send the insects to them. We did not observe any associations between triatomine infestations and knowledge of Chagas disease. The results of this study can provide guidance on education that can be given by the health services to the community in order to encourage them to provide notifications of the triatomine insects. PMID- 27383364 TI - [Deserdados sociais: condicoes de vida e saude dos presos do estado do Rio de Janeiro. Rio de Janeiro]. PMID- 27383363 TI - Recording actions to prevent child morbidity in children's health cards. AB - The aim of this study was to analyze the registering of preventative actions in relation to child morbidity using information regarding vaccinations, as well as iron and vitamin A supplements, which are recorded in children's health cards. This transversal study used a quantitative approach and was performed in Family Health Units in the city of Joao Pessoa, Paraiba; the sampling was by convenience and totaled 116 children's health cards. The data was collected by observing the cards and the analysis was simple, statistical. The highest percentage of children had their vaccination cards up to date (92.2%) and those that did not were aged between 6 and 12 months: 78.9% of the cards did not have records relating to iron and vitamin A supplements and others only had records of one of the supplements being administered. The vaccination status of children in the first year of life was found to be satisfactory; however, discrepancies were observed in the recordings of the administration of iron and vitamin A supplements, which complicates monitoring performed by child health care professionals. It is hoped that this study will contribute to discussions and strategies aimed at improving the monitoring and recording of micronutrients in children's health cards. PMID- 27383365 TI - [Saude penitenciaria no Brasil: plano e politica]. PMID- 27383366 TI - Errata. AB - [This corrects the article DOI: 10.1590/1413-81232015214.07922015.] [This corrects the article doi: 10.1590/1413-81232015215.00332015]. PMID- 27383367 TI - Molecular mechanics of the cooperative adsorption of a Pro-Hyp-Gly tripeptide on a hydroxylated rutile TiO2(110) surface mediated by calcium ions. AB - The interaction of amino acids with inorganic materials at interfaces plays an important role in enhancing the biocompatibility of titanium-based alloys. The adsorption of a tripeptide, i.e. Pro-Hyp-Gly, on the hydroxylated rutile TiO2(110) surface was investigated by the MD simulations. The changes in free energy during the adsorption of both the tripeptide and calcium ions were calculated by using the PMF method in order to obtain the adsorption strength. The results suggested that the adsorption of the tripeptide on the TiO2 surface through the carboxyl groups in glycine residues can be more stable compared with other binding conformations. Special attention was focused on the cooperative adsorption of the tripeptide with the assistance of calcium ions. Calcium ions preferred to absorb at the tetradentate or monodentate sites on the negatively charged TiO2 surface. As a result of the strong attraction between the carboxyl group and calcium ions, the tripeptide can be pulled down to the surface by following the trajectory of the calcium ions, forming an indirect interaction with a sandwich structure of peptide-cation-TiO2. However, this indirect interaction could eventually transform to the direct adsorption of the tripeptide on the TiO2 surface with higher binding energy. The results may help to interpret the adsorption of peptides on inorganic materials in aqueous solution with ions. PMID- 27383368 TI - Synthesis and Evaluation of Biotinylated Bivalent HistoBlood Group Antigens for Capturing Human Noroviruses. AB - A panel of biotinylated bivalent H-type glycans that have been reported as binding ligands for human noroviruses were synthesized using a modular synthetic strategy. These glycoconjugates were attached to streptavidin-coated magnetic beads and used to recover human norovirus from fecal samples using a magnetic bead-based assay. The biotinylated bivalent glycans synthesized for this study exhibited similar or better capturing ability when compared to commercial biotinylated glycopolymers. PMID- 27383369 TI - Direct total body 214Bi measurements and their implications for radon dose assessment. AB - Direct 214Bi bioassays may elucidate some of the uncertainties related to the relationship between the ambient concentration of radon and its short-lived decay products and the corresponding radiation burdens of individual human subjects. Sequential total body 214Bi activity measurements were carried out on a group of 67 healthy adult volunteers living in a region with moderate airborne radioactivity and conducting similar daily activities using a whole-body counter equipped with sixteen NaI(Tl) detectors. The total body 214Bi activity in the studied subjects was related to gender, fat-free mass and the season of the year. Approximately 95% and 92% of the 214Bi activity measured during the cold seasons of the year in men and women, respectively, was attributed to radon progeny inhalation. Following acute exposure to high airborne radioactivity over a short time period, the 214Bi enhancement in a volunteer decreased exponentially with time post-exposure, with a half-time of about 40 min. Taking into account the anticipated low 214Bi activity in the vast majority of individuals, and the uncertainties in 214Bi biodistribution even during counting, accurate measurements can be obtained using high-sensitivity whole-body counters with almost geometrical invariant counting efficiency. PMID- 27383370 TI - Minireview: Syndecans and their crucial roles during tissue regeneration. AB - Syndecans are transmembrane heparan sulfate proteoglycans, with roles in development, tumorigenesis and inflammation, and growing evidence for involvement in tissue regeneration. This is a fast developing field with the prospect of utilizing tissue engineering and biomaterials in novel therapies. Syndecan receptors are not only ubiquitous in mammalian tissues, regulating cell adhesion, migration, proliferation, and differentiation through independent signaling but also working alongside other receptors. Their importance is highlighted by an ability to interact with a diverse array of ligands, including extracellular matrix glycoproteins, growth factors, morphogens, and cytokines that are important regulators of regeneration. We also discuss the potential for syndecans to regulate stem cell properties, and suggest that understanding these proteoglycans is relevant to exploiting cell, tissue, and materials technologies. PMID- 27383371 TI - Pathogenesis of Streptococcus urinary tract infection depends on bacterial strain and beta-hemolysin/cytolysin that mediates cytotoxicity, cytokine synthesis, inflammation and virulence. AB - Streptococcus agalactiae can cause urinary tract infection (UTI) including cystitis and asymptomatic bacteriuria (ABU). The early host-pathogen interactions that occur during S. agalactiae UTI and subsequent mechanisms of disease pathogenesis are poorly defined. Here, we define the early interactions between human bladder urothelial cells, monocyte-derived macrophages, and mouse bladder using uropathogenic S. agalactiae (UPSA) 807 and ABU-causing S. agalactiae (ABSA) 834 strains. UPSA 807 adhered, invaded and killed bladder urothelial cells more efficiently compared to ABSA 834 via mechanisms including low-level caspase-3 activation, and cytolysis, according to lactate dehydrogenase release measures and cell viability. Severe UPSA 807-induced cytotoxicity was mediated entirely by the bacterial beta-hemolysin/cytolysin (beta-H/C) because an beta-H/C-deficient UPSA 807 isogenic mutant, UPSA 807DeltacylE, was not cytotoxic in vitro; the mutant was also significantly attenuated for colonization in the bladder in vivo. Analysis of infection-induced cytokines, including IL-8, IL-1beta, IL-6 and TNF alpha in vitro and in vivo revealed that cytokine and chemokine responses were dependent on expression of beta-H/C that also elicited severe bladder neutrophilia. Thus, virulence of UPSA 807 encompasses adhesion to, invasion of and killing of bladder cells, pro-inflammatory cytokine/chemokine responses that elicit neutrophil infiltration, and beta-H/C-mediated subversion of innate immune mediated bacterial clearance from the bladder. PMID- 27383372 TI - Modeling Microvirus Capsid Protein Evolution Utilizing Metagenomic Sequence Data. AB - The Microviridae are increasingly becoming recognized as one of the most globally ubiquitous and highly diverse virus families, and as such, provide an advantageous model for studying virus evolution and adaptation. Here, we utilize microvirus sequences from diverse physiochemical environments, including novel sequences from a high-temperature acidic lake, to chart the outcome of natural selection in the main structural protein of the virus. Each icosahedral microvirus virion is composed of sixty identical capsid proteins that interact along twofold, threefold and fivefold symmetry axis interfaces to encapsidate a small, circular, single-stranded DNA genome. Viable assembly of the virus is guided by scaffolding proteins, which coordinate inter-subunit contacts between the capsid proteins. Structure-based analysis indicates that amino acid sequence conservation is predominantly localized to the twofold axis interface. While preservation of this quaternary interface appears to be essential, tertiary and secondary structural features of the capsid protein are permissive to considerable sequence variation. PMID- 27383374 TI - Operando Synchrotron X-ray Powder Diffraction and Modulated-Excitation Infrared Spectroscopy Elucidate the CO2 Promotion on a Commercial Methanol Synthesis Catalyst. AB - Optimal amounts of CO2 are added to syngas to boost the methanol synthesis rate on Cu-ZnO-Al2 O3 in the industrial process. The reason for CO2 promotion is not sufficiently understood at the particle level due to the catalyst complexity and the high demands of characterization under true reaction conditions. Herein, we applied operando synchrotron X-ray powder diffraction and modulated-excitation infrared spectroscopy on a commercial catalyst to gain insights into its morphology and surface chemistry. These studies unveiled that Cu and ZnO agglomerate and ZnO particles flatten under CO/H2 and/or CO2 /H2 . Under the optimal CO/CO2 /H2 mixture, sintering is prevented and ZnO crystals adopt an elongated shape due to the minimal presence of the H2 O byproduct, enhancing the water-gas shift activity and thus the methanol production. Our results provide a rationale to the CO2 promotion emphasizing the importance of advanced analytical methods to establish structure-performance relations in heterogeneous catalysis. PMID- 27383373 TI - Self-Sealing Porous Silicon-Calcium Silicate Core-Shell Nanoparticles for Targeted siRNA Delivery to the Injured Brain. AB - Calcium ions react with silicic acid released from dissolving porous silicon nanoparticles to create an insoluble calcium silicate shell. The calcium silicate shell traps and protects an siRNA payload, which can be delivered to neuronal tissues in vitro or in vivo. Gene delivery is enhanced by the action of targeting and cell-penetrating peptides attached to the calcium silicate shell. PMID- 27383375 TI - Curing characteristics of flowable and sculptable bulk-fill composites. AB - OBJECTIVES: The aim of this study was to determine and correlate the degree of conversion (DC) with Vickers hardness (VH) and translucency parameter (TP) with the depth of cure (DoC) of five bulk-fill composites. MATERIALS AND METHODS: Six specimens per group, consisting of Tetric EvoCeram Bulk Fill ("TEC Bulk," Ivoclar Vivadent), SonicFill (Kerr), SDR Smart Dentin Replacement ("SDR," Dentsply), Xenius base ("Xenius," StickTech; commercialized as EverX Posterior, GC), Filtek Bulk Fill flowable ("Filtek Bulk," 3M ESPE), and Tetric EvoCeram ("TEC," control), were prepared for DC and VH: two 2-mm-thick layers, each light-cured for 10 s; one 4-mm bulk-fill, light-cured for 10 or 20 s; and one 6-mm bulk-fill, cured for 20 s. DC was measured using a Fourier-transform infrared spectrometer, VH using a Vickers hardness tester. DoC and TP were measured using an acetone shaking test and a spectrophotometer, respectively. Data were analyzed using ANOVA and Pearson's correlation (alpha = 0.05). RESULTS: DC and VH ranged between 40-70 % and 30-80 VHN, respectively. TEC Bulk, Xenius, and SonicFill, bulk-filled as 4-mm-thick specimens, showed bottom-to-top hardness ratios above 80 % after 20 s curing. A positive linear correlation was found for bottom DC and VH. An average DC ratio of 0.9 corresponded to a bottom-to-top VH ratio of 0.8. CONCLUSIONS: Sculptable bulk-fills require 20 s, whereas 10 s curing time was sufficient for flowable bulk-fills using a high-intensity LED unit. CLINICAL RELEVANCE: Clinicians should be aware that longer curing times may be required for sculptable than flowable bulk-fill composites in order to achieve optimal curing characteristics. PMID- 27383376 TI - Bad things come easier to the mind but harder to the body: Evidence from brain oscillations. AB - An intriguing finding of research on emotional processing is a discrepancy between perception and behavior. Perceptually, a robust finding is that negative stimuli are processed faster and more efficiently than positive stimuli. Behaviorally, a similarly robust finding is that response times are slower for negative than for positive stimuli. We proposed and tested a novel account to explain this still unexplained discrepancy, on the basis of the assumption that negative valence narrows perceptual processes to the benefit of speeded perception, but broadens motor processes at the cost of slowed responding. Participants performed a valence judgment task in which they responded with their left or right hand to negative and positive stimuli that were presented on the left or right, and we measured the activation of relevant/deactivation of irrelevant perceptual and motor processes, as revealed by the lateralization of electroencephalographic brain oscillations. Stimulus-related lateralization of alpha activity (8-12 Hz) over perceptual areas was increased for negative stimuli, indicating more efficient perceptual processing. By contrast, response related lateralization of beta activity (20-25 Hz) over motor areas was decreased for negative stimuli, indicating less efficient response activation. Consistent with our predictions, more detailed analyses showed that both lateralization effects were caused by dynamics at the level of inhibiting irrelevant processes. For negative as compared to positive stimuli, the inhibition of irrelevant perceptual processes was increased, but the inhibition of irrelevant motor processes was decreased. These findings indicate that the discrepancy between perception and behavior in emotional processing may stem from asymmetrical effects of emotional valence on the breadth of cortical activations in perceptual and motor networks. PMID- 27383377 TI - Effects of mineralocorticoid receptor blockade on empathy in patients with major depressive disorder. AB - BACKGROUND: The mineralocorticoid receptor (MR) is highly expressed in the hippocampus and prefrontal cortex and is involved in social cognition. We recently found that pharmacological stimulation of the MR enhances emotional empathy but does not affect cognitive empathy. In the current study, we examined whether blockade of the MR impairs empathy in patients with major depressive disorder (MDD) and healthy individuals. METHODS: In a placebo-controlled study, we randomized 28 patients with MDD without psychotropic medication and 43 healthy individuals to either placebo or 300 mg spironolactone, a MR antagonist. Subsequently, all participants underwent two tests of social cognition, the Multifaceted Empathy Test (MET) and the Movie for the Assessment of Social Cognition (MASC), measuring cognitive and emotional facets of empathy. RESULTS: In the MET, we found no significant main effect of treatment or main effect of group for cognitive empathy but a highly significant treatment by group interaction (p < 0.01). Patients had higher cognitive empathy scores compared to controls in the placebo condition but not after spironolactone. Furthermore, in the spironolactone condition reduced cognitive empathy was seen in MDD patients but not in controls. Emotional empathy was not affected by MR blockade. In the MASC, no effect of spironolactone could be revealed. CONCLUSION: Depressed patients appear to exhibit greater cognitive empathy compared to healthy individuals. Blockade of MR reduced cognitive empathy in MDD patients to the level of healthy individuals. Future studies should further clarify the impact of MR functioning on different domains of social cognition in psychiatric patients. PMID- 27383379 TI - Interpersonal Emotion Regulation Among Adolescent Athletes: A Bayesian Multilevel Model Predicting Sport Enjoyment and Commitment. AB - Efforts to regulate emotions can influence others, and interpersonal emotion regulation within teams may affect athletes' own affective and motivational outcomes. We examined adolescent athletes' (N = 451, N teams = 38) self- and interpersonal emotion regulation, as well as associations with peer climate, sport enjoyment, and sport commitment within a multilevel model of emotion regulation in teams. Results of multilevel Bayesian structural equation modeling showed that athletes' self-worsening emotion regulation strategies were negatively associated with enjoyment while other-improving emotion regulation strategies were positively associated enjoyment and commitment. The team-level interpersonal emotion regulation climate and peer motivational climates were also associated with enjoyment and commitment. Team-level factors moderated some of the relationships between athletes' emotion regulation with enjoyment and commitment. These findings extend previous research by examining interpersonal emotion regulation within teams using a multilevel approach, and they demonstrate the importance of person- and team-level factors for athletes' enjoyment and commitment. PMID- 27383378 TI - Molecular basis of the remarkable species selectivity of an insecticidal sodium channel toxin from the African spider Augacephalus ezendami. AB - The inexorable decline in the armament of registered chemical insecticides has stimulated research into environmentally-friendly alternatives. Insecticidal spider-venom peptides are promising candidates for bioinsecticide development but it is challenging to find peptides that are specific for targeted pests. In the present study, we isolated an insecticidal peptide (Ae1a) from venom of the African spider Augacephalus ezendami (family Theraphosidae). Injection of Ae1a into sheep blowflies (Lucilia cuprina) induced rapid but reversible paralysis. In striking contrast, Ae1a was lethal to closely related fruit flies (Drosophila melanogaster) but induced no adverse effects in the recalcitrant lepidopteran pest Helicoverpa armigera. Electrophysiological experiments revealed that Ae1a potently inhibits the voltage-gated sodium channel BgNaV1 from the German cockroach Blattella germanica by shifting the threshold for channel activation to more depolarized potentials. In contrast, Ae1a failed to significantly affect sodium currents in dorsal unpaired median neurons from the American cockroach Periplaneta americana. We show that Ae1a interacts with the domain II voltage sensor and that sensitivity to the toxin is conferred by natural sequence variations in the S1-S2 loop of domain II. The phyletic specificity of Ae1a provides crucial information for development of sodium channel insecticides that target key insect pests without harming beneficial species. PMID- 27383380 TI - Association of living in a farming environment with asthma incidence in Canadian children. AB - OBJECTIVE: The objective of this population-based 14-year follow-up study was to examine the effect of living in a farm environment on asthma incidence in children. METHODS: A total of 10,941 children of ages 0 to 11 years who were free of asthma and wheeze at the baseline (1994-1995) in the National Longitudinal Survey of Children and Youth were considered in the study. Children's living environment was classified, based on interviewer's observation, into three categories: non-rural, rural non-farming, and farming. An incidence of asthma was obtained from health-professional diagnosed asthma reported either by the person most knowledgeable for children under 15 years or by the children themselves if they were of ages 16 years and over. RESULTS: The 14-year cumulative incidence of asthma among children living in farming environments was 10.18%, which was significantly lower than that observed for children living in rural non-farming (13.12%) and non-rural environments (16.50%). After adjusting for age group, number of older siblings, allergy, parental history of asthma, dwelling in need of repairs and SES index, a dose-response relationship was observed with children living in rural non-farming and farming environments having significantly reduced risk of asthma [hazard ratio (HR): 0.77; 95% confidence interval (CI): (0.60, 1.00); p = 0.047 and HR: 0.56; 95% CI: (0.41,0.77); p < 0.001] in comparison to those living in non-rural environments. CONCLUSION: This cohort study provides further evidence that living in a farming environment during childhood is protective of asthma incidence in adolescence and adulthood and this finding provides further support for the hygiene hypothesis. PMID- 27383381 TI - Perfusion-Derived Dynamic 4D CT Angiography Identifies Carotid Pseudo-Occlusion in Hyperacute Stroke. AB - BACKGROUND: Differentiation between true acute tandem occlusion involving the extracranial internal carotid artery (ICA) from pseudotandem occlusion with a patent extracranial ICA has important prognostic and therapeutic implications. We explored the utility of perfusion-derived 4-dimensional CT angiogram (4D-CTA) in identifying carotid pseudo-occlusion in a single-center pilot study. METHODS: Acute stroke patients with delayed antegrade ICA flow on 4D-CTA despite an apparent tandem occlusion on conventional single-phase CTA were prospectively identified over a 2.5-year period (2013-2015). RESULTS: Eight patients were identified. Delayed antegrade intracranial flow from the apparently occluded ICA was detected up to 50 seconds after contrast administration on 4D-CTA. The distal intracranial ICA was the most common site of true occlusion. Reconstruction of the 4D-CTA images required an additional processing time of 2-3 minutes. CONCLUSIONS: 4D-CTA is a novel noninvasive technique that can identify carotid pseudo-occlusion in the acute stroke setting. Our preliminary findings suggest that 4D-CTA can be easily incorporated into an existing acute stroke neuroimaging protocol. PMID- 27383382 TI - Congenital Cataract, Nasolacrimal Duct Obstruction, and Methicillin-Resistant Staphylococcus aureus Conjunctivitis: When to Operate? AB - Methicillin-resistant Staphylococcus aureus is one of the toughest organisms to treat, especially in cases where intraocular surgery is contemplated, because the risks are aggravated. Conjunctival swab culture and sensitivity tests are significant when there is history of recent hospitalization. In this report, an infant with successful cataract surgery after elimination of the organism is presented. PMID- 27383383 TI - Orbital Imaging to Identify a "Lost" Lateral Rectus Muscle. AB - A 36-year-old man presented with a large-angle esotropia and limited abduction of the right eye. A computed tomography scan of his orbits showed an absent lateral rectus muscle. At the time of surgery, a normal-appearing lateral rectus muscle was found. Postoperative magnetic resonance imaging showed a present but atrophic lateral rectus muscle. PMID- 27383384 TI - Departments of Surgery and Mentorship. PMID- 27383385 TI - Sexual Orientation Identity in Relation to Minority Stress and Mental Health in Sexual Minority Women. AB - PURPOSE: Research often erases the distinct experiences of bisexual and queer women through collapsing participants with lesbian or gay women. In addition, queer is often not included as a sexual orientation identity in research, therefore limiting the available information about how this group experiences minority stress. Given these limitations, we sought to compare groups, based on their sexual orientation identity, on experiences of minority stress and mental health to further understand between group differences that often go unaccounted for in research. METHODS: Participants (N = 249; age range 19-77; M = 38.43, SD = 12.98) completed an online survey exploring experiences of minority stress and mental health. RESULTS: We found that the group most at risk for encountering minority stressors depended on the specific stressor being examined. Queer and gay or lesbian women encountered greater victimization, discrimination, and expectations of discrimination than bisexual women. However, bisexual women had higher levels of identity concealment and internalized heterosexism than gay, lesbian, or queer women. While queer women tended to have fewer proximal stressors, they were similar to bisexual women in terms of psychological distress, with both groups scoring higher than gay or lesbian women. CONCLUSIONS: These results highlight the need to examine between group differences in future research. The experiences of minority stress appear to complexly relate to psychological distress in varying ways for different groups of women, with bisexual and queer women having the highest rates of psychological distress although they vary in the types of stressors that they encounter. In addition, the experiences of queer women were divergent from those of gay, lesbian, or bisexual women across many of the stressors, indicating that there is a need to further recognize this distinct group of women in future research. PMID- 27383386 TI - Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1. AB - We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs), cellular hypoxia increased after incubation with high glucose (HG). A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD) overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1), a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner. PMID- 27383387 TI - Structural Signature of Plasticity Unveiled by Nano-Scale Viscoelastic Contact in a Metallic Glass. AB - Room-temperature plasticity in metallic glasses (MGs) is commonly associated with local structural heterogeneity; however, direct observation of the subtle structural change caused by plasticity is vitally important but the data are extremely scarce. Based on dynamic atomic force microscopy (DAFM), here we show that plasticity-induced structural evolution in a Zr-Ni MG can be revealed via nano-scale viscoelastic contacts between an AFM tip and plastically deformed MG surface layers. Our experimental results clearly show a spatial amplification of the nano-scale structural heterogeneity caused by the distributed plastic flow, which can be linked to the limited growth, reorientation and agglomeration of some nano-scale energy-absorbing regions, which are reminiscent of the behavior of the defect-like regions with non-affine deformation as conceived in many theories and models. Furthermore, we are able to experimentally extract the thermodynamic properties of these nano-scale regions, which possess an energy barrier of 0.3-0.5 eV, about half of that for a typical shear transformation event that usually occurs at the onset of plasticity. The outcome of our current work sheds quantitative insights into the correlation between plasticity and structural heterogeneity in MGs. PMID- 27383388 TI - Searching for a neurologic injury's Wechsler Adult Intelligence Scale-Third Edition profile. AB - This study aimed to investigate the presence of a Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) cognitive profile in a Portuguese neurologic injured sample. The Portuguese WAIS-III was administered to 81 mixed neurologic patients and 81 healthy matched controls selected from the Portuguese standardization sample. Although the mixed neurologic injury group performed significantly lower than the healthy controls for the majority of the WAIS-III scores (i.e., composite measures, discrepancies, and subtests), the mean scores were within the normal range and, therefore, at risk of being unobserved in a clinical evaluation. ROC curves analysis showed poor to acceptable diagnostic accuracy for the WAIS-III composite measures and subtests (Working Memory Index and Digit Span revealed the highest accuracy for discriminating between participants, respectively). Multiple regression analysis showed that both literacy and the presence of brain injury were significant predictors for all of the composite measures. In addition, multiple regression analysis also showed that literacy, age of injury onset, and years of survival predicted all seven composite measures for the mixed neurologic injured group. Despite the failure to find a WAIS-III cognitive profile for mixed neurologic patients, the results showed a significant influence of brain lesion and literacy in the performance of the WAIS-III. PMID- 27383390 TI - Comment on Comparison of the Total Phenolic and Ascorbic Acid Content of Freeze Dried and Air-Dried Marionberry, Strawberry, and Corn Grown Using Conventional, Organic, and Sustainable Agricultural Practices. PMID- 27383389 TI - Guided and Unguided Internet-Based Treatment for Problematic Alcohol Use - A Randomized Controlled Pilot Trial. AB - BACKGROUND: The Internet has increasingly been studied as mode of delivery for interventions targeting problematic alcohol use. Most interventions have been fully automated, but some research suggests that adding counselor guidance may improve alcohol consumption outcomes. METHODS: An eight-module Internet-based self-help program based on cognitive behavioral therapy (CBT) was tested among Internet help-seekers. Eighty participants with problematic alcohol use according to the Alcohol Use Disorders Identification Test (AUDIT; scores of >= 6 for women and >= 8 for men) were recruited online from an open access website and randomized into three different groups. All groups were offered the same self help program, but participants in two of the three groups received Internet-based counselor guidance in addition to the self-help program. One of the guidance groups was given a choice between guidance via asynchronous text messages or synchronous text-based chat, while the other guidance group received counselor guidance via asynchronous text messages only. RESULTS: In the choice group, 65% (13 of 20 participants) chose guidance via asynchronous text messages. At the 10 week post-treatment follow-up, an intention-to-treat (ITT) analysis showed that participants in the two guidance groups (choice and messages) reported significantly lower past week alcohol consumption compared to the group without guidance; 10.8 (SD = 12.1) versus 22.6 (SD = 18.4); p = 0.001; Cohen's d = 0.77. Participants in both guidance groups reported significantly lower scores on the AUDIT at follow-up compared to the group without guidance, with a mean score of 14.4 (SD = 5.2) versus 18.2 (SD = 5.9); p = 0.003; Cohen's d = 0.68. A higher proportion of participants in the guidance groups said that they would recommend the program compared to the group without guidance (81% for choice; 93% for messages versus 47% for self-help). CONCLUSION: Self-help programs for problematic alcohol use can be more effective in reducing alcohol consumption over a 10-week period when counselor guidance is added. TRIAL REGISTRATION: Clinicaltrials.gov NCT02384304. PMID- 27383391 TI - A new plasmid-based microRNA inhibitor system that inhibits microRNA families in transgenic mice and cells: a potential new therapeutic reagent. PMID- 27383392 TI - ISSY32 Highlights. PMID- 27383393 TI - Eccentricity Effects on the Efficiency of Attentional Networks: Evidence From a Modified Attention Network Test. AB - The effects of eccentricity on the attentional modulation of visual discrimination have been widely studied; however, the substrate of this complex phenomenon is poorly understood. Here, we provided a measure of the effects of eccentricity on three attentional networks: alerting, orienting, and executive attention. Participants (N = 63) were tested with a modified attention network test that included an additional eccentricity variation; this test allowed us to investigate the efficiency of the attentional networks at near and far eccentricities. Compared with targets at the near eccentricity, targets at the far eccentricity generally elicited significantly longer reaction times. We also found the far eccentricity was associated with smaller orienting effect scores and larger executive control scores than the near eccentricity. Interestingly, at the near eccentricity, executive control scores were larger when the spatial information was neutral (no cue, center cue, and double cue), but at the far eccentricity, the scores were larger when the spatial information was valid (spatial cue). We propose that the allocation of attentional resources differed among these cue conditions and influenced the interference caused by conflicting information. PMID- 27383394 TI - The Interaction Between Vision and Eye Movements. AB - The existence of a central fovea, the small retinal region with high analytical performance, is arguably the most prominent design feature of the primate visual system. This centralization comes along with the corresponding capability to move the eyes to reposition the fovea continuously. Past research on visual perception was mainly concerned with foveal vision while the observers kept their eyes stationary. Research on the role of eye movements in visual perception emphasized their negative aspects, for example, the active suppression of vision before and during the execution of saccades. But is the only benefit of our precise eye movement system to provide high acuity of the small foveal region, at the cost of retinal blur during their execution? In this review, I will compare human visual perception with and without saccadic and smooth pursuit eye movements to emphasize different aspects and functions of eye movements. I will show that the interaction between eye movements and visual perception is optimized for the active sampling of information across the visual field and for the calibration of different parts of the visual field. The movements of our eyes and visual information uptake are intricately intertwined. The two processes interact to enable an optimal perception of the world, one that we cannot fully grasp by doing experiments where observers are fixating a small spot on a display. PMID- 27383395 TI - Application of Machine Learning to Arterial Spin Labeling in Mild Cognitive Impairment and Alzheimer Disease. AB - Purpose To investigate whether multivariate pattern recognition analysis of arterial spin labeling (ASL) perfusion maps can be used for classification and single-subject prediction of patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) and subjects with subjective cognitive decline (SCD) after using the W score method to remove confounding effects of sex and age. Materials and Methods Pseudocontinuous 3.0-T ASL images were acquired in 100 patients with probable AD; 60 patients with MCI, of whom 12 remained stable, 12 were converted to a diagnosis of AD, and 36 had no follow-up; 100 subjects with SCD; and 26 healthy control subjects. The AD, MCI, and SCD groups were divided into a sex- and age-matched training set (n = 130) and an independent prediction set (n = 130). Standardized perfusion scores adjusted for age and sex (W scores) were computed per voxel for each participant. Training of a support vector machine classifier was performed with diagnostic status and perfusion maps. Discrimination maps were extracted and used for single-subject classification in the prediction set. Prediction performance was assessed with receiver operating characteristic (ROC) analysis to generate an area under the ROC curve (AUC) and sensitivity and specificity distribution. Results Single-subject diagnosis in the prediction set by using the discrimination maps yielded excellent performance for AD versus SCD (AUC, 0.96; P < .01), good performance for AD versus MCI (AUC, 0.89; P < .01), and poor performance for MCI versus SCD (AUC, 0.63; P = .06). Application of the AD versus SCD discrimination map for prediction of MCI subgroups resulted in good performance for patients with MCI diagnosis converted to AD versus subjects with SCD (AUC, 0.84; P < .01) and fair performance for patients with MCI diagnosis converted to AD versus those with stable MCI (AUC, 0.71; P > .05). Conclusion With automated methods, age- and sex-adjusted ASL perfusion maps can be used to classify and predict diagnosis of AD, conversion of MCI to AD, stable MCI, and SCD with good to excellent accuracy and AUC values. (c) RSNA, 2016. PMID- 27383396 TI - Human Blood Autoantibodies in the Detection of Colorectal Cancer. AB - Colorectal cancer (CRC) is the second most common malignancy in the western world. Early detection and diagnosis of all cancer types is vital to improved prognosis by enabling early treatment when tumours should be both resectable and curable. Sera from 3 different cohorts; 42 sera (21 CRC and 21 matched controls) from New York, USA, 200 sera from Pittsburgh, USA (100 CRC and 100 controls) and 20 sera from Dundee, UK (10 CRC and 10 controls) were tested against a panel of multiple tumour-associated antigens (TAAs) using an optimised multiplex microarray system. TAA specific IgG responses were interpolated against the internal IgG standard curve for each sample. Individual TAA specific responses were examined in each cohort to determine cutoffs for a robust initial scoring method to establish sensitivity and specificity. Sensitivity and specificity of combinations of TAAs provided good discrimination between cancer-positive and normal serum. The overall sensitivity and specificity of the sample sets tested against a panel of 32 TAAs were 61.1% and 80.9% respectively for 6 antigens; p53, AFP, K RAS, Annexin, RAF1 and NY-CO16. Furthermore, the observed sensitivity in Pittsburgh sample set in different clinical stages of CRC; stage I (n = 19), stage II (n = 40), stage III (n = 34) and stage IV (n = 6) was similar (73.6%, 75.0%, 73.5% and 83.3%, respectively), with similar levels of sensitivity for right and left sided CRC. We identified an antigen panel of sufficient sensitivity and specificity for early detection of CRC, based upon serum profiling of autoantibody response using a robust multiplex antigen microarray technology. This opens the possibility of a blood test for screening and detection of early colorectal cancer. However this panel will require further validation studies before they can be proposed for clinical practice. PMID- 27383397 TI - Lanthanide Hydroxide Nanoparticles Induce Angiogenesis via ROS-Sensitive Signaling. AB - Recent studies suggest that the nanorods consisting of europium hydroxide could promote angiogenesis. In this study, it is sought to determine if additional types of nanoparticles are capable of enhancing angiogenesis and in addition, understand the underlying mechanisms. For this reason, a method is employed that combines a high throughput in vitro cell based screen coupled with an in vivo validation using vascular specific green fluorescent protein reporter transgenic zebrafish for examining proangiogenesis activity. After screening multiple types of nanoparticles, it is discovered that four of them, Eu(III) (OH)3 rods (Eu rods), Eu(III) (OH)3 spheres (Eu spheres), Tb(III) (OH)3 rods (Tb rods), and Tb(III) (OH)3 spheres (Tb spheres), are the most effective in promoting angiogenesis. It is also showed that ionic forms of europium nitrate [Eu(NO3 )3 ] (Eu) and terbium nitrate [Tb(NO3 )3 ] (Tb), the two lanthanide elements for these four nanoparticles, are also capable of enhancing angiogenesis. However, this effect is further enhanced by nanoparticle synthesis. Finally, it is demonstrated that reactive oxygen species H2 O2 is a key factor in the process of proangiogenesis by lanthanide elemental nanoparticles. PMID- 27383398 TI - Rectal cancers with microscopic circumferential resection margin involvement (R1 resections): Survivals, patterns of recurrence, and prognostic factors. AB - BACKGROUND AND OBJECTIVES: We have reviewed our series of rectal cancer patients with circumferential resection margin involvement (R1) with particular regard to survival and prognostic factors. METHODS: R1 rectal cancer patients undergoing surgery at the Leicester Royal Infirmary between 1998 and 2008. Age, gender, radiological, and pathological tumor characteristics, neoadjuvant and adjuvant therapies were examined as prognostic factors on the overall survival (OS) and disease-free survival (DFS) at 5-year follow-up. RESULTS: A total of 885 rectal cancers were reviewed. Six hundred ninety-nine patients underwent a mesorectal excision and 71 of them were R1 resections (12.9%). OS was 43.7% (CI95% 33.5 53.8%; median survival 39 months). DFS was 57.4% (CI95% 43.0-71.8%; median survival 31 months). Pelvic recurrence rate occurred in 16 patients (26.2%, CI95% 16.5-36.0%), systemic recurrence rate in 23 patients (37.7%, CI95% 25.5-49.9%). At Cox-regression LNR and adjuvant chemotherapy were associated with both OS and DFS. No significant association was found between OS or DFS and adjuvant radiotherapy. CONCLUSIONS: In our series of R1 patients, the rates of local recurrence and OS at 5 years were 26.2% and 43.7%, respectively. Factors influencing systemic recurrences (LNR, adjuvant chemotherapy) are more associated with OS and DFS than those potentially affecting locoregional recurrences (adjuvant radiotherapy). J. Surg. Oncol. 2016;114:642-648. (c) 2016 Wiley Periodicals, Inc. PMID- 27383399 TI - Cloning and characterization of three ketoreductases from soil metagenome for preparing optically active alcohols. AB - OBJECTIVES: To discover novel ketoreductases (KRED) from soil metagenome preparation of chiral alcohols. RESULTS: Three putative KRED were cloned, heterologously expressed in Eschericha coli and characterized based on the sequence analysis of soil metagenome. All the three enzymes (KRED424, KRED432, and KRED433) had maximum activity at 55 degrees C and pH 7. KRED424 had a broader substrate spectrum compared with the other two. Three prochiral carbonyl compounds were used to evaluate the abilities of enantioselective reductions of the KRED. For N-Boc-3-pyrrolidone, all enzymes produced an (S)-type alcohol in enantiomeric excess (>99 % ee). For ethyl 2-oxo-4-phenylbutyrate, KRED424 showed a higher conversion (91.5 %) and enantioselectivity (S-type, >99 % ee) than KRED432 and KRED433. For ethyl 4-chloroacetoacetate (COBE), both of KRED424 and KRED433 completely converted 20 mM substrate and KRED433 could obtain an (R) alcohol with 94 % ee. CONCLUSIONS: The three ketoreductases have potential in the preparation of pharmaceuticals and fine chemicals. PMID- 27383400 TI - Advances in the management of chronic insomnia. AB - Chronic insomnia is a common condition that affects people worldwide and has negative effects on patients' health and wellbeing. The treatment of insomnia can be complex and time consuming for patients and providers. Although behavioral interventions are the first line therapy, there are barriers to access for these treatments. However, in recent years, alternative ways of providing these behavioral therapies that make them more widely available have been investigated. Drugs also play an important role in the treatment of insomnia and new drugs have been introduced as options for treating patients with sleep initiation and sleep maintenance insomnia. In this review, we will discuss advances in the past six years in both non-pharmacologic and pharmacologic treatments for patients with chronic insomnia. We will also review the controversies surrounding some of the current drug treatments, as well as the role that technology and personal activity monitoring devices may play in treating insomnia. PMID- 27383401 TI - Sheila Hollins: Looking beyond learning disabilities. PMID- 27383403 TI - Development and Assessment of an Advanced Pediatric Airway Management Curriculum With Integrated Intubation Videos. AB - OBJECTIVES: Opportunities to learn advanced airway management skills on pediatric patients in the emergency department are limited. Current strategies have focused largely on traditional didactics coupled with procedural skills training using simulation. However, these approaches are limited in their exposure to anatomic variation and realism. Here, we describe the development and assessment of an advanced airway curriculum that integrates videolaryngoscopic recordings obtained during actual patient intubations into a series of interactive educational sessions. METHODS: Trainees and attending physicians were surveyed anonymously to assess the impact of participation in the curriculum. A mixed methods approach to statistical analysis was used. Rating questions were used to evaluate the relative impact of this approach over other traditional strategies and recurrent themes within open-ended questions were identified. RESULTS: Participants reported this to be a highly effective means of learning about pediatric laryngoscopy and endotracheal intubation and regarded it more highly than other traditional educational approaches. Identified benefits included repetitive exposure, approaches to laryngoscopy, the realism of teaching using real and varied anatomy, and the opportunities to identify and troubleshoot difficulty in a learning environment. CONCLUSIONS: An advanced pediatric airway curriculum that integrates intubation videos obtained during videolaryngoscopy was highly regarded by pediatric emergency medicine providers. Content emphasis can be shifted to meet the needs of pediatric emergency medicine providers with all levels of skill and experience. PMID- 27383402 TI - The presence of bacteria within tissue provides insights into the pathogenesis of oral lichen planus. AB - Oral lichen planus (OLP) is a chronic T cell-mediated mucocutaneous disease of unknown etiopathogenesis. Although various antigens have been considered, what actually triggers the inflammatory response of T cells is unknown. In the present study, we propose that intracellular bacteria present within tissues trigger T cell infiltration and provide target antigens. Sections of OLP (n = 36) and normal (n = 10) oral mucosal tissues were subjected to in situ hybridization using a universal probe targeting the bacterial 16S rRNA gene and immunohistochemistry with anti-CD3, anti-CD4, anti-CD8, and anti-macrophage specific antibodies. Bacteria were abundant throughout the epithelium and the lamina propria of OLP tissues, which exhibited positive correlations with the levels of infiltrated CD3(+), CD4(+), and CD8(+) cells. Furthermore, bacteria were detected within the infiltrated T cells. Pyrosequencing analysis of the mucosal microbiota from OLP patients (n = 13) and control subjects (n = 11) revealed a decrease in Streptococcus and increases in gingivitis/periodontitis associated bacteria in OLP lesions. Using the selected bacterial species, we demonstrated that certain oral bacteria damage the epithelial physical barrier, are internalized into epithelial cells or T cells, and induce production of T cell chemokines CXCL10 and CCL5. Our findings provide insights into the pathogenesis of OLP. PMID- 27383404 TI - A Large Case Series of Acute Pediatric Methotrexate Ingestions: Significant Clinical Effects Are Rare. AB - OBJECTIVE: Significant adverse effects after acute pediatric methotrexate (MTX) exposures have been limited to parenteral exposures. Treatment recommendations for pediatric MTX exposures do not differentiate between routes of exposure. We report the incidence of significant clinical effects and drug-specific treatments reported in a large series of acute, pediatric MTX ingestions. METHODS: Poison center records of all MTX ingestions by patients younger than 17 years during 2000 to 2005 were collected from 6 poison centers. The cases included all MTX ingestions including those with additional substances. One trained reviewer, blinded to the study purpose, used a standardized data collection form to extract study data. Missing or conflicting data were reconciled with predetermined process. RESULTS: Forty-seven cases were documented for 6 years, 42 (89%) of which were unintentional. Thirty-six percent (17/47) were male. The mean age for the unintentional ingestions was 3.7 years (range, 20 days-17 y; median, 2 y). Five cases (11%) were intentional suicidal ingestions in teenagers. The mean dose in acute, unintentional ingestions (AUIs) in all children and in children younger than 6 years was the same, 8 mg (range, 2.5-17.5 mg). Eleven patients (23%) had follow-up greater than 12 hours. No patient with an AUI developed MTX-induced sedation, hepatotoxicity, renal insufficiency, seizures, or bone marrow suppression. Three patients with an AUI received folinic acid, but no patients in this group received sodium bicarbonate or hemodialysis. One patient with an intentional suicidal exposure developed hepatotoxicity, but the patient also ingested a toxic dose of acetaminophen and valproate. Hemodialysis was performed once on this patient. No patient died. CONCLUSIONS: Acute pediatric MTX ingestion is uncommon. Methotrexate-induced seizure, renal failure, hepatic injury, and sedation were not documented in our series. Supportive care and observation only should be considered the mainstay of treatment of pediatric AUIs. Prospective verification of our findings is warranted. PMID- 27383405 TI - Elevated Baseline Cortisol Levels Are Predictive of Bad Outcomes in Critically Ill Children. AB - OBJECTIVE: The definition of an adequate adrenal response in critically ill children continues to be controversial. We aimed to evaluate the cortisol levels at baseline and after adrenocorticotropin (ACTH) stimulation and determine their association to clinical outcome of critically ill children. METHODS: All children who underwent an ACTH test in the pediatric intensive care unit (PICU) in a tertiary medical center between 2006 and 2013 were included in the study. Data on age, sex, diagnosis, vasoactive-inotropic score, length of pediatric intensive care unit stay, and mortality were obtained. Laboratory variables included hematologic and chemistry data, arterial lactate, and total plasma cortisol levels at baseline and after ACTH stimulation. RESULTS: Ninety-nine patients (61 males; median [range] age, 2 [0-204] months) were enrolled. The mortality rate of children with a baseline cortisol level of 600 nmol/L or greater was 36% (12/33 patients) versus 18% (12/66 patients) for children with a baseline cortisol level of less than 600 nmol/L (odds ratio, 2.6 [95% confidence interval, 1-6.6]; P = 0.05). There was a positive correlation between baseline cortisol and lactate levels (r = 0.40, P < 0.0001), vasoactive-inotropic scores (r = 0.24, P = 0.02), and mortality (P = 0.05). There was no correlation between peak cortisol measured at the ACTH test or the delta increment of cortisol from baseline and mortality. CONCLUSIONS: A high baseline cortisol level in critically ill children was associated with more severe illness, higher lactate level, and a higher mortality rate. Routine baseline cortisol assessment is recommended to identify patients at high mortality risk. PMID- 27383406 TI - A Cross-Sectional Study of Emergency Department Visits by Children After All Terrain Vehicle Crashes, Motor Vehicle Crashes, and Sports Activities. AB - OBJECTIVES: All-terrain vehicle (ATV) crashes have been responsible for significant injuries among children, despite public education efforts. Our study examined pediatric ATV injury patterns in US emergency departments (EDs) compared with injuries after motor vehicle crash (MVC) and sports activities. METHODS: We studied 2006 to 2011 data from the Nationwide Emergency Department Sample. Children younger than 18 years and involved in ATV crashes, MVC, or sports activities were included. The primary outcome analyzed was a constructed binary measure identifying severe trauma, defined as injury severity score greater than 15. Logistic regression models were fit to determine the association between mechanism of injury and severe trauma. RESULTS: A total of 6,004,953 ED visits were identified. Of these, ATV crashes accounted for 3.4%, MVC accounted for 44.7%, and sports activities accounted for 51.9%. Emergency department visits after ATV crashes were more likely to result in admission (8%) and incur higher median charges ($1263) compared with visits after sports activities (1%, $1013). Visits after sports activities were 90% less likely to result in severe trauma when compared with ATV crash visits. Emergency department visits after ATV crashes result in severe injuries similar to those sustained in MVC (odds ratio, 1.03; P = 0.626). CONCLUSIONS: Pediatric ED visits after ATV crashes result in significant injuries and charges. Public health interventions such as education, legislation, and engineering are needed to reduce injuries among children and the subsequent ED visits for care. The impact of proven interventions may be greatest for children living in rural areas and among older children, 10 to 17 years old. PMID- 27383408 TI - Silicon Nanowire Sensors Enable Diagnosis of Patients via Exhaled Breath. AB - Two of the biggest challenges in medicine today are the need to detect diseases in a noninvasive manner and to differentiate between patients using a single diagnostic tool. The current study targets these two challenges by developing a molecularly modified silicon nanowire field effect transistor (SiNW FET) and showing its use in the detection and classification of many disease breathprints (lung cancer, gastric cancer, asthma, and chronic obstructive pulmonary disease). The fabricated SiNW FETs are characterized and optimized based on a training set that correlate their sensitivity and selectivity toward volatile organic compounds (VOCs) linked with the various disease breathprints. The best sensors obtained in the training set are then examined under real-world clinical conditions, using breath samples from 374 subjects. Analysis of the clinical samples show that the optimized SiNW FETs can detect and discriminate between almost all binary comparisons of the diseases under examination with >80% accuracy. Overall, this approach has the potential to support detection of many diseases in a direct harmless way, which can reassure patients and prevent numerous unpleasant investigations. PMID- 27383407 TI - Plasma cell maturity as a predictor of prognosis in multiple myeloma. AB - In this study, the impact of plasma cell maturity on the prognoses of multiple myeloma (MM) patients in the era of novel agents was investigated. Myeloma cell maturity was classified via immunophenotyping: myeloma cells showing mature plasma cell 1 (MPC-1)-positive and CD49e-positive cells were considered mature type; MPC-1-positive and CD49e-negative cells were considered intermediate type; and MPC-1-negative cells were considered immature type. This study included 87 newly diagnosed MM patients who were initially treated with bortezomib and/or chemotherapy. Myeloma cell maturity was a critical factor affecting overall survival (OS) in the cohort, with median OS not reached in mature-type, 50 months in intermediate-type, and 20 months in immature-type cells. Multivariate analysis showed that immature type and stage III according to the International Staging System were both independent prognostic factors affecting OS. The findings of this study demonstrate the clinical importance of myeloma cell classification according to immunophenotyping using MPC-1 and CD49e antibodies to determine patient prognosis in this era of novel therapeutic agents. PMID- 27383409 TI - Accuracy of Intraoral Digital Impressions for Whole Upper Jaws, Including Full Dentitions and Palatal Soft Tissues. AB - Intraoral digital impressions have been stated to meet the clinical requirements for some teeth-supported restorations, though fewer evidences were proposed for larger scanning range. The aim of this study was to compare the accuracy (trueness and precision) of intraoral digital impressions for whole upper jaws, including the full dentitions and palatal soft tissues, as well as to determine the effect of different palatal vault height or arch width on accuracy of intraoral digital impressions. Thirty-two volunteers were divided into three groups according to the palatal vault height or arch width. Each volunteer received three scans with TRIOS intraoral scanner and one conventional impression of whole upper jaw. Three-dimensional (3D) images digitized from conventional gypsum casts by a laboratory scanner were chose as the reference models. All datasets were imported to a specific software program for 3D analysis by "best fit alignment" and "3D compare" process. Color-coded deviation maps showed qualitative visualization of the deviations. For the digital impressions for palatal soft tissues, trueness was (130.54+/-33.95)MUm and precision was (55.26+/ 11.21)MUm. For the digital impressions for upper full dentitions, trueness was (80.01+/-17.78)MUm and precision was (59.52+/-11.29)MUm. Larger deviations were found between intraoral digital impressions and conventional impressions in the areas of palatal soft tissues than that in the areas of full dentitions (p<0.001). Precision of digital impressions for palatal soft tissues was slightly better than that for full dentitions (p = 0.049). There was no significant effect of palatal vault height on accuracy of digital impressions for palatal soft tissues (p>0.05), but arch width was found to have a significant effect on precision of intraoral digital impressions for full dentitions (p = 0.016). A linear correlation was found between arch width and precision of digital impressions for whole upper jaws (r = 0.326, p = 0.034 for palatal soft tissues and r = 0.485, p = 0.002 for full dentitions). It was feasible to use the intraoral scanner to obtain digital impressions for whole upper jaws. Wider dental arch contributed to lower precision of an intraoral digital impression. It should be confirmed in further studies that whether accuracy of digital impressions for whole upper jaws is clinically acceptable. PMID- 27383410 TI - Characterization of impurities of HIV NNRTI Doravirine by UHPLC-high resolution MS and tandem MS analysis. AB - World Health Organization estimates that 34 million individuals globally are living with Human Immunodeficiency Virus (HIV). Doravirine is a non-nucleoside reverse transcriptase inhibitors (NNRTI) being evaluated by Merck for the treatment of HIV-1 infection. Drug regulation authorities require the purity of a pharmaceutical to be fully defined. This is important to ensure that the pharmacological and toxicological effects are truly those of the drug substances and not because of the impurities. Thus, understanding the drug impurity profiles is critical to the safety and potency assessment of the drug candidate for clinical trials. The impurity characterization can also provide useful information for critical assessment of pharmaceutical processes. Advances in mass spectrometry instrumentation and methods allow the identification of impurities in pharmaceuticals with a minimum of sample material and increased sensitivity. In this study, a rapid and sensitive method was developed for the structural determination of the major impurities of doravirine. The study utilizes ultra performance liquid chromatography-high-resolution-tandem mass spectrometry (UHPLC HRMS/MS) techniques to perform structure elucidation of the unknown structures. This approach has significant impact on impurity structural elucidation, and a total of five trace-level impurities of doravirine were characterized using the developed method. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27383412 TI - Preface. PMID- 27383411 TI - Independent Tumor Origin in Two Cases of Synchronous Bilateral Clear Cell Renal Cell Carcinoma. AB - Bilateral renal cell carcinomas (RCCs) pose a challenge for clinical treatment and management. Most bilateral RCCs are sporadic, and do not show a hereditary pattern indicative of VHL syndrome or other inherited cancers. The origin and evolution of these sporadic bilateral RCCs remains elusive. We obtained normal and tumor samples from two male patients suffering from early stage synchronous bilateral clear cell RCC (ccRCC), and analyzed genomic DNA using whole exome sequencing and bisulfite pyrosequencing. We detected distinct 3p loss of heterozygosity (LOH) in both tumors in each patient. Two tumors within the same patient harbored distinct driver mutations and different CpG hypermethylation sites in the VHL promoter. Moreover, tumors exhibit independent evolutionary trajectories. Therefore, distinct 3p LOH, combined with contingent driver gene mutations and independent VHL hypermethylation, led to independent tumor origin and parallel evolution of bilateral ccRCC in these two patients. Our results indicate that tumors in these two cases were not due to common germline oncogenic mutations. They were results of multiple de novo mutations in each kidney, rather than primary ccRCC with contralateral renal metastasis. Therefore, histopathologic and genetic profiling from single tumor specimen may underestimate the mutational burden and somatic heterogeneity of bilateral ccRCCs. PMID- 27383413 TI - Post-operative ovarian adhesion formation after ovarian drilling: a randomized study comparing conventional laparoscopy and transvaginal hydrolaparoscopy. AB - PURPOSE: To compare conventional laparoscopic ovarian drilling (LOD) with transvaginal hydrolaparoscopy (THL) ovarian drilling in terms of ovarian adhesion formation, evaluated using office THL during follow-up in CC-resistant anovulatory patients affected by PCOS. METHODS: Prospective randomized study on 246 CC-resistant women with PCOS. The patients enrolled were divided into two groups, 123 were scheduled to undergo LOD and 123 to undergo THL ovarian drilling. Six months after the procedure all patients were offered office transvaginal hydrolaparoscopy (THL) follow-up, under local anesthesia to evaluate adhesion formation. RESULTS: Duration of the procedure was significantly shorter in the THL group in comparison with LOD group (p < 0.0001). No intra- or post operative complication was observed in any of the patients in both groups. Post operative THL follow-up after 6 months showed that 15 (15.5 %) patients in the THL group and 73 (70.2 %) in the LOD group showed the presence of ovarian adhesion. This difference was highly significant with a p value <0.0001 and a relative risk of 0.22 [95 % IC 0.133-0.350]. CONCLUSION: This study seems to indicate that THL ovarian drilling may reduce the risk of ovarian adhesion formation and could be used as a safe and effective option to reduce ovarian adhesion formation in patients undergoing ovarian drilling. PMID- 27383414 TI - Cambrian suspension-feeding tubicolous hemichordates. AB - BACKGROUND: The combination of a meager fossil record of vermiform enteropneusts and their disparity with the tubicolous pterobranchs renders early hemichordate evolution conjectural. The middle Cambrian Oesia disjuncta from the Burgess Shale has been compared to annelids, tunicates and chaetognaths, but on the basis of abundant new material is now identified as a primitive hemichordate. RESULTS: Notable features include a facultative tubicolous habit, a posterior grasping structure and an extensive pharynx. These characters, along with the spirally arranged openings in the associated organic tube (previously assigned to the green alga Margaretia), confirm Oesia as a tiered suspension feeder. CONCLUSIONS: Increasing predation pressure was probably one of the main causes of a transition to the infauna. In crown group enteropneusts this was accompanied by a loss of the tube and reduction in gill bars, with a corresponding shift to deposit feeding. The posterior grasping structure may represent an ancestral precursor to the pterobranch stolon, so facilitating their colonial lifestyle. The focus on suspension feeding as a primary mode of life amongst the basal hemichordates adds further evidence to the hypothesis that suspension feeding is the ancestral state for the major clade Deuterostomia. PMID- 27383415 TI - The Synthesis and Evaluation of Arctigenin Amino Acid Ester Derivatives. AB - The use of arctigenin (ARG), a traditional medicine with many pharmacological activities, has been restricted due to its poor solubility in water. Five amino acid derivatives of ARG have been synthesized using glycine, o-alanine, valine, leucine, and isoleucine, which have t-butyloxy carbonyl (BOC) as a protective group. In this study, we examined the effects of removing these protective groups. The results showed that the amino acid derivatives have better solubility and nitrite-clearing ability than ARG. Among the compounds tested, the amino acid derivatives without protective group were the best. Based on these results, ARG and its two amino acid derivatives without protective group (ARG8, ARG10) were selected to evaluate their anti-tumor activity in vivo at a dosage of 40 mg/kg. The results indicated that ARG8 and ARG10 both exhibit more anti-tumor activity than ARG in H22 tumor-bearing mice. The tumor inhibition rates of ARG8 and ARG10 were 69.27 and 43.58%, which was much higher than ARG. Furthermore, the mice treated with these compounds exhibited less damage to the liver, kidney and immune organs compared with the positive group. Furthermore, ARG8 and ARG10 improved the serum cytokine levels significantly compared to ARG. In brief, this study provides a method to improve the water solubility of drugs, and we also provide a reference basis for new drug development. PMID- 27383416 TI - CsBi4Te6: a new facile synthetic method and mid-temperature thermoelectric performance. AB - CsBi4Te6 is one of the best performing low-temperature thermoelectric (TE) materials. However, it has not received worldwide intensive investigation due to the limitation of synthetic methods. Here we report a new facile approach by not using the reactive Cs metal and the mid-temperature TE properties have been studied for the first time. PMID- 27383417 TI - Bacterial Vaginosis Screening and Treatment in Pregnant Women. AB - The American College of Obstetricians and Gynecologists, the Centers for Disease Control and Prevention, and the US Preventive Services Task Force recommend against routinely screening asymptomatic pregnant women for bacterial vaginosis (BV). Although asymptomatic BV has been associated with preterm birth, there is insufficient evidence demonstrating that treatment of asymptomatic BV improves outcomes. Conversely, women who have symptomatic BV should be treated to relieve their symptoms. This brief report provides an overview of BV, reviews the evidence regarding screening and treating BV in pregnant women, and summarizes treatment recommendations for pregnant women who have symptomatic BV. PMID- 27383418 TI - Gen1 and Eme1 Play Redundant Roles in DNA Repair and Meiotic Recombination in Mice. AB - Resolution of the Holliday junction (HJ) is essential for homologous recombination and DNA repair. In Saccharomyces cerevisiae, HJ resolvase Yen1 and the Mus81-Mms4 complex are redundant in DNA damage repair. In cultured mammalian cells, such redundancy also exists between Yen1 ortholog GEN1 and the Mus81-Mms1 ortholog MUS81-EME1. In this report, we further tested if GEN1 and EME1 redundantly affect HJ-related physiological processes in mice. We found that combined homozygous mutations of Gen1 and Eme1 led to synthetic lethality during early embryonic stages. Homozygous Gen1 mutations did not cause DNA repair deficiency in mouse embryonic fibroblast (MEF) cells, but made heterozygous Eme1 mutant MEFs more sensitive to various DNA-damaging reagents. Gen1 mutations also reduced the meiotic recombination efficiency in Eme1 mutant mice. These results suggest that Gen1 and Eme1 play redundant roles in DNA repair and meiotic recombination in vivo. PMID- 27383419 TI - Variation in the circularly polarized light reflection of Lomaptera (Scarabaeidae) beetles. AB - An extended spectroscopic study on the left-through-left circularly polarized reflection spectra of a large number of beetles from the Australasian Scrabaeidae:Cetoniinae of the Lomaptera genus was undertaken. We have obtained a five-category spectral classification. The principal spectral features, which even within the genus range from blue to infrared, are related to structural chirality in the beetle shells. The detailed features of each spectral classification are related to different structural perturbations of the helix, including various pitch values and abrupt twist defects. These spectral characteristics and associated shell structures are confirmed on the basis of simple modelling. An important conclusion from our study is that the simple helical structure resulting in a single symmetric Bragg peak is not the dominant spectral type. Rather the reality is a rich tapestry of spectral types. One intriguing specimen is identified via a scanning electron micrograph to consist of a double interstitial helix leading to a particular double-peak spectrum. PMID- 27383420 TI - Wavelength-specific forward scattering of light by Bragg-reflective iridocytes in giant clams. AB - A surprising recent discovery revealed that the brightly reflective cells ('iridocytes') in the epithelia of giant clams actually send the majority of incident photons 'forward' into the tissue. While the intracellular Bragg reflectors in these cells are responsible for their colourful back reflection, Mie scattering produces the forward scattering, thus illuminating a dense population of endosymbiotic, photosynthetic microalgae. We now present a detailed micro-spectrophotometric characterization of the Bragg stacks in the iridocytes in live tissue to obtain the refractive index of the high-index layers (1.39 to 1.58, average 1.44 +/- 0.04), the thicknesses of the high- and low-index layers (50-150 nm), and the numbers of pairs of layers (2-11) that participate in the observed spectral reflection. Based on these measurements, we performed electromagnetic simulations to better understand the optical behaviour of the iridocytes. The results open a deeper understanding of the optical behaviour of these cells, with the counterintuitive discovery that specific combinations of iridocyte diameter and Bragg-lamellar spacing can produce back reflection of the same colour that is also scattered forward, in preference to other wavelengths that are scattered at higher angles. We find for all values of size and wavelength investigated that more than 90% of the incident energy is carried by the photons that are scattered in the forward direction; while this forward scattering from each iridocyte shows very narrow angular dispersion (ca +/-6 degrees ), the multiplicative scattering from a layer of ca 20 iridocytes broadens this dispersion to a cone of approximately +/-90 degrees . This understanding of the complex biophotonic dynamics enhances our comprehension of the physiologically, ecologically and evolutionarily significant light environment inside the giant clam, which is diffuse and nearly white at small tissue depths and downwelling, relatively monochromatic, and can be the same colour as the back-reflected light at greater depths in the tissue. Originally thought to be unique, cells of similar structure and photonic activity are now recognized in other species, where they serve other functions. The behaviour of the iridocytes opens possible new considerations for conservation and management of the valuable giant clam resource and new avenues for biologically inspired photonic applications. PMID- 27383421 TI - Coupling volume-excluding compartment-based models of diffusion at different scales: Voronoi and pseudo-compartment approaches. AB - Numerous processes across both the physical and biological sciences are driven by diffusion. Partial differential equations are a popular tool for modelling such phenomena deterministically, but it is often necessary to use stochastic models to accurately capture the behaviour of a system, especially when the number of diffusing particles is low. The stochastic models we consider in this paper are 'compartment-based': the domain is discretized into compartments, and particles can jump between these compartments. Volume-excluding effects (crowding) can be incorporated by blocking movement with some probability. Recent work has established the connection between fine- and coarse-grained models incorporating volume exclusion, but only for uniform lattices. In this paper, we consider non uniform, hybrid lattices that incorporate both fine- and coarse-grained regions, and present two different approaches to describe the interface of the regions. We test both techniques in a range of scenarios to establish their accuracy, benchmarking against fine-grained models, and show that the hybrid models developed in this paper can be significantly faster to simulate than the fine grained models in certain situations and are at least as fast otherwise. PMID- 27383423 TI - The unusual hydridicity of a cobalt bound Si-H moiety. AB - A paramagnetic cobalt-SiH intermediate possessing the Co-(eta(1)-H-Si) moiety was studied using various spectroscopic techniques. Frozen solution ENDOR experiments show a Co-H distance of ~1.53 A and a Si-Co-H angle of ~15 degrees , whereas XRD data suggest a TBP geometry about a Co(ii) centre. Its stepwise deprotonation with base followed by dehalogenation was identified experimentally and theoretically. PMID- 27383422 TI - Phylogenetic analysis of human rhinoviruses collected over four successive years in Sydney, Australia. AB - BACKGROUND: Human rhinoviruses (HRV) cause a wide spectrum of disease, ranging from a mild influenza-like illness (ILI) to severe respiratory infection. Molecular epidemiological data are limited for HRV circulating in the Southern Hemisphere. OBJECTIVES: To identify the species and genotypes of HRV from clinical samples collected in Sydney, Australia, from 2006 to 2009. METHODS: Combined nose and throat swabs or nasopharyngeal aspirates collected from individuals with ILI were tested for HRV using real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Sequencing data of 5'UTR and VP4/VP2 coding regions on RT-PCR-positive specimens were analysed. RESULTS: Human rhinoviruses were detected by real-time PCR in 20.9% (116/555) of samples tested. Phylogenetic analysis of 5'UTR and VP4/VP2 on HRV-positive samples was concordant in the grouping of HRV A and B species but not HRV C species. Eighty per cent (16/20) of sequences that grouped as HRV C in the VP4/VP2 tree clustered as HRV A, alongside some previously described C strains as subspecies C/A. Discordant branching was seen within HRV A group: two sequences clustering as A in the VP4/VP2 tree branched within the C/A subspecies in the 5'UTR tree, and one sequence showed identity to different HRV A strains in the two genes. The prevalence of HRV C and C/A species was greater in paediatric compared to adult patients (47.9% vs 25.5%, P = .032). CONCLUSION: Human rhinoviruses are a common cause of respiratory infections, and HRV C is present in the Southern Hemisphere. Sequencing of multiple HRV regions may be necessary to determine exact phylogenetic relationships. PMID- 27383424 TI - Science Concierge: A Fast Content-Based Recommendation System for Scientific Publications. AB - Finding relevant publications is important for scientists who have to cope with exponentially increasing numbers of scholarly material. Algorithms can help with this task as they help for music, movie, and product recommendations. However, we know little about the performance of these algorithms with scholarly material. Here, we develop an algorithm, and an accompanying Python library, that implements a recommendation system based on the content of articles. Design principles are to adapt to new content, provide near-real time suggestions, and be open source. We tested the library on 15K posters from the Society of Neuroscience Conference 2015. Human curated topics are used to cross validate parameters in the algorithm and produce a similarity metric that maximally correlates with human judgments. We show that our algorithm significantly outperformed suggestions based on keywords. The work presented here promises to make the exploration of scholarly material faster and more accurate. PMID- 27383425 TI - Auditory verbal hallucinations: neuroimaging and treatment. AB - Auditory verbal hallucinations (AVH) are a frequently occurring phenomenon in the general population and are considered a psychotic symptom when presented in the context of a psychiatric disorder. Neuroimaging literature has shown that AVH are subserved by a variety of alterations in brain structure and function, which primarily concentrate around brain regions associated with the processing of auditory verbal stimuli and with executive control functions. However, the direction of association between AVH and brain function remains equivocal in certain research areas and needs to be carefully reviewed and interpreted. When AVH have significant impact on daily functioning, several efficacious treatments can be attempted such as antipsychotic medication, brain stimulation and cognitive-behavioural therapy. Interestingly, the neural correlates of these treatments largely overlap with brain regions involved in AVH. This suggests that the efficacy of treatment corresponds to a normalization of AVH-related brain activity. In this selected review, we give a compact yet comprehensive overview of the structural and functional neuroimaging literature on AVH, with a special focus on the neural correlates of efficacious treatment. PMID- 27383426 TI - Overexpression of BAG3 Attenuates Hypoxia-Induced Cardiomyocyte Apoptosis by Inducing Autophagy. AB - BACKGROUND: Hypoxia is a well-known factor in the promotion of apoptosis, which contributes to the development of numerous cardiac diseases, such as heart failure and myocardial infarction. Inhibiting apoptosis is an important therapeutic strategy for the treatment of related heart diseases caused by ischemia/hypoxic injury. Previous studies have demonstrated that BAG3 plays an important role in cardiomyocyte apoptosis and survival. However, the role of BAG3 in hypoxia-induced cardiomyocyte apoptosis remains to be clarified. Here, we demonstrate that BAG3 is induced by hypoxia stimuli in cultured cardiomyocytes. METHODS: BAG3 expression level was measured in H9c2 cells treated with hypoxia for 48 h. Cell proliferation and apoptosis were tested using MTT assay and Annexin V FITC-PI staining assay, respectively. The mRNA or protein expression level of BAG3, LC3-I, LC3-II, Atg5, NF-x03BA;B p65 and phosphorylated NF-x03BA;B p65 were assessed by qRT-PCR and western blot assay, respectively. Resluts: Overexpression of BAG3 inhibited cell apoptosis and promoted proliferation in hypoxia-injured H9c2 cells. Furthermore, autophagy and NF-x03BA;B were activated by BAG3 overexpression, and the NF-x03BA;B inhibitor PDTC could inhibit the activation of autophagy induced by BAG3 overexpression. In addition, the autophagy inhibitor 3-MA partly impeded the inhibitory effect of BAG3 on hypoxia induced cardiomyocyte apoptosis. CONCLUSION: these results suggested that overexpression of BAG3 promoted cell proliferation and inhibited apoptosis by activating autophagy though the NF-x03BA;B signaling pathway in hypoxia-injured cardiomyocytes. PMID- 27383427 TI - Anti-inflammatory effect of exclusive enteral nutrition in patients with juvenile idiopathic arthritis. AB - OBJECTIVES: There is extensive evidence for an influence of gut microbiota on the immune system, which has consequences for inflammatory diseases. Exclusive enteral nutrition (EEN), which may change the gut microbiota, is an effective anti-inflammatory treatment for Crohn's disease in children. We wanted to explore the immediate anti-inflammatory effect of EEN in children with juvenile idiopathic arthritis (JIA). METHODS: Thirteen patients with JIA (7-17 years of age), in a disease flare-up, were included in the study. Six children dropped out within 1.5-2.0 weeks of treatment, and seven patients continued, constituting the study cohort. EEN was given for three to eight weeks, with clinical and laboratory status assessed before and after treatment periods. In addition to conventional laboratory tests, 92 inflammatory proteins were analysed with a multiplex system (Proseek Multiplex Inflammation I, Olink Bioscience). RESULTS: EEN had a significant anti-inflammatory effect on active joints (p=0.031), JADAS27 (p=0.016) and morning stiffness (p=0.031). In the multiplex analysis of inflammatory proteins, MMP-1 (matrix metalloproteinase), involved in the degradation of collagens in chondrocytes, decreased significantly (p=0.047), as did MCP-4 (p=0.031) and 4E-BP1 (p=0.031). CONCLUSIONS: Exclusive enteral nutrition for three to eight weeks had anti-inflammatory effect in all children with JIA that continued with EEN for more than two weeks. The study is only exploratory but the result supports an immunologically important role for the intestinal canal in these patients. PMID- 27383428 TI - Bayesian shrinkage approach for a joint model of longitudinal and survival outcomes assuming different association structures. AB - The joint modeling of longitudinal and survival data has recently received much attention. Several extensions of the standard joint model that consists of one longitudinal and one survival outcome have been proposed including the use of different association structures between the longitudinal and the survival outcomes. However, in general, relatively little attention has been given to the selection of the most appropriate functional form to link the two outcomes. In common practice, it is assumed that the underlying value of the longitudinal outcome is associated with the survival outcome. However, it could be that different characteristics of the patients' longitudinal profiles influence the hazard. For example, not only the current value but also the slope or the area under the curve of the longitudinal outcome. The choice of which functional form to use is an important decision that needs to be investigated because it could influence the results. In this paper, we use a Bayesian shrinkage approach in order to determine the most appropriate functional forms. We propose a joint model that includes different association structures of different biomarkers and assume informative priors for the regression coefficients that correspond to the terms of the longitudinal process. Specifically, we assume Bayesian lasso, Bayesian ridge, Bayesian elastic net, and horseshoe. These methods are applied to a dataset consisting of patients with a chronic liver disease, where it is important to investigate which characteristics of the biomarkers have an influence on survival. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27383429 TI - Natural Killer Cell Deficits Aggravate Allergic Rhinosinusitis in a Murine Model. AB - OBJECTIVE: Defective innate immune functions can contribute to chronic rhinosinusitis (RS). Recently, it has been reported that chronic RS patients show impaired function of natural killer (NK) cells. We investigated the role of NK cells in eosinophilic inflammation in an allergic RS mouse model. METHODS: Mice sensitized to ovalbumin (OVA) by intraperitoneal injection received nasal challenges with OVA for 5 weeks. NK cell depletion was achieved by intraperitoneal injections of anti-asialo ganglio-N-tetraosylceramide (ASGM1) antibodies 10 days before OVA sensitization and every 5 days thereafter until sacrifice. Sinonasal complex samples were evaluated histologically, and IL-4, IL 5, IL-13, IFN-gamma, MIP-2, and eotaxin levels were measured in the nasal lavage fluid. Differential white blood cell counts were also obtained. RESULTS: Allergic RS mice showed significantly more eosinophilic inflammation in the sinonasal mucosa, elevated levels of IL-4, IL-5, IL-13, and eotaxin in the nasal lavage fluid, and peripheral blood eosinophilia compared to control mice. The depletion of NK cells by anti-ASGM1 treatment induced more prominent eosinophilic inflammation and increased secretion of IL-5 and peripheral blood eosinophilia in allergic RS mice. CONCLUSION: The depletion of NK cells aggravates allergen induced sinonasal eosinophilic inflammation, suggesting that impaired NK cell activity may be an exacerbating factor in eosinophilic chronic RS. PMID- 27383430 TI - Artificially sweetened taste of insulin resistance? PMID- 27383444 TI - A multi-stacked hyperporous silicon flake for highly active solar hydrogen production. AB - 3D multi-stacked hyperporous silicon flakes (MHSFs) are prepared via a selective chemical reduction of natural clay minerals bearing MgO negative catalyst layers. The resultant MHSFs are used as a photocatalyst for solar-driven hydrogen evolution and exhibit the highest photocatalytic acitivty (1031 MUmol H2 h(-1) g( 1) Si) coupled with a Pt cocatalyst. PMID- 27383431 TI - Increased salt tolerance with overexpression of cation/proton antiporter 1 genes: a meta-analysis. AB - Cation/proton antiporter 1 (CPA1) genes encode cellular Na+ /H+ exchanger proteins, which act to adjust ionic balance. Overexpression of CPA1s can improve plant performance under salt stress. However, the diversified roles of the CPA1 family and the various parameters used in evaluating transgenic plants over expressing CPA1s make it challenging to assess the complex functions of CPA1s and their physiological mechanisms in salt tolerance. Using meta-analysis, we determined how overexpression of CPA1s has influenced several plant characteristics involved in response and resilience to NaCl stress. We also evaluated experimental variables that favour or reduce CPA1 effects in transgenic plants. Viewed across studies, overexpression of CPA1s has increased the magnitude of 10 of the 19 plant characteristics examined, by 25% or more. Among the ten moderating variables, several had substantial impacts on the extent of CPA1 influence: type of culture media, donor and recipient type and genus, and gene family. Genes from monocotyledonous plants stimulated root K+ , root K+ /Na+ , total chlorophyll, total dry weight and root length much more than genes from dicotyledonous species. Genes transformed to or from Arabidopsis have led to smaller CPA1-induced increases in plant characteristics than genes transferred to or from other genera. Heterogeneous expression of CPA1s led to greater increases in leaf chlorophyll and root length than homologous expression. These findings should help guide future investigations into the function of CPA1s in plant salt tolerance and the use of genetic engineering for breeding of resistance. PMID- 27383445 TI - Sjogren syndrome. AB - Sjogren syndrome (SjS) is a systemic autoimmune disease that primarily affects the exocrine glands (mainly the salivary and lacrimal glands) and results in the severe dryness of mucosal surfaces, principally in the mouth and eyes. This disease predominantly affects middle-aged women, but can also be observed in children, men and the elderly. The clinical presentation of SjS is heterogeneous and can vary from sicca symptoms to systemic disease (characterized by peri epithelial lymphocytic infiltration of the affected tissue or the deposition of the immune complex) and lymphoma. The mechanism underlying the development of SjS is the destruction of the epithelium of the exocrine glands, as a consequence of abnormal B cell and T cell responses to the autoantigens Ro/SSA and La/SSB, among others. Diagnostic criteria for SjS include the detection of autoantibodies in patient serum and histological analysis of biopsied salivary gland tissue. Therapeutic approaches for SjS include both topical and systemic treatments to manage the sicca and systemic symptoms of disease. SjS is a serious disease with excess mortality, mainly related to the systemic involvement of disease and the development of lymphomas in some patients. Knowledge of SjS has progressed substantially, but this disease is still characterized by sicca symptoms, the systemic involvement of disease, lymphocytic infiltration to exocrine glands, the presence of anti-Ro/SSA and anti-La/SSB autoantibodies and the increased risk of lymphoma in patients with SjS. PMID- 27383446 TI - Biotransformation: a green and efficient way of antioxidant synthesis. AB - Antioxidant compounds play a vital role in human physiology. They prevent the oxidation of biomolecules by scavenging free radicals produced during physiochemical processes and/or as a result of several pathological states. A balance between the reactive oxygen species (free radicals) and antioxidants is essential for proper physiological conditions. Excessive free radicals cause oxidative stress which can lead to several human diseases. Therefore, synthesis of the effective antioxidants is crucial in managing the oxidative stress. Biotransformation has evolved as an effective technique for the production of structurally diverse molecules with a wide range of biological activities. This methodology surpasses the conventional chemical synthesis due to the fact that enzymes, being specific in nature, catalyze reactions affording products with excellent regio- and stereoselectivities. Structural transformation of various classes of compounds such as alkaloids, steroids, flavonoids, and terpenes has been carried out through this technique. Several bioactive molecules, especially those having antioxidant potential have also been synthesized by using different biotransformation techniques and enzymes. Hydroxylated, glycosylated, and acylated derivatives of phenols, flavonoids, cinnamates, and other molecules have proven abilities as potential antioxidants. A critical review of the biotransformation of these compounds into potent antioxidant metabolites is presented here. PMID- 27383447 TI - Endo-beta-Glucosidase Tag Allows Dual Detection of Fusion Proteins by Fluorescent Mechanism-Based Probes and Activity Measurement. AB - beta-Glucoside-configured cyclophellitols are activity-based probes (ABPs) that allow sensitive detection of beta-glucosidases. Their applicability to detect proteins fused with beta-glucosidase was investigated in the cellular context. The tag was Rhodococcus sp. M-777 endoglycoceramidase II (EGCaseII), based on its lack of glycans and ability to hydrolyze fluorogenic 4-methylumbelliferyl beta-d lactoside (an activity absent in mammalian cells). Specific dual detection of fusion proteins was possible in vitro and in situ by using fluorescent ABPs and a fluorogenic substrate. Pre-blocking with conduritol beta-epoxide (a poor inhibitor of EGCaseII) eliminated ABP labeling of endogenous beta-glucosidases. ABPs equipped with biotin allowed convenient purification of the fusion proteins. Diversification of ABPs (distinct fluorophores, fluorogenic high-resolution detection moieties) should assist further research in living cells and organisms. PMID- 27383448 TI - Coexposure to silver nanoparticles and ultraviolet A synergistically enhances the phosphorylation of histone H2AX. AB - Owing to the wide application of silver nanoparticles (AgNPs), the assessment of health risks associated with their use is of great importance. In this study, we revealed that the potential genotoxicity of AgNPs was enhanced by ultraviolet A (UVA) exposure. Three cultured cell lines were treated with AgNPs, followed by exposure to UVA. AgNPs induced phosphorylation of histone H2AX (gamma-H2AX) following the formation of DNA double-strand breaks (DSBs), which was synergistically enhanced by UVA exposure. Enhanced gamma-H2AX was observed only in cell lines that positively took up AgNPs, and microsized Ag particles, which were difficult to incorporate into cells, showed no gamma-H2AX. Incorporation of AgNPs was not increased by UVA exposure. AgNO3 treatment followed by UVA exposure also induced a marked increase in gamma-H2AX, indicating that the enhanced gamma H2AX was attributed to Ag ions released from AgNPs. Ag ions reacted with the -SH group of antioxidant molecules, such as glutathione, and induced intracellular oxidative conditions. 8-Hydroxy-2'-deoxyguanosine was formed in the cells treated with AgNPs, which was augmented by UVA irradiation, suggesting that intracellular oxidation caused oxidative DNA damage, leading to the enhanced formation of DSBs and gamma-H2AX. Ag has been considered a safe metal; however, our results provide important insights into the influence of sunlight on the genotoxic potency of AgNPs. PMID- 27383449 TI - Inactivation of viruses during a new manufacturing process of alpha2 macroglobulin from Cohn Fraction IV by dry-heat treatment. AB - BACKGROUND: alpha2-Macroglobulin (alpha2-M) has a curative effect on radiation injury. Virus transmission through plasma derivatives is still not risk-free. Effect of dry heat on alpha2-M activity and virus inactivation by dry heat in a new manufacturing process of alpha2-M were studied. STUDY DESIGN AND METHODS: Effects of 100 degrees C for 30 minutes, 80 degrees C for 72 hours, and lyophilization on alpha2-M activity were detected, and stabilizing agents were optimized. Effect of a treatment at 100 degrees C for 30 minutes has been tested on a range of viruses and characteristics change of alpha2-M was investigated. RESULTS: More than 90 and 80% alpha2-M activity recovery were reserved after treatment at 100 degrees C for 30 minutes and 80 degrees C for 72 hours, respectively. A concentration of 0.05 mol/L histidine presented a better protecting effect for alpha-M activity. No substantial changes were observed in the characteristics of alpha2-M compared with the untreated. By lyophilization and dry-heat treatment at 100 degrees C for 30 minutes, murine encephalomyocarditis virus and pseudorabies virus (PRV) were inactivated below detectable level within 5 minutes (virus titers reduction >= 5.75 log) and 30 minutes (virus titers reduction >= 6.00 log), respectively. Bovine viral diarrhea virus and porcine parvovirus were inactivated by 4.29 and 2.46 log reduction, respectively. CONCLUSION: Treatment at 100 degrees C for 30 minutes could improve the virus safety of alpha2-M with a slight activity loss. PMID- 27383450 TI - New Approach to Create TiO2(B)/Carbon Core/Shell Nanotubes: Ideal Structure for Enhanced Lithium Ion Storage. AB - To achieve uniform carbon coating on TiO2 nanomaterials, high temperature (>500 degrees C) annealing treatment is a necessity. However, the annealing treatment inevitably leads to the strong phase transformation from TiO2(B) with high lithium ion storage (LIS) capacity to anatase with low LIS one as well as the damage of nanostructures. Herein, we demonstrate a new approach to create TiO2(B)/carbon core/shell nanotubes (C@TBNTs) using a long-chain silane polymethylhydrosiloxane (PMHS) to bind the TBNTs by forming Si-O-Ti bonds. The key feature of this work is that the introduction of PMHS onto TBNTs can afford TBNTs with very high thermal stability at higher than 700 degrees C and inhibit the phase transformation from TiO2(B) to anatase. Such a high thermal property of PMHS-TBNTs makes them easily coated with highly graphitic carbon shell via CVD process at 700 degrees C. The as-prepared C@TBNTs deliver outstanding rate capability and electrochemical stability, i.e., reversible capacity above 250 mAh g(-1) at 10 C and a high specific capacity of 479.2 mAh g(-1) after 1000 cycles at 1 C. As far as we know, the LIS performance of our sample is the highest among the previously reported TiO2(B) anode materials. PMID- 27383451 TI - Home care for children with multiple complex chronic conditions at the end of life: The choice of hospice versus home health. AB - Families desire to bring their children home at end of life, and this creates a variety of unique care needs at home. This study analyzed the child and family factors associated with hospice versus home health care use in the last year of life among children with multiple complex chronic conditions. Using the Andersen Behavioral Healthcare Utilization Model, the predisposing, enabling, and need factors of the child and family were shown to be significant predictors of hospice and home health care use. Hospice and home health care have advantages, and families may wish to use the service that best fits their needs. PMID- 27383452 TI - Editor's Note. PMID- 27383453 TI - Light Harvesting and White-Light Generation in a Composite of Carbon Dots and Dye Encapsulated BSA-Protein-Capped Gold Nanoclusters. AB - Several strategies have been adopted to design an artificial light-harvesting system in which light energy is captured by peripheral chromophores and it is subsequently transferred to the core via energy transfer. A composite of carbon dots and dye-encapsulated BSA-protein-capped gold nanoclusters (AuNCs) has been developed for efficient light harvesting and white light generation. Carbon dots (C-dots) act as donor and AuNCs capped with BSA protein act as acceptor. Analysis reveals that energy transfer increases from 63 % to 83 % in presence of coumarin dye (C153), which enhances the cascade energy transfer from carbon dots to AuNCs. Bright white light emission with a quantum yield of 19 % under the 375 nm excitation wavelength is achieved by changing the ratio of components. Interesting findings reveal that the efficient energy transfer in carbon-dot metal-cluster nanocomposites may open up new possibilities in designing artificial light harvesting systems for future applications. PMID- 27383454 TI - Intensive adherence counselling for HIV-infected individuals failing second-line antiretroviral therapy in Johannesburg, South Africa. AB - OBJECTIVE: In resource-limited settings, where genotypic drug resistance testing is rarely performed and poor adherence is the most common reason for treatment failure, programmatic approaches to handling treatment failure are essential. This study was performed to describe one such approach to adherence optimisation. METHODS: This was a single-arm study of patients on second-line protease inhibitor (PI)-based antiretroviral therapy (ART) with a HIV-1 RNA >=400 copies/ml in Johannesburg, South Africa, between 1 March 2012 and 1 December 2013. Patients underwent enhanced adherence counselling. Those with improved adherence and a repeat viral load of >1000 copies/ml underwent HIV-1 drug resistance testing. We describe results using simple proportions and 95% confidence intervals. RESULTS: Of the 400 patients who underwent targeted adherence counselling after an elevated viral load on second-line ART, 388 (97%) underwent repeat viral load testing. Most of these (n = 249; 64%, 95% CI 59-69) resuppressed (<400 copies/ml) on second line. By the end of follow-up (1 March 2014), among the 139 (36%, 95% CI: 31-41%), who did not initially resuppress after being targeted, 106 had a viral load >400 copies/ml, 11 switched to third line, 5 were awaiting third line, 4 had died and 13 were lost to follow-up. Among the unsuppressed, 48 successfully underwent resistance testing with some resistance detected in most (41/48). CONCLUSIONS: Most (64%) second-line treatment failure in this clinic is related to adherence and can be overcome with careful adherence support. Controlled interventions are needed to determine what the optimal approach is to improving second-line outcomes and reducing the need for third-line ART. PMID- 27383455 TI - Ion-Image Interactions and Phase Transition at Electrolyte-Metal Interfaces. AB - The arrangement of ions near a metallic electrode is crucial to energy storage in electrical double-layer capacitors. Classic Poisson-Boltzmann theory predicts that the charge stored in the double layer is a continuous function of applied voltage. However, recent experiments and simulations strongly suggest the presence of a voltage-induced first-order phase transition in the electrical double layer, leading to a hysteretic response: the capacitance-voltage relation is dependent on whether the voltage is increasing or decreasing. By developing a simple analytical model, we show that ion-image interaction could explain this phase transition. Moreover, our model shows that the presence of phase transition depends on the bulk energy of the ionic liquid. Our results justify mixing ionic liquids with solvents as a way to achieve large capacitance and avoid hysteresis. PMID- 27383456 TI - New insights into cell non-autonomous mechanisms of the C. elegans hypoxic response. AB - The hypoxic response is a well-studied and highly conserved biological response to low oxygen availability. First described more than 20 y ago, the traditional model for this response is that declining oxygen levels lead to stabilization of hypoxia-inducible transcription factors (HIFs), which then bind to hypoxia responsive elements (HREs) in target genes to mediate the transcriptional changes collectively known as the hypoxic response.(1,2) Recent work in C. elegans has forced a re-evaluation of this model by indicating that the worm HIF (HIF-1) can mediate effects in a cell non-autonomous fashion and, in at least one case, increase expression of an intestinal hypoxic response target gene in cells lacking HIF-1. PMID- 27383457 TI - Cost comparison of kidney transplant versus dialysis in Brazil. AB - This study aimed to compare the direct medical costs of renal transplantation and renal replacement therapies, specifically hemodialysis and peritoneal dialysis, from the perspective of the Brazilian Unified National Health System (SUS). Renal replacement therapies costs were based on data published in the literature. Cost items for kidney transplant were identified in a private hospital based on procedure codes used for charging the SUS, and other items were taken from the literature. In the four years covered by the study, cadaver kidney transplant generated per-patient savings of BRL 37,000 and BRL 74,000 compared to hemodialysis and peritoneal dialysis, respectively. Savings were even greater with living donor kidney transplant: BRL 46,000 and BRL 82,000 compared to hemodialysis and peritoneal dialysis, respectively. This result, together with survival and quality-of-life analyses, characterizes kidney transplant as the best clinical and financial alternative, thus supporting public policies for organ transplants in Brazil. PMID- 27383458 TI - The challenging nature of gathering evidence and analyzing the judicialization of health in BrazilThe authors replyEstudos publicados em periodicos indexados sobre decisoes judiciais para acesso a medicamentos no Brasil: uma revisao sistematicaBetween the court and the clinic: lawsuits for medicines and the right to health in BrazilMedicamentos biologicos para artrite reumatoidePortaria no 2.981, de 26 de novembro de 2009. Dispoe sobre o componente especializado da Assistencia Farmaceutica (revogada pela Portaria no 1.554/2013).The challenging nature of gathering evidence and analyzing the judicialization of health in Brazil. PMID- 27383459 TI - Where is the right to abortion? Comment on the documentary Zika, The Film. PMID- 27383460 TI - Correction to The Carboxyl Terminus of Eremomycin Facilitates Binding to the Non d-Ala-d-Ala Segment of the Peptidoglycan Pentapeptide Stem. PMID- 27383462 TI - Performance improvement in flexible polymer solar cells based on modified silver nanowire electrode. AB - In this work, an efficient flexible polymer solar cell was achieved by controlling the UV-ozone treatment time of silver nanowires (Ag NWs) used in the electrode and combined with other modification materials. Through optimizing the time of UV-ozone treatment, it is shown that Ag NWs electrode treated by UV-ozone for 10 s improves the power conversion efficiency (PCE) of the device based on the blend of poly(3-hexylthiophene)(P3HT): [6,6]-phenyl C61-butyric acid methyl ester (PC61BM) from 0.76% to 1.34%. After treatment by UV-ozone, Ag NWs electrodes exhibit several promising characteristics, including high optical transparency, low sheet resistance and superior surface work function. As a consequence, the performance of devices utilizing 10 s UV-ozone-treated Ag NWs with PEDOT: PSS or MoO3 as composite anode showed higher PCEs of 2.77% (2.73%) compared with that for Ag NW electrodes without UV-ozone treatment. In addition, a PCE of 5.97% in flexible polymer solar cells based on poly[4,8-bis(5-(2 ethylhexyl)thiophen-2-yl)-benzo[1,2-b:4,5-b0]dithiophene-2,6-diyl-alt-(4-(2 ethylhexyl)-3-fluorothieno[3,4-b]thiophene-)-2-carboxylate-2-6-diyl](PBDTTT EFT):[6, 6]-phenyl C71-butyric acid methyl ester (PC71BM) as a photoactive layer was obtained. PMID- 27383461 TI - The focus on sample quality: Influence of colon tissue collection on reliability of qPCR data. AB - Successful molecular analyses of human solid tissues require intact biological material with well-preserved nucleic acids, proteins, and other cell structures. Pre-analytical handling, comprising of the collection of material at the operating theatre, is among the first critical steps that influence sample quality. The aim of this study was to compare the experimental outcomes obtained from samples collected and stored by the conventional means of snap freezing and by PAXgene Tissue System (Qiagen). These approaches were evaluated by measuring rRNA and mRNA integrity of the samples (RNA Quality Indicator and Differential Amplification Method) and by gene expression profiling. The collection procedures of the biological material were implemented in two hospitals during colon cancer surgery in order to identify the impact of the collection method on the experimental outcome. Our study shows that the pre-analytical sample handling has a significant effect on the quality of RNA and on the variability of qPCR data. PAXgene collection mode proved to be more easily implemented in the operating room and moreover the quality of RNA obtained from human colon tissues by this method is superior to the one obtained by snap freezing. PMID- 27383463 TI - Methanesulfonyl Azide: Molecular Structure and Photolysis in Solid Noble Gas Matrices. AB - The parent sulfonyl azide CH3SO2N3 has been characterized in a neat form by IR (gas, matrix-isolation) and Raman (solid) spectroscopy, and its structure has been established by X-ray crystallography. In both gas phase and solid state, the azide exhibits single conformation with the azido ligand being synperiplanar to one of the two S?O groups. In the crystal molecules of CH3SO2N3 are interconnected through three-dimensional O...H-C-H...O hydrogen bonds. Upon an ArF laser (193 nm) photolysis, the azide in solid noble gas matrices splits off N2 and yields the sulfonyl nitrene CH3SO2N in the triplet ground state. Subsequent photolysis with UV light (266 nm) causes the transformation from the nitrene to the pseudo-Curtius rearrangement product CH3NSO2. The identification of the photolysis intermediates by matrix-isolation IR spectroscopy is supported by quantum chemical calculations with DFT methods. PMID- 27383464 TI - Poor sleep quality and nightmares are associated with non-suicidal self-injury in adolescents. AB - Non-suicidal self-injury (NSSI) is prevalent and is associated with increased risk of suicidal behavior in adolescents. This study examined which sleep variables are associated with NSSI, independently from demographics and mental health problems in Chinese adolescents. Participants consisted of 2090 students sampled from three high schools in Shandong, China and had a mean age of 15.49 years. Participants completed a sleep and health questionnaire to report their demographic and family information, sleep duration and sleep problems, impulsiveness, hopelessness, internalizing and externalizing problems, and NSSI. A series of regression analyses were conducted to examine the associations between sleep variables and NSSI. Of the sample, 12.6 % reported having ever engaged in NSSI and 8.8 % engaged during the last year. Univariate logistic analyses demonstrated that multiple sleep variables including short sleep duration, insomnia symptoms, poor sleep quality, sleep insufficiency, unrefreshed sleep, sleep dissatisfaction, daytime sleepiness, fatigue, snoring, and nightmares were associated with increased risk of NSSI. After adjusting for demographic and mental health variables, NSSI was significantly associated with sleeping <6 h per night, poor sleep quality, sleep dissatisfaction, daytime sleepiness, and frequent nightmares. Stepwise logistic regression model demonstrated that poor sleep quality (OR = 2.18, 95 % CI = 1.37-3.47) and frequent nightmares (OR = 2.88, 95 % CI = 1.45-5.70) were significantly independently associated with NSSI. In conclusion, while multiple sleep variables are associated with NSSI, poor sleep quality and frequent nightmares are independent risk factors of NSSI. These findings may have important implications for further research of sleep self-harm mechanisms and early detection and prevention of NSSI in adolescents. PMID- 27383465 TI - Graphene Sandwiched Mesostructured Li-Ion Battery Electrodes. AB - A deterministic graphene-sandwiched Li-ion battery electrode consisting of an integrated 3D mesostructure of electrochemically active materials and graphene is presented. As demonstrations, electrodes with active nanomaterials that coat (V2 O5 @graphene@V2 O5 cathode) or are coated by (graphene@Si@graphene anode) graphene are fabricated. These electrodes exhibit high capacities and ultralong cycle lives (the cathode can be cycled over 2000 times with minimal capacity fade). PMID- 27383466 TI - Simultaneous SAXS and SANS Analysis for the Detection of Toroidal Supramolecular Polymers Composed of Noncovalent Supermacrocycles in Solution. AB - Molecular self-assembly primarily occurs in solution. To better understand this process, techniques capable of probing the solvated state are consequently required. Small-angle scattering (SAS) has a proven ability to detect and characterize solutions, but it is rarely applied to more complex assembly shapes. Here, small-angle X-ray and neutron scattering are applied to observe toroidal assemblies in solution. Combined analysis confirms that the toroids have a core shell structure, with a pi-conjugated core and an alkyl shell into which solvent penetrates. The dimensions determined by SAS agree well with those obtained by (dried-state) atomic force microscopy. Increasing the number of naphthalene units in the molecular building block yields greater rigidity, as evidenced by a larger toroid and a reduction in solvent penetration into the shell. The detailed structural analysis demonstrates the applicability of SAS to monitor complex solution-based self-assembly. PMID- 27383467 TI - The limited use of the fluency heuristic: Converging evidence across different procedures. AB - In paired comparisons based on which of two objects has the larger criterion value, decision makers could use the subjectively experienced difference in retrieval fluency of the objects as a cue. According to the fluency heuristic (FH) theory, decision makers use fluency-as indexed by recognition speed-as the only cue for pairs of recognized objects, and infer that the object retrieved more speedily has the larger criterion value (ignoring all other cues and information). Model-based analyses, however, have previously revealed that only a small portion of such inferences are indeed based on fluency alone. In the majority of cases, other information enters the decision process. However, due to the specific experimental procedures, the estimates of FH use are potentially biased: Some procedures may have led to an overestimated and others to an underestimated, or even to actually reduced, FH use. In the present article, we discuss and test the impacts of such procedural variations by reanalyzing 21 data sets. The results show noteworthy consistency across the procedural variations revealing low FH use. We discuss potential explanations and implications of this finding. PMID- 27383468 TI - Green tea catechins are potent anti-oxidants that ameliorate sodium iodate induced retinal degeneration in rats. AB - Green tea extracts exhibit anti-oxidative and anti-inflammatory actions in different disease conditions. We hypothesized that green tea extract and its catechin constituents ameliorate sodium iodate-induced retinal degeneration in rats by counteracting oxidative stress. In this study, adult Sprague-Dawley rats were intravenously injected with a single dose of sodium iodate. Green tea extract (GTE; Theaphenon-E) or combinations of its catechin constituents, including (-)-epigallocatechin gallate (EGCG), were administered intra gastrically before injection. Live imaging analysis using confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography showed a progressive increase of degenerating profile across the retinal surface and decrease in thickness of outer nuclear layer (ONL) at Day-14 of post-injection. These lesions were significantly ameliorated by Theaphenon-E and catechin combinations with EGCG. Catechins with exclusion of EGCG did not show obvious protective effect. Histological analyses confirmed that Theaphenon-E and catechins containing EGCG protect the retina by reducing ONL disruption. Retinal protective effects were associated with reduced expression of superoxide dismutase, glutathione peroxidase and caspase-3, and suppression of 8-iso Prostaglandin F2alpha generation in the retina. In summary, GTE and its catechin constituents are potent anti-oxidants that offer neuroprotection to the outer retinal degeneration after sodium iodate insult, among which EGCG is the most active constituent. PMID- 27383469 TI - Self-Paced Exercise, Affective Response, and Exercise Adherence: A Preliminary Investigation Using Ecological Momentary Assessment. AB - Affective response to exercise may mediate the effects of self-paced exercise on exercise adherence. Fiftynine low-active (exercise <60 min/week), overweight (body mass index: 25.0-39.9) adults (ages 18-65) were randomly assigned to self paced (but not to exceed 76% maximum heart rate) or prescribed moderate intensity exercise (64-76% maximum heart rate) in the context of otherwise identical 6 month print-based exercise promotion programs. Frequency and duration of exercise sessions and affective responses (good/bad) to exercise were assessed via ecological momentary assessment throughout the 6-month program. A regression based mediation model was used to estimate (a) effects of experimental condition on affective response to exercise (path a = 0.20, SE = 0.28, f2 = 0.02); (b) effects of affective response on duration/latency of the next exercise session (path b = 0.47, SE = 0.25, f2 = 0.04); and (c) indirect effects of experimental condition on exercise outcomes via affective response (path ab = 0.11, SE = 0.06, f2 = 0.10). Results provide modest preliminary support for a mediational pathway linking self-paced exercise, affective response, and exercise adherence. PMID- 27383470 TI - Anti-Factor Xa Assay-A Changing Standard for Venous Thromboprophylaxis? PMID- 27383472 TI - "To Bluff like a Man or Fold like a Girl?" - Gender Biased Deceptive Behavior in Online Poker. AB - Evolutionary psychology suggests that men are more likely than women to deceive to bolster their status and influence. Also gender perception influences deceptive behavior, which is linked to pervasive gender stereotypes: women are typically viewed as weaker and more gullible than men. We assessed bluffing in an online experiment (N = 502), where participants made decisions to bluff or not in simulated poker tasks against opponents represented by avatars. Participants bluffed on average 6% more frequently at poker tables with female-only avatars than at tables with male-only or gender mixed avatars-a highly significant effect in games involving repeated decisions. Nonetheless, participants did not believe the avatar genders affected their decisions. Males bluffed 13% more frequently than females. Unlike most economic games employed exclusively in research contexts, online poker is played for money by tens of millions of people worldwide. Thus, gender effects in bluffing have significant monetary consequences for poker players. PMID- 27383471 TI - Unprimed, M1 and M2 Macrophages Differentially Interact with Porphyromonas gingivalis. AB - Porphyromonas gingivalis is a keystone pathogen in the development of chronic periodontitis. Tissue macrophages are amongst the first immune cells to respond to bacteria and depending on the cytokine profile at the infection site, macrophages are primed to react to infection in different ways. Priming of naive macrophages with IFN-gamma produces a classical pro-inflammatory, antibacterial M1 macrophage after TLR ligation, whereas priming with IL-4 induces an anti inflammatory tissue-repair M2 phenotype. Previous work has shown that M1 are preferentially generated in gingival tissue following infection with P. gingivalis. However, few studies have investigated the interactions of macrophage subsets with P. gingivalis cells. The aim of this study was to determine the ability of naive, M1 and M2 macrophages to phagocytose P. gingivalis and investigate how this interaction affects both the bacterial cell and the macrophage. M1 and M2 macrophages were both found to have enhanced phagocytic capacity compared with that of naive macrophages, however only the naive and M1 macrophages were able to produce a respiratory burst in order to clear the bacteria from the phagosome. P. gingivalis was found to persist in naive and M2, but not M1 macrophages for 24 hours. Phagocytosis of P. gingivalis also induced high levels of TNF-alpha, IL-12 and iNOS in M1 macrophages, but not in naive or M2 macrophages. Furthermore, infection of macrophages with P. gingivalis at high bacteria to macrophage ratios, while inducing an inflammatory response, was also found to be deleterious to macrophage longevity, with high levels of apoptotic cell death found in macrophages after infection. The activation of M1 macrophages observed in this study may contribute to the initiation and maintenance of a pro inflammatory state during chronic periodontitis. PMID- 27383473 TI - A bimodal fluorescent and photocytotoxic naphthalene diimide for theranostic applications. AB - We report on the potential of a water-soluble tetracationic quaternary ammonium naphthalene diimide (NDI) as multifunctional agent of interest for theranostic applications. The DNA binding ability of this NDI has been investigated. NDI exhibits high binding constants for G-quadruplex DNA but it is not selective for this type of DNA. Taking advantage of its intrinsic fluorescence and singlet oxygen sensitizing ability, cellular uptake, cytotoxicity and photocytotoxicity have been investigated. The intense emission in the red/NIR allows monitoring of the cell permeability of this charged tetracationic NDI, accumulating into the cell nuclei. No dark cytotoxicity has been observed on selected tumor cell lines. Irradiation of the NDI loaded cells with red light reduces cell viability up to 40% and causes a significant increase of the percentage of cells expressing gammaH2AX foci indicating DNA damage. The presence of distinct DNA damage foci inside the nucleus suggests that the NDI molecule might induce DNA damage in specific sites. To the best of our knowledge this is the first NDI exhibiting PDT activity at MUM concentration combined with low dark cytotoxicity. PMID- 27383474 TI - Corrigendum to arteriovenous fistula geometry in hybrid recanalisation of post thrombotic venous obstruction. PMID- 27383476 TI - Descriptive Halstead-Reitan study of nonimpact mild traumatic brain injury. AB - Patients subjected to severe acceleration forces in motor vehicle accidents that met criteria for uncomplicated mild traumatic brain injury (mTBI) in the absence of direct impact to the head were examined neuropsychologically using the Halstead-Reitan Neuropsychological Test Battery. The subjects were litigants and/or insurance claimants for whom there was psychometric evidence of acceptable test effort. The purpose of the study was to provide descriptive neuropsychological data for this particular clinical population. Individual test results were interpreted using inferential methods of level of performance, pathognomonic signs, score patterns, and right-left performance differences. These interpretive strategies yielded group data from which frequencies and percentages of atypical neuropsychological characteristics were calculated. The most salient clinical characteristics involved atypical right-left performance relationships on simple and more complex tests of motor function. Clinical data provided support for the possibility that a minority of nonimpact litigants or insurance claimants that sustain uncomplicated mTBI experience persistent diminishment in some neuropsychological abilities. PMID- 27383475 TI - DNA Barcoding of Metazoan Zooplankton Copepods from South Korea. AB - Copepods, small aquatic crustaceans, are the most abundant metazoan zooplankton and outnumber every other group of multicellular animals on earth. In spite of ecological and biological importance in aquatic environment, their morphological plasticity, originated from their various lifestyles and their incomparable capacity to adapt to a variety of environments, has made the identification of species challenging, even for expert taxonomists. Molecular approaches to species identification have allowed rapid detection, discrimination, and identification of cryptic or sibling species based on DNA sequence data. We examined sequence variation of a partial mitochondrial cytochrome C oxidase I gene (COI) from 133 copepod individuals collected from the Korean Peninsula, in order to identify and discriminate 94 copepod species covering six copepod orders of Calanoida, Cyclopoida, Harpacticoida, Monstrilloida, Poecilostomatoida and Siphonostomatoida. The results showed that there exists a clear gap with ca. 20 fold difference between the averages of within-specific sequence divergence (2.42%) and that of between-specific sequence divergence (42.79%) in COI, suggesting the plausible utility of this gene in delimitating copepod species. The results showed, with the COI barcoding data among 94 copepod species, that a copepod species could be distinguished from the others very clearly, only with four exceptions as followings: Mesocyclops dissimilis-Mesocyclops pehpeiensis (0.26% K2P distance in percent) and Oithona davisae-Oithona similis (1.1%) in Cyclopoida, Ostrincola japonica-Pseudomyicola spinosus (1.5%) in Poecilostomatoida, and Hatschekia japonica-Caligus quadratus (5.2%) in Siphonostomatoida. Thus, it strongly indicated that COI may be a useful tool in identifying various copepod species and make an initial progress toward the construction of a comprehensive DNA barcode database for copepods inhabiting the Korean Peninsula. PMID- 27383477 TI - Impact of a prior diagnosis of DCIS on survival from invasive breast cancer. AB - A diagnosis of invasive breast cancer after DCIS can be described as a new primary cancer or as a local invasive recurrence. It is of interest to determine if, among women with early-stage breast cancer, a past history of DCIS influences survival. We retrieved the records of 306,249 women diagnosed with stage I or stage II breast cancer between 2004 and 2012, in the surveillance, epidemiology, and end results registries database, of whom 5395 had a previous diagnosis of DCIS. For each patient, we extracted information on the year of diagnosis, age at diagnosis, tumor size, nodal status, grade, estrogen receptor status, type of surgery (lumpectomy/mastectomy), use of radiotherapy (no/yes), prior DCIS (no/yes), cause of death, and follow-up time. For each case with prior DCIS, we recorded information on the year of diagnosis of DCIS, laterality of DCIS, and treatments received for DCIS. We matched 3979 patients with a prior DCIS to 3979 patients without a prior DCIS, according to the various prognostic features of the invasive cancer. We estimated the risk of death from breast cancer for patients with invasive ductal carcinoma, with and without a prior diagnosis of DCIS. We identified 306,249 women with stage I/II breast cancer, of whom 2335 had a prior ipsilateral DCIS and 3060 had a prior contralateral DCIS. Breast cancer specific survival at 9 years was 94.6 % for patients with a prior DCIS (ipsilateral or contralateral) and was 95.2 % for patients with no prior DCIS (p = 0.32). In a matched analysis (3979 matched pairs), the hazard ratio for death from breast cancer for patients with a prior ipsilateral DCIS, compared to patients with no prior DCIS, was 0.91 (95 % CI = 0.49-1.68; p = 0.75). A prior diagnosis of ipsilateral DCIS does not impact upon the prognosis of women with early-stage invasive breast cancer. This suggests that primary breast cancers and local invasive recurrences following DCIS are similar conditions and should be treated in the same way. PMID- 27383478 TI - Breast fine needle aspiration continues to be relevant in a large academic medical center: experience from Massachusetts General Hospital. AB - Fine needle aspiration (FNA) is increasingly being supplanted by core needle biopsy. However, breast surgeons continue to rely on FNA at our institution. This retrospective study evaluated breast FNA for its diagnostic accuracy and breast cancer biomarker testing utility. All breast FNAs performed at Massachusetts General Hospital 2009-2015 were reviewed. Cytology diagnoses were compared with subsequent tissue or clinical diagnoses. Immunohistochemistry and fluorescence in situ hybridization (FISH) results using formalin-fixed paraffin-embedded (FFPE) cell blocks and histologic tissue blocks were compared. 1654 consecutive breast FNAs were included. Breast FNA demonstrated the following diagnostic performance: positive predictive value of malignant cytology diagnosis 100 %, negative predictive value of benign cytology diagnosis 97.5 %, complete sensitivity 91.6 %, and specificity 95.5 %. Concordance rates for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) immunohistochemistry, and HER2 FISH were 98.2 % (kappa = 0.95, p < 0.001), 100.0 % (kappa = 1.000, p < 0.001), 83.1 % (kappa = 0.69, p < 0.001), and 93.5 % (kappa = 0.785, p < 0.001), respectively. Review of consecutive breast FNAs in a large cohort confirmed the excellent accuracy of this biopsy technique for breast lesion diagnosis. FNA FFPE cell blocks collected in the course of routine clinical care are adequate, practical, and reliable for breast cancer biomarker testing. PMID- 27383479 TI - Evaluation of an amplicon-based next-generation sequencing panel for detection of BRCA1 and BRCA2 genetic variants. AB - The recent advances in the next-generation sequencing (NGS) technology have enabled fast, accurate, and cost-effective genetic testing. Here, we evaluated the performance of a targeted NGS panel for BRCA1/2 sequencing and confirmed its applicability in routine clinical diagnostics. We tested samples from 88 patients using the TruSeq custom panel (Illumina Inc, USA) and a MiSeq sequencer (Illumina) and compared the results to the outcomes of conventional Sanger sequencing. All 1015 sequence variations identified by Sanger sequencing were detected by NGS, except for one missense variant that might have been missed due to a rare mutation on a primer-binding site. One deletion variation, c.1909 + 12delT of BRCA2, was falsely called in all samples due to a homopolymer error. In addition, seven different single-nucleotide substitutions with low variant frequencies (range: 16.2-33.3 %) were falsely called by NGS. In a separate batch, 10 different false-positive variations were found in five samples. The overall sensitivity and positive predictive value of NGS were estimated to be 99.9 and 87.5 %, respectively. The false-positive results could be excluded by setting quality and alternative allele ratio filters and/or by visual inspection using the IGV software. Targeted NGS panel for BRCA1 and BRCA2 showed an excellent agreement with Sanger sequencing results. We therefore conclude that this NGS panel can be used for routine diagnostic method in a clinical genetic laboratory. PMID- 27383480 TI - Goodbye to the European Working Time Directive? PMID- 27383481 TI - Protective effects of Emblica officinalis (Amla) on metal-induced lipid peroxidation in human erythrocytes. AB - The protective potential of Emblica officinalis (amla) was investigated on metal induced lipid per oxidation in human erythrocytes. Increases in the levels of MDA and catalase activity were assessed as lipid per oxidation. In addition, glutathione peroxidase (GPX), glutathione (GSH), and ascorbic acid levels were assessed as antioxidant indices. Preliminary investigation of the extract exhibited a significant reduction in lipid per oxidation and an increase in antioxidant abilities, such as a decrease in MDA, GPx and GSH (P<0.05). A significant reduction in erythrocyte hemolysis induced by hydrogen peroxide was observed using amla extract (P<0.05). These findings show that amla extract has significant protective potential against lipid per oxidation. PMID- 27383482 TI - Genetic polymorphism of UDP-glucuronosyltransferase (UGT2B15) and glucuronidation of paracetamol in healthy population. AB - Inter individual variability in polymorphic UDP-glucuronosyltransferase (UGT2B15) has been associated with varied glucuronidation level. The present project was designed to determine the genetic polymorphism of UDP-glucuronosyltransferase (UGT2B15) and glucuronidation of paracetamol in healthy (male=59 and female=50) population. The association between genotype (UGT2B15) and phenotype (paracetamol glucuronidation) has been evaluated. According to trimodal model, genotypes and phenotypes were categorized as fast, intermediate and slow glucuronidators. Presence of wild type allele illustrated a UGT2B15 genotype as fast glucuronidator. The glucuronidation status was investigated by HPLC analysis of paracetamol. Ratio of paracetamol glucuronide to paracetamol was determined with two antimodes at glucuronidation ratio of 0.3 and 1.8. In our study, 7% and 12% of population was distributed as slow glucuronidators by phenotype and genotype, respectively and association between phenotype and genotype was good for analysis of glucuronidation status as displayed by kappa value (0.792). PMID- 27383483 TI - The changes in serum and whole blood rheological properties of rabbits during the progression of atherosclerosis. AB - This study aimed to evaluate the role of zinc (Zn)-supplemented with high cholesterol diet (HCD) on the serum and whole blood rheological properties of rabbits fed a HCD. Twenty-four New Zealand white rabbits were divided into three groups. The HCD group was fed a diet with 1.0% cholesterol and 1.0% olive oil. The HCD + Zn group was fed a diet with 1.0% cholesterol, 1.0% olive oil, and Zn. Blood viscosity, shear stress, and torque (%) were measured at shear rates ranging from 225 to 1875 s-1 for serum and 75-900 s-1 for whole blood. Serum viscosity and shear stress in HCD rabbits were significantly higher at all shear rates compared to controls; while whole blood viscosity and shear stress in HCD rabbits were significantly lower at all shear rates compared to controls. Viscosity and shear stress in both serum and whole blood from rabbits in the HCD + Zn group returned to normal values at all shear rates. The Zn supplemented to HCD rabbits, delays the progression of atherosclerosis. Changes in blood serum viscosity could reflect changes in non-clotting proteins, glucose, nutrients and trace elements; while changes in whole blood viscosity could result from changes in hematocrit, hemoglobin, and erythrocyte count. One of the factors responsible for increasing the serum viscosity values of HCD rabbits might be attributed to increase in Fe and decrease in Zn levels in the blood serum. PMID- 27383484 TI - Phytochemical screening, antiglycation and antioxidant activities of whole plant of Boerhavia repens L. from Cholistan, Pakistan. AB - Present study was aimed to explore a traditionally used indigenous medicinal plant Boerhavia repens (Nyctaginaceae family) of the Cholistan desert, Pakistan. Crude aqueous and methanolic extracts of the whole plant were investigated in vitro for preliminary phytochemical screening, antioxidant and antiglycation activities. Antioxidant activities were determined by total phenolic contents, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and inhibition of lipid peroxidation. For antiglycation activities browning production was noted and thiobarbituric acid (TBA) technique was used to determine glycation level. Boerhavia repens expressed considerable amounts of phytochemicals. Extract yield was found to be 4.59%-7.85% g/100g of dry matter with total phenolics ranging from 47.9- 190.77mg/GAE per g for aqueous and methanol extract respectively. Strong inhibitory effect was exhibited by methanolic extract in linoleic acid per oxidation system (86.11%, EC50=0.99mg/mL) and DPPH assay (88.65%, EC50=212.33MUg/ml). In term of browning maximum inhibition (81.50%) was exhibited by methanolic extract at 37 degrees C at third week of incubation. Both extracts expressed significant (P>0.05) and comparable inhibition of glycation level. In conclusion, Boerhavia repens showed promising antioxidant and antiglycation activities validating its therapeutic potential. PMID- 27383485 TI - Beneficial effects of bipolar hemiarthroplasty replacement and fosamax in the retrospective cohort study of refracture and mortality of hip fractured patients. AB - The epidemiological hip fracture leads to a high death rate in the elderly with osteoporosis worldwide. However, the appropriate surgical styles or anti osteoporotic therapy could prevent these patients with hip fractures from suffering refracture, but the efficacy of such treatment remains elusive for first hip fractured patients. Our retrospective analysis was conducted on 508 hip fracture patients who were enrolled from Show Chwan Memorial Hospital from January 2005 through December 2011 and followed up until the end of 2012. However, bipolar hemiarthroplasty replacement and open reduction internal fixation (ORIF) are treatment options for femoral neck and intertrochanic hip fracture in our study population. Among these patients, 82 suffered 2nd hip fracture (refracture) with femoral neck or intertrochanteric fracture and 39 died after surgical intervention accompanied complications. Kaplan-Meier analysis revealed a better outcome in patients with bipolar hemiarthroplasty replacement or fosamax therapy of hip fractured patients than those with femoral neck/ORIF and intertrochanteric/ORIF or without fosamax therapy. Multivariate cox regression analysis revealed the lowest incidence of refracture and mortality in hip fracture patients with received bipolar hemiarthroplasty replacement surgical intervention (OR=0.732, CI=0.587-0.912; P=0.006). It is therefore concluded that fosamax therapy may improve bone density and increase bone tissue repair to prevent patients with hip fracture from refracture, and bipolar hemiarthroplasty replacement may promote patients who undertake outdoor activities to produce more vitamin D than those who have received ORIF. PMID- 27383486 TI - Antiviral potential of a diterpenoid compound sugiol from Metasequoia glyptostroboides. AB - This research reports first time antiviral activity of sugiol, a diterpenoid isolated from Metasequoia glyptostroboides in terms of its ability to inhibit in vitro growth of H1N1 influenza virus. Antiviral potential of sugiol was evaluated through hcytopathogenic reduction assay using Madin-Darby canine kidney (MDCK) cell line. Sugiol (500 MUg/ml) was found to exhibit considerable anti-cytopathic effect on MDCK cell line confirming its antiviral efficacy against H1N1 influenza virus. These findings strongly reinforce the suggestion that sugiol could be a candidate of choice in combinational regimen with potential antiviral efficacy. PMID- 27383487 TI - In vitro evaluation of bioactive potential of Bacillus methylotrophicus YML008 against Propionibacterium acnes. AB - Acne vulgaris is the most common skin diseases that people experience during their lives. Thirteen rhizosphere isolates were screened against Propionibacterium acnes. The bacterium exhibited the highest activity against P. acnes was identified as Bacillus methylotrophicus YML008 by 16S rRNA gene sequencing. Scanning electron microscopy was used to assess the changes in morphology of P. acnes. Preliminary studies on the antimicrobial substance demonstrated the hydrophilic nature of compound with MIC of 0.17mg/ml and MBC of 0.3mg/ml. The cytotoxic effect of the extract was least (80% survival) as compared to benzyperoxide (40% survival). These results suggest YML008 as a promising bioresource and may be useful as a lead bacterium to develop a new type of anti-acne skin care prep to cure or prevent acne. Further, mechanism of action and proper clinical trials may be promising for this research. PMID- 27383488 TI - The effects of deferoxamine on inhibition for microglia activation and protection of secondary nerve injury after intracerebral hemorrhage in rats. AB - To investigate the effects of the iron chelatordeferoxamine (DFA) on inhibition formicroglia activation and protection of secondary nerve injury after intracerebral hemorrhage (ICH) in rats. The rats were randomly divided into sham operation group, ICH group and DFA treatment group. The collagenase was used to prepare ICH model of basal gangliain rats and 1h after the beginning of the operation, the intraperitoneal injection with DFA was arranged every 12 h and for a total of 7d. The changes of Iron ion concentration were measured at perihematomaat different time points after the medicine was given. OX42 immunohistochemical staining observed microglia change at perihematoma. ELISA method determined the changes of IL-1beta and TNF-beta content of brain tissue. Neurological deficit scores and Nissl staining were used to observe the situation of neurological function and neuronal loss of rats after DFA treatment. 1 d After the start of ICH, the concentration of iron in perihematoma was significantly higher than that of animalsin sham-operated group and could sustain for28 d. At the same time, the quantities of local microglial cells were significantly increased. After applying DFA, the concentration of iron ions in the brain tissue around the hematoma was significantly reduced, so did the number of microglial cells and activation of neurotoxic cytokines (IL-1beta and TNF-alpha content) secreted by microglial cells was significantly reduced. At the same time, the loss of neurons in the tissue around of the hematoma was significantly reduced and neurological deficit scores were significantly reduced. Iron ions which were sustainedly released by hematoma after ICH can activate the local microglia and cause secondary brain injury. DFA curb excessive activation of microglia and reduce neuronal death of ICH by means of clearinf away iron ions of brain tissue surrounding the hematoma, thus improve secondary neurological dysfunction. PMID- 27383489 TI - Short Communication - Determination of amino acid and free sugar contents in Korean traditional fermented soybean products of Doenjang and evaluation of their sensory attributes. AB - This study quantitatively determined contents of amino acids and free sugars in soybean fermented samples (Doenjang) using amino acid autoanalyzer and HPLC, respectively. As a result, hreonine, serine, glycine, alanine and lysine categorized as total sweet amino acids and free sugars (sucrose, maltose, glucose, galactose and fructose) were found in the range of 32.7 to 117.1 and 5.85 to 23.66mg/100 g, respectively. However, average of total sugar content was noted to be 71.63mg%. Three samples possessing the best sensory characteristics were selected for further study. The mean values of four sensory attributes such as sweet, sour, savory and bitter tastes of Doenjang samples were found to be 709.53, 210.25, 241.90 and 276.05. These findings confirm nutritive properties of fermented food products of Doenjang with improved quality and utilization. PMID- 27383490 TI - Report - Report on the heterozygosis mutations of c.567dupT, p.(Ile190Tyrfs*13) of MMACHC gene in 1 Child patient with methylmalonic academia. AB - This article reported 1 child patient with early-onset methylmalonic acidemia and proceeded gene detection for the child and his parents. The detecting results showed that there were respectively heterozygosis mutations of c.609G>A,p.(Trp203*) and c.567dupT,p.(Ile190Tyrfs*13) in the MMA CHC gene of child's parents, and all of the diseases were entailed to the child and caused the paroxysm of child. Consequently, the c.567dupT,p.(Ile190Tyrfs*13) was considered as a kind of new gene mutation. After being treated with vitamin B12 and levocamitine, the clinical symptoms and organic acid content of hematuresis of this child patient had taken a turn for the better. PMID- 27383491 TI - Report - Recurrent hip arthritis diagnosed as juvenile idiopathic arthritis: A case report. AB - Juvenile idiopathic arthritis is the most common rheumatic disease in childhood. It is a chronic inflammatory disease associated with arthritis of unknown etiology that begins before the age of 16 and persists for longer than 6 weeks. In this report, the case of a child who suffered recurrent alternative hip arthritis with bilateral hip arthritis is examined, in which he was finally diagnosed as suffering from Juvenile idiopathic arthritis. A 14-year-old boy of Taiwanese origin presented with a normal birth and developmental history. At the age of 10, right-side hip joint pain was experienced, which later migrated to the left side. On further inspection, synovium hypertrophy, cartilage erosion and hip turbid fluid accumulation were found and aseptic arthritis was presumed to be the primary cause. However, after re-examining both his clinical history and presentation, Juvenile idiopathic arthritis was the final diagnosis. Any child presenting with repeat joint swelling are at risk of Juvenile idiopathic arthritis. This is still to be the case if symptoms recede or heal and no initial diagnosis is made. Therefore, a better understanding of the risk of recurrent arthritis is needed. It cannot be emphasized strongly enough that Juvenile idiopathic arthritis should be suspected at all times when a child suffers from recurrent aseptic arthritis of the hip joint. PMID- 27383492 TI - Protective effect of heat-treated cucumber (Cucumis sativus L.) juice on alcohol detoxification in experimental rats. AB - In this study, heat-treated cucumber juice was assessed for its protective effect on blood alcohol levels and hepatic alcohol metabolic enzyme system in experimental rats. Initially, during detoxification of alcohol, all groups were orally dosed to 22% alcohol (6ml/kg body weight) along with different concentrations of heat-treated cucumber juice (10, 100 and 500mg/kg) and commercial goods for hangover-removal on sale (2ml/kg). Cucumber juice was dosed before 30 min, and simultaneously after 30min of alcohol administration, and its hepatoprotective effect on blood alcohol levels and hepatic alcohol metabolic enzyme system in experimental rats was evaluated. As a result, after 7h, remarkable reduction was found in the blood alcohol levels for all concentrations of cucumber juice treatment. Treatment with cucumber juice resulted in increasing dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) enzymatic activities in rat liver at 9h after alcohol administration thereby stimulated blood alcohol metabolism as compared with control group. The effect of heat-treated cucumber juice on alcohol detoxification was observed only in the rats treated before 30min from alcohol administration. These findings indicate that heat-treated cucumber juice has significant protective effect on alcohol detoxification in experimental rats, suggesting its usefulness in the treatment of liver injury caused by alcohol consumption. PMID- 27383493 TI - Study on stability of DMS meridian detector. AB - The stability of meridian detector was the basis to study meridian through conductance method. Ancient documents mentioned that the human body's blood could change with the time and meridians. When qi and blood came, the qi and blood would be full of that place; when qi and blood gone, the local skin shining could fade and recess. It liked the tidal fluctuation, then caused the corresponding acupuncture points conductance value changes. Modern studies had reported that meridian detector instrument the skin area of twelve meridians acupuncture points could change along with time within 24 hours. In this circumstance, whether the conductance values changes in human acupuncture points had statistical significance was vital important. DMS meridian detector instruction was adopt to measure the twelve meridian jingyuan acupuncture point in order to analyze the acupuncture point conductance value changes within one day. PMID- 27383494 TI - Analysis on the infections change and measures for the multiple drug-resistant bacteria of neurology. AB - To analyze the bacterial infection situations and the separation situations of multiple drug-resistant bacteria of the neurology of Zhengzhou People's hospital from Feb. 2012 to Dec. 2014. The patients data of neurology were retrieved by means of the doctor workstation system. The infection sites, the classification and drug-resistant feature of bacteria were classified and summarized in Excel. Finally, Compared with the infection sites, the classification and drug-resistant feature of bacteria at different year. The data obtained use SPSS 19.0 software to do statistical analysis. The infection rate of bacteria in neurology from Year 2012 to 2014 declined from 4.99% to 3.41%. But the constitution of the infection sites of bacteria had no significant changes. Staphylococcus aureus still was the majority in the infections of gram-positive bacteria, and Escherichia coli was the majority in the infections of gram-negative bacteria, and there were no significant changes in the ranking of the past three years. The separation rate of Acihetobacter baumanii and Pseudomonas aeruginosa in gram-negative bacteria gradually escalated. There were definite efficiencies in the prevention and control of the bacterial infections in neurology in the past three years. But the situation of prevention and control was still severe at the same time. PMID- 27383495 TI - Efficacy and safety of Linkus, Aminophylline diphenhydramine and acefyllin piperazine for the treatment of cough in children. AB - To evaluate the safety and efficacy of Linkus, Aminophylline with Diphenhydramine group and Acefyllin Piperazine with Diphenhydramine cough syrup on children having cough and sleep difficulty associated with cough. To determine the effects of Linkus polyherbal syrup (group A) and compared with other parallel allopathic groups (Group B and C) for cough on children and associated sleep quality and improvement. 360 children having cough inducted in 3 different groups randomly selected. Three parallel groups were the part of the study. The first study group was the herbal syrup Linkus, second group of children were taking a syrup of multinational pharmaceutical industry having Aminophylline plus Diphenhydramine however the third group received another famous brand having Acefyllin Piperazine with Diphenhydramine. Informed assent and informed consent have taken from the study subjects and their parents. Subjects with acute cough were included in the study however the subjects with chronic cough considered to be excluded. Every group of individual in the study was informed about the investigational drugs provided. Ethnic groups, frequency of cough and diseases illness (<0.05) were determine on every group on the investigational syrup. Cough impact on child and its sleep of three different syrups (every group) were assessed on day1 and day 14(p<0.001) via a likert scale. For the evaluation of pain assessment Wong baker face scale were used and level of significance in each group (p<0.001). Significant results were observed in the Linkus Group as compared to the other parallel groups including Aminophylline plus Diphenhydramine and Acefyllin Piperazine with Diphenhydramine on day 14 (p<0.001). Side effects on group B and group C (Aminophylline with Diphenhydramine and Acefyllin Piperazine with Diphenhydramine) were almost similar in number however Linkus syrup has minimum side effects on study duration. Polyherbal syrup Linkus shows better results in treatment of cough including side effects as compare to the other parallel groups B and C (Aminophylline with Diphenhydramine and Acefyllin Piperazine with Diphenhydramine). For nocturnal sleep Linkus providing better results in cough and associated problems. Pain were significantly reduce on day 14 with the herbal Linkus syrup group A (<0.001). Group B and C found less effective with more side effects as compared to Linkus syrup. Poly herbal Linkus syrup could substantially improve the clinical effect and relieves coughs and benefit lung functions and better sleep facilitation. PMID- 27383496 TI - In vitro genotoxicity of pyridine in human lymphocytes. AB - This work was carried out to study the genotoxicity of pyridine in vitro on human leucocyte culture. Cyclophosphamide, a well-known carcinogen was used as positive control. The four different concentrations of pyridine and cyclophosphamide showed breaks and pulverization of chromosomes in dose dependent manner. Higher number of pulverization was observed with higher concentration of pyridine (3.25MUg/mL). Based on this data, our results confirm that both pyridine and its precursor showed genotoxicity against human lymphocytes. PMID- 27383497 TI - Chromatographic resolution of drug analogues: 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors (statins). AB - A high performance liquid chromatographic method for the simultaneous determination both qualitative and quantitative of cholesterol lowering statin drugs in pharmaceutical formulations has been developed. The most important advantage of developed method is that all seven statin drugs can be determined on a single chromatographic system without modification in detection wavelength. An organic modifier addition (25% v/v methanol) in the presence of buffer (20mM ammonium acetate; pH 4.0 adjusted with dilute acetic acid) played a key role in the resolution of statin drugs in gradient elution with acetonitrile. The drugs were separated on a Purospher Star 4.6mm * 25cm, 5MUm, C18 column maintained at 25 degrees C with 1mLmin(-1) flow rate using ultra violet detection at 240nm. Good separation (Rs > 2.5) was achieved in a short analysis allowing simultaneous determination of all seven statins. The effect of variation in flow rate, detection wavelength and column oven temperature was also studied. The proposed method was statistically validated in terms of precision, accuracy, linearity, specificity and robustness. The newly developed method proved to be specific, robust and accurate for the quantification of seven statins in commercial pharmaceutical formulations. PMID- 27383498 TI - Effect of a real-time tele-transmission system of 12-lead electrocardiogram on the first-aid for athletes with ST-elevation myocardial infarction. AB - To study the effect of a real-time tele-transmission system of 12-lead electrocardiogram on door-to-balloon time in athletes with ST-elevation myocardial infarction. A total of 60 athletes with chest pain diagnosed as ST elevation myocardial infarction (STEMI) from our hospital were randomly divided into group A (n=35) and group B (n=25), the patients in group A transmitted the real-time tele-transmission system of 12-lead electrocardiogram to the chest pain center before arriving in hospital, however, the patients in group B not. The median door-to-balloon time was significant shorter in-group A than group B (38min vs 94 min, p<0.01) and the ratio of door-to-balloon time below 90 min was remarkable higher in-group A (94.2% vs 60%, p<0.01). The rate of catheter laboratory occupied was 5.7% in-group A and 40% in group B respectively (p=0.001). There was no statistically difference in mortality between the two groups (5.7% vs 4%, p>0.05). The median length of stay was significant reduced in group A (5 days vs 7 days, p<0.01). Real-time tele-transmission system of 12 lead electrocardiogram is beneficial to the pre-hospital diagnosis of STEMI. PMID- 27383499 TI - Clinical research on the dexmedetomidine applied for patient-controlled sedation during the lower limbs operation under combined spinal-epidural anesthesia. AB - To investigate the effect and safety of dexmedetomidine applied for patient controlled sedation under combined spinal anesthesia. 150 cases who would be implemented lower limbs operations were randomly divided into patient-controlled sedation group (Group PCS) and control group (Group C) and 75 cases for each group. The ages of patients were between 18 and 65 years old and patients were with American Society of Anesthesiologists (ASA) or level. After being implemented combined spinal anesthesia, patients of Group PCS were undergone patient-controlled sedation by using dexmedetomidine (4MUg/mL) with 2mL of load quantity, 1.5ml of background infusion quantity, 0.5mL of single dose and 20s of locking time; patients of Group C were constantly infused the normal saline at the rate of 10ml/h by pump injection. HR, MAP, SpO2, Ramsay sedation scores and airway scores before the pump injection (T0), 10 min (T1), 3 min (T2), 5 min (T3), 7min (T4) and 10min (T5) after the pump injection, at the beginning of operations (T6), 10min(T7) after the operations and in the end of operations (T8) of patients of two groups were respectively recorded. At the same time, the pressing numbers and doses of dexmedetomidine of patients of Group PCS were observed. Compared with the HR at T0, HR in Group PCS obviously decreased between T1 and T8 (P<0.05). Compared with HR in Group C, HR in Group PCS obviously slowered between T1 and T8 (P<0.05). Compared with the MAP at T0, MAP in Group PCS gradually increased between T1 and T3 and gradually reduced between T5 and T8 (P<0.05). MAP between T5 and T8 in Group PCS were significantly lower than those in Group C (P<0.05). Between T3 and T7, there were 51, 72, 74, 73, 72 patients in Group PCS whose Ramsay scores were from 3 to 4 points respectively. During the process of patient-controlled sedation of patients in Group PCS, the pressing times were 112.10+/-65. 79 times. The effective pressing numbers were 21.00+/-9. 07times. The patient-controlled dosages were (15.12+/-3.19) ml; The dosages were 11.29+/-2.16ml when the level of sedation achieved 3 to 4 scores in Ramsay sedation scores; And the required time to achieve 3 to 4 scores in Ramsay sedation scores was 7.55+/-1.53 min. In the lower limbs operations, the usage of dexmedetomidine applied for patient-controlled sedation under combined spinal anesthesia can effectively approach to the personalized medicine and is effective in clinical application. PMID- 27383501 TI - Obesity is not associated with increased morbidity in patients undergoing cytoreductive surgery with intraperitoneal chemotherapy. AB - BACKGROUND AND OBJECTIVES: Recent single-institutional series have examined the relationship of body mass index (BMI) in patients undergoing cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) generally without significant increase in serious complications with increasing BMI. This study evaluates the impact of BMI on complication rates using a national cohort. METHODS: The ACS NSQIP database was queried for patients undergoing concurrent CRS with IPC (2005-2012). Death and serious morbidity (DSM) was the primary outcome. Statistical analyses were performed to determine significant associations between peri-operative factors and DSM. RESULTS: Of 1,085 patients, there were 30.4% (n = 330) obese (BMI >30) and 32.1% (n = 348) normal weight (BMI 18.5-24.9) patients. DSM rates did not differ between these groups (P = 0.853). Obese patients were more likely to experience post-operative wound (P = 0.017) and renal (P = 0.002) complications. Hypoalbuminemia (OR 7.34; 95% CI 2.27 23.73), prolonged operative time (OR 3.02; 95% CI 1.83-4.97) and concomitant liver resection (OR 3.29; 95% CI 1.31-8.28) were independent risk factors for DSM among obese patients. CONCLUSIONS: Obesity is not significantly associated with DSM in patients undergoing CRS/IPC, and should not be a major deterrence for surgery. However, obese patients are more likely to experience wound and renal complications and hypoalbuminemia is a strong preoperative risk factor. J. Surg. Oncol. 2016;114:619-624. (c) 2016 Wiley Periodicals, Inc. PMID- 27383502 TI - Optimal high b-value for diffusion weighted MRI in diagnosing high risk prostate cancers in the peripheral zone. AB - PURPOSE: To retrospectively determine the optimal b-value(s) of diffusion weighted imaging (DWI) associated with intermediate-high risk cancer in the peripheral zone (PZ) of the prostate. MATERIALS AND METHODS: Forty-two consecutive patients underwent multi b-value (16 evenly spaced b-values between 0 and 2000 s/mm2 ) DWI along with multi-parametric MRI (MP-MRI) of the prostate at 3 Tesla followed by trans-rectal ultrasound/MRI fusion guided targeted biopsy of suspicious lesions detected at MP-MRI. Computed DWI images up to a simulated b value of 4000 s/mm2 were also obtained using a pair of b-values (b = 133 and 400 or 667 or 933 s/mm2 ) from the multi b-value DWI. The contrast ratio of average intensity of the targeted lesions and the background PZ was determined. Receiver operator characteristic curves and the area under the curve (AUCs) were obtained for separating patients eligible for active surveillance with low risk prostate cancers from intermediate-high risk prostate cancers as per the cancer of the prostate risk assessment (CAPRA) scoring system. RESULTS: The AUC first increased then decreased with the increase in b-values reaching maximum at b = 1600 s/mm2 (0.74) with no statistically significant different AUC of DWI with b-values 1067 2000 s/mm2 . The AUC of computed DWI increased then decreased with the increase in b-values reaching a maximum of 0.75 around b = 2000 s/mm2 . There was no statistically significant difference between the AUC of optimal acquired DWI and either of optimal computed DWI. CONCLUSION: The optimal b-value for acquired DWI in differentiating intermediate-high from low risk prostate cancers in the PZ is b = 1600 s/mm2 . The computed DWI has similar performance as that of acquired DWI with the optimal performance around b = 2000 s/mm2 . LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;45:125-131. PMID- 27383500 TI - Arabidopsis thaliana extracts optimized for polyphenols production as potential therapeutics for the APOE-modulated neuroinflammation characteristic of Alzheimer's disease in vitro. AB - Although the cause of Alzheimer's disease (AD) is unknown, glial-induced neuroinflammation is an early symptom. Familial AD is caused by increases in amyloid-beta (Abeta) peptide, particularly soluble oligomeric (oAbeta), considered a proximal neurotoxin and neuroinflammatory stimuli. APOE4, a naturally occurring genotype of APOE, is the greatest genetic risk factor for AD; increasing risk up to 12-fold compared to APOE3 and APOE2. oAbeta-induced neuroinflammation is greater with APOE4 compared to APOE3 and APOE2. As sinapates and flavonoids have anti-inflammatory properties, a protocol was developed for optimizing polyphenol production in seedlings of Arabidopsis thaliana (A. thaliana). Three mutants (cop1, prn1, xpf3) were identified, and the extracts treated with liver microsomes to mimic physiological metabolism, with HPLC and MS performed on the resulting metabolites for peak identification. These extracts were used to treat primary glial cells isolated from human APOE-targeted replacement (APOE-TR) and APOE-knock-out (KO) mice, with neuroinflammation induced by lipopolysaccharide (LPS) or oAbeta. The dose-response data for TNFalpha secretion demonstrate the followed the order: APOE-KO > APOE4 > APOE3 > APOE2, with xpf3 the most effective anti-neuroinflammatory across APOE genotypes. Thus, the plant-based approach described herein may be particularly valuable in treating the APOE4-induced neuroinflammatory component of AD risk. PMID- 27383503 TI - Hashimoto's Thyroiditis in South Indian Centre: Correspondence. PMID- 27383504 TI - Defining Obesity Using a Biological End Point in Sri Lankan Children. AB - OBJECTIVE: To identify the percentage of body fat mass (FM) that would define obesity among Sri Lankan children. METHODS: A cross-sectional study was conducted among 5-15 y old children in the district of Colombo. FM was assessed using Bio Impedance Assay (BIA). After a 12 h overnight fast, blood was drawn for fasting blood glucose (FBS) and lipid profile. Oral-glucose-tolerance test (OGTT) was done along with 2 h random blood sugar (RBS). Metabolic syndrome (MetS) was diagnosed by a high waist circumference (WC) with >=2 metabolic derangements [FBS/RBS, high density lipoprotein-cholesterol (HDL-C), triglyceride, and systolic and diastolic blood pressure (SBP/DBP)]. Receiver-Operator Characteristics (ROCs) were drawn to determine the best %FM that predicted MetS. RESULTS: Nine hundred twenty children were studied (547 boys). Fifteen (1.6 %) had MetS. Ninety five (10.3 %) had two and 16(1.7 %) had >=3 metabolic derangements. MetS in boys was associated with %FM of 28.6 (sensitivity 1.000; specificity 0.870) and in girls 33.7 (sensitivity 0.875; specificity 0.808). CONCLUSIONS: FM associated with adverse health outcomes in this population is comparable to other available data. A %FM of 28.6 % for boys and 33.7 % for girls would be acceptable cutoff limits. PMID- 27383505 TI - A Moveable Feast: Insects Moving at the Forest-Crop Interface Are Affected by Crop Phenology and the Amount of Forest in the Landscape. AB - Edges have become prevailing habitats, mainly as a result of habitat fragmentation and agricultural expansion. The interchange of functionally relevant organisms like insects occurs through these edges and can influence ecosystem functioning in both crop and non-crop habitats. However, very few studies have focused on the directionality of insect movement through edges, and the role of crop and non-crop amount has been ignored. Using bi-directional flight interception traps we investigated interchange of herbivore, natural enemy, pollinator and detritivore insects between native forest fragments and soybean crops, simultaneously considering movement direction, forest cover in the landscape and crop phenology. In total, 52,173 specimens and 877 morphospecies were collected. We found that, within most functional and taxonomic groups, movement intensity was similar (richness and/or abundance) between directions, whereas a predominantly forest-to-crop movement characterized natural enemies. Insect movement was extensively affected by crop phenology, decreasing during crop senescence, and was enhanced by forest cover particularly at senescence. Mainly the same herbivore species moved to and from the forest, but different natural enemy species predominated in each direction. Finally, our analyses revealed greater forest contribution to natural enemy than to herbivore communities in the crop, fading with distance to the forest in both groups. By showing that larger amounts of forest lead to richer insect interchange, in both directions and in four functional groups, our study suggests that allocation to natural and cultivated habitats at landscape level could influence functioning of both systems. Moreover, natural enemies seemed to benefit more than pests from natural vegetation, with natural enemy spillover from forests likely contributing to pest control in soybean fields. Thus consequences of insect interchange seem to be mostly positive for the agroecosystem, although consequences for the natural system deserve further study. PMID- 27383506 TI - Aliskiren and l-arginine treatments restore depressed baroreflex sensitivity and decrease oxidative stress in renovascular hypertension rats. AB - Renovascular hypertension is characterized by increased angiotensin II and oxidative stress, and by endothelial dysfunction. The purpose of this study was to test whether the administration of aliskiren (ALSK) and l-arginine (l-ARG) would restore impaired baroreflex sensitivity and reduce oxidative stress in a rat renovascular hypertension model. Hypertension was induced by clipping the left renal artery, and the following five groups were created: SHAM; two-kidney, 1-clip (2K1C); 2K1C plus ALSK (ALSK); 2K1C plus l-ARG (l-ARG); and 2K1C plus ALSK+l-ARG (ALSK+l-ARG). After 21 days of treatment, only the ALSK+l-ARG group was effective in normalizing the arterial pressure (108.8+/-2.8 mm Hg). The l-ARG and ALSK+l-ARG groups did not show hypertrophy of the left ventricle. All the treatments restored the depressed baroreflex sensitivity to values found in the SHAM group. Acute administration of TEMPOL restored the depressed baroreflex sensitivity in the 2K1C group to values that resembled those presented by the other groups. All treatments were effective for an increase in the antioxidant pathway and reduction in the oxidative pathway. In conclusion, the treatment with ALSK or l-ARG reduced oxidative stress and restored reduced baroreflex sensitivity in renovascular hypertension. In addition, the treatments were able to normalize blood pressure and reverse left ventricular hypertrophy when used in combination. PMID- 27383507 TI - Comparison of a salt check sheet with 24-h urinary salt excretion measurement in local residents. AB - The salt check sheet developed by Tsuchihashi et al. is widely used in general practice to assess salt intake and the associated diets. However, its appropriateness for the general population has not been assessed alongside 24-h urinary salt excretion monitoring. Therefore, in local residents, we analyzed the correlation between check-sheet scores and 24-h urinary salt excretion levels to determine the appropriateness of the check sheet. We asked 176 local residents to complete the salt check sheet and provide urinary samples; the latter were obtained using a proportional sampling method over a 24-h period. One hundred and forty subjects completed the study (men/women: 23/117, mean+/-s.d. age: 52.7+/ 19.6 years, blood pressure: 122.3+/-18.0/74.3+/-11.1 mm Hg), of whom 51 (36.4%) had hypertension. The total salt check-sheet scores were widely distributed (mean+/-s.d.: 11.1+/-4.2 points, range: 0-22 points), and the subjects were divided into the following groups on the basis of salt levels: 29.3% were 'low' (0-8 points), 42.8% were 'medium' (9-13 points), 23.6% were 'high' (14-19 points) and 4.3% were 'very high' (>20 points). The mean 24-h urinary salt excretion level was 8.5+/-3.3 g. The subjects with higher salt-intake levels tended to have increased 24-h urinary salt excretion levels, with significant differences between the three groups ('low' vs. 'medium' vs. 'high to very high' salt levels: 7.6+/-2.9 g vs. 8.4+/-2.8 g vs. 9.6+/-4.2 g, respectively; P=0.03). The total salt check-sheet scores significantly correlated with the 24-h urinary salt excretion levels (r=0.27; P<0.01). Thus, the salt check sheet is applicable for the general population. PMID- 27383508 TI - Associations of systolic and diastolic blood pressure night-to-day ratios with atherosclerotic cardiovascular diseases. AB - Our objective was to evaluate the associations of the systolic and diastolic blood pressure night-to-day ratios (SBP-NDR and DBP-NDR) with composite atherosclerotic cardiovascular diseases (ASCVDs) comprising coronary heart disease (CHD) and ischemic stroke (IS) cases, respectively. The clinical conditions associated with SBP-NDR and DBP-NDR were also evaluated. A total of 401 patients who underwent 24-h ambulatory BP monitoring were enrolled. In general, the mean age was 59.7+/-14.7 years and male subjects accounted for 59.1% of the study subjects. Regarding the ASCVD risk factors, 17.0% of the study subjects smoked, 5.2% abused alcohol, 2.0% had a family history of ASCVD, 23.3% had diabetes and 96.0% had dyslipidemia. Fifty (12.5%) and 128 (31.9%) study subjects had a previous diagnosis of CHD and IS, respectively. Dipper and non dipper pattern-specific differences in clinical characteristics between the SBP NDR and DBP-NDR categories were observed. The multiple linear regression analysis showed that advanced age, smoking, CHD and IS were positively associated with SBP NDR and statins were inversely associated with SBP-NDR; only IS was positively associated with DBP-NDR. The logistic regression analysis showed that after adjusting for the covariates of age, smoking, alcohol abuse, diabetes, hypertension, dyslipidemia, and SBP and DBP at admission, only DBP-NDR remained significantly associated with composite ASCVD, with an odds ratio of 1.029 (95% confidence interval 1.002-1.056, P=0.038). There were significant differences in the associations of SBP-NDR and DBP-NDR with composite ASCVD. Clinical conditions independently associated with SBP-NDR and DBP-NDR were also somewhat different. In a specific population group, DBP-NDR may be superior to SBP-NDR with respect to screening for ASCVD. PMID- 27383509 TI - Retinal microvascular diameter, a hypertension-related trait, in ECG-gated vs. non-gated images analyzed by IVAN and SIVA. AB - The diameters of the retinal microvasculature reflect intermediate target organ damage and predict adverse health outcomes. In view of the pulsatility of the cerebral blood flow and refinement of software used for off-line analysis, we assessed the repeatability of retinal microvascular diameters in ECG-gated vs. non-gated images using nonmydriatic retinal photographs (Canon Cr-DGi visualization system) postprocessed by IVAN (Vasculomatic ala Nicola, version 1.1) or SIVA (Singapore I Vessel Assessment, version 3.6). Using these algorithms, we determined the central retinal arteriolar (CRAE) and venular (CRVE) equivalents and their ratio (arteriole-to-venule ratio (AVR)). The estimates of CRAE (mean, 158.5 MUm), CRVE (222.5 MUm) and AVR (0.71) in 10 volunteers were unaffected (P?0.059) by ECG gating. We assessed intragrader repeatability by the Bland and Altman approach in 30 participants with non-gated images and 30 with ECG-gated photographs. Repeatability, which was expressed as the percentage of near maximal variability (4-s.d. range), did not improve with ECG gating. Using SIVA, CRAE and CRVE were systematically larger (P?0.031), and the AVR estimates were similar (P?0.15) compared with IVAN. The differences (IVAN SIVA) averaged -5.4 MUm for CRAE, -3.9 MUm for CRVE and -0.012 for AVR in the non gated images and -3.3 MUm, -6.9 MUm and 0.006, respectively, in the ECG-gated photographs. In conclusion, ECG gating does not affect estimates of the retinal microvascular diameters or improve intragrader repeatability. SIVA yields slightly but significantly larger estimates of the retinal arteriolar and venular diameters. Combining historical readings analyzed by IVAN with more recent readings by SIVA is possible only for AVR and is not recommended for either CRAE or CRVE. PMID- 27383510 TI - Association between social participation and hypertension among older people in Japan: the JAGES Study. AB - Hypertension is an important risk factor for cardiovascular disease, the leading cause of mortality in the world. Although previous studies have focused on individual-level behavioral risk factors associated with hypertension, there has been little research on how interacting with others, that is social participation, affects hypertension. To address this research gap, this study examined the association between social participation and hypertension in Japan, a country with a high prevalence of hypertension possibly linked to rapid population aging. Data were used from 4582 participants aged more than 65 years who participated in the Japan Gerontological Evaluation Survey (JAGES) with blood pressure data collected during a health check-up. The frequency of participation in vertical organizations (characterized by hierarchical relationships) and horizontal organizations (characterized by non-hierarchical, egalitarian relationships) was measured by a questionnaire. In a Poisson regression analysis, participation in vertical organizations was not associated with hypertension, whereas participation in horizontal organizations at least once a month was inversely associated with hypertension (prevalence ratio: 0.941). This association remained significant after adjusting for social support variables, although further adjustment for health behaviors attenuated the association. As the frequency of going out and average time spent walking were both associated with hypertension, physical activity may be a possible pathway that connects social participation and hypertension. The results of this study suggest that expanding social participation programs, especially those involving horizontal organizations, may be one way to promote better health among older people in Japan. PMID- 27383511 TI - The association between blood pressure and grip strength in adolescents: does body mass index matter? AB - Increased body mass index (BMI) has been related to both low grip strength and high blood pressure (BP) in adolescents. Previous reports of high BP associated with decreased grip strength could be due to the inherent increase in BP in youths with high BMI. This cross-sectional study aimed to examine the association between grip strength and BP in adolescents independent of BMI. A total of 88 865 Chinese adolescents aged 13-17 years were included in this study. Sex-, age- and height-specific references were applied to calculate the BP z-score and define elevated BP. Grip strength was evaluated as handgrip (kg)/weight (kg) and converted into a sex- and age-specific z-score for analysis. Using fractional polynomial regression, we found that increased BMI was associated with enhanced BP and decreased grip strength; however, after stratification by or adjustment for BMI, strong grip strength was related to an increased BP. Logistic regression models revealed that a one s.d. increase in boys' grip strength z-score was associated with an 18% (95% confidence interval: 12, 25) to 37% (19, 59) higher risk of elevated BP when adjusted for BMI. These associations remained significant after further adjustment for cardiorespiratory fitness. A similar pattern was also observed in girls. These results indicated that strong grip strength was associated with increased adolescent BP after adjustment for BMI. Our findings raise questions about using muscle-strengthening training as an approach to improve the BP profile in adolescents. PMID- 27383514 TI - Is early discharge with hospital-assisted home care really safe? PMID- 27383512 TI - Discrimination, Mental Health, and Substance Use Disorders Among Sexual Minority Populations. AB - PURPOSE: Sexual minority (lesbian, gay, bisexual) populations have a higher prevalence of mental health and substance use disorders compared to their heterosexual counterparts. Such disparities have been attributed, in part, to minority stressors, including distal stressors such as discrimination. However, few studies have examined associations between discrimination, mental health, and substance use disorders by gender among sexual minority populations. METHODS: We analyzed data from 577 adult men and women who self-identified as lesbian, gay, or bisexual and participated in Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Six questions assessed discrimination due to sexual orientation. Weighted multivariable logistic regression examined associations between experiences of sexual orientation discrimination and both mental health and substance use disorders. Analyses were conducted separately for sexual minority men and women, adjusting for sociodemographic covariates. RESULTS: Sexual minority men who ever experienced discrimination (57.4%) reported higher odds of any lifetime drug use disorder and cannabis use disorder compared to sexual minority men who never experienced discrimination. Sexual minority women who ever experienced discrimination (42.9%) reported higher odds of any lifetime mood disorder and any lifetime anxiety disorder compared to sexual minority women who never experienced discrimination. CONCLUSION: The findings suggest that discrimination is differentially associated with internalizing (mental health) and externalizing (substance use) disorders for sexual minority men and women. These findings indicate a need to consider how homophobia and heteronormative discrimination may contribute to distinct health outcomes for lesbian and bisexual women compared with gay and bisexual men. PMID- 27383515 TI - Remember fatigue during neonatal cardiopulmonary resuscitation and don't forget to change resuscitators. PMID- 27383516 TI - When should we start continuous positive airway pressure in the delivery room and how high should we go? PMID- 27383517 TI - Metronomics during palliative care in paediatric oncology? For sure! But handle me with care. PMID- 27383518 TI - Erratum. PMID- 27383519 TI - Individualised benefit-harm balance of aspirin as primary prevention measure - a good proof-of-concept, but could have been better.... AB - Guidelines from different organisations regarding the use of aspirin for primary prevention vary despite being based on similar evidence. Translating these in practice presents a further major challenge. The benefit-harm balance tool developed by Puhan et al. (BMC Med 13:250, 2015) for aspirin can overcome some of these difficulties and is therefore an important step towards personalised medicine. Although a good proof-of-concept, this tool has some important limitations that presently preclude its use in practice or for further research. One of the major benefits of aspirin that has become apparent in the last decade or so is its effect in preventing cancer and cancer-related deaths. However, this benefit is clear and consistent in randomised as well as observational evidence only for specific cancers. Additionally, it has long lag-time and carry-over periods. These nuances of aspirin's effects demand a specific and a more sophisticated model such as a time-varying model. Further refinement of this tool with respect to these aspects is merited to make it ready for evaluation in qualitative and quantitative studies with the goal of clinical utility.Please see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-015 0493-2. PMID- 27383520 TI - Classification of congenital nasal deformities: a proposal to amend the existing classification. AB - : Congenital nasal anomalies are rare malformations with a broad spectrum of defects. The only existing classification strictly relating to nasal anomalies was presented by Losee et al. (Plast Reconstr Surg 113(2):676-689, 2004). The aim of this paper is to propose some suggestions, based on our current knowledge and experience gained by treating our patients in the clinic, in creating a specification of patients with congenital nasal anomalies. All patients with congenital nose defects treated in our health center were selected for this study. The research was retrospective and included years from 1995 to 2015. Nasal anomaly associated with cleft lip and palate was excluded. Patients were classified into four categories of congenital nasal anomalies, according to Losee et al. CLASSIFICATION: In the period of 20 years, 191 patients with congenital nasal anomalies were treated in our health center. Type 1 defects were found in 124 patients, type 2 in 15, type 3 in 32 and type 4 in 20 patients. The nasal defect accompanying craniofacial syndrome is the most common type of nose malformation. The nose cleft is not always a part of craniofacial clefts; isolated forms of such malformations can occur. Vascular anomalies, due to different etiology, categorization and treatment, should not be recognized as nasal malformation. PMID- 27383522 TI - Chiral carbene-borane adducts: precursors for borenium catalysts for asymmetric FLP hydrogenations. AB - The carbene derived from (1R,3S)-camphoric acid was used to prepare the borane adduct with Piers' borane 7. Subsequent hydride abstraction gave the borenium cation 8. Adducts with 9-BBN and the corresponding (1R,3S)-camphoric acid-derived carbene bearing increasingly sterically demanding N-substituents (R = Me 9, Et 10, i-Pr 11) and the corresponding borenium cations 12-14 were also prepared. These cations were not active as catalysts in hydrogenation, although 9-11 were shown to undergo carbene ring expansion reactions at 50 degrees C to give species 15-17. The IBOX-carbene precursors 18 and 19 derived from amino alcohols (S)-valinol and (S)-tert-leucinol (R = i-Pr, t-Bu) were used to prepare borane adducts 20-23. Reaction of the carbenes 1,3-dimethylimidazol-2-ylidene (IMe), 1,3 di-iso-propylimidazol-2-ylidene (IPr) 1-benzyl-3-methylimidazol-2-ylidene (IBnMe), 1-methyl-3-phenylimidazol-2-ylidene (IPhMe) and 1-tert-butyl-3 methylimidazol-2-ylidene (ItBuMe) with diisopinocampheylborane (Ipc2BH) gave chiral adducts: (IMe)(Ipc2BH) 24, (IPr)(Ipc2BH) 25, (IBnMe)(Ipc2BH) 26, (IPhMe)(Ipc2BH) 27, and (ItBuMe)(Ipc2BH) 28. Triazolylidene-type adducts including the (10)-phenyl-9-borabicyclo [3.3.2]decane adduct of 1,3,4-triphenyl 1H-1,2,3-triazolium, rac-29 and the 9-BBN derivative of (S)-2-amino-2'-methoxy 1,1'-binaphthalene-1,2,3-triazolium 34a/b were also prepared. In catalytic studies of these systems, while several species were competent catalysts for imine reduction, in general, low enantioselectivities, ranging from 1-20% ee, were obtained. The implications for chiral borenium cation catalyst design are considered. PMID- 27383523 TI - Mechanism of Hyponatremia in Community-Acquired Pneumonia: Does B-type Natriuretic Peptide Play a Causative Role? AB - OBJECTIVE: Hyponatremia is a well-known sequela of community-acquired pneumonia (CAP). B-type natriuretic peptide (BNP) has a natriuretic effect and was found to be elevated in patients with CAP. We investigated whether BNP has a role in the pathophysiology of hyponatremia in pediatric CAP. METHODS: Serum and urine electrolytes and osmolality, as well as NT-pro-BNP (N-BNP), were obtained in 49 hospitalized pediatric patients with CAP (29 with hyponatremia, 20 with normal sodium levels. RESULTS: Urine sodium levels were lower in the hyponatremic group compared with the normonatremic group (24.3 meq/L vs 66.7 meq/L, P = 0.006). No difference in N-BNP levels was found between groups (median, 103.8 vs 100.1; P = 0.06; interquartile range, 63.7-263.3 pg/mL vs 47.4-146.4 pg/mL). N-BNP was not associated with serum or urinary sodium levels. CONCLUSIONS: These results indicate that BNP is unlikely to play a causative role in the mechanism of hyponatremia in CAP. PMID- 27383521 TI - Thyroarytenoid muscle uptake and attenuation in PET/CT in elderly. AB - The objective of this study is to compare uptake and attenuation on positron emission tomography/computed tomography (PET/CT) imaging modality at the thyroarytenoid muscle between subjects aged less and older than 65 years old. The study design is retrospective chart review. The setting is academic medical center. PET/CT images of 60 patients aged less than 65 years old and 60 patients aged more than 65 years old were selected. Demographic data were collected. Both the groups were compared with respect to the maximum standardized uptake value (SUV max) and CT attenuation of bilateral thyroarytenoid muscles. The mean SUV max of the right thyroarytenoid muscle was 2.09 +/- 0.8 in the group of patients aged less than 65 years old compared to 1.9 +/- 0.6 in the group of patients aged more than 65 years old. For the left thyroarytenoid muscle, the mean SUV max in the first and second groups was, respectively, 2 +/- 0.6 and 1.9 +/- 0.6. The differences were not statistically significant. As for the CT attenuation, the mean value at the right thyroarytenoid muscle in the first and second groups was, respectively, 31.2 +/- 0.8 HU and 20.8 +/- 14.4 HU (p < 0.05). At the left thyroarytenoid muscle, the mean value was, respectively, 29.6 +/- 9.9 and 22.8 +/ 15 (p < 0.05). This study suggests that CT attenuation measurements can be used for objectively assessing the change in the density of aging thyroarytenoid muscle. PMID- 27383524 TI - Tunicamycin aggravates endoplasmic reticulum stress and airway inflammation via PERK-ATF4-CHOP signaling in a murine model of neutrophilic asthma. AB - INTRODUCTION: Endoplasmic reticulum (ER) stress has been considered to be an important regulator of airway inflammation in the pathogenesis of bronchial asthma, but the mechanism of ER stress involved in neutrophilic asthma remain not fully understood. METHODS: Tunicamycin is a mixture of homologous nucleoside antibiotics, which is used to induce ER stress. In the present study, Tunicamycin was administered to mouse bronchial epithelial cells and a neutrophilic asthma model (OVALPS-OVA mice), and ER stress indicators and inflammatory cytokines were measured by Western blotting and Elisa. RESULTS: Tunicamycin not only induced ER stress in mouse bronchial epithelial cells, but also increased expression of inflammation indicators such as IL-6, IL-8, and TNF-alpha via PERK-ATF4-CHOP signaling. Additionally, the phosphorylation of PERK and the expression levels of ATF4 and CHOP proteins and inflammatory cytokines (IL-6, IL-8 and TNF-alpha) were elevated in the lung tissue of OVALPS-OVA mice. Administering tunicamycin further increased protein expression levels of ER stress indicators and inflammatory cytokines, and resulted in more severe asthma phenotypes in OVALPS-OVA mice, suggesting that PERK-ATF4-CHOP signaling is associated with airway inflammation in neutrophil-dominant asthma. CONCLUSIONS: These data support the emerging notion that regulation of ER stress could be strongly associated with the development of neutrophilic asthma. PMID- 27383525 TI - Macular sub-layer thinning and association with pulmonary function tests in Amyotrophic Lateral Sclerosis. AB - Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder that may have anterior visual pathway involvement. In this study, we compare the macular structure of patients with ALS to healthy controls, and examine correlations between macular sub-layer thickness measurements and pulmonary function tests and disease duration. ALS patients underwent optical coherence tomography (OCT) imaging to obtain macular cube scans of the right eye. Macular cube OCT data from age-matched healthy subjects were provided by the OCT reading center. Semi-automated retinal segmentation software was used to quantify macular sub-layers. Pulmonary function tests and time since symptom onset were collected retrospectively from the electronic medical records of ALS patients. Macular retinal nerve fiber layer was significantly thinner in ALS patients compared to healthy controls (P < 0.05). Total macular and other sub-layer thicknesses were not reduced in the ALS cohort. Macular retinal nerve fiber layer thickness positively correlated with forced vital capacity % predicted and forced expiratory volume in 1 second % predicted (P < 0.05). In conclusion, analysis of OCT measurements supports the involvement of the anterior visual pathway in ALS. Subtle structural thinning in the macular retinal nerve fiber layer correlates with pulmonary function tests. PMID- 27383527 TI - Reply: Do we still need positron emission tomography for early Alzheimer's disease diagnosis? PMID- 27383526 TI - Nanoanalytical Electron Microscopy Reveals a Sequential Mineralization Process Involving Carbonate-Containing Amorphous Precursors. AB - A direct observation and an in-depth characterization of the steps by which bone mineral nucleates and grows in the extracellular matrix during the earliest stages of maturation, using relevant biomineralization models as they grow into mature bone mineral, is an important research goal. To better understand the process of bone mineralization in the extracellular matrix, we used nanoanalytical electron microscopy techniques to examine an in vitro model of bone formation. This study demonstrates the presence of three dominant CaP structures in the mineralizing osteoblast cultures: <80 nm dense granules with a low calcium to phosphate ratio (Ca/P) and crystalline domains; calcium phosphate needles emanating from a focus: "needle-like globules" (100-300 nm in diameter) and mature mineral, both with statistically higher Ca/P compared to that of the dense granules. Many of the submicron granules and globules were interspersed around fibrillar structures containing nitrogen, which are most likely the signature of the organic phase. With high spatial resolution electron energy loss spectroscopy (EELS) mapping, spatially resolved maps were acquired showing the distribution of carbonate within each mineral structure. The carbonate was located in the middle of the granules, which suggested the nucleation of the younger mineral starts with a carbonate-containing precursor and that this precursor may act as seed for growth into larger, submicron-sized, needle-like globules of hydroxyapatite with a different stoichiometry. Application of analytical electron microscopy has important implications in deciphering both how normal bone forms and in understanding pathological mineralization. PMID- 27383528 TI - Do we still need positron emission tomography for early Alzheimer's disease diagnosis? PMID- 27383529 TI - Predicting hand function after hemidisconnection. AB - Hemidisconnections (i.e. hemispherectomies or hemispherotomies) invariably lead to contralateral hemiparesis. Many patients with a pre-existing hemiparesis, however, experience no deterioration in motor functions, and some can still grasp with their paretic hand after hemidisconnection. The scope of our study was to predict this phenomenon. Hypothesizing that preserved contralateral grasping ability after hemidisconnection can only occur in patients controlling their paretic hands via ipsilateral corticospinal projections already in the preoperative situation, we analysed the asymmetries of the brainstem (by manual magnetic resonance imaging volumetry) and of the structural connectivity of the corticospinal tracts within the brainstem (by magnetic resonance imaging diffusion tractography), assuming that marked hypoplasia or Wallerian degeneration on the lesioned side in patients who can grasp with their paretic hands indicate ipsilateral control. One hundred and two patients who underwent hemidisconnections between 0.8 and 36 years of age were included. Before the operation, contralateral hand function was normal in 3/102 patients, 47/102 patients showed hemiparetic grasping ability and 52/102 patients could not grasp with their paretic hands. After hemidisconnection, 20/102 patients showed a preserved grasping ability, and 5/102 patients began to grasp with their paretic hands only after the operation. All these 25 patients suffered from pre- or perinatal brain lesions. Thirty of 102 patients lost their grasping ability. This group included all seven patients with a post-neonatally acquired or progressive brain lesion who could grasp before the operation, and also all three patients with a preoperatively normal hand function. The remaining 52/102 patients were unable to grasp pre- and postoperatively. On magnetic resonance imaging, the patients with preserved grasping showed significantly more asymmetric brainstem volumes than the patients who lost their grasping ability. Similarly, these patients showed striking asymmetries in the structural connectivity of the corticospinal tracts. In summary, normal preoperative hand function and a post neonatally acquired or progressive lesion predict a loss of grasping ability after hemidisconnection. A postoperatively preserved grasping ability is possible in hemiparetic patients with pre- or perinatal lesions, and this is highly likely when the brainstem is asymmetric and especially when the structural connectivity of the corticospinal tracts within the brainstem is asymmetric. PMID- 27383530 TI - Analysis of risk factors and their interactions in type 2 diabetes mellitus: A cross-sectional survey in Guilin, China. AB - AIMS/INTRODUCTION: Type 2 diabetes is a metabolic disease characterized by insulin resistance, and is associated with the effects of genetic and environmental factors. The present study aimed to not only analyze the influence of a single factor for type 2 diabetes, but also to investigate the interaction effects between risk factors. MATERIALS AND METHODS: A total of 6,660 individuals selected by the method of cluster random sampling accepted a cross-sectional survey (questionnaire investigation, physical measurement, laboratory examination and liver ultrasound examination). The classification tree was used to analyze the risk factors and their interactions in type 2 diabetes. The clinical and metabolic characteristics were compared between type 2 diabetes patients and controls, and the non-conditional logistic regression model was used to quantitatively analyze the interactions. RESULTS: A total of 338 participants were classified as type 2 diabetes (217 men and 121 women), the classification tree model showed three variables with close associations with type 2 diabetes: age, triglycerides (TG) and non-alcoholic fatty liver disease (NAFLD). Type 2 diabetes patients had higher age and incidences of high TG, NAFLD, hypertension, high body mass index, high uric acid, high total cholesterol, high low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol. The multivariate logistic regression analysis showed that the following factors had interactions in type2 diabetes: high TG * advanced age (odds ratio 2.499, 95% confidence interval 1.868-3.344, P = 0.000), NAFLD * advanced age (odds ratio 1.250, 95% confidence interval 1.048-1.491, P = 0.013) and NAFLD * high TG (odds ratio 1.349, 95% confidence interval 1.144-1.590, P = 0.000). CONCLUSIONS: The present study showed that type 2 diabetes resulted from the interactions of many factors; the interactions among age, TG and NAFLD are important risk factors for type 2 diabetes. PMID- 27383531 TI - Serum BAFF levels, Methypredsinolone therapy, Epstein-Barr Virus and Mycobacterium avium subsp. paratuberculosis infection in Multiple Sclerosis patients. AB - Elevated B lymphocyte activating factor BAFF levels have been reported in multiple sclerosis (MS) patients; moreover, disease-modifying treatments (DMT) have shown to influence blood BAFF levels in MS patients, although the significance of these changes is still controversial. In addition, BAFF levels were reported increased during infectious diseases. In our study, we wanted to investigate on the serum BAFF concentrations correlated to the antibody response against Mycobacterium avium subspecies paratuberculosis (MAP), Epstein-Barr virus (EBV) and their human homologous epitopes in MS and in patients affected with other neurological diseases (OND), divided in Inflammatory Neurological Diseases (IND), Non Inflammatory Neurological Diseases (NIND) and Undetermined Neurological Diseases (UND), in comparison to healthy controls (HCs). Our results confirmed a statistically significant high BAFF levels in MS and IND patients in comparison to HCs but not NIND and UND patients. Interestingly, BAFF levels were inversely proportional to antibodies level against EBV and MAP peptides and the BAFF levels significantly decreased in MS patients after methylprednisolone therapy. These results implicate that lower circulating BAFF concentrations were present in MS patients with humoral response against MAP and EBV. In conclusion MS patients with no IgGs against EBV and MAP may support the hypothesis that elevated blood BAFF levels could be associated with a more stable disease. PMID- 27383532 TI - Lifting speed preferences and their effects on the maximal lifting capacity. AB - The objectives of this study were to evaluate how lifting capacity and subjective preferences are affected by different lifting speeds. The maximum lifting capacity of lift was determined with three independent variables, lifting speed, lifting technique, and lifting height. Questionnaires were evaluated after the experiment by the participants for the lifting speed preferences. This study found that the lifting speed was a significant factor in the lifting capacity (p<0.001); and the lifting height (p<0.001) and the interaction of lifting speed and lifting height (p=0.005) affected the lifting capacity significantly. The maximal lifting capacity was achieved around the optimal speed that was neither too fast nor too slow. Moreover, the participants' preferred lifting speeds were consistently close to the optimal lifting speed. The results showed that the common lifting practice guideline to lift slowly might make the worker unable to generate a large lifting capacity. PMID- 27383533 TI - Brain Tumors: The Influence of Tumor Type and Routine MR Imaging Characteristics at BOLD Functional MR Imaging in the Primary Motor Gyrus. AB - Purpose To evaluate the effects of histologic features and anatomic magnetic resonance (MR) imaging characteristics of brain tumors on the functional MR imaging signal in the primary motor cortex (PMC), as false-negative blood oxygen level-dependent (BOLD) functional MR imaging activation can limit the accurate localization of eloquent cortices. Materials and Methods Institutional review board approval was obtained, and informed consent was waived for this HIPAA compliant retrospective study. It comprised 63 patients referred between 2006 and 2014 for preoperative functional MR imaging localization of the Rolandic cortex. The patients had glioblastoma multiforme (GBM) (n = 20), metastasis (n = 21), or meningioma (n = 22). The volumes of functional MR imaging activation were measured during performance of a bilateral hand motor task. Ratios of functional MR imaging activation were normalized to PMC volume. Statistical analysis was performed for the following: (a) differences between hemispheres within each histologic tumor type (paired Wilcoxon test), (b) differences across tumor types (Kruskal-Wallis and Fisher tests), (c) pairwise tests between tumor types (Mann Whitney U test), (d) relationships between fast fluid-attenuated inversion recovery (FLAIR) data and enhancement volume with activation (Spearman rank correlation coefficient), and (e) differences in activation volumes by tumor location (Mann-Whitney U test). Results A significant interhemispheric difference was found between the activation volumes in GBMs (mean, 511.43 voxels +/- 307.73 [standard deviation] and 330.78 voxels +/- 278.95; P < .01) but not in metastases (504.68 voxels +/- 220.98 and 460.22 voxels +/- 276.83; P = .15) or meningiomas (424.07 voxels +/- 247.58 and 415.18 voxels +/- 222.36; P = .85). GBMs showed significantly lower activation ratios (median, 0.49; range, 0.04-1.15) than metastases (median, 0.79; range, 0.28-1.66; P = .043) and meningiomas (median, 0.91; range, 0.52-2.05; P < .01). There was a moderate correlation with the volumes of FLAIR abnormality in metastases (rho = -0.50) and meningiomas (rho = 0.55). Enhancement volume (rho = -0.11) and tumor distance from the PMC (median, 0.73 and range, 0.04-2.05 for near and median, 0.82 and range, 0.39-1.66 for far; P = .14) did not influence activation. Conclusion BOLD functional MR imaging activation in the ipsilateral PMC is influenced by tumor type and is significantly reduced in GBMs. FLAIR abnormality correlates moderately with the activation ratios in metastases and meningiomas. (c) RSNA, 2016 Online supplemental material is available for this article. PMID- 27383534 TI - Pneumonia and influenza hospitalizations among children under 5 years of age in Suzhou, China, 2005-2011. AB - BACKGROUND: The disease burden of influenza among children in China has not been well described. OBJECTIVE: To estimate the influenza-associated excess hospitalization rate and compare the hospitalization length and costs between pneumonia and influenza (P&I) and other community-acquired diseases (CAD) in Suzhou, China. METHODS: We retrospectively collected hospital discharge data on pediatric patients' discharge diagnosis, hospital costs, and length of hospital stay in Suzhou. P&I hospitalization was defined as a primary discharge diagnosis of pneumonia and influenza disease (ICD-10 codes J09-J18). Other CAD were common community-acquired diseases among children. Negative binomial regression models were used to estimate the weekly P&I hospitalizations in Suzhou. Excess P&I hospitalizations due to influenza were calculated as the difference in P&I hospitalizations between the epidemic period and the baseline period. Baseline was defined as when the influenza-positive rates were <5% for two consecutive weeks. RESULTS: From October 2005 to September 2011, we identified a total of 180 091 all-cause hospitalizations among children <5 years of age in Suzhou City. The rates of P&I and influenza-associated excess hospitalizations were highest in the 2009-2010 pandemic and 2010-2011 post-pandemic seasons. Infants <6 months of age had the highest P&I hospitalization rates, the longest hospital stays (7.5-8.0 days), and the highest hospitalization costs for P&I. Compared with other CAD, children admitted for P&I had longer hospital stays and higher hospitalization costs. CONCLUSIONS: The influenza-associated P&I hospitalization rates and economic burden were high among children. Targeted influenza prevention and control strategies for young children in Suzhou may reduce the influenza associated hospitalizations in this age group. PMID- 27383535 TI - FastRNABindR: Fast and Accurate Prediction of Protein-RNA Interface Residues. AB - A wide range of biological processes, including regulation of gene expression, protein synthesis, and replication and assembly of many viruses are mediated by RNA-protein interactions. However, experimental determination of the structures of protein-RNA complexes is expensive and technically challenging. Hence, a number of computational tools have been developed for predicting protein-RNA interfaces. Some of the state-of-the-art protein-RNA interface predictors rely on position-specific scoring matrix (PSSM)-based encoding of the protein sequences. The computational efforts needed for generating PSSMs severely limits the practical utility of protein-RNA interface prediction servers. In this work, we experiment with two approaches, random sampling and sequence similarity reduction, for extracting a representative reference database of protein sequences from more than 50 million protein sequences in UniRef100. Our results suggest that random sampled databases produce better PSSM profiles (in terms of the number of hits used to generate the profile and the distance of the generated profile to the corresponding profile generated using the entire UniRef100 data as well as the accuracy of the machine learning classifier trained using these profiles). Based on our results, we developed FastRNABindR, an improved version of RNABindR for predicting protein-RNA interface residues using PSSM profiles generated using 1% of the UniRef100 sequences sampled uniformly at random. To the best of our knowledge, FastRNABindR is the only protein-RNA interface residue prediction online server that requires generation of PSSM profiles for query sequences and accepts hundreds of protein sequences per submission. Our approach for determining the optimal BLAST database for a protein-RNA interface residue classification task has the potential of substantially speeding up, and hence increasing the practical utility of, other amino acid sequence based predictors of protein-protein and protein-DNA interfaces. PMID- 27383536 TI - MicroRNA-125b Suppresses Ovarian Cancer Progression via Suppression of the Epithelial-Mesenchymal Transition Pathway by Targeting the SET Protein. AB - BACKGROUND/AIMS: MicroRNA-125b (miR-125b) is overexpressed in several types of cancer and contributes to chemotherapy resistance. However, its role in epithelial ovarian carcinoma remains unknown. The goal of this study was to identify the relationship between miR-125b and the epithelial-mesenchymal transition (EMT) in ovarian cancer. METHODS: In total, 55patients with epithelial ovarian cancer (EOC) were included in our study. The relative expression of miR 125b was measured using real-time polymerase chain reaction (RT-PCR).The protein expression of SET and EMT-related indicators in cell lines were assessed by Western blot. The regulation of SET by miR-125b was confirmed using luciferase reporter assays. The effect of miR-125b on metastasis was evaluated using an in vivo metastasis model. RESULTS: miR-125b expression was markedly lower in the EOC specimens. Ectopic expression of miR-125b in EOC cells significantly inhibited tumor invasion.miR-125b expression was negatively associated with both EMT and SET expression, in vivo and in vitro. Mechanistic studies identified SET as a direct target of miR-125b, and the downregulation of SET, observed during tumor migration, was affected by the overexpression of miR125b. CONCLUSION: miR-125b suppresses EOC cell migration and invasion by targeting the SET protein, and this study may provide a novel mechanism for understanding the progression of EOC. PMID- 27383537 TI - miR-106a-5p Suppresses the Proliferation, Migration, and Invasion of Osteosarcoma Cells by Targeting HMGA2. AB - We aim to investigate the effect of miR-106a-5p on the proliferation, migration, and invasion of osteosarcoma (OS) cells by targeting high-mobility group AT-hook 2 (HMGA2). Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was used for detecting the expressions of miR-106-5p and HMGA2 in 137 OS and adjacent normal bone tissues. Immunohistochemistry was applied for the HMGA2 protein expression detection. Luciferase reporter gene assay was conducted for verifying whether miR-106-5p targeted HMGA2. MG63 and U2SO cells were respectively divided into five groups: Blank, miR-106a-5p, scramble, HMGA2-siRNA, and miR-106a-5p+HMGA2 groups. RT-qPCR and western blot were applied for detecting the expressions of miR-106a-5p and HMGA2 in five groups. Proliferation rate, cell cycle, invasion, and migration ability of OS cells were detected using methyl thiazolyl-tetrazolium, 5-ethynyl-2'-deoxyuridine (Edu) assay, flow cytometry, and Transwell. Compared with adjacent normal tissues, OS tissues presented with decreased miR-106a-5p expressions, elevated HMGA2 mRNA, and positive expressions (all p < 0.05). The sensitivity and specificity of miR-106a-5p were 97.8%, 93.43%, and HMGA2 mRNA were 97.8%, 99.27%, separately. miR-106a-5p and HMGA2 expressions were associated with tumor size, Enneking stage, distant metastasis, and lung metastasis. Expressions of HMGA2 in OS cells in miR-106a-5p and HMGA2 siRNA groups were both significantly decreased with the same downregulation level, and the proliferation rates in both groups were obviously slowed down after 48 h (both p < 0.001). Edu positive cells, S phase cells (majority of cells blocked at G0/G1 phase), migratory and invasive cells were obviously decreased (all p < 0.05). Downregulation of miR-106a-5p was found in OS tissues, and upregulation of miR-106a-5p can inhibit the proliferation, migration, and invasion by targeting HMGA2 in OS cells. PMID- 27383538 TI - Reconstruction of Hypopharyngeal and Esophageal Defects Using a Gastric Tube after Total Esophagectomy and Pharyngolaryngectomy. AB - AIM: This study investigated the value of gastric tube during surgery for advanced hypopharyngeal and cervical esophageal cancer. METHOD: From November 2007 to December 2012, 42 patients underwent total pharyngo-laryngo-esophagectomy because of advanced hypopharyngeal or cervical esophageal cancer and were reconstructed with a gastric tube. Clinical swallowing function, morbidity, overall survival, and progression-free survival were evaluated postoperatively. RESULT: There were no severe complications, including no gastric necrosis, surgery-related postoperative morbidity, hemothorax, thoracostomach, or severe reflux esophagitis. Anastomotic leakage occurred in 2 cases, and these patients healed spontaneously with conservative management. Pulmonary infection developed in 5 patients. Anastomotic stenosis occurred in 2 cases and was managed with endoscopic dilatation. Regurgitation during the night was observed in 5 cases and was controlled by medication. All the patients regained their swallowing ability and thereby increased their quality of life. All patients were followed for 30-60 months; 2 of them were lost 6 months after surgery. The 3-year overall and progression-free survival rates were 58.1 and 56.2% respectively, and the 5-year overall and progression-free survival rates were 27.6 and 21.8%, respectively. CONCLUSION: Reconstruction by gastric tube is a dependable one-stage procedure that restores gastrointestinal continuity after total pharyngo-laryngo esophagectomy. PMID- 27383539 TI - Insulin resistance is associated with digital ulcer in patients with systemic sclerosis. AB - OBJECTIVES: To investigate the relationship between insulin resistance and digital ulcers (DUs) in patients with systemic sclerosis (SSc). METHODS: Using a cross-sectional design, we recruited 73 consecutive female patients with SSc and 109 sex- and age-matched healthy controls in South Korea from July 2014 to June 2015. The magnitude of insulin resistance was measured using the homeostatic model assessment of insulin resistance (HOMA-IR). DUs ever included active and healed DUs and the extent of skin fibrosis was evaluated using the modified Rodnan skin score (MRSS). RESULTS: The HOMA-IR in patients with SSc was significantly higher than that in healthy controls (median 1.18 vs. 0.71, p<0.001). In SSc patients, 7 (9.6%) had active DUs and 14 subjects (19.2%) had healed DUs; thus, DUs ever were observed in 21 cases (28.8%). SSc patients with DUs ever had significantly higher HOMA-IR and MRSS compared with those without this feature (median, 2.05 vs. 0.99, p=0.001 and 14 vs. 9.5, p=0.011, respectively). After adjustment for confounding factors using multivariable logistic regression analyses, the HOMA-IR showed a significant positive association with the presence of DUs ever in patients with SSc (OR=1.43, 95% CI=1.01-2.05, p=0.048). In addition, higher MRSS was significantly correlated with DUs ever (OR=1.11, 95% CI=1.02-1.21, p=0.015). CONCLUSIONS: Insulin resistance was independently associated with the presence of DUs in patients with SSc and may be a potential biomarker for SSc micro-vasculopathy. Moreover, our data also suggest a potential contribution of insulin resistance to the pathogenesis of DUs. PMID- 27383540 TI - A Bayesian multivariate joint frailty model for disease recurrences and survival. AB - Motivated by a study for soft tissue sarcoma, this article considers the analysis of diseases recurrence and survival. A multivariate frailty hazard model is established for joint modeling of three correlated time-to-event outcomes: local disease recurrence, distant disease recurrence (metastasis), and death. The goals are to find out (i) the effects of treatments on local and distant disease recurrences, and death, (ii) the effects of local and distant disease recurrences on death, and (iii) the correlation between local and distant recurrences. By our approach, all these three important questions, which are commonly asked in similar medical research studies, can be answered by a single model. We put the proposed joint frailty model in a Bayesian framework and use a hybrid Monte Carlo algorithm for the computation of posterior distributions. This hybrid algorithm relies on the evaluation of the gradient of target log density and a guided walk progress, and it combines these two strategies to suppress random walk behavior. A further distinction is that the hybrid algorithm can update all the components of a multivariate state vector simultaneously. Simulation studies are conducted to assess the proposed joint frailty model and the computation algorithm. The motivating soft tissue sarcoma data set is analyzed for illustration purpose. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27383541 TI - Adult CHD: the ongoing need for physician counselling about heredity and contraceptive options. AB - : Purpose Current guidelines recommend that patients with CHD receive age appropriate counselling on reproduction, pregnancy, and risk of heredity. Our aim was to examine patient knowledge of reproductive health and explore the association between patient knowledge of CHD transmission risk and earlier physician counselling in adults with CHD. METHODS: We performed a cross-sectional survey of patients with CHD aged 18 years and older in a paediatric hospital. RESULTS: Of the 100 patients who completed the questionnaire, most did not report counselling on heredity (66%) or contraception (71%). Of the 54 women, 25 (46%) identified their contraceptive options correctly; 42 (78%) women were classified as being at significantly increased risk for an adverse outcome during pregnancy, and of these 20 (48%) identified this risk correctly. Of all patients surveyed, 72% did not know that having CHD placed them at increased risk for having a child with CHD. On multivariate analysis, factors associated with correct knowledge about risk of recurrence were correct identification of CHD diagnosis (p=0.04) and patient-reported counselling (p=0.001). CONCLUSIONS: Knowledge about heredity, pregnancy risk, and contraceptive options is inadequate among adults with CHD followed-up in a paediatric subspecialty clinic. The majority of patients did not report a history of counselling about reproductive health. There is a strong correlation between history of counselling by the patient's cardiologist and correct knowledge about recurrence risk, suggesting that effective reproductive counselling can positively impact this knowledge gap. PMID- 27383542 TI - Laboratory-Evolved Enzymes Provide Snapshots of the Development of Enantioconvergence in Enzyme-Catalyzed Epoxide Hydrolysis. AB - Engineered enzyme variants of potato epoxide hydrolase (StEH1) display varying degrees of enrichment of (2R)-3-phenylpropane-1,2-diol from racemic benzyloxirane. Curiously, the observed increase in the enantiomeric excess of the (R)-diol is not only a consequence of changes in enantioselectivity for the preferred epoxide enantiomer, but also to changes in the regioselectivity of the epoxide ring opening of (S)-benzyloxirane. In order to probe the structural origin of these differences in substrate selectivity and catalytic regiopreference, we solved the crystal structures for the evolved StEH1 variants. We used these structures as a starting point for molecular docking studies of the epoxide enantiomers into the respective active sites. Interestingly, despite the simplicity of our docking analysis, the apparent preferred binding modes appear to rationalize the experimentally determined regioselectivities. The analysis also identifies an active site residue (F33) as a potentially important interaction partner, a role that could explain the high conservation of this residue during evolution. Overall, our experimental, structural, and computational studies provide snapshots into the evolution of enantioconvergence in StEH1-catalyzed epoxide hydrolysis. PMID- 27383543 TI - Pathology Informatics Essentials for Residents: A Flexible Informatics Curriculum Linked to Accreditation Council for Graduate Medical Education Milestones. AB - CONTEXT: -Recognition of the importance of informatics to the practice of pathology has surged. Training residents in pathology informatics has been a daunting task for most residency programs in the United States because faculty often lacks experience and training resources. Nevertheless, developing resident competence in informatics is essential for the future of pathology as a specialty. OBJECTIVE: -To develop and deliver a pathology informatics curriculum and instructional framework that guides pathology residency programs in training residents in critical pathology informatics knowledge and skills, and meets Accreditation Council for Graduate Medical Education Informatics Milestones. DESIGN: -The College of American Pathologists, Association of Pathology Chairs, and Association for Pathology Informatics formed a partnership and expert work group to identify critical pathology informatics training outcomes and to create a highly adaptable curriculum and instructional approach, supported by a multiyear change management strategy. RESULTS: -Pathology Informatics Essentials for Residents (PIER) is a rigorous approach for educating all pathology residents in important pathology informatics knowledge and skills. PIER includes an instructional resource guide and toolkit for incorporating informatics training into residency programs that vary in needs, size, settings, and resources. PIER is available at http://www.apcprods.org/PIER (accessed April 6, 2016). CONCLUSIONS: -PIER is an important contribution to informatics training in pathology residency programs. PIER introduces pathology trainees to broadly useful informatics concepts and tools that are relevant to practice. PIER provides residency program directors with a means to implement a standardized informatics training curriculum, to adapt the approach to local program needs, and to evaluate resident performance and progress over time. PMID- 27383544 TI - Sjogren syndrome. PMID- 27383545 TI - Mitochondrial dynamics altered by oxidative stress in cancer. AB - Mitochondria as crucial organelles regulate cellular energy generation, calcium and redox homeostasis, and apoptosis. To perform the cellular functions effectively, mitochondria continuously change their structure and morphology through protein machineries controlling fission and fusion process (mitochondrial dynamics). Traditionally, many researches had focused on the interaction of mitochondrial dynamics and apoptosis. However, recent studies are reporting the alteration of mitochondrial dynamics in human diseases including many types of cancers. Considering that cancers maintain a high level of reactive oxygen species (ROS), mitochondrial dynamics can be influenced by oxidative stress. In this review, we will discuss the alteration of mitochondrial dynamics by ROS and its effect on metastasis and chemoresistance in cancers. PMID- 27383556 TI - Synthesis, Crystal Analyses, Physical Properties, and Electroluminescent Behavior of Unsymmetrical Heterotwistacenes. AB - Four novel unsymmetrical heteroacenes containing five-membered heterocycles (OPyN, TPyN, TPyC, TPyO) have been synthesized and characterized. The formed molecules exhibited twisted structures, determined by crystal analysis and showed blue/green fluorescence in dichloromethane and in thin film. Compounds OPyN and TPyN were selectively used as active ingredients, and the fabricated devices displayed promising electroluminescent performance. PMID- 27383557 TI - Diverse approaches to the health economic evaluation of bariatric surgery: a comprehensive systematic review. AB - BACKGROUND: Health economic evaluations inform healthcare resource allocation decisions for treatment options for obesity including bariatric/metabolic surgery. As an important advance on existing systematic reviews, we aimed to capture, summarize and synthesize a diverse range of economic evaluations on bariatric surgery. METHODS: Studies were identified by electronic screening of all major biomedical/economic databases. Studies included if they reported any quantified health economic cost and/or consequence with a measure of effect for any type of bariatric surgery from 1995 to September 2015. Study screening, data extraction and synthesis followed international guidelines for systematic reviews. RESULTS: Six thousand one hundred eighty-seven studies were initially identified. After two levels of screening, 77 studies representing 17 countries (56% USA) were included. Despite study heterogeneity, common themes emerged, and important gaps were identified. Most studies adopted the healthcare system/third party payer perspective; reported costs were generally healthcare resource use (inpatient/shorter-term outpatient). Out-of-pocket costs to individuals, family members (travel time, caregiving) and indirect costs due to lost productivity were largely ignored. Costs due to reoperations/complications were not included in one-third of studies. Body-contouring surgery included in only 14%. One study evaluated long-term waitlisted patients. Surgery was cost-effective/cost-saving for severely obese with type 2 diabetes mellitus. Study quality was inconsistent. DISCUSSION: There is a need for studies that assume a broader societal perspective (including out-of-pocket costs, costs to family and productivity losses) and longer-term costs (capture reoperations/complications, waiting, body contouring), and consequences (health-related quality-of-life). Full economic evaluation underpinned by reporting standards should inform prioritization of patients (e.g. type 2 diabetes mellitus with body mass index 30 to 34.9 kg/m(2) or long-term waitlisted) for surgery. (c) 2016 World Obesity. PMID- 27383559 TI - Catalytic asymmetric total synthesis of (+)-artalbic acid. AB - The first total synthesis of (+)-artalbic acid has been accomplished using asymmetric allylation of an acetoacetate derivative with a phase-transfer catalyst. This synthetic work was completed in 12 steps from isopropyl acetoacetate with high stereocontrol. In addition, the absolute configuration of naturally occurring artalbic acid was determined to be 7S, 9S, and 10S. PMID- 27383560 TI - Biocatalysis and Biomass Conversion in Alternative Reaction Media. AB - In this Minireview, the state of the art in the use of ionic liquids (ILs) and deep eutectic solvents (DESs) as alternative reaction media for biocatalytic processes and biomass conversion is presented. Initial, proof-of-concept studies, more than a decade ago, involved first-generation ILs based on dialkylimidazolium cations and non-coordinating anions, such as tetrafluoroborate and hexafluorophosphate. More recently, emphasis has switched to more environmentally acceptable second-generation ILs comprising cations, which are designed to be compatible with enzymes and, in many cases are derived from readily available, renewable resources, such as cholinium salts. Protic ionic liquids (PILs), prepared simply by mixing inexpensive amines and acids, are particularly attractive from both an environmental and economic viewpoint. DESs, prepared by mixing inexpensive salts with, preferably renewable, hydrogen-bond donors such as glycerol and amino acids, have also proved suitable reaction media for biocatalytic conversions. A broad range of enzymes can be used in ILs, PILs and DESs, for example lipases in biodiesel production. These neoteric solvents are of particular interest, however, as reaction media for biocatalytic conversions of substrates that have limited solubility in common organic solvents, such as carbohydrates, nucleosides, steroids and polysaccharides. This has culminated in the recent focus of attention on their use as (co)solvents in the pretreatment and saccharification of lignocellulose as the initial steps in the conversion of second-generation renewable biomass into biofuels and chemicals. They can similarly be used as reaction media in subsequent conversions of hexoses and pentoses into platform chemicals. PMID- 27383558 TI - Appropriate targeting of artemisinin-based combination therapy by community health workers using malaria rapid diagnostic tests: findings from randomized trials in two contrasting areas of high and low malaria transmission in south western Uganda. AB - OBJECTIVE: To compare the impact of malaria rapid diagnostic tests (mRDTs), used by community health workers (CHWs), on the proportion of children <5 years of age receiving appropriately targeted treatment with artemisinin-based combination therapy (ACT), vs. presumptive treatment. METHODS: Cluster-randomized trials were conducted in two contrasting areas of moderate-to-high and low malaria transmission in rural Uganda. Each trial examined the effectiveness of mRDTs in the management of malaria and targeting of ACTs by CHWs comparing two diagnostic approaches: (i) presumptive clinical diagnosis of malaria [control arm] and (ii) confirmatory diagnosis with mRDTs followed by ACT treatment for positive patients [intervention arm], with village as the unit of randomisation. Treatment decisions by CHWs were validated by microscopy on a reference blood slide collected at the time of consultation, to compare the proportion of children <5 years receiving appropriately targeted ACT treatment, defined as patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving artemether-lumefantrine or rectal artesunate, and patients with no malaria parasites not given ACT. RESULTS: In the moderate-to-high transmission area, ACT treatment was appropriately targeted in 79.3% (520/656) of children seen by CHWs using mRDTs to diagnose malaria, vs. 30.8% (215/699) of children seen by CHWs using presumptive diagnosis (P < 0.001). In the low transmission area, 90.1% (363/403) children seen by CHWs using mRDTs received appropriately targeted ACT treatment vs. 7.8% (64/817) seen by CHWs using presumptive diagnosis (P < 0.001). Low mRDT sensitivity in children with low-density parasitaemia (<200 parasites/MUl) was identified as a potential concern. CONCLUSION: When equipped with mRDTs, ACT treatments delivered by CHWs are more accurately targeted to children with malaria parasites. mRDT use could play an important role in reducing overdiagnosis of malaria and improving fever case management within iCCM, in both moderate-to-high and low transmission areas. Nonetheless, missed treatments due to the low sensitivity of current mRDTs in patients with low parasite density are a concern. For community-based treatment in areas of low transmission and/or non-immune populations, presumptive treatment of all fevers as malaria may be advisable, until more sensitive diagnostic assays, suitable for routine use by CHWs in remote settings, become available. PMID- 27383561 TI - Dual Strong Couplings Between TPPS J-Aggregates and Aluminum Plasmonic States. AB - We report on the spectral properties of strong coupling between the localized surface plasmon resonances (LSPRs) of aluminum (Al) nanostructures and tetraphenylporphyrin tetrasulfonic acid hydrate (TPPS) J-aggregates. Because of their wide spectral range of LSPR bands from ultraviolet to near-infrared wavelengths by controlling structural size, Al nanodisks can realize strong coupling with different excitons of TPPS J-aggregates. The Rabi splitting energies of the excitons based on Soret and Q bands are 300 and 180 meV, respectively. In addition to extinction spectrum, we have also measured an excitation spectrum to determine the essential absorption of the hybrid states and successfully confirmed a shoulder peak corresponding to a lower branch of hybrid states. In Al nanorod systems, strong coupling with two excitons can also be selectively induced by merely rotating the polarization of the incident light, which constituted a simple platform for the dynamic control of exciton/plasmon coupling states. PMID- 27383562 TI - Workplace bullying among nurses and their related factors in Japan: a cross sectional survey. AB - AIMS AND OBJECTIVES: To explore the association between workplace bullying and workplace environment factors among nurses in Japan. BACKGROUND: Workplace bullying among nurses is increasing globally and occurs more frequently than among other professions. However, there is little information on the impact of workplace environment factors on nurse bullying in Japan. DESIGN: A cross sectional survey using a self-administered questionnaire. METHODS: Participants were 1152 nurses recruited at seminars or training courses outside of their workplaces in Tokyo. Workplace bullying was measured using the Negative Acts Questionnaire-Revised. Participants were considered to have been 'bullied' if they reported experiencing at least one negative act on a daily or weekly basis. Workplace environment factors were measured using the Practice Environment Scale of the Nursing Work Index, which comprises five domains: nurse participation in hospital affairs; nursing foundations for quality of care; nurse manager ability, leadership and support of nurses; staffing and resource adequacy; and collegial nurse-physician relationships. RESULTS: A total of 898 (78.0%) questionnaires were returned, of which 825 (71.6%) were analysed. Altogether, 153 (18.5%) nurses were considered 'bullied.' The three most frequent negative acts reported as occurring on a weekly or daily basis were 'someone withholding information which affects your performance' (6.7%), 'being exposed to an unmanageable workload' (4.4%) and 'being shouted at or being the target of spontaneous anger (or rage)' (3.6%). Logistic regression analysis indicated that 'bullied' were associated with low scores on two work environment domains: nurse manager ability, leadership and support of nurses and staffing and resource adequacy. CONCLUSIONS: Effective nurse manager leadership and support as well as appropriate staffing management may positively influence workplace bullying among nurses in Japan. Authentic leadership styles and allowing nurses to easily request days off might also be important. RELEVANCE TO CLINICAL PRACTICE: Nurse managers' leadership may influence nurses' workplace bullying. PMID- 27383563 TI - Spontaneous coronary artery dissection and healing documented by optical coherence tomography. PMID- 27383566 TI - A gas-diffusion microfluidic paper-based analytical device (MUPAD) coupled with portable surface-enhanced Raman scattering (SERS): facile determination of sulphite in wines. AB - A novel facile method for on-site determination of sulphite in wine using a gas diffusion microfluidic paper-based analytical device (MUPAD) combined with surface-enhanced Raman spectroscopy (SERS) was explored. The inexpensive and disposable MUPAD was realized by sandwiching the ZnO-paper disc and integrating gas-diffusion separation and gas preconcentration on a paper-based platform. Through extensive condition optimization, the SERS signal at a shift of 620 cm( 1) and the concentration of SO2 showed good linearity in the range of 5-300 MUg mL(-1). The linear correlation coefficient was 0.995 and the detection limit for sulphite was found to be 2 MUg mL(-1). Ultimately, this proposed method was applied to the determination of sulphite in wine, which can be essentially paralleled with the official method. Endowed with portability, minimal reagent consumption, and operational simplicity, this developed device would find broad utilization for on-site monitoring of sulphite. PMID- 27383565 TI - A twist of fate: How a meiotic protein is providing new perspectives on germ cell development. AB - The molecular pathways that govern how germ line fate is acquired is an area of intense investigation that has major implications for the development of assisted reproductive technologies, infertility interventions, and treatment of germ cell cancers. Transcriptional repression has emerged as a primary mechanism to ensure suppression of somatic growth programs in primordial germ cells. In this commentary, we address how xnd-1 illuminates our understanding of transcriptional repression and how it is coordinated with the germ cell differentiation program. We recently identified xnd-1 as a novel, early determinant of germ cell fates in Caenorhabditis elegans. Our study revealed that XND-1 is maternally deposited into early embryos where it is selectively enriched in the germ lineage and then exclusively found on chromatin in the germ lineage throughout development and into adulthood when it dissociates from chromosomes in late pachytene. This localization is consistent with a range of interesting germ cell defects that suggest xnd-1 is a pivotal determinant of germ cell characteristics. Loss of xnd 1 results in a unique "one PGC (primordial germ cell)" phenotype due to G2 cell cycle arrest of the germline precursor blastomere, P4, which predisposes the animal and its progeny for reduced fecundity. The sterility in xnd-1 mutants is correlated with an increase in the transcriptional activation-associated histone modification, dimethylation of histone H3 lysine 4 (H3K4me2), and aberrant expression of somatic transgenes but overlapping roles with nos-2 and nos-1 suggest that transcriptional repression is achieved by multiple redundant mechanisms. PMID- 27383564 TI - TRPC6 channel activation promotes neonatal glomerular mesangial cell apoptosis via calcineurin/NFAT and FasL/Fas signaling pathways. AB - Glomerular mesangial cell (GMC) proliferation and death are involved in the pathogenesis of glomerular disorders. The mechanisms that control GMC survival are poorly understood, but may include signal transduction pathways that are modulated by changes in intracellular Ca(2+) ([Ca(2+)]i) concentration. In this study, we investigated whether activation of the canonical transient receptor potential (TRPC) 6 channels and successive [Ca(2+)]i elevation alter neonatal GMC survival. Hyperforin (HF)-induced TRPC6 channel activation increased [Ca(2+)]i concentration, inhibited proliferation, and triggered apoptotic cell death in primary neonatal pig GMCs. HF-induced neonatal GMC apoptosis was not associated with oxidative stress. However, HF-induced TRPC6 channel activation stimulated nuclear translocation of the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1). HF also increased cell death surface receptor Fas ligand (FasL) level and caspase-8 activity in the cells; effects mitigated by [Ca(2+)]i chelator BAPTA, calcineurin/NFAT inhibitor VIVIT, and TRPC6 channel knockdown. Accordingly, HF-induced neonatal GMC apoptosis was attenuated by BAPTA, VIVIT, Fas blocking antibody, and a caspase-3/7 inhibitor. These findings suggest that TRPC6 channel-dependent [Ca(2+)]i elevation and the ensuing induction of the calcineurin/NFAT, FasL/Fas, and caspase signaling cascades promote neonatal pig GMC apoptosis. PMID- 27383567 TI - Adapting DFT+U for the Chemically Motivated Correction of Minimal Basis Set Incompleteness. AB - Recent algorithmic and hardware advances have enabled the application of electronic structure methods to the study of large-scale systems such as proteins with O(10(3)) atoms. Most such methods benefit greatly from the use of reduced basis sets to further enhance their speed, but truly minimal basis sets are well known to suffer from incompleteness error that gives rise to incorrect descriptions of chemical bonding, preventing minimal basis set use in production calculations. We present a strategy for improving these well-known shortcomings in minimal basis sets by selectively tuning the energetics and bonding of nitrogen and oxygen atoms within proteins and small molecules to reproduce polarized double-zeta basis set geometries at minimal basis set cost. We borrow the well-known +U correction from the density functional theory community normally employed for self-interaction errors and demonstrate its power in the context of correcting basis set incompleteness within a formally self-interaction free Hartree-Fock framework. We tune the Hubbard U parameters for nitrogen and oxygen atoms on small-molecule tautomers (e.g., cytosine), demonstrate the applicability of the approach on a number of amide-containing molecules (e.g., formamide, alanine tripeptide), and test our strategy on a 10 protein test set where anomalous proton transfer events are reduced by 90% from RHF/STO-3G to RHF/STO-3G+U, bringing the latter into quantitative agreement with RHF/6-31G* results. Although developed with the study of biological molecules in mind, this empirically tuned U approach shows promise as an alternative strategy for correction of basis set incompleteness errors. PMID- 27383568 TI - Outcome and Learning Curve in 159 Consecutive Patients Undergoing Total Laparoscopic Hemihepatectomy. AB - Importance: Widespread implementation of laparoscopic hemihepatectomy is currently limited by its technical difficulty, paucity of training opportunities, and perceived long and harmful learning curve. Studies confirming the possibility of a short and safe learning curve for laparoscopic hemihepatectomy could potentially benefit the further implementation of the technique. Objective: To evaluate the extent and safety of the learning curve for laparoscopic hemihepatectomy. Design, Setting, and Participants: A prospectively collected single-center database containing all laparoscopic liver resections performed in our unit at the University Hospital Southampton National Health Service Foundation Trust between August 2003 and March 2015 was retrospectively reviewed; analyses were performed in December 2015. The study included 159 patients in whom a total laparoscopic right or left hemihepatectomy procedure was started (intention-to-treat analysis), including laparoscopic extended hemihepatectomies and hemihepatectomies with additional wedge resections, at a tertiary referral center specialized in laparoscopic hepato-pancreato-biliary surgery. Main Outcomes and Measures: Primary end points were clinically relevant complications (Clavien-Dindo grade >=III). The presence of a learning curve effect was assessed with a risk-adjusted cumulative sum analysis. Results: Of a total of 531 consecutive laparoscopic liver resections, 159 patients underwent total laparoscopic hemihepatectomy (105 right and 54 left). In a cohort with 67 men (42%), median age of 64 years (interquartile range [IQR], 51-73 years), and 110 resections (69%) for malignant lesions, the overall median operation time was 330 minutes (IQR, 270-391 minutes) and the median blood loss was 500 mL (IQR, 250-925 mL). Conversion to an open procedure occurred in 17 patients (11%). Clinically relevant complications occurred in 17 patients (11%), with 1% mortality (death within 90 days of surgery, n = 2). Comparison of outcomes over time showed a nonsignificant decrease in conversions (right: 14 [13%] and left: 3 [6%]), blood loss (right: 550 mL [IQR, 350-1150 mL] and left: 300 mL [IQR, 200-638 mL]), complications (right: 15 [14%] and left: 4 [7%]), and hospital stay (right: 5 days [IQR, 4-7 days] and left: 4 days [IQR, 3-5 days]). Risk-adjusted cumulative sum analysis demonstrated a learning curve of 55 laparoscopic hemihepatectomies for conversions. Conclusions and Relevance: Total laparoscopic hemihepatectomy is a feasible and safe procedure with an acceptable learning curve for conversions. Focus should now shift to providing adequate training opportunities for centers interested in implementing this technique. PMID- 27383569 TI - Investigation of absorptance and emissivity of thermal control coatings on Mg-Li alloys and OES analysis during PEO process. AB - Thermal control ceramic coatings on Mg-Li alloys have been successfully prepared in silicate electrolyte system by plasma electrolytic oxidation (PEO) method. The PEO coatings are mainly composed of crystallized Mg2SiO4 and MgO, which have typical porous structure with some bulges on the surface; OES analysis shows that the plasma temperature, which is influenced by the technique parameters, determines the formation of the coatings with different crystalline phases and morphologies, combined with "quick cooling effect" by the electrolyte; and the electron concentration is constant, which is related to the electric spark breakdown, determined by the nature of the coating and the interface of coating/electrolyte. Technique parameters influence the coating thickness, roughness and surface morphology, but do not change the coating composition in the specific PEO regime, and therefore the absorptance (alphaS) and emissivity (epsilon) of the coatings can be adjusted by the technique parameters through changing thickness and roughness in a certain degree. The coating prepared at 10 A/dm(2), 50 Hz, 30 min and 14 g/L Na2SiO3 has the minimum value of alphaS (0.35) and the maximum value of epsilon (0.82), with the balance temperature of 320 K. PMID- 27383570 TI - Cell reactions and immune responses to photodynamic therapy in oncology. AB - Photodynamic therapy (PDT) is a noninvasive, highly selective method for the treatment of diseases characterized by uncontrolled cell proliferation. It was clinically approved more than 30 years ago. PDT involves the selective uptake of a photosensitizer (PS) by neoplastic tissue, which is able to produce reactive oxygen species (ROS) upon irradiation with visible or near-infrared (NIR) light. ROS induce destruction of target cells and damage of tumor-associated vasculature and activate an antitumor immune response, leading to tumor regression. The execution of this process is attained by different mechanisms, including host immune responses and activation of cell death pathways: apoptosis and necrosis. PMID- 27383571 TI - Macrophages - silent enemies in juvenile idiopathic arthritis. AB - The inflammatory response by secretion of cytokines and other mediators is postulated as one of the most significant factors in the pathophysiology of juvenile idiopathic arthritis (JIA). The effect of macrophage action depends on the type of their activation. Classically activated macrophages (M1) are responsible for release of molecules crucial for joint inflammation. Alternatively activated macrophages (M2) may recognize self antigens by scavenger receptors and induce the immunological reaction leading to autoimmune diseases such as JIA. Molecules essential for JIA pathophysiology include: TNF-alpha, the production of which precedes synovial inflammation in rheumatoid arthritis; IL-1 as a key mediator of synovial damage; chemotactic factors for macrophages IL-8 and MCP-1; IL6, the level of which correlates with the radiological joint damage; MIF, promoting the secretion of TNF-alpha and IL-6; CCL20 and HIF, significant for the hypoxic synovial environment in JIA; GM-CSF, stimulating the production of macrophages; and IL-18, crucial for NK cell functions. Recognition of the role of macrophages creates the potential for a new therapeutic approach. PMID- 27383572 TI - Hen's egg as a source of valuable biologically active substances. AB - The aim of this article is to show current knowledge concerning valuable substances biologically active present in hen eggs and underline important nutritive role of hen eggs. Hen egg is a good source of nutrients such as proteins, vitamins (A, B2, B6, B12, D, E, K), minerals and lipids. The significant part of lipids is a group of unsaturated phospholipids, which are components of cell membranes, act protectively on the cardiovascular system and contribute to a decrease of cholesterol level and blood pressure. Therefore, the consumption of unsaturated phospholipids is recommended especially in patients suffering from diseases of the cardiovascular system. Another important substance is egg cystatin, which has a wide spectrum of biological functions, for example the ability to stimulate cell growth, inhibit inflammatory processes and has antibacterial and antiviral properties. Other substance presented in the egg white which helps fight bacteria is lysozyme. It is used in medicine as an aid in antibiotic therapy and analgesic in the course of infection, as well as in tumor malignancies. Among the components contained in the egg yolk there is also immunoglobulin Y which due to its therapeutic importance deserves special attention. Its use offers the possibility of replacing chemotherapeutic agents in the treatment of bacterial infections of digestive system, as well as an opportunity for the development of medicine associated with passive immunization of patients. The egg is a rich source of retinol which gradual depletion in the organism causes many eye pathologies. A very important and useful part of the egg, used in medicine is a shell and its membranes, due to the high collagen content relevant in the treatment of connective tissue diseases. PMID- 27383573 TI - Cannabinoids and haemostasis. AB - Elements of the endocannabinoid system (cannabinoid receptors CB1, CB2, CBPT and CBED, endocannabinoids, enzymes involved in the synthesis and metabolism of endocannabinoids) are located on the structures involved in the process of hemostasis. An increasing level of endocannabinoids was also observed in some pathological conditions, which may occur in disorders of hemostasis. At the same time, disconcertingly, there is an increased number of reports about incidents of cardiovascular events in smokers of marijuana. Experimental and clinical studies demonstrated multidirectional, often contradictory, effects of cannabinoids on hemostasis, including effects of the compounds on platelets, vascular endothelium, fibrinolysis and plasma coagulation systems. The mechanisms of action of cannabinoids on homeostasis depend on the cannabinoid receptors CB1, CB2, CBPT and CBED, receptors of other systems stimulated by endocannabinoids, as well as metabolites of endocannabinoids and nitrogen oxide. The range of biological functions of endo- and plant cannabinoids, expanded to include the process of hemostasis, may constitute a condition for their recognition as a new factor responsible for thromboembolism in smokers of marijuana, in pathological disorders with increased levels of endocannabinoids and in individuals with polymorphisms of FAAH C385A and A385A. On the other hand, there are compelling reasons for anti-hemostatic action of cannabinoids. PMID- 27383574 TI - Protease-activated receptors - biology and role in cancer. AB - The fact that blood coagulation disorders may accompany malignant disease is well established. However, many studies have shown that components of the haemostatic system may also elicit signaling leading to cancer developement and progression. The potential mechanism by which coagulation factors play a role in cancer invasion is not completely understood, but one hypothesis is that protease activated receptors (PARs) play a prominent role. PARs are transmembrane G protein-coupled receptors (GPCRs) that are activated by a unique proteolytic mechanism. They have important functions in haemostasis and inflammation but may also be implicated in cancer cell progression. Thrombin, tissue factor (TF) and matrix metalloproteinases (MMPs) are the main activators of these receptors. The mechanism of persistent activation of PARs was also described in cancer cells. Here, we discuss the physiological and pathological role of PARs with a particular focus on PARs' contribution to cancer biology. We also present therapeutic options tailored specifically to inhibition of PAR-induced signalling in cancer patients. PMID- 27383575 TI - Alzheimer's disease against peptides products of enzymatic cleavage of APP protein. Forming and variety of fibrillating peptides - some aspects. AB - Various and different peptides products resulting from enzymatic protein cleavage of Amyloid Precursor Proteins (APP) are the main agents in the pathophysiology of Alzheimer's disease (AD). Although relatively well-known, they still arouse interest leading to further intense and wide-ranging research. Their biology and physico-chemical properties still are challenging for basic, experimental research and are matter of scientific debate. The APP itself and its functions are still somewhat enigmatic and therefore it is also called the All Purpose Protein. Apart from well known amyloidogenic and antiamyloidogenic (non amyloidogenic) enzymatic cleavage pathways of APP protein this paper deals with issues connected with other, alternative pathways that seem to be interesting and important as well. They lead to other than Abeta forms of peptide products such as: N-APP, N-terminally cleavage products of APP (N-terminally truncated ) Abeta', gamma- secretase-independent pathway products that involve concerted cleavages of APP by alpha- and beta-secretase or products that emerge after caspase activity. Presence of all these peptides in CSF, ISF, blood serum and urine of the AD patients is crucial for successful diagnosis, giving rise to hope of their better detection and potentially better treatment of AD. Therefore, newly discovered products of the AbetaT domain cleavage (Abeta total i.e. full fibrillating domain of APP), Abeta type products and other peptides because of their biology and physico-chemical properties are very intriguing and deserve further experimental research. On the other hand after better recognition and better understanding their biology they might be enormously useful in the future for diagnosis and therapy for example Alzheimer's disease. PMID- 27383576 TI - Hepatoblastoma Biology Using Isotope Ratio Mass Spectrometry: Utility of a Unique Technique for the Analysis of Oncological Specimens. AB - INTRODUCTION: Hepatoblastoma is the most common primary liver tumor in children. However, it occurs rarely, with an incidence of 0.5-1.5 cases per million children. There is no clear explanation of the relationship between clinicopathologic features, therapy, and outcome in hepatoblastoma cases, so far. One of the most widely accepted prognostic factors in hepatoblastoma is histology of the tumor. The aim of the study was to determine the potential differences in biology of hepatoblastoma histological subtypes at the atomic level using the unique method of isotope ratio mass spectrometry, which is especially valuable in examination of small groups of biological samples. MATERIAL/METHODS: Twenty-four measurements of nitrogen stable isotope ratio, carbon stable isotope ratio and total carbon to nitrogen mass ratio in fetal and embryonal hepatoblastoma tissue were performed using a Sercon 20-22 Continuous Flow Isotope Ratio Mass Spectrometer (CF-IRMS) coupled with a Sercon SL elemental analyzer for simultaneous carbon-nitrogen-sulfur (NCS) analysis. RESULTS: A difference of about 1.7810/00 in stable nitrogen isotope 15N/14N ratio was found between examined hepatoblastoma histological subtypes. CONCLUSIONS: The prognosis in liver tumors cases in children may be challenging particularly because of the lack of versatile methods of its evaluation. Isotope ratio mass spectrometry allows one to determine the difference between hepatoblastoma histological subtypes and clearly indicates the cases with the best outcome. PMID- 27383577 TI - Mobile antibiotic resistance - the spread of genes determining the resistance of bacteria through food products. AB - In recent years, more and more antibiotics have become ineffective in the treatment of bacterial nfections. The acquisition of antibiotic resistance by bacteria is associated with circulation of genes in the environment. Determinants of antibiotic resistance may be transferred to pathogenic bacteria. It has been shown that conjugation is one of the key mechanisms responsible for spread of antibiotic resistance genes, which is highly efficient and allows the barrier to restrictions and modifications to be avoided. Some conjugative modules enable the transfer of plasmids even between phylogenetically distant bacterial species. Many scientific reports indicate that food is one of the main reservoirs of these genes. Antibiotic resistance genes have been identified in meat products, milk, fruits and vegetables. The reason for such a wide spread of antibiotic resistance genes is the overuse of antibiotics by breeders of plants and animals, as well as by horizontal gene transfer. It was shown, that resistance determinants located on mobile genetic elements, which are isolated from food products, can easily be transferred to another niche. The antibiotic resistance genes have been in the environment for 30 000 years. Their removal from food products is not possible, but the risks associated with the emergence of multiresistant pathogenic strains are very large. The only option is to control the emergence, selection and spread of these genes. Therefore measures are sought to prevent horizontal transfer of genes. Promising concepts involve the combination of developmental biology, evolution and ecology in the fight against the spread of antibiotic resistance. PMID- 27383578 TI - HSFA2 orchestrates transcriptional dynamics after heat stress in Arabidopsis thaliana. AB - In nature, stress is typically chronic or recurring and stress exposure can prime modified responses to recurring stress. Such stress priming may occur at the level of transcription. Here, we discuss the connection between plant stress memory, transcription, and chromatin modifications using the example of recurring heat stress. PMID- 27383580 TI - Iodine-mediated synthesis of heterocycles via electrophilic cyclization of alkynes. AB - Iodine has been recognized as an efficient, non-toxic, readily available and easy to-handle electrophilic reagent to favour halocyclization reactions for the synthesis of novel iodofunctionalized heterocyclic molecules that serve as versatile intermediates in synthetic organic chemistry. This review presents numerous useful methodologies for the synthesis of O, N, S, and Se-heterocycles through electrophilic cyclization via the attack of an electrophile on the C(sp) bond of alkynes. The cyclization proceeds under mild reaction conditions and tolerates a wide variety of functional groups. PMID- 27383579 TI - Incidence and risk factors of fever in a contemporary cohort of HIV-patients with good access to antiretroviral therapy. AB - OBJECTIVE: To study incidence and to determine risk factors of fever in a contemporary cohort of HIV-infected patients with access to antiretroviral therapy. METHODS: Prospective study in a cohort of HIV-infected patients in Belgium from 2009 to 2013. RESULTS: 759 patients were followed for a total of 2136 patient years. The incidence of fever was low, with an incidence rate of 0.103 (95% CI 0.078; 0.135) febrile episodes per patient per year for temperature 38.3 degrees C or higher measured by a health care provider. Gender, age, ethnicity, and calendar year of measurement were no significant risk factors for fever in univariable analysis, but recent HIV diagnosis, prior AIDS, nadir CD4 cell count, last CD4 cell count, and viral load were, as were use of antiretroviral therapy, recent start of antiretroviral therapy and recent switch of antiretroviral therapy. Recent stop of antiretroviral therapy was no significant risk factor. In multivariable analysis prior AIDS, last CD4 and viral load remained significant risk factors, but use of antiretroviral therapy not. CONCLUSION: In this contemporary cohort, incidence of fever was low but CD4 cell count less than 200/mm3 remained associated with the highest incidence of fever. PMID- 27383581 TI - Relative impact of a patient blood management program on utilization of all three major blood components. AB - BACKGROUND: Although patient blood management (PBM) programs clearly reduce transfusion overuse, the relative impact on red blood cell (RBC), plasma, and platelet (PLT) utilization is unclear. STUDY DESIGN AND METHODS: A retrospective analysis of electronic records was conducted at a medium-sized academic hospital to assess blood utilization for all inpatients admitted during 1-year periods before (n = 20,531) and after (n = 19,477) PBM efforts began in September 2014. Transfusion guideline compliance and overall utilization were assessed for RBCs, plasma, and PLTs. The primary PBM efforts included education on evidence-based transfusion guidelines, decision support in the computerized provider order entry system, and distribution of provider-specific reports showing comparison to peers for guideline compliance. Cost avoidance was determined by two methods (acquisition cost and activity-based cost), and clinical outcomes were compared during the two periods. RESULTS: For RBCs, orders outside hospital guidelines decreased (from 23.9% to 17.1%, p < 0.001), and utilization decreased by 12% (p < 0.035). For plasma and PLTs, both orders outside guidelines and utilization changed minimally. Overall cost avoidance was $181,887/year by acquisition cost (and from $582,039 to $873,058/year by activity-based cost), 93% of which was attributed to reduction in RBC utilization. Length of stay, morbidity, and mortality were unchanged. CONCLUSIONS: Our findings demonstrate a greater opportunity for reducing RBC compared to plasma and PLT utilization. A properly implemented PBM program has potential to reduce unnecessary transfusions and their associated risk and costs, without compromising clinical outcomes. PMID- 27383582 TI - Poly(ethylene glycol)-co-methacrylamide-co-acrylic acid based nanogels for delivery of doxorubicin. AB - Polymeric nanogels have been widely explored for their potential application as delivery carriers for cancer therapeutics. The ability of nanogels to encapsulate therapeutics by simple diffusion mechanism and the ease of their fabrication to impart target specificity in addition to their ability to get internalized into target cells make them good candidates for drug delivery. The present study aims to investigate the applicability of poly(ethylene glycol)-co-methacrylamide-co acrylic acid (PMA)-based nanogels as a viable option for the delivery of doxorubicin (DOX). The nanogels were synthesized by free radical polymerization in an inverse mini-emulsion and characterized by nuclear magnetic resonance spectroscopy ((1)H NMR), Fourier transform infrared spectroscopy, dynamic light scattering, transmission electron microscopy (TEM), X-ray diffraction and differential scanning calorimetry. DOX was physically incorporated into the nanogels (PMA-DOX) and the mechanism of its in vitro release was studied. TEM experiment revealed spherical morphology of nanogels and the hydrodynamic diameter of the neat nanogels was in the range of 160 +/- 46.95 nm. The size of the nanogels increased from 235.1 +/- 28.46 to 403.7 +/- 89.89 nm with the increase in drug loading capacity from 4.68 +/- 0.03 to 13.71 +/- 0.01%. The sustained release of DOX was observed upto 80 h and the release rate decreased with increased loading capacity following anomalous release mechanism as indicated by the value of diffusion exponent (n = 0.64-0.75) obtained from Korsmeyer-Peppas equation. Further, cytotoxicity evaluation of PMA-DOX nanogels on HeLa cells resulted in relatively higher efficacy (IC50~5.88 MUg/mL) as compared to free DOX (IC50~7.24 MUg/mL) thus demonstrating that the preparation is potentially a promising drug delivery carrier. PMID- 27383583 TI - Unprecedented Electro-Optic Performance in Lead-Free Transparent Ceramics. AB - A high-performance lead-free electro-optic (EO) transparent material is introduced and used in an EO device operating up to 10 kHz. The BZT-BCT ceramic, named as BXT, has an effective DC EO coefficient, rc = 530 pm V-1 , which is higher than state-of-the-art materials such as LiNbO3 . The high EO response can be leveraged for miniaturization and/or reduction of the operating voltage of EO devices. PMID- 27383584 TI - SfN Journals: Two Paths, One Goal: Sharing Strong Science. PMID- 27383585 TI - Are Movement Preparation and Movement Initiation Truly Independent? PMID- 27383586 TI - Selective Deletion of Astroglial FMRP Dysregulates Glutamate Transporter GLT1 and Contributes to Fragile X Syndrome Phenotypes In Vivo. AB - How the loss of fragile X mental retardation protein (FMRP) in different brain cell types, especially in non-neuron glial cells, induces fragile X syndrome (FXS) phenotypes has just begun to be understood. In the current study, we generated inducible astrocyte-specific Fmr1 conditional knock-out mice (i-astro Fmr1-cKO) and restoration mice (i-astro-Fmr1-cON) to study the in vivo modulation of FXS synaptic phenotypes by astroglial FMRP. We found that functional expression of glutamate transporter GLT1 is 40% decreased in i-astro-Fmr1-cKO somatosensory cortical astrocytes in vivo, which can be fully rescued by the selective re-expression of FMRP in astrocytes in i-astro-Fmr1-cON mice. Although the selective loss of astroglial FMRP only modestly increases spine density and length in cortical pyramidal neurons, selective re-expression of FMRP in astrocytes significantly attenuates abnormal spine morphology in these neurons of i-astro-Fmr1-cON mice. Moreover, we found that basal protein synthesis levels and immunoreactivity of phosphorylated S6 ribosomal protein (p-s6P) is significantly increased in i-astro-Fmr1-cKO mice, while the enhanced cortical protein synthesis observed in Fmr1 KO mice is mitigated in i-astro-Fmr1-cON mice. Furthermore, ceftriaxone-mediated upregulation of surface GLT1 expression restores functional glutamate uptake and attenuates enhanced neuronal excitability in Fmr1 KO mice. In particular, ceftriaxone significantly decreases the growth rate of abnormally accelerated body weight and completely corrects spine abnormality in Fmr1 KO mice. Together, these results show that the selective loss of astroglial FMRP contributes to cortical synaptic deficits in FXS, presumably through dysregulated astroglial glutamate transporter GLT1 and impaired glutamate uptake. These results suggest the involvement of astrocyte-mediated mechanisms in the pathogenesis of FXS. SIGNIFICANCE STATEMENT: Previous studies to understand how the loss of function of fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS) have largely focused on neurons; whether the selective loss of astroglial FMRP in vivo alters astrocyte functions and contributes to the pathogenesis of FXS remain essentially unknown. This has become a long-standing unanswered question in the fragile X field, which is also relevant to autism pathogenesis. Our current study generated astrocyte-specific Fmr1 conditional knock-out and restoration mice, and provided compelling evidence that the selective loss of astroglial FMRP contributes to cortical synaptic deficits in FXS, likely through the dysregulated astroglial glutamate transporter GLT1 expression and impaired glutamate uptake. These results demonstrate previously undescribed astrocyte-mediated mechanisms in the pathogenesis of FXS. PMID- 27383587 TI - Chronic Cognitive Dysfunction after Traumatic Brain Injury Is Improved with a Phosphodiesterase 4B Inhibitor. AB - Learning and memory impairments are common in traumatic brain injury (TBI) survivors. However, there are no effective treatments to improve TBI-induced learning and memory impairments. TBI results in decreased cAMP signaling and reduced cAMP-response-element binding protein (CREB) activation, a critical pathway involved in learning and memory. TBI also acutely upregulates phosphodiesterase 4B2 (PDE4B2), which terminates cAMP signaling by hydrolyzing cAMP. We hypothesized that a subtype-selective PDE4B inhibitor could reverse the learning deficits induced by TBI. To test this hypothesis, adult male Sprague Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury. At 3 months postsurgery, animals were administered a selective PDE4B inhibitor or vehicle before cue and contextual fear conditioning, water maze training and a spatial working memory task. Treatment with the PDE4B inhibitor significantly reversed the TBI-induced deficits in cue and contextual fear conditioning and water maze retention. To further understand the underlying mechanisms of these memory impairments, we examined hippocampal long-term potentiation (LTP). TBI resulted in a significant reduction in basal synaptic transmission and impaired expression of LTP. Treatment with the PDE4B inhibitor significantly reduced the deficits in basal synaptic transmission and rescued LTP expression. The PDE4B inhibitor reduced tumor necrosis factor-alpha levels and increased phosphorylated CREB levels after TBI, suggesting that this drug inhibited molecular pathways in the brain known to be regulated by PDE4B. These results suggest that a subtype-selective PDE4B inhibitor is a potential therapeutic to reverse chronic learning and memory dysfunction and deficits in hippocampal synaptic plasticity following TBI. SIGNIFICANCE STATEMENT: Currently, there are an estimated 3.2-5.3 million individuals living with disabilities from traumatic brain injury (TBI) in the United States, and 8 of 10 of these individuals report cognitive disabilities (Thurman et al., 1999; Lew et al., 2006; Zaloshnja et al., 2008). One of the molecular mechanisms associated with chronic cognitive disabilities is impaired cAMP signaling in the hippocampus. In this study, we report that a selective phosphodiesterase 4B (PDE4B) inhibitor reduces chronic cognitive deficits after TBI and rescues deficits in hippocampal long-term potentiation. These results suggest that PDE4B inhibition has the potential to improve learning and memory ability and overall functioning for people living with TBI. PMID- 27383588 TI - Transient Oxygen/Glucose Deprivation Causes a Delayed Loss of Mitochondria and Increases Spontaneous Calcium Signaling in Astrocytic Processes. AB - Recently, mitochondria have been localized to astrocytic processes where they shape Ca(2+) signaling; this relationship has not been examined in models of ischemia/reperfusion. We biolistically transfected astrocytes in rat hippocampal slice cultures to facilitate fluorescent confocal microscopy, and subjected these slices to transient oxygen/glucose deprivation (OGD) that causes delayed excitotoxic death of CA1 pyramidal neurons. This insult caused a delayed loss of mitochondria from astrocytic processes and increased colocalization of mitochondria with the autophagosome marker LC3B. The losses of neurons in area CA1 and mitochondria in astrocytic processes were blocked by ionotropic glutamate receptor (iGluR) antagonists, tetrodotoxin, ziconotide (Ca(2+) channel blocker), two inhibitors of reversed Na(+)/Ca(2+) exchange (KB-R7943, YM-244769), or two inhibitors of calcineurin (cyclosporin-A, FK506). The effects of OGD were mimicked by NMDA. The glutamate uptake inhibitor (3S)-3-[[3-[[4 (trifluoromethyl)benzoyl]amino]phenyl]methoxy]-l-aspartate increased neuronal loss after OGD or NMDA, and blocked the loss of astrocytic mitochondria. Exogenous glutamate in the presence of iGluR antagonists caused a loss of mitochondria without a decrease in neurons in area CA1. Using the genetic Ca(2+) indicator Lck-GCaMP-6S, we observed two types of Ca(2+) signals: (1) in the cytoplasm surrounding mitochondria (mitochondrially centered) and (2) traversing the space between mitochondria (extramitochondrial). The spatial spread, kinetics, and frequency of these events were different. The amplitude of both types was doubled and the spread of both types changed by ~2-fold 24 h after OGD. Together, these data suggest that pathologic activation of glutamate transport and increased astrocytic Ca(2+) through reversed Na(+)/Ca(2+) exchange triggers mitochondrial loss and dramatic increases in Ca(2+) signaling in astrocytic processes. SIGNIFICANCE STATEMENT: Astrocytes, the most abundant cell type in the brain, are vital integrators of signaling and metabolism. Each astrocyte consists of many long, thin branches, called processes, which ensheathe vasculature and thousands of synapses. Mitochondria occupy the majority of each process. This occupancy is decreased by ~50% 24 h after an in vitro model of ischemia/reperfusion injury, due to delayed fragmentation and mitophagy. The mechanism appears to be independent of neuropathology, instead involving an extended period of high glutamate uptake into astrocytes. Our data suggest that mitochondria serve as spatial buffers, and possibly even as a source of calcium signals in astrocytic processes. Loss of mitochondria resulted in drastically altered calcium signaling that could disrupt neurovascular coupling and gliotransmission. PMID- 27383591 TI - When Synchronizing to Rhythms Is Not a Good Thing: Modulations of Preparatory and Post-Target Neural Activity When Shifting Attention Away from On-Beat Times of a Distracting Rhythm. AB - Environmental rhythms potently drive predictive resource allocation in time, typically leading to perceptual and motor benefits for on-beat, relative to off beat, times, even if the rhythmic stream is not intentionally used. In two human EEG experiments, we investigated the behavioral and electrophysiological expressions of using rhythms to direct resources away from on-beat times. This allowed us to distinguish goal-directed attention from the automatic capture of attention by rhythms. The following three conditions were compared: (1) a rhythmic stream with targets appearing frequently at a fixed off-beat position; (2) a rhythmic stream with targets appearing frequently at on-beat times; and (3) a nonrhythmic stream with matched target intervals. Shifting resources away from on-beat times was expressed in the slowing of responses to on-beat targets, but not in the facilitation of off-beat targets. The shifting of resources was accompanied by anticipatory adjustment of the contingent negative variation (CNV) buildup toward the expected off-beat time. In the second experiment, off-beat times were jittered, resulting in a similar CNV adjustment and also in preparatory amplitude reduction of beta-band activity. Thus, the CNV and beta activity track the relevance of time points and not the rhythm, given sufficient incentive. Furthermore, the effects of task relevance (appearing in a task relevant vs irrelevant time) and rhythm (appearing on beat vs off beat) had additive behavioral effects and also dissociable neural manifestations in target evoked activity: rhythm affected the target response as early as the P1 component, while relevance affected only the later N2 and P3. Thus, these two factors operate by distinct mechanisms. SIGNIFICANCE STATEMENT: Rhythmic streams are widespread in our environment, and are typically conceptualized as automatic, bottom-up resource attractors to on-beat times-preparatory neural activity peaks at rhythm-on-beat times and behavioral benefits are seen to on-beat compared with off-beat targets. We show that this behavioral benefit is reversed when targets are more frequent at off-beat compared with on-beat times, and that preparatory neural activity, previously thought to be driven by the rhythm to on-beat times, is adjusted toward off-beat times. Furthermore, the effect of this relevance based shifting on target-evoked brain activity was dissociable from the automatic effect of rhythms. Thus, rhythms can act as cues for flexible resource allocation according to the goal relevance of each time point, instead of being obligatory resource attractors. PMID- 27383590 TI - Deletion of Suppressor of Cytokine Signaling 3 from Forebrain Neurons Delays Infertility and Onset of Hypothalamic Leptin Resistance in Response to a High Caloric Diet. AB - The cellular processes that cause high caloric diet (HCD)-induced infertility are poorly understood but may involve upregulation of suppressor of cytokine signaling (SOCS-3) proteins that are associated with hypothalamic leptin resistance. Deletion of SOCS-3 from brain cells is known to protect mice from diet-induced obesity, but the effects on HCD-induced infertility are unknown. We used neuron-specific SOCS3 knock-out mice to elucidate this and the effects on regional hypothalamic leptin resistance. As expected, male and female neuron specific SOCS3 knock-out mice were protected from HCD-induced obesity. While female wild-type mice became infertile after 4 months of HCD feeding, infertility onset in knock-out females was delayed by 4 weeks. Similarly, knock-out mice had delayed leptin resistance development in the medial preoptic area and anteroventral periventricular nucleus, regions important for generation of the surge of GnRH and LH that induces ovulation. We therefore tested whether the suppressive effects of HCD on the estradiol-induced GnRH/LH surge were overcome by neuron-specific SOCS3 knock-out. Although only 20% of control HCD-mice experienced a preovulatory-like LH surge, LH surges could be induced in almost all neuron-specific SOCS3 knock-out mice on this diet. In contrast to females, HCD-fed male mice did not exhibit any fertility decline compared with low caloric diet-fed males despite their resistance to the satiety effects of leptin. These data show that deletion of SOCS3 delays the onset of leptin resistance and infertility in HCD-fed female mice, but given continued HCD feeding this state does eventually occur, presumably in response to other mechanisms inhibiting leptin signal transduction. SIGNIFICANCE STATEMENT: Obesity is commonly associated with infertility in humans and other animals. Treatments for human infertility show a decreased success rate with increasing body mass index. A hallmark of obesity is an increase in circulating leptin levels; despite this, the brain responds as if there were low levels of leptin, leading to increased appetite and suppressed fertility. Here we show that leptin resistant infertility is caused in part by the leptin signaling molecule SOCS3. Deletion of SOCS3 from brain neurons delays the onset of diet-induced infertility. PMID- 27383589 TI - Altered Development of Synapse Structure and Function in Striatum Caused by Parkinson's Disease-Linked LRRK2-G2019S Mutation. AB - Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) can cause Parkinson's disease (PD), and the most common disease-associated mutation, G2019S, increases kinase activity. Because LRRK2 expression levels rise during synaptogenesis and are highest in dorsal striatal spiny projection neurons (SPNs), we tested the hypothesis that the LRRK2-G2019S mutation would alter development of excitatory synaptic networks in dorsal striatum. To circumvent experimental confounds associated with LRRK2 overexpression, we used mice expressing LRRK2-G2019S or D2017A (kinase-dead) knockin mutations. In whole-cell recordings, G2019S SPNs exhibited a fourfold increase in sEPSC frequency compared with wild-type SPNs in postnatal day 21 mice. Such heightened neural activity was increased similarly in direct- and indirect-pathway SPNs, and action potential dependent activity was particularly elevated. Excitatory synaptic activity in D2017A SPNs was similar to wild type, indicating a selective effect of G2019S. Acute exposure to LRRK2 kinase inhibitors normalized activity, supporting that excessive neural activity in G2019S SPNs is mediated directly and is kinase dependent. Although dendritic arborization and densities of excitatory presynaptic terminals and postsynaptic dendritic spines in G2019S SPNs were similar to wild type, G2019S SPNs displayed larger spines that were matched functionally by a shift toward larger postsynaptic response amplitudes. Acutely isolating striatum from overlying neocortex normalized sEPSC frequency in G2019S mutants, supporting that abnormal corticostriatal activity is involved. These findings indicate that the G2019S mutation imparts a gain-of-abnormal function to SPN activity and morphology during a stage of development when activity can permanently modify circuit structure and function. SIGNIFICANCE STATEMENT: Mutations in the kinase domain of leucine-rich repeat kinase 2 (LRRK2) follow Parkinson's disease (PD) heritability. How such mutations affect brain function is poorly understood. LRRK2 expression levels rise after birth at a time when synapses are forming and are highest in dorsal striatum, suggesting that LRRK2 regulates development of striatal circuits. During a period of postnatal development when activity plays a large role in permanently shaping neural circuits, our data show how the most common PD-causing LRRK2 mutation dramatically alters excitatory synaptic activity and the shape of postsynaptic structures in striatum. These findings provide new insight into early functional and structural aberrations in striatal connectivity that may predispose striatal circuitry to both motor and nonmotor dysfunction later in life. PMID- 27383592 TI - Temporal Dynamics of Sensorimotor Networks in Effort-Based Cost-Benefit Valuation: Early Emergence and Late Net Value Integration. AB - Although physical effort can impose significant costs on decision-making, when and how effort cost information is incorporated into choice remains contested, reflecting a larger debate over the role of sensorimotor networks in specifying behavior. Serial information processing models, in which motor circuits simply implement the output of cognitive systems, hypothesize that effort cost factors into decisions relatively late, via integration with stimulus values into net (combined) value signals in dorsomedial frontal cortex (dmFC). In contrast, ethology-inspired approaches suggest a more active role for the dorsal sensorimotor stream, with effort cost signals emerging rapidly after stimulus onset. Here we investigated the time course of effort cost integration using event-related potentials in hungry human subjects while they made decisions about expending physical effort for appetitive foods. Consistent with the ethological perspective, we found that effort cost was represented from as early as 100-250 ms after stimulus onset, localized to dorsal sensorimotor regions including middle cingulate, somatosensory, and motor/premotor cortices. However, examining the same data time-locked to motor output revealed net value signals combining stimulus value and effort cost approximately -400 ms before response, originating from sensorimotor areas including dmFC, precuneus, and posterior parietal cortex. Granger causal connectivity analysis of the motor effector signal in the time leading to response showed interactions between these sensorimotor regions and ventrolateral prefrontal cortex, a structure associated with adjusting behavior response mappings. These results suggest that rapid activation of sensorimotor regions interacts with cognitive valuation systems, producing a net value signal reflecting both physical effort and reward contingencies. SIGNIFICANCE STATEMENT: Although physical effort imposes a cost on choice, when and how effort cost influences neural correlates of decision-making remains contested. This dispute reflects a larger disagreement between cognitive neuroscience and ethology over the role of sensorimotor systems in behavior: are sensorimotor circuits merely implementing the late-stage output of cognitive systems, or engaged rapidly and interactively from early in decision-making? We find that, although early representation of effort cost is associated with sensorimotor regions, these signals are also integrated with cognitive stimulus value representations in the time leading up to motor response. These data suggest that sensorimotor networks interact dynamically with cognitive systems to guide decision-making, providing a first step toward reconciling differing perspectives on sensorimotor roles in valuation and choice. PMID- 27383594 TI - Selective Attention to Visual Stimuli Using Auditory Distractors Is Altered in Alpha-9 Nicotinic Receptor Subunit Knock-Out Mice. AB - During selective attention, subjects voluntarily focus their cognitive resources on a specific stimulus while ignoring others. Top-down filtering of peripheral sensory responses by higher structures of the brain has been proposed as one of the mechanisms responsible for selective attention. A prerequisite to accomplish top-down modulation of the activity of peripheral structures is the presence of corticofugal pathways. The mammalian auditory efferent system is a unique neural network that originates in the auditory cortex and projects to the cochlear receptor through the olivocochlear bundle, and it has been proposed to function as a top-down filter of peripheral auditory responses during attention to cross modal stimuli. However, to date, there is no conclusive evidence of the involvement of olivocochlear neurons in selective attention paradigms. Here, we trained wild-type and alpha-9 nicotinic receptor subunit knock-out (KO) mice, which lack cholinergic transmission between medial olivocochlear neurons and outer hair cells, in a two-choice visual discrimination task and studied the behavioral consequences of adding different types of auditory distractors. In addition, we evaluated the effects of contralateral noise on auditory nerve responses as a measure of the individual strength of the olivocochlear reflex. We demonstrate that KO mice have a reduced olivocochlear reflex strength and perform poorly in a visual selective attention paradigm. These results confirm that an intact medial olivocochlear transmission aids in ignoring auditory distraction during selective attention to visual stimuli. SIGNIFICANCE STATEMENT: The auditory efferent system is a neural network that originates in the auditory cortex and projects to the cochlear receptor through the olivocochlear system. It has been proposed to function as a top-down filter of peripheral auditory responses during attention to cross-modal stimuli. However, to date, there is no conclusive evidence of the involvement of olivocochlear neurons in selective attention paradigms. Here, we studied the behavioral consequences of adding different types of auditory distractors in a visual selective attention task in wild-type and alpha-9 nicotinic receptor knock-out (KO) mice. We demonstrate that KO mice perform poorly in the selective attention paradigm and that an intact medial olivocochlear transmission aids in ignoring auditory distractors during attention. PMID- 27383593 TI - M1 ipRGCs Influence Visual Function through Retrograde Signaling in the Retina. AB - Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs, with five subtypes named M1-M5) are a unique subclass of RGCs with axons that project directly to many brain nuclei involved in non-image-forming functions such as circadian photoentrainment and the pupillary light reflex. Recent evidence suggests that melanopsin-based signals also influence image forming visual function, including light adaptation, but the mechanisms involved are unclear. Intriguingly, a small population of M1 ipRGCs have intraretinal axon collaterals that project toward the outer retina. Using genetic mouse models, we provide three lines of evidence showing that these axon collaterals make connections with upstream dopaminergic amacrine cells (DACs): (1) ipRGC signaling to DACs is blocked by tetrodotoxin both in vitro and in vivo, indicating that ipRGC-to-DAC transmission requires voltage-gated Na(+) channels; (2) this transmission is partly dependent on N-type Ca(2+) channels, which are possibly expressed in the axon collateral terminals of ipRGCs; and (3) fluorescence microscopy reveals that ipRGC axon collaterals make putative presynaptic contact with DACs. We further demonstrate that elimination of M1 ipRGCs attenuates light adaptation, as evidenced by an impaired electroretinogram b-wave from cones, whereas a dopamine receptor agonist can potentiate the cone-driven b-wave of retinas lacking M1 ipRGCs. Together, the results strongly suggest that ipRGCs transmit luminance signals retrogradely to the outer retina through the dopaminergic system and in turn influence retinal light adaptation. SIGNIFICANCE STATEMENT: Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) comprise a third class of retinal photoreceptors that are known to mediate physiological responses such as circadian photoentrainment. However, investigation into whether and how ipRGCs contribute to vision has just begun. Here, we provide convergent anatomical and physiological evidence that axon collaterals of ipRGCs constitute a centrifugal pathway to DACs, conveying melanopsin-based signals from the innermost retina to the outer retina. We further demonstrate that retrograde signals likely influence visual processing because elimination of axon collateral-bearing ipRGCs impairs light adaptation by limiting dopamine-dependent facilitation of the cone pathway. Our findings strongly support the hypothesis that retrograde melanopsin-based signaling influences visual function locally within the retina, a notion that refutes the dogma that RGCs only provide physiological signals to the brain. PMID- 27383595 TI - Aging-Resilient Associations between the Arcuate Fasciculus and Vocabulary Knowledge: Microstructure or Morphology? AB - Vocabulary knowledge is one of the few cognitive functions that is relatively preserved in older adults, but the reasons for this relative preservation have not been well delineated. We tested the hypothesis that individual differences in vocabulary knowledge are influenced by arcuate fasciculus macrostructure (i.e., shape and volume) properties that remain stable during the aging process, rather than white matter microstructure that demonstrates age-related declines. Vocabulary was not associated with age compared to pronounced age-related declines in cognitive processing speed across 106 healthy adults (19.92-88.29 years) who participated in this neuroimaging experiment. Fractional anisotropy in the left arcuate fasciculus was significantly related to individual variability in vocabulary. This effect was present despite marked age-related differences in a T1-weighted/T2-weighted ratio (T1w/T2w) estimate of myelin that were observed throughout the left arcuate fasciculus and associated with age-related differences in cognitive processing speed. However, atypical patterns of arcuate fasciculus morphology or macrostructure were associated with decreased vocabulary knowledge. These results suggest that deterioration of tissue in the arcuate fasciculus occurs with normal aging, while having limited impact on tract organization that underlies individual differences in the acquisition and retrieval of lexical and semantic information. SIGNIFICANCE STATEMENT: Vocabulary knowledge is resilient to widespread age-related declines in brain structure that limit other cognitive functions. We tested the hypothesis that arcuate fasciculus morphology, which supports the development of reading skills that bolster vocabulary, could explain this relative preservation. We disentangled (1) the effects of age-related declines in arcuate microstructure (mean diffusivity; myelin content estimate) that predicted cognitive processing speed but not vocabulary, from (2) relatively stable arcuate macrostructure (shape/volume) that explained significant variance in an age-independent association between fractional anisotropy and vocabulary. This latter result may reflect differences in fiber trajectory and organization that are resilient to aging. We propose that developmental sculpting of the arcuate fasciculus determines acquisition, storage, and access of lexical information across the adult lifespan. PMID- 27383596 TI - Functional Interactions between Mammalian Respiratory Rhythmogenic and Premotor Circuitry. AB - Breathing in mammals depends on rhythms that originate from the preBotzinger complex (preBotC) of the ventral medulla and a network of brainstem and spinal premotor neurons. The rhythm-generating core of the preBotC, as well as some premotor circuits, consist of interneurons derived from Dbx1-expressing precursors (Dbx1 neurons), but the structure and function of these networks remain incompletely understood. We previously developed a cell-specific detection and laser ablation system to interrogate respiratory network structure and function in a slice model of breathing that retains the preBotC, the respiratory related hypoglossal (XII) motor nucleus and XII premotor circuits. In spontaneously rhythmic slices, cumulative ablation of Dbx1 preBotC neurons decreased XII motor output by ~50% after ~15 cell deletions, and then decelerated and terminated rhythmic function altogether as the tally increased to ~85 neurons. In contrast, cumulatively deleting Dbx1 XII premotor neurons decreased motor output monotonically but did not affect frequency nor stop XII output regardless of the ablation tally. Here, we couple an existing preBotC model with a premotor population in several topological configurations to investigate which one may replicate the laser ablation experiments best. If the XII premotor population is a "small-world" network (rich in local connections with sparse long range connections among constituent premotor neurons) and connected with the preBotC such that the total number of incoming synapses remains fixed, then the in silico system successfully replicates the in vitro laser ablation experiments. This study proposes a feasible configuration for circuits consisting of Dbx1 derived interneurons that generate inspiratory rhythm and motor pattern. SIGNIFICANCE STATEMENT: To produce a breathing-related motor pattern, a brainstem core oscillator circuit projects to a population of premotor interneurons, but the assemblage of this network remains incompletely understood. Here we applied network modeling and numerical simulation to discover respiratory circuit configurations that successfully replicate photonic cell ablation experiments targeting either the core oscillator or premotor network, respectively. If premotor neurons are interconnected in a so-called "small-world" network with a fixed number of incoming synapses balanced between premotor and rhythmogenic neurons, then our simulations match their experimental benchmarks. These results provide a framework of experimentally testable predictions regarding the rudimentary structure and function of respiratory rhythm- and pattern-generating circuits in the brainstem of mammals. PMID- 27383597 TI - Differential Somatic Ca2+ Channel Profile in Midbrain Dopaminergic Neurons. AB - Dopaminergic (DA) neurons located in the ventral midbrain continuously generate a slow endogenous pacemaker activity, the mechanism of which is still debated. It has been suggested that, in the substantia nigra pars compacta (SNc), the pacemaking relies more on Ca(2+) channels and that the density of L-type Ca(2+) channels is higher in these DA neurons than in those located in the ventral tegmental area (VTA). This might lead to a higher Ca(2+) load in SNc DA neurons and explain their higher susceptibility to degeneration. However, direct evidence for this hypothesis is lacking. We found that the L-type current and channel density are indeed higher in the somata of rat SNc DA neurons and that this current undergoes less inactivation in this region. Nonstationary fluctuation analysis measurements showed a much higher number of L-type channels in the soma of SNc DA neurons, as well as a smaller single-channel conductance, pointing to a possible different molecular identity of L-type channels in DA neurons from the two areas. A major consequence of this is that pacemaking and, even more so, bursting are associated with a larger Ca(2+) entry through L-type channels in SNc DA neurons than in their VTA counterparts. Our results establish a molecular and functional difference between two populations of midbrain DA neurons that may contribute to their differential sensitivity to neurodegeneration. SIGNIFICANCE STATEMENT: Dopamine neurons from the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) are involved in various brain functions, such as movement initiation and goal directed behavior, respectively. This work shows that, although both neurons fire in a similar regular and slow pacemaker mode, this firing activity is supported by different calcium channel landscapes. Indeed, the L-type calcium current is larger in the soma of dopamine neurons of the SNc, leading to a higher charge transfer through L-type channels during pacemaking and bursting. Therefore, these neurons may be physiologically exposed to a larger stress than their neighbors from the VTA. PMID- 27383598 TI - Lack of Intrinsic GABAergic Connections in the Thalamic Reticular Nucleus of the Mouse. AB - It is generally thought that neurons in the thalamic reticular nucleus (TRN) form GABAergic synapses with other TRN neurons and that these interconnections are important for the function of the TRN. However, the existence of such intrinsic connections is controversial. We combine two complementary approaches to examine intrinsic GABAergic connections in the TRN of the mouse. We find that optogenetic stimulation of TRN neurons and their axons evokes GABAergic IPSCs in TRN neurons in mice younger than 2 weeks of age but fails to do so after that age. Blocking synaptic release from TRN neurons through conditional deletion of vesicular GABA transporter has no effect on spontaneous IPSCs recorded in TRN neurons aged 2 weeks or older while dramatically reducing GABAergic transmission in thalamic relay neurons. These results demonstrate that except for a short period after birth, the TRN of the mouse lacks intrinsic GABAergic connections. SIGNIFICANCE STATEMENT: The thalamic reticular nucleus has a critical role in modulating information transfer from the thalamus to the cortex. It has been proposed that neurons in the thalamic reticular nucleus are interconnected through GABAergic synapses and that these connections serve important functions. Our results show that except for the first 2 weeks after birth, the thalamic reticular nucleus of the mouse lacks intrinsic GABAergic connections. PMID- 27383599 TI - Hippocampal MicroRNA-124 Enhances Chronic Stress Resilience in Mice. AB - Chronic stress-induced aberrant gene expression in the brain and subsequent dysfunctional neuronal plasticity have been implicated in the etiology and pathophysiology of mood disorders. In this study, we examined whether altered expression of small, regulatory, noncoding microRNAs (miRNAs) contributes to the depression-like behaviors and aberrant neuronal plasticity associated with chronic stress. Mice exposed to chronic ultra-mild stress (CUMS) exhibited increased depression-like behaviors and reduced hippocampal expression of the brain-enriched miRNA-124 (miR-124). Aberrant behaviors and dysregulated miR-124 expression were blocked by chronic treatment with an antidepressant drug. The depression-like behaviors are likely not conferred directly by miR-124 downregulation because neither viral-mediated hippocampal overexpression nor intrahippocampal infusion of an miR-124 inhibitor affected depression-like behaviors in nonstressed mice. However, viral-mediated miR-124 overexpression in hippocampal neurons conferred behavioral resilience to CUMS, whereas inhibition of miR-124 led to greater behavioral susceptibility to a milder stress paradigm. Moreover, we identified histone deacetylase 4 (HDAC4), HDAC5, and glycogen synthase kinase 3beta (GSK3beta) as targets for miR-124 and found that intrahippocampal infusion of a selective HDAC4/5 inhibitor or GSK3 inhibitor had antidepressant-like actions on behavior. We propose that miR-124-mediated posttranscriptional controls of HDAC4/5 and GSK3beta expressions in the hippocampus have pivotal roles in susceptibility/resilience to chronic stress. SIGNIFICANCE STATEMENT: Depressive disorders are a major public health concern worldwide. Although a clear understanding of the etiology of depression is still lacking, chronic stress-elicited aberrant neuronal plasticity has been implicated in the pathophysiology of depression. We show that the hippocampal expression of microRNA-124 (miR-124), an endogenous small, noncoding RNA that represses gene expression posttranscriptionally, controls resilience/susceptibility to chronic stress-induced depression-like behaviors. These effects on depression-like behaviors may be mediated through regulation of the mRNA or protein expression levels of histone deacetylases HDAC4/5 and glycogen synthase kinase 3beta, all highly conserved miR-124 targets. Moreover, miR-124 contributes to stress-induced dendritic hypotrophy and reduced spine density of dentate gyrus granule neurons. Modulation of hippocampal miR-124 pathways may have potential antidepressant effects. PMID- 27383600 TI - Spontaneous Release Regulates Synaptic Scaling in the Embryonic Spinal Network In Vivo. AB - Homeostatic plasticity mechanisms maintain cellular or network spiking activity within a physiologically functional range through compensatory changes in synaptic strength or intrinsic cellular excitability. Synaptic scaling is one form of homeostatic plasticity that is triggered after blockade of spiking or neurotransmission in which the strengths of all synaptic inputs to a cell are multiplicatively scaled upward or downward in a compensatory fashion. We have shown previously that synaptic upscaling could be triggered in chick embryo spinal motoneurons by complete blockade of spiking or GABAA receptor (GABAAR) activation for 2 d in vivo Here, we alter GABAAR activation in a more physiologically relevant manner by chronically adjusting presynaptic GABA release in vivo using nicotinic modulators or an mGluR2 agonist. Manipulating GABAAR activation in this way triggered scaling in a mechanistically similar manner to scaling induced by complete blockade of GABAARs. Remarkably, we find that altering action-potential (AP)-independent spontaneous release was able to fully account for the observed bidirectional scaling, whereas dramatic changes in spiking activity associated with spontaneous network activity had little effect on quantal amplitude. The reliance of scaling on an AP-independent process challenges the plasticity's relatedness to spiking in the living embryonic spinal network. Our findings have implications for the trigger and function of synaptic scaling and suggest that spontaneous release functions to regulate synaptic strength homeostatically in vivo SIGNIFICANCE STATEMENT: Homeostatic synaptic scaling is thought to prevent inappropriate levels of spiking activity through compensatory adjustments in the strength of synaptic inputs. Therefore, it is thought that perturbations in spike rate trigger scaling. Here, we find that dramatic changes in spiking activity in the embryonic spinal cord have little effect on synaptic scaling; conversely, alterations in GABAA receptor activation due to action-potential-independent GABA vesicle release can trigger scaling. The findings suggest that scaling in the living embryonic spinal cord functions to maintain synaptic strength and challenge the view that scaling acts to regulate spiking activity homeostatically. Finally, the results indicate that fetal exposure to drugs that influence GABA spontaneous release, such as nicotine, could profoundly affect synaptic maturation. PMID- 27383602 TI - Rab35 Functions in Axon Elongation Are Regulated by P53-Related Protein Kinase in a Mechanism That Involves Rab35 Protein Degradation and the Microtubule Associated Protein 1B. AB - Rab35 is a key protein for cargo loading in the recycling endosome. In neuronal immortalized cells, Rab35 promotes neurite differentiation. Here we describe that Rab35 favors axon elongation in rat primary neurons in an activity-dependent manner. In addition, we show that the p53-related protein kinase (PRPK) negatively regulates axonal elongation by reducing Rab35 protein levels through the ubiquitin-proteasome degradation pathway. PRPK-induced Rab35 degradation is regulated by its interaction with microtubule-associated protein 1B (MAP1B), a microtubule stabilizing binding protein essential for axon elongation. Consistently, axon defects found in MAP1B knock-out neurons were reversed by Rab35 overexpression or PRPK inactivation suggesting an epistatic relationship among these proteins. These results define a novel mechanism to support axonal elongation, by which MAP1B prevents PRPK-induced Rab35 degradation. Such a mechanism allows Rab35-mediated axonal elongation and connects the regulation of actin dynamics with membrane trafficking. In addition, our study reveals for the first time that the ubiquitin-proteasome degradation pathway regulates a Rab GTPase. SIGNIFICANCE STATEMENT: Rab35 is required for axonal outgrowth. We define that its protein levels are negatively regulated by p53-related protein kinase (PRPK). We show that microtubule-associated protein 1B (MAP1B) interacts with PRPK, preventing PRPK-dependent Rab35 proteasome degradation. We demonstrate that Rab35 regulates Cdc42 activity in neurons. This is the first evidence showing that a Rab protein is regulated by degradation dependent on the ubiquitin proteasome system. PMID- 27383601 TI - Expression of an Activated Integrin Promotes Long-Distance Sensory Axon Regeneration in the Spinal Cord. AB - After CNS injury, axon regeneration is blocked by an inhibitory environment consisting of the highly upregulated tenascin-C and chondroitin sulfate proteoglycans (CSPGs). Tenascin-C promotes growth of axons if they express a tenascin-binding integrin, particularly alpha9beta1. Additionally, integrins can be inactivated by CSPGs, and this inhibition can be overcome by the presence of a beta1-binding integrin activator, kindlin-1. We examined the synergistic effect of alpha9 integrin and kindlin-1 on sensory axon regeneration in adult rat spinal cord after dorsal root crush and adeno-associated virus transgene expression in dorsal root ganglia. After 12 weeks, axons from C6-C7 dorsal root ganglia regenerated through the tenascin-C-rich dorsal root entry zone into the dorsal column up to C1 level and above (>25 mm axon length) through a normal pathway. Animals also showed anatomical and electrophysiological evidence of reconnection to the dorsal horn and behavioral recovery in mechanical pressure, thermal pain, and ladder-walking tasks. Expression of alpha9 integrin or kindlin-1 alone promoted much less regeneration and recovery. SIGNIFICANCE STATEMENT: The study demonstrates that long-distance sensory axon regeneration over a normal pathway and with sensory and sensory-motor recovery can be achieved. This was achieved by expressing an integrin that recognizes tenascin-C, one of the components of glial scar tissue, and an integrin activator. This enabled extensive long-distance (>25 mm) regeneration of both myelinated and unmyelinated sensory axons with topographically correct connections in the spinal cord. The extent of growth and recovery we have seen would probably be clinically significant. Restoration of sensation to hands, perineum, and genitalia would be a significant improvement for a spinal cord-injured patient. PMID- 27383603 TI - Global Motion Processing in Human Visual Cortical Areas V2 and V3. AB - Global motion perception entails the ability to extract the central direction tendency from an extended area of visual space containing widely disparate local directions. A substantial body of evidence suggests that local motion signals generated in primary visual cortex (V1) are spatially integrated to provide perception of global motion, beginning in the middle temporal area (MT) in macaques and its counterpart in humans, hMT. However, V2 and V3 also contain motion-sensitive neurons that have larger receptive fields than those found in V1, giving the potential for spatial integration of motion signals. Despite this, V2 and V3 have been overlooked as sites of global motion processing. To test, free of local-global confounds, whether human V2 and V3 are important for encoding global motion, we developed a visual stimulus that yields a global direction yet includes all possible local directions and is perfectly balanced at the local motion level. We then attempted to decode global motion direction in such stimuli with multivariate pattern classification of fMRI data. We found strong sensitivity to global motion in hMT, as expected, and also in several higher visual areas known to encode optic flow. Crucially, we found that global motion direction could be decoded in human V2 and, particularly, in V3. The results suggest the surprising conclusion that global motion processing is a key function of cortical visual areas V2 and V3. A possible purpose is to provide global motion signals to V6. SIGNIFICANCE STATEMENT: Humans can readily detect the overall direction of movement in a flock of birds despite large differences in the directions of individual birds at a given moment. This ability to combine disparate motion signals across space underlies many aspects of visual motion perception and has therefore received considerable research attention. The received wisdom is that spatial integration of motion signals occurs in the cortical motion complex MT+ in both human and nonhuman primates. We show here that areas V2 and V3 in humans are also able to perform this function. We suggest that different cortical areas integrate motion signals in different ways for different purposes. PMID- 27383605 TI - Identification of the fatty alcohol oxidase FAO1 from Starmerella bombicola and improved novel glycolipids production in an FAO1 knockout mutant. AB - Alkyl polyglucosides (APGs), which were first commercialized in the 1990s, are mild, non-ionic surfactants comprising fatty alcohols and glucose derived from recyclable starch. APGs have good properties as cleaners, foaming agents, and emulsifiers, and they do not undergo hydrolysis at an alkaline pH. In addition to their advantages over traditional synthetic surfactants, APGs are low-irritant surfactants that are nontoxic and easily degradable in the environment. Thus, APGs are considered to be environmentally friendly surfactants. Starmerella bombicola glycosylates long-chain omega or omega-1 hydroxy fatty acids, and it also directly glycosylates secondary alcohols. Although it is generally difficult to directly glycosylate primary alcohols, they are easily converted to the corresponding fatty acids by S. bombicola because of its strong alcohol oxidase activity. To redirect unconventional substrates toward APG synthesis, the long chain alcohol oxidation pathway was blocked by knocking out the fatty alcohol oxidase gene. The complete sequence of the S. bombicola FAO1 gene (2046 bp) was cloned, and the obtained nucleotide sequence was used to construct a knockout cassette. An FAO1 knockout mutant with the correct genotype and phenotype was evaluated by fermentation on 1-tetradecanol. The mutant produced tetradecyl disaccharides and tetradecanediol tetrasaccharides. The APGs and diol polyglucosides (DPGs) production of the mutant was 27.3 g/L ((APGs + DPGs)/de novo sophorolipids ratio was about 15:1), while the parent strain did not produce APG or DPG. These data indicate that the substrates had been redirected toward novel glycolipids synthesis in the mutant. PMID- 27383604 TI - Fragile X Mental Retardation Protein Is Required to Maintain Visual Conditioning Induced Behavioral Plasticity by Limiting Local Protein Synthesis. AB - Fragile X mental retardation protein (FMRP) is thought to regulate neuronal plasticity by limiting dendritic protein synthesis, but direct demonstration of a requirement for FMRP control of local protein synthesis during behavioral plasticity is lacking. Here we tested whether FMRP knockdown in Xenopus optic tectum affects local protein synthesis in vivo and whether FMRP knockdown affects protein synthesis-dependent visual avoidance behavioral plasticity. We tagged newly synthesized proteins by incorporation of the noncanonical amino acid azidohomoalanine and visualized them with fluorescent noncanonical amino acid tagging (FUNCAT). Visual conditioning and FMRP knockdown produce similar increases in FUNCAT in tectal neuropil. Induction of visual conditioning dependent behavioral plasticity occurs normally in FMRP knockdown animals, but plasticity degrades over 24 h. These results indicate that FMRP affects visual conditioning-induced local protein synthesis and is required to maintain the visual conditioning-induced behavioral plasticity. SIGNIFICANCE STATEMENT: Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. Exaggerated dendritic protein synthesis resulting from loss of fragile X mental retardation protein (FMRP) is thought to underlie cognitive deficits in FXS, but no direct evidence has demonstrated that FMRP-regulated dendritic protein synthesis affects behavioral plasticity in intact animals. Xenopus tadpoles exhibit a visual avoidance behavior that improves with visual conditioning in a protein synthesis-dependent manner. We showed that FMRP knockdown and visual conditioning dramatically increase protein synthesis in neuronal processes. Furthermore, induction of visual conditioning-dependent behavioral plasticity occurs normally after FMRP knockdown, but performance rapidly deteriorated in the absence of FMRP. These studies show that FMRP negatively regulates local protein synthesis and is required to maintain visual conditioning-induced behavioral plasticity in vivo. PMID- 27383606 TI - High pressure-promoted xylanase treatment to enhance papermaking properties of recycled pulp. AB - Industrially produced bleached recycled pulp (R) comprising essentially hardwood fibres was subjected to enzymatic treatment with endo-xylanase from Thermomyces lanuginosus with or without ultra-high hydrostatic pressure (UHP) pre-treatment at 300-600 MPa for 10 min. The kinetics and the extent of enzymatic hydrolysis after UHP pre-treatment under different conditions have been evaluated by released reducing sugars and the analysis of neutral sugars in pulps, respectively. The changes in surface chemical composition of pulps were assessed by UV-vis diffuse reflectance spectroscopy. UHP-pre-treated R under optimal conditions (400 MPa), with or without posterior enzymatic treatment, was used for the production of handsheets and evaluation of its mechanical properties. It was suggested that enzymatic modification improves significantly the papermaking properties of recycled pulp. These improvements were related with selective removal of xylan bound to impurities and to aggregated cellulose fibrils on the fibre surface, thus favouring the ensuing swelling and inter-fibre bonding in paper. UHP pre-treatment and posterior enzymatic treatment revealed a synergetic effect on the mechanical properties of recycled pulp. This fact was assigned to enhanced accessibility of fibres towards xylanase and by forced hydration and favourable rearrangement of cellulosic fibrils in fibres after UHP pre-treatment. The increase of basic strength properties after UHP-promoted xylanase treatment was up to 30 % being the most pronounced for the tensile strength and the burst resistance. PMID- 27383608 TI - Retraction Note To: The nitrile-degrading enzymes: current status and future prospects. PMID- 27383607 TI - Evaluation of a protective effect of in ovo delivered Campylobacter jejuni OMVs. AB - Campylobacter jejuni is the most prevalent cause of a food-borne gastroenteritis in the developed world, with poultry being the main source of infection. Campylobacter jejuni, like other Gram-negative bacteria, constitutively releases outer membrane vesicles (OMVs). OMVs are highly immunogenic, can be taken up by mammalian cells, and are easily modifiable by recombinant engineering. We have tested their usefulness for an oral (in ovo) vaccination of chickens. Four groups of 18-day-old chicken embryos (164 animals) underwent injection of wt C. jejuni OMVs or modified OMVs or PBS into the amniotic fluid. The OMVs modifications relied on overexpression of either a complete wt cjaA gene or the C20A mutant that relocates to the periplasm. Fourteen days post-hatch chicks were orally challenged with live C. jejuni strain. Cecum colonization parameters were analyzed by two-way ANOVA with Tukey post-hoc test. The wtOMVs and OMVs with wtCjaA overexpression were found to confer significant protection of chicken against C. jejuni (p = 0.03 and p = 0.013, respectively) in comparison to PBS controls and are promising candidates for further in ovo vaccine development. PMID- 27383609 TI - Efficient modulation of optical and electrical properties of X-shaped thermally activated delayed fluorescence emitters by substitution. AB - A series of X-shaped thermally activated delayed fluorescence (TADF) emitters are systematically studied by first-principles calculations. Effects of the cyano group adding to the acceptor unit and the hydroxyl group adding to the donor part on the optical and electrical properties are analyzed. It is found that both kinds of groups can efficiently increase the emission wavelength to realize full color emission. Although they play different roles in modulating the energy level of frontier orbitals, the S-T energy gap, the reorganization energy and transfer integral for different molecules, they can efficiently increase the charge transfer rate and reduce the difference of electron transfer rate and hole transfer rate. These results indicate that these designed strategies are efficient to achieve balanced charge transfer rates and modulate emission colors. By analyzing the energy matching between the TADF emitters and three kinds of hosts, the emission spectra of the 3,5-bis(N-carbazolyl)benzene (mcp) and the absorption spectra of most TADF emitters have a large overlap, which provides helpful information in application of these TADF molecules. PMID- 27383610 TI - The inner-induced effects of YCN in C76 on the structures and nonlinear optical properties. AB - Very recently, an unprecedented novel monometallic cluster of fullerenes entrapping a yttrium cyanide (YCN) cluster inside a popular C82 cage YCN@Cs(6) C82 was synthesized and characterized. Inspired by this investigation, four non IPR YCN@C1(17459)-C76, YCN@C2v(19138)-C76, YCN@C2(17646)-C76, and YCN@C1(17894) C76 (1, 2, 3, and 4) containing a pair of adjacent pentagons are designed to explore the encapsulated molecular effect on their interaction energies and nonlinear optical properties. The interaction energy (E int) values of 1, 2, 3, and 4 are -481.35 (1), -477.91 (2), -482.04 (3), -482.69 (4) kcal mol(-1), respectively, which shows that the E int value of 4 is the largest. Furthermore, the electron-transfer is mainly from the YCN to C76 cage. When YCN is encapsulated into C76 cage, we can find that the alpha0 values of the four molecules are very close, ranging from 6.50 * 10(2) to 6.65 * 10(2) au. Significantly, the first hyperpolarizabilities are in relation to the encapsulated molecular: 1.63 * 10(3) (1) > 8.03 * 10(2) (2) > 7.76 * 10(2) (4) > 4.86 * 10(2) au (3), the results show that the betatot value of 1 is the largest. Besides this, the encapsulation of the YCN to C76 cage brings some distinctive changes in its UV-vis spectra along with its other electronic properties that might be used by the experimentalists to develop the potential nonlinear optical nanomaterials based on endohedral metallofullerenes. PMID- 27383611 TI - Van der Waals molecular interactions in the organic functionalization of graphane, silicane, and germanane with alkene and alkyne molecules: a DFT-D2 study. AB - Density functional theory with the addition of a semi-empirical dispersion potential was applied to the conventional Kohn-Sham energy to study the adsorption of alkene and alkyne molecules on hydrogen-terminated two-dimensional group IV systems (graphane, silicane, and germanane) by means of a radical initiated reaction. In particular, we investigated the interactions of acetylene, ethylene, and styrene with those surfaces. Although we had studied these systems previously, we included van der Waals interactions in all of the cases examined in the present work. These forces, which are noncovalent interactions, can heavily influence different processes in molecular chemistry, such as the adsorption of organic molecules on semiconductor surfaces. This unified approach allowed us to perform a comparative study of the relative reactivities of the various organic molecule/surface systems. The results showed that the degree of covalency of the surface, the lattice size, and the partial charge distribution (caused by differences in electronegativity) are all key elements that determine the reactivity between the molecules and the surfaces tested in this work. The covalent nature of graphane gives rise to energetically favorable intermediate states, while the opposite polarities of the charge distributions of silicane and germanane with the organic molecules favor subsequent steps of the radical initiated reaction. Finally, the lattice size is a factor that has important consequences due to steric effects present in the systems and the possibility of chain reaction continuation. The results obtained in this work show that careful selection of the substrate is very important. Calculated energy barriers, heats of adsorption, and optimized atomic structures show that the silicane system offers the best reactivity in organic functionalization. PMID- 27383612 TI - Single Muscle Immobilization Decreases Single-Fibre Myosin Heavy Chain Polymorphism: Possible Involvement of p38 and JNK MAP Kinases. AB - PURPOSE: Muscle contractile phenotype is affected during immobilization. Myosin heavy chain (MHC) isoforms are the major determinant of the muscle contractile phenotype. We therefore sought to evaluate the effects of muscle immobilization on both the MHC composition at single-fibre level and the mitogen-activated protein kinases (MAPK), a family of intracellular signaling pathways involved in the stress-induced muscle plasticity. METHODS: The distal tendon of female Wistar rat Peroneus Longus (PL) was cut and fixed to the adjacent bone at neutral muscle length. Four weeks after the surgery, immobilized and contralateral PL were dissociated and the isolated fibres were sampled to determine MHC composition. Protein kinase 38 (p38), extracellular signal-regulated kinases (ERK1/2), and c Jun- NH2-terminal kinase (JNK) phosphorylations were measured in 6- and 15-day immobilized and contralateral PL. RESULTS: MHC distribution in immobilized PL was as follows: I = 0%, IIa = 11.8 +/- 2.8%, IIx = 53.0 +/- 6.1%, IIb = 35.3 +/- 7.3% and I = 6.1 +/- 3.9%, IIa = 22.1 +/- 3.4%, IIx = 46.6 +/- 4.5%, IIb = 25.2 +/- 6.6% in contralateral muscle. The MHC composition in immobilized muscle is consistent with a faster contractile phenotype according to the Hill's model of the force-velocity relationship. Immobilized and contralateral muscles displayed a polymorphism index of 31.1% (95% CI 26.1-36.0) and 39.3% (95% CI 37.0-41.5), respectively. Significant increases in p38 and JNK phosphorylation were observed following 6 and 15 days of immobilization. CONCLUSIONS: Single muscle immobilization at neutral length induces a shift of MHC composition toward a faster contractile phenotype and decreases the polymorphic profile of single fibres. Activation of p38 and JNK could be a potential mechanism involved in these contractile phenotype modifications during muscle immobilization. PMID- 27383613 TI - Psychotropic Drug Consumption and Employment Status in Time of Economic Crisis (2007-2011). AB - Psychiatric disorders and in particular depression have increased during the "Great Recession". The aim of this study was to investigate the consumption of psychotropic drugs in people who lost their permanent employment, using administrative data. The study considered all of the subjects domiciled in Lombardy, Northern Italy, who lost a permanent employment between 2008 and 2010, not assuming psychotropic drugs and who did not find a new job within the following 12 months. The control group included people who did not lose permanent job in the study period, matched to the cases for gender, age, nationality, skill level, education and economic sector, using propensity score matching. The subjects who lost their permanent employment were 17 % more likely to receive one or more drug prescriptions than the controls, but the difference was significant only for males. Females, subjects aged >50 years, low skill level workers and Italians were more likely to have received a prescription for psychotropic drugs than respectively males, subjects aged 20-29 years or aged 30-39 years, low skill level workers and non-Italians. The average number of drugs prescribed for those who lost their job and those who continued working was respectively 2.9 and 3.1. In conclusion, losing a permanent job increases significantly psychotropic drugs consumption in males but not in females. PMID- 27383614 TI - Structure of Mesophotic Reef Fish Assemblages in the Northwestern Hawaiian Islands. AB - Mesophotic coral ecosystems (MCEs) support diverse communities of marine organisms with changes in community structure occurring along a depth gradient. In recent years, MCEs have gained attention due to their depths that provide protection from natural and anthropogenic stressors and their relative stability over evolutionary time periods, yet ecological structures of fish assemblages in MCEs remain largely un-documented. Here, we investigated composition and trophic structure of reef fish assemblages in the Northwestern Hawaiian Islands (NWHI) along a depth gradient from 1 to 67 m. The structure of reef fish assemblages as a whole showed a clear gradient from shallow to mesophotic depths. Fish assemblages at mesophotic depths had higher total densities than those in shallower waters, and were characterized by relatively high densities of planktivores and invertivores and relatively low densities of herbivores. Fishes that typified assemblages at mesophotic depths included six species that are endemic to the Hawaiian Islands. The present study showed that mesophotic reefs in the NWHI support unique assemblages of fish that are characterized by high endemism and relatively high densities of planktivores. Our findings underscore the ecological importance of these undersurveyed ecosystems and warrant further studies of MCEs. PMID- 27383615 TI - Oesophageal lumen pH in yearling horses and effects of management and administration of omeprazole. AB - BACKGROUND: In human subjects, arytenoid chondritis can be caused by chemical trauma of mucosa attributable to gastro-oesophageal reflux. Although a similar process may be involved in the aetiopathogenesis of arytenoid chondritis in horses, the oesophageal lumen pH in this species is poorly understood. OBJECTIVES: To determine if gastro-oesophageal reflux occurs in horses by characterising oesophageal lumen pH. STUDY DESIGN: Blinded, randomised, placebo controlled, crossover, experimental study. METHODS: Luminal oesophageal pH in six yearling horses was recorded over four 24 h periods using an ambulatory pH recorder attached to a catheter with two electrodes (proximal and distal) inserted into the oesophagus. Recordings of pH were made during three management protocols. Initially, horses grazed in a paddock (Protocol A). Horses were then moved to stables to simulate sale preparation of Thoroughbred yearlings, and were given either omeprazole (Protocol B) or placebo paste (Protocol C) orally once per day. Protocol A was repeated for each horse (after a 13 day washout period) between Protocols B and C. Summary statistics described pH range and frequency of pH changes. Associations with predictor variables were investigated using linear mixed-effects models. Data are presented as the mean +/- s.d. RESULTS: Oesophageal lumen pH ranged from 4.90 to 9.70 (7.36 +/- 0.27 and 7.18 +/- 0.24 for the proximal and distal electrodes, respectively) and varied frequently (1.2 +/- 0.9 changes/min and 0.8 +/- 0.8 changes/min for the proximal and distal electrodes, respectively). Oesophageal lumen pH was associated with time since concentrate feeding, activity and time of day, but not with treatment of omeprazole. MAIN LIMITATIONS: A small number of horses were used and measurement periods were limited. CONCLUSIONS: Gastro-oesophageal reflux occurs in clinically normal yearling horses. Although omeprazole had no detectable effect, oesophageal lumen pH recorded during this study did not fall within the therapeutic range of omeprazole. PMID- 27383616 TI - Telling in-tune from out-of-tune: widespread evidence for implicit absolute intonation. AB - Absolute pitch (AP) is the rare ability to name or produce an isolated musical note without the aid of a reference note. One skill thought to be unique to AP possessors is the ability to provide absolute intonation judgments (e.g., classifying an isolated note as "in-tune" or "out-of-tune"). Recent work has suggested that absolute intonation perception among AP possessors is not crystallized in a critical period of development, but is dynamically maintained by the listening environment, in which the vast majority of Western music is tuned to a specific cultural standard. Given that all listeners of Western music are constantly exposed to this specific cultural tuning standard, our experiments address whether absolute intonation perception extends beyond AP possessors. We demonstrate that non-AP listeners are able to accurately judge the intonation of completely isolated notes. Both musicians and nonmusicians showed evidence for absolute intonation recognition when listening to familiar timbres (piano and violin). When testing unfamiliar timbres (triangle and inverted sine waves), only musicians showed weak evidence of absolute intonation recognition (Experiment 2). Overall, these results highlight a previously unknown similarity between AP and non-AP possessors' long-term musical note representations, including evidence of sensitivity to frequency. PMID- 27383617 TI - Rhythm histograms and musical meter: A corpus study of Malian percussion music. AB - Studies of musical corpora have given empirical grounding to the various features that characterize particular musical styles and genres. Palmer & Krumhansl (1990) found that in Western classical music the likeliest places for a note to occur are the most strongly accented beats in a measure, and this was also found in subsequent studies using both Western classical and folk music corpora (Huron & Ommen, 2006; Temperley, 2010). We present a rhythmic analysis of a corpus of 15 performances of percussion music from Bamako, Mali. In our corpus, the relative frequency of note onsets in a given metrical position does not correspond to patterns of metrical accent, though there is a stable relationship between onset frequency and metrical position. The implications of this non-congruence between simple statistical likelihood and metrical structure for the ways in which meter and metrical accent may be learned and understood are discussed, along with importance of cross-cultural studies for psychological research. PMID- 27383618 TI - The influence of 2-hop network density on spoken word recognition. AB - The influence of 2-hop density on spoken word recognition was investigated. 2-hop density measures the density of connections among the phonological neighbors (i.e., 1-hop neighbors) and phonological neighbors of those neighbors (i.e., 2 hop neighbors) of a target word. In both naming and lexical decision tasks, words with low 2-hop density were recognized more quickly than words with high 2-hop density. Because stimuli were selected such that the number of 1-hop and 2-hop neighbors were matched across both sets of words, the results suggest that spoken word recognition is influenced by the amount of connectivity among distant neighbors of the target word-a result that is not easily accommodated by current models of spoken word recognition. A diffusion of activation framework is proposed to account for the present findings. PMID- 27383619 TI - What's she doing in the kitchen? Context helps when actions are hard to recognize. AB - Specific spatial environments are often indicative of where certain actions may take place: In kitchens we prepare food, and in bathrooms we engage in personal hygiene, but not vice versa. In action recognition, contextual cues may constrain an observer's expectations toward actions that are more strongly associated with a particular context than others. Such cues should become particularly helpful when the action itself is difficult to recognize. However, to date only easily identifiable actions were investigated, and the effects of context on recognition were rather interfering than facilitatory. To test whether context also facilitates action recognition, we measured recognition performance of hardly identifiable actions that took place in compatible, incompatible, and neutral contextual settings. Action information was degraded by pixelizing the area of the object manipulation while the room in which the action took place remained fully visible. We found significantly higher accuracy for actions that took place in compatible compared to incompatible and neutral settings, indicating facilitation. Additionally, action recognition was slower in incompatible settings than in compatible and neutral settings, indicating interference. Together, our findings demonstrate that contextual information is effectively exploited during action observation, in particular when visual information about the action itself is sparse. Differential effects on speed and accuracy suggest that contexts modulate action recognition at different levels of processing. Our findings emphasize the importance of contextual information in comprehensive, ecologically valid models of action recognition. PMID- 27383620 TI - Climate, Environment and Early Human Innovation: Stable Isotope and Faunal Proxy Evidence from Archaeological Sites (98-59ka) in the Southern Cape, South Africa. AB - The Middle Stone Age (MSA) of southern Africa, and in particular its Still Bay and Howiesons Poort lithic traditions, represents a period of dramatic subsistence, cultural, and technological innovation by our species, Homo sapiens. Climate change has frequently been postulated as a primary driver of the appearance of these innovative behaviours, with researchers invoking either climate instability as a reason for the development of buffering mechanisms, or environmentally stable refugia as providing a stable setting for experimentation. Testing these alternative models has proved intractable, however, as existing regional palaeoclimatic and palaeoenvironmental records remain spatially, stratigraphically, and chronologically disconnected from the archaeological record. Here we report high-resolution records of environmental shifts based on stable carbon and oxygen isotopes in ostrich eggshell (OES) fragments, faunal remains, and shellfish assemblages excavated from two key MSA archaeological sequences, Blombos Cave and Klipdrift Shelter. We compare these records with archaeological material remains in the same strata. The results from both sites, spanning the periods 98-73 ka and 72-59 ka, respectively, show significant changes in vegetation, aridity, rainfall seasonality, and sea temperature in the vicinity of the sites during periods of human occupation. While these changes clearly influenced human subsistence strategies, we find that the remarkable cultural and technological innovations seen in the sites cannot be linked directly to climate shifts. Our results demonstrate the need for scale appropriate, on-site testing of behavioural-environmental links, rather than broader, regional comparisons. PMID- 27383621 TI - Patient specific 3D print of left atrial appendage for closure device. PMID- 27383623 TI - Junior doctor contract will be imposed, says Hunt. PMID- 27383622 TI - Are Randomized Controlled Trials the (G)old Standard? From Clinical Intelligence to Prescriptive Analytics. AB - Despite the accelerating pace of scientific discovery, the current clinical research enterprise does not sufficiently address pressing clinical questions. Given the constraints on clinical trials, for a majority of clinical questions, the only relevant data available to aid in decision making are based on observation and experience. Our purpose here is 3-fold. First, we describe the classic context of medical research guided by Poppers' scientific epistemology of "falsificationism." Second, we discuss challenges and shortcomings of randomized controlled trials and present the potential of observational studies based on big data. Third, we cover several obstacles related to the use of observational (retrospective) data in clinical studies. We conclude that randomized controlled trials are not at risk for extinction, but innovations in statistics, machine learning, and big data analytics may generate a completely new ecosystem for exploration and validation. PMID- 27383624 TI - Optimization of two-compartment-exchange-model analysis for dynamic contrast enhanced mri incorporating bolus arrival time. AB - PURPOSE: To optimize the analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) under the two-compartment-exchange-model (2CXM) and to incorporate voxelwise bolus-arrival-time (BAT). MATERIALS AND METHODS: The accuracy of the pharmacokinetic (PK) parameters, extracted from 3T DCE-MRI using 2CXM, was tested under several conditions: eight algorithms for data estimation; correction for BAT; using model selection; different temporal resolution and scan duration. Comparisons were performed on simulated data. The best algorithm was applied to seven patients with brain tumors or following stroke. The extracted perfusion parameters were compared to those of dynamic susceptibility contrast MRI (DSC-MRI). RESULTS: ACoPeD (AIF-corrected-perfusion-DCE-MRI), an analysis using a 2nd derivative regularized-spline and incorporating BAT, achieved the most accurate estimation in simulated data, mean-relative-error: Fp , F, vp , ve : 24.8%, 41.7%, 26.4%, 27.2% vs. 76.5%, 190.8%, 78.8%, 82.39% of the direct four parameters estimation (one-sided two-sample t-test, P < 0.001). Correction for BAT increased the estimation accuracy of the PK parameters by more than 30% and provided a supertemporal resolution estimation of the BAT (higher than the acquired resolution, mean-absolute-error 0.2 sec). High temporal resolution (~2 sec) is required to avoid biased estimation of PK parameters, and long scan duration (~20 min) is important for reliable permeability but not for perfusion estimations, mean-error-reduction: E: ~12%, ve : ~6%. Using ACoPeD, PK values from normal-appearing white matter, gray matter, and lesion were extracted from patients. Preliminary results showed significant voxelwise correlations to DSC MRI, between flow values in a patient following stroke (r = 0.49, P < 0.001), and blood volume in a patient with a brain tumor (r = 0.62, P < 0.001). CONCLUSION: This study proposes an optimized analysis method, ACoPeD, for tissue perfusion and permeability estimation using DCE-MRI, to be used in clinical settings. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:237-249. PMID- 27383625 TI - Phenol-soluble modulin alpha4 mediates Staphylococcus aureus-associated vascular leakage by stimulating heparin-binding protein release from neutrophils. AB - Vascular leakage frequently occurs in patients with severe Staphylococcus aureus infection. However, the mechanism underlying S. aureus infection-induced vascular leakage remains unclear. Here, we identified the S. aureus virulence factor phenol-soluble modulin (PSM)alpha4 from the culture supernatant of strain USA300 as a stimulator of heparin-binding protein (HBP) release from polymorphonuclear neutrophils (PMNs) and demonstrated that PSMalpha4-induced HBP release from PMNs leads to vascular leakage. PSMalpha4 appeared less cytolytic than PSMalpha1-3 and was insensitive to lipoproteins; it significantly increased myeloperoxidase and elastase release from PMNs and cell surface CD63 expression in PMNs. PSMalpha4 induced HBP release required formyl peptide receptor 2 (FPR2) and phosphoinositide 3-kinase (PI3K) and depended on Ca(2+) influx and cytoskeleton rearrangement. Thus, PSMalpha4 may stimulate HBP release by activating FPR2 and PI3K to initiate PMN degranulation. PSMalpha4-induced HBP release from PMNs increased endothelial cell monolayer permeability in vitro and induced vascular leakage in mice. This novel function of PSMalpha4 may contribute to the pathogenesis of S. aureus and may be a potential therapeutic target. PMID- 27383626 TI - Sterol metabolism in the filasterean Capsaspora owczarzaki has features that resemble both fungi and animals. AB - Sterols are essential for several physiological processes in most eukaryotes. Sterols regulate membrane homeostasis and participate in different signalling pathways not only as precursors of steroid hormones and vitamins, but also through its role in the formation of lipid rafts. Two major types of sterols, cholesterol and ergosterol, have been described so far in the opisthokonts, the clade that comprise animals, fungi and their unicellular relatives. Cholesterol predominates in derived bilaterians, whereas ergosterol is what generally defines fungi. We here characterize, by a combination of bioinformatic and biochemical analyses, the sterol metabolism in the filasterean Capsaspora owczarzaki, a close unicellular relative of animals that is becoming a model organism. We found that C. owczarzaki sterol metabolism combines enzymatic activities that are usually considered either characteristic of fungi or exclusive to metazoans. Moreover, we observe a differential transcriptional regulation of this metabolism across its life cycle. Thus, C. owczarzaki alternates between synthesizing 7 dehydrocholesterol de novo, which happens at the cystic stage, and the partial conversion-via a novel pathway-of incorporated cholesterol into ergosterol, the characteristic fungal sterol, in the filopodial and aggregative stages. PMID- 27383627 TI - Virion encapsidated HIV-1 Vpr induces NFAT to prime non-activated T cells for productive infection. AB - The majority of T cells encountered by HIV-1 are non-activated and do not readily allow productive infection. HIV-1 Vpr is highly abundant in progeny virions, and induces signalling and HIV-1 LTR transcription. We hence hypothesized that Vpr might be a determinant of non-activated T-cell infection. Virion-delivered Vpr activated nuclear factor of activated T cells (NFAT) through Ca(2+) influx and interference with the NFAT export kinase GSK3beta. This leads to NFAT translocation and accumulation within the nucleus and was required for productive infection of unstimulated primary CD4(+) T cells. A mutagenesis approach revealed correlation of Vpr-mediated NFAT activation with its ability to enhance LTR transcription and mediate cell cycle arrest. Upon NFAT inhibition, Vpr did not augment resting T-cell infection, and showed reduced G2/M arrest and LTR transactivation. Altogether, Vpr renders unstimulated T cells more permissive for productive HIV-1 infection and stimulates activation of productively infected as well as virus-exposed T cells. Therefore, it could be involved in the establishment and reactivation of HIV-1 from viral reservoirs and might have an impact on the levels of immune activation, which are determinants of HIV-1 pathogenesis. PMID- 27383628 TI - A single amino acid substitution in a chitinase of the legume Medicago truncatula is sufficient to gain Nod-factor hydrolase activity. AB - The symbiotic interaction between nitrogen-fixing rhizobia and legumes depends on lipo-chitooligosaccharidic Nod-factors (NFs). The NF hydrolase MtNFH1 of Medicago truncatula is a symbiotic enzyme that hydrolytically inactivates NFs with a C16 : 2 acyl chain produced by the microsymbiont Sinorhizobium meliloti 1021. MtNFH1 is related to class V chitinases (glycoside hydrolase family 18) but lacks chitinase activity. Here, we investigated the substrate specificity of MtNFH1-related proteins. MtCHIT5a and MtCHIT5b of M. truncatula as well as LjCHIT5 of Lotus japonicus showed chitinase activity, suggesting a role in plant defence. The enzymes failed to hydrolyse NFs from S. meliloti. NFs from Rhizobium leguminosarum with a C18 : 4 acyl moiety were neither hydrolysed by these chitinases nor by MtNFH1. Construction of chimeric proteins and further amino acid replacements in MtCHIT5b were performed to identify chitinase variants that gained the ability to hydrolyse NFs. A single serine-to-proline substitution was sufficient to convert MtCHIT5b into an NF-cleaving enzyme. MtNFH1 with the corresponding proline-to-serine substitution failed to hydrolyse NFs. These results are in agreement with a substrate-enzyme model that predicts NF cleavage when the C16 : 2 moiety is placed into a distinct fatty acid-binding cleft. Our findings support the view that MtNFH1 evolved from the ancestral MtCHIT5b by gene duplication and subsequent symbiosis-related neofunctionalization. PMID- 27383629 TI - Nrf2 signalling and autophagy are involved in diabetes mellitus-induced defects in the development of mouse placenta. AB - It is widely accepted that diabetes mellitus impairs placental development, but the mechanism by which the disease operates to impair development remains controversial. In this study, we demonstrated that pregestational diabetes mellitus (PGDM)-induced defects in placental development in mice are mainly characterized by the changes of morphological structure of placenta. The alteration of differentiation-related gene expressions in trophoblast cells rather than cell proliferation/apoptosis is responsible for the phenotypes found in mouse placenta. Meanwhile, excess reactive oxygen species (ROS) production and activated nuclear factor erythroid2-related factor 2 (Nrf2) signalling were observed in the placenta of mice suffering from PGDM. Using BeWo cells, we also demonstrated that excess ROS was produced and Nrf2 signalling molecules were activated in settings characterized by a high concentration of glucose. More interestingly, differentiation-related gene expressions in trophoblast cells were altered when endogenous Nrf2 expression is manipulated by transfecting Nrf2-wt or Nrf2-shRNA. In addition, PGDM interferes with autophagy in both mouse placenta and BeWo cells, implying that autophagy is also involved, directly or indirectly, in PGDM-induced placental phenotypes. Therefore, we revealed that dysfunctional oxidative stress-activated Nrf2 signalling and autophagy are probably responsible for PGDM-induced defects in the placental development of mice. The mechanism was through the interference with differentiation-related gene expression in trophoblast cells. PMID- 27383631 TI - Room temperature synthesis of ultra-small, near-unity single-sized lead halide perovskite quantum dots with wide color emission tunability, high color purity and high brightness. AB - Phosphor with extremely narrow emission line widths, high brightness, and wide color emission tunability in visible regions is required for display and lighting applications, yet none has been reported in the literature so far. In the present study, single-sized lead halide perovskite (APbX 3; A = CH3NH3 and Cs; X = Cl, Br, and I) nanocrystalline (NC) phosphors were achieved for the first time in a one-pot reaction at room temperature (25 degrees C). The size-dependent samples, which included four families of CsPbBr3 NCs and exhibited sharp excitonic absorption peaks and pure band gap emission, were directly obtained by simply varying the concentration of ligands. The continuity of the optical spectrum can be successively tuned over the entire UV-visible spectral region (360-610 nm) by preparing CsPbCl3, CsPbI3, and CsPb(Y/Br)3 (Y = Cl and I) NCs with the use of CsPbBr3 NCs as templates by anion exchange while maintaining the size of NCs and high quantum yields of up to 80%. Notably, an emission line width of 10-24 nm, which is completely consistent with that of their single particles, indicates the formation of single-sized NCs. The versatility of the synthetic strategy was validated by extending it to the synthesis of single-sized CH3NH3PbX 3 NCs by simply replacing the cesium precursor by the CH3NH3 X precursor. PMID- 27383630 TI - Combined structural, biochemical and cellular evidence demonstrates that both FGDF motifs in alphavirus nsP3 are required for efficient replication. AB - Recent findings have highlighted the role of the Old World alphavirus non structural protein 3 (nsP3) as a host defence modulator that functions by disrupting stress granules, subcellular phase-dense RNA/protein structures formed upon environmental stress. This disruption mechanism was largely explained through nsP3-mediated recruitment of the host G3BP protein via two tandem FGDF motifs. Here, we present the 1.9 A resolution crystal structure of the NTF2-like domain of G3BP-1 in complex with a 25-residue peptide derived from Semliki Forest virus nsP3 (nsP3-25). The structure reveals a poly-complex of G3BP-1 dimers interconnected through the FGDF motifs in nsP3-25. Although in vitro and in vivo binding studies revealed a hierarchical interaction of the two FGDF motifs with G3BP-1, viral growth curves clearly demonstrated that two intact FGDF motifs are required for efficient viral replication. Chikungunya virus nsP3 also binds G3BP dimers via a hierarchical interaction, which was found to be critical for viral replication. These results highlight a conserved molecular mechanism in host cell modulation. PMID- 27383633 TI - NEWS AND NOTES-SUMMER 2016. PMID- 27383634 TI - Editorial. PMID- 27383632 TI - Interleukin-6 Induces Vascular Endothelial Growth Factor-C Expression via Src-FAK STAT3 Signaling in Lymphatic Endothelial Cells. AB - Elevated serum interleukin-6 (IL-6) levels correlates with tumor grade and poor prognosis in cancer patients. IL-6 has been shown to promote tumor lymphangiogenesis through vascular endothelial growth factor-C (VEGF-C) induction in tumor cells. We recently showed that IL-6 also induced VEGF-C expression in lymphatic endothelial cells (LECs). However, the signaling mechanisms involved in IL-6-induces VEGF-C induction in LECs remain incompletely understood. In this study, we explored the causal role of focal adhesion kinase (FAK) in inducing VEGF-C expression in IL-6-stimulated murine LECs (SV-LECs). FAK signaling blockade by NSC 667249 (a FAK inhibitor) attenuated IL-6-induced VEGF-C expression and VEGF-C promoter-luciferase activities. IL-6's enhancing effects of increasing FAK, ERK1/2, p38MAPK, C/EBPbeta, p65 and STAT3 phosphorylation as well as C/EBPbeta-, kappaB- and STAT3-luciferase activities were reduced in the presence of NSC 667249. STAT3 knockdown by STAT3 siRNA abrogated IL-6's actions in elevating VEGF-C mRNA and protein levels. Moreover, Src-FAK signaling blockade reduced IL-6's enhancing effects of increasing STAT3 binding to the VEGF-C promoter region, cell migration and endothelial tube formation of SV-LECs. Together these results suggest that IL-6 increases VEGF-C induction and lymphangiogenesis may involve, at least in part, Src-FAK-STAT3 cascade in LECs. PMID- 27383635 TI - Communication and support from health-care professionals to families, with dependent children, following the diagnosis of parental life-limiting illness: A systematic review. AB - BACKGROUND: Communication between parents and their children about parental life limiting illness is stressful. Parents want support from health-care professionals; however, the extent of this support is not known. Awareness of family's needs would help ensure appropriate support. AIM: To find the current literature exploring (1) how parents with a life-limiting illness, who have dependent children, perceive health-care professionals' communication with them about the illness, diagnosis and treatments, including how social, practical and emotional support is offered to them and (2) how this contributes to the parents' feelings of supporting their children. DESIGN: A systematic literature review and narrative synthesis. DATA SOURCES: Embase, MEDLINE, PsycINFO, CINAHL and ASSIA ProQuest were searched in November 2015 for studies assessing communication between health-care professionals and parents about how to talk with their children about the parent's illness. RESULTS: There were 1342 records identified, five qualitative studies met the inclusion criteria (55 ill parents, 11 spouses/carers, 26 children and 16 health-care professionals). Parents wanted information from health-care professionals about how to talk to their children about the illness; this was not routinely offered. Children also want to talk with a health-care professional about their parents' illness. Health-care professionals are concerned that conversations with parents and their children will be too difficult and time-consuming. CONCLUSION: Parents with a life limiting illness want support from their health-care professionals about how to communicate with their children about the illness. Their children look to health care professionals for information about their parent's illness. Health-care professionals, have an important role but appear reluctant to address these concerns because of fears of insufficient time and expertise. PMID- 27383636 TI - Implementing a patient-centred outcome measure in daily routine in a specialist palliative care inpatient hospital unit: An observational study. AB - BACKGROUND: Gathering clinical evidence data on patients' palliative care needs is paramount to identify changes in outcomes over time and maintaining on-going quality improvement. Implementation of patient-centred outcome measures has been widely recommended. The routine use of these instruments in daily practice is challenging and not widespread. AIM: To implement a patient-centred outcome measure in daily practice and fulfil one quality indicator: improve pain during the 72 h after admission, in at least 75% of patients. DESIGN: An observational prospective study. The Palliative care Outcome Scale was used at admission (T0), third day (T1) and weekly. SETTING/PARTICIPANTS: Hospital palliative care unit with 17 individual rooms. All patients admitted to the unit were included in the study. RESULTS: Preliminary results ( N = 84) revealed inconsistent and missing data (14%). Symptoms were sub-optimally controlled by T1. Processes changed, and only a team member could apply Palliative care Outcome Scale. Doctors were encouraged to grasp the meaning of Palliative care Outcome Scale results for each patient. The post-pilot included 317 patients. No missing data occurred. There was an improvement in most items between T0 and T1: 'pain' and 'other symptoms' presented statistical significant differences ( p < 0.05). CONCLUSION: Implementing a patient-centred outcome measure in a hospital palliative care service is feasible and improves quality of care. Controlling high pain at T0 improved (>80%) by T1. Results became more consistent and symptom control was improved overall. Patients are evaluated based on holistic domains by an interdisciplinary team and we have added a much needed measure to help guide improvement of the quality of care provided. PMID- 27383637 TI - Transition of adult T-cell leukemia/lymphoma clones during clinical progression. AB - Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm caused by the transformation of HTLV-1-infected T cells. ATLL, especially its aggressive form, is known for its poor prognosis, even with intensive chemotherapy. ATLL cells are considered to be monoclonal; however, multiclonal proliferation or emergence of a new clone over time has been reported based on Southern blot analysis, although direct molecular evidence remains elusive. Furthermore, it is thought that clonal change may be a cause of early drug resistance in ATLL. To directly analyze potential clonal changes in ATLL during its clinical course, we used inverse PCR to detect integration sites in combination with a newly developed method using next-generation sequencing, and compared ATLL cell clonality at different time points. The results of inverse PCR indicated that the major clone was altered in three of 19 patients. Together with results from five patients, using this new method, we found direct evidence of clonal change occurring during the clinical course or in response to chemotherapy in ATLL. These results also highlight the importance of clonality analysis for understanding the mechanisms of ATLL development and drug resistance. PMID- 27383638 TI - Synthesis of Dihydropyrrolizine and Tetrahydroindolizine Scaffolds from Pyrroles by Titanocene(III) Catalysis. AB - A synthetic approach to dihydropyrrolizine and tetrahydroindolizine scaffolds from pyrroles has been developed. The key step, a titanocene(III)-catalyzed radical arylation that proceeds by C-H functionalization is atom-economical and tolerates a large variety of functional groups. The reaction is therefore attractive for the swift assembly of functional and structural diversity. PMID- 27383639 TI - Poly(propylene fumarate)/Polyethylene Glycol-Modified Graphene Oxide Nanocomposites for Tissue Engineering. AB - Poly(propylene fumarate) (PPF)-based nanocomposites incorporating different amounts of polyethylene glycol-functionalized graphene oxide (PEG-GO) have been prepared via sonication and thermal curing, and their surface morphology, structure, thermal stability, hydrophilicity, water absorption, biodegradation, cytotoxicity, mechanical, viscoelastic and antibacterial properties have been investigated. SEM and TEM images corroborated that the noncovalent functionalization with PEG caused the exfoliation of GO into thinner flakes. IR spectra suggested the presence of strong hydrogen-bonding interactions between the nanocomposite components. A gradual rise in the level of hydrophilicity, water uptake, biodegradation rate, surface roughness, protein absorption capability and thermal stability was found upon increasing GO concentration in the composites. Tensile tests revealed improved stiffness, strength and toughness for the composites compared to unfilled PPF, ascribed to a homogeneous GO dispersion within the matrix along with a strong PPF/PEG-GO interfacial adhesion via polar and hydrogen bonding interactions. Further, the nanocomposites retained enough stiffness and strength under a biological state to provide effective support for bone tissue formation. The antibacterial activity was investigated against Gram-positive Staphylococcus aureus and Staphylococcus epidermidis as well as Gram-negative Pseudomonas aeruginosa and Escherichia coli microorganisms, and it rose sharply upon increasing GO concentration; systematically, the biocide effect was stronger versus Gram-positive bacteria. Cell viability data demonstrated that PPF/PEG-GO composites do not induce toxicity over human dermal fibroblasts. These novel materials show great potential to be applied in the bone tissue engineering field. PMID- 27383640 TI - Georges Guillain (1876-1961). PMID- 27383642 TI - Visual height intolerance and acrophobia: distressing partners for life. AB - The course of illness, the degree of social impairment, and the rate of help seeking behavior was evaluated in a sample of individuals with visual height intolerance (vHI) and acrophobia. On the basis of a previously described epidemiological sample representative of the German general population, 574 individuals with vHI were identified, 128 fulfilled the DSM-5 diagnostic criteria of acrophobia. The illness of the majority of all susceptible individuals with vHI ran a year-long chronic course. Two thirds were in the category "persistent/worse", whereas only one third was in the category "improved/remitted". Subjects with acrophobia showed significantly more traumatic triggers of onset, more signs of generalization to other height stimuli, higher rates of increasing intensity of symptom load, higher grades of social impairment, and greater overall negative impact on the quality of life than those with pure vHI. An unfavorable course of illness in pure vHI was predicted by major depression, agoraphobia, social phobia, posttraumatic stress, initial traumatic trigger, and female sex; an unfavorable course in acrophobia was predicted by major depression, chronic fatigue, panic attacks, initial traumatic trigger, social phobia, other specific phobic fears, and female sex. Help-seeking behavior was astonishingly low in the overall sample of individuals with vHI. The consequences of therapeutic interventions if complied with at all were quite modest. In adults pure vHI and even more so acrophobia are by no means only transitionally distressing states. In contrast to their occurrence in children they are more often persisting and disabling conditions. Both the utilization of and adequacy of treatment of these illnesses pose major challenges within primary and secondary neurological and psychiatric medical care. PMID- 27383641 TI - Clinical manifestations in children and adolescents with corpus callosum abnormalities. AB - Corpus callosum abnormality (CCA) outcomes are quite unpredictable and variable, from asymptomatic forms to mild or severe neurodevelopment disorders. The aim of this study was to examine clinical outcomes in CCA patients. The study included 61 children and adolescents in whom brain magnetic resonance imaging (MRI) scans showed CCA, isolated or associated to other central nervous system lesions. All patients underwent anamnesis, physical and neurological examination, routine laboratory tests, electroencephalogram (EEG), and MRI scans. In all participants, the intelligence quotient (IQ) was determined. We divided the participants into two subgroups: the first subgroup included patients with an isolated CCA, and the second subgroup included patients with CCA associated with extra-callosal brain lesions (complex CCA). We found that CCA were associated with elevated frequency to intellectual disability (ID), other neurodevelopment disorders, epilepsy, and isolated EEG anomalies. Mild ID (p = 0.003) was more frequent in the isolated subgroup, while epilepsy (p = 0.036) and pre-perinatal risk factors (p = 0.023) were more frequent in the complex CCA subgroup. Although the role of the CC in the interhemispheric communication is known, neurological and neurodevelopment outcomes of CCA are extremely variable and unpredictable. The presence of extra callosal brain anomalies is one of the major prognostic factor, and probably, they have an important impact on the clinical outcome. PMID- 27383643 TI - Safety and efficacy of botulinum toxin A for the treatment of spasticity in amyotrophic lateral sclerosis: results of a pilot study. AB - Spasticity can be a very disabling problem in some amyotrophic lateral sclerosis (ALS) phenotypes, such as upper motor neuron-dominant ALS (UMN-D ALS) and primary lateral sclerosis (PLS). Our aim is to describe the safety and efficacy of botulinum toxin A (BoTox-A) for improving gait in those ALS phenotypes. UMN-D ALS and PLS outpatients experiencing gait disturbances, secondary to moderate-to severe spasticity despite optimized oral medication, were offered BoTox-A treatment. Stretching exercises were indicated to complement BoTox-A effect, and ankle-foot orthotics were prescribed when appropriate. Tolerance (muscle strength, disease progression rate) and efficacy (10-m walk test) were measured at baseline and after treatment. Eight out of 122 ALS outpatients were offered BoTox-A treatment. One declined and the other seven were administered BoTox-A in the lower limbs, every 5-8 months. All of them experienced improvement in the clinical outcome and all but one referred subjective improvement. Moreover, after a median follow-up of 16 months and three injections, BoTox-A effect was maintained with no adverse events. This study provides class IV evidence that BoTox-A is safe , and could be beneficial in the short term and long term in a subset of ALS patients with moderate-to-severe spasticity. PMID- 27383644 TI - Frugal innovation in medicine for low resource settings. AB - Whilst it is clear that technology is crucial to advance healthcare: innovation in medicine is not just about high-tech tools, new procedures or genome discoveries. In constrained environments, healthcare providers often create unexpected solutions to provide adequate healthcare to patients. These inexpensive but effective frugal innovations may be imperfect, but they have the power to ensure that health is within reach of everyone. Frugal innovations are not limited to low-resource settings: ingenuous ideas can be adapted to offer simpler and disruptive alternatives to usual care all around the world, representing the concept of "reverse innovation". In this article, we discuss the different types of frugal innovations, illustrated with examples from the literature, and argue for the need to give voice to this neglected type of innovation in medicine. PMID- 27383645 TI - Diet Shapes Mortality Response to Trauma in Old Tephritid Fruit Flies. AB - Despite the importance of trauma in healthspan and lifespan in humans as well as in non-human species, with one important exception the literature in both gerontology and ecology contains virtually no experimental demographic studies concerned with trauma in any species. We used dietary manipulation [full diet (F) versus sugar-only (S)] to produce four levels of frailty in 55-day old tephritid fruit flies (Anastrepha ludens) that were then subject to the trauma of cage transfer stress (n = 900/sex in each of the 4 treatments). The key results included the following: (1) there is a trauma effect caused by the transfer that depends on previous diet before transfer, new diet after transfer and gender of the fly; (2) males are more vulnerable than females; (3) if initial diet was F, flies are relatively immune against the trauma, and the subsequent diet (F or S) does not matter; (4) however if initial diet was S, then the effect of the trauma depends largely on the diet after the transfer; (5) flies transferred from S to F diets do very well in terms of remaining longevity (i.e. greatest remaining longevity), while flies transferred from S to S diet do poorly (i.e. shortest remaining longevity). We discuss both the strengths and weaknesses of this study and implications of the results. PMID- 27383646 TI - HIF-1alpha Activation Attenuates IL-6 and TNF-alpha Pathways in Hippocampus of Rats Following Transient Global Ischemia. AB - BACKGROUND/AIMS: This study was to examine the role played by hypoxia inducible factor-1 (HIF-1alpha) in regulating pro-inflammatory cytokines (PICs) pathway in the rat hippocampus after cardiac arrest (CA) induced-transient global ischemia followed by cardiopulmonary resuscitation (CPR). Those PICs include interleukin 1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF alpha). METHODS: A rat model of CA induced by asphyxia was used in the current study. Following CPR, the hippocampus CA1 region was obtained for ELISA to determine the levels of HIF-1alpha and PICs; and Western Blot analysis to determine the protein levels of PIC receptors. RESULTS: Our data show that IL 1beta, IL-6 and TNF-alpha were significant elevated in the hippocampus after CPR as compared with control group. This was companied with increasing of HIF-1alpha and the time courses for HIF-1alpha and PICs were similar. In addition, PIC receptors, namely IL-1R, IL-6R and TNFR1 were upregulated in CA rats. Also, stimulation of HIF-1alpha by systemic administration of ML228, HIF-1alpha activator, significantly attenuated the amplified IL-6/IL-6R and TNF-alpha /TNFR1 pathway in the hippocampus of CA rats, but did not modify IL-1beta and its receptor. Moreover, ML228 attenuated upregulated expression of Caspase-3 indicating cell apoptosis evoked by CA. CONCLUSION: Transient global ischemia induced by CA increases the levels of IL-1beta, IL-6 and TNF-alpha and thereby leads to enhancement in their respective receptor in the rat hippocampus. Stabilization of HIF-1alpha plays a role in attenuating amplified expression IL 6R, TNFR1 and Caspase-3 in the processing of transient global ischemia. Results of our study suggest that PICs contribute to cerebral injuries evoked by transient global ischemia and in this pathophysiological process activation of HIF-1alpha improves tissues against ischemic injuries. Our data revealed specific signaling pathways in alleviating CA-evoked global cerebral ischemia by elucidating that HIF-1alpha plays an important role in regulating PIC signal pathways and Caspase-3. The subsequent induction of HIF-1alpha and its target signals is likely a part of the intrinsic neuroprotective effects aimed at attenuating damage as a result of global cerebral ischemia. Thus, targeting one or more of these signaling molecules has clinical implications for treatment and improvement of CA-evoked global cerebral ischemia often observed in clinics. PMID- 27383647 TI - Benefit of Preoperative Oral Steroids during Sinus Surgery when Utilizing Concentrated Topical Epinephrine. AB - BACKGROUND/AIMS: Oral steroids have been advocated in the preoperative setting as a means of reducing intraoperative blood loss and surgical time during sinus surgery. The purpose of this study was to analyze the impact of preoperative oral steroid administration on intraoperative bleeding and surgical duration when coupled with concentrated topical epinephrine. METHODS: The medical records of 302 patients who underwent bilateral 'full house' sinus surgery were reviewed. Concentrated topical epinephrine and inhalational anesthesia was used in all patients. Surgical duration and estimated blood loss were compared between the preoperative steroid-exposed and steroid-naive groups. chi2 and Student's t tests were used for statistical analysis. RESULTS: One hundred and forty-two patients were exposed to steroid, while the remaining 160 were steroid naive. No significant differences were found with respect to surgical time between the steroid-exposed (96.91 +/- 25.97 min) and steroid-naive patients (91.24 +/- 32.29 min, p = 0.100). The steroid-exposed group demonstrated a marginally increased blood loss (66.03 +/- 55.81 ml) as compared to steroid-naive patients (55.00 +/- 38.71 ml, p = 0.048). CONCLUSION: When coupled with intraoperative concentrated topical epinephrine use, preoperative oral steroid administration provides no clinically significant benefit with respect to reduced intraoperative bleeding or surgical duration. PMID- 27383648 TI - Reverse Transcription of Threose Nucleic Acid by a Naturally Occurring DNA Polymerase. AB - Recent advances in polymerase engineering have enabled the replication of xenonucleic acid (XNA) polymers with backbone structures distinct from those found in nature. By introducing a selective amplification step into the replication cycle, functional XNA molecules have been isolated by in vitro selection with binding and catalytic activity. Despite these successes, coding and decoding genetic information in XNA polymers remains limited by the fidelity and catalytic efficiency of engineered XNA polymerases. In particular, the process of reverse transcribing XNA back into DNA for amplification by PCR has been problematic. Here, we show that Geobacillus stearothermophilus (Bst) DNA polymerase I functions as an efficient and faithful threose nucleic acid (TNA) dependent DNA polymerase. Bst DNA polymerase generates ~twofold more cDNA with threefold fewer mutations than Superscript II (SSII), which was previously the best TNA reverse transcriptase. Notably, Bst also functions under standard magnesium-dependent conditions, whereas SSII requires manganese ions to relax the enzyme's substrate specificity. We further demonstrate that Bst DNA polymerase can support the in vitro selection of TNA aptamers by evolving a TNA aptamer to human alpha-thrombin. PMID- 27383649 TI - Absorption of salicylate powders versus tablets following overdose: a poison center observational study. AB - BACKGROUND: Salicylate absorption following overdose of aspirin (ASA) tablet formulations can be prolonged for greater than 24 h. Accordingly, serial serum concentrations are typically recommended to guide treatment. However, there are little published data on absorption following ingestion of powder ASA formulations, and it is not known if delayed ASA absorption occurs following overdose of powder formulations. The objective of this study is to compare the absorption characteristics of powder and tablet formulations of ASA in patients reported to a single poison center. METHODS: Electronic records from an accredited poison center were searched for single substance acute or acute on chronic ingestions of ASA in powder form between 1 January 2002 and 31 January 2014. An identical search for ingestions of ASA tablet products between 1 January 2012 and 31 December 2013 was undertaken as the comparator group. Other inclusion criteria were age >12 years, documented time of ingestion, treatment in a health care facility within nine hours of ingestion and at least two detectable serum salicylate concentrations. RESULTS: 16 of 25 powder and 22 of 49 tablet cases met inclusion criteria for analysis. Repeat serum salicylate concentrations following ingestion of tablets increased or insignificantly changed in 11 of 22 (50%) cases, and median serum salicylate concentrations in followed cases remained elevated for up to 12 h in some cases. In comparison, serum salicylate concentrations following powder ingestions declined in 15 of 16 (94%) cases. One patient, who ingested a powder product, underwent hemodialysis pursuant to an initial serum salicylate concentration of 96 mg/dL. CONCLUSIONS: In contrast to persistent concentrations following overdose of tablets, the majority of serum salicylate concentrations declined following ingestion of powder formulations. In this small study population, these findings suggest that prolonged absorption is unlikely following ingestions of ASA powders. PMID- 27383650 TI - Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation. AB - Amyloid precursor protein (APP) and its cleavage product amyloid beta (Abeta) have been thoroughly studied in Alzheimer's disease. However, APP also appears to be important for neuronal development. Differentiation of induced pluripotent stem cells (iPSCs) towards cortical neurons enables in vitro mechanistic studies on human neuronal development. Here, we investigated expression and proteolytic processing of APP during differentiation of human iPSCs towards cortical neurons over a 100-day period. APP expression remained stable during neuronal differentiation, whereas APP processing changed. alpha-Cleaved soluble APP (sAPPalpha) was secreted early during differentiation, from neuronal progenitors, while beta-cleaved soluble APP (sAPPbeta) was first secreted after deep-layer neurons had formed. Short Abeta peptides, including Abeta1-15/16, peaked during the progenitor stage, while processing shifted towards longer peptides, such as Abeta1-40/42, when post-mitotic neurons appeared. This indicates that APP processing is regulated throughout differentiation of cortical neurons and that amyloidogenic APP processing, as reflected by Abeta1-40/42, is associated with mature neuronal phenotypes. PMID- 27383652 TI - Water Exposure on the Hands in Adolescents: A Report from the BAMSE Cohort. AB - Water exposure on the skin of the hands has previously been studied in adults. The aim of this study was to investigate self-reported water exposure in adolescents in the BAMSE cohort in Stockholm, Sweden. A questionnaire including a question on daily water exposure on the hands was answered by 3,091 adolescents at age 16 years. Exposure < 10 times/day was reported by 28.7% and < 20 times/day by 3.1%; boys had somewhat higher exposure than girls (p = 0.03). In a multivariate analysis, adolescents with dry skin reported higher exposure (adjusted odds ratio (ORadj) 1.4; 95% CI 1.2-1.7), while no statistically significant exposure differences were found in relation to hand eczema or atopic dermatitis. Reported exposure may be considered as baseline exposure during a period of life with limited occupational and domestic duties. PMID- 27383651 TI - Ru(II)/clotrimazole/diphenylphosphine/bipyridine complexes: Interaction with DNA, BSA and biological potential against tumor cell lines and Mycobacterium tuberculosis. AB - Three ruthenium complexes [RuCl(CTZ)(bipy)(P-P)]PF6 [P-P=1,2 bis(diphenylphosphino)ethane (dppe-1), 1,4-bis(diphenylphosphino)butane (dppb-2) and 1,1'-bis(diphenylphosphino)ferrocene (dppf-3), bipy=2,2'-bipiridine and clotrimazole (CTZ) 1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole] were synthesized. These complexes were characterized by a combination of elemental analysis, molar conductivity, infrared and UV-vis spectroscopy, 1H, 13C{1H} and 31P{1H} nuclear magnetic resonance techniques, cyclic voltammetry and mass spectroscopy. Bovine serum albumin binding constants, which were in the range of 1.30-36.00*104M-1, and thermodynamic parameters suggest spontaneous interactions with this protein by electrostatic forces due to the positive charge of the complexes. DNA interactions studied by spectroscopic titration, viscosity measurements, gel electrophoresis, circular dichroism, ethidium bromide displacement and reactions with guanosine and guanosine monophosphate indicated the DNA binding affinity primarily through non-covalent interactions. All complexes 1-3 were tested against the human carcinoma cell lines MCF-7 (breast), A549 (lung) and DU-145 (prostate) presenting promising IC50 values, between 0.50 and 14.00MUM, in some cases lower than the IC50 for the reference drug (cisplatin). The antimicrobial activity assays of the complexes provided evidence that they are potential agents against mycobacterial infections, specifically against Mycobacterium tuberculosis H37Rv. PMID- 27383653 TI - Comparison of the landmark and ultrasound methods in cesarean sections performed under spinal anesthesia on obese pregnants. AB - Difficulties in the palpation of anatomical landmarks in pregnancy due to obesity may create problems in the regional anaesthesia. Objective of this study was to compare ultrasound examination carried out before the procedure with conventional spinal anaesthesia method with papation of bony landmarks in caesarean sections performed under spinal anaesthesia in obese pregnants. Ninety-seven obese pregnants having pre- and post-pregnancy body mass index > 30 kg/m2 were prospectively examined. Patients were randomised to two groups as landmark group (n = 49) and ultrasound group (n = 48). The needle insertion point was determined at L4-L5 level before the procedure through palpation in the landmark group and with the examination in the ultrasound. The numbers of skin punctures and needle passes, total procedure time (TPT) and spinal block occurrence time (SBOT) were recorded. TPT was significantly longer in the ultrasound than in the landmark group (p < 0.001) (8 +/- 2 and 5 +/- 1; respectively). Whereas SBOT values were similar (p = 0.063). The numbers of skin punctures and needle passes were significantly fewer in the ultrasound than in the landmark group (p < 0.001). We believe that, accurate determination of the needle introducing site before the procedure by viewing the vertebral structures through ultrasound examination in obese pregnants could increase the success rate. PMID- 27383654 TI - Outcome of self-expandable metallic stent deployment in patients with malignant gastroduodenal outlet obstruction and Niti-S and WallFlex comparison: a multicenter retrospective clinical study. AB - OBJECTIVES: Several studies report on the outcomes of self-expandable metallic stents (SEMSs) deployment for malignant gastric outlet obstruction (GOO). However, data was mostly based on the analysis of single-center studies including only a small number of patients. This study aimed to evaluate clinical outcomes after the deployment of SEMS in patients with malignant GOO and to compare the clinical outcomes of two metallic stents with different designs. METHODS: Altogether 125 consecutive patients from five institutions were included. Clinical outcomes were evaluated according to technical success, clinical success, stent patency period, survival period and complications. A comparison of clinical outcomes between Niti-S pyloric/duodenal and WallFlex duodenal stents was also undertaken. RESULTS: Rates for clinical and technical success were 100% and 92.0%, respectively. The median stent patency and survival periods were 72.0 days (range 3-775 days) and 75.0 days (range 3-775 days), respectively. The rate of overall adverse events was 28.8%. The rate of stent dysfunction was 16.8%, and that of adverse events, except stent dysfunction was 12.0%. Massive bleeding occurred in two patients as a late complication. The clinical success rate for Niti-S stent was significantly higher than that for WallFlex stent (96.2% vs 84.8%, P = 0.023). CONCLUSIONS: We successfully deployed a SEMS in malignant GOO. The selection of a SEMS with a lower axial force may be important for patients to resume the oral food intake. Additionally, consideration must be given to the appropriate management of fatal bleeding as a late complication. PMID- 27383655 TI - A commentary on de novo MEIS2 mutation causes syndromic developmental delay with persistent gastro-esophageal reflux. PMID- 27383656 TI - Homozygosity mapping guided next generation sequencing to identify the causative genetic variation in inherited retinal degenerative diseases. AB - Inherited retinal degeneration (IRD) are a group of genetically heterogeneous disease of which retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are the most common and severe type. In our study we had taken three unrelated South Indian consanguineous IRD families. Homozygosity mapping was done using Affymetrix 250K Nsp1 GeneChip in each of LCA, Cone-Rod dystrophy (CRD) and autosomal recessive RP (arRP) families followed by targeted re-sequencing by next generation sequencing (NGS) on Illumina MiSeq. Known candidate genes ranging from 1-8 in numbers within the homozygous blocks were identified by homozygosity mapping and targeted NGS revealed the causative mutations; RDH12 c.832A>C, ABCA4 c.1462G>T, CDHR1c.1384_1392delCTCCTGGACinsG, in the LCA, CRD and arRP families, respectively. The identified mutations were validated by Sanger sequencing, segregation in the families and their absence in 200 control chromosomes. Homozygosity mapping guided targeted NGS, especially when more numbers of known candidate genes within the homozygous blocks are observed is a comprehensive method for mutation identification. Molecular data from a larger retinal degenerative disease cohort would reveal the spectrum and prevalence of mutations and genes in Indian population. Molecular diagnosis also aids in genetic counseling, offering carrier and prenatal testing to family members. PMID- 27383657 TI - SIX2 haploinsufficiency causes conductive hearing loss with ptosis in humans. AB - The ossicles represent one of the most fundamental morphological features in evolutionary biology of the mammalians. The mobile ossicular morphology abnormalities result in the severe conductive hearing loss. Development and patterning of the middle ear malformation depend on genetic and environmental causes. However, the genetic basis for the risk of congenital ossicle malformation is poorly understood. We show here nine affected individuals in a Chinese pedigree who had bilateral conductive hearing loss with ptosis. We performed whole-genome sequencing and array comparative genomic hybridization (CGH) analysis on DNA samples from the Chinese pedigree. We confirmed the presence of a novel 60 kb heterozygous deletion in size, encompassing SIX2 in our family. Mutation screening in 169 sporadic cases with external ear and middle ear malformations identified no pathogenic variant or polymorphism. We suggest SIX2 haploinsufficiency as a potential congenital factor could be attributed to developmental malformation of the middle ear ossicles and upper eyelid. To the best of our knowledge, this is the first report to provide a description of copy number variation in the SIX2 gene resulting in syndromic conductive hearing loss. PMID- 27383659 TI - Occupational exposure to nitrous oxide during procedural pain control in children: a comparison of different inhalation techniques and scavenging systems. AB - BACKGROUND: Nitrous oxide (N2 O 50% in oxygen) is commonly used for painful procedures in children. Potential negative health effects associated with chronic workplace exposure limit its use. Safe occupational N2 O exposure concentrations are below 25 ppm environmental concentration as a time-weighted average (TWA) and below 200 ppm as a short-time exposure level (STEL) of 15 min. AIM: The aim was to assess occupational exposure of staff during nitrous oxide administration to children using different inhalation delivery devices and scavenging systems. METHODS: Staff nitrous oxide exposure during use of a double face mask (DFM) with or without a demand valve (DV) was compared with a conventional single face mask (FM). We also compared exposure using the hospital central scavenging system with a portable evacuation system. N2 O concentrations, representing exposure values, were monitored within proximity to staff. Urine N2 O concentration was measured in staff administering the N2 O at the end of the procedural session. RESULTS: The mean and median values of TWA and STEL within the working area were lower than recommended values in the DFM (10.8, 11.6 ppm for TWA; 13.9, 11.0 ppm for STEL) and DFM-DV groups (2.3, 2.8 ppm for TWA; 4.4, 3.5 ppm for STEL) using the portable evacuation system. The N2 O urine exposure in DFM-DV group was lower than DFM group: a mean difference of 9.56 ppm (95% CI 2.65-16.46). Staff N2 O urinary concentrations were within safe biological limits in both the DFM and DFM DV groups. High exposure concentrations to N2 O were recorded in all FM and FM-DV environmental and biological samples. CONCLUSIONS: The DFM system, with or without a DV, connected to a portable evacuation system during N2 O administration to children for painful procedures kept N2 O levels within the local environment below recommended limits. PMID- 27383660 TI - Electron transfer mechanism of catalytic superoxide dismutation via Cu(ii/i) complexes: evidence of cupric-superoxo/-hydroperoxo species. AB - To understand the electron transfer mechanisms (outer versus inner sphere) of catalytic superoxide dismutation via a Cu(ii/i) redox couple such as occur in the enzyme copper-zinc superoxide dismutase, the Cu(ii/i) complexes [(L1)2Cu](ClO4)2.CH3CN, (1.CH3CN) and [(L1)2Cu](ClO4), (2) supported by a bis N2Sthioether ligand, 2-pyridyl-N-(2'-methylthiophenyl)methyleneimine (L1) have been synthesized and structurally characterised. Both 1 and 2 display the same cyclic voltammogram (CV) featuring a quasireversible response at E1/2 = +0.33 V vs. SCE that falls in the SOD potential window of -0.04 V to +0.99 V. These complexes catalytically dismutate superoxide radicals at 298 K in aqueous medium (the IC50 for 1 is 2.15 MUM). Electronic absorption spectra (233 K and 298 K), FTIR, ESI mass spectra, CV (233 K and 298 K) and DFT calculations collectively indicate formation of [(L1)2Cu(O2(-))](+), [(L1)2Cu(O2(2-))] and [(L1)2Cu(OOH( ))](+) species and help to elucidate the electron transfer mechanism for the SOD function of 1 and 2. Once O2(-) binds to Cu(II) (evident at 233 K), the first step of the catalytic cycle (Cu(II) + O2(-)-> Cu(I) + O2) does not follow but the second step (Cu(I) + O2(-) + 2H(+)-> H2O2 + Cu(II)) does follow. Therefore, the catalytic disproportionation of superoxide radicals via1 and 2 at 298 K indicates that the first and second steps of the catalytic cycle proceed through outer and inner sphere electron transfer mechanisms, respectively. Feasibility of the first step to occur in pure aprotic solvent (where 18-crown-6-ether is used to solubilise KO2) was tested and also supports the same notion of the electron transfer mechanisms as stated above. PMID- 27383658 TI - MicroRNAs in extracellular vesicles: potential cancer biomarkers. AB - Extracellular vesicles (EV) are small membrane-bound structures that are secreted by various cell types, including tumor cells. Recent studies have shown that EVs are important for cell-to-cell communication, locally and distantly; horizontally transferring DNA, mRNA, microRNA (miRNA), proteins and lipids. In the context of cancer biology, tumor-derived EVs are capable of modifying the microenvironment, promoting tumor progression, immune evasion, angiogenesis and metastasis. miRNAs contained within EVs are functionally associated with cancer progression, metastasis and aggressive tumor phenotypes. These factors, along with their stability in bodily fluids, have led to extensive investigations on the potential role of circulating EV-derived miRNAs as tumor biomarkers. In this review, we summarize the current understanding of circulating EV miRNAs in human cancer, and discuss their clinical utility and challenges in functioning as biomarkers. PMID- 27383662 TI - Temporal patterns of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography sinonasal uptake after treatment of sinonasal malignancy. AB - BACKGROUND: Current guidelines have identified 10 to 12 weeks posttreatment as the ideal time-point for improved diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) for deep tissue sites of the head and neck. After treatment, the sinonasal skull base is predisposed to prolonged inflammation that may render this time-point inappropriate for initial posttreatment imaging surveillance for sinonasal malignancies. The purpose of this study is to evaluate temporal trends in 18 F-fluorodeoxyglucose (18 FDG) sinonasal uptake after treatment for sinonasal malignancies to better elucidate the optimal time-point for initial PET/CT posttreatment evaluation in this patient population. METHODS: A retrospective analysis of all successfully treated and non-locally recurrent sinonasal malignancies over a 15-year study period (2000 to 2015) was performed at our institution. Posttreatment 18 FDG PET/CT standardized uptake value data were collected and compared between various time points (2 to 4 months, 5 to 12 months, 5 to 24 months, and 13 to 24 months) using an independent-samples t test. RESULTS: A statistically significant difference was noted between the posttreatment time windows 2 to 4 and 5 to 12 months (p = 0.048) as well as 2 to 4 and 5 to 24 months (p = 0.02). A trend toward significance was seen when comparing 2 to 4 and 13 to 24 months (p = 0.083). CONCLUSION: Our analysis of PET/CT in patients previously treated for sinonasal malignancy suggests that the posttreatment sinonasal skull base is characterized by a prolonged period of hypermetabolism that endures beyond the period previously described for deep tissue sites of the head and neck. These findings prompt a reevaluation of the previously described 10- to 12-week cutoff point for initial posttreatment PET/CT for head and neck squamous cell carcinoma as applied to sinonasal malignancies. PMID- 27383663 TI - Phenotypic flexibility of gape anatomy fine-tunes the aquatic prey-capture system of newts. AB - A unique example of phenotypic flexibility of the oral apparatus is present in newts (Salamandridae) that seasonally change between an aquatic and a terrestrial habitat. Newts grow flaps of skin between their upper and lower jaws, the labial lobes, to partly close the corners of the mouth when they adopt an aquatic lifestyle during their breeding season. Using hydrodynamic simulations based on MUCT-scans and cranial kinematics during prey-capture in the smooth newt (Lissotriton vulgaris), we showed that this phenotypic flexibility is an adaptive solution to improve aquatic feeding performance: both suction distance and suction force increase by approximately 15% due to the labial lobes. As the subsequent freeing of the corners of the mouth by resorption of the labial lobes is assumed beneficial for the terrestrial capture of prey by the tongue, this flexibility of the mouth fine-tunes the process of capturing prey throughout the seasonal switching between water and land. PMID- 27383664 TI - A systematic analysis and comparison of warfarin initiation strategies. AB - OBJECTIVE: Randomized trials have reported inconsistent evidence on the effectiveness of algorithms that use genotypes to initiate warfarin therapy. The Clarification of Optimal Anticoagulation through Genetics (COAG) trial initiated therapy on the basis of predicted maintenance doses, with a pharmacogenetic guided algorithm in one study group and a clinically guided algorithm in the other. The European Pharmacogenetics of Anticoagulant Therapy (EU-PACT) consortium initiated therapy on the basis of loading doses, with an algorithm based prediction in one study group and a fixed-dose regimen in the other. To understand the differences between these trials, we compared the initial doses between alternative dosing algorithms (the pharmacogenetic-guided and clinically guided algorithms developed by Gage and colleagues and those developed by the International Warfarin Pharmacogenetics Consortium) and between the COAG and EU PACT dose-initiation strategies. METHODS: This was a secondary analysis of the COAG trial - a double-blind, randomized-controlled trial (2009-2013) - conducted at 18 clinical centers in the USA, which included 1010 adults initiating warfarin therapy, of whom 719 achieved maintenance dose. RESULTS: Among COAG participants, the distribution of initial doses differed between algorithms, but showed similar prediction accuracy for maintenance dose. However, had the COAG trial implemented the EU-PACT strategy, the 3-day initial dose would have been 4.8 mg greater among participants randomized to pharmacogenetic-guided dosing, but only 2.5 mg greater among participants randomized to clinically guided dosing (P<0.001). CONCLUSION: Compared with the COAG trial, the EU-PACT trial used systematically larger loading doses in the pharmacogenetic-guided group and might have inadequately adjusted for clinical variability in warfarin dose requirements in the fixed-dose group. PMID- 27383666 TI - Functionalized Nanocellulose-Integrated Heterolayered Nanomats toward Smart Battery Separators. AB - Alternative materials obtained from natural resources have recently garnered considerable attention as an innovative solution to bring unprecedented advances in various energy storage systems. Here, we present a new class of heterolayered nanomat-based hierarchical/asymmetric porous membrane with synergistically coupled chemical activity as a nanocellulose-mediated green material strategy to develop smart battery separator membranes far beyond their current state-of-the art counterparts. This membrane consists of a terpyridine (TPY)-functionalized cellulose nanofibril (CNF) nanoporous thin mat as the top layer and an electrospun polyvinylpyrrolidone (PVP)/polyacrylonitrile (PAN) macroporous thick mat as the support layer. The hierarchical/asymmetric porous structure of the heterolayered nanomat is rationally designed with consideration of the trade-off between leakage current and ion transport rate. The TPY (to chelate Mn(2+) ions) and PVP (to capture hydrofluoric acid)-mediated chemical functionalities bring a synergistic coupling in suppressing Mn(2+)-induced adverse effects, eventually enabling a substantial improvement in the high-temperature cycling performance of cells. PMID- 27383665 TI - Serum Testosterone Concentrations and Urinary Bisphenol A, Benzophenone-3, Triclosan, and Paraben Levels in Male and Female Children and Adolescents: NHANES 2011-2012. AB - BACKGROUND: Exposure to environmental phenols (e.g., bisphenol A, benzophenone-3, and triclosan) and parabens is widespread in the population. Many of these chemicals have been shown to have anti-androgenic effects both in vitro and in vivo. OBJECTIVE: We examined the association of bisphenol A (BPA), benzophenone-3 (BP-3), triclosan (TCS), and parabens with serum total testosterone (TT) levels in child and adolescent participants (ages 6-19 years) in the National Health and Nutrition Examination Survey (NHANES) 2011-2012. METHODS: We performed multivariable linear regression to estimate associations between natural log transformed serum TT and quartiles of urinary BPA, BP-3, TCS, and parabens in male and female children (ages 6-11 years) and adolescents (ages 12-19 years). RESULTS: BP-3 and BPA were associated with significantly lower TT in male adolescents, and BPA was associated with significantly higher TT in female adolescents. TT was not consistently associated with TCS or total parabens in children or adolescents of either sex. CONCLUSIONS: To our knowledge, this is the first study to report an association of both BP-3 and BPA with serum TT in adolescents. Associations between BPA and TT differed according to sex in adolescents, with inverse associations in boys and positive associations in girls. BP-3 was associated with significantly lower TT in adolescent boys only. However, because of the limitations inherent to the cross-sectional study design, further studies are needed to confirm and elucidate on our findings. Citation: Scinicariello F, Buser MC. 2016. Serum testosterone concentrations and urinary bisphenol A, benzophenone-3, triclosan, and paraben levels in male and female children and adolescents: NHANES 2011-2012. Environ Health Perspect 124:1898 1904; http://dx.doi.org/10.1289/EHP150. PMID- 27383680 TI - Conversion of Dinitrogen to Ammonia by FeN3-Embedded Graphene. AB - Nitrogen fixation is one of the most important issues but a long-standing challenge in chemistry. Here, we propose FeN3-embedded graphene as the catalyst for nitrogen fixation from first-principles calculations. Results show that in view of the chemical coordination, the FeN3 center is highly spin-polarized with a localized magnetic moment substantially to promote N2 adsorption and activate its inert N-N triple bond. The synergy between the graphene and FeN3 equips the system with novel features for the catalytic conversion of the activated N2 into NH3 via a six-proton and six-electron process, following three possible reaction pathways at room temperature. Our findings provide a rational paradigm for catalytic nitrogen fixation that would be conducive to ammonia production. PMID- 27383681 TI - Isolation of Inositol Hexaphosphate (IHP)-Degrading Bacteria from Arbuscular Mycorrhizal Fungal Hyphal Compartments Using a Modified Baiting Method Involving Alginate Beads Containing IHP. AB - Phytate (inositol hexaphosphate; IHP)-degrading microbes have been suggested to contribute to arbuscular mycorrhizal fungi (AMF)-mediated P transfer from IHP to plants; however, no IHP degrader involved in AMF-mediated P transfer has been isolated to date. We herein report the isolation of IHP-degrading bacteria using a modified baiting method. We applied alginate beads as carriers of IHP powder, and used them as recoverable IHP in the AM fungal compartment of plant cultivation experiments. P transfer from IHP in alginate beads via AMF was confirmed, and extracted DNA from alginate beads was analyzed by denaturing gradient gel electrophoresis targeting the 16S rRNA gene and a clone library method for the beta-propeller phytase (BPP) gene. The diversities of the 16S rRNA and BPP genes of microbes growing on IHP beads were simple and those of Sphingomonas spp. and Caulobacter spp. dominated. A total of 187 IHP-utilizing bacteria were isolated and identified, and they were consistent with the results of DNA analysis. Furthermore, some isolated Sphingomonas spp. and Caulobacter sp. showed IHP-degrading activity. Therefore, we successfully isolated dominant IHP degrading bacteria from IHP in an AMF hyphal compartment. These strains may contribute to P transfer from IHP via AMF. PMID- 27383683 TI - Growth Rate of and Gene Expression in Bradyrhizobium diazoefficiens USDA110 due to a Mutation in blr7984, a TetR Family Transcriptional Regulator Gene. AB - Previous transcriptome analyses have suggested that a gene cluster including a transcriptional regulator (blr7984) of the tetracycline repressor family was markedly down-regulated in symbiosis. Since blr7984 is annotated to be the transcriptional repressor, we hypothesized that it is involved in the repression of genes in the genomic cluster including blr7984 in symbiotic bacteroids. In order to examine the function and involvement of the blr7984 gene in differentiation into bacteroids, we compared the free-living growth/symbiotic phenotype and gene expression between a blr7984-knockout mutant and the wild-type strain of Bradyrhizobium diazoefficiens USDA110. The mutant transiently increased the cell growth rate under free-living conditions and nodule numbers over those with the wild-type strain USDA110. The expression of three genes adjacent to the disrupted blr7984 gene was strongly up-regulated in the mutant in free-living and symbiotic cells. The mutant also induced the expression of genes for glutathione S-transferase, cytochrome c oxidases, ABC transporters, PTS sugar transport systems, and flagella synthesis under free-living conditions. bll7983 encoding glutathione S-transferase was up-regulated the most by the blr7984 disruption. Since redox regulation by glutathione is known to be involved in cell division in prokaryotes and eukaryotes, the strong expression of glutathione S-transferase encoded by the bll7983 gene may have caused redox changes in mutant cells, which resulted in higher rates of cell division. PMID- 27383684 TI - Analyzing infant head flatness and asymmetry using kernel density estimation of directional surface data from a craniofacial 3D model. AB - Infant skull deformation is analyzed using the distribution of head normal vector directions computed from a 3D image. Severity of flatness and asymmetry are quantified by functionals of the kernel estimate of the normal vector direction density. Using image data from 99 infants and clinical deformation ratings made by experts, our approach is compared with some recently suggested methods. The results show that the proposed method performs competitively. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27383685 TI - In vitro storage of unfertilized eggs of the Eurasian perch and its effect on egg viability rates and the occurrence of larval malformations. AB - Ova ageing is the most important factor affecting fish egg quality after ovulation. Long-term storage of fish ova, using cryopreservation and vitrification techniques, has been unsuccessful to date. Instead, short-term in vitro ova storage has been used successfully and optimized in some cultured fish species. In vitro ova storage can drastically improve mass production of larvae and juveniles in the hatcheries by providing the possibility of the synchronous artificial fertilization for different females. To study how long unfertilized eggs of Eurasian perch (Perca fluviatilis L.) can retain their fertilizing ability after stripping, eggs were stored at temperatures of 4 degrees C, 8 degrees C and 12 degrees C for 72 h post-stripping (HPS). The stored eggs of four female perch were separately fertilized at 0 h (i.e. control eggs fertilized before storage) and at 6-hour intervals during the experimental period of 72 h. The embryos reaching the eyed-egg and hatched-larvae stages, eyed-egg mortality and larval malformation rates were recorded as indices of egg quality. The results indicated that the maximum eyed eggs and hatched larvae (86% and 63%, respectively) were observed for eggs fertilized immediately after stripping, whereas the storage of the eggs at 4 degrees C for 48 HPS decreased the eyed-egg and hatched-larvae rates to 46% and 17%, respectively. The use of a higher storage temperature resulted in a more rapid decrease in egg viability: eyed-egg and hatched-larvae rates of 23% and 9%, respectively, were obtained after 48 HPS storage at 8 degrees C and 2% and 1% for eggs stored at 12 degrees C. Eyed-egg mortality and larval malformation rates were not significantly affected by post stripping ova ageing for at least up to 36 h. Thereafter, both values increased significantly and were measured to be the highest in the most aged ova. The present study demonstrated that stripped Eurasian perch eggs can be stored for at least 12 h at 4 degrees C to 12 degrees C without a significant reduction in their quality. PMID- 27383682 TI - Metagenomics and Bioinformatics in Microbial Ecology: Current Status and Beyond. AB - Metagenomic approaches are now commonly used in microbial ecology to study microbial communities in more detail, including many strains that cannot be cultivated in the laboratory. Bioinformatic analyses make it possible to mine huge metagenomic datasets and discover general patterns that govern microbial ecosystems. However, the findings of typical metagenomic and bioinformatic analyses still do not completely describe the ecology and evolution of microbes in their environments. Most analyses still depend on straightforward sequence similarity searches against reference databases. We herein review the current state of metagenomics and bioinformatics in microbial ecology and discuss future directions for the field. New techniques will allow us to go beyond routine analyses and broaden our knowledge of microbial ecosystems. We need to enrich reference databases, promote platforms that enable meta- or comprehensive analyses of diverse metagenomic datasets, devise methods that utilize long-read sequence information, and develop more powerful bioinformatic methods to analyze data from diverse perspectives. PMID- 27383686 TI - Synaptic plasticity: Feast or famine. PMID- 27383687 TI - Gut-brain communication: Making friends with microbes. PMID- 27383688 TI - Neurodevelopmental disorders: Touching on the issue. PMID- 27383689 TI - How much do universal anthropometric standards bias the global monitoring of obesity and undernutrition? AB - Each year, hundreds of articles in population health and nutrition, many in high profile journals, use standard cutoffs based on weight and height as assessments of obesity and undernutrition. These global efforts to monitor overweight and underweight often rest on the assumption that ethnic differences in underlying body form are sufficiently small to permit universal anthropometric cutoffs for comparing excess and insufficient body fat across populations. However, a century of work in human biological variation suggests that human populations can vary dramatically in underlying body form in a way that may require population sensitive cutoffs for monitoring. Here, we describe recently developed methods that can provide population-sensitive assessments of both excess and insufficient energy reserves in a wide range of countries. We use this approach to illustrate how worldwide variation in human body form is far more widespread than previously thought, and that it can occur at several geographic scales, including the level of world regions, countries and populations within countries. The findings also suggest that using standard cutoffs that ignore this variation can underestimate current obesity levels in adults by more than 400-500 million while also incorrectly prioritizing high-risk areas for undernutrition in children in key regions around the world. PMID- 27383690 TI - Abnormal Uterine Bleeding: American College of Nurse-Midwives. AB - Variations in uterine bleeding, termed abnormal uterine bleeding, occur commonly among women and often are physiologic in nature with no significant consequences. However, abnormal uterine bleeding can cause significant distress to women or may signify an underlying pathologic condition. Most women experience variations in menstrual and perimenstrual bleeding in their lifetimes; therefore, the ability of the midwife to differentiate between normal and abnormal bleeding is a key diagnostic skill. A comprehensive history and use of the PALM-COEIN classification system will provide clear guidelines for clinical management, evidence-based treatment, and an individualized plan of care. The purpose of this Clinical Bulletin is to define and describe classifications of abnormal uterine bleeding, review updated terminology, and identify methods of assessment and treatment using a woman-centered approach. PMID- 27383692 TI - Being in togetherness: meanings of encounters within primary healtcare setting for patients living with long-term illness. AB - AIMS AND OBJECTIVES: The aim of this study was to elucidate meanings of encounters for patients with long-term illness within the primary healthcare setting. BACKGROUND: Good encounters can be crucial for patients in terms of how they view their quality of care. Therefore, it is important to understand meanings of interactions between patients and healthcare personnel. DESIGN: A phenomenological hermeneutic method was used to analyse the interviews. METHODS: Narrative interviews with ten patients with long-term illness were performed, with a focus on their encounters with healthcare personnel within the primary healthcare setting. A phenomenological hermeneutical approach was used to interpret the interview texts. RESULTS: The results demonstrated that patients felt well when they were seen as an important person and felt welcomed by healthcare personnel. Information and follow-ups regarding the need for care were essential. Continuity with the healthcare personnel was one way to establish a relationship, which contributed to patients' feelings of being seen and understood. Good encounters were important for patients' feelings of health and well-being. Being met with mistrust, ignorance and nonchalance had negative effects on patients' perceived health and well-being and led to feelings of lower confidence regarding the care received. CONCLUSIONS: Patients described a great need to be confirmed and met with respect by healthcare personnel, which contributed to their sense of togetherness. Having a sense of togetherness strengthened patient well-being. RELEVANCE TO CLINICAL PRACTICE: By listening and responding to patients' needs and engaging in meetings with patients in a respectful manner, healthcare personnel can empower patients' feelings of health and well-being. Healthcare personnel need to be aware of the significance of these actions because they can make patients experience feelings of togetherness, even if patients meet with different care personnel at each visit. PMID- 27383691 TI - Alien Mindscapes-A Perspective on the Search for Extraterrestrial Intelligence. AB - Advances in planetary and space sciences, astrobiology, and life and cognitive sciences, combined with developments in communication theory, bioneural computing, machine learning, and big data analysis, create new opportunities to explore the probabilistic nature of alien life. Brought together in a multidisciplinary approach, they have the potential to support an integrated and expanded Search for Extraterrestrial Intelligence (SETI (1) ), a search that includes looking for life as we do not know it. This approach will augment the odds of detecting a signal by broadening our understanding of the evolutionary and systemic components in the search for extraterrestrial intelligence (ETI), provide more targets for radio and optical SETI, and identify new ways of decoding and coding messages using universal markers. KEY WORDS: SETI Astrobiology-Coevolution of Earth and life-Planetary habitability and biosignatures. Astrobiology 16, 661-676. PMID- 27383693 TI - Trangmolins A-F with an Unprecedented Structural Plasticity of the Rings A and B: New Insight into Limonoid Biosynthesis. AB - The absolute stereostructures of trangmolins A-F (1-6), limonoids with three new and one known topologies of the rings A and B, were unambiguously determined by NMR spectroscopic investigations, single-crystal XRD analysis, and quantum chemical electronic circular dichroism calculations. Compounds 1-3 contain a hexahydro-1H-inden-4-one motif, compound 4 comprises a hexahydro-2,6 methanobenzofuran-7-one cage, and compound 5 consists of a hexahydro-2H-2,8 epoxychromene scaffold. The C1-C30 linkage in 1-3 and the C3-C30 connection in 4 form two unprecedented types of ring A/B-fused carbobicyclic cores: viii and ix. The oxidative cleavage of the C2-C3 bond in 5 and heterocyclization in 4 and 5 constitute the unprecedented tricyclic 6/6/5 ring A/B(1) /B(2) - and 6/5/6 ring A(1) A(2) /B-fused topologies, respectively, which are uncovered, for the first time, in the construction of limonoid architectures. The diverse cyclization patterns of 1-6 reveal an unparalleled structural plasticity of rings A and B in limonoid biosynthesis. PMID- 27383694 TI - Diagnostic accuracy of laparoscopy following computed tomography (CT) scanning for assessing the resectability with curative intent in pancreatic and periampullary cancer. AB - BACKGROUND: Surgical resection is the only potentially curative treatment for pancreatic and periampullary cancer. A considerable proportion of patients undergo unnecessary laparotomy because of underestimation of the extent of the cancer on computed tomography (CT) scanning. Laparoscopy can detect metastases not visualised on CT scanning, enabling better assessment of the spread of cancer (staging of cancer). This is an update to a previous Cochrane Review published in 2013 evaluating the role of diagnostic laparoscopy in assessing the resectability with curative intent in people with pancreatic and periampullary cancer. OBJECTIVES: To determine the diagnostic accuracy of diagnostic laparoscopy performed as an add-on test to CT scanning in the assessment of curative resectability in pancreatic and periampullary cancer. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, EMBASE via OvidSP (from inception to 15 May 2016), and Science Citation Index Expanded (from 1980 to 15 May 2016). SELECTION CRITERIA: We included diagnostic accuracy studies of diagnostic laparoscopy in people with potentially resectable pancreatic and periampullary cancer on CT scan, where confirmation of liver or peritoneal involvement was by histopathological examination of suspicious (liver or peritoneal) lesions obtained at diagnostic laparoscopy or laparotomy. We accepted any criteria of resectability used in the studies. We included studies irrespective of language, publication status, or study design (prospective or retrospective). We excluded case-control studies. DATA COLLECTION AND ANALYSIS: Two review authors independently performed data extraction and quality assessment using the QUADAS-2 tool. The specificity of diagnostic laparoscopy in all studies was 1 because there were no false positives since laparoscopy and the reference standard are one and the same if histological examination after diagnostic laparoscopy is positive. The sensitivities were therefore meta-analysed using a univariate random-effects logistic regression model. The probability of unresectability in people who had a negative laparoscopy (post-test probability for people with a negative test result) was calculated using the median probability of unresectability (pre-test probability) from the included studies, and the negative likelihood ratio derived from the model (specificity of 1 assumed). The difference between the pre-test and post-test probabilities gave the overall added value of diagnostic laparoscopy compared to the standard practice of CT scan staging alone. MAIN RESULTS: We included 16 studies with a total of 1146 participants in the meta-analysis. Only one study including 52 participants had a low risk of bias and low applicability concern in the patient selection domain. The median pre-test probability of unresectable disease after CT scanning across studies was 41.4% (that is 41 out of 100 participants who had resectable cancer after CT scan were found to have unresectable disease on laparotomy). The summary sensitivity of diagnostic laparoscopy was 64.4% (95% confidence interval (CI) 50.1% to 76.6%). Assuming a pre-test probability of 41.4%, the post-test probability of unresectable disease for participants with a negative test result was 0.20 (95% CI 0.15 to 0.27). This indicates that if a person is said to have resectable disease after diagnostic laparoscopy and CT scan, there is a 20% probability that their cancer will be unresectable compared to a 41% probability for those receiving CT alone.A subgroup analysis of people with pancreatic cancer gave a summary sensitivity of 67.9% (95% CI 41.1% to 86.5%). The post-test probability of unresectable disease after being considered resectable on both CT and diagnostic laparoscopy was 18% compared to 40.0% for those receiving CT alone. AUTHORS' CONCLUSIONS: Diagnostic laparoscopy may decrease the rate of unnecessary laparotomy in people with pancreatic and periampullary cancer found to have resectable disease on CT scan. On average, using diagnostic laparoscopy with biopsy and histopathological confirmation of suspicious lesions prior to laparotomy would avoid 21 unnecessary laparotomies in 100 people in whom resection of cancer with curative intent is planned. PMID- 27383695 TI - Molecular Characterization and Epidemiologic Study of NDM-1-Producing Extensively Drug-Resistant Escherichia coli. AB - The emergence and dissemination of NDM-1 (New Delhi metallo-beta-lactamase-1) producing Enterobacteriaceae have resulted in a worldwide public health risk. This study described a high incidence and endemic spread of NDM-1-producing extensively drug-resistant Escherichia coli in a teaching hospital in Zhejiang province, China. We recovered six nonduplicated NDM-1-producing E. coli isolates from May 2014 to August 2014 with positive modified Hodge test and EDTA synergistic test. These isolates were highly resistant to beta-lactam antimicrobials, aminoglycosides, and quinolones. PCR and DNA sequences analysis showed that all isolates carried the blaNDM-1, blaSHV-11, aac(6')-ib-cr, and qnrB. Several isolates also harbored blaCTX-M-1, blaCTX-M-9, rmtB, and qnrA. Southern blot confirmed that blaNDM-1 was located on the same ~55 kb plasmid and conjugation experiments further proved the contransferable characteristic of blaNDM-1. The ompC sequences showed various mutations, which was related to multidrug resistance in E. coli. Pulsed-field gel electrophoresis identified four of six isolates that belonged to the same genotype. Multilocus sequence typing assigned them to ST2, except one strain that belonged to ST594. Our study demonstrated that the resistance-associated genes and the loss of the outer membrane proteins could account for high resistance of NDM-1-producing E. coli to multiple antimicrobial drugs. Both horizontal transfer of IncN and transmission of ST2 were responsible for the spread of drug resistance. These findings highlighted an urgent need to limit the further dissemination of NDM-1-producing E. coli in this region. PMID- 27383696 TI - Development of spondyloarthropathy following episodes of macrophage activation syndrome in children with heterozygous mutations in haemophagocytic lymphohistiocytosis-associated genes. PMID- 27383697 TI - New impact factor and Editors of the Journal of Applied Oral Science. PMID- 27383698 TI - Effects of cervical mobilization and exercise on pain, movement and function in subjects with temporomandibular disorders: a single group pre-post test. AB - OBJECTIVE: To investigate the effect of a rehabilitation program based on cervical mobilization and exercise on clinical signs and mandibular function in subjects with temporomandibular disorder (TMD). MATERIAL AND METHODS: Single group pre-post test, with baseline comparison. SUBJECTS: Twelve women (22.08+/ 2.23 years) with myofascial pain and mixed TMD according to the Research Diagnostic Criteria for Temporomandibular Disorders. OUTCOME MEASURES: Subjects were evaluated three times: twice before (baseline phase) and once after intervention. Self-reported pain, jaw function [according to the Mandibular Functional Impairment Questionnaire (MFIQ)], pain-free maximum mouth opening (MMO), and pressure pain thresholds (PPTs) of both masseter and temporalis muscles were obtained. Baseline and post-intervention differences were investigated, and effect size was estimated through Cohen's d coefficient. RESULTS: Jaw function improved 7 points on the scale after the intervention (P=0.019), and self-reported pain was significantly reduced (P=0.009). Pain-free MMO varied from 32.3+/-8.8 mm to 38+/-8.8 mm and showed significant improvement (P=0.017) with moderate effect size when compared to the baseline phase. PPT also increased with moderate effect size, and subjects had the baseline values changed from 1.23+/-0.2 kg/cm2 to 1.4+/-0.2 kg/cm2 in the left masseter (P=0.03), from 1.31+/-0.28 kg/cm2 to 1.51+/-0.2 kg/cm2 in the right masseter (P>0.05), from 1.32+/-0.2 kg/cm2 to 1.46+/-0.2 kg/cm2 in the left temporalis (P=0.047), and from 1.4+/-0.2 kg/cm2 to 1.67+/-0.3 kg/cm2 in the right temporalis (P=0.06). CONCLUSIONS: The protocol caused significant changes in pain-free MMO, self reported pain, and functionality of the stomatognathic system in subjects with myofascial TMD, regardless of joint involvement. Even though these differences are statistically significant, their clinical relevance is still questionable. PMID- 27383699 TI - Evaluation of the remineralization capacity of CPP-ACP containing fluoride varnish by different quantitative methods. AB - OBJECTIVE: The aim of this study was to evaluate the efficacy of CPP-ACP containing fluoride varnish for remineralizing white spot lesions (WSLs) with four different quantitative methods. MATERIAL AND METHODS: Four windows (3x3 mm) were created on the enamel surfaces of bovine incisor teeth. A control window was covered with nail varnish, and WSLs were created on the other windows (after demineralization, first week and fourth week) in acidified gel system. The test material (MI Varnish) was applied on the demineralized areas, and the treated enamel samples were stored in artificial saliva. At the fourth week, the enamel surfaces were tested by surface microhardness (SMH), quantitative light-induced fluorescence-digital (QLF-D), energy-dispersive spectroscopy (EDS) and laser fluorescence (LF pen). The data were statistically analyzed (alpha=0.05). RESULTS: While the LF pen measurements showed significant differences at baseline, after demineralization, and after the one-week remineralization period (p<0.05), the difference between the 1- and 4-week was not significant (p>0.05). With regards to the SMH and QLF-D analyses, statistically significant differences were found among all the phases (p<0.05). After the 1- and 4-week treatment periods, the calcium (Ca) and phosphate (P) concentrations and Ca/P ratio were higher compared to those of the demineralization surfaces (p<0.05). CONCLUSION: CPP-ACP containing fluoride varnish provides remineralization of WSLs after a single application and seems suitable for clinical use. PMID- 27383700 TI - Effect of addition of nano-hydroxyapatite on physico-chemical and antibiofilm properties of calcium silicate cements. AB - OBJECTIVE: Mineral Trioxide Aggregate (MTA) is a calcium silicate cement composed of Portland cement (PC) and bismuth oxide. Hydroxyapatite has been incorporated to enhance mechanical and biological properties of dental materials. This study evaluated physicochemical and mechanical properties and antibiofilm activity of MTA and PC associated with zirconium oxide (ZrO2) and hydroxyapatite nanoparticles (HAn). MATERIAL AND METHODS: White MTA (Angelus, Brazil); PC (70%)+ZrO2 (30%); PC (60%)+ZrO2 (30%)+HAn (10%); PC (50%)+ZrO2 (30%)+HAn (20%) were evaluated. The pH was assessed by a digital pH-meter and solubility by mass loss. Setting time was evaluated by using Gilmore needles. Compressive strength was analyzed by mechanical test. Samples were radiographed alongside an aluminum step wedge to evaluate radiopacity. For the antibiofilm evaluation, materials were placed in direct contact with E. faecalis biofilm induced on dentine blocks. The number of colony-forming units (CFU mL-1) in the remaining biolfilm was evaluated. The results were submitted to ANOVA and the Tukey test, with 5% significance. RESULTS: There was no difference in pH levels of PC+ZrO2, PC+ZrO2+HAn (10%) and PC+ZrO2+HAn (20%) (p>0.05) and these cements presented higher pH levels than MTA (p<0.05). The highest solubility was observed in PC+ZrO2+HAn (10%) and PC+ZrO2+HAn (20%) (p<0.05). MTA had the shortest initial setting time (p<0.05). All the materials showed radiopacity higher than 3 mmAl. PC+ZrO2 and MTA had the highest compressive strength (p<0.05). Materials did not completely neutralize the bacterial biofilm, but the association with HAn provided greater bacterial reduction than MTA and PC+ZrO2 (p<0.05) after the post manipulation period of 2 days. CONCLUSIONS: The addition of HAn to PC associated with ZrO2 harmed the compressive strength and solubility. On the other hand, HAn did not change the pH and the initial setting time, but improved the radiopacity (HAn 10%), the final setting time and the E. faecalis antibiofilm activity of the cement. PMID- 27383701 TI - Effect of green tea extract on bonding durability of an etch-and-rinse adhesive system to caries-affected dentin. AB - OBJECTIVE: Green tea extract has been advocated as a matrix metalloproteinase (MMP) inhibitor; however, its effect on bond durability to caries-affected dentin has never been reported. Thus, the aim of this in vitro study was to evaluate the effect of two MMP inhibitors (2% chlorhexidine and 2% green tea extract), applied after acid etching, on bond durability of an etch-and-rinse adhesive system to caries-affected dentin. MATERIAL AND METHODS: Occlusal enamel was removed from third molars to expose the dentin surface, and the molars were submitted to a caries induction protocol for 15 days. After removal of infected dentin, specimens were conditioned with 37% phosphoric acid (15 seconds) and randomly divided into three groups, according to the type of dentin pretreatment (n=10): NT: no treatment; GT: 2% green tea extract; CLX: 2% chlorhexidine. The etch-and rinse adhesive system (AdperTM Single Bond 2, 3M ESPE, St. Paul, MN, USA) was applied according to the manufacturer's instructions, and composite resin restorations were built on the dentin. After 24 hours, at 37 degrees C, the resin tooth blocks were sectioned perpendicularly to the adhesive interface in the form of sticks (0.8 mm2 of adhesive area) and randomly subdivided into two groups according to when they were to be submitted to microtensile bond strength (MUTBS) testing: immediately or 6 months after storage in distilled water. Data were reported in MPa and submitted to two-way ANOVA for completely randomized blocks, followed by Tukey's test (alpha=0.05). RESULTS: After 24 hours, there was no significant difference in the MUTBS of the groups. After 6 months, the GT group had significantly higher MUTBS values. CONCLUSION: It was concluded that the application of 2% green tea extract was able to increase bond durability of the etch-and-rinse system to dentin. Neither the application of chlorhexidine nor non treatment (NT - control) had any effect on bond strength after water storage. PMID- 27383702 TI - Selective 5-HT7 receptor agonists LP 44 and LP 211 elicit an analgesic effect on formalin-induced orofacial pain in mice. AB - OBJECTIVE: To investigate the antinociceptive effects of pharmacological activation of 5-HT7 receptors on orofacial pain in mice. MATERIAL AND METHODS: Nociception was evaluated by using an orofacial formalin test in male Balb-C mice. Selective 5-HT7 receptor agonists, LP 44 and LP 211 (1, 5, and 10 mg/kg), were given intraperitoneally 30 min prior to a formalin injection. A bolus of 10 ul of 4% subcutaneous formalin was injected into the upper lip of mice and facial grooming behaviors were monitored. The behavioral responses consisted of two distinct periods, the early phase corresponding to acute pain (Phase I: 0-12 min) and the late phase (Phase II: 12-30 min). RESULTS: LP 44 and LP 211 (1, 5, and 10 mg/kg) produced an analgesic effect with reductions in face rubbing time in both Phase I and Phase II of the formalin test. CONCLUSION: Our results suggest that 5 HT7 receptor agonists may be promising analgesic drugs in the treatment of orofacial pain. PMID- 27383703 TI - CO2 laser and/or fluoride enamel treatment against in situ/ex vivo erosive challenge. AB - OBJECTIVE: This in situ/ex vivo study investigated the effect of CO2 laser irradiation and acidulated phosphate fluoride gel (APF) application, separately and in combination, on enamel resistance to erosion. MATERIAL AND METHODS: During 2 experimental 5-day crossover phases, 8 volunteers wore intraoral appliances containing bovine enamel blocks which were submitted to four groups: 1st phase - control, untreated and CO2 laser irradiation, 2nd phase - fluoride application and fluoride application before CO2 laser irradiation. Laser irradiation was performed at 10.6 um wavelength, 5 us pulse duration and 50 Hz frequency, with average power input and output of 2.3 W and 2.0 W, respectively (28.6 J/cm2). APF gel (1.23%F, pH 3.5) was applied on enamel surface with a microbrush and left on for 4 minutes. Then, the enamel blocks were fixed at the intraoral appliance level. The erosion was performed extraorally 4 times daily for 5 min in 150 mL of cola drink. Enamel loss was measured profilometrically after treatment and after the in situ phase. The data were tested using one-way Repeated Measures Anova and Tukey's test (p<0.05). RESULTS: CO2 laser alone (2.00+/-0.39 um) did not show any significantly preventive effect against enamel erosion when compared with the control group (2.41+/-1.20 um). Fluoride treated enamel, associated (1.50+/-0.30 um) or not (1.47+/-0.63 um) with laser irradiation, significantly differed from the control. CONCLUSION: The APF application decreased enamel wear; however, CO2 laser irradiation did not enhance fluoride ability to reduce enamel wear. PMID- 27383704 TI - Frequency of periodontal pathogens and Helicobacter pylori in the mouths and stomachs of obese individuals submitted to bariatric surgery: a cross-sectional study. AB - OBJECTIVES: This cross-sectional study compared the frequency of oral periodontopathogens and H. pylori in the mouths and stomachs of obese individuals with or without periodontitis submitted to bariatric surgery. MATERIAL AND METHODS: One hundred and fifty-four men and women aged 18-65 were conveniently distributed into four groups. Two groups were composed of individuals who underwent bariatric surgery with (BP) (n=40) and without (BNP) (n=39) periodontitis and two obese control groups with (CP) (n=35) and without (CNP) (n=40) periodontitis. The oral pathogens Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Parvimonas micra, Treponema denticola, Tannerella forsythia, Campylobacter rectus, and Helicobacter pylori were detected by a polymerase chain reaction technique using saliva, tongue and stomach biopsy samples. RESULTS: Statistical analysis demonstrated that periodontopathogens were highly frequent in the mouth (up to 91.4%). In the bariatric surgically treated group, orally, P. gingivalis, T. denticola and T. forsythia were more frequent in periodontitis, while C. rectus was more frequent in non-periodontitis subjects. Stomach biopsies also revealed the high frequency of five oral species in both candidates for bariatric surgery (91.6%) and the bariatric (83.3%) groups. H. pylori was frequently detected in the mouth (50.0%) and stomach (83.3%). In the stomach, oral species and H. pylori appeared in lower frequency in the bariatric group. CONCLUSIONS: Obese individuals showed high frequencies of periodontopathogens and H. pylori in their mouths and stomachs. Bariatric surgery showed an inverse microbial effect on oral and stomach environments by revealing higher oral and lower stomach bacterial frequencies. PMID- 27383705 TI - The effects of supplemental melatonin administration on the healing of bone defects in streptozotocin-induced diabetic rats. AB - OBJECTIVE: The aim of this study was to investigate histologic and biochemical effects of supplemental melatonin administration on bone healing and antioxidant defense mechanism in diabetic rats. MATERIAL AND METHODS: Eighty-six Sprague Dawley male rats were used in this study. Diabetes mellitus was induced by intraperitoneal (i.p.) administration of 65 mg/kg streptozotocin (STZ). Surgical bone defects were prepared in the tibia of each animal. Diabetic animals and those in control groups were treated either with daily melatonin (250 MUg/animal/day/i.p.) diluted in ethanol, only ethanol, or sterile saline solution. Rats were humanely killed at the 10th and 30th postoperative days. Plasma levels of Advanced Oxidation Protein Products (AOPP), Malondialdehyde (MDA), and Superoxide Dismutase (SOD) were measured. The number of osteoblasts, blood vessels and the area of new mineralized tissue formation were calculated in histologic sections. RESULTS: At the 10th day, DM+MEL (rats receiving both STZ and melatonin) group had significantly higher number of osteoblasts and blood vessels as well as larger new mineralized tissue surfaces (p<0.05 for each) when compared with DM group. At the 30th day, DM group treated with melatonin had significantly lower levels of AOPP and MDA than those of DM group (p<0.05). CONCLUSION: Melatonin administration in STZ induced diabetic rats reduced oxidative stress related biomarkers and showed beneficial effects on bone healing at short term. PMID- 27383706 TI - Liver proteome of mice with different genetic susceptibilities to the effects of fluoride. AB - OBJECTIVE: In this study, we investigated the differential pattern of protein expression in the liver of these mice to provide insights on why they have different responses to F. MATERIAL AND METHODS: Weanling male A/J and 129P3/J mice (n=10 from each strain) were pared and housed in metabolic cages with ad libitum access to low-F food and deionized water for 42 days. Liver proteome profiles were examined using nLC-MS/MS. Protein function was classified by GO biological process (Cluego v2.0.7 + Clupedia v1.0.8) and protein-protein interaction network was constructed (PSICQUIC, Cytoscape). RESULTS: Most proteins with fold change were increased in A/J mice. The functional category with the highest percentage of altered genes was oxidation-reduction process (20%). Subnetwork analysis revealed that proteins with fold change interacted with Disks large homolog 4 and Calcium-activated potassium channel subunit alpha-1. A/J mice had an increase in proteins related to energy flux and oxidative stress. CONCLUSION: This could be a possible explanation for the high susceptibility of these mice to the effects of F, since the exposure also induces oxidative stress. PMID- 27383707 TI - Comparative in vitro evaluation of CAD/CAM vs conventional provisional crowns. AB - OBJECTIVE: This study compared the marginal gap, internal fit, fracture strength, and mode of fracture of CAD/CAM provisional crowns with that of direct provisional crowns. MATERIAL AND METHODS: An upper right first premolar phantom tooth was prepared for full ceramic crown following tooth preparation guidelines. The materials tested were: VITA CAD-Temp(r), Polyetheretherketone "PEEK", Telio CAD-Temp, and ProtempTM4 (control group). The crowns were divided into four groups (n=10), Group1: VITA CAD-Temp(r), Group 2: PEEK, Group 3: Telio CAD-Temp, and Group 4: ProtempTM4. Each crown was investigated for marginal and internal fit, fracture strength, and mode of fracture. Statistical analysis was performed using GraphPad Prism software version 6.0. RESULTS: The average marginal gap was: VITA CAD-Temp(r) 60.61 (+/-9.99) um, PEEK 46.75 (+/-8.26) um, Telio CAD-Temp 56.10 (+/-5.65) um, and ProtempTM4 193.07(+/-35.96) um (P<0.001). The average internal fit was: VITA CAD-Temp(r) 124.94 (+/-22.96) um, PEEK 113.14 (+/-23.55) um, Telio CAD-Temp 110.95 (+/-11.64) um, and ProtempTM4 143.48(+/-26.74) um. The average fracture strength was: VITA CAD-Temp(r) 361.01 (+/-21.61) N, PEEK 802.23 (+/-111.29) N, Telio CAD-Temp 719.24 (+/-95.17) N, and ProtempTM4 416.40 (+/ 69.14) N. One-way ANOVA test showed a statistically significant difference for marginal gap, internal gap, and fracture strength between all groups (p<0.001). However, the mode of fracture showed no differences between the groups (p>0.05). CONCLUSIONS: CAD/CAM fabricated provisional crowns demonstrated superior fit and better strength than direct provisional crowns. PMID- 27383708 TI - Speech perception and quality of life of open-fit hearing aid users. AB - OBJECTIVE: To relate the performance of individuals with hearing loss at high frequencies in speech perception with the quality of life before and after the fitting of an open-fit hearing aid (HA). METHODS: The WHOQOL-BREF had been used before the fitting and 90 days after the use of HA. The Hearing in Noise Test (HINT) had been conducted in two phases: (1) at the time of fitting without an HA (situation A) and with an HA (situation B); (2) with an HA 90 days after fitting (situation C). STUDY SAMPLE: Thirty subjects with sensorineural hearing loss at high frequencies. RESULTS: By using an analysis of variance and the Tukey's test comparing the three HINT situations in quiet and noisy environments, an improvement has been observed after the HA fitting. The results of the WHOQOL BREF have showed an improvement in the quality of life after the HA fitting (paired t-test). The relationship between speech perception and quality of life before the HA fitting indicated a significant relationship between speech recognition in noisy environments and in the domain of social relations after the HA fitting (Pearson's correlation coefficient). CONCLUSIONS: The auditory stimulation has improved speech perception and the quality of life of individuals. PMID- 27383709 TI - Effects of budlein A on human neutrophils and lymphocytes. AB - OBJECTIVE: In this study, we evaluated whether budlein A modulates the activation of innate and adaptive immune cells such as neutrophils and lymphocytes. MATERIAL AND METHODS: Our research group has investigated several plant species and several compounds have been isolated, identified, and their medical potential evaluated. Budlein A is a SL isolated from the species Aldama buddlejiformis and A. robusta (Asteraceae) and shows anti-inflammatory and anti-nociceptive activities. Advances in understanding how plant-derived substances modulate the activation of innate and adaptive immune cells have led to the development of new therapies for human diseases. RESULTS: Budlein A inhibited MPO activity, IL-6, CXCL8, IL-10, and IL-12 production and induces neutrophil apoptosis. In contrast, budlein A inhibited lymphocyte proliferation and IL-2, IL-10, TGF-beta, and IFN gamma production, but it did not lead to cell death. CONCLUSIONS: Collectively, our results indicate that budlein A shows distinct immunomodulatory effects on immune cells. PMID- 27383710 TI - TNF-alpha expression, evaluation of collagen, and TUNEL of Matricaria recutita L. extract and triamcinolone on oral ulcer in diabetic rats. AB - OBJECTIVE: to evaluate the influence of Tumor Necrosis Factor alpha (TNF-alpha) and apoptosis in rats with DM treated with chamomile extract or triamcinolone. MATERIAL AND METHODS: Wistar male rats (210.0+/-4.2 g) were divided into five groups: negative control group (NCG) without diabetes; positive control group (PCG) with DM (alloxan, 45 mg/kg); and groups treated with chamomile extract (normoglycemic= NCG group and diabetic= DCG group) and with triamcinolone (TG). Traumatic ulcers were performed on all animals that received topical triamcinolone, chamomile extract or saline 12/12 hours for ten days. RESULTS: On days five and ten the animals were euthanized and the ulcers were analyzed by light microscopy, TUNEL assay, and immunohistochemically (TNF-alpha). The NCG (p=0.0062), PCG (p=0.0285), NCG (p=0.0041), and DCG (p<0.0001) groups were completely healed on the 10th day, however, there was no healing on the TG (p=0.5127) group. The TNF-alpha expression showed a significant reduction from the 5th to the 10th day in NCG (p=0.0266) and DCG (p=0.0062). In connective tissue, the TUNEL assay showed a significant reduction in the number of positive cells in NCG (p=0.0273) and CNG (p=0.0469) and in the epithelium only in CDG (p=0.0320). CONCLUSIONS: Chamomile extract can optimize the healing of traumatic oral ulcers in diabetic rats through the reduction of apoptosis in the epithelium and TNF-alpha expression. PMID- 27383711 TI - Tissue dissolution and modifications in dentin composition by different sodium hypochlorite concentrations. AB - OBJECTIVES: To determine the organic matter dissolution and changes in dentin chemical composition promoted by different concentrations of NaOCl over time. MATERIAL AND METHODS: Fragments of bovine muscle tissue were weighed before and after 5, 10, and 15 min of immersion in the groups (n=10): G1- 0.9% saline solution; G2- 1% NaOCl; G3- 2.5% NaOCl; and G4- 5% NaOCl. Bovine dentin fragments were subjected to the same irrigants and absorption spectra were collected by Attenuated Total Reflectance of Fourier Transform Infrared Spectroscopy (ATR FTIR) before and after 0,5, 1, 2, 3, 5, 8, and 10 min of immersion in the solutions. The ratios of the amide III/phosphate and carbonate/phosphate absorption bands were determined. The tissue dissolution and carbonate/phosphate ratios were submitted to the two-way analysis of variance (ANOVA) with Tukey's multiple-comparison test (alpha<0.05) and to the one-way analysis of variance with Tukey's (alpha<0.05). The amide III/phosphate ratio was analyzed by Friedman test (alpha<0.05) and the Kruskal-Wallis test with Dunn's post-hoc (alpha<0.05). RESULTS: The increase in NaOCl concentration and contact time intensified the dissolution of organic matter and dentin collagen with reduction in the amide III/phosphate ratio. Significant differences between all groups (p<0.05) were observed in the dissolution of organic matter at 10 min and in the amide III/phosphate ratio between the saline solution and 5% NaOCl at 5 min. The carbonate/phosphate ratio decreased significantly in G2, G3, and G4 after 0,5 min of immersion (p<0.05), but more alterations did not occur in the subsequent periods (p>0.05). Intergroup differences were not observed in this ratio (p>0.05). CONCLUSIONS: The increase in the exposure time and in the concentration of NaOCl solution lead to an increase in the tissue dissolution and dentin collagen deproteination. Furthermore, some carbonate ions are removed from the dentin inorganic phase by the NaOCl. PMID- 27383713 TI - Retraction. AB - [This corrects the article DOI: 10.1590/1678-775720150393.]. PMID- 27383712 TI - Fifty years of Brazilian Dental Materials Group: scientific contributions of dental materials field evaluated by systematic review. AB - OBJECTIVE: A systematic review was conducted to analyze Brazilian scientific and technological production related to the dental materials field over the past 50 years. MATERIAL AND METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (Prisma) statement. Searches were performed until December 2014 in six databases: MedLine (PubMed), Scopus, LILACS, IBECS, BBO, and the Cochrane Library. Additionally, the Brazilian patent database (INPI - Instituto Nacional de Propriedade Industrial) was screened in order to get an overview of Brazilian technological development in the dental materials field. Two reviewers independently analyzed the documents. Only studies and patents related to dental materials were included in this review. Data regarding the material category, dental specialty, number of documents and patents, filiation countries, and the number of citations were tabulated and analyzed in Microsoft Office Excel (Microsoft Corporation, Redmond, Washington, United States). RESULTS: A total of 115,806 studies and 53 patents were related to dental materials and were included in this review. Brazil had 8% affiliation in studies related to dental materials, and the majority of the papers published were related to dental implants (1,137 papers), synthetic resins (681 papers), dental cements (440 papers), dental alloys (392 papers) and dental adhesives (361 papers). The Brazilian technological development with patented dental materials was smaller than the scientific production. The most patented type of material was dental alloys (11 patents), followed by dental implants (8 patents) and composite resins (7 patents). CONCLUSIONS: Dental materials science has had a substantial number of records, demonstrating an important presence in scientific and technological development of dentistry. In addition, it is important to approximate the relationship between academia and industry to expand the technological development in countries such as Brazil. PMID- 27383715 TI - Social Support for Older Adults-A Bane or a Boon for their Health? PMID- 27383714 TI - Utilizing the micron sized non-thermal atmospheric pressure plasma inside the animal body for the tumor treatment application. AB - This study aimed to evaluate the effects of micron sized non-thermal atmospheric pressure plasma inside the animal body on breast cancer tumor. The MU-plasma jet consists of micron sized hollow tube in which pure helium gas is ionized by high voltage (4 kV) and high frequency (6 kHz). The efficiency of the plasma treatment in killing cancer cells was first investigated by cell viability measurements of treated 4T1 cells using flow cytometry and cell cycle analysis. For exploration of the in vivo effects of the plasma treatment, the BALB/c mice inoculated by 4T1 cell lines were exposed subcutaneously to plasma for 3 minutes. In addition, H&E staining, TUNEL and Western blotting assays were performed in order to observed the effects of the non-thermal plasma on the tumor cells. The results showed that the efficiency of the plasma in suppression of the tumor growth is comparable to that of a typical chemotherapy drug. Moreover, the results indicated that the plasma induces apoptosis in the tumor tissue and increases the ratio of the apoptotic to anti-apoptotic protein expression. We believe that these findings presented herein may extend our knowledge of the mechanisms by which the plasma exerts its promising anti-cancer effects. PMID- 27383716 TI - Prevalence and Correlates of Internet Gaming Problem among Internet Users: Results from an Internet Survey. AB - INTRODUCTION: The current study aimed to establish the prevalence of internet gaming disorder (IGD) and its association with demographic characteristics, game genre, game use (time spent on gaming), as well as psychological distress, social phobia and well-being among current online gamers in Singapore. MATERIALS AND METHODS: A total of 1251 participants aged 13 to 40 years completed the study which was administered as a web survey. The online questionnaire was designed using QuestionPro, and consisted of 8 sections and 105 questions. The 9-item Internet Gaming Disorder Questionnaire was used to establish the prevalence of IGD in the study. A series of logistic regression models were used to examine the associations between IGD, demographic characteristics and game genre, as well as IGD and psychological distress, social phobia and well-being. RESULTS: The prevalence of IGD established using a cutoff of 5 among those who were current online gamers was 17.7%. Multiple logistic regressions revealed that those meeting criteria of IGD were more likely to be older, reported an earlier age of onset of playing online games, had primary and secondary education versus tertiary education, were currently students versus being currently employed and played massively multiplayer online role-playing games. Distress and social anxiety were higher while satisfaction with life was significantly lower among those who met criteria for IGD than those who did not meet the criteria. CONCLUSION: The prevalence of IGD and its negative consequences in our sample of current online gamers was significant and point towards the need for further clinical studies and innovative interventions to address the problem. PMID- 27383717 TI - Prevalence of Tobacco Smoking and Accuracy of Self-Reporting in Pregnant Women at a Public Hospital for Women and Children. AB - INTRODUCTION: Denial of smoking status by pregnant women presents a missed opportunity for referral to smoking cessation programmes that are shown to be effective in helping them quit smoking. MATERIALS AND METHODS: A cross-sectional epidemiological survey was conducted to detect the true prevalence of active smoking pregnant patients and the accuracy of self-reporting, investigate the sociodemographic risk factors and test the knowledge of pregnant patients on adverse effects of smoking. This involved 972 antenatal patients of a maternity hospital where participants completed a sociodemographic data survey and answered a knowledge questionnaire. Urine cotinine testing was carried out after informed consent. RESULTS: The prevalence of active smokers was 5.2% (n = 50) with 3% (n = 29) being light smokers and 2.2% (n = 21) being heavy smokers. This was significantly higher than self-reported active smoking status of 3.7% (n = 36; P = 0.02). The Malay race, being aged less than 20 years and not having tertiary level qualifications independently increased the likelihood of being an active smoker. Knowledge of the adverse effects of smoking was generally good with a mean total score of 8.18 out of 10 but there were differences amongst the non smokers, passive smokers, light smokers and active smokers (P = 0.012). CONCLUSION: While the prevalence of active smoking among pregnant women is low in Singapore compared to other countries, this study substantiated the unreliability of self-reporting of smoking status in the pregnant population which could complicate referral to smoking cessation programmes. The lower awareness of the harms of smoking during pregnancy among smokers highlights a potential area for improvement. PMID- 27383718 TI - A Retrospective Review of Imaging and Operative Modalities Performed in Patients with Primary Hyperparathyroidism at a Mid-Volume Surgical Centre in Southeast Asia. AB - INTRODUCTION: A paradigm shift appears to have occurred worldwide in surgery for primary hyperparathyroidism with the advent of sensitive preoperative imaging techniques. Preoperative imaging for parathyroid adenoma localisation was not found to be useful in a study conducted in Singapore in the 1990s. This study aimed to explore what the change has been in preoperative localisation tools compared to the previous study and if the ability of these tools to correctly localise pathologic parathyroid glands has improved. MATERIALS AND METHODS: A retrospective review of patients who had surgery for primary hyperparathyroidism at our institution during the period 2005 to 2014 was carried out. Individuals with positive, as opposed to those with negative preoperative imaging, were compared with regard to whether they underwent limited focal or bilateral neck exploration. Length of hospital stay (LOHS) was also compared between patients who underwent limited versus bilateral exploration. RESULTS: Fifty-eight patients who had preoperative imaging and surgery were evaluated. True positive rates of sestamibi, ultrasound and 4-dimensional (4D) computed tomography (CT) scans were 63.8%, 72.4% and 90%, respectively. Eighty percent of patients who had positive localisation had limited exploration. LOHS was 2.8 days (1.6, 4.8) and 4.3 days (2.1, 9.0) for limited and bilateral exploration respectively, P = 0.011. CONCLUSION: Our study highlights the marked change in the surgical landscape for primary hyperparathyroidism in the last 2 decades in Singapore. Improved preoperative localisation has resulted in a swing from predominantly bilateral, to limited exploration in almost all cases of primary hyperparathyroidism due to solitary adenoma. LOHS was significantly shorter in patients who had limited as compared to those who had bilateral exploration. PMID- 27383719 TI - The Impact of Education Reform: An Asian Medical School's Experience. AB - This study assessed the effectiveness of education reforms on student-reported learning outcomes at the end of the 5-year medical school (M5) and 1-year internship (HO) in 2006, 2007 and 2008. A self-administered anonymous survey with 17 learning outcomes assessed, derived from Harden's Three-Circle Outcomes Model for outcomes-based education, was administered to 683 students at the end of medical school (M5) and internship (HO) from 2006, 2007 and 2008. We identified learning outcomes which changed significantly for internship (Cohorts A, B and C) and medical school (Cohorts B, C and D) between cohorts from 2006 to 2008, and compared learning outcomes between medical school and internship within cohorts (i.e. Cohort B which was M5 in 2006 and HO in 2007; Cohort C which was M5 in 2007 and HO in 2008). The proportion of students who agreed that medical school helped them achieve learning outcomes increased significantly from 2006 to 2008 for 15 out of 17 learning outcomes assessed. The proportion of students who agreed that internship helped them achieve learning outcomes increased significantly from 2006 to 2008 for 6 learning outcomes assessed. For Cohorts B and C, internship was more effective than medical school in achieving 8 learning outcomes. Cohort C reported that internship was more effective than medical school in 3 additional learning outcomes than Cohort B: patient management, humility and dedication. We conclude that a successful journey of education reform is an ongoing process that needs to comprehensively address multifaceted components such as faculty, administration and curriculum. PMID- 27383720 TI - Enhancing Doctors' and Healthcare Professionals' Patient-care Role through Actor training: Workshop Participants' Responses. PMID- 27383721 TI - Are We Working Too Hard?-A Functional Scoring of Orthopaedic Surgeons. PMID- 27383722 TI - The Prevalence of Post-Traumatic Stress Disorder in Intensive Care Unit Staff and the Common Coping Strategies Used. PMID- 27383723 TI - Dermatologic Screening in an Elderly Community with Low Socioeconomic Status in Singapore. PMID- 27383724 TI - Nerve Transfer for Elbow Extension in Obstetrical Brachial Plexus Palsy. PMID- 27383725 TI - On the Route to the Photogeneration of Heteroaryl Cations. The Case of Halothiophenes. AB - 2-Chloro-, 2-bromo-, and 2-iodothiophenes undergo photochemical dehalogenation via the triplet state. In the presence of suitable pi-bond nucleophiles, thienylation occurs with modest yield from chloro and bromo derivatives (via photogenerated triplet 2-thienyl cation). Specific trapping by using oxygen along with computational analysis carried out by means of a density functional method support that, in the case of iodo derivatives, homolytic thienyl-I bond fragmentation occurs first and heteroaryl cations are formed by electron transfer within the triplet radical pair, thus opening an indirect access to such cations. PMID- 27383726 TI - Tuberculosis and non-tuberculous mycobacteria among HIV-infected individuals in Ghana. AB - OBJECTIVES: To assess the prevalence and clinical importance of previously unrecognised tuberculosis (TB) and isolation of non-tuberculous mycobacteria (NTM) among HIV-infected individuals in a teaching hospital in Ghana. METHODS: Intensified mycobacterial case finding was conducted among HIV-positive individuals before initiation of antiretroviral therapy (ART). Data were collected on socio-demographic characteristics, medical history and TB-related signs and symptoms, and participants were followed for six months to determine treatment and vital status. Two sputum samples were obtained and examined for mycobacteria with smear microscopy, culture and Xpert MTB/RIF assay. NTM species were identified with the GenoType Mycobacterium CM/AS or sequence analysis of 16S rRNA gene. RESULTS: Of 473 participants, 60 (12.7%) had confirmed pulmonary TB, and 38 (8.0%) had positive cultures for NTM. Mycobacterium avium complex was identified in 9/38 (23.7%) of NTM isolates. Participants with NTM isolated were more likely to have CD4 cell count< 100 cells/MUL (aOR 2.37; 95% CI: 1.10-5.14), BMI<18.5kg/m(2) (aOR 2.51; 95% CI: 1.15-5.51) and fever >=2 weeks (aOR 2.76; 95% CI: 1.27-6.03) at baseline than participants with no mycobacteria. By six months, 76 (16.1%) participants had died; 20 (33.3%) with confirmed TB and 9 (23.7%) with NTM-positive culture. Mortality at six months was independently associated with TB diagnosis at enrolment (aHR 1.97; 95% CI 1.09-3.59), but not with NTM isolation after controlling for age, sex, CD4 cell count, BMI, prolonged fever and ART initiation. CONCLUSIONS: Intensified mycobacterial screening of HIV infected individuals revealed a high burden of unrecognised pulmonary TB before ART initiation, which increased risk of death within six months. NTM were frequently isolated and associated with signs of poor clinical status but not with increased mortality. PMID- 27383727 TI - Electrochemical Surface Interrogation of a MoS2 Hydrogen-Evolving Catalyst: In Situ Determination of the Surface Hydride Coverage and the Hydrogen Evolution Kinetics. AB - The hydrogen evolution reaction (HER) on an electrodeposited a-MoS2 electrode was investigated by a surface-selective electrochemical titration technique by application of surface interrogation scanning electrochemical microscopy. In a mildly acidic (pH 4.6) environment, the saturated surface hydride coverage of MoS2 was determined to be 31%, much higher than that expected for a crystalline nanoparticle. The HER rate constant of a surface molybdenum atom was measured for the first time in situ to be 3.8 s(-1) at a 600 mV overpotential. At high Mo-H coverages, a change in the nature of the active sites was observed upon consumption of Mo-H by HER. PMID- 27383728 TI - Keeping FIT, storing fat: Lipid droplet biogenesis. AB - All eukaryotes store excess lipids in organelles known as lipid droplets (LDs), which play central roles in lipid metabolism. Understanding LD biogenesis and metabolism is critical for understanding the pathophysiology of lipid metabolic disorders like obesity and atherosclerosis. LDs are composed of a core of neutral lipids surrounded by a monolayer of phospholipids that often contains coat proteins. Nascent LDs bud from the endoplasmic reticulum (ER) but the mechanism is not known. In this commentary we discuss our recent finding that a conserved family of proteins called fat storage-inducing transmembrane (FIT) proteins is necessary for LDs budding from the ER. In cells lacking FIT proteins, LDs remain in the ER membrane. C. elegans has a single FIT protein (FITM-2), which we found is essential; almost all homozygous fitm-2 animals die as larvae and those that survive to adulthood give rise to embryos that die as L1 and L2 larvae. Homozygous fitm-2 animals have a number of abnormalities including a significant decrease in intestinal LDs and dramatic defects in muscle development. Understanding how FIT proteins mediate LD biogenesis and what roles they play in lipid metabolism and development are fascinating challenges for the future. PMID- 27383729 TI - A mechanical pencil lead-supported carbon nanotube/Au nanodendrite structure as an electrochemical sensor for As(iii) detection. AB - A mechanical pencil lead (MPL), an easily obtainable carbon-based material with a consistent size, was used as a frame to construct an MPL-supported carbon nanotube/Au nanodendrite (MPL-CNT/AuND) sensor through simple electrodeposition of Au onto the MPL in the presence of CNTs. A nanodendrite structure was adopted to ensure large numbers of active electrochemical sites because of its hierarchical structure with well-aligned terraces; the CNTs were used to firmly adhere the fabricated Au nanodendrites to the MPL surface to ensure ruggedness. The MPL-CNT/AuND structure was used to measure As3+ samples in a concentration range from 0.5 to 80 ppb using anodic stripping voltammetry (ASV). The variation in peak intensities was linear (R2: 0.997), and the limit of detection (LOD) was 0.4 ppb. The average relative standard deviation (RSD) of the peak intensities from the voltammograms of each sample collected using three separately prepared MPL-CNT/AuNDs was 8.7%, thereby demonstrating good sensor-to-sensor reproducibility. Furthermore, when three As3+ samples prepared in tap water were measured, the accuracy was maintained without noticeable degradation and the response was steady up to 50-cycle measurements. PMID- 27383730 TI - Aerosol Nanoencapsulation: Single-Pass Floating Self-Assembly of Biofunctional Hybrid Nanoplatforms. AB - Multifunctional nanoplatforms were prepared via floating self-assembly using a hard nanoparticle (NP) as the core and a modified-polymer (MP, cholesterol chitosan linked with polyethylenimine) droplet as the shell in a single-pass aerosol nanoencapsulation process. The floating hard NPs (silica, calcium carbonate, gold-decorated graphene oxide, and thiol-capped gold) were directly injected into MP droplets at the opening of a spraying device. Subsequently, the solvent was thermally extracted from the droplets, resulting in the formation of biofunctional nanoplatforms. Measured in vitro, the genes complexed with the nanoplatforms were transfected into target cells, exhibiting higher efficiencies for the MP particles alone without a significant increase in in vitro cell cytotoxicity. The aerosol encapsulation could be further extended to prepare other combinations [gold-silica and gold-calcium carbonate including doxorubicin (Dox)] using the MP, and their hybrid natures demonstrated photothermal cancer cell killing and chemo-thermal Dox release capabilities through surface plasmon resonance heating. PMID- 27383731 TI - Investigation of Solute-Fiber Affinity and Orientational Ordering of Norbornadiene Interacting with Two-Polypeptide Chiral Liquid Crystalline Solvents by Natural Abundance Deuterium (NAD) NMR. AB - A prochiral bridged compound of C2v symmetry, the norbornadiene (NBD), oriented in a chiral liquid crystal composed of various mixtures of poly-gamma-benzyl-l glutamate (PBLG) and poly-epsilon-carboxy-l-lysine (PCBLL), two chiral homopolypeptides, is investigated using natural abundance deuterium 2D-NMR (NAD 2D-NMR) spectroscopy. In such chiral oriented solvents, enantiotopic directions are spectrally nonequivalent, and two distinct (2)H quadrupolar doublets associated with enantioisotopomeric pairs of NBD are detected. As the two homopolypeptides have the same absolute configuration but distinct chemical functions in their side chains, the variation of residual quadrupolar couplings (RQC's) allows the determination of the relative solute-fiber affinities toward the two polypeptides in these lyotropic bipolymeric systems. Besides the experimental measurement of RQC's and the determination of their signs at each inequivalent (2)H site, the elements of the second-rank order tensor, Salphabeta, are calculated by assuming a modeled structure. The variations of RQC's and diagonalized order parameters, Salpha'alpha', are followed versus the relative proportion of two polypeptides in the chiral oriented mixture. The influence of the solute mass fraction in the two-homopolypeptide oriented samples is also examined as well as the case of homogeneous and uniform achiral mesophases "PBG PCBL" made of two pairs of mirror-image homopolypeptides (PBLG/PBDG and PCBLL/PCBDL). In the latter, the solute ordering is modulated by the proportion of each type of homopolypeptide (chemical nature and absolute configuration), leading to eliminate the enantiodiscrimination mechanisms on the average. In the frame of a model, new insights on the solute-homopolypeptide fiber interactions are discussed. PMID- 27383732 TI - Association Between Enoxaparin Dosage Adjusted by Anti-Factor Xa Trough Level and Clinically Evident Venous Thromboembolism After Trauma. AB - Importance: Trauma patients are at high risk for developing venous thromboembolism (VTE). The VTE rate when enoxaparin sodium is dosed by anti factor Xa (anti-Xa) trough level is not well described. Objective: To determine whether targeting a prophylactic anti-Xa trough level by adjusting the enoxaparin dose would reduce the VTE rate in trauma patients. Design, Setting, and Participants: Single-institution, historic vs prospective cohort comparison study at an urban, academic, level I trauma center. The prospective cohort was enrolled from August 2014 to May 2015 and compared with a historic cohort admitted from August 2013 to May 2014. Trauma patients who received enoxaparin adjusted by anti Xa trough level (adjustment group) were compared with those who received enoxaparin sodium at a dosage of 30 mg twice daily (control group). Patients were excluded if they were younger than 18 years, had a length of hospital stay less than 2 days, or had preexisting deep vein thrombosis. Patients were excluded from the adjustment group for changes in the choice of thromboprophylaxis (heparin, enoxaparin once-daily dosing, early ambulation), hospital discharge before initial trough levels could be drawn, or incorrect timing of trough levels. Exposures: Anti-Xa trough levels were monitored in patients in the adjustment group receiving 3 or more consecutive doses of enoxaparin sodium, 30 mg twice daily. Patients with a trough level of 0.1 IU/mL or lower received enoxaparin sodium increased by 10-mg increments. After providing 3 adjusted doses of enoxaparin, the trough level was redrawn and the dosage was adjusted as necessary. Patients in the control group received enoxaparin sodium at a dosage of 30 mg twice daily without adjustments. Main Outcomes and Measures: Rates of symptomatic VTE (deep vein thrombosis and pulmonary embolism, confirmed by duplex ultrasonography and chest computed tomographic angiography, respectively) and bleeding risk. Results: A total of 205 patients (mean [SD] age, 41.3 [18.2] years; 75.1% male) were studied, 87 in the adjustment group and 118 in the control group, with similar baseline characteristics and injury profiles. Subprophylactic anti-Xa troughs were noted in 73 of 87 patients (83.9%) in the adjustment group, and the majority of patients (57 of 87 patients [65.5%]) required dosage adjustment of enoxaparin sodium to 40 mg twice daily. Incidence of VTE was significantly lower in the adjustment group than in the control group (1.1% vs 7.6%, respectively; P = .046). When the adjustment group was compared with the control group, no significant difference was noted in the rate of packed red blood cell transfusion (6.9% vs 12.7%, respectively; P = .18) or mean (SD) hematocrit at discharge (34.5% [6.3%] vs 33.4% [6.8%], respectively [to convert to proportion of 1.0, multiply by 0.01]; P = .19). Conclusions and Relevance: In this study, subprophylactic anti-Xa trough levels were common in trauma patients. Enoxaparin dosage adjustment may lead to a reduced rate of VTE without an increased risk of bleeding. PMID- 27383733 TI - The rising incidence of papillary thyroid microcarcinoma and is completion surgery necessary or not? AB - Papillary thyroid microcarcinoma (PTMC) is defined as a papillary cancer that is 1 cm or less in its maximal diameter. The incidence of thyroid cancer has increased during the past 30 years. The aim of this study is to evaluate the rising incidence of PTMC (papillary thyroid microcarcinoma) and whether is lobectomy enough or not. The data of 462 consecutive patients who underwent thyroidectomy (hemithyroidectomy and total thyroidectomy) at the Hacettepe University Hospitals Department of ENT from 2000 to 2015 were analyzed. Surgical procedure, histopathologic examinations, postoperative complications, follow-up time and mortality were recorded. USG and FNAC were performed on all cases. Of the 344 patients with thyroid malignancy and 118 patients underwent total laryngectomy with thyroidectomy. 364 patients with TT and 98 patients with HT. The first group included 204 patients (Surgery time 2000-2007), 91 of them ( 44.6%) had PTMC. The second group included 258 patients, 192of them (74,4%) had PTMC (p<0.001). 22 Patients with PTMC underwent completion surgery and 40 of them just followed by hemithyroidectomy. There was no recurrence. PTMC has been rising incidence because of ,pathological and radiological, increased awareness and completion surgery is not necessary for all PTMC cases especially incidental PTMC. PMID- 27383734 TI - Analysis of hearing improvement in the patients operated on due to otosclerosis in the Otolaryngology Department of Jagiellonian University of Cracow, Poland. AB - BACKGROUND: Otosclerosis is the most common cause of condactive hearing loss between 15 and 50 years old. The most common symptoms are hearinglosss and tinnitus. Surgery is currently the preferred treatment method. AIM: The aim of our study was to analyze the outcomes of patients treated surgically due to otosclerosis in terms of the observed changes in pure tone audiometry and speech audiometryMaterial and methods:We observated 300 patients operated on middle ear for the fist time in the Department of Otolarygology at the Jagiellonian University of Cracow from 2010 to 2011. We used a special questinnaire which includes diagnostics of the ears disease,pure tone audiometry, speech audiometrii and longterm effects. RESULTS: We discuss 53 operated ears and analyze changes in pure tone audiometry. We divided patients into 2 groups depending on 100% speech understanding in speech auodiometry or not. CONCLUSION: 1. Lack of 100% speech understanding in speech audiometry correlated with greater sensorineural hearing loss than in patients who achieved 100% speech understanding prior to surgery. 2. Lack of 100% speech understanding in speech audiometry is a predictive factor for worse prognosis in improving hearing in patients operated on for otosclerosis. 3. Reconstruction of the ossicular chain in patients, regardless of the degree of speech understanding, did not produce significant changes in the average values of bone conduction. PMID- 27383736 TI - Advantages and disadvantages of the Belgian not-only-fault system for medical incidents. AB - In 2010, the Belgian compensation system for medical incidents was reformed, in order to overcome some important deficiencies of court procedures. This resulted in a not-only-fault compensation system, following the establishment of the Fund for Medical Accidents (FMA). This paper seeks to clarify the main advantages and disadvantages of this reform. After all, the legislator paid little attention to the impact on physicians, who also seem to be insufficiently informed. However, currently the FMA experiences a significant delay in processing compensation requests. The true effects of the not-only-fault system for patients and physicians as well as for health care quality therefore still remain unclear today. PMID- 27383735 TI - Importance of mosquito "quasispecies" in selecting an epidemic arthropod-borne virus. AB - Most arthropod-borne viruses (arboviruses), perpetuated by alternation between a vertebrate host and an insect vector, are likely to emerge through minor genetic changes enabling the virus to adapt to new hosts. In the past decade, chikungunya virus (CHIKV; Alphavirus, Togaviridae) has emerged on La Reunion Island following the selection of a unique substitution in the CHIKV E1 envelope glycoprotein (E1 A226V) of an East-Central-South African (ECSA) genotype conferring a higher transmission rate by the mosquito Aedes albopictus. Assumed to have occurred independently on at least four separate occasions, this evolutionary convergence was suspected to be responsible for CHIKV worldwide expansion. However, assumptions on CHIKV emergence were mainly based on viral genetic changes and the role of the mosquito population quasispecies remained unexplored. Here we show that the nature of the vector population is pivotal in selecting the epidemic CHIKV. We demonstrate using microsatellites mosquito genotyping that Ae. albopictus populations are genetically differentiated, contributing to explain their differential ability to select the E1-226V mutation. Aedes albopictus, newly introduced in Congo coinciding with the first CHIKV outbreak, was not able to select the substitution E1-A226V nor to preferentially transmit a CHIKV clone harboring the E1-226V as did Ae. albopictus from La Reunion. PMID- 27383737 TI - Molecular dyad approaches to the detection and photosensitization of singlet oxygen for biological applications. AB - The principles and prospects of a molecular dyad strategy for photocontrolling biological singlet oxygen are highlighted. PMID- 27383738 TI - Antibody complement-mediated hemolytic studies with kodecytes reveal that human complement utilized in the classical pathway is more stable than generally accepted. AB - BACKGROUND: Complement has significant status in the field of transfusion medicine. The accepted stability profile of complement is based on historical studies of diluted human serum hemolyzing rabbit heterophile antibody-sensitized sheep red blood cells (RBCs). Contemporary tools are available to reevaluate these historical observations using human heterophile antibodies, undiluted serum, and antigen-modified human RBCs. STUDY DESIGN AND METHODS: Human RBCs were made into "animal-like" kodecytes with heterophile Galalpha3Galbeta4GlcNAcbeta function-spacer-lipid constructs. These alpha-Gal-kodecytes were prepared with an antigen dilution capable of consistently producing 50% antibody-mediated hemolysis against human alpha1-3galactose heterophile antibodies and undiluted standardized serum. Standardized human serum aliquots from a two-donor pool stored at -85, -20, 4, 22, and 37 degrees C for durations of up to 150 days were evaluated for loss of hemolytic activity. Where practical methodologic procedures were aligned with historical studies. RESULTS: Comparison of the historical assay with the alpha-Gal-kodecyte assay against complement activity standards showed concordance. However, in most scenarios complement was found to be more than twice as stable as generally accepted. At least 60% of complement hemolytic activity was observed in serum stored at 22 degrees C for 1 week or 2 months at 4 degrees C. No loss of hemolytic activity was observed after 5 months' storage at temperatures below -20 degrees C. CONCLUSIONS: An alternative method using undiluted serum and modified human RBCs observed that classical-pathway complement hemolytic activity in stored human serum is at least twice as stable as previously accepted. PMID- 27383739 TI - High-Output-Power Ultraviolet Light Source from Quasi-2D GaN Quantum Structure. AB - Quasi-2D GaN layers inserted in an AlGaN matrix are proposed as a novel active region to develop a high-output-power UV light source. Such a structure is successfully achieved by precise control in molecular beam epitaxy and shows an amazing output power of ~160 mW at 285 nm with a pulsed electron-beam excitation. This device is promising and competitive in non-line-of-sight communications or the sterilization field. PMID- 27383740 TI - Reuse performance of granular-activated carbon and activated carbon fiber in catalyzed peroxymonosulfate oxidation. AB - Recently, activated carbon was investigated as an efficient heterogeneous metal free catalyst to directly activate peroxymonosulfate (PMS) for degradation of organic compounds. In this paper, the reuse performance and the possible deactivation reasons of granular-activated carbon (GAC) and activated carbon fiber (ACF) in PMS activation were investigated. As results indicated, the reusability of GAC, especially in the presence of high PMS dosage, was relatively superior to ACF in catalyzed PMS oxidation of Acid Orange 7 (AO7), which is much more easily adsorbed by ACF than by GAC. Pre-oxidation experiments were studied and it was demonstrated that PMS oxidation on ACF would retard ACF's deactivation to a big extent. After pre-adsorption with AO7, the catalytic ability of both GAC and ACF evidently diminished. However, when methanol was employed to extract the AO7-spent ACF, the catalytic ability could recover quite a bit. GAC and ACF could also effectively catalyze PMS to degrade Reactive Black 5 (RB5), which is very difficult to be adsorbed even by ACF, but both GAC and ACF have poor reuse performance for RB5 degradation. The original organic compounds or intermediate products adsorbed by GAC or ACF would be possibly responsible for the deactivation. PMID- 27383741 TI - Early-stage clear cell tubulopapillary renal cell carcinoma: imaging features and distinction from clear cell and papillary subtypes. AB - PURPOSE: Clear cell tubulopapillary renal cell carcinoma (CCTPRCC) is a recently described, low-grade subtype of renal cancer. We determined if imaging features could be used to distinguish early-stage CCTPRCC from stage-matched clear cell RCC (ccRCC) and papillary RCC (pRCC). METHODS: This IRB-approved retrospective study included 54 stage T1a patients with pathologically confirmed CCTPRCC (n = 18), ccRCC (n = 18), and pRCC (n = 18). CT (n = 48) and MRI (n = 27) exams were reviewed and imaging features compared. Continuous variables were evaluated using ANOVA and Tukey's multiple comparison tests. Categorical variables were compared using Chi-square test or Fisher's exact test. RESULTS: Compared to pRCC, CCTPRCC had a lower mean attenuation value on unenhanced CT (p < 0.017), was more often hyperintense on T2-weighted images (p < 0.0001), showed an ill-defined margin (p = 0.003), and demonstrated nonenhancing areas (p = 0.0003). The presence of all three of these statistically significant features [hypoattenuation (unenhanced attenuation <=25 HU), ill-defined margin, nonenhancing areas] yielded an area under the receiver operator curve (ROC) of 0.92 (95% CI 0.83-0.99) for differentiating CCTPRCC from pRCC. There were no significant differences in the imaging features of CCTPRCC and ccRCC. CONCLUSIONS: Early-stage clear cell tubulopapillary renal cell carcinoma can be distinguished from papillary RCC based on low attenuation on unenhanced CT, high intensity on T2-weighted images, an ill-defined margin, and presence of nonenhancing areas, but cannot be distinguished from clear cell RCC. PMID- 27383742 TI - Three subgroups of pain profiles identified in 227 women with arthritis: a latent class analysis. AB - The objectives were to identify subgroups of women with arthritis based upon the multi-dimensional nature of their pain experience and to compare health and socio demographic variables between subgroups. A latent class analysis of 227 women with self-reported arthritis was used to identify clusters of women based upon the sensory, affective, and cognitive dimensions of the pain experience. Multivariate multinomial logistic regression analysis was used to determine the relationship between cluster membership and health and sociodemographic characteristics. A three-class cluster model was most parsimonious. 39.5 % of women had a unidimensional pain profile; 38.6 % of women had moderate multidimensional pain profile that included additional pain symptomatology such as sensory qualities and pain catastrophizing; and 21.9 % of women had severe multidimensional pain profile that included prominent pain symptomatology such as sensory and affective qualities of pain, pain catastrophizing, and neuropathic pain. Women with severe multidimensional pain profile have a 30.5 % higher risk of poorer quality of life and a 7.3 % higher risk of suffering depression, and women with moderate multidimensional pain profile have a 6.4 % higher risk of poorer quality of life when compared to women with unidimensional pain. This study identified three distinct subgroups of pain profiles in older women with arthritis. Women had very different experiences of pain, and cluster membership impacted significantly on health-related quality of life. These preliminary findings provide a stronger understanding of profiles of pain and may contribute to the development of tailored treatment options in arthritis. PMID- 27383743 TI - An Evidence-Based Antimicrobial Stewardship Smartphone App for Hospital Outpatients: Survey-based Needs Assessment Among Patients. AB - BACKGROUND: Current advances in modern technology have enabled the development and utilization of electronic medical software apps for both mobile and desktop computing devices. A range of apps on a large variety of clinical conditions for patients and the public are available, but very few target antimicrobials or infections. OBJECTIVE: We sought to explore the use of different antimicrobial information resources with a focus on electronic platforms, including apps for portable devices, by outpatients at two large, geographically distinct National Health Service (NHS) teaching hospital trusts in England. We wanted to determine whether there is demand for an evidence-based app for patients, to garner their perceptions around infections/antimicrobial prescribing, and to describe patients' experiences of their interactions with health care professionals in relation to this topic. METHODS: A cross-sectional survey design was used to investigate aspects of antimicrobial prescribing and electronic devices experienced by patients at four hospitals in London and a teaching hospital in the East of England. RESULTS: A total of 99 surveys were completed and analyzed. A total of 82% (80/98) of respondents had recently been prescribed antimicrobials; 87% (85/98) of respondents were prescribed an antimicrobial by a hospital doctor or through their general practitioner (GP) in primary care. Respondents wanted information on the etiology (42/65, 65%) and prevention and/or management (32/65, 49%) of their infections, with the infections reported being upper and lower respiratory tract, urinary tract, oral, and skin and soft tissue infections. All patients (92/92, 100%) desired specific information on the antimicrobial prescribed. Approximately half (52/95, 55%) stated it was "fine" for doctors to use a mobile phone/tablet computer during the consultation while 13% (12/95) did not support the idea of doctors accessing health care information in this way. Although only 30% (27/89) of respondents reported on the use of health care apps, 95% (81/85) offered information regarding aspects of antimicrobials or infections that could be provided through a tailored app for patients. Analysis of the comments revealed the following main global themes: knowledge, technology, and patient experience. CONCLUSIONS: The majority of respondents in our study wanted to have specific etiological and/or infection management advice. All required antimicrobial-related information. Also, most supported the use of electronic resources of information, including apps, by their doctors. While a minority of people currently use health apps, many feel that apps could be used to provide additional support/information related to infections and appropriate use of antimicrobials. In addition, we found that there is a need for health care professionals to engage with patients and help address common misconceptions around the generation of antimicrobial resistance. PMID- 27383744 TI - Localised Effects of a Mega-Disturbance: Spatiotemporal Responses of Intertidal Sandy Shore Communities to the 2010 Chilean Earthquake. AB - Determining the effects of unpredictable disturbances on dynamic ecological systems is challenged by the paucity of appropriate temporal and spatial coverage of data. On 27 February 2010, an 8.8 Mw mega-earthquake and tsunami struck central Chile and caused coastal land-level changes, massive damage to coastal infrastructure, and widespread mortality of coastal organisms. Wave-exposed sandy beaches showed significant changes of species abundances from before to after the earthquake, but the highly dynamic biotic and abiotic conditions of these habitats make difficult to draw clear-cut conclusions from these patterns. Here, we analysed a beyond-BACI (Before-After Control-Impact) sampling design to test whether the effects of the Maule earthquake on sandy-shore species diversity, abundance, and structure were heterogeneous along the shore. Invertebrate species abundances were quantified before (i.e. February 2010) and after (i.e. March 2010, September 2010, and March 2011) the earthquake at three sandy shores randomly located within the earthquake rupture area and three sites within a "control" area located >400 km southward from epicentre. Immediately after the earthquake took place, the three sites located in the rupture area showed anomalous beach-profile uplifts that did not comply with the erosion (i.e. "negative" uplifts) that regularly occurs during late summer in the region. Species richness, abundance, and community structure significantly varied from before to after the strike, but these patterns of change varied among sites within both areas. Only the site with the strongest and persistent beach-profile uplift within the rupture area showed significant concomitant changes in species richness and community structure; after 13 months, this community showed a similar multivariate structure to the before-disturbance state. This site, in particular, was located in the section of the rupture area that received most of the impact of the after-earthquake tsunami. Therefore, our results suggest that the effects of the Maule mega-earthquake on the ecological communities were spatially heterogeneous and highly localised. We suggest that high mobility and other species' adaptations to the dynamic environmental conditions of sandy beaches might explain the comparatively high resilience of these assemblages. With this work we hope to motivate further experimental research on the role of individual- and population-level properties in the response of sandy-beach communities to interacting sources of disturbances. PMID- 27383745 TI - The perceived constraints subscale of the Sense of Mastery Scale: dimensionality and measurement invariance. AB - PURPOSE: A number of studies have reported differences in sense of mastery and perceived control across different subgroups. Yet, few have examined measurement invariance, an important prerequisite for valid comparisons. This study examines the factorial structure and measurement invariance of the perceived constraints (PC) facet of Pearlin and Schooler's (1981) Sense of Mastery Scale (SM) which is a commonly used short form of the widely used SM scale. METHODS: Confirmatory factor analyses using AMOS and Mplus were conducted to explore dimensionality and test for measurement invariance in factor structure, factor loadings, intercepts, and residual variances across gender, age, education, income, and employment status in a large (N = 19,858), nationally representative sample of Norwegian males and females aged 16-100. RESULTS: The data supported a modified unidimensional model specifying correlations between the error terms of items 4 and 5, or possibly two highly correlated dimensions (r = 0.90). Metric invariance of the scale was shown for age, education, and employment, whereas invariance at the strong and strict levels was shown for gender and income. Partial invariance at the strong level was shown for age. CONCLUSIONS: This Norwegian study supported a modified unidimensional structure for the abbreviated SM scale. Invariance testing indicated that comparisons across genders and income levels are unproblematic, whilst comparing mean scores across education and employment status is not justified. Latent, but not sum score means are comparable across age. Future studies using all 7 items of SM scale should provide more information on dimensionality and measurement invariance. PMID- 27383746 TI - Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum. AB - A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous) cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10), medium (n = 8), and high (n = 12) lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows. PMID- 27383748 TI - Initial founders of captive populations are genetically representative of natural populations in critically endangered dusky gopher frogs, Lithobates sevosus. AB - The rapid rate of decline in amphibian populations has urged many researchers and conservationists to establish captive, or ex situ, populations. Such populations are guarded against effects of habitat loss and degradation, and if actively managed, can serve as a reservoir for rare alleles that might be lost in the wild. Without proper management, ex situ population sizes can dwindle and will no longer perform this function. The dusky gopher frog, Lithobates sevosus, is a critically endangered species, imperiled by habitat loss and population isolation. To assist in recovery of the species and prevent further genetic erosion, a captive breeding program was initiated. We investigated how well natural genetic variation was captured within the ex situ population and determined relatedness within each ex situ population. We genotyped individuals from two natural populations and two founding, captive populations to compare metrics of genetic variation and relatedness. The data show the initial founder populations are genetically representative of the natural populations, although variation is low in each, and that relatedness values are similar. Therefore, founding captive populations were successful at capturing genetic variation in the wild. Future research should continue to compare genetic variation of captive and natural populations to monitor efficacy of their management programs. Zoo Biol. 35:378-384, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27383747 TI - In-situ coupling between kinase activities and protein dynamics within single focal adhesions. AB - The dynamic activation of oncogenic kinases and regulation of focal adhesions (FAs) are crucial molecular events modulating cell adhesion in cancer metastasis. However, it remains unclear how these events are temporally coordinated at single FA sites. Therefore, we targeted fluorescence resonance energy transfer (FRET) based biosensors toward subcellular FAs to report local molecular events during cancer cell adhesion. Employing single FA tracking and cross-correlation analysis, we quantified the dynamic coupling characteristics between biochemical kinase activities and structural FA within single FAs. We show that kinase activations and FA assembly are strongly and sequentially correlated, with the concurrent FA assembly and Src activation leading focal adhesion kinase (FAK) activation by 42.6 +/- 12.6 sec. Strikingly, the temporal coupling between kinase activation and individual FA assembly reflects the fate of FAs at later stages. The FAs with a tight coupling tend to grow and mature, while the less coupled FAs likely disassemble. During FA disassembly, however, kinase activations lead the disassembly, with FAK being activated earlier than Src. Therefore, by integrating subcellularly targeted FRET biosensors and computational analysis, our study reveals intricate interplays between Src and FAK in regulating the dynamic life of single FAs in cancer cells. PMID- 27383750 TI - Moved by words: Affective ratings for a set of 2,266 Spanish words in five discrete emotion categories. AB - The two main theoretical accounts of the human affective space are the dimensional perspective and the discrete-emotion approach. In recent years, several affective norms have been developed from a dimensional perspective, including ratings for valence and arousal. In contrast, the number of published datasets relying on the discrete-emotion approach is much lower. There is a need to fill this gap, considering that discrete emotions have an effect on word processing above and beyond those of valence and arousal. In the present study, we present ratings from 1,380 participants for a set of 2,266 Spanish words in five discrete emotion categories: happiness, anger, fear, disgust, and sadness. This will be the largest dataset published to date containing ratings for discrete emotions. We also present, for the first time, a fine-grained analysis of the distribution of words into the five emotion categories. This analysis reveals that happiness words are the most consistently related to a single, discrete emotion category. In contrast, there is a tendency for many negative words to belong to more than one discrete emotion. The only exception is disgust words, which overlap least with the other negative emotions. Normative valence and arousal data already exist for all of the words included in this corpus. Thus, the present database will allow researchers to design studies to contrast the predictions of the two most influential theoretical perspectives in this field. These studies will undoubtedly contribute to a deeper understanding of the effects of emotion on word processing. PMID- 27383751 TI - A study of artificial eyes for the measurement of precision in eye-trackers. AB - The precision of an eye-tracker is critical to the correct identification of eye movements and their properties. To measure a system's precision, artificial eyes (AEs) are often used, to exclude eye movements influencing the measurements. A possible issue, however, is that it is virtually impossible to construct AEs with sufficient complexity to fully represent the human eye. To examine the consequences of this limitation, we tested currently used AEs from three manufacturers of eye-trackers and compared them to a more complex model, using 12 commercial eye-trackers. Because precision can be measured in various ways, we compared different metrics in the spatial domain and analyzed the power-spectral densities in the frequency domain. To assess how precision measurements compare in artificial and human eyes, we also measured precision using human recordings on the same eye-trackers. Our results show that the modified eye model presented can cope with all eye-trackers tested and acts as a promising candidate for further development of a set of AEs with varying pupil size and pupil-iris contrast. The spectral analysis of both the AE and human data revealed that human eye data have different frequencies that likely reflect the physiological characteristics of human eye movements. We also report the effects of sample selection methods for precision calculations. This study is part of the EMRA/COGAIN Eye Data Quality Standardization Project. PMID- 27383752 TI - A computational modeling of semantic knowledge in reading comprehension: Integrating the landscape model with latent semantic analysis. AB - It is a well-accepted view that the prior semantic (general) knowledge that readers possess plays a central role in reading comprehension. Nevertheless, computational models of reading comprehension have not integrated the simulation of semantic knowledge and online comprehension processes under a unified mathematical algorithm. The present article introduces a computational model that integrates the landscape model of comprehension processes with latent semantic analysis representation of semantic knowledge. In three sets of simulations of previous behavioral findings, the integrated model successfully simulated the activation and attenuation of predictive and bridging inferences during reading, as well as centrality estimations and recall of textual information after reading. Analyses of the computational results revealed new theoretical insights regarding the underlying mechanisms of the various comprehension phenomena. PMID- 27383749 TI - Transcriptome Analysis of the Innate Immunity-Related Complement System in Spleen Tissue of Ctenopharyngodon idella Infected with Aeromonas hydrophila. AB - The grass carp (Ctenopharyngodon idella) is an important commercial farmed herbivorous fish species in China, but is susceptible to Aeromonas hydrophila infections. In the present study, we performed de novo RNA-Seq sequencing of spleen tissue from specimens of a disease-resistant family, which were given intra-peritoneal injections containing PBS with or without a dose of A. hydrophila. The fish were sampled from the control group at 0 h, and from the experimental group at 4, 8, 12, 24, 48 and 72 h. 122.18 million clean reads were obtained from the normalized cDNA libraries; these were assembled into 425,260 contigs and then 191,795 transcripts. Of those, 52,668 transcripts were annotated with the NCBI Nr database, and 41,347 of the annotated transcripts were assigned into 90 functional groups. 20,569 unigenes were classified into six main categories, including 38 secondary KEGG pathways. 2,992 unigenes were used in the analysis of differentially expressed genes (DEGs). 89 of the putative DEGs were related to the immune system and 41 of them were involved in the complement and coagulation cascades pathway. This study provides insights into the complement and complement-related pathways involved in innate immunity, through expression profile analysis of the genomic resources in C. idella. We conclude that complement and complement-related genes play important roles during defense against A. hydrophila infection. The immune response is activated at 4 h after the bacterial injections, indicating that the complement pathways are activated at the early stage of bacterial infection. The study has improved our understanding of the immune response mechanisms in C. idella to bacterial pathogens. PMID- 27383753 TI - Detecting correlation changes in multivariate time series: A comparison of four non-parametric change point detection methods. AB - Change point detection in multivariate time series is a complex task since next to the mean, the correlation structure of the monitored variables may also alter when change occurs. DeCon was recently developed to detect such changes in mean and?or correlation by combining a moving windows approach and robust PCA. However, in the literature, several other methods have been proposed that employ other non-parametric tools: E-divisive, Multirank, and KCP. Since these methods use different statistical approaches, two issues need to be tackled. First, applied researchers may find it hard to appraise the differences between the methods. Second, a direct comparison of the relative performance of all these methods for capturing change points signaling correlation changes is still lacking. Therefore, we present the basic principles behind DeCon, E-divisive, Multirank, and KCP and the corresponding algorithms, to make them more accessible to readers. We further compared their performance through extensive simulations using the settings of Bulteel et al. (Biological Psychology, 98 (1), 29-42, 2014) implying changes in mean and in correlation structure and those of Matteson and James (Journal of the American Statistical Association, 109 (505), 334-345, 2014) implying different numbers of (noise) variables. KCP emerged as the best method in almost all settings. However, in case of more than two noise variables, only DeCon performed adequately in detecting correlation changes. PMID- 27383754 TI - Individual classification of elementary school children's physical activity: A time-efficient, group-based approach to reference measurements. AB - The objective measurement of physical activity using accelerometers is becoming increasingly popular. There is little consensus, however, about how to analyze acceleration data. One promising approach is the use of reference measurements in which the subjects conduct specific activities. This makes it possible to identify data patterns that indicate these activities for each subject. The drawback of this approach is its rather high cost, in terms of both time and money. We propose a new approach in which a group of children conduct the reference measurements at the same time. We trained support vector machine models on the accelerometer data of 70 children (ages 8-11 years) to predict their activities during those reference measurements. We correctly classified activities with an accuracy of 96.9 % when fitting the individual models for each subject, and 87.5 % when fitting general models for all subjects. The obtained accuracies were comparable to results reported in previous reference measurement studies, in which each subject was measured individually. They were higher than the accuracies obtained by the traditional approach, which transfers accelerometer data to counts and classifies those on the basis of predefined cut points. We concluded that our approach can yield a valuable contribution, particularly to studies with larger samples. PMID- 27383755 TI - CBT profiles of cabozantinib approved for advanced renal cell carcinomas. PMID- 27383756 TI - Motion-insensitive carotid intraplaque hemorrhage imaging using 3D inversion recovery preparation stack of stars (IR-prep SOS) technique. AB - PURPOSE: Carotid artery imaging is important in the clinical management of patients at risk for stroke. Carotid intraplaque hemorrhage (IPH) presents an important diagnostic challenge. 3D magnetization prepared rapid acquisition gradient echo (MPRAGE) has been shown to accurately image carotid IPH; however, this sequence can be limited due to motion- and flow-related artifact. The purpose of this work was to develop and evaluate an improved 3D carotid MPRAGE sequence for IPH detection. We hypothesized that a radial-based k-space trajectory sequence such as "Stack of Stars" (SOS) incorporated with inversion recovery preparation would offer reduced motion sensitivity and more robust flow suppression by oversampling of central k-space. MATERIALS AND METHODS: A total of 31 patients with carotid disease (62 carotid arteries) were imaged at 3T magnetic resonance imaging (MRI) with 3D IR-prep Cartesian and SOS sequences. Image quality was determined between SOS and Cartesian MPRAGE in 62 carotid arteries using t-tests and multivariable linear regression. Kappa analysis was used to determine interrater reliability. RESULTS: In all, 25 among 62 carotid plaques had carotid IPH by consensus from the reviewers on SOS compared to 24 on Cartesian sequence. Image quality was significantly higher with SOS compared to Cartesian (mean 3.74 vs. 3.11, P < 0.001). SOS acquisition yielded sharper image features with less motion (19.4% vs. 45.2%, P < 0.002) and flow artifact (27.4% vs. 41.9%, P < 0.089). There was also excellent interrater reliability with SOS (kappa = 0.89), higher than that of Cartesian (kappa = 0.84). CONCLUSION: By minimizing flow and motion artifacts and retaining high interrater reliability, the SOS MPRAGE has important advantages over Cartesian MPRAGE in carotid IPH detection. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:410-417. PMID- 27383758 TI - Assessment and management of cirrhosis in people older than 16 years: summary of NICE guidance. PMID- 27383757 TI - The influence of oxidative stress and autophagy cross regulation on pregnancy outcome. AB - The generation of reactive oxygen species (ROS), a byproduct of aerobic energy metabolism, is maintained at physiological levels by the activity of antioxidant components. Insufficiently opposed ROS results in oxidative stress characterized by altered mitochondrial function, decreased protein activity, damage to nucleic acids, and induction of apoptosis. Elevated levels of inadequately opposed ROS induce autophagy, a major intracellular pathway that sequesters and removes damaged macromolecules and organelles. In early pregnancy, autophagy induction preserves trophoblast function in the low oxygen and nutrient placental environment. Inadequate regulation of the ROS-autophagy axis leads to abnormal autophagy activity and contributes to the development of preeclampsia and intrauterine growth restriction. ROS-autophagy interactions are altered at the end of gestation and participate in the initiation of parturition at term. The induction of high levels of ROS coupled with a failure to induce a corresponding increase in autophagy results in the triggering of preterm labor and delivery. PMID- 27383760 TI - Teenage intimate partner violence: Factors associated with victimization among Norwegian youths. AB - OBJECTIVE: The aim of the present study was threefold: (1) learn more about factors associated with teenage intimate partner violence (IPV) victimization; (2) explore aspects of digital media use in connection with teenage IPV; (3) and compare the impact IPV victimization has on boys and girls. METHOD: Survey data from 549 Norwegian students, mean age 15.2 years, who had experience(s) with being in intimate relationship(s), were examined. Experiences with psychological, physical, digital, and sexual violence were analyzed. RESULTS: In total, 42.9% of the participants had experienced some form of IPV: 29.1% had experienced digital violence; 25.9% had experienced psychological violence; 18.8% had experienced sexual violence; and 12.8% had experienced physical violence. Factors significantly associated with teenage IPV victimization were female gender, older partners, domestic violence, bullying victimization, low academic achievements, and sending sexual messages via digital media. Girls reported to be significantly more negatively impacted by the victimization than boys. CONCLUSIONS: Some teenagers experience victimization in their intimate relationships, and for many digital media seems to play a central role in this violence. Teenagers who experience victimization outside their relationships or have risky lifestyles have a higher risk of experiencing IPV victimization. A focus on teenage IPV, and especially digital media's role in this violence, is needed if this public health issue is to be combated. PMID- 27383759 TI - Soluble calcium-binding proteins (SCBPs) of the earthworm Lumbricus terrestris: molecular characterization and localization by FISH in muscle and neuronal tissue. AB - Soluble calcium-binding proteins (SCBPs) of invertebrates probably serve like their vertebrate counterpart-the parvalbumins-as soluble relaxing factors in muscles. Three SCBP isoforms (SCBP1-3) have been isolated and biochemically characterized in the earthworm Lumbricus terrestris (Huch et al. in J Comp Physiol B 158:325-334, 1988). For SCBP2, we found two isoforms named SCBP2a/2b. Both of them together with SCBP3 are present in the body wall muscle. In the gizzard solely, SCBP2b and no SCBP2a or SCBP3 could be detected. The coding sequences of all three isoforms consist of 534 bp for 178 amino acids and contain four EF-hand motifs, of which the second EF-hands are truncated. Recombinant proteins show heat stability and a Ca2+-dependent mobility shift similar to the native proteins, indicating comparable calcium-binding properties. All three isoforms are encoded by three distinct and differentially expressed genes. The genes for SCBP2a, SCBP2b, and SCBP3 are interrupted by only one intron, inserting at nearly the same positions. Northern blot analysis revealed two mRNA transcripts for SCBP2 of approximately 1250 and 1500 kb and one transcript for SCBP3 of approximately 1250 kb. SCBP mRNA was localized by fluorescent in situ hybridization in the body wall and the gizzard. The distribution of the staining intensities resembles that for the myosin ATPase activity and indicates a correlation between the amount of SCBP and speed of muscle contraction. In addition, SCBP mRNA was localized within the nervous tissue, the cerebral and subesophageal ganglia and the ventral nerve cord. PMID- 27383761 TI - Identification of Phosphorylated Cyclin-Dependent Kinase 1 Associated with Colorectal Cancer Survival Using Label-Free Quantitative Analyses. AB - Colorectal cancer is the most common form of cancer in the world, and the five year survival rate is estimated to be almost 90% in the early stages. Therefore, the identification of potential biomarkers to assess the prognosis of early stage colorectal cancer patients is critical for further clinical treatment. Dysregulated tyrosine phosphorylation has been found in several diseases that play a significant regulator of signaling in cellular pathways. In this study, this strategy was used to characterize the tyrosine phosphoproteome of colorectal cell lines with different progression abilities (SW480 and SW620). We identified a total of 280 phosphotyrosine (pTyr) peptides comprising 287 pTyr sites from 261 proteins. Label-free quantitative analysis revealed the differential level of a total of 103 pTyr peptides between SW480 and SW620 cells. We showed that cyclin dependent kinase I (CDK1) pTyr15 level in SW480 cells was 3.3-fold greater than in SW620 cells, and these data corresponded with the label-free mass spectrometry based proteomic quantification analysis. High level CDK1 pTyr15 was associated with prolonged disease-free survival for stage II colorectal cancer patients (n = 79). Taken together, our results suggest that the CDK1 pTyr15 protein is a potential indicator of the progression of colorectal cancer. PMID- 27383762 TI - Evaluation of the effects of olodaterol on exercise endurance in patients with chronic obstructive pulmonary disease: results from two 6-week crossover studies. AB - BACKGROUND: Two replicate, double-blind, placebo-controlled, 6-week crossover studies assessed the effect of the once-daily long-acting beta2-agonist olodaterol 5 MUg and 10 MUg on constant work-rate cycle endurance in patients with moderate to very severe chronic obstructive pulmonary disease. METHODS: Patients received placebo, olodaterol 5 MUg once daily (QD) and olodaterol 10 MUg QD in a randomised order for 6 weeks each, with a 2-week washout period in between. The primary end point was change in endurance time during constant work rate cycle ergometry to symptom limitation at 75 % maximal work capacity after 6 weeks of treatment (2 h post-dose), based on log10-transformed data. Key secondary end points were inspiratory capacity at isotime and intensity of breathing discomfort at isotime. RESULTS: 151 and 157 patients were randomised and treated in Studies 1222.37 and 1222.38, respectively, with 147 and 154 being included in the full analysis sets. Mean endurance time at week 6 was increased compared to placebo by 14.0 % (Study 1222.37; p < 0.001) and 11.8 % (Study 1222.38; p < 0.01) with olodaterol 5 MUg, and by 13.8 % (Study 1222.37; p < 0.001) and 10.5 % (Study 1222.38; p < 0.01) with olodaterol 10 MUg. Inspiratory capacity at isotime increased with olodaterol 5 MUg (Study 1222.37, 0.182 L, p < 0.0001; Study 1222.38, 0.084 L, p < 0.05) and 10 MUg (Study 1222.37, 0.174 L; Study 1222.38, 0.166 L; both studies, p < 0.0001), and breathing discomfort was significantly reduced in Study 1222.37 (olodaterol 5 MUg, 0.77 Borg units, p < 0.001; olodaterol 10 MUg, 0.63 Borg units, p < 0.01) but not Study 1222.38. CONCLUSIONS: These studies provide further characterisation of the efficacy of olodaterol, showing that improvements in airflow (forced expiratory volume in 1 s) are associated with increases in inspiratory capacity and improvements in exercise endurance time. TRIAL REGISTRATIONS: NCT01040130 (1222.37) and NCT01040793 (1222.38). PMID- 27383763 TI - Quantitative gait analysis in parkin disease: Possible role of dystonia. AB - INTRODUCTION: Parkin disease (PARK2, OMIM 602544) is an autosomal-recessive early onset parkinsonism characterized by an early occurrence of lower limb dystonia. The aim of this study was to analyze spatiotemporal, kinematic, and kinetic gait parameters in patients with parkin disease in the OFF and ON conditions compared to healthy age-matched controls. METHODS: Fifteen patients with parkin disease and 15 healthy age-matched controls were studied in a gait analysis laboratory with an integrated optoelectronic system. Spatiotemporal, kinematic, and kinetic gait parameters at a self-selected speed were recorded in the OFF and ON conditions. A jerk index was computed to quantify the possible reduction of smoothness of joint movements. RESULTS: Compared to controls, parkin patients had, either in the OFF or in the ON conditions, significant reduction of walking velocity, increased step width, and decreased percentage of double support. Kinematic analysis in both conditions showed: increased ankle dorsiflexion and knee flexion at the initial contact; maximal flexion and increased range of motion in mid stance; increased hip flexion and max extension in stance at pelvis; and increased mean tilt antiversion. Kinetics showed increased hip and knee power generation in stance in either condition. The jerk index was increased at all joints both in OFF and ON. There were no correlations between individual gait parameters and clinical ratings. CONCLUSION: Parkin patients have an abnormal gait pattern that does not vary between the OFF and the ON conditions. Variations recorded with instrumented analysis are more evident for kinematic than kinetic parameters at lower limbs. Severity of dystonia does not correlate with any individual kinematic parameter. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27383764 TI - Prognostic Significance of Monocytes and Monocytic Myeloid-Derived Suppressor Cells in Diffuse Large B-Cell Lymphoma Treated with R-CHOP. AB - BACKGROUND/AIMS: To evaluate the prognostic significance of monocytes and monocytic myeloid-derived suppressor cells (M-MDSCs) for patients with diffuse large B-cell lymphoma (DLBCL) under R-CHOP chemotherapy. METHODS: Flow cytometry (FCM) was applied to measure M-MDSCs (CD14+ HLA-DRlow/- M-MDSCs). RESULTS: Analysis of 144 patients with DLBCL under R-CHOP treatment showed that the 5-year overall survival rate was 61.09% (95% CI: 43.72%-72.56%) and the average survival time of patients with monocytes (%) >= 8% was shorter than those with monocytes (%) < 8% (P = 0.0036). Further stratified analysis suggested that the average survival time of patients with monocytes (%) >= 8% was shorter than patients with monocytes (%) < 8% in the moderate outcome group (R-IPI = 1, 2) (P = 0.0168) and in the poorest outcome group (R-IPI > 2) (P = 0.0397), meanwhile, there was no significant difference in survival of patients with monocytes (%) >= 8% compared to patients with monocytes (%) < 8% in the best outcome group (R-IPI = 0) (P = 0.3106). Both of monocytes (%) and M-MDSCs were decreased in different R-IPI groups after 4-course of R-CHOP chemotherapy (P < 0.05). CONCLUSION: Our results indicated that monocytes (%) and M-MDSCs combined with R-IPI may be a simple and efficient immunological index to evaluate prognosis. PMID- 27383766 TI - Enantioselective Rhodium-Catalyzed Atom-Economical Macrolactonization. AB - A highly attractive route toward macrolactones, which form the cyclic scaffold of a multitude of diverse natural compounds, is described. Although many chemical approaches to this structural motif have been explored, an asymmetric variant of the cyclization is unprecedented. Herein we present an enantioselective macrolactonization through an intramolecular atom-economical rhodium-catalyzed coupling of omega-allenyl-substituted carboxylic acids. The use of a modified diop ligand, chiral DTBM-diop, led to high enantioselectivity (up to 93 % ee). The reaction tolerated a large variety of functionalities, including alpha,beta unsaturated carboxylic acids and depsipeptides, and provided the desired macrocycles with very high enantio- and diastereoselectivity. PMID- 27383765 TI - Intrinsic Tau Acetylation Is Coupled to Auto-Proteolytic Tau Fragmentation. AB - Tau proteins are abnormally aggregated in a range of neurodegenerative tauopathies including Alzheimer's disease (AD). Recently, tau has emerged as an extensively post-translationally modified protein, among which lysine acetylation is critical for normal tau function and its pathological aggregation. Here, we demonstrate that tau isoforms have different propensities to undergo lysine acetylation, with auto-acetylation occurring more prominently within the lysine rich microtubule-binding repeats. Unexpectedly, we identified a unique intrinsic property of tau in which auto-acetylation induces proteolytic tau cleavage, thereby generating distinct N- and C-terminal tau fragments. Supporting a catalytic reaction-based mechanism, mapping and mutagenesis studies showed that tau cysteines, which are required for acetyl group transfer, are also essential for auto-proteolytic tau processing. Further mass spectrometry analysis identified the C-terminal 2nd and 4th microtubule binding repeats as potential sites of auto-cleavage. The identification of acetylation-mediated auto proteolysis provides a new biochemical mechanism for tau self-regulation and warrants further investigation into whether auto-catalytic functions of tau are implicated in AD and other tauopathies. PMID- 27383767 TI - Vertically aligned CNT-Cu nano-composite material for stacked through-silicon-via interconnects. AB - For future miniaturization of electronic systems using 3D chip stacking, new fine pitch materials for through-silicon-via (TSV) applications are likely required. In this paper, we propose a novel carbon nanotube (CNT)/copper nanocomposite material consisting of high aspect ratio, vertically aligned CNT bundles coated with copper. These bundles, consisting of hundreds of tiny CNTs, were uniformly coated by copper through electroplating, and aspect ratios as high as 300:1 were obtained. The resistivity of this nanomaterial was found to be as low as ~10(-8) Omega m, which is of the same order of magnitude as the resistivity of copper, and its temperature coefficient was found to be only half of that of pure copper. The main advantage of the composite TSV nanomaterial is that its coefficient of thermal expansion (CTE) is similar to that of silicon, a key reliability factor. A finite element model was set up to demonstrate the reliability of this composite material and thermal cycle simulations predicted very promising results. In conclusion, this composite nanomaterial appears to be a very promising material for future 3D TSV applications offering both a low resistivity and a low CTE similar to that of silicon. PMID- 27383768 TI - A balanced pyrimidine pool is required for optimal Chk1 activation to prevent ultrafine anaphase bridge formation. AB - Cytidine deaminase (CDA) deficiency induces an excess of cellular dCTP, which reduces basal PARP-1 activity, thereby compromising complete DNA replication, leading to ultrafine anaphase bridge (UFB) formation. CDA dysfunction has pathological implications, notably in cancer and in Bloom syndrome. It remains unknown how reduced levels of PARP-1 activity and pyrimidine pool imbalance lead to the accumulation of unreplicated DNA during mitosis. We report that a decrease in PARP-1 activity in CDA-deficient cells impairs DNA-damage-induced Chk1 activation, and, thus, the downstream checkpoints. Chemical inhibition of the ATR Chk1 pathway leads to UFB accumulation, and we found that this pathway was compromised in CDA-deficient cells. Our data demonstrate that ATR-Chk1 acts downstream from PARP-1, preventing the accumulation of unreplicated DNA in mitosis, and, thus, UFB formation. Finally, delaying entry into mitosis is sufficient to prevent UFB formation in both CDA-deficient and CDA-proficient cells, suggesting that both physiological and pathological UFBs are derived from unreplicated DNA. Our findings demonstrate an unsuspected requirement for a balanced nucleotide pool for optimal Chk1 activation both in unchallenged cells and in response to genotoxic stress. PMID- 27383769 TI - The RNA-binding protein Puf1 functions in the maintenance of gametocytes in Plasmodium falciparum. AB - Translation control plays an important role in the regulation of gene expression in the malaria parasite Plasmodium falciparum, especially in transition stages between the vertebrate host and mosquito vector. Here, we determined the function of the Puf-family member Puf1 (denoted as PfPuf1 for the P. falciparum protein) during P. falciparum sexual development. We show that PfPuf1 was expressed in all gametocyte stages and at higher levels in female gametocytes. PfPuf1 disruption did not interfere with the asexual erythrocyte cycle of the parasite but resulted in an approximately tenfold decrease of mature gametocytes. In the PfPuf1 disrupted lines, gametocytes appeared normal before stage III but subsequently exhibited a sharp decline in gametocytemia. This was accompanied by a concomitant accumulation of dead and dying late-stage gametocytes, which retained normal gross morphology. In addition, significantly more female gametocytes were lost in the PfPuf1-disrupted lines during development, resulting in a reversed male-to female sex ratio. These results indicate that PfPuf1 is important for the differentiation and maintenance of gametocytes, especially female gametocytes. PMID- 27383770 TI - Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice. AB - The neuroprotective role of carbon monoxide (CO) has been studied in a cell autonomous mode. Herein, a new concept is disclosed - CO affects astrocyte-neuron communication in a paracrine manner to promote neuroprotection. Neuronal survival was assessed when co-cultured with astrocytes that had been pre-treated or not with CO. The CO-pre-treated astrocytes reduced neuronal cell death, and the cellular mechanisms were investigated, focusing on purinergic signaling. CO modulates astrocytic metabolism and extracellular ATP content in the co-culture medium. Moreover, several antagonists of P1 adenosine and P2 ATP receptors partially reverted CO-induced neuroprotection through astrocytes. Likewise, knocking down expression of the neuronal P1 adenosine receptor A2A-R (encoded by Adora2a) reverted the neuroprotective effects of CO-exposed astrocytes. The neuroprotection of CO-treated astrocytes also decreased following prevention of ATP or adenosine release from astrocytic cells and inhibition of extracellular ATP metabolism into adenosine. Finally, the neuronal downstream event involves TrkB (also known as NTRK2) receptors and BDNF. Pharmacological and genetic inhibition of TrkB receptors reverts neuroprotection triggered by CO-treated astrocytes. Furthermore, the neuronal ratio of BDNF to pro-BDNF increased in the presence of CO-treated astrocytes and decreased whenever A2A-R expression was silenced. In summary, CO prevents neuronal cell death in a paracrine manner by targeting astrocytic metabolism through purinergic signaling. PMID- 27383771 TI - The Early Mother-to-Child Bond and Its Unique Prospective Contribution to Child Behavior Evaluated by Mothers and Teachers. AB - Maternal bonding has been described as the quality of the affective tie from a mother to her infant. This early bond's mental components and its longitudinal impact on child outcome have been markedly understudied. Although most researchers assume impaired maternal bonding to have a negative impact on child development, there is a lack of prospective studies evaluating this hypothesis. Since maternal mental health problems may negatively affect both bonding quality and child development, it is still to be determined whether there is a unique contribution of bonding quality to child behavior problems over and above maternal psychopathology. We examined a community sample of 101 mother-child dyads at the child's age of 2 weeks (t1) and 6 weeks (t2), 4 months (t3), 14 months (t4), and 5.5 years (t5). Maternal bonding and psychopathology were assessed at time points t1-t4 using the Postpartum Bonding Questionnaire (PBQ-16) and the Symptom Checklist Revised (SCL 90-R). Child behavior problems were rated in a multi-informant design by mothers and teachers at t5 using the Strengths and Difficulties Questionnaire (SDQ). In the case of maternal judgment of child behavior problems, bonding at 14 months (t4) proved to be a significant predictor (beta = 0.30; p = 0.011). Teacher-rated child behavior problems were significantly predicted by maternal bonding at 2 weeks (t1; beta = 0.48; p = 0.025). Our results indicate a prospective influence of the early mother-infant bond on child development and underline the unique contribution of bonding quality to child behavior problems over and above the impact of maternal psychopathology in a community sample. PMID- 27383772 TI - Pediatric death after unintentional exposure to liquid nicotine for an electronic cigarette. PMID- 27383773 TI - A Nomogram Derived by Combination of Demographic and Biomarker Data Improves the Noninvasive Evaluation of Patients at Risk for Bladder Cancer. AB - BACKGROUND: Improvements in the noninvasive clinical evaluation of patients at risk for bladder cancer would be of benefit both to individuals and to health care systems. We investigated the potential utility of a hybrid nomogram that combined key demographic features with the results of a multiplex urinary biomarker assay in hopes of identifying patients at risk of harboring bladder cancer. METHODS: Logistic regression analysis was used to model the probability of bladder cancer burden in a cohort of 686 subjects (394 with bladder cancer) using key demographic features alone, biomarker data alone, and the combination of demographic features and key biomarker data. We examined discrimination, calibration, and decision curve analysis techniques to evaluate prediction model performance. RESULTS: Area under the receiver operating characteristic curve (AUC) analyses revealed that demographic features alone predicted tumor burden with an accuracy of 0.806 [95% confidence interval (CI), 0.76-0.85], while biomarker data had an accuracy of 0.835 (95% CI, 0.80-0.87). The addition of molecular data into the nomogram improved the predictive performance to 0.891 (95% CI, 0.86-0.92). Decision curve analyses showed that the hybrid nomogram performed better than demographic or biomarker data alone. CONCLUSION: A nomogram construction strategy that combines key demographic features with biomarker data may facilitate the accurate, noninvasive evaluation of patients at risk of harboring bladder cancer. Further research is needed to evaluate the bladder cancer risk nomogram for potential clinical utility. IMPACT: The application of such a nomogram may better inform the decision to perform invasive diagnostic procedures. Cancer Epidemiol Biomarkers Prev; 25(9); 1361-6. (c)2016 AACR. PMID- 27383775 TI - Sexual Health Knowledge, Self-Efficacy and Behavioral Intentions Following a Health Fair for Adolescents. AB - High rates of human immunodeficiency virus (HIV) exist among urban African American youth. There is a need to provide HIV information to youth prior to the onset of sexual activity. The Stomping Out HIV intervention combines a health fair and step show to increase awareness and healthy behaviors among this population. Questionnaires were administered to youth and parents before and after Stomping Out, and focused on health knowledge, satisfaction with Stomping Out, intended behavior changes and self-efficacy to make healthier choices related to HIV and STI prevention. Youth and adults reported increased knowledge and self-efficacy after Stomping Out. These findings suggest that health initiatives focusing on sociocultural issues can greatly impact adults and youth. PMID- 27383774 TI - Risk of Lung Cancer Associated with COPD Phenotype Based on Quantitative Image Analysis. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a risk factor for lung cancer. This study evaluates alternative measures of COPD based on spirometry and quantitative image analysis to better define a phenotype that predicts lung cancer risk. METHODS: A total of 341 lung cancer cases and 752 volunteer controls, ages 21 to 89 years, participated in a structured interview, standardized CT scan, and spirometry. Logistic regression, adjusted for age, race, gender, pack-years, and inspiratory and expiratory total lung volume, was used to estimate the odds of lung cancer associated with FEV1/FVC, percent voxels less than -950 Hounsfield units on the inspiratory scan (HUI) and percent voxels less than -856 HU on expiratory scan (HUE). RESULTS: The odds of lung cancer were increased 1.4- to 3.1-fold among those with COPD compared with those without, regardless of assessment method; however, in multivariable modeling, only percent voxels <-856 HUE as a continuous measure of air trapping [OR = 1.04; 95% confidence interval (CI), 1.03-1.06] and FEV1/FVC < 0.70 (OR = 1.71; 95% CI, 1.21 2.41) were independent predictors of lung cancer risk. Nearly 10% of lung cancer cases were negative on all objective measures of COPD. CONCLUSION: Measures of air trapping using quantitative imaging, in addition to FEV1/FVC, can identify individuals at high risk of lung cancer and should be considered as supplementary measures at the time of screening for lung cancer. IMPACT: Quantitative measures of air trapping based on imaging provide additional information for the identification of high-risk groups who might benefit the most from lung cancer screening. Cancer Epidemiol Biomarkers Prev; 25(9); 1341-7. (c)2016 AACR. PMID- 27383776 TI - Nursing Student Birth Doulas' Influence On the Childbearing Outcomes of Vulnerable Populations. AB - Of 1,511 women served by nursing student birth doulas (Birth Companions) between 1998 and 2014, 34.5% were identified as vulnerable (refugees, non-English speakers, teens, low income, low education). This retrospective evaluation of the Birth Companions Program showed that vulnerable mothers had more epidurals and smaller babies, and attempted breastfeeding less frequently than nonvulnerable. There was no difference in the frequency of caesarean births, pitocin induction/augmentation, low birth weight, or preterm newborns among the vulnerable women. Birth Companion interventions may have a role in influencing these outcomes. The Birth Companions program will use this analysis to identify additional services for these populations. PMID- 27383777 TI - Enhancing Student Nurse Learning through Participation in a Community-Based Educational Program for Children and Families. AB - Health disparities, especially among minorities, persist; obesity is a national concern; and the combined effect can be significant for families and populations. In an effort to address obesity at an early age, the National Association of Hispanic Nurses (NAHN), developed the Muevete USATM project. Muevete USATM (from the Spanish verb for "to move") features five lesson plans on healthy lifestyles for children and their families. This article describes Muevete USATM, the partnership with a local school of nursing, the implementation of the program at the local level and the emerging program and student outcomes of a successful partnership. PMID- 27383778 TI - NAP SACC: Implementation of an Obesity Prevention Intervention in an American Indian Head Start Program. AB - Low-income American Indian preschoolers are at greatest risk for overweight and obesity among children aged 2-5 years. The Nutrition and Physical Activity Self Assessment for Child Care (NAP SACC) program is an evidence-based intervention that promotes healthy weight development for children enrolled in child care centers. The goal of this continuous quality improvement program is for the child care staff to establish environmental policies and practices that positively influence nutrition and physical activity-related behaviors. A community needs assessment of a Head Start program on an American Indian reservation identified obesity as a priority issue. This project implemented NAP SACC at 15 Head Start sites on the reservation. PMID- 27383779 TI - Effects of a South Korean Community-Based Cardiovascular Disease Prevention Program for Low-Income Elderly with Hypertension. AB - This study identified the effects of a community-based cardiovascular disease prevention program (CVD-PP) on health behavior and modifiable cardiovascular risk factors in low-income Korean elderly with hypertension. Eighty-eight individuals completed the 3-month self-efficacy-enhancing interventions in which the control group received standard care. In the intervention group, there were statistically significant improvements in self-efficacy (t = 2.519, p = 0.016) and health behavior (t = 3.453, p = 0.001), and significant differences in diastolic blood pressure (t = -2.518, p = 0.018) between the two groups. This CVD-PP administered by visiting nurses may be effective in improving self-efficacy and health behavior and in reducing modifiable cardiovascular risk factors. PMID- 27383782 TI - Molecular biology: A surprise beginning for RNA. PMID- 27383783 TI - High-efficiency two-dimensional Ruddlesden-Popper perovskite solar cells. AB - Three-dimensional organic-inorganic perovskites have emerged as one of the most promising thin-film solar cell materials owing to their remarkable photophysical properties, which have led to power conversion efficiencies exceeding 20 per cent, with the prospect of further improvements towards the Shockley-Queisser limit for a single-junction solar cell (33.5 per cent). Besides efficiency, another critical factor for photovoltaics and other optoelectronic applications is environmental stability and photostability under operating conditions. In contrast to their three-dimensional counterparts, Ruddlesden-Popper phases- layered two-dimensional perovskite films--have shown promising stability, but poor efficiency at only 4.73 per cent. This relatively poor efficiency is attributed to the inhibition of out-of-plane charge transport by the organic cations, which act like insulating spacing layers between the conducting inorganic slabs. Here we overcome this issue in layered perovskites by producing thin films of near-single-crystalline quality, in which the crystallographic planes of the inorganic perovskite component have a strongly preferential out-of plane alignment with respect to the contacts in planar solar cells to facilitate efficient charge transport. We report a photovoltaic efficiency of 12.52 per cent with no hysteresis, and the devices exhibit greatly improved stability in comparison to their three-dimensional counterparts when subjected to light, humidity and heat stress tests. Unencapsulated two-dimensional perovskite devices retain over 60 per cent of their efficiency for over 2,250 hours under constant, standard (AM1.5G) illumination, and exhibit greater tolerance to 65 per cent relative humidity than do three-dimensional equivalents. When the devices are encapsulated, the layered devices do not show any degradation under constant AM1.5G illumination or humidity. We anticipate that these results will lead to the growth of single-crystalline, solution-processed, layered, hybrid, perovskite thin films, which are essential for high-performance opto-electronic devices with technologically relevant long-term stability. PMID- 27383781 TI - Resolving early mesoderm diversification through single-cell expression profiling. AB - In mammals, specification of the three major germ layers occurs during gastrulation, when cells ingressing through the primitive streak differentiate into the precursor cells of major organ systems. However, the molecular mechanisms underlying this process remain unclear, as numbers of gastrulating cells are very limited. In the mouse embryo at embryonic day 6.5, cells located at the junction between the extra-embryonic region and the epiblast on the posterior side of the embryo undergo an epithelial-to-mesenchymal transition and ingress through the primitive streak. Subsequently, cells migrate, either surrounding the prospective ectoderm contributing to the embryo proper, or into the extra-embryonic region to form the yolk sac, umbilical cord and placenta. Fate mapping has shown that mature tissues such as blood and heart originate from specific regions of the pre-gastrula epiblast, but the plasticity of cells within the embryo and the function of key cell-type-specific transcription factors remain unclear. Here we analyse 1,205 cells from the epiblast and nascent Flk1(+) mesoderm of gastrulating mouse embryos using single-cell RNA sequencing, representing the first transcriptome-wide in vivo view of early mesoderm formation during mammalian gastrulation. Additionally, using knockout mice, we study the function of Tal1, a key haematopoietic transcription factor, and demonstrate, contrary to previous studies performed using retrospective assays, that Tal1 knockout does not immediately bias precursor cells towards a cardiac fate. PMID- 27383784 TI - Corrigendum: Convection in a volatile nitrogen-ice-rich layer drives Pluto's geological vigour. PMID- 27383785 TI - Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma. AB - Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumour suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. Here we show, however, that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN messenger RNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma development with broad implications for cancer pathogenesis. PMID- 27383787 TI - Genetics: Mitochondrial DNA in evolution and disease. PMID- 27383788 TI - Corrigendum: Malaria: Thermoregulation in a parasite's life cycle. PMID- 27383786 TI - TTC39B deficiency stabilizes LXR reducing both atherosclerosis and steatohepatitis. AB - Cellular mechanisms that mediate steatohepatitis, an increasingly prevalent condition in the Western world for which no therapies are available, are poorly understood. Despite the fact that its synthetic agonists induce fatty liver, the liver X receptor (LXR) transcription factor remains a target of interest because of its anti-atherogenic, cholesterol removal, and anti-inflammatory activities. Here we show that tetratricopeptide repeat domain protein 39B (Ttc39b, C9orf52) (T39), a high-density lipoprotein gene discovered in human genome-wide association studies, promotes the ubiquitination and degradation of LXR. Chow-fed mice lacking T39 (T39(-/-)) display increased high-density lipoprotein cholesterol levels associated with increased enterocyte ATP-binding cassette transporter A1 (Abca1) expression and increased LXR protein without change in LXR messenger RNA. When challenged with a high fat/high cholesterol/bile salt diet, T39(-/-) mice or mice with hepatocyte-specific T39 deficiency show increased hepatic LXR protein and target gene expression, and unexpectedly protection from steatohepatitis and death. Mice fed a Western-type diet and lacking low-density lipoprotein receptor (Ldlr(-/-)T39(-/-)) show decreased fatty liver, increased high-density lipoprotein, decreased low-density lipoprotein, and reduced atherosclerosis. In addition to increasing hepatic Abcg5/8 expression and limiting dietary cholesterol absorption, T39 deficiency inhibits hepatic sterol regulatory element-binding protein 1 (SREBP-1, ADD1) processing. This is explained by an increase in microsomal phospholipids containing polyunsaturated fatty acids, linked to an LXRalpha-dependent increase in expression of enzymes mediating phosphatidylcholine biosynthesis and incorporation of polyunsaturated fatty acids into phospholipids. The preservation of endogenous LXR protein activates a beneficial profile of gene expression that promotes cholesterol removal and inhibits lipogenesis. T39 inhibition could be an effective strategy for reducing both steatohepatitis and atherosclerosis. PMID- 27383789 TI - Corrigendum: sFRP2 in the aged microenvironment drives melanoma metastasis and therapy resistance. PMID- 27383791 TI - A photon-photon quantum gate based on a single atom in an optical resonator. AB - That two photons pass each other undisturbed in free space is ideal for the faithful transmission of information, but prohibits an interaction between the photons. Such an interaction is, however, required for a plethora of applications in optical quantum information processing. The long-standing challenge here is to realize a deterministic photon-photon gate, that is, a mutually controlled logic operation on the quantum states of the photons. This requires an interaction so strong that each of the two photons can shift the other's phase by pi radians. For polarization qubits, this amounts to the conditional flipping of one photon's polarization to an orthogonal state. So far, only probabilistic gates based on linear optics and photon detectors have been realized, because "no known or foreseen material has an optical nonlinearity strong enough to implement this conditional phase shift''. Meanwhile, tremendous progress in the development of quantum-nonlinear systems has opened up new possibilities for single-photon experiments. Platforms range from Rydberg blockade in atomic ensembles to single atom cavity quantum electrodynamics. Applications such as single-photon switches and transistors, two-photon gateways, nondestructive photon detectors, photon routers and nonlinear phase shifters have been demonstrated, but none of them with the ideal information carriers: optical qubits in discriminable modes. Here we use the strong light-matter coupling provided by a single atom in a high finesse optical resonator to realize the Duan-Kimble protocol of a universal controlled phase flip (pi phase shift) photon-photon quantum gate. We achieve an average gate fidelity of (76.2 +/- 3.6) per cent and specifically demonstrate the capability of conditional polarization flipping as well as entanglement generation between independent input photons. This photon-photon quantum gate is a universal quantum logic element, and therefore could perform most existing two photon operations. The demonstrated feasibility of deterministic protocols for the optical processing of quantum information could lead to new applications in which photons are essential, especially long-distance quantum communication and scalable quantum computing. PMID- 27383790 TI - Molecular logic behind the three-way stochastic choices that expand butterfly colour vision. AB - Butterflies rely extensively on colour vision to adapt to the natural world. Most species express a broad range of colour-sensitive Rhodopsin proteins in three types of ommatidia (unit eyes), which are distributed stochastically across the retina. The retinas of Drosophila melanogaster use just two main types, in which fate is controlled by the binary stochastic decision to express the transcription factor Spineless in R7 photoreceptors. We investigated how butterflies instead generate three stochastically distributed ommatidial types, resulting in a more diverse retinal mosaic that provides the basis for additional colour comparisons and an expanded range of colour vision. We show that the Japanese yellow swallowtail (Papilio xuthus, Papilionidae) and the painted lady (Vanessa cardui, Nymphalidae) butterflies have a second R7-like photoreceptor in each ommatidium. Independent stochastic expression of Spineless in each R7-like cell results in expression of a blue-sensitive (Spineless(ON)) or an ultraviolet (UV)-sensitive (Spineless(OFF)) Rhodopsin. In P. xuthus these choices of blue/blue, blue/UV or UV/UV sensitivity in the two R7 cells are coordinated with expression of additional Rhodopsin proteins in the remaining photoreceptors, and together define the three types of ommatidia. Knocking out spineless using CRISPR/Cas9 (refs 5, 6) leads to the loss of the blue-sensitive fate in R7-like cells and transforms retinas into homogeneous fields of UV/UV-type ommatidia, with corresponding changes in other coordinated features of ommatidial type. Hence, the three possible outcomes of Spineless expression define the three ommatidial types in butterflies. This developmental strategy allowed the deployment of an additional red-sensitive Rhodopsin in P. xuthus, allowing for the evolution of expanded colour vision with a greater variety of receptors. This surprisingly simple mechanism that makes use of two binary stochastic decisions coupled with local coordination may prove to be a general means of generating an increased diversity of developmental outcomes. PMID- 27383792 TI - High-resolution seismic constraints on flow dynamics in the oceanic asthenosphere. AB - Convective flow in the mantle and the motions of tectonic plates produce deformation of Earth's interior, and the rock fabric produced by this deformation can be discerned using the anisotropy of the seismic wave speed. This deformation is commonly inferred close to lithospheric boundaries beneath the ocean in the uppermost mantle, including near seafloor-spreading centres as new plates are formed via corner flow, and within a weak asthenosphere that lubricates large scale plate-driven flow and accommodates smaller scale convection. Seismic models of oceanic upper mantle differ as to the relative importance of these deformation processes: seafloor spreading fabric is very strong just beneath the crust-mantle boundary (the Mohorovicic discontinuity, or Moho) at relatively local scales, but at the global and ocean-basin scales, oceanic lithosphere typically appears weakly anisotropic when compared to the asthenosphere. Here we use Rayleigh waves, recorded across an ocean-bottom seismograph array in the central Pacific Ocean (the NoMelt Experiment), to provide unique localized constraints on seismic anisotropy within the oceanic lithosphere-asthenosphere system in the middle of a plate. We find that azimuthal anisotropy is strongest within the high-seismic velocity lid, with the fast direction coincident with seafloor spreading. A minimum in the magnitude of azimuthal anisotropy occurs within the middle of the seismic low-velocity zone, and then increases with depth below the weakest portion of the asthenosphere. At no depth does the fast direction correlate with the apparent plate motion. Our results suggest that the highest strain deformation in the shallow oceanic mantle occurs during corner flow at the ridge axis, and via pressure-driven or buoyancy-driven flow within the asthenosphere. Shear associated with motion of the plate over the underlying asthenosphere, if present, is weak compared to these other processes. PMID- 27383793 TI - Mitochondrial and nuclear DNA matching shapes metabolism and healthy ageing. AB - Human mitochondrial DNA (mtDNA) shows extensive within population sequence variability. Many studies suggest that mtDNA variants may be associated with ageing or diseases, although mechanistic evidence at the molecular level is lacking. Mitochondrial replacement has the potential to prevent transmission of disease-causing oocyte mtDNA. However, extension of this technology requires a comprehensive understanding of the physiological relevance of mtDNA sequence variability and its match with the nuclear-encoded mitochondrial genes. Studies in conplastic animals allow comparison of individuals with the same nuclear genome but different mtDNA variants, and have provided both supporting and refuting evidence that mtDNA variation influences organismal physiology. However, most of these studies did not confirm the conplastic status, focused on younger animals, and did not investigate the full range of physiological and phenotypic variability likely to be influenced by mitochondria. Here we systematically characterized conplastic mice throughout their lifespan using transcriptomic, proteomic,metabolomic, biochemical, physiological and phenotyping studies. We show that mtDNA haplotype profoundly influences mitochondrial proteostasis and reactive oxygen species generation,insulin signalling, obesity, and ageing parameters including telomere shortening and mitochondrial dysfunction, resulting in profound differences in health longevity between conplastic strains. PMID- 27383795 TI - Effects of dissolved organic matter on phototransformation rates and dioxin products of triclosan and 2'-HO-BDE-28 in estuarine water. AB - Photochemical transformation of hydroxylated polyhalodiphenyl ethers (HO-PXDEs) has attracted much attention for their ubiquitous presence and the photochemical formation of highly toxic dioxins. Dissolved organic matter (DOM) plays an important role in the environmental photochemical transformation of organic pollutants. However, the effects of DOM on the photolysis kinetics and dioxin formation of HO-PXDEs are still not fully understood. Herein, the effects of Suwannee River natural organic matter (SRNOM) on the phototransformation of 2'-HO 2,4,4'-trichlorodiphenyl ether (triclosan) and 2'-HO-2,4,4'-tribromodiphenyl ether (2'-HO-BDE-28) were investigated in artificial estuarine water (AEW). The results showed that although SRNOM induced indirect photolysis of triclosan and 2'-HO-BDE-28, it decreased the observed photolytic rate constants due to light screening, static quenching and dynamic quenching effects. The above effects were quantified firstly. Direct photolysis is more important than indirect photolysis in the transformation of the target compounds and the production of dioxins. SRNOM increased the dioxin yields of the two HO-PXDEs. It was also found that SRNOM decreased the formation rate constant (kp) of 2,8-dichlorodibenzo-p-dioxin (2,8-DCDD) from triclosan and showed no obvious influence on the kp of 2,8 dibromodibenzo-p-dioxin (2,8-DBDD) from 2'-HO-BDE-28. SRNOM showed no obvious influence on the degradation of 2,8-DCDD, while it increased the degradation rate constant of 2,8-DBDD. The promoting effect on the degradation of 2,8-DBDD was attributed to the formation of chloride radicals with the concurrence of SRNOM and Cl(-) in AEW. This study revealed the roles of SRNOM in the photochemical transformation of HO-PXDEs and the photochemical formation and degradation of dioxins, which is important for elucidating the transformation fate of HO-PXDEs in aquatic environments. PMID- 27383794 TI - The mechanism of RNA 5' capping with NAD+, NADH and desphospho-CoA. AB - The chemical nature of the 5' end of RNA is a key determinant of RNA stability, processing, localization and translation efficiency, and has been proposed to provide a layer of 'epitranscriptomic' gene regulation. Recently it has been shown that some bacterial RNA species carry a 5'-end structure reminiscent of the 5' 7-methylguanylate 'cap' in eukaryotic RNA. In particular, RNA species containing a 5'-end nicotinamide adenine dinucleotide (NAD+) or 3'-desphospho coenzyme A (dpCoA) have been identified in both Gram-negative and Gram-positive bacteria. It has been proposed that NAD+, reduced NAD+ (NADH) and dpCoA caps are added to RNA after transcription initiation, in a manner analogous to the addition of 7-methylguanylate caps. Here we show instead that NAD+, NADH and dpCoA are incorporated into RNA during transcription initiation, by serving as non-canonical initiating nucleotides (NCINs) for de novo transcription initiation by cellular RNA polymerase (RNAP). We further show that both bacterial RNAP and eukaryotic RNAP II incorporate NCIN caps, that promoter DNA sequences at and upstream of the transcription start site determine the efficiency of NCIN capping, that NCIN capping occurs in vivo, and that NCIN capping has functional consequences. We report crystal structures of transcription initiation complexes containing NCIN-capped RNA products. Our results define the mechanism and structural basis of NCIN capping, and suggest that NCIN-mediated 'ab initio capping' may occur in all organisms. PMID- 27383796 TI - Construction of Bacillus subtilis strain engineered for expression of porcine beta-defensin-2/cecropin P1 fusion antimicrobial peptides and its growth promoting effect and antimicrobial activity. AB - OBJECTIVE: To generate recombinant Bacillus subtilis (B. subtilis) engineered for expression of porcine beta-defensin-2 (pBD-2) and cecropin P1 (CP1) fusion antimicrobial peptide and investigate their anti-bacterial activity in vitro and their growth-promoting and disease resisting activity in vivo. METHODS: The pBD-2 and CP1 fused gene was synthesized using the main codons of B. subtilis and inserted into plasmid pMK4 vector to construct their expression vector. The fusion peptide-expressing B. subtilis was constructed by transformation with the vector. The expressed fusion peptide was detected with Western blot. The antimicrobial activity of the expressed fusion peptide and the recovered pBD-2 and CP1 by enterokinase digestion in vitro was analyzed by the bacterial growth inhibitory activity assay. To analyze the engineered B. subtilis on growth promotion and disease resistance, the weaned piglets were fed with basic diet supplemented with the recombinant B. subtilis. Then the piglets were challenged by enteropathogenic Escherichia coli (E. coli). The weight gain and diarrhea incidence of piglets were measured after challenge. RESULTS: The recombinant B. subtilis engineered for expression of pBD-2/CP1 fusion peptide was successfully constructed using the main codons of the B. subtilis. Both expressed pBD-2/CP1 fusion peptide and their individual peptides recovered from parental fusion peptide by enterokinase digestion possessed the antimicrobial activities to a variety of the bacteria, including gram-negative bacteria (E. coli, Salmonella typhimurium, and Haemophilus parasuis) and gram-positive bacteria (Staphylococcus aureus). Supplementing the engineered B. subtilis to the pig feed could significantly promote the piglet growth and reduced diarrhea incidence of the piglets. CONCLUSION: The generated B. subtilis strain can efficiently express pBD 2/CP1 fusion antimicrobial peptide, the recovered pBD-2 and CP1 peptides possess potent antimicrobial activities to a variety of bacterial species in vitro. Supplementation of the engineered B. subtilis in pig feed obviously promote piglet growth and resistance to the colibacillosis. PMID- 27383797 TI - Effects of graded levels of cupric citrate on growth performance, antioxidant status, serum lipid metabolites and immunity, and tissue residues of trace elements in weaned pigs. AB - OBJECTIVE: The goal of this study was to investigate the effects of cupric citrate (CuCit) on growth performance, antioxidant indices, serum lipid metabolites, serum immune indices, and tissue residues of copper (Cu), zinc, and iron in weaned pigs. METHODS: A total of 180 weaned pigs (Duroc*Landrace*Large White) with an average body weight of 8.98+/-1.21 kg were randomly assigned to a corn-soybean meal control ration, or 4 similar rations with 30, 60, 120, or 240 mg/kg Cu as CuCit. All diets contained 10 mg/kg Cu as cupric sulfate from the vitamin-mineral premix. The experiment was divided into two phases: 0 to 14 d (phase 1) and 15 to 28 d (phase 2). RESULTS: Average daily gain (ADG; linearly, p<0.01) and average daily feed intake (ADFI; linearly and quadratically, p<0.05) were affected by an increase in CuCit during phase 2. Overall period, ADG (p<0.05) and ADFI (p<0.01) were linearly increased with increasing dietary levels of CuCit. Serum malondialdehyde concentrations (p<0.05) and glutathione peroxidase activity (p<0.01) linearly decreased and increased respectively with an increase in CuCit. Serum levels of Cu-Zn superoxide dismutase were linearly affected with an increase in CuCit (p<0.01). Hepatic malondialdehyde levels decreased with an increase in CuCit (linearly and quadratically, p<0.01). Serum total cholesterol concentrations were quadratically affected (p<0.05) and decreased in pigs fed Cu as CuCit at 60 and 120 mg/kg and increased in pigs fed 240 mg/kg Cu as CuCit. Serum high-density lipoprotein concentrations were linearly affected with an increase in CuCit (p<0.01). Serum IL-1beta levels were quadratically affected (p<0.05) by dietary treatment. Compared with other treatments, 240 mg/kg Cu from CuCit quadratically increased hepatic (p<0.01) and renal (p<0.05) Cu concentrations, and quadratically decreased hepatic and renal iron concentrations (p<0.05). CONCLUSION: Cu administered in the form of CuCit at a dosage range of 30 to 60 mg/kg, effectively enhanced the growth performance and antioxidant status of weaned pigs. PMID- 27383798 TI - Characterization of the microbial communities along the gastrointestinal tract of sheep by 454 pyrosequencing analysis. AB - OBJECTIVE: The gastrointestinal tract of sheep contain complex microbial communities that influence numerous aspects of the sheep's health and development. The objective of this study was to analyze the composition and diversity of the microbiota in the gastrointestinal tract sections (rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of sheep. METHODS: This analysis was performed by 454 pyrosequencing using the V3 V6 region of the 16S rRNA genes. Samples were collected from five healthy, small tailed Han sheep aged 10 months, obtained at market. The bacterial composition of sheep gastrointestinal microbiota was investigated at the phylum, class, order, family, genus, and species levels. RESULTS: The dominant bacterial phyla in the entire gastrointestinal sections were Firmicutes, Bacteroidetes, and Proteobacteria. In the stomach, the three most dominant genera in the sheep were Prevotella, unclassified Lachnospiraceae, and Butyrivibrio. In the small intestine, the three most dominant genera in the sheep were Escherichia, unclassified Lachnospiraceae, and Ruminococcus. In the large intestine, the three most dominant genera in the sheep were Ruminococcus, unclassified Ruminococcaceae, and Prevotella. R. flavefaciens, B. fibrisolvens, and S. ruminantium were three most dominant species in the sheep gastrointestinal tract. Principal Coordinates Analysis showed that the microbial communities from each gastrointestinal section could be separated into three groups according to similarity of community composition: stomach (rumen, reticulum, omasum, and abomasum), small intestine (duodenum, jejunum, and ileum), and large intestine (cecum, colon, and rectum). CONCLUSION: This is the first study to characterize the entire gastrointestinal microbiota in sheep by use of 16S rRNA gene amplicon pyrosequencing, expanding our knowledge of the gastrointestinal bacterial community of sheep. PMID- 27383799 TI - Effects of alanyl-glutamine supplementation on the small intestinal mucosa barrier in weaned piglets. AB - OBJECTIVE: The study was to investigate the effects of alanyl-glutamine (Ala-Gln) and glutamine (Gln) supplementation on the intestinal mucosa barrier in piglets. METHODS: A total of 180 barrows with initial weight 10.01+/-0.03 kg were randomly allocated to three treatments, and each treatment consisted of three pens and twenty pigs per pen. The piglets of three groups were fed with control diet [0.62% alanine (Ala)], Ala-Gln diet (0.5% Ala-Gln), Gln diet (0.34% Gln and 0.21% Ala), respectively. RESULTS: The results showed that in comparison with control diet, dietary Ala-Gln supplementation increased the height of villi in duodenum and jejunum (p<0.05), Gln supplementation increased the villi height of jejunum (p<0.05), Ala-Gln supplementation up-regulated the mRNA expressions of epidermal growth factor receptor and insulin-like growth factor 1 receptor in jejunal mucosa (p<0.05), raised the mRNA expressions of Claudin-1, Occludin, zonula occludens protein-1 (ZO-1) and the protein levels of Occludin, ZO-1 in jejunal mucosa (p<0.05), Ala-Gln supplementation enlarged the number of goblet cells in duodenal and ileal epithelium (p<0.05), Gln increased the number of goblet cells in duodenal epithelium (p<0.05) and Ala-Gln supplementation improved the concentrations of secretory immunoglobulin A and immunoglobulin G in the jejunal mucosa (p<0.05). CONCLUSION: These results demonstrated that dietary Ala-Gln supplementation could maintain the integrity of small intestine and promote the functions of intestinal mucosa barriers in piglets. PMID- 27383800 TI - Improvement of Milk Fatty Acid Composition for Production of Functional Milk by Dietary Phytoncide Oil Extracted from Discarded Pine Nut Cones (Pinus koraiensis) in Holstein Dairy Cows. AB - This study was conducted to examine the effects of adding phytoncide oil extracted from Korean pine nut cone byproduct to the diet of dairy cows on milk yield and compositions, fatty acid characteristics, complete blood count and stress response. A total of 74 Holstein cows were used for 30 days and divided into two groups. Each group was given a basal diet (C) or an experimental diet containing phytoncide additives at 0.016% (T) in feed. The results showed that phytoncide feeding had no effect on milk yield. In addition, there were no observed effects on milk composition, but the ratio of fatty acid in milk was significantly affected by the phytoncide diet, and it showed a positive effect. Not only were the major functional fatty acids, conjugated linoleic acid and eicosapentaenoic acid increased, but also omega6:omega3 fatty acid ratio was reduced in milk of T group (p<0.05). In blood analysis, the complete blood count showed no significant difference between C and T group on all parameters. However, the cortisol concentration was significantly decreased in T group compared to control (p<0.05). Taken together, we suggest that phytoncide oil does not have a great influence on the physiological changes, but can be a potential feed additive that improves the milk fatty acid and stress resilience in dairy cows. In addition, it will contribute to the development of feed resource, a reduction in feed cost and a lessening of environmental pollution. PMID- 27383801 TI - The effect of partial substitution of roasted soybean seed with graded levels of sweet potato (Ipomoea batatas) leaf meal on growth performances and carcass characteristics of broiler chickens. AB - This study was designed to assess the effects of partial substitution of roasted soybean seed with sweet potato (Ipomoea batatas) leaf meal (SPLM) on growth performances and carcass components of broiler chickens. The experiment was a completely randomized design consisting of five dietary treatments replicated four times with ten chicks each. The control diet (treatment 1, T1) contained roasted soybean seed as the major protein source without SPLM and treatment diets containing SPLM at the levels of 30 g/kg (treatment 2, T2), 60 g/kg (treatment 3, T3), 90 g/kg (treatment 4, T4) and 120 g/kg (treatment 5, T5) by partially substituting the roasted soybean seed in the control diet. The results indicated that the body weight gain in chickens reared in T1 was (p<0.01) higher than those fed on T3, T4 and T5 diets. The individual feed intake in chickens reared in T1 was (p<0.001) higher than those fed on other treatment diets. The feed conversion ratio (kg feed/kg gain) of chickens fed on T1 was (p<0.05) lower than those reared in T4 and T5 diets. Chickens fed with T2 diet had numerically higher values of slaughter, dressed carcass and breast than those reared in T4 and T5 diets. It can be concluded that the partial substitution of roasted soybean seed with sweet potato leaf might be economically feasible feeding strategy of broiler chickens in smallholder poultry farm settings. PMID- 27383802 TI - A Major Locus for Quantitatively Measured Shank Skin Color Traits in Korean Native Chicken. AB - Shank skin color of Korean native chicken (KNC) shows large color variations. It varies from white, yellow, green, bluish or grey to black, whilst in the majority of European breeds the shanks are typically yellow-colored. Three shank skin color-related traits (i.e., lightness [L*], redness [a*], and yellowness [b*]) were measured by a spectrophotometer in 585 progeny from 68 nuclear families in the KNC resource population. We performed genome scan linkage analysis to identify loci that affect quantitatively measured shank skin color traits in KNC. All these birds were genotyped with 167 DNA markers located throughout the 26 autosomes. The SOLAR program was used to conduct multipoint variance-component quantitative trait locus (QTL) analyses. We detected a major QTL that affects b* value (logarithm of odds [LOD] = 47.5, p = 1.60*10-49) on GGA24 (GGA for Gallus gallus). At the same location, we also detected a QTL that influences a* value (LOD = 14.2, p = 6.14*10-16). Additionally, beta-carotene dioxygenase 2 (BCDO2), the obvious positional candidate gene under the linkage peaks on GGA24, was investigated by the two association tests: i.e., measured genotype association (MGA) and quantitative transmission disequilibrium test (QTDT). Significant associations were detected between BCDO2 g.9367 A>C and a* (PMGA = 1.69*10-28; PQTDT = 2.40*10-25). The strongest associations were between BCDO2 g.9367 A>C and b* (PMGA = 3.56*10-66; PQTDT = 1.68*10-65). However, linkage analyses conditional on the single nucleotide polymorphism indicated that other functional variants should exist. Taken together, we demonstrate for the first time the linkage and association between the BCDO2 locus on GGA24 and quantitatively measured shank skin color traits in KNC. PMID- 27383803 TI - Accuracy of genomic breeding value prediction for intramuscular fat using different genomic relationship matrices in Hanwoo (Korean cattle). AB - OBJECTIVE: Intramuscular fat is one of the meat quality traits that is considered in the selection strategies for Hanwoo (Korean cattle). Different methods are used to estimate the breeding value of selection candidates. In the present work we focused on accuracy of different genotype relationship matrices as described by forni and pedigree based relationship matrix. METHODS: The data set included a total of 778 animals that were genotyped for BovineSNP50 BeadChip. Among these 778 animals, 72 animals were sires for 706 reference animals and were used as a validation dataset. Single trait animal model (best linear unbiased prediction and genomic best linear unbiased prediction) was used to estimate the breeding values from genomic and pedigree information. RESULTS: The diagonal elements for the pedigree based coefficients were slightly higher for the genomic relationship matrices (GRM) based coefficients while off diagonal elements were considerably low for GRM based coefficients. The accuracy of breeding value for the pedigree based relationship matrix (A) was 13% while for GRM (GOF, G05, and Yang) it was 0.37, 0.45, and 0.38, respectively. CONCLUSION: Accuracy of GRM was 1.5 times higher than A in this study. Therefore, genomic information will be more beneficial than pedigree information in the Hanwoo breeding program. PMID- 27383804 TI - Comparison of Muscle Fiber and Meat Quality Characteristics in Different Japanese Quail Lines. AB - The aim of this study was to compare the growth performance, fiber characteristics of the pectoralis major muscle, and meat quality characteristics in the heavy weight (HW) and random bred control (RBC) quail lines and genders. The HW male exhibited more than two times greater body (245.7 vs 96.1 g, p<0.05) and pectoralis major muscle (PMW; 37.1 vs 11.1 g, p<0.05) weights compared to the RBC female. This growth performance in the HW line was associated with a greater muscle fiber area (1,502 vs 663.0 MUm(2), p<0.001) compared to the RBC line. Greater muscle mass of the HW male was accompanied by a higher percentage of type IIB fiber compared to the HW female (64.0% vs 51.0%, p<0.05). However, muscle fiber hyperplasia (increase in fiber number) has had a somewhat limited effect on PMW between the two lines. On the other hand, the HW line harboring a higher proportion of type IIB fiber showed rapid pH decline at the early postmortem period (6.23 vs 6.41, p<0.05) and lighter meat surface (53.5 vs 47.3, p<0.05) compared to the RBC line harboring a lower proportion of type IIB fiber. There were no significant differences observed in the measurement of water-holding capacity including drip loss (2.74% vs 3.07%, p>0.05) and cooking loss (21.9% vs 20.4%, p>0.05) between the HW and RBC lines. Therefore, the HW quail line developed by selection from the RBC quail, was slightly different in the meat quality characteristics compared to the RBC line, and a marked difference was found in growth performance between the two quail lines. PMID- 27383805 TI - Lignosulfonic acid promotes hypertrophy in 3T3-L1 cells without increasing lipid content and increases their 2-deoxyglucose uptake. AB - OBJECTIVE: Adipose tissue plays a key role in the development of obesity and diabetes. We previously reported that lignosulfonic acid suppresses the rise in blood glucose levels through the inhibition of alpha-glucosidase activity and intestinal glucose absorption. The purpose of this study is to examine further biological activities of lignosulfonic acid. METHODS: In this study, we examined the effect of lignosulfonic acid on differentiation of 3T3-L1 cells. RESULTS: While lignosulfonic acid inhibited proliferation (mitotic clonal expansion) after induction of differentiation, lignosulfonic acid significantly increased the size of accumulated lipid droplets in the cells. Semi-quantitative reverse transcription polymerase chain reaction analysis showed that lignosulfonic acid increased the expression of the adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARgamma), leading to increased glucose transporter 4 (Glut-4) expression and 2-deoxyglucose uptake in differentiated 3T3 L1 cells. Additionally, feeding lignosulfonic acid to diabetic KK-Ay mice suppressed increase of blood glucose level. CONCLUSION: Lignosulfonic acid may be useful as a functional anti-diabetic component of food. PMID- 27383806 TI - Microbial composition in different gut locations of weaning piglets receiving antibiotics. AB - OBJECTIVE: The aim of this study was to examine shifts in the composition of the bacterial population in the intestinal tracts (ITs) of weaning piglets by antibiotic treatment using high-throughput sequencing. METHODS: Sixty 28-d-old weaning piglets were randomly divided into two treatment groups. The Control group was treated with a basal diet without antibiotics. The Antibiotic group's basal diet contained colistin sulfate at a concentration of 20 g per ton and bacitracin zinc at a concentration of 40 g per ton. All of the pigs were fed for 28 days. Then, three pigs were killed, and the luminal contents of the jejunum, ileum, cecum, and colon were collected for DNA extraction and high-throughput sequencing. RESULTS: The results showed that the average daily weight gain of the antibiotic group was significantly greater (p<0.05), and the incidence of diarrhea lower (p>0.05), than the control group. A total of 812,607 valid reads were generated. Thirty-eight operational taxonomic units (OTUs) that were found in all of the samples were defined as core OTUs. Twenty-one phyla were identified, and approximately 90% of the classifiable sequences belonged to the phylum Firmicutes. Forty-two classes were identified. Of the 232 genera identified, nine genera were identified as the core gut microbiome because they existed in all of the tracts. The proportion of the nine core bacteria varied at the different tract sites. A heat map was used to understand how the numbers of the abundant genera shifted between the two treatment groups. CONCLUSION: At different tract sites the relative abundance of gut microbiota was different. Antibiotics could cause shifts in the microorganism composition and affect the composition of gut microbiota in the different tracts of weaning piglets. PMID- 27383807 TI - Effects of different ratios and storage periods of liquid brewer's yeast mixed with cassava pulp on chemical composition, fermentation quality and in vitro ruminal fermentation. AB - OBJECTIVE: This study aims to evaluate the chemical composition, fermentation quality and in vitro ruminal fermentation of various ratios and storage periods of liquid brewer's yeast (LBY) mixed with cassava pulp (CVP). METHODS: Four mixtures of fresh LBY and CVP were made (LBY0, LBY10, LBY20, and LBY30 for LBY:CVP at 0:100, 10:90, 20:80, and 30:70, respectively) on a fresh matter basis, in 500 g in plastic bags and stored at 30 to 32 degrees C. After storage, the bags were opened weekly from weeks 0 to 4. Fermentation quality and in vitro gas production (IVGP) were determined, as well as the dry matter (DM), organic matter (OM), crude protein (CP), ether extract (EE), neutral detergent fiber, acid detergent fiber and acid detergent lignin contents. RESULTS: The contents of CP and EE increased, whereas all other components decreased, in proportion to LBY inclusion (p<0.01). The DM and OM contents gradually decreased in weeks 3 and 4 (p<0.05), while EE contents were lowest in week 0. The pH, ammonia nitrogen per total nitrogen (NH3-N/TN) and V-score in each mixture and storage period demonstrated superior fermentation quality (pH<=4.2, NH3-N/TN<=12.5%, and V score>90%). The pH increased and NH3-N/TN decreased, with proportionate increases of LBY, whereas the pH decreased and NH3-N/TN increased, as the storage periods were extended (p<0.01). Although IVGP decreased in proportion to the amount of LBY inclusion (p<0.01), in vitro organic matter digestibility (IVOMD) was unaffected by the mixture ratios. The highest IVGP and IVOMD were observed in week 0 (p<0.01). CONCLUSION: The inclusion of LBY (as high as 30%) into CVP improves the chemical composition of the mixture, thereby increasing the CP content, while decreasing IVGP, without decreasing fermentation quality and IVOMD. In addition, a preservation period of up to four weeks can guarantee superior fermentation quality in all types of mixtures. Therefore, we recommend limiting the use of CVP as a feed ingredient, given its low nutritional value and improving feed quality with the inclusion of LBY. PMID- 27383808 TI - Characterization of Heterologously Expressed Acetyl Xylan Esterase1 Isolated from the Anaerobic Rumen Fungus Neocallimastix frontalis PMA02. AB - Acetyl xylan esterase (AXE), which hydrolyzes the ester linkages of the naturally acetylated xylan and thus known to have an important role for hemicellulose degradation, was isolated from the anaerobic rumen fungus Neocallimastix frontatlis PMA02, heterologously expressed in Escherichi coli (E.coli) and characterized. The full-length cDNA encoding NfAXE1 was 1,494 bp, of which 978 bp constituted an open reading frame. The estimated molecular weight of NfAXE1 was 36.5 kDa with 326 amino acid residues, and the calculated isoelectric point was 4.54. The secondary protein structure was predicted to consist of nine alpha helixes and 12 beta-strands. The enzyme expressed in E.coli had the highest activity at 40 degrees C and pH 8. The purified recombinant NfAXE1 had a specific activity of 100.1 U/mg when p-nitrophenyl acetate (p-NA) was used as a substrate at 40 degrees C, optimum temperature. The amount of liberated acetic acids were the highest and the lowest when p-NA and acetylated birchwood xylan were used as substrates, respectively. The amount of xylose released from acetylated birchwod xylan was increased by 1.4 fold when NfAXE1 was mixed with xylanase in a reaction cocktail, implying a synergistic effect of NfAXE1 with xylanase on hemicellulose degradation. PMID- 27383809 TI - Evaluation of gaseous concentrations, bacterial diversity and microbial quantity in different layers of deep litter system. AB - OBJECTIVE: An experiment was conducted to investigate the environment of the deep litter system and provided theoretical basis for production. METHODS: The bedding samples were obtained from a pig breeding farm and series measurements associated with gases concentrations and the bacterial diversity as well as the quantity of Escherichia coli, Lactobacilli, Methanogens were performed in this paper. RESULTS: The concentrations of CO2, CH4, and NH3 in the deep litter system increased with the increasing of depth while the N2O concentrations increased fiercely from the 0 cm to the -10 cm depth but then decreased beneath the -10 cm depth. Meanwhile, the Shannon index, the dominance index as well as the evenness index at the -20 cm layer was significantly different from the other layers (p<0.05). On the other hand, the quantity of Escherichia coli reached the highest value at the surface beddings and there was a significant drop at the -20 cm layer with the increasing depth. The Lactobacilli numbers increased with the depth from 0 cm to -15 cm and then decreased significantly under the -20 cm depth. The expression of Methanogens reached its largest value at the depth of 35 cm. CONCLUSION: The upper layers (0 cm to -5 cm) of this system were aerobic, the middle layers (-10 cm to -20 cm) were micro-aerobic, while that the bottom layers (below -20 cm depth) were anaerobic. In addition, from a standpoint of increasing the nitrification pathway and inhibiting the denitrification pathway, it should be advised that the deep litter system should be kept aerobic. PMID- 27383810 TI - Molecular characterization and expression pattern of a novel Keratin-associated protein 11.1 gene in the Liaoning cashmere goat (Capra hircus). AB - OBJECTIVE: An experiment was conducted to determine the relationship between the KAP11.1 and the regulation wool fineness. METHODS: In previous work, we constructed a skin cDNA library and isolated a full-length cDNA clone termed KAP11.1. On this basis, we conducted a series of bioinformatics analysis. Tissue distribution of KAP11.1 mRNA was performed using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis. The expression of KAP11.1 mRNA in primary and secondary hair follicles was performed using real time PCR (real-time polymerase chain reaction) analysis. The expression location of KAP11.1 mRNA in primary and secondary hair follicles was performed using in situ hybridization. RESULTS: Bioinformatics analysis showed that KAP11.1 gene encodes a putative 158 amino acid protein that exhibited a high content of cysteine, serine, threonine, and valine and has a pubertal mammary gland) structural domain. Secondary structure prediction revealed a high proportion of random coils (76.73%). Semi-quantitative RT-PCR showed that KAP11.1 gene was expressed in heart, skin, and liver, but not expressed in spleen, lung and kidney. Real time PCR results showed that the expression of KAP11.1 has a higher expression in catagen than in anagen in the primary hair follicles. However, in the secondary hair follicles, KAP11.1 has a significantly higher expression in anagen than in catagen. Moreover, KAP11.1 gene has a strong expression in inner root sheath, hair matrix, and a lower expression in hair bulb. CONCLUSION: We conclude that KAP11.1 gene may play an important role in regulating the fiber diameter. PMID- 27383811 TI - High pressure processing for dark-firm-dry beef: effect on physical properties and oxidative deterioration during refrigerated storage. AB - OBJECTIVE: Study on the application of high pressure processing (HPP) for dark firm-dry (DFD) beef was conducted to observe whether HPP has any impact on physical properties and to evaluate oxidative deterioration during refrigerated storage under vacuum. METHODS: The longissimus lumborum muscles obtained from Friesian Holstein steers (33+/-0.5 months old) with 24-h postmortem pH higher than 6.0 were vacuum-packed and subjected to pressurization at 200, 400, and 600 MPa for 180 s at 15 degrees C+/-2 degrees C; the samples were then stored for 9 days at 4 degrees C+/-1 degrees C and compared with control (0.1 MPa). RESULTS: HPP increased meat pH by 0.1 to 0.2 units and the tenderness of cooked DFD beef significantly with no significant effects on meat texture profile. The stability of meat pH was well maintained during refrigerated storage under vacuum. No clear effects were found on the activity of catalase and superoxide dismutase, however, glutathione peroxidase activity was significantly reduced by high pressure. HPP and storage time resulted in aroma changes and the increasing amount of malondialdehyde and metmyoglobin relative composition. CONCLUSION: Although the increasing amount of malondialdehyde content, metmyoglobin formation and aroma changes in HPP-treated samples could not be avoided, HPP at 200 MPa increased L* and a* values with less discoloration and oxidative deterioration during storage. PMID- 27383812 TI - Effects of conjugated linoleic acid on the performance of laying hens, lipid composition of egg yolk, egg flavor, and serum components. AB - OBJECTIVE: This experiment investigated the effects of dietary supplementation with conjugated linoleic acid (CLA) on the serum components, laying hen productivity, lipid composition of egg yolk, egg flavor and egg quality. METHODS: Healthy 28-week-old Hy-Line white laying hens (n = 480) were divided randomly into 4 groups, 6 replicates/group, 20 birds/replicate. The 30-day experimental diets included 0% (control), 0.4%, 0.8%, and 1.6% CLA. Some serum indices of the birds, and egg production, quality, fatty acid composition, egg quality were measured. RESULTS: The dietary supplementation with 0.4%, 0.8%, and 1.6% CLA did not significantly affect the laying rate and feed intake, as well as calcium ion and phosphorus ion concentration in serum (p>0.05). However, the CLA had significantly increased the strength of eggshell, decreased the odor, flavor, and taste of egg yolk, deepened the color of egg yolk, increased saturated fatty acids and polyunsaturated fatty acids, and reduced the monounsaturated fatty acids (p<0.05). On the other hand, the dietary supplementation with 1.6% CLA had significant effects on feed/gain, and improved serum hormones. Dietary supplementation with 0.4% and 0.8% CLA can significantly enhance the activity of alkaline phosphates. CONCLUSION: CLA has no effect on production performance, but does enhance the lipid content of the egg yolk and the strength of the eggshell. PMID- 27383813 TI - Effect of supplementation of yeast with bacteriocin and Lactobacillus culture on growth performance, cecal fermentation, microbiota composition, and blood characteristics in broiler chickens. AB - OBJECTIVE: The aim of the present study was to investigate the effect of yeast with bacteriocin and Lactobacillus cultures (mixture of Lactobacillus agilis BCRC 10436 and Lactobacillus reuteri BCRC 17476) supplements, alone or in combination, on broiler chicken performance. METHODS: A total of 300, 1-d-old healthy broiler chickens were randomly divided into five treatment groups: i) basal diet (control), ii) basal diet+0.25% yeast (Saccharomyces cerevisiae) (YC), iii) basal diet+0.25% yeast with bacteriocin (BA), iv) basal diet+Lactobacillus cultures (LAB), and v) basal diet +0.25% yeast with bacteriocin+Lactobacillus cultures (BA+LAB). Growth performance, cecal microbiota, cecal fermentation products, and blood biochemistry parameters were determined when chickens were 21 and 35 d old. RESULTS: The supplementation of YC, BA, and BA+LAB resulted in a significantly better feed conversion rate (FCR) than that of the control group during 1 to 21 d (p<0.05). The LAB supplementation had a significant effect on the presence of Lactobacillus in the ceca at 35 d. None of the supplements had an effect on relative numbers of L. agilis and L. reuter at 21 d, but the BA supplementation resulted in the decrease of both Lactobacillus strains at 35 d. The BA+LAB supplementation resulted in higher short chain fatty acid (SCFA) in the ceca, but LAB supplementation significantly decreased the SCFA at 35 d (p<0.05). All treatments tended to decrease ammonia concentration in the ceca at 21 d, especially in the LAB treatment group. The BA supplementation alone decreased the triacylglycerol (TG) concentration significantly at 21 d (p<0.05), but the synergistic effect of BA and LAB supplementation was required to reduce the TG concentration at 35 d. The YC supplementation tended to increase the plasma cholesterol at 21 d and 35 d. However, the BA supplementation significantly decreased the cholesterol and low density lipoprotein cholesterol level at 35 d. In conclusion, the BA+LAB supplementation was beneficial to body weight gain and FCR of broiler chickens. CONCLUSION: The effect of BA and LAB supplementation may be a result of the growth of lactic acid bacteria enhancement and physiological characterization of bacteriocin, and it suggests that the BA and LAB supplementation level or Lactobacillus strain selection should be integrated in future supplementation designs. PMID- 27383814 TI - Effect of Triclosan-Coated Suture and Antibiotic Prophylaxis on Infection and Recurrence after Karydakis Flap Repair for Pilonidal Disease: A Randomized Parallel-Arm Double-Blinded Clinical Trial. AB - BACKGROUND: Pilonidal sinus disease was first described by Mayo in 1833 as "a cyst that contains hair." Although surgical treatment of the lesions can have successful outcomes, it also can be associated with relatively high rates of post operative infectioins and recurrence. Many studies have demonstrated that triclosan-coated sutures (TCS) decrease surgical site infections. OBJECTIVE: The goal of this randomized parallel-arm double-blind clinical trial was to investigate the ability of antibiotic prophylaxis, and secondarily of antibiotic coated sutures, to prevent post-operative infections in the surgical management of pilonidal sinus disease. PATIENTS AND METHODS: The initial trial protocol aimed to compare early infections in patients who did and did not undergo antibiotic prophylaxis (AP(+) vs. AP(-)). A secondary goal was to compare the effects of TCS and conventional sutures (CS) on early infectious complication rates in the two groups. The AP(-) arm had to be terminated prematurely because of an unacceptably high rate of infectious complications. RESULTS: A total of 80 micro-organisms were recovered from 74 patients (69.8%). Methicillin-susceptible coagulase-negative staphylococci were the most common isolates (30%). The most frequently detected anaerobic micro-organism was Actinomyces israelii (7.5%). The TCS and CS groups had similar rates of micro-organism growth (65.8% vs. 75.0%). There was no significant difference in the occurrence of wound dehiscence. Over the six-month follow-up, there were two recurrences, both in the TCS group. The difference was not significant. CONCLUSIONS: We believe that antibiotic prophylaxis is necessary in patients scheduled for Karydakis flap repair. In our study, TCS tended to be associated with a lower rate of infection, but this trend did not achieve statistical significance. Anaerobic micro-organisms dominated the infective isolates. PMID- 27383815 TI - Tree phylogenetic diversity promotes host-parasitoid interactions. AB - Evidence from grassland experiments suggests that a plant community's phylogenetic diversity (PD) is a strong predictor of ecosystem processes, even stronger than species richness per se This has, however, never been extended to species-rich forests and host-parasitoid interactions. We used cavity-nesting Hymenoptera and their parasitoids collected in a subtropical forest as a model system to test whether hosts, parasitoids, and their interactions are influenced by tree PD and a comprehensive set of environmental variables, including tree species richness. Parasitism rate and parasitoid abundance were positively correlated with tree PD. All variables describing parasitoids decreased with elevation, and were, except parasitism rate, dependent on host abundance. Quantitative descriptors of host-parasitoid networks were independent of the environment. Our study indicates that host-parasitoid interactions in species rich forests are related to the PD of the tree community, which influences parasitism rates through parasitoid abundance. We show that effects of tree community PD are much stronger than effects of tree species richness, can cascade to high trophic levels, and promote trophic interactions. As during habitat modification phylogenetic information is usually lost non-randomly, even species rich habitats may not be able to continuously provide the ecosystem process parasitism if the evolutionarily most distinct plant lineages vanish. PMID- 27383816 TI - Madagascar's ephemeral palaeo-grazer guild: who ate the ancient C4 grasses? PMID- 27383817 TI - The anti-predator role of within-nest emergence synchrony in sea turtle hatchlings. AB - Group formation is a common behaviour among prey species. In egg-laying animals, despite the various factors that promote intra-clutch variation leading to asynchronous hatching and emergence from nests, synchronous hatching and emergence occurs in many taxa. This synchrony may be adaptive by reducing predation risk, but few data are available in any natural system, even for iconic examples of the anti-predator function of group formation. Here, we show for the first time that increased group size (number of hatchlings emerging together from a nest) reduces green turtle (Chelonia mydas) hatchling predation. This effect was only observed earlier in the night when predation pressure was greatest, indicated by the greatest predator abundance and a small proportion of predators preoccupied with consuming captured prey. Further analysis revealed that the effect of time of day was due to the number of hatchlings already killed in an evening; this, along with the apparent lack of other anti-predatory mechanisms for grouping, suggests that synchronous emergence from a nest appears to swamp predators, resulting in an attack abatement effect. Using a system with relatively pristine conditions for turtle hatchlings and their predators provides a more realistic environmental context within which intra-nest synchronous emergence has evolved. PMID- 27383818 TI - Commensal associations and benthic habitats shape macroevolution of the bivalve clade Galeommatoidea. AB - The great diversity of marine life has been shaped by the interplay between abiotic and biotic factors. Among different biotic interactions, symbiosis is an important yet less studied phenomenon. Here, we tested how symbiotic associations affected marine diversification, using the bivalve superfamily Galeommatoidea as a study system. This superfamily contains large numbers of obligate commensal as well as free-living species and is therefore amenable to comparative approaches. We constructed a global molecular phylogeny of Galeommatoidea and compared macroevolutionary patterns between free-living and commensal lineages. Our analyses inferred that commensalism/sediment-dwelling is likely to be the ancestral condition of Galeommatoidea and that secondary invasions of hard-bottom habitats linked to the loss of commensalism. One major clade containing most of the free-living species exhibits a 2-4 times higher diversification rate than that of the commensals, likely driven by frequent niche partitioning in highly heterogeneous hard-bottom habitats. However, commensal clades show much higher within-clade morphological disparity, likely promoted by their intimate associations with diverse hosts. Our study highlights the importance of interactions between different ecological factors in shaping marine macroevolution and that biotic factors cannot be ignored if we wish to fully understand processes that generate marine biodiversity. PMID- 27383819 TI - Visual pigments in a palaeognath bird, the emu Dromaius novaehollandiae: implications for spectral sensitivity and the origin of ultraviolet vision. AB - A comprehensive description of the spectral characteristics of retinal photoreceptors in palaeognaths is lacking. Moreover, controversy exists with respect to the spectral sensitivity of the short-wavelength-sensitive-1 (SWS1) opsin-based visual pigment expressed in one type of single cone: previous microspectrophotometric (MSP) measurements in the ostrich (Struthio camelus) suggested a violet-sensitive (VS) SWS1 pigment, but all palaeognath SWS1 opsin sequences obtained to date (including the ostrich) imply that the visual pigment is ultraviolet-sensitive (UVS). In this study, MSP was used to measure the spectral properties of visual pigments and oil droplets in the retinal photoreceptors of the emu (Dromaius novaehollandiae). Results show that the emu resembles most other bird species in possessing four spectrally distinct single cones, as well as double cones and rods. Four cone and a single rod opsin are expressed, each an orthologue of a previously identified pigment. The SWS1 pigment is clearly UVS (wavelength of maximum absorbance [lambdamax] = 376 nm), with key tuning sites (Phe86 and Cys90) consistent with other vertebrate UVS SWS1 pigments. Palaeognaths would appear, therefore, to have UVS SWS1 pigments. As they are considered to be basal in avian evolution, this suggests that UVS is the most likely ancestral state for birds. The functional significance of a dedicated UVS cone type in the emu is discussed. PMID- 27383821 TI - Evaluating the influence of ventilation and ventilation-compression synchronization on chest compression force and depth during simulated neonatal resuscitation. AB - OBJECTIVES: To investigate the influence of ventilation and ventilation compression synchronization on compression force and sternal displacement during simulated neonatal cardiopulmonary resuscitation (NCPR) on an infant manikin. METHODS: Five Neonatal Resuscitation Program trained clinicians were recruited to perform simulated NCPR on an infant manikin using two-finger (TF) and two-thumb (TT) compression, with synchronous and asynchronous ventilation, as well as without ventilation. The sternal displacement and force were recorded and analyzed. RESULTS: Synchronous ventilation and compression yielded sternal displacements and forces in the range of 22.8-32.4 mm and 15.0-29.8 N, respectively, while asynchronous ventilation and compression produced depths and forces in the range of 21.2-32.4 mm and 14.0-28.8 N, respectively. CONCLUSIONS: Ventilation exerts a significant influence on sternal displacement and force during simulated NCPR, regardless of the compression method used. Ventilation compression synchronization, however, is only significant during TF compression with lower compression forces measured during synchronous ventilation than in asynchronous ventilation. This occurs for two reasons: (i) the strong influence of ventilation forces on the lower magnitude compression forces produced during TF compression relative to TT compression and (ii) in asynchronous ventilation, compression and ventilation may occur simultaneously, with inflation and deflation providing an opposing force to the applied compression force. PMID- 27383820 TI - Colorectal Cancer and Long-Term Exposure to Trihalomethanes in Drinking Water: A Multicenter Case-Control Study in Spain and Italy. AB - BACKGROUND: Evidence on the association between colorectal cancer and exposure to disinfection by-products in drinking water is inconsistent. OBJECTIVES: We assessed long-term exposure to trihalomethanes (THMs), the most prevalent group of chlorination by-products, to evaluate the association with colorectal cancer. METHODS: A multicenter case-control study was conducted in Spain and Italy in 2008-2013. Hospital-based incident cases and population-based (Spain) and hospital-based (Italy) controls were interviewed to ascertain residential histories, type of water consumed in each residence, frequency and duration of showering/bathing, and major recognized risk factors for colorectal cancer. We estimated adjusted odds ratios (OR) for colorectal cancer in association with quartiles of estimated average lifetime THM concentrations in each participant's residential tap water (micrograms/liter; from age 18 to 2 years before the interview) and estimated average lifetime THM ingestion from drinking residential tap water (micrograms/day). RESULTS: We analyzed 2,047 cases and 3,718 controls. Median values (ranges) for average lifetime residential tap water concentrations of total THMs, chloroform, and brominated THMs were 30 (0-174), 17 (0-63), and 9 (0-145) MUg/L, respectively. Total THM concentration in residential tap water was not associated with colorectal cancer (OR = 0.92, 95% CI: 0.66, 1.28 for highest vs. lowest quartile), but chloroform concentrations were inversely associated (OR = 0.31, 95% CI: 0.24, 0.41 for highest vs. lowest quartile). Brominated THM concentrations showed a positive association among men in the highest versus the lowest quartile (OR = 1.43, 95% CI: 0.83, 2.46). Patterns of association were similar for estimated average THM ingestion through residential water consumption. CONCLUSIONS: We did not find clear evidence of an association between detailed estimates of lifetime total THM exposure and colorectal cancer in our large case-control study population. Negative associations with chloroform concentrations and ingestion suggest differences among specific THMs, but these findings should be confirmed in other study populations. Citation: Villanueva CM, Gracia-Lavedan E, Bosetti C, Righi E, Molina AJ, Martin V, Boldo E, Aragones N, Perez-Gomez B, Pollan M, Gomez Acebo I, Altzibar JM, Jimenez Zabala A, Ardanaz E, Peiro R, Tardon A, Chirlaque MD, Tavani A, Polesel J, Serraino D, Pisa F, Castano Vinyals G, Espinosa A, Espejo-Herrera N, Palau M, Moreno V, La Vecchia C, Aggazzotti G, Nieuwenhuijsen MJ, Kogevinas M. 2017. Colorectal cancer and long term exposure to trihalomethanes in drinking water: a multicenter case---control study in Spain and Italy. Environ Health Perspect 125:56-65; http://dx.doi.org/10.1289/EHP155. PMID- 27383822 TI - Urban Telemedicine Enables Equity in Access to Acute Illness Care. AB - BACKGROUND: Children with care for acute illness available through the Health-e Access telemedicine model at childcare and schools were previously found to have 22% less emergency department (ED) use than counterparts without this service, but they also had 24% greater acute care use overall. INTRODUCTION: We assessed the hypothesis that increased utilization reflected improved access among impoverished inner-city children to a level experienced by more affluent suburban children. This observational study compared utilization among children without and with telemedicine access, beginning in 1993, ending in 2007, and based on 84,287 child-months of billing claims-based observation. MATERIALS AND METHODS: Health-e-Access Telemedicine was initiated in stepwise manner over 187 study months among 74 access sites (childcare, schools, community centers), beginning in month 105. Children dwelled in inner city, rest-of-city Rochester, NY, or in surrounding suburbs. Rate of total acute care visits (office, ED, telemedicine) was measured as visits per 100 child-years. Observed utilization rates were adjusted in multivariate analysis for age, sex, insurance type, and season of year. RESULTS: When both suburban and inner-city children lacked telemedicine access, overall acute illness visits were 75% greater among suburban than inner city children (suburban:inner-city rate ratio 1.75, p < 0.0001). After telemedicine became available to inner-city children, their overall acute visits approximated those of suburban children (suburban:inner-city rate ratio 0.80, p = 0.07), whereas acute visits among suburban children remained at least (worst-case comparison) 56% greater than inner-city children without telemedicine (rate ratio 1.56, p < 0.0001). DISCUSSION: At baseline, overall acute illness utilization of suburban children exceeded that of inner-city children. Overall utilization for inner-city children increased with telemedicine to that of suburban children at baseline. Without telemedicine, however, inner-city use remained substantially less than for suburban counterparts. CONCLUSIONS: Health-e-Access Telemedicine redressed socioeconomic disparities in acute care access in the Rochester area, thus contributing to a more equitable community. PMID- 27383823 TI - Empowering Heliotherapy in Psoriasis and Atopic Dermatitis: An Observational Study of 186 Subjects. PMID- 27383824 TI - The association of CYP1A1 genetic polymorphisms and additional gene-gene interaction with ischemic stroke in the eastern Han of China. AB - The aim of this study was to investigate the association between CYP1A1 gene polymorphism and ischaemic stroke (IS) risk, and the impact of gene-gene interaction on IS risk based on a Chinese Han case-control study. A total of 1162 subjects (612 men and 550 women), with a mean age of 63.1 +/- 12.5 years old, were selected, including 580 IS patients and 582 normal controls. Logistic regression was performed to investigate association between single-nucleotide polymorphisms (SNP) and IS risk, and generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene interaction. Logistic regression analysis showed that the frequency for rs4646903 minor alleles was lower in cases than that in normal controls, and C allele of rs4646903 was 20.7 % in ischemic stroke cases and 27.1 % in controls subjects (p < 0.001). Logistic analysis showed the significant association between genotypes of variants in rs4646903 and decreased ischemic stroke risk. GMDR analysis indicated that there was a significant two-locus model (p = 0.0107) involving rs4646903 and rs1048943, indicating a potential gene-gene interaction between rs4646903 and rs1048943. Overall, the two- locus models had a cross-validation consistency of 9 of 10, and had the testing accuracy of 60.72 %. Subjects with TC or CC of rs4646903 and AG or GG of rs1048943 genotype have lowest ischemic stroke risk, compared to subjects with TT of rs4646903 and AA of rs1048943 genotype, and OR (95 % CI) was 0.63 (0.42-0.89). rs4646903 minor alleles and interaction between rs4646903 and rs1048943 were associated with decreased IS risk. PMID- 27383825 TI - Cognitive training for patients with dementia living in a sicilian nursing home: a novel web-based approach. AB - Dementia is an increasing challenge for health care and social system in developed countries. Interventions with a cognitive focus, also using assistive technology, are leading to promising results in improving cognitive and behavior symptoms in individuals with dementia. Aim of our study was to evaluate the combined effects of the standard cognitive training in addition to web-based rehabilitation in dementia people living in a nursing home. We have studied twenty dementia people (10 females and 10 males) with a mild to moderate cognitive decline (MMSE 25 +/- 3.4) associated to moderate behavioral alterations, and mainly due to vascular causes. These patients were randomly assigned to one of two groups (experimental or standard treatment-namely the control group). All participants in the experimental group completed the specific training, consisting of 24 sessions of web-based cognitive training, for 8 weeks, in addition to standard rehabilitation. Each participant was evaluated by a skilled neuropsychologist before and after each treatment. The experimental group had a statistically significant change of the Geriatric Depression Scale (p = 0.03), Constructive Apraxia (p < 0.001), Matrices Attentive (p = 0.01), and Mini Mental State Examination (p = 0.04). Web-based cognitive rehabilitation can be useful in improving cognitive performance, besides psychological well-being, in demented individuals living in home care. PMID- 27383826 TI - Extravascular heroin injection causing neuropathy: ultrasound picture. PMID- 27383827 TI - Response to: The "RACE" national database for recurrent acute rhinosinusitis may need a relook. PMID- 27383828 TI - Persistent neutrophilia is a marker for an increased risk of venous thrombosis. AB - In patients with cancer and myeloproliferative disorders, leukocytosis has been associated with an increased venous thromboembolic (VTE) risk. Our goal was to determine whether persistent neutrophilia (PN), not associated with known causes such as malignancies, infections or steroids, is independently associated with VTE. All adult patients with >3 outpatient complete blood counts (CBCs) within 3 years were included. PN was defined as having an absolute neutrophil count >95 % (>2SD) of the population (>=7.8 * 10(9)/L) on at least three CBCs, at least 2 months apart. Separate analyses for neutrophil counts >=9 * 10(9)/L and >=10 * 10(9)/L were also performed. Blood counts from inpatients were excluded. Primary outcome was diagnosis of VTE, as determined by ICD-9 codes. Odds ratios were adjusted for diabetes, smoking, obesity, gender, and age. Charlson score was utilized as a morbidity measure. Data on 43,538 outpatients were collected. Although there was no association of VTE with neutrophil counts >=7.8 * 10(9)/L, patients with >=9.0 * 10(9)/L neutrophils were twice as likely to be diagnosed with VTE compared to those with normal neutrophil counts (OR 2.0, 95 % CI 1.3, 3.1; p = 0.003). Patients with neutrophil counts >=10.0 * 10(9)/L were at an even higher risk (OR 2.3, 95 % CI 1.2, 4.8; p = 0.019). Charlson scores significantly modified this risk when incorporated into analysis. Elevated neutrophil counts are associated with an increased risk of venous thrombosis even when they are not due to cancer, infection or steroids. In patients with significant comorbidities, neutrophilia may be a marker of VTE risk. PMID- 27383830 TI - B7-H4 expression indicates poor prognosis of oral squamous cell carcinoma. AB - Checkpoint blockade therapy utilizing monoclonal antibodies to reactivate T cells and recover their antitumor activity makes an epoch in cancer immunotherapy. The role of B7-H4, a novel negative immune checkpoint, in oral squamous cell carcinoma (OSCC) has still not been elucidated. In this study, tissue samples from human OSCC, which contains 165 primary OSCC, 48 oral epithelial dysplasia and 43 normal oral mucosa specimens, and Tgfbr1/Pten 2cKO mice OSCC model were stained with B7-H4 antibody to analyze the correlations between B7-H4 expression and clinicopathological characteristics. Kaplan-Meier analysis was used to compare the survival of patients with high B7-H4 expression and patients with low B7-H4 expression. We found B7-H4 is highly expressed in human OSCC tissue, and the B7-H4 expression level was associated with the clinicopathological parameters containing pathological grade and lymph node status. Moreover, we confirmed that B7-H4 was overexpressed in Tgfbr1/Pten 2cKO mice OSCC model. Our data also indicated that patients with high B7-H4 expression had poor overall survival compared with those with low B7-H4 expression. Furthermore, this study demonstrated that B7-H4 was positively associated with PD-L1, CD11b, CD33, PI3Kalpha p110, and p-S6 (S235/236). Taken together, these findings suggest B7-H4 is a potential target in the treatment of OSCC. PMID- 27383829 TI - Asymmetric Cancer Hallmarks in Breast Tumors on Different Sides of the Body. AB - During the last decades it has been established that breast cancer arises through the accumulation of genetic and epigenetic alterations in different cancer related genes. These alterations confer the tumor oncogenic abilities, which can be resumed as cancer hallmarks (CH). The purpose of this study was to establish the methylation profile of CpG sites located in cancer genes in breast tumors so as to infer their potential impact on 6 CH: i.e. sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, induction of angiogenesis, genome instability and invasion and metastasis. For 51 breast carcinomas, MS-MLPA derived-methylation profiles of 81 CpG sites were converted into 6 CH profiles. CH profiles distribution was tested by different statistical methods and correlated with clinical-pathological data. Unsupervised Hierarchical Cluster Analysis revealed that CH profiles segregate in two main groups (bootstrapping 90-100%), which correlate with breast laterality (p = 0.05). For validating these observations, gene expression data was obtained by RealTime-PCR in a different cohort of 25 tumors and converted into CH profiles. This analyses confirmed the same clustering and a tendency of association with breast laterality (p = 0.15). In silico analyses on gene expression data from TCGA Breast dataset from left and right breast tumors showed that they differed significantly when data was previously converted into CH profiles (p = 0.033). We show here for the first time, that breast carcinomas arising on different sides of the body present differential cancer traits inferred from methylation and expression profiles. Our results indicate that by converting methylation or expression profiles in terms of Cancer Hallmarks, it would allow to uncover veiled associations with clinical features. These results contribute with a new finding to the better understanding of breast tumor behavior, and can moreover serve as proof of principle for other bilateral cancers like lung, testes or kidney. PMID- 27383832 TI - Role of farnesoid X receptor in cholestasis. AB - The nuclear receptor farnesoid X receptor (FXR) plays an important role in physiological bile acid synthesis, secretion and transport. Defects of FXR regulation in these processes can cause cholestasis and subsequent pathological changes. FXR regulates the synthesis and uptake of bile acid via enzymes. It also increases bile acid solubility and elimination by promoting conjugation reactions and exports pump expression in cholestasis. The changes in bile acid transporters are involved in cholestasis, which can result from the mutations of transporter genes or acquired dysfunction of transport systems, such as inflammation-induced intrahepatic cholestasis. The modulation function of FXR in extrahepatic cholestasis is not identical to that in intrahepatic cholestasis, but the discrepancy may be reduced over time. In extrahepatic cholestasis, increasing biliary pressure can induce bile duct proliferation and bile infarcts, but the absence of FXR may ameliorate them. This review provides an update on the function of FXR in the regulation of bile acid metabolism, its role in the pathophysiological process of cholestasis and the therapeutic use of FXR agonists. PMID- 27383831 TI - Delineation of six species of the primitive algal genus Glaucocystis based on in situ ultrastructural characteristics. AB - The field of microbiology was established in the 17(th) century upon the discovery of microorganisms by Antonie van Leeuwenhoek using a single-lens microscope. Now, the detailed ultrastructures of microorganisms can be elucidated in situ using three-dimensional electron microscopy. Since the availability of electron microscopy, the taxonomy of microscopic organisms has entered a new era. Here, we established a new taxonomic system of the primitive algal genus Glaucocystis (Glaucophyta) using a new-generation electron microscopic methodology: ultra-high-voltage electron microscopy (UHVEM) and field-emission scanning electron microscopy (FE-SEM). Various globally distributed Glaucocystis strains were delineated into six species, based on differences in in situ ultrastructural features of the protoplast periphery under UHVEM tomography and in the mother cell wall by FE-SEM, as well as differences in the light microscopic characteristics and molecular phylogenetic results. The present work on Glaucocystis provides a model case of new-generation taxonomy. PMID- 27383833 TI - Optic-null space medium for cover-up cloaking without any negative refraction index materials. AB - With the help of optic-null medium, we propose a new way to achieve invisibility by covering up the scattering without using any negative refraction index materials. Compared with previous methods to achieve invisibility, the function of our cloak is to cover up the scattering of the objects to be concealed by a background object of strong scattering. The concealed object can receive information from the outside world without being detected. Numerical simulations verify the performance of our cloak. The proposed method will be a great addition to existing invisibility technology. PMID- 27383834 TI - Positive Predictive Value of the WHO Clinical and Immunologic Criteria to Predict Viral Load Failure among Adults on First, or Second-Line Antiretroviral Therapy in Kenya. AB - Routine HIV viral load (VL) monitoring is the standard of care for persons receiving antiretroviral therapy (ART) in developed countries. Although the World Health Organization recommends annual VL monitoring of patients on ART, recognizing difficulties in conducting routine VL testing, the WHO continues to recommend targeted VL testing to confirm treatment failure for persons who meet selected immunologic and clinical criteria. Studies have measured positive predictive value (PPV), negative predictive value, sensitivity and specificity of these criteria among patients receiving first-line ART but not specifically among those on second-line or subsequent regimens. Between 2008 and 2011, adult ART patients in Nyanza, Kenya who met national clinical or immunologic criteria for treatment failure received targeted VL testing. We calculated PPV and 95% confidence intervals (CI) of these criteria to detect virologic treatment failure among patients receiving a) first-line ART, b) second/subsequent ART, and c) any regimen. Of 12,134 patient specimens tested, 2,874 (23.7%) were virologically confirmed as treatment failures. The PPV for 2,834 first-line ART patients who met either the clinical or immunologic criteria for treatment failure was 34.4% (95% CI 33.2-35.7), 33.1% (95% CI 24.7-42.3) for the 40 patients on second line/subsequent regimens, and 33.4% (95% CI 33.1-35.6) for any ART. PPV, regardless of criteria, for first-line ART patients was lowest among patients over 44 years old and highest for patients aged 15 to 34 years. PPV of immunological and clinical criteria for correctly identifying treatment failure was similarly low for adult patients receiving either first-line or second line/subsequent ART regimens. Our data confirm the inadequacy of clinical and immunologic criteria to correctly identify treatment failure and support the implementation of routine VL testing. PMID- 27383835 TI - Hip osteoarthritis. PMID- 27383836 TI - Marginal Micronutrient Intake in High-Performance Male Wheelchair Basketball Players: A Dietary Evaluation and the Effects of Nutritional Advice. AB - Wheelchair basketball has evolved into a high-performance sport over several years, and small variations in player performance can determine the difference between winning and losing. Therefore, adequate micronutrient intake may influence this difference if performance-promoting macronutrient intake and physical fitness are equal between teams. Seventeen elite male wheelchair basketball players belonging to the Spanish National Team participated in this study. Macro- and micronutrient intake were determined using a food-weighing diary over three consecutive days during three training camps in two consecutive years. Current Dietary Reference Intake levels were used to determine the adequacy of intake of seventeen micronutrients of particular interest for athletes. After categorizing the consumed foods into fourteen food groups according to the National Nutrient Database for Standard References (USDA) these groups were used to identify the best predictors of the adequacy of intake for each micronutrient. Total energy intake correlated positively with the adequacy of all micronutrient intake levels, except for vitamins A and E. Five B vitamins and phosphorus, selenium, and iron showed 100% adequacy. All other micronutrient intake levels were found to be inadequate, e.g., vitamin E (51% adequacy) and calcium (73%). The fruit, fish and cereal food groups were found to be predictors of adequate intake of most micronutrients. Together with energy intake (p = .009, eta2 = 0.49), the intake of the fruit (p = .032, eta2 = 0.39) and egg (p = .036, Kendall's W = 0.42) food groups increased significantly over time, along with improved iodine (p = .008, W = 0.61) and magnesium (p = .030, W = 0.44) adequacy levels. Because the adequacy of micronutrient intake correlates positively with energy intake (R = 0.64, p < .001), a varied diet that includes cereals, fish and fruits is especially important for players with low levels of energy intake. Supplements may be a possible solution if adequate micronutrient intake cannot be achieved through regular dietary intake alone. However, dietary analyses should be conducted on a regular basis throughout the year to improve the nutritional knowledge of the athletes and assure adequate micronutrient intake. PMID- 27383837 TI - Circulating Extracellular Vesicles Contain miRNAs and are Released as Early Biomarkers for Cardiac Injury. AB - Plasma-circulating microRNAs have been implicated as novel early biomarkers for myocardial infarction (MI) due to their high specificity for cardiac injury. For swift clinical translation of this potential biomarker, it is important to understand their temporal and spatial characteristics upon MI. Therefore, we studied the temporal release, potential source, and transportation of circulating miRNAs in different models of ischemia reperfusion (I/R) injury. We demonstrated that extracellular vesicles are released from the ischemic myocardium upon I/R injury. Moreover, we provided evidence that cardiac and muscle-specific miRNAs are transported by extracellular vesicles and are rapidly detectable in plasma. Since these vesicles are enriched for the released miRNAs and their detection precedes traditional damage markers, they hold great potential as specific early biomarkers for MI. PMID- 27383838 TI - Evidence for the Participation of Acid-Sensing Ion Channels (ASICs) in the Antinociceptive Effect of Curcumin in a Formalin-Induced Orofacial Inflammatory Model. AB - Curcumin, a major bioactive component of turmeric, has diverse therapeutic effects such as anti-inflammatory, antioxidant, anticancer, and antinociceptive activities. The acid-sensing ion channels (ASICs), which can be activated by acute drops in the extracellular pH, play an important role in nociception. However, very little is known about the interaction between ASICs and curcumin in nociception of inflammation. In our study, we investigated whether the antinociceptive effects of curcumin are mediated via ASICs using an orofacial nociceptive model and in vitro western blotting, immunofluorescence, whole-cell patch-clamp recordings in the trigeminal system. Intraperitoneally administered curcumin at a dose of 50 mg/kg can reduce hyperalgesia in both the phases of a formalin-induced orofacial nociceptive model. Curcumin reduced the amplitude of ASICs currents in a dose-dependent manner in trigeminal ganglion (TG) neurons, and curcumin also reduced the protein quantity but did not change the distribution of ASICs in TG. Thus, our results indicate that curcumin can reduce formalin-induced ASICs activation and thus inhibit ASICs-mediated inflammatory pain hypersensitivity. PMID- 27383840 TI - External radiation dose and cancer mortality among French nuclear workers: considering potential confounding by internal radiation exposure. AB - OBJECTIVES: French nuclear workers have detailed records of their occupational exposure to external radiation that have been used to examine associations with subsequent cancer mortality. However, some workers were also exposed to internal contamination by radionuclides. This study aims to assess the potential for bias due to confounding by internal contamination of estimates of associations between external radiation exposure and cancer mortality. METHODS: A cohort of 59,004 workers employed for at least 1 year between 1950 and 1994 by CEA (Commissariat a l'Energie Atomique), AREVA NC, or EDF (Electricite de France) and badge-monitored for external radiation exposure were followed through 2004 to assess vital status and cause of death. A flag based on a workstation-exposure matrix defined four levels of potential for internal contamination. Standardized mortality ratios were assessed for each level of the internal contamination indicator. Poisson regression was used to quantify associations between external radiation exposure and cancer mortality, adjusting for potential internal contamination. RESULTS: For solid cancer, the mortality deficit tended to decrease as the levels of potential for internal contamination increased. For solid cancer and leukemia excluding chronic lymphocytic leukemia, adjusting the dose-response analysis on the internal contamination indicator did not markedly change the excess relative risk per Sievert of external radiation dose. CONCLUSIONS: This study suggests that in this cohort, neglecting information on internal dosimetry while studying the association between external dose and cancer mortality does not generate a substantial bias. To investigate more specifically the health effects of internal contamination, an effort is underway to estimate organ doses due to internal contamination. PMID- 27383841 TI - Predicting Hybrid Performances for Quality Traits through Genomic-Assisted Approaches in Central European Wheat. AB - Bread-making quality traits are central targets for wheat breeding. The objectives of our study were to (1) examine the presence of major effect QTLs for quality traits in a Central European elite wheat population, (2) explore the optimal strategy for predicting the hybrid performance for wheat quality traits, and (3) investigate the effects of marker density and the composition and size of the training population on the accuracy of prediction of hybrid performance. In total 135 inbred lines of Central European bread wheat (Triticum aestivum L.) and 1,604 hybrids derived from them were evaluated for seven quality traits in up to six environments. The 135 parental lines were genotyped using a 90k single nucleotide polymorphism array. Genome-wide association mapping initially suggested presence of several quantitative trait loci (QTLs), but cross validation rather indicated the absence of major effect QTLs for all quality traits except of 1000-kernel weight. Genomic selection substantially outperformed marker-assisted selection in predicting hybrid performance. A resampling study revealed that increasing the effective population size in the estimation set of hybrids is relevant to boost the accuracy of prediction for an unrelated test population. PMID- 27383842 TI - Association between violence exposure and condom non-use among transgender sex workers in the Dominican Republic: the mediating role of trust. AB - Transgender women are a high-risk population, and transgender female sex workers are one of the most vulnerable populations globally. Transgender female sex workers have high rates of sexually transmitted infections, HIV, and exposure to violence compared to cisgender sex workers; these negative exposures are associated with an increase in HIV risk behaviors. Thus, the aim of this study is to examine the relationship between exposure to violence and condom non-use in transgender female sex workers residing in the Dominican Republic. We hypothesize that mediation exists wherein the effects of violence on condom non-use are mediated by distrust. Facilitated interview data ( N = 78) were used. Primary outcome was condom non-use with coercive partner. Four logistic regression models and a mediation analysis were employed. Respondents' mean age was 23.0 years (SD = 4.8) with an average level education attainment of 10.1 years (SD = 2.6); 35% reported experiencing violence; 17% believed that a person who asks a partner to use a condom does not trust that partner. Exploratory mediation analyses yielded a significant indirect effect of experience with violence on condom non-use through distrust (b = 0.64, SE = 0.33, p = .05). Results suggest that distrust mediates the association between experienced violence and condom use with coercive partners. It was concluded that developing interventions on increasing resilience and perceived self-worth, plus provision of screening for violence and referral services may reduce maladaptive attributions and cognitions about condom use. Furthermore, by implementing policies that protect vulnerable populations, and subsequently enforcing them, the Dominican Republic has the opportunity to improve overall population health and protect their most disadvantaged citizens. PMID- 27383839 TI - Pathophysiology Associated with Traumatic Brain Injury: Current Treatments and Potential Novel Therapeutics. AB - Traumatic brain injury (TBI) is one of the leading causes of death of young people in the developed world. In the United States alone, 1.7 million traumatic events occur annually accounting for 50,000 deaths. The etiology of TBI includes traffic accidents, falls, gunshot wounds, sports, and combat-related events. TBI severity ranges from mild to severe. TBI can induce subtle changes in molecular signaling, alterations in cellular structure and function, and/or primary tissue injury, such as contusion, hemorrhage, and diffuse axonal injury. TBI results in blood-brain barrier (BBB) damage and leakage, which allows for increased extravasation of immune cells (i.e., increased neuroinflammation). BBB dysfunction and impaired homeostasis contribute to secondary injury that occurs from hours to days to months after the initial trauma. This delayed nature of the secondary injury suggests a potential therapeutic window. The focus of this article is on the (1) pathophysiology of TBI and (2) potential therapies that include biologics (stem cells, gene therapy, peptides), pharmacological (anti inflammatory, antiepileptic, progrowth), and noninvasive (exercise, transcranial magnetic stimulation). In final, the review briefly discusses membrane/lipid rafts (MLR) and the MLR-associated protein caveolin (Cav). Interventions that increase Cav-1, MLR formation, and MLR recruitment of growth-promoting signaling components may augment the efficacy of pharmacologic agents or already existing endogenous neurotransmitters and neurotrophins that converge upon progrowth signaling cascades resulting in improved neuronal function after injury. PMID- 27383843 TI - Birds of a Feather: Social Bases of Neighborhood Formation in Newark, New Jersey, 1880. AB - This study examines the bases of residential segregation in a late nineteenth century American city, recognizing the strong tendency toward homophily within neighborhoods. Our primary question is how ethnicity, social class, nativity, and family composition affect where people live. Segregation is usually studied one dimension at a time, but these social differences are interrelated, and thus a multivariate approach is needed to understand their effects. We find that ethnicity is the main basis of local residential sorting, while occupational standing and, to a lesser degree, family life cycle and nativity also are significant. A second concern is the geographic scale of neighborhoods: in this study, the geographic area within which the characteristics of potential neighbors matter in locational outcomes of individuals. Studies of segregation typically use a single spatial scale, often one determined by the availability of administrative data. We take advantage of a unique data set containing the address and geo-referenced location of every resident. We conclude that it is the most local scale that offers the best prediction of people's similarity to their neighbors. Adding information at larger scales minimally improves prediction of the person's location. The 1880 neighborhoods of Newark, New Jersey, were formed as individuals located themselves among similar neighbors on a single street segment. PMID- 27383844 TI - Same-Sex and Different-Sex Cohabiting Couple Relationship Stability. AB - Relationship stability is a key indicator of well-being, but most U.S.-based research has been limited to different-sex couples. The 2008 panel of the Survey of Income and Program Participation (SIPP) provides an untapped data resource to analyze relationship stability of same-sex cohabiting, different-sex cohabiting, and different-sex married couples (n = 5,701). The advantages of the SIPP data include the recent, nationally representative, and longitudinal data collection; a large sample of same-sex cohabitors; respondent and partner socioeconomic characteristics; and identification of a state-level indicator of a policy stating that marriage is between one man and one woman (i.e., DOMA). We tested competing hypotheses about the stability of same-sex versus different-sex cohabiting couples that were guided by incomplete institutionalization, minority stress, relationship investments, and couple homogamy perspectives (predicting that same-sex couples would be less stable) as well as economic resources (predicting that same-sex couples would be more stable). In fact, neither expectation was supported: results indicated that same-sex cohabiting couples typically experience levels of stability that are similar to those of different sex cohabiting couples. We also found evidence of contextual effects: living in a state with a constitutional ban against same-sex marriage was significantly associated with higher levels of instability for same- and different-sex cohabiting couples. The level of stability in both same-sex and different-sex cohabiting couples is not on par with that of different-sex married couples. The findings contribute to a growing literature on health and well-being of same-sex couples and provide a broader understanding of family life. PMID- 27383845 TI - Life Expectancy Among U.S.-born and Foreign-born Older Adults in the United States: Estimates From Linked Social Security and Medicare Data. AB - In recent decades, the geographic origins of America's foreign-born population have become increasingly diverse. The sending countries of the U.S. foreign-born vary substantially in levels of health and economic development, and immigrants have arrived with distinct distributions of socioeconomic status, visa type, year of immigration, and age at immigration. We use high-quality linked Social Security and Medicare records to estimate life tables for the older U.S. population over the full range of birth regions. In 2000-2009, the foreign-born had a 2.4-year advantage in life expectancy at age 65 relative to the U.S.-born, with Asian-born subgroups displaying exceptionally high longevity. Foreign-born individuals who migrated more recently had lower mortality compared with those who migrated earlier. Nonetheless, we also find remarkable similarities in life expectancy among many foreign-born subgroups that were born in very different geographic and socioeconomic contexts (e.g., Central America, western/eastern Europe, and Africa). PMID- 27383846 TI - Population Policy: Abortion and Modern Contraception Are Substitutes. AB - A longstanding debate exists in population policy about the relationship between modern contraception and abortion. Although theory predicts that they should be substitutes, the empirical evidence is difficult to interpret. What is required is a large-scale intervention that alters the supply (or full price) of one or the other and, importantly, that does so in isolation (reproductive health programs often bundle primary health care and family planning-and in some instances, abortion services). In this article, we study Nepal's 2004 legalization of abortion provision and subsequent expansion of abortion services, an unusual and rapidly implemented policy meeting these requirements. Using four waves of rich individual-level data representative of fertile-age Nepalese women, we find robust evidence of substitution between modern contraception and abortion. This finding has important implications for public policy and foreign aid, suggesting that an effective strategy for reducing expensive and potentially unsafe abortions may be to expand the supply of modern contraceptives. PMID- 27383847 TI - Terminalia Chebulanin Attenuates Psoriatic Skin Lesion via Regulation of Heme Oxygenase-1. AB - BACKGROUND/AIMS: Psoriasis is one of the most common inflammatory skin disorders, affecting 3% of the general population. Terminalia chebulanin (TC) is a polyphenolic compound that possesses antioxidant and anti-inflammatory activities. The current study was designed to investigate the effect of TC on psoriatic lesions. METHODS: We examined the protective effect of TC against psoriatic lesions in mice and keratinocyte proliferation in HaCaT cells. RESULTS: We found that TC exhibited potent anti-psoriatic activities, as evidenced by improvement of erythema and scaling scores, decrease of epidermal, ear and skinfold thickening, decrease of tumor necrosis factor alpha (TNFalpha), interleukin (IL)-17A, IL-23 and matrix metalloproteinase (MMP)-9 expression, and decrease of TBARS content and increase of GSH content in IMQ-treated mice, and decrease of keratinocyte proliferation, TNFalpha, IL-17A and IL-23 expression, and ROS level in M5-treated cells. All those effects induced by TC were inhibited by zinc protoporphyrin IX (ZnPP), an inhibitor of heme oxygenase (HO)-1, indicating that HO-1 was responsible the anti-psoriatic effect of TC. Moreover, TC inhibited the upregulation of p65 NF-x03BA;B under in vitro psoriatic condition. ZnPP suppressed TC-induced inhibition of p65 NF-x03BA;B expression. Overexpression of p65 NF-x03BA;B significantly suppressed TC-induced decrease of TNFalpha, IL-17A and IL-23 expression and keratinocyte proliferation, indicating that HO-1-mediated downregulation of NF-x03BA;B was involved in the anti psoriatic effect of TC. CONCLUSIONS: The data demonstrate that TC may serve as a potential therapeutic option for psoriatic patients. PMID- 27383848 TI - Quality of life in Chinese family caregivers for elderly people with chronic diseases. AB - BACKGROUND: Inadequate studies have been conducted in China to examine quality of life in family caregivers. Quality of life in family caregivers for elderly people with chronic diseases was evaluated, and the demographic and characteristic factors of both elderly people and their caregivers were explored. METHODS: The 36-Item Short Form Health Survey (SF-36) was used to assess health related quality of life in 407 family caregivers caring for elderly people with chronic diseases in six communities on the Mainland China. The explanatory variables included family caregivers' demographic and other caregiving variables related to eldercare. Descriptive statistics and multiple linear regression analysis were used in the data analysis, performed via SPSS 17.0. RESULTS: Mean SF-36 and physical and mental component scores were 66.14 +/- 17.50, 70.06 +/- 16.49, and 62.22 +/- 18.51, respectively. The scores of caregivers' physical function and bodily pain were significantly higher, while the scores of caregivers' role limitations due to physical problems, general health, vitality, social function, mental health and role limitations due to emotional problems were significantly lower. Caregivers' ages, comorbidity, the perceived effects of caregiving on caregivers' social lives and elderly individuals' ages, marital status and Activities of Daily Living scores were significantly associated with the physical component score. In addition, caregivers' age, the affordability of the elderly person's healthcare expenses, the perceived effects of caregiving on caregivers' social lives, and elderly people's marital status and ADL scores were significantly associated with the mental component score. CONCLUSION: Family caregivers for elderly people with chronic diseases showed poorer mental and better physical well-being. Factors of both elderly people and their caregivers impact the caregivers' quality of life. These findings highlight the importance of addressing mental health of family caregivers, and of providing economical support and psychological care for them. PMID- 27383849 TI - Polyethylene glycol grafted flower-like cupric nano oxide for the hollow-fiber solid-phase microextraction of hexaconazole, penconazole, and diniconazole in vegetable samples. AB - A simple, rapid, highly efficient, and reliable sample preparation method has been developed for the extraction and analysis of triazole pesticides from cucumber, lettuce, bell pepper, cabbage, and tomato samples. This new sorbent in the hollow-fiber solid-phase microextraction method is based on the synthesis of polyethylene glycol-polyethylene glycol grafted flower-like cupric oxide nanoparticles using sol-gel technology. Afterward, the analytes were analyzed by high-performance liquid chromatography with ultraviolet detection. The main parameters that affect microextraction efficiency were evaluated and optimized. This method has afforded good linearity ranges (0.5-50 000 ng/mL for hexaconazol, 0.012-50 000 ng/mL for penconazol, and 0.02-50 000 ng/mL for diniconazol), adequate precision (2.9-6.17%, n = 3), batch-to-batch reproducibility (4.33 8.12%), and low instrumental LODs between 0.003 and 0.097 ng/mL (n = 8). Recoveries and enrichment factors were 85.46-97.47 and 751-1312%, respectively. PMID- 27383851 TI - Rapid Assessment of Resistance to Antibiotic Inhibitors of Protein Synthesis in the Gram-Positive Pathogens, Enterococcus faecalis and Streptococcus pneumoniae, Based on Evaluation of the Lytic Response. AB - A novel assay for rapid determination of resistance to antibiotic inhibitors of protein synthesis was developed for the gram-positive pathogens, Enterococcus faecalis and Streptococcus pneumoniae. To this purpose, a lytic response was obtained by a brief incubation with lysozyme or a mixture of lysozyme, Triton X 100, and EDTA for E. faecalis (n = 82) and S. pneumoniae (n = 51), respectively. Lysis was quantified by visualizing the released nucleoids. Antibiotic susceptible bacteria treated with Clinical and Laboratory Standards Institute (CLSI) breakpoint doses of erythromycin, azithromycin, or doxycycline that inhibited protein synthesis demonstrated a large reduction of lysed cells with respect to the control, that is, without antibiotics. However, cell lysis prevention was much lower in nonsusceptible strains, with unsuccessful inhibition of protein synthesis. ROC analysis showed that a reduction value of >=35.6% and >=40.4% discriminates susceptible and nonsusceptible strains for erythromycin and for doxycycline, respectively, in E. faecalis, whereas >=20.0% is adequate for both macrolides and doxycycline in S. pneumoniae. Resistant stains were identified in 90-120 min with sensitivity and specificity between 91.7% and 100%. This is a proof of concept that evaluation of the lytic response may be a rapid and efficient test for determination of resistance to antibiotic inhibitors of protein synthesis. PMID- 27383852 TI - An Emergency Department Presentation of Erythema Ab Igne Caused by Repeated Heater Exposure. AB - Erythema ab igne is a rare, reticular erythematous hyperpigmentation resulting from repeated thermal injury. We describe our assessment of a 22-year-old woman with bilateral shin discoloration of 3 weeks' duration. Upon questioning, she revealed that she had been standing near a portable heater for extended periods. She was advised to avoid further exposure to the heat source. By the time of a follow-up clinic visit, the discoloration had resolved. Patients with hyperpigmented patches should be questioned about heat exposure. Erythema ab igne can progress to serious dermatologic conditions, but if the cause is eliminated, it usually resolves without medical intervention. PMID- 27383850 TI - Identification of BECN1 and ATG14 Coiled-Coil Interface Residues That Are Important for Starvation-Induced Autophagy. AB - Autophagy, an essential eukaryotic homeostasis pathway, allows the sequestration of unwanted, damaged, or harmful cytoplasmic components in vesicles called autophagosomes, permitting subsequent lysosomal degradation and nutrient recycling. Autophagosome nucleation is mediated by class III phosphatidylinositol 3-kinase complexes that include two key autophagy proteins, BECN1/Beclin 1 and ATG14/BARKOR, which form parallel heterodimers via their coiled-coil domains (CCDs). Here we present the 1.46 A X-ray crystal structure of the antiparallel, human BECN1 CCD homodimer, which represents BECN1 oligomerization outside the autophagosome nucleation complex. We use circular dichroism and small-angle X-ray scattering (SAXS) to show that the ATG14 CCD is significantly disordered but becomes more helical in the BECN1:ATG14 heterodimer, although it is less well folded than the BECN1 CCD homodimer. SAXS also indicates that the BECN1:ATG14 heterodimer is more curved than other BECN1-containing CCD dimers, which has important implications for the structure of the autophagosome nucleation complex. A model of the BECN1:ATG14 CCD heterodimer that agrees well with the SAXS data shows that BECN1 residues at the homodimer interface are also responsible for heterodimerization, allowing us to identify ATG14 interface residues. Finally, we verify the role of BECN1 and ATG14 interface residues in binding by assessing the impact of point mutations of these residues on co-immunoprecipitation of the partner and demonstrate that these mutations abrogate starvation-induced upregulation of autophagy but do not impact basal autophagy. Thus, this research provides insights into structures of the BECN1 CCD homodimer and the BECN1:ATG14 CCD heterodimer and identifies interface residues that are important for BECN1:ATG14 heterodimerization and for autophagy. PMID- 27383853 TI - Missed Opportunities for Health Promotion Intervention in the Management of Alcohol Withdrawal Syndrome. AB - OBJECTIVE: We aimed to characterize utilization of evidence-based health promotion practices not included in Alcohol Withdrawal Syndrome (AWS) guidelines, such as vaccinations and counseling services, hypothesizing that missed opportunities for health promotion intervention would abound. METHODS: Retrospective medical record review of 99 patients presenting to a safety-net academic medical center with AWS between August 1, 2012 and March 31, 2013. RESULTS: Thiamine replacement (70%), tobacco cessation counseling (28%), influenza or pneumonia vaccination (25% and 28% respectively), psychiatric counseling (70%), referral to alcohol support group or treatment center(40%), and screening for viral hepatitis and HIV (39% and 44%, respectively) were documented by healthcare providers at lower than optimal frequency. CONCLUSIONS: Provision of health promotion interventions was not consistent with evidence-based practices. Integration of these measures into AWS protocols and guidelines could help clinicians provide consistent, cost-effective, evidence- based care. PMID- 27383854 TI - Retroperitoneal Hematoma Causing Peritoneal Dialysis Catheter Malfunction. AB - BACKGROUND: We present the unusual complication of peritoneal dialysis (PD) catheter dysfunction in a patient who developed a retroperitoneal hematoma following an endoscopic procedure and review the existing literature regarding this rare complication. CASE REPORT: A 60-year-old man with end stage renal disease presented with PD catheter dysfunction. Computed tomography scan of his abdomen showed a large left retroperitoneal hematoma. He underwent a diagnostic laparoscopy and PD catheter revision. The retroperitoneal hematoma had ruptured into the peritoneum with clots clogging the catheter. Clots were evacuated and the catheter was flushed. He restarted on low volume PD three days after surgery and increased to full volume within a week with no further issues. CONCLUSIONS: This case summarizes the very unusual complication of a retroperitoneal bleed from an endoscopic procedure that manifested as PD catheter dysfunction. The increasing utilization of PD catheters requires that surgeons remain aware of potential complications. PMID- 27383855 TI - Tickborne Coinfections in the United States. AB - Unlike mosquitoes, ticks transmit the broadest range of pathogens, including bacteria, viruses, and parasites. Ticks have capitalized on many competitive advantages offered to them by changes in climate and human lifestyle and a greater abundance of wild animal reservoir hosts no longer effectively controlled. As a result, tick-transmitted coinfections are increasing today with both recognized and newly discovered pathogens that complicate differential diagnosis and antimicrobial treatment. Without the support of immunological and molecular diagnostic techniques, usually only available at federal and some state laboratories, the initial differential diagnosis of tickborne coinfections is complicated and antimicrobial therapy may not cover coinfections. Therefore, the objectives of this review were to identify the newly emerging tickborne pathogens in the United States, to describe the evolving epidemiology of tick-transmitted coinfections, to design a decision tree analysis approach to the clinical diagnosis and management of tickborne coinfections, and to recommend effective strategies for the control and personal prevention of tickborne diseases. Clinicians should suspect tickborne coinfections in returning travelers and vacationers with clinical and immunological evidence of multiple infecting agents, especially in cases of unusual presentation or severity, prolonged duration, or nonresponse to single antibiotic therapy, typically with doxycycline. Decision tree models based on pathogen prevalence rates in ticks and their zoonotic reservoirs may assist clinicians in diagnosing tickborne coinfections and guiding initial antimicrobial therapy. PMID- 27383856 TI - Traumatic Presentation of a Periorbital Dermoid Cyst: A Case Report. AB - Dermoid cysts are largely considered benign, developmental neoplasms that frequently present during childhood. Orbitofacial dermoids represent a unique group of embryologically derived soft tissue masses that often present as localized, well-circumscribed swellings along the embryonal suture lines. Clinical presentation is variable, but in rare instances, may be preceded by local trauma, possibly suggesting an inciting event as the initial stimulus to cyst enlargement. Although dermoid cysts tend to remain clinically benign, their natural history of gradual enlargement necessitates complete surgical excision to prevent complications. PMID- 27383857 TI - WUnicuspid Aortic Valve- An Uncommon Anomaly With a Common Presentation. AB - Unicuspid aortic valve (UAV), which is a rare congenital anomaly, usually presents as aortic stenosis and/or aortic regurgitation. Here we present a case of UAV co-existent with an ascending aortic aneurysm. A 26-year-old male with no significant past medical history presented to the hospital after two episodes of syncope. Transthoracic echocardiogram showed an ejection fraction of 62%, severely stenotic aortic valve, and moderate aortic regurgitation. Computed tomography revealed calcification of the aortic valve, compatible with aortic stenosis and aneurysm of the ascending aorta measuring 4.3 cm in diameter. He underwent successful aortic valve replacement and repair of ascending aortic aneurysm. He recovered well without any complications. This case suggests that any young patient who presents with syncope, aortic stenosis would be a differential and further workup by any available non-invasive modality needs to be performed. PMID- 27383858 TI - Wegener's Granulomatosis Presenting as a Parapharyngeal Mass. AB - BACKGROUND: Wegener's Granulomatosis (WG) is classically characterized by the triad of sinonasal, pulmonary, and renal manifestations. However, a growing body of research has demonstrated that atypical head and neck pathologies including retropharyngeal and parapharyngeal lesions are often the presenting feature of patients found to have WG. CASE: This report describes the hospital course of a patient who presented with a parapharyngeal mass with secondary superior cervical chain compression and Lemierre's Syndrome. We discuss how a stepwise approach involving a multidisciplinary team led to the diagnosis of WG. CONCLUSIONS: To our knowledge, this report is the first description of a patient presenting with a parapharyngeal mass causing superior cervical chain compression with simultaneous Lemierre's Syndrome who was ultimately diagnosed with WG. We highlight how the early consideration of WG in patients with atypical head and neck lesions refractory to multiple treatment regimens can led to an expeditious diagnosis and the coordination of appropriate short-term and long-term care. PMID- 27383859 TI - Clinical Case of the Month: A 56-Year-Old Man with Sudden Onset Abdominal Pain. AB - Acute abdominal pain is one of the most common presentations encountered in the emergency department (ED). The differential diagnosis of acute abdominal pain is extensive and identifying the underlying etiology can be challenging. Spontaneous renal artery thrombosis is a rare cause of acute abdominal pain. We review a case of acute presentation of renal artery thrombosis in a patient without risk factors for thromboembolism, and highlight the importance of considering this rare cause of abdominal pain. PMID- 27383860 TI - ECG Of the Month: Suicide. AB - Apparently depression ran in this man's family, and when he took an overdose of his tricyclic antidepressant, he also took the tricyclics of his mother and his sister. Most patients who die of an overdose of a tricyclic antidepressant are pronounced dead without reaching a hospital, and those who die after arriving in the emergency room do so within a few hours.2 Central nervous system toxicity of tricyclic antidepressants may manifest as confusion, agitation, hallucinations, coma, myoclonus, or seizures. Generalized seizures often presage cardiopulmonary arrest,2 and within 20 seconds of the ECG with evidence of generalized seizure activity shown here, the QRS duration increased from 188 ms to 212 ms, and the patient died soon thereafter. PMID- 27383861 TI - Radiology Case Of The Month: Brain Magnetic Resonance Imaging with Bilateral Hyperintensities in the Globus Pallidi. AB - An MRI of the brain and spine of an 11-year-old male revealed the following abnormality which is consistent with his chronic condition. PMID- 27383862 TI - Pathology Image Of The Month: Recurrent Urinary Tract Infections In a 48-year-Old Female Hyperintensities in the Globus Pallidi. AB - A 48-year-old female presented to her physician complaining of intermittent lower abdominal pain radiating to the right lower back. At the time of presentation, she was afebrile and denied any urinary symptoms such as dysuria, frequency or urgency. Physical exam was unremarkable, other than obesity, and her abdominal exam was noncontributory. Medical history, however, was notable for recurrent, Proteus mirabilis culture-proven urinary tract infections requiring antibiotic treatment for the prior three years along with hypertension, uterine fibroids post hysterectomy, diabetes and asthma. Complete blood count was within normal limits, and urine dipstick showed 1+ blood, 1+ protein and 2+ leukocytes. Full renal function labs, urine cytology, radioisotope renography and abdominopelvic CT scanning with contrast were all ordered and a laparoscopic right nephrectomy was recommended based on the results. The bisected right kidney is shown below in Figure 1. She was discharged home on post-operative day one and her follow up urology appointments indicate resolution of both her urinary tract infections and her abdominal pain. PMID- 27383863 TI - Characterization of Mentorship Programs in Departments of Surgery in the United States. AB - Importance: Mentorship is considered a key element for career satisfaction and retention in academic surgery. Stakeholders of an effective mentorship program should include the mentor, the mentee, the department, and the institution. Objective: The objective of this study was to characterize the status of mentorship programs in departments of surgery in the United States, including the roles of all 4 key stakeholders, because to our knowledge, this has never been done. Design, Setting, and Participants: A survey was sent to 155 chairs of departments of surgery in the United States in July 2014 regarding the presence and structure of the mentorship program in their department. The analysis of the data was performed in November 2014 and December 2014. Main Outcomes and Measures: Presence and structure of a mentorship program and involvement of the 4 key stakeholders. Results: Seventy-six of 155 chairs responded to the survey, resulting in a 49% response rate. Forty-one of 76 of department chairs (54%) self reported having an established mentorship program. Twenty-five of 76 departments (33%) described no formal or informal pairing of mentors with mentees. In 62 (82%) and 59 (78%) departments, no formal training existed for mentors or mentees, respectively. In 42 departments (55%), there was no formal requirement for the frequency of scheduled meetings between the mentor and mentee. In most departments, mentors and mentees were not required to fill out evaluation forms, but when they did, 28 of 31 were reviewed by the chair (90%). In 70 departments (92%), no exit strategy existed for failed mentor-mentee relationships. In more than two-thirds of departments, faculty mentoring efforts were not recognized formally by either the department or the institution, and only 2 departments (3%) received economic support for the mentoring program from the institution. Conclusions and Relevance: These data show that only half of departments of surgery in the United States have established mentorship programs, and most are informal, unstructured, and do not involve all of the key stakeholders. Given the importance of mentorship to career satisfaction and retention, development of formal mentorship programs should be considered for all academic departments of surgery. PMID- 27383864 TI - An expeditious synthesis of early transition metal carbide nanoparticles on graphitic carbons. AB - An expeditious synthesis of metal carbide nanoparticles onto various carbon supports is demonstrated. The procedure is versatile and readily yields TiC, VC, Mo2C and W2C nanoparticles on different types of carbons. The reaction is initiated at room temperature and proceeds within seconds. This novel synthetic route paves the way for a large variety of metal carbide-carbon nanocomposites that may be implemented in emerging nanotechnology fields. PMID- 27383865 TI - Adolescent education: an opportunity to create a Developmental Origins of Health and Disease (DOHaD) circuit breaker. AB - Health before conception, and periconceptional nutritional environments, contribute to conditioning of later-life health and disease. Health behaviors developed during adolescence continue into adulthood. Thus, even when the gap between pregnancy and adolescence is substantial, behaviors developed during adolescence influence later-life non-communicable disease (NCD) vulnerability in offspring. Consequently, adolescence is an important life phase where development of positive health behaviors can contribute to disruption of transgenerational cycles of NCD risk. Schooling is a core activity during adolescence. Modern curricula focus on development of capabilities associated with critical, engaged citizenship, empowering learning that supports action-based engagement in complex issues. Contexts relevant to adolescents and their communities, such as the NCD epidemic, are used to facilitate learning. Thus, engaging the education sector as participants in the work of the Developmental Origins of Health and Disease community offers an important strategy to capture the potential of adolescence as a life stage for transgenerational primary prevention of obesity and NCD risk. PMID- 27383866 TI - (Don't) Mind the effort: Effects of contextual interference on ERP indicators of motor preparation. AB - Motor learning is associated with a decrease in frontal control-related brain activity and increase of central and parietal motor-related activity. Contextual interference (CI), manipulated typically by blocked versus randomized training schedules, affects motor learning, resulting in inferior performance during training but in superior performance during retention and transfer. The CI effect is often explained by increased processing demands under high CI training. Consistently, in the motor preparation phase, the activity of control- and attention-related brain areas is increased under high CI. Here, we investigated the effect of CI on learning-related changes in ERPs during motor preparation. Participants learned throwing at virtual targets and were tested for retention in the target condition 1 week later. The frontal P3 component decreased with learning during the first session and across sessions. In addition, there was a trend for a stronger reduction of P3 during retention after high CI training. Both initial and late contingent negative variation (iCNV and lCNV) amplitudes decreased with learning and showed a significantly stronger reduction under high CI. We conclude that CI modulates the interplay of cognitive and motor processes in the preparatory phase of motor learning and that a stronger involvement of cognitive processes during high CI training accounts for differential effects of CI on ERP indicators of motor preparation during retention. PMID- 27383867 TI - History of chemical sensitivity and diagnosis. AB - Histories of mold, pollen, dust, food, chemicals, and electromagnetic field (EMF) sensitivities are the major categories of triggers for chemical sensitivity. They are tied together by the coherence phenomenon, where each has its own frequencies and identifiable EMF; therefore, they can be correlated. The diagnosis of chemical sensitivity can be done accurately in a less-polluted, controlled environment, as was done in these studies. The principles of diagnosis and treatment depend on total environmental and total body pollutant loads, masking or adaptation, bipolarity of response, and biochemical individuality, among others. These principles make less-polluted, controlled conditions necessary. The clinician has to use less-polluted water and organic food with individual challenges for testing, including dust, mold, pesticide, natural gas, formaldehyde, particulates, and EMF testing, which needs to be performed in less polluted copper-screened rooms. The challenge tests for proof of chemical sensitivity include inhaled toxics within a clean booth that is chemical- and particulate-free at ambient doses in parts per million (ppm) or parts per billion (ppb). Individual foods, both organic and commercial (that are contaminated with herbicides and pesticides), are used orally. Water testing and intradermal testing are performed in a less-polluted, controlled environment. These include specific dose injections of molds, dust, and pollen that are preservative-free, individual organic foods, and individual chemicals, i.e. methane, ethane, propane, butane, hexane, formaldehyde, ethanol, car exhaust, jet fuel exhaust, and prosthetic implants (metal plates, pacemakers, mesh, etc.). Normal saline is used as a placebo. EMF testing is performed in a copper-screened room using a frequency generator. In our experience, 80% of the EMF-sensitive patients had chemical sensitivity when studied under less-polluted conditions for particulates, controlled natural gas, pesticides, and chemicals like formaldehyde. PMID- 27383868 TI - Decreased undercarboxylated osteocalcin in children with type 2 diabetes mellitus. AB - BACKGROUND: Osteocalcin (OC) is a bone-specific protein secreted by osteoblasts and often used as a bone formation biomarker. OC undergoes post-translational carboxylation to yield carboxylated osteocalcin (Gla-OC) and undercarboxylated osteocalcin (uc-OC) molecules. The aim of this study was to explore the association between bone and glucose metabolism by evaluating OC, ionized cations, and markers of glucose metabolism in children with obesity and type 2 diabetes mellitus (DM2). METHODS: The subjects were nine children with DM2 [six males, three females; age 15.7+/-4.1 years; duration of disease 3.2+/-1.2 years], 18 children with simple obesity [12 males, six females; age 12.6+/-4.1 years], and 12 controls [eight males, four females; age 12.3+/-3.2 years]. Serum Gla-OC and uc-OC levels were determined using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with DM2 (0.65+/-0.46 ng/mL), but not with obesity (1.11+/-0.55 ng/mL), had lower uc-OC levels than controls (1.25+/-0.49 ng/mL). Serum uc-OC was negatively correlated with mean serum glucose levels (r=-0.447, p=0.013) and hemoglobin A1c (HbA1c) (r=-0.455, p=0.012) in all subjects. Serum Gla-OC was correlated with serum alkaline phosphatase (r=0.601, p<0.001) and inorganic phosphorus (r=0.686, p<0.001), yet negatively correlated with age (r= 0.383, p=0.030). Mean serum ionized magnesium was lower in DM2 subjects than in controls. Mean serum ionized calcium was higher in obese subjects than in controls. In all subjects, mean serum ionized magnesium was negatively correlated with mean serum glucose levels. CONCLUSIONS: Osteoblast-derived protein OC, especially uc-OC, may have a role in the pathophysiology of diabetes by being associated with blood glucose homeostasis. PMID- 27383869 TI - Hyperinsulinism-hyperammonemia syndrome: a de novo mutation of the GLUD1 gene in twins and a review of the literature. AB - Hyperinsulinism-hyperammonemia (HI/HA) syndrome is a rare autosomal dominant disease characterized by recurrent hypoglycemia and persistent mild elevation of plasma ammonia. HI/HA syndrome is one of the more common forms of congenital hyperinsulinism (CHI), caused by activating mutations within the GLUD1 gene that encodes the mitochondrial enzyme glutamate dehydrogenase (GDH). We report here on monozygotic twin girls presented with fasting- and protein-induced hypoglycemia and mild persistent hyperammonemia. Genetic analysis revealed that both girls were heterozygous for a novel missense mutation within exon 11 [c.1499A>T, p.(R443W)] of the GLUD1 gene. Despite early treatment with diazoxide and a low protein diet, they both developed non-hypoglycemic seizures in early childhood followed by cognitive impairment. In addition to their clinical course, a review of the literature on HI/HA syndrome is provided. PMID- 27383870 TI - Treatment of trigeminal neuralgia by radiofrequency of the Gasserian ganglion. AB - Trigeminal neuralgia (TN) is a neuropathic pain disorder that affects the trigeminal nerve distribution area. Pharmacological therapy has remained the first-line treatment for TN. If pharmacological intervention is not effective, surgical treatments including radiosurgery (mainly gamma knife therapy), radiofrequency (RF) of the Gasserian ganglion, and microvascular decompression have been utilized. RF is one of the most common procedures used to treat TN. Two RF approaches are commonly utilized: conventional radiofrequency (CRF) and pulsed radiofrequency (PRF). Both methods have been used to successfully treat TN; however, each procedure has distinct advantages and disadvantages. This article summarizes the current relevant literature to compare the treatment of TN with CRF vs. PRF. We discuss the treatment indications, operative methods, and complications of each treatment strategy. Most of the patients treated with CRF had a satisfactory outcome, whereas most PRF patients still had significant pain after the procedure. The application of a higher voltage can improve the curative effect of PRF, and its complications are less than CRF. Both CRF and PRF can be used to treat TN, and the former was more effective. Although the complications of CRF are more than those of PRF, most of them were short-lived and lacked sequelae. The pain relief rate in PRF-treated patients was significantly lower compared to CRF-treated patients. Furthermore, recurring pain was more commonly observed in PRF-treated patients. Therefore, CRF may be the preferred treatment option for TN, whereas treatment with PRF requires further study. PMID- 27383871 TI - Anti-nociceptive and anti-inflammatory effects of Withania somnifera root in fructose fed male rats. AB - BACKGROUND: Insulin resistance is a metabolic disorder which affects the diabetes mellitus pathophysiology and alters the cell excitability. This study has been designed to evaluate the anti-nociceptive and anti-inflammatory effects of chronic administration of Withania somnifera root (WSR) in fructose drinking water rats. METHODS: An experiment was carried out on 48 Wistar-Albino male rats, weighting 200+/-30 g, which were divided into six groups (n=8): control group (C), control morphine (CM), W. somnifera group (WS) which received WSR (62.5 mg/g diet), W. somnifera naloxone group (WSN) which received WSR and naloxone, fructose (F) group which received fructose drinking water and FWS group which received fructose-enriched drinking water and WSR during the trial period. A biphasic pain response was induced after intraplantar injection of formalin (50 MUL, 1%). Pain behavior was measured using Dubuisson methods. The obtained data were analyzed by SPSS software V. 18, using ANOVA and Tukey test. Results were expressed as mean+/-SD. Statistical differences were considered significant at p<0.05. RESULTS: The results showed that the insulin resistance index, blood sugar, insulin, IL-6, TNF-alpha, and acute and chronic pain score in the F group were significantly increased in comparison with the control group, but these parameters in the FWS group were significantly decreased compared with the F group (p<0.001). CONCLUSIONS: Our findings indicated that chronic oral administration of WSR has analgesic and anti-inflammatory effects in fructose drinking water rats and causes improved insulin resistance index. PMID- 27383872 TI - Medical and Social Aspects of Syphilis in the Balkans from the mid-19th Century to the Interwar. AB - The current study presents some aspects of syphilis in the Balkan Peninsula from the 19th century until the Interwar. Ever since the birth of modern Balkan States (Greece, Bulgaria, Turkey and Serbia), urbanization, poverty and the frequent wars have been considered the major factors conducive to the spread of syphilis. The measures against sex work and sexually transmitted diseases (STDs) were taken in two aspects, one medical and the other legislative. In this period, numerous hospitals for venereal diseases were established in the Balkan countries. In line with the international diagnostic approach and therapeutic standards, laboratory examinations in these Balkan hospitals included spirochete examination, Wassermann reaction, precipitation reaction and cerebrospinal fluid examination. Despite the strict legislation and the adoption of relevant laws against illegal sex work, public health services were unable to curb the spread of syphilis. Medical and social factors such as poverty, citizen's ignorance of STDs, misguided medical perceptions, lack of sanitary control of prostitution and epidemiological studies, are highlighted in this study. These factors were the major causes that helped syphilis spread in the Balkan countries during the 19th and early 20th century. The value of these aspects as a historic paradigm is diachronic. Failure to comply with the laws and the dysfunction of public services during periods of war or socioeconomic crises are both factors facilitating the spread of STDs. PMID- 27383873 TI - Cognitive Impairment in Schizophrenia, Neurotransmitters and the New Atypical Antipsychotic Aripiprazole. AB - Cognition is a group of mental processes that includes the capacity to perceive, think, learn and to study, and the capacity of the brain to analyze information and program adaptive behaviour. Although there has been an appreciable evolution in the therapy of psychoses in the last twenty-five years, cognitive disturbances still persist in spite of antipsychotic treatment. The cognitive decay disrupts the ability of clinically diagnosed patients with psychoses, mainly schizophrenia, to learn and to memorize skills that are useful for their family and social relationships. Moreover, cognitive deficiency is often considered to be crucial for further rehabilitation. In atypical antipsychotics there are big differences in the effects on cognitive functions. Some clinical studies demonstrate the benefits of a third generation of antipsychotics on cognitive functions in patients treated for mental illnesses. In the present study we have reviewed many articles investigating the influence of aripiprazole on cognition in human and animal subjects. Aripiprazole is a third generation antipsychotic drug that possesses a unique pharmacodynamic profile, which in conjunction with recently published scientific data on the drugs' influence on antidepressant, anxiolytic and cognitive functions, suggests a highly positive future potential for restorative cognitive treatment and ongoing healthy function. The data included in the review will contribute to determining the potential benefits of aripiprazole on memory and training processes. PMID- 27383874 TI - A Prospectus of Tenomodulin. AB - Tenomodulin is a type II transmembrane glycoprotein that can regulate growth of tendon. The human tenomodulin encoding gene is mapped to X chromosome and encodes a polypeptide consisting of 317 alpha amino acids. The protein is located on the cell surface as N-glycosylated or non-N-glycosylated polypeptide with molecular mass of 45 and 40 kDa, respectively. The molecule consists of three domains and a short cytoplasmic tail at N-terminus. Tenomodulin is predominantly expressed in dense connective hypovascularized tissues such as tendons, skeletal muscle epimysium, and ligaments. Furthermore, tenomodulin is an efficient marker of tenocyte differentiation and plays an important role in the regulation of tenocyte proliferation, tendon development, and angiogenesis inhibition. A number of tenomodulin gene polymorphisms have been recently associated with a risk of obesity, diabetes, systemic immune mediators, cholesterol levels, Alzheimer disease, and age-related macular degeneration. Tenomodulin is involved in cell adhesion, determination of cell morphology, cell aging and bone mineral density. It is expected to play an important role in tendon recovery, tendon tissue engineering, anti-tumor therapy, treatment of chordal disruption, and remodeling of extracellular matrix. PMID- 27383875 TI - Immunophenotypic Modulation of the Blast Cells in Childhood Acute Lymphoblastic Leukemia Minimal Residual Disease Detection. AB - Early clearance of leukemic cells during induction therapy of childhood acute lymphoblastic leukemia (ALL) is a basis for treatment optimization. Currently, the most widely used methods for the detection of minute residual malignant cells in the bone marrow and/or peripheral blood, minimal residual disease (MRD), are PCR and flow cytometry (FCM). Immunophenotypic modulation (IM) is a well known factor that can hamper the accurate FCM analysis. AIM: To report the IM detected by 8-color FCM during the BFM-type remission induction in 24 consecutive MRD positive samples of children with B-cell precursor ALL and the possible implications for MRD detection. PATIENTS AND METHODS: Between 2010 and 2012 we prospectively followed up the MRD on days 15 and 33 of induction treatment in bone marrow (BM) samples and on day 8 in peripheral blood (PB). The IM was assessed by comparative analyses of the changes in the mean fluorescence intensity of 7 highly relevant antigens expressed by the leukemic cells and normal B-lymphocytes. RESULTS: IM occurred, to different extents, in all analyzed day 15 BM and in most day 33 BM samples. Statistically significant changes in the MFI-levels of four CDs expressed by the leukemic blasts were observed: downmodulation of CD10, CD19 and CD34 and upmodulation of CD20. No changes in the expression of CD38, CD58 and CD45 were noticed. CONCLUSIONS: Measuring the MRD by standardized 8-color flow cytometry helps improve the monitoring of the disease, leading to better therapeutic results. However, the IM of the different antigens expressed by the leukemic blasts should be taken into consideration and cautiously analyzed. PMID- 27383877 TI - Eyelid Reconstruction with Full Thickness Skin Grafts After Carcinoma Excision. AB - BACKGROUND: Various techniques have been proposed for reconstruction of the eyelid anterior lamella after carcinoma excision: among these are the transposition of skin flaps, and full-thickness skin grafts or combination of these two. AIM: To present our experience in eyelid reconstruction with full thickness skin grafts and to assess the aesthetic and functional outcomes. PATIENTS AND METHODS: The present retrospective study included 39 patients (20 males, 19 females, mean age 71 yrs) with surgically excised eyelid carcinoma, followed by reconstruction using full-thickness skin grafts. The patients were treated between 2005 and 2014. Parameters recorded were patient demographics, histological classification of malignancy, tumor localization and size, postoperative defect size. In cases of large full-thickness lower lid defect Hughes tarsoconjunctival flap was used for reconstruction of posterior lamella. Full-thickness skin grafts donor sites included upper eyelid, preauricular area and inner brachial area. We appraised the grafts viability one week after surgery and the aesthetic results - 6 months after surgery by the graft colour and lid position. RESULTS: In 95% of the cases the skin grafts were viable. The full thickness skin graft (FTSG) failed in two patients because of subcutaneous haematoma. There were a few early postoperative complications including graft hypertrophy, graft contraction, and partial graft failure, which were managed without additional surgery. All 39 patients had normal postoperative lid function. All 39 had either good (14) or excellent (25) cosmetic results. CONCLUSIONS: Our findings suggest that full-thickness skin graft is a good choice in periocular reconstructive surgery after carcinoma excision. The surgical technique is easy to perform producing proper functional and aesthetic results. PMID- 27383876 TI - Diabetes Mellitus Type 2 in Hospitalized COPD Patients: Impact on Quality of Life and Lung Function. AB - INTRODUCTION: Diabetes mellitus (DM) is estimated to affect 2-37% of COPD patients, results varying widely between studies. DM may also correlate with quality of life and lung function. AIM: To examine correlations between DM and quality of life and lung function in COPD patients admitted to hospital with exacerbation of COPD. PATIENTS AND METHODS: A hundred and fifty-two patients were included in the study. They were all examined for diabetes mellitus. All patients completed CAT and mMRC questionnaires and underwent spirometry. RESULTS: 13.2% (20/152) of patients received medications for DM. 21.7% (33/152) had newly diagnosed DM and 30.9% (47/152) had prediabetes. DM is not associated with reduced quality of life and worse pulmonary function. However, untreated DM is associated with both reduced quality of life and worse pulmonary function. HbA1c is negatively correlated with FVC and positively correlated with CAT score. CONCLUSIONS: COPD patients hospitalized for exacerbation are at high risk for impaired glucose metabolism. Untreated DM is associated with worse lung function and lower quality of life, which stresses the importance of screening for the disease. The patients may benefit from optimizing blood glucose level. PMID- 27383878 TI - Lack of ERG-antibody in Benign Mimickers of Prostate Cancer. AB - INTRODUCTION: Prostate carcinoma (PC) is the second most diagnosed cancer in men worldwide. Prostate tissue in needle biopsy expresses a wide variety of architectural patterns some of which are difficult to interpret. Immunohistochemical markers, such as AMACR, p63 and 34betaE12 that are currently used in diagnosing prostate cancer, are of great value, but often their interpretation is ambiguous. In 2005 Tomlins et al. identified an emerging marker, erythroblastosis E26 rearrangement gene (ERG), which is a member of the family of genes encoding erythroblast-transformation specific transcription factors (ETS) with frequent expression in PC. AIM: The aim of this study was to investigate the expression of ERG in benign mimickers of PC in needle biopsies and its diagnostic value alone and in combination with AMACK and 34betaE12. RESULTS: Of the selected 46 biopsies, two were eventually diagnosed as PC Gleason score 6 as they were simultaneously ERG and AMACR-positive and 34betaE12 negative. One case was considered atypical. The remaining 43 biopsies were diagnosed as benign cases: simple atrophy in 13 cases, partial atrophy in 11, adenosis in 9, basal cell hyperplasia in 3, post-atrophic hyperplasia in 3, clear cell hyperplasia in 2 and sclerotic adenosis in 2 cases. None of the 43 benign cores showed evidence of ERG expression. CONCLUSION: ERG could be preferably used in diagnosing prostate needle biopsies, lesions that are hard to interpret and controversial expression of AMACR/34betaE12. PMID- 27383879 TI - Scanning Electron Microscopy of Enamel and Dentin of Teeth with Hypocalcified Amelogenesis Imperfecta. AB - The histological features of teeth with hypocalcified amelogenesis imperfecta (AI) have been poorly studied, which calls into question the effectiveness of modern adhesive techniques used in the treatment of these noncarious defects. AIM: The aim of this study was to investigate the morphological features of the enamel and dentin of teeth with AI using scanning electron microscopy (SEM), and compare these features with those of healthy teeth. MATERIALS AND METHODS: We examined four primary teeth extracted on indication from a 10-year-old girl with hypocalcified amelogenesis imperfecta. The same number of primary teeth extracted from healthy subjects was used as controls. The morphological characteristics of the enamel and dentin are described after investigating the teeth and photographing the specimens with scanning electron microscope. RESULTS: The SEM photos of the enamel of AI teeth show presence of external defects, incorrectly oriented enamel prisms and enlarged interprism spaces. Thickening of the peritubular dentin and partially obliterated dentinal tubules characterize the dentin of these teeth. CONCLUSION: The enamel and dentin of teeth affected by hypocalcified AI diff er considerably from normal hard dental structures in their morphological characteristics. PMID- 27383880 TI - Symptomatic Os Subtibiale Associated with Chronic Pain Around the Medial Malleolus in a Young Athlete. AB - An os subtibiale is a rare accessory bone located below or behind the medial malleolus. Herein we present a rare case of a painful os subtibiale in a young triathlete who presented with pain, redness and swelling below his left medial malleolus. Plain radiographs and three-dimensional computed tomography revealed a well-defined oval bone distal to the left medial malleolus. After conservative treatment failed, the ossicle was excised in an open surgery with complete resolution of symptoms. This case report emphasizes the need for clinical awareness of different anatomical variations of the bones of the foot. PMID- 27383881 TI - Homozygous Carrier of Prothrombin G20210A Mutation with Massive Pulmonary Embolism and His Family: Gender Differences of Susceptibility to Mutation. AB - Prothrombin 20210 G>A mutation is the second most frequent inherited factor increasing the risk for developing venous thromboembolism (VTE). The risk for VTE in homozygous carriers of this mutation is not well studied because of their rarity are rare. We report a case of a homozygous carrier of prothrombin mutation: a young man with massive pulmonary embolism, and his family - an asymptomatic homozygous sister, heterozygous parents with asymptomatic mother, and father with history of deep venous thrombosis (DVT). To our knowledge, this is the first reported case of homozygous prothrombin mutation carriers in Bulgaria and the other Balkan countries. We conclude that the homozygous prothrombin mutation creates predisposition for VTE that can manifest or not depending on additional factors, one of which could be male gender. PMID- 27383882 TI - Development of molecules stimulating the activity of KLK3 - an update. AB - Kallikrein-related peptidase-3 (KLK3, known also as prostate-specific antigen, PSA) is highly expressed in the prostate. KLK3 possess antiangiogenic activity, which we have found to be related to its proteolytic activity. Thus, it may be possible to slow down the growth of prostatic tumors by enhancing this activity. We have developed peptides that enhance the proteolytic activity of KLK3. As these peptides are degraded in circulation and rapidly excreted, we have started to modify them and have succeeded in creating bioactive and more stable pseudopeptides. We have also identified small molecules stimulating the activity of KLK3, especially in synergy with peptides. PMID- 27383883 TI - Application of instrumented nanoindentation in preformulation studies of pharmaceutical active ingredients and excipients. AB - Nanoindentation allows quantitative determination of a material's response to stress such as elastic and plastic deformation or fracture tendency. Key instruments that have enabled great advances in nanomechanical studies are the instrumented nanoindenter and atomic force microscopy. The versatility of these instruments lies in their capability to measure local mechanical response, in very small volumes and depths, while monitoring time, displacement and force with high accuracy and precision. This review highlights the application of nanoindentation for mechanical characterization of pharmaceutical materials in the preformulation phase (primary investigation of crystalline active ingredients and excipients). With nanoindentation, mechanical response can be assessed with respect to crystal structure. The technique is valuable for mechanical screening of a material at an early development phase in order to predict and better control the processes in which a material is exposed to stress such as milling and compression. PMID- 27383884 TI - Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activities. AB - 6'-(4-Chlorophenyl)-spiro[cyclohexane-1,2'-thieno[3,2-d][1,3] oxazin]-4'(1'H)-one (1) was synthesized and used as a starting material for the synthesis of a novel series of spiro compounds having biologically active sulfonamide 2a-e and 3'-(4 acetylphenyl)-6'- (4-chlorophenyl)-1'H-spiro[cyclohexane-1,2'-thieno[3,2-d] pyrimidine-4'(3'H)-one (3). Compound 2a was used as a key intermediate for the synthesis of sulfonyl carbothioamide derivatives 4a-c. Also, compound 3 was used as an intermediate for the synthesis of 3'H-spiro[cyclohexane-1,2'-thieno[3,2 d]pyrimidin]-3'-yl] phenyl}-2-imino-4-(substituted phenyl and/or thienyl)-1,2 dihydropyridine- 3-carbonitrile derivatives 5a-e, 3'H-spiro[cyclohexane- 1,2'- thieno[3,2-d]pyrimidin]-3'-yl]phenyl}-2-oxo-4-(substituted phenyl and/or thienyl) 1,2-dihydropyridine-3-carbonitrile derivatives 6a-e, and 4-[(2Z)-3-substituted arylprop-2-enoyl] phenyl-1'H-spiro[cyclohexane-1,2'-thieno[3,2-d]pyrimidine derivatives 7a-e. Cyclocondensation of 7a-e with hydrazine hydrate produced 6'-(4 chlorophenyl)-3'-[4-(5-substituted aryl-4,5-dihydro- 1H-pyrazol-3-yl)phenyl]-1'H spiro[cyclohexane-1,2'-thieno- [3,2-d]pyrimidin]-4'(3'H)-ones 8a-e but with hydroxylamine hydrochloride afforded the corresponding isoxazoline derivatives 9a e. Also, cyclocondensation by thiourea afforded 2-thioxo-1,2- dihydropyrimidin-4 yl)-phenyl-spiro-{cyclohexanethieno[3,2-d] pyrimidin}-4-one derivatives 10a-e. The new compounds were investigated for antimicrobial activity. Compounds 2c, 8b,c, 9b and 10b were the most potent ones against both Gram-negative and Gram positive bacteria. Compound 8c exhibited higher antifungal activity towards the examined fungi with MIC of 1-2 MUmol mL-1 compared to ketoconazole (MIC 2-3 MUmol mL-1 ). PMID- 27383885 TI - Design, synthesis and evaluation of benzofuran-acetamide scaffold as potential anticonvulsant agent. AB - A series of N-(2-(benzoyl/4-chlorobenzoyl)-benzofuran- 3-yl)-2-(substituted) acetamide derivatives (4a-l, 5a-l) was synthesized in good yield. All synthesized compounds were in agreement with elemental and spectral data. The anticonvulsant activity of all synthesized compounds was assessed against the maximal electroshock induced seizures (MES) model in mice. Neurotoxicity was evaluated using the rotarod method. The majority of compounds exhibited anticonvulsant activity at a dose of 30 mg kg-1 body mass during 0.5-4 h, indicating their ability to prevent seizure spread at low doses. Relative to phenytoin, [N-(2-(4 chlorobenzoyl)benzofuran-3-yl)-2-(cyclohexyl( methyl) amino)-acetamide] (5i) and [N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(4-methylpiperidin-1- yl)-acetamide] (5c) demonstrated comparable relative anticonvulsant potency of 0.74 and 0.72, respectively, whereas [(N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(4-(furan-2 carbonyl)-piperazin-1-yl)-acetamide] (5f) exhibited the lowest relative potency of 0.16. The ALD50 of tested compounds ranged from 1.604 to 1.675 mmol kg-1 body mass. The ED50 of synthesized compounds ranged from 0.055 to 0.259 mmol kg-1 (~23.4 to 127.6 mg kg-1) body mass. The pharmacophore mapping of the examined compounds on standard drugs (phenobarbital, phenytoin, ralitolin and carbamazepine) strongly suggests that these compounds may exert their anticonvulsant activity via the same established mechanism as that of known drugs. PMID- 27383886 TI - A new biocompatible delivery scaffold containing heparin and bone morphogenetic protein 2. AB - Silicon-substituted calcium phosphate (Si-CaP) was developed in our laboratory as a biomaterial for delivery in bone tissue engineering. It was fabricated as a 3D construct of scaffolds using chitosan-trisodium polyphosphate (TPP) cross-linked networks. In this study, heparin was covalently bonded to the residual -NH2 groups of chitosan on the scaffold applying carbodiimide chemistry. Bonded heparin was not leached away from scaffold surfaces upon vigorous washing or extended storage. Recombinant human bone morphogenetic protein 2 (rhBMP-2) was bound to conjugated scaffolds by ionic interactions between the negatively charged SO42- clusters of heparin and positively charged amino acids of rhBMP-2. The resulting scaffolds were inspected for bone regenerative capacity by subcutaneous implanting in rats. Histological observation and mineralization assay were performed after 4 weeks of implantation. Results from both in vitro and in vivo experiments suggest the potential of the developed scaffolds for bone tissue engineering applications in the future. PMID- 27383887 TI - Bioactive chemical constituents of Curcuma longa L. rhizomes extract inhibit the growth of human hepatoma cell line (HepG2). AB - The present study was designed to identify the chemical constituents of the methanolic extract of Curcuma longa L. rhizomes and their inhibitory effect on a hepatoma cell line. The methanolic extract was subjected to GC-MS analysis to identify the volatile constituents and the other part of the same extract was subjected to liquid column chromatographic separation to isolate curcumin. The inhibition of cell growth in the hepatoma cell line and the cytopathological changes were studied. GC-MS analysis showed the presence of fifty compounds in the methanolic extract of C. longa. The major compounds were ar-turmerone (20.50 %), beta-sesquiphellandrene (5.20 %) and curcumenol (5.11 %). Curcumin was identified using IR, 1H and 13C NMR. The inhibition of cell growth by curcumin (IC50 = 41.69 +/- 2.87 MUg mL-1) was much more effective than that of methanolic extract (IC50 = 196.12 +/- 5.25 MUg mL-1). Degenerative and apoptotic changes were more evident in curcumin- treated hepatoma cells than in those treated with the methanol extract. Antitumor potential of the methanolic extract may be attributed to the presence of sesquiterpenes and phenolic constituents including curcumin (0.051 %, 511.39 MUg g-1 dried methanol extract) in C. longa rhizomes. PMID- 27383888 TI - PF573,228 inhibits vascular tumor cell growth, migration as well as angiogenesis, induces apoptosis and abrogates PRAS40 and S6RP phosphorylation. AB - PF573,228 is a compound that targets focal adhesion kinase (FAK), a non-receptor protein kinase, which is over-expressed in various tumors. The aim of this study was to evaluate the effects of PF573,228 on the cells derived from mouse vascular tumors, namely, endothelioma cells. The treatment of endothelioma cells with PF573,228 reduced their growth with an IC50 of approximately 4.6 MUmol L-1 and inhibited cell migration with an IC50 of about 0.01 MUmol L-1. Microscopic studies revealed morphological attributes of apoptosis. These observations were confirmed by ELISA, which showed increased caspase-3 activity. PF573,228 also inhibited angiogenesis in a dose-dependent manner, with an IC50 of approximately 3.7 MUmol L-1, and abrogated the phosphorylation of cell survival proteins, proline-rich Akt substrate (PRAS40) and S6 ribosomal protein (S6RP). Array data further revealed that PF573,228 induced caspase-3 activation, thus promoting apoptosis. Since all the processes inhibited by PF573,228 provide important support to tumor survival and progression, the drug may have a potential role in the treatment of vascular tumors. PMID- 27383889 TI - Olive leaf extract activity against Candida albicans and C. dubliniensis - the in vitro viability study. AB - Olive leaf extract is characterized by a high content of polyphenols (oleuropein, hydroxytyrosol and their derivatives), which is associated with its therapeutic properties. The objective of the present research was to evaluate the antifungal activity of olive leaf extract against Candida albicans ATCC 10231 and C. dubliniensis CBS 7987 strains. Minimum inhibitory concentrations (MIC) of the extract were determined by several in vitro assays. The extract showed a concentration depended effect on the viability of C. albicans with MIC value of 46.875 mg mL-1 and C. dubliniensis with MIC value 62.5 mg mL-1. Most sensitive methods for testing the antifungal effect of the extracts were the trypan blue exclusion method and fluorescent dye exclusion method while MIC could not be determined by the method according to the EUCAST recommendation suggesting that herbal preparations contain compounds that may interfere with this susceptibility testing. The fluorescent dye exclusion method was also used for the assessment of morphological changes in the nuclei of treated cells. According to the obtained results, olive leaf extract is less effective against the tested strains than hydroxytyrosol, an olive plant constituent tested in our previous study. PMID- 27383890 TI - Evaluation of pancreatin stability through enzyme activity determination. AB - Pancreatin is a biotechnological product containing an enzyme complex, obtained from porcine pancreas, that is employed in treating pancreatic diseases. Experiments regarding the stability of the pharmaceutical formulation containing pancreatin were performed using standard binary mixtures with 6 excipients in a 1:1 ratio (m/m) and a commercial formulation. To accomplish these goals, samples were stored for 1, 3 and 6 months at 40 +/- 1 degrees C and 75 +/- 5 % relative humidity (RH) and 40 +/- 1 degrees C and 0 % RH. Stress testing was also performed. All samples were analyzed to evaluate the alpha-amylase, lipase and protease activities through UV/Vis spectrophotometry. The results revealed that the excipient proprieties and the storage conditions affected enzyme stability. Humidity was a strong influencing factor in the reduction of alpha-amylase and protease activities. Stress testing indicated that pH 9.0 and UV light did not induce substantial alterations in enzyme activity. PMID- 27383891 TI - A study of compressibility and compactibility of directly compressible tableting materials containing tramadol hydrochloride. AB - The paper evaluates and compares the compressibility and compactibility of directly compressible tableting materials for the preparation of hydrophilic gel matrix tablets containing tramadol hydrochloride and the coprocessed dry binders Prosolv(r) SMCC 90 and DisintequikTM MCC 25. The selected types of hypromellose are MethocelTM Premium K4M and MethocelTM Premium K100M in 30 and 50 % concentrations, the lubricant being magnesium stearate in a 1 % concentration. Compressibility is evaluated by means of the energy profile of compression process and compactibility by the tensile strength of tablets. The values of total energy of compression and plasticity were higher in the tableting materials containing Prosolv(r) SMCC 90 than in those containing DisintequikTM MCC 25. Tramadol slightly decreased the values of total energy of compression and plasticity. Tableting materials containing Prosolv(r) SMCC 90 yielded stronger tablets. Tramadol decreased the strength of tablets from both coprocessed dry binders. PMID- 27383892 TI - Effect of cerebrolysin on dopaminergic neurodegeneration of rat with oxidative stress induced by 3-nitropropionic acid. AB - The study tested the hypothesis that cerebrolysin protects the brain from free radicals in rats treated with 3-nitropropionic acid (3-NPA). To address this hypothesis, the levels of dopamine (DA) and some oxidative stress biomarkers were measured after administration of 3-NPA. Young male Fischer rats were treated for three days with cerebrolysin, 3-NPA or both substances. Their brains were extracted, and DA, lipid peroxidation (LP), glutathione (GSH), calcium, and H2O2 were measured using validated methods. In the cortex, hemispheres and cerebellum/medulla oblongata of the group treated with cerebrolysin and 3-NPA, the levels of DA and LP decreased. In addition, calcium and H2O2 levels decreased in the hemispheres of the same group, while GSH increased in cortex. The increased dopamine metabolism due to the administration of cerebrolysin led to increased formation of radical species and oxidative stress, especially when free radicals were generated by 3-NPA. PMID- 27383893 TI - Successful prevention of preeclampsia in a high-risk pregnancy using progestogen dydrogesterone: a clinical case. AB - The presented clinical example convincingly demonstrates the efficacy of dydrogesterone (30 mg) in the prevention of severe preeclampsia in a high-risk patient (early development of preeclampsia and preterm Cesarean section in her first pregnancy, arterial hypertension). This case suggests using dydrogesterone as an option to prevent preeclampsia, as previously shown in a prospective randomized study. PMID- 27383902 TI - Supporting At-Risk Youth and Their Families to Manage and Prevent Diabetes: Developing a National Partnership of Medical Residency Programs and High Schools. AB - BACKGROUND: The Stanford Youth Diabetes Coaches Program (SYDCP) is a school based health program in which Family Medicine residents train healthy at-risk adolescents to become diabetes self-management coaches for family members with diabetes. This study evaluates the impact of the SYDCP when disseminated to remote sites. Additionally, this study aims to assess perceived benefit of enhanced curriculum. METHODS: From 2012-2015, 10 high schools and one summer camp in the US and Canada and five residency programs were selected to participate. Physicians and other health providers implemented the SYDCP with racial/ethnic minority students from low-income communities. Student coaches completed pre- and posttest surveys which included knowledge, health behavior, and psychosocial asset questions (i.e., worth and resilience), as well as open-ended feedback questions. T-test pre-post comparisons were used to determine differences in knowledge and psychosocial assets, and open and axial coding methods were used to analyze qualitative data. RESULTS: A total of 216 participating high school students completed both pre-and posttests, and 96 nonparticipating students also completed pre- and posttests. Student coaches improved from pre- to posttest significantly on knowledge (p<0.005 in 2012-13, 2014 camp, and 2014-15); worth (p<0.1 in 2014-15); problem solving (p<0.005 in 2014 camp and p<0.1 in 2014-15); and self-efficacy (p<0.05 in 2014 camp). Eighty-two percent of student coaches reported that they considered making a behavior change to improve their own health as a result of program participation. Qualitative feedback themes included acknowledgment of usefulness and relevance of the program, appreciation for physician instructors, knowledge gain, pride in helping family members, improved relationships and connectedness with family members, and lifestyle improvements. CONCLUSION: Overall, when disseminated, this program can increase health knowledge and some psychosocial assets of at-risk youth and holds promise to empower these youth with health literacy and encourage them to adopt healthy behaviors. PMID- 27383903 TI - Narrowing the Zero-Field Tunneling Resonance by Decreasing the Crystal Symmetry of Mn12 Acetate. AB - We report the discovery of a less symmetric crystalline phase of Mn12 acetate, a triclinic phase, resulting from recrystallizing the original tetragonal phase reported by Lis in acetonitrile and toluene. This new phase exhibits the same structure of Mn12 acetate clusters and the same positions of tunneling resonances on the magnetic field as the conventional tetragonal phase. However, the width of the zero-field resonance is at least 1 order of magnitude smaller-can be as low as 50 Oe-indicating very small inhomogeneous broadening due to dipolar and nuclear fields. PMID- 27383904 TI - 3D Visualization of the Iron Oxidation State in FeO/Fe3O4 Core-Shell Nanocubes from Electron Energy Loss Tomography. AB - The physicochemical properties used in numerous advanced nanostructured devices are directly controlled by the oxidation states of their constituents. In this work we combine electron energy-loss spectroscopy, blind source separation, and computed tomography to reconstruct in three dimensions the distribution of Fe(2+) and Fe(3+) ions in a FeO/Fe3O4 core/shell cube-shaped nanoparticle with nanometric resolution. The results highlight the sharpness of the interface between both oxides and provide an average shell thickness, core volume, and average cube edge length measurements in agreement with the magnetic characterization of the sample. PMID- 27383907 TI - Factors Controlling the Reactivity and Selectivity of the Diels-Alder Reactions Involving 1,2-Azaborines. AB - The factors controlling the reactivity and endo/exo selectivity of the Diels Alder reactions involving 1,2-azaborines have been computationally explored within the density functional theory framework. It is found that the AlCl3 catalyzed [4 + 2]-cycloaddition reaction between these dienes and N methylmaleimide proceeds concertedly and leads almost exclusively to the corresponding endo cycloadduct, which is in good agreement with previous experimental observations. In addition, the effect of the substituent directly attached to the boron atom of the 1,2-azaborine on the process is also analyzed in detail. To this end, the combination of the activation strain model of reactivity and the energy decomposition analysis methods has been applied to gain a quantitative understanding into the origins of the endo selectivity of the process as well as the influence of the boron and nitrogen substituent on the barrier heights of the transformations. PMID- 27383905 TI - Quantifying mammalian genomic DNA hydroxymethylcytosine content using solid-state nanopores. AB - 5-hydroxymethylcytosine (5 hmC), the oxidized form of 5-methylcytosine (5 mC), is a base modification with emerging importance in biology and disease. However, like most epigenetic elements, it is transparent to many conventional genetic techniques and is thus challenging to probe. Here, we report a rapid solid-state nanopore assay that is capable of resolving 5 hmC with high specificity and sensitivity and demonstrate its utility in assessing global modification abundance in genomic DNA. PMID- 27383908 TI - ADAMTS5 promotes murine adipogenesis and visceral adipose tissue expansion. AB - Enhanced expression of the aggrecanase ADAMTS5 (A Disintegrin And Metalloproteinase with Thrombospondin type 1 motifs; member 5) has been observed in adipose tissue (AT) of obese rodents. Here, we have investigated the role of ADAMTS5 in adipogenesis, AT expansion and associated angiogenesis. In vitro differentiation of precursor cells into mature adipocytes was studied using murine embryonic fibroblasts (MEF) derived from wild-type (Adamts5(+/+)) and ADAMTS5 deficient (Adamts5(-/-)) mice, or 3T3-F442A preadipocytes with stable gene silencing of Adamts5. De novo adipogenesis was monitored by injection of 3T3 F442A cells with or without Adamts5 knockdown in Nude mice. Furthermore, Adamts5(+/+)and Adamts5(-/-) mice were kept on a high-fat diet (HFD) to monitor AT development. Adamts5(-/-) MEF, as well as 3T3-F442A preadipocytes with Adamts5 knockdown, showed significantly reduced differentiation as compared to control cells. In mice, de novo formed fat pads arising from 3T3-F442A cells with Adamts5 knockdown were significantly smaller as compared to controls. After 15 or 25 weeks on HFD, total body weight and subcutaneous AT weight were similar for Adamts5(+/+) and Adamts5(-/-) mice, but visceral/gonadal fat mass was significantly lower for Adamts5(-/-) mice. These data were confirmed by magnetic resonance imaging. In addition, the blood vessel density in adipose tissue was higher for Adamts5(-/-) mice kept on HFD. In conclusion, our data support the concept that ADAMTS5 promotes adipogenesis in vitro and in vivo, as well as development of visceral AT and associated angiogenesis in mice kept on HFD. PMID- 27383909 TI - Operational conditions for successful partial nitrification in a sequencing batch reactor (SBR) based on process kinetics. AB - The objective of this study is to analyze the factors affecting the performance of partial nitrification in a sequencing batch reactor (SBR) using kinetic models. During the 4-month operation, dissolved oxygen (DO) and influent ammonia concentration were selected as operating variables to evaluate nitrite accumulation. Stable partial nitrification was observed with two conditions, influent ammonia concentration of 190 mg N/L and a DO of 0.6-3.0 mg/L as well as influent ammonia concentration of 100 mg N/L and a DO of 0.15-2.0 mg/L with intermittent aeration. At a DO of 0.6-3.0 mg O2/L and influent ammonia concentration of 90 mg N/L, nitrite-oxidizing bacteria growth was not suppressed. Kinetic parameters were determined or estimated with batch tests and model simulation. The kinetic model predicted the SBR performance well. PMID- 27383910 TI - Porous Silicon and Polymer Nanocomposites for Delivery of Peptide Nucleic Acids as Anti-MicroRNA Therapies. AB - Self-assembled polymer/porous silicon nanocomposites overcome intracellular and systemic barriers for in vivo application of peptide nucleic acid (PNA) anti microRNA therapeutics. Porous silicon (PSi) is leveraged as a biodegradable scaffold with high drug-cargo-loading capacity. Functionalization with a diblock polymer improves PSi nanoparticle colloidal stability, in vivo pharmacokinetics, and intracellular bioavailability through endosomal escape, enabling PNA to inhibit miR-122 in vivo. PMID- 27383911 TI - Neural networks within multi-core optic fibers. AB - Hardware implementation of artificial neural networks facilitates real-time parallel processing of massive data sets. Optical neural networks offer low volume 3D connectivity together with large bandwidth and minimal heat production in contrast to electronic implementation. Here, we present a conceptual design for in-fiber optical neural networks. Neurons and synapses are realized as individual silica cores in a multi-core fiber. Optical signals are transferred transversely between cores by means of optical coupling. Pump driven amplification in erbium-doped cores mimics synaptic interactions. We simulated three-layered feed-forward neural networks and explored their capabilities. Simulations suggest that networks can differentiate between given inputs depending on specific configurations of amplification; this implies classification and learning capabilities. Finally, we tested experimentally our basic neuronal elements using fibers, couplers, and amplifiers, and demonstrated that this configuration implements a neuron-like function. Therefore, devices similar to our proposed multi-core fiber could potentially serve as building blocks for future large-scale small-volume optical artificial neural networks. PMID- 27383912 TI - The adhesion GPCR latrophilin - a novel signaling cascade in oriented cell division and anterior-posterior polarity. AB - Although several signaling pathways in oriented cell division have been well characterized such as delta/notch inductions or wnt/frizzled-based anterior posterior polarity, there is strong evidence for additional signal pathways controlling early anterior-posterior polarity decisions. The homolog of the adhesion G protein-coupled receptor latrophilin, LAT-1 has been identified as a receptor essential for oriented cell division in an anterior-posterior direction of specific blastomeres in the early C. elegans embryo. We recently conducted a study aiming at clarifying the signals involved in LAT-1 function. We identified a Gs protein/adenylyl cyclase/cAMP pathway in vitro and demonstrated its physiological relevance in oriented cell division. By interaction with a Gs protein LAT-1 elevates cAMP levels. These data indicate that G-protein signaling in oriented cell division is not solely GPCR-independent. This commentary will discuss our findings in the context of the current knowledge of mechanisms controlling oriented cell division and anterior-posterior polarity. Further, we identify open questions which need to be addressed in the future. PMID- 27383914 TI - Osteoarthritis: Bone as an imaging biomarker and treatment target in OA. PMID- 27383915 TI - Rheumatoid arthritis: Glucocorticoid therapy and body composition. PMID- 27383916 TI - Paediatric rheumatology: Novel Treg cell subset discovered in JIA. PMID- 27383913 TI - Macrophage heterogeneity in the context of rheumatoid arthritis. AB - Macrophages are very important in the pathogenesis of rheumatoid arthritis (RA). The increase in the number of sublining macrophages in the synovium is an early hallmark of active rheumatic disease, and high numbers of macrophages are a prominent feature of inflammatory lesions. The degree of synovial macrophage infiltration correlates with the degree of joint erosion, and depletion of these macrophages from inflamed tissue has a profound therapeutic benefit. Research has now uncovered an unexpectedly high level of heterogeneity in macrophage origin and function, and has emphasized the role of environmental factors in their functional specialization. Although the heterogeneous populations of macrophages in RA have not been fully characterized, preliminary results in mouse models of arthritis have contributed to our understanding of the phenotype and ontogeny of synovial macrophages, and to deciphering the properties of monocyte-derived infiltrating and tissue-resident macrophages. Elucidating the molecular mechanisms that drive polarization of macrophages towards proinflammatory or anti inflammatory phenotypes could lead to identification of signalling pathways that inform future therapeutic strategies. PMID- 27383917 TI - Lupus nephritis: NRF2, a novel target in steroid-refractory LN? PMID- 27383918 TI - Understanding Voltage Decay in Lithium-Rich Manganese-Based Layered Cathode Materials by Limiting Cutoff Voltage. AB - The effect of the cutoff voltages on the working voltage decay and cyclability of the lithium-rich manganese-based layered cathode (LRMO) was investigated by electrochemical measurements, electrochemical impedance spectroscopy, ex situ X ray diffraction, transmission electron microscopy, and energy dispersive spectroscopy line scan technologies. It was found that both lower (2.0 V) and upper (4.8 V) cutoff voltages cause severe voltage decay with cycling due to formation of the spinel phase and migration of the transition metals inside the particles. Appropriate cutoff voltage between 2.8 and 4.4 V can effectively inhibit structural variation as the electrode demonstrates 92% capacity retention and indiscernible working voltage decay over 430 cycles. The results also show that phase transformation not only on high charge voltage but also on low discharge voltage should be addressed to obtain highly stable LRMO materials. PMID- 27383919 TI - Providing Oral Nutrition to Women in Labor: American College of Nurse-Midwives. AB - Historically, oral intake for women during labor has been limited to nothing by mouth or clear liquids only. These restrictions are based on the risk of aspiration during or after the administration of general anesthesia. While aspiration can be life threatening, older methods of anesthesia are rarely used in current intrapartum care, and evidence is inconclusive that withholding oral nutrition reduces the risk of gastric aspiration. Additionally, withholding oral nutrition may result in the development of ketosis and may potentially contribute to a woman's stress and dissatisfaction with the birth experience. The purpose of this Clinical Bulletin is to review the evidence related to this practice and provide recommendations to promote informed, shared decision making regarding oral intake during labor with women at low risk for gastric aspiration. PMID- 27383920 TI - Enantioselective synthesis of fluorinated branched allylic compounds via Ir catalyzed allylations of functionalized fluorinated methylene derivatives. AB - Enantioselective introduction of the functionalized monofluorinated methylenes into the allylic fragment under Ir catalysis has been realized, which gave the fluorinated branched allyl products in good to high yields with excellent regio- and enantioselectivities. PMID- 27383921 TI - Photoinduced Charge Separation in the Carbon Nano-Onion C60@C240. AB - The double-shell fullerene C60@C240 formed by inclusion of C60 into C240 is the smallest stable carbon nano-onion. In this article, we analyze in detail the character of the excited states of C60@C240 in terms of exciton localization and charge transfer between the inner and outer shells. The unique structure of the buckyonion leads to a large electrostatic stabilization of charge-separated (CS) states in the C60@C240. As a result, the CS states C60(+)@C240(-) lie in the same region of the electronic spectrum (2.4-2.6 eV) as strongly absorbing locally excited states and, therefore, can be effectively populated. The CS states C60( )@C240(+) are found to be 0.5 eV higher in energy than the CS states C60(+)@C240( ). Unlike the situation observed in donor-acceptor systems, the energies of the CS states in C60@C240 do not practically depend on the environment polarity. This leads to exceptionally small reorganization energies for electron transfer between the shells. Electronic couplings for photoinduced charge-separation and charge-recombination processes are calculated. The absolute rate of the formation of the CS state C60(+)@C240(-) is estimated at ~4 ps(-1). The electronic features found in C60@C240 are likely to be shared by other carbon nano-onions. PMID- 27383922 TI - Ambulatory and short-burst oxygen for interstitial lung disease. AB - BACKGROUND: A large subgroup of people with interstitial lung disease (ILD) are normoxic at rest, but rapidly desaturate on exertion. This can limit exercise capacity and worsen dyspnoea. The use of ambulatory or short-burst oxygen when mobilising or during other activities, may improve exercise capacity and relieve dyspnoea. OBJECTIVES: To determine the effects of ambulatory and short-burst oxygen therapy, separately, on exercise capacity, dyspnoea and quality of life in people who have interstitial lung disease (ILD), particularly those with idiopathic pulmonary fibrosis (IPF). SEARCH METHODS: We conducted searches in the Cochrane Airways Group Specialised Register (all years to May 2016), Cochrane Central Register of Controlled Trials (CENTRAL) (all years to May 2016), MEDLINE (Ovid) (1950 to 4th May 2016) and EMBASE (Ovid) (1974 to 4th May 2016). We also searched the reference lists of relevant studies, international clinical trial registries and respiratory conference abstracts for studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs that compared ambulatory or short-burst oxygen with a control group in people with ILD of any origin. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion and assessed risk of bias in the included studies. We extracted data from included studies using a prepared checklist, including study characteristics and results. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to assess the quality of the included studies. MAIN RESULTS: Three studies (including 98 participants, all of whom had IPF) met the inclusion criteria of this review. These studies were conducted in hospital respiratory physiology laboratories. Two studies did not demonstrate any beneficial effect of supplemental oxygen on exercise capacity or exertional dyspnoea. Neither of these studies titrated oxygen requirements to prevent ongoing exertional desaturation. One study showed an increase in exercise capacity as assessed by endurance time with supplemental oxygen. We did not identify any studies that examined the effect of ambulatory oxygen on health related quality of life, survival, costs or time to exacerbation or hospitalisation. No study reported any adverse events. The quality of evidence for all three studies, as assessed by GRADE criteria, was low. AUTHORS' CONCLUSIONS: This review found no evidence to support or refute the use of ambulatory or short burst oxygen in ILD due to the limited number of included studies and data. Further research is needed to examine the role of this treatment. PMID- 27383923 TI - Occurrence of artificial sweeteners in human liver and paired blood and urine samples from adults in Tianjin, China and their implications for human exposure. AB - In this study, acesulfame (ACE), saccharin (SAC) and cyclamate (CYC) were found in all paired urine and blood samples collected from healthy adults, with mean values of 4070, 918 and 628 ng mL(-1), respectively, in urine and 9.03, 20.4 and 0.72 ng mL(-1), respectively, in blood. SAC (mean: 84.4 ng g(-1)) and CYC (4.29 ng g(-1)) were detectable in all liver samples collected from liver cancer patients, while ACE was less frequently detected. Aspartame (ASP) was not found in any analyzed human sample, which can be explained by the fact that this chemical metabolized rapidly in the human body. Among all adults, significantly positive correlations between SAC and CYC levels were observed (p < 0.001), regardless of human matrices. Nevertheless, no significant correlations between concentrations of SAC (or CYC) and ACE were found in any of the human matrices. Our results suggest that human exposure to SAC and CYC is related, whereas ACE originates from a discrete source. Females (or young adults) were exposed to higher levels of SAC and CYC than males (or elderly). The mean renal clearance of SAC was 730 mL per day per kg in adults, which was significantly (p < 0.001) lower than those for CYC (10 800 mL per day per kg) and ACE (10 300 mL per day per kg). The average total daily intake of SAC and ACE was 9.27 and 33.8 MUg per kg bw per day, respectively. PMID- 27383924 TI - Fluorophore exchange kinetics in block copolymer micelles with varying solvent fluorophore and solvent-polymer interactions. AB - Fluorescence spectroscopy was employed to characterize the kinetics of guest exchange in diblock copolymer micelles composed of poly(ethylene oxide-b-epsilon caprolactone) (PEO-PCL) diblock copolymers in water/tetrahydrofuran (THF) mixtures which encapsulated fluorophores. The solvent composition (THF content) of the micelle solution was varied as a means of modulating the strength of interactions between the fluorophore and solvent as well as between the micelle core and solvent. A donor-acceptor fluorophore pair was employed consisting of 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO, the donor) and 1,1'-dioctadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI, the acceptor). Through the process of Forster resonance energy transfer (FRET), energy was transferred from the donor to acceptor when the fluorophores were in close proximity. A micelle solution containing DiO was mixed with a micelle solution containing DiI at t = 0, and the emission spectra of the mixed solution were monitored over time (at an excitation wavelength optimized for the donor). In micelle solutions containing 5 and 10 vol% THF in the bulk solvent, an increase in the acceptor peak intensity maximum occurred over time in the post-mixed solution, accompanied by a decrease in the donor peak intensity maximum, indicating the presence of energy transfer from the donor to the acceptor. At long times, the FRET ratios (acceptor peak intensity divided by the sum of the acceptor and donor peak intensities) were indistinguishable from that determined from pre-mixed micelle solutions of the same THF content (in pre-mixed solutions, DiO and DiI were encapsulated within the same micelle cores). In the micelle solution containing 20 vol% THF, the fluorophore exchange process occurred too quickly to be observed (the FRET ratios measured from the solutions mixed at t = 0 were commensurate to that measured from the pre-mixed solution). A time constant describing the guest exchange process was extracted from the time-dependence of the FRET ratio through fit of an exponential decay. An increase in the THF content in the micelle solution resulted in a decrease in the time constant, and the time constant varied over five orders of magnitude as the THF content was varied from 5-20 vol%. PMID- 27383925 TI - Corticosteroids for the prevention of ventilator-induced lung injury? PMID- 27383926 TI - Multiple calcified nodules. PMID- 27383927 TI - Choosing wisely between randomized controlled trials and observational designs in studies about interventions. PMID- 27383928 TI - Pre-treatment with dexamethasone attenuates experimental ventilator-induced lung injury. AB - OBJECTIVE: To evaluate the effects that administering dexamethasone before the induction of ventilator-induced lung injury (VILI) has on the temporal evolution of that injury. METHODS: Wistar rats were allocated to one of three groups: pre VILI administration of dexamethasone (dexamethasone group); pre-VILI administration of saline (control group); or ventilation only (sham group). The VILI was induced by ventilation at a high tidal volume. Animals in the dexamethasone and control groups were euthanized at 0, 4, 24, and 168 h after VILI induction. We analyzed arterial blood gases, lung edema, cell counts (total and differential) in the BAL fluid, and lung histology. RESULTS: At 0, 4, and 24 h after VILI induction, acute lung injury (ALI) scores were higher in the control group than in the sham group (p < 0.05). Administration of dexamethasone prior to VILI induction decreased the severity of the lung injury. At 4 h and 24 h after induction, the ALI score in the dexamethasone group was not significantly different from that observed for the sham group and was lower than that observed for the control group (p < 0.05). Neutrophil counts in BAL fluid were increased in the control and dexamethasone groups, peaking at 4 h after VILI induction (p < 0.05). However, the neutrophil counts were lower in the dexamethasone group than in the control group at 4 h and 24 h after induction (p < 0.05). Pre-treatment with dexamethasone also prevented the post-induction oxygenation impairment seen in the control group. CONCLUSIONS: Administration of dexamethasone prior to VILI induction attenuates the effects of the injury in Wistar rats. The molecular mechanisms of such injury and the possible clinical role of corticosteroids in VILI have yet to be elucidated. OBJETIVO: Avaliar os efeitos da administracao de dexametasona antes da inducao de lesao pulmonar induzida por ventilacao mecanica (LPIVM) na evolucao temporal dessa lesao. METODOS: Ratos Wistar foram alocados em um dos tres grupos: administracao de dexametasona pre-LPIVM (grupo dexametasona); administracao de salina pre-LPIVM (grupo controle); e somente ventilacao (grupo sham). A LPIVM foi realizada por ventilacao com volume corrente alto. Os animais dos grupos dexametasona e controle foram sacrificados em 0, 4, 24 e 168 h apos LPIVM. Analisamos gasometria arterial, edema pulmonar, contagens de celulas (totais e diferenciais) no lavado broncoalveolar e histologia de tecido pulmonar. RESULTADOS: Em 0, 4 e 24 h apos LPIVM, os escores de lesao pulmonar aguda (LPA) foram maiores no grupo controle que no grupo sham (p < 0,05). A administracao de dexametasona antes da LPIVM reduziu a gravidade da lesao pulmonar. Em 4 e 24 h apos a inducao, o escore de LPA no grupo dexametasona nao foi significativamente diferente daquele observado no grupo sham e foi menor que o observado no grupo controle (p < 0,05). As contagens de neutrofilos no lavado broncoalveolar estavam aumentadas nos grupos controle e dexametasona, com pico em 4 h apos LPIVM (p < 0,05). Entretanto, as contagens de neutrofilos foram menores no grupo dexametasona que no grupo controle em 4 e 24 h apos LPIVM (p < 0,05). O pre tratamento com dexametasona tambem impediu o comprometimento da oxigenacao apos a inducao visto no grupo controle. CONCLUSOES: A administracao de dexametasona antes de LPIVM atenua os efeitos da lesao em ratos Wistar. Os mecanismos moleculares dessa lesao e o possivel papel clinico dos corticosteroides na LPIVM ainda precisam ser elucidados. PMID- 27383929 TI - Evaluating bronchodilator response in pediatric patients with post-infectious bronchiolitis obliterans: use of different criteria for identifying airway reversibility. AB - OBJECTIVE: Post-infectious bronchiolitis obliterans (PIBO) is a clinical entity that has been classified as constrictive, fixed obstruction of the lumen by fibrotic tissue. However, recent studies using impulse oscillometry have reported bronchodilator responses in PIBO patients. The objective of this study was to evaluate bronchodilator responses in pediatric PIBO patients, comparing different criteria to define the response. METHODS: We evaluated pediatric patients diagnosed with PIBO and treated at one of two pediatric pulmonology outpatient clinics in the city of Porto Alegre, Brazil. Spirometric parameters were measured in accordance with international recommendations. RESULTS: We included a total of 72 pediatric PIBO patients. The mean pre- and post-bronchodilator values were clearly lower than the reference values for all parameters, especially FEF25-75%. There were post-bronchodilator improvements. When measured as mean percent increases, FEV1 and FEF25-75%, improved by 11% and 20%, respectively. However, when the absolute values were calculated, the mean FEV1 and FEF25-75% both increased by only 0.1 L. We found that age at viral aggression, a family history of asthma, and allergy had no significant effects on bronchodilator responses. CONCLUSIONS: Pediatric patients with PIBO have peripheral airway obstruction that is responsive to treatment but is not completely reversible with a bronchodilator. The concept of PIBO as fixed, irreversible obstruction does not seem to apply to this population. Our data suggest that airway obstruction is variable in PIBO patients, a finding that could have major clinical implications. OBJETIVO: A bronquiolite obliterante pos-infecciosa (BOPI) e uma entidade clinica que tem sido classificada como obstrucao fixa e constritiva do lumen por tecido fibrotico. Entretanto, estudos recentes utilizando oscilometria de impulso relataram resposta ao broncodilatador em pacientes com BOPI. O objetivo deste estudo foi avaliar a resposta broncodilatadora em pacientes pediatricos com BOPI, comparando criterios diferentes para a definicao da resposta. METODOS: Foram avaliados pacientes pediatricos com diagnostico de BOPI tratados em um de dois ambulatorios de pneumologia pediatrica na cidade de Porto Alegre (RS). Parametros espirometricos foram medidos de acordo com recomendacoes internacionais. RESULTADOS: Foram incluidos 72 pacientes pediatricos com BOPI no estudo. As medias dos valores pre- e pos-broncodilatador foram claramente inferiores aos valores de referencia para todos os parametros, especialmente FEF25-75%. Houve uma melhora pos-broncodilatador. Quando medidos como aumentos percentuais medios, VEF1 e FEF25-75% melhoraram em 11% e 20%, respectivamente. Entretanto, quando os valores absolutos foram calculados, as medias de VEF1 e FEF25-75% aumentaram somente em 0,1 l. Verificamos que a idade da agressao viral, historia familiar de asma e alergia nao tiveram efeitos significativos na resposta ao broncodilatador. CONCLUSOES: Pacientes pediatricos com BOPI tem uma obstrucao das vias aereas perifericas que responde ao tratamento, mas nao uma reversao completa com o broncodilatador. O conceito de BOPI como obstrucao fixa e irreversivel parece nao se aplicar a essa populacao. Nossos dados sugerem que a obstrucao de vias aereas em pacientes com BOPI e variavel, e esse achado pode ter importantes implicacoes clinicas. PMID- 27383930 TI - Risk factors for cardiovascular disease in patients with COPD: mild-to-moderate COPD versus severe-to-very severe COPD. AB - OBJECTIVE: To assess and compare the prevalence of comorbidities and risk factors for cardiovascular disease (CVD) in COPD patients according to disease severity. METHODS: The study included 25 patients with mild-to-moderate COPD (68% male; mean age, 65 +/- 8 years; mean FEV1, 73 +/- 15% of predicted) and 25 with severe to-very severe COPD (males, 56%; mean age, 69 +/- 9 years; mean FEV1, 40 +/- 18% of predicted). Comorbidities were recorded on the basis of data obtained from medical charts and clinical evaluations. Comorbidities were registered on the basis of data obtained from medical charts and clinical evaluations. The Charlson comorbidity index was calculated, and the Hospital Anxiety and Depression Scale (HADS) score was determined. RESULTS: Of the 50 patients evaluated, 38 (76%) had been diagnosed with at least one comorbidity, 21 (42%) having been diagnosed with at least one CVD. Twenty-four patients (48%) had more than one CVD. Eighteen (36%) of the patients were current smokers, 10 (20%) had depression, 7 (14%) had dyslipidemia, and 7 (14%) had diabetes mellitus. Current smoking, depression, and dyslipidemia were more prevalent among the patients with mild-to-moderate COPD than among those with severe-to-very severe COPD (p < 0.001, p = 0.008, and p = 0.02, respectively). The prevalence of high blood pressure, diabetes mellitus, alcoholism, ischemic heart disease, and chronic heart failure was comparable between the two groups. The Charlson comorbidity index and HADS scores did not differ between the groups. CONCLUSIONS: Comorbidities are highly prevalent in COPD, regardless of its severity. Certain risk factors for CVD, themselves classified as diseases (including smoking, dyslipidemia, and depression), appear to be more prevalent in patients with mild-to-moderate COPD. OBJETIVO: Avaliar e comparar a prevalencia de comorbidades e de fatores de risco de doenca cardiovascular (DCV) em pacientes com DPOC de acordo com a gravidade da doenca. METODOS: O estudo incluiu 25 pacientes com DPOC leve/moderada (homens: 68%; media de idade: 65 +/- 8 anos; media de VEF1: 73 +/- 15% do previsto) e 25 com DPOC grave/muito grave (homens: 56%; media de idade: 69 +/- 9 anos; media de VEF1, 40 +/- 18% do previsto). As comorbidades foram registradas com base nos dados dos prontuarios medicos e avaliacoes clinicas. O indice de comorbidades de Charlson foi calculado, e a pontuacao na Hospital Anxiety and Depression Scale (HADS) foi determinada. RESULTADOS: Dos 50 pacientes avaliados, 38 (76%) receberam diagnostico de pelo menos uma comorbidade, sendo que 21 (42%) receberam diagnostico de pelo menos uma DCV. Vinte e quatro pacientes (48%) apresentavam mais de uma DCV. Dezoito pacientes (36%) eram fumantes, 10 (20%) tinham depressao, 7 (14%) apresentavam dislipidemia, e 7 (14%) tinham diabetes mellitus. Tabagismo atual, depressao e dislipidemia foram mais prevalentes nos pacientes com DPOC leve/moderada que naqueles com DPOC grave/muito grave (p < 0,001, p = 0,008 e p = 0,02, respectivamente). A prevalencia de pressao arterial elevada, diabetes mellitus, alcoolismo, doenca isquemica do coracao e insuficiencia cardiaca cronica foi semelhante nos dois grupos. O indice de comorbidades de Charlson e a pontuacao na HADS nao diferiram entre os grupos. CONCLUSOES: Comorbidades sao muito prevalentes na DPOC, independentemente da gravidade da doenca. Certos fatores de risco de DCV, eles proprios considerados doencas (incluindo tabagismo, dislipidemia e depressao), parecem ser mais prevalentes nos pacientes com DPOC leve/moderada. PMID- 27383931 TI - Robotic pulmonary lobectomy for lung cancer treatment: program implementation and initial experience. AB - OBJECTIVE: To describe the implementation of a robotic thoracic surgery program at a public tertiary teaching hospital and to analyze its initial results. METHODS: This was a planned interim analysis of a randomized clinical trial aimed at comparing video-assisted thoracoscopic surgery and robotic surgery in terms of the results obtained after pulmonary lobectomy. The robotic surgery program developed at the Instituto do Cancer do Estado de Sao Paulo, in the city of Sao Paulo, Brazil, is a multidisciplinary initiative involving various surgical specialties, as well as anesthesiology, nursing, and clinical engineering teams. In this analysis, we evaluated the patients included in the robotic lobectomy arm of the trial during its first three months (from April to June of 2015). RESULTS: Ten patients were included in this analysis. There were eight women and two men. The mean age was 65.1 years. All of the patients presented with peripheral tumors. We performed right upper lobectomy in four patients, right lower lobectomy in four, and left upper lobectomy in two. Surgical time varied considerably (range, 135-435 min). Conversion to open surgery or video-assisted thoracoscopic surgery was not necessary in any of the cases. Intraoperative complications were not found. Only the first patient required postoperative transfer to the ICU. There were no deaths or readmissions within the first 30 days after discharge. The only postoperative complication was chest pain (grade 3), in two patients. Pathological examination revealed complete tumor resection in all cases. CONCLUSIONS: When there is integration and proper training of all of the teams involved, the implementation of a robotic thoracic surgery program is feasible and can reduce morbidity and mortality. OBJETIVO: Descrever a implantacao de um programa de cirurgia toracica robotica em um hospital terciario publico universitario e analisar seus resultados iniciais. METODOS: Este estudo e uma analise interina planejada de um ensaio clinico aleatorizado cujo objetivo e comparar resultados da lobectomia pulmonar por videotoracoscopia com a robotica. O programa de cirurgia robotica do Instituto do Cancer do Estado de Sao Paulo, localizado na cidade de Sao Paulo (SP), foi uma iniciativa multidisciplinar que envolveu diversas especialidades cirurgicas e equipes de anestesia, enfermagem e engenharia clinica. Nesta analise, avaliamos os pacientes incluidos no braco lobectomia robotica durante os primeiros tres meses do estudo (de abril a junho de 2015). RESULTADOS: Dez pacientes foram incluidos nesta analise. Eram oito mulheres e dois homens. A media de idade foi de 65,1 anos. Todos apresentavam tumores perifericos. Foram realizadas lobectomia superior direita, em quatro pacientes; lobectomia inferior direita, em quatro; e lobectomia superior esquerda, em dois. Os tempos cirurgicos variaram bastante (variacao, 135-435 min). Nao foi necessaria a conversao para tecnica aberta ou videotoracoscopica em nenhum paciente. Nao foram observadas complicacoes intraoperatorias. Apenas o primeiro paciente foi encaminhado a UTI no pos-operatorio. Nao houve mortalidade nem reinternacoes em 30 dias apos a alta. A unica complicacao pos-operatoria observada foi dor toracica (grau 3), em dois pacientes. O exame anatomopatologico revelou a resseccao completa do tumor em todos os casos. CONCLUSOES: A implantacao de um programa de cirurgia toracica robotica, quando ha integracao e treinamento adequado de todas as equipes envolvidas, e factivel e pode reduzir a morbidade e a mortalidade. PMID- 27383932 TI - Bronchoscopic diagnostic procedures and microbiological examinations in proving endobronchial tuberculosis. AB - OBJECTIVE: To determine the proportional distribution of endobronchial tuberculosis (EBTB) subtypes and to evaluate the types of bronchoscopic diagnostic procedures that can prove granulomatous inflammation. METHODS: This was a retrospective study of 18 HIV-negative patients with biopsy-proven EBTB treated between 2010 and 2014. RESULTS: The most common EBTB subtypes, as classified by the bronchoscopic features, were tumorous and granular (in 22.2% for both). Sputum smear microscopy was performed in 11 patients and was positive for AFB in 4 (36.3%). Sputum culture was also performed in 11 patients and was positive for Mycobacterium tuberculosis in 10 (90.9%). Smear microscopy of BAL fluid (BALF) was performed in 16 patients and was positive for AFB in 10 (62.5%). Culture of BALF was also performed in 16 patients and was positive for M. tuberculosis in 15 (93.7%). Culture of BALF was positive for M. tuberculosis in 93.7% of the 16 patients tested. Among the 18 patients with EBTB, granulomatous inflammation was proven by the following bronchoscopic diagnostic procedures: bronchial mucosal biopsy, in 8 (44.4%); bronchial brushing, in 7 (38.8%); fine needle aspiration biopsy, in 2 (11.1%); and BAL, in 2 (11.1%). Bronchial anthracofibrosis was observed in 5 (27.7%) of the 18 cases evaluated. CONCLUSIONS: In our sample of EBTB patients, the most common subtypes were the tumorous and granular subtypes. We recommend that sputum samples and BALF samples be evaluated by smear microscopy for AFB and by culture for M. tuberculosis, which could increase the rates of early diagnosis of EBTB. We also recommend that bronchial brushing be employed together with other bronchoscopic diagnostic procedures in patients suspected of having EBTB. OBJETIVO: Determinar a distribuicao proporcional dos subtipos de tuberculose endobronquica (TBEB) e avaliar os tipos de procedimentos diagnosticos broncoscopicos que podem revelar inflamacao granulomatosa. METODOS: Este foi um estudo retrospectivo com 18 pacientes HIV negativos com TBEB comprovada por biopsia tratados entre 2010 e 2014. RESULTADOS: Os subtipos mais comuns de TBEB, classificados pelas caracteristicas na broncoscopia, foram tumoral e granular (em 22,2% para ambas) A baciloscopia de escarro foi realizada em 11 pacientes e foi positiva para BAAR em 4 (36,3%). A cultura de escarro tambem foi realizada em 11 pacientes e foi positiva para Mycobacterium tuberculosis em 10 (90,9%). A baciloscopia do LBA foi realizada em 16 pacientes e foi positiva para BAAR em 10 (62,5%). A cultura do LBA foi tambem realizada em 16 pacientes e foi positiva para o M. tuberculosis em 15 (93,7%). A cultura do LBA foi positiva para M. tuberculosis em 93,7% dos 16 pacientes testados. Nos 18 pacientes com TBEB, a presenca de inflamacao granulomatosa foi comprovada pelos seguintes procedimentos diagnosticos broncoscopicos: biopsia da mucosa bronquica, em 8 (44,4%); escovacao bronquica, em 7 (38,8%); puncao aspirativa por agulha fina, em 2 (11,1%); e LBA, em 2 (11,1%). Antracose/fibrose bronquica foi observada em 5 (27,7%) dos 18 casos avaliados. CONCLUSOES: Em nossa amostra de pacientes com TBEB, os subtipos mais comuns foram o tumoral e o granular. Recomendamos que amostras de escarro e do LBA sejam avaliadas por baciloscopia para BAAR e cultura de M. tuberculosis, o que poderia aumentar as taxas de diagnostico precoce de TBEB. Tambem recomendamos que a escovacao bronquica seja empregada em conjunto com outros procedimentos diagnosticos broncoscopicos em pacientes com suspeita de TBEB. PMID- 27383933 TI - Viability of gait speed test in hospitalized elderly patients. AB - OBJECTIVE: The gait speed test (GST) is a physical test that can predict falls and aid in the diagnosis of sarcopenia in the elderly. However, to our knowledge, there have been no studies evaluating its reproducibility in hospitalized elderly patients. The objective of this study was to evaluate the safety and reproducibility of the six-meter GST (6GST) in hospitalized elderly patients. METHODS: This repeated measures study involved hospitalized elderly patients (>= 60 years of age) who underwent the 6GST by the fifth day of hospitalization, were able to walk without assistance, and presented no signs of dyspnea or pain that would prevent them from performing the test. The 6GST was performed three times in sequence, with a rest period between each test, in a level corridor. Gait speed was measured in meters/second. Reproducibility was assessed by comparing the means, intraclass correlation coefficients (ICCs) and Bland-Altman plots. RESULTS: We evaluated 110 elderly patients in a total of 330 tests. All participants completed all of the tests. The comparisons between the speeds obtained during the three tests showed high ICCs and a low mean bias (Bland Altman plots). The correlation and accuracy were greatest when the mean maximum speed was compared with that obtained in the third test (1.26 +/- 0.44 m/s vs. 1.22 +/- 0.44 m/s; ICC = 0.99; p = 0.001; mean bias = 0.04; and limits of agreement = -0.27 to 0.15). CONCLUSIONS: The 6GST was proven to be safe and to have good reproducibility in this sample of hospitalized elderly patients. The third measurement seems to correspond to the maximum speed, since the first two measurements underestimated the actual performance. OBJETIVO: O teste de velocidade de marcha (TVM) e um teste fisico que pode predizer quedas e auxiliar no diagnostico de sarcopenia em idosos da comunidade. Entretanto, pelo que sabemos, nao ha estudos que avaliaram sua reprodutibilidade em idosos hospitalizados. O objetivo deste estudo foi avaliar a seguranca e a reprodutibilidade do TVM de seis metros (TVM6) em idosos hospitalizados. METODOS: Estudo com medidas repetidas envolvendo idosos hospitalizados (idade >= 60 anos) que realizaram o TVM6 ate o quinto dia de hospitalizacao, sendo capazes de andar sem auxilio e nao apresentando dispneia ou dor que os incapacitasse para a realizacao dos testes. O TVM6 foi realizado sequencialmente tres vezes, com periodo de descanso, em um corredor plano, e a velocidade de marcha foi calculada em metros/segundo. A reprodutibilidade foi avaliada pela comparacao das medias, coeficientes de correlacao intraclasse (CCI) e disposicoes graficas de Bland Altman. RESULTADOS: Foram avaliados 110 idosos avaliados com um total de 330 testes. Todos os participantes completaram todos os testes. As comparacoes entre as velocidades obtidas nos tres testes realizados indicaram CCIs elevados e vies medio baixo pela disposicao grafica de Bland-Altman. Em relacao a maior velocidade aferida, a correlacao e a precisao foram maiores quando comparadas a obtida no terceiro teste (1,26 +/- 0,44 m/s vs. 1,22 +/- 0,44 m/s; CCI = 0,99; p = 0,001; vies medio = 0,04; e limites de concordancia = -0,27 a 0,15). CONCLUSOES: O TVM6 mostrou-se seguro e teve boa reprodutibilidade nessa amostra de idosos hospitalizados. A terceira afericao parece corresponder a velocidade maxima, ja que duas primeiras subestimaram o desempenho real. PMID- 27383934 TI - The value of antibody-coated bacteria in tracheal aspirates for the diagnosis of ventilator-associated pneumonia: a case-control study. AB - OBJECTIVE: Ventilator-associated pneumonia (VAP) is the leading type of hospital acquired infection in ICU patients. The diagnosis of VAP is challenging, mostly due to limitations of the diagnostic methods available. The aim of this study was to determine whether antibody-coated bacteria (ACB) evaluation can improve the specificity of endotracheal aspirate (EA) culture in VAP diagnosis. METHODS: We conducted a diagnostic case-control study, enrolling 45 patients undergoing mechanical ventilation. Samples of EA were obtained from patients with and without VAP (cases and controls, respectively), and we assessed the number of bacteria coated with FITC-conjugated monoclonal antibodies (IgA, IgM, or IgG) or an FITC-conjugated polyvalent antibody. Using immunofluorescence microscopy, we determined the proportion of ACB among a fixed number of 80 bacteria. RESULTS: The median proportions of ACB were significantly higher among the cases (n = 22) than among the controls (n = 23)-IgA (60.6% vs. 22.5%), IgM (42.5% vs. 12.5%), IgG (50.6% vs. 17.5%), and polyvalent (75.6% vs. 33.8%)-p < 0.001 for all. The accuracy of the best cut-off points for VAP diagnosis regarding monoclonal and polyvalent ACBs was greater than 95.0% and 93.3%, respectively. CONCLUSIONS: The numbers of ACB in EA samples were higher among cases than among controls. Our findings indicate that evaluating ACB in EA is a promising tool to improve the specificity of VAP diagnosis. The technique could be cost-effective and therefore useful in low-resource settings, with the advantages of minimizing false-positive results and avoiding overtreatment. OBJETIVO: A pneumonia associada a ventilacao mecanica (PAVM) e o principal tipo de infeccao adquirida no ambiente hospitalar em pacientes em UTIs. O diagnostico de PAVM e desafiador, principalmente devido a limitacoes dos metodos diagnosticos disponiveis. O objetivo deste estudo foi determinar se a avaliacao de bacterias revestidas por anticorpos (BRA) pode melhorar a especificidade de culturas de aspirado traqueal (AT) no diagnostico de PAVM. METODOS: Estudo diagnostico caso-controle envolvendo 45 pacientes sob ventilacao mecanica. Amostras de AT foram obtidas de pacientes com e sem PAVM (casos e controles, respectivamente), e verificamos o numero de bacterias revestidas com anticorpos monoclonais conjugados com FITC (IgA, IgM ou IgG) ou anticorpo polivalente conjugado com FITC. Utilizando microscopia de imunofluorescencia, foi determinada a proporcao de BRA em um numero fixo de 80 bacterias. RESULTADOS: A mediana das proporcoes de BRA foi significativamente maior nos casos (n = 22) que nos controles (n = 23) - IgA (60,6% vs. 22,5%), IgM (42,5% vs. 12,5%), IgG (50,6% vs. 17,5%) e polivalente (75,6% vs. 33,8%) - p < 0,001 para todos. A acuracia dos melhores pontos de corte para o diagnostico de PAVM em relacao aos BRA monoclonais e polivalentes foi > 95,0% e > 93,3%, respectivamente. CONCLUSOES: O numero de BRA em amostras de AT foi maior nos casos que nos controles. Nossos achados indicam que a avaliacao de BRA no AT e uma ferramenta promissora para aumentar a especificidade do diagnostico de PAVM. A tecnica pode ser custo-efetiva e, portanto, util em locais com poucos recursos, com as vantagens de minimizar resultados falso-positivos e evitar o tratamento excessivo. PMID- 27383935 TI - Analysis of the stability of housekeeping gene expression in the left cardiac ventricle of rats submitted to chronic intermittent hypoxia. AB - Obstructive sleep apnea (OSA) has been associated with oxidative stress and various cardiovascular consequences, such as increased cardiovascular disease risk. Quantitative real-time PCR is frequently employed to assess changes in gene expression in experimental models. In this study, we analyzed the effects of chronic intermittent hypoxia (an experimental model of OSA) on housekeeping gene expression in the left cardiac ventricle of rats. Analyses via four different approaches-use of the geNorm, BestKeeper, and NormFinder algorithms; and 2 DeltaCt (threshold cycle) data analysis-produced similar results: all genes were found to be suitable for use, glyceraldehyde-3-phosphate dehydrogenase and 18S being classified as the most and the least stable, respectively. The use of more than one housekeeping gene is strongly advised. RESUMO A apneia obstrutiva do sono (AOS) tem sido associada ao estresse oxidativo e a varias consequencias cardiovasculares, tais como risco aumentado de doenca cardiovascular. A PCR quantitativa em tempo real e frequentemente empregada para avaliar alteracoes na expressao genica em modelos experimentais. Neste estudo, analisamos os efeitos da hipoxia intermitente cronica (um modelo experimental de AOS) na expressao de genes de referencia no ventriculo cardiaco esquerdo de ratos. Analises a partir de quatro abordagens - uso dos algoritmos geNorm, BestKeeper e NormFinder e analise de dados 2-DeltaCt (ciclo limiar) - produziram resultados semelhantes: todos os genes mostraram-se adequados para uso, sendo que gliceraldeido-3-fosfato desidrogenase e 18S foram classificados como o mais e o menos estavel, respectivamente. A utilizacao de mais de um gene de referencia e altamente recomendada. PMID- 27383937 TI - Etiology of primary spontaneous pneumothorax. AB - With the advent of HRCT, primary spontaneous pneumothorax has come to be better understood and managed, because its etiology can now be identified in most cases. Primary spontaneous pneumothorax is mainly caused by the rupture of a small subpleural emphysematous vesicle (designated a bleb) or of a subpleural paraseptal emphysematous lesion (designated a bulla). The aim of this pictorial essay was to improve the understanding of primary spontaneous pneumothorax and to propose a description of the major anatomical lesions found during surgery. RESUMO Com o advento da TCAR, o pneumotorax espontaneo primario passou a ser mais bem entendido e conduzido, pois sua etiologia pode ser atualmente identificada na maioria dos casos. O pneumotorax espontaneo primario tem como principal causa a rotura de uma pequena vesicula enfisematosa subpleural, denominada bleb ou de uma lesao enfisematosa parasseptal subpleural, denominada bulla. O objetivo deste ensaio pictorico foi melhorar o entendimento do pneumotorax espontaneo primario e propor uma descricao das principais lesoes anatomicas encontradas durante a cirurgia. PMID- 27383938 TI - Implications of a tracheal bronchus in a patient with thymoma. PMID- 27383936 TI - Anatomic pulmonary resection by video-assisted thoracoscopy: the Brazilian experience (VATS Brazil study). AB - OBJECTIVE: The objective of this study was to describe the results of anatomic pulmonary resections performed by video-assisted thoracoscopy in Brazil. METHODS: Thoracic surgeons (members of the Brazilian Society of Thoracic Surgery) were invited, via e-mail, to participate in the study. Eighteen surgeons participated in the project by providing us with retrospective databases containing information related to anatomic pulmonary resections performed by video-assisted thoracoscopy. Demographic, surgical, and postoperative data were collected with a standardized instrument, after which they were compiled and analyzed. RESULTS: The surgeons provided data related to a collective total of 786 patients (mean number of resections per surgeon, 43.6). However, 137 patients were excluded because some data were missing. Therefore, the study sample comprised 649 patients. The mean age of the patients was 61.7 years. Of the 649 patients, 295 (45.5%) were male. The majority-521 (89.8%)-had undergone surgery for neoplasia, which was most often classified as stage IA. The median duration of pleural drainage was 3 days, and the median hospital stay was 4 days. Of the 649 procedures evaluated, 598 (91.2%) were lobectomies. Conversion to thoracotomy was necessary in 30 cases (4.6%). Postoperative complications occurred in 124 patients (19.1%), the most common complications being pneumonia, prolonged air leaks, and atelectasis. The 30-day mortality rate was 2.0%, advanced age and diabetes being found to be predictors of mortality. CONCLUSIONS: Our analysis of this representative sample of patients undergoing pulmonary resection by video assisted thoracoscopy in Brazil showed that the procedure is practicable and safe, as well as being comparable to those performed in other countries. OBJETIVO: O objetivo deste estudo foi descrever os resultados de resseccoes pulmonares anatomicas por videotoracoscopia no Brasil. METODOS: Cirurgioes toracicos (membros da Sociedade Brasileira de Cirurgia Toracica) foram convidados, por correio eletronico, a participar do estudo. Dezoito cirurgioes participaram do projeto enviando seus bancos de dados retrospectivos referentes a resseccoes anatomicas de pulmao por videotoracoscopia. Dados demograficos, cirurgicos e pos-operatorios foram coletados em um instrumento padronizado e posteriormente compilados e analisados. RESULTADOS: Dados referentes a 786 pacientes foram encaminhados (media de 43,6 resseccoes por cirurgiao), sendo 137 excluidos por informacoes incompletas. Logo, 649 pacientes constituiram nossa populacao estudada. A media de idade dos pacientes foi de 61,7 anos, 295 eram homens (45,5%), e a maioria - 521 (89,8%) - foi submetida a cirurgia por neoplasia, mais frequentemente classificada como estadio IA. A mediana do tempo de drenagem pleural foi de 3 dias, e a do tempo de internacao, 4 dias. Dos 649 procedimentos realizados, 598 (91,2%) foram lobectomias. A taxa de conversao para toracotomia foi de 4,6% (30 casos). Complicacoes pos-operatorias ocorreram em 124 pacientes (19,1%), sendo pneumonia, escape aereo prolongado e atelectasia as mais frequentes. A mortalidade em 30 dias foi de 2,0%, tendo como preditores idade avancada e diabetes. CONCLUSOES: A casuistica brasileira mostra que as resseccoes pulmonares por cirurgia toracica videoassistida sao factiveis e seguras, alem de comparaveis aquelas de registros internacionais. PMID- 27383939 TI - Impact of long-term treatment with inhaled corticosteroids and bronchodilators on lung function in a patient with post-infectious bronchiolitis obliterans. AB - Post-infectious bronchiolitis obliterans (PIBO) is a small airways disease characterized by fixed airflow limitation. Therefore, inhaled bronchodilators and corticosteroids are not recommended as maintenance therapy options. The management of PIBO currently consists only of close monitoring of affected patients, aimed at the prevention and early treatment of pulmonary infections. In recent years, there has been an increase in the incidence of PIBO in the pediatric population. Patients with PIBO are characterized by a progressive decline in lung function, accompanied by a decrease in overall functional capacity. Here, we report the case of a relatively young man diagnosed with PIBO and followed for three years. After short- and long-term therapy with an inhaled corticosteroid/long-acting ?2 agonist combination, together with an inhaled long acting antimuscarinic, the patient showed relevant improvement of airway obstruction that had been irreversible at the time of the bronchodilator test. The lung function of the patient worsened when he interrupted the triple inhaled therapy. In addition, a 3-week pulmonary rehabilitation program markedly improved his physical performance. RESUMO A bronquiolite obliterante pos-infecciosa (BOPI) e uma doenca das pequenas vias aereas caracterizada por limitacao fixa do fluxo aereo. Portanto, os broncodilatadores e os corticosteroides inalatorios nao sao recomendados como opcoes de terapia de manutencao. Atualmente, o manejo da BOPI consiste apenas de um acompanhamento rigoroso dos pacientes afetados, visando a prevencao e ao tratamento precoce de infeccoes pulmonares. A incidencia de BOPI tem aumentado na populacao pediatrica nos ultimos anos. Os pacientes com BOPI caracterizam-se por um declinio progressivo da funcao pulmonar, associado a uma diminuicao da capacidade funcional global. Relatamos aqui o caso de um homem relativamente jovem diagnosticado com BOPI, acompanhado por tres anos. Apos terapia de curto e de longo prazo com uma combinacao de corticosteroide/?2 agonista de longa duracao inalatorios, associada a um agente antimuscarinico de longa duracao inalatorio, o paciente apresentou uma melhora relevante da obstrucao das vias aereas, a qual fora irreversivel durante o teste de broncodilatacao. A funcao pulmonar do paciente piorou quando ele interrompeu a terapia inalatoria tripla. Alem disso, um programa de reabilitacao pulmonar de tres semanas significativamente melhorou seu desempenho fisico. PMID- 27383940 TI - Reversed halo sign in invasive fungal infections. PMID- 27383941 TI - An old risk factor for COPD: rest in peace, 15. PMID- 27383942 TI - Inhalation therapy in mechanical ventilationAUTHORS' REPLYJet, ultrasonic, and mesh nebulizers an evaluation of nebulizers for better clinical outcomesHow best to deliver aerosol medications to mechanically ventilated patients. PMID- 27383943 TI - Gender differences in feelings and knowledge about stroke. AB - AIMS AND OBJECTIVES: To examine gender differences in knowledge and feelings about stroke among >=40 years old population. BACKGROUND: Knowledge of stroke is consistently found to be poor among both genders in general populations, however, it has been reported to be better among women than men. Gender differences in feelings about stroke in the general population have not been examined. DESIGN AND METHODS: Data were collected from a convenience sample using semi-structured personal interviews. Participants were representative of Israeli sub-populations aged >=40 with no history of stroke. Knowledge of stroke was studied with quantitative methods while constant comparative analysis was used for the qualitative data analysis of feelings evoked by stroke. RESULTS: One hundred and seventy-seven participants were interviewed, 79/177 (44.6%) men and 98/177 (55.4%) women. Rates of self-reported hypertension [33/79 (41.8%) men, 25/98 (25.5%) women] and current smoking [29/79 (36.7%) men, 18/98 (18.4%) women] were significantly higher in men than women. Over 50% men and women mentioned one-side sudden weakness or paralysis as a stroke symptom, however, other stroke symptoms were not recognised by most participants. Education was associated with the number of identified stroke signs. Knowledge of stroke-warning signs was better in women. The main feelings expressed by both genders were fear of dying and disability, self-concern about survival, blaming fate and self-accusation. CONCLUSION: Stroke knowledge is poor among men and women. Higher level of education is a predictor of stroke knowledge among both genders. Gender-specific differences in stroke risk factors and feelings about stroke in different sub populations should be taken into account to improve prevention of stroke through education programmes. RELEVANCE TO CLINICAL PRACTICE: Health education on stroke prevention should be tailored to population groups differing in level of education. Health promotion recommendations should be provided by nurses with regard to beliefs of both men and women regarding prevention of stroke. PMID- 27383945 TI - Photodissociation of ultracold diatomic strontium molecules with quantum state control. AB - Chemical reactions at ultracold temperatures are expected to be dominated by quantum mechanical effects. Although progress towards ultracold chemistry has been made through atomic photoassociation, Feshbach resonances and bimolecular collisions, these approaches have been limited by imperfect quantum state selectivity. In particular, attaining complete control of the ground or excited continuum quantum states has remained a challenge. Here we achieve this control using photodissociation, an approach that encodes a wealth of information in the angular distribution of outgoing fragments. By photodissociating ultracold (88)Sr2 molecules with full control of the low-energy continuum, we access the quantum regime of ultracold chemistry, observing resonant and nonresonant barrier tunnelling, matter-wave interference of reaction products and forbidden reaction pathways. Our results illustrate the failure of the traditional quasiclassical model of photodissociation and instead are accurately described by a quantum mechanical model. The experimental ability to produce well-defined quantum continuum states at low energies will enable high-precision studies of long-range molecular potentials for which accurate quantum chemistry models are unavailable, and may serve as a source of entangled states and coherent matter waves for a wide range of experiments in quantum optics. PMID- 27383944 TI - Effect of Pomegranate Hull Extract on Liver Neoplastic Changes in Rats: More than an Antioxidant. AB - Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide. The current work was designed to elucidate the molecular mechanisms underlying the antitumorigenic effect of pomegranate hull extract (PHE) in livers of rats exposed to the hepatocarcinogen diethyl nitrosamine (DENA) with emphasis on oxidative stress, proliferation, and apoptosis. Male albino rats were divided into three groups: normal control, DENA group, and PHE group. PHE was given to rats orally 3 times weekly for 10 wk, 4 wk before and 6 wk after DENA (200 mg/kg, single i.p. dose). The results indicated a prophylactic effect of PHE against neoplastic changes in the liver, which was evidenced by the decrease of tumor size, liver index, and the anti-apoptotic protein Bcl-2; and the increase of glutathione. PHE group also showed decreased expression of liver cyclin D1 and beta-catenin genes compared with DENA group. It is proved that PHE has antitumorigenic effect and could be a candidate for anticancer drugs. PMID- 27383946 TI - FDA should stand firm on stem-cell treatments. PMID- 27383947 TI - The past, present and future of the PhD thesis. PMID- 27383948 TI - Use Zika to renew focus on birth-defect research. PMID- 27383949 TI - Find the time to discuss new bioweapons. PMID- 27383961 TI - Obama's top scientist talks shrinking budgets, Donald Trump, and his biggest regret. PMID- 27383962 TI - Zika raises profile of more common birth-defect virus. PMID- 27383963 TI - Dry Amazon could see record fire season. PMID- 27383964 TI - Science academies blast US government's planned research-ethics reforms. PMID- 27383965 TI - CubeSats set for deep space - if they can hitch a ride. PMID- 27383966 TI - Clarification. PMID- 27383967 TI - Back to the thesis. PMID- 27383968 TI - What's the point of the PhD thesis? PMID- 27383969 TI - Validate personal air-pollution sensors. PMID- 27383970 TI - Let's make peer review scientific. PMID- 27383972 TI - North Africa: Stop slaughter of migrating songbirds. PMID- 27383973 TI - Project management: Food security needs social-science input. PMID- 27383974 TI - Fetal tissue: US panel risks infant and researcher lives. PMID- 27383975 TI - Expert performance: Don't undervalue the social sciences. PMID- 27383976 TI - Astrophysics: Rare data from a lost satellite. PMID- 27383977 TI - Chemical physics: Quantum control of light-induced reactions. PMID- 27383978 TI - Intestinal microbiota in health and disease. PMID- 27383979 TI - A microbial perspective of human developmental biology. AB - When most people think of human development, they tend to consider only human cells and organs. Yet there is another facet that involves human-associated microbial communities. A microbial perspective of human development provides opportunities to refine our definitions of healthy prenatal and postnatal growth and to develop innovative strategies for disease prevention and treatment. Given the dramatic changes in lifestyles and disease patterns that are occurring with globalization, we issue a call for the establishment of 'human microbial observatories' designed to examine microbial community development in birth cohorts representing populations with diverse anthropological characteristics, including those undergoing rapid change. PMID- 27383980 TI - Diet-microbiota interactions as moderators of human metabolism. AB - It is widely accepted that obesity and associated metabolic diseases, including type 2 diabetes, are intimately linked to diet. However, the gut microbiota has also become a focus for research at the intersection of diet and metabolic health. Mechanisms that link the gut microbiota with obesity are coming to light through a powerful combination of translation-focused animal models and studies in humans. A body of knowledge is accumulating that points to the gut microbiota as a mediator of dietary impact on the host metabolic status. Efforts are focusing on the establishment of causal relationships in people and the prospect of therapeutic interventions such as personalized nutrition. PMID- 27383981 TI - The microbiome and innate immunity. AB - The intestinal microbiome is a signalling hub that integrates environmental inputs, such as diet, with genetic and immune signals to affect the host's metabolism, immunity and response to infection. The haematopoietic and non haematopoietic cells of the innate immune system are located strategically at the host-microbiome interface. These cells have the ability to sense microorganisms or their metabolic products and to translate the signals into host physiological responses and the regulation of microbial ecology. Aberrations in the communication between the innate immune system and the gut microbiota might contribute to complex diseases. PMID- 27383982 TI - The microbiota in adaptive immune homeostasis and disease. AB - In the mucosa, the immune system's T cells and B cells have position-specific phenotypes and functions that are influenced by the microbiota. These cells play pivotal parts in the maintenance of immune homeostasis by suppressing responses to harmless antigens and by enforcing the integrity of the barrier functions of the gut mucosa. Imbalances in the gut microbiota, known as dysbiosis, can trigger several immune disorders through the activity of T cells that are both near to and distant from the site of their induction. Elucidation of the mechanisms that distinguish between homeostatic and pathogenic microbiota-host interactions could identify therapeutic targets for preventing or modulating inflammatory diseases and for boosting the efficacy of cancer immunotherapy. PMID- 27383983 TI - Interactions between the microbiota and pathogenic bacteria in the gut. AB - The microbiome has an important role in human health. Changes in the microbiota can confer resistance to or promote infection by pathogenic bacteria. Antibiotics have a profound impact on the microbiota that alters the nutritional landscape of the gut and can lead to the expansion of pathogenic populations. Pathogenic bacteria exploit microbiota-derived sources of carbon and nitrogen as nutrients and regulatory signals to promote their own growth and virulence. By eliciting inflammation, these bacteria alter the intestinal environment and use unique systems for respiration and metal acquisition to drive their expansion. Unravelling the interactions between the microbiota, the host and pathogenic bacteria will produce strategies for manipulating the microbiota against infectious diseases. PMID- 27383984 TI - Microbiome-wide association studies link dynamic microbial consortia to disease. AB - Rapid advances in DNA sequencing, metabolomics, proteomics and computational tools are dramatically increasing access to the microbiome and identification of its links with disease. In particular, time-series studies and multiple molecular perspectives are facilitating microbiome-wide association studies, which are analogous to genome-wide association studies. Early findings point to actionable outcomes of microbiome-wide association studies, although their clinical application has yet to be approved. An appreciation of the complexity of interactions among the microbiome and the host's diet, chemistry and health, as well as determining the frequency of observations that are needed to capture and integrate this dynamic interface, is paramount for developing precision diagnostics and therapies that are based on the microbiome. PMID- 27383986 TI - Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. AB - Inflammatory caspases (caspases 1, 4, 5 and 11) are activated in response to microbial infection and danger signals. When activated, they cleave mouse and human gasdermin D (GSDMD) after Asp276 and Asp275, respectively, to generate an N terminal cleavage product (GSDMD-NT) that triggers inflammatory death (pyroptosis) and release of inflammatory cytokines such as interleukin-1beta. Cleavage removes the C-terminal fragment (GSDMD-CT), which is thought to fold back on GSDMD-NT to inhibit its activation. However, how GSDMD-NT causes cell death is unknown. Here we show that GSDMD-NT oligomerizes in membranes to form pores that are visible by electron microscopy. GSDMD-NT binds to phosphatidylinositol phosphates and phosphatidylserine (restricted to the cell membrane inner leaflet) and cardiolipin (present in the inner and outer leaflets of bacterial membranes). Mutation of four evolutionarily conserved basic residues blocks GSDMD-NT oligomerization, membrane binding, pore formation and pyroptosis. Because of its lipid-binding preferences, GSDMD-NT kills from within the cell, but does not harm neighbouring mammalian cells when it is released during pyroptosis. GSDMD-NT also kills cell-free bacteria in vitro and may have a direct bactericidal effect within the cytosol of host cells, but the importance of direct bacterial killing in controlling in vivo infection remains to be determined. PMID- 27383987 TI - Genetic dissection of Flaviviridae host factors through genome-scale CRISPR screens. AB - The Flaviviridae are a family of viruses that cause severe human diseases. For example, dengue virus (DENV) is a rapidly emerging pathogen causing an estimated 100 million symptomatic infections annually worldwide. No approved antivirals are available to date and clinical trials with a tetravalent dengue vaccine showed disappointingly low protection rates. Hepatitis C virus (HCV) also remains a major medical problem, with 160 million chronically infected patients worldwide and only expensive treatments available. Despite distinct differences in their pathogenesis and modes of transmission, the two viruses share common replication strategies. A detailed understanding of the host functions that determine viral infection is lacking. Here we use a pooled CRISPR genetic screening strategy to comprehensively dissect host factors required for these two highly important Flaviviridae members. For DENV, we identified endoplasmic-reticulum (ER) associated multi-protein complexes involved in signal sequence recognition, N linked glycosylation and ER-associated degradation. DENV replication was nearly completely abrogated in cells deficient in the oligosaccharyltransferase (OST) complex. Mechanistic studies pinpointed viral RNA replication and not entry or translation as the crucial step requiring the OST complex. Moreover, we show that viral non-structural proteins bind to the OST complex. The identified ER associated protein complexes were also important for infection by other mosquito borne flaviviruses including Zika virus, an emerging pathogen causing severe birth defects. By contrast, the most significant genes identified in the HCV screen were distinct and included viral receptors, RNA-binding proteins and enzymes involved in metabolism. We found an unexpected link between intracellular flavin adenine dinucleotide (FAD) levels and HCV replication. This study shows notable divergence in host-depenency factors between DENV and HCV, and illuminates new host targets for antiviral therapy. PMID- 27383985 TI - The quiescent intracluster medium in the core of the Perseus cluster. AB - Clusters of galaxies are the most massive gravitationally bound objects in the Universe and are still forming. They are thus important probes of cosmological parameters and many astrophysical processes. However, knowledge of the dynamics of the pervasive hot gas, the mass of which is much larger than the combined mass of all the stars in the cluster, is lacking. Such knowledge would enable insights into the injection of mechanical energy by the central supermassive black hole and the use of hydrostatic equilibrium for determining cluster masses. X-rays from the core of the Perseus cluster are emitted by the 50-million-kelvin diffuse hot plasma filling its gravitational potential well. The active galactic nucleus of the central galaxy NGC 1275 is pumping jetted energy into the surrounding intracluster medium, creating buoyant bubbles filled with relativistic plasma. These bubbles probably induce motions in the intracluster medium and heat the inner gas, preventing runaway radiative cooling--a process known as active galactic nucleus feedback. Here we report X-ray observations of the core of the Perseus cluster, which reveal a remarkably quiescent atmosphere in which the gas has a line-of-sight velocity dispersion of 164 +/- 10 kilometres per second in the region 30-60 kiloparsecs from the central nucleus. A gradient in the line-of sight velocity of 150 +/- 70 kilometres per second is found across the 60 kiloparsec image of the cluster core. Turbulent pressure support in the gas is four per cent of the thermodynamic pressure, with large-scale shear at most doubling this estimate. We infer that a total cluster mass determined from hydrostatic equilibrium in a central region would require little correction for turbulent pressure. PMID- 27383989 TI - The visualizations transforming biology. PMID- 27383988 TI - A CRISPR screen defines a signal peptide processing pathway required by flaviviruses. AB - Flaviviruses infect hundreds of millions of people annually, and no antiviral therapy is available. We performed a genome-wide CRISPR/Cas9-based screen to identify host genes that, when edited, resulted in reduced flavivirus infection. Here, we validated nine human genes required for flavivirus infectivity, and these were associated with endoplasmic reticulum functions including translocation, protein degradation, and N-linked glycosylation. In particular, a subset of endoplasmic reticulum-associated signal peptidase complex (SPCS) proteins was necessary for proper cleavage of the flavivirus structural proteins (prM and E) and secretion of viral particles. Loss of SPCS1 expression resulted in markedly reduced yield of all Flaviviridae family members tested (West Nile, Dengue, Zika, yellow fever, Japanese encephalitis, and hepatitis C viruses), but had little impact on alphavirus, bunyavirus, or rhabdovirus infection or the surface expression or secretion of diverse host proteins. We found that SPCS1 dependence could be bypassed by replacing the native prM protein leader sequences with a class I major histocompatibility complex (MHC) antigen leader sequence. Thus, SPCS1, either directly or indirectly via its interactions with unknown host proteins, preferentially promotes the processing of specific protein cargo, and Flaviviridae have a unique dependence on this signal peptide processing pathway. SPCS1 and other signal processing pathway members could represent pharmacological targets for inhibiting infection by the expanding number of flaviviruses of medical concern. PMID- 27383991 TI - Whole-body direct 4D parametric PET imaging employing nested generalized Patlak expectation-maximization reconstruction. AB - Whole-body (WB) dynamic PET has recently demonstrated its potential in translating the quantitative benefits of parametric imaging to the clinic. Post reconstruction standard Patlak (sPatlak) WB graphical analysis utilizes multi-bed multi-pass PET acquisition to produce quantitative WB images of the tracer influx rate K i as a complimentary metric to the semi-quantitative standardized uptake value (SUV). The resulting K i images may suffer from high noise due to the need for short acquisition frames. Meanwhile, a generalized Patlak (gPatlak) WB post reconstruction method had been suggested to limit K i bias of sPatlak analysis at regions with non-negligible (18)F-FDG uptake reversibility; however, gPatlak analysis is non-linear and thus can further amplify noise. In the present study, we implemented, within the open-source software for tomographic image reconstruction platform, a clinically adoptable 4D WB reconstruction framework enabling efficient estimation of sPatlak and gPatlak images directly from dynamic multi-bed PET raw data with substantial noise reduction. Furthermore, we employed the optimization transfer methodology to accelerate 4D expectation-maximization (EM) convergence by nesting the fast image-based estimation of Patlak parameters within each iteration cycle of the slower projection-based estimation of dynamic PET images. The novel gPatlak 4D method was initialized from an optimized set of sPatlak ML-EM iterations to facilitate EM convergence. Initially, realistic simulations were conducted utilizing published (18)F-FDG kinetic parameters coupled with the XCAT phantom. Quantitative analyses illustrated enhanced K i target-to-background ratio (TBR) and especially contrast-to-noise ratio (CNR) performance for the 4D versus the indirect methods and static SUV. Furthermore, considerable convergence acceleration was observed for the nested algorithms involving 10-20 sub-iterations. Moreover, systematic reduction in K i % bias and improved TBR were observed for gPatlak versus sPatlak. Finally, validation on clinical WB dynamic data demonstrated the clinical feasibility and superior K i CNR performance for the proposed 4D framework compared to indirect Patlak and SUV imaging. PMID- 27384009 TI - Reply to: Is Etanar a new biologic? M. Scheinberg - Why Etanar is a new biologic type rhTNFR:Fc. PMID- 27384010 TI - Tanner Awards for the Most Cited Articles of 2013. PMID- 27383993 TI - Optimizing Rehabilitation for Phantom Limb Pain Using Mirror Therapy and Transcranial Direct Current Stimulation: A Randomized, Double-Blind Clinical Trial Study Protocol. AB - BACKGROUND: Despite the multiple available pharmacological and behavioral therapies for the management of chronic phantom limb pain (PLP) in lower limb amputees, treatment for this condition is still a major challenge and the results are mixed. Given that PLP is associated with maladaptive brain plasticity, interventions that promote cortical reorganization such as non-invasive brain stimulation and behavioral methods including transcranial direct current stimulation (tDCS) and mirror therapy (MT), respectively, may prove to be beneficial to control pain in PLP. Due to its complementary effects, a combination of tDCS and MT may result in synergistic effects in PLP. OBJECTIVE: The objective of this study is to evaluate the efficacy of tDCS and MT as a rehabilitative tool for the management of PLP in unilateral lower limb amputees. METHODS: A prospective, randomized, placebo-controlled, double-blind, factorial, superiority clinical trial will be carried out. Participants will be eligible if they meet the following inclusion criteria: lower limb unilateral traumatic amputees that present PLP for at least 3 months after the amputated limb has completely healed. Participants (N=132) will be randomly allocated to the following groups: (1) active tDCS and active MT, (2) sham tDCS and active MT, (3) active tDCS and sham MT, and (4) sham tDCS and sham MT. tDCS will be applied with the anodal electrode placed over the primary motor cortex (M1) contralateral to the amputation side and the cathode over the contralateral supraorbital area. Stimulation will be applied at the same time of the MT protocol with the parameters 2 mA for 20 minutes. Pain outcome assessments will be performed at baseline, before and after each intervention session, at the end of MT, and in 2 follow-up visits. In order to assess cortical reorganization and correlate with clinical outcomes, participants will undergo functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) before and after the intervention. RESULTS: This clinical trial received institutional review board (IRB) approval in July of 2015 and enrollment started in December of 2015. To date 2 participants have been enrolled. The estimate enrollment rate is about 30 to 35 patients per year; thus we expect to complete enrollment in 4 years. CONCLUSIONS: This factorial design will provide relevant data to evaluate whether tDCS combined with MT is more effective than each therapy alone, as well as with no intervention (sham/sham) in patients with chronic PLP after unilateral lower limb amputation. In addition, this randomized clinical trial will help to investigate the neurophysiological mechanisms underlying the disease, which could potentially provide relevant findings for further management of this chronic condition and also help to optimize the use of this novel intervention. TRIAL REGISTRATION: Clinicaltrials.gov NCT02487966; https://clinicaltrials.gov/ct2/show/NCT02487966 (Archived by WebCite at http://www.webcitation.org/6i3GrKMyf). PMID- 27384012 TI - Pineapple Waste Extract for Preventing Oxidation in Model Food Systems. AB - Pineapple (Ananas comosus) is consumed in the form of chunks (canned), cubes, fruit salad, and also in juices, concentrates, and jams. In the processes to produce these products, the waste generated represents a high percentage of the total fruit. Some studies have shown that residues of certain fruits, such as pineapple, have the same antioxidant activity as the fruit pulp. So although these residues are discarded, they could be used as an alternative source of polyphenols, as natural antioxidants. This study is focused on the antioxidant activity of wastes obtained in the production of pineapple products and their application. The polyphenols' scavenging activity was determined by the oxygen radical antioxidant capacity assay. The antioxidant potential was determined in emulsions (o/w) and in muffins, where the primary oxidation products (by peroxide value, PV) and the secondary oxidation products (by thiobarbituric acid reactive substances) were analyzed. In addition the muffins were analyzed by means of a triangular sensory test. The PV method showed that pineapple waste extracts caused a reduction in oxidation products of 59% in emulsions and 91% in the muffins. The reduction in TBARs values for emulsions were 27% and for muffins were 51%. The triangular sensory test showed that the samples containing the extract were not distinguished from the control (alpha = 0.05). PMID- 27384013 TI - Effects of the Polysaccharide from the Sporophyll of Brown Alga Undaria Pinnatifida on Serum Lipid Profile and Fat Tissue Accumulation in Rats Fed a High Fat Diet. AB - We investigated the effects of the polysaccharide from the sporophyll of a selected brown alga Undaria pinnatifida on serum lipid profile, fat tissue accumulation, and gastrointestinal transit time in rats fed a high-fat diet. The algal polysaccharide (AP) was prepared by the treatment of multiple cellulase producing fungi Trichoderma reesei and obtained from the sporophyll with a yield of 38.7% (dry basis). The AP was mostly composed of alginate and fucoidan (up to 89%) in a ratio of 3.75:1. The AP was added to the high-fat diet in concentrations of 0.6% and 1.7% and was given to male Sprague-Dawley rats (5-wk old) for 5 wk. The 1.7% AP addition notably reduced body weight gain and fat tissue accumulation, and it improved the serum lipid profile, including triglycerides, total cholesterol, and very low-density lipoprotein-cholesterol. The effects were associated with increased feces weight and shortened gastrointestinal transit time. In addition, the lipid peroxidation of the liver was decreased in both groups. PMID- 27384014 TI - Efficient Inhibition of Hepatitis B Virus Infection by a preS1-binding Peptide. AB - Entry inhibitors are promising novel antivirals against hepatitis B virus (HBV) infection. The existing potential entry inhibitors have targeted the cellular receptor(s). In this study, we aim to develop the first entry inhibitor that inhibits HBV infection via targeting viral particles. The preS1 segment of the large envelope glycoprotein of HBV is essential for virion attachment and infection. Previously, we obtained a preS1-binding short peptide B10 by screening a phage display peptide library using the N-terminal half of preS1 (residues 1 to 60, genotype C). We report here that by means of concatenation of B10, we identified a quadruple concatemer 4B10 that displayed a markedly increased preS1 binding activity. The main binding site of 4B10 in preS1 was mapped to the receptor binding enhancing region. 4B10 blocked HBV attachment to hepatic cells and inhibited HBV infection of primary human and tupaia hepatocytes at low nanomolar concentrations. The 4B10-mediated inhibition of HBV infection is specific as it did not inhibit the infection of vesicular stomatitis virus glycoprotein pseudotyped lentivirus or human immunodeficiency virus type 1. Moreover, 4B10 showed no binding activity to hepatic cells. In conclusion, we have identified 4B10 as a promising candidate for a novel class of HBV entry inhibitors. PMID- 27384015 TI - Using Tuning-Fork Tests in Diagnosing Fractures. AB - REFERENCE/CITATION: Mugunthan K, Doust J, Kurz B, Glasziou P. Is there sufficient evidence for tuning fork tests in diagnosing fractures? A systematic review. BMJ Open. 2014;4(8):e005238. CLINICAL QUESTION: Does evidence support the use of tuning-fork tests in the diagnosis of fractures in clinical practice? DATA SOURCES: The authors performed a comprehensive literature search of AMED, CAB Abstracts, CINAHL, EMBASE, MEDLINE, SPORTDiscus, and Web of Science from each database's start to November 2012. In addition, they manually searched reference lists from the initial search result to identify relevant studies. The following key words were used independently or in combination: auscultation, barford test, exp fractures, fracture, tf test, tuning fork. STUDY SELECTION: Studies were eligible based on the following criteria: (1) primary studies that assessed the diagnostic accuracy of tuning forks; (2) measured against a recognized reference standard such as magnetic resonance imaging, radiography, or bone scan; and (3) the outcome was reported using pain or reduction of sound. Studies included patients of all ages in all clinical settings with no exclusion for language of publication. Studies were not eligible if they were case series, case-control studies, or narrative review papers. DATA EXTRACTION: Potentially eligible studies were independently assessed by 2 researchers. All relevant articles were included and assessed for inclusion criteria and value using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool, and relevant data were extracted. The QUADAS-2 is an updated version of the original QUADAS and focuses on both the risk of bias and applicability of a study through a series of questions. A third researcher was consulted if the 2 initial reviewers did not reach consensus. Data for the primary outcome measure (accuracy of the test) were presented in a 2 * 2 contingency table to show sensitivity and specificity (using the Wilson score method) and positive and negative likelihood ratios with 95% confidence intervals. MAIN RESULTS: A total of 62 citations were initially identified. Six primary studies (329 patients) were included in the review. The 6 studies assessed the accuracy of 2 tuning-fork test methods (pain induction and reduction of sound transmission). The patients ranged in age from 7 to 84 years. The prevalence of fracture in these patients ranged from 10% to 80% using a reference standard such as magnetic resonance imaging, radiography, or bone scan. The sensitivity of the tuning-fork tests was high, ranging from 75% to 92%. The specificity of the tuning-fork tests had a wide range of 18% to 94%. The positive likelihood ratios ranged from 1.1 to 16.5; the negative likelihood ratios ranged from 0.09 to 0.49. CONCLUSIONS: The studies included in this review demonstrated that tuning-fork tests have some value in ruling out fractures. However, strong evidence is lacking to support the use of current tuning-fork tests to rule in a fracture in clinical practice. Similarly, the tuning-fork tests were not statistically accurate in the diagnosis of fractures for widespread clinical use. Despite the lack of strong evidence for diagnosing all fractures, tuning-fork tests may be appropriate in rural and remote settings in which access to the gold standards for diagnosis of fractures is limited. PMID- 27384016 TI - Translational Research for Improving the Care of Familial Hypercholesterolemia: The "Ten Countries Study" and Beyond. AB - Familial hypercholesterolemia (FH) is the most common and serious form of inherited hyperlipidaemia. Dominantly inherited with high penetrance, untreated FH leads to premature death from coronary artery disease due to accelerated atherosclerosis from birth. Despite its importance, there is still a major shortfall in awareness, detection and treatment of FH worldwide. International models of care for FH have recently been published, but their effective implementation requires the garnering of more knowledge about the condition. The "Ten Countries Study" aims to investigate diagnostic, epidemiological and service aspects, as well as physician practices and patient experiences of FH in several countries in the Asia-Pacific Region and the Southern Hemisphere. Five observational studies are being undertaken that will systematically investigate the following aspects of FH: the phenotypic predictors of low-density lipoprotein receptor mutations, the point prevalence in available community populations, current knowledge and clinical practices among primary care physicians, availability and utilisation of services and facilities, and patient perceptions and personal experiences of the condition. The information gathered will inform better clinical practice and will enable the development of country-specific models of care for FH. PMID- 27384017 TI - Metastatic follicular thyroid carcinoma: a case report. AB - OBJECTIVE: A case of oral metastatic follicular thyroid carcinoma is presented. BACKGROUND: Metastatic tumours are more frequent in older individuals and can be the only sign/symptom of an undiagnosed primary malignancy. CASE REPORT: A 69 year-old lady presented with an enlarging mandibular swelling. Incisional biopsy and imaging studies were suggestive of metastatic follicular thyroid carcinoma. CONCLUSION: Metastatic tumours should be considered in the differential diagnosis of mandibular swellings especially in older individuals. PMID- 27384019 TI - Trapping Aluminum Hydroxide Clusters with Trisilanols during Speciation in Aluminum(III)-Water Systems: Reproducible, Large Scale Access to Molecular Aluminate Models. AB - To gain molecular level insights into the properties of certain functions and units of extended oxides/hydroxides, suitable molecular model compounds are needed. As an attractive route to access such compounds the trapping of early intermediates during the hydrolysis of suitable precursor compounds with the aid of stabilizing ligands is conceivable, which was tested for the aluminum(III)/water system. Indeed, trisilanols proved suitable trapping reagents: their presence during the hydrolysis of Al(i) Bu2 H in dependence on the amount of water used allowed for the isolation of tri- and octanuclear aluminum hydroxide cluster complexes [Al3 (MU2 -OH)3 (THF)3 (PhSi(OSiPh2 O)3 )2 ] (1) and [Al8 (MU3 -OH)2 (MU2 -OH)10 (THF)3 (p-anisylSi(OSiPh2 O)3 )4 ] (2). 1 can be regarded as the Al(OH)3 cyclic trimer, where six protons have been replaced by silyl residues. While 2 features a unique [Al8 (MU3 -OH)2 (MU2 -OH)10 ](12+) core. In contrast to most other known aggregates of this type, 1 and 2 can be readily prepared at reasonable scales, dissolve in common solvents, and retain an intact framework even in the presence of excessive amounts of water. This finding paves the way to future research addressing the reactivity of the individual functional groups. PMID- 27384018 TI - MRI-based computational hemodynamics in patients with aortic coarctation using the lattice Boltzmann methods: Clinical validation study. AB - PURPOSE: To introduce a scheme based on a recent technique in computational hemodynamics, known as the lattice Boltzmann methods (LBM), to noninvasively measure pressure gradients in patients with a coarctation of the aorta (CoA). To provide evidence on the accuracy of the proposed scheme, the computed pressure drop values are compared against those obtained using the reference standard method of catheterization. MATERIALS AND METHODS: Pre- and posttreatment LBM based pressure gradients for 12 patients with CoA were simulated for the time point of peak systole using the open source library OpenLB. Four-dimensional (4D) flow-sensitive phase-contrast MRI at 1.5 Tesla was used to acquire flow and to setup the simulation. The vascular geometry was reconstructed using 3D whole heart MRI. Patients underwent pre- and postinterventional pressure catheterization as a reference standard. RESULTS: There is a significant linear correlation between the pretreatment catheter pressure drops and those computed based on the LBM simulation, r=.85, P<.001. The bias was -0.58 +/- 4.1 mmHg and was not significant ( P=0.64) with a 95% confidence interval (CI) of -3.22 to 2.06. For the posttreatment results, the bias was larger and at -2.54 +/- 3.53 mmHg with a 95% CI of -0.17 to -4.91 mmHg. CONCLUSION: The results indicate a reasonable agreement between the simulation results and the catheter measurements. LBM-based computational hemodynamics can be considered as an alternative to more traditional computational fluid dynamics schemes for noninvasive pressure calculations and can assist in diagnosis and therapy planning. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:139-146. PMID- 27384020 TI - Need for an Australian Indigenous disability workforce strategy: review of the literature. AB - PURPOSE: To identify approaches for developing workforce capacity to deliver the National Disability Insurance Scheme (NDIS) to Indigenous people with disability in Australian rural and remote communities. METHOD: A narrative review of peer reviewed and gray literature was undertaken. Searches of electronic databases and websites of key government and non-government organizations were used to supplement the authors' knowledge of literature that (a) focused on Indigenous peoples in Australia or other countries; (b) referred to people with disability; (c) considered rural/remote settings; (d) recommended workforce strategies; and (e) was published in English between 2004 and 2014. Recommended workforce strategies in each publication were summarized in a narrative synthesis. RESULTS: Six peer-reviewed articles and 12 gray publications met inclusion criteria. Three broad categories of workforce strategies were identified: (a) community-based rehabilitation (CBR) and community-centered approaches; (b) cultural training for all workers; and (c) development of an Indigenous disability workforce. CONCLUSION: An Indigenous disability workforce strategy based on community centered principles and incorporating cultural training and Indigenous disability workforce development may help to ensure that Indigenous people with a disability in rural and remote communities benefit from current disability sector reforms. Indigenous workforce development requires strategies to attract and retain Aboriginal workers. Implications for Rehabilitation Indigenous people with disability living in rural and remote areas experience significant access and equity barriers to culturally appropriate supports and services that enable them to live independent, socially inclusive lives. A workforce strategy based on community-centered principles has potential for ensuring that the disability services sector meets the rehabilitation needs of Aboriginal people with disability living in rural and remote areas. Cultural training and development of an Indigenous disability workforce may help to ensure a culturally safe disability services sector and workforce. PMID- 27384022 TI - Na Li and Matthew Stephens on Modeling Linkage Disequilibrium. PMID- 27384021 TI - Alfred Sturtevant and George Beadle Untangle Inversions. PMID- 27384023 TI - Back to the Future: Mutant Hunts Are Still the Way To Go. AB - Innumerable breakthroughs in many fundamental areas of biology have come from unbiased screens and selections for mutations, either across the genome or within a gene. However, long-standing hurdles to key elements of mutant hunts (mutagenesis, phenotypic characterization, and linkage of phenotype to genotype) have limited the organisms in which mutant hunts could be used. These hurdles are now being eliminated by an explosion of new technologies. We believe that a renewed emphasis on unbiased mutant hunts, in both existing model systems and in those where genetics is just now becoming feasible, will lead to new seminal discoveries and surprises. PMID- 27384024 TI - Weaving a Tapestry from Threads Spun by Geneticists: The Series Perspectives on Genetics, 1987-2008. AB - The Perspectives column was initiated in 1987 when Jan Drake, Editor-in-Chief of GENETICS, invited Jim Crow and William Dove to serve as coeditors of "Anecdotal, Historical, and Critical Commentaries." As the series evolved over 21 years, under the guidance of Crow and Dove, the input of stories told by geneticists from many countries created a panorama of 20th-century genetics. Three recurrent themes are visible: how geneticists have created the science (as solitary investigators, in pairs, or in cooperative groups); how geneticists work hard, but find ways to have fun; and how public and private institutions have sustained the science of genetics, particularly in the United States. This article ends by considering how the Perspectives series and other communication formats can carry forward the core science of genetics from the 20th into the 21st century. PMID- 27384025 TI - Complex Traits and Simple Systems: An Interview with Leonid Kruglyak. AB - The Genetics Society of America's Edward Novitski Prize recognizes an extraordinary level of creativity and intellectual ingenuity in the solution of significant problems in genetics research. The 2016 winner, Leonid Kruglyak, has made innovative contributions to the fields of linkage analysis, population genetics, and genomics, while drawing on a combination of mathematical, computational, and experimental approaches. Among other achievements, his work on statistical standards for genome-wide linkage studies has transformed their experimental design, and the linkage analysis program GENEHUNTER has been used to identify hundreds of human disease loci. Kruglyak's group also pioneered expression quantitative trait locus studies, which enabled variation in global gene expression to shed light on the genetics of complex human diseases. In recent years, his laboratory has focused on using genomic technology to establish Saccharomyces cerevisiae and Caenorhabditis elegans as model organisms for studies of complex genetic variation. PMID- 27384028 TI - Corrigendum. PMID- 27384030 TI - Early- and late-onset essential tremor patients represent clinically distinct subgroups. AB - OBJECTIVE: Essential tremor is a very common disease defined by sparse clinical criteria. It is unlikely that essential tremor is an etiologically homogeneous disease. Stratifying broadly defined diseases using clinical characteristics has often aided the etiopathological understanding. Most studies of essential tremor show 2 distinct age at onset peaks: early and late. This study investigates phenotypical differences between early- and late-onset essential tremor patients. METHODS: We studied a sample of 1137 tremor patients. Of these patients, 978 suffered from definite or probable essential tremor. All of the patients underwent the same standardized examination encompassing, among other items, drawing of the Archimedes spiral and assessment of the Fahn-Tolosa-Marin scale. RESULTS: Two subgroups of early-onset (<= 24 years of age, n = 317) and late onset (>= 46 years of age, n = 356) patients were selected based on the visual and mathematical analysis of the age-at-onset distribution. Tremor severity in both groups was comparable. Tremor progression measured as Archimedes spiral score and the Fahn-Tolosa-Marin subscales divided by the disease duration in 10 year bins was significantly faster in late-onset patients when compared with early-onset patients. Early-onset patients more frequently reported a positive family history and alcohol sensitivity of the tremor. CONCLUSIONS: The age-at onset distribution suggests a distinction between early- and late-onset tremor. Early-onset and late-onset essential tremor differ in the progression rates and the frequencies of a positive family history and history of a positive effect of alcohol on tremor. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27384032 TI - A metabolic stress-induced cell cycle checkpoint in stem cells. PMID- 27384031 TI - Clinical use of the co-formulation of insulin degludec and insulin aspart. AB - AIMS: To provide a review of the available data and practical use of insulin degludec with insulin aspart (IDegAsp). Premixed insulins provide basal and prandial glucose control; however, they have an intermediate-acting prandial insulin component and do not provide as effective basal coverage as true long acting insulins, owing to the physicochemical incompatibility of their individual components, coupled with the inflexibility of adjustment. The molecular structure of the co-formulation of IDegAsp, a novel insulin preparation, allows these two molecules to coexist without affecting their individual pharmacodynamic profiles. METHODS: Clinical evidence in phase 2/3 trials of IDegAsp efficacy and safety in type 1 and type 2 diabetes mellitus (T1DM and T2DM) have been assessed and summarised. RESULTS: In people with T2DM, once- and twice-daily dosing provides similar overall glycaemic control (HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naive patients with T2DM, IDegAsp can be started once or twice-daily, based on individual need. People switching from more than once-daily basal or premix insulin therapy can be converted unit-to-unit to once-daily IDegAsp, although this strategy should be assessed by the physician on an individual basis. CONCLUSIONS: IDegAsp offers physicians and people with T2DM a simpler insulin regimen than other available basal-bolus or premix-based insulin regimens, with stable daytime basal coverage, a lower rate of hypoglycaemia and some flexibility in injection timing compared with premix insulins. PMID- 27384027 TI - Learning to Fish with Genetics: A Primer on the Vertebrate Model Danio rerio. AB - In the last 30 years, the zebrafish has become a widely used model organism for research on vertebrate development and disease. Through a powerful combination of genetics and experimental embryology, significant inroads have been made into the regulation of embryonic axis formation, organogenesis, and the development of neural networks. Research with this model has also expanded into other areas, including the genetic regulation of aging, regeneration, and animal behavior. Zebrafish are a popular model because of the ease with which they can be maintained, their small size and low cost, the ability to obtain hundreds of embryos on a daily basis, and the accessibility, translucency, and rapidity of early developmental stages. This primer describes the swift progress of genetic approaches in zebrafish and highlights recent advances that have led to new insights into vertebrate biology. PMID- 27384033 TI - A Novel Frameshift Mutation of SLC26A4 in a Korean Family With Nonsyndromic Hearing Loss and Enlarged Vestibular Aqueduct. AB - OBJECTIVES: We aimed to identify the causative mutation for siblings in a Korean family with nonsyndromic hearing loss (HL) and enlarged vestibular aqueduct (EVA). The siblings were a 19-year-old female with bilateral profound HL and an 11-year-old male with bilateral moderately severe HL. METHODS: We extracted genomic DNA from blood samples of the siblings with HL, their parents, and 100 controls. We performed mutation analysis for SLC26A4 using direct sequencing. RESULTS: The two siblings were compound heterozygotes with the novel mutation p.I713LfsX8 and the previously described mutation p.H723R. Their parents had heterozygous mono-allelic mutations. Father had p.I713LfsX8 mutation as heterozygous, and mother had p.H723R mutation as heterozygous. However, novel mutation p.I713LfsX8 was not detected in 100 unrelated controls. CONCLUSION: Both mutations identified in this study were located in the sulfate transporter and anti-sigma factor antagonist domain, the core region for membrane targeting of SulP/SLC26 anion transporters, which strongly suggests that failure in membrane trafficking by SLC26A4 is a direct cause of HL in this family. Our study could therefore provide a foundation for further investigations elucidating the SLC26A4 related mechanisms of HL. PMID- 27384034 TI - Cause and Management of Patients With Failed Endonasal Dacryocystorhinostomy. AB - OBJECTIVES: Endonasal dacryocystorhinostomy (DCR) is a well-established treatment method in patients with nasolacrimal duct obstruction. However, there are a few reports about the overall management of failed endonasal DCR. We investigated the causes and management strategies of failed endonasal DCR. METHODS: This retrospective review included 61 patients (61 eyes) who had undergone revision surgery by the same surgeon after failed endonasal DCR between January 2008 and December 2012. The appropriate revision method was determined after analysis of the etiology of failure by the fluorescein dye disappearance test, nasal endoscopy, lacrimal irrigation, and probing. The criteria for success of the revision surgery were defined by the passage of fluid without resistance upon lacrimal irrigation and normalization of the tear meniscus height. RESULTS: The mean duration between the primary endonasal DCR and revision surgery was 15.3 months. The average follow-up period after revision surgery was 12.2 months. The most common cause of endoscopic revision surgery was membranous obstruction. Endoscopic revision surgery was performed in 48 patients, while lacrimal silicone tube intubation under endoscopy was performed in 13 patients. The most common indication for lacrimal silicone tube intubation was functional epiphora. The overall success rate of the revision surgery was 89%. CONCLUSION: The most common cause of failed endonasal DCR was membranous obstruction. When patients with failed endonasal DCR presented at the clinic, it is important to identify the cause of the failure. Revision surgery could increase the final success rate of endonasal DCR. PMID- 27384035 TI - Effect of High Glucose on MUC5B expression in Human Airway Epithelial Cells. AB - OBJECTIVES: Excessive production of mucus results in plugging of the airway tract, which can increase morbidity and mortality in affected patients. In patients with diabetes, inflammatory airway disease appears with more frequent relapse and longer duration of symptoms. However, the effects of high glucose (HG) on the secretion of mucin in inflammatory respiratory diseases are not clear. Therefore, this study was conducted in order to investigate the effect and the brief signaling pathway of HG on MUC5B expression in human airway epithelial cells. METHODS: The effect and signaling pathway of HG on MUC5B expression were investigated using reverse transcriptase-polymerase chain reaction (RT-PCR), real time PCR, enzyme immunoassay, and immunoblot analysis with specific inhibitors and small interfering RNA. RESULTS: HG increased MUC5B expression and epidermal growth factor receptor (EGFR) expression, and activated the phosphorylation of EGFR and p38 mitogen-activated protein kinase (MAPK). Pretreatment with EGFR inhibitor significantly attenuated the HG-induced phosphorylation of p38 MAPK, and pretreatments with p38 inhibitor or EGFR inhibitor significantly attenuated HG-induced MUC5B expression. In addition, knockdown of p38 MAPK by p38 MAPK siRNA significantly blocked HG-induced MUC5B expression. CONCLUSION: These findings suggest that HG induces MUC5B expression via the sequential activations of the EGFR/p38 MAPK signaling pathway in human airway epithelial cells. PMID- 27384026 TI - Chromosome Duplication in Saccharomyces cerevisiae. AB - The accurate and complete replication of genomic DNA is essential for all life. In eukaryotic cells, the assembly of the multi-enzyme replisomes that perform replication is divided into stages that occur at distinct phases of the cell cycle. Replicative DNA helicases are loaded around origins of DNA replication exclusively during G1 phase. The loaded helicases are then activated during S phase and associate with the replicative DNA polymerases and other accessory proteins. The function of the resulting replisomes is monitored by checkpoint proteins that protect arrested replisomes and inhibit new initiation when replication is inhibited. The replisome also coordinates nucleosome disassembly, assembly, and the establishment of sister chromatid cohesion. Finally, when two replisomes converge they are disassembled. Studies in Saccharomyces cerevisiae have led the way in our understanding of these processes. Here, we review our increasingly molecular understanding of these events and their regulation. PMID- 27384036 TI - Fragment-Based Analysis of Ligand Dockings Improves Classification of Actives. AB - We describe ADChemCast, a method for using results from virtual screening to create a richer representation of a target binding site, which may be used to improve ranking of compounds and characterize the determinants of ligand-receptor specificity. ADChemCast clusters docked conformations of ligands based on shared pairwise receptor-ligand interactions within chemically similar structural fragments, building a set of attributes characteristic of binders and nonbinders. Machine learning is then used to build rules from the most informational attributes for use in reranking of compounds. In this report, we use ADChemCast to improve the ranking of compounds in 11 diverse proteins from the Database of Useful Decoys-Enhanced (DUD-E) and demonstrate the utility of the method for characterizing relevant binding attributes in HIV reverse transcriptase. PMID- 27384037 TI - Endoscopic sinus surgery improves cognitive dysfunction in patients with chronic rhinosinusitis. AB - BACKGROUND: Patients with chronic rhinosinusitis (CRS) have been found to have cognitive deficit, as identified using the Cognitive Failures Questionnaire (CFQ), but the exact etiology of cognitive decline is unknown. In this study we aimed to determine whether improvement in concomitant inflammation and disease burden in CRS, using endoscopic sinus surgery (ESS), improves cognitive deficit. We also sought to identify comorbid conditions that effect improvement likelihood. METHODS: Study participants (n = 247) with and without nasal polyposis (CRSwNP, CRSsNP) were prospectively enrolled in this multi institutional, observational outcomes study. Pre- and postoperative cognitive dysfunction was evaluated using the CFQ instrument. Quality of life (QOL) and disease burden was also evaluated using the Rhinosinusitis Disability Index (RSDI), the 22-item SinoNasal Outcome Test (SNOT-22), nasal endoscopy, computed tomography, and the 2-item Patient Health Questionnaire (PHQ-2). RESULTS: Average CFQ total scores improved significantly (p = 0.012) after ESS for patients with follow-up (n = 141). Participants with CRSwNP (n = 51) reported significant postoperative improvements in mean CFQ total scores (p = 0.002) and CFQ distractibility and blunders domain scores (p <= 0.006). No significant postoperative improvement for any average CFQ score was found in CRSsNP (p > 0.086). The magnitude of postoperative improvement in CFQ total and domain mean scores was statistically similar between CRSsNP and CRSwNP (p > 0.115). Depressive disorder, identified using PHQ-2 screening, was the only comorbid condition significantly associated with measurable cognitive deficit (p < 0.001). CONCLUSIONS: Patients with CRS have measurable cognitive decline, and ESS may modestly improve cognitive deficit/CFQ scores. Future investigations are needed to further elucidate the underlying mechanisms responsible for cognitive deficit in patients with CRS and significant associations with depression. PMID- 27384038 TI - Carbon nanotubes functionalized by click chemistry as scaffolds for the preparation of electrochemical immunosensors. Application to the determination of TGF-beta 1 cytokine. AB - An electrochemical immunosensor for the determination of the multifunctional Transforming Growth Factor beta1 (TGF-beta1) cytokine has been prepared using multi-walled carbon nanotube (MWCNT)-modified screen-printed carbon electrodes. MWCNTs were functionalized by means of copper(i) catalyzed azide-alkyne cycloaddition ("click" chemistry) as an efficient strategy for the covalent immobilization of immunoreagents without altering their configurations and preserving their biological activity. Alkyne-functionalized IgGs were also prepared and used to assemble IgG-alkyne-azide-MWCNT conjugates used as scaffolds for the immunosensor preparation. After a blocking step with casein, anti-TGF was immobilized and the target cytokine was sandwiched with biotinylated anti-TGF labeled with poly-HRP-labeled streptavidin. The affinity reaction was monitored amperometrically at -0.20 V using the hydroquinone (HQ)/H2O2 system. The calibration plot for TGF-beta1 exhibited a range of linearity (r2 = 0.995) extending between 5 and 200 pg mL-1 which is suitable for the determination of the target cytokine in human serum. A limit of detection of 1.3 pg mL-1 was achieved. The analytical performance of the immunosensor can be advantageously compared with that claimed for ELISA kits. The immunosensor was applied to the analysis of spiked human serum samples at different concentration levels with excellent recoveries. PMID- 27384039 TI - The Global Food System as a Transport Pathway for Hazardous Chemicals: The Missing Link between Emissions and Exposure. AB - BACKGROUND: Food is a major pathway for human exposure to hazardous chemicals. The modern food system is becoming increasingly complex and globalized, but models for food-borne exposure typically assume locally derived diets or use concentrations directly measured in foods without accounting for food origin. Such approaches may not reflect actual chemical intakes because concentrations depend on food origin, and representative analysis is seldom available. Processing, packaging, storage, and transportation also impart different chemicals to food and are not yet adequately addressed. Thus, the link between environmental emissions and realistic human exposure is effectively broken. OBJECTIVES: We discuss the need for a fully integrated treatment of the modern industrialized food system, and we propose strategies for using existing models and relevant supporting data sources to track chemicals during production, processing, packaging, storage, and transport. DISCUSSION: Fate and bioaccumulation models describe how chemicals distribute in the environment and accumulate through local food webs. Human exposure models can use concentrations in food to determine body burdens based on individual or population characteristics. New models now include the impacts of processing and packaging but are far from comprehensive. We propose to close the gap between emissions and exposure by utilizing a wider variety of models and data sources, including global food trade data, processing, and packaging models. CONCLUSIONS: A comprehensive approach that takes into account the complexity of the modern global food system is essential to enable better prediction of human exposure to chemicals in food, sound risk assessments, and more focused risk abatement strategies. Citation: Ng CA, von Goetz N. 2017. The global food system as a transport pathway for hazardous chemicals: the missing link between emissions and exposure. Environ Health Perspect 125:1-7; http://dx.doi.org/10.1289/EHP168. PMID- 27384040 TI - Efficacy of antimicrobial photodynamic therapy as an adjuvant in periodontal treatment in Down syndrome patients. AB - Down syndrome (DS) has characteristics that include mental retardation, a characteristic phenotype, congenital heart defects, immune disorders, and increased risk of periodontal disease (PD). Antimicrobial photodynamic therapy (aPDT) is the combined use of photosensitizers associated with low-level laser (LLL) and oxygen, leading to singlet oxygen formation, which contributes to the antibacterial activity of the phagocytes, killing bacteria. The objective of this study was to evaluate the efficacy of aPDT as an adjuvant to conventional periodontal treatment of PD in DS patients. A double-blinded, controlled, randomized, split-mouth study was conducted. A total of 13 DS subjects who were 18 years or older and who presented at least one tooth in each quadrant of the mouth with probing pocket depth (PPD) equal to or greater than 5 mm were included. The patients were evaluated at three different times: at the baseline, PPD were obtained. After 1 week, conventional scaling and root planing (SRP) was performed, and two randomly selected quadrants also received aPDT. One month after SRP, all the patients were reevaluated. Periodontal conditions were improved among all the participants. The PDT-with-SRP group presented a nonsignificant reduction in PPD (mean = 1.27 mm, median = 1.17 mm) relative to that of the SRP group (mean = 1.00 mm, median = 0.95 mm). Changes over time were compared using the Wilcoxon test. A significant reduction in median PPD was observed in both groups (p = 0.001). Both types of periodontal treatment, with and without PDT, were similarly effective and were associated with good clinical response. PMID- 27384041 TI - Low-level laser therapy (LLLT) does not reduce subcutaneous adipose tissue by local adipocyte injury but rather by modulation of systemic lipid metabolism. AB - Low-level laser (light) therapy (LLLT) has been applied recently to body contouring. However the mechanism of LLLT-induced reduction of subcutaneous adipose tissue thickness has not been elucidated and proposed hypotheses are highly controversial. Non-obese volunteers were subject to 650nm LLLT therapy. Each patient received 6 treatments 2-3 days apart to one side of the abdomen. The contralateral side was left untreated and served as control. Subjects' abdominal adipose tissue thickness was measured by ultrasound imaging at baseline and 2 weeks post-treatment. Our study is to the best of our knowledge, the largest split-abdomen study employing subcutaneous abdominal fat imaging. We could not show a statistically significant reduction of abdominal subcutaneous adipose tissue by LLLT therapy. Paradoxically when the measurements of the loss of fat thickness on treated side was corrected for change in thickness on non treated side, we have observed that in 8 out of 17 patients LLLT increased adipose tissue thickness. In two patients severe side effect occurred as a result of treatment: one patient developed ulceration within appendectomy scar, the other over the posterior superior iliac spine. The paradoxical net increase in subcutaneous fat thickness observed in some of our patients is a rationale against liquefactive and transitory pore models of LLLT-induced adipose tissue reduction. LLLT devices with laser diode panels applied directly on the skin are not as safe as devices with treatment panels separated from the patient's skin. PMID- 27384042 TI - Acute LED irradiation does not change the anaerobic capacity and time to exhaustion during a high-intensity running effort: a double-blind, crossover, and placebo-controlled study : Effects of LED irradiation on anaerobic capacity and performance in running. AB - The purpose of this study was to investigate the acute effects of photobiomodulation therapy using cluster light-emitting diodes (LEDT; 104 diodes) (wavelength 660 and 850 nm; energy density 1.5 and 4.5 J/cm(2); energy 60 J at each point; total energy delivered 600 J) on alternative maximal accumulated oxygen deficit (MAODALT) and time to exhaustion, during a high-intensity running effort. Fifteen moderately active and healthy males (age 25.1 +/- 4.4 years) underwent a graded exercise test and two supramaximal exhaustive efforts at 115 % of the intensity associated with maximal oxygen uptake performed after acute LEDT or placebo irradiation in a double-blind, crossover, and placebo-controlled study design. The MAODALT was assumed as the sum of both oxygen equivalents estimated from the glycolytic and phosphagen metabolism pathways during each supramaximal effort. For the statistical analysis, a paired t test was used to determine differences between the treatments. The significance level was assumed as 95 %. In addition, a qualitative analysis was used to determine the magnitude of differences between groups. No significant differences were found for the values of oxygen equivalents from each energetic metabolism (P >= 0.28), for MAODALT values between the LEDT and placebo conditions (P >= 0.27), or for time to exhaustion (P = 0.80), except for the respiratory exchange ratio (P = 0.01). The magnitude-based inference of effect size reported only a possibly negative effect of photobiomodulation on MAODALT when expressed in units relative to body mass and on the glycolysis pathway (26 %). In summary, LEDT after a high-intensity running effort did not alter the MAODALT, metabolic energy pathways, or high intensity running performance. PMID- 27384043 TI - Obstructive sleep apnea is independently associated with subclinical coronary atherosclerosis among middle-aged women. AB - PURPOSE: Obstructive sleep apnea (OSA) is associated with coronary disease among men. However, this association is not clear for women. In this study, we evaluate the association between OSA and presence of subclinical atherosclerosis assessed by tomographic coronary calcium score in middle-aged women. METHODS: We evaluated consecutive women aged between 45 and 65 years in perimenopause or postmenopause period (with menstrual irregularity-amenorrhea > 60 days), without manifest cardiovascular disease (heart failure, coronary disease, and stroke), from two gynecologic clinics. All patients underwent clinical evaluation, computed tomographic examination for coronary artery calcium (CAC > 100 Agatston units), and portable sleep study. Multiple logistic regression models were used to evaluate the association between OSA and CAC, controlling for traditional risk factors including Framingham Risk Score (FRS), body mass index (BMI), and diabetes. RESULTS: We studied 214 women (age 56 years (52-61); BMI 28 kg/m2 (25 31), 25 % diabetes, 62 % hypertension). OSA (apnea-hypopnea index (AHI) >=5 events/h) was diagnosed in 82 women (38.3 %). CAC was more prevalent in patients with moderate/severe OSA (AHI >=15 events/h) than in patients without or with mild OSA, 19 % vs 4.5 and 1.6 %, respectively (p < 0.01). Moderate to severe OSA was associated with CAC in unadjusted (odds ratio = 6.25, 95 % CI 1.66-23.52; p < 0.01) and adjusted (odds ratio = 8.19, 95 % CI 1.66-40.32; p = 0.01) logistic regression analysis. CONCLUSION: Moderate to severe OSA is independently associated with the presence of CAC in middle-aged women. These results reinforce the concept that women are also susceptible to the cardiovascular consequences of OSA. PMID- 27384044 TI - Drug Toxicity Deaths after Release from Incarceration in Ontario, 2006-2013: Review of Coroner's Cases. AB - BACKGROUND: There is an increased risk of death due to drug toxicity after release from incarceration. The purpose of this study was to describe the timing, rate and circumstances of drug toxicity deaths following release from incarceration. This information can be used to help design potential preventive interventions. METHODS AND FINDINGS: We reviewed coroner's files to identify deaths in adults in Ontario between 2006 and 2013 caused by drug toxicity (n = 6,978) and these records were matched with provincial correctional records to identify individuals who died within one year of being released from incarceration (n = 702). Twenty percent (n = 137) of the 702 deaths occurred within one week of release. The majority (77%, n = 538) of deaths after release involved one or more opioids. Of the deaths involving opioids, intervention by another person may have been possible in 318 cases. CONCLUSIONS: Between 2006 and 2013 in Ontario, one in ten drug toxicity deaths in adults occurred within one year of release from provincial incarceration. These findings may help to inform the implemention and assessment of interventions aimed at reducing drug toxicity deaths following release from incarceration. PMID- 27384046 TI - A Qualitative Approach to Increasing HIV Prevention in Primary Care Settings for Older Adults: Perspectives From Primary Care Providers. AB - The purpose of this research was to explore primary care providers' willingness and ability to increase HIV prevention efforts among older adults and to gain recommendations for improving HIV prevention in primary care settings. Data were collected through 24 semistructured interviews with primary care providers. The results of the study reveal that the majority of providers find it necessary to increase HIV prevention efforts in primary care settings and are willing to do so; however, they cannot do so without assistance. Providers suggested strategies to increase HIV prevention in primary care, for instance, expanding the use of electronic reminders to include HIV prevention and increasing collaboration among providers of different specialties. As a result of the interviews, additional recommendations for increasing HIV prevention have been identified. These findings will aid in improving the quality of care provided to individuals older than 50 in primary care settings. PMID- 27384045 TI - Rottinger approach with dual-mobility cup to improve functional recovery in hip osteoarthritis patients: biomechanical and clinical follow-up. AB - PURPOSE: We assumed that the combination of dual-mobility total hip arthroplasty (THA) using the minimally-invasive Rottinger anterolateral approach could guarantee hip stability with faster functional recovery. We objectively analyzed functional improvement after dual-mobility THA by quantitative gait analysis. METHODS: We compared the results achieved following two different surgical approaches: Rottinger's versus Moore's approach (posterolateral approach). We included 70 patients in an open prospective single-centre study: 38 by Rottinger's approach (age = 67yo) and 32 by Moores's approach (age = 68yo). Clinical and biomechanical analysis (kinematic and kinetic parameters of the hip) were conducted at the pre-operative period and at six months post-op RESULTS: We found a significant improvement in all clinical scores and all biomechanical parameters but no difference was found between the two approaches. However, the study showed marked clinical, biomechanical and functional improvements for patients treated with dual-mobility THA for osteoarthritis without complete hip recovery compared with a control group. CONCLUSIONS: The combination of the Rottinger approach with a dual-mobility cup remains a valid choice for primary THA without functional advantage at midterm. PMID- 27384047 TI - Me & My Wishes: Lessons Learned From Prototyping Resident Centered Videos About Care Preferences. AB - Me & My Wishes are facilitated, resident-centered video-recorded conversations to communicate current and end-of-life care preferences. We describe the video production process of two prototypes in the long-term care (LTC) setting and discuss lessons learned around developing this type of intervention. Partnering with an LTC community allowed us to create videos on-site, document staff time, handle any barriers with video production, and evaluate the process. In this article, we will describe the process of two residents creating Me & My Wishes videos. Both residents responded positively to viewing their edited video (about 20 min), saying the videos would be "good for family or staff to hear feelings about preferences." Staff members also responded positively to the videos. We discuss two key issues to consider: the possibility that resident preferences may change and the resources to produce and view videos. PMID- 27384048 TI - Managing Your Loved One's Health: Development of a New Care Management Measure for Dementia Family Caregivers. AB - The National Alzheimer's Plan calls for improving health care for people living with dementia and supporting their caregivers as capable health care partners. Clinically useful measurement tools are needed to monitor caregivers' knowledge and skills for managing patients' often complex health care needs as well as their own self-care. We created and validated a comprehensive, caregiver-centered measure, Managing Your Loved One's Health (MYLOH), based on a core set of health care management domains endorsed by both providers and caregivers. In this article, we describe its development and preliminary cultural tailoring. MYLOH is a questionnaire containing 29 items, grouped into six domains, which requires <20 min to complete. MYLOH can be used to guide conversations between clinicians and caregivers around health care management of people with dementia, as the basis for targeted health care coaching, and as an outcome measure in comprehensive dementia care management interventions. PMID- 27384049 TI - Wolves Recolonizing Islands: Genetic Consequences and Implications for Conservation and Management. AB - After a long and deliberate persecution, the grey wolf (Canis lupus) is slowly recolonizing its former areas in Europe, and the genetic consequences of this process are of particular interest. Wolves, though present in mainland Estonia for a long time, have only recently started to recolonize the country's two largest islands, Saaremaa and Hiiumaa. The main objective of this study was to analyse wolf population structure and processes in Estonia, with particular attention to the recolonization of islands. Fifteen microsatellite loci were genotyped for 185 individuals across Estonia. As a methodological novelty, all putative wolf-dog hybrids were identified and removed (n = 17) from the dataset beforehand to avoid interference of dog alleles in wolf population analysis. After the preliminary filtering, our final dataset comprised of 168 "pure" wolves. We recommend using hybrid-removal step as a standard precautionary procedure not only for wolf population studies, but also for other taxa prone to hybridization. STRUCTURE indicated four genetic groups in Estonia. Spatially explicit DResD analysis identified two areas, one of them on Saaremaa island and the other in southwestern Estonia, where neighbouring individuals were genetically more similar than expected from an isolation-by-distance null model. Three blending areas and two contrasting transition zones were identified in central Estonia, where the sampled individuals exhibited strong local differentiation over relatively short distance. Wolves on the largest Estonian islands are part of human-wildlife conflict due to livestock depredation. Negative public attitude, especially on Saaremaa where sheep herding is widespread, poses a significant threat for island wolves. To maintain the long term viability of the wolf population on Estonian islands, not only wolf hunting quota should be targeted with extreme care, but effective measures should be applied to avoid inbreeding and minimize conflicts with local communities and stakeholders. PMID- 27384050 TI - Oral Human Papillomavirus Infection in Men Who Have Sex with Men: A Systematic Review and Meta-Analysis. AB - BACKGROUND: The epidemiology of oral human papillomavirus (HPV) infection in men who have sex with men (MSM) differs from anogenital HPV infection. The impact of HPV vaccination has, to date, largely focussed on anogenital outcomes. Vaccination of MSM in the UK has been recommended and, if implemented, baseline estimates of oral HPV prevalence will be useful. METHODS: We searched Medline, Embase and psycINFO databases for studies reporting prevalence, incidence, and clearance of oral HPV infection in MSM. We performed a random-effects meta analysis and meta-regression on prevalence estimates and summarised within-study risk factors for oral HPV DNA detection and incidence/clearance rates. We also performed a meta-analysis of the effect of MSM on oral HPV prevalence compared to heterosexual men. RESULTS: 26 publications were identified. The pooled prevalence of oral HPV16 from twelve estimates was 3.0% (95%CI 0.5-5.5) in HIV-negative and 4.7% (95%CI 2.1-7.3) in HIV-positive MSM. Median age of study participants explained 38% of heterogeneity (p<0.01) in HPV prevalence estimates (pooled = 17% and 29% in HIV-negative and HIV-positive, respectively; 22 estimates). Nine studies compared MSM to heterosexual men and found no difference in oral HPV prevalence (pooled OR 1.07 (95%CI 0.65-1.74)). The clearance rate was higher than incidence within studies. Type-specific concordance between oral and anogenital sites was rare. CONCLUSION: There was substantial heterogeneity between estimates of oral HPV prevalence in MSM populations that was partly explained by HIV status and median age. PMID- 27384051 TI - Universal Versus Targeted Screening for Lynch Syndrome: Comparing Ascertainment and Costs Based on Clinical Experience. AB - BACKGROUND: Strategies to screen colorectal cancers (CRCs) for Lynch syndrome are evolving rapidly; the optimal strategy remains uncertain. AIM: We compared targeted versus universal screening of CRCs for Lynch syndrome. METHODS: In 2010 2011, we employed targeted screening (age < 60 and/or Bethesda criteria). From 2012 to 2014, we screened all CRCs. Immunohistochemistry for the four mismatch repair proteins was done in all cases, followed by other diagnostic studies as indicated. We modeled the diagnostic costs of detecting Lynch syndrome and estimated the 5-year costs of preventing CRC by colonoscopy screening, using a system dynamics model. RESULTS: Using targeted screening, 51/175 (29 %) cancers fit criteria and were tested by immunohistochemistry; 15/51 (29 %, or 8.6 % of all CRCs) showed suspicious loss of >=1 mismatch repair protein. Germline mismatch repair gene mutations were found in 4/4 cases sequenced (11 suspected cases did not have germline testing). Using universal screening, 17/292 (5.8 %) screened cancers had abnormal immunohistochemistry suspicious for Lynch syndrome. Germline mismatch repair mutations were found in only 3/10 cases sequenced (7 suspected cases did not have germline testing). The mean cost to identify Lynch syndrome probands was ~$23,333/case for targeted screening and ~$175,916/case for universal screening at our institution. Estimated costs to identify and screen probands and relatives were: targeted, $9798/case and universal, $38,452/case. CONCLUSIONS: In real-world Lynch syndrome management, incomplete clinical follow up was the major barrier to do genetic testing. Targeted screening costs 2- to 7.5-fold less than universal and rarely misses Lynch syndrome cases. Future changes in testing costs will likely change the optimal algorithm. PMID- 27384053 TI - Established and Emerging Eosinophilic Gastrointestinal Diseases (EGIDs): Seeing Red and Looking Ahead. PMID- 27384052 TI - Structural Change in Microbiota by a Probiotic Cocktail Enhances the Gut Barrier and Reduces Cancer via TLR2 Signaling in a Rat Model of Colon Cancer. AB - BACKGROUND: Structural change in the gut microbiota is implicated in cancer. The beneficial modulation of the microbiota composition with probiotics and prebiotics prevents diseases. AIM: We investigated the effect of oligofructose maltodextrin-enriched Lactobacillus acidophilus, Bifidobacteria bifidum, and Bifidobacteria infantum (LBB), on the gut microbiota composition and progression of colorectal cancer. METHODS: Sprague Dawley rats were acclimatized, given ampicillin (75 mg/kg), and treated as follows; GCO: normal control; GPR: LBB only; GPC: LBB+ 1,2-dimethylhydrazine dihydrochloride (DMH); and GCA: DMH only (cancer control). 16S V4 Pyrosequencing for gut microbiota analysis, tumor studies, and the expression of MUC2, ZO-1, occludin, TLR2, TLR4, caspase 3, COX 2, and beta-catenin were conducted at the end of experiment. RESULTS: Probiotic LBB treatment altered the gut microbiota. The relative abundance of genera Pseudomonas, Congregibacter, Clostridium, Candidactus spp., Phaeobacter, Escherichia, Helicobacter, and HTCC was decreased (P < 0.05), but the genus Lactobacillus increased (P < 0.05), in LBB treatment than in cancer control. The altered gut microbiota was associated with decreased tumor incidence (80 % in GPC vs. 100 % in GCA, P = 0.0001), tumor volume (GPC 84.23 (42.75-188.4) mm(3) vs. GCA 243 (175.5-344.5) mm(3), P < 0.0001) and tumor multiplicity/count (GPC 2.92 +/- 0.26 vs. GCA 6.27 +/- 0.41; P < 0.0001). The expression of MUC2, ZO-1, occludin, and TLR2 was increased, but expression of TLR4, caspase 3, Cox-2, and beta-catenin was decreased by LBB treatment than in cancer control GCA (P < 0.05). CONCLUSION: Administration of LBB modulates the gut microbiota and reduces colon cancer development by decreasing tumor incidence, multiplicity/count, and volume via enhanced TLR2-improved gut mucosa epithelial barrier integrity and suppression of apoptosis and inflammation. PMID- 27384054 TI - Aberrant Force Processing in Schizophrenia. AB - Initially considered as mere side effects of antipsychotic medication, there is now evidence that motor and somatosensory disturbances precede the onset of the illness and can be found in drug-naive patients. However, research on the topic is scarce. Here, we were interested in assessing the accuracy of the neural signal in detecting parametric variations of force linked to a voluntary motor act and a received tactile sensation, either self-generated or externally generated. Patients with a diagnosis of schizophrenia and healthy controls underwent functional magnetic resonance imaging while asked to press, or abstain from pressing, a lever in order to match a visual target force. Forces, exerted and received, varied on 10 levels from 0.5 N to 5 N in 0.5 N increments. Healthy participants revealed a positive correlation between force and activity in contralateral primary somatosensory area (S1) when performing a movement as well as when receiving a tactile sensation but only when this was externally, and not self-, generated. Patients showed evidence of altered force signaling in both motor and tactile conditions, as well as increased correlation with force when tactile sensation was self-generated. Findings are interpreted in line with accounts of predictive and sensory integration mechanisms and point toward alterations in the encoding of parametric forces in the motor and somatosensory domain in patients affected by schizophrenia. PMID- 27384055 TI - A Transdiagnostic Network Approach to Psychosis. AB - Our ability to accurately predict development and outcome of early expression of psychosis is limited. To elucidate the mechanisms underlying psychopathology, a broader, transdiagnostic approach that acknowledges the complexity of mental illness is required. The upcoming network paradigm may be fruitful here. In this study, we applied a transdiagnostic network approach to psychosis. Data pertain to the third wave (second follow-up) of a sample of adolescents originally recruited at age 7-8 years. At baseline, N = 347 children with auditory verbal hallucinations (AVH) and N = 347 control children were included. N = 293 of these N = 694 children participated in the second follow-up (mean age 18.9 years; 59% women). Participants completed the Community Assessment of Psychic Experiences (CAPE) and the Depression, Anxiety and Stress Scale (DASS-21). A specific type of network model, the Ising model, was applied to dichotomized CAPE and DASS items. Interconnections of experiences within the same domain were observed, as well as interconnections between experiences of multiple domains of psychopathology. Quantitative and qualitative differences in network architecture were found in networks of psychopathological experiences in individuals with or without AVH at age 7-8 years. Although adolescents with or without previous AVH did not differ in their current CAPE scores, differences in the interconnectedness of psychopathology items were still found, possibly mirroring a difference in psychosis liability. This study showed that it is possible to map transdiagnostic experiences of psychopathology as a network and that important information can be derived from this approach in comparison to regular approaches. PMID- 27384056 TI - Comparative expression study of sipa family members during early Xenopus laevis development. AB - The signal-induced proliferation-associated (SIPA) protein family belongs to the RapGAP protein superfamily. Previous studies mainly focused on the expression and function of SIPA genes in vertebrate neuronal tissue. Only limited data about the embryonic expression pattern of the genes are currently available. Our study provides the first expression analysis of sipa1, sipa1l1, sipa1l2, and sipa1l3 during early development of the vertebrate organism Xenopus laevis. In silico, analysis revealed that all genes are highly conserved across species. Semi quantitative RT-PCR experiments demonstrated that the RNA of all genes was maternally supplied. By whole mount in situ hybridization approaches, we showed that sipa1 is mainly expressed in various sensory organs, the respiratory and blood system, heart, neural tube, and eye. In contrast, sipa1l1 showed a broad expression during development in particular within the brain, somites, eye, and heart. Sipa1l2 was detected in the branchial arches, glomerulus, and the developing eye. In contrast, sipa1l3 revealed a tissue specific expression within the olfactory and otic vesicles, the cranial placodes and ganglia, neural tube, pronephros, retina, and lens. In summary, all sipa gene family members are expressed throughout the whole developing Xenopus organism and might play an important role during vertebrate early embryogenesis. PMID- 27384058 TI - CT Scan Does Not Differentiate Patients with Hepatopulmonary Syndrome from Other Patients with Liver Disease. AB - BACKGROUND: Hepatopulmonary syndrome (HPS) is defined by liver dysfunction, intrapulmonary vascular dilatations, and impaired oxygenation. The gold standard for detection of intrapulmonary vascular dilatations in HPS is contrast echocardiography. However, two small studies have suggested that patients with HPS have larger segmental pulmonary arterial diameters than both normal subjects and normoxemic subjects with cirrhosis, when measured by CT. We sought to compare CT imaging-based pulmonary vasodilatation in patients with HPS, patients with liver dysfunction without HPS, and matching controls on CT imaging. METHODS: We performed a retrospective cohort study at two quaternary care Canadian HPS centers. We analyzed CT thorax scans in 23 patients with HPS, 29 patients with liver dysfunction without HPS, and 52 gender- and age-matched controls. We measured the artery-bronchus ratios (ABRs) in upper and lower lung zones, calculated the "delta ABR" by subtracting the upper from the lower ABR, compared these measurements between groups, and correlated them with clinically relevant parameters (partial pressure of arterial oxygen, alveolar-arterial oxygen gradient, macroaggregated albumin shunt fraction, and diffusion capacity). We repeated measurements in patients with post-transplant CTs. RESULTS: Patients had significantly larger lower zone ABRs and delta ABRs than controls (1.20 +/- 0.19 versus 0.98 +/- 0.10, p<0.01; and 0.12 +/- 0.17 versus -0.06 +/- 0.10, p<0.01, respectively). However, there were no significant differences between liver disease patients with and without HPS, nor any significant correlations between CT measurements and clinically relevant parameters. There were no significant changes in ABRs after liver transplantation (14 patients). CONCLUSIONS: Basilar segmental artery-bronchus ratios are larger in patients with liver disease than in normal controls, but this vasodilatation is no more severe in patients with HPS. CT does not distinguish patients with HPS from those with uncomplicated liver disease. PMID- 27384057 TI - Caenorhabditis elegans employs innate and learned aversion in response to bacterial toxic metabolites tambjamine and violacein. AB - Bacteriovorus eukaryotes such as nematodes are one of the major natural predators of bacteria. In their defense bacteria have evolved a number of strategies to avoid predation, including the production of deterrent or toxic metabolites, however little is known regarding the response of predators towards such bacterial defenses. Here we use the nematode C. elegans as a model to study a predators' behavioral response towards two toxic bacterial metabolites, tambjamine YP1 and violacein. We found that C. elegans displays an innate avoidance behavior towards tambjamine YP1, however requires previous exposure to violacein before learning to avoid this metabolite. The learned avoidance of violacein is specific, reversible, is mediated via the nematode olfactory apparatus (aversive olfactory learning) and is reduced in the absence of the neurotransmitter serotonin. These multiple strategies to evade bacterial toxic metabolites represent a valuable behavioral adaptation allowing bacteriovorus predators to distinguish between good and bad food sources, thus contributing to the understanding of microbial predator-prey interactions. PMID- 27384059 TI - Cortical Entropy, Mutual Information and Scale-Free Dynamics in Waking Mice. AB - Some neural circuits operate with simple dynamics characterized by one or a few well-defined spatiotemporal scales (e.g. central pattern generators). In contrast, cortical neuronal networks often exhibit richer activity patterns in which all spatiotemporal scales are represented. Such "scale-free" cortical dynamics manifest as cascades of activity with cascade sizes that are distributed according to a power-law. Theory and in vitro experiments suggest that information transmission among cortical circuits is optimized by scale-free dynamics. In vivo tests of this hypothesis have been limited by experimental techniques with insufficient spatial coverage and resolution, i.e., restricted access to a wide range of scales. We overcame these limitations by using genetically encoded voltage imaging to track neural activity in layer 2/3 pyramidal cells across the cortex in mice. As mice recovered from anesthesia, we observed three changes: (a) cortical information capacity increased, (b) information transmission among cortical regions increased and (c) neural activity became scale-free. Our results demonstrate that both information capacity and information transmission are maximized in the awake state in cortical regions with scale-free network dynamics. PMID- 27384060 TI - Foxp2 Regulates Identities and Projection Patterns of Thalamic Nuclei During Development. AB - The molecular mechanisms underlying the formation of the thalamus during development have been investigated intensively. Although transcription factors distinguishing the thalamic primordium from adjacent brain structures have been uncovered, those involved in patterning inside the thalamus are largely unclear. Here, we show that Foxp2, a member of the forkhead transcription factor family, regulates thalamic patterning during development. We found a graded expression pattern of Foxp2 in the thalamic primordium of the mouse embryo. The expression levels of Foxp2 were high in the posterior region and low in the anterior region of the thalamic primordium. In Foxp2 (R552H) knockin mice, which have a missense loss-of-function mutation in the forkhead domain of Foxp2, thalamic nuclei of the posterior region of the thalamus were shrunken, while those of the intermediate region were expanded. Consistently, Foxp2 (R552H) knockin mice showed changes in thalamocortical projection patterns. Our results uncovered important roles of Foxp2 in thalamic patterning and thalamocortical projections during development. PMID- 27384061 TI - Pyoderma Gangrenosum, Acne and Suppurative Hidradenitis Syndrome Treated with Granulocyte and Monocyte Adsorption Apheresis. PMID- 27384062 TI - Disclosure UK website gives "illusion of transparency," says Goldacre. PMID- 27384063 TI - Inflammatory fibroblasts in cancer. AB - The association between inflammation and cancer has been studied widely. Indeed, the tumor microenvironment is influenced by inflammatory cells and affects tumor progression, tumor growth, and the survival of cancer cells. Also, the tumor microenvironment is essential to invasion and metastasis of cancer. Fibroblasts, immune cells, the extracellular matrix and other various components all constitute the tumor stroma, ordinarily referred to as the 'reactive stroma'. Cancer-associated fibroblasts (CAFs), which are activated fibroblasts and one of the components of the tumor microenvironment, are associated with cancer progression, invasiveness and metastasis, and their functional contributions to these processes are beginning to emerge. CAFs mediate tumor-promoting inflammation through various signaling pathways. Epithelial-mesenchymal transition is a process for producing mesenchymal cells during invasion and metastasis of cancer cells. Fibroblasts have been identified as a key player in this mechanism. In the present review, we summarize the relationships between fibroblasts, inflammatory response, the tumor microenvironment and cancer progression. This review provides useful information for the development of cancer prevention and treatment therapies through controlling the inflammatory responses. PMID- 27384064 TI - Ellagic acid inhibits RANKL-induced osteoclast differentiation by suppressing the p38 MAP kinase pathway. AB - Bone undergoes continuous remodeling by a coupled action between osteoblasts and osteoclasts. During osteoporosis, osteoclast activity is often elevated leading to increased bone destruction. Hence, osteoclasts are deemed as potential therapeutic targets to alleviate bone loss. Ellagic acid (EA) is a polyphenol reported to possess anticancer, antioxidant and anti-inflammatory properties. However, its effects on osteoclast formation and function have not yet been examined. Here, we explored the effects of EA on RANKL-induced osteoclast differentiation in RAW264.7 murine macrophages (in vitro) and human CD14+monocytes (ex vivo). EA dose-dependently attenuated RANKL-induced TRAP+ osteoclast formation in osteoclast progenitors with maximal inhibition seen at 1 uM concentration without cytotoxicity. Moreover, owing to perturbed osteoclastogenesis, EA disrupted actin ring formation and bone resorptive function of osteoclasts. Analysis of the underlying molecular mechanisms revealed that EA suppressed the phosphorylation and activation of the p38 MAP kinase pathway which subsequently impaired the RANKL-induced differentiation of osteoclast progenitors. Taken together, these novel results indicate that EA alleviates osteoclastogenesis by suppressing the p38 signaling pathway downstream of RANKL and exerts inhibitory effects on bone resorption and actin ring formation. PMID- 27384065 TI - Flavonol glycosides from the aerial parts of Gynostemma pentaphyllum and their antioxidant activity. AB - The phytochemical investigation of the aerial parts of Gynostemma pentaphyllum led to the isolation of a new flavonol glycoside, gynopentaphylloside (1), along with seven known compounds (2-8). The structure of the new compound was determined on the basis of 1D, 2D NMR and HRESIMS data as well as acid hydrolysis. The antioxidant activity of the isolates was evaluated by a 1,1 diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. PMID- 27384066 TI - Crimean-Congo haemorrhagic fever: transmission to visitors and healthcare workers. AB - Crimean-Congo haemorrhagic fever is a viral haemorrhagic disease, mostly transmitted by tick bites or through contact with infected animal's blood, and bodily fluids. Nosocomial infections were occasionally reported in healthcare settings. We report nosocomial cluster of Crimean-Congo haemorrhagic fever including the visitor with unknown transmission. PMID- 27384067 TI - ELF5 transcription factor expression during gestation in humans and rats - an immunohistochemical analysis. AB - OBJECTIVE: The purpose of this study was to measure immunohistochemically the expression of ELF5 protein in term human and rat placentas and in human placentas associated with gestational diabetes (GD) and intrauterine growth restriction (IUGR). METHODS: The results were quantitated stereologically using the stereological variable of volume density. A semiquantitative analysis was performed independently by a certified pathologist. RESULTS: Total expression of ELF5 protein was higher in pathological pregnancies than in corresponding control term placentas, with both methods of quantifications showing similar results. In addition, ELF5 expression was also higher in connective tissue and blood vessels in chorionic villi in IUGR placentas (but not in GD placentas) compared to healthy controls. ELF5 is higher in placenta as a whole and in most of its components in both pathologies. The two exceptions are chorionic plates in IUGR and decidua in GD, where its expression is lower than in healthy controls. CONCLUSIONS: We have shown that IUGR and GD are associated with significantly increased levels of ELF5 protein in placentas, which suggests that ELF5 may play an important role in normal placentation. However, these are term placentas and to study ELF5 in premature births would give better insight into human placentation in health and disease. PMID- 27384068 TI - Tyrosine Mutation in AAV9 Capsid Improves Gene Transfer to the Mouse Lung. AB - BACKGROUND/AIMS: Adeno-associated virus (AAV) vectors are being increasingly used as the vector of choice for in vivo gene delivery and gene therapy for many pulmonary diseases. Recently, it was shown that phosphorylation of surface exposed tyrosine residues from AAV capsid targets the viral particles for ubiquitination and proteasome-mediated degradation, and mutations of these tyrosine residues lead to highly efficient vector transduction in vitro and in vivo in different organs. In this study, we evaluated the pulmonary transgene expression efficacy of AAV9 vectors containing point mutations in surface-exposed capsid tyrosine residues. METHODS: Eighteen C57BL/6 mice were randomly assigned into three groups: (1) a control group (CTRL) animals underwent intratracheal (i.t.) instillation of saline, (2) the wild-type AAV9 group (WT-AAV9, 1010 vg), and (3) the tyrosine-mutant Y731F AAV9 group (M-AAV9, 1010 vg), which received (i.t.) self-complementary AAV9 vectors containing the DNA sequence of enhanced green fluorescence protein (eGFP). Four weeks after instillation, lung mechanics, morphometry, tissue cellularity, gene expression, inflammatory cytokines, and growth factor expression were analyzed. RESULTS: No significant differences were observed in lung mechanics and morphometry among the experimental groups. However, the number of polymorphonuclear cells was higher in the WT-AAV9 group than in the CTRL and M-AAV9 groups, suggesting that the administration of tyrosine-mutant AAV9 vectors was better tolerated. Tyrosine-mutant AAV9 vectors significantly improved transgene delivery to the lung (30%) compared with their wild-type counterparts, without eliciting an inflammatory response. CONCLUSION: Our results provide the impetus for further studies to exploit the use of AAV9 vectors as a tool for pulmonary gene therapy. PMID- 27384069 TI - Retraction pattern of delaminated rotator cuff tears: dual-layer rotator cuff repair. AB - BACKGROUND: There has been no report to date regarding retraction patterns of delaminated rotator cuff tears. The purpose of this study was to evaluate the incidence and tearing patterns of delamination and repair integrity after the dual-layer repair of delaminated cuff tears. METHODS/DESIGN: A consecutive series of 64 patients with posterosuperior rotator cuff tears underwent arthroscopic rotator cuff repair from August 2011 to September 2012. Among the patients, 53 who received either dual-layer double-row (DLDR) repair or dual-layer suture bridge (DLSB) repair and 11 who received a single-layer repair were evaluated. The mean follow-up period after surgery was 26.5 months. The retraction direction of the deep and superficial layers was analyzed, and the integrity of the repaired constructs was determined in 37 patients through magnetic resonance imaging at a mean of 12.1 months after surgery. RESULTS: The incidence of delamination was 82.8 %. Posteromedial retraction of the deep and superficial layers was observed in 98.1 and 88.5 % of cases, respectively. The Constant score and UCLA score increased preoperatively to postoperatively, showing no significant differences between the dual-layer repair group and single-layer repair group. Retear was found in two (7.6 %) patients in the dual-layer repair group and three (27.2 %) patients in the single-layer repair group (p = 0.016). CONCLUSIONS: Differential rotator cuff repair strategies are needed to address rotator cuff tears, since recent studies have changed our concept of rotator cuff tears. We have focused on three areas: incidence, retraction patterns, and clinical outcomes. The incidence of delamination was extremely high. Both the superficial layer and deep layer were mainly retracted posteromedially. The retraction of the deep layer and superficial layer may be affected by the infraspinatus. Dual-layer rotator cuff repair based on the retraction pattern of delamination is recommended for improvement of repair integrity and of clinical outcomes. PMID- 27384070 TI - Let's call it "aphasia": Rationales for eliminating the term "dysphasia". AB - Health professionals, researchers, and policy makers often consider the two terms aphasia and dysphasia to be synonymous. The aim of this article is to argue the merits of the exclusive use of the term aphasia and present a strategy for creating change through institutions such as the WHO-ICD. Our contention is that one term avoids confusion, speech-language pathologists prefer aphasia, scholarly publications indicate a preference for the term aphasia, stroke clinical guidelines indicate a preference for the term aphasia, consumer organizations use the title aphasia in their name and on their websites, and languages other than English use a term similar to aphasia. The use of the term dysphasia in the broader medical community may stem from the two terms being used interchangeably in the ICD10. Aphasia United http://www.shrs.uq.edu.au/aphasiaunited , an international movement for uniting the voice of all stakeholders in aphasia within an international context, will seek to eliminate the use of the term dysphasia. PMID- 27384071 TI - Apixaban Inhibits Cerebral Microembolic Signals Derived from Carotid Arterial Thrombosis in Rabbits. AB - Cerebral microembolic signal (MES) is an independent predictor of stroke risk and prognosis. The objective of this study is to assess the effects of apixaban, as a representative of the novel oral anticoagulant class, on a rabbit model of cerebral MES. A clinical transcranial Doppler ultrasound instrument was used to assess MESs in the middle cerebral artery in a 30% FeCl3-induced carotid arterial thrombosis model in male New Zealand White rabbits. Ascending doses of apixaban were evaluated as monotherapy and in combination with aspirin on both arterial thrombosis and MES. Pharmacokinetic and pharmacodynamic responses were also evaluated. The effective dose for 50% inhibition (ED50) of thrombus formation for monotherapy was 0.04 mg/kg per hour apixaban, i.v. (0.03 MUM plasma exposure) for the integrated blood flow, 0.13 mg/kg per hour apixaban (0.10 MUM plasma exposure) for thrombus weight, and 0.03 mg/kg per hour apixaban (0.02 MUM plasma exposure) for MES. Dual treatment with aspirin (5 mg/kg, PO) and apixaban (0.015 mg/kg per hour, i.v.) resulted in a significant reduction in cerebral MES (P < 0.05) compared with monotherapy with either agent. Pharmacokinetic analysis of apixaban and pharmacodynamic assays using activated partial thromboplastin time (aPTT) and prothrombin time (PT) for apixaban- and arachidonic acid-induced platelet aggregation for aspirin were used to confirm the exposure-response relationships. In summary, our study demonstrates that apixaban in a concentration-dependent manner inhibits both arterial thrombosis and MES, suggesting a potential association between factor Xa (FXa) blockade and the reduction in MES in patients at risk of ischemic stroke. PMID- 27384073 TI - Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia. AB - Development of social cognition, a unique and high-order function, depends on brain maturation from childhood to adulthood in humans. Autism spectrum disorder (ASD) and schizophrenia have similar social cognitive deficits, although age of onset in each disorder is different. Pathogenesis of these disorders is complex and contains several features, including genetic risk factors, environmental risk factors, and sites of abnormalities in the brain. Although several hypotheses have been postulated, they seem to be insufficient to explain how brain alterations associated with symptoms in these disorders develop at distinct developmental stages. Development of ASD appears to be related to cerebellar dysfunction and subsequent thalamic hyperactivation in early childhood. By contrast, schizophrenia seems to be triggered by thalamic hyperactivation in late adolescence, whereas hippocampal aberration has been possibly initiated in childhood. One of the possible culprits is metal homeostasis disturbances that can induce dysfunction of blood-cerebrospinal fluid barrier. Thalamic hyperactivation is thought to be induced by microglia-mediated neuroinflammation and abnormalities of intracerebral environment. Consequently, it is likely that the thalamic hyperactivation triggers dysregulation of the dorsolateral prefrontal cortex for lower brain regions related to social cognition. In this review, we summarize the brain aberration in ASD and schizophrenia and provide a possible mechanism underlying social cognitive deficits in these disorders based on their distinct ages of onset. PMID- 27384072 TI - Intrathecal Intermittent Orexin-A Causes Sympathetic Long-Term Facilitation and Sensitizes the Peripheral Chemoreceptor Response to Hypoxia in Rats. AB - Intermittent hypoxia causes a persistent increase in sympathetic nerve activity (SNA), which progresses to hypertension in conditions such as obstructive sleep apnea. Orexins (A and B) are hypothalamic neurotransmitters with arousal promoting and sympathoexcitatory effects. We investigated whether the sustained elevation of SNA, termed sympathetic long-term facilitation, after acute intermittent hypoxia (AIH) is caused by endogenous orexin acting on spinal sympathetic preganglionic neurons. The role of orexin in the increased SNA response to AIH was investigated in urethane-anesthetized, vagotomized, and artificially ventilated Sprague-Dawley rats (n = 58). A spinally infused subthreshold dose of orexin-A (intermittent; 0.1 nmol * 10) produced long-term enhancement in SNA (41.4% +/- 6.9%) from baseline. This phenomenon was not produced by the same dose of orexin-A administered as a bolus intrathecal infusion (1 nmol; 7.3% +/- 2.3%). The dual orexin receptor blocker, Almorexant, attenuated the effect of sympathetic long-term facilitation generated by intermittent orexin-A (20.7% +/- 4.5% for Almorexant at 30 mg?kg(-1) and 18.5% +/ 1.2% for 75 mg?kg(-1)), but not in AIH. The peripheral chemoreflex sympathoexcitatory response to hypoxia was greatly enhanced by intermittent orexin-A and AIH. In both cases, the sympathetic chemoreflex sensitization was reduced by Almorexant. Taken together, spinally acting orexin-A is mechanistically sufficient to evoke sympathetic long-term facilitation. However, AIH-induced sympathetic long-term facilitation appears to rely on mechanisms that are independent of orexin neurotransmission. Our findings further reveal that the activation of spinal orexin receptors is critical to enhance peripheral chemoreceptor responses to hypoxia after AIH. PMID- 27384074 TI - CS-3150, a Novel Nonsteroidal Mineralocorticoid Receptor Antagonist, Shows Preventive and Therapeutic Effects On Renal Injury in Deoxycorticosterone Acetate/Salt-Induced Hypertensive Rats. AB - The present study was designed to assess both preventive and therapeutic effects of (S)-1-(2-Hydroxyethyl)-4-methyl-N-[4-(methylsulfonyl) phenyl]-5-[2 (trifluoromethyl) phenyl]-1H-pyrrole-3-carboxamide (CS-3150), a novel nonsteroidal mineralocorticoid receptor antagonist, on renal injury in deoxycorticosterone acetate (DOCA)/salt-induced hypertensive rats (DOCA rats). From 7 weeks of age, DOCA was subcutaneously administered once a week for 4 weeks to uninephrectomized rats fed a high-salt diet. In experiment 1, CS-3150 (0.3-3 mg/kg) was orally administered once a day for 4 weeks coincident with DOCA administration. In experiment 2, after establishment of renal injury by 4 weeks of DOCA/salt loading, CS-3150 (3 mg/kg) was orally administered once a day for 4 weeks with or without continuous DOCA administration. In experiment 1, DOCA/salt loading significantly increased systolic blood pressure (SBP), which was prevented by CS-3150 in a dose-dependent manner. Development of renal injury (proteinuria, renal hypertrophy, and histopathological changes in glomeruli and tubule) was also suppressed by CS-3150 with inhibition of mRNA expression of fibrosis, inflammation, and oxidative stress markers. In experiment 2, under continuous DOCA treatment, CS-3150 clearly ameliorated existing renal injury without lowering SBP, indicating that CS-3150 regressed renal injury independent of its antihypertensive action. Moreover, CS-3150 treatment in combination with withdrawal of DOCA showed further therapeutic effect on renal injury accompanied by reduction in SBP. These results demonstrate that CS-3150 not only prevents but also ameliorates hypertension and renal injury in DOCA rats. Therefore, CS-3150 could be a promising agent for the treatment of hypertension and renal disorders, and may have potential to promote regression of renal injury. PMID- 27384075 TI - Efficacy and safety of cTACE versus DEB-TACE in patients with hepatocellular carcinoma: a meta-analysis. AB - OBJECTIVE: Conflicting results of the efficacy and safety of conventional transarterial chemo-embolization (cTACE) vs drug-eluting bead (DEB)-TACE have been reported. This meta-analysis aimed to update and re-evaluate the efficacy and safety of cTACE compared with those of DEB-TACE in patients with hepatocellular carcinoma (HCC). METHODS: Literature search was performed by two investigators independently in PubMed, MEDLINE and EMBASE to screen studies published from January 1990 to March 2015. Studies of parallel group designs comparing cTACE and DEB-TACE for HCC were reviewed. Complete response, partial response, objective response, disease control, overall survival and survival time were collected to evaluate the efficacy of each therapy. RESULTS: DEB-TACE increased the complete response rate [odds ratio (OR) 1.38, 95% confidence interval (CI) 1.01-1.89], overall survival rate (OR 1.41, 95% CI 1.01-1.98) and survival time [weighted mean difference (WMD) 6.65, 95% CI 6.15-7.14) with less common adverse events (OR 0.59, 95% CI 0.41-0.84). However, DEB-TACE had a similar partial response rate (OR 1.00, 95% CI 0.67-1.49), objective response rate (OR 1.21, 95% CI 0.94-1.56), disease control rate (OR 1.14, 95% CI 0.81 1.58) and serious adverse events (OR 0.86, 95% CI 0.50-1.49) compared with cTACE. CONCLUSIONS: DEB-TACE has a higher complete response rate and a higher overall survival rate in patients with HCC than cTACE; however, the results should be interpreted with caution. Furthermore, DEB-TACE is safer and has less common adverse events than cTACE. PMID- 27384077 TI - Human fetal growth restriction: a cardiovascular journey through to adolescence. AB - Intrauterine growth restriction has been noted to adversely impact morbidity and mortality in the neonatal period as well as cardiovascular well-being in adolescence and adulthood. Recent data based on a wide range of ultrasound parameters during fetal and neonatal life has noted early and persistent involvement of the cardiovascular system. Some of these measures are predictive of long-term morbidities. Assessment of vascular mechanics is a new and novel concept in this population, and opens up avenues for diagnosis, monitoring and evaluation of the likely effectiveness of interventions. Prevention of these adverse vascular and cardiac outcomes secondary to fetal growth restriction may be feasible and of clinical relevance. This review focuses on growth restriction in humans with respect to cardiovascular remodeling and dysfunction during fetal life, persistence of functional cardiac impairment during early childhood and adolescence, and possible preventive strategies. PMID- 27384076 TI - Comparative genomic and functional analyses: unearthing the diversity and specificity of nematicidal factors in Pseudomonas putida strain 1A00316. AB - We isolated Pseudomonas putida (P. putida) strain 1A00316 from Antarctica. This bacterium has a high efficiency against Meloidogyne incognita (M. incognita) in vitro and under greenhouse conditions. The complete genome of P. putida 1A00316 was sequenced using PacBio single molecule real-time (SMRT) technology. A comparative genomic analysis of 16 Pseudomonas strains revealed that although P. putida 1A00316 belonged to P. putida, it was phenotypically more similar to nematicidal Pseudomonas fluorescens (P. fluorescens) strains. We characterized the diversity and specificity of nematicidal factors in P. putida 1A00316 with comparative genomics and functional analysis, and found that P. putida 1A00316 has diverse nematicidal factors including protein alkaline metalloproteinase AprA and two secondary metabolites, hydrogen cyanide and cyclo-(l-isoleucyl-l proline). We show for the first time that cyclo-(l-isoleucyl-l-proline) exhibit nematicidal activity in P. putida. Interestingly, our study had not detected common nematicidal factors such as 2,4-diacetylphloroglucinol (2,4-DAPG) and pyrrolnitrin in P. putida 1A00316. The results of the present study reveal the diversity and specificity of nematicidal factors in P. putida strain 1A00316. PMID- 27384078 TI - Metabolomics of the Antipyretic Effects of Bubali Cornu (Water Buffalo Horn) in Rats. AB - Bubali Cornu (water buffalo horn, WBH) has been used for thousands of years in traditional Chinese medicine (TCM) as an effective treatment for heat. In the present study, we have carried out a metabolomics profiling study on plasma and urine samples to explore potential biomarkers and determine how WBH exerts its antipyretic effects in yeast-induced pyrexia at a metabolomic level. Ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS), together with multivariate statistical analysis, was used to detect and identify potential biomarkers associated with pyrexia and with WBH treatment. In total, sixteen endogenous metabolites were identified in plasma samples and twenty-one metabolites were detected in urine samples. The biomarkers identified in this study, using metabolic pathway analysis (MetPA), are involved in glycerophospholipid, arachidonic acid, amino acid, sphingolipid, and purine metabolism, all of which are disturbed in rats with pyrexia. As a result, WBH affect arachidonic acid metabolism and oxidative stress in yeast-induced pyrexia rats chiefly. The present study determines the important substances underlying the antipyretic efficacy of WBH at a metabolic level. It might pave the way for further investigations into the mechanisms of action of other animal horn-derived traditional Chinese medicines (TCMs). PMID- 27384079 TI - Hepatitis C virus resistance to the new direct-acting antivirals. AB - INTRODUCTION: The treatment of hepatitis C virus (HCV) infection has dramatically improved in recent years with the widespread use of interferon-free combination regimens. Despite the high sustained virological response (SVR) rates (over 90%) obtained with direct-acting antivirals (DAAs), drug resistance has emerged as a potential challenge. The high replication rate of HCV and the low fidelity of its RNA polymerase result in a high degree of genetic variability in the HCV population, which ultimately explains the rapid selection of drug resistance associated variants (RAVs). AREAS COVERED: Results from clinical trials and real world experience have both provided important information on the rate and clinical significance of RAVs. They can be present in treatment-naive patients as natural polymorphisms although more frequently they are selected upon treatment failure. In patients engaged in high-risk behaviors, RAVs can be transmitted. EXPERT OPINION: Although DAA failures generally occur in less than 10% of treated chronic hepatitis C patients, selection of drug resistance is the rule in most cases. HCV re-treatment options are available, but first-line therapeutic strategies should be optimized to efficiently prevent DAA failure due to baseline HCV resistance. Considerable progress is being made and next-generation DAAs are coming with pangenotypic activity and higher resistance barrier. PMID- 27384080 TI - Human and canine visceral leishmaniasis in an emerging focus in Aracuai, Minas Gerais: spatial distribution and socio-environmental factors. AB - This study aimed to analyse the spatial distribution of human (2007-2013) and canine (2013) visceral leishmaniasis (VL) in the city of Aracuai, Minas Gerais, Brazil, and identify the socio-environmental factors related to their occurrence. The spatial distribution of human and canine cases was analysed by kernel density estimation (KDE) and the K function. The KDE values were analysed for correlation between human and canine LV and for normalised difference vegetation index (NDVI). Socio-environmental aspects of household structures and surroundings were evaluated. The spatial distribution of human and canine VL cases exhibited a significant aggregated pattern in distances greater than 350 and 75 m, respectively. The higher occurrence of human and canine infection occurred in the central area of the city. A positive correlation between the densities of human and canine cases was observed, as well as a negative correlation between NDVI and densities of human and canine cases. Socio-environmental analysis revealed that the large amount of animals, organic material from trees and deficiencies in environmental sanitation are possibly contributing to the continuation of the transmission cycle of Leishmania infantum in Aracuai. These results can contribute to the planning by competent agencies to reduce the incidence of infection in the city. PMID- 27384081 TI - Calculation of the ELISA's cut-off based on the change-point analysis method for detection of Trypanosoma cruzi infection in Bolivian dogs in the absence of controls. AB - In ELISAs, sera of individuals infected by Trypanosoma cruzi show absorbance values above a cut-off value. The cut-off is generally computed by means of formulas that need absorbance readings of negative (and sometimes positive) controls, which are included in the titer plates amongst the unknown samples. When no controls are available, other techniques should be employed such as change-point analysis. The method was applied to Bolivian dog sera processed by ELISA to diagnose T. cruzi infection. In each titer plate, the change-point analysis estimated a step point which correctly discriminated among known positive and known negative sera, unlike some of the six usual cut-off formulas tested. To analyse the ELISAs results, the change-point method was as good as the usual cut-off formula of the form "mean + 3 standard deviation of negative controls". Change-point analysis is therefore an efficient alternative method to analyse ELISA absorbance values when no controls are available. PMID- 27384082 TI - Study of surface carbohydrates in Galba truncatula tissues before and after infection with Fasciola hepatica. AB - The presence and distribution of surface carbohydrates in the tissues of Galba truncatula snails uninfected or after infection with Fasciola hepatica as well as on the surface of the snail-pathogenic larval stages of the parasite were studied by lectin labelling assay. This is an attempt to find similarities that indicate possible mimicry, utilised by the parasite as an evasion strategy in this snail trematode system. Different binding patterns were identified on head-foot-mantle, hepatopancreas, genital glands, renopericardial complex of the host as well as of the snail-pathogenic larval stages of F. hepatica. The infection with F. hepatica leads to changes of labelling with Glycine max in the head-mantle cells and Arachis hypogaea in the tubular epithelium of the hepatopancreas. The lectin binding on the other snail tissues is not changed by the development of the larvae. Our data clearly demonstrated the similarity in labelling of G. truncatula tissues and the surface of the snail-pathogenic larval stages of F. hepatica. The role of glycosylation of the contact surfaces of both organisms in relation to the host-parasite interactions is also discussed. PMID- 27384083 TI - Larvicidal activity of Syzygium aromaticum (L.) Merr and Citrus sinensis (L.) Osbeck essential oils and their antagonistic effects with temephos in resistant populations of Aedes aegypti. AB - Environmentally friendly botanical larvicides are commonly considered as an alternative to synthetic larvicides against Aedes aegypti Linn. In addition, mosquito resistance to currently used larvicides has motivated research to find new compounds acting via different mechanisms of action, with the goal of controlling the spread of mosquitos. Essential oils have been widely studied for this purpose. This work aims to evaluate the larvicidal potential of Syzygium aromaticum and Citrus sinensis essential oils, either alone or in combination with temephos, on Ae. aegypti populations having different levels of organophosphate resistance. The 50% lethal concentration (LC50) of the essential oils alone and in combination with temephos and the influence of essential oils on vector oviposition were evaluated. The results revealed that essential oils exhibited similar larvicidal activity in resistant populations and susceptible populations. However, S. aromaticum and C. sinensis essential oils in combination with temephos did not decrease resistance profiles. The presence of the evaluated essential oils in oviposition sites significantly decreased the number of eggs compared to sites with tap water. Therefore, the evaluated essential oils are suitable for use in mosquito resistance management, whereas their combinations with temephos are not recommended. Additionally, repellency should be considered during formulation development to avoid mosquito deterrence. PMID- 27384084 TI - How can we deal with the GERD treatment gap? AB - Patients experiencing heartburn and acid regurgitation despite proton pump inhibition therapy who are averse to antireflux surgery fall into what is called the gastroesophageal reflux disease (GERD) treatment gap. This gap may be potentially addressed by several endoscopic and laparoscopic techniques, including gastric bypass surgery for those patients who are obese. These novel techniques do not significantly alter the anatomy of the esophagogastric junction, minimizing short- and long-term adverse effects. This review provides an overview of the assessment of patients with refractory GERD and highlights the strengths and weaknesses of these minimally invasive therapies. PMID- 27384085 TI - Asymmetric Catalytic Synthesis of Thiochromenes via an Acyl Transfer-Initiated Cascade. AB - A novel, reagent-free catalytic transformation of alpha,beta-unsaturated thioesters into 2-substituted thiochromenes has been developed, with carbon dioxide as the only byproduct. Amidine-based catalysts, particularly homobenzotetramisole and its analogues, achieve high enantioselectivities and yields in this process. PMID- 27384086 TI - Self-assembly of PEGylated gold nanoparticles with satellite structures as seeds. AB - We report a very simple method for the self-assembly of spherical gold nanoparticles (AuNPs), coated with poly(ethylene glycol) (PEG), through a slow evaporation process at room temperature. Clusters of particles forming satellite structures may act as seeds for the self-assembly in a crystallization-like process. Based on the transmission electron microscopy (TEM) images obtained a mechanism for the self-assembly was suggested. PMID- 27384087 TI - Complex Fistula-In-Ano: A Small Step Forward in Understanding? PMID- 27384088 TI - A Nomogram to Predict Lymph Node Positivity Following Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer. AB - BACKGROUND: Patients with locally advanced rectal cancer typically receive neoadjuvant chemoradiation followed by total mesorectal excision. Other treatment approaches, including transanal techniques and close surveillance, are becoming increasingly common following positive responses to chemoradiation. Lack of pathologic lymph node staging is one major disadvantage of these novel strategies. OBJECTIVE: The purposes of this study were to determine clinicopathologic factors associated with positive lymph nodes following neoadjuvant chemoradiation for rectal cancer and to create a nomogram using these factors to predict rates of lymph node positivity. DESIGN: This is a retrospective cohort analysis. SETTINGS: This study used the National Cancer Database. PATIENTS: Patients aged 18 to 90 with clinical stage T3/T4, N0, M0 or Tany, N1-2, M0 adenocarcinoma of the rectum who underwent neoadjuvant chemoradiation before total mesorectal excision from 2010 to 2012 were identified. MAIN OUTCOME MEASURES: The primary outcome measure was lymph node positivity after neoadjuvant chemoradiation for locally advanced rectal cancer. Bivariate and multivariate analyses were used to determine the associations of clinicopathologic variables with lymph node positivity. RESULTS: Eight thousand nine hundred eighty-four patients were included. Young age, lower Charlson score, mucinous histology, poorly differentiated and undifferentiated tumors, the presence of lymphovascular invasion, elevated CEA level, and clinical lymph node positivity were significantly predictive of pathologic lymph node positivity following neoadjuvant chemoradiation. The predictive accuracy of the nomogram is 70.9%, with a c index of 0.71. There was minimal deviation between the predicted and observed outcomes. LIMITATIONS: This study is retrospective, and it cannot be determined when in the course of treatment the data were collected. CONCLUSIONS: We created a nomogram to predict lymph node positivity following neoadjuvant chemoradiation for locally advanced rectal cancer that can serve as a valuable complement to imaging to aid clinicians and patients in determining the best treatment strategy. PMID- 27384089 TI - Vascular Anatomy in Laparoscopic Colectomy for Right Colon Cancer. AB - BACKGROUND: The vascular anatomy in the right colon varies; however, related studies are rare, especially on the laparoscopic vascular anatomy of living patients. OBJECTIVE: The purpose of this study was to describe vascular variations around the gastrocolic trunk, middle colic vein, and ileocolic vessels in laparoscopic surgery for right-sided colon cancer. DESIGN: This is a retrospective descriptive study of patients undergoing laparoscopic colectomy for right colon cancer. SETTINGS: The study was conducted at a single tertiary institution in Korea. PATIENTS: Consecutive patients with right colon cancer who underwent laparoscopic right colectomy using the cranial-to-caudal approach (N = 116) between January 2014 and April 2015 were included. MAIN OUTCOME MEASURES: Three colorectal surgeons took photographs and videos of the vascular anatomy during each laparoscopic right colectomy, and these were analyzed for vascular variations. RESULTS: We classified venous variations around the gastrocolic trunk into 2 types (3 subtypes), type 1 (n = 92 (79.3%)), defined as 1 or 2 colic veins draining into the gastrocolic trunk, and type II (n = 24 (20.7%)), defined as having no gastrocolic trunk. We also investigated the tributaries of the superior mesenteric vein. One, 2, and 3 middle colic veins were found in 86 (74.1%), 26 (22.4%), and 4 patients (3.5%). The right colic vein drained directly into the superior mesenteric vein in 22 patients (19.0%). All of the patients had a single ileocolic vein draining into the superior mesenteric vein and a single ileocolic artery from the superior mesenteric artery. The right colic artery from the superior mesenteric artery was present in 38 patients (32.7%). The ileocolic artery passed the superior mesenteric vein anteriorly or posteriorly in 58 patients (50%) each. LIMITATIONS: Unlike cadaver or radiological studies, we could not clarify the complete vessel paths. CONCLUSIONS: We classified vascular anatomic variations in laparoscopic colectomy for right colon cancer, which could be helpful for colorectal surgeons. PMID- 27384090 TI - Does Stenting as a Bridge to Surgery in Left-Sided Colorectal Cancer Obstruction Really Worsen Oncological Outcomes? AB - BACKGROUND: Although self-expandable metal stents are used as a bridge to surgery in patients with colorectal cancer obstruction, their long-term oncological outcomes are unclear. OBJECTIVE: The aim of this study was to investigate long term oncological outcomes of self-expandable metal stents as a bridge to surgery (stent group) compared with direct surgery (direct operation group) in patients with left-sided colorectal cancer obstruction. DESIGN: This was a retrospective chart review. SETTINGS: This study was conducted at a single tertiary academic center. PATIENTS: Of 113 patients who underwent curative surgery for left-sided colorectal cancer obstruction at Asan Medical Center between 2005 and 2011, 42 underwent direct surgery and 71 underwent self-expandable metal stent insertion followed by elective surgery. After 1:1 propensity-score matching, 42 patients were enrolled in both groups, and their postsurgical outcomes were compared. MAIN OUTCOME MEASURES: The primary outcomes of this study were long-term oncological outcomes, including overall survival and recurrence-free survival of patients in both groups. RESULTS: Three- and 5-year overall survival rates were similar in the stent (87.0% and 71.0%) and direct operation (76.4% and 76.4%) groups (p = 0.931). Three- and 5-year recurrence-free survival rates were also similar in the stent (91.9% and 66.4%) and direct operation (81.2% and 71.2%) groups (p = 0.581), as were postsurgical complication rates (9.5% and 16.7%; p = 0.344). No patient in either group experienced a permanent stoma. LIMITATIONS: This study was limited by its small patient numbers and retrospective nature. CONCLUSIONS: The long-term oncological outcomes of self-expandable metal stents as a bridge to surgery may not be inferior to those of direct surgery for left-sided colorectal cancer obstruction. PMID- 27384091 TI - Characteristics of Antibiotic Prophylaxis and Risk of Surgical Site Infections in Open Colectomies. AB - BACKGROUND: Despite numerous trials assessing optimal antibiotic prophylaxis strategies for colorectal surgery, few studies have assessed real-world practice on a national scale with respect to risk of surgical site infections. OBJECTIVE: Using a large national claims database we aimed to describe current use of prophylactic antibiotics (type and duration) and associations with surgical site infection after open colectomies. DESIGN: This was a retrospective study using the Premier Perspective database. SETTINGS: Included were patient hospitalizations nationwide from January 2006 to December 2013. PATIENTS: A total of 90,725 patients who underwent an open colectomy in 445 different hospitals were included in the study. MAIN OUTCOME MEASURES: Multilevel, multivariable logistic regressions measured associations between surgical site infection and type of antibiotic used and duration (day of surgery only, day of surgery and the day after, and >1 day after surgery). RESULTS: Overall surgical site infection prevalence was 5.2% (n = 4750). Most patients (41.8%) received cefoxitin for prophylaxis; other choices were ertapenem (18.2%), cefotetan (10.3%), metronidazole with cefazolin (9.9%), and ampicillin with sulbactam (7.6%), whereas 12.2% received other antibiotics. Distribution of prophylaxis duration was 51.6%, 28.5%, and 19.9% for day of surgery only, day of surgery and the day after, and >1 day after surgery, respectively. Compared with cefoxitin, lower odds for surgical site infection were observed for ampicillin with sulbactam (OR = 0.71 (95% CI, 0.63-0.82)), ertapenem (OR = 0.65 (95% CI, 0.58-0.71)), metronidazole with cefazolin (OR = 0.56 (95% CI, 0.49-0.64)), and "other" (OR = 0.81 (95% CI, 0.73-0.90)); duration was not significantly associated with altered odds for surgical site infection. Sensitivity analyses supported the main findings. LIMITATIONS: The study was limited by its lack of detailed clinical information in the billing data set used. CONCLUSIONS: In this national study assessing real-world use of prophylactic antibiotics in open colectomies, the type of antibiotic used appeared to be associated with up to 44% decreased odds for surgical site infections. Although there are numerous trials on optimal prophylactic strategies, studies that particularly focus on factors that influence the choice of prophylactic antibiotic might provide insights into ways of reducing the burden of surgical site infections in colorectal surgeries. PMID- 27384092 TI - Impact of the Specific Extraction-Site Location on the Risk of Incisional Hernia After Laparoscopic Colorectal Resection. AB - BACKGROUND: The impact of the specific incision used for specimen extraction during laparoscopic colorectal surgery on incisional hernia rates relative to other contributing factors remains unclear. OBJECTIVE: This study aimed to assess the relationship between extraction-site location and incisional hernia after laparoscopic colorectal surgery. DESIGN: This was a retrospective cohort study (January 2000 through December 2011). SETTINGS: The study was conducted at a high volume, specialized colorectal surgery department. PATIENTS: All of the patients undergoing elective laparoscopic colorectal resection were identified from our prospectively maintained institutional database. MAIN OUTCOME MEASURES: Extraction-site and port-site incisional hernias clinically detected by physician or detected on CT scan were collected. Converted cases, defined as the use of a midline incision to perform the operation, were kept in the intent-to-treat analysis. Specific extraction-site groups were compared, and other relevant factors associated with incisional hernia rates were also evaluated with univariate and multivariate analyses. RESULTS: A total of 2148 patients (54.0% with abdominal and 46.0% with pelvic operations) with a mean age of 51.7 +/- 18.2 years (52% women) were reviewed. Used extraction sites were infraumbilical midline (23.7%), stoma site/right or left lower quadrant (15%), periumbilical midline (22.5%), and Pfannenstiel (29.6%) and midline converted (9.2%). Overall crude extraction site incisional hernia rate during a mean follow-up of 5.9 +/- 3.0 years was 7.2% (n = 155). Extraction-site incisional hernia crude rates were highest after periumbilical midline (12.6%) and a midline incision used for conversion to open surgery (12.0%). Independent factors associated with extraction-site incisional hernia were any extraction sites compared with Pfannenstiel (periumbilical midline HR = 12.7; midline converted HR = 13.1; stoma site HR = 28.4; p < 0.001 for each), increased BMI (HR = 1.23; p = 0.002), synchronous port-site hernias (HR = 3.66; p < 0.001), and postoperative superficial surgical-site infection (HR = 2.11; p < 0.001). LIMITATIONS: This study was limited by its retrospective nature, incisional hernia diagnoses based on clinical examination, and heterogeneous surgical population. CONCLUSIONS: Preferential extraction sites to minimize incisional hernia rates should be Pfannenstiel or incisions off the midline. Midline incisions should be avoided when possible. PMID- 27384093 TI - Juvenile Polyps in Denmark From 1995 to 2014. AB - BACKGROUND: Juvenile polyps in the large bowel are rare but the most common type of polyp in children. The prevalence and incidence are unknown, and few studies exist on the occurrence in adults. They are considered not to harbor any malignant potential unless they are part of the hereditary juvenile polyposis syndrome. OBJECTIVE: We aimed to study the demographics of juvenile polyps in Denmark in a 20-year period from 1995 to 2015 in both adults and children. This is the first report on the occurrence, anatomic localization, and reoccurrence of these polyps in a whole population. DESIGN: Data from all of the patients who had been diagnosed with 1 or more juvenile polyp from January 1, 1995, until December 31, 2014, were obtained. SETTINGS: The study was conducted based on patients registered in the nationwide pathological register in Denmark, the Danish Pathology Data Bank. PATIENTS: We detected a total of 1772 patients who had 2108 juvenile polyps removed (male = 946; female = 826). MAIN OUTCOME MEASURES: We noted the sex, age, number, reoccurrence, and localization of polyps. RESULTS: Of the detected juvenile polyps ~75% were detected in adults and ~25% in children. Approximately 96% of the patients had a single juvenile polyp without reoccurrence, 1% fulfilled the diagnostic criteria for juvenile polyposis syndrome (more than 5 polyps), and 5% had multiple juvenile polyps (2-5 polyps). The incidence in the Danish population can be estimated to be between 1:45,000 and 1:65,000. LIMITATIONS: Miscoding or misclassification in the register cannot be ruled out. We only have data for the 20-year period, limiting the evaluation of reoccurrence, and no data for the endoscopic removal procedures. CONCLUSIONS: We conclude that juvenile polyps are rare, with the majority found in adults, and most often found as a single juvenile polyp. A subgroup of patients have juvenile polyposis syndrome, which requires follow-up. PMID- 27384094 TI - Normal Values and Clinical Use of Bedside Sonographic Assessment of Postoperative Gastric Emptying: A Prospective Cohort Study. AB - BACKGROUND: GI dysfunction is common after abdominal surgery. However, assessment and diagnosis currently lack objective measurement. OBJECTIVE: The purpose of this study was to evaluate the feasibility and clinical use of bedside sonographic assessment of gastric emptying by measuring the time to complete emptying of a standard volume of ingested water in patients after colorectal surgery. DESIGN: This was a prospective cohort study. SETTINGS: The study was conducted at a single tertiary institution in Sydney. PATIENTS: Healthy volunteers (n = 30) were studied to establish a reference range. Gastric emptying was then measured in patients (n = 39) before and after colorectal surgery. INTERVENTION: Assessment of gastric emptying was performed on days 1 to 4 by measuring antral cross-sectional area every 10 minutes after ingestion of 250 mL of water. MAIN OUTCOME MEASURES: The time to complete emptying of water was used as a surrogate measure of gastric emptying. Information concerning postoperative outcomes, GI symptoms, and recovery was also recorded. RESULTS: The median time to complete emptying of water for healthy volunteers was 20 minutes (range, 10-40 minutes). The study protocol was completed in 30 of 39 patients. The time to complete emptying of water on day 2 had the best discriminatory power to identify patients with ileus (sensitivity, 85.71%; specificity, 82.61%). Gastric emptying was normal in 20 of 30 (67%) patients, with only 1 case of ileus (false negative). These patients had less nausea (p = 0.0003), earlier intake of solid diet (p = 0.001), and shorter hospital stay (p = 0.040) compared with patients with abnormal gastric emptying. LIMITATIONS: Ultrasound is operator dependent with a learning curve. CONCLUSIONS: Bedside sonographic assessment of gastric emptying is feasible and reliable. Assessment of antral contents with a single ultrasound 40 minutes after ingestion of water enables classification of patients into those with normal and abnormal gastric emptying. When performed on postoperative day 2, it has good sensitivity/specificity for discriminating patients with ileus. PMID- 27384096 TI - Novel Approach of Treatment of Pilonidal Sinus Disease With Thrombin Gelatin Matrix as a Sealant. AB - BACKGROUND: Sacrococcygeal pilonidal sinus disease is a condition caused by insertion of fallen hair shafts into the skin. Different types of operations have been described for the management of pilonidal sinus, yet none of them have proven to be superior to the others. Recently, sealants like fibrin glue have been successfully used. OBJECTIVE: This study aimed to assess the efficacy of thrombin gelatin matrix as a new sealant for pilonidal sinus treatment. DESIGN: This was a prospective study conducted from March 2013 to March 2015. SETTINGS: The study was conducted in private hospitals in Mansoura City. PATIENTS: The study included 36 male patients (72%) and 14 female patients (28%), with a median age of 22 years. INTERVENTIONS: Fifty patients with pilonidal sinus were admitted and treated with thrombin gelatin matrix injection. MAIN OUTCOME MEASURES: Incidence and time of pilonidal sinus recurrence, postoperative pain and complications, duration of hospital stay, healing status, and time to return to work were recorded. RESULTS: The median duration of symptoms was 13 months, median operative time was 18 minutes, and median hospital stay was 6 hours. All of the procedures were conducted as day-case surgeries. Median follow-up duration was 24 months. Three patients (6%) had a breakdown of the sealant, and the wound was managed with daily dressings. Recurrence at 1 year was observed in 2 patients (4%). A total of 96% of patients were satisfied with the outcome of the procedure, and 92% of patients resumed their daily activities within 3 days. LIMITATIONS: Follow-up for a longer duration is required to ascertain the efficacy of this new technique. The cost of this treatment might be challenging for resource-limited communities. CONCLUSIONS: Management of pilonidal sinus using thrombin gelatin matrix, despite being expensive, is an effective, simple treatment that is easy to perform and associated with low recurrence rate, minimal morbidity, and rapid recovery. PMID- 27384095 TI - Clinical Significance of 2 Deep Posterior Perianal Spaces to Complex Cryptoglandular Fistulas. AB - BACKGROUND: Confusion exists regarding the clinical significance of the deep posterior intersphincteric space and deep postanal space to complex perianal fistulas. OBJECTIVE: The purpose of this study was to assess the clinical significance of the 2 deep posterior perianal spaces and to describe in detail the courses of posterior complex cryptoglandular fistula extensions. DESIGN: This was a retrospective study. MRI-based characteristics of selected perianal fistulas were independently evaluated by examiners who focused on lesions in these 2 spaces and were blinded to each other's findings. SETTINGS: This study was conducted in the colorectal surgery and radiology departments of a large university teaching hospital in China. PATIENTS: Included in the study were patients who underwent pelvic MRI for posterior perianal fistula between October 2012 and December 2014. MAIN OUTCOME MEASURES: The occurrence rates of these 2 deep perianal space lesions in posterior cryptoglandular fistulas were determined. RESULTS: A total of 513 primary posterior cryptoglandular fistulas were identified in 508 patients, including 167 deep posterior intersphincteric space lesions (32.6%) and 23 deep postanal space lesions (4.5%). Of those, 173 fistulas (33.7%) were evaluated as complex. The former and latter spaces were involved in 79.2% (137/173) and 13.3% (23/173) of posterior complex fistulas. Compared with deep postanal space lesions, deep posterior intersphincteric space lesions were more common in cases with high transsphincteric or suprasphincteric fistulas (80.1% vs 15.8%), synchronous multiple transsphincteric fistulas (82.4% vs 20.6%), horseshoe-like fistulas (85.5% vs 14.5%), and supralevator fistulas (93.5% vs 16.1%). Similar incidences were also seen in cases with ischioanal involved horseshoe-like fistulas (75.0% vs 25.0%). LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: The deep posterior intersphincteric space is more likely than the deep postanal space to be involved in complex cryptoglandular fistulas and is likely to play a more important role in the management of complex cryptoglandular fistulas. PMID- 27384097 TI - Neighborhood Variation in the Utilization of Laparoscopy for the Treatment of Colon Cancer. AB - BACKGROUND: The rates of laparoscopic colectomy for colon cancer have steadily increased since its inception. Laparoscopic colectomy currently accounts for a third of colectomy procedures in the United States, but little is known regarding the spatial pattern of the utilization of laparoscopy for colon cancer. OBJECTIVE: This study evaluated the utilization of laparoscopy for colon cancer at the neighborhood level in Ontario. DESIGN: Retrospective analysis of prospectively collected data was performed. SETTING: This study was conducted at all hospitals in the province of Ontario. PATIENTS: This population-based study included all patients aged >=18 who received an elective colectomy for colon cancer from April 2008 until March 2012 in the province of Ontario. MAIN OUTCOME MEASURES: The primary outcome measure was the neighborhood rates of laparoscopy. RESULTS: Overall, 9,969 patients underwent surgery, and the cluster analysis identified 74 cold-spot neighborhoods, representing 1.8 million people, or 14% of the population. In the multivariate analysis, patients from rural neighborhoods were less than half as likely to receive laparoscopy, OR 0.44 (95% CI, 0.24-0.84; p = 0.012). Additionally, having a minimally invasive surgery fellowship training facility within the same administrative health region as the neighborhood made it more than 23 times as likely to be a hot spot, OR 25.88 (95% CI, 12.15-55.11; p < 0.001). Neighborhood socioeconomic status was not associated with variation in the utilization of laparoscopy. LIMITATIONS: Patient case mix could affect laparoscopy use. CONCLUSION AND RELEVANCE: This study identified an unequal utilization of laparoscopy for colon cancer within Ontario with rural neighborhoods experiencing low rates of laparoscopic colectomy, whereas neighborhoods in the same administrative region as minimally invasive surgery training centers experienced increased utilization. Further study into the causes of this variation in resource allocation is needed to identify ways to improve more efficient spread of knowledge and technical skills advancement. PMID- 27384098 TI - Diagnostic Accuracy of MRI for Assessment of T Category and Circumferential Resection Margin Involvement in Patients With Rectal Cancer: A Meta-Analysis. AB - BACKGROUND: The prognosis of rectal cancer is directly related to the stage of the tumor at diagnosis. Accurate preoperative staging is essential for selecting patients to receive optimal treatment. OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance of MRI in tumor staging and circumferential resection margin involvement in rectal cancer. DATA SOURCES: A systematic literature search was performed in MEDLINE, EMBASE, PubMed, Cochrane Database of Systematic Reviews, and Web of Science database. STUDY SELECTION: Original articles from 2000 to 2016 on the diagnostic performance of MRI in the staging of rectal cancer and/or assessment of mesorectal fascia status were eligible. MAIN OUTCOME MEASURES: Pooled diagnostic statistics including sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were calculated for invasion of muscularis propria, perirectal tissue, and adjacent organs and for circumferential resection margin involvement through bivariate random-effects modeling. Summary receiver operating characteristic curves were fitted, and areas under summary receiver operating characteristic curves were counted to evaluate the diagnostic performance of MRI for each outcome. RESULTS: Thirty-five studies were eligible for this meta-analysis. Preoperative MRI revealed the highest sensitivity of 0.97 (95% CI, 0.96-0.98) and specificity of 0.97 (95% CI, 0.96-0.98) for muscularis propria invasion and adjacent organ invasion. Areas under summary receiver operating characteristic curves indicated good diagnostic accuracy for each outcome, with the highest of 0.9515 for the assessment of adjacent organ invasion. Significant heterogeneity existed among studies. There was no notable publication bias for each outcome. LIMITATIONS: This meta-analysis revealed relatively high diagnostic accuracy for preoperative MRI, although significant heterogeneity existed. Therefore, exploration should be focused on standardized interpretation criteria and optimal MRI protocols for future studies. CONCLUSIONS: MRI showed relatively high diagnostic accuracy for preoperative T staging and circumferential resection margin assessment and should be reliable for clinical decision making. PMID- 27384099 TI - The Dynamic Transperineal Ultrasound Era of the Evaluation of Obstructed Defecation Syndrome. PMID- 27384100 TI - The Fatal Flaw of Outcome Studies Comparing Colorectal Operations With and Without Mechanical Bowel Preparation: The Absence of Oral Antibiotics! PMID- 27384101 TI - The Authors Reply. PMID- 27384104 TI - Weeding Through Marijuana's Effects on the Brain. PMID- 27384105 TI - An inverse approach to determining spatially varying arterial compliance using ultrasound imaging. AB - The mechanical properties of arteries are implicated in a wide variety of cardiovascular diseases, many of which are expected to involve a strong spatial variation in properties that can be depicted by diagnostic imaging. A pulse wave inverse problem (PWIP) is presented, which can produce spatially resolved estimates of vessel compliance from ultrasound measurements of the vessel wall displacements. The 1D equations governing pulse wave propagation in a flexible tube are parameterized by the spatially varying properties, discrete cosine transform components of the inlet pressure boundary conditions, viscous loss constant and a resistance outlet boundary condition. Gradient descent optimization is used to fit displacements from the model to the measured data by updating the model parameters. Inversion of simulated data showed that the PWIP can accurately recover the correct compliance distribution and inlet pressure under realistic conditions, even under high simulated measurement noise conditions. Silicone phantoms with known compliance contrast were imaged with a clinical ultrasound system. The PWIP produced spatially and quantitatively accurate maps of the phantom compliance compared to independent static property estimates, and the known locations of stiff inclusions (which were as small as 7 mm). The PWIP is necessary for these phantom experiments as the spatiotemporal resolution, measurement noise and compliance contrast does not allow accurate tracking of the pulse wave velocity using traditional approaches (e.g. 50% upstroke markers). Results from simulations indicate reflections generated from material interfaces may negatively affect wave velocity estimates, whereas these reflections are accounted for in the PWIP and do not cause problems. PMID- 27384106 TI - International Trends in Health Science Librarianship Part 19: The Balkan States (Bulgaria and Croatia). AB - This is the 19th in a series of articles exploring international trends in health science librarianship in the 21st century. The focus of the present issue is the Balkan Region (Bulgaria and Croatia). The next regular feature column will investigate two other Balkan states - Serbia and Slovenia. JM. PMID- 27384107 TI - Is Canada Ready for Nationwide Collaboration on Medical School Admissions Practices and Policies? AB - The report by the Association of Faculties of Medicine of Canada (AFMC) entitled "The Future of Medical Education in Canada: A Collective Vision for MD Education" includes recommendations to enhance admissions processes and increase national collaboration. To achieve these goals, the AFMC conducted a nationwide environmental scan appraising medical schools' readiness for national collaboration and progress toward establishing "made-in-Canada" admissions processes. A critical narrative review of the academic and gray literature was conducted as part of this environmental scan. Four core admissions practice and policy domains were identified: (1) social accountability strategies, (2) standardized admissions testing, (3) interviewing procedures, and (4) application procedures.In this article, the authors summarize and discuss the findings of this narrative review with regard to the four domains. They provide documentation of historical and present-day admissions factors relevant to Canadian medical schools' readiness for nationwide collaboration and a descriptive analysis of the facilitators and barriers to establishing "made-in-Canada" admissions processes.All four domains had facilitators and barriers. One barrier, however, cut across multiple domains-medical schools' pursuit of prestige and its potential to conflict with the goals of the other domains. The authors recommend holding a national forum to debate these issues and to advance the AFMC's goals, a process that will not be straightforward. Yet, national collaboration holds promise for applicants, medical schools, and Canada's diverse population of patients, so efforts toward this end must continue. PMID- 27384108 TI - Planning the Literature Review. PMID- 27384109 TI - Measuring Moral Courage for Interns and Residents: Scale Development and Initial Psychometrics. AB - PURPOSE: To develop a practical and psychometrically sound set of survey items that measures moral courage for physicians in the context of patient care. METHOD: In 2013, the 731 internal medicine and surgical interns and residents from two northeastern U.S. academic medical centers were invited to anonymously complete a survey about moral courage, empathy, and speaking up about patient safety breaches. RESULTS: Of the eligible participants, 352 (48%) responded. Principal components analysis of the moral courage items demonstrated a single, meaningful, nine-item factor labeled the Moral Courage Scale for Physicians (MCSP). All item-total score correlations were significant (P < .001) and ranged from 0.57 to 0.76. The Cronbach alpha for the MCSP was 0.90. Consistent with expectations based on theory, MCSP scores were negatively associated with being an intern versus resident (B = -4.17, P < .001), suggesting discriminant validity. MCSP scores were positively associated with respondents' Jefferson Scale of Physician Empathy perspective-taking score (B = 0.53, P < .001), a construct conceptually relevant to moral courage, suggesting convergent validity. Finally, MCSP scores were positively correlated with self-reported speaking up about patient safety breaches (r = 0.19, P = .008), an action that involves moral courage, suggesting concurrent validity. CONCLUSIONS: The authors provided initial evidence for the reliability and validity of a measure of moral courage for physicians. The MCSP may help researchers and educators to tangibly measure physician moral courage as a concept, and track progress on a set of desired behaviors in response to curricular interventions. PMID- 27384110 TI - Combining in Vitro Folding with Cell Free Protein Synthesis for Membrane Protein Expression. AB - Cell free protein synthesis (CFPS) has emerged as a promising methodology for protein expression. While polypeptide production is very reliable and efficient using CFPS, the correct cotranslational folding of membrane proteins during CFPS is still a challenge. In this contribution, we describe a two-step protocol in which the integral membrane protein is initially expressed by CFPS as a precipitate followed by an in vitro folding procedure using lipid vesicles for converting the protein precipitate to the correctly folded protein. We demonstrate the feasibility of using this approach for the K(+) channels KcsA and MVP and the amino acid transporter LeuT. We determine the crystal structure of the KcsA channel obtained by CFPS and in vitro folding to show the structural similarity to the cellular expressed KcsA channel and to establish the feasibility of using this two-step approach for membrane protein production for structural studies. Our studies show that the correct folding of these membrane proteins with complex topologies can take place in vitro without the involvement of the cellular machinery for membrane protein biogenesis. This indicates that the folding instructions for these complex membrane proteins are contained entirely within the protein sequence. PMID- 27384111 TI - miR-204 Targets PERK and Regulates UPR Signaling and beta-Cell Apoptosis. AB - Endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of diabetes and the associated beta-cell apoptosis. Although microRNAs (miRNAs) have been widely studied in various diseases including diabetes, the role of miRNAs in ER stress and beta-cell apoptosis has only started to be elucidated. We recently showed that diabetes increases beta-cell miR-204 and have now discovered that miR 204 directly targets the 3'untranslated region of protein kinase R-like ER kinase (PERK), 1 of the 3 ER transmembrane sensors and a key factor of the unfolded protein response (UPR). In addition, by using primary human islets, mouse islets, and INS-1 beta-cells, we found that miR-204 decreased PERK expression as well as its downstream factors, activating transcription factor 4 and CCAAT enhancer binding protein homologous protein, whereas it had no effect on the other 2 ER transmembrane sensors, activating transcription factor 6 and inositol-requiring enzyme-1alpha. Interestingly, we discovered that miR-204 also inhibited PERK signaling in the context of ER stress, and this exacerbated ER stress-induced beta-cell apoptosis. This effect could be mimicked by PERK inhibitors supporting the notion that the miR-204-mediated inhibition of PERK and UPR signaling was conferring these detrimental effects on cell survival. Taken together, we have identified PERK as a novel target of miR-204 and show that miR-204 inhibits PERK signaling and increases ER stress-induced cell death, revealing for the first time a link between this miRNA and UPR. PMID- 27384112 TI - Proteome Analysis of the Hemolymph, Mushroom Body, and Antenna Provides Novel Insight into Honeybee Resistance against Varroa Infestation. AB - Varroa destructor has been identified as a major culprit responsible for the losses of millions of honeybee colonies. Varroa sensitive hygiene (VSH) is a suite of behaviors from adult bees to suppress mite reproduction by uncapping and/or removing mite infested pupae from a sealed brood. Despite the efforts to elucidate the molecular underpinnings of VSH, they remain largely unknown. We investigated the proteome of mushroom bodies (MBs) and antennae of adult bees with and without VSH from a stock selected for VSH based on their response to artificially Varroa-infected brood cells by near-infrared camera observation. The pupal hemolymph proteome was also compared between the VSH-line and the line that was not selected for VSH. The identified 8609 proteins in the hemolymph, MBs, and antennae represent the most depth coverage of the honeybee proteome (>55%) to date. In the hemolymph, the VSH-line adapts a unique strategy to boost the social immunity and drive pupal organogenesis by enhancing energy metabolism and protein biosynthesis. In MBs, the up-regulated proteins implicated in neuronal sensitivity suggest their roles to promote the execution of VSH by activation of synaptic vesicles and calcium channel activities. In antennae, the highly expressed proteins associated with sensitivity of olfactory senses and signal transmissions signify their roles by inputting a strong signal to the MBs for initiating VSH. These observations illustrate that the enhanced social immunities and olfactory and neuronal sensitivity play key roles in the combat against Varroa infestation. The identified candidate markers may be useful for accelerating marker-associated selection for VSH to aid in resistance to a parasite responsible for decline in honeybee health. PMID- 27384113 TI - [Sports-Related Head Injuries]. PMID- 27384114 TI - [Acute Subdural Hematoma in Snowboarders:A Multivariate Analysis of 79 Cases]. AB - Snowboarding-related head injuries have become less common as the number of snowboarders has decreased;however, severe head injuries, such as acute subdural hematomas, occur every snowboarding season. We investigated the characteristics of cases of snowboarding-related acute subdural hematoma treated at our hospital. A total of 3,632 patients with snowboarding-related head injuries seen at our hospital between the 1995/96 and 2012/13 snowboarding seasons were enrolled in this study. Seventy-nine(2.2%)patients were diagnosed with acute subdural hematomas using computed tomography. We statistically analyzed the patient questionnaire responses, clinical records, and radiological findings. We compared the findings of the acute subdural hematoma(ASDH)group with those of the non-ASDH group. Among beginners, falling on a slope, incidents involving gentle slopes, and injuries of unknown origin were significantly more common in the ASDH group. On the other hand, among the intermediate snowboarders, incidents involving jumps, jump failure, and collisions with other snowboarders were more common in the non-ASDH group. Secondly, in an analysis involving subjects who had an ASDH, we compared the beginner group with the intermediate/advanced group. Falling on a slope, incidents involving gentle slopes, pure ASDH, diffuse brain swelling, and death were more common in the beginner group, and ASDH combined with contusions or subarachnoid hemorrhaging and incidents involving a jump were more common in the intermediate/advanced group. Finally, we summarized the cases of 10 subjects with an ASDH as well as diffuse brain swelling. Nine of the 10 patients died, 8 were first-timers or beginners, 6 had incidents involving flat or gentle slopes, and 5 had fallen on a slope. Snowboarding is a recreational sport;therefore, snowboarders must take responsibility for their actions. However, snowboarders, especially beginners, could decrease their risk of ASDH if they are informed about ASDH and take precautions to reduce their risk of falling on gentle slopes. Educational activities related to this topic should continue. PMID- 27384115 TI - [Efficiency of Embosphere in the Pre-Operative Embolization of Meningioma:Clinical Experience]. AB - Embosphere(r) was approved in Japan for embolizing intracranial arteries for the reduction of intraoperative bleeding in January 2014. Until August 2015, we performed embolization for four meningiomas using Embosphere(r). We performed an initial evaluation of all the cases, including evaluation of the clinical courses, change in the maximum tumor diameters and volumes, alteration in the appearance on magnetic resonance imaging(MRI), amount of intraoperative bleeding, complications, and histopathological findings. After embolization, the maximum tumor diameters and volumes slightly decreased on MRI, whereas the signal change on diffusion weighted imaging(DWI)or fluid-attenuated inversion recovery(FLAIR)varied in each case. One case demonstrated a partial signal change on DWI one day after the initial procedure, and another case demonstrated a decrease in perifocal edema on FLAIR. Among our patients, least bleeding was recorded at 6 days after the embolization. Histopathological analysis revealed coagulative necrotic lesions in two cases. The von Kossa stain was used to distinguish Embosphere(r) from the psammoma body. One case involved a thromboembolic complication of the retinocentral artery caused by an Embosphere(r) of 100-300 MUm. Our early-stage experience suggests that an Embosphere(r) of 300-500 MUm should be used for safe embolization before resection to avoid thromboembolic complications because an Embosphere(r) of 100-300 MUm can pass through the dangerous anastomosis. Our present strategy was to resect the tumor approximately seven days after the embolization using Embosphere(r). However, further studies and discussion on the size of Embosphere(r), and the interval between pre-operative embolization and surgical removal are needed. PMID- 27384116 TI - [A Novel, Less Invasive Protection Method for Carotid Artery Stenting]. AB - Purpose: We present a novel, less invasive protection method for carotid artery stenting. Case presentation: A 67-year-old man presented with symptomatic severe left carotid artery stenosis. A transfemoral approach was dangerous because of an abdominal aortic aneurysm. A 6Fr Axcelguide Simmonds catheter was inserted into the right brachial artery, and advanced into the left common carotid artery. Next, a 6Fr Optimo 100-cm catheter was coaxially navigated into the left common carotid artery. A PercuSurge GuardWire 300-cm was coaxially navigated into the left external carotid artery. Under flow reversal with the 2 balloons, another PercuSurge GuardWire 300-cm was navigated into the distal left internal carotid artery through the lesion. After both PercuSurge GuardWire balloons were inflated, the 6Fr Optimo was deflated and retrieved using a catheter exchange technique. Then, under distal double-balloon protection, routine stenting was performed. Conclusions: This technique is safer and less invasive than previous methods, especially in cases with difficult femoral access and vulnerable carotid plaque. PMID- 27384117 TI - [Two Cases of Ruptured Cerebral Aneurysm Complicated with Delayed Coil Protrusion after Coil Embolization]. AB - We report two cases of delayed coil protrusion after coil embolization for ruptured cerebral aneurysms. Case 1:An 82-year-old woman with a subarachnoid hemorrhage due to a ruptured small anterior communicating artery aneurysm underwent successful coil embolization. Eighteen days after the procedure, coil protrusion from the aneurysm into the right anterior cerebral artery was observed without any symptoms. Further coil protrusion did not develop after 28 days. Case 2:A 78-year-old woman with a subarachnoid hemorrhage due to a ruptured small left middle cerebral artery aneurysm underwent successful coil embolization. Twenty days after the procedure, coil protrusion from the aneurysm into the left middle cerebral artery was observed, with a transient ischemic attack. Further coil protrusion did not develop. Both patients recovered with antithrombotic treatment. Even though delayed coil protrusion after coil embolization is rare, it should be recognized as a long-term complication of coil embolization for cerebral aneurysms. PMID- 27384118 TI - [A Ruptured Vertebral Artery Dissecting Aneurysm Involving the Anterior Spinal Artery:A Case Report]. AB - A 50-year-old woman presented with a subarachnoid hemorrhage caused by a ruptured vertebral artery dissecting aneurysm(VADA)involving the anterior spinal artery(ASA). The ASA branched at the proximal component of the dissecting aneurysm. The rupture point was presumed to be the distal region of the dissecting aneurysm. We performed coil embolization of the distal part only in order to prevent rebleeding and preserve the ASA. The patient showed no neurological deficits. Six months after the procedure, an angiogram demonstrated occlusion of a distal portion of the right vertebral artery. However, the ASA was still patent. No rebleeding occurred, and the patient has remained neurologically symptom-free for 3 years from the treatment. ASA-involved VADAs are extremely rare. Treatment strategy is difficult because there are no options for bypass surgery and occlusion of the ASA may lead to quadriplegia unless there is collateral flow to the ASA. Although the outcome of the patient was good with partial coil embolization in this case, the treatment strategy should be carefully considered for ASA-involved VADAs. PMID- 27384119 TI - [A Case of Fibromuscular Dysplasia in a Patient with Various Main Trunk Dissections in the Head and Neck over a Short Period]. AB - We report a case of subarachnoid hemorrhage(SAH)from an intracranial vertebral artery(VA)dissection in a patient with fibromuscular dysplasia(FMD)who presented with headache. A 54-year-old woman complained of spontaneous occipital headache. The dilatation of the left VA was detected on magnetic resonance angiography(MRA). She was diagnosed with left VA dissection(headache onset type). After sudden onset of headache on the second day of hospitalization, her consciousness level, as defined by the Japan Coma Scale, was 300. Computed tomography(CT)revealed SAH. Cerebral angiography showed the dilatation of the left intracranial VA and contrast material pooling, which was suspected to be a sign of dissection. We performed VA intravascular ligation by coil embolization. The postoperative course was good but postoperative MRA revealed arterial wall irregularities in both the extra cranial internal carotid artery and the right VA. Cerebral angiography showed the presence of the string-of-beads sign at these arteries. She was diagnosed with FMD. SAH might develop during the follow-up period in patients with VA dissection, even those in whom the initial symptom is headache. In addition, cases of FMD might also be complicated by various lesions of the main trunk of the cerebral artery. PMID- 27384120 TI - [A Case of Cardiac Arrest Caused by Coronary Spasm Related to Induction of General Anesthesia before Carotid Endarterectomy]. AB - Coronary vasospasm(CV)can cause severe arrhythmia and myocardial infarction(MI). Intraoperative CV is not limited to cardiac surgery alone. We report the case of a patient who experienced cardiac arrest after the induction of general anesthesia, but did not demonstrate any abnormalities on preoperative examination. The patient was a 60-year-old man with no history of ischemic heart disease, with NASCET 80% asymptomatic left internal carotid stenosis(ICS). We decided to perform carotid endarterectomy(CEA). Preoperative stress myocardial scintigraphy did not reveal decreased local uptake. General anesthesia was rapidly induced with propofol and remifentanil, and maintained with sevoflurane. Shortly before the start of CEA, systolic blood pressure dropped to 80 mmHg. Electrocardiography indicated decreased ST, followed by an increase, after which complete atrioventricular block occurred. Cardiopulmonary resuscitation was initiated immediately as the patient's pulse was not palpable;heart beat resumed quickly. CEA was canceled. CV was suspected by the test of nitrate administration to coronary artery performed afterwards. A temporary pacemaker was inserted and carotid artery stenting was performed under local anesthesia. Hence, no pacemaker was used intraoperatively and no abnormality was observed on electrocardiography. In the present case, CV in the coronary artery caused complete atrioventricular block, leading to cardiac arrest after inducing general anesthesia. For ICS treatment performed under general anesthesia, care must be taken regarding the possibility of the occurrence of CV. PMID- 27384121 TI - [A Case of Depressed Skull Fracture Involving only the Inner Table]. AB - Depressed skull fracture commonly results from trauma and usually occurs following high-speed impact with a small object. The outer and inner tables of the skull typically break concurrently. We present a case of depressed skull fracture involving only the inner table. The case resulted in a good outcome with only conservative treatment, although the mechanism remained unclear. Fracture models of cadavers have been the main tool for biomechanical investigation, but this classical method cannot accurately measure mechanical factors. We utilized a computer simulation model to assess the human head following skull fracture. This is the first report of an inner table fracture;the fracture mechanism was determined using a simulated computer model. PMID- 27384122 TI - [Update Knowledge for Brain Tumors(8)Primary Central Nervous System Lymphoma]. PMID- 27384125 TI - Multistable Shape-Reconfigurable Architected Materials. AB - Multistable shape-reconfigurable architected materials encompassing living hinges and enabling combinations of high strength, high volumetric change, and complex shape-morphing patterns are introduced. Analytical and numerical investigations, validated by experiments, are performed to characterize the mechanical behavior of the proposed materials. The proposed architected materials can be constructed from virtually any base material, at any length scale and dimensionality. PMID- 27384126 TI - Ligand-Promoted Meta-C-H Arylation of Anilines, Phenols, and Heterocycles. AB - Here we report the development of a versatile 3-acetylamino-2-hydroxypyridine class of ligands that promote meta-C-H arylation of anilines, heterocyclic aromatic amines, phenols, and 2-benzyl heterocycles using norbornene as a transient mediator. More than 120 examples are presented, demonstrating this ligand scaffold enables a wide substrate and coupling partner scope. Meta-C-H arylation with heterocyclic aryl iodides as coupling partners is also realized for the first time using this ligand. The utility for this transformation for drug discovery is showcased by allowing the meta-C-H arylation of a lenalidomide derivative. The first steps toward a silver-free protocol for this reaction are also demonstrated. PMID- 27384127 TI - aMAP is a validated pipeline for registration and segmentation of high-resolution mouse brain data. AB - The validation of automated image registration and segmentation is crucial for accurate and reliable mapping of brain connectivity and function in three dimensional (3D) data sets. While validation standards are necessarily high and routinely met in the clinical arena, they have to date been lacking for high resolution microscopy data sets obtained from the rodent brain. Here we present a tool for optimized automated mouse atlas propagation (aMAP) based on clinical registration software (NiftyReg) for anatomical segmentation of high-resolution 3D fluorescence images of the adult mouse brain. We empirically evaluate aMAP as a method for registration and subsequent segmentation by validating it against the performance of expert human raters. This study therefore establishes a benchmark standard for mapping the molecular function and cellular connectivity of the rodent brain. PMID- 27384128 TI - Photoelectrocatalytic inactivation of fecal coliform bacteria in urban wastewater using nanoparticulated films of TiO2 and TiO2/Ag. AB - Photocatalysis has shown the ability to inactivate a wide range of harmful microorganisms with traditional use of chlorination. Photocatalysis combined with applied bias potential (photoelectrocatalysis) increases the efficiency of photocatalysis and decreases the charge recombination. This work examines the inactivation of fecal coliform bacteria present in real urban wastewater by photoelectrocatalysis using nanoparticulated films of TiO2 and TiO2/Ag (4%w/w) under UV light irradiation. The catalysts were prepared with different thicknesses by the sol-gel method and calcined at 400 degrees C and 600 degrees C. The urban wastewater samples were collected from the sedimentation tank effluent of the university sewage treatment facility. The rate of bacteria inactivation increases with increasing the applied potential and film thicknesses; also, the presence of silver on the catalyst surface annealed at 400 degrees C shows better inactivation than that at 600 degrees C. Finally, a structural cell damage of Escherichia coli (DH5alpha), inoculated in water, is observed during the photoelectrocatalytic process. PMID- 27384129 TI - mCSM-lig: quantifying the effects of mutations on protein-small molecule affinity in genetic disease and emergence of drug resistance. AB - The ability to predict how a mutation affects ligand binding is an essential step in understanding, anticipating and improving the design of new treatments for drug resistance, and in understanding genetic diseases. Here we present mCSM-lig, a structure-guided computational approach for quantifying the effects of single point missense mutations on affinities of small molecules for proteins. mCSM-lig uses graph-based signatures to represent the wild-type environment of mutations, and small-molecule chemical features and changes in protein stability as evidence to train a predictive model using a representative set of protein-ligand complexes from the Platinum database. We show our method provides a very good correlation with experimental data (up to rho = 0.67) and is effective in predicting a range of chemotherapeutic, antiviral and antibiotic resistance mutations, providing useful insights for genotypic screening and to guide drug development. mCSM-lig also provides insights into understanding Mendelian disease mutations and as a tool for guiding protein design. mCSM-lig is freely available as a web server at http://structure.bioc.cam.ac.uk/mcsm_lig. PMID- 27384131 TI - Qualitative analysis of major constituents from Xue Fu Zhu Yu Decoction using ultra high performance liquid chromatography with hybrid ion trap time-of-flight mass spectrometry. AB - Xue Fu Zhu Yu Decoction, a famous formula that has been used for treating many blood stasis-caused diseases for many centuries, comprises 11 kinds of traditional Chinese medicines. A convenient, efficient, and rapid analytical method was developed to simultaneously determine the major compounds in this decoction. An ultra-high performance liquid chromatography with hybrid ion trap time-of-flight mass spectrometry method was used to rapidly separate and detect the major constituents of the decoction. Using this technique, we identified or tentatively identified 34 compounds, including 21 flavonoids, 5 terpenoids, 3 organic acids, 2 lactones, 1 alkaloid, 1 amino acid, and 1 cyanogenic glycoside. The MS analysis of these constituents was described in detail. Findings may contribute to future metabolic and pharmacokinetic studies of this medicine. PMID- 27384132 TI - A Decennary Journey towards the Efficient Asymmetric Hydrogenation of Highly Functionalized Ketones. AB - Around 2006, our group launched a long-term project on the asymmetric hydrogenation of functionalized ketones by using ruthenium complexes with SunPhos ligands. In this review, we recount the burgeoning and blossoming of this project. At the outset, we attempted some benchmark reactions with an array of monofunctionalized ketones, including alpha- and beta-keto esters/amides, beta keto sulfones, phosphonates, and alpha-hydroxy ketones. For alpha-keto esters and amides, we discovered that CeCl3 *7H2 O was an efficient additive for both activity and enantioselectivity. The element iodine was found to be a valid additive for beta-keto sulfones. beta,gamma-Unsaturated alpha-keto acids and esters were also hydrogenated to the saturated chiral blocks with good enantioselectivity and a high turnover number. For the alpha-substituted beta keto esters and phosphonates, exceptionally high stereoselectivity was achieved through dynamic kinetic resolution. Based on these incipient successes, we diverted to bifunctionalized ketone substrates, such as gamma-heteroatom substituted beta-keto esters and delta-ketal-beta-keto esters. For the delta ketal-beta-keto esters, CaCO3 was added to stabilize the delta-ketal groups, which ensured the formation of delta-ketal-beta-hydroxy esters in good yields and high ee values. More interestingly, gamma-halo-gamma,delta-unsaturated-beta-keto esters were hydrogenated to afford highly enantiopure chiral allyl alcohols under mild and neutral conditions. The distance effect of the directing groups was investigated in beta-, gamma-, and delta-keto amides; the last two were hydrogenated with the Ru-SunPhos-diamine system. To implement the pinpoint recognition of two carbonyl groups in similar chemical propinquity, we compared the reaction rates of different beta-keto acid derivatives. THF was found to be a helpful coordinative solvent to control the chemo- and enantioselectivity for more challenging polycarbonyl substrates, such as 3-oxo glutaric acid derivatives, beta,delta-diketo carboxamides, and gamma-heteroatom-substituted beta-diketones. The effects of solvents and heteroatoms in these substrates were also studied. Applications of these hydrogenation reactions were also exemplified by the employment of the products for important pharmaceutical syntheses. PMID- 27384133 TI - Photosalient Effect of a Diarylethene with a Perfluorocyclohexene Ring. AB - Crystals of a diarylethene with a perfluorocyclohexene ring exhibit a remarkable photosalient effect upon UV light irradiation that is attributed to the structural changes that occur when going from open- to closed-ring isomers in the crystalline state, together with the existence of two conformers with different photoconversions compared with those of a perfluorocyclopentene derivative. Our current results give a design principle for molecular structures so as to achieve the photosalient effect for photochromic crystals. PMID- 27384134 TI - Comparative Study of Heparin-Poloxamer Hydrogel Modified bFGF and aFGF for in Vivo Wound Healing Efficiency. AB - Wound therapy remains a clinical challenge. Incorporation of growth factors (GFs) into heparin-functionalized polymer hydrogel is considered as a promising strategy to improve wound healing efficiency. However, different GFs incorporation into the same heparin-based hydrogels often lead to different wound healing effects, and the underlying GF-induced wound healing mechanisms still remain elusive. Herein, we developed a thermos-sensitive heparin-poloxamer (HP) hydrogel to load and deliver different GFs (aFGF and bFGF) for wound healing in vivo. The resulting GFs-based hydrogels with and without HP hydrogels were systematically evaluated and compared for their wound healing efficiency by extensive in vivo tests, including wound closure rate, granulation formation, re epithelization, cell proliferation, collagen, and angiogenesis expressions. While all GFs-based dressings with and without HP hydrogels exhibited better wound healing efficacy than controls, both HP-aFGF and HP-bFGF hydrogels demonstrated their superior healing activity to improve wound closure, granulation formation, re-epithelization, and blood vessel density by up-regulation of PCNA proliferation and collagen synthesis, as compared to GF dressings alone. More importantly, HP-aFGF dressings exhibited the higher healing efficacy than HP-bFGF dressings, indicating that different a/bFGF surface properties lead to different binding and release behaviors in HP hydrogels, both of which will affect different wound healing efficiency. On the basis of experimental observations, the working mechanisms of different healing effects of HP-GFs on full skin removal wound were proposed. This work provides different views of the design and development of an effective hydrogel-based delivery system for GFs toward rapid wound healing. PMID- 27384135 TI - Thromboembolism in patients with congenital afibrinogenaemia. Long-term observational data and systematic review. AB - Frequent arterial and venous thromboembolism in patients with congenital afibrinogenaemia (CA) is neither understood nor is a safe and effective treatment established. It was our objective to report on the clinical observations and laboratory data contributing to the understanding of the frequency, physiopathology, prognosis and treatment of CA. We observed the long-term clinical course and laboratory data in a cohort of four patients with CA and thromboembolic complications, and conducted a systematic review retrieving all available data. Four patients with CA developed recurrent and extensive arterial and venous thromboembolism (TE) from an age of 25-51 years. In two patients, a treatment strategy targeting at maintaining constantly measurable fibrinogen (Fbg) levels (>=0.5 g/l) either by regular Fbg replacement or by orthotopic liver transplantation resulted in long-term remissions. Radiological imaging documented resolved arterial thrombi after 6-12 months. In contrast, recurrent thromboembolic events were observed in two other patients with infrequent Fbg replacement. A systematic review of the literature revealed 48 reports of TE in patients with CA (median age at first event 31 years), and a favourable outcome in most patients with frequent application of Fbg, aimed at constantly measurable trough levels. Present data suggests that patients with CA are at high risk of arterial and venous thromboembolic events, probably caused by thrombin excess owing to lack of thrombin scavenging by Fbg/fibrin. Regular low-dose Fbg replacement might be a safe and effective treatment option in patients with CA and thromboembolic complications. PMID- 27384147 TI - Molecular Applications of a Size-Consistent State-Specific Multireference Perturbation Theory with Relaxed Model-Space Coefficients. AB - We explore in this paper the efficacy of the Rayleigh-Schrodinger (RS) and the Brillouin-Wigner (BW) perturbative counterparts of our recently developed multireference state-specific coupled-cluster formalism (SS-MRCC) with a complete active space (CAS). It is size-extensive and is designed to avoid intruders. The parent SS-MRCC method uses a sum-of-exponentials type of Ansatz for the wave operator. The redundancy inherent in such a choice is resolved by postulating suitable sufficiency conditions which at the same time ensure size-extensivity and size-consistency. The combining coefficients c MU for phiMU's are completely relaxed and are obtained by diagonalizing an effective operator in the model space, one root of which is the target eigenvalue of our interest. By invokation of a suitable partitioning of the Hamiltonian, very convenient perturbative versions of the formalism in both the RS and the BW forms are developed for the second-order energy. The unperturbed Hamiltonian is akin to the Epstein-Nesbet type when at least one of the orbitals is inactive and is the entire active portion of the Hamiltonian when all the orbitals involved are active. Illustrative numerical applications are presented for potential energy surfaces (PES) of a number of model and realistic systems where intruders exist and for molecules in their ground states with pronounced multireference character. Single reference MBPT and effective Hamiltonian-based multireference MBPT second-order results are also presented for comparisons. The results indicate the smooth performance of our state-specific perturbative formalisms in and around the region of intruders in the PES, indicating their suitability in bypassing intruders. In contrast, the effective Hamiltonian-based MBPT methods behave poorly in the regions of intruders. PMID- 27384148 TI - Competition between Hydrogen Bonding and Proton Transfer during Specific Anion Recognition by Dihomooxacalix[4]arene Bidentate Ureas. AB - Competition between hydrogen bonding and proton transfer reactions was studied for systems composed of electrogenerated dianionic species from dinitrobenzene isomers and substituted dihomooxacalix[4]arene bidentate urea derivatives. To analyze this competition, a second-order ErCrCi mechanism was considered where the binding process is succeeded by proton transfer and the voltammetric responses depend on two dimensionless parameters: the first related to hydrogen bonding reactions, and the second one to proton transfer processes. Experimental results indicated that, upon an increase in the concentration of phenyl substituted dihomooxacalix[4]arene bidentate urea, voltammetric responses evolve from diffusion-controlled waves (where the binding process is at chemical equilibrium) into irreversible kinetic responses associated with proton transfer. In particular, the 1,3-dinitrobenzene isomer showed a higher proton transfer rate constant (~25 M(-1) s(-1)) compared to that of the 1,2-dinitrobenzene (~5 M(-1) s(-1)), whereas the 1,4-dinitrobenzene did not show any proton transfer effect in the experimental conditions employed. PMID- 27384149 TI - Rapid improvement of Clinical Disease Activity Index (CDAI) at 3 months predicts a preferable CDAI outcome at 1 year in active rheumatoid arthritis patients treated with tocilizumab: results from an observational investigation of daily clinical practice. AB - OBJECTIVES: To investigate whether the Clinical Disease Activity Index (CDAI) at three months predicts a preferable CDAI outcome at one year in patients with active rheumatoid arthritis (RA) treated with tocilizumab (TCZ). METHODS: Seventy eight RA patients in the Nagasaki Prefecture, Japan, whose disease activities at baseline were moderate to high as estimated by the CDAI and who had received 8 mg/kg of TCZ every four weeks, were consecutively enrolled in this study from April 2008 to March 2011. The association of the CDAI at three months with that at one year was examined by the Cochran-Armitage test. The variables at baseline and at three months that were predictive of remission or low disease activity (LDA) according to the CDAI at one year were assessed by logistic regression analysis. RESULTS: Most of the patients (40 out of 44: 91%), whose CDAI at three months showed remission or LDA continued to show remission or LDA at one year. Disease activity at three months significantly correlated with the frequency of LDA or remission at one year (p<0.0001). Logistic regression analysis revealed that only remission or LDA at three months as determined by the CDAI was predictive of remission or LDA at one year as determined by the CDAI (odds ratio 33.2, p<0.0001). CONCLUSIONS: A preferable clinical outcome as estimated by the CDAI at one year in active RA patients treated with TCZ is predicted by the CDAI at three months, suggesting that the treat-to-target strategy carried out using the CDAI can be used in clinical practice in these patients. PMID- 27384151 TI - Sealing procedures for preterm prelabour rupture of membranes. AB - BACKGROUND: Preterm prelabour rupture of the membranes (PPROM) complicates approximately 2% of pregnancies and can be either spontaneous or iatrogenic in nature. Complications of PPROM include prematurity, chorioamnionitis, neonatal sepsis, limb position defects, respiratory distress syndrome, pulmonary hypoplasia chronic lung disease, periventricular leukomalacia and intraventricular haemorrhage.A number of different sealing techniques have been employed which aim to restore a physical barrier against infection and encourage the re-accumulation of amniotic fluid. Routine use of sealants is currently not recommended due to a lack of sufficient evidence to support the safety and effectiveness of such interventions. OBJECTIVES: To assess the effects of sealing techniques following PPROM against each other, or versus standard care (including no sealant), on maternal and neonatal outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 May 2016) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and quasi randomised controlled trials comparing different techniques for sealing preterm prelabour ruptured membranes. Cluster-randomised trials and trials using a cross over design were not eligible for inclusion in this review. We planned to include abstracts when sufficient information was provided. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and assessed trial quality. Two review authors independently extracted data. Data were checked for accuracy. MAIN RESULTS: We included two studies (involving 141 women - with data from 124 women). We considered both studies as being at high risk of bias. Meta analysis was not possible because the included studies examined different interventions (both in comparison with standard care) and reported on few, but different, outcomes. One study compared cervical adapter (mechanical sealing), and the other study examined an immunological membrane sealant. Neither of the included studies reported on this review's primary outcome of interest - perinatal mortality. Similarly, data were not reported for the majority of this review's secondary infant and maternal outcomes. Cervical adapter (mechanical sealing) versus standard care (one study, data from 35 participants)No data were reported for this review's primary outcome - perinatal mortality. Data were reported for few of this review's infant or maternal secondary outcomes.There was no clear difference between the mechanical sealing group and the standard care control in relation to the incidence of neonatal sepsis (risk ratio (RR) 1.19, 95% confidence interval (CI) 0.28 to 5.09 (very low-quality evidence)) or chorioamnionitis (RR 1.19, 95% CI 0.28 to 5.09 (very low-quality evidence)). Oral immunological membrane sealant versus standard care (one study, data from 94 participants)No data were available for perinatal mortality (this review's primary outcome) or for the majority of this review's infant and maternal secondary outcomes. Compared to standard care, the immunological membrane sealant was associated with a reduction in preterm birth less than 37 weeks (RR 0.48, 95% CI 0.34 to 0.68 (very low-quality evidence)) and a reduction in neonatal death (RR 0.38, 95% CI 0.19 to 0.75 (very low-quality evidence)). However, there was no clear difference between groups in terms of neonatal sepsis (RR 0.64, 95% CI 0.28 to 1.46 (very low-quality evidence)) or respiratory distress syndrome (RR 0.64, 95% CI 0.28 to 1.46 (very low-quality evidence)). AUTHORS' CONCLUSIONS: There is insufficient evidence to evaluate sealing procedures for PPROM. There were no data relating to this review's primary outcome (perinatal mortality) and the majority of our infant and maternal secondary outcomes were not reported in the two included studies.There was limited evidence to suggest that an immunological membrane sealant was associated with a reduction in preterm birth at less than 37 weeks and neonatal death, but these results should be interpreted with caution as this is based on one small study, with a high risk of bias, and the intervention has not been tested in other studies.Although midtrimester PPROM is not a rare occurrence, there are only a small amount of published data addressing the benefits and risks of sealing procedures. Most of these studies are retrospective and cohort based and could therefore not be included in our data-analysis.This review highlights the paucity of prospective randomised trials in this area. Current evidence provides limited information both on effectiveness and safety for the interventions described. Given the paucity of high-quality data, we recommend that future research efforts focus on the conduct of randomised trials assessing the effect of promising interventions that have been only evaluated to date in cohort studies (e.g. amniopatch). Future trials should address outcomes including perinatal mortality, preterm birth, neonatal death, respiratory distress syndrome, neonatal sepsis and developmental delay. They should also evaluate maternal outcomes including sepsis, mode of delivery, length of hospital stay and emotional well-being. PMID- 27384150 TI - Why motor proteins team up - Intraflagellar transport in C. elegans cilia. AB - Inside the cell, vital processes such as cell division and intracellular transport are driven by the concerted action of different molecular motor proteins. In C. elegans chemosensory cilia, 2 kinesin-2 family motor proteins, kinesin-II and OSM-3, team up to drive intraflagellar transport (IFT) in the anterograde direction, from base to tip, whereas IFT dynein hitchhikes toward the tip and subsequently drives IFT in the opposite, retrograde direction, thereby recycling both kinesins. While it is evident that at least a retrograde and an anterograde motor are necessary to drive IFT, it has remained puzzling why 2 same polarity kinesins are employed. Recently, we addressed this question by combining advanced genome-engineering tools with ultrasensitive, quantitative fluorescence microscopy to study IFT with single-molecule sensitivity.(1,2) Using this combination of approaches, we uncovered a differentiation in kinesin-2 function, in which the slower kinesin-II operates as an 'importer', loading IFT trains into the cilium before gradually handing them over to the faster OSM-3. OSM-3 subsequently acts as a long-range 'transporter', driving the IFT trains toward the tip. The two kinesin-2 motors combine their unique motility properties to achieve something neither motor can achieve on its own; that is to optimize the amount of cargo inside the cilium. In this commentary, we provide detailed insight into the rationale behind our research approach and comment on our recent findings. Moreover, we discuss the role of IFT dynein and provide an outlook on future studies. PMID- 27384153 TI - Temperature-dependent annuloselectivity and stereochemistry in the reactions of methanesulfonyl sulfene with imines. AB - The annuloselectivity in the reactions of methanesulfonyl sulfene and imines varies with temperature. At a relatively higher temperature of 20 degrees C, the [2(s) + 2(i)] annulation of different N-alkyl imines occurs exclusively, giving four-membered trans-beta-sultams in up to 69% yields. At a lower temperature of 78 degrees C, the [2(s) + 2(i) + 2(i)] annulation of N-methyl imines takes place specifically, delivering six-membered 1,2,4-thiadiazine 1,1-dioxides, 4-aza-delta sultams, in up to 80% yields, with diverse configurations at the C3, C5, and C6 stereocenters. The trans-stereochemistry involved in the [2(s) + 2(i)] annulations is attributed to the conrotatory ring closure of the thermodynamically stable 2,3-thiazabutadiene-type zwitterionic intermediates, while the diverse stereochemical outcomes in the [2(s) + 2(i) + 2(i)] annulations are caused by the iminium isomerization in the stepwise nucleophilic [4 + 2] annulation between the same zwitterionic intermediates and a second molecule of N methyl imines. PMID- 27384152 TI - miR-7a/b attenuates post-myocardial infarction remodeling and protects H9c2 cardiomyoblast against hypoxia-induced apoptosis involving Sp1 and PARP-1. AB - miRs (microRNAs, miRNAs) intricately regulate physiological and pathological processes. Although miR-7a/b protects against cardiomyocyte injury in ischemia/reperfusion injury, the function of miR-7a/b in myocardial infarction (MI)-induced cardiac remodeling remains unclear. Here, we sought to investigate the function of miR-7a/b in post-MI remodeling in a mouse model and to determine the underlying mechanisms involved. miR-7a/b overexpression improved cardiac function, attenuated cardiac remodeling and reduced fibrosis and apoptosis, whereas miR-7a/b silencing caused the opposite effects. Furthermore, miR-7a/b overexpression suppressed specific protein 1 (Sp1) and poly (ADP-ribose) polymerase (PARP-1) expression both in vivo and in vitro, and a luciferase reporter activity assay showed that miR-7a/b could directly bind to Sp1. Mithramycin, an inhibitor of the DNA binding activity of Sp1, effectively repressed PARP-1 and caspase-3, whereas knocking down miR-7a/b partially counteracted these beneficial effects. Additionally, an immunoprecipitation assay indicated that hypoxia triggered activation of the binding activity of Sp1 to the promoters of PARP-1 and caspase-3, which is abrogated by miR-7a/b. In summary, these findings identified miR-7a/b as protectors of cardiac remodeling and hypoxia-induced injury in H9c2 cardiomyoblasts involving Sp1 and PARP-1. PMID- 27384154 TI - Early Postnatal Manganese Exposure Causes Lasting Impairment of Selective and Focused Attention and Arousal Regulation in Adult Rats. AB - BACKGROUND: Studies in children and adolescents have associated early developmental manganese (Mn) exposure with inattention, impulsivity, hyperactivity, and oppositional behaviors, but causal inferences are precluded by the correlational nature of the data and generally limited control for potential confounders. OBJECTIVES: To determine whether early postnatal oral Mn exposure causes lasting attentional and impulse control deficits in adulthood, and whether continued lifelong Mn exposure exacerbates these effects, using a rat model of environmental Mn exposure. METHODS: Neonates were exposed orally to 0, 25 or 50 mg Mn/kg/day during early postnatal life (PND 1-21) or throughout life from PND 1 until the end of the study. In adulthood, the animals were tested on a series of learning and attention tasks using the five-choice serial reaction time task. RESULTS: Early postnatal Mn exposure caused lasting attentional dysfunction due to impairments in attentional preparedness, selective attention, and arousal regulation, whereas associative ability (learning) and impulse control were spared. The presence and severity of these deficits varied with the dose and duration of Mn exposure. CONCLUSIONS: This study is the first to show that developmental Mn exposure can cause lasting impairments in focused and selective attention and arousal regulation, and to identify the specific nature of the impairments. Given the importance of attention and arousal regulation in cognitive functioning, these findings substantiate concerns about the adverse effects of developmental Mn exposure in humans. Citation: Beaudin SA, Strupp BJ, Strawderman M, Smith DR. 2017. Early postnatal manganese exposure causes lasting impairment of selective and focused attention and arousal regulation in adult rats. Environ Health Perspect 125:230-237; http://dx.doi.org/10.1289/EHP258. PMID- 27384155 TI - Association between Metformin Use and Survival in Nonmetastatic Rectal Cancer Treated with a Curative Resection: A Nationwide Population Study. AB - PURPOSE: Metformin is associated with an anticancer effect. However, the effects of metformin in rectal cancer are controversial. This study investigated the impact of metformin on the survival of patients with diabetes mellitus and nonmetastatic rectal cancer who underwent curative surgery. MATERIALS AND METHODS: The database was provided by the Korea Center Cancer Registry and National Health Insurance Service of the Republic of Korea. A cohort of patients with newly diagnosed rectal cancer between 2005 and 2011 was identified. Drug exposure was defined as receiving the oral hypoglycemic agent for at least 90 days over the period from 6 months before the initial diagnosis of rectal cancer to the last follow-up. RESULTS: A total of 4,503 patients were prescribed oral hypoglycemic agents and classified as the diabetic group, of which 3,694 patients received metformin for at least 90 days. Unadjusted analyses showed a significantly higher overall survival (hazard ratio, 0.596; 95% confidence interval, 0.506 to 0.702) and rectal cancer-specific survival (hazard ratio, 0.621; 95% confidence interval, 0.507 to 0.760) in the metformin group than in the nonmetformin group. The adjusted overall survival (hazard ratio, 0.631; 95% confidence interval, 0.527 to 0.755) and cancer-specific survival (hazard ratio, 0.598; 95% confidence interval, 0.479 to 0.746) in the group with a medication possession ratio of 80% or greater was significantly higher than in the group with a medication possession ratio of less than 80%. CONCLUSION: Metformin use is associated with overall and cancer-specific survival in diabetic patients with a nonmetastatic rectal cancer treated with a curative resection. PMID- 27384156 TI - Paired Primary and Metastatic Tumor Analysis of Somatic Mutations in Synchronous and Metachronous Colorectal Cancer. AB - PURPOSE: Although the mutation status of KRAS is highly concordant in primary and metastatic lesions, it has not been generalized to other major pathway genes. MATERIALS AND METHODS: In this study, 41 genes were evaluated and the mutational profiles were compared in 46 colorectal cancer patients with paired surgical specimens of primary and metastatic lesions: synchronous (n=27) and metachronous (n=19) lesions. A high-throughput mass spectrometry-based genotyping platform validated by orthogonal chemistry, OncoMap v.4.4, was used to evaluate the formalin-fixed, paraffin-embedded surgical specimens. The patients' demographics, tumor characteristics, and microsatellite instability status were analyzed by a retrospective chart review. RESULTS: In this study,with OncoMap, mutationswere identified in 80.4% of patientswith the following frequency: KRAS (39.1%), TP53 (28.3%), APC (28.3%), PIK3CA (6.5%), BRAF (6.5%), and NRAS (4.3%). Although 19.6% (9/46) of the patients showed no gene mutations, 43.5% (20/46) and 37.0% (17/46) had mutations in one and two or more genes, respectively. The synchronous and metachronous lesions showed similar mutational profiles. Paired samples between primary and metastatic tumors differed in 7.4% (2/27) and 10.5% (2/19) for synchronous and metachronous according to OncoMap. CONCLUSION: These findings indicate the major pathway genes, including KRAS, TP53, APC, PIK3CA, BRAF, and NRAS, are often concordant between the primary and metastatic lesions regardless of the temporal relationship of metastasis. PMID- 27384157 TI - Clinicopathological Features of Low-Grade Thyroid-like Nasopharyngeal Papillary Adenocarcinoma. AB - PURPOSE: Primary low-grade thyroid-like papillary adenocarcinomas are extremely rare neoplasms that generally originate in the nasopharynx. Here, we describe a novel case of a 15-year-old Chinese girl who was diagnosed with low-grade thyroid like papillary adenocarcinoma, including a brief review of the literature to reveal the clinicopathological features of low-grade thyroid-like nasopharyngeal papillary adenocarcinoma. MATERIALS AND METHODS: Immunohistochemistry was used to evaluate the expression of pan-cytokeratin (CKpan), cytokeratin (CK) 7, thyroid transcription factor 1 (TTF-1), vimentin, epithelial membrane antigen (EMA), thyroglobulin, CD15, S100, P40, CK20, CDX-2, glial fibrillary acidic protein (GFAP), and Ki-67. Additionally, in situ hybridization investigation was utilized to identify the presence of small Epstein-Barr virus (EBV)-encoded RNA. RESULTS: Histopathological analysis revealed florid proliferation of papillary structures lined by columnar epithelial cells with fibrovascular cores. Immunohistochemically, the neoplastic cells were positive for CKpan, CK7, TTF-1, vimentin, and EMA, but negative for thyroglobulin, CD15, S100, P40, CK20, CDX-2, and GFAP. The Ki-67-labeling index reached 5% in the most concentrated spot. In situ hybridization for EBV was negative. CONCLUSION: Due to the distinct rarity of low-grade thyroid-like papillary adenocarcinomaswith a favorable clinical outcome, a nationwide effort to raise public awareness of this neoplasm is required. PMID- 27384158 TI - Adjuvant Chemotherapy for Advanced Gastric Cancer in Elderly and Non-elderly Patients: Meta-Analysis of Randomized Controlled Trials. AB - PURPOSE: This study evaluated the benefits of adjuvant chemotherapy on elderly patients with advanced gastric cancer (AGC) using meta-analysis of well-designed randomized controlled clinical studies. MATERIALS AND METHODS: PubMed, Embase, and Cochrane were searched to retrieve clinical studies evaluating the benefits of adjuvant chemotherapy in the elderly with AGC. Hazards ratios (HRs) with 95% confidence intervals (CIs) were pooled across studies using a fixed-effects model. RESULTS: Two studies were included in this meta-analysis to estimate HR for the overall survival (OS), and relapse-free survival (RFS) between adjuvant chemotherapy and surgery in elderly and non-elderly patients. HR for OS in the elderly and non-elderly was 0.745 (95% CI, 0.552 to 1.006, p=0.055) and 0.636 (95% CI, 0.522 to 0.776; p < 0.001), respectively, which showed no heterogeneity regarding HR between the two groups (pinteraction=0.389). HR for RFS in the elderly and non-elderly was 0.613 (95% CI, 0.466 to 0.806; p < 0.001) and 0.633 (95% CI, 0.533 to 0.753; p < 0.001), respectively (pinteraction=0.846). CONCLUSION: Meta-analysis suggests that the benefit of adjuvant chemotherapy to the elderly is not big enough to reach statistical significance while the HR for OS is less than 1 (0.745) and no heterogeneity are observed regarding the HR between the elderly and non-elderly patients. PMID- 27384159 TI - Tumor Stage-Related Role of Radiotherapy in Patients with an External Auditory Canal and Middle Ear Carcinoma. AB - PURPOSE: The purpose of this study was to evaluate the clinical outcomes of patients treated with radiotherapy (RT) for a carcinoma of the external auditory canal (EAC) and middle ear. MATERIALS AND METHODS: The records of 32 patients who received RT from 1990 to 2013 were reviewed retrospectively. The Pittsburgh classification was used to stage all the cancers (early stage, T1/T2 [n=12]; advanced stage, T3/T4 or N positive [n=20]). Twenty-one patients (65.6%) were treated with postoperative RT and 11 patients (34.4%) were treated with definitive RT. The median radiation doses for postoperative and definitive RT were 60 Gy and 64.8 Gy, respectively. Chemotherapy was administered to seven patients (21.9%). RESULTS: The 5-year overall survival and disease-free survival rates for all patients were 57% and 52%, respectively. The disease control rates for the patients with early stage versus advanced stage carcinomawere 55.6% (5/9) and 50% (6/12) in the postoperative RT group and 66.7% (2/3) and 37.5% (3/8) in the definitive RT group, respectively. Overall, 15 cases (14 patients, 46.7%) experienced treatment failure; these failures were classified as local in four cases, regional in one case, and distant in 10 cases. The median follow-up period after RT was 51 months (range, 7 to 286 months). CONCLUSION: Patients with early stage carcinoma achieved better outcomes when definitive RT was used. Advanced stage carcinoma patients experienced better outcomes with postoperative RT. The high rate of distant failure after RT, with or without surgery, reflected the lack of a consensus regarding the best therapeutic approach for treating carcinoma of the EAC and middle ear. PMID- 27384160 TI - Analysis of the Clinicopathological Characteristics of Gastric Cancer in Extremely Old Patients. AB - PURPOSE: Gastric cancer is the third-leading cause of cancer-related death in Korea. As the Korean population is ageing, the number of extremely old patients with this disease is increasing. This study examined the clinicopathological characteristics of gastric cancer in extremely old (over 85 years) patients who received treatment or conservative observations and compared the treatment outcomes according to the treatment modality. MATERIALS AND METHODS: A total of 170 patients over 85 years of age were diagnosed with gastric cancer. Of these, 81 underwent treatment for gastric cancer and 89 received conservative observations. The clinicopathological characteristics of the treatment and conservative groupswere compared. RESULTS: The mean age of the patients was 86.5 years. The conservative group included significantly more patients with older ages, macroscopically advanced cancer and upper-middle located cancer. The overall survival rate of the treatment group was significantly higher than that of the conservative group. The disease-specific mortality rate was significantly lower in the treatment group than in the conservative group. Multivariate analysis revealed the clinical course, alarm sign, and macroscopic classification to be independent prognosis factors. CONCLUSION: By itself, the chronological age should not be used as a strategy to determine whether treatmentwill be administered for gastric cancer. Patients who have early gastric cancer or lower risk preexisting comorbidities should not be discouraged from treatment, even if they are older than 85 years. PMID- 27384162 TI - Treatment of Pulmonary Tumor Embolism from Choriocarcinoma: Extracorporeal Membrane Oxygenation as a Bridge through Chemotherapy. AB - A 22-year-old woman with a 1-month history of shortness of breath that was treated as a case of tuberculosis and pulmonary embolism was referred to the authors' hospital. Because of the hemodynamic instability in this patient, venoarterial extracorporeal membrane oxygenation (ECMO) was administered in the intensive care unit. She underwent a pulmonary embolectomy for the treatment of progressive circulatory collapse secondary to a pulmonary embolism. The histopathologic result was consistent with a metastatic choriocarcinoma. Despite the surgical management, persistent refractory cardiogenic shock occurred. Subsequently, the patient was treated with chemotherapy in the presence of ECMO and responded well to chemotherapy. She was discharged after 3 months. This case suggests that metastatic choriocarcinoma should be considered as a differential diagnosis in women of childbearing age presenting with a pulmonary embolism, and ECMO may be beneficial in patients with pulmonary embolism for bridging to surgical embolectomy and chemotherapy. PMID- 27384161 TI - Concurrent Chemoradiotherapy with Temozolomide Followed by Adjuvant Temozolomide for Newly Diagnosed Glioblastoma Patients: A Retrospective Multicenter Observation Study in Korea. AB - PURPOSE: The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample. MATERIALS AND METHODS: A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively. RESULTS: After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O6 methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5 year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period. CONCLUSION: Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment. PMID- 27384164 TI - Supervised neural computing solutions for fluorescence identification of benzimidazole fungicides. Data and decision fusion strategies. AB - Benzimidazole fungicides (BFs) are a type of pesticide of high environmental interest characterized by a heavy fluorescence spectral overlap which complicates its detection in mixtures. In this paper, we present a computational study based on supervised neural networks for a multi-label classification problem. Specifically, backpropagation networks (BPNs) with data fusion and ensemble schemes are used for the simultaneous resolution of difficult multi-fungicide mixtures. We designed, optimized and compared simple BPNs, BPNs with data fusion and BPNs ensembles. The information environment used is made up of synchronous and conventional BF fluorescence spectra. The mixture spectra are not used in the training nor the validation stage. This study allows us to determine the convenience of fusioning the labels of carbendazim and benomyl for the identification of BFs in complex multi-fungicide mixtures. PMID- 27384163 TI - Asian Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Stromal Tumor. AB - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors originating in the gastrointestinal tract. With the introduction of molecular targeted therapy for GISTs which has yielded remarkable outcomes, these tumors have become a model of multidisciplinary oncological treatment. Although Western clinical guidelines are available for GISTs, such as those published by the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO), the clinical situations in Asian countries are different from those in Western countries in terms of diagnostic methods, surgical approach, and availability of new targeted agents. Accordingly, we have reviewed current versions of several GIST guidelines published by Asian countries (Japan, Korea, China, and Taiwan) and the NCCN and ESMO and discussed the areas of dissensus. We here present the first version of the Asian GIST consensus guidelines that were prepared through a series of meetings involving multidisciplinary experts in the four countries. These guidelines provide an optimal approach to the diagnosis and management of GIST patients in Asian countries. PMID- 27384165 TI - Prediction of air pollutant concentration based on sparse response back propagation training feedforward neural networks. AB - In this paper, we predict air pollutant concentration using a feedforward artificial neural network inspired by the mechanism of the human brain as a useful alternative to traditional statistical modeling techniques. The neural network is trained based on sparse response back-propagation in which only a small number of neurons respond to the specified stimulus simultaneously and provide a high convergence rate for the trained network, in addition to low energy consumption and greater generalization. Our method is evaluated on Hong Kong air monitoring station data and corresponding meteorological variables for which five air quality parameters were gathered at four monitoring stations in Hong Kong over 4 years (2012-2015). Our results show that our training method has more advantages in terms of the precision of the prediction, effectiveness, and generalization of traditional linear regression algorithms when compared with a feedforward artificial neural network trained using traditional back-propagation. PMID- 27384166 TI - Reductions of bacterial antibiotic resistance through five biological treatment processes treated municipal wastewater. AB - Wastewater treatment plants are hot spots for antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs). However, limited studies have been conducted to compare the reductions of ARB and ARGs by various biological treatment processes. The study explored the reductions of heterotrophic bacteria resistant to six groups of antibiotics (vancomycin, gentamicin, erythromycin, cephalexin, tetracycline, and sulfadiazine) and corresponding resistance genes (vanA, aacC1, ereA, ampC, tetA, and sulI) by five bench-scale biological reactors. Results demonstrated that membrane bioreactor (MBR) and sequencing batch reactor (SBR) significantly reduced ARB abundances in the ranges of 2.80~3.54 log and 2.70~3.13 log, respectively, followed by activated sludge (AS). Biological filter (BF) and anaerobic (upflow anaerobic sludge blanket, UASB) techniques led to relatively low reductions. In contrast, ARGs were not equally reduced as ARB. AS and SBR also showed significant potentials on ARGs reduction, whilst MBR and UASB could not reduce ARGs effectively. Redundancy analysis implied that the purification of wastewater quality parameters (COD, NH4 (+)-N, and turbidity) performed a positive correlation to ARB and ARGs reductions. PMID- 27384167 TI - Degradation and ecotoxicity of dye Reactive Black 5 after reductive-oxidative process : Environmental Science and Pollution Research. AB - This research paper describes the study of a reduction-oxidation system using commercial steel wool (Fe0) and H2O2 for degradation of the dye Reactive Black 5 and aromatic compounds in water. The reductive process alone allowed the almost complete removal of color (97 +/- 1 %) after 60 min of reaction. The decrease in spectral area (lambda = 599 nm) associated with the chromophore group indicates breakage of the azo bonds. Moreover, the significant change in UV spectra can be associated with the formation of aromatic amines. Regarding the transformation products, a spectrophotometric method based on the diazotization reaction was employed to identify aromatic amines after reductive process, using sulfanilic acid as a model of aromatic amines. In addition, association with Fenton reagents improved the efficiency in the system with 93 +/- 1 % degradation of intermediates formed during the reductive process. Ecotoxicological analysis revealed that the dye solution, after the reductive and oxidative processes, was not toxic to Lactuca sativa seeds. For Daphnia magna, the EC50 (%) values observed revealed that dye solution has an EC50(%) = 74.1 and after reductive process, the toxicity increased (EC50(%) = 63.5), which might be related to the formation of aromatic amines. However, after the Fenton process, the EC50 (%) was >100. These results demonstrated that the Fenton reaction using steel wool as an iron source was very efficient to decrease color, aromatic transformation products, and the ecotoxicity of Reactive Black 5 in solution. PMID- 27384168 TI - Erratum to: Neurobehavioral deficits and brain oxidative stress induced by chronic low exposure of persistent organic pollutants mixture in adult female rat. PMID- 27384169 TI - Convergence of Afrotherian and Laurasiatherian Ungulate-Like Mammals: First Morphological Evidence from the Paleocene of Morocco. AB - Molecular-based analyses showed that extant "ungulate" mammals are polyphyletic and belong to the two main clades Afrotheria (Paenungulata) and Laurasiatheria (Euungulata: Cetartiodactyla-Perissodactyla). However, paleontological and neontological studies hitherto failed to demonstrate the morphological convergence of African and Laurasian "ungulate" orders. They support an "Altungulata" group including the Laurasian order Perissodactyla and the African superorder Paenungulata and characterized especially by quadritubercular and bilophodont molars adapted for a folivorous diet. We report new critical fossils of one of the few known African condylarth-like mammal, the enigmatic Abdounodus from the middle Paleocene of Morocco. They show that Abdounodus and Ocepeia display key intermediate morphologies refuting the homology of the fourth main cusp of upper molars in Paenungulata and Perissodactyla: Paenungulates unexpectedly have a metaconule-derived pseudohypocone, instead of a cingular hypocone. Comparative and functional dental anatomy of Abdounodus demonstrates indeed the convergence of the quadritubercular and bilophodont pattern in "ungulates". Consistently with our reconstruction of the structural evolution of paenungulate bilophodonty, the phylogenetic analysis relates Abdounodus and Ocepeia to Paenungulata as stem taxa of the more inclusive new clade Paenungulatomorpha which is distinct from the Perissodactyla and Anthracobunidae. Abdounodus and Ocepeia help to identify the first convincing synapomorphy within the Afrotheria-i.e., the pseudohypocone-that demonstrates the morphological convergence of African and Laurasian ungulate-like placentals, in agreement with molecular phylogeny. Abdounodus and Ocepeia are the only known representatives of the early African ungulate radiation predating the divergence of extant paenungulate orders. Paenungulatomorpha evolved in Africa since the early Tertiary independently from laurasiatherian euungulates and "condylarths" such as apheliscids. The rapid early Tertiary radiation of the Afrotheria and Paenungulatomorpha, as illustrated by the Paleocene Moroccan mammals, is concurrent with that of the Laurasiatheria in a general, explosive mammal evolution in both the South and North Tethyan continents following the K/Pg event. PMID- 27384171 TI - Chronic Pain, Quality of Life, and Functional Impairment After Surgery Due to Small Bowel Obstruction. AB - BACKGROUND: Emergency laparotomy is a high-risk procedure regarding short-term outcomes; however, long-term outcomes are not well described. The aim of this study was to determine the frequency of chronic postoperative pain, pain-related functional impairment, and incisional hernias and to evaluate the gastrointestinal quality of life after emergency laparotomy due to small bowel obstruction. METHODS: This study was a questionnaire study, conducted at a major gastrointestinal-surgery department in a single tertiary university hospital in Denmark. Patients who had been through emergency laparotomy due to small bowel obstruction were included in the study. The extent of acute and chronic postoperative pain and the prevalence of incisional hernias were examined with specially designed questionnaires, while the pain quality was assed by the self report version of the S-LANSS-questionnaire. Pain-related functional impairment and quality of life were measured using the AAS and the GIQLI questionnaire, respectively. RESULTS: A total of 90 patients returned the questionnaire (response rate 82 %). Nineteen patients (21 %) suffered from chronic postoperative pain. Seventeen patients (19 %) had pain-related functional impairment as a result of the surgery, and 17 patients (19 %) had an incisional hernia at follow-up. Patients with chronic postoperative pain had significantly lower gastrointestinal quality of life score compared with the remaining study population (109 (IQR 39) vs. 127 (IQR 19), P < 0.001). CONCLUSIONS: Chronic postoperative pain is a common long-term complication after emergency laparotomy, and it is related to decreased quality of life. These results should be confirmed in prospective studies. PMID- 27384170 TI - CENPT bridges adjacent CENPA nucleosomes on young human alpha-satellite dimers. AB - Nucleosomes containing the CenH3 (CENPA or CENP-A) histone variant replace H3 nucleosomes at centromeres to provide a foundation for kinetochore assembly. CENPA nucleosomes are part of the constitutive centromere associated network (CCAN) that forms the inner kinetochore on which outer kinetochore proteins assemble. Two components of the CCAN, CENPC and the histone-fold protein CENPT, provide independent connections from the ~171-bp centromeric alpha-satellite repeat units to the outer kinetochore. However, the spatial relationship between CENPA nucleosomes and these two branches remains unclear. To address this issue, we use a base-pair resolution genomic readout of protein-protein interactions, comparative chromatin immunoprecipitation (ChIP) with sequencing, together with sequential ChIP, to infer the in vivo molecular architecture of the human CCAN. In contrast to the currently accepted model in which CENPT associates with H3 nucleosomes, we find that CENPT is centered over the CENPB box between two well positioned CENPA nucleosomes on the most abundant centromeric young alpha satellite dimers and interacts with the CENPB/CENPC complex. Upon cross-linking, the entire CENPA/CENPB/CENPC/CENPT complex is nuclease-protected over an alpha satellite dimer that comprises the fundamental unit of centromeric chromatin. We conclude that CENPA/CENPC and CENPT pathways for kinetochore assembly are physically integrated over young alpha-satellite dimers. PMID- 27384172 TI - Preoperative Left Portal Vein Embolization for Left Liver Resection in High-Risk Hepatobiliary Malignancy Patients. AB - BACKGROUND: Preoperative portal vein embolization (PVE) is performed for right liver (RL) and sometimes left liver (LL) resection to prevent postoperative surgical complications. METHODS: We retrospectively reviewed 10 patients who underwent preoperative left PVE before LL resection for hepatobiliary malignancies along with 3 propensity score-matched control groups (n = 40 each). RESULTS: Mean patient age was 68.6 +/- 6.9 years. Diagnoses included intrahepatic cholangiocarcinoma (n = 4), perihilar cholangiocarcinoma (n = 3), neuroendocrine carcinoma (n = 1), recurrent cholangiocarcinoma (n = 1), and inflammatory liver mass (n = 1). The reason for left PVE was a large LL >40 % of the total liver volume (TLV) with a major comorbidity or age > 70 years with a poor overall condition. All patients underwent preplanned operations, including LL resection at 1-3 weeks post PVE. The LL volume proportion of the TLV was 44.9 +/- 1.7 and 40.7 +/- 2.3 % before and after PVE; thus, 1-2 weeks post PVE, the kinetic shrinkage rate of the LL was 9.4 +/- 3.3 %, and the kinetic growth rate of the RL was 7.6 +/- 2.7 %. The overall surgical complication rates were 40, 50, and 39.2 % in the left PVE, large LL control, and all three control groups, respectively (p >= 0.727). In contrast, the adjusted rates of major complications were 0 % in the left PVE group versus 36.8 % (p = 0.040), 25.6 % (p = 0.123), and 15.8 % (p = 0.295) in the large-, medium-, and small-sized LL control groups, respectively. CONCLUSIONS: Our experience indicates that left PVE is safe and induces atrophy of the LL effectively. We suggest that it can be a useful option to reduce the risk of postoperative complications in elderly high-risk patients. PMID- 27384173 TI - Interaction of Age at Diagnosis with Transcriptional Profiling in Papillary Thyroid Cancer. AB - BACKGROUND: Age is an important prognostic factor for papillary thyroid cancer (PTC). However, little is known about why advanced age is associated with poor prognosis. The study investigated the changes in transcriptional profiling related to age. METHODS: RNA sequencing data of PTC samples were retrieved from The Cancer Genome Atlas data portal. Spearman's correlation was used to test the association between age and gene expression. Correlation in the same direction to disease severity was considered functionally relevant. Functional enrichment analysis and pathway annotations were performed. RESULTS: There was no correlation between age and thyroid-specific genes, except for a weak, negative association between age and TSHR expression. Among 272 genes with a positive association between gene expression and age, the most prominent alteration was metabolic pathways, particularly glycolysis. Among 482 genes with a negative association between gene expression and age, the most enriched biological process was immune-related functions, particularly natural killer cell-mediated cytotoxicity. CONCLUSIONS: Our analysis characterized the age-associated molecular landscape in PTC. Metabolic alterations and immune dysregulation are probable mechanisms involving in worse prognosis in older patients with PTC. PMID- 27384174 TI - Selective Parathyroid Hormone Venous Sampling in Patients with Persistent or Recurrent Primary Hyperparathyroidism and Negative, Equivocal or Discordant Noninvasive Imaging. AB - BACKGROUND: In patients with persistent (P-PHPT) or recurrent (R-PHPT) primary hyperparathyroidism, preoperative localization is important. Selective parathyroid hormone venous sampling (sPVS) is an invasive technique that can be used to regionalize and/or lateralize the source of PHPT when noninvasive imaging studies are nonlocalizing. The aim of the present study was to assess the role of sPVS in the preoperative evaluation of patients with P-PHPT or R-PHPT and negative, equivocal, or discordant noninvasive imaging localization. METHODS: After IRB-approval a retrospective review of all patients with P-PHPT or R-PHPT and nonlocalizing noninvasive imaging that underwent sPVS from 2000 to 2014 was performed. The location of the source of PHPT at sPVS was predicted by a parathyroid hormone (PTH) gradient and compared to the surgical, pathology, and biochemical follow-up data as the gold standard. Sensitivity and positive predictive value (PPV) were calculated. RESULTS: Of 30 patients who underwent sPVS, 12 patients did not undergo surgical exploration due to negative or non localizing PTH gradient (n = 8) or opted for medical management (n = 4). Of the 18 patients who underwent surgical exploration, 17 (94 %) had a positive PTH gradient and pathologic parathyroid tissue identified at surgery. Sensitivity and PPV of sPVS were 93 and 77 %, respectively, for all surgical cases, 86 and 60.0 % for cervical cases (n = 11), and 100 and 100 % for mediastinal cases (n = 7). Sixteen patients (89 %) were surgically cured. CONCLUSIONS: In patients with P PHPT or R-PHPT and nonlocalizing imaging studies, sPVS is a sensitive test for localizing the source of PHPT when a positive PTH gradient is present. PMID- 27384175 TI - A priori and a posteriori dietary patterns at the age of 1 year and body composition at the age of 6 years: the Generation R Study. AB - Dietary patterns have been linked to obesity in adults, however, not much is known about this association in early childhood. We examined associations of different types of dietary patterns in 1-year-old children with body composition at school age in 2026 children participating in a population-based cohort study. Dietary intake at the age of 1 year was assessed with a food-frequency questionnaire. At the children's age of 6 years we measured their body composition with dual-energy X-ray absorptiometry and we calculated body mass index, fat mass index (FMI), and fat-free mass index (FFMI). Three dietary pattern approaches were used: (1) An a priori-defined diet quality score; (2) dietary patterns based on variation in food intake, derived from principal component-analysis (PCA); and (3) dietary patterns based on variations in FMI and FFMI, derived with reduced-rank-regression (RRR). Both the a priori-defined diet score and a 'Health-conscious' PCA-pattern were characterized by a high intake of fruit, vegetables, grains, and vegetable oils, and, after adjustment for confounders, children with higher adherence to these patterns had a higher FFMI at 6 years [0.19 SD (95 % CI 0.08;0.30) per SD increase in diet score], but had no different FMI. One of the two RRR-patterns was also positively associated with FFMI and was characterized by intake of whole grains, pasta and rice, and vegetable oils. Our results suggest that different a priori- and a posteriori derived health-conscious dietary patterns in early childhood are associated with a higher fat-free mass, but not with fat mass, in later childhood. PMID- 27384176 TI - Recombinant T2 RNase protein of Schistosoma japonicum inhibits expression of alpha-SMA in LX-2 cells. AB - Recombinant T2 RNase glycoprotein, which showed a certain degree of homology to Omega-1 from Schistosoma mansoni eggs, was expressed in adult worms of Schistosoma japonicum, but not in eggs of S. japonicum. The direct biological role of the recombinant T2 RNase protein in activation of hepatic stellate cells (HSCs) remains unknown. In the present study, the immortalized human HSC line (LX 2 cells) was treated with the recombinant T2 RNase protein at indicated concentrations for various time points in vitro. The expression levels of alpha smooth muscle actin (alpha-SMA) and Smad4 were detected by Western blot. The results showed that the recombinant T2 RNase protein significantly diminished the expression levels of alpha-SMA and Smad4 in LX-2 cells. The upregulated expression levels of alpha-SMA and Smad4 by TGF-beta1 in LX-2 cells were both suppressed by the recombinant T2 RNase protein. These data suggest that the recombinant T2 RNase protein may be a potential target of therapeutic strategy for the treatment of hepatic fibrosis. PMID- 27384177 TI - Identification of Eimeria acervulina conoid antigen using chicken monoclonal antibody. AB - In the poultry industry, Eimeria spp. is one of the important pathogens which cause significant economic losses. We have previously generated a chicken monoclonal antibody (mAb), 6D-12-G10, with specificity for an antigen located in the apical cytoskeleton of Eimeria acervulina and with cross-reactive among Apicomplexan parasites, including other Eimeria spp., Toxoplasma, Neospora, and Cryptosporidium spp. Furthermore, the protein of Cryptosporidium parvum recognized by the 6D-12-G10 has been identified as elongation factor-1alpha (EF 1alpha). In the present study, to identify the target molecule of E. acervulina by the mAb, we performed two-dimensional Western blotting analysis. Finally, we found two positive molecules which are identified as EF-1alpha and a related protein. Our previous finding using C. parvum and the results in this study suggest that EF-1alpha could be associated with the invasion facilitated by the cytoskeleton at the apical region of zoites. PMID- 27384179 TI - Understanding the response of pulsed electric field on osteoblast functions in three-dimensional mesh structures. AB - The endogenous electric field plays a determining role in impacting biological functions including communication with the physiological system, brain, and bone regeneration by influencing cellular functions. From this perspective, the objective of the study described here is to elucidate the effect of external electric field under dynamic conditions, in providing a guiding cue to osteoblasts in terms of cell-cell interactions and synthesis of prominent adhesion and cytoskeleton proteins. This was accomplished using pulsed direct current electric field of strength 0.1-1 V/cm. The electric field provided guided cue to the cells to migrate toward cathode. Membrane blebbing or necrosis was nearly absent in the vicinity of cathode at 0.1 and 0.5 V/cm electric field strength. Moreover, a higher cell proliferation as well as higher expression of vinculin and densely packed actin stress fibers was observed. At anode, the cells though healthy but expression of actin and vinculin was less. We underscore for the first time that the biological functionality can be favorably modulated on 3D printed scaffolds in the presence of electric field and under dynamic conditions with consequent positive effect on cell proliferation, growth, and expression level of prominent proteins. PMID- 27384178 TI - The Effect of Antiretroviral Treatment on Health Care Utilization in Rural South Africa: A Population-Based Cohort Study. AB - BACKGROUND: The effect of the rapid scale-up of vertical antiretroviral treatment (ART) programs for HIV in sub-Saharan Africa on the overall health system is under intense debate. Some have argued that these programs have reduced access for people suffering from diseases unrelated to HIV because ART programs have drained human and physical resources from other parts of the health system; others have claimed that the investments through ART programs have strengthened the general health system and the population health impacts of ART have freed up health care capacity for the treatment of diseases that are not related to HIV. To establish the population-level impact of ART programs on health care utilization in the public-sector health system, we compared trends in health care utilization among HIV-infected people receiving and not receiving ART with HIV uninfected people during a period of rapid ART scale-up. METHODS AND FINDINGS: We used data from the Wellcome Trust Africa Centre for Population Health, which annually elicited information on health care utilization from all surveillance participants over the period 2009-2012 (N = 32,319). We determined trends in hospitalization, and public-sector and private-sector primary health care (PHC) clinic visits for HIV-infected and -uninfected people over a time period of rapid ART scale-up (2009-2012) in this community. We regressed health care utilization on HIV status and ART status in different calendar years, controlling for sex, age, and area of residence. The proportion of people who reported to have visited a public-sector primary health care (PHC) clinic in the last 6 months increased significantly over the period 2009-2012, for both HIV-infected people (from 59% to 67%; p<0.001), and HIV-uninfected people (from 41% to 47%; p<0.001). In contrast, the proportion of HIV-infected people visiting a private-sector PHC clinic declined from 22% to 12% (p<0.001) and hospitalization rates declined from 128 to 82 per 1000 PY (p<0.001). For HIV-uninfected people, the proportion visiting a private-sector PHC clinic declined from 16% to 9%, and hospitalization rates declined from 78 to 44 per 1000 PY (p<0.001). After controlling for potential confounding factors, all trends remained of similar magnitude and significance. CONCLUSIONS: Our results indicate that the ART scale-up in this high HIV prevalence community has shifted health care utilization from hospitals and private-sector primary care to public-sector primary care. Remarkably, this shift is observed for both HIV-infected and -uninfected populations, supporting and extending hypotheses of 'therapeutic citizenship' whereby HIV-infected patients receiving ART facilitate primary care access for family and community members. One explanation of our findings is that ART has improved the capacity or quality of primary care in this community and, as a consequence, increasingly met overall health care needs at the primary care level rather than at the secondary level. Future research needs to confirm this causal interpretation of our findings using qualitative work to understand causal mechanisms or quasi experimental quantitative studies to increase the strength of causal inference. PMID- 27384180 TI - Differentiating Simple Hepatic Cysts from Mucinous Cystic Neoplasms: Radiological Features, Cyst Fluid Tumour Marker Analysis and Multidisciplinary Team Outcomes. AB - BACKGROUND: Differentiating hepatic mucinous cystic neoplasms (MCNs) from simple hepatic cysts (SCs) preoperatively is a challenging task. Our aim was to determine whether radiological features on ultrasound scan (USS), CT or MRI, cyst fluid tumour markers, or multidisciplinary team (MDT) outcomes could differentiate MCN from SC. METHODS: A retrospective review of radiological features, cyst fluid tumour marker levels and MDT outcomes in 52 patients was performed. RESULTS: There were 13 patients with MCN, 38 with SC and one ciliated foregut cyst. MCNs were more often solitary (p = 0.006). Although no other individual radiological characteristic on USS, CT or MRI was predictive of MCN, MDT outcomes stating that a cyst was complex in nature were highly predictive (p = 0.0007). Cyst fluid carbohydrate antigen 19-9, carcino-embryonic antigen and cancer antigen 125 were unable to differentiate MCN from SC (p = 0.45, p = 0.49, and p = 0.73, respectively). CONCLUSIONS: MDT outcomes are of greatest value when trying to differentiate MCN from SC, as well as having a solitary cyst on imaging. Conventional cyst fluid tumour markers are unhelpful. All suspicious cystic liver lesions should be discussed pre-operatively by a hepatobiliary MDT to determine the most appropriate surgical approach. PMID- 27384181 TI - Cross-cultural adaptation and validation of the Spanish version of the American Academy of Orthopaedic Surgeons-Foot and Ankle Module (AAOS-FAMsp). AB - BACKGROUND: The current study performed a cross-cultural adaptation to Spanish and examined the internal and external validation of the AAOS-FAM questionnaire. METHODS: A direct translation (English to Spanish) and a reverse translation (Spanish to English) were performed by two independent professional native translators. Cronbach's alpha coefficients were calculated to analyse the internal consistency of the measure. The factor structure and construct validity were analysed after extraction by maximum likelihood (EML); extraction was necessary if the following three requirements were met: accounting for >=10 % of variance, Eigenvalue >1.0 and a scree plot inflexion point. The standard error of measurement and minimal detectable change 90 (MDC90) were calculated. Criterion validity was calculated by analysing the correlation between the American Academy of Orthopaedic Surgeons-Foot and Ankle Module (Spanish version) (AAOS-FAMsp) and Spanish versions of the questionnaires FFI and FHSQ. RESULTS: Regarding internal consistency, Cronbach's alpha was 0.877, and in the test-retest analysis, the ICC ranged between 0.899 and 0.942. Error measures were calculated by MDC90 and SEM, which showed values of 3.444 and 1.476 %, respectively. The analysis demonstrated a goodness of fit chi-squared value of 803.166 (p < 0.001). For criterion validity, the correlation value with FFIsp was r = 0.837 (p < 0.01), while the FHSQsp correlation values with different scales ranged from r = 0.206 (p < 0.01) (physical activity) to r = 0.665 (p < 0.01) (pain). CONCLUSIONS: The results indicate that AAOS-FAMsp has satisfactory psychometric properties, facilitating the inclusion of Spanish-speaking individuals into both research and clinical practice. PMID- 27384182 TI - Feasibility evaluation of hypofractionated radiotherapy with concurrent temozolomide in elderly patients with glioblastoma. AB - BACKGROUND: Although hypofractionated radiotherapy (HFRT) is preferred to conventionally fractionated radiotherapy when treating elderly patients with glioblastoma, the benefits and tolerability of HFRT with concurrent temozolomide (TMZ) remain unknown for such patients. We assessed the feasibility and outcomes of elderly patients with glioblastoma treated with HFRT and concurrent TMZ. METHODS: We retrospectively reviewed the medical records of 11 patients aged >=70 years who were treated with HFRT and concurrent TMZ. All patients had newly diagnosed and histologically confirmed glioblastoma and were treated at our institution between October 2011 and April 2015. The median age was 74 years (range, 70-85 years). Total resection/subtotal resection/biopsy were performed in 2/5/4 patients, respectively. The planning target volume included the T1 enhancing tumor and the resection cavity plus 2-cm margins, and all surrounding edema. The median prescription dose was 35 Gy (range, 35-42.5 Gy), delivered in 10 fractions. Seven patients received TMZ at 150 mg/m2 for 5 days and 4 received TMZ at 75 mg/m2 during HFRT. Overall survival (OS) was defined as the time from surgery to death or the last follow-up. RESULTS: The median follow-up period was 13.2 months. The median OS and progression-free survival (PFS) times were 13.2 and 7.0 months, respectively. One patient experienced grade 4 neutropenia, lymphocytopenia, and thrombocytopenia. No grade 3 or higher nonhematological adverse event was noted. CONCLUSION: Our analysis demonstrated the feasibility of HFRT with concurrent TMZ used to treat elderly patients with glioblastoma. Further prospective clinical trials are needed to define therapies that balance efficacy with tolerability. PMID- 27384183 TI - Biological imaging in clinical oncology: radiation therapy based on functional imaging. AB - Radiation therapy is one of the most effective tools for cancer treatment. In recent years, intensity-modulated radiation therapy has become increasingly popular in that target dose-escalation can be done while sparing adjacent normal tissues. For this reason, the development of measures to pave the way for accurate target delineation is of great interest. With the integration of functional information obtained by biological imaging with radiotherapy, strategies using advanced biological imaging to visualize metabolic pathways and to improve therapeutic index and predict treatment response are discussed in this article. PMID- 27384185 TI - Correction: Esophageal Epithelial-Derived IL-33 Is Upregulated in Patients with Heartburn. AB - [This corrects the article DOI: 10.1371/journal.pone.0154234.]. PMID- 27384184 TI - Alpha-2A Adrenoceptor Agonist Guanfacine Restores Diuretic Efficiency in Experimental Cirrhotic Ascites: Comparison with Clonidine. AB - BACKGROUND: In human cirrhosis, adrenergic hyperfunction causes proximal tubular fluid retention and contributes to diuretic-resistant ascites, and clonidine, a sympatholytic drug, improves natriuresis in difficult-to-treat ascites. AIM: To compare clonidine (aspecific alpha2-adrenoceptor agonist) to SSP-002021R (prodrug of guanfacine, specific alpha2A-receptor agonist), both associated with diuretics, in experimental cirrhotic ascites. METHODS AND RESULTS: Six groups of 12 rats were studied: controls (G1); controls receiving furosemide and potassium canrenoate (G2); rats with ascitic cirrhosis due to 14-week CCl4 treatment (G3); cirrhotic rats treated (over the 11th-14th CCl4 weeks) with furosemide and canrenoate (G4), furosemide, canrenoate and clonidine (G5), or diuretics and SSP002021R (G6). Three rats of each group had their hormonal status and renal function assessed at the end of 11th, 12th, 13th, and 14th weeks of respective treatments.Cirrhotic rats in G3 and G4 gained weight over the 12th-14th CCl4 weeks. In G4, brief increase in sodium excretion over the 11th-12th weeks preceded worsening of inulin clearance and natriuresis (diuretic resistance). In comparison with G4, the addition of clonidine (G5) or guanfacine (G6) to diuretics improved, respectively, sodium excretion over the 11th-12th CCl4 weeks, or GFR and electrolytes excretion over the 13th-14th CCl4 weeks. Natriuretic responses in G5 and G6 were accompanied by reduced catecholamine serum levels. CONCLUSIONS: alpha2A-receptor agonists restore glomerular filtration rate and natriuresis, and delay diuretic-resistant ascites in experimental advanced cirrhosis. Clonidine ameliorates diuretic-dependent natriuresis just for a short time. PMID- 27384187 TI - Botulinum neurotoxin A1 likes it double sweet. PMID- 27384186 TI - Lactoferrin Adsorbed onto Biomimetic Hydroxyapatite Nanocrystals Controlling - In Vivo - the Helicobacter pylori Infection. AB - BACKGROUND: The resistance of Helicobacter pylori to the antibiotic therapy poses the problem to discover new therapeutic approaches. Recently it has been stated that antibacterial, immunomodulatory, and antioxidant properties of lactoferrin are increased when this protein is surface-linked to biomimetic hydroxyapatite nanocrystals. OBJECTIVE: Based on these knowledge, the aim of the study was to investigate the efficacy of lactoferrin delivered by biomimetic hydroxyapatite nanoparticles with cell free supernatant from probiotic Lactobacillus paracasei as an alternative therapy against Helicobacter pylori infection. METHODS: Antibacterial and antinflammatory properties, humoral antibody induction, histopathological analysis and absence of side effects were evaluated in both in vitro and in vivo studies. RESULTS: The tests carried out have been demonstrated better performance of lactoferrin delivered by biomimetic hydroxyapatite nanoparticles combined with cell free supernatant from probiotic Lactobacillus paracasei compared to both lactoferrin and probiotic alone or pooled. CONCLUSION: These findings indicate the effectiveness and safety of our proposed therapy as alternative treatment for Helicobacter pylori infection. PMID- 27384188 TI - Molecular chaperones: providing a safe place to weather a midlife protein-folding crisis. PMID- 27384189 TI - New DUBs on the block. PMID- 27384190 TI - Effects of Brinzolamide, a Topical Carbonic Anhydrase Inhibitor, on Corneal Endothelial Cells. AB - INTRODUCTION: This clinical study aimed to investigate the effect of brinzolamide, a topical carbonic anhydrase inhibitor, on corneal endothelial cells (CECs) in patients with glaucoma using a follow-up clinical study design. METHODS: Patients with primary open-angle glaucoma or ocular hypertension were administrated an ophthalmic solution of either latanoprost alone (LT) as a control (n = 18) or latanoprost plus brinzolamide (LT + BR; n = 16). CECs were examined at baseline and at 4, 12, 24, and 48 weeks in 18 and 16 eyes of the LT and LT + BR groups, respectively, using a non-contact specular microscope. CECs were evaluated by parameters, including cell density (CD), coefficient of variation (CV) in cell size, and percentage hexagonality (Hex). RESULTS: Compared with the baseline intraocular pressure (IOP), the mean IOP in the LT group was significantly reduced at 12 and 24 weeks, whereas that in the LT + BR group was significantly reduced at all time points (P < 0.01). The mean CD, CV, and Hex at baseline were not significantly different between the two groups. No significant time-course changes in CD, CV, or Hex were observed in either group. At 48 weeks, there was no significant difference in the mean CD, CV, or Hex between the two groups. CONCLUSION: Patients treated with LT + BR showed significant IOP reduction. However, the use of brinzolamide in addition to latanoprost had no influence on CECs during the one-year follow-up period. PMID- 27384191 TI - Making Insulin Accessible: Does Inhaled Insulin Fill an Unmet Need? AB - Glycemic control is fundamental to the management of diabetes. However, studies suggest that a significant proportion of people with diabetes, particularly those using insulin, are not achieving glycemic targets. The reasons for this are likely to be multifactorial. The real and perceived risk of hypoglycemia and the need for multiple daily injections are widely recognized as key barriers to effective insulin therapy. Therefore, there is a clear unmet need for a treatment option which can help mitigate these barriers. Alternative methods of insulin administration have been under investigation for several years, and pulmonary delivery has shown the most promise to date. Inhaled Technosphere((r)) Insulin (TI; Afrezza((r)); MannKind Corporation) was approved in 2014 for use as prandial insulin in people with diabetes. TI shows a more rapid onset of action and a significantly faster decline in activity than current subcutaneous rapid-acting insulin analogs (RAAs), and TI is more synchronized to the physiologic timing of the postprandial glucose excursion. This results in lower postprandial hypoglycemia with similar glycemic control compared with RAAs, and less weight gain. Together with the ease of use of the TI inhaler and the reduction in the number of daily injections, these findings imply that TI may be useful in helping to overcome patient resistance to insulin, improve adherence and mitigate clinical inertia in health-care providers, with potential beneficial effects on glycemic control. FUNDING: Writing and editorial support in the preparation of this publication was funded by Sanofi US, Inc., Bridgewater, New Jersey, USA. Funding for the article processing charges for this publication was provided by MannKind Corporation. PMID- 27384192 TI - Perceived Odor-Taste Congruence Influences Intensity and Pleasantness Differently. AB - The role of congruence in cross-modal interactions has received little attention. In most experiments involving cross-modal pairs, congruence is conceived of as a binary process according to which cross-modal pairs are categorized as perceptually and/or semantically matching or mismatching. The present study investigated whether odor-taste congruence can be perceived gradually and whether congruence impacts other facets of subjective experience, that is, intensity, pleasantness, and familiarity. To address these questions, we presented food odorants (chicken, orange, and 3 mixtures of the 2) and tastants (savory-salty and sour-sweet) in pairs varying in congruence. Participants were to report the perceived congruence of the pairs along with intensity, pleasantness, and familiarity. We found that participants could perceive distinct congruence levels, thereby favoring a multilevel account of congruence perception. In addition, familiarity and pleasantness followed the same pattern as the congruence while intensity was highest for the most congruent and the most incongruent pairs whereas intensities of the intermediary-congruent pairs were reduced. Principal component analysis revealed that pleasantness and familiarity form one dimension of the phenomenological experience of odor-taste pairs that was orthogonal to intensity. The results bear implications for the understanding the behavioral underpinnings of perseverance of habitual food choices. PMID- 27384193 TI - Referendum anger with The BMJ is misdirected. PMID- 27384195 TI - Care - The Essence of the Nursing Professional Identity. PMID- 27384194 TI - Drug-Eluting Balloons in the Treatment of Coronary De Novo Lesions: A Comprehensive Review. AB - Drug-eluting balloons (DEBs) have emerged as a new application in percutaneous coronary intervention. DEBs have proven successful in the treatment of in-stent restenosis, but their role in de novo lesions is less clear. This paper provides a review of the current studies where DEBs have been used in coronary de novo lesions, either as part of a DEB-only strategy or in combination with another device, mainly a bare metal stent (BMS). By searching Pubmed and Embase we were able to identify 52 relevant studies, differing in design, intervention, and clinical setting, including patients with small vessel disease, bifurcation lesions, complex long lesions, acute myocardial infarction, diabetes mellitus, and elderly. In 23 studies, a DEB was combined with a BMS, 25 studies used a DEB only strategy with only provisional BMS implantation, and four studies combined a DEB with a drug-eluting stent (DES). In the vast majority of studies, DEB in combination with BMS does not seem to improve clinical or angiographic outcome compared with DES, whereas a DEB-only strategy seems promising, especially when predilatation and geographical mismatch are taken into account. A lower risk of recurrent thrombosis with DEB compared with DES is not evident from the current studies. In conclusion, the main indication for DEB seems to be small vessel disease, especially in clinical scenarios in which a contraindication to dual antiplatelet therapy exists. The main approach should be a DEB-only strategy with only provisional bailout stenting, which has shown interesting results in different clinical scenarios. In general, larger randomized controlled studies with prolonged follow-up comparing DEB with best in class DES are warranted. Technical developments of DEBs including the use of different drugs might potentially improve the efficacy of such treatment. PMID- 27384196 TI - Poor sleep quality in patients with resistant hypertension: is there an association? PMID- 27384197 TI - Letter to the editor. PMID- 27384198 TI - Risk factors for postpartum urinary incontinence. AB - OBJECTIVE: To investigate the risk factors for postpartum urinary incontinence (UI) and its characteristics. METHOD: This was a case-control study with 344 puerperal women (77 cases and 267 controls) with up to 90 days postpartum. In a single session, participants were given a questionnaire with sociodemographic and clinical data and two others that assessed urine leakage, leakage situations, and type of UI. RESULTS: Stress UI was present in 45.5% of the women, incidents of urine leakage several times a day in 44.2%, of which 71.4% were in small amounts and 57.1% when coughing or sneezing. In 70.1% of cases, UI began during pregnancy and remained through the postpartum period. After running a binary logistic regression model, the following factors remained in the final model: UI during pregnancy (OR 12.82, CI 95% 6.94 - 23.81, p<0.0001), multiparity (OR 2.26, CI 95% 1.22 - 4.19, p=0.009), gestational age at birth greater or equal to 37 weeks (OR 2.52, CI 95% 1.16 - 5.46, p=0.02) and constipation (OR 1.94, CI 95% 1.05 - 5.46, p=0.035). CONCLUSION: Most often, UI first appeared during pregnancy and remained through the postpartum period. Urinary incontinence during pregnancy, multiparity, gestational age at birth greater or equal to 37 weeks, and constipation were presented as risk factors. In the studied group, stress UI was more frequent. OBJETIVO: Investigar os fatores de risco para a incontinencia urinaria (IU) no puerperio e as suas caracteristicas. METODO: Trata-se de estudo caso-controle com 344 puerperas (77 casos e 267 controles), com ate 90 dias pos parto. Foi aplicado, em um unico momento, um questionario para os dados sociodemograficos e clinicos, e dois outros para avaliar a perda urinaria, situacoes de perda e o tipo de IU. RESULTADOS: Apresentaram IU de esforco 45,5%, perda urinaria diversas vezes ao dia 44,2%, sendo 71,4% em pequena quantidade e 57,1% ao tossir ou espirrar. Em 70,1% dos casos a IU iniciou-se na gestacao e permaneceu no puerperio. Ao ajustar-se um modelo de regressao logistica binaria, apenas IU na gestacao (OR 12,82, IC 95% 6,94 - 23,81, p<0,0001), multiparidade (OR 2,26, IC 95% 1,22 - 4,19, p=0,009), idade gestacional no parto maior ou igual a 37 semanas (OR 2,52, IC 95% 1,16 - 5,46, p=0,02) e constipacao (OR 1,94, IC 95% 1,05 - 5,46, p=0,035) permaneceram no modelo final. CONCLUSAO: A IU iniciou-se frequentemente na gestacao e permaneceu no puerperio. A presenca de IU na gestacao, multiparidade, idade gestacional no parto maior ou igual a 37 semanas e constipacao foram fatores de risco. No grupo estudado a IU de esforco foi a mais frequente. PMID- 27384199 TI - Preconception health behaviors associated with pregnancy planning status among Brazilian women. AB - OBJECTIVE: The objective of this study is to assess preconception health behaviors among Brazilian women, and analyze the effect of pregnancy planning status in carrying out preconception measures. METHOD: This is a cross-sectional quantitative study conducted with 807 women, of whom 649 had a planned or ambivalent pregnancy. Preconception health behaviors were assessed by the Brazilian version of the London Measure of Unplanned Pregnancy. RESULTS: Preconception health behaviors were performed by only 15.9% of women. Among those who planned their pregnancy, less than half completed a health measure (47.0%); the most common was seeking medical assistance and improving the diet. Multiple logistic regression analysis showed a strong association between the preconception health behaviors and a planned pregnancy (adjusted OR = 16.77; 95% CI: 9.47-29.81). Age over 30 years, paid work, and the time interval between menarche and first sexual intercourse were also associated with completing preconception measures. CONCLUSION: The low frequency of preconception health measures, even among women who planned their pregnancy, indicates the urgency of including preconception care on the agenda of public health policies in Brazil. OBJETIVO: Mensurar a realizacao do preparo pre-concepcional, descrever as medidas adotadas como preparo pre-concepcional e analisar o efeito do planejamento da gravidez na realizacao do preparo pre-concepcional. METODO: Estudo quantitativo, do tipo transversal, conduzido com 807 mulheres, das quais 649 tinham gravidez planejada ou ambivalente. O preparo pre-concepcional foi mensurado a partir do London Measure of Unplanned Pregnancy , versao Brasil. RESULTADOS: O preparo pre concepcional foi realizado por apenas 15,9% das mulheres. Dentre as que planejaram a gravidez, menos da metade realizou algum preparo (47,0%), sendo os mais frequentes ter procurado assistencia medica e mudancas na alimentacao. Analise de regressao logistica multipla mostrou forte associacao entre a realizacao do preparo pre-concepcional e o planejamento da gravidez (ORajustado=16,77; IC95% 9,47-29,81). A idade acima de 30 anos, o trabalho remunerado e o intervalo de tempo entre a menarca e a primeira relacao sexual tambem estiveram associados a realizacao do preparo pre-concepcional. CONCLUSAO: A baixa frequencia de realizacao de preparo pre-concepcional, mesmo entre mulheres com gravidez planejada, indica a urgencia de se incluir o cuidado pre concepcional na agenda de politicas publicas de saude. PMID- 27384200 TI - Quality of life of individuals with cleft lip and palate pre- and post-surgical correction of dentofacial deformity. AB - OBJECTIVE: To assesses the quality of life and the impact of oral health conditions in the pre- and post-surgical correction of dentofacial deformity of individuals with cleft lip and palate. METHOD: Quantitative and prospective study in a referral hospital in the period from June 2011 to May 2013. A total of 50 participants responded the questionnaires World Health Organization Quality of Life - Bref (WHOQOL-Bref) and Oral Health Impact Profile - 14 (OHIP-14), approximately 3 days before and 3 to 12 months after surgery. The "t" test for paired samples and Wilcoxon test were used for statistical analysis with a significance level of 5%. RESULTS: After surgery, differences were found in the domains: Physical, Psychological, Environmental and General Questions of the WHOQOL-Bref and domains: Psychological Discomfort, Psychological Disability, Social Disability, Handicap and Overall Score of OHIP-14. CONCLUSION: Surgical correction of dentofacial deformity improved quality of life and had positive impact of oral health condition. OBJETIVO: Avaliar a qualidade de vida e o impacto das condicoes de saude oral nos periodos pre e pos-correcao cirurgica da deformidade dentofacial de individuos com fissura labiopalatina operada. METODO: Estudo quantitativo e prospectivo, realizado em um hospital de referencia, no periodo de junho de 2011 a maio de 2013. Participaram 50 individuos que responderam aos questionarios World Health Organization Quality of Life - Bref (WHOQOL-Bref) e Oral Health Impact Profile - 14 (OHIP-14), aproximadamente 3 dias antes e entre 3 e 12 meses apos a cirurgia. Os testes "t" para amostras pareadas e de Wilcoxon foram usados para analise estatistica, com nivel de significancia de 5%. RESULTADOS: Apos a cirurgia, foram encontradas diferencas nos dominios: Fisico, Psicologico, Meio Ambiente e nas Questoes Gerais do WHOQOL-Bref e nos dominios: Desconforto Psicologico, Limitacao Psicologica, Limitacao Social, Incapacidade e no Escore Geral do OHIP-14. CONCLUSAO: A correcao cirurgica da deformidade dentofacial propiciou melhora da qualidade de vida e impacto positivo da condicao da saude oral. PMID- 27384201 TI - Paradox of life among survivors of bladder cancer and treatments. AB - OBJECTIVE: To interpret the meanings attributed to the experience of bladder cancer among survivors in therapeutic follow-up. METHOD: Qualitative methodological approach, based on medical anthropology and narrative methodology. After approval by the research ethics committee of a public university hospital, data were collected from January 2014 to February 2015, by means of recorded semi structured interviews, direct observation and field journal entries on daily immersion with a group of six men and six women, aged between 57 and 82 years, in therapeutic follow-up. Narratives were analyzed by means of inductive thematic analysis. RESULTS: The meanings revealed difficulties with the processes of disease and treatment, such as breakdown of normal life, uncertainty about the future due to possible recurrence of the disease, difficulty with continuity of care and emotional control, relating it to conflicting ways of understanding the present life. Thus, the meaning of this narrative synthesis is paradox. CONCLUSION: Interpretation of the meaning of experience with bladder cancer among patients provides nurses with a comprehensive view of care, which encompasses biological, psychological and social dimensions, and thereby systematizes humanized care. OBJETIVO: Interpretar o significado atribuido a experiencia do cancer de bexiga entre sobreviventes em seguimento terapeutico. METODO: Empregou se a abordagem metodologica qualitativa, embasado pela antropologia medica e metodo narrativo. Apos aprovacao do Comite de Etica, os dados foram coletados de janeiro 2014 a fevereiro de 2015, por meio de entrevistas semiestruturadas gravadas, observacao direta e registros no diario de imersao com grupo de seis homens e seis mulheres, entre 57 e 82 anos, em seguimento terapeutico em um hospital publico universitario. As narrativas foram analisadas por meio da analise tematica indutiva. RESULTADOS: Os sentidos revelam as dificuldades com o processo da doenca e do tratamento, como rupturas na vida, futuro incerto pela possibilidade de recidiva da doenca, continuidade do tratamento e controle emocional, relacionando-se com as ponderacoes contraditorias da vida atual. Assim, o significado desta sintese narrativa e de paradoxo. CONCLUSAO: A interpretacao do significado da experiencia com cancer de bexiga entre os adoecidos permite ao enfermeiro um olhar integralizado do cuidado que perpasse as dimensoes biopsicossociais dos adoecidos e, com isso, sistematize a assistencia de maneira humanizada. PMID- 27384202 TI - [Not Available]. AB - OBJECTIVE: To analyze basic self-care conditioning factors and quality of life associated with health, relating them to self-care capacity among individuals in the preoperative period of coronary artery bypass graft surgery. METHOD: Descriptive study with a quantitative approach, theoretically and methodologically anchored in the Self-care Deficit Nursing Theory. Data were collected between March and August 2013, using the Self-care Assessment Scale and the Medical Outcomes 36 Item Short Form Health Survey. RESULTS: There was a correlation between self-care capacity and quality of life in the preoperative period of coronary artery bypass graft surgery. CONCLUSION: Among participants of this study, a reduction in quality of life may have occurred due to the presence of noncommunicable diseases; nevertheless, individuals sought the best ways to care for themselves. PMID- 27384203 TI - Care production for tuberculosis cases:analysis according to the elements of the Chronic Care Model. AB - OBJECTIVE: To analyze the care provided to tuberculosis cases in primary health care services according to the elements of the Chronic Care Model. METHOD: Cross sectional study conducted in a capital city of the northeastern region of Brazil involving 83 Family Health Strategy professionals.A structured tool adapted to tuberculosis-related care in Brazil was applied.Analysis was based on the development of indicators with capacity to produce care varying between limited and optimum. RESULTS: The organization of care for tuberculosis and supported self-care presented reasonable capacity.In the coordination with the community, the presence of the community agent presented optimum capacity.Partnership with organizations of the community and involvement of experts presented limited capacity.The qualification of professionals, the system for scheduling and monitoring tuberculosis in the community, and the clinical information system presented basic capacity. CONCLUSION: The capacity of the primary health care services to produce tuberculosis-related care according to the elements of the Chronic Care Model is still limited.Overcoming the fragmentation of care and prioritizing a systemic operation between actions and services of the health care network remains as a major challenge. OBJETIVO: Analisar,segundo os elementos doChronicCareModel,a producao do cuidado aos casos de tuberculose nos servicos de Atencao Primaria a Saude. METODO: Estudo transversal, realizado em capital do nordeste brasileiro, envolvendo 83 profissionais da Estrategia Saude da Familia. Aplicou-se um instrumento estruturado, adaptado para atencao a tuberculose no Brasil. A analise pautou-se na construcao de indicadores, cujacapacidade para producao de cuidados variou entre limitada a otima. RESULTADOS: A organizacao da atencao a tuberculose e o autocuidado apoiado apresentaram capacidade razoavel. Na articulacao com a comunidade, a presencadoagente comunitario de saude apresentou capacidade otima. A parceria com organizacoes da comunidade e o envolvimento de especialistas obtiveram capacidade limitada. A capacitacao dos profissionais, o sistema de agendamento e monitoramento da tuberculose na comunidade e o sistema de informacao clinica alcancaram capacidade basica. CONCLUSAO: A capacidade dos servicos da Atencao Primaria a Saude para producao do cuidado aos casos de tuberculose,segundo os elementos doChronicCareModel,ainda e limitada.Superar a fragmentacao do cuidado e priorizar um funcionamento sistemico entre acoes e servicos da rede de atencao a saude e ainda um grande desafio. PMID- 27384204 TI - Evaluation of the implementation of the directly observed treatment strategy for tuberculosis in a large city. AB - OBJECTIVE: To assess the degree of implementation of the Directly Observed Treatment, Short-course - DOTS for tuberculosis (TB) in a large city. METHOD: Assessment of the implementation of the logic model, whose new cases of infectious pulmonary TB were recruited from specialized clinics and followed-up in basic health units. The judgment matrix covering the five components of the DOTS strategy were used. RESULTS: The result of the logic model indicates DOTS was partially implemented. In external, organizational and implementation contexts, the DOTS strategy was partially implemented; and, the effectiveness was not implemented. CONCLUSION: The partial implementation of the DOTS strategy in the city of Manaus did not reflect in TB control compliance, leading to low effectiveness of the program. OBJETIVO: Avaliar o grau de implantacao da estrategia de tratamento diretamente observado (Directly Observed Treatment, Short-course - DOTS) para tuberculose (TB) em um municipio de grande porte. METODO: Avaliacao de implantacao por meio de modelo logico, cujos casos novos de TB pulmonar bacilifera foram recrutados em ambulatorios especializados e acompanhados nas unidades basicas de saude. Utilizou-se matriz de julgamento que abrange os cinco componentes da estrategia DOTS. RESULTADOS: O resultado do modelo logico indica DOTS implantada parcialmente. Nos contextos externo, organizacional e de implantacao, a estrategia DOTS esta implantada parcialmente; e, na efetividade nao esta implantada. CONCLUSAO: A implantacao parcial da estrategia DOTS, na cidade de Manaus, reflete na nao conformidade do controle da TB, levando a baixa efetividade do programa. PMID- 27384205 TI - Hepatitis B vaccination coverage in patients with diabetes mellitus. AB - OBJECTIVE: Analyze the factors associated with full hepatitis B vaccination (three doses) in patients with diabetes mellitus. METHOD: Cross-sectional study, conducted in a health unit in a city in the state of Sao Paulo, with 255 patients on outpatient follow-up, in 2014. Data were obtained from the computerized system of the Municipal Health Department and via a structured questionnaire. A logistic regression model was used for analysis. RESULTS: Full hepatitis B vaccination was noted in 13.7% of the patients and shown to be directly associated with their educational level (OR=1.30; CI: 1.07-1.57) and current or previous work as a health professional (OR=3.21; CI: 1.16-8.89). CONCLUSION: Hepatitis B vaccination coverage was found to be low in patients with diabetes mellitus, indicating their vulnerability to this serious and potentially fatal disease. Higher educational level and working in the field of health were associated with better vaccination coverage. OBJETIVO: Analisar os fatores associados a vacinacao completa contra hepatite B (3 doses) em pacientes com diabetes mellitus. METODO: Estudo transversal, realizado em uma Unidade de Saude, de uma cidade do interior paulista, com 255 pacientes em seguimento ambulatorial, em 2014. Os dados foram obtidos no sistema informatizado da Secretaria Municipal de Saude e por meio de um questionario estruturado e, para analise, modelo de regressao logistica. RESULTADOS: Vacinacao completa contra hepatite B foi observada em 13,7% dos pacientes e mostrou-se diretamente associada ao nivel de escolaridade (OR=1,30; IC: 1,07-1,57) e ao trabalho atual ou pregresso como profissional da saude (OR=3,21; IC: 1,16-8,89). CONCLUSAO: A cobertura vacinal contra hepatite B mostrou-se baixa em pacientes com diabetes mellitus, evidenciando a vulnerabilidade a essa doenca grave e potencialmente fatal. Maior escolaridade e o trabalho na area da saude foram associados a melhor cobertura vacinal. PMID- 27384206 TI - Phlebitis associated with peripheral intravenous catheters in adults admitted to hospital in the Western Brazilian Amazon. AB - OBJECTIVE: To identify the presence of phlebitis and the factors that influence the development of this complication in adult patients admitted to hospital in the western Brazilian Amazon. METHOD: Exploratory study with a sample of 122 peripheral intravenous catheters inserted in 122 patients in a medical unit. Variables related to the patient and intravenous therapy were analyzed. For the analysis, we used chi-square tests of Pearson and Fisher exact test, with 5% significance level. RESULTS: Complication was the main reason for catheter removal (67.2%), phlebitis was the most frequent complication (31.1%). The mean duration of intravenous therapy use was 8.81 days in continuous and intermittent infusion (61.5%), in 20G catheter (39.3%), inserted in the dorsal hand vein arc (36.9 %), with mean time of usage of 68.4 hours. The type of infusion (p=0.044) and the presence of chronic disease (p=0.005) and infection (p=0.007) affected the development of phlebitis. CONCLUSION: There was a high frequency of phlebitis in the sample, being influenced by concomitant use of continuous and intermittent infusion of drugs and solutions, and more frequent in patients with chronic diseases and infection. OBJETIVO: Identificar a presenca de flebite e os fatores que influenciam o desenvolvimento desta complicacao em pacientes adultos internados em hospital da Amazonia Ocidental Brasileira. METODO: Estudo exploratorio, com amostra de 122 cateteres intravenosos perifericos instalados em 122 pacientes de uma unidade de clinica medica. Foram analisadas variaveis relacionadas ao paciente e a terapia intravenosa. Para a analise utilizaram-se os testes de Qui-quadrado de Pearson e Exato de Fisher, com nivel de significancia de 5%. RESULTADOS: A complicacao foi o principal motivo da retirada do cateter (67,2%), e a flebite a complicacao mais frequente (31,1%). O tempo medio de uso de terapia intravenosa foi de 8,81 dias, em infusao continua e intermitente (61,5%), em cateter calibre 20G (39,3%), inseridos nas veias do arco dorsal da mao (36,9%), com media de tempo de permanencia de 68,4 horas. O tipo de infusao (p=0,044) e a presenca de doenca cronica (p=0,005) e de infeccao (p=0,007) influenciaram o desenvolvimento de flebite. CONCLUSAO: Houve alta frequencia de flebite na amostra estudada, sendo influenciada pelo emprego concomitante de infusao continua e intermitente de farmacos e solucoes, e mais frequente em pacientes com doencas cronicas e infeccao. PMID- 27384207 TI - Subset of nursing diagnoses for the elderly in Primary Health Care. AB - OBJECTIVE: To develop a subset of nursing diagnoses for the elderly followed in primary health care based on the bank of terms for clinical nursing practice with the elderly, in the International Classification for Nursing Practice (ICNP(r)) version 2013, and on the Model of Nursing Care. METHOD: Descriptive study developed in sequential steps of construction and validation of the bank of terms, elaboration of the nursing diagnoses based on the guidelines of the International Council of Nurses and the bank of terms, and categorization of diagnostics according to the Care Model. RESULTS: The total of 127 nursing diagnoses were elaborated from 359 validated terms, distributed according to the basic human needs. CONCLUSION: It is expected that these diagnoses will form the basis for the planning of nursing care and use of a unified language for documentation of clinical nursing practice with the elderly in primary care. OBJETIVO: Desenvolver um subconjunto de diagnosticos de enfermagem para idosos acompanhados na Atencao Primaria a Saude, com base no banco de termos para a pratica clinica de enfermagem com idosos, na Classificacao Internacional para a Pratica de Enfermagem (CIPE(r)) Versao 2013 e no Modelo de Cuidados de Enfermagem. METODOS: Pesquisa descritiva, desenvolvida em etapas sequenciadas de construcao e validacao do banco de termos, elaboracao dos enunciados de diagnosticos de enfermagem, com base nas diretrizes do Conselho Internacional de Enfermeiros e no banco de termos, e categorizacao dos diagnosticos segundo o Modelo de Cuidados. RESULTADOS: A partir de 359 termos validados foram elaborados 127 enunciados de diagnosticos de enfermagem, distribuidos segundo as necessidades humanas fundamentais. CONCLUSAO: Acredita-se que esses enunciados servirao de base para o planejamento dos cuidados de enfermagem e utilizacao de uma linguagem unificada para a documentacao da pratica clinica de enfermagem com idosos na atencao primaria. PMID- 27384208 TI - Sleep, quality of life and mood of nursing professionals of pediatric intensive care units. AB - OBJECTIVE: To assess sleep, quality of life and mood of nursing professionals of pediatric intensive care units. METHOD: Quantitative, cross-sectional and descriptive study. Professionals grouped by morning, afternoon and evening shifts were assessed by means of the instruments: Morningness-Eveningness Questionnaire; Pittsburgh Sleep Quality Index; Epworth Sleepiness Scale; Generic questionnaire for the assessment of quality of life (SF-36); Beck Depression Inventory; Beck Anxiety Inventory; State-Trait Anxiety Inventory. RESULTS: Sample consisted of 168 professionals, with prevalence of neutral typology (57.49%). There was no statistical significance regarding sleep, despite scores showing a poor quality of sleep and excessive daytime sleepiness for the three shifts. Quality of life did not reveal any statistical significance, but in the field "social role functioning" of the evening shift, a lower score was observed (p<0.007). There was no statistical significance regarding levels of anxiety and depression. CONCLUSION: The results suggest that these professionals may present sleeping problems, but they do not have lower scores of quality of life or mood disorders. Likely explanations for these findings may include an adaptation to their work type over time and the fact that working with children is rewarding. OBJETIVO: Avaliar sono, qualidade de vida e humor em profissionais de enfermagem em Unidades de Terapia Intensiva Infantil. METODO: Estudo quantitativo, transversal e descritivo. Profissionais agrupados por turnos matutino, vespertino e noturno foram avaliados pelos instrumentos: Questionario de identificacao Matutinidade Vespertinidade; Indice de qualidade do sono de Pittsburgh; Escala de sonolencia Epworth; Questionario generico de avaliacao de qualidade de vida - SF-36; Inventario de depressao de Beck; Inventario de ansiedade de Beck; Inventario de ansiedade Traco-Estado. RESULTADOS: Amostra composta por 168 profissionais, predominando tipologia neutra, 57,49%. Nao houve significancia estatistica quanto ao sono, apesar dos escores mostrarem qualidade ruim e sonolencia diurna excessiva para os tres turnos. A qualidade de vida nao denotou diferenca estatistica, mas no dominio "aspecto social" do turno noturno, observou-se escore pior (p<0,007). Nao houve significancia estatistica nos niveis de ansiedade e depressao. CONCLUSAO: Os resultados sugerem que estes profissionais podem apresentar problemas no sono, entretanto nao apresentam escores mais baixos de qualidade de vida ou transtornos do humor. Possiveis explicacoes para estes achados sao que haja uma adaptacao ao regime de trabalho ao longo do tempo e que trabalhar com criancas seja recompensador. PMID- 27384209 TI - Outsourcing and "dismantling" of steady jobs at hospitals. AB - OBJECTIVE: To relate hospitals' organizational structure as the core of a web of outsourced services and flexible employment bonds among healthcare professionals in the context of finance capitalism, analyzing work arrangements based mainly on the type of employment bond. METHOD: Qualitative research through ethnography, interviews, data analysis, and case studies. The case studies were concentrated in 3 hospitals located in the Sao Paulo metropolitan region under different management types: public administration; outsourced administration via a healthcare social organization (HSO); and private administration. RESULTS: This study highlights a trend in outsourcing, dismantling of steady jobs, and shaping working relations asymmetrically in terms of healthcare professions. CONCLUSION: These aspects are characteristic of contemporary capitalism and post-Fordist work organization. In this context, the state under sponsorship cripples the very existence of an effective human resources policy, creating a favorable environment for outsourcing and flexibility of employment bonds among healthcare workers. OBJETIVO: Relacionar a estrutura organizativa dos hospitais como nucleo de uma rede de servicos subcontratados e a flexibilizacao dos vinculos contratuais dos profissionais de saude no contexto de capitalismo financeirizado, analisando os regimes de trabalho condicionados centralmente pelo vinculo empregaticio. METODO: Pesquisa qualitativa atraves de etnografia, realizacao de entrevistas, analise de dados e utilizacao de estudo de caso. Os estudos de caso concentram-se em tres hospitais localizados Regiao Metropolitana de Sao Paulo com gestoes distintas: administracao publica; administracao terceirizada para Organizacao Social de Saude (OSS); e administracao privada. RESULTADOS: Destacamos a tendencia da terceirizacao, do desmonte do emprego estavel e a conformacao de relacoes trabalhistas assimetricas para as profissoes em saude. CONCLUSAO: Esses aspectos sao caracteristicos do periodo do capitalismo contemporaneo e da organizacao pos-fordista do trabalho. Nesse contexto, o subfinanciamento do Estado inviabiliza uma politica de recursos humanos efetiva, configurando o ambiente propicio para as terceirizacoes e flexibilidade do vinculo empregaticio para os trabalhadores de saude. PMID- 27384210 TI - Costs of topical treatment of pressure ulcer patients. AB - OBJECTIVE: To evaluate the costs of a topical treatment of pressure ulcer (PU) patients in a hospital unit for treatment of chronic patients in 2014. METHOD: This is an activity-based costing study. This method encompasses the identification, measurement and pricing of physical and human resources consumed for dressings. RESULTS: Procedure costs varied between BRL 16.41 and BRL 260.18. For PUs of the same category, of near areas and with the same type of barrier/adjuvant, the cost varied between 3.5% and 614.6%. For most dressings, the cost increased proportionally to the increase of the area and to the development of PU category. The primary barrier accounted for a high percentage of costs among all items required to the application of dressings (human and material resources). Dressings applied in sacral PUs had longer application times. CONCLUSION: This study allowed us to understand the costs involved in the treatment of PUs, and it may support decision-makers and other cost-effectiveness studies. OBJETIVO: Realizar uma avaliacao do custo do tratamento topico de pacientes com ulceras por pressao (UP), em uma unidade hospitalar de atendimento a pacientes cronicos no ano de 2014. METODO: Trata-se de um estudo de custos baseado no Sistema de custeio Baseado em Atividades. Este metodo contempla a identificacao, mensuracao e precificacao dos recursos fisicos e humanos consumidos para a realizacao de curativos. RESULTADOS: Os custos dos procedimentos variaram de R$16,41 a R$260,18. Para UP de mesma categoria, de areas aproximadas e mesmo tipo de cobertura/adjuvante, a variacao entre os custos foi de 3,5% a 614,6%. Para a maioria dos curativos, o custo aumentou proporcionalmente ao aumento da area e a progressao da categoria das UP. A cobertura primaria representou elevado percentual nos custos entre todos os itens necessarios para realizar os curativos (recursos humanos e materiais). Os curativos realizados nas UP sacrais foram os que apresentaram maiores tempos para execucao. CONCLUSAO: Este estudo permitiu conhecer os custos envolvidos no tratamento das UP e pode fornecer subsidios para os tomadores de decisao, assim como para a realizacao de estudos de custo-efetividade. PMID- 27384211 TI - Sepsis in a university hospital: a prospective study for the cost analysis of patients' hospitalization. AB - OBJECTIVE: To estimate the cost of hospitalization of patients with severe sepsis or septic shock admitted or diagnosed in the Urgent and Emergency sector at a university hospital and followed until the clinical outcome. METHOD: An epidemiological, prospective, observational study conducted in a public hospital in southern Brazil for the period of one year (August 2013 to August 2014). Sepsis notification forms, medical records and data of the cost sector were used for the collection of clinical and epidemiological data. RESULTS: The sample comprised 95 patients, resulting in a total high cost of hospitalization (R$ 3,692,421.00), and an average of R$ 38,867.60 per patient. Over half of the total value of the treatment of sepsis (R$ 2,215,773.50) was assigned to patients who progressed to death (59.0%). The higher costs were related to discharge, diagnosis of severe sepsis, the pulmonary focus of infection and the age group of up to 59 years. CONCLUSION: The high cost of the treatment of sepsis justifies investments in training actions and institution of protocols that can direct preventive actions, and optimize diagnosis and treatment in infected and septic patients. OBJETIVO: Estimar o custo da internacao de pacientes com sepse grave ou choque septico admitidos ou diagnosticados no setor de Urgencias e Emergencias de um hospital universitario e seguidos ate o desfecho clinico. METODO: Estudo epidemiologico, prospectivo e observacional, realizado em um hospital publico do sul do Brasil, no periodo de 1 ano (agosto de 2013 a agosto de 2014). A coleta dos dados clinico-epidemiologicos utilizou fichas de notificacao de sepse, prontuarios e dados do setor de custos. Foi realizada analise de tendencia central, dispersao e quartis dos custos das internacoes. RESULTADOS: Amostra composta por 95 pacientes que totalizaram elevado custo da internacao (R$ 3.692.421,00), com media de R$ 38.867,60 por paciente. Mais da metade do valor total do tratamento da sepse (R$ 2.215.773,50) destinou-se a pacientes que evoluiram a obito (59,0%). Os maiores custos foram relacionados a alta, ao diagnostico de sepse grave, ao foco infeccioso pulmonar e a faixa etaria ate os 59 anos. CONCLUSAO: O elevado custo com o tratamento da sepse justificam investimentos em acoes de capacitacao e instituicao de protocolos que possam direcionar acoes preventivas, otimizar o diagnostico e a terapeutica em pacientes infectados e septico. PMID- 27384212 TI - Development and validation of educational technology for venous ulcer care. AB - OBJECTIVE: To develop and validate an educational technology venous ulcers care. METHOD: Methodological study conducted in five steps: Situational diagnosis; literature review; development of texts, illustrations and layout; apparent and content validity by the Content Validity Index, assessment of Flesch Readability Index; and pilot testing. RESULTS: The developed technology was a type of booklet entitled Booklet for Venous Ulcers Care, consisting of seven topics: Diet and food intake, walking and light exercise, resting with elevated leg, bandage care, compression therapy, family support, and keeping healthy habits. The apparent validity revealed minimal agreement of 85.7% in the clarity and comprehensibility. The total content validity index was 0.97, the Flesch Readability Index was 75%, corresponding to the reading "fairly easy". The pilot test showed that 100% of people with venous ulcers evaluated the text and the illustrations as understandable, as appropriate. CONCLUSION: The educational technology proved to be valid for the appearance and content with potential for use in clinical practice. OBJETIVO: Construir e validar uma tecnologia educativa para cuidados com ulcera venosa. METODO: Estudo metodologico realizado em cinco fases: diagnostico situacional; revisao da literatura; desenvolvimento de textos, ilustracoes e diagramacao; validade de aparencia e de conteudo pelo Indice de Validade de Conteudo, avaliacao do Indice de Legibilidade de Flesch; e teste piloto. RESULTADOS: A tecnologia desenvolvida foi do tipo cartilha intitulada Cartilha para cuidados com ulcera venosa, constituida de sete topicos: Alimentacao, Caminhadas e exercicios leves, Repouso com a perna elevada, Cuidados com o curativo, Terapia compressiva, Apoio familiar, e manter habitos saudaveis. A validade aparente revelou concordancia minima de 85,7% na clareza e compreensibilidade. O Indice de Validade de Conteudo total foi de 0,97, o Indice de legibilidade de Flesch foi de 75%, o que correspondeu a leitura "razoavelmente facil". O teste piloto revelou que 100% das pessoas com ulcera venosa avaliaram o texto como compreensivo e as ilustracoes, como adequadas. CONCLUSAO: A tecnologia educativa mostrou-se valida quanto a aparencia e ao conteudo, com potencial de utilizacao na pratica clinica. PMID- 27384213 TI - Palliative care and nursing in dissertations and theses in Portugal: a bibliometric study. AB - OBJECTIVE: To identify the academic scientific production on palliative care in master dissertations and PhD theses carried out by nurses in Portugal. METHOD: A descriptive retrospective study of bibliometric type with search for the abstracts available in repositories of higher education institutions in the period 2000-2014. RESULTS: Of the 1814 papers identified, 249 met the inclusion criteria (ten doctoral theses and 239 master dissertations). The most representative methodological approach was quantitative (31.35%) and the most studied area was family/informal caregiver (20.69%). The most studied target population were the students/health professionals (38.51%). CONCLUSION: The academic scientific production in this area has been growing in spite of the need for continued investment in order to fill the identified gaps. OBJETIVO: Identificar a producao cientifica academica sobre cuidados paliativos nos estudos de mestrados e doutoramentos efetuados por enfermeiros em Portugal. METODO: Estudo descritivo e retrospetivo, do tipo bibliometrico, recorrendo aos resumos disponiveis nos repositorios das instituicoes de ensino superior no periodo 2000 2014. RESULTADOS: Dos 1814 trabalhos identificados, 249 corresponderam aos criterios de inclusao (10 teses de doutoramento e 239 dissertacoes de mestrado). A abordagem metodologica mais representativa e a quantitativa (31,35%), a area mais estudada foi a familia/cuidador informal (20,69%) e a populacao-alvo mais estudada foram os estudantes/profissionais de saude (38,51%). CONCLUSAO: A producao cientifica academica nessa area tem vindo a crescer. Embora exista necessidade de investimento continuo de forma a colmatar as lacunas identificadas. PMID- 27384214 TI - Nursing care for women with pre-eclampsia and/or eclampsia: integrative review. AB - OBJECTIVE: To analyze the available evidence in the literature on nursing care for women with pre-eclampsia and/or eclampsia. METHODS: Integrative review searching for primary studies in the databases PubMed, CINAHL, LILACS and SciELO. RESULTS: The sample size consisted of 17 primary studies published between January 2000 and December 2014, grouped into four categories: standardizing blood pressure measurement technique; training with simulation; instruments for standardization of care and quality of care The main nursing actions were: physical examination, early detection of signs of pre-eclampsia/eclampsia, monitoring of laboratory tests, fetal assessment, qualification and training of professionals. We identified the need for standardization of care from instruments, protocols and blood pressure measurement technique, early identification and treatment of hypertensive crisis through institutional protocols and review of cases and work processes. CONCLUSION: Women with pre eclampsia and/or eclampsia require specific nursing care, which must be guided by care protocols based on scientific evidence. OBJETIVO: Analisar as evidencias disponiveis na literatura sobre assistencia de enfermagem as mulheres com pre eclampsia e/ou eclampsia. METODO: Revisao integrativa cuja busca dos estudos primarios foi realizada nas bases de dados PubMed, CINAHL, LILACS e SciELO. RESULTADOS: Amostra foi composta por 17 estudos primarios, publicados entre janeiro de 2000 e dezembro de 2014, agrupados em quatro categorias: padronizacao da tecnica de mensuracao da pressao arterial; treinamentos com simulacao; instrumentos para padronizacao da assistencia e qualidade da assistencia As principais acoes de enfermagem foram: exame fisico, identificacao precoce de sinais de pre-eclampsia/eclampsia, acompanhamento de exames laboratoriais, avaliacao fetal, capacitacao e treinamento dos profissionais. Identificou-se a necessidade de padronizacao do atendimento a partir de instrumentos e protocolos e da tecnica de afericao da pressao arterial, identificacao e tratamento precoces da crise hipertensiva mediante protocolos institucionais e revisao de casos e processos de trabalho. CONCLUSAO: Mulheres com pre-eclampsia e/ou eclampsia exigem cuidados de enfermagem especificos, os quais devem ser pautados em protocolos de cuidados baseados em evidencias cientificas. PMID- 27384215 TI - Primary health care assessment from the users' perspectives: a systematic review. AB - OBJECTIVE: Analyze the evaluation of the attributes of primary care made by users of basic units of Brazilian health by using PCATool instrument adapted to Brazil. METHOD: A systematic literature review conducted in the PubMed database, IBECS, LILACS, SciELO and BDTD. RESULTS: 4,405 documents were found, selected 23 full texts. After Full reading and application of eligibility criteria, 14 articles were evaluated. The studies showed that primary care performs well in longitudinality attributes, completeness and coordination and worse performance on attributes access first contact, family counseling and community orientation, even in the basic units with the Family Health. CONCLUSION: The users of basic health units assessed as unsatisfactory attributes considered essential for a health care more equitable and competing for user autonomy and social control. It is inferred that there are still obstacles hindering user access to basic health services and care actions are still being developed without favoring user participation and the community context in which they live. OBJETIVO: Analisar a avaliacao dos atributos da Atencao Basica feita por usuarios de unidades basicas de saude brasileiras, mediante utilizacao de adaptacoes do instrumento PCATool para o Brasil. METODO: Revisao sistematica da literatura realizada nas bases de dados Medline/PubMed, LILACS, IBECS, SciELO e BDTD. RESULTADOS: Foram encontrados 4.405 documentos, sendo selecionados 23 textos completos. Apos leitura integral e aplicacao dos criterios de elegibilidade, 14 artigos foram avaliados. Os estudos apontaram que a Atencao Basica tem bom desempenho nos atributos longitudinalidade, integralidade e coordenacao e pior desempenho nos atributos acesso de primeiro contato, orientacao familiar e a orientacao comunitaria, mesmo nas unidades basicas com Saude da Familia. CONCLUSAO: Os usuarios das unidades basicas de saude avaliaram como insatisfatorios atributos considerados fundamentais para uma atencao a saude mais equanime e concorrente para autonomia do usuario e controle social. Infere-se que ainda existem obstaculos que dificultam o acesso dos usuarios aos servicos basicos de saude e que acoes do cuidado ainda estejam sendo desenvolvidas sem privilegiar a participacao do usuario e o contexto comunitario onde vivem. PMID- 27384216 TI - Scientific evidence of dockworker illness to nursing clinical reasoning. AB - OBJECTIVE: To identify scientific evidence of occupational illness of dockworkers published in the literature. METHOD: systematic review of the literature, developed according to the Cochrane method. The databases searched were: Cochrane, LILACS, MEDLINE/PubMed, CINAHL and SciELO. Studies from 1988 to 2014 were selected. The data were analyzed according to the level of evidence and Strengthening the Reporting of Observational Studies in Epidemiology. RESULTS: We included 14 studies, in which 11 (78.6%) were from international journals. The year of 2012 showed greater number of studies. All studies were classified as: Level of Evidence 4, highlighting lung cancer, musculoskeletal and ischemic diseases, causal link in chemical risks. CONCLUSION: The development of preventive measures should especially include chemical exposure of workers applying the clinical reasoning of nurses' environmental knowledge to care for illnesses. OBJETIVO: Identificar evidencias cientificas de adoecimento ocupacional do trabalhador portuario publicadas na literatura. METODO: Revisao sistematica da literatura, construida conforme o metodo Cochrane. As bases de dados pesquisadas foram Cochrane, LILACS, MEDLINE/PubMed, CINAHL e SciELO. Foram selecionados artigos publicados de 1988 a 2014. Os dados foram analisados conforme o Nivel de Evidencia e Strengthening the Reporting of Observational Studies in Epidemiology. RESULTADOS: Foram selecionadas 14 publicacoes, das quais 11 (78,6%) de revistas internacionais. O ano de 2012 reuniu maior numero de publicacoes no periodo de estudo. Todas as publicacoes pertenciam ao Nivel de Evidencia 4, destacando o cancer pulmonar, doencas osteomusculares e isquemicas, com nexo causal nos riscos quimicos. CONCLUSAO: A elaboracao de medidas preventivas deve prever especialmente a exposicao quimica do trabalhador, aplicando ao raciocinio clinico do enfermeiro um conhecimento ambiental para a assistencia aos adoecimentos. PMID- 27384217 TI - Effectiveness of teaching strategies on the development of critical thinking in undergraduate nursing students: a meta-analysis. AB - OBJECTIVE: To evaluate the effectiveness of teaching strategies used for development of critical thinking (CT) in undergraduate nursing students. METHOD: Systematic review with meta-analysis based on the recommendations of the Joanna Briggs Institute . Searches were conducted in the following databases: PubMed, CINAHL, EMBASE, Web of Science, SCOPUS, LILACS, Cochrane CENTRAL, PsycINFO, ERIC, and a database of theses from four continents. The initial selection and evaluation of studies and assessment of methodological quality was performed by two reviewers independently. RESULTS: Twelve randomized clinical trials were included in the study. In the meta-analysis of the four studies included that evaluated the strategy of problem-based learning (PBL), compared to lectures, the effectiveness of PBL was demonstrated with statistical significance (SMD = 0.21 and 95% CI = 0.01 to 0.42; p = 0.0434) for the development of CT in undergraduate nursing students, and the studies were homogeneous (chi-square = 6.10, p = 0.106). CONCLUSION: The effectiveness of PBL was demonstrated in the increase of overall CT scores. Further studies need to be conducted in order to develop, implement and evaluate teaching strategies that are guided in high methodological rigor, and supported in theoretical models of teaching and learning. OBJETIVO: Avaliar a efetividade das estrategias de ensino utilizadas para o desenvolvimento do pensamento critico (PC) em estudantes de graduacao em Enfermagem. METODO: Revisao sistematica com metanalise baseada nas recomendacoes do Joanna Briggs Institute. A busca foi realizada nas bases de dados PubMed, CINAHL, EMBASE, Web of Science, SCOPUS, LILACS, Cochrane CENTRAL, PsycINFO e ERIC e de banco de teses dos quatro continentes. A selecao e avaliacao inicial dos estudos e a avaliacao da qualidade metodologica foi realizada por dois revisores de forma independente. RESULTADOS: Incluidos 12 ensaios clinico randomizados. Na metanalise, dos quatro estudos incluidos que avaliaram a estrategia do Problem Based Learning (PBL), comparada a palestras, foi demonstrada a efetividade do PBL, estatisticamente significativa (SMD=0,21 e 95% IC=0,01-0,42; p=0,0434) para o desenvolvimento do PC em estudantes de graduacao em Enfermagem e os estudos eram homogeneos (Qui quadrado=6,10, p=0,106). CONCLUSAO: Foi demonstrada a efetividade do PBL no aumento dos escores de PC global. Novos estudos precisam ser feitos com o objetivo de desenvolver, implementar e avaliar estrategias de ensino, que sejam pautadas em alto rigor metodologico e amparadas em modelos teoricos de ensino aprendizagem. PMID- 27384218 TI - Emergencies and acute diseases in the collected works of Hippocrates: observation, examination, prognosis, therapy. AB - The collected works omicronf Hippocrates include a wealth of references to emergencies and acute conditions; if the physician could treat these, he would be considered superior to his colleagues. Works most relevant to current Emergency Medicine are presented. They indicate Hippocrates' remarkable insight and attention to the value of close observation, meticulous clinical examination, and prognosis. Hippocrates and his followers disdained mystery and were not satisfied until they had discovered a rational cause to diseases. They assigned great significance to distressing signs and symptoms - the famous Hippocratic face, the breathing pattern, pain, seizures, opisthotonus - pointing to a fatal outcome, which they reported to their patient. The principles of treatment of emergencies, such as angina, haemorrhage, empyema, ileus, shoulder dislocations and head injuries, are astonishingly similar to the ones used nowadays. PMID- 27384220 TI - Environmental transmission of diarrheal pathogens in low and middle income countries. AB - Every year, more than half a million children die due to diarrheal diseases. Recent studies have identified the most important etiologies of diarrheal disease are enterotoxigenic and enteropathogenic E. coli, Shigella spp., rotavirus, norovirus and Cryptosporidium spp. These etiologies are unsurprisingly characterized by a combination of high shedding, high infectivity, and transmissibility through multiple environmental reservoirs. The relative importance of the transmission routes is likely site-specific. So the impact of interventions, which typically target only one or two environmental reservoirs, is likely also site-specific. The factors influencing the transmission routes most important for diarrheal disease are complex, including - at a minimum - etiology of endemic disease; and water, sanitation, and hygiene infrastructure and practices. The site-specific nature - and complexity of transmission - helps explain the observed variation in impacts of water, sanitation, and hygiene interventions. It may also render efforts to estimate or quantify global means for interventions' impacts irrelevant. The theme of this Perspective is that greater reductions in diarrheal disease transmission in LMICs can be achieved by designing interventions to interrupt the most important environmental transmission pathways. Intervention choice should be informed by site-specific conditions, most notably: diarrheal etiology and existing water, sanitation, and hygiene infrastructure and practices. The theme is discussed through the lens of the characteristics of the most important diarrheal diseases (shedding, infectivity, growth, and persistence) and the general characteristics of environmental reservoirs (exposure pathways and fecal contamination). The discussion highlights when interventions - and combinations of interventions - will be most effective at reducing diarrheal disease burden. PMID- 27384221 TI - An analysis of a humidifier disinfectant case from a toxicological perspective. AB - An analysis of patients and fatalities due to exposure to polyhexamethylene guanidine (PHMG) shows that PHMG causes mainly lung diseases such as pulmonary fibrosis. However, no research on the other organs has been conducted on this matter yet. So, an in-depth discussion on toxicological techniques is needed to determine whether or not PHMG is toxic to organs other than just the lungs. For the test of target organ toxicity by PHMG exposure, a toxicokinetic study must first be conducted. However, measurement method for PHMG injected into the body has not yet been established because it is not easy to analyze polymer PHMG, so related base studies on analytical technique for PHMG including radio-labeling chemistry must come first. Moreover, research on exposure-biomarker and effect biomarker must also be conducted, primarily related to clinical application. Several limitations seem to be expected to apply the biomarker study to the patient because much time has passed after exposure to the humidifier disinfectant. It is why a more comprehensive toxicological researches must be introduced to the causality for the victims. PMID- 27384222 TI - RhoB Acts as a Tumor Suppressor That Inhibits Malignancy of Clear Cell Renal Cell Carcinoma. AB - This study aims to investigate the biological role of RhoB in clear cell renal cell carcinoma (ccRCC). The expression of RhoB was examined in specimens of patients and cell lines by Western blot and Immunohistochemistry. The correlation between RhoB expression and clinicopathologic variables was also analyzed. The effects of RhoB on cell proliferation, cell cycle, cell apoptosis, and invasion/migration were detected by over-expression and knockdown of RhoB level in ccRCC cells via plasmids and RNAi. The results showed that RhoB was low expressed in ccRCC surgical specimens and cell lines compared with adjacent normal renal tissues and normal human renal proximal tubular epithelial cell lines (HKC), and its protein expression level was significantly associated with the tumor pathologic parameter embracing tumor size(P = 0.0157), pT stage(P = 0.0035), TNM stage(P = 0.0024) and Fuhrman tumor grade(P = 0.0008). Further, over expression of RhoB remarkably inhibited the cancer cell proliferation, colony formation and promoted cancer cell apoptosis, and aslo reduced the invasion and migration ability of ccRCC cells. Interestingly, up-regulation of RhoB could induce cell cycle arrest in G2/M phase and led to cell cycle regulators(CyclineB1,CDK1) and pro-apoptotic protein(casp3,casp9) aberrant expression. Moreover, knockdown of RhoB in HKC cells promoted cell proliferation and migration. Taken together, our study indicates that RhoB expression is decreased in ccRCC carcinogenesis and progression. Up-regulation of RhoB significantly inhibits ccRCC cell malignant phenotype. These findings show that RhoB may play a tumor suppressive role in ccRCC cells, raising its potential value in futural therapeutic target for the patients of ccRCC. PMID- 27384223 TI - Global alternans instability and its effect on non-linear wave propagation: dynamical Wenckebach block and self terminating spiral waves. AB - The main mechanism of formation of reentrant cardiac arrhythmias is via formation of waveblocks at heterogeneities of cardiac tissue. We report that heterogeneity and the area of waveblock can extend itself in space and can result formation of new additional sources, or termination of existing sources of arrhythmias. This effect is based on a new form of instability, which we coin as global alternans instability (GAI). GAI is closely related to the so-called (discordant) alternans instability, however its onset is determined by the global properties of the APD restitution curve and not by its slope. The APD-restitution curve relates the duration of the cardiac pulse (APD) to the time interval between the pulses, and can easily be measured in an experimental or even clinical setting. We formulate the conditions for the onset of GAI, study its manifestation in various 1D and 2D situations and discuss its importance for the onset of cardiac arrhythmias. PMID- 27384224 TI - Letter to Editor. PMID- 27384225 TI - Chemical Composition and Bioactivities of Two Common Chaenomeles Fruits in China: Chaenomeles speciosa and Chaenomeles sinensis. AB - Contents of total flavonoids, total phenolics, total triterpenes, total condensed tannin and total saponins in peels, flesh and endocarps of Chaenomeles speciosa (CSP) and Chaenomeles sinensis (CSS) were determined by colorimetric method, while 5 phenolics (vanillic, gallic, chlorogenic, ferulic and p-coumaric acids), 2 triterpenes (oleanolic and ursolic acids), and 3 flavonoids (rutin, catechin and epicatechin) were identified and quantified by high-performance liquid chromatography-mass spectrometry (HPLC-MS) and HPLC, and antioxidant and alpha glucosidase inhibitory activities of them also were evaluated as well as their digestive characteristics. In the correlation analysis, total phenolics, vanillic acid, catechin, ursolic acid and oleanolic acid all contribute to DPPH(.) scavenge capacity, gallic acid contributes to total ferric reducing antioxidant power, while total triterpenes, total saponins, chlorogenic acid and ferullic acid contribute to alpha-glucosidase inhibitory activity. In the principal component analysis, endocarps of CSP and CSS both show better quality than their peels and flesh, respectively. In vitro digestion can increase contents of total flavonoids, total condensed tannin and total saponins, while contents of total phenolics and total triterpenes decreased greatly. Our study would contribute to the full use of discarded parts of the 2 Chaenomeles and be helpful to establish a good foundation for further research of CSP and CSS. PMID- 27384226 TI - Water balance and irrigation water pumping of Lake Merdada for potato farming in Dieng Highland, Indonesia. AB - Lakes provide water resources for domestic use, livestock, irrigational use, etc. Water availability of lakes can be estimated using lake water balance. Lake water balance is calculated from the water input and output of a lake. Dieng Highland has several volcanic lakes in its surroundings. Lake Merdada in Dieng Highland has been experiencing extensive water pumping for several years more than other lakes in the surrounding area. It provides irrigation water for potato farming in Dieng Highland. The hydrological model of this lake has not been studied. The modeled water balance in this research uses primary data, i.e., bathymetric data, soil texture, and outflow discharge, as well as secondary data, i.e., rainfall, temperature, Landsat 7 ETM+ band 8 image, and land use. Water balance input components consist of precipitation on the surface area, surface (direct) runoff from the catchment area, and groundwater inflow and outflow (G net), while the output components consist of evaporation, river outflow, and irrigation. It shows that groundwater is the dominant input and output of the lake. On the other hand, the actual irrigation water pumping plays the leading role as human-induced alteration of outflow discharge. The maximum irrigation pumping modeling shows that it will decrease lake storage up to 37.14 % per month and may affect the ecosystem inside the lake. PMID- 27384227 TI - Environmental Status and geochemical assessment Sediments of Lake Skadar, Montenegro. AB - The environmental mobility and geochemical partitioning of ten metals were examined in sediments collected from the six locations around Lake Skadar in Montenegro. A three-step sequential extraction procedure was used to determine the distribution of the metals in various substrates of lacustrine sediments, and the concentrations were measured in the liquid extract by ICP-OES. The largest portion of the total amount of cadmium, strontium and manganese can be found in sediment bound to the hydrated iron and manganese oxides; cobalt, lead, copper and nickel in the oxidizable fraction and the highest portion of chromium, vanadium and zinc are in the residual fraction. The most mobilized and potentially mobile metals are strontium, cadmium and cobalt while the most immobilized metals are chromium, vanadium and zinc. Based on geochemical parameters, an assessment of sediment contamination by the investigated metals was performed and the results showed potential risks ranging from "no risk" to "low risk" to the environment. PMID- 27384228 TI - Herbicide and pesticide occurrence in the soils of children's playgrounds in Sarajevo, Bosnia and Herzegovina. AB - Pesticide pollution in Sarajevo public playgrounds is an important health and environmental issue, and the lack of information about it is causing concerns amongst the general population as well as researchers. Since children are in direct contact with surface soils on children's playgrounds, such soils should be much more carefully examined. Furthermore, herbicides and pesticides get transmitted from soil surfaces brought from outside the urban areas, or they get dispersed following their direct applications in urban areas. Infants' and children's health can be directly affected by polluted soils because of the inherent toxicity and widespread use of the different pesticides in urban environments such as playgrounds. In addition to that, the presence of chromated copper arsenate (CCA) wood preservative pesticide found as soil pollutant in playing equipment was also documented. Soil samples from playgrounds were collected and analyzed for triazines, carbamates, dithiocarbamates, phenolic herbicides and organochlorine pesticides. Samples for the determination of heavy metals Cu, Cr and As were prepared by microwave-assisted acid digestion, and the findings were determined by using an inductively coupled plasma optical emission spectrometer. Triazines, carbamates, dithiocarbamates, chlorphenoxy compounds, phenolic herbicides, organochlorine pesticides and organotin compounds were detected in playground soils and their determined concentrations (mg/kg) were respectively found as follows: <0.005, <0.05, <0.5, < 0.4, <0.1, <0.001 and <0.004. The determined contents (mg/kg) of Cu, Cr and As were in the ranges from 16.77 to 80.21, from 7.14 to 15.45 and from 3.31 to 4.43, respectively. Our preliminary results raise concerns about potential adverse effects of herbicides and pesticides on human health, which strengthens the case for a more preventative and protective approach to the uncontrolled presence of herbicides and pesticides in Sarajevo's playground soils. PMID- 27384229 TI - CRISPR: a versatile tool for both forward and reverse genetics research. AB - Human genetics research employs the two opposing approaches of forward and reverse genetics. While forward genetics identifies and links a mutation to an observed disease etiology, reverse genetics induces mutations in model organisms to study their role in disease. In most cases, causality for mutations identified by forward genetics is confirmed by reverse genetics through the development of genetically engineered animal models and an assessment of whether the model can recapitulate the disease. While many technological advances have helped improve these approaches, some gaps still remain. CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated), which has emerged as a revolutionary genetic engineering tool, holds great promise for closing such gaps. By combining the benefits of forward and reverse genetics, it has dramatically expedited human genetics research. We provide a perspective on the power of CRISPR-based forward and reverse genetics tools in human genetics and discuss its applications using some disease examples. PMID- 27384230 TI - Effects of arterial transit delay on cerebral blood flow quantification using arterial spin labeling in an elderly cohort. AB - PURPOSE: To investigate whether measurement of arterial transit time (ATT) can improve the accuracy of arterial spin labeling (ASL) cerebral blood flow (CBF) quantification in an elderly cohort due to the potentially prolonged ATT in the cohort. MATERIALS AND METHODS: We employed a 1-minute, low-resolution (12 mm in plane), sequential multidelay ATT measurement (both with and without vessel suppression) approach to characterize and correct ATT errors in CBF imaging of an elderly, clinical cohort. In all, 140 nondemented subjects greater than 70 years old were imaged at 3T with a single delay, volumetric continuous ASL sequence and also with the fast ATT measurement method. Nine healthy young subjects (28 +/- 6 years old) were also imaged. RESULTS: ATTs measured without vessel suppression (superior frontal: 1.51 +/- 0.27 sec) in the elderly were significantly shorter than those with suppression (P < 0.0001). Correction of CBF for ATT significantly increased average CBF in multiple brain regions where ATT was longer than the postlabeling delay (P < 0.01) and decreased intersubject variability of CBF in frontal, parietal, and occipital regions (P < 10-8 ). Measured ATT with vessel suppression was significantly longer in the elderly subjects (eg, superior frontal: 1.76 +/- 0.25 sec) compared to the younger adults (superior frontal: 1.59 +/- 0.19 sec) in basal ganglia and frontal cortical regions (P < 0.05). CONCLUSION: The ATT measurement is beneficial for imaging of elderly clinical populations. If ATT mapping is not feasible or available, postlabeling delays of 2-2.3 seconds should be used for elderly populations based on longest measured regional ATTs. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:472-481. PMID- 27384232 TI - Predictive validity of the ACC/AHA pooled cohort equations in predicting cancer specific mortality in a National Prospective Cohort Study of Adults in the United States. AB - BACKGROUND: The American College of Cardiology/American Heart Association Task Force on Practice Guidelines recently developed the Pooled Cohort Risk (PCR) equations to predict 10-years risk for a first atherosclerotic cardiovascular disease (ASCVD) event. The predictive validity of these PCR equations on cancer specific mortality among a national sample of US adults has yet to be evaluated, which was this study's purpose. METHODS: Data from the 1999-2010 National Health and Nutrition Examination Survey were used, with participants followed through December 31, 2011 to ascertain cancer mortality status via the National Death Index probabilistic algorithm. The analysed sample included 11,171 CVD-free adults (40-79 years). Ten-year risk of a first ASCVD was determined from the PCR equations. RESULTS: For the entire sample, 849,202 person-months occurred with an incidence rate of 0.31 cancer-specific deaths per 1,000 person-months. The unweighted follow-up duration was 72 months (IQR = 39-114). After adjusting for age, gender, race-ethnicity, physical activity and obesity, those with an elevated ASCVD (>= 7.5%) whom did not have a history of cancer at baseline had a 71% increased risk of cancer-specific mortality. There was less evidence for this relationship among those with a history of cancer. The individual components of the ASCVD that were predictive of cancer-specific mortality included age and smoking status. CONCLUSION: Ten-year predicted risk of a first ASCVD event via the PCR equations were significantly associated with cancer-specific mortality in a national sample of US adults (40-79 years) whom were free of cancer and CVD at baseline. In this American adult sample, the PCR equations provide evidence of predictive validity for cancer-specific mortality, particularly among those without cancer. PMID- 27384231 TI - Blood concentrations of carotenoids and retinol and lung cancer risk: an update of the WCRF-AICR systematic review of published prospective studies. AB - Carotenoids and retinol are considered biomarkers of fruits and vegetables intake, and are of much interest because of their anti-inflammatory and antioxidant properties; however, there is inconsistent evidence regarding their protective effects against lung cancer. We conducted a meta-analysis of prospective studies of blood concentrations of carotenoids and retinol, and lung cancer risk. We identified relevant prospective studies published up to December 2014 by searching the PubMed and several other databases. We calculated summary estimates of lung cancer risk for the highest compared with lowest carotenoid and retinol concentrations and dose-response meta-analyses using random effects models. We used fractional polynomial models to assess potential nonlinear relationships. Seventeen prospective studies (18 publications) including 3603 cases and 458,434 participants were included in the meta-analysis. Blood concentrations of alpha-carotene, beta-carotene, total carotenoids, and retinol were significantly inversely associated with lung cancer risk or mortality. The summary relative risk were 0.66 (95% confidence interval [CI]: 0.55-0.80) per 5 MUg/100 mL of alpha-carotene (studies [n] = 5), 0.84 (95% CI: 0.76-0.94) per 20 MUg/100 mL of beta-carotene (n = 9), 0.66 (95% CI: 0.54-0.81) per 100 MUg/100 mL of total carotenoids (n = 4), and 0.81 (95% CI: 0.73-0.90) per 70 MUg/100 mL of retinol (n = 8). In stratified analysis by sex, the significant inverse associations for beta-carotene and retinol were observed only in men and not in women. Nonlinear associations were observed for beta-carotene, beta cryptoxanthin, and lycopene, with stronger associations observed at lower concentrations. There were not enough data to conduct stratified analyses by smoking. In conclusion, higher blood concentrations of several carotenoids and retinol are associated with reduced lung cancer risk. Further studies in never and former smokers are needed to rule out confounding by smoking. PMID- 27384233 TI - Precise protein assembly of array structures. AB - The assembly of proteins into various nano-objects with regular and periodic microstructures, i.e. protein arrays, is a fast-growing field in materials science. Due to the structural complexity of proteins, reports in this field are still quite limited. In this review, we summarize the recent developments in protein array construction by different driving forces, including electrostatic interactions, metal-ligand interactions, molecular recognition and protein protein interactions. In line with our particular interest, assemblies driven by molecular recognition are particularly explored. Finally, functionalities of the obtained protein arrays are briefly discussed. PMID- 27384234 TI - Our endless search for a scientific paradigm is not over. PMID- 27384235 TI - Cancer Drug Pricing and Reimbursement: Lessons for the United States From Around the World. PMID- 27384236 TI - When the Patient Says No. PMID- 27384238 TI - The modelling of odour dispersion as a support tool for the improvements of high odours impact plants. AB - Two scenarios in terms of odour impact assessment were studied during the phase of upgrading of an existing waste treatment plant: CALPUFF was used for the simulation of odour dispersion. Olfactometric measures, carried out over different periods and different positions in the plant, were used for model calibration. Results from simulations were reported in terms of statistics of odour concentrations and isopleths maps of the 98th percentile of the hourly peak concentrations, as requested from the European legislation and standards. The excess perception thresholds and emissions were utilized to address the plant upgrade options. The hourly evaluation of odours was performed to determine the most impacting period of the day. An inverse application of the numerical simulation starting from defining the odour threshold at the receptor was made to allow the definition of the required abatement efficiency at the odours source location. Results from the proposed approach confirmed the likelihood to adopt odour dispersion modelling, not only in the authorization phase, but also as a tool for driving technical and managing actions in plant upgrade so to reduce impacts and improve the public acceptance. The upgrade actions in order to achieve the expected efficiency are reported as well. PMID- 27384239 TI - Secure Scientific Applications Scheduling Technique for Cloud Computing Environment Using Global League Championship Algorithm. AB - Cloud computing system is a huge cluster of interconnected servers residing in a datacenter and dynamically provisioned to clients on-demand via a front-end interface. Scientific applications scheduling in the cloud computing environment is identified as NP-hard problem due to the dynamic nature of heterogeneous resources. Recently, a number of metaheuristics optimization schemes have been applied to address the challenges of applications scheduling in the cloud system, without much emphasis on the issue of secure global scheduling. In this paper, scientific applications scheduling techniques using the Global League Championship Algorithm (GBLCA) optimization technique is first presented for global task scheduling in the cloud environment. The experiment is carried out using CloudSim simulator. The experimental results show that, the proposed GBLCA technique produced remarkable performance improvement rate on the makespan that ranges between 14.44% to 46.41%. It also shows significant reduction in the time taken to securely schedule applications as parametrically measured in terms of the response time. In view of the experimental results, the proposed technique provides better-quality scheduling solution that is suitable for scientific applications task execution in the Cloud Computing environment than the MinMin, MaxMin, Genetic Algorithm (GA) and Ant Colony Optimization (ACO) scheduling techniques. PMID- 27384237 TI - Deciphering and Targeting Oncogenic Mutations and Pathways in Breast Cancer. AB - : Advances in DNA and RNA sequencing revealed substantially greater genomic complexity in breast cancer than simple models of a few driver mutations would suggest. Only very few, recurrent mutations or copy-number variations in cancer causing genes have been identified. The two most common alterations in breast cancer are TP53 (affecting the majority of triple-negative breast cancers) and PIK3CA (affecting almost half of estrogen receptor-positive cancers) mutations, followed by a long tail of individually rare mutations affecting <1%-20% of cases. Each cancer harbors from a few dozen to a few hundred potentially high functional impact somatic variants, along with a much larger number of potentially high-functional impact germline variants. It is likely that it is the combined effect of all genomic variations that drives the clinical behavior of a given cancer. Furthermore, entirely new classes of oncogenic events are being discovered in the noncoding areas of the genome and in noncoding RNA species driven by errors in RNA editing. In light of this complexity, it is not unexpected that, with the exception of HER2 amplification, no robust molecular predictors of benefit from targeted therapies have been identified. In this review, we summarize the current genomic portrait of breast cancer, focusing on genetic aberrations that are actively being targeted with investigational drugs. IMPLICATIONS FOR PRACTICE: Next-generation sequencing is now widely available in the clinic, but interpretation of the results is challenging, and its impact on treatment selection is often limited. This work provides an overview of frequently encountered molecular abnormalities in breast cancer and discusses their potential therapeutic implications. This review emphasizes the importance of administering investigational targeted therapies, or off-label use of approved targeted drugs, in the context of a formal clinical trial or registry programs to facilitate learning about the clinical utility of tumor target profiling. PMID- 27384240 TI - Isoelectronic Tungsten Doping in Monolayer MoSe2 for Carrier Type Modulation. AB - Carrier-type modulation is demonstrated in 2D transition metal dichalcogenides as n-type monolayer MoSe2 is converted to nondegenerate p-type monolayer Mo1-x Wx Se2 through isoelectronic doping. Although the alloys are mesoscopically uniform, the p-type conduction in monolayer Mo1-x Wx Se2 appears to originate from the upshift of the valenceband maximum toward the Fermi level at highly localized "W rich" regions in the lattice. PMID- 27384241 TI - Incremental cancer detection using breast ultrasonography versus breast magnetic resonance imaging in the evaluation of newly diagnosed breast cancer patients. AB - OBJECTIVE: To compare the incremental cancer detection rate (ICDR) using bilateral whole-breast ultrasonography (BWBUS) vs dynamic contrast-enhanced MRI in patients with primary breast cancer. METHODS: A retrospective database search in a single institution identified 259 patients with breast cancer diagnosed from January 2011 to August 2014 who underwent mammography, BWBUS and MRI before surgery. Patient characteristics, tumour characteristics and lesions seen on each imaging modality were recorded. The sensitivity, specificity and accuracy for each modality were calculated. ICDRs according to index tumour histology and receptor status were also evaluated. The effect of additional cancer detection on surgical planning was obtained from the medical records. RESULTS: A total of 266 additional lesions beyond 273 index malignancies were seen on at least 1 modality, of which 121 (45%) lesions were malignant and 145 (55%) lesions were benign. MRI was significantly more sensitive than BWBUS (p = 0.01), while BWBUS was significantly more accurate and specific than MRI (p < 0.0001). Compared with mammography, the ICDRs using BWBUS and MRI were significantly higher for oestrogen receptor-positive and triple-negative cancers, but not for human epidermal growth factor receptor 2-positive cancers. 22 additional malignant lesions in 18 patients were seen on MRI only. Surgical planning remained unchanged in 8 (44%) of those 18 patients. CONCLUSION: MRI was more sensitive than BWBUS, while BWBUS was more accurate and specific than MRI. MRI-detected additional malignant lesions did not change surgical planning in almost half of these patients. ADVANCES IN KNOWLEDGE: BWBUS may be a cost-effective and practical tool in breast cancer staging. PMID- 27384242 TI - The intensive care infection score - a novel marker for the prediction of infection and its severity. AB - BACKGROUND: The prediction of infection and its severity remains difficult in the critically ill. A novel, simple biomarker derived from five blood-cell derived parameters that characterize the innate immune response in routine blood samples, the intensive care infection score (ICIS), could be helpful in this respect. We therefore compared the predictive value of the ICIS with that of the white blood cell count (WBC), C-reactive protein (CRP) and procalcitonin (PCT) for infection and its severity in critically ill patients. METHODS: We performed a multicenter, cluster-randomized, crossover study in critically ill patients between January 2013 and September 2014. Patients with a suspected infection for which blood cultures were taken by the attending intensivist were included. Blood was taken at the same time for WBC, ICIS, CRP and PCT measurements in the control study periods. Results of imaging and cultures were collected. Patients were divided into groups of increasing likelihood of infection and invasiveness: group 1 without infection or with possible infection irrespective of cultures, group 2 with probable or microbiologically proven local infection without blood stream infection (BSI) and group 3 with BSI irrespective of local infection. Septic shock was assessed. RESULTS: In total, 301 patients were enrolled. CRP, PCT and ICIS were higher in groups 2 and 3 than group 1. The area under the receiver operating characteristic curve (AUROC) for the prediction of infection was 0.70 for CRP, 0.71 for PCT and 0.73 for ICIS (P < 0.001). For the prediction of septic shock the AUROC was 0.73 for CRP, 0.85 for PCT and 0.76 for ICIS. These AUROC did not differ from each other. CONCLUSION: The data suggest that the ICIS is potentially useful for the prediction of infection and its severity in critically ill patients, non-inferiorly to CRP and PCT. In contrast to CRP and PCT, the ICIS can be determined routinely without extra blood sampling and lower costs, yielding results within 15 minutes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ID NCT01847079 . Registered on 24 April 2013. PMID- 27384244 TI - Operator dermal exposure and protection provided by personal protective equipment and working coveralls during mixing/loading, application and sprayer cleaning in vineyards. AB - The efficiency of a working coverall combined with personal protective equipment to protect operators against dermal exposure to plant protection products under field conditions was studied. Operators wore a non-certified water-repellent finish polyester/cotton coverall plus a certified gown during the mixing/loading and the cleaning phases. Insecticide foliar application to a vineyard was selected as the exposure scenario. The overall dermal residue levels measured in this study were in the range of data recently collected in Europe. The water repellent finish working coverall reduced body exposure by a factor of approximately 95%. Wearing a Category III Type 3 partial body gown during mixing/loading and cleaning of the application equipment led to a further protective effect of 98.7%. The combination of a water-repellent finish working coverall and partial body protection during specific tasks provided satisfactory levels of protection and can be considered as suitable protection for the conditions of use studied. PMID- 27384243 TI - Conditional ablation of myeloid TNF increases lesion volume after experimental stroke in mice, possibly via altered ERK1/2 signaling. AB - Microglia are activated following cerebral ischemia and increase their production of the neuro- and immunomodulatory cytokine tumor necrosis factor (TNF). To address the function of TNF from this cellular source in focal cerebral ischemia we used TNF conditional knock out mice (LysMcreTNF(fl/fl)) in which the TNF gene was deleted in cells of the myeloid lineage, including microglia. The deletion reduced secreted TNF levels in lipopolysaccharide-stimulated cultured primary microglia by ~93%. Furthermore, phosphorylated-ERK/ERK ratios were significantly decreased in naive LysMcreTNF(fl/fl) mice demonstrating altered ERK signal transduction. Micro-PET using (18)[F]-fluorodeoxyglucose immediately after focal cerebral ischemia showed increased glucose uptake in LysMcreTNF(fl/fl) mice, representing significant metabolic changes, that translated into increased infarct volumes at 24 hours and 5 days compared to littermates (TNFfl/fl). In naive LysMcreTNF(fl/fl) mice cytokine levels were low and comparable to littermates. At 6 hours, TNF producing microglia were reduced by 56% in the ischemic cortex in LysMcreTNF(fl/fl) mice compared to littermate mice, whereas no TNF(+) leukocytes were detected. At 24 hours, pro-inflammatory cytokine (TNF, IL 1beta, IL-6, IL-5 and CXCL1) levels were significantly lower in LysMcreTNF(fl/fl) mice, despite comparable infiltrating leukocyte populations. Our results identify microglial TNF as beneficial and neuroprotective in the acute phase and as a modulator of neuroinflammation at later time points after experimental ischemia, which may contribute to regenerative recovery. PMID- 27384245 TI - Sustained versus intermittent lung inflation for resuscitation of preterm infants: a randomized controlled trial. AB - AIM: To evaluate efficacy and safety of delivery room (DR) sustained lung inflation (SLI) in resuscitation of preterm neonates. METHODS: Randomized Controlled Trial including 112 preterm infants randomized to either SLI (n = 57) using T-piece resuscitator [maximum three inflations with maximum pressure of 30 cmH2O for 15 s followed by continuous positive airway pressure (CPAP) of 5-7 cmH2O] or conventional bag/mask inflation (CBMI) (n = 55) using traditional self inflating bag (maximum pressure of 40 cmH2O at a rate of 40-60 per min). Failure was defined as the need for DR or first 72 h intubation. Cord and 2-h post resuscitation blood samples were collected to measure interleukin (IL)-1beta and tumor necrosis factor-alpha levels before and after intervention. RESULTS: SLI was associated with significantly higher success rate compared to CBMI [75.4 versus 54.5%; p = 0.017], lower need for DR intubation [5.3% versus 23.6%; (X2 = 7.7; p = 0.005)], higher 5-min-Apgar score (median 8 versus 7; p = 0.018), shorter duration on nasal-CPAP (p = 0.017), and non-significantly different air leak (7% versus 11%; p = 0.3) and bronchopulmonary dysplasia rates among survivors (2% versus 11%; p = 0.09). Post-resuscitation IL-1beta plasma levels increased significantly in CBMI (p = 0.009) and not in SLI group. CONCLUSION: Delivery room SLI is more effective than intermittent bag and mask inflation for improving short-term respiratory outcome in preterm infants, without significant adverse effects. PMID- 27384247 TI - The Effect of Solvation on the Radiation Damage Rate Constants for Adenine. AB - It is well known that water plays an important part in almost all biological systems and that inclusion of solvation effects might therefore be of utmost importance in studies of radiation damage to DNA. In the present investigation, we have studied the effect of different solvation models in calculations of Gibbs free energies and reaction rates for the reaction between the OH radical and the DNA nucleobase adenine by conducting density functional theory calculations at the omegaB97X-D/6-311++G(2df,2pd) level with the Eckart tunnelling correction. The solvent, water, was included through either the implicit polarizable continuum model (PCM) or through explicit modelling of micro-solvation by a single water molecule at the site of reaction as well as by the combination of both. Scrutiny of the thermodynamics and kinetics of the individual sub-reactions suggests that the qualitative differences introduced by the solvation models do not significantly alter the conclusions made based solely on simple gas-phase calculations. Abstraction of the amine hydrogen atoms H61 and H62 and addition onto C8 remain the most likely reaction pathways. PMID- 27384248 TI - In Silico Calculation of Infinite Dilution Activity Coefficients of Molecular Solutes in Ionic Liquids: Critical Review of Current Methods and New Models Based on Three Machine Learning Algorithms. AB - The aim of the paper is to address all the disadvantages of currently available models for calculating infinite dilution activity coefficients (gamma(infinity)) of molecular solutes in ionic liquids (ILs)-a relevant property from the point of view of many applications of ILs, particularly in separations. Three new models are proposed, each of them based on distinct machine learning algorithm: stepwise multiple linear regression (SWMLR), feed-forward artificial neural network (FFANN), and least-squares support vector machine (LSSVM). The models were established based on the most comprehensive gamma(infinity) data bank reported so far (>34 000 data points for 188 ILs and 128 solutes). Following the paper published previously [J. Chem. Inf. Model 2014, 54, 1311-1324], the ILs were treated in terms of group contributions, whereas the Abraham solvation parameters were used to quantify an impact of solute structure. Temperature is also included in the input data of the models so that they can be utilized to obtain temperature-dependent data and thus related thermodynamic functions. Both internal and external validation techniques were applied to assess the statistical significance and explanatory power of the final correlations. A comparative study of the overall performance of the investigated SWMLR/FFANN/LSSVM approaches is presented in terms of root-mean-square error and average absolute relative deviation between calculated and experimental gamma(infinity), evaluated for different families of ILs and solutes, as well as between calculated and experimental infinite dilution selectivity for separation problems benzene from n-hexane and thiophene from n-heptane. LSSVM is shown to be a method with the lowest values of both training and generalization errors. It is finally demonstrated that the established models exhibit an improved accuracy compared to the state-of-the-art model, namely, temperature-dependent group contribution linear solvation energy relationship, published in 2011 [J. Chem. Eng. Data 2011, 56, 3598-3606]. PMID- 27384249 TI - New insights into Cdk2 regulation during meiosis. PMID- 27384250 TI - Porous Molybdenum Phosphide Nano-Octahedrons Derived from Confined Phosphorization in UIO-66 for Efficient Hydrogen Evolution. AB - Herein, a series of porous nano-structured carbocatalysts have been fused and decorated by Mo-based composites, such as Mo2 C, MoN, and MoP, to form a hybrid structures. Using the open porosity derived from the pyrolysis of metal-organic frameworks (MOFs), the highly dispersive MoO2 small nanoparticles can be deposited in porous carbon by chemical vapor deposition (CVD). Undergoing different treatments of carbonization, nitridation, and phosphorization, the Mo2 C-, MoN-, and MoP-decorated carbocatalysts can be selectively prepared with un changed morphology. Among these Mo-based composites, the MoP@Porous carbon (MoP@PC) composites exhibited remarkable catalytic activity for the hydrogen evolution reaction (HER) in 0.5 m H2 SO4 aqueous solution versus MoO2 @PC, Mo2 C@PC, and MoN@PC. This study gives a promising family of multifunctional lab-on-a particle architectures which shed light on energy conversion and fuel-cell catalysis. PMID- 27384251 TI - The influence of thoughts of death and suicidal ideation on the course of depression in older depressed patients. AB - OBJECTIVE: Thoughts of death are not regularly included in diagnostic instruments and rarely examined separately from thoughts of suicide. This exploratory study examined whether thoughts of death and thoughts of suicide affect the course of late-life depressive disorders. METHODS: In 378 depressed older persons, thoughts of death and thoughts of suicide were assessed using questions from the Composite International Diagnostic Interview. After 2 years, the presence of a DSM-IV-TR diagnosis of minor or major depression or dysthymia was assessed with the Composite International Diagnostic Interview. The Inventory of Depressive Symptomatology was administered every 6 months up till 3-year follow-up. RESULTS: Multinomial logistic regression showed that thoughts of death as well as thoughts of suicide predicted double depression at follow-up (OR = 2.14 [95% CI: 1.04 4.40] and OR = 6.47 [95% CI: 2.22-3.02], respectively), compared with patients without these thoughts. Results became non-significant when adjusted for baseline depression severity (OR = 1.17 [95% CI: 0.52-2.63] and OR = 2.57 [95% CI: 0.79 8.84], respectively). Mixed linear models showed that severity of depression was lowest in the reference group, while symptoms decreased more over time in those with either thoughts of death or suicide. CONCLUSIONS: Patients with thoughts of death or with thoughts of suicide were more severely depressed at baseline and follow-up, with the highest risk of being depressed at follow-up for patients with thoughts of suicide. These associations could be explained by baseline depression severity. The results suggest that thoughts of death and thoughts of suicide are important risk markers in predicting the course of depression. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27384252 TI - Vascular Access Tracking System: a Web-Based Clinical Tracking Tool for Identifying Catheter Related Blood Stream Infections in Interventional Radiology Placed Central Venous Catheters. AB - Vascular access is invaluable in the treatment of hospitalized patients. Central venous catheters provide a durable and long-term solution while saving patients from repeated needle sticks for peripheral IVs and blood draws. The initial catheter placement procedure and long-term catheter usage place patients at risk for infection. The goal of this project was to develop a system to track and evaluate central line-associated blood stream infections related to interventional radiology placement of central venous catheters. A customized web based clinical database was developed via open-source tools to provide a dashboard for data mining and analysis of the catheter placement and infection information. Preliminary results were gathered over a 4-month period confirming the utility of the system. The tools and methodology employed to develop the vascular access tracking system could be easily tailored to other clinical scenarios to assist in quality control and improvement programs. PMID- 27384253 TI - Point-of-care PT and aPTT in patients with suspected deficiencies of coagulation factors. AB - INTRODUCTION: There are several clinical settings and patient conditions especially in intensive care units, emergency departments, and operating theaters, where the coagulation status of a patient must be known immediately and point-of-care (POC) systems are beneficial due to low time to result. METHODS: This noninterventional, single-blinded, multicenter study with prospectively collected whole blood samples was performed to evaluate the diagnostic accuracy of the CoaguChek PT Test (POC PT) and CoaguChek aPTT Test (POC aPTT) compared to standard laboratory testing in patients with suspected deficiencies of coagulation factors. RESULTS: In total, 390 subjects were included. Both POC PT and POC aPTT showed concordance with the laboratory PT and aPTT. Lot-to-lot variation was below 2% both for POC PT and for POC aPTT. The mean relative difference of capillary blood compared to venous blood was 0.2 % with POC PT and 8.4% with POC aPTT. The coefficients of variation for repeatability of POC PT using whole blood were found to be between 2% and 3.6%. CONCLUSION: Our findings suggest reliable quantitative results with this POC system to support on-site decision-making for patients with suspected deficiencies of coagulation factors in acute and intensive care. PMID- 27384254 TI - Nano-structured gemini-based supramolecular solvent for the microextraction of cyhalothrin and fenvalerate. AB - A novel supramolecular solvent-based microextraction followed by high-performance liquid chromatography with ultraviolet detection method has been developed for the extraction and determination of two pyrethroid analytes, cyhalothrin and fenvalerate, in water and soil samples. The liquid-liquid-phase separation of surfactants has been used in analytical extraction. The surfactant-rich phase is a nano-structured liquid, recently named as a supramolecular solvent, generated from the amphiphiles. The alkyl carboxylic acid based supramolecular solvents were introduced before. Coacervates made up of gemini surfactant, consisting of two amphiphilic moieties, were first used as solvent. The effective parameters on extraction (i.e., type of organic solvent, the amount of surfactant and volume of tetrahydrofuran, sample solution pH, salt addition, ultrasonic and centrifugation time) were investigated and optimized. Under the optimum conditions, preconcentration factors of 110 and 145 were obtained for the analytes. The linearity was 0.5-200.0 MUg/L with the correlation of determination of (R(2) ) >= 0.9984. The limit of detection of the method was (S/N = 3) 0.2 MUg/L, and precisions in the range of 6.3-10.3% (RSDs, n = 5) were obtained. This method has been successfully applied to analyze real samples, and good recoveries in the range of 101.2-108.8% were obtained. PMID- 27384255 TI - Dual-Sensitive Charge-Conversional Polymeric Prodrug for Efficient Codelivery of Demethylcantharidin and Doxorubicin. AB - A tumor is a complicated system, and tumor cells are typically heterogeneous in many aspects. Polymeric drug delivery nanocarriers sensitive to a single type of biosignals may not release cargos effectively in all tumor cells, leading to low therapeutic efficacy. To address the challenges, here, we demonstrated a pH/reduction dual-sensitive charge-conversional polymeric prodrug strategy for efficient codelivery. Reduction-sensitive disulfide group and acid-labile anticancer drug (demethylcantharidin, DMC)-conjugated beta-carboxylic amide group were repeatedly and regularly introduced into copolymer chain simultaneously via facile CuAAC click polymerization. The obtained multifunctional polymeric prodrug P(DMC), mPEG-b-poly(disulfide-alt-demethylcantharidin)-b-mPEG was further utilized for DOX encapsulation. Under tumor tissue/cell microenvironments (pH 6.5 and 10 mM GSH), the DOX-loaded polymeric prodrug nanoparticles (P(DMC)@DOX NPs) performed surface negative-to-positive charge conversion and accelerated/sufficient release of DMC and DOX. The remarkably enhanced cellular internalization and cytotoxicity in vitro, especially against DOX-resistant SMMC 7721 cells, were demonstrated. P(DMC)@DOX NPs in vivo also exhibited higher tumor accumulation and improved antitumor efficiency compared to P(SA)@DOX NPs with one drug and without charge-conversion ability. The desired multifunctional polymeric prodrug strategy brings a new opportunity for cancer chemotherapy. PMID- 27384256 TI - Sloughing esophagitis: a spectacular histologic and endoscopic disease without a uniform clinical correlation. AB - Sloughing esophagitis, also currently known as esophagitis dissecans superficialis, is a degenerative disease of the squamous epithelium characterized by superficial epithelial necrosis with parakeratosis, but without inflammation, and detachment of the superficial necrotic zone from the deep viable zone. This leads to a spectacular endoscopic appearance of sloughed mucosa in streaks and patches. The cause is unknown, and the clinical characteristics are variable, ranging from incidentally findings to esophageal symptoms. The disease seems to be self-limited, as resolution of the changes was observed in the few cases for which follow-up endoscopic examinations have been reported. PMID- 27384257 TI - Dielectrophoretic sphere-wall repulsion due to a uniform electric field. AB - When a zero-net-charge particle is placed under a uniform electric field, the decay of the Maxwell stress with the third power of distance ensures a nil electric force. A nonzero force may nonetheless be generated in the presence of a planar wall due to a mechanism which resembles conventional dielectrophoresis under nonuniform fields. In the prototypical case of a spherical particle this force acts perpendicular to the wall; its magnitude depends upon the pertinent boundary conditions governing the electric potential. When a particle is suspended in an electrolyte solution, where the double-layer structure ensures zero net charge, these conditions are electrokinetic in nature; they involve a balance between bulk conduction and diffusion, represented by normal derivatives, and an effective surface-conduction mechanism, represented by surface-Laplacian terms whose magnitude is quantified by appropriate Dukhin numbers. The dimensionless force depends upon the particle and wall Dukhin numbers as well as the ratio lambda of the size of the particle to its distance from the wall. The remote-particle limit lambda ? 1 is addressed using successive reflections. Calculation of the first few terms in the asymptotic expansion of the force only requires the evaluation of a single reflection from the wall. The leading-order term, scaling as lambda(4), is repulsive, with a magnitude that varies non monotonically with the particle Dukhin number and is independent of the wall Dukhin number. Surface conditions on the wall enter only at the O(lambda(5)) leading-order correction. PMID- 27384258 TI - New Pyridinium Ylide Dyes for Dye Sensitized Solar Cell Applications. AB - Novel organic pyridinium ylide sensitizers (NO109-111) consisting of various anchoring groups were synthesized and characterized for applications in dye sensitized solar cells. Compared with the pyridine-N-oxide dye (NO108), the ylide sensitizers with strong electron-withdrawing acceptors exhibited dominant ultraviolet absorption properties and efficient binding abilities to the TiO2 surface. Among these dyes, the pyridinium ylide NO111 sensitized solar cell showed the highest efficiency (5.15%), which was improved to 7.41% by employing coadsorbent chenodeoxycholic acid. PMID- 27384259 TI - Development of Enantiospecific Coupling of Secondary and Tertiary Boronic Esters with Aromatic Compounds. AB - The stereospecific cross-coupling of secondary boronic esters with sp(2) electrophiles (Suzuki-Miyaura reaction) is a long-standing problem in synthesis, but progress has been achieved in specific cases using palladium catalysis. However, related couplings with tertiary boronic esters are not currently achievable. To address this general problem, we have focused on an alternative method exploiting the reactivity of a boronate complex formed between an aryl lithium and a boronic ester. We reasoned that subsequent addition of an oxidant or an electrophile would remove an electron from the aromatic ring or react in a Friedel-Crafts-type manner, respectively, generating a cationic species, which would trigger 1,2-migration of the boron substituent, creating the new C-C bond. Elimination (preceded by further oxidation in the former case) would result in rearomatization giving the coupled product stereospecifically. Initial work was examined with 2-furyllithium. Although the oxidants tested were unsuccessful, electrophiles, particularly NBS, enabled the coupling reaction to occur in good yield with a broad range of secondary and tertiary boronic esters, bearing different steric demands and functional groups (esters, azides, nitriles, alcohols, and ethers). The reaction also worked well with other electron-rich heteroaromatics and 6-membered ring aromatics provided they had donor groups in the meta position. Conditions were also found under which the B(pin)- moiety could be retained in the product, ortho to the boron substituent. This protocol, which created a new C(sp(2))-C(sp(3)) and an adjacent C-B bond, was again applicable to a range of secondary and tertiary boronic esters. In all cases, the coupling reaction occurred with complete stereospecificity. Computational studies verified the competing processes involved and were in close agreement with the experimental observations. PMID- 27384260 TI - Metabolomic Analysis of Gastric Cancer Progression within the Correa's Cascade Using Ultraperformance Liquid Chromatography-Mass Spectrometry. AB - Gastric cancer (GC) is among the most common cancers worldwide. Gastric carcinogenesis is a multistep and multifactorial process beginning with chronic gastritis induced by Helicobacter pylori (H. pylori) infection. This process is often described via a sequence of events known as Correas's cascade, a stepwise progression from nonactive gastritis, chronic active gastritis, precursor lesions of gastric cancer (atrophy, intestinal metaplasia, and dysplasia), and finally adenocarcinoma. Our aim was to identify a plasma metabolic pattern characteristic of GC through disease progression within the Correa's cascade. This study involved the analysis of plasma samples collected from 143 patients classified in four groups: patients with nonactive gastritis and no H. pylori infection, H. pylori infected patients with chronic active gastritis, infected or noninfected patients with precursor lesions of gastric cancer, and GC. Independent partial least-squares-discriminant binary models of UPLC-ESI(+)-TOFMS metabolic profiles, implemented in a decision-directed acyclic graph, allowed the identification of tryptophan and kynurenine as discriminant metabolites that could be attributed to indoleamine-2,3-dioxygenase upregulation in cancer patients leading to tryptophan depletion and kynurenine metabolites generation. Furthermore, phenylacetylglutamine was also classified as a discriminant metabolite. Our data suggest the use of tryptophan, kynurenine, and phenylacetylglutamine as potential GC biomarkers. PMID- 27384261 TI - Natural Products as Mechanism-based Anticancer Agents: Sp Transcription Factors as Targets. AB - Naturally occurring anticancer agents and their derivatives act on multiple pathways to inhibit carcinogenesis and their inhibition of migration, invasion, growth, survival, and metastasis is associated with downregulation of genes associated with these responses. Several phytochemical-derived anticancer drugs including curcumin, betulinic acid, phenethylisothiocyanate and celastrol, and many others induce reactive oxygen species, and their effects on gene regulation show some overlap in various cancer cell lines. We hypothesize that reactive oxygen species-inducing anticancer agents and many other natural products target a common pathway in cancer cells, which initially involves downregulation of specificity protein 1 (Sp1), Sp3, and Sp4, which are highly expressed in tumors/cell lines derived from solid tumors. This hypothesis is supported by several published reports showing that a large number of phytochemical-derived anticancer agents downregulate Sp1, Sp3, Sp4, and pro-oncogenic Sp-regulated genes involved in cell growth (cyclin D1 and growth factor receptors), survival (bcl-2 and survivin), angiogenesis and migration (MMP-9, vascular endothelial growth factor and its receptors), and inflammation (NF-kB). The contribution of this pathway to the anticancer activity of drugs such as curcumin, celastrol, betulinic acid, and phenethylisothiocyanate must be determined in order to optimize clinical applications of drug combinations containing these compounds. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27384262 TI - Co-existence of Intravascular Papillary Endothelial Hyperplasia in Superficial Skin and the Intermuscular Space. PMID- 27384263 TI - Pd-catalyzed divergent trifluoroethylation and arylation of arylboronic acids by aryl(2,2,2-trifluoroethyl)iodonium triflates. AB - Highly electrophilic aryl(2,2,2-trifluoroethyl)iodonium triflates have been used for the first time as trifluoroethyl and aryl transfer reagents in Pd-catalyzed functionalization of arylboronic acids. Electron-rich arylboronic acids reacted with aryl(2,2,2-trifluoroethyl)iodonium triflates (2a-b) in CH3CN in the presence of Pd2(dba)3 and K3PO4 at room temperature to provide trifluoroethyl arenes in up to 82% yield, while the reactions of both electron-rich and -poor arylboronic acids with 2a-b in DMF in the presence of Pd[P(t-Bu)3]2 and Cs2CO3 at 40 degrees C afforded arylation products in up to 99% yield. This tunable protocol allows access to trifluoroethyl arenes or biaryls in good to excellent yields under mild conditions and without the addition of extra ligands. PMID- 27384264 TI - Control of anticoagulation with vitamin K antagonists: overestimation of median time in therapeutic range when assessed by linear interpolation. AB - Patients receiving vitamin K-antagonists are monitored by regular assessment of the International Normalized Ratio (INR). There are two popular methods for therapeutic control of anticoagulation in patient groups: 1) Time in Therapeutic Range (TTR) assessed by linear interpolation of successive INR measurements; 2) the cross-sectional proportion (CSP) of all patients' last INRs within range. The purpose of the present study is to compare the two methods using data from 53 Dutch Thrombosis Centres and to develop a semi-quantitative model for TTR based on different types of INR change. Different groups of around 400,000 patients in four consecutive years were evaluated: patients in the induction phase, short term, long-term, low-target range, high-target range, receiving either acenocoumarol or phenprocoumon, and performing self-management. Each Centre provided TTR and CSP results for each patient group. TTR and CSP were compared using the Wilcoxon signed-rank test. Separately, we analysed the relationship between consecutive INR results regarding in or out of range and their frequency of occurrence in patients of two different cohorts. Good correlation was observed between TTR and CSP (correlation coefficient 0.694-0.950 in low-target range). In long-term acenocoumarol patients (low-target range) the median TTR was significantly higher than CSP (80.0 % and 78.7 %, respectively; p<0.001). In long term phenprocoumon patients (low-target range) there was no significant difference between median TTR (83.0 %) and median CSP (82.6 %). In conclusion, the correlation between TTR assessed by linear interpolation and CSP was good. TTR assessed by linear interpolation was higher than CSP in patients on acenocoumarol. PMID- 27384265 TI - In utero exposure to venlafaxine, a serotonin-norepinephrine reuptake inhibitor, increases cardiac anomalies and alters placental and heart serotonin signaling in the rat. AB - BACKGROUND: Human studies are inconsistent with respect to an association between treatment with selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRI/SNRIs) and an increase in the incidence of congenital heart defects. Here we tested the hypothesis that in utero exposure to venlafaxine, a highly prescribed SNRI, increases the incidence of fetal heart defects and alters placental and fetal heart serotonin signaling in the rat. METHODS: Timed-pregnant Sprague Dawley rats were gavaged daily with venlafaxine hydrochloride (0, 3, 10, 30, or 100 mg/kg/day) from gestation day 8 to 20. On gestation day 21, fetuses were examined for external and internal malformations; placentas and fetal hearts were collected for the analysis of gene expression. RESULTS: Venlafaxine had no effect on the number of live fetuses, fetal body weights, or external morphology in the absence of maternal toxicity. However, venlafaxine significantly increased the placental index (fetal body/placental weight ratio) and the incidence of fetal cardiac anomalies. Venlafaxine exposure decreased placental expression of the serotonin transporter (SERT/Slc6a4) at the transcript and protein levels. In contrast, venlafaxine increased SERT expression in the hearts of female, but not male, fetuses. Expression of the serotonin 2B receptor (5-HT2B /Htr2b) and of fibroblast growth factor 8 was induced in fetal hearts. CONCLUSION: In utero venlafaxine exposure altered the placental index and induced fetal cardiac anomalies in rats. We propose that the increased incidence of cardiac anomalies is mediated through alterations in serotonin signaling in the placenta and fetal heart. Birth Defects Research (Part A), 2016. (c) 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:1044-1055, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27384266 TI - Determination of Key Hydrocarbon Autoxidation Products by Fluorescence. AB - Hydroperoxides and carboxylic acids are key primary products that arise in the autoxidation of hydrocarbons. We have developed a simple approach to rapidly and simultaneously determine both types of products using hydroperoxide- and acid sensitive moieties conjugated to nonpolar coumarin- and BODIPY-based fluorophores. The coumarin- and BODIPY-conjugated amine probes described here undergo 38- and 8-fold enhancement, respectively, upon protonation in a solvent system compatible with heavy hydrocarbons. The latter can be used directly with our previously described hydroperoxide-sensitive coumarin-conjugated phosphine probe to enable rapid quantification of both carboxylic acids and hydroperoxides in hydrocarbon samples. The utility of the approach is illustrated by the ready determination of the differing relative rates of hydroperoxide and acid formation with changes in hydrocarbon structure (e.g., n-hexadecane vs 1-hexadecene vs a lubricant base stock). The method offers significant versatility and automation compared with common but laborious titration approaches, and greatly improves screening efficiency and accuracy for the identification of novel radical trapping antioxidants for high temperature applications. This application was demonstrated by the automated analysis of hydroperoxides and carboxylic acids (by microplate reader) in samples from 24 inhibited autoxidations of a lubricating oil, which were carried out on a parallel synthesizer at 160 degrees C in triplicate in a single day. PMID- 27384269 TI - Qualitative research in health: contributions to education, profession, family, citizenship and social interaction. PMID- 27384267 TI - The mechanical response of talin. AB - Talin, a force-bearing cytoplasmic adapter essential for integrin-mediated cell adhesion, links the actin cytoskeleton to integrin-based cell-extracellular matrix adhesions at the plasma membrane. Its C-terminal rod domain, which contains 13 helical bundles, plays important roles in mechanosensing during cell adhesion and spreading. However, how the structural stability and transition kinetics of the 13 helical bundles of talin are utilized in the diverse talin dependent mechanosensing processes remains poorly understood. Here we report the force-dependent unfolding and refolding kinetics of all talin rod domains. Using experimentally determined kinetics parameters, we determined the dynamics of force fluctuation during stretching of talin under physiologically relevant pulling speeds and experimentally measured extension fluctuation trajectories. Our results reveal that force-dependent stochastic unfolding and refolding of talin rod domains make talin a very effective force buffer that sets a physiological force range of only a few pNs in the talin-mediated force transmission pathway. PMID- 27384268 TI - Risk factors and a clinical prediction model for low maternal thyroid function during early pregnancy: two population-based prospective cohort studies. AB - BACKGROUND: Low maternal thyroid function during early pregnancy is associated with various adverse outcomes including impaired neurocognitive development of the offspring, premature delivery and abnormal birthweight. AIM: To aid doctors in the risk assessment of thyroid dysfunction during pregnancy, we set out to investigate clinical risk factors and derive a prediction model based on easily obtainable clinical variables. METHODS: In total, 9767 women during early pregnancy (<=18 week) were selected from two population-based prospective cohorts: the Generation R Study (N = 5985) and the ABCD study (N = 3782). We aimed to investigate the association of easily obtainable clinical subject characteristics such as maternal age, BMI, smoking status, ethnicity, parity and gestational age at blood sampling with the risk of low free thyroxine (FT4) and elevated thyroid stimulating hormone (TSH), determined according to the 2.5th 97.5th reference range in TPOAb negative women. RESULTS: BMI, nonsmoking and ethnicity were risk factors for elevated TSH levels; however, the discriminative ability was poor (range c-statistic of 0.57-0.60). Sensitivity analysis showed that addition of TPOAbs to the model yielded a c-statistic of 0.73-0.75. Maternal age, BMI, smoking, parity and gestational age at blood sampling were risk factors for low FT4, which taken together provided adequate discrimination (range c statistic of 0.72-0.76). CONCLUSIONS: Elevated TSH levels depend predominantly on TPOAb levels, and prediction of elevated TSH levels is not possible with clinical characteristics only. In contrast, the validated clinical prediction model for FT4 had high discriminative value to assess the likelihood of low FT4 levels. PMID- 27384270 TI - Understanding the curriculum the light of training guiding health in Brazil. AB - OBJECTIVE: To analyze Pedagogical Projects Courses (PPCs) from the healthcare field in light of the National Curriculum Standards (NCS) policies on healthcare training. METHOD: Exploratory descriptive study of qualitative approach, in which were carried out analyzes of PPPs of Nursing, Pharmacy, Medicine, Nutrition and Dentistry of a federal university in the Midwest region of Brazil. As technical analysis of documentary sources, adopted the content analysis in the thematic mode. RESULTS: The analysis of PPC showed the general aspects of PPC as the course features the historical percursso and construction, professional skills and competences required for professional performance and the guiding principles of formation characterized by technical, professional practice, articulation theory/ practice, interdisciplinarity and ethical / social training. CONCLUSIONS: PPC presented is consistent with the proposals set out in DCN and carry training policies in health in Brazil, providing adequate training for health professionals, the demands of the population and the National Health System. OBJECTIVO: Analisar os Projetos Pedagogicos de Cursos (PPC) da area da saude a luz das Diretrizes Curriculares Nacionais (DCN) e das politicas indutoras de formacao em saude do Brasil. METODO: Pesquisa descritiva exploratoria de abordagem qualitativa, na qual foram realizadas analises dos PPC dos cursos de Enfermagem, Farmacia, Medicina, Nutricao e Odontologia de uma instituicao federal de ensino superior da regiao Centro-Oeste do Brasil. Como tecnica de analises das fontes documentais, adotou-se a analise de conteudo, na modalidade tematica. RESULTADOS: As analises dos PPC evidenciaram os aspectos gerais dos PPC como as caracteristicas do curso, o percursso historico e sua construcao, habilidades e competencias profissionais requeridas para o desempenho profissional e os principios norteadores da formacao caracterizados pela tecnica, pratica profissional, articulacao teoria/pratica, interdisciplinaridade e formacao etica/social. CONCLUSAO: Os PPC apresentaram-se condizentes com as propostas previstas nas DCN e com as politicas indutoras de formacao em saude do Brasil, proporcionando a formacao adequada para os profissionais de saude, as demandas da populacao e do Sistema Unico de Saude. PMID- 27384271 TI - Analysis of Service-learning activities adopted in health courses of Federal University of Bahia. AB - is study aimed to raise and discuss the data about the integration of health courses teaching and service activities o ered at the Federal University of Bahia (UFBA), pre- senting scenarios practices and major di culties existing in the relationship between the university and the services of health. is was a qualitative study of descriptive explo- ratory character, using a questionnaire as a research tool applied to the coordinators of selected health courses. e selection was by reading the political pedagogical project, the following courses were selected: nursing, physical therapy, speech therapy, medicine, nu- trition, dentistry and public health. e results indicated eight types of teaching-service integration activities, 57 scenarios of practice and the main di culties. It was concluded that these courses are sticking to changes in academic training in health, in view of the large number of basic health units in the teaching service process. us, it emphasizes that the UFBA includes activities in health care that enable the integration-education in the higher education process, although there are some di culties in this relationship indicated by the coordinators. Esse estudo teve como objetivo levantar e discutir os dados acerca das atividades de integracao ensino-servico de cursos de saude oferecidos na Universidade Federal da Bahia (UFBA), apresentando os cenarios de praticas e as principais di culdades existentes na relacao entre a uni- versidadeeosservicosdesaude.Tratou sedeumapesquisaqualitativa,decaraterdescritivoexploratorio,utilizando seumquestionariocomo instrumento de investigacao aplicado aos coordenadores dos cursos de saude selecionados. A selecao foi mediante a leitura do projeto politico pedagogico, sendo selecionados os seguintes cursos: enfermagem, sioterapia, fonoaudiologia, medicina, nutricao, odontologia e saude coletiva. Os resultados indicaram 8 tipos de atividades de integracao ensino-servico, 57 cenarios de pratica e as principais di culdades. Concluiu-se que esses cursos estao aderindo as mudancas na formacao academica em saude, tendo em vista o grande numero de unidades basicas de saude que integram o processo de ensino servico. Dessa forma, ressalta-se que a UFBA contempla atividades na area de saude que viabilizam a integracao-ensino no processo de formacao superior, embora existam algumas di culdades nesta relacao apontadas pelos coordenadores. PMID- 27384272 TI - Medical training and nurses of Family Health strategy on worker health aspect. AB - Considering the worker's health one of the Unified Health System (SUS) tasks, the Primary Health Care (PHC) and the Family Health Strategy (FHS) play an important role in the development of health actions in the field health-work. In Brazil, where the number of informal and domiciled jobs is high, the FHS becomes a reference in the workers' health actions. Therefore, if the FHS is not attentive to the relation between professional occupation and disease, several diseases that affect workers can overload the system without obtaining a cure. The aim of this study is to evaluate doctors and nurses recognition of the Family Health Strategy on occupational diseases in Aparecida de Goiania. This is a qualitative descriptive study and the data analysis was done by content analysis. The setting for this study contemplates FHS units in the municipality of Aparecida de Goiania, Goias. There were 8 Basic Health Units and 16 health professionals were interviewed. The data was collected in the participants of the interview workplaces, from February through April, 2013, after being approved by the Ethics and Research Committee. The discourses were analyzed according to Minayo (2007), using thematic analysis. The interviews were recorded and later transcribed for analysis. Among the 16 professionals interviewed we observed that only 3 (18.75%) received professional training on occupational health in their Institution, however the aim of the courses were towards situations of biological hazards and not about workers care. Practitioners reported lack of knowledge in the occupational health area, and also observed that the area is still undervalued and underexplored in the academic and professional fields, and even by the Municipality health management. Evaluating the academic education it is possible to observe the inadequacy of the subject workload, where professionals reported the lack of knowledge in the area and the low workload of the subject in the academic field. CONCLUSION: There is a need to raise awareness and interest of the municipality health managers and the health professionals, doctors and nurses, towards the relations work-health-disease and the need to capacitate these professionals, in order to assist the workers in a better way. Considerando a saude do trabalhador uma das atribuicoes do Sistema Unico de Saude (SUS), a Atencao Primaria a Saude (APS) e a Estrategia Saude da Familia (ESF) assumem papel importante no desenvolvimento de acoes no campo saude-trabalho. No Brasil, como e grande o numero de trabalhos informais e domiciliados, a ESF se torna referencia nas acoes de saude do trabalhador. Assim, se a ESF nao estiver atenta a relacao entre atividade profissional e o adoecimento, varias doencas que acometem os trabalhadores podem sobrecarregar o sistema sem a obtencao de cura. O objetivo deste estudo foi avaliar o reconhecimento de medicos e enfermeiros da Estrategia Saude da Familia de Aparecida de Goiania sobre doencas ocupacionais. Trata-se de um estudo qualitativo descritivo, a analise dos dados foi feita pela analise de conteudo. O cenario deste estudo constitui-se das unidades de ESF do municipio de Aparecida de Goiania, Goias. Foram 8 Unidades Basicas de Saude selecionadas e 16 profissionais de saude entrevistados. Os dados foram coletados nos respectivos locais de trabalho dos participantes da entrevista, nos meses de fevereiro a abril de 2013, apos aprovacao pelo Comite de Etica e Pesquisa. Os discursos foram analisados de acordo com Minayo (2007), utilizando a analise tematica. As entrevistas foram gravadas e posteriormente, transcritas para sua analise. Dos 16 profissionais entrevistados, observamos que somente 3 (18,75%) passaram por capacitacao profissional em saude do trabalhador na Instituicao, porem os cursos eram voltados para situacoes de riscos biologicos e nao para o atendimento ao trabalhador. Os profissionais relataram falta de conhecimento na area de saude do trabalhador, observaram o quanto a area ainda e desvalorizada e pouco explorada no meio academico, profissional e ate mesmo pela gestao de saude do municipio. Na avaliacao da formacao academica e possivel observar a inadequacao da carga horaria da disciplina, onde os profissionais relataram o pouco conhecimento na area, a baixa carga horaria da disciplina na area academica. Conclusao: Observa-se a necessidade de despertar o interesse dos gestores de saude do municipio e dos profissionais, medicos e enfermeiros, para as relacoes trabalho-saude-doenca e a necessidade de capacitacao desses profissionais para o melhor atendimento ao trabalhador. PMID- 27384273 TI - The development of communication skills and the teacher's performance in the nursing student's perspective. AB - OBJECTIVE: To understand experiences in the development of communication skills and the teacher's role in this teaching-learning process under the perspective of undergraduate nursing students by considering two types of curriculum organization. METHOD: Descriptive study with a qualitative approach conducted in two public schools located in Sao Paulo state, Brazil. Data were collected by means of self-completed forms from 81 students in the second and fourth years of the undergraduate program. Results were analyzed in light of Content Analysis. RESULTS: Results showed that the development of such skills is related to: students' individual characteristics, patients' characteristics, those of the health-disease process, the health-care team's profile and the theoretical knowledge acquired on communication in health-care provision and nursing. The teacher's role was perceived as one that supports and encourages interactions with patients and health-care teams by teaching and providing orientation about interpersonal communication. CONCLUSIONS: Students identify and value the importance of their teachers' performance in the development and acquisition of communication skills. Additionally, students who experience active teaching learning methodologies acknowledge the teacher as essential to provide opportunities for students to express their knowledge and thoughts. OBJETIVO: Compreender, sob a otica de graduandos de enfermagem, as experiencias no desenvolvimento de habilidades comunicativas e a atuacao do professor neste processo de ensino-aprendizagem, considerando dois tipos de organizacao curricular. METODO: Pesquisa descritiva com abordagem qualitativa, realizada em duas instituicoes de ensino publicas, situadas no interior do estado de Sao Paulo, Brasil. A coleta dos dados foi realizada pelo autopreenchimento de formulario por 81 alunos de segundo e quartos anos da graduacao. Os resultados foram analisados a luz da Analise de Conteudo. RESULTADOS: Revelaram que o desenvolvimento desta habilidade esta relacionado a: caracteristicas individuais dos alunos, dos pacientes, do processo saude-doenca, perfil da equipe e dos conhecimentos teoricos sobre comunicacao em saude e em enfermagem. O papel do professor foi percebido apoiando e incentivando as interacoes com pacientes e equipes de saude e ensinando e orientando sobre comunicacao interpessoal. CONCLUSAO: Os alunos identificam e valorizam a importancia da atuacao de seus professores no desenvolvimento e aquisicao de habilidades comunicativas. Alem disso, os estudantes que vivenciaram as metodologias ativas de ensino aprendizagem reconhecem o docente essencial para oportunizar a expressao de conhecimentos e pensamentos dos alunos. PMID- 27384274 TI - Perception of nursing faculty on the care: Heidegger constructions. AB - OBJECTIVE: To understand the perceptions of nursing teachers about care in the light of Heidegger's framework. It was used as theoretical and methodological reference Hei- degger's hermeneutics. METHOD: To capture the meanings we used phenomenological interviews with 11 teachers. e data analysis is based on heideggerian hermeneutic. RESULTS: The way to be a nurse determines their way of life to the care that re ects the construction of experiences in the nursing worldliness. The existence of the nurse for nursing care is evidenced in care relations established between being careful and being caregiver, deciding the mode of being-there of the nurse who has before him and on the other the possibilities of care. CONCLUSIONS: It is being in the world that the being-nurse is manifested in their subjectivity in care for sensitive, is the objectivity of scienti c care, and is in the interrelationship with being careful is that manifests the being of choices and existing decisions in his way of being. OBJETIVO: Compreender as percepcoes dos docentes de enfermagem sobre o cuidado a luz do referencial de Heidegger. Utilizou-se como referencial teorico metodologico hermeneutica heideggeriana. METODO: Para captar os significados utilizou-se entrevista fenomenologica realizada com 11 docentes. A analise dos dados baseou-se na hermeneutica heideggeriana. RESULTADOS: O modo de ser enfermeiro determina seu modo de ser para o cuidado, que e reflexo da construcao das experiencias na mundaneidade da enfermagem. A existencia do ser enfermeiro para o cuidado de enfermagem e evidenciado nas relacoes de cuidado estabelecidas entre o ser cuidado e o ser cuidador, decidindo o modo de ser-ai do enfermeiro que tem diante de si e do outro as possibilidades de cuidado. CONCLUSAO: E ser-no mundo que o ser-enfermeiro se manifesta, em sua subjetividade no cuidar sensivel, e na objetividade do cuidar cientifico, e e na inter-relacao com o ser cuidado e que manifesta o ser de escolhas e decisoes existindo em seu modo de ser. PMID- 27384275 TI - The Illness Experience: Palliative Care Given the impossibility of Healing. AB - This paper presents a reflection about being terminally ill and the various ways that the subject has at its disposal to deal with this event. The objective is to understand the experience of palliation for patients undergoing no therapeutic possibilities of cure. The methodology of this study has the instruments to semi structured interview, the participant observation and the field diary, and the Descriptive Analysis of Foucault's inspiration how the narratives of the subjects were perceived. The Results of paper there was the possibility of looking at the experience of illness through the eyes of a subject position assumed by the very sick. As conclusion we have than when choosing palliative care, the terminally ill opts for a way to feel more comfortable and resists the impositions of the medical model of prolonging life. O presente trabalho traz uma reflexao a respeito do ser um doente terminal e das varias maneiras que o sujeito tem a seu dispor para lidar com esse acontecimento. Nosso objetivo foi compreender a experiencia da paliacao por sujeitos doentes sem possibilidades terapeuticas de cura. A metodologia deste estudo teve como instrumentos a Entrevista Narrativa, a Observacao Participante e o Diario de Campo, sendo a Analise Descritiva de inspiracao foucaultiana o modo como as narrativas dos sujeitos foram percebidas. O resultado do estudo mostrou a possibilidade de olhar a experiencia do adoecer atraves da otica de uma posicao de sujeito assumida pelo proprio enfermo. E concluimos que ao escolher os cuidados paliativos, o doente terminal opta por um modo de se sentir mais confortavel e resiste as imposicoes do modelo medico de prolongamento da vida. PMID- 27384276 TI - The applicability of the concept of treatment adherence in the context of the Brazilian mental health system. AB - OBJECTIVE: To present reflections on the type of research conducted on a treatment adherence among users of Public Mental Health System in Brazil and discuss the applicability of the concept of adherence to treatment in this context. METHOD: Literature review in SciELO, LILACS, Cochrane Library and PubMed / MEDLINE using the Health Sciences Descriptors (DeCS) treatment, adhesion and "mental health" and the specific vocabulary of the Medical Subject Headings (MeSH) "patient compliance/psychologist" y "mental health". They were included for review the complete texts and theses published between 2007-2012 in Portuguese, English and Spanish. RESULTS: 127 articles were recovered, 32 specifically related to mental health. Eight were excluded for duplicates and after reading the remaining 24 articles were selected for this study 10 conducted in the field of Mental Health in Brazil. No investigations have been identified with focus on adherence to psychosocial treatment offered in public mental health. CONCLUSIONS: disregard of the mental health legislation and reinforce the asylum model of assistance. OBJETIVO: Presentar reflexiones sobre el tipo de investigaciones realizadas en Brasil sobre la adhesion al tratamiento de los usuarios del Sistema Publico de Salud Mental y discutir la aplicabilidad del concepto de adhesion al tratamiento en dicho contexto. METODO: Revision bibliografica en las bases SciELO, LILACS, Biblioteca Cochrane y PubMed/MEDLINE utilizando los descriptores de Ciencias de la Salud (DeCS) adhesion, tratamiento y "salud mental" y el vocabulario especifico de Medical Subject Headings (MeSH) "patient compliance/psychologist" y "mental health". Se incluyeron los textos completos y las tesis publicadas entre 2007-2012, en portugues, ingles y espanol. RESULTADOS: F1eron recuperados 127 articulos, 32 especificamente de la salud mental. Se excluyeron los 8 duplicados y de los 24 restantes fueron seleccionados para el presente trabajo los 10 realizados en Brasil. No se identificaron enfoques sobre la adhesion al tratamiento de perspectiva psicosocial ofrecido en la red publica de salud mental. CONCLUSION: Las investigaciones analizadas desconsideran el contexto y la complejidad del tratamiento ofrecido desconociendo la legislacion en salud mental vigente y reforzando el modelo de atencion asilar. PMID- 27384277 TI - Perception of hypertensive patients about their non-adherence to the use of medication. AB - This qualitative study aims to analyze the perception of patients with hypertension on their non-adherence to medication. 13 participants were interviewed, classified as non-adherent.The analysis was performed using the technique of thematic content analysis. Data points to contradictions in the approach of what is being adherent or not, the difficulty of adhering to the use of medication due to lifestyle habits, that forgetting is understood as a justification for non-compliance, and reinforces factors that hinder such practice, such as the use of many drugs, the presence of signs and symptoms and changes in daily routine. With complex conditions that involve non-adherence to treatment and the current context of the predominance of chronic diseases, it is essential to invest in innovative strategies of care for such people. Estudo qualitativo que se propoe a analisar a percepcao do portador de hipertensao arterial sobre a sua nao adesao ao tratamento medicamentoso. Foram entrevistados treze participantes classificados como nao aderente. A analise foi realizada pela tecnica de analise de conteudo modalidade tematica. Os dados apontam para contradicoes na abordagem sobre o que e ser ou nao aderente, a dificuldade de aderir ao uso dos medicamentos devido ao habito de vida, que o esquecimento e compreendido como uma justificativa para a nao adesao, alem de reforcarem fatores que dificultam tal pratica, como o uso de muitos medicamentos, presenca de sinais e sintomas e mudancas na rotina diaria. As complexas condicoes que envolvem a nao adesao ao tratamento e ao o atual contexto de predominio de doencas cronicas, e primordial que se invista em estrategias inovadoras de cuidado a tais pessoas. PMID- 27384278 TI - Social Representations of Gynecologic Cancer Screening Assessment a Qualitative research on Ecuadorian women. AB - The purpose of this work was to explore: knowledge, attitudes, and beliefs regarding gynecologic cancer screening on Ecuadorian women users of primary care facilities, to identify the social representations that users of health services make about these programs and their influence on the decision to undergo a screening. An exploratory and qualitative research design was held using focus groups and in-depth interviews for data collection. A narrative content analysis of the results was conducted. Women's knowledge on gynecological cancer screening was confusing. Most frequent misconceptions related to the pap smear were: the belief that it could be useful for detecting pregnancy, ovarian cysts or infections. Most of the participants stated that the pap smear procedure is a traumatic and painful experience. Regarding to mammography women said it was used for sick woman and this procedure by itself may cause cancer. El proposito de esta investigacion fue explorar los conocimientos, actitudes y creencias respecto a los programas de deteccion del cancer ginecologico entre usuarias de centros de atencion primaria de salud para identificar las representaciones sociales que las usuarias de los servicios de salud elaboran acerca de estos programas y de los diferentes procedimientos que comprenden. El diseno de la investigacion fue exploratorio y cualitativo, mediante grupos focales y entrevistas a profundidad, con el respectivo analisis narrativo e interpretativo del contenido. Se encontro conocimiento confuso acerca de los programas de tamizaje de cancer ginecologico y dificultades asociadas a la realizacion de los procedimientos. Los significados mas frecuentes acerca de los programas fueron: el uso de la citologia cervico vaginal para detectar embarazo, quistes ovaricos o infecciones. La mayoria de los participantes asociaba este procedimiento con una experiencia dolorosa y traumatica. Respecto al autoexamen de mamas, lo calificaron como un masaje preventivo-terapeutico y a la mamografia como peligrosa porque podria desarrollar cancer. PMID- 27384279 TI - 30 years later: Social Representations about AIDS and sexual practices of rural towns residents. AB - In the 30 years of the AIDS pandemic in Brazil, it is recognized the HIV virus internalization of the phenomenon as a challenge to care and current health policies. In this sense, it aimed to verify sex practices and social representations that rural towns residents have about the disease. Attended by 789 people, men and women, between 18 and 90 years old, residents in 41 towns with fewer than 11,000 inhabitants in the state of Paraiba / Brazil. Data were collected by a questionnaire and the free association of words test. The results showed low concern about disease, perception of invulnerability to HIV infection and not using condoms during sexual intercourse, and confidence in the major reason related partner. Also showed endure derogatory and stereotypical representations, revealing that still persist in rural areas, beliefs and representations concerning the beginning of the epidemic. From these findings, it is possible to point out deficiencies in the care provided by the health services in these localities, which may result in increased vulnerability of this population to diseases, so there is the need to intensify information campaigns and intervention. The results reveal the existence of three different types of modes of learning health literacy skills in informal context: : i) learning that takes place in action, in achieving daily tasks; ii) learning processes that result from problem solving; iii) learning that occurs in an unplanned manner, resulting from accidental circumstances and, in some cases, devoid of intentionality. Nos 30 anos da pandemia da Aids no Brasil, reconhece-se o fenomeno da interiorizacao do virus HIV como um desafio ao cuidado e as politicas de saude atuais. Neste sentido, objetivou-se conhecer praticas sexuais e as representacoes sociais que residentes de cidades rurais tem acerca da doenca. Participaram 789 pessoas, homens e mulheres, entre 18 e 90 anos de idade, residentes em 41 cidades com menos de 11.000 habitantes no estado da Paraiba/Brasil. Os dados foram coletados por um meio de um questionario e o teste de associacao livre de palavras. Os resultados mostraram baixa preocupacao com doenca, percepcao de invulnerabilidade a contaminacao pelo HIV e o nao uso do preservativo nas relacoes sexuais, sendo a confianca no parceiro o principal motivo relacionado. Tambem mostraram perdurar representacoes de natureza pejorativa e estereotipada, revelando que ainda perduram, no meio rural, crencas e representacoes referentes ao inicio da epidemia. A partir de tais achados, e possivel apontar deficiencias em termos de cuidados oferecidos pelos servicos de saude nestas localidades, o que pode resultar em maiores vulnerabilidades dessa populacao ao adoecimento, havendo assim a necessidade da intensificacao de campanhas de informacao e intervencao. PMID- 27384280 TI - The family experience of care in chronic situation. AB - An essay that aims to reflect on the family experience of care in chronic situation, increasing the understanding of the family as the primary caregiver. It is based on comprehensive approach in studies conducted in three matrix searches from family care experiences. We have taken three axes to organize our reflections: a) conformation of family care in chronic situation, highlighting the multiple costs incurred to the family, which can exhaust the potential of care and establish or increase its vulnerability if it is not backed by networks support and sustenance; b) family rearrangements for the care, giving visibility to care cores in which many loved family members share the care, dynamic, plural and changeable way; c) self care modeling family care, pointing to the range of possibilities of the person taking care of diseased conditions supported by people close to them. We learn that the family takes care of itself in everyday life and in the illness experience, creating networks that can provide you support and sustenance. Thus, professionals in health practices should shape up in a longitudinal and very personal way, by reference to the family care, supporting him in what is his own. Ensaio que tem por objetivo refletir sobre a experiencia familiar de cuidado na situacao cronica, ampliando a compreensao da familia como cuidadora primaria. Embasa-se em estudos de abordagem compreensiva realizados em tres pesquisas matriciais que abordaram experiencias familiares de cuidado. Tomamos tres eixos para organizar nossas reflexoes: a) conformacao do cuidado familiar na situacao cronica, destacando os multiplos custos gerados a familia, que podem exaurir seus potenciais de cuidado, instaurando ou ampliando sua vulnerabilidade se nao for amparada por redes de apoio e sustentacao; b) rearranjos familiares para o cuidado, dando visibilidade aos nucleos de cuidado compartilhados pelos diversos entes familiares, de modo dinamico, plural e mutavel; c) cuidado proprio modelando o cuidado familiar, apontando a gama de condicoes de possibilidades da pessoa adoecida se cuidar apoiada pelas pessoas que lhe sao proximas. Compreendemos que a familia cuida de si e de seus entes no bojo da vida, assim como na experiencia de adoecimento, tecendo redes que a sustentem ao longo do tempo. As praticas profissionais em saude precisam modelar se, entao, tendo por referencia o cuidado familiar, amparando-o naquilo que lhe seja proprio. PMID- 27384281 TI - Moral Distress in Family Health Strategy: experiences expressed by daily life. AB - OBJECTIVE: Understanding the Moral Suffering experiences expressed in the daily life of the Family Health Strategy. METHOD: This is a case study with a qualitative approach, conducted between August and October 2014 in a municipality of Minas Gerais. The sample was represented by 28 professionals of family health teams. Data were collected through interviews with semi-structured questionnaires, observation, projective technique and submitted to thematic content analysis. RESULTS: The results indicate that routine issues of the health care system lead professionals to experience a challenging practice in dealing with daily situations that contradict their ethical precepts and can compromise the quality of work, becoming triggers of Moral Distress. CONCLUSIONS: Social vulnerabilities such as domestic violence, poor socioeconomic conditions and organizational weaknesses of the health system were the main triggers of Moral Distress. Therefore, it is necessary to amplify this reflection by workers of the Family Health Strategy, aiming to encourage the minimization of suffering experiences, considering their ethical values. OBJETIVO: Compreender as vivencias de Sofrimento Moral expressas no cotidiano da Estrategia de Saude da Familia. METODO: Trata-se de um estudo de caso com abordagem qualitativa, realizado entre os meses de agosto a outubro de 2014, cujo cenario foi um municipio de Minas Gerais. Participaram 28 profissionais das equipes de saude da familia. Os dados foram coletados por meio de entrevistas com roteiro semiestruturado, observacao, tecnica projetiva e, submetidos a analise de conteudo tematica. RESULTADOS: Os resultados apontaram que as questoes rotineiras do servico de saude levam os profissionais a vivenciarem uma pratica desafiadora ao lidarem diariamente com situacoes que contradizem seus preceitos eticos capazes de comprometer a qualidade do trabalho tornando-se disparadores de Sofrimento Moral. CONCLUSAO: As vulnerabilidades sociais, como violencia domestica e condicoes socioeconomicas precarias, alem das fragilidades organizacionais do Sistema de Saude, foram os principais geradores de Sofrimento Moral. Assim, considera-se necessaria a reflexao ampliada sobre a tematica por parte dos trabalhadores da Estrategia de Saude da Familia, com intuito de propiciar a minimizacao de vivencias de sofrimento e uma pratica profissional em consonancia com seus valores eticos. PMID- 27384282 TI - Changing dietary habits among Akwen Xerente. AB - The research aimed to identify the current feed of Xerente people in Indian villages Porteira and Funil in the city of Tocantinia / TO. It was used a qualitative ethnographic approach. Conducted from September 2013 to August 2014. The data were presented in a diary, through participant observation of food practices with the guidance of a script. A process of dietary change that permeates the culture of this people is taking place. Factors such as the deficit in the planting gardens, the recent arrival of energy, and therefore the technology has allowed access to processed foods. But some families still maintain the farming of cassava, yam, and beans. The main animals that are hunted in the village are peccary, deer and armadillo. It was possible to point which foods are inserted in the Xerente feed and factors related to this situation. A pesquisa objetivou identificar a alimentacao atual do povo Xerente, nas aldeias indigenas Porteira e Funil, no municipio de Tocantinia / TO. Utilizou-se uma abordagem etnografica qualitativa. Realizada entre setembro de 2013 a agosto de 2014. Os dados foram descritos atraves de um diario de campo, por meio da observacao das praticas alimentares com a orientacao de um roteiro. Esta ocorrendo um processo de mudanca alimentar na cultura deste povo. Fatores como o deficit no plantio das rocas, a chegada da energia, e consequentemente a tecnologia, permitiu o acesso a alimentos industrializados. Mas algumas familias ainda mantem o cultivo de mandioca, inhame, feijao andu. Os principais animais que sao cacados na aldeia sao caititu, veado e tatu. Foi possivel encontrar a presenca de alimentos industrializados inseridos na alimentacao do Xerente e isso tem provocado alteracoes nos habitos desse povo. PMID- 27384283 TI - Minimum Map of Social Institutional Network: a multidimensional strategy for research in Nursing. AB - OBJECTIVE: To analyze the use of methodological strategies in qualitative research - Minimum Maps of Social Institutional Network, as proposed to understand the phenomena in the multidimensional perspective. METHOD: Methodological theoretical essay in which we aimed to reflect on the use of innovative methodological strategies in nursing research, supported in Complex Paradigm fundamentals. RESULTS: The minimum map of Social Institutional External Network aims to identify institutional linkages and gaps for the intervention work of the surveyed institutions. The use of these maps provided important advances in know-how qualitative research in Health and Nursing. CONCLUSIONS: In this perspective, the use of minimum Social Intitutional Network maps can be stimulated and enhanced to meet the current demands of the contemporary world, particularly for its flexibility in adapting to various research subjects; breadth and depth of discussion; and possibilities with health services. OBJETIVO: Analisar o uso de estrategias metodologicas em pesquisas qualitativas - Mapa minimo da Rede Social Institucional, como proposta para compreender os fenomenos na perspectiva multidimensional. METODO: Ensaio teorico metodologico em que buscou-se refletir sobre o uso de estrategias metodologicas inovadoras de pesquisa na enfermagem, sustentada nos fundamentos do Pensamento Complexo. RESULTADOS: O mapa minimo da Rede Social Institucional Externa tem o objetivo de identificar os vinculos institucionais e lacunas para o trabalho de intervencao das instituicoes pesquisadas. O uso destes mapas proporcionou avancos importantes no saber-fazer pesquisa qualitativa em Saude e Enfermagem. CONCLUSAO: Nessa perspectiva, o uso de mapas minimos da Rede Social Institucional pode ser estimulado e potencializado para responder as atuais demandas da contemporaneidade, em especial pela sua flexibilidade na adequacao a diversos objetos de pesquisa; amplitude e profundidade de discussao; e possibilidades de articulacao com a pratica dos servicos. PMID- 27384284 TI - Social Networking Family of Caregivers during Hospitalization of Children. AB - OBJECTIVE: To identify and analyze the significant networks of family, social and hospital support described by the family caregivers of hospitalized children 5-12 years during the hospital stay. METHOD: Descriptive study, exploratory and qualitative study conducted with 20 caregivers of children hospitalized in a hospital in a city in southern Brazil, through semi-structured interviews and significant social networks maps, tailored to the hospital setting. RESULTS: Data analysis showed that the most active social network was comprised of families through emotional support, material aid and services. Relations with hospital health care team and the hospital context were cited as providing support to the caregivers of the hospitalized child. CONCLUSIONS: The identification of social networks in the child's hospitalization course enables equip professionals working in the institution aiming at better targeting of actions and care for the family and hospitalized children. OBJETIVO: Identificar e analisar as redes significativas de suporte familiar, social e hospitalar descritas pelos familiares acompanhantes de criancas hospitalizadas de 5 a 12 anos, durante o periodo de internacao. METODO: Estudo descritivo, exploratorio e de cunho qualitativo realizado com 20 acompanhantes de criancas hospitalizadas em uma unidade hospitalar em uma cidade do Sul do Brasil, por meio de entrevistas semiestruturadas e dos Mapas de Redes sociais significativas, adaptado para o contexto hospitalar. RESULTADOS: A analise dos dados demonstrou que a rede social mais atuante foi composta por familiares, atraves de apoio emocional, ajuda material e de servicos. As relacoes com a equipe de saude do hospital e com o contexto hospitalar foram citadas como capazes de fornecer apoio ao acompanhante da crianca internada. CONCLUSAO: a identificacao das redes sociais no curso da hospitalizacao da crianca possibilita instrumentalizar os profissionais que atuam na instituicao objetivando um melhor direcionamento de acoes e cuidados destinados a familia e a crianca hospitalizada. PMID- 27384285 TI - Educational topics for school from the perspective of professionals in the Mobile Emergency Service. AB - OBJECTIVE: To systematize, with professionals from the Mobile Emergency Care Service of Santa Catarina municipality, the main issues for the development of an educational tool of attention to the emergency room, dedicated to the school-age population. METHOD: Qualitative study, conducted through meetings in the focus group format, with 19 professionals who develop their activities in the city Emergency Mobile Emergency Service. Data were categorized and analyzed using thematic analysis technique. RESULTS: The contents discussed at the meetings were grouped into four thematic categories: The Mobile Emergency Service and the school: education and health promotion for children; As the Mobile Emergency Care Service works: What is important to know ?; Something's wrong, what now? and; We are nearly finished, give your opinion. CONCLUSIONS: The specific issues arising from the meetings contributed to the production of an educational tool on the activities of the Mobile Emergency Service, which may be used by the School Health Program to promote health education in the care area to the emergency room with the population schoolchildren. OBJETIVO: Sistematizar, junto aos profissionais do Servico de Atendimento Movel de Urgencia de um municipio catarinense, os principais temas para a elaboracao de um instrumento educativo sobre atencao as urgencias, dedicado a populacao em idade escolar. METODO: Estudo qualitativo, realizado por meio de encontros no formato de grupo focal, com 19 profissionais que desenvolvem suas atividades no Servico de Atendimento Movel de Urgencia municipal. Os dados foram categorizados e analisados com a tecnica de analise tematica. RESULTADOS: Os conteudos debatidos nos encontros foram agrupados em quatro categorias tematicas: O Servico de Atendimento Movel de Urgencia e a escola: educacao e promocao da saude para as criancas; Como o Servico de Atendimento Movel de Urgencia funciona: o que e importante saber?; Tem algo errado, e agora? e; Estamos quase concluindo, de sua opiniao. CONCLUSAO: Os temas especificos resultantes dos encontros contribuiram para a producao de um instrumento educacional sobre as atividades do Servico de Atendimento Movel de Urgencia, que podera ser utilizado pelo Programa Saude na Escola para promover educacao em saude na area de atencao as urgencias junto a populacao em idade escolar. PMID- 27384286 TI - Taking care of the newborn dying and their families: Nurses' experiences of neonatal intensive care. AB - OBJECTIVE: To understand the experiences of nurses when caring for dying newborns and their families in the NICU; and redeem their perceptions about acting before the death and grieving process. METHOD: A descriptive exploratory study with a qualitative approach, developed with nine nurses at the ICU of a hospital in Sao Paulo (SP), Brazil. Data was collected through semi-structured interviews and analyzed using the Collective Subject Discourse (CSD). RESULTS: Caring for newborns who are dying and their families is very difficult for nurses, due to the intense involvement. They seek strategies to deal with the situation and, before the newborn's death, despite the suffering, express the feeling of accomplishment. CONCLUSIONS: Facing death and grief triggers mechanisms that emerge life references, coming across painful issues. Learning to deal with these questions is a daily challenge for nurses of the NICU. OBJETIVO: Compreender as experiencias vivenciadas por enfermeiros ao cuidar de neonatos que estao morrendo e seus familiares na UTIN; e resgatar as suas percepcoes sobre a atuacao diante do processo de morte e luto. METODO: Estudo descritivo exploratorio, de abordagem qualitativa, desenvolvido com nove enfermeiras da UTIN de um hospital de Sao Paulo (SP), Brasil. Os dados foram coletados por meio de entrevista semi estruturada e analisados pela tecnica do Discurso de Sujeito Coletivo (DSC). RESULTADOS: Cuidar de neonatos que estao morrendo e suas familias e muito dificil para as enfermeiras, devido ao intenso envolvimento. Buscam estrategias para lidar com a situacao e, diante do obito do neonato, apesar do sofrimento, manifestam o sentimento de dever cumprido. CONCLUSION: Enfrentar a morte e o luto aciona mecanismos que afloram referencias de vida, deparando-se com questoes dolorosas. Aprender a lidar com essas questoes e um desafio diario para os enfermeiros de UTIN. PMID- 27384287 TI - Analysis of Family Clinical, vision of service nurses. AB - OBJECTIVE: to know the practice of the Family Clinic in Cuiaba and its relationship with the precepts of the expanded clinic, from the perspective of the service nurses. METHOD: qualitative descriptive research, data collection with semi-structured interviews and results analyzed according to the method of thematic content analysis. RESULTS: for nurses working in the service, this assumes a differentiated and innovative proposal, which seeks to correlate with shared management in its three spheres. Although most do not know the Enlarged Clinic term in his speech cited its main principles and its tools. The greatest potential described were related to the Support Center for Health and popular participation, and as challenges, the lack of community health worker, the national health establishment registration and the difficulty of operation due to the profile of the professionals technical level arising from secondary care. CONCLUSIONS: The clinic has positive aspects that can contribute to the advancement of the profession, to train health professionals and an innovative primary care model. Therefore, it emphasizes the need for implementation of continuing education in order to realize its proposal, and further studies on site. OBJETIVO: conhecer a pratica da Clinica da Familia em Cuiaba e sua relacao com os preceitos da clinica ampliada, sob a perspectiva dos enfermeiros do servico. METODO: pesquisa descritiva qualitativa, coleta de dados com entrevista semi-estruturada e resultados analisados segundo o metodo de analise de conteudo do tipo tematica. RESULTADOS: para os enfermeiros atuantes no servico, este assume uma proposta diferenciada e inovadora, no qual busca se correlacionar com a gestao compartilhada em suas tres esferas. Apesar de a maioria nao conhecer o termo Clinica Ampliada em suas falas citaram seus principais preceitos e suas ferramentas. As maiores potencialidades descritas foram a relacao com o Nucleo de Apoio a Saude da Familia e a participacao popular, e como desafios, a falta de agente comunitario de saude, do cadastro nacional de estabelecimento de saude e a dificuldade de atuacao devido ao perfil dos profissionais de nivel tecnico advindos da atencao secundaria. CONCLUSAO: a clinica possui aspectos positivos que podem contribuir para o progresso da profissao, para a formacao de profissionais da saude e para um modelo de assistencia de nivel primario inovador. Logo, enfatiza-se a necessidade de implantacao da educacao permanente com o objetivo de concretizar sua proposta, alem de estudos posteriores no local. PMID- 27384288 TI - Psychological distress and community approach to the voice of the community health agent. AB - The user in psychological distress needs a service that provides a targeted assistance, that welcomes when required, acting as originator care device to the user on the network of health care. This study aimed to describe how people in psychological distress are perceived by the community in the voice of the community health worker. It is a qualitative research conducted with eighteen Community Health Agents, a Primary Care Unit Health (UAP) located in BE IV, in Fortaleza, Ceara. We used a semi-structured and individual interview. Data processing was due to the content analysis. Ethical and legal aspects on the advice No. 957,595. Through the speeches of ACS, it describes how the community perceives the person in psychic suffering and how it positions itself in the face of your everyday problems, as regards the rejection, prejudice, discrimination ne loss of identity. However it is emphasized that, because of being inserted in the community, the community health worker realizes more accurate way in which this social group is the person in mental distress. The rejection of the person who became ill is seen as a fairly common reaction, accompanied by prejudice and discrimination, marginalizing her from society. O usuario em sofrimento psiquico necessita de um servico que proporcione uma assistencia direcionada, que acolha no momento necessario, atuando como dispositivo ordenador do cuidado ao usuario na rede de atencao a saude. Objetivou-se descrever como as pessoas em sofrimento psiquico sao percebidas pela comunidade na voz do agente comunitario de saude. Trata-se de uma pesquisa qualitativa, realizada junto a dezoito Agentes Comunitarios de Saude, de uma Unidade de Atencao Primaria a Saude (UAPS) situada na SER IV, em Fortaleza-Ceara. Utilizou-se uma entrevista semiestruturada e individual. O processamento dos dados deu-se pela analise de conteudo. Aspectos eticos e legais sob parecer No 957.595. Atraves dos discursos dos ACS, descrevemos como a comunidade percebe a pessoa em sofrimento psiquico e como esta se posiciona frente as problematicas do seu cotidiano, no que se refere a rejeicao, preconceito, discriminacao e perda de identidade. Contudo destaca-se que, pelo fato de estar inserido na comunidade, o agente comunitario de saude percebe de forma mais apurada como tal grupo social trata a pessoa em sofrimento mental. A rejeicao da pessoa que adoeceu e observada como uma reacao bastante comum, acompanhada do preconceito e discriminacao, marginalizando-a da sociedade. PMID- 27384301 TI - Molecular breast tomosynthesis with scanning focus multi-pinhole cameras. AB - Planar molecular breast imaging (MBI) is rapidly gaining in popularity in diagnostic oncology. To add 3D capabilities, we introduce a novel molecular breast tomosynthesis (MBT) scanner concept based on multi-pinhole collimation. In our design, the patient lies prone with the pendant breast lightly compressed between transparent plates. Integrated webcams view the breast through these plates and allow the operator to designate the scan volume (e.g. a whole breast or a suspected region). The breast is then scanned by translating focusing multi pinhole plates and NaI(Tl) gamma detectors together in a sequence that optimizes count yield from the volume-of-interest. With simulations, we compared MBT with existing planar MBI. In a breast phantom containing different lesions, MBT improved tumour-to-background contrast-to-noise ratio (CNR) over planar MBI by 12% and 111% for 4.0 and 6.0 mm lesions respectively in case of whole breast scanning. For the same lesions, much larger CNR improvements of 92% and 241% over planar MBI were found in a scan that focused on a breast region containing several lesions. MBT resolved 3.0 mm rods in a Derenzo resolution phantom in the transverse plane compared to 2.5 mm rods distinguished by planar MBI. While planar MBI cannot provide depth information, MBT offered 4.0 mm depth resolution. Our simulations indicate that besides offering 3D localization of increased tracer uptake, multi-pinhole MBT can significantly increase tumour-to-background CNR compared to planar MBI. These properties could be promising for better estimating the position, extend and shape of lesions and distinguishing between single and multiple lesions. PMID- 27384289 TI - Synthesis and pharmacological evaluation of donepezil-based agents as new cholinesterase/monoamine oxidase inhibitors for the potential application against Alzheimer's disease. AB - In a continuing effort to develop multitargeted compounds as potential treatment agents against Alzheimer's disease (AD), a series of donepezil-like compounds were designed, synthesized and evaluated. In vitro studies showed that most of the designed compounds displayed potent inhibitory activities toward AChE, BuChE, MAO-B and MAO-A. Among them, w18 was a promising agent with balanced activities, which exhibited a moderate cholinesterase inhibition (IC50, 0.220 MUM for eeAChE; 1.23 MUM for eqBuChE; 0.454 MUM for hAChE) and an acceptable inhibitory activity against monoamine oxidases (IC50, 3.14 MUM for MAO-B; 13.4 MUM for MAO-A). Moreover, w18 could also be a metal-chelator, and able to cross the blood-brain barrier with low cell toxicity on PC12 cells. Taken together, these results suggested that w18 might be a promising multitargeted compound for AD treatment. PMID- 27384302 TI - Reduced Bone Density and Cortical Bone Indices in Female Adiponectin-Knockout Mice. AB - A positive association between fat and bone mass is maintained through a network of signaling molecules. Clinical studies found that the circulating levels of adiponectin, a peptide secreted from adipocytes, are inversely related to visceral fat mass and bone mineral density, and it has been suggested that adiponectin contributes to the coupling between fat and bone. Our study tested the hypothesis that adiponectin affects bone tissue by comparing the bone phenotype of wild-type and adiponectin-knockout (APN-KO) female mice between the ages of 8-37 weeks. Using a longitudinal study design, we determined body composition and bone density using dual energy x-ray absorptiometry. In parallel, groups of animals were killed at different ages and bone properties were analyzed by microcomputed tomography, dynamic histomorphometry, 3-point bending test, nanoindentation, and computational modelling. APN-KO mice had reduced body fat and decreased whole-skeleton bone mineral density. Microcomputed tomography analysis identified reduced cortical area fraction and average cortical thickness in APN-KO mice in all the age groups and reduced trabecular bone volume fraction only in young APN-KO mice. There were no major differences in bone strength and material properties between the 2 groups. Taken together, our results demonstrate a positive effect of adiponectin on bone geometry and density in our mouse model. Assuming adiponectin has similar effects in humans, the low circulating levels of adiponectin associated with increased fat mass are unlikely to contribute to the parallel increase in bone mass. Therefore, adiponectin does not appear to play a role in the coupling between fat and bone tissue. PMID- 27384304 TI - TGF-beta Induces Endometriotic Progression via a Noncanonical, KLF11-Mediated Mechanism. AB - Endometriosis, a chronic disease of heterogeneous etiopathology affects 10% of young women and is characterized by ectopic implantation of endometrial cells. Growth and spread of endometriosis lesions involves biological interplay between intrinsic lesion-driven and extrinsic host-responsive mechanisms. We propose a role for TGFbeta and its target transcription factor Kruppel-like factor 11 (KLF11) in mediating such mechanisms. Although TGFbeta, a pleiotropic cytokine implicated in endometriosis potentially, mediates its pathological phenotypes, KLF11 is associated with endocrine and reproductive tract diseases, specifically progression of endometriosis. In Ishikawa cells, TGFbeta1 treatment resulted in noncanonical SMAD-mediated transient up-regulation and sustained repression of KLF11. KLF11 recruits histone deacetylases to epigenetically repress multiple synthetic and metabolic cytochrome P450 (CYP) enzymes such as CYP3A4, which affects endometrial metabolism and pathophysiology. In contrast to KLF11, TGFbeta1 treatment caused transient repression and sustained activation of CYP3A4 expression. CYP3A4 increased endometrial cell proliferation and was also increased in human endometriosis lesions compared with eutopic endometrium. To determine whether dysregulation of TGFbeta/Klf11/Cyp3a signaling affected endometriotic progression, we treated wild-type control and Klf11-/- mice with a Tgfbeta type 1 receptor inhibitor (TGFbetaR1I) that inhibits Tgfbeta signaling upstream of the canonical Smad proteins or a combination of TGFbetaR1I and a histone acetyltransferase inhibitor that additionally inhibits Klf11 signaling. Disease progression and lesional Cyp3a expression was diminished in TGFbetaR1I treated animals and more so in animals treated synergistically with TGFbetaR1I and histone acetyltransferase inhibitor. TGFbeta and KLF11 thus mediate critical, translationally relevant host and lesion-driven responses that enable establishment and progression of endometriosis. PMID- 27384303 TI - The Methylcytosine Dioxygenase Ten-Eleven Translocase-2 (tet2) Enables Elevated GnRH Gene Expression and Maintenance of Male Reproductive Function. AB - Reproduction depends on the establishment and maintenance of elevated GnRH neurosecretion. The elevation of primate GnRH release is accompanied by epigenetic changes. Specifically, cytosine residues within the GnRH gene promoter are actively demethylated, whereas GnRH mRNA levels and peptide release rise. Whether active DNA demethylation has an impact on GnRH neuron development and consequently reproductive function remains unknown. In this study, we investigated whether ten-eleven translocation (tet) enzymes, which initiate the process of active DNA demethylation, influence neuronal function and reproduction. We found that tet2 expression increases with age in the developing mouse preoptic area-hypothalamus and is substantially higher in a mature (GT1-7) than an immature (GN11) GnRH cell line. GnRH mRNA levels and mean GnRH peptide release elevated after overexpression of tet2 in GN11 cells, whereas CRISPR/cas9 mediated knockdown of tet2 in GT1-7 cells led to a significant decline in GnRH expression. Manipulations of tet2 expression altered tet2 genome binding and histone 3 lysine 4 trimethylation abundance at the GnRH promoter. Mice with selective disruption of tet2 in GnRH neurons (GnRH-specific tet2 knockout mice) exhibited no sign of altered pubertal timing in either sex, although plasma LH levels were significantly lower, and fecundity was altered specifically in adult male GnRH-specific tet2 knockout animals, indicating that tet2 may participate in the maintenance GnRH neuronal function. Exposure to bisphenol A, an environmental contaminant that alters GnRH neuron activity, caused a shift in tet2 subcellular localization and a decrease in histone 3 lysine 4 trimethylation abundance at the GnRH promoter. Finally, evaluation of tet2 protein interactions in GT1-7 cells suggests that the influence of tet2 on neuronal function are not limited to nuclear mechanisms but could depend on mitochondrial function, and RNA metabolism. Together, these studies implicate tet2 in the maintenance of GnRH neuronal function and neuroendocrine control of male reproduction. PMID- 27384306 TI - The diagnostic accuracy of faecal calprotectin and small bowel capsule endoscopy and their correlation in suspected isolated small bowel Crohn's disease. AB - INTRODUCTION: Faecal calprotectin (FC) is less accurate at identifying inflammation in the small bowel than in the colon. Small bowel capsule endoscopy (SBCE) is a useful tool to detect small bowel inflammation. We investigated the diagnostic accuracy of FC and SBCE and their correlation in patients with suspected isolated small bowel Crohn's disease. PATIENTS AND METHODS: This was performed as a prospective single centre study including patients attending for SBCE with suspected small bowel Crohn's disease. Patient demographics, symptoms, medications and blood parameters were collected. Capsule endoscopy findings were analysed against calprotectin values, final diagnosis and blood parameters. RESULTS: A total of 146 patients were included (99 females and 47 males) with a mean age of 38+/-14 years. FC of more than 50 mg/kg was not significantly associated with clinically relevant capsule endoscopy findings (P=0.25), correlation coefficient was 0.11. Sensitivity, specificity, positive and negative predictive values for FC at a cut-off of more than 50 mg/kg were 88.9% [95% confidence interval (CI): 65.3-98.6], 25.0% (95% CI: 17.8-33.4), 14.3 (95% CI: 8.4-22.2) and 94.1% (95% CI: 80.3-99.3), respectively. A raised FC was not significantly associated with an elevated C-reactive protein or the presence of anaemia (P=0.19 and 0.10, respectively). CONCLUSION: FC performs modestly as a screening test to exclude small bowel inflammation. However, we recommend interpretation within the overall clinical context to avoid overlooking the infrequent patient with small bowel inflammation and a negative FC. PMID- 27384305 TI - Male 11beta-HSD1 Knockout Mice Fed Trans-Fats and Fructose Are Not Protected From Metabolic Syndrome or Nonalcoholic Fatty Liver Disease. AB - Nonalcoholic fatty liver disease (NAFLD) defines a spectrum of conditions from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis and is regarded as the hepatic manifestation of the metabolic syndrome. Glucocorticoids can promote steatosis by stimulating lipolysis within adipose tissue, free fatty acid delivery to liver and hepatic de novo lipogenesis. Glucocorticoids can be reactivated in liver through 11beta-hydroxysteroid dehydrogenase type 1 (11beta HSD1) enzyme activity. Inhibition of 11beta-HSD1 has been suggested as a potential treatment for NAFLD. To test this, male mice with global (11beta-HSD1 knockout [KO]) and liver-specific (LKO) 11beta-HSD1 loss of function were fed the American Lifestyle Induced Obesity Syndrome (ALIOS) diet, known to recapitulate the spectrum of NAFLD, and metabolic and liver phenotypes assessed. Body weight, muscle and adipose tissue masses, and parameters of glucose homeostasis showed that 11beta-HSD1KO and LKO mice were not protected from systemic metabolic disease. Evaluation of hepatic histology, triglyceride content, and blinded NAFLD activity score assessment indicated that levels of steatosis were similar between 11beta-HSD1KO, LKO, and control mice. Unexpectedly, histological analysis revealed significantly increased levels of immune foci present in livers of 11beta-HSD1KO but not LKO or control mice, suggestive of a transition to NASH. This was endorsed by elevated hepatic expression of key immune cell and inflammatory markers. These data indicate that 11beta-HSD1-deficient mice are not protected from metabolic disease or hepatosteatosis in the face of a NAFLD inducing diet. However, global deficiency of 11beta-HSD1 did increase markers of hepatic inflammation and suggests a critical role for 11beta-HSD1 in restraining the transition to NASH. PMID- 27384308 TI - Should we expect novel biomarkers of myocardial infarction? PMID- 27384307 TI - Ocular biometric parameters among 3-year-old Chinese children: testability, distribution and association with anthropometric parameters. AB - This survey was conducted to determine the testability, distribution and associations of ocular biometric parameters in Chinese preschool children. Ocular biometric examinations, including the axial length (AL) and corneal radius of curvature (CR), were conducted on 1,688 3-year-old subjects by using an IOLMaster in August 2015. Anthropometric parameters, including height and weight, were measured according to a standardized protocol, and body mass index (BMI) was calculated. The testability was 93.7% for the AL and 78.6% for the CR overall, and both measures improved with age. Girls performed slightly better in AL measurements (P = 0.08), and the difference in CR was statistically significant (P < 0.05). The AL distribution was normal in girls (P = 0.12), whereas it was not in boys (P < 0.05). For CR1, all subgroups presented normal distributions (P = 0.16 for boys; P = 0.20 for girls), but the distribution varied when the subgroups were combined (P < 0.05). CR2 presented a normal distribution (P = 0.11), whereas the AL/CR ratio was abnormal (P < 0.001). Boys exhibited a significantly longer AL, a greater CR and a greater AL/CR ratio than girls (all P < 0.001). PMID- 27384309 TI - Exercise simultaneously increases nasal patency and bronchial obstruction in asthmatic children. AB - We found that simultaneous post-exercise increase in nasal patency and bronchial obstruction occurs only in children with atopic asthma, but not in sensitized children without asthma. In healthy children, the increase in nasal patency is accompanied by bronchial dilatation. PMID- 27384310 TI - Prognostic Significance of Transverse Relaxation Rate (R2*) in Blood Oxygenation Level-Dependent Magnetic Resonance Imaging in Patients with Invasive Breast Cancer. AB - OBJECTIVE: To examine the relationship between magnetic resonance transverse relaxation rate (R2*) and prognostic factors. MATERIALS AND METHODS: A total of 159 women with invasive ductal carcinomas (IDCs) underwent breast magnetic resonance imaging (MRI) including blood oxygenation level-dependent (BOLD) sequence at 3 T. The distribution of the measured R2* values were analyzed, and the correlation between R2* and various prognostic factors (age, tumor size, histologic grade, lymphovascular invasion, and axillary lymph node status, as well as expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, p53, and Ki-67) were retrospectively assessed using patient medical records. RESULTS: The baseline R2* values of the IDCs were very heterogeneous with wide range among the patients. The mean R2* value was (32.8 +/ 14.0) Hz with a median of 29.3 Hz (range 13.5-109.4 Hz). In multivariate analysis, older age was associated with decreased R2* value (P = 0.011) and IDCs with p53-overexpression showed higher R2* values than those without p53 overexpression group (P = 0.031). Other prognostic factors were not significantly correlated with R2* value. CONCLUSION: In this study, R2* values were significantly correlated with age and expression of p53. Further studies are necessary to determine the prognostic value of BOLD-MRI. PMID- 27384313 TI - Intra-Abdominal Adhesions Make the Interpretation of Magnetic Resonance Enterography in Crohn's Disease More Difficult. AB - AIMS: The present study compares preoperative magnetic resonance enterography (MRE) accuracy in diagnosing stenoses, abscesses and fistulas to intraoperative findings in Crohn's disease patients, and determines whether discordance between these methods alter surgical plans. METHODS: Our study included 55 consecutive patients scheduled for elective surgery due to Crohn's disease in a single institution between January 2011 and May 2015, whose surgical findings were also compared to preoperative MREs. Data were retrospectively analyzed. RESULTS: Among these 55 patients, we found 80 stenoses, 5 abscesses and 18 fistulas during surgery. The MRE sensitivity, specificity and accuracy, respectively, reached 100, 77.8 and 96.4% for stenoses; 80.0, 90.0 and 89.1% for abscesses; and 77.8, 83.8 and 81.8% for fistulas. The operative plan was modified for 7 patients (12.7%) due to erroneous MRE diagnoses. No patient needed conversion or an unplanned stoma placement due to an incorrect diagnosis using MRE. The MRE diagnosis did not agree with the surgical findings for 36 lesions, 16 of which resulted from adhesions that explained the incorrect MRE diagnoses. CONCLUSIONS: Hence, while MRE is a useful diagnostic tool preoperatively in Crohn's disease patients, the presence of intra-abdominal adhesions may cause erroneous diagnosis through MRE. PMID- 27384314 TI - The Salience of Reward. PMID- 27384315 TI - Correction: Akap1 Deficiency Promotes Mitochondrial Aberrations and Exacerbates Cardiac Injury Following Permanent Coronary Ligation via Enhanced Mitophagy and Apoptosis. AB - [This corrects the article DOI: 10.1371/journal.pone.0154076.]. PMID- 27384316 TI - Estimation of brain network ictogenicity predicts outcome from epilepsy surgery. AB - Surgery is a valuable option for pharmacologically intractable epilepsy. However, significant post-operative improvements are not always attained. This is due in part to our incomplete understanding of the seizure generating (ictogenic) capabilities of brain networks. Here we introduce an in silico, model-based framework to study the effects of surgery within ictogenic brain networks. We find that factors conventionally determining the region of tissue to resect, such as the location of focal brain lesions or the presence of epileptiform rhythms, do not necessarily predict the best resection strategy. We validate our framework by analysing electrocorticogram (ECoG) recordings from patients who have undergone epilepsy surgery. We find that when post-operative outcome is good, model predictions for optimal strategies align better with the actual surgery undertaken than when post-operative outcome is poor. Crucially, this allows the prediction of optimal surgical strategies and the provision of quantitative prognoses for patients undergoing epilepsy surgery. PMID- 27384317 TI - Histological features of mixed neuroendocrine carcinoma and hepatocellular carcinoma in the liver: a case report and literature review. AB - Primary hepatic neuroendocrine carcinoma (NEC) is rare, and its origin, clinical features, diagnosis and treatment have not been clarified. Primary mixed NEC and hepatocellular carcinoma (HCC) is even rarer and is divided into either combined type or collision type. We report a patient with the combined type of mixed NEC and HCC. A 72-year-old male was diagnosed with HCC and underwent hepatectomy because of the presence of two tumors in his liver. Histological examination demonstrated that one of the tumors had both NEC and HCC components. The transitional zone was noted in the immunohistological examination, and the tumor was determined to be the combined type of primary mixed NEC and HCC. This was the first description of an HCC component being found in an NEC-dominant area in a primary mixed NEC and HCC tumor. Three weeks after hepatectomy, an abdominal computed tomography scan showed extensive regional and para-aortic lymphadenopathy, and early relapse was suspected in the patient. The patient died 3 months after the operation despite treatment with combination chemotherapy. This report describes an unfavorable case and summarizes all the primary mixed NEC and HCC tumor cases that have been previously reported. PMID- 27384318 TI - Kefir reduces insulin resistance and inflammatory cytokine expression in an animal model of metabolic syndrome. AB - There is growing evidence that kefir can be a promising tool in decreasing the risk of many diseases, including metabolic syndrome (MetS). The aim of the present study was to evaluate the effect of kefir supplementation in the diet of Spontaneously Hypertensive Rats (SHR) in which MetS was induced with monosodium glutamate (MSG), and to determine its effect on metabolic parameters, inflammatory and oxidation marker expression and glycemic index control. Thirty animals were used in this experiment. For the induction of MetS, twenty two-day old male SHR received five consecutive intradermal injections of MSG. For the Negative Control, ten newborn male SHR received intradermal injections of saline solution (0.9% saline solution). After weaning, animals received standard diet and water ad libitum until reaching 3 months old, for the development of MetS. They were then divided into three groups (n = 10): negative control (NC, 1 mL saline solution per day), positive control (PC, 1 mL saline solution per day) and the Kefir group (1 mL kefir per day). Feeding was carried out by gavage for 10 weeks and the animals received standard food and water ad libitum. Obesity, insulin resistance, pro- and anti-inflammatory markers, and the histology of pancreatic and adipose tissues were among the main variables evaluated. Compared to the PC group, kefir supplementation reduced plasma triglycerides, liver lipids, liver triglycerides, insulin resistance, fasting glucose, fasting insulin, thoracic circumference, abdominal circumference, products of lipid oxidation, pro-inflammatory cytokine expression (IL-1beta) and increased anti inflammatory cytokine expression (IL-10). The present findings indicate that kefir has the potential to benefit the management of MetS. PMID- 27384319 TI - Desirable Characteristics of Hepatitis C Treatment Regimens: A Review of What We Have and What We Need. AB - There have been dramatic advancements in the treatment of chronic hepatitis C (HCV) infection. This is largely due to the approval of several direct-acting antiviral agents (DAAs) from a variety of medication classes with novel mechanisms of action. These therapies are a welcomed advancement given their improved efficacy and tolerability compared to pegylated interferon and ribavirin (RBV)-based regimens. These convenient, all-oral regimens treat a variety of genotypes and often offer high cure rates in a variety of HCV-infected populations. While there are several benefits associated with these therapies, there are also notable shortcomings. Shortcomings include diminished response or need for adjunctive RBV in difficult-to-treat populations (decompensated cirrhosis, active substance abuse patients, advanced kidney disease, etc.), activity against select genotypes, substantial drug-drug interaction potential, and high cost. Therefore, while current DAA-based therapies have several favorable attributes, each also has its limitations. The purpose of this review is to (1) identify the characteristics of an ideal HCV treatment regimen, (2) describe desirable features of existing regimens, (3) summarize limitations of existing regimens, and (4) introduce promising emerging therapies. This manuscript will serve as a guide for evaluating the caliber of future HCV treatment regimens. PMID- 27384320 TI - Highly Stretchable and Sensitive Strain Sensor Based on Facilely Prepared Three Dimensional Graphene Foam Composite. AB - Wearable strain sensors with excellent stretchability and sensitivity have emerged as a very promising field which could be used for human motion detection and biomechanical systems, etc. Three-dimensional (3D) graphene foam (GF) has been reported before for high-performance strain sensors, however, some problems such as high cost preparation, low sensitivity, and stretchability still remain. In this paper, we report a highly stretchable and sensitive strain sensor based on 3D GF and polydimethylsiloxane (PDMS) composite. The GF is prepared by assembly process from graphene oxide via a facile and scalable method and possesses excellent mechanical property which facilitates the infiltration of PDMS prepolymer into the graphene framework. The as-prepared strain sensor can be stretched as high as 30% of its original length and the gauge factor of this sensor is as high as 98.66 under 5% of applied strain. Moreover, the strain sensor shows long-term stability in 200 cycles of stretching-relaxing. Implementation of the device for monitoring the bending of elbow and finger results in reproducibility and various responses in the form of resistance change. Thus, the developed strain sensors exhibit great application potential in fields of biomechanical systems and human-interactive applications. PMID- 27384321 TI - Distinct MicroRNA Expression Signatures of Porcine Induced Pluripotent Stem Cells under Mouse and Human ESC Culture Conditions. AB - It is well known that microRNAs play a very important role in regulating reprogramming, pluripotency and cell fate decisions. Porcine induced pluripotent stem cells (piPSCs) are now available for studying the pluripotent regulation network in pigs. Two types of piPSCs have been derived from human and mouse embryonic stem cell (ESC) culture conditions: hpiPSCs and mpiPSCs, respectively. The hpiPSCs were morphologically similar to human ESCs, and the mpiPSCs resembled mouse ESCs. However, our current understanding of the role of microRNAs in the development of piPSCs is still very limited. Here, we performed small RNA sequencing to profile the miRNA expression in porcine fibroblasts (pEFs), hpiPSCs and mpiPSCs. There were 22 differential expressed (DE) miRNAs down-regulated in both types of piPSCs compared with pEFs, such as ssc-miR-145-5p and ssc-miR-98. There were 27 DE miRNAs up-regulated in both types of piPSCs compared with pEFs. Among these up-regulated DE miRNAs in piPSCs, ssc-miR-217, ssc-miR-216, ssc-miR 142-5p, ssc-miR-182, ssc-miR-183 and ssc-miR-96-5p have much higher expression levels in mpiPSCs, while ssc-miR-106a, ssc-miR-363, ssc-miR-146b, ssc-miR-195, ssc-miR-497, ssc-miR-935 and ssc-miR-20b highly expressed in hpiPSCs. Quantitative stem-loop RT-PCR was performed to confirm selected DE miRNAs expression levels. The results were consistent with small RNA sequencing. Different expression patterns were observed for key miRNA clusters, such as the miR-17-92 cluster, the let-7 family, the miR-106a-363 cluster and the miR-182-183 cluster, in the mpiPSCs and hpiPSCs. Novel miRNAs were also predicted in this study, including a putative porcine miR-302 cluster: ssc_38503, ssc_38503 and ssc_38501 (which resemble human miR-302a and miR-302b) found in both types of piPSCs. The miR-106a-363 cluster and putative miR-302 cluster increased the reprogramming efficiency of pEFs. The study revealed significant differences in the miRNA signatures of hpiPSCs and mpiPSCs under different pluripotent states that were derived from different culture conditions. These differentially expressed miRNAs may play important roles in pluripotent regulation in pigs, and this information will facilitate the understanding of the mechanism of pluripotency in pigs. PMID- 27384323 TI - GMC review of fitness to practise procedures is complete. PMID- 27384322 TI - Ogg1-Dependent DNA Repair Regulates NLRP3 Inflammasome and Prevents Atherosclerosis. AB - RATIONALE: Activation of NLRP3 (nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3) inflammasome-mediating interleukin (IL)-1beta secretion has emerged as an important component of inflammatory processes in atherosclerosis. Mitochondrial DNA (mtDNA) damage is detrimental in atherosclerosis, and mitochondria are central regulators of the nucleotide binding domain and leucine-rich repeat pyrin domain containing 3 inflammasome. Human atherosclerotic plaques express increased mtDNA damage. The major DNA glycosylase, 8-oxoguanine glycosylase (OGG1), is responsible for removing the most abundant form of oxidative DNA damage. OBJECTIVE: To test the role of OGG1 in the development of atherosclerosis in mouse. METHODS AND RESULTS: We observed that Ogg1 expression decreases over time in atherosclerotic lesion macrophages of low-density lipoprotein receptor (Ldlr) knockout mice fed a Western diet. Ogg1(-/ )Ldlr(-/-) mice fed a Western diet resulted in an increase in plaque size and lipid content. We found increased oxidized mtDNA, inflammasome activation, and apoptosis in atherosclerotic lesions and also higher serum IL-1beta and IL-18 in Ogg1(-/-)Ldlr(-/-) mice than in Ldlr(-/-). Transplantation with Ogg1(-/-) bone marrow into Ldlr(-/-) mice led to larger atherosclerotic lesions and increased IL 1beta production. However, transplantation of Ogg1(-/-)Nlrp3(-/-) bone marrow reversed the Ogg1(-/-) phenotype of increased plaque size. Ogg1(-/-) macrophages showed increased oxidized mtDNA and had greater amounts of cytosolic mtDNA and cytochrome c, increased apoptosis, and more IL-1beta secretion. Finally, we found that proatherogenic miR-33 can directly inhibit human OGG1 expression and indirectly suppress both mouse and human OGG1 via AMP-activated protein kinase. CONCLUSIONS: OGG1 plays a protective role in atherogenesis by preventing excessive inflammasome activation. Our study provides insight into a new target for therapeutic intervention based on a link between oxidative mtDNA damage, OGG1, and atherosclerosis via NLRP3 inflammasome. PMID- 27384324 TI - Molecular evolution of the capsid gene in human norovirus genogroup II. AB - Capsid protein of norovirus genogroup II (GII) plays crucial roles in host infection. Although studies on capsid gene evolution have been conducted for a few genotypes of norovirus, the molecular evolution of norovirus GII is not well understood. Here we report the molecular evolution of all GII genotypes, using various bioinformatics techniques. The time-scaled phylogenetic tree showed that the present GII strains diverged from GIV around 1630CE at a high evolutionary rate (around 10(-3) substitutions/site/year), resulting in three lineages. The GII capsid gene had large pairwise distances (maximum > 0.39). The effective population sizes of the present GII strains were large (>10(2)) for about 400 years. Positive (20) and negative (over 450) selection sites were estimated. Moreover, some linear and conformational B-cell epitopes were found in the deduced GII capsid protein. These results suggested that norovirus GII strains rapidly evolved with high divergence and adaptation to humans. PMID- 27384325 TI - Exome sequencing in pooled DNA samples to identify maternal pre-eclampsia risk variants. AB - Pre-eclampsia is a common pregnancy disorder that is a major cause for maternal and perinatal mortality and morbidity. Variants predisposing to pre-eclampsia might be under negative evolutionary selection that is likely to keep their population frequencies low. We exome sequenced samples from a hundred Finnish pre eclamptic women in pools of ten to screen for low-frequency, large-effect risk variants for pre-eclampsia. After filtering and additional genotyping steps, we selected 28 low-frequency missense, nonsense and splice site variants that were enriched in the pre-eclampsia pools compared to reference data, and genotyped the variants in 1353 pre-eclamptic and 699 non-pre-eclamptic women to test the association of them with pre-eclampsia and quantitative traits relevant for the disease. Genotypes from the SISu project (n = 6118 exome sequenced Finnish samples) were included in the binary trait association analysis as a population reference to increase statistical power. In these analyses, none of the variants tested reached genome-wide significance. In conclusion, the genetic risk for pre eclampsia is likely complex even in a population isolate like Finland, and larger sample sizes will be necessary to detect risk variants. PMID- 27384327 TI - Associations of Guideline Recommended Medications for Acute Coronary Syndromes With Fall-Related Hospitalizations and Cardiovascular Events in Older Women With Ischemic Heart Disease. AB - BACKGROUND: Guidelines for acute coronary syndrome recommend statins, beta blockers, angiotensin-converting-enzyme inhibitors or renin-angiotensin system blockers, and antiplatelet agents for the secondary prevention of cardiovascular events. The aim was to examine associations between guideline recommended medications and fall-related hospitalizations and cardiovascular events in robust and frail older women. METHODS: 2002-2011 surveys from the Australian Longitudinal Study on Women's Health linked with administrative hospital, pharmaceutical and death registry data (2003-mid-2011) were used. Eight hundred eighty-five women (82.7+/-2.7 years, range 76-90) had prior admission for ischemic heart disease and >=1 claims for any of the four medication classes. Four hundred thirteen (46.7%) were robust and 472 (53.3%) were frail. Fall related admissions; cardiovascular event-related admissions or death; and cardiovascular death were recorded. Associations between each of the exposures and outcomes were analyzed using survival analyses with noncardiovascular death as a competing risk. RESULTS: There were 192 fall-related admissions and 314 cardiovascular events including 82 deaths. Using four recommended classes (compared to using one) was associated with increased risks of fall-related admissions (hazard ratio [HR] = 2.57, 95% confidence interval [CI] = 1.24-5.33), but not with cardiovascular events (HR = 1.41, CI = 0.97-2.05) or cardiovascular death (HR = 0.68, CI = 0.35-1.34). Associations for fall-related admissions were stronger in frail participants (HR = 5.46, CI = 1.34-22.30) than robust (HR = 1.37, CI = 0.48-3.95). CONCLUSIONS: In older women with ischemic heart disease, the combination of the four recommended medication classes was associated with increased risk of falls, particularly among frail women, with no statistically significant gain in cardiovascular health. The risks of falls and consequential morbidity in women over 75 needs consideration when prescribing medications after myocardial infarction. PMID- 27384326 TI - Short-Term Exposure to Urban Air Pollution and Influences on Placental Vascularization Indexes. AB - BACKGROUND: It has been widely demonstrated that air pollution can affect human health and that certain pollutant gases lead to adverse obstetric outcomes, such as preeclampsia and fetal growth restriction. OBJECTIVES: We evaluated the influence of individual maternal exposure to air pollution on placental volume and vascularization evaluated in the first trimester of pregnancy. METHODS: This was a cross-sectional study on low-risk pregnant women living in Sao Paulo, Brazil. The women carried passive personal NO2 and O3 monitors in the week preceding evaluation. We employed the virtual organ computer-aided analysis (VOCAL) technique using three-dimensional power Doppler ultrasound to evaluate placental volume and placental vascular indexes [vascularization index (VI), flow index (FI), and vascularization flow index (VFI)]. We analyzed the influence of pollutant levels on log-transformed placental vascularization and volume using multiple regression models. RESULTS: We evaluated 229 patients. Increased NO2 levels had a significant negative association with log of VI (p = 0.020 and beta = -0.153) and VFI (p = 0.024 and beta = -0.151). NO2 and O3 had no influence on the log of placental volume or FI. CONCLUSIONS: NO2, an estimator of primary air pollutants, was significantly associated with diminished VI and VFI in the first trimester of pregnancy. PMID- 27384328 TI - Vibrating Platform Training Improves Respiratory Muscle Strength, Quality of Life, and Inspiratory Capacity in the Elderly Adults: A Randomized Controlled Trial. AB - Background: Aging affects respiratory strength that could cause reduction in functional capacity and quality of life, playing a fundamental role in healthy aging and survival. To prevent these declines, the whole body vibration (WBV) has been proposed to increase strength and functional capacity. The aim of the study was to evaluate the effects of WBV on respiratory muscle strength, thoracoabdominal ventilation, and quality of life in the elderly adults. Methods: This study was a controlled, randomized double-blind clinical trial. The study included 28 elderly adults randomized into three groups: Resistance (n = 9), WBV (n = 9), or WBV + resistance exercises (n = 10), performing training, sham, or double training for 3 months, twice per week. The variables of the study were as follows: maximal inspiratory and expiratory pressures (MIP and MEP), distribution of thoracoabdominal volumes variation in optoelectronic plethysmography (pulmonary rib cage-VRCp, abdominal rib cage-VRCa, and abdomen-VAB), and quality of life. Results: After training, WBV and WBV + resistance groups increased MIP and MEP (p < .001). During inspiratory capacity maneuver, WBV groups had incremental increases in chest wall total volume (p < .001), showing a rise in pulmonary rib cage (p = .03) and abdominal rib cage (p = .04). Furthermore, WBV groups improved SF-36 scores in functional capacity, physical aspects, energy, pain, and general heath domains. Conclusions: The WBV is a training that could improve respiratory muscle strength and quality of life and promote different ventilatory strategies in chest wall and thoracoabdominal compartments in healthy elderly adults. PMID- 27384329 TI - Prefectural difference in spontaneous intracerebral hemorrhage incidence in Japan analyzed with publically accessible diagnosis procedure combination data: possibilities and limitations. AB - OBJECTIVES: Annually reported, publically accessible Diagnosis Procedure Combination (DPC) data from the Japanese government is a part of the total DPC database of the Japanese medical reimbursement system for hospitalization. Although medical issues can be evaluated with these data promptly, the applicability of these data in epidemiological analyses has not been assessed. METHODS: We performed analyses using only statistical indices reported on the a government website. As a preliminary step, the prefectural consistency of spontaneous intracerebral hemorrhage (sICH) was examined with prefectural mortality over 20 years. Then the prefectural incidence of sICH for four years was calculated, utilizing publically accessible DPC data. To determine its reliability, the consistency was examined, and correlations were analyzed with three prefectural factors expected to have an effect: the elderly rate, mortality due to sICH, and the non-DPC bed rate. In addition, a comparison model between prefectures with this method was developed by analyzing other prefecture-specific factors. RESULTS: Prefectural mortality due to sICH and prefectural sICH incidence in the DPC database were both consistent over the years. Prefectural sICH incidence had a constant positive correlation with the elderly rate, a partial correlation with mortality due to sICH, but no correlation with the non DPC bed rate, which is one of the major biases when utilizing the DPC database. In the comparison model, the factors of low income and alcohol consumption showed increased sICH incidence. CONCLUSIONS: Although careful attention to its limitations is required, publically accessible DPC data will provide insights into epidemiological issues. PMID- 27384331 TI - Atmospheric Physical Chemistry. PMID- 27384330 TI - Executive Function, Visual Attention and the Cocktail Party Problem in Musicians and Non-Musicians. AB - The goal of this study was to investigate how cognitive factors influence performance in a multi-talker, "cocktail-party" like environment in musicians and non-musicians. This was achieved by relating performance in a spatial hearing task to cognitive processing abilities assessed using measures of executive function (EF) and visual attention in musicians and non-musicians. For the spatial hearing task, a speech target was presented simultaneously with two intelligible speech maskers that were either colocated with the target (0 degrees azimuth) or were symmetrically separated from the target in azimuth (at +/-15 degrees ). EF assessment included measures of cognitive flexibility, inhibition control and auditory working memory. Selective attention was assessed in the visual domain using a multiple object tracking task (MOT). For the MOT task, the observers were required to track target dots (n = 1,2,3,4,5) in the presence of interfering distractor dots. Musicians performed significantly better than non musicians in the spatial hearing task. For the EF measures, musicians showed better performance on measures of auditory working memory compared to non musicians. Furthermore, across all individuals, a significant correlation was observed between performance on the spatial hearing task and measures of auditory working memory. This result suggests that individual differences in performance in a cocktail party-like environment may depend in part on cognitive factors such as auditory working memory. Performance in the MOT task did not differ between groups. However, across all individuals, a significant correlation was found between performance in the MOT and spatial hearing tasks. A stepwise multiple regression analysis revealed that musicianship and performance on the MOT task significantly predicted performance on the spatial hearing task. Overall, these findings confirm the relationship between musicianship and cognitive factors including domain-general selective attention and working memory in solving the "cocktail party problem". PMID- 27384332 TI - Can an enhanced thin-slice computed tomography delineate the right adrenal vein and improve the success rate? AB - PURPOSE: To evaluate the usefulness of enhanced thin-slice computed tomography (TSCT) for delineating the right adrenal vein (RAV) anatomy before adrenal vein sampling (AVS). MATERIALS AND METHODS: A total of 151 consecutive AVSs with CT during angiography (interventional CT) were included. Of them, TSCT was performed before AVS for 72 patients. Successful RAV cannulation was confirmed using cortisol measurement. The RAV on TSCT was classified as certain, probable, or unidentified, and cases with certain or probable RAV identification were classified as useful. In the cases where AVS was successful, the anatomical features of the presumed RAV from the useful TSCT, including the position along the inferior vena cava, vertebral level, and distance from the upper pole of the right kidney, were compared with the RAV features identified on interventional CT. Estimated successful cannulation rates before interventional CT were compared between patients with and without useful TSCT. RESULTS: In total, 66 TSCTs were classified as useful. The anatomical features identified on TSCT were significantly correlated with those on interventional CT. The estimated successful cannulation rates for cases with and without useful TSCT were 92.4 and 82.4 %, respectively. CONCLUSIONS: TSCT clearly shows the anatomical features of the RAV, facilitating accurate sampling and increasing the success rate. PMID- 27384333 TI - [Grading of soft tissue and bone sarcomas]. AB - Malignancy grading is an essential element in the classification of sarcomas. It correlates with the prognosis of the disease and the risk of metastasis. This article presents the grading schemes for soft tissue, bone and pediatric sarcomas. It summarizes the histological criteria of the Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system and the Pediatric Oncology Group as well as the grading of bone tumors by the College of American Pathologists (CAP). Furthermore, the potential relevance of gene expression signatures, the complexity index in sarcoma (CINSARC) and single genetic alterations (p53, MDM2, p16, SWI/SNF, EWSR1 fusions and PAX3/PAX7-FOXO1 fusions) for the prognosis of sarcomas are discussed. PMID- 27384334 TI - [Clinical and epidemiological cancer registration in Germany]. AB - OBJECTIVE: Function and funding of detailed clinical cancer registries (CCRs) is defined by German Social Code Book V (SGB V) and shall be implemented by the end of 2017. CONTENT: Cancer registration according to regionally defined catchment areas, feedback of results and quality assurance are the basis which determines principles of operation and use of data. Each clinical department delivers only its own findings and therapy, while compilation by the clinical cancer registry describes the patients' way through the regional network of medical care. In this way, oncological centers are not burdened by troublesome documentation of data which originate from other clinics. CONCLUSION: After successful implementation of CCRs, interested physicians and clinics are able to spend time for analysis and use of meaningful data with the objective of improving quality of care within the region, implementing innovative therapies and presenting their results, and generating new hypotheses to stimulate research. PMID- 27384336 TI - Surveys on Reporting Guideline Usage in Dental Journals. AB - The objectives of this study were 1) to find out if and how authors and peer reviewers for dental journals are encouraged to use reporting guidelines (RGs); 2) to identify factors related to RG endorsement; and 3) to assess the knowledge, opinions, and future plans of dental journal editors in chief (EICs) on RGs. A total of 109 peer-reviewed and original research-oriented dental journals that were indexed in the MEDLINE and/or SCIE database in 2015 were included. The "instructions to authors" and "instructions to reviewers" of these journals were identified and retrieved from journals' official websites. Any mention of RGs or other related policies were sought and extracted. In addition, an anonymous survey of the EICs of the included journals was conducted with a validated questionnaire. All 109 journals provided "instructions to authors," among which 55 (50.5%) mentioned RGs. Only the CONSORT (45.0%), PRISMA (13.8%), and STROBE (12.8%) guidelines were mentioned by >10% of the included journals. Statistical analyses suggest that RGs were more frequently mentioned by SCIE-indexed journals (P < 0.001), higher-impact journals (P = 0.002), and journals that endorsed the ICMJE recommendations (P < 0.001). "Instructions to reviewers" were available online for only 9 journals (8.3%), 3 of which mentioned RGs. For the EIC survey, the response rate was 32.1% (35 of 109). Twenty-six editors (74.3%) stated that they knew what RGs were before receiving our questionnaire. Twenty-four editors (68.6%) believed that RGs should be adopted by all refereed dental journals where appropriate. RGs are important tools for enhancing research reporting and reducing avoidable research waste, but currently they are not widely endorsed by dental journals. Joint efforts by all stakeholders to further promote RG usage in dentistry are needed. PMID- 27384335 TI - DPSCs from Inflamed Pulp Modulate Macrophage Function via the TNF-alpha/IDO Axis. AB - Human dental pulp stem cells (DPSCs) can be isolated from inflamed pulp derived from carious teeth with symptomatic irreversible pulpitis (I-DPSCs), which possess stemness and multidifferentiation potentials similar to DPSCs from healthy pulp. Since macrophages-essential cell players of the pulpal innate immunity-can regulate pulpal inflammation and repair, the authors investigated the immunomodulatory effects of DPSCs/I-DPSCs on macrophage functions and their underlying mechanisms. Similar to DPSCs, I-DPSCs were capable of colony-forming efficiency and adipogenic and osteo/dentinogenic differentiation under in vitro induction conditions. I-DPSCs also expressed a similar phenotypic profile of mesenchymal stem cell markers, except a relatively higher level of CD146 as compared with DPSCs. Coculture of DPSCs or I-DPSCs with differentiated THP-1 cells, the human monocyte cell line, markedly suppressed tumor necrosis factor alpha (TNF-alpha) secretion in response to stimulation with lipopolysaccharides (LPS) and/or nigericin. However, unlike TNF-alpha, the secreted level of interleukin 1beta was not affected by coculture with DPSCs or I-DPSCs. Furthermore, DPSC/I-DPSC-mediated inhibition of TNF-alpha secretion by macrophages was abolished by pretreatment with 1-methyl-D-tryptophan, a specific inhibitor of indoleamine-pyrrole 2,3-dioxygenase (IDO), but not by NSC-398, a specific inhibitor of COX-2, suggesting IDO as a mediator. Interestingly, IDO expression was significantly augmented in macrophages and mesenchymal stromal cells in inflamed human pulp tissues. Collectively, these findings show that I DPSCs, similar to DPSCs, possess stem cell properties and suppress macrophage functions via the TNF-alpha/IDO axis, thereby providing a physiologically relevant context for their innate immunomodulatory activity in the dental pulp and their capability for pulp repair. PMID- 27384337 TI - Site specific N-glycan profiling of NeuAc(alpha2-6)-Gal/GalNAc-binding bark Sambucus nigra agglutinin using LC-MSn revealed differential glycosylation. AB - The bark of Sambucus nigra contains a complex mixture of glycoproteins that are characterized as chimeric lectins known as type II ribosome inactivating proteins and holo lectins. These type II ribosome inactivating proteins possess RNA N glycosidase activity in subunit A and lectin activity associated with subunit B exhibiting distinct sugar specificities to NeuAc(alpha2-6)-Gal/GalNAc and Gal/GalNAc. In the present study we have determined the N-glycosylation pattern of type II ribosome inactivating protein specific to NeuAc(alpha2-6)-Gal/GalNAc (Sambucus nigra agglutinin I) by subjecting it to digestion with multiple proteases. The resulting mixture of peptides and N-glycopeptides were analyzed on liquid chromatography coupled to electro spray ionization-iontrap mass spectrometry in MSn mode. MS2 of precursor ions was carried out using CID which provided information on glycan sequence. In subsequent MS3 of Y1/Y1alpha ions (peptide + HexNAc)+n of corresponding N-glycopeptides, resulted in the fragmentation of peptide backbone confirming the site of attachment. We observed microheterogeneity in each glycan occupied site with subunit A possessing four N glycans out of six sites with complex and paucimannose types while subunit B comprises occupancy of two sites with a paucimannose and a high mannose type. The differential N-glycosylation of subunits in SNA is discussed in the context of other type II RIPs glycans. PMID- 27384338 TI - Hydroregulation in a tropical dry-skinned ectotherm. AB - While temperature effects on species' vulnerability to climate change are well studied, desiccation effects receive comparatively little attention. In addition, we poorly understand the capacity of ectotherms, and especially reptiles, to control water loss rates behaviourally by selecting suitable microhabitats. This study examined water loss rates and behavioural hydroregulation in the tropical rainforest skink Carlia rubrigularis to assess whether this dry-skinned ectotherm actively avoids desiccation and whether trade-offs occur between desiccation avoidance and selection of optimal temperatures, as previously shown in amphibians. Higher temperatures elicited humid refuge choice despite placing individuals in suboptimal thermal conditions, as indicated by preferred substrate temperatures. This finding emphasizes the importance of water loss even for taxa traditionally assumed to be highly desiccation resistant, and highlights this factor's potential influence on vulnerability to climate change by limiting activity times or by restricting individuals to thermally suboptimal microhabitats. PMID- 27384339 TI - Stable isotope physiology of stem succulents across a broad range of volume-to surface area ratio. AB - Volume-to-surface area ratio (V:S) across stem succulent taxa varies by almost two orders of magnitude. The broad range in V:S of cacti and other succulent species likely has considerable importance for adaptation since stem volume determines the storage capacity of water, carbon and nutrients and stem surface area is directly related to whole-stem photosynthetic capacity. We examined the intrinsic physiological tradeoffs across diverse stem morphologies in three divergent evolutionary groups where stem succulence is common: Cactoideae, Opuntioideae (Cactaceae) and Euphorbiaceae. We predicted that variation in physiological response to environmental conditions would be (1) constrained by stem V:S, and (2) detectable in the stable isotope ratios of plant tissues. Stable isotope ratios were measured in the spines/prickles of 62 stem-succulent species occurring in a common garden setting in Phoenix, AZ, USA. Biomass delta(13)C, delta(2)H and delta(18)O increased with V:S in Cactoideae only, possibly reflecting various levels of Crassulacean acid metabolism (CAM) strength in the other lineages. Within Cactoideae-group with the highest CAM strength and largest range in V:S-delta(13)C and delta(18)O increased 2.2 and 11.5 0/00, respectively, with a 22-fold increase in V:S. Both delta(13)C and V:S decreased with species climate-niche estimates of precipitation, indicating that stem morphology and physiology in Cactoideae may be constrained by available moisture. Taken together, these data suggest that physiological tradeoffs associated with stem V:S are detectable across broad evolutionary groups despite differences in CAM strength. PMID- 27384340 TI - Patent foramen ovale and cryptogenic stroke: from studies to clinical practice: Position paper of the Italian Chapter, International Society Cardiovascular Ultrasound. AB - BACKGROUND: Over the last two decades the interest on patent foramen ovale (PFO) as a cause of cardioembolism in cryptogenic stroke has tremendously increased, thanks to the availability of better techniques to diagnose cardiac right-to-left shunt by ultrasounds and of percutaneous means of PFO treatment with interventional techniques. Many studies have been published that have attempted to define diagnostic methodology, prognosis, and optimal treatment (pharmacological or percutaneous closure) of PFO patients with cryptogenic stroke. Unfortunately, even today, definitive evidence is still lacking, and clinical management is not consistent among cardiologists. AIMS: This review aims to evaluate the role of PFO in cryptogenic stroke, the diagnostic accuracy of transcranial Doppler, contrast transthoracic and transesophageal echocardiography in the diagnosis of left-fright shunt and PFO; and discuss the indications to medical treatment and percutaneous closure of PFO. METHODS: All studies published in the literature on PFO and cryptogenic stroke are considered and discussed. RESULTS: We define an appropriate diagnostic and clinical management of PFO patients with cryptogenic stroke. CONCLUSION: After many years of interest on PFO and many concluded studies, there are still no definitive data. However, we are on good track for an appropriate management of PFO patients and cryptogenic stroke. PMID- 27384341 TI - Understanding the Chronology and Occupation Dynamics of Oversized Pit Houses in the Southern Brazilian Highlands. AB - A long held view about the occupation of southern proto-Je pit house villages of the southern Brazilian highlands is that these sites represent cycles of long term abandonment and reoccupation. However, this assumption is based on an insufficient number of radiocarbon dates for individual pit houses. To address this problem, we conducted a programme of comprehensive AMS radiocarbon dating and Bayesian modelling at the deeply stratified oversized pit House 1, Baggio I site (Cal. A.D. 1395-1650), Campo Belo do Sul, Santa Catarina state, Brazil. The stratigraphy of House 1 revealed an unparalleled sequence of twelve well preserved floors evidencing a major change in occupation dynamics including five completely burnt collapsed roofs. The results of the radiocarbon dating allowed us to understand for the first time the occupation dynamics of an oversized pit house in the southern Brazilian highlands. The Bayesian model demonstrates that House 1 was occupied for over two centuries with no evidence of major periods of abandonment, calling into question previous models of long-term abandonment. In addition, the House 1 sequence allowed us to tie transformations in ceramic style and lithic technology to an absolute chronology. Finally, we can provide new evidence that the emergence of oversized domestic structures is a relatively recent phenomenon among the southern proto-Je. As monumental pit houses start to be built, small pit houses continue to be inhabited, evidencing emerging disparities in domestic architecture after AD 1000. Our research shows the importance of programmes of intensive dating of individual structures to understand occupation dynamics and site permanence, and challenges long held assumptions that the southern Brazilian highlands were home to marginal cultures in the context of lowland South America. PMID- 27384342 TI - Association of metals (Cd, Fe, As, Ni, Cu, Zn and Mn) with cigarette butts in northern part of the Persian Gulf. AB - Cigarette butts are the most common form of litter in the marine environment and represent potential point sources for environmental contamination. The metals leached from cigarette butts have not been studied well in the marine environment. In this study, the levels of metals (Cd, Fe, As, Ni, Cu, Zn and Mn) in cigarette butts were monitored at nine stations along the northern part of the Persian Gulf in Bushehr coastal areas in summer 2015 with a sampling time interval of 10 days. The Cd, Fe, As, Ni, Cu, Zn and Mn contents of cigarette butts were found to vary widely between 0.16 and 0.67 MUg/g, 79.01 and 244.97 MUg/g, 0.12 and 0.48 MUg/g, 1.13 and 3.27 MUg/g, 4.29 and 12.29 MUg/g, 6.39 and 21.17 MUg/g, and 38.29 and 123.1 MUg/g, respectively. A Wilcoxon signed rank test showed that there were no significant differences between the Cd, Fe, As, Ni, Cu, Zn and Mn contents of cigarette butts at different sampling times. Considering the estimated number of cigarette butts littered annually, the results of this study indicated that considerable metals including Cd, Fe, As, Ni, Cu, Zn and Mn may enter the marine environment each year from cigarette litter alone. PMID- 27384343 TI - Biofilm adaptation to iron availability in the presence of biotite and consequences for chemical weathering. AB - Bacteria in nature often live within biofilms, exopolymeric matrices that provide a favorable environment that can differ markedly from their surroundings. Biofilms have been found growing on mineral surfaces and are expected to play a role in weathering those surfaces, but a clear understanding of how environmental factors, such as trace-nutrient limitation, influence this role is lacking. Here, we examine biofilm development by Pseudomonas putida in media either deficient or sufficient in Fe during growth on biotite, an Fe rich mineral, or on glass. We hypothesized that the bacteria would respond to Fe deficiency by enhancing biotite dissolution and by the formation of binding sites to inhibit Fe leaching from the system. Glass coupons acted as a no-Fe control to investigate whether biofilm response depended on the presence of Fe in the supporting solid. Biofilms grown on biotite, as compared to glass, had significantly greater biofilm biomass, specific numbers of viable cells (SNVC), and biofilm cation concentrations of K, Mg, and Fe, and these differences were greater when Fe was deficient in the medium. Scanning electron microscopy (SEM) confirmed that biofilm growth altered the biotite surface, smoothing the rough, jagged edges of channels scratched by hand on the biotite, and dissolving away small, easy-to access particles scattered across the planar surface. High-resolution magic angle spinning proton nuclear magnetic resonance (HRMAS 1 H NMR) spectroscopy showed that, in the Fe-deficient medium, the relative amount of polysaccharide nearly doubled relative to that in biofilms grown in the medium amended with Fe. The results imply that the bacteria responded to the Fe deficiency by obtaining Fe from biotite and used the biofilm matrix to enhance weathering and as a sink for released cation nutrients. These results demonstrate one mechanism by which biofilms may help soil microbes overcome nutrient deficiencies in oligotrophic systems. PMID- 27384344 TI - Acute kidney injury: from clinical to molecular diagnosis. AB - The RIFLE classification was introduced in 2004 to describe the presence of acute kidney injury (AKI) and to define its clinical stage, based upon the serum creatinine level and urine output. The same criteria, although slightly modified, are used in the other scoring systems AKIN and KDIGO. Mortality and morbidity remain high in AKI, suggesting that current diagnostic methods are suboptimal, poorly accurate, and often timely inadequate in detecting the presence of early kidney injury. Conversely, a growing body of evidence indicates that new AKI biomarkers can be used to both rule out AKI and to assess high-risk conditions or the presence of subclinical forms. Neutrophil gelatinase-associated lipocalin or cell cycle arrest biomarkers seem to be sensitive and specific enough to be used in conjunction with existing markers of AKI for better classifying renal injury as well as dysfunction. Improvements in diagnosis, risk identification, stratification, prognosis, and therapeutic monitoring may improve prevention and protection from organ damage and help to identify patients at risk, allowing individualized therapy. In this view, we may say that AKI diagnosis has finally moved from clinical to molecular level with potential benefits for the patients because similar progress has been shown in other disciplines. PMID- 27384345 TI - Small cell lung cancer: Time to revisit DNA-damaging chemotherapy. AB - Rational use of DNA-damaging chemotherapy, with new combinations to heighten DNA replication stress, could improve outcomes in small cell lung cancer. PMID- 27384346 TI - Radiocarbon dating reveals minimal collagen turnover in both healthy and osteoarthritic human cartilage. AB - The poor regenerative capacity of articular cartilage presents a major clinical challenge and may relate to a limited turnover of the cartilage collagen matrix. However, the collagen turnover rate during life is not clear, and it is debated whether osteoarthritis (OA) can influence it. Using the carbon-14 ((14)C) bomb pulse method, life-long replacement rates of collagen were measured in tibial plateau cartilage from 23 persons born between 1935 and1997 (15 and 8 persons with OA and healthy cartilage, respectively). The (14)C levels observed in cartilage collagen showed that, virtually, no replacement of the collagen matrix happened after skeletal maturity and that neither OA nor tissue damage, per se, influenced collagen turnover. Regional differences in (14)C content across the joint surface showed that cartilage collagen located centrally on the joint surface is formed several years earlier than collagen located peripherally. The collagen matrix of human articular cartilage is an essentially permanent structure that has no significant turnover in adults, even with the occurrence of disease. PMID- 27384347 TI - Robust classification of bacterial and viral infections via integrated host gene expression diagnostics. AB - Improved diagnostics for acute infections could decrease morbidity and mortality by increasing early antibiotics for patients with bacterial infections and reducing unnecessary antibiotics for patients without bacterial infections. Several groups have used gene expression microarrays to build classifiers for acute infections, but these have been hampered by the size of the gene sets, use of overfit models, or lack of independent validation. We used multicohort analysis to derive a set of seven genes for robust discrimination of bacterial and viral infections, which we then validated in 30 independent cohorts. We next used our previously published 11-gene Sepsis MetaScore together with the new bacterial/viral classifier to build an integrated antibiotics decision model. In a pooled analysis of 1057 samples from 20 cohorts (excluding infants), the integrated antibiotics decision model had a sensitivity and specificity for bacterial infections of 94.0 and 59.8%, respectively (negative likelihood ratio, 0.10). Prospective clinical validation will be needed before these findings are implemented for patient care. PMID- 27384349 TI - Systemic sclerosis: rehabilitation as a tool to cope with disability. AB - In patients with systemic sclerosis (SSc), local disability of the hands and face, due to the involvement of skin, subcutaneous tissues and musculoskeletal system, is scarcely improved by pharmacological therapy, but may be treated efficaciously with rehabilitation, which can prevent and reduce local disability, thus ameliorating global disability and impaired Quality of Life, related to changes in the hands and face. In SSc, in order to be efficacious, rehabilitation should: 1. include and use both local treatments of hands and face and global rehabilitation techniques; 2. be different according to the different SSc phases and subsets; 3. include different techniques to tailor treatment to the personal needs and abilities of the patients. PMID- 27384350 TI - Inhibition of 2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) Formation by Alkoxy Radical Scavenging of Flavonoids and Their Quantitative Structure Activity Relationship in a Model System. AB - The inhibitory effect of 10 flavonoids on the formation of 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine (PhIP) in a creatinine-phenylalanine model system was investigated through electronic spin resonance and a quantitative structure activity relationship. Alkoxy radicals were observed during the heating process, providing evidence for a radical pathway in the formation of PhIP. The alkoxy radical scavenging capability of the flavonoids was proportional to their inhibition of PhIP formation (IC50 ). We deduced that flavonoid inhibition of PhIP generation occurs via scavenging of alkoxy radicals during the heating process. Multiple linear regression and partial least squares models were used to elucidate the relationship between PhIP inhibition activity and structure characteristics of the flavonoids. The lipo-hydro partition coefficient and molecular fractional polar surface area of the flavonoids were found to be predictive of the inhibition effect. PMID- 27384348 TI - Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. AB - Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify patients at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively parallel sequencing-based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected postoperatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of 164 patients with negative ctDNA [hazard ratio (HR), 18; 95% confidence interval (CI), 7.9 to 40; P < 0.001]. In patients treated with chemotherapy, the presence of ctDNA after completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8 to 68; P = 0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence. PMID- 27384351 TI - Sweat patterns differ between tilt-induced reflex syncope and tilt-induced anxiety among youth. AB - PURPOSE: Profound sweating can occur with reflex-syncope and with emotional distress, but little is known about the similarities and differences between these sweat responses when they occur during orthostatic challenge. We sought to characterize and compare the sweat patterns related to tilt-induced syncope, presyncope, anxiety, and normal tilt testing. METHODS: In a prospective observational study, quantitative sweat rate was measured from the abdomen, forearm, ankle, and thigh during head-upright tilt. Sweat characteristics were compared across tilt diagnoses of syncope, presyncope, anxiety, and normal testing. When anxiety and syncope/presyncope occurred during the same study (separated by >=6 min), both were diagnosed. RESULTS: Our cohort comprised150 patients (15.1 +/- 2.3 years; 82.9 % female) with 156 diagnoses: 76 with reflex syncope, 31 with presyncope, 23 with anxiety, and 26 with normal results. All syncope/presyncope patients and 20 (87 %) of the anxiety patients had corresponding sweat responses. Minimal or negligible sweating occurred among patients with normal tests. Neither basal sweat (19.4 +/- 4.7 versus 18.3 +/- 3.7 versus 18.5 +/- 3.7 nL/min/cm(2)) nor peak sweat (171 +/- 47.4 versus 149.4 +/- 64.4 versus 154.4 +/- 59.2 nL/min/cm(2)) differed between patients with syncope, presyncope, or anxiety, p = .32 and p = .12, respectively. However, the qualitative sweat patterns related to syncope/presyncope (diffuse, smoothly contoured, symmetrical, single peaks) differed considerably from the sweat patterns related to anxiety (heterogeneous, asymmetrical, roughly contoured single-peak, multi-peak, or progressive sweat changes). CONCLUSIONS: The sweat patterns related to syncope/presyncope are distinguishable from the sweat patterns related to anxiety. Recognition of the different sweat patterns can inform how signs and symptoms are interpreted during clinical orthostatic challenge. PMID- 27384352 TI - Childhood pneumonia - the Drakenstein Child Health Study. AB - Advances in immunisation, improvements in socioeconomic status and effective HIV prevention and treatment strategies have reduced the population burden of childhood pneumonia and severe disease. However, pneumonia remains the major single cause of death in children outside the neonatal period, causing approximately 1 million deaths annually, or 15% of an estimated 6.3 million deaths in children aged under 5 years. This burden is disproportionately high in low- and middle-income countries and in Africa, where almost 50% of deaths in children aged under 5 years occur, despite African children comprising only 25% of live births globally. Pneumonia incidence and severity are highest in the first year of life, especially in the first 6 months. PMID- 27384353 TI - Overview of the 2016 South African Health Review. AB - The Global Report on Urban Health: Equitable, Healthier Cities for Sustainable Development, issued in March 2016 by the World Health Organization and the United Nations Human Settlements Programme (UN-Habitat), emphasises the need for enhanced governance and leadership to achieve universal health coverage and the Sustainable Development Goals. Noting that a healthy population forms the foundation for 'sustainable economic growth, social stability, and full realisation of human potential', the report presents 'practical, proven solutions for working across sectors to tackle these ... health challenges', and includes examples of such successes in South Africa. PMID- 27384354 TI - The impact of HIV infection on the presentation of lung cancer in South Africa. AB - BACKGROUND: Despite the very high background prevalence of HIV and smoking related diseases in sub-Saharan Africa, very little is known about the presentation of lung cancer in HIV-infected individuals. METHODS: We prospectively compared HIV-positive (n=44) and HIV-negative lung cancer patients (n=425) with regard to demographics, cell type, performance status and umour node metastasis staging at initial presentation. RESULTS: HIV-positive patients were found to be younger than HIV-negative (mean 54.1 (standard deviation (SD) 8.4) years v. 60.5 (10) years, p<0.01), more likely to have squamous cell carcinoma (43.2% v. 30.1%, p=0.07) and significantly more likely to have a poor Eastern Cooperative Oncology Group (ECOG) performance status of >=3 (47.7% v. 29.4%, p=0.02). In the case of non-small cell-lung cancer, they were also significantly less likely to have early stage lung cancer (0% v. 10.3%, p=0.02) compared with HIV-negative patients. CONCLUSIONS: HIV-positive lung cancer patients were younger, significantly more likely to have a poor performance status at presentation and significantly less likely to have early stage lung cancer when compared with HIV-negative patients. PMID- 27384355 TI - Review of the 2015 Guidelines for Maternity Care with relevance to congenital disorders. AB - The 4th edition of the Guidelines for Maternal Care in South Africa published by the National Department of Health in 2015 was evaluated with relevance to the care and prevention of congenital disorders (CDs). Disparate terminology is used for CDs throughout the guidelines, and overall less detail is included on CDs compared with the previous edition. This demonstrates a lack of awareness around the growing health need and contribution of CDs to the disease burden in South Africa (SA). Referrals to medical genetic services in the guidelines for mothers of advanced maternal age and other high-risk categories do not take into account the insufficient capacity available for screening and diagnosis of CDs. This highlights the lack of consultation with the medical genetics sector during the development of the guidelines. To respond to the Sustainable Development Goals by 2030, CDs must be integrated comprehensively at all levels of healthcare in SA. PMID- 27384356 TI - Ending preventable child deaths in South Africa: What role can ward-based outreach teams play? AB - South Africa (SA) has emerged from the Millennium Development Goal era with a mixture of success and failure. The successful national scale-up of prevention of mother-to-child transmission of HIV services with increasingly efficacious antiretroviral regimens has reduced the mother-to-child transmission rate dramatically; however, over the same period there appears to have been no progress in coverage of high-impact interventions for pneumonia and diarrhoea, which are now leading causes of under-5 mortality. SA embarked on a strategy to re-engineer the primary healthcare system in 2011, which included the creation of ward-based outreach teams consisting of community health workers (CHWs). In this article we argue that the proposed ratio of CHWs to population is too low for public health impact and that the role and scope of CHWs should be extended beyond giving of health information to include assessment and treatment of childhood illnesses (particularly diarrhoea and suspected pneumonia). Evidence and experience amply demonstrate that CHWs in sufficient density can have a rapid and positive impact on neonatal and young child mortality, especially when they are allowed to treat common acute conditions. SA's mediocre performance in child survival could be dramatically improved if there were more CHWs who were allowed to do more. PMID- 27384357 TI - The Expanded Programme on Immunisation in South Africa: A story yet to be told. AB - During the past two decades, immunisation has saved millions of lives and prevented countless illnesses and disabilities in South Africa(SA). However, vaccine-preventable diseases are still a threat. A vaccine-preventable disease that might lead to a 1- or 2-week illness in anadult, could prove deadly for infants, children or elderly people. Vaccination protects oneself and one's family. For example, adults are themost common source of pertussis (whooping cough) infection in infants, which can be deadly for the latter. This article demonstrates thecommitment of the SA government to immunisation, highlights key milestones of the Expanded Programme on Immunisation (EPI) anddispels the myth that the EPI in SA is in shambles. PMID- 27384358 TI - Social justice and research using human biological material: A response to Mahomed, Nothling-Slabbert and Pepper. AB - Social justice in the context of research using human biological material is an important contemporary legal-ethical issue. A question at the heart of this issue is the following: Is it fair to expect a research participant (a person who participates in such research by, among others, making available biological material from his or her body) to participate on an altruistic basis, while the researchers and the investors in the research can gain commercially from the research? In a recent article, Mahomed, Nothling-Slabbert and Pepper proposed that research participants should be entitled to share in the profits emanating from such research via a proposed new statutory right to the intellectual property emanating from such research. In order to stimulate debate on this important issue of social justice, this article responds to the position of Mahomed et al. by focusing on two main points: Firstly, I contend that Mahomed et al. fail to make a convincing argument in favour of shifting away from altruism; secondly, I caution against framing the debate in terms of the binary poles of altruism v. profitsharing, and suggest that should healthcare public policy ever move away from altruism, various non-monetary forms of benefit-sharing by research participants should be considered. PMID- 27384359 TI - Public health officials and MECs should be held liable for harm caused to patients through incompetence, indifference, maladministration or negligence regarding the availability of hospital equipment. AB - There have been several reports of state hospitals not having functional equipment such as radiological equipment. Where these are due to incompetence, Indifference, maladministration or negligence by the public officials concerned, they may be held personally liable for the resulting harm to patients. However, the courts have often observed that where the State has been sued vicariously for the wrongs of public officials, it has not obtained reimbursement from the offending official. It has therefore been suggested that irresponsible public servants should be sued in their personal capacity (in addition to the State), to prevent taxpayers always having to pay for their misdeeds. If an individual public official cannot afford to pay all the damages awarded, the injured party can recover the balance from the State by citing it as a vicarious joint wrongdoer. PMID- 27384360 TI - Legal access to surrogate motherhood in illness that does not cause infertility. AB - The threshold requirement for surrogate motherhood entails that a commissioning parent or parents must be permanently unable to give birth to a child. The question of whether a commissioning mother who suffers from a permanent illness that does not cause infertility as such, but that renders pregnancy a significant health risk to such mother and/or to her prospective child in utero, has arisen in practice. In this article, I propose that the inability to give birth to a child as per the threshold requirement should not be interpreted narrowly as referring only to a commissioning parent's inherent inability to give birth to a child, but should rather be interpreted broadly as referring only to a commissioning parent's effective inability to give birth to a child - allowing consideration of the medical sequelae of pregnancy for the commissioning mother and her prospective child. I argue that such a broad interpretation of the threshold requirement is compatible with legislative intent and case law, and is demanded by our country's constitutional commitment to human rights. PMID- 27384361 TI - Resolution of a periodontoid rheumatoid pannus mass in an elderly patient treated with a rigid cervical collar: A case report and literature review. AB - In patients with C2 rheumatoid pannus with spinal cord compression the treatment of choice is extensive surgery either through a transoral resection of the dens axis or a dorsal stabilisation, or both. We present a case of an 11-mm rheumatoid pannus with significant compression of the spinal cord, which failed surgical treatment with respect to dorsal stabilisation. Therefore, rigid cervical collar for 8 weeks followed by soft collar for another 4 weeks was chosen as a treatment option. During the follow-up period of 1 year, the pannus reduced significantly and the spinal cord decompressed. In cases where surgery is not an option or is technically very demanding, the alternative of cervical collar immobilisation is a satisfying option. PMID- 27384362 TI - A case of refractory thrombotic thrombocytopenic purpura treated with plasmapheresis and rituximab. AB - Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disorder with no prevalence or incidence studies in sub-Saharan Africa. Acquired TTP has several causes, all of which lead to decreased activity of von Willebrand factor cleaving protease (ADAMTS13) due to autoantibodies that are directed towards ADAMTS13. We report a case of a 46-year-old man who presented with most of the classic clinical manifestations of TTP. PMID- 27384363 TI - Schwannoma extending from the umbilical region to the mid-thigh, compressing the major vessels of the right leg: A case report and review of the literature. AB - Schwannomas are benign, usually encapsulated, nerve sheath tumours derived from Schwann cells. They commonly arise from the cranial nerves as acoustic schwannomas and are extremely rare in the pelvis and retroperitoneal area (<0.5% of reported cases) unless they are combined with Von Recklinghausen disease (type 1 neurofibromatosis). We report the case of a 23-year-old woman with a mass extending from the umbilical region in the abdomen to the upper two-thirds of the thigh. As this tumour is so rare, and in order to ensure optimal treatment and survival for our patient, a computed tomography-guided biopsy was performed before en bloc tumour excision. Because of the possibility of malignancy, complete excision of the mass was performed, with pelvic blunt dissection. Histological examination showed a benign neoplasm, originating from the cells of peripheral nerve sheaths; the diagnosis was a schwannoma. Abdominal schwannomas are rare neoplasms that can be misdiagnosed. Laparoscopy is a safe and efficient option for approaching benign pelvic tumours and may offer the advantage of better visualisation of structures owing to the magnification in laparoscopic view, especially in narrow anatomical spaces. However, in our case laparoscopy was not considered owing to the size and anatomical location of the tumour. PMID- 27384364 TI - Analysis of 5 years of morbidity and mortality conferences in a metropolitan South African trauma service. AB - BACKGROUND: Since 2008 the Pietermaritzburg Metropolitan Trauma Service (PMTS) has run a structured, self-reporting, metropolitan morbidity and mortality conference (MMC). In 2012 a hybrid electronic medical registry (HEMR) was introduced to capture routine data and to generate reports on morbidity and mortality. This paper reviews our experience in setting up a metropolitan MMC and compares the quality of the reported morbidity data from the pre- and post-HEMR era. METHODS: We compared data from the MMC before and after the introduction of the HEMR to audit the impact of these meetings on the reporting and analysis of surgical morbidity and mortality in our service. RESULTS: During the 4-year period from 2008 to 2011, a total of 208 MMCs were held. A total of 10 682 patients were admitted by the PMTS during that period, of whom 87% were males, and the mean age was 26 years. Penetrating trauma accounted for 40.9% (4 344/10 628) of the total workload. A total of 432 (4.1%) morbidities were identified. Of these, 36.6% (158) were related to human error, 32% (138/432) were related to surgical pathologies and the remaining 31.9% (136/432) were related to systemic diseases. There was an exponential increase in the reporting of morbidity each year. The total in-hospital mortality was 3% (358/10 682). Following the introduction of the HEMR, from 2012 to 2014, 6 217 patients were admitted. A total of 1 314 (21.1%) adverse events and 315 (5.1%) deaths were recorded by the HEMR. The adverse events were divided into 875 'pathology-related' morbidities and 439 'error-related' morbidities. CONCLUSIONS: The development of the MMC led to increased reporting of morbidity and mortality. The introduction of the HEMR resulted in a dramatic improvement in the capturing of morbidity and mortality data, suggesting that a paper-based self-reporting system tends to underestimate morbidity. Over one-third of all morbidities were related to human error. Common morbidities have been identified. PMID- 27384365 TI - [Not Available]. AB - BACKGROUND: Despite ranking third as a cause of hospital-acquired acute kidney injury (AKI), iatrogenic contrast-induced nephropathy (CIN) impacts significantly on morbidity and mortality and is associated with high hospital costs. In sub Saharan Africa, the rates and risk factors for CIN and patient outcomes remain unexplored. METHODS: We conducted a prospective observational study at the Charlotte Maxeke Johannesburg Academic Hospital, South Africa, from 1 July 2014 to 30 July 2015. Hospitalised patients undergoing computed tomography scan contrast media administration and angiography were consecutively recruited to the study and followed up for development of AKI. CIN was defined as an increase in serum creatinine >25% or an absolute increase of >44 MUmol/L from baseline at 48 72 hours post exposure to contrast media. Outcome variables were the occurrence of CIN, length of hospitalisation and in-hospital mortality. RESULTS: We recruited 371 hospitalised patients with a mean (standard deviation) age of 49.3 (15.9). The rates of CIN, assessed using an absolute or relative increase in serum creatinine from baseline, were 4.6% and 16.4%, respectively. Anaemia was an independent predictor for the development of CIN (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.01 - 2.87; p=0.04). The median serum albumin was 34 g/L (interquartile range (IQR) 29 - 39.5) and 38 g/L (IQR 31 - 42) in the CIN and control groups, respectively (p=0.01), and showed a significant trend for CIN development (RR 1.68, 95% CI 0.96 - 2.92; p=0.06). Mortality was significantly increased in the CIN group (22.4% v. 6.8%; p<0.001), and CIN together with anaemia increased mortality twofold (RR 2.39, 95% CI 1.20 - 4.75; p=0.01) and threefold (RR 3.32, 95% CI 1.48 - 7.43; p=0.003), respectively. CONCLUSIONS: CIN has a relatively high incidence in sub-Saharan Africa and predicts poorer clinical outcomes. The presence of CIN and anaemia positively predicted mortality. Caution should be exercised in patients with hypoalbuminaemia and anaemia undergoing contrast media administration. PMID- 27384366 TI - Glomerular disease and acute kidney injury in Sudan: Demographics, histological diagnosis and outcome. AB - BACKGROUND: Acute kidney injury (AKI) is a relatively common clinical condition, associated with high rates of mortality. Although there is extensive literature on the nature and consequence of AKI in the developed world, much less is known in the developing world and more specifically in sub-Saharan Africa (SSA). OBJECTIVES: To describe the demographics, histological diagnosis and clinical course of patients presenting with AKI to a single centre in Sudan. METHODS: Retrospective data were collected on 100 consecutive patients with AKI and an active urinary sediment, who underwent diagnostic native percutaneous renal biopsy. RESULTS: The mean (standard deviation) age of those biopsied was 33.6 (14.1) years of age, with a preponderance (58%) of females. The most common clinical indications for biopsy were AKI associated with haematuria and proteinuria (72%), AKI and proteinuria (22.5%) or AKI and haematuria (5%). The frequencies of the most common primary glomerulonephritides (GN) were focal segmental GN (15%) and mesangiocapillary GN (8%). Lupus nephritis was the most frequent secondary GN associated with AKI (31%) and the most common overall histological diagnosis. Peak creatinine, but not oliguria, at presentation predicted likelihood of remaining dialysis-dependent. Age at presentation but not baseline renal function by estimated glomerular filtration rate (eGFR), was associated with the likelihood of having residual chronic kidney disease following an episode of AKI. CONCLUSIONS: The data suggested differences in the pattern of intrinsic renal/glomerular disease leading to AKI to those published and mainly derived from the developed world and patients in SSA. PMID- 27384367 TI - Major decline in malaria morbidity and mortality in the Union of Comoros between 2010 and 2014: The effect of a combination of prevention and control measures. AB - BACKGROUND: Malaria remains a public health challenge in sub-Saharan Africa. In response to this, many countries are working towards achieving the World Health Assembly and Roll Back Malaria Partnership target of a 75% decline in malaria incidence. OBJECTIVE: To assess trends in malaria morbidity and mortality in the three islands of the Comoros Archipelago from 2010 to 2014. METHODS: This was a retrospective study in which all confirmed malaria cases and deaths recorded between 2010 and 2014 were accessed from the national malaria control database. Trends and comparisons in malaria incidence and case fatality rates for all age groups, including under-5 children and pregnant women, were analysed using Microsoft Excel and SPSS version 16. RESULTS: A substantial decline in malaria incidence was observed for each island between 2010 and 2014; from 75.98 cases per 1 000 population in 2010 to 0.14 in 2014 in Moheli, 60.60 to 0.02 in Anjouan and 235.36 to 5.47 in Grand Comoro. Additionally, a general reduction in malaria case fatalities was observed. In Moheli, there were no case fatalities between 2010 and 2014, while there was a decline in the case fatality rate in Anjouan (from 1.20 fatalities per 1 000 cases to 0) and Grand Comoros (0.51 to 0). There were also significant differences (p<0.05) in malaria incidence and case fatalities between the three islands. A similar trend was observed for pregnant women and under-5 children. CONCLUSIONS: Our study indicates a significant decline in malaria morbidity and mortality in the islands of Moheli, Anjouan and Grand Comoro from 2010 to 2014. This considerable reduction is attributed to a combination of malaria prevention and control interventions implemented during the study period. PMID- 27384368 TI - Measles outbreak reveals measles susceptibility among adults in Namibia, 2009 - 2011. AB - BACKGROUND: The World Health Organization, African Region, set the goal of achieving measles elimination by 2020. Namibia was one of seven African countries to implement an accelerated measles control strategy beginning in 1996. Following implementation of this strategy, measles incidence decreased; however, between 2009 and 2011 a major outbreak occurred in Namibia. METHODS: Measles vaccination coverage data were analysed and a descriptive epidemiological analysis of the measles outbreak was conducted using measles case-based surveillance and laboratory data. RESULTS: During 1989 - 2008, MCV1 (the first routine dose of measles vaccine) coverage increased from 56% to 73% and five supplementary immunisation activities were implemented. During the outbreak (August 2009 - February 2011), 4 605 suspected measles cases were reported; of these, 3 256 were confirmed by laboratory testing or epidemiological linkage. Opuwo, a largely rural district in north-western Namibia with nomadic populations, had the highest confirmed measles incidence (16 427 cases per million). Infants aged <=11 months had the highest cumulative age-specific incidence (9 252 cases per million) and comprised 22% of all confirmed cases; however, cases occurred across a wide age range, including adults aged >=30 years. Among confirmed cases, 85% were unvaccinated or had unknown vaccination history. The predominantly detected measles virus genotype was B3, circulating in concurrent outbreaks in southern Africa, and B2, previously detected in Angola. CONCLUSION: A large-scale measles outbreak with sustained transmission over 18 months occurred in Namibia, probably caused by importation. The wide age distribution of cases indicated measles susceptible individuals accumulated over several decades prior to the start of the outbreak. PMID- 27384369 TI - How long are elderly patients followed up with mammography after the diagnosis of breast cancer? A single-centre experience in a developing country. AB - BACKGROUND: The effect of breast cancer on elderly South African (SA) patients is not well characterised. The lack of data with regard to disease burden, post treatment surveillance and breast cancer relapse poses a challenge to providing optimum follow-up care to this group of patients. OBJECTIVES: To assess the effect of breast cancer and adherence to post-treatment surveillance programmes among the local elderly population attending the breast oncology clinics at Addington and Inkosi Albert Luthuli Central hospitals in Durban, KwaZulu-Natal, SA. METHODS: A retrospective review was undertaken of all patients aged >=65 years diagnosed with breast cancer during 2007. Hospital records were reviewed for a period of 5 years to ascertain the stage of the disease, treatment received, adherence to post-treatment surveillance mammograms, incidence of new mammographic findings and recurrence, site of recurrence, mode of detection of recurrence, disease-free survival, and overall survival rates at 5 years. RESULTS: In our study, the incidence of breast cancer in the elderly population was 26.7%. A significant percentage of patients (56.3%) were diagnosed at an advanced stage of disease. Of the 46.9% who had received surveillance mammography, only 6.3% received their post-treatment surveillance mammograms on time, in accordance with international recommendations. New mammographic findings were detected in 26.7% of patients during the 5-year follow-up. During the follow up period, 15.6% of the total number of study patients presented with disease recurrence. Eighty percent of cases of recurrence were detected clinically. The overall survival at 5 years was 65.6%. CONCLUSION: Our study highlights the significant number of elderly patients with advanced disease at diagnosis, poor compliance with internationally recommended annual post-treatment surveillance mammograms, and the relatively low overall 5-year survival rate compared with that of international studies. PMID- 27384370 TI - High prevalence of primary dyslipidaemia in black South African patients at a tertiary hospital in northern Gauteng, South Africa. AB - BACKGROUND: The prevalence of cardiovascular disease is projected to be 38.7% for the USA in 2020, including coronary heart disease at 8.6% and stroke at 3.6%. In South Africa (SA), premature deaths due to heart and blood vessel diseases in people of working age (35 - 64 years) have been predicted to increase by 41% between 2007 and 2030, with enormous negative economic impact. Atherosclerosis underlies much of the pathogenesis, which involves risk factors including dyslipidaemia. Secondary dyslipidaemia associated with diabetes mellitus, hypothyroidism, chronic renal disease, cholestasis, nephrotic syndrome, alcohol excess, drugs such as thiazide diuretics and antiretroviral agents may respond to treatment of underlying causes, but residual dyslipidaemia may in such cases be due to primary disorders of metabolism. Primary dyslipidaemias are uncommon and to a large extent underdiagnosed, especially in the black population of SA, reflecting a lack of clinical and laboratory awareness or expertise. Specific diagnoses enable effective intervention in the patients as well as the families. OBJECTIVE: To assess the burden and prevalence of dyslipidaemia in the SA black population at Dr George Mukhari Hospital in the north region of Gauteng. METHOD: A retrospective data analysis of 12-month lipid profiles comprising triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol and directly measured low-density lipoprotein (LDL) cholesterol (LDLC). RESULTS: There were 24 656 requests for 6 348 patients. The lipid cut-off levels were somewhat arbitrary but were based on the commonly used decision-making levels in the treatment guidelines. Severe hypercholesterolaemia (>7 mmol/L) was seen in 299 (4.7%) patients and extreme hypercholesterolaemia (>12 mmol/L) was seen in 30 (0.5%) patients. LDLC (>5 mmol/L) occurred in 80 (1.3%) patients and >10 mmol/L in 19 (0.3%) patients. A predominant triglyceride problem was seen in 578 (9.1%) patients with TG (>2 mmol/L) and TC (<5 mmol/L), whereas moderate hypertriglyceridaemia (>5 mmol/L) was present in 113 (1.8%) patients, and more severe hypertriglyceridaemia (>10 mmol/L) in 10 (0.2%). TC (>5 mmol/L) with LDL (>3 mmol/L) but TG in the normal range was seen in 369 (5.8%) patients, indicating a cholesterol-predominant problem. In contrast, LDLC (>3 mmol/L) and TG (>1.7 mmol/L) was seen in 249 (3.87%) representing mixed hyperlipidaemia. Paediatric patients with severe dyslipidaemia mostly suffered from nephrotic syndrome. CONCLUSION: A significant burden and a high prevalence of dyslipidaemias were present in adults in whom a monogenic disorder should be considered. The extent and severity of dyslipidaemia justify a special clinic and laboratory to ensure accurate diagnosis with effective intervention for patients and their families. PMID- 27384371 TI - Academic staff recruitment and retention challenges at the University of Botswana medical school. AB - BACKGROUND: Sub-Saharan Africa has a greater share of the global burden of disease, poverty, and inadequate human resources for health compared with other regions of the world. Botswana, as other regional countries, is failing to successfully recruit and retain academics at its medical school. OBJECTIVES: To document the medical school's staff recruitment and retention trends and challenges, and to propose possible solutions. METHODS: This was a descriptive research study involving review and analysis of the University of Botswana medical school's staff number targets, actual numbers on post, and other relevant publicly available university documents. The numbers and country of origin of staff recruited from 2008 to 2013 were recorded. Net staff gain or loss per year was then calculated. Student numbers were analysed and related to staff availability. As there was a multilevel change in university management in 2011, the periods and events before and after April 2011 were analysed. Publicly available University of Botswana documents about the university's organisational structure, policies, and processes were reviewed. RESULTS: Over a 5-year period, the school recruited 74 academics worldwide; 30 of them left the school. Retention was a greater challenge than recruitment. The school had difficulty recruiting locals and senior academics, regardless of specialty. It appears that staff loss occurred regardless of country of origin. CONCLUSION: The authors suggest that multilevel change in management was one of the most likely contributors to the school's recruitment and retention challenges. The University of Botswana must comprehensively address these. PMID- 27384372 TI - Burkitt's lymphoma patients in Northwest Cameroon have a lower incidence of sickle cell trait (Hb AS) than healthy controls. AB - Contradictory findings have been reported from Africa with regard to the risk of developing Burkitt's lymphoma (BL) in sickle cell trait (AS)carriers. Haemoglobin electrophoresis was performed in 78 BL patients in the Northwest region of Cameroon, and in 78 nearest-neighbourcontrols of the same age, sex and tribe from the same village. AS was confirmed in 4 of 78 (5.13%) BL patients and in 11 of 78 (14.10%)controls (chi2, p=0.052; Fisher's exact, one-tailed, p=0.050). Sickle cell trait carriers had a marginal statistically reduced risk of developing BL. PMID- 27384376 TI - Ibuprofen versus acetaminophen as a post-partum analgesic for women with severe pre-eclampsia: randomized clinical study. AB - OBJECTIVE: To compare differences in blood pressure levels between patients with severe post-partum pre-eclampsia using ibuprofen or acetaminophen. METHODS: A randomized controlled trial was made in women with severe pre-eclampsia or superimposed pre-eclampsia after vaginal birth. The patient was randomly selected to receive either 400 mg of ibuprofen every 8 h or 1 g of acetaminophen every 6 h during the post-partum. The primary variable was systolic hypertension >=150 mmHg and/or diastolic hypertension >=100 mmHg after the first 24 h post-partum. Secondary variables were the arterial blood pressure readings at 24, 48, 72, and 96 h post-partum and maternal complications. RESULTS: A total of 113 patients were studied: 56 in the acetaminophen group and 57 in the ibuprofen group. With regard to the primary outcome, more cases were significantly hypertensive in the ibuprofen group (36/57; 63.1%) than in the acetaminophen group (16/56; 28.6%). Severe hypertension (>=160/110 mmHg) was not significantly different between the groups, 14.5% (acetaminophen) and 24.5% (ibuprofen). The levels of arterial blood pressure show a hammock-shaped curve independent of the drug used, however, is more noticeable with ibuprofen. CONCLUSIONS: This study shows that ibuprofen significantly elevates blood pressure in women with severe pre-eclampsia during the post-partum period. PMID- 27384377 TI - Regulation of transcription factors via natural decoys in genomic DNA. AB - Eukaryotic genomic DNA contains numerous high-affinity sites for transcription factors. Only a small fraction of these sites directly regulates target genes. Other high-affinity sites can serve as naturally present decoys that sequester transcription factors. Such natural decoys in genomic DNA may provide novel regulatory mechanisms for transcription factors. PMID- 27384379 TI - Leukocyte telomere length in relation to the risk of Barrett's esophagus and esophageal adenocarcinoma. AB - Chronic inflammation and oxidative damage caused by obesity, cigarette smoking, and chronic gastroesophageal reflux disease (GERD) are major risk factors associated with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). EAC has been increasing the past few decades, and early discovery and treatment are crucial for survival. Telomere shortening due to cell division and oxidative damage may reflect the impact of chronic inflammation and could possibly be used as predictor for disease development. We examined the prevalence of shorter leukocyte telomere length (LTL) among individuals with GERD, BE, or EAC using a pooled analysis of studies from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). Telomere length was measured in leukocyte DNA samples by Q PCR. Participants included 1173 patients (386 with GERD, 384 with EAC, 403 with BE) and 736 population-based controls. The association of LTL (in tertiles) along the continuum of disease progression from GERD to BE to EAC was calculated using study-specific odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models adjusted for potential confounders. Shorter LTL were less prevalent among GERD patients (OR 0.57; 95% CI: 0.35-0.93), compared to population-based controls. No statistically significant increased prevalence of short/long LTL among individuals with BE or EAC was observed. In contrast to some earlier reports, our findings add to the evidence that leukocyte telomere length is not a biomarker of risk related to the etiology of EAC. The findings do not suggest a relationship between LTL and BE or EAC. PMID- 27384380 TI - A novel role of Beclin-1, cytokinetic abscission. PMID- 27384382 TI - Monitoring trihalomethanes in chlorinated waters using a dispersive liquid-liquid microextraction method with a non-chlorinated organic solvent and gas chromatography-mass spectrometry. AB - The environmental monitoring of trihalomethanes (THMs) has been performed by setting up a dispersive liquid-liquid microextraction method in combination with gas chromatography (GC)-mass spectrometry (MS). The optimized method only requires ~26 uL of decanol as extractant solvent, dissolved in ~1 mL of acetone (dispersive solvent) for 5 mL of the environmental water containing THMs. The mixture is then subjected to vortex for 1 min and then centrifuged for 2 min at 3500 rpm. The microdroplet containing the extracted THMs is then sampled with a micro-syringe, and injected (1 uL) in the GC-MS. The method is characterized for being fast (3 min for the entire sample preparation step) and environmentally friendly (low amounts of solvents required, being all non-chlorinated), and also for getting average relative recoveries of 90.2-106% in tap waters; relative standard deviation values always lower than 11%; average enrichment factors of 48 49; and detection limits down to 0.7 ug.L-1. Several waters: tap waters, pool waters, and wastewaters were successfully analyzed with the method proposed. Furthermore, the method was used to monitor the formation of THMs in wastewaters when different chlorination parameters, namely temperature and pH, were varied. PMID- 27384381 TI - Low dose rate brachytherapy (LDR-BT) as monotherapy for early stage prostate cancer in Italy: practice and outcome analysis in a series of 2237 patients from 11 institutions. AB - OBJECTIVE: Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure. METHODS: Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 ((125)I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. (125)I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145 Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes. RESULTS: Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p < 0.0001) and V100 (p = 0.09) were correlated with BFFS, with V100 effect significantly different between patients at low risk and those at intermediate/high risk (p = 0.04). Short follow-up and lack of toxicity data represent the main limitations for a global evaluation of LDR-BT. CONCLUSION: This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer. ADVANCES IN KNOWLEDGE: Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome. PMID- 27384383 TI - Patient experience after lower extremity amputation for sarcoma in England: a national survey. AB - PURPOSE: After amputation, rehabilitation and limb fitting services are critically important to optimise outcomes. We investigated the reported patient experience and variation in limb fitting services after amputation for musculoskeletal tumours in England. METHODS: A postal survey instrument was developed following literature review, patient and clinician consultation and piloting. The survey was sent from each of the five bone tumour surgical centres in England. RESULTS: One hundred and five responses were received from 250 patients (42%). The number of limb fitting centres accessed by each surgical centre varied from 2 to 28. Many patients reported care falling short of national standards in areas including pre-amputation counselling, information provision, meeting someone with a similar amputation before surgery, psychological support and falls management. Patients were seen sooner where limb fitting services were on site. Many patients rely on being driven, ambulance and public transport to access services. CONCLUSION: This study demonstrates variation in the reported experience of limb fitting services by sarcoma patients. Areas for improvement include information provision, pre-amputation counselling, psychological support and falls management. Clinicians should be aware services are highly variable, and this may impact on outcomes. Patients treated in sarcoma centres with limb fitting services on site may experience better care. Implications for Rehabilitation Rehabilitation services should strive to meet agreed national standards consistently. Where preamputation counselling involving meeting someone with a similar amputation is not possible, good information including video could be helpful. Services should support rehabilitation in the form of early walking aids and efficient prosthetic repair and maintenance. Psychological support, occupational therapy and physiotherapy support must be provided in the acute and chronic phases, including access to long-term rehabilitation care. Rehabilitation programmes must include training to patients and families on reporting, prevention and management of falls. On site services may support better care. Mechanisms for delivering expert specialist care close to home are needed. PMID- 27384384 TI - Thermodynamics of quantum systems with multiple conserved quantities. AB - Recently, there has been much progress in understanding the thermodynamics of quantum systems, even for small individual systems. Most of this work has focused on the standard case where energy is the only conserved quantity. Here we consider a generalization of this work to deal with multiple conserved quantities. Each conserved quantity, which, importantly, need not commute with the rest, can be extracted and stored in its own battery. Unlike the standard case, in which the amount of extractable energy is constrained, here there is no limit on how much of any individual conserved quantity can be extracted. However, other conserved quantities must be supplied, and the second law constrains the combination of extractable quantities and the trade-offs between them. We present explicit protocols that allow us to perform arbitrarily good trade-offs and extract arbitrarily good combinations of conserved quantities from individual quantum systems. PMID- 27384385 TI - Stage-directed individualized therapy in esophageal cancer. AB - Esophageal cancer is the eighth most common cancer worldwide, and the incidence of esophageal carcinoma is rapidly increasing. With the advent of new staging and treatment techniques, esophageal cancer can now be managed through various strategies. A good understanding of the advances and limitations of new staging techniques and how these can guide in individualizing treatment is important to improve outcomes for esophageal cancer patients. This paper outlines the recent progress in staging and treatment of esophageal cancer, with particularly attention to endoscopic techniques for early-stage esophageal cancer, multimodality treatment for locally advanced esophageal cancer, assessment of response to neoadjuvant treatment, and the role of cervical lymph node dissection. Furthermore, advances in robot-assisted surgical techniques and postoperative recovery protocols that may further improve outcomes after esophagectomy are discussed. PMID- 27384386 TI - Functional regulatory roles of microRNAs in atherosclerosis. AB - MicroRNAs are a group of endogenously small non-coding RNA molecules that downregulate gene expression at the post-transcriptional level through binding to the 3'UTR of target mRNAs. Recent findings have revealed a key role for microRNAs in the pathophysiological processes of atherosclerosis. As a complex disease, atherosclerosis is influenced by a combination of multiple genes and environmental factors. Both of them play a role in atherogenesis by affecting different types of cells (such as endothelial cell, vascular smooth muscle cell and monocyte/macrophage) function. MicroRNAs control the senescence and dysfunction of endothelial cells, proliferation and migration of vascular smooth muscle cells, and macrophage-driven cytokine production and polarization. By these effects, microRNAs can influence the processes of atherosclerosis and may represent new molecular targets for therapy. PMID- 27384394 TI - Non-target impurity profiling of marketplace Cetirizine using high-resolution mass spectrometry and multivariate data analysis. AB - RATIONALE: As always, drug impurity is the first concern of medication safety. The quality of pre- and post-marketed drugs is estimated through systematic analysis of potential hazardous substances by impurity profiling. Impurity profile is the general name of all unwanted materials which may affect the purity of an active pharmaceutical ingredient (API). The safety of original drugs is guaranteed by an enormous amount of animal experiments and clinical research while the safety of generic drugs should also be ensured by comparative analysis for consistency evaluation. The significantly differential impurities between them should be focused on and the toxicity should be further estimated if necessary. Herein, we take a marketplace drug named Cetirizine as an example to investigate if there was a method which could effectively discover the potential markers among Cetirizine tablets with different brands and describe specific impurity profiling which makes the unknown brand of Cetirizine tablets predictable. METHODS: Liquid chromatography coupled with high-resolution mass spectrometry (LC/HRMS) was applied to capture the characteristic features of the impurity profile for three brands of marketplace Cetirizine tablets using full scan data-dependent MS/MS scan mode (FS-ddMS(2) ). RESULTS: Unsupervised learning: principal component analysis (PCA) and supervised learning: consensus orthogonal partial least squares discriminant analysis (OPLS-DA) were utilized to reveal the essential character of Cetirizine impurity profile; 16 differential impurities were finally found, their structures were speculated by HRMS(2) data. CONCLUSIONS: The cause of formation was further elucidated which gave a suggestion for production process optimization. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27384395 TI - The Psychopharmacology Algorithm Project at the Harvard South Shore Program: An Algorithm for Generalized Anxiety Disorder. AB - This revision of previous algorithms for the pharmacotherapy of generalized anxiety disorder was developed by the Psychopharmacology Algorithm Project at the Harvard South Shore Program. Algorithms from 1999 and 2010 and associated references were reevaluated. Newer studies and reviews published from 2008-14 were obtained from PubMed and analyzed with a focus on their potential to justify changes in the recommendations. Exceptions to the main algorithm for special patient populations, such as women of childbearing potential, pregnant women, the elderly, and those with common medical and psychiatric comorbidities, were considered. Selective serotonin reuptake inhibitors (SSRIs) are still the basic first-line medication. Early alternatives include duloxetine, buspirone, hydroxyzine, pregabalin, or bupropion, in that order. If response is inadequate, then the second recommendation is to try a different SSRI. Additional alternatives now include benzodiazepines, venlafaxine, kava, and agomelatine. If the response to the second SSRI is unsatisfactory, then the recommendation is to try a serotonin-norepinephrine reuptake inhibitor (SNRI). Other alternatives to SSRIs and SNRIs for treatment-resistant or treatment-intolerant patients include tricyclic antidepressants, second-generation antipsychotics, and valproate. This revision of the GAD algorithm responds to issues raised by new treatments under development (such as pregabalin) and organizes the evidence systematically for practical clinical application. PMID- 27384397 TI - Posttraumatic Stress Disorder, Overweight, and Obesity: A Systematic Review and Meta-analysis. AB - Previous reports have suggested a high prevalence of overweight and obesity among individuals with posttraumatic stress disorder (PTSD). Few studies, however, systematically analyze the relationship between PTSD and body mass index (BMI). We conducted a systematic review and meta-analysis aimed at estimating the association between PTSD and BMI. Fifty-four articles were reviewed, 30 of which (with 191,948 individuals with PTSD and 418,690 trauma-exposed individuals or healthy controls) were eligible for inclusion in the meta-analysis. The pooled standard mean difference, based on a random-effects model, was 0.41 (95% confidence interval, 0.28-0.54; z = 6.26; p < .001). Statistical heterogeneity between the included studies was high (p < .001; I = 99%). Despite limitations, the findings of this systematic review and meta-analysis suggest an association between PTSD and BMI. Furthermore, longitudinal studies tentatively indicate that PTSD may lead to an increase in BMI and, as such, to the development of overweight/obesity, particularly in women. Further prospective studies and research elaborating the nature and etiology of the association are required. PMID- 27384398 TI - Challenges in Managing Treatment-Refractory Obsessive-Compulsive Disorder and Tourette's Syndrome. PMID- 27384396 TI - Separating Fact from Fiction: An Empirical Examination of Six Myths About Dissociative Identity Disorder. AB - Dissociative identity disorder (DID) is a complex, posttraumatic, developmental disorder for which we now, after four decades of research, have an authoritative research base, but a number of misconceptualizations and myths about the disorder remain, compromising both patient care and research. This article examines the empirical literature pertaining to recurrently expressed beliefs regarding DID: (1) belief that DID is a fad, (2) belief that DID is primarily diagnosed in North America by DID experts who overdiagnose the disorder, (3) belief that DID is rare, (4) belief that DID is an iatrogenic, rather than trauma-based, disorder, (5) belief that DID is the same entity as borderline personality disorder, and (6) belief that DID treatment is harmful to patients. The absence of research to substantiate these beliefs, as well as the existence of a body of research that refutes them, confirms their mythical status. Clinicians who accept these myths as facts are unlikely to carefully assess for dissociation. Accurate diagnoses are critical for appropriate treatment planning. If DID is not targeted in treatment, it does not appear to resolve. The myths we have highlighted may also impede research about DID. The cost of ignorance about DID is high not only for individual patients but for the whole support system in which they reside. Empirically derived knowledge about DID has replaced outdated myths. Vigorous dissemination of the knowledge base about this complex disorder is warranted. PMID- 27384399 TI - Psychological Symptom Amplification: Are Psychological Symptoms Subject to "Somatization"-Like Processes? AB - Many patients demonstrate amplified somatic symptom experiences that are felt by providers to cause excessive distress and functional impairment, and that can be diagnostically misleading. Terms attached to these presentations include somatization, medically unexplained symptoms, and, most recently, somatic symptom disorder. The analogous amplification of psychological symptoms has not been considered. Accordingly, this column makes a case for discussion and investigation of psychological symptom amplification (PSA), a process made possible by the medical legitimization of certain types of human suffering. As various forms of psychological suffering gain greater medical legitimacy, PSA becomes increasingly relevant. Circumstantial evidence suggests that unrecognized PSA may distort research findings and clinical efficacy in psychiatry. The largely symptom-based nature of psychiatric diagnosis makes PSA a challenging, but necessary, object of further scientific and clinical scrutiny. PMID- 27384400 TI - Association between anti-apolipoprotein A-1 antibodies and cardiovascular disease in the general population. Results from the CoLaus study. AB - We aimed to determine the association between autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) and prevalent cardiovascular (CV) disease (CVD) as well as markers of CV risk in the general population. Cross-sectional data were obtained from 6649 subjects (age 52.6 +/- 10.7 years, 47.4 % male) of the population-based CoLaus study. CVD was defined as myocardial infarction, angina pectoris, percutaneous revascularisation or bypass grafting for ischaemic heart disease stroke or transient ischaemic attack, and was assessed according to standardised medical records. Anti-apoA-1 IgG and biological markers were measured by ELISA and conventional automated techniques, respectively. Prevalence of high anti-apoA-1 IgG levels in the general population was 19.9 %. Presence of anti-apoA-1 IgG was significantly associated with CVD [odds ratio 1.34, 95 % confidence interval (1.05-1.70), p=0.018], independently of established CV risk factors (CVRFs) including age, sex, hypertension, smoking, diabetes, low and high density lipoprotein cholesterol levels. The n=455 (6.8 %) study participants with a history of CVD (secondary prevention subgroup) presented higher median anti ApoA-1 IgG values compared with subjects without CVD (p=0.029). Among patients in the secondary prevention subgroup, those with positive anti-apoA-1 IgG levels had lower HDL (p=0.002) and magnesium (p=0.001) levels, but increased uric acid and high-sensitivity C-reactive protein levels (p=0.022, and p<0.001, respectively) compared to patients with negative anti-apoA-1 IgG levels. In conclusion, anti apoA-1 IgG levels are independently associated with CVD in the general population and also related to CV biomarkers in secondary prevention. These findings indicate that anti-apoA-1 IgG may represent a novel CVRF and need further study in prospective cohorts. PMID- 27384403 TI - Sudden unexplained early neonatal death or collapse: a national surveillance study. AB - BACKGROUND: The incidence of sudden unexpected early neonatal death (SUEND) or acute life-threatening events (ALTEs) is reported as 0.05/1,000 to 0.38/1,000 live births. There is currently no national system in Australia for reporting and investigating such cases. METHODS: A 3-y prospective, national surveillance study, run in collaboration with the Australian Pediatric Surveillance Unit (APSU). Data were provided by pediatricians reporting to APSU; and independently ascertained by the Coroner in two states (NSW and QLD) and the Newborn Early Transport Network in NSW. A detailed deidentified questionnaire was created. RESULTS: In NSW and QLD, the incidence was 0.1 and 0.08/1,000 live births, respectively. Forty-eight definitive cases were identified. Common causes included accidental asphyxia, cardiac disease, persistent pulmonary hypertension of the newborn, and sudden infant death syndrome. Twenty-six babies collapsed on day 1 and 19 were found on the carer's chest. CONCLUSION: The incidence in NSW and QLD is higher than previously published. The first postnatal day is a vulnerable period for newborns, who require close observation particularly during skin-to-skin contact. Development and implementation of guidelines for safe sleeping in hospital are needed. Collaboration between obstetricians, midwives, and pediatricians is essential to ensure safety of the newborn. PMID- 27384401 TI - STAT3 Represses Nitric Oxide Synthesis in Human Macrophages upon Mycobacterium tuberculosis Infection. AB - Mycobacterium tuberculosis is a successful intracellular pathogen. Numerous host innate immune responses signaling pathways are induced upon mycobacterium invasion, however their impact on M. tuberculosis replication is not fully understood. Here we reinvestigate the role of STAT3 specifically inside human macrophages shortly after M. tuberculosis uptake. We first show that STAT3 activation is mediated by IL-10 and occurs in M. tuberculosis infected cells as well as in bystander non-colonized cells. STAT3 activation results in the inhibition of IL-6, TNF-alpha, IFN-gamma and MIP-1beta. We further demonstrate that STAT3 represses iNOS expression and NO synthesis. Accordingly, the inhibition of STAT3 is detrimental for M. tuberculosis intracellular replication. Our study thus points out STAT3 as a key host factor for M. tuberculosis intracellular establishment in the early stages of macrophage infection. PMID- 27384404 TI - Recommendations for neonatologist performed echocardiography in Europe: Consensus Statement endorsed by European Society for Paediatric Research (ESPR) and European Society for Neonatology (ESN). PMID- 27384405 TI - Glandular breast tissue volume by magnetic resonance imaging in 100 healthy peripubertal girls: evaluation of clinical Tanner staging. AB - BACKGROUND: Appearance of glandular breast tissue may be difficult to distinguish from fat tissue by palpation, especially in obese girls. To our knowledge, validation of the clinical assessment of pubertal breast stages by magnetic resonance imaging (MRI) has never been performed. Our objective was to report normative data of glandular breast tissue volume and validate the clinical evaluation of pubertal breast staging by MRI of breast tissue and to evaluate circulating reproductive hormone levels and estrogen-dependent transabdominal ultrasound (TAUS) parameters as markers of glandular breast tissue. METHODS: Glandular breast tissue volume quantified by MRI and breast stage evaluation was performed in 100 healthy peripubertal girls. Circulating levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, and estradiol were measured by immunoassays. Ovarian volume, uterine volume, and endometrial thickness were assessed by TAUS. RESULTS: Glandular breast tissue volume was positively associated with Tanner stages (r = 0.858, P < 0.001). The sensitivity and specificity of breast palpation to detect presence of glandular breast tissue using MRI as gold standard were 96 and 95%, respectively. The best parameters to distinguish prepubertal girls from girls with breast development were: LH (area under the curve (AUC) by receiver operating characteristic analysis = 0.871), inhibin B (AUC = 0.847) and estradiol (AUC = 0.830). CONCLUSION: Clinical palpation reliably detects the presence of glandular breast tissue. PMID- 27384407 TI - The International Neonatal Consortium: collaborating to advance regulatory science for neonates. PMID- 27384406 TI - Renal epithelial miR-205 expression correlates with disease severity in a mouse model of congenital obstructive nephropathy. AB - BACKGROUND: Congenital obstructive nephropathy (CON) is a leading cause of pediatric chronic kidney disease (CKD). Despite optimal surgical and medical care, there is a high rate of CKD progression. Better understanding of molecular and cellular changes is needed to facilitate development of improved biomarkers and novel therapeutic approaches in CON. METHODS: The megabladder (mgb) mouse is an animal model of CKD with impaired bladder emptying, hydronephrosis, and progressive renal injury. In this study, we characterize a particular microRNA, miR-205, whose expression changes with the degree of hydronephrosis in the mgb(-/ ) kidney. RESULTS: Expression of miR-205 is progressively increased in the adult mgb(-/-) mouse with worsening severity of hydronephrosis. miR-205 expression is correlated with altered expression of cytokeratins and uroplakins, which are markers of cellular differentiation in urothelium. We describe the spatial pattern of miR-205 expression, including increased expression in renal urothelium and novel miR-205 expression in medullary collecting duct epithelium in the congenitally obstructed kidney. CONCLUSION: miR-205 is increased with severity of CON and CKD in the mgb(-/-) mouse and may regulate urothelial differentiation. PMID- 27384408 TI - Micro/Nanoparticle-Augmented Sonodynamic Therapy (SDT): Breaking the Depth Shallow of Photoactivation. AB - The fast development of photoactivation for cancer treatment provides an efficient photo-therapeutic strategy for cancer treatment, but traditional photodynamic or photothermal therapy suffers from the critical issue of low in vivo penetration depth of tissues. As a non-invasive therapeutic modality, sonodynamic therapy (SDT) can break the depth barrier of photoactivation because ultrasound has an intrinsically high tissue-penetration performance. Micro/nanoparticles can efficiently augment the SDT efficiency based on nanobiotechnology. The state-of-art of the representative achievements on micro/nanoparticle-enhanced SDT is summarized, and specific functions of micro/nanoparticles for SDT are discussed, from the different viewpoints of ultrasound medicine, material science and nanobiotechnology. Emphasis is put on the relationship of structure/composition-SDT performance of micro/nanoparticle based sonosensitizers. Three types of micro/nanoparticle-augmented SDT are discussed, including organic and inorganic sonosensitizers and micro/nanoparticle based but sonosensitizer-free strategies to enhance the SDT outcome. SDT-based synergistic cancer therapy augmented by micro/nanoparticles and their biosafety are also included. Some urgent critical issues and potential developments of micro/nanoparticle-augmented SDT for efficient cancer treatment are addressed. It is highly expected that micro/nanoparticle-augmented SDT will be quickly developed as a new and efficient therapeutic modality which will find practical applications in cancer treatment. At the same time, fundamental disciplines regarding materials science, chemistry, medicine and nanotechnology will be advanced. PMID- 27384409 TI - Buschke-Lowenstein tumor: Three pediatric cases. PMID- 27384410 TI - Differentiation between Polymyalgia Rheumatica (PMR) and Elderly-Onset Rheumatoid Arthritis Using 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography: Is Enthesitis a New Pathological Lesion in PMR? AB - BACKGROUND: It is difficult to differentiate polymyalgia rheumatica (PMR) from elderly-onset rheumatoid arthritis (EORA) in clinical practice. We compared FDG PET/CT findings between patients with PMR and those with EORA and extracted factors useful for differentiating the two disorders. METHODS: We compared abnormal FDG accumulation sites and maximum standardized uptake value (SUVmax) between 15 patients with PMR and 7 with EORA in whom FDG-PET/CT was performed. RESULTS: The proportion of patients in the PMR group with abnormal FDG accumulation at the following 9 sites on FDG-PET/CT was significantly higher than that in the EORA group: periarticular region of the scapulohumeral joint, enthesis of the pectineus muscle, vicinity of the enthesis of the rectus femoris muscle, lateral side of the greater trochanter, ischial tuberosity, hip joint, spinous process of the lower cervical vertebra, intervertebral joint of the lumbar vertebra, and spinous process of the lumbar vertebra. The PET/CT score was evaluated at 9 sites consisting of the abovementioned sites. The median score in the PMR group was 8, which was significantly higher than that of 0 in the EORA group (P = 0.0003). ROC curve analysis was performed with the PET/CT scores, and a score of 5 was shown to maximize the area under the ROC curve (sensitivity: 86.7%, specificity: 86.7%). CONCLUSIONS: FDG-PET/CT is useful for differentiating PMR from EORA. In patients with PMR, abnormal FDG accumulation was observed at the entheses, suggesting the presence of enthesitis in addition to bursitis and synovitis. PMID- 27384411 TI - Correction: Optimization of the All-D Peptide D3 for Abeta Oligomer Elimination. AB - [This corrects the article DOI: 10.1371/journal.pone.0153035.]. PMID- 27384412 TI - Quantification and reproducibility assessment of the regional brain T2 relaxation in naive rats at 7T. AB - PURPOSE: To measure the reproducibility of T2 relaxation and to determine the statistical power of T2 mapping in the rat brain as a characteristic of the baseline performance of the T2 relaxation as a potential biomarker of neurotoxicity. MATERIALS AND METHODS: Multislice multiecho spin-echo imaging was utilized to obtain the quantitative T2 maps in 138 naive rats at 7T. Images were skull-stripped and coregistered to the common anatomical reference. A full anatomical segmentation mask, which included all major brain structures, was created using the same reference T2 map. The overall variability map was also calculated from all T2 maps and the areas with arbitrarily high variability (coefficient of variation >25%) were excluded from the full segmentation mask to produce a trimmed mask. T2 maps were segmented using both these masks and statistical power analysis was conducted in all segmented areas. RESULTS: The coefficient of variation of T2 relaxation in different brain areas varied from 5.4% (cerebrospinal fluid) to 1.2% (cortex) when using a full segmentation mask. The use of a trimmed segmentation mask decreased the coefficient of variation in many areas, which ranged between 3.2% (inferior colliculi) and 1.2% (cortex) in this case. As revealed by statistical power analysis to detect 5% change with power of 0.8, the minimum number of observations needed for different areas ranged from 3 (cortex) to 8 (inferior colliculi) in the case of use of a trimmed segmentation mask. CONCLUSION: T2 relaxation is a very reproducible MRI parameter of the rat brain with high statistical power, which allows detecting very small changes in groups consisting of a minimal number of experimental animals. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:700-709. PMID- 27384415 TI - Wireless Hazard Badges to Detect Nerve-Agent Simulants. AB - Human exposure to hazardous chemicals can have adverse short- and long-term health effects. In this Communication, we have developed a single-use wearable hazard badge that dosimetrically detects diethylchlorophosphate (DCP), a model organophosphorous cholinesterase inhibitor simulant. Improved chemically actuated resonant devices (CARDs) are fabricated in a single step and unambiguously relate changes in chemiresistance to a wireless readout. To provide selective and readily manufacturable sensor elements for this platform, we developed an ionic liquid-mediated single walled carbon nanotube based chemidosimetric scheme with DCP limits of detection of 28 ppb. As a practical demonstration, an 8 h workday time weighted average equivalent exposure of 10 ppb DCP effects an irreversible change in smartphone readout. PMID- 27384414 TI - Psychosocial and Physiological Predictors of Mortality in Patients of Heart Failure: Independent Effects of Marital Status and C-Reactive Protein. AB - PURPOSE: Few studies have examined the interplay between psychosocial and physiological variables in prediction of mortality in heart failure (HF) patients. This study investigated the prospective influence of marital status, social support, depression, and C-reactive protein (CRP) on the mortality of patients with chronic HF. In addition, it examined whether there was a mediating relationship between social support and marital status and whether depression and inflammation influenced one another to predict mortality of HF patients. METHODS: The participants were 220 HF patients, among whom 48 were deceased over an average of 4.60 years. A number of psychosocial and biomedical variables were examined for their associations with mortality and their relationships between each other in hierarchical logistic regression analyses. RESULTS: After adjusting for New York Heart Association (NYHA) class, age, and gender, being unmarried predicted mortality (OR = 2.80, p = 0.004), whereas perceived social support did not. Higher CRP was not associated with depression, and it independently predicted mortality (OR = 1.92, p = 0.030). Depression predicted mortality only in the univariate analysis (OR = 1.02, p = 0.030), but the association was no longer significant either after removing somatic items or after adjusting for covariates. In the combined multivariate model, marital status (OR = 2.20, p = 0.047), CRP (OR = 1.91, p = 0.035), and NYHA class (OR = 2.41, p = 0.001) independently predicted mortality. CONCLUSIONS: Monitoring chronic HF patients who are unmarried, with elevated inflammation, or in higher NYHA class may help identify those at greater mortality risk to implement targeted intervention. PMID- 27384413 TI - Maternal gene-micronutrient interactions related to one-carbon metabolism and the risk of myelomeningocele among offspring. AB - BACKGROUND: Few studies have evaluated interactions between maternal genetic variation in 5,10-methylenetetrahydrofolate reductase (MTHFR) and micronutrient intake on the risk of myelomeningocele (MM) in offspring. Therefore, we sought to determine if the role of maternal MTHFR C677T and A1298C on MM risk is altered by maternal intake of micronutrients related to one-carbon metabolism. METHODS: The study consisted of 220 MM case-parent trios recruited from 1996 to 2006. A dietary questionnaire was used to obtain information on maternal dietary intake on eight micronutrients including folate and cobalamin. TaqMan assays were used to generate MTHFR C677T and A1298C genotypes. Log-linear models were used to evaluate the joint effects of maternal genotype and micronutrient intake dichotomized as at or above versus below the United States Recommended Dietary Allowance (US RDA) on MM. RESULTS: There was little evidence to suggest maternal MTHFR genotypes interacted with micronutrient intake to influence the risk of MM. For instance, the effect of MTHFR 677T was similar for mothers with cobalamin intake below US RDA (relative risk [RR] = 0.97) versus at or above US RDA cobalamin intake (RR = 0.81, interaction p = 0.87). However, some differences were noted. For example, the effect of MTHFR 1298C appeared to be different between those mothers below US RDA folate intake (RR = 0.98) versus those at or above US RDA folate intake (RR = 0.68), but the interaction was not statistically significant (interaction p = 0.27). CONCLUSION: There did not appear to be strong effects of maternal micronutrient intake on the role of maternal genetic polymorphisms in MTHFR C677T and A1298C on MM risk. Birth Defects Research 109:99 105, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27384416 TI - Cholinergic Antagonists Combined with Electrical Stimulation or Bladder Training Treatments for Overactive Bladder in Female Adults: A Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND AND OBJECTIVE: The therapeutic effects of cholinergic antagonists combined with non-drug therapy compared with cholinergic antagonist therapy alone for overactive bladder in adult women are unclear. Thus, we conducted a meta analysis of randomized controlled trials to compare the therapeutic effects of cholinergic antagonists plus non-drug therapy (electrical stimulation and bladder training) with cholinergic antagonist therapy alone among female overactive bladder patients. METHODS: Pertinent studies were identified by searching PubMed, Web of Science, and the Chinese Biological Medicine databases to May 31, 2016. Study-specific standardized mean differences were combined using fixed- or random effects models depending on whether significant heterogeneity was detected. RESULTS: Ten randomized controlled trials were identified. A total of 485 female overactive bladder patients were treated with the combined therapy and 497 were treated with the cholinergic antagonists alone. For the cholinergic antagonists combined with electrical stimulation treatment compared with cholinergic antagonist therapy alone, there were statistically significant reductions of average frequency of urination, incontinence, and urgency, with pooled standardized mean differences of -2.38, -1.32, and -0.87, respectively. There was also a statistically significant reduction of average frequency of urination (pooled standardized mean difference = - 0.30; 95 % confidence interval: -0.52 to -0.08) for the cholinergic antagonists combined with bladder training treatment compared with cholinergic antagonist therapy alone. CONCLUSION: This study indicated that female overactive bladder patients with cholinergic antagonists combined with electrical stimulation or bladder training treatment may lower the average frequency of urination, incontinence, and urgency when compared with those who received isolated drug therapy. PMID- 27384418 TI - Derivatization coupled to headspace programmed-temperature vaporizer gas chromatography with mass spectrometry for the determination of amino acids: Application to urine samples. AB - A new method based on headspace programmed-temperature vaporizer gas chromatography with mass spectrometry has been developed and validated for the determination of amino acids (alanine, sarcosine, ethylglycine, valine, leucine, and proline) in human urine samples. Derivatization with ethyl chloroformate was employed successfully to determine the amino acids. The derivatization reaction conditions as well as the variables of the headspace sampling were optimized. The existence of a matrix effect was checked and the analytical characteristics of the method were determined. The limits of detection were 0.15-2.89 mg/L, and the limits of quantification were 0.46-8.67 mg/L. The instrumental repeatability was 1.6-11.5%. The quantification of the amino acids in six urine samples from healthy subjects was performed with the method developed with the one-point standard additions protocol, with norleucine as the internal standard. PMID- 27384417 TI - Comprehensive MR Urography Protocol: Equally Good Diagnostic Performance and Enhanced Visibility of the Upper Urinary Tract Compared to Triple-Phase CT Urography. AB - OBJECTIVES: To prospectively compare the diagnostic performance and the visualization of the upper urinary tract (UUT) using a comprehensive 3.0T- magnetic resonance urography (MRU) protocol versus triple-phase computed tomography urography (CTU). METHODS: During the study period (January-2014 through December-2015), all consecutive patients in our tertiary university hospital scheduled by a urologist for CTU to exclude UUT malignancy were invited to participate. Diagnostic performance and visualization scores of 3.0T-MRU were compared to CTU using Wilcoxon matched-pairs test. RESULTS: Twenty patients (39 UUT excreting units) were evaluated. 3.0T-MRU and CTU achieved equal diagnostic performances. The benign etiology of seven UUT obstructions was clarified equally with both methods. Another two urinary tract malignant tumors and one benign extraurinary tumor were detected and confirmed. Diagnostic visualization was slightly better in the intrarenal cavity areas with CTU but worsened towards distal ureter. MRU showed consistently slightly better visualization of the ureter. In the comparison, full 100% visualizations were detected in all areas in 93.6% (with 3.0T-MRU) and 87.2% (with CTU) and >75% visualization in 100% (3.0T MRU) and 93.6% (CTU). Mean CTU effective radiation dose was 9.2 mSv. CONCLUSIONS: Comprehensive 3.0T-MRU is an accurate imaging modality achieving comparable performance with CTU; since it does not entail exposure to radiation, it has the potential to become the primary investigation technique in selected patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02606513. PMID- 27384419 TI - Plio-Pleistocene evolution of Bohai Basin (East Asia): demise of Bohai Paleolake and transition to marine environment. AB - The Bohai Basin was transformed to an inner shelf sea hundreds of thousands years ago. This youngest land-sea transition participated in the significant modification of the distribution of fresh water, sediment fluxes and climate in East Asia, and played an important role in the origin of the Asian marginal seas. Here we present the results of a magnetostratigraphic investigation and propose a conceptual model for the land-sea transition. Our findings indicate that the transition probably started several million years ago, from a fluvial system during the late Miocene and early Pliocene, to a lacustrine environment between the late Pliocene and Middle Pleistocene, and finally to a marine system in the late Pleistocene. Comparison of our results with previous research suggests that the Bohai Paleolake was initiated from the late Pliocene, was fully developed prior to ~1.0 Ma, and terminated around the late Middle Pleistocene. The Miaodao Islands formed the eastern "barrier" of the basin and since the Pliocene or earlier they played a significant role in blocking the lake water and sediments. They deformed from ~1.0 Ma, subsided significantly at ~0.3 Ma and completely by ~0.1 Ma, resulting in the maturation of the basin as an inner shelf sea. PMID- 27384420 TI - Extracranial Venous Drainage Pattern in Multiple Sclerosis and Healthy Controls: Application of the 2011 Diagnostic Criteria for Chronic Cerebrospinal Venous Insufficiency. AB - The etiology of multiple sclerosis (MS) is still largely unknown and it has been proposed that an impaired venous drainage from the central nervous system, defined as chronic cerebrospinal venous insufficiency (CCSVI), may play a role in this. We investigated the prevalence of extracranial venous drainage pattern alterations in a cohort of MS patients based on the 2011 revised diagnostic criteria for CCSVI. Thirty-nine MS patients and 18 healthy subjects underwent blinded extra-cranial venous echo-color Doppler sonography to reveal the presence of CCSVI. There was no statistically significant difference between MS patients and healthy controls regarding CCSVI prevalence (p value = 0.53). The results challenge the hypothesis that CCSVI plays a primary role in the pathogenesis of MS. PMID- 27384422 TI - Authors' reply to Gallagher and Winocour. PMID- 27384421 TI - Screening of Conditionally Reprogrammed Patient-Derived Carcinoma Cells Identifies ERCC3-MYC Interactions as a Target in Pancreatic Cancer. AB - PURPOSE: Even when diagnosed prior to metastasis, pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with almost 90% lethality, emphasizing the need for new therapies optimally targeting the tumors of individual patients. EXPERIMENTAL DESIGN: We first developed a panel of new physiologic models for study of PDAC, expanding surgical PDAC tumor samples in culture using short-term culture and conditional reprogramming with the Rho kinase inhibitor Y-27632, and creating matched patient-derived xenografts (PDX). These were evaluated for sensitivity to a large panel of clinical agents, and promising leads further evaluated mechanistically. RESULTS: Only a small minority of tested agents was cytotoxic in minimally passaged PDAC cultures in vitro Drugs interfering with protein turnover and transcription were among most cytotoxic. Among transcriptional repressors, triptolide, a covalent inhibitor of ERCC3, was most consistently effective in vitro and in vivo causing prolonged complete regression in multiple PDX models resistant to standard PDAC therapies. Importantly, triptolide showed superior activity in MYC-amplified PDX models and elicited rapid and profound depletion of the oncoprotein MYC, a transcriptional regulator. Expression of ERCC3 and MYC was interdependent in PDACs, and acquired resistance to triptolide depended on elevated ERCC3 and MYC expression. The Cancer Genome Atlas analysis indicates ERCC3 expression predicts poor prognosis, particularly in CDKN2A-null, highly proliferative tumors. CONCLUSIONS: This provides initial preclinical evidence for an essential role of MYC-ERCC3 interactions in PDAC, and suggests a new mechanistic approach for disruption of critical survival signaling in MYC-dependent cancers. Clin Cancer Res; 22(24); 6153-63. (c)2016 AACR. PMID- 27384423 TI - Pesticides are Associated with Allergic and Non-Allergic Wheeze among Male Farmers. AB - BACKGROUND: Growing evidence suggests that pesticide use may contribute to respiratory symptoms. OBJECTIVE: We evaluated the association of currently used pesticides with allergic and non-allergic wheeze among male farmers. METHODS: Using the 2005-2010 interview data of the Agricultural Health Study, a prospective study of farmers in North Carolina and Iowa, we evaluated the association between allergic and non-allergic wheeze and self-reported use of 78 specific pesticides, reported by >= 1% of the 22,134 men interviewed. We used polytomous regression models adjusted for age, BMI, state, smoking, and current asthma, as well as for days applying pesticides and days driving diesel tractors. We defined allergic wheeze as reporting both wheeze and doctor-diagnosed hay fever (n = 1,310, 6%) and non-allergic wheeze as reporting wheeze but not hay fever (n = 3,939, 18%); men without wheeze were the referent. RESULTS: In models evaluating current use of specific pesticides, 19 pesticides were significantly associated (p < 0.05) with allergic wheeze (18 positive, 1 negative) and 21 pesticides with non-allergic wheeze (19 positive, 2 negative); 11 pesticides were associated with both. Seven pesticides (herbicides: 2,4-D and simazine; insecticides: carbaryl, dimethoate, disulfoton, and zeta-cypermethrin; and fungicide pyraclostrobin) had significantly different associations for allergic and non-allergic wheeze. In exposure-response models with up to five exposure categories, we saw evidence of an exposure-response relationship for several pesticides including the commonly used herbicides 2,4-D and glyphosate, the insecticides permethrin and carbaryl, and the rodenticide warfarin. CONCLUSIONS: These results for farmers implicate several pesticides that are commonly used in agricultural and residential settings with adverse respiratory effects. PMID- 27384424 TI - Polygenic Risk of Psychosis and Ventral Striatal Activation During Reward Processing in Healthy Adolescents. AB - IMPORTANCE: Psychotic disorders are characterized by attenuated activity in the brain's valuation system in key reward processing areas, such as the ventral striatum (VS), as measured with functional magnetic resonance imaging. OBJECTIVE: To examine whether common risk variants for psychosis are associated with individual variation in the VS. DESIGN, SETTING, AND PARTICIPANTS: A cross sectional study of a large cohort of adolescents from the IMAGEN study (a European multicenter study of reinforcement sensitivity in adolescents) was performed from March 1, 2008, through December 31, 2011. Data analysis was conducted from October 1, 2015, to January 9, 2016. Polygenic risk profile scores (RPSs) for psychosis were generated for 1841 healthy adolescents. Sample size and characteristics varied across regression analyses, depending on mutual information available (N = 1524-1836). MAIN OUTCOMES AND MEASURES: Reward-related brain function was assessed with blood oxygen level dependency (BOLD) in the VS using the monetary incentive delay (MID) task, distinguishing reward anticipation and receipt. Behavioral impulsivity, IQ, MID task performance, and VS BOLD were regressed against psychosis RPS at 4 progressive P thresholds (P < .01, P < .05, P < .10, and P < .50 for RPS models 1-4, respectively). RESULTS: In a sample of 1841 healthy adolescents (mean age, 14.5 years; 906 boys and 935 girls), we replicated an association between increasing psychosis RPS and reduced IQ (matrix reasoning: corrected P = .003 for RPS model 2, 0.4% variance explained), supporting the validity of the psychosis RPS models. We also found a nominally significant association between increased psychosis RPS and reduced MID task performance (uncorrected P = .03 for RPS model 4, 0.2% variance explained). Our main finding was a positive association between psychosis RPS and VS BOLD during reward anticipation at all 4 psychosis RPS models and for 2 P thresholds for reward receipt (RPS models 1 and 3), correcting for the familywise error rate (0.8%-1.9% variance explained). CONCLUSIONS AND RELEVANCE: These findings support an association between psychosis RPS and VS BOLD in adolescents. Genetic risk for psychosis may shape an individual's response to rewarding stimuli. PMID- 27384425 TI - Study of Uridine 5'-Diphosphate (UDP)-Galactopyranose Mutase Using UDP-5 Fluorogalactopyranose as a Probe: Incubation Results and Mechanistic Implications. AB - Uridine 5'-diphosphate-5-fluorogalactopyranose (UDP-5F-Galp, 7) was synthesized, and its effect on UDP-Galp mutase (UGM) was investigated. UGM facilitated the hydrolysis of 7 to yield UDP and 5-oxogalactose (24), but no 11 was detected. (19)F NMR and trapping experiments demonstrated that the reaction involves the initial formation of a substrate-cofactor adduct followed by decomposition of the resulting C5 gem-fluorohydrin to generate a 5-oxo intermediate (10). The results support the current mechanistic proposal for UGM and suggest new directions for designing mechanism-based inhibitors. PMID- 27384426 TI - Mesenchymal Stromal Cells Protect Endothelial Cells from Cytotoxic T Lymphocyte Induced Lysis. AB - The integrity of the vasculature plays an important role in the success of allogeneic organ and haematopoietic stem cell transplantation. Endothelial cells (EC) have previously been shown to be the target of activated cytotoxic T lymphocytes (CTL) resulting in extensive cell lysis. Mesenchymal stromal cells (MSC) are multipotent cells which can be isolated from multiple sites, each demonstrating immunomodulatory capabilities. They are explored herein for their potential to protect EC from CTL-targeted lysis. CD8(+) T cells isolated from human PBMC were stimulated with mitotically inactive cells of a human microvascular endothelial cell line (CDC/EU.HMEC-1, further referred to as HMEC) for 7 days. Target HMEC were cultured in the presence or absence of MSC for 24 h before exposure to activated allogeneic CTL for 4 h. EC were then analysed for cytotoxic lysis by flow cytometry. Culture of HMEC with MSC in the efferent immune phase (24 h before the assay) led to a decrease in HMEC lysis. This lysis was determined to be MHC Class I restricted linked and further analysis suggested that MSC contact is important in abrogation of lysis, as protection is reduced where MSC are separated in transwell experiments. The efficacy of multiple sources of MSC was also confirmed, and the collaborative effect of MSC and the endothelium protective drug defibrotide were determined, with defibrotide enhancing the protection provided by MSC. These results support the use of MSC as an adjuvant cellular therapeutic in transplant medicine, alone or in conjunction with EC protective agents such as defibrotide. PMID- 27384428 TI - The Cultural Value of Older People's Experiences of Theater-making: A Review. AB - Purpose of the Study: Although a number of existing reviews document the health and social benefits of arts participation by older people, there are none which focus specifically on theater and drama. This article presents the findings of a study conducted as part of the UK's Arts and Humanities Research Council "Cultural Value Project." The 2-year (2013-2015) "Cultural Value Project" sought to make a major contribution to how we think about the value of arts and culture to individuals and to society. It made 72 awards: 19 critical reviews of existing bodies of research, 46 research development awards to carry out new research, and 7 expert workshop awards to facilitate discussions among academics and practitioners. Together, these awards explored the components of cultural value and the ways in which cultural value is evidenced and evaluated. Design and Methods: Following an extensive search of academic databases and E-mail requests via relevant organizations and networks, 77 publications formed the basis for our own critical review. Results: Our findings highlight the benefits and value of older people's theater and drama participation on health and well-being, group relationships, learning and creativity, and draw attention to the importance of the esthetic value and quality of older people's drama. Implications: Despite the recent surge of interest in this field (a third of the reviewed literature was published between 2010 and 2014), we suggest that there are multiple areas for further research. PMID- 27384427 TI - Pigment Epithelium Derived Factor Peptide Protects Murine Hepatocytes from Carbon Tetrachloride-Induced Injury. AB - Fibrogenesis is induced by repeated injury to the liver and reactive regeneration and leads eventually to liver cirrhosis. Pigment epithelium derived factor (PEDF) has been shown to prevent liver fibrosis induced by carbon tetrachloride (CCl4). A 44 amino acid domain of PEDF (44-mer) was found to have a protective effect against various insults to several cell types. In this study, we investigated the capability of synthetic 44-mer to protect against liver injury in mice and in primary cultured hepatocytes. Acute liver injury, induced by CCl4, was evident from histological changes, such as cell necrosis, inflammation and apoptosis, and a concomitant reduction of glutathione (GSH) and GSH redox enzyme activities in the liver. Intraperitoneal injection of the 44-mer into CCl4-treated mice abolished the induction of AST and ALT and markedly reduced histological signs of liver injury. The 44-mer treatment can reduce hepatic oxidative stress as evident from lower levels of lipid hydroperoxide, and higher levels of GSH. CCl4 caused a reduction of Bcl-xL, PEDF and PPARgamma, which was markedly restored by the 44 mer treatment. Consequently, the 44-mer suppressed liver fibrosis induced by repeated CCl4 injury. Furthermore, our observations in primary culture of rat hepatocytes showed that PEDF and the 44-mer protected primary rat hepatocytes against apoptosis induced by serum deprivation and TGF-beta1. PEDF/44-mer induced cell protective STAT3 phosphorylation. Pharmacological STAT3 inhibition prevented the antiapoptotic action of PEDF/44-mer. Among several PEDF receptor candidates that may be responsible for hepatocyte protection, we demonstrated that PNPLA2 was essential for PEDF/44-mer-mediated STAT3 phosphorylation and antiapoptotic activity by using siRNA to selectively knockdown PNPLA2. In conclusion, the PEDF 44-mer protects hepatocytes from single and repeated CCl4 injury. This protective effect may stem from strengthening the counter oxidative stress capacity and induction of hepatoprotective factors. PMID- 27384429 TI - Perineal Rectosigmoidectomy (Altemeier Procedure) as Treatment of Strangulated Rectal Prolapse. AB - Incarceration of a rectal prolapse is an unusual entity that represents a surgical emergency. Even more rarely, it becomes strangulated, requiring emergency surgery. When surgery becomes inevitable, the choice of procedure varies. A 57-year-old man who presented with strangulated rectal prolapse is described. The patient underwent emergency perineal proctosigmoidectomy, the Altemeier operation, combined with diverting loop sigmoid colostomy. The postoperative course was uneventful. After a 6-month follow-up, there was no recurrence, but the patient continued with fecal incontinence. This case underlines the importance of the Altemeier procedure as treatment in the patient with a strangulated prolapsed rectal segment. PMID- 27384430 TI - Tumor Biology Rather Than Surgical Technique Dictates Prognosis in Colorectal Cancer Liver Metastases. AB - INTRODUCTION: The interplay of tumor biology and surgical margin status after resection for colorectal liver metastasis (CRLM) remains controversial. Consequently, we sought to determine the impact of surgical margin status on overall survival (OS) stratified by KRAS mutational status. MATERIALS AND METHODS: Four hundred eighty-five patients with known KRAS mutational status were identified. Clinicopathologic and long-term survival data were collected and assessed. RESULTS: On pathology, most patients (n = 380; 78.3 %) had an R0 margin, while 105 (21.7 %) had an R1. Roughly two thirds of tumors were KRAS wild type (wtKRAS) (n = 307, 63.3 %), while 36.7 % (n = 178) had KRAS mutations (mutKRAS). Median and 5-year OS of the entire cohort was 65.8 months and 53.8 %, respectively. An R1 resection was associated with worse 5-year OS compared with R0 (42.4 % vs. 57.1 %; hazard ratio (HR) 1.82, 95 % CI 1.28-2.57; P = 0.001). After controlling for KRAS status, the survival benefit associated with an R0 resection persisted only among patients with wtKRAS tumors (HR 2.16, 95 % CI 1.42 3.30; P < 0.001). In contrast, surgical margin had no impact on OS among patients with mutKRAS tumors (5-year OS R0, 40.7 % vs. R1, 46.7 %; HR 1.34, 95 % CI 0.73 2.48; P = 0.348). CONCLUSION: The impact of margin status differed by KRAS mutation status. An R0 margin only provided a survival benefit to patients with wtKRAS tumors. Tumor biology and not surgical technique determined prognosis. PMID- 27384431 TI - Giant Gastric Gastrointestinal Stromal Tumor (GIST). AB - Gastrointestinal stromal tumors (GIST) represent 0.1-3 % of gastrointestinal malignancy. Surgery is the mainstay of treatment, but in high-risk tumors, imatinib can help to achieve better oncological outcomes. We present a rare case of a patient with gastric GIST with very aggressive evolution in a short period of time despite the use of neoadjuvant therapy with imatinib. PMID- 27384432 TI - Prognostic Role of Log Odds of Lymph Nodes After Resection of Pancreatic Head Cancer. AB - INTRODUCTION: Nodal status is a strong prognostic factor after resection of pancreatic cancer. The lymph node ratio (LNR) has been shown to be superior to the pN status in several studies. The role of log odds of the ratio between positive and negative nodes (LODDS) as a suggested new indicator of prognosis, however, has been hardly evaluated in pancreatic cancer. METHODS: Prognostic factors for overall survival after resection for cancer of the pancreatic head were evaluated in 409 patients from two institutions (prospectively maintained databases). The lymph node status, LNR, and LODDS were separately analyzed and independently compared in multivariate survival analysis. RESULTS: The median numbers of examined and positive lymph nodes were 16 and 2, respectively. Actuarial 3- and 5-year survival rates were 29 and 16 %. All three classifications of nodal disease significantly predicted survival in the entire group (n = 409), in patients with free resection margins (n = 297), and in patients with <12 examined nodes. In multivariate analysis, however, both LNR and LODDS were equally superior to the nodal status. In node-negative patients (n = 110), LODDS could not identify subgroups with different prognosis. CONCLUSION: Both LNR and LODDS are superior to the classical nodal status in predicting prognosis in resected pancreatic cancer. However, LODDS has not shown any advantage over LNR in our series, neither in the entire patient group nor in the subgroups with free margins, negative nodes or a low number of examined nodes. Therefore, the use of LODDS to predict the outcome after resection of pancreatic head cancer cannot be recommended. PMID- 27384433 TI - Evaluation of Electron Donation as a Mechanism for the Stabilisation of Chalcogenate-Protected Gold Nanoclusters. AB - Models based on Au(111) face have been extensively used to describe self assembled monolayers, as well nanoparticles and nanoclusters. However, for very small clusters (<2 nm), the chemisorption of ligands leads to surface reconstruction, making necessary the use of a more reliable model that is able to simulate the main electronic and geometrical features of these small systems. In this work, a simple model to describe the geometries and the metal-ligand bonding in chalcogenate-protected gold nanoclusters is proposed. Three different models with Aun+ and [XCH3 ]- (n=10, 15, 19, 22 and X=S, Se, Te) are used in this work. The obtained structures are in close agreement not only with the available crystallographic data, but also with much more expensive computational procedures, confirming that the proposed models are robust enough to describe the metal-ligand bonding. The results reveal that the Au-X distances are dependent on both the nature of the chalcogen and the coordination mode. The shortest Au-X distances are observed in the face-centred cubic mode, indicating that the central gold atom seems to play a role in determining the adsorption strength. The proposed models show unambiguously chalcogen->cluster sigma-donation, as supported by energy decomposition analysis coupled with the natural orbitals for chemical valence and natural bond orbital analyses. In all cases, the metal ligand interactions are characterised as being more covalent than electrostatic. PMID- 27384435 TI - Outcome of Rehabilitation and Swallowing Therapy after Percutaneous Endoscopic Gastrostomy in Dysphagia Patients. AB - The objective of this study was to investigate the outcomes of rehabilitation (with swallowing therapy) after percutaneous endoscopic gastrostomy (PEG) in patients with neurogenic dysphagia. Forty-seven patients (29 males and 18 females) who were transferred to the rehabilitation ward of our hospital after receiving PEG tube placements during a 5-year period were enrolled in this study. Patients' demographic data, comorbidities, nutritional statuses, and laboratory biomarkers before the PEG procedure were collected. Rehabilitation (with swallowing therapy) outcomes such as changes in Functional Independence Measure (FIM) and dysphagia grade (using Fujishima's classification) were evaluated. Significant improvements in FIM scores and dysphagia grades after rehabilitation therapy were observed. Twenty-seven patients (57.4 %) were discharged with some oral intake and 10 patients (21.3%) were discharged PEG-free (defined as the PEG tube not being used or removed). Factors associated with being discharged with some oral intake were increase in FIM score (adjusted OR 1.10, 95 % CI 1.02-1.19) and higher baseline dysphagia grade (adjusted OR 1.88, 95 % CI 1.04-3.39). Factors associated with being discharged PEG-free were longer rehabilitation period (OR 1.03, 95 % CI 1.01-1.04), absence of respiratory disorders (OR 0.12, 95 % CI 0.03-0.35), and increase in FIM score (OR 1.17, 95 % CI 1.08-1.28). Changes in dysphagia grade were significantly correlated with changes in FIM score (r 2 = 0.46, p < 0.0001), indicating that improvement of FIM scores through general rehabilitation therapy may play an important role in the treatment of dysphagia. PMID- 27384436 TI - An Epidemiologic Study on Ageing and Dysphagia in the Acute Care Geriatric Hospitalized Population: A Replication and Continuation Study. AB - United States census data project dramatic increases in the geriatric population ageing demographics by 2060 with concomitant health-care consequences. The purpose of this replication and continuation study was to collect new 2014 demographic data relative to ageing, swallow evaluation referral rates, and oral feeding status in geriatric-hospitalized patients for comparison with published data from 2000 to 2007. This was a planned data acquisition study of consecutive hospitalized patients referred for swallow assessments. Swallow evaluation referral rates for 2014 were described according to inpatient discharges, age range 60-105 years grouped by decade, gender, admitting diagnostic category, results of swallow evaluations, and oral feeding status. Determination of aspiration risk status was made with the Yale Swallow Protocol and diagnosis of dysphagia made with fiberoptic endoscopic evaluation of swallowing (FEES). There were 1348 referrals and 961 patients >=60 years of age participated. Overall swallow evaluation referral rates increased an average of 63 % between the comparison years 2007 and 2014 with consistent increases corresponding to the decades, i.e., 60-69 (46 %), 70-79 (68 %), 80-89 (53 %), and 90+ (222 %). A total of 75 % of participants resumed oral alimentation and oral medications. Swallow evaluation referral rates increased by 63 % for 60-90+ year-old acute care geriatric-hospitalized participants despite only a 23 % increase in inpatient discharges for the years 2007 versus 2014. This corroborated previously reported increases for individual years from 2000 to 2007. For timely, safe, and successful initiation of oral alimentation, it is important to perform a reliable swallow screen for aspiration risk assessment with the Yale Swallow Protocol and, if failed, instrumental testing with FEES. More dysphagia specialists are needed through 2060 and beyond due to projections of continued population ageing resulting in ever increasing referral rates for swallow assessments. PMID- 27384434 TI - MicroRNAs, heart failure, and aging: potential interactions with skeletal muscle. AB - MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by targeting mRNAs for degradation or translational repression. MiRNAs can be expressed tissue specifically and are altered in response to various physiological conditions. It has recently been shown that miRNAs are released into the circulation, potentially for the purpose of communicating with distant tissues. This manuscript discusses miRNA alterations in cardiac muscle and the circulation during heart failure, a prevalent and costly public health issue. A potential mechanism for how skeletal muscle maladaptations during heart failure could be mediated by myocardium-derived miRNAs released to the circulation is presented. An overview of miRNA alterations in skeletal muscle during the ubiquitous process of aging and perspectives on miRNA interactions during heart failure are also provided. PMID- 27384437 TI - Hydrogen Doped Metal Oxide Semiconductors with Exceptional and Tunable Localized Surface Plasmon Resonances. AB - Heavily doped semiconductors have recently emerged as a remarkable class of plasmonic alternative to conventional noble metals; however, controlled manipulation of their surface plasmon bands toward short wavelengths, especially in the visible light spectrum, still remains a challenge. Here we demonstrate that hydrogen doped given MoO3 and WO3 via a facile H-spillover approach, namely, hydrogen bronzes, exhibit strong localized surface plasmon resonances in the visible light region. Through variation of their stoichiometric compositions, tunable plasmon resonances could be observed in a wide range, which hinge upon the reduction temperatures, metal species, the nature and the size of metal oxide supports in the synthetic H2 reduction process as well as oxidation treatment in the postsynthetic process. Density functional theory calculations unravel that the intercalation of hydrogen atoms into the given host structures yields appreciable delocalized electrons, enabling their plasmonic properties. The plasmonic hybrids show potentials in heterogeneous catalysis, in which visible light irradiation enhanced catalytic performance toward p-nitrophenol reduction relative to dark condition. Our findings provide direct evidence for achieving plasmon resonances in hydrogen doped metal oxide semiconductors, and may allow large-scale applications with low-price and earth-abundant elements. PMID- 27384439 TI - Two different KIT mutations may lead to different responses to imatinib in metastatic gastrointestinal stromal tumor. PMID- 27384438 TI - Clinical manifestations of autoimmune disease-related non-Hodgkin lymphoma: a Korean single-center, retrospective clinical study. AB - BACKGROUND/AIMS: Recently, large cohort studies regarding associations between autoimmune disease and lymphomas have been reported in a few Western countries. However, Asian data concerning autoimmune-related lymphomas are limited. Therefore, we evaluated the clinical characteristics and prognostic factors of patients with autoimmune disease-related non-Hodgkin lymphoma (NHL) in a single center in Korea. METHODS: We analyzed the data from 11 patients with autoimmune related NHL. Patients were categorized into two groups, those with rheumatoid arthritis (RA) and those with non-RA-related NHL. Then patients were re categorized into a group with methotrexate (MTX) usage and a MTX non-usage group. Histological subtype, MTX duration, autoimmune disease duration, treatment modalities, and other data were collected and analyzed. RESULTS: Our study revealed that older RA patients have a greater likelihood of occurrence of NHL (p = 0.042). We confirmed that MTX duration and cumulative dose of MTX have no significant correlation with autoimmune disease and NHL (p = 0.073). In the management of autoimmune disease-related NHL, all patients were directly treated with systemic chemotherapy instead of employing a wait and watch approach. Overall survival (OS) and progression-free survival (PFS) in all autoimmune disease-related NHL were 100% and 87.5%, with no treatment-related mortality during the 2-year follow-up period of our study. CONCLUSIONS: Our study suggests that patients with RA-NHL are characterized by older age at onset compared to those with non-RA-NHL. Also considering of OS and PFS, intensive treatment strategy instead of delayed watchful managements may be required for autoimmune disease-related NHL including of old age group. PMID- 27384440 TI - Integrative Analysis of Subcellular Quantitative Proteomics Studies Reveals Functional Cytoskeleton Membrane-Lipid Raft Interactions in Cancer. AB - Lipid rafts are dynamic membrane microdomains that orchestrate molecular interactions and are implicated in cancer development. To understand the functions of lipid rafts in cancer, we performed an integrated analysis of quantitative lipid raft proteomics data sets modeling progression in breast cancer, melanoma, and renal cell carcinoma. This analysis revealed that cancer development is associated with increased membrane raft-cytoskeleton interactions, with ~40% of elevated lipid raft proteins being cytoskeletal components. Previous studies suggest a potential functional role for the raft-cytoskeleton in the action of the putative tumor suppressors PTRF/Cavin-1 and Merlin. To extend the observation, we examined lipid raft proteome modulation by an unrelated tumor suppressor opioid binding protein cell-adhesion molecule (OPCML) in ovarian cancer SKOV3 cells. In agreement with the other model systems, quantitative proteomics revealed that 39% of OPCML-depleted lipid raft proteins are cytoskeletal components, with microfilaments and intermediate filaments specifically down-regulated. Furthermore, protein-protein interaction network and simulation analysis showed significantly higher interactions among cancer raft proteins compared with general human raft proteins. Collectively, these results suggest increased cytoskeleton-mediated stabilization of lipid raft domains with greater molecular interactions as a common, functional, and reversible feature of cancer cells. PMID- 27384441 TI - Taxonomic and Phylogenetic Determinants of Functional Composition of Bolivian Bat Assemblages. AB - Understanding diversity patterns and the potential mechanisms driving them is a fundamental goal in ecology. Examination of different dimensions of biodiversity can provide insights into the relative importance of different processes acting upon biotas to shape communities. Unfortunately, patterns of diversity are still poorly understood in hyper-diverse tropical countries. Here, we assess spatial variation of taxonomic, functional and phylogenetic diversity of bat assemblages in one of the least studied Neotropical countries, Bolivia, and determine whether changes in biodiversity are explained by the replacement of species or functional groups, or by differences in richness (i.e., gain or loss of species or functional groups). Further, we evaluate the contribution of phylogenetic and taxonomic changes in the resulting patterns of functional diversity of bats. Using well-sampled assemblages from published studies we examine noctilionoid bats at ten study sites across five ecoregions in Bolivia. Bat assemblages differed from each other in all dimensions of biodiversity considered; however, diversity patterns for each dimension were likely structured by different mechanisms. Within ecoregions, differences were largely explained by species richness, suggesting that the gain or loss of species or functional groups (as opposed to replacement) was driving dissimilarity patterns. Overall, our results suggest that whereas evolutionary processes (i.e., historical connection and dispersal routes across Bolivia) create a template of diversity patterns across the country, ecological mechanisms modify these templates, decoupling the observed patterns of functional, taxonomic and phylogenetic diversity in Bolivian bats. Our results suggests that elevation represents an important source of variability among diversity patterns for each dimension of diversity considered. Further, we found that neither phylogenetic nor taxonomic diversity can fully account for patterns of functional diversity, highlighting the need for examining different dimensions of biodiversity of bats in hyperdiverse ecosystems. PMID- 27384442 TI - Ionic Liquid-Derived Imidazolium Cation Linkers for the Layer-by-Layer Assembly of Polyoxometalate-MWCNT Composite Electrodes with High Power Capability. AB - Imidazolium cations derived from ionic liquids were demonstrated as effective linker molecules for the layer-by-layer (LbL) deposition of polyoxometalates (POMs) to increase the charge storage of multi-walled carbon nanotube (MWCNT) electrodes. MWCNTs modified with GeMo12O40(4-) (GeMo12) via an imidazolium cation linker demonstrated highly reversible redox reactions and a capacitance of 84 F cm(-3), close to 4 times larger than bare CNT. Compared to CNT-GeMo12 composites fabricated with a conventional polyelectrolyte linker poly(diallyldimethylammonium chloride), (PDDA), the imidazolium cations resulted in lower POM loading, but higher conductivity and in turn superior performance at fast charge-discharge conditions. A polymerized imidazolium linker (PIL) was also synthesized based on the ethyl-vinyl-imidazolium monomer. CNT-GeMo12 composites fabricated with this PIL achieved high POM loading comparable to PDDA, while still maintaining the good conductivity and high rate capabilities shown by the monomer imidazolium units. The high conductivity imparted by the PIL is especially valuable for the fabrication of multilayer POM composites. Dual-layer GeMo12 O40(4-)-SiMo12O40(4-) (GeMo12-SiMo12) electrodes built with this PIL demonstrated a combined contribution of the individual POMs resulting in a capacitance of 191 F cm(-3), over nine times larger than bare MWCNT. The PIL dual layer composites also maintained 72% of this capacitance at a fast rate of 2 V s( 1), compared to just over 50% retention for similar electrodes fabricated with PDDA. PMID- 27384443 TI - Genomics and pharmacogenomics of sepsis: so close and yet so far. AB - Sapru et al. show in this issue of Critical Care that variants of thrombomodulin and the endothelial protein C receptor, but not protein C, are associated with mortality and organ dysfunction (ventilation-free and organ failure-free days) in ARDS. Hundreds of gene variants have been found prognostic in sepsis. However, none of these prognostic genomic biomarkers are used clinically. Predictive biomarker discovery (pharmacogenomics) usually follows a candidate gene approach, utilizing knowledge of drug pathways. Pharmacogenomics could be applied to enhance efficacy and safety of drugs used for treatment of sepsis (e.g., norepinephrine, epinephrine, vasopressin, and corticosteroids). Pharmacogenomics can enhance drug development in sepsis, which is very important because there is no approved drug for sepsis. Pharmacogenomics biomarkers must pass three milestones: scientific, regulatory, and commercial. Huge challenges remain but great opportunities for pharmacogenomics of sepsis are on the horizon. PMID- 27384444 TI - Regional Differences in Hepatitis C Treatment with Peginterferon and Ribavirin in Japan in Both Genotype 1 and Genotype 2: A Retrospective Cohort Study. AB - There has been no report on the genotype-dependent regional, especially prefectural, differences in hepatitis C treatment in Japan. We conducted a retrospective cohort study using the nationwide database. The registration period of the database was from December 2009 to April 2013. Individuals with chronic hepatitis C were identified from the database. The sustained virologic response (SVR) rates in each prefecture were calculated stratified by genotype. Confounding variables were identified using stepwise logistic regression analysis. The range of the point estimate of the adjusted odds ratio explained prefectural differences in treatment outcomes. During the registration period, 36 prefectures registered cases to the database. A total of 16349 cases were registered and 11653 cases were included in the analysis. The mean age was 57.9+/ 10.5 years; 7950 (68.2%) had hepatitis C virus (HCV) genotype 1 and 3703 (31.8%) had HCV genotype 2. The range in SVR rates was 30.0 to 63.0% for genotype 1 and 55.0 to 100.0% for genotype 2. In the multivariate analysis, the ranges of the adjusted odds ratio of each prefecture were 0.658 to 2.125 for genotype 1 and 0.364 to 2.630 for genotype 2. Our results suggest that regional, particularly prefectural, differences in chronic hepatitis C treatment with peg-interferon (IFN) and ribavirin (RBV) exist in Japan and that these regional differences may similarly exist both in HCV genotypes 1 and 2. Additional studies using these methods, considering medical situations in each prefecture and new treatments regimens, could greatly contribute to improving and standardizing chronic hepatitis C treatment. PMID- 27384446 TI - Gamma glutamyl transferase 'To be or not to be' a liver function test? PMID- 27384447 TI - Association of Multiple Melanocytic Naevi with Education, Sex and Skin Type. A Northern Finland Birth Cohort 1966 Study with 46 Years Follow-up. AB - Having multiple melanocytic naevi (< 50 naevi) is one of the strongest risk factors for melanoma. However, the epidemiology in adults is unclear. This comprehensive dermatological status investigation of 1,932 birth-cohort study cases aged 46 years analysed the prevalence of multiple melanocytic naevi and their association with sex, socioeconomic status (education) in childhood and adulthood, skin type and sunbathing habits. The prevalence of multiple melanocytic naevi was 11.6% (223/1,930). Higher education (odds ratio (OR) 2.11, 95% confidence interval (95% CI) 1.51-2.96), male sex (OR 1.48, 95% CI 1.07 2.06), sun-sensitive skin type (OR 2.09, 95% CI 1.34-3.27) and regular use of sunscreen (OR 2.03, 95% CI 1.23-3.37) were associated with increased risk of multiple naevi. Inflammatory skin diseases decreased (OR 0.49, 95 CI% 0.33-0.72) the risk of multiple naevi. In conclusion, several risk factors were found for multiple naevi among adults living in high latitudes, in Northern Finland. PMID- 27384445 TI - Dipeptidyl peptidase-4 inhibitors and fracture risk: an updated meta-analysis of randomized clinical trials. AB - Data on the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on fracture risk are conflicting. Here, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effects of DPP-4 inhibitors. Electronic databases were searched for relevant published articles, and unpublished studies presented at ClinicalTrials.gov were searched for relevant clinical data. Eligible studies included prospective randomized trials evaluating DPP-4 inhibitors versus placebo or other anti-diabetic medications in patients with type 2 diabetes. Study quality was determined using Jadad scores. Statistical analyses were performed to calculate the risk ratios (RRs) and 95% confidence intervals (CIs) using fixed-effects models. There were 62 eligible RCTs with 62,206 participants, including 33,452 patients treated with DPP-4 inhibitors. The number of fractures was 364 in the exposed group and 358 in the control group. The overall risk of fracture did not differ between patients exposed to DPP-4 inhibitors and controls (RR, 0.95; 95% CI, 0.83-1.10; P = 0.50). The results were consistent across subgroups defined by type of DPP-4 inhibitor, type of control, and length of follow-up. The study showed that DPP-4 inhibitor use does not modify the risk of bone fracture compared with placebo or other anti diabetic medications in patients with type 2 diabetes. PMID- 27384448 TI - Novel functional hepatitis C virus glycoprotein isolates identified using an optimized viral pseudotype entry assay. AB - Retrovirus pseudotypes are a highly tractable model used to study the entry pathways of enveloped viruses. This model has been extensively applied to the study of the hepatitis C virus (HCV) entry pathway, preclinical screening of antiviral antibodies and for assessing the phenotype of patient-derived viruses using HCV pseudoparticles (HCVpp) possessing the HCV E1 and E2 glycoproteins. However, not all patient-isolated clones produce particles that are infectious in this model. This study investigated factors that might limit phenotyping of patient-isolated HCV glycoproteins. Genetically related HCV glycoproteins from quasispecies in individual patients were discovered to behave very differently in this entry model. Empirical optimization of the ratio of packaging construct and glycoprotein-encoding plasmid was required for successful HCVpp genesis for different clones. The selection of retroviral packaging construct also influenced the function of HCV pseudoparticles. Some glycoprotein constructs tolerated a wide range of assay parameters, while others were much more sensitive to alterations. Furthermore, glycoproteins previously characterized as unable to mediate entry were found to be functional. These findings were validated using chimeric cell-cultured HCV bearing these glycoproteins. Using the same empirical approach we demonstrated that generation of infectious ebolavirus pseudoviruses (EBOVpv) was also sensitive to the amount and ratio of plasmids used, and that protocols for optimal production of these pseudoviruses are dependent on the exact virus glycoprotein construct. These findings demonstrate that it is crucial for studies utilizing pseudoviruses to conduct empirical optimization of pseudotype production for each specific glycoprotein sequence to achieve optimal titres and facilitate accurate phenotyping. PMID- 27384450 TI - SF5-Enolates in Ti(IV)-Mediated Aldol Reactions. AB - The F...Ti bonding in the transition structures determines high trans- and syn diastereoselectivities for aldol reactions of SF5-acetates with aldehydes in the presence of TiCl4 in the non-nucleophilic solvent CH2Cl2. Such bonding is canceled in nucleophilic solvents where opposite cis-stereochemistry is observed. The potential of thus obtained stereoisomeric SF5-aryl acrylates as dipolarophiles in the preparation of SF5-containing heterocycles is demonstrated. PMID- 27384449 TI - Dual anti-neutrophil cytoplasmic antibody-related pauci-immune crescentic glomerulonephritis in a patient with Sjogren's syndrome. AB - Sjogren's syndrome is an autoimmune disease that primarily affects exocrine glands. Renal involvement of Sjogren's syndrome may lead to tubulointerstitial disease, whereas secondary glomerulopathies such as anti-neutrophil cytoplasmic antibody (ANCA)-related pauci-immune crescentic glomerulonephritis are rarely observed. In addition, crescent glomerulonephritis that is simultaneously positive for both myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA has never been reported in Sjogren's syndrome. Here, we report a case of pauci-immune crescentic glomerulonephritis exhibiting positivity for both MPO- and PR3-ANCAs in a patient with primary Sjogren's syndrome. A 71-year-old female was hospitalized for cough, blood-tinged sputum, and dyspnea two weeks after diagnosis with Sjogren's syndrome. On admission, serum anti-nuclear antibody, anti-Ro/SS-A antibody, MPO-ANCA, and PR3-ANCA were all positive, and serum blood urea nitrogen and creatinine (Cr) levels were 42.7 and 2.9 mg/dL, respectively. On the seventh day of hospitalization, the patient's serum Cr level was 5.7 mg/dL, indicating rapidly progressive glomerulonephritis. Renal biopsy resulted in the diagnosis of ANCA-related pauci-immune crescentic glomerulonephritis, for which intravenous methylprednisolone (7 mg/kg/day) was administered for three consecutive days, followed by combination therapy with oral prednisolone (1 mg/kg/day) and intravenous cyclophosphamide (500 mg/m(2)). The patient was positive in the Schirmer's I test, and a salivary gland biopsy showed sialadenitis with lympho-plasmacytic infiltrations. On day 28 of hospitalization, the patient was discharged after amelioration of respiratory symptoms and azotemia. At 6 months after discharge, the patient continued to receive appropriate daily medications and was negative for both MPO- and PR3-ANCAs, with a slight elevation in serum Cr levels. PMID- 27384451 TI - [Not Available]. PMID- 27384452 TI - [Not Available]. AB - . Efficacy of splint with heel off-loaded in children with lower limbs plaster cast. Randomised open label trial. INTRODUCTION: Plasters cast are medical devices widely used in paediatric orthopaedics; however, few studies have addressed the occurrence and prevention of device-related complications. AIM: To evaluate whether positioning a custom made splint with heel off-loaded, would relieve pain, reduce care interventions, the materials to maintain heel unloading position and, at the same time, improve comfort and reduce pressure sores in children with lower limb plaster. METHODS: Children enrolled in the study were randomised to splint, provided with a custom made splint positioned underneath the lower limb plaster after surgery; in the second group (control) the plaster position was maintained with cushions. RESULTS: A total of 57 children were enrolled from November 2014 to August 2015, 29 in the treatment group (50.8%) and 28 in the control group (49.2%). Pain median levels were 4 (splint) vs. 5 (control) p=ns; mean number of care intervention was 2.1 (splint) vs. 5.2 (control) p<0.0005; materials used were 1.3 (splint) vs. 2.8 (control) p<0.0005; perceived comfort was 8.9 (splint) vs. 7.6 (control) p<0.001. A difference in the total number of pressure sores was observed with 1 case in the splint group vs. 5 cases in the control group RR 0.21 (IC 95% -1.88-2.29; P 0.079). CONCLUSIONS: The use of splint is effective in reducing care intervention the use of other materials and in improving comfort, but not in relieving pain. PMID- 27384453 TI - [Not Available]. AB - . Systems for the assessment of patients' complexity: a narrative review of the literature. INTRODUCTION: An effective and efficient caseload management ensures that patients receive the right care by the right person at the right time. Several systems are used in Italy to measure patients' complexity. AIM: To describe and compare the characteristics of the systems for measuring patients' complexity, used in Italy from 1994 to 2015. METHODS: A search was conducted on PubMed, CINAHL, Medline, Cochrane Library, and on Google, with the same key words. Systems dedicated to paediatric and intensive care patients were not included. The variables used to define complexity were classified according to 4 dimensions of the Italian model of Complexity of Nursing care (autonomy/dependence, stability/instability; comprehension and choice; context). RESULTS: Eight systems were identified, each using a different set and number of variables to define patients' complexity. For 5 systems the most influential dimension on the final score was the autonomy/dependence (from 74% to 34% of the final score). The Caring professional method (MAP), the Assessment on Nursing Intensity and clinical Complexity (IACC) and the Nursing Assessment of Complexity of Care (Per.V. In.Ca.) assign an higher score to the clinical stability/instability dimension. The dimension that contributes less to the final score is the Comprehension and choice (33% for one system but no more than 11-20% for all the others) and Context (from 0 to 30%). CONCLUSIONS: The systems are evolving from an assessment of nursing activities to the assessment of patients' conditions. The informatization of these systems will offer a valuable support to the definition of the right caring mix. PMID- 27384454 TI - [Not Available]. AB - . Mixed methods designs: an innovative methodological approach for nursing research. The mixed method research designs (MM) combine qualitative and quantitative approaches in the research process, in a single study or series of studies. Their use can provide a wider understanding of multifaceted phenomena. This article presents a general overview of the structure and design of MM to spread this approach in the Italian nursing research community. The MM designs most commonly used in the nursing field are the convergent parallel design, the sequential explanatory design, the exploratory sequential design and the embedded design. For each method a research example is presented. The use of MM can be an added value to improve clinical practices as, through the integration of qualitative and quantitative methods, researchers can better assess complex phenomena typical of nursing. PMID- 27384455 TI - [Not Available]. PMID- 27384456 TI - [Not Available]. PMID- 27384457 TI - [Not Available]. PMID- 27384458 TI - Fidgetin-like 1 is a ciliogenesis-inhibitory centrosome protein. AB - Fidgetin-like 1 (FIGL-1) is a homolog of fidgetin, an AAA protein that was identified as the protein encoded by the gene mutated in fidget mice. Because the phenotypes of fidget mice are reminiscent of the phenotypes of ciliopathy diseases, and because fidgetin has microtubule-severing activity, we hypothesize that these proteins participate in cilia-related processes. Indeed, overexpression of FIGL-1 interfered with ciliogenesis in cultured cells. In particular, overexpressed FIGL-1 strongly accumulated at the centrosome, and, when highly expressed, perturbed the localization of centrosomal proteins such as pericentrin, CP110, and centrin. Using a polyclonal antibody against human FIGL 1, we found that endogenous FIGL-1 localized preferentially around the mother centriole. Consistently, depletion of FIGL-1 by shRNA treatment enhanced ciliogenesis in HEK293T cells. By checking the integrity of the cytoplasmic microtubule network in FIGL-1-overexpressing cells, we found that FIGL-1 probably has microtubule-severing activity, as suggested by its sequence homology with other microtubule-severing proteins. Furthermore, we showed that overexpression of FIGL-1 in zebrafish embryo decreased the length of cilia and perturbed the heart laterality. Taken together, these results demonstrate that FIGL-1 is a new centrosomal protein and inhibits ciliogenesis. These results extend the already long list of centrosomal proteins and provide new insights into the regulation of ciliogenesis. PMID- 27384459 TI - Time-resolved dosimetric verification of respiratory-gated radiotherapy exposures using a high-resolution 2D ionisation chamber array. AB - The aim of this work was to track and verify the delivery of respiratory-gated irradiations, performed with three versions of TrueBeam linac, using a novel phantom arrangement that combined the OCTAVIUS((r)) SRS 1000 array with a moving platform. The platform was programmed to generate sinusoidal motion of the array. This motion was tracked using the real-time position management (RPM) system and four amplitude gating options were employed to interrupt MV beam delivery when the platform was not located within set limits. Time-resolved spatial information extracted from analysis of x-ray fluences measured by the array was compared to the programmed motion of the platform and to the trace recorded by the RPM system during the delivery of the x-ray field. Temporal data recorded by the phantom and the RPM system were validated against trajectory log files, recorded by the linac during the irradiation, as well as oscilloscope waveforms recorded from the linac target signal. Gamma analysis was employed to compare time-integrated 2D x-ray dose fluences with theoretical fluences derived from the probability density function for each of the gating settings applied, where gamma criteria of 2%/2 mm, 1%/1 mm and 0.5%/0.5 mm were used to evaluate the limitations of the RPM system. Excellent agreement was observed in the analysis of spatial information extracted from the SRS 1000 array measurements. Comparisons of the average platform position with the expected position indicated absolute deviations of <0.5 mm for all four gating settings. Differences were observed when comparing time-resolved beam-on data stored in the RPM files and trajectory logs to the true target signal waveforms. Trajectory log files underestimated the cycle time between consecutive beam-on windows by 10.0 +/- 0.8 ms. All measured fluences achieved 100% pass-rates using gamma criteria of 2%/2 mm and 50% of the fluences achieved pass-rates >90% when criteria of 0.5%/0.5 mm were used. Results using this novel phantom arrangement indicate that the RPM system is capable of accurately gating x-ray exposure during the delivery of a fixed-field treatment beam. PMID- 27384460 TI - Meta-signature of mutated genes in gallbladder cancer: evidence based high throughput screening assays. PMID- 27384461 TI - Pulmonary hypertension and pregnancy outcomes: data from the Registry Of Pregnancy and Cardiac Disease (ROPAC) of the European Society of Cardiology. AB - AIMS: To describe the outcomes of pregnancy in women with pulmonary hypertension. METHODS AND RESULTS: In 2007 the European Registry on Pregnancy and Heart Disease was initiated by the European Society of Cardiology. Consecutive patients with all forms of cardiovascular disease, presenting with pregnancy, were enrolled with the aim of investigating the pregnancy outcomes. This subgroup of the cohort included 151 women with pulmonary hypertension (PH) either diagnosed by right heart catheterization or diagnosed as possible PH by echocardiographic signs, with 26% having pulmonary arterial hypertension (PAH), in three subgroups: idiopathic (iPAH), associated with congenital heart disease (CHD-PAH), or associated with other disease (oPAH), and 74% having PH caused by left heart disease (LHD-PH, n = 112). Maternal mean age was 29.2 +/- 5.6 years and 37% were nulliparous. Right ventricular systolic pressure was <50 mmHg in 59.6% of patients, 50-70 mmHg in 28.5% and >70 mmHg in 11.9%. In more than 75% of patients, the diagnosis of PH had been made before pregnancy. Maternal death up to 1 week after delivery occurred in five patients (3.3%), with another two out of 78 patients who presented for follow-up (2.6%), dying within 6 months after delivery. The highest mortality was found in iPAH (3/7, 43%). During pregnancy, heart failure occurred in 27%. Caesarean section was performed in 63.4% (23.9% as emergency). Therapeutic abortion was performed in 4.0%. Complications included miscarriage (5.6%), fetal mortality (2%), premature delivery (21.7%), low birth weight (19.0%), and neonatal mortality (0.7%). CONCLUSION: Mortality in this group of patients with various forms of PH was lower than previously reported as specialized care during pregnancy and delivery was available. However, maternal and fetal mortality remains prohibitively high in women with iPAH, although this conclusion is restricted by limited numbers. Early advice on contraception, pregnancy risk and fetal outcome remains paramount. PMID- 27384462 TI - Local extracellular matrix alignment directs cellular protrusion dynamics and migration through Rac1 and FAK. AB - Cell migration within 3D interstitial microenvironments is sensitive to extracellular matrix (ECM) properties, but the mechanisms that regulate migration guidance by 3D matrix features remain unclear. To examine the mechanisms underlying the cell migration response to aligned ECM, which is prevalent at the tumor-stroma interface, we utilized time-lapse microscopy to compare the behavior of MDA-MB-231 breast adenocarcinoma cells within randomly organized and well aligned 3D collagen ECM. We developed a novel experimental system in which cellular morphodynamics during initial 3D cell spreading served as a reductionist model for the complex process of matrix-directed 3D cell migration. Using this approach, we found that ECM alignment induced spatial anisotropy of cells' matrix probing by promoting protrusion frequency, persistence, and lengthening along the alignment axis and suppressing protrusion dynamics orthogonal to alignment. Preference for on-axis behaviors was dependent upon FAK and Rac1 signaling and translated across length and time scales such that cells within aligned ECM exhibited accelerated elongation, front-rear polarization, and migration relative to cells in random ECM. Together, these findings indicate that adhesive and protrusive signaling allow cells to respond to coordinated physical cues in the ECM, promoting migration efficiency and cell migration guidance by 3D matrix structure. PMID- 27384463 TI - Magnetization transfer imaging of cortical bone in vivo using a zero echo time sequence in mice at 4.7 T: a feasibility study. AB - OBJECTIVE: To investigate the feasibility of magnetization transfer (MT) imaging in mice in vivo for the assessment of cortical bone. MATERIALS AND METHODS: MT zero echo time data were acquired at 4.7 T in six mice using MT preparation pulses with two different flip angles (FAs) and a series of ten different off resonance frequencies (500-15000 Hz). Regions of interest were drawn at multiple levels of the femoral cortical bone. The MT ratio (MTR) was computed for each combination of FAs and off-resonance frequencies. T1 measurements were used to estimate the direct saturation (DS) using a Bloch equation simulation. Estimation of the absorption line width of cortical bone from T2* measurements was also performed. RESULTS: MTR values were higher using 3000 degrees FA than 1000 degrees FA. MTR values decreased toward higher off-resonance frequencies. Maximum mean MTR +/- standard deviation (SD) of 58.57 +/- 5.22 (range 50.44 70.61) was measured with a preparation pulse of 3000 degrees and off-resonance frequency of 500 Hz. Maximum "true" MT effect was estimated at around 2-3 and 5 kHz, respectively, for 1000 degrees and 3000 degrees FA. Mean full width at half maximum +/- SD of 577 +/- 91 Hz was calculated for the absorption spectral line of the cortical bone. CONCLUSION: MT imaging can be used for the assessment of cortical bone in mice in vivo. DS effects are negligible using preparation pulses with off-resonance frequencies greater than 3 kHz. PMID- 27384464 TI - Planktonic marine iron oxidizers drive iron mineralization under low-oxygen conditions. AB - Observations of modern microbes have led to several hypotheses on how microbes precipitated the extensive iron formations in the geologic record, but we have yet to resolve the exact microbial contributions. An initial hypothesis was that cyanobacteria produced oxygen which oxidized iron abiotically; however, in modern environments such as microbial mats, where Fe(II) and O2 coexist, we commonly find microaerophilic chemolithotrophic iron-oxidizing bacteria producing Fe(III) oxyhydroxides. This suggests that such iron oxidizers could have inhabited niches in ancient coastal oceans where Fe(II) and O2 coexisted, and therefore contributed to banded iron formations (BIFs) and other ferruginous deposits. However, there is currently little evidence for planktonic marine iron oxidizers in modern analogs. Here, we demonstrate successful cultivation of planktonic microaerophilic iron-oxidizing Zetaproteobacteria from the Chesapeake Bay during seasonal stratification. Iron oxidizers were associated with low oxygen concentrations and active iron redox cycling in the oxic-anoxic transition zone (<3 MUm O2 , <0.2 MUm H2 S). While cyanobacteria were also detected in this transition zone, oxygen concentrations were too low to support significant rates of abiotic iron oxidation. Cyanobacteria may be providing oxygen for microaerophilic iron oxidation through a symbiotic relationship; at high Fe(II) levels, cyanobacteria would gain protection against Fe(II) toxicity. A Zetaproteobacteria isolate from this site oxidized iron at rates sufficient to account for deposition of geologic iron formations. In sum, our results suggest that once oxygenic photosynthesis evolved, microaerophilic chemolithotrophic iron oxidizers were likely important drivers of iron mineralization in ancient oceans. PMID- 27384465 TI - Social networking in nursing education: integrative literature review. AB - OBJECTIVE: to identify the use of social networking in nursing education. METHOD: integrative literature review in the databases: LILACS, IBECS, Cochrane, BDENF, SciELO, CINAHL, Scopus, PubMed, CAPES Periodicals Portal and Web of Science, using the descriptors: social networking and nursing education and the keywords: social networking sites and nursing education, carried out in April 2015. RESULTS: of the 489 articles found, only 14 met the inclusion and exclusion criteria. Most studies were published after 2013 (57%), originating from the United States and United Kingdom (77.8%). It was observed the use of social networking among nursing students, postgraduate students, mentors and nurses, in undergraduate programmes, hybrid education (blended-learning) and in interprofessional education. The social networking sites used in the teaching and learning process were Facebook (42.8%), Ning (28.5%), Twitter (21.4%) and MySpace (7.1%), by means of audios, videos, quizzes, animations, forums, guidance, support, discussions and research group. CONCLUSION: few experiences of the use of social networking in nursing education were found and their contributions show the numerous benefits and difficulties faced, providing resourses for the improvement and revaluation of their use in the teaching and learning process. PMID- 27384466 TI - Predictive factors for the Nursing Diagnoses in people living with Acquired Immune Deficiency Syndrome. AB - OBJECTIVE: to identify the predictive factors for the nursing diagnoses in people living with Acquired Immune Deficiency Syndrome. METHOD: a cross-sectional study, undertaken with 113 people living with AIDS. The data were collected using an interview script and physical examination. Logistic regression was used for the data analysis, considering a level of significance of 10%. RESULTS: the predictive factors identified were: for the nursing diagnosis of knowledge deficit-inadequate following of instructions and verbalization of the problem; for the nursing diagnosis of failure to adhere - years of study, behavior indicative of failure to adhere, participation in the treatment and forgetfulness; for the nursing diagnosis of sexual dysfunction - family income, reduced frequency of sexual practice, perceived deficit in sexual desire, perceived limitations imposed by the disease and altered body function. CONCLUSION: the predictive factors for these nursing diagnoses involved sociodemographic and clinical characteristics, defining characteristics, and related factors, which must be taken into consideration during the assistance provided by the nurse. PMID- 27384467 TI - Assessment of a prototype for the Systemization of Nursing Care on a mobile device. AB - OBJECTIVES: assess a prototype for use on mobile devices that permits registering data for the Systemization of Nursing Care at a Neonatal Intensive Care Unit. METHOD: an exploratory and descriptive study was undertaken, characterized as an applied methodological research, developed at a teaching hospital. RESULTS: the mobile technology the nurses at the Neonatal Intensive Care Unit use was positive, although some reported they faced difficulties to manage it, while others with experience in using mobile devices did not face problems to use it. The application has the functions needed for the Systematization of Nursing Care at the unit, but changes were suggested in the interface of the screens, some data collection terms and parameters the application offers. The main contributions of the software were: agility in the development and documentation of the systemization, freedom to move, standardization of infant assessment, optimization of time to develop bureaucratic activities, possibilities to recover information and reduction of physical space the registers occupy. CONCLUSION: prototype software for the Systemization of Nursing Care with mobile technology permits flexibility for the nurses to register their activities, as the data can be collected at the bedside. PMID- 27384468 TI - What is the perception of biological risk by undergraduate nursing students? AB - OBJECTIVE: to analyze undergraduate nursing students' perception of biological risk and its relationship with their prior practical training. METHOD: a descriptive cross-sectional study was conducted among undergraduate nursing students enrolled in clinical practice courses in the academic year 2013-2014 at the School of Nursing at the University of Barcelona. VARIABLES: sociodemographic variables, employment, training, clinical experience and other variables related to the assessment of perceived biological risk were collected. Both a newly developed tool and the Dimensional Assessment of Risk Perception at the worker level scale (Escala de Evaluacion Dimensional del Riesgo Percibido por el Trabajador, EDRP-T) were used. STATISTICAL ANALYSIS: descriptive and univariate analysis were used to identify differences between the perception of biological risk of the EDRP-T scale items and sociodemographic variables. RESULTS: students without prior practical training had weaker perceptions of biological risk compared to students with prior practical training (p=0.05 and p=0.04, respectively). Weaker perceptions of biological risk were found among students with prior work experience. CONCLUSION: practical training and work experience influence the perception of biological risk among nursing students. PMID- 27384469 TI - The experience of nurses in care for culturally diverse families: A qualitative meta-synthesis. AB - OBJECTIVE: to understand the experience of nurses in care delivery to culturally diverse families. METHOD: qualitative meta-synthesis. Exhaustive search in seven databases, three repositories and a manual search in references without time limit, in English, Spanish and Portuguese, resulting in 1609 potentially relevant studies. These were assessed based on the title, summary and full text, determining the final inclusion of 14 studies. Two independent reviewers used the Critical Appraisal Skills Programme (CASP) to assess the quality. The interpretative synthesis implied permanent contrast and consensus among the authors, revealing four categories and one meta-theme. RESULTS: "taking care of a culturally diverse family, the experience of crossing a tightrope". CONCLUSION: the experience of nurses in care delivery to culturally diverse families is demanding and challenging because it imprints a constant tension among barriers, cultural manifestations and the ethical responsibility of care, incipiently revealing elements of cultural competency. The omission of information in the participants' reports in the studies represents a limitation. The findings offer a baseline for professionals and organizations to focus their intervention efforts on the continuing barriers in care delivery to culturally diverse families and strengthens the need for cultural competency training for nurses. PMID- 27384470 TI - Systematic Review of the profile of emergency contraception users. AB - Abastract Objective: to discern the profile of the Spanish Emergency Contraceptive users (EC). DESIGN: systematic review of contraceptive use in the Spanish population. DATA SOURCE: Spanish and international databases, between January 2006 - March 2011. KEYWORDS: Contraceptives, Postcoital pills, emergency contraception, levonorgestrel, data collection. STUDY SELECTION: original papers, letters to the editor in which stated aims were the description, prediction or measurement of variables related to EC use. Twenty-two papers were retrieved and fourteen were finally selected, all of which were descriptive. DATA EXTRACTION: manuscripts were evaluated by two independent reviewers. RESULTS: Women requesting EC have ages between 21-24 years, mostly single and university students; declare that they have not previously used EC, and attend an Emergency department, at weekends and within 48 hours following unprotected sexual intercourse. The reason is condom rupture. None of the studies reviewed measured alcohol and other drug consumption, the number of sexual partners, nor any of the studies performed a comparison with a group not using EC. CONCLUSIONS: lack of homogeneity and comprehensiveness of studied variables resulted in a limited profile of Spanish EC users. Further studies are needed with a more comprehensive approach if sexual health interventions are to be carried out in possible users. PMID- 27384472 TI - Selective dual-purpose photocatalysis for simultaneous H2 evolution and mineralization of organic compounds enabled by a Cr2O3 barrier layer coated on Rh/SrTiO3. AB - Dual-functional photocatalysis for H2 evolution with the simultaneous mineralization of 4-chlorophenol was achieved under de-aerated conditions using a Cr2O3/Rh/SrTiO3 photocatalyst which has Rh nanoparticles covered with a thin Cr2O3 barrier layer to selectively control and maximize the dual-functional photocatalytic activity. PMID- 27384471 TI - Implications of respiratory motion for small animal image-guided radiotherapy. AB - Image-guided small animal irradiators have the potential to make a significant impact on facilitating the translation of radiobiological research into the clinic. To fully exploit the improved precision in dose delivery to the target/tumour while minimizing dose to surrounding tissues, minimal positional error in the target is required. However, for many sites within the thorax and abdomen, respiratory motion may be a critical factor in limiting the accuracy of beam delivery and until now, very little attention has been paid to the impact and management of this motion. We report on the implications of respiratory motion with respect to the negative impact of delivered dose distributions and their assessment, ways being developed to effectively manage this motion, so that beam delivery only occurs during the stationary resting phase of the breathing cycle, and comment on the need to effectively integrate these developments into the software used to plan and control beam delivery. Altogether, the implementation of respiratory-gated imaging and beam delivery will lead to significant improvements in the precision in dose delivery and constitutes an important development for preclinical radiotherapy studies. PMID- 27384473 TI - Local coexistence of VO2 phases revealed by deep data analysis. AB - We report a synergistic approach of micro-Raman spectroscopic mapping and deep data analysis to study the distribution of crystallographic phases and ferroelastic domains in a defected Al-doped VO2 microcrystal. Bayesian linear unmixing revealed an uneven distribution of the T phase, which is stabilized by the surface defects and uneven local doping that went undetectable by other classical analysis techniques such as PCA and SIMPLISMA. This work demonstrates the impact of information recovery via statistical analysis and full mapping in spectroscopic studies of vanadium dioxide systems, which is commonly substituted by averaging or single point-probing approaches, both of which suffer from information misinterpretation due to low resolving power. PMID- 27384474 TI - PCP4/PEP19 promotes migration, invasion and adhesion in human breast cancer MCF-7 and T47D cells. AB - Purkinje cell protein (PCP) 4/peptide (PEP) 19 is expressed in Purkinje cells where it has a calmodulin-binding, anti-apoptotic function. We recently demonstrated that PCP4/PEP19 is expressed and inhibit apoptosis in human breast cancer cell lines. In the present study we investigated the role of PCP4/PEP19 in cell morphology, adhesion, migration, and invasion in MCF-7 and T47D human breast cancer cell lines. Knockdown of PCP4/PEP19 reduced the formation of filopodia like cytoplasmic structures and vinculin expression, and enhanced E-cadherin expression. Activities of migration, invasion, and cell adhesion were also decreased after the knockdown of PCP4/PEP19 in MCF-7 and T47D cells. These results suggested that PCP4/PEP19 promotes cancer cell adhesion, migration, and invasion and that PCP4/PEP19 may be a potential target for therapeutic agents in breast cancer treatment which act by inhibiting epithelial-mesenchymal transition and enhancing apoptotic cell death. PMID- 27384475 TI - Thyroid hormone synthesis: a potential target of a Chinese herbal formula Haizao Yuhu Decoction acting on iodine-deficient goiter. AB - Haizao Yuhu Decoction (HYD), a famous multi-component herbal formula, has been widely used to treat various thyroid-related diseases, including iodine-deficient goiter. Herb pair Thallus Sargassi Pallidi (HZ) and Radix Glycyrrhizae (GC), one of the so-called "eighteen antagonistic medicaments", contains in HYD. To explore pharmacological mechanisms of HYD acting on iodine-deficient goiter and to provide evidence for potential roles of herb pair HZ and GC in HYD, our genome wide microarray detection and network analysis identified a list of goiter related genes, mainly involved into the alterations in hypothalamus-pituitary thyroid/gonad/growth axes. Then, the disease genes-drug genes interaction network illustrated the links between HYD regulating genes and goiter-related genes, and identified the candidate targets of HYD acting on goiter. Functionally, these candidate targets were closely correlated with thyroid hormone synthesis. Moreover, the potential regulating genes of herb pair HZ and GC were revealed to be crucial components in the pathway of thyroid hormone synthesis. The prediction results were all verified by following experiments based on goiter rats. Collectively, this integrative study combining microarray gene expression profiling, network analysis and experimental validations offers the convincing evidence that HYD may alleviate iodine-deficient goiter via regulating thyroid hormone synthesis, and explains the necessity of herb pair HZ and GC in HYD. Our work provides a novel and powerful means to clarify the mechanisms of action for multi-component drugs such as herbal formulae in a holistic way, which may improve drug development and applications. PMID- 27384476 TI - Mitotic p21Cip1/CDKN1A is regulated by cyclin-dependent kinase 1 phosphorylation. AB - The multifunctional protein p21Cip1/CDKN1A (p21) is an important and universal Cdk-interacting protein. Recently, we have reported that p21 is involved in the regulation of the mitotic kinase Cdk1/cyclin B1 and critical for successful mitosis and cytokinesis. In the present work we show that S130 of p21 is phosphorylated by Cdk1/cyclin B1 during mitosis, which reduces p21's stability and binding affinity to Cdk1/cyclin B1. Interfering with this phosphorylation results in extended mitotic duration and defective chromosome segregation, indicating that this regulation ensures proper mitotic progression. Given that p53, the major transcriptional activator of p21, is the most frequently mutated gene in human cancer and that deregulated Cdk1 associates with the development of different types of cancer, this work provides new insight into the understanding of how deregulated p21 contributes to chromosomal instability and oncogenesis. PMID- 27384477 TI - Androgen receptor as potential therapeutic target in metastatic endometrial cancer. AB - PURPOSE: The expression and involvement of estrogen (ER) and progesterone receptor (PR) is extensively studied in endometrial cancer. Androgen receptor (AR) is a hormone receptor less studied in female cancers, and we here aim to investigate the expression level of AR in endometrial cancer precursor lesions, primary tumors and metastases, and its potential as therapeutic target. RESULTS: Expression of AR was observed in 93% of hyperplasias, but only in 41% of non endometrioid tumors. Compared to estrogen and progesterone receptor AR is more commonly expressed in metastatic lesions, and AR status is discordant in primary and metastatic lesions in a large proportion of cases. AR protein level was significantly associated with survival (P < 0.001), and a calculated AR to ERalpha ratio identified a subgroup of patients with particular poor outcome. The anti-androgen enzalutamide may have a growth inhibitory effect in endometrial cancer cells based on experiments with primary endometrial tumor cells. MATERIALS AND METHODS: 718 primary endometrial cancers and 298 metastatic lesions (from 142 patients) were investigated for expression of AR in relation to survival, clinical and histopathological data. Protein levels were investigated by immunohistochemistry and reverse phase protein array; mRNA levels by DNA oligonucleotide microarray. The effect of androgen stimulation and inhibition was tested on primary endometrial tumor cells. CONCLUSIONS: A large proportion of metastatic endometrial cancer lesions express AR, which may be a potential target in these patients. Treatment targeting AR may be of particular benefit in patients with high AR levels compared to ERalpha levels. PMID- 27384478 TI - The contribution of serum hepatitis B virus load in the carcinogenesis and prognosis of hepatocellular carcinoma: evidence from two meta-analyses. AB - BACKGROUND AND AIM: The meta-analysis aimed to quantify and summarize the contribution of serum hepatitis B virus (HBV) DNA load in the carcinogenesis and prognosis of hepatocellular carcinoma (HCC). RESULTS: Nine independent studies with a total of 1162 cases and 9365 participants on risk of HCC and seventeen studies with 1342 cases and 2891 participants on recurrence of HCC were finally included. The non-liner dose-response association between HBV DNA level and HCC risk was observed, with P value equal to 0.02 for linear test. Compared with 2 log10copies/ml HBV DNA level carriers, the summary relative risk of HCC were 1.65(95% CI: 0.94-2.92) for 4.5 log10copies/ml, 2.20(95% CI: 1.00-4.85) for 5.5 log10copies/ml, 3.06(95% CI: 1.11-8.44) for 6.5 log10copies/ml. Moreover, individuals with high viral load (HBV DNA levels > 105copies/ml) presented significant association with increased risk of HCC recurrence, with the pooled RR of 1.69 (95% CI: 1.49-1.92). MATERIALS AND METHODS: Pertinent studies were identified by searching PubMed, Embase and ISI Web of science databases up to January 2016 and by reviewing the references of retrieved articles. The dose response meta-analysis was precisely performed to calculate the summary relative risks (RRs) by quantizing the association between HBV load and risk of HCC. Besides, the contribution of HBV load on recurrence of HCC was further clarified by general meta-analysis. CONCLUSIONS: These findings indicated a non-linear dose response relationship between serum HBV DNA level and risk of HCC, and confirmed the significant contribution of serum HBV DNA level in the prognosis of HCC. PMID- 27384479 TI - Desferal regulates hCtr1 and transferrin receptor expression through Sp1 and exhibits synergistic cytotoxicity with platinum drugs in oxaliplatin-resistant human cervical cancer cells in vitro and in vivo. AB - The development of resistance to platinum drugs in cancer cells severely reduces the efficacy of these drugs. Thus, the discovery of novel drugs or combined strategies to overcome drug resistance is imperative. In addition to our previous finding that combined D-penicillamine with platinum drugs exerts synergistic cytotoxicity, we recently identified a novel therapeutic strategy by combining an iron chelating agent desferal with platinum drugs to overcome platinum resistance in an oxaliplatin-resistant human cervical cancer cell line, S3. Further study demonstrated that the level of platinum-DNA adduct formation positively correlated with cell death in combination of desferal with platinums than that of each drug alone in S3 cells. Decrement of human copper transporter 1 (hCtr1) and transferrin receptor 1 (TfR1) expression involved in the development of platinum resistance in S3 cells. Moreover, desferal promoted the expression of hCtr1 through the upregulation of Sp1. The overexpression of Sp1 increased the expression of NF-kappaB and translocated it into the nucleus to bind to the TfR1 promoter region, which subsequently increased the expression of TfR1. Importantly, the cotreatment of oxaliplatin with desferal significantly potentiated the oxaliplatin-elicited antitumoral effect in the oxaliplatin resistant xenograft animal model without any toxic effect observed. Taken together, these results demonstrated that the combination of desferal with oxaliplatin can overcome oxaliplatin resistance through the regulation of hCtr1 and TfR1, and may have beneficial effect for treatment of patient with oxaliplatin-refractory tumors. PMID- 27384480 TI - The emergence of T790M mutation in EGFR-mutant lung adenocarcinoma patients having a history of acquired resistance to EGFR-TKI: focus on rebiopsy timing and long-term existence of T790M. AB - Different growth kinetics occurring between the sensitive and T790M-containing cells may result in the repopulation of tumor cells over time. Little information has yet been uncovered on whether rebiopsy timing influences the T790M detection rate. We enrolled a total of 98 epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients, who had a history of acquired resistance to EGFR tyrosine kinase inhibitor (TKI) and available rebiopsy tumor specimens for reassessment of EGFR mutations. Rebiopsy was performed at the time of first EGFR TKI progression in 54 patients (55.1%); for the other 44 patients (44.9%), rebiopsy was done with an interval from first EGFR-TKI progression (median 470.5 days, range 46-1742 days). Our results indicated that rebiopsy timing did not influence the detection rate of T790M and that the mutation could be identified in patients with a long EGFR-TKI-free interval. For patients without suitable lesions for rebiopsy at the time of EGFR-TKI progression, an attempt to rebiopsy should be considered during the subsequent treatment courses. PMID- 27384481 TI - Aldehyde dehydrogenase inhibition combined with phenformin treatment reversed NSCLC through ATP depletion. AB - Among ALDH isoforms, ALDH1L1 in the folate pathway showed highly increased expression in non-small-cell lung cancer cells (NSCLC). Based on the basic mechanism of ALDH converting aldehyde to carboxylic acid with by-product NADH, we suggested that ALDH1L1 may contribute to ATP production using NADH through oxidative phosphorylation. ALDH1L1 knockdown reduced ATP production by up to 60% concomitantly with decrease of NADH in NSCLC. ALDH inhibitor, gossypol, also reduced ATP production in a dose dependent manner together with decrease of NADH level in NSCLC. A combination treatment of gossypol with phenformin, mitochondrial complex I inhibitor, synergized ATP depletion, which efficiently induced cell death. Pre-clinical xenograft model using human NSCLC demonstrated a remarkable therapeutic response to the combined treatment of gossypol and phenformin. PMID- 27384482 TI - Sohlh2 suppresses epithelial to mesenchymal transition in breast cancer via downregulation of IL-8. AB - Breast cancer is one of the deadliest cancers worldwide due to its strong metastasis to other organs. Metastasis of breast cancer involves a complex set of events, including epithelial-mesenchymal transition (EMT) that increases invasiveness of the tumor cells. We previously identified sohlh2 is a tumor suppressor in the pathogenesis of ovarian cancer. However, the functions of sohlh2 in breast cancer cell migration and invasion remain unknown. Here we report a novel sohlh2/IL-8 signaling pathway in the invasive breast cancer. We observed sohlh2 expression was downregulated in the metastatic breast cancer. Ectopic sohlh2 expression in breast cancer cells reduced EMT and inhibited cell migration and invasion in vitro, and metastasis in vivo. Moreover, the depletion of sohlh2 induced the opposite effects to ectopic sohlh2 expression. RNA-Seq data from a sohlh2 knockdown breast cancer cell line showed that after sohlh2 depletion, the mRNA level of interleukin 8 (IL-8) was significantly increased in these cancer cells, which consequently increased secretion of IL-8 protein. Using chromatin immunoprecipitation and reporter assays, we demonstrated that sohlh2 bound to IL-8 promoter and repressed its activities. The enhanced migration and invasion in sohlh2 -ablated MCF-7 cells were blocked by knockdown of IL-8 expression, while exogenous IL-8 neutralized the anti-migratory and invasive activities of sohlh2 in MDA-MB-231cells. Overall, these results demonstrate that sohlh2 functions as a tumor metastasis suppressor via suppressing IL-8 expression in breast cancer. PMID- 27384483 TI - beta-catenin signaling is required for RAS-driven thyroid cancer through PI3K activation. AB - Mutations in beta-catenin are traditionally described as late events in thyroid cancer progression. However, the functional implications of beta-catenin dysregulation in the context of tumor initiating events remain unclear. The aim of this work was to investigate whether the two main oncogenic drivers in thyroid cancer, RAS and BRAF, could activate the Wnt/beta-catenin pathway. Expression of HRASV12 but not BRAFV600E in thyroid cells induced beta-catenin nuclear localization, increased beta-catenin-dependent transcriptional activity and inhibited GSK3beta. In a panel of human thyroid cancer cell lines representative of the main genetic events in thyroid cancer, beta-catenin activation was highly dependent on PI3K/AKT activity through its phosphorylation at S552, but not on MAPK. Silencing of beta-catenin expression in cell lines led to a dramatic reduction in proliferation due to an induction of senescence, which was concordant with a reduction in tumor size in nude mice. Moreover, beta-catenin silencing suppressed the expression of EMT-related genes and reduced the invasive capacity of the tumor cells. In conclusion, this work demonstrates that RAS driven tumors induce PI3K/AKT-dependent beta-catenin activation. PMID- 27384484 TI - High expression of MnSOD promotes survival of circulating breast cancer cells and increases their resistance to doxorubicin. AB - Understanding the survival mechanism of metastatic cancer cells in circulation will provide new perspectives on metastasis prevention and also shed new light on metastasis-derived drug resistance. In this study, we made it feasible to detect apoptosis of circulating tumor cells (CTCs) in real-time by integrating a fluorescence resonance energy transfer (FRET)-based caspase sensor into one in vitro microfluidic circulatory system, and two in vivo models: zebrafish circulation and mouse lung metastatic model. Our study demonstrated that fluid shear stresses triggered apoptosis of breast cancer cells in circulation by elevating the mitochondrial production of the primary free radical, superoxide anion. Cancer cells with high levels of manganese superoxide dismutase (MnSOD) exhibited stronger resistance to shear force-induced apoptosis and formed more lung metastases in mice. These metastasized cells further displayed higher resistance to chemotherapeutic agent doxorubicin, which also generates superoxide in mitochondria. Specific siRNA-mediated MnSOD knockdown reversed all three phenotypes. Our findings therefore suggest that MnSOD plays an important integrative role in supporting cancer cell survival in circulation, metastasis, and doxorubicin resistance. MnSOD can serve as a new biomarker for identifying metastatic CTCs and a novel therapeutic target for inhibiting metastasis and destroying doxorubicin-resistant breast cancer cells. PMID- 27384485 TI - Inhibition of ERalpha/ERK/P62 cascades induces "autophagic switch" in the estrogen receptor-positive breast cancer cells exposed to gemcitabine. AB - Several clinical trials revealed that estrogen receptor (ER) status had relevance to the response of mammary malignancy to chemotherapy. Autophagy has emerged as an important cellular mechanism of tumor cells in response to anticancer therapy. The aim of this study is to investigate whether gemcitabine induces autophagy, and more importantly, whether such autophagy is functional relevant to the therapeutic effects of gemcitabine in breast cancer cells in relation to the ER status. In our study, autophagy was induced both in ER+ MCF-7 and ER- MDA-MB-231 cells by gemcitabine markedly, while the autophagy plays distinct roles - cytoprotective in ER- MDA-MB-231 and cytotoxic in ER+ MCF-7 cells. Gemcitabine treatment leads to the activation of ERalpha-ERK-P62 signal pathway in MCF-7 cells which may augment the autophagic degradation, thus results in the excessive activation of autophagy and irreversible autophagic cell death eventually. Inhibition of ERalpha-ERK-P62 cascades in MCF-7 cells by small interfering RNA or PD98059 impairs the autophagic degradation, and leads to "autophagic switch" - from cytotoxic autophagy to cytoprotection. Moreover, stable overexpression of ERalpha in the ER- BCap37 breast cancer cell line enhances the gemcitabine induced autophagy flux and switches the autophagic cytoprotection in ER- BCap37 to cytotoxicity effect in ER+ BCap37 cells. Our study firstly demonstrated that ER status influences gemcitabine efficacy via modulating the autophagy in breast cancer cells. PMID- 27384487 TI - CALR mutation characterization in myeloproliferative neoplasms. AB - Identification of somatic frameshift mutations in exon 9 of the calreticulin gene (CALR) in myeloproliferative neoplasms (MPNs) in December of 2013 has been a remarkable finding. It has provided a new molecular diagnostic marker, particularly in essential thrombocythemia (ET) and primary myelofibrosis (PMF), where is the second most common altered gene after JAK2V617F. There are two main types of CALR mutants, type 1 and type 2, and there is evidence about their distinct clinical/prognostic implications, for instances, it is believed that favorable outcome might be restricted to type-1 in PMF. By using reasoned approaches, very recent publications have supported classifying the alternative mutants in type-1-like or type-2-like. If further studies confirm these results, new considerations may be taken into account in the molecular diagnosis of MPNs. This implies that precise mutation characterization must be performed and caution should be taken in screening technique selection. In this Editorial we summarize the current information regarding all this issues. PMID- 27384486 TI - Enhanced cytotoxicity of reovirus and radiotherapy in melanoma cells is mediated through increased viral replication and mitochondrial apoptotic signalling. AB - Oncolytic viruses selectively target and replicate in cancer cells, providing us with a unique tool with which to target and kill tumour cells. These viruses come from a diverse range of viral families including reovirus type 3 Dearing (RT3D), a non-pathogenic human double-stranded RNA oncolytic virus, which has been shown to be an effective therapeutic agent, both as a mono-therapy and in combination with traditional chemotherapeutic drugs. This study investigated the interaction between RT3D and radiotherapy in melanoma cell lines with a BRAF mutant, Ras mutant or BRAF/Ras wild type genotype. The data indicates that RT3D combined with radiotherapy significantly increased cytotoxicity relative to either single agent, independent of genotype, both in vitro and in vivo. The mechanism of enhanced cytotoxicity was dependent on an increase in viral replication, mediated by CUG2 up-regulation and subsequent down-regulation of pPKR and p-eIF2alpha, leading to the activation of mitochondrial apoptotic signalling resulting in increased cell death. PMID- 27384489 TI - Relationship between LRRK2 R1628P polymorphism and Parkinson's disease in Asian populations. AB - Although the leucine-rich repeat kinase 2 (LRRK2) R1628P polymorphism has been associated with the risk of Parkinson's disease (PD) in Taiwan, China, and Singapore, there are conflicting findings regarding this relationship. Thus, the aim of the present meta-analysis was to evaluate the associations between the LRRK2 R1628P polymorphism (rs33949390) and PD in Asian populations. A search for eligible studies was performed in PubMed, Embase, SinoMed, and the China Knowledge Resource Integrated Database, and pooled odds ratios and 95% confidence intervals were used to evaluate the strength of the association between the R1628P polymorphism and PD. This meta-analysis assessed 19 studies from 14 papers that involved a total of 9,927 PD patients and 8,602 controls and found that the R1628P polymorphism was significantly associated with the risk of PD in Asian populations. Moreover, stratification analyses indicated that the R1628P polymorphism was significantly associated with an increased risk of PD among Chinese as well as non-Chinese Asian populations and an increased risk of PD in Chinese patients from China, Taiwan, and Singapore. In a stratified analysis conducted according to age, significant associations were found for both late onset PD and early-onset PD. The present data indicate that the R1628P polymorphism of the LRRK2 gene contributes to PD susceptibility in Asian, especially Chinese, populations. PMID- 27384488 TI - EPCs enhance angiogenesis in renal regeneration. AB - Decellularized renal scaffolds have previously been used for renal regeneration following partial nephrectomy, in which angiogenesis played a key role. In this study, rats underwent partial nephrectomy and repaired with decellularized renal scaffolds. Subsequently, the labeled EPCs were intravenously injected into rats in EPCs group, and the control group received an equal amount of phosphate-buffer saline (PBS). We chose 1, 2 and 4 weeks post operation as time point. Average microvascular density (aMVD) analyses revealed higher angiogenesis in EPCs group compared with the control group. The expression of angiogenic growth factors including vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) and hypoxia-inducible factors 1-alpha (HIF-1alpha), was generally higher in the EPCs group in all weeks (1, 2 and 4), and peaked in week 2. EPCs were observed to home into renal injury site, promoting angiogenesis across the renal parenchyma-scaffold interface to be potentially used as bridges for EPCs to migrate into the implanted scaffolds. Administration of exogenous EPCs promotes angiogenesis and vasculogenesis in decellularized renal scaffolds-mediated renal regeneration, providing adequate microenvironment for kidney recovery post renal injury. PMID- 27384490 TI - Circulating nano-particulate TLR9 agonist scouts out tumor microenvironment to release immunogenic dead tumor cells. AB - Recent evidence suggest that a beta-glucan derived from mushroom Schizophyllan(SPG) complexed with a humanized TLR9 agonistic CpG DNA, K3 (K3-SPG) is a promising vaccine adjuvant that induces robust CD8 T cell responses to co administered antigen. However, it has not been investigated whether K3-SPG alone can act as an anti-cancer immunotherapeutic agent or not. Here, we demonstrate that intravenous injection of K3-SPG, but not CpG alone, is accumulated in the tumor microenvironment and triggered immunogenic cell death (ICD) of tumor cells by local induction of type-I interferon (IFN) as well as IL-12. Resultant innate immune activation as well as subsequent tumor-specific CD8 T cell responses were contributed the tumor growth suppression. This anti-tumor effect of K3-SPG monotherapy was also confirmed by using various tumor models including pancreatic cancer peritoneal dissemination model. Taken together, nano-particulate TLR9 agonist injected intravenously can scout out tumor microenvironment to provoke local innate immune activation and release dead tumor cells into circulation that may induce broader and protective tumor antigen-specific CD8 T cells. PMID- 27384492 TI - Rapamycin in aging and disease: maximizing efficacy while minimizing side effects. AB - Experimental geroscience has identified rapamycin as a top candidate for promoting healthy aging and longevity in mammals. As multiple independent studies have successfully reproduced the lifespan and healthspan promoting effects of rapamycin, the focus has shifted to possible translational use. While a promising compound, clinical use of rapamycin is limited by concerns of side effects associated with the drug. Studies aimed at defining optimal dosage regimen, delivery route, and formulation will allow for benefits to be maximized while reducing side effects. PMID- 27384493 TI - Study on the Influence of Tea Extract on Probiotics in Skim Milk: From Probiotics Propagation to Metabolite. AB - In this study, the influence of tea extract (TE) on the growth of probiotics in skim milk was examined. Lactobacillus plantarum ST-III, Bifidobacterium bifidum Bb02, Lactobacillus acidophilus NCFM, and Lactobacillus rhamnosus GG were used in this study. The introduction of TE in milk significantly stimulated the propagation and acidification of L. rhamnosus GG and L. acidophilus NCFM. The antioxidant capacities and the total free amino acid contents of all fermented milk products were enhanced by the addition of TE; however, there were different antioxidant properties and free amino acid contents of fermented milk samples fermented by different bacteria. With a 9% (w/w) level, the fermentation with L. rhamnosus GG and L. acidophilus NCFM showed larger numbers of viable cells and faster acidifying rates, as well as excellent antioxidant capacity and abundant free amino acids. The stimulative effects of TE on probiotics can be considered for industrial purposes and has practical implications for commercial applications. PMID- 27384491 TI - The mitochondrial-derived peptide humanin activates the ERK1/2, AKT, and STAT3 signaling pathways and has age-dependent signaling differences in the hippocampus. AB - Humanin is a small secreted peptide that is encoded in the mitochondrial genome. Humanin and its analogues have a protective role in multiple age-related diseases including type 2 diabetes and Alzheimer's disease, through cytoprotective and neuroprotective effects both in vitro and in vivo. However, the humanin-mediated signaling pathways are not well understood. In this paper, we demonstrate that humanin acts through the GP130/IL6ST receptor complex to activate AKT, ERK1/2, and STAT3 signaling pathways. Humanin treatment increases phosphorylation in AKT, ERK 1/2, and STAT3 where PI3K, MEK, and JAK are involved in the activation of those three signaling pathways, respectively. Furthermore, old mice, but not young mice, injected with humanin showed an increase in phosphorylation in AKT and ERK1/2 in the hippocampus. These findings uncover a key signaling pathway of humanin that is important for humanin's function and also demonstrates an age specific in vivo effect in a region of the brain that is critical for memory formation in an age-dependent manner. PMID- 27384494 TI - Microcanonical and resource-theoretic derivations of the thermal state of a quantum system with noncommuting charges. AB - The grand canonical ensemble lies at the core of quantum and classical statistical mechanics. A small system thermalizes to this ensemble while exchanging heat and particles with a bath. A quantum system may exchange quantities represented by operators that fail to commute. Whether such a system thermalizes and what form the thermal state has are questions about truly quantum thermodynamics. Here we investigate this thermal state from three perspectives. First, we introduce an approximate microcanonical ensemble. If this ensemble characterizes the system-and-bath composite, tracing out the bath yields the system's thermal state. This state is expected to be the equilibrium point, we argue, of typical dynamics. Finally, we define a resource-theory model for thermodynamic exchanges of noncommuting observables. Complete passivity-the inability to extract work from equilibrium states-implies the thermal state's form, too. Our work opens new avenues into equilibrium in the presence of quantum noncommutation. PMID- 27384495 TI - Study with Analytical Equations of Absorption Spectra Containing Interference Dips in Fluoride Glasses Doped with Cr(3.). AB - The optical absorption of Cr(3+)-doped fluoride glasses has been investigated. The lowest energy absorption band (4)A2 -> (4)T2 shows distinct interference dips due to spin-orbit coupling between (4)T2, (2)E and (2)T1 excited states. The dips were analyzed using an analytical method proposed by Bussiere et al. ( J. Phys. Chem. A 2003 , 107 , 1258 ) based on coupled potential energy surfaces. Then a theoretical crystal-field analysis based on the Racah tensor algebraic method was carried on Cr(3+) ions occupying octahedral site symmetry in the fluoride glasses. Satisfactory correlations were obtained between the experimental and calculated energy levels. The fitting of the interference dips also provided a measure of the spin-orbit coupling constant for Cr(3+) in fluoride glasses, intermediate between the theoretical value calculated for a fluoride crystal and the value deduced from Racah parameters. PMID- 27384497 TI - Bipolar disorder: multiple pathways to neuroprogression. PMID- 27384496 TI - Psychosocial predictors and moderators of weight management programme outcomes in ethnically diverse obese youth. AB - BACKGROUND: An important area of research in childhood obesity is the identification of factors that predict or moderate the responses to obesity intervention programmes, yet few studies have examined the impact of self-esteem and family functioning on obesity treatment outcomes. OBJECTIVES: We sought to determine whether baseline self-esteem and family functioning predicted or moderated childhood obesity intervention outcomes at 6 months. METHODS: From 2009 to 2011, seventy-five 10-16 year old, racially/ethnically diverse obese youths with abnormal glucose tolerance were randomized to 6 months of an intensive family-based obesity lifestyle intervention (Bright Bodies) or routine outpatient Clinic Care. We examined youth self-concept, parent-rated family functioning and 6-month outcomes (youths' glucose tolerance, weight, body mass index and percent fat). We set the significance threshold as P <= 0.05 for moderator and predictor analyzes. RESULTS: Having poor family functioning and self-concept scores indicating high anxiety and low self-esteem at baseline predicted poor 6-month outcomes overall (Bright Bodies and Clinic Care groups combined). Additionally, baseline self-esteem and family functioning moderated treatment effects such that Bright Bodies outperformed Clinic Care in youths with low self-esteem and poorly functioning families, whereas youths with high self-esteem and high-functioning families did similarly well with either intervention. DISCUSSION: Our findings suggest intensive family-based lifestyle programmes are particularly beneficial for youth with low self-esteem and poorly functioning families. PMID- 27384498 TI - 454-Pyrosequencing analysis of highly adapted azo dye-degrading microbial communities in a two-stage anaerobic-aerobic bioreactor treating textile effluent. AB - Azo dyes, which are widely used in the textile industry, exhibit significant toxic characteristics for the environment and the human population. Sequential anaerobic-aerobic reactor systems are efficient for the degradation of dyes and the mineralization of intermediate compounds; however, little is known about the composition of the microbial communities responsible for dye degradation in these systems. 454-Pyrosequencing of the 16S rRNA gene was employed to assess the bacterial biodiversity and composition of a two-stage (anaerobic-aerobic) pilot scale reactor that treats effluent from a denim factory. The anaerobic reactor was inoculated with anaerobic sludge from a domestic sewage treatment plant. Due to the selective composition of the textile wastewater, after 210 days of operation, the anaerobic reactor was dominated by the single genus Clostridium, affiliated with the Firmicutes phylum. The aerobic biofilter harbored a diverse bacterial community. The most abundant phylum in the aerobic biofilter was Proteobacteria, which was primarily represented by the Gamma, Delta and Epsilon classes followed by Firmicutes and other phyla. Several bacterial genera were identified that most likely played an essential role in azo dye degradation in the investigated system. PMID- 27384499 TI - Referral decision support in patients with subacute brain injury: evaluation of the Rehabilitation Complexity Scale - Extended. AB - PURPOSE: To test if the Rehabilitation Complexity Scale Extended (RCS-E) can be used as decision support for patient referral to primary rehabilitation as either complex specialized services (CSS) or district specialist services (DSS). METHOD: Two independent expert teams analyzed medical records on 299 consecutive patients admitted for CSS or DSS rehabilitation. One team provided a golden standard for the patient referrals, and the other team provided RCS-E scores. Models for predicting referrals from RCS-E scores were developed on data for 149 patients and tested on the remaining 150 patients. RESULTS: The optimal RCS-E sum score threshold for referral prediction was 11, predicting the golden standard for patient referral with sensitivity 88%, specificity 78% and correct classification rate 81%. Improved referral prediction performance was achieved by using RCS-E item-wise score thresholds (sensitivity 81%, specificity 89%, correct classification rate 87%). The RCS-E sum score range for patients referred CSS and DSS by the item-wise model was, respectively, 0-12 and 2-22 suggesting strong non linear interaction of the RCS-E items. CONCLUSIONS: We found excellent referral decision support in the RCS-E and the item specific threshold model, when patients with acquired brain injury are to be referred to CSS or DSS as their primary rehabilitation. Implications for Rehabilitation Efficient rehabilitation after acquired brain injury requires rehabilitation settings that meet patient needs. Validated tools for referral decision support make the process more transparent. Patient rehabilitation complexity can be stratified by the RCS-E with high sensitivity, specificity and predictive value of positive test. RCS-E is an excellent tool for referral decision support. PMID- 27384501 TI - Mobile health: the power of wearables, sensors, and apps to transform clinical trials. AB - Mobile technology has become a ubiquitous part of everyday life, and the practical utility of mobile devices for improving human health is only now being realized. Wireless medical sensors, or mobile biosensors, are one such technology that is allowing the accumulation of real-time biometric data that may hold valuable clues for treating even some of the most devastating human diseases. From wearable gadgets to sophisticated implantable medical devices, the information retrieved from mobile technology has the potential to revolutionize how clinical research is conducted and how disease therapies are delivered in the coming years. Encompassing the fields of science and engineering, analytics, health care, business, and government, this report explores the promise that wearable biosensors, along with integrated mobile apps, hold for improving the quality of patient care and clinical outcomes. The discussion focuses on groundbreaking device innovation, data optimization and validation, commercial platform integration, clinical implementation and regulation, and the broad societal implications of using mobile health technologies. PMID- 27384500 TI - Differences between familial and sporadic early spondyloarthritis: results from the ESPERANZA cohort. AB - OBJECTIVES: To describe and evaluate clinical and imaging differences between patients with familial and sporadic early spondyloarthritis (SpA). METHODS: This was a cross-sectional study analysing the baseline dataset from ESPERANZA, a national programme developed for the early identification of patients with SpA. Patients fulfilling SpA ASAS classification criteria were included. Familial SpA was defined according to the ASAS/ESSG criteria as the presence in first- or second-degree relatives of any of the following: ankylosing spondylitis, psoriasis, uveitis, reactive arthritis, and inflammatory bowel disease. Socio demographic and disease characteristics, disease activity, metrology and laboratory and imaging data were compared by descriptive and bivariate statistics. RESULTS: A total of 377 patients were included - 64% men, mean age 32, and mean disease duration 12 months. Out of these, 132 (35%) patients (101 axial and 31 peripheral SpA) were familial forms. In patients with axial SpA, statistically significant differences (p<0.05) were found between familial and sporadic forms regarding age at symptoms onset (29.4+/-9.2 vs. 31.5+/-10 years), HLA B27 positivity (83% vs. 71%), BASMI (1.2+/- 13 vs. 1.6 1.2) and sacroiliitis on magnetic resonance imaging (36% vs. 47%), respectively. In patients with peripheral SpA, there were no significant differences for any of the variables analysed. CONCLUSIONS: Familial axial SpA presents symptoms at a younger age, is more frequently HLA-B27 positive and shows better spinal mobility than sporadic axial SpA; this latter presenting sacroiliitis on MRI more frequently than familial axial SpA. Apparently, no differences exist in the expression of familial or sporadic peripheral SpA. PMID- 27384503 TI - The prowess of platelets in immunity and inflammation. AB - Platelets not only serve as essential haemostatic cells, they also have important roles in immune defence and inflammation. Despite not having a nucleus, platelets contain physiologically relevant amounts of RNA, which can be spliced and translated into functional proteins. In addition, platelets have the ability to bind to numerous other cells, such as leukocytes and vascular cells. During those interactions, platelets can modulate cellular responses, resulting in e. g. inflammatory activation or apoptosis. Recent studies have demonstrated that platelets can influence the outcomes of bacterial and viral infection, as well as the extent of tissue injury after ischaemia. Platelets also carry considerable amounts of cytokines and growth factors in their secretory granules, preformed for rapid secretion. Those properties in combination with the sheer amount of platelets circulating in the blood stream make them an important force in the immune response during health and disease. In this overview, recent findings concerning those interesting properties of platelets beyond haemostasis are discussed. PMID- 27384504 TI - Correction: Assessing the potential of photosensitizing flavoproteins as tags for correlative microscopy. AB - Correction for 'Assessing the potential of photosensitizing flavoproteins as tags for correlative microscopy' by Alberto Rodriguez-Pulido et al., Chem. Commun., 2016, 52, 8405-8408. PMID- 27384502 TI - A mouse model for testing remyelinating therapies. AB - Used in combination with immunomodulatory therapies, remyelinating therapies are a viable therapeutic approach for treating individuals with multiple sclerosis. Studies of postmortem MS brains identified greater remyelination in demyelinated cerebral cortex than in demyelinated brain white matter and implicated reactive astrocytes as an inhibitor of white matter remyelination. An animal model that recapitulates these phenotypes would benefit the development of remyelination therapeutics. We have used a modified cuprizone protocol that causes a consistent and robust demyelination of mouse white matter and cerebral cortex. Spontaneous remyelination occurred significantly faster in the cerebral cortex than in white matter and reactive astrocytes were more abundant in white matter lesions. Remyelination of white matter and cerebral cortex was therapeutically enhanced by daily injections of thyroid hormone triiodothyronine (T3). In summary, we describe an in vivo demyelination/remyelination paradigm that can be powered to determine efficacy of therapies that enhance white matter and cortical remyelination. PMID- 27384505 TI - Ionoacoustic tomography of the proton Bragg peak in combination with ultrasound and optoacoustic imaging. AB - Ions provide a more advantageous dose distribution than photons for external beam radiotherapy, due to their so-called inverse depth dose deposition and, in particular a characteristic dose maximum at their end-of-range (Bragg peak). The favorable physical interaction properties enable selective treatment of tumors while sparing surrounding healthy tissue, but optimal clinical use requires accurate monitoring of Bragg peak positioning inside tissue. We introduce ionoacoustic tomography based on detection of ion induced ultrasound waves as a technique to provide feedback on the ion beam profile. We demonstrate for 20 MeV protons that ion range imaging is possible with submillimeter accuracy and can be combined with clinical ultrasound and optoacoustic tomography of similar precision. Our results indicate a simple and direct possibility to correlate, in vivo and in real-time, the conventional ultrasound echo of the tumor region with ionoacoustic tomography. Combined with optoacoustic tomography it offers a well suited pre-clinical imaging system. PMID- 27384507 TI - Quantitative analysis of biogenic polyamines in distilled drinks by direct electrospray ionization tandem mass spectrometry using a nanocontainer. AB - RATIONALE: Biogenic polyamines in drinks have been implicated in undesirable physiological effects. Methods for their detection and quantification usually involve derivatization, pre-concentration and clean-up. To assist the evaluation of the potential risk of distillates, it was important to develop a simple and fast analytical method, which is described in this study. METHODS: Biogenic polyamines were selectively encapsulated after addition of a nanocontainer, cucurbit[7]uril (50 MUM), to the distilled drink samples, which were acidified with HCl (pH 3) prior addition of the nanocontainer. The quantification of polyamines was achieved by direct infusion electrospray ionization quadrupole ion trap mass spectrometry in the multiple reaction monitoring mode, using encapsulated amantadine as internal standard, and by monitoring signals originating from their host-guest complexes. RESULTS: Six point calibration curves, ranging from 0.5 MUM to 20 MUM of polyamines in water and ethanol/water (50:50), were used to establish instrument response. The method was validated by analysis of fortified Arbutus spirits. Samples of Arbutus and grape pomace spirits were also analyzed. Linear responses were observed for all polyamines and were similar in water, hydro-alcoholic solutions and fortified Arbutus spirits. Putrescine the simple polyamine was detected only in grape pomace distillate samples. CONCLUSIONS: A quantitative method was developed for rapid and simple analysis of biogenic polyamines in distilled drinks. The detection limits depend on the ionization properties of the samples. Encapsulated amantadine can be used to probe these properties and method application. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27384506 TI - Altered expression of a two-pore domain (K2P) mechano-gated potassium channel TREK-1 in Hirschsprung's disease. AB - BACKGROUND: The pathophysiology of Hirschsprung's disease (HSCR) is not fully understood. A significant proportion of patients have persisting bowel symptoms such as constipation, soiling, and enterocolitis despite correctly performed operations. Animal data suggest that stretch-activated 2-pore domain K+ channels play a critical role in the maintenance of intestinal barrier integrity. METHODS: We investigated TREK-1 protein expression in ganglionic and aganglionic regions of HSCR patients (n = 10) vs. normal control colon (n = 10). Protein distribution was assessed by using immunofluorescence and confocal microscopy. Gene and protein expression were quantified using quantitative real-time polymerase chain reaction, western blot analysis, and densitometry. RESULTS: Confocal microscopy of the normal colon revealed strong TREK-1 channel expression in the epithelium. TREK-1-positive cells were decreased in aganglionic and ganglionic bowel compared to controls. TREK-1 gene expression levels were significantly decreased in aganglionic and ganglionic bowel compared to controls (P < 0.05). Western blotting revealed decreased TREK-1 protein expression in aganglionic and ganglionic bowel compared to controls. CONCLUSION: We demonstrate, for the first time, the expression and distribution of TREK-1 channels in the human colon. The decreased TREK-1 expression in the aganglionic and ganglionic bowel observed in HSCR may alter intestinal epithelial barrier function leading to the development of enterocolitis. PMID- 27384518 TI - Thermoplastic Elastomer-Enabled Smart Electrolyte for Thermoresponsive Self Protection of Electrochemical Energy Storage Devices. AB - Thermoresponsive smart electrolytes based on Pluronic solution are developed for active control and thermal self-protection of electrochemical energy-storage devices. Mechanistic studies reveal that the highly effective and reversible self protection behavior is attributed to the sol-gel transition of the Pluronic solution upon temperature change. The transition temperature and the degree of performance suppression can be tuned over a wide range. PMID- 27384519 TI - Pregnancy and associated events in women receiving enzyme replacement therapy for late-onset glycogen storage disease type II (Pompe disease). AB - AIM: Glycogen storage disease type II (GSD II or Pompe disease; OMIM; 232 300) is a rare autosomal recessive lysosomal storage disorder resulting from deficiency of alpha-glucosidase and accumulation of glycogen in muscle. Clinical symptoms include weakness of skeletal and respiratory muscles and, in infants, cardiomyopathy. Patients with GSD II receive infusions of recombinant alpha glucosidase (enzyme replacement therapy; ERT), which slow the progression of the disease. ERT is given to male and female patients of all ages but as yet little is documented on the effects of continuing ERT during pregnancy. The aim of this case series was therefore to ascertain the pregnancy outcomes of women with GSD II on ERT and to describe adverse events associated with pregnancy, delivery and therapy. METHODS: The medical records of eight women attending the Royal Free Hospital Lysosomal Storage Disorders Unit were reviewed. Four of the eight women had seven pregnancies over a period of 8 years. RESULTS: In this series GSD II was associated with interventional deliveries but normal neonates. Cessation of ERT in early pregnancy resulted in deterioration of maternal symptoms and emergence of allergic reactions on restarting ERT. CONCLUSION: Individualized care plans are required to ensure the best neonatal and maternal outcomes. Consideration should be given to the potential benefits to mother and fetus of continuing ERT during pregnancy. PMID- 27384520 TI - Quantitative MRI biomarkers to characterize regional left ventricular perfusion and function in nonhuman primates during dobutamine-induced stress: A reproducibility and reliability study. AB - PURPOSE: To identify reproducible and reliable noninvasive regional imaging biomarkers of cardiac function and perfusion at rest and under stress in healthy nonhuman primates (NHPs) that may be used in the future for the early characterization of preclinical heart failure models, to evaluate therapy, and for clinical translation. MATERIALS AND METHODS: Seven naive cynomolgus macaques underwent test-retest 3T cardiac MRI tagging and dual-bolus perfusion experiments. Regional cardiac function biomarkers, such as peak circumferential strain (CS), average diastolic strain-rate (DSR), contractile reserve (CR), diastolic reserve, peak torsion, and torsion reserve were quantified. Further, regional myocardial blood flow (MBF), myocardial perfusion reserve (MPR), and myocardial perfusion reserve-to-contractile reserve (MPR/CR) were also derived. Inter- and intraobserver reproducibility and test-retest reliability analyses were conducted using the reliability and generalizability coefficients including correlation coefficient (CC) and intraclass correlation coefficient (ICC). RESULTS: Overall, peak CS, DSR, and MBF are robust biomarkers at both rest and stress with moderate-good inter- and intraobserver reproducibility and test retest reliability. At rest: intra-/interobserver reproducibility (CC): peak CS (0.81/0.81), DSR (0.81/0.81), MBF (0.72/0.57), peak torsion (0.79/0.79); test retest reliability: (CC/ICC): peak CS (0.62/0.75), DSR (0.24/0.55), MBF (0.66/0.62), and peak torsion (0.79/0.78). Under stress: intra-/interobserver reproducibility (CC): peak CS (0.61/0.60), DSR (0.50/0.50), MBF (0.63/0.61), MPR (0.43/0.43), and peak torsion (0.38/0.38); test-retest reliability: (CC/ICC): peak CS (0.58/0.58), DSR (0.24/0.43), MBF (0.58/0.58), MPR (0.43/0.38), and peak torsion (0.38/0.38). CONCLUSION: We demonstrated the feasibility of using cardiac MRI to characterize left ventricular functional and perfusion responses to stress in an NHP species, and specific robust biomarkers such as peak CS, DSR, MBF, diastolic reserve, and MPR have been identified for clinical translation and drug research. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:556-569. PMID- 27384521 TI - Further evidence for deletions in 7p14.1 contributing to nonsyndromic cleft lip with or without cleft palate. AB - BACKGROUND: Nonsyndromic cleft with or without cleft palate (nsCL/P) is a common birth defect. Although genome-wide association studies (GWAS) have identified numerous risk variants, a considerable fraction of the genetic heritability remains unknown. The aim of the present study was to replicate a previous finding that de novo deletions in a 62 kb region of chromosome 7p14 are a risk factor for nsCL/P, using an independent cohort. METHODS: Data from a published case-control GWAS cohort of 399 patients and 1318 controls were used. Copy number variant (CNV) detection in the 62 kb candidate region of 7p14 was performed using QuantiSNP. Putative CNVs in probands were verified and validated by quantitative polymerase chain reaction. Segregation analyses were performed in family members for whom DNA was available. RESULTS: Within the 62 kb candidate region, a deletion of 7.4 kb showed association with nsCL/P (13/387 cases, 20/1300 controls, plowest = 0.024, odds ratio = 2.22). In all families with a sporadic case (n = 3), the deletion occurred de novo. In multiplex families, both incomplete segregation and incomplete penetrance were observed. CONCLUSION: The present data support the hypothesis that deletions at 7p14 are a common risk factor for nsCL/P. Genome-wide CNV analyses in nsCL/P cohorts are warranted to explore the functional relevance of these deletions and their contribution to nsCL/P, and to determine exact breakpoints. Birth Defects Research (Part A) 106:767-772, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27384522 TI - Triiodide-Mediated delta-Amination of Secondary C-H Bonds. AB - The Cdelta -H amination of unactivated, secondary C-H bonds to form a broad range of functionalized pyrrolidines has been developed by a triiodide (I3 (-) ) mediated strategy. By in situ 1) oxidation of sodium iodide and 2) sequestration of the transiently generated iodine (I2 ) as I3 (-) , this approach precludes undesired I2 -mediated decomposition which can otherwise limit synthetic utility to only weak C(sp(3) )-H bonds. The mechanism of this triiodide-mediated cyclization of unbiased, secondary C(sp(3) )-H bonds, by either thermal or photolytic initiation, is supported by NMR and UV/Vis data, as well as intercepted intermediates. PMID- 27384523 TI - Social Complexification and Pig (Sus scrofa) Husbandry in Ancient China: A Combined Geometric Morphometric and Isotopic Approach. AB - Pigs have played a major role in the economic, social and symbolic systems of China since the Early Neolithic more than 8,000 years ago. However, the interaction between the history of pig domestication and transformations in Chinese society since then, have not been fully explored. In this paper, we investigated the co-evolution from the earliest farming communities through to the new political and economic models of state-like societies, up to the Chinese Empire, using 5,000 years of archaeological records from the Xiawanggang (XWG) and Xinzhai (XZ) sites (Henan Province). To trace the changes of pig populations against husbandry practices, we combined the geometric morphometric analysis of dental traits with a study of the stable carbon and nitrogen isotope ratios from bone collagen. The domestication process intensified during the Neolithic Yangshao, prompted by greater selective pressure and/or better herd control against wild introgression. After that, pig farming, in XWG, relied on local livestock and a gradual change of husbandry practices overtime. This was characterized by a gentle increase in millet foddering and animal protein intake, until a complete change over to household management during the Han dynasty. The only rupture in this steady trend of husbandry occurred during the Longshan period, with the appearance of small sized and idiosyncratic pigs with specific feeding practices (relying on millet and household scraps). From three exploratory hypothesis, we explored the possibility of anti-elite pig production in XWG during the Longshan period, as a means to resist incorporation into a new economic model promoting intensified domestic production. This exploratory hypothesis is the most suitable to our dataset; however, numerous areas need to be explored further in order to adequately document the role of pigs in the rise of China's complex societies. PMID- 27384524 TI - Alkaline Phosphatase, Soluble Extracellular Adenine Nucleotides, and Adenosine Production after Infant Cardiopulmonary Bypass. AB - RATIONALE: Decreased alkaline phosphatase activity after infant cardiac surgery is associated with increased post-operative cardiovascular support requirements. In adults undergoing coronary artery bypass grafting, alkaline phosphatase infusion may reduce inflammation. Mechanisms underlying these effects have not been explored but may include decreased conversion of extracellular adenine nucleotides to adenosine. OBJECTIVES: 1) Evaluate the association between alkaline phosphatase activity and serum conversion of adenosine monophosphate to adenosine after infant cardiac surgery; 2) assess if inhibition/supplementation of serum alkaline phosphatase modulates this conversion. METHODS AND RESEARCH: Pre/post-bypass serum samples were obtained from 75 infants <4 months of age. Serum conversion of 13C5-adenosine monophosphate to 13C5-adenosine was assessed with/without selective inhibition of alkaline phosphatase and CD73. Low and high concentration 13C5-adenosine monophosphate (simulating normal/stress concentrations) were used. Effects of alkaline phosphatase supplementation on adenosine monophosphate clearance were also assessed. Changes in serum alkaline phosphatase activity were strongly correlated with changes in 13C5-adenosine production with or without CD73 inhibition (r = 0.83; p<0.0001). Serum with low alkaline phosphatase activity (<=80 U/L) generated significantly less 13C5 adenosine, particularly in the presence of high concentration 13C5-adenosine monophosphate (10.4MUmol/L vs 12.9MUmol/L; p = 0.0004). Inhibition of alkaline phosphatase led to a marked decrease in 13C5-adenosine production (11.9MUmol/L vs 2.7MUmol/L; p<0.0001). Supplementation with physiologic dose human tissue non specific alkaline phosphatase or high dose bovine intestinal alkaline phosphatase doubled 13C5-adenosine monophosphate conversion to 13C5-adenosine (p<0.0001). CONCLUSIONS: Alkaline phosphatase represents the primary serum ectonucleotidase after infant cardiac surgery and low post-operative alkaline phosphatase activity leads to impaired capacity to clear adenosine monophosphate. AP supplementation improves serum clearance of adenosine monophosphate to adenosine. These findings represent a potential therapeutic mechanism for alkaline phosphatase infusion during cardiac surgery. NEW AND NOTEWORTHY: We identify alkaline phosphatase (AP) as the primary soluble ectonucleotidase in infants undergoing cardiopulmonary bypass and show decreased capacity to clear AMP when AP activity decreases post bypass. Supplementation of AP ex vivo improves this capacity and may represent the beneficial therapeutic mechanism of AP infusion seen in phase 2 studies. PMID- 27384525 TI - Simultaneous quantitation and comparison of eight components in Jiao-ai decoction and Si-wu decoction by ultra high performance liquid chromatography with triple quadrupole tandem mass spectrometry. AB - An ultra high performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry method has been established to evaluate the variations of multiple components of Chinese herbal preparations, Jiao-ai decoction and Si wu decoction, through the simultaneous determination of eight major active compounds with a huge difference in the level of content. Chromatographic separation was achieved on a Waters Acquity UPLC BEH C18 column (2.1 * 100 mm, 1.7 MUm) with a mobile phase consisting of acetonitrile (0.1% formic acid) and water (0.1% formic acid) under gradient elution. A triple quadrupole tandem mass spectrometer was operated in positive and negative ionization modes, respectively, with multiple reaction monitoring for the detection of the eight compounds. All calibration curves showed excellent linear regressions (r > 0.99) within the test range. The precision, repeatability, and stability of the eight compounds were below 5.0% in terms of relative standard deviation. The recoveries were 97.0-102.4% with a relative standard deviation of 1.21-3.65% for all samples. In conclusion, a rapid, sensitive, precise, accurate, and reliable method has been developed for the simultaneous detection of eight active compounds in the pharmaceutical samples of Jiao-ai decoction and Si-wu decoction, which can be applied for the multicomponent comparison and further quality control. PMID- 27384526 TI - Virucidal Efficacy of a Hydrogen Peroxide Nebulization Against Murine Norovirus and Feline Calicivirus, Two Surrogates of Human Norovirus. AB - Human noroviruses (HuNoV) are amongst the leading causes of acute non-bacterial gastroenteritis in humans and can be transmitted via person-to-person contact, via contact with contaminated surfaces or by consumption of contaminated food. Contaminated surfaces in healthcare settings contribute to the transmission of viruses. No-touch automated room disinfection systems might prevent such a spread of contamination and thus their virucidal effect needs to be evaluated. The aim of this study was to assess the efficacy of a nebulization system spraying hydrogen peroxide on two main surrogates of HuNoV, namely murine norovirus (MNV) and feline calicivirus (FCV). The viruses were dried on cover glasses and on stainless steel discs and exposed to nebulization. The number of infectious viral particles and genomic copies before and after the nebulization was compared. The efficacy in reducing infectivity of both surrogates was demonstrated. For the infectious viral titre of MNV and FCV, a log10 reduction factor >=4.84 and 4.85 was observed after nebulization, respectively, for tests on cover glasses and >=3.90 and 5.30, respectively, for tests on stainless steel discs. Only low reductions in genomic copy numbers were observed for both surrogates. The nebulization of hydrogen peroxide showed a clear virucidal effect on both HuNoV surrogates, MNV and FCV, on two different carriers and the use of nebulization should be promoted in complementarity with conventional disinfection methods in healthcare settings and food processing facilities to reduce viral load and spread of contamination. PMID- 27384527 TI - Solar irradiance dictates settlement timing and intensity of marine mussels. AB - Identifying the environmental factors driving larval settlement processes is crucial to understand the population dynamics of marine invertebrates. This work aims to go a step ahead and predict larval presence and intensity. For this purpose we consider the influence of solar irradiance, wind regime and continental runoff on the settlement processes. For the first time, we conducted a 5-years weekly monitoring of Mytilus galloprovincialis settlement on artificial suspended substrates, which allowed us to search for interannual variability in the settlement patterns. Comparison between the seasonal pattern of larval settlement and solar irradiance, as well as the well-known effect of solar irradiance on water temperature and food availability, suggest that solar irradiance indirectly influences the settlement process, and support the use of this meteorological variable to predict settlement occurrence. Our results show that solar irradiance allows predicting the beginning and end of the settlement cycle a month in advance: Particularly we have observed that solar irradiance during late winter indirectly drives the timing and intensity of the settlement onset, Finally, a functional generalise additive model, which considers the influence of solar irradiance and continental runoff on the settlement process, provides an accurate prediction of settlement intensity a fortnight in advance. PMID- 27384528 TI - Clinical Pharmacokinetics and Pharmacodynamics of Biologic Therapeutics for Treatment of Systemic Lupus Erythematosus. AB - Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with potentially severe clinical manifestation that mainly affects women of child bearing age. Patients who do not respond to standard-of-care therapies, such as corticosteroids and immunosuppressants, require biologic therapeutics that specifically target a single or multiple SLE pathogenesis pathways. This review summarizes the clinical pharmacokinetic and pharmacodynamic characteristics of biologic agents that are approved, used off-label, or in the active pipeline of drug development for SLE patients. Depending on the type of target, the interacting biologics may exhibit linear (non-specific) or non-linear (target mediated) disposition profiles, with terminal half-lives varying from approximately 1 week to 1 month. Biologics given by subcutaneous administration, which offers dosing flexibility over intravenous administration, demonstrated a relatively slow absorption with a time to maximum concentration of approximately 1 day to 2 weeks and a variable bioavailability of 30-82 %. The population pharmacokinetics of monoclonal antibodies were best described by a two compartment model with central clearance and steady-state volume of distribution ranging from 0.176 to 0.215 L/day and 3.60-5.29 L, respectively. The between subject variability in pharmacokinetic parameters were moderate (20-79 %) and could be partially explained by body size. The development of linked pharmacokinetic-pharmacodynamic models incorporating SLE disease biomarkers are an attractive strategy for use in dosing regimen simulation and optimization. The relationship between efficacy/adverse events and biologic concentration should be evaluated to improve clinical trial outcomes, especially for biologics in the advanced phase of drug development. New strategies, such as model-based precision dosing dashboards, could be utilized to incorporate information collected from therapeutic drug monitoring into pharmacokinetic/pharmacodynamic models to enable individualized dosing in real time. PMID- 27384529 TI - Axial Ligation and Redox Changes at the Cobalt Ion in Cobalamin Bound to Corrinoid Iron-Sulfur Protein (CoFeSP) or in Solution Characterized by XAS and DFT. AB - A cobalamin (Cbl) cofactor in corrinoid iron-sulfur protein (CoFeSP) is the primary methyl group donor and acceptor in biological carbon oxide conversion along the reductive acetyl-CoA pathway. Changes of the axial coordination of the cobalt ion within the corrin macrocycle upon redox transitions in aqua-, methyl-, and cyano-Cbl bound to CoFeSP or in solution were studied using X-ray absorption spectroscopy (XAS) at the Co K-edge in combination with density functional theory (DFT) calculations, supported by metal content and cobalt redox level quantification with further spectroscopic methods. Calculation of the highly variable pre-edge X-ray absorption features due to core-to-valence (ctv) electronic transitions, XANES shape analysis, and cobalt-ligand bond lengths determination from EXAFS has yielded models for the molecular and electronic structures of the cobalt sites. This suggested the absence of a ligand at cobalt in CoFeSP in alpha-position where the dimethylbenzimidazole (dmb) base of the cofactor is bound in Cbl in solution. As main species, (dmb)CoIII(OH2), (dmb)CoII(OH2), and (dmb)CoIII(CH3) sites for solution Cbl and CoIII(OH2), CoII(OH2), and CoIII(CH3) sites in CoFeSP-Cbl were identified. Our data support binding of a serine residue from the reductive-activator protein (RACo) of CoFeSP to the cobalt ion in the CoFeSP-RACo protein complex that stabilizes Co(II). The absence of an alpha-ligand at cobalt not only tunes the redox potential of the cobalamin cofactor into the physiological range, but is also important for CoFeSP reactivation. PMID- 27384530 TI - Diagnostic Value of Serial Measurement of C-Reactive Protein in the Detection of a Surgical Complication after Laparoscopic Bowel Resection for Endometriosis. AB - AIMS: The study aimed to assess the diagnostic value of serial monitoring of biochemical inflammatory markers (C-reactive protein (CRP) and white blood cell (WBC) count) in the postoperative diagnosis of anastomotic leakage or ureteral injury after bowel resection for deep infiltrating endometriosis. METHODS: This is a review of prospectively collected data from 217 patients who underwent laparoscopic bowel resection for endometriosis from January 2009 to April 2015. Patients with an anastomotic leakage or ureteral injury were identified and classified. RESULTS: The frequency of anastomotic leakage requiring reoperation was 8.3%. The frequency of ureteral injury was 4.6%. Median time to diagnosis was 6 days for anastomotic leakage and 8 days for ureteral injury. The daily mean values of serum CRP were significantly higher in patients with a surgical complication starting at the second postoperative day (POD 2, p = 0.004). WBC was significantly higher (p < 0.05) on POD 2 and 3 in patients with a surgical complication. A decrease in CRP from POD 1 to 3 predicted an uncomplicated course in 92.1% of the cases. CONCLUSION: A decrease in CRP from POD 1 to 3 was an indicator of uncomplicated subsequent postoperative course. The test is recommended when early discharge after rectal resection for deep infiltrating endometriosis is considered. PMID- 27384532 TI - Calcium channel blockers are not associated with increased risk of breast cancer, study finds. PMID- 27384531 TI - Gestational Exposure to Bisphenol A Affects the Function and Proteome Profile of F1 Spermatozoa in Adult Mice. AB - BACKGROUND: Maternal exposure to the endocrine disruptor bisphenol A (BPA) has been linked to offspring reproductive abnormalities. However, exactly how BPA affects offspring fertility remains poorly understood. OBJECTIVES: The aim of the present study was to evaluate the effects of gestational BPA exposure on sperm function, fertility, and proteome profile of F1 spermatozoa in adult mice. METHODS: Pregnant CD-1 mice (F0) were gavaged with BPA at three different doses (50 MUg/kg bw/day, 5 mg/kg bw/day, and 50 mg/kg bw/day) on embryonic days 7 to 14. We investigated the function, fertility, and related processes of F1 spermatozoa at postnatal day 120. We also evaluated protein profiles of F1 spermatozoa to monitor their functional affiliation to disease. RESULTS: BPA inhibited sperm count, motility parameters, and intracellular ATP levels in a dose-dependent manner. These effects appeared to be caused by reduced numbers of stage VIII seminiferous epithelial cells in testis and decreased protein kinase A (PKA) activity and tyrosine phosphorylation in spermatozoa. We also found that BPA compromised average litter size. Proteins differentially expressed in spermatozoa from BPA treatment groups are known to play a critical role in ATP generation, oxidative stress response, fertility, and in the pathogenesis of several diseases. CONCLUSIONS: Our study provides mechanistic support for the hypothesis that gestational exposure to BPA alters sperm function and fertility via down-regulation of tyrosine phosphorylation through a PKA-dependent mechanism. In addition, we anticipate that the BPA-induced changes in the sperm proteome might be partly responsible for the observed effects in spermatozoa. Citation: Rahman MS, Kwon WS, Karmakar PC, Yoon SJ, Ryu BY, Pang MG. 2017. Gestational exposure to bisphenol-A affects the function and proteome profile of F1 spermatozoa in adult mice. Environ Health Perspect 125:238-245; http://dx.doi.org/10.1289/EHP378. PMID- 27384533 TI - A Place To Start. PMID- 27384534 TI - Capsule Commentary on Halm et al., Association Between Primary Care Visits and Colorectal Cancer Screening Outcomes in the Era of Population Health Outreach. PMID- 27384535 TI - Capsule Commentary on Jin et. al., Cost-Effectiveness of Primary HPV Testing, Cytology and Co-testing as Cervical Cancer Screening for Women above Age 30 Years. PMID- 27384536 TI - Proposals to Conduct Randomized Controlled Trials Without Informed Consent: a Narrative Review. AB - BACKGROUND: Individual informed consent from all participants is required for most randomized clinical trials (RCTs). However, some exceptions-for example, emergency research-are widely accepted. METHODS: The literature on various approaches to randomization without consent (RWOC) has never been systematically reviewed. Our goal was to provide a survey and narrative synthesis of published proposals for RWOC. We focused on proposals to randomize at least some participants in a study without first obtaining consent to randomization. This definition included studies that omitted informed consent entirely, omitted informed consent for selected patients (e.g., the control group), obtained informed consent to research but not to randomization, or only obtained informed consent to randomization after random assignment had already occurred. It omitted oral and staged consent processes that still obtain consent to randomization from all participants before randomization occurs. RESULTS: We identified ten different proposals for RWOC: two variants of cluster randomization, two variants of the Zelen design, consent to postponed information, two-stage randomized consent, cohort multiple RCT, emergency research, prompted optional randomization trials, and low-risk pragmatic RCTs without consent. CONCLUSION: Of all designs discussed here, only cluster randomized designs and emergency research are routinely used, with the justification that informed consent is infeasible in those settings. Other designs have raised concerns that they do not appropriately respect patient autonomy. Recent proposals have emphasized the importance for RWOC of demonstrating such respect through systematic patient engagement, transparency, and accountability, potentially in the context of learning health care systems. PMID- 27384537 TI - Mothers of Children with Autism have Different Rates of Cancer According to the Presence of Intellectual Disability in Their Child. AB - Autism spectrum disorder (ASD) and intellectual disability (ID) are neurodevelopmental disorders with strong genetic components. Increasingly, research attention has focused on whether genetic factors conveying susceptibility for these conditions, also influence the risk of other health conditions, such as cancer. We examined the occurrence of hospital admissions and treatment/services for cancer in mothers of children with ASD with or without ID compared with other mothers. After linking Western Australian administrative health databases, we used Cox regression to estimate the hazard ratios (HRs) of any hospitalisations and treatment/services for cancer in these groups of mothers. Mothers of children with ASD without ID had greater risk of admissions for cancer (HR 1.29 [95 % CI 1.1, 1.7]), and for treatment/services in particular (HR 1.41 [95 % CI 1.0, 2.0]), than mothers of children with no ASD/ID, while mothers of children with ASD with ID were no more likely to have a cancer-related hospital admission than other mothers. Mothers of children with autism without ID had increased risk of cancer, which may relate to common genetic pathways. PMID- 27384538 TI - Immunogenicity Assessment of Tumor Necrosis Factor Antagonists in the Clinical Laboratory. AB - BACKGROUND: Tumor necrosis factor (TNF) antagonists are increasingly used for the treatment of inflammatory and autoimmune diseases. Immunogenicity of these drugs poses therapeutic challenges such as therapeutic failure and adverse effects in a number of patients. Evaluation of clinical nonresponsiveness includes laboratory testing for drug concentrations and detecting the presence of antidrug antibodies. CONTENT: This review provides an overview of the immunogenicity of TNF antagonists and testing methodologies currently available for measuring antidrug antibody response, which decreases treatment efficacy and may result in therapeutic failure. This review summarizes methodologies such as binding assays, including ELISA and HPLC-based homogenous mobility shift assay, as well as functional cell-based assays such as reporter gene assay. Furthermore, based on the laboratory findings of testing for antidrug antibody response, as well as serum drug concentrations, an algorithm is provided for interpretation, based on the current available literature and guidelines, which may aid in determining optimal therapy after treatment failure. SUMMARY: Laboratory testing methodologies for measuring serum concentrations of TNF inhibitors and antidrug antibodies are clinically available. These methods provide an evidence-based, personalized approach for the workup of patients showing treatment failure, which saves time and resources, and contributes to improved patient care. PMID- 27384539 TI - Analytical Bias Exceeding Desirable Quality Goal in 4 out of 5 Common Immunoassays: Results of a Native Single Serum Sample External Quality Assessment Program for Cobalamin, Folate, Ferritin, Thyroid-Stimulating Hormone, and Free T4 Analyses. AB - BACKGROUND: We undertook this study to evaluate method differences for 5 components analyzed by immunoassays, to explore whether the use of method dependent reference intervals may compensate for method differences, and to investigate commutability of external quality assessment (EQA) materials. METHODS: Twenty fresh native single serum samples, a fresh native serum pool, Nordic Federation of Clinical Chemistry Reference Serum X (serum X) (serum pool), and 2 EQA materials were sent to 38 laboratories for measurement of cobalamin, folate, ferritin, free T4, and thyroid-stimulating hormone (TSH) by 5 different measurement procedures [Roche Cobas (n = 15), Roche Modular (n = 4), Abbott Architect (n = 8), Beckman Coulter Unicel (n = 2), and Siemens ADVIA Centaur (n = 9)]. The target value for each component was calculated based on the mean of method means or measured by a reference measurement procedure (free T4). Quality specifications were based on biological variation. Local reference intervals were reported from all laboratories. RESULTS: Method differences that exceeded acceptable bias were found for all components except folate. Free T4 differences from the uncommonly used reference measurement procedure were large. Reference intervals differed between measurement procedures but also within 1 measurement procedure. The serum X material was commutable for all components and measurement procedures, whereas the EQA materials were noncommutable in 13 of 50 occasions (5 components, 5 methods, 2 EQA materials). CONCLUSIONS: The bias between the measurement procedures was unacceptably large in 4/5 tested components. Traceability to reference materials as claimed by the manufacturers did not lead to acceptable harmonization. Adjustment of reference intervals in accordance with method differences and use of commutable EQA samples are not implemented commonly. PMID- 27384540 TI - The IRIDICA BAC BSI Assay: Rapid, Sensitive and Culture-Independent Identification of Bacteria and Candida in Blood. AB - Bloodstream infection (BSI) and sepsis are rising in incidence throughout the developed world. The spread of multi-drug resistant organisms presents increasing challenges to treatment. Surviving BSI is dependent on rapid and accurate identification of causal organisms, and timely application of appropriate antibiotics. Current culture-based methods used to detect and identify agents of BSI are often too slow to impact early therapy and may fail to detect relevant organisms in many positive cases. Existing methods for direct molecular detection of microbial DNA in blood are limited in either sensitivity (likely the result of small sample volumes) or in breadth of coverage, often because the PCR primers and probes used target only a few specific pathogens. There is a clear unmet need for a sensitive molecular assay capable of identifying the diverse bacteria and yeast associated with BSI directly from uncultured whole blood samples. We have developed a method of extracting DNA from larger volumes of whole blood (5 ml per sample), amplifying multiple widely conserved bacterial and fungal genes using a mismatch- and background-tolerant PCR chemistry, and identifying hundreds of diverse organisms from the amplified fragments on the basis of species-specific genetic signatures using electrospray ionization mass spectrometry (PCR/ESI-MS). We describe the analytical characteristics of the IRIDICA BAC BSI Assay and compare its pre-clinical performance to current standard-of-care methods in a collection of prospectively collected blood specimens from patients with symptoms of sepsis. The assay generated matching results in 80% of culture-positive cases (86% when common contaminants were excluded from the analysis), and twice the total number of positive detections. The described method is capable of providing organism identifications directly from uncultured blood in less than 8 hours. DISCLAIMER: The IRIDICA BAC BSI Assay is not available in the United States. PMID- 27384541 TI - Temporizin and Temporizin-1 Peptides as Novel Candidates for Eliminating Trypanosoma cruzi. AB - Tropical diseases caused by parasitic infections continue to cause socioeconomic distress worldwide. Among these, Chagas disease has become a great concern because of globalization. Caused by Trypanosoma cruzi, there is an increasing need to discover new, more effective methods to manage infections that minimize disease onset. Antimicrobial peptides represent a possible solution to this challenge. As effector molecules of the innate immune response against pathogens, they are the first line of defense found in all multi-cellular organisms. In amphibians, temporins are a large family of antimicrobial peptides found in skin secretions. Their functional roles and modes of action present unique properties that indicate possible candidates for therapeutic applications. Here, we investigated the trypanocide activity of temporizin and temporizin-1. Temporizin is an artificial, hybrid peptide containing the N-terminal region of temporin A, the pore-forming region of gramicidin and a C-terminus consisting of alternating leucine and lysine. Temporizin-1 is a modification of temporizin with a reduction in the region responsible for insertion into membranes. Their activities were evaluated in a cell permeabilization assay by flow cytometry, an LDH release assay, electron microscopy, an MTT assay and patch clamp experiments. Both temporizin and temporizin-1 demonstrated toxicity against T. cruzi with temporizin displaying slightly more potency. At concentrations up to 100 MUg/ ml, both peptides exhibited low toxicity in J774 cells, a macrophage lineage cell line, and no toxicity was observed in mouse primary peritoneal macrophages. In contrast, the peptides showed some toxicity in rat adenoma GH3 cells and Jurkat human lymphoma cells with temporizin-1 displaying lower toxicity. In summary, a shortened form of the hybrid temporizin peptide, temporizin-1, was efficient at killing T. cruzi and it has low toxicity in wild-type mammalian cells. These data suggest that temporizin-1 might be a candidate for Chagas disease therapy. PMID- 27384543 TI - A Molecular-Level Study of Metamorphosis and Strengthening of Gels by Spontaneous Polymorphic Transitions. AB - Many weak gels often undergo spontaneous transformation to form a stronger gel upon aging. Herein, the molecular-level changes that occur during the transformation of a weak gel into a strong gel are shown by using various time dependent techniques. Diol 1 forms a metastable transparent gel (TG) in a mixture of CH2 Cl2 /hexane and undergoes a fast transition to an opaque gel (OG) accompanied by gradual strengthening of the gel, as evidenced from time-dependent Tgel and rheology studies. Differential scanning calorimetry and thermogravimetric analyses suggest that these two gels correspond to two different polymorphs. By using FTIR spectroscopy and powder XRD experiments, it is shown that the TG-containing kinetic polymorph, with weakly hydrogen-bonded self-assembly, spontaneously changes into the OG containing a strongly hydrogen bonded stable polymorph and this leads to strengthening of the gel and metamorphosis. Time-dependent IR studies prove the gradual change in hydrogen bonding pattern. This is the first molecular-level study of polymorphic transitions in gels. PMID- 27384542 TI - Association of Marijuana Use With Blunted Nucleus Accumbens Response to Reward Anticipation. AB - IMPORTANCE: Marijuana use may alter ventral striatal response to reward, which might heighten susceptibility to substance use disorder. Longitudinal research is needed to determine the effects of marijuana use on neural function involved in reward response. OBJECTIVE: To determine whether marijuana use among young adults prospectively affects nucleus accumbens (NAcc) activation during reward anticipation. DESIGN, SETTING, AND PARTICIPANTS: One hundred eight young adults were recruited from the Michigan Longitudinal Study, an ongoing study of youth at high risk for substance use disorder and a contrast sample of control families. Participants underwent 3 consecutive functional magnetic resonance imaging scans at approximate ages of 20 (time 1), 22 (time 2), and 24 (time 3) years. Self report data on marijuana and other drug use occasions were collected annually since age 11 years. MAIN OUTCOMES AND MEASURES: Cross-lagged models were used to test the association of marijuana use with neural response in the NAcc to reward anticipation during a monetary incentive delay task controlling for sex, age, other substance use, and family history of substance use disorder. RESULTS: Of 108 participants, 39 (36.1%) were female and mean (SD) age at baseline was 20.1 (1.4) years. Greater marijuana use was associated with later blunted activation in the NAcc during reward anticipation (time 1 to time 2: beta = -0.26, P = .04; time 2 to time 3: beta = -0.25, P = .01). When the cross-lagged model was tested with the inclusion of previous and concurrent cigarette use, the effect of marijuana use from time 2 to time 3 remained significant (beta = -0.29; P = .005) and the effect of cigarette use was nonsignificant. CONCLUSIONS AND RELEVANCE: The findings of this study indicate that marijuana use is associated with decreased neural response in the NAcc during the anticipation of nondrug rewards. Over time, marijuana use may alter anticipatory reward processing in the NAcc, which may increase the risk for continued drug use and later addiction. PMID- 27384544 TI - B-N, B-O, and B-CN Bond Formation via Palladium-Catalyzed Cross-Coupling of B Bromo-Carboranes. AB - Carboranes are boron-rich molecules that can be functionalized through metal catalyzed cross-coupling. Here, for the first time, we report the use of bromo carboranes in palladium-catalyzed cross-coupling for efficient B-N, B-O, and unprecedented B-CN bond formation. In many cases bromo-carboranes outperform the traditionally utilized iodo-carborane species. This marked difference in reactivity is leveraged to circumvent multistep functionalization by directly coupling small nucleophiles (-OH, -NH2, and -CN) and multiple functional groups onto the boron-rich clusters. PMID- 27384545 TI - Understanding the Regulatory Roles of Natural Killer T Cells in Rheumatoid Arthritis: T Helper Cell Differentiation Dependent or Independent? AB - Rheumatoid arthritis (RA) is the most common chronic systemic autoimmune disease. This disease is thought to be caused by pathogenic T cells. Th1, Th2, Th17 and Treg cells have been implicated in the pathogenesis of RA. These Th cells differentiate from CD4+ T cells primarily due to the effects of cytokines. Natural killer T (NKT) cells are a distinct subset of lymphocytes that can rapidly secrete massive amount of cytokines, including IL-2, IL-4, IL-12 and IFN gamma. Numerous studies showed that NKT cells can influence the differentiation of CD4+ T cells via cytokines in vitro. These findings suggest that NKT cells play an important role in RA by polarizing Th1, Th2, Th17 and Treg cells. In view of the complexity of RA, we discussed whether NKT cells really influence the development of RA through regulating the differentiation of Th cells. PMID- 27384546 TI - Erratum to: The laparoscopic modified Sugarbaker technique is safe and has a low recurrence rate: a multicenter cohort study. PMID- 27384547 TI - The use of patient factors to improve the prediction of operative duration using laparoscopic cholecystectomy. AB - BACKGROUND: Reliable prediction of operative duration is essential for improving patient and care team satisfaction, optimizing resource utilization and reducing cost. Current operative scheduling systems are unreliable and contribute to costly over- and underestimation of operative time. We hypothesized that the inclusion of patient-specific factors would improve the accuracy in predicting operative duration. METHODS: We reviewed all elective laparoscopic cholecystectomies performed at a single institution between 01/2007 and 06/2013. Concurrent procedures were excluded. Univariate analysis evaluated the effect of age, gender, BMI, ASA, laboratory values, smoking, and comorbidities on operative duration. Multivariable linear regression models were constructed using the significant factors (p < 0.05). The patient factors model was compared to the traditional surgical scheduling system estimates, which uses historical surgeon specific and procedure-specific operative duration. External validation was done using the ACS-NSQIP database (n = 11,842). RESULTS: A total of 1801 laparoscopic cholecystectomy patients met inclusion criteria. Female sex was associated with reduced operative duration (-7.5 min, p < 0.001 vs. male sex) while increasing BMI (+5.1 min BMI 25-29.9, +6.9 min BMI 30-34.9, +10.4 min BMI 35-39.9, +17.0 min BMI 40 + , all p < 0.05 vs. normal BMI), increasing ASA (+7.4 min ASA III, +38.3 min ASA IV, all p < 0.01 vs. ASA I), and elevated liver function tests (+7.9 min, p < 0.01 vs. normal) were predictive of increased operative duration on univariate analysis. A model was then constructed using these predictive factors. The traditional surgical scheduling system was poorly predictive of actual operative duration (R 2 = 0.001) compared to the patient factors model (R 2 = 0.08). The model remained predictive on external validation (R 2 = 0.14).The addition of surgeon as a variable in the institutional model further improved predictive ability of the model (R 2 = 0.18). CONCLUSION: The use of routinely available pre-operative patient factors improves the prediction of operative duration during cholecystectomy. PMID- 27384549 TI - Multivariate Chemical Image Fusion of Vibrational Spectroscopic Imaging Modalities. AB - Chemical image fusion refers to the combination of chemical images from different modalities for improved characterisation of a sample. Challenges associated with existing approaches include: difficulties with imaging the same sample area or having identical pixels across microscopic modalities, lack of prior knowledge of sample composition and lack of knowledge regarding correlation between modalities for a given sample. In addition, the multivariate structure of chemical images is often overlooked when fusion is carried out. We address these challenges by proposing a framework for multivariate chemical image fusion of vibrational spectroscopic imaging modalities, demonstrating the approach for image registration, fusion and resolution enhancement of chemical images obtained with IR and Raman microscopy. PMID- 27384548 TI - The effect of statins on prostate cancer recurrence and mortality after definitive therapy: a systematic review and meta-analysis. AB - In this work, we aim to further analyze the association of statins use with biochemical recurrence (BCR) of prostate cancer (PCa) and PCa-specific mortality after definitive therapy. A systematic literature search of PubMed, MEDLINE, and EMBASE through Jul 2015 was conducted. Pooled Hazard ratio (HR) estimates with corresponding 95% confidence intervals (CIs) were calculated using random-effects model. STATA version 10 (Stata corporation, college station, TX) was employed to conduct all statistical analyses. A total of 22 and 8 studies contributed to the biochemical recurrence analysis and PCa-specific mortality, respectively. 13 trials were included for BCR-free survival analysis. The combined result showed statins users had lowered 12% BCR risk of PCa compared with non-users (HR = 0.88, 95%CI: 0.765-0.998) (p < 0.05). The association was null among the men who underwent radical prostatectomy as primary therapy (HR = 0.96, 95%CI: 0.83-1.09), while the improved outcomes had be seen among patients who received radiation therapy (HR = 0.67, 95%CI: 0.48-0.86). After excluding the patients undergoing ADT, participants did not benefit from statins use (HR = 0.94, 95%CI: 0.77-1.11). Meanwhile, long-term statins using did not alter recurrence risk. A lower risk of prostate cancer-specific mortality was observed among statins users (HR = 0.68, 95%CI: 0.56-0.80). There was a plausible trend towards increasing the BCR-free survival rate among statins users. PMID- 27384550 TI - Carlina acaulis Exhibits Antioxidant Activity and Counteracts Abeta Toxicity in Caenorhabditis elegans. AB - Carlina acaulis is a medicinal plant that has shown antioxidant activity in in vitro studies, but to date no corresponding in vivo data is available. Therefore, in the present study the antioxidant activity and its impact in counteracting Abeta toxicity were studied in the Caenorhabditis elegans model. A dichloromethane extract of the roots of C. acaulis was prepared and characterised via gas-liquid-chromatography/mass-spectrometry (GLC-MS). The in vitro antioxidant activity was confirmed via 2,2-diphenyl-1-picrylhydracyl assay. The extract was further separated by thin layer chromatography into two fractions, one of which was a fraction of the dichloromethane extract of C. acaulis containing mostly Carlina oxide (CarOx). Different strains of C. elegans were employed to study the expression of hsp-16.2p::GFP as a marker for oxidative stress, delocalisation of the transcription factor DAF-16 as a possible mechanism of antioxidant activity, the effect of the drug under lethal oxidative stress, and the effect against beta-amyloid (Abeta) toxicity in a paralysis assay. The C. acaulis extract and CarOx showed high antioxidant activity (stress reduction by 47% and 64%, respectively) in C. elegans and could activate the transcription factor DAF-16 which directs the expression of anti-stress genes. In paralysis assay, only the total extract was significantly active, delaying paralysis by 1.6 h. In conclusion, in vivo antioxidant activity was shown for C. acaulis for the first time in the C. elegans model. The active antioxidant compound is Carlina oxide. This activity, however, is not sufficient to counteract Abeta toxicity. Other mechanisms and possibly other active compounds are involved in this effect. PMID- 27384551 TI - Controlled Release of Nor-beta-lapachone by PLGA Microparticles: A Strategy for Improving Cytotoxicity against Prostate Cancer Cells. AB - Prostate cancer is one of the most common malignant tumors in males and it has become a major worldwide public health problem. This study characterizes the encapsulation of Nor-beta-lapachone (NbetaL) in poly(d,l-lactide-co-glycolide) (PLGA) microcapsules and evaluates the cytotoxicity of the resulting drug-loaded system against metastatic prostate cancer cells. The microcapsules presented appropriate morphological features and the presence of drug molecules in the microcapsules was confirmed by different methods. Spherical microcapsules with a size range of 1.03 +/- 0.46 MUm were produced with an encapsulation efficiency of approximately 19%. Classical molecular dynamics calculations provided an estimate of the typical adsorption energies of NbetaL on PLGA. Finally, the cytotoxic activity of NbetaL against PC3M human prostate cancer cells was demonstrated to be significantly enhanced when delivered by PLGA microcapsules in comparison with the free drug. PMID- 27384552 TI - Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3Kbeta Inhibitors. AB - A novel series of PI3Kbeta (Phosphatidylinositol-3-kinases beta subunit) inhibitors with the structure of benzothiazole scaffold have been designed and synthesized. All the compounds have been evaluated for inhibitory activities against PI3Kalpha, beta, gamma, delta and mTOR (Mammalian target of rapamycin). Two superior compounds have been further evaluated for the IC50 values against PI3Ks/mTOR. The most promising compound 11 displays excellent anti-proliferative activity and selectivity in multiple cancer cell lines, especially in the prostate cancer cell line. Docking studies indicate the morpholine group in 2 position of benzothiazole is necessary for the potent antitumor activity, which confirms our design is reasonable. PMID- 27384553 TI - Design and Stereochemical Research (DFT, ECD and Crystal Structure) of Novel Bedaquiline Analogs as Potent Antituberculosis Agents. AB - A series of bedaquiline analogs containing H-bond donors were designed as anti Mycobacterium tuberculosis drugs. A pair of diastereoisomers (R/S- and S/S isomers) was selected from these designed compounds for synthetic and stereochemical research. The title compounds were synthesized from chiral precursors for the first time and the absolute configurations (ACs) were determined by electronic circular dichroism (ECD) with quantum chemical calculations. Moreover, a single crystal of the S/S compound was obtained for X ray diffraction analysis, and the crystal structure showed high consistency with the geometry, confirming the reliability of ACs obtained by ECD analyses and theoretical simulation. Furthermore, the effect of stereochemistry on the anti tuberculosis activity was investigated. The MICs of the R/S- and S/S-isomers against Mycobacterium phlei 1180 are 9.6 and 32.1 MUg.mL(-1), respectively. Finally, molecular docking was carried out to evaluate the inhibitory nature and binding mode differences between diastereoisomers. PMID- 27384554 TI - Retraction: A. Amedei et al. Multiple Sclerosis: The Role of Cytokines in Pathogenesis and in Therapies. Int. J. Mol. Sci. 2012, 13, 13438-13460. AB - We have been made aware that the title paper [1] contains text taken verbatim from previously published articles by Shyi-Jou Chen et al. [2] and Ghislain Opdenakker and Jo Van Damme [3].[...]. PMID- 27384555 TI - Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins. AB - Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel's ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators. PMID- 27384556 TI - Molecular Signals Controlling the Inhibition of Nodulation by Nitrate in Medicago truncatula. AB - The presence of nitrogen inhibits legume nodule formation, but the mechanism of this inhibition is poorly understood. We found that 2.5 mM nitrate and above significantly inhibited nodule initiation but not root hair curling in Medicago trunatula. We analyzed protein abundance in M. truncatula roots after treatment with either 0 or 2.5 mM nitrate in the presence or absence of its symbiont Sinorhizobium meliloti after 1, 2 and 5 days following inoculation. Two dimensional gel electrophoresis combined with mass spectrometry was used to identify 106 differentially accumulated proteins responding to nitrate addition, inoculation or time point. While flavonoid-related proteins were less abundant in the presence of nitrate, addition of Nod gene-inducing flavonoids to the Sinorhizobium culture did not rescue nodulation. Accumulation of auxin in response to rhizobia, which is also controlled by flavonoids, still occurred in the presence of nitrate, but did not localize to a nodule initiation site. Several of the changes included defense- and redox-related proteins, and visualization of reactive oxygen species indicated that their induction in root hairs following Sinorhizobium inoculation was inhibited by nitrate. In summary, the presence of nitrate appears to inhibit nodulation via multiple pathways, including changes to flavonoid metabolism, defense responses and redox changes. PMID- 27384558 TI - Mechanisms Underlying the Immune Response Generated by an Oral Vibrio cholerae Vaccine. AB - Mechanistic details underlying the resulting protective immune response generated by mucosal vaccines remain largely unknown. We investigated the involvement of Toll-like receptor signaling in the induction of humoral immune responses following oral immunization with Dukoral, comparing wild type mice with TLR-2-, TLR-4-, MyD88- and Trif-deficient mice. Although all groups generated similar levels of IgG antibodies, the proliferation of CD4+ T-cells in response to V. cholerae was shown to be mediated via MyD88/TLR signaling, and independently of Trif signaling. The results demonstrate differential requirements for generation of immune responses. These results also suggest that TLR pathways may be modulators of the quality of immune response elicited by the Dukoral vaccine. Determining the critical signaling pathways involved in the induction of immune response to this vaccine would be beneficial, and could contribute to more precisely-designed versions of other oral vaccines in the future. PMID- 27384557 TI - Aberrant Lipid Metabolism Promotes Prostate Cancer: Role in Cell Survival under Hypoxia and Extracellular Vesicles Biogenesis. AB - Prostate cancer (PCa) is the leading malignancy among men in United States. Recent studies have focused on the identification of novel metabolic characteristics of PCa, aimed at devising better preventive and therapeutic approaches. PCa cells have revealed unique metabolic features such as higher expression of several enzymes associated with de novo lipogenesis, fatty acid up take and beta-oxidation. This aberrant lipid metabolism has been reported to be important for PCa growth, hormone-refractory progression and treatment resistance. Furthermore, PCa cells effectively use lipid metabolism under adverse environmental conditions for their survival advantage. Specifically, hypoxic cancer cells accumulate higher amount of lipids through a combination of metabolic alterations including high glutamine and fatty acid uptake, as well as decreased fatty acid oxidation. These stored lipids serve to protect cancer cells from oxidative and endoplasmic reticulum stress, and play important roles in fueling cancer cell proliferation following re-oxygenation. Lastly, cellular lipids have also been implicated in extracellular vesicle biogenesis, which play a vital role in intercellular communication. Overall, the new understanding of lipid metabolism in recent years has offered several novel targets to better target and manage clinical PCa. PMID- 27384559 TI - Digital Gene Expression Analysis of Ponkan Mandarin (Citrus reticulata Blanco) in Response to Asia Citrus Psyllid-Vectored Huanglongbing Infection. AB - Citrus Huanglongbing (HLB), the most destructive citrus disease, can be transmitted by psyllids and diseased budwoods. Although the final symptoms of the two main HLB transmission ways were similar and hard to distinguish, the host responses might be different. In this study, the global gene changes in leaves of ponkan (Citrus reticulata) mandarin trees following psyllid-transmission of HLB were analyzed at the early symptomatic stage (13 weeks post inoculation, wpi) and late symptomatic stage (26 wpi) using digital gene expression (DGE) profiling. At 13 wpi, 2452 genes were downregulated while only 604 genes were upregulated in HLB infected ponkan leaves but no pathway enrichment was identified. Gene function analysis showed impairment in defense at the early stage of infection. At late stage of 26 wpi, however, differentially expressed genes (DEGs) involved in carbohydrate metabolism, plant defense, hormone signaling, secondary metabolism, transcription regulation were overwhelmingly upregulated, indicating that the defense reactions were eventually activated. The results indicated that HLB bacterial infection significantly influenced ponkan gene expression, and a delayed response of the host to the fast growing bacteria might be responsible for its failure in fighting against the bacteria. PMID- 27384560 TI - Intra-Articular Injections of Platelet-Rich Plasma versus Hyaluronic Acid in the Treatment of Osteoarthritic Knee Pain: A Randomized Clinical Trial in the Context of the Spanish National Health Care System. AB - Intra-articular injection of platelet-rich plasma (PRP) has been established as a suitable treatment for knee osteoarthritis. Here, we present a double-blind randomized controlled clinical trial, conducted in a public Hospital of the Spanish National Health Care System, to evaluate the efficacy of injecting autologous PRP versus hyaluronic acid (HA) in knee osteoarthritis. PRP was manufactured in Malaga's Regional Blood Center (Spain). Patients that met the eligibility criteria were randomized into a PRP group or a HA group. Pain and functional improvements were assessed pre- and post-treatment (three and six months follow-up) using the Visual Analogue Scale (VAS); the Knee and Osteoarthritis Outcome System (KOOS) scale and the European Quality of Life scale (EUROQOL). Both groups presented pain reduction at six months. The VAS scores for the PRP group improved by at least 50% from their initial value, particularly at three months following the final infiltration, with results resembling those of the HA group at six months. PRP was more effective in patients with lower osteoarthritis grades. Both treatments improved pain in knee osteoarthritis patients without statistically significant differences between them. However, PRP injection was proved to improve pain three months after the final infiltration and to be more effective in lower osteoarthritis grades. PMID- 27384561 TI - Determination of Free-Form and Peptide Bound Pyrraline in the Commercial Drinks Enriched with Different Protein Hydrolysates. AB - Pyrraline, a causative factor for the recent epidemics of diabetes and cardiovascular disease, is also employed as an indicator to evaluate heat damage and formation of advanced glycation end-products (AGEs) in foods. Peptide enriched drinks (PEDs) are broadly consumed worldwide due to rapid rate of absorption and perceived health effects. It can be hypothesized that PED is an important source of pyrraline, especially peptide bound pyrraline (Pep-Pyr). In this study we determined free-form pyrraline (Free-Pyr) and Pep-Pyr in drinks enriched with whey protein hydrolysate (WPH), soy protein hydrolysate (SPH) and collagen protein hydrolysate (CPH). A detection method was developed using ultrahigh-performance liquid chromatography with UV-visible detector coupled with tandem mass spectrometry after solid-phase extraction (SPE). The SPE led to excellent recovery rates ranging between 93.2% and 98.5% and a high reproducibility with relative standard deviations (RSD) of <5%. The limits of detection and quantification obtained were 30.4 and 70.3 ng/mL, respectively. Pep Pyr was identified as the most abundant form (above 96 percent) of total pyrraline, whereas Free-Pyr was present in a small proportion (less than four percent) of total pyrraline. The results indicate that PED is an important extrinsic source of pyrraline, especially Pep-Pyr. As compared with CPH- and SPH enriched drinks, WPH-enriched drinks contained high content of Pep-Pyr. The Pep Pyr content is associated with the distribution of peptide lengths and the amino acid compositions of protein in PEDs. PMID- 27384563 TI - LEA Detection and Tracking Method for Color-Independent Visual-MIMO. AB - Communication performance in the color-independent visual-multiple input multiple output (visual-MIMO) technique is deteriorated by light emitting array (LEA) detection and tracking errors in the received image because the image sensor included in the camera must be used as the receiver in the visual-MIMO system. In this paper, in order to improve detection reliability, we first set up the color space-based region of interest (ROI) in which an LEA is likely to be placed, and then use the Harris corner detection method. Next, we use Kalman filtering for robust tracking by predicting the most probable location of the LEA when the relative position between the camera and the LEA varies. In the last step of our proposed method, the perspective projection is used to correct the distorted image, which can improve the symbol decision accuracy. Finally, through numerical simulation, we show the possibility of robust detection and tracking of the LEA, which results in a symbol error rate (SER) performance improvement. PMID- 27384564 TI - On the Use of a Signal Quality Index Applying at Tracking Stage Level to Assist the RAIM System of a GNSS Receiver. AB - In this work, a novel signal processing method is proposed to assist the Receiver Autonomous Integrity Monitoring (RAIM) module used in a receiver of Global Navigation Satellite Systems (GNSS) to improve the integrity of the estimated position. The proposed technique represents an evolution of the Multipath Distance Detector (MPDD), thanks to the introduction of a Signal Quality Index (SQI), which is both a metric able to evaluate the goodness of the signal, and a parameter used to improve the performance of the RAIM modules. Simulation results show the effectiveness of the proposed method. PMID- 27384562 TI - Less Is More: Substrate Reduction Therapy for Lysosomal Storage Disorders. AB - Lysosomal storage diseases (LSDs) are a group of rare, life-threatening genetic disorders, usually caused by a dysfunction in one of the many enzymes responsible for intralysosomal digestion. Even though no cure is available for any LSD, a few treatment strategies do exist. Traditionally, efforts have been mainly targeting the functional loss of the enzyme, by injection of a recombinant formulation, in a process called enzyme replacement therapy (ERT), with no impact on neuropathology. This ineffectiveness, together with its high cost and lifelong dependence is amongst the main reasons why additional therapeutic approaches are being (and have to be) investigated: chaperone therapy; gene enhancement; gene therapy; and, alternatively, substrate reduction therapy (SRT), whose aim is to prevent storage not by correcting the original enzymatic defect but, instead, by decreasing the levels of biosynthesis of the accumulating substrate(s). Here we review the concept of substrate reduction, highlighting the major breakthroughs in the field and discussing the future of SRT, not only as a monotherapy but also, especially, as complementary approach for LSDs. PMID- 27384565 TI - Exchange Bias Tuning for Magnetoresistive Sensors by Inclusion of Non-Magnetic Impurities. AB - The fine control of the exchange coupling strength and blocking temperature ofexchange bias systems is an important requirement for the development of magnetoresistive sensors with two pinned electrodes. In this paper, we successfully tune these parameters in top- and bottom-pinned systems, comprising 5 nm thick Co40Fe40B20 and 6.5 nm thick Ir22Mn78 films. By inserting Ru impurities at different concentrations in the Ir22Mn78 layer, blocking temperatures ranging from 220 degrees C to 100 degrees C and exchange bias fields from 200 Oe to 60 Oe are obtained. This method is then applied to the fabrication of sensors based on magnetic tunneling junctions consisting of a pinned synthetic antiferromagnet reference layer and a top-pinned sensing layer. This work paves the way towards the development of new sensors with finely tuned magnetic anisotropies. PMID- 27384566 TI - A Channelization-Based DOA Estimation Method for Wideband Signals. AB - In this paper, we propose a novel direction of arrival (DOA) estimation method for wideband signals with sensor arrays. The proposed method splits the wideband array output into multiple frequency sub-channels and estimates the signal parameters using a digital channelization receiver. Based on the output sub channels, a channelization-based incoherent signal subspace method (Channelization-ISM) and a channelization-based test of orthogonality of projected subspaces method (Channelization-TOPS) are proposed. Channelization-ISM applies narrowband signal subspace methods on each sub-channel independently. Then the arithmetic mean or geometric mean of the estimated DOAs from each sub channel gives the final result. Channelization-TOPS measures the orthogonality between the signal and the noise subspaces of the output sub-channels to estimate DOAs. The proposed channelization-based method isolates signals in different bandwidths reasonably and improves the output SNR. It outperforms the conventional ISM and TOPS methods on estimation accuracy and dynamic range, especially in real environments. Besides, the parallel processing architecture makes it easy to implement on hardware. A wideband digital array radar (DAR) using direct wideband radio frequency (RF) digitization is presented. Experiments carried out in a microwave anechoic chamber with the wideband DAR are presented to demonstrate the performance. The results verify the effectiveness of the proposed method. PMID- 27384567 TI - Design of Helical Capacitance Sensor for Holdup Measurement in Two-Phase Stratified Flow: A Sinusoidal Function Approach. AB - A 360 degrees twisted helical capacitance sensor was developed for holdup measurement in horizontal two-phase stratified flow. Instead of suppressing nonlinear response, the sensor was optimized in such a way that a 'sine-like' function was displayed on top of the linear function. This concept of design had been implemented and verified in both software and hardware. A good agreement was achieved between the finite element model of proposed design and the approximation model (pure sinusoidal function), with a maximum difference of +/ 1.2%. In addition, the design parameters of the sensor were analysed and investigated. It was found that the error in symmetry of the sinusoidal function could be minimized by adjusting the pitch of helix. The experiments of air-water and oil-water stratified flows were carried out and validated the sinusoidal relationship with a maximum difference of +/-1.2% and +/-1.3% for the range of water holdup from 0.15 to 0.85. The proposed design concept therefore may pose a promising alternative for the optimization of capacitance sensor design. PMID- 27384568 TI - Multi-Sensor Integration to Map Odor Distribution for the Detection of Chemical Sources. AB - This paper addresses the problem of mapping odor distribution derived from a chemical source using multi-sensor integration and reasoning system design. Odor localization is the problem of finding the source of an odor or other volatile chemical. Most localization methods require a mobile vehicle to follow an odor plume along its entire path, which is time consuming and may be especially difficult in a cluttered environment. To solve both of the above challenges, this paper proposes a novel algorithm that combines data from odor and anemometer sensors, and combine sensors' data at different positions. Initially, a multi sensor integration method, together with the path of airflow was used to map the pattern of odor particle movement. Then, more sensors are introduced at specific regions to determine the probable location of the odor source. Finally, the results of odor source location simulation and a real experiment are presented. PMID- 27384569 TI - Odanacatib, a Cathepsin K Cysteine Protease Inhibitor, Kills Hookworm In Vivo. AB - Hookworm infection is chief among soil-transmitted helminthiases (STHs) for the chronic morbidly inflicted. Deworming via mass drug administration (MDA) programs most often employs single doses of benzimidazole drugs to which resistance is a constant threat. To discover new drugs, we employ a hamster model of hookworm infection with Ancylostoma ceylanicum and use albendazole (ABZ; 10 mg/kg orally) as the gold standard therapy. We previously showed that a single oral 100 mg/kg dose of the cathepsin cysteine protease (CP) inhibitor, K11777, offers near cure of infection that is associated with a 95% reduction in the parasite's resident CP activity. We confirm these findings here and demonstrate that odanacatib (ODN), Merck's cathepsin K inhibitor and post-clinical Phase III drug candidate for treatment of osteoporosis, decreases worm burden by 73% at the same dose with a 51% reduction in the parasite's CP activity. Unlike K11777, ODN is a modest inhibitor of both mammalian cathepsin B and the predominant cathepsin B-like activity measureable in hookworm extracts. ODN's somewhat unexpected efficacy, therefore, may be due to its excellent pharmacokinetic (PK) profile which allows for sustained plasma exposure and, possibly, sufficient perturbation of hookworm cathepsin B activity to be detrimental to survival. Accordingly, identifying a CP inhibitor(s) that combines the inhibition potency of K11777 and the PK attributes of ODN could lead to a drug that is effective at a lower dose. Achieving this would potentially provide an alternative or back-up to the current anti-hookworm drug, albendazole. PMID- 27384570 TI - Heparin: Past, Present, and Future. AB - Heparin, the most widely used anticoagulant drug in the world today, remains an animal-derived product with the attendant risks of adulteration and contamination. A contamination crisis in 2007-2008 increased the impetus to provide non-animal-derived sources of heparin, produced under cGMP conditions. In addition, recent studies suggest that heparin may have significant antineoplastic activity, separate and distinct from its anticoagulant activity, while other studies indicate a role for heparin in treating inflammation, infertility, and infectious disease. A variety of strategies have been proposed to produce a bioengineered heparin. In this review, we discuss several of these strategies including microbial production, mammalian cell production, and chemoenzymatic modification. We also propose strategies for creating "designer" heparins and heparan-sulfates with various biochemical and physiological properties. PMID- 27384571 TI - Functions of Cationic Host Defense Peptides in Immunity. AB - Cationic host defense peptides are a widely distributed family of immunomodulatory molecules with antimicrobial properties. The biological functions of these peptides include the ability to influence innate and adaptive immunity for efficient resolution of infections and simultaneous modulation of inflammatory responses. This unique dual bioactivity of controlling infections and inflammation has gained substantial attention in the last three decades and consequent interest in the development of these peptide mimics as immunomodulatory therapeutic candidates. In this review, we summarize the current literature on the wide range of functions of cationic host defense peptides in the context of the mammalian immune system. PMID- 27384572 TI - Economic Burden of Hospitalization Due to Injuries in North India: A Cohort Study. AB - There is little documentation of the potential catastrophic effects of injuries on families due to out of pocket (OOP) expenditure for medical care. Patients who were admitted for at least one night in a tertiary care hospital of Chandigarh city due to injury were recruited and were followed-up at 1, 2 and 12 months after discharge to collect information on OOP expenditure. Out of the total 227 patients, 60% (137/227) had sustained road traffic injuries (RTI). The average OOP expenditure per hospitalisation and up to 12 months post discharge was USD 388 (95% CI: 332-441) and USD 1046 (95% CI: 871-1221) respectively. Mean OOP expenditure for RTI and non-RTI cases during hospitalisation was USD 400 (95% CI: 344-456) and USD 369 (95% CI: 313-425) respectively. The prevalence of catastrophic expenditure was 30%, and was significantly higher among those belonging to the lowest income quartile (OR-26.50, 95% CI: 6.70-105.07, p-value: <0.01) and with an inpatient stay greater than 7 days (OR-10.60, 95% CI: 4.21 26.64, p-value: <0.01). High OOP expenditure for treatment of injury puts a significant economic burden on families. Measures aimed at increasing public health spending for prevention of injury and providing financial risk protection are urgently required in India. PMID- 27384574 TI - Integrating Health Research into Disaster Response: The New NIH Disaster Research Response Program. AB - The need for high quality and timely disaster research has been a topic of great discussion over the past several years. Recent high profile incidents have exposed gaps in knowledge about the health impacts of disasters or the benefits of specific interventions-such was the case with the 2010 Gulf Oil Spill and recent events associated with lead-contaminated drinking water in Flint, Michigan, and the evolving health crisis related to Zika virus disease. Our inability to perform timely research to inform the community about health and safety risks or address specific concerns further heightens anxiety and distrust. Since nearly all disasters, whether natural or man-made, have an environmental health component, it is critical that specialized research tools and trained researchers be readily available to evaluate complex exposures and health effects, especially for vulnerable sub-populations such as the elderly, children, pregnant women, and those with socioeconomic and environmental disparities. In response, the National Institute of Environmental Health Science has initiated a Disaster Research Response Program to create new tools, protocols, networks of researchers, training exercises, and outreach involving diverse groups of stakeholders to help overcome the challenges of disaster research and to improve our ability to collect vital information to reduce the adverse health impacts and improve future preparedness. PMID- 27384573 TI - Sugar-Sweetened Beverage Consumption Is Adversely Associated with Childhood Attention Deficit/Hyperactivity Disorder. AB - Attention deficit/hyperactivity disorder (ADHD) is one of the most common childhood neurobehavioral conditions. Evidence of the negative effects of sugar sweetened beverages (SSBs) on mental health has not been convincing, although a few studies have found an association between high SSB levels and attention problems in children. This study aimed to test the hypothesis that SSB consumption is associated with ADHD among children. Doctor-diagnosed ADHD cases (n = 173) and non-ADHD controls (n = 159) between age 4 to 15 were recruited. SSB consumption, socio-demographic and lifestyle characteristics of the children, as well as of their mothers' characteristics during pregnancy, were collected using a questionnaire. Blood lead levels and polymorphisms of two commonly verified dopaminergic-related genes (the D4 dopamine receptor gene DRD4 and the dopamine transporter gene DAT1) were also analyzed. There was a dose-response relationship between SSB consumption and ADHD. After covariates were adjusted, children who consumed SSBs at moderate levels and high levels had 1.36 and 3.69 odds, respectively, of having ADHD, compared with those who did not consume SSBs (p for trend < 0.05). Similar results were obtained when females were excluded. Our findings highlighted the adverse correlation between SSB consumption and ADHD and indicated a dose-response effect even after covariates were adjusted. PMID- 27384575 TI - Noise Exposure of Teachers in Nursery Schools-Evaluation of Measures for Noise Reduction When Dropping DUPLO Toy Bricks into Storage Cases by Sound Analyses. AB - BACKGROUND: Although noise is one of the leading work-related health risk factors for teachers, many nursery schools lack sufficient noise reduction measures. METHODS: This intervention study evaluated the noise exposure of nursery school teachers when dropping DUPLO toy bricks into storage cases. Sound analyses of the impact included assessment of the maximum sound pressure level (LAFmax) as well as frequency analyses with 1/3 octave band filter. For the purpose of standardization, a customized gadget was developed. Recordings were performed in 11 cases of different materials and designs to assess the impact on sound level reduction. Thereby, the acoustic effects of three damping materials (foam rubber, carpet, and PU-foam) were investigated. RESULTS: The lowest LAFmax was measured in cases consisting of "metal grid" (90.71 dB) or of a woven willow "basket" (91.61 dB), whereas a case of "aluminium" (103.34 dB) generated the highest impact LAFmax. The frequency analyses determined especially low LAFmax in the frequency bands between 80 and 2500 Hz in cases designs "metal grid" and "basket". The insertion of PU-foam achieved the most significant attenuation of LAFmax (-13.88 dB) and, in the frequency analyses, the best sound damping. CONCLUSION: The dropping of DUPLO bricks in cases contributes to the high noise level in nursery schools, but measured LAFmax show no evidence for the danger of acute hearing loss. However, continuous exposure may lead to functional impairment of the hair cells and trigger stress reactions. We recommend noise reduction by utilizing cases of woven "basket" with an insert of PU-foam. PMID- 27384576 TI - The Seoul Metropolitan Lifestyle Intervention Program and Metabolic Syndrome Risk: A Retrospective Database Study. AB - Since 2011, the Seoul Metabolic Syndrome Management (SMESY) program has been employed as a community-wide, lifestyle modification intervention in Seoul, Korea. We aimed to determine if the SMESY intervention would be significantly associated with improvements in metabolic syndrome (MetS) risk factors. This retrospective database study included data from 25,449 participants aged 30-64 years between 1 January 2013 and 30 June 2013. In the SMESY program, 3 risk stratified groups by the number of MetS factors were followed for 12 months with different intensity and timeframe of intervention. Among the high-(n = 7116) and moderate-risk groups (n = 14,762), all MetS factors (except triglycerides among the moderate-risk group) as well as MetS z-scores significantly improved over 12 months (all p < 0.05). Among the low-risk group (n = 3571), all factors aggravated significantly over 12 months (all p < 0.05). We observed temporal associations between the implementation of the SMESY program and improvements in MetS risk factors. However, such improvements differed by risk-stratified group, being most robust for the high-risk group, modest for the moderate-risk group, and aggravated for the low-risk group. Thus, more intensive interventions targeting different risk-stratified groups are needed, given a better understanding of the increase in risk factors observed in the low-risk group. PMID- 27384578 TI - Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines. AB - Viral vaccine vectors have shown to be effective in inducing a robust immune response against the vaccine antigen. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising vaccine vector against human and veterinary pathogens. Avirulent NDV strains LaSota and B1 have long track records of safety and efficacy. Therefore, use of these strains as vaccine vectors is highly safe in avian and non-avian species. NDV replicates efficiently in the respiratory track of the host and induces strong local and systemic immune responses against the foreign antigen. As a vaccine vector, NDV can accommodate foreign sequences with a good degree of stability and as a RNA virus, there is limited possibility for recombination with host cell DNA. Using NDV as a vaccine vector in humans offers several advantages over other viral vaccine vectors. NDV is safe in humans due to host range restriction and there is no pre-existing antibody to NDV in the human population. NDV is antigenically distinct from common human pathogens. NDV replicates to high titer in a cell line acceptable for human vaccine development. Therefore, NDV is an attractive vaccine vector for human pathogens for which vaccines are currently not available. NDV is also an attractive vaccine vector for animal pathogens. PMID- 27384579 TI - Bioelectrical Impedance Vector Analysis and Muscular Fitness in Healthy Men. AB - Muscle strength can define the general muscular fitness (MF) measurable through hand-grip strength (HG), which is a factor that relates to the health of people of different ages. In this study we evaluated the muscle strength together with a bioimpedance electric analysis in 223 healthy Colombian adult subjects. The bioelectrical impedance vector analysis (BIVA) was conducted to determine the resistance (R), reactance (Xc) and phase angle (PhA). We classified the subjects into three groups (for tertiles), obtaining lower values of R and Xc in subjects with lower HG, plus a high correlation between PhA and HG. An increase in the level of PhA is associated with a high level of MF in a sample of healthy Latin American adult men. The BIVA's parameters and PhA are a potentially effective preventive measure to be integrated into routine screening in the clinical setting. PMID- 27384577 TI - Regulation of Stress Responses and Translational Control by Coronavirus. AB - Similar to other viruses, coronavirus infection triggers cellular stress responses in infected host cells. The close association of coronavirus replication with the endoplasmic reticulum (ER) results in the ER stress responses, which impose a challenge to the viruses. Viruses, in turn, have come up with various mechanisms to block or subvert these responses. One of the ER stress responses is inhibition of the global protein synthesis to reduce the amount of unfolded proteins inside the ER lumen. Viruses have evolved the capacity to overcome the protein translation shutoff to ensure viral protein production. Here, we review the strategies exploited by coronavirus to modulate cellular stress response pathways. The involvement of coronavirus-induced stress responses and translational control in viral pathogenesis will also be briefly discussed. PMID- 27384580 TI - The Effect of Post-Resistance Exercise Amino Acids on Plasma MCP-1 and CCR2 Expression. AB - The recruitment and infiltration of classical monocytes into damaged muscle is critical for optimal tissue remodeling. This study examined the effects of an amino acid supplement on classical monocyte recruitment following an acute bout of lower body resistance exercise. Ten resistance-trained men (24.7 +/- 3.4 years; 90.1 +/- 11.3 kg; 176.0 +/- 4.9 cm) ingested supplement (SUPP) or placebo (PL) immediately post-exercise in a randomized, cross-over design. Blood samples were obtained at baseline (BL), immediately (IP), 30-min (30P), 1-h (1H), 2-h (2H), and 5-h (5H) post-exercise to assess plasma concentrations of monocyte chemoattractant protein 1 (MCP-1), myoglobin, cortisol and insulin concentrations; and expressions of C-C chemokine receptor-2 (CCR2), and macrophage-1 antigen (CD11b) on classical monocytes. Magnitude-based inferences were used to provide inferences on the true effects of SUPP compared to PL. Changes in myoglobin, cortisol, and insulin concentrations were similar between treatments. Compared to PL, plasma MCP-1 was "very likely greater" (98.1% likelihood effect) in SUPP at 2H. CCR2 expression was "likely greater" at IP (84.9% likelihood effect), "likely greater" at 1H (87.7% likelihood effect), "very likely greater" at 2H (97.0% likelihood effect), and "likely greater" at 5H (90.1% likelihood effect) in SUPP, compared to PL. Ingestion of SUPP did not influence CD11b expression. Ingestion of an amino acid supplement immediately post-exercise appears to help maintain plasma MCP-1 concentrations and augment CCR2 expression in resistance trained men. PMID- 27384581 TI - Excessive Consumption of Green Tea as a Risk Factor for Periodontal Disease among Korean Adults. AB - This study was performed to assess the relationship between the amount of green tea that is consumed and periodontitis. It is based on data obtained from the Korea National Health and Nutrition Examination Survey, conducted between 2008 and 2010. A community periodontal index equal to code 3 was defined as moderate periodontitis, and code 4 was defined as severe periodontitis (n = 16,726). Consumption of green tea less than one cup per day was associated with a decreased prevalence of periodontal disease among Korean adults. The association between the consumption of green tea and periodontal disease was independent of various potential confounding factors, such as age, sex, body mass index, smoking, drinking, exercise, metabolic syndrome, frequency of tooth brushing per day, use of secondary oral products, the number of dental examination per year, diabetes, hypertension, and white blood cell count. Adjusted odds ratio and 95% confidence interval of no consumption was 1.360 (1.156, 1.601) when participants with consumption of two times per week <= x < 7 times per week was considered as a reference. However, consumption of one or more cups per day increased the prevalence of moderate and severe periodontitis. In conclusion, excessive consumption of green tea may be considered as a risk factor for periodontal disease among Korean adults. PMID- 27384582 TI - Inhibition of Low-Grade Inflammation by Anthocyanins after Microbial Fermentation in Vitro. AB - The anti-inflammatory effects of anthocyanins (ACNs) on vascular functions are discussed controversially because of their low bioavailability. This study was performed to determine whether microorganism (MO)-fermented ACNs influence vascular inflammation in vitro. Therefore, MO growth media were supplemented with an ACN-rich grape/berry extract and growth responses of Escherichia coli, E. faecalis and H. alvei, as well as ACN fermentation were observed. MO supernatants were used for measuring the anti-inflammatory effect of MO-fermented ACNs in an epithelial-endothelial co-culture transwell system. After basolateral enrichment (240 min), endothelial cells were stimulated immediately or after 20 h with TNF alpha. Afterwards, leukocyte adhesion, expression of adhesion molecules and cytokine release were measured. Results indicate that E. coli, E. faecalis and H. alvei utilized ACNs differentially concomitant with different anti-inflammatory effects. Whereas E. coli utilized ACNs completely, no anti-inflammatory effects of fermented ACNs were observed on activated endothelial cells. In contrast, ACN metabolites generated by E. faecalis and H. alvei significantly attenuated low grade stimulated leukocyte adhesion, the expression of adhesion molecules E selectin, VCAM-1 and ICAM-1 and cytokine secretion (IL-8 and IL-6), as well as NF kappaB mRNA expression with a more pronounced effect of E. faecalis than H. alvei. Thus, MO-fermented ACNs have the potential to reduce inflammation. PMID- 27384583 TI - Relationship between the Balance of Hypertrophic/Hyperplastic Adipose Tissue Expansion and the Metabolic Profile in a High Glucocorticoids Model. AB - Adipose tissue (AT) expansion is the result of two processes: hyperplasia and hypertrophy; and both, directly or indirectly, depend on the adipogenic potential of adipocyte precursor cells (APCs). Glucocorticoids (GCs) have a potent stimulatory effect on terminal adipogenesis; while their effects on early stages of adipogenesis are largely unknown. In the present work, we study, in a model of high GC levels, the adipogenic potential of APCs from retroperitoneal AT (RPAT) and its relationship with RPAT mass expansion. We employed a model of hyper adiposity (30- and 60-day-old rats) due to high endogenous GC levels induced by neonatal treatment with l-monosodium glutamate (MSG). We found that the RPAT APCs from 30-day-old MSG rats showed an increased adipogenic capacity, depending on the APCs' competency, but not in their number. Analyses of RPAT adipocyte diameter revealed an increase in cell size, regardless of the rat age, indicating the prevalence of a hypertrophic process. Moreover, functional RPAT alterations worsened in 60-day-old rats, suggesting that the hyperplastic AT expansion found in 30-day-old animals might have a protective role. We conclude that GCs chronic excess affects APCs' adipogenic capacity, modifying their competency. This change would modulate the hyperplastic/hypertrophic balance determining healthy or unhealthy RPAT expansion and, therefore, its functionality. PMID- 27384584 TI - Innovations in Calculating Precise Nutrient Intake of Hospitalized Patients. AB - Obtaining a detailed assessment of a hospitalized patient's nutrient intake is often critically important to ensuring the patient's successful recovery. However, this process is often laborious and prone to error. Inaccurate nutrient intake assessments result in the inability of the healthcare team to recognize patients with developing nutritional deficits that contribute to delayed recovery and prolonged lengths of stay. This paper describes an innovative, easy to use system designed to increase the precision of calorie count reports by using a combination of photography, direct observation, and a specially developed computer program. Although the system was designed specifically for use in a Department of Veterans Affairs Hospital, it has the potential to be adapted for use in other hospital environments. PMID- 27384587 TI - Antioxidant Effect of Extracts from the Coffee Residue in Raw and Cooked Meat. AB - The residue of ground coffee obtained after the brewing process (spent coffee) still contains various functional components with high antioxidant capacity and health benefits, but no attempts have been made to use it as a resource to produce value-added food ingredients. This study evaluates the antioxidant activity of ethanol or hot water extracts from the residues of coffee after brewing. An extraction experiment was carried out using the conventional solid liquid methods, including ethanol and water as the extraction media at different temperatures and liquid/solid ratios. The antioxidant activity of extracts was tested for total phenolic compound (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2-thiobarbituric acid reactive substances (TBARS) using oil emulsion and raw/cooked meat systems. The DPPH radical scavenging activity of the ethanol extracts with heating (HEE) and without heating (CEE) were higher than that of the hot water extracts (WE). The highest DPPH value of HEE and CEE at 1000 ppm was 91.22% and 90.21%, respectively. In oil emulsion and raw/cooked systems, both the water and ethanol extracts had similar antioxidant effects to the positive control (BHA), but HEE and CEE extracts showed stronger antioxidant activities than WE extract. These results indicated that the ethanol extracts of coffee residue have a strong antioxidant activity and have the potential to be used as a natural antioxidant in meat. PMID- 27384586 TI - Activation and Desensitization of Peripheral Muscle and Neuronal Nicotinic Acetylcholine Receptors by Selected, Naturally-Occurring Pyridine Alkaloids. AB - Teratogenic alkaloids can cause developmental defects due to the inhibition of fetal movement that results from desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChRs). We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiperidinyl analog anabaseine, to activate and desensitize peripheral nAChRs expressed in TE 671 and SH-SY5Y cells. Activation-concentration response curves for each alkaloid were obtained in the same multi-well plate. To measure rapid desensitization, cells were first exposed to five potentially-desensitizing concentrations of each alkaloid in log10 molar increments from 10 nM to 100 uM and then to a fixed concentration of acetylcholine (ACh), which alone produces near-maximal activation. The fifty percent desensitization concentration (DC50) was calculated from the alkaloid concentration-ACh response curve. Agonist fast desensitization potency was predicted by the agonist potency measured in the initial response. Anabaseine was a more potent desensitizer than anabasine. Relative to anabaseine, nicotine was more potent to autonomic nAChRs, but less potent to the fetal neuromuscular nAChRs. Our experiments have demonstrated that anabaseine is more effective at desensitizing fetal muscle-type nAChRs than anabasine or nicotine and, thus, it is predicted to be more teratogenic. PMID- 27384588 TI - Non-Response to Antibiotic Treatment in Adolescents for Four Common Infections in UK Primary Care 1991-2012: A Retrospective, Longitudinal Study. AB - We studied non-response rates to antibiotics in the under-reported subgroup of adolescents aged 12 to 17 years old, using standardised criteria representing antibiotic treatment failure. Routine, primary care data from the UK Clinical Practice Research Datalink (CPRD) were used. Annual, non-response rates by antibiotics and by indication were determined. We identified 824,651 monotherapies in 415,468 adolescents: 368,900 (45%) episodes for upper respiratory tract infections (URTIs), 89,558 (11%) for lower respiratory tract infections (LRTIs), 286,969 (35%) for skin/soft tissue infections (SSTIs) and 79,224 (10%) for acute otitis media (AOM). The most frequently prescribed antibiotics were amoxicillin (27%), penicillin-V (24%), erythromycin (11%), flucloxacillin (11%) and oxytetracycline (6%). In 1991, the overall non-response rate was 9.3%: 11.9% for LRTIs, 9.5% for URTIs, 7.1% for SSTIs, 9.7% for AOM. In 2012, the overall non-response rate was 9.2%. Highest non-response rates were for AOM in 1991-1999 and for LRTIs in 2000-2012. Physicians generally prescribed antibiotics to adolescents according to recommendations. Evidence of antibiotic non-response was less common among adolescents during this 22-year study period compared with an all-age population, where the overall non-response rate was 12%. PMID- 27384590 TI - Plasma Surface Modification of Polyhedral Oligomeric Silsequioxane-Poly(carbonate urea) Urethane with Allylamine Enhances the Response and Osteogenic Differentiation of Adipose-Derived Stem Cells. AB - This study present amino functionalization of biocompatible polymer polyhedral oligomeric silsequioxane-poly(carbonate-urea) urethane (POSS-PCU) using plasma polymerization process to induce osteogenic differentiation of adipose derived stem cells (ADSCs). Optimization of plasma polymerization process was carried out keeping cell culture application in mind. Thus, samples were rigorously tested for retention of amino groups under both dry and wet conditions. Physio-chemical characterization was carried out using ninhydrin test, X-ray photon spectroscopy, scanning electron microscopy, and static water contact analysis. Results from physio chemical characterization shows that functionalization of the amino group is not stable under wet conditions and optimization of plasma process is required for stable bonding of amino groups to the POSS-PCU polymer. Optimized samples were later tested in vitro in short and long-term culture to study differentiation of ADSCs on amino modified samples. Short-term cell culture shows that initial cell attachment was significantly (p < 0.001) improved on amine modified samples (NH2-POSS-PCU) compared to unmodified POSS-PCU. NH2-POSS-PCU samples also facilitates osteogenic differentiation of ADSCs as confirmed by immunological staining of cells for extracellular markers such as collagen Type I and osteopontin. Quantification of total collagen and ALP activity also shows significant (p < 0.001) increase on NH2-POSS-PCU samples compared to unmodified POSS-PCU. A pilot study also confirms that these optimized amino modified POSS PCU samples can further be functionalized using bone inducing peptide such as KRSR using conventional wet chemistry. This further provides an opportunity for biofunctionalization of the polymer for various tissue specific applications. PMID- 27384591 TI - Status quo of p53 in the treatment of tumors. AB - The p53 gene is pivotal for oncogenesis in a combination of mutations in oncogenes and antioncogenes. The ubiquitous loss of the p53 pathway in human cancers has generated considerable interest in developing p53-targeted cancer therapies, but current ideas and approaches targeting p53 are conflicting. Current researches focus on cancer-selective drugs with therapeutic strategies that both activate and inhibit p53. As p53 is ubiquitously lost in human cancers, the strategy of exogenous p53 addition is reasonable. However, p53 acts not equally in all cell types; thus, individualized p53 therapy is the direction of future research. To clarify the controversies on p53 for improvement of future antitumor studies, the review focuses on the available technological protocols, including their advantages and limitations in terms of future therapeutic use of p53 in the management of tumors. PMID- 27384585 TI - Ochratoxin A: 50 Years of Research. AB - Since ochratoxin A (OTA) was discovered, it has been ubiquitous as a natural contaminant of moldy food and feed. The multiple toxic effects of OTA are a real threat for human beings and animal health. For example, OTA can cause porcine nephropathy but can also damage poultries. Humans exposed to OTA can develop (notably by inhalation in the development of acute renal failure within 24 h) a range of chronic disorders such as upper urothelial carcinoma. OTA plays the main role in the pathogenesis of some renal diseases including Balkan endemic nephropathy, kidney tumors occurring in certain endemic regions of the Balkan Peninsula, and chronic interstitial nephropathy occurring in Northern African countries and likely in other parts of the world. OTA leads to DNA adduct formation, which is known for its genotoxicity and carcinogenicity. The present article discusses how renal carcinogenicity and nephrotoxicity cause both oxidative stress and direct genotoxicity. Careful analyses of the data show that OTA carcinogenic effects are due to combined direct and indirect mechanisms (e.g., genotoxicity, oxidative stress, epigenetic factors). Altogether this provides strong evidence that OTA carcinogenicity can also occur in humans. PMID- 27384592 TI - The molecular signature of breast cancer metastasis to bone. AB - Distant metastasis during the advanced stage of malignant tumor progression can cause considerable morbidity in cancer patients. Bone is known to be one of the most common sites of distant metastasis in patients with breast cancer (BC). BC metastases in bone are associated with excessive skeletal complications. These complications can be fatal and reduce quality of life of patients. It is important to understand the metastatic process of BC to bone to improve quality of life and design new therapeutic methods. At present, the molecular mechanisms leading to the BC metastasis to bone are not fully understood. Studying the molecular basis of BC metastasis to bone might improve our insight into this complex process. In addition, it can provide novel approaches for designing advanced and effective targeted therapies. The present article aimed to review the published papers on the molecular basis of the metastatic process of BC to bone, focusing on involved genes and signaling networks. Furthermore, we propose potential therapeutic targets that may be more effective for the inhibition and treatment of BC metastasis to bone. PMID- 27384589 TI - Turning on the Radio: Epigenetic Inhibitors as Potential Radiopriming Agents. AB - First introduced during the late 1800s, radiation therapy is fundamental to the treatment of cancer. In developed countries, approximately 60% of all patients receive radiation therapy (also known as the sixty percenters), which makes radioresistance in cancer an important and, to date, unsolved, clinical problem. Unfortunately, the therapeutic refractoriness of solid tumors is the rule not the exception, and the ubiquity of resistance also extends to standard chemotherapy, molecularly targeted therapy and immunotherapy. Based on extrapolation from recent clinical inroads with epigenetic agents to prime refractory tumors for maximum sensitivity to concurrent or subsequent therapies, the radioresistant phenotype is potentially reversible, since aberrant epigenetic mechanisms are critical contributors to the evolution of resistant subpopulations of malignant cells. Within the framework of a syllogism, this review explores the emerging link between epigenetics and the development of radioresistance and makes the case that a strategy of pre- or co-treatment with epigenetic agents has the potential to, not only derepress inappropriately silenced genes, but also increase reactive oxygen species production, resulting in the restoration of radiosensitivity. PMID- 27384593 TI - Next-generation sequencing in patients with advanced cancer: are we ready for widespread clinical use? A single institute's experience. AB - The next-generation sequencing (NGS) assay targeting cancer-relevant genes has been adopted widely for use in patients with advanced cancer. The primary aim of this study was to assess the clinical utility of commercially available NGS. We retrospectively collected demographic and clinicopathologic data, recommended therapy, and clinical outcomes of 30 patients with a variety of advanced solid tumors referred to Foundation Medicine NGS. The initial pathologic examination was performed at the pathology department of the referring hospital. The comprehensive clinical NSG assay was performed on paraffin-embedded tumor samples using the Clinical Laboratory Improvement Amendments-certified FoundationOne platform. The median number of genomic alterations was 3 (0-19). The median number of therapies with potential benefit was 2 (0-8). In 12 cases, a comprehensive clinical NGS assay did not indicate any therapy with potential benefit according to the genomic profile. Ten of the 30 patients received treatments recommended by genomic profile results. In six of the 10 cases, disease progressed within 2 months and four patients died within 3 months of treatment initiation. Three of the 30 patients benefited from a comprehensive clinical NGS assay and the subsequent recommended therapy. The median PFS was 12 weeks (95% confidence interval 10-57) in patients treated with molecularly targeted agents chosen on the basis of tumor genomic profiling versus 48 weeks (95% confidence interval 8-38) in the control group treated with physician choice therapy (P=0.12). Our study suggests that NGS can detect additional treatment targets in individual patients, but prospective medical research and appropriate clinical guidelines for proper clinical use are vital. PMID- 27384594 TI - Surrogate Imaging Biomarkers of Response of Colorectal Liver Metastases After Salvage Radioembolization Using 90Y-Loaded Resin Microspheres. AB - OBJECTIVE: The purpose of the present study is to evaluate Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, tumor attenuation criteria, Choi criteria, and European Organization for Research and Treatment of Cancer (EORTC) PET criteria as measures of response and subsequent predictors of liver progression-free survival (PFS) after radioembolization (RE) of colorectal liver metastases (CLM). The study also assesses interobserver variability for measuring tumor attenuation using a single 2D ROI on a simple PACS workstation. MATERIALS AND METHODS: We performed a retrospective review of the clinical RE database at our institution, to identify patients treated in the salvage setting for CLM between December 2009 and March 2013. Response was evaluated on FDG PET scans, with the use of EORTC PET criteria, and on portal venous phase CT scans, with the use of RECIST 1.1, tumor attenuation criteria, and Choi criteria. Two independent blinded observers measured tumor attenuation using a single 2D ROI. The intraclass correlation coefficient (ICC) for interobserver variability was assessed. Kaplan-Meier methodology was used to calculate liver PFS, and the log rank test was used to assess the response criteria as predictors of liver PFS. RESULTS: A total of 25 patients with 46 target tumors were enrolled in the study. The ICC was 0.95 at baseline and 0.98 at response evaluation. Among the 25 patients, more responders (i.e., partial response) were identified on the basis of EORTC PET criteria (n = 14), Choi criteria (n = 15), and tumor attenuation criteria (n = 13) than on the basis of RECIST 1.1 (n = 2). The median liver PFS was 3.0 months (95% CI, 2.1-4.0 months). Response identified on the basis of EORTC PET criteria (p < 0.001), Choi criteria (p < 0.001), or tumor attenuation criteria (p = 0.01) predicted liver PFS; however, response identified by RECIST 1.1 did not (p = 0.1). CONCLUSION: RECIST 1.1 has poor sensitivity for detecting metabolic responses classified by EORTC PET criteria. EORTC PET criteria, Choi criteria, and tumor attenuation criteria appear to be equally reliable surrogate imaging biomarkers of liver PFS after RE in patients with CLM. PMID- 27384595 TI - Current Advancement in Multidisciplinary Treatment for Resectable cStage II/III Esophageal Squamous Cell Carcinoma in Japan. AB - Multidisciplinary treatment comprising surgery, chemotherapy, and radiotherapy for resectable esophageal squamous cell carcinoma (ESCC) is widely used with improved prognosis. Transthoracic esophagectomy (TTE) with extended lymph node (LN) dissection, known as three field LN dissection, has been recommended for ESCC using open thoracotomy or the thoracoscopic approach. The Japan Clinical Oncology Group (JCOG) trial (JCOG1409) is investigating the patients' long term survival using the thoracoscopic approach that has been shown to reduce the incidence of postoperative respiratory complication. For perioperative treatment, neoadjuvant chemotherapy using cisplatin plus 5-fluorouracil (5-FU), has been accepted as the standard of care in Japan based on the JCOG9907 trial. In Western countries, neoadjuvant chemoradiotherapy was shown to prolong overall survival for esophageal cancer, including ESCC. Although surgery has been recognized as an initial curative treatment for esophageal cancer, definitive chemoradiotherapy is an alternative treatment for patients who are unable to undergo thoracotomy or who decline to undergo surgery. This article reviews multidisciplinary treatment advances for ESCC. However, current standard treatments are country dependent and the ongoing trial may help standardize ESCC treatment across various societies. PMID- 27384596 TI - Therapeutic efficacy and effects of artesunate-amodiaquine and artemether lumefantrine on malaria-associated anaemia in Nigerian children aged two years and under. AB - BACKGROUND: Artemisinin-based combination therapies are recommended as first-line treatments for uncomplicated falciparum malaria, but there is little evaluation of their efficacy and effects on uncomplicated malaria-associated anaemia in children aged 2 years and under. METHODS: Parasitological efficacy and effects on malaria-associated anaemia were evaluated in 250 malarious children aged 2 years and under, and efficacy was evaluated in 603 malarious children older than two but younger than 5 years of age following treatment with artesunate-amodiaquine (AA) or artemether-lumefantrine (AL). Kinetics of the disposition of parasitaemia following treatment were evaluated using a non-compartment model. Late-appearing anaemia (LAA) was diagnosed using the following criteria: clearance of parasitaemia, fever and other symptoms occurring within 7 days of starting treatment, adequate clinical and parasitological response on days 28-42, haematocrit (HCT) >= 30 % at 1 and/or 2 weeks, a fall in HCT to < 30 % occurring at 3-6 weeks, absence of concomitant illness at 1-6 weeks, and absence of asexual parasitaemia detected using both microscopy and polymerase chain reaction (PCR) at 1-6 weeks. RESULTS: Overall, in children aged 2 years and under, the PCR corrected parasitological efficacy was 97.2 % (95 % CI 92.8-101.6), which was similar for both treatments. In children older than 2 years, parasitological efficacy was also similar for both treatments, but parasite prevalence 1 day after treatment began was significantly higher, and fever and parasite clearance times were significantly faster in the AA-treated children compared with the AL treated children. Declines in parasitaemia were monoexponential with an estimated elimination half-time of 1 h. Elimination half-times were similar for both treatments. In children aged 2 years and under who were anaemic at presentation, the mean anaemia recovery time was 12.1 days (95 % CI 10.6-13.6, n = 127), which was similar for both treatments. Relatively asymptomatic LAA occurred in 11 children (4.4 %) aged 2 years and under, the recovery from which was uneventful. CONCLUSION: This study showed that AA and AL are efficacious treatments for uncomplicated falciparum malaria in Nigerian children aged 2 years and under, and that AA clears parasitaemia and fever significantly faster than AL in children older than 2 years. Both treatments may cause a relatively asymptomatic LAA with uneventful recovery in a small proportion of children aged 2 years and under. TRIALS REGISTRATION: Pan African Clinical Trial Registry PACTR201508001188143, 3 July 2015; PACTR201510001189370, 3 July 2015; PACTR201508001191898, 7 July 2015 and PACTR201508001193368, 8 July 2015 http://www.pactr.org . PMID- 27384597 TI - Helical-Peptide-Catalyzed Enantioselective Michael Addition Reactions and Their Mechanistic Insights. AB - Helical peptide foldamer catalyzed Michael addition reactions of nitroalkane or dialkyl malonate to alpha,beta-unsaturated ketones are reported along with the mechanistic considerations of the enantio-induction. A wide variety of alpha,beta unsaturated ketones, including beta-aryl, beta-alkyl enones, and cyclic enones, were found to be catalyzed by the helical peptide to give Michael adducts with high enantioselectivities (up to 99%). On the basis of X-ray crystallographic analysis and depsipeptide study, the amide protons, N(2)-H and N(3)-H, at the N terminus in the alpha-helical peptide catalyst were crucial for activating Michael donors, while the N-terminal primary amine activated Michael acceptors through the formation of iminium ion intermediates. PMID- 27384598 TI - [Presentation]. PMID- 27384599 TI - [Antithrombotic therapy in patients undergoing transcatheter aortic valve implantation]. AB - Transcatheter aortic valve implantation (TAVI) has emerged as a valid alternative to surgical replacement in patients with severe aortic stenosis. Bleeding and cerebral ischemic events remain frequent complications of this procedure during the periprocedural period and at follow-up with a severe impact on survival. Therefore, there is growing interest towards the optimal antithrombotic therapy to manage patients undergoing TAVI. International guidelines support the adoption of a dual antiplatelet therapy after TAVI, although there is heterogeneity in the suggested duration and the concomitant association with an oral anticoagulant in patients with specific indications, mainly those with atrial fibrillation. Recent data have questioned the benefits of adding clopidogrel to aspirin, showing a slight increase in bleeding compared with aspirin therapy alone. Importantly, recent studies have also underlined the risks of valve thrombosis and the potential benefits of oral anticoagulant therapy in patients undergoing TAVI. Currently, large randomized trials are ongoing and are expected to provide relevant information to guide recommendations on the most appropriate antithrombotic therapy in these patients. Tailored therapy based on the patient's risk profile remains relevant in daily clinical practice. PMID- 27384600 TI - [Antithrombotic therapy in patients undergoing transcatheter aortic valve implantation: the quest for the Holy Grail]. PMID- 27384602 TI - [The "Renaissance" of interventional cardiology]. PMID- 27384601 TI - [Current practice and changing trends in the percutaneous treatment of structural heart disease. Results of a multicenter survey promoted by the Italian Society of Interventional Cardiology in six Italian Regions including Tuscany, Lombardy, Veneto, Emilia-Romagna, Campania and Puglia]. AB - BACKGROUND: Significant developments have occurred in the field of percutaneous interventions for structural heart disease over the last decade. The introduction of several innovations has expanded significantly the spectrum of therapeutic applications of structural interventional cardiology. However, the translation of the most recent scientific evidence into clinical practice and the adoption of new technologies may be susceptible to large variability, even within the same geographic area. This study aimed at describing current status and changing trends of structural heart interventions within 6 Regions in Italy. METHODS: Between July 2015 and October 2015, 6 regional delegations of the Italian Society of Interventional Cardiology (SICI-GISE) promoted a web-based multicenter survey concerning structural heart interventions. An ad hoc questionnaire was administered to head physicians of the cath-labs of 4 Regions of Northern Italy (Tuscany, Lombardy, Veneto and Emilia-Romagna) and 2 Regions of Southern Italy (Puglia and Campania). Also, in this study we considered previous data from a similar survey that involved Tuscany, Lombardy, Veneto and Emilia-Romagna between April 2014 and May 2014. Data from the two surveys were compared, observing the changing trends between 2014 and 2015. RESULTS: The 2015 survey was completed in more than two thirds (68%) of the 145 eligible cath-labs. According to the survey, the application of percutaneous structural heart interventions and the availability of devices were wide and homogeneous within the 6 Regions involved. The main factors perceived as limiting the execution of structural heart interventions resulted economic (e.g. cost of procedures and devices) or organizational (e.g. limited diffusion of hybrid operating rooms). CONCLUSIONS: In this study, which was based on the results of a recent survey conducted in 6 Italian Regions, structural heart interventions resulted widely growing throughout the investigated area. The indications for treatment and the availability of devices were relatively homogeneous between the regions involved, as well as the limiting factors, which appear to be mainly economic organizational. PMID- 27384603 TI - [ST-segment elevation myocardial infarction in a patient with thrombophilia taking new oral anticoagulants]. AB - We report the case of a 65--year-old woman admitted for inferior ST-segment elevation myocardial infarction complicated by complete atrioventricular block. The patient was under treatment with a novel oral anticoagulant (NOAC, rivaroxaban) because of a history of recurrent idiopathic pulmonary embolism. Emergency angiography showed complete acute thrombotic occlusion of the right coronary artery. After manual thrombectomy, there was no angiographic evidence of underlying atherosclerosis, therefore no further percutaneous coronary intervention was performed. Subsequent clinical course was uneventful. Laboratory tests demonstrated the presence of a heterozygous mutation of the factor II gene (G20210A), confirming the clinical evidence of a thrombophilic state. As rivaroxaban seemed to be ineffective in preventing spontaneous coronary thrombosis in this patient, antithrombotic therapy was shifted to warfarin plus low-dose aspirin. No further ischemic events occurred during the 1-year follow up. It can be hypothesized that factor Xa inhibition by NOACs, such as rivaroxaban, could be insufficient in case of a thrombophilic state due to thrombin mutation. A brief review of the current literature on use of NOACs in acute coronary syndromes is also reported. PMID- 27384604 TI - Starting over: Primpol reprimes after chain termination. PMID- 27384605 TI - Effect of fermentation and sterilization on anthocyanins in blueberry. AB - BACKGROUND: Blueberry products have various health benefits due to their high content of dietary anthocyanins. The aim of this study was to investigate the impact of fermentation and sterilization on total anthocyanin content, composition and some quality attributes of blueberry puree. The blueberry puree used here was fermented for 40 h at 37 degrees C by Lactobacillus after sterilization. The method of ultra-performance liquid chromatography-mass spectrometry was optimized for the rapid analysis of anthocyanins. Quality attributes including pH, color, total soluble solids and viscosity were measured. RESULTS: A total of 21 anthocyanins and five anthocyanidins were quantified by ultra-performance liquid chromatography. Fermented blueberry had reduced total anthocyanin content (29%) and levels of individual anthocyanins compared with fresh blueberry. Total anthocyanin content was decreased 46% by sterilization, and different degradation behavior of individual anthocyanin was appeared between fermented and sterilized-fermented blueberry puree. Fermentation and sterilization decreased the total soluble solids and pH and changed color parameters, while minimally influencing viscosity. CONCLUSIONS: The loss of total anthocyanin content by fermentation was related to the unstable structure of blueberry anthocyanins. Anthocyanins are sensitive to temperature (>80 degrees C), and degradation of anthocyanins by sterilization in blueberry should be considered in the fermentation procedure. (c) 2016 Society of Chemical Industry. PMID- 27384606 TI - N-3 vs. n-6 fatty acids differentially influence calcium signalling and adhesion of inflammatory activated monocytes: impact of lipid rafts. AB - BACKGROUND: Anti-inflammatory n-3 fatty acids (FA) like docosahexaenoic acid (DHA) opposed to the pro-inflammatory n-6 FA arachidonic acid (AA) might modulate lipid rafts within the cell membrane by differential incorporation. In inflammation, monocyte adhesion to endothelial cells is a crucial step mediated by intracellular calcium changes. We investigated whether lipid rafts mediate FA induced modulation of adhesion and intracellular calcium. METHODS: In isolated human monocytes and monocytic U937 cells we measured adhesion to human umbilical vein endothelial cells (HUVEC) using a parallel flow chamber and a static assay, adhesion molecules by FACScan, and intracellular calcium by fluorescence. Monocyte lipid rafts were isolated by ultracentrifugation and submitted to gas chromatography for FA analysis. RESULTS: Pre-incubation with AA or DHA resulted in a predominant incorporation of the respective FA into raft compared to non raft fraction. DHA as compared to AA significantly reduced monocyte adhesion and calcium release after stimulation with TNF-alpha while expression of adhesion molecules remained unchanged. Pre-treatment with a calcium chelator abolished the effect of FA on calcium and adhesion. Disruption of lipid rafts prevented FA induced modulations. CONCLUSION: Incorporation of FA into lipid rafts seem to be crucial for modulation of adhesion under inflammatory conditions. PMID- 27384608 TI - Transmission imaging for integrated PET-MR systems. AB - Attenuation correction for PET-MR systems continues to be a challenging problem, particularly for body regions outside the head. The simultaneous acquisition of transmission scan based MU-maps and MR images on integrated PET-MR systems may significantly increase the performance of and offer validation for new MR-based MU-map algorithms. For the Biograph mMR (Siemens Healthcare), however, use of conventional transmission schemes is not practical as the patient table and relatively small diameter scanner bore significantly restrict radioactive source motion and limit source placement. We propose a method for emission-free coincidence transmission imaging on the Biograph mMR. The intended application is not for routine subject imaging, but rather to improve and validate MR-based MU map algorithms; particularly for patient implant and scanner hardware attenuation correction. In this study we optimized source geometry and assessed the method's performance with Monte Carlo simulations and phantom scans. We utilized a Bayesian reconstruction algorithm, which directly generates MU-map estimates from multiple bed positions, combined with a robust scatter correction method. For simulations with a pelvis phantom a single torus produced peak noise equivalent count rates (34.8 kcps) dramatically larger than a full axial length ring (11.32 kcps) and conventional rotating source configurations. Bias in reconstructed MU maps for head and pelvis simulations was ?4% for soft tissue and ?11% for bone ROIs. An implementation of the single torus source was filled with (18)F fluorodeoxyglucose and the proposed method quantified for several test cases alone or in comparison with CT-derived MU-maps. A volume average of 0.095 cm(-1) was recorded for an experimental uniform cylinder phantom scan, while a bias of <2% was measured for the cortical bone equivalent insert of the multi-compartment phantom. Single torus MU-maps of a hip implant phantom showed significantly less artifacts and improved dynamic range, and differed greatly for highly attenuating materials in the case of the patient table, compared to CT results. Use of a fixed torus geometry, in combination with translation of the patient table to perform complete tomographic sampling, generated highly quantitative measured MU maps and is expected to produce images with significantly higher SNR than competing fixed geometries at matched total acquisition time. PMID- 27384607 TI - The modulation of Th2 immune pathway in the immunosuppressive effect of human umbilical cord mesenchymal stem cells in a murine asthmatic model. AB - BACKGROUND: Asthma is a chronic airway inflammatory disease that has a high prevalence nowadays, and seeking the means of relieving asthmatic symptoms is now an issue with increased importance. While mesenchymal stem cells have been demonstrated to display immunomodulatory effects, the effect of fetus-type mesenchymal stem cells (MSCs) on asthmatic symptoms in vivo have not been reported to date. METHODS: Female BALB/c mice at 8 weeks of age were sensitized by ovalbumin, and MSCs derived from Wharton's jelly of human umbilical cord mesenchymal stem cells (hUCMSCs) were injected into the asthmatic mice. Airway hyper-responsiveness, lung eosinophil infiltration, cytokine level in splenocyte cultures and serum immunoglobulin level were measured. Enzyme-linked immunosorbent assay was used to determine cytokine and immunoglobulin levels. RESULTS: This current study demonstrated that hUCMSCs attenuated both lung lymphocyte and eosinophil infiltration, and significantly decreased the concentration of Th2 cytokines interleukin-5 in splenocyte cultures. CONCLUSIONS: Human umbilical cord mesenchymal stem cells have the advantage of being easily harvested non-invasively and are capable of rapid proliferation, therefore an ideal material for stem cell-based immune therapies. The current study showed that fetal-type MSCs were able to suppress asthmatic symptoms efficiently, and its immunomodulatory effect resulted primarily from suppressing the Th2 pathway in the animal model. This study suggested that hUCMSCs could be an ideal candidate for cell-based therapies of asthma. PMID- 27384610 TI - Communicating With Dying Patients and Their Families: Multimedia Training in End of-Life Care. AB - BACKGROUND: The need for end-of-life (EOL), high-impact education initiatives to prepare medical students to communicate with dying patients and their families and to cope with issues of death and dying, is well recognized. METHODS: Third year medical students (n = 224), during their ambulatory rotation, completed a multimedia EOL curriculum, which included pre-/posttests, an online case-based module, didactic presentation, and a tablet computer application designed to demonstrate the signs and symptoms seen in the last hours of life for families of dying patients. Pre- and posttests were compared using Pearson chi2 or Fisher exact test, and improvement was measured by weighted kappa coefficient. RESULTS: On preintervention surveys, the majority of students demonstrated positive attitudes toward the care of dying patients and their families. Despite this high pretest positive attitude, there was a statistically significant overall positive attitude change after the intervention. The lowest pretest positive attitudes and lowest posttest positive attitude shifts, although all statistically improved, involved addressing the thoughts and feelings of dying patients and in coping with their own emotional response. CONCLUSIONS: Medical students exposure to this multimedia EOL curriculum increases positive attitudes in caring for dying patients and their families. PMID- 27384609 TI - Diagnostic reference levels and complexity indices in interventional radiology: a national programme. AB - OBJECTIVES: To propose national diagnostic reference levels (DRLs) for interventional radiology and to evaluate the impact of the procedural complexity on patient doses. METHODS: Eight interventional radiology units from Spanish hospitals were involved in this project. The participants agreed to undergo common quality control procedures for X-ray systems. Kerma area product (KAP) was collected from a sample of 1,649 procedures. A consensus document established the criteria to evaluate the complexity of seven types of procedures. DRLs were set as the 3rd quartile of KAP values. RESULTS: The KAP (3rd quartile) in Gy cm2 for the procedures included in the survey were: lower extremity arteriography (n = 784) 78; renal arteriography (n = 37) 107; transjugular hepatic biopsies (THB) (n = 30) 45; biliary drainage (BD) (n = 314) 30; uterine fibroid embolization (UFE) (n = 56) 214; colon endoprostheses (CE) (n = 31) 169; hepatic chemoembolization (HC) (n = 269) 303; femoropopliteal revascularization (FR) (n = 62) 119; and iliac stent (n = 66) 170. The complexity involved the increases in the following KAP factors from simple to complex procedures: THB x4; BD x13; UFE x3; CE x3; HC x5; FR x5 and IS x4. CONCLUSIONS: The evaluation of the procedure complexity in patient doses will allow the proper use of DRLs for the optimization of interventional radiology. KEY POINTS: * National DRLs for interventional procedures have been proposed given level of complexity * For clinical audits, the level of complexity should be taken into account. * An evaluation of the complexity levels of the procedure should be made. PMID- 27384611 TI - Rationale and design of the PREFERS (Preserved and Reduced Ejection Fraction Epidemiological Regional Study) Stockholm heart failure study: an epidemiological regional study in Stockholm county of 2.1 million inhabitants. AB - AIMS: Heart failure (HF) with preserved (HFpEF) or reduced (HFrEF) ejection fraction is associated with poor prognosis and quality of life. While the incidence of HFrEF is declining and HF treatment is effective, HFpEF is increasing, with no established therapy. PREFERS Stockholm is an epidemiological study with the aim of improving clinical care and research in HF and to find new targets for drug treatment in HFpEF (https://internwebben.ki.se/sites/default/files/20150605_4d_research_appendix_fin l.pdf). METHODS: Patients with new-onset HF (n = 2000) will be characterized at baseline and after 1-year follow-up by standardized protocols for clinical evaluation, echocardiography, and ECG. In one subset undergoing elective coronary bypass surgery (n = 100) and classified according to LV function, myocardial biopsies will be collected during surgery, and cardiac magnetic resonance (CMR) imaging will be performed at baseline and after 1 year. Blood and tissue samples will be stored in a biobank. We will characterize and compare new-onset HFpEF and HFrEF patients regarding clinical findings and cardiac imaging, genomics, proteomics, and transcriptomics from blood and cardiac biopsies, and by established biomarkers of fibrosis, inflammation, haemodynamics, haemostasis, and thrombosis. The data will be explored by state-of-the-art bioinformatics methods to investigate gene expression patterns, sequence variation, DNA methylation, and post-translational modifications, and using systems biology approaches including pathway and network analysis. CONCLUSIONS: In this epidemiological HF study with biopsy studies in a subset of patients, we aim to identify new biomarkers of disease progression and to find pathophysiological mechanisms to support explorations of new treatment regimens for HFpEF. PMID- 27384612 TI - Dyadic Configurations of Sexual Problems Among Older U.S. Adults: A National Study. AB - Using data from the 2010-2011 National Social Life Health and Aging Project (NSHAP)-a nationally representative probability sample of older U.S. adults as well as their partners-this study provides the first comprehensive, population based analysis of dyadic configurations of sexual problems and their correlates among those aged 60 to 90 years. Results suggest the majority of late-life partnerships (N = 854) may not have a heavy burden of sexual difficulties. However, almost a fifth (18.21%) of partnered older women do not abstain from sex despite low sexual motivation and capacity. This relational "type" seems unlinked to demographic or health attributes, and may be driven more by partnership strains. In addition, an "at risk" group with consistent sexual problems, arguably due to age-related decline, comprises 27.16% of all late-life couples. PMID- 27384613 TI - PDMS microwells for multi-parametric monitoring of single mitochondria on a large scale: a study of their individual membrane potential and endogenous NADH. AB - Microwell arrays have been developed to monitor simultaneously, and on a large scale, multiple metabolic responses of single mitochondria. Wells of 50 to 1000 MUm-diameter were prepared based on easy structuration of thin polydimethylsiloxane layers (PDMS; 100 MUm thickness). Their surface treatment with oxygen plasma allowed the immobilization in situ and observation with time of populations of single isolated mitochondria. Their metabolic activities could be monitored individually by fluorescence microscopy under several activation/inhibition conditions. We measured the concomitant variations of two main metabolic parameters - the endogenous NADH level and the internal membrane potential difference Deltapsi owing to a cationic fluorescent probe (TMRM) - at energized, uncoupled and inhibited stages of the mitochondrial respiratory chain. Microwell arrays allowed analyses on large populations, and consequently statistical studies with a single organelle resolution. Thus, we observed rapid individual polarizations and depolarizations of mitochondria following their supply with the energetic substrate, while an averaged global polarization (increase of TMRM fluorescence within mitochondria) and NADH increase were detected for the whole population. In addition, statistical correlation studies show that the NADH content of all mitochondria tends toward a metabolic limit and that their polarization-depolarization ability is ubiquitous. These results demonstrate that PDMS microwell platforms provide an innovative approach to better characterize the individual metabolic status of isolated mitochondria, possibly as a function of their cell or organ origin or in different physio pathological situations. PMID- 27384614 TI - Association between microRNAs and coronary collateral circulation: is there a new role for the small non-coding RNAs? AB - We read with interest the article entitled "Circulating microRNAs characterizing patients with insufficient coronary collateral artery function" which was recently published in the PLOS ONE journal. It was demonstrated for the first time that specific circulating microRNAs (miRNAs) can distinguish patients with sufficient from those with insufficient coronary collateral circulation. Circulating miRNAs in the plasma of patients with stable CAD and chronic CTO could provide information with regard to the coronary collateral artery capacity. However, several aspects need to be taken into consideration before the use of miRNAs in the clinical practice. A risk model that would incorporate risk factors for cardiovascular disease and miRNAs could prove to be very useful. Although an association between the levels of miRNAs and the collateral artery capacity appears promising, it still does not confirm any causal role for miRNAs. Therefore, large clinical studies in populations with CTO are warranted to evaluate this finding. PMID- 27384615 TI - Preservation of overmature, ancient, sedimentary organic matter in carbonate concretions during outcrop weathering. AB - Concretions are preferentially cemented zones within sediments and sedimentary rocks. Cementation can result from relatively early diagenetic processes that include degradation of sedimentary organic compounds or methane as indicated by significantly 13 C-depleted or enriched carbon isotope compositions. As minerals fill pore space, reduced permeability may promote preservation of sediment components from degradation during subsequent diagenesis, burial heating and outcrop weathering. Discrete and macroscopic organic remains, macro and microfossils, magnetic grains, and sedimentary structures can be preferentially preserved within concretions. Here, Cretaceous carbonate concretions of the Holz Shale are shown to contain relatively high carbonate-free total organic carbon (TOC) contents (up to ~18.5 wt%) compared to the surrounding host rock (with <2.1 wt%). TOC increases with total inorganic carbon (TIC) content, a metric of the degree of cementation. Pyrite contents within concretions generally correlate with organic carbon contents. Concretion carbonate carbon isotope compositions (delta13 Ccarb ) range from -22.5 to -3.40/00 (VPDB) and do not correlate strongly with TOC. Organic carbon isotope compositions (delta13 Corg ) of concretions and host rock are similar. Thermal maturity data indicate that both host and concretion organic matter are overmature and have evolved beyond the oil window maturity stage. Although the organic matter in general has experienced significant oxidative weathering, concretion interiors exhibit lower oxygen indices relative to the host. These results suggest that carbonate concretions can preferentially preserve overmature, ancient, sedimentary organic matter during outcrop weathering, despite evidence for organic matter degradation genetic mechanisms. As a result, concretions may provide an optimal proxy target for characterization of more primary organic carbon concentrations and chemical compositions. In addition, these findings indicate that concretions can promote delayed oxidative weathering of organic carbon in outcrop and therefore impact local chemical cycling. PMID- 27384616 TI - [Climate change and health]. PMID- 27384617 TI - [The Peruvian Journal of Experimental Medicine and Public Health continues to serve the public health of Peru and Latin America]. PMID- 27384618 TI - [Factors behind people's reluctance towards dengue vector control actions in three districts in northern Peru]. AB - OBJECTIVES: To identify factors behind a community's reluctance to dengue vector control efforts in three districts of the Piura region in Peru. MATERIALS AND METHODS: Fieldwork was conducted in May 2015 in the districts of Mori, Rinconada, Llicuar, and Sullana on the northern coast of Peru. Qualitative research methods were employed to understand varying perspectives of individuals involved in the dengue issue. Techniques such as interviewing and observation were used. Interviews included open-ended, in-depth questions. Individual interviews, focus groups, and home visits of community members were performed. RESULTS: Reluctance was based on four arguments: 1. Fumigation is ineffective; 2. Personnel intervening are untrustworthy; 3. The timing of activities is unsuitable; and 4. The larvicide used affected water quality and taste. There was clear heterogeneity in reluctant groups: community members with high economic status, residents in high-risk or "red zone" areas, families with someone working as a healthcare professional, and houses with an ill or disabled member. CONCLUSIONS: The arguments behind reluctance as well as the composition of groups reluctant to vector control during dengue outbreaks in the districts examined were heterogeneous. Control strategies must take this heterogeneity into account. PMID- 27384619 TI - [Quali-quantitative study on healthcare for children below the age of 3 at health establishments in nine underdeveloped regions of Peru]. AB - OBJECTIVES: To assess five elements of healthcare quality (physical space, equipment, personnel, waiting time, and counseling) in growth and development services (GDS) at 18 healthcare establishments in nine regions of Peru with high rates of poverty. MATERIALS AND METHODS: A quali-quantitative study was carried out in the Amazonas, Apurimac, Ayacucho, Cajamarca, Cusco, Huanuco, Huancavelica, Puno, and Ucayali regions, that included direct observation (DO) during medical assistance in GDS, focus groups (FG, one user per healthcare establishment), and in-depth interviews (IDI) with healthcare workers (two per healthcare establishment). RESULTS: There were 18 DOs carried out to assess environment and equipment, 23 DOs of complete service shifts, 67 accompaniments to users during medical assistance in GDS, 18 FGs (118 participating mothers), and 36 IDIs. Both mothers and healthcare professionals agreed that there were limitations in infrastructure, equipment, materials, and personnel that impacted quality medical assistance in GDS. Delays in medical assistance, failure to comply with schedules, and lack of friendliness when providing medical care were the aspects that produced the greatest user dissatisfaction. Only 24.3% of the total amount of time spent at the healthcare establishment corresponded to beneficial activities for the user, although the Health Department was meeting the objective to promote improvement of childcare practices. CONCLUSIONS: The study was useful in identifying weaknesses and strengths that may help redirect GDS efforts within the framework of policies aimed at strengthening first-class medical assistance. PMID- 27384620 TI - [Antimicrobial resistance of Salmonella spp isolated animal food for human consumption]. AB - OBJECTIVES: To analyze all information available on antimicrobial-resistant Salmonella species isolated from foods of animal origin that are used for human consumption in Latin America. MATERIALS AND METHODS: A systematic review of observational epidemiological studies conducted in Latin America between 2003 and 2014 was carried out using the PubMed and LILACS databases. Studies conducted as part of analyses of outbreaks or cases of human infection were not included. Three reviewers independently participated in the study selection. Additionally, the studies included underwent quality assessment. RESULTS: A total of 25 studies met the inclusion criteria. The studies included were conducted in Brazil, Mexico, Colombia, Argentina, and Venezuela. Salmonella spp. isolates were obtained mainly from animal-based foods derived from cattle, swine, and poultry, revealing that Salmonella typhimurium and S. enteritidis were the most frequently isolated serotypes (17 and 11 studies, respectively). In 23 studies, Salmonella spp. showed resistance to more than one antibiotic, including nalidixic acid, streptomycin, tetracycline, chloramphenicol, ampicillin, trimethoprim sulfamethoxazole, gentamicin, ciprofloxacin, and cephalosporins. CONCLUSIONS: Salmonella spp. isolates obtained mainly from animal-based foods for human consumption in the countries analyzed often show resistance to several antibiotics. It is important that more countries in Latin America carry out and publish studies on Salmonella spp. resistance in order to establish and monitor adequate control strategies. PMID- 27384621 TI - [GHRd3 polymorphism of growth hormone receptor gen in peruvian children with idiopathic short stature]. AB - OBJECTIVES: To describe the standardization of molecular detection and frequency of a growth hormone receptor gene deleted for exon three (GHRd3) polymorphism in a population of Peruvian children with idiopathic short stature. MATERIALS AND METHODS: Peripheral blood samples were used from patients (N=64) who were diagnosed with idiopathic short stature and were treated at the endocrinology unit of the National Institute of Child Health in Peru The amplification of exon 3 was carried out using G1, G2, and G3 primers by optimizing PCR conditions, such as annealing temperature and magnesium concentration. RESULTS: The specificity of primers was maximized at 67 degrees C and there were no differences between magnesium concentration tests. Two-thirds (67%) of patients were GHRfl homozygous, 28% were heterozygous, and 5% were GHRd3 homozygous. CONCLUSIONS: The test was useful in determining the genotypes of patients with idiopathic short stature and revealed that only 5% had a genotype that would respond better to rhGH treatment. Thus, molecular assays may be useful when considering the decision to start drug therapy. PMID- 27384622 TI - [Comparison of prognostic scoring systems in the prediction of mortality and complications from sepsis]. AB - OBJECTIVES: To compare the Mortality in Emergency Department Sepsis (MEDS), Sepsis-related Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation (APACHE II), and Confusion, Urea, Respiratory rate, Blood pressure, 65 years of age and older (CURB-65) scoring systems for predicting mortality and complications in septic patients. MATERIALS AND METHODS: A prospective study of diagnostic test assessment was carried out. Scores were compared by analysis of receiver operating characteristic (ROC) curves corresponding to each score, with the development of death or complications as the dependent variable. RESULTS: There were 265 patients included in the analysis; 155 (58.4%) patients died and/or presented complications. The multivariate analysis revealed variables associated with mortality and complications were age, oliguria, mental health impairment, acute lung injury, and the use of inotropes. Analysis of ROC curves showed the area below the ROC curve was 0.74 (95% CI: 0.68-0.80) for SOFA, 0.73 (95% CI: 0.67-0.79) for MEDS, 0.73 (95% CI: 0.66-0.79) for APACHE II, and 0.67 (95% CI: 0.60-0.73) for CURB-65, the latter being significantly lower than the first three. CONCLUSIONS: The MEDS, SOFA, and APACHE II are adequate scoring systems for predicting mortality and complications in septic patients. It is essential to utilize these scoring systems in emergency medical assistance in hospitals in Peru. PMID- 27384623 TI - [Characteristics of mistreatment in medical students of a public university in Peru]. AB - OBJECTIVES: To determine the characteristics of mistreatment among medical students at a public university in the province Ica, Peru. MATERIALS AND METHODS: This cross-sectional study was performed in 2012, and used a probability sample of medical students (freshman to sixth year) at the Universidad Nacional San Luis Gonzaga. A 23-item survey with a Likert scale was used to measure the students' perceptions of psychological, physical, academic and sexual mistreatment. Univariate and bivariate statistical analysis were performed. RESULTS: A total of 281 students were surveyed. The perception of psychological mistreatment was 96.8%; academic, 86.8%; physical, 62.6% and sexual, 20.6%. Physical abuse increased during the clinical-surgical study cicle (p = 0.001). Medical doctors and residents were the main aggressors. Male students reported of receiving assignments as a punishment, not receiving credits for their work, physical mistreatment, verbal threats, insults, or being teased because of their etnic background. Female students were more likely to have experienced sexual abuse. Report of sexual abuse frequently ocurred at the university (45.3%, p=0.002) and hospital (45.0%, p=0.046). Women frequently reported not knowing to whom or where to denounce the abuse (54.6%, p=0.042) and not reporting it because it stopped (56.9%, p=0.048). CONCLUSIONS: There is a high prevalence of abuse among students in which their characteristics as sex, level of study and aggressor allow to identify the types of abuse that they receive. PMID- 27384624 TI - [Evaluation of peruvian money test in screening of cognitive impairment among older adults]. AB - Objectives To evaluate the Peruvian adaptation of the money test (Eurotest) for identifying cognitive impairment among >60-year-old adults. Materials and methods This is a phase I study of diagnostic test, with a convenience sampling and calculation of the test's sensitivity and specificity, based on a pretest prevalence of 50%. The criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) and Global Deterioration Scale (GDS) were used for the operational definition of patients with cognitive impairment. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal cut-off value. Results The study evaluated 42 cases and 42 controls; there was no significant difference between age (77.88 +/- 6.01 years vs. 6.49 76.14 +/- years) and years of education (13.69 +/- 3.70 years vs. 8.17 +/- 4.71 years). The Peruvian version of the Eurotest has a sensitivity of 90.5% and specificity of 83.3% with cut-off value of 24. Conclusions The Peruvian adapted version of the Eurotest, called prueba de la moneda peruana could be useful in screening for cognitive impairment among older adults. PMID- 27384625 TI - [Microbiological and therapeutic characteristics of confirmed neonatal sepsis at a hospital in Lima, Peru]. AB - OBJECTIVES: To describe the microbiological and therapeutic characteristics of confirmed neonatal sepsis, and determineits incidence and mortality, at the National Hospital Arzobispo Loayza (HNAL) from 2011 to 2012, Lima, Peru. MATERIALS AND METHODS: Retrospective longitudinal study. It was performed a monitoring to newborns with probable sepsis, and assessed the results from positive blood cultures. The newborns' characteristics were obtained from medical records. The acumulated incidences of confirmed sepsis, mortality and fatality rates were determined. Quantitative variables were reported as men +/- standard deviation or median (interquartile range). Qualitative variables were reported as relative frequencies and percentages. RESULTS: The incidence of confirmed sepsis was 4.1 per 1 000 live births (95% confidence interval [CI]: 2.7-5.5). The mortality rate was 0.97 per 1 000 live births (95% CI: 0.29-1.63) and the fatality rate was 23.5% (95% CI: 9-37). The most commonly isolated organism was coagulase-negative Staphylococcus, followed by Staphylococcus aureus, both with high rates of oxacillin resistance (90% and 66.6%, respectively). A 67% of the newborns were treated using ampicillin/amikacin or ampicillin/cefotaxime. Antibiotics were changed in 58% of the newborns because of poor clinical/laboratory evolution or blood culture results. In most cases the seconds antibiotic was vancomycin (42.8%). CONCLUSIONS: There is a high incidence of confirmed sepsis and a high fatality rate. The administered treatments were not consistent with the microbiological profiles. PMID- 27384626 TI - [Myths about organ donation on health personnel, potential recipients and relatives of potential donors in a peruvian hospital: a qualitative study]. AB - OBJECTIVES: To explore the myths regarding organ donation at a national hospital in Lambayeque, Peru during 2014. MATERIALS AND METHODS: A qualitative phenomenological study was performed using 24 unstructured in-depht interview of health personnel, potential recipients and relatives of potential donors. Sampling was intentional opinion-based, completed by theoretical saturation in each group. An interview guide was used, which was assessed by five experts, and data triangulation was performed. RESULTS: Twenty-three interviewees (95,8%) reported a favorable attitude towards organ donation. On their National Identification Document, thirteen (54,2%) had marked "no" for donation. The myths were: age or illness can preclude donation; that the recipient may experience the donor's behaviours and lives in it; brain death is undestood as the immobility of the body and a reversible state; religions do not accept organ donation because it affects physical integrity and resurrection; and that there are preferences on the organ donor waiting list and that organ trafficking taxes place. CONCLUSIONS: Myths explored in this study involved religious, socio-cultural, psychological and ethical misperceptions. The apparent lack of knowledge of the brain death diagnosis is the starting point of the donation process. Therefore, the presence of a hospital coordinator, the role of spiritual leaders and the correct information provided by media would be key parts to dispell these myths. PMID- 27384627 TI - [Potential vulnerability to flooding at public health facilities in four northern regions of Peru]. AB - In order to determine the potential vulnerability of public health facilities in four northern regions of Peru to the possible effects of El Nino-Southern Oscillation (ENSO) phenomenon. An exploratory spatial analysis was performed using the geo-referenced points for at-risk areas based on the activation of gullies that were reported by the National Water Authority, and the location of the four regional public health facilities of the Ministry of Health. Concentric areas of influence were simulate from the points of risk towards the public health facilities using radii of 200, 1000 and 1500 meters. The Tumbes region would be the most affected with 37.2% of its health facilities being affected by floods and landslides. The I-2 and I-3 categories of health facilities appeared to be the most affected with 28.9% and 31.6% respectively. Therefore, public health facilities near the risk zones may be affected by the ENSO. PMID- 27384628 TI - [Clinical characteristics of patients treated with electroconvulsive therapy in a public hospital in Peru]. AB - With the purpose of describe the profile of use of electroconvulsive therapy (ECT) on hospitalized patients at "Honorio Delgado - Hideyo Noguchi" National Institute of Mental Health in Lima, Peru, the medical records of patients receiving ECT between 2001 and 2011 were reviewed. The main findings were: four hundred and nineteen ECT courses were applied to 372 patients, with a total of 5439 applications the most common diagnosis was paranoid schizophrenia (70.7%), the most common indication was resistance to treatment (80.7%), also the clinical response to ECT was good in 70.1% of cases while side effects were generally transient and mild. The use of ECT decreased over the period of the study but it was tolerable and safe, especially in the modified version, and it had a high response rate so remains as a first-line psychiatric treatment. PMID- 27384629 TI - [Spatial distribution of accidents, incidents and diseases related to work in Peru, 2012-2014]. AB - We analyzed geospatially accidents, incidents and diseases related to work of regional reports in Peru (2012-2014). The 52887 events were classified as work related accidents (93%), dangerous incidents (5.1%), occupational diseases (1%) and fatal accidents (0.9%). The highest rates of fatal accidents were reported in Pasco, Callao, Lima, Moquegua and Arequipa. Callao and Lima are the regions with the highest rates of occupational accidents. The highest rates of dangerous incidents were reported in Arequipa, Callao, Lima, Ica and Piura. Occupational diseases are distributed with high rates in Huancavelica, Ancash, Pasco, Callao and Cusco. The economic activities that reported most of the occupational diseases were mining and quarrying (49.2%); followed by manufacturing industry (23.4%); and construction (8%). It is concluded that there are high rates and common spatial patterns of laboral accidents in Peru that could be used by decision makers to focus interventions. PMID- 27384630 TI - [Acute toxicity of Xanthium spinosum leaves in BALB/C mice]. AB - The leaves of the Xanthium spinosum plant have been used culturally in Paraguay for their medicinal properties. Acute toxicity of mature leaf extract was evaluated. For the study, 35 Balb/c mice were selected and allocated into 7 groups, 6 test groups and 1 control group. The extract was prepared in concentrations of 6% and 9% (g/dL). The 6% concentration was administrated to 3 test groups and 9% concentration to the remaining 3 groups, with doses between 200 and 1000 mg/kg per mouse. After 14 days of observation, blood samples were taken for laboratory studies of urea and transaminases and organs were examined for pathological studies. There were increased levels of GOT and urea in the test groups compared to the control group. In conclusion, the consumption of mature leaf extract of Xanthium spinosum can cause hepatic damage. PMID- 27384631 TI - [Psychological intervention to candidates for surgery bariatric in a public hospital in Brazil]. AB - We evaluated a psychological intervention program to patients eligible for bariatric surgery, performing lifting coping strategies, anxiety manifestations and lifestyle changes, comparing them to obese patients without exposure to the intervention. The cognitive-behavioral program consists of 12 group sessions, in which they are addressed issues relevant to the process of habit change and preparation for surgery. The comparison of pre and post-intervention and between groups showed improvements in the experimental group. It is highlighted the importance of continued counseling as a promoter of skills required to face adverse situations of obesity and treatment. Studies with larger samples, and more attention to anxiety variables are suggested. PMID- 27384632 TI - [Evolution of the climate change concept and its impact in the public health of Peru]. AB - The term "climate change" is not a new concept but its impact on public health is under constant review. We know that climate has already changed and will continue to change for centuries with the rise in average global temperature, and the associated rise in sea level. This fact makes mitigation efforts relevant only in the very long term and for generations of humans whose parents have not yet been born. When we talk about public health in the context of climate change, we are talking about adaptation. In the present, countries that are currently the most affected by climate change are precisely countries like Peru, without a significant carbon footprint at the global level but that are highly sensitive to the effects of climate. Without reliable climate projections, the health impact of climate change can be uncertain and complicated. Nevertheless, at the local level, every district can identify its vulnerabilities and define priorities to protect the health of its population. There are, and it can also be developed, environmental health indicators that can help monitor how well we are adapting and how prepared we are for changes in the climate. Adaptation to climate change implies improving living conditions, enhancing epidemiological surveillance systems and extending access to healthcare. The fight against the effects of climate change in public health is a fight against poverty and inequality, and that is nothing new in Peru. PMID- 27384633 TI - [Role of the health sector in climate change]. AB - This article compiles the conclusions and results of several studies conducted by global and intergovernmental organizations involved in the research and promotion of policies and strategies for a successful and efficient management of the negative effects of climate change in public health. It is also a call for awareness the health community regarding their protagonist and strategic role to be assumed in relation to this global phenomenon which requires the coordinated cross-sectoral and inter-institution collaboration to achieve true social and environmental resilience. PMID- 27384634 TI - [Peru, climate change and non-communicable diseases: ?where are we and where are we headed?]. AB - The world is facing a crisis of noncommunicable diseases alongside a state of climate volatility. Of the total health burden attributable to climate change, 99% will be assumed by developing countries. In light of climate change, Peru's best opportunity is to create mitigation and adaptation policies focused on developing health co-benefits, which will improve the state of noncommunicable diseases and the climate system. This article presents Peru's compromises in terms of mitigation of greenhouse gas emissions; identifies public health opportunities for Peru under the Paris Agreement signed in the 21st Conference of the Parties (COP21); and makes recommendations for evidence and policy generation for the National Academy of Medicine and the Peruvian government. PMID- 27384635 TI - [Network meta-analysis: mixed and indirect treatment comparisons. a new method to the service of clinical epidemiology and public health]. AB - This review describes essential concepts of network meta-analysis and indirect comparisons and their application to clinical science. There are an increasing number of systematic reviews and meta-analyses providing direct comparisons between different interventions, although this is often not feasible when there is a lack of evidence related to all possible comparisons. Thus, important statistical tools that help make indirect comparisons based on previously existing comparisons have been developed. Network meta-analyses are an innovative tool that could assist doctors, researchers, and governmental organizations when making clinical and public health decisions. PMID- 27384636 TI - [Suggestions for chikungunya control based on a sensitivity analysis of a mathematical model]. AB - Chikungunya fever seriously affects peoples' health and causes chronic joint pain and even disability. Chikungunya is transmitted by the bite of Aedes aegypti and Aedes albopictus. Outbreaks have been reported in throughout the world, including Latin America. Mathematical modeling studies of these outbreaks have calculated the values of various epidemiological parameters. Based on them, a mathematical model was prepared to simulate a chikungunya outbreak in a local population, which was transmitted from an neighboring infected population. A sensitivity and uncertainty analysis revealed that the mosquito-to-human and human-to-mosquito transmission rates are the variables with the highest correlation with the number infected people, which were greatest at 60 days after the first case in the neighboring population. Therefore, it is recommended to take this into consideration when planning policies to control such variables as isolation of infected people, distribution of mosquito netting and repellents, fumigation, among others. PMID- 27384637 TI - [Dermatomiositis and evans syndrome associated with HTLV-1 infection]. AB - A 55-year-old female patient, born in Ayacucho, with a history of dermatomyositis for 3 years, who received irregular treatment with prednisone. Two months prior to admission, she presented with autoinmune hemolytic anemia and idiopathic thrombocytopenic purpura. The patient received methylprednisolone pulse therapy and packed red blood cells transfusions. Upon admission, she was drowsy, with a poor overall status, marked weight loss, dehydration, with presence of livedo reticularis in her lower extremities, and onychodystrophy and onycholysis on the toes of both feet. Western blot test was positive for human T-lymphotropic virus type 1 (HTLV-1). The patient evolved with recurrent hypoglycemia. Therefore, we report a case of dermatomyositis and Evans syndrome in the context of an HTLV-1 infection. PMID- 27384638 TI - [Predatory capacity of trophozoites of Trichomonas hominis to destroy and/or phagocytose Blastocystis hominis]. PMID- 27384639 TI - [New distribution areas of Aedes aegypti in Peru]. PMID- 27384640 TI - [Internet use among diabetic patients searching for information about their disease. Lima, Peru, 2014]. PMID- 27384641 TI - [Malnutrition in institutionalized elderly in a nursing home. Lima, Peru]. PMID- 27384642 TI - [Acute Hepatitis A in patients with febrile illness in a hospital in the northern region of Peru]. PMID- 27384643 TI - [Knowledge about tuberculosis in pharmacy personnels in a district of Lima, Peru]. PMID- 27384644 TI - [Chronic symptoms after a dengue episode, a need for research]. PMID- 27384645 TI - [Teaching indigenous languages at peruvian medical schools]. PMID- 27384646 TI - [Spatial analysis of cardiovascular disease-related mortality in the provinces of Lima and Callao]. PMID- 27384647 TI - Modeling Hematologic and Biochemical Parameters with Spatiotemporal Analysis for the Free-Ranging Eastern Box Turtle (Terrapene carolina carolina) in Illinois and Tennessee, a Potential Biosentinel. AB - Box turtles are long-lived, inhabit both aquatic and terrestrial habitats, and have relatively small home ranges making them a suitable candidate as a sentinel. To characterize their changes in response to environmental health, assessment of observed variation of this species is required. Thus, a comparative health assessment was employed in 825 Eastern box turtles in east central Illinois and Oak Ridge, Tennessee, to establish a baseline health assessment with regard to sex, age class, season, and location, identify temporal trends, and map parameters. Hematological and plasma biochemical variables measured included packed cell volume, total solids, white blood cell and differential counts, calcium, phosphorus, aspartate aminotransferase, bile acids, creatine kinase, and uric acid. These variables were reduced to four principle components that explained 68.8 % of the cumulative variance. The top model included the main effects of year, location, and sex, but no interactions. Spatial analysis of turtles in Tennessee demonstrated increased WBC and decreased PCV in 2011 associated with a clear-cut silviculture site. The results of this health assessment can serve as a baseline of population health in future studies and aid in the utility of this species as a sentinel. PMID- 27384648 TI - Prevailing PA Mutation K356R in Avian Influenza H9N2 Virus Increases Mammalian Replication and Pathogenicity. AB - Adaptation of the viral polymerase complex comprising PB1, PB2, and PA is necessary for efficient influenza A virus replication in new host species. We found that PA mutation K356R (PA-K356R) has become predominant since 2014 in avian H9N2 viruses in China as with seasonal human H1N1 viruses. The same mutation is also found in most human isolates of emergent avian H7N9 and H10N8 viruses whose six internal gene segments are derived from the H9N2 virus. We further demonstrated the mammalian adaptive functionality of the PA-K356R mutation. Avian H9N2 virus with the PA-K356R mutation in human A549 cells showed increased nuclear accumulation of PA and increased viral polymerase activity that resulted in elevated levels of viral transcription and virus output. The same mutant virus in mice also enhanced virus replication and caused lethal infection. In addition, combined mutation of PA-K356R and PB2-E627K, a well-known mammalian adaptive marker, in the H9N2 virus showed further cooperative increases in virus production and severity of infection in vitro and in vivo In summary, PA-K356R behaves as a novel mammalian tropism mutation, which, along with other mutations such as PB2-E627K, might render avian H9N2 viruses adapted for human infection. IMPORTANCE: Mutations of the polymerase complex (PB1, PB2, and PA) of influenza A virus are necessary for viral adaptation to new hosts. This study reports a novel and predominant mammalian adaptive mutation, PA-K356R, in avian H9N2 viruses and human isolates of emergent H7N9 and H10N8 viruses. We found that PA-356R in H9N2 viruses causes significant increases in virus replication and severity of infection in human cells and mice and that PA-K356R cooperates with the PB2-E627K mutation, a well-characterized human adaptive marker, to exacerbate mammalian infection in vitro and in vivo Therefore, the PA-K356R mutation is a significant adaptation in H9N2 viruses and related H7N9 and H10N8 reassortants toward human infectivity. PMID- 27384649 TI - Virion Structure of Israeli Acute Bee Paralysis Virus. AB - The pollination services provided by the western honeybee (Apis mellifera) are critical for agricultural production and the diversity of wild flowering plants. However, honeybees suffer from environmental pollution, habitat loss, and pathogens, including viruses that can cause fatal diseases. Israeli acute bee paralysis virus (IAPV), from the family Dicistroviridae, has been shown to cause colony collapse disorder in the United States. Here, we present the IAPV virion structure determined to a resolution of 4.0 A and the structure of a pentamer of capsid protein protomers at a resolution of 2.7 A. IAPV has major capsid proteins VP1 and VP3 with noncanonical jellyroll beta-barrel folds composed of only seven instead of eight beta-strands, as is the rule for proteins of other viruses with the same fold. The maturation of dicistroviruses is connected to the cleavage of precursor capsid protein VP0 into subunits VP3 and VP4. We show that a putative catalytic site formed by the residues Asp-Asp-Phe of VP1 is optimally positioned to perform the cleavage. Furthermore, unlike many picornaviruses, IAPV does not contain a hydrophobic pocket in capsid protein VP1 that could be targeted by capsid-binding antiviral compounds. IMPORTANCE: Honeybee pollination is required for agricultural production and to sustain the biodiversity of wild flora. However, honeybee populations in Europe and North America are under pressure from pathogens, including viruses that cause colony losses. Viruses from the family Dicistroviridae can cause honeybee infections that are lethal, not only to individual honeybees, but to whole colonies. Here, we present the virion structure of an Aparavirus, Israeli acute bee paralysis virus (IAPV), a member of a complex of closely related viruses that are distributed worldwide. IAPV exhibits unique structural features not observed in other picorna-like viruses. Capsid protein VP1 of IAPV does not contain a hydrophobic pocket, implying that capsid-binding antiviral compounds that can prevent the replication of vertebrate picornaviruses may be ineffective against honeybee virus infections. PMID- 27384650 TI - Mapping Murine Corneal Neovascularization and Weight Loss Virulence Determinants in the Herpes Simplex Virus 1 Genome and the Detection of an Epistatic Interaction between the UL and IRS/US Regions. AB - Herpes simplex virus 1 (HSV-1) most commonly causes recrudescent labial ulcers; however, it is also the leading cause of infectious blindness in developed countries. Previous research in animal models has demonstrated that the severity of HSV-1 ocular disease is influenced by three main factors: host innate immunity, host immune response, and viral strain. We have previously shown that mixed infection with two avirulent HSV-1 strains (OD4 and CJ994) results in recombinants with a wide range of ocular disease phenotype severity. Recently, we developed a quantitative trait locus (QTL)-based computational approach (vQTLmap) to identify viral single nucleotide polymorphisms (SNPs) predicted to influence the severity of the ocular disease phenotypes. We have now applied vQTLmap to identify HSV-1 SNPs associated with corneal neovascularization and mean peak percentage weight loss (MPWL) using 65 HSV-1 OD4-CJ994 recombinants. The vQTLmap analysis using Random Forest for neovascularization identified phenotypically meaningful nonsynonymous SNPs in the ICP4, UL41 (VHS), UL42, UL46 (VP11/12), UL47 (VP13/14), UL48 (VP22), US3, US4 (gG), US6 (gD), and US7 (gI) coding regions. The ICP4 gene was previously identified as a corneal neovascularization determinant, validating the vQTLmap method. Further analysis detected an epistatic interaction for neovascularization between a segment of the unique long (UL) region and a segment of the inverted repeat short (IRS)/unique short (US) region. Ridge regression was used to identify MPWL-associated nonsynonymous SNPs in the UL1 (gL), UL2, UL4, UL49 (VP22), UL50, and ICP4 coding regions. The data provide additional insights into virulence gene and epistatic interaction discovery in HSV-1. IMPORTANCE: Herpes simplex virus 1 (HSV-1) typically causes recurrent cold sores; however, it is also the leading source of infectious blindness in developed countries. Corneal neovascularization is critical for the progression of blinding ocular disease, and weight loss is a measure of infection severity. Previous HSV-1 animal virulence studies have shown that the severity of ocular disease is partially due to the viral strain. In the current study, we used a recently described computational quantitative trait locus (QTL) approach in conjunction with 65 HSV-1 recombinants to identify viral single nucleotide polymorphisms (SNPs) involved in neovascularization and weight loss. Neovascularization SNPs were identified in the ICP4, VHS, UL42, VP11/12, VP13/14, VP22, gG, US3, gD, and gI genes. Further analysis revealed an epistatic interaction between the UL and US regions. MPWL-associated SNPs were detected in the UL1 (gL), UL2, UL4, VP22, UL50, and ICP4 genes. This approach will facilitate future HSV virulence studies. PMID- 27384651 TI - Infection of Common Marmosets with GB Virus B Chimeric Virus Encoding the Major Nonstructural Proteins NS2 to NS4A of Hepatitis C Virus. AB - A lack of immunocompetent-small-primate models has been an obstacle for developing hepatitis C virus (HCV) vaccines and affordable antiviral drugs. In this study, HCV/GB virus B (GBV-B) chimeric virus carrying the major nonstructural proteins NS2 to NS4A (HCV NS2 to -4A chimera) was produced and used to infect common marmosets, since HCV NS2 to NS4A proteins are critical proteases and major antigens. Seven marmosets were inoculated intrahepatically with HCV NS2 to -4A chimera RNA for primary infection or intravenously injected with chimera containing serum for passage infection. Three animals used as controls were injected with phosphate-buffered saline (PBS) or GBV-B, respectively. Six of seven HCV NS2 to -4A chimera-infected marmosets exhibited consistent viremia and one showed transient viremia during the course of follow-up detection. All six infected animals with persistent circulating viremia presented characteristics typical of viral hepatitis, including viral RNA and proteins in hepatocytes and histopathological changes in liver tissue. Viremia was consistently detected for 5 to 54 weeks of follow-up. FK506 immunosuppression facilitated the establishment of persistent chimera infection in marmosets. An animal with chimera infection spontaneously cleared the virus in blood 7 weeks following the first inoculation, but viral-RNA persistence, low-level viral protein, and mild necroinflammation remained in liver tissue. The specific antibody and T-cell response to HCV NS3 in this viremia-resolved marmoset was boosted by rechallenging, but no viremia was detected during 57 weeks of follow-up. The chimera-infected marmosets described can be used as a suitable small-primate animal model for studying novel antiviral drugs and T-cell-based vaccines against HCV infection. IMPORTANCE: HCV infection causes approximately 70% of chronic hepatitis and is frequently associated with primary liver cancer globally. Chimpanzees have been used as a reliable primate model for HCV infection, but ethical considerations have restricted their utility in biomedical research. GB virus B (GBV-B) is a flavivirus related to HCV. It can infect common marmosets, a New World small primate, and induces viral hepatitis similar to HCV infection in humans. To minimize differences between GBV-B and HCV, we generated HCV NS2 to -4A/GBV-B chimeric viruses and established a chimera infected marmoset model. HCV NS2 to -4A chimera-infected marmosets provide a small-animal model for evaluating novel antiviral drugs targeting HCV NS3-NS4A protease and T-cell-based HCV vaccines. PMID- 27384652 TI - The Interferon-Stimulated Gene Ifitm3 Restricts West Nile Virus Infection and Pathogenesis. AB - The interferon-induced transmembrane protein (IFITM) family of proteins inhibit infection of several different enveloped viruses in cell culture by virtue of their ability to restrict entry and fusion from late endosomes. As few studies have evaluated the importance of Ifitm3 in vivo in restricting viral pathogenesis, we investigated its significance as an antiviral gene against West Nile virus (WNV), an encephalitic flavivirus, in cells and mice. Ifitm3(-/-) mice were more vulnerable to lethal WNV infection, and this was associated with greater virus accumulation in peripheral organs and central nervous system tissues. As no difference in viral burden in the brain or spinal cord was observed after direct intracranial inoculation, Ifitm3 likely functions as an antiviral protein in nonneuronal cells. Consistent with this, Ifitm3(-/-) fibroblasts but not dendritic cells resulted in higher yields of WNV in multistep growth analyses. Moreover, transcomplementation experiments showed that Ifitm3 inhibited WNV infection independently of Ifitm1, Ifitm2, Ifitm5, and Ifitm6. Beyond a direct effect on viral infection in cells, analysis of the immune response in WNV-infected Ifitm3(-/-) mice showed decreases in the total number of B cells, CD4(+) T cells, and antigen-specific CD8(+) T cells. Finally, bone marrow chimera experiments demonstrated that Ifitm3 functioned in both radioresistant and radiosensitive cells, as higher levels of WNV were observed in the brain only when Ifitm3 was absent from both compartments. Our analyses suggest that Ifitm3 restricts WNV pathogenesis likely through multiple mechanisms, including the direct control of infection in subsets of cells. IMPORTANCE: As part of the mammalian host response to viral infections, hundreds of interferon-stimulated genes (ISGs) are induced. The inhibitory activity of individual ISGs varies depending on the specific cell type and viral pathogen. Among ISGs, the genes encoding interferon-induced transmembrane protein (IFITM) have been reported to inhibit multiple families of viruses in cell culture. However, few reports have evaluated the impact of IFITM genes on viral pathogenesis in vivo In this study, we characterized the antiviral activity of Ifitm3 against West Nile virus (WNV), an encephalitic flavivirus, using mice with a targeted gene deletion of Ifitm3 Based on extensive virological and immunological analyses, we determined that Ifitm3 protects mice from WNV-induced mortality by restricting virus accumulation in peripheral organs and, subsequently, in central nervous system tissues. Our data suggest that Ifitm3 restricts WNV pathogenesis by multiple mechanisms and functions in part by controlling infection in different cell types. PMID- 27384653 TI - A Highly Conserved gp120 Inner Domain Residue Modulates Env Conformation and Trimer Stability. AB - Previous studies have shown that highly conserved residues in the inner domain of gp120 are required for HIV-1 envelope glycoprotein (Env) transitions to the CD4 bound conformation (A. Finzi, S. H. Xiang, B. Pacheco, L. Wang, J. Haight, et al., Mol Cell 37:656-667, 2010, http://dx.doi.org/10.1016/j.molcel.2010.02.012; A. Desormeaux, M. Coutu, H. Medjahed, B. Pacheco, A. Herschhorn, et al., J Virol 87:2549-2562, 2013, http://dx.doi.org/10.1128/JVI.03104-12). Moreover, W69, a highly conserved residue located at the interface between layer 1 and layer 2 of the inner domain, was recently shown to be important for efficient Env recognition by CD4-induced (CD4i) antibodies capable of potent antibody-dependent cellular cytotoxicity (W. D. Tolbert, N. Gohain, M. Veillette, J. P. Chapleau, C. Orlandi, et al., 2016, Structure 24:697-709, http://dx.doi.org/10.1016/j.str.2016.03.005; S. Ding, M. Veillette, M. Coutu, J. Prevost, L. Scharf, et al., 2016, J Virol 90:2127-2134, http://dx.doi.org/10.1128/JVI.02779-15). We evaluated the contribution of the hydrophobicity of W69 to conformational changes of Env by replacing it with a series of residues with aliphatic or aromatic side chains of decreasing chain length. We have found that the hydrophobicity of residue 69 is important for Env processing, CD4 binding, and its transition to the CD4-bound conformation. The most deleterious effect was observed when W69 was replaced with alanine or glycine residues. However, the functions lost due to W69 mutations could be progressively restored with amino acids of increasing aliphatic chain length and fully recovered with residues bearing an aromatic ring. Interestingly, poor CD4 binding of W69A could be fully restored by introducing a compensatory mutation within layer 2 (S115W). Structural studies of HIV-1 gp120 coree W69A/S115W mutant bound to the CD4 peptide mimetic M48U1 and Fab of anti-cluster A antibody N60-i3 revealed no perturbations to the overall structure of the double mutant compared to the wild-type protein but identified higher mobility within the interface between layer 1 and layer 2, the bridging sheet region, and the CD4 binding site.IMPORTANCE HIV-1 Env transitions to the CD4-bound conformation are required for viral entry. Previous studies identified a highly conserved residue of the inner domain, W69, as being involved in these conformational transitions (A. Finzi, S. H. Xiang, B. Pacheco, L. Wang, J. Haight, et al., Mol Cell 37:656-667, 2010, http://dx.doi.org/10.1016/j.molcel.2010.02.012). Here, we show that W69, located at the interface between gp120 and gp41 in the PGT151-bound trimer, plays a critical role in the interprotomer signaling induced by CD4 binding. This new information might be useful in immunogen design. PMID- 27384654 TI - CD25+ FoxP3+ Memory CD4 T Cells Are Frequent Targets of HIV Infection In Vivo. AB - Interleukin 2 (IL-2) signaling through the IL-2 receptor alpha chain (CD25) facilitates HIV replication in vitro and facilitates homeostatic proliferation of CD25(+) FoxP3(+) CD4(+) T cells. CD25(+) FoxP3(+) CD4(+) T cells may therefore constitute a suitable subset for HIV infection and plasma virion production. CD25(+) FoxP3(+) CD4(+) T cell frequencies, absolute numbers, and the expression of CCR5 and cell cycle marker Ki67 were studied in peripheral blood from HIV(+) and HIV(-) study volunteers. Different memory CD4(+) T cell subsets were then sorted for quantification of cell-associated HIV DNA and phylogenetic analyses of the highly variable EnvV1V3 region in comparison to plasma-derived virus sequences. In HIV(+) subjects, 51% (median) of CD25(+) FoxP3(+) CD4(+) T cells expressed the HIV coreceptor CCR5. Very high frequencies of Ki67(+) cells were detected in CD25(+) FoxP3(+) memory CD4(+) T cells (median, 27.6%) in comparison to CD25(-) FoxP3(-) memory CD4(+) T cells (median, 4.1%; P < 0.0001). HIV DNA content was 15-fold higher in CD25(+) FoxP3(+) memory CD4(+) T cells than in CD25(-) FoxP3(-) T cells (P = 0.003). EnvV1V3 sequences derived from CD25(+) FoxP3(+) memory CD4(+) T cells did not preferentially cluster with plasma-derived sequences. Quasi-identical cell-plasma sequence pairs were rare, and their proportion decreased with the estimated HIV infection duration. These data suggest that specific cellular characteristics of CD25(+) FoxP3(+) memory CD4(+) T cells might facilitate efficient HIV infection in vivo and passage of HIV DNA to cell progeny in the absence of active viral replication. The contribution of this cell population to plasma virion production remains unclear. IMPORTANCE: Despite recent advances in the understanding of AIDS virus pathogenesis, which cell subsets support HIV infection and replication in vivo is incompletely understood. In vitro, the IL-2 signaling pathway and IL-2-dependent cell cycle induction are essential for HIV infection of stimulated T cells. CD25(+) FoxP3(+) memory CD4 T cells, often referred to as regulatory CD4 T cells, depend on IL-2 signaling for homeostatic proliferation in vivo Our results show that CD25(+) FoxP3(+) memory CD4(+) T cells often express the HIV coreceptor CCR5, are significantly more proliferative, and contain more HIV DNA than CD25(-) FoxP3(-) memory CD4 T cell subsets. The specific cellular characteristics of CD25(+) FoxP3(+) memory CD4(+) T cells probably facilitate efficient HIV infection in vivo and passage of HIV DNA to cell progeny in the absence of active viral replication. However, the contribution of this cell subset to plasma viremia remains unclear. PMID- 27384655 TI - Regulatory Interaction between the Cellular Restriction Factor IFI16 and Viral pp65 (pUL83) Modulates Viral Gene Expression and IFI16 Protein Stability. AB - A key player in the intrinsic resistance against human cytomegalovirus (HCMV) is the interferon-gamma-inducible protein 16 (IFI16), which behaves as a viral DNA sensor in the first hours postinfection and as a repressor of viral gene transcription in the later stages. Previous studies on HCMV replication demonstrated that IFI16 binds to the viral protein kinase pUL97, undergoes phosphorylation, and relocalizes to the cytoplasm of infected cells. In this study, we demonstrate that the tegument protein pp65 (pUL83) recruits IFI16 to the promoter of the UL54 gene and downregulates viral replication, as shown by use of the HCMV mutant v65Stop, which lacks pp65 expression. Interestingly, at late time points of HCMV infection, IFI16 is stabilized by its interaction with pp65, which stood in contrast to IFI16 degradation, observed in herpes simplex virus 1 (HSV-1)-infected cells. Moreover, we found that its translocation to the cytoplasm, in addition to pUL97, strictly depends on pp65, as demonstrated with the HCMV mutant RV-VM1, which expresses a form of pp65 unable to translocate into the cytoplasm. Thus, these data reveal a dual role for pp65: during early infection, it modulates IFI16 activity at the promoter of immediate-early and early genes; subsequently, it delocalizes IFI16 from the nucleus into the cytoplasm, thereby stabilizing and protecting it from degradation. Overall, these data identify a novel activity of the pp65/IFI16 interactome involved in the regulation of UL54 gene expression and IFI16 stability during early and late phases of HCMV replication. IMPORTANCE: The DNA sensor IFI16, a member of the PYHIN proteins, restricts HCMV replication by impairing viral DNA synthesis. Using a mutant virus lacking the tegument protein pp65 (v65Stop), we demonstrate that pp65 recruits IFI16 to the early UL54 gene promoter. As a putative counteraction to its restriction activity, pp65 supports the nucleocytoplasmic export of IFI16, which was demonstrated with the viral mutant RV-VM1 expressing a nuclearly retained pp65. These data reveal a dual role of pp65 in IFI16 regulation: in the early phase of HCMV infection, it contributes to viral evasion from IFI16 restriction activity, while at later time points, it promotes the nuclear delocalization of IFI16, thereby stabilizing and protecting it from degradation. In the present work, we further clarify the mechanisms HCMV relies on to overcome intracellular innate immune restriction and provide new insights into the relevance of DNA-sensing restriction factor IFI16 during HCMV infection. PMID- 27384656 TI - Porcine Epidemic Diarrhea Virus Infection Inhibits Interferon Signaling by Targeted Degradation of STAT1. AB - Porcine epidemic diarrhea virus (PEDV) is a worldwide-distributed alphacoronavirus, but the pathogenesis of PEDV infection is not fully characterized. During virus infection, type I interferon (IFN) is a key mediator of innate antiviral responses. Most coronaviruses develop some strategy for at least partially circumventing the IFN response by limiting the production of IFN and by delaying the activation of the IFN response. However, the molecular mechanisms by which PEDV antagonizes the antiviral effects of interferon have not been fully characterized. Especially, how PEDV impacts IFN signaling components has yet to be elucidated. In this study, we observed that PEDV was relatively resistant to treatment with type I IFN. Western blot analysis showed that STAT1 expression was markedly reduced in PEDV-infected cells and that this reduction was not due to inhibition of STAT1 transcription. STAT1 downregulation was blocked by a proteasome inhibitor but not by an autophagy inhibitor, strongly implicating the ubiquitin-proteasome targeting degradation system. Since PEDV infection-induced STAT1 degradation was evident in cells pretreated with the general tyrosine kinase inhibitor, we conclude that STAT1 degradation is independent of the IFN signaling pathway. Furthermore, we report that PEDV induced STAT1 degradation inhibits IFN-alpha signal transduction pathways. Pharmacological inhibition of STAT1 degradation rescued the ability of the host to suppress virus replication. Collectively, these data show that PEDV is capable of subverting the type I interferon response by inducing STAT1 degradation. IMPORTANCE: In this study, we show that PEDV is resistant to the antiviral effect of IFN. The molecular mechanism is the degradation of STAT1 by PEDV infection in a proteasome-dependent manner. This PEDV infection-induced STAT1 degradation contributes to PEDV replication. Our findings reveal a new mechanism evolved by PEDV to circumvent the host antiviral response. PMID- 27384657 TI - Roles of the Rabies Virus Phosphoprotein Isoforms in Pathogenesis. AB - Rabies virus (RABV) P gene mRNA encodes five in-frame start codons, resulting in expression of full-length P protein (P1) and N-terminally truncated P proteins (tPs), designated P2, P3, P4, and P5. Despite the fact that some tPs are known as interferon (IFN) antagonists, the importance of tPs in the pathogenesis of RABV is still unclear. In this study, to examine whether tPs contribute to pathogenesis, we exploited a reverse genetics approach to generate CE(NiP)DeltaP2 5, a mutant of pathogenic CE(NiP) in which the P gene was mutated by replacing all of the start codons (AUG) for tPs with AUA. We confirmed that while CE(NiP) expresses detectable levels of P2 and P3, CE(NiP)DeltaP2-5 has an impaired ability to express these tPs. After intramuscular inoculation, CE(NiP)DeltaP2-5 caused significantly lower morbidity and mortality rates in mice than did CE(NiP), indicating that tPs play a critical role in RABV neuroinvasiveness. Further examinations revealed that this less neuroinvasive phenotype of CE(NiP)DeltaP2-5 correlates with its impaired ability to replicate in muscle cells, indicative of the importance of tPs in viral replication in muscle cells. We also demonstrated that CE(NiP)DeltaP2-5 infection induced a higher level of Ifn-beta gene expression in muscle cells than did CE(NiP) infection, consistent with the results of an IFN-beta promoter reporter assay suggesting that all tPs function to antagonize IFN induction in muscle cells. Taken together, our findings strongly suggest that tPs promote viral replication in muscle cells through their IFN antagonist activities and thereby support infection of peripheral nerves. IMPORTANCE: Despite the fact that previous studies have demonstrated that P2 and P3 of RABV have IFN antagonist activities, the actual importance of tPs in pathogenesis has remained unclear. Here, we provide the first evidence that tPs contribute to the pathogenesis of RABV, especially its neuroinvasiveness. Our results also show the mechanism underlying the neuroinvasiveness driven by tPs, highlighting the importance of their IFN antagonist activities, which support viral replication in muscle cells. PMID- 27384658 TI - The Molecular Determinants of Antibody Recognition and Antigenic Drift in the H3 Hemagglutinin of Swine Influenza A Virus. AB - Influenza A virus (IAV) of the H3 subtype is an important respiratory pathogen that affects both humans and swine. Vaccination to induce neutralizing antibodies against the surface glycoprotein hemagglutinin (HA) is the primary method used to control disease. However, due to antigenic drift, vaccine strains must be periodically updated. Six of the 7 positions previously identified in human seasonal H3 (positions 145, 155, 156, 158, 159, 189, and 193) were also indicated in swine H3 antigenic evolution. To experimentally test the effect on virus antigenicity of these 7 positions, substitutions were introduced into the HA of an isogenic swine lineage virus. We tested the antigenic effect of these introduced substitutions by using hemagglutination inhibition (HI) data with monovalent swine antisera and antigenic cartography to evaluate the antigenic phenotype of the mutant viruses. Combinations of substitutions within the antigenic motif caused significant changes in antigenicity. One virus mutant that varied at only two positions relative to the wild type had a >4-fold reduction in HI titers compared to homologous antisera. Potential changes in pathogenesis and transmission of the double mutant were evaluated in pigs. Although the double mutant had virus shedding titers and transmissibility comparable to those of the wild type, it caused a significantly lower percentage of lung lesions. Elucidating the antigenic effects of specific amino acid substitutions at these sites in swine H3 IAV has important implications for understanding IAV evolution within pigs as well as for improved vaccine development and control strategies in swine. IMPORTANCE: A key component of influenza virus evolution is antigenic drift mediated by the accumulation of amino acid substitutions in the hemagglutinin (HA) protein, resulting in escape from prior immunity generated by natural infection or vaccination. Understanding which amino acid positions of the HA contribute to the ability of the virus to avoid prior immunity is important for understanding antigenic evolution and informs vaccine efficacy predictions based on the genetic sequence data from currently circulating strains. Following our previous work characterizing antigenic phenotypes of contemporary wild-type swine H3 influenza viruses, we experimentally validated that substitutions at 6 amino acid positions in the HA protein have major effects on antigenicity. An improved understanding of the antigenic diversity of swine influenza will facilitate a rational approach for selecting more effective vaccine components to control the circulation of influenza in pigs and reduce the potential for zoonotic viruses to emerge. PMID- 27384659 TI - Specificity, Size, and Frequency of Spaces That Characterize the Mechanism of Bulk Transepithelial Transport of Prions in the Nasal Cavities of Hamsters and Mice. AB - Inhalation of infected brain homogenate results in transepithelial transport of prions across the nasal mucosa of hamsters, some of which occurs rapidly in relatively large amounts between cells (A. E. Kincaid, K. F. Hudson, M. W. Richey, and J. C. Bartz, J. Virol 86:12731-12740, 2012, doi:http://dx.doi.org/10.1128/JVI.01930-12). Bulk transepithelial transport in the nasal cavity has not been studied to date. In the present study, we characterized the frequency, size, and specificity of the intercellular spaces that mediate the bulk transport of inhaled prions between cells of mice or hamsters following extranasal inoculation with mock-infected brain homogenate, different strains of prion-infected brain homogenate, or brain homogenate mixed with India ink. Infected or mock-infected inoculum was identified within lymphatic vessels of the lamina propria and in spaces of >5 MUm between a small number of cells of the nasal mucosa in >90% of animals from 5 to 60 min after inhalation. The width of the spaces between cells, the amount of the inoculum within the lumen of lymphatic vessels, and the timing of the transport indicate that this type of transport was taking place through preexisting spaces in the nasal cavity that were orders of magnitude wider than what is normally reported for paracellular transport. The indiscriminate rapid bulk transport of brain homogenate in the nasal cavity results in immediate entry into nasal cavity lymphatics following inhalation. This novel mechanism may underlie the recent report of the early detection of prions in blood following inhalation and has implications for horizontal prion transmission. IMPORTANCE: The results of these studies demonstrate that the nasal mucosa of mice and hamsters is not an absolute anatomical barrier to inhaled prion-infected or uninfected brain homogenate. Relatively large amounts of infected and uninfected brain homogenate rapidly cross the nasal mucosa and enter the lumen of lymphatic vessels following inhalation. These bulk transepithelial transport events were relatively rare but present in >90% of animals 5 to 60 min following inhalation. This novel mechanism of bulk transepithelial transport was seen in experimental and control hamsters and mice, indicating that it was not species specific or in response to prion exposure. The indiscriminate bulk intercellular transport of inhaled pathogens across the nasal mucosa followed by entry into the lymphatic system may be a mechanism that underlies the entry and spread of other toxins and pathogens in olfactory system-driven animals. PMID- 27384661 TI - Genetic Lineage and Reassortment of Influenza C Viruses Circulating between 1947 and 2014. AB - Since influenza C virus was first isolated in 1947, the virus has been only occasionally isolated by cell culture; there are only four strains for which complete genome sequences are registered. Here, we analyzed a total of 106 complete genomes, ranging from the first isolate from 1947 to recent isolates from 2014, to determine the genetic lineages of influenza C virus, the reassortment events, and the rates of nucleotide substitution. The results showed that there are six lineages, named C/Taylor, C/Mississippi, C/Aichi, C/Yamagata, C/Kanagawa, and C/Sao Paulo. They contain both antigenic and genetic lineages of the hemagglutinin-esterase (HE) gene, and the internal genes PB2, PB1, P3, NP, M, and NS are divided into two major lineages, a C/Mississippi/80-related lineage and a C/Yamagata/81-related lineage. Reassortment events were found over the entire period of 68 years. Several outbreaks of influenza C virus between 1990 and 2014 in Japan consisted of reassortant viruses, suggesting that the genomic constellation is related to influenza C virus epidemics. The nucleotide sequences were highly homologous to each other. The minimum percent identity between viruses ranged from 91.1% for the HE gene to 96.1% for the M gene, and the rate of nucleotide substitution for the HE gene was the highest, at 5.20 * 10(-4) substitutions/site/year. These results indicate that reassortment is an important factor that increases the genetic diversity of influenza C virus, resulting in its ability to prevail in humans. IMPORTANCE Influenza C virus is a pathogen that causes acute respiratory illness in children and results in hospitalization of infants. We previously demonstrated (Y. Matsuzaki et al., J Clin Virol 61:87-93, 2014, http://dx.doi.org/10.1016/j.jcv.2014.06.017) that periodic epidemics of this virus occurred in Japan between 1996 and 2014 and that replacement of the dominant antigenic group occurred every several years as a result of selection by herd immunity. However, the antigenicity of the HE glycoprotein is highly stable, and antigenic drift has not occurred for at least 30 years. Here, we analyzed a total of 106 complete genomes spanning 68 years for the first time, and we found that influenza C viruses are circulating worldwide while undergoing reassortment as well as selection by herd immunity, resulting in an increased ability to prevail in humans. The results presented in this study contribute to the understanding of the evolution, including reassortment events, underlying influenza C virus epidemics. PMID- 27384660 TI - Unusual Features of Sodium Taurocholate Cotransporting Polypeptide as a Hepatitis B Virus Receptor. AB - Cell culture (cc)-derived hepatitis B virus (HBV) can infect differentiated HepaRG cells, but efficient infection requires addition of polyethylene glycol (PEG) during inoculation. Identification of sodium taurocholate cotransporting polypeptide (NTCP) as an HBV receptor enabled ccHBV infection of NTCP reconstituted HepG2 cells, although very little hepatitis B surface antigen (HBsAg) is produced. We found infection by patient serum-derived HBV (sHBV), which required purification of viral particles through ultracentrifugation or PEG precipitation, was PEG independent and much more efficient in HepaRG cells than in HepG2/NTCP cells. In contrast to hepatitis B e antigen (HBeAg), HBsAg was not a reliable marker of productive sHBV infection at early time points. A low HBsAg/HBeAg ratio by ccHBV-infected HepG2/NTCP cells was attributable to dimethyl sulfoxide (DMSO) in culture medium, NTCP overexpression, and HBV genotype D. HepG2/NTCP cells released more viral antigens than HepG2 cells after HBV genome delivery by adeno-associated virus, and stable expression of NTCP in a ccHBV producing cell line increased viral mRNAs, proteins, replicative DNA, and covalently closed circular DNA. NTCP protein expression in HepG2/NTCP cells, despite being driven by the cytomegalovirus promoter, was markedly increased by DMSO treatment. This at least partly explains ability of DMSO to promote ccHBV infection in such cell lines. In conclusion, NTCP appeared inefficient to mediate infection by serum-derived HBV. It could promote HBV RNA transcription while inhibiting HBsAg secretion. Efficient PEG-independent sHBV infection of HepaRG cells permits comparative studies of diverse clinical HBV isolates and will help identify additional factors on virion surface promoting attachment to hepatocytes. IMPORTANCE: Currently in vitro infection with hepatitis B virus (HBV) depends on cell culture-derived HBV inoculated in the presence of polyethylene glycol. We found patient serum-derived HBV could efficiently infect differentiated HepaRG cells independent of polyethylene glycol, which represents a more physiological infection system. Serum-derived HBV has poor infectivity in HepG2 cells reconstituted with sodium taurocholate cotransporting polypeptide (NTCP), the currently accepted HBV receptor. Moreover, HepG2/NTCP cells secreted very little hepatitis B surface antigen after infection with cell culture-derived HBV, which was attributed to NTCP overexpression, genotype D virus, and dimethyl sulfoxide added to culture medium. NTCP could promote HBV RNA transcription, protein expression, and DNA replication in HepG2 cells stably transfected with HBV DNA, while dimethyl sulfoxide could increase NTCP protein level despite transcriptional control by a cytomegalovirus promoter. Therefore, this study revealed several unusual features of NTCP as an HBV receptor and established conditions for efficient serum virus infection in vitro. PMID- 27384662 TI - Endogenous Gibbon Ape Leukemia Virus Identified in a Rodent (Melomys burtoni subsp.) from Wallacea (Indonesia). AB - Gibbon ape leukemia virus (GALV) and koala retrovirus (KoRV) most likely originated from a cross-species transmission of an ancestral retrovirus into koalas and gibbons via one or more intermediate as-yet-unknown hosts. A virus highly similar to GALV has been identified in an Australian native rodent (Melomys burtoni) after extensive screening of Australian wildlife. GALV-like viruses have also been discovered in several Southeast Asian species, although screening has not been extensive and viruses discovered to date are only distantly related to GALV. We therefore screened 26 Southeast Asian rodent species for KoRV- and GALV-like sequences, using hybridization capture and high throughput sequencing, in the attempt to identify potential GALV and KoRV hosts. Only the individuals belonging to a newly discovered subspecies of Melomys burtoni from Indonesia were positive, yielding an endogenous provirus very closely related to a strain of GALV. The sequence of the critical receptor domain for GALV infection in the Indonesian M. burtoni subsp. was consistent with the susceptibility of the species to GALV infection. The second record of a GALV in M. burtoni provides further evidence that M. burtoni, and potentially other lineages within the widespread subfamily Murinae, may play a role in the spread of GALV-like viruses. The discovery of a GALV in the most western part of the Australo-Papuan distribution of M. burtoni, specifically in a transitional zone between Asia and Australia (Wallacea), may be relevant to the cross-species transmission to gibbons in Southeast Asia and broadens the known distribution of GALVs in wild rodents. IMPORTANCE: Gibbon ape leukemia virus (GALV) and the koala retrovirus (KoRV) are very closely related, yet their hosts neither are closely related nor overlap geographically. Direct cross-species infection between koalas and gibbons is unlikely. Therefore, GALV and KoRV may have arisen via a cross species transfer from an intermediate host whose range overlaps those of both gibbons and koalas. Using hybridization capture and high-throughput sequencing, we have screened a wide range of rodent candidate hosts from Southeast Asia for KoRV- and GALV-like sequences. Only a Melomys burtoni subspecies from Wallacea (Indonesia) was positive for GALV. We report the genome sequence of this newly identified GALV, the critical domain for infection of its potential cellular receptor, and its phylogenetic relationships with the other previously characterized GALVs. We hypothesize that Melomys burtoni, and potentially related lineages with an Australo-Papuan distribution, may have played a key role in cross-species transmission to other taxa. PMID- 27384663 TI - Comprehensive Characterization of HIV-1 Molecular Epidemiology and Demographic History in the Brazilian Region Most Heavily Affected by AIDS. AB - The high incidence of AIDS cases and the dominance of HIV-1 subtype C infections are two features that distinguish the HIV-1 epidemic in the two southernmost Brazilian states (Rio Grande do Sul [RS] and Santa Catarina [SC]) from the epidemic in other parts of the country. Nevertheless, previous studies on HIV molecular epidemiology were conducted mainly in capital cities, and a more comprehensive understanding of factors driving this unique epidemic in Brazil is necessary. Blood samples were collected from individuals in 13 municipalities in the Brazilian southern region. HIV-1 env and pol genes were submitted to phylogenetic analyses for assignment of subtype, and viral population phylodynamics were reconstructed by applying Skygrid and logistic coalescent models in a Bayesian analysis. A high prevalence of subtype C was observed in all sampled locations; however, an increased frequency of recombinant strains was found in RS, with evidence for new circulating forms (CRFs). In the SC state, subtype B and C epidemics were associated with distinct exposure groups. Although logistic models estimated similar growth rates for HIV-1 subtype C (HIV-1C) and HIV-1B, a Skygrid plot reveals that the former epidemic has been expanding for a longer time. Our results highlight a consistent expansion of HIV-1C in south Brazil, and we also discuss how heterosexual and men who have sex with men (MSM) transmission chains might have impacted the current prevalence of HIV-1 subtypes in this region. IMPORTANCE: The AIDS epidemic in south Brazil is expanding rapidly, but the circumstances driving this condition are not well known. A high prevalence of HIV-1 subtype C was reported in the capital cities of this region, in contrast to the subtype B dominance in the rest of the country. This study sought to comparatively investigate the HIV-1 subtype B and C epidemics by sampling individuals from several cities in the two states with the highest AIDS incidences in Brazil. Our analyses showed distinct epidemic growth curves for the two epidemics, and we also found evidence suggesting that separate transmission chains may be impacting the viral phylodynamics and the emergence of new recombinant forms. PMID- 27384664 TI - Genome-Wide Screening of Retroviral Envelope Genes in the Nine-Banded Armadillo (Dasypus novemcinctus, Xenarthra) Reveals an Unfixed Chimeric Endogenous Betaretrovirus Using the ASCT2 Receptor. AB - Retroviruses enter host cells through the interaction of their envelope (Env) protein with a cell surface receptor, which triggers the fusion of viral and cellular membranes. The sodium-dependent neutral amino acid transporter ASCT2 is the common receptor of the large RD114 retrovirus interference group, whose members display frequent env recombination events. Germ line retrovirus infections have led to numerous inherited endogenous retroviruses (ERVs) in vertebrate genomes, which provide useful insights into the coevolutionary history of retroviruses and their hosts. Rare ERV-derived genes display conserved viral functions, as illustrated by the fusogenic syncytin env genes involved in placentation. Here, we searched for functional env genes in the nine-banded armadillo (Dasypus novemcinctus) genome and identified dasy-env1.1, which clusters with RD114 interference group env genes and with two syncytin genes sharing ASCT2 receptor usage. Using ex vivo pseudotyping and cell-cell fusion assays, we demonstrated that the Dasy-Env1.1 protein is fusogenic and can use both human and armadillo ASCT2s as receptors. This gammaretroviral env gene belongs to a provirus with betaretrovirus-like features, suggesting acquisition through recombination. Provirus insertion was found in several Dasypus species, where it has not reached fixation, whereas related family members integrated before diversification of the genus Dasypus >12 million years ago (Mya). This newly described ERV lineage is potentially useful as a population genetic marker. Our results extend the usage of ASCT2 as a retrovirus receptor to the mammalian clade Xenarthra and suggest that the acquisition of an ASCT2-interacting env gene is a major selective force driving the emergence of numerous chimeric viruses in vertebrates. IMPORTANCE: Retroviral infection is initiated by the binding of the viral envelope glycoprotein to a host cell receptor(s), triggering membrane fusion. Ancient germ line infections have generated numerous endogenous retroviruses (ERVs) in nearly all vertebrate genomes. Here, we report a previously uncharacterized ERV lineage from the genome of a xenarthran species, the nine-banded armadillo (Dasypus novemcinctus). It entered the Dasypus genus >12 Mya, with one element being inserted more recently in some Dasypus species, where it could serve as a useful marker for population genetics. This element exhibits an env gene, acquired by recombination events, with conserved viral fusogenic properties through binding to ASCT2, a receptor used by a wide range of recombinant retroviruses infecting other vertebrate orders. This specifies the ASCT2 transporter as a successful receptor for ERV endogenization and suggests that ASCT2-binding env acquisition events have favored the emergence of numerous chimeric viruses in a wide range of species. PMID- 27384666 TI - Tunable C2N Membrane for High Efficient Water Desalination. AB - Water scarcity represents one of the most serious global problems of our time and challenges the advancements in desalination techniques. Although water-filtering architectures based on graphene have greatly advanced the approach to high performance desalination membranes, the controlled-generation of nanopores with particular diameter is tricky and has stunted its wide applications. Here, through molecular dynamic simulations and first-principles calculations, we propose that the recently reported graphene-like carbon nitride (g-C2N) monolayer can serve as high efficient filters for water desalination. Taking the advantages of the intrisic nanoporous structure and excellent mechanical properties of g C2N, high water transparency and strong salt filtering capability have been demonstrated in our simulations. More importantly, the "open" and "closed" states of the g-C2N filter can be precisely regulated by tensile strain. It is found that the water permeability of g-C2N is significantly higher than that reported for graphene filters by almost one order of magnitude. In the light of the abundant family of graphene-like carbon nitride monolayered materials, our results thus offer a promising approach to the design of high efficient filteration architectures. PMID- 27384665 TI - Structure-Activity Relationships of the Human Immunodeficiency Virus Type 1 Maturation Inhibitor PF-46396. AB - HIV-1 maturation inhibitors are a novel class of antiretroviral compounds that consist of two structurally distinct chemical classes: betulinic acid derivatives and the pyridone-based compound PF-46396. It is currently believed that both classes act by similar modes of action to generate aberrant noninfectious particles via inhibition of CA-SP1 cleavage during Gag proteolytic processing. In this study, we utilized a series of novel analogues with decreasing similarity to PF-46396 to determine the chemical groups within PF-46396 that contribute to antiviral activity, Gag binding, and the relationship between these essential properties. A spectrum of antiviral activity (active, intermediate, and inactive) was observed across the analogue series with respect to CA-SP1 cleavage and HIV-1 (NL4-3) replication kinetics in Jurkat T cells. We demonstrate that selected inactive analogues are incorporated into wild-type (WT) immature particles and that one inactive analogue is capable of interfering with PF-46396 inhibition of CA-SP1 cleavage. Mutations that confer PF-46396 resistance can impose a defective phenotype on HIV-1 that can be rescued in a compound-dependent manner. Some inactive analogues retained the capacity to rescue PF-46396-dependent mutants (SP1-A3V, SP1-A3T, and CA-P157S), implying that they can also interact with mutant Gag. The structure-activity relationships observed in this study demonstrate that (i) the tert-butyl group is essential for antiviral activity but is not an absolute requirement for Gag binding, (ii) the trifluoromethyl group is optimal but not essential for antiviral activity, and (iii) the 2-aminoindan group is important for antiviral activity and Gag binding but is not essential, as its replacement is tolerated. IMPORTANCE: Combinations of antiretroviral drugs successfully treat HIV/AIDS patients; however, drug resistance problems make the development of new mechanistic drug classes an ongoing priority. HIV-1 maturation inhibitors are novel as they target the Gag protein, specifically by inhibiting CA-SP1 proteolytic cleavage. The lack of high-resolution structural information of the CA-SP1 target in Gag has hindered our understanding of the inhibitor binding pocket and maturation inhibitor mode of action. Therefore, we utilized analogues of the maturation inhibitor PF-46396 as chemical tools to determine the chemical components of PF-46396 that contribute to antiviral activity and Gag binding and the relationship between these essential properties. This is the first study to report structure-activity relationships of the maturation inhibitor PF-46396. PF-46396 is chemically distinct from betulinic acid-derived maturation inhibitors; therefore, our data provide a foundation of knowledge that will aid our understanding of how structurally distinct maturation inhibitors act by similar modes of action. PMID- 27384668 TI - Correction: Sparstolonin B, a Novel Plant Derived Compound, Arrests Cell Cycle and Induces Apoptosis in N-Myc Amplified and N-Myc Nonamplified Neuroblastoma Cells. AB - [This corrects the article DOI: 10.1371/journal.pone.0096343.]. PMID- 27384667 TI - The "Ram Effect": A "Non-Classical" Mechanism for Inducing LH Surges in Sheep. AB - During spring sheep do not normally ovulate but exposure to a ram can induce ovulation. In some ewes an LH surge is induced immediately after exposure to a ram thus raising questions about the control of this precocious LH surge. Our first aim was to determine the plasma concentrations of oestradiol (E2) E2 in anoestrous ewes before and after the "ram effect" in ewes that had a "precocious" LH surge (starting within 6 hours), a "normal" surge (between 6 and 28h) and "late" surge (not detected by 56h). In another experiment we tested if a small increase in circulating E2 could induce an LH surge in anoestrus ewes. The concentration of E2 significantly was not different at the time of ram introduction among ewes with the three types of LH surge. "Precocious" LH surges were not preceded by a large increase in E2 unlike "normal" surges and small elevations of circulating E2 alone were unable to induce LH surges. These results show that the "precocious" LH surge was not the result of E2 positive feedback. Our second aim was to test if noradrenaline (NA) is involved in the LH response to the "ram effect". Using double labelling for Fos and tyrosine hydroxylase (TH) we showed that exposure of anoestrous ewes to a ram induced a higher density of cells positive for both in the A1 nucleus and the Locus Coeruleus complex compared to unstimulated controls. Finally, the administration by retrodialysis into the preoptic area, of NA increased the proportion of ewes with an LH response to ram odor whereas treatment with the alpha1 antagonist Prazosin decreased the LH pulse frequency and amplitude induced by a sexually active ram. Collectively these results suggest that in anoestrous ewes NA is involved in ram induced LH secretion as observed in other induced ovulators. PMID- 27384669 TI - Content Validity for the VVSymQ(r) Instrument: A New Patient-Reported Outcome Measure for the Assessment of Varicose Veins Symptoms. AB - BACKGROUND: Varicose veins are common and can impact patients' quality of life, but consensus regarding the evaluation of varicose vein symptoms is lacking and existing measures have limitations. OBJECTIVE: This research aimed to develop and establish the content validity of a new electronic patient-reported outcome (PRO) measure, the VVSymQ(r) instrument, to assess symptoms of superficial venous insufficiency (varicose veins) in clinical trials. METHODS: The development of the VVSymQ(r) instrument began with qualitative interviews with patients based on the symptom domain of the VEINES-QOL/Sym, an existing PRO instrument for chronic venous disorders of the leg. Three phases of qualitative research were conducted to examine the relevance and importance of the symptoms to patients with varicose veins, and the patients' ability to understand and use the VVSymQ(r) instrument. The development included evaluating questions that had 1-week and 24-h recall periods, and paper and electronic versions of the new instrument. RESULTS: Five symptoms (heaviness, achiness, swelling, throbbing, and itching [HASTITM]) were consistently reported by patients across all sources of qualitative data. The final version of the VVSymQ(r) instrument queries patients on the HASTITM symptoms using a 24-h recall period and a 6-point duration-based response scale ranging from "None of the time" to "All of the time," and is administered daily via an electronic diary. Cognitive interviews demonstrated varicose vein patients' understanding of and their ability to use the final version of the VVSymQ(r) instrument. CONCLUSION: Content validity was established for the VVSymQ(r) instrument, which assesses the five HASTITM symptoms of varicose veins daily via an electronic diary and has promise for use in research and practice. PMID- 27384670 TI - What Outcomes are Important for Gout Patients? In-Depth Qualitative Research into the Gout Patient Experience to Determine Optimal Endpoints for Evaluating Therapeutic Interventions. AB - BACKGROUND AND OBJECTIVES: Characterized by sudden onset of severe joint pain, swelling, redness, and tenderness to touch, gout 'flare ups' have a substantial impact on quality of life (QoL). This research employed a patient-centered approach to explore the symptoms and impacts of gout, and assess the content validity of existing patient-reported outcomes (PROs). METHODS: Qualitative interviews were conducted with 30 US gout patients (non-tophaceous: n = 20, tophaceous: n = 10) and five expert rheumatologists. Each interview included both concept elicitation (CE) questioning to learn about the patient experience and cognitive debriefing to assess the content validity of three PRO instruments (HAQ DI, GAQ, and TIQ-20). Nine of the patients provided further real-time qualitative data through a smart phone application. All qualitative data were subject to thematic analysis using Atlas.ti. Two patient advisors and three expert clinicians were engaged as advisors at key stages throughout the research. RESULTS: Interview and real-time data identified the same core symptoms and proximal impact concepts. Severe pain (typically in joints of extremities) was described as the cardinal symptom, often accompanied by swelling, redness, heat, sensitivity to touch, and stiffness. Domains of QoL impacted included physical functioning, sleep, daily activities, and work. The PRO instruments were generally well-understood by patients, but each included items with questionable relevance to at least some of the sample, dependent on the specific joints affected. CONCLUSIONS: Gout patients experience severe pain in affected joints, resulting in substantial limitations in physical functioning. Both the HAQ-DI and the TIQ-20 are useful for specific research purposes in the gout population, although modifications are recommended. PMID- 27384671 TI - Acquisition of Motor and Cognitive Skills through Repetition in Typically Developing Children. AB - BACKGROUND: Procedural memory allows acquisition, consolidation and use of motor skills and cognitive routines. Automation of procedures is achieved through repeated practice. In children, improvement in procedural skills is a consequence of natural neurobiological development and experience. METHODS: The aim of the present research was to make a preliminary evaluation and description of repetition-based improvement of procedures in typically developing children (TDC). Ninety TDC children aged 6-12 years were asked to perform two procedural learning tasks. In an assembly learning task, which requires predominantly motor skills, we measured the number of assembled pieces in 60 seconds. In a mirror drawing learning task, which requires more cognitive functions, we measured time spent and efficiency. Participants were tested four times for each task: three trials were consecutive and the fourth trial was performed after a 10-minute nonverbal interference task. The influence of repeated practice on performance was evaluated by means of the analysis of variance with repeated measures and the paired-sample test. Correlation coefficients and simple linear regression test were used to examine the relationship between age and performance. RESULTS: TDC achieved higher scores in both tasks through repetition. Older children fitted more pieces than younger ones in assembling learning and they were faster and more efficient at the mirror drawing learning task. CONCLUSIONS: These findings indicate that three consecutive trials at a procedural task increased speed and efficiency, and that age affected basal performance in motor-cognitive procedures. PMID- 27384673 TI - Downregulation of the neonatal Fc receptor expression in non-small cell lung cancer tissue is associated with a poor prognosis. AB - Lung cancer is the leading cause of cancer-related death worldwide. Although the recommended tumor, node and metastasis (TNM) classification and stage determination are important to select therapeutic options for patients with non small cell lung carcinoma (NSCLC), additional molecular markers are required to indicate the prognosis, in particular within a specific stage, and help with the management of patients.Because neonatal Fc receptor (FcRn) has recently been involved in colon cancer immunosurveillance, we measured its expression in non cancerous and NSCLC lung tissues and evaluated its prognostic value in overall survival for patient with NSCLC. FcRn expression was determined at both mRNA and protein levels on cancerous and adjacent non-cancerous tissues from 80 NSCLC patients. In NSCLC, FcRn was mainly found in resident and tumor infiltrating immune cells. The corresponding mRNA and protein were significantly less abundant in lung tumor than non-cancerous tissue. Moreover, analysis of our cohort and datasets from the public data bases show that FCGRT mRNA down-regulation is a robust and independent, unfavorable predictive factor of NSCLC patient survival. We conclude that FCGRT mRNA expression may be a useful additional marker for immunoscoring, reflecting tumor immune system, and help in the decision-making process for NSCLC patients. PMID- 27384675 TI - White matter degeneration in subjective cognitive decline: a diffusion tensor imaging study. AB - Subjective cognitive decline (SCD) may be an at-risk stage of Alzheimer's disease (AD) occurring prior to amnestic mild cognitive impairment (aMCI). To examine white matter (WM) defects in SCD, diffusion images from 27 SCD (age=65.3+/-8.0), 35 aMCI (age=69.2+/-8.6) and 25 AD patients (age=68.3+/-9.4) and 37 normal controls (NC) (age=65.1+/-6.8) were compared using Tract-Based Spatial Statistics (TBSS). WM impairments common to the three patient groups were extracted, and fractional anisotropy (FA) values were averaged in each group. As compared to NC subjects, SCD patients displayed widespread WM alterations represented by decreased FA (p<0.05), increased mean diffusivity (MD; p<0.05), and increased radial diffusivity (RD; p<0.05). In addition, localized WM alterations showed increased axial diffusivity (AxD; p<0.05) similar to what was observed in aMCI and AD patients (p<0.05). In the shared WM impairment tracts, SCD patients had FA values between the NC group and the other two patient groups. In the NC and SCD groups, the AVLT-delayed recall score correlated with higher AxD (r=-0.333, p=0.045), MD (r=-0.351, p=0.03) and RD (r=-0.353, p=0.025). In both the aMCI and AD groups the diffusion parameters were highly correlated with cognitive scores. Our study suggests that SCD patients present with widespread WM changes, which may contribute to the early memory decline they experience. PMID- 27384676 TI - Efficacy and safety of cisplatin, dexamethasone, gemcitabine and pegaspargase (DDGP) regimen in newly diagnosed, advanced-stage extranodal natural killer/T cell lymphoma: interim analysis of a phase 4 study NCT01501149. AB - To explore a more effective treatment for newly diagnosed, advanced-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), we conducted a phase 4 study of the cisplatin, dexamethasone, gemcitabine, pegaspargase (DDGP) regimen. The primary end point was the 2-year progression-free survival (PFS) after the protocol treatment. Secondary endpoints included response rate (RR), overall survival (OS) and median survival time (MST). The interim analysis included data only from March 2011 to September 2013, who received six cycles of DDGP chemotherapy. A total of 25 eligible patients were enrolled. Seventeen patients (17/24, 70.83%) achieved complete response (CR) and four (4/24, 16.67%) achieved partial response (PR), three (3/24, 12.50%) had progressive disease (PD). The RR after treatment was 87.50%. After a median follow-up duration of 24.67 months (range 4-48 months). The 2-year PFS and OS rate were 61.80% (95% CI, 42.00% to 81.60%) and 68.50 % (95% CI, 48.70% to 88.30%), respectively. The MST was 36.55 months (95% CI, 29.41 months to 43.70 months). Grade 3/4 leukopenia occurred in fourteen patients (58.33%) and grade 3/4 thrombocytopenia occurred in eleven patients (45.83%). Twelve patients (50.00%) experienced Activated Partial Phromboplastin Ptime (APTT) elongation and fourteen patients (58.33%) experienced hypofibrinogenemia. In conclusion, DDGP regimen is an effective and tolerated treatment for newly diagnosed, advanced-stage ENKTL. This trial was registered at www.ClinicalTrials.gov as #NCT01501149. PMID- 27384677 TI - Stimulatory actions of IGF-I are mediated by IGF-IR cross-talk with GPER and DDR1 in mesothelioma and lung cancer cells. AB - Insulin-like growth factor-I (IGF-I)/IGF-I receptor (IGF-IR) system has been largely involved in the pathogenesis and development of various tumors. We have previously demonstrated that IGF-IR cooperates with the G-protein estrogen receptor (GPER) and the collagen receptor discoidin domain 1 (DDR1) that are implicated in cancer progression. Here, we provide novel evidence regarding the molecular mechanisms through which IGF-I/IGF-IR signaling triggers a functional cross-talk with GPER and DDR1 in both mesothelioma and lung cancer cells. In particular, we show that IGF-I activates the transduction network mediated by IGF IR leading to the up-regulation of GPER and its main target genes CTGF and EGR1 as well as the induction of DDR1 target genes like MATN-2, FBN-1, NOTCH 1 and HES 1. Of note, certain DDR1-mediated effects upon IGF-I stimulation required both IGF-IR and GPER as determined knocking-down the expression of these receptors. The aforementioned findings were nicely recapitulated in important biological outcomes like IGF-I promoted chemotaxis and migration of both mesothelioma and lung cancer cells. Overall, our data suggest that IGF-I/IGF-IR system triggers stimulatory actions through both GPER and DDR1 in aggressive tumors as mesothelioma and lung tumors. Hence, this novel signaling pathway may represent a further target in setting innovative anticancer strategies. PMID- 27384678 TI - Local hyperthermia in head and neck cancer: mechanism, application and advance. AB - Local hyperthermia (HT), particularly in conjunction with surgery, radiotherapy and chemotherapy was useful for the treatment of human malignant tumors including head and neck cancer. However, at present it suffered from many limitations such as thermal dose control, target treatment regions and discrimination between healthy and cancer cells. Recent developments in nanotechnology have introduced novel and smart therapeutic nanomaterials to local HT of head and neck cancer that basically take advantage of various targeting approaches. The aim of this paper is to give a brief review of the mechanism, methods and clinical applications of local HT in head and neck cancer, mainly focusing on photothermal therapy (PTT) and nanoparticle-based hyperthermia. PMID- 27384679 TI - Coumestrol inhibits autoantibody production through modulating Th1 response in experimental autoimmune thyroiditis. AB - Coumestrol is a common phytoestrogen found in plants and Chinese medicinal herbs. Its influences on experimental autoimmune thyroiditis (EAT) were investigated in this study. Female adult CBA/J mice were fed with drinking water containing 1% Tween80 only (Control group), 0.8 mg/l (L group) and 8 mg/l coumestrol (H group) from 6 to 15 weeks of age, respectively. Their serum coumestrol concentrations were determined by high performance liquid chromatography, which were undetectable, 43.70 +/- 21.74 ng/ml and 135.07 +/- 70.40 ng/ml, respectively. In addition, the mice (n = 14-16/group) were immunized twice with thyroglobulin (Tg) and Freund's adjuvant to induce EAT during the meantime. Although no overt changes in the extent of intrathyroidal mononuclear cell infiltration were shown in the two coumestrol-treated groups as compared with the controls, serum anti-Tg IgG2a, IgG3 and IgG1 titers, ratio of IgG2a to IgG1 and the percentage of T helper (Th)1 cells in the splenocytes were significantly reduced in the L group. Another consistent change was the significantly decreased expression of splenic IFN-gamma mRNA after low dose of coumestrol exposure. Uterine weight was also markedly reduced in the mice of L group. These findings suggest that coumestrol treatment may have some beneficial actions against thyroid-specific autoantibody production in the development of autoimmune thyroiditis through suppression of Th1 response due to its anti-estrogenic activity. PMID- 27384680 TI - Compounds from the marine sponge Cribrochalina vasculum offer a way to target IGF 1R mediated signaling in tumor cells. AB - In this work two acetylene alcohols, compound 1 and compound 2, which were isolated and identified from the sponge Cribrochalina vasculum, and which showed anti-tumor effects were further studied with respect to targets and action mechanisms. Gene expression analyses suggested insulin like growth factor receptor (IGF-1R) signaling to be instrumental in controlling anti-tumor efficacy of these compounds in non-small cell lung cancer (NSCLC). Indeed compounds 1 and 2 inhibited phosphorylation of IGF-1Rbeta as well as reduced its target signaling molecules IRS-1 and PDK1 allowing inhibition of pro-survival signaling. In silico docking indicated that compound 1 binds to the kinase domain of IGF-1R at the same binding site as the well known tyrosine kinase inhibitor AG1024. Indeed, cellular thermal shift assay (CETSA) confirmed that C. vasculum compound 1 binds to IGF-1R but not to the membrane localized tyrosine kinase receptor EGFR. Importantly, we demonstrate that compound 1 causes IGF-1Rbeta but not Insulin Receptor degradation specifically in tumor cells with no effects seen in normal diploid fibroblasts. Thus, these compounds hold potential as novel therapeutic agents targeting IGF-1R signaling for anti-tumor treatment. PMID- 27384681 TI - Expression of CDX2 in gastric cardia adenocarcinoma and its correlation with H. pylori and cell proliferation. AB - BACKGROUND: Gastric cardia cancer (GCC) is located in the distal stomach, and strongly correlates with atrophic gastritis and Helicobacter pylori (H.pylori) infection. Caudal-related homeobox transcription factor 2 (CDX2) is homeobox gene encoding an intestine-specific transcription factor usually expressed in the intestinal epithelium cells. However, in several recent published papers, CDX2 was found to be aberrantly expressed in gastric, thyroid and ovarian cancer. RESULTS: Higher expression of CDX2 was found in GCC tissues in comparison with non-malignant cardia mucosa (p<0.05). Moreover, immunohistochemical analysis demonstrated that CDX2 expression correlated with lymphatic metastasis. In addition, we found that CDX2 expression progressively increased with the level of H. pylori infection (p<0.05), and also correlated with cell proliferation, based on Ki67 staining. METHODS: To investigate the relationship between CDX2, cell proliferation and H. pylori infection, we detected CDX2, Ki62 and H.pylori expression in 83 non-malignant gastric cardia mucosacases and 60 GCC specimens in the Chaoshan area, a high-risk region for esophageal and gastric cardia cancer. CONCLUSION: These findings provide pathological evidence that H. pylori infectionis a driving force of gastric cardia carcinogenesis by upregulating CDX2 and inducing inflammation. These results provide new pathological evidence that H. pylori infection induces GCC tumorigenesis. PMID- 27384682 TI - Laparoscopic Band-Separated One Anastomosis Gastric Bypass. AB - BACKGROUND: This video demonstrates laparoscopic band-separated one anastomosis gastric bypass-combining the advantages of banding and gastric bypass without stapler and cutter use. This is basically a gastrojejunal loop bypass above an obstructive band in the upper stomach. MATERIALS AND SURGICAL TECHNIQUE: An adjustable low pressure "Medsil" gastric band was introduced in the abdomen and retracted through the retrogastric tunnel. The front wall of the stomach below the band was displaced in the upward direction through the ring band, increasing the size of the anterior portion of the stomach pouch so that a gastroenteroanastomosis could be created at this point. Gastro-gastric sutures were placed to create a gastro-gastric plication around the band and hold it in position. The band tubing was exteriorized and connected to a special port, which was secured to the abdominal wall fascia. A jejunal loop was created about 200 cm from the ligament of Treitz and anastomosed to the gastric pouch by hand using Vicryl 2/0 sutures. RESULTS: Between November 2015 and February 2016, the study was performed on 10 patients. The average operating time for all cases was 75 min (range 63-87). There was no morbidity or mortality. No complications were observed, including band erosion and band infection. Operation costs were about $2000 lower with this method than with standard gastric bypass surgery. Postop the patients lost weight by 3-4 kg per month. CONCLUSION: Preliminary results show that laparoscopic band-separated one anastomosis gastric bypass have feasibility, safety, efficacy, and reduced operating costs. PMID- 27384683 TI - Immunodominant membrane proteins of phytoplasmas. AB - Phytoplasmas are plant-pathogenic, phloem-colonizing, cell wall-less microorganisms that are primarily dependent on insect transmission for their spread and survival. The life cycle of phytoplasmas involves replication in insects and host plants. Until recently, phytoplasmas have resisted all attempts at cultivation in cell-free media, making these pathogens poorly characterized on a physiological and biochemical basis. However, host-pathogen relationships can be studied by investigating immunodominant membrane proteins (IDPs), which are located on the exterior surfaces of phytoplasma cells and are the most abundant proteins of the cell membrane. These membrane proteins come in direct contact with both insect and plant hosts and are thought to play a crucial role in phytoplasma spread both within the plant and by insect vectors. Therefore, there is great interest in studying this class of proteins. We summarize and discuss important investigations about these membrane proteins, which have already provided a better understanding of the host-phytoplasma relationship. PMID- 27384684 TI - Physical Activity Behaviors and Influences Among Chinese-American Children Aged 9 13 Years: A Qualitative Study. AB - Low physical activity is a major health issue among Chinese Americans. This study explored Chinese-American children's physical activity behaviors and influencing factors. Twenty-five children of Chinese or Taiwanese descent were interviewed to understand their favorite sports or physical activities, physical activity environments, and influences on their physical activity. All were between the ages of 9 and 13. Interviews were transcribed and coded using thematic data analysis procedures. Major themes included: (1) team sports, particularly basketball, were commonly listed as favorite sports or activities; (2) physical activity occurred mostly at school or an after-school setting; and (3) family played a major role in physical activity. Some trends/differences were detected based on age, sex, and socioeconomic status. Interventions to promote physical activity among Chinese-American children should emphasize team sports and encourage physical activity in schools, but also explore ways to involves families outside of school. PMID- 27384685 TI - Stimulus frequency-dependent inhibition of micturition contractions of the urinary bladder by electrical stimulation of afferent Abeta, Adelta, and C fibers in cutaneous branches of the pudendal nerve. AB - We aimed to examine the afferent mechanisms for the reflex inhibition of the rhythmic micturition contractions (RMCs) of the urinary bladder induced by stimulation of the perineal skin afferents in urethane-anesthetized rats. Electrical stimulation (pulse duration: 0.5 ms) was applied to the cutaneous branches of the pudendal nerve (CBPN) at frequencies of 0.1, 1, and 10 Hz for 1 min. Nerve fiber groups were defined by recording compound action potentials from CBPN. Activation of only Abeta fibers (0.2 V) produced an inhibition of RMCs at 7 11 min after the onset of stimulation (late inhibition), at any tested frequency. Additional activation of Adelta fibers (1 V) produced additional early inhibition (immediately after stimulation) at 1 and 10 Hz. Furthermore, additional activation of C fibers (10 V) at 10 Hz completely stopped RMCs for >10 min. This strong inhibition persisted after local application of capsaicin to the stimulating CBPN. We conclude that activities of Abeta, Adelta, and C afferent fibers, without capsaicin-sensitive channels, can contribute to the inhibition of bladder contractions. PMID- 27384686 TI - Risk Factors for Developing Metabolic Acidosis after Radical Cystectomy and Ileal Neobladder. AB - PURPOSE: To investigate the serial changes of metabolic acidosis and identify associated risk factors in patients who underwent radical cystectomy and ileal neobladder. MATERIAL AND METHODS: From January 2010 to August 2014, 123 patients who underwent radical cystectomy and ileal neobladder reconstruction for bladder cancer were included in this study. Metabolic acidosis was defined as a serum bicarbonate level less than 22 mEq/L and impaired renal function was defined as a GFR <50ml/min. The presence of metabolic acidosis was evaluated at 1 month, 1 year, and 2 years after surgery. Multivariate logistic regression analysis was conducted to identify risk factors associated with development of metabolic acidosis. RESULTS: Metabolic acidosis was observed in 52%, 19.5%, and 7.3% of patients at 1 month, 1 year, and 2 years after surgery, respectively. At 1 month after surgery, impaired renal function was the only independent risk factor associated with metabolic acidosis (OR 3.87, P = 0.046). At 1 year after surgery, diabetes was the only independent risk factor associated with metabolic acidosis (OR 5.68, P = 0.002). At 2 years post-surgery, both age and diabetes were significant risk factors associated with metabolic acidosis. CONCLUSION: Approximately, half of patients experienced metabolic acidosis one month after ileal neobladder reconstruction. Preoperative impaired renal function was the most significant risk factor for developing metabolic acidosis in the early postoperative period. However, the incidence of metabolic acidosis decreased to less than 20% 1 year after surgery, and diabetes was an independent risk factor during this period. PMID- 27384687 TI - Management of Abnormal Placenta Implantation with Methotrexate: A Review of Published Data. AB - Abnormally invasive placenta is characterized by direct attachment of chorionic villi to the uterine wall. This adherent placenta traditionally has been managed by peripartum hysterectomy. Nowadays, there is a lot of interest toward gradual shift from traditional management of invasive placentation to conservative ones leaving the placenta in situ to avoid the surgical morbidity of hysterectomy and loss of future fertility. Administration of methotrexate (MTX), as an adjunctive antimetabolite drug, resulted in conflicting data during conservative management of abnormal placentation. This review assessed all published data on efficacy and safety of MTX therapy as conservative management of invasive placentation. Fifty three articles including one prospective cohort study, 2 retrospective cohort studies, 10 case series and 40 case reports were identified. Conservative management has beneficial effects on the avoidance of major surgery with the consequent morbidity and the preservation of future fertility. Infection and vaginal bleeding were main complications of MTX therapy. Although MTX therapy may result in accelerated involution or expulsion of placenta and has some beneficial effects on hemorrhagic events, but there is not enough evidence on its efficacy and safety to recommend its routine uses in all cases of invasive placenta. PMID- 27384688 TI - Comparison of Points of Departure for Health Risk Assessment Based on High Throughput Screening Data. AB - BACKGROUND: The National Research Council's vision for toxicity testing in the 21st century anticipates that points of departure (PODs) for establishing human exposure guidelines in future risk assessments will increasingly be based on in vitro high-throughput screening (HTS) data. OBJECTIVES: The aim of this study was to compare different PODs for HTS data. Specifically, benchmark doses (BMDs) were compared to the signal-to-noise crossover dose (SNCD), which has been suggested as the lowest dose applicable as a POD. METHODS: Hill models were fit to > 10,000 in vitro concentration-response curves, obtained for > 1,400 chemicals tested as part of the U.S. Tox21 Phase I effort. BMDs and lower confidence limits on the BMDs (BMDLs) corresponding to extra effects (i.e., changes in response relative to the maximum response) of 5%, 10%, 20%, 30%, and 40% were estimated for > 8,000 curves, along with BMDs and BMDLs corresponding to additional effects (i.e., absolute changes in response) of 5%, 10%, 15%, 20%, and 25%. The SNCD, defined as the dose where the ratio between the additional effect and the difference between the upper and lower bounds of the two-sided 90% confidence interval on absolute effect was 1, 0.67, and 0.5, respectively, was also calculated and compared with the BMDLs. RESULTS: The BMDL40, BMDL25, and BMDL18, defined in terms of extra effect, corresponded to the SNCD1.0, SNCD0.67, and SNCD0.5, respectively, at the median. Similarly, the BMDL25, BMDL17, and BMDL13, defined in terms of additional effect, corresponded to the SNCD1.0, SNCD0.67, and SNCD0.5, respectively, at the median. CONCLUSIONS: The SNCD may serve as a reference level that guides the determination of standardized BMDs for risk assessment based on HTS concentration response data. The SNCD may also have application as a POD for low-dose extrapolation. PMID- 27384689 TI - Corrado and colleagues reply to Van Brabandt and colleagues. PMID- 27384690 TI - Rare case of nephrocalcinosis in a 14-year-old girl: Questions. AB - A 14-year-old Caucasian girl with a history of primary hypoparathyroidism and unstable calcium and phosphorus levels and on ongoing treatment was admitted to the Department of Pediatric Nephrology because of the onset of nephrocalcinosis and difficulties achieving normocalcemia. Coexistence of hypoparathyroidism, oral candidiasis, dental enamel hypoplasia, and subclinical Hashimoto's disease was strongly suggestive for autoimmune polyglandular syndrome (APS) type I. One of the clinical implications of this diagnosis is the high probability of future occurrence of adrenal insufficiency and hence the importance of maintaining a high level of suspicion in case of the onset of symptoms like weakness, fainting, hypotonia, or hyperkaliemia. Addison's disease would, in fact, be quite challenging for the future management of this patient.This clinical quiz highlighted the importance of careful evaluation of all multiorgan symptoms occurring in a patient to prevent further complications. PMID- 27384691 TI - Pathogenesis of proteinuria in idiopathic minimal change disease: molecular mechanisms. AB - Minimal change disease (MCD) is the most common type of nephrotic syndrome in children and adolescents. The pathogenesis of proteinuria in this condition is currently being reassessed. Following the Shalhoub hypothesis, most efforts have been placed on identifying the putative circulating factor, but recent advancement in podocyte biology has focused attention on the molecular changes at the glomerular capillary wall, which could explain the mechanism of proteinuria in MCD. This report critically reviews current knowledge on the different postulated mechanisms at the glomerular capillary wall level for increased permeability to plasma proteins in MCD. The report helps describe the rationale behind novel therapies and suggests future targeted therapies for MCD. PMID- 27384692 TI - Rare case of nephrocalcinosis in a 14-year-old girl: Answers. PMID- 27384693 TI - Practitioners' Perceptions of the Soccer Extra-Time Period: Implications for Future Research. AB - Qualitative research investigating soccer practitioners' perceptions can allow researchers to create practical research investigations. The extra-time period of soccer is understudied compared to other areas of soccer research. Using an open ended online survey containing eleven main and nine sub questions, we gathered the perceptions of extra-time from 46 soccer practitioners, all working for different professional soccer clubs. Questions related to current practices, views on extra-time regulations, and ideas for future research. Using inductive content analysis, the following general dimensions were identified: 'importance of extra-time', 'rule changes', 'efficacy of extra-time hydro-nutritional provision', 'nutritional timing', 'future research directions', 'preparatory modulations' and 'recovery'. The majority of practitioners (63%) either agreed or strongly agreed that extra-time is an important period for determining success in knockout football match-play. When asked if a fourth substitution should be permitted in extra-time, 67% agreed. The use of hydro-nutritional strategies prior to extra-time was predominately considered important or very important. However; only 41% of practitioners felt that it was the most important time point for the use of nutritional products. A similar number of practitioners account (50%) and do not (50%) account for the potential of extra-time when training and preparing players and 89% of practitioners stated that extra-time influences recovery practices following matches. In the five minute break prior to extra time, the following practices (in order of priority) were advocated to players: hydration, energy provision, massage, and tactical preparations. Additionally, 87% of practitioners advocate a particular nutritional supplementation strategy prior to extra-time. In order of importance, practitioners see the following as future research areas: nutritional interventions, fatigue responses, acute injury risk, recovery modalities, training paradigms, injury epidemiology, and environmental considerations. This study presents novel insight into the practitioner perceptions of extra-time and provides information to readers about current applied practices and potential future research opportunities. PMID- 27384704 TI - The association of feeding behaviour with the resistance and tolerance to parasites in recently diverged sticklebacks. AB - Divergent natural selection regimes can contribute to adaptive population divergence, but can be sensitive to human-mediated environmental change. Nutrient loading of aquatic ecosystems, for example, might modify selection pressures by altering the abundance and distribution of resources and the prevalence and infectivity of parasites. Here, we used a mesocosm experiment to test for interactive effects of nutrient loading and parasitism on host condition and feeding ecology. Specifically, we investigated whether the common fish parasite Gyrodactylus sp. differentially affected recently diverged lake and stream ecotypes of three-spined stickleback (Gasterosteus aculeatus). We found that the stream ecotype had a higher resistance to Gyrodactylus sp. infections than the lake ecotype, and that both ecotypes experienced a cost of parasitism, indicated by negative relationships between parasite load and both stomach fullness and body condition. Overall, our results suggest that in the early stages of adaptive population divergence of hosts, parasites can affect host resistance, body condition and diet. PMID- 27384707 TI - Two Different Pathways in the Reduction of [(S=)PCl(MU-NtBu)]2 with Na. AB - Reduction of the cyclodiphosphazane [(S=)ClP(MU-NtBu)]2 (1) with sodium metal in refluxing toluene proceeds via two different pathways. One is a Wurtz-type pathway involving elimination of NaCl from 1 followed by head-to-tail cyclization to give the hexameric macrocycle [(MU-S)P(MU-NtBu)2 P(=S)]6 (2). The other pathway involves reduction of the P=S bonds of 1 to generate colorless singlet biradicaloid dianion trans-[S-P(Cl)(MU-NtBu)]2 (2-) , which is observed in the polymeric structures of three-dimensional [{(S-)ClP(MU-NtBu)2 PCl(S)}Na(Na?THF2 )]n (3) and two dimensional [{(S-)ClP(MU-NtBu)2 PCl(S)} (Na?THF)2 ]n (4). PMID- 27384708 TI - Thermostability Mechanism for the Hyperthermophilicity of Extremophile Cellulase TmCel12A: Implied from Molecular Dynamics Simulation. AB - Thermostability is of considerable importance for the application of cellulase in cellulosic ethanol production. The cellulase 12A from the hyperthermophile Thermotoga maritima (TmCel12A) is an ideal candidate to study thermostability of cellulases. Optimal temperature of the wild-type enzyme is 85 degrees C. Recently, it has been observed that surface loop mutation Y61G not only accelerates the hydrolysis rate but also extends the half-life of the enzyme at high temperature. However, the mechanism of how Y61G enhances thermostability of TmCel12A has not been revealed. Here, molecular dynamics simulation together with dynamic correlation network analysis was used to explore thermostability mechanism of TmCel12A. A hydrophobic cluster constructed by Y61, W176, V62, and L144 in the binding pocket was found to play a pivotal role in modulating thermostability as well as catalytic capability of TmCel12A. It stabilizes the apoenzyme at high temperature; however, it impedes the substrate binding. Y61G mutation disturbs the hydrophobic cluster as the counterpart amino acid W176 forms a cation-pi interaction with R60 instead of the pi-pi interaction with Y61 in WT. Moreover, Y61G mutation makes the enzyme more rigid and more extended via altering the amino acid communities at the hinge part of the enzyme. An earlier hypothesis proposed from crystallographic observation that Y61G may accelerate the products releasing has been also confirmed by our simulations. These findings may provide a new direction for both theoretical and experimental scientists to improve the thermostability of other cellulases that can be potentially applied in biofuel industry. PMID- 27384709 TI - Static and Dynamical Properties of heavy actinide Monopnictides of Lutetium. AB - In this work, density functional theory within the framework of generalized gradient approximation has been used to investigate the structural, elastic, mechanical, and phonon properties of lutetium monopnictides in rock-salt crystal structure. The spin orbit coupling and Hubbard-U corrections are included to correctly predict the essential properties of these compounds. The elastic constants, Young's modulus E, Poisson's ratio v, shear modulus G, anisotropy factor A and Pugh's ratio are computed. We found that all lutetium monopnictides are anisotropic and show brittle character. From the wave velocities along [100], [110] and [111] directions, melting temperature of lutetium monopnictides are predicted. Dynamical stability of these monopnictides has been studied by density functional perturbation theory. PMID- 27384705 TI - Extra-coding RNAs regulate neuronal DNA methylation dynamics. AB - Epigenetic mechanisms such as DNA methylation are essential regulators of the function and information storage capacity of neurons. DNA methylation is highly dynamic in the developing and adult brain, and is actively regulated by neuronal activity and behavioural experiences. However, it is presently unclear how methylation status at individual genes is targeted for modification. Here, we report that extra-coding RNAs (ecRNAs) interact with DNA methyltransferases and regulate neuronal DNA methylation. Expression of ecRNA species is associated with gene promoter hypomethylation, is altered by neuronal activity, and is overrepresented at genes involved in neuronal function. Knockdown of the Fos ecRNA locus results in gene hypermethylation and mRNA silencing, and hippocampal expression of Fos ecRNA is required for long-term fear memory formation in rats. These results suggest that ecRNAs are fundamental regulators of DNA methylation patterns in neuronal systems, and reveal a promising avenue for therapeutic targeting in neuropsychiatric disease states. PMID- 27384710 TI - Fluorodecarboxylation for the Synthesis of Trifluoromethyl Aryl Ethers. AB - The synthesis of mono-, di-, and trifluoromethyl aryl ethers by fluorodecarboxylation of the corresponding carboxylic acids is reported. AgF2 induces decarboxylation of aryloxydifluoroacetic acids, and AgF, either generated in situ or added separately, serves as a source of fluorine to generate the fluorodecarboxylation products. The addition of 2,6-difluoropyridine increased the reactivity of AgF2 , thereby increasing the range of functional groups and electronic properties of the aryl groups that are tolerated. The reaction conditions used for the formation of trifluoromethyl aryl ethers also served to form difluoromethyl and monofluoromethyl aryl ethers. PMID- 27384712 TI - Using Combined Diagnostic Test Results to Hindcast Trends of Infection from Cross Sectional Data. AB - Infectious disease surveillance is key to limiting the consequences from infectious pathogens and maintaining animal and public health. Following the detection of a disease outbreak, a response in proportion to the severity of the outbreak is required. It is thus critical to obtain accurate information concerning the origin of the outbreak and its forward trajectory. However, there is often a lack of situational awareness that may lead to over- or under reaction. There is a widening range of tests available for detecting pathogens, with typically different temporal characteristics, e.g. in terms of when peak test response occurs relative to time of exposure. We have developed a statistical framework that combines response level data from multiple diagnostic tests and is able to 'hindcast' (infer the historical trend of) an infectious disease epidemic. Assuming diagnostic test data from a cross-sectional sample of individuals infected with a pathogen during an outbreak, we use a Bayesian Markov Chain Monte Carlo (MCMC) approach to estimate time of exposure, and the overall epidemic trend in the population prior to the time of sampling. We evaluate the performance of this statistical framework on simulated data from epidemic trend curves and show that we can recover the parameter values of those trends. We also apply the framework to epidemic trend curves taken from two historical outbreaks: a bluetongue outbreak in cattle, and a whooping cough outbreak in humans. Together, these results show that hindcasting can estimate the time since infection for individuals and provide accurate estimates of epidemic trends, and can be used to distinguish whether an outbreak is increasing or past its peak. We conclude that if temporal characteristics of diagnostics are known, it is possible to recover epidemic trends of both human and animal pathogens from cross sectional data collected at a single point in time. PMID- 27384713 TI - Reliability and validity of the Finnish version of the Lower Extremity Functional Scale (LEFS). AB - PURPOSE: The present study aimed to assess the psychometric properties of the Finnish version of the Lower Extremity Functional Scale (LEFS) among foot and ankle patients. METHODS: The LEFS was translated and cross-culturally adapted to Finnish. We assessed the test-retest reliability, internal consistency, floor ceiling effect, construct validity and criterion validity in patients who underwent surgery due to musculoskeletal pathology of the foot and ankle (N = 166). RESULTS: The test-retest reliability was high (ICC = 0.93, 95% CI: 0.91 0.95). The standard error of measurement was 4.1 points. The Finnish LEFS showed high internal consistency (Cronbach's alpha = 0.96). A slight ceiling effect occurred as 17% achieved the maximum score. The LEFS correlation was strong with the 15D Mobility dimension (r = 0.74) and overall HRQoL (r = 0.66), pain during foot and ankle activity (r= -0.69) and stiffness (r= -0.62). LEFS correlated moderately with foot and ankle pain at rest (r= -0.50) and with physical activity (r = 0.46). CONCLUSIONS: The Finnish version of the LEFS showed reliability and validity comparable to those of the original version. This study indicates that the Finnish version of the LEFS serves both clinical and scientific purposes in assessing lower-limb function. Implications for Rehabilitation The Finnish version of the Lower Extremity Functional Scale (LEFS) is a reliable and valid tool for assessing lower-extremity musculoskeletal disability in Finnish-speaking population. Investigation of the psychometric properties of the Finnish version of the LEFS showed validity and reliability comparable to those of the original English version. The Finnish LEFS is easy to complete and suitable for clinical, rehabilitation and research purposes. PMID- 27384715 TI - Study of force loss due to friction comparing two ceramic brackets during sliding tooth movement. AB - OBJECTIVE: To compare the percentage of force loss generated during canine sliding movements in newly introduced ceramic brackets with metal brackets. MATERIALS AND METHODS: Two types of ceramic brackets, namely polycrystalline alumina (PCA) ceramic brackets (Clarity Advanced) and monocrystalline alumina (MCA) ceramic brackets (Inspire Ice) were compared with stainless steel (SS) brackets (Victory Series). All bracket groups (n = 5 each) were for the maxillary canines and had a 0.018-inch slot size. The brackets were mounted on an Orthodontic Measurement and Simulation System (OMSS) to simulate the canine retraction movement into the first premolar extraction space. Using elastic ligatures, 0.016 * 0.022" (0.40 * 0.56 mm) stainless steel archwires were ligated onto the brackets. Retraction force was applied via a nickel-titanium coil spring with a nearly constant force of approximately 1 N. The OMSS measured the percentage of force loss over the retraction path by referring to the difference between the applied retraction force and actual force acting on each bracket. Between group comparisons were done with one-way analysis of variance. RESULTS: The metal brackets revealed the lowest percentage of force loss due to friction, followed by the PCA and MCA ceramic bracket groups (67 +/- 4, 68 +/- 7, and 76 +/ 3 %, respectively). There was no significant difference between SS and PCA brackets (p = 0.97), but we did observe significant differences between metal and MCA brackets (p = 0.03) and between PCA and MCA ceramic brackets (p = 0.04). CONCLUSION: PCA ceramic brackets, whose slot surface is covered with an yttria stabilized zirconia-based coating exhibited frictional properties similar to those of metal brackets. Frictional resistance resulted in an over 60 % loss of the applied force due to the use of elastic ligatures. PMID- 27384714 TI - Current status and perspectives of Clonorchis sinensis and clonorchiasis: epidemiology, pathogenesis, omics, prevention and control. AB - Clonorchiasis, caused by Clonorchis sinensis (C. sinensis), is an important food borne parasitic disease and one of the most common zoonoses. Currently, it is estimated that more than 200 million people are at risk of C. sinensis infection, and over 15 million are infected worldwide. C. sinensis infection is closely related to cholangiocarcinoma (CCA), fibrosis and other human hepatobiliary diseases; thus, clonorchiasis is a serious public health problem in endemic areas. This article reviews the current knowledge regarding the epidemiology, disease burden and treatment of clonorchiasis as well as summarizes the techniques for detecting C. sinensis infection in humans and intermediate hosts and vaccine development against clonorchiasis. Newer data regarding the pathogenesis of clonorchiasis and the genome, transcriptome and secretome of C. sinensis are collected, thus providing perspectives for future studies. These advances in research will aid the development of innovative strategies for the prevention and control of clonorchiasis. PMID- 27384717 TI - Surgery Combined with Radiotherapy to Treat Spinal Tumors: A Review of Published Reports. AB - Spinal tumors result in high morbidity and a high rate of lower limb paralysis. Both surgical therapy and radiation therapy (RT) are used to treat spinal tumors; however, how best to combine these two therapies to maximize the benefits and minimize the risks is still being debated. It is also difficult to decide the optimal timing, course and dose of RT, especially in pregnant women and children. The aim of this review is to assist surgeons who are dealing with spinal tumors by providing comprehensive information about advanced techniques for administering RT with greater precision and safety, and about the impact of various ways of combining surgery and RT on therapeutic outcomes. We here review published reports about treating spinal tumors with a combination of these two forms of therapy and attempt to draw appropriate conclusions concerning selection of optimal treatment protocols. Our conclusion is that postoperative radiotherapy, especially with high-precision, low-dose and multiple fractions, and brachytherapy are promising therapies to combined with surgery. PMID- 27384716 TI - Tetramethylenedisulfotetramine: pest control gone awry. AB - Incidences of pesticide poisonings are a significant cause of morbidity and mortality worldwide. The seizure-inducing rodenticide tetramethylenedisulfotetramine is one of the most toxic of these agents. Although banned, it has been responsible for thousands of accidental, intentional, and mass poisonings in mainland China and elsewhere. An optimal regimen for treatment of poisoning has not been established. Its facile synthesis from easily obtained starting materials, extreme potency, and lack of odor, color, or taste make it a potential chemical threat agent. This review describes the toxicologic properties of this agent, more recent advances in our understanding of its properties, and recommendations for future research. PMID- 27384718 TI - Advances in Bone-targeted Drug Delivery Systems for Neoadjuvant Chemotherapy for Osteosarcoma. AB - Targeted therapy for osteosarcoma includes organ, cell and molecular biological targeting; of these, organ targeting is the most mature. Bone-targeted drug delivery systems are used to concentrate chemotherapeutic drugs in bone tissues, thus potentially resolving the problem of reaching the desired foci and minimizing the toxicity and adverse effects of neoadjuvant chemotherapy. Some progress has been made in bone-targeted drug delivery systems for treatment of osteosarcoma; however, most are still at an experimental stage and there is a long transitional period to clinical application. Therefore, determining how to combine new, polymolecular and multi-pathway targets is an important research aspect of designing new bone-targeted drug delivery systems in future studies. The purpose of this article was to review the status of research on targeted therapy for osteosarcoma and to summarize the progress made thus far in developing bone-targeted drug delivery systems for neoadjuvant chemotherapy for osteosarcoma with the aim of providing new ideas for highly effective therapeutic protocols with low toxicity for patients with osteosarcoma. PMID- 27384719 TI - Biological Reconstruction in Bone Sarcomas: Lessons from Three Decades of Experience. PMID- 27384720 TI - Delay in Diagnosis and Its Effect on Clinical Outcome in High-grade Sarcoma of Bone: A Referral Oncological Centre Study. AB - OBJECTIVE: To investigate delay in diagnosis by both patients and doctors, and to evaluate its effect on outcomes of high-grade sarcoma of bone in a single referral oncological center. METHODS: Fifty-four patients with osteosarcoma, 29 with Ewing sarcoma and 19 with chondrosarcoma were enrolled in this retrospective study. Delay in diagnosis was defined as the period between initial clinical symptoms and histopathological diagnosis at our center. The delays were categorized as patient- or doctor-related. Short total delays were defined as <4 months; prolonged delays >4 months were assumed to have prognostic relevance. RESULTS: Total delay in diagnosis was 688.0 days in patients with chondrosarcoma, which is significantly longer than the 163.3 days for osteosarcoma (P < 0.01) and 160.2 days for Ewing sarcoma (P < 0.01). Most doctor-related delays were at the pre-hospital stage, occurring at the general practitioner (GP)'s office. However, prolonged total delays (>=4 months) did not result in lower survival rates. Five year-overall survival rates were 67.0% for osteosarcoma, 49.0% for Ewing sarcoma and 60.9% for chondrosarcoma. Survival was significantly lower for patients with metastatic disease for all three types of sarcoma. CONCLUSION: Prolonged delay in diagnosis does not result in lower survival. Metastatic disease has a pronounced effect on survival. Aggressive tumor behavior results in shorter delays. Minimizing GP-related delays could be achieved by adopting a lower threshold for obtaining plain radiographs at the pre-hospital stage. PMID- 27384721 TI - Preliminary Application of Precision Genomic Medicine Detecting Gene Variation in Patients with Multifocal Osteosarcoma. AB - OBJECTIVES: The purpose of this study was to present our clinical experience of treating multifocal osteosarcoma (MFOS) in our center and gain more insight into the biology of this rare condition; in particular, to address with the help of precision genomic medicine the issue of whether the multiple osteosarcoma (OS) lesions in such patients are multi-centric or originate from one primary lesion and metastasize to other sites. Finally, we aimed to identify particular gene phenotypes and mutations that differentiate MFOS from OS with only one tumor. METHODS: Clinical data of patients with MFOS treated at our center between June 2007 and October 2014 were collected and analyzed retrospectively. High throughput sequencing of the whole exome of normal tissue and multiple lesions had been performed on samples from two patients (HJF and JZ) diagnosed in 2014. To explore the particular gene phenotype and clinical significance of MFOS, these sequencing results were analyzed and compared with those from patients with osteosarcoma in a single site. Seven patients with MFOS (three male and four female; average age 19.71 +/- 3.35 years were enrolled in this study. Two of these patients declined treatment and died after 4 and 6 months, respectively. The remaining patients received standard treatment comprising neoadjuvant chemotherapy, surgery and chemotherapy. The chemotherapy regimen was lobaplatin (45 mg/m(2) ), doxorubicin (60 mg/m(2) ) and ifosfamide (12 g/m(2) ). Patients were followed up every 3 months after completing treatment and evaluated by the Enneking and Response Evaluation Criteria in Solid Tumors scoring systems. RESULTS: Up to the last follow-up on 1 December 2015, three patients were still alive. The event-free survival ranged from 4 to 144 weeks (median, 50.14 weeks), the mean (+/-SD) being 55.45 +/- 45.47 weeks. Overall survival ranged from 16 to 388 weeks (median, 89 weeks; mean +/- SD, 118.7 +/- 147.7 weeks). The rates of mutation of the targeted drug-related genes were 133.5% +/- 3.0% in the proximal tibia lesion and 113.1% +/- 1.9% in the distal femur of patient HJF (P < 0.01) and 136.1% +/- 10.8% in the proximal tibial lesion and 122.3% +/- 5.5% in the proximal humerus of patient JZ (P = 0.0335). Furthermore, there were several anti oncogenes in the somatic copy number variation lists analyzed from the two patients, especially TP53. However, no kataegis was found. CONCLUSIONS: Early and radical surgery accompanied by appropriate chemotherapy is the optimal means of treating MFOS. These patients may benefit from precision genomic medicine. PMID- 27384722 TI - Impacts of Tumor Location, Nature and Bone Destruction of Extremity Osteosarcoma on Selection of Limb Salvage Operative Procedure. AB - OBJECTIVE: To study the impacts of tumor location, nature and extent of bone destruction on selection of operative protocol for extremity osteosarcoma (OS). METHODS: The medical records of 201 patients with extremity OS treated in our institute from December 1999 to June 2014 were retrospectively reviewed. Ninety eligible patients (56 males and 34 females) of average age 20 +/- 11 years (range, 4-40 years) were enrolled. Tumor locations were categorized as diaphyseal (4; diaphysis group) or juxta-articular (86); the latter being subclassified as with (51, type III, epiphysis group) or without invasion beyond the epiphyseal line or plate (35, type I and II, metaphysis group) according to MRI images. Tumor nature (osteogenic, 51; osteolytic, 39) was determined radiologically. Extent of bone destruction was quantitated according to Mirel's scoring system to obtain an "invasion score". Regular postoperative follow-up included physical examination and imaging evaluation. RESULTS: Fifty-four patients underwent biological reconstruction and 36 mechanical reconstruction. The mean follow-up duration was 51 months (range, 6-176 months, including four deaths within 12 months). Biological reconstruction was performed more frequently in the diaphysis and metaphysis groups (31/39, 79.5%) than mechanical reconstruction (8/39, 20.5%, P < 0.05). Biological reconstruction and articular preservation were associated with more satisfactory limb function (MSTS scores: 25.0 +/- 3.3 and 25.1 +/- 3.6) than mechanical reconstruction and articular resection (MSTS scores: 23.4 +/- 3.7 and 23.1 +/- 3.4, P < 0.05). Reconstruction methods and articular preservation had no relationship with overall or tumor-free survival (P > 0.05). Osteolytic lesions were associated with more extensive bone destruction than osteogenic lesions according to invasion scores (P < 0.05). Following biological reconstruction, high invasion scores (>8) had a 13.5-fold risk of fracture compared with low scores (<=8) (P < 0.05). Twenty-one subjects had recurrences, 30 metastases and 26 died. Postoperative complications included infection (6), fracture (10), and prosthesis loosening (4). Kaplan-Meier analysis indicated 5- and 10-year survival rates of 68.9% and 62.8%, respectively, and 5- and 10-year tumor-free survival rates of 66.7% and 57.8%, respectively. CONCLUSION: Selection of limb salvage operative protocol for extremity OS should rely on tumor location, nature and extent of bone destruction. Regardless of tumor site, mechanical reconstruction is indicated for tumors with high invasion scores (>8), whereas biological reconstruction is preferred for those with low invasion scores (<=8). Tumors sparing the epiphyseal line or plate are ideal candidates for articular preservation. PMID- 27384723 TI - Malignant Pelvic Tumors Involving the Sacrum: Surgical Approaches and Procedures Based on a New Classification. AB - OBJECTIVE: To introduce a new classification of Enneking type IV pelvic tumors involving the sacrum and a corresponding system of standardized surgical approaches and procedures for resection of such tumors, and to investigate the feasibility and therapeutic effect of the new system. METHODS: Data on 59 patients treated between February 2003 and February 2013 by standardized surgical approaches and procedures were retrospectively reviewed. The study subjects comprised 28 male and 31 female patients with a mean age at diagnosis of 36 years (range, 2-72 years). There are four subtypes in the new classification: (i) subtype IVa, neoplasms invading the ipsilateral sacral wing; (ii) subtype IVb, neoplasms invading the ipsilateral sacral foramina; (iii) subtype IVc, neoplasms invading the contralateral sacral foramina; and (iv) subtype IVd, neoplasms invading the whole of the sacrum. Standardized surgical approaches and procedures were devised for en-bloc resection for each subtype with adequate margins. RESULTS: Adequate margins were achieved in 43/59 patients (72.9%). The mean operation time was 5.0 h and the mean intraoperative blood loss 2157 mL. At the final follow-up, 27/53 patients (50.9%) who had been followed up were alive and in complete remission. The mean Musculoskeletal Tumor Society 93 score was 17.4 (58%) of a possible 30 points. The mean functional score for patients who had undergone a pelvic zone II resection was 15.2, compared with 19.0 for those with an intact pelvic zone II. CONCLUSIONS: The proposed standardized protocols should help orthopaedic surgeons to achieve adequate margins, manage risk, achieve better oncologic and functional outcomes, and minimize perioperative complications when treating massive pelvic tumors involving the sacrum. PMID- 27384724 TI - Surgical Treatment of Sacral Neurogenic Tumor: A 10-year Experience with 64 Cases. AB - OBJECTIVE: To explore the outcomes of surgical treatment of sacral neurogenic tumors METHODS: Between 1 January 2003 and 31 December 2012, data on 64 patients with sacral neurogenic tumors treated with surgery were retrospectively analyzed. The mean age of the 64 cases (35 males and 29 females) was 37.2 years (range, 21 69 years); 38 had neurilemmomas and 26 neurofibromas. Thirty-four of the tumors involved S 1 and S 2 , 11 S 3 or lower, and 19 were single presacral soft tissue masses. Tumors were removed via anterior, posterior or combined anteroposterior approaches. Patients with unstable sacroiliac joints underwent iliolumbar fixation. RESULTS: Depending on the extent of tumor involvement, one of three surgical approaches was used: a single anterior approach (19 patients), single posterior approach (25 patients), or a combined anteroposterior approach (20 patients). The mean operation time was 3 h (range, 2-6 h) and the mean blood loss 878 mL (range, 400-3120 mL). The mean duration of follow-up was 58.2 months (range, 24-93 months). These surgeries had the following complications. Three patients had massive intraoperative hemorrhage and posterior back pain and discomfort postoperatively. One patient had intraoperative ureteral injuries requiring intraoperative ureteral catheterization. In two patients, the tumor involved the S 1 nerve roots bilaterally, necessitating their removal, which resulted in obvious lower limb motion and sphincteric dysfunction. In 13 patients with unilateral tumor involvement of the nerve roots of S 1 and lower spinal levels, only the contralateral nerve roots of the S1 and lower levels were preserved; eight of these patients had impaired bladder and bowel function. Posterior incisions failed to heal in 10 patients, secondary wound healing occurred in nine of them and one required a gluteus maximus myocutaneous flap. Three patients developed postoperative cerebrospinal fluid leaks that were and alleviated by waist belt compression bandaging and placing them in the Trendelenburg position. Eight patients developed tumor recurrences postoperatively; pathological examination of the tissue excised in the second surgeries revealed malignant changes in the three patients with neurilemmomas. There were no intraoperative deaths. Rod fractures occurred in three of the 18 patients requiring iliolumbar reconstruction. CONCLUSIONS: The clinical characteristics of sacral neurogenic tumors make them easy to diagnose. The approach to resection should be determined by the location and size of the tumor. Patients with huge tumors may lose considerable blood intraoperatively and a have higher risk rate of postoperative complications. PMID- 27384725 TI - En Bloc Resection of Primary Malignant Bone Tumor in the Cervical Spine Based on 3-Dimensional Printing Technology. AB - OBJECTIVE: To investigate the feasibility and safety of en bloc resection of cervical primary malignant bone tumors by a combined anterior and posterior approach based on a three-dimensional (3-D) printing model. METHODS: Five patients with primary malignant bone tumors of the cervical spine underwent en bloc resection via a one-stage combined anteroposterior approach in our hospital from March 2013 to June 2014. They comprised three men and two women of mean age 47.2 years (range, 26-67 years). Three of the tumors were chondrosarcomas and two chordomas. Preoperative 3-D printing models were created by 3-D printing technology. Sagittal en bloc resections were planned based on these models and successfully performed. A 360 degrees reconstruction was performed by spinal instrumentation in all cases. Surgical margins, perioperative complications, local control rate and survival rate were assessed. RESULTS: All patients underwent en bloc excision via a combined posterior and anterior approach in one stage. Mean operative time and estimated blood loss were 465 minutes and 1290 mL, respectively. Mean follow-up was 21 months. Wide surgical margins were achieved in two patients and marginal resection in three; these three patients underwent postoperative adjuvant radiation therapy. One vertebral artery was ligated and sacrificed in each of three patients. Nerve root involved by tumor was sacrificed in three patients with preoperative upper extremity weakness. One patient (Case 3) had significant transient radiculopathy with paresis postoperatively. Another (Case 4) with C 4 and C 5 chordoma had respiratory difficulties and pneumonia after surgery postoperatively. He recovered completely after 2 weeks' management with a tracheotomy tube and antibiotics in the intensive care unit. No cerebrovascular complications and wound infection were observed. No local recurrence or instrumentation failure were detected during follow-up. CONCLUSION: Though technically challenging, it is feasible and safe to perform en bloc resection of cervical primary bone tumors. This is the most effective means of managing cervical spine tumors. Preoperative 3-D printing modelling enables better anatomical understanding of the relationship between the tumor and cervical spine and can assist in planning the surgical procedure. PMID- 27384726 TI - Transnasal Endoscopic Biopsy Approach to Atlas Tumor with X-ray Assisted and Related Radiographic Measure. AB - OBJECTIVE: To develop an endoscopic transnasal approach to atlas tumors and study its practicability. METHODS: This article comprises two components: an illustrative case report and observational data on 50 volunteers. As to the case report, a 34 year old man presented with occipital pain for more than 3 months and underwent systematic investigation in Qilu Hospital of Shandong University. CT and MRI scans showed bony destruction in the craniovertebral junction (CVJ) suggestive of tumor. Via an endoscopic transnasal approach to the suspected atlas tumor through the inferior nasal meatus, a Gallini biopsy needle was used to obtain tissue for examination. The procedure was performed endoscopically with double orientation X-ray guidance and coaxial technology after establishing the shortest distance for the biopsy track and range of target tissue and was assisted by manual palpation. As to the observational data, 50 volunteers underwent atlas-related morphometric image measurement using gemstone CT equipment. Biopsy track angles, range for biopsy of the atlas and biopsy track distances were measured by a blinded operator on CT images. RESULTS: CASE REPORT: pathological examination of the biopsy resulted in diagnosis of a chordoma. There were no complications such as bleeding, infection or spinal cord injury. One month later, the patient underwent tumor resection and reconstruction in other hospital and the diagnosis of chordoma was confirmed by pathological examination of the resected specimen. Observational data: measurements obtained from CT scans of the 50 volunteers were as follows. Biopsy track angles: mean leaning inside angle 3.53 degrees +/- 0.39 degrees and mean posterior slope angle 13.05 degrees +/- 1.39 degrees . Range for atlas biopsy: transverse diameter 11.84 +/- 1.24 mm and longitudinal diameter 9.67 +/- 0.90 mm. Biopsy track distances: from atlas to nostril, and to anterior and posterior edges of the inferior turbinate mucosa were 94.52 +/- 5.03 mm, 78.21 +/- 4.63 mm, and 33.51 +/- 3.13 mm, respectively. CONCLUSIONS: An endoscopic transnasal approach enables biopsy and diagnosis of tumors in the anterior arch of the atlas. Relevant measurements were obtained by assessing CT scans of 50 volunteers to assist operators to determine the effective and safe range for transnasal atlas biopsy. PMID- 27384727 TI - Functional Results and Emotional Acceptance after Scapulectomy for Malignant Shoulder Tumors. AB - OBJECTIVES: To demonstrate the functional results and emotional acceptance after scapulectomy for various malignant shoulder tumors. METHODS: Eight patients with malignant shoulder tumors who had undergone scapulectomy between April 2004 and March 2014 were retrospectively reviewed. They comprised seven men and one woman their mean age was 54 years (range, 24-69 years). All patients were diagnosed by pathological examination of biopsy specimens. The tumors were metastatic in four cases, having originated from a primary carcinoma of the liver in one patient, the lung in one patient and the kidney in two patients. The other four patients had primary malignant tumors in their scapulae, specifically, two scapular malignant fibrous histiocytomas, one scapular Ewing sarcoma and one soft tissue synovial sarcoma. The four patients with metastases were staged as III, and other four were staged as IIB. Six patients underwent total and two subtotal scapulectomy. The remaining soft tissues were sutured together directly in seven of the patients. The remaining patient, who had soft tissue synovial sarcoma, required transfer of a pedicle latissimus dorsi muscle flap. The functional results and emotional acceptance were evaluated by clinician using the Musculoskeletal Tumor Society (MSTS) scoring system. RESULTS: The average duration of follow-up was 22.8 months. Four patients were continuously disease free, three patients developed metastases and died of disease within 12 months of surgery and one patient with a scapular metastasis from the kidney survived with pulmonary nodules. No major complications, including infection or dislocation, occurred during or after surgery. The mean MSTS score was 16.3 (54%), which is similar to that previously reported in other studies of scapulectomy. There were no local tumor recurrences and only one patient developed pulmonary metastases. These outcomes are similar to those reported for scapular prostheses and there were fewer complications than in patients treated with allografts. The mean emotional acceptance score was 3.6 (72.5%). CONCLUSIONS: Performing scapulectomies on patients with malignant shoulder tumors without prostheses or allograft reconstruction achieves good functional results and emotional acceptance with a low rate of complications. PMID- 27384728 TI - Clinical and Radiographic Results of Reconstruction with Fibular Autograft for Distal Radius Giant Cell Tumor. AB - OBJECTIVE: To evaluate the result of en bloc resection and reconstruction of the distal radius with a non-vascularized fibular autograft for giant cell tumor (GCT) of bone. METHODS: Between 2005 and 2015, 12 eligible patients (seven males, five females, mean age 31.3 years) with grade III GCT of the distal radius were treated by en bloc resection and reconstruction with non-vascularized proximal fibular autografts in four Chinese institutions (members of Giant Cell Tumor Team of China). The patients had a clinical and radiographic review every 6 months for the first 2 years then annually thereafter. The functional, oncologic and radiological outcomes of the patients were analyzed. RESULTS: The mean duration of follow-up was 39.6 months. Bony union was achieved in all cases. None of the patients were dissatisfied with the shape and appearance of the wrist. The mean MSTS score was 25.23 +/- 2.38 (range, 22-29). The mean DASH score was 13.0 (range, 6.7-33.3). The average range of motion of the wrist was: 35.8 degrees +/ 14.5 degrees of extension, 14.0 degrees +/- 8.4 degrees of flexion, 15.5 degrees +/- 6.7 degrees of radial deviation, 19.4 degrees +/- 10.1 degrees of ulnar deviation, 57.2 degrees +/-18.9 degrees of pronation and 44.0 degrees +/ 24.8 degrees of supination. The average percentage of grip strength was 55.2% +/- 29.0% compared with that of the contralateral side. One localized soft tissue recurrence occurred; it was successfully managed by excision. Lung metastases developed postoperatively in one case and were treated by gamma knife radiotherapy. There was radiographic evidence of radiocarpal arthritis in eleven patients, bone resorption in ten, distal radioulnar joint diastasis in six, ulnar deviation of the wrist in seven, subluxation of the carpal bone in three and dislocation of the carpal bone in one patient. CONCLUSIONS: Reconstruction with a non-vascularized proximal fibular autograft is a reasonable option after en bloc resection of the distal radius for giant cell tumor of bone. PMID- 27384729 TI - Open Surgery for Osteoid Osteoma with Three Dimensional C-arm Scan under the Guidance of Computer Navigation. AB - OBJECTIVE: To evaluate the clinical outcomes of open surgery for osteoid osteoma with three-dimensional (3-D) C-arm scan under the guidance of computer navigation. METHODS: The clinical data of 14 patients who had undergone 3-D C-arm scan under the guidance of computer navigation during open surgery for osteoid osteoma from March 2012 to June 2015 were analyzed retrospectively. There were nine male and five female subjects aged from 9 to 55 years (mean, 26 years). Eight of the tumors were located in the femur, four in the tibia, one in the humerus and one in the scapula. Preoperative pain visual analogue scale (VAS) scores ranged from 2 to 6 (mean +/- SD, 4.7 +/- 1.1). Conventional surgical approaches were used to expose the tumor surfaces depending on their locations. Involved regions were scanned by 3-D C-arm fluoroscopy during the procedure and then the tumors were accurately located and their niduses removed under the guidance of computer navigation. Afterwards, repeat 3-D C-arm scans of the surgical region were performed to confirm tumor eradication. None of the patients received postoperative intravenous analgesia. Eight patients received oral non steroidal anti-inflammatory drugs on the day of surgery, these drugs being discontinued on the second postoperative day. Postoperative pathological diagnoses were recorded. At the follow-up visits, imaging and VAS scores were obtained to evaluate the therapeutic effect and any evidence of recurrence. RESULTS: All the patients successfully underwent computer navigation-guided surgery. The duration of surgery ranged from 60 to 135 min (mean, 94 min) and the amount of bleeding from 50 to 150 mL (mean, 80 mL). None of the patients needed bone grafting or internal fixation. No complications were seen. All patients were followed up for 4 to 36 months (mean, 16 months). Postoperative pathological diagnoses of osteoid osteoma were made in 12 patients; thus, the rate of pathologically confirmed diagnosis was 86%. VAS scores decrease to an average of 1.4 +/- 0.6 3 days after surgery and were zero for all patients 4 months after surgery. No tumor recurrence was found by X-ray or CT scan examination during follow-up. CONCLUSIONS: The niduses of osteoid osteomas can be eradicated by open surgery with 3-D C-arm scan under the guidance of computer navigation with minimal damage to bone structure and a high rate of pathologically confirmed diagnoses. PMID- 27384730 TI - Characterization of MicroRNA Expression Profiles in Patients with Giant Cell Tumor. AB - OBJECTIVE: Giant cell tumors of bone (GCTs) are bone destructive neoplasms, the bone resorption being mediated by osteoclasts. Given that microRNAs are crucially involved in tumorigenesis and the modulation of cell fate and behavior, they are promising candidates for regulation of osteoclastogenesis. However, no reliable miRNAs profile for GCT is available. Our study aimed to evaluate osteoclastogenesis-related miRNA expression in GCTs of Chinese patients. METHODS: From January 2013 to December 2014, 11 patients with GCTs were treated in our department and grouped into a GCT group. A control group comprising four patients with benign tumors of the iliac bone was established. The diagnoses were initially established by imaging examinations and intraoperative frozen sections and later confirmed by standard histologic examination. The GCT group (five male and six female patients) were aged from 17 to 61 years (mean, 32.9 years; SD, 12.8 years). Six patients with GCT underwent intralesional curettage surgery and the other five wide resection. According to Campanacci grading, four patients had Grade I tumors, three Grade II, and three Grade III. The average age of the control group was 28.75 years (SD, 14.24 years); all of them were diagnosed as having benign tumors and underwent iliac grafting. The morphology of the excised tissue was evaluated by examining standardized hematoxylin and eosin (HE) stained paraffin-embedded samples. In all, three osteoclastogenesis-related RNAs and 20 microRNAs (miRNAs) were extracted from the patients. The strength of expression was assessed by quantitative reverse transcription polymerase chain reaction (PCR ) and the results assessed by a Student's t test. RESULTS: Examination of HE stained sections revealed that the higher the Campanacci grade, the more numerous and bigger the osteoclasts (P < 0.05). PCR results indicated large amounts of osteoclast-related mRNA (cathepsin K, tartrate-resistant acid phosphatase and matrix metalloproteinase9) in GCTs (P < 0.05). Expression of six miRNAs was significantly weaker in the GCT than the control group (P < 0.05). The expression of has-mir-16-5p and has-let-7a-5p was correlated with Campanacci grade in the GCT patients (P = 0.009 and 0.034, respectively). The expression of these two miRNAs may indicate severity of bone destruction. CONCLUSION: Overall, the clinical utility of six novel miRNA markers for GCTs was demonstrated. Of these, strength of expression of hsa-mir-16-5p and hsa-let-7a-5p may indicate the grade of bone resorption. PMID- 27384731 TI - Expression of Matrix Metalloproteinase-9 and CD34 in Giant Cell Tumor of Bone. AB - OBJECTIVE: Giant cell tumor of bone (GCTB) invades extensively and metastasizes, however, the pathological grade and imaging findings are not accurate predictors of its prognosis. Thus, the aim of this study was to explore the relationships between expression of cluster of differentiation (CD)34 and matrix metalloproteinase-9 (MMP-9) and the biological behavior of GCTB with the hope of identifying predictors of prognosis. METHODS: Sixty-eight patients with GCTBs attending our institution from September 2008 to August 2013 were enrolled in this prospective study and grouped according to tumor location. Relevant patient characteristics were assessed. Additionally, the expression of CD34 and MMP-9 in these patients was assayed by an immunohistochemistry staining procedure and the relationships between CD34/MMP-9 and microvessel density (MVD) analyzed by Spearman correlation analysis. RESULTS: It was found that CD34 factor localizes in the cytoplasm of the endothelial cells of small blood vessels in the tumor stroma and is strongly expressed in GCTBs. In addition, radiological grading showed that there was significantly more CD34 antibody-labeled MVD in invasive than in non-invasive tumors (P < 0.05) and significantly more CD34 antibody labeled MVD in patients who developed recurrences than in those who did not (P < 0.05). Expression of MMP-9 was localized in the cytoplasm of tumor cells and the rate of MMP-9 positivity in GCTBs was significantly higher in active and invasive tumors than in non-invasive tumors (P < 0.01). Moreover, there were significantly more MVDs in MMP-9-positive than in MMP-9 negative tumors (P < 0.01). CD34 and MMP-9 are positively correlated with MVD values in GCTBs and closely correlated with their grade of malignancy. CONCLUSION: Expression of CD34 and MMP-9 accurately predicts clinical behavior detection and prognosis of GCTBs. PMID- 27384732 TI - Closed Suction Drainage Is Not Associated with Faster Recovery after Total Knee Arthroplasty: A Prospective Randomized Controlled Study of 80 Patients. AB - OBJECTIVE: To evaluate whether closed suction drainage (CSD) is associated with early recovery of knee function in patients undergoing total knee arthroplasty (TKA). METHODS: Between January 2015 and September 2015, 80 consecutive patients were prospectively randomized into two groups: a CSD group (40 cases; average age, 66.9 +/- 8.6 years; male, 8; female, 32) and a non-CSD group (40 cases; average age, 66.8 +/- 10.1 years; male, 9; female, 31). Local inflammation outcomes (assessed by a visual analog scale [VAS], swelling and skin temperature), calculated total blood loss (CBL), hidden blood loss (HBL), blood transfusion requirements and hemoglobin concentrations were recorded. Hospital for Special Surgery (HSS) knee scores, range of motion (ROM), limb swelling, tension vesicles, ecchymosis, time to regaining straight leg raising and duration of hospital stay were documented. All surgeries were performed by the same surgeon and followed up for 3 months. RESULTS: The peri-wound skin temperature and knee VAS pain scores were lower in the non-CSD group. Patients in the non-CSD group had significantly better knee ROM (P = 0.028). The time to regaining active straight leg raising was significantly shorter in the non-CSD groupN than in the CSD group (P = 0.014). In addition, patients in the non-CSD group had a shorter length of hospital stay (P = 0.004) than those in the CSD group, indicating earlier recovery of knee function. HBL was significantly less in the CSD group than the non-CSD group (P = 0.006) on postoperative day (POD) 5. However, CBL did not differ significantly between the two groups on POD5. There were no significant differences between two groups in all other assessed variables. CONCLUSION: In this randomized study, primary TKA without CSD was associated with faster recovery related to less local inflammation and better early knee function. Furthermore, use of a drain had no significant advantage with respect to other outcome measures and may have increased costs. Based on these data, CSD after primary TKA is not routinely indicated. PMID- 27384733 TI - Inhibition of Growth and Metastasis of Tumor in Nude Mice after Intraperitoneal Injection of Bevacizumab. AB - OBJECTIVE: To explore the inhibitory effect of bevacizumab, a vascular endothelial growth factor antibody, on angiogenesis in human osteosarcoma of nude mice. METHODS: Twenty-one nude mice were inoculated with red fluorescent protein (RFP)-labeled human osteosarcoma cell line 143B-RFP, that is, clones that expressed RFP in the cytoplasm, and randomly assigned to one of three groups: G1 (Control group, injected with saline solution); G2 (intraperitoneal bevacizumab 2 mg/kg twice per week) and G3 (intraperitoneal bevacizumab 5 mg/kg, twice per week). The tumor-bearing mice were examined in a fluorescence light box that was illuminated periodically. The primary tumors were measured by fluorescence imaging weekly and their volumes calculated. RESULTS: The mean tumor volumes were significantly smaller in the G3 (186.4 +/- 100.8 mm(3) ) than the control group (587.0 +/- 406.8 mm(3) ) (P < 0.05) on Day 31, and again significantly smaller in the G3 (677.3 +/- 461.9 mm(3) ) than the control group (3162.6 +/- 1529.2 mm(3) ) on Day 38 (P < 0.01). The average tumor volume in the G2 group was 493.5 +/- 425.4 mm(3) on Day 31 and 1870.1 +/- 1524.8 mm(3) on Day 38. The effect on tumor volume was greater in the G3 than the G2 group. Three mice in the G2 group, four in the G3 group and four in the control group developed lung metastases that were confirmed by pathological examination; these differences were not statistically significant (P < 0.05). CONCLUSIONS: Bevacizumab exhibits strong antiangiogenesis activity in experimental osteosarcoma in a nude mouse model but does not influence the incidence of lung metastasis. Our findings may have considerable potential for the treatment of osteosarcoma. PMID- 27384734 TI - Intervertebral Fusion with Mobile Microendoscopic Discectomy for Lumbar Degenerative Disc Disease. AB - The aim of this article is to introduce a technique for lumbar intervertebral fusion that incorporates mobile microendoscopic discectomy (MMED) for lumbar degenerative disc disease. Minimally invasive transforaminal lumbar interbody fusion is frequently performed to treat degenerative diseases of the lumbar spine; however, the scope of such surgery and vision is limited by what the naked eye can see through the expanding channel system. To expand the visual scope and reduce trauma, we perform lumbar intervertebral fusion with the aid of a MMED system that provides a wide field through freely tilting the surgical instrument and canals. We believe that this technique is a good option for treating lumbar degenerative disc disease that requires lumbar intervertebral fusion. PMID- 27384735 TI - Musculoskeletal Hydatid Cysts Resembling Tumors: A Report of Five Cases. AB - Although challenges in treatment of musculoskeletal hydatid cysts (HC) lesions have been documented, data regarding the musculoskeletal HC lesions resembling tumor is scarce. This paper presented 5 patients (3 males, 2 females) with a mean age of 41.6 years with tumor-like lesions of HC. Three of them had left ilium and acetabulum involvement, one involved left femur, and one involved left thigh muscle compartments. Pain was the main symptom and was seen in all patients. Clinical examination, radiologic evaluation, and histologic analysis were performed for diagnosis. Patients were treated through different surgical options, including simple debridement, bone cement filling with or without internal fixation, hip arthrodesis, reconstruction using hemipelvic replantation with femoral prosthesis and distal femur endoprosthetic replacement. After surgery, the operation region was washed by 20% hypertonic saline, and debridement was performed carefully without contamination. All patients received albendazole treatment. Cases were followed up 1 to 9 years for the recurrence. Walking difficulty and pain were the main symptoms during the follow-up. One patient was symptom-free. A reoccurrence in the perioperative soft tissue was detected in only one patient and control visits with antihelmintic treatment were recommended. We would like to emphasize that HC should be kept in mind for the differential diagnosis of the cystic or tumoral lesions of the musculoskeletal system, particularly in the endemic regions. Prompt diagnosis is of paramount importance for preventing destruction and complications. PMID- 27384736 TI - Limb Salvage by Distraction Osteogenesis for Distal Tibial Osteosarcoma in a Young Child: A Case Report. AB - Under the effective chemotherapy protocol, physeal distraction could be used as an effective limb salvage in the growing children with lower-limb malignant metaphyseal bone tumours and could actively prevent leg length discrepancy or malalignment that profoundly affects function. In this paper, we report a 7-year old boy with right distal tibial osteosarcoma but not yet invaded the epiphysis, which underwent surgical treatment after effective chemotherapy. The surgical procedure included two phases: epiphysiolysis (physeal distraction) and en-bloc resection of tumor and distraction osteogenesis. In the first phase, after osteotomy of the proximal fibula was performed, two Ilizarov rings were attached to the proximal tibia and one Ilizarov ring was applied to the distal tibia. At same time, U-shape ring as an important external fixator was been used in the axis of rotation of the ankle joint in order to balance the stress from the surrounding tissues, increase distracting stabilization and prevent the deformity or contracture of ankle joint. In the second phase, the tumor bone (5.7 cm) was en bloc resected by diaphyseal osteotomy. Distraction osteogenesis was commenced 1 week postoperatively at a rate of 1 mm twice a day. The patient was reviewed by X-ray intermittently. The new bone was formed and the entire bone defect was covered in four months after the operation. Doxorubicin and cisplatin as the neoadjuvant chemotherapy protocol are effective to osteosarcoma and chemotherapy process did not adversely affect the union. Through this technique, the right distal tibial epiphysis was reserved successfully. At the last follow-up, there are no local recurrence or metastasis and we achieve to prevent leg length discrepancy or malalignment that profoundly affects function. PMID- 27384737 TI - Application of Piezosurgery in Anterior Cervical Corpectomy and Fusion. AB - Anterior cervical corpectomy and fusion (ACCF) is frequently used to decompress the cervical spine; however, this procedure is risky when dealing with a hard disc or ossification of the posterior longitudinal ligament (OPLL). Piezosurgery offers a useful tool for performing this procedure. In this article, we present a 50 years old man who had cervical spondylotic myelopathy with OPLL at the C 6 level and segmental stenosis of the cervical spinal canal. When removing the posterior wall of his C 6 vertebral body and OPLL, piezosurgery was used to selectively cut hard structures piece by piece without injuring delicate soft tissues like the nerve roots and spinal cord. Because there is no bleeding from the bone surface with piezosurgery, it provides a clean operative field. PMID- 27384738 TI - ERRATUM. PMID- 27384739 TI - Which factors influence onset and latency to treatment in generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder? AB - Anxiety disorders are common, comorbid, and disabling conditions, often underdiagnosed and under-treated, typically with an early onset, chronic course, and prolonged duration of untreated illness. The present study aimed to explore the influence of sociodemographic and clinical factors in relation to onset and latency to treatment in patients with generalized anxiety disorder (GAD), panic disorder (PD), and obsessive-compulsive disorder (OCD). A total of 157 patients with a Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Text Revision (DSM-IV-TR) diagnosis of PD (n=49), GAD (n=68), and OCD (n=40) were recruited, and epidemiological and clinical variables were collected through a specific questionnaire. Statistical analyses were carried out to compare variables across diagnostic groups. PD, GAD, and OCD patients showed a duration of untreated illness of 53.9+/-81.5, 77.47+/-95.76, and 90.6+/-112.1 months, respectively. Significant differences between groups were found with respect to age, age of first diagnosis, age of first treatment, family history of psychiatric illness, onset-related stressful events, benzodiazepine prescription as first treatment, antidepressant prescription as first treatment, and help seeking (self-initiated vs. initiated by others). Patients with GAD, PD, and OCD showed significant differences in factors influencing onset and latency to treatment, which may, in turn, affect condition-related outcome and overall prognosis. Further studies with larger samples are warranted in the field. PMID- 27384740 TI - Pregnancy outcome in patients exposed to direct oral anticoagulants - and the challenge of event reporting. AB - Today, direct oral anticoagulants (DOAC) are widely used alternatives to Vitamin K antagonists (VKA). Women of reproductive age may become pregnant during anticoagulation and, while VKA carry an embryotoxic potential, the risk of DOAC embryopathy is unknown. As a result, some patients elect to terminate pregnancy for fear of DOAC embryotoxicity. To assess the risk of DOAC embryopathy, we reviewed cases of DOAC exposure in pregnancy collected from physicians, literature and pharmacovigilance systems of drug authorities and manufacturers. A total of 357 reports including duplicates were available from which 233 unique cases could be identified. Information on pregnancy outcome was available in only 137/233 cases (58.8 %): 67 live births (48.9 %); 31 miscarriages (22.6 %); 39 elective pregnancy terminations (28.5 %). In 93 cases (39.9 %) no outcome data were available (including 3 cases of ongoing pregnancy). Of the 137 pregnancies with reported outcomes, seven showed abnormalities (5.1 %) of which three (2.2 %) could potentially be interpreted as embryopathy: live birth with facial dysmorphism; miscarriage in week 10 with limb abnormality; elective pregnancy termination due to a foetal cardiac defect in a woman who had to terminate a previous pregnancy due to Fallot tetralogy. Within its limitations (small numbers, incomplete outcome data) our results do not indicate that DOAC exposure in pregnancy carries a high risk of embryopathy or that DOAC exposure per se should be used to direct patient counselling towards pregnancy termination. Pregnancy outcome data are inconsistently captured in pharmacovigilance databases indicating the strong need for a more robust system of reporting. PMID- 27384741 TI - A Modular Probe Strategy for Drug Localization, Target Identification and Target Occupancy Measurement on Single Cell Level. AB - Late stage failures of candidate drug molecules are frequently caused by off target effects or inefficient target engagement in vivo. In order to address these fundamental challenges in drug discovery, we developed a modular probe strategy based on bioorthogonal chemistry that enables the attachment of multiple reporters to the same probe in cell extracts and live cells. In a systematic evaluation, we identified the inverse electron demand Diels-Alder reaction between trans-cyclooctene labeled probe molecules and tetrazine-tagged reporters to be the most efficient bioorthogonal reaction for this strategy. Bioorthogonal biotinylation of the probe allows the identification of drug targets in a chemoproteomics competition binding assay using quantitative mass spectrometry. Attachment of a fluorescent reporter enables monitoring of spatial localization of probes as well as drug-target colocalization studies. Finally, direct target occupancy of unlabeled drugs can be determined at single cell resolution by competitive binding with fluorescently labeled probe molecules. The feasibility of the modular probe strategy is demonstrated with noncovalent PARP inhibitors. PMID- 27384744 TI - Stability and Oil Migration of Oil-in-Water Emulsions Emulsified by Phase Separating Biopolymer Mixtures. AB - Oil-in-water (O/W) emulsions with varying concentration of oil phase, medium chain triglyceride (MCT), were prepared using phase-separating gum arabic (GA)/sugar beet pectin (SBP) mixture as an emulsifier. Stability of the emulsions including emulsion phase separation, droplet size change, and oil migration were investigated by means of visual observation, droplet size analysis, oil partition analysis, backscattering of light, and interfacial tension measurement. It was found that in the emulsions prepared with 4.0% GA/1.0% SBP, when the concentration of MCT was greater than 2.0%, emulsion phase separation was not observed and the emulsions were stable with droplet size unchanged during storage. This result proves the emulsification ability of phase-separating biopolymer mixtures and their potential usage as emulsifiers to prepare O/W emulsion. However, when the concentration of MCT was equal or less than 2.0%, emulsion phase separation occurred after preparation resulting in an upper SBP rich phase and a lower GA-rich phase. The droplet size increased in the upper phase whereas decreased slightly in the lower phase with time, compared to the freshly prepared emulsions. During storage, the oil droplets exhibited a complex migration process: first moving to the SBP-rich phase, then to the GA-rich phase and finally gathering at the interface between the two phases. The mechanisms of the emulsion stability and oil migration in the phase-separated emulsions were discussed. PMID- 27384745 TI - Online restricted-access material combined with high-performance liquid chromatography and tandem mass spectrometry for the simultaneous determination of vanillin and its vanillic acid metabolite in human plasma. AB - An automated online solid-phase extraction with restricted-access material combined with high-performance liquid chromatography and tandem mass spectrometry was developed and validated for the simultaneous quantification of vanillin and its vanillic acid metabolite in human plasma. After protein precipitation by methanol, which contained the internal standards, the supernatant of plasma samples was injected to the system, the endogenous large molecules were flushed out, and target analytes were trapped and enriched on the adsorbent, resulting in a minimization of sample complexity and ion suppression effects. Calibration curves were linear over the concentrations of 5-1000 ng/mL for vanillin and 10 5000 ng/mL for vanillic acid with a coefficient of determination >0.999 for the determined compounds. The lower limits of quantification of vanillin and vanillic acid were 5.0 and 10.0 ng/mL, respectively. The intra- and inter-run precisions expressed as the relative standard deviation were 2.6-8.6 and 3.2-10.2%, respectively, and the accuracies expressed as the relative error were in the range of -6.1 to 7.3%. Extraction recoveries of analytes were between 89.5 and 97.4%. There was no notable matrix effect for any analyte concentration. The developed method was proved to be sensitive, repeatable, and accurate for the quantification of vanillin and its vanillic acid metabolite in human plasma. PMID- 27384746 TI - Significant Cooperativity Between Ruthenium and Silicon in Catalytic Transformations of an Isocyanide. AB - Complexes [PhBP3]RuH(eta(3)-H2SiRR') (RR' = Me,Ph, 1a; RR' = Ph2, 1b; RR' = Et2, 1c) react with XylNC to form carbene complexes [PhBP3]Ru(H)?[C(H)(N(Xyl)(eta(2)-H SiRR'))] (2a-c; previously reported for 2a,b). Reactions of 1a-c with XylNC were further investigated to assess how metal complexes with multiple M-H-Si bonds can mediate transformations of unsaturated substrates. Complex 2a eliminates an N methylsilacycloindoline product (3a) that results from hydrosilylation, hydrogenation, and benzylic C-H activation of XylNC. Turnover was achieved in a pseudocatalytic manner by careful control of the reaction conditions. Complex 1c mediates a catalytic isocyanide reductive coupling to furnish an alkene product (4) in a transformation that has precedent only in stoichiometric processes. The formations of 3a and 4 were investigated with deuterium labeling experiments, KIE and other kinetic studies, and by examining the reactivity of XylNC with an eta(3)-H2SiMeMes complex (1d) to form a C-H activated complex (6). Complex 6 serves as a model for an intermediate in the formation of 3a, and NMR investigations at -30 degrees C reveal that 6 forms via a carbene complex (1d) that isomerizes to aminomethyl complex 7d. These investigations reveal that the formations of 3a and 4 involve multiple 4-, 5-, and 6-coordinate silicon species with 0, 1, 2, or 3 Ru-H-Si bonds. These mechanisms demonstrate exceptionally intricate roles for silicon in transition-metal-catalyzed reactions with a silane reagent. PMID- 27384742 TI - Sex Differences in Hip Fracture Surgery: Preoperative Risk Factors for Delirium and Postoperative Outcomes. AB - OBJECTIVES: To describe the differences observed in risk factors for delirium and outcomes between men and women undergoing hip fracture repair surgery. DESIGN: Prospective cohort study. SETTING: Academic medical center. PARTICIPANTS: Individuals with acute hip fracture admitted to an academic medical center (N = 431). MEASUREMENTS: Information on preoperative demographic characteristics, medical history, laboratory results, and postoperative outcomes was obtained according to history and chart review. Delirium was assessed using the Confusion Assessment Method. RESULTS: The overall incidence of postoperative delirium was 34%, with men more likely to experience postoperative delirium (44.8%) than women (30.2%) (P = .004). Male sex was associated with postoperative delirium in individuals with hip fracture, even after adjusting for other preoperative risk factors. Other significant preoperative risk factors included age, dementia, Parkinson's disease, and American Society of Anesthesiologists classification. Men were also more likely to experience other postoperative complications and have longer hospital length of stay. CONCLUSION: Men are at higher risk of postoperative delirium after hip fracture repair than women and have more postoperative surgical complications. Their higher risk of postoperative delirium may be due to their underlying preoperative disease severity. PMID- 27384747 TI - Airflow-aligned helical nanofilament (B4) phase in topographic confinement. AB - We investigated a controlled helical nanofilament (HNF: B4) phase under topographic confinement with airflow that can induce a shear force and temperature gradient on the sample. The resulting orientation and ordering of the B4 phase in this combinational effort was directly investigated using microscopy. The structural freedom of the complex B7 phase, which is a higher temperature phase than the B4 phase, can result in relatively complex microscopic arrangements of HNFs compared with the B4 phase generated from the simple layer structure of the B2 phase. This interesting chiral/polar nanofilament behaviour offers new opportunities for further exploration of the exotic physical properties of the B4 phase. PMID- 27384748 TI - Performance of patient-reported outcomes in the assessment of rheumatoid arthritis disease activity:the experience of the ESPOIR cohort. AB - OBJECTIVES: Rheumatoid arthritis (RA) activity can be assessed by several outcome measures. The importance of patient-reported outcomes (PROs) has recently been advocated. Our objective was to determine whether patient self-assessment can reflect RA disease activity. METHODS: Data from patients included in the early arthritis ESPOIR cohort and fulfilling 2010 ACR/EULAR criteria for RA at month 12 were used. Data for several PROs (visual analogue scale for fatigue, pain, patient assessment of disease activity; Health Assessment Questionnaire [HAQ]; Medical Outcomes Study Short Form 36 [SF36]; Echelle de Mesure de l'Impact de la polyarthrite Rhumatoide-court [EMIR-court] and Routine Assessment of Patient Index Data 3 [RAPID3]) were collected and their association with disease activity measured by Disease Activity Score in 28 joints-3 variables (DAS28-3v) was assessed. The association of PROs and disease activity was assessed by explained variance, Pearson correlation and performance of each PRO in differentiating low versus high disease activity states. RESULTS: We evaluated data for 677 patients. Whatever the disease activity, less impaired PROs was associated with the lowest disease activity. All PROs were moderately correlated with RA disease activity. The RAPID3 had the best association with DAS28-3v in determining RA disease activity state (r=0.45-0.55, explained variance 30-45%, sensitivity 69-100% and specificity 55-78%). Global PROs (RAPID3, EMIR-court) had the highest association with disease activity, followed by PROs assessing physical function. CONCLUSIONS: The association of PROs and RA disease activity (DAS28-3v) remains moderate. RAPID3, a global PRO, had the best association with disease activity as compared with other analysed PROs. PMID- 27384749 TI - Genomic Impact of Neoadjuvant Therapy on Breast Cancer: Incomplete Response is Associated with Altered Diagnostic Gene Signatures. AB - PURPOSE: Neoadjuvant therapy (NAT) has been shown to clinically downstage locally advanced breast cancers. This study aimed to determine whether a meaningful change in gene signatures occurs between pre- and post-NAT breast cancers for patients who do not achieve a pathologic complete response. METHODS: The current analysis included women from the prospective Neoadjuvant Breast Registry Symphony Trial who had breast cancer and awaited NAT. MammaPrint and BluePrint (Agendia, Inc., Irvine, CA) assays were performed on pre- and post-NAT breast tumor samples. RESULTS: At the completion of NAT, 93 patients with residual disease had their remaining tumor analyzed for MammaPrint and BluePrint. Of 93 patients, 21 switched tumor classification: 16 from high risk (HR) to low risk (LR) and 1 from LR to HR (p < 0.001). Four additional patients switched molecular subtype but remained HR. Although only 17 patients switched in their MammaPrint risk classification, the underlying MPIndex was significantly altered after treatment across all patients (p < 0.001). Additionally, the three BluePrint indices for luminal, human epidermal growth factor receptor 2 (HER2), and basal type also were significantly altered after treatment, in a subtype-dependent manner. CONCLUSION: This substudy showed that NAT significantly altered the genomic signature of the patient's breast cancer compared with the patient's pretreatment genomic profile. These alterations occurred in a subtype-dependent manner, suggesting that NAT may have either eliminated the most susceptible tumor subclone, leaving the treatment resistant clone with a different genetic signature, or altered molecular characteristics of the original cancer. PMID- 27384750 TI - Aggressive Hemihepatectomy Combined with Resection and Reconstruction of Middle Hepatic Vein for Intrahepatic Cholangiocarcinoma. AB - BACKGROUND: Major hepatectomy for intrahepatic cholangiocarcinoma (ICC) sometimes involves resection of major hepatic veins, which might result in the future liver remnant (FLR) congestion. The necessity and efficacy of resection and reconstruction of the middle hepatic vein (MHV) during right or left hemihepatectomy for resection of ICC remains unclear. METHODS: Between 1995 and 2013, 68 patients underwent right (n = 24) or left hemihepatectomy (n = 44) for primary ICC, with (n = 27) or without (n = 41) resection of MHV. If the noncongested FLR volume was <40 % of the total liver volume, reconstruction of major hepatic veins was considered. RESULTS: No significant differences between the groups were observed for patients with or without resection of MHV in the pathologic findings, including negative surgical margins (81 vs. 85 %, P = 0.67) and overall survival (5-year survival rate: 18.3 vs. 33.4 %, P = 0.26). In five patients who underwent venous resection and reconstruction, the noncongested FLR increased from 37 to 74 % after reconstruction (P < 0.01); this noncongested FLR was almost similar to the patients without venous resection (72 %). Three patients undergoing venous resection without reconstruction developed postoperative hepatic failure (grade A in 2 and grade B in 1; International study group of liver surgery definition); however, there was no surgical mortality. CONCLUSIONS: Aggressive hemihepatectomy for ICC with venous resection in the FLR resulted in acceptable long-term outcome with no mortality when considering hepatic venous reconstruction based on our criterion. PMID- 27384751 TI - Yield of Staging Laparoscopy and Lavage Cytology for Radiologically Occult Peritoneal Carcinomatosis of Gastric Cancer. AB - BACKGROUND: This study aimed to identify the yield of staging laparoscopy with peritoneal lavage cytology for gastric cancer patients and to track it over time. METHODS: The medical records of patients with gastric or gastroesophageal adenocarcinoma who underwent pretreatment staging laparoscopy at the authors' institution from 1995 to 2012 were reviewed. The yield of laparoscopy was defined as the proportion of patients who had positive findings on laparoscopy, including those with macroscopic carcinomatosis, positive cytology, or other clinically important findings. To compare the yield of laparoscopy over time, the patients were divided into three 6-year ranges based on the date of diagnosis. Associations between clinicopathologic factors and peritoneal disease were examined using uni- and multivariate analyses. RESULTS: The study included 711 patients. Among these patients, 43.5 % had gastroesophageal junction tumors, 72.9 % had poorly differentiated adenocarcinoma, and 53 % had signet ring cell morphology. Endoscopic ultrasound had most commonly identified T3 (83.9 %) and N positive (66.4 %) tumors. At laparoscopy, 148 (20.8 %) patients had been found to have macroscopic peritoneal carcinomatosis. Among 514 macroscopically negative patients who underwent peritoneal lavage cytologic analysis, 68 (13.2 %) had positive cytology results for malignancy. The total laparoscopy yield was 36 %, which did not change over time (p = 0.58). Multivariate analysis demonstrated that positive cytology or carcinomatosis was associated with poorly differentiated histology, linitis plastica, and equivocal computed tomography findings. CONCLUSIONS: Laparoscopy remains a useful staging procedure to evaluate for peritoneal spread when treatment or surgery is considered, even with the current availability of high-quality imaging. PMID- 27384752 TI - Effectiveness of a freely available computerised cognitive behavioural therapy programme (MoodGYM) for depression: Meta-analysis. AB - OBJECTIVE: To investigate the effectiveness of a freely available computerised cognitive behavioural therapy programme (MoodGYM) for depression (primary outcome), anxiety and general psychological distress in adults. METHOD: We searched PsycINFO, CINAHL Plus, MEDLINE, EMBASE, Social Science Citation Index and references from identified papers. To assess MoodGYM's effectiveness, we conducted random effects meta-analysis of identified randomised controlled trials. RESULTS: Comparisons from 11 studies demonstrated MoodGYM's effectiveness for depression symptoms at post-intervention, with a small effect size ( g = 0.36, 95% confidence interval: 0.17-0.56; I2 = 78%). Removing the lowest quality studies ( k = 3) had minimal impact; however, adjusting for publication bias reduced the effect size to a non-significant level ( g = 0.17, 95% confidence interval: -0.01 to 0.38). Comparisons from six studies demonstrated MoodGYM's effectiveness for anxiety symptoms at post-intervention, with a medium effect size ( g = 0.57, 95% confidence interval: 0.20-0.94; I2 = 85%). Although comparisons from six studies did not yield significance for MoodGYM's effectiveness for general psychological distress symptoms, the small effect size approached significance ( g = 0.34, 95% confidence interval: -0.04 to 0.68; I2 = 79%). Both the type of setting (clinical vs non-clinical) and MoodGYM-developer authorship in randomised controlled trials had no meaningful influence on results; however, the results were confounded by the type of control deployed, level of clinician guidance, international region of trial and adherence to MoodGYM. CONCLUSIONS: The confounding influence of several variables, and presence of publication bias, means that the results of this meta-analysis should be interpreted with caution. Tentative support is provided for MoodGYM's effectiveness for symptoms of depression and general psychological distress. The programme's medium effect on anxiety symptoms demonstrates its utility for people with this difficulty. MoodGYM benefits from its free accessibility over the Internet, but adherence rates can be problematic and at the extreme can fall below 10%. We conclude that MoodGYM is best placed as a population-level intervention that is likely to benefit a sizeable minority of its users. PMID- 27384753 TI - Adaptive Resolution Simulations with Self-Adjusting High-Resolution Regions. AB - In adaptive resolution simulations, different regions of a simulation box are modeled with different levels of detail. Particles change their resolution on-the fly when traveling from one subregion to the other. This method is particularly useful for studying multiscale systems in which effects on a broad range of length and time scales play a role. Until now, the geometry of the high resolution region has been limited to simple geometries of spherical, cuboid, or cylindrical form, whose shape does not change during the simulation. However, many phenomena involve changes in size and shape of system components, for example, protein folding, polymer collapse, nucleation, and crystallization. In this work, we develop a scheme that uses a series of overlapping spheres to allow for an arbitrary division of space into domains of different levels of resolution. Furthermore, the geometry is automatically adjusted on-the-fly during the simulation according to changes in size and shape of, for example, a solvated macromolecule within the high-resolution region. The proposed approach is validated on liquid water. We then simulate the folding of an atomistically detailed polypeptide solvated in a shell of atomistic water that changes shape as the peptide conformation changes. We demonstrate that the peptide folding process is unperturbed by the use of our methodology. PMID- 27384754 TI - Thermodynamics of gaseous barium cerate studied by Knudsen effusion mass spectrometry. AB - RATIONALE: BaCeO3 species, which are known to be excellent proton conductors, are potential candidates as electrolytes in hydrogen concentrators and fuel cells. Oxides of barium and cerium, with their reactivity can, in turn, form gaseous associates - complex molecules with two different types of atoms (not including oxygen). To predict the possibility of the existence of gaseous associates formed by barium and cerium oxides it is important to know their thermodynamic characteristics. Until the present investigation, gaseous cerates were unknown. METHODS: High-temperature Knudsen effusion mass spectrometry was used to determine the partial pressures of vapor species over the BaO-CeO2 system, and the formation enthalpies of gaseous CeO2 and BaCeO3 were derived. Measurements of partial pressures and reaction enthalpies were performed with a MS-1301 mass spectrometer. Vaporization was carried out using molybdenum and tungsten effusion cells containing the samples under study and pure gold as a reference substance. A theoretical study of gaseous cerium dioxide and barium cerate was performed by several quantum chemical methods: DFT M06, DFT PBE0 and MP2. RESULTS: In the temperature range 1900-2120 K, CeO and CeO2 were found to be the main vapor species over the solid CeO2 . Ba, BaO, CeO, CeO2 and BaCeO3 species were found in the vapor over the BaO-CeO2 mixture. On the basis of the equilibrium constant of the gaseous reaction BaO + CeO2 = BaCeO3 , the standard formation enthalpy of gaseous BaCeO3 (-1065 +/- 25 kJ/mol) at 298 K was determined. Energetically favorable structures of gaseous CeO2 and BaCeO3 were found and vibrational frequencies were evaluated in the harmonic approximation. CONCLUSIONS: The stability of BaCeO3 gaseous species was confirmed by high-temperature mass spectrometry. Gas-phase reactions involving gaseous barium and cerium oxides with gaseous barium cerate were studied. The enthalpies of the formation reactions of gaseous barium cerate from gaseous BaO and CeO2 were evaluated theoretically and the obtained values were in agreement with the experimental ones. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27384756 TI - OH-Initiated Oxidation of m-Xylene on Black Carbon Aging. AB - Laboratory experiments are conducted to investigate aging of size-classified black carbon (BC) particles from OH-initiated oxidation of m-xylene. The variations in the particle size, mass, effective density, morphology, optical properties, hygroscopicity, and activation as cloud condensation nuclei (CCN) are simultaneously measured by a suite of aerosol instruments, when BC particles are exposed to the oxidation products of the OH-m-xylene reactions. The BC aging is governed by the coating thickness (Deltarve), which is correlated to the reaction time and initial concentrations of m-xylene and NOx. For an initial diameter of 100 nm and Deltarve = 44 nm, the particle size and mass increase by a factor of 1.5 and 10.4, respectively, and the effective density increases from 0.43 to 1.45 g cm(-3) due to organic coating and collapsing of the BC core. The BC particles are fully converted from a highly fractal to nearly spherical morphology for Deltarve = 30 nm. The scattering, absorption, and single scattering albedo of BC particles are enhanced accordingly with organic coating. The critical supersaturation for CCN activation is reduced to 0.1% with Deltarve = 44 nm. The results imply that the oxidation of m-xylene exhibits larger impacts in modifying the BC particle properties than those for the OH-initiated oxidation of isoprene and toluene. PMID- 27384755 TI - Using future thinking to reduce temporal discounting: Under what circumstances are the medial temporal lobes critical? AB - The capacity to envision the future plays an important role in many aspects of cognition, including our ability to make optimal, adaptive choices. Past work has shown that the medial temporal lobe (MTL) is necessary for decisions that draw on episodic future thinking. By contrast, little is known about the role of the MTL in decisions that draw on semantic future thinking. Accordingly, the present study investigated whether the MTL contributes to one form of decision making, namely intertemporal choice, when such decisions depend on semantic consideration of the future. In an intertemporal choice task, participants must select either a smaller amount of money that is available in the present or a larger amount of money that would be available at a future date. Amnesic individuals with MTL damage and healthy control participants performed such a task in which, prior to making a choice, they engaged in a semantic generation exercise, wherein they generated items that they would purchase with the future reward. In experiment 1, we found that, relative to a baseline condition involving standard intertemporal choice, healthy individuals were more inclined to select a larger, later reward over a smaller, present reward after engaging in semantic future thinking. By contrast, amnesic participants were paradoxically less inclined to wait for a future reward following semantic future thinking. This finding suggests that amnesics may have had difficulty "tagging" the generated item(s) as belonging to the future. Critically, experiment 2 showed that when the generated items were presented alongside the intertemporal choices, both controls and amnesic participants shifted to more patient choices. These findings suggest that the MTL is not needed for making optimal decisions that draw on semantic future thinking as long as scaffolding is provided to support accurate time tagging. Together, these findings stand to better clarify the role of the MTL in decision making. PMID- 27384757 TI - Nutrition and physical activity related school environment/policy factors and child obesity in China: a nationally representative study of 8573 students in 110 middle schools. AB - BACKGROUND: Obesity is a serious threat to global health. School is a key setting for obesity intervention. Research on school risk factors for child obesity is limited in developing countries. OBJECTIVES: To examine regional variations in obesity and school environments/policies and their associations among students in China. METHODS: Analyses were based on the first nationally representative sample of 8573 9th graders in 110 middle schools from 28 regions across China. Multilevel models tested associations between school factors and child self reported weight outcomes and by school urbanicity setting (urban, rural). RESULTS: Overweight/obesity rate is higher among boys and in urban areas. Schools in rural areas, or less developed regions, promote longer on-campus life, as is indicated by the presence of school cafeterias, night study sessions and longer class hours. Multilevel models show that (i) school cafeterias (OR = 2.53, 95% CI = 1.35-4.75) and internet bars close to school (OR = 1.63, 95% CI = 1.15-2.30) are associated with increased overweight/obesity risk in rural areas, especially for boys; (ii) school night study sessions are associated with lower overweight/obesity risk (OR = 0.69, 95% CI = 0.50-0.96) in rural areas. CONCLUSIONS: China has large regional disparities in school environment/policies related to nutrition and physical activity. Some school factors are associated with students' weight status, which vary across gender and areas. Future school based interventions should attend to diverse regional contexts. PMID- 27384758 TI - The Importance of Esophagography in Patients With Recessive Dystrophic Epidermolysis Bullosa. AB - OBJECTIVE: The purpose of this study was to assess esophageal damage in patients with recessive dystrophic epidermolysis bullosa (RDEB) with or without dysphagia. SUBJECTS AND METHODS: Fourteen patients with either severe generalized or another generalized form of RDEB recruited through a research and support foundation were evaluated for obstructive esophageal lesions by means of barium esophagography. RESULTS: All patients, even those without dysphagia, had at least one stenosis; five patients had two stenoses. Stenotic lesions occurred most often (74%) in the upper third of the esophagus. CONCLUSION: Esophageal stenosis is a common complication in patients with RDEB, even when they do not have dysphagia. We recommend regular esophagographic examinations of all patients with RDEB. PMID- 27384760 TI - Lymphocytopenia is associated with anti-Beta-2 glycoprotein-1 in patients with 220 systemic lupus erythematosus. AB - BACKGROUND: Anti B2-Glicoprotein 1 (B2-GPI) is an antiphospholipid antibody that may be present in primary or secondary antiphospholipid syndrome (APS). Systemic Lupus erythematosus (SLE) is the main disease associated with secondary APS. OBJECTIVE: To study the prevalence of anti B2-GPI in SLE patients. METHODS: Anti B2-GPI (IgM/IgG) was studied by ELISA in 88 patients with SLE of both genders; 18.6% of which with secondary APS. Charts were reviewed for clinical and serological profile. RESULTS: Anti B2-GPI was present in 18.6% of the whole sample and in 29.4% of those with secondary APS. At univariated analysis, the presence of anti B2-GPI was more common in patients with serositis (p=0.04), lymphocytopenia (p=0.003) and anti cardiolipin (aCl) IgM antibodies (p=0.04). In a logistic regression study, only the associations with lymphocytopenia (OR=8.2; 95%CI=2.1-39.3) and aCl IgM (p=0.04; OR=3.4; 95%CI=1.05-11.1) remained significant. CONCLUSION: There is a 18.6% prevalence of positive anti B2-GPI in SLE population that is associated with the presence of aCl IgM and lymphocytopenia. PMID- 27384759 TI - The Maternal Effect Genes UTX and JMJD3 Play Contrasting Roles in Mus musculus Preimplantation Embryo Development. AB - During the process of embryonic development in mammals, epigenetic modifications must be erased and reconstructed. In particular, the trimethylation of histone 3 lysine 27 (H3K27me3) is associated with gene-specific transcriptional repression and contributes to the maintenance of the pluripotent embryos. In this study, we determined that the global levels of the H3K27me3 marker were elevated in MII oocyte chromatin and decrease to minimal levels at the 8-cell and morula stages. When the blastocyst hatched, H3K27me3 was re-established in the inner cell mass. We also determined that H3K27me3-specific demethylases, UTX and JMJD3, were observed at high transcript and protein levels in mouse preimplantation embryos. In the activated oocytes, when the H3K27me3 disappeared at the 8-cell stage, the UTX (but not JMJD3) protein levels were undetectable. Using RNA interference, we suppressed UTX and JMJD3 gene expression in the embryos and determined that the functions of UTX and JMJD3 were complementary. When JMJD3 levels were decreased by RNA interference, the embryo development rate and quality were improved, but the knockdown of UTX produced the opposite results. Understanding the epigenetic mechanisms controlling preimplantation development is critical to comprehending the basis of embryonic development and to devise methods and approaches to treat infertility. PMID- 27384761 TI - Erratum to: Effect of VKORC1, CYP2C9, CYP4F2, and GGCX Gene Polymorphisms on Warfarin Dose in Japanese Pediatric Patients. PMID- 27384763 TI - Correction: New Insight into Metal Ion-Driven Catalysis of Nucleic Acids by Influenza PA-Nter. AB - [This corrects the article DOI: 10.1371/journal.pone.0156972.]. PMID- 27384762 TI - The Potential of Food Fortification to Add Micronutrients in Young Children and Women of Reproductive Age - Findings from a Cross-Sectional Survey in Abidjan, Cote d'Ivoire. AB - Poor micronutrient intakes are a major contributing factor to the high burden of micronutrient deficiencies in Cote d'Ivoire. Large-scale food fortification is considered a cost-effective approach to deliver micronutrients, and fortification of salt (iodine), wheat flour (iron and folic acid), and vegetable oil (vitamin A) is mandatory in Cote d'Ivoire. A cross-sectional survey on households with at least one child 6-23 months was conducted to update coverage figures with adequately fortified food vehicles in Abidjan, the capital of and largest urban community in Cote d'Ivoire, and to evaluate whether additional iron and vitamin A intake is sufficient to bear the potential to reduce micronutrient malnutrition. Information on demographics and food consumption was collected, along with samples of salt and oil. Wheat flour was sampled from bakeries and retailers residing in the selected clusters. In Abidjan, 86% and 97% of salt and vegetable oil samples, respectively, were adequately fortified, while only 32% of wheat flour samples were adequately fortified, but all samples contained some added iron. There were no major differences in additional vitamin A and iron intake between poor and non-poor households. For vitamin A in oil, the additional percentage of the recommended nutrient intake was 27% and 40% for children 6-23 months and women of reproductive age, respectively, while for iron from wheat flour, only 13% and 19% could be covered. Compared to previous estimates, coverage has remained stable for salt and wheat flour, but improved for vegetable oil. Fortification of vegetable oil clearly provides a meaningful additional amount of vitamin A. This is not currently the case for iron, due to the low fortification levels. Iron levels in wheat flour should be increased and monitored, and additional vehicles should be explored to add iron to the Ivorian diet. PMID- 27384764 TI - Ion channel blockers and glioblastoma risk and outcome: a nested case-control and retrospective cohort studies. AB - PURPOSE: Mutations in ion channels are common among patients with glioblastoma multiforme (GBM) and promote cell migration and invasion. We sought to evaluate the association between the use of specific ion channel blockers such as digoxin, amiodarone, diltiazem and verapamil and GBM risk and survival. METHODS: We conducted a nested case-control study in a large primary care database from the UK. Cases were defined as all individuals with incident diagnosis of GBM during follow-up. For each case, up to four controls were selected using incidence density sampling. The primary exposure of interest was active treatment with each of the four ion channel blockers. We used conditional logistic regression to estimate odds ratios and 95% confidence interval (CI) for the association between ion channel blocker use and GBM risk. We then performed a Cox regression analysis among those diagnosed with GBM in order to evaluate the association between use of ion channel blockers and overall survival. Both analyses were adjusted to common confounders. RESULTS: The study included 1076 cases and 4253 matched controls. There was no statistically significant difference between cases and controls in cardiac and metabolic risk factors. There was no change in GBM risk in active users of ion channel blockers compared with non-users. Among patients with GBM, active users of amiodarone had worse survival compared with never users with an HR of 4.41 (95%CI 1.95-9.96). There was no statistically significant change in survival among diltiazem, verapamil or digoxin users. CONCLUSION: Treatment with specific ion channel blockers was not associated with the risk of GBM but was associated with worse survival in patients with GBM. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27384765 TI - Association of Epidermolysis Bullosa Simplex With Mottled Pigmentation and EXPH5 Mutations. AB - Importance: Epidermolysis bullosa simplex (EBS) is a group of clinically and genetically diverse mechanobullous genodermatoses characterized by the fragility of skin and mucous membranes. Recently, mutations in EXPH5 encoding exophilin-5 (also known as Slac2-b, an effector protein involved in intracellular vesicle trafficking and exosome secretion) have been implicated in the pathophysiology of EBS. Herein, we report a novel homozygous nonsense mutation in EXPH5 responsible for an EBS subtype with mottled pigmentation. Objective: To identify the gene mutation(s) accountable for the mottled pigmentation phenotype in a patient with suspected inherited skin fragility disorder. Design, Setting, and Participant: Data for this case report were acquired in an outpatient clinic and concern a referral from the primary care physician to the national Center for Blistering Diseases in The Netherlands. Data were acquired and analyzed from 2014 to 2016. Main Outcomes and Measures: Clinical examination and investigation were performed of the molecular basis of patient's skin fragility and mottled pigmentation phenotype. Electron microscopy studies described the underlying abnormalities on an ultrastructural level. Results: The clinical phenotype is characterized by mild generalized skin fragility, trauma-induced skin blistering since infancy, and development of remarkable diffuse mottled pigmentation on the trunk and proximal extremities. Sequencing the complete set of genes associated with epidermolysis bullosa revealed a homozygous nonsense mutation in exon 6 of EXPH5: c.3917C>G, p.Ser1306*. Electron microscopy revealed disruption of keratin filament cytoskeleton and accumulation of melanosomes in a disordered distribution in the keratinocytes. Conclusions and Relevance: To our knowledge, the current study illustrates the first clinically well-documented, mottled pigmentation phenotype related to a novel EXPH5 mutation. In addition, by means of electron microscopy image analysis, it proposes a hypothesis for the pigmentary changes in this rare autosomal recessive EBS subtype. These findings expand the genetic and phenotypic spectrum of human inherited skin fragility disorders, and we propose the addition of EBS resulting from EXPH5 mutations to the EBS-mottled pigmentation subtype. PMID- 27384766 TI - Efficacy and safety in pharmacological cardioversion of recent-onset atrial fibrillation: a propensity score matching to compare amiodarone vs class IC antiarrhythmic drugs. AB - The acute management of recent-onset (<48 h) atrial fibrillation (AF) is still debated. Aim of our study was to compare efficacy and safety of intravenously administered class IC antidysrhythmic agents vs amiodarone in a propensity score matched series of patients acutely treated for AF in the emergency department. During a 3-year period, we retrospectively evaluated all episodes of recent-onset (<48 h) AF pharmacologically treated for sinus rhythm restoration in the emergency department. By means of a propensity score matching considering the main statistically different covariates, we selected two accurately matched treatment groups. We analysed the differences between amiodarone and class IC group in terms of efficacy and safety that is conversion to sinus rhythm rates within 12 and 48 h after starting treatment, time to conversion, and adverse drug effects. An overall number of 817 episodes of recent-onset AF were collected (amiodarone group = 406, class IC group = 411). After matching, we obtained 358 episodes equally divided (amiodarone group = 179 and class IC group = 179). Conversion rates within 12 h were 139 (53.1 %) in amiodarone group and 95 (72.6 %) in class IC group (p < 0.05). Median time for cardioversion was 420 min (331.6 508.3 CI 95 %) in amiodarone and 55 min (44.9-65.1 CI 95 %) in class IC group (p < 0.05). The incidence of adverse events in both groups was very low and equally distributed (p = ns). Intravenously administration of class IC agents, when compared with amiodarone, proved to be more rapid and effective, and equally safe in the acute management of recent-onset AF. PMID- 27384767 TI - Older adults in Emergency Departments: the challenge of undertriage. PMID- 27384768 TI - Developmental defect of cytochrome oxidase mutants of Streptomyces coelicolor A3(2). AB - To study the link between energy metabolism and secondary metabolism/morphological development in Streptomyces, knockout mutants were generated with regard to the subunits of the cytochrome oxidase supercomplex (CcO) in Streptomyces coelicolor A3(2). All mutants exhibited an identical phenotype: viable but defective in antibiotic production and cell differentiation when grown in both complex and minimal media. The growth yield of the CcO mutant was about half of that of the WT strain on glucose medium while both strains grew similarly on maltose medium. Intracellular ATP measurement demonstrated that the CcO mutant exhibited high intracellular ATP level. A similar elevation of intracellular ATP level was observed with regard to the WT strain cultured in the presence of BCDA, a copper-chelating agent. Reverse transcriptase PCR analysis demonstrated that the transcription of ATP synthase operon is upregulated in the CcO mutant. Addition of carbonylcyanide m-chlorophenylhydrazone, an inhibitor of ATP synthesis, promoted antibiotic production and aerial mycelia formation in the CcO mutant and BCDA-treated WT cells. We hypothesize that the deficiency of CcO causes accumulation of intracellular ATP, and that the high ATP level inhibits the onset of development in S. coelicolor. PMID- 27384769 TI - Serum Proteomics Analysis in Rats of Immunosuppression Induced by Chronic Stress. AB - The immune system can be damaged by chronic stress. However, for this process, the involved molecular alterations and their regulatory roles played in immunosuppression still remain unclear. This study was aimed to identify the differences in serum protein expressions that are closely associated with the effect of chronic stress on immune function. Serum protein levels of rats in control group and chronic stress group were measured by iTRAQ analysis. Subsequently, among the 121 differentially expressed proteins screened between the two groups, 46 proteins were upregulated (>1.5-fold, P < 0.05), while 75 proteins were downregulated (<0.67-fold, P < 0.05). Bioinformatics analysis revealed that most of the differentially expressed proteins were in relation with the metabolic, cellular, response stimulus and immune system processes. The significantly differential expression of ceruloplasmin, haptoglobin, catalase and peroxiredoxin-1 were picked out for reconfirmation by ELISA analysis. The results were consistent with those obtained by iTRAQ. What is more, the roles of above mentioned four proteins, apolipoprotein B-100 and heat-shock protein 90 in immunosuppression induced by chronic stress were discussed. Taken together, these findings may provide a new insight into better understanding the molecular mechanisms of immunosuppression induced by chronic stress. PMID- 27384770 TI - A Framework to Account for Sedimentation and Diffusion in Particle-Cell Interactions. AB - In vitro experiments provide a solid basis for understanding the interactions between particles and biological systems. An important confounding variable for these studies is the difference between the amount of particles administered and that which reaches the surface of cells. Here, we engineer a hydrogel-based nanoparticle system and combine in situ characterization techniques, 3D-printed cell cultures, and computational modeling to evaluate and study particle-cell interactions of advanced particle systems. The framework presented demonstrates how sedimentation and diffusion can explain differences in particle-cell association, and provides a means to account for these effects. Finally, using in silico modeling, we predict the proportion of particles that reaches the cell surface using common experimental conditions for a wide range of inorganic and organic micro- and nanoparticles. This work can assist in the understanding and control of sedimentation and diffusion when investigating cellular interactions of engineered particles. PMID- 27384771 TI - Stem Cell Therapy and Administration Routes After Stroke. AB - Cell-based therapy has demonstrated safety and efficacy in experimental animal models of stroke, as well as safety in stroke patients. However, various questions remain regarding the therapeutic window, dosage, route of administration, and the most appropriate cell type and source, as well as mechanisms of action and immune-modulation to optimize treatment based on stem cell therapy. Various delivery routes have been used in experimental stroke models, including intracerebral, intraventricular, subarachnoid, intra-arterial, intraperitoneal, intravenous, and intranasal routes. From a clinical point of view, it is necessary to demonstrate which is the most feasible, safest, and most effective for use with stroke patients. Therefore, further experimental studies concerning the safety, efficacy, and mechanisms of action involved in these therapeutic effects are required to determine their optimal clinical use. PMID- 27384773 TI - Emotional Detachment of Partners and the Sanctity of the Relationship with the Analyst as the Most Powerful Curative Factor. AB - The relationship between partners and the analyst is considered the most basic means for healing in contemporary psychoanalytic theories and analyses. It also holds as one of the most fundamental phenomenon's of psychoanalysis, so it comes as no surprise that it has always been deliberated over as an object of great interest as well as immense controversy. This same relationship, mutually co created by the analyst and each individual and partner in analysis, represents also the core of sanctity and sacred space in contemporary psychoanalysis. PMID- 27384772 TI - Association of Hypoxia-Inducible Factor-2 Alpha Gene Polymorphisms with the Risk of Hepatitis B Virus-Related Liver Disease in Guangxi Chinese: A Case-Control Study. AB - OBJECTIVE: Hypoxia-inducible factor-2 alpha (HIF-2a) plays a major role in the progression of disease, although the role of HIF-2alpha gene polymorphisms in hepatitis B virus (HBV)-related diseases remains elusive. The aim of this study is to determine whether HIF-2a rs13419896 and rs6715787 single-nucleotide polymorphisms (SNPs) are associated with susceptibility to chronic hepatitis B (CHB), liver cirrhosis (LC), or hepatocellular carcinoma (HCC). METHOD: A case control study of 107 patients with CHB, 83 patients with LC, 234 patients with HCC, and 224 healthy control subjects was carried out, and the HIF-2a rs13419896 and rs6715787 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: No significant differences were observed in the genotype or allele frequency of two HIF-2a SNPs between the cases and controls (all p>0.05). However, in subgroup analysis by gender, the HIF-2a rs13419896 GA and AA genotypes were significantly associated with a risk of CHB (odds ratio [OR] = 3.565, 95% confidence interval [CI] = 1.123-11.314, p = 0.031 and OR = 12.506, 95% CI = 1.329-117.716, p = 0.027) in females, and the A allele of rs13419896 was associated with a risk of CHB (OR = 2.624, 95% CI = 1.244 5.537, p = 0.011) and LC (OR = 2.351, 95% CI = 1.002-5.518, p = 0.050) in females. The rs6715787 CG genotype polymorphism may contribute to a reduced risk of LC in the Guangxi Zhuang Chinese population (OR = 0.152, 95% CI = 0.028-0.807, p = 0.027), as determined via subgroup analysis by ethnicity. Moreover, binary logistic regression analyses that were adjusted by drinking status indicated that the AA genotype of rs13419896 may contribute to an increased risk of LC in the non-alcohol-drinking population (OR = 3.124, 95% CI = 1.091-8.947, p = 0.034). In haplotype analysis, GG haplotype was significantly associated with a reduced risk of LC (OR = 0.601, 95% CI = 0.419-0.862, p = 0.005). CONCLUSIONS: The HIF-2a rs13419896 polymorphism is associated with an increased risk of CHB and LC in the Guangxi Chinese population, especially in females and in the non-alcohol-drinking population, while the HIF-2a gene rs6715787 polymorphism is associated with a decreased risk of LC in the Guangxi Zhuang population. PMID- 27384774 TI - Sequence-Specific Recognition of DNA by Proteins: Binding Motifs Discovered Using a Novel Statistical/Computational Analysis. AB - Decades of intensive experimental studies of the recognition of DNA sequences by proteins have provided us with a view of a diverse and complicated world in which few to no features are shared between individual DNA-binding protein families. The originally conceived direct readout of DNA residue sequences by amino acid side chains offers very limited capacity for sequence recognition, while the effects of the dynamic properties of the interacting partners remain difficult to quantify and almost impossible to generalise. In this work we investigated the energetic characteristics of all DNA residue-amino acid side chain combinations in the conformations found at the interaction interface in a very large set of protein-DNA complexes by the means of empirical potential-based calculations. General specificity-defining criteria were derived and utilised to look beyond the binding motifs considered in previous studies. Linking energetic favourability to the observed geometrical preferences, our approach reveals several additional amino acid motifs which can distinguish between individual DNA bases. Our results remained valid in environments with various dielectric properties. PMID- 27384775 TI - Perinatal Advantages and Disadvantages of Being Underweight before Pregnancy: A Population-Based Study. AB - AIMS: To evaluate the advantages and disadvantages of being underweight before pregnancy. METHODS: Cohort study of a large population-based dataset of singleton births was used to compare maternal and neonatal outcomes of pre-gravid underweight body mass index (BMI <18.5 kg/m2) women with pre-gravid normal weight controls (BMI 18.5-24.9 kg/m2). RESULTS: A total of 10,995 pre-gravid underweight and 146,155 pre-gravid normal weight mothers were compared. The mean maternal age and gestational age were not different but lean mothers were significantly and more frequently primiparous, had a higher incidence of births at <36 and <32 weeks' gestation, and had a significantly higher incidence of low and very low birth weight infants. Lean mothers had a significantly lower incidence of birth weights >4,000 g, less cesarean births and a lower incidence of gestational diabetes and hypertensive disorders. CONCLUSIONS: A tradeoff exists between the advantages of being lean before pregnancy in terms of less maternal morbidity in return for gaining a more advanced gestational age and higher birth weight. PMID- 27384776 TI - Lateral lumbar vertebral body screw predisposes to neuralgia after limb-salvage surgery for pelvic tumors: a single-center, retrospective study of 349 cases. AB - PURPOSE: To investigate the incidence and risk factors of neuralgia after limb salvage surgery for pelvic tumors with focus on the reconstruction methods. METHODS: We included 349 cases of pelvic tumors treated with internal hemipelvectomy and reconstruction in our center from January 2009 to May 2015. None of these cases had major lumbosacral nerves invaded by the tumors. Demographic and medical data were reviewed and documented for statistical analyses. The locations of lateral lumbar vertebral body screws (LLVBSs) were evaluated in 26 cases. RESULTS: The overall incidence of post-operative neuralgia was 8.3 %. Pre-admission requirement of analgesics (OR 4.089; 95 % CI 1.711 9.774) and application of LLVBS (OR 11.848; 95 % CI 4.369-32.129) were independent risk factors of neuralgia. The horizontal location of LLVBS did not affect the incidence of neuralgia when it was placed near the midline of the vertebra. CONCLUSIONS: The incidence of post-operative neuralgia was 8.3 % in this study cohort. The LLVBS technique could increase the risk of post-operative neuralgia. PMID- 27384779 TI - Organ donation opt-out law is saving lives in Wales. AB - More lives are being saved through organ donations thanks to groundbreaking legislation, says the Welsh Government. PMID- 27384778 TI - Enjoy exploring our redesigned magazine and website. AB - Welcome to your new-look Emergency Nurse - we hope you like what you see. The publication has been redesigned to create a fresher, more modern and reader friendly feel, based on what our reader research told us you wanted. PMID- 27384777 TI - Anterior release for Scheuermann's disease: a systematic literature review and meta-analysis. AB - PURPOSE: Anterior release for Scheuermann's disease was considered an important technique for decades. However, posterior-only surgery for Scheuermann's disease has shown a promising potential to manage this deformity, as well. Correction loss could happen post-operatively, especially when posterior-only surgery is performed in the early days. Therefore, a dispute regarding anterior release for Scheuermann's disease exists. METHODS: We performed a systematic review of studies, reporting the outcomes of anterior release and posterior fusion surgery (AP group) or posterior-only surgery (PO group) for Scheuermann's disease. Data pooling and a meta-analysis with a random-effects model were performed to evaluate the results. RESULTS: Twenty-three studies met the inclusion criteria. The pooled correction loss of Cobb angle for the AP group was 4.1(3.4, 4.8), and for the PO group, it was 3.8(3.3, 4.4). The overall effects of blood loss, surgery time, proximal junctional kyphosis (PJK), distal junctional kyphosis (DJK), self-image improvement, pain relief, and return-to-surgery were compared between the two groups. CONCLUSIONS: A systematic review of the outcomes of Scheuermann's disease demonstrated a very similar correction loss for the AP group and the PO group. A meta-regression supported that correction loss did decrease as time moved on for the PO procedure, which could be explained by the improvements to instrumentation and techniques. For other outcomes, the PO group showed advantages in blood loss, surgery time, and junctional kyphosis. Similar outcomes were observed in relation to aspects of cosmetic improvement and pain relief for the AP and PO groups. The revision rate was mildly lower in the PO group than in the AP group. PMID- 27384780 TI - All-week GPs reduce ED attendances. AB - The number of visits to emergency departments (EDs) has dropped since the launch of a government pilot to open GP surgeries 7 days a week. PMID- 27384781 TI - Warning boosts nurse numbers. AB - Managers at a north London emergency department (ED) are boosting nurse numbers on each shift to avoid action being taken by the Care Quality Commission (CQC) over failure to improve care. PMID- 27384782 TI - RCN calls for children to receive CPR training. AB - Children across the UK should learn cardiopulmonary resuscitation (CPR) to equip them to save lives, politicians have been told. PMID- 27384785 TI - New career pathways developed for emergency nurses in Northern Ireland. AB - A career framework for nurses in emergency care settings in Northern Ireland is due to be launched by the autumn. PMID- 27384783 TI - Infirmary appeals for Twiddlemuff knitters. AB - An appeal for knitters has been launched by Leicester Royal Infirmary's emergency department (ED) to help dementia patients. PMID- 27384786 TI - Story in numbers. AB - Attendances and emergency admissions in England. PMID- 27384787 TI - College backs domestic abuse awareness training. AB - All nurses should be trained to recognise signs of domestic abuse and provide support to victims, according to a resolution overwhelmingly backed by RCN members at congress in Glasgow last month. PMID- 27384788 TI - Leading Change, Adding Value. AB - Essential facts Leading Change, Adding Value is NHS England's new nursing and midwifery framework. It builds on Compassion in Practice (CiP), which set out the 6Cs. While CiP established the values of nursing and midwifery, the new framework explains how staff can help transform the health and care sectors to meet the aims of the NHS England's Five Year Forward View. PMID- 27384789 TI - Emergency care staff need new tools to improve vital signs tests. AB - Worrying gaps in how children are assessed in emergency departments (EDs) have been identified in an audit of emergency services. PMID- 27384793 TI - Patients need to be better informed about emergency trials. AB - This article explores public opinion on clinical trials in emergency departments (EDs). PMID- 27384792 TI - Profiling frequent ED attendees. AB - A small number of patients who were frequent and inappropriate users of emergency departments in Canada were studied to see what they had in common. PMID- 27384794 TI - Other scans. PMID- 27384795 TI - 'Surviving the knocks in ED made me a better nurse'. AB - Do you remember your first day in the emergency department? I do. For me, it was the fulfilment of a dream I had long before nursing school. PMID- 27384796 TI - Nursing values stand against those of Brexit. AB - It is a strange feeling to be working on this article in the middle of June. For as I sit and write there is still uncertainty about the nature of the UK's relationship with the European Union. PMID- 27384797 TI - From twitter. AB - Nurses on Twitter. PMID- 27384800 TI - Understanding Nursing and Healthcare Research Cronin Patricia , Coughlan Michael and Smith Valerie Understanding Nursing and Healthcare Research 224pp L20.99 Sage 9781446241011 1446241017 [Formula: see text]. AB - The 12 chapters cover key topics in the nursing and healthcare research process, including data collection, data analysis, and quantitative and qualitative approaches. PMID- 27384799 TI - Think before you bounce. AB - In recent years, trampolining has become a common recreational activity for children and young people. Its popularity in the UK has been on the increase since 2005, reflected in the sale of almost 250,000 trampolines in 2014 ( RoSPA 2015 ) and the emergence of indoor trampoline parks and trampolining as a competitive sport ( Council on Sports Medicine and Fitness 2012 ). PMID- 27384801 TI - E-rostering can boost staff contentment and bring in real flexibility. AB - I had the opportunity of working with an American e-rostering system that offered real advantages. The system proved a time-saver for senior staff, providing accurate and timely access to staffing at local and senior level, as well as fairness, equity of shift patterns and easy management of leave. PMID- 27384803 TI - Zika virus: emergency and aftercare of patients. AB - Zika virus, a mosquito-borne vector, is an emerging population health threat, and is linked to fetal microcephaly, pregnancy loss and neurologic symptoms like Guillain-Barre syndrome. Global travel and migration increase the risk of transmission significantly, and growing numbers of cases are expected internationally. This article describes transmission of the virus, early and late clinical manifestations, and emergency and supportive care. It also recommends interventions for prevention. PMID- 27384804 TI - Medication errors in intensive care units: nurses' training needs. AB - AIM: To describe which elements of nurses' knowledge, training, behaviour and attitude can prevent errors in intensive care units during all steps of the administration of intravenous medication. METHOD: An anonymous questionnaire made up of 43 items was drafted and delivered to a sample of 123 nurses at 2 university hospitals in Rome. RESULTS: The majority of the sample (96.7%) stated that topics related to the preparation and administration of intravenous medications were covered during the basic nursing course. Just over 95% of the sample considered it important to improve their knowledge about preparation and administration of intravenous medications; 94.3% said that teaching about the use of intravenous medications should be enhanced during the degree course they attended and 91.1% agreed that specific postgraduate courses should be set up on the use of intravenous drugs. CONCLUSION: Pharmacological knowledge is a prerequisite for the proper administration of drugs and for the clinical evaluation of the effects on the patient. This knowledge implies the understanding of the theoretical and clinical principles of pharmacology, the ability to contextualise medication management according to the complex and changing needs of patients, and it also includes the appropriate skills of drug administration. PMID- 27384805 TI - Management of head injuries in children. AB - Head injury is the most common cause of injury-related death and permanent disability in children. Minor head trauma is common in childhood and does not require any medical treatment. Although deficits can occur even after mild to moderate head injury, they are markedly greater and become clinically evident following severe head injury. It is important that emergency department clinicians are aware of the signs and symptoms that indicate severe traumatic brain injury and triage for urgent intervention in those children who present with these signs and symptoms. Clinicians also need to know when children can be sent home with reassurance and information, and when they require admission or transfer to a neurosurgical unit. This article examines the literature on head injuries in children, describes assessment, management and treatment, and provides a simple management algorithm. PMID- 27384807 TI - Online. AB - There is evidence for collaboration between police officers and mental health teams when responding to people in mental health crises. PMID- 27384806 TI - 'It is important to value people's contributions'. AB - What is your job? I lead a programme supporting trusts to improve unscheduled care for patients in Northern Ireland. I support implementation of best practice across the health system. PMID- 27384808 TI - In other RCNi journals. AB - 'A technique that encourages people to take notice of their thoughts and reactions, internally and externally, by being non-judgemental. It is worth exploring the potential benefits for people with learning disabilities, and those who care for or work alongside them'. PMID- 27384809 TI - Attitudes towards patients with cancer who smoke. AB - This article describes the findings of a mixed-methods study exploring healthcare professionals' attitudes towards patients with cancer who smoke, and how this impacts on the health promotion advice that they provide. Findings revealed that staff are aware of the effects of smoking on a patient's cancer treatments, however the number of staff that address smoking cessation with patients is variable. Staff also reported particular concerns about addressing smoking cessation with palliative patients. PMID- 27384810 TI - Violence against older women. AB - Domestic abuse is widespread and indiscriminate. Older women living with domestic abuse experience a number of health-related concerns and significant mental health issues. Research suggests that the needs of older women experiencing domestic abuse are not being met by existing services. This article examines the issues that older women face as a result of abusive relationships and the barriers to seeking help. Research suggests that a stepped approach, tailored to suit older women's needs, could be beneficial. PMID- 27384811 TI - Leading on waste reduction. AB - Waste in the NHS is estimated to account for 20% of health expenditure. This article examines the literature on reducing waste, analyses some approaches to waste reduction, and identifies the role that nurses and other health professionals can play in developing a sustainable NHS. To inform nursing practice, the definition of, and discussion about, waste includes clinical waste, waste arising out of clinical practice, service delivery and care, infrastructure, and carbon emissions. PMID- 27384812 TI - Chemical composition and antioxidant capacity of acai (Euterpe oleracea) genotypes and commercial pulps. AB - BACKGROUND: Acai has been reported to contain many bioactive compounds, including phenolic compounds such as anthocyanins. This study aimed to determine the chemical composition and antioxidant potential of pulps of three different acai genotypes from the Active Germplasm Bank of Embrapa Eastern Amazon and three commercial acai pulps from Belem, state of Para, Brazil. RESULTS: Anthocyanin 3 rutinoside was the major anthocyanin present in freeze-dried acai pulp samples. The commercial sample C showed the greatest amounts of cyanidin 3-glucoside and cyanidin 3-rutinoside (18 942 and 34 397 ug g-1 respectively). The content of phenolic compounds varied significantly among the commercial and genotype samples, and vanillic acid was found in the highest concentration in the samples studied. All acai samples showed high DPPH, ORAC and TEAC values, confirming the exceptionally high radical-scavenging capacity of acai pulp previously reported by other researchers. CONCLUSION: The commercial samples showed higher antioxidant capacity and higher levels of anthocyanins and non-anthocyanic compounds than those of the genotype samples. Among the genotypes studied, L4P16 stood out for its higher contents of fibre and bioactive compounds and higher antioxidant capacity, indicating that this genotype has great potential for use in plant breeding programs that should be further explored. (c) 2016 Society of Chemical Industry. PMID- 27384813 TI - Increased frequency of self-fertile isolates in Phytophthora infestans may attribute to their higher fitness relative to the A1 isolates. AB - Knowledge of population dynamics of mating types is important for better understanding pathogen's evolutionary potential and sustainable management of natural and chemical resources such as host resistances and fungicides. In this study, 2250 Phytophthora infestans isolates sampled from 61 fields across China were assayed for spatiotemporal dynamics of mating type frequency. Self-fertile isolates dominated in ~50% of populations and all but one cropping region with an average frequency of 0.64 while no A2 isolates were detected. Analyses of 140 genotypes consisting of 82 self-fertile and 58 A1 isolates indicated that on average self-fertile isolates grew faster, demonstrated higher aggressiveness and were more tolerant to fungicides than A1 isolates; Furthermore, pattern of association between virulence complexity (defined as the number of differential cultivars on which an isolate can induce disease) and frequency was different in the two mating types. In A1 isolates, virulence complexity was negatively correlated (r = -0.515, p = 0.043) with frequency but this correlation was positive (r = 0.532, p = 0.037) in self-fertile isolates. Our results indicate a quick increase of self-fertile isolates possibly attributable to their higher fitness relative to A1 mating type counterpart in the field populations of P. infestans in China. PMID- 27384814 TI - Longitudinal Antibiotic Susceptibility Profiles of Staphylococcus aureus Cutaneous Infections in a Pediatric Outpatient Population. AB - This longitudinal update on Staphylococcus aureus prevalence and antibiotic resistance patterns surveyd 291 cultures from 188 patients in a pediatric outpatient dermatology clinic with suspected skin and soft tissue infections. The prevalence of methicillin-resistant Staphylococcus aureus remained stable at 24%. Staphylococcus aureus resistance to tetracyclines modestly but demonstrably increased in the interval since 2009. PMID- 27384815 TI - Tetranitro-oxacalix[4]crown-Based Host-Guest Recognition Motif and a Related [2]Rotaxane-Based Molecular Switch. AB - Different from so far reported oxacalix[4]crown-based host-guest motifs in which oxacalix[4]crowns act only as hydrogen bond acceptors, a [2]pseudorotaxane-type tetranitro-oxacalix[4]crown/urea host-guest recognition motif was developed in which tetranitro-oxacalix[4]crown played a role as both a hydrogen bond donor and an acceptor to stabilize the resulting supramolecular complex. Furthermore, on the basis of a [2]pseudorotaxane complex formed from a tetranitro oxacalix[4]crown and an axle containing a secondary ammonium ion and a urea group, a [2]rotaxane-based molecular switch was created, in which the oxacalix[4]crown wheel was able to reversibly translocate between the secondary ammonium binding site and the urea binding site of the axle under acid-base stimulation. PMID- 27384817 TI - Probing the energy levels of perovskite solar cells via Kelvin probe and UV ambient pressure photoemission spectroscopy. AB - The field of organo-lead halide perovskite solar cells has been rapidly growing since their discovery in 2009. State of the art devices are now achieving efficiencies comparable to much older technologies like silicon, while utilising simple manufacturing processes and starting materials. A key parameter to consider when optimising solar cell devices or when designing new materials is the position and effects of the energy levels in the materials. We present here a comprehensive study of the energy levels present in a common structure of perovskite solar cell using an advanced macroscopic Kelvin probe and UV air photoemission setup. By constructing a detailed map of the energy levels in the system we are able to predict the importance of each layer to the open circuit voltage of the solar cell, which we then back up through measurements of the surface photovoltage of the cell under white illumination. Our results demonstrate the effectiveness of air photoemission and Kelvin probe contact potential difference measurements as a method of identifying the factors contributing to the open circuit voltage in a solar cell, as well as being an excellent way of probing the physics of new materials. PMID- 27384816 TI - The effect of cataract surgery on salivary melatonin and sleep quality in aging people. AB - Blue light plays an important role in circadian photoentrainment by stimulating the melanopsin-expressing photosensitive retinal ganglion cells. Age-related cataract causes progressive loss of blue light transmission, which may lead to changes in circadian rhythm and sleep quality. In theory, increased light transmission by cataract surgery may improve circadian misalignment and sleep quality, while the effect of cataract surgery on circadian rhythm is not well understood. In this study, we assessed 30 binocular age-related nuclear cataract patients (aged 72.5 +/- 7.2, 16 female) who were eligible for cataract surgery. All the patients underwent phacoemulsification cataract extraction and neutral ultraviolet-only blocking intraocular lens (IOLs) implantation. Visual functions including best-corrected visual acuity (BCVA), color perception and dark adaptation were assessed. Salivary samples were collected at 1-hour interval from 19:00 to 23:00 48 hours before and after surgery. Salivary melatonin concentration was measured and dim light melatonin onset (DLMO) was calculated subsequently. Sleep quality and daytime alertness were assessed before and a month after surgery using Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). All the operated eyes demonstrated significant improvements in BCVA, color perception and dark adaptation after cataract surgery. Salivary melatonin concentration at 23:00 was significantly increased after surgery (P < 0.001). However, the average DLMO did not change significantly after surgery. In addition, PSQI and ESS scores were significantly decreased a month after surgery (P = 0.027, P < 0.001, respectively). In conclusion, cataract surgery promotes blue-light transmission; consequently, it may lead to the increase in nighttime melatonin concentration and improvement in sleep quality as well as daytime alertness. PMID- 27384819 TI - Keratin Durability Has Implications for the Fossil Record: Results from a 10 Year Feather Degradation Experiment. AB - Keratinous 'soft tissue' structures (i.e. epidermally derived and originally non biomineralized), include feathers, skin, claws, beaks, and hair. Despite their relatively common occurrence in the fossil record (second only to bone and teeth), few studies have addressed natural degradation processes that must occur in all organic material, including those keratinous structures that are incorporated into the rock record as fossils. Because feathers have high preservation potential and strong phylogenetic signal, in the current study we examine feathers subjected to different burial environments for a duration of ~10 years, using transmission electron microscopy (TEM) and in situ immunofluorescence (IF). We use morphology and persistence of specific immunoreactivity as indicators of preservation at the molecular and microstructural levels. We show that feather keratin is durable, demonstrates structural and microstructural integrity, and retains epitopes suitable for specific antibody recognition in even the harshest conditions. These data support the hypothesis that keratin antibody reactivity can be used to identify the nature and composition of epidermal structures in the rock record, and to address evolutionary questions by distinguishing between alpha- (widely distributed) and beta- (limited to sauropsids) keratin. PMID- 27384820 TI - Serious disease outbreaks caused by viruses transmitted by Aedes aegypti in Brazil. PMID- 27384818 TI - Occupational Exposure to Pesticides and the Incidence of Lung Cancer in the Agricultural Health Study. AB - BACKGROUND: Occupational pesticide use is associated with lung cancer in some, but not all, epidemiologic studies. In the Agricultural Health Study (AHS), we previously reported positive associations between several pesticides and lung cancer incidence. OBJECTIVE: We evaluated use of 43 pesticides and 654 lung cancer cases after 10 years of additional follow-up in the AHS, a prospective cohort study comprising 57,310 pesticide applicators from Iowa and North Carolina. METHODS: Information about lifetime pesticide use and other factors was ascertained at enrollment (1993-1997) and updated with a follow-up questionnaire (1999-2005). Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for smoking (smoking status and pack-years), sex, and lifetime days of use of any pesticides. RESULTS: Hazard ratios were elevated in the highest exposure category of lifetime days of use for pendimethalin (1.50; 95% CI: 0.98, 2.31), dieldrin (1.93; 95% CI: 0.70, 5.30), and chlorimuron ethyl (1.74; 95% CI: 1.02, 2.96), although monotonic exposure response gradients were not evident. The HRs for intensity-weighted lifetime days of use of these pesticides were similar. For parathion, the trend was statistically significant for intensity-weighted lifetime days (p = 0.049) and borderline for lifetime days (p = 0.073). None of the remaining pesticides evaluated was associated with lung cancer incidence. CONCLUSIONS: These analyses provide additional evidence for an association between pendimethalin, dieldrin, and parathion use and lung cancer risk. We found an association between chlorimuron ethyl, a herbicide introduced in 1986, and lung cancer that has not been previously reported. Continued follow-up is warranted. PMID- 27384821 TI - Zika virus: what do we know about the viral structure, mechanisms of transmission, and neurological outcomes? AB - The Zika virus epidemic that started in Brazil in 2014 has spread to >30 countries and territories in Latin America, leading to a rapid rise in the incidence of microcephalic newborns and adults with neurological complications. At the beginning of the outbreak, little was known about Zika virus morphology, genome structure, modes of transmission, and its potential to cause neurological malformations and disorders. With the advancement of basic science, discoveries of the mechanisms of strain variability, viral transfer to the fetus, and neurovirulence were published. These will certainly lead to the development of strategies to block vertical viral transmission, neuronal invasion, and pathogenesis in the near future. This paper reviews the current literature on Zika virus infections, with the aim of gaining a holistic insight into their etiology and pathogenesis. We discuss Zika virus history and epidemiology in Brazil, viral structure and taxonomy, old and newly identified transmission modes, and neurological consequences of infection. PMID- 27384822 TI - Could Plasmodium vivax malaria trigger malnutrition? Revisiting the Bradford Hill criteria to assess a causal relationship between two neglected problems. AB - The benign characteristics formerly attributed to Plasmodium vivax infections have recently changed owing to the increasing number of reports of severe vivax malaria resulting in a broad spectrum of clinical complications, probably including undernutrition. Causal inference is a complex process, and arriving at a tentative inference of the causal or non-causal nature of an association is a subjective process limited by the existing evidence. Applying classical epidemiology principles, such as the Bradford Hill criteria, may help foster an understanding of causality and lead to appropriate interventions being proposed that may improve quality of life and decrease morbidity in neglected populations. Here, we examined these criteria in the context of the available data suggesting that vivax malaria may substantially contribute to childhood malnutrition. We found the data supported a role for P. vivax in the etiology of undernutrition in endemic areas. Thus, the application of modern causal inference tools, in future studies, may be useful in determining causation. PMID- 27384823 TI - Evaluation and optimization of SYBR Green real-time reverse transcription polymerase chain reaction as a tool for diagnosis of the Flavivirus genus in Brazil. AB - INTRODUCTION: The genus Flavivirus includes several pathogenic species that cause severe illness in humans. Therefore, a rapid and accurate molecular method for diagnosis and surveillance of these viruses would be of great importance. Here, we evaluate and optimize a quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) method for the diagnosis of the Flavivirus genus. METHODS: We evaluated different commercial kits that use the SYBR Green system for real-time RT-PCR with a primer set that amplifies a fragment of the NS5 flavivirus gene. The specificity and sensitivity of the assay were tested using twelve flaviviruses and ribonucleic acid (RNA) transcribed from the yellow fever virus. Additionally, this assay was evaluated using the sera of 410 patients from different regions of Brazil with acute febrile illness and a negative diagnosis for the dengue virus. RESULTS: The real-time RT-PCR amplified all flaviviruses tested at a melting temperature of 79.92 to 83.49 degrees C. A detection limit of 100 copies per ml was determined for this assay. Surprisingly, we detected dengue virus in 4.1% (17/410) of samples from patients with febrile illness and a supposedly negative dengue infection diagnosis. The viral load in patients ranged from 2.1*107to 3.4*103copies per ml. CONCLUSIONS: The real-time RT-PCR method may be very useful for preliminary diagnoses in screenings, outbreaks, and other surveillance studies. Moreover, this assay can be easily applied to monitor viral activity and to measure viral load in pathogenesis studies. PMID- 27384824 TI - High prevalence of plasmid-mediated quinolone resistance determinants in Enterobacter cloacae isolated from hospitals of the Qazvin, Alborz, and Tehran provinces, Iran. AB - INTRODUCTION: Plasmid-mediated quinolone resistance (PMQR) is a growing clinical concern worldwide. The main aims of this study were to detect qnr-encoding genes and to evaluate the clonal relatedness of qnr-positive Enterobacter cloacae isolates. METHODS: A total of 116 E. cloacae isolates that were not susceptible to quinolone were obtained from seven hospitals in Tehran, five hospitals in Qazvin, and two hospitals in Karaj (Iran). Bacterial identification was performed using standard laboratory methods and API 20E strips. Quinolone resistance was determined using the Kirby-Bauer disk diffusion method according to the Clinical Laboratory Standards Institute (CLSI) guidelines. PCR and sequencing were employed to detect qnrA, qnrB, and qnrS genes, and clonal relatedness was assessed using the enterobacterial repetitive intergenic consensus (ERIC)-PCR method. RESULTS: In total, 45 (38.8%) and 71 (61.2%) of isolates showed high- and low-level quinolone resistance, respectively, and qnr-encoding genes were detected in 70 (60.3%) of them. qnrB1 [45 (38.8%) isolates] was the most commonly detected gene, followed by qnrS1 [28 (24.1%) isolates] and qnrB4 [18 (15.5%) isolates] either alone or in combination with other genes. The results of the ERIC-PCR revealed that 53 (75.7%) qnr-positive isolates were genetically unrelated. CONCLUSIONS: This study describes, for the first time, the high prevalence of the qnrB1, qnrS1, and qnrB4 genes among E. cloacae isolates in Iran. The detection of qnr genes emphasizes the need for establishing tactful policies associated with infection control measures in hospital settings in Iran. PMID- 27384825 TI - Coagulase-negative staphylococci in Southern Brazil: looking toward its high diversity. AB - INTRODUCTION: Coagulase-negative staphylococci (CoNS) are the most prevalent pathogens in nosocomial infections and may serve as a reservoir of mobile genetic elements such as the staphylococcal cassette chromosome mec (SCCmec) encoding methicillin resistance. Molecular characterization of SCCmec types combined with advanced molecular typing techniques may provide essential information for understanding the evolution and epidemiology of CoNS infections. We therefore aimed to investigate the SCCmec distribution, multidrug-resistance (MDR), and biofilm formation in CoNS blood culture isolates from a hospital in Southern Brazil. METHODS: We analyzed 136 CoNS blood culture isolates obtained during 2002 2004 from patients admitted to a tertiary care hospital in Brazil. SCCmec types I to V were determined using multiplex PCR. The clonal relationship of Staphylococcus epidermidis was determined using pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Molecular epidemiological data were interpreted along with data on biofilm formation, presence of the icaD gene, and MDR. RESULTS: The most prevalent species were S. epidermidis, Staphylococcus haemolyticus, and Staphylococcus hominis harboring mainly SCCmec types II, III, and V. Overall, the presence of multiple SCCmec was associated with non-MDR, except for S. epidermidis. S. epidermidis isolates showed a high prevalence of icaD, but had low phenotypic biofilm formation. PFGE and MLST revealed high genetic diversity in the S. epidermidis population. CONCLUSIONS: Our results suggest a major shift in SCCmec types within a short period and reveal a different behavior of S. epidermidis with regard to the association between the presence of multiple SCCmec types and MDR profile. PMID- 27384826 TI - Antimicrobial susceptibility of Acinetobacter clinical isolates and emerging antibiogram trends for nosocomial infection management. AB - INTRODUCTION: The drug resistant Acinetobacter strains are important causes of nosocomial infections that are difficult to control and treat. This study aimed to determine the antimicrobial susceptibility patterns of Acinetobacter strains isolated from different clinical specimens obtained from patients belonging to different age groups. METHODS: In total, 716 non-duplicate Acinetobacter isolates were collected from the infected patients admitted to tertiary-care hospitals at Lahore, Pakistan, over a period of 28 months. The Acinetobacter isolates were identified using API 20E, and antimicrobial susceptibility testing was performed and interpreted according to Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: The isolation rate of Acinetobacter was high from the respiratory specimens, followed by wound samples. Antibiotic susceptibility analyses of the isolates revealed that the resistance to cefotaxime and ceftazidime was the most common, in 710 (99.2%) specimens each, followed by the resistance to gentamicin in 670 (93.6%) isolates, and to imipenem in 651 (90.9%) isolates. However, almost all isolates were susceptible to tigecycline, colistin, and polymyxin B. CONCLUSIONS: The present study showed the alarming trends of resistance of Acinetobacter strains isolated from clinical specimens to the various classes of antimicrobials. The improvement of microbiological techniques for earlier and more accurate identification of bacteria is necessary for the selection of appropriate treatments. PMID- 27384827 TI - Clinical and microbiological features of infections caused by Pseudomonas aeruginosa in patients hospitalized in intensive care units. AB - INTRODUCTION: The spread of multidrug-resistant Pseudomonas aeruginosa in Brazilian hospitals has greatly impacted upon the morbidity and mortality of individuals in intensive care units. Given the lack of information regarding the dynamics of multidrug resistance in northern Brazil, we analyzed the clinical and microbiological features of nosocomial infections caused by P. aeruginosa. METHODS: Between January 2010 and March 2012, we conducted a retrospective cohort study of P. aeruginosa isolates from 54 patients who were hospitalized in intensive care units. The clinical and epidemiologic variables were analyzed, including the patients' demographic data and comorbidities, and the lengths of the intensive care unit stays, the classification of the infections as nosocomial, the use of invasive procedures, antimicrobial therapy, and the patients' outcomes. We undertook susceptibility tests, molecular detection of the metallo-beta-lactamase genes, and genotypic analyses of the isolates using the repetitive element-polymerase chain reaction. RESULTS: Multidrug resistance occurred most frequently among isolates from adults who had been hospitalized for an average of 87.1 days. The use of mechanical ventilation and urinary catheters were risk factors for infection. The four isolates that harbored the blaSPM-1 like gene showed >95% genetic similarity. CONCLUSIONS: This study's findings show that P. aeruginosa has a high death rate, and that inadequate treatment and invasive procedures are risk factors for infection. This is the first report describing the detection of the blaSPM-1-like gene in northern Brazil. These results highlight the need for better monitoring and a greater understanding of nosocomial infections and their public health impacts. PMID- 27384828 TI - Prevalence and factors associated with Chlamydia trachomatis infection among women with HIV in Sao Paulo. AB - INTRODUCTION: This study aimed to estimate the prevalence and risk factors associated with Chlamydia trachomatis (CT) infection among women with HIV in Sao Paulo. METHODS: This cross-sectional study included women with HIV who were receiving care from sixteen public health services in Sao Paulo (October 2013 to March 2014). All participants answered a questionnaire regarding their sociodemographic, behavioral, and clinical characteristics. A urine sample was tested for CT and Neisseria gonorrhoeae (NG) using the polymerase chain reaction. The chi-square test and a logistic regression model were used to test the associations with CT or NG infections. RESULTS: We evaluated 853 women and ultimately included 836 (98%) women. The mean age was 40.5 +/- 0.34 years, and the prevalences of CT and NG infections were 1.8% and 0.5%, respectively. CT infection was associated with CD4+ T-cell counts of <350 cells/mm3 [adjusted odds ratio (ORadj): 24.5], age of 18-25 years (ORadj: 23.2), the non-use of condoms during the last 6 months (ORadj: 10.2), a self-reported history of a sexually transmitted infection (ORadj: 9.4), and having two or more sexual partners during the last year (ORadj: 6.1). CONCLUSIONS: Although we observed a low prevalence of CT infection among women with HIV, younger age was associated with a high risk of infection. Therefore, it may be appropriate to include screening for CT as part of the routine care for this population. PMID- 27384829 TI - Cardiac rehabilitation program in patients with Chagas heart failure: a single arm pilot study. AB - INTRODUCTION: The benefit of a cardiac rehabilitation (CR) program for patients with Chagas heart failure (CHF) remains unclear. Therefore, we aimed to investigate the effects of CR for CHF patients. METHODS: A single-arm pilot study, including 12 patients with CHF, was performed. Patients participated in an 8-month physical exercise intervention, comprising aerobic, strength, and stretching exercises (3 times per week, 60 minutes per session). Nutritional and pharmaceutical counseling were also performed. Functional capacity (cardiopulmonary exercise test), muscle respiratory strength (manovacuometry), and body composition (anthropometry and skinfolds) were evaluated at baseline, and after 4 and 8 months of intervention. Cardiac function (echocardiography), biomarkers (lipid profile, glucose, and glycated hemoglobin) and quality of life (Minnesota Living with Heart Failure Questionnaire) were assessed at baseline and at the end of the intervention. RESULTS: Seven of 12 patients included in the study completed the 8-month follow-up period. Only 2 moderate adverse events occurred during the exercise training. Functional capacity improved after 4 months of CR, while left ventricular ejection fraction (LVEF) and respiratory strength improved after 8 months. Patients with right ventricular (RV) dysfunction at baseline exhibited an improvement in functional capacity after 4 months, and improvements in left ventricular (LV) diastolic pressure, respiratory strength, and quality of life at the end of follow-up. Conversely, those with normal baseline RV function demonstrated LVEF increases that were not observed in patients with RV dysfunction. CONCLUSIONS: CR was feasible, safe, and has important clinical benefits for patients with CHF, specifically for cardiac function and muscle respiratory strength. PMID- 27384830 TI - Does my patient have chronic Chagas disease? Development and temporal validation of a diagnostic risk score. AB - INTRODUCTION: With the globalization of Chagas disease, unexperienced health care providers may have difficulties in identifying which patients should be examined for this condition. This study aimed to develop and validate a diagnostic clinical prediction model for chronic Chagas disease. METHODS: This diagnostic cohort study included consecutive volunteers suspected to have chronic Chagas disease. The clinical information was blindly compared to serological tests results, and a logistic regression model was fit and validated. RESULTS: The development cohort included 602 patients, and the validation cohort included 138 patients. The Chagas disease prevalence was 19.9%. Sex, age, referral from blood bank, history of living in a rural area, recognizing the kissing bug, systemic hypertension, number of siblings with Chagas disease, number of relatives with a history of stroke, ECG with low voltage, anterosuperior divisional block, pathologic Q wave, right bundle branch block, and any kind of extrasystole were included in the final model. Calibration and discrimination in the development and validation cohorts (ROC AUC 0.904 and 0.912, respectively) were good. Sensitivity and specificity analyses showed that specificity reaches at least 95% above the predicted 43% risk, while sensitivity is at least 95% below the predicted 7% risk. Net benefit decision curves favor the model across all thresholds. CONCLUSIONS: A nomogram and an online calculator (available at http://shiny.ipec.fiocruz.br:3838/pedrobrasil/chronic_chagas_disease_prediction/) were developed to aid in individual risk estimation. PMID- 27384831 TI - Performance of POC-CCA(r) in diagnosis of schistosomiasis mansoni in individuals with low parasite burden. AB - INTRODUCTION: Schistosomiasis, caused by Schistosoma mansoni, is a public health concern in Brazil. However, the most popular diagnostic method, the Kato-Katz technique, exhibits low sensitivity in low-endemicity areas. We aimed to compare the performance of an immunological assay, the point-of-care circulating cathodic antigen (POC-CCA(r)) test, with that of two parasitological techniques in a low endemicity population. METHODS: Our study included 141 individuals living in Estreito de Miralta, Minas Gerais, Brazil. Fecal samples were obtained from all participants and analyzed for schistosomiasis using two parasitological techniques: the Kato-Katz technique and the saline gradient technique. Additionally, POC-CCA(r) strips were utilized for testing urine samples. The results obtained by the different techniques were compared. RESULTS: Analysis of two or 24 slides using the Kato-Katz technique resulted in a positivity rate of 10.6% (15/141) or 19.1% (27/141), respectively. The saline gradient technique yielded a positivity rate of 17.0% (24/141). The prevalence according to both parasitological techniques was 24.1% (34/141). The POC-CCA(r) test yielded a positivity rate of 22.7% (32/141); however, the positivity rate was merely 2.1% if trace results were considered negative. The agreements observed between POC CCA(r) and the parasitological techniques were good (Kappa indexes > 0.64). The POC-CCA(r) test was more sensitive than the two-slide Kato-Katz technique (p < 0.05) in detecting cases of S. mansoni infection when trace results were considered positive. CONCLUSIONS: These findings reinforce the importance of using multiple diagnostic techniques in low-endemicity areas for effective control of disease. PMID- 27384832 TI - Serological evidence of hantavirus infection in an urban area in Mato Grosso State, Brazil. AB - INTRODUCTION: In Brazil, Mato Grosso (MT) has the highest number of hantavirus cardiopulmonary syndrome cases. Our study aimed to identify anti-hantavirus antibodies in the sera of patients from Sinop, MT, presenting with acute febrile illness. METHODS: A retrospective analysis of data for 198 sera samples assessed using enzyme-linked immunosorbent assay (ELISA) was conducted. RESULTS: Immunoglobulins G (IgGs) against the hantavirus nucleoprotein were found in 13.6% of the tested sera. No sample had immunoglobulin M (IgM) antibodies to hantavirus. Seropositivity occurred mainly in female residents in urban areas who worked around the household. CONCLUSIONS: Our findings suggest circulation of hantavirus in Sinop. PMID- 27384833 TI - Diversity of yellow fever mosquito vectors in the Atlantic Forest of Rio de Janeiro, Brazil. AB - INTRODUCTION: Environmental modifications caused by human activities have led to changes in mosquito vector populations, and sylvatic species have adapted to breeding in urban areas. METHODS: Mosquitoes were collected using ovitraps in three sampling sites in the Atlantic Forest in the State of Rio de Janeiro, Brazil. RESULTS: We collected 2,162 Culicidae specimens. Haemagogus janthinomys and Haemagogus leucocelaenus, both sylvatic yellow fever virus vectors, were the most common species found. CONCLUSION: There is a potential for the transmission of arboviruses in and around these natural reserves. Therefore, it is necessary to maintain entomological surveillance programs in the region. PMID- 27384834 TI - Detection of antibodies to Oropouche virus in non-human primates in Goiania City, Goias. AB - INTRODUCTION: Arboviruses are associated with human disease, and non-human primates (NHPs) are important primary hosts. This study shows the detection of antibodies to Oropouche virus (OROV) in NHPs either living in urban parks or acclimatized at the Wild Animal Screening Center, Goiania city. METHODS: Fifty blood samples were analyzed by hemagglutination-inhibition and neutralization assays. RESULTS: Two monkeys (Alouatta caraya) had antibodies to OROV by both techniques. CONCLUSIONS: This is the first report demonstrating the detection of OROV antibodies in Goias State and may represent the introduction/circulation of OROV in the region and a potential risk to the human population. PMID- 27384835 TI - Canine antibody response to Lutzomyia longipalpis saliva in endemic area of visceral leishmaniasis. AB - INTRODUCTION: Canine exposure to Lutzomyia longipalpis bites and the potential of Leishmania infantum transmissibility for the vector were evaluated. METHODS: Immunoglobulin G (IgG) anti-Lu longipalpis saliva and -L. infantum, and blood parasite load were determined in dogs from endemic areas of visceral leishmaniasis. RESULTS: Blood parasitism was similar between symptomatic and asymptomatic dogs. IgG anti-L. infantum was higher in symptomatic dogs, but IgG anti-Lu. longipalpis saliva was mostly observed in higher titers in asymptomatic dogs, indicating vector preference for feeding on asymptomatic dogs. CONCLUSIONS: Our data suggest a pivotal role of asymptomatic dogs in L. infantum transmission in endemic areas. PMID- 27384836 TI - First report of Rhodnius stali (Hemiptera, Reduviidae, Triatominae) in the State of Acre and in the Brazilian Amazon. AB - INTRODUCTION: This paper reports, for the first time, the presence of Rhodnius stali in the state of Acre and in the Brazilian Amazon. METHODS: Specimens of R. stali were collected by the Federal University of Acre in Rio Branco. RESULTS: The number of Triatominae species in the State of Acre increased from five to six. This was also the first report of R. stali in the Brazilian Amazon. CONCLUSIONS: The occurrence of R. stali is worrisome, since this species has been found naturally infected by Trypanosoma cruzi and there has been evidence of its domiciliation capabilities. PMID- 27384837 TI - Semisolid liver infusion tryptose supplemented with human urine allows growth and isolation of Trypanosoma cruzi and Trypanosoma rangeli clonal lineages. AB - INTRODUCTION: This work shows that 3% (v/v) human urine (HU) in semisolid Liver Infusion Tryptose (SSL) medium favors the growth of Trypanosoma cruzi and T. rangeli. METHODS: Parasites were plated as individual or mixed strains on SSL medium and on SSL medium with 3% human urine (SSL-HU). Isolate DNA was analyzed using polymerase chain reaction (PCR) and pulsed-field gel electrophoresis (PFGE). RESULTS: SSL-HU medium improved clone isolation. PCR revealed that T. cruzi strains predominate on mixed-strain plates. PFGE confirmed that isolated parasites share the same molecular karyotype as parental cell lines. CONCLUSIONS: SSL-HU medium constitutes a novel tool for obtaining T. cruzi and T. rangeli clonal lineages. PMID- 27384838 TI - Analysis of cutaneous tuberculosis cases reported from 2000 to 2013 at a university hospital in Rio de Janeiro. AB - INTRODUCTION: Tuberculosis (TB) is a serious public health problem; however, the cutaneous form remains rare. METHODS: A retrospective analysis examined notified cutaneous tuberculosis (CTB) cases from 2000 to 2013 at the University Hospital Clementino Fraga Filho. RESULTS: Twenty-six CTB cases were documented during this period. Erythema induratum of Bazin was the most common form, and 86.7% of such cases occurred in women (p=0.068). Only one patient was HIV positive. CONCLUSIONS: This study confirms the rarity of CTB and highlights the need for multicenter studies in order to obtain an adequate number of cases for analysis. PMID- 27384839 TI - A profile of scorpionism, including the species of scorpions involved, in the State of Amazonas, Brazil. AB - INTRODUCTION: This study investigated scorpionism profile in the State of Amazonas, Brazil. METHODS: Data referring to stinging incidents were obtained from the National Databank of Major Causes of Morbidity. Information on the scorpion species involved was obtained from the Amazonas State health units. RESULTS: Amazonas has a scorpionism rate of 8.14 cases/100,000 inhabitants. Some municipalities (e.g., Apui) presented higher rates (273 cases/100,000 inhabitants). Most species involved in envenomation belonged to the genus Tityus. CONCLUSIONS: Our results reaffirm the notion of scorpionism being a public health hazard and provide data that can guide public policy aimed at scorpionism prevention and treatment. PMID- 27384840 TI - Dengue as a cause of fever during pregnancy: a report of two cases. AB - Dengue infection has not been routinely investigated among pregnant women and parturients with acute febrile syndrome in endemic settings. Here, we report two cases of dengue fever detected at the time of delivery in parturients enrolled in a cohort prospective study conducted in a hospital in Recife, Brazil. The parturients reported fever onset within seven days prior to delivery, and dengue infection was confirmed upon detection of viral ribonucleic acid (RNA) by using the reverse transcriptase-polymerase chain reaction. Dengue infection should be considered as a diagnostic possibility in cases of fever during pregnancy and labor, especially in endemic areas. PMID- 27384841 TI - Neurobrucellosis and venous sinus thrombosis: an uncommon association. AB - Brucellosis is a commonly diagnosed zoonosis and neurological involvement is rare. A 30-year-old woman presented with a pulsatile headache that was exacerbated by the Valsalva maneuver and refractory to analgesic therapy. The patient also had nausea, cough, and coryza that evolved over 7 days. The neurological examination was unremarkable. Thrombosis of the lateral and sigmoid sinus and ipsilateral internal jugular vein were diagnosed and anticoagulation therapy was started. Brucella spp was identified in a sample of cerebrospinal fluid (CSF); five months after treatment with rifampicin and doxycycline, CSF was sterile. Cerebral venous thrombosis is a very uncommon sign of brucellosis. PMID- 27384842 TI - Chronic kidney disease related to renal tuberculosis: a case report. AB - Genitourinary tuberculosis (TB) is the third most common form of extrapulmonary TB. A 34-year-old man with severe kidney function loss secondary to renal TB initially presented with urinary symptoms, including dysuria and polacyuria. The diagnosis was based on clinical history and laboratory tests; the urinalysis revealed acid-fast bacilli. The patient's condition stabilized after beginning TB specific treatment, but the right kidney function loss persisted. Renal TB can lead to irreversible loss of renal function. As such, renal function should be considered in all patients from TB-endemic areas who present with urinary symptoms and whose urine cultures are negative for common pathogens. PMID- 27384843 TI - Hallux amputation after a freshwater stingray injury in the Brazilian Amazon. AB - Freshwater stingray injuries are a common problem in the Brazilian Amazon, affecting mostly riverine and indigenous populations. These injuries cause severe local and regional pain, swelling and erythema, as well as complications, such as local necrosis and bacterial infection. Herein, we report a case of bacterial infection and hallux necrosis, after a freshwater stingray injury in the Brazilian Amazon, which eventually required amputation. Different antimicrobial regimens were administered at different stages of the disease; however, avoiding amputation through effective treatment was not achieved. PMID- 27384844 TI - Two cases of lepidopterism caused by indoor exposure to moths. PMID- 27384846 TI - [Not Available]. PMID- 27384845 TI - Aedes aegypti (Diptera: Culicidae) in a tree hole in Brazil. PMID- 27384847 TI - Current issues concerning drug development for pediatric hematologic malignancies. AB - Cure rates for pediatric hematologic malignancies (HM) have improved dramatically due to the intensive use of conventional chemotherapy and hematopoietic stem cell transplantation. However, many children still die of their disease or treatment related toxicities. Even in patients experiencing an apparent cure, there can be significant acute and late complications of treatment. Further improvements of therapy will likely depend on the development of new therapeutic strategies. Immune-based therapy, for example monoclonal antibody-based and adoptive T-cell therapies, offers an attractive alternative that has emerged as a potent treatment strategy. Drug repositioning of molecular target drugs is now receiving remarkable attention, especially that based on recent genome wide studies. However, there are many obstacles to overcome in developing these novel drugs for pediatric patients. Pediatric drug development is difficult in itself because many of these agents are not profitable, largely due to their being too few patients, preclinical models are limited, there are too few formulations for children, special ethical considerations must be addressed when treating children and so on. Obstacles to the development of new drugs are a characteristic feature of pediatric HM. Furthermore, the approach to developing drugs for pharmaceutical approval is quite different from that to developing new therapies using approved drugs and is not well-known among investigators. Although many challenges remain in pediatric hematologic anticancer drug development, none are insurmountable. PMID- 27384848 TI - Gene-modified T-cell therapy using chimeric antigen receptors for pediatric hematologic malignancies. AB - Chimeric antigen receptor (CAR) is the generic name for synthetic T cell receptors redirected to tumor-associated antigens. Most CARs consist of an ectodomain (scFv or ligand), a hinge region, a transmembrane domain, and signaling endodomains derived from one or two co-stimulatory molecules (CD28, 4 1BB, etc) and from a CD3-zeta chain. CD19-targeted CAR T cell therapy has achieved major success in the treatment of B cell malignancies. CD19 CAR-T cells elicited complete remission in 70-90% of adult and pediatric patients with relapsed/refractory acute lymphoblastic leukemia (ALL). CD19 CAR T cell therapy from allogeneic donors including third party donors is a potential option for B cell malignancies. CAR T cell therapies for myeloma, acute myeloid leukemia, and T-cell leukemia are still under development. Our group is currently preparing a phase I study of CD19 CAR T cell therapy in pediatric and young adult patients with ALL using a non-viral gene transfer method, the piggyBac-transposon system. PMID- 27384849 TI - A bispecific antibody mimicking factor VIII in hemophilia A therapy. AB - Serious issues in current hemostatic treatment of hemophilia A are the requirement for frequent intravenous administrations of factor (F) VIII, FVIII inhibitor development, and hemostatic treatment for patients with this inhibitor. For the purpose of overcoming these challenges, the FVIIIa-substituting bispecific antibody against FIXa/FX (ACE910, INN emicizumab) was produced. Emicizumab demonstrated marked hemostatic effects on both ongoing and spontaneous joint bleeding in the acquired hemophilia A primate model. The clinical phase 1 study designed to assess the pharmacokinetics, pharmacodynamics and safety of emicizumab has been initiated. Severe emicizumab-related adverse events were minimal. The t1/2 was approximately 30 days, and bleeding events were significantly decreased by weekly subcutaneous administration in severe hemophilia A patients, independently of the presence of the inhibitor. Currently, the phase 1/2 extension study is ongoing. We anticipate that emicizumab will show the benefits of prophylactic efficacy with subcutaneous administration at a much lower frequency. PMID- 27384850 TI - Significance of TET2 mutations in myeloid and lymphoid neoplasms. AB - The TET2 gene is an epigenetic regulator. Loss-of-function mutations of TET2 are found in a variety of blood cancers in both myeloid and lymphoid lineages. Meanwhile, clonal blood cells carrying leukemia-driver mutations have been detected in significant proportions of different cohorts without blood cancers. Amongst these driver mutations, those in the TET2 gene are second/third most frequent. The presence of such clonal blood cells predicts elevated risk for developing various blood cancers. These results indicate that acquisition of TET2 mutations in blood cells does not per se cause cancers; however, TET2 mutations are likely to be acquired at the common myeloid/lymphoid progenitor levels. Such hematopoietic stem/progenitor cells may wait for second hit mutations for the development of multiple blood cancers, and play a role as pre-leukemia/pre lymphoma cells. Combinations of TET2 and disease-specific gene mutations have been demonstrated in individual blood cancers. Correspondingly, mice into which such combinatorial gene abnormalities have been introduced will recapitulate the respective blood cancers. PMID- 27384851 TI - Clonal evolution in myelodysplastic syndromes. AB - During the past ten years, genome-wide analysis of genetic alterations in myelodysplastic syndromes (MDS) has improved our understanding of their pathogenesis. Especially, single nucleotide polymorphism array karyotyping and next-generation sequencing technologies (NGS) have unveiled frequent genetic changes in novel functional pathways, including DNA methylation, RNA splicing and cohesin complex formation, in MDS. Moreover, NGS shed light on the clonal evolution which occurs during the development and progression of MDS, pre cancerous lesions of MDS, and the effects of germline mutations in MDS. PMID- 27384852 TI - Genetic predisposition to pediatric myeloid malignancies. AB - Various genetic disorders are known to be associated with cancer predisposition. For example, children with Down syndrome are predisposed to developing acute myeloid leukemia, and those with RASopathies, such as Noonan syndrome, are predisposed to juvenile myelomonocytic leukemia. To date, more than 250 diseases or syndromes have been reported to be associated with the development of pediatric cancers. Recently, the advent of the massive parallel sequencing technique revealed several germline mutations, including RUNX1, CEBPA, GATA2, SRP72, ETV6, and DDX41, which are associated with familial myeloid malignancies. A significant number of children with myeloid malignancies may harbor pathognomonic germline variants. It is strongly recommended that precise diagnosis, genetic counseling, familial screening, and follow-up programs be provided for patients with such a predisposition to cancer. To identify genetic disorders associated with predispositions to pediatric myeloid malignancies, the development of an efficient screening system with the massive parallel sequencer for germline and somatic mutations, which would also be useful for familial genetic studies and prediction of tumor progression, is needed. PMID- 27384853 TI - Early diagnosis and successful treatment of disseminated toxoplasmosis after cord blood transplantation. AB - A 66-year-old woman with refractory angioimmunoblastic T-cell lymphoma underwent cord blood transplantation. Prior to transplantation, a serological test for Toxoplasma gondii-specific IgG antibodies was positive. On day 96, she exhibited fever and dry cough. Chest CT showed diffuse centrilobular ground glass opacities in both lungs. The reactivation of T. gondii was identified by the presence of parasite DNA in peripheral blood and bronchoalveolar lavage fluid. Moreover, brain MRI revealed a space occupying lesion in the right occipital lobe. Therefore, disseminated toxoplasmosis was diagnosed. She received pyrimethamine and sulfadiazine from day 99. The lung and brain lesions both showed improvement but the PCR assay for T. gondii DNA in peripheral blood was positive on day 133. On day 146, she developed blurred vision and reduced visual acuity, and a tentative diagnosis of toxoplasmic retinochoroiditis was made based on ophthalmic examination results. As agranulocytosis developed on day 158, we decided to discontinue pyrimethamine and sulfadiazine and the treatment was thus switched to atovaquone. Moreover, we added spiramycin to atovaquone therapy from day 174, and her ocular condition gradually improved. In general, the prognosis of disseminated toxoplasmosis after hematopoietic stem cell transplantation (HSCT) is extremely poor. However, early diagnosis and treatment may contribute to improvement of the fundamentally dismal prognosis of disseminated toxoplasmosis after HSCT. PMID- 27384854 TI - Successful non-myeloablative allogenic bone marrow transplantation in a child with severe congenital neutropenia complicated by chronic pulmonary infection. AB - We herein describe a 2-year-old boy with severe congenital neutropenia (SCN) who was successfully treated with reduced-intensity bone marrow transplantation (HSCT). He had suffered recurrent episodes of bacterial pneumonia from 12 months of age, and was found to have severe neutropenia with white blood cell counts below 100/MUl. The patient harbored a heterozygous missense mutation in ELANE exon 4 (p.Gln134Pro, NM_001972.2: c.401A>C). This was a novel mutation. Due to intractable pneumonia and severe persistent neutropenia, reduced-intensity HSCT was performed from an HLA-matched sibling donor. The preparative regimen consisted of melphalan, fludarabine, and 4 Gy of total body irradiation. Hematopoietic engraftment was rapidly obtained, i.e., by day +14, and complete donor chimerism was subsequently achieved. The lung complications observed pre transplantation markedly improved after neutrophil recovery, i.e., by day +60. We concluded that HSCT is a useful treatment for SCN patients, especially for those at high risk of leukemic transformation. Fludarabine-based reduced-intensity HSCT may represent a safe and effective therapeutic option for patients with SCN who need HSCT even if they have intractable infectious complications. PMID- 27384855 TI - Severe 6-mercaptopurine-induced hematotoxicity in childhood an ALL patient with homozygous NUDT15 missence variants. AB - Thiopurine S-methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X type motif 15 (NUDT15) variants are considered to be genes responsible for severe myelotoxicity induced by 6-mercaptopurine (6MP). We report a 4-year-old girl with acute lymphoblastic leukemia, who developed the complication of severe 6MP induced myelotoxicity due to homozygous NUDT15 variant alleles. In early consolidation therapy containing 6MP, her course was complicated by severe neutropenia (Grade 4) and chemotherapy had to be discontinued for 33 days. The 6MP dose was subsequently adjusted based on the white blood cell count. The ratios of the prescribed 6MP dose over the protocol dose in early consolidation, central nervous system (CNS) prophylaxis, re-induction, interim maintenance and maintenance therapy were 63%, 27%, 4%, 26% and 7%, respectively. Suspension of therapy was required during early consolidation, CNS prophylaxis and interim maintenance therapy. We investigated candidate genes for 6MP-associated myelotoxicity and found homozygous NUDT15 variant alleles and a heterozygous inosine triphosphate pyrophosphatase (ITPA) variant allele. In patients with homozygous NUDT15 variants, drastic reduction (less than 10%) of the 6MP dose from the protocol dose might be required not only during maintenance therapy, but also during other treatment courses containing 6MP. Screening of candidate genes at diagnosis is recommended in order to avoid serious adverse events. PMID- 27384856 TI - Spontaneous splenic rupture in a patient with light-chain deposition disease undergoing autologous peripheral blood stem cell transplantation. AB - Light-chain deposition disease (LCDD) is a rare plasma cell neoplasm that secretes an abnormal immunoglobulin light chain, which is deposited in tissues, leading to organ dysfunction. Spontaneous splenic rupture is a rare and life threatening complication of treatment with granulocyte colony-stimulating factor (G-CSF). Herein, we describe spontaneous splenic rupture after the administration of lenograstim to a patient with LCDD undergoing autologous stem cell transplantation (ASCT). The patient was successfully treated by transcatheter embolization of the splenic artery, and long-term stringent complete remission was attained. Plasma cell neoplasms, including multiple myeloma with amyloidosis, are among the most commonly reported conditions associated with spontaneous splenic rupture in patients undergoing ASCT. This finding suggests that, in addition to the effect of G-CSF on the spleen, a combination of factors, including tissue vulnerability induced by the infiltration of abnormal immunoglobulins, may be involved in the pathogenesis of spontaneous splenic rupture. Notably, splenomegaly is not always evident in these patients. Surgical treatment may not be an option, because of severe myelosuppression, and thus less invasive treatment using transcatheter embolization may be feasible. PMID- 27384857 TI - Successful high-dose dexamethasone treatment of acquired pure red cell aplasia following ABO major mismatched allogeneic hematopoietic stem cell transplantation. AB - A 46-year-old man was diagnosed with acute myelomonocytic leukemia involving inv(16)(p13.1q22) in August 2007. He received a human leukocyte antigen identical, ABO major-mismatched (donor: A, recipient: O) bone marrow transplantation from an unrelated donor in June 2009. Cyclosporin A (CsA) and short-course methotrexate were used for graft versus host disease prophylaxis. Although granulocyte and platelet engraftment were achieved, the patient exhibited persistent anemia and was dependent on red blood cell (RBC) transfusions. Bone marrow aspiration on day 63 revealed the near absence of erythroid precursors, a finding consistent with pure red cell aplasia. No CBFbeta MYH11 transcripts were detected. The recipient's anti-A IgM antibody titer was 1:64, and his anti-A IgG antibody titer was 1:1024. The discontinuation of CsA, and the initiation of rituximab and donor lymphocyte infusions were all ineffective against his anemia. He was treated with high-dose dexamethasone (DEXA) (40 mg/day DEXA, days 657-660, days 757-760; 20 mg/day DEXA, days 764-767, days 772-775) in April 2010. A follow-up examination performed at 7 months after the high-dose DEXA treatment showed the patient's anti-A antibody titer to have dropped to an undetectable level. His hemoglobin levels also returned to normal (Hb: 13.4 g/dl), and he no longer required RBC transfusions. PMID- 27384858 TI - Severe stomatitis and ileocecal perforation developed after all-trans retinoic acid monotherapy in an HLA-B51-positive patient with acute promyelocytic leukemia. AB - A 34-year-old man who had been referred to our hospital was diagnosed with acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA), oral administration, was initiated. On day 25, he developed fever and respiratory distress with bilateral pulmonary infiltrates, suggesting differentiation syndrome (DS) caused by ATRA. These symptoms showed amelioration after discontinuing ATRA and initiating methylprednisolone. ATRA was re-started on day 29 at half the original dose because of residual APL blasts. The patient subsequently developed fever, severe stomatitis, and oropharyngeal ulcers, which persisted even after discontinuing ATRA. On day 48, he suddenly developed severe abdominal pain with free air, observable on an abdominal X-ray, and underwent emergency ileocecal resection. Pathological examination of the resected ileocecal intestines revealed multiple ulcers and perforations. No leukemic cell infiltration was observed. In this case, only ATRA was administered for APL treatment. These findings suggest that ileocecal ulcerations and perforations, as well as oropharyngeal ulcers, might have been caused by DS or ATRA. Furthermore, DNA typing of the HLA-B locus revealed that the patient had HLA-B51 associated with Behcet's disease. Therefore, hypercytokinemia with DS might have induced Behcet's disease-like symptoms, including stomatitis and ileocecal perforation, complications that are particularly observed in patients with HLA-B51. PMID- 27384859 TI - Repeated rituximab-induced serum sickness with anaphylaxis. AB - We describe a patient who developed repeated rituximab-induced serum sickness (RISS) followed by anaphylaxis soon after the third administration of rituximab at relapse. A 65-year-old woman with Sjogren's syndrome and relapsed mucosal associated lymphoma tissue (MALT) lymphoma of the lung underwent rituximab monotherapy (375 mg/m(2)/week). Several days after the second exposure to rituximab, she developed a rash, fever, and arthralgia. These symptoms showed relief, but a severe anaphylactic reaction occurred when she was treated with rituximab for the third time. Although a rare complication in patients with lymphoma, clinicians should be aware of RISS symptoms and avoid repeatedly administering rituximab to such patients. PMID- 27384861 TI - [Not Available]. PMID- 27384860 TI - [Not Available]. PMID- 27384862 TI - [Not Available]. PMID- 27384863 TI - [Not Available]. PMID- 27384864 TI - Testing the Effectiveness of Cognitive Analytic Therapy for Hypersexuality Disorder: An Intensive Time-Series Evaluation. AB - The evidence base for treatment of hypersexuality disorder (HD) has few studies with appropriate methodological rigor. This study therefore conducted a single case experiment of cognitive analytic therapy (CAT) for HD using an A/B design with extended follow-up. Cruising, pornography usage, masturbation frequency and associated cognitions and emotions were measured daily in a 231-day time series. Following a three-week assessment baseline (A: 21 days), treatment was delivered via outpatient sessions (B: 147 days), with the follow-up period lasting 63 days. Results show that cruising and pornography usage extinguished. The total sexual outlet score no longer met caseness, and the primary nomothetic hypersexuality outcome measure met recovery criteria. Reduced pornography consumption was mediated by reduced obsessionality and greater interpersonal connectivity. The utility of the CAT model for intimacy problems shows promise. Directions for future HD outcome research are also provided. PMID- 27384865 TI - Sonar beam dynamics in leaf-nosed bats. AB - Ultrasonic emissions of bats are directional and delimit the echo-acoustic space. Directionality is quantified by the aperture of the sonar beam. Recent work has shown that bats often widen their sonar beam when approaching movable prey or sharpen their sonar beam when navigating through cluttered habitats. Here we report how nose-emitting bats, Phyllostomus discolor, adjust their sonar beam to object distance. First, we show that the height and width of the bats sonar beam, as imprinted on a parabolic 45 channel microphone array, varies even within each animal and this variation is unrelated to changes in call level or spectral content. Second, we show that these animals are able to systematically decrease height and width of their sonar beam while focusing on the approaching object. Thus it appears that sonar beam sharpening is a further, facultative means of reducing search volume, likely to be employed by stationary animals when the object position is close and unambiguous. As only half of our individuals sharpened their beam onto the approaching object we suggest that this strategy is facultative, under voluntary control, and that beam formation is likely mediated by muscular control of the acoustic aperture of the bats' nose leaf. PMID- 27384867 TI - Successful orthotopic heart transplantation using a donor heart with ALCAPA. AB - With the imbalance between donation rates and potential recipients growing, transplant programs are increasingly using non-ideal organs from so-called marginal donors. This is the first reported case of the intentional use of a donor heart with ALCAPA. The recipient was aged one yr with restrictive cardiomyopathy who had been supported with BiVAD for over six months. Function of the donor left ventricle was shown to be well preserved, with no obvious signs of ischemia, except for a fibrotic layer on the anterolateral papillary muscle of the mitral valve. To prevent coronary steal, the anomalous left coronary artery ostium from the MPA was oversewn prior to implantation. The transplanted heart spontaneously regained sinus rhythm immediately following cross-clamp release and showed good contractility from the first postoperative echocardiogram. The patient continues to do well 18 months post-transplant, with excellent function on echocardiography, and good flow on coronary angiography. PMID- 27384866 TI - Jun N-terminal kinase signaling makes a face. AB - decapentaplegic (dpp), the Drosophila ortholog of BMP 2/4, directs ventral adult head morphogenesis through expression in the peripodial epithelium of the eye antennal disc. This dpp expressing domain exerts effects both on the peripodial epithelium, and the underlying disc proper epithelium. We have uncovered a role for the Jun N-terminal kinase (JNK) pathway in dpp-mediated ventral head development. JNK activity is required for dpp's action on the disc proper, but in the absence of dpp expression, excessive JNK activity is produced, leading to specific loss of maxillary palps. In this review we outline our hypotheses on how dpp acts by both short range and longer range mechanisms to direct head morphogenesis and speculate on the dual role of JNK signaling in this process. Finally, we describe the regulatory control of dpp expression in the eye-antennal disc, and pose the problem of how the various expression domains of a secreted protein can be targeted to their specific functions. PMID- 27384868 TI - Serum IL-4 and IL-10 Levels Correlate with the Symptoms of the Drug-Naive Adolescents with First Episode, Early Onset Schizophrenia. AB - OBJECTIVE: In this study, it was aimed to understand the underlying possible immunopathogenesis of first episode, early onset schizophrenia (EOS) through profiling the T helper 1 (Th1) cell cytokines TNF-alpha, IFN-gamma, and IL-2, Th2 cell cytokines IL-4 and IL-10, Th17 cell cytokine IL-17A, and inflammatory cytokine IL-6. METHODS: The study included a total of 30 children, admitted to child psychiatry outpatient clinic aged between 10 and 17 years of age, who had not received prior therapy and were diagnosed with psychosis according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) as the patient group, and 26 age- and gender-matched children as the control group. Structured psychiatric interviews (K-SADS-PL and PANSS) were conducted with all participants. The BD Cytokine Bead Array Human Th1/Th2/Th17 Cytokine Kit is used for the measurement of serum cytokines, for example, IL-2, IL-4, IL-6, IL-10, IL 17A, TNF-alpha, and IFN-gamma. RESULTS: There was no significant difference between groups in terms of IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-alpha, and IFN gamma levels (p > 0.05). However, there was a significant correlation between IL 10 and IL-4 with negative symptoms of EOS (r = -0.65, p = 0.02 and r = 0.67, p = 0.02, respectively). CONCLUSION: IL4 and IL-10 levels have a relationship with negative symptoms of disease. Therefore, this study might suggest that immunological processes might have a role in the disease pathophysiology. PMID- 27384870 TI - Single-dose Antibiotic Prophylaxis in Regional Anesthesia: A Retrospective Registry Analysis. AB - BACKGROUND: Catheter-related infection is a serious complication of continuous regional anesthesia. The authors tested the hypothesis that single-dose antibiotic prophylaxis is associated with a lower incidence of catheter-related infections. METHODS: Our analysis was based on cases in the 25-center German Network for Regional Anesthesia database recorded between 2007 and 2014. Forty thousand three hundred sixty-two surgical patients who had continuous regional anesthesia were grouped into no antibiotic prophylaxis (n = 15,965) and single dose antibiotic prophylaxis (n = 24,397). Catheter-related infections in each group were compared with chi-square test after 1:1 propensity-score matching. Odds ratios (ORs [95% CI]) were calculated with logistic regression and adjusted for imbalanced variables (standardized difference more than 0.1). RESULTS: Propensity matching successfully paired 11,307 patients with single-dose antibiotic prophylaxis (46% of 24,397 patients) and with 11,307 controls (71% of 15,965 patients). For peripheral catheters, the incidence without antibiotics (2.4%) was greater than with antibiotic prophylaxis (1.1%, P < 0.001; adjusted OR, 2.02; 95% CI, 1.49 to 2.75, P < 0.001). Infections of epidural catheters were also more common without antibiotics (5.2%) than with antibiotics (3.1%, P < 0.001; adjusted OR, 1.94; 95% CI, 1.55 to 2.43, P < 0.001). CONCLUSIONS: Single dose antibiotic prophylaxis was associated with fewer peripheral and epidural catheter infections. PMID- 27384871 TI - Complex metal borohydrides: multifunctional materials for energy storage and conversion. AB - With the limited supply of fossil fuels and their adverse effect on the climate and the environment, it has become a global priority to seek alternate sources of energy that are clean, abundant, and sustainable. While sources such as solar, wind, and hydrogen can meet the world's energy demand, considerable challenges remain to find materials that can store and/or convert energy efficiently. This topical review focuses on one such class of materials, namely, multi-functional complex metal borohydrides that not only have the ability to store sufficient amount of hydrogen to meet the needs of the transportation industry, but also can be used for a new generation of metal ion batteries and solar cells. We discuss the material challenges in all these areas and review the progress that has been made to address them, the issues that still need to be resolved and the outlook for the future. PMID- 27384869 TI - IL-17A-producing CD30(+) Vdelta1 T cells drive inflammation-induced cancer progression. AB - Although it has been suspected that inflammation is associated with increased tumor metastasis, the exact type of immune response required to initiate cancer progression and metastasis remains unknown. In this study, by using an in vivo tumor progression model in which low tumorigenic cancer cells acquire malignant metastatic phenotype after exposure to inflammation, we found that IL-17A is a critical cue for escalating cancer cell malignancy. We further demonstrated that the length of exposure to an inflammatory microenvironment could be associated with acquiring greater tumorigenicity and that IL-17A was critical for amplifying such local inflammation, as observed in the production of IL-1beta and neutrophil infiltration following the cross-talk between cancer and host stromal cells. We further determined that gammadeltaT cells expressing Vdelta1 semi-invariant TCR initiate cancer-promoting inflammation by producing IL-17A in an MyD88/IL-23 dependent manner. Finally, we identified CD30 as a key molecule in the inflammatory function of Vdelta1T cells and the blockade of this pathway targeted this cancer immune-escalation process. Collectively, these results reveal the importance of IL-17A-producing CD30(+) Vdelta1T cells in triggering inflammation and orchestrating a microenvironment leading to cancer progression. PMID- 27384872 TI - A systematic characterization of the low-energy photon response of plastic scintillation detectors. AB - To characterize the low energy behavior of scintillating materials used in plastic scintillation detectors (PSDs), 3 PSDs were developed using polystyrene based scintillating materials emitting in different wavelengths. These detectors were exposed to National Institute of Standards and Technology (NIST)-matched low energy beams ranging from 20 kVp to 250 kVp, and to (137)Cs and (60)Co beams. The dose in polystyrene was compared to the dose in air measured by NIST-calibrated ionization chambers at the same location. Analysis of every beam quality spectrum was used to extract the beam parameters and the effective mass energy-absorption coefficient. Monte Carlo simulations were also performed to calculate the energy absorbed in the scintillators' volume. The scintillators' expected response was then compared to the experimental measurements and an energy-dependent correction factor was identified to account for low-energy quenching in the scintillators. The empirical Birks model was then compared to these values to verify its validity for low-energy electrons. The clear optical fiber response was below 0.2% of the scintillator's light for x-ray beams, indicating that a negligible amount of fluorescence contamination was produced. However, for higher-energy beams ((137)Cs and (60)Co), the scintillators' response was corrected for the Cerenkov stem effect. The scintillators' response increased by a factor of approximately 4 from a 20 kVp to a (60)Co beam. The decrease in sensitivity from ionization quenching reached a local minimum of about [Formula: see text] between 40 keV and 60 keV x-ray beam mean energy, but dropped by 20% for very low-energy (13 keV) beams. The Birks model may be used to fit the experimental data, but it must take into account the energy dependence of the kB quenching parameter. A detailed comprehension of intrinsic scintillator response is essential for proper calibration of PSD dosimeters for radiology. PMID- 27384873 TI - Palladium-catalyzed dearomatizing 2,5-alkoxyarylation of furan rings: diastereospecific access to spirooxindoles. AB - A protocol for Pd-catalyzed intra- and intermolecular 2,5-alkoxyarylation reactions of furans to diastereospecifically synthesize two series of spirooxindoles is reported. This protocol likely involves an intramolecular dearomatizing Heck-type alpha-arylation of the furan ring to produce a cyclic allylic palladium and the subsequent intra- or intermolecular introduction of an alkyloxyl group at the other alpha-position of the ring, with different facial selectivities. PMID- 27384874 TI - Increased FGF19 copy number is frequently detected in hepatocellular carcinoma with a complete response after sorafenib treatment. AB - The multi-kinase inhibitor sorafenib is clinically approved for the treatment of patients with advanced hepatocellular carcinoma (HCC). We previously reported that fibroblast growth factor 3 and 4 (FGF3/FGF4) amplification is a predictor of a response to sorafenib. This study aims to analyze the relationship between FGF FGF receptor (FGFR) genetic alterations and the response to sorafenib. Formalin fixed, paraffin-embedded tissue specimens from HCC patients who had achieved a complete response (CR, N=6) or non-CR (N=39) to sorafenib were collected and were examined for FGF-FGFR gene alterations using next generation sequencing and copy number assay. FGFR mutations were detected in 5 of 45 (11.1%) cases. There was no significant association between FGFR mutation status and the response to sorafenib. We detected no increase in the FGF3/FGF4 copy number in CR cases. An FGF19 copy number gain was detected more frequently among CR cases (2/6, 33.3%) than among non-CR cases (2/39, 5.1%) (P = 0.024, Chi-squared test). In conclusion, a copy number gain for FGF19 may be a predictor of a response to sorafenib, in addition to FGF3/FGF4 amplification. PMID- 27384875 TI - YBX1 regulates tumor growth via CDC25a pathway in human lung adenocarcinoma. AB - Y-box binding protein 1 (YBX1) is involved in the multi-tumor occurrence and development. However, the regulation of YBX1 in lung tumorigenesis and the underlying mechanisms, especially its relationship with CDC25a, was remains unclear. In this study, we analyzed the expression and clinical significance of YBX1 and CDC25a in lung adenocarcinoma and identified their roles in the regulation of lung cancer growth. The retrospective analysis of 116 patients with lung adenocarcinoma indicated that YBX1 was positively correlated with CDC25a expression. The Cox-regression analysis showed only high-ranking TNM stage and low CDC25a expression were an independent risk factor of prognosis in enrolled patients. High expression of YBX1 or CDC25a protein was also observed in lung adenocarcinoma cells compared with HLF cells. ChIP assay demonstrated the binding of endogenous YBX1 to the CDC25a promoter region. Overexpression of exogenous YBX1 up-regulated the expression of the CDC25a promoter-driven luciferase. By contrast, inhibition of YBX1 by siRNA markedly decreased the capability of YBX1 binding to CDC25a promoter in A549 and H322 cells. Inhibition of YBX1 expression also blocked cell cycle progression, suppressed cell proliferation and induced apoptosis via the CDC25a pathway in vitro. Moreover, inhibition of YBX1 by siRNA suppressed tumorigenesis in a xenograft mouse model and down-regulated the expression of YBX1, CDC25a, Ki67 and cleaved caspase 3 in the tumor tissues of mice. Collectively, these results demonstrate inhibition of YBX1 suppressed lung cancer growth partly via the CDC25a pathway and high expression of YBX1/CDC25a predicts poor prognosis in human lung adenocarcinoma. PMID- 27384879 TI - Limits of the Classical Concept of Concentration. AB - Solutions of very low concentrations cannot be treated by the usual concept of concentration. Stochastic calculations are performed for the analysis of such solutions containing one or a few molecule(s). It is concluded that these systems escape the usual concentration parameters. Two "case histories" are also shown for demonstration of the practical consequences of the theoretical analysis. PMID- 27384878 TI - Quantitative proteomics reveals molecular mechanism of gamabufotalin and its potential inhibition on Hsp90 in lung cancer. AB - Gamabufotalin (CS-6) is a major bufadienolide of Chansu, which shows desirable metabolic stability and less adverse effect in cancer therapy. CS-6 treatment inhibited the proliferation of NSCLC in a nanomolar range. And CS-6 could induce G2/M cell cycle arrest and apoptosis in A549 cells. However, its molecular mechanism in antitumor activity remains poorly understood. We employed a quantitative proteomics approach to identify the potential cellular targets of CS 6, and found 38 possible target-related proteins. Among them, 31 proteins were closely related in the protein-protein interaction network. One of the regulatory nodes in key pathways was occupied by Hsp90. Molecular docking revealed that CS-6 interacted with the ATP-binding sites of Hsp90. In addition, CS-6 inhibited the chaperone function of Hsp90 and reduced expression of Hsp90-dependent client proteins. Moreover, CS-6 markedly down-regulated the protein level of Hsp90 in tumor tissues of the xenograft mice. Taken together, our results suggest that CS 6 might be a novel inhibitor of Hsp90, and the possible network associated with CS-6 target-related proteins was constructed, which provided experimental evidence for the preclinical value of using CS-6 as an effective antitumor agent in treatment of NSCLC. PMID- 27384876 TI - miR-29c contribute to glioma cells temozolomide sensitivity by targeting O6 methylguanine-DNA methyltransferases indirectely. AB - Temozolomide (TMZ) is the most commonly used alkylating agent in glioma chemotherapy. However growing resistance to TMZ remains a major challenge to clinicians. The DNA repair protein O6-methylguanine-DNA methytransferase (MGMT) plays critical roles in TMZ resistance. Promoter methylation can inhibit MGMT expression and increase chemosensitivity. Here, we described a novel mechanism regulating MGMT expression. We showed that miR-29c suppressed MGMT expression indirectly via targeting specificity protein 1 (Sp1). MiR-29c overexpression increased TMZ efficacy in cultured glioma cells and in mouse xenograft models. The miR-29c levels were positively correlated with patient outcomes. Our data suggest miR-29c may be potential therapeutic targets for glioma treatment. PMID- 27384880 TI - The Role of the Therapist in Therapeutic Change: How Knowledge From Mental Health Can Inform Pediatric Rehabilitation. AB - The therapist is a neglected and poorly understood variable in pediatric rehabilitation. Much more attention has been paid to the role of intervention on client change than the role of therapist-related variables. This article synthesizes what is known in the adult and child mental health literature about the role of the therapist, and integrates this with work in pediatric rehabilitation. The article reviews the mental health literature on the therapist as a random variable associated with client outcomes (role of the therapist alone) and the role of three other therapist-related constructs: the therapist client relationship (therapist and client), treatment implementation (therapist and intervention), and therapy process (therapist, client, and intervention considered holistically). Implications for clinical practice in pediatric rehabilitation include recognition of change as a multi-determined phenomenon involving common therapist-related factors, the therapist's role in creating facilitative conditions for change (through supportive relationships, positive expectancies, and mastery and learning experiences), and the importance of training in collaborative partnership skills. A contextual approach to therapeutic change is advocated, in which psychosocial factors and mechanisms are acknowledged, the therapist is seen as crucial, and the intervention process is seen as the context or vehicle through which changes occur. PMID- 27384882 TI - Exosomes: scytales in the damaged heart. PMID- 27384881 TI - Role of newer and re-emerging older agents in the treatment of infections caused by carbapenem-resistant Enterobacteriaceae. AB - Antimicrobial resistance has been identified by the World Health Organization as "one of the three greatest threats to human health." Gram negative bacteria in particular drive this alarming trend. Carbapenem-resistant Enterobacteriaceae (CRE) such as Escherichia coli, Klebsiella pneumoniae, and Enterobacter species are of particular importance as they are associated with poor clinical outcomes and are common causes for a variety of infections including bacteremia, urinary tract infection, intra-abdominal infections and pneumonia. CRE are difficult to treat as carbapenem resistance is often accompanied by resistance to additional drug classes. For example, CRE may be extensively drug resistant or even pandrug resistant. Unfortunately, CRE infections have increased over the past 15 y while new and effective antibiotics have not kept pace. Recently, however, new agents have become available to help treat CRE infection, and several more are under development. This article reviews the efficacy, safety, and pharmacokinetic issues around 4 emerging agents to treat CRE - ceftazidime-avibactam, fosfomycin, tigecycline, and minocycline. In addition, an overview of agents in the antibiotic pipeline - meropenem-vaborbactam, imipenem-relebactam, plazomicin, and eravacycline is provided. More established agents, such as those in the polymyxin class and aminoglycoside class (other than the pipeline agent plazomicin), are not addressed here. PMID- 27384884 TI - Climate-mediated adaptation after mainland colonization of an ancestrally subtropical island lizard, Anolis carolinensis. AB - Climate-mediated evolution plays an integral role in species migration and range expansion. Gaining a clearer understanding of how climate affects demographic history and adaptation provides fundamental insight into the generation of intra- and interspecific diversity. In this study, we used the natural colonization of the green anole (Anolis carolinensis) from the island of Cuba to mainland North America to investigate the role of evolution at the niche, phenotypic and genetic levels after long-term establishment in a novel environment. The North American green anole occupies a broader range of thermal habitats than its Cuban sister species. We documented niche expansion in the mainland green anole, mediated primarily through adaptation to winter temperatures. Common garden experiments strongly suggest a genetic component to differences in thermal performance found between populations in different temperature regimes. Analysis of geographic variation in population structure based on 53 486 single nucleotide variants from RAD loci revealed increased genetic isolation between populations in different vs. similar thermal environments. Selection scans for environment-allele correlations reveal 19 genomic loci of known function that may have played a role in the physiological adaptation of A. carolinensis to temperate environments on the mainland. PMID- 27384885 TI - Absorption and Oxidation of Nitrogen Oxide in Ionic Liquids. AB - A new strategy for capturing nitrogen oxide, NO, from the gas phase is presented. Dilute NO gas is removed from the gas phase by ionic liquids under ambient conditions. The nitrate anion of the ionic liquid catalyzes the oxidation of NO to nitric acid by atmospheric oxygen in the presence of water. The nitric acid is absorbed in the ionic liquid up to approximately one mole HNO3 per mole of the ionic liquid due to the formation of hydrogen bonds. The nitric acid can be desorbed by heating, thereby regenerating the ionic liquid with excellent reproducibility. Here, time-resolved in-situ spectroscopic investigations of the reaction and products are presented. The procedure reveals a new vision for removing the pollutant NO by absorption into a non-volatile liquid and converting it into a useful bulk chemical, that is, HNO3 . PMID- 27384883 TI - Functional characterization of the 12p12.1 renal cancer-susceptibility locus implicates BHLHE41. AB - Genome-wide association studies have identified multiple renal cell carcinoma (RCC) susceptibility loci. Here, we use regional imputation and bioinformatics analysis of the 12p12.1 locus to identify the single-nucleotide polymorphism (SNP) rs7132434 as a potential functional variant. Luciferase assays demonstrate allele-specific regulatory activity and, together with data from electromobility shift assays, suggest allele-specific differences at rs7132434 for AP-1 transcription factor binding. In an analysis of The Cancer Genome Atlas data, SNPs highly correlated with rs7132434 show allele-specific differences in BHLHE41 expression (trend P value=6.3 * 10(-7)). Cells overexpressing BHLHE41 produce larger mouse xenograft tumours, while RNA-seq analysis reveals that constitutively increased BHLHE41 induces expression of IL-11. We conclude that the RCC risk allele at 12p12.1 maps to rs7132434, a functional variant in an enhancer that upregulates BHLHE41 expression which, in turn, induces IL-11, a member of the IL-6 cytokine family. PMID- 27384886 TI - Transcranial direct-current stimulation as treatment in epilepsy. AB - INTRODUCTION: Neuromodulation (NM) is a complementary therapy for patients with drug-resistant epilepsy. Vagal nerve stimulation and deep brain stimulation of the anterior thalamus are established techniques and have shown their efficacy in lowering seizure frequency, but they are invasive and rarely render patients seizure-free. Non-invasive NM techniques are therefore increasingly investigated in a clinical context. Areas covered: Current knowledge about transcranial direct current stimulation (tDCS) and other non-invasive NM in patients with epilepsy, based on the available animal and clinical studies from PubMed search. Expert commentary: tDCS modulates neuronal membrane potentials, and consequently alters cortical excitability. Cathodal stimulation leads to cortical inhibition, which is of particular importance in epilepsy treatment. The antiepileptic efficacy is promising but still lacks systematic studies. The beneficial effect, seen in ~20%, outlasts the duration of stimulation, indicating neuronal plasticity and is therefore of great interest to obtain long-term effects. PMID- 27384887 TI - Viewpoint regarding the limited nutrition education opportunities for physicians worldwide. AB - Current trends in obesity and modifiable chronic disease are on the rise globally. Yet in primary care nutrition and lifestyle counseling, potentially the 'first line of defense' to address public health concerns, is limited. Unfortunately, nutrition and lifestyle education in the medical education curriculum is minimal and, in many countries, on the decline. Patients however expect their primary healthcare provider to assist them with diet and lifestyle modification to prevent and delay progression of chronic disease. This is indeed a paradox: the lack of nutrition focused education expertise in the face of the increased demand for nutrition counseling being placed on the physician. Across many countries, programmes of nutrition-centered continuing education, both online and face to face, are scarce. There is a pressing need for these educational opportunities to improve physician knowledge and self-efficacy in integrating nutrition counseling into routine practice, with the ultimate goal of improving overall patient health outcomes. PMID- 27384888 TI - Steps to Writing an Effective Introduction. PMID- 27384889 TI - Indocyanine Green Near-Infrared Fluorescence in Pure Laparoscopic Living Donor Hepatectomy: a Reliable Road Map for Intra-Hepatic Ducts ? AB - Indocyanine green (ICG) near-infrared (NIR) fluorescence cholangiography (FC) has shown its usefulness to visualize the biliary ducts in open living donor hepatectomy (LDH) to check the intraoperative biliary anatomy. The fully laparoscopic LDH approach has been recently described. However, this procedure is very demanding for a possible misperception of right parenchymal transection line and the cut point of the lobar biliary ducts (BD). To explore the potential of ICG-NIR-FC method we report our experience in 11 fully laparoscopic left LDH using 5 different protocols. Protocol-A, consisted on intravenous (i.v.) ICG injection of 2.5 mg with immediate cut of the BD; -B, same dose and late cut; -C, 1 mg i.v. and late cut; -D, intra-cystic duct injection of 2.5 mg and immediate cut; -E, intra-cystic injection of 5 mg and immediate cut. Protocol-A showed fast fluorescence in the lobar artery and portal vein followed by the BD sheet; -B showed intraductal excretion with a high parenchymal signal; -C showed a very week signal; -D failed to visualize the ducts; -E showed a good signal without parenchymal fluorescence. ICG-NIR-FC is an additional method to visualize the lobar ducts in fully laparoscopy LDH, but still insufficient for the segmental ducts. PMID- 27384890 TI - Effect of Neoadjuvant Radiation Dose on Surgical and Oncological Outcome in Locally Advanced Esophageal Cancer. AB - INTRODUCTION: Neoadjuvant chemoradiation (CRT) confers a survival benefit in locally advanced esophageal cancer. The optimal dose of radiotherapy remains undefined. METHODS: From a prospective database, we identified patients who received CRT followed by Ivor Lewis esophagectomy. Surgical complications, pathological response, and oncological outcome were compared between patients who received a radiotherapy (RT) dose of 36 Gy (group1) versus a dose of > 40 Gy (group 1). RESULTS: 147 patients were evaluated: 109 received 36 Gy, while 38 received 41-50Gy. Mean age was 61 +/- 9 years (84% male). Median hospital stay was 16 days. Anastomotic leakage occurred in 4.0%. Pulmonary complications occurred in 41.8%, neither being influenced by RT dose. Complete resection (R0) was achieved in 95% (group 1) and 100% (group 2), P = 0.3. Pathological complete response (pCR) was observed in 19% (group 1) and 37% (group 1), P = 0.04. Local recurrence developed in 9% in group 1, and 3% in group 2 (P = 0.3), but regional recurrence developed significantly higher in the low dose group (18% vs 3%, P < 0.001). Metastatic recurrence occurred in 48% in group 1 and 13% in group 1 (P < 0.001). CONCLUSIONS: In patients with locally advanced esophageal cancer a higher RT dose does not affect surgical outcome, enhances pCR rate, and reduces the locoregional and metastatic recurrence risk. PMID- 27384891 TI - Prevention of Parastomal Hernia Using Pre-peritoneal Mesh - Long Term Outcome of a Prospective Study. AB - BACKGROUND: Parastomal hernia is a frequent complication after stoma formation. The objective of this prospective study was to find long-term outcome of prophylactic mesh placement in the pre-peritoneal space in order to prevent parastomal hernia. METHODS: Patients undergoing elective formation of permanent stoma were included in the study. A polypropylene mesh was placed in the pre peritoneal space without any anchoring stitches and bowel was taken out through a central circular hole made in the mesh. These patients were followed up for 5 years-by clinical examination and CT scan when needed. RESULTS: A total of 42 patients were included in the study. These patients were followed up for a median period of 60 months (range 32-100 months). Twelve patients died before the 5-year follow up due to causes unrelated to stoma. As two patients were unable to be contacted, 28 patients remained in the long-term follow up. Three cases of parastomal hernia were detected after 5 years. None of these patients required repairing of the parastomal hernia. However, a previous study conducted 3 years ago found 4 cases of parastomal hernia that was treated by resiting the stomas. Therefore the total number of parastomal hernia detected in our series is 7 (incidence 25%). CONCLUSION: Putting a pre-peritoneal polypropylene mesh is an easy, quick and inexpensive method, and easy to learn. The outcome is better than creating stomas without mesh, but further studies are needed to explore potential benefits of different types of mesh and their methods of positioning and anchoring. PMID- 27384892 TI - The CR-POSSUM Risk Calculator Predicts Failure of Enhanced Recovery after Colorectal Surgery. AB - AIMS: To determine predictors of failed enhanced recovery after surgery (ERAS) in patients after elective colorectal surgery. METHODS: A cohort of 55 patients undergoing elective colorectal surgery was monitored prospectively. Perioperative care was based on a previously established protocol for ERAS. Pre-, intra-, and postoperative parameters were analyzed to elicit predictors of ERAS failure. ERAS failure was defined as prolonged hospital stay (> 7 days). The risk calculator CR POSSUM was evaluated for its clinical utility. RESULTS: Body mass index (BMI) or the American Society of Anesthesiologists score (ASA) was not associated with ERAS failure on univariate analysis, but patients that failed ERAS were significantly older (64 y vs 54 y; p = 0.023). Prolonged length of stay (>7 days) was also associated with an open approach (p = 0.009), intraoperative nasogastric tube placement (p = 0.005), blood loss > 500 ml (p = 0.008), stoma formation (p = 0.006) and insertion of more than one intraabdominal drain during surgery (p = 0.005). Postoperative continuation of intravenous fluids (p = 0.027), reinsertion of urinary catheter (p = 0.045) and postoperative ileus (p = 0.020) were also strongly associated with delayed discharge on univariate analysis. After multivariate analysis the preoperative parameters CR-POSSUM score (p = 0.022), increasing BMI (p = 0.014) and preoperative albumin level (p = 0.031) were all independently associated with failure of ERAS. CONCLUSIONS: A variety of perioperative factors contribute to failure of ERAS in routine practice. CR POSSUM can help to identify patients at risk for possible failure of ERAS. This may help to optimize avoidable factors, or accommodate those patients likely to require a longer post-operative stay. PMID- 27384893 TI - Comparison of Predictive Factors For the Diagnosis and Clinical Course of Phyllodes Tumours of the Breast. AB - BACKGROUND: To compare predicting factors for the diagnosis and clinical course of benign and malign/borderline phyllodes tumours (PT) of the breast, and to discuss treatment modalities. METHODS: Clinical and demographic characteristics of the patients with histopathological diagnosis of phyllodes tumour were examined. Patients were divided into group 1 (benign PT) and group 2 (borderline/malignant PT). Groups were compared in terms of demographic and clinical characteristics. RESULTS: Of the patients studied, 37 (68.5%) had benign, 7 (12.9%) had borderline and 10 (18.5) had malignant histopa-thology. A statistically significant relationship was detected between the incidence of malignancy and mass diameter (p = 0.001) and age (p = 0.030) when the two groups were compared. Wide surgical excision was performed on 46 (82.5%) patients, simple mastectomy on 7 (13%) patients and modified radical mastectomy on one (1.9%) patient. Ten (18.5%) patients were re-operated for surgical margin positivity. Local recurrence was determined only in one (1.9%) patient. Distant metastasis due to malignant PT developed in two (3.7%) patients. CONCLUSION: Among the patients who were considered to have PT, malignancy was likely to be present, especially if the patient's age was over 40 and the diameter of the mass was above 33.5 mm. Therefore, in patients with similar characteristics, surgical margins should be kept slightly wider or wider excisions should be preferred with or without simultaneous reconstructive surgery in appropriate cases. PMID- 27384894 TI - Oncological and Surgical Outcome after Oncoplastic Breast Surgery. AB - BACKGROUND: Oncoplastic surgery combines breast-conserving treatment and plastic surgery techniques. The aim of the study was to identify breast and tumor-related characteristics that contribute to the rate of complications and recurrence. MATERIAL & METHODS: This retrospective study included 72 patients with a median follow-up of 32 months. For each patient, a comprehensive set of data was collected, including epidemiology, tumor characteristics, preoperative information, detailed pathology reports, radiotherapy treatment and type of surgical technique. The rate of complications, recurrence and survival were studied. RESULTS: Complete tumor removal was performed with clear margins in all patients but in 25 of them margins were less than 2 mm. One patient had local recurrence and another developed distant metastases. The study showed that the size of the margin was not predictive of recurrence as long as not positive; the greater the resection volume, the larger the excision margin. The resection size was the only factor influencing complications and no specific tumor-related factor significantly increased the complication rate. Surgical complications did not delay the initiation of chemotherapy and radiotherapy. CONCLUSION: This is the first oncoplastic study where both tumor and breast characteristics were analyzed using the most recent criteria of the literature. Oncoplastic surgery can be considered as oncologically safe. The resection size was the sole significant risk factor for postoperative complications. Complications after oncoplastic breast surgery did not differ neoadjuvant therapy. Long-term event free survival was excellent (96% at 7 years). PMID- 27384895 TI - Impact of Anxiety in Ambulatory Superficial Venous Surgery: A Prospective Study Using the HADS-A Scale. AB - BACKGROUND: The aim of the present prospective clinical study is to evaluate the impact of the level of anxiety in patients undergoing ambulatory superficial venous surgery (SVS) and to select a specific group of patients who need more of our attention to reduce the postoperative adverse events. SUBJECTS AND METHODS: Preoperative anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS), especially the HADS-A (Anxiety subscale) in 340 consecutive patients undergoing elective SVS. Venous disease was assessed in all patients according to the established CEAP classification, the Venous Clinical Severity and the Venous Disability scores. RESULTS: According to the HADS-A scores, we could distinguish two groups of patients, with (group A with score > 8; 61 patients) and without potential anxious state (group B with score < 7; 279 patients). Demographic data, varicose veins risk factors and preoperative symptoms were comparable in both groups. The median HADS-A score was 9 (8-17; IQR: 2) in group A and 3 (0-7; IQR: 3) in group B. The rate of complications or adverse events in the recovery room, the mean postoperative pain scores, the apprehension before discharge hospital and the incidence of unexpected hospitalisation rate were significantly higher in group A when compared with group B. CONCLUSIONS: We observed that the presence of preoperative anxiety, even although infrequent, was associated with high incidence of complications or adverse events in the recovery room and a greater postoperative pain level. In this context, this group of patients needs more of our attention, particularly to limit potential anxiety and improve their satisfaction score. PMID- 27384896 TI - Small Bowel Intussusception Caused by Multiple Intestinal Metastases from a Giant Cell Carcinoma of the Lung: a Case Report. AB - Small bowel obstruction (SBO) due to intussusception in adults is a rare condition. Diagnosis at the time of admission is usually challenging. More often than not, a bowel intussusception in adults is secondary to an organic condition, frequently malignancies. Therefore, a surgical approach is indicated most of the times. We report the case of a forty-nine years old lady presenting with a SBO secondary to small bowel metastases with two ileo-ileal intussusceptions, one of which was missed at initial surgical exploration. A giant cell carcinoma of the lung (GCCL) with small bowel metastases was diagnosed subsequently. The case is presented as well as a brief review of literature. PMID- 27384897 TI - Single-Centre 20-Year Experience with Surgical Treatment of Thymic Tumours. AB - BACKGROUND: Large single-centre institutional series on thymic tumours are rare. Complete resection remains the mainstay of successful treatment. Characteristics and survival were reviewed in all patients treated between 19932013. METHODS: Hospital databases revealed 134 patients with pathologically-proven thymic tumour. Follow-up (median 63 months) was through patient notes and telephone contact with general practitioner. RESULTS: Patients were classified in Masaoka Koga stages: I: 50 (37%); Ila: 14 (10%); lib: 14 (10%); III: 27 (20%); IVa: 19 (14%); IVb: 4 (3%); unknown: 6 (5%). According to WHO classification, pathological subtypes were A: 19 (14%); AB: 25 (19%); B1: 21 (16%); B2: 31 (23%); B3: 15 (11%); thymic carcinoma: 23 (17%). Parathymic syndromes were diagnosed in 45 patients: myasthenia gravis (84%); pure red-cell aplasia (4%); hypogammaglobulinemia (2%); and others. 124 patients (93%) underwent surgery with complete resection in 104 (84%). Surgical approach was: sternotomy: 79; thoracotomy: 35; cervicotomy: 2; other/unknown: 8. In 73 patients (59%) no biopsy was taken prior to surgical resection, 25 were treated with induction chemotherapy, 36 received adjuvant radiotherapy. Hospital mortality was 0.81%. 35 patients died during follow-up (13 of tumour or treatment-related causes). Overall and recurrence-free survival at 5, 10, and 15 years were 86%; 64%; 47% and 67%; 49%; and 31%, respectively and were significantly (p < 0.01) different according to Masaoka-Koga stage. There was a significant association between WHO classification and Masaoka-Koga stages I-IIa-IIb versus III-IVa-IVb (p < 0.01). CONCLUSIONS: Operability and complete resectability of thymic tumours in our experience is high resulting in prolonged overall and recurrence-free survival. Masaoka-Koga stage is an important predictor for survival and shows a significant association with WHO classification. PMID- 27384899 TI - The Development of an Electronic Portfolio for Postgraduate Surgical Training in Flanders. AB - BACKGROUND: Contemporary surgical postgraduate training is characterized by clear outcomes for the profession and an assessment program that shows that trainees master these outcomes. The tool used to collect assessment and feedback instruments is the portfolio, nowadays used in many countries worldwide. METHODS: The four Flemish surgical coordinators, together with experts from different universities, devised an electronic portfolio. This portfolio holds both the logbook, as imposed by the evaluation committee and assessment instruments used for the Master in Specialized Medicine. RESULTS: The e-portfolio is now used by a number of surgical trainees and has been approved by the evaluation committee. In 1015, all Flemish surgical trainees will be using one and the same e-portfolio. CONCLUSION: Although the e-portfolio for surgical training has now been devised and accepted by all major parties involved, a lot of work has to be done to implement the instrument. As resident duty hours show no improvement on education in surgery (but rather a perception of worsened education) surgery training is fazing huge challenges. PMID- 27384898 TI - Survival and Prognostic Factors of Anaplastic Thyroid Carcinoma. AB - BACKGROUND: Anaplastic thyroid carcinoma (ATC) is relatively rare and represents one of the most aggressive tumours with poor prognosis, despite therapy. The aim of the study was to analyse demographic and clinical characteristics of ATC patients, and to identify survival rates and prognostic factors. METHODS: In a retrospective study (1995-2005) ATC was found in 150 patients treated at our institution. Survival was calculated by Kaplan-Meier curve and log-rank test. Potential prognostic factors affecting survival were compared by Cox univariate and multivariate analyses. RESULTS: Mean survival time was 56 weeks; median survival time was 16 weeks and 1 and 5-year survival were 17% and 8%. More than 10% died during the first month and 50% died up to the fourth month. Multivariate analysis showed that age, goitre and surgery were independent prognostic factors of survival in all ATC patients. Among operated patients, the extent of tumour resection, distant metastasis and multicentricity were independent prognostic risk factors of survival. Postoperative radiotherapy was a protective factor. CONCLUSIONS: There is still no successful treatment of ATC that can guarantee long term survival. Younger patients with pre-existing goitre, who undergo complete resection of unilocular early stage ATC without distant metastasis and with postoperative external radiotherapy, stand a better chance of long-term survival. PMID- 27384900 TI - Hydronephrosis in Acute Uncomplicated Appendicitis. AB - BACKGROUND: Right-sided hydronephrosis as a sign of appendicitis occurs rarely in the literature. To our knowledge, this is the first published account of the occurrence of right-sided hydronephrosis as a result of uncomplicated appendicitis. CASE DESCRIPTION: We describe a 15 year old patient referred to the emergency department with suspected appendicitis. Additional ultrasound examination showed a right-sided hydronephrosis. This finding was discussed with the urologist who noted the hydronephrosis as a chance finding. Because of persistent clinical suspicion of appendicitis, a diagnostic laparoscopy was performed. A retrocaecal appendicitis with secondary hydronephrosis was found. CONCLUSION: Right-sided hydronephrosis may be a sign of acute uncomplicated (retrocaecal) appendicitis. It is important to keep sight of these findings, especially in view of the emphasis on imaging techniques in the current Dutch guideline on appendicitis. PMID- 27384901 TI - Conservative Treatment of Spontaneous Dissection of the Subclavian Artery. AB - Dissection of the subclavian artery usually occurs as a result of trauma, endovascular interventions or connective tissue disorders. Only rarely has it been described occurring spontaneously. The treatment can be endovascular, open surgery, conservative or a combination of the above. There are no guidelines. The best approach is the one tailored to the lesion itself. This case presents a 73 year-old man with a tiresome and heavy feeling in the right arm. He was diagnosed having a spontaneous dissection of the right subclavian artery, accompanied by a complete occlusion more distally. Because of the relatively minor symptoms he was treated conservatively using anticoagulants. After 6 months of treatment there was complete revascularisation with good pulsations at the right wrist. PMID- 27384902 TI - Gastric Bypass for Morbid Obesity in a Patient with Situs Inversus Totalis. AB - The aim of this case report is to outline the challenge and the feasibility of laparoscopic gastric bypass in a patient with situs inversus totalis. Situs inversus totalis does not seem to be a contraindication for laparoscopic surgery. PMID- 27384903 TI - Possible Familial Presentation in Two Siblings with Carotid Fibromuscular Dysplasia. AB - Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory vascular disease which can affect the cervical, renal and visceral arteries. Here we report on two sisters diagnosed with carotid FMD at the same age, presenting with similar symptoms of pulsating tinnitus. The familial presentation of this rare disorder attracted our attention and was suggestive of a genetic etiology. Conservative treatment with aspirin was initiated. Carotid FMD is a rare disorder of which the exact pathophysiology is not known. A review of the literature on the clinical presentation, diagnosis and management is presented. In addition possible etiological factors and the genetic nature of the disease are discussed. PMID- 27384904 TI - Postradiation Dermatofibrosarcoma Protuberans: Case Report and Literature Review. AB - Radiotherapy has long been known to induce soft tissue sarcomas. However, there are only six cases of post-radiation dermatofibrosarcoma protuberans (DFSP) reported in the literature, and no case in Asians has been reported so far. Herein, we report a case of DFSP, confirmed by immunohistochemistry, which developed on the old scar at the irradiated right chest wall of an Asian woman. We performed a radical surgical excision of the lesion and covered the defect with latissimus dorsi island myocutaneous flap followed the surgical treatment. 12 months postoperatively, the patient leads a good result without signs of recurrence. PMID- 27384905 TI - Vesalius' Experience with Aortic Aneurysms. PMID- 27384906 TI - Leiomyosarcoma of the Inferior Vena Cava Level II Including Both Renal Veins: Surgical Approach. AB - A 66 years old male developping an acute lower right limb oedema due to an extended venous thrombosis of the common femoral and iliac veins was diagnosed to have a leiomyosarcoma of the inferior vena cava (IVC) involving both renal veins. The characteristics and management of this level II IVC leiomyosarcoma are discussed with particular attention to the renal vein reconstruction and neo adjuvant therapy. PMID- 27384907 TI - Don't dismiss pioglitazone on basis of uncertain risk. PMID- 27384908 TI - Development of Gas Chromatographic Mass Spectrometry. AB - Gas chromatographic mass spectrometry is now widely used for the quantitation and identification of organic compounds in almost any imaginable sample. These applications include the measurement of chlorinated dioxins in soil samples, the identification of illicit drugs in human blood, and the quantitation of accelerants in arson investigations, to name just a few. How did GC/MS get so popular? It turns out that it required parallel developments in mass spectrometry, gas chromatography, and computing and that no one person "invented" the technique. This Perspective traces this history from the 1950s until today. PMID- 27384910 TI - Kinetic Resolution of 2H-Azirines by Asymmetric Imine Amidation. AB - Highly efficient kinetic resolution of 2H-azirines by an asymmetric imine amidation was achieved in the presence of a chiral N,N'-dioxide/Sc(III) complex, thus providing a promising method to obtain the enantioenriched 2H-azirine derivatives and protecting-group free aziridines at the same time. It is rare to find an example of N1 of an oxindole participating in a reaction over C3. Moreover, chiral 2H-azirines were stereospecifically transformed into an unprotected aziridine and alpha-amino ketone. PMID- 27384909 TI - Bisphenol A affects early bovine embryo development and metabolism that is negated by an oestrogen receptor inhibitor. AB - Increasing evidence supports an association between exposure to endocrine disruptors, such as the xenoestrogen bisphenol A (BPA), a commonly used plasticiser, and the developmental programming of offspring health. To date however animal studies to investigate a direct causal have mainly focussed on supra-environmental BPA concentrations, without investigating the effect on the early embryo. In this study we investigated the effect of acute BPA exposure (days 3.5 to 7.5 post-fertilisation) at environmentally relevant concentrations (1 and 10 ng/mL) on in vitro bovine embryo development, quality and metabolism. We then examined whether culturing embryos in the presence of the oestrogen receptor inhibitor fulvestrant could negate effects of BPA and 17beta-oestradiol (E2). Exposure to BPA or E2 (10 ng/mL) decreased blastocyst rate and the percentage of transferrable quality embryos, without affecting cell number, lineage allocation or metabolic gene expression compared to untreated embryos. Notably, blastocysts exposed to BPA and E2 (10 ng/mL) displayed an increase in glucose consumption. The presence of fulvestrant however negated the adverse developmental and metabolic effects, suggesting BPA elicits its effects via oestrogen-mediated pathways. This study demonstrates that even acute exposure to an environmentally relevant BPA concentration can affect early embryo development and metabolism. These may have long-term health consequences on an individual. PMID- 27384911 TI - Walking activity during daily living in children with myelomeningocele. AB - PURPOSE: To quantify the walking activity of children with myelomeningocele during daily living. METHOD: Walking activity was measured using a StepWatch activity monitor over one week in 47 children with myelomeningocele (27 males; 9 years 11 months SD 2 years 7 months; 18 sacral, 9 low lumbar, 20 mid-high lumbar) and seven children with typical development (5 males; 11 years 1 month SD 1 year 11 months) in a prospective, cross-sectional study. Average total steps per day, number of steps and minutes spent at low, medium and high intensity stepping were evaluated. Groups were compared using t-tests and chi-squared tests with Bonferroni post-hoc adjustment. RESULTS: Children with sacral and low lumbar myelomeningocele exhibited no significant differences in demographic characteristics or walking performance compared to typically developing children. Children with mid-high lumbar myelomeningocele exhibited higher BMI percentile than the control group (p = 0.04) and took fewer total steps per day than all other groups (p <= 0.04). Children with mid-high lumbar myelomeningocele also spent significantly less time taking steps at all intensity levels, particularly medium-intensity, than the sacral and low lumbar groups (p <= 0.04). CONCLUSIONS: Children with sacral and low lumbar myelomeningocele had walking performance similar to typically developing children despite a common need for braces and assistive devices. Children with mid-high lumbar myelomeningocele were less active, which may lead to heightened risk for secondary health conditions in addition to those associated with myelomeningocele. Implications for Rehabilitation Obesity, muscle weakening and disuse osteoporosis are issues for those with myelomeningocele, all of which are affected by walking activity. Understanding walking activity and intensity in children and adolescents with myelomeningocele may aid in developing focused rehabilitation interventions and strategies. Real world walking activity as an objective and quantified measure has the potential to help guide therapists and surgeons to more effective treatments. PMID- 27384913 TI - Pfannenstiel laparoendoscopic reduced-port radical nephrectomy. AB - INTRODUCTION: We previously reported cases of laparoendoscopic single-site nephrectomy performed through an umbilical or pararectal incision. To improve cosmesis and operability, we performed three Pfannenstiel laparoendoscopic reduced-port nephrectomies. MATERIALS AND SURGICAL TECHNIQUE: In the first case, a GelPOINT access was placed through a 2-cm umbilical incision, and two additional 3-mm trocars were inserted. The specimen was extracted through a 4-cm Pfannenstiel incision. In the second and third cases, a GelPOINT access was placed through a 5-cm Pfannenstiel incision, and two additional 3-mm trocars were inserted. The specimens were extracted without additional skin incisions. In all cases, the endoscope and vessel-sealing device were inserted through the GelPOINT access. We used 3-mm scissors, dissecting forceps, and bipolar forceps. DISCUSSION: The operating time and estimated blood loss were 228, 280, and 155 min and 10, 410, and 5 mL, respectively. There were no intraoperative or postoperative complications. The 3-mm forceps showed similar efficacy as the conventional 5-mm forceps. Therefore, a Pfannenstiel reduced-port nephrectomy using 3-mm working trocars is a safe and feasible procedure with good cosmesis. PMID- 27384912 TI - Sulfur mustard inhalation: mechanisms of injury, alteration of coagulation, and fibrinolytic therapy. AB - Acute lung injury due to sulfur mustard (SM) inhalation causes the formation of airway fibrin casts that obstruct airways at multiple levels, leading to acute respiratory failure and death. These pathophysiological effects are seen in rodent models of acute SM vapor inhalation, as well as in human victims of acute SM inhalation. In rat models, the initial steps in activation of the coagulation system at extravascular sites depend on tissue factor (TF) expression by airway cells, especially in the microparticle fraction, and these effects can be inhibited by TF pathway inhibitor protein. Not only does the procoagulant environment of the acutely injured lung contribute to airway cast formation, but these lesions persist in airways because of the activation of multiple antifibrinolytic pathways, including plasminogen activator inhibitor-1, thrombin activatable fibrinolysis inhibitor, and alpha2-antiplasmin. Airway administration of tissue plasminogen activator can overwhelm these effects and save lives by preventing fibrin-dependent airway obstruction, gas-exchange abnormalities, and respiratory failure. In human survivors of SM inhalation, fibrotic processes, including bronchiolitis obliterans and interstitial fibrosis of the lung, are among the most disabling chronic lesions. Antifibrotic therapies may prove useful in preventing either or both of these forms of chronic lung damage. PMID- 27384914 TI - Relationship between tissue tension and thermal diffusion to peripheral tissue using an energy device. AB - The aim of the study was to assess the relationship between tissue tension and thermal diffusion to peripheral tissues using an electric scalpel, ultrasonically activated device, or a bipolar sealing system. The mesentery of pigs was excised with each energy device (ED) at three tissue tensions (0, 300, 600 g). The excision time and thermal diffusion area were monitored with thermography, measured for each ED, and then histologically examined. Correlations between tissue tension and thermal diffusion area were examined. The excision time was inversely correlated with tissue tension for all ED (electric scalpel, r = 0.718; ultrasonically activated device, r = 0.949; bipolar sealing system, r = 0.843), and tissue tension was inversely correlated with the thermal diffusion area with the electric scalpel (r = 0.718) and bipolar sealing system (r = 0.869). Histopathologically, limited deep thermal denaturation occurred at a tension of 600 g with all ED. We conclude that thermal damage can be avoided with adequate tissue tension when any ED is used. PMID- 27384916 TI - MicroRNA and venous thrombosis. PMID- 27384915 TI - The More the Tubular: Dynamic Bundling of Actin Filaments for Membrane Tube Formation. AB - Tubular protrusions are a common feature of living cells, arising from polymerization of stiff protein filaments against a comparably soft membrane. Although this process involves many accessory proteins in cells, in vitro experiments indicate that similar tube-like structures can emerge without them, through spontaneous bundling of filaments mediated by the membrane. Using theory and simulation of physical models, we have elaborated how nonequilibrium fluctuations in growth kinetics and membrane shape can yield such protrusions. Enabled by a new grand canonical Monte Carlo method for membrane simulation, our work reveals a cascade of dynamical transitions from individually polymerizing filaments to highly cooperatively growing bundles as a dynamical bottleneck to tube formation. Filament network organization as well as adhesion points to the membrane, which bias filament bending and constrain membrane height fluctuations, screen the effective attractive interactions between filaments, significantly delaying bundling and tube formation. PMID- 27384917 TI - Partial In Vitro Reconstitution of an Orphan Polyketide Synthase Associated with Clinical Cases of Nocardiosis. AB - Although a few well-characterized polyketide synthases (PKSs) have been functionally reconstituted in vitro from purified protein components, the use of this strategy to decode "orphan" assembly line PKSs has not been described. To begin investigating a PKS found only in Nocardia strains associated with clinical cases of nocardiosis, we reconstituted in vitro its five terminal catalytic modules. In the presence of octanoyl-CoA, malonyl-CoA, NADPH, and S-adenosyl methionine, this pentamodular PKS system yielded unprecedented octaketide and heptaketide products whose structures were partially elucidated using mass spectrometry and NMR spectroscopy. The PKS has several notable features, including a "split, stuttering" module and a terminal reductive release mechanism. Our findings pave the way for further analysis of this unusual biosynthetic gene cluster whose natural product may enhance the infectivity of its producer strains in human hosts. PMID- 27384918 TI - Functional and molecular evidence for heteromeric association of P2Y1 receptor with P2Y2 and P2Y4 receptors in mouse granulocytes. AB - BACKGROUND: All hematopoietic cells express P2 receptors, however pharmacological characteristics such as expression and affinity in granulocytes are unknown. METHODS: Pharmacological characteristics of P2 receptors were evaluated by Ca(2+) measurements using Fura-2 fluorophore. P2 receptors expression were analyzed by flow cytometry and RT-PCR. P2 interaction were shown by coimmunoprecipitation, western blotting and FRET. RESULTS: Granulocytes were responsive to P2Y agonists, whereas P2X agonists were ineffective. Ca(2+) increase, elicited by ADP and UTP was dependent on intracellular stocks and sensitive to G-coupled receptor inhibition. Moreover, MRS2179, a specific antagonist of the P2Y1 receptor, abolished ADP response. Interestingly, ADP and UTP exhibited full heterologous desensitization, suggesting that these agonists interact with the same receptor. The heteromeric association between P2Y1 receptor and the P2Y2 and P2Y4 receptors was shown by immunoprecipitation and FRET analysis. CONCLUSION: Clear evidence of heteromeric association of P2Y receptors was found during the evaluation of P2 receptors present in mice granulocytes, which could impact in the classical pharmacology of P2Y receptors in granulocytes. PMID- 27384921 TI - Intermolecular Hydropyridylation of Unactivated Alkenes. AB - A general method for the hydropyridylation of unactivated alkenes is described. The transformation connects metal-mediated hydrogen atom transfer to alkenes and Minisci addition reactions. The reaction proceeds under mild conditions with high site-selectivities and allows for the construction of tertiary and quaternary centers from simple alkene starting materials. PMID- 27384919 TI - Homebound Patient and Caregiver Perceptions of Quality of Care in Home-Based Primary Care: A Qualitative Study. AB - OBJECTIVES: To assess patient and caregiver perceptions of what constitutes quality care in home-based primary care (HBPC). DESIGN: Cross-sectional qualitative design; semistructured interview study. SETTING: Academic home-based primary care program. PARTICIPANTS: Homebound patients (n = 13) and 10 caregivers (n = 10) receiving HBPC. MEASUREMENTS: Semistructured interviews explored experiences with a HBPC program and perceptions of quality care. Interviews were audio-recorded and transcribed. Qualitative content analysis was performed to identify major themes. RESULTS: Five major themes emerged related to participant perceptions of quality care: access, affordability, competency, care coordination, goal attainment. Participants felt that reliable, consistent access provided "peace of mind" and reduced hospital and emergency department use. Insurance coverage of program costs and coordinated care provided by an interdisciplinary team were positively regarded. Interpersonal skills and technical abilities of providers influenced patient perception of provider competency. Assessing and helping patients attain care goals contributed to a perception of quality care. CONCLUSION: Patients and caregivers associate high quality HBPC with around-the-clock access to affordable interdisciplinary providers with strong interpersonal skills and technical competency. These results expand on prior research and are concordant with HBPC goals of around-the clock access to multidisciplinary teams with the goals of reduced emergency department and hospital use. HBPC programs should be structured to optimize access, affordability, coordinated care, and goal ascertainment and alignment. Quality indicators should be created and validated with these patient and caregiver views of care quality in mind. PMID- 27384924 TI - [Software-based visualization of patient flow at a university eye clinic]. AB - OBJECTIVE: This article presents a method for visualization and navigation of patient flow in outpatient eye clinics with a high level of complexity. MATERIAL AND METHODS: A network-based software solution was developed targeting long-term process optimization by structural analysis and temporal coordination of process navigation. RESULTS: Each examination unit receives a separate waiting list of patients in which the patient flow for every patient is recorded in a timeline. Time periods and points in time can be executed by mouse clicks and the desired diagnostic procedure can be entered. Recent progress in any of these diagnostic requests, as well as a variety of information on patient progress are collated and drawn into the corresponding timeline which can be viewed by any of the personnel involved. The software called TimeElement has been successfully tested in the practical implemenation for several months. As an example the patient flow regarding time stamps of defined events for intravitreous injections on 250 patients was recorded and an average attendance time of 169.71 min was found, whereby the time was also automatically recorded for each individual stage. CONCLUSION: Recording of patient flow data is a fundamental component of patient flow management, waiting time reduction, patient flow navigation with time and coordination in particular regarding timeline-based visualization for each individual patient. Long-term changes in process management can be planned and evaluated by comparing patient flow data. As using the software itself causes structural changes within the organization, a questionnaire is being planned for appraisal by the personnel involved. PMID- 27384925 TI - Theoretical study on photooxidation mechanism of ruthenium complex [Ru(II)-(bpy)2 (TMBiimH2 )](2+) with molecular oxygen. AB - Photoinduced reactions of ruthenium complexes with molecular oxygen have attracted a lot of experimental attention; however, the reaction mechanism remains elusive. In this work, we have used the density functional theory method to scrutinize the visible-light induced photooxidation mechanism of the ruthenium complex [Ru(II)-(bpy)2 (TMBiimH2 )](2+) (bpy: 2, 2-bipyridine and TMBiimH2 : 4, 5, 4, 5-tetramethyl-2, 2-biimidazole) initiated by the attack of molecular oxygen. The present computational results not only explain very well recent experiments, also provide new mechanistic insights. We found that: (1) the triplet energy transfer process between the triplet molecular oxygen and the metal-ligand charge transfer triplet state of the ruthenium complex, which leads to singlet molecular oxygen, is thermodynamically favorable; (2) the singlet oxygen addition process to the S0 ruthenium complex is facile in energy; (3) the chemical transformation from endoperoxide to epidioxetane intermediates can be either two- or one-step reaction (the latter is energetically favored). These findings contribute important mechanistic information to photooxidation reactions of ruthenium complexes with molecular oxygen. (c) 2016 Wiley Periodicals, Inc. PMID- 27384922 TI - Glycoform-independent prion conversion by highly efficient, cell-based, protein misfolding cyclic amplification. AB - Prions are formed of misfolded assemblies (PrP(Sc)) of the variably N glycosylated cellular prion protein (PrP(C)). In infected species, prions replicate by seeding the conversion and polymerization of host PrP(C). Distinct prion strains can be recognized, exhibiting defined PrP(Sc) biochemical properties such as the glycotype and specific biological traits. While strain information is encoded within the conformation of PrP(Sc) assemblies, the storage of the structural information and the molecular requirements for self perpetuation remain uncertain. Here, we investigated the specific role of PrP(C) glycosylation status. First, we developed an efficient protein misfolding cyclic amplification method using cells expressing the PrP(C) species of interest as substrate. Applying the technique to PrP(C) glycosylation mutants expressing cells revealed that neither PrP(C) nor PrP(Sc) glycoform stoichiometry was instrumental to PrP(Sc) formation and strainness perpetuation. Our study supports the view that strain properties, including PrP(Sc) glycotype are enciphered within PrP(Sc) structural backbone, not in the attached glycans. PMID- 27384923 TI - Expression of ERAP2 and LST1 is increased before start of therapy in rheumatoid arthritis patients with good clinical response to glucocorticoids. AB - OBJECTIVES: Glucocorticoids (GC) remain a cornerstone of rheumatoid arthritis (RA) therapy, although a third of patients do not respond adequately. In order to find potential predictors for clinical response, the gene expression profile of CD4+T-cells as important players in the pathogenesis of RA was analysed before pulse therapy with 1000 mg methylprednisolone. METHODS: Patients were treated with 3x1000 mg methylprednisolone in 5 days; hereafter response was determined by the European League Against Rheumatism (EULAR) response criteria. Before start of treatment, CD4+T-cells (and CD14+monocytes) were separated by MACS sorting. Labelled cRNA from CD4+T-cells from 5 responders and 5 non-responders was hybridised to Agilent 4x44K microarray chips and differentially expressed genes were identified via mixed-model analysis of variance based on permutation-based false discovery rates. Selected genes were validated by quantitative real-time PCR (qPCR). RESULTS: Four genes were significantly increased in CD4+T-cells of GC responders; expression of ERAP2 (endoplasmic reticulum aminopeptidase 2), LST1 (leucocyte-specific transcript 1) and FAM26F (Family With Sequence Similarity 26, Member F) was confirmed by quantitative PCR (qPCR); their expression was inversely correlated with DAS28 at day 5 (LST1 and FAM26F p<0.05; ERAP2: p=0.07). Elevated expression of ERAP2 was also detected by qPCR in CD14+monocytes and after 24 hours in both cell types (all p<0.02). CONCLUSIONS: The increased expression of ERAP2, LST1 and FAM26F in GC-responders before therapy warrants further investigation into their role as potential predictors for the response to GC, and in the inflammatory process of RA. PMID- 27384926 TI - Benchmark Calculations of Energetic Properties of Groups 4 and 6 Transition Metal Oxide Nanoclusters Including Comparison to Density Functional Theory. AB - The heats of formation and the normalized clustering energies (NCEs) for the group 4 and group 6 transition metal oxide (TMO) trimers and tetramers have been calculated by the Feller-Peterson-Dixon (FPD) method. The heats of formation predicted by the FPD method do not differ much from those previously derived from the NCEs at the CCSD(T)/aT level except for the CrO3 nanoclusters. New and improved heats of formation for Cr3O9 and Cr4O12 were obtained using PW91 orbitals instead of Hartree-Fock (HF) orbitals. Diffuse functions are necessary to predict accurate heats of formation. The fluoride affinities (FAs) are calculated with the CCSD(T) method. The relative energies (REs) of different isomers, NCEs, electron affinities (EAs), and FAs of (MO2)n (M = Ti, Zr, Hf, n = 1-4) and (MO3)n (M = Cr, Mo, W, n = 1-3) clusters have been benchmarked with 55 exchange-correlation density functional theory (DFT) functionals including both pure and hybrid types. The absolute errors of the DFT results are mostly less than +/-10 kcal/mol for the NCEs and the EAs and less than +/-15 kcal/mol for the FAs. Hybrid functionals usually perform better than the pure functionals for the REs and NCEs. The performance of the two types of functionals in predicting EAs and FAs is comparable. The B1B95 and PBE1PBE functionals provide reliable energetic properties for most isomers. Long range corrected pure functionals usually give poor FAs. The standard deviation of the absolute error is always close to the mean errors, and the probability distributions of the DFT errors are often not Gaussian (normal). The breadth of the distribution of errors and the maximum probability are dependent on the energy property and the isomer. PMID- 27384928 TI - Aging of Zerovalent Iron in Synthetic Groundwater: X-ray Photoelectron Spectroscopy Depth Profiling Characterization and Depassivation with Uniform Magnetic Field. AB - Scanning electron microscopy (SEM), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS) depth profiling were employed to characterize the aged zerovalent iron (AZVI) samples incubated in synthetic groundwater. The AZVI samples prepared under different conditions exhibited the passive layers of different morphologies, amounts, and constituents. Owing to the accumulation of iron oxides on their surface, all the prepared AZVI samples were much less reactive than the pristine ZVI for Se(IV) removal. However, the reactivity of all AZVI samples toward Se(IV) sequestration could be significantly enhanced by applying a uniform magnetic field (UMF). Moreover, the flux intensity of UMF necessary to depassivate an AZVI sample was strongly dependent on the properties of its passive layer. The UMF of 1 mT was strong enough to restore the reactivity of the AZVI samples with Fe3O4 as the major constituent of the passive film or with a thin layer of alpha-Fe2O3 and gamma-FeOOH in the external passive film. The flux intensity of UMF necessary to depassivate the AZVI samples would increase to 2 mT or even 5 mT if the AZVI samples were covered with passive films being thicker, denser, and contained more gamma-FeOOH and alpha-Fe2O3. Furthermore, increasing the flux intensity of UMF facilitated the reduction of Se(IV) to Se(0) by AZVI samples. PMID- 27384927 TI - Development of enhancing agglutination reaction using gold nanoparticle for pre transfusion testing. AB - OBJECTIVES: To explore an alternative way for antibody detection testing, the examination of gold nanoparticle solution for enhancing unexpected antibodies for pre-transfusion testing was investigated. BACKGROUND: Exposure of foreign antigens on red blood cells from transfusion can trigger the immune system to produce unexpected antibodies. This immunological response may cause the complication to future transfusion. For detection of unexpected antibodies, the antibody screening test is performed approximately 30-60 min. To reduce turnaround time, enhancing reagent, low-ionic strength solution (LISS), is widely used. However, cost of enhancing reagent is an issue which has concerned in resource limited countries. Gold nanoparticle solution can increase red blood cells agglutination reaction. To solve this issue, study of gold nanoparticle solution was investigated. METHODS: Samples were performed comparing between LISS and gold nanoparticle solution at antiglobulin phase. After reading the agglutination reaction, supernatants were collected and measured at the optical density at 760 nm by spectrophotometer. RESULTS: The optical density in the tube of gold nanoparticle solution was higher than in the tube of 2-5% cell suspension and monoclonal antibody. It has been observed that gold nanoparticle solution enhanced the reaction of agglutination 98% while LISS enhanced the agglutination only 60.8%. Employing a commercially available enhancing reagent, parallel samples confirmed results providing validation of the assay. It approximately costs $1 US dollars compared to $30 for a commercially available reagent. CONCLUSIONS: The low cost and yet effective time-consuming test for antibody screening is a practical and viable solution alternative way for performing in antibody screening test in resource limited countries. PMID- 27384929 TI - Tobacco control in Africa. PMID- 27384930 TI - Alzheimer Therapy: Photoactive g-C3 N4 Nanosheets for Light-Induced Suppression of Alzheimer's beta-Amyloid Aggregation and Toxicity (Adv. Healthcare Mater. 13/2016). AB - The accumulation of beta-amyloid peptides and their aggregation in brain is a hallmark of Alzheimer's disease. On page 1560 C. B. Park and co-workers describe a strong suppression effect of graphitic carbon nitride (g-C3 N4 ) toward beta amyloid aggregation under light-illumination. Photoexcited g-C3 N4 generates reactive oxygen species and blocks further beta-amyloid aggregation by impacting conformational structure of beta-amyloid, rendering it a promising material for Alzheimer therapy. PMID- 27384932 TI - Tissue Engineering: Nano-Enabled Approaches for Stem Cell-Based Cardiac Tissue Engineering(Adv. Healthcare Mater. 13/2016). AB - On page 1533 M. Nikkhah and co-workers review tissue engineering strategies in the treatment of cardiac diseases with emphasis on the use of nanoenabled approaches (e.g. nanoparticles, nanotopographies) in combination with stem cells for regeneration and repair of injured myocardium upon myocardial infarction. PMID- 27384933 TI - Tissue Engineering: Mechanocompatible Polymer-Extracellular-Matrix Composites for Vascular Tissue Engineering (Adv. Healthcare Mater. 13/2016). AB - Heparinized mechanocompatible polymer-extracellular matrix (ECM) composites to improve vascular graft performance are presented by J. A. Wertheim, G. A. Ameer, and co-workers on page 1594. Polymer-coated ECM is visualized by the purple color. The composite vascular graft reduced intimal hyperplasia in a rodent model, revealed by alpha-smooth muscle actin staining (green). The method shows promise for tissue engineering where immobilization of bioactive molecules is desirable. PMID- 27384934 TI - 3D Tissue Culturing: Tissue in Cube: In Vitro 3D Culturing Platform with Hybrid Gel Cubes for Multidirectional Observations (Adv. Healthcare Mater. 13/2016). AB - An in vitro 3D culturing platform enabling multidirectional observations of 3D biosamples is presented by M. Hagiwara and co-workers on page 1566. 3D recognition of a sample structure can be achieved by facilitating multi directional views using a standard microscope without a laser system. The cubic platform has the potential to promote 3D culture studies, offering easy handling and compatibility with commercial culture plates at a low price tag. PMID- 27384936 TI - Dual-Energy CT of Incidental Findings in the Abdomen: Can We Reduce the Need for Follow-Up Imaging? AB - OBJECTIVE: The purpose of this article is to review the added value of dual energy CT for characterization of incidental lesions discovered during routine abdominal CT. CONCLUSION: Dual-energy CT allows acquisition of virtual unenhanced images, iodine maps, and virtual monochromatic images, all of which can aid in characterizing incidental lesions at the time of detection. Virtual unenhanced images and iodine maps are used for assessment of enhancement of incidental lesions, which can help differentiate suspicious enhancing lesions from benign nonenhancing lesions. Virtual monochromatic images can be obtained at low energy to improve conspicuity and detection of subtle lesions. Routine use of dual energy CT may eliminate the need for additional imaging in the workup of some of these incidental lesions. PMID- 27384937 TI - Imaging Spatiotemporal Activities of ZAP-70 in Live T Cells Using a FRET-Based Biosensor. AB - The zeta-chain-associated protein kinase 70 kDa (ZAP-70), a member of the spleen tyrosine kinase (Syk) family, plays an essential role in early T cell receptor (TCR) signaling. Defects in ZAP-70 lead to impaired thymocyte development and peripheral T cell activation. To better understand its activation dynamics and regulation, we visualized ZAP-70 activities in single live T cells with a Forster resonance energy transfer (FRET)-based biosensor, which was designed for probing kinase activities of the Syk family. We observed in Jurkat E6.1 T cells rapid and specific FRET changes following anti-CD3 stimulation and subsequent piceatannol inhibition. The initiation of ZAP-70 activation was prompt (within 10 s) and correlates with the accompanied intracellular calcium elevation, as revealed by simultaneous imaging of the biosensor and calcium. Different from the previously reported ZAP-70 activation in the immunological synapse and the opposite pole (anti-synapse), we have observed rapid and sustained ZAP-70 activation only at the synapse with superantigen-pulsed Raji B cells. Furthermore, ZAP-70 signaling was impaired by cholesterol depletion, further supporting the importance of membrane organization in TCR signaling. Together our results provide a direct characterization of the spatiotemporal features of ZAP-70 activity in real time at subcellular levels. PMID- 27384938 TI - Clearance of Subarachnoid Hemorrhage from the Cerebrospinal Fluid in Computational and In Vitro Models. AB - Subarachnoid hemorrhage (SAH) mostly occurs following the rupture of cerebral aneurysm causing blood to leak into the cranial subarachnoid space (SAS). Hemorrhage volume has been linked to the development of secondary vasospasm. Therefore, eliminating blood contaminants from the cerebrospinal fluid (CSF) space after the initial hemorrhage could improve patient outcomes and prevent the development of vasospasm. A number of clinical trials demonstrate that lumbar drainage effectively clears hemorrhagic debris from the cranial compartment. The benefits of optimal lumbar drainage rate and patient orientation are difficult to determine by trial-and-error in live patients, because of the invasive nature, limited subject availability and ethical considerations. Therefore, there is a lack of consensus about clinical guidelines for the use of continuous lumbar drainage following the ictus of SAH. A realistic bench-top model which reproduces the anatomy and CSF dynamics of the human central nervous system (CNS) was built to experimentally study contaminant clearance scenarios under lumbar drainage. To mimic a hemorrhagic event, porcine blood was injected at the basal cistern level of the bench-top model and the efficacy of lumbar drains was assessed experimentally for different drainage rates and patient orientations. In addition, the efficacy of blood clearance was predicted with a computational fluid dynamics (CFD) model. Bench-top experiments and CFD simulations identify body position and drainage rates as key parameters for effective blood clearance. The study findings suggest the importance of treatment in upright position to maximize contaminant diversion from the cranial CSF compartment. The bench-top CNS model together with the validated CFD predictions of lumbar drainage systems can serve to optimize subject-specific treatment options for SAH patients. PMID- 27384939 TI - Design and Fabrication of Complex Scaffolds for Bone Defect Healing: Combined 3D Plotting of a Calcium Phosphate Cement and a Growth Factor-Loaded Hydrogel. AB - Additive manufacturing enables the fabrication of scaffolds with defined architecture. Versatile printing technologies such as extrusion-based 3D plotting allow in addition the incorporation of biological components increasing the capability to restore functional tissues. We have recently described the fabrication of calcium phosphate cement (CPC) scaffolds by 3D plotting of an oil based CPC paste under mild conditions. In the present study, we have developed a strategy for growth factor loading based on multichannel plotting: a biphasic scaffold design was realised combining CPC with VEGF-laden, highly concentrated hydrogel strands. As hydrogel component, alginate and an alginate-gellan gum blend were evaluated; the blend exhibited a more favourable VEGF release profile and was chosen for biphasic scaffold fabrication. After plotting, two-step post processing was performed for both, hydrogel crosslinking and CPC setting, which was shown to be compatible with both materials. Finally, a scaffold was designed and fabricated which can be applied for testing in a rat critical size femur defect. Optimization of CPC plotting enabled the fabrication of highly resolved structures with strand diameters of only 200 um. Micro-computed tomography revealed a precise strand arrangement and an interconnected pore space within the biphasic scaffold even in swollen state of the hydrogel strands. PMID- 27384940 TI - Effects of Chemically Doped Bioactive Borate Glass on Neuron Regrowth and Regeneration. AB - Peripheral nerve injuries present challenges to regeneration. Currently, the gold standard for nerve repair is an autograft that results in another region of the body suffering nerve damage. Previously, bioactive borate glass (BBG) has been studied in clinical trials to treat patients with non-healing wounds, and we have reported that BBG is conducive for soft tissue repair. BBG provides structural support, degrades in a non-cytotoxic manner, and can be chemically doped. Here, we tested a wide range of chemical compounds that are reported to have neuroprotective characteristics to promote regeneration of peripheral neurons after traumatic injury. We hypothesized that chemical dopants added in trace amounts to BBG would improve neuronal survival and neurite outgrowth from dorsal root ganglion (DRG) explants. We measured neurite outgrowth from whole DRG explants, and survival rates of dissociated neurons and support cells that comprise the DRG. Results show that chemically doped BBGs have differentially variable effects on neuronal survival and outgrowth, with iron, gallium, and zinc improving outgrowth of neurons, and iodine causing the most detriment to neurons. Because chemically doped BBGs support increased nerve regrowth and survival, they show promise for use in peripheral nerve regeneration. PMID- 27384941 TI - Protective Capacity of Ice Hockey Helmets against Different Impact Events. AB - In ice hockey, concussions can occur as a result of many different types of impact events, however hockey helmets are certified using a single injury scenario, involving drop tests to a rigid surface. The purpose of this study is to measure the protective capacity of ice hockey helmets for different impact events in ice hockey. A helmeted and unhelmeted Hybrid III headform were impacted simulating falls, elbow, shoulder and puck impacts in ice hockey. Linear and rotational acceleration and maximum principal strain (MPS) were measured. A comparison of helmeted and unhelmeted impacts found significant differences existed in most conditions (p < 0.05), however some shoulder and puck impacts showed no significant difference (p > 0.05). Impacts to the ice hockey helmet tested resulted in acceleration levels below reported ranges of concussion and TBI for falls up to 5 m/s, elbow collisions, and low velocity puck impacts but not for shoulder collisions or high velocity puck impacts and falls. The helmet tested reduced MPS below reported ranges of concussion and TBI for falls up to 5 m/s but not for the other impact events across all velocities and locations. This suggests that the ice hockey helmet tested is unable to reduce engineering parameters below reported ranges of concussion and TBI for impact conditions which do not represent a drop against a rigid surface. PMID- 27384943 TI - Controllable Molecule Transport and Release by a Restorable Surface-tethered DNA nanodevice. AB - In this paper, we report a novel surface-tethered DNA nanodevice that may present three states and undergo conformational changes under the operation of pH. Besides, convenient regulation on the electrode surface renders the construction and operation of this DNA nanodevice restorable. To make full use of this DNA nanodevice, ferrocene (Fc) has been further employed for the fabrication of the molecular device. On one hand, the state switches of the DNA nanodevice can be characterized conveniently and reliably by the obtained electrochemical signals from Fc. On the other hand, beta-cyclodextrin-ferrocene (beta-CD-Fc) host-guest system can be introduced by Fc, which functionalizes this molecular device. Based on different electrochemical behaviors of beta-CD under different states, this DNA nanodevice can actualize directional loading, transporting and unloading of beta-CD in nanoscale. Therefore, this DNA nanodevice bares promising applications in controllable molecular transport and release, which are of great value to molecular device design. PMID- 27384944 TI - Noncomplicated Excision of a Mobile Pedunculated Septal Hemangioma of the Left Ventricle. AB - BACKGROUND Cardiac tumors are quite rare, and differential diagnosis of them is challenging. CASE REPORT A young lady with a history of palpitations, dyspnea, and fatigue was proven by transthoracic echocardiography and cardiac magnetic resonance imaging to have a mobile left ventricular mass with rounded contour attached to the mid-part of the interventricular septum. The mass was approached via a posterior inter-atrial approach to avoid left ventriculotomy and provide adequate exposure to completely excise the tumor and control its pedicle with minimal cardiac trauma. Histological examination of the mass was diagnostic of capillary and sinusoidal hemangioma. CONCLUSIONS Complete excision of cardiac hemangioma is recommended once it is diagnosed, for histopathologic diagnosis and because of the possibility of serious complications. PMID- 27384942 TI - Multi-scale Modeling in Clinical Oncology: Opportunities and Barriers to Success. AB - Hierarchical processes spanning several orders of magnitude of both space and time underlie nearly all cancers. Multi-scale statistical, mathematical, and computational modeling methods are central to designing, implementing and assessing treatment strategies that account for these hierarchies. The basic science underlying these modeling efforts is maturing into a new discipline that is close to influencing and facilitating clinical successes. The purpose of this review is to capture the state-of-the-art as well as the key barriers to success for multi-scale modeling in clinical oncology. We begin with a summary of the long-envisioned promise of multi-scale modeling in clinical oncology, including the synthesis of disparate data types into models that reveal underlying mechanisms and allow for experimental testing of hypotheses. We then evaluate the mathematical techniques employed most widely and present several examples illustrating their application as well as the current gap between pre-clinical and clinical applications. We conclude with a discussion of what we view to be the key challenges and opportunities for multi-scale modeling in clinical oncology. PMID- 27384945 TI - Subdural hematoma cases identified through a Danish patient register: diagnosis validity, clinical characteristics, and preadmission antithrombotic drug use. AB - PURPOSE: This study aimed to assess the usefulness of Danish patient registers for epidemiological studies of subdural hematoma (SDH) and to describe clinical characteristics of validated cases. METHODS: Using a patient register covering a geographically defined area in Denmark, we retrieved hospital contacts recorded under SDH International Classification of Diseases version 10 codes S065 and I620 in 2000-2012. Neurosurgeons reviewed medical records of all potential cases. Based on brain scan results, verified cases were classified by SDH type (chronic SDH (cSDH) or acute SDH (aSDH)). Thirty-day mortality and preadmission antithrombotic drug use were established through linkage to population-based registers. We calculated the positive predictive value of the SDH code and compared mortality and preadmission antithrombotic drug use of cSDH with those of aSDH (age-adjusted and sex-adjusted odds ratio (OR), 95% confidence interval (95%CI)). RESULTS: We verified the diagnosis in 936 of 1185 identified patients. The positive predictive value was highest for hospital contacts with principal discharge diagnosis code S065 (96%) but was low for other contact types under code S065 (25-54%), and only moderate for patients recorded under code I620 (62%). cSDH represented 57% of verified cases, and aSDH the remaining 43%. cSDH differed markedly from aSDH with regard to a number of clinical characteristics, including a much lower mortality (OR 0.2, 95%CI 0.1-0.3). However, preadmission antithrombotic drug use did not vary by SDH type (OR 0.9, 95%CI 0.6-1.2). CONCLUSIONS: Danish patient registers are a useful resource for SDH studies. However, choice of International Classification of Diseases code markedly influences diagnostic validity. Distinction between cSDH and aSDH is not possible based on SDH diagnosis codes only. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27384946 TI - Hypopigmented Macules on the Face and Neck of a Man. PMID- 27384947 TI - Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame. AB - Reversion and spread of vaccine-derived poliovirus (VDPV) to cause outbreaks of poliomyelitis is a rare outcome resulting from immunisation with the live attenuated oral poliovirus vaccines (OPVs). Global withdrawal of all three OPV serotypes is therefore a key objective of the polio endgame strategic plan, starting with serotype 2 (OPV2) in April 2016. Supplementary immunisation activities (SIAs) with trivalent OPV (tOPV) in advance of this date could mitigate the risks of OPV2 withdrawal by increasing serotype-2 immunity, but may also create new serotype-2 VDPV (VDPV2). Here, we examine the risk factors for VDPV2 emergence and implications for the strategy of tOPV SIAs prior to OPV2 withdrawal. We first developed mathematical models of VDPV2 emergence and spread. We found that in settings with low routine immunisation coverage, the implementation of a single SIA increases the risk of VDPV2 emergence. If routine coverage is 20%, at least 3 SIAs are needed to bring that risk close to zero, and if SIA coverage is low or there are persistently "missed" groups, the risk remains high despite the implementation of multiple SIAs. We then analysed data from Nigeria on the 29 VDPV2 emergences that occurred during 2004-2014. Districts reporting the first case of poliomyelitis associated with a VDPV2 emergence were compared to districts with no VDPV2 emergence in the same 6-month period using conditional logistic regression. In agreement with the model results, the odds of VDPV2 emergence decreased with higher routine immunisation coverage (odds ratio 0.67 for a 10% absolute increase in coverage [95% confidence interval 0.55 0.82]). We also found that the probability of a VDPV2 emergence resulting in poliomyelitis in >1 child was significantly higher in districts with low serotype 2 population immunity. Our results support a strategy of focused tOPV SIAs before OPV2 withdrawal in areas at risk of VDPV2 emergence and in sufficient number to raise population immunity above the threshold permitting VDPV2 circulation. A failure to implement this risk-based approach could mean these SIAs actually increase the risk of VDPV2 emergence and spread. PMID- 27384948 TI - The Growth Response of Two Diatom Species to Atmospheric Dust from the Last Glacial Maximum. AB - Relief of iron (Fe) limitation in the surface Southern Ocean has been suggested as one driver of the regular glacial-interglacial cycles in atmospheric carbon dioxide (CO2). The proposed cause is enhanced deposition of Fe-bearing atmospheric dust to the oceans during glacial intervals, with consequent effects on export production and the carbon cycle. However, understanding the role of enhanced atmospheric Fe supply in biogeochemical cycles is limited by knowledge of the fluxes and 'bioavailability' of atmospheric Fe during glacial intervals. Here, we assess the effect of Fe fertilization by dust, dry-extracted from the Last Glacial Maximum portion of the EPICA Dome C Antarctic ice core, on the Antarctic diatom species Eucampia antarctica and Proboscia inermis. Both species showed strong but differing reactions to dust addition. E. antarctica increased cell number (3880 vs. 786 cells mL-1), chlorophyll a (51 vs. 3.9 MUg mL-1) and particulate organic carbon (POC; 1.68 vs. 0.28 MUg mL-1) production in response to dust compared to controls. P. inermis did not increase cell number in response to dust, but chlorophyll a and POC per cell both strongly increased compared to controls (39 vs. 15 and 2.13 vs. 0.95 ng cell-1 respectively). The net result of both responses was a greater production of POC and chlorophyll a, as well as decreased Si:C and Si:N incorporation ratios within cells. However, E, antarctica decreased silicate uptake for the same nitrate and carbon uptake, while P. inermis increased carbon and nitrate uptake for the same silicate uptake. This suggests that nutrient utilization changes in response to Fe addition could be driven by different underlying mechanisms between different diatom species. Enhanced supply of atmospheric dust to the surface ocean during glacial intervals could therefore have driven nutrient-utilization changes which could permit greater carbon fixation for lower silica utilization. Additionally, both species responded more strongly to lower amounts of direct Fe chloride addition than they did to dust, suggesting that not all the Fe released from dust was in a bioavailable form available for uptake by diatoms. PMID- 27384949 TI - Development of X-ray micro-focus computed tomography to image and quantify biofilms in central venous catheter models in vitro. AB - Bacterial infections of central venous catheters (CVCs) cause much morbidity and mortality, and are usually diagnosed by concordant culture of blood and catheter tip. However, studies suggest that culture often fails to detect biofilm bacteria. This study optimizes X-ray micro-focus computed tomography (X-ray uCT) for the quantification and determination of distribution and heterogeneity of biofilms in in vitro CVC model systems.Bacterial culture and scanning electron microscopy (SEM) were used to detect Staphylococcus epidermidis ATCC 35984 biofilms grown on catheters in vitro in both flow and static biofilm models. Alongside this, X-ray uCT techniques were developed in order to detect biofilms inside CVCs. Various contrast agent stains were evaluated using energy-dispersive X-ray spectroscopy (EDS) to further optimize these methods. Catheter material and biofilm were segmented using a semi-automated matlab script and quantified using the Avizo Fire software package. X-ray uCT was capable of distinguishing between the degree of biofilm formation across different segments of a CVC flow model. EDS screening of single- and dual-compound contrast stains identified 10 nm gold and silver nitrate as the optimum contrast agent for X-ray uCT. This optimized method was then demonstrated to be capable of quantifying biofilms in an in vitro static biofilm formation model, with a strong correlation between biofilm detection via SEM and culture. X-ray uCT has good potential as a direct, non invasive, non-destructive technology to image biofilms in CVCs, as well as other in vivo medical components in which biofilms accumulate in concealed areas. PMID- 27384950 TI - Aortic Stenosis, a Left Ventricular Disease: Insights from Advanced Imaging. AB - Aortic stenosis (AS) is the most common primary valve disorder in the elderly with an increasing prevalence. It is increasingly clear that it is also a disease of the left ventricle (LV) rather than purely the aortic valve. The transition from left ventricular hypertrophy to fibrosis results in the eventual adverse effects on systolic and diastolic function. Appropriate selection of patients for aortic valve intervention is crucial, and current guidelines recommend aortic valve replacement in severe AS with symptoms or in asymptomatic patients with left ventricular ejection fraction (LVEF) <50 %. LVEF is not a sensitive marker and there are other parameters used in multimodality imaging techniques, including longitudinal strain, exercise stress echo and cardiac MRI that may assist in detecting subclinical and subtle LV dysfunction. These findings offer potentially better ways to evaluate patients, time surgery, predict recovery and potentially offer targets for specific therapies. This article outlines the pathophysiology behind the LV response to aortic stenosis and the role of advanced multimodality imaging in describing it. PMID- 27384952 TI - Management of women with a hereditary predisposition for breast cancer. AB - Women with a hereditary breast cancer predisposition have three management options: screening, chemoprevention (risk-reducing medication) and risk-reducing surgery. However, no randomized trials have addressed the effect of these strategies in mutation carriers. In the general population, randomized trials failed to demonstrate a benefit for screening in premenopausal women. Moreover, although chemoprevention reduces breast cancer incidence in high-risk populations, this benefit is potentially confined to estrogen receptor-positive tumors. Finally, observational studies suggest that prophylactic mastectomy and even prophylactic salpingo-ophorectomy reduces breast cancer risk in BRCA mutation carriers, but there are systematic biases associated with such studies. Therefore, women with a hereditary predisposition for breast cancer should be informed of the three risk-reducing strategies, and that their benefits are not fully understood. PMID- 27384951 TI - HVint: A Strategy for Identifying Novel Protein-Protein Interactions in Herpes Simplex Virus Type 1. AB - Human herpesviruses are widespread human pathogens with a remarkable impact on worldwide public health. Despite intense decades of research, the molecular details in many aspects of their function remain to be fully characterized. To unravel the details of how these viruses operate, a thorough understanding of the relationships between the involved components is key. Here, we present HVint, a novel protein-protein intraviral interaction resource for herpes simplex virus type 1 (HSV-1) integrating data from five external sources. To assess each interaction, we used a scoring scheme that takes into consideration aspects such as the type of detection method and the number of lines of evidence. The coverage of the initial interactome was further increased using evolutionary information, by importing interactions reported for other human herpesviruses. These latter interactions constitute, therefore, computational predictions for potential novel interactions in HSV-1. An independent experimental analysis was performed to confirm a subset of our predicted interactions. This subset covers proteins that contribute to nuclear egress and primary envelopment events, including VP26, pUL31, pUL40, and the recently characterized pUL32 and pUL21. Our findings support a coordinated crosstalk between VP26 and proteins such as pUL31, pUS9, and the CSVC complex, contributing to the development of a model describing the nuclear egress and primary envelopment pathways of newly synthesized HSV-1 capsids. The results are also consistent with recent findings on the involvement of pUL32 in capsid maturation and early tegumentation events. Further, they open the door to new hypotheses on virus-specific regulators of pUS9-dependent transport. To make this repository of interactions readily accessible for the scientific community, we also developed a user-friendly and interactive web interface. Our approach demonstrates the power of computational predictions to assist in the design of targeted experiments for the discovery of novel protein protein interactions. PMID- 27384953 TI - Healthcare system-wide implementation of opioid-safety guideline recommendations: the case of urine drug screening and opioid-patient suicide- and overdose-related events in the Veterans Health Administration. AB - This study provides an example of how healthcare system-wide progress in implementation of opioid-therapy guideline recommendations can be longitudinally assessed and then related to subsequent opioid-prescribed patient health and safety outcomes. Using longitudinal linear mixed effects analyses, we determined that in the Department of Veterans Affairs (VA) healthcare system (n = 141 facilities), over the 4-year interval from 2010 to 2013, a key opioid therapy guideline recommendation, urine drug screening (UDS), increased from 29 to 42 %, with an average within-facility increase rate of 4.5 % per year. Higher levels of UDS implementation from 2010 to 2013 were associated with lower risk of suicide and drug overdose events among VA opioid-prescribed patients in 2013, even after adjusting for patients' 2012 demographic characteristics and medical and mental health comorbidities. Findings suggest that VA clinicians and healthcare policymakers have been responsive to the 2010 VA/Department of Defense (DOD) UDS treatment guideline recommendation, resulting in improved patient safety for VA opioid-prescribed patients. PMID- 27384954 TI - Determining Spatial Summation and Its Effect on Contrast Sensitivity across the Central 20 Degrees of Visual Field. AB - PURPOSE: Recent studies propose that the use of target stimuli within or close to complete spatial summation reveal larger threshold elevation in ocular disease. The Humphrey Visual Field Analyzer (HFA) is used to assess visual function yet the spatial summation characteristics are unexplored for the central macular region. We therefore wanted to establish the relationship between contrast sensitivity and stimulus size (spatial summation) within the central 20 degrees visual field using the high sampling density of the 10-2 test grid. METHODS: Thresholds were measured for one eye from 37 normal subjects using the HFA 10-2 test grid with all five Goldmann (G) targets (GI to GV). Subject data were converted to 50-year-old equivalent using published and calculated location specific decade correction factors. Spatial summation curves were fitted for all data at all locations. The size of Ricco's critical area (Ac) within which complete spatial summation operates (k = 1), and the slope of partial summation (k < 1: to characterize partial summation), was established. RESULTS: The 50-year old age normative data were determined for all Goldmann stimulus sizes for the 10 2 HFA test grid and showed a marked change in contrast sensitivity for small test stimuli (e.g. GI) and little change in larger test stimuli (e.g. GV). Both the Ac and k values did not vary with age allowing for the application of the age correction factors. Ac and k values increased with eccentricity with GI remaining within complete spatial summation and GII was close or within complete spatial summation. GIII or larger test sizes were always outside complete spatial summation operating within various levels of partial summation. CONCLUSIONS: The developed normative data now allows comparisons of data sets with high sampling density using the 10-2 grid irrespective of subject age. Test size is important when assessing ocular disease yet only GI or GII stimuli operate close to or within complete spatial summation in the macula. Current visual field testing protocols employ GIII which is always outside complete spatial summation and operates under various values of partial summation: GIII may not be the most suitable test size to assess ocular disease affecting the macula. PMID- 27384955 TI - Sonodegradation of cyanidin-3-glucosylrutinoside: degradation kinetic analysis and its impact on antioxidant capacity in vitro. AB - BACKGROUND: As an alternative preservation method for thermal treatment, ultrasound comprises a novel non-thermal processing technology that can significantly avoid undesirable nutritional changes. However, the recent literature indicates that anthocyanin degradation occurs when ultrasound is applied in juice at high amplitude parameters. Such work has mainly focussed on the effect of ultrasound on stability, the antioxidant capacity of cyanidin-3 glucosylrutinoside (Cy-3-glc-rut) and the correlation between anthocyanin degradation and .OH generation in a simulated system. RESULTS: The spectral intensities of Cy-3-glc-rut at 518 and 282 nm decreased with increasing ultrasound power and treatment time. The degradation of Cy-3-glc-rut was consistent with first-order reaction kinetics (r2 > 0.9000) and there was a good linear correlation between anthocyanin degradation and hydroxyl radical formation induced by ultrasound (r2 = 0.9258). Moreover, a decrease in the antioxidant activity of Cy-3-glc-rut after ultrasound evaluated by the 1,1-diphenyl-2 picrylhydrazyl and ferric reducing antioxidant power methods was observed. CONCLUSION: Overall, the results of the present study show that ultrasound will accelerate the degradation of Cy-3-glc-rut with the growth of power over time. (c) 2016 Society of Chemical Industry. PMID- 27384956 TI - Transition of an Anaerobic Escherichia coli Culture to Aerobiosis: Balancing mRNA and Protein Levels in a Demand-Directed Dynamic Flux Balance Analysis. AB - The facultative anaerobic bacterium Escherichia coli is frequently forced to adapt to changing environmental conditions. One important determinant for metabolism is the availability of oxygen allowing a more efficient metabolism. Especially in large scale bioreactors, the distribution of oxygen is inhomogeneous and individual cells encounter frequent changes. This might contribute to observed yield losses during process upscaling. Short-term gene expression data exist of an anaerobic E. coli batch culture shifting to aerobic conditions. The data reveal temporary upregulation of genes that are less efficient in terms of energy conservation than the genes predicted by conventional flux balance analyses. In this study, we provide evidence for a positive correlation between metabolic fluxes and gene expression. We then hypothesize that the more efficient enzymes are limited by their low expression, restricting flux through their reactions. We define a demand that triggers expression of the demanded enzymes that we explicitly include in our model. With these features we propose a method, demand-directed dynamic flux balance analysis, dddFBA, bringing together elements of several previously published methods. The introduction of additional flux constraints proportional to gene expression provoke a temporary demand for less efficient enzymes, which is in agreement with the transient upregulation of these genes observed in the data. In the proposed approach, the applied objective function of growth rate maximization together with the introduced constraints triggers expression of metabolically less efficient genes. This finding is one possible explanation for the yield losses observed in large scale bacterial cultivations where steady oxygen supply cannot be warranted. PMID- 27384957 TI - Introduction to the Special Issue: Discrepancies in Adolescent-Parent Perceptions of the Family and Adolescent Adjustment. AB - Researchers commonly rely on adolescents' and parents' reports to assess family functioning (e.g., conflict, parental monitoring, parenting practices, relationship quality). Recent work indicates that these reports may vary as to whether they converge or diverge in estimates of family functioning. Further, patterns of converging or diverging reports may yield important information about adolescent adjustment and family functioning. This work is part of a larger literature seeking to understand and interpret multi-informant assessments of psychological phenomena, namely mental health. In fact, recent innovations in conceptualizing, measuring, and analyzing multi-informant mental health assessments might meaningfully inform efforts to understand multi-informant assessments of family functioning. Therefore, in this Special Issue we address three aims. First, we provide a guiding framework for using and interpreting multi-informant assessments of family functioning, informed by recent theoretical work focused on using and interpreting multi-informant mental health assessments. Second, we report research on adolescents' and parents' reports of family functioning that leverages the latest methods for measuring and analyzing patterns of convergence and divergence between informants' reports. Third, we report research on measurement invariance and its role in interpreting adolescents' and parents' reports of family functioning. Research and theory reported in this Special Issue have important implications for improving our understanding of the links between multi-informant assessments of family functioning and adolescent adjustment. PMID- 27384958 TI - Expression of Angiotensin II Types 1 and 2 Receptors in Endometriotic Lesions. AB - BACKGROUND/AIM: The aim of this study was to evaluate the gene and protein expression of angiotensin type (AT) 1, AT2 receptors in endometriotic lesions and its relation to prostaglandin (PG) synthases. MATERIALS AND METHODS: Endometriosis samples were obtained from 32 patients with endometriotic cysts. Endometrial tissues were obtained during operations for benign gynecological conditions. The expression of the AT1 and AT2 receptor mRNA and that of PG endoperoxide synthase 2 and microsomal PGE2 synthase-1 (mPGES-1) was examined by quantitative RT-PCR. Immunohistochemical staining was performed for these receptors. RESULTS: AT1 and AT2 receptor proteins were mostly located in endometrial glandular epithelium and some stromal cells. Immunoreactivity of the receptor proteins was observed in both the eutopic endometrium and endometriotic lesions. The AT1/AT2 ratio in endometriotic cysts (median 7.29, range 1.88 187.60) was significantly increased compared with that in the eutopic endometrium in the proliferative-phase in controls (median 1.01, range 0.37-2.09, p < 0.001). There was a relationship between the AT1 mRNA expression and that of mPGES-1 mRNA in the endometriotic cysts (r = 0.394089, p < 0.05). There was a significant relationship between the mRNA expression of the AT2 receptor and that of mPGES-1 in eutopic endometrium of non-endometriotic control (r = 0.610714, p < 0.05). CONCLUSION: Renin-angiotensin system may play an important role in the pathophysiology of endometriosis. PMID- 27384959 TI - Challenge to treat hypertrophic nonunion of the femoral shaft: the Poller screw augmentation technique. AB - The management of a femoral nonunion after intramedullary nailing is challenging. Exchange nailing or plate augmentation has been used to treat hypertrophic nonunions previously. The Poller screw augmentation technique is a simple procedure that can be performed in the outpatient surgery. In this study, we highlight the method of hypertrophic nonunion management according to the specific indication including our Poller screw augmentation technique. PMID- 27384961 TI - Social and Environmental Influences on Physical Activity Levels in Latina Adolescents. AB - OBJECTIVE: To examine social and environmental factors that affect moderate to vigorous physical activity (MVPA) in mid-adolescent Hispanic females. DESIGN AND SAMPLE: Secondary data analysis to examine social and environmental level factors related to MVPA levels in (n = 897) mid-adolescent Hispanic females. MEASURES: Data were retrieved from the National Survey of Children's Health (2011/12). Logistic regression was used to estimate associations for factors with MVPA. RESULTS: Significant mid-adolescent predictors were English speaking, OR 1.64 (95% CI, 1.03-2.61); parental attendance of activities, OR 0.50 (95% CI, 0.31 0.81); peer support, OR 2.74 (95% CI, 1.75-4.29); supportive neighborhood, OR 1.52 (95% CI, 1.03-2.32); and safe school environment, OR 1.67 (95% CI, 1.01 2.74). CONCLUSION: Findings highlight the need for the development of age and culturally appropriate interventions to aid the improvement of participation levels in MVPA among the Latina adolescent population. Additionally, findings suggest recommendations for policy and future research. PMID- 27384960 TI - Tumour sampling method can significantly influence gene expression profiles derived from neoadjuvant window studies. AB - Patient-matched transcriptomic studies using tumour samples before and after treatment allow inter-patient heterogeneity to be controlled, but tend not to include an untreated comparison. Here, Illumina BeadArray technology was used to measure dynamic changes in gene expression from thirty-seven paired diagnostic core and surgically excised breast cancer biopsies obtained from women receiving no treatment prior to surgery, to determine the impact of sampling method and tumour heterogeneity. Despite a lack of treatment and perhaps surprisingly, consistent changes in gene expression were identified during the diagnosis surgery interval (48 up, 2 down; Siggenes FDR 0.05) in a manner independent of both subtype and sampling-interval length. Instead, tumour sampling method was seen to directly impact gene expression, with similar effects additionally identified in six published breast cancer datasets. In contrast with previous findings, our data does not support the concept of a significant wounding or immune response following biopsy in the absence of treatment and instead implicates a hypoxic response following the surgical biopsy. Whilst sampling related gene expression changes are evident in treated samples, they are secondary to those associated with response to treatment. Nonetheless, sampling method remains a potential confounding factor for neoadjuvant study design. PMID- 27384962 TI - Acute-phase proteins as diagnostic markers in horses with colic. AB - OBJECTIVE: To investigate the diagnostic potential of the concentrations of acute phase proteins serum amyloid A (SAA), haptoglobin (Hp), and fibrinogen in blood and peritoneal fluid (PF) for differentiating horses with inflammatory colic (entero-colitis and peritonitis) from those with surgical colic. DESIGN: Prospective observational multicenter study. SETTING: Two university referral hospitals. ANIMALS: Horses referred for severe acute abdominal pain to Hospital 1 (n = 148) or Hospital 2 (n = 78). INTERVENTION: Blood and PF samples collected at admission were used for acute-phase protein concentration measurement. MEASUREMENTS AND MAIN RESULTS: A multivariable logistic model including clinical parameters (lethargy, rectal temperature >38 degrees C [100.4 degrees F], normal rectal examination findings, and gastric reflux of 5-10 L) recorded at admission was constructed from Hospital 1 data. The ability of the model to correctly differentiate inflammatory from surgical colic was 86% determined as area under the receiver operating characteristic curve. Adding blood parameters (WBC, PCV, total plasma protein, lactate, SAA, Hp, and fibrinogen concentrations) to the logistic model based on clinical parameters revealed that only WBC and SAA and fibrinogen concentrations improved the model. With SAA included in the model no additional blood parameters improved the model, and the final model had an area under the curve of 90%. Addition of PF parameters (hemolysis, total protein concentration, WBC, SAA, or Hp concentrations) did not improve the model. When validated in Hospital 2 data, the models had good integrity and diagnostic performance. CONCLUSIONS: Evaluation of SAA in serum improved the ability to differentiate horses with acute inflammatory colic requiring medical treatment from horses with colic requiring surgery, as it allowed an additional 4% of horses to be correctly classified into medical and surgical cases. Improved differentiation of these 2 groups of horses with colic may minimize the risk of unnecessary or delayed surgery. PMID- 27384963 TI - Synthesis and X-ray Characterization of Alkali Metal 2-Acyl-1,1,3,3 tetracyanopropenides. AB - A novel route for synthesis of 2-acyl-1,1,3,3-tetracyanopropenides (ATCN) salts in high yields and excellent purities starting from readily available methyl ketones, malononitrile, bromine, and alkali metal acetates is reported. The starting aryl(heteroaryl) methyl ketones were oxidized to the corresponding alpha ketoaldehydes by new a DMSO-NaBr-H2SO4 oxidation system in yields up to 90% within a short reaction time of 8-10 min. The subsequent stages of ATCN preparation are realized in aqueous media without use of any toxic solvents, in accordance with principle 5 of "green chemistry". Lithium, sodium, potassium, rubidium, and cesium 2-benzoyl-1,1,3,3-tetracyanopropenides were characterized by X-ray diffraction analysis. These salts show a good potential for synthesis of five- and six-membered heterocycles and may serve as potentially useful ligands in coordination and supramolecular chemistry. PMID- 27384964 TI - Shift work parameters and disruption of diurnal cortisol production in female hospital employees. AB - Shift work is associated with an increased risk of cardiovascular diseases (CVD). Disruption of cortisol production is a potential underlying mechanism. This study explored the associations of diurnal quantity and pattern of cortisol production in relation to (1) current shift work status (exclusive day versus rotating days and nights), (2) years of past shift work and (3) parameters of rotating shift work (timing, length and intensity). Female hospital employees (160 day workers and 168 rotating shift workers) from southeastern Ontario, Canada, participated in a cross-sectional study. Participants completed a baseline questionnaire and measures of body height, weight, and waist circumference were taken. Midstream urine samples were collected over two separate 24-hour periods to measure creatinine-adjusted cortisol. Total diurnal cortisol production and pattern were described with two measures of the area under the curve. The effect of shift work on cortisol was modeled using multivariable linear regression analyses. Cortisol production in day workers and shift workers on their day shift were similar; however, shift workers on the night shift had flatter diurnal cortisol curves and produced less cortisol. This suggests that night work is associated with an acute attenuation of cortisol production. PMID- 27384965 TI - Patient Experience Assessment is a Requisite for Quality Evaluation: A Discussion of the In-Center Hemodialysis Consumer Assessment of Health Care Providers and Systems (ICH CAHPS) Survey. PMID- 27384967 TI - Comparative analysis of techniques to prevent laparoscopic fogging. AB - PURPOSE: To evaluate the efficiency and efficacy of two common and commercially available methods to resolve lens fogging: a Fluid Warming System (O.R. Solutions, Chantilly, VA) and the Clearify Visualization System (Covidien, Mansfield, MA). MATERIAL AND METHODS: We prospectively evaluated 40 patients undergoing laparoscopic renal procedures with the Fluid Warming System (first 20 cases) and then the Clearify Visualization System (second 20 cases). We utilized the standard Fluid Warming System per a 30-second modified protocol established in our laboratory. We used the Clearify according to manufacturer instructions. For each procedure we documented the etiology of each episode of visual obstruction, procedure type and surgery duration. We performed a cost analysis. For all cases we used the same insufflator, insufflation trocar location and trocar configuration. RESULTS: All 40 patients completed the study protocol without incident. The mean fogging events per hour for the Fluid Warming System and Clearify Visualization System were 0.7 (0-2.52) and 1.4 (0-5.02), respectively (P = 0.045). Surgery duration and cost per procedure were similar for both systems. CONCLUSION: The Fluid Warming System with modified technique was found to have less fogging events than the Clearify Visualization System, with no difference in operative time or cost. PMID- 27384968 TI - Work-family conflict and time use: psychometric assessment of an instrument in ELSA-Brazil. AB - In this study, we evaluated the psychometric properties of the items to measure the work-family conflict and the time use for personal care and leisure, included in the baseline questionnaire of the Longitudinal Study of Adult Health (ELSA Brazil). We evaluated temporal stability (7-14 days) using kappa statistic and the validity of the construct by the correlation of Kendall's tau with other variables. Test-retest stability was discreet to moderate and the correlations were compatible with the underlying theory. Future studies in the context of ELSA Brazil and in other populations will complement the assessment of its relevance. RESUMO Neste estudo, avaliamos as propriedades psicometricas dos itens para mensurar o conflito trabalho-familia e o uso do tempo para cuidado pessoal e lazer, incluidos no questionario da linha de base do Estudo Longitudinal de Saude do Adulto (ELSA-Brasil). Foram avaliadas a estabilidade temporal (7-14 dias) utilizando estatistica kappa e a validade do construto pela correlacao tau de Kendall com outras variaveis. A estabilidade teste-reteste foi discreta a moderada e as correlacoes, compativeis com a teoria subjacente. Estudos futuros no contexto do ELSA-Brasil e em outras populacoes complementarao a avaliacao da sua pertinencia. PMID- 27384969 TI - Report of the procedure of voluntary interruption of pregnancy at a university hospital in Uruguay. AB - OBJECTIVE: To describe the constitution and operation of a voluntary interruption of pregnancy team of a university hospital, from the outlook of the mental health team. METHODS: In this case study, the following aspects were analyzed: 1) historical background; 2) implementation of Law 18,897 of October 22, 2012; and 3) functioning of the program at the Hospital de Clinicas of the Facultad de Medicina (Universidad de la Republica, Uruguay), taking into account three dimensions: structure, process, and results. RESULTS: Between December 2012 and November 2013, a total of 6,676 voluntary interruptions of pregnancy were reported in Uruguay; out of these, 80 were conducted at the Hospital de Clinicas. The patients' demographic data agreed with those reported at the national level: Of the total patients, 81.0% were aged over 19 years; 6.2% decided to continue with the pregnancy; and only 70.0% attended the subsequent control and received advice on contraception. CONCLUSIONS: In its implementation year in Uruguay, we can assess the experience as positive from the point of view of women's health. Our experience as a mental health team at the Hospital de Clinicas, inserted into the multidisciplinary voluntary interruption of pregnancy team, is in the process of assessment and reformulation of practices. OBJETIVO: Describir la conformacion y funcionamiento de un equipo de interrupcion voluntaria del embarazo de un hospital universitario, desde la mirada del equipo de salud mental. METODOS: En este estudio de caso, se analizan los siguientes aspectos: 1) antecedentes historicos; 2) implementacion de la Ley 18.897 de 22 de octubre de 2012; y 3) funcionamiento del programa en el Hospital de Clinicas de la Facultad de Medicina (Universidad de la Republica, Uruguay), teniendo en cuenta tres dimensiones (estructura, proceso y resultados). RESULTADOS: Entre diciembre de 2012 y noviembre de 2013, se reportaron en Uruguay un total de 6.676 interrupciones voluntarias del embarazo; de ellas, 80 se llevaron a cabo en el Hospital de Clinicas. Los datos sociodemograficos de las pacientes concordaron con los reportados a nivel nacional: 81,0% de las pacientes que consultaron era mayores de 19 anos; 6,2% decidieron continuar con el embarazo; solo 70,0% concurrieron al control posterior y recibieron asesoramiento sobre anticoncepcion. CONCLUSIONES: Al ano de su implementacion, en Uruguay, podemos evaluar la experiencia como positiva desde el punto de vista de la salud de las mujeres. Nuestra experiencia como equipo de salud mental en el Hospital de Clinicas, inserto dentro del equipo multidisciplinario de interrupcion voluntaria del embarazo, se encuentra en pleno proceso de evaluacion y reformulacion de practicas. PMID- 27384970 TI - Aging and health: Self-efficacy for Self-direction in Health Scale. AB - OBJECTIVE: To validate the Escala de Autoeficacia para a Autodirecao na Saude (EAAS - Self-efficacy for Self-direction in Health Scale). METHODS: Non experimental quantitative study of EAAS validation, by confirmatory factorial analyses, evaluating a sample of 508 older adults from the north and the center of Portugal with mean age of 71.67 (from 51 to 96 years), to whom the Self efficacy for Self-direction in Health Scale, the Rosenberg Self-esteem Scale, the Positive and Negative Affect Schedule, the Satisfaction with Life Scale, and the Instrumental Activities of Daily Living Scale were applied. The EAAS was developed from the theoretical constructs of self-efficacy and from self-directed learning within the PALADIN European project framework, aiming to develop an instrument able to assess the extent to which older adults take good care of their health. RESULTS: The internal consistency was 0.87 (Cronbach's alpha) and confirmatory factorial analyses enabled to find a model near the one theoretically proposed, indicating a structure consisting of four dimensions: physical exercise, healthy diet, engaging in health-related learning, and visits to health professionals. From the psychometric point of view, the model in four factors showed quite satisfactory fit indicators. CONCLUSIONS: The Self-efficacy for Self-direction in Health Scale, with 16 items, is adequate to evaluate to what extent older adults have confidence in their ability to take care of their own health, with high degree of autonomy. OBJETIVO: Validar a Escala de Autoeficacia para a Autodirecao no dominio da Saude (EAAS). METODOS: Estudo quantitativo nao experimental de validacao da EAAS, por meio de analises fatoriais confirmatorias, avaliando amostra de 508 seniores e idosos provenientes das regioes Norte e Centro de Portugal com media etaria de 71.67 (51 a 96 anos), a quem foram aplicadas a Escala de Autoeficacia para a Autodirecao na Saude, a Escala de Autoestima de Rosenberg, a Escala de Afeto Positivo e Afeto Negativo, a Escala de Satisfacao Com a Vida e a escala de Atividades Instrumentais da Vida Diaria. A EAAS foi desenvolvida a partir dos construtos teoricos da autoeficacia e da aprendizagem autodirigida no ambito do projeto europeu PALADIN, visando constituir um instrumento apto a avaliar ate que ponto os seniores cuidam bem da sua saude. RESULTADOS: A consistencia interna encontrada foi de 0.87 (alfa de Cronbach) e as analises fatoriais confirmatorias permitiram encontrar um modelo proximo ao proposto teoricamente, indicando uma estrutura constituida por quatro dimensoes: exercicio fisico, alimentacao saudavel, envolvimento em aprendizagens relativas a saude e visitas a profissionais de saude. Do ponto de vista psicometrico, o modelo em quatro fatores mostrou indicadores de ajustamento bastante satisfatorios. CONCLUSOES: A Escala de Autoeficacia para a Autodirecao na Saude, com 16 itens, e adequada para avaliar em que medida os seniores tem confianca na sua capacidade para tomar conta da propria saude, com elevado grau de autonomia. PMID- 27384971 TI - Injury-related hospitalizations in 2002 and 2012 in a Mexican rural hospital: differences between indigenous and non-indigenous inpatients. AB - Data are lacking on the extent and distribution of injuries in rural areas. This study aimed at comparing injury-related hospitalizations between 2002 and 2012 at a rural hospital of northern Mexico focusing on differences between indigenous (IP) and non-indigenous patients (NIP). A retrospective design based on the review of records of patients hospitalized with injury diagnoses was used. Information extracted included ethnicity, sex, age, hospital duration, surgical procedures, complications and discharge outcome. Injury data comprised of main diagnosis, mechanism and body part affected. Patterns were stratified by year and ethnicity. Logistic regression was used to determine the probability of being hospitalized for >1 day. Injury-related mortality increased from 0.4% in 2002 to 3.1% in 2012. The proportion of non-indigenous patients hospitalized also increased by 4.5%. Men accounted for two-thirds of all inpatients. Weapon involvement doubled from 16.6% to 33.6%. Almost half of the patients in 2012 were victims of interpersonal violence. Indigenous patients had a 2.7 higher adjusted odds ratios of being hospitalized for >1 day in 2002 (95% CI 1.2-5.7), though the gap was reduced to 1.9 (1.1-3.5) in 2012. While indigenous patients continue to be more disadvantaged than the non-indigenous, the gaps closed in 2012; the reasons behind these disparities need to be further investigated. PMID- 27384972 TI - Comparison of the wound healing efficacy of polyglycolic acid sheets with fibrin glue and gelatin sponge dressings in a rat cranial periosteal defect model. AB - Oral surgical procedures occasionally require removal of the periosteum due to lesions, and these raw bone surfaces are prone not only to infection but also to scar formation during secondary healing. The objective of this study was to identify successful methods for reconstruction using periosteal defect dressings. We created 1-cm2 defects in the skin and cranial periosteum of 10-week-old male Wistar rats under isoflurane anesthesia. The animals were assigned to three defect treatment groups: (1) polyglycolic acid sheets with fibrin glue dressing (PGA-FG), (2) Spongel(r) gelatin sponge dressing (GS), and (3) open wound (control). Postoperative wound healing was histologically evaluated at 2, 4, and 6 weeks. The moist conditions maintained by the GS and PGA-FG treatments protected the bone surface from the destructive effects of drying and infection. Complete wound healing was observed in the GS group but not for all animals in the PGA-FG and control groups. Histologically, osteoblast proliferation on bone surfaces and complete epithelialization with adnexa were observed in the GS group at 6 weeks after surgery. In contrast, PGA sheets that had not been absorbed inhibited osteoblast proliferation and delayed wound healing in the PGA-FG group. Wound surface dressings maintain a moist environment that promotes wound healing, but PGA materials may not be suitable for cases involving exposed periosteum or bone surfaces due to the observed scar formation and foreign-body reaction. PMID- 27384974 TI - A native promoter and inclusion of an intron is necessary for efficient expression of GFP or mRFP in Armillaria mellea. AB - Armillaria mellea is a significant pathogen that causes Armillaria root disease on numerous hosts in forests, gardens and agricultural environments worldwide. Using a yeast-adapted pCAMBIA0380 Agrobacterium vector, we have constructed a series of vectors for transformation of A. mellea, assembled using yeast-based recombination methods. These have been designed to allow easy exchange of promoters and inclusion of introns. The vectors were first tested by transformation into basidiomycete Clitopilus passeckerianus to ascertain vector functionality then used to transform A. mellea. We show that heterologous promoters from the basidiomycetes Agaricus bisporus and Phanerochaete chrysosporium that were used successfully to control the hygromycin resistance cassette were not able to support expression of mRFP or GFP in A. mellea. The endogenous A. mellea gpd promoter delivered efficient expression, and we show that inclusion of an intron was also required for transgene expression. GFP and mRFP expression was stable in mycelia and fluorescence was visible in transgenic fruiting bodies and GFP was detectable in planta. Use of these vectors has been successful in giving expression of the fluorescent proteins GFP and mRFP in A. mellea, providing an additional molecular tool for this pathogen. PMID- 27384975 TI - A paediatric case of successful non-myeloablative bone marrow transplantation after azacitidine therapy for non-Down syndrome acute megakaryoblastic leukaemia with monosomy 7. AB - We report a patient with non-Down syndrome AML, also known as AMKL, with monosomy 7, who was also obese and had a hearing impairment and mental retardation. Non myeloablative bone marrow transplantation was performed successfully after the patient received less aggressive azacitidine treatment, without the usual intensive induction chemotherapy regimen for AML. PMID- 27384973 TI - Monoethylhexyl Phthalate Elicits an Inflammatory Response in Adipocytes Characterized by Alterations in Lipid and Cytokine Pathways. AB - BACKGROUND: A growing body of evidence links endocrine-disrupting chemicals (EDCs) with obesity-related metabolic diseases. While it has been shown that EDCs can predispose individuals toward adiposity by affecting developmental processes, little is known about the chemicals' effects on adult adipose tissue. OBJECTIVES: Our aim was to study the effects of low, physiologically relevant doses of EDCs on differentiated murine adipocytes. METHODS: We combined metabolomics, proteomics, and gene expression analysis to characterize the effects of mono ethylhexyl phthalate (MEHP) in differentiated adipocytes. RESULTS: Repeated exposure to MEHP over several days led to changes in metabolite and enzyme levels indicating elevated lipogenesis and lipid oxidation. The chemical exposure also increased expression of major inflammatory cytokines, including chemotactic factors. Proteomic and gene expression analysis revealed significant alterations in pathways regulated by peroxisome proliferator activated receptor-gamma (PPARgamma). Inhibiting the nuclear receptor's activity using a chemical antagonist abrogated not only the alterations in PPARgamma-regulated metabolic pathways, but also the increases in cytokine expression. CONCLUSIONS: Our results show that MEHP can induce a pro-inflammatory state in differentiated adipocytes. This effect is at least partially mediated PPARgamma. PMID- 27384976 TI - New approaches and omics tools for mining of vaccine candidates against vector borne diseases. AB - Vector-borne diseases (VBDs) present a major threat to human and animal health, as well as place a substantial burden on livestock production. As a way of sustainable VBD control, focus is set on vaccine development. Advances in genomics and other "omics" over the past two decades have given rise to a "third generation" of vaccines based on technologies such as reverse vaccinology, functional genomics, immunomics, structural vaccinology and the systems biology approach. The application of omics approaches is shortening the time required to develop the vaccines and increasing the probability of discovery of potential vaccine candidates. Herein, we review the development of new generation vaccines for VBDs, and discuss technological advancement and overall challenges in the vaccine development pipeline. Special emphasis is placed on the development of anti-tick vaccines that can quell both vectors and pathogens. PMID- 27384978 TI - Lateral electronic screening in quasi-one-dimensional plasmons. AB - The properties of one-dimensional (1D) plasmons are rather unexplored. We investigated the plasmonic collective excitations, measured as one-dimensional plasmon dispersions with electron energy loss spectroscopy, highly resolved both in energy and lateral momentum, for both phases of Au induced chains on stepped Si(553) substrates. We observe 1D dispersions that are strongly influenced by the lateral chain width and by the interchain coupling. Indications for the existence of two different plasmons originating from two surface bands of the systems are given for the low coverage phase. PMID- 27384977 TI - miR-181a induces sorafenib resistance of hepatocellular carcinoma cells through downregulation of RASSF1 expression. AB - Sorafenib, a multi-kinase inhibitor, is the only standard clinical drug for patients with advanced hepatocellular carcinoma (HCC); however, development of sorafenib resistance in HCC often prevents its long-term efficacy. Therefore, novel targets and strategies are urgently needed to improve the antitumor effect of sorafenib. In the present study, we examined the novel mechanisms of sorafenib resistance of HCC cells by investigating the difference in sorafenib sensitivity between two HCC cell lines. Sorafenib induced more apoptosis of HepG2 cells compared to Hep3B cells. Sorafenib exposure to HepG2 cells but not Hep3B cells increased the expression of proapoptotic factor PUMA, and activated PARP and caspase-3. Notably, microRNA-181a (miR-181a) expression levels were lower in HepG2 cells than in Hep3B cells. Exogenous miR-181a expression in HepG2 cells reduced apoptosis, whereas inhibition of miR-181a in Hpe3B cells increased apoptosis. In addition, we demonstrated that miR-181a directly targets RASSF1, a MAPK signaling factor, and knockdown of RASSF1 increased sorafenib resistance. Taken together, these results suggest that miR-181a provokes sorafenib resistance through suppression of RASSF1. Our data provide important insight into the novel therapeutic strategy against sorafenib resistance of HCC cells by targeting of miR-181a pathway. PMID- 27384981 TI - In Response. PMID- 27384980 TI - A Comparison of Measurements of Change in Respiratory Status in Spontaneously Breathing Volunteers by the ExSpiron Noninvasive Respiratory Volume Monitor Versus the Capnostream Capnometer. AB - BACKGROUND: Current respiratory monitoring technologies such as pulse oximetry and capnography have been insufficient to identify early signs of respiratory compromise in nonintubated patients. Pulse oximetry, when used appropriately, will alert the caregiver to an episode of dangerous hypoxemia. However, desaturation lags significantly behind hypoventilation and alarm fatigue due to false alarms poses an additional problem. Capnography, which measures end-tidal CO2 (EtCO2) and respiratory rate (RR), has not been universally used for nonintubated patients for multiple reasons, including the inability to reliably relate EtCO2 to the level of impending respiratory compromise and lack of patient compliance. Serious complications related to respiratory compromise continue to occur as evidenced by the Anesthesiology 2015 Closed Claims Report. The Anesthesia Patient Safety Foundation has stressed the need to improve monitoring modalities so that "no patient will be harmed by opioid-induced respiratory depression." A recently available, Food and Drug Administration-approved noninvasive respiratory volume monitor (RVM) can continuously and accurately monitor actual ventilation metrics: tidal volume, RR, and minute ventilation (MV). We designed this study to compare the capabilities of capnography versus the RVM to detect changes in respiratory metrics. METHODS: Forty-eight volunteer subjects completed the study. RVM measurements (MV and RR) were collected simultaneously with capnography (EtCO2 and RR) using 2 sampling methods (nasal scoop cannula and snorkel mouthpiece with in-line EtCO2 sensor). For each sampling method, each subject performed 6 breathing trials at 3 different prescribed RRs (slow [5 min], normal [12.6 +/- 0.6 min], and fast [25 min]). All data are presented as mean +/- SEM unless otherwise indicated. RESULTS: Following transitions in prescribed RRs, the RVM reached a new steady state value of MV in 37.7 +/- 1.4 seconds while EtCO2 changes were notably slower, often failing to reach a new asymptote before a 2.5-minute threshold. RRs as measured by RVM and capnography during steady breathing were strongly correlated (R = 0.98 +/- 0.01, bias = Capnograph-based RR - RVM-based RR = 0.21 +/- 1.24 [SD] min). As expected, changes in MV were negatively correlated with changes in EtCO2. However, large changes in MV following transitions in prescribed RR resulted in relatively small changes in EtCO2 (instrument sensitivity = DeltaEtCO2/DeltaMV = -0.71 +/- 0.11 and -0.55 +/- 0.11 mm Hg per 1 L/min for nasal and in-line sampling, respectively). Nasal cannula EtCO2 measurements were on average 4 mm Hg lower than in-line measurements. CONCLUSIONS: RVM measurements of MV change more rapidly and by a greater degree than capnography in response to respiratory changes in nonintubated patients. Earlier detection could enable earlier intervention that could potentially reduce frequency and severity of complications due to respiratory depression. PMID- 27384982 TI - In Response. PMID- 27384983 TI - Mentoring and Role Modeling: The Gifts That Keep On Giving. PMID- 27384986 TI - A novel p-type and metallic dual-functional Cu-Al2O3 ultra-thin layer as the back electrode enabling high performance of thin film solar cells. AB - Increasing the open-circuit voltage (Voc) along with the fill factor (FF) is pivotal for the performance improvement of solar cells. In this work, we report the design and construction of a new structure of CdS/CdTe/Al2O3/Cu using the atomic layer deposition (ALD) method, and then we control Cu diffusion through the Al2O3 atomic layer into the CdTe layer. Surprisingly, this generates a novel p-type and metallic dual-functional Cu-Al2O3 atomic layer. Due to this dual functional character of the Cu-Al2O3 layer, an efficiency improvement of 2% in comparison with the standard cell was observed. This novel dual-functional back contact structure could also be introduced into other thin film solar cells for their efficiency improvement. PMID- 27384985 TI - Quantitative T2 mapping of white matter: applications for ageing and cognitive decline. AB - In MRI, the coherence lifetime T2 is sensitive to the magnetic environment imposed by tissue microstructure and biochemistry in vivo. Here we explore the possibility that the use of T2 relaxometry may provide information complementary to that provided by diffusion tensor imaging (DTI) in ageing of healthy controls (HC), Alzheimer's disease (AD) and mild cognitive impairment (MCI). T2 and diffusion MRI metrics were quantified in HC and patients with MCI and mild AD using multi-echo MRI and DTI. We used tract-based spatial statistics (TBSS) to evaluate quantitative MRI parameters in white matter (WM). A prolonged T2 in WM was associated with AD, and able to distinguish AD from MCI, and AD from HC. Shorter WM T2 was associated with better cognition and younger age in general. In no case was a reduction in T2 associated with poorer cognition. We also applied principal component analysis, showing that WM volume changes independently of T2, MRI diffusion indices and cognitive performance indices. Our data add to the evidence that age-related and AD-related decline in cognition is in part attributable to WM tissue state, and much less to WM quantity. These observations suggest that WM is involved in AD pathology, and that T2 relaxometry is a potential imaging modality for detecting and characterising WM in cognitive decline and dementia. PMID- 27384987 TI - Vdelta2+ and alpha/beta T cells show divergent trajectories during human aging. AB - Chronological aging and a variety of stressors are driving forces towards immunosenescence. While much attention was paid to the main T cell component, alpha/beta T cells, few studies concentrate on the impact of age on gamma/delta T cells' characteristics. The latter are important players of adaptive immunity but also have features associated with innate immunity. Vdelta2+ are the main component of gamma/delta while Vdelta1+ T cells expand upon Cytomegalovirus (CMV) infection and with age. The Vdelta2+ T cells are not influenced by persistent infections but do contribute to immunosurveillance against bacterial pathogens. Here, we focus on Vdelta2+ T cells and report that their composition and functionality is not altered in older adults. We have performed a side-by-side comparison of alpha/beta and Vdelta2 cells by using two robust markers of T cell replicative history and cell differentiation (CD28 and CD27), and cytokine secretion (IFN-gamma and TNF-alpha). Significant differences in Vdelta2 versus alpha/beta homeostasis, as well as phenotypic and functional changes emerged. However, the data strongly suggest a sustained functionality of the Vdelta2 population with age, independently of the challenge. This suggests differential trajectories towards immunosenescence in alpha/beta and Vdelta2+ T cells, most likely explained by their intrinsic functions. PMID- 27384988 TI - Ribosomal protein S3 (rpS3) secreted from various cancer cells is N-linked glycosylated. AB - Ribosomal protein S3 (rpS3) is a 243 amino acid component of the 40S ribosomal small subunit. It has multiple roles in translation and extra-ribosomal functions like apoptosis and DNA repair. RpS3 is secreted only in cancer cell lines. Presently, mass spectrometry analysis revealed rpS3 to be glycosylated at the Asn165 residue. A point mutation at this residue decreased secretion of rpS3 in cancer cell lines. Secretion was also inhibited by the endoplasmic reticulum (ER) Golgi transport inhibitor Brefeldin A and by Tunicamycin, an inhibitor of N linked glycosylation. N-linked glycosylation of rpS3 was confirmed as necessary for rpS3 secretion into culture media via the ER-Golgi dependent pathway. RpS3 bound to Concanavalin A, a carbohydrate binding lectin protein, while treatment with peptide-N-glycosidase F shifted the secreted rpS3 to a lower molecular weight band. In addition, the N165G mutant of rpS3 displayed reduced secretion compared to the wild-type. An in vitro binding assay detected rpS3 homodimer formation via the N-terminal region (rpS3:1-85) and a middle region (rpS3:95 158). The results indicate that the Asn 165 residue of rpS3 is a critical site for N-linked glycosylation and passage through the ER-Golgi secretion pathway. PMID- 27384989 TI - Heterotypic paracrine signaling drives fibroblast senescence and tumor progression of large cell carcinoma of the lung. AB - Senescence in cancer cells acts as a tumor suppressor, whereas in fibroblasts enhances tumor growth. Senescence has been reported in tumor associated fibroblasts (TAFs) from a growing list of cancer subtypes. However, the presence of senescent TAFs in lung cancer remains undefined. We examined senescence in TAFs from primary lung cancer and paired control fibroblasts from unaffected tissue in three major histologic subtypes: adenocarcinoma (ADC), squamous cell carcinoma (SCC) and large cell carcinoma (LCC). Three independent senescence markers (senescence-associated beta-galactosidase, permanent growth arrest and spreading) were consistently observed in cultured LCC-TAFs only, revealing a selective premature senescence. Intriguingly, SCC-TAFs exhibited a poor growth response in the absence of senescence markers, indicating a dysfunctional phenotype rather than senescence. Co-culturing normal fibroblasts with LCC (but not ADC or SCC) cancer cells was sufficient to render fibroblasts senescent through oxidative stress, indicating that senescence in LCC-TAFs is driven by heterotypic signaling. In addition, senescent fibroblasts provided selective growth and invasive advantages to LCC cells in culture compared to normal fibroblasts. Likewise, senescent fibroblasts enhanced tumor growth and lung dissemination of tumor cells when co-injected with LCC cells in nude mice beyond the effects induced by control fibroblasts. These results define the subtype specific aberrant phenotypes of lung TAFs, thereby challenging the common assumption that lung TAFs are a heterogeneous myofibroblast-like cell population regardless of their subtype. Importantly, because LCC often distinguishes itself in the clinic by its aggressive nature, we argue that senescent TAFs may contribute to the selective aggressive behavior of LCC tumors. PMID- 27384990 TI - SIRT1 and LSD1 competitively regulate KU70 functions in DNA repair and mutation acquisition in cancer cells. AB - Acquisition of BCR-ABL mutations underlies drug resistance of chronic myeloid leukemia (CML) to tyrosine kinase inhibitors, but the molecular mechanisms of mutation acquisition are poorly understood. We previously showed that lysine deacetylase sirtuin 1, SIRT1, promotes acquisition of BCR-ABL mutations in association with enhancing KU70 mediated non-homologous end joining DNA repair. In this study, we demonstrate that lysine specific demethylase 1 (LSD1) plays an opposite role to SIRT1 in regulating DNA repair and mutation acquisition. In response to therapeutic stress and DNA damage, LSD1 and SIRT1 compete for binding to KU70 on DNA damage foci globally and on the ABL locus. The recruitment of SIRT1 or LSD1 to KU70 impacts chromatin structure but does not correlate well with their direct histone modification functions, and SIRT1 helps maintain histone H4K16 acetylation and open chromatin for repair. The competitive KU70 binding by these proteins affects cancer cells' ability to repair broken DNA and acquire resistant genetic mutations in CML and prostate cancer cells. We identify that the core domain of KU70 binds both LSD1 and SIRT1, forming a molecular basis for the competition. The C-terminal SAP motif of KU70 mediates LSD1/SIRT1 competitive interaction by suppressing LSD1 binding to KU70 and ectopic expression of SAP-deleted KU70 to CML cells compromises their ability to acquire BCR-ABL mutations. Our study reveals a novel cellular stress response mechanism in cancer cells and a key role of LSD1/SIRT1/KU70 dynamic interaction in regulating DNA repair and mutation acquisition. PMID- 27384991 TI - Associations between CYP1A1 rs1048943 A > G and rs4646903 T > C genetic variations and colorectal cancer risk: Proof from 26 case-control studies. AB - Cytochrome P450 1A1 (CYP1A1) enzyme is one of the most important metabolizing enzymes responsible for the metabolism of numerous xenobiotics. Numerous individual case-control studies have investigated the associations between the CYP1A1 rs1048943 A > G and rs4646903 T > C genetic variations and colorectal cancer (CRC) risk, but the conclusions were controversial. To obtain a scientific conclusion, we performed a meta-analysis based on a total of 26 publications, including 20 studies with 8665 cases and 9953 controls on rs1048943 A > G and 19 studies with 6416 cases and 7551 controls on rs4646903 T > C, respectively. The pooled analysis indicated that rs1048943 A > G was associated with an increased risk of CRC (G vs. A: OR = 1.28, 95% CI = 1.08-1.52; GG vs. AA: OR = 1.54, 95% CI = 1.25-1.91; GA vs. AA: OR = 1.26, 95% CI = 1.00-1.60; GG/GA vs. AA: OR = 1.31, 95% CI = 1.05-1.64; GG vs. GA/AA. OR = 1.56, 95% CI = 1.26-1.91). Stratification analysis showed the association between rs1048943 A > G and CRC risk was more obvious in studies with the population-based (PB) design or high quality score. The association between rs4646903 T > C and CRC risk did not reach statistical significance in the pooled analysis as well as stratification analysis. This meta analysis demonstrated CYP1A1 rs1048943 A > G may increase the susceptibility to CRC instead of rs4646903 T > C. This conclusion suggested CYP1A1 may contribute to the pathogenesis of CRC. PMID- 27384992 TI - Polo-like kinase 1 inhibition diminishes acquired resistance to epidermal growth factor receptor inhibition in non-small cell lung cancer with T790M mutations. AB - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective against non-small cell lung cancer (NSCLC) with activating EGFR mutations, but resistance is inevitable. Mechanisms of acquired resistance include T790M mutations and epithelial-mesenchymal transition (EMT). One potential strategy for overcoming this resistance is the inhibition of polo-like kinase 1 (PLK1) based on our previous studies showing that mesenchymal NSCLC cell lines are more sensitive to PLK1 inhibition than epithelial cell lines. To determine the extent to which PLK1 inhibition overcomes EGFR TKI resistance we measured the effects of the PLK1 inhibitor volasertib alone and in combination with the EGFR inhibitor erlotinib in vitro and in vivo in EGFR mutant NSCLC cell lines with acquired resistance to erlotinib. Two erlotinib-resistant cell lines that underwent EMT had higher sensitivity to volasertib, which caused G2/M arrest and apoptosis, than their parental cells. In all NSCLC cell lines with T790M mutations, volasertib markedly reduced erlotinib resistance. All erlotinib resistant NSCLC cell lines with T790M mutations had higher sensitivity to erlotinib plus volasertib than to erlotinib alone, and the combination treatment caused G2/M arrest and apoptosis. Compared with either agent alone, the combination treatment also caused significantly more DNA damage and greater reductions in tumor size. Our results suggest that PLK1 inhibition is clinically effective against NSCLC that becomes resistant to EGFR inhibition through EMT or the acquisition of a T790M mutation. These results uncover new functions of PLK1 inhibition in the treatment of NSCLC with acquired resistance to EGFR TKIs. PMID- 27384993 TI - Dual tumor suppressing and promoting function of Notch1 signaling in human prostate cancer. AB - Adenocarcinomas of the prostate arise as multifocal heterogeneous lesions as the likely result of genetic and epigenetic alterations and deranged cell-cell communication. Notch signaling is an important form of intercellular communication with a role in growth/differentiation control and tumorigenesis. Contrasting reports exist in the literature on the role of this pathway in prostate cancer (PCa) development. We show here that i) compared to normal prostate tissue, Notch1 expression is significantly reduced in a substantial fraction of human PCas while it is unaffected or even increased in others; ii) acute Notch activation both inhibits and induces process networks associated with prostatic neoplasms; iii) down-modulation of Notch1 expression and activity in immortalized normal prostate epithelial cells increases their proliferation potential, while increased Notch1 activity in PCa cells suppresses growth and tumorigenicity through a Smad3-dependent mechanism involving p21WAF1/CIP1; iv) prostate cancer cells resistant to Notch growth inhibitory effects retain Notch1 induced upregulation of pro-oncogenic genes, like EPAS1 and CXCL6, also overexpressed in human PCas with high Notch1 levels. Taken together, these results reconcile conflicting data on the role of Notch1 in prostate cancer. PMID- 27384995 TI - Dragon (RGMb) induces oxaliplatin resistance in colon cancer cells. AB - Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer mortality. Chemotherapy resistance remains a major challenge for treating advanced CRC. Therefore, the identification of targets that induce drug resistance is a priority for the development of novel agents to overcome resistance. Dragon (also known as RGMb) is a member of the repulsive guidance molecule (RGM) family. We previously showed that Dragon expression increases with CRC progression in human patients. In the present study, we found that Dragon inhibited apoptosis and increased viability of CMT93 and HCT116 cells in the presence of oxaliplatin. Dragon induced resistance of xenograft tumor to oxaliplatinin treatment in mice. Mechanistically, Dragon inhibited oxaliplatin induced JNK and p38 MAPK activation, and caspase-3 and PARP cleavages. Our results indicate that Dragon may be a novel target that induces drug resistance in CRC. PMID- 27384994 TI - Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients. AB - INTRODUCTION: Multiple gene expression based prognostic biomarkers have been repeatedly identified in gastric carcinoma. However, without confirmation in an independent validation study, their clinical utility is limited. Our goal was to establish a robust database enabling the swift validation of previous and future gastric cancer survival biomarker candidates. RESULTS: The entire database incorporates 1,065 gastric carcinoma samples, gene expression data. Out of 29 established markers, higher expression of BECN1 (HR = 0.68, p = 1.5E-05), CASP3 (HR = 0.5, p = 6E-14), COX2 (HR = 0.72, p = 0.0013), CTGF (HR = 0.72, p = 0.00051), CTNNB1 (HR = 0.47, p = 4.3E-15), MET (HR = 0.63, p = 1.3E-05), and SIRT1 (HR = 0.64, p = 2.2E-07) correlated to longer OS. Higher expression of BIRC5 (HR = 1.45, p = 1E-04), CNTN1 (HR = 1.44, p = 3.5E- 05), EGFR (HR = 1.86, p = 8.5E-11), ERCC1 (HR = 1.36, p = 0.0012), HER2 (HR = 1.41, p = 0.00011), MMP2 (HR = 1.78, p = 2.6E-09), PFKB4 (HR = 1.56, p = 3.2E-07), SPHK1 (HR = 1.61, p = 3.1E-06), SP1 (HR = 1.45, p = 1.6E-05), TIMP1 (HR = 1.92, p = 2.2E- 10) and VEGF (HR = 1.53, p = 5.7E-06) were predictive for poor OS. MATERIALS AND METHODS: We integrated samples of three major cancer research centers (Berlin, Bethesda and Melbourne datasets) and publicly available datasets with available follow-up data to form a single integrated database. Subsequently, we performed a literature search for prognostic markers in gastric carcinomas (PubMed, 2012-2015) and re validated their findings predicting first progression (FP) and overall survival (OS) using uni- and multivariate Cox proportional hazards regression analysis. CONCLUSIONS: The major advantage of our analysis is that we evaluated all genes in the same set of patients thereby making direct comparison of the markers feasible. The best performing genes include BIRC5, CASP3, CTNNB1, TIMP-1, MMP-2, SIRT, and VEGF. PMID- 27384996 TI - Prognostic significance and function of the vacuolar H+-ATPase subunit V1E1 in esophageal squamous cell carcinoma. AB - Vacuolar H+-ATPase (V-ATPase), a hetero-multimeric ATP-driven proton pump has recently emerged as a critical regulator of mTOR-induced amino acid sensing for cell growth. Although dysregulated activity of cell growth regulators is often associated with cancer, the prognostic significance and metabolic roles of V ATPase in esophageal cancer progression remain unclear. Here, we show that high levels of V-ATPase subunit V1E1 (V-ATPase V1E1) were significantly associated with shortened disease-free survival in patients with esophageal squamous cell carcinoma (ESCC). Multivariate analysis identified the V-ATPase V1E1 as an independent adverse prognostic factor (hazard ratio;1.748, P = 0.018). In addition, depletion of V-ATPase V1E1 resulted in reduced cell motility, decreased glucose uptake, diminished levels of lactate, and decreased ATP production, as well as inhibition of glycolytic enzyme expression in TE8 esophageal cancer cells. Consistent with these results, the Cancer Genome Atlas (TCGA) data and Gene Set Enrichment Analysis (GSEA) showed a high frequency of copy number alterations of the V-ATPase V1E1 gene, and identified a correlation between levels of V-ATPase V1E1 mRNA and Pyruvate Kinase M2 (PKM2) in ESCC. High expression levels of both V-ATPase V1E1 and phosphorylated PKM2 (p-PKM2), a key player in cancer metabolism, were associated with poorer prognosis in ESCC. Collectively, our findings suggest that expression of the V-ATPase V1E1 has prognostic significance in ESCC, and is closely linked to migration, invasion, and aerobic glycolysis in esophageal cancer cells. PMID- 27384997 TI - Virtual screening, optimization, and identification of a novel specific PTP-MEG2 Inhibitor with potential therapy for T2DM. AB - Megakaryocyte protein tyrosine phosphatase 2 (PTP-MEG2) is a tyrosine phosphatase expressed in megakaryocytic cells, and causes insulin sensitization when down regulated. Therefore, specific inhibitors of PTP-MEG2 are potential candidates for novel Type 2 Diabetes (T2DM)therapy. In this study, we discovered PTP-MEG2 inhibitors using high throughput and virtual screening (HTS/VS) and structural optimization in silicon.Eight compound-candidates were identified from the interactions with PTP-MEG2, protein tyrosine phosphatase 1B (PTP1B) and T cell protein tyrosine phosphatase (TCPTP). Results from enzymatic assays show compounds 4a and 4b inhibited PTP-MEG2 activity with an IC50 of 3.2 MUM and 4.3 MUM, respectively. Further, they showed a 7.5 and 5.5 fold change against PTP1B and TCPTP, respectively. We propose compounds 4a and 4b are PTP-MEG2 inhibitors with potential therapeutic use in T2DM treatment. PMID- 27384998 TI - beta-cell insulin receptor deficiency during in utero development induces an islet compensatory overgrowth response. AB - The presence of insulin receptor (IR) on beta-cells suggests that insulin has an autocrine/paracrine role in the regulation of beta-cell function. It has previously been reported that the beta-cell specific loss of IR (betaIRKO) leads to the development of impaired glycemic regulation and beta-cell death in mice. However, temporally controlled betaIRKO induced during the distinct transitions of fetal pancreas development has yet to be investigated. We hypothesized that the presence of IR on beta-cells during the 2nd transition phase of the fetal murine pancreas is required for maintaining normal islet development.We utilized a mouse insulin 1 promoter driven tamoxifen-inducible Cre-recombinase IR knockout (MIP-betaIRKO) mouse model to investigate the loss of beta-cell IR during pancreatic development at embryonic day (e) 13, a phase of endocrine proliferation and beta-cell fate determination. Fetal pancreata examined at e19 20 showed significantly reduced IR levels in the beta-cells of MIP-betaIRKO mice. Morphologically, MIP-betaIRKO pancreata exhibited significantly enlarged islet size with increased beta-cell area and proliferation. MIP-betaIRKO pancreata also displayed significantly increased Igf-2 protein level and Akt activity with a reduction in phospho-p53 when compared to control littermates. Islet vascular formation and Vegf-a protein level was significantly increased in MIP-betaIRKO pancreata.Our results demonstrate a developmental role for the beta-cell IR, whereby its loss leads to an islet compensatory overgrowth, and contributes further information towards elucidating the temporally sensitive signaling during beta-cell commitment. PMID- 27384999 TI - Lin28B promotes Muller glial cell de-differentiation and proliferation in the regenerative rat retinas. AB - Retinal regeneration and repair are severely impeded in higher mammalian animals. Although Muller cells can be activated and show some characteristics of progenitor cells when injured or under pathological conditions, they quickly form gliosis scars. Unfortunately, the basic mechanisms that impede retinal regeneration remain unknown. We studied retinas from Royal College of Surgeon (RCS) rats and found that let-7 family molecules, let-7e and let-7i, were significantly overexpressed in Muller cells of degenerative retinas. It demonstrated that down-regulation of the RNA binding protein Lin28B was one of the key factors leading to the overexpression of let-7e and let-7i. Lin28B ectopic expression in the Muller cells suppressed overexpression of let-7e and let-7i, stimulated and mobilized Muller glia de-differentiation, proliferation, promoted neuronal commitment, and inhibited glial fate acquisition of de differentiated Muller cells. ERG recordings revealed that the amplitudes of a wave and b-wave were improved significantly after Lin28B was delivered into the subretinal space of RCS rats. In summary, down-regulation of Lin28B as well as up regulation of let-7e and let-7i may be the main factors that impede Muller cell de-differentiation and proliferation in the retina of RCS rats. PMID- 27385001 TI - miR-151-5p, targeting chromatin remodeler SMARCA5, as a marker for the BRCAness phenotype. AB - In recent years, the assessment of biomarkers useful for "precision medicine" has been a hot topic in research. The involvement of microRNAs in the pathogenesis of breast cancer has been highly investigated with the aim of being able to molecularly stratify this highly heterogeneous disease. Our aim was to identify microRNAs targeting DNA repair machinery, through Affymetrix GeneChip miRNA Arrays, in a cohort of BRCA-related and sporadic breast cancers. Moreover, we analyzed microRNA expression taking into account our previous results on the expression of PARP1, because of its importance in targeted therapy. miR-361-5p and miR-151-5p were found to be overexpressed in PARP1-upregulating BRCA-germline mutated and sporadic breast tumors. Pathway enrichment analysis was performed to identify potential target genes to be analyzed in the validation step in an independent cohort. Our results confirmed the overexpression of miR-151-5p and, interestingly, its role in the targeting of SMARCA5, a chromatin remodeler. This result was also confirmed in vitro, both through luciferase assay and by analyzing endogenous levels of SMARCA5 in MCF-7 cell lines using miR-151-5p mimic and inhibitor. In conclusion, our data showed the possibility of considering the overexpression of PARP1 and miR-151-5p as biomarkers useful to correctly treat sporadic breast cancers, which eventually could be considered as BRCAness tumors, with PARP-inhibitors. PMID- 27385000 TI - uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy. AB - There is strong evidence supporting the role of the plasminogen activator system in head and neck squamous cell carcinoma (HNSCC), particularly of its uPA (urokinase plasminogen activator) / uPAR (urokinase plasminogen activator receptor) and SERPINE1 components. Overexpression of uPA/uPAR and SERPINE1 enhances tumor cell migration and invasion and plays a key role in metastasis development, conferring poor prognosis. The apparent paradox of uPA/uPAR and its inhibitor SERPINE1 producing similar effects is solved by the identification of SERPINE1 activated signaling pathways independent of uPA inhibition. Both uPA/uPAR and SERPINE1 are directly linked to the induction of epithelial-to mesenchymal transition, the acquisition of stem cell properties and resistance to antitumor agents. The aim of this review is to provide insight on the deregulation of these proteins in all these processes.We also summarize their potential value as prognostic biomarkers or potential drug targets in HNSCC patients. Concomitant overexpression of uPA/uPAR and SERPINE1 is associated with a higher risk of metastasis and could be used to identify patients that would benefit from an adjuvant treatment. In the future, the specific inhibitors of uPA/uPAR and SERPINE1, which are still under development, could be used to design new therapeutic strategies in HNSCCs. PMID- 27385003 TI - Overexpression of AKR1C3 significantly enhances human prostate cancer cells resistance to radiation. AB - Aldo-keto reductase 1C3(AKR1C3) is an enzyme involved in prostaglandins metabolism. Studies suggest that AKR1C3 has a pivotal role in the radioresistance of esophageal cancer and non-small-cell lung cancer, yet the role of AKR1C3 in prostate cancer cells radiation resistance has not yet been clarified. In our study, we established a stable overexpressing AKR1C3 cell line (AKR1C3-over) derived from the prostate cell line DU145 and its control cell line (Control). We conducted colony formation assay to determine the role of AKR1C3 in radioresistance and we used its chemical inhibitor to detect whether it can restored the sensitivity of the acquired tumor cells. Flow cytometry assay was carried out to detect IR-induced ROS accumulation. Elisa was adopted to dedect the concentration of PGF2alpha in the suspension of the cells after 6GY radiation. Western blotting was used to dedect the MAPK and PPAR gamma. The results demonstrated that overexpression of AKR1C3 in prostate cancer can result in radioresistance and suppression of AKR1C3 via its chemical inhibitor indocin restored the sensitivity of the acquired tumor cells. According to the flow cytometry assay, ROS was decreased by 80% in DU145-over cells. Also overexpression of AKR1C3 could result in the accumulation of prostaglandin F2alpha (PGF2alpha), which can not only promote prostate cancer cell 's proliferation but also could enhance prostate cancer cells resistance to radiation and activated the MAPK pathway and inhibited the expression of PPARgamma. In conclusion, we found that overexpression of AKR1C3 significantly enhanced human prostate cancer cells resistance to radiation through activation of MAPK pathway. PMID- 27385002 TI - Amino acid-dependent signaling via S6K1 and MYC is essential for regulation of rDNA transcription. AB - Dysregulation of RNA polymerase I (Pol I)-dependent ribosomal DNA (rDNA) transcription is a consistent feature of malignant transformation that can be targeted to treat cancer. Understanding how rDNA transcription is coupled to the availability of growth factors and nutrients will provide insight into how ribosome biogenesis is maintained in a tumour environment characterised by limiting nutrients. We demonstrate that modulation of rDNA transcription initiation, elongation and rRNA processing is an immediate, co-regulated response to altered amino acid abundance, dependent on both mTORC1 activation of S6K1 and MYC activity. Growth factors regulate rDNA transcription initiation while amino acids modulate growth factor-dependent rDNA transcription by primarily regulating S6K1-dependent rDNA transcription elongation and processing. Thus, we show for the first time amino acids regulate rRNA synthesis by a distinct, post-initiation mechanism, providing a novel model for integrated control of ribosome biogenesis that has implications for understanding how this process is dysregulated in cancer. PMID- 27385004 TI - mTOR: Alzheimer's disease prevention for APOE4 carriers. PMID- 27385006 TI - Surface and Aggregation Behavior of Pentablock Copolymer PNIPAM7-F127-PNIPAM7 in Aqueous Solutions. AB - The triblock Pluronic F127 was modified by introducing poly(N isopropylacrylamide) (PNIPAM) at both the poly(ethylene oxide) ends, and the pentablock copolymer so-prepared was characterized by gel permeation chromatography and (1)H NMR. The degree of polymerization of NIPAM blocks at the two ends was 7. The solution behavior and microstructure of copolymer aggregates in water and aqueous salt solution were examined and compared with F127 by UV visible absorption spectroscopy, microdifferential scanning calorimetry, dynamic light scattering (DLS), and small-angle neutron scattering (SANS). The behavior of the pentablock copolymer at the air/water interface was determined by Langmuir film balance. Two lower critical solution temperatures were observed for pentablock copolymer, corresponding to poly(propylene oxide) and PNIPAM blocks, respectively. DLS studies show that micelle size increased with increase in temperature and in the presence of salt. SANS measurements provided temperature dependent structural evolution of copolymer micelles in water and salt solution. The copolymer displays an isotherm with four classical regions (pancake, mushroom, brush, and condensed state). The study has potential applications in controlled drug delivery due to the tunable phase behavior and biocompatibility of the copolymer. PMID- 27385005 TI - A meta-analysis of alcohol consumption and thyroid cancer risk. AB - BACKGROUND: It is still inconclusive whether alcohol consumption affects the risk of thyroid cancer. We conducted a meta-analysis of available epidemiological data to address this issue. RESULTS: Compared with nondrinkers, the pooled relative risks (RRs) and corresponding 95% confidential intervals (CIs) of thyroid cancer were 0.80 (95% CI 0.71-0.90) for any drinkers, 0.81 (95% CI 0.70-0.93) for light and 0.71 (95% CI 0.63-0.79) for moderate drinkers. The dose-response analysis suggested that there is no evidence of a dose-risk relationship between alcohol intaking and thyroid cancer risk (P = 0.112). METHODS: Eligible studies were identified by searching PubMed and EMbase databases. A total of 24 studies, included 9,990 cases with thyroid cancer, were included in this meta-analysis. We defined light alcohol intake as <= one drink/day and moderate as >one drink/day. The summary risk estimates were calculated by the random effects model. A dose response analysis was also conducted for modeling the dose-risk relation. CONCLUSION: This meta-analysis confirmed an inverse association between alcohol consumption and thyroid cancer risk. Further studies are needed to better understand the potential mechanisms underlying this association. PMID- 27385007 TI - Socioeconomic inequalities in knee pain, knee osteoarthritis, and health-related quality of life: a population-based cohort study in southern Sweden. AB - OBJECTIVES: To determine socioeconomic inequalities in frequent knee pain (FKP), knee osteoarthritis (OA), and associated health-related quality of life (HRQoL) in Sweden. METHOD: In 2007 a postal questionnaire about knee pain was sent to a random sample of 10 000 residents of Malmo, Sweden (7402 individuals responded). Subjects reporting pain with duration >= 4 weeks in one or both knees in the past 12 months were classified as having FKP. A random sample of 1527 subjects with and without FKP attended a clinical and radiographic knee examination and responded to generic and disease-specific HRQoL questionnaires. We used the individuals' level of education and occupation as socioeconomic status (SES) measures, and we calculated the relative index of inequality (RII) using Poisson regression with robust standard errors adjusted for age and gender. We applied weighting to account for a possible selection bias that might arise from non responses in the study. RESULTS: With education, the RIIs for FKP and knee OA were 0.71 [95% confidence interval (CI) 0.61-0.84] and 0.56 (95% CI 0.34-0.93), respectively. With occupation, the corresponding figures were 0.70 (95% CI 0.60 0.82) and 0.59 (95% CI 0.37-0.94), respectively. There were socioeconomic gradients in HRQoL in favour of people with better SES. RIIs for FKP and HRQoL but not knee OA were essentially similar after additional adjustment for mediators. CONCLUSIONS: In Sweden there are socioeconomic gradients related to both FKP and knee OA as well as HRQoL in favour of people with better SES. SES should be taken into account in health resource allocation pertaining to knee related disorders. PMID- 27385008 TI - JAK/STAT signalling mediates cell survival in response to tissue stress. AB - Tissue homeostasis relies on the ability of tissues to respond to stress. Tissue regeneration and tumour models in Drosophila have shown that c-Jun amino-terminal kinase (JNK) acts as a prominent stress-response pathway promoting injury-induced apoptosis and compensatory proliferation. A central question remaining unanswered is how both responses are balanced by activation of a single pathway. Signalling through the Janus kinase/Signal transducers and activators of transcription (JAK/STAT) pathway, which is a potential JNK target, is implicated in promoting compensatory proliferation. While we observe JAK/STAT activation in imaginal discs upon damage, our data demonstrate that JAK/STAT and its downstream effector Zfh2 promote the survival of JNK signalling cells. The JNK component fos and the pro-apoptotic gene hid are regulated in a JAK/STAT-dependent manner. This molecular pathway restrains JNK-induced apoptosis and spatial propagation of JNK signalling, thereby limiting the extent of tissue damage, as well as facilitating systemic and proliferative responses to injury. We find that the pro-survival function of JAK/STAT also drives tumour growth under conditions of chronic stress. Our study defines the function of JAK/STAT in tissue stress and illustrates how crosstalk between conserved signalling pathways establishes an intricate equilibrium between proliferation, apoptosis and survival to restore tissue homeostasis. PMID- 27385009 TI - Quadruple zebrafish mutant reveals different roles of Mesp genes in somite segmentation between mouse and zebrafish. AB - The segmental pattern of somites is generated by sequential conversion of the temporal periodicity provided by the molecular clock. Whereas the basic structure of this clock is conserved among different species, diversity also exists, especially in terms of the molecular network. The temporal periodicity is subsequently converted into the spatial pattern of somites, and Mesp2 plays crucial roles in this conversion in the mouse. However, it remains unclear whether Mesp genes play similar roles in other vertebrates. In this study, we generated zebrafish mutants lacking all four zebrafish Mesp genes by using TALEN mediated genome editing. Contrary to the situation in the mouse Mesp2 mutant, in the zebrafish Mesp quadruple mutant embryos the positions of somite boundaries were clearly determined and morphological boundaries were formed, although their formation was not completely normal. However, each somite was caudalized in a similar manner to the mouse Mesp2 mutant, and the superficial horizontal myoseptum and lateral line primordia were not properly formed in the quadruple mutants. These results clarify the conserved and species-specific roles of Mesp in the link between the molecular clock and somite morphogenesis. PMID- 27385010 TI - Delineation of proteolytic and non-proteolytic functions of the membrane-anchored serine protease prostasin. AB - The membrane-anchored serine proteases prostasin (PRSS8) and matriptase (ST14) initiate a cell surface proteolytic pathway essential for epithelial function. Mice expressing only catalytically inactive prostasin are viable, unlike prostasin null mice, indicating that at least some prostasin functions are non proteolytic. Here we used knock-in mice expressing catalytically inactive prostasin (Prss8(Ki/Ki)) to show that the physiological and pathological functions of prostasin vary in their dependence on its catalytic activity. Whereas prostasin null mice exhibited partial embryonic and complete perinatal lethality, Prss8(Ki/Ki) mice displayed normal prenatal and postnatal survival. Unexpectedly, catalytically inactive prostasin caused embryonic lethality in mice lacking its cognate inhibitors HAI-1 (SPINT1) or HAI-2 (SPINT2). Proteolytically inactive prostasin, unlike the wild-type protease, was unable to activate matriptase during placentation. Surprisingly, all essential functions of prostasin in embryonic and postnatal development were compensated for by loss of HAI-1, indicating that prostasin is only required for mouse development and overall viability in the presence of this inhibitor. This study expands our knowledge of non-proteolytic functions of membrane-anchored serine proteases and provides unexpected new data on the mechanistic interactions between matriptase and prostasin in the context of epithelial development. PMID- 27385011 TI - Leapfrogging: primordial germ cell transplantation permits recovery of CRISPR/Cas9-induced mutations in essential genes. AB - CRISPR/Cas9 genome editing is revolutionizing genetic loss-of-function analysis but technical limitations remain that slow progress when creating mutant lines. First, in conventional genetic breeding schemes, mosaic founder animals carrying mutant alleles are outcrossed to produce F1 heterozygotes. Phenotypic analysis occurs in the F2 generation following F1 intercrosses. Thus, mutant analyses will require multi-generational studies. Second, when targeting essential genes, efficient mutagenesis of founders is often lethal, preventing the acquisition of mature animals. Reducing mutagenesis levels may improve founder survival, but results in lower, more variable rates of germline transmission. Therefore, an efficient approach to study lethal mutations would be useful. To overcome these shortfalls, we introduce 'leapfrogging', a method combining efficient CRISPR mutagenesis with transplantation of mutated primordial germ cells into a wild type host. Tested using Xenopus tropicalis, we show that founders containing transplants transmit mutant alleles with high efficiency. F1 offspring from intercrosses between F0 animals that carry embryonic lethal alleles recapitulate loss-of-function phenotypes, circumventing an entire generation of breeding. We anticipate that leapfrogging will be transferable to other species. PMID- 27385013 TI - Separate elements of the TERMINAL FLOWER 1 cis-regulatory region integrate pathways to control flowering time and shoot meristem identity. AB - TERMINAL FLOWER 1 (TFL1) is a key regulator of Arabidopsis plant architecture that responds to developmental and environmental signals to control flowering time and the fate of shoot meristems. TFL1 expression is dynamic, being found in all shoot meristems, but not in floral meristems, with the level and distribution changing throughout development. Using a variety of experimental approaches we have analysed the TFL1 promoter to elucidate its functional structure. TFL1 expression is based on distinct cis-regulatory regions, the most important being located 3' of the coding sequence. Our results indicate that TFL1 expression in the shoot apical versus lateral inflorescence meristems is controlled through distinct cis-regulatory elements, suggesting that different signals control expression in these meristem types. Moreover, we identified a cis-regulatory region necessary for TFL1 expression in the vegetative shoot and required for a wild-type flowering time, supporting that TFL1 expression in the vegetative meristem controls flowering time. Our study provides a model for the functional organisation of TFL1 cis-regulatory regions, contributing to our understanding of how developmental pathways are integrated at the genomic level of a key regulator to control plant architecture. PMID- 27385012 TI - Sip1 regulates the generation of the inner nuclear layer retinal cell lineages in mammals. AB - The transcription factor Sip1 (Zeb2) plays multiple roles during CNS development from early acquisition of neural fate to cortical neurogenesis and gliogenesis. In humans, SIP1 (ZEB2) haploinsufficiency leads to Mowat-Wilson syndrome, a complex congenital anomaly including intellectual disability, epilepsy and Hirschsprung disease. Here we uncover the role of Sip1 in retinogenesis. Somatic deletion of Sip1 from mouse retinal progenitors primarily affects the generation of inner nuclear layer cell types, resulting in complete loss of horizontal cells and reduced numbers of amacrine and bipolar cells, while the number of Muller glia is increased. Molecular analysis places Sip1 downstream of the eye field transcription factor Pax6 and upstream of Ptf1a in the gene network required for generating the horizontal and amacrine lineages. Intriguingly, characterization of differentiation dynamics reveals that Sip1 has a role in promoting the timely differentiation of retinal interneurons, assuring generation of the proper number of the diverse neuronal and glial cell subtypes that constitute the functional retina in mammals. PMID- 27385014 TI - Crucial roles of the Arp2/3 complex during mammalian corticogenesis. AB - The polarity and organization of radial glial cells (RGCs), which serve as both stem cells and scaffolds for neuronal migration, are crucial for cortical development. However, the cytoskeletal mechanisms that drive radial glial outgrowth and maintain RGC polarity remain poorly understood. Here, we show that the Arp2/3 complex - the unique actin nucleator that produces branched actin networks - plays essential roles in RGC polarity and morphogenesis. Disruption of the Arp2/3 complex in murine RGCs retards process outgrowth toward the basal surface and impairs apical polarity and adherens junctions. Whereas the former is correlated with an abnormal actin-based leading edge, the latter is consistent with blockage in membrane trafficking. These defects result in altered cell fate, disrupted cortical lamination and abnormal angiogenesis. In addition, we present evidence that the Arp2/3 complex is a cell-autonomous regulator of neuronal migration. Our data suggest that Arp2/3-mediated actin assembly might be particularly important for neuronal cell motility in a soft or poorly adhesive matrix environment. PMID- 27385015 TI - IMP2 axonal localization, RNA interactome, and function in the development of axon trajectories. AB - RNA-based regulatory mechanisms play important roles in the development and plasticity of neural circuits and neurological disease. Developing axons provide a model well suited to the study of RNA-based regulation, and contain specific subsets of mRNAs that are locally translated and have roles in axon pathfinding. However, the RNA-binding proteins involved in axon pathfinding, and their corresponding mRNA targets, are still largely unknown. Here we find that the RNA binding protein IMP2 (Igf2bp2) is strikingly enriched in developing axon tracts, including in spinal commissural axons. We used the HITS-CLIP approach to perform a genome-wide identification of RNAs that interact directly with IMP2 in the native context of developing mouse brain. This IMP2 interactome was highly enriched for mRNA targets related to axon guidance. Accordingly, IMP2 knockdown in the developing spinal cord led to strong defects in commissural axon trajectories at the midline intermediate target. These results reveal a highly distinctive axonal enrichment of IMP2, show that it interacts with a network of axon guidance-related mRNAs, and reveal that it is required for normal axon pathfinding during vertebrate development. PMID- 27385016 TI - The Drosophila neurogenin Tap functionally interacts with the Wnt-PCP pathway to regulate neuronal extension and guidance. AB - The neurogenin (Ngn) transcription factors control early neurogenesis and neurite outgrowth in mammalian cortex. In contrast to their proneural activity, their function in neurite growth is poorly understood. Drosophila has a single predicted Ngn homolog, Tap, of unknown function. Here we show that Tap is not a proneural protein in Drosophila but is required for proper axonal growth and guidance of neurons of the mushroom body, a neuropile required for associative learning and memory. Genetic and expression analyses suggest that Tap inhibits excessive axonal growth by fine regulation of the levels of the Wnt signaling adaptor protein Dishevelled. PMID- 27385017 TI - Myocardin-related transcription factors are required for skeletal muscle development. AB - Myocardin-related transcription factors (MRTFs) play a central role in the regulation of actin expression and cytoskeletal dynamics. Stimuli that promote actin polymerization allow for shuttling of MRTFs to the nucleus where they activate serum response factor (SRF), a regulator of actin and other cytoskeletal protein genes. SRF is an essential regulator of skeletal muscle differentiation and numerous components of the muscle sarcomere, but the potential involvement of MRTFs in skeletal muscle development has not been examined. We explored the role of MRTFs in muscle development in vivo by generating mutant mice harboring a skeletal muscle-specific deletion of MRTF-B and a global deletion of MRTF-A. These double knockout (dKO) mice were able to form sarcomeres during embryogenesis. However, the sarcomeres were abnormally small and disorganized, causing skeletal muscle hypoplasia and perinatal lethality. Transcriptome analysis demonstrated dramatic dysregulation of actin genes in MRTF dKO mice, highlighting the importance of MRTFs in actin cycling and myofibrillogenesis. MRTFs were also shown to be necessary for the survival of skeletal myoblasts and for the efficient formation of intact myotubes. Our findings reveal a central role for MRTFs in sarcomere formation during skeletal muscle development and point to the potential involvement of these transcriptional co-activators in skeletal myopathies. PMID- 27385020 TI - [Quantified self instead of cock fights : The new taxonomy of the social]. AB - The self-measurement boom is linked to many risks despite euphoric assessments and promises of benefit by developers, pioneers and companies. Lifelogging - the sum of all technologies and applications used for digital self-measurement and lifelogs - as a "disruptive" technology is changing our "cultural matrix", the institutionalised rules of coexistence. The measurement of man and the reduction of such to a numerical object and a mere data set are creating a negative principle of organisation of the social. Here, the resulting phenomenon, rational discrimination, is located as a pathology of quantification between statistical and social discrimination, and analysed in its consequences. PMID- 27385019 TI - Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model. AB - We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and function in response to chronic isoproterenol infusion using echocardiography in a panel of 104 inbred mouse strains. We showed that cardiac structure and function, whether under normal or stress conditions, has a strong genetic component, with heritability estimates of left ventricular mass between 61% and 81%. Association analyses of cardiac remodeling traits, corrected for population structure, body size and heart rate, revealed 17 genome-wide significant loci, including several loci containing previously implicated genes. Cardiac tissue gene expression profiling, expression quantitative trait loci, expression-phenotype correlation, and coding sequence variation analyses were performed to prioritize candidate genes and to generate hypotheses for downstream mechanistic studies. Using this approach, we have validated a novel gene, Myh14, as a negative regulator of ISO-induced left ventricular mass hypertrophy in an in vivo mouse model and demonstrated the up-regulation of immediate early gene Myc, fetal gene Nppb, and fibrosis gene Lgals3 in ISO-treated Myh14 deficient hearts compared to controls. PMID- 27385018 TI - Immune reconstitution post allogeneic transplant and the impact of immune recovery on the risk of infection. AB - Infection is the leading cause of non-relapse mortality after allogeneic haematopoietic cell transplantation (HCT). This occurs as a result of dysfunction to the host immune system from the preparative regimen used prior to HCT, combined with a delay in reconstitution of the donor-derived immune system after HCT. In this article, we elaborate on the process of immune reconstitution post HCT that begins with the innate system and is followed by recovery of adaptive immunity. Simultaneously, we describe how the tempo of immune reconstitution influences the risk of various infections. We explain some of the key differences in immune reconstitution and the consequent risk of infections in recipients of peripheral blood stem cell, bone marrow or umbilical cord blood grafts. Other factors that impact on immune recovery are also highlighted. Finally, we allude to various strategies that are being tested to enhance immune reconstitution post HCT. PMID- 27385021 TI - Assessment of atrial fibrillation ablation outcomes with clinic ECG, monthly 24-h Holter ECG, and twice-daily telemonitoring ECG. AB - Differences in the methodologies for evaluating atrial fibrillation (AF) ablation outcomes should be evaluated. In the present study, we compared the AF ablation outcomes among periodic clinic electrocardiography (ECG), 24-h Holter ECG, and telemonitoring ECG to evaluate the differences among these methods. In addition, we evaluated the AF-free survival rate for each method with different durations of the blanking period. A total of 30 AF patients were followed up for 6 months after initial catheter ablation, with clinic ECG on every clinic visit, monthly 24-h Holter ECG, and telemonitoring ECG twice daily and upon symptoms. AF relapse was defined as AF or atrial tachycardia detected with any of the methods. Two patients dropped out of the study, and 28 patients were followed up for 8.8 +/- 2.7 months. Patients underwent 3.6 +/- 0.8 clinic ECG, 5.1 +/- 0.8 Holter ECG, and 273 +/- 68 telemonitoring ECG examinations. During the first, second, third, fourth, fifth, and sixth months of follow-up, Holter ECG detected relapses in 11.1, 8.3, 11.5, 15.4, 4.2, and 4.8 % of patients and telemonitoring ECG detected relapses in 32.1, 25.0, 25.0, 17.9, 28.6, and 17.9 % of patients, respectively. When no duration was set for the blanking period, the AF-free survival rate was significantly lower with telemonitoring ECG (46.4 %) than with Holter ECG (78.6 %, P = 0.013) or clinic ECG (85.7 %, P = 0.002). In addition, when the duration of the blanking period was set to 3 months, the AF-free survival rate was significantly lower with telemonitoring ECG than with clinic ECG (92.9 vs. 71.4 %, P = 0.041). The AF ablation outcomes with twice-daily telemonitoring ECG might differ from those with clinic ECG when the duration of the blanking period is 0-3 months. A follow-up based solely on clinic ECG might underestimate AF recurrence. PMID- 27385023 TI - Interventricular dyssynchrony in a patient with a biventricular physiology and a systemic right ventricle. AB - We describe of a unique pattern of cardiac dyssynchrony in a patient with a biventricular physiology and systemic right ventricle (RV): the interventricular dyssynchrony due to a contraction delay between the left ventricle and RV. In the present case, the cineangiography and intracardiac electrocardiography of the RV did not reveal intraventricular dyssynchrony of the RV, but revealed interventricular dyssynchrony. In addition, the pressure curves of the ventricles exhibited time phase differences between the two ventricles. The cardiac resynchronization therapy determining the pacing lead positions based on the idea of interventricular dyssynchrony induced reverse cardiac remodeling in this patient with systemic RV dysfunction. PMID- 27385022 TI - Administration of tolvaptan with reduction of loop diuretics ameliorates congestion with improving renal dysfunction in patients with congestive heart failure and renal dysfunction. AB - In patients with congestive heart failure and renal dysfunction, high dose of diuretics are necessary to improve congestion, which may progress to renal dysfunction. We examined the efficacy of tolvaptan with reduction of loop diuretics to improve renal function in patients with congestive heart failure and renal dysfunction. We conducted a multicenter, prospective, randomized study in 44 patients with congestive heart failure and renal dysfunction (serum creatinine concentration >=1.1 mg/dl) treated with conventional diuretics. Patients were randomly divided into two groups: tolvaptan (15 mg) with a fixed dose of diuretics or with reducing to a half-dose of diuretics for 7-14 consecutive days. We examined the change of urine volume, body weight, serum creatinine and electrolyte concentrations in each group. Both groups demonstrated significant urine volume increase (724 +/- 176 ml/day in the fixed-dose group and 736 +/- 114 ml/day in the half-dose group) and body weight reduction (1.6 +/- 1.5 kg and 1.6 +/- 1.9 kg, respectively) from baseline, with no differences between the two groups. Serum creatinine concentration was significantly increased in the fixed dose group (from 1.60 +/- 0.47 to 1.74 +/- 0.66 mg/dl, p = 0.03) and decreased in the half-dose group (from 1.98 +/- 0.91 to 1.91 +/- 0.97 mg/dl, p = 0.10). So the mean changes in serum creatinine concentration from baseline significantly differed between the two groups (0.14 +/- 0.08 mg/dl in the fixed-dose group and 0.07 +/- 0.19 mg/dl in the half-dose group, p = 0.006). The administration of tolvaptan with reduction of loop diuretics was clinically effective to ameliorate congestion with improving renal function in patients with congestive heart failure and renal dysfunction. PMID- 27385025 TI - US food subsidies fuel obesity, study finds. PMID- 27385024 TI - Brain natriuretic peptide as a potential novel marker of salt-sensitivity in chronic kidney disease patients without cardiac dysfunction. AB - Although the renin-angiotensin system (RAS) is counter-balanced by a salt sensitive mechanism in the hypertensive state, both are reported to be up regulated in chronic kidney disease (CKD) patients. We conducted this study to evaluate the associations among the RAS, renal function, hypertension, and atherosclerosis, as well as to identify markers for salt-sensitivity. A total of 213 pre-dialysis CKD patients with preserved cardiac function (EF >50 %) were enrolled. Their renal and cardiac biochemical markers and plasma renin activity (PRA) were measured, and echocardiography and carotid artery ultrasound were performed. Their salt intake was estimated by the NaCl excretion from a 24-h collected urine sample. The PRA was higher in patients with hypertension (p = 0.018), and had a significant negative correlation with the eGFR (r = -0.23, p = 0.0067). Importantly, the PRA had a strong negative correlation with the brain natriuretic peptide (BNP) level (r = -0.28, p = 0.017) regardless of whether the patients were being treated with RAS inhibitors. The BNP level was related to the renal functions (eGFR: p = 0.001, ACR: p = 0.009). There was a significant positive correlation between the BNP level and carotid intima-media thickness (p < 0.001). A multivariate analysis revealed that older age and an excess of NaCl excretion were independent predictors of BNP elevation (p = 0.02 and 0.003, respectively). Our analysis revealed details of the counterbalance between BNP and PRA, as well as identifying that excess salt intake is a predictor of BNP elevation. These results indicate that the BNP could be a possible valuable marker for salt sensitivity, and that high salt sensitivity could facilitate atherosclerosis in CKD patients. PMID- 27385026 TI - High potential for weathering and climate effects of non-vascular vegetation in the Late Ordovician. AB - It has been hypothesized that predecessors of today's bryophytes significantly increased global chemical weathering in the Late Ordovician, thus reducing atmospheric CO2 concentration and contributing to climate cooling and an interval of glaciations. Studies that try to quantify the enhancement of weathering by non vascular vegetation, however, are usually limited to small areas and low numbers of species, which hampers extrapolating to the global scale and to past climatic conditions. Here we present a spatially explicit modelling approach to simulate global weathering by non-vascular vegetation in the Late Ordovician. We estimate a potential global weathering flux of 2.8 (km(3) rock) yr(-1), defined here as volume of primary minerals affected by chemical transformation. This is around three times larger than today's global chemical weathering flux. Moreover, we find that simulated weathering is highly sensitive to atmospheric CO2 concentration. This implies a strong negative feedback between weathering by non vascular vegetation and Ordovician climate. PMID- 27385028 TI - The Case Report: A User-Friendly Educational Tool for Psychiatry Residency Programs. PMID- 27385027 TI - Do Customers Flee From HIV? A Survey of HIV Stigma and Its Potential Economic Consequences on Small Businesses in Tshwane (Pretoria), South Africa. AB - HIV stigma and discrimination affect care-seeking behavior and may also affect entrepreneurial activity. We interview 2382 individuals in Pretoria, South Africa, and show that respondents believe that businesses with known HIV+ workers may lose up to half of their customers, although the impact depends on the type of business. Survey respondents' fear of getting HIV from consuming everyday products sold by the business-despite a real infection risk of zero-was a major factor driving perceived decline in customers, especially among food businesses. Respondents' perceptions of the decline in overall life satisfaction when one gets sick from HIV and the respondent's dislike of people with HIV were also important predictors of potential customer exit. We suggest policy mechanisms that could improve the earnings potential of HIV+ workers: reducing public health scare tactics that exacerbate irrational fear of HIV infection risk and enriching public health education about HIV and ARVs to improve perceptions about people with HIV. PMID- 27385029 TI - Outside the Hospital: Lessons Learned from a Community Psychiatry Rotation. PMID- 27385030 TI - Hepatitis C Virus Stimulates Murine CD8alpha-Like Dendritic Cells to Produce Type I Interferon in a TRIF-Dependent Manner. AB - Hepatitis C virus (HCV) induces interferon (IFN) stimulated genes in the liver despite of distinct innate immune evasion mechanisms, suggesting that beyond HCV infected cells other cell types contribute to innate immune activation. Upon coculture with HCV replicating cells, human CD141+ myeloid dendritic cells (DC) produce type III IFN, whereas plasmacytoid dendritic cells (pDC) mount type I IFN responses. Due to limitations in the genetic manipulation of primary human DCs, we explored HCV mediated stimulation of murine DC subsets. Coculture of HCV RNA transfected human or murine hepatoma cells with murine bone marrow-derived DC cultures revealed that only Flt3-L DC cultures, but not GM-CSF DC cultures responded with IFN production. Cells transfected with full length or subgenomic viral RNA stimulated IFN release indicating that infectious virus particle formation is not essential in this process. Use of differentiated DC from mice with genetic lesions in innate immune signalling showed that IFN secretion by HCV stimulated murine DC was independent of MyD88 and CARDIF, but dependent on TRIF and IFNAR signalling. Separating Flt3-L DC cultures into pDC and conventional CD11b-like and CD8alpha-like DC revealed that the CD8alpha-like DC, homologous to the human CD141+ DC, release interferon upon stimulation by HCV replicating cells. In contrast, the other cell types and in particular the pDC did not. Injection of human HCV subgenomic replicon cells into IFN-beta reporter mice confirmed the interferon induction upon HCV replication in vivo. These results indicate that HCV-replicating cells stimulate IFN secretion from murine CD8alpha like DC independent of infectious virus production. Thus, this work defines basic principles of viral recognition by murine DC populations. Moreover, this model should be useful to explore the interaction between dendritic cells during HCV replication and to define how viral signatures are delivered to and recognized by immune cells to trigger IFN release. PMID- 27385032 TI - Blast-phase myeloproliferative neoplasms: risk factors and treatment approaches. AB - INTRODUCTION: The past 10 years have seen dramatic advances in the understanding of the molecular pathogenesis of BCR-ABL negative myeloproliferative neoplasms (MPNs). With this knowledge has come novel, molecularly targeted therapies such as JAK inhibitors that may decrease symptoms and improve quality of life for patients with MPNs. Despite these advances, progression of the disease to an acute leukemic (blast) phase remains difficult to predict and even more difficult to treat, with high rates of disease relapse and mortality. AREAS COVERED: We performed a literature review of known risk factors for progression of MPNs towards blast phase and treatment options for transformed disease, including approved and investigational agents. Herein, we review the current literature and suggest strategies for improving outcomes in the future. Expert commentary: Further understanding of the biologic basis for transformation of MPNs from the chronic to blast phase is needed in order to predict, prevent, and treat these cases. Patients with MPNs in blast phase should be encouraged to participate in clinical trials whenever possible. PMID- 27385031 TI - Coatings of Different Carbon Nanotubes on Platinum Electrodes for Neuronal Devices: Preparation, Cytocompatibility and Interaction with Spiral Ganglion Cells. AB - Cochlear and deep brain implants are prominent examples for neuronal prostheses with clinical relevance. Current research focuses on the improvement of the long term functionality and the size reduction of neural interface electrodes. A promising approach is the application of carbon nanotubes (CNTs), either as pure electrodes but especially as coating material for electrodes. The interaction of CNTs with neuronal cells has shown promising results in various studies, but these appear to depend on the specific type of neurons as well as on the kind of nanotubes. To evaluate a potential application of carbon nanotube coatings for cochlear electrodes, it is necessary to investigate the cytocompatibility of carbon nanotube coatings on platinum for the specific type of neuron in the inner ear, namely spiral ganglion neurons. In this study we have combined the chemical processing of as-delivered CNTs, the fabrication of coatings on platinum, and the characterization of the electrical properties of the coatings as well as a general cytocompatibility testing and the first cell culture investigations of CNTs with spiral ganglion neurons. By applying a modification process to three different as-received CNTs via a reflux treatment with nitric acid, long-term stable aqueous CNT dispersions free of dispersing agents were obtained. These were used to coat platinum substrates by an automated spray-coating process. These coatings enhance the electrical properties of platinum electrodes, decreasing the impedance values and raising the capacitances. Cell culture investigations of the different CNT coatings on platinum with NIH3T3 fibroblasts attest an overall good cytocompatibility of these coatings. For spiral ganglion neurons, this can also be observed but a desired positive effect of the CNTs on the neurons is absent. Furthermore, we found that the well-established DAPI staining assay does not function on the coatings prepared from single-wall nanotubes. PMID- 27385033 TI - The Fecal Microbial Communities of Dairy Cattle Shedding Shiga Toxin-Producing Escherichia coli or Campylobacter jejuni. AB - Cattle are a natural reservoir of Shiga toxin-producing Escherichia coli (STEC) and have recently been recognized as a major source of Campylobacter jejuni contamination. While several factors are known to be associated with bacterial colonization, the underlying microbial factors have not been clarified. In this study, we characterized the fecal microbiota of dairy cattle (n = 24) using next generation sequencing to elucidate the intestinal bacterial communities and the microbial diversity in relation to the presence of the foodborne pathogens STEC and C. jejuni (STEC-positive samples, n = 9; STEC-negative samples, n = 15; C. jejuni-positive samples, n = 9; and C. jejuni-negative samples, n = 15). While no significant differences were observed in alpha diversity between STEC-positive and STEC-negative samples, a high diversity index was observed in C. jejuni positive samples compared to C. jejuni-negative samples. Nine phyla, 13 classes, 18 orders, 47 families, 148 genera, and 261 species were found to be the core microbiota in dairy cattle, covering 80.0-100.0% of the fecal microbial community. Diverse microbial communities were observed between cattle shedding foodborne pathogens and nonshedding cattle. C. jejuni-positive cattle had a higher relative abundance of Bacteroidetes (p = 0.035) and a lower relative abundance of Firmicutes (p = 0.035) compared to C. jejuni-negative cattle. In addition, while the relative abundance of 2 and 6 genera was significantly higher in cattle-shedding STEC and C. jejuni, respectively, the relative abundance of 3 genera was lower in both STEC- and C. jejuni-negative cattle. Our findings provide fundamental information on the bacterial ecology in cattle feces and might be useful in developing strategies to reduce STEC or C. jejuni shedding in dairy cattle, thereby reducing the incidence of STEC infection and campylobacteriosis in humans. PMID- 27385034 TI - Endoscopic-assisted transmastoid decompression of petrous apex cholesterol granuloma. PMID- 27385035 TI - Experimental and theoretical studies on compositions, structures, and IR and NMR spectra of functionalized protic ionic liquids. AB - The compositions and structures of amine-based functionalized protic ionic liquids (PILs), namely N,N-dimethyl(cyanoethyl)ammonium propionate (DMCEAP) and N,N-dimethyl(hydroxyethyl)ammonium propionate (DMEOAP) have been investigated systematically by IR and (1)H NMR spectroscopy and density functional theory (DFT) calculations. Analysis of the IR spectra suggests that both DMCEAP and DMEOAP are composed of neutral and ionized species in the liquid phase, the former one mainly existing in the state of precursor molecules, and the latter mainly as ion-pairs. The ratio of precursor molecules to ion-pairs in the liquid phase depends on the types of precursors, especially the functional groups of cations. (1)H NMR spectra indicate that there is a dynamic equilibrium between the neutral and ionized species, probably due to the formation of some intermediates in the PILs. The DFT calculations have been carried out to reveal the conformation, and obtain the corresponding IR and (1)H NMR spectra of the neutral and ionized species, so that the theoretical support to the experimental results can be provided. The present study will help understand the properties of PILs and provide guidance for further applications of PILs. PMID- 27385036 TI - [Seroprevalence of human parvovirus B19 in children with fever and rash in the North of Tunisia]. AB - The aim of the study is to evaluate the prevalence of specific antibodies anti human parvovirus B19 (PVB19) immunoglobulin M (IgM) and IgG in children with fever and rash. This study involved 257 children aged from 7 months to 15 years with febrile rash unrelated to measles and rubella (seronegative for IgM). The sera were examined by immunoenzymatic assay. Detection of antibodies of PVB19 was done by enzyme-linked immunosorbent assay (Elisa). In our study, prevalence of immunoglobulin G (IgG) and IgM were 44 and 11.3%, respectively. Clinically, children with positive IgM serology had submitted an erythema infectiosum (13/29 cases), myocarditis (1 case), encephalitis (1 case), severe sickle cell anemia (7 cases), and immunocompromised (7 cases). The incidence rate of viral infection was 11.3%; most of the cases of PVB19 infection occurred between the months of May and August. Incidence was higher in the 10-15 years age group (21%). The prevalence of IgG antibody varied and increased with age, it rises from 38.2% in preschool children (19 months-4 years) to 53.5% in those aged between 4.5 and 15 years, reaching 58% in the 10-15 years age group. The four risk factors of PVB19 infection are: (1) those aged between 4.5 and 9 years, which is the most affected age group (P = 0.0018); (2) female gender in children aged between 19 months and 4 years (P = 0.037); (3) transfusion and (4) immune deficiency (P = 0.022 and P = 0.001, respectively). The study of the prevalence of PVB19 infection shows that viral infection is acquired early in childhood, increases with age; viral transmission is favored by the community life. Because of the widespread vaccination program against measles and rubella, the systematic search of PVB19 in front of eruptive fevers becomes important. PMID- 27385037 TI - [Use of dried blood spots in early diagnosis of HIV-1 infection in children born to HIV-infected mothers as part of the prevention of mother-to-child transmission in Benin]. AB - The goal of this study was to evaluate using the molecular diagnosis, infection transmission rate of HIV in children born to HIV-1 positive mothers as part of the prevention of mother-to-child transmission (PMTCT) in Benin. The sample consisted of 524 dried blood spots (DBS) of children born to HIV-1 positive mothers, from 30 sites (PMTCT) taken between October 2009 and June 2010. The diagnosis of HIV-1 was performed by the qualitative detection of viral nucleic acids (RNA and DNA) in DBS on filter paper using the Abbott RealTime((r)) HIV-1 Qualitative assay. We found that 51 DBS were positive (9.7%) and 473 were negative (90.3%). The failure rate of PMTCT among 420 mothers who received antiretroviral prophylaxis was 6.7% (28/420). This failure rate was significantly higher among children born to infected mothers on antiretroviral monotherapy than on triple therapy (HAART). The results of our study enrich the data in the literature on highly active antiretroviral chemoprophylaxis to reduce the transmission of HIV-1 from mother to child. PMID- 27385038 TI - Differentiation/Purification Protocol for Retinal Pigment Epithelium from Mouse Induced Pluripotent Stem Cells as a Research Tool. AB - PURPOSE: To establish a novel protocol for differentiation of retinal pigment epithelium (RPE) with high purity from mouse induced pluripotent stem cells (iPSC). METHODS: Retinal progenitor cells were differentiated from mouse iPSC, and RPE differentiation was then enhanced by activation of the Wnt signaling pathway, inhibition of the fibroblast growth factor signaling pathway, and inhibition of the Rho-associated, coiled-coil containing protein kinase signaling pathway. Expanded pigmented cells were purified by plate adhesion after Accutase(r) treatment. Enriched cells were cultured until they developed a cobblestone appearance with cuboidal shape. The characteristics of iPS-RPE were confirmed by gene expression, immunocytochemistry, and electron microscopy. Functions and immunologic features of the iPS-RPE were also evaluated. RESULTS: We obtained iPS-RPE at high purity (approximately 98%). The iPS-RPE showed apical basal polarity and cellular structure characteristic of RPE. Expression levels of several RPE markers were lower than those of freshly isolated mouse RPE but comparable to those of primary cultured RPE. The iPS-RPE could form tight junctions, phagocytose photoreceptor outer segments, express immune antigens, and suppress lymphocyte proliferation. CONCLUSION: We successfully developed a differentiation/purification protocol to obtain mouse iPS-RPE. The mouse iPS-RPE can serve as an attractive tool for functional and morphological studies of RPE. PMID- 27385040 TI - The relationship between sex change and reproductive success in a protandric marine gastropod. AB - Protandric species switch sex during their lifetime. According to theory, the time (body size) at which sex change occurs is determined by the reproductive success of individuals affected by social interactions as well as by post copulatory factors. Experimental evidence is biased to few social systems making the exploration of general patterns difficult. We used the protandric marine gastropod Crepidula coquimbensis that partakes in intrabrood sibling cannibalism to test the following hypotheses: 1. Male-male competition for access to females and sibling cannibalism determine male reproductive success; 2. Males with greater access to females and with higher reproductive success will have reduced growth rates and will delay sex change. Artificial aggregations with different social structures were constructed and male reproductive success was estimated by paternity analysis. The results supported our expectations showing that male competitive ability for access to the female, time spent by males in the copulatory position, and sibling cannibalism affect reproductive success and influence time to sex change, with less successful males hastening sex change. Also, males that spent more time in the copulatory position had reduced growth rates. Comparing these results with those reported for other sequential hermaphrodites provides evidence supporting general patterns of sex change in nature. PMID- 27385039 TI - Dietary intake of manganese and the risk of the metabolic syndrome in a Chinese population. AB - Animal studies have suggested that Mn might be associated with some components of the metabolic syndrome (MetS). A few epidemiological studies have assessed dietary Mn intake and its association with the risk of the MetS and its components among Chinese adults. In this study, we assessed daily dietary Mn intake and its relationship with MetS risk among Chinese adults in Zhejiang Province using data from the 5th Chinese National Nutrition and Health Survey (2010-2012). A total of 2111 adults were included. Dietary Mn intake was assessed using 3-d 24-h dietary recalls; health-related data were obtained by questionnaire surveys, physical examinations and laboratory assessments. The mean intake of Mn was 6.07 (sd 2.94) mg/d for men (n 998) and 5.13 (sd 2.65) mg/d for women (n 1113). Rice (>42 %) was the main food source of Mn. The prevalence of the MetS was 28.0 % (590/2111). Higher Mn intake was associated with a decreased risk of the MetS in men (Q4 v. Q1 OR 0.62; 95 % CI 0.42, 0.92; P trend=0.043) but an increased risk in women (Q4 v. Q1 OR 1.56; 95 % CI 1.02, 2.45; P trend=0.078). In addition, Mn intake was inversely associated with abdominal obesity (P trend=0.016) and hypertriacylglycerolaemia (P trend=0.029) in men, but positively associated with low HDL-cholesterol in both men (P trend=0.003) and women (P trend<0.001). Our results suggest that higher Mn intakes may be protective against the MetS in men. The inverse association between Mn intake and the MetS in women might be due to the increased risk for low HDL-cholesterol. PMID- 27385041 TI - Breaking down the barriers to international collaboration through technology. PMID- 27385042 TI - Dexmedetomidine and delirium in the ICU. PMID- 27385044 TI - Exploring career anchors among occupational health nurses in Japan: A qualitative study. AB - AIM: This study examined the career anchor characteristics that are possessed by Japanese occupational health nurses. METHOD: Sixteen occupational health nurses participated in the semistructured interview. Data analyses were conducted using descriptive qualitative methods. RESULTS: The data showed the following five categories: practices concerning relationships and positions; development of occupational health practices; management skills for effective work; practices that are approved inside and outside the organization; and work and private life considerations. CONCLUSIONS: This study described the career anchors among occupational health nurses in Japan. The participants emphasized the following: the importance of maintaining good cooperative relationships with workers and supervisors; balancing professional and organized labor; and practicing effective occupational health services. Moreover, the occupational health nurses emphasized receiving approval from inside and outside of the organization. These results were consistent with the actual practices of occupational health nursing. PMID- 27385043 TI - The Effects of Temporal and Spatial Predictions on Stretch Reflexes of Ankle Flexor and Extensor Muscles While Standing. AB - The purpose of the present study was to investigate how stretch reflex (SR) responses in the ankle extensor (soleus: SOL) and flexor (tibialis anterior: TA) muscles would be modulated with temporal and/or spatial predictions of external perturbations and whether their effects are specific to the standing posture. SR responses in the SOL/TA were elicited by imposing quick ankle toes-up/toes-down rotations while standing upright and in the supine position. We designed four experimental conditions based on pre-information about perturbations: no information (No Cue), the timing of the perturbation onset (TIM), the direction of the perturbation (DIR), and both the timing and direction of the perturbation (TIM/DIR). Each condition was separated and its order was counterbalanced. In the SR of TA evoked by toes-down rotation, integrated electromyography activities of the late component were significantly reduced in the TIM and TIM/DIR conditions as compared with those in the No Cue and DIR conditions. The occurrence rate of late SR components that reflects how often the reflex response was observed was also lower in the TIM and TIM/DIR conditions as compared with that in the No Cue and DIR conditions. On the other hand, no significant changes were seen among the four conditions in the early SR component in the TA and both SR components in the SOL. The same results in the occurrence rate were found in the supine position. The present results suggest (1) only temporal predictions have a remarkable effect on the SR excitability of the TA, and (2) this effect is independent of posture. PMID- 27385045 TI - Discovery of a fluorinated 4-oxo-quinoline derivative as a potential positron emission tomography radiotracer for imaging cannabinoid receptor type 2. AB - The cannabinoid receptor type 2 (CB2) is part of the endocannabinoid system and has gained growing attention in recent years because of its important role in neuroinflammatory/neurodegenerative diseases. Recently, we reported on a carbon 11 labeled 4-oxo-quinoline derivative, designated RS-016, as a promising radiotracer for imaging CB2 using PET. In this study, three novel fluorinated analogs of RS-016 were designed, synthesized, and pharmacologically evaluated. The results of our efforts led to the identification of N-(1-adamantyl)-1-(2-(2 fluoroethoxy)ethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxamide (RS-126) as the most potent candidate for evaluation as a CB2 PET ligand. [(18) F]RS-126 was obtained in >= 99% radiochemical purity with an average specific radioactivity of 98 GBq/MUmol at the end of the radiosynthesis. [(18) F]RS-126 showed a logD7.4 value of 1.99 and is stable in vitro in rat and human plasma over 120 min, whereas 55% intact parent compound was found in vivo in rat blood plasma at 10 min post injection. In vitro autoradiographic studies with CB2 positive rat spleen tissue revealed high and blockable binding which was confirmed in in vivo displacement experiments with rats by dynamic PET imaging. Ex vivo biodistribution studies confirmed accumulation of [(18) F]RS-126 in rat spleen with a specificity of 79% under blocking conditions. The moderate elevated CB2 levels in LPS-treated mice brain did not permit the detection of CB2 by [(18) F]RS-126 using PET imaging. In summary, [(18) F]RS-126 demonstrated high specificity toward CB2 receptor in vitro and in vivo and is a promising radioligand for imaging CB2 receptor expression. Cannabinoid receptor type 2 (CB2) is an interesting target for PET imaging. Specific binding of [(18) F]RS 126 in CB2-positive spleen tissue (white arrow head) was confirmed in in vivo displacement experiments with rats. Time activity curve of [(18) F]RS-126 in the spleen after the addition of GW405833 (CB2 specific ligand, green) demonstrates faster radiotracer elimination (blue) compared to the tracer only (red). PMID- 27385046 TI - Traumatic uterine rupture in three felids. AB - OBJECTIVE: To describe 3 near-full-term, young-adult felids (2 domestic shorthair cats, and 1 bobcat [Lynx rufus]) that experienced uterine rupture following trauma. SERIES SUMMARY: Two of the animals had motor vehicular trauma and 1 had abdominal bite wounds. The 2 domestic cats that were treated with surgical exploration and ovariohysterectomy recovered uneventfully. The bobcat died during hospitalization prior to surgical intervention, and necropsy identified uterine rupture and associated peritonitis. UNIQUE INFORMATION PROVIDED: Traumatic uterine rupture should be considered in known or suspected pregnant animals that experience blunt or penetrating trauma, particularly if they are in late-term pregnancy. PMID- 27385049 TI - A Protocol for NMR Analysis of the Enantiomeric Excess of Chiral Diols Using an Achiral Diboronic Acid Template. AB - A practically simple derivatization protocol for determining the enantiopurity of chiral diols by (1)H NMR spectroscopic analysis is described. Diols were treated with 0.5 equiv of 1,3-phenyldiboronic acid to afford mixtures of diastereomeric boronate esters whose homochiral/heterochiral ratios are an accurate reflection of the diol's enantiopurity. PMID- 27385047 TI - Electrochemical Probing through a Redox Capacitor To Acquire Chemical Information on Biothiols. AB - The acquisition of chemical information is a critical need for medical diagnostics, food/environmental monitoring, and national security. Here, we report an electrochemical information processing approach that integrates (i) complex electrical inputs/outputs, (ii) mediators to transduce the electrical I/O into redox signals that can actively probe the chemical environment, and (iii) a redox capacitor that manipulates signals for information extraction. We demonstrate the capabilities of this chemical information processing strategy using biothiols because of the emerging importance of these molecules in medicine and because their distinct chemical properties allow evaluation of hypothesis driven information probing. We show that input sequences can be tailored to probe for chemical information both qualitatively (step inputs probe for thiol-specific signatures) and quantitatively. Specifically, we observed picomolar limits of detection and linear responses to concentrations over 5 orders of magnitude (1 pM 0.1 MUM). This approach allows the capabilities of signal processing to be extended for rapid, robust, and on-site analysis of chemical information. PMID- 27385051 TI - Decreased concentration of serum melatonin in nighttime compared with daytime female medical technologists in South Korea. AB - Working during the night can disrupt the normal circadian rhythm by altering the melatonin level. A low level of melatonin is associated with an increased risk of cancer, possibly by decreasing the expression of tumor-suppressor genes, such as p53. To determine whether nighttime work is associated with melatonin level in serum as well as the expression of related genetic markers, we enrolled 100 female nighttime medical technologists employed at a hospital in South Korea. Melatonin concentration and melatonin receptor 1 (MT1) expression were significantly lower in nighttime than in daytime workers (1.84 pg/mL versus 4.04 pg/mL; 1.16 versus 1.61, respectively). However, p53 expression showed no difference between the groups. In summary, nighttime work could be an important risk factor for circadian disruption, but not a direct risk factor for cancer in medical technologists in South Korea. PMID- 27385050 TI - The effects of cytosine methylation on general transcription factors. AB - DNA methylation on CpG sites is the most common epigenetic modification. Recently, methylation in a non-CpG context was found to occur widely on genomic DNA. Moreover, methylation of non-CpG sites is a highly controlled process, and its level may vary during cellular development. To study non-CpG methylation effects on DNA/protein interactions, we have chosen three human transcription factors (TFs): glucocorticoid receptor (GR), brain and muscle ARNT-like 1 (BMAL1) - circadian locomotor output cycles kaput (CLOCK) and estrogen receptor (ER) with methylated or unmethylated DNA binding sequences, using single-molecule and isothermal titration calorimetry assays. The results demonstrated that these TFs interact with methylated DNA with different effects compared with their cognate DNA sequences. The effects of non-CpG methylation on transcriptional regulation were validated by cell-based luciferase assay at protein level. The mechanisms of non-CpG methylation influencing DNA-protein interactions were investigated by crystallographic analyses and molecular dynamics simulation. With BisChIP-seq assays in HEK-293T cells, we found that GR can recognize highly methylated sites within chromatin in cells. Therefore, we conclude that non-CpG methylation of DNA can provide a mechanism for regulating gene expression through directly affecting the binding of TFs. PMID- 27385052 TI - Engineering de novo disulfide bond in bacterial alpha-type carbonic anhydrase for thermostable carbon sequestration. AB - Exploiting carbonic anhydrase (CA), an enzyme that rapidly catalyzes carbon dioxide hydration, is an attractive biomimetic route for carbon sequestration due to its environmental compatibility and potential economic viability. However, the industrial applications of CA are strongly hampered by the unstable nature of enzymes. In this work, we introduced in silico designed, de novo disulfide bond in a bacterial alpha-type CA to enhance thermostability. Three variants were selected and expressed in Escherichia coli with an additional disulfide bridge. One of the variants showed great enhancement in terms of both kinetic and thermodynamic stabilities. This improvement could be attributed to the loss of conformational entropy of the unfolded state, showing increased rigidity. The variant showed an upward-shifted optimal temperature and appeared to be thermoactivated, which compensated for the lowered activity at 25 degrees C. Collectively, the variant constructed by the rapid and effective de novo disulfide engineering can be used as an efficient biocatalyst for carbon sequestration under high temperature conditions. PMID- 27385053 TI - Comparison of average global exposure of population induced by a macro 3G network in different geographical areas in France and Serbia. AB - This article is the first thorough study of average population exposure to third generation network (3G)-induced electromagnetic fields (EMFs), from both uplink and downlink radio emissions in different countries, geographical areas, and for different wireless device usages. Indeed, previous publications in the framework of exposure to EMFs generally focused on individual exposure coming from either personal devices or base stations. Results, derived from device usage statistics collected in France and Serbia, show a strong heterogeneity of exposure, both in time, that is, the traffic distribution over 24 h was found highly variable, and space, that is, the exposure to 3G networks in France was found to be roughly two times higher than in Serbia. Such heterogeneity is further explained based on real data and network architecture. Among those results, authors show that, contrary to popular belief, exposure to 3G EMFs is dominated by uplink radio emissions, resulting from voice and data traffic, and average population EMF exposure differs from one geographical area to another, as well as from one country to another, due to the different cellular network architectures and variability of mobile usage. Bioelectromagnetics. 37:382-390, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27385055 TI - Improving the quality of life and psychological well-being of recently diagnosed multiple sclerosis patients: preliminary evaluation of a group-based cognitive behavioral intervention. AB - PURPOSE: The study evaluated a group-based cognitive behavioral intervention aimed at promoting the quality of life and the psychological well-being of recently diagnosed multiple sclerosis (MS) patients (up to 3 years since the diagnosis). METHOD: The study involved 85 patients [59% women; mean age 37, SD = 12.3; 94% with relapsing-remitting MS; Expanded Disability Status Scale (EDSS) between 1 and 4]. A quasi-experimental study design was applied; 54 patients (intervention group) participated in five group sessions, a 6-month post intervention and a 1-year follow-up; 31 patients (comparison group) participated in activities routinely provided to recently diagnosed MS patients. Measures of Quality of Life (SF-12), Depression (CESD-10), Affective well-being (PANAS) and Optimism (LOT-R) were assessed. RESULTS: At the 6-month post-intervention, mental health increased in the intervention group and decreased in the comparison group, whereas negative affect decreased in the intervention group and increased in the comparison group. At the 1-year follow-up, mental health and optimism increased in the intervention group and decreased in the comparison group. CONCLUSIONS: Preliminary evidence suggests that the proposed intervention fosters the quality of life and the psychological well-being of recently diagnosed MS patients by reducing negative affect and promoting mental health and optimism, particularly in the long term. Implications for Rehabilitation Preliminary evidence suggests that a group-based cognitive behavioral intervention focused on identity redefinition, sense of coherence and self-efficacy promotes the quality of life (increased mental health) and psychological well-being (decreased negative affect and increased optimism) of recently diagnosed MS patients (up to 3 years since the diagnosis). The first years following the MS diagnosis should be considered a good time for a psychological intervention aimed at promoting the patient's adjustment to the illness. Strategies should be found to increase the participation of recently diagnosed MS patients in psychological interventions. PMID- 27385056 TI - Amorphous Silica: A New Antioxidant Role for Rapid Critical-Sized Bone Defect Healing. AB - Traumatic fractures cause structurally unstable sites due to severe bone loss. Such fractures generate a high yield of reactive oxygen species (ROS) that can lead to oxidative stress. Excessive and prolonged ROS activity impedes osteoblast differentiation and instigates long healing times. Stimulation of antioxidants such as superoxide dismutase (SOD1), are crucial to reduce ROS, stimulate osteogenesis, and strengthen collagen and mineral formation. Yet, no current fixative devices have shown an ability to enhance collagen matrix formation through antioxidant expression. This study reports plasma-enhanced chemical vapor deposition based amorphous silicon oxynitride (Si(ON)x) as a potential new fracture healing biomaterial that adheres well to the implant surface, releases Si(+4) to enhance osteogenesis, and forms a surface hydroxyapatite for collagen mineral attachment. These materials provide a sustained release of Si(+4) in physiological environment for extended times. The dissolution rate partially depends on the film chemistry and can be controlled by varying O/N ratio. The presence of Si(+4) enhances SOD1, which stimulates other osteogenic markers downstream and leads to rapid mineral formation. In vivo testing using a rat critical-sized calvarial defect model shows a more rapid bone-regeneration for these biomaterials as compared to control groups, that implies the clinical significance of the presented biomaterial. PMID- 27385057 TI - Comments on the Systematic Revision of Adeleid Haemogregarines: Are More Data Needed? AB - Haemogregarines are a group of apicomplexan parasites composed of 3 families that infect a wide range of hosts. Many species within these families have been subjected to reclassifications and reassignments, especially because the use of molecular tools to estimate their phylogenetic relationships became more widespread. The 18S rRNA gene has been the only widely used gene for studying the diversity of haemogregarines and recent phylogenetic analyses of this gene have indicated incongruences with the current taxonomy, such that a new genus Bartazoon has recently been proposed. To investigate the current taxonomic situation further, we conducted an overview of all published 18S rRNA sequence data for haemogregarines. We highlight that our understanding of the real diversity and phylogenetic relationships of haemogregarines is still limited, which undermines the proposed systematic revision. Notably all the molecular evidence comes from a single gene, and many studies have shown that single-gene trees often do not reflect species trees. Combined with doubts over the relationships of Hemolivia, the recent identification of a new lineage that could also warrant creation of a new genus, and issues with the type species for Hepatozoon, we suggest that any taxonomic changes now would be premature. In our opinion, type species need to be assessed, sampling across hosts improved, and multiple genes employed prior to taxonomic alterations. Otherwise taxonomic instability will be likely. PMID- 27385054 TI - The role of heparan sulphate in development: the ectodermal story. AB - Heparan sulphate (HS) is ubiquitously expressed and is formed of repeating glucosamine and glucuronic/iduronic acid units which are generally highly sulphated. HS is found in tissues bound to proteins forming HS proteoglycans (HSPGs) which are present on the cell membrane or in the extracellular matrix. HSPGs influence a variety of biological processes by interacting with physiologically important proteins, such as morphogens, creating storage pools, generating morphogen gradients and directly mediating signalling pathways, thereby playing vital roles during development. This review discusses the vital role HS plays in the development of tissues from the ectodermal lineage. The ectodermal layer differentiates to form the nervous system (including the spine, peripheral nerves and brain), eye, epidermis, skin appendages and tooth enamel. PMID- 27385058 TI - Door-to-Needle Time Under 60 Minutes and Picture-to-Puncture Under 90 Minutes: Initiatives and Outcomes in Reducing Time to Recanalization for Cerebral Major Artery Occlusion. AB - The adoption of stent retrievers has significantly improved outcomes of intravenous treatment for acute stroke due to major artery occlusion, and reducing the time to recanalization may achieve further improvements. We reviewed reductions in "door-to-needle time" (DNT) and "picture-to-puncture time" (P2P), as the results of measures to consolidate stroke response capabilities in our hospital, and compared treatment outcomes in acute recanalization patients. We investigated DNT by the route of admission for 96 consecutive patients who received intravenous tissue plasminogen activator between July 2012 and June 2015. We then retrospectively studied 52 patients with acute stroke who underwent endovascular recanalization within 8 h after stroke onset, grouped according to recanalization before (Group I; n = 23) or after (Group II; n = 29) introduction of stent retrievers. Between 2012 and 2015, mean DNT decreased. Significant differences between Groups I and II were only seen in times required, with significantly shorter DNT, picture-to-puncture time, admission to puncture time, and puncture to guiding catheter placement time in Group II. A considerable difference in DNT was seen according to the route of patient admission, and consolidation of hospital stroke response capability successfully reduced the time from admission to recanalization. PMID- 27385059 TI - The Utility of Peripheral Nerve Blocks in Interventional Radiology. AB - OBJECTIVE: The aim of this article is to provide an overview of peripheral nerve blocks, the use of peripheral nerve block within and outside interventional radiology, and the complications of peripheral nerve block. CONCLUSION: Interventional radiologists are often responsible for sedation and pain management in the majority of interventional radiology procedures. Peripheral nerve block is increasingly being used in interventional radiology. PMID- 27385060 TI - Production of dumbbell probe through hairpin cleavage-ligation and increasing RCA sensitivity and specificity by circle to circle amplification. AB - Dumbbell probe (DP) attracts increasing interests in rolling circle amplification (RCA). A universal DP production method through cleavage-ligation of hairpin was proposed and optimized. The production is characterized by restriction endonuclease (RE)-induced cleavage ends ligation. It has the advantage of phosphorylation-free, splint-free and purification-free. To optimize designing, we found that the position of RE cleavage sequence in the stem and the primer position in the loop affected the formation and amplification of DP obviously. Both sticky and blunt ends cleaved by RE produce DP efficiently. Moreover, we introduced this DP into circle to circle (C2C) RCA based on the same cleavage ligation principle, and acquired high sensitivity. By combining a two-ligation design and the C2C strategy, specificity for detecting let-7 family members was increased extremely. Furthermore, coreaction of different steps facilitated convenient formation and amplification process of DP. PMID- 27385062 TI - New Ruthenium Complexes Based on Tetradentate Bipyridine Ligands for Catalytic Hydrogenation of Esters. AB - New bipyridinemethanamine-containing tetradentate ligands and their corresponding ruthenium complexes have been synthesized. The synthesized complexes performed well in the hydrogenation of a variety of esters with high efficiency (TON up to 9700) giving alcohols in good yields. PMID- 27385063 TI - Strategies addressing inadequate information on health factors in pharmacoepidemiology studies relying on healthcare databases: commentary from a public workshop. PMID- 27385061 TI - Persistent effects of chlorine inhalation on respiratory health. AB - Chlorine gas is a toxic respiratory irritant that is considered a chemical threat agent because of the potential for release in industrial accidents or terrorist attacks. Chlorine inhalation damages the respiratory tract, including the airways and distal lung, and can result in acute lung injury. Some individuals exposed to chlorine experience a full recovery from acute injury, whereas others develop persistent adverse effects, such as respiratory symptoms, inflammation, and lung function decrements. In animal models, chlorine can produce persistent inflammation, remodeling, and obstruction in large or small airways, depending on species. Airways with pseudostratified epithelia are repaired efficiently, with surviving basal epithelial cells serving as progenitor cells that repopulate the complement of differentiated cell types. Distal airways lacking basal cells are repaired less efficiently, leading to chronic inflammation and fibrosis at these sites. Persistent chlorine-induced airway disease in humans is treated with asthma medication to relieve symptoms. However, such treatment does not ameliorate the underlying disease pathogenesis, so treatments that are more effective at preventing initial development of airway disease after irritant gas exposure and at reversing established disease are needed. PMID- 27385064 TI - High Electricity Demand in the Northeast U.S.: PJM Reliability Network and Peaking Unit Impacts on Air Quality. AB - On high electricity demand days, when air quality is often poor, regional transmission organizations (RTOs), such as PJM Interconnection, ensure reliability of the grid by employing peak-use electric generating units (EGUs). These "peaking units" are exempt from some federal and state air quality rules. We identify RTO assignment and peaking unit classification for EGUs in the Eastern U.S. and estimate air quality for four emission scenarios with the Community Multiscale Air Quality (CMAQ) model during the July 2006 heat wave. Further, we population-weight ambient values as a surrogate for potential population exposure. Emissions from electricity reliability networks negatively impact air quality in their own region and in neighboring geographic areas. Monitored and controlled PJM peaking units are generally located in economically depressed areas and can contribute up to 87% of hourly maximum PM2.5 mass locally. Potential population exposure to peaking unit PM2.5 mass is highest in the model domain's most populated cities. Average daily temperature and national gross domestic product steer peaking unit heat input. Air quality planning that capitalizes on a priori knowledge of local electricity demand and economics may provide a more holistic approach to protect human health within the context of growing energy needs in a changing world. PMID- 27385066 TI - Proceedings of the American Burn Association 48th Annual Meeting: Erratum. PMID- 27385065 TI - High-throughput analysis of the satellitome illuminates satellite DNA evolution. AB - Satellite DNA (satDNA) is a major component yet the great unknown of eukaryote genomes and clearly underrepresented in genome sequencing projects. Here we show the high-throughput analysis of satellite DNA content in the migratory locust by means of the bioinformatic analysis of Illumina reads with the RepeatExplorer and RepeatMasker programs. This unveiled 62 satDNA families and we propose the term "satellitome" for the whole collection of different satDNA families in a genome. The finding that satDNAs were present in many contigs of the migratory locust draft genome indicates that they show many genomic locations invisible by fluorescent in situ hybridization (FISH). The cytological pattern of five satellites showing common descent (belonging to the SF3 superfamily) suggests that non-clustered satDNAs can become into clustered through local amplification at any of the many genomic loci resulting from previous dissemination of short satDNA arrays. The fact that all kinds of satDNA (micro- mini- and satellites) can show the non-clustered and clustered states suggests that all these elements are mostly similar, except for repeat length. Finally, the presence of VNTRs in bacteria, showing similar properties to non-clustered satDNAs in eukaryotes, suggests that this kind of tandem repeats show common properties in all living beings. PMID- 27385067 TI - Biomonitoring in the Era of the Exposome. AB - BACKGROUND: The term "exposome" was coined in 2005 to underscore the importance of the environment to human health and to bring research efforts in line with those on the human genome. The ability to characterize environmental exposures through biomonitoring is key to exposome research efforts. OBJECTIVES: Our objectives were to describe why traditional and nontraditional (exposomic) biomonitoring are both critical in studies aiming to capture the exposome and to make recommendations on how to transition exposure research toward exposomic approaches. We describe the biomonitoring needs of exposome research and approaches and recommendations that will help fill the gaps in the current science. DISCUSSION: Traditional and exposomic biomonitoring approaches have key advantages and disadvantages for assessing exposure. Exposomic approaches differ from traditional biomonitoring methods in that they can include all exposures of potential health significance, whether from endogenous or exogenous sources. Issues of sample availability and quality, identification of unknown analytes, capture of nonpersistent chemicals, integration of methods, and statistical assessment of increasingly complex data sets remain challenges that must continue to be addressed. CONCLUSIONS: To understand the complexity of exposures faced throughout the lifespan, both traditional and nontraditional biomonitoring methods should be used. Through hybrid approaches and the integration of emerging techniques, biomonitoring strategies can be maximized in research to define the exposome. PMID- 27385068 TI - Evaluation of the toxicity of graphene oxide exposure to the eye. AB - Graphene and its derivatives are the new carbon nanomaterials with the prospect for great applications in electronics, energy storage, biosensors and medicine. However, little is known about the toxicity of graphene or its derivatives in the case of occasional or repeated ocular exposure. We performed in vitro and in vivo studies to evaluate the toxicity of graphene oxide (GO) exposure to the eye. Primary human corneal epithelium cells (hCorECs) and human conjunctiva epithelium cells (hConECs) were exposed to GO (12.5-100 MUg/mL). Acute GO exposure (2 h) did not induce cytotoxicity to hCorECs. However, short-term GO exposure (24 h) exerted significant cytotoxicity to hCorECs and hConECs with increased intracellular reactive oxygen species (ROS). Glutathione (GSH) reduced the GO induced cytotoxicity. We further performed acute eye irritation tests in albino rabbits according to the Organization for Economic Cooperation and Development (OECD) guidelines, and the rabbits did not exhibit corneal opacity, conjunctival redness, abnormality of the iris, or chemosis at any time point after the instillation of 100 MUg/mL of GO. However, 5-day repeated GO exposure (50 and 100 MUg/mL) caused reversible mild corneal opacity, conjunctival redness and corneal epithelium damage to Sprague-Dawley rats, which was also alleviated by GSH. Therefore, our study suggests that GO-induced time- and dose-dependent cytotoxicity to hCorECs and hConECs via oxidative stress. Occasional GO exposure did not cause acute eye irritation; short-term repeated GO exposure generally resulted in reversible damage to the eye via oxidative stress, which may be alleviated by the antioxidant GSH. PMID- 27385069 TI - Electronic origin of the dependence of hydrogen bond strengths on nearest neighbor and next-nearest-neighbor hydrogen bonds in polyhedral water clusters (H2O)n, n = 8, 20 and 24. AB - The influence of the nearest neighbor and next-nearest neighbor water molecules on the strength of the hydrogen (H) bonds was examined for the polyhedral clusters of cubic (H2O)8, dodecahedral (H2O)20 and tetrakaidecahedral (H2O)24 cages. The relative stability and the characteristics of the H bond networks are also studied. The charge-transfer (CT) and dispersion interaction terms of every pair of H bonds are evaluated using perturbation theory based on the locally projected molecular orbitals (LPMO PT). Every water molecule and every H-bonded pair in these polyhedral clusters are classified by the types of the neighbor molecules and H bonds. The relative binding energies among the polyhedral clusters are grouped by these classifications. The optimized OO distances, which are strongly correlated with the calculated pairwise CT terms, are dependent on the 49 sub-groups of the H bonds determined by the type of the neighbor molecules. The electronic origin of this dependence is analyzed using Mulliken's charge-transfer theory, and employing a few assumptions, the analytical formulas for the contribution of the CT terms to the H bond energy are derived. PMID- 27385071 TI - "Reduced" Coumarin Dyes with an O-Phosphorylated 2,2-Dimethyl-4-(hydroxymethyl) 1,2,3,4-tetrahydroquinoline Fragment: Synthesis, Spectra, and STED Microscopy. AB - Large Stokes-shift coumarin dyes with an O-phosphorylated 4-(hydroxymethyl)-2,2 dimethyl-1,2,3,4-tetrahydroquinoline fragment emitting in the blue, green, and red regions of the visible spectrum were synthesized. For this purpose, N substituted and O-protected 1,2-dihydro-7-hydroxy-2,2,4-trimethylquinoline was oxidized with SeO2 to the corresponding alpha,beta-unsaturated aldehyde and then reduced with NaBH4 in a "one-pot" fashion to yield N-substituted and 7-O protected 4-(hydroxymethyl)-7-hydroxy-2,2-dimethyl-1,2,3,4-tetrahydroquinoline as a common precursor to all the coumarin dyes reported here. The photophysical properties of the new dyes ("reduced coumarins") and 1,2-dihydroquinoline analogues (formal precursors) with a trisubstituted C=C bond were compared. The "reduced coumarins" were found to be more photoresistant and brighter than their 1,2-dihydroquinoline counterparts. Free carboxylate analogues, as well as their antibody conjugates (obtained from N-hydroxysuccinimidyl esters) were also prepared. All studied conjugates with secondary antibodies afforded high specificity and were suitable for fluorescence microscopy. The red-emitting coumarin dye bearing a betaine fragment at the C-3-position showed excellent performance in stimulation emission depletion (STED) microscopy. PMID- 27385070 TI - Pertussis vaccination in pregnancy. AB - Pertussis has had a resurgence with the highest incidence and complication rates in young infants, and deaths occurring mainly at < age 3 months. Infants are infected by older individuals whose immunity has waned. Strategies such as targeted immunization of infant caregivers have had limited success. Pertussis vaccination in pregnancy may protect infants through passive and active transfer of maternal antibodies that protect the infant until the primary immunization series. Studies show vaccinating pregnant women with acellular pertussis vaccine is safe for mother and infant, immunogenic with efficient transfer of antibodies to infants, and effective in preventing pertussis in young infants. Vaccine uptake in pregnant women is sub-optimal, but provider recommendation is the most important factor in improving vaccination rates. Studies are ongoing to determine the best timing of vaccination to protect infants, and into other strategies. Vaccinating pregnant women offers hope to prevent pertussis-related morbidity and mortality in infants worldwide. PMID- 27385072 TI - An evolutionary conserved zinc finger protein is involved in Toxoplasma gondii mRNA nuclear export. AB - Apicomplexan parasites are responsible for some of the most deadly parasitic diseases affecting humans and livestock. There is an urgent need for new medicines that will target apicomplexan-specific pathways. We characterized a Toxoplasma gondii C2H2 zinc finger protein, named TgZNF2, which is conserved among eukaryotes. We constructed an inducible KO strain (iKO-TgZNF2) for this gene where the tgznf2 gene expression is repressed in the presence of a tetracycline analog (ATc). We showed that the iKO-TgZNF2 parasites are unable to proliferate after depletion of the TgZNF2 protein. Complementation with a full length copy of the gene restores the phenotype Moreover, the homolog of this protein in the related apicomplexan Plasmodium falciparum was shown to efficiently rescue the phenotype, suggesting that this pathway is likely conserved among apicomplexan parasites. We demonstrated that the iKO-mutant lacking TgZNF2 are arrested during the cell cycle during the G1 phase. We identified potential protein partners of this protein among which are spliceosomal complex and mRNA nuclear export components. We confirmed that TgZNF2 is able to bind in vivo to transcripts but splicing is not perturbed in the ATc treated parasites. Instead, we demonstrated that TgZNF2 depletion leads to the sequestration of polyA+ mRNAs in the nucleus while ribosomal RNAs are not affected. We discovered a conserved protein with specific apicomplexan functional properties that is essential for the survival of T. gondii. TgZNF2 may be crucial to ensure the correct polyA+ mRNA nuclear export, a function that is conserved in P. falciparum. PMID- 27385073 TI - Minimal Basis Iterative Stockholder: Atoms in Molecules for Force-Field Development. AB - Atomic partial charges appear in the Coulomb term of many force-field models and can be derived from electronic structure calculations with a myriad of atoms-in molecules (AIM) methods. More advanced models have also been proposed, using the distributed nature of the electron cloud and atomic multipoles. In this work, an electrostatic force field is defined through a concise approximation of the electron density, for which the Coulomb interaction is trivially evaluated. This approximate "pro-density" is expanded in a minimal basis of atom-centered s-type Slater density functions, whose parameters are optimized by minimizing the Kullback-Leibler divergence of the pro-density from a reference electron density, e.g., obtained from an electronic structure calculation. The proposed method, Minimal Basis Iterative Stockholder (MBIS), is a variant of the Hirshfeld AIM method, but it can also be used as a density-fitting technique. An iterative algorithm to refine the pro-density is easily implemented with a linear-scaling computational cost, enabling applications to supramolecular systems. The benefits of the MBIS method are demonstrated with systematic applications to molecular databases and extended models of condensed phases. A comparison to 14 other AIM methods shows its effectiveness when modeling electrostatic interactions. MBIS is also suitable for rescaling atomic polarizabilities in the Tkatchenko-Scheffler scheme for dispersion interactions. PMID- 27385074 TI - Gaseous and Particulate Content of Laser Hair Removal Plume. AB - Importance: Potentially harmful chemicals are released when tissues are vaporized. Laser hair removal (LHR) causes heating and often vaporization of hairs, producing both a signature malodorous plume and visible particulates. Objective: To characterize the chemical composition and quantify the ultrafine particle content of the plume generated during LHR. Design, Setting, and Participants: In the laser center of a large academic hospital, discarded terminal hairs from the trunk and extremities were collected from 2 adult volunteers. The hair samples were sealed in glass gas chromatography chambers and treated with a laser. The laser plume was analyzed by gas chromatography-mass spectrometry (GC-MS). During LHR treatment, two 6-L negative pressure canisters were used to capture 30 seconds of laser plume, and a portable condensation particle counter was used to measure ultrafine particulates (<1 um). Ultrafine particle concentrations were measured within the treatment room, within the waiting room, and outside the building. Main Outcomes and Measures: The chemical content of the laser plume was analyzed with GC-MS and screened for aerosolized toxins using Environmental Protection Agency-certified methods. The ambient concentration of ultrafine particles during LHR was measured by condensation particle counters. Results: Analysis with GC-MS identified 377 chemical compounds. Sixty-two of these compounds, of which 13 are known or suspected carcinogens and more than 20 are known environmental toxins, exhibited strong absorption peaks. During LHR, the portable condensation particle counters documented an 8-fold increase compared with the ambient room baseline level of ultrafine particle concentrations (ambient room baseline, 15 300 particles per cubic centimeter [ppc]; LHR with smoke evacuator, 129 376 ppc), even when a smoke evacuator was in close proximity (5.0 cm) to the procedure site. When the smoke evacuator was turned off for 30 seconds, there was a more than 26-fold increase in particulate count compared with ambient baseline levels (ambient baseline, 15 300 ppc; LHR without smoke evacuator for 30 seconds, 435 888 ppc). Conclusions and Relevance: These findings establish the concern that the burning-hair plume often present during LHR should be considered a biohazard, warranting the use of smoke evacuators, good ventilation, and respiratory protection, especially for health care workers with prolonged exposure to LHR plume. PMID- 27385075 TI - A Genetically Encoded FRET Sensor for Hypoxia and Prolyl Hydroxylases. AB - Oxygen is vital for all aerobic life forms. Oxygen-dependent hydroxylation of hypoxia-inducible factor (HIF)-1alpha by prolyl hydroxylase domain enzymes (PHDs) is an important step for controlling the expression of oxygen-regulated genes in metazoan species, thereby constituting a molecular mechanism for oxygen sensing and response. Herein, we report a genetically encoded dual-emission ratiometric fluorescent sensor, ProCY, which responds to PHD activities in vitro and in live cells. We demonstrated that ProCY could monitor hypoxia in mammalian cells. By targeting this novel genetically encoded biosensor to the cell nucleus and cytosol, we determined that, under normoxic conditions, the HIF-prolyl hydroxylase activity was mainly confined to the cytosol of HEK 293T cells. The results collectively suggest broad applications of ProCY on the evaluation of hypoxia and PHD activities and understanding of pathways for the control of hypoxic responses. PMID- 27385076 TI - Effects of treatment with etanercept versus methotrexate on sleep quality, fatigue and selected immune parameters in patients with active rheumatoid arthritis. AB - OBJECTIVES: To compare sleep quality, disease activity and patient-reported outcomes such as fatigue and immune parameters in patients with rheumatoid arthritis treated with etanercept (ETA) or methotrexate (MTX). METHODS: Of 36 patients (28-joint Disease Activity Score, DAS28CRP>=3.2) in this 16-week (w), open, prospective study, 19 (11 women) received MTX 12.5-17 mg/w, and 17 (14 women) received ETA 25 mg x 2/w, alone or in combination with MTX. Clinical (DAS28CRP, visual analogue scale), laboratory (C-reactive protein [CRP]), sleep (polysomnography), functional (Multidimensional Fatigue Inventory; Health Assessment Questionnaire-Disability Index (HAQ-DI); 36-item Short-Form Health Survey (SF-36), immunological (humoral/cellular) and neuroendocrine (hormonal) parameters were recorded at baseline (BL), w8 and w16. RESULTS: BL characteristics did not differ significantly between the ETA and MTX groups except disease duration: mean age (years): 48.6+/-8.8 vs. 49.4+/-16.6; mean disease duration (months): 19.6+/-46.3 vs. 81.2+/-79.2; and DAS28CRP: 4.4+/-0.9 vs. 4.4+/-1.7, respectively. DAS28CRP, SF-36, and HAQ-DI improved significantly in both groups from BL to w16 (p<=0.05). The DAS28CRP improvements at w16 (mean changes -1.8 in the ETA group, and -1.4 in MTX group), were not statistically significant from each other. The absolute values of sleep efficiency, total sleep time, and stage 2 sleep duration increased significantly in the ETA group, but no significant changes were reported in the MTX group. CONCLUSIONS: Both therapies improved disease activity, CRP, SF-36 and HAQ-DI, with faster, more pronounced changes in DAS28CRP in the ETA group, which alone had significantly improved sleep parameters. PMID- 27385078 TI - In-gel activity-based protein profiling of a clickable covalent ERK1/2 inhibitor. AB - In-gel activity-based protein profiling (ABPP) offers rapid assessment of the proteome-wide selectivity and target engagement of a chemical tool. Here we demonstrate the use of the inverse electron demand Diels Alder (IEDDA) click reaction for in-gel ABPP by evaluating the selectivity profile and target engagement of a covalent ERK1/2 probe tagged with a trans-cyclooctene group. The chemical probe was shown to bind covalently to Cys166 of ERK2 using protein MS and X-ray crystallography, and displayed submicromolar GI50s in A375 and HCT116 cells. In both cell lines, the probe demonstrated target engagement and a good selectivity profile at low concentrations, which was lost at higher concentrations. The IEDDA cycloaddition enabled fast and quantitative fluorescent tagging for readout with a high background-to-noise ratio and thereby provides a promising alternative to the commonly used copper catalysed alkyne-azide cycloaddition. PMID- 27385079 TI - Gold(III) Mediated Activation and Transformation of Methane on Au1-Doped Vanadium Oxide Cluster Cations AuV2O6(.). AB - Gold in the +III oxidation state (Au(III)) has been proposed as a promising species to mediate challenging chemical reactions. However, it is difficult to characterize the chemistry of individual Au(III) species in condensed-phase systems mainly due to the interference from the Au(I) counterpart. Herein, by doping Au atoms into gas-phase vanadium oxide clusters, we demonstrate that the Au(III) cation in the AuV2O6(+) cluster is active for activation and transformation of methane, the most stable alkane molecule, into formaldehyde under mild conditions. In contrast, the AuV2O6(+) cluster isomers with the Au(I) cation can only absorb CH4. The clusters were generated by laser ablation and mass selected to react with CH4, CD4, or CH2D2 in an ion trap reactor. The reactivity was characterized by mass spectrometry and quantum chemistry calculations. The structures of the reactant and product ions were identified by using collision-induced and 425 nm photo-induced dissociation techniques. PMID- 27385077 TI - Using Electronic Health Record Data to Measure Care Quality for Individuals with Multiple Chronic Medical Conditions. AB - OBJECTIVES: To inform the development of a data-driven measure of quality care for individuals with multiple chronic conditions (MCCs) derived from an electronic health record (EHR). DESIGN: Qualitative study using focus groups, interactive webinars, and a modified Delphi process. SETTING: Research department within an integrated delivery system. PARTICIPANTS: The webinars and Delphi process included 17 experts in clinical geriatrics and primary care, health policy, quality assessment, health technology, and health system operations. The focus group included 10 individuals aged 70-87 with three to six chronic conditions selected from a random sample of individuals aged 65 and older with three or more chronic medical conditions. MEASUREMENTS: Through webinars and the focus group, input was solicited on constructs representing high-quality care for individuals with MCCs. A working list was created of potential measures representing these constructs. Using a modified Delphi process, experts rated the importance of each possible measure and the feasibility of implementing each measure using EHR data. RESULTS: High-priority constructs reflected processes rather than outcomes of care. High-priority constructs that were potentially feasible to measure included assessing physical function, depression screening, medication reconciliation, annual influenza vaccination, outreach after hospital admission, and documented advance directives. High-priority constructs that were less feasible to measure included goal setting and shared decision-making, identifying drug-drug interactions, assessing social support, timely communication with patients, and other aspects of good customer service. Lower priority domains included pain assessment, continuity of care, and overuse of screening or laboratory testing. CONCLUSION: High-quality MCC care should be measured using meaningful process measures rather than outcomes. Although some care processes are currently extractable from electronic data, capturing others will require adapting and applying technology to encourage holistic, person centered care. PMID- 27385080 TI - Detection of Cyclo-N5- in THF Solution. AB - Compelling evidence has been found for the formation and direct detection of the cyclopentazole anion (cyclo-N5- ) in solution. The anion was prepared from phenylpentazole in two steps: reduction by an alkali metal to form the phenylpentazole radical anion, followed by thermal dissociation to yield cyclo-N5 . The reaction solution was analyzed by HPLC coupled with negative mode mass spectrometry. A signal with m/z 70 was eluted about 2.1 min after injection of the sample. Its identification as N5 was supported by single and double labeling with 15 N, which yielded signals at m/z=71 and 72, respectively, with identical retention times in the HPLC column. MS/MS analysis of the m/z=70 signal revealed a dissociation product with m/z=42, which can be assigned to N3- . To our knowledge this is the first preparation of cyclo-N5- in the bulk. The compound is indefinitely stable at temperatures below -40 degrees C, and has a half-life of a few minutes at room temperature. PMID- 27385081 TI - Living donor liver transplantation for biliary atresia - An Indian experience. AB - LT has played a significant role in improving the outcome of children with BA. We review our five-yr experience of LDLT for children with BA. Records of all children who underwent LDLT in our institution over a five-yr period (August 2010 June 2015) were reviewed and those with a primary diagnosis of BA were selected for our study. Data were extracted from a prospectively maintained database. Additional data were collected by review of case notes and imaging studies. Analysis was carried out using standard statistical means. One hundred and thirty two children underwent LDLT at our center over the study period, of which 58 children (31 females) had a primary diagnosis of BA. Thirty-three (56.9%) children had undergone a prior KPE and 25 (43.1%) had a primary LT. Thirty-four children had at least one post-op complication, of which 13 had minor complications (Clavien grades I and II) and 21 had major complications (Clavien grade >II). Thirty-day survival was 96.6% and one-yr survival was 91.4%. Univariate analysis of variables comparing children who did and did not have a KPE prior to LT showed that age at LT, weight at LT, PELD, and GRWR were significantly different. LDLT provides excellent outcomes in children with BA. Primary LDLT and LT after KPE provide equivalent results, although the former is technically more challenging as the child is younger. PMID- 27385082 TI - Triple infection with agamid adenovirus 1, Encephaliton cuniculi-like microsporidium and enteric coccidia in a bearded dragon (Pogona vitticeps). AB - A 2-month-old juvenile central bearded dragon was presented for anorexia and cachexia. Another specimen from the same cage had died suddenly 2 weeks prior. Fecal analysis revealed a high quantity of Isospora amphiboluri and a few pinworm eggs. Other examinations were not performed and the animal died a few days later despite supportive care. A third individual from the same cage presented with anorexia and a distended coelom and was euthanized. In this third dragon, histological examination revealed intestinal coccidiosis, basophilic intranuclear inclusions compatible with adenovirus infection, acute hepatic necrosis with intrahepatocytic and intraenteritic organisms typical of microsporidia and renal gout. A PCR confirmed the diagnosis of adenovirosis. Sequencing showed that the PCR product was 100% identical to the corresponding portion of the agamid adenovirus 1 genome. A PCR for the detection of Encephalitozoon (E.) cuniculi was positive. Partial sequencing revealed 100% identity to an E. cuniculi-like organism previously found in bearded dragons. In cases where environmental factors such as poor hygiene or stress can be excluded, the presence of opportunistic pathogens in high numbers can be due to a systemic (viral) infection with temporary immunosuppression. PMID- 27385083 TI - Investigations of high order plasmonic resonance features of the nano hyper ring. AB - A novel silver hyper ring and its complex nanostructures are designed and its plasmonic properties are investigated numerically. It is found that these hyper ring structures have relative stable optical features. The absorption cross section of the structure changes slightly when the direction and polarization of incident light is adjusting. For the complex structure, the position of each resonance peak does not present obvious change when the relative position of the inner hyper ring and outside larger ring changes. The result of the investigation has great significance for the production of practical nanostructures and the improvement of possible applications. PMID- 27385084 TI - Thymic Stromal Lymphopoietin Promotes Fibrosis and Activates Mitogen-Activated Protein Kinases in MRC-5 Cells. AB - BACKGROUND Acute lung injury (ALI) is a life-threatening hypoxemic respiratory disorder with high incidence and mortality. ALI usually manifests as widespread inflammation and lung fibrosis with the accumulation of pro-inflammatory and pro fibrotic factors and collagen. Thymic stromal lymphopoietin (TSLP) has a significant role in regulation of inflammation but little is known about its roles in lung fibrosis or ALI. This study aimed to define the role and possible regulatory mechanism of TSLP in lung fibrosis. MATERIAL AND METHODS We cultured human lung fibroblast MRC-5 cells and overexpressed or inhibited TSLP by the vector or small interfering RNA transfection. Then, the pro-fibrotic factors skeletal muscle actin alpha (alpha-SMA) and collagen I, and the 4 mitogen activated protein kinases (MAPKs) - MAPK7, p38, extracellular signal-regulated kinase 1 (ERK1), and c-Jun N-terminal kinase 1 (JNK1) - were detected by Western blot. RESULTS Results showed that TSLP promoted the production of alpha-SMA and collagen I (P<0.001), suggesting that it can accelerate MRC-5 cell fibrosis. It also activated the expression of MAPK7, p-p38, p-ERK1, and p-JNK1, but the total MAPK7, p-38, ERK1, and JNK1 protein levels were mostly unchanged, indicating the activated MAPK pathways that might contribute to the promotion of cell fibrosis. CONCLUSIONS This study shows the pro-fibrotic role of TSLP in MRC-5 cells, suggesting TSLP is a potential therapeutic target for treating lung fibrosis in ALI. It possibly functions via activating MAPKs. These findings add to our understanding of the mechanism of fibrosis. PMID- 27385085 TI - Changes in egg quality traits during the last phase of production: is there potential for an extended laying cycle? AB - 1. A field study was conducted to investigate the deterioration of eggshell quality at the end of lay and examine the potential to extend the production cycle. A total of 1200 eggs were assessed originating from commercial farms in Belgium: eggs were random sampled at the collection belt at 57-65 weeks of age and at the end of the production cycle (74-92 weeks). 2. Based on a linear mixed model, egg quality was estimated for an average flock at 60 weeks of age and changes in quality traits were predicted until the end of the laying cycle. 3. Egg weight increased by 0.07 g every week from 60 weeks of age onwards and shape index decreased by 0.04 unit weekly (P < 0.001). Haugh unit values decreased weekly by 0.38 units whereas relative yolk weight was unaffected after 60 weeks of age. Relative albumen weight showed a weekly increase of 0.02% and relative shell decreased by 0.02% weekly until the end of lay. 4. Shell quality traits were also influenced by age: shell index decreased by 0.013 g weekly, shell thickness was calculated to be 0.23 um thinner every week, deformation increased by 0.06 um weekly from 60 weeks to the end of the laying cycle. Variability of the deformation of eggs indicated more heterogeneous shell quality at the end of the production cycle. Dynamic stiffness increased from 60 weeks of age on. 5. Laying hens were depopulated on average at 80 weeks of age (varying from 74-92 weeks). Although ageing had a significant effect on most of the egg quality traits, egg quality was still acceptable at the end of lay, indicating the potential to extend the laying cycle. PMID- 27385086 TI - Direct estimation and correction of bias from temporally variable non-stationary noise in a channelized Hotelling model observer. AB - Channelized Hotelling model observer (CHO) methods were developed to assess performance of an x-ray angiography system. The analytical methods included correction for known bias error due to finite sampling. Detectability indices ([Formula: see text]) corresponding to disk-shaped objects with diameters in the range 0.5-4 mm were calculated. Application of the CHO for variable detector target dose (DTD) in the range 6-240 nGy frame(-1) resulted in [Formula: see text] estimates which were as much as 2.9* greater than expected of a quantum limited system. Over-estimation of [Formula: see text] was presumed to be a result of bias error due to temporally variable non-stationary noise. Statistical theory which allows for independent contributions of 'signal' from a test object (o) and temporally variable non-stationary noise (ns) was developed. The theory demonstrates that the biased [Formula: see text] is the sum of the detectability indices associated with the test object [Formula: see text] and non-stationary noise ([Formula: see text]). Given the nature of the imaging system and the experimental methods, [Formula: see text] cannot be directly determined independent of [Formula: see text]. However, methods to estimate [Formula: see text] independent of [Formula: see text] were developed. In accordance with the theory, [Formula: see text] was subtracted from experimental estimates of [Formula: see text], providing an unbiased estimate of [Formula: see text]. Estimates of [Formula: see text] exhibited trends consistent with expectations of an angiography system that is quantum limited for high DTD and compromised by detector electronic readout noise for low DTD conditions. Results suggest that these methods provide [Formula: see text] estimates which are accurate and precise for [Formula: see text]. Further, results demonstrated that the source of bias was detector electronic readout noise. In summary, this work presents theory and methods to test for the presence of bias in Hotelling model observers due to temporally variable non-stationary noise and correct this bias when the temporally variable non-stationary noise is independent and additive with respect to the test object signal. PMID- 27385087 TI - Simulation and Experiments To Identify Factors Allowing Synthetic Control of Structural Features of Polymeric Nanoparticles. AB - To develop a detailed picture of the microscopic structure of gelcore star polymers and to elucidate parameters of the synthetic process that might be exploited to control this structure, simulations of their synthesis were performed that were based on a particular synthetic approach. A range of results was observed from gelation at high reactant concentrations to the formation of various sizes and compositions of star polymers. Contrary to the prevailing experimental viewpoint, the simulations always suggest the production of a broad distribution of star polymer sizes. However, the GPC traces computed from simulation results are in good qualitative agreement with experiment. Topologically, the gelcore star polymers produced by simulation are not compact but, rather, sparse blobs loosely connected by filaments of linker when modeled in a good solvent. This is reflected in scaling relationships that relate polymer size (e.g., radius of gyration) and degree of polymerization. The arm-core composition is observed to be stoichiometric, strongly reflecting relative reactant concentrations during the synthesis. Reactions within star polymers that result in greater intramolecular cross-linking compete with those between star polymers that result in the production of larger star polymers from the joining of smaller ones. The balance in this competition can be controlled through the overall reactant concentration to limit and control resulting star polymer size. Therefore, the mean size, as well as the mean number of arms, can be controlled during synthesis by careful tuning of the overall ratio of the arm and linker reactant concentrations and the total reactant concentration. PMID- 27385088 TI - Age-related characteristics of risky decision-making and progressive expectation formation. AB - During daily encounters, it is inevitable that people take risks. Investigating the sequential processing of risk hazards involve expectation formation about outcome contingencies. The present study aimed to explore risk behavior and its neural correlates in sequences of decision making, particularly in old age, which represents a critical period regarding risk-taking propensity. The Balloon Analogue Risk Task was used in an electrophysiological setting with young and elderly age groups. During the task each additional pump on a virtual balloon increased the likelihood of a balloon burst but also increased the chance to collect more reward. Event-related potentials associated with rewarding feedback were analyzed based on the forthcoming decisions (whether to continue or to stop) in order to differentiate between states of expectation towards gain or loss. In the young, the reward positivity ERP component increased as a function of reward contingencies with the largest amplitude for rewarding feedback followed by the decision to stop. In the elderly, however, reward positivity did not reflect the effect of reward structure. Behavioral indices of risk-taking propensity suggest that the performance of the young and the elderly were dissociable only with respect to response times: The elderly was characterized by hesitation and more deliberative decision making throughout the experiment. These findings signify that sequential tracking of outcome contingencies has a key role in cost efficient action planning and progressive expectation formation. PMID- 27385089 TI - Synthesis and applications of rhodacyclopentanones derived from C-C bond activation. AB - Rhodacyclopentanones, an "sp(3)-rich" class of metallacycle, underpin an emerging range of catalytic methodologies for the direct generation of complex scaffolds. This review highlights strategies for accessing rhodacyclopentanones (and related species) by C-C bond activation of cyclobutanones or cyclopropanes. The scope and mechanism of methodologies that exploit these activation modes is outlined. PMID- 27385090 TI - Large vessel involvement in biopsy-proven giant cell arteritis: incidence, distribution, and predictors. AB - OBJECTIVES: Giant cell arteritis (GCA) is a systemic disease with extensive vascular involvement. The aim of this study was to investigate the cumulative incidence of large vessel involvement (LVI) in GCA, the distribution of vessels involved, and predictors for LVI. METHOD: Patients with biopsy-proven GCA in a defined area in southern Sweden, diagnosed between 1997 and 2010, were identified through the register of the regional Department of Clinical Pathology. A structured review of all medical records and imaging and histopathology reports was performed. Imaging studies for an age- and sex-matched reference cohort were also reviewed. RESULTS: A total of 164 patients with GCA were investigated, of whom 24 (15%) had LVI. LVI manifestations were detected a median of 3.7 [interquartile range (IQR) 0.7-7.5] years after GCA diagnosis. Aortic involvement was found in 16 patients (10%), mainly aneurysms/ectasias of the thoracic aorta. Two patients had aortic dissections. Fourteen patients had tributary involvement. In the reference population, the cumulative incidence of LVI overall was 10.8% and aortic involvement was found in 5.4%. The presence of giant cells in the biopsy was significantly less frequent among GCA patients with LVI (23% vs. 52%; p = 0.01), and a presentation with polymyalgia rheumatica (PMR) was more frequent (44% vs. 20%, p = 0.01). CONCLUSIONS: The estimated incidence of LVI, detected by imaging in a clinical setting, was higher among patients with GCA than the reference population. The aorta was the most commonly affected vascular territory. The negative association with giant cells may suggest particular mechanisms in this subset of GCA. PMID- 27385091 TI - Sex differences in stress-induced visceral hypersensitivity following early life adversity: a two hit model. AB - BACKGROUND: Early life adversity (ELA) has been indicated as a risk factor for the development of stress axis dysfunction in adulthood, specifically in females. We previously showed that unpredictable ELA induces visceral hyperalgesia in adult female rats. It remains to be determined whether ELA alters visceral nociceptive responses to stress in adulthood. The current study tested the hypothesis that following ELA, exposure to an adulthood stressor, or second hit, serves as a risk factor for exaggerated stress-induced visceral hypersensitivity that is sex-specific. METHODS: Following ELA, adult stress was induced via a single exposure (acute) or repetitive daily exposure, 1 h/day for 7 days (chronic), to water avoidance stress (WAS). KEY RESULTS: Acute WAS increased pain behaviors in all adult female rats, however, females that experienced unpredictable ELA exhibited significantly more pain behaviors compared to those exposed to predictable ELA or controls. Following chronic WAS, all adult females exhibited increased pain responses, however, an exaggerated response was observed in rats exposed to unpredictable or predictable ELA compared to controls. Similarly, in adult male rats exposure to acute or chronic WAS increased pain behaviors, however, there were no differences in pain behaviors between ELA groups. CONCLUSIONS & INFERENCES: This study highlights a novel consequence of ELA on stress-induced visceral nociception in adulthood that is sex-specific. More importantly, our study suggests that ELA not only serves as a risk factor for development of chronic pain in adulthood, but also serves as a predisposition for worsening of visceral pain following adult stress in female rats. PMID- 27385092 TI - Disruption of the EZH2/miRNA/beta-catenin signaling suppresses aerobic glycolysis in glioma. AB - EZH2 is up-regulated in various cancer types, implicating its role in tumorigenesis. Our recent data have shown that repression of EZH2 inhibited glioma growth by inhibition beta-catenin signaling. Here, we identified several miRNAs that were repressed by EZH2, which in turn regulate beta-catenin expression by its 3'UTR, such as miR-1224-3p, miR-328 and miR-214. Further, EZH2 silenced miR-328 expression by binding to miR-328 promoter and promoting methylation of miR-328 promoter. Finally, miR-328 largely abrogated EZH2 effects on beta-catenin expression and glucose metabolism in glioma cells. Taken together, we propose a model for a coordinated EZH2-beta-catenin oncoprotein axis, and epigenetic link between histone modification and DNA methylation, mediated by EZH2-scilenced miRNAs. PMID- 27385093 TI - TMPRSS4 induces invasion and proliferation of prostate cancer cells through induction of Slug and cyclin D1. AB - TMPRSS4 is a novel type II transmembrane serine protease found at the cell surface that is highly expressed in pancreatic, colon, and other cancer tissues. Previously, we demonstrated that TMPRSS4 mediates tumor cell invasion, migration, and metastasis. We also found that TMPRSS4 activates the transcription factor activating protein-1 (AP-1) to induce cancer cell invasion. Here, we explored TMPRSS4-mediated cellular functions and the underlying mechanisms. TMPRSS4 induced Slug, an epithelial-mesenchymal transition (EMT)-inducing transcription factor, and cyclin D1 through activation of AP-1, composed of c-Jun and activating transcription factor (ATF)-2, which resulted in enhanced invasion and proliferation of PC3 prostate cancer cells. In PC3 cells, not only c-Jun but also Slug was required for TMPRSS4-mediated proliferation and invasion. Interestingly, Slug induced phosphorylation of c-Jun and ATF-2 to activate AP-1 through upregulation of Axl, establishing a positive feedback loop between Slug and AP-1, and thus induced cyclin D1, leading to enhanced proliferation. Using data from The Cancer Genome Atlas, we found that Slug expression positively correlated with that of c-Jun and cyclin D1 in human prostate cancers. Expression of Slug was positively correlated with that of cyclin D1 in various cancer cell lines, whereas expression of other EMT-inducing transcription factors was not. This study demonstrates that TMPRSS4 modulates both invasion and proliferation via Slug and cyclin D1, which is a previously unrecognized pathway that may regulate metastasis and cancer progression. PMID- 27385095 TI - Tumor cells derived exosomes contain hTERT mRNA and transform nonmalignant fibroblasts into telomerase positive cells. AB - Exosomes are small (30-100nm) vesicles secreted from all cell types serving as inter-cell communicators and affecting biological processes in "recipient" cells upon their uptake. The current study demonstrates for the first time that hTERT mRNA, the transcript of the enzyme telomerase, is shuttled from cancer cells via exosomes into telomerase negative fibroblasts, where it is translated into a fully active enzyme and transforms these cells into telomerase positive, thus creating a novel type of cells; non malignant cells with telomerase activity. All tested telomerase positive cells, including cancer cells and non malignant cells with overexpressed telomerase secreted exosomal hTERT mRNA in accordance with the endogenous levels of their hTERT mRNA and telomerase activity. Similarly exosomes isolated from sera of patients with pancreatic and lung cancer contained hTERT mRNA as well. Telomerase activity induced phenotypic changes in the recipient fibroblasts including increased proliferation, extension of life span and postponement of senescence. In addition, telomerase activity protected the fibroblasts from DNA damage induced by phleomycin and from apoptosis, indicating that also telomerase "extracurricular" activities are manifested in the recipient cells. The shuttle of telomerase from cancer cells into fibroblasts and the induction of these changes may contribute to the alterations of cancer microenvironment and its role in cancer. The described process has an obvious therapeutic potential which will be explored in further studies. PMID- 27385096 TI - 5-FU targets rpL3 to induce mitochondrial apoptosis via cystathionine-beta synthase in colon cancer cells lacking p53. AB - Recent findings revealed in cancer cells novel stress response pathways, which in response to many chemotherapeutic drugs causing nucleolar stress, will function independently from tumor protein p53 (p53) and still lead to cell cycle arrest and/or apoptosis. Since it is known that most cancers lack functional p53, it is of great interest to explore these emerging molecular mechanisms. Here, we demonstrate that nucleolar stress induced by 5-fluorouracil (5-FU) in colon cancer cells devoid of p53 leads to the activation of ribosomal protein L3 (rpL3) as proapoptotic factor. rpL3, as ribosome-free form, is a negative regulator of cystathionine-beta-synthase (CBS) expression at transcriptional level through a molecular mechanism involving Sp1. The rpL3-CBS association affects CBS stability and, in addition, can trigger CBS translocation into mitochondria. Consequently apoptosis will be induced through the mitochondrial apoptotic cell death pathway characterized by an increased ratio of Bax to Bcl-2, cytochrome c release and subsequent caspase activation. It is noteworthy that silencing of CBS is associated to a strong increase of 5-FU-mediated inhibition of cell migration and proliferation. These data reveal a novel mechanism to accomplish p53-independent apoptosis and suggest a potential therapeutic approach aimed at upregulating rpL3 for treating cancers lacking p53. PMID- 27385097 TI - ARHGAP24 inhibits cell cycle progression, induces apoptosis and suppresses invasion in renal cell carcinoma. AB - Renal cell carcinoma (RCC) is the major cause of kidney malignancy-related deaths. Rho GTPases are key regulators in cancer cell metastasis. ARHGAP24, a Rac specific member of the Rho GTPase-activating protein family, acts as a functional target of cancer cell migration and invasion. In the present study, we identified ARHGAP24 expression is downregulated in renal cancer tissues and is highly correlated with long-term survival in RCC patients. Therefore, we investigated the biological functions of ARHGAP24 in renal cancer cells. Ectopic expression of ARHGAP24 resulted in inhibited cell proliferation and arrested cell cycle in two renal cancer cell lines (786-0 and Caki-2); the results were confirmed by ARHGAP24 knocking down. In addition, ARHGAP24 significantly reduced the cell invasion ability and induced apoptosis in renal cancer cells. In addition, overexpressing ARHGAP24 impaired tumor formation in vivo. In summary, our results illustrated that ARHGAP24 plays a unique role in RCC progression as a tumor repressor. PMID- 27385098 TI - TrkB-containing exosomes promote the transfer of glioblastoma aggressiveness to YKL-40-inactivated glioblastoma cells. AB - The neurotrophin receptors are known to promote growth and proliferation of glioblastoma cells. Their functions in spreading glioblastoma cell aggressiveness to the microenvironment through exosome release from glioblastoma cells are unknown. Considering previous reports demonstrating that YKL-40 expression is associated with undifferentiated glioblastoma cancer stem cells, we used YKL-40 silenced cells to modulate the U87-MG differentiated state and their biological aggressiveness. Herein, we demonstrated a relationship between neurotrophin receptors and YKL-40 expression in undifferentiated cells. Differential functions of cells and derived-exosomes were evidenced according to neurotrophin receptor content and differentiated cell state by comparison with control pLKO cells. YKL 40 silencing of glioblastoma cells impairs proliferation, neurosphere formation, and their ability to induce endothelial cell (HBMEC) migration. The modulation of differentiated cell state in YKL-40-silenced cells induces a decrease of TrkB, sortilin and p75NTR cellular expressions, associated with a low-aggressiveness phenotype. Interestingly, TrkB expressed in exosomes derived from control cells was undetectable in exosomes from YKL-40 -silenced cells. The transfer of TrkB containing exosomes in YKL-40-silenced cells contributed to restore cell proliferation and promote endothelial cell activation. Interestingly, in U87 MG xenografted mice, TrkB-depleted exosomes from YKL-40-silenced cells inhibited tumor growth in vivo. These data highlight that TrkB-containing exosomes play a key role in the control of glioblastoma progression and aggressiveness. Furthermore, TrkB expression was detected in exosomes isolated from plasma of glioblastoma patients, suggesting that this receptor may be considered as a new biomarker for glioblastoma diagnosis. PMID- 27385099 TI - The anti-cancer activity of the mTORC1/2 dual inhibitor XL388 in preclinical osteosarcoma models. AB - In the present study, we investigated the activity of XL388, a novel mammalian target of rapamycin (mTOR) complex 1/2 (mTORC1/2) dual inhibitor, in preclinical osteosarcoma (OS) models. XL388 was cytotoxic, cytostatic and pro-apoptotic to multiple established OS cell lines and primary human OS cells. XL388 blocked mTORC1/2 activation and downregulated cyclin D1/B1 expressions in OS cells, leaving AKT Thr-308 phosphorylation un-affected. Intriguingly, AKT1 T308A mutation potentiated XL388-induced cytotoxicity in OS cells. XL388 activated cytoprotective autophagy in OS cells. Autophagy inhibition, either pharmacologically or genetically, augmented XL388-induced anti-OS activity. Further, XL388 oral administration inhibited U2OS xenografts growth in severe combined immuno-deficient (SCID) mice. Such activity was enhanced with co administration of the autophagy inhibitor 3-methyladenine (3-MA). Similarly, Beclin-1-silenced U2OS xenografts were remarkably more sensitive to XL388. Thus, concurrent blockage of mTORC1/2 with XL388 may have therapeutic value for OS. PMID- 27385100 TI - Smac mimetic induces cell death in a large proportion of primary acute myeloid leukemia samples, which correlates with defined molecular markers. AB - Apoptosis is deregulated in most, if not all, cancers, including hematological malignancies. Smac mimetics that antagonize Inhibitor of Apoptosis (IAP) proteins have so far largely been investigated in acute myeloid leukemia (AML) cell lines; however, little is yet known on the therapeutic potential of Smac mimetics in primary AML samples. In this study, we therefore investigated the antileukemic activity of the Smac mimetic BV6 in diagnostic samples of 67 adult AML patients and correlated the response to clinical, cytogenetic and molecular markers and gene expression profiles. Treatment with cytarabine (ara-C) was used as a standard chemotherapeutic agent. Interestingly, about half (51%) of primary AML samples are sensitive to BV6 and 21% intermediate responsive, while 28% are resistant. Notably, 69% of ara-C-resistant samples show a good to fair response to BV6. Furthermore, combination treatment with ara-C and BV6 exerts additive effects in most samples. Whole-genome gene expression profiling identifies cell death, TNFR1 and NF-kappaB signaling among the top pathways that are activated by BV6 in BV6-sensitive, but not in BV6-resistant cases. Furthermore, sensitivity of primary AML blasts to BV6 correlates with significantly elevated expression levels of TNF and lower levels of XIAP in diagnostic samples, as well as with NPM1 mutation. In a large set of primary AML samples, these data provide novel insights into factors regulating Smac mimetic response in AML and have important implications for the development of Smac mimetic-based therapies and related diagnostics in AML. PMID- 27385101 TI - Clinical significance and diagnostic value of serum CEA, CA19-9 and CA72-4 in patients with gastric cancer. AB - AIMS: To evaluate the clinical significance of multiple serum tumor markers (TMs) in the diagnosis of gastric cancer (GC) and establish an accurate discriminant equation to identify the presence of GC. RESULTS: The serum levels of CEA, CA19-9 and CA72-4 were higher in the GC group than in the control group (P < 0.005). The sensitivity of CEA, CA19-9 and CA72-4 in the diagnosis of GC was 20.1-27.6% individually and increased to 48.2% when they were considered in combination. By using the optimal cut-off value, the sensitivity of CEA, CA19-9 and CA72-4 for the diagnosis of GC was improved but remained unsatisfactory. In addition, we developed the equation Y = -2.185 - 0.015 X1 + 0.180 X2 + 1.226 X3 + 1.505 X4 + 2.749 X5 (X1 = Age, X2 = Sex, X3 =CEA, X4 = CA19-9 and X5 = CA72-4) to predict the presence of GC. This has better accuracy and diagnostic efficiency compared to the combination of TMs. METHODS: Serum carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9)and cancer antigen 72-4 (CA72-4) levels were measured in a total of 2288 patients with GC and 1869 healthy volunteers or patients with benign gastric diseases. We established a diagnostic equation using a portion of the data (training set), and validate its accuracy using the other portion of the data (testing set) . CONCLUSIONS: The diagnostic equation increases the accuracy rate for the diagnosis of GC and will be helpful in the clinic. PMID- 27385102 TI - Immunotherapy for opportunistic infections: Current status and future perspectives. AB - The outcome after allogeneic haematopoietic stem cell transplantation (allo-HSCT) has significantly improved during the last decades. However, opportunistic infections such as viral and mold infections are still a major obstacle for cure. Within this field, adoptive T cell therapy against pathogens is a promising treatment approach. Recently, the techniques to develop T cell products including pathogen-specific T cells have been sophisticated and are now available in accordance to good manufacturing practice (GMP). Here, we aim to summarize current knowledge about adoptive T cell therapy against viral and mold infections. PMID- 27385103 TI - Analysis of chromosomal aberrations and recombination by allelic bias in RNA-Seq. AB - Genomic instability has profound effects on cellular phenotypes. Studies have shown that pluripotent cells with abnormal karyotypes may grow faster, differentiate less and become more resistance to apoptosis. Previously, we showed that microarray gene expression profiles can be utilized for the analysis of chromosomal aberrations by comparing gene expression levels between normal and aneuploid samples. Here we adopted this method for RNA-Seq data and present eSNP Karyotyping for the detection of chromosomal aberrations, based on measuring the ratio of expression between the two alleles. We demonstrate its ability to detect chromosomal gains and losses in pluripotent cells and their derivatives, as well as meiotic recombination patterns. This method is advantageous since it does not require matched diploid samples for comparison, is less sensitive to global expression changes caused by the aberration and utilizes already available gene expression profiles to determine chromosomal aberrations. PMID- 27385104 TI - Building a sustainable workforce in a rural and remote health service: A comprehensive and innovative Rural Generalist training approach. AB - BACKGROUND: Historically it has been challenging to recruit and retain an appropriately trained medical workforce to care for rural and remote Australians. This paper describes the Queensland North West Hospital and Health Service (NWHHS) workforce redesign, developing education strategies and pathways to practice, thereby improving service provision, recruitment and retention of staff. CONCEPT: The Mount Isa-based Medical Education Unit sought accreditation for a Rural Generalist (RG) training pathway from Internship to Fellowship with the Australian College of Rural and Remote Medicine (ACRRM) and the Regional Training Provider (RTP). This approach enhanced the James Cook University (JCU) undergraduate pathway for rurally committed students while improving recruitment and retention of RMOs/Registrars. ACHIEVEMENTS: Accreditation was achieved through collaboration with training providers, accreditation agencies, ACRRM and a local general practice. The whole pathway from ignore Internship to Fellowship is offered with the RG Intern intake as a primary allocation site beginning in 2016. Comprehensive supervision and excellent clinical exposure provide an interesting and rewarding experience - for staff at all levels. RESULTS: Since 2013 RMO locum rates have been <1%. Registrars on the ACRRM pathway and Interns increased from 0 to 7 positions each in 2015, with similar achievements in SMO staffing. Three RMOs expressed interest in a Registrar position, CONCLUSIONS: Appropriate governance is needed to develop and advertise the program. This includes the NWHHS, the RG Pathway and JCU. PMID- 27385105 TI - Practical execution of defect preparation prior to surgical cartilage intervention: results from a representative meeting survey among experts. AB - During a specialised orthopedic meeting held on 'the state of the art in cartilage defect repair', all previously fully-registered participants were requested to participate in an electronic survey by the use of a moderator presented "Power Point Presentation-based" 9-item questionnaire. The aim of this survey was to assess indication, approach, and treatment execution of cartilage defect debridement prior to planned microfracture (MFX) or autologous chondrocyte implantation (ACI). All participants completed the questionnaire (n = 146) resulting in a return rate of 100 %. An uncertainty exists as to whether the removal of the calcifying layer prior to cartilage repair must be carried out or not. The same was true for the acceptability of subchondral bleeding prior to microfracturing and its handling prior to autologous chondrocyte implantation. There is a degree of unanimity among experts regarding the management of osteophytes and bone marrow edema. In a homogenous society collective of consultants that frequently deal with cartilage defective pathologies, there still remain a significant heterogeneity in selected topics of defect debridement. PMID- 27385106 TI - Proteome analysis of adrenal cortical tumors. AB - INTRODUCTION: Adrenal tumor is a relatively common tumor. The discrimination between adrenal cortical adenoma (ACA) and adrenal cortical carcinoma (ACC) is crucial as these two diseases have distinct prognosis. ACA is a benign tumor curable by surgical excision, while the prognosis of ACC is extremely poor, with a 5-year mortality of 75-90%. Therefore, previous proteomic studies focused on markers allowing the differentiation between ACA and ACC. AREAS COVERED: Several proteomic approaches based on the analysis of various samples such as human tissues, urine, and cell lines. In this review, we focused on proteomic studies performed to improve adrenal tumor diagnosis and identify ACC therapeutic targets. Expert commentary: The rapid development of cancer genomics provided a lot of information, which affects functional proteomics. In practice, differentially expressed proteins between ACA and ACC have been suggested in several proteomic studies and had a biologic implication in ACC. PMID- 27385108 TI - [Ethnic nail pigmentations and differential diagnoses]. AB - Pigmentary nail changes may have a variety of causes, e. g., chronic inflammation, and occur more often in patients of African descent compared to Caucasians. Subungual malignant melanoma is the most important differential diagnosis and must be ruled out in any case. Dermatoscopy might be helpful. If no biopsy is taken, clinical follow-ups are necessary at short intervals. In case of chronic paronychia, optimization of occupational skin protection measures may contribute to the healing process. PMID- 27385107 TI - Complex Ancestries of Lager-Brewing Hybrids Were Shaped by Standing Variation in the Wild Yeast Saccharomyces eubayanus. AB - Lager-style beers constitute the vast majority of the beer market, and yet, the genetic origin of the yeast strains that brew them has been shrouded in mystery and controversy. Unlike ale-style beers, which are generally brewed with Saccharomyces cerevisiae, lagers are brewed at colder temperatures with allopolyploid hybrids of Saccharomyces eubayanus x S. cerevisiae. Since the discovery of S. eubayanus in 2011, additional strains have been isolated from South America, North America, Australasia, and Asia, but only interspecies hybrids have been isolated in Europe. Here, using genome sequence data, we examine the relationships of these wild S. eubayanus strains to each other and to domesticated lager strains. Our results support the existence of a relatively low diversity (pi = 0.00197) lineage of S. eubayanus whose distribution stretches across the Holarctic ecozone and includes wild isolates from Tibet, new wild isolates from North America, and the S. eubayanus parents of lager yeasts. This Holarctic lineage is closely related to a population with higher diversity (pi = 0.00275) that has been found primarily in South America but includes some widely distributed isolates. A second diverse South American population (pi = 0.00354) and two early-diverging Asian subspecies are more distantly related. We further show that no single wild strain from the Holarctic lineage is the sole closest relative of lager yeasts. Instead, different parts of the genome portray different phylogenetic signals and ancestry, likely due to outcrossing and incomplete lineage sorting. Indeed, standing genetic variation within this wild Holarctic lineage of S. eubayanus is responsible for genetic variation still segregating among modern lager-brewing hybrids. We conclude that the relationships among wild strains of S. eubayanus and their domesticated hybrids reflect complex biogeographical and genetic processes. PMID- 27385109 TI - [Sports-associated dermatophytoses : An overview]. AB - Because of high exposure (e. g. swimmers and athletes competing on mats) and disposition (e. g. microtraumata of the skin in runners) athletes are prone to a higher risk for mycotic infections by dermatophytes. In disciplines with close contact during competition-especially wrestlers and judoists-infections by the anthropophilic Trichophyton (T.) tonsurans are most important (tinea gladiatorum). These infections are highly contagious and often cause small epidemics especially if the primary source of infection is not promptly recognized. The environment of the athletes (e. g. mats) and asymptomatic carriers may be sources of further spread. Tinea pedis with its clinical manifestations seems to be often underdiagnosed and insufficiently treated. Environmental contamination by fungal spores may be responsible for the significantly higher level of mycotic infections of the feet in children and adolescents active in sports. There is a higher risk for spread of the infection to the toe nails (onychomycosis) and for consecutive infections by bacteria (e. g. erysipelas). More rarely infections by zoophilic or geophilic dermatophytes are seen in athletes (e.g. equestrians). Education and more intensive measures of prevention and environmental decontamination are essential for all dermatophytoses associated with sports. PMID- 27385110 TI - A national survey on the use of screening tools to detect physical child abuse. AB - PURPOSE: Recognition of physical child abuse is imperative for ensuring children's safety. Screening tools (ST) may increase identification of physical abuse; however, the extent of their use is unknown. This study assessed use of STs for physical abuse in children's hospitals and determined attitudes regarding STs. METHODS: A web-based survey was sent to child abuse program contacts at 103 children's hospitals. The survey assessed institutional use of a ST for physical abuse and characteristics of the ST used. Respondents were asked to identify benefits and liabilities of STs used or barriers to ST use. RESULTS: Seventy-two respondents (70 %) completed the survey; most (64 %) were child abuse pediatricians. Nine (13 %) respondents reported using a ST for physical abuse; STs varied in length, population, administration, and outcomes of a positive screen. Most respondents (86 %) using a ST felt that it increased detection of abuse. Barriers noted included lack of time for development and provider completion of a ST. CONCLUSIONS: While few respondents endorsed use of a ST for physical abuse, most believed that it increased detection of abuse. Future research should focus on development of a brief, uniform ST for physical abuse which may increase detection in at-risk children. PMID- 27385112 TI - Utilisation of aromatic organosulfur compounds as sulfur sources by Lipomyces starkeyi CBS 1807. AB - Aromatic organosulfur compounds that contain aryl carbon-sulfur bonds are rare in nature but occur frequently in industrial processes and products. The utilisation of aryl sulfur compounds as a sulfur source has not been described previously among the budding yeasts (phylum Ascomycota, sub-phylum Saccharomycotina). A total of 31 strains representing 30 species and 28 genera of the budding yeasts were assayed for utilisation of benzene sulfonate as source of sulfur. Lipomyces starkeyi CBS 1807 was the only strain in this screen that was able to utilise benzene sulfonate as a sulfur source. Further study of L. starkeyi demonstrated that it could also utilise methyl phenyl sulfoxide, 1-naphthalene sulfonate, 2 naphthalene sulfonate, 1-anthraquinone sulfonate and 2-anthraquinone sulfonate as sulfur sources but not diphenylsulfone. This study represents the first reported case of the utilisation of sulfonated naphthalenes and anthraquinones as sulfur sources by a fungus. However, it should be stressed that the remaining 30 strains in this study were not assayed for the utilisation of these additional aryl sulfur compounds as sulfur sources. The present study highlights the potential of L. starkeyi and related species as a source of novel enzyme activities with possible applications in chemical manufacturing, disposal of xenobiotics and bioremediation. PMID- 27385113 TI - Missing concepts in natural selection theory reconstructions. AB - The concept of fitness has generated a lot of discussion in philosophy of biology. There is, however, relative agreement about the need to distinguish at least two uses of the term: ecological fitness on the one hand, and population genetics fitness on the other. The goal of this paper is to give an explication of the concept of ecological fitness by providing a reconstruction of the theory of natural selection in which this concept was framed, that is, based on the way the theory was put to use in Darwin's main texts. I will contend that this reconstruction enables us to account for the current use of the theory of natural selection. The framework presupposed in the analysis will be that of metatheoretical structuralism. This framework will provide both a better understanding of the nature of ecological fitness and a more complete reconstruction of the theory. In particular, it will provide what I think is a better way of understanding how the concept of fitness is applied through heterogeneous cases. One of the major advantages of my way of thinking about natural selection theory is that it would not have the peculiar metatheoretical status that it has in other available views. I will argue that in order to achieve these goals it is necessary to make several concepts explicit, concepts that are frequently omitted in usual reconstructions. PMID- 27385111 TI - Long-term results of transanal pull-through for Hirschsprung's disease: a meta analysis. AB - INTRODUCTION: Several operative techniques have been developed for the treatment of Hirschsprung's disease (HD) in the past decades. Since one-stage transanal pull-through (TAPT) was first performed in 1998, multiple studies have shown favourable short-and midterm results compared to other techniques with shorter operation length, shorter hospital stay and lower complication rates. The aim of this meta-analysis was to determine the longterm results following TAPT for HD. METHODS: A systematic literature search for relevant articles was performed in four databases using the following terms "Hirschsprung/Hirschsprung's disease", "aganglionosis", "transanal", "pullthrough/pull-through", "longterm/long-term" "results", "follow-up" and "outcome". A meta-analysis was conducted for relevant articles for one-stage transanal pull-through for HD with a minimal follow-up of median 36 months regarding constipation, incontinence/soiling, enterocolitis and secondary operations. Odds ratio (OR) with 95 % confidence intervals (CI) were calculated. RESULTS: Six studies with 316 patients matched the set criteria and were included in this analysis. Overall 45 (14.2 %) patients had disturbances of bowel function (OR 0.05, 95 % CI 0.03-0.07, p < 0.00001). Of these, 24 (53.3 %) patients experienced constipation, 8 (17.8 %) incontinence/soiling and 13 (28.9 %) enterocolitis. 10 (3.2 %) patients developed complications requiring secondary surgery. Most patients had a daily defecation frequency of 1-3 bowel movements 3 years postoperatively, resembling the stooling patterns of healthy controls. CONCLUSION: Nearly 15 % of all patients operated with TAPT for HD continue to experience persistent bowel symptoms with constipation as the main problem. Further studies on the long-term outcome of children operated with this technique for HD are necessary to evaluate stooling patterns, urinary and sexual function as well as general quality of life during adolescence and adulthood. PMID- 27385114 TI - Teresa Ortiz-Gomez and Maria Jesus Santesmases (eds.), Gendered Drugs and Medicine: Historical and Socio-Cultural Perspectives : Ashgate Publishing, Farnham and Burlington VT, 2014. 246 pp. L65 (hard cover). PMID- 27385115 TI - Sixty seconds on . . . helium. PMID- 27385116 TI - Challenging the paradigms of leaf evolution: Class III HD-Zips in ferns and lycophytes. AB - Despite the extraordinary significance leaves have for life on Earth, their origin and development remain vigorously debated. More than a century of paleobotanical, morphological, and phylogenetic research has still not resolved fundamental questions about leaves. Developmental genetic data are sparse in ferns, and comparative studies of lycophytes and seed plants have reached opposing conclusions on the conservation of a leaf developmental program. We performed phylogenetic and expression analyses of a leaf developmental regulator (Class III HD-Zip genes; C3HDZs) spanning lycophytes and ferns. We show that a duplication and neofunctionalization of C3HDZs probably occurred in the ancestor of euphyllophytes, and that there is a common leaf developmental mechanism conserved between ferns and seed plants. We show C3HDZ expression in lycophyte and fern sporangia and show that C3HDZs have conserved expression patterns during initiation of lateral primordia (leaves or sporangia). This expression is maintained throughout sporangium development in lycophytes and ferns and indicates an ancestral role of C3HDZs in sporangium development. We hypothesize that there is a deep homology of all leaves and that a sporangium-specific developmental program was coopted independently for the development of lycophyte and euphyllophyte leaves. This provides molecular genetic support for a paradigm shift in theories of lycophyte leaf evolution. PMID- 27385117 TI - Reversine Induced Multinucleated Cells, Cell Apoptosis and Autophagy in Human Non Small Cell Lung Cancer Cells. AB - Reversine, an A3 adenosine receptor antagonist, has been shown to induce differentiated myogenic-lineage committed cells to become multipotent mesenchymal progenitor cells. We and others have reported that reversine has an effect on human tumor suppression. This study revealed anti-tumor effects of reversine on proliferation, apoptosis and autophagy induction in human non-small cell lung cancer cells. Treatment of these cells with reversine suppressed cell growth in a time- and dosage-dependent manner. Moreover, polyploidy occurred after reversine treatment. In addition, caspase-dependent apoptosis and activation of autophagy by reversine in a dosage-dependent manner were also observed. We demonstrated in this study that reversine contributes to growth inhibition, apoptosis and autophagy induction in human lung cancer cells. Therefore, reversine used as a potential therapeutic agent for human lung cancer is worthy of further investigation. PMID- 27385118 TI - The feet in systemic lupus erythematosus; are we underestimating their involvement and functional impact? AB - OBJECTIVES: To evaluate biomechanical and ultrasound (US) abnormalities in SLE patients as compared with controls and to assess the relationship between these abnormalities and SLE activity. METHODS: Fifty-four consecutive female patients with SLE with and without foot pain and 60 female controls (30 with foot pain and 30 without foot pain) were recruited. SLE activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). SLE patients and controls blindly underwent a comprehensive podiatric, biomechanical and US evaluation of the feet. US assessment included detection of B-mode synovitis, tenosynovitis, enthesopathy, bone changes and synovial, tenosynovial and entheseal power Doppler (PD) signal. RESULTS: Thirty-one (57.4%) SLE patients had bilateral foot pain and 5 (9.3%) had unilateral foot pain. Metatarsalgia was the most common location for pain but without significant difference between groups (p=0.284). Toe joint deformities were significantly more common in SLE feet as compared with control feet (p<0.0005). SLE feet showed significantly more biomechanical abnormalities than control feet (p<0.05). B-mode synovitis in the tibiotalar joint was strongly associated with having SLE (p<0.0005) and the presence of synovial PD signal in the MTP joints was found only in painful feet of SLE patients. SLEDAI was significantly higher in patients with foot pain than in those with painless feet (p=0.008). However, SLEDAI did not discriminate between patients with and without biomechanical or US abnormalities. CONCLUSIONS: SLE patients showed more biomechanical and US abnormalities in the feet than controls, which were not captured by standardised assessment of the disease activity. PMID- 27385121 TI - Self-Tracking: Reflections from the BodyTrack Project. AB - Based on the author's experiences the practice of self-tracking can empower individuals to explore and address issues in their lives. This work is inspired by examples of people who have reclaimed their wellness through an iterative process of noticing patterns of ups and downs, trying out new ideas and strategies, and observing the results. In some cases, individuals have realized that certain foods, environmental exposures, or practices have unexpected effects for them, and that adopting custom strategies can greatly improve quality of life, overcoming chronic problems. Importantly, adopting the role of investigator of their own situation appears to be transformative: people who embarked on this path changed their relationship to their health situation even before making discoveries that helped lead to symptom improvement. The author co-founded the BodyTrack project in 2010 with the goal of empowering a broader set of people to embrace this investigator role in their own lives and better address their health and wellness concerns, particularly those with complex environmental or behavioral components. The core of the BodyTrack system is an open source web service called Fluxtream ( https://fluxtream.org ) that allows users to aggregate, visualize, and reflect on data from myriad sources on a common timeline. The project is also working to develop and spread peer coaching practices to help transfer the culture and skills of self-tracking while mentoring individuals in how to self-assess their own situation and guide the process for themselves. PMID- 27385119 TI - Re-evaluation of the mechanisms of dietary fibre and implications for macronutrient bioaccessibility, digestion and postprandial metabolism. AB - The positive effects of dietary fibre on health are now widely recognised; however, our understanding of the mechanisms involved in producing such benefits remains unclear. There are even uncertainties about how dietary fibre in plant foods should be defined and analysed. This review attempts to clarify the confusion regarding the mechanisms of action of dietary fibre and deals with current knowledge on the wide variety of dietary fibre materials, comprising mainly of NSP that are not digested by enzymes of the gastrointestinal (GI) tract. These non-digestible materials range from intact cell walls of plant tissues to individual polysaccharide solutions often used in mechanistic studies. We discuss how the structure and properties of fibre are affected during food processing and how this can impact on nutrient digestibility. Dietary fibre can have multiple effects on GI function, including GI transit time and increased digesta viscosity, thereby affecting flow and mixing behaviour. Moreover, cell wall encapsulation influences macronutrient digestibility through limited access to digestive enzymes and/or substrate and product release. Moreover, encapsulation of starch can limit the extent of gelatinisation during hydrothermal processing of plant foods. Emphasis is placed on the effects of diverse forms of fibre on rates and extents of starch and lipid digestion, and how it is important that a better understanding of such interactions with respect to the physiology and biochemistry of digestion is needed. In conclusion, we point to areas of further investigation that are expected to contribute to realisation of the full potential of dietary fibre on health and well-being of humans. PMID- 27385120 TI - HCV RNA Activates APCs via TLR7/TLR8 While Virus Selectively Stimulates Macrophages Without Inducing Antiviral Responses. AB - The innate and adaptive immune systems fail to control HCV infection in the majority of infected individuals. HCV is an ssRNA virus, which suggests a role for Toll-like receptors (TLRs) 7 and 8 in initiating the anti-viral response. Here we demonstrate that HCV genomic RNA harbours specific sequences that initiate an anti-HCV immune response through TLR7 and TLR8 in various antigen presenting cells. Conversely, HCV particles are detected by macrophages, but not by monocytes and DCs, through a TLR7/8 dependent mechanism; this leads to chloroquine sensitive production of pro-inflammatory cytokines including IL 1beta, while the antiviral type I Interferon response is not triggered in these cells. Antibodies to DC-SIGN, a c-type lectin selectively expressed by macrophages but not pDCs or mDCs, block the production of cytokines. Novel anti HCV vaccination strategies should target the induction of TLR7/8 stimulation in APCs in order to establish potent immune responses against HCV. PMID- 27385122 TI - Copy-Paste: 2-Click Step to Success and Productivity that Underlies Self Plagiarism. PMID- 27385123 TI - Facilitators of Survivorship Care Among Underserved Breast Cancer Survivors: a Qualitative Study. AB - Research investigating facilitators of survivorship care among underserved breast cancer survivors (BCS) is sparse. This study aimed to explore facilitators of survivorship care among underserved BCS within the first 5 years following chemotherapy, radiation, or surgery for breast cancer. In-depth interviews were conducted, using a semi-structured interview guide, with underserved BCS exploring survivorship care experiences. Content analysis of the verbatim transcripts was applied, and results were summarized according to themes related to facilitators of breast cancer survivorship care. Interviews were conducted with 25 BCS. Eight main themes were identified: coordination of care; positive perceptions of health care providers; communication between patient and health care providers; financial and insurance facilitators; information, classes, and programs provided; assistance provided by organizations and health care professionals; transportation facilitators; and job flexibility. This study provides a comprehensive look at facilitators of survivorship care among underserved BCS. BCS endorsed several facilitators of their survivorship care, mainly at the interpersonal, organizational, and societal level. This study adds to the research literature on catalysts of care among underserved BCS. Results from this study are currently being used to inform a patient navigation intervention to facilitate care among this population. PMID- 27385124 TI - A pilot study evaluating the use of cervical ultrasound to confirm endotracheal intubation in dogs. AB - OBJECTIVE: To assess the accuracy and usability of cervical ultrasound as a means to confirm endotracheal (ET) intubation in dogs. DESIGN: Randomized pilot study. SETTING: University teaching hospital. ANIMALS: Six recently euthanized cadaver dogs. INTERVENTIONS: Endotracheal and esophageal intubations were randomly performed. The investigators performing the ultrasound examinations were blinded to the type of intubation. Ultrasound examinations were performed in right and left lateral recumbency. The time taken to obtain the images was recorded. MEASUREMENTS AND MAIN RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value with their correspondent 95% confidence intervals (CI) were 91.7% (CI, 82.7-96.7), 72.7% (CI, 60.4-84.0%), 78.6% (CI, 68.3-86.8%), and 88.9% (CI, 77.4-95.8%), respectively. The overall test accuracy with its correspondent 95% CI was 82.8% (CI, 75.4-88.1%). The mean time for confirmation with ultrasound was 20.2 seconds (standard deviation, 14.3 s). Cervical ultrasound was significantly more accurate at recognizing ET intubations than esophageal intubations (odds ratio, 4.52; 95% CI, 1.43-14.27; P = 0.010). There was a significant relationship between increase in body weight and accuracy, indicating that the test is more accurate in larger dogs (odds ratio, 1.04; 95% CI, 1.00-1.08; P = 0.042). CONCLUSIONS: Cervical ultrasound has high sensitivity and moderate specificity for ET intubation, and may be a useful tool to confirm ET intubation in dogs. PMID- 27385125 TI - Molecular evidence that exercise training has beneficial effects on cardiac performance. PMID- 27385126 TI - Epigenetic regulation in gallbladder cancer: Promoter methylation profiling as emergent novel biomarkers. AB - DNA methylation, once considered to rule the sex determination in Mary Lyon's hypothesis, has now reached the epicenter of human diseases, from monogenic (e.g. Prader Willi syndrome, Angelman syndromes and Beckwith-Wiedemann syndrome) to polygenic diseases, like cancer. Technological developments from gold standard to high throughput technologies have made tremendous advancement to define the epigenetic mechanism of cancer. Gallbladder cancer (GBC) is a fatal health issue affecting mostly the middle-aged women, whose survival rate is very low due to late symptomatic diagnosis. DNA methylation has become one of the key molecular mechanisms in the tumorigenesis of gallbladder. Various molecules have been reported to be epigenetically altered in GBC. In this review, we have discussed the classes of epigenetics, an overview of DNA methylation, technological approaches for its study, profile of methylated genes, their likely roles in GBC, future prospects of biomarker development and other discovery approaches, including therapeutics. PMID- 27385129 TI - Supramolecular Recognition Induces Nonsynchronous Change of Dye Fluorescence Properties. AB - Fluorescence behavior of 8-anilino-1-naphthalenesulfonate (ANS) reflects a blue shift and fluorescence enhancement on decreasing solvent polarity, with both properties affected in a synchronous way in solvent mixtures where ANS senses a homogeneous solvation shell. ANS complexation by cyclodextrins or bovine serum albumin (BSA) results in a nonhomogeneous solvation shell that is reflected by nonsynchronous variation of fluorescence properties. Steady-state fluorescence and saturation transfer difference NMR experiments allow us to conclude the formation of 1:1 and 2:1 host/guest complexes through the aniline or naphthalene moieties of ANS with cyclodextrins. This nonhomogeneous solvation shell has been ignored in studies using ANS to sense the microenvironment of proteins, micelles, bilayers, and other organized systems. ANS interaction with BSA reflects the existence of a large number of binding pockets in the surface of the protein that can be classified into two well-differentiated categories. PMID- 27385127 TI - Reduced sterol regulatory element-binding protein (SREBP) processing through site 1 protease (S1P) inhibition alters oligodendrocyte differentiation in vitro. AB - The formation of the myelin membrane of the oligodendrocyte in the CNS is a fundamental process requiring the coordinated synthesis of many different components. The myelin membrane is particularly rich in lipids, however, the regulation of this lipid synthesis is not understood. In other cell types, including Schwann cells, the myelin-forming cells of the PNS, lipid synthesis is tightly regulated by the sterol regulatory element-binding protein (SREBP) family of transcription factors, but this has not been previously shown in oligodendrocytes. We investigated SREBPs' role during oligodendrocyte differentiation in vitro. Both SREBP-1 and SREBP-2 were expressed in oligodendrocyte precursor cells and differentiating oligodendrocytes. Using the selective site-1 protease (S1P) inhibitor PF-429242, which inhibits the cleavage of SREBP precursor forms into mature forms, we found that preventing SREBP processing inhibited process growth and reduced the expression level of myelin basic protein, a major component of myelin. Further, process extension deficits could be rescued by the addition of exogenous cholesterol. Blocking SREBP processing reduced mRNA transcription and protein levels of SREBP target genes involved in both the fatty acid and the cholesterol synthetic pathways. Furthermore, de novo levels and total levels of cholesterol synthesis were greatly diminished when SREBP processing was inhibited. Together these results indicate that SREBPs are important regulators of oligodendrocyte maturation and that perturbation of their activity may affect myelin formation and integrity. Cover Image for this issue: doi: 10.1111/jnc.13781. PMID- 27385130 TI - Graph Theoretical Analysis of Structural Neuroimaging in Temporal Lobe Epilepsy with and without Psychosis. AB - PURPOSE: Psychosis is one of the most important psychiatric comorbidities in temporal lobe epilepsy (TLE), and its pathophysiology still remains unsolved. We aimed to explore the connectivity differences of structural neuroimaging between TLE with and without psychosis using a graph theoretical analysis, which is an emerging mathematical method to investigate network connections in the brain as a small-world system. MATERIALS AND METHODS: We recruited 11 TLE patients with unilateral hippocampal sclerosis (HS) presenting psychosis or having a history of psychosis (TLE-P group). As controls, 15 TLE patients with unilateral HS without any history of psychotic episodes were also recruited (TLE-N group). For graph theoretical analysis, the normalized gray matter images of both groups were subjected to Graph Analysis Toolbox (GAT). As secondary analyses, each group was compared to 14 age- and gender-matched healthy subjects. RESULTS: The hub node locations were found predominantly in the ipsilateral hemisphere in the TLE-N group, and mainly on the contralateral side in the TLE-P group. The TLE-P group showed significantly higher characteristic path length, transitivity, lower global efficiency, and resilience to random or targeted attack than those of the TLE-N group. The regional comparison in betweenness centrality revealed significantly decreased connectivity in the contralateral temporal lobe, ipsilateral middle frontal gyrus, and bilateral postcentral gyri in the TLE-P group. The healthy subjects showed well-balanced nodes/edges distributions, similar metrics to TLE-N group except for higher small worldness/modularity/assortativity, and various differences of regional betweenness/clustering. CONCLUSION: In TLE with psychosis, graph theoretical analysis of structural imaging revealed disrupted connectivity in the contralateral hemisphere. The network metrics suggested that the existence of psychosis can bring vulnerability and decreased efficiency of the whole-brain network. The sharp differences in structural networks between morphologically homogeneous groups are remarkable and may contribute to a better understanding of psychosis in TLE. PMID- 27385132 TI - Deriving the reference value from the circadian motor active patterns in the "non dementia" population, compared to the "dementia" population: What is the amount of physical activity conducive to the good circadian rhythm. AB - BACKGROUND: The circadian rhythm in older adults is commonly known to change with a decrease in physical activity. However, the association between circadian rhythm metrics and physical activity remains unclear. The objective of this study was to examine circadian activity patterns in older people with and without dementia and to determine the amount of physical activity conducive to a good circadian measurement. METHOD: Circadian parameters were collected from 117 older community-dwelling people (66 subjects without dementia and 52 subjects with dementia); the parameters were measured continuously using actigraphy for 7 days. A receiver operating characteristic (ROC) curve was applied to determine reference values for the circadian rhythm parameters, consisting of interdaily stability (IS), intradaily variability (IV), and relative amplitude (RA), in older subjects. RESULTS: The ROC curve revealed reference values of 0.55 for IS, 1.10 for IV, and 0.82 for RA. In addition, as a result of the ROC curve in the moderate-to-vigorous physical Activity (MVPA) conducive to the reference value of the Non-parametric Circadian Rhythm Analysis per day, the optimal reference values were 51 minutes for IV and 55 minutes for RA. However, the IS had no classification accuracy. CONCLUSIONS: Our results demonstrated the reference values derived from the circadian parameters of older Japanese population with or without dementia. Also, we determined the MVPA conducive to a good circadian rest active pattern. This reference value for physical activity conducive to a good circadian rhythm might be useful for developing a new index for health promotion in the older community-dwelling population. PMID- 27385133 TI - The functional results of radical rectal cancer surgery: review of the literature. AB - Introduction For more than the last 20 years, low anterior resection with total mesorectal excision (TME) is a gold standard for rectal cancer treatment. Oncological outcomes have improved significantly and now more and more reports of functional outcomes appear. Due to the close relationship between the rectum and pelvic nerves, bowel, bladder, and sexual function are frequently affected during TME. Methods A search for published data was performed using the MEDLINE database (from 1 January 2005 to 31 January 2015) to perform a systematic review of the studies that described anorectal, bladder, and sexual dysfunction following rectal cancer surgery. Methodological quality of the included studies was assessed using the MINORS criteria. Results Eighty-nine studies were eligible for analysis. Up to 76% of patients undergoing sphincter preserving surgery will have changes in bowel habits, the so-called "low anterior resection syndrome" (LARS). The duration of LARS varies between a few months and several years. Pre-operative radiotherapy, damage of anal sphincter and pelvic nerves, and height of the anastomosis are the risk factors for LARS. There is no evidence-based treatment available for LARS. Sexual function is more commonly affected after rectal surgery than after urinary function. The main cause of dysfunction is damage to pelvic nerves. Sexual and bladder functional outcomes in females are less well reported. Laparoscopic and robotic surgery allows better visualization of autonomic nerves and, therefore, more precise dissection and preservation. Conclusions It is important that rectal resection is standardized as much as possible, and that new functional outcome research use the same validated outcome questionnaires. This would allow for a high-quality meta-analysis. PMID- 27385134 TI - Massive bleeding following severe blunt trauma: the first minutes that can change everything. AB - The first hour following a major trauma with massive bleeding is certainly the most decisive period in global trauma care. Most of it takes place during the prehospital care. Those prehospital minutes are thus determinant as they can be used to correctly identified patient's clinical condition, initiate organization of the in-hospital needed resources and initiate specific therapies in the very early phase after trauma. Significant recent advances in this aspect of care have been made and but evidence to support some of those strategies is still lacking. PMID- 27385131 TI - The transcriptomes of novel marmoset monkey embryonic stem cell lines reflect distinct genomic features. AB - Embryonic stem cells (ESCs) are useful for the study of embryonic development. However, since research on naturally conceived human embryos is limited, non human primate (NHP) embryos and NHP ESCs represent an excellent alternative to the corresponding human entities. Though, ESC lines derived from naturally conceived NHP embryos are still very rare. Here, we report the generation and characterization of four novel ESC lines derived from natural preimplantation embryos of the common marmoset monkey (Callithrix jacchus). For the first time we document derivation of NHP ESCs derived from morula stages. We show that quantitative chromosome-wise transcriptome analyses precisely reflect trisomies present in both morula-derived ESC lines. We also demonstrate that the female ESC lines exhibit different states of X-inactivation which is impressively reflected by the abundance of the lncRNA X inactive-specific transcript (XIST). The novel marmoset ESC lines will promote basic primate embryo and ESC studies as well as preclinical testing of ESC-based regenerative approaches in NHP. PMID- 27385135 TI - Early myotomy and fundoplication in achalasia in childhood: a single-centre experience for 22 years. AB - Introduction The aim of this study was to review a single institution's experience with surgical interventions in children with achalasia and to determine treatment strategies for this rare disorder. Patients and methods This study is a retrospective analysis of 22 cases of childhood achalasia from 1991 to 2013. The patients were evaluated in terms of age, symptoms, interventions, intraoperative complications, and recurrent dysphagia. Results There were 13 boys and nine girls (7 months to 17 years old). The clinical symptoms were vomiting (68%), dysphagia (36%), wheezing (18%), coughing (13%), and weight-loss (13%). The mean duration of symptoms was 2.4 years (1 month to 6 years). A barium contrast X-ray study was performed in all of the patients. Oesophageal manometry was performed in eight patients. Six patients underwent multiple oesophageal dilatations (ED) as a first intervention. A Heller myotomy (HM) and fundoplication were performed in all the patients except two patients who recovered with dilatation. In the long term, one patient had a stricture due to the operation and had to undergo a reoperation. Of the Heller myotomy patients, one had a recurrent stricture that responded to dilatation. No other complications were present. All the patients are now asymptomatic. Conclusion Early diagnosis and prompt surgical treatment is important to prevent growth impairment in childhood achalasia cases. A Heller myotomy followed by a partial anti-reflux procedure is an effective treatment for achalasia in children. Based on our experience, it is superior to oesophageal dilatation therapy. PMID- 27385136 TI - Evaluation of cisplatin plasma levels in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. AB - Introduction Peritoneal surface malignancies have long been regarded as incurable, however, they can be treated with cytoreductive surgery in addition to hyperthermic intraperitoneal chemotherapy. This approach is associated with an increase in morbidity and mortality, unless hyperhydration is provided in a timely manner. Methods Cisplatin (CDDP) is the most widely used chemotherapeutic agent. Plasma levels of cisplatin (CDDP), a widely used chemotherapeutic agent, were measured before, during, and after the procedure. This was done in order to identify the window of highest risk as a function of drug concentrations, assuming a dose-dependent effect. Results Plasma levels of CDDP peak during perfusion. The concentration remains high until the 4th post-operative day and returns to pre-operative levels by the 7th post-operative day. Conclusions Our findings suggest that ensuring hyperhydration as well as infusing albumin and fresh frozen plasma may be of particular value for at least the first 4 days after the procedure. PMID- 27385137 TI - The incidence of hoarseness after mediastinoscopy and outcome of video-assisted versus conventional mediastinoscopy in lung cancer staging. AB - Objectives Theoretically, video-assisted mediastinoscopy (VM) should provide a decrease in the incidence of hoarseness in comparison with conventional mediastinoscopy (CM). Methods An investigation of 448 patients with the NSCLC who underwent mediastinoscopy (n = 261 VM, n = 187 CM) between 2006 and 2010. Results With VM, the mean number of sampled LNs and of stations per case were both significantly higher (n = 7.91 +/- 1.97 and n = 4.29 +/- 0.81) than they were for CM (n = 6.65 +/- 1.79 and n = 4.14 +/- 0.84) (p < 0.001 and p = 0.06). Hoarseness was reported in 24 patients (5.4%) with VM procedures resulting in a higher incidence of hoarseness than did CM procedures (6.9% and 3.2%) (p = 0.08). The incidence of hoarseness was observed to be more frequent in patients with left lung carcinoma who had undergone a mediastinoscopy (p = 0.03). Hoarseness developed in 6% of the patients sampled at station 4L, whereas this ratio was 0% in patients who were not sampled at 4L (p = 0.07). A multivariate analysis showed that the presence of a tumor in the left lung is the only independent risk factor indicating hoarseness (p = 0.09). The sensitivity, NPV, and accuracy of VM were calculated as to be 0.87, 0.95, and 0.96, respectively. The same staging values for CM were 0.83, 0.94, and 0.95, respectively. Conclusion VM, the presence of a tumor in the left-lung, and 4L sampling via mediastinoscopy are risk factors for subsequent hoarseness. Probably due to a wider area of dissection, VM can lead to more frequent hoarseness. PMID- 27385138 TI - Malignancy risk of oncocytic changes in thyroid nodules: who should we offer surgery to? AB - Background Oncocytic (Hurthle) cell in fine-needle aspiration biopsy (FNAB) remains challenging for surgeons. Surgical treatment is recommended for oncocytic change in FNAB, since it can sometimes be a struggle to determine the nature of thyroid nodules. We aimed to investigate the clinical significance of oncocytic changes in FNAB in terms of management of patients. Methods The FNAB samples of 172 patients with thyroid nodules were reviewed. Of these, 39 patients with cytologic findings of oncocytic changes on FNAB [POC: predominance of oncocytic cells; SFON-H: suspicious for follicular or oncocytic neoplasm (Hurthle cell type), SM-O: suspicious for malignancy-papillary or follicular carcinoma; oncocytic variant)] were included. Results FNAB demonstrated POC in 14 (35.8%), SFON-H in 15 (38.4%), and SM-O in 10 (25.6%) patients. The overall malignancy rate was 35.8% (n = 14). Clinical and laboratory data were not found to be associated with thyroid cancer while nodule size was significantly higher in patients with thyroid malignancy (15.2 versus 23.3 mm, p = 0.032). Regarding FNAB results including oncocytic changes, the rate of malignancy was significantly different and almost three-fold higher in nodules classified as SFON-H and SM-O [48% versus 14.2% with POC, p = 0.044]. Besides, there was a positive correlation between SFON-H and SM-O cytology and malignancy (p = 0.036, r = 0.337). Conclusions It is hard to discern the significance of oncocytic changes in FNAB report and to determine an optimal approach as a surgeon. We recommend surgery for the patients with an FNAB showing SFON-H and SM-O whereas POC should be better to be followed-up. PMID- 27385139 TI - Outcome of permanent vascular access for haemodialysis in patients with end-stage renal disease in Cameroon: results from the pilot experience of the Douala general hospital. AB - Background Chronic Kidney disease is a major health problem in the world. Native arteriovenous Fistula (AVF) is well established as the best vascular access for haemodialysis. Little is known about the outcome of AVF in sub-Saharan Africa. We aim to analyze the outcome of patients undergoing AVF creation during the pilot program established at the Douala general hospital (DGH). Method This was hospital-based, longitudinal study with a retrospective phase (April 2010-January 2014) and a prospective phase (January 2014-April 2014). All consecutive patients operated for AVF creation were included in this study. Socio-demographics data, functionality, and complications were analyzed. Results Eighty-one patients including 52 men were enrolled in this study (49 prospectively and 32 retrospectively). The mean age was 52, 3 years (range 18-81 years). Hypertension (66, 7%), diabetes (17, 3%), and HIV (8, 6%) were the most observed co morbidities. About 96.3% of AVF were native and 3.7% were prosthetic graft. Radiocephalic AVF was performed at a rate of 77.8%. The primary function rate was 97.7% and the mean follow-up period 43.4 weeks. The overall rate of complications was 44.4% of whom 30.5% were early, 30.5% secondary, and 39% lasted. The treatment of these complications was conservative in 48.7% of cases. Conclusions The results of the pilot program of AVF creation at the DGH are encouraging. However, the sustainability of this project requires human capacity building. PMID- 27385140 TI - Management of a dislocated endovascular aneurysm repair in a challenging giant abdominal aortic aneurysm. AB - Introduction A case report of a contained rupture of an abdominal aneurysm, treated by endovascular technique (EVAR), but complicated by perioperative endoprosthesis limb dislocation. Case report An 81-year old male presented at the emergency department with a contained rupture of an infrarenal aortic aneurysm and bilateral extensive iliac aneurysmatic disease. Open repair was no option, due to the pulmonary condition. The patient was prepped for an emergency EVAR. After placing a bifurcated endoprosthesis, angiography revealed a type IIIa endoleak, due to a dislocation between two left iliac extensions. We converted to a right-sided aorto-uni-iliac endoprosthesis with a femorofemoral bypass. A postoperative CT-scan showed a complete exclusion of the aneurysm, a patent aorto uni-iliac endoprosthesis and a femorofemoral bypass without an endoleak. Discussion EVAR is feasible with a hostile neck AAA, even in a ruptured AAA. In large AAA, one should consider an overlap larger than suggested in the instructions for use. PMID- 27385141 TI - A case of parenchymal-sparing right mainstem bronchial sleeve resection for carcinoid tumor. AB - Introduction Neuroendocrine tumors are rare bronchial carcinomata often presenting in a central airway. Resection usually includes a sleeve of the bronchus with the underlying lobe. Case report We present a 19-year old male with retro-obstructive pneumonia from a tumor in the right mainstem bronchus. Bronchoscopy showed an obstructive mass confirmed as being a typical carcinoid on biopsy. Sleeve resection of the mainstem bronchus only was successfully performed sparing the entire right lung. Discussion and conclusion This type of limited tumoral resection should be reserved for carefully selected patients with a low grade neoplasm without extrabronchial extension and with both tumor-negative lymph nodes and bronchial margins on frozen section. PMID- 27385142 TI - Esophageal wall rupture after EUS-FNA for mediastinal staging: report of two cases. AB - Esophageal wall rupture after EUS-FNA for mediastinal staging is a severe complication. Here we describe the management of two patients with esophageal wall rupture and the presence of empyema. Management was in both cases surgical and consisted of a decortication via thoracotomy. Postoperative IV antibiotics and parenteral nutrition were continued until the first negative X-ray with gastrografin. Both patients recovered and left the hospital in good condition and with oral intake. PMID- 27385143 TI - Intraperitoneal mesh prosthesis metastasis from pancreatic cancer, after laparoscopic hernia repair. AB - Introduction There are very few case reports of metastasis on a mesh prosthesis following laparoscopic hernia repair in the literature and its incidence is completely unknown. Case report A 76-year-old male patient presented in December 2013 with a suspicious malignant lesion of the pancreatic tail on the MRI. He was also complaining of a painful mass in the right para-rectal area. An exploratory laparoscopy performed in December 2013 revealed microscopic whitish peritoneal implants in the left hypochondrium and a massive metastasis involving a mesh prosthesis placed e years before in the right para-rectal area. The pathology report of biopsies of the mesh confirmed a metastasis compatible with a pancreatic tumor. Discussion Possible modes of metastasis and limited published data to date on mesh prosthesis metastasis are presented. This situation can be assimilated to port-site metastasis after laparoscopy. Conclusion A mesh prosthesis metastasis after laparoscopic hernia repair is very rare. PMID- 27385144 TI - Emphysematous cholecystitis due to Clostridium perfringens successfully treated by cholecystectomy. AB - Emphysematous Cholecystitis is life threatening if left untreated. It is associated with arteriosclerosis, embolic events, and diabetes mellitus. In this report, a patient was presented with an early diagnosis of Emphysematous Cholecystitis and was treated by cholecystectomy without complications. A 46-year old male presented at the emergency department. Laboratory results as well as the abdominal ultrasound showed no abnormalities. One day after admission, infection parameters started rising. A computed tomography (CT) showed cholecystitis with a circular gas pattern in bile ducts and gallbladder. After treatment with cholecystectomy and antibiotics, the patient recovered uneventfully. The gallbladder mucosa was denaturized with signs of necrosis. The bile culture was positive for Clostridium perfringens. Treatment was based on preoperative antibiotic treatment combined with cholecystectomy. This resulted in early clinical improvement of the patient and normalization of infection parameters. Therefore, the patient was discharged from the hospital four days postoperatively. PMID- 27385145 TI - Successful surgical repair of a triple cardiac rupture using modified cohesive double patch technique. AB - Introduction The association between both left and right ventricular free wall ruptures (FWR) and post-infarction anterior ventricular septal defect (VSD) is an exceptional situation. Case report We present the case of a patient who developed a VSD and two FWRs (of the left and right ventricle, respectively) shortly after the onset of an anterior AMI. We surgically closed this complex rupture using the cohesive double patch technique with two Teflon patches combined with an infarct exclusion technique. The left and right ventricular patches were attached cohesively to the septal wall and the infarcted area was excluded without reducing the left ventricular cavity. Conclusion Association between post infarction ventricular septal rupture and both left and right free wall ruptures are a very rare and dangerous situation. The modified cohesive double patch technique associated the modified Cooley technique seems to be the correct surgical solution. PMID- 27385146 TI - Andreas vesalius: his surgical activities and influence on modern surgery. PMID- 27385147 TI - Dynamic reconstruction of the spine. PMID- 27385148 TI - Robotic Head and Neck Surgery - The Essential Guide. PMID- 27385149 TI - Sexual complementarity between host humoral toxicity and soldier caste in a polyembryonic wasp. AB - Defense against enemies is a type of natural selection considered fundamentally equivalent between the sexes. In reality, however, whether males and females differ in defense strategy is unknown. Multiparasitism necessarily leads to the problem of defense for a parasite (parasitoid). The polyembryonic parasitic wasp Copidosoma floridanum is famous for its larval soldiers' ability to kill other parasites. This wasp also exhibits sexual differences not only with regard to the competitive ability of the soldier caste but also with regard to host immune enhancement. Female soldiers are more aggressive than male soldiers, and their numbers increase upon invasion of the host by other parasites. In this report, in vivo and in vitro competition assays were used to test whether females have a toxic humoral factor; if so, then its strength was compared with that of males. We found that females have a toxic factor that is much weaker than that of males. Our results imply sexual complementarity between host humoral toxicity and larval soldiers. We discuss how this sexual complementarity guarantees adaptive advantages for both males and females despite the one-sided killing of male reproductives by larval female soldiers in a mixed-sex brood. PMID- 27385150 TI - Facilitators and Barriers for Successful Implementation of Interconception Care in Preventive Child Health Care Services in the Netherlands. AB - Objectives Successful implementation of preconception and interconception care contributes to optimizing pregnancy outcomes. While interconception care to new mothers could potentially be provided by Preventive Child Health Care services, this care is currently not routinely available in the Netherlands. The purpose of this study was to identify facilitators and barriers for implementation of interconception care in Preventive Child Health Care services. Methods We organized four focus groups in which Preventive Child Health Care physicians and nurses, related health care professionals and policymakers participated. A semi structured interview approach was used to guide the discussion. The transcribed discussions were analyzed. Results All four groups agreed that several facilitators are present, such as the unique position to reach women and the expertise in preventive health care. Identified barriers include unfamiliarity with interconception care among patients and health care providers, as well as lack of consensus about the concept of interconception care and how it should be organized. A broad educational campaign, local adaptation, and general agreement or a guideline for standard procedures were recognized as important for future implementation. Conclusions for practice This study identifies potentially important facilitators and barriers for the implementation of interconception care in Preventive Child Health Care services or comparable pediatric settings. These factors should be considered and strategies developed to achieve successful implementation of interconception care. PMID- 27385151 TI - Dextran or Saline Can Replace Contrast for Intravascular Optical Coherence Tomography in Lower Extremity Arteries. AB - PURPOSE: To examine the hypothesis that alternative flush media could be used for lower extremity optical coherence tomography (OCT) imaging in long lesions that would normally require excessive use of contrast. METHODS: The OPTical Imaging Measurement of Intravascular Solution Efficacy (OPTIMISE) trial was a single center, prospective study (ClinicalTrials.gov identifier NCT01743872) that enrolled 23 patients (mean age 68+/-11 years; 14 men) undergoing endovascular intervention involving the superficial femoral artery. Four flush media (heparinized saline, dextran, carbon dioxide, and contrast) were used in succession in random order for each image pullback. Quality was defined as >=270 degrees visualization of vessel wall layers from each axial image. Mean proportions (+/- standard deviation) of image quality for each flush medium were assessed using 1-way analysis of variance and are reported with the 95% confidence intervals (CI). RESULTS: Four OCT catheters failed, leaving 19 patients who completed the OCT imaging protocol; from this cohort, 51 highest quality runs were selected for analysis. Average vessel diameter was 3.99+/-1.01 mm. OCT imaging allowed 10- to 15-MUm resolution of the lumen border, with diminishing quality as vessel diameter increased. Plaque characterization revealed fibrotic lesions. Mean proportions of image quality were dextran 87.2%+/ 12% (95% CI 0.81 to 0.94), heparinized saline 74.3%+/-24.8% (95% CI 0.66 to 0.93), contrast 70.1%+/-30.5% (95% CI 0.52 to 0.88), and carbon dioxide 10.0%+/ 10.4% (95% CI 0.00 to 0.26). Dextran, saline, and contrast provided better quality than carbon dioxide (p<0.001). CONCLUSION: OCT is feasible in peripheral vessels <5 mm in diameter. Dextran or saline flush media can allow lesion characterization, avoiding iodinated contrast. Carbon dioxide is inadequate for peripheral OCT imaging. Axial imaging may aid in enhancing durability of peripheral endovascular interventions. PMID- 27385152 TI - Hemostatic Wound Dressing for Postinterventional Hemostasis in Large Femoral Artery Access Sites: An Initial Efficacy and Safety Study. AB - PURPOSE: To present the results of a prospective single-center study that evaluated the safety and efficacy of a hemostatic dressing following femoral artery access. METHODS: Within a 9-month period, 80 patients (mean age 68+/-14 years; 55 men) were treated with a hemostatic dressing patch (Hematrix Active Patch) containing aminocaproic acid, calcium chloride, and thrombin after endovascular procedures via a 6- to 8-F femoral artery access. After removing the sheath, the wound dressing was placed on the puncture site followed by constant manual compression adapted to the sheath size (specified pressure times: 8 minutes for 6-F, 9 minutes for 7-F, and 10 minutes for 8-F). Patients were treated with an additional pressure bandage for 24 hours. Hemostasis was checked clinically and with duplex ultrasound after patch removal and at 24 hours. Patient characteristics [platelets, systolic blood pressure, international normalized ratio (INR), and partial thromboplastin time (PTT)], sheath sizes, and approach direction were compared among patients with successful hemostasis (within specified pressure times) vs those with prolonged compression. RESULTS: A total of 39 6-F, 19 7-F, and 22 8-F sheaths were employed. In 73 (91.2%) of 80 patients, hemostasis was reached within the prespecified pressure times (mean 8.8+/-0.8 minutes). In 7 patients (4 6-F, 1 7-F, 2 8-F) a longer compression time was necessary (mean 34+/-30 minutes). No serious major complication occurred. Twelve (15.0%) minor and 5 (6.3%) moderate subcutaneous hematomas were observed. Two (2.5%) false aneurysms were treated successfully. Ambulation and discharge was possible within 24 hours in 79 (98.7%) cases. Patients with initial hemostasis and those with prolonged compression did not differ substantially (p>0.05) according to sheath size, approach direction, INR (1.09+/-0.3 vs 1.11+/ 0.3), platelets (234+/-47*10(3)/uL vs 249+/-93*10(3)/uL), systolic blood pressure (150+/-26 vs 152+/-17 mm Hg), or PTT (31+/-7.9 vs 34.8+/-10.0 seconds). CONCLUSION: The evaluated wound dressing seems to be safe and effective in reducing time to hemostasis in large arterial access sites. However, a randomized trial with a larger population and an active control group is necessary to confirm these preliminary data. Moreover, additional focus on shortening the time to ambulation is required in future studies. PMID- 27385154 TI - Sixty-twelve = Seventy-two? A cross-linguistic comparison of children's number transcoding. AB - We compared French- and English-speaking fifth-grade (10-year-old) children's performance in number transcoding. Whereas English two-digit number names follow the decimal structure (base 10), the structure of French two-digit number words over 60 follow a vigesimal structure (base 20). Children undertook two number transcoding tasks. While children were generally successful at the tasks, English speaking children significantly outperformed French-speaking children for numbers following a vigesimal structure in French compared to a decimal structure in English (i.e., numbers >60). Our findings show that verbal number name structures influence children's performance in numerical tasks, even though fifth-grade children have well passed the initial stage of acquiring transcoding skills for two-digit numbers. These findings highlight the importance of language specificities in children's number transcoding. Statement of contribution What is already known? Previous research reports that language influences number processing in young children. Number transcoding performances can be conditioned by the linguistic structure of number words. What does this study add? Our results show how the structure of French vigesimal number words impacts number transcoding. They demonstrate that these language influences also affect children who already master basic number competencies. PMID- 27385153 TI - Challenging Anatomy Predicts Mortality and Complications After Endovascular Treatment of Ruptured Abdominal Aortic Aneurysm. AB - PURPOSE: To analyze the effects of aortic anatomy and endovascular aneurysm repair (EVAR) inside and outside the instructions for use (IFU) on outcomes in patients treated for ruptured abdominal aortic aneurysms (rAAA). METHODS: All 112 patients (mean age 73 years; 102 men) treated with standard EVAR for rAAA between 2000 and 2012 in 3 European centers were included in the retrospective analysis. Patients were grouped based on aortic anatomy and whether EVAR was performed inside or outside the IFU. Data on complications, secondary interventions, and mortality were extracted from the patient records. Cox regression analysis was performed to assess predictors of mortality and complications; results are presented as the hazard ratio (HR) with 95% confidence interval (CI). Survival was analyzed using the Kaplan-Meier method. RESULTS: Of the 112 patients examined, 61 (54%) were treated inside the IFU, 43 (38%) outside the IFU, and 8 patients lacked adequate preoperative computed tomography scans for determination. Median follow-up of those surviving 30 days was 2.5 years. Mortality at 30 days was 15% (95% CI 6% to 24%) inside the IFU vs 30% (95% CI 16% to 45%) outside (p=0.087). Three-year mortality estimates were 33.8% (95% CI 20.0% to 47.5%) inside the IFU vs 56% (95% CI 39.7% to 72.2%) outside (p=0.016). At 5 years, mortality was 48% (95% CI 30% to 66%) inside the IFU vs 74% (95% CI 54% to 93%) outside (p=0.015). Graft-related complications occurred in 6% (95% CI 0% to 13%) inside the IFU and 30% (95% CI 14% to 42%) outside (p=0.015). The rate of graft-related secondary interventions was 14% (95% CI 4% to 22%) inside the IFU vs 35% (95% CI 14% to 42%) outside (p=0.072). In the multivariate analysis, neck length <15 mm (HR 8.1, 95% CI 3.0 to 21.9, p<0.001) and angulation >60 degrees (HR 3.1, 95% CI 1.0 to 9.3, p=0.045) were independent predictors of late graft-related complications. Aneurysm neck diameter >29 mm (HR 2.5, 95% CI 1.1 to 5.9, p=0.035) was an independent predictor of overall mortality. CONCLUSION: Long term mortality and complications after rEVAR are associated with aneurysm anatomy. The role of adjunct endovascular techniques and the outcome of open repair in cases with challenging anatomy warrant further study. PMID- 27385156 TI - Surgery or conservative treatment for rotator cuff tear: a meta-analysis. AB - PURPOSE: Comparative evidence on treating rotator cuff tear is inconclusive. The objective of this review was to evaluate the evidence on effectiveness of tendon repair in reducing pain and improving function of the shoulder when compared with conservative treatment of symptomatic rotator cuff tear. METHOD: Search on CENTRAL, MEDLINE, EMBASE, CINAHL, Web of Science and Pedro databases. Randomised controlled trials (RCT) comparing surgery and conservative treatment of rotator cuff tear. Study selection and extraction based on the Cochrane Handbook for Systematic reviews of Interventions. Random effects meta-analysis. RESULTS: Three identified RCTs involved 252 participants (123 cases and 129 controls). The risk of bias was considered low for all three RCTs. For Constant score, statistically insignificant effect size was 5.6 (95% CI -0.41 to 11.62) points in 1-year follow up favouring surgery and below the level of minimal clinically important difference. The respective difference in pain reduction was -0.93 (95% CI -1.65 to -0.21) cm on a 0-10 pain visual analogue scale favouring surgery. The difference was statistically significant (p = 0.012) in 1-year follow up but below the level of minimal clinically important difference. CONCLUSION: There is limited evidence that surgery is not more effective in treating rotator cuff tear than conservative treatment alone. Thus, a conservative approach is advocated as the initial treatment modality. Implications for Rehabilitation There is limited evidence that surgery is not more effective in treating rotator cuff tear than conservative treatment alone. There was no clinically significant difference between surgery and active physiotherapy in 1-year follow-up in improving Constant score or reducing pain caused by rotator cuff tear. As physiotherapy is less proneness to complications and less expensive than surgery, a conservative approach is advocated as the initial treatment modality to rotator cuff tears. PMID- 27385155 TI - Adjunctive role of MMP-9 inhibition along with conventional anti-tubercular drugs against experimental tuberculous meningitis. AB - Tuberculous meningitis (TBM) is an outcome of neuroinflammatory degeneration caused due to Mycobacterium tuberculosis infection and leads to death or neurological disabilities in the affected individuals. It causes the highest morbidity and mortality amongst all forms of tuberculosis. Matrix metalloproteinase-9 levels increase and cause inflammatory destruction during progression of the disease. Although corticosteroids are usually given as an adjuvant therapy to overcome these complications, treatment outcome is contradictory. This study was designed to evaluate whether specific inhibition of MMP-9 can be beneficial in management of the disease. MMP-9 levels were inhibited using SB-3CT or dexamethasone along with conventional drugs for treatment of tuberculous meningitis. Both SB-3CT and dexamethasone decreased the elevated levels of MMP-9 in sera and tissues of the infected mice. However, dexamethasone administration had an inhibitory effect on bacillary clearance, while SB-3CT potentiated the bacillary clearance, suggesting that MMP-9, if specifically inhibited, can be beneficial in the management of TBM. PMID- 27385158 TI - Nardilysin Is Required for Maintaining Pancreatic beta-Cell Function. AB - Type 2 diabetes (T2D) is associated with pancreatic beta-cell dysfunction, manifested by reduced glucose-stimulated insulin secretion (GSIS). Several transcription factors enriched in beta-cells, such as MafA, control beta-cell function by organizing genes involved in GSIS. Here we demonstrate that nardilysin (N-arginine dibasic convertase; Nrd1 and NRDc) critically regulates beta-cell function through MafA. Nrd1(-/-) mice showed glucose intolerance and severely decreased GSIS. Islets isolated from Nrd1(-/-) mice exhibited reduced insulin content and impaired GSIS in vitro. Moreover, beta-cell-specific NRDc deficient (Nrd1(delbeta)) mice showed a diabetic phenotype with markedly reduced GSIS. MafA was specifically downregulated in islets from Nrd1(delbeta) mice, whereas overexpression of NRDc upregulated MafA and insulin expression in INS832/13 cells. Chromatin immunoprecipitation assay revealed that NRDc is associated with Islet-1 in the enhancer region of MafA, where NRDc controls the recruitment of Islet-1 and MafA transcription. Our findings demonstrate that NRDc controls beta-cell function via regulation of the Islet-1-MafA pathway. PMID- 27385157 TI - Lorcaserin Administration Decreases Activation of Brain Centers in Response to Food Cues and These Emotion- and Salience-Related Changes Correlate With Weight Loss Effects: A 4-Week-Long Randomized, Placebo-Controlled, Double-Blind Clinical Trial. AB - Lorcaserin is a serotonin 5-hydroxytryptamine 2c receptor agonist effective in treating obesity. Studies in rodents have shown that lorcaserin acts in the brain to exert its weight-reducing effects, but this has not yet been studied in humans. We performed a randomized, placebo-controlled, double-blind trial with 48 obese participants and used functional MRI to study the effects of lorcaserin on the brain. Subjects taking lorcaserin had decreased brain activations in the attention-related parietal and visual cortices in response to highly palatable food cues at 1 week in the fasting state and in the parietal cortex in response to any food cues at 4 weeks in the fed state. Decreases in emotion- and salience related limbic activity, including the insula and amygdala, were attenuated at 4 weeks. Decreases in caloric intake, weight, and BMI correlated with activations in the amygdala, parietal, and visual cortices at baseline. These data suggest that lorcaserin exerts its weight-reducing effects by decreasing attention related brain activations to food cues (parietal and visual cortices) and emotional and limbic activity (insula, amygdala). Results indicating that baseline activation of the amygdala relates to increased efficacy suggest that lorcaserin would be of particular benefit to emotional eaters. PMID- 27385160 TI - Clinical and Echocardiographic Characteristics of Acute Cardiac Dysfunction Associated With Acute Brain Hemorrhage - Difference From Takotsubo Cardiomyopathy. AB - BACKGROUND: Cardiac dysfunction (CD) associated with brain hemorrhage is similar to that with takotsubo cardiomyopathy but still not well understood. We aimed to investigate the clinical and echocardiographic findings of acute CD (ACD) related to brain hemorrhage. METHODS AND RESULTS: Between 2013 and 2014, consecutive patients diagnosed with spontaneous and traumatic brain hemorrhage were prospectively enrolled. Electrocardiography, cardiac enzymes, and echocardiography were performed. Left ventricular (LV) systolic dysfunction on echocardiography was defined as ACD related to brain hemorrhage when all the following conditions were satisfied: abnormal ECG and cardiac troponin level, LV wall motion abnormality or decreased LV systolic function on echocardiography, and no previous history of cardiac disease. Otherwise, LV dysfunction was considered to be other CD unrelated to brain hemorrhage. In a total of 208 patients, 15 (7.2%) showed ACD. Of them, 8 patients were men and 8 showed apex sparing LV hypokinesia and 9 died in hospital. Other cardiac abnormalities observed in the study patients were NT-proBNP elevation (n=123), QT interval prolongation (n=95), LV hypertrophy (n=89), and troponin I elevation (n=47). There were 36 in-hospital deaths (17.3%). Glasgow coma score and ACD were independently associated with in-hospital death. CONCLUSIONS: ACD was observed in patients with various brain hemorrhages. Unlike takotsubo cardiomyopathy, high proportions of male sex, apex-sparing LV dysfunction, and in-hospital death were observed for ACD associated with brain hemorrhage. (Circ J 2016; 80: 2026-2032). PMID- 27385159 TI - Inhibition of Pyruvate Dehydrogenase Kinase 2 Protects Against Hepatic Steatosis Through Modulation of Tricarboxylic Acid Cycle Anaplerosis and Ketogenesis. AB - Hepatic steatosis is associated with increased insulin resistance and tricarboxylic acid (TCA) cycle flux, but decreased ketogenesis and pyruvate dehydrogenase complex (PDC) flux. This study examined whether hepatic PDC activation by inhibition of pyruvate dehydrogenase kinase 2 (PDK2) ameliorates these metabolic abnormalities. Wild-type mice fed a high-fat diet exhibited hepatic steatosis, insulin resistance, and increased levels of pyruvate, TCA cycle intermediates, and malonyl-CoA but reduced ketogenesis and PDC activity due to PDK2 induction. Hepatic PDC activation by PDK2 inhibition attenuated hepatic steatosis, improved hepatic insulin sensitivity, reduced hepatic glucose production, increased capacity for beta-oxidation and ketogenesis, and decreased the capacity for lipogenesis. These results were attributed to altered enzymatic capacities and a reduction in TCA anaplerosis that limited the availability of oxaloacetate for the TCA cycle, which promoted ketogenesis. The current study reports that increasing hepatic PDC activity by inhibition of PDK2 ameliorates hepatic steatosis and insulin sensitivity by regulating TCA cycle anaplerosis and ketogenesis. The findings suggest PDK2 is a potential therapeutic target for nonalcoholic fatty liver disease. PMID- 27385161 TI - An Ideal Time to Solve a Clinical Dilemma in the Golden Age of Aortic Stenosis Therapy. PMID- 27385163 TI - Mindful attention predicts greater recovery from negative emotions, but not reduced reactivity. AB - This study investigated the role of dispositional mindful attention in immediate reactivity to, and subsequent recovery from, laboratory-induced negative emotion. One hundred and fourteen undergraduates viewed blocks of negative pictures followed by neutral pictures. Participants' emotional responses to negative pictures and subsequent neutral pictures were assessed via self-reported ratings. Participants' emotional response to negative pictures was used to index level of emotional reactivity to unpleasant stimuli; emotional response to neutral pictures presented immediately after the negative pictures was used to index level of emotional recovery from pre-induced negative emotion (residual negativity). Results indicated that mindful attention was not associated with the emotional response to negative pictures, but it was associated with reduced negative emotion in response to the neutral pictures presented immediately after the negative pictures, suggesting better recovery as opposed to reduced reactivity. This effect was especially pronounced in later experimental blocks when the accumulation of negative stimuli produced greater negative emotion from which participants had to recover. The current study extends previous findings on the relationship between dispositional mindfulness and reduced negative emotion by demonstrating that mindful attention may facilitate better recovery from negative emotion, possibly through more effective disengagement from previous stimuli. PMID- 27385162 TI - In Vivo MRI and X-Ray Bifunctional Imaging of Polymeric Composite Supplemented with GdPO4 .H2 O Nanobundles for Tracing Bone Implant and Bone Regeneration. AB - Homogeneous and monodisperse GdPO4 .H2 O nanobundles are successfully synthesized via a solvothermal method. Then, GdPO4 .H2 O are incorporated into the composite of hydroxyapatite and poly(lactic-co-glycolic acid) to obtain a biodegradable and traceable bone implant. After implanted, the GdPO4 .H2 O/HA/PLGA implant and the newly formed bone can be easily traced and observed through the combination of magnetic resonance imaging and X-ray imaging. PMID- 27385164 TI - Inverse scattering transform analysis of rogue waves using local periodization procedure. AB - The nonlinear Schrodinger equation (NLSE) stands out as the dispersive nonlinear partial differential equation that plays a prominent role in the modeling and understanding of the wave phenomena relevant to many fields of nonlinear physics. The question of random input problems in the one-dimensional and integrable NLSE enters within the framework of integrable turbulence, and the specific question of the formation of rogue waves (RWs) has been recently extensively studied in this context. The determination of exact analytic solutions of the focusing 1D NLSE prototyping RW events of statistical relevance is now considered as the problem of central importance. Here we address this question from the perspective of the inverse scattering transform (IST) method that relies on the integrable nature of the wave equation. We develop a conceptually new approach to the RW classification in which appropriate, locally coherent structures are specifically isolated from a globally incoherent wave train to be subsequently analyzed by implementing a numerical IST procedure relying on a spatial periodization of the object under consideration. Using this approach we extend the existing classifications of the prototypes of RWs from standard breathers and their collisions to more general nonlinear modes characterized by their nonlinear spectra. PMID- 27385165 TI - Biogeochemical Controls of Uranium Bioavailability from the Dissolved Phase in Natural Freshwaters. AB - To gain insights into the risks associated with uranium (U) mining and processing, we investigated the biogeochemical controls of U bioavailability in the model freshwater species Lymnaea stagnalis (Gastropoda). Bioavailability of dissolved U(VI) was characterized in controlled laboratory experiments over a range of water hardness, pH, and in the presence of complexing ligands in the form of dissolved natural organic matter (DOM). Results show that dissolved U is bioavailable under all the geochemical conditions tested. Uranium uptake rates follow first order kinetics over a range encompassing most environmental concentrations. Uranium uptake rates in L. stagnalis ultimately demonstrate saturation uptake kinetics when exposure concentrations exceed 100 nM, suggesting uptake via a finite number of carriers or ion channels. The lack of a relationship between U uptake rate constants and Ca uptake rates suggest that U does not exclusively use Ca membrane transporters. In general, U bioavailability decreases with increasing pH, increasing Ca and Mg concentrations, and when DOM is present. Competing ions did not affect U uptake rates. Speciation modeling that includes formation constants for U ternary complexes reveals that the aqueous concentration of dicarbonato U species (UO2(CO3)2(-2)) best predicts U bioavailability to L. stagnalis, challenging the free-ion activity model postulate. PMID- 27385166 TI - The Rise and Fall in Out-of-Pocket Costs in Australia: An Analysis of the Strengthening Medicare Reforms. AB - After a period of steady decline, out-of-pocket (OOP) costs for general practitioner (GP) consultations in Australia began increasing in the mid-1990s. Following the rising community concerns about the increasing costs, the Australian Government introduced the Strengthening Medicare reforms in 2004 and 2005, which included a targeted incentive for GPs to charge zero OOP costs for consultations provided to children and concession cardholders (older adults and the poor), as well as an increase in the reimbursement for all GP visits. This paper examines the impact of those reforms using longitudinal survey and administrative data from a large national sample of women. The findings suggest that the reforms were effective in reducing OOP costs by an average of $A0.40 per visit. Decreases in OOP costs, however, were not evenly distributed. Those with higher pre-reform OOP costs had the biggest reductions in OOP costs, as did those with concession cards. However, results also reveal increases in OOP costs for most people without a concession card. The analysis suggests that there has been considerable heterogeneity in GP responses to the reforms, which has led to substantial changes in the fees charged by doctors and, as a result, the OOP costs incurred by different population groups. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27385167 TI - Standardizing Biparametric MRI to Simplify and Improve Prostate Imaging Reporting and Data System, Version 2, in Prostate Cancer Management. PMID- 27385168 TI - Role of Hepatic Drug Transporters in Drug Development. AB - Hepatic drug transporters can play an important role in pharmacokinetics and the disposition of therapeutic drugs and endogenous substances. Altered function of hepatic drug transporters due to drug-drug interactions (DDIs), genetic polymorphisms, and disease states can often result in a change in systemic and/or tissue exposure and subsequent pharmacological/toxicological effects of their substrates. Regulatory agencies including the US Food and Drug Administration, European Medicines Agency, and Japan Pharmaceuticals and Medical Devices Agency have issued guidance for industry on drug interaction studies, which contain comprehensive recommendations on in vitro and in vivo study tools and cutoff values to evaluate the DDI potential of new molecular entities mediated by hepatic drug transporters. In this report we summarize the latest regulatory and scientific progress of hepatic drug transporters in clinical DDIs, pharmacogenetics, drug-induced liver injury (DILI), as well as methods for predicting transporter-mediated pharmacokinetics and DDIs. PMID- 27385169 TI - Evaluation and Quantitative Prediction of Renal Transporter-Mediated Drug-Drug Interactions. AB - With numerous drugs cleared renally, inhibition of uptake transporters localized on the basolateral membrane of renal proximal tubule cells, eg, organic anion transporters (OATs) and organic cation transporters (OCTs), may lead to clinically meaningful drug-drug interactions (DDIs). Additionally, clinical evidence for the possible involvement of efflux transporters, such as P glycoprotein (P-gp) and multidrug and toxin extrusion protein 1/2-K (MATE1/2-K), in the renal DDIs is emerging. Herein, we review recent progress regarding mechanistic understanding of transporter-mediated renal DDIs as well as the quantitative predictability of renal DDIs using static and physiologically based pharmacokinetic (PBPK) models. Generally, clinical DDI data suggest that the magnitude of plasma exposure changes attributable to renal DDIs is less than 2 fold, unlike the DDIs associated with inhibition of cytochrome P-450s and/or hepatic uptake transporters. It is concluded that although there is a need for risk assessment early in drug development, current available data imply that safety concerns related to the renal DDIs are generally low. Nevertheless, consideration must be given to the therapeutic index of the victim drug and potential risk in a specific patient population (eg, renal impairment). Finally, in vitro transporter data and clinical pharmacokinetic parameters obtained from the first-in-human studies have proven useful in support of quantitative prediction of DDIs associated with inhibition of renal secretory transporters, OATs or OCTs. PMID- 27385170 TI - The Application of Physiologically Based Pharmacokinetic Modeling to Predict the Role of Drug Transporters: Scientific and Regulatory Perspectives. AB - Transporters play an important role in drug absorption, disposition, and drug action. The evaluation of drug transporters requires a comprehensive understanding of transporter biology and pharmacology. Physiologically based pharmacokinetic (PBPK) models may offer an integrative platform to quantitatively evaluate the role of drug transporters and its interplay with other drug disposition processes such as passive drug diffusion and elimination by metabolizing enzymes. To date, PBPK modeling and simulations integrating drug transporters lag behind that for drug-metabolizing enzymes. In addition, predictive performance of PBPK has not been well established for predicting the role of drug transporters in the pharmacokinetics of a drug. To enhance overall predictive performance of transporter-based PBPK models, it is necessary to have a detailed understanding of transporter biology for proper representation in the models and to have a quantitative understanding of the contribution of transporters in the absorption and metabolism of a drug. This article summarizes PBPK-based submissions evaluating the role of drug transporters to the Office of Clinical Pharmacology of the US Food and Drug Administration. PMID- 27385172 TI - Use of PET Imaging to Evaluate Transporter-Mediated Drug-Drug Interactions. AB - Several membrane transporters belonging to the adenosine triphosphate-binding cassette (ABC) and solute carrier (SLC) families can transport drugs and drug metabolites and thereby exert an effect on drug absorption, distribution, and excretion, which may potentially lead to transporter-mediated drug-drug interactions (DDIs). Some transporter-mediated DDIs may lead to changes in organ distribution of drugs (eg, brain, liver, kidneys) without affecting plasma concentrations. Positron emission tomography (PET) is a noninvasive imaging method that allows studying of the distribution of radiolabeled drugs to different organs and tissues and is therefore the method of choice to quantitatively assess transporter-mediated DDIs on a tissue level. There are 2 approaches to how PET can be used in transporter-mediated DDI studies. When the drug of interest is a potential perpetrator of DDIs, it may be administered in unlabeled form to assess its influence on tissue distribution of a generic transporter-specific PET tracer (probe substrate). When the drug of interest is a potential victim of DDIs, it may be radiolabeled with carbon-11 or fluorine-18 and used in combination with a prototypical transporter inhibitor (eg, rifampicin). PET has already been used both in preclinical species and in humans to assess the effects of transporter-mediated DDIs on drug disposition in different organ systems, such as brain, liver, and kidneys, for which examples are given in the present review article. Given the growing importance of membrane transporters with respect to drug safety and efficacy, PET is expected to play an increasingly important role in future drug development. PMID- 27385171 TI - More Power to OATP1B1: An Evaluation of Sample Size in Pharmacogenetic Studies Using a Rosuvastatin PBPK Model for Intestinal, Hepatic, and Renal Transporter Mediated Clearances. AB - Rosuvastatin is a substrate of choice in clinical studies of organic anion transporting polypeptide (OATP)1B1- and OATP1B3-associated drug interactions; thus, understanding the effect of OATP1B1 polymorphisms on the pharmacokinetics of rosuvastatin is crucial. Here, physiologically based pharmacokinetic (PBPK) modeling was coupled with a power calculation algorithm to evaluate the influence of sample size on the ability to detect an effect (80% power) of OATP1B1 phenotype on pharmacokinetics of rosuvastatin. Intestinal, hepatic, and renal transporters were mechanistically incorporated into a rosuvastatin PBPK model using permeability-limited models for intestine, liver, and kidney, respectively, nested within a full PBPK model. Simulated plasma rosuvastatin concentrations in healthy volunteers were in agreement with previously reported clinical data. Power calculations were used to determine the influence of sample size on study power while accounting for OATP1B1 haplotype frequency and abundance in addition to its correlation with OATP1B3 abundance. It was determined that 10 poor transporter and 45 intermediate-transporter individuals are required to achieve 80% power to discriminate the AUC0-48h of rosuvastatin from that of the extensive transporter phenotype. This number was reduced to 7 poor-transporter and 40 intermediate-transporter individuals when the reported correlation between OATP1B1 and 1B3 abundance was taken into account. The current study represents the first example in which PBPK modeling in conjunction with power analysis has been used to investigate sample size in clinical studies of OATP1B1 polymorphisms. This approach highlights the influence of interindividual variability and correlation of transporter abundance on study power and should allow more informed decision making in pharmacogenomic study design. PMID- 27385173 TI - The Role of Transporters in the Toxicity of Chemotherapeutic Drugs: Focus on Transporters for Organic Cations. AB - The introduction of chemotherapy in the treatment of cancer is one of the most important achievements of modern medicine, even allowing the cure of some lethal diseases such as testicular cancer and other malignant neoplasms. The number and type of chemotherapeutic agents available have steadily increased and have developed until the introduction of targeted tumor therapy. It is now evident that transporters play an important role for determining toxicity of chemotherapeutic drugs not only against target but also against nontarget cells. This is of special importance for intracellularly active hydrophilic drugs, which cannot freely penetrate the plasma membrane. Because many important chemotherapeutic agents are substrates of transporters for organic cations, this review discusses the known interaction of these substances with these transporters. A particular focus is given to the role of transporters for organic cations in the development of side effects of chemotherapy with platinum derivatives and in the efficacy of recently developed tyrosine kinase inhibitors to specifically target cancer cells. It is evident that specific inhibition of uptake transporters may be a possible strategy to protect against undesired side effects of platinum derivatives without compromising their antitumor efficacy. These transporters are also important for efficient targeting of tyrosine kinase inhibitors to cancer cells. However, in order to achieve the aims of protecting from undesired toxicities and improving the specificity of uptake by tumor cells, an exact knowledge of transporter expression, function, regulation under normal and pathologic conditions, and of genetically and epigenetically regulation is mandatory. PMID- 27385174 TI - Causes and Consequences of Variability in Drug Transporter Activity in Pediatric Drug Therapy. AB - Drug transporters play a key role in mediating the uptake of endo- and exogenous substances into cells as well as their efflux. Therefore, variability in drug transporter activity can influence pharmaco- and toxicokinetics and be a determinant of drug safety and efficacy. In children, particularly in neonates and young infants, the contribution of tissue-specific drug transporters to drug absorption, distribution, and excretion may differ from that in adults. In this review 5 major factors and their interdependence that may influence drug transporter activity in children are discussed: developmental differences, genetic polymorphisms, pediatric comorbidities, interacting comedication, and environmental factors. Even if data are sparse, altered drug transporter activity due to those factors have been associated with clinically relevant differences in drug disposition, efficacy, and safety in pediatric patients. Single nucleotide polymorphisms in drug transporter-encoding genes were the most studied source of drug transporter variability in children. However, in the age group where drug transporter activity has been reported to differ from that in adults, namely neonates and young infants, hardly any studies have been performed. Longitudinal studies in this young population are required to investigate the age- and disease dependent genotype-phenotype relationships and relevance of drug transporter drug drug interactions. Physiologically based pharmacokinetic modeling approaches can integrate drug- and patient-specific parameters, including drug transporter ontogeny, and may further improve in silico predictions of pediatric-specific pharmacokinetics. PMID- 27385175 TI - Review of Transporter-Related Postmarketing Requirement or Postmarketing Commitment Studies. AB - The objectives of this report are to summarize the content and status of transporter-related postmarketing requirement (PMR)/postmarketing commitment (PMC) studies in new drug applications (NDAs) approved by the U.S. Food and Drug Administration (FDA) and to discuss the reasons for requesting such studies and the impact of PMR/PMC study results on labeling to guide the optimal use of the drugs. Multiple data sources were searched to collect information on transporter related PMR/PMC studies between January 1999 and May 2015. A total of 40 transporter-related PMR/PMC study requests were issued for 35 NDAs. Among these PMR/PMC studies, 27 requested studies related to P-glycoprotein. As of May 31, 2015, 34 transporter-related PMR/PMC studies (85%) are considered "fulfilled" (per the FDA's PMR/PMC website), and 22 (65%) resulted in labeling updates. The majority of the PMR/PMC studies are for drugs in the therapeutic areas of anti infectives, oncology, and neurology. The results from PMR/PMC studies are important for dosing optimization and are often included in the updated labeling. Because a significant lag time is anticipated between drug approval and PMR/PMC fulfillment, NDA applicants are encouraged to include transporter-related assessments in clinical drug development programs for drug products. PMID- 27385176 TI - Effect of Disease Pathologies on Transporter Expression and Function. AB - Transporters are important determinants of drug absorption, distribution, and excretion. The clinical relevance of drug transporters in drug disposition and toxicology depends on their localization in liver, kidney, and brain. There has been growing evidence regarding the importance of disease status on alterations in metabolizing enzymes and transporter proteins. This review focuses on uptake and efflux transporter proteins in liver, kidney, and brain and discusses mechanisms of altered transporter expression and function secondary to disease. PMID- 27385178 TI - Impact of Transporter Polymorphisms on Drug Development: Is It Clinically Significant? AB - Drug transporters are becoming increasingly recognized as relevant to the drug development process. This may be a reflection of increasing target complexity and the need for high-affinity interaction with drug targets that minimize off-target side effects. Moreover, as new molecular entities (NMEs) become larger in size and amphipathic in nature, interaction with drug transporters, both uptake as well as efflux, becomes increasingly likely. In some cases transporters may limit the absorption or organ-specific entry of NMEs, whereas in other cases transporters may enhance their absorption or tissue accumulation. Indeed, in some cases, transporters may prove to be a therapeutic target. Accordingly, a better understanding of potentially clinically relevant drug transporter polymorphisms earlier in the drug development process is highly desirable. In this review we examine key transporters that are important to the absorption, distribution, and excretion of a large number of drugs in clinical use. Importantly, we provide our assessment of the potential impact of known polymorphisms in such transporters and discuss whether there is sufficient evidence to incorporate these polymorphisms in the drug development process. PMID- 27385177 TI - Importance of Hepatic Transporters in Clinical Disposition of Drugs and Their Metabolites. AB - This review provides a practical clinical perspective on the relevance of hepatic transporters in pharmacokinetics and drug-drug interactions (DDIs). Special emphasis is placed on transporters with clear relevance to clinical DDIs, efficacy, and safety. Basolateral OATP1B1 and 1B3 emerged as important hepatic drug uptake pathways, sites for systemic DDIs, and sources of pharmacogenetic variability. As the first step in hepatic drug removal from the circulation, OATPs are an important determinant of systemic pharmacokinetics, specifically influencing systemic absorption, clearance, and hepatic distribution for subsequent metabolism and/or excretion. Biliary excretion of parent drugs is a less prevalent clearance pathway than metabolism or urinary excretion, but BCRP and MRP2 are critically important to biliary/fecal elimination of drug metabolites. Inhibition of biliary excretion is typically not apparent at the level of systemic pharmacokinetics but can markedly increase liver exposure. Basolateral efflux transporters MRP3 and MRP4 mediate excretion of parent drugs and, more commonly, polar metabolites from hepatocytes into blood. Basolateral excretion is an area in need of further clinical investigation, which will necessitate studies more complex than just systemic pharmacokinetics. Clinical relevance of hepatic uptake is relatively well appreciated, and clinical consequences of hepatic excretion (biliary and basolateral) modulation remain an active research area. PMID- 27385179 TI - Comparing Various In Vitro Prediction Criteria to Assess the Potential of a New Molecular Entity to Inhibit Organic Anion Transporting Polypeptide 1B1. AB - Evaluation of organic anion transporting polypeptide (OATP) 1B1-mediated drug drug interactions (DDIs) is an integral part of drug development and is recommended by regulatory agencies. In this study we compared various prediction methods and cutoff criteria based on in vitro inhibition data to assess the potential of a new molecular entity to inhibit OATP1B1 in vivo. In vitro (eg, IC50 , fu,p ) and in vivo (eg, dose, Cmax , change in area under the curve [AUC]) data for 11 substrates and 61 inhibitors for OATP1B1 were obtained from literature and Drugs@FDA, which include 107 clinical (in vivo) DDI studies. Substrate dependency and variability of IC50 values were noted. In addition to the ratio of unbound or total systemic concentration (Imax,u and Imax ) to IC50 , maximum unbound inhibitor concentration at the inlet to the liver (Iu,in,max ) was used for the estimation of "R value" where R = 1 + Iu,in,max /IC50 . Based on our analyses, Imax /Ki >= 0.1, R >= 1.04, or R >= 1.1 seem to be appropriate for reducing the false-negative (FN) predictions. However, as compared with R >= 1.1, Imax /Ki >= 0.1 and R >= 1.04 resulted in higher false positives (FPs) and lower true negatives (TNs). R >= 1.1, Imax,u /Ki >= 0.02, and R >= 1.25 alone, or combined criterion of Imax /Ki >= 0.1 and R >= 1.25, were reasonable to determine the need to perform clinical DDI studies with OATP1B1 substrates with similar positive and negative predictive values. Possible reasons of FP or FN from different decision criteria should be considered when interpreting prediction results, and the variability in IC50 determination needs to be understood and minimized. PMID- 27385180 TI - Role of Transporters in Drug Development. PMID- 27385181 TI - Renal Transporter-Mediated Drug-Drug Interactions: Are They Clinically Relevant? AB - The kidney, through the distinct processes of passive glomerular filtration and active tubular secretion, plays an important role in the elimination of numerous endobiotics (eg, hormones, metabolites), toxins, nutrients, and drugs. Renal transport pathways mediating active tubular secretion and reabsorption in the proximal tubule are complex, involving apical and basolateral transporters acting in concert. Detailed studies of the molecular mechanisms of net active tubular secretion have established the involvement of multiple transporters with overlapping substrate specificity mediating competing secretion and reabsorption pathways. Although drug interactions arising from inhibition of renal transporters are rare relative to other mechanisms, they can involve commonly administered drugs (eg, cimetidine, metformin), may be underappreciated due to muted effects on plasma pharmacokinetics relative to tissue levels, can affect narrow-therapeutic-index medications (eg, antiarrhythmic, oncology medications), and may disproportionately affect sensitive populations where polypharmacy is common (eg, the elderly, diabetics). In particular, there is the potential for larger-magnitude interactions in subjects with reduced glomerular filtration rates due to the increased relative contribution of tubular secretion. The assessment of additional endpoints in drug-drug interaction studies including pharmacodynamics, positron emission tomography imaging, and metabolomics promises to expand our understanding of the clinical relevance of renal drug interactions. PMID- 27385182 TI - Evaluation of Proposed In Vivo Probe Substrates and Inhibitors for Phenotyping Transporter Activity in Humans. AB - Drug transporters are present in various tissues and have a significant role in drug absorption, distribution, and elimination. The International Transporter Consortium has identified 7 transporters of increasing importance from evidence of clinically significant transporter-mediated drug-drug interactions. The transporters are P-glycoprotein, breast cancer resistance protein, organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic cation transporter 2, organic anion transporters (OAT) 1, and OAT3. Decision trees were created based on in vitro experiments to determine whether an in vivo transporter-mediated drug drug interaction study is needed. Phenotyping is a methodology that evaluates real-time in vivo transporter activity, whereby changes in a probe substrate or probe inhibitor reflect alternations in the activity of the specified transporter. In vivo probe substrates and/or probe inhibitors have been proposed for each aforementioned transporter. In vitro findings and animal models provide the strongest evidence regarding probe specificity. However, such findings have not conclusively correlated with human phenotyping studies. Furthermore, the extent of contribution from multiple transporters in probe disposition complicates the ability to discern if study findings are the result of a specific transporter and thus provide a recommendation for a preferred probe for a drug transporter. PMID- 27385183 TI - Transporter-Enzyme Interplay: Deconvoluting Effects of Hepatic Transporters and Enzymes on Drug Disposition Using Static and Dynamic Mechanistic Models. AB - A large body of evidence suggests hepatic uptake transporters, organic anion transporting polypeptides (OATPs), are of high clinical relevance in determining the pharmacokinetics of substrate drugs, based on which recent regulatory guidances to industry recommend appropriate assessment of investigational drugs for the potential drug interactions. We recently proposed an extended clearance classification system (ECCS) framework in which the systemic clearance of class 1B and 3B drugs is likely determined by hepatic uptake. The ECCS framework therefore predicts the possibility of drug-drug interactions (DDIs) involving OATPs and the effects of genetic variants of SLCO1B1 early in the discovery and facilitates decision making in the candidate selection and progression. Although OATP-mediated uptake is often the rate-determining process in the hepatic clearance of substrate drugs, metabolic and/or biliary components also contribute to the overall hepatic disposition and, more importantly, to liver exposure. Clinical evidence suggests that alteration in biliary efflux transport or metabolic enzymes associated with genetic polymorphism leads to change in the pharmacodynamic response of statins, for which the pharmacological target resides in the liver. Perpetrator drugs may show inhibitory and/or induction effects on transporters and enzymes simultaneously. It is therefore important to adopt models that frame these multiple processes in a mechanistic sense for quantitative DDI predictions and to deconvolute the effects of individual processes on the plasma and hepatic exposure. In vitro data-informed mechanistic static and physiologically based pharmacokinetic models are proven useful in rationalizing and predicting transporter-mediated DDIs and the complex DDIs involving transporter-enzyme interplay. PMID- 27385184 TI - Optimal Perceived Timing: Integrating Sensory Information with Dynamically Updated Expectations. AB - The environment has a temporal structure, and knowing when a stimulus will appear translates into increased perceptual performance. Here we investigated how the human brain exploits temporal regularity in stimulus sequences for perception. We find that the timing of stimuli that occasionally deviate from a regularly paced sequence is perceptually distorted. Stimuli presented earlier than expected are perceptually delayed, whereas stimuli presented on time and later than expected are perceptually accelerated. This result suggests that the brain regularizes slightly deviant stimuli with an asymmetry that leads to the perceptual acceleration of expected stimuli. We present a Bayesian model for the combination of dynamically-updated expectations, in the form of a priori probability of encountering future stimuli, with incoming sensory information. The asymmetries in the results are accounted for by the asymmetries in the distributions involved in the computational process. PMID- 27385185 TI - Antiatherogenic Roles of Dietary Flavonoids Chrysin, Quercetin, and Luteolin. AB - Cardiovascular diseases (CVDs) are the commonest cause of global mortality and morbidity. Atherosclerosis, the fundamental pathological manifestation of CVDs, is a complex process and is poorly managed both in terms of preventive and therapeutic intervention. Aberrant lipid metabolism and chronic inflammation play critical roles in the development of atherosclerosis. These processes can be targeted for effective management of the disease. Although managing lipid metabolism is in the forefront of current therapeutic approaches, controlling inflammation may also prove to be crucial for an efficient treatment regimen of the disease. Flavonoids, the plant-derived polyphenols, are known for their antiinflammatory properties. This review discusses the possible antiatherogenic role of 3 flavonoids, namely, chrysin, quercetin, and luteolin primarily known for their antiinflammatory properties. PMID- 27385186 TI - Morphological Identification of TRPC7 in Cardiomyocytes from Normal and Renovascular Hypertensive Rats: Retraction. PMID- 27385188 TI - The Role of Ate Complexes in the Copper-Mediated Trifluoromethylation of Alkynes. AB - Trifluoromethylation reactions have recently received increased attention because of the beneficial effect of the trifluoromethyl group on the pharmacological properties of numerous substances. A common method to introduce the trifluoromethyl group employs the Ruppert-Prakash reagent, that is, Si(CH3 )3 CF3 , together with a copper(I) halide. We have applied this method to the trifluoromethylation of aromatic alkynes and used electrospray-ionization mass spectrometry to investigate the mechanism of these reactions in tetrahydrofuran, dichloromethane, and acetonitrile as well as with and without added 1,10 phenanthroline. In the absence of the alkyne component, the homoleptic ate complexes [Cu(CF3 )2 ](-) and [Cu(CF3 )4 ](-) were observed. In the presence of the alkynes RH, the heteroleptic complexes [Cu(CF3 )3 R](-) were detected as well. Upon gas-phase fragmentation, these key intermediates released the cross coupling products R-CF3 with perfect selectivity. Apparently, the [Cu(CF3 )3 R]( ) complexes did not originate from homoleptic cuprate anions, but from unobservable neutral precursors. The present results moreover point to the involvement of oxygen as the oxidizing agent. PMID- 27385187 TI - Prenatal PBDE and PCB Exposures and Reading, Cognition, and Externalizing Behavior in Children. AB - BACKGROUND: Prenatal polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) exposures may influence children's neurodevelopment. OBJECTIVE: We examined the association of prenatal PBDE and PCB exposures with children's reading skills at ages 5 and 8 years, Full-Scale Intelligence Quotient (FSIQ), and externalizing behavior problems at age 8 years. METHODS: From 239 mother child pairs recruited (2003-2006) in Cincinnati, Ohio, we measured maternal serum PBDE and PCB concentrations, assessed child's reading skills using the Woodcock Johnson Tests of Achievement III (WJ-III) at age 5 years and the Wide Range Achievement Test-4 (WRAT-4) at age 8 years, tested FSIQ using the Wechsler Intelligence Scale for Children-IV (WISC-IV), and externalizing behavior problems using the Behavioral Assessment System for Children-2 (BASC-2) at age 8 years. We used multiple linear regression to examine the association of prenatal PBDE and PCB concentrations and reading, FSIQ, and externalizing behavior problems after adjusting for covariates. RESULTS: An increase of Sum4PBDEs (BDE-47, BDE-99, BDE 100, and BDE-153) by 10 times was not significantly associated with reading scores at age 5 years at the p = 0.05 level but was inversely associated with Reading Composite scores (beta: -6.2, 95% CI: -11.7, -0.6) and FSIQ (beta: -5.3, 95% CI: -10.6, -0.02) at age 8 years; it was positively associated with the score for externalizing behavior problems (beta: 3.5, 95% CI: -0.1, 7.2) at age 8 years. Prenatal Sum4PCBs (PCB-118, -153, -138-158, and -180) was not significantly associated with a child's reading skills, FSIQ, and externalizing behavior problems. CONCLUSION: Prenatal PBDE concentration was inversely associated with reading skills and FSIQ and positively associated with externalizing behavior problems at age 8 years. No significant associations were found in prenatal PCB concentration. PMID- 27385189 TI - Sunscreen Product Performance and Other Determinants of Consumer Preferences. AB - IMPORTANCE: Sunscreen use is a modifiable behavior that can help reduce the risk for skin cancer, prevent sunburns, mitigate photoaging, and treat photosensitive dermatoses. A better understanding of consumer sunscreen preferences would inform dermatologists in their own recommendations. OBJECTIVE: To determine the characteristics and the most commonly cited positive and negative features of highly rated sunscreens described by consumers. DESIGN, SETTING, AND PARTICIPANTS: The top 1 percentile of sunscreen products on Amazon.com as of December 2015 was selected according to average consumer review (>=4 stars) and the highest number of consumer reviews. Descriptive data for each product were collected from the product page and manufacturer claims. The top 5 "most helpful" reviews (positive and critical) were analyzed and coded by a consensus qualitative coding scheme, which included positive and negative descriptors in 6 major categories according to consumer comments: affordability, cosmetic elegance, separate ratings, product ingredients, product performance, and skin compatibility. MAIN OUTCOMES AND MEASURES: The Kruskal-Wallis test was performed to determine whether characteristics of each product (eg, American Academy of Dermatology [AAD] criteria, sun protection factor [SPF], or vehicle) could be used to predict price per ounce. The number (percentage) of comments categorized by major themes and subthemes was determined. Illustrative consumer comments were also collected. RESULTS: There were 6500 products categorized as sunscreens in the Amazon.com, online catalog. Of the 65 products evaluated, the median price per ounce was $3.32 (range, $0.68-$23.47). Of products, 40% (26 of 65) did not adhere to AAD guidelines (broad spectrum, SPF >=30, and water resistant) for sunscreens. Vehicles, AAD, and sunscreen type predicted a higher price per ounce. Cosmetic elegance was the most cited positive feature (198 of 325 [61%] comments) followed by product performance (146 of 325 [45%] comments) and skin type compatibility (78 of 325 [24%] comments). CONCLUSIONS AND RELEVANCE: In this cohort of highly rated sunscreen products, a significant proportion did not adhere to AAD guidelines, mostly attributable to a lack of water resistance. The most striking variation in this cohort was price, which varied by more than 3000%. Dermatologists should balance the importance of cosmetic elegance, cost, and AAD guidelines for sun protection in making their recommendations to consumers. PMID- 27385191 TI - Quantitative Evaluation of Site Energies and Their Fluctuations of Pigments in the Fenna-Matthews-Olson Complex with an Efficient Method for Generating a Potential Energy Surface. AB - We develop an efficient method to generate an accurate semiglobal potential energy surface of a molecule in condensed phases with low computational cost. We apply the method to the calculation of the site energies and their fluctuations of bacteriochlorophyll (BChl) a pigments in the Fenna-Matthews-Olson (FMO) complex using the density functional properly describing the ground and excited states of BChl a in solutions in our previous work (J. Phys. Chem. B 2014, 118, 10906-10918). The errors of the potential energies calculated from the present and QM/MM methods are small: ~1 kcal/mol for both the ground and excited states. The calculated site energies are in good agreement with the experimentally fitted results. The calculated spectral density also agrees with the experimentally available data. The spectral densities of BChl 2 and BChl 5 are much larger than those of the other five sites. The present method is expected to provide new insights into the efficient excitation energy transfer in light-harvesting antennas. PMID- 27385190 TI - Reformulating a Pharmacophore for 5-HT2A Serotonin Receptor Antagonists. AB - Several pharmacophore models have been proposed for 5-HT2A serotonin receptor antagonists. These typically consist of two aromatic/hydrophobic moieties separated by a given distance from each other, and from a basic amine. Although specified distances might vary, the models are relatively similar in their general construction. Because our preliminary data indicated that two aromatic (hydrophobic) moieties might not be required for such action, we deconstructed the serotonin-dopamine antipsychotic agent risperidone (1) into four smaller structural fragments that were thoroughly examined in 5-HT2A receptor binding and functional (i.e., two-electrode voltage clamp (TEVC) and intracellular calcium release) assays. It was apparent that truncated risperidone analogues behaved as antagonists. In particular, 6-fluoro-3-(1-methylpiperidin-4-yl)benzisoxazole (4) displayed high affinity for 5-HT2A receptors (Ki of ca. 12 nM) relative to risperidone (Ki of ca. 5 nM) and behaved as a potent 5-HT2A serotonin receptor antagonist. These results suggest that multiple aromatic (hydrophobic) moieties are not essential for high-affinity 5-HT2A receptor binding and antagonist activity and that current pharmacophore models for such agents are very much in need of revision. PMID- 27385193 TI - Dissipativity analysis of stochastic memristor-based recurrent neural networks with discrete and distributed time-varying delays. AB - In this paper, based on the knowledge of memristor-based recurrent neural networks (MRNNs), the model of the stochastic MRNNs with discrete and distributed delays is established. In real nervous systems and in the implementation of very large-scale integration (VLSI) circuits, noise is unavoidable, which leads to the stochastic model of the MRNNs. In this model, the delay interval is decomposed into two subintervals by using the tuning parameter alpha such that 0 < alpha < 1. By constructing proper Lyapunov-Krasovskii functional and employing direct delay decomposition technique, several sufficient conditions are given to guarantee the dissipativity and passivity of the stochastic MRNNs with discrete and distributed delays in the sense of Filippov solutions. Using the stochastic analysis theory and Ito's formula for stochastic differential equations, we establish sufficient conditions for dissipativity criterion. The dissipativity and passivity conditions are presented in terms of linear matrix inequalities, which can be easily solved by using Matlab Tools. Finally, three numerical examples with simulations are presented to demonstrate the effectiveness of the theoretical results. PMID- 27385192 TI - Efficacy and safety of triple therapy with dapagliflozin add-on to saxagliptin plus metformin over 52 weeks in patients with type 2 diabetes. AB - We previously reported that dapagliflozin versus placebo as add-on to saxagliptin plus metformin resulted in greater reductions in glycated haemoglobin (A1C), fasting plasma glucose (FPG) and body weight (BW) after 24 weeks of treatment in patients with type 2 diabetes (T2D). Here we report results after 52 weeks of treatment. Patients stabilized on open-label metformin and saxagliptin 5 mg/day for 8-16 weeks were randomized to placebo or dapagliflozin 10 mg/day plus open label saxagliptin plus metformin for 52 weeks. Changes from baseline to week 52 were greater with dapagliflozin versus placebo in A1C (-0.74% vs. 0.07%), FPG ( 27 vs. 10 mg/dL) and BW (-2.1 vs. -0.4 kg). More patients achieved A1C <7% with dapagliflozin (29.4%) versus placebo (12.6%). Adverse events were similar with dapagliflozin (66%) and placebo (71%), and hypoglycaemia was rare (<=2%). Genital infections occurred more often with dapagliflozin (6%) than with placebo (1%); frequency of urinary tract infections was similar between the two groups (9% vs. 10%). Triple therapy with dapagliflozin add-on to saxagliptin plus metformin is a durable, effective and well-tolerated intervention for the treatment of T2D. PMID- 27385194 TI - The formation mechanism of eutectic microstructures in NiAl-Cr composites. AB - NiAl-based eutectic alloys, consisting of an ordered bcc matrix (B2) and disordered bcc fibers (A2), have been a subject of intensive efforts aimed at tailoring the properties of many of the currently used nickel-based superalloys. A thermodynamic phase field model was developed on a thermodynamic foundation and fully integrated with a thermo-kinetic database of the Ni-Al-Cr ternary system to elucidate the resulting peculiar eutectic microstructure. Invoking a variation of the liquid/solid interfacial thickness with temperature, we simulated the characteristic sunflower-like eutectic microstructures in the NiAl-Cr composites, consistent with experimental observations. The mechanism that governs the formation of the peculiar eutectic morphology was envisioned from the modeled evolutions associated with six sequential steps. Our calculations show that the conditional spinodal decomposition occurring in sequence could further trim and revise the microstructure of the eutectics by generating fine-domain structures, thereby providing an additional method to explore the novel NiAl-based eutectic composites with tunable properties at elevated temperatures. PMID- 27385195 TI - Influence of thermal stimulation during the late phase of incubation on hatching results and post-hatch broiler performance under commercial conditions. AB - Two experiments, which differed in breeder age, strain and season, were conducted to study the influence of low-intensity, short-duration thermal stimuli during the late phase of incubation on hatchability and performance. The first experiment conducted in April-June used eggs from Cobb * Ross broiler breeders at 35-41 weeks of age and the second experiment performed in February-April used eggs from Hubbard * Cobb broiler breeders at 49-53 weeks of age. Eggs in the test group had the same physical environment as eggs in the control group except that incubation temperature was increased by 1C for 2 h/d above the control group from 18 to 20 d of incubation (DI). The results demonstrated that thermal stimulation of 1C for 2 h/d above control incubation temperature during 18-21DI did not have any adverse effects on hatch and post-hatch performance of broilers. In both experiments, treatment did not significantly alter the secondary sex ratio in hatched chickens, but hatch residue showed that the proportion of unhatched male embryos was significantly lower in the test groups than in the control groups. In the first experiment, thermal stimulation improved feed conversion by 1.82% compared with the control. PMID- 27385196 TI - Thrombin generation assay: interactions between chronic inflammation and haemostasis in patients with autoimmune diseases. AB - OBJECTIVES: Growing evidences show a direct link between inflammation and activation of haemostasis. That could increase thrombotic and cardiovascular risk in patients with active autoimmune diseases such as rheumatoid arthritis (RA) and systemic sclerosis (SSc). The aim of this study was to evaluate a possible hypercoagulable condition in RA and SSc patients, using the thrombin generation assay (TGA). METHODS: TGA was assessed in 44 RA [33 with active disease (actRA) and 11 inactive (non-actRA)], 25 SSc patients and 41 healthy controls using a fluorimetric technique and the TGA RB Low reagent. The Lag time (tLag), the time to thrombin peak (tPeak), the maximal concentration of formed thrombin (Peak), the velocity of thrombin generation (velocity) and the total amount of thrombin generated (AUC) were determined. RESULTS: As compared to the control group, tLag was found to be significantly reduced both in patients with actRA (p=0.0001) and non-actRA (p=0.01); tPeak was found to be reduced in actRA patients (p=0.0002). Similarly, as compared to healthy subjects, Peak and AUC were found to be increased in actRA patients (p=0.01; p=0.002), as well as D-dimer (p=0.01). Analysing SSc vs RA, a higher Peak and AUC were detected in RA patients. CONCLUSIONS: The TGA profile identified in actRA patients (decreased tLag and tPeak combined with higher thrombin peak and greater AUC) reflects a hypercoagulable state that could make patients more susceptible to develop a cardiovascular disease. PMID- 27385197 TI - Interprofessional Collaboration to Improve Discharge from Skilled Nursing Facility to Home: Preliminary Data on Postdischarge Hospitalizations and Emergency Department Visits. AB - An interprofessional collaborative practice model was established at Hennepin County Medical Center to improve discharge management from the transitional care unit of the skilled nursing facility (SNF) to home. The practice model involves a geriatrician, nurse practitioner, and pharmacist who care for individuals at a community-based SNF. Before SNF discharge, the pharmacist conducts a chart and in person medication review and collaborates with the nurse practitioner to determine the discharge medication regimen. The pharmacist's review focuses on assessing the indication, safety, effectiveness, and convenience of medications. The pharmacist provides follow-up in-home or over the telephone 1 week after SNF discharge, focusing on reviewing medications and assessing adherence. Hospitalizations and emergency department (ED) visits 30 days after SNF discharge of individuals who received care from this model was compared with those of individuals who received usual care from a nurse practitioner and geriatrician. From October 2012 through December 2013, the intervention was delivered to 87 individuals, with 189 individuals serving as the control group. After adjusting for age, sex, race, and payor, those receiving the intervention had a lower risk of ED visits (odds ratio (OR) = 0.46, 95% confidence interval (CI) = 0.22-0.97), although there was no significant difference in hospitalizations (OR = 0.47, 95% CI = 0.21-1.08). The study suggests that an interprofessional approach involving a pharmacist may be beneficial in reducing ED visits 30 days after SNF discharge. PMID- 27385199 TI - Royal Society of Chemistry Prizes and Awards 2016. PMID- 27385198 TI - Monitoring of adenovirus (ADV)-specific T cells in a boy with ADV pneumonia and disseminated disease after lung transplantation. AB - Human adenovirus (ADV) infections are the cause of severe morbidity and mortality in transplant recipients. Cidofovir (CDV) is the current standard antiviral treatment. We report the case of a 3-year-old boy after lung transplantation with severe ADV sepsis, who was monitored for ADV-specific T cells during his disease and recovery. A strong increase in ADV-specific T cells was accompanied by resolution of ADV in blood and bronchoalveolar lavage fluid. Antiviral treatment with CDV was individually adapted according to anti-ADV immune responses, which provides a new method for tailoring antiviral treatment in lung transplant recipients. PMID- 27385200 TI - Magnetic resonance imaging features of esthesioneuroblastoma in three dogs and one cat. AB - OBJECTIVE: Esthesioneuroblastoma is a rare malignant intranasal tumor that originates from the olfactory neuroepithelium of the upper nasal cavity, and can destroy the cribriform plate and expand into the neurocranium. Descriptions of the magnetic resonance features of esthesioneuroblastomas in animals are scarce. The objectives of this study were to report the magnetic resonance imaging features of esthesioneuroblastomas in order to determine distinct imaging characteristics that may help distinguish it from other intracranial tumor types. MATERIAL AND METHODS: Magnetic resonance images of four patients with confirmed esthesioneuroblastomas were reviewed and compared with previously reported cases. RESULTS: The esthesioneuroblastomas appeared as oval-shaped, solitary lesions in the caudal nasal cavity that caused osteolysis of the cribriform plate and extended into the brain in all cases. Signal intensity was variable. Contrast enhancement was mild and varied from homogeneous to heterogeneous. A peripheral cystic component was found in two patients and was reported in only one previous case. Mass effect and white matter edema were marked to severe. Osteolysis of facial bones and extension into the facial soft tissues or retrobulbar space were not present in any of the cases, although this has been reported in the literature. CONCLUSION: A definitive diagnosis of esthesioneuroblastoma based on signal intensity or contrast behavior was not possible. Nevertheless, the presence of a mass in the caudal nasal cavity with extension into the neurocranium seems to be a feature highly suspicious of esthesioneuroblastoma. In contrast to other extra-cranial lesions, the extra-cranial mass was relatively small and destruction of facial bones seems to be rare. PMID- 27385201 TI - Correction: A Genetic Screen Identifies a Requirement for Cysteine-Rich-Receptor Like Kinases in Rice NH1 (OsNPR1)-Mediated Immunity. AB - [This corrects the article DOI: 10.1371/journal.pgen.1006049.]. PMID- 27385202 TI - [Carpus and distal radioulnar joint : Clinical and radiological examination]. AB - A precise medical history and specific symptom-oriented clinical tests of the wrist joint should always precede any radiological, computed tomography (CT) or magnetic resonance imaging (MRI) diagnostics. In many cases, specific clinical tests of the wrist joint allow at least a preliminary diagnosis, which can be supported by standard radiography using correct projections. A systematic approach is recommended covering the radiocarpal, midcarpal, ulnocarpal and distal radioulnar joints. Exact identification of the palpable anatomic landmarks is mandatory for correct application and interpretation of the various clinical tests. The results of the clinical tests in combination with radiological imaging can often detect precisely ruptures of distinct wrist joint ligaments and localized arthritis. PMID- 27385204 TI - Pudendal nerve testing. PMID- 27385203 TI - [Ligamentous knee injuries in children and adolescents]. AB - Due to an increase in sporting activities, the number of injuries of the immature knee is continuously increasing. These injuries necessitate a special approach regarding the particular anatomical situation with open growth plates. Three of the most commonly occurring injuries are rupture of the anterior cruciate ligament, patella dislocation and meniscus injuries. The clinical results for conservative treatment of ruptures of the anterior cruciate ligament in the growth phase are inferior to operative treatment. Transepiphyseal reconstruction has been shown to be a safe treatment method and provides good clinical results. Therapy of patella instability in children has shown poor results and new surgical techniques have been introduced to perform an anatomical reconstruction of the medial patellofemoral ligament as well as to improve distal alignment. Isolated injuries to the meniscus are rare and discoid meniscus is a special phenomenon occurring in infancy. Meniscus injuries should be treated with primary sutures rather than resection. A discoid meniscus should be resected with extreme caution and anatomically reconstructed. PMID- 27385205 TI - The effect of a postoperative quality improvement program on outcomes in colorectal surgery in a community hospital. AB - PURPOSE: The aim of this study was to evaluate whether implementation of a comprehensive quality improvement program was associated with improved outcomes in patients undergoing oncological colorectal surgery in a non-academic, non referral community hospital. METHODS: The quality improvement program (QIP) was introduced in January 2011 and consisted of the following interventions: (1) avoidance of postoperative nonsteriodal anti-inflammatory drugs; (2) normovolemia was pursued pre- and postoperatively; (3) non-resectional surgery if possible, in patients over 80 with ASA 3 or 4 classification; and (4) a standardized, postoperative surveillance protocol was introduced, with CRP determination day 2 and 4, and if necessary subsequent abdominal CT with rectal contrast to reduce delay in diagnosis of complications. From a prospectively maintained database of 488 patients undergoing colorectal surgery between 2009 and 2014, postoperative outcomes of patients operated before and after implementation of the program were compared. RESULTS: The severe complication rate (Clavien-Dindo >3b) decreased significantly (25.0 vs. 13.7 %; p < .001) after implementation of the QIP program. The mortality rate dropped from 8.7 to 2.6 % (p = .003). The percentage of anastomotic leakage was 9.6% before QIP implementation and 4.2% after (p = .013). Median length of hospital stay decreased from 9 (IQR 5-19) to 7 days (IQR 4-12) (p < .001). Multivariate analyses showed that surgery after implementation of the program was a strong independent predictor for less major complications (OR 0.54, 95 % CI 0.32-0.88). CONCLUSIONS: A significant decrease in major complications and mortality was observed after introduction of a relative simple quality improvement program. PMID- 27385206 TI - Modular Artificial Cupredoxins. AB - Cupredoxins are electron-transfer proteins that have active sites containing a mononuclear Cu center with an unusual trigonal monopyramidal structure (Type 1 Cu). A single Cu-Scys bond is present within the trigonal plane that is responsible for its unique physical properties. We demonstrate that a cysteine containing variant of streptavidin (Sav) can serve as a protein host to model the structure and properties of Type 1 Cu sites. A series of artificial Cu proteins are described that rely on Sav and a series of biotinylated synthetic Cu complexes. Optical and EPR measurements highlight the presence of a Cu-Scys bond, and XRD analysis provides structural evidence. We further provide evidence that changes in the linker between the biotin and Cu complex within the synthetic constructs allows for small changes in the placement of Cu centers within Sav that have dramatic effects on the structural and physical properties of the resulting artificial metalloproteins. These findings highlight the utility of the biotin-Sav technology as an approach for simulating active sites of metalloproteins. PMID- 27385207 TI - Divergent Diffusion Coefficients in Simulations of Fluids and Lipid Membranes. AB - We investigate the dependence of single-particle diffusion coefficients on the size and shape of the simulation box in molecular dynamics simulations of fluids and lipid membranes. We find that the diffusion coefficients of lipids and a carbon nanotube embedded in a lipid membrane diverge with the logarithm of the box width. For a neat Lennard-Jones fluid in flat rectangular boxes, diffusion becomes anisotropic, diverging logarithmically in all three directions with increasing box width. In elongated boxes, the diffusion coefficients normal to the long axis diverge linearly with the height-to-width ratio. For both lipid membranes and neat fluids, this behavior is predicted quantitatively by hydrodynamic theory. Mean-square displacements in the neat fluid exhibit intermediate regimes of anomalous diffusion, with t ln t and t(3/2) components in flat and elongated boxes, respectively. For membranes, the large finite-size effects, and the apparent inability to determine a well-defined lipid diffusion coefficient from simulation, rationalize difficulties in comparing simulation results to each other and to those from experiments. PMID- 27385208 TI - Just add water: cannabinoid discrimination in a water T-maze with FAAH(-/-) and FAAH(+/+) mice. AB - Incomplete overlap in the discriminative stimulus effects of Delta tetrahydrocannabinol (THC) and the endocannabinoids, anandamide (AEA) and 2 arachidonoylglycerol has been reported in food-reinforced tasks. The aim of this study was to examine cannabinoid discriminative stimulus effects in a nonappetitive procedure. Adult male mice lacking the gene for AEA's major metabolic enzyme, fatty acid amide hydrolase (FAAH), and FAAH mice were trained to discriminate THC or AEA in a water T-maze, in which the response was swimming to an escape platform on the injection-appropriate side. JZL184, a monoacylglycerol lipase inhibitor, was also tested. FAAH mice showed faster acquisition than FAAH mice. THC and AEA fully substituted, with only minor cross procedure potency variations. Incomplete substitution of JZL184 was observed in THC-trained FAAH mice in the water-maze task, as contrasted with full substitution in a food-reinforced nose-poke procedure. Stress-induced changes in AEA and/or 2-arachidonoylglycerol concentrations in the brain may have mediated this attenuation. JZL184 also partially substituted in AEA-trained FAAH mice in the water maze, suggesting incomplete overlap in the stimulus effects of AEA and JZL184. Through the use of a novel water-maze procedure, the present study supports the work of previous behavioral pharmacologists in showing the robustness of the discrimination paradigm. PMID- 27385209 TI - Co-expression modules of NF1, PTEN and sprouty enable distinction of adult diffuse gliomas according to pathway activities of receptor tyrosine kinases. AB - Inter-individual variability causing elevated signaling of receptor tyrosine kinases (RTK) may have hampered the efficacy of targeted therapies. We developed a molecular signature for clustering adult diffuse gliomas based on the extent of RTK pathway activities. Glioma gene modules co-expressed with NF1 (NF1-M), Sprouty (SPRY-M) and PTEN (PTEN-M) were identified, their signatures enabled robust clustering of adult diffuse gliomas of WHO grades II-IV from five independent data sets into two subtypes with distinct activities of RAS-RAF-MEK MAPK cascade and PI3K-AKT pathway (named RMPAhigh and RMPAlow subtypes) in a morphology-independent manner. The RMPAhigh gliomas were associated with poor prognosis compared to the RMPAlow gliomas. The RMPAhigh and RMPAlow glioma subtypes harbored unique sets of genomic alterations in the RTK signaling-related genes. The RMPAhigh gliomas were enriched in immature vessel cells and tumor associated macrophages, and both cell types expressed high levels of pro angiogenic RTKs including MET, VEGFR1, KDR, EPHB4 and NRP1. In gliomas with major genomic lesions unrelated to RTK pathway, high RMPA signature was associated with short survival. Thus, the RMPA signatures capture RTK activities in both glioma cells and glioma microenvironment, and RTK signaling in the glioma microenvironment contributes to glioma progression. PMID- 27385210 TI - Sunitinib enhances the antitumor responses of agonistic CD40-antibody by reducing MDSCs and synergistically improving endothelial activation and T-cell recruitment. AB - CD40-activating immunotherapy has potent antitumor effects due to its ability to activate dendritic cells and induce cytotoxic T-cell responses. However, its efficacy is limited by immunosuppressive cells in the tumor and by endothelial anergy inhibiting recruitment of T-cells. Here, we show that combining agonistic CD40 monoclonal antibody (mAb) therapy with vascular targeting using the tyrosine kinase inhibitor sunitinib decreased tumor growth and improved survival in B16.F10 melanoma and T241 fibrosarcoma. Treatment of tumor-bearing mice with anti CD40 mAb led to increased activation of CD11c+ dendritic cells in the tumor draining lymph node, while sunitinib treatment reduced vessel density and decreased accumulation of CD11b+Gr1+ myeloid derived suppressor cells. The expression of ICAM-1 and VCAM-1 adhesion molecules was up-regulated on tumor endothelial cells only when anti-CD40 mAb treatment was combined with sunitinib. This was associated with enhanced intratumoral infiltration of CD8+ cytotoxic T cells. Our results show that combining CD40-stimulating immunotherapy with sunitinib treatment exerts potent complementary antitumor effects mediated by dendritic cell activation, a reduction in myeloid derived suppressor cells and increased endothelial activation, resulting in enhanced recruitment of cytotoxic T-cells. PMID- 27385211 TI - Antitumor activity of the aurora a selective kinase inhibitor, alisertib, against preclinical models of colorectal cancer. AB - BACKGROUND: The Aurora kinases are a family of serine/threonine kinases comprised of Aurora A, B, and C which execute critical steps in mitotic and meiotic progression. Alisertib (MLN8237) is an investigational Aurora A selective inhibitor that has demonstrated activity against a wide variety of tumor types in vitro and in vivo, including CRC. RESULTS: CRC cell lines demonstrated varying sensitivity to alisertib with IC50 values ranging from 0.06 to > 5 umol/L. Following exposure to alisertib we observed a decrease in pAurora A, B and C in four CRC cell lines. We also observed an increase in p53 and p21 in a sensitive p53 wildtype cell line in contrast to the p53 mutant cell line or the resistant cell lines. The addition of alisertib to standard CRC treatments demonstrated improvement over single agent arms; however, the benefit was largely less than additive, but not antagonistic. METHODS: Forty-seven CRC cell lines were exposed to alisertib and IC50s were calculated. Twenty-one PDX models were treated with alisertib and the Tumor Growth Inhibition Index was assessed. Additionally, 5 KRAS wildtype and mutant PDX models were treated with alisertib as single agent or in combination with cetuximab or irinotecan, respectively. CONCLUSION: Alisertib demonstrated anti-proliferative effects against CRC cell lines and PDX models. Our data suggest that the addition of alisertib to standard therapies in colorectal cancer if pursued clinically, will require further investigation of patient selection strategies and these combinations may facilitate future clinical studies. PMID- 27385212 TI - Halofuginone and artemisinin synergistically arrest cancer cells at the G1/G0 phase by upregulating p21Cip1 and p27Kip1. AB - Combinational drug therapy is one of the most promising strategies in modern anticancer research. Traditional Chinese medicine (TCM) formulas represent a wealth of complex combinations proven successful over centuries of clinical application. One such formula used to treat a variety of diseases, including cancer, contains two herbs, whose main active components are Halofuginone (HF) and Artemisinin (ATS). Here we studied the anticancer synergism of HF and ATS in various cancer cell lines and in a xenograft nude mice model. We found that the HF-ATS combination arrested more cells at the G1/G0 phase than either one alone, with the concomitant increased levels of CDK2 inhibitors, p21Cip1 and p27Kip1. By knocking down p21Cip1 and p27Kip1 separately or simultaneously in HCT116 cells and MCF-7 cells, we found that p21Cip1 was required for HF induced G1/G0 arrest, whereas p21Cip1 and p27Kip1 were both required for ATS or HF-ATS combination mediated cell cycle arrest. Moreover, HF-ATS combination synergistically inhibited tumor growth in xenograft nude mice, and this was associated with the increased levels of p21Cip1 and p27Kip1. Collectively, these data indicate that the upregulation of p21Cip1 and p27Kip1 contributes to the synergistic anticancer effect of the HF-ATS combination. PMID- 27385213 TI - Anaplastic lymphoma kinase aberrations correlate with metastatic features in pediatric rhabdomyosarcoma. AB - Rhabdomyosarcoma (RMS) is the most frequent soft tissue tumor in childhood and arises from immature mesenchymal cells committed to skeletal muscle differentiation. Anaplastic Lymphoma Kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in several cancers. Moreover, ALK full-length receptor protein has been observed in RMS, although its clinical and functional significance is yet controversial. The role of ALK and its clinical relevance were investigated in a selected cohort of 74 FFPE pediatric RMS and a panel of RMS cell lines, evaluating its gene and protein status, utilizing Fluorescent In Situ Hybridization (FISH), immunohistochemistry (IHC) and Western blot approaches. Moreover, to get insight into its possible therapeutic relevance, effects of ALK silencing on cell proliferation, invasion and apoptosis were studied in RMS cells. ALK IHC positivity was significantly correlated with gene copy number gain, the alveolar subtype, PAX3/7-FOXO1 rearrangements, the presence of metastasis at diagnosis and a worse overall outcome. Furthermore, EML4-ALK fusion gene associated with higher protein expression was identified in an embryonal RMS. ALK silencing in RH30 ALK positive cells strongly inhibited invasion capability. Overall, our data suggest a potential role of ALK in pediatric RMS. PMID- 27385214 TI - Downregulation of HP1alpha suppresses proliferation of cholangiocarcinoma by restoring SFRP1 expression. AB - Heterochromatin protein 1alpha (HP1alpha) is a gene that mediates chromatin conformation, gene silencing and cancer progression. However, little is known regarding the impact of HP1alpha in the pathogenesis of cholangiocarcinoma (CCA). In the present study, we demonstrate that HP1alpha is significantly upregulated in CCA tissues and cell lines, while downregulation of HP1alpha leads to suppression of cell proliferation. Then we find that downregulation of HP1alpha can decrease H3K9me3 enrichment and DNA methylation rate of secreted frizzled related protein 1 (SFRP1) promoter, resulting in restoring the expression of SFRP1. Moreover, restoration of SFRP1 expression can suppress CCA cells proliferation. These results provide a mechanistic understanding of the role of HP1alpha in the pathogenesis of CCA and may offer a novel therapeutic target in this disease. PMID- 27385215 TI - CD1d expression on chronic lymphocytic leukemia B cells affects disease progression and induces T cell skewing in CD8 positive and CD4CD8 double negative T cells. AB - Chronic lymphocytic leukemia develops within a complex network driven by genetic mutations and microenvironmental interactions. Among the latter a complex interplay with the immune system is established by the clone. Next to a proposed recruitment of support from T and myeloid cells, potential anti-CLL immune reactions need to be subverted. By using TCL1 mice as a CLL model, we show that TCR-Vbeta7+ NK1.1+ T cells are overrepresented in this disease model and constitute a main subset of peripheral CD3+ cells with biased TCR usage, showing that these cells account for a major part for T cell skewing in TCL1 mice. Moreover, we show that overrepresentation is dependent on CD1d expression in TCL1 mice, implicating that these cells belong to a NKT-like cell fraction which are restricted to antigen presented by the MHC-like surface marker CD1d. Accordingly, we observed a high fraction of CD161+ cells within overrepresented T cells in CLL patients and we found downregulation of CD1d on the surface of CLL cells, both in TCL1 mice and patients. Finally, we show that in TCL1 mice, CD1d deficiency resulted in shortened overall survival. Our results point to an interaction between CLL and CD161+ T cells that may represent a novel therapeutic target for immune modulation. PMID- 27385216 TI - Accumulation of cytoplasmic Cdk1 is associated with cancer growth and survival rate in epithelial ovarian cancer. AB - Cyclin dependent kinase 1 (Cdk1) have previously reported correlation with cancer growth and a key regulator for cell cycle. Mostly, Cdk1's function of nucleus for cell cycle is well known to be associated with cancer, but cytoplasmic Cdk1's traits are not clearly identified, yet. We revealed that tissue microarray blocks of epithelial ovarian cancer (n = 249) showed increased level of cytoplasmic Cdk1 (p < 0.001), but not in nucleus (p = 0.192) of histologic cell type independently. On survival analysis, Cdk1 overexpression conferred a significantly worse prognosis in 5-year overall survival (Log-rank p = 0.028, Hazard ratio = 2.016, 95% CI = 1.097 to 4.635). Also, the expression of Cdk1 was increased in ovarian cancer cell lines and Gene Expression Omnibus datasets. When the expression and activity of Cdk1 were inhibited by si-Cdk1 or RO-3306 which is a potent Cdk1 inhibitor, the growth of ovarian cancer was diminished. Moreover, combined treatment with RO-3306 and cisplatin in ovarian cancer significantly elevated anti-cancer effects than single-agent treatment. In conclusion, cytoplasmic Cdk1 expression which was elevated in ovarian cancer predicts a poor overall survival. The inhibition of Cdk1 expression and activity reduced ovarian cancer growth. PMID- 27385217 TI - FNDC3B promotes cell migration and tumor metastasis in hepatocellular carcinoma. AB - Recurrence and metastasis are common in hepatocellular carcinoma (HCC) and correlate with poor prognosis. We investigated the role of fibronectin type III domain containing 3B (FNDC3B) in HCC metastasis. Overexpression of FNDC3B in HCC cell lines enhanced cell migration and invasion. On the other hand, knockdown of FNDC3B using short-hairpin RNA reduced tumor nodule formation in both intra- and extra-hepatic metastasis. High levels of FNDC3B were observed in metastatic HCCs and correlated with poor patient survival and shorter recurrence time. Mutagenesis and LC-MS/MS analyses showed that FNDC3B promotes cell migration by cooperating with annexin A2 (ANXA2). Furthermore, FNDC3B and ANXA2 expression correlated negatively with patient survival. Our results indicate that FNDC3B behaves like an oncogene by promoting cell migration. This suggests FNDC3B could serve as a biomarker and therapeutic target for HCC metastasis. PMID- 27385219 TI - Circulating cartilage oligomeric matrix protein in juvenile idiopathic arthritis. AB - OBJECTIVES: Raised serum cartilage oligomeric matrix protein (sCOMP) has been reported to predict erosive disease in early rheumatoid arthritis (RA). In juvenile idiopathic arthritis (JIA), subnormal sCOMP levels have been associated with ongoing inflammation and growth retardation. In this study we aimed to assess sCOMP, C-reactive protein (CRP), and insulin-like growth factor (IGF)-1 in children/adolescents with JIA and in referents. METHOD: We enrolled 52 JIA patients at planned outpatient visits and 54 inpatients with ongoing infection ('infection referents'). A total of 120 referents testing negative for immunoglobulin (Ig)E-mediated allergy ('IgE referents') served as controls. All serum samples were analysed for COMP, IGF-1, and CRP. RESULTS: The average sCOMP level was highest among the IgE referents and lowest among the infection referents. In the JIA patients, the level of sCOMP was not associated with the level of CRP or with clinical signs of disease activity. CONCLUSIONS: The results of this study do not support routine clinical analysis of sCOMP levels in patients with JIA. PMID- 27385218 TI - SEP enhanced the antitumor activity of 5-fluorouracil by up-regulating NKG2D/MICA and reversed immune suppression via inhibiting ROS and caspase-3 in mice. AB - Chemotherapy and immunotherapy are the main remedies used in cancer treatment. Because immunotherapy can not only reduce the toxicity of chemotherapeutics but also enhance antitumor effects in vivo, combining these two therapies is a trend that continues to gain more attention in clinic. SEP, a polysaccharide isolated from Strongylocentrotus nudus egg, has been reported to display antitumor activity by stimulating immune cells, including NK and T cells, via TLR2 and TLR4. In the present study, the synergistic effect between SEP and 5-fluorouracil (5-FU), a traditional cytotoxic drug, in vitro and in vivo was investigated. The results obtained indicated that SEP alone stimulated NK-92 cytotoxicity and coordinated with 5-FU to augment the cytotoxicity of NK-92 cells against HepG-2 or A549 cells in vitro. SEP promoted NK-92 activity by stimulating NKG2D and its downstream DAP10/PI3K/Erk signaling pathway. Additionally, 5-FU could increase MICA expression on HepG-2 or A549 cells and prevent membrane MICA from shedding as soluble MICA, which were abrogated in the tumor cells transfected with ADAM 10 overexpression plasmid. Moreover, in H22- or Lewis lung cancer (LLC)-bearing mouse models, SEP reversed 5-FU-induced atrophy and apoptosis in both the spleen and bone marrow in vivo by suppressing ROS generation and caspase-3 activation. All of these results highlight the potential for the combination of SEP and 5-FU in cancer therapy in the future. PMID- 27385220 TI - Superconductivity in alkali-doped fullerene nanowhiskers. AB - Superconductivity in alkali metal-doped fullerene nanowhiskers (C60NWs) was observed in K3.3C60NWs, Rb3.0C60NWs and Cs2.0Rb1.0C60NWs with transition temperatures at 17, 25 and 26 K, respectively. Almost full shielding volume fraction (~80%) was observed in K3.3C60NWs when subjected to thermal treatment at 200 degrees C for a duration of 24 h. In contrast, the shielding fraction of Rb3.0C60NWs and Cs2.0Rb1.0C60NWs were calculated to be 8% and 6%, respectively. Here we report on an extensive investigation of the superconducting properties of these AC60NWs (A = K3.3, Rb3.0 and Cs2.0Rb1.0). These properties are compared to the ones reported on the corresponding conventional (single-crystal or powder) K-doped fullerene. We also evaluated the critical current densities of these C60NWs using the Bean model under an applied magnetic field up to 50 kOe. PMID- 27385221 TI - Cochrane in CORR ((r)): Screening Women for Intimate Partner Violence in Healthcare Settings (Review). PMID- 27385223 TI - Erratum to: Continuous and Pulsatile Pediatric Ventricular Assist Device Hemodynamics with a Viscoelastic Blood Model. PMID- 27385222 TI - Is There a Difference in Revision Risk Between Metal and Ceramic Heads on Highly Crosslinked Polyethylene Liners? AB - BACKGROUND: The most common bearing surface used among primary THAs worldwide is a metal or ceramic femoral head that articulates against a highly crosslinked ultrahigh-molecular-weight polyethylene (HXLPE) acetabular liner. Despite their widespread use, relatively little is known about the comparative effectiveness of ceramic versus metal femoral heads with respect to risk of revision and dislocation as well as the role of head size in this relationship. QUESTIONS/PURPOSES: The purpose of this study was to evaluate the risk of (1) all cause revision in metal versus ceramic femoral heads when used with an HXLPE liner, including an evaluation of the effect of head size; and (2) dislocation in metal versus ceramic femoral heads when used with an HXLPE liner as well as an assessment of the effect of head size. METHODS: Data were collected as part of the Kaiser Permanente Total Joint Replacement Registry between 2001 and 2013. Patients in this study were on average overweight (body mass index = 29 kg/m2), 67 years old, mostly female (57%), and had osteoarthritis (93%) as the primary indication for surgery. The material of the femoral head (metal, ceramic) was crossed with head size (< 32, 32, 36, > 36 mm), yielding eight device groupings. Only uncemented devices were evaluated. The primary outcome was all-cause revision (n = 28,772) and the secondary outcome was dislocation within 1 year (n = 19,623). Propensity scores were used to adjust for potential confounding at the implant/patient level using between-within semiparametric survival models that control for surgeon and hospital confounding and adjust estimates for the within cluster correlation among observations on the response. RESULTS: For all-cause revision, there was no difference between ceramic versus metal (reference) heads in combination with an HXLPE liner (hazard ratio [HR] = 0.82 [0.65-1.04], p = 0.099). Smaller metal head sizes of < 32 mm were associated with increased risk of revision relative to 36 mm (HR = 1.66 [1.20-2.31], p = 0.002, adjusted p = 0.025). For dislocation, ceramic heads increased risk relative to metal at < 32 mm only (HR = 4.39 [1.72-11.19], p = 0.002, adjusted p = 0.020). Head sizes < 32 mm were associated with increased risk of dislocation relative to 36 mm for metal (HR = 2.99 [1.40-6.39], p = 0.005, adjusted p = 0.047) and ceramic heads (HR = 15.69 [6.07-40.55], p < 0.001, adjusted p < 0.001). CONCLUSIONS: The results did not provide evidence for use of one femoral head material over another when used with HXLPE liners for the outcome of revision, but for dislocation, metal performed better than ceramic with < 32-mm heads. Overall, the findings suggest increased risk of revision/dislocation with head sizes < 32 mm. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 27385224 TI - The BMJ should not tell us how to vote on Brexit. PMID- 27385225 TI - Synthesis of Recombinant P48 of Mycoplasma agalactiae by Site Directed Mutagenesis and its Immunological Characterization. AB - Contagious agalactia caused by Mycoplasma agalactiae is an economically important disease of sheep and goats and has been prevalent worldwide including India. The present study was undertaken to evaluate the membrane protein P48 of M. agalactiae for specific diagnosis of disease. For this, p48 gene of the organism was amplified by PCR and subjected to site directed mutagenesis to convert three TGA codons to TGG's and, subsequently, cloned into prokaryotic expression vector pPRO EX HTb. Purified recombinant P48 protein reacted to anti-P48 serum in western blotting, which confirmed its immunogenic nature. Furthermore, the immune blotting of the cell lysates from various Indian isolates of M. agalactiae against anti-P48 serum resulted in a single band at ~ 48 kDa among all isolates, indicating the conserved nature of P48 antigen in M. agalactiae. Also, the cross reactivity of P48 antigen among various Mycoplasma spp. was checked by western blotting which revealed reactivity only with M. agalactiae and M. bovis. Hence, this antigen could be exploited to differentiate M. agalactiae from other pathogenic Mycoplasma species except M. bovis. However, the inability of P48 to distinguish M. agalactiae from M. bovis does not downgrade the significance of P48 as the two species are usually host specific. PMID- 27385227 TI - ACA Coverage, Health Spending, And More. PMID- 27385226 TI - Experimental Study of Magnetic Multi-Walled Carbon Nanotube-Doxorubicin Conjugate in a Lymph Node Metastatic Model of Breast Cancer. AB - BACKGROUND The lymphatic system plays a significant role in the defense of a subject against breast cancer and is one of the major pathways for the metastasis of breast cancer. To improve the prognosis, many means, including surgery, radiotherapy, and chemotherapy, have been used. However, the combination of all these modalities has limited efficacy. Lymph nodes, therefore, have become an exceptionally potential target organ in cancer chemotherapy. MATERIAL AND METHODS A lymph node metastatic model of breast cancer was established in BALB/c mice. Magnetic multi-walled carbon nanotube carrier with good adsorption and lymph node targeting capacity was prepared and conjugated with doxorubicin to make the magnetic multi-walled carbon nanotube-doxorubicin suspension. Dispersions of doxorubicin, magnetic multi-walled carbon nanotube-doxorubicin, and magnetic multi-walled carbon nanotube were injected into lymph node metastatic mice to compare their inhibitory effects on tumor cells in vivo. Inhibition of these dispersions on EMT-6 breast cancer cells was detected via MTT assay in vitro. RESULTS Although no significant difference was found between the effects of doxorubicin and magnetic multi-walled carbon nanotube-doxorubicin with the same concentration of doxorubicin on EMT-6 breast cancer cells in vitro, in terms of sizes of metastatic lymph nodes and xenograft tumors, apoptosis in metastatic lymph nodes, and adverse reactions, the magnetic multi-walled carbon nanotube doxorubicin group differed significantly from the other groups. CONCLUSIONS The magnetic multi-walled carbon nanotube-doxorubicin clearly played an inhibitory role in lymph node metastases to EMT-6 breast cancer cells. PMID- 27385228 TI - As Zika Reaches US Shores, States And Cities Struggle To Respond. AB - Local health officials have been forced to make do with public health resources stretched thin. PMID- 27385229 TI - Secret Shoppers Find Access To Providers And Network Accuracy Lacking For Those In Marketplace And Commercial Plans. AB - The adequacy of provider networks for plans sold through insurance Marketplaces established under the Affordable Care Act has received much scrutiny recently. Various studies have established that networks are generally narrow. To learn more about network adequacy and access to care, we investigated two questions. First, no matter the nominal size of a network, can patients gain access to primary care services from providers of their choice in a timely manner? Second, how does access compare to plans sold outside insurance Marketplaces? We conducted a "secret shopper" survey of 743 primary care providers from five of California's nineteen insurance Marketplace pricing regions in the summer of 2015. Our findings indicate that obtaining access to primary care providers was generally equally challenging both inside and outside insurance Marketplaces. In less than 30 percent of cases were consumers able to schedule an appointment with an initially selected physician provider. Information about provider networks was often inaccurate. Problems accessing services for patients with acute conditions were particularly troubling. Effectively addressing issues of network adequacy requires more accurate provider information. PMID- 27385230 TI - Marketplace Subsidies: Changing The 'Family Glitch' Reduces Family Health Spending But Increases Government Costs. AB - Under the Affordable Care Act, if one family member has an employer offer of single coverage deemed to be affordable-that is, costing less than 9.66 percent of family income in 2016-then all family members are ineligible for tax credits for Marketplace coverage, even if the cost of providing coverage to the whole family is greater than 9.66 percent of income. More than six million people live in such families and as a result are ineligible for premium tax credits. These families face premiums that can amount to 15.8 percent of income, or 12.0 percent after the tax advantages of employer-sponsored health coverage are factored in. We modeled the potential impact of changing the affordability test to take into account the cost of family coverage. Doing so would reduce spending on premiums from 12.0 percent to 6.3 percent of income, significantly alleviating financial burdens, but would generate little additional coverage. We estimated the additional costs to the federal government for premium tax credits and cost sharing reductions to be between $3.7 billion and $6.5 billion in 2016. PMID- 27385231 TI - Evidence Suggests That The ACA's Tobacco Surcharges Reduced Insurance Take-Up And Did Not Increase Smoking Cessation. AB - To account for tobacco users' excess health care costs and encourage cessation, the Affordable Care Act (ACA) allowed insurers to impose a surcharge on tobacco users' premiums for plans offered on the health insurance exchanges, or Marketplaces. Low-income tax credits for Marketplace coverage were based on premiums for non-tobacco users, which means that these credits did not offset any surcharge costs. Thus, this policy greatly increased out-of-pocket premiums for many tobacco users. Using data for 2011-14 from the Behavioral Risk Factor Surveillance System, we examined the effect of tobacco surcharges on insurance status and smoking cessation in the first year of the exchanges' implementation, among adults most likely to purchase insurance from them. Relative to smokers who faced no surcharges, smokers facing medium or high surcharges had significantly reduced coverage (reductions of 4.3 percentage points and 11.6 percentage points, respectively), but no significant differences in smoking cessation. In contrast, those facing low surcharges showed significantly less smoking cessation. Taken together, these findings suggest that tobacco surcharges conflicted with a major goal of the ACA-increased financial protection-without increasing smoking cessation. States should consider these potential effects when deciding whether to limit surcharges to less than the federal maximum. PMID- 27385232 TI - Changes In Health Status And Care Use After ACA Expansions Among The Insured And Uninsured. AB - Following the Affordable Care Act's insurance expansion provisions in 2014, the average health status and use of health care within coverage groups has likely changed. Medicaid enrollees and the uninsured were both healthier in 2014 than those respective groups were in 2013. By contrast, those with individual private insurance coverage appeared less healthy as a group. PMID- 27385233 TI - Health Spending For Low-, Middle-, And High-Income Americans, 1963-2012. AB - US medical spending growth slowed between 2004 and 2013. At the same time, many Americans faced rising copayments and deductibles, which may have particularly affected lower-income people. To explore whether the health spending slowdown affected all income groups equally, we divided the population into income quintiles. We then assessed trends in health expenditures by and on behalf of people in each quintile using twenty-two national surveys carried out between 1963 and 2012. Before the 1965 passage of legislation creating Medicare and Medicaid, the lowest income quintile had the lowest expenditures, despite their worse health compared to other income groups. By 1977 the unadjusted expenditures for the lowest quintile exceeded those for all other income groups. This pattern persisted until 2004. Thereafter, expenditures fell for the lowest quintile, while rising more than 10 percent for the middle three quintiles and close to 20 percent for the highest income quintile, which had the highest expenditures in 2012. The post-2004 divergence of expenditure trends for the wealthy, middle class, and poor occurred only among the nonelderly. We conclude that the new pattern of spending post-2004, with the wealthiest quintile having the highest expenditures for health care, suggests that a redistribution of care toward wealthier Americans accompanied the health spending slowdown. PMID- 27385234 TI - Where The Money Goes: The Evolving Expenses Of The US Health Care System. AB - National health care expenditures constitute revenue to the health care system. However, little is known about how this revenue is distributed across sectors. This article calculates revenues and detailed expenditures for physicians' offices, hospitals, and outpatient care centers in 1997, 2002, 2007, and 2012, using a range of Census Bureau and Bureau of Labor Statistics sources. Between 1997 and 2012, spending on these three sectors rose by $580 billion, and employment rose by 1.7 million people. Just under half of all 2012 revenues were spent on labor compensation. The labor compensation share of spending declined slightly; within these sectors, the share of compensation paid to physicians and nurses increased. Although employment of nonprofessional labor grew during the study period, this group did not account for much of the sector's increased spending. The plurality of the 1997-2012 spending increase went to producers of purchased materials and services, which now account for more than one-third of payments. PMID- 27385235 TI - The Great Recession And Increased Cost Sharing In European Health Systems. AB - European health systems are increasingly adopting cost-sharing models, potentially increasing out-of-pocket expenditures for patients who use health care services or buy medications. Government policies that increase patient cost sharing are responding to incremental growth in cost pressures from aging populations and the need to invest in new health technologies, as well as to general constraints on public expenditures resulting from the Great Recession (2007-09). We used data from the Survey of Health, Ageing and Retirement in Europe to examine changes from 2006-07 to 2013 in out-of-pocket expenditures among people ages fifty and older in eleven European countries. Our results identify increases both in the proportion of older European citizens who incurred out-of-pocket expenditures and in mean out-of-pocket expenditures over this period. We also identified a significant increase over time in the percentage of people who incurred catastrophic health expenditures (greater than 30 percent of the household income) in the Czech Republic, Italy, and Spain. Poorer populations were less likely than those in the highest income quintile to incur an out-of pocket expenditure and reported lower mean out-of-pocket expenditures, which suggests that measures are in place to provide poorer groups with some financial protection. These findings indicate the substantial weakening of financial protection for people ages fifty and older in European health systems after the Great Recession. PMID- 27385236 TI - Private Sector An Important But Not Dominant Provider Of Key Health Services In Low- And Middle-Income Countries. AB - There is debate about the role of the private sector in providing services in the health systems of low- and middle-income countries and about how the private sector could help achieve the goal of universal health coverage. Yet the role that the private sector plays in the delivery of health services is poorly understood. Using data for the period 1990-2013 from 205 Demographic and Health Surveys in seventy low- and middle-income countries, I analyzed the use of the private sector for the treatment of diarrhea and of fever or cough in children, for antenatal care, for institutional deliveries, and as a source of modern contraception for women. I found that private providers were the dominant source of treatment for childhood illnesses but not for the other services. I also found no evidence of increased use of the private sector over time. There is tremendous variation in use of the private sector across countries and health services. Urban and wealthier women disproportionately use the private sector, compared to rural and poorer women. The private sector plays an important role in providing coverage, but strategies to further engage the sector, if they are to be effective, will need to take into consideration the variation in its use. PMID- 27385237 TI - An Insurer's Care Transition Program Emphasizes Medication Reconciliation, Reduces Readmissions And Costs. AB - Adverse drug events and the challenges of clarifying and adhering to complex medication regimens are central drivers of hospital readmissions. Medication reconciliation programs can reduce the incidence of adverse drug events after discharge, but evidence regarding the impact of medication reconciliation on readmission rates and health care costs is less clear. We studied an insurer initiated care transition program based on medication reconciliation delivered by pharmacists via home visits and telephone and explored its effects on high-risk patients. We examined whether voluntary program participation was associated with improved medication use, reduced readmissions, and savings net of program costs. Program participants had a 50 percent reduced relative risk of readmission within thirty days of discharge and an absolute risk reduction of 11.1 percent. The program saved $2 for every $1 spent. These results represent real-world evidence that insurer-initiated, pharmacist-led care transition programs, focused on but not limited to medication reconciliation, have the potential to both improve clinical outcomes and reduce total costs of care. PMID- 27385238 TI - Medical Marijuana Laws Reduce Prescription Medication Use In Medicare Part D. AB - Legalization of medical marijuana has been one of the most controversial areas of state policy change over the past twenty years. However, little is known about whether medical marijuana is being used clinically to any significant degree. Using data on all prescriptions filled by Medicare Part D enrollees from 2010 to 2013, we found that the use of prescription drugs for which marijuana could serve as a clinical alternative fell significantly, once a medical marijuana law was implemented. National overall reductions in Medicare program and enrollee spending when states implemented medical marijuana laws were estimated to be $165.2 million per year in 2013. The availability of medical marijuana has a significant effect on prescribing patterns and spending in Medicare Part D. PMID- 27385239 TI - Medicare Part D: Patients Bear The Cost Of 'Me Too' Brand-Name Drugs. AB - Prescription drugs are a major source of US health care expenditure. "Me too" brand-name medications contribute to the cost of drugs, which is substantial for consumers. In 2013 patient copayments averaged 10.5 times more for two commonly prescribed brand-name medications versus generic therapeutic alternatives. PMID- 27385240 TI - Share Of Specialty Drugs In Commercial Plans Nearly Quadrupled, 2003-14. AB - From 2003 to 2014 the proportion of specialty prescription drugs (defined as those reimbursed at $600 or more per thirty-day fill) nearly quadrupled. Over this time period, fills for specialty drugs increased by 198 percent and spending for the drugs increased by 292 percent, as percentages of total drug fills and spending. Median out-of-pocket spending increased by 46 percent for specialty drugs and decreased by 57 percent for nonspecialty drugs during this time. PMID- 27385241 TI - Early Efforts By Medicare Accountable Care Organizations Have Limited Effect On Mental Illness Care And Management. AB - People with mental illness use more health care and have worse outcomes than those without such illnesses. In response to incentives to reduce spending, accountable care organizations (ACOs) may therefore attempt to improve their management of mental illness. We examined changes in mental health spending, utilization, and quality measures associated with ACO contracts in the Medicare Shared Savings Program and Pioneer model for beneficiaries with mental illness, using Medicare claims for the period 2008-13 and difference-in-differences comparisons with local non-ACO providers. Pioneer contracts were associated with lower spending on mental health admissions in the first year of the contract, an effect that was attenuated in the second year. Otherwise, ACO contracts were associated with no changes in mental health spending or readmissions, outpatient follow-up after mental health admissions, rates of depression diagnosis, or mental health status. These results suggest that ACOs have not yet focused on mental illness or have been largely unsuccessful in early efforts to improve their management of it. PMID- 27385242 TI - The Impact Of Medicare ACOs On Improving Integration And Coordination Of Physical And Behavioral Health Care. AB - The accountable care organization (ACO) model holds the promise of reducing costs and improving the quality of care by realigning payment incentives to focus on health outcomes instead of service volume. One key to managing the total cost of care is improving care coordination for and treatment of people with behavioral health disorders. We examined qualitative data from ninety organizations participating in Medicare ACO demonstration programs from 2012 through 2015 to determine whether and how they focused on behavioral health care. These ACOs had mixed degrees of engagement in improving behavioral health care for their populations. The biggest challenges included a lack of behavioral health care providers, data availability, and sustainable financing models. Nonetheless, we found substantial interest in integrating behavioral health care into primary care across a majority of the ACOs. PMID- 27385243 TI - Ten-Year Trends In Treatment Services For Children With Attention Deficit Hyperactivity Disorder Enrolled In Medicaid. AB - Closing the gap between evidence-based clinical practice standards and their inclusion in routine practice continues to be a major goal of health policy reforms. This gap is especially large for the care of children with psychiatric disorders-especially those from low-income families, many of whom are insured through Medicaid. To address this gap, we analyzed trends over ten years (2001 10) from Medicaid claims data describing changes over time in medication, psychotherapy, and combined treatment services for children diagnosed with attention deficit hyperactivity disorder (ADHD). Over this time, more children received treatments that conformed to practice standards, including the use of combination treatments of medication and psychotherapy. Rates of combined treatment increased by 74 percent, rates of psychotherapy alone more than doubled, and rates of medication alone decreased by 18 percent. Rates of diagnoses without any reimbursed treatment decreased by 39 percent. These trends suggest increasing adherence to clinical practice standards by providers serving children with ADHD in the Medicaid population, although the quality of those services is unknown. PMID- 27385244 TI - Population Of US Practicing Psychiatrists Declined, 2003-13, Which May Help Explain Poor Access To Mental Health Care. AB - A large proportion of the US population suffers from mental illness. Limited access to psychiatrists may be a contributor to the underuse of mental health services. We studied changes in the supply of psychiatrists from 2003 to 2013, compared to changes in the supply of primary care physicians and neurologists. During this period the number of practicing psychiatrists declined from 37,968 to 37,889, which represented a 10.2 percent reduction in the median number of psychiatrists per 100,000 residents in hospital referral regions. In contrast, the numbers of primary care physicians and neurologists grew during the study period. These findings may help explain why patients report poor access to mental health care. Future research should explore the impact of the declining psychiatrist supply on patients and investigate new models of care that seek to integrate mental health and primary care or use team-based care that combines the services of psychiatrists and nonphysician providers for individuals with severe mental illnesses. PMID- 27385245 TI - The Number Of Health Information Exchange Efforts Is Declining, Leaving The Viability Of Broad Clinical Data Exchange Uncertain. AB - The diffusion of health information exchange (HIE), in which clinical data are electronically linked to patients in many different care settings, is a top priority for policy makers. To drive HIE, community and state efforts were federally funded to broadly engage providers in exchanging data in ways that improved patient care. To assess the current landscape, we conducted a national survey of community and state HIE efforts soon after federal funding ended. We found 106 operational HIE efforts that, as a group, engaged more than one-third of all US providers in 2014. However, the number of operational HIE efforts is down from 119 in 2012, representing the first decline observed since the tracking of these efforts began in 2006. Only half of operational efforts reported being financially viable, and all efforts reported a variety of barriers to continuation. These findings raise important questions about whether the current vision for HIE efforts will allow for the broad exchange of clinical data, or whether alternative approaches would be more successful. PMID- 27385246 TI - Engagement In Hospital Health Information Exchange Is Associated With Vendor Marketplace Dominance. AB - Health information exchange (HIE) is intended to enable better, more efficient health care by electronically transferring patient data across provider organizations. Many policy makers, including members of Congress, are concerned that some electronic health record (EHR) vendors may be impeding this effort by making cross-vendor HIE difficult. We used national data to assess how market dominance by EHR vendors was related to hospitals' engagement in HIE in 2012 and 2013. Across all levels of vendor market dominance, hospitals using EHR systems supplied by the dominant vendor engaged in an average of 45 percent more HIE activities than hospitals not using the dominant vendor. However, when the dominant vendor controlled a small proportion-20 percent-of the market, hospitals using the dominant vendor engaged in 59 percent more HIE activities than hospitals using a different vendor. Conversely, when the dominant vendor controlled 80 percent of the market, hospitals using that vendor engaged in only 25 percent more HIE activities than hospitals using a different vendor. In markets with low vendor dominance, hospitals may engage in less HIE with hospitals using other vendors' systems, compared to markets with high vendor dominance, because of high costs and competitive barriers. Policies designed to promote cross-vendor HIE may need to take local market competition into account. PMID- 27385247 TI - Declining Admission Rates And Thirty-Day Readmission Rates Positively Associated Even Though Patients Grew Sicker Over Time. AB - Programs from the Centers for Medicare and Medicaid Services simultaneously promote strategies to lower hospital admissions and readmissions. However, there is concern that hospitals in communities that successfully reduce admissions may be penalized, as patients that are ultimately hospitalized may be sicker and at higher risk of readmission. We therefore examined the relationship between changes from 2010 to 2013 in admission rates and thirty-day readmission rates for elderly Medicare beneficiaries. We found that communities with the greatest decline in admission rates also had the greatest decline in thirty-day readmission rates, even though hospitalized patients did grow sicker as admission rates declined. The relationship between changing admission and readmission rates persisted in models that measured observed readmission rates, risk-standardized readmission rates, and the combined rate of readmission and death. Our findings suggest that communities can reduce admission rates and readmission rates in parallel, and that federal policy incentivizing reductions in both outcomes does not create contradictory incentives. PMID- 27385248 TI - Emergency Department Death Rates Dropped By Nearly 50 Percent, 1997-2011. AB - Between 1997 and 2011, there was a nearly 50 percent reduction in US emergency department mortality rates for adults. This trend likely has many causes, related to advances in palliative, prehospital, and emergency care. PMID- 27385249 TI - Contrary To Conventional Wisdom, Physicians Abandoned A Breast Cancer Treatment After A Trial Concluded It Was Ineffective. AB - Conventional wisdom holds that physicians are slow to abandon ineffective medical practices. We evaluated this theory in the case of axillary lymph node dissection, a procedure to remove the lymph nodes near the breast to prevent the spread of breast cancer following breast-conserving surgery. A major trial conducted from 1999 to 2004, with results presented in 2010 and published in 2011, found that patients who met certain criteria could forgo axillary lymph node dissection. Using cancer registry data, we estimated that the proportion of patients undergoing axillary dissection declined by 32.6 percentage points after the trial was published. The decline began immediately after the trial was presented at a medical conference. The rapid decline in the use of axillary dissection belies the common belief that practice patterns are slow to change in response to new evidence, and it highlights the value of trials of established medical practices to patients and the health system. PMID- 27385250 TI - Beating A Cancer Death Sentence. AB - A melanoma survivor describes his arduous-and costly-path to successful treatment and hope. PMID- 27385251 TI - Foundation Funding For The Nursing Profession. PMID- 27385252 TI - Errata. PMID- 27385253 TI - Assessment and validation of a defined fluid restriction protocol in the use of subcutaneous desmopressin for children with inherited bleeding disorders. AB - INTRODUCTION: Despite the availability of subcutaneous desmopressin (1-deamino-8 d-arginine vasopressin, SC-DDAVP) as a haemostatic agent for children with mild bleeding disorders, few publications specifically address the safety or efficacy of this mode of administration. AIM: Our aim was to assess whether a defined fluid restriction protocol was effective in preventing hyponatremia in children receiving perioperative SC-DDAVP, and to document adequate biological and clinical response in this setting. METHODS: We retrospectively analysed a cohort of children with mild bleeding disorders prescribed SC-DDAVP over a 5-year period following institution of a 'two-thirds maintenance' fluid restriction protocol. RESULTS: Sixty-nine patients received SC-DDAVP following this protocol, including 15 with mild haemophilia A, 49 with von Willebrand disease (VWD) and five with platelet storage pool disorder. In patients who underwent formal preoperative assessment a complete or partial response was observed in 28/29 with type 1 VWD and 14/15 with mild haemophilia A. Perioperative SC-DDAVP provided excellent haemostasis in all patients, with no requirement for factor concentrate or blood products. Mild asymptomatic hyponatremia was detected in seven children who received multiple doses of DDAVP (lowest sodium 129 mmol L(-1) ); however, adherence to the prescribed fluid restriction protocol was questionable in six of these cases. Symptomatic hyponatremia was not observed. CONCLUSION: Subcutaneous desmopressin was well-tolerated, with no serious side-effects observed, and good biological responses in preoperative trials. A two-thirds maintenance fluid regimen was effective at preventing symptomatic hyponatremia in our cohort, and is now the standard protocol for fluid restriction post-DDAVP administration in our centre. PMID- 27385254 TI - Emotions and Strategic Behaviour: The Case of the Ultimatum Game. AB - Human behaviour in economic interactions has attracted an increasing amount of attention over the last decades. The economic assumption that people would behave focusing on their own material self-interest was proved incomplete, once the empirical evidence consistently showed that many other motives may influence such behaviour. Therefore, models that can incorporate rational decision process as well as other intervening factors are a key issue to both understand the observations from economic experiments and to apply the lessons learned from them. In this paper, we incorporate the influence of emotions to the utility function in an explicit manner, using the Ultimatum Game as a case study. Our model is amenable to analytical study, and is connected with the Circumplex model of emotions and with Kahneman's two-system theory. The simplicity of the model allows to obtain predictions for the offers and acceptance thresholds. We study two specific examples, when the model parameters are distributed uniformly or normally, and show that in the latter case the results are already qualitatively correct. Although this work can be considered as a first approach, it includes what we believe are the main stylized facts, is able to qualitatively reproduce experimental results in a very simple manner, and can be straightforwardly extended to other games. PMID- 27385255 TI - [Unilateral Papillary Edema Due to Sinus Mucocele]. PMID- 27385256 TI - [Explantation of Multifocal Intraoular Lenses - Frequency, Causes and Course]. AB - PURPOSE: Multifocal intraocular lenses (MF-IOL) are implanted for visual rehabilitation after cataract operation and refractive lens exchange (RLE). In this retrospective study, the frequency, causes and course of MF-IOL explantation are investigated. SETTING: Private eye clinic, Cologne, Germany. METHODS: Between 2009 and 2014, a total of 1438 eyes were supplied with a hydrophobic, aspherical, diffractive, multifocal posterior chamber lens (PCL) of type: Acrysof ReSTOR and ReSTOR toric, with near additions of + 2.5, + 3.0 and + 4.0 (Alcon, Fort Worth, USA). 78 % (n = 1116 eyes) were indicated because of a cataract and 22 % (n = 322 eyes) as RLE. All procedures were either performed by OK or GG, as ultrasound phacoemulsification under topical anaesthesia. Since 2013, a femtosecond laser (LensX, Alcon, Fort Worth the USA) has been used in some cases. Data analysis was performed with the help of the digital patient's recordings. RESULTS: In a total of 12 cases, the MF-IOL needed to be explanted. Causes for the explantation were strong deviations from the expected target refraction (4 eyes), epiretinal gliosis accompanied by surgically membrane peeling (2 eyes), optical discomfort (waxy vision, 4 eyes), unstable toric lens due to a vast zonulolysis (1 eye), and 5 years post-implantation glistening (1 eye). The overall frequency of MF-IOL explantationen was 0.83 %. The frequency of explantations due to specific optical side effects and discomfort was 0.28 %. In all cases, 12 months post MF-IOL explantation recovery was achieved to full visual acuity. CONCLUSIONS: Diffractive MF-IOL of the type Alcon Acrysof ReSTOR are generall very well accepted. In only 0.28 % of all cases, was an explantation performed on grounds of optical discomfort. In the other cases, the causes for explantation were not related to the optical geometry of the MF-IOL. PMID- 27385257 TI - [Functional Results 3 Months after Implantation of an "Extended Range of Vision" Intraocular Lens]. AB - PURPOSE: Evaluation of the visual and refractive results 3 months after implantation of a diffractive extended range of vision (ERV) intraocular lens (IOL) during cataract surgery. METHODS: In a prospective multicentre study, patients with a calculated postoperative corneal astigmatism of <= 1.5 D received a diffractive ERV IOL (TECNIS Symfony, model ZXR00, Abbott Medical Optics, USA) during cataract surgery. After 3 months, the monocular and binocular corrected and uncorrected far, intermediate and near visual acuity, as well as refraction, were evaluated. RESULTS: 18 patients (36 eyes) with a mean age of 63.34 +/- 4.6 years underwent bilateral cataract surgery. After 3 months, the binocular uncorrected distance visual acuity (UDVA) of logMAR was - 0.05 +/- 0.11 and the corrected distance visual acuity (CDVA) of logMAR - 0.14 +/- 0.05. Binocular uncorrected intermediate (UIVA) and near visual acuity (UNVA) were logMAR - 0.09 +/- 0.02 and 0.19 +/- 0.09, respectively. A target refraction of +/- 0.75 D was reached by 89 % of the patients. CONCLUSION: Implantation of an extended range of vision intraocular lens offers an effective way for visual rehabilitation at far and intermediate distances. Near vision is still in a functional range. PMID- 27385258 TI - [E-PTFE Membrane for the Management of Perforated Corneal Ulcer]. AB - Purpose: To present the surgical management of perforated corneal ulcer using PRECLUDE(r) Pericardial Membrane, composed of expanded polytetrafluoroethylene (e PTFE; GORE-TEX(r)), as an alternative surgical procedure in patients at high risk of graft rejections and to evaluate side effects for a prolonged period. Patients and Methods: The study included all patients who were admitted to our department and underwent surgical repair of perforated corneal ulcer with the e-PTFE membrane between 2010 and 2015. In total, 8 patients (8 eyes) were enrolled. Medical records of all patients were retrospectively reviewed. The operation was performed under peribulbar anaesthesia. Non-absorbable, microporous, watertight 0.1 mm thick e-PTFE membrane was used to close the corneal ulcer. The membrane was cut to overlap the defect adequately and to achieve the desired tissue attachment without preparing the conjunctiva or superficial trephination of the cornea. The membrane was fixed to the healthy cornea with several non-absorbable sutures (Prolene(r) 10.0), in order to achieve the proper stress without wrinkling. Results: Five of 8 patients were treated for systemic immunological diseases. Sjogren's syndrome was diagnosed in 2 patients, granulomatosis with polyangiitis in one, vasculitis with a history of previous sclerokeratitis in one and systemic lupus erythematosus in one. In 2 patients, corneal perforation was observed as a complication of corneal infection and in one patient as a late complication of a severe chemical burn. Corneal perforations were successfully covered with e-PTFE membrane in all patients. E-PTFE membrane was well tolerated in all patients and the eye was always preserved. After 3 to 4 months, the membrane was removed in 7 patients. The underlying cornea was thin, firm, stable and vascularised. In one patient with Sjogren's syndrome, the e-PTFE membrane is still in place. Conclusion: Surgical management of perforated corneal ulcer using E-PTFE membrane may be the method of choice for eye preservation or for delayed corneal transplantation. Our results confirmed that the procedure is safe and effective, especially in high risk patients. After removing the membrane, penetrating keratoplasty can be performed as a definitive treatment in all eyes where an improvement in visual acuity is expected. PMID- 27385259 TI - [Hereditary Macular Dystrophies]. AB - Hereditary macular dystrophies are part of the group of inherited retinopathies caused by mutations of specific genes. Challenging features are their rarity, enormous clinical and genetic heterogeneity, unspecific visual disturbances, and often only mild initial fundus changes. The onset of macular dystrophies may occur at any age. They manifest in the macular region, whereas fundus changes can reach the mid periphery as well. In some cases, macular dystrophy can progress into generalised retinal dystrophy, depending on the severity of the causative mutations. Funduscopy alone is often insufficient for diagnosis. However, correct diagnosis is essential for the patient for counseling, low vision aids, support, and therapeutic options. Retinal imaging, with fundus autofluorescence, near infrared autofluorescence and optical coherence tomography, is very important, as it can show typical changes not visible on funduscopy. In cases where morphological changes are absent, retinal dysfunction must be detected by electrophysiological testing. There has been technical progress in molecular genetic testing in recent years. With the development of modern sequencing, an analysis for all known genes of hereditary retinal dystrophies has been established. The genetic defect can now be identified in more cases than before. However, a correct initial clinical diagnosis is still required for successful genetic analysis. The importance of a genetically confirmed diagnosis is increasing, as this is needed for patients who could have the chance in the near future to participate in therapeutic trials. PMID- 27385260 TI - Associations of Emotional Distress and Perceived Health in Persons With Atrial Fibrillation and Their Partners Using the Actor-Partner Interdependence Model. AB - Individual behavior affects and is affected by other people. The aim of this study was to examine if emotional distress in patients with atrial fibrillation (AF) and their spouses was associated with their own and their partner's perceived health. Participants included 91 dyads of patients and their spouses. Emotional distress was measured using the Hospital Anxiety and Depression Scale and perceived health was measured with the Short Form 36 Health Survey. The Actor Partner Interdependence Model was used for dyad-level analyses of associations, using structural equation modeling. Higher levels of anxiety and depression were associated with lower levels of perceived health in patients and spouses. Higher levels of depression in patients were associated with lower levels of vitality in spouses and vice versa. As AF patients and their spouses influence each other, health-care interventions should consider the dyad to address dyadic dynamics. This may benefit the health of the individual patient and of the couple. PMID- 27385261 TI - Thermoacoustic range verification using a clinical ultrasound array provides perfectly co-registered overlay of the Bragg peak onto an ultrasound image. AB - The potential of particle therapy due to focused dose deposition in the Bragg peak has not yet been fully realized due to inaccuracies in range verification. The purpose of this work was to correlate the Bragg peak location with target structure, by overlaying the location of the Bragg peak onto a standard ultrasound image. Pulsed delivery of 50 MeV protons was accomplished by a fast chopper installed between the ion source and the cyclotron inflector. The chopper limited the train of bunches so that 2 Gy were delivered in [Formula: see text]. The ion pulse generated thermoacoustic pulses that were detected by a cardiac ultrasound array, which also produced a grayscale ultrasound image. A filtered backprojection algorithm focused the received signal to the Bragg peak location with perfect co-registration to the ultrasound images. Data was collected in a room temperature water bath and gelatin phantom with a cavity designed to mimic the intestine, in which gas pockets can displace the Bragg peak. Phantom experiments performed with the cavity both empty and filled with olive oil confirmed that displacement of the Bragg peak due to anatomical change could be detected. Thermoacoustic range measurements in the waterbath agreed with Monte Carlo simulation within 1.2 mm. In the phantom, thermoacoustic range estimates and first-order range estimates from CT images agreed to within 1.5 mm. PMID- 27385262 TI - Van der Waals pressure and its effect on trapped interlayer molecules. AB - Van der Waals assembly of two-dimensional crystals continue attract intense interest due to the prospect of designing novel materials with on-demand properties. One of the unique features of this technology is the possibility of trapping molecules between two-dimensional crystals. The trapped molecules are predicted to experience pressures as high as 1 GPa. Here we report measurements of this interfacial pressure by capturing pressure-sensitive molecules and studying their structural and conformational changes. Pressures of 1.2+/-0.3 GPa are found using Raman spectrometry for molecular layers of 1-nm in thickness. We further show that this pressure can induce chemical reactions, and several trapped salts are found to react with water at room temperature, leading to two dimensional crystals of the corresponding oxides. This pressure and its effect should be taken into account in studies of van der Waals heterostructures and can also be exploited to modify materials confined at the atomic interfaces. PMID- 27385263 TI - Design, synthesis, insecticidal activity, and structure-activity relationship (SAR): studies of novel triazone derivatives containing a urea bridge group based on transient receptor potential (TRP) channels. AB - Numerous compounds containing urea bridge and biurea moieties are used in a variety of fields, especially as drugs and pesticides. To search for novel, environmentally benign and ecologically safe pesticides with unique modes of action, four series of novel triazone analogues containing urea, thiourea, biurea, and thiobiurea bridge, respectively, were designed and synthesized, according to various calcium ion channel inhibitors which act on transient receptor potential protein. Their structures were characterized by [Formula: see text] NMR, [Formula: see text] NMR, and HRMS. The insecticidal activities of the new compounds were obtained. The bioassay results indicated that compounds containing a thiourea bridge and a thiobiurea bridge exhibited excellent insecticidal activities against bean aphid. Specifically, compounds [Formula: see text], [Formula: see text], and [Formula: see text] exhibited 85, 90, and 95 % activities, respectively, at 10 mg/kg. Compounds [Formula: see text] (30 %), [Formula: see text] (35 %), [Formula: see text] (30 %), and [Formula: see text] (40 %) exhibited the approximate aphicidal activity of pymetrozine (30 %) at 5 mg/kg. In addition, some target compounds exhibited insecticidal activities against lepidopteran pests. From a molecular design standpoint, the information obtained in this study could help in the further design of new derivatives with improved insecticidal activities. PMID- 27385264 TI - Another morphogenetic movement on the map: Charting dorsal intercalation in C. elegans. AB - Dorsal intercalation is a coordinated cell migration event that rearranges hypodermal cells during C. elegans embryogenesis, and that resembles cell intercalation in many systems from flies to mice. Despite its conservation, the molecular mechanisms that govern dorsal intercalation in worms have remained elusive. Here, we comment on our recent publication, Walck-Shannon et al.,(1) which begins to spatially map the molecular requirements for intercalation. First, we provide a historical perspective on the factors that have previously hampered the study of dorsal intercalation. Next, we provide a summary of the molecular pathways identified in Walck-Shannon et al.,(1) pointing out surprises along the way. Finally, we consider the potential conservation of the molecular pathway we described and discuss future questions surrounding dorsal intercalation. Despite the challenges, dorsal intercalation is a process poised to advance our understanding of cell intercalation during morphogenesis throughout the animal kingdom. PMID- 27385265 TI - Disease activity indices in systemic sclerosis: a systematic literature review. AB - OBJECTIVES: Reviewing disease activity indices (DAI) in systemic sclerosis (SSc) and reporting their validation status. METHODS: Literature was systematically reviewed on studies documenting the development of DAI, assessing the validation status of DAI and studies using a DAI in their analysis. The qualitative and quantitative validation status of existing DAI was assessed based on OMERACT and on definitions of the American College of Rheumatology (ACR) committee on quality measures. RESULTS: Three DAI in SSc have been proposed in literature: the European Scleroderma Study Group (EScSG) activity index, the 12-point DAI and the Combined Response Index for Systemic Sclerosis (CRISS). The EScSG activity index is yet applied as an outcome measure in 48 different studies. The EScSG activity index and the CRISS are provisional partially validated DAI. CONCLUSIONS: Future studies are needed to fully validate the EScSG activity index and the CRISS and to assess the validation status of the 12-point DAI. PMID- 27385266 TI - DNA methylation based biomarkers in colorectal cancer: A systematic review. AB - Since genetic and epigenetic alterations influence the development of colorectal cancer (CRC), huge potential lies in the use of DNA methylation as biomarkers to improve the current diagnosis, screening, prognosis and treatment prediction. Here we performed a systematic review on DNA methylation-based biomarkers published in CRC, and discussed the current state of findings and future challenges. Based on the findings, we then provide a perspective on future studies. Genome-wide studies on DNA methylation revealed novel biomarkers as well as distinct subgroups that exist in CRC. For diagnostic purposes, the most independently validated genes to study further are VIM, SEPT9, ITGA4, OSM4, GATA4 and NDRG4. These hypermethylated biomarkers can even be combined with LINE1 hypomethylation and the performance of markers should be examined in comparison to FIT further to find sensitive combinations. In terms of prognostic markers, myopodin, KISS1, TMEFF2, HLTF, hMLH1, APAF1, BCL2 and p53 are independently validated. Most prognostic markers published lack both a multivariate analysis in comparison to clinical risk factors and the appropriate patient group who will benefit by adjuvant chemotherapy. Methylation of IGFBP3, mir148a and PTEN are found to be predictive markers for 5-FU and EGFR therapy respectively. For therapy prediction, more studies should focus on finding markers for chemotherapeutic drugs as majority of the patients would benefit. Translation of these biomarkers into clinical utility would require large-scale prospective cohorts and randomized clinical trials in future. Based on these findings and consideration we propose an avenue to introduce methylation markers into clinical practice in near future. For future studies, multi-omics profiling on matched tissue and non-invasive cohorts along with matched cohorts of adenoma to carcinoma is indispensable to concurrently stratify CRC and find novel, robust biomarkers. Moreover, future studies should examine the timing and heterogeneity of methylation as well as the difference in methylation levels between epithelial and stromal tissues. PMID- 27385267 TI - Photocatalytic Decarboxylative Hydroxylation of Carboxylic Acids Driven by Visible Light and Using Molecular Oxygen. AB - This paper discloses the first example of photocatalytic direct decarboxylative hydroxylation of carboxylic acids. It enables the conversion of a variety of readily available carboxylic acids to alcohols in moderate to high yields. This unprecedented protocol is accomplished under extremely mild reaction conditions using molecular oxygen (O2) as a green oxidant and using visible light as a driving force. PMID- 27385268 TI - Understanding perspectives of signalling mechanisms regulating PEBP1 function. AB - Phosphatidylethanolamine-binding protein 1 (PEBP1), also known as Raf kinase inhibitor protein, belongs to PEBP family of proteins. It is known to interact with many proteins that are mainly involved in pathways that monitor cell proliferation and differentiation. PEBP1 in many cells interacts with several pathways, namely MAPK, GRK2, NF-kB, etc. that keeps the cell proliferation and differentiation in check. This protein is expressed by many cells in humans, including neurons where it is predominantly involved in production of choline acetyltransferase. Deregulated PEBP1 is known to cause cancer, diabetic nephropathy and neurodegenerative diseases like Alzheimer's and dementia. Recent research led to the discovery of many drugs that mainly target the interaction of PEBP1 with its partners. These compounds are known to bind PEBP1 in its conserved domain which abrogate its association with interacting partners in several different pathways. We outline here the latest developments in understanding of PEBP1 function in maintaining cell integrity. Copyright (c) 2016 John Wiley & Sons, Ltd. SIGNIFICANCE OF THE STUDY: Phosphatidylethanolamine-binding protein is crucial in regulation of MAPK and PKC pathways. Its diverse roles, including regulating these pathways keep cell differentiation and proliferation in check. This review outlines some latest findings which greatly add to our current knowledge of phosphatidylethanolamine-binding protein. PMID- 27385269 TI - Is afatinib a treatment option for brain metastases in patients with EGFR mutation-positive non-small cell lung cancer? PMID- 27385270 TI - Factors affecting rural volunteering in palliative care - an integrated review. AB - To review factors shaping volunteering in palliative care in Australian rural communities using Australian and International literature. Identify gaps in the palliative care literature and make recommendations for future research. A comprehensive literature search was conducted using Proquest, Scopus, Sage Premier, Wiley online, Ovid, Cochran, Google Scholar, CINAHL and Informit Health Collection. The literature was synthesised and presented in an integrated thematic narrative. Australian Rural communities. While Australia, Canada, the United States (US) and the United Kingdom (UK) are leaders in palliative care volunteer research, limited research specifically focuses on volunteers in rural communities with the least occurring in Australia. Several interrelated factors influence rural palliative care provision, in particular an increasingly ageing population which includes an ageing volunteer and health professional workforce. Also current and models of palliative care practice fail to recognise the innumerable variables between and within rural communities such as distance, isolation, lack of privacy, limited health care services and infrastructure, and workforce shortages. These issues impact palliative care provision and are significant for health professionals, volunteers, patients and caregivers. The three key themes of this integrated review include: (i) Geography, ageing rural populations in palliative care practice, (ii) Psychosocial impact of end-end-of life care in rural communities and (iii) Palliative care models of practice and volunteering in rural communities. The invisibility of volunteers in rural palliative care research is a concern in understanding the issues affecting the sustainability of quality palliative care provision in rural communities. Recommendations for future Australian research includes examination of the suitability of current models of palliative care practice in addressing the needs of rural communities; the recruitment, training, ongoing education and support of volunteers in rural palliative care provision to ensure equitable care for all communities in Australia regardless of location. PMID- 27385271 TI - Sexual lifestyle among young adults with type 1 diabetes. AB - BACKGROUND: Sexual lifestyles including sexual activity, problems, satisfaction, and the formation and maintenance of relationships are greatly affected by physical health. Data are limited regarding the sexual lifestyle of adolescents and young adults with type 1 diabetes mellitus (T1DM). Fear of hypoglycemic episodes during sexual intercourse and intimacy issues can impact individuals with T1DM. The aim of this study was to assess sexual lifestyles of individuals with T1DM. METHODS: Fifty-three patients with T1DM, 27 (51%) males, mean +/- SD age 27.9 +/- 8.3 years completed the Hypoglycemia Fear Survey-II and the Sex Practices and Concerns questionnaire. RESULTS: Thirty-seven (70%) reported they never or almost never had concerns in their sexual lifestyles that were related to their diabetes. None experienced severe hypoglycemia during sex, but 21 (40%) reported occasional mild hypoglycemic events. More than two-thirds do not take any measures to prevent hypoglycemia before sex (decreasing insulin dose, snacks, and measuring blood glucose levels). Fear of hypoglycemia during sex was reported by 18 (35%); those who reported increased fear experienced mild hypoglycemic events during sex (61.1% vs 26.5%, P = .01), were singles (94.4% vs 64.7%, P = .02), and had higher scores on the Worries subscale of the Hypoglycemia Fear Survey-II (42.8 +/- 12.8 vs 34.9 +/- 10.5, P = .04) compared with those who did not. CONCLUSIONS: Among young people with T1DM, most do not have concerns regarding sex that are related to their diabetes, and most do not take specific measures before or after sex. One-third, however, fear of hypoglycemia during sex, mostly singles and those who experienced hypoglycemia in the past. Caregivers should be aware and address these concerns. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27385272 TI - Effects of a sleep education program with self-help treatment on sleeping patterns and daytime sleepiness in Japanese adolescents: A cluster randomized trial. AB - Subjective insufficient sleep and delayed sleep-wake patterns have been reported as the primary causes for daytime sleepiness, a reasonably significant and prevalent problem for adolescents worldwide. Systematic reviews have indicated that the success of sleep education programs has thus far been inconsistent, due to the lack of a tailored approach that allows for evaluation of individual differences in behavior patterns. One way to resolve this problem is to assess the individual sleep behaviors of adolescents by using a checklist containing the recommended behaviors for promoting sleep health. Such self-help education programs have already been implemented for elementary school children, school nurses and the elderly. The present study aimed to verify the effects of a sleep education program with supplementary self-help treatment, based on a checklist of sleep-promoting behaviors, in addition to evaluation of changes in sleeping patterns, sleep-promoting behaviors and daytime sleepiness in adolescents. A cluster randomized controlled trial involving 5 Japanese junior high schools was conducted, and 243 students (sleep education: n = 122; waiting list: n = 121; 50.6% female; 7th grade) were included in the final analysis. The sleep education group was provided with information on proper sleep health and sleep-promoting behaviors. The students in this group were asked to practice one sleep-promoting behavior as a goal for 2 weeks and to monitor their practice using sleep diaries. Both pre- and post-treatment questionnaires were administered to students in order to assess knowledge of sleep-promoting behaviors, sleeping patterns and daytime functioning. Students in the sleep education group showed significant improvement in their knowledge of sleep health (F1,121 = 648.05, p < 0.001) and in their sleep-promoting behaviors (F1,121 = 55.66, p < 0.001). Bedtime on both school nights (F1,121 = 50.86, p < 0.001) and weekends (F1,121 = 15.03, p < 0.001), sleep-onset latency (F1,121 = 10.26, p = 0.002), total sleep time on school nights (F1,121 = 12.45, p = 0.001), subjective experience of insufficient sleep (McNemar chi(2)(1) = 4.03, p = 0.045) and daytime sleepiness (McNemar chi(2)(1) = 4.23, p = 0.040) were also improved in the sleep education group. In contrast, no significant improvement in these variables was observed for students in the waiting-list group. In conclusion, the sleep education program with self help treatment was effective not only in increasing sleep knowledge but also in improving sleep-promoting behavior and sleeping patterns/reducing daytime sleepiness for students in the sleep education group, in comparison with the waiting-list group. PMID- 27385273 TI - Cell death caused by the synergistic effects of zinc and dopamine is mediated by a stress sensor gene Gadd45b - implication in the pathogenesis of Parkinson's disease. AB - The pathogenesis of Parkinson's disease (PD) is not completely understood, Zinc (Zn(2+) ) and dopamine (DA) have been shown to involve in the degeneration of dopaminergic cells. By microarray analysis, we identified Gadd45b as a candidate molecule that mediates Zn(2+) and DA-induced cell death; the mRNA and protein levels of Gadd45b are increased by Zn(2+) treatment and raised to an even higher level by Zn(2+) plus DA treatment. Zn(2+) plus DA treatment-induced PC12 cell death was enhanced when there was over-expression of Gadd45b and was decreased by knock down of Gadd45b. MAPK p38 and JNK signaling was able to cross-talk with Gadd45b during Zn(2+) and DA treatment. The synergistic effects of Zn(2+) and DA on PC12 cell death can be accounted for by an activation of the Gadd45b-induced cell death pathway and an inhibition of p38/JNK survival pathway. Furthermore, the in vivo results show that the levels of Gadd45b protein expression and phosphorylation of p38 were increased in the substantia nigra by the infusion of Zn(2+) /DA in the mouse brain and the level of Gadd45b mRNA is significantly higher in the substantia nigra of male PD patients than normal controls. The novel role of Gadd45b and its interactions with JNK and p38 will help our understanding of the pathogenesis of PD and help the development of future treatments for PD. Zinc and dopamine are implicated in the degeneration of dopaminergic neurons. We previously demonstrated that zinc and dopamine induced synergistic effects on PC12 cell death. Results from this study show that these synergistic effects can be accounted for by activation of the Gadd45b-induced cell death pathway and inhibition of the p38/JNK survival pathway. We provide in vitro and in vivo evidence to support a novel role for Gadd45b in the pathogenesis of Parkinson's disease. PMID- 27385274 TI - An international survey of patients living with spasticity. AB - PURPOSE: To better understand patient perspectives on the life impact of spasticity. METHODS: Global Internet survey (April 2014-May 2015) of 281 people living with spasticity. RESULTS: Respondents indicated that spasticity has a broad impact on their daily-life: 72% reported impact on quality of life, 44% reported loss of independence and 44% reported depression. Most respondents (64%) were cared for by family members, of whom half had stopped working or reduced their hours. Overall, 45% reported dissatisfaction with the information provided at diagnosis; main reasons were "not enough information" (67%) and "technical terminology" (36%). Respondents had high treatment expectations; 63% expected to be free of muscle spasm, 41% to take care of themselves and 36% to return to a normal routine. However, 33% of respondents had not discussed these expectations with their physician. The most common treatments were physiotherapy (75%), botulinum neurotoxin (BoNT, 73%) and oral spasmolytics (57%). Of those treated with BoNT, 47% waited >1 year from spasticity onset to treatment. CONCLUSIONS: This survey emphasises the broad impact of spasticity and highlights unmet needs in the patient journey. Improvements with regards to communication and the therapeutic relationship would be especially welcomed by patients, and would help manage treatment expectations. Implications of Rehabilitation Spasticity has broad impact on the lives of patients and their families that extends beyond the direct physical disability. Patients with spasticity need to be well informed about their condition and treatments available and should be given the opportunity to discuss their expectations. Physicians need to be aware of the patient's individual needs and expectations in order to better help them achieve their therapeutic goals. PMID- 27385275 TI - Metabolite profiling of Dioscorea (yam) species reveals underutilised biodiversity and renewable sources for high-value compounds. AB - Yams (Dioscorea spp.) are a multispecies crop with production in over 50 countries generating ~50 MT of edible tubers annually. The long-term storage potential of these tubers is vital for food security in developing countries. Furthermore, many species are important sources of pharmaceutical precursors. Despite these attributes as staple food crops and sources of high-value chemicals, Dioscorea spp. remain largely neglected in comparison to other staple tuber crops of tropical agricultural systems such as cassava (Manihot esculenta) and sweet potato (Ipomoea batatas). To date, studies have focussed on the tubers or rhizomes of Dioscorea, neglecting the foliage as waste. In the present study metabolite profiling procedures, using GC-MS approaches, have been established to assess biochemical diversity across species. The robustness of the procedures was shown using material from the phylogenetic clades. The resultant data allowed separation of the genotypes into clades, species and morphological traits with a putative geographical origin. Additionally, we show the potential of foliage material as a renewable source of high-value compounds. PMID- 27385276 TI - Regional differences in health, diet and weaning patterns amongst the first Neolithic farmers of central Europe. AB - Across much of central Europe, the Linearbandkeramik (LBK) represents the first Neolithic communities. Arising in Transdanubia around 5500 cal. BC the LBK spread west to the Rhine within two to three hundred years, carrying elements of a mixed agricultural economy and a relatively homogeneous material culture. Colonisation of new regions during this progress would have required economic adaptations to varied ecological conditions within the landscape. This paper investigates whether such adaptation at a local scale affected health patterns and altered the dietary habits of populations that otherwise shared a common cultural and biological origin. Analysis of non-specific stress (linear enamel hypoplasia, porotic hyperostosis, cribra orbitalia) within five LBK populations from across central Europe in conjunction with published carbon and nitrogen stable isotope data from each site revealed a high prevalence of porotic hyperostosis and cribra orbitalia in western populations that was associated with a lower animal protein intake. Hypoplastic enamel was more frequently observed in eastern populations however, and may reflect geographic differences in childhood morbidity and mortality as a result of variation in social practices relating to weaning. Local socio-economic adaptations within the LBK were therefore an important factor in the exposure of populations to non-specific stress. PMID- 27385278 TI - Functional characterization of a pheromone-binding protein from rice leaffolder Cnaphalocrocis medinalis in detecting pheromones and host plant volatiles. AB - Pheromone-binding proteins (PBPs) are believed to be involved in the recognition of semiochemicals. In the present study, western blot analysis, fluorescence binding characteristics and immunolocalization of CmedPBP4 from the rice leaffolder, Cnaphalocrocis medinalis, were investigated. Western blot analysis revealed that CmedPBP4 showed obvious antenna-specific expression patterns in female and male antenna, and made a clearly different sex-biased expression. Immunocytochemical labeling revealed that CmedPBP4 showed specific expression in the trichoid sensilla. Competitive fluorescence binding assays indicated that CmedPBP4 could selectively recognize three sex pheromone components (Z13-18:Ac, Z11-16:Al and Z13-18:OH) and eleven rice plant volatiles, including cyclohexanol, nerolidol, cedrol, dodecanal, ionone, (-)-alpha-cedrene, (Z)-farnesene, beta myrcene, R-(+)-limonene, (-)-limonene, and (+)-3-carene. Meanwhile the CmedPBP4 detection of sex pheromones and host odorants was pH-dependent. Our results, for the first time, provide further evidence that trichoid sensilla might be play an important role in detecting sex pheromones and host plant volatiles in the C. medinalis moth. Our systematic studies provided further detailed evidence for the function of trichoid sensilla in insect semiochemical perception. PMID- 27385280 TI - Peripartum Cardiomyopathy From a Genetic Perspective. AB - Peripartum cardiomyopathy (PPCM) is a rare, but life-threatening condition that occurs during the peripartum period in previously healthy women. Although its etiology remains unknown, potential risk factors include hypertensive disorders during pregnancy, such as preeclampsia, advanced maternal age, multiparity, multiple gestation, and African descent. Several cohort studies of PPCM revealed that the prevalence of these risk factors was quite similar. Clinically, approximately 40% of PPCM patients are complicated with hypertensive disorders during pregnancy. Because PPCM is a diagnosis of exclusion, heterogeneity is a common element in its pathogenesis. Recent genetic research has given us new aspects of the disease. PPCM and dilated cardiomyopathy (DCM) share genetic predisposition: 15% of PPCM patients were found to have genetic mutations that have been associated with DCM, and they showed a lower recovery rate. Other basic research using PPCM model mice suggests that predisposition genes related to both hypertensive and cardiac disorders via angiogenic imbalance may explain common elements of hypertensive disorders and PPCM. Furthermore, hypertensive disorders during pregnancy are now found to be a risk factor of not only PPCM, but also cardiomyopathy in the future. Understanding genetic variations allows us to stratify PPCM patients and to guide therapy. (Circ J 2016; 80: 1684-1688). PMID- 27385281 TI - Impaired Mechanics of Left Ventriculo-Atrial Coupling in Patients With Diabetic Nephropathy. AB - BACKGROUND: Diabetic nephropathy is independently associated with longitudinal systolic dysfunction of the left ventricle (LV) in asymptomatic diabetes mellitus (DM) patients with preserved LV ejection fraction (LVEF). However, the effect of diabetic nephropathy on left atrial (LA) function remains unknown. METHODS AND RESULTS: We studied 198 asymptomatic DM patients (LVEF >=50%). Diabetic nephropathy was defined as a protein level higher than for micro-albuminuria. LV global longitudinal strain (GLS) and LA strain were analyzed by 2D speckle tracking; 69 age-, sex-, and LVEF-matched controls were also studied. GLS and LA strain in systole (LAS-s) decreased significantly from normal controls to DM patients without (n=137) and with nephropathy (n=61), in that order. Furthermore, GLS, LAS-s, and LA strain in late diastole (LAS-a) were significantly lower in DM patients with macro-albuminuria (n=19) than in those with micro-albuminuria (n=42). Although 1 multivariate regression analysis identified albuminuria as an independent determinative factor of LAS-s among other relevant clinical background factors (beta=-0.16, P=0.002), another multivariate regression model for LAS-s+GLS (beta=0.40, P<0.001) showed that albuminuria was not a significant factor (beta=-0.02, P=0.68). Similarly, another multivariate regression model including GLS (beta=0.32, P<0.001) demonstrated that clinical features relevant for LAS-a, except for age, were not independent determinants of LAS-a. CONCLUSIONS: The cross-linked association of LA strain with GLS and albuminuria may be important for better understanding the development of diabetic cardiomyopathy. (Circ J 2016; 80: 1957-1964). PMID- 27385282 TI - Late Phase II Cardiac Rehabilitation, Which Is Adding Life to Years and Years to Life, Is Still Underused in Japan. PMID- 27385283 TI - Empirical model of human blood transverse relaxation at 3 T improves MRI T2 oximetry. AB - PURPOSE: We sought a human blood T2 -oximetery calibration curve over the wide range of hematocrits commonly found in anemic patients applicable with T2 relaxation under spin tagging (TRUST). METHODS: Blood was drawn from five healthy control subjects. Ninety-three in vitro blood transverse relaxation (T2b ) measurements were performed at 37 degrees C over a broad range of hematocrits (10 55%) and oxygen saturations (14-100%) at 3 Tesla (T). In vivo TRUST was performed on 35 healthy African American control subjects and 11 patients with chronic anemia syndromes. RESULTS: 1/T2 rose linearly with hematocrit (r2 = 0.96), for fully saturated blood. Upon desaturation, 1/T2 rose linearly with the square of the oxygen extraction, (1-Y)2 , and the slope was linearly proportional to hematocrit (r2 = 0.88). The resulting bilinear model between 1/T2 , (1-Y)2 , and hematocrit had a combined r2 of 0.96 and a coefficient of variation of 6.1%. Using the in vivo data, the bilinear model had significantly lower bias and variability than existing calibrations, particularly for low hematocrits. In vivo Bland Altman analysis demonstrated clinically relevant bias that was -6% (absolute saturation) for hematocrits near 30% and rose to + 6% for hematocrits near 45%. CONCLUSION: This work introduces a robust bilinear calibration model that should be used for MRI oximetry. Magn Reson Med 77:2364-2371, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27385285 TI - Effects of Neonicotinoid Pesticide Exposure on Human Health: A Systematic Review. AB - BACKGROUND: Numerous studies have identified detectable levels of neonicotinoids (neonics) in the environment, adverse effects of neonics in many species, including mammals, and pathways through which human exposure to neonics could occur, yet little is known about the human health effects of neonic exposure. OBJECTIVE: In this systematic review, we sought to identify human population studies on the health effects of neonics. METHODS: Studies published in English between 2005 and 2015 were searched using PubMed, Scopus, and Web of Science databases. No restrictions were placed on the type of health outcome assessed. Risk of bias was assessed using guidance developed by the National Toxicology Program's Office of Health Assessment and Translation. RESULTS: Eight studies investigating the human health effects of exposure to neonics were identified. Four examined acute exposure: Three neonic poisoning studies reported two fatalities (n = 1,280 cases) and an occupational exposure study of 19 forestry workers reported no adverse effects. Four general population studies reported associations between chronic neonic exposure and adverse developmental or neurological outcomes, including tetralogy of Fallot (AOR 2.4, 95% CI: 1.1, 5.4), anencephaly (AOR 2.9, 95% CI: 1.0, 8.2), autism spectrum disorder [AOR 1.3, 95% credible interval (CrI): 0.78, 2.2], and a symptom cluster including memory loss and finger tremor (OR 14, 95% CI: 3.5, 57). Reported odds ratios were based on exposed compared to unexposed groups. CONCLUSIONS: The studies conducted to date were limited in number with suggestive but methodologically weak findings related to chronic exposure. Given the wide-scale use of neonics, more studies are needed to fully understand their effects on human health. Citation: Cimino AM, Boyles AL, Thayer KA, Perry MJ. 2017. Effects of neonicotinoid pesticide exposure on human health: a systematic review. Environ Health Perspect 125:155-162; http://dx.doi.org/10.1289/EHP515. PMID- 27385286 TI - Mirror, mirror on the wall, who is the fairest of them all? PMID- 27385287 TI - Smuggling compassion into care: Is the NHS destined for system D? PMID- 27385284 TI - Immunophenotyping of rheumatoid arthritis reveals a linkage between HLA-DRB1 genotype, CXCR4 expression on memory CD4(+) T cells, and disease activity. AB - Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that leads to destructive arthritis. Although the HLA class II locus is the strongest genetic risk factor for rheumatoid arthritis, the relationship between HLA class II alleles and lymphocyte activation remains unclear. We performed immunophenotyping of peripheral blood mononuclear cells on 91 HLA-DRB1-genotyped RA patients and 110 healthy donors. The frequency of memory CXCR4(+)CD4(+) T cells, and not Th1 and Th17 cells, was significantly associated with disease severity by multiple linear regression analysis. RA patients with one or more susceptible HLA-DR haplotypes (shared epitope: SE) displayed a significantly higher frequency of memory CXCR4(+)CD4(+) T cells. Moreover, the frequency of memory CXCR4(+)CD4(+) T cells significantly correlated with the expression level of HLA-DR on B cells, which was elevated in RA patients with SE. In vitro analysis and transcriptomic pathway analysis suggested that the interaction between HLA-DR and T cell receptors is an important regulator of memory CXCR4(+)CD4(+) T cells. Clinically, a higher frequency of memory CXCR4(+)CD4(+) T cells predicted a better response to CTLA4-Ig. Memory CXCR4(+)CD4(+) T cells may serve as a powerful biomarker for unraveling the linkage between HLA-DRB1 genotype and disease activity in RA. PMID- 27385288 TI - Mixed mood states: time to adopt a 3D perspective? PMID- 27385289 TI - An Erudite Encounter with: Paul Grof. PMID- 27385291 TI - A high-sensitivity HPLC assay for measuring intracellular Na(+) and K(+) and its application to Plasmodium falciparum infected erythrocytes. AB - The measurement of intracellular ion concentrations, and the screening of chemical agents to identify molecules targeting ion transport, has traditionally involved low-throughput techniques. Here we present a novel HPLC method that allows the rapid, high-sensitivity measurement of cell Na(+) and K(+) content, demonstrating its utility by monitoring the ionic changes induced in the intracellular malaria parasite by the new spiroindolone antimalarial KAE609. PMID- 27385290 TI - Danshensu alleviates cardiac ischaemia/reperfusion injury by inhibiting autophagy and apoptosis via activation of mTOR signalling. AB - The traditional Chinese medicine Danshensu (DSS) has a protective effect on cardiac ischaemia/reperfusion (I/R) injury. However, the molecular mechanisms underlying the DSS action remain undefined. We investigated the potential role of DSS in autophagy and apoptosis using cardiac I/R injury models of cardiomyocytes and isolated rat hearts. Cultured neonatal rat cardiomyocytes were subjected to 6 hrs of hypoxia followed by 18 hrs of reoxygenation to induce cell damage. The isolated rat hearts were used to perform global ischaemia for 30 min., followed by 60 min. reperfusion. Ischaemia/reperfusion injury decreased the haemodynamic parameters on cardiac function, damaged cardiomyocytes or even caused cell death. Pre-treatment of DSS significantly improved cell survival and protected against I/R-induced deterioration of cardiac function. The improved cell survival upon DSS treatment was associated with activation of mammalian target of rapamycin (mTOR) (as manifested by increased phosphorylation of S6K and S6), which was accompanied with attenuated autophagy flux and decreased expression of autophagy- and apoptosis-related proteins (including p62, LC3-II, Beclin-1, Bax, and Caspase 3) at both protein and mRNA levels. These results suggest that alleviation of cardiac I/R injury by pre-treatment with DSS may be attributable to inhibiting excessive autophagy and apoptosis through mTOR activation. PMID- 27385292 TI - Large Orbital Magnetic Moment Measured in the [TpFe(III)(CN)3](-) Precursor of Photomagnetic Molecular Prussian Blue Analogues. AB - Photomagnetism in three-dimensional Co/Fe Prussian blue analogues is a complex phenomenon, whose detailed mechanism is not yet fully understood. Recently, researchers have been able to prepare molecular fragments of these networks using a building block synthetic approach from mononuclear precursors. The main objective in this strategy is to isolate the smallest units that show an intramolecular electron transfer to have a better understanding of the electronic processes. A prior requirement to the development of this kind of system is to understand to what extent electronic and magnetic properties are inherited from the corresponding precursors. In this work, we investigate the electronic and magnetic properties of the FeTp precursor (N(C4H9)4)[TpFe(III)(CN)3], (Tp being tris-pyrazolyl borate) of a recently reported binuclear cyanido-bridged Fe/Co complex. X-ray absorption spectroscopy and X-ray magnetic circular dichroism measurements at the Fe L2,3 edges (2p -> 3d) supported by ligand field multiplet calculations have allowed to determine the spin and orbit magnetic moments. Inaccuracy of the spin sum rule in the case of low-spin Fe(III) ion was demonstrated. An exceptionally large value of the orbital magnetic moment is found (0.9 MUB at T = 2 K and B = 6.5 T) that is likely to play an important role in the magnetic and photomagnetic properties of molecular Fe/Co Prussian blue analogues. PMID- 27385293 TI - Elbow arthroplasty: where are we today? A narrative review. AB - Background The elbow joint is a complex compound articulation, with a linking role within the upper limb kinematics. Its hinge function allows for proper placement of our working instrument (the hand) in the space surrounding us, directed by the shoulder joint. Both reliable mobility and stability are essential elements to allow for consistent bridging of the distance we aim to achieve in common daily activities. Sufficient flexion and extension are required to ensure both the patients' independence and the dignity. Next to the hinge, a radio-ulnar rotation with precise co-operation of forearm and wrist spin enhances the linking function with accurate precision instrument manipulation. Arthritis of the elbow joint or cubarthritis, whether primary or secondary, may not be as highly prevalent as hip or knee arthritis, but its impact on daily live certainly cannot be underestimated. Methods Current treatment options for failing cubarthritis are reviewed. Results Surgical techniques to reconstruct or replace the elbow joint are currently increasingly efficient with mounting long-term outcome reports. Debridement techniques including open or arthroscopic Outerbridge-Kashiwaghi procedure often delays joint replacement. Implants for joint arthroplasty focus on the ulna-humeral joint mostly with semi-constrained linked techniques, but there is a trend towards total joint replacement including the radiocapitellar joint. Conclusion In this independent review article, elbow joint failure due to cubarthritis and an overview of its current state-of-the-art orthopaedic treatment algorithm is presented, with its indications, advantages, risks and outcome. PMID- 27385294 TI - Superior mesenteric artery (Wilkie's) syndrome: a rare cause of upper gastrointestinal system obstruction. AB - Background Superior mesenteric artery syndrome (SMAS) results from the compression of the third part of the duodenum between the aorta and the proximal part of the superior mesenteric artery (SMA). Clinical presentation of SMAS is characterized by the dilatation of the proximal part of the third part of the duodenum. SMAS is a rare cause of the upper gastrointestinal system (UGS) obstruction. In this study, we aimed to present our clinical experience in the treatment of five patients with SMAS, which is a rare clinical condition requiring surgery. Patients and methods The retrospective study included five patients who were treated due to SMAS at our clinic between January 2010 and January 2014. Results All the patients were underweight, with a mean BMI of 15.73 (14-16). The clinical symptoms included epigastric pain after food intake, large volume bilious emesis, early satiety, failure to gain weight, indigestion, esophageal reflux, sense of fullness, and persistent weight loss. SMAS was diagnosed using barium meal studies, upper gastrointestinal endoscopy, abdominal ultrasonography, and CT angiography. Four patients underwent duodenojejunostomy and one patient was managed with gastrojejunostomy. No complication was observed during the postoperative period, and all the patients achieved significant improvement in symptoms. Conclusion SMAS is a rare cause of UGS obstruction, and the diagnosis of SMAS is often delayed. SMAS should be suspected in the differential diagnosis of the patients with unsubstantiated symptoms of persistent nausea, emesis, and significant weight loss. PMID- 27385295 TI - Neonatal gastric outlet obstruction by isolated pyloric atresia, an often forgotten diagnosis. AB - BACKGROUND: Pyloric atresia (PA) is a rare condition, and may be misdiagnosed and especially confused for duodenal atresia pre-operatively. We looked for clues to avoiding pre-operative misdiagnosis and hence allow the best neonatal medical and surgical management. METHODS: A retrospective case-note review was carried out of the five patients managed in four centres with the diagnosis of isolated PA. We focused on antenatal ultrasound findings, postnatal clinical and radiological features, operative findings, surgical procedures and outcomes. RESULTS: Four patients had polyhydramnios and one double bubble sign on antenatal ultrasound. After birth, non-bilious vomiting and upper abdominal distension were the main symptoms. Gastric decompression showed non-bilious gastric fluid. Radiological findings were a large gastric air bubble with no gas beyond in all cases. The diagnosis of duodenal atresia was postulated at first in all cases. The diagnosis of PA was established peroperatively. One patient referred late, died 13-day post operatively of cardiopulmonary failure secondary to a severe pneumonia that may be related to aspiration syndrome. Outcomes were otherwise satisfactory. CONCLUSIONS: Even though it is a rare diagnosis, PA has a specific clinical and radiological presentation underlined here that should be kept in mind when managing a neonate with a gastric outlet obstruction. PMID- 27385296 TI - Re-admissions for delayed complications after cytoreductive surgery and HIPEC. AB - BACKGROUND: Peritoneal metastasis (PM) is currently treated with the complex procedure of cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy (CRS + HIPEC). This procedure presents high morbidity and mortality rates, but they have only been examined in the immediate post-operative period. The aim of our study is to present, describe and analyze the post-operative events, secondary to a cytoreductive surgery and HIPEC procedure that occurs after the patients' discharge from the hospital. PATIENTS AND METHODS: We examine retrospectively 219 patients who were discharged from our hospital from the initial 230 patients with PM, who were operated on from August 2005 to August 2015 and underwent CRS and HIPEC. Complications are investigated from the patient's discharge date until the 90th post-operative day, and are categorized with the Clavien-Dindo classification. RESULTS: We identified 17 patients (7.8%) who developed late complications. No major differences in patient characteristics were identified between this group of 17 patients and the rest, apart from a slightly higher PCI (23.5 vs. 22.3). Mean length of stay at the re-admission was 11.7 days. 5 of the patients (29.4%) had to be re-operated on, whereas we found a mortality of 11.8% (2/17 patients). The most common complications involved abdominal abscesses (17.6%), ureteral strictures (17.6%) and enterocutaneous fistulae (17.6%). CONCLUSION: Our study highlights the late complications following CRS plus HIPEC procedures, that occur after the patient's discharge from the hospital, an issue that has not been investigated thoroughly yet and may have serious impact on the post-operative quality of life. The role of adjuvant chemotherapy following CRS and HIPEC procedures in the onset of such complications appears to be important and needs further investigation. PMID- 27385297 TI - Post-Chernobyl incidence of papillary thyroid cancer among Belgian children less than 15 years of age in April 1986: a 30-year surgical experience. AB - OBJECTIVE: We raised the question of a possible relationship in Belgium between the occurrence of papillary thyroid carcinoma (PTC) and age of children (<15 years) at the time of the Chernobyl nuclear plant accident in April 1986. SETTING: Referral university centre for endocrine surgery. MATERIAL AND METHODS: Thirty-year prospective study of the experience of a surgical team with PTC since the Chernobyl accident, taken out of 2349 patients operated on for any thyroid lesions from April 1986 to April 2015, comparing the incidence of PTC by age groups. MAIN OUTCOME MEASUREMENT: Comparison of PTC incidence in patients >15 years (group A) and children <15 years (group B) in April 1986. RESULTS: Out of a total of 2349 patients having undergone thyroid surgery for all types of lesions during 30 year after Chernobyl and born before April 1986, 2164 were >15 years of age at the time of the nuclear accident (group A) and 175 developed PTC (8.1%) compared to 36 PTC (19.5%) that occurred in 185 children <15 years of age (group B) in April 1986 (p < 0.001). CONCLUSIONS: Radiation exposure affected residents of countries (including Belgium) well beyond Ukraine and Belarus. This was demonstrated by a 1990 meteorological report. Over 30 years, there has been a persistent higher incidence of PTC among Belgian children below the age of 15 years at the time of the Chernobyl accident. This relationship with age has even been strengthened by the implementation of more sophisticated immunohistochemical biomarkers diagnostic technology since April 2011. PMID- 27385298 TI - Right-sided Cockett's syndrome. AB - Background Cockett and Thomas described and named Cockett's syndrome in 1965, commonly referred to as iliac vein compression syndrome (IVCS). It is often found as underlying cause in iliofemoral deep venous thrombosis (DVT). They described the syndrome mostly seen on the left side and predominantly in women during the second to the fourth decade of life. In this article, we present a patient with a Cockett's syndrome on the right side. Case presentation Our patient is a 52-year old female with edema of the right leg since 4 months. She had no signs of a DVT and did not benefit from a 3-month compression therapy. She was diagnosed using a CT-scan. Endovascular treatment was performed with a venous stent in the right common iliac vein (CIV). No postoperative complications were seen. After a 6 month follow-up, patient was free of pain and had no residual edema of the right leg. Conclusions Our patient presented with a non-complicated right-sided Cockett's syndrome. She was successfully treated with balloon dilatation and additional stenting of the right common iliac vein. Because of the clinical improvement of the patient together with the excellent long-term results and good patency results of the stenting, guidelines nowadays advise more and more venous stenting to prevent DVT and to relieve symptoms in case of vein compression syndromes. PMID- 27385299 TI - Three cases of triple A syndrome (Allgrove syndrome) in pediatric surgeons' view. AB - Triple A syndrome, also known as Allgrove syndrome, is a rare disease, and presents mainly in children. Its cardinal symptoms are achalasia, alacrima, and adrenocorticotropic hormone (ACTH) insensitivity. We report three cases of Triple A syndrome. Our aim is to inform pediatric surgeons about the existence of this rare syndrome and to highlight the need for suspicion of alacrima and ACTH insensitivity in cases of pediatric achalasia. Triple A syndrome should be considered in patients presenting with achalasia. Alacrima should be investigated by a Schirmer test, and adrenal dysfunction should be tested in cases of suspected triple A. PMID- 27385300 TI - Liposarcoma scroti: a rare paratesticular tumor. AB - Paratesticular liposarcoma is a rare condition characterized by a growing, painless inguinal, or scrotal mass. To our knowledge, less than 200 cases worldwide are reported thus far. It is characterized by slow growth and can reach large dimensions at diagnosis. Paratesticular well-differentiated liposarcoma has a prolonged clinical course with recurrences in more than half the cases, sometimes late. Regardless of tumor size, radical orchidectomy with free surgical margins is recommended in order to avoid recurrence. When there is tumor recurrence, reoperation is the treatment of choice because radio- and chemotherapy have yet to be well established in these cases. There is a low risk of metastasis. Overall prognosis is good. Adjuvant therapies, represented by radio- and chemotherapy, have a controversial role in the literature due to the rarity of the disease. In this article, we present review of the literature and case discussion of paratesticular liposarcoma with focus on diagnosis, treatment and follow-up. PMID- 27385301 TI - Andreas Vesalius on the anatomy and function of the lower thoracic vertebrae. AB - Some remarkable statements made by Andreas Vesalius (1514-1564) in his principal work De Humani Corporis Fabrica (1543) about the anatomy and function of the lower thoracic vertebrae are discussed in the light of information from the literature. Their accuracy is evaluated on the basis of several pieces of anatomical evidence and clinical cases. PMID- 27385302 TI - Surgery for cochlear and other auditory implants. PMID- 27385303 TI - AOSpine masters series, volume 4: adult spinal deformities. PMID- 27385305 TI - Association Between Changes in Coronary Artery Disease Progression and Treatment With Biologic Agents for Severe Psoriasis. AB - Importance: Inflammatory pathways of psoriasis share similarities with the mechanisms identified in atherosclerosis, and the association between psoriasis and cardiovascular disease due to accelerated coronary artery disease is well established. The effect of anti-inflammatory drugs on the development of coronary atherosclerosis remains essentially unknown. Objective: To investigate the association of biological therapy with changes in coronary artery disease progression, measured by repeated coronary computed tomography (CT). Design, Setting, and Participants: This single-center prospective, controlled, observer blinded clinical study at a tertiary dermatology university hospital clinic enrolled patients with severe psoriasis initiating biological therapy and matched controls not receiving systemic therapy from April 11, 2011, through June 30, 2014. Interventions: Biological therapy approved for psoriasis (adalimumab, etanercept, infliximab, ustekinumab) with the possibility to switch between treatments to ensure tight control of inflammation. Main Outcomes and Measures: Patients underwent noncontrast coronary artery calcium (CAC) CT and contrast enhanced coronary CT angiography at baseline and after 13 months of follow-up. Changes in CAC score, number of coronary plaques, severity of narrowing, composition, and vessel wall volume were measured. Results: There were 28 treated patients (mean [SD] age, 49.2 [10.2] years; 71% men; mean [SD] Psoriasis Area Severity Index [PASI], 15.4 [4.3]) and 28 controls (mean [SD] age, 52.8 [10.6] years; 71% men; mean [SD] PASI, 12.4 [3.9]). The CAC scores remained stable in the intervention group (mean [SD] yearly CAC change, -16 [56]; P = .15) and progressed in the control group (14 [29]; P = .02) (intervention vs controls: P = .02). The number of segments with luminal abnormalities remained unchanged in both groups. The severity of luminal narrowing in the diseased segments was unchanged in the intervention group (Wilcoxon W = 76, n = 483, P = .39) but increased at follow-up in the control group (Wilcoxon W = 281, n = 414, P = .02). Automated vessel wall volume index remained unchanged from baseline to follow-up in the intervention group (mean [SD] baseline, 7.1 [1.5], follow-up, 7.1 [1.7]; P = .91), while controls demonstrated statistically nonsignificant progression (baseline, 8.3 [1.6], follow-up, 8.9 [2.2]; P = .06). Conclusions and Relevance: Clinically effective treatment with biologic agents was associated with reduced coronary artery disease progression in patients with severe psoriasis. These findings support a beneficial effect of biologic anti-inflammatory agents in preventing cardiovascular disease progression in addition to disease control in inflammatory diseases. PMID- 27385304 TI - White spot syndrome virus entry is dependent on multiple endocytic routes and strongly facilitated by Cq-GABARAP in a CME-dependent manner. AB - White spot syndrome virus (WSSV) is a lethal pathogen of shrimp and many other crustaceans, including crayfish. However, the molecular mechanism underlying its cellular entry remains elusive due to the lack of shrimp cell lines for viral propagation. Crayfish hematopoietic tissue (Hpt) cell culture was recently established as a good model for WSSV infection study. Here, we showed that multiple endocytic routes, including clathrin-mediated endocytosis (CME), macropinocytosis and caveolae-mediated endocytosis, were indispensably employed for the viral entry into Hpt cell of the crayfish Cherax quadricarinatus. Intriguingly, cellular autophagic activity was positively correlated with efficient viral entry, in which a key autophagy-related protein, gamma aminobutyric acid receptor-associated protein (Cq-GABARAP), that not only localized but also co-localized with WSSV on the Hpt cell membrane, strongly facilitated WSSV entry by binding to the viral envelope VP28 in a CME-dependent manner that was negatively regulated by Cq-Rac1. Furthermore, cytoskeletal components, including Cq-beta-tubulin and Cq-beta-actin, bound to both recombinant rCq-GABARAP and WSSV envelope proteins, which likely led to viral entry promotion via cooperation with rCq-GABARAP. Even under conditions that promoted viral entry, rCq-GABARAP significantly reduced viral replication at an early stage of infection, which was probably caused by the formation of WSSV aggregates in the cytoplasm. PMID- 27385306 TI - Reply to "Standardizing Biparametric MRI to Simplify and Improve Prostate Imaging Reporting and Data System, Version 2, in Prostate Cancer Management". PMID- 27385308 TI - Long Residence Time at the Neurosteroidogenic 18 kDa Translocator Protein Characterizes the Anxiolytic Ligand XBD173. AB - Recent data have demonstrated a positive correlation between the residence time (RT) and neurosteroidogenic efficacy of a ligand at the translocator protein (TSPO), an attractive anxyolitic target. To explore the potential impact of RT on TSPO ligand anxiolytic activity, the RT and the steroidogenic activity of XBD173, a ligand exerting anxiolytic activity in humans, were retrospectively evaluated. To this aim, XBD173 association and dissociation rate constants were measured (1.23 * 10(7) M(-1) min(-1) and 0.0079 min(-1), respectively). XBD173 resulted to have a long RT (127 min) and to stimulate efficaciously neurosteroidogenesis, in terms of pregnenolone production. The present findings corroborate the importance of TSPO ligand RT to predict their effective neurosteroidogenic activity and promising anxiolytic action. These positive results prompted us to set up a fast and high-throughput kinetic method to improve the efficiency of RT-based TSPO drug-discovery process. PMID- 27385307 TI - Syndesome Therapeutics for Enhancing Diabetic Wound Healing. AB - Chronic wounds represent a major healthcare and economic problem worldwide. Advanced wound dressings that incorporate bioactive compounds have great potential for improving outcomes in patients with chronic wounds but significant challenges in designing treatments that are effective in long-standing, nonhealing wounds. Here, an optimized wound healing gel was developed that delivers syndecan-4 proteoliposomes ("syndesomes") with fibroblast growth factor 2 (FGF-2) to enhance diabetic wound healing. In vitro studies demonstrate that syndesomes markedly increase migration of keratinocytes and fibroblasts isolated from both nondiabetic and diabetic donors. In addition, syndesome treatment leads to increased endocytic processing of FGF-2 that includes enhanced recycling of FGF-2 to the cell surface after uptake. The optimized syndesome formulation was incorporated into an alginate wound dressing and tested in a splinted wound model in diabetic, ob/ob mice. It was found that wounds treated with syndesomes and FGF 2 have markedly enhanced wound closure in comparison to wounds treated with only FGF-2. Moreover, syndesomes have an immunomodulatory effect on wound macrophages, leading to a shift toward the M2 macrophage phenotype and alterations in the wound cytokine profile. Together, these studies show that delivery of exogenous syndecan-4 is an effective method for enhancing wound healing in the long-term diabetic diseased state. PMID- 27385309 TI - Relationship between Community Drug Administration Strategy and Changes in Trachoma Prevalence, 2007 to 2013. AB - BACKGROUND: Australia is the only high income country with persisting endemic trachoma. A national control program involving mass drug administration with oral azithromycin, in place since 2006, has some characteristics which differ from programs in low income settings, particularly in regard to the use of a wider range of treatment strategies, and more regular assessments of community prevalence. We aimed to examine the association between treatment strategies and trachoma prevalence. METHODS: Through the national surveillance program, annual data from 2007-2013 were collected on trachoma prevalence and treatment with oral azithromycin in children aged 5-9 years from three Australian regions with endemic trachoma. Communities were classified for each year according to one of four trachoma treatment strategies implemented (no treatment, active cases only, household and community-wide). We estimated the change in trachoma prevalence between sequential pairs of years and across multiple years according to treatment strategy using random-effects meta-analyses. FINDINGS: Over the study period, 182 unique remote Aboriginal communities had 881 annual records of both trachoma prevalence and treatment. From the analysis of pairs of years, the greatest annual fall in trachoma prevalence was in communities implementing community-wide strategies, with yearly absolute reductions ranging from -8% (95%CI -17% to 1%) to -31% (-26% to -37%); these communities also had the highest baseline trachoma prevalence (15.4%-43.9%). Restricting analyses to communities with moderate trachoma prevalence (5-19%) at initial measurement, and comparing community trachoma prevalence from the first to the last year of available data for the community, both community-wide and more targeted treatment strategies were associated with similar absolute reductions (-11% [-8% to -13%] and -7% [-5% to -10%] respectively). Results were similar stratified by region. INTERPRETATION: Consistent with previous research, community-wide administration of azithromycin reduces trachoma prevalence. Our observation that less intensive treatment with a 'household' strategy in moderate prevalence communities (5-<20%) is associated with similar reductions in prevalence over time, will require confirmation in other settings if it is to be used as a basis for changes in control strategies. PMID- 27385310 TI - [Rectal mucosa metastasis in recurrent prostate cancer : (68)Ga-PSMA-PET/CT allows targeted salvage radiotherapy]. AB - This article presents for the first time a case of rectal mucosa metastasis of recurrent prostate cancer that was diagnosed with (68)Ga-PSMA PET/CT. After histological confirmation, the patient was treated with salvage radiotherapy. This case report underlines the specificity and efficacy of PSMA-based PET imaging. In case of biochemical relapse, it can be used even at low PSA levels to detect prostate cancer metastases that might also be in atypical locations. Thus, (68)Ga-PSMA PET/CT may allow new options for salvage therapy. PMID- 27385311 TI - [Residents' schedule for the Congress of the German Society for Urology 2016]. PMID- 27385312 TI - [Pharmacological treatments for fatigue associated with palliative care]. PMID- 27385313 TI - [Delegation of urological services]. PMID- 27385314 TI - Controlling Regiochemistry in the Syntheses of Boraindanes from Diborane(4) Starting Materials. AB - The reaction of tert-butylisonitrile (tBuNC) with 1,2-dihalo-1,2-diduryldiborane leads initially to the formation of the mono-base adduct of the symmetrical diborane(4), which then undergoes an intramolecular cyclization resulting in the formation of a 1-boraindane. This result is in contrast to a previously reported cyclization of a mono-isonitrile adduct of an unsymmetrical 1,1-pinacol-2,2 diaryldiborane(4), which results in the formation of a 1-boraindane. This latter result is herein confirmed by the reaction of 1,1-difluoro-2,2 dimesityldiborane(4) with tBuNC, which yielded the 2-boraindane compound. The mechanism of the former reaction has been computationally elucidated, and the differences between this route and the pathway to 1-boraindanes is discussed. These reactions further the understanding of the chemistry of the increasingly popular mono-base adducts of diborane(4), demonstrate the versatility of isonitriles in comparison to standard two-electron donors, and elucidate selective routes to boron-containing polycyclics, such as those being proposed as analogues for conventional organic pharmaceuticals. PMID- 27385315 TI - Weight and prognosis for influenza A(H1N1)pdm09 infection during the pandemic period between 2009 and 2011: a systematic review of observational studies with meta-analysis. AB - BACKGROUND: In 2009, a novel influenza A(H1N1)pdm09 virus was detected and caused influenza pandemic. It is important to identify the risk factors for severe outcomes. However, inconsistent results regarding the effect of obesity were reported in previous studies. METHODS: We conducted a systematic review to assess the association between obesity and poor prognosis for laboratory-confirmed A(H1N1)pdm09 influenza. We searched three English databases and three Chinese databases for relevant studies from April 2009 to October 2015: PubMed, the Cochrane library, Embase, CNKI, CBM, and Wanfang. Two investigators independently identified eligible articles, assessed quality using NOS, and extracted data. We performed meta-analyses and meta-regressions to estimate the association between weight and poor prognosis for influenza A(H1N1)pdm09 infection, when data were available. RESULTS: We identified 22 articles enrolling 25,189 laboratory confirmed patients. The pooled estimates indicated obesity significantly increased the risk of fatal and critical complications of influenza A(H1N1)pdm09 infection (for fatal, OR = 1.81, 95% CI: 1.23-2.65; for critical complications, OR = 1.67, 95% CI: 1.13-2.47). However, we found significant interaction between early antiviral treatment and obesity (beta = -0.28). After adjustment for early antiviral treatment, relationship between obesity and poor outcomes disappeared (OR = 1.14, 95% CI: 0.94-1.39). CONCLUSIONS: The results of the meta-analyses showed obesity significantly increased the risk of death, critical complications, and severe complications for influenza A(H1N1)pdm09 infection, especially among high-quality studies and in Asia region. Importantly, the result from our meta regression indicated that the conclusion should be interpreted with caution, because early antiviral treatment might be a key confounding factor. PMID- 27385316 TI - Factors influencing the ablative efficiency of high intensity focused ultrasound (HIFU) treatment for adenomyosis: A retrospective study. AB - Objectives The aim of this study was to investigate factors affecting ablative efficiency of high intensity focused ultrasound (HIFU) for adenomyosis. Materials and methods In all, 245 patients with adenomyosis who underwent ultrasound guided HIFU (USgHIFU) were retrospectively reviewed. All patients underwent dynamic contrast-enhanced magnetic resonance imaging (MRI) before and after HIFU treatment. The non-perfused volume (NPV) ratio, energy efficiency factor (EEF) and greyscale change were set as dependent variables, while the factors possibly affecting ablation efficiency were set as independent variables. These variables were used to build multiple regression models. Results A total of 245 patients with adenomyosis successfully completed HIFU treatment. Enhancement type on T1 weighted image (WI), abdominal wall thickness, volume of adenomyotic lesion, the number of hyperintense points, location of the uterus, and location of adenomyosis all had a linear relationship with the NPV ratio. Distance from skin to the adenomyotic lesion's ventral side, enhancement type on T1WI, volume of adenomyotic lesion, abdominal wall thickness, and signal intensity on T2WI all had a linear relationship with EEF. Location of the uterus and abdominal wall thickness also both had a linear relationship with greyscale change. Conclusion The enhancement type on T1WI, signal intensity on T2WI, volume of adenomyosis, location of the uterus and adenomyosis, number of hyperintense points, abdominal wall thickness, and distance from the skin to the adenomyotic lesion's ventral side can all be used as predictors of HIFU for adenomyosis. PMID- 27385317 TI - Bacterial meningitis in solid organ transplant recipients: a population-based prospective study. AB - BACKGROUND: Solid organ transplant (SOT) recipients are at risk of infections of the central nervous system. However, the incidence and clinical course of bacterial meningitis in SOT recipients are unclear. We studied occurrence, disease course, and prognosis of bacterial meningitis in SOT recipients in the Netherlands. METHODS: All patients with a medical history of solid organ transplantation were selected from our nationwide prospective cohort study on community-acquired bacterial meningitis in patients >16 years old, performed from March 1, 2006 to October 31, 2014. Data on patient history, symptoms and signs on admission, treatment, and outcome were collected prospectively. For transplant recipients, additional information was collected retrospectively. RESULTS: We identified 6 SOT recipients, all receiving renal transplants. The annual incidence of bacterial meningitis was 7-fold higher (95% confidence interval [CI] 2.94-17.02, P < 0.001) for renal transplant recipients as compared with the general population (9.56 [95% CI 3.98-22.96] vs. 1.35 [95% CI 1.28-1.43] per 100,000 patients per year). One of the 6 patients (17%) presented with the classic presentation of bacterial meningitis (fever, neck stiffness, and change in mental status). Seizures were common, occurring in 33% of patients. Streptococcus pneumoniae and Listeria monocytogenes were identified in 2 patients each, and Escherichia coli and Pseudomonas aeruginosa were both identified once. Four of 6 patients (67%) had an unfavorable functional outcome. CONCLUSION: Bacterial meningitis is a rare but devastating complication of solid organ transplantation. SOT recipients are at high risk for developing meningitis, and recognition of this condition may be difficult, owing to atypical clinical manifestation. PMID- 27385318 TI - Identification of matrix metalloproteinase-12 as a candidate molecule for prevention and treatment of cardiometabolic disease. AB - Obesity is strongly associated with metabolic syndrome, a combination of risk factors that predispose to the development of the cardiometabolic diseases: atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Prevention of metabolic syndrome requires novel interventions to address this health challenge. The objective of this study was the identification of candidate molecules for the prevention and treatment of insulin resistance and atherosclerosis, conditions that underlie type 2 diabetes mellitus and cardiovascular disease, respectively. We used an unbiased bioinformatics approach to identify molecules that are upregulated in both conditions by combining murine and human data from a microarray experiment and meta-analyses. We obtained a pool of eight genes that were upregulated in all the databases analysed. This included well known and novel molecules involved in the pathophysiology of type 2 diabetes mellitus and cardiovascular disease. Notably, matrix metalloproteinase 12 (MMP12) was highly ranked in all analyses and was therefore chosen for further investigation. Analyses of visceral and subcutaneous white adipose tissue from obese compared to lean mice and humans convincingly confirmed the up-regulation of MMP12 in obesity at mRNA, protein and activity levels. In conclusion, using this unbiased approach an interesting pool of candidate molecules was identified, all of which have potential as targets in the treatment and prevention of cardiometabolic diseases. PMID- 27385319 TI - [Voiding disorders in geriatric patients : Correlation with age-related functional impairments]. AB - INTRODUCTION: Voiding disorders are a common problem in elderly people. The highest incidence and prevalence occurs in female patients with a high level of dependency and cognitive impairments. AIM: The aim of the study was to define the correlation between the presence of voiding disorders and age-related functional deficits in hospitalized elderly patients within the framework of a comprehensive geriatric assessment. This is of utmost importance for planning adequate further diagnostic and therapeutic measures. METHODS: This study involved a retrospective cross-sectional assessment of data from 7487 hospitalized patients (74.1 % females, 25.9 % males, mean age 78.9 +/- 7.2 years) evaluated by a multidimensional geriatric assessment. Items tested were symptoms of voiding disorders, activities of daily living, cognitive and emotional status, mobility, handgrip strength, need for walking aids, pain, nutritional status and visual function. Data were evaluated with respect to the prevalence of voiding disorders, patient functional status and to the relationship between these findings. RESULTS: Among all patients 4494 (60.0 %) presented with voiding disorders. Of these 95.8 % showed additional relevant functional deficits in three or more test items. Voiding disorders were positively correlated to patient age, dependency in activities of daily living and pain scores and were negatively correlated to cognitive and emotional status, mobility, hand grip strength, nutritional status and visual function. The functional deficits were associated with the severity of voiding disorders. Female patients were more often affected by voiding disorders as well as by functional impairments in comparison to male patients. DISCUSSION: The results showed that more than half of the elderly hospitalized patients suffered from voiding disorders. The high prevalence and correlation between the presence of voiding disorders and functional deficits indicate the need to clearly define and plan diagnostic and therapeutic measures (e. g. bladder diaries and bladder retraining) for these patients, taking the individual functional status into consideration. CONCLUSION: In older patients with voiding disorders, high levels of functional impairment should be considered before planning diagnostic and therapeutic measures in order to ensure the quality of implementation. PMID- 27385320 TI - Water of Hydration Dynamics in Minerals Gypsum and Bassanite: Ultrafast 2D IR Spectroscopy of Rocks. AB - Water of hydration plays an important role in minerals, determining their crystal structures and physical properties. Here ultrafast nonlinear infrared (IR) techniques, two-dimensional infrared (2D IR) and polarization selective pump probe (PSPP) spectroscopies, were used to measure the dynamics and disorder of water of hydration in two minerals, gypsum (CaSO4.2H2O) and bassanite (CaSO4.0.5H2O). 2D IR spectra revealed that water arrangement in freshly precipitated gypsum contained a small amount of inhomogeneity. Following annealing at 348 K, water molecules became highly ordered; the 2D IR spectrum became homogeneously broadened (motional narrowed). PSPP measurements observed only inertial orientational relaxation. In contrast, water in bassanite's tubular channels is dynamically disordered. 2D IR spectra showed a significant amount of inhomogeneous broadening caused by a range of water configurations. At 298 K, water dynamics cause spectral diffusion that sampled a portion of the inhomogeneous line width on the time scale of ~30 ps, while the rest of inhomogeneity is static on the time scale of the measurements. At higher temperature, the dynamics become faster. Spectral diffusion accelerates, and a portion of the lower temperature spectral diffusion became motionally narrowed. At sufficiently high temperature, all of the dynamics that produced spectral diffusion at lower temperatures became motionally narrowed, and only homogeneous broadening and static inhomogeneity were observed. Water angular motions in bassanite exhibit temperature-dependent diffusive orientational relaxation in a restricted cone of angles. The experiments were made possible by eliminating the vast amount of scattered light produced by the granulated powder samples using phase cycling methods. PMID- 27385321 TI - Morpho-colorimetric characterisation of Malva alliance taxa by seed image analysis. AB - Seed morphometric and -colorimetric features describing shape, size and textural seed traits of 28 taxa belonging to the genera Lavatera L. and Malva L., were recorded by means of computer vision techniques. The data were statistically analysed to contribute to the taxonomical treatment of the Malva alliance and to assess some doubtful systematic positions. A clear differentiation between taxa traditionally attributed to Lavatera or Malva was highlighted. Furthermore, the identification system proposed here was able to discriminate among the Lavatera sections, confirming the taxonomic organization of this genus. The results obtained for Malva, both at the species level and among sections, supported this analytical tool as diagnostic for systematic purposes. PMID- 27385323 TI - Interfacial strain and defects in asymmetric Fe-Mn oxide hybrid nanoparticles. AB - Asymmetric Fe-Mn oxide hybrid nanoparticles have been obtained by a seed-mediated thermal decomposition-based synthesis route. The use of benzyl ether as the solvent was found to promote the orientational growth of Mn1-xO onto the iron oxide nanocube seeds yielding mainly dimers and trimers whereas 1-octadecene yields large nanoparticles. HRTEM imaging and HAADF-STEM tomography performed on dimers show that the growth of Mn1-xO occurs preferentially along the edges of iron oxide nanocubes where both oxides share a common crystallographic orientation. Fourier filtering and geometric phase analysis of dimers reveal a lattice mismatch of 5% and a large interfacial strain together with a significant concentration of defects. The saturation magnetization is lower and the coercivity is higher for the Fe-Mn oxide hybrid nanoparticles compared to the iron oxide nanocube seeds. PMID- 27385322 TI - Development of pristane induced mice model for lupus with atherosclerosis and analysis of TLR expression. AB - OBJECTIVES: This study was designed to establish a murine model of lupus with atherosclerosis, and to investigate the expression of Toll-like receptors (TLRs) in the aorta and kidney. METHODS: The 9-week-old female ApoE-/- and C57BL/6 mice were randomly divided into a ApoE-/- pristane treated group (group A), ApoE-/- control group (group B), C57BL/6 pristane treated group (group C) and C57BL/6 control group (group D). Each mouse was given either a single intraperitoneal injection of 0.5 ml pristane or saline. RESULTS: We observed that group A mice specifically had poor spirit, less activity, obvious hair loss, splenomegalia and renomegaly. Levels of ANA, anti-ds-DNA and anti-Sm antibodies were significantly higher than those in other groups. The group A and B mice generally displayed intimal hyperplasia and atherosclerosis mottling in the lumen of the aorta. The kidney tissues from group A, B and C mice showed increased expression levels of TLR2, TLR4, TLR7 and TLR9 proteins in comparison to group D. However, Group A mice did not show any significant difference in TLR2 and TLR4 protein expression levels when compared to group B and C, but displayed higher TLR7 expression than group B and higher TLR9 expression than group B and C mice. In contrast, the group A and B mice apparently expressed TLR2 and TLR4. CONCLUSIONS: We concluded that pristane treated apoE-/- mice exhibited lupus-like phenotype and developed atherosclerosis. The pristane treatment also induced abnormally high expression of TLR2 and TLR4 in the aorta and TLR2, TLR4, TLR7 and TLR9 in the kidney of apoE /- mice. PMID- 27385324 TI - Excited-State Dipole and Quadrupole Moments: TD-DFT versus CC2. AB - The accuracies of the excited-state dipole and quadrupole moments obtained by TD DFT are assessed by considering 16 different exchange-correlation functionals and more than 30 medium and large molecules. Except for excited-state presenting a significant charge-transfer character, a relatively limited dependency on the nature of the functional is found. It also turns out that while DFT ground-state dipole moments tend to be too large, the reverse trend is obtained for their excited-state counterparts, at least when hybrid functionals are used. Consequently, the TD-DFT excess dipole moments are often too small, an error that can be fortuitously corrected for charge-transfer transition by selecting a pure or a hybrid functional containing a small share of exact exchange. This error cancelation phenomena explains the contradictory conclusions obtained in previous investigations. Overall, the largest correlation between CC2 and TD-DFT excess dipoles is obtained with M06-2X, but at the price of a nearly systematic underestimation of this property by ca. 1 D. For the excess quadrupole moments, the average errors are of the order of 0.2-0.6 D.A for the set of small aromatic systems treated. PMID- 27385325 TI - Completely independent electrical control of spin and valley in a silicene field effect transistor. AB - One-atom-thick silicene is a silicon-based hexagonal-lattice material with buckled structure, where an electron fuses multiple degrees of freedom including spin, sublattice pseudospin and valley. We here demonstrate that a valley selective spin filter (VSSF) that supports single-valley and single-spin transport can be realized in a silicene field effect transistor constructed of an npn junction, where an antiferromagnetic exchange field and a perpendicular electric field are applied in the p-doped region. The nontrivial VSSF property benefits from an electrically controllable state of spin-polarized single-valley Dirac cone. By reversing the electric field direction, the device can operate as a spin-reversed but valley-unreversed filter due to the dependence of band gap on spin and valley. Further, we find that all the possible spin-valley configurations of VSSF can be achieved just by tuning the electric field. Our findings pave the way to the realization of completely independent electrical control of spin and valley in silicene circuits. PMID- 27385326 TI - Five minutes with . . . David Gilbert, patient director. PMID- 27385327 TI - Elevations in the Fasting Serum Proinsulin-to-C-Peptide Ratio Precede the Onset of Type 1 Diabetes. AB - OBJECTIVE: We tested whether an elevation in the serum proinsulin-to-C-peptide ratio (PI:C), a biomarker of beta-cell endoplasmic reticulum (ER) dysfunction, was associated with progression to type 1 diabetes. RESEARCH DESIGN AND METHODS: Fasting total PI and C levels were measured in banked serum samples obtained from TrialNet Pathway to Prevention (PTP) participants, a cohort of autoantibody positive relatives without diabetes of individuals with type 1 diabetes. Samples were obtained ~12 months before diabetes onset from PTP progressors in whom diabetes developed (n = 60), and were compared with age-, sex-, and BMI-matched nonprogressors who remained normoglycemic (n = 58). PI:C ratios were calculated as molar ratios and were multiplied by 100% to obtain PI levels as a percentage of C levels. RESULTS: Although absolute PI levels did not differ between groups, PI:C ratios were significantly increased in antibody-positive subjects in whom there was progression to diabetes compared with nonprogressors (median 1.81% vs. 1.17%, P = 0.03). The difference between groups was most pronounced in subjects who were <=10 years old, where the median progressor PI:C ratio was nearly triple that of nonprogressors; 90.0% of subjects in this age group within the upper PI:C quartile progressed to the development of diabetes. Logistic regression analysis, adjusted for age and BMI, demonstrated increased odds of progression for higher natural log PI:C ratio values (odds ratio 1.44, 95% CI 1.02, 2.05). CONCLUSIONS: These data suggest that beta-cell ER dysfunction precedes type 1 diabetes onset, especially in younger children. Elevations in the serum PI:C ratio may have utility in predicting the onset of type 1 diabetes in the presymptomatic phase. PMID- 27385328 TI - Association Between Diabetes and Hippocampal Atrophy in Elderly Japanese: The Hisayama Study. AB - OBJECTIVE: To investigate the association between diabetes and brain or hippocampal atrophy in an elderly population. RESEARCH DESIGN AND METHODS: A total of 1,238 community-dwelling Japanese subjects aged >=65 years underwent brain MRI scans and a comprehensive health examination in 2012. Total brain volume (TBV), intracranial volume (ICV), and hippocampal volume (HV) were measured using MRI scans for each subject. We examined the associations between diabetes-related parameters and the ratios of TBV to ICV (an indicator of global brain atrophy), HV to ICV (an indicator of hippocampal atrophy), and HV to TBV (an indicator of hippocampal atrophy beyond global brain atrophy) after adjustment for other potential confounders. RESULTS: The multivariable-adjusted mean values of the TBV-to-ICV, HV-to-ICV, and HV-to-TBV ratios were significantly lower in the subjects with diabetes compared with those without diabetes (77.6% vs. 78.2% for the TBV-to-ICV ratio, 0.513% vs. 0.529% for the HV-to-ICV ratio, and 0.660% vs. 0.676% for the HV-to-TBV ratio; all P < 0.01). These three ratios decreased significantly with elevated 2-h postload glucose (PG) levels (all P for trend <0.05) but not fasting plasma glucose levels. Longer duration of diabetes was significantly associated with lower TBV-to-ICV, HV-to-ICV, and HV-to-TBV ratios. The subjects with diabetes diagnosed in midlife had significantly lower HV-to-ICV and HV-to-TBV ratios than those without and those diagnosed in late life. CONCLUSIONS: Our data suggest that a longer duration of diabetes and elevated 2-h PG levels, a marker of postprandial hyperglycemia, are risk factors for brain atrophy, particularly hippocampal atrophy. PMID- 27385329 TI - A Population-Based Study of All-Cause Mortality and Cardiovascular Disease in Association With Prior History of Hypoglycemia Among Patients With Type 1 Diabetes. AB - OBJECTIVE: This study investigated the effects of severe hypoglycemia on risks of all-cause mortality and cardiovascular disease (CVD) incidence in patients with type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS: Two nested case control studies with age- and sex-matched control subjects and using the time density sampling method were performed separately within a cohort of 10,411 patients with T1DM in Taiwan. The study enrolled 564 nonsurvivors and 1,615 control subjects as well as 743 CVD case subjects and 1,439 control subjects between 1997 and 2011. History of severe hypoglycemia was identified during 1 year, 1-3 years, and 3-5 years before the occurrence of the study outcomes. Conditional logistic regression analyses were performed to estimate the odds ratio (OR) and 95% CI of the study outcomes. RESULTS: Prior severe hypoglycemic events within 1 year were associated with higher risks of all-cause mortality and CVD (adjusted OR 2.74 [95% CI 1.96-3.85] and 2.02 [1.35-3.01], respectively). Events occurring within 1-3 years and 3-5 years before death were also associated with adjusted ORs of 1.94 (95% CI 1.39-2.71) and 1.68 (1.15-2.44), respectively. Significant dose-gradient effects of severe hypoglycemia frequency on mortality and CVD were observed within 5 years. CONCLUSIONS: Although the CVD incidence may be associated with severe hypoglycemic events occurring in the previous year, the risk of all-cause mortality was associated with severe hypoglycemic events occurring in the preceding 5 years. Exposure to repeated severe hypoglycemic events can lead to higher risks of mortality and CVD. PMID- 27385330 TI - Secreted Frizzled-Related Protein 4 (SFRP4): A Novel Biomarker of beta-Cell Dysfunction and Insulin Resistance in Individuals With Prediabetes and Type 2 Diabetes. PMID- 27385331 TI - A close examination of the structure and dynamics of HC(NH2)2PbI3 by MD simulations and group theory. AB - The formamidinium lead iodide hybrid perovskite is studied using first principles molecular dynamics simulations and further analyzed using group theory. The simulations are performed on large supercells containing 768 atoms under isothermal and fully anisotropic isobaric conditions. Two trajectories, one at 300 K and another at 450 K, were extended for over 50 ps in order to perform a detailed assessment of the rotational dynamics of organic cations. The characteristic rotations of the cation are analyzed by defining two rotation axes. It is found that the formamidinium molecules rotate preferentially around the direction parallel to the line connecting the two nitrogen atoms. The rotational dynamics shows some characteristics already observed in methylammonium lead iodide, like the heterogeneous dynamics at room temperature that disappears at 450 K. The orientational probability of the molecules is explored in terms of an expansion in cubic harmonics up to the 12th order. It reveals a strong directionality at room temperature that relaxes when increasing the temperature. These findings are further rationalized using Landau and group theories suggesting a mixed displacive/order-disorder structural instability at lower temperatures. PMID- 27385332 TI - Comparative assessment of fluorescent proteins for in vivo imaging in an animal model system. AB - Fluorescent protein tags are fundamental tools used to visualize gene products and analyze their dynamics in vivo. Recent advances in genome editing have expedited the precise insertion of fluorescent protein tags into the genomes of diverse organisms. These advances expand the potential of in vivo imaging experiments and facilitate experimentation with new, bright, photostable fluorescent proteins. Most quantitative comparisons of the brightness and photostability of different fluorescent proteins have been made in vitro, removed from biological variables that govern their performance in cells or organisms. To address the gap, we quantitatively assessed fluorescent protein properties in vivo in an animal model system. We generated transgenic Caenorhabditis elegans strains expressing green, yellow, or red fluorescent proteins in embryos and imaged embryos expressing different fluorescent proteins under the same conditions for direct comparison. We found that mNeonGreen was not as bright in vivo as predicted based on in vitro data but is a better tag than GFP for specific kinds of experiments, and we report on optimal red fluorescent proteins. These results identify ideal fluorescent proteins for imaging in vivo in C. elegans embryos and suggest good candidate fluorescent proteins to test in other animal model systems for in vivo imaging experiments. PMID- 27385333 TI - Protein kinase A can block EphA2 receptor-mediated cell repulsion by increasing EphA2 S897 phosphorylation. AB - The EphA2 receptor tyrosine kinase plays key roles in tissue homeostasis and disease processes such as cancer, pathological angiogenesis, and inflammation through two distinct signaling mechanisms. EphA2 "canonical" signaling involves ephrin-A ligand binding, tyrosine autophosphorylation, and kinase activity; EphA2 "noncanonical" signaling involves phosphorylation of serine 897 (S897) by AKT and RSK kinases. To identify small molecules counteracting EphA2 canonical signaling, we developed a high-content screening platform measuring inhibition of ephrin-A1 induced PC3 prostate cancer cell retraction. Surprisingly, most hits from a screened collection of pharmacologically active compounds are agents that elevate intracellular cAMP by activating G protein-coupled receptors such as the beta2 adrenoceptor. We found that cAMP promotes phosphorylation of S897 by protein kinase A (PKA) as well as increases the phosphorylation of several nearby serine/threonine residues, which constitute a phosphorylation hotspot. Whereas EphA2 canonical and noncanonical signaling have been viewed as mutually exclusive, we show that S897 phosphorylation by PKA can coexist with EphA2 tyrosine phosphorylation and block cell retraction induced by EphA2 kinase activity. Our findings reveal a novel paradigm in EphA2 function involving the interplay of canonical and noncanonical signaling and highlight the ability of the beta2-adrenoceptor/cAMP/PKA axis to rewire EphA2 signaling in a subset of cancer cells. PMID- 27385334 TI - Improved reconstitution of yeast vacuole fusion with physiological SNARE concentrations reveals an asymmetric Rab(GTP) requirement. AB - In vitro reconstitution of homotypic yeast vacuole fusion from purified components enables detailed study of membrane fusion mechanisms. Current reconstitutions have yet to faithfully replicate the fusion process in at least three respects: 1) The density of SNARE proteins required for fusion in vitro is substantially higher than on the organelle. 2) Substantial lysis accompanies reconstituted fusion. 3) The Rab GTPase Ypt7 is essential in vivo but often dispensable in vitro. Here we report that changes in fatty acyl chain composition dramatically lower the density of SNAREs that are required for fusion. By providing more physiological lipids with a lower phase transition temperature, we achieved efficient fusion with SNARE concentrations as low as on the native organelle. Although fused proteoliposomes became unstable at elevated SNARE concentrations, releasing their content after fusion had occurred, reconstituted proteoliposomes with substantially reduced SNARE concentrations fused without concomitant lysis. The Rab GTPase Ypt7 is essential on both membranes for proteoliposome fusion to occur at these SNARE concentrations. Strikingly, it was only critical for Ypt7 to be GTP loaded on membranes bearing the R-SNARE Nyv1, whereas the bound nucleotide of Ypt7 was irrelevant on membranes bearing the Q SNAREs Vam3 and Vti1. PMID- 27385335 TI - Detection of protein-protein interactions at the septin collar in Saccharomyces cerevisiae using a tripartite split-GFP system. AB - Various methods can provide a readout of the physical interaction between two biomolecules. A recently described tripartite split-GFP system has the potential to report by direct visualization via a fluorescence signal the intimate association of minimally tagged proteins expressed at their endogenous level in their native cellular milieu and can capture transient or weak interactions. Here we document the utility of this tripartite split-GFP system to assess in living cells protein-protein interactions in a dynamic cytoskeletal structure-the septin collar at the yeast bud neck. We show, first, that for septin-septin interactions, this method yields a robust signal whose strength reflects the known spacing between the subunits in septin filaments and thus serves as a "molecular ruler." Second, the method yields little or no spurious signal even with highly abundant cytosolic proteins readily accessible to the bud neck (including molecular chaperone Hsp82 and glycolytic enzyme Pgk1). Third, using two proteins (Bni5 and Hsl1) that have been shown by other means to bind directly to septins at the bud neck in vivo, we validate that the tripartite split-GFP method yields the same conclusions and further insights about specificity. Finally, we demonstrate the capacity of this approach to uncover additional new information by examining whether three other proteins reported to localize to the bud neck (Nis1, Bud4, and Hof1) are able to interact physically with any of the subunits in the septin collar and, if so, with which ones. PMID- 27385336 TI - AMPK activity regulates trafficking of mitochondria to the leading edge during cell migration and matrix invasion. AB - Cell migration is a complex behavior involving many energy-expensive biochemical events that iteratively alter cell shape and location. Mitochondria, the principal producers of cellular ATP, are dynamic organelles that fuse, divide, and relocate to respond to cellular metabolic demands. Using ovarian cancer cells as a model, we show that mitochondria actively infiltrate leading edge lamellipodia, thereby increasing local mitochondrial mass and relative ATP concentration and supporting a localized reversal of the Warburg shift toward aerobic glycolysis. This correlates with increased pseudopodial activity of the AMP-activated protein kinase (AMPK), a critically important cellular energy sensor and metabolic regulator. Furthermore, localized pharmacological activation of AMPK increases leading edge mitochondrial flux, ATP content, and cytoskeletal dynamics, whereas optogenetic inhibition of AMPK halts mitochondrial trafficking during both migration and the invasion of three-dimensional extracellular matrix. These observations indicate that AMPK couples local energy demands to subcellular targeting of mitochondria during cell migration and invasion. PMID- 27385338 TI - Multiple ER-Golgi SNARE transmembrane domains are dispensable for trafficking but required for SNARE recycling. AB - The formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes between opposing membranes is an essential prerequisite for fusion between vesicles and their target compartments. The composition and length of a SNARE's transmembrane domain (TMD) is also an indicator for their steady-state distribution in cells. The evolutionary conservation of the SNARE TMD, together with the strict requirement of this feature for membrane fusion in biochemical studies, implies that the TMD represents an essential protein module. Paradoxically, we find that for several essential ER- and Golgi-localized SNAREs, a TMD is unnecessary. Moreover, in the absence of a covalent membrane tether, such SNAREs can still support ER-Golgi vesicle transport and recapitulate established genetic interactions. Transport anomalies appear to be restricted to retrograde trafficking, but these defects are overcome by the attachment of a C-terminal lipid anchor to the SNARE. We conclude that the TMD functions principally to support the recycling of Qb-, Qc-, and R-SNAREs and, in so doing, retrograde transport. PMID- 27385337 TI - Roles of the novel coiled-coil protein Rng10 in septum formation during fission yeast cytokinesis. AB - Rho GAPs are important regulators of Rho GTPases, which are involved in various steps of cytokinesis and other processes. However, regulation of Rho-GAP cellular localization and function is not fully understood. Here we report the characterization of a novel coiled-coil protein Rng10 and its relationship with the Rho-GAP Rga7 in fission yeast. Both rng10Delta and rga7Delta result in defective septum and cell lysis during cytokinesis. Rng10 and Rga7 colocalize on the plasma membrane at the cell tips during interphase and at the division site during cell division. Rng10 physically interacts with Rga7 in affinity purification and coimmunoprecipitation. Of interest, Rga7 localization is nearly abolished without Rng10. Moreover, Rng10 and Rga7 work together to regulate the accumulation and dynamics of glucan synthases for successful septum formation in cytokinesis. Our results show that cellular localization and function of the Rho GAP Rga7 are regulated by a novel protein, Rng10, during cytokinesis in fission yeast. PMID- 27385339 TI - Ribosomal proteins produced in excess are degraded by the ubiquitin-proteasome system. AB - Ribosome assembly is an essential process that consumes prodigious quantities of cellular resources. Ribosomal proteins cannot be overproduced in Saccharomyces cerevisiae because the excess proteins are rapidly degraded. However, the responsible quality control (QC) mechanisms remain poorly characterized. Here we demonstrate that overexpression of multiple proteins of the small and large yeast ribosomal subunits is suppressed. Rpl26 overexpressed from a plasmid can be detected in the nucleolus and nucleoplasm, but it largely fails to assemble into ribosomes and is rapidly degraded. However, if the endogenous RPL26 loci are deleted, plasmid-encoded Rpl26 assembles into ribosomes and localizes to the cytosol. Chemical and genetic perturbation studies indicate that overexpressed ribosomal proteins are degraded by the ubiquitin-proteasome system and not by autophagy. Inhibition of the proteasome led to accumulation of multiple endogenous ribosomal proteins in insoluble aggregates, consistent with the operation of this QC mechanism in the absence of ribosomal protein overexpression. Our studies reveal that ribosomal proteins that fail to assemble into ribosomes are rapidly distinguished from their assembled counterparts and ubiquitinated and degraded within the nuclear compartment. PMID- 27385340 TI - Pho4 mediates phosphate acquisition in Candida albicans and is vital for stress resistance and metal homeostasis. AB - During interactions with its mammalian host, the pathogenic yeast Candida albicans is exposed to a range of stresses such as superoxide radicals and cationic fluxes. Unexpectedly, a nonbiased screen of transcription factor deletion mutants revealed that the phosphate-responsive transcription factor Pho4 is vital for the resistance of C. albicans to these diverse stresses. RNA-Seq analysis indicated that Pho4 does not induce stress-protective genes directly. Instead, we show that loss of Pho4 affects metal cation toxicity, accumulation, and bioavailability. We demonstrate that pho4Delta cells are sensitive to metal and nonmetal cations and that Pho4-mediated polyphosphate synthesis mediates manganese resistance. Significantly, we show that Pho4 is important for mediating copper bioavailability to support the activity of the copper/zinc superoxide dismutase Sod1 and that loss of Sod1 activity contributes to the superoxide sensitivity of pho4Delta cells. Consistent with the key role of fungal stress responses in countering host phagocytic defenses, we also report that C. albicans pho4Delta cells are acutely sensitive to macrophage-mediated killing and display attenuated virulence in animal infection models. The novel connections between phosphate metabolism, metal homeostasis, and superoxide stress resistance presented in this study highlight the importance of metabolic adaptation in promoting C. albicans survival in the host. PMID- 27385341 TI - Abelson kinase acts as a robust, multifunctional scaffold in regulating embryonic morphogenesis. AB - Abelson family kinases (Abls) are key regulators of cell behavior and the cytoskeleton during development and in leukemia. Abl's SH3, SH2, and tyrosine kinase domains are joined via a linker to an F-actin-binding domain (FABD). Research on Abl's roles in cell culture led to several hypotheses for its mechanism of action: 1) Abl phosphorylates other proteins, modulating their activity, 2) Abl directly regulates the cytoskeleton via its cytoskeletal interaction domains, and/or 3) Abl is a scaffold for a signaling complex. The importance of these roles during normal development remains untested. We tested these mechanistic hypotheses during Drosophila morphogenesis using a series of mutants to examine Abl's many cell biological roles. Strikingly, Abl lacking the FABD fully rescued morphogenesis, cell shape change, actin regulation, and viability, whereas kinase-dead Abl, although reduced in function, retained substantial rescuing ability in some but not all Abl functions. We also tested the function of four conserved motifs in the linker region, revealing a key role for a conserved PXXP motif known to bind Crk and Abi. We propose that Abl acts as a robust multidomain scaffold with different protein motifs and activities contributing differentially to diverse cellular behaviors. PMID- 27385343 TI - Eps15 membrane-binding and -bending activity acts redundantly with Fcho1 during clathrin-mediated endocytosis. AB - Clathrin coat assembly on membranes requires cytosolic adaptors and accessory proteins, which bridge triskeleons with the lipid bilayer and stabilize lattice architecture throughout the process of vesicle formation. In Caenorhabditis elegans, the prototypical AP-2 adaptor complex, which is activated by the accessory factor Fcho1 at the plasma membrane, is dispensable during embryogenesis, enabling us to define alternative mechanisms that facilitate clathrin-mediated endocytosis. Here we uncover a synthetic genetic interaction between C. elegans Fcho1 (FCHO-1) and Eps15 (EHS-1), suggesting that they function in a parallel and potentially redundant manner. Consistent with this idea, we find that the FCHO-1 EFC/F-BAR domain and the EHS-1 EH domains exhibit highly similar membrane-binding and -bending characteristics in vitro. Furthermore, we demonstrate a critical role for EHS-1 when FCHO-1 membrane binding and -bending activity is specifically eliminated in vivo. Taken together, our data highlight Eps15 as an important membrane-remodeling factor, which acts in a partially redundant manner with Fcho proteins during the earliest stages of clathrin-mediated endocytosis. PMID- 27385342 TI - Altered RNA processing and export lead to retention of mRNAs near transcription sites and nuclear pore complexes or within the nucleolus. AB - Many protein factors are required for mRNA biogenesis and nuclear export, which are central to the eukaryotic gene expression program. It is unclear, however, whether all factors have been identified. Here we report on a screen of >1000 essential gene mutants in Saccharomyces cerevisiae for defects in mRNA processing and export, identifying 26 mutants with defects in this process. Single-molecule FISH data showed that the majority of these mutants accumulated mRNA within specific regions of the nucleus, which included 1) mRNAs within the nucleolus when nucleocytoplasmic transport, rRNA biogenesis, or RNA processing and surveillance was disrupted, 2) the buildup of mRNAs near transcription sites in 3'-end processing and chromosome segregation mutants, and 3) transcripts being enriched near nuclear pore complexes when components of the mRNA export machinery were mutated. These data show that alterations to various nuclear processes lead to the retention of mRNAs at discrete locations within the nucleus. PMID- 27385344 TI - Interaction of Gcn4 with target gene chromatin is modulated by proteasome function. AB - The ubiquitin-proteasome system (UPS) influences gene transcription in multiple ways. One way in which the UPS affects transcription centers on transcriptional activators, the function of which can be stimulated by components of the UPS that also trigger their destruction. Activation of transcription by the yeast activator Gcn4, for example, is attenuated by mutations in the ubiquitin ligase that mediates Gcn4 ubiquitylation or by inhibition of the proteasome, leading to the idea that ubiquitin-mediated proteolysis of Gcn4 is required for its activity. Here we probe the steps in Gcn4 activity that are perturbed by disruption of the UPS. We show that the ubiquitylation machinery and the proteasome control different steps in Gcn4 function and that proteasome activity is required for the ability of Gcn4 to bind to its target genes in the context of chromatin. Curiously, the effect of proteasome inhibition on Gcn4 activity is suppressed by mutations in the ubiquitin-selective chaperone Cdc48, revealing that proteolysis per se is not required for Gcn4 activity. Our data highlight the role of Cdc48 in controlling promoter occupancy by Gcn4 and support a model in which ubiquitylation of activators-not their destruction-is important for function. PMID- 27385345 TI - Cofilin-mediated actin dynamics promotes actin bundle formation during Drosophila bristle development. AB - The actin bundle is an array of linear actin filaments cross-linked by actin bundling proteins, but its assembly and dynamics are not as well understood as those of the branched actin network. Here we used the Drosophila bristle as a model system to study actin bundle formation. We found that cofilin, a major actin disassembly factor of the branched actin network, promotes the formation and positioning of actin bundles in the developing bristles. Loss of function of cofilin or AIP1, a cofactor of cofilin, each resulted in increased F-actin levels and severe defects in actin bundle organization, with the defects from cofilin deficiency being more severe. Further analyses revealed that cofilin likely regulates actin bundle formation and positioning by the following means. First, cofilin promotes a large G-actin pool both locally and globally, likely ensuring rapid actin polymerization for bundle initiation and growth. Second, cofilin limits the size of a nonbundled actin-myosin network to regulate the positioning of actin bundles. Third, cofilin prevents incorrect assembly of branched and myosin-associated actin filament into bundles. Together these results demonstrate that the interaction between the dynamic dendritic actin network and the assembling actin bundles is critical for actin bundle formation and needs to be closely regulated. PMID- 27385347 TI - The risk to the cutaneous nerve branches in the anterior (Wagner) and snuff-box approaches to the trapezium: a cadaveric study. AB - We compared the risk with the subcutaneous nerves with the anterior (Wagner) and snuff-box approaches to the trapezium in cadavers. Branches that crossed tattooed incision markings or lay within 1 cm of the markings were identified on six matched pairs of fresh-frozen cadaveric hands. Their distance from the proximal end of the incision was recorded. For anterior incisions, there were 20 vulnerable branches in total, at a mean distance of 22 mm from the proximal end of the incision. A total of 13 lay in the distal half of the incision. For snuff box incisions, there were 18 vulnerable branches in total, at a mean distance of 11 mm from the proximal end of the incision, with 17 of them lying in the proximal half of the incision. Neither incision is without risk to nerve braches, but our study suggests a lesser risk of subcutaneous nerve damage with the snuff box approach and highlights the greater risk in the proximal half of this incision. PMID- 27385346 TI - MSK1 triggers the expression of the INK4AB/ARF locus in oncogene-induced senescence. AB - The tumor suppressor proteins p15(INK4B), p16(INK4A), and p14(ARF), encoded by the INK4AB/ARF locus, are crucial regulators of cellular senescence. The locus is epigenetically silenced by the repressive Polycomb complexes in growing cells but is activated in response to oncogenic stress. Here we show that the mitogen- and stress-activated kinase (MSK1) is up-regulated after RAF1 oncogenic stress and that the phosphorylated (activated) form of MSK1 is significantly increased in the nucleus and recruited to the INK4AB/ARF locus. We show that MSK1 mediates histone H3S28 phosphorylation at the INK4AB/ARF locus and contributes to the rapid transcriptional activation of p15(INK4B) and p16(INK4A) in human cells despite the presence of the repressive H3K27me3 mark. Furthermore, we show that upon MSK1 depletion in oncogenic RAF1-expressing cells, H3S28ph presence at the INK4 locus and p15(INK4B) and p16(INK4A) expression are reduced. Finally, we show that H3S28-MSK-dependent phosphorylation functions in response to RAF1 signaling and that ERK and p38alpha contribute to MSK1 activation in oncogene-induced senescence. PMID- 27385350 TI - A letter to the Editor on 'Validation protocols for blood pressure-measuring devices: status quo and development needs' by Beime et al., Blood Press Monit 2016; 21:1-8. PMID- 27385351 TI - Response to the letter to the Editor regarding 'Validation protocols for blood pressure-measuring devices: status quo and development needs' by Bruce Alpert. PMID- 27385349 TI - Comparison of immunogenicity and persistence between inactivated hepatitis A vaccine Healive(r) and Havrix(r) among children: A 5-year follow-up study. AB - BACKGROUND: Inactivated vaccines for hepatitis A virus (HAV) infection are widely used in China. Mass vaccination programs drive the need for data on long-term persistence of vaccine-induced protection. METHODS: A prospective, randomized, open-label clinical trial was conducted to compare geometric mean concentrations (GMCs) and seroconversion rates (SRs) of anti-HAV antibody elicited by the inactivated vaccines Healive and Havrix for 5 y post immunization, in which 400 healthy children were randomly assigned in a 3:1 ratio to receive 2 doses of Healive or Havrix at 0 and 6 month. Anti-HAV antibody concentration was detected by microparticle enzyme immunoassay (MEIA) during the study. Furthermore, an attempt was made to predict persistence of protective immunogenicity by using a suitable statistical model. RESULTS: The GMCs were significantly higher after vaccination with Healive than after Havrix as comparator vaccine at 1, 6, 7, 18, 30, 42, 54 and 66 month (P < 0.01) with the peak point at 7 month (3427.2 mIU/ml for Healive and 1441.9 mIU/ml for Comparator). Similarly significant differences of SRs were found between the 2 groups at 1 and 6 month (P < 0.01). Afterwards, the SRs of both groups reached 100% at 7 month and did not decline until 66 month(99.1% for Healive and 97.5% for Comparator). A linear mixed model with a change point at 18 month(Model 3) was found to be suitable to predict persistence of protective immunogenicity induced by vaccines. It was estimated that the duration of protection for Healive was at least 20 y with a lower limit of GMC 95% confidence interval (CI) no less than 20 mIU/mL. CONCLUSIONS: Compared with Havrix, the new preservative-free inactivated hepatitis A vaccine (Healive) in 2 doses showed better persistence of antibody concentrations for 5 y after full course immunization among children and the persistence of protective immunogenicity was estimated for at least 20 y. PMID- 27385352 TI - William M. Gelbart: An Appreciation. PMID- 27385354 TI - Colleagues of William M. Gelbart. PMID- 27385353 TI - Biography of William M. Gelbart. PMID- 27385355 TI - Abbreviated Curriculum Vitae of William M. Gelbart. PMID- 27385356 TI - Publications of William M. Gelbart. PMID- 27385357 TI - Quantitative filter forensics for indoor particle sampling. AB - Filter forensics is a promising indoor air investigation technique involving the analysis of dust which has collected on filters in central forced-air heating, ventilation, and air conditioning (HVAC) or portable systems to determine the presence of indoor particle-bound contaminants. In this study, we summarize past filter forensics research to explore what it reveals about the sampling technique and the indoor environment. There are 60 investigations in the literature that have used this sampling technique for a variety of biotic and abiotic contaminants. Many studies identified differences between contaminant concentrations in different buildings using this technique. Based on this literature review, we identified a lack of quantification as a gap in the past literature. Accordingly, we propose an approach to quantitatively link contaminants extracted from HVAC filter dust to time-averaged integrated air concentrations. This quantitative filter forensics approach has great potential to measure indoor air concentrations of a wide variety of particle-bound contaminants. Future studies directly comparing quantitative filter forensics to alternative sampling techniques are required to fully assess this approach, but analysis of past research suggests the enormous possibility of this approach. PMID- 27385358 TI - Outdoor PM2.5, Ambient Air Temperature, and Asthma Symptoms in the Past 14 Days among Adults with Active Asthma. AB - BACKGROUND: Relationships between air quality and health are well-described, but little information is available about the joint associations between particulate air pollution, ambient temperature, and respiratory morbidity. OBJECTIVES: We evaluated associations between concentrations of particulate matter <= 2.5 MUm in diameter (PM2.5) and exacerbation of existing asthma and modification of the associations by ambient air temperature. METHODS: Data from 50,356 adult respondents to the Asthma Call-back Survey from 2006-2010 were linked by interview date and county of residence to estimates of daily averages of PM2.5 and maximum air temperature. Associations between 14-day average PM2.5 and the presence of any asthma symptoms during the 14 days leading up to and including the interview date were evaluated using binomial regression. We explored variation by air temperature using similar models, stratified into quintiles of the 14-day average maximum temperature. RESULTS: Among adults with active asthma, 57.1% reported asthma symptoms within the past 14 days, and 14-day average PM2.5 >= 7.07 MUg/m3 was associated with an estimated 4-5% higher asthma symptom prevalence. In the range of 4.00-7.06 MUg/m3 of PM2.5, each 1-MUg/m3 increase was associated with a 3.4% [95% confidence interval (CI): 1.1, 5.7] increase in symptom prevalence; across categories of temperature from 1.1 to 80.5 degrees F, each 1-MUg/m3 increase was associated with increased symptom prevalence (1.1-44.4 degrees F: 7.9%; 44.5-58.6 degrees F: 6.9%; 58.7-70.1 degrees F: 2.9%; 70.2-80.5 degrees F: 7.3%). CONCLUSIONS: These results suggest that each unit increase in PM2.5 may be associated with an increase in the prevalence of asthma symptoms, even at levels as low as 4.00-7.06 MUg/m3. Citation: Mirabelli MC, Vaidyanathan A, Flanders WD, Qin X, Garbe P. 2016. Outdoor PM2.5, ambient air temperature, and asthma symptoms in the past 14 days among adults with active asthma. Environ Health Perspect 124:1882-1890; http://dx.doi.org/10.1289/EHP92. PMID- 27385359 TI - Potential toxicity of engineered nanoparticles in mammalian germ cells and developing embryos: treatment strategies and anticipated applications of nanoparticles in gene delivery. AB - BACKGROUND: Engineered nanoparticles (ENPs) offer technological advantages for a variety of industrial and consumer products as well as show promise for biomedical applications. Recent progress in the field of nanotechnology has led to increased exposure to nanoparticles by humans. To date, little is known about the adverse effects of these ENPs on reproductive health, although interest in nanotechnology area is growing. A few biocompatible ENPs have a high loading capacity for exogenous substances, including drugs, DNA or proteins, and can selectively deliver molecular cargo into cells; however, they represent a potential tool for gene delivery into gametes and embryos. OBJECTIVE AND RATIONALE: Understanding the reprotoxicological aspects of these ENPs is of the utmost importance to reliably estimate its potential impact on human health. In addition, a search for protective agents to combat ENP-mediated reproductive toxicity is warranted. Therefore, in this review we summarize the toxic effects of a few ENPs (metal and metal oxides, carbon-based nanoparticles, quantum dots and chitosan) in mammalian germ cells and developing embryos, and propose some treatment strategies that could mitigate nanoparticle-mediated toxicity. In addition, we outline the anticipated applications of ENPs in transgenic animal production in order to generate models for investigations into the mechanisms for human disease. SEARCH METHODS: A literature search was performed using the National Center for Biotechnology Information PubMed database up until March 2016 and relevant keywords were used to obtain information regarding mammalian germ cell-specific toxicity and embryotoxicity of ENPs, possible treatment strategies, as well as the anticipated applications of nanoparticles in gene delivery in germ cells and embryos. Only English language publications were included. OUTCOMES: Here, we demonstrate the toxicological effects of ENPs in mammalian germ cells and developing embryos by considering both in vitro and in vivo experimental models based on the existing literature. The biodistribution and cellular uptake of ENPs and the observed toxicities are mostly dependent on ENP size and surface coating agents (surface functional groups/surface charge). ENPs have been shown to induce toxicity via oxidative stress, inflammation and DNA damage in both human and mouse germ cells. Use of antioxidant, anti-inflammatory drugs and selective metal chelators would be beneficial against nanoparticle-induced toxicity. WIDER IMPLICATIONS: Our review provides the reproductive scientists a mechanistic insight into the reprotoxicological aspects of ENPs to reliably estimate its potential impact on human health and help to select/design protective agents to combat ENP-mediated toxicity. Furthermore, research regarding the detailed mechanism(s) of ENP toxicity in mammalian germ cells and developing embryos as well as the search for protective agents to combat ENP mediated reproductive toxicity is warranted. Furthermore, we anticipate that investigations into the possibility of applying nanovectors to gene delivery in germ cells and early embryos will open new horizons in reproductive biology. PMID- 27385361 TI - In Vivo Monitoring of H2O2 with Polydopamine and Prussian Blue-coated Microelectrode. AB - In vivo monitoring of hydrogen peroxide (H2O2) in the brain is of importance for understanding the function of both reactive oxygen species (ROS) and signal transmission. Producing a robust microelectrode for in vivo measurement of H2O2 is challenging due to the complex brain environment and the instability of electrocatalysts employed for the reduction of H2O2. Here, we develop a new kind of microelectrode for in vivo monitoring of H2O2, which is prepared by, first, electrodeposition of Prussian blue (PB) onto carbon nanotube (CNT) assembled carbon fiber microelectrodes (CFEs) and then overcoating of the CFEs with a thin membrane of polydopamine (PDA) through self-polymerization. Scanning electron microscopic and X-ray proton spectroscopic results confirm the formation of PDA/PB/CNT/CFEs. The PDA membrane enables PB-based electrodes to show high stability in both in vitro and in vivo studies and to stably catalyze the electrochemical reduction of H2O2. The microelectrode is selective for in vivo measurements of H2O2, interference-free from O2 and other electroactive species coexisting in the brain. These properties, along with good linearity, high biocompatibility, and stability toward H2O2, substantially enable the microelectrode to track H2O2 changes in vivo during electrical stimulation and microinfusion of H2O2 and drug, which demonstrates that the microelectrode could be well suited for in vivo monitoring of dynamic changes of H2O2 in rat brain. PMID- 27385362 TI - Group B streptococcal immunisation of pregnant women for the prevention of early and late onset Group B streptococcal infection of the neonate as well as adult disease. AB - INTRODUCTION: Early onset neonatal Group B streptococcal disease is preventable. Intrapartum antibiotic prophylaxis has resulted in a significant reduction in neonatal mortality and morbidity. National guidelines for the selection of women eligible for intrapartum antibiotic prophylaxis, whether screening-based or risk based, differ according to the local burden of disease. Despite the introduction of intrapartum antibiotic prophylaxis, there remains a significant burden of disease, which can be resolved by better adherence to guidelines, rapid identification of maternal colonization or in the future, vaccination. Areas covered: The introduction of a vaccine to women in the third trimester is likely to further reduce the burden of disease and provide benefits beyond the prevention of early neonatal disease, including meningitis and disability following late onset disease. Development of specific polyvalent vaccines continues, but testing has challenges and may require surrogate markers or molecular-based techniques to manipulate antigenicity and immunogenicity. Expert commentary: Group B streptococcal vaccination using conjugated polyvalent vaccines against the major disease causing serotypes of Group B streptococcus, either alone, or in combination with a policy of intrapartum antibiotic prophylaxis, may decrease the burden of Group B streptococcus beyond that achieved by current use of intrapartum antibiotic prophylaxis alone. PMID- 27385363 TI - Socioeconomic Disparities in the Presentation and Treatment of Graves' Disease and Thyroid Eye Disease. AB - Thyroid eye disease (TED) is an inflammatory, autoimmune orbitopathy with multifactorial etiology. Clinical presentation of TED spans a range from mild surface irritation to vision threatening compressive optic neuropathy. Potential vision loss underscores the importance of understanding genetic and environmental factors influencing the severity of TED presentation. This review will describe the classic risk factors for TED, outline treatments for Graves' disease (GD) and TED, and describe newer evidence of socioeconomic disparities in TED presentation. PMID- 27385364 TI - Trauma informed care: a radical shift or basic good practice? AB - OBJECTIVE: There is significant multidisciplinary work contributing to the implementation of trauma informed care (TIC) into mental health policy and practice in Australia. Within psychiatry, there may be potential confusion about how to navigate the integration of TIC into a speciality built upon treating psychological distress; creating dismissive reactions of a patronising approach and paradoxical radicalism. This paper aims to discuss the need for psychiatry to view TIC as a significant and urgent paradigm shift required to integrate existing knowledge about the prevalence and effects of trauma into a progressive articulation of the relational and interpersonal underpinnings of modern psychiatric practice; and to lead and support its widespread implementation. CONCLUSION: Active consideration of the intent of TIC may aid in reducing misunderstanding and misaligned resistance while allowing services and individuals an important opportunity to reflect on how to deliver mental health treatment that is universally sensitive to the dynamics of trauma in the care environment. PMID- 27385360 TI - G-Protein-coupled receptors as potential drug candidates in preeclampsia: targeting the relaxin/insulin-like family peptide receptor 1 for treatment and prevention. AB - BACKGROUND: Important roles for G-protein-coupled receptors (GPCRs) have been identified in the maternal physiological adaptations to pregnancy and in the pathogenesis of preeclampsia. On this basis, GPCRs are potential therapeutic targets for preeclampsia. OBJECTIVES AND RATIONALE: In this review, vasopressin and apelin are initially considered in this context before the focus on the hormone relaxin and its cognate receptor, the relaxin/insulin-like family peptide receptor 1 (RXFP1). Based on both compelling scientific rationale and a promising safety profile, the relaxin ligand-receptor system is comprehensively evaluated as a potential therapeutic endpoint in preeclampsia. SEARCH METHODS: The published literature relating to the topic was searched through January 2016 using PubMed. OUTCOMES: Relaxin is a peptide hormone secreted by the corpus luteum; it circulates in the luteal phase and during pregnancy. Activation of RXFP1 is vasodilatory; thus, relaxin supplementation is expected to at least partly restore the fundamental vasodilatory changes of normal pregnancy, thereby alleviating maternal organ hypoperfusion, which is a major pathogenic manifestation of severe preeclampsia. Specifically, by exploiting its pleiotropic hemodynamic attributes in preeclampsia, relaxin administration is predicted to (i) reverse robust arterial myogenic constriction; (ii) blunt systemic and renal vasoconstriction in response to activation of the angiotensin II receptor, type 1; (iii) mollify the action of endogenous vasoconstrictors on uterine spiral arteries with failed remodeling and retained smooth muscle; (iv) increase arterial compliance; (v) enhance insulin-mediated glucose disposal by promoting skeletal muscle vasodilation and (vi) mobilize and activate bone marrow-derived angiogenic progenitor cells, thereby repairing injured endothelium and improving maternal vascularity in organs such as breast, uterus, pancreas, skin and fat. By exploiting its pleiotropic molecular attributes in preeclampsia, relaxin supplementation is expected to (i) enhance endothelial nitric oxide synthesis and bioactivity, as well as directly reduce vascular smooth muscle cytosolic calcium, thus promoting vasodilation; (ii) improve the local angiogenic balance by augmenting arterial vascular endothelial and placental growth factor (VEGF and PLGF) activities; (iii) ameliorate vascular inflammation; (iv) enhance placental peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PCG1alpha) expression, and hence, peroxisome proliferator-activated receptor gamma (PPAR gamma) activity and (v) confer cytotrophoblast and endothelial cytoprotection. Insofar as impaired endometrial maturation (decidualization) predisposes to the development of preeclampsia, relaxin administration in the late secretory phase and during early pregnancy would be anticipated to improve decidualization, and hence trophoblast invasion and spiral artery remodeling, thereby reducing the risk of preeclampsia. Relaxin has a favorable safety profile both in the non pregnant condition and during pregnancy. WIDER IMPLICATIONS: There is a strong scientific rationale for RXFP1 activation in severe preeclampsia by administration of relaxin, relaxin analogs or small molecule mimetics, in order to mollify the disease pathogenesis for safe prolongation of pregnancy, thus allowing time for more complete fetal maturation, which is a primary therapeutic endpoint in treating the disease. In light of recent data implicating deficient or defective decidualization as a potential etiological factor in preeclampsia and the capacity of relaxin to promote endometrial maturation, the prophylactic application of relaxin to reduce the risk of preeclampsia is a plausible therapeutic approach to consider. Finally, given its pleiotropic and beneficial attributes particularly in the cardiovascular system, relaxin, although traditionally considered as a 'pregnancy' hormone, is likely to prove salutary for several disease indications in the non-pregnant population. PMID- 27385365 TI - How Large Is the Role of Emotion in Judgments of Moral Dilemmas? AB - Moral dilemmas often pose dramatic and gut-wrenching emotional choices. It is now widely accepted that emotions are not simply experienced alongside people's judgments about moral dilemmas, but that our affective processes play a central role in determining those judgments. However, much of the evidence purporting to demonstrate the connection between people's emotional responses and their judgments about moral dilemmas has recently been called into question. In the present studies, we reexamined the role of emotion in people's judgments about moral dilemmas using a validated self-report measure of emotion. We measured participants' specific emotional responses to moral dilemmas and, although we found that moral dilemmas evoked strong emotional responses, we found that these responses were only weakly correlated with participants' moral judgments. We argue that the purportedly strong connection between emotion and judgments of moral dilemmas may have been overestimated. PMID- 27385367 TI - The Effects of Salicylic Acid on Juvenile Zebrafish Danio rerio Under Flow Through Conditions. AB - The aquatic environment is becoming increasingly contaminated with pharmaceuticals. Salicylic acid (SA), which can be used individually or appear as a degradation product of the widely used acetylsalicylic acid was chosen for testing. Juvenile zebrafish Danio rerio were subjected to OECD test No. 215 (fish, juvenile growth test) with salicylic acid concentrations of 0.004; 0.04; 0.4; 4 and 40 mg/L. Specific growth rate (SGR), histological changes, and parameters of oxidative stress were evaluated. SA had no effects on histological changes, SGR, glutathione reductase, and lipid peroxidation. Increased catalytic activity of GPx was found at 0.04 mg/L compared to control, increased catalytic activity of catalase was found at 0.04 and 4 mg/L compared to control, and increased catalytic activity of glutathione-S-transferase was found at 0.004 and 0.04 mg/L compared to control (P < 0.05). Juvenile zebrafish turned out to be relatively insensitive to both environmentally relevant (0.004 mg/L) and higher concentrations of salicylic acid. PMID- 27385366 TI - A miR-335/COX-2/PTEN axis regulates the secretory phenotype of senescent cancer associated fibroblasts. AB - Senescent cancer-associated fibroblasts (CAF) develop a senescence-associated secretory phenotype (SASP) that is believed to contribute to cancer progression. The mechanisms underlying SASP development are, however, poorly understood. Here we examined the functional role of microRNA in the development of the SASP in normal fibroblasts and CAF. We identified a microRNA, miR-335, up-regulated in the senescent normal fibroblasts and CAF and able to modulate the secretion of SASP factors and induce cancer cell motility in co-cultures, at least in part by suppressing the expression of phosphatase and tensin homologue (PTEN). Additionally, elevated levels of cyclo-oxygenase 2 (PTGS2; COX-2) and prostaglandin E2 (PGE2) secretion were observed in senescent fibroblasts, and inhibition of COX-2 by celecoxib reduced the expression of miR-335, restored PTEN expression and decreased the pro-tumourigenic effects of the SASP. Collectively these data demonstrate the existence of a novel miRNA/PTEN-regulated pathway modulating the inflammasome in senescent fibroblasts. PMID- 27385368 TI - Evaluation of Molecular Markers and Analytical Methods Documenting the Occurrence of Mustard Gas and Arsenical Warfare Agents in Soil. AB - The chemicals warfare agents (CWAs) are an extremely toxic class of molecules widely produced in many industrialized countries for decades, these compounds frequently contained arsenic. The plants where the CWAs have been produced or the plants where they have been demilitarized after the Second World War with unacceptable techniques can represent a serious environmental problem. CWAs standards are difficult to find on market so in present work an environmental assessment method based on markers has been proposed. Triphenylarsine, phenylarsine oxide and thiodiglycol have been selected as markers. Three reliable analytical methods based on gaschromatography and mass detection have been proposed and tested for quantitative analysis of markers. Methods performance have been evaluated testing uncertainty, linearity, recovery and detection limits and also comparing detection limits with exposure limits of reference CWAs. Proposed assessment methods have been applied to a case study of a former industrial plant sited in an area characterized by a high background of mineral arsenic. PMID- 27385369 TI - Determination of PCB Elimination Coefficients in Round Goby and Tubenose Goby. AB - Whole-body elimination coefficients of polychlorinated biphenyls (PCBs) were determined in two Great Lakes invasive fish species, round goby (Neogobius melanostomus) and tubenose goby (Proterorhinus semilunaris). Elimination rates were determined for a set of model PCB congeners (n = 12 congeners) dosed to fish by intraperitoneal injection and allowed to depurate at a temperature of 21.4 degrees C for 90 days. Eight PCBs (PCB 6, 21, 57, 62, 68, 89, 112 and 125) exhibited significant elimination by round goby and had corresponding half lives ranging from 13 to 39.8 days. For tubenose goby, four congeners (PCBs 21, 57, 62 and 68) exhibited significant elimination with half lives in the range from 18.8 to 48.8 days. Whole-body elimination rate coefficients were significantly higher for round gobies compared to tubenose goby. In both cases, PCB elimination rate coefficients were negatively related to chemical log KOW. PMID- 27385370 TI - Bioaugmentation-Assisted Phytostabilisation of Abandoned Mine Sites in South West Sardinia. AB - Bioaugmentation-assisted phytoremediation implies the administration of selected plant growth promoting bacteria, which significantly improve plant growth and sequestration of heavy metals. In this work, 184 bacterial strains associated with roots of Pistacia lentiscus were isolated from plants spontaneously growing in the abandoned Sardinian mining areas (SW Sardinia, Italy) and phylogenetically characterised. Twenty-one bacterial isolates were assayed for properties relevant for plant growth promotion and metal tolerance. Five different strains, belonging to the genera Novosphingobium, Variovorax, Streptomyces, Amycolatopsis, Pseudomonas, were selected based on their properties for the greenhouse phytoremediation tests. Among the tested inocula, the strain Variovorax sp. RA128A, able to produce ACC deaminase and siderophore, was able to significantly enhance germination and increase length and weight of shoots and roots. Irrespective of the applied treatment, mastic shrub was able to accumulate Cd, Pb and Zn especially in roots. PMID- 27385371 TI - Joint Toxicity of Two Phthalates with Waterborne Copper to Daphnia magna and Photobacterium phosphoreum. AB - Di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) are two widely used phthalates, while Cu(II) is a common valence state of copper. They have been ubiquitously detected in the aquatic environment, but information on their joint toxicity to aquatic organisms is scarce. In this study, we evaluated the combined effects of copper and these two phthalates to Daphnia magna and Photobacterium phosphoreum by quantifying the acute toxicity expressed by the EC50 (the concentration causing 50 % of maximal effect) value. The toxicity order was DEHP + Cu(II) > DBP + Cu(II) > Cu(II) > DEHP > DBP for both test species. Antagonism effects were found in the joint toxicity of Cu(II) combined with DBP or DEHP using the toxic unit method. These findings have important implications in environmental risk assessment for phthalates in the aquatic environment in the presence of heavy metals. PMID- 27385372 TI - Quantitative Biomonitoring in the Detroit River Using Elliptio complanata: Verification of Steady State Correction Factors and Temporal Trends of PCBs in Water Between 1998 and 2015. AB - Quantitative biomonitoring methods were applied to determine PCB concentrations in water from the Detroit River over a 17 year period. During 2014, mussels were deployed for and extended duration (21-364 days) and time dependent PCB concentrations were fit to a bioaccumulation model to estimate elimination coefficients (ktot) and provide site specific calibration of mussel toxicokinetics. The site specific calibration and different ktot versus KOW relationships from the literature were used to correct for steady state. ?PCB concentrations in water were not significantly dependent on the ktot values used indicating that individual variation exceeds error contributed by steady state correction factors. The model was then applied to estimate ?PCB concentrations in water using the long term (1998-2015) data. ?PCBs concentrations in water exhibited a significant decreasing trend with a half life of 9.12 years resulting in a drop in yearly geometric mean residues from 198.1 to 43.6 pg/L. PMID- 27385373 TI - The safety of autologous and metabolically fit bone marrow mesenchymal stromal cells in medically refractory Crohn's disease - a phase 1 trial with three doses. AB - BACKGROUND: Mesenchymal stromal cells ability to reset immune functionalities may be useful in Crohn's disease. AIM: To perform a first-in-human phase 1 safety clinical trial of metabolically fit autologous bone marrow-derived mesenchymal stromal cells in 12 subjects with Crohn's disease utilising three doses. METHODS: Autologous mesenchymal stromal cells were derived from marrow aspirate and propagated for 2-3 weeks with fibrinogen depleted human platelet lysate and subsequently administered to subjects without interval cryobanking. Twelve subjects received a single mesenchymal stromal cell intravenous infusion of 2, 5 or 10 million cells/kg BW(n = 4/group). Infused mesenchymal stromal cells were analysed for cell surface marker expression, IDO(indoleamine 2,3-dioxygenase) upregulation by IFNgamma stimulation, and inhibition of third party peripheral blood mononuclear cell proliferation in vitro. The primary end point measured was safety and tolerability; clinical response was assessed as a secondary endpoint. RESULTS: All patients tolerated the mesenchymal stromal cell infusion well and no dose limiting toxicity was seen. Seven patients had serious adverse events of which five were hospitalisations for Crohn's disease flare. Two of these serious adverse events were possibly related to the mesenchymal stromal cells infusion. Five subjects showed clinical response 2 weeks after the infusion. Mesenchymal stromal cell phenotype, cytokine responsiveness, and peripheral blood mononuclear cell proliferation blockade were not different among the patients. CONCLUSION: Single infusion of fresh autologous bone marrow mesenchymal stromal cells propagated ex vivo using human platelet lysate-supplemented media was safe and feasible at intravenous doses of up to 10 million cells/kg BW in patients with Crohn's disease. PMID- 27385374 TI - Efficacy, safety and cost per responder of biologics in the treatment of non radiographic axial spondyloarthritis. AB - Anti-tumour necrosis factor (TNF) agents are recommended as second-line therapy for patients with axial spondyloarthropathies. This analysis reviewed data on studies investigating the efficacy and tolerability of anti-TNF agents in patients with non-radiographic axial spondyloarthritis (nr-axSpA) who had failed first-line non-steroidal anti-inflammatory (NSAID) treatment. Efficacy data from RCTs were used to calculate the number needed to treat (NNT) for individual anti TNFs and then the cost per responder was determined to provide an indication of the value of each therapy. A systematic literature review and analysis of search results over the period January 2008 to September 2014 identified four randomised placebo-controlled trials that were included in the analysis. Adalimumab, etanercept and certolizumab pegol were all effective and well tolerated in patients with nr-axSpA. A patient was more likely to reach ASAS20 or ASAS40 when treated with etanercept or adalimumab, the NNT was lowest for adalimumab, and the risk of adverse events was higher with certolizumab pegol 200 mg every 2 weeks. The cost per responder (NNT) was lowest for adalimumab, followed closely by certolizumab 400 mg every 4 weeks, intermediate for certolizumab 200 mg every 2 weeks and highest for etanercept. Although all anti-TNF agents were associated with clinical improvement in patients with nr-axSpA, adalimumab presented a better cost per responder than etanercept and certolizumab pegol. PMID- 27385376 TI - Identifying non-pharmacological risk factors for falling in older adults with type 2 diabetes mellitus: a systematic review. AB - PURPOSE: To identify the non-pharmacological risk factors for falling in older adults with type 2 diabetes mellitus (DM2). METHODS: A systematic review of randomized controlled trials, prospective cohort studies, cross-sectional studies and before/after studies was conducted. Eligible studies identified non pharmacological risk factors for falling in older adults with DM2. Medline, Embase, Pubmed and CINAHL were searched for relevant studies published through December 2015. Reference lists were also searched for relevant studies. Search terms were DM2, risk factors, falls and falling, older adults, aging, non-insulin dependent diabetes mellitus, accidental falls and trip. Publication language was restricted to English. RESULTS: Thirteen studies met the inclusion criteria: four cross-sectional, six prospective cohorts, two randomized controlled trials and one before/after study. These studies included a total of 13,104 participants, >=50 years. The most common risk factors for falling were impaired balance, reduced walking velocity, peripheral neuropathy and comorbid conditions. However, lower extremity pain, being overweight and comorbid conditions had the greatest impact on fall risk. CONCLUSION: Interventions to reduce falling in older adults with type 2 diabetes mellitus should focus on reducing lower extremity pain, reducing body weight and managing comorbid conditions. Implications for Rehabilitation Diabetes mellitus: * Older adults with type 2 diabetes mellitus (DM2) have a higher risk for falling than older adults without. * Older adults with DM2 are more likely to suffer serious injuries when they fall. * Comprehensive risk factor identification is necessary for rehabilitation professionals to accurately determine whether their clients are at risk for falling. * Rehabilitation professionals also need to tailor interventions based on the client's risk factors in order to effectively reduce falls and fall related injuries. PMID- 27385375 TI - Impact of genetic deletion of platform apolipoproteins on the size distribution of the murine lipoproteome. AB - Given their association with cardiovascular disease protection, there has been intense interest in understanding the biology of high density lipoproteins (HDL). HDL is actually a family of diverse particle types, each made up of discrete - but as yet undetermined - combinations of proteins drawn from up to 95 lipophilic plasma proteins. The abundant apolipoproteins (apo) of the A class (apoA-I, apoA II and apoA-IV) have been proposed to act as organizing platforms for auxiliary proteins, but this concept has not been systematically evaluated. We assessed the impact of genetic knock down of each platform protein on the particle size distribution of auxiliary HDL proteins. Loss of apoA-I or apoA-II massively reduced HDL lipids and changed the plasma size pattern and/or abundance of several plasma proteins. Surprisingly though, many HDL proteins were not affected, suggesting they assemble on lipid particles in the absence of apoA-I or apoA-II. In contrast, apoA-IV ablation had minor effects on plasma lipids and proteins, suggesting that it forms particles that largely exclude other apolipoproteins. Overall, the data indicate that distinct HDL subpopulations exist that do not contain, nor depend on, apoA-I, apoA-II or apoA-IV and these contribute substantially to the proteomic diversity of HDL. BIOLOGICAL SIGNIFICANCE: Plasma levels of high density lipoproteins (HDL) are inversely correlated with cardiovascular disease. These particles are becoming known as highly heterogeneous entities that have diverse compositions and functions that may impact disease. Unfortunately, we know little about the forces that maintain the composition of each particle in plasma. It has been suggested that certain 'scaffold' proteins, such as apolipoprotein (apo) A-I, apoA-II and apoA-IV, may act as organizing centers for the docking of myriad accessory proteins. To test this hypothesis, we took advantage of the genetic tractability of the mouse model and ablated these three proteins individually. We then tracked the abundance and size profile of the remaining HDL proteins by gel filtration chromatography combined with mass spectrometry. The results clearly show that certain cohorts of proteins depend on each scaffold molecule to assemble normal sized HDL particles under wild-type conditions. This work forms the basis for more detailed studies that will define the specific compositions of HDL subspecies with the possibility of connecting them to specific functions or roles in disease. PMID- 27385377 TI - Combined Foley's catheter with vaginal misoprostol for pre-induction cervical ripening: A randomised controlled trial. AB - BACKGROUND: Pre-induction cervical ripening greatly influences the outcome of induction of labour (IOL). AIMS: To compare the efficacy of combined Foley's catheter and vaginal misoprostol with Foley's catheter or low-dose vaginal misoprostol alone for cervical ripening. MATERIALS AND METHODS: Women with a singleton pregnancy admitted at term for cervical ripening and IOL based on clinical indication were randomised into three groups. Oxytocin augmentation was done in the groups as indicated. Significant tests were done using chi square, Fisher's exact and analysis of variance tests. RESULTS: A total of 210 women were randomised into the study. Women in the combined group (Foley's catheter and vaginal misoprostol) had significantly higher postcervical ripening Bishop's score than the women in the other two groups; P = 0.001. Cervical ripening time, induction-delivery time and cervical ripening-delivery interval were significantly shorter in the combined group compared to the other two groups; P = 0.001. Also, women in the combined group required significantly lesser oxytocin augmentation than the other two groups; P = 0.001. There was no difference in Apgar scores at 1 or 5 minutes or in special baby care unit admission among the groups. There were no reported cases of uterine contractile abnormalities or rupture in this study. CONCLUSION: Combined Foley's catheter and vaginal misoprostol provide a shorter duration to the achievement of cervical ripening. PMID- 27385378 TI - Respiratory motion correction in 4D-PET by simultaneous motion estimation and image reconstruction (SMEIR). AB - In conventional 4D positron emission tomography (4D-PET), images from different frames are reconstructed individually and aligned by registration methods. Two issues that arise with this approach are as follows: (1) the reconstruction algorithms do not make full use of projection statistics; and (2) the registration between noisy images can result in poor alignment. In this study, we investigated the use of simultaneous motion estimation and image reconstruction (SMEIR) methods for motion estimation/correction in 4D-PET. A modified ordered subset expectation maximization algorithm coupled with total variation minimization (OSEM-TV) was used to obtain a primary motion-compensated PET (pmc PET) from all projection data, using Demons derived deformation vector fields (DVFs) as initial motion vectors. A motion model update was performed to obtain an optimal set of DVFs in the pmc-PET and other phases, by matching the forward projection of the deformed pmc-PET with measured projections from other phases. The OSEM-TV image reconstruction was repeated using updated DVFs, and new DVFs were estimated based on updated images. A 4D-XCAT phantom with typical FDG biodistribution was generated to evaluate the performance of the SMEIR algorithm in lung and liver tumors with different contrasts and different diameters (10-40 mm). The image quality of the 4D-PET was greatly improved by the SMEIR algorithm. When all projections were used to reconstruct 3D-PET without motion compensation, motion blurring artifacts were present, leading up to 150% tumor size overestimation and significant quantitative errors, including 50% underestimation of tumor contrast and 59% underestimation of tumor uptake. Errors were reduced to less than 10% in most images by using the SMEIR algorithm, showing its potential in motion estimation/correction in 4D-PET. PMID- 27385379 TI - Areca Nut Chewing and an Impaired Estimated Glomerular Filtration Rate as Significant Risk Factors for Non-Muscle-Invasive Bladder Cancer Recurrence. AB - The present study sought to investigate the predictive value of preoperative clinicopathological variables, with a special focus on areca nut chewing, on disease recurrence and progression in patients with non-muscle-invasive bladder cancer (NMIBC). Data from 242 patients diagnosed with NMIBC between 2008 and 2013 were analyzed retrospectively. Fifteen clinicopathological variables were analyzed to evaluate their prognostic value. During a mean observation period of 21 months, disease recurrence occurred in 140 patients (57.9%). On multivariate analysis, heavy-areca nut chewing (HR = 2.18, 95% CI: 1.37-3.47), current smoking (HR = 3.09, 95% CI: 1.99-4.80), moderately impaired estimated glomerular filtration rate (eGFR) (HR = 1.76, 95% CI: 1.09-2.83), severely impaired eGFR (HR = 3.32, 95% CI: 1.70-6.48) and tumor grade (HR = 1.94, 95% CI: 1.36-2.77) were independent factors for recurrence, based on which a risk factor model was developed to stratify patients into high, medium and low risk groups. In conclusion, our study suggests that in addition to quitting smoking, quitting areca nut chewing may also reduce the risk of first recurrence in NMBIC patients, monitoring and preserving their renal function may be beneficial as well. Further prospective studies are needed to verify the prognostic significance of these factors and the risk stratification model in this population. PMID- 27385380 TI - Fixed dose of long-acting erythropoietic stimulating agents at higher frequency improves appetite, reduces inflammation and corrects anaemia in patients on haemodialysis. AB - Anaemia is an important issue in patients undergoing haemodialysis. We aimed to identify a better dosing schedule of a fixed monthly dose of continuous erythropoietin receptor activator (CERA) in patients with chronic kidney disease (CKD) on haemodialysis. The CERA dosing schedule included 100 MUg once monthly for 2 months, 50 MUg twice monthly for 2 months and then 100 MUg once monthly for two months. The effectiveness was determined by comparing haematocrit, nutritional status (serum protein and albumin) and inflammatory markers (tumour necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6 and Hepcidin) at the beginning of the study with those at the end of the study. Forty-seven out of 67 patients completed the trial. At the end, haematocrit was significantly higher (34.51 vs 33.22%, P=.004), levels of inflammatory markers were significantly lower (TNF-alpha (30.71 vs 35.67 ng/mL, P=.007), IL-6 (5.12 vs 7.95 ng/mL, P=.033), hepcidin (60.39 vs 74.39 ng/mL, P=.002)), blood glucose levels were significantly lower (112.40 vs 139.02 mg/dL, P=.003) and albumin was significantly higher (4.11 vs 3.98, P=.001). Patients with a better than average response had a lower initial number of red blood cells (3.3 vs 3.6 * 10(6) /mm(3) , P=.025) and a lower IL-1 (3.8 vs 12.9 ng/mL, P=.01). They also had significantly lower blood glucose levels at the end. (91.3 vs 124.0 mg/dL, P=.03). We demonstrate that a fixed monthly dose of CERA at a twice monthly dosing schedule improves nutrition, reduces the inflammation and corrects anaemia in patients on haemodialysis. This finding may provide a new strategy for treating CKD-related anaemia. PMID- 27385382 TI - Distribution of chloramphenicol to tissues, plasma and urine in pigs after oral intake of low doses. AB - Toxic effects of chloramphenicol in humans caused the ban for its use in food producing animals in the EU. A minimum required performance level (MRPL) was specified for chloramphenicol at 0.3 MUg kg(-1) for various matrices, including urine. In 2012, residues of chloramphenicol were found in pig urine and muscle without signs of illegal use. Regarding its natural occurrence in straw, it was hypothesised that this might be the source, straw being compulsory for use as bedding material for pigs in Sweden. Therefore, we investigated if low daily doses of chloramphenicol (4, 40 and 400 MUg/pig) given orally during 14 days could result in residues in pig tissues and urine. A dose-related increase of residues was found in muscle, plasma, kidney and urine (showing the highest levels), but no chloramphenicol was found in the liver. At the lowest dose, residues were below the MRPL in all tissues except in the urine. However, in the middle dose, residues were above the MRPL in all tissues except muscle, and at the highest dose in all matrices. This study proves that exposure of pigs to chloramphenicol in doses occurring naturally in straw could result in residues above the MRPL in plasma, kidney and especially urine. PMID- 27385383 TI - Parvalbumin Interneurons of Central Amygdala Regulate the Negative Affective States and the Expression of Corticotrophin-Releasing Hormone During Morphine Withdrawal. AB - BACKGROUND: The central nucleus of the amygdala (CeA) is a crucial component of the neuronal circuitry mediating aversive emotion. Its role in the negative affective states during drug withdrawal includes changes in opioidergic, GABAergic, and corticotropin-releasing factor neurotransmission. However, the modulation of the neurobiological interconnectivity in the CeA and its effects in the negative reinforcement of drug dependents are poorly understood. METHOD: We performed electrophysiological recordings to assess the membrane excitability of parvalbumin (PV)+ interneurons in the CeA during chronic morphine withdrawal. We tested the morphine withdrawal-induced negative affective states, such as the aversive (assessed by conditioned place aversion), anxiety (assessed by elevated plus maze), and anhedonic-like (assessed by saccharin preference test) behaviors, as well as the mRNA level of corticotropin-releasing hormone (CRH) via optogenetic inhibition or activation of PV+ interneurons in the CeA. RESULT: Chronic morphine withdrawal increased the firing rate of CeA PV+ interneurons. Optogenetic inhibition of the activity of CeA PV+ interneurons attenuated the morphine withdrawal-induced negative affective states, such as the aversive, anxiety, and anhedonic-like behaviors, while direct activation of CeA PV+ interneurons could trigger those negative affective-like behaviors. Optogenetic inhibition of the CeA PV+ interneurons during the morphine withdrawal significantly attenuated the elevated CRH mRNA level in the CeA. CONCLUSION: The activity of PV+ interneurons in the CeA was up-regulated during chronic morphine withdrawal. The activation of PV+ interneurons during morphine withdrawal was crucial for the induction of the negative emotion and the up-regulation of CRH mRNA levels in the CeA. PMID- 27385384 TI - Detailed description of a prepregnancy care program and its impact on maternal glucose control, weight gain, and dropouts. AB - BACKGROUND: The aim of this study was to analyze the clinical and metabolic changes observed during a prepregnancy care (PPC) program. METHODS: We performed a retrospective, observational, cohort study of 104 women with type 1 diabetes initiating a PPC program from 2011 to 2014. The outcomes measured were changes in HbA1c levels, weight and hypoglycemic events during PPC. Risk factors associated with severe hypoglycemia events, achieving the HbA1c target and dropouts were evaluated. RESULTS: HbA1c decreased from 7.2 +/- 0.8% (55.3 +/- 8.8 mmol/mol) to 6.7 +/- 0.9% (49.8 +/- 10.3 mmol/mol) (P < .001) within a median of 14.2 months (interquartile interval 5.4-23.2); 71.2% obtained HbA1c < 7% (53 mmol/mol). HbA1c at the end of PPC was associated with baseline HbA1c (beta = .318, P = .001) and the number of previous pregnancies (beta = .224, P = .038), PPC was accompanied by 1.4 +/- 4.0 kg weight gain (P = .003) without changes in severe hypoglycemic events. The risk factors for severe hypoglycemia were severe hypoglycemic events during the 2 years before (odds ratio [OR] 11.99, confidence interval 95% 1.89-75.95) and PPC duration (OR 1.09, 1.03-1.16). A total of 33 patients (31.7%) dropped out from PPC during follow-up, with dropout being associated with age (OR 1.17, 1.04-1.36) and PPC duration (OR 1.06, 1.02-1.11). CONCLUSIONS: Our PPC program was associated with an improvement in glycemic control without a significant increase in severe hypoglycemic events, although with some weight gain. A considerable number of patients dropped out during follow-up, this being related to older age and a longer duration of the program. This information could be of help to design new and more effective PPC approaches. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27385385 TI - [Tonnis and Kalchschmidt triple pelvic osteotomy]. AB - BACKGROUND: The Tonnis and Kalchschmidt triple pelvic osteotomy (TPO) has been performed at the Klinikum Dortmund for more than 30 years. In more than 5000 cases the TPO has proven its potential to deal with even severe dysplastic hips. TPO can be easily combined with other hip procedures as intertrochanteric osteotomies and even impingement treatment can easily be done. As an elaborate technique TPO respects the growth plates and can therefore also be used for treating Legg-Calve-Perthes disease. PROCEDURE: In most cases only conventional X rays are needed for proving the indication. Further imaging like MRI or CT-scans are only needed in certain cases. In addition EOS(r) is becoming an increasingly useful tool in planning and performing the surgery. For adequate movement of the acetabulum, three clearly defined osteotomies are needed. Current osteosynthesis methods provide an enhanced stability due to a novel technique of screw fixation. This is in line with the general trends towards short hospitalization and early mobilization. THERAPY: A successful treatment requires not only experience in performing the surgical technique, but furthermore an experienced team, including care, physical examination and also pain management. The surgeon should be aware that he is performing highly elective surgery and complications or a poor outcome can significantly reduce the quality of life of the mainly young patients. PMID- 27385386 TI - [Hip arthroplasty after corrective osteotomies : Pelvis and proximal femur]. AB - BACKGROUND: Pelvic and femoral osteotomies are frequently performed in patients with hip dysplasia. The aim of these surgeries are optimal biomechanical conditions of the hip joint thereby avoiding the occurrence of hip osteoarthritis or the delay of initial hip osteoarthritis progression. THERAPY: Nevertheless even with good biomechanical conditions of the hip joint, progression of hip osteoarthritis can be recognized postoperatively. A total hip arthroplasty is indicated even more after a time period with conservative treatment. In preparation for the operation, a detailed documentation of the initial clinical situation, appropriate imaging, implant selection and preoperative planning are mandatory. In addition, a biomechanical model representing the desired pre- and postoperative situation can be included in the preoperative planning. According to the previous osteotomy, the size and shape of the acetabulum after the osteotomy and the current pivot centre of the hip joint should be considered. Depending on these observations the acetabular cup can be directly inserted into the bone stock of the acetabulum or an acetabular plasty is necessary before implantation of the acetabular cup. With respect to the previous osteotomy of the femur, it needs to be clarified wether hardware removal will be necessary before total hip replacement; moreover, the anatomy of the proximal femur is critical. In addition, if necessary, a re-osteotomy of the femur is required to enable a hip stem implantation. CONCLUSION: Cementless total hip replacement should be preferred due to the younger patient age. The load of the hip replacement depends on the osseous anchoring and primary stability of the acetabular and femoral component. PMID- 27385387 TI - [Validation of the German version of the Oxford Elbow Score : A cross-sectional study]. AB - BACKGROUND: Elbow complaints are complex problems leading to severe consequences for affected people and the healthcare system. The German version of the Oxford Elbow Score (OES) is the first German-speaking instrument that specifically measures elbow complaints from the patient's perspective and changes of their health status. OBJECTIVE: The aim of this study is the validation of the German version of the OES. In this context the internal consistency and the construct validity were investigated. MATERIALS AND METHODS: 59 patients with elbow complaints completed the German version of the OES, the DASH and the SF-36 in a cross-sectional study. The internal consistency was calculated with Cronbach's alpha coefficients. Spearman's correlation coefficients were used to confirm construct validity. RESULTS: Cronbach's alpha for pain, function and psychological subscales was 0.88, 0.81 and 0.90, respectively. The whole questionnaire presents a Cronbach's alpha value of 0.93. Convergent construct validity was confirmed with correlation coefficients containing values of -0.84, 0.77 and -0.82 compared to DASH and values ranging from 0.41 to 0.80 compared with the physical domains of the SF-36. The divergent construct validity presented values ranging from 0.07 to 0.20 with the SF-36 domains of "general health perception" and "mental health". CONCLUSION: The German OES is an internal consistent instrument with good convergent and divergent construct validity. Other aspects of the validity, the reliability and the responsiveness should be confirmed through further studies. PMID- 27385388 TI - [Acetabuloplasty - The Dega and Pemberton technique]. AB - BACKGROUND: Hip dysplasia is the most common congenital deformity requiring surgical correction osteotomy in order to prevent early onset of secondary hip arthrosis. The shape of the acetabulum can be modified by Dega or Pemberton osteotomy and is indicated for hip dysplasia and luxation with irregularities of the socket for children aged between 2 and 12 when the y-physis is still open. METHOD: We will describe indication, contra-indication, preoperative planning as well as details of the Pemberton technique. In addition, we will provide practical advice based on our long-standing experience. RESULTS: We present long term results from the literature and also from our department. In addition, we will explain and critically discuss our own experiences and the risks and complications of surgical techniques. Good long-term results are reported for acetabuloplasties and Salter osteotomy which are preferred for surgical treatment of hip dysplasia in early life. Advantages and disadvantages of both surgical techniques will be compared in the discussion section. CONCLUSION: Dega and Pemberton acetabuloplasty shows good long-term results regarding prevention of a secondary coxarthrosis. However, correct indication is crucial since this surgical technique is more difficult compared to Salter osteotomy but is also associated with a higher correction potential and a lower complication rate. PMID- 27385389 TI - Quantified Pore-Scale Nanoparticle Transport in Porous Media and the Implications for Colloid Filtration Theory. AB - This study evaluates the pore-scale distribution of silver nanoparticles during transport through a sandy porous medium via quantitative synchrotron X-ray computed microtomography (qSXCMT). The associated distributions of nanoparticle flow velocities and mass flow rates were obtained by coupling these images with computational fluid dynamic (CFD) simulations. This allowed, for the first time, the comparison of nanoparticle mass flow with that assumed by the standard colloid filtration theory (CFT) modeling approach. It was found that (i) 25% of the pore space was further from the grain than assumed by the CFT model; (ii) the average pore velocity agreed well between results of the coupled qSXCMT/CFD approach and the CFT model within the model fluid envelope, although the former were 2 times larger than the latter in the centers of the larger pores and individual velocities were upwards of 20 times those in the CFT model at identical distances from grain surfaces ; and (iii) approximately 30% of all nanoparticle mass and 38% of all nanoparticle mass flow occurred further away from the grain surface than expected by the CFT model. This work suggests that a significantly smaller fraction of nanoparticles than expected will contact a grain surface by diffusion via CFT models, likely contributing to inadequate CFT model nanoparticle transport predictions. PMID- 27385390 TI - Comparative Evaluation of the Antimicrobial Efficacy of Three Immersion Chemical Disinfectants on Clinically Derived Poly(Vinyl Siloxane) Impressions. AB - PURPOSE: To comparatively evaluate the antimicrobial efficacy of freshly prepared electrolyzed oxidizing water (EOW) with that of 2.4% glutaraldehyde (GA) and 1% sodium hypochlorite (SH) on clinically derived poly vinyl siloxane (PVS) impressions. MATERIALS AND METHODS: Four clinically derived PVS impressions each were obtained from 10 subjects. One impression from each subject was randomly kept as control (group I), without disinfection. The remaining three impressions were randomly disinfected by immersion in either 2.4% GA (group II), 1% SH (group III), or freshly prepared EOW (group IV). The samples were subjected to microbial culture individually on brain heart infusion (BHI) agar medium. The organisms isolated were confirmed by visual examination and gram staining. Mean colony forming units (CFU) were counted, log10 reduction obtained and compared. Data were statistically analyzed using one-way ANOVA, followed by multiple comparisons using Tukey-HSD post hoc tests (p < 0.05). RESULTS: Streptococci, Staphylococci, Pseudomonas, Candida, Proteus, Klebsiella, and E. coli were isolated from all impressions including the controls, except those disinfected by EOW. All three disinfectants showed significant reduction in CFU and log10 reduction values as compared to the controls. EOW showed significantly higher reduction in log10 values compared to GA and SH, whereas GA and SH showed similar reductions. EOW, GA, and SH showed kill rates of 100%, 99.60%, and 99.82%, respectively. CONCLUSION: EOW showed significant antimicrobial efficacy as evidenced by reduction in log10 values when used as an immersion disinfectant for PVS impressions when compared with the results obtained using GA and SH. These results need further investigation. CLINICAL IMPLICATIONS: EOW shows high antimicrobial efficacy when used as an immersion disinfectant as compared to GA and SH for clinically derived PVS impressions. PMID- 27385391 TI - Cross-Validation of Two Commonly Used Self-Stigma Measures, Taiwan Versions of the Internalized Stigma Mental Illness Scale and Self-Stigma Scale-Short, for People With Mental Illness. AB - Self-stigma instruments investigate how people with mental illness internalize public stigma. However, information is limited for the psychometric properties of their scores, especially cross-validating scores from different instruments. Thus, we used confirmatory factor analyses (CFAs) and item-response theory (IRT) models to examine the Internalized Stigma Mental Illness (ISMI) scale and the Self-Stigma Scale-Short (SSS-S). Participants with mental illness ( n = 347) completed both instruments. The CFAs that simultaneously accounted for both the instrument (ISMI and SSS-S) and the trait (Affect, Cognitive, and Behavior concepts) effects outperformed those that accounted only for the instrument effect or only the trait effect. All item scores fit the IRT model and were fit with ordered, progressing hierarchies in their step difficulties. We conclude that both instruments are feasible for measuring the self-stigma and that future research can combine the items of both. PMID- 27385392 TI - Image guided portal vein access techniques in TIPS creation and considerations regarding their use. AB - Transjugular intrahepatic portosystemic shunt (TIPS) is a difficult procedure to perform and accessing the portal vein is a very challenging step. There are three broad categories of image guided TIPS creation techniques. Each technique has its advantages and disadvantages. TIPS procedure carries some risk of complications regardless of the guidance technique employed. The technology for TIPS has evolved in parallel with the expanding indications for TIPS. Ultrasound guidance technique offers a safe option, particularly for patients with challenging anatomy. Patient safety should always come first and the US guided technique should be more routinely used. Experience is the main factor in the success of TIPS. Other factors to consider in reducing the all-cause morbidity and mortality are patient selection, patient management and the clinical setting. PMID- 27385393 TI - Lipid emulsion layering in extracorporeal membrane oxygenation circuit. PMID- 27385394 TI - Human metapneumovirus in lung transplant recipients: characteristics and outcomes. AB - Human metapneumovirus (hMPV) causes serious respiratory tract infections in lung transplant recipients (LTRs). We evaluated the characteristics and adverse drug reactions (ADR) of oral ribavirin therapy for hMPV infections in LTRs. LTRs with respiratory symptoms or suspected infection of unknown origin were routinely sampled with nasopharyngeal swabs (NPS) for virological and bacteriological analysis as part of a diagnostic workup. Medical records of hMPV polymerase chain reaction (PCR)-positive LTRs at the University Hospital of Zurich were reviewed retrospectively. Between January 2012 and June 2014, 12 (80%) of 15 consecutive patients with documented hMPV infection received oral ribavirin therapy (800 mg/d, after 48 h: 400 mg/d). Mean duration of therapy was 28.6 days (range: 11 54). Mean duration of viral shedding was 16.3 days (range: 5-48). In general, oral ribavirin was well tolerated in LTRs. The most common ADR was moderate anaemia. All patients recovered from infection without immediate serious sequelae within 3 months of infection. PMID- 27385395 TI - Monitoring of kidney function in elderly HIV-positive patients. PMID- 27385397 TI - Visible Light Photocatalytic Radical-Radical Cross-Coupling Reactions of Amines and Carbonyls: A Route to 1,2-Amino Alcohols. AB - An intermolecular radical-radical cross-coupling reaction of secondary and tertiary amines with aryl ketones and aldehydes has been developed using visible light photoredox catalysis. This reaction provides an efficient and straightforward approach to some useful 1,2-amino alcohols in moderate to good yields under mild conditions. PMID- 27385396 TI - Altered redox mitochondrial biology in the neurodegenerative disorder fragile X tremor/ataxia syndrome: use of antioxidants in precision medicine. AB - A 55-200 expansion of the CGG nucleotide repeat in the 5'-UTR of the fragile X mental retardation 1 gene (FMR1) is the hallmark of the triplet nucleotide disease known as the "premutation" as opposed to those with >200 repeats, known as the full mutation or fragile X syndrome. Originally, premutation carriers were thought to be free of phenotypic traits; however, some are diagnosed with emotional and neurocognitive issues and, later in life, with the neurodegenerative disease fragile X-associated tremor/ataxia syndrome (FXTAS). Considering that mitochondrial dysfunction has been observed in fibroblasts and post-mortem brain samples from carriers of the premutation, we hypothesized that mitochondrial dysfunction-derived ROS may result in cumulative oxidative nitrative damage. Fibroblasts from premutation carriers (n=31, all FXTAS-free except 8), compared to age- and sex-matched controls (n=25), showed increased mitochondrial ROS production, impaired Complex I activity, lower expression of MIA40 (rate-limiting step of the redox-regulated mitochondrial-disulfide-relay system), increased mtDNA deletions, and increased biomarkers of lipid and protein oxidative-nitrative damage. Most of the outcomes were more pronounced in FXTAS affected individuals. Significant recovery of mitochondrial mass and/or function was obtained with superoxide or hydroxyl radicals' scavengers, a glutathione peroxidase analog, or by overexpressing MIA40. The effects of ethanol (a hydroxyl radical scavenger) were deleterious, while others (by N-acetyl-cysteine, quercetin and epigallocatechin-3-gallate) were outcome- and/or carrier-specifics. The use of antioxidants in the context of precision medicine is discussed with the goal of improving mitochondrial function in carriers with the potential of decreasing the morbidity and/or delaying FXTAS onset. PMID- 27385398 TI - Impact of comorbidity and anemia in patients with oropharyngeal cancer primarily treated with surgery in the human papillomavirus era. AB - BACKGROUND: Comorbidity and anemia strongly influence treatment and outcome of oropharyngeal squamous cell carcinomas (SCCs), but respective data are frequently lacking in clinical studies. We evaluated 149 cases of oropharyngeal SCC primarily treated with surgery regarding the impact of these factors on disease free survival (DFS) and overall survival (OS). METHODS: Data were recorded during treatment and follow-up visits. Human papillomavirus (HPV) association of oropharyngeal SCC was detected by p16 immunohistochemistry. RESULTS: Patients with p16-positive disease were significantly less comorbid and anemic, and treated more aggressively. Comorbidity and anemia, but not p16 status, significantly influenced DFS and had more impact on OS than p16 status. CONCLUSION: In our study, p16-positive seems a good surrogate marker for healthier patients. Patients with p16-positive disease showed improved survival, but this was limited to none/mild comorbid and/or nonanemic individuals in this group. On the basis of our results, we strongly suggest the inclusion of these factors in risk stratification for clinical studies. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 7-16, 2017. PMID- 27385399 TI - Rhodium/Yanphos-Catalyzed Asymmetric Interrupted Intramolecular Hydroaminomethylation of trans-1,2-Disubstituted Alkenes. AB - The first interrupted asymmetric hydroaminomethylation reaction was developed. The challenging trans-1,2-disubstituted olefins were employed as substrates, and a series of valuable chiral pyrrolidinones and pyrrolidines were obtained in high yields with high regioselectivities and excellent enantioselectivities. Several synthetic transformations were conducted, demonstrating the high synthetic utility of our method. A creative route for the synthesis of vernakalant and Enablex was also developed. PMID- 27385400 TI - Effect of Standardised Scoring Conventions on Inter-rater Reliability in the Endoscopic Evaluation of Crohn's Disease. AB - BACKGROUND AND AIMS: The Crohn's Disease Endoscopic Index of Severity [CDEIS] and Simplified Endoscopic Score for Crohn's Disease [SES-CD] demonstrate consistent overall intra- and inter-rater reliability. However, the reliability of some index items is relatively poor. We evaluated scoring conventions to improve the reliability of these items. METHODS: Five gastroenterologists with no previous experience scoring the CDEIS or SES-CD were trained on their use. A total of 65 video recordings of colonoscopies were scored blindly by each gastroenterologist before and after additional training on index scoring conventions. Intra-class correlation coefficients [ICCs] assessed the effect of application of these conventions on the reliability of the CDEIS, SES-CD, and a Global Evaluation of Lesion Severity [GELS] score. RESULTS: Following training on scoring conventions, inter-rater ICCs (95% confidence interval [CI]) for the total SES-CD score increased from 0.78 [0.71, 0.85] to 0.85 [0.79, 0.89]. The ICCs for the total CDEIS and GELS scores were not affected: corresponding inter-rater ICCs were 0.74 [0.65, 0.81] and 0.49, [0.38, 0.61] before and 0.73 [0.65, 0.81] and 0.53 [0.42, 0.64] following application of scoring conventions. Estimations of ulcer depth, surface area, anatomical location, and stenosis were important sources of variability. CONCLUSIONS: Use of scoring conventions previously developed by expert central readers enhanced the reliability of the SES-CD but did not similarly affect the CDEIS or GELS. As the SES-CD is more likely to be reliable than the CDEIS and can be optimised with targeted training, it is the preferred instrument for use in clinical trials. PMID- 27385401 TI - A Pitfall to Avoid: Hyperlipasemia, Azathioprine, and Autoimmune Pancreatitis. PMID- 27385403 TI - Raman-based noninvasive metabolic profile evaluation of in vitro bovine embryos. AB - The timing of the first embryonic cell divisions may predict the ability of an embryo to establish pregnancy. Similarly, metabolic profiles may be markers of embryonic viability. However, in bovine, data about the metabolomics profile of these embryos are still not available. In the present work, we describe Raman based metabolomic profiles of culture media of bovine embryos with different developmental kinetics (fast x slow) throughout the in vitro culture. The principal component analysis enabled us to classify embryos with different developmental kinetics since they presented specific spectroscopic profiles for each evaluated time point. We noticed that bands at 1076 cm(-1) (lipids), 1300 cm(-1) (Amide III), and 2719 cm(-1) (DNA nitrogen bases) gave the most relevant spectral features, enabling the separation between fast and slow groups. Bands at 1001 cm(-1) (phenylalanine) and 2892 cm(-1) (methylene group of the polymethylene chain) presented specific patterns related to embryonic stage and can be considered as biomarkers of embryonic development by Raman spectroscopy. The culture media analysis by Raman spectroscopy proved to be a simple and sensitive technique that can be applied with high efficiency to characterize the profiles of in vitro produced bovine embryos with different development kinetics and different stages of development. PMID- 27385402 TI - COG lobe B sub-complex engages v-SNARE GS15 and functions via regulated interaction with lobe A sub-complex. AB - The conserved oligomeric Golgi (COG) complex is a peripheral membrane protein complex which orchestrates tethering of intra-Golgi vesicles. We found that COG1 4 (lobe A) and 5-8 (lobe B) protein assemblies are present as independent sub complexes on cell membranes. Super-resolution microscopy demonstrates that COG sub-complexes are spatially separated on the Golgi with lobe A preferential localization on Golgi stacks and the presence of lobe B on vesicle-like structures, where it physically interacts with v-SNARE GS15. The localization and specific interaction of the COG sub-complexes with the components of vesicle tethering/fusion machinery suggests their different roles in the vesicle tethering cycle. We propose and test a novel model that employs association/disassociation of COG sub-complexes as a mechanism that directs vesicle tethering at Golgi membranes. We demonstrate that defective COG assembly or restriction of tethering complex disassembly by a covalent COG1-COG8 linkage is inhibitory to COG complex activity, supporting the model. PMID- 27385404 TI - Improving Screening Mammography Outcomes Through Comparison With Multiple Prior Mammograms. AB - OBJECTIVE: The objective of the present study is to evaluate the effect of comparison with multiple prior mammograms on the outcomes of screening mammography relative to comparison with a single prior mammogram. MATERIALS AND METHODS: We retrospectively analyzed 46,288 consecutive screening mammograms performed at our institution for 22,792 women. We divided these examinations into three groups: those interpreted without comparison with prior mammograms, those interpreted in comparison with one prior examination, and those interpreted in comparison with two or more prior examinations. For each group, we determined the rate of examination recall. We also calculated the positive predictive value of recall (i.e., positive predictive value level 1 [PPV1]) and the cancer detection rate (CDR) for both the group of examinations compared with a single prior mammogram and the group compared with multiple prior mammograms. Generalized estimating equations with the logistic link function were used to determine the relative odds ratio of recall as a function of the number of comparisons, with adjustment made for age as a confounding variable. The Fisher exact test was performed to compare the PPV1 and the CDR in the different cohorts. RESULTS: The recall rate for mammograms interpreted without comparison with prior examinations was 16.6%, whereas that for mammograms compared with one prior examination was 7.8% and that for mammograms compared with two or more prior examinations was 6.3%. After adjustment was made for age, the odds ratio of recall for the group with multiple prior examinations relative to the group with a single prior examination was 0.864 (95% CI, 0.776-0.962; p = 0.0074). Statistically significant increases in the PPV1 of 0.05 (p = 0.0009) and in the CDR of 2.3 cases per 1000 examinations (p = 0.0481) were also noted for mammograms compared with multiple prior examinations relative to those compared with a single prior examination. CONCLUSION: Comparison with two or more prior mammograms resulted in a statistically significant reduction in the screening mammography recall rate and increases in the CDR and PPV1 relative to comparison with a single prior mammogram. PMID- 27385406 TI - Use of spirometry among chest physicians and primary care physicians in India. AB - Although spirometry is the gold-standard diagnostic test for obstructive airways diseases, it remains poorly utilised in clinical practice. We aimed to investigate the use of spirometry across India, the change in its usage over a period of time and to understand the reasons for its under-utilisation. Two nationwide surveys were conducted in the years 2005 and 2013, among four groups of doctors: chest physicians (CPs), general physicians (GenPs), general practitioners (GPs) and paediatricians (Ps). A total of 1,000 physicians from each of the four groups were randomly selected from our database in the years 2005 and 2013. These surveys were conducted in 52 cities and towns across 15 states in India. A questionnaire was administered to the physicians, which captured information about their demographic details, type of practice and use of spirometry. The overall response rates of the physicians in 2005 and 2013 were 42.8% and 54.9%, respectively. Spirometry was reported to be used by 55% CPs, 20% GenPs, 10% GPs and 5% Ps in 2005, and this increased by 30.9% among CPs (P value <0.01), 18% among GenPs (P value=0.01), 20% among GPs (P value: not significant) and 224% among Ps (P value <0.01). The reasons for not using spirometry varied between 2005 and 2013. In all, 32.2% of physicians were unaware of which predicted equation they were using. The use of spirometry in India is low, although it seems to have improved over the years. The reasons identified in this study for under-utilisation should be used to address initiatives to improve the use of spirometry in clinical practice. PMID- 27385405 TI - Ac-Trp-DPhe(p-I)-Arg-Trp-NH2, a 250-Fold Selective Melanocortin-4 Receptor (MC4R) Antagonist over the Melanocortin-3 Receptor (MC3R), Affects Energy Homeostasis in Male and Female Mice Differently. AB - The melanocortin-4 receptor (MC4R) has been indicated as a therapeutic target for metabolic disorders such as anorexia, cachexia, and obesity. The current study investigates the in vivo effects on energy homeostasis of a 15 nM MC4R antagonist SKY2-23-7, Ac-Trp-DPhe(p-I)-Arg-Trp-NH2, that is a 3700 nM melanocortin-3 receptor (MC3R) antagonist with minimal MC3R and MC4R agonist activity. When monitoring both male and female mice in TSE metabolic cages, sex-specific responses were observed in food intake, respiratory exchange ratio (RER), and energy expenditure. A 7.5 nmol dose of SKY2-23-7 increased food intake, increased RER, and trended toward decreasing energy expenditure in male mice. However, this compound had minimal effect on female mice's food intake and RER at the 7.5 nmol dose. A 2.5 nmol dose of SKY2-23-7 significantly increased female food intake, RER, and energy expenditure while having a minimal effect on male mice at this dose. The observed sex differences of SKY2-23-7 administration result in the discovery of a novel chemical probe for elucidating the molecular mechanisms of the sexual dimorphism present within the melanocortin pathway. To further explore the melanocortin sexual dimorphism, hypothalamic gene expression was examined. The mRNA expression of the MC3R and proopiomelanocortin (POMC) were not significantly different between sexes. However, the expression of agouti-related peptide (AGRP) was significantly higher in female mice which may be a possible mechanism for the sex-specific effects observed with SKY2-23-7. PMID- 27385407 TI - Effects of Balloon Pulmonary Valvuloplasty as Preoperative Palliation for Tetralogy of Fallot. AB - OBJECTIVES: We investigated the effect of balloon pulmonary valvuloplasty (BPV) as a palliative procedure for patients with tetralogy of Fallot (TOF). METHODS: This was a retrospective single-center study conducted between 2008 and 2014. We classified patients into three groups according to palliation: treatment with BPV (group I), with a Blalock-Taussig shunt (group II), and with infundibulectomy (group III). The growth of the pulmonary valve (PV) annulus and need for transannular patching (TAP) during total correction were compared between groups. RESULTS: Forty-eight patients were enrolled: 31, 10, and 7 in groups I, II, and III, respectively. The mean ages at palliation were 26.3 +/- 23.6, 21.5 +/- 16.4, and 15.2 +/- 4.2 days in groups I, II, and III, respectively (P = .867). The success rate of BPV was 90.3%. The initial PV z-score before palliation did not differ between groups I, II, and III (-3.14 +/- 1.44, -3.84 +/- 1.47, and -3.71 +/- 1.68; P = .494); the preoperative PV z-score before total correction was larger in group I than in group II (-1.19 +/- 1.14 and -3.05 +/- 1.19; P = .001), and also larger in group III than in group II (group III: -1.10 +/- 0.90; P = .003). The change in pulse oxygen saturation differed significantly between the three groups (P = .031), particularly between groups I and II (P = .010), and the change in PV z-score was greater in groups I and III than in group II (P < .001). TAP during total correction was performed in 29.0%, 90.0%, and 16.7% of groups I, II, and III, respectively (P = .001; group I vs. II, P = .001; group II vs. III, P = .008). CONCLUSION: BPV was an effective and safe palliation that increased pulmonary blood flow and promoted growth of the PV annulus in selected symptomatic newborns with TOF. PMID- 27385408 TI - Comorbidity burden is not associated with higher mortality after out-of-hospital cardiac arrest. AB - OBJECTIVES: We investigated whether comorbidity burden of comatose survivors of out-of-hospital cardiac arrest (OHCA) affects outcome and if comorbidity modifies the effect of target temperature management (TTM) on final outcome. DESIGN: The TTM trial randomized 939 patients to 24 h of TTM at either 33 or 36 degrees C with no difference regarding mortality and neurological outcome. This post-hoc study of the TTM-trial formed a modified comorbidity index (mCI), based on available comorbidities from the Charlson comorbidity index (CCI). RESULTS: Bystander cardiopulmonary resuscitation (CPR) decreased with higher comorbidity group, p = 0.01. Comorbidity groups were univariately associated with higher mortality compared to mCI0 (HRmCI1: 1.55, CI: 1.25-1.93, p < 0.001, HRmCI2: 2.01, CI: 1.55-2.62, p < 0.001, HRmCI >= 3: 2.16, CI: 1.57-2.97, p < 0.001). When adjusting for confounders there was a consistent, nonsignificant association between level of comorbidity and mortality (HRmC11: 1.17, CI: 0.92-1.48, p = 0.21, HRmCI2: 1.28, CI: 0.96-1.71, p = 0.10, HRmCI >= 3: 1.37, CI: 0.97-1.95, p = 0.08). There was no interaction between comorbidity burden and level of TTM on outcome, p = 0.61. CONCLUSION: Comorbidity burden was associated with higher mortality following OHCA, but when adjusting for confounders, the influence was no longer significant. The association between mCI and mortality was not modified by TTM. Comorbidity burden is associated with lower rates of bystander cardiopulmonary resuscitation after OHCA. PMID- 27385409 TI - Polypeptides from the Skin of Rana chensinensis Exert the Antioxidant and Antiapoptotic Activities on HaCaT Cells. AB - Studies have shown that frog skin secretes many types of peptides that are good for human skin. In this study, acid and enzymatic extracts of Rana skin peptides (acid/enzymatic Rana skin peptides, ARPs/ERPs) were obtained. The chemical and physical properties of the ARPs and ERPs were identified through UV scanning, HGLC, FRIT, and MS. MTS and flow cytometry were used to test the proproliferative and antiapoptotic effects of the ARPs and ERPs on human immortalized keratinocytes (HaCaT cells). To elucidate the antiapoptotic mechanisms, the mRNA and protein levels of EGF (epidermal growth factor, which enhances stimulation of cellular proliferation in both cells and epithelial tissues) and caspase-3 were evaluated using quantitative RT-PCR. The results indicated that the ARPs and ERPs were extracted from the Rana skin with yields of 0.65% and 0.52%, respectively. Treatment with ARPs (1.6 g/L) and ERPs (0.8 g/L) showed a 1.66-fold (p < 0.001) and 2.1-fold (p < 0.001) enhancement in the proliferation rates of HaCaT cells. The rate of apoptosis decreased by 2.6 fold (p < 0.01) and 3.4 fold (p < 0.01) under the UVB stimulation, respectively, at the same time, the up-regulation of EGF and down-regulation of caspase-3 were found. These results suggested that we can dig into the potential value of ARPs/ERPs in a new field. PMID- 27385411 TI - Promoting Accurate Variability of Social Skills in Children With Autism Spectrum Disorder. AB - Restricted and repetitive behavior is a central feature of autism spectrum disorder (ASD), with such behaviors often resulting in lack of reinforcement in social contexts. The present study investigated training multiple exemplars of target behaviors and the utilization of lag schedules of reinforcement in the context of social skills training to promote appropriate and varied social behavior in children with ASD. Five participants with ASD between the ages of 7 and 9 attended a twice-weekly social skills group for 8 weeks. A multiple probe design across skills was utilized to assess intervention effects. During baseline, participants demonstrated low levels of skill accuracy and low appropriate variability in responding. During continuous reinforcement with one trained exemplar, skill accuracy increased while appropriate variability remained low. Training of three exemplars of target skills resulted in minimal improvements in appropriate variability. Introduction of a Lag 2 schedule with three trained exemplars was generally associated with increased appropriate variability. Further appropriate variability was observed during Lag 4 with three trained exemplars. Limitations and implications are discussed. PMID- 27385410 TI - Application of an in vitro-amplification assay as a novel pre-screening test for compounds inhibiting the aggregation of prion protein scrapie. AB - In vitro amplification assays, such as real-time quaking-induced conversion (RT QuIC) are used to detect aggregation activity of misfolded prion protein (PrP) in brain, cerebrospinal fluid (CSF) and urine samples from patients with a prion disease. We believe that the method also has a much broader application spectrum. In the present study, we applied RT-QuIC as a pre-screening test for substances that potentially inhibit the aggregation process of the cellular PrP (PrP(C)) to proteinase (PK)-resistant PrP(res). We chose doxycycline as the test substance as it has been tested successfully in animal models and proposed in clinical studies as a therapeutic for prion diseases. The RT-QuIC-reaction was seeded with brain tissue or CSF from sCJD patients and doxycycline was then added in different concentrations as well as at different time points. In both experiments, we observed a dose- and time-dependent inhibition of the RT-QuIC seeding response and a decrease of PK resistant PrP(res) when doxycycline was added. In contrast, ampicillin or sucrose had no effect on the RT-QuIC seeding response. Our study is the first to apply RT-QuIC as a pre-screening assay for compounds inhibiting the PrP aggregation in vitro and confirms that doxycycline is an efficient inhibitor of the PrP aggregation process in RT-QuIC analysis. PMID- 27385412 TI - Predictors of Dropout From Cognitive-Behavioral Group Treatment for Panic Disorder With Agoraphobia: An Exploratory Study. AB - Panic disorder and agoraphobia are both characterized by avoidance behaviors, which are known correlates of treatment discontinuation. The aim of this exploratory study is to distinguish the profile of participants suffering from panic disorder with agoraphobia that complete treatment from those who discontinue therapy by assessing four categories of predictor variables: the severity of the disorder, sociodemographic variables, participants' expectations, and dyadic adjustment. The sample included 77 individuals diagnosed with panic disorder with agoraphobia who completed a series of questionnaires and participated in a cognitive-behavioral group therapy consisting of 14 weekly sessions. Hierarchical linear regression analyses revealed the importance of anxiety, prognosis, and role expectations as well as some individual variables as predictors of therapeutic dropout, either before or during treatment. Among the most common reasons given by the 29 participants who discontinued therapy were scheduling conflicts, dissatisfaction with treatment, and conflicts with their marital partner. These results suggest that expectations and dyadic relationships have an impact on therapeutic discontinuation. The clinical implications of these findings are discussed. PMID- 27385413 TI - Inferring phylogeny and speciation of Gymnosporangium species, and their coevolution with host plants. AB - Gymnosporangium species (Pucciniaceae, Pucciniales) cause serious diseases and significant economic losses to apple cultivars. Most of the reported species are heteroecious and complete their life cycles on two different plant hosts belonging to two unrelated genera, i.e. Juniperus and Malus. However, the phylogenetic relationships among Gymnosporangium species and the evolutionary history of Gymnosporangium on its aecial and telial hosts were still undetermined. In this study, we recognized species based on rDNA sequence data by using coalescent method of generalized mixed Yule-coalescent (GMYC) and Poisson Tree Processes (PTP) models. The evolutionary relationships of Gymnosporangium species and their hosts were investigated by comparing the cophylogenetic analyses of Gymnosporangium species with Malus species and Juniperus species, respectively. The concordant results of GMYC and PTP analyses recognized 14 species including 12 known species and two undescribed species. In addition, host alternations of 10 Gymnosporangium species were uncovered by linking the derived sequences between their aecial and telial stages. This study revealed the evolutionary process of Gymnosporangium species, and clarified that the aecial hosts played more important roles than telial hosts in the speciation of Gymnosporangium species. Host switch, losses, duplication and failure to divergence all contributed to the speciation of Gymnosporangium species. PMID- 27385415 TI - Hispidulin alleviated methamphetamine-induced hyperlocomotion by acting at alpha6 subunit-containing GABAA receptors in the cerebellum. AB - RATIONALE: Hispidulin is a flavonoid we isolated from Clerodendrum inerme, an herb that effectively remitted a case of intractable motor tic disorders. Hispidulin was shown to be a positive allosteric modulator (PAM) of GABAA receptors, including the alpha6 subunit-containing subtype (alpha6GABAAR) that is predominantly expressed in cerebellar granule cells and insensitive to diazepam. OBJECTIVES: We explored the action mechanism(s) of hispidulin using hyperdopaminergic mouse models induced by methamphetamine and apomorphine, based on the hyperdopaminergic nature of tic disorders. RESULTS: Hispidulin significantly inhibited methamphetamine-induced hyperlocomotion (MIH) at i.p. doses without affecting apomorphine-induced hyperlocomotion and stereotypy behaviors or having significant benzodiazepine-like effects (BZLE), including sedation, anxiety, and motor impairment. When given by intracerebellar (i.c.b.) microinjection, hispidulin also alleviated MIH and this effect was prevented by i.c.b. coadministration of furosemide, an alpha6GABAAR antagonist, and mimicked by i.c.b. Ro 15-4513, an alpha6GABAAR PAM. Conversely, i.c.b. diazepam did not affect MIH while it reduced MIH at i.p. doses having significant BZLE. In a screening assay for 92 neurotransmitter receptors/degradation enzymes/transporters, hispidulin displayed significant (>50 % inhibition of radiolabeled ligand binding at 10 MUM) binding affinity only at the benzodiazepine binding site of GABAARs (IC50 0.73~1.78 MUM) and catecholamine-o methyl-transferase (COMT) (IC50 1.32 MUM). OR-486, a more potent COMT inhibitor than hispidulin, did not affect MIH. CONCLUSIONS: It is suggested that hispidulin alleviates MIH via acting as a PAM of cerebellar alpha6GABAARs, but not through COMT inhibition or affecting dopamine receptor responsiveness. Thus, selective alpha6GABAAR PAMs may have the potential to be a novel treatment for hyperdopaminergic disorders. PMID- 27385416 TI - Alterations in alpha5* nicotinic acetylcholine receptors result in midbrain- and hippocampus-dependent behavioural and neural impairments. AB - RATIONALE: Evidence links alterations in alpha5-containing nicotinic receptors (alpha5*-nAChRs) to nicotine addiction. Notably, the rs16969968 polymorphism in the alpha5 gene (alpha5SNP) increases the risk for heavy smoking and impairs nicotine-rewarding properties in mice. Additional work is needed to understand how native and polymorphic alpha5*-nAChRs contribute to processes associated with the risk for nicotine addiction. OBJECTIVES: We aimed at understanding the contribution of alpha5*-nAChRs to endophenotypes like increased responses to novelty and anxiety, known to promote vulnerability to addiction, and to the response of the dopamine and serotonin systems to nicotine. METHODS: Behavioural phenotypes were investigated in mice lacking the alpha5 gene (alpha5(-/-)). Nicotine injections were performed to test the consequences of nicotine exposure on the phenotypes identified. Dopamine and serotonin signalling were assessed using in vivo microdialysis and electrophysiology. We used lentiviral vectors to compare the consequences of re-expressing either the alpha5 wild-type allele or the alpha5SNP in specific brain areas of alpha5(-/-) mice. RESULTS: alpha5(-/-) mice did not exhibit high responses to novelty but showed decreased novelty induced rearing behaviour together with high anxiety. Exposure to high doses of nicotine rescued these phenotypes. We identified altered spontaneous and nicotine elicited serotonin and dopamine activity in alpha5(-/-) mice. Re-expression of alpha5 in the ventral tegmental area and hippocampus rescued rearing and anxiety levels in alpha5(-/-) mice, respectively. When expressing the alpha5SNP instead, this resulted in a knockout-like phenotype for both behaviours. CONCLUSIONS: We propose that altered alpha5*-nAChR cholinergic signalling contributes to emotional/behavioural impairments that may be alleviated by nicotine consumption. PMID- 27385418 TI - Efficacy of sutureless aortic valves in minimally invasive cardiac surgery: an evolution of the surgical technique. AB - BACKGROUND: Sutureless aortic valve prostheses have the potential of shortening surgical time, but if this results in improved clinical outcome remains to be determined. The aim of this study was to compare the outcome of patients undergoing conventional vs. minimally invasive AVR, with either a stented or sutureless bioprosthesis. METHODS: From 2007 to 2015, 627 patients underwent elective isolated AVR and were divided into three groups: patients who underwent sutureless-AVR via J sternotomy (group A, N.=206) and patients who underwent stented-AVR via J sternotomy (group B, N.=247) or full-sternotomy (group C, N.=174). RESULTS: Patients in group A were significantly older than groups B and C (77+/-5 vs. 74+/-7 and 70+/-8 years; P<0.001). Aortic cross-clamp and cardiopulmonary bypass times were shorter in group A than in groups B and C. As expected, aortic cross-clamp time was prolonged in group B as compared to groups A and C (60+/-18 vs. 36+/-10 and 54+/-16 min; P<0.001). After multivariate adjustment, minimally invasive AVR resulted in significantly fewer postoperative complications in terms of drainage bleeding and the need for blood transfusions (385+/-287 vs. 500+/-338 mL, P=0.006; and 1.3+/-2.1 vs. 1.8+/-2.6 IU, P=0.001, respectively). No differences in postoperative outcomes were observed among groups. CONCLUSIONS: The minimally invasive approach confers a protective effect against bleeding complications, but it is time-consuming. The use of sutureless valves is associated with significantly shorter surgical times compared with stented bioprostheses. In addition, no differences in mortality were observed among groups, and patients who received a sutureless valve, though significantly older, showed a better clinical outcome than patients who received a stented valve. PMID- 27385417 TI - Antidepressant-like effects of standardized gypenosides: involvement of brain derived neurotrophic factor signaling in hippocampus. AB - RATIONALE: Gypenosides have been reported to produce neuroprotective effects and increase monoamine neurotransmitter levels in the brain. OBJECTIVE: Considering that depression is involved in monoamine reduction, this study evaluated the antidepressant-like effects of gypenosides in mice exposed to chronic unpredictable mild stress (CUMS). METHODS: The sucrose preference test and forced swimming test were performed after administration of gypenosides (at 25, 50, or 100 mg/kg) for 4 weeks. Hippocampal brain-derived neurotrophic factor (BDNF) and its downstream targets were analyzed by western blot. Additionally, hippocampal neuronal proliferation was measured by immunohistochemistry. RESULTS: Four-week treatment with fluoxetine (20 mg/kg) and gypenosides (at either 50 or 100 mg/kg) increased sucrose preference and decreased the immobility time in mice exposed to CUMS. In addition, gypenosides (at either 50 or 100 mg/kg) also increased BDNF expression and neuronal proliferation in the hippocampus of CUMS animals. Further, we showed that treating CUMS mice with K252a, which is an inhibitor of the BDNF receptor TrkB, blocked the effects of gypenosides (100 mg/kg), including behavioral improvements, neuronal proliferation, and up-regulation of p-TrkB, p ERK, and p-Akt proteins. CONCLUSIONS: This study demonstrates that gypenosides exhibit antidepressant-like effects in mice, which may be mediated by activation of the BDNF-ERK/Akt signaling pathway in the hippocampus. PMID- 27385419 TI - Cold-adapted influenza viruses as a promising platform for viral-vector vaccines. PMID- 27385420 TI - Sieve estimation of Cox models with latent structures. AB - This article considers sieve estimation in the Cox model with an unknown regression structure based on right-censored data. We propose a semiparametric pursuit method to simultaneously identify and estimate linear and nonparametric covariate effects based on B-spline expansions through a penalized group selection method with concave penalties. We show that the estimators of the linear effects and the nonparametric component are consistent. Furthermore, we establish the asymptotic normality of the estimator of the linear effects. To compute the proposed estimators, we develop a modified blockwise majorization descent algorithm that is efficient and easy to implement. Simulation studies demonstrate that the proposed method performs well in finite sample situations. We also use the primary biliary cirrhosis data to illustrate its application. PMID- 27385421 TI - Electroactive biomimetic collagen-silver nanowire composite scaffolds. AB - Electroactive biomaterials are widely explored as bioelectrodes and as scaffolds for neural and cardiac regeneration. Most electrodes and conductive scaffolds for tissue regeneration are based on synthetic materials that have limited biocompatibility and often display large discrepancies in mechanical properties with the surrounding tissue causing problems during tissue integration and regeneration. This work shows the development of a biomimetic nanocomposite material prepared from self-assembled collagen fibrils and silver nanowires (AgNW). Despite consisting of mostly type I collagen fibrils, the homogeneously embedded AgNWs provide these materials with a charge storage capacity of about 2.3 mC cm(-2) and a charge injection capacity of 0.3 mC cm(-2), which is on par with bioelectrodes used in the clinic. The mechanical properties of the materials are similar to soft tissues with a dynamic elastic modulus within the lower kPa range. The nanocomposites also support proliferation of embryonic cardiomyocytes while inhibiting the growth of both Gram-negative Escherichia coli and Gram positive Staphylococcus epidermidis. The developed collagen/AgNW composites thus represent a highly attractive bioelectrode and scaffold material for a wide range of biomedical applications. PMID- 27385422 TI - Small-Molecule Carbohydrate-Based Immunostimulants. AB - In this review, we discuss small-molecule, carbohydrate-based immunostimulants that target Toll-like receptor 4 (TLR-4) and cluster of differentiation 1D (CD1d) receptors. The design and use of these molecules in immunotherapy as well as results from their use in clinical trials are described. How these molecules work and their utilization as vaccine adjuvants are also discussed. Future applications and extensions for the use of these analogues as therapeutic agents will be outlined. PMID- 27385423 TI - "Ene" Reactions of Singlet Oxygen at the Air-Water Interface. AB - Prenylsurfactants [(CH3)2C?CH(CH2)nSO3(-) Na(+) (n = 4, 6, or 8)] were designed to probe the "ene" reaction mechanism of singlet oxygen at the air-water interface. Increasing the number of carbon atoms in the hydrophobic chain caused an increase in the regioselectivity for a secondary rather than tertiary surfactant hydroperoxide, arguing for an orthogonal alkene on water. The use of water, deuterium oxide, and H2O/D2O mixtures helped to distinguish mechanistic alternatives to homogeneous solution conditions that include dewetting of the pi bond and an unsymmetrical perepoxide transition state in the hydroperoxide forming step. The prenylsurfactants and a photoreactor technique allowed a certain degree of interfacial control of the hydroperoxidation reaction on a liquid support, where the oxidant (airborne (1)O2) is delivered as a gas. PMID- 27385424 TI - Identification of the Mtus1 Splice Variant as a Novel Inhibitory Factor Against Cardiac Hypertrophy. AB - BACKGROUND: In cardiac hypertrophy and failure, there is a widespread alteration in mRNA splicing, but the role of splice variants in cardiac hypertrophy has not yet been fully elucidated. In this study, we used an exon array to identify novel splice variants associated with cardiac hypertrophy. METHODS AND RESULTS: We performed genome-wide exon array analysis and developed a splicing profile in murine hearts with hypertrophy induced by transverse aortic constriction for 8 weeks. Following global analysis of splice variants using the Mouse Exon 1.0 ST Array, we identified 46 spliced genes and narrowed our focus to 1 gene, mitochondrial tumor suppressor 1 (Mtus1), whose splice variants were registered in the NCBI RefSeq database. Notably, one of the splice variants Mtus1A was specifically upregulated, although the total expression of the Mtus1 gene remained unchanged. We showed that Mtus1A was localized in the mitochondria, and its expression level increased with the degree of cardiac hypertrophy. In cultured cardiomyocytes, Mtus1A overexpression reduced phenylephrine-induced reactive oxygen species production and consequent ERK phosphorylation, resulting in a decrease in both cell size and protein synthesis. In vivo, cardiac-specific Mtus1A transgenic mice showed left ventricle wall thinning and a reduced hypertrophic response to pressure overload and phenylephrine treatment. CONCLUSIONS: We found that Mtus1 is specifically spliced in hypertrophic hearts and that the Mtus1A variant has an inhibitory effect on cardiac hypertrophy. Mtus1A is, therefore, a possible diagnostic and therapeutic target for cardiac hypertrophy and failure. PMID- 27385426 TI - Allogeneic Mesenchymal Stromal Cells Overexpressing Mutant Human Hypoxia Inducible Factor 1-alpha (HIF1-alpha) in an Ovine Model of Acute Myocardial Infarction. AB - BACKGROUND: Bone marrow mesenchymal stromal cells (BMMSCs) are cardioprotective in acute myocardial infarction (AMI) because of release of paracrine angiogenic and prosurvival factors. Hypoxia-inducible factor 1-alpha (HIF1-alpha), rapidly degraded during normoxia, is stabilized during ischemia and upregulates various cardioprotective genes. We hypothesized that BMMSCs engineered to overexpress mutant, oxygen-resistant HIF1-alpha would confer greater cardioprotection than nontransfected BMMSCs in sheep with AMI. METHODS AND RESULTS: Allogeneic BMMSCs transfected with a minicircle vector encoding mutant HIF1-alpha (BMMSC-HIF) were injected in the peri-infarct of sheep (n=6) undergoing coronary occlusion. Over 2 months, infarct volume measured by cardiac magnetic resonance (CMR) imaging decreased by 71.7+/-1.3% (P<0.001), and left ventricular (LV) percent ejection fraction (%EF) increased near 2-fold (P<0.001) in the presence of markedly decreased end-systolic volume. Sheep receiving nontransfected BMMSCs (BMMSC; n=6) displayed less infarct size limitation and percent LVEF improvement, whereas in placebo-treated animals (n=6), neither parameters changed over time. HIF1-alpha transfected BMMSCs (BMMSC-HIF) induced angio-/arteriogenesis and decreased apoptosis by HIF1-mediated overexpression of erythropoietin, inducible nitrous oxide synthase, vascular endothelial growth factor, and angiopoietin-1. Cell tracking using paramagnetic iron nanoparticles in 12 additional sheep revealed enhanced long-term retention of BMMSC-HIF. CONCLUSIONS: Intramyocardial delivery of BMMSC-HIF reduced infarct size and improved LV systolic performance compared to BMMSC, attributed to increased neovascularization and cardioprotective effects induced by HIF1-mediated overexpression of paracrine factors and enhanced retention of injected cells. Given the safety of the minicircle vector and the feasibility of BMMSCs for allogeneic application, this treatment may be potentially useful in the clinic. PMID- 27385425 TI - Dietary Nitrate and the Epidemiology of Cardiovascular Disease: Report From a National Heart, Lung, and Blood Institute Workshop. PMID- 27385427 TI - Plasma Fibroblast Growth Factor 23: Clinical Correlates and Association With Cardiovascular Disease and Mortality in the Framingham Heart Study. AB - BACKGROUND: Fibroblast growth factor 23 (FGF23) is emerging as a novel biomarker of bone metabolism, chronic kidney disease, and cardiovascular disease (CVD). However, its clinical correlates and potential predictive role in a community based setting are incompletely understood. METHODS AND RESULTS: We evaluated participants of the Framingham Heart Study (seventh examination cycle of the Offspring cohort plus second examination cycle of the multiethnic Omni cohort) to identify clinical correlates of plasma FGF23 (N=3236) and examine its cross sectional association with vascular function (N=2209), and longitudinal association with 10-year incidence of CVD (N=2823), and all-cause mortality (N=3223).Circulating FGF23 concentrations were positively related to African American and Asian ethnicity, waist circumference, current smoking, serum glucose, history of CVD, and antihypertensive medication use; and negatively related to male sex, hormone replacement therapy, and estimated glomerular filtration rate. Multivariable-adjusted cross-sectional analyses showed no consistent association of FGF23 with vascular function measures. During a median follow-up time of 10.8 years, 347 incident CVD events and 412 deaths occurred. Multivariable-adjusted Cox regression models revealed a positive association of FGF23 with all-cause mortality (hazard ratio [HR] per SD increase, 1.31; 95% CI, 1.20-1.42), but not with incident CVD (HR per SD increase, 1.05; 95% CI, 0.94 1.17). CONCLUSIONS: In our large, community-based sample, FGF23 was associated with mortality risk, but not with vascular function or incident CVD. PMID- 27385428 TI - Systematic Review of Low-Density Lipoprotein Cholesterol Apheresis for the Treatment of Familial Hypercholesterolemia. AB - BACKGROUND: Apheresis is an important treatment for reducing low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia (FH). We systematically reviewed the current literature surrounding LDL-C apheresis for FH. METHODS AND RESULTS: Electronic databases were searched for publications of LDL-C apheresis in patients with FH. Inclusion criteria include articles in English published in 2000-2013 that provide descriptions of practice patterns, efficacy/effectiveness, and costs related to LDL-C apheresis in patients with FH. Data were stratified by country and FH genotype where possible. Thirty-eight studies met the inclusion criteria: 8 open-label clinical trials, 11 observational studies, 17 reviews/guidelines, and 2 health technology assessments. The prevalence of FH was not well characterized by country, and underdiagnosis was a barrier to FH treatment. Treatment guidelines varied by country, with some guidelines recommending LDL-C apheresis as first-line treatment in patients with homozygous FH and after drug therapy failure in patients with heterozygous FH. Additionally, guidelines typically recommended weekly or biweekly LDL-C apheresis treatments conducted at apheresis centers that may last 2 to >3 hours per session. Studies reported a range for mean LDL-C reduction after apheresis: 57-75% for patients with homozygous FH and 58-63% for patients with heterozygous FH. Calculated annual costs (in US$2015) may reach US$66 374 to US$228 956 per patient for weekly treatment. CONCLUSIONS: LDL-C apheresis treatment may be necessary for patients with FH when drug therapy is inadequate in reducing LDL-C to target levels. While apheresis reduces LDL-C, high per-session costs and the frequency of guideline-recommended treatment result in substantial annual costs, which are barriers to the optimal treatment of FH. PMID- 27385429 TI - Acute Kidney Injury Definition and In-Hospital Mortality in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction. AB - BACKGROUND: Acute kidney injury (AKI) has been associated with increased mortality in ST-segment elevation myocardial infarction. We compared the mortality predictive accuracy of the 3 AKI definitions used most widely for patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS AND RESULTS: We included 3771 patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention at 2 Italian hospitals. AKI incidence was evaluated according to creatinine increases of >=25% (AKI-25), >=0.3 mg/dL (AKI 0.3), and >=0.5 mg/dL (AKI-0.5). The primary end point was in-hospital mortality. Overall, 557 (15%), 522 (14%), and 270 (7%) patients developed AKI-25, AKI-0.3, and AKI-0.5, respectively (P<0.01). All AKI definitions independently predicted in-hospital mortality (adjusted odds ratio 4.9 [95% CI 3.1-7.8], 5.4 [95% CI 3.3 8.6], and 8.3 [95% CI 5.1-13.3], respectively; P<0.01 for all). At receiver operating characteristic analysis, the addition of each AKI definition to combined clinical predictors of mortality (age, sex, left ventricular ejection fraction, admission creatinine, creatine kinase-MB peak) found at stepwise analysis significantly improved mortality prognostication (area under the curve increased from 0.89 for clinical predictor combination alone to 0.92 for AKI-25, 0.92 for AKI-0.3, and 0.93 for AKI-0.5; P<0.01 for all). At reclassification analysis, AKI-0.5 added to clinical predictors, provided the highest score in mortality (net reclassification improvement +10% versus AKI-0.3 [P=0.01] and +8% versus AKI-25 [P=0.05]). CONCLUSIONS: Each AKI definition significantly improved the mortality prediction beyond major clinical variables. AKI-0.5 showed a mortality discrimination advantage, suggesting it should be the preferred definition in studies addressing ST-segment elevation myocardial infarction and focusing on short-term mortality. PMID- 27385430 TI - The feasibility of determining the effectiveness and cost-effectiveness of medication organisation devices compared with usual care for older people in a community setting: systematic review, stakeholder focus groups and feasibility randomised controlled trial. AB - BACKGROUND: Medication organisation devices (MODs) provide compartments for a patient's medication to be organised into the days of the week and the recommended times the medication should be taken. AIM: To define the optimal trial design for testing the clinical effectiveness and cost-effectiveness of MODs. DESIGN: The feasibility study comprised a systematic review and focus groups to inform a randomised controlled trial (RCT) design. The resulting features were tested on a small scale, using a 2 * 2 factorial design to compare MODs with usual packaging and to compare weekly with monthly supply. The study design was then evaluated. SETTING: Potential participants were identified by medical practices. PARTICIPANTS: Aged over 75 years, prescribed at least three solid oral dosage form medications, unintentionally non-adherent and self medicating. Participants were excluded if deemed by their health-care team to be unsuitable. INTERVENTIONS: One of three MODs widely used in routine clinical practice supplied either weekly or monthly. OBJECTIVES: To identify the most effective method of participant recruitment, to estimate the prevalence of intentional and unintentional non-adherence in an older population, to provide a point estimate of the effect size of MODs relative to usual care and to determine the feasibility and acceptability of trial participation. METHODS: The systematic review included MOD studies of any design reporting medication adherence, health and social outcomes, resource utilisation or dispensing or administration errors. Focus groups with patients, carers and health-care professionals supplemented the systematic review to inform the RCT design. The resulting design was implemented and then evaluated through questionnaires and group discussions with participants and health-care professionals involved in trial delivery. RESULTS: Studies on MODs are largely of poor quality. The relationship between adherence and health outcomes is unclear. Of the limited studies reporting health outcomes, some reported a positive relationship while some reported increased hospitalisations associated with MODs. The pre-trial focus groups endorsed the planned study design, but suggested a minimum recruitment age of 50-60 years. A total of 35.4% of patients completing the baseline questionnaire were excluded because they already used a MOD. Active recruitment yielded a higher consent rate, but passive recruitment was more cost-effective. The prevalence of intentional non-adherence was 24.7% [n = 71, 95% confidence interval (CI) 19.7% to 29.6%] of participants. Of the remaining 76 participants, 46.1% (95% CI 34.8% to 57.3%) were unintentionally non-adherent. There was no indication of a difference in adherence between the study arms. Participants reported a high level of satisfaction with the design. Five adverse/serious adverse events were identified in the MOD study arms and none was identified in the control arms. There was no discernible difference in health economic outcomes between the four study arms; the mean intervention cost was L20 per month greater for MOD monthly relative to usual supply monthly. CONCLUSIONS: MOD provision to unintentionally non-adherent older people may cause medication-related adverse events. The primary outcome for a definitive MOD trial should be health outcomes. Such a trial should recruit patients by postal invitation and recruit younger patients. FUTURE WORK: A study examining the association between MOD initiation and adverse effects is necessary and a strategy to safely introduce MODs should be explored. A definitive study testing the clinical effectiveness and cost-effectiveness of MODs is also required. STUDY REGISTRATION: Current Controlled Trials ISRCTN 30626972 and UKCRN 12739. FUNDING: This project was funded by National Institute for Health Research (NIHR) Health Technology Assessment Programme and will be published in full in Health Technology Assessment; Vol. 20, No. 50. See the NIHR Journals Library website for further project information. PMID- 27385431 TI - The Rtt107 BRCT scaffold and its partner modification enzymes collaborate to promote replication. AB - Faithful duplication of the entire genome during each cell cycle is key for genome maintenance. Each stage of DNA replication, including initiation, progression, and termination, is tightly regulated. Some of these regulations enable replisomes to overcome tens of thousands of template obstacles that block DNA synthesis. Previous studies have identified a large number of proteins that are dedicated to this mission, including protein modification enzymes and scaffold proteins. Protein modification enzymes can bestow fast and reversible changes on many substrates, and thus are ideal for coordinating multiple events needed to promptly overcome replication impediments. Scaffold proteins can support specific protein-protein interactions that enable protein complex formation, protein recruitment, and partner enzyme functions. Taken together with previous studies, our recent work elucidates that a group of modification and scaffold proteins form several complexes to aid replication progression and are particularly important for synthesizing large replicons. Additionally, our work reveals that the intrinsic plasticity of the replication initiation program can be used to compensate for deficient replication progression. (1). PMID- 27385432 TI - Changes in health-related quality of life with treatment of longer-acting clotting factors: results in the A-LONG and B-LONG clinical studies. AB - INTRODUCTION: In haemophilia, prophylactic infusion of replacement factor can result in improvements in health-related quality of life (HRQoL) when compared with episodic treatment. The Haemophilia-specific Quality of Life (Haem-A-QoL) questionnaire assessed HRQoL in adults with severe haemophilia A or B who received prophylactic or episodic treatment with recombinant factor VIII or IX Fc fusion protein (rFVIIIFc or rFIXFc) in the A-LONG or B-LONG clinical studies. AIMS: Understand changes in HRQoL during the A-LONG and B-LONG trials. METHODS: Group-level and individual-level changes over time for the Haem-A-QoL key domains of 'Physical Health' and 'Sports & Leisure,' and 'Total Score' were evaluated in adults through baseline and 6-month HRQoL assessments. Previously determined responder definitions (RDs) were used for evaluating meaningful subject-level HRQoL improvements. RESULTS: The analysis included 67 A-LONG and 51 B-LONG subjects who completed the Haem-A-QoL (baseline and 6 months). While HRQoL improvements were observed among all treatment groups, greater improvements in HRQoL were observed among subjects who received episodic treatment pre-study (and prophylaxis on-study) compared to those who received hyphenate prophylaxis. Applying the RDs for interpreting 6-month changes, 47.4%/33.3% ('Physical Health'), 35.9%/50.0% ('Sports & Leisure') and 23.9%/33.3% ('Total Score') of A LONG subjects who received individualized or weekly prophylaxis were classified as HRQoL responders. In B-LONG, 69.2%/57.9% ('Physical Health'), 44.4%/56.7% ('Sports & Leisure') and 41.7%/44.1% ('Total Score') of subjects who received individualized or weekly prophylaxis were classified as HRQoL responders. CONCLUSION: Changes in Haem-A-QoL key domains and 'Total Score' suggest that prophylaxis with long-acting rFVIIIFc or rFIXFc resulted in meaningful HRQoL improvements. PMID- 27385433 TI - Gold-catalysed reactions of diynes. AB - In this critical review the reactivity patterns observed with different types of diyne substrates in gold catalysis are discussed. Apart from the many examples from homogeneous catalysis, the few examples from heterogeneous gold catalysis are also included. With a proper arrangement of the two alkynes unique and exciting reactivity patterns like 1,3-carbonyl transpositions, carbene transfer reactions, cascade annulations, macrocyclisations or the formation of gold vinylidene intermediates are observed. These reactions are of interest for organic synthesis, for pharmaceutical and medicinal chemistry and for material science. PMID- 27385434 TI - Using probit regression to disclose the analytical performance of qualitative and semi-quantitative tests. AB - BACKGROUND: The analytical performance of qualitative and semi-quantitative tests is usually studied by calculating the fraction of positive results after replicate testing of a few specimens with known concentrations of the analyte. We propose using probit regression to model the probability of positive results as a function of the analyte concentration, based on testing many specimens once with a qualitative and a quantitative test. METHODS: We collected laboratory data where urine specimens had been analyzed by both a urine albumin ('protein') dipstick test (Combur-Test strips) and a quantitative test (BN ProSpec System). For each dipstick cut-off level probit regression was used to estimate the probability of positive results as a function of urine albumin concentration. We also used probit regression to estimate the standard deviation of the continuous measurement signal that lies behind the binary test response. Finally, we used probit regression to estimate the probability of reading a specific semi quantitative dipstick result as a function of urine albumin concentration. RESULTS: Based on analyses of 3259 specimens, the concentration of urine albumin with a 0.5 (50%) probability of positive result was 57 mg/L at the lowest possible cut-off limit, and 246 and 750 mg/L at the next (higher) levels. The corresponding standard deviations were 29, 83, and 217 mg/L, respectively. Semi quantitatively, the maximum probability of these three readings occurred at a u albumin of 117, 420, and 1200 mg/L, respectively. CONCLUSIONS: Probit regression is a useful tool to study the analytical performance of qualitative and semi quantitative tests. PMID- 27385435 TI - Pleosporalone A, the first azaphilone characterized with aromatic A-ring from a marine-derived Pleosporales sp. fungus. AB - A fungal strain, Pleosporales sp. CF09-1, was isolated from marine sediment collected from the Bohai Sea. A novel azaphilone derivative, named pleosporalone A (1), along with two known analogues, cohaerins A and B (2 and 3), were obtained and identified from the culture extract of Pleosporales sp. CF09-1. Their planar structures were elucidated by detailed analysis of spectroscopic data and by comparison with related known compounds. Pleosporalone A (1) represents the first azaphilone derivative characterised with A-ring aromatisation. Compound 1 showed strong antifungal activity against three plant pathogenic fungi Botrytis cinerea, Rhizopus oryzae and Phytophthora capsici with the MIC values of 0.39, 0.78 and 0.78 MUM, respectively. PMID- 27385437 TI - Limits of Peripheral Blood Mononuclear Cells for Gene Expression-Based Biomarkers in Juvenile Idiopathic Arthritis. AB - Juvenile Idiopathic Arthritis (JIA) is one of the most common chronic disease conditions affecting children in the USA. As with many rheumatic diseases, there is growing interest in using genomic technologies to develop biomarkers for either diagnosis or to guide treatment ("personalized medicine"). Here, we explore the use of gene expression patterns in peripheral blood mononuclear cells (PBMC) as a first step approach to developing such biomarkers. Although PBMC carry many theoretical advantages for translational research, we have found that sample heterogeneity makes RNASeq on PBMC unsuitable as a first-step method for screening biomarker candidates in JIA. RNASeq studies of homogeneous cell populations are more likely to be useful and informative. PMID- 27385439 TI - Fas apoptosis inhibitory molecules: more than death-receptor antagonists in the nervous system. AB - The importance of death receptor (DR) signaling in embryonic development and physiological homeostasis is well established, as is the existence of several molecules that modulate DRs function, among them Fas Apoptotis Inhibitory Molecules. Although FAIM1, FAIM2, and FAIM3 inhibit Fas-induced cell death, they are not structurally related, nor do they share expression patterns. Moreover, they inhibit apoptosis through completely different mechanisms. FAIM1 and FAIM2 protect neurons from DR-induced apoptosis and are involved in neurite outgrowth and neuronal plasticity. FAIM1 inhibits Fas ligand- and tumor necrosis factor alpha-induced apoptosis by direct interaction with Fas receptor and through the stabilization of levels of X-linked inhibitor of apoptosis protein, a potent anti apoptotic protein that inhibits caspases. Low FAIM1 levels are found in Alzheimer's disease, thus sensitizing neurons to tumor necrosis factor alpha and prompting neuronal loss. FAIM2 protects from Fas by direct interaction with Fas receptor, as well as by modulating calcium release at the endoplasmic reticulum through interaction with Bcl-xL. Several studies prove the role of FAIM2 in diseases of the nervous system, such as ischemia, bacterial meningitis, and neuroblastoma. The less characterized member of the FAIM family is FAIM3, which is expressed in tissues of the digestive and urinary tracts, bone marrow and testes, and restricted to the cerebellum in the nervous system. FAIM3 protects against DR-induced apoptosis by inducing the expression of other DR-antagonists such as CFLAR or through the interaction with the DR-adaptor protein Fas associated via death domain. FAIM3 null mouse models reveal this protein as an important mediator of inflammatory autoimmune responses such as those triggered in autoimmune encephalomyelitis. Given the differences between FAIMs and the variety of processes in which they are involved, here we sought to provide a concise review about these molecules and their roles in the physiology and pathology of the nervous system. Even though they share name and inhibit Fas induced cell death, Fas apoptotic inhibitory molecules (FAIMs) are not structurally related and inhibit apoptosis through completely different mechanisms. In this review, we describe FAIM1, FAIM2, and FAIM3 functions in the nervous system, and their implication in diverse pathologies such as neurodegenerative disease, cancer, or autoimmune diseases. PMID- 27385440 TI - Stepwise diagnosis in covert hepatic encephalopathy: critical flicker frequency and MELD-score as a first-step approach. AB - BACKGROUND: The diagnosis of covert hepatic encephalopathy (CHE) by means of portosystemic encephalopathy syndrome (PSE) test is costly and therefore infrequently performed. AIM: To determine the ability of critical flicker frequency (CFF) alone or in combination with laboratory findings, as an initial test to pre-select which patients should undergo further testing for the diagnosis of covert hepatic encephalopathy. METHODS: This single-centre study included all patients with cirrhosis who underwent PSE and CFF in 2011. CHE was defined by abnormal PSE test. Logistic regression analysis was performed to identify predictors of CHE. ROC curves were used to identify cut-offs of these independent predictors. RESULTS: One hundred and seventeen patients were included. Seventy (60%) had CHE with a higher MELD [16 (IQR 13-21); P = 0.001] and lower CFF [38 Hz (IQR 36-41) P = 0.0011]. On multivariate analyses, CFF [OR 0.83 (95% CI 0.74-0.94)] and MELD [OR 1.13 (95% CI 1.04-1.22)] were identified as independent predictors of CHE. Sensitivity and specificity of a CFF cut-off of 43 Hz was 93.5% and 42.9%, and for a MELD cut-off of 24, it was 97.5% and 32.8% respectively. Most patients with a MELD-Score <24 and a CFF >43 Hz did not have CHE (78%) and with a MELD-Score >24 and CFF <43 Hz most patients had CHE (85%). Therefore, 27% of patients could avoid further testing with a diagnostic accuracy of 81%. CONCLUSION: The combination of MELD-score and critical flicker frequency may be used as a first diagnostic step to filter patients, in whom further covert hepatic encephalopathy testing could be avoided. PMID- 27385438 TI - The adipokine lipocalin-2 in the context of the osteoarthritic osteochondral junction. AB - Obesity and osteoarthritis (OA) form a vicious circle in which obesity contributes to cartilage destruction in OA, and OA-associated sedentary behaviour promotes weight gain. Lipocalin-2 (LCN2), a novel adipokine with catabolic activities in OA joints, contributes to the obesity and OA pathologies and is associated with other OA risk factors. LCN2 is highly induced in osteoblasts in the absence of mechanical loading, but its role in osteoblast metabolism is unclear. Therefore, because osteochondral junctions play a major role in OA development, we investigated the expression and role of LCN2 in osteoblasts and chondrocytes in the OA osteochondral junction environment. Our results showed that LCN2 expression in human osteoblasts and chondrocytes decreased throughout osteoblast differentiation and was induced by catabolic and inflammatory factors; however, TGF-beta1 and IGF-1 reversed this induction. LCN2 reduced osteoblast viability in the presence of iron and enhanced the activity of MMP-9 released by osteoblasts. Moreover, pre-stimulated human osteoblasts induced LCN2 expression in human chondrocytes, but the inverse was not observed. Thus, LCN2 is an important catabolic adipokine in osteoblast and chondrocyte metabolism that is regulated by differentiation, inflammation and catabolic and anabolic stimuli, and LCN2 expression in chondrocytes is regulated in a paracrine manner after osteoblast stimulation. PMID- 27385441 TI - Quantifying the effect of tissue deformation on diffusion-weighted MRI: a mathematical model and an efficient simulation framework applied to cardiac diffusion imaging. AB - Cardiac motion presents a major challenge in diffusion weighted MRI, often leading to large signal losses that necessitate repeated measurements. The diffusion process in the myocardium is difficult to investigate because of the unqualified sensitivity of diffusion measurements to cardiac motion. A rigorous mathematical formalism is introduced to quantify the effect of tissue motion in diffusion imaging. The presented mathematical model, based on the Bloch-Torrey equations, takes into account deformations according to the laws of continuum mechanics. Approximating this mathematical model by using finite elements method, numerical simulations can predict the sensitivity of the diffusion signal to cardiac motion. Different diffusion encoding schemes are considered and the diffusion weighted MR signals, computed numerically, are compared to available results in literature. Our numerical model can identify the existence of two time points in the cardiac cycle, at which the diffusion is unaffected by myocardial strain and cardiac motion. Of course, these time points depend on the type of diffusion encoding scheme. Our numerical results also show that the motion sensitivity of the diffusion sequence can be reduced by using either spin echo technique with acceleration motion compensation diffusion gradients or stimulated echo acquisition mode with unipolar and bipolar diffusion gradients. PMID- 27385444 TI - The effect of construal level on unethical behavior. AB - : Construal level theory predicts that people will judge immoral events more harshly when these are presented in a way that elicits a higher construal level, relative to a lower construal level. Previous research supported this prediction using an Israeli sample but not a U.S. SAMPLE: This article compared Israeli and U.S. samples with respect to the interactive effect of utility and construal level on unethical behavioral intentions. We found that construal level did not affect unethical behavioral intentions in either the U.S. samples for low-utility level or the Israeli samples for low- and high-utility levels. In contrast, construal level affected unethical behavioral intentions in the U.S. sample for high-utility level: unethical behavioral intentions were higher in the low construal level compared to the high-construal level. We discuss these findings and suggest additional factors that challenge arguments concerning the direct effect of construal level on unethical behavior. PMID- 27385445 TI - Embedding technology into inter-professional best practices in home safety evaluation. AB - PURPOSE: To explore inter-professional home evaluators' perspectives and needs for building useful and acceptable decision-support tools for the field of home modifications. METHOD: Twenty semi-structured interviews were conducted with a range of home modification professionals from different regions of the United States. The interview transcripts were analyzed with a qualitative, descriptive, perspective approach. RESULTS: Technology supports current best practice and has potential to inform decision making through features that could enhance home evaluation processes, quality, efficiency and inter-professional communication. CONCLUSIONS: Technological advances with app design have created numerous opportunities for the field of home modifications. Integrating technology and inter-professional best practices will improve home safety evaluation and intervention development to meet client-centred and societal needs. Implications for rehabilitation Understanding home evaluators technology needs for home safety evaluations contributes to the development of app-based assessments. Integrating inter-professional perspectives of best practice and technological needs in an app for home assessments improves processes. Novice and expert home evaluators would benefit from decision support systems embedded in app-based assessments. Adoption of app-based assessment would improve efficiency while remaining client centred. PMID- 27385443 TI - How antibodies alter the cell entry pathway of dengue virus particles in macrophages. AB - Antibody-dependent enhancement of dengue virus (DENV) infection plays an important role in the exacerbation of DENV-induced disease. To understand how antibodies influence the fate of DENV particles, we explored the cell entry pathway of DENV in the absence and presence of antibodies in macrophage-like P388D1 cells. Recent studies unraveled that both mature and immature DENV particles contribute to ADE, hence, both particles were studied. We observed that antibody-opsonized DENV enters P388D1 cells through a different pathway than non opsonized DENV. Antibody-mediated DENV entry was dependent on FcgammaRs, pH, Eps15, dynamin, actin, PI3K, Rab5, and Rab7. In the absence of antibodies, DENV cell entry was FcgammaR, PI3K, and Rab5-independent. Live-cell imaging of fluorescently-labeled particles revealed that actin-mediated membrane protrusions facilitate virus uptake. In fact, actin protrusions were found to actively search and capture antibody-bound virus particles distantly located from the cell body, a phenomenon that is not observed in the absence of antibodies. Overall, similar results were seen for antibody-opsonized standard and antibody-bound immature DENV preparations, indicating that the maturation status of the virus does not control the entry pathway. Collectively, our findings suggest that antibodies alter the cell entry pathway of DENV and trigger a novel mechanism of initial virus-cell contact. PMID- 27385447 TI - Isolation of Four New Indole-3-acetic Acid (IAA) Oxidative Metabolites, a Pair of Diasteromers 5-O-beta-D-glucopyranosyl 3,5-Dihydroxy-2-indolinone-3-acetic Acid and 5-O-beta-D-cellobiosyl 3,5-Dihydroxy-2-indolinone-3-acetic Acid from Rice Bran. AB - Four new metabolites related to IAA (indole-3-acetic acid) were isolated from an aqueous methanol extract of rice bran and were elucidated by spectroscopic methods to be a pair of diastereomers of 5-O-beta-D-glucopyranosyl 3,5-dihydroxy 2-indolinone-3-acetic acid (A-1 and A-2) and of 5-O-beta-D-cellobiosyl 3,5 dihydroxy-2-indolinone-3-acetic acid (B-1 and B-2). Compound B-1 was also a diastereomer of compound B-2 at the C3 position with an asymmetric carbon atom on an indolinone skeleton, like the relationship between compounds A-1 and A-2. PMID- 27385446 TI - Resveratrol administration increases Transthyretin protein levels ameliorating AD features- importance of transthyretin tetrameric stability. AB - Previous in vivo work showed that resveratrol has beneficial effects in the AD pathology, resulting in increased expression of transthyretin (TTR). TTR binds Abeta peptide avoiding its aggregation and toxicity, and is reduced in the CSF and plasma, in AD. Further, resveratrol binds TTR, stabilizing the native TTR tetrameric structure. To further explore the mechanism of neuroprotection conferred by TTR in AD, resveratrol was administrated, in the diet, to 5-8 months old AD transgenic female mice carrying just one copy of the mouse TTR gene, for two months. Effects in brain Abeta burden were evaluated by immunohistochemistry, and in total brain Abeta levels by ELISA, showing a striking decrease in both parameters in treated animals. In addition, total brain LRP1 protein levels were increased in treated animals, although its gene expression was unaltered. To further understand the mechanism(s) underlying such improvement in AD features, we measured TTR plasma levels showing that TTR increased in resveratrol-treated mice, whereas liver TTR gene transcription was not altered. These results strengthen the stability hypothesis, which postulates that TTR is unstable in AD leading to accelerated clearance and lower levels. Therefore, resveratrol which stabilizes the TTR tetramer results in TTR normalized clearance, thus increasing the protein plasma levels. In turn, stabilized TTR binds more strongly to Abeta peptide, avoiding its aggregation. Our results represent a step forward to the understanding of the mechanism underlying TTR protection in AD and highlight the possibility of using TTR stabilization as a therapeutic target in AD. PMID- 27385448 TI - Relationship between the Physical Properties and Surface Area of Cellulose Derived from Adsorbates of Various Molecular Sizes. AB - An aqueous suspension of bacterial cellulose (BC) has such physical properties as higher viscosity, emulsion-stabilizing effect and filler retention than cellulose of other origins. The specific surface areas of BC, microfibrillated cellulose and wood pulp were evaluated by determining the maximum amounts of adsorption of Congo red, cellobiose dehydrogenase (CDH) and xyloglucan. There was a positive linear correlation between the above-mentioned physical properties of each cellulose sample and the specific surface area derived from the maximum amount of CDH adsorbed. The highest physical property values for BC result from the largest external surface area of the fibrils of BC to which CDH was adsorbed. PMID- 27385449 TI - Enhancing Effect of beta-Lactoglobulin on the Antioxidative Activity of alpha Tocopherol in an Emulsion of Linoleic Acid. AB - The antioxidative activity of alpha-tocopherol and Trolox, a water-soluble carboxylic acid derivative of alpha-tocopherol, in an emulsion stabilized with the hydrophilic emulsifier, polyoxyethylene (20) sorbitan monolaurate, was evaluated by measuring the changes in linoleic acid content, peroxide value, and thiobarbituric acid value. The activity of alpha-tocopherol and Trolox to depress the autoxidation of linoleic acid was stronger when they were added in the aqueous phase than when added in the oil phase, and Trolox in the aqueous phase was the most effective. The results of interfacial-tension measurements support the idea that the affinity of phenolic antioxidants to the surface layer of oil droplets might be related to their antioxidative activity. The antioxidative activity of alpha-tocopherol and Trolox added in the oil phase was markedly enhanced by using beta-lactoglobulin together with Tween 20 to stabilize a linoleic acid emulsion. The results of a linoleic acid determination with cold and radioactive linoleic acid indicate that linoleic acid in a complex with the beta-lactoglobulin molecule would be effectively protected by the phenolic antioxidants, alpha-tocopherol and Trolox, against autoxidation. PMID- 27385450 TI - Characterization of Molecular Structure of Starch Granules in Suspension-cultured Cells from Ipomoea cordatotriloba Denn. AB - The molecular structure of starch granules formed in suspension-cultured cells of Ipomoea cordatotriloba Denn. was characterized by its chain length distribution, which was compared to those of the starches from the root and leaf of the original plant. The cultured cell starches were spherical and had a very small granule size (about 2 MUm). The debranched starches roughly separated into three fractions during gel-permeation chromatography, and the fractions were defined as Fr.1, 2, and 3, respectively. The chain length distribution of the debranched cultured cell starch showed that the high molecular weight fraction (Fr.1), referred to as an amylose fraction, was much less than those of the root and leaf starches. The ratio of the two lower fractions (Fr.3/Fr.2) of the cultured cell starch, which was mainly derived from unit chains of amylopectin, was greatest among the starches, suggesting that the amylopectin from the cultured cell starch has much shorter unit chains. By X-ray diffraction analysis, it was found that both cultured cell and leaf starch granules have low crystallinity. PMID- 27385451 TI - NADPH Oxidase System as a Superoxide-generating Cyanide-Resistant Pathway in the Respiratory Chain of Corynebacterium glutamicum. AB - The respiratory chain of Corynebacterium glutamicum was investigated, especially with respect to a cyanide-resistant respiratory chain bypass oxidase. The membranes of C. glutamicum had NADH, succinate, lactate, and NADPH oxidase activities, and menaquinone, and cytochromes a 598, b 562(558), and c 550 as respiratory components. The NADH, succinate, lactate, and NADPH oxidase systems, all of which were more cyanide-resistant than N,N,N',N'-tetramethyl-p-phenylene diamine oxidase activity (cytochrome aa 3 terminal oxidase), had different sensitivities to cyanide; the cyanide sensitivity of these oxidase systems increased in the order, NADPH, lactate, NADH, and succinate. Taken together with the analysis of redox kinetics in the cytochromes and the effects of respiratory inhibitors, the results suggested that there is a cyanide-resistant bypass oxidase branching at the menaquinone site, besides cyanide-sensitive cytochrome oxidase in the respiratory chain. H(+)/O measurements with resting cells suggested that the cyanide-sensitive respiratory chain has two or three coupling sites, of which one is in NADH dehydrogenase and the others between menaquinone and cytochrome oxidase, but the cyanide-resistant bypass oxidase may not have any proton coupling site. NADPH and lactate oxidase systems were more resistant to UV irradiation than other systems and the UV insensitivity was highest in the NADPH oxidase system, suggesting that a specific quinone resistant to UV or no such a quinone works in at least NADPH oxidase system while the UV-sensitive menaquinone pool does in other oxidase systems. Furthermore, superoxide was generated in well washed membranes, most strongly in the NADPH oxidase system. Thus, it was suggested that the cyanide-resistant bypass oxidase system of C. glutamicum is related to the NADPH oxidase system, which may be involved in generation of superoxide anions and probably functions together with superoxide dismutase and catalase. PMID- 27385452 TI - Solanapyrones, Phytotoxins Produced by Alternaria solani: Biosynthesis and Isolation of Minor Components. AB - Two minor components of solanapyrones D and E, phytotoxins from Alternaria solani, were isolated. The absolute stereochemistry of D and the optical purity of solanapyrones A and D were determined by chemical transformation and measurement of the CD spectrum. In addition, complete signal assignment of the (1)H- and (13)C-NMR spectra of solanapyrones A and D, and their solution conformations were studied. Feeding experiments with various isotopically labeled acetates and methionine established the biosynthetic pathway of solanapyrones. The phytotoxicity of solanapyrones on lettuce seedlings is discussed. PMID- 27385453 TI - Inhibition of Photosystem II of Spinach by Lichen-derived Depsides. AB - Barbatic acid, a lichen-derived depside, inhibited oxygen evolution in spinach thylakoid membranes. It also affected parameters of Chl fluorescence, (Fm'-F)/F and Fv/Fm. Using specific donors and acceptors of electrons, we found two sites of inhibition in the PS II complex. The primary site, which is responsible for the inhibition of oxygen evolution, is at the reducing side of QA, possibly at QB. The other site is at the oxidizing side of P680 but not in the oxygen evolving complex, suggesting Yz as the target. At both sites, irreversible binding of the depside to the targets seems to be responsible for the inhibitions. Among the 8 lichen acids compared, barbatic acid was the most potent inhibitor for both the reducing site and oxidizing site. PMID- 27385454 TI - New Aldobiuronic Acid, 3-O-alpha-D-Glucopyranuronosyl-L-rhamnopyranose, from an Acidic Polysaccharide of Chlorella vulgaris. AB - The new aldobiuronic acid, 3-O-alpha-D-glucopyranuronosyl-L-rhamnopyranose, was isolated from the acid hydrolyzate of an acidic polysaccharide in cells of Chlorella vulgaris K-22. Its structure was elucidated by NMR spectroscopic analyses. PMID- 27385455 TI - Morphological Changes in Insect BM-N4 Cells Induced by Nocardamine. AB - Nocardamine, a kind of siderophore, was isolated as an inducer of morphological changes in the insect cells, BM-N4. It changed the morphology of the cells from round to an unusual spindle shape. This activity of nocardamine was inhibited by adding the ferric ion. PMID- 27385456 TI - Isolation of An Aroma Precursor of Benzaldehyde from Tea Leaves (Camellia sinensis var. sinensis cv. Yabukita). AB - The cyanoglycoside, prunasin, was isolated for the first time as an aroma precursor of benzaldehyde from fresh tea leaves (Camellia sinensis var. sinensis cv. Yabukita). Prunasin was readily hydrolyzed by a crude enzyme prepared from the fresh tea leaves to liberate benzaldehyde. The isomerization of prunasin under neutral conditions was also recognized. PMID- 27385457 TI - Prevention of Copper-mediated Lipoprotein Oxidation by Heme-containing Proteins from the Plasma of Japanese Eel Anguilla japonica. AB - A brown-colored fraction containing heme was separated from the lipoprotein-free plasma of Japanese eel (Anguilla japonica). This fraction prevented the oxidation of very-low-density lipoprotein incubated with CuSO4 ranging in concentration from 0.5 to 3 MUM. The antioxidant activity seemed to derive from the heme binding proteins of the brown-colored fraction. PMID- 27385458 TI - Syntheses of Sphingomyelins and Ceramides Bearing a Docosahexaenoyl or Arachidonoyl Group. AB - Sphingomyelins and ceramides bearing a docosahexaenoyl or arachidonoyl group were synthesized from sphingosylphosphorylcholine and sphingosine, respectively, by dicyclohexylcarbodiimide-mediated acylation. PMID- 27385459 TI - Isolation and Some Properties of the Antimicrobial Peptide (Pa-AMP) from the Seeds of Pokeweed (Phytolacca americana). AB - An antimicrobial peptide, designated Pa-AMP, was purified by gel filtration on Sephadex G-75 followed by S-Sepharose, Cosmosil-SP, and reverse-phase HPLC from the seeds of pokeweed (Phytolacca americana). Pa-AMP is a basic peptide having an isoelectric point of over 10 and its extinction coefficient at 280 nm of 1% aqueous solution was 7.7. Pa-AMP has a molecular mass of 4 kDa and 3.4 kDa on tricine SDS-PAGE under nonreducing and reducing conditions, respectively. The N terminal amino acid of Pa-AMP was blocked. The concentrations of peptide required for 50% inhibition (IC50) of the growth of plant pathogenic fungi, Gram-positive, and Gram-negative bacteria were 3 to 41 MUg/ml. Differing from other peptides, Pa AMP inhibited the growth of some Gram-negative bacteria. PMID- 27385460 TI - High consumption of tetracyclines for acne treatment among young Danish adults. AB - BACKGROUND: Tetracyclines are used as acne treatment in adolescents worldwide. A large increase in the consumption of antimicrobial agents in Danish primary health care was recently linked to high levels of tetracycline use in adolescents. METHODS: Here we closely examine how demographic factors influenced tetracycline use from 2005 to 2014 using consumption data from primary health care expressed as defined daily doses (DDDs) per 1000 inhabitants per day (DID) and number of persons treated per 1000 inhabitants. RESULTS: From 2005 to 2013, tetracycline consumption increased by 54% followed by a decrease of 14% in 2014. Increases were especially pronounced in persons aged 15-39 years where nearly 9000 additional persons were treated with tetracyclines. CONCLUSIONS: This study shows a long-lasting high consumption of tetracyclines in young Danes with a notable recent decrease breaking the otherwise worrying trend. To obtain a further decrease, focus on public awareness and suitable acne treatment guidelines are highly important. PMID- 27385461 TI - Postponing parenthood to advanced age. AB - The aim of the Postponing Parenthood project was to investigate several aspects of the delaying of childbearing phenomenon in Sweden and Norway, such as medical risks and parental experiences. Data were retrieved from the Swedish and Norwegian Medical Birth Registers and three different cohorts: the Swedish Young Adult Panel Study, the Norwegian Mother and Child Cohort, and the Swedish Women's Experiences of Childbirth cohort. Postponing childbirth to age 35 years and later increased the risk of rare but serious pregnancy outcomes, such as stillbirth and very preterm birth. Older first-time parents were slightly more anxious during pregnancy, and childbirth overall was experienced as more difficult, compared with younger age groups. First-time mothers' satisfaction with life decreased from about age 28 years, both when measured during pregnancy and early parenthood. Delaying parenthood to mid-30 or later was more related to lifestyle than socioeconomic factors, suggesting that much could be done in terms of informing young persons about the limitations of fertility and assisted reproductive techniques, and the risks associated with advanced parental age. PMID- 27385462 TI - Unconventional Electronic Structure and Chlorination/Dechlorination Mechanisms of (#1911)C64 Fullerene. AB - We report a computational work on the electronic structure and derivatization of (#1911)C64. By means of computations based on density functional theory, we find that (#1911)C64 in states of closed-shell singlet (CS), open-shell singlet (OS), and triplet are iso-energetic with an energy difference less than 0.1 kcal mol( 1). The regioselective chlorine additions on CS, OS, and triplet C64 are studied, and the formation of experimentally observed C64Cl4 and C64Cl8 have been successfully elucidated for the first time. In addition, the dechlorination processes of formed chlorofullerenes are also explored. In contrast to the radical Cl addition, the reverse reaction is a themolysis process, and the decomposition sequence is proved to be simply determined by the C-Cl bond length. PMID- 27385463 TI - Plasmapheresis, intravenous immunoglobulins and bethametasone - a combined protocol to treat autoimmune congenital heart block: a prospective cohort study. AB - OBJECTIVES: At the moment there are no standard guidelines for the treatment of autoimmune congenital heart block (CHB). We set out to carry out a prospective cohort study to evaluate the benefits, limits, and safety of a combined therapy protocol to treat antibody-related CHB. METHODS: Twelve consecutive pregnant patients positive to anti-SSA/Ro +/- anti-SSB/La antibodies in whom CHB was detected were prospectively evaluated from 2009 to 2014. The treatment protocol consisted of: weekly plasmapheresis, fortnightly intravenous immunoglobulins (IVIG), and daily 4 mg betamethasone from CHB detection until delivery; IVIG was administered to the neonates soon after birth. RESULTS: At the time CHB was detected, six of the foetuses presented atrioventricular blocks of 2(nd) degree type and six of 3(rd) degree type. Two of the foetuses with a 2(nd) degree block reverted to a 1st degree block and one to a normal atrioventricular conduction. The condition was stable throughout the pregnancy in the other three cases of 2(nd) degree block. All six 3(rd) degree blocks were stable during pregnancy and confirmed at birth. After a mean of 37.6 months +/- 19.6 SD post-birth, the infants with 1st, normal sinus rhythm, and 2(nd) degree blocks at birth were all found to be stable. During the follow-up (29 months +/- 19.8 SD), pacemakers were implanted in three of the six infants with 3(rd) degree blocks. CONCLUSIONS: This combined therapy seems to be effective and safe in treating 2(nd) degree CHB, while its efficacy in treating 3rd degree CHB remains to be established. PMID- 27385465 TI - Monitoring of kidney function in older people living with HIV. PMID- 27385464 TI - Biospectroscopy of Nanodiamond-Induced Alterations in Conformation of Intra- and Extracellular Proteins: A Nanoscale IR Study. AB - The toxicity of nanomaterials raises major concerns because of the impact that nanomaterials may have on health, which remains poorly understood. We need to explore the fate of individual nanoparticles in cells at nano and molecular levels to establish their safety. Conformational changes in secondary protein structures are one of the main indicators of impaired biological function, and hence, the ability to identify these changes at a nanoscale level offers unique insights into the nanotoxicity of materials. Here, we used nanoscale infrared spectroscopy and demonstrated for the first time that nanodiamond-induced alterations in both extra- and intracellular secondary protein structures lead to the formation of antiparallel beta-sheet, beta-turns, intermolecular beta-sheet, and aggregation of proteins. These conformational changes of the protein structure may result in the loss of functionality of proteins and in turn lead to adverse effects. PMID- 27385466 TI - Robust Maleimide-Functionalized Gold Surfaces and Nanoparticles Generated Using Custom-Designed Bidentate Adsorbates. AB - A series of custom-designed alkanethioacetate ligands were synthesized to provide a facile method of attaching maleimide-terminated adsorbates to gold nanostructures via thiolate bonds. Monolayers on flat gold substrates derived from both mono- and dithioacetates, with and without oligo(ethylene glycol) (OEG) moieties in their alkyl spacers, were characterized using X-ray photoelectron spectroscopy, polarization modulation infrared reflection-absorption spectroscopy, ellipsometry, and contact angle goniometry. For all adsorbates, the resulting monolayers revealed that a higher packing density and more homogeneous surface were generated when the film was formed in EtOH, but a higher percentage of bound thiolate was obtained in THF. A series of gold nanoparticles (AuNPs) capped with each adsorbate were prepared to explore how adsorbate structure influences aqueous colloidal stability under extreme conditions, as examined visually and spectroscopically. The AuNPs coated with adsorbates that include OEG moieties exhibited enhanced stability under high salt concentration, and AuNPs capped with dithioacetate adsorbates exhibited improved stability against ligand exchange in competition with dithiothreitol (DTT). Overall, the best results were obtained with a chelating dithioacetate adsorbate that included OEG moieties in its alkyl spacer, imparting improved stability via enhanced solubility in water and superior adsorbate attachment owing to the chelate effect. PMID- 27385467 TI - Early Feeding Practices and Weight Status at One Year of Age: A Comparison of Hispanic Immigrant Mother-Infant Dyads with Participants of the Infant Feeding Practices Study II. AB - BACKGROUND: Hispanic preschoolers have higher rates of BMI >=85th percentile than any other racial/ethnic group. To identify underpinnings of this disparity, we compared early feeding practices and subsequent weight status for a sample of infants of low-income, Hispanic immigrant mothers with participants from the Infant Feeding Practices Study II (IFPS II). METHODS: Proyecto de Bebes Hispanos Saludables (PBHS) collected medical record data for mother-infant dyads (n = 550) from a large pediatric clinic for low-income families and merged it with IFPS II data (n = 1502) to compare early feeding practices and late infancy weight status. RESULTS: Mode of milk delivery for PBHS mothers was less likely to be exclusive breastfeeding at 6 months (9.0% vs. 27.5%), but more likely to be both breast and bottle feeding (43.5% vs. 26.3%) compared to IFPS II mothers. No difference was found in age for solid food introduction. Weight for age of PBHS infants was more likely to be >=85th percentile at 12 months than IFPS II infants (39.1% vs. 25.4%). Both PBHS and IFPS II infants were more likely to be >=85th percentile at 1 year if mode of milk delivery was bottle only at 6 months compared to those who were breastfed only, even after adjusting for potential confounders. CONCLUSION: Differences in PBHS and IFPS II feeding practices and weight status suggest additional studies of modifiable, early life risk factors are needed to inform clinical and public health interventions that reduce childhood obesity for this growing sector of the US population. PMID- 27385469 TI - First report of monomicrobial Candida parapsilosis necrotizing fasciitis. AB - Candida parapsilosis is an emerging pathogen worldwide. It commonly causes soft tissue infection; however, to our knowledge there has been no previous report of monomicrobial necrotizing soft tissue infection (NSTI) secondary to C. parapsilosis. We report the first case of NSTI caused by C. parapsilosis in an immunocompromised renal transplant patient, with the diagnosis proven both histologically and microbiologically. Our patient required aggressive surgical intervention and antifungal therapy, with postoperative survival at 90 days. PMID- 27385468 TI - FOXM1 regulates proliferation, senescence and oxidative stress in keratinocytes and cancer cells. AB - Several transcription factors, including the master regulator of the epidermis, p63, are involved in controlling human keratinocyte proliferation and differentiation. Here, we report that in normal keratinocytes, the expression of FOXM1, a member of the Forkhead superfamily of transcription factors, is controlled by p63. We observe that, together with p63, FOXM1 strongly contributes to the maintenance of high proliferative potential in keratinocytes, whereas its expression decreases during differentiation, as well as during replicative induced senescence. Depletion of FOXM1 is sufficient to induce keratinocyte senescence, paralleled by an increased ROS production and an inhibition of ROS scavenger genes (SOD2, CAT, GPX2, PRDX). Interestingly, FOXM1 expression is strongly reduced in keratinocytes isolated from old human subjects compared with young subjects. FOXM1 depletion sensitizes both normal keratinocytes and squamous carcinoma cells to apoptosis and ROS-induced apoptosis. Together, these data identify FOXM1 as a key regulator of ROS in normal dividing epithelial cells and suggest that squamous carcinoma cells may also use FOXM1 to control oxidative stress to escape premature senescence and apoptosis. PMID- 27385470 TI - Understanding individual differences in representational abstraction: The role of working memory capacity. AB - Several studies have reported differences in categorization strategies among participants: some learn a category by making abstraction across the category members while others use a memorization strategy. Despite the prevalence of these differences, little attention has been paid to investigating what influences some to use an abstraction strategy and others a memorization strategy. The current study had two goals: in a first experiment we investigated whether these differences were stable across time, using the parallel form method often used in psychometric research, and in a second experiment we investigated whether the individual differences in categorization strategy were related to working memory capacity. We used a modelling strategy, in which we not only focused on full abstraction and memorization strategies, but also on intermediate strategies in which some category members are abstracted and others are not. The first study revealed that the individual abstraction strategy of individual participants in two different experiments, performed at different times, correlate significantly, and second study showed that these individual differences were related to the working memory capacity of the participants. PMID- 27385471 TI - Sex-linked differences in the course of chronic kidney disease and congestive heart failure: a study in 5/6 nephrectomized Ren-2 transgenic hypertensive rats with volume overload induced using aorto-caval fistula. AB - The role of hypertension and the renin-angiotensin system (RAS) in sex-related differences in the course of chronic kidney disease (CKD) and congestive heart failure (CHF) remain unclear, especially when the two diseases are combined. In male and female Ren-2 transgenic rats (TGR), a model of hypertension with activation of endogenous RAS, CKD was induced by 5/6 renal mass reduction (5/6 NX) and CHF was elicited by volume overload achieved by creation of an aorto caval fistula (ACF). The primary aim of the study was to examine long-term CKD- and CHF-related mortality, especially in animals with CKD and CHF combined, with particular interest in the potential sex-related differences. The follow-up period was 23 weeks after the first intervention (5/6 NX). We found, first, that TGR did not exhibit sexual dimorphism in the course of 5/6 NX-induced CKD. Second, in contrast, TGR exhibited important sex-related differences in the course of ACF-induced CHF-related mortality: intact female TGR showed higher survival rate than male TGR. This situation is reversed in the course of combined 5/6 NX-induced CKD and ACF-induced CHF-related mortality: intact female TGR exhibited poorer survival than male TGR. Third, the survival rate in animals with combined 5/6 NX-induced CKD and ACF-induced CHF was significantly worsened as compared with rat groups that were exposed to 'single organ disease'. Collectively, our present results clearly show that CKD aggravates long-term mortality of animals with CHF. In addition, TGR exhibit remarkable sexual dimorphism with respect to CKD- and CHF-related mortality, especially in animals with combined CKD and CHF. PMID- 27385473 TI - Adherence to a Low-Support Cognitive Remediation Training Program for Psychosis. AB - Cognitive remediation (CR) has emerged as the treatment of choice for impaired cognition in psychosis. However, little is known about adherence rates and factors predicting adherence to CR, particularly in clinical settings where high level therapist support is unavailable. This study aimed to establish adherence rates and examine variables predicting adherence to a computerized CR program for psychosis (with minimal support). Patients with psychosis (n = 61) participated in an 8-week CR program. Results showed 46% completed a meaningful amount of CR training. The fully adherent (>80% of the prescribed amount) and nonadherent groups differed where adherent participants had poorer working-memory and higher negative symptom scores. These findings suggest that approximately half of the sample were adherent to treatment despite minimal therapist support. Furthermore, higher cognitive deficits and negative symptoms did not impede adherence, and may have contributed to patients' motivation to complete the program. PMID- 27385472 TI - Risk and Protective Factors, Perceptions of Family Environment, Ethnicity, and Schizophrenia Symptoms. AB - The family environment can play either a detrimental or a protective role in symptom severity for people with schizophrenia. The current study examined both patient and caregiver perspectives of the family environment in an ethnically diverse sample of 221 patients with schizophrenia. We hypothesized that environments characterized by high levels of perceived caregiver criticism, low perceived caregiver warmth, and low family cohesion (from both the patient and caregiver perspective) would predict greater symptom severity. As expected, results demonstrated that lower patient ratings of family cohesion and caregiver warmth were associated with greater symptom severity. However, once put into a hierarchical regression analysis, only patient ratings of family cohesion remained significant. Ethnic patterns were also examined and revealed that family cohesion may be particularly protective for ethnic minorities. Study implications are discussed. PMID- 27385474 TI - Work out by Walking: A Pilot Exercise Program for Individuals With Schizophrenia Spectrum Disorders. AB - The health benefits of exercise are well documented, yet annual health care costs related to physical inactivity are well within the billions. Furthermore, individuals with schizophrenia spectrum disorders (SSDs) are more likely to lead sedentary lives, exercise less than the general population, and die prematurely from preventable causes. Previous research examining the effects of exercise on individuals with SSDs has been encouraging yet limited in creating accessible and sustainable interventions. The current pilot study developed and evaluated the impact of Work out by Walking (WOW), a multicomponent group walking intervention on the health of 16 individuals with SSDs. Results indicated improvements in indicators of physical health, activity level, social support, and mental health and a high level of program satisfaction. Future research should examine multicomponent group walking programs for individuals with SSDs in larger samples and with the inclusion of a comparison condition. PMID- 27385475 TI - Negative Consequences of Family Caregiving for Veterans With PTSD and Dementia. AB - Recent research shows veterans with posttraumatic stress disorder (PTSD) are twice as likely as other veterans to develop dementia. However, no studies to date have examined the impact of co-existing PTSD and dementia on family caregivers, who provide the majority of care to these veterans. Using the Stress Process Model, the current investigation explored the similarities and differences in psychosocial, health, and service use outcomes among caregivers assisting veterans with PTSD and dementia compared with caregivers assisting veterans with dementia only. Caregivers of veterans with PTSD and dementia indicated that their relative exhibited more difficult behavior symptoms and used more community services. These caregivers also reported more difficulties understanding veterans' memory problems and more physical strain. Together, results suggested caregivers of veterans with both PTSD and dementia were at greater risk of negative caregiving consequences. Implications and suggestions for future research are discussed. PMID- 27385476 TI - A sequence-specific polymerase chain reaction method for HNA-2 genotyping: homozygous c.843A>T mutation predicts the absence of CD177. AB - BACKGROUND: Human neutrophil antigen-2 is located on a glycosylphosphatidylinositol-anchored receptor, CD177. Humans not expressing CD177 on their neutrophils may, under defined conditions, form isoantibodies. The genetic background for the absence of CD177 is not fully understood, and genetic screening of patients and donors is currently unavailable. A recent study has documented two mutations associated with CD177 absence: a nonsense polymorphism c.843A>T and a single-base deletion c.1011delG. STUDY DESIGN AND METHODS: First, we aimed to demonstrate that these newly described mutations are indeed associated with the absence of CD177. DNA fragments from isoimmunized, CD177 negative individuals were sequenced (n = 5). An additional five negative and 10 positive individuals were also analyzed. Second, we aimed to establish a sequence specific primer (SSP) polymerase chain reaction method for easy and rapid detection of these mutations. RESULTS: None of 10 CD177-positive individuals, but four of 10 CD177-negative individuals were homozygous for the A>T mutation at Position c.843, including three of five isoimmunized individuals. This finding is supportive for the reported association. Surprisingly, and in contrast to the initial report, c.1011delG was not detected in our cohort. Furthermore, a two step SSP method for c.843A>G was successfully established. CONCLUSION: c.843A>T, but not c.1011delG, is associated with the absence of CD177 in a significant number of individuals, including CD177-isoimmunized women. The c.843A>T mutation is easily detectable by a newly established SSP, but screening for this mutation will only provide sufficient evidence for a final diagnosis in case of homozygosity for the c.843T allele. PMID- 27385477 TI - Endocytosis Mechanism of Nano Metal-Organic Frameworks for Drug Delivery. AB - The pathway of internalization and final fate of a specific metal-organic framework (MOF) in cells has been investigated for the first time. This study is based on two calcein-loaded UiO-66 samples with particle sizes of 150 and 260 nm (i.e., cal@150 UiO-66 and cal@260 UiO-66, respectively), and shows that the active trafficking of cal@150 UiO-66 is done almost exclusively through clathrin mediated endocytosis, whereas the uptake of cal@260 UiO-66 is a combination of both clathrin and caveolae-mediated endocytosis. Colocalization studies with a lysosomal marker showed that cal@150 UiO-66 is located mostly in lysosomes for further degradation, whereas cal@260 UiO-66 seems to avoid the lysosomal degradation and potentially deliver the cargo molecules in the cytosol, allowing their distribution to different cellular organelles. This study reveals the importance of the internalization processes of MOFs, particularly the relevance of their particle size, and also the critical significance of their final fate to become an efficient drug delivery system. Based on these results, it is possible that extremely small particle-sized MOFs are not the most efficient carriers and instead relatively medium-sized particles are required. PMID- 27385478 TI - Quality of life in patients with allergic rhinitis: a clinical trial comparing the use of bilastine versus loratadine. AB - OBJECTIVES: The aim of this study was to determine whether there were differences in health-related quality of life of patients with allergic rhinitis treated with bilastine 20 mg compared to those treated with loratadine 10 mg. DESIGN: This was a prospective randomised double-blinded study. SETTING: Otolaryngology outpatient clinics in Criciuma, state of Santa Catarina, Brazil. PARTICIPANTS: Seventy-three patients, aged between 18 and 63 years, of whom 36 were treated with loratadine 10 mg and 37 with bilastine 20 mg with medication administered once a day for 10 days. MAIN OUTCOME MEASURES: The outcome was quality of life as assessed by the modified Rhinoconjunctivitis Quality of Life Questionnaire (RQLQm), which was applied at baseline and after 10 days of treatment. RESULTS: The use of bilastine 20 mg or loratadine 10 mg significantly reduced RQLQm scores after 10 days of treatment (P < 0.001); however, there was no statistically significant difference between the two treatment groups (P > 0.05). CONCLUSIONS: Health-related quality of life in patients with allergic rhinitis improved significantly after 10 days of treatment with loratadine and bilastine, and the effectiveness of both was equivalent. PMID- 27385479 TI - Long-term impact of stroke on patients' health-related quality of life. AB - PURPOSE: This international study aims to examine the size and determinants of the impact of stroke on five-year survivors' health-related quality of life (HRQoL) in four different European countries. METHOD: Patients were recruited consecutively in four European rehabilitation centers. Five years after stroke, the EuroQol-visual analog scale (EQ-VAS) was administered in 226 first-ever stroke patients. Impact of stroke was determined by calculating EQ-VAS z-norm scores (= deviation - expressed in SD - of patients' EQ-VAS level relative to their age-and gender-matched national population norms). Determinants of EQ-VAS z norm scores were identified using multivariate linear regression analysis. RESULTS: Five years post-stroke, patients' mean EQ-VAS was 63.74 (SD = 19.33). Mean EQ-VAS z-norm score was -0.57 [95%CI: (-0.70)-(-0.42)]. Forty percent of the patients had an EQ-VAS z-norm score <-0.75 SD; 52% had an EQ-VAS z-norm score between -0.75 and +0.75 SD, only 8% scored >+0.75 SD. Higher patients' levels of depression, anxiety and disability were associated with increasingly negative EQ VAS z-norm scores (adjusted R2 = 0.392). CONCLUSIONS: Five years after stroke, mean HRQoL of stroke survivors showed large variability and was more than 1/2 SD below population norm. Forty percent had a HRQoL level below, 52% on, and 8% above population norm. The variability could only partially be explained by the variables considered in this study. Longitudinal studies are needed to increase our understanding of the size and determinants of the impact of stroke on the HRQoL of long-term stroke survivors. Implications for rehabilitation The current European concept of stroke rehabilitation is focused on the acute and sub-acute rehabilitation phase, i.e., in the first months after stroke. The results of this study show that at five years after stroke, the mean level of HRQoL of stroke survivors remains below the healthy population level. This finding shows the need for continuation of rehabilitation in the chronic phase. At five years after stroke, higher patients' levels of depression, anxiety and disability were associated with lower scores for HRQoL. This finding implicates that chronic rehabilitation programs should be multi-faceted in order to increase long-term survivors' psychosocial outcomes. PMID- 27385480 TI - Thermal and magnetic anomalies of alpha-iron: an exploration by extended x-ray absorption fine structure spectroscopy and synchrotron x-ray diffraction. AB - The local structure and dynamics of alpha-iron have been investigated by extended x-ray absorption fine structure (EXAFS) spectroscopy and x-ray diffraction (XRD) in order to shed light on some thermal and magnetic anomalies observed in the last decades. The quantitative EXAFS analysis of the first two coordination shells reveals a peculiar local vibrational dynamics of alpha-iron: the second neighbor distance exhibits anharmonicity and vibrational anisotropy larger than the first neighbor distance. We search for possible distortions of the bcc structure to justify the unexplained magnetostriction anomalies of alpha-iron and provide a value for the maximum dislocation of the central Fe atom. No thermal anomalies have been detected from the current XRD data. On the contrary, an intriguing thermal anomaly at about 150 K, ascribed to a stiffening of the Fe-Fe bonds, was found by EXAFS. PMID- 27385481 TI - Angiographic underestimation of disease severity in the left anterior descending artery: a fractional flow reserve analysis. AB - OBJECTIVES: This study compared the prevalence of angiographic underestimation of left anterior descending artery (LAD) lesions with non-LAD lesions. BACKGROUND: Coronary angiography cannot assess the functional severity of a coronary stenosis. Previous studies suggested that lesions of the LAD are more often angiographically underestimated, but evidence is limited. MATERIALS AND METHODS: Fractional flow reserve (FFR) was performed in 335 coronary lesions (187 LAD lesions and 148 non-LAD lesions). A visually estimated diameter stenosis of at least 70% was considered functionally significant. An FFR value of up to 0.80 was considered significant. Multivariable analyses were carried out. RESULTS: Angiographically, LAD lesions as well as non-LAD lesions were considered functionally significant in 29% (P=0.94). FFR showed significant stenosis of the LAD in 52% compared with 24% in non-LAD lesions (P<0.001). Underestimation was observed in 30% of LAD lesions compared with 11% in non-LAD lesions (P<0.001). The adjusted odds ratio for underestimation in LAD lesions in comparison with non LAD lesions was 3.48 (95% confidence interval 1.89-6.41; P<0.001). CONCLUSION: Underestimation of the functional severity of a coronary stenosis is more common in LAD lesions. FFR should be performed more often for intermediate stenosis of the LAD. PMID- 27385482 TI - Molecular clock integration of brown adipose tissue formation and function. AB - The circadian clock is an essential time-keeping mechanism that entrains internal physiology to environmental cues. Despite the well-established link between the molecular clock and metabolic homeostasis, an intimate interplay between the clock machinery and the metabolically active brown adipose tissue (BAT) is only emerging. Recently, we came to appreciate that the formation and metabolic functions of BAT, a key organ for body temperature maintenance, are under an orchestrated circadian clock regulation. Two complementary studies from our group uncover that the cell-intrinsic clock machinery exerts concerted control of brown adipogenesis with consequent impacts on adaptive thermogenesis, which adds a previously unappreciated temporal dimension to the regulatory mechanisms governing BAT development and function. The essential clock transcriptional activator, Bmal1, suppresses adipocyte lineage commitment and differentiation, whereas the clock repressor, Rev-erbalpha, promotes these processes. This newly discovered temporal mechanism in fine-tuning BAT thermogenic capacity may enable energy utilization and body temperature regulation in accordance with external timing signals during development and functional recruitment. Given the important role of BAT in whole-body metabolic homeostasis, pharmacological interventions targeting the BAT-modulatory activities of the clock circuit may offer new avenues for the prevention and treatment of metabolic disorders, particularly those associated with circadian dysregulation. PMID- 27385483 TI - Risk Factors for Conversion of Laparoscopic Cholecystectomy to Open Surgery: A New Predictive Statistical Model. AB - INTRODUCTION: Although laparoscopic cholecystectomy is currently the standard treatment for benign gallbladder pathologies, some cases still require conversion to open cholecystectomy. Since open cholecystectomy has a significantly higher morbidity rate and a lengthier stay in the hospital compared with laparoscopic surgery, predicting this conversion would grant a great advantage in the management of cholecystitis. Therefore, in this study, we aimed to develop a predictive statistical model. MATERIALS AND METHODS: Between August 2006 and January 2011, 1335 laparoscopic cholecystectomies were initiated at the General Surgery Department of Hacettepe University. One hundred four of these cases were started as laparoscopic surgeries, but converted to open cholecystectomies. In our study, we randomly chose 104 laparoscopically completed cases and compared them with the 104 converted cases. We used 31 parameters, including demographics, ultrasonographic findings, and laboratory values, to compare groups. These parameters were later included in a logistic regression analysis to create a statistical model that predicts conversion to open cholecystectomy. RESULTS: Among the 1335 laparoscopically started cases, 104 (7.7%) were converted to open surgery. In our study, we found age, gender, ultrasonographic findings of acute cholecystitis, history of choledocolithiasis, history of abdominal surgery, and alkaline phosphatase (ALP) levels to be significant risk factors. By using a receiver operating characteristic curve, we found that the risk significantly increases after 55 years of age and an ALP over 80 IU/L. DISCUSSION: Using four parameters-age, gender, history of abdominal surgery, and ALP-in our statistical model, we were able to predict the conversion from laparoscopic to open cholecystectomy with 70% sensitivity and 79% specificity. PMID- 27385486 TI - Mutant p53 and mTOR/PKM2 regulation in cancer cells. AB - Mutations of TP53 gene are the most common feature in aggressive malignant cells. In addition to the loss of the tumor suppressive role of wild-type p53, hotspot mutant p53 isoforms display oncogenic proprieties notoriously referred as gain of functions (GOFs) which result in chemoresistance to therapies, genomic instability, aberrant deregulation of cell cycle progression, invasiveness and enhanced metastatic potential, and finally, in patient poor survival rate. The identification of novel functional oncogenic pathways regulated by mutant p53 represent and intriguing topic for emerging therapies against a broad spectrum of cancer types bearing mutant TP53 gene. Mammalian target of rapamycin (mTOR), as well as pyruvate kinase isoform M2 (PKM2) are master regulators of cancer growth, metabolism, and cell proliferation. Herein, we report that GOF mutant R175H and R273H p53 proteins trigger PKM2 phosphorylation on Tyr 105 through the involvement of mTOR signaling. Our data, together with the newly discovered connection between mutant p53 and mTOR stimulation, raise important implications for the potential therapeutic use of synthetic drugs inhibiting mTOR/PKM2 axis in cancer cells bearing mutant TP53 gene. We further hypothesize that mTOR/PKM2 pathway stimulation serves to sustain the oncogenic activity of mutant p53 through both the enhancement of chemoresistance and of aerobic glycolysis of cancer cells. (c) 2016 IUBMB Life, 68(9):722-726, 2016. PMID- 27385485 TI - Citrate Accumulation-Related Gene Expression and/or Enzyme Activity Analysis Combined With Metabolomics Provide a Novel Insight for an Orange Mutant. AB - 'Hong Anliu' (HAL, Citrus sinensis cv. Hong Anliu) is a bud mutant of 'Anliu' (AL), characterized by a comprehensive metabolite alteration, such as lower accumulation of citrate, high accumulation of lycopene and soluble sugars in fruit juice sacs. Due to carboxylic acid metabolism connects other metabolite biosynthesis and/or catabolism networks, we therefore focused analyzing citrate accumulation-related gene expression profiles and/or enzyme activities, along with metabolic fingerprinting between 'HAL' and 'AL'. Compared with 'AL', the transcript levels of citrate biosynthesis- and utilization-related genes and/or the activities of their respective enzymes such as citrate synthase, cytosol aconitase and ATP-citrate lyase were significantly higher in 'HAL'. Nevertheless, the mitochondrial aconitase activity, the gene transcript levels of proton pumps, including vacuolar H(+)-ATPase, vacuolar H(+)-PPase, and the juice sac predominant p-type proton pump gene (CsPH8) were significantly lower in 'HAL'. These results implied that 'HAL' has higher abilities for citrate biosynthesis and utilization, but lower ability for the citrate uptake into vacuole compared with 'AL'. Combined with the metabolites-analyzing results, a model was then established and suggested that the reduction in proton pump activity is the key factor for the low citrate accumulation and the comprehensive metabolite alterations as well in 'HAL'. PMID- 27385487 TI - Lateral Temperature-Gradient Method for High-Throughput Characterization of Material Processing by Millisecond Laser Annealing. AB - A high-throughput method for characterizing the temperature dependence of material properties following microsecond to millisecond thermal annealing, exploiting the temperature gradients created by a lateral gradient laser spike anneal (lgLSA), is presented. Laser scans generate spatial thermal gradients of up to 5 degrees C/MUm with peak temperatures ranging from ambient to in excess of 1400 degrees C, limited only by laser power and materials thermal limits. Discrete spatial property measurements across the temperature gradient are then equivalent to independent measurements after varying temperature anneals. Accurate temperature calibrations, essential to quantitative analysis, are critical and methods for both peak temperature and spatial/temporal temperature profile characterization are presented. These include absolute temperature calibrations based on melting and thermal decomposition, and time-resolved profiles measured using platinum thermistors. A variety of spatially resolved measurement probes, ranging from point-like continuous profiling to large area sampling, are discussed. Examples from annealing of III-V semiconductors, CdSe quantum dots, low-kappa dielectrics, and block copolymers are included to demonstrate the flexibility, high throughput, and precision of this technique. PMID- 27385489 TI - Traumatic dental injury research: on children or with children? AB - BACKGROUND AND AIM: It is widely acknowledged that children should participate in healthcare decisions, service development and even setting research agendas. Dental traumatology is a major component of paediatric dentistry practice and research. However, little is known about young patients' contribution to new knowledge in this field. The aim of the study was to establish the extent to which children are involved in contemporary dental trauma research and to evaluate the quality of the related literature. MATERIAL AND METHODS: A systematic review of the dental trauma literature was conducted from 2006 to 2014. The electronic databases, MEDLINE and Scopus, were used to identify relevant studies. The selected papers were independently examined by five calibrated reviewers. Studies were categorized by the degree of children's involvement and appraised using a validated quality assessment tool. RESULTS: The initial search yielded 4374 papers. After application of the inclusion and exclusion criteria, only 96 studies remained. Research on children accounted for 87.5% of papers, and a proxy was involved in 4.2%. Children were engaged to some degree in only 8.3% of studies, and there were no studies where children were active research participants. In the quality assessment exercise, papers scored, on average, 57% (range = 14-86%). CONCLUSION: There is scope to encourage more active participation of children in dental trauma research in the future. Furthermore, there are some areas where the quality of research could be improved overall. PMID- 27385490 TI - A case of cervicogenic headache caused by C5 nerve root derived shwannoma: Case report. AB - Introduction We report a case of cervicogenic headache caused by an intradural extramedullary tumor of the middle cervical spine, which has not previously been reported. Case presentation The patient was a 73-year-old male who visited a physician for a chief complaint of pain from the left lower jaw to the auricle and occipital region. The headache was induced with retroflexion of the neck. On cervical magnetic resonance imaging, an intradural extramedullary tumor was noted on the left side at the C4/5 level. The intradural tumor, which arose from the C5 nerve root, was excised and the pain was resolved. The pathological diagnosis was schwannoma. Conclusion Previously reported cases of spinal cord tumor-induced cervicogenic headache were due to upper cervical spinal tumors. This is the first report that a middle-lower cervical intradural extramedullary tumor caused cervicogenic headache. PMID- 27385484 TI - Monocyte polarization in children with falciparum malaria: relationship to nitric oxide insufficiency and disease severity. AB - We earlier established that nitric oxide (NO) is protective against severe malaria and that arginine and NO levels are reduced in malaria patients. We now show that an M2-like blood monocyte phenotype is significantly associated with hypoargininemia, NO insufficiency, and disease severity in Tanzanian children with falciparum malaria. Compared to control children (n = 106), children with moderately severe (n = 77) and severe falciparum malaria (n = 129) had significantly higher mononuclear cell arginase 1 mRNA, protein, and enzyme activity; lower NOS2 mRNA; lower plasma arginine; and higher plasma IL-10, IL-13, and IL-4. In addition, monocyte CD206 and CD163 and plasma soluble CD163 were elevated. Multivariate logistic regression analysis revealed a significant correlation of risk of severe malaria with both plasma IL-10 and soluble CD163 levels. Monocyte M2 skewing likely contributes to NO bioinsufficiency in falciparum malaria in children. Treatments that reverse the M2 polarization may have potential as adjunctive treatment for malaria. PMID- 27385491 TI - Modified Guanines as Constituents of Smart Ligands for Nucleic Acid Quadruplexes. AB - Repetitive guanine-rich nucleic acid sequences play a crucial role in maintaining genome stability and the cell life cycle and represent potential targets for regulatory drugs. Recently, it has been demonstrated that guanine-based ligands with a porphyrin core can be used as markers of G-quadruplex assemblies in cell tissues. Herein, model systems of guanine-based ligands are explored by DFT methods. The energies of formation of modified guanine tetrads and those of modified tetrads stacked on the top of natural guanine tetrads have been calculated. The interaction energy has been decomposed into contributions from hydrogen bonding, stacking, and ion coordination and a twist-rise potential energy scan has been performed to find the individual local minima. Energy decomposition analysis reveals the impact of various substituents (F, Cl, Br, I, Me, NMe2 ) on individual energy terms. In addition, cooperative reinforcement in forming the modified and stacked tetrads, as well as the frontier orbitals participating in the hydrogen-bonding framework involving the HOMO-LUMO gap between the occupied sigmaHOMO on the proton-accepting C=O and =N- groups and unoccupied sigmaLUMO on the N-H groups, has been studied. The investigated systems are demonstrated to have a potential in ligand development, mainly due to stacking enhancement compared with natural guanine, which is used as a reference. PMID- 27385492 TI - Stereoselective Organocatalytic Synthesis of alpha,alpha-Difluoro-gamma,gamma Disubstituted Butenals. AB - A highly stereoselective reaction of alpha,alpha-difluoro-gamma,gamma disubstituted butenals 2 bearing two different substituents at the gamma position has been developed with an organocatalytic system of l-proline (30 mol %) and salicylic acid (60 mol %). This novel reaction demonstrated a wide substrate scope and excellent E stereoselectivity in most cases. The obtained difluorinated aldehyde 2a was applied as a useful synthetic precursor for constructing 3,3 disubstituted allylic difluoride moieties. PMID- 27385493 TI - Metallic implant geometry and susceptibility estimation using multispectral B0 field maps. AB - PURPOSE: To estimate the susceptibility and the geometry of metallic implants from multispectral imaging (MSI) information, to separate the metal implant region from the surrounding signal loss region. THEORY AND METHODS: The susceptibility map of signal-void regions is estimated from MSI B0 field maps using total variation (TV) regularized inversion. Voxels with susceptibility estimates above a predetermined threshold are identified as metal. The accuracy of the estimated susceptibility and implant geometry was evaluated in simulations, phantom, and in vivo experiments. RESULTS: The proposed method provided more accurate susceptibility estimation compared with a previous method without TV regularization, in both simulations and phantom experiments. In the phantom experiment where the actual implant was 40% of the signal-void region, the mean estimated susceptibility was close to the susceptibility in literature, and the precision and recall of the estimated geometry was 85% and 93%. In vivo studies in subjects with hip implants also demonstrated that the proposed method can distinguish implants from surrounding low-signal tissues, such as cortical bone. CONCLUSION: The proposed method can improve the delineation of metallic implant geometry by distinguishing metal voxels from artificial signal voids and low-signal tissues by estimating the susceptibility maps. Magn Reson Med 77:2402 2413, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27385494 TI - Improving outcomes for Aboriginal and Torres Strait Islander people with cancer requires a systematic approach to understanding patients' experiences of care. AB - Indigenous Australians experience a greater burden of cancer than other Australians, but there is little systematic information about their experiences of cancer care. Patient-centred care is increasingly recognised as one of the core domains of quality care, alongside clinical effectiveness and patient safety. Qualitative studies have identified significant issues relating to Indigenous patients' experiences of cancer care, but these data are often insufficient to inform and evaluate health service improvement. We need to establish appropriate methods that will lead to systematic, routinely collected, accurate, population-based data on the experiences of care of Indigenous people with cancer, and determine how best to translate these data into improvements in the delivery of care to this population. Genuine Indigenous leadership and involvement will be necessary, with the whole approach underpinned by the primary aim of improving health outcomes for this population. PMID- 27385495 TI - Correlating clinical and radiological assessment of joints in haemophilia: results of a cross sectional study. AB - OBJECTIVES: This study was undertaken to determine the correlation between the radiological changes in haemophilic arthropathy [X-ray, Ultrasound (US) and MRI] and clinical assessment as determined by the Hemophilia Joint Health Score (HJHS); and to document the US and MRI changes in joints that appear normal on plain X-ray and clinical evaluation. MATERIALS AND METHODS: Of 55 study joints (22 knees and 33 ankles) in 51 patients with haemophilia/von Willebrand disease, with a median age of 15 years (range: 5-17) were assessed using X-rays (Pettersson score) and clinical examination (HJHS) at two centres (Toronto, Canada; Vellore, India). MRI and ultrasonographic scoring was done through a consensus assessment by imagers at both centres using the IPSG MRI and US scores. RESULTS: The HJHS had a good correlation with the Pettersson score (rs = 0.66). Though the HJHS had moderate correlation with the osteochondral component of the MRI and US scores (rs 0.51, 0.45 respectively), its correlation with the soft tissue component was poor (rs 0.19; 0.26 respectively). Of the 18 joints with a Pettersson score of zero, 88.9% had changes that were detected clinically by the HJHS. Osteochondral abnormalities were identified in 38.9% of these joints by the MRI, while US images of the same joints were deemed abnormal in 83.3% by the current criteria. US identified haemosiderin and other soft tissue changes in all of the joints, while the same changes were noted in 94.4% of these joints on MRI. There were four joints with a HJHS of zero, all of which had soft tissue changes on MRI (score 1-7) and US (score 2-7). Osteochondral changes were detected in three of these joints by US and in 2 by MRI. There were four joints with an MRI score of 0-1 that had significant US scores (3-5) and HJHS scores (0-6). CONCLUSION: US and MRI are able to identify pathological changes in joints with normal X-ray imaging and clinical examination. However, further studies are required to be able to differentiate early abnormalities from normal. Clinical (HJHS) and radiological assessment (US/MRI) provide complimentary information and should be considered conjointly in the assessment of early joint arthropathy. PMID- 27385496 TI - Thermoelectric plastics: from design to synthesis, processing and structure property relationships. AB - Thermoelectric plastics are a class of polymer-based materials that combine the ability to directly convert heat to electricity, and vice versa, with ease of processing. Potential applications include waste heat recovery, spot cooling and miniature power sources for autonomous electronics. Recent progress has led to surging interest in organic thermoelectrics. This tutorial review discusses the current trends in the field with regard to the four main building blocks of thermoelectric plastics: (1) organic semiconductors and in particular conjugated polymers, (2) dopants and counterions, (3) insulating polymers, and (4) conductive fillers. The design and synthesis of conjugated polymers that promise to show good thermoelectric properties are explored, followed by an overview of relevant structure-property relationships. Doping of conjugated polymers is discussed and its interplay with processing as well as structure formation is elucidated. The use of insulating polymers as binders or matrices is proposed, which permit the adjustment of the rheological and mechanical properties of a thermoelectric plastic. Then, nanocomposites of conductive fillers such as carbon nanotubes, graphene and inorganic nanowires in a polymer matrix are introduced. A case study examines poly(3,4-ethylenedioxythiophene) (PEDOT) based materials, which up to now have shown the most promising thermoelectric performance. Finally, a discussion of the advantages provided by bulk architectures e.g. for wearable applications highlights the unique advantages that thermoelectric plastics promise to offer. PMID- 27385497 TI - Morphological and Hemodynamic Effectiveness of Stenting for Pulmonary Artery Stenosis - Subanalysis of JPIC Stent Survey. AB - BACKGROUND: Percutaneous stenting for branch pulmonary artery stenosis is an established interventional choice in congenital heart disease. The apparent morphologic change in the vessel diameter often differs from the hemodynamic result. METHODS AND RESULTS: We performed a subanalysis of the data from the Japanese Society of Pediatric Interventional Cardiology (JPIC) stent survey. The factors that may have contributed to morphologic effectiveness included reference vessel diameter (RVD), minimum lumen diameter (MLD) and percent diameter stenosis (%DS) and the relation between morphologic and hemodynamic effectiveness was evaluated in 206 lesions treated with stenting. We defined a "50% increase in MLD" as "morphologically effective", while "achievement of either a reduced pressure gradient greater than 50% or an increase of perfusion ratio to the affected side to the contralateral side greater than 20%" as "hemodynamically effective". Morphologic effectiveness was achieved in 84% of patients. Before stenting, %DS was significantly larger, while RVD was smaller in the "effective" group than in the "non-effective" group. The cutoff value for effective stenting was 51% for %DS and 14.7 mm for RVD before stenting. Hemodynamic effectiveness was obtained more often in the "morphologic effective" group. CONCLUSIONS: RVD and %DS were the 2 main contributors to acute morphologic effectiveness. There was a significant relationship between "morphologic effectiveness" and "hemodynamic effectiveness", judging from increased perfusion of the affected lung and/or decreased pressure gradient. (Circ J 2016; 80: 1852-1856). PMID- 27385498 TI - Relationship of Left Ventricular Diastolic Function to Obesity and Overweight in a Japanese Population With Preserved Left Ventricular Ejection Fraction. AB - BACKGROUND: Obesity has been found to be associated with future development of diastolic heart failure. Other evidence has indicated that the effect of obesity on left ventricular (LV) mass varies among ethnicities. However, there are few data on the relationship between body mass index (BMI) and LV diastolic dysfunction in the Japanese population. METHODS AND RESULTS: We performed echocardiography in 788 subjects without valvular disease or LV systolic dysfunction. They were divided into 3 groups by BMI: normal weight, overweight, and obese. We used multivariable linear regression analysis to assess the clinical variables associated with diastolic parameters, including BMI. We also assessed the risk of diastolic dysfunction associated with BMI using multivariable logistic models. Overweight and obese subjects had significantly worse LV diastolic function and greater LV mass than normal weight subjects. In the multivariable analysis, BMI was independently associated with diastolic parameters. Furthermore, after adjusting for clinical factors, the increased risks of diastolic dysfunction in overweight subjects (adjusted odds ratio: 2.02, 95% confidence interval 1.21-3.36) and obese subjects (4.85, 3.36-16.27) were greater than those previously observed in Western populations. CONCLUSIONS: The Japanese population might be more susceptible than Western subjects to the effect of BMI on LV diastolic function. Differences between ethnicities should be taken into consideration in strategies for the prevention of diastolic heart failure. (Circ J 2016; 80: 1951-1956). PMID- 27385499 TI - Transtubular Potassium Concentration Gradient as a Surrogate Measure of Arterial Underfilling in Acute Decompensated Heart Failure. AB - BACKGROUND: The monitoring of tissue hypoperfusion and the subsequent neurohumoral activation (ie, arterial underfilling) during decongestion is important for the management of acute decompensated heart failure (ADHF). The transtubular potassium concentration gradient (TTKG) has been reported to be a marker of renal aldosterone bioactivity. This study tested the hypothesis that TTKG can be a surrogate of arterial underfilling in patients with ADHF. METHODS AND RESULTS: We measured TTKG at discharge in 100 ADHF patients. The primary outcome measure was the occurrence of tissue hypoperfusion events (defined according to the "Cold Modified 2014" definition criteria) within 1 month after discharge. The secondary outcome measure was the occurrence of cardiac death or ADHF readmission within 3 months after discharge. On receiver operating characteristic curve analysis, TTKG predicted tissue hypoperfusion events with high accuracy (C-statistic, 0.889) for a cut-off of 6.0. Multivariate Cox regression analyses demonstrated independent relationships between TTKG and both the primary and secondary outcomes. CONCLUSIONS: TTKG has utility as a surrogate of arterial underfilling, and spot TTKG at discharge may be a prognostic marker in ADHF patients. (Circ J 2016; 80: 1965-1970). PMID- 27385500 TI - Overview of the 80(th) Annual Scientific Meeting of the Japanese Circulation Society - The Past, Present and Future of Cardiovascular Medicine in Japan - - The 5(th) Anniversary of the Great East Japan Earthquake. AB - The 80(th)Annual Scientific Meeting of the Japanese Circulation Society was held in Sendai, Japan, on March 18-20, 2016, which coincided with the 5(th)anniversary of the Great East Japan Earthquake that hit the Tohoku area on March 11, 2011. Thus, the main themes for this meeting were "The Past, Present and Future of Cardiovascular Medicine in Japan" and "The 5(th)Anniversary of the Great East Japan Earthquake". Despite the provincial location, approximately 15,000 people attended during the 3-day meeting, and there were in-depth discussions in each of the various sessions on these themes. Especially, to our great pleasure, the Japanese Royals, Emperor Akihito and Empress Michiko, kindly visited the panel exhibition of the Great East Japan Earthquake and spoke words of appreciation to us. The meeting successfully completed and we sincerely appreciate the great cooperation and support from all affiliates. (Circ J 2016; 80: 1689-1694). PMID- 27385501 TI - A Multifunctional Biomaterial with NIR Long Persistent Phosphorescence, Photothermal Response and Magnetism. AB - There are many reports on long persistent phosphors (LPPs) applied in bioimaging. However, there are few reports on LPPs applied in photothermal therapy (PTT), and an integrated system with multiple functions of diagnosis and therapy. In this work, we fabricate effective multifunctional phosphors Zn3 Ga2 SnO8 : Cr(3+) , Nd(3+) , Gd(3+) with NIR persistent phosphorescence, photothermal response and magnetism. Such featured materials can act as NIR optical biolabels and magnetic resonance imaging (MRI) contrast agents for tracking the early cancer cells, but also as photothermal therapeutic agent for killing the cancer cells. This new multifunctional biomaterial is expected to open a new possibility of setting up an advanced imaging-guided therapy system featuring a high resolution for bioimaging and low side effects for the photothermal ablation of tumors. PMID- 27385502 TI - Effects of topical combinations of clonidine and pentoxifylline on capsaicin induced allodynia and postcapsaicin tourniquet-induced pain in healthy volunteers: a double-blind, randomized, controlled study. AB - This double-blind randomized controlled study was designed to evaluate the analgesic effects of topical treatments with clonidine (CLON) and pentoxifylline (PTX) tested alone or as low- and high-dose combinations in a human experimental model of pain. Of 69 healthy subjects aged 18 to 60 years, 23 each were randomly allocated to low-dose (0.04% + 2%) and high-dose (0.1% + 5%) CLON + PTX groups. Both of these groups also received their corresponding placebos in one of 2 treatment periods separated by at least 48 hours. Twenty-three additional subjects received either CLON (0.1%) or PTX (5%) as single drug treatments, in each of 2 treatment periods. Assessment of analgesic efficacy was based on allodynic effects of previous intraepidermal capsaicin injection, as well as postcapsaicin tourniquet-induced pain 50 minutes following capsaicin injection. Visual Analogue Scale (VAS) ratings of pain intensity and the area of dynamic mechanical allodynia were the primary outcome measures, whereas area of punctate mechanical allodynia (PMA) served as a secondary outcome measure. Topical treatments with high- or low-dose combinations significantly reduced VAS ratings compared with corresponding placebo treatments throughout the period of postcapsaicin tourniquet-induced pain. Importantly, the high-dose combination produced lower VAS ratings than CLON alone, which were lower than PTX alone. Results also revealed significant inhibition of postcapsaicin dynamic mechanical allodynia and PMA for the high-dose combination compared with placebo, and of PMA for CLON compared with the low-dose combination. Hence, the present data are supportive of further clinical investigation of the high-dose topical combination of CLON + PTX in complex regional pain syndrome and neuropathic pain patients, for which our preclinical data predict efficacy. PMID- 27385503 TI - Why does depression promote long-term opioid use? PMID- 27385505 TI - Illness perceptions of leprosy-cured individuals in Surinam with residual disfigurements - "I am cured, but still I am ill". AB - Objective Leprosy has rarely been the subject of health psychology research despite its substantial impact. Our aim was to explore illness perceptions in patients and their health care providers in Surinam. The Common Sense Model (CSM) was the guiding theoretical model. Design Patients with biomedically cured leprosy and their health care providers completed the B-IPQ and took part in semi structured interviews. The literature on illness perceptions in patients with leprosy was reviewed. Main outcome measures Patients' B-IPQ scores were compared with samples of patients with other (chronic) illnesses, and with health care providers completing the questionnaire as if they were visibly disfigured patients. Quotations from the semi-structured interviews were used to contextualise the illness perceptions. Results Patients' B-IPQ scores reflected the chronic nature of leprosy and were comparable with those with other chronic illnesses. Health care providers perceived leprosy to have a greater negative impact than did the patients. Perceived understanding of causes differed considerably between patients and health care providers. Conclusion Leprosy continues to be experienced as an illness with major psychological and social consequences such as stigmatisation, even after biomedical cure. Interventions that target patients, health care providers, and society at large may help reduce perceived shame and stigma. The CSM is a helpful theoretical model in studying this population. PMID- 27385506 TI - Static Magnetowetting of Ferrofluid Drops. AB - We report results of a comprehensive study of the wetting properties of sessile drops of ferrofluid water solutions at various concentrations deposited on flat substrates and subjected to the action of permanent magnets of different sizes and strengths. The amplitude and the gradient of the magnetic field experienced by the ferrofluid are changed by varying the magnets and their distance to the surface. Magnetic forces up to 100 times the gravitational one and magnetic gradients up to 1 T/cm are achieved. A rich phenomenology is observed, ranging from flattened drops caused by the magnetic attraction to drops extended normally to the substrate because of the normal traction of the magnetic field. We find that the former effect can be conveniently described in terms of an effective Bond number that compares the effective drop attraction with the capillary force, whereas the drop's vertical elongation is effectively expressed by a dimensionless number S, which compares the pressure jump at the ferrofluid interface because of the magnetization with the capillary pressure. PMID- 27385508 TI - Sensitivity of tissue properties derived from MRgFUS temperature data to input errors and data inclusion criteria: ex vivo study in porcine muscle. AB - This study evaluates the sensitivity of two magnetic resonance-guided focused ultrasound (MRgFUS) thermal property estimation methods to errors in required inputs and different data inclusion criteria. Using ex vivo pork muscle MRgFUS data, sensitivities to required inputs are determined by introducing errors to ultrasound beam locations (r error = -2 to 2 mm) and time vectors (t error = 2.2 to 2.2 s). In addition, the sensitivity to user-defined data inclusion criteria is evaluated by choosing different spatial (r fit = 1-10 mm) and temporal (t fit = 8.8-61.6 s) regions for fitting. Beam location errors resulted in up to 50% change in property estimates with local minima occurring at r error = 0 and estimate errors less than 10% when r error < 0.5 mm. Errors in the time vector led to property estimate errors up to 40% and without local minimum, indicating the need to trigger ultrasound sonications with the MR image acquisition. Regarding the selection of data inclusion criteria, property estimates reached stable values (less than 5% change) when r fit > 2.5 * FWHM, and were most accurate with the least variability for longer t fit. Guidelines provided by this study highlight the importance of identifying required inputs and choosing appropriate data inclusion criteria for robust and accurate thermal property estimation. Applying these guidelines will prevent the introduction of biases and avoidable errors when utilizing these property estimation techniques for MRgFUS thermal modeling applications. PMID- 27385507 TI - An investigation of the antibacterial ability and cytotoxicity of a novel cu bearing 317L stainless steel. AB - In order to solve the challenging problem of microbial infections caused by microorganisms on medical implants, it is imperative to develop novel antimicrobial biomaterials. This work demonstrated that 317L-Cu stainless steel (SS), created by adding copper through a solution and aging heat treatment process, exhibited good antibacterial properties against staphylococcus aureus, achieving 2 log reduction of planktonic cells after 5 days of incubation. In this study, the antibacterial test was performed using the plate count method, the fluorescence cell staining method and the quantitative polymerase chain reaction (qPCR) method. It is well known that a high concentration of copper ion can lead to cytotoxicity. This work explored the cytotoxicity of 317L-Cu SS through real time cell analysis (RTCA). Experimental results demonstrated that the 317L-Cu SS possessed a satisfactory antibacterial ability against S. aureus, and the antibacterial rate based on the reduction of sessile cell count reached 98.3% after 24-hour treatment. The bacterial adhesion and the biofilm thickness were considerably reduced by the 317L-Cu SS. The results of RTCA suggested that 317L Cu SS did not introduce cytotoxicity to mouse cells, indicating its suitability as a medical implant material. PMID- 27385510 TI - Uncoupling proteins of invertebrates: A review. AB - Uncoupling proteins (UCPs) mediate inducible proton conductance in the mitochondrial inner membrane. Herein, we summarize our knowledge regarding UCPs in invertebrates. Since 2001, the presence of UCPs has been demonstrated in nematodes, mollusks, amphioxi, and insects. We discuss the following important issues concerning invertebrate UCPs: their evolutionary relationships, molecular and functional properties, and physiological impact. Evolutionary analysis indicates that the branch of vertebrate and invertebrate UCP4-5 diverged early in the evolutionary process prior to the divergence of the animal groups. Several proposed physiological roles of invertebrate UCPs are energy control, metabolic balance, and preventive action against oxidative stress. (c) 2016 IUBMB Life, 68(9):691-699, 2016. PMID- 27385509 TI - Toothbrushing, Blood Glucose and HbA1c: Findings from a Random Survey in Chinese Population. AB - Both diabetes and periodontal disease are prevalent in China. Poor oral hygiene practice is the major cause of periodontal disease. An association between oral hygiene practice and blood glucose level was reported in individuals with diabetes, but not in the general population. We examined the association in a population-based random survey recruiting 2,105 adults without previously diagnosed diabetes in Chongqing city, China. Plasma glucose and hemoglobin A1c (HbA1c) were measured, and a 2-hour oral glucose tolerance test was conducted for each respondent. Self-reported toothbrushing frequency was used as a proxy for oral hygiene practice. In a linear model controlling for potential confounders (demographic characteristics, socio-economic status, lifestyle risk factors, BMI, dental visit frequency, etc.), urban residents who barely brushed their teeth had an increase of 0.50 (95% CI: 0.10-0.90) mmol/L in fasting plasma glucose, and an increase of 0.26% (0.04-0.47%) in HbA1c, relative to those brushing >=twice daily; for rural residents, the effects were 0.26 (0.05-0.48) mmol/L in fasting plasma glucose and 0.20% (0.09-0.31%) in HbA1c. Individuals with better oral practice tended to have lower level of blood glucose and HbA1c. Establishing good oral health behavioral habits may be conducive to diabetes prevention and control in the general population. PMID- 27385512 TI - Abnormal spermatogenesis and male infertility in testicular zinc finger protein Zfp318-knockout mice. AB - Zfp318, a mouse gene with a Cys2/His2 zinc finger motif, is mainly expressed in germ cells in the testis. It encodes two alternative transcripts, which regulate androgen receptor-mediated transcriptional activation or repression by overexpression of them. However, the role of Zfp318 is still obscure in vivo, especially in spermatogenesis. To elucidate the role of Zfp318 during gamete production, we established a knockout mouse line. Zfp318-null male mice exhibited infertility, whereas Zfp318-null female mice displayed normal fertility. ZFP318 was expressed during multiple stages of spermatogenesis, from spermatocytes to round spermatids. The nuclei of secondary spermatocytes showed high levels of expression. Histological analysis and quantitative analysis of DNA content showed decreased numbers of both spermatids in the seminiferous tubules and mature spermatozoa in the epididymides of Zfp318-null mice. These results suggest that Zfp318 is expressed as a functional protein in testicular germ cells and plays an important role in meiosis during spermatogenesis. PMID- 27385511 TI - Age, time living with diagnosed HIV infection, and self-rated health. AB - OBJECTIVES: An increasing proportion of people living with HIV are older adults, who may require specialized care. Adverse physical and psychological effects of HIV infection may be greatest among older people or those who have lived longer with HIV. METHODS: The ASTRA study is a cross-sectional questionnaire study of 3258 HIV-diagnosed adults (2248 men who have sex with men, 373 heterosexual men and 637 women) recruited from UK clinics in 2011-2012. Associations of age group with physical symptom distress (significant distress for at least one of 26 symptoms), depression and anxiety symptoms (scores >= 10 on PHQ-9 and GAD-7, respectively), and health-related functional problems (problems on at least one of three domains of the Euroqol 5D-3L)) were assessed, adjusting for time with diagnosed HIV infection, gender/sexual orientation and ethnicity. RESULTS: The age distribution of participants was: < 30 years, 5%; 30-39 years, 23%; 40-49 years, 43%; 50-59 years, 22%; and >= 60 years, 7%. Overall prevalences were: physical symptom distress, 56%; depression symptoms, 27%; anxiety symptoms, 22%; functional problems, 38%. No trend was found in the prevalence of physical symptom distress with age [adjusted odds ratio (OR) for trend across age groups, 0.96; 95% confidence interval (CI) 0.89, 1.04; P = 0.36]. The prevalence of depression and anxiety symptoms decreased with age [adjusted OR 0.86 (95% CI 0.79, 0.94; P = 0.001) and adjusted OR 0.85 (95% CI 0.77, 0.94; P = 0.001), respectively], while that of functional problems increased (adjusted OR 1.28; 95% CI 1.17, 1.39; P < 0.001). In contrast, a longer time with diagnosed HIV infection was strongly and independently associated with a higher prevalence of symptom distress, depression symptoms, anxiety symptoms, and functional problems (P < 0.001 for trends, adjusted analysis). CONCLUSIONS: Among people living with HIV, although health-related functional problems were more common with older age, physical symptom distress was not, and mental health was more favourable. These results suggest that a longer time with diagnosed HIV infection, rather than age, is the dominating factor contributing to psychological morbidity and lower quality of life. PMID- 27385513 TI - Decoupling the effects of confinement and passivation on semiconductor quantum dots. AB - Semiconductor (SC) quantum dots (QDs) have recently been fabricated by both chemical and plasma techniques for specific absorption and emission of light. Their optical properties are governed by the size of the QD and the chemistry of any passivation at their surface. Here, we decouple the effects of confinement and passivation by utilising DC magnetron sputtering to fabricate SC QDs in a perfluorinated polyether oil. Very high band gaps are observed for fluorinated QDs with increasing levels of quantum confinement (from 4.2 to 4.6 eV for Si, and 2.5 to 3 eV for Ge), with a shift down to 3.4 eV for Si when oxygen is introduced to the passivation layer. In contrast, the fluorinated Si QDs display a constant UV photoluminescence (3.8 eV) irrespective of size. This ability to tune the size and passivation independently opens a new opportunity to extending the use of simple semiconductor QDs. PMID- 27385514 TI - Unprecedented Dual Light-Switching Response of a Metal Dipyridophenazine Complex toward Amyloid-beta Aggregation. AB - Probes for monitoring protein aggregation with a variety of photophysical properties are of importance for the fundamental understanding of the aggregation process as well as for drug discovery. In this manuscript we report the photoluminescence response of the metal dipyridophenazine complex [Re(CO)3(dppz)(Py)](+) in the presence of aggregated Abeta. [Re(CO)3(dppz)(Py)](+) shows an instantaneous increase in photoluminescence with fibrillar Abeta (primary light-switching), and an unprecedented further increase in photoluminescence upon light irradiation at 362 nm (secondary light switching). The total increase in photoluminescence amounts to 105-fold, which we show can be used to monitor Abeta aggregation in real time. PMID- 27385515 TI - Psychometric Properties of the Dutch Version of the Signs of Depression Scale. AB - The early detection of depression after stroke is essential for the optimization of recovery in aphasic stroke patients. The purpose of this study was to evaluate the psychometric properties of the Signs of Depression Scale (SODS), a non language-based screening instrument. We conducted a cross-sectional study in a sample of 58 stroke patients in a rehabilitation center. The internal consistency and interrater reliability were good (alpha = .71 and intraclass correlation coefficient [ICC] = .79). The pre-defined hypotheses confirmed the construct validity, and the correlation between the SODS and the Patient Health Questionnaire-9 (PHQ-9) was moderate ( rb = .32). At a cutoff score of >=1, the sensitivity was 0.80, and the specificity was 0.39. These findings indicate that the SODS is appropriate to screen for depressive symptoms and can be used by nurses to identify symptoms of depression in patients with aphasia who require further assessment. PMID- 27385516 TI - Variation in health warning effectiveness on cigarette packs: a need for regulation? AB - The Tobacco Products Directive allows the possibility of strategic placement of health warnings on cigarette packs by manufacturers to reduce overall warning effectiveness. Information regarding health warning effectiveness was assessed in an online survey, and the prevalence of warnings on cigarette packs was assessed in a shop survey. Although we find no evidence of a strong correlation between health warning effectiveness ratings and their frequency on cigarette packs (r = 0.17, P = 0.56), there may be other ways this possibility is exploited. We suggest that this potential loophole is addressed and monitoring of the placement of health warnings on cigarette packs is continued. PMID- 27385517 TI - The integrative role of orexin/hypocretin neurons in nociceptive perception and analgesic regulation. AB - The level of wakefulness is one of the major factors affecting nociception and pain. Stress-induced analgesia supports an animal's survival via prompt defensive responses against predators or competitors. Previous studies have shown the pharmacological effects of orexin peptides on analgesia. However, orexin neurons contain not only orexin but also other co-transmitters such as dynorphin, neurotensin and glutamate. Thus, the physiological importance of orexin neuronal activity in nociception is unknown. Here we show that adult-stage selective ablation of orexin neurons enhances pain-related behaviors, while pharmacogenetic activation of orexin neurons induces analgesia. Additionally, we found correlative activation of orexin neurons during nociception using fiber photometry recordings of orexin neurons in conscious animals. These findings suggest an integrative role for orexin neurons in nociceptive perception and pain regulation. PMID- 27385518 TI - LysGH15 kills Staphylococcus aureus without being affected by the humoral immune response or inducing inflammation. AB - The lysin LysGH15, derived from the staphylococcal phage GH15, exhibits a wide lytic spectrum and highly efficient lytic activity against methicillin-resistant Staphylococcus aureus (MRSA). Here, we found that LysGH15 did not induce resistance in MRSA or methicillin-sensitive S. aureus (MSSA) strains after repeated treatment. Although LysGH15 triggered the generation of LysGH15-specific antibodies in mice, these antibodies did not block lytic activity in vitro (nor the binding capacity of LysGH15). More importantly, when the antibody titre was highest in mice immunized with LysGH15, a single intravenous injection of LysGH15 was sufficient to protect mice against lethal infection with MRSA. These results indicated that LysGH15-specific antibodies did not affect the killing efficiency of LysGH15 against MRSA in vitro or in vivo. LysGH15 also reduced pro inflammatory cytokines in mice with lethal infections. Furthermore, a high-dose LysGH15 injection did not cause significant adverse effects or pathological changes in the main organs of treated animals. These results provide further evidence for the administration of LysGH15 as an alternative strategy for the treatment of infections caused by MRSA. PMID- 27385520 TI - Allergic contact cheilitis caused by menthol in toothpaste and throat medication: a case report. PMID- 27385519 TI - The reproducibility of nickel, cobalt and chromate sensitization in patients tested at least twice in the period 1992-2014 with TRUE Test(r). PMID- 27385521 TI - Assessment of chromium(VI) release from 848 jewellery items by use of a diphenylcarbazide spot test. PMID- 27385522 TI - ESSCA results with nickel, cobalt and chromium, 2009-2012. PMID- 27385523 TI - Allergic contact dermatitis caused by rotigotine in a transdermal therapeutic system. PMID- 27385525 TI - Fixed alcohol eruption. PMID- 27385524 TI - Contact dermatitis caused by pharmaceutical ointments containing 'ozonated' olive oil. PMID- 27385527 TI - Direct Structural Identification of Gas Induced Gate-Opening Coupled with Commensurate Adsorption in a Microporous Metal-Organic Framework. AB - Gate-opening is a unique and interesting phenomenon commonly observed in flexible porous frameworks, where the pore characteristics and/or crystal structures change in response to external stimuli such as adding or removing guest molecules. For gate-opening that is induced by gas adsorption, the pore-opening pressure often varies for different adsorbate molecules and, thus, can be applied to selectively separate a gas mixture. The detailed understanding of this phenomenon is of fundamental importance to the design of industrially applicable gas-selective sorbents, which remains under investigated due to the lack of direct structural evidence for such systems. We report a mechanistic study of gas induced gate-opening process of a microporous metal-organic framework, [Mn(ina)2 ] (ina=isonicotinate) associated with commensurate adsorption, by a combination of several analytical techniques including single crystal X-ray diffraction, in situ powder X-ray diffraction coupled with differential scanning calorimetry (XRD DSC), and gas adsorption-desorption methods. Our study reveals that the pronounced and reversible gate opening/closing phenomena observed in [Mn(ina)2 ] are coupled with a structural transition that involves rotation of the organic linker molecules as a result of interaction of the framework with adsorbed gas molecules including carbon dioxide and propane. The onset pressure to open the gate correlates with the extent of such interaction. PMID- 27385528 TI - A qualitative investigation of decision making during help-seeking for adult hearing loss. AB - OBJECTIVE: The Any Qualified Provider framework in the National Health Service has changed the way adult audiology services are offered in England. Under the new rules, patients are being offered a choice in geographical location and audiology provider. This study aimed to explore how choices in treatment are presented and to identify what information patients need when they are seeking help with hearing loss. DESIGN: This study adopted qualitative methods of ethnographic observations and focus group interviews to identify information needed prior to, and during, help-seeking. Observational data and focus group data were analysed using the constant comparison method of grounded theory. STUDY SAMPLE: Participants were recruited from a community Health and Social Care Trust in the west of England. This service incorporates both an Audiology and a Hearing Therapy service. Twenty seven participants were involved in focus groups or interviews. RESULTS: Participants receive little information beyond the detail of hearing aids. Participants report little information that was not directly related to uptake of hearing aids. CONCLUSIONS: Participant preferences were not explored and limited information resulted in decisions that were clinician-led. The gaps in information reflect previous data on clinician communication and highlight the need for consistent information on a range of interventions to manage hearing loss. PMID- 27385529 TI - A New Freshwater Naked Lobose Amoeba Korotnevella venosa n. sp. (Amoebozoa, Discosea). AB - A new freshwater species of naked lobose amoebae Korotnevella venosa n. sp. isolated from freshwater pond in St. Petersburg, Russia was studied with light and transmission electron microscopy. Basket scales of this species have six vertical columns supporting perforated rim. The latter has tongue-like broadening with membranous region. Vertical columns bifurcate at both ends so that neighboring columns are connected by their bifurcations forming combined structure. Basket scales of K. venosa are similar to those of Korotnevella hemistylolepis in having six full-length vertical columns and perforated rim. At the same time, they are different in having tongue-like broadening of perforated rim with membranous region and absence of six half-length columns and an intermediate crosspiece. Phylogenetic trees based on 18S rDNA gene placed K. venosa either at the base of the whole Korotnevella clade, next to K. hemistylolepis, or as a sister to the clade comprising Korotnevella species with latticework basket in large scales. PMID- 27385530 TI - Characterization of perfluorocarbon relaxation times and their influence on the optimization of fluorine-19 MRI at 3 tesla. AB - PURPOSE: To characterize and optimize 19 F MRI for different perfluorocarbons (PFCs) at 3T and quantify the loss of acquisition efficiency as a function of different temperature and cellular conditions. METHODS: The T1 and T2 relaxation times of the commonly used PFCs perfluoropolyether (PFPE), perfluoro-15-crown-5 ether (PFCE), and perfluorooctyl bromide (PFOB) were measured in phantoms and in several different conditions (cell types, presence of fixation agent, and temperatures). These relaxation times were used to optimize pulse sequences through numerical simulations. The acquisition efficiency in each cellular condition was then determined as the ratio of the signal after optimization with the reference relaxation times and after optimization with its proper relaxation times. Finally, PFC detection limits were determined. RESULTS: The loss of acquisition efficiency due to parameter settings optimized for the wrong temperature and cellular condition was limited to 13%. The detection limits of all PFCs were lower at 24 degrees C than at 37 degrees C and varied from 11.8 +/- 3.0 mM for PFCE at 24 degrees C to 379.9 +/- 51.8 mM for PFOB at 37 degrees C. CONCLUSION: Optimizing 19 F pulse sequences with a known phantom only leads to moderate loss in acquisition efficiency in cellular conditions that might be encountered in in vivo and in vitro experiments. Magn Reson Med 77:2263-2271, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27385531 TI - Low amplitude of inverted T-waves in lead aVR characterise patients with arrhythmogenic cardiomyopathy. PMID- 27385532 TI - Room-temperature and temperature-dependent QSRR modelling for predicting the nitrate radical reaction rate constants of organic chemicals using ensemble learning methods. AB - Experimental determinations of the rate constants of the reaction of NO3 with a large number of organic chemicals are tedious, and time and resource intensive; and the development of computational methods has widely been advocated. In this study, we have developed room-temperature (298 K) and temperature-dependent quantitative structure-reactivity relationship (QSRR) models based on the ensemble learning approaches (decision tree forest (DTF) and decision treeboost (DTB)) for predicting the rate constant of the reaction of NO3 radicals with diverse organic chemicals, under OECD guidelines. Predictive powers of the developed models were established in terms of statistical coefficients. In the test phase, the QSRR models yielded a correlation (r(2)) of >0.94 between experimental and predicted rate constants. The applicability domains of the constructed models were determined. An attempt has been made to provide the mechanistic interpretation of the selected features for QSRR development. The proposed QSRR models outperformed the previous reports, and the temperature dependent models offered a much wider applicability domain. This is the first report presenting a temperature-dependent QSRR model for predicting the nitrate radical reaction rate constant at different temperatures. The proposed models can be useful tools in predicting the reactivities of chemicals towards NO3 radicals in the atmosphere, hence, their persistence and exposure risk assessment. PMID- 27385533 TI - MicroRNA-Responsive Drug Release System for Selective Fluorescence Imaging and Photodynamic Therapy In Vivo. AB - Photodynamic therapy (PDT) is a noninvasive strategy to treat diseases by light triggered activation of a photosensitizer (PS). One aim of the recent researches on PDT is to overcome the limitation of conventional PDT by improving selective activation of PS on targeted region. Here, a microRNA (miRNA)-responsive drug activation system is developed which focuses on the role of endogenous miRNA as an internal cancer specific stimulus for initiating drug release in cancer treatment. The present system consists of PS chlorin e6 (Ce6) conjugated to peptide nucleic acid (PNA) having complementary sequence to cancer specific miRNA and dextran coated reduced graphene oxide nanocolloid (Dex-RGON). In the presence of oncogenic miR-21 in cancer cells, Ce6-PNA drug gets hybridized with miR-21, resulting in the release of Ce6-PNA from Dex-RGON and subsequent recovery of Ce6 fluorescence and activation of Ce6 as a photosensitizer under near IR irradiation. It is demonstrated that the Ce6-PNA/Dex-RGON complex shows sequence specific fluorescence in response to miR-21 and selective cytotoxic effect for tumor growth inhibition. The present study will pave a new way for utilizing PDT in cancer treatment with tightly regulated activation of a photosensitizer by oncogenic miRNA as an internal stimulus to reduce potential risk associated with conventional PDT. PMID- 27385535 TI - Flexible nasendoscopy: the use of smartphones as an immediate light source. PMID- 27385534 TI - cis Retinol oxidation regulates photoreceptor access to the retina visual cycle and cone pigment regeneration. AB - KEY POINTS: This study explores the nature of the cis retinol that Muller cells in the retina provide to cones for the regeneration of their visual pigment. We report that the retina visual cycle provides cones exclusively with 11-cis chromophore in both salamander and mouse and show that this selectivity is dependent on the 11-cis-specific cellular retinaldehyde binding protein (CRALBP) present in Muller cells. Even though salamander blue cones and green rods share the same visual pigment, only blue cones but not green rods are able to dark adapt in the retina following a bleach and to use exogenous 9-cis retinol for pigment regeneration, suggesting that access to the retina visual cycle is cone specific and pigment-independent. Our results show that the retina produces 11 cis retinol that can be oxidized and used for pigment regeneration and dark adaptation selectively in cones and not in rods. ABSTRACT: Chromophore supply by the retinal Muller cells (retina visual cycle) supports the efficient pigment regeneration required for cone photoreceptor function in bright light. Surprisingly, a large fraction of the chromophore produced by dihydroceramide desaturase-1, the putative all-trans retinol isomerase in Muller cells, appears to be 9-cis retinol. In contrast, the canonical retinal pigment epithelium (RPE) visual cycle produces exclusively 11-cis retinal. Here, we used the different absorption spectra of 9-cis and 11-cis pigments to identify the isoform of the chromophore produced by the visual cycle of the intact retina. We found that the spectral sensitivity of salamander and mouse cones dark-adapted in the isolated retina (with only the retina visual cycle) was similar to that of cones dark adapted in the intact eye (with both the RPE and retina visual cycles) and consistent with pure 11-cis pigment composition. However, in mice lacking the cellular retinaldehyde binding protein (CRALBP), cone spectral sensitivity contained a substantial 9-cis component. Thus, the retina visual cycle provides cones exclusively with 11-cis chromophore and this process is mediated by the 11 cis selective CRALBP in Muller cells. Finally, despite sharing the same pigment, salamander blue cones, but not green rods, recovered their sensitivity in the isolated retina. Exogenous 9-cis retinol produced robust sensitivity recovery in bleached red and blue cones but not in red and green rods, suggesting that cis retinol oxidation restricts access to the retina visual cycle to cones. PMID- 27385536 TI - Mitochondria in aging cell differentiation. PMID- 27385537 TI - A molecular dynamics study of the effect of glycosidic linkage type in the hemicellulose backbone on the molecular chain flexibility. AB - The macromolecular conformation of the constituent polysaccharides in lignocellulosic biomass influences their supramolecular interactions, and therefore their function in plants and their performance in technical products. The flexibility of glycosidic linkages from the backbone of hemicelluloses was studied by evaluating the conformational freedom of the phi and psi dihedral angles using molecular dynamic simulations, additionally selected molecules were correlated with experimental data by nuclear magnetic resonance spectroscopy. Three types of beta-(1->4) glycosidic linkages involving the monosaccharides (Glcp, Xylp and Manp) present in the backbone of hemicelluloses were defined. Different di- and tetrasaccharides with combinations of such sugar monomers from hemicelluloses were simulated, and free energy maps of the phi - psi space and hydrogen-bonding patterns were obtained. The glycosidic linkage between Glc-Glc or Glc-Man (C-type) was the stiffest with mainly one probable conformation; the linkage from Man-Man or Man-Glc (M-type) was similar but with an increased probability for an alternative conformation making it more flexible, and the linkage between two Xyl-units (X-type) was the most flexible with two almost equally populated conformations. Glycosidic linkages of the same type showed essentially the same conformational space in both disaccharides and in the central region of tetrasaccharides. Different probabilities of glycosidic linkage conformations in the backbone of hemicelluloses can be directly estimated from the free energy maps, which to a large degree affect the overall macromolecular conformations of these polymers. The information gained contributes to an increased understanding of the function of hemicelluloses both in the cell wall and in technical products. PMID- 27385539 TI - Tetramer spin singlet instability in the fluorine-substituted pyrochlore superconducting system Cd2Re2O7-x F x. AB - We synthesized polycrystalline samples of the fluorine-substituted pyrochlore rhenates Cd2Re2O7-x F x , and investigated their magnetic, transport and structural properties. The transition temperature T s1, where each Re4 tetrahedron in the Re pyrochlore network alternately expands and contracts, decreases with increasing x from 200 K at x = 0 to 100 K at x = 0.5. The strong x dependence of the magnetic and transport properties at the low temperature phase indicates that the driving force of structural phase transition is fluctuations of the tetramer spin singlet formation in order to release the spin frustration in the pyrochlore lattice. Furthermore, we found unconventional superconducting properties in Cd2Re2O7-x F x . It was found that the superconducting phase transition temperature T c markedly decreases with increasing x, suggesting that the addition of imperfection suppresses a condensation of Cooper-pair. In addition, the estimated upper critical field at zero temperature exceeds the Pauli paramagnetic limit and increases with increasing x in spite of the reduction of T c. Hence, Cd2Re2O7-x F x is suggested to be an exotic superconductor realized in the itinerant electron systems on a spin frustrated lattice. PMID- 27385538 TI - A candidate gene study identifies a haplotype of CD2 as novel susceptibility factor for systemic sclerosis. AB - OBJECTIVES: Systemic sclerosis (SSc) is a rare autoimmune disease (AID) with a complex genetic etiology. Evidence for a shared pathogenesis across AIDs is given by the well-known pleiotropism of autoimmune genes. Recently, several unbiased approaches have identified an association between polymorphisms of the CD2 gene, and rheumatoid arthritis (RA) susceptibility. The objective of this study was to investigate whether CD2 polymorphisms are associated with SSc. METHODS: Two SNPs of CD2, rs624988 and rs798036, were genotyped in a total of 1,786 SSc patients and 2,360 healthy individuals from two European populations (France and Italy). Meta-analyses were performed to assess whether an association exists between CD2 polymorphisms or haplotypes and SSc or its main subtypes. RESULTS: The combined analyses revealed an association between the rs624988 A allele and SSc susceptibility: padj=0.023, OR=1.14 (95%CI 1.04-1.25). Single marker analysis did not reveal any association between rs798036 and SSc. Haplotype analysis identified that the A-T haplotype, previously described in RA, was associated with higher susceptibility for SSc (padj=0.029, OR=1.14, 95%CI 1.04-1.25) and with the positive anti-centromere antibody sub-group of SSc patients (padj=0.009, OR=1.19 95%CI 1.07-1.32). Genotype-mRNA expression correlations revealed that the CD2 risk haplotype was associated with decreased CD2 mRNA expression in SSc patients. CONCLUSIONS: Our study establishes CD2 as a new susceptibility factor for SSc, in a European Caucasian population, confirming the sharing of autoimmune risk factors by SSc and RA. PMID- 27385540 TI - Supporting Caregivers of Children With Acute Lymphoblastic Leukemia via a Smartphone App: A Pilot Study of Usability and Effectiveness. AB - Smartphone applications are widely used for self-help interventions in adult cancer survivors. However, applications for parents of pediatric cancer patients are limited. We developed an applications to assist parents of children with acute lymphoblastic leukemia. The aim of this study is to evaluate the app's usability and effectiveness in a preliminary way. A stepwise approach and mixed methods were used. The application was initially tested by healthcare providers, and their comments and suggestions were used to develop an updated version. This version was tested by parents of children with acute lymphoblastic leukemia. Comments and nonverbal expressions of parents were recorded during a 2-week pilot test. The qualitative study was followed by a quantitative study using audit log data from the administration portal to understand how parents use the application. Six healthcare providers and 15 parents participated. Parents gained a greater knowledge of leukemia, confidence in caregiving, social support, and information on how to reduce stress. Over usability was rated as stable, useful, simple, and self-explanatory. No software failure occurred. Applications have the potential to support caregivers of pediatric cancer patients. We plan to address limitations and perform an empirical interventional study to examine its clinical effectiveness. PMID- 27385541 TI - Homeostasis Model Assessment-Adiponectin: the role of different types of physical exercise in obese adolescents. AB - BACKGROUND: Homeostasis Model Assessment-Adiponectin (HOMA-AD) is suggesting a new biomarker of insulin resistance in obese population. In this way, the purpose of this study was to investigate the effects of different kinds of exercise in the sensitive index predictor of insulin resistance. METHODS: A total of 148 obese adolescents were enrolled in the program. They aged 15-19 y, with Body Mass Index (BMI) >=P95th and were submitted to 1 year of interdisciplinary weight loss therapy, randomized in two groups, aerobic training (AT) (N.=51) and aerobic plus resistance training (N.=97). Blood samples were collected to analyze adiponectin, glucose and insulin concentrations. The insulin resistance was measured by HOMA AD and Homeostasis Model Assessment Insulin Resistance Index (HOMA-IR). RESULTS: Both kinds of exercise training promoted a decrease in body mass, body mass index, fat mass, visceral and subcutaneous fat. However, only aerobic plus resistance training was effective to reduce HOMA-AD, insulin and glucose concentration; and increase insulin sensibility and adiponectin concentration. CONCLUSIONS: The aerobic plus resistance training was more effective than AT alone to improve the HOMA-AD, suggesting clinical application on obesity, diabetes, atherosclerosis and metabolic syndrome control in the pediatric population. PMID- 27385542 TI - Level of functional capacities following soccer-specific warm-up methods among elite collegiate soccer players. AB - BACKGROUND: Different methods of warm-up may have implications in improving various aspects of soccer performance. The present study aimed to investigate acute effects of soccer specific warm-up protocols on functional performance tests. METHODS: This study using randomized within-subject design, investigated the performance of 22 collegiate elite soccer player following soccer specific warm-ups using dynamic stretching, static stretching, and FIFA 11+ program. Post warm-up examinations consisted: 1) Illinois Agility Test; 2) vertical jump; 3) 30 meter sprint; 4) consecutive turns; 5) flexibility of knee. RESULTS: Vertical jump performance was significantly lower following static stretching, as compared to dynamic stretching (P=0.005). Sprint performance declined significantly following static stretching as compared to FIFA 11+ (P=0.023). Agility time was significantly faster following dynamic stretching as compared to FIFA 11+ (P=0.001) and static stretching (P=0.001). Knee flexibility scores were significantly improved following the static stretching as compared to dynamic stretching (P=016). No significant difference was observed for consecutive turns between three warm-up protocol. CONCLUSIONS: The present finding showed that a soccer specific warm-up protocol relied on dynamic stretching is preferable in enhancing performance as compared to protocols relying on static stretches and FIFA 11+ program. Investigators suggest that while different soccer specific warm up protocols have varied types of effects on performance, acute effects of dynamic stretching on performance in elite soccer players are assured, however application of static stretching in reducing muscle stiffness is demonstrated. PMID- 27385543 TI - Body composition changes in an endurance athlete using two different training strategies. AB - Swimming, running and cycling are among the most popular and fastest growing sports in the world. Inherent in these sports is a desire to favorably alter body composition. Here we report a ~5.4 kg and ~5.3 kg fat tissue mass (FTM) loss in two separate interventions (12-16 weeks), in the same athlete, separated by 5 years. Whole body composition was assessed using dual X-ray absorptiometry (DXA). Dietary analysis for intervention 2 was completed using Mc Cance and Widdowson's composition of foods. In 2010, the male athlete (23 years, weight 85 kg, height 195 cm, 18.1% body fat) had a reduction of ~5.4 kg of FTM (15.4 vs. 10.0 kg) and an increase of ~5.1 kg of lean tissue mass (LTM) following 16 weeks of moderate intensity running (213+/-53 min/week) and circuit training (64+/-46 min/week). In 2015, the same athlete (28 years, 90.6 kg, 195 cm; 18.2%) had a ~5.3 kg loss of FTM and a ~0.8 kg increase in LTM after 12 weeks, predominately (75%) non-weight bearing exercise (49% cycling, 215+/-88 min/week; 25% running 110+/-47 min/week; 19% swimming, 83+/-27 min/week; 7% rowing machine, 29+/-26 min/week). Weekday and weekend dietary intake during intervention 2 were estimated as 2560 kcal and 3240 kcal per day, respectively. This report provides support for the hypothesis that an extended period of energy deficit is required to reduce body fat levels in amateur athletes independent of the mode of exercise. PMID- 27385545 TI - Exploring the biomechanical load of a sliding on the skin: understanding the acute skin injury mechanism of player-surface interaction. AB - BACKGROUND: Currently, there is a shortage of biomechanical data regarding acute skin injury mechanisms that are involved in player-surface contact in soccer on artificial turf. It is hypothesized that peak loads on the skin during the landing phase are an important factor in causing an acute skin injury. METHODS: Simultaneously, video analysis and load measurements using an in-ground force plate of the landing phase of a sliding tackle were recorded and correlated with observed clinical skin lesions. RESULTS: Video analysis revealed two sliding techniques: a horizontal jump and a sliding-in technique. The first technique resulted in both significantly higher vertical and horizontal peak forces during impact on the knee (2.3+/-0.4 kN and 1.4+/-0.5 kN) and thigh (4.9+/-0.9 kN and 1.8+/-0.5 kN). In combination with the observed skin lesion areas, a combined normal-shear stress of at least 24 and 14 N.cm-2 induce abrasion injuries on dry artificial turf. CONCLUSIONS: The findings of this study confirm that high peak stresses during the landing phase of a sliding is critical for inducing skin injuries on the knee and thigh. Reducing these peak shear stresses could be an important first step towards preventive measures. PMID- 27385544 TI - Circuit resistance training in women with normal weight obesity syndrome: body composition, cardiometabolic and echocardiographic parameters, and cardiovascular and skeletal muscle fitness. AB - BACKGROUND: Normal weight obesity (NWO) syndrome has been characterized in subjects with normal Body Mass Index (BMI) and high body fat mass percentage (BF%>30 for women) being a risk factor for cardiometabolic dysregulation and cardiovascular mortality. This study evaluated whether circuit resistance training (CRT) improves body composition, heart size and function, cardiometabolic parameters, and cardiorespiratory, cardiovascular and skeletal muscle fitness in women with NWO. METHODS: Data are means (95% Confidence Interval). Twenty-three women participated: 10 NWO-CRT (baseline: BMI=22.4 [21.4 23.3] kg/m2; BF%=44.5 [41.0-48.0]%) performed CRT; and 13 untrained NWO-control (baseline: BMI=21.7 [20.8-22.7] kg/m2; BF%=37.8 [34.6-41.1]%). At baseline and after 10 weeks were performed/measured dual-energy X-ray absorptiometry, echocardiography, blood tests, arterial pressure, exercise testing, and total overload-by-training-session (TOL). RESULTS: At baseline, the NWO-CRT exhibited larger BF (27.28 [23.9-30.6] kg) than NWO-control (22.41 [19.5-25.3] kg) (P=0.0227). After training, NWO-CRT: reduced 8 kg of BF (P=0.000002); became BF% lower than NWO-control (33.1 [30.1-36.0] <37.0 [34.3-39.6]%, P=0.0423), with 30% of NWO-CRT subjects becoming without-obesity; reduced 3 kg in trunk fat mass (P=0.000005); showed fasting glucose (72.8 [69.4-76.2] mg/dL) smaller than NWO control (81.7 [78.6-84.8] mg/dL) (P=0.004); increased TOL (5087.5 [4142.5-6032.5] to 6963.3 [6226.4-7700.2] rep.kg, P=0.0004); increased load at VO2peak (122.5 [106.8-138.2] to 137.5 [118.18-156.82] W, P=0.0051); reduced double product/load at VO2peak ratio (277.4 [222.1-332.8] to 237.7 [194.2-281.2] mmHg.bpm/W, P=0.0015); and increased left ventricular mass/body surface area ratio (84.29 [78.98-89.6] to 90.29 [81.45-99.12] g/m2, P=0.0215). CONCLUSIONS: CRT reduced BF% and generated cardiometabolic, cardiac, skeletal muscle and cardiovascular benefits, being a useful strategy to combat the normal weight obesity syndrome in women. PMID- 27385546 TI - Physical performance and positional differences among young female volleyball players. AB - BACKGROUND: The purpose of this study was to investigate the association among anthropometric, physical performance parameters, and dynamic postural control attributes of young female volleyball athletes, and to determine if differences exist in these attributes according to playing position. METHODS: Forty-three young female volleyball players participated in this study. Players were divided by position into hitters (N.=17), middle blockers (N.=8), setters (N.=10), and liberos (N.=8). Stature, body mass, vertical jump (VJ), peak power, horizontal jump (HJ), sit-and-reach (SRT), star excursion balance (SEBT), and agility (e.g. shuttle run and Illinois agility test) tests were assessed on non-consecutive days in randomized order. RESULTS: No difference was found between groups for SRT, peak power, VJ, and HJ (P<=0.05). Middle blockers and hitters were taller than setters (P<=0.05). Middle blockers were also taller than liberos (P=0.017). Significant differences were observed among groups for agility tests, with hitters significantly faster than setters (P=0.023) and middle blockers (P=0.037). In addition, liberos were significantly faster than setters (P=0.032) and middle blockers (P=0.046), during the Illinois agility test. No difference was observed between groups for reach distance scores in the SEBT. CONCLUSIONS: These results demonstrate important positional differences in agility measures of young female volleyball players. Coaches can use this information to determine the type of physical profile that is needed for specific positions and to design training programs to maximize strength, power, and neuromuscular development of young female volleyball athletes. PMID- 27385547 TI - Effect of exercise in air-conditioned and non-air-conditioned environment in cardiac autonomic control. PMID- 27385548 TI - Predicting race time in male amateur marathon runners. AB - BACKGROUND: The aim of the study was to analyze the relationship between anthropometry, training characteristics, muscular strength and effort-related cardiovascular response and marathon race time in male amateur runners. METHODS: A total of 84 male amateur marathon runners aged between 23 and 70 years took part in this study (41.0+/-9.5 years). All of them competed in the 2013 edition of the Madrid Marathon with a finish time between 169.8 and 316 minutes (226.0+/ 28.5 minutes). Age, running experience, number of marathon races finished, mean kilometers run weekly in the last three months, and previous personal best time in the 10 km, half marathon and marathon were recorded. Moreover, anthropometric characteristics, and the results from the Ruffier Test and a whole-body isometric force test were measured. After the marathon, the race time was registered. RESULTS: Training volume (r=-0.479; P=0.001), previous running milestones (marathon r=0.756; half-marathon r=0.812; 10-km r=0.732; P<0.001), cardiovascular fitness (r=0.371; P=0.001) and anthropometric variables (body mass, Body Mass Index, body fat percentage, skinfolds and lower leg volume) were correlated to marathon performance (P<0.05). Two regression models appeared from the data with r2>0.50. The best, including body fat percentage, heart rate change during the recovery after the Ruffier Test and the half-marathon race time, was strongly correlated with real marathon performance (r=0.77; P<0.001). A second regression model was proposed replacing the half-marathon performance with the 10-km race time, reducing the correlation to 0.73 (P<0.001). CONCLUSIONS: Marathon performance could be partially predicted by two different equations, including body fat percentage, recovery heart rate in the Ruffier Test and a half-marathon or 10-km performance. PMID- 27385549 TI - Effects of exercise training experience on hand grip strength, body composition and postural stability in fitness pole dancers. AB - BACKGROUND: Although the growing popularity of pole dance as a leisure-time activity of people of all ages, the problem of physical effects of exercise on the pole is not considered in the scientific literature. The aim of this study was to evaluate and compare the hand grip strength, body composition and postural stability of fitness pole dancers with different training experience. METHODS: The inclusion criteria for this study were met by 52 female pole dancers. The research program included assessment of body composition (using BC-418 Segmental Body Composition Analyzer, Tanita, Tokyo, Japan), hand grip strength by hydraulic dynamometer JAMAR, and postural stability using ALFA stabilometric platform. RESULTS: Significant differences depending on the pole dance advancement level were found in postural stability and hand-grip strength. The average values of the surface area and the length sway indicated by feet center of pressure were significantly decreasing with the increasing group experience (P<0.05). Strength level was increasing with the consecutive advancement level (right hand chi2=9.595, P=0.008, left hand chi2=8.936, P=0.011). CONCLUSIONS: Regular practice of pole dance fitness can contribute to a significant increase of strength and improvement of the postural stability, which is important for the entire musculoskeletal system. However, further studies on the beneficial and negative (e.g. injuries) impact of exercises on the pole on the musculoskeletal system are required, including larger group of respondents, their diverse age and, above all, longitudinal studies. PMID- 27385550 TI - Versatile Room-Temperature-Phosphorescent Materials Prepared from N-Substituted Naphthalimides: Emission Enhancement and Chemical Conjugation. AB - Purely organic materials with room-temperature phosphorescence (RTP) are currently under intense investigation because of their potential applications in sensing, imaging, and displaying. Inspired by certain organometallic systems, where ligand-localized phosphorescence ((3) pi-pi*) is mediated by ligand-to metal or metal-to-ligand charge transfer (CT) states, we now show that donor-to acceptor CT states from the same organic molecule can also mediate pi-localized RTP. In the model system of N-substituted naphthalimides (NNIs), the relatively large energy gap between the NNI-localized (1) pi-pi* and (3) pi-pi* states of the aromatic ring can be bridged by intramolecular CT states when the NNI is chemically modified with an electron donor. These NNI-based RTP materials can be easily conjugated to both synthetic and natural macromolecules, which can be used for RTP microscopy. PMID- 27385552 TI - Detection of Retinal Hemangioblastomas in von Hippel-Lindau Disease Using Three Dimensional Arterial Spin Labeling MR Imaging at 3T. PMID- 27385554 TI - Correction to Structural Investigation of B-Raf Paradox Breaker and Inducer Inhibitors. PMID- 27385553 TI - Image Non-Uniformity Correction for 3-T Gd-EOB-DTPA-Enhanced MR Imaging of the Liver. AB - PURPOSE: Image non-uniformity may cause substantial problems in magnetic resonance (MR) imaging especially when a 3-T scanner is used. We evaluated the effect of image non-uniformity correction in gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MR imaging using a 3-T scanner. METHODS: Two commercially available methods for image non-uniformity correction, surface coil intensity correction (SCIC), and phased-array uniformity enhancement (PURE), were applied to Gd-EOB-DTPA-enhanced images acquired at 3-T in 20 patients. The calibration images were used for PURE and not for SCIC. Uniformity in the liver signal was evaluated visually and using histogram analysis. The liver-to-muscle signal ratio (LMR) and liver-to-spleen signal ratio (LSR) were estimated, and the contrast enhancement ratio (CER) was calculated from the liver signal, LMR, and LSR. RESULTS: Without non-uniformity correction, hyperintensity was consistently observed near the liver surface. Both SCIC and PURE improved uniformity in the liver signal; however, the superficial hyperintensity remained after the application of SCIC, especially in the hepatobiliary-phase images, and focal hyperintensity was shown in the lateral segment of the left hepatic lobe after the application of PURE. PURE increased LMR dramatically and LSR mildly, with no changes in CERs. SCIC depressed temporal changes in LMR and LSR and obscured contrast effects, regardless of the method used for calculation of CER. CONCLUSION: SCIC improves uniformity in the liver signal; however, it is not suitable for a quantitative assessment of contrast effects. PURE is indicated to be a useful method for non-uniformity correction in Gd-EOB-DTPA-enhanced MR imaging using a 3-T scanner. PMID- 27385555 TI - Recent Advances in the Synthesis of Azonia Aromatic Heterocycles. AB - Azonia aromatic heterocycles are an important subclass of aza-heterocyles as they are the structural motif of relevant cationic alkaloids, and they have a wide range of potential applications such as bioactive compounds and organic materials. In this Synopsis, recent and novel approaches to their synthesis are surveyed, with particular emphasis on ring-closing metathesis reactions and annulation reactions based on C-H activation. PMID- 27385551 TI - Systems view of adipogenesis via novel omics-driven and tissue-specific activity scoring of network functional modules. AB - The investigation of the complex processes involved in cellular differentiation must be based on unbiased, high throughput data processing methods to identify relevant biological pathways. A number of bioinformatics tools are available that can generate lists of pathways ranked by statistical significance (i.e. by p value), while ideally it would be desirable to functionally score the pathways relative to each other or to other interacting parts of the system or process. We describe a new computational method (Network Activity Score Finder - NASFinder) to identify tissue-specific, omics-determined sub-networks and the connections with their upstream regulator receptors to obtain a systems view of the differentiation of human adipocytes. Adipogenesis of human SBGS pre-adipocyte cells in vitro was monitored with a transcriptomic data set comprising six time points (0, 6, 48, 96, 192, 384 hours). To elucidate the mechanisms of adipogenesis, NASFinder was used to perform time-point analysis by comparing each time point against the control (0 h) and time-lapse analysis by comparing each time point with the previous one. NASFinder identified the coordinated activity of seemingly unrelated processes between each comparison, providing the first systems view of adipogenesis in culture. NASFinder has been implemented into a web-based, freely available resource associated with novel, easy to read visualization of omics data sets and network modules. PMID- 27385556 TI - Platelet abnormalities in a family with von Willebrand disease type 2B (V1316M) and association with bleeding score. PMID- 27385557 TI - The Physician-as-Stakeholder: An Exploratory Qualitative Analysis of Physicians' Motivations for Using Shared Decision Making in the Emergency Department. AB - BACKGROUND: Shared decision making (SDM) is increasingly recognized as an important facet of patient-centered care. Despite growing interest in SDM in the emergency department (ED), little is known about emergency physicians' (EPs') motivations for using SDM. Understanding current patterns of SDM use and EP's rationale for using SDM is essential for the development of interventions to increase use. OBJECTIVES: Recognizing the EP as an important stakeholder in SDM research, we sought to identify and explore factors that may motivate EPs' engagement in SDM. METHODS: In this qualitative study, informed by the Theory of Planned Behavior and Social Cognitive Theory, we conducted semistructured interviews with a purposeful sample of EPs. Interviews were recorded and transcribed verbatim. Using a directed qualitative content analysis approach, three members of the research team performed open coding of the transcripts in an iterative process, building a provisional code book as coding progressed. Respondent validation was employed to ensure methodologic rigor. RESULTS: Fifteen EPs, ages 31-65, from both academic and community practice settings, were interviewed. Several had not heard of the specific phrase "shared decision making," but all understood the concept and felt that they used SDM techniques to some degree. Most noted they had often had an agenda when they used SDM, which often motivated them to have the conversation. Agendas described included counteracting an algorithmic or defensive approach to diagnosis and treatment, avoiding harmful tests, or sharing uncertainty. All participants believed that patients benefited from SDM in terms of satisfaction, engagement, or education. Nearly all participants identified research outcomes that they felt would encourage their use of SDM (e.g., improvements in patient engagement, mitigation of risk) and many prioritized patient-centered outcomes over systems outcomes such as improved resource utilization. Little consensus was seen, however, regarding the importance of individual outcomes: of eight potential research outcomes participants endorsed, no single outcome was endorsed by even half of the physicians interviewed. CONCLUSION: Emergency physicians identified many factors that motivated them to use SDM. This study informs current research on SDM in the ED, particularly regarding the motivations of the physician-as stakeholder. PMID- 27385558 TI - Effect of thermal processing on the profile of bioactive compounds and antioxidant capacity of fermented orange juice. AB - Previously, we reported that alcoholic fermentation enhanced flavanones and carotenoids content of orange juice. The aim of this work was to evaluate the influence of pasteurization on the qualitative and quantitative profile of bioactive compounds and the antioxidant capacity of fermented orange juice. Ascorbic acid (203 mg/L), total flavanones (647 mg/L), total carotenoids (7.07 mg/L) and provitamin A (90.06 RAEs/L) values of pasteurized orange beverage were lower than those of fermented juice. Total phenolic remained unchanged (585 mg/L) and was similar to that of original juice. The flavanones naringenin-7-O glucoside, naringenin-7-O-rutinoside, hesperetin-7-O-rutinoside, hesperetin-7-O glucoside and isosakuranetin-7-O-rutinoside, and the carotenoids karpoxanthin and isomer, neochrome, lutein, zeta-carotene, zeaxanthin, mutatoxanthin epimers, beta cryptoxanthin and auroxanthin epimers were the major compounds. Pasteurization produced a decrease in antioxidant capacity of fermented juice. However, TEAC (5.45 mM) and ORAC (6353 MUM) values of orange beverage were similar to those of original orange juice. The novel orange beverage could be a valuable source of bioactive compounds with antioxidant capacity and exert potential beneficial effects. PMID- 27385559 TI - Synthesis of thiolate-protected Au nanoparticles revisited: U-shape trend between the size of nanoparticles and thiol-to-Au ratio. AB - We report a new understanding of the factors controlling the size of thiolate protected gold nanoparticles (Au NPs): the formation and the state of a protecting layer (Au(i)-thiolate motifs) outside the gold core determine the size of Au NPs, depending on the feeding thiol-to-Au ratio. As a result, a U-shape trend is identified between the size of Au NPs and the thiol-to-Au ratio as opposed to the commonly expected decreasing trend. PMID- 27385560 TI - Effects of four-month handbike training under free-living conditions on physical fitness and health in wheelchair users. AB - PURPOSE: Recognizing the encouraging effect of challenging events, the HandbikeBattle (HBB) was created to promote exercise among wheelchair users. The purpose of this study was to reveal the effects on physical fitness and health outcomes of four-month handbike training under free-living conditions in preparation for the event. METHODS: In this prospective cohort study, 59 relatively inexperienced handyclists participated in the HBB of 2013 or 2014. Incremental exercise tests were conducted, respiratory function was tested and anthropometrics were measured before and after the preparation period. Main outcome measures were peak power output (POpeak), peak oxygen uptake (VO2peak) and waist circumference, of which the changes were tested using repeated measures ANOVA. To detect possible determinants of changes in physical fitness, a linear regression analysis was conducted with personal characteristics, executed training volume and upper-extremity complaints during the training period as independent variables. RESULTS: POpeak, VO2peak and waist circumference improved significantly with 17%, 7% and 4.1%, respectively. None of the included variables were significant determinants for the changes in POpeak found as a result of the training. CONCLUSION: A challenging event such as the HBB provokes training regimes among participants of sufficient load to realize substantial improvements in physical fitness and health outcomes. Implications for Rehabilitation Due to the often impaired muscle function in the lower-limbs and an inactive lifestyle, wheelchair users generally show considerably lower levels of fitness compared to able-bodied individuals. This prospective cohort study showed that four months of handbike training under free-living conditions in preparation for this event resulted in substantial improvements in physical fitness and health outcomes in wheelchair users. The creation of a challenging event such as the HandbikeBattle as part of a follow-up rehabilitation practice can therefore be a useful tool to help wheelchair users initiate or keep training to improve their physical fitness and health. PMID- 27385562 TI - The Rosen-Cunningham debate: another, alternative view. PMID- 27385561 TI - Joint eigenvector estimation from mutually anisotropic tensors improves susceptibility tensor imaging of the brain, kidney, and heart. AB - PURPOSE: To develop a susceptibility-based MRI technique for probing microstructure and fiber architecture of magnetically anisotropic tissues-such as central nervous system white matter, renal tubules, and myocardial fibers-in three dimensions using susceptibility tensor imaging (STI) tools. THEORY AND METHODS: STI can probe tissue microstructure, but is limited by reconstruction artifacts because of absent phase information outside the tissue and noise. STI accuracy may be improved by estimating a joint eigenvector from mutually anisotropic susceptibility and relaxation tensors. Gradient-recalled echo image data were simulated using a numerical phantom and acquired from the ex vivo mouse brain, kidney, and heart. Susceptibility tensor data were reconstructed using STI, regularized STI, and the proposed algorithm of mutually anisotropic and joint eigenvector STI (MAJESTI). Fiber map and tractography results from each technique were compared with diffusion tensor data. RESULTS: MAJESTI reduced the estimated susceptibility tensor orientation error by 30% in the phantom, 36% in brain white matter, 40% in the inner medulla of the kidney, and 45% in myocardium. This improved the continuity and consistency of susceptibility-based fiber tractography in each tissue. CONCLUSION: MAJESTI estimation of the susceptibility tensors yields lower orientation errors for susceptibility-based fiber mapping and tractography in the intact brain, kidney, and heart. Magn Reson Med 77:2331-2346, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27385563 TI - Surface-Enhanced Raman Scattering Active Plasmonic Nanoparticles with Ultrasmall Interior Nanogap for Multiplex Quantitative Detection and Cancer Cell Imaging. AB - Due to its large enhancement effect, nanostructure-based surface-enhanced Raman scattering (SERS) technology had been widely applied for bioanalysis and cell imaging. However, most SERS nanostructures suffer from poor signal reproducibility, which hinders the application of SERS nanostructures in quantitative detection. We report an etching-assisted approach to synthesize SERS active plasmonic nanoparticles with 1 nm interior nanogap for multiplex quantitative detection and cancer cell imaging. Raman dyes and methoxy poly(ethylene glycol) thiol (mPEG-SH) were attached to gold nanoparticles (AuNPs) to prepare gold cores. Next, Ag atoms were deposited on gold cores in the presence of Pluronic F127 to form a Ag shell. HAuCl4 was used to etch the Ag shell and form an interior nanogap in Au@AgAuNPs, leading to increased Raman intensity of dyes. SERS intensity distribution of Au@AgAuNPs was found to be more uniform than that of aggregated AuNPs. Finally, Au@AgAuNPs were used for multiplex quantitative detection and cancer cell imaging. With the advantages of simple and rapid preparation of Au@AgAuNPs with highly uniform, stable, and reproducible Raman intensity, the method reported here will widen the applications of SERS-active nanoparticles in diagnostics and imaging. PMID- 27385564 TI - CD4+ T cell-dominant insulitis in acute-onset Type 1 diabetes mellitus associated with intraductal papillary mucinous adenoma. AB - The loss of insulin-producing pancreatic beta-cells in Type 1 diabetes mellitus (DM) is presumably the result of a T cell-mediated process. In general, CD8+ T cells are the predominant lymphocytes in the insulitis lesions, and CD4+ T cell dominant insulitis is very rare. We present a case of a 72-year-old woman presented with excessive thirst and a 3-month history of weight loss. She was in a state of ketosis, and her plasma glucose concentration and HbA1c value were elevated. Moreover, anti-islet autoantibodies were positive, thus acute-onset Type 1 DM was diagnosed. At the time of diagnosis, a tumour was detected in the pancreas; total pancreatectomy was carried out 2 months later. The pathological diagnosis was intraductal papillary mucinous adenoma. Immunohistochemical staining of a sample of non-tumorous pancreatic tissue revealed 13 insulitis lesions infiltrated by both CD4+ and CD8+ T cells, and interestingly there were more CD4+ T cells than CD8+ T cells in the lesions. Moreover, B cells and macrophages had also infiltrated the lesions, and these two cell frequencies were both positively correlated with CD4+ as well as CD8+ T cell frequencies. This was a rare case with acute-onset Type 1 DM characterized by CD4+ T cell-dominant insulitis. Proinflammatory cytokines that can promote beta-cell apoptosis or CD8+ T cell function are reported to be secreted from CD4+ T cells. Thus, together with B cells and macrophages, CD4+ T cell-associated immune responses may have, directly and/or indirectly, played a role in the pathogenesis of the Type 1 DM in this patient. PMID- 27385565 TI - Insight into the CH3NH3PbI3/C interface in hole-conductor-free mesoscopic perovskite solar cells. AB - Perovskite solar cells (PSCs) with hole-conductor-free mesoscopic architecture have shown superb stability and great potential in practical application. The printable carbon counter electrodes take full responsibility of extracting holes from the active CH3NH3PbI3 absorbers. However, an in depth study of the CH3NH3PbI3/C interface properties, such as the structural formation process and the effect of interfacial conditions on hole extraction, is still lacking. Herein, we present, for the first time, an insight into the spatial confinement induced CH3NH3PbI3/C interface formation by in situ photoluminescence observations during the crystallization process of CH3NH3PbI3. The derived reaction kinetics allows a quantitative description of the perovskite formation process. In addition, we found that the interfacial contact between carbon and perovskite was dominant for hole extraction efficiency and associated with the photovoltaic parameter of short circuit current density (JSC). Consequently, we conducted a solvent vapor assisted process of PbI2 diffusion to carefully control the CH3NH3PbI3/C interface with less unreacted PbI2 barrier. The improvement of interface conditions thereby contributes to a high hole extraction proved by the charge extraction resistance and PL lifetime change, resulting in the increased JSC valve. PMID- 27385566 TI - Existence of Two Kinds of Sulfur-reducing Systems in Iron-oxidizing Bacterium Thiobacillus ferrooxidans. AB - Intact cells of Thiobacillus ferrooxidans NASF-1 incubated under anaerobic conditions in a reaction mixture containing 0.5% colloidal sulfur produced hydrogen sulfide (H2S) extracellularly. The amount of H2S produced by cells increased corresponding to the cell amounts and colloidal sulfur. Two activity peaks of H2S production were observed at pH 1.5 and 7.5. We tentatively called the enzyme activities pH 1.5- and pH 7.5-sulfur reducing systems, respectively. Seven strains of T. ferrooxidans tested had both the activities of pH 1.5- and pH 7.5-sulfur reducing systems, but at different levels. T. ferrooxidans NASF-1 showed the highest activity of the pH 1.5-sulfur reducing system and strain 13598 from ATCC showed the highest activity of the pH 7.5-sulfur reducing system. Further characteristics of H2S production were studied with intact cells of NASF 1. The optimum temperatures for pH 1.5- and pH 7.5-sulfur reducing systems of NASF-1 were 40 degrees C. Hydrogen sulfide production continued for 8 days and total amounts of H2S produced at pH 7.5 and 1.5 were 832 and 620 nmol/mg protein, respectively. The pH 7.5-sulfur reducing system used only colloidal sulfur as the electron acceptor. However, the pH 1.5-sulfur reducing system used both colloidal sulfur and tetrathionate. Thiosulfate, dithionate, and sulfite could not be used as the electron acceptor for both of the sulfur reducing systems. Potassium cyanide activated by 3- fold the pH 1.5-sulfur reducing system activity at 0.5 mM but did not affect the activity of the pH 7.5-sulfur reducing system. An inhibitor of sulfite reductase, p-chloromercuribenzene sulfonic acid, did not affect either enzyme activity. Sodium molybdate and monoiodoacetic acid strongly inhibited the activity of the pH 1.5-sulfur reducing system at 1.0 mM, but not the activity of pH 7.5-sulfur reducing system. PMID- 27385567 TI - Structure-activity Relationship for the Insect Antifeedant Activity of Benzofuran Derivatives. AB - Coumaran (2,3-dihydrobenzofuran), a secondary metabolite of Cyperus nipponicus, inhibits the feeding of polyphagous insects. This secondary metabolite is regarded as one of the defensive systems of the Cyperaceae. A number of naturally occurring benzofurans that differ in their substitution pattern and oxidation state have been investigated for their ability to inhibit insect feeding by a bioassay with the common cutworm (Spodoptera litura F. Noctuidae) that applies the leaf disk method. The evaluation of the antifeedant activity of each test compound used the ED50 value based on the dose-response curve that was calculated with the probit method. The 2,3-dihydrobenzofuran derivative, 7-acetyl-4,6 dimethoxy-2-isopropenyl-2,3-dihydrobenzofuran, had an ED50 value of 1.3 MUg (5.4*10(-9) mol)/cm(2) against the common cutworm. The introduction of methoxy and acetyl groups increased the insect antifeedant activity. Furthermore, the insect antifeedant activity increased with decreasing lipophilicity of the test compounds. PMID- 27385568 TI - Formation Mechanism for Potent Antioxidative o-Dihydroxyisoflavones in Soybeans Fermented with Aspergillus saitoi. AB - The formation mechanism for the potent antioxidative o-dihydroxyisoflavones, 8 hydroxydaidzein (8-OHD) and 8-hydroxygenistein (8-OHG), was studied by incubating whole soybeans in a solid culture and a soybean extract in a liquid culture with Aspergillus saitoi. Analyses of changes in the isoflavone analogue content, beta glucosidase activity, and isoflavone hydroxylation ability indicated that 8-OHD and 8-OHG were formed from daidzein and genistein, respectively, by microbial hydroxylation, being respectively liberated from daidzin and genistin by beta glucosidase from A. saitoi during incubation. No selective hydroxylation reaction at the 8-position of daidzein and genistein were apparent during the vegetative stage, but were induced at the stage of sporulation. PMID- 27385569 TI - Autoxidation of Linoleic Acid Encapsulated with Polysaccharides of Differing Weight Ratio. AB - Linoleic acid was encapsulated with pullulan, maltodextrin and gum arabic at various weight ratios of the fatty acid to wall material by the hot-air-drying method. The autoxidative process of the encapsulated linoleic acids was observed at 37 degrees C and at a relative humidity of 75%. The weight ratio strongly affected the autoxidative process, autoxidation being more suppressed with smaller ratios. The autoxidation process of encapsulated linoleic acid leveled off at fraction Yinfinity of the unoxidized substrate within 15 days. The Yinfinity value strongly depended on both the ratio and the wall material, and steeply decreased near the ratio of 0.75 for every wall material. The dependence of the Yinfinity value on the weight ratio was analyzed by the two- and three dimensional models for percolation theory. The two-dimensional model expressed well the experimentally observed dependence. PMID- 27385570 TI - Production of Biodegradable Polyester by a Transgenic Tobacco. AB - The acetoacetyl-CoA reductase gene (phbB) of Ralstonia eutropha and the poly[(R) (-)-3-hydroxyalkanoate] synthase gene (phaCAC) of Aeromonas caviae were introduced into tobacco plant by Agrobacterium mediated transformation method. The resulting transgenic tobacco expressed both introduced genes and the expression of these genes was confirmed by enzymatic analysis and western blotting. GC-MS analysis of the chloroform extract of tobacco leaves indicated that the transgenic plant produced biodegradable polyester, poly-[(R)-(-)-3 hydroxybutyrate]. GPC analysis indicated that the number-average molecular weights (Mn) and polydispersity (Mw/Mn) were 32,000 and 1.90, respectively. PMID- 27385571 TI - Fatty Acids and Their Derivatives as Modulators of Appressorium Formation in Magnaporthe grisea. AB - Appressorium formation in germinating conidia of Magnaporthe grisea was inhibited on inductive and on noninductive surfaces by monounsaturated fatty acids with chain lengths of 16, 18, or 20 carbon atoms. On a noninductive surface, the inhibition was only observed upon stimulation with 1,16-hexadecanediol or oleyl alcohol, but not upon stimulation with 8-(4-chlorophenylthio)-adenosine-3',5' monophosphate. In the C18-series, fatty acids with a double bond in position 9 were the most active ones. At 1 MUg/ml of oleic or elaidic acid, less than 30% of the germinated conidia formed appressoria. The mode of inhibition was competitive to the inducing agent. On an inductive surface, compared to a noninductive surface the concentrations of oleic and elaidic acid needed for inhibition of appressorium formation were one order of magnitude higher. Methyl esters of inhibitory fatty acids and acids with two double bonds were not active. Like oleyl alcohol, elaidyl alcohol and petroselinyl alcohol stimulated infection structure formation on the noninductive surface. PMID- 27385572 TI - Four Novel Taxane Diterpenoids from the Needles of Japanese Yew, Taxus cuspidata. AB - Four novel taxane diterpenes were isolated from the needles of the Japanese yew, Taxus cuspidata. Their structures were established as 1-hydroxy taxuspine C, 2alpha,7beta,9alpha, 10beta,13alpha-pentaacetoxy-5alpha-cinnamoyloxy-4beta,20 epoxy- taxa-11-en-1beta-ol, 2alpha,9alpha,10beta,13alpha-tetraacetoxy-taxa-4(20), 11-dien-5alpha-ol and 10-deacetyl taxinine on the basis of spectral analyses. PMID- 27385573 TI - Cell Layer-Specific Accumulation of Anthocyanins in Response to Gibberellic Acid in Tepals of Hyacinthus orientalis. AB - Anthocyanin-producing cells in the tepals of flower buds of Hyacinthus orientalis were investigated. In field-grown flowers, anthocyanins were only produced in L2 cells (cells in the sub-epidermis) of tepals. However, when early-stage flower buds were cultured on medium containing GA3, anthocyanins were produced not only in L2 cells but also in L1 cells (cells in the epidermal layer) of tepals. The same anthocyanins were produced in tepals of both field-grown flowers and flower buds cultured in vitro. PMID- 27385574 TI - Isolation of an Antioxidative Substance Produced by Aspergillus repens. AB - The acidic fraction of an extract of the culture liquid of Aspergillus repens MA0197 showed strong antioxidative activity when tested by the ferric thiocyanate and TBA methods. Chromatographic purification of this acidic fraction gave an active substance identified as Neoechinulin A. This compound showed higher antioxidative activity than alpha-tocopherol and could be expected to act as an antioxidant in Katsuobushi. PMID- 27385575 TI - Reidentification of Facultatively Alkaliphilic Bacillus sp. C-125 to Bacillus halodurans. AB - Alkaliphilic Bacillus sp. C-125 was taxonomically characterized by physiological and biochemical characteristics, 16S rDNA sequence similarity, and DNA-DNA hybridization analyses. Phylogenetic analysis of strain C-125 based on comparison of 16S rDNA sequences showed that this strain is closely related to Bacillus halodurans. DNA-DNA hybridization analysis was done comparing C-125 and related Bacillus reference strains. The highest level of DNA-DNA relatedness (86%) was found between strain C-125 and B. halodurans. Our findings demonstrate that strain C-125 is a member of the species B. halodurans. PMID- 27385576 TI - A New Affinity Chromatography Using Yeast Invertase-Sepharose 4B for Purification of Plant Endo-beta-N-acetylglucosaminidases. AB - For the purification of plant endo-beta-N-acetylglucosaminidase, in this report, we introduce a new affinity chromatography using the reduced and carboxymethylated yeast invertase (cm-YI) as a ligand. Two plant endo-beta-N acetylglucosaminidases (endo-LE from tomato fruits (Kimura, Y., et al. Biochim. Biophys. Acta 1381, 27-36 (1998)) and endo-GB from Ginkgo biloba seeds (Kimura, Y., et al. Biosci. Biotechnol. Biochem., 62, 253-261 (1998)) could completely bind to the high-mannose type N-glycans linked to the immobilized yeast invertase and the activities of both enzymes could be recovered by increasing the concentration of NaCl. By using this purification procedure with some other purification procedures, endo-LE could be purified 1,700-fold and endo-GB was purified to apparent homogeneity at 63 kDa as reported previously. PMID- 27385577 TI - 16-O-Demethyl Fusicoccin J and Its 3-Epimer from Fusicoccum amygdali, and Their Seed Germination-stimulating Activity in the Presence of Abscisic Acid. AB - Our search for new metabolites biosynthetically related to fusicoccin with potent plant growth-stimulating activity from the culture filtrate of Fusicoccum amygdali F6 resulted in the isolation of a new derivative of fusicoccin J, as well as fusicoccin J and 16-O-demethyl 3-epifusicoccin J. Its structure was analyzed by 600 MHz NMR spectrometry and identified as 16-O-demethyl fusicoccin J. The biosynthetic relationships among 16-O-demethyl fusicoccin J and its 3 epimer, and fusicoccin J are discussed in connection with the co-occurrence of both of the 3-epimers of 16-O-demethyl fusicoccin J. 16-O-Demethyl fusicoccin J and its 3-epimer showed only low germination-stimulating activity toward lettuce seeds in the presence of abscisic acid (20 MUM), the latter being slightly more active than the former. PMID- 27385578 TI - Ion-transport Activity of Phenylpentanoic Acids Occurring in the Roots of Athyrium yokoscense. AB - 5-(3'-Hydroxyphenyl)pentanoic acid (1) and 5-(3'-methoxyphenyl)pentanoic acid (2) occurring in the roots of Athyrium yokoscense showed transport activity to alkaline and alkaline earth metal ions and heavy divalent metal ions. PMID- 27385579 TI - Total Synthesis of (+)-(2S,3R)-Piscidic Acid via Catalytic Asymmetric Dihydroxylation of a Trisubstituted Olefin. AB - (+)-(2S,3R)-Piscidic acid was efficiently synthesized with high optical purity (90% e.e.) via Sharpless catalytic asymmetric dihydroxylation of a trisubstituted olefin in only 6 steps from commercially available 4-hydroxyphenylpyruvic acid as the starting material. The reaction proceeded with high optical purity by using the chiral ligands, dihydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether or dihydroquinidine 1,4-anthraquinonediyl diether. PMID- 27385580 TI - Errata. AB - p. 592, right column, line 13, anti-asthmatic p. 592, right column, line 10 from the bottom, thiosulfinates p. 593, right column, line 21 and 23, and in Table 1, MUg/ml Wrong:anti-asthmatictiosulfinates mg/ml Right:anti-asthmatic thiosulfinates MUg/ml. PMID- 27385581 TI - Dy3+ -, Sm3+ -, Ce3+ - and Tb3+ -activated optical properties of microcrystalline BaMgP2 O7 phosphors. AB - Photoluminescence (PL) and thermoluminescence (TL) properties of rare earth (RE) ion (RE = Dy3+ , Sm3+ , Ce3+ , Tb3+ ) activated microcrystalline BaMgP2 O7 phosphors are presented in this work. Non-doped and doped samples of BaMgP2 O7 were prepared using a solid state diffusion method and characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), PL and TL. The XRD measurement confirmed the phase purity of the BaMgP2 O7 host matrix. The average particle size was found through SEM measurement to be around 2 MUm. All activators using the PL technique displayed characteristic excitation and emission spectra that corresponded to their typical f -> f and f -> d transitions respectively. Thermoluminescence measurements showed that BaMgP2 O7 :RE (RE = Dy3+ , Sm3+ , Tb3+ , Ce3+ ) and co-doped BaMgP2 O7 :Ce3+ ,Tb3+ phosphors have also TL behaviour. PMID- 27385582 TI - Occupational balance in health professionals in Sweden. AB - BACKGROUND: Health care employees are often women, a group that has high degrees of sick leave and perhaps problems attaining occupational balance. However, people think differently about their everyday activities and it is therefore important to take their perceptions into account but occupational balance has not yet been measured in health professionals. The aim was to describe occupational balance in three different samples of health professionals in Sweden. A further aim was to investigate whether occupational therapists (OTs) rate their occupational balance differently from other health professionals. MATERIAL AND METHOD: Four hundred and eighty-two health professionals, employees in public dentistry, mental health care and OTs, aged 21-70 years participated. The participants' occupational balance was measured using the occupational balance questionnaire (OBQ). RESULTS: The ratings of occupational balance were similar to earlier studies and did not differ significantly between the samples. The OTs' occupational balance was also similar to that of the other health professionals. CONCLUSION: The similarities in occupational balance indicate the same difficulties in attaining it. SIGNIFICANCE: The result highlights the possibility that working people face similar difficulties in achieving occupational balance. Further research is warranted about how to attain it. PMID- 27385583 TI - Controlled Synthesis of Au@AgAu Yolk-Shell Cuboctahedra with Well-Defined Facets. AB - The synthesis of Au@AgAu yolk-shell cuboctahedra nanoparticles formed by galvanic replacement in a seed-mediated method is described. Initially, single-crystal Au seeds are used for the formation of Au@Ag core-shell nanocubes, which serve as the template material for the deposition of an external Au layer. The well controlled synthesis yields the formation of cuboctahedra nanoparticles with smooth inner and outer Au/Ag surfaces. The deposition/oxidation process is described to understand the formation of cuboctahedra and octahedra nanoparticles. The Au core maintains the initial morphology of the seed and remains static at the center of the yolk-shell because of residual Ag. Structural analysis of the shell indicates intrinsic stacking faults (SFs) near the surface. Energy dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) compositional analysis show an Au-Ag nonordered alloy forming the shell. The three-dimensional structure of the nanoparticles presented open facets on the [111] as observed by electron tomography SIRT reconstruction over a stack of high angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) images. The geometrical model was validated by analyzing the direction of streaks in coherent nanobeam diffraction (NBD). The catalytic activity was evaluated using a model reaction based on the reduction of 4-nitrophenol (4-NTP) by NaBH4 in the presence of Au@AgAu yolk-shell nanoparticles. PMID- 27385584 TI - Systemic inflammatory response syndrome following burns is mediated by brain natriuretic peptide/natriuretic peptide A receptor-induced shock factor 1 signaling pathway. AB - The aim of this study was to determine whether systemic inflammatory response syndrome (SIRS) in burn patients is mediated by the brain natriuretic peptide (BNP)/natriuretic peptide A receptor (NPRA)-induced heat shock factor 1 (HSF-1) signalling pathway. Mononuclear cells (MNCs) that were isolated from patients with burn injuries and SIRS mouse models and a RAW264.7 cell line were treated with normal serum or serum obtained from animals with burn injuries. In parallel, small hairpin RNAs (shRNAs) against BNP or NPRA were transfected in both cell types. Western blotting (WB) and enzyme-linked immunosorbent assay (ELISA) were used to detect protein expression and inflammatory factor levels, respectively. We found that interleukin (IL)-12, tumour necrosis factor (TNF)-alpha, C-reactive protein (CRP), and BNP levels were increased and IL-10 levels were decreased in the plasma and MNCs in vivo in the animal model of SIRS. Additionally, NPRA was upregulated, whereas HSF-1 was downregulated in monocytes in vivo. Treatment of RAW264.7 cells with burn serum or BNP induced IL-12, TNF-alpha, and CRP secretion as well as HSF-1 expression. Finally, silencing BNP with shRNA interrupted the effect of burn serum on RAW264.7 cells, and silencing NPRA blocked burn serum- and BNP-mediated changes in RAW264.7 cells. These results suggest that the interaction of NPRA with BNP secreted from circulatory MNCs as well as mononuclear macrophages leads to inflammation via HSF-1 during SIRS development following serious burn injury. PMID- 27385585 TI - Paediatric European Network for Treatment of AIDS Treatment Guideline 2016 update: antiretroviral therapy recommended for all children living with HIV. PMID- 27385586 TI - Parkinson Disease-linked Vps35 R524W Mutation Impairs the Endosomal Association of Retromer and Induces alpha-Synuclein Aggregation. AB - Endosomal sorting is a highly orchestrated cellular process. Retromer is a heterotrimeric complex that associates with endosomal membranes and facilitates the retrograde sorting of multiple receptors, including the cation-independent mannose 6-phosphate receptor for lysosomal enzymes. The cycling of retromer on and off the endosomal membrane is regulated by a network of retromer-interacting proteins. Here, we find that Parkinson disease-associated Vps35 variant, R524W, but not P316S, is a loss-of-function mutation as marked by a reduced association with this regulatory network and dysregulation of endosomal receptor sorting. Expression of Vps35 R524W-containing retromer results in the accumulation of intracellular alpha-synuclein-positive aggregates, a hallmark of Parkinson disease. Overall, the Vps35 R524W-containing retromer has a decreased endosomal association, which can be partially rescued by R55, a small molecule previously shown to stabilize the retromer complex, supporting the potential for future targeting of the retromer complex in the treatment of Parkinson disease. PMID- 27385587 TI - Functional Human alpha7 Nicotinic Acetylcholine Receptor (nAChR) Generated from Escherichia coli. AB - Human Cys-loop receptors are important therapeutic targets. High-resolution structures are essential for rational drug design, but only a few are available due to difficulties in obtaining sufficient quantities of protein suitable for structural studies. Although expression of proteins in E. coli offers advantages of high yield, low cost, and fast turnover, this approach has not been thoroughly explored for full-length human Cys-loop receptors because of the conventional wisdom that E. coli lacks the specific chaperones and post-translational modifications potentially required for expression of human Cys-loop receptors. Here we report the successful production of full-length wild type human alpha7nAChR from E. coli Chemically induced chaperones promote high expression levels of well-folded proteins. The choice of detergents, lipids, and ligands during purification determines the final protein quality. The purified alpha7nAChR not only forms pentamers as imaged by negative-stain electron microscopy, but also retains pharmacological characteristics of native alpha7nAChR, including binding to bungarotoxin and positive allosteric modulators specific to alpha7nAChR. Moreover, the purified alpha7nAChR injected into Xenopus oocytes can be activated by acetylcholine, choline, and nicotine, inhibited by the channel blockers QX-222 and phencyclidine, and potentiated by the alpha7nAChR specific modulators PNU-120596 and TQS. The successful generation of functional human alpha7nAChR from E. coli opens a new avenue for producing mammalian Cys loop receptors to facilitate structure-based rational drug design. PMID- 27385589 TI - Sneaker Male Squid Produce Long-lived Spermatozoa by Modulating Their Energy Metabolism. AB - Spermatozoa released by males should remain viable until fertilization. Hence, sperm longevity is governed by intrinsic and environmental factors in accordance with the male mating strategy. However, whether intraspecific variation of insemination modes can impact sperm longevity remains to be elucidated. In the squid Heterololigo bleekeri, male dimorphism (consort and sneaker) is linked to two discontinuous insemination modes that differ in place and time. Notably, only sneaker male spermatozoa inseminated long before egg spawning can be stored in the seminal receptacle. We found that sneaker spermatozoa exhibited greater persistence in fertilization competence and flagellar motility than consort ones because of a larger amount of flagellar glycogen. Sneaker spermatozoa also showed higher capacities in glucose uptake and lactate efflux. Lactic acidosis was considered to stabilize CO2-triggered self-clustering of sneaker spermatozoa, thus establishing hypoxia-induced metabolic changes and sperm survival. These results, together with comparative omics analyses, suggest that postcopulatory reproductive contexts define sperm longevity by modulating the inherent energy levels and metabolic pathways. PMID- 27385591 TI - Film clips and narrative text as subjective emotion elicitation techniques. AB - Film clips and narrative text are useful techniques in eliciting emotion in a laboratory setting but have not been examined side-by-side using the same methodology. This study examined the self-identification of emotions elicited by film clip and narrative text stimuli to confirm that selected stimuli appropriately target the intended emotions. Seventy participants viewed 30 film clips, and 40 additional participants read 30 narrative texts. Participants identified the emotion experienced (happy, sad, angry, fearful, neutral-six stimuli each). Eighty-five percent of participants self-identified the target emotion for at least two stimuli for all emotion categories of film clips, except angry (only one) and for all categories of narrative text, except fearful (only one). The most effective angry text was correctly identified 74% of the time. Film clips were more effective in eliciting all target emotions in participants for eliciting the correct emotion (angry), intensity rating (happy, sad), or both (fearful). PMID- 27385588 TI - A Novel Allosteric Activator of Free Fatty Acid 2 Receptor Displays Unique Gi functional Bias. AB - The short chain fatty acid receptor FFA2 is able to stimulate signaling via both Gi- and Gq/G11-promoted pathways. These pathways are believed to control distinct physiological end points but FFA2 receptor ligands appropriate to test this hypothesis have been lacking. Herein, we characterize AZ1729, a novel FFA2 regulator that acts as a direct allosteric agonist and as a positive allosteric modulator, increasing the activity of the endogenously produced short chain fatty acid propionate in Gi-mediated pathways, but not at those transduced by Gq/G11 Using AZ1729 in combination with direct inhibitors of Gi and Gq/G11 family G proteins demonstrated that although both arms contribute to propionate-mediated regulation of phospho-ERK1/2 MAP kinase signaling in FFA2-expressing 293 cells, the Gq/G11-mediated pathway is predominant. We extend these studies by employing AZ1729 to dissect physiological FFA2 signaling pathways. The capacity of AZ1729 to act at FFA2 receptors to inhibit beta-adrenoreceptor agonist-promoted lipolysis in primary mouse adipocytes and to promote chemotaxis of isolated human neutrophils confirmed these as FFA2 processes mediated by Gi signaling, whereas, in concert with blockade by the Gq/G11 inhibitor FR900359, the inability of AZ1729 to mimic or regulate propionate-mediated release of GLP-1 from mouse colonic preparations defined this physiological response as an end point transduced via activation of Gq/G11. PMID- 27385590 TI - Recognition of the Major Histocompatibility Complex (MHC) Class Ib Molecule H2 Q10 by the Natural Killer Cell Receptor Ly49C. AB - Murine natural killer (NK) cells are regulated by the interaction of Ly49 receptors with major histocompatibility complex class I molecules (MHC-I). Although the ligands for inhibitory Ly49 were considered to be restricted to classical MHC (MHC-Ia), we have shown that the non-classical MHC molecule (MHC Ib) H2-M3 was a ligand for the inhibitory Ly49A. Here we establish that another MHC-Ib, H2-Q10, is a bona fide ligand for the inhibitory Ly49C receptor. H2-Q10 bound to Ly49C with a marginally lower affinity (~5 MUm) than that observed between Ly49C and MHC-Ia (H-2K(b)/H-2D(d), both ~1 MUm), and this recognition could be prevented by cis interactions with H-2K in situ To understand the molecular details underpinning Ly49.MHC-Ib recognition, we determined the crystal structures of H2-Q10 and Ly49C bound H2-Q10. Unliganded H2-Q10 adopted a classical MHC-I fold and possessed a peptide-binding groove that exhibited features similar to those found in MHC-Ia, explaining the diverse peptide binding repertoire of H2-Q10. Ly49C bound to H2-Q10 underneath the peptide binding platform to a region that encompassed residues from the alpha1, alpha2, and alpha3 domains, as well as the associated beta2-microglobulin subunit. This docking mode was conserved with that previously observed for Ly49C.H-2K(b) Indeed, structure-guided mutation of Ly49C indicated that Ly49C.H2-Q10 and Ly49C.H-2K(b) possess similar energetic footprints focused around residues located within the Ly49C beta4-stand and L5 loop, which contact the underside of the peptide-binding platform floor. Our data provide a structural basis for Ly49.MHC-Ib recognition and demonstrate that MHC-Ib represent an extended family of ligands for Ly49 molecules. PMID- 27385593 TI - The Relationship Between Glutathione S-Transferase-P1 and Beta-2 Adrenoreceptor Genotypes with Asthmatic Patients in the Turkish Population. AB - BACKGROUND: Individual differences in the activity of enzymes that metabolize xenobiotics can impact health and disease. Beta-2 adrenoreceptor (ADRB2) is a functional G-coupled protein expressed in the vascular endothelium of lungs, alveolar walls, and the ganglions of cholinergic nerves which induces bronchodilation in response to catecholamines. Glutathione S-Transferase-P1 (GSTP1) is a candidate pi class GST gene, which controls pi class glutathione S transferase activity. AIMS: In this study we determined the relationship between the ADRB2 Arg16Gly polymorphism and GSTP1 polymorphisms, involved in bronchodilator response and oxidative stress, respectively, with susceptibility to asthma. METHODS: In this study, 129 asthmatic patients and 127 healthy control cases were recruited to determine ADRB2 and GSTP1 genotypes by allele-specific polymerase chain reaction and restriction fragment length polymorphism assays, respectively. RESULTS: The ADRB2 genotype frequencies of the patients and control cases were found to be 10.9% (Arg16Arg), 48.8% (Arg16Gly), and 40.3% (Gly16Gly) and 24.4% (Arg16Arg), 36.2% (Arg16Gly), and 39.4% (Gly16Gly), respectively. GSTP1 genotype frequencies of patients and control cases were found to be 55% (Ile105Ile), 43.4% (Ile105Val), and 1.6% (Val105Val) and 75.6% (Ile105Ile), 22% (Ile105Val), and 2.4% (Val105Val), respectively. In the case of the GSTP1 gene, we found statistically significant differences in the genotype frequency of Ile105Val and the allele frequency of Val105 in the asthmatic group compared with the controls. Moreover, we observed a relationship between allele frequencies and clinical phenotypes including atopia nocturnal dyspnea, and steroid dependency in the asthmatic patients. CONCLUSION: Our results suggest that the GSTP1 Ile105Val polymorphism may be linked to the severeness of airway dysfunction. PMID- 27385592 TI - Protease activated receptor 1 (PAR1) enhances Src-mediated tyrosine phosphorylation of NMDA receptor in intracerebral hemorrhage (ICH). AB - It has been demonstrated that Src could modulate NMDA receptor, and PAR1 could also affect NMDAR signaling. However, whether PAR1 could regulate NMDAR through Src under ICH has not yet been investigated. In this study, we demonstrated the role of Src-PSD95-GluN2A signaling cascades in rat ICH model and in vitro thrombin challenged model. Using the PAR1 agonist SFLLR, antagonist RLLFS and Src inhibitor PP2, electrophysiological analysis showed that PAR1 regulated NMDA induced whole-cell currents (INMDA) though Src in primary cultured neurons. Both in vivo and in vitro results showed the elevated phosphorylation of tyrosine in Src and GluN2A and enhanced interaction of the Src-PSD95-GluN2A under model conditions. Treatment with the PAR1 antagonist RLLFS, AS-PSD95 (Antisense oligonucleotide against PSD95) and Src inhibitor PP2 inhibited the interaction among Src-PSD95-GluN2A, and p-Src, p-GluN2A. Co-application of SFLLR and AS PSD95, PP2, or MK801 (NMDAR inhibitor) abolished the effect of SF. In conclusion, our results demonstrated that activated thrombin receptor PAR1 induced Src activation, enhanced the interaction among Src-PSD95-GluN2A signaling modules, and up-regulated GluN2A phosphorylation after ICH injury. Elucidation of such signaling cascades would possibly provide novel targets for ICH treatment. PMID- 27385594 TI - Original Research: Feasibility and safety of two surgical techniques for the development of an animal model of jugular vein occlusion. AB - To date, no studies have explored the effect of abnormal cerebral venous circulation on brain disorders, whereas many studies have investigated neurodegenerative brain anomalies associated with arterial diseases. The aim of our study was to demonstrate the feasibility of different surgical techniques to induce venous obstruction of cerebral brain drainage. Six C57/black mice underwent bilateral occlusion of the external jugular vein (group EJV), six underwent bilateral occlusion of the internal jugular vein (group IJV), and six underwent bilateral occlusion of both the EJV and the IJV (group EJV/IJV). Within each group, the interruption of blood flow was obtained via monopolar electro coagulation (ME) in three mice and via surgical ligation (SL) in the remaining three mice. A "sham group" of two mice was used as the control. High-frequency ultrasound (HFUS) was used to detect the absence of blood flow in the examined vessel. The ME procedure led to successful results in two of nine (22%) mice, one in the EJV group, one in the EJV/IJV group, and zero in the IJV group, and 4 of 18 (22%) mice when considering individual veins (i.e., total number of EJVs and IJVs occluded). The SL procedure was successful in two of three (67%) mice in the EJV group, in three of three (100%) mice in the IJV and in three of four (75%) mice in the EJV/IJV group. Therefore, the overall success rate was 8/10 (80%) when considering mice, and 20/26 (77%) when considering individual veins. The monopolar electro-coagulation method exhibited a high mortality due to cardiorespiratory arrest, while the results of the bilateral surgical ligation of EJVs and IJVs show that it is technically feasible and safe. PMID- 27385597 TI - Direct Regulation of Extracellular Chitinase Production by the Transcription Factor LeClp in Lysobacter enzymogenes OH11. AB - Lysobacter enzymogenes is a gram-negative bacterial biological control agent that produces abundant extracellular enzymes capable of degrading the cell walls of fungal pathogens. In strain OH11, an isolate from China, the global regulator LeClp controls the production of extracellular chitinase by regulating the transcription of the chitinase-encoding gene chiA. Using a combination of bioinformatic, genetic, and biochemical methods, we show that LeClp regulates chiA transcription by directly binding to the chiA promoter region. Although LeClp appears to be important in this role, it is not the sole regulator of chiA transcription. Furthermore, the sequence analysis of putative LeClp binding sites indicated that the LeClp homolog could be involved in the regulation of extracellular chitinase production in diverse Lysobacter spp. by a mechanism similar to that in L. enzymogenes. Our findings present new insights into the molecular mechanism of LeClp in controlling extracellular chitinase activity, providing a fundamental road to elucidate how LeClp regulates the production of other extracellular lytic enzymes in L. enzymogenes. PMID- 27385595 TI - Cell sources for in vitro human liver cell culture models. AB - In vitro liver cell culture models are gaining increasing importance in pharmacological and toxicological research. The source of cells used is critical for the relevance and the predictive value of such models. Primary human hepatocytes (PHH) are currently considered to be the gold standard for hepatic in vitro culture models, since they directly reflect the specific metabolism and functionality of the human liver; however, the scarcity and difficult logistics of PHH have driven researchers to explore alternative cell sources, including liver cell lines and pluripotent stem cells. Liver cell lines generated from hepatomas or by genetic manipulation are widely used due to their good availability, but they are generally altered in certain metabolic functions. For the past few years, adult and pluripotent stem cells have been attracting increasing attention, due their ability to proliferate and to differentiate into hepatocyte-like cells in vitro However, controlling the differentiation of these cells is still a challenge. This review gives an overview of the major human cell sources under investigation for in vitro liver cell culture models, including primary human liver cells, liver cell lines, and stem cells. The promises and challenges of different cell types are discussed with a focus on the complex 2D and 3D culture approaches under investigation for improving liver cell functionality in vitro Finally, the specific application options of individual cell sources in pharmacological research or disease modeling are described. PMID- 27385596 TI - Inhibition of microRNA-34a prevents IL-1beta-induced extracellular matrix degradation in nucleus pulposus by increasing GDF5 expression. AB - Accumulating evidence indicates that miRNAs, a class of small non-coding RNAs, are implicated in the pathogenesis of various diseases such as cancer and intervertebral disc degeneration. The aim of this study was to investigate the expression and the biological function of microRNA-34a in intervertebral disc degeneration. In this study, microRNA-34a expression was assessed in nucleus pulposus specimens and in IL-1beta-stimulated nucleus pulposus cells by real-time polymerase chain reaction. microRNA-34a functions were investigated by using gain and loss of function experiments in nucleus pulposus cells and a dual luciferase reporter assay in 293T cells. microRNA-34a was dramatically up-regulated in degenerative nucleus pulposus tissues and in IL-1beta-stimulated nucleus pulposus cells when compared with controls. Furthermore, growth differentiation factor 5 was identified as a target of microRNA-34a. Aberrant expression of microRNA-34a inhibited growth differentiation factor 5 expression by direct binding to its 3' untranslated region. This inhibition was abolished by mutation of the microRNA 34a binding sites. In addition, microRNA-34a silencing reversed IL-1beta-induced decrease in type II collagen and aggrecan expression in nucleus pulposus cells. This effect was substantially suppressed by growth differentiation factor 5 silencing. Our results suggested that microRNA-34a inhibition prevents IL-1beta induced extracellular matrix degradation in human nucleus pulposus by increasing growth differentiation factor 5 expression. microRNA-34a inhibition may be a novel molecular target for intervertebral disc degeneration treatment through the prevention of nucleus pulposus extracellular matrix degradation. PMID- 27385598 TI - Novel Alleviation Mechanisms of Aluminum Phytotoxicity via Released Biosilicon from Rice Straw-Derived Biochars. AB - Replacing biosilicon and biocarbon in soil via biochar amendment is a novel approach for soil amelioration and pollution remediation. The unique roles of silicon (Si)-rich biochar in aluminum (Al) phytotoxicity alleviation have not been discovered. In this study, the alleviation of Al phytotoxicity to wheat plants (root tips cell death) by biochars fabricated from rice straw pyrolyzed at 400 and 700 degrees C (RS400 and RS700) and the feedstock (RS100) were studied using a slurry system containing typical acidic soils for a 15-day exposure experiment. The distributions of Al and Si in the slurry solution, soil and plant root tissue were monitored by staining methods, chemical extractions and SEM-EDS observations. We found that the biological sourced silicon in biochars served dual roles in Al phytotoxicity alleviation in acidic soil slurry. On one hand, the Si particles reduced the amount of soil exchangeable Al and prevented the migration of Al to the plant. More importantly, the Si released from biochars synchronously absorbed by the plants and coordinated with Al to form Al-Si compounds in the epidermis of wheat roots, which is a new mechanism for Al phytotoxicity alleviation in acidic soil slurry by biochar amendment. In addition, the steady release of Si from the rice straw-derived biochars was a sustainable Si source for aluminosilicate reconstruction in acidic soil. PMID- 27385599 TI - Leukoreduced red blood cell transfusions do not induce platelet glycoprotein antibodies in patients with sickle cell disease. AB - BACKGROUND: Alloimmunization to red blood cell (RBC) antigens after transfusion is well described in patients with sickle cell disease (SCD). We recently demonstrated that leukocyte-reduced RBC transfusions appeared to induce human leukocyte antigen (HLA) antibodies in some children with SCD; now, we hypothesize that residual platelets contained in transfused RBC products may lead to platelet glycoprotein antibody formation. STUDY DESIGN AND METHODS: A cross-sectional study was conducted among never pregnant pediatric patients with SCD who either had received many RBC transfusions or had never received any transfusions. Serum was tested for antibodies to platelet-specific glycoproteins using a commercial enzyme immunoassay. RESULTS: Platelet-specific glycoprotein antibodies were found in 12 of 90 patients (13%) in the transfused group versus 5 of 24 patients (21%) in the never transfused group (p = 0.35). The prevalence of antibodies as well as the median standardized optical density for these two groups was not significantly different for any of the studied platelet glycoprotein antigens. There was no association with the presence of platelet-specific glycoprotein antibodies with either RBC or HLA antibodies. CONCLUSIONS: Leukocyte-reduced RBC transfusions do not appear to induce platelet-specific glycoprotein antibodies. The positive platelet-specific glycoprotein antibody results from this study may represent platelet autoantibodies, platelet alloantibodies, or false-positive reactions. A better understanding of the immunobiology of patients with SCD at baseline and after blood product exposure may help improve future transfusion and transplantation. PMID- 27385600 TI - Periodontitis May Deteriorate Sinus of Valsalva Dilatation in Marfan Syndrome Patients. AB - Marfan syndrome (MFS) is a systemic connective tissue disorder that is caused by mutations of fibrillin-1. While MFS patients are at a high risk of periodontitis and aortic diseases, little causal information has been provided to date. To clarify the relationship, their oral condition and sinus of Valsalva (SoV) were evaluated.The subjects were patients with MFS (n = 33) who attended the University of Tokyo Hospital. We divided them into two groups; MFS patients with highly dilated (the diameters were equal to or more than 39 mm) SoV (high group, n = 18) and MFS patients with mildly dilated (less than 39 mm) SoV (mild group, n = 15). Blood examinations, echocardiograms, and full-mouth clinical measurements, including number of teeth, probing pocket depth (PPD), bleeding on probing (BOP), and community periodontal index (CPI) were performed.We found that the high group patients had greater rates of BOP compared to that of the mild group. Furthermore, the high group tended to have higher serum levels of C-reactive protein, matrix metalloproteinase-9, and transforming growth factor-beta compared to the mild group.Periodontitis may deteriorate SoV dilatation in MFS patients. PMID- 27385601 TI - Synchronization of the Flow and Pressure Waves Obtained With Non-Simultaneous Multipoint Measurements. AB - The use of measured data as boundary conditions renders hemodynamic simulations more patient-specific. However, synchronized acquisition of data at multiple locations is often difficult in clinical practice. This study proposes a method for resynchronizing measured data for use as boundary conditions for flow simulations using frequency analyses, and discusses the optimal cut-off frequency for differentiating cardiac and respiratory variation in hemodynamic data during resynchronization. To demonstrate the utility of the method, a Fontan circulation, which is the final palliative result with single-ventricle physiology, was used. The results suggest that it is optimal to set a cut-off frequency that gives a local minimum in the power spectrum that is slightly lower than the peak frequency of the heartbeat. Additionally, the total energy loss depended on the cut-off frequency, although the overall flow patterns appeared to be similar. The method is applicable to cardiovascular systems other than the Fontan circulation, where hemodynamic data with multifactorial fluctuations are required at various locations but simultaneous measurements are not possible. PMID- 27385602 TI - Hypertrophic Cardiomyopathy Accompanied by Spinocerebellar Atrophy With a Novel Mutation in Troponin I Gene. AB - We report the case of a 66 year-old woman with chronic atrial fibrillation, hypertrophic cardiomyopathy (HCM), and spinocerebellar atrophy (SCA). Her mother and first-born son had died of heart disease at the ages of 65 and 16 years, respectively. Four of her 8 siblings had died suddenly of unknown cause or of heart disease, and 2 others of cerebral infarction by the 7th decade. Genetic testing revealed that she had a novel mutation (c. 482C > A, p. Ala161Asp) in the troponin I gene (TNNI3), and no abnormality of the GAA repeat in the frataxin gene. Her older brother with SCA but without HCM was also analyzed, with no abnormality noted in either gene. The Ala161Asp mutation in TNNI3 was implicated in the pathogenesis of her HCM, though an association between HCM and SCA was not revealed. PMID- 27385603 TI - Comparative Effectiveness of Oral Medications for Pulmonary Arterial Hypertension. AB - Pulmonary arterial hypertension (PAH) is a disease that imposes a significant burden on patients. Although multiple treatment options for PAH are available, head-to-head comparisons are difficult to conduct. Network meta-analysis (NMA) can be a useful alternative for direct comparison to estimate the relative effectiveness of multiple treatments. The objective of the present study was to conduct a systematic review and NMA to evaluate the relative effectiveness among oral PAH medications.Data collection was performed by searching the Cochrane Central Register of Controlled Trials (CENTRAL) and Ichushi-Web. Randomized controlled trials (RCTs) assessing at least 1 of the following 3 outcome measurements; 6-minute walk distance test (6MWD), WHO functional class (WHOFC), and mean pulmonary artery pressure (mPAP) were included (PROSPERO registration number: CRD42015016557). Outcomes were evaluated by estimating the differences in the mean change from baseline or by estimating the odds ratios. Analyses were performed using WinBUGS 1.4.3.Seven double-blind RCTs were eligible. NMA results showed similar improvements in 6MWD for all medications assessed. Bosentan and sildenafil caused a statistically significant improvement in WHOFC compared to other medications.The relative effectiveness of oral PAH medications could be compared using NMA, which suggested the superiority of bosentan and sildenafil in the improvement of WHOFC. PMID- 27385604 TI - Restoration of Mitral Inflow Velocity Until Blanking Period Is Associated With Successful Ablation for Persistent Atrial Fibrillation. AB - Radiofrequency catheter ablation (RFCA) is a useful therapeutic option for atrial fibrillation (AF), although outcomes are less effective for persistent AF. The aim of this study was to elucidate the echocardiographic parameters associated with successful RFCA in patients with persistent AF.A total of 159 patients (mean age, 60.8 +/- 9.6 years, 125 males [78.6%]) who underwent RFCA for persistent AF from April 2009 to May 2014 were included, retrospectively. Transthoracic echocardiography was performed at baseline, 3 months, 6 months, and 1 year following RFCA. The subjects were divided into 2 groups, a recurrence group and a non-recurrence group. One hundred eleven of the 159 patients (69.8%) remained free from recurrent atrial tachyarrhythmia during follow-up (mean, 20.6 +/- 17.4 months). Peak A wave velocity (38.1 +/- 14.1 in the recurrence group; 48.0 +/- 20.7 in the non-recurrence group, P = 0.01), peak E wave velocity (76.4 +/- 19.1 versus 68.8 +/- 19.5, P = 0.03), deceleration time (196.3 +/- 54.4 versus 219.9 +/- 64.1, P = 0.04), and left atrial (LA) diameter (44.5 +/- 7.3 versus 41.0 +/- 5.6, P = 0.01) at 3 months after ablation were significantly different between the two groups. Among echocardiographic parameters, peak A wave velocity (OR 0.96, 95% confidence interval [CI] 0.92-0.99) and LA diameter (OR 1.13, 95% CI 1.011.25) were associated with AF recurrence.After RFCA for persistent AF, LA anatomical and functional changes occurred during a 3-month blanking period. Restoration of peak A wave velocity and LA size are associated with successful ablation. PMID- 27385605 TI - Late-Onset Postoperative Junctional Ectopic Tachycardia in Nonsurgical Procedures. AB - Postoperative junctional ectopic tachycardia (JET) is a narrow complex tachycardia and most frequently occurs during and after surgical repair of certain types of congenital heart defects. Postoperative junctional ectopic tachycardia may produce unfavorable hemodynamics that prolongs stays in the cardiac intensive care unit and hospital, prolongs time on a ventilator, and occasionally requires the use of extracorporeal membrane oxygenation (ECMO) as rescue therapy. The present report describes a rare case of late-onset postoperative junctional ectopic tachycardia, which occurred 13 days after the deployment of a perimembranous ventricular septal defect (PmVSD) occluder in a 17 year-old female teenager. To the best of our knowledge, late-onset postoperative junctional ectopic tachycardia has not previously been reported as a complication in nonsurgical procedures. In this case, the junctional ectopic tachycardia remained resistant to medicines and the haemodynamic imbalance caused a serious life-threatening situation in the patient. The occluder was removed by an emergent thoracotomy; then, the patient was successfully cured by being supported with extracorporeal membrane oxygenation. The findings suggest that during follow up management, the physician should pay attention postoperatively to junctional ectopic tachycardia even after discharge from the hospital. PMID- 27385606 TI - Fontan-Like Hemodynamics Complicated With Ventricular Fibrillation During Left Ventricular Assist Device Support. AB - We experienced a patient who had received an implantable continuous-flow left ventricular assist device (LVAD) (HeartMate II, Thoratec Corp, Pleasanton, CA, USA) and was admitted to our hospital because of repeated ventricular tachyarrhythmias refractory to electrical defibrillation as well as intensive pharmacological therapy. We decided to discontinue defibrillating, but under ventricular fibrillation his hemodynamics were maintained without end-organ dysfunction during LVAD support (mean right atrial pressure 18 mmHg; pulmonary vascular resistance 1.6 WU; pulmonary capillary wedge pressure 11 mmHg; cardiac index 2.04 L/minute/m(2)) due to optimization of the rotation speed (from 8800 to 9200 rpm). Such "Fontan-like circulation" could be accomplished by adequate volume control, lowering pulmonary vascular resistance, and potent LV blood removal by optimal rotation speed of the LVAD, although the precise conditions to maintain the Fontan-like circulation during LVAD therapy remained uncertain. Considering the severe donor heart shortage and high degree of difficulty of the catheter ablation procedure to manage ventricular tachyarrhythmias, constructing a Fontan-like circulation in the presence of ventricular tachyarrhythmias may be one unique strategy. Longterm prognosis in patients with sustained ventricular tachyarrhythmias during LVAD support would be a future concern. PMID- 27385607 TI - Real-Time Assessment of Autonomic Nerve Activity During Adaptive Servo Ventilation Support or Waon Therapy. AB - Adaptive servo-ventilation support and Waon therapy are recently developed non pharmacological and noninvasive therapies for patients with heart failure refractory to guideline-directed medical therapy. These therapies decrease both preload and afterload, increase cardiac output, and appear to ameliorate autonomic nerve activity. However, the time course of autonomic nerve activity during these therapies remains unclear. We performed heart rate variability analysis using the MemCalc power spectral density method (MemCalc system; Suwa Trust Co, Tokyo) to assess autonomic nerve activity during adaptive servo ventilation support and Waon therapy in two different cases and determined the time course of autonomic nerve activity during these therapies. During both therapies, we found a drastic increase in parasympathetic nerve activity and continuous suppression of sympathetic nerve activity. Heart rate variability analysis using the MemCalc method may be promising for the assessment of the efficacy of various treatments, including adaptive servo-ventilation support and Waon therapy, from the viewpoint of autonomic nerve activity. PMID- 27385608 TI - Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men. AB - BACKGROUND: The carbohydrate-insulin model of obesity posits that habitual consumption of a high-carbohydrate diet sequesters fat within adipose tissue because of hyperinsulinemia and results in adaptive suppression of energy expenditure (EE). Therefore, isocaloric exchange of dietary carbohydrate for fat is predicted to result in increased EE, increased fat oxidation, and loss of body fat. In contrast, a more conventional view that "a calorie is a calorie" predicts that isocaloric variations in dietary carbohydrate and fat will have no physiologically important effects on EE or body fat. OBJECTIVE: We investigated whether an isocaloric low-carbohydrate ketogenic diet (KD) is associated with changes in EE, respiratory quotient (RQ), and body composition. DESIGN: Seventeen overweight or obese men were admitted to metabolic wards, where they consumed a high-carbohydrate baseline diet (BD) for 4 wk followed by 4 wk of an isocaloric KD with clamped protein. Subjects spent 2 consecutive days each week residing in metabolic chambers to measure changes in EE (EEchamber), sleeping EE (SEE), and RQ. Body composition changes were measured by dual-energy X-ray absorptiometry. Average EE during the final 2 wk of the BD and KD periods was measured by doubly labeled water (EEDLW). RESULTS: Subjects lost weight and body fat throughout the study corresponding to an overall negative energy balance of ~300 kcal/d. Compared with BD, the KD coincided with increased EEchamber (57 +/- 13 kcal/d, P = 0.0004) and SEE (89 +/- 14 kcal/d, P < 0.0001) and decreased RQ (-0.111 +/- 0.003, P < 0.0001). EEDLW increased by 151 +/- 63 kcal/d (P = 0.03). Body fat loss slowed during the KD and coincided with increased protein utilization and loss of fat-free mass. CONCLUSION: The isocaloric KD was not accompanied by increased body fat loss but was associated with relatively small increases in EE that were near the limits of detection with the use of state-of-the-art technology. This trial was registered at clinicaltrials.gov as NCT01967563. PMID- 27385609 TI - Genetic and environmental influences on food preferences in adolescence. AB - BACKGROUND: Food preferences vary substantially among adults and children. Twin studies have established that genes and aspects of the shared family environment both play important roles in shaping children's food preferences. The transition from childhood to adulthood is characterized by large gains in independence, but the relative influences of genes and the environment on food preferences in late adolescence are unknown. OBJECTIVE: The aim of this study was to quantify the contribution of genetic and environmental influences on food preferences in older adolescents. DESIGN: Participants were 2865 twins aged 18-19 y from the TEDS (Twins Early Development Study), a large population-based cohort of British twins born during 1994-1996. Food preferences were measured by using a self-report questionnaire of 62 individual foods. Food items were categorized into 6 food groups (fruit, vegetables, meat or fish, dairy, starch foods, and snacks) by using factor analysis. Maximum likelihood structural equation modeling established genetic and environmental contributions to variations in preferences for each food group. RESULTS: Genetic factors influenced a significant and substantial proportion of the variation in preference scores of all 6 food groups: vegetables (0.54; 95% CI: 0.47, 0.59), fruit (0.49; 95% CI: 0.43, 0.55), starchy foods (0.32; 95% CI: 0.24, 0.39), meat or fish (0.44; 95% CI: 0.38, 0.51), dairy (0.44; 95% CI: 0.37, 0.50), and snacks (0.43; 95% CI: 0.36, 0.49). Aspects of the environment that are not shared by 2 twins in a family explained all of the remaining variance in food preferences. CONCLUSIONS: Food preferences had a moderate genetic basis in late adolescence, in keeping with findings in children. However, by this older age, the influence of the shared family environment had disappeared, and only aspects of the environment unique to each individual twin influenced food preferences. This finding suggests that shared environmental experiences that influence food preferences in childhood may not have effects that persist into adulthood. PMID- 27385610 TI - The vitamin D status of the US population from 1988 to 2010 using standardized serum concentrations of 25-hydroxyvitamin D shows recent modest increases. AB - BACKGROUND: Temporal trends in the US population's vitamin D status have been uncertain because of nonstandardized serum 25-hydroxyvitamin D [25(OH)D] measurements. OBJECTIVE: To accurately assess vitamin D status trends among those aged >=12 y, we used data from the cross-sectional NHANESs. DESIGN: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring 25(OH)D (sum of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3), calibrated to standard reference materials, was used to predict LC-MS/MS-equivalent concentrations from radioimmunoassay data (1988-2006 surveys; n = 38,700) and to measure LC-MS/MS concentrations (2007-2010 surveys; n = 12,446). Weighted arithmetic means and the prevalence of 25(OH)D above or below cutoff concentrations were calculated to evaluate long-term trends. RESULTS: Overall, mean predicted 25(OH)D showed no time trend from 1988 to 2006, but during 2007-2010 the mean measured 25(OH)D was 5-6 nmol/L higher. Those groups who showed the largest 25(OH)D increases (7-11 nmol/L) were older, female, non-Hispanic white, and vitamin D supplement users. During 1988-2010, the proportions of persons with 25(OH)D <40 nmol/L were 14-18% (overall), 46-60% (non-Hispanic blacks), 21-28% (Mexican Americans), and 6-10% (non-Hispanic whites). CONCLUSIONS: An accurate method for measuring 25(OH)D showed stable mean concentrations in the US population (1988-2006) and recent modest increases (2007-2010). Although it is unclear to what extent supplement usage compared with different laboratory methods explain the increases in 25(OH)D, the use of higher vitamin D supplement dosages coincided with the increase. Marked race-ethnic differences in 25(OH)D concentrations were apparent. These data provide the first standardized information about temporal trends in the vitamin D status of the US population. PMID- 27385611 TI - Postprandial alterations in whole-blood DNA methylation are mediated by changes in white blood cell composition. AB - BACKGROUND: DNA methylation is an essential nuclear process associated with genomic functions such as transcription factor binding and the regulation of gene expression. DNA methylation patterns can also serve as potential biomarkers for disease progression and response to therapy. However, the full dynamics of DNA methylation across daily physiologic events have not been fully elucidated. OBJECTIVE: We sought to study how ingesting a standardized meal acutely affects peripheral blood DNA methylation. DESIGN: We performed an observational study in healthy men (n = 26) on DNA methylation and gene expression in whole blood before and 160 min after the ingestion of a standardized meal. Cytosine-phosphate guanine (CpG) methylation was assayed on the HumanMethylation450k microarray, and gene expression was measured with the Human Gene 2.1 ST Array. RESULTS: Differential methylation after food intake was detected in 13% of the analyzed probes (63,207 CpG probes) at a 5% false discovery rate (FDR). This effect was driven by changes in leukocyte fractions as estimated from comparisons against methylation datasets generated from sorted leukocytes. When methylation values were adjusted for estimated leukocyte fractions, 541 probes were observed to be altered in the postprandial state (5% FDR). CONCLUSIONS: Apparent alterations in DNA methylation 160 min after meal ingestion mainly reflect changes in the estimated leukocyte population in whole blood. These results have major methodologic implications for genome-wide methylation studies because they highlight the strong underlying effects of changes in leukocyte fractions on CpG methylation patterns as well as the potential importance of meal-standardized sampling procedures for future investigations when alterations in white blood cell fractions are unavailable. This trial was registered at clinicaltrials.gov as LSF008786. PMID- 27385612 TI - Achieving the WHO sodium target: estimation of reductions required in the sodium content of packaged foods and other sources of dietary sodium. AB - BACKGROUND: Excess sodium intake is one of the top 2 dietary risk factors contributing to the global burden of disease. As such, many countries are now developing national sodium reduction strategies, a key component of which is a sodium reduction model that includes sodium targets for packaged foods and other sources of dietary sodium. OBJECTIVE: We sought to develop a sodium reduction model to determine the reductions required in the sodium content of packaged foods and other dietary sources of sodium to reduce adult population salt intake by ~30% toward the optimal WHO target of 5 g/d. DESIGN: Nationally representative household food-purchasing data for New Zealand were linked with branded food composition information to determine the mean contribution of major packaged food categories to total population sodium consumption. Discretionary salt use and the contribution of sodium from fresh foods and foods consumed away from the home were estimated with the use of national nutrition survey data. Reductions required in the sodium content of packaged foods and other dietary sources of sodium to achieve a 30% reduction in dietary sodium intakes were estimated. RESULTS: A 36% reduction (1.6 g salt or 628 mg Na) in the sodium content of packaged foods in conjunction with a 40% reduction in discretionary salt use and the sodium content of foods consumed away from the home would reduce total population salt intake in New Zealand by 35% (from 8.4 to 5.5 g/d) and thus meet the WHO 2025 30% relative reduction target. Key reductions required include a decrease of 21% in the sodium content of white bread, 27% for hard cheese, 42% for sausages, and 54% for ready-to-eat breakfast cereals. CONCLUSIONS: Achieving the WHO sodium target in New Zealand will take considerable efforts by both food manufacturers and consumers and will likely require a national government-led sodium reduction strategy. PMID- 27385613 TI - A prospective study of caffeine and coffee intake and premenstrual syndrome. AB - BACKGROUND: Clinically significant premenstrual syndrome (PMS) affects 15-20% of premenopausal women, substantially reducing quality of life. Women with PMS often are counseled to minimize caffeine intake, although only limited evidence supports this recommendation. OBJECTIVE: We evaluated the association between total caffeine, coffee, and tea intake and the development of PMS in a case control study nested within the prospective Nurses' Health Study II. DESIGN: All participants were free from PMS at baseline (1991). PMS cases reported a new clinician-made diagnosis of PMS on biennial questionnaires between 1993 and 2005, and then confirmed symptom timing and moderate-to-severe impact and severity of symptoms with the use of a retrospective questionnaire (n = 1234). Controls did not report PMS and confirmed experiencing no symptoms or few mild symptoms with limited personal impact (n = 2426). Caffeine, coffee, and tea intake was measured by food-frequency questionnaires every 4 y, and data on smoking, body weight, and other factors were updated every 2-4 y. Logistic regression was used to evaluate the associations of total caffeine intake and frequency of coffee and tea consumption with PMS. RESULTS: After adjustment for age, smoking, and other factors, total caffeine intake was not associated with PMS. The OR comparing women with the highest (quintile median = 543 mg/d) to the lowest (quintile median = 18 mg/d) caffeine intake was 0.79 (95% CI: 0.61, 1.04; P-trend = 0.31). High caffeinated coffee intake also was not associated with risk of PMS or specific symptoms, including breast tenderness (OR for >=4 cups/d compared with <1/mo: 0.73; 95% CI: 0.48, 1.12; P-trend = 0.44). CONCLUSIONS: Our findings suggest that caffeine intake is not associated with PMS, and that current recommendations for women to reduce caffeine intake may not help prevent the development of PMS. PMID- 27385615 TI - Efficient Iterative Synthesis of O-Acetylated Tri- to Pentadecasaccharides Related to the Lipopolysaccharide of Shigella flexneri Type 3 a through Di- and Trisaccharide Glycosyl Donors. AB - Protection against bacterial infections, including shigellosis, can be achieved by antibodies against the bacterial surface polysaccharide. In line with our efforts to develop vaccine candidates for shigellosis, we report herein the synthesis of penta-, deca-, and pentadecasaccharides as well as tri-, octa-, and tridecasaccharides as the endchain and intrachain fragments, respectively, of the surface polysaccharide of Shigella flexneri 3 a, a prevalent serotype. The syntheses relied on the efficiency of the trichloroacetimidate glycosylation chemistry, whereby iteration with di- and trisaccharide building blocks provided fragments made of up to three mono-O-acetylated polysaccharide repeating units. Pd(OH)2 -mediated hydrogenation/hydrogenolysis enabled the concomitant removal or conversion of up to 31 protecting groups of 4 different origins to provide the targets as propyl glycosides. Oligosaccharides comprising the octasaccharide segment were shown to display high conformational similarities in solution. PMID- 27385616 TI - Reconstruction in pediatric orthopedic trauma: the role of primary cross leg flap cover. AB - Composite defects of the leg often involve microsurgical reconstruction. Microsurgery is technically demanding in post-trauma situations in very young children. There is renewed interest in cross leg flaps in this scenario. Children aged up to 5 years, who had open fractures or exposed bones in the leg, were followed up prospectively. Eight children, with a mean age of 4 years, underwent nine flaps for extensive tissue defects over the leg and foot. Six of these flaps were cross leg flaps. No flap failed and all wounds acquired early stable cover. The cross leg flap is a useful alternative in the pediatric population in lieu of microsurgical tissue transfer. PMID- 27385614 TI - Predominantly nighttime feeding and weight outcomes in infants. AB - BACKGROUND: The influence of circadian feeding patterns on weight outcomes has been shown in animal and human studies but not in very young children. OBJECTIVE: We aimed to examine the association of infant circadian feeding patterns at 12 mo of age with subsequent growth and weight status after 1 y. DESIGN: Mothers from a Singapore birth cohort (n = 349) reported the food given to their infants and the feeding time at 12 mo of age. Predominantly daytime (pDT) (0700-1859; n = 282) and predominantly nighttime (pNT) (1900-0659; n = 67) feeding infants were defined by whether daytime energy intake was >50% or <50% of total energy intake as assessed with the use of a 24-h recall. Body mass index-for-age z scores (BAZs) were computed with the use of the WHO Child Growth Standards 2006 to determine changes in BAZs from 12 to 24 mo of age and weight status at 24 mo of age. Multivariable linear and logistic regression analyses were performed. RESULTS: Compared with pDT feeding, pNT feeding was associated with a higher BAZ gain from 12 to 24 mo of age (adjusted beta = 0.38; 95% CI: 0.11, 0.65; P = 0.006) and increased risk of becoming overweight at 24 mo of age (adjusted OR: 2.78; 95% CI: 1.11, 6.97; P = 0.029) with adjustments for maternal age, education, ethnicity, monthly household income, parity, infant BAZ at 12 mo of age, feeding mode in the first 6 mo of life, and total daily energy intake. CONCLUSIONS: Our study suggests that the role of the daily distribution of energy consumption in weight regulation begins in infancy. The feeding of infants predominantly during nighttime hours was associated with adiposity gain and risk of overweight in early childhood. The inclusion of advice on the appropriate feeding time may be considered when implementing strategies to combat childhood obesity. This trial was registered at clinicaltrials.gov as NCT01174875. PMID- 27385617 TI - Factors Associated With the Likelihood of Hospitalization Following Emergency Department Visits for Behavioral Health Conditions. AB - OBJECTIVES: Behavioral health-related emergency department (ED) visits have been linked with ED overcrowding, an increased demand on limited resources, and a longer length of stay (LOS) due in part to patients being admitted to the hospital but waiting for an inpatient bed. This study examines factors associated with the likelihood of hospital admission for ED patients with behavioral health conditions at 16 hospital-based EDs in a large urban area in the southern United States. METHODS: Using Andersen's Behavioral Model of Health Service Use for guidance, the study examined the relationship between predisposing (characteristics of the individual, i.e., age, sex, race/ethnicity), enabling (system or structural factors affecting healthcare access), and need (clinical) factors and the likelihood of hospitalization following ED visits for behavioral health conditions (n = 28,716 ED visits). In the adjusted analysis, a logistic fixed-effects model with blockwise entry was used to estimate the relative importance of predisposing, enabling, and need variables added separately as blocks while controlling for variation in unobserved hospital-specific practices across hospitals and time in years. RESULTS: Significant predisposing factors associated with an increased likelihood of hospitalization following an ED visit included increasing age, while African American race was associated with a lower likelihood of hospitalization. Among enabling factors, arrival by emergency transport and a longer ED LOS were associated with a greater likelihood of hospitalization while being uninsured and the availability of community-based behavioral health services within 5 miles of the ED were associated with lower odds. Among need factors, having a discharge diagnosis of schizophrenia/psychotic spectrum disorder, an affective disorder, a personality disorder, dementia, or an impulse control disorder as well as secondary diagnoses of suicidal ideation and/or suicidal behavior increased the likelihood of hospitalization following an ED visit. CONCLUSION: The block of enabling factors was the strongest predictor of hospitalization following an ED visit compared to predisposing and need factors. Our findings also provide evidence of disparities in hospitalization of the uninsured and racial and ethnic minority patients with ED visits for behavioral health conditions. Thus, improved access to community-based behavioral health services and an increased capacity for inpatient psychiatric hospitals for treating indigent patients may be needed to improve the efficiency of ED services in our region for patients with behavioral health conditions. Among need factors, a discharge diagnosis of schizophrenia/psychotic spectrum disorder, an affective disorder, a personality disorder, an impulse control disorder, or dementia as well as secondary diagnoses of suicidal ideation and/or suicidal behavior increased the likelihood of hospitalization following an ED visit, also suggesting an opportunity for improving the efficiency of ED care through the provision of psychiatric services to stabilize and treat patients with serious mental illness. PMID- 27385618 TI - Methotrexate treatment may prevent uveitis onset in patients with juvenile idiopathic arthritis: experiences and subgroup analysis in a cohort with frequent methotrexate use. AB - OBJECTIVES: To re-evaluate the ability of methotrexate (MTX) to prevent the onset of uveitis in Russian children with juvenile idiopathic arthritis (JIA). METHODS: The clinical charts for all consecutive patients who received a stable management for at least 2 years with or without MTX were reviewed. Patients who were given systemic medications other than MTX (except NSAID) and patients with systemic arthritis, rheumatoid factor-positive arthritis, or enthesitis-related arthritis were excluded. Each patient was examined after at least a 2-year follow-up period after the first visit to establish whether uveitis had occurred. RESULTS: A total of 281 patients with a median disease duration of 3.8 years were included. 191 patients (68%) were treated with MTX. During the observation period, 64 patients (22.8%) developed uveitis, a median of 1.6 year after disease onset. The frequency of uveitis was lower in MTX-treated than in MTX-untreated patients (11.5% vs. 46.7%, respectively, OR=6.7 (95%CI:3.7-12.3), p=0.0000001). Survival analysis confirmed that patients treated with MTX had a lower probability of developing uveitis (HR=4.35, p=0.000001). In subgroup analysis it was shown that MTX was more preventive in boys than in girls, and in patients with JIA onset age of over 5 years compared to those with disease onset less than 5 years. The data of survival analysis of MTX prevention has shown that benefits do not depend on the number of active joints and ANA status. CONCLUSIONS: MTX therapy may prevent the onset of uveitis in children with JIA. Further randomised controlled trials are required to confirm our results. PMID- 27385619 TI - Contribution of past and future self-defining event networks to personal identity. AB - Personal identity is nourished by memories of significant past experiences and by the imagination of meaningful events that one anticipates to happen in the future. The organisation of such self-defining memories and prospective thoughts in the cognitive system has received little empirical attention, however. In the present study, our aims were to investigate to what extent self-defining memories and future projections are organised in networks of related events, and to determine the nature of the connections linking these events. Our results reveal the existence of self-defining event networks, composed of both memories and future events of similar centrality for identity and characterised by similar identity motives. These self-defining networks expressed a strong internal coherence and frequently organised events in meaningful themes and sequences (i.e., event clusters). Finally, we found that the satisfaction of identity motives in represented events and the presence of clustering across events both contributed to increase in the perceived centrality of events for the sense of identity. Overall, these findings suggest that personal identity is not only nourished by representations of significant past and future events, but also depends on the formation of coherent networks of related events that provide an overarching meaning to specific life experiences. PMID- 27385620 TI - Cobalt release and complications resulting from the use of dental prostheses. AB - BACKGROUND: Cobalt release from dental prostheses has been shown to elicit allergic reactions in cobalt-allergic patients. It is therefore important to investigate whether these prostheses are possible sources of sensitization. OBJECTIVES: To assess (i) cobalt release from dental prostheses and (ii) allergic reactions to components of dental prostheses, and (iii) to investigate the oral mucosa for inflammation 1-5 years after insertion of the prostheses. METHOD: Clinical oral examination was conducted in 66 patients with 84 dental prostheses. Cobalt release from 84 functional (used) and 32 non-functional (new) prostheses was investigated with the cobalt spot test. Contact allergy was assessed by patch testing. Smear tests for Candida spp. were performed in patients showing signs of inflammation of the oral mucosa. The prostheses were assessed for biological and technical complications. RESULTS: None of the functional prostheses released cobalt, whereas this was observed in 24 of 32 non-functional prostheses. None of the patients had contact allergy to cobalt. Of the 66 patients, 11 showed signs of inflammation of the oral mucosa, 2 had oral candidiasis, 16 had ill-fitting prostheses, and all had insufficient oral hygiene. CONCLUSIONS: Dental prostheses released cobalt during the fabrication stages, but not 1-5 years after insertion. No allergic reactions were observed. Signs of inflammation were related to candidiasis, insufficient oral hygiene, and ill-fitting prostheses. PMID- 27385621 TI - Antimicrobial-resistant Escherichia coli in hospitalised companion animals and their hospital environment. AB - INTRODUCTION: Antimicrobial resistance is a growing concern with implications for animal health. This study investigated the prevalence of antimicrobial resistance among commensal and environmental Escherichia coli isolated from animals sampled in referral hospitals in the UK. MATERIALS AND METHODS: Resistant Escherichia coli isolated from animal faeces and practice environments were tested for susceptibility to antimicrobial agents. PCR and sequencing techniques were used to identify extended spectrum beta-lactamase and AmpC-producer genotypes. RESULTS: In total, 333 faecal and 257 environmental samples were collected. Multi drug resistant Escherichia coli were found in 13.1% of faecal and 8.9% of environmental samples. Extended spectrum beta-lactamase and AmpC genes were identified 14% and 7.7% of faecal samples and 8.6% and 8.6% of environmental samples, respectively. The most common extended spectrum beta-lactamase gene type detected was blaCTX-M -15 , although blaTEM-158 was detected in faecal and environmental samples from one practice. CLINICAL SIGNIFICANCE: Escherichia coli resistant to key antimicrobials were isolated from hospitalised animals and the practice environment. We identified the emergence of the inhibitor resistant and extended spectrum beta-lactamase blaTEM-158 in companion animals. Further investigation to determine risk factors for colonisation with antimicrobial resistant bacteria is needed to provide evidence for antimicrobial stewardship and infection control programmes. PMID- 27385622 TI - A review of anaemia of inflammatory disease in dogs and cats. AB - Anaemia of inflammatory disease is a common cause of anaemia in routine veterinary practice. It is most often mild to moderate, normocytic, normochromic and non-regenerative. Shortened red cell life span, inhibition of iron metabolism and impaired bone marrow response to erythropoietin all contribute to its development. Although anaemia of inflammatory disease is a well-known cause of anaemia in dogs and cats, there is a lack of epidemiological information because specific diagnostic criteria have not been established in veterinary species. Anaemia of inflammatory disease is associated with a poor outcome in various disease states in human medicine; however, its clinical significance and treatment in veterinary medicine are not well understood. This review article describes anaemia of inflammatory disease in dogs and cats and considers its potential significance. PMID- 27385624 TI - No evidence that medicinal honey reduces bacterial skin colonisation at a peripheral catheter insertion site in dogs. AB - OBJECTIVES: To determine whether topical exit-site application of medicinal honey at the catheter insertion place reduces bacterial skin colonisation. MEASUREMENTS AND RESULTS: Dogs were selected at random and divided into the honey or the control group. When the catheter was removed, an area of approximately 3*3 cm of the skin at the insertion site was sampled with a sterile cotton swab. The catheter stayed in place for a median of 84 hours. Out of 46 patients, 6 patients in the honey group and 5 out of 54 patients in the control group had a positive skin culture at the time of catheter removal (P=0.547). Infection was clinically suspected in 1 of those 11 dogs; catheter-associated complications were observed in 8 additional dogs that did not have a positive skin culture. CLINICAL SIGNIFICANCE: Few catheter-associated complications were observed. Extra attention to hygiene by working with a standardised catheter placement and handling protocol might have resulted in this low incidence. In this study topical application of a medicinal honey did not reduce bacterial skin colonisation at the insertion site of peripheral catheters in dogs. PMID- 27385623 TI - Treatment of canine aural haematoma by UK veterinarians. AB - OBJECTIVES: To survey the current treatment techniques of aural haematomas in dogs and investigate veterinary opinion regarding treatment success. METHODS: Totally 2386 emails were sent to veterinary surgeons and practices inviting them to complete an online survey. Questions investigated treatment selection for initial and repeat presentations of aural haematoma in dogs and their opinion of treatment success to prevent recurrence and for good cosmesis. RESULTS: Totally 312 email addresses were invalid, 259 questionnaires were completed (12.5% response rate) and 251 were included in analysis. On initial presentation, treatments included needle drainage with local deposition of corticosteroids (43%), surgery (29%) and needle drainage without corticosteroids (16%). Surgical procedures included linear incision with sutures alone (35%) or sutures plus stents (24%) and an S-shaped incision with sutures (23%). The most common reason to select a particular treatment was previous success (76%). Recurrent haematoma was treated more commonly with surgery (67%) than that of the initial presentation. Cosmetic results with medical management were excellent and with surgical treatment were good. CLINICAL SIGNIFICANCE: This study describes the relative popularity and perceived success of treatments used for aural haematoma in the dog. Surgery is considered more likely to definitively treat the condition with good cosmetic results. PMID- 27385625 TI - Conservative management of an atlantoaxial subluxation using thermoplastic material. PMID- 27385626 TI - Comparison of radiologically and histologically determined thickness of bone overlying the superior semicircular canal in sixty-six cadaveric specimens: impact on the diagnosis of Minor's Syndrome. PMID- 27385627 TI - Bioinspired synthesis of magnetite nanoparticles. AB - Magnetite (Fe3O4) is a widespread magnetic iron oxide encountered in many biological and geological systems, and also in many technological applications. The magnetic properties of magnetite crystals depend strongly on the size and shape of its crystals. Hence, engineering magnetite nanoparticles with specific shapes and sizes allows tuning their properties to specific applications in a wide variety of fields, including catalysis, magnetic storage, targeted drug delivery, cancer diagnostics and magnetic resonance imaging (MRI). However, synthesis of magnetite with a specific size, shape and a narrow crystal size distribution is notoriously difficult without using high temperatures and non aqueous media. Nevertheless, living organisms such as chitons and magnetotactic bacteria are able to form magnetite crystals with well controlled sizes and shapes under ambient conditions and in aqueous media. In these biomineralization processes the organisms use a twofold strategy to control magnetite formation: the mineral is formed from a poorly crystalline precursor phase, and nucleation and growth are controlled through the interaction of the mineral with biomolecular templates and additives. Taking inspiration from this biological strategy is a promising route to achieve control over the kinetics of magnetite crystallization under ambient conditions and in aqueous media. In this review we first summarize the main characteristics of magnetite and what is known about the mechanisms of magnetite biomineralization. We then describe the most common routes to synthesize magnetite and subsequently will introduce recent efforts in bioinspired magnetite synthesis. We describe how the use of poorly ordered, more soluble precursors such as ferrihydrite (FeH) or white rust (Fe(OH)2) can be employed to control the solution supersaturation, setting the conditions for continued growth. Further, we show how the use of various organic additives such as proteins, peptides and polymers allows for either the promotion or inhibition of magnetite nucleation and growth processes. At last we discuss how the formation of magnetite-based organic-inorganic hybrids leads to new functional nanomaterials. PMID- 27385628 TI - Self-Assembled Heterojunction Carbon Nanotubes Synergizing with Photoimmobilized IGF-1 Inhibit Cellular Senescence. AB - Synthesis of artificial and functional structures for bone tissue engineering has been well recognized but the associated cell senescence issue remains much less concerned so far. In this work, surface-modified polycaprolactone-polylactic acid scaffolds using self-assembled heterojunction carbon nanotubes (sh-CNTs) combined with insulin-like growth factor-1 are synthesized and a series of structural and biological characterizations are carried out, with particular attention to cell senescence mechanism. It is revealed that the modified scaffolds can up-regulate the expressions of alkaline phosphates and bone morphogenetic proteins while down regulate the expressions of senescence-related proteins in mesenchymal stem cells, demonstrating the highly preferred anti-senescence functionality of the sh CNTs modified scaffolds in bone tissue engineering. Furthermore, it is also found that with sh-CNTs, scaffolds can accelerate bone healing with extremely low toxicity in vivo. PMID- 27385629 TI - Thrombotic Events in Asymptomatic FXII Deficiency versus Symptomatic FXI Deficiency: Surprising Observations. AB - OBJECTIVE: To evaluate the impact of an asymptomatic congenital clotting defect (FXII deficiency) versus that of a similar but symptomatic defect (FXI deficiency) on protection from thrombosis. PATIENTS AND METHODS: All patients with FXII or FXI deficiency and thrombosis were gathered from a time-unlimited PubMed search that was carried out twice and from personal records. Combined defects were excluded. The defect had to be proven by the demonstration of a suited hereditary pattern and by a specific clotting assay. Only patients with a factor activity level of <30% of normal were selected. RESULTS: Twenty-eight patients with an FXII deficiency presented with arterial thrombosis, mainly myocardial infarction, and 29 showed venous thrombosis; for FXI deficiency, these figures were 43 and 10, respectively. The ratio of arterial and venous thrombosis was 0.96 and 4.3, respectively, for FXII and FXI deficiency. CONCLUSIONS: Factor FXII deficiency supplies no protection from arterial or venous thrombosis. FXI deficiency shows no protection from arterial thrombosis but appears to guarantee protection from venous thrombosis. A symptomatic, namely bleeding, condition (FXI deficiency) provides protection from venous thrombosis whereas an asymptomatic one (FXII deficiency) does not. PMID- 27385630 TI - In vitro evaluation of the mutagenic and cytostatic effect of Tamaron, Lannate and Manzate alone and in mixture. AB - Pesticides are often used in agriculture, especially in floriculture. They are frequently applied in binary or ternary mixtures. Nevertheless, their impact on the genetic material has been scarcely explored. In this study, the mutagenic and cytostatic effect of three widely used pesticides, alone and combined, were analyzed. Briefly, lymphocytes cultures were obtained from peripheral blood samples of five healthy donors to determine the sister chromatid exchange and the replicative index (RI). Then, lymphocytes were exposed to Tamaron (100 ppm), Lannate (200 ppm) and Manzate (300 ppm) alone and combined. For the binary mixtures, the concentrations used were 50 ppm of Tamaron, 100 ppm of Lannate and 150 ppm of Manzate. For the ternary mixtures the following concentrations were used: Tamaron (33 ppm), Lannate (70 ppm) and Manzate (100 ppm). Finally, differential staining was performed. It was found that the frequency of SCE/cell showed a significant difference (P <= 0.05) between the control (2.66) and the individual treatments of Tamaron (4.87), Lannate: (5.12) and Manzate (4.23). Also, the values of the SCE in the binary mixture of Tamaron+Lannate (5.57), Tamaron+Manzate (6.06) and Lannate+Manzate (6.22) and the ternary mixture (6.63) were statistically different compared to the control. In the RI there was a significant difference between the control (1.98) and the Manzate (1.87). RI differences were also statistically significant (P <= 0.05) in mixtures of Tamaron+Lannate (1.64), Tamaron+Manzate (1.63), Lannate+Manzate (1.69) and total mixture (1.53). Therefore, it is suggested that these pesticides alone and in mixtures have both mutagenic and cytostatic synergistic effect in human lymphocytes in vitro. PMID- 27385632 TI - Annulation of Alkynyl Aryl Ethers with Allyl Pivalates To Give 2,3 Bismethylenechromanes through Double C-H Bond Cleavage. AB - The treatment of silylethynyloxyarenes with allylic pivalates in the presence of a palladium catalyst led to efficient C-H bond cleavage in both substrates and a novel annulation reaction to give 2,3-bismethylenechromanes. When ortho-allylated silylethynyloxybenzenes were used as the substrates, the same products were obtained. This result shows that site-selective intramolecular hydrovinylation is involved in the annulation reaction. The synthetic utility of the products was demonstrated by the construction of condensed polycycles. PMID- 27385633 TI - Sensitive proton-detected solid-state NMR spectroscopy of large proteins with selective CH3 labelling: application to the 50S ribosome subunit. AB - Solid-state NMR spectroscopy allows the characterization of the structure, interactions and dynamics of insoluble and/or very large proteins. Sensitivity and resolution are often major challenges for obtaining atomic-resolution information, in particular for very large protein complexes. Here we show that the use of deuterated, specifically CH3-labelled proteins result in significant sensitivity gains compared to previously employed CHD2 labelling, while line widths increase only marginally. We apply this labelling strategy to a 468 kDa large dodecameric aminopeptidase, TET2, and the 1.6 MDa-large 50S ribosome subunit of Thermus thermophilus. PMID- 27385634 TI - Effect of Peptide Sequences on Supramolecular Interactions of Naphthaleneimide/Tripeptide Conjugates. AB - In this study, we reported a significant difference in the supramolecular hydrogelation of newly discovered NI-GFF (NI-Gly-l-Phe-l-Phe) and NI-FFG (NI-l Phe-l-Phe-Gly) on the basis of their phase diagrams. With a small difference in the peptide chain between NI-GFF and NI-FFG, we observed a significant difference in their self-assembly properties; NI-GFF formed a stable gel at neutral pH, whereas NI-FFG did not, under the same conditions. From spectroscopic and computational studies, intermolecular pi-pi interactions and extended hydrogen bonding interactions might reinforce the intermolecular interactions of NI-GFF, which may facilitate the formation of the self-assembled nanostructures and the hydrogel. In addition, the aggregation-induced emission (AIE)-active NI-GFF reveals relatively good biocompatibility compared with that of NI-FFG for two commonly used cell lines, suggesting that it is a promising candidate for use as a supramolecular material in biomedical applications. Our results highlight the importance of tripeptide sequences in a self-assembling hydrogel system. PMID- 27385635 TI - Collaborative goal setting with and for children as part of therapeutic intervention. AB - PURPOSE: This study explored collaborative goal setting with children, parents, and teachers, and children's reasons for their goals based on their perceived self-efficacy, using the Austrian-German Perceived Efficacy and Goal Setting System (AG-PEGS). METHOD: Thirty-eight children from age 5 to 10 years (referred to occupational therapists because of difficulties in performing everyday activities), their parents and teachers participated in this mixed methods study. Participants' goals were analyzed using descriptive statistics and content analysis. Data were grouped into thematic categories, and attributed to health factors according to the International Classification of Functioning, Disability, and Health-Children & Youth Version (ICF-CY). RESULTS: Children's responses underlined the significance of self-efficacy and participation for a child's health and well-being. They gave priority to their independence, competence, and joy in meaningful everyday activities and indicated social motives such as belonging to and being accepted by others for their mainly participation-oriented goals. Parents' main concerns were related to school task performance, whereas teachers mainly chose body functions and school activities to be the focus of occupational therapy intervention. CONCLUSIONS: Exploring clients' priorities, the meanings they attributed to activities in daily life, and their underlying motives for goals should be part of therapeutic intervention. Children and their caregivers are valid and important sources for therapeutic goal setting. Basic human needs, e.g., for relatedness, competence (self-efficacy), autonomy, and meaningful personal orientation, should be considered when prioritizing goals for intervention. Implications for Rehabilitation Children are a valid and important source for therapeutic goal setting. Children's goals focused on activities and participation in all life areas, and half of the parents' goals on activities as relevant for productivity (followed by self-care and leisure), while teachers tended to prioritize goals at the body functions and structures level. The experience of their task performance affecting participation, and the basic needs for independence, relatedness (belonging to and being accepted by others), competence (self-efficacy), and joy through engagement in personally meaningful activities are main motives for children with developmental disabilities to choose their goals for intervention. A client-centred approach in working with children with developmental disabilities requires time and attention for exploring meaning-attributed activities for children and their proxies when collaboratively setting goals. PMID- 27385636 TI - Amide proton transfer imaging of brain tumors using a self-corrected 3D fast spin echo dixon method: Comparison With separate B0 correction. AB - PURPOSE: To assess the quantitative performance of three-dimensional (3D) fast spin-echo (FSE) Dixon amide proton transfer (APT) imaging of brain tumors compared with B0 correction with separate mapping methods. METHODS: Twenty-two patients with brain tumors (54.2 +/- 18.7 years old, 12 males and 10 females) were scanned at 3 Tesla (T). Z-spectra were obtained at seven different frequency offsets at +/-3.1 ppm, +/- 3.5 ppm, +/- 3.9 ppm, and -1560 ppm. The scan was repeated three times at +3.5 ppm with echo shifts for Dixon B0 mapping. The APT image corrected by a three-point Dixon-type B0 map from the same scan (3D-Dixon) or a separate B0 map (2D-separate and 3D-separate), and an uncorrected APT image (3D-uncorrected) were generated. We compared the APT-weighted signals within a tumor obtained with each 3D method with those obtained with 2D-separate as a reference standard. RESULTS: Excellent agreements and correlations with the 2D separate were obtained by the 3D-Dixon method for both mean (ICC = 0.964, r = 0.93, P < 0.0001) and 90th-percentile (ICC = 0.972, r = 0.95, P < 0.0001) APT weighted signals. These agreements and correlations for 3D-Dixon were better than those obtained by the 3D-uncorrected and 3D-separate methods. CONCLUSION: The 3D FSE Dixon APT method with intrinsic B0 correction offers a quantitative performance that is similar to that of established two-dimensional (2D) methods. Magn Reson Med 77:2272-2279, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27385637 TI - Experimental and molecular docking investigation on DNA interaction of N substituted phthalimides: antibacterial, antioxidant and hemolytic activities. AB - A series of Schiff base molecules derived from a phthalimide scaffold was investigated as efficient antibacterial, antioxidant and DNA-interacting agents. The spectroscopic characterization of these derivatives was studied in detail using elemental analysis and spectroscopic techniques. The DNA-binding profile of title molecules against Ct-DNA (calf thymus) was investigated by absorbance, fluorescence, hydrodynamics and thermal denaturation investigations. The bacterial inhibition potential of these molecules was investigated against Escherichia coli and Staphylococcus aureus. Molecule 3c emerged as the most active against S. aureus (IC50 : 14.8 MUg/mL), whereas compounds 3a and 3b displayed potential antibacterial activities against E. coli (IC50 : 49.7 and 67.6 MUg/mL). Molecular docking studies of these compounds against GlcN-6-P synthase were carried out to rationalize antibacterial efficiency of these molecules. These newly synthesized molecules were screened for their scavenging capacity against 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and H2 O2 free radicals and the results were compared with ascorbic acid as synthetic antioxidant. The title molecules 3a, 3b and 3e showed less than 20% hemolysis, which indicated their significant non-toxic behavior. PMID- 27385638 TI - Magnetotransport and magnetothermal properties of the ternary intermetallic compound TbFe2Al10. AB - We have studied the temperature and field dependences of electrical resistivity and heat capacity of TbFe2Al10, and have also complimented the above studies with low field magnetization measurements. In zero magnetic field, TbFe2Al10 exhibits paramagnetic (PM) to ferrimagnetic (Ferri-I) and Ferri-I to antiferromagnetic (AFM) phase transitions below 17.6 and 10 K respectively. We have found that the electrical resistivity of TbFe2Al10 exhibits a sharp rise across the PM to Ferri I phase transition in this compound. Our analysis indicates that this sharp rise of electrical resistivity is related to the formation of new zone boundaries (across the PM to Ferri-I phase transition) that reduce the area of the Fermi surface. We have found that TbFe2Al10 exhibits large magnetoresistance (MR) below 100 K. Overall, the MR behaviour of TbFe2Al10 below 17.6 K in different magnetic fields reveals strong competition between AFM and ferromagnetic (FM) correlations, which seems to be quite intrinsic to the magnetic structure of the compound. Our analysis indicates that the large MR and magnetocaloric effect persisting deep inside the PM regime of TbFe2Al10 is mainly related to the presence of FM spin fluctuations and the formation of a Griffiths like (GL) phase consisting of FM clusters within the PM regime. The formation of the GL phase may be mediated by the static crystal defects in the midst of the competing inter and intra layer magnetic interactions. PMID- 27385639 TI - EcoTILLING revealed SNPs in GhSus genes that are associated with fiber- and seed related traits in upland cotton. AB - Cotton is the most important textile crop in the world due to its cellulose enriched fibers. Sucrose synthase genes (Sus) play pivotal roles in cotton fiber and seed development. To mine and pyramid more favorable alleles for cotton molecular breeding, single nucleotide polymorphisms (SNPs) of GhSus family genes were investigated across 277 upland cotton accessions by EcoTILLING. As a result, a total of 24 SNPs in the amplified regions of eight GhSus genes were identified. These SNPs were significantly associated with at least one fiber- or seed-related trait measured in Nanjing, Anyang and Kuche in 2007-2009. Four main-effect quantitative trait nucleotides (QTNs) and five epistatic QTNs, with 0.76-3.56% of phenotypic variances explained by each QTN (PVE), were found to be associated with yield-related traits; six epistatic QTNs, with the 0.43-3.48% PVE, were found to be associated with fiber quality-related traits; and one main-effect QTN and one epistatic QTN, with the PVE of 1.96% and 2.53%, were found to be associated with seed oil content and protein content, respectively. Therefore, this study provides new information for molecular breeding in cotton. PMID- 27385640 TI - Peptide Synthesis on a Next-Generation DNA Sequencing Platform. AB - Methods for displaying large numbers of peptides on solid surfaces are essential for high-throughput characterization of peptide function and binding properties. Here we describe a method for converting the >10(7) flow cell-bound clusters of identical DNA strands generated by the Illumina DNA sequencing technology into clusters of complementary RNA, and subsequently peptide clusters. We modified the flow-cell-bound primers with ribonucleotides thus enabling them to be used by poliovirus polymerase 3D(pol) . The primers hybridize to the clustered DNA thus leading to RNA clusters. The RNAs fold into functional protein- or small molecule binding aptamers. We used the mRNA-display approach to synthesize flow-cell tethered peptides from these RNA clusters. The peptides showed selective binding to cognate antibodies. The methods described here provide an approach for using DNA clusters to template peptide synthesis on an Illumina flow cell, thus providing new opportunities for massively parallel peptide-based assays. PMID- 27385641 TI - Control of Electronic Structures and Phonon Dynamics in Quantum Dot Superlattices by Manipulation of Interior Nanospace. AB - Quantum dot (QD) superlattices, periodically ordered array structures of QDs, are expected to provide novel photo-optical functions due to their resonant couplings between adjacent QDs. Here, we computationally demonstrated that electronic structures and phonon dynamics of a QD superlattice can be effectively and selectively controlled by manipulating its interior nanospace, where quantum resonance between neighboring QDs appears, rather than by changing component QD size, shape, compositions, etc. A simple H-passivated Si QD was examined to constitute one-, two-, and three-dimensional QD superlattices, and thermally fluctuating band energies and phonon modes were simulated by finite-temperature ab initio molecular dynamics (MD) simulations. The QD superlattice exhibited a decrease in the band gap energy enhanced by thermal modulations and also exhibited selective extraction of charge carriers out of the component QD, indicating its advantage as a promising platform for implementation in solar cells. Our dynamical phonon analyses based on the ab initio MD simulations revealed that THz-frequency phonon modes were created by an inter-QD crystalline lattice formed in the QD superlattice, which can contribute to low energy thermoelectric conversion and will be useful for direct observation of the dimension-dependent superlattice. Further, we found that crystalline and ligand originated phonon modes inside each component QD can be independently controlled by asymmetry of the superlattice and by restriction of the interior nanospace, respectively. Taking into account the thermal effects at the finite temperature, we proposed guiding principles for designing efficient and space-saving QD superlattices to develop functional photovoltaic and thermoelectric devices. PMID- 27385642 TI - Dimer/monomer status and in vivo function of salt-bridge mutants of the plant UV B photoreceptor UVR8. AB - UV RESISTANCE LOCUS8 (UVR8) is a photoreceptor for ultraviolet-B (UV-B) light that initiates photomorphogenic responses in plants. UV-B photoreception causes rapid dissociation of dimeric UVR8 into monomers that interact with CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1) to initiate signal transduction. Experiments with purified UVR8 show that the dimer is maintained by salt-bridge interactions between specific charged amino acids across the dimer interface. However, little is known about the importance of these charged amino acids in determining dimer/monomer status and UVR8 function in plants. Here we evaluate the use of different methods to examine dimer/monomer status of UVR8 and show that mutations of several salt-bridge amino acids affect dimer/monomer status, interaction with COP1 and photoreceptor function of UVR8 in vivo. In particular, the salt-bridges formed between arginine 286 and aspartates 96 and 107 are key to dimer formation. Mutation of arginine 286 to alanine impairs dimer formation, interaction with COP1 and function in vivo, whereas mutation to lysine gives a weakened dimer that is functional in vivo, indicating the importance of the positive charge of the arginine/lysine residue for dimer formation. Notably, a UVR8 mutant in which aspartates 96 and 107 are conservatively mutated to asparagine is strongly impaired in dimer formation but mediates UV-B responses in vivo with a similar dose-response relationship to wild-type. The UV-B responsiveness of this mutant does not correlate with dimer formation and monomerisation, indicating that monomeric UVR8 has the potential for UV-B photoreception, initiating signal transduction and responses in plants. PMID- 27385643 TI - Quality of initial HIV care in Canada: extension of a composite programmatic assessment tool for HIV therapy. AB - OBJECTIVES: To document the quality of initial HIV care in Canada using the Programmatic Compliance Score (PCS), to explore the association of the PCS with mortality, and to identify factors associated with higher quality of care. METHODS: We analysed data from the Canadian Observational Cohort Collaboration (CANOC), a multisite Canadian cohort of HIV-positive adults initiating combination antiretroviral therapy (ART) from 2000 to 2011. PCS indicators of noncompliance with HIV treatment guidelines include: fewer than three CD4 count tests in the first year of ART; fewer than three viral load tests in the first year of ART; no drug resistance testing before initiation; baseline CD4 count < 200 cells/mm3 ; starting a nonrecommended ART regimen; and not achieving viral suppression within 6 months of initiation. Indicators are summed for a score from 0 to 6; higher scores indicate poorer care. Cox regression was used to assess the association between PCS and mortality and ordinal logistic regression was used to explore factors associated with higher quality of care. RESULTS: Of the 7460 participants (18% female), the median score was 1.0 (Q1-Q3 1.0-2.0); 21% scored 0 and 8% scored >= 4. In multivariable analysis, compared with a score of 0, poorer PCS was associated with mortality for scores > 1 [score = 2: adjusted hazard ratio (AHR) 1.64; 95% confidence interval (CI) 1.13-2.36; score = 3: AHR 2.02; 95% CI 1.38-2.97; score >= 4: AHR 2.14; 95% CI 1.43-3.21], after adjustments for age, sex, province, ART start year, hepatitis C virus (HCV) coinfection, and baseline viral load. Women, individuals with HCV coinfection, younger people, and individuals starting ART earlier (2000-2003) had poorer scores. CONCLUSIONS: Our findings further validate the PCS as a predictor of all-cause mortality. Disparities identified suggest that further efforts are needed to ensure that care is equitably accessible. PMID- 27385644 TI - Renal cellular hypoxia in adenine-induced chronic kidney disease. AB - We determined whether adenine-induced chronic kidney disease (CKD) in rats is associated with renal tissue hypoxia. Adenine (100 mg) or its vehicle was administered to male Sprague-Dawley rats, daily by oral gavage, over a 15-day period. Renal function was assessed before, and 7 and 14 days after, adenine treatment commenced, by collection of a 24-hour urine sample and a blood sample from the tail vein. On day 15, arterial pressure was measured in conscious rats via the tail artery. Renal tissue hypoxia was then assessed by pimonidazole adduct immunohistochemistry and fibrosis was assessed by staining tissue with picrosirius red and Masson's trichrome. CKD was evident within 7 days of commencing adenine treatment, as demonstrated by increased urinary albumin to creatinine ratio (30 +/- 12-fold). By day 14 of adenine treatment plasma creatinine concentration was more than 7-fold greater, and plasma urea more than 5-fold greater, than their baseline levels. On day 15, adenine-treated rats had slightly elevated mean arterial pressure (8 mmHg), anaemia and renomegaly. Kidneys of adenine-treated rats were characterised by the presence of tubular casts, dilated tubules, expansion of the interstitial space, accumulation of collagen, and tubulointerstitial hypoxia. Pimonidazole staining (hypoxia) co localised with fibrosis and was present in both patent and occluded tubules. We conclude that renal tissue hypoxia develops rapidly in adenine-induced CKD. This model, therefore, should prove useful for examination of the temporal and spatial relationships between tubulointerstitial hypoxia and the development of CKD, and thus the testing of the 'chronic hypoxia hypothesis'. PMID- 27385645 TI - A single-centre study of haemostatic outcomes of joint replacement in von Willebrand disease and control patients and an analysis of the literature. AB - INTRODUCTION: Haemostatic assessments of patients with von Willebrand disease (VWD) who undergo total knee arthroplasty (TKA) and total hip arthroplasty (THA) have mainly relied on subjective parameters. AIMS: To compare objective haemostatic outcomes of TKA/THA in VWD patients and controls without bleeding disorders. METHODS: We retrospectively analysed haemostatic outcomes in VWD patients undergoing TKA/THA from 1993 to 2011 and compared them with two matched controls per operation. Using one-way analysis of variance, we tested the effect of VWD on bleeding risk after TKA and THA. RESULTS: Twelve VWD patients (6 type 1, 3 type 2M, 1 each of types 2A/2B/3) undergoing 19 operations (12 TKA, 7 THA) were matched to 38 controls. One (5%) of 19 operations in VWD patients and none of the control operations met clinical criteria for major bleeding. Baseline and postoperative day 1 haemoglobin levels, postoperative blood loss, transfused red blood cells (RBCs) and mean hospitalization days were not significantly different. More VWD patients than controls received RBC transfusions [12 (63%) vs. 12 (32%)]. Only 9 (47%) VWD patients vs. 38 (100%) controls received pharmacologic VTE prophylaxis. No postoperative symptomatic VTE occurred in either group. CONCLUSION: In this largest, single-institutional study, von Willebrand factor replacement based on daily levels resulted in low frequency of major bleeding in VWD patients after TKA/THA. RBC transfusion was more frequent compared with matched controls, but other objective measures of haemostasis were similar. Lack of sufficient details in published reports precluded comparison of haemostatic outcomes. PMID- 27385646 TI - Low transfusion transmission of hepatitis E among 25,637 single-donation, nucleic acid-tested blood donors. AB - BACKGROUND: Hepatitis E virus genotype-3 (HEV-gt-3) causes autochthonous infections in western countries, with a primary reservoir in animals, especially pigs. HEV transfusion transmission has been reported, and HEV-gt-3 prevalence is high in some European countries. The prevalence of HEV RNA was investigated among Danish blood donors, and the prevalence of HEV transfusion-transmitted infection (TTI) was investigated among recipients. STUDY DESIGN AND METHODS: Samples from 25,637 consenting donors collected during 1 month in 2015 were screened retrospectively using an individual-donation HEV RNA nucleic acid test with a 95% detection probability of 7.9 IU/mL. HEV-positive samples were quantified by real time polymerase chain reaction and genotyped. Transmission was evaluated among recipients of HEV RNA-positive blood components. Phylogenetic analyses compared HEV sequences from blood donors, symptomatic patients, and swine. RESULTS: Eleven donations (0.04%) were confirmed as positive for HEV RNA (median HEV RNA level, 13 IU/mL). Two donations were successfully genotyped as HEV-gt-3. Only one donor had a travel history outside Europe. Nine of 11 donors were male, but the gender ratio was nonsignificant compared with the total donor population. Seven available recipients tested negative for HEV RNA and anti-HEV immunoglobulin M in follow-up samples. One recipient was HEV RNA-negative but anti-HEV immunoglobulin G-positive. HEV TTI was considered unlikely, but a transfusion-induced secondary immune response could not be excluded. Phylogenetic analysis showed relatively large sequence differences between HEV from donors, symptomatic patients, and swine. CONCLUSIONS: Despite an HEV RNA prevalence of 0.04% in Danish blood donations, all HEV-positive donations carried low viral loads, and no evidence of TTI was found. PMID- 27385647 TI - Domestic dog exposure at birth reduces the incidence of atopic dermatitis. AB - BACKGROUND: While the etiopathogenesis of atopic dermatitis is complex and poorly understood, neonatal exposures are important for disease occurrence. However, the effect of dog exposure on the risk of atopic dermatitis is unresolved. OBJECTIVE: We investigated whether domestic dog exposure affected the risk of atopic dermatitis in children during the first 3 years of life. METHODS: Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) are ongoing prospective clinical birth cohort studies. Data from 411 children born to mothers with asthma (COPSAC2000 ) and 700 unselected children (COPSAC2010 ) were analyzed following the same protocols at the same research site. Atopic dermatitis was diagnosed prospectively according to the Hanifin-Rajka criteria. Parental history of asthma, eczema, or rhinitis was defined by self-reported physician diagnosis. In the COPSAC2000 , maternal specific serum IgE against eight inhalant allergens was sampled after the children's birth and at pregnancy week 24 in the COPSAC2010 cohort. Associations between dog exposure and atopic dermatitis were analyzed by Cox proportional hazard regression models and adjusted for lifestyle confounders. RESULTS: In the COPSAC2000 and COPSAC2010 cohorts, the risk of atopic dermatitis was significantly lower in children with domestic dog exposure (adjusted HR = 0.46 [0.25-0.87], P = 0.02; and adjusted HR = 0.58 [0.36-0.93], P = 0.03, respectively). The risk of atopic dermatitis decreased in a dose-dependent manner with increasing number of dogs (adjusted HR = 0.58 [0.38-0.89], P = 0.01) in the COPSAC2010 . The protective effect was restricted to children born to mothers with atopic disease in the unselected COPSAC2010 cohort (adjusted HR = 0.39 [0.19 0.82], P = 0.01), as no effect was observed in children born to mothers without atopic disease (adjusted HR = 0.92 [0.49-1.73], P = 0.79). Paternal atopic status did not affect the risk of atopic dermatitis. We found no significant interaction between the CD14 T/T genotype and domestic dog exposure in either cohort (COPSAC2000 , P = 0.36; and COPSAC2010 cohort, P = 0.42). CONCLUSION: Neonatal domestic dog exposure was associated with a strongly reduced risk of atopic dermatitis in two independent birth cohorts and in a dose-dependent manner. While the mechanisms involved are unclear, our findings raise the question of whether in utero exposures may affect the risk of atopic dermatitis and emphasize the importance of the early environment for disease trajectory. PMID- 27385648 TI - Discrimination, HIV among People Who Use Drugs, and the UNGASS 2016 on the World Drug Problem. PMID- 27385649 TI - A Ni(iii) complex stabilized by silica nanoparticles as an efficient nanoheterogeneous catalyst for oxidative C-H fluoroalkylation. AB - We have developed Ni(III)-doped silica nanoparticles ([(bpy)xNi(III)]@SiO2) as a recyclable, low-leaching, and efficient oxidative functionalization nanocatalyst for aromatic C-H bonds. The catalyst is obtained by doping the complex [(bpy)3Ni(II)] on silica nanoparticles along with its subsequent electrooxidation to [(bpy)xNi(III)] without an additional oxidant. The coupling reaction of arenes with perfluoroheptanoic acid occurs with 100% conversion of reactants in a single step at room temperature under nanoheterogeneous conditions. The catalyst content is only 1% with respect to the substrates under electrochemical regeneration conditions. The catalyst can be easily separated from the reaction mixture and reused a minimum of five times. The results emphasize immobilization on the silica support and the electrochemical regeneration of Ni(III) complexes as a facile route for developing an efficient nanocatalyst for oxidative functionalization. PMID- 27385650 TI - Bilateral vagal automatic periodic stimulation in single-incision transaxillary robotic total thyroidectomy. PMID- 27385651 TI - A Versatile and Clearable Nanocarbon Theranostic Based on Carbon Dots and Gadolinium Metallofullerene Nanocrystals. AB - Nanocarbons such as carbon nanotubes, graphene derivatives, and carbon nanohorns have illustrated their potential uses as cancer theranostics owing to their intrinsic fluorescence or NIR absorbance as well as superior cargo loading capacity. However, some problems still need to be addressed, such as the fates and long-term toxicology of different nanocarbons in vivo and the improvement of their performance in various biomedical imaging-guided cancer therapy systems. Herein, a versatile and clearable nanocarbon theranostic based on carbon dots (CDs) and gadolinium metallofullerene nanocrystals (GFNCs) is first developed, in which GFNCs enhance the tumor accumulation of CDs, and CDs enhance the relaxivity of GFNCs, leading to an efficient multimodal imaging-guided photodynamic therapy in vivo without obvious long-term toxicity. Furthermore, biochemical analysis reveals that the novel nanotheranostic can harmlessly eliminate from the body in a reasonable period of time after exerting diagnostic and therapeutic function. PMID- 27385652 TI - Structured Exercise in Obese Diabetic Patients with Chronic Kidney Disease: A Randomized Controlled Trial. AB - BACKGROUND: Patients with type 2 diabetes mellitus (DM), obesity, and chronic kidney disease (CKD) are generally physically inactive and may benefit from exercise. Our objective was to determine the effects of structured exercise on physical fitness, kidney function, endothelial function, inflammation, and body composition in such patients. METHODS: In this randomized, controlled trial, 36 male patients (age 49-81) were randomly assigned to exercise + diet management (n = 18) or diet alone (n = 18). Participants were eligible if they had type 2 DM, body mass index >30 kg/m2, CKD stages 2-4, and persistent proteinuria (>200 mg/g creatinine for >3 months). The exercise intervention was a 12-week (3 days per week) program of aerobic and resistance training followed by 40 weeks of home exercise. The primary outcome measure was change from baseline in urine protein to creatinine ratio (UPCR) at 12 and 52 weeks. RESULTS: Thirty-two participants completed the study (14 exercise + diet, 18 diet-alone group). The change from baseline in UPCR was slightly greater in the diet-alone group at 12 weeks but not at 52 weeks. Changes in both symptom-limited and constant-workrate treadmill times were significantly higher in the exercise + diet group at 12 weeks but not at 52 weeks. There were no significant differences in urine albumin to creatinine ratio, estimated glomerular filtration rate, endothelial function, inflammation, or body composition between the groups. CONCLUSIONS: In obese diabetic subjects with CKD, structured exercise improved exercise capacity but not body composition or renal function. This is a work of the US Government and is not subject to copyright protection in the USA. Foreign copyrights may apply. Published by S. Karger AG, Basel. PMID- 27385653 TI - Progressive Abdominal Pain Following Laparoscopic Cholecystectomy. PMID- 27385654 TI - Fragment-Based Discovery of Dual JC Virus and BK Virus Helicase Inhibitors. AB - There are currently no treatments for life-threatening infections caused by human polyomaviruses JCV and BKV. We therefore report herein the first crystal structure of the hexameric helicase of JCV large T antigen (apo) and its use to drive the structure-based design of dual JCV and BKV ATP-competitive inhibitors. The crystal structures obtained by soaking our early inhibitors into the JCV helicase allowed us to rapidly improve the biochemical activity of our inhibitors from 18 MUM for the early 6-(2-methoxyphenyl)- and the 6-(2-ethoxyphenyl) [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole hits 1a and 1b to 0.6 MUM for triazolopyridine 12i. In addition, we were able to demonstrate measurable antiviral activity in Vero cells for our thiazolopyridine series in the absence of marked cytotoxicity, thus confirming the usefulness of this approach. PMID- 27385655 TI - Simultaneous gas chromatographic determination of chlorpyrifos and its impurity sulfotep in liquid pesticide formulations. AB - An analytical method for simultaneous determination of the active substance (chlorpyrifos) and its relevant impurity (sulfotep) in commercial pesticide formulations has been developed and validated. The proposed method entails extraction of the analytes from samples by sonication with acetone and analysis by gas chromatography-flame ionization detection (GC-FID). The proposed method was characterized by satisfactory accuracy and precision. The repeatability expressed as relative standard deviation (RSD) was lower than the acceptable values calculated from the modified Horwitz equation whereas individual recoveries were in the range of 98-102% and 80-120% for chlorpyrifos and sulfotep, respectively. The limit of quantification (LOQ) for the impurity (sulfotep) was 0.003 mg mL(-1) corresponding to the maximum permitted level according to Food and Agricultural Organization of the United Nations (FAO) specifications for the active substance (chlorpyrifos) being 3 g kg(-1) of the chlorpyrifos content found. The main advantage of the proposed method was a considerable reduction in the analysis time since both analytes were determined based on a single injection into the GC-FID. Analysis of real samples of commercial pesticide formulations confirmed fitness-for-purpose of the proposed method. PMID- 27385656 TI - Evaluation of the clinical utility of the Home Falls and Accidents Screening Tool (HOME FAST). AB - PURPOSE: The HOME FAST was developed and trialled in Australia as a screening tool designed to be used by any health professional to identify older people at increased risk of falls and to facilitate referral for more detailed assessment and intervention. This study aimed to evaluate the clinical utility of the HOME FAST from the perspective of users. METHOD: A mixed-methods approach using survey data (n = 32), focus group data (n = 46) and interview data (n = 5) from occupational therapists, physiotherapists, community nurses and other health professionals working in hospitals, community services and private practice, located in the UK, Canada and Australia. Data were integrated using a matrix of quantitative and qualitative data that aligned the findings with established theoretical constructs of clinical utility. RESULTS: Findings across the data sources provide evidence of the clinical utility of the HOME FAST, and these findings align with theoretical constructs about how a tool such as the HOME FAST is adopted in practice. CONCLUSION: The HOME FAST can be used in a variety of international setting in developed countries and by different health professionals as a screening tool. A manual would assist in the consistent application of the HOME FAST. Implications for Rehabilitation Hazards in the home environment are a key contributor to falls risk for older people The Home Falls and Accidents Screening Tool (HOME FAST) was designed for any health professional to screen older people at increased risk of falling because of home hazards. Even with psychometric evidence of the reliability and validity of a tool, it is critical that the tool can be easily adopted by clinicians (clinical utility), otherwise its applicability to practice and research is limited. An international mixed-method study has provided evidence of the clinical utility of the HOME FAST. PMID- 27385657 TI - A simple procedure for the production of large ferromagnetic cobalt nanoparticles. AB - Epsilon cobalt (epsilon-Co) nanoparticles in a number of octahedral morphologies have been synthesised. The particles are polycrystalline, with sizes in the order of 30 nm. Magnetic studies reveal the particles are ferromagnetic, with a room temperature saturation magnetisation of 131 emu g(-1). Unlike other large cubic epsilon-Co syntheses, we have not added an additional co-surfactant. Instead, we have modified the heating regime and reaction agitation. This alternative method highlights the complex chemistry associated with the formation of cobalt nanoparticles by thermal decomposition. PMID- 27385658 TI - Vestibular migraine screening in a migraine-diagnosed patient population, and assessment of vestibulocochlear function. AB - OBJECTIVE: The primary aim of this study is to do a vestibular migraine scan in a population of patients with migraine diagnosis using the most recent standardized diagnosis criterion which is International Classification of Headache Disorders (ICHD) 3 Beta and to identify the epidemiological data. The second part of the study involves performing several vestibulocochlear tests on patients who received vestibular migraine (VM) diagnosis to collect data that may be important for diagnostic purposes by comparing the patients with normal population when necessary. DESIGN: Blind, cross-sectional study. SETTING: Tertiary referral hospital. PARTICIPANTS: One hundred patients were scanned for VM using ICHD 3 Beta guideline. MAIN OUTCOME MEASURES: In order to evaluate the vestibulocochlear functions of the patients with VM diagnosis, audiometry, tympanometry, electrocochleography (EcochG), computerized dynamic posturography (CDP) and video head impulse test (vHIT) were performed; besides in order to evaluate the significance of the results of the tests, second group was formed with migraine patients without any vestibular complaints and control group was formed from healthy population when needed. RESULTS: VM prevalence was determined to be 21% in migraine patients which is much higher than stated in current literature. No significant difference was observed between migraine and VM patients with respect to audiometric and tympanometric measurements. According to the CDP results, balance defects were present in VM patients, even during attack-free periods. EcochG data suggests average SP/AP scores of VM patients are significantly higher than migraine patients. Furthermore, the number of patients who exceeded a limit value of 0.4 or 0.5 in SP/AP scores was significantly higher in VM patients than in migraine patients. Also vHIT results show that nearly half the VM patients, which is a significant ratio, have saccadic movements and this is thought to be compatible with peripheral vestibular involvement. CONCLUSION: Our results suggest VM disease is more common than previously thought. We believe that further EcochG-based studies would shed light on the controversial topic on the intersection and disjunction sets of MD and VM diseases. Although the results of the present study are compatible with peripheral vestibular effects, it is not possible to rule out another central mechanism at some other level. PMID- 27385659 TI - Refugee child oral health. AB - The number of people forced to flee their homes and move around the world is increasing rapidly. Such refugee populations are not only more likely to have poor physical, mental and social health outcomes but also to experience difficulties accessing health services in their new country. In particular, children from refugee backgrounds are at increased risk of poor oral health which in time is associated with poor adult oral health and impacts on child health (e.g. growth and development) and well-being. To date, there is little evidence about the nature and extent of their oral health problems nor interventions to improve their oral health status. This article summarises the evidence surrounding the oral health status of children from refugee backgrounds. In addition, a systematic review of the international literature over the past 10 years is presented which identifies interventions to improve the oral health of these vulnerable paediatric populations. Based on this evidence, potential strategies available to dental service providers to optimise provision of responsive dental care are discussed. PMID- 27385660 TI - Father, Though I Am Strong. PMID- 27385662 TI - Uncontrolled blood pressure as an independent risk factor of early impaired left ventricular systolic function in treated hypertension. AB - BACKGROUND: Uncontrolled blood pressure (BP) is commonly observed in patients receiving antihypertensive agents. However, its relationship with early left ventricular (LV) dysfunction has not been elucidated. METHODS: This study enrolled 276 patients with treated hypertension and 85 healthy controls. The 140/90 mm Hg was used to define controlled (HT1 group, n=145) or uncontrolled BP (HT2 group, n=131) according to the concurrent guidelines. LV myocardial function was assessed by two-dimensional speckle tracking imaging, and the circumferential end-systolic wall stress (cESS)-corrected mid-wall fraction shortening (MWFS), systolic longitudinal (epsilonLs-18), circumferential (epsilonCs-18), and radial (epsilonRs-18) strain were measured. RESULTS: Despite similar ejection fraction, the HT1 and HT2 groups displayed an overall reduction in the cESS-corrected MWFS (13.4+/-2.7 vs 11.7+/-1.7 vs 15.5+/-1.2), epsilonLs-18 (15.6+/-2.8 vs 13.0+/-2.2 vs 17.4+/-2.8), epsilonCs-18 (17.3+/-3.4 vs 14.1+/-2.7 vs 18.9+/-3.3), and epsilonRs-18 (18.4+/-4.0 vs 14.8+/-3.1 vs 20.5+/-4.5) %.cm2 /kdyne.10-2 when compared with the control group (all P<.001). The changes were more obvious in the HT2 group, regardless of LV hypertrophy. Reductions in the cESS-corrected MWFS and epsilonLs-18 were seen in 68 (25%) and 52 (19%) patients, respectively. Uncontrolled BP were 4.365 times (95% CI 2.203-8.648, P<.001) and 3.928 times (1.851-8.337, P<.001) more likely to be associated with the changes. CONCLUSIONS: Uncontrolled BP in hypertensive patients is associated with further reduction in LV myocardial function detected by advanced echocardiographic techniques, which cannot be explained by the increase in afterload. It might be regarded as a composite risk factor for earlier and faster development of clinical heart failure, therefore, a simplified treatment target. PMID- 27385661 TI - Atypical Ewing sarcoma breakpoint region 1 fluorescence in-situ hybridization signal patterns in bone and soft tissue tumours: diagnostic experience with 135 cases. AB - AIMS: Recurrent Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangements characterize a select group of bone and soft tissue tumours. In our routine diagnostic practice with fluorescence in-situ hybridization (FISH), we have occasionally observed EWSR1 gene rearrangements in tumours not associated classically with EWSR1 translocations. This study aimed to review our institutional experience of this phenomenon and also to highlight the occurrence of unusual EWSR1 FISH signals (i.e. 5' centromeric region or 3' telomeric region signals) that do not fulfil the published diagnostic criteria for rearrangements. METHODS AND RESULTS: Using an EWSR1 break-apart probe, we performed FISH assays on formalin-fixed paraffin-embedded tissue sections from 135 bone and soft tissue specimens as part of their routine diagnostic work-up. EWSR1 gene rearrangements were identified in 51% of cases, 56% of which also showed an abnormal FISH signal pattern (in addition to classically rearranged signals). However, atypical FISH signals were present in 45% of the non-rearranged cases. In addition, we observed tumours unrelated to those described classically as EWSR1-associated that were technically EWSR1-rearranged in 6% of cases. Borderline levels of rearrangement (affecting 10-30% of lesional cells) were present in an additional 17% of these cases. CONCLUSIONS: While our study confirmed that FISH is a sensitive and specific tool in the diagnosis of EWSR1-associated tumours, atypical FISH signals and classical rearrangement in entities other than EWSR1-associated tumours can occur. Therefore, it is essential that the FISH result not be used as an isolated test, but must be evaluated in the context of clinical features, imaging, pathological and immunohistochemical findings. PMID- 27385663 TI - Selective Deoxygenation of Biomass-Derived Bio-oils within Hydrogen-Modest Environments: A Review and New Insights. AB - Research development of processes for refining bio-oils is becoming increasingly popular. One issue that these processes possess is their high requirement for H2 gas. In response, researchers must develop catalysts that perform deoxygenation while minimizing H2 consumption-selective deoxygenation. Unlike traditional deoxygenation processes, selective deoxygenation reactions and catalysts represent an information gap that, prior to this publication, has yet to be reviewed. This review addresses the gap by providing both a summary of recent research developments and insight into future developments of new catalytic materials. Bifunctional catalysts containing a combination of oxophilicity and an active metal phase appear to be the most beneficial for selective deoxygenation processes in a H2 -modest environment. It is important that catalysts have a supply of disassociated hydrogen, because without such, activity and stability will suffer. The authors recommend to maximize the use of internally available hydrogen in bio-fuel, which may be the only viable approach for deoxygenation if external H2 gas is limited. This would be possible through the development of catalysts that promote both the water-gas-shift and deoxygenation reactions. PMID- 27385665 TI - Podoconiosis in Rural Tanzania. PMID- 27385666 TI - Rapid Progressive Chagasic Myocarditis: A Multifactorial Condition. PMID- 27385664 TI - Patient/Family Education for Newly Diagnosed Pediatric Oncology Patients. AB - There is a paucity of data to support evidence-based practices in the provision of patient/family education in the context of a new childhood cancer diagnosis. Since the majority of children with cancer are treated on pediatric oncology clinical trials, lack of effective patient/family education has the potential to negatively affect both patient and clinical trial outcomes. The Children's Oncology Group Nursing Discipline convened an interprofessional expert panel from within and beyond pediatric oncology to review available and emerging evidence and develop expert consensus recommendations regarding harmonization of patient/family education practices for newly diagnosed pediatric oncology patients across institutions. Five broad principles, with associated recommendations, were identified by the panel, including recognition that (1) in pediatric oncology, patient/family education is family-centered; (2) a diagnosis of childhood cancer is overwhelming and the family needs time to process the diagnosis and develop a plan for managing ongoing life demands before they can successfully learn to care for the child; (3) patient/family education should be an interprofessional endeavor with 3 key areas of focus: (a) diagnosis/treatment, (b) psychosocial coping, and (c) care of the child; (4) patient/family education should occur across the continuum of care; and (5) a supportive environment is necessary to optimize learning. Dissemination and implementation of these recommendations will set the stage for future studies that aim to develop evidence to inform best practices, and ultimately to establish the standard of care for effective patient/family education in pediatric oncology. PMID- 27385667 TI - Disease Priorities in Zambia. PMID- 27385668 TI - In Response. PMID- 27385670 TI - In Response. PMID- 27385669 TI - Direct Dried Stool Sampling on Filter Paper for Molecular Analyses of Cholera. PMID- 27385671 TI - Long-lasting extreme anemia during the therapy of acute lymphoblastic leukemia in a Jehovah's Witness patient. AB - BACKGROUND: The treatment of patients with acute leukemia, who due to their religious beliefs refuse to accept blood transfusion, is a great challenge for hematologists. CASE REPORT: We present a case of acute pre-T-lymphoblastic leukemia in a Jehovah's Witness who did not accept blood transfusion during chemotherapy. Standard induction and consolidation chemotherapy was used (according to the PALG ALL-6 regiment). RESULTS: During consolidation cycles, darbepoietin alfa, intravenous iron, and total parenteral nutrition was administered. Extreme (Hb < 5 g/dL), long-lasting (41 days) anemia was observed with the lowest Hb concentration amounting to 1.3 g/dL (lasting 7 days). CONCLUSION: We believe this to be the lowest Hb value observed, particularly one that persisted for such a long period of time and resulted in the patient surviving without consequences. The patient remains in complete remission for more than 2 years after diagnosis. PMID- 27385672 TI - Mechanoassisted Synthesis of Sulfonated Covalent Organic Frameworks with High Intrinsic Proton Conductivity. AB - It is challenging to introduce pendent sulfonic acid groups into modularly built crystalline porous frameworks for intrinsic proton conduction. Herein, we report the mechanoassisted synthesis of two sulfonated covalent organic frameworks (COFs) possessing one-dimensional nanoporous channels decorated with pendent sulfonic acid groups. These COFs exhibit high intrinsic proton conductivity as high as 3.96 * 10(-2) S cm(-1) with long-term stability at ambient temperature and 97% relative humidity (RH). In addition, they were blended with nonconductive polyvinylidene fluoride (PVDF) affording a series of mixed-matrix membranes (MMMs) with proton conductivity up to 1.58 * 10(-2) S cm(-1) and low activation energy of 0.21 eV suggesting the Grotthuss mechanism for proton conduction. Our study has demonstrated the high intrinsic proton conductivity of COFs shedding lights on their wide applications in proton exchange membranes. PMID- 27385673 TI - Organic Transistor Arrays Integrated with Finger-Powered Microfluidics for Multianalyte Saliva Testing. AB - A compact multianalyte biosensing platform is reported, composed of an organic electrochemical transistor (OECT) microarray integrated with a pumpless "finger powered" microfluidic, for quantitative screening of glucose, lactate, and cholesterol levels. A biofunctionalization method is designed, which provides selectivity towards specific metabolites as well as minimization of any background interference. In addition, a simple method is developed to facilitate multi-analyte sensing and avoid electrical crosstalk between the different transistors by electrically isolating the individual devices. The resulting biosensing platform, verified using human samples, offers the possibility to be used in easy-to-obtain biofluids with low abundance metabolites, such as saliva. Based on our proposed method, other types of enzymatic biosensors can be integrated into the array to achieve multiplexed, noninvasive, personalized point of-care diagnostics. PMID- 27385674 TI - Learning to Like Exercising: Evaluative Conditioning Changes Automatic Evaluations of Exercising and Influences Subsequent Exercising Behavior. AB - This multistudy report used an experimental approach to alter automatic evaluations of exercise (AEE). First, we investigated the plasticity of AEE (study 1). A computerized evaluative conditioning task was developed that altered the AEE of participants in two experimental groups (acquisition of positive/negative associations involving exercising) and a control group (eta2 part. = .11). Second, we examined connections between changes in AEE and subsequent exercise behavior (chosen intensity on a bike ergometer; study 2) in individuals that were placed in groups according to their baseline AEE. Group differences in exercise behavior were detected (eta2 part. = .29). The effect was driven by the performance of the group with preexisting negative AEE that acquired more positive associations. This illustrates the effect of altered AEE on subsequent exercise behavior and the potential of AEE as a target for exercise intervention. PMID- 27385675 TI - Threatening faces fail to guide attention for adults with autistic-like traits. AB - Individuals diagnosed with autistic spectrum conditions often show deficits in processing emotional faces relative to neurotypical peers. However, little is known about whether similar deficits exist in neurotypical individuals who show high-levels of autistic-like traits. To address this question, we compared performance on an attentional blink task in a large sample of adults who showed low- or high-levels of autistic-like traits on the Autism Spectrum Quotient. We found that threatening faces inserted as the second target in a rapid serial visual presentation were identified more accurately among individuals with low- compared to high-levels of autistic-like traits. This is the first study to show that attentional blink abnormalities seen in autism extend to the neurotypical population with autistic-like traits, adding to the growing body of research suggesting that autistic-related patterns of behaviors extend into a subset of the neurotypical population. Autism Res 2017, 10: 311-320. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 27385676 TI - Preface to the Special Section on the Impact of Thomas Waters on the Field of Ergonomics. PMID- 27385678 TI - Introducing JBJS Open Access. PMID- 27385677 TI - Great Expectations: How Role Expectations and Role Experiences Relate to Perceptions of Group Cohesion. AB - Many athletes experience a discrepancy between the roles they expect to fulfill and the roles they eventually occupy. Drawing from met expectations theory, we applied response surface methodology to examine how role expectations, in relation to role experiences, influence perceptions of group cohesion among Canadian Interuniversity Sport athletes (N = 153). On the basis of data from two time points, as athletes approached and exceeded their role contribution expectations, they reported higher perceptions of task cohesion. Furthermore, as athletes approached and exceeded their social involvement expectations, they reported higher perceptions of social cohesion. These response surface patterns pertaining to task and social cohesion-were driven by the positive influence of role experiences. On the basis of the interplay between athletes' role experiences and their perception of the group environment, efforts to improve team dynamics may benefit from focusing on improving the quality of role experiences, in conjunction with developing realistic role expectations. PMID- 27385679 TI - Bone Morphogenetic Protein Use and Cancer Risk Among Patients Undergoing Lumbar Arthrodesis: A Case-Cohort Study Using the SEER-Medicare Database. AB - BACKGROUND: Recombinant bone morphogenetic proteins (BMPs) are growth factors utilized in lumbar arthrodeses. Limited data from randomized trials suggest that BMP may increase cancer risk. We sought to evaluate cancer risk and mortality following the use of BMP in lumbar arthrodesis. METHODS: Within the linked Surveillance, Epidemiology, and End Results (SEER) Program-Medicare cohort, we conducted a case-cohort study of 7,278 individuals who were >=65 years of age and had undergone a lumbar arthrodesis from 2004 to 2011. Of these patients, 3,627 were individuals in a 5% random subcohort of Medicare enrollees in SEER areas including 191 who developed cancer, and there were 3,651 individuals outside the subcohort who developed cancer. Weighted Cox proportional-hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for cancer on the basis of exposure to BMP. RESULTS: In the SEER-Medicare subcohort, 30.7% of individuals who underwent a lumbar arthrodesis received BMP. BMP was not associated with overall cancer risk in univariate analyses (HR, 0.92 [95% CI, 0.82 to 1.02]) or after adjustment for demographic characteristics, comorbidities, hospital size, history of cancer, and calendar year (adjusted HR, 0.94 [95% CI, 0.84 to 1.05]). Individual cancer types were also not significantly elevated (p > 0.05 for all) in BMP users compared with nonusers. In addition, BMP use was not associated with a new cancer in people who had cancer prior to undergoing lumbar arthrodesis (adjusted HR, 1.04 [95% CI, 0.71 to 1.52]) or with mortality after a cancer diagnosis (adjusted HR, 1.05 [95% CI, 0.93 to 1.19]). CONCLUSIONS: In a large population of elderly U.S. adults undergoing lumbar arthrodesis, BMP use was not associated with cancer risk or mortality. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 27385680 TI - Avoidance of "Final" Surgical Fusion After Growing-Rod Treatment for Early-Onset Scoliosis. AB - BACKGROUND: Definitive "final" surgical fusion is the common end point for growing-rod treatment of early-onset scoliosis. However, final surgical fusion may be unnecessary for patients who have reached skeletal maturity with good alignment. This study characterizes patients who completed growing-rod treatment but did not undergo final surgical fusion. METHODS: Using a multicenter early onset-scoliosis database, we identified 167 patients who received growing-rod treatment from 1995 through 2010, reached skeletal maturity, and had a minimum 2 year follow-up after their last surgery. Thirty patients did not undergo final surgical fusion (observation group) and were compared clinically and radiographically with 137 patients who did undergo final fusion (final surgical fusion group). RESULTS: No significant differences were found between the groups with regard to the age at which treatment was initiated (p = 0.127), distribution of diagnoses (p = 0.84), or number of lengthening procedures (p = 0.692). In the observation group, 26 patients retained the growing rods and 4 patients had them removed at the last surgery because of infection. The mean primary curve correction at the end of treatment was 48% (from an initial mean magnitude of 79 degrees to a mean final curve of 41 degrees ) in the observation group compared with 38% (from 74 degrees to 46 degrees ) in the final surgical fusion group. There was no significant difference in final curve magnitude (41 degrees in the observation group and 46 degrees in the final surgical fusion group; p = 0.182). The mean increase in trunk height was 30.5% in the observation group and 35% in the final surgical fusion group. The final trunk height in the observation group was not significantly less than that in the final surgical fusion group (p = 0.142). CONCLUSIONS: Because of progressive ankylosis, avoiding final surgical fusion at skeletal maturity is a viable option for patients treated with growing rods for all diagnostic subgroups of early-onset scoliosis who have satisfactory final alignment and trunk height, a minimal gain in length at the last distraction, and no clinical or radiographic evidence of implant-related problems. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 27385681 TI - Surgical Technique Trends in Primary ACL Reconstruction from 2007 to 2014. AB - BACKGROUND: The surgical technique for anterior cruciate ligament (ACL) reconstruction has evolved as a result of improved understanding of ligament biomechanics, anatomy, device development, and failed reconstructions. Studies on surgical technique preferences have been limited to surgeon surveys, which are subject to selection and recall bias. The purpose of this study was to evaluate ACL reconstruction surgical technique and yearly revision rate trends in a community-based setting. METHODS: A population-based epidemiological study was conducted using data on primary ACL reconstruction procedures registered in an ACL reconstruction registry from 2007 to 2014. Changes in the incidence rates of different types of femoral tunnel drilling methods, different types of grafts and graft fixation, and revisions were studied. Adjusted incidence rate ratios (IRRs) are provided. RESULTS: Of the 21,686 ACL reconstructions studied, 72.4% were performed by sports medicine fellowship-trained surgeons. The incidence rate of femoral tunnel drilling via a tibial tunnel decreased at an adjusted rate of 26% per year (IRR = 0.74, 95% confidence interval [CI] = 0.71 to 0.78), from 56.4% to 17.6% during the study period. The incidence rate of medial portal drilling increased from 41.3% to 65.1% at an adjusted rate of 11% per year (IRR = 1.11, 95% CI = 1.09 to 1.13), and the incidence rate of drilling through a lateral approach increased from 2.3% to 17.3% at an adjusted rate of 53% per year (IRR = 1.53, 95% CI = 1.39 to 1.67). There was no change in the use of hamstring autograft, bone-patellar tendon-bone autograft, or tibial tendon allograft. Use of first-generation bioabsorbable femoral and tibial fixation decreased for all graft types. For soft-tissue grafts, usage of suspensory metal femoral fixation increased 12% to 13% per year (IRR = 1.12, 95% CI = 1.09 to 1.15 for tibial tendon grafts; IRR = 1.13, 95% CI = 1.10 to 1.15 for hamstring grafts). For bone patellar tendon-bone autografts, the use of femoral fixation with interference biocomposite screws increased 7% per year (IRR = 1.07, 95% CI = 1.04 to 1.10). On the tibial side, utilization of biocomposite screws increased for all graft types. No association was found between revision rate and the year of the primary operation. CONCLUSIONS: Surgeons changed their femoral tunnel drilling technique over the study period, whereas the incidence rates of specific graft utilization remained stable. There has been a shift away from first-generation bioabsorbable fixation and increasing use of biocomposite fixation across all graft types. Early cumulative revision rates remained stable. PMID- 27385682 TI - Clinical and Radiographic Results of an All-Polyethylene Pegged Bone-Ingrowth Glenoid Component. AB - BACKGROUND: Loosening of the glenoid component continues to be the main cause of medium and long-term failure of shoulder replacements. The purpose of this study was to evaluate the early clinical and radiographic results following use of an all-polyethylene pegged glenoid component designed for hybrid (biological and cement) fixation. METHODS: Eighty-three shoulders in 77 patients (mean age, 68.6 years) underwent total shoulder arthroplasty with a pegged hybrid-fixation component (bone-ingrowth glenoid and cemented peg). Outcomes were determined with the American Shoulder and Elbow Surgeons (ASES) score and the Oxford shoulder score. A detailed analysis of radiographs and fine-slice computed tomography (CT) images was performed to determine the extent of bone ingrowth between the flanges and the extent of radiolucent lines at the prosthesis-bone interface. RESULTS: The mean duration of follow-up was 46.7 months (range, 24 to 99 months). At the time of final follow-up, the median ASES score was 97 points (range, 43 to 100 points) and the median Oxford score was 48 points (range, 24 to 48 points). The median active forward elevation was 130 degrees (range, 65 degrees to 170 degrees ), median external rotation was 45 degrees (range, 5 degrees to 80 degrees ), and median internal rotation was to T11 (range, buttock to T4). Seventy-eight shoulders demonstrated a perfect Lazarus score for radiolucency (0, indicating no radiolucency). Sixty-eight shoulders demonstrated complete osseointegration, with bone ingrowth between all of the flanges seen on coronal CT; 5 demonstrated partial osseointegration; and 10 demonstrated osteolysis around the central peg. Most radiolucent lines were in the inferior Yian zones. There were no correlations between the Yian CT scores and either the ASES or Oxford score (rho = 0.13 and 0.07, respectively). CONCLUSIONS: Total shoulder arthroplasty with an all-polyethylene pegged glenoid component, utilizing hybrid fixation, demonstrated excellent clinical and radiographic results at the time of early follow-up. Radiolucent lines were seen most commonly around the inferior pegs of the prosthesis, and this may represent an incipient mode of failure. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 27385683 TI - Outcomes of Low-Energy Basicervical Proximal Femoral Fractures Treated with Cephalomedullary Fixation. AB - BACKGROUND: Basicervical peritrochanteric fractures are relatively rare, with 1.8% to 7.6% of hip fractures being identified as true basicervical fractures. The compression hip screw traditionally has been considered the "gold standard" for operative fixation of peritrochanteric fractures, with generally good results. The purpose of this study was to report the outcomes of basicervical peritrochanteric fractures of the proximal part of the femur treated with cephalomedullary nailing (CMN). METHODS: We reviewed medical records and radiographs of all patients at our institution with a peritrochanteric fracture treated with CMN from 2010 to 2012 (246 patients). Fourteen patients with a 2 part basicervical fracture were identified. Two of them died less than 6 weeks after injury and another patient did not return for follow-up. Eleven patients were included in the reported series. RESULTS: Five of the 11 patients had fracture-healing without complications. Their average tip-apex distance was 14.9 mm. The fixation failed in the remaining six patients, all of whom had a tip-apex distance of <25 mm, with an average of 17.4 mm. Four of the failures followed an anatomic reduction, and the other 2 followed a nearly anatomic reduction. CONCLUSIONS: CMN may be inadequate for fixation of 2-part basicervical fractures. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 27385684 TI - Anatomic Investigation of Commonly Used Landmarks for Evaluating Rotation During Forearm Fracture Reduction. AB - BACKGROUND: Evaluating rotation during open reduction and internal fixation of a forearm fracture is of paramount importance. In challenging cases, surgeons may utilize radiographic relationships between proximal and distal radial and ulnar landmarks to assess rotational position. However, to our knowledge, limited anatomic data are available to confirm these relationships. METHODS: Six hundred cadaveric radii and ulnae were obtained. Digital representations of the bicipital tuberosity, the radial styloid, the coronoid process, and the ulnar styloid were acquired, and the rotational profiles between respective landmarks were calculated. In order to validate the results and investigate the ability to differentiate rotated osseous positions, each bone was imaged in increments of 10 degrees of rotation and the profile of each landmark was measured. RESULTS: The radial styloid was at a mean of 158 degrees +/- 14 degrees of supination relative to the bicipital tuberosity. The ulnar styloid was at a mean of 185 degrees +/- 14 degrees of supination relative to the coronoid process. Imaging of the bones in increments of 10 degrees of rotation supported the relationships above. It was also found that a 1-mm difference in profile size corresponded to up to 60 degrees of rotation for the average ulna, compared with 10 degrees for the average radius. CONCLUSIONS: Our findings suggest that using the bicipital tuberosity and the radial styloid to assess intraoperative rotation of the radius on anteroposterior radiographs may be of limited value; the landmarks were not generally 180 degrees apart. Although the rotational positions of the coronoid process and the ulnar styloid were, on average, closer to 180 degrees , surgeons should be aware of the wide range of normal anatomy as well as the inability to judge rotation by as much as 60 degrees , even for an "ideal" ulna. CLINICAL RELEVANCE: This study, to our knowledge, represents the first anatomic investigation of the rotational profiles between the osseous landmarks used to assess forearm rotation after fracture. We recommend that surgeons first image the bicipital tuberosity at its largest profile, supinate the arm 20 degrees , and confirm that the radial styloid is at its largest profile. The ulna can then be assessed to support the lack of rotational deformity in the forearm. PMID- 27385685 TI - Talar Osteonecrosis Related to Adult Sickle Cell Disease: Natural Evolution from Early to Late Stages. AB - BACKGROUND: Little is known about the rate of, and factors affecting, progression of talar osteonecrosis related to sickle cell disease. Adult patients with sickle cell disease who presented with hip osteonecrosis were evaluated for talar osteonecrosis with radiographs and magnetic resonance imaging (MRI). Forty-five of them (75 tali) were diagnosed with talar osteonecrosis, and this group was evaluated for factors influencing the progression of the disease. METHODS: Forty five patients with sickle cell disease and osteonecrosis of the talus were identified with radiographs and MRI between 1985 and 1995. Seven of these patients were homozygous for hemoglobin S (S/S genotype), 26 had hemoglobin S/hemoglobin C, and 12 had hemoglobin S/beta-thalassemia. The talar osteonecrosis was graded with radiographs and MRI. The patients were followed with clinical examination and radiographs every 6 months until talar collapse and every year after the collapse. RESULTS: The osteonecrosis was unilateral in 15 patients and bilateral in 30 at the time of the initial examination. Forty-five ankles were asymptomatic and 30 were symptomatic at the initial evaluation. MRI performed at the time of the most recent follow-up, and compared with MRI performed at diagnosis, did not show partial or total regression of the osteonecrosis in any of the patients, even those with asymptomatic stage-I osteonecrosis. At the time of the most recent follow-up (mean, 20 years; range, 15 to 25 years), pain and collapse had developed in all except 12 ankles. The stage of the osteonecrosis at the initial visit, pain, the genotype of the sickle cell disease, and the extent and location of the lesion in the talus were risk factors for progression of the disease. CONCLUSIONS: In the majority of the patients with sickle cell disease, osteonecrosis of the talus should be expected to show relevant clinical and radiographic evidence of progression over a long period. LEVEL OF EVIDENCE: Prospective Level II. See Instructions for Authors for a complete description of levels of evidence. PMID- 27385686 TI - HIF-1-Dependent IL-6 Activation in Articular Chondrocytes Initiating Synovitis in Femoral Head Ischemic Osteonecrosis. AB - BACKGROUND: Ischemic osteonecrosis of the femoral head in children is associated with chronic hip synovitis and increased levels of the pro-inflammatory cytokine interleukin-6 (IL-6) in the synovial fluid due to unknown mechanisms. The purpose of this study was to investigate hypoxia-inducible factor-1 (HIF-1) activation as a molecular mechanism linking the induction of ischemic osteonecrosis to IL-6 production and the initiation of hip synovitis. METHODS: Ischemic osteonecrosis was surgically induced in the right femoral head of 6 piglets. A histologic score, synovial fluid volume, and IL-6 level were used to assess hip synovitis. IL-6 immunostaining of articular cartilage and synovial tissue was performed as well. To study the role of HIF-1 in IL-6 activation, in vitro experiments using an HIF-1alpha activator (deferoxamine) and inhibitor (HIF-1 small interfering-RNA [siRNA]) were carried out. Synovial cell responses to hypoxic chondrocyte conditioned media with and without an IL-6 receptor blocker (tocilizumab) were assessed on the basis of IL-1beta and tumor necrosis factor-alpha (TNF-alpha) gene expressions and with a synovial cell-proliferation assay. RESULTS: Induction of ischemic osteonecrosis produced hip synovitis and increased IL-6 levels in the synovial fluid. Immunostaining and protein analysis demonstrated articular chondrocytes as a source of increased IL-6 production. When articular chondrocytes were cultured under hypoxic conditions, significantly increased HIF 1alpha and IL-6 expressions were observed. Under hypoxic culture conditions, IL-6 gene expression was significantly increased by HIF-1alpha activation using deferoxamine and inhibited by HIF-1alpha inhibition using HIF-1 siRNA. Synovial cells exposed to hypoxic chondrocyte-conditioned medium showed significant increases in IL-1beta and TNF-alpha gene expressions and cell proliferation, which were inhibited by the IL-6 receptor blocker tocilizumab. CONCLUSIONS: Induction of ischemic osteonecrosis results in IL-6 production in the articular cartilage through an HIF-1-dependent pathway. IL-6 produced by hypoxic articular chondrocytes stimulates inflammatory cytokine responses in synovial cells, which were significantly decreased by tocilizumab. CLINICAL RELEVANCE: This study provides new insight into the inherent relationship between the induction of ischemia and the initiation of hip synovitis following ischemic osteonecrosis and suggests a potential therapeutic target in the treatment of the synovitis. PMID- 27385689 TI - Global Forum: An International Perspective on Outpatient Surgical Procedures for Adult Hip and Knee Reconstruction. AB - Outpatient surgical procedures for adult hip and knee reconstruction are gaining interest on a worldwide basis and have been progressively increasing over the last few years. Preoperative screening needs to concentrate on both the patient's comorbidities and home environment to provide a proper alignment of expectations of the surgeon, the patient, and the patient's family. Preoperative multidisciplinary patient information covering all aspects of the upcoming treatment course is a mandatory step, focusing on pain management and early mobilization. Perioperative pain management includes both multimodal and preventive analgesia. Preemptive medications, minimization of narcotics, and combination of general and regional anesthesia are the techniques required in joint arthroplasty performed as an outpatient surgical procedure. A multimodal blood loss management program should be used with preoperative identification of anemia and attention directed toward minimizing blood loss, considering the use of tranexamic acid during the surgical procedure. Postoperative care extends from the initial recovery from anesthesia to the physical therapist's evaluation of the patient's ambulatory status. After the patient has met the criteria for discharge and has been discharged on the same day of the surgical procedure, a nurse should call the patient later at home to check on wound status, pain control, and muscle weakness, which will be further addressed by physiotherapy and education. Implementing outpatient arthroplasty requires monitoring safety, patient satisfaction, and economic impact. PMID- 27385687 TI - Tissue Engineering in Orthopaedics. AB - ?It is important to carefully select the most appropriate combination of scaffold, signals, and cell types when designing tissue engineering approaches for an orthopaedic pathology.?Although clinical studies in which the tissue engineering paradigm has been applied in the treatment of orthopaedic diseases are limited in number, examining them can yield important lessons.?While there is a rapid rate of new discoveries in the basic sciences, substantial regulatory, economic, and clinical issues must be overcome with more consistency to translate a greater number of technologies from the laboratory to the operating room. PMID- 27385690 TI - Trends in Bone-Block Augmentation Among Recently Trained Orthopaedic Surgeons Treating Anterior Shoulder Instability. AB - BACKGROUND: Shoulder instability is a common entity requiring surgical stabilization. Although arthroscopic soft-tissue stabilization has been the most common surgical treatment, increased attention is now being paid to Latarjet coracoid transfers and bone-block augmentation, particularly with glenoid bone loss. The purpose of this work was to evaluate the current status of arthroscopic soft-tissue stabilization and bone-block augmentation stabilization techniques among newly trained orthopaedic surgeons in the United States. METHODS: The American Board of Orthopaedic Surgery (ABOS) database was utilized to identify shoulder instability cases submitted by ABOS Part-II Board Certification examination candidates. Cases were dichotomized into two groups: isolated soft tissue stabilizations and bone-block augmentation procedures, including coracoid transfer. The two groups were then analyzed to determine trends in annual incidence, complication rates, types of complications, concomitant procedures, surgeon fellowship training, and geographic region of practice. RESULTS: From 2004 to 2013, 6,854 surgeons submitted 7,587 shoulder instability surgical cases that met all inclusion criteria. Of these, 7,515 (99.1%) were isolated soft tissue stabilizations, and 72 (0.95%) were bone-block glenoid augmentations. Surgeons with sports medicine fellowship training performed 61.85% of isolated soft-tissue stabilization procedures and 58.33% of bone-block stabilization procedures. The percentage of stabilization cases that utilized bone-block augmentation increased tenfold from 0.14% to 1.4% (p = 0.029) during the study period. The overall annual incidence of isolated soft-tissue stabilizations (p = 0.037) and bone-block procedures (p = 0.016) increased from 2004 to 2013. Although the complication rate of the bone-block procedures remained steady (mean rate, 20.8%; p = 0.932), the isolated soft-tissue stabilization complication rate rose from 4.9% to 9.0% (mean rate, 5.4%; p = 0.003). CONCLUSIONS: A trend exists toward increased utilization of bone-block stabilization for the treatment of shoulder instability among recently trained orthopaedic surgeons. Complication rates remained relatively high (20.8%) for these procedures, but did not increase as was seen with the isolated soft-tissue stabilizations. Residency and fellowship programs should continue to focus on methods to optimize training for these procedures. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 27385691 TI - Bone Morphogenetic Proteins in Lumbar Arthrodesis: What Is All the Debate About? Commentary on an article by Daniel C. Beachler, PhD, MHS, et al.: "Bone Morphogenetic Protein Use and Cancer Risk Among Patients Undergoing Lumbar Arthrodesis: A Case-Cohort Study Using the SEER-Medicare Database". PMID- 27385692 TI - Words, cultural competence matter in LGBT patient care. PMID- 27385693 TI - New Drugs and Dosage Forms. PMID- 27385694 TI - Opioid control law in Vermont addresses provider status for pharmacists. PMID- 27385695 TI - ASHP 2016 Official Board and Section Elections. PMID- 27385696 TI - Advancing responsible use of medicines globally: The revised Basel Statements. PMID- 27385697 TI - Carbapenem-resistant Escherichia coli resistant to ceftazidime-avibactam: The need for a commercially available testing product. PMID- 27385698 TI - Mild hyperamylasemia and early-phase drug-induced pancreatitis. PMID- 27385699 TI - Falsely elevated acetaminophen levels in a patient with extreme hyperbilirubinemia. PMID- 27385700 TI - Using computerized prescriber order entry to limit overrides from automated dispensing cabinets. PMID- 27385701 TI - Olaparib for the treatment of BRCA-mutated advanced ovarian cancer. AB - PURPOSE: The pharmacology, clinical efficacy, safety, dosage and administration, and role in therapy of olaparib, a first-in-class treatment for advanced treatment-refractory ovarian cancer, are reviewed. SUMMARY: Olaparib (Lynparza, AstraZeneca) is an oral inhibitor of poly(ADP-ribose) polymerase (PARP) proteins that play a key role in DNA repair and genomic stability. Olaparib is indicated for use in treating certain patients with advanced, recurrent ovarian cancer who have mutations of the breast cancer 1 gene (BRCA1) or breast cancer 2 gene (BRCA2). In patients with BRCA-mutated cancers, olaparib blocks vital PARP mediated tumor cell DNA repair mechanisms, leading to "synthetic lethality" and selective tumor cell death. In Phase II clinical trials including patients with platinum-sensitive, platinum-resistant, and platinum-refractory ovarian cancers, olaparib significantly improved progression-free survival, with similar rates of response reported in patients with BRCA1- and BRCA2-mutated disease. Olaparib is generally well tolerated; the most commonly reported adverse events in clinical trials were mild nausea, fatigue, vomiting, and diarrhea. Severe anemia and severe fatigue can occur in association with olaparib treatment. Concurrent administration of olaparib and strong or moderate inducers or inhibitors of cytochrome P-450 isozyme 3A should be avoided, as use of those agents may alter plasma concentrations of olaparib. CONCLUSION: Olaparib is a novel PARP inhibitor that is efficacious and well tolerated in patients with BRCA-mutated advanced ovarian cancers who have received three or more lines of prior treatment. PMID- 27385702 TI - Prasugrel hypersensitivity with respiratory distress and rash. AB - PURPOSE: An adverse drug reaction associated with the use of prasugrel for dual antiplatelet therapy after percutaneous coronary intervention (PCI) with stent placement is reported. SUMMARY: About one week after starting prasugrel use following angioplasty and a stent revision procedure, a 61-year-old woman arrived in the emergency department with wheezing, shortness of breath, a feeling of throat closure, and a widespread erythematous, maculopapular, pruritic rash. She reported that the respiratory symptoms had started to develop the previous day, with the onset of rash occurring about 24 hours after initiation of prasugrel therapy. The patient's symptoms subsided after administration of 0.3 mg epinephrine subcutaneously, diphenhydramine 50 mg i.v., and methylprednisolone 125 mg i.v. Prasugrel was discontinued, and the patient was switched to another P2Y12 inhibitor (ticagrelor) for continued dual antiplatelet therapy. Analysis of the case using the adverse drug reaction probability scale of Naranjo et al. indicated that prasugrel was the probable cause of the hypersensitivity reaction. Hypersensitivity manifesting as a rash has been previously reported in patients receiving prasugrel, a thienopyridine P2Y12 inhibitor. Desensitization may be an option for thienopyridine-allergic patients undergoing PCI with stenting; alternatively, the nonthienopyridine P2Y12 inhibitor ticagrelor may be used in a dual antiplatelet therapy regimen. CONCLUSION: A patient who had undergone PCI with stenting developed shortness of breath and rash associated with prasugrel therapy. Symptoms abated after supportive therapy and discontinuation of prasugrel, the probable offending agent. Treatment was safely switched to ticagrelor. PMID- 27385703 TI - Stability of dronabinol capsules when stored frozen, refrigerated, or at room temperature. AB - PURPOSE: Results of a study to determine the 90-day stability of dronabinol capsules stored under various temperature conditions are reported. METHODS: High performance liquid chromatography (HPLC) with ultraviolet (UV) detection was used to assess the stability of dronabinol capsules (synthetic delta-9 tetrahydrocannabinol [Delta9-THC] mixed with high-grade sesame oil and other inactive ingredients and encapsulated as soft gelatin capsules) that were frozen, refrigerated, or kept at room temperature for three months. The dronabinol capsules remained in the original foil-sealed blister packs until preparation for HPLC-UV assessment. The primary endpoint was the percentage of the initial Delta9 THC concentration remaining at multiple designated time points. The secondary aim was to perform forced-degradation studies under acidic conditions to demonstrate that the HPLC-UV method used was stability indicating. RESULTS: The appearance of the dronabinol capsules remained unaltered during frozen, cold, or room temperature storage. Regardless of storage condition, the percentage of the initial Delta9-THC content remaining was greater than 97% for all evaluated samples at all time points over the three-month study. These experimental data indicate that the product packaging and the sesame oil used to formulate dronabinol capsules efficiently protect Delta9-THC from oxidative degradation to cannabinol; this suggests that pharmacies can store dronabinol capsules in nonrefrigerated automated dispensing systems, with a capsule expiration date of 90 days after removal from the refrigerator. CONCLUSION: Dronabinol capsules may be stored at room temperature in their original packaging for up to three months without compromising capsule appearance and with minimal reduction in Delta9-THC concentration. PMID- 27385704 TI - Prediction of inventory sustainability during a drug shortage. AB - PURPOSE: A methodology for predicting how long the on-hand inventory of a given medication will last during a supply shortage is described; a practical example of application of the methodology is provided. METHODS: Single-site data on consumption of i.v. tobramycin over an eight-month evaluation period were collected using commercial software that tabulates barcode-assisted medication administration (BCMA) events; administered doses were standardized as 1200-mg "vial-equivalents" and summed over the review period. The total number of vial equivalents consumed was divided by the number of "non-zero weeks of consumption" (i.e., weeks during which any tobramycin use occurred) to obtain a mean +/- S.D. weekly consumption rate; this rate was multiplied by the total i.v. tobramycin on hand supply (in vial-equivalents) to determine the mean number of potentially sustainable weeks of therapy in the event a shortage were to restrict the future supply of the drug. RESULTS: Overall, 99.6 vial-equivalents of i.v. tobramycin were used during the evaluation period. The mean +/- S.D. number of vial equivalents used per non-zero week of consumption was 3.11 +/- 1.26. A manual count of pharmacy inventory revealed that 102.9 vial-equivalents were available at the time of analysis. The mean predicted duration of supply was 33 weeks (95% confidence interval, -126 to 192 weeks). CONCLUSION: Available BCMA data on tobramycin consumption over eight months were used to calculate the mean number of weeks the on-hand supply of the drug could be expected to last during a persistent drug shortage. PMID- 27385706 TI - Athlete Characteristics and Team Competitive Performance as Moderators for the Relationship Between Coach Transformational Leadership and Athlete Performance. AB - The goal of this study is to examine the effects of coaches' transformational leadership on player performance. To advance existing research, we examine (a) effects on individual and team performance and (b) consider joint moderating effects of players' win orientation and teams' competitive performance on the leadership- individual performance link. In a three-source sample from German handball teams, we collected data on 336 players and 30 coaches and teams. Results showed positive main effects of transformational leadership's facet of articulating a vision (AV) on team and individual performance and negative main effects of providing an appropriate model (PAM) on team performance. With regard to moderating effects, AV increased and PAM decreased individual performance when both moderators were low, and intellectual stimulation had a positive effect when both were high. This study expands insights into the potential and limitation of transformational leadership with a strong focus on the role of situational contingencies. PMID- 27385707 TI - Performance of a Cartridge-Based Assay for Detection of Clinically Significant Human Papillomavirus (HPV) Infection: Lessons from VALGENT (Validation of HPV Genotyping Tests). AB - The Validation of Human Papillomavirus (HPV) Genotyping Tests (VALGENT) studies offer an opportunity to clinically validate HPV assays for use in primary screening for cervical cancer and also provide a framework for the comparison of analytical and type-specific performance. Through VALGENT, we assessed the performance of the cartridge-based Xpert HPV assay (Xpert HPV), which detects 14 high-risk (HR) types and resolves HPV16 and HPV18/45. Samples from women attending the United Kingdom cervical screening program enriched with cytologically abnormal samples were collated. All had been previously tested by a clinically validated standard comparator test (SCT), the GP5+/6+ enzyme immunoassay (EIA). The clinical sensitivity and specificity of the Xpert HPV for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and CIN3+ relative to those of the SCT were assessed as were the inter- and intralaboratory reproducibilities according to international criteria for test validation. Type concordance for HPV16 and HPV18/45 between the Xpert HPV and the SCT was also analyzed. The Xpert HPV detected 94% of CIN2+ and 98% of CIN3+ lesions among all screened women and 90% of CIN2+ and 96% of CIN3+ lesions in women 30 years and older. The specificity for CIN1 or less (<=CIN1) was 83% (95% confidence interval [CI], 80 to 85%) in all women and 88% (95% CI, 86 to 91%) in women 30 years and older. Inter- and intralaboratory agreements for the Xpert HPV were 98% and 97%, respectively. The kappa agreements for HPV16 and HPV18/45 between the clinically validated reference test (GP5+/6+ LMNX) and the Xpert HPV were 0.92 and 0.91, respectively. The clinical performance and reproducibility of the Xpert HPV are comparable to those of well-established HPV assays and fulfill the criteria for use in primary cervical cancer screening. PMID- 27385708 TI - Antimicrobial Stewardship in the Microbiology Laboratory: Impact of Selective Susceptibility Reporting on Ciprofloxacin Utilization and Susceptibility of Gram Negative Isolates to Ciprofloxacin in a Hospital Setting. AB - The objective of this study was to determine the impact of selective susceptibility reporting on ciprofloxacin utilization and Gram-negative susceptibility to ciprofloxacin in a hospital setting. Historically at our institution, the microbiology laboratory practice was to report ciprofloxacin susceptibility for all Enterobacteriaceae regardless of susceptibility to other agents. A selective reporting policy was implemented which involved the suppression of ciprofloxacin susceptibility to Enterobacteriaceae when there was lack of resistance to the antibiotics on the Gram-negative panel. Ciprofloxacin utilization (measured in defined daily doses [DDD] per 1,000 patient days) was collected before and after the intervention and compared to moxifloxacin, trimethoprim-sulfamethoxazole, nitrofurantoin, and amoxicillin-clavulanate. Monthly susceptibility of Pseudomonas aeruginosa and Escherichia coli to ciprofloxacin was tabulated. An interrupted time series analysis using segmented regression was performed. The mean monthly ciprofloxacin utilization decreased from 87 (95% CI, 83.7 to 91.2) to 39 (95% CI, 35.0 to 44.0) DDD per 1,000 patient days before and after the implementation of selective reporting, respectively. There was an immediate and sustained reduction in ciprofloxacin usage at 1, 3, 6, 12, and 24 months postintervention (P < 0.001). A compensatory increase in amoxicillin-clavulanate use was noted starting at 6 months postintervention and persisted for the study period (P < 0.027). Susceptibility of E. coli, but not that of P. aeruginosa, to ciprofloxacin was higher than predicted starting 12 months after the intervention (P < 0.05). In conclusion, selective reporting of ciprofloxacin susceptibly may be a useful intervention to reduce targeted antimicrobial utilization and improve Gram-negative susceptibility to ciprofloxacin. This approach should be considered as part of a broader multimodal antimicrobial stewardship program. PMID- 27385710 TI - Gods from the machine of medicine. PMID- 27385709 TI - Comparison of Next-Generation Sequencing Technologies for Comprehensive Assessment of Full-Length Hepatitis C Viral Genomes. AB - Affordable next-generation sequencing (NGS) technologies for hepatitis C virus (HCV) may potentially identify both viral genotype and resistance genetic motifs in the era of directly acting antiviral (DAA) therapies. This study compared the ability of high-throughput NGS methods to generate full-length, deep, HCV sequence data sets and evaluated their utility for diagnostics and clinical assessment. NGS methods using (i) unselected HCV RNA (metagenomics), (ii) preenrichment of HCV RNA by probe capture, and (iii) HCV preamplification by PCR implemented in four United Kingdom centers were compared. Metrics of sequence coverage and depth, quasispecies diversity, and detection of DAA resistance associated variants (RAVs), mixed HCV genotypes, and other coinfections were compared using a panel of samples with different viral loads, genotypes, and mixed HCV genotypes/subtypes [geno(sub)types]. Each NGS method generated near complete genome sequences from more than 90% of samples. Enrichment methods and PCR preamplification generated greater sequence depth and were more effective for samples with low viral loads. All NGS methodologies accurately identified mixed HCV genotype infections. Consensus sequences generated by different NGS methods were generally concordant, and majority RAVs were consistently detected. However, methods differed in their ability to detect minor populations of RAVs. Metagenomic methods identified human pegivirus coinfections. NGS provided a rapid, inexpensive method for generating whole HCV genomes to define infecting genotypes, RAVs, comprehensive viral strain analysis, and quasispecies diversity. Enrichment methods are particularly suited for high-throughput analysis while providing the genotype and information on potential DAA resistance. PMID- 27385711 TI - Turning Virchow upside down: medicine is politics on a smaller scale. PMID- 27385712 TI - Mindfulness may have risks as well as benefits. PMID- 27385713 TI - The importance of the loss of junior doctor's hours monitoring under the new contract. PMID- 27385714 TI - Medical intelligence, security and global health: the foundations of a new health agenda. AB - Medical intelligence, security and global health are distinct fields that often overlap, especially as the drive towards a global health security agenda gathers pace. Here, we outline some of the ways in which this has happened in the recent past during the recent Ebola epidemic in West Africa and in the killing of Osama Bin laden by US intelligence services. We evaluate medical intelligence and the role it can play in global health security; we also attempt to define a framework that illustrates how medical intelligence can be incorporated into foreign policy action in order delineate the boundaries and scope of this growing field. PMID- 27385715 TI - J Guy Scadding and the move from alternation to randomisation. PMID- 27385720 TI - Furthering the debate on the role of interstitial cells of Cajal in enteric inhibitory neuromuscular neurotransmission. AB - The gut, a muscular organ, performs a critical role in transporting ingested contents, yet it is also controlled to periodically stop transport to maximize digestion and toxin detection. The complex intraluminal composition and rheology challenge the mechanistic requirements of inhibitory neuromuscular neurotransmission. The interstitial cells of Cajal (ICCs)-generated slow wave may tune the promiscuous luminal chemical environment, which prepares the smooth muscle membrane potential for a depolarizing or hyperpolarizing response as needed. Slow waves are abolished during stimulation-induced inhibitory junction potentials (IJPs) due to purinergic-nitrergic tandem neurotransmission. Recent data demonstrating intact IJPs in a genomic knockout of ICCs provide rigorous evidence of the noncontribution of ICCs during evoked neurotransmission. This perspective article discusses the priority areas of investigations in enteric musculomotor transmission, for understanding its near-perfect design for chemical space sensing, as well as diseases in which the luminal transport braking process becomes dysfunctional, leading to delayed gastric emptying or intestinal transit. PMID- 27385719 TI - Dose-Response and Time Course Effects of Acute Resistance Exercise on Executive Function. AB - The purpose of this study was to examine possible dose-response and time course effects of an acute bout of resistance exercise on the core executive functions of inhibition, working memory, and cognitive flexibility. Twenty-eight participants (14 female; Mage = 20.5 +/- 2.1 years) completed a control condition and resistance exercise bouts performed at 40%, 70%, and 100% of their individual 10-repetition maximum. An executive function test battery was administered at 15 min and 180 min postexercise to assess immediate and delayed effects of exercise on executive functioning. At 15 min postexercise, high-intensity exercise resulted in less interference and improved reaction time (RT) for the Stroop task, while at 180 min low- and moderate-intensity exercise resulted in improved performance on plus-minus and Simon tasks, respectively. These findings suggest a limited and task-specific influence of acute resistance exercise on executive function in healthy young adults. PMID- 27385721 TI - 4-Hydroxy-2-nonenal: a critical target in oxidative stress? AB - In this perspective, we summarize and discuss critical advancements in the study of 4-hydroxy-2-nonenal (4-HNE) as it relates to diseases and clinical complications either caused or exacerbated by oxidative stress. Since its identification in 1980, 4-HNE has been extensively studied with an emphasis on its formation, its role in pathology, and its targets. As a reactive aldehyde, and a product of lipid peroxidation, studies corroborate its ability to disrupt signal transduction and protein activity, as well as induce inflammation and trigger cellular apoptosis in conditions of oxidative stress. Notably, we discuss the role of natural enzymes involved in the regulation of 4-HNE, and how they can be applied to its detoxification in various physiological conditions. PMID- 27385722 TI - EXPRESS: F-actin links Epac-PKC signaling to purinergic P2X3 receptors sensitization in dorsal root ganglia following inflammation. AB - Sensitization of purinergic P2X3 receptors (P2X3Rs) contributes to the production of exaggerated nociceptive responses following inflammatory injury. We showed previously that prostaglandin E2 (PGE2) potentiates P2X3R-mediated ATP currents in dorsal root ganglion neurons isolated from both control and complete Freund's adjuvant-induced inflamed rats. PGE2 potentiation of ATP currents depends only on PKA signaling in control neurons, but it depends on both PKA and PKC signaling in inflamed neurons. We further found that inflammation evokes an increase in exchange proteins directly activated by cAMP (Epacs) in dorsal root ganglions. This increase promotes the activation of PKC to produce a much enhanced PGE2 effect on ATP currents and to elicit Epac-dependent flinch nocifensive behavioral responses in complete Freund's adjuvant rats. The link between Epac-PKC signaling and P2X3R sensitization remains unexplored. Here, we show that the activation of Epacs promotes the expression of phosphorylated PKC and leads to an increase in the cytoskeleton, F-actin, expression at the cell perimeter. Depolymerization of F-actin blocks PGE2-enhanced ATP currents and inhibits P2X3R-mediated nocifensive responses after inflammation. Thus, F-actin is dynamically involved in the Epac PKC-dependent P2X3R sensitization. Furthermore, Epacs induce a PKC-dependent increase in the membrane expression of P2X3Rs. This increase is abolished by F actin depolymerization, suggesting that F-actin mediates Epac-PKC signaling of P2X3R membrane expression. Thus, after inflammation, an Epac-PKC dependent increase in F-actin in dorsal root ganglion neurons enhances the membrane expression of P2X3Rs to bring about sensitization of P2X3Rs and abnormal pain behaviors. PMID- 27385723 TI - EXPRESS: Voltage-dependent sodium (NaV) channels in group IV sensory afferents. AB - Patients with intermittent claudication suffer from both muscle pain and an exacerbated exercise pressor reflex. Excitability of the group III and group IV afferent fibers mediating these functions is controlled in part by voltage dependent sodium (NaV) channels. We previously found tetrodotoxin-resistant NaV1.8 channels to be the primary type in muscle afferent somata. However, action potentials in group III and IV afferent axons are blocked by TTX, supporting a minimal role of NaV1.8 channels. To address these apparent differences in NaV channel expression between axon and soma, we used immunohistochemistry to identify the NaV channels expressed in group IV axons within the gastrocnemius muscle and the dorsal root ganglia sections. Positive labeling by an antibody against the neurofilament protein peripherin was used to identify group IV neurons and axons. We show that >67% of group IV fibers express NaV1.8, NaV1.6, or NaV1.7. Interestingly, expression of NaV1.8 channels in group IV somata was significantly higher than in the fibers, whereas there were no significant differences for either NaV1.6 or NaV1.7. When combined with previous work, our results suggest that NaV1.8 channels are expressed in most group IV axons, but that, under normal conditions, NaV1.6 and/or NaV1.7 play a more important role in action potential generation to signal muscle pain and the exercise pressor reflex. PMID- 27385724 TI - EXPRESS: Histone hyperacetylation modulates spinal type II metabotropic glutamate receptor alleviating stress-induced visceral hypersensitivity in female rats. AB - Stress is often a trigger to exacerbate chronic pain including visceral hypersensitivity associated with irritable bowel syndrome, a female predominant functional bowel disorder. Epigenetic mechanisms that mediate stress responses are a potential target to interfere with visceral pain. The purpose of this study was to examine the effect of a histone deacetylase inhibitor, suberoylanilide hydroxamic acid, on visceral hypersensitivity induced by a subchronic stressor in female rats and to investigate the involvement of spinal glutamate receptors. Three daily sessions of forced swim induced visceral hypersensitivity. Intrathecal suberoylanilide hydroxamic acid prevented or reversed the stress induced visceral hypersensitivity, increased spinal histone 3 acetylation and increased mGluR2 and mGluR3 expression. Chromatin immunoprecipitation (ChIP) analysis revealed enrichment of H3K9Ac and H3K18Ac at several promoter Grm2 and Grm3 regions. The mGluR2/3 antagonist LY341495 reversed the inhibitory effect of suberoylanilide hydroxamic acid on the stress-induced visceral hypersensitivity. In surprising contrast, stress and/or suberoylanilide hydroxamic acid had no effect on spinal NMDA receptor expression or function. These data reveal histone modification modulates mGluR2/3 expression in the spinal cord to attenuate stressinduced visceral hypersensitivity. HDAC inhibitors may provide a potential approach to relieve visceral hypersensitivity associated with irritable bowel syndrome. PMID- 27385725 TI - P66Shc, a key regulator of metabolism and mitochondrial ROS production, is dysregulated by mouse embryo culture. AB - STUDY QUESTION: Do high oxygen tension and high glucose concentrations dysregulate p66Shc (Src homologous-collagen homologue adaptor protein) expression during mouse preimplantation embryo culture? SUMMARY ANSWER: Compared with mouse blastocysts in vivo, P66Shc mRNA and protein levels in blastocysts maintained in vitro increased under high oxygen tension (21%), but not high glucose concentration. WHAT IS KNOWN ALREADY: Growth in culture adversely impacts preimplantation embryo development and alters the expression levels of the oxidative stress adaptor protein p66Shc, but it is not known if p66Shc expression is linked to metabolic changes observed in cultured embryos. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: We used a standard wild-type CD1 mouse model of preimplantation embryo development and embryo culture with different atmospheric oxygen tension and glucose media concentrations. Changes to p66Shc expression in mouse blastocysts were measured using quantitative RT-PCR, immunoblotting and immunofluorescence followed by confocal microscopy. Changes to oxidative phosphorylation metabolism were measured by total ATP content and superoxide production. Statistical analyses were performed on a minimum of three experimental replicates using Students' t-test or one-way ANOVA. MAIN RESULTS AND THE ROLE OF CHANCE: P66Shc is basally expressed during in vivo mouse preimplantation development. Within in vivo blastocysts, p66Shc is primarily localized to the cell periphery of the trophectoderm. Blastocysts cultured under atmospheric oxygen levels have significantly increased p66Shc mRNA transcript and protein abundances compared to in vivo controls (P < 0.05). However, the ratio of phosphorylated serine 36 (S36) p66Shc to total p66Shc decreased in culture regardless of O2 atmosphere used, supporting a shift in the mitochondrial fraction of p66Shc. Total p66Shc localized to the cell periphery of the blastocyst trophectoderm and phosphorylated S36 p66Shc displayed nuclear and cytoplasmic immunoreactivity, suggesting distinct compartmentalization of phosphorylated S36 p66Shc and the remaining p66Shc fraction. Glucose concentration in the culture medium did not significantly change p66Shc mRNA or protein abundance or its localization. Blastocysts cultured under low or high oxygen conditions exhibited significantly decreased cellular ATP and increased superoxide production compared to in vivo derived embryos (P < 0.05). LIMITATIONS/REASONS FOR CAUTION: This study associates embryonic p66Shc expression levels with metabolic abnormalities but does not directly implicate p66Shc in metabolic changes. Additionally, we used one formulation of embryo culture medium that differs from that used in other mouse model studies and from clinical media used to support human blastocyst development. Our findings may, therefore, be limited to this media, or may be a species-specific phenomenon. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to show distinct immunolocalization of p66Shc to the trophectoderm of mouse blastocysts and that its levels are abnormally increased in embryos exposed to culture conditions. Changes in p66Shc expression and/or localization could possibly serve as a molecular marker of embryo viability for clinical applications. The outcomes provide insight into the potential metabolic role of p66Shc. Metabolic anomalies are induced even under the current optimal culture conditions, which could negatively impact trophectoderm and placental development. LARGE SCALE DATA: Not applicable. STUDY FUNDING AND COMPETING INTERESTS: Canadian Institutes of Health Research (CIHR) operating funds, Ontario Graduate Scholarship (OGS). There are no competing interests. PMID- 27385726 TI - Microfluidic devices for the study of sperm migration. AB - Microfluidics technology offers us an opportunity to model the biophysical and biochemical environments encountered by sperm moving through the female reproductive tract and, at the same time, to study sperm swimming dynamics at a quantitative level. In humans, coitus results in the deposition of sperm in the vagina at the entrance to the cervix. Consequently, sperm must swim or be drawn through the cervix, uterus, uterotubal junction and oviductal isthmus to reach the oocyte in the oviductal ampulla. Only a very small percentage of inseminated sperm reach the ampulla in the periovulatory period, indicating that strong selection pressures act on sperm during migration. A better understanding of how sperm interact with the female tract would inspire improvements in diagnosis of fertility problems and development of novel-assisted reproductive technologies that minimize damage to sperm and mimic natural selection pressures on sperm. PMID- 27385727 TI - BMP signalling in human fetal ovary somatic cells is modulated in a gene-specific fashion by GREM1 and GREM2. AB - STUDY QUESTION: Do changes in the expression of bone morphogenetic proteins (BMPs) 2 and 4, and their antagonists Gremlin1 (GREM1) and Gremlin2 (GREM2) during human fetal ovarian development impact on BMP pathway activity and lead to changes in gene expression that may influence the fate and/or function of ovarian somatic cells? STUDY FINDING: BMPs 2 and 4 differentially regulate gene expression in cultured human fetal ovarian somatic cells. Expression of some, but not all BMP target genes is antagonised by GREM1 and GREM2, indicating the existence of a mechanism to fine-tune BMP signal intensity in the ovary. Leucine rich repeat-containing G-protein coupled receptor 5 (LGR5), a marker of immature ovarian somatic cells, is identified as a novel transcriptional target of BMP4. WHAT IS KNOWN ALREADY: Extensive re-organisation of the germ and somatic cell populations in the feto-neonatal ovary culminates in the formation of primordial follicles, which provide the basis for a female's future fertility. BMP growth factors play important roles at many stages of ovarian development and function. GREM1, an extracellular antagonist of BMP signalling, regulates the timing of primordial follicle formation in the mouse ovary, and mRNA levels of BMP4 decrease while those of BMP2 increase prior to follicle formation in the human fetal ovary. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Expression of genes encoding BMP pathway components, BMP antagonists and markers of ovarian somatic cells were determined by quantitative (q)RT-PCR in human fetal ovaries (from 8 to 21 weeks gestation) and fetal ovary-derived somatic cell cultures. Ovarian expression of GREM1 protein was confirmed by immunoblotting. Primary human fetal ovarian somatic cell cultures were derived from disaggregated ovaries by differential adhesion and cultured in the presence of recombinant human BMP2 or BMP4, with or without the addition of GREM1 or GREM2. MAIN RESULTS AND THE ROLE OF CHANCE: We demonstrate that the expression of BMP antagonists GREM1, GREM2 and CHRD increases in the lead-up to primordial follicle formation in the human fetal ovary, and that the BMP pathway is active in cultured ovarian somatic cells. This leads to differential changes in the expression of a number of genes, some of which are further modulated by GREM1 and/or GREM2. The positive transcriptional regulation of LGR5 (a marker of less differentiated somatic cells) by BMP4 in vitro suggests that increasing levels of GREM1 and reduced levels of BMP4 as the ovary develops in vivo may act to reduce LGR5 levels and allow pre-granulosa cell differentiation. LIMITATIONS, REASONS FOR CAUTION: While we have demonstrated that markers of different somatic cell types are expressed in the cultured ovarian somatic cells, their proportions may not represent the same cells in the intact ovary which also contains germ cells. WIDER IMPLICATIONS OF THE FINDINGS: This study extends previous work identifying germ cells as targets of ovarian BMP signalling, and suggests BMPs may regulate the development of both germ and somatic cells in the developing ovary around the time of follicle formation. LARGE SCALE DATA: Not applicable. STUDY FUNDING/COMPETING INTERESTS: This work was supported by The UK Medical Research Council (Grant No.: G1100357 to RAA), and Medical Research Scotland (Grant No. 345FRG to AJC). The authors have no competing interests to declare. PMID- 27385728 TI - ID2 mediates the transforming growth factor-beta1-induced Warburg-like effect seen in the peritoneum of women with endometriosis. AB - STUDY QUESTION: Is inhibitor of DNA-binding protein 2 (ID2) a mediator of the transforming growth factor (TGF)-beta1-induced Warburg-like effect seen in the peritoneum of women with endometriosis? SUMMARY ANSWER: The TGF-beta1-induced changes in the metabolic phenotype of peritoneal mesothelial cells from women with endometriosis are mediated through the ID2 pathway. WHAT IS KNOWN ALREADY: TGF-beta1 induces the metabolic conversion of glucose to lactate via aerobic glycolysis (the 'Warburg effect') in the peritoneum of women with endometriosis, through increased expression of the transcription factor hypoxia inducible factor alpha (HIF-1alpha). ID proteins are transcriptional targets of TGF-beta1. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Expression of ID2 was investigated in luteal phase peritoneal biopsies from women with regular menstrual cycles, with and without endometriosis (n = 8-10 each group) by quantitative RT-PCR (qRT-PCR) and immunohistochemistry. ID2 mRNA expression in primary human peritoneal mesothelial cells (HPMC) and immortalized mesothelial cells (MeT-5A) was assessed by qRT-PCR (n = 6). The effects of TGF-beta1 and ID2 siRNA on HIF-1alpha mRNA expression and lactate secretion was assessed using qRT-PCR and a colorimetric lactate assay. MAIN RESULTS AND THE ROLE OF CHANCE: ID2 is localized to peritoneal mesothelial and stromal cells of women with and without endometriosis. ID2 mRNA expression is lower in peritoneum adjacent to the endometriosis lesions compared to distal sites (P < 0.01). Exposure of HPMC and MeT-5A cells to physiological concentrations of TGF-beta1 decreases ID2 mRNA expression (P < 0.01, P < 0.001, respectively, versus control). ID2 knockdown increases HIF-1alpha mRNA expression (P < 0.01) and lactate secretion (P < 0.05 versus scrambled control) to the same degree as with exposure to TGF-beta1. LIMITATIONS, REASONS FOR CAUTION: Primary human cell cultures and a cell line were used in this study, and thus the results may not fully represent the situation in vivo. The results should also be replicated using a larger number of samples. WIDER IMPLICATIONS OF THE FINDINGS: Novel therapeutics that target the TGFbeta/ID pathway offer a potential role in the treatment of endometriosis. LARGE SCALE DATA: None. STUDY FUNDING AND COMPETING INTERESTS: This work was funded by a Wellbeing of Women research grant (R42533) awarded to A.W.H., J.K.B. and W.C.D.; and an MRC Centre Grant G1002033. V.J.Y. received grant support from Federation of Women Graduates (134225) and a PhD studentship from the College of Medicine and Veterinary Medicine at the University of Edinburgh. There are no competing interests to declare. PMID- 27385729 TI - Pharmacological Characterization of the Spectrum of Antiviral Activity and Genetic Barrier to Drug Resistance of M2-S31N Channel Blockers. AB - Adamantanes (amantadine and rimantadine) are one of the two classes of Food and Drug Administration-approved antiviral drugs used for the prevention and treatment of influenza A virus infections. They inhibit viral replication by blocking the wild-type (WT) M2 proton channel, thus preventing viral uncoating. However, their use was discontinued due to widespread drug resistance. Among a handful of drug-resistant mutants, M2-S31N is the predominant mutation and persists in more than 95% of currently circulating influenza A strains. We recently designed two classes of M2-S31N inhibitors, S31N-specific inhibitors and S31N/WT dual inhibitors, which are represented by N-[(5-cyclopropyl-1,2-oxazol-3 yl)methyl]adamantan-1-amine (WJ379) and N-[(5-bromothiophen-2-yl)methyl]adamantan 1-amine (BC035), respectively. However, their antiviral activities against currently circulating influenza A viruses and their genetic barrier to drug resistance are unknown. In this report, we evaluated the therapeutic potential of these two classes of M2-S31N inhibitors (WJ379 and BC035) by profiling their antiviral efficacy against multidrug-resistant influenza A viruses, in vitro drug resistance barrier, and synergistic effect with oseltamivir. We found that M2 S31N inhibitors were active against several influenza A viruses that are resistant to one or both classes of Food and Drug Administration-approved anti influenza drugs. In addition, M2-S31N inhibitors display a higher in vitro genetic barrier to drug resistance than amantadine. The antiviral effect of WJ379 was also synergistic with oseltamivir carboxylate. Overall, these results reaffirm that M2-S31N inhibitors are promising antiviral drug candidates that warrant further development. PMID- 27385730 TI - A Teacher-Focused Intervention to Decrease PE Students' Amotivation by Increasing Need Satisfaction and Decreasing Need Frustration. AB - Intervention-induced gains in need satisfaction decrease PE students' amotivation. The present study adopted a dual-process model to test whether an intervention could also decrease need frustration and hence provide a second supplemental source to further decrease students' PE amotivation. Using an experimental, longitudinal research design, 19 experienced PE teachers (9 experimental, 10 control) and their 1,017 students participated in an intervention program to help teachers become both more autonomy supportive and less controlling. Multilevel repeated measures analyses showed that students of teachers in the experimental group reported greater T2, T3, and T4 perceived autonomy support, need satisfaction, and engagement and lesser T2, T3, and T4 perceived teacher control, need frustration, and amotivation than did students of teachers in the control group. Multilevel structural equation modeling analyses confirmed the hypothesized dual-process model in which both intervention-induced increases in need satisfaction and intervention-induced decreases need frustration decreased students' end-of-semester amotivation. We discuss the theoretical and practical implications of this new finding on the dual antecedents of diminished amotivation. PMID- 27385731 TI - Oxidized fish oil in rat pregnancy causes high newborn mortality and increases maternal insulin resistance. AB - Fish oil is commonly taken by pregnant women, and supplements sold at retail are often oxidized. Using a rat model, we aimed to assess the effects of supplementation with oxidized fish oil during pregnancy in mothers and offspring, focusing on newborn viability and maternal insulin sensitivity. Female rats were allocated to a control or high-fat diet and then mated. These rats were subsequently randomized to receive a daily gavage treatment of 1 ml of unoxidized fish oil, a highly oxidized fish oil, or control (water) throughout pregnancy. At birth, the gavage treatment was stopped, but the same maternal diets were fed ad libitum throughout lactation. Supplementation with oxidized fish oil during pregnancy had a marked adverse effect on newborn survival at day 2, leading to much greater odds of mortality than in the control (odds ratio 8.26) and unoxidized fish oil (odds ratio 13.70) groups. In addition, maternal intake of oxidized fish oil during pregnancy led to increased insulin resistance at the time of weaning (3 wks after exposure) compared with control dams (HOMA-IR 2.64 vs. 1.42; P = 0.044). These data show that the consumption of oxidized fish oil is harmful in rat pregnancy, with deleterious effects in both mothers and offspring. PMID- 27385733 TI - Thermal conditions experienced during differentiation affect metabolic and contractile phenotypes of mouse myotubes. AB - Central pathways regulate metabolic responses to cold in endotherms to maintain relatively stable internal core body temperatures. However, peripheral muscles routinely experience temperatures lower than core body temperature, so that it would be advantageous for peripheral tissues to respond to temperature changes independently from core body temperature regulation. Early developmental conditions can influence offspring phenotypes, and here we tested whether developing muscle can compensate locally for the effects of cold exposure independently from central regulation. Muscle myotubes originate from undifferentiated myoblasts that are laid down during embryogenesis. We show that in a murine myoblast cell line (C2C12), cold exposure (32 degrees C) increased myoblast metabolic flux compared with 37 degrees C control conditions. Importantly, myotubes that differentiated at 32 degrees C compensated for the thermodynamic effects of low temperature by increasing metabolic rates, ATP production, and glycolytic flux. Myotube responses were also modulated by the temperatures experienced by "parent" myoblasts. Myotubes that differentiated under cold exposure increased activity of the AMP-stimulated protein kinase (AMPK), which may mediate metabolic changes in response cold exposure. Moreover, cold exposure shifted myosin heavy chains from slow to fast, presumably to overcome slower contractile speeds resulting from low temperatures. Adjusting thermal sensitivities locally in peripheral tissues complements central thermoregulation and permits animals to maintain function in cold environments. Muscle also plays a major metabolic role in adults, so that developmental responses to cold are likely to influence energy expenditure later in life. PMID- 27385732 TI - Ventral tegmental area orexin 1 receptors promote palatable food intake and oppose postingestive negative feedback. AB - Hypothalamic orexin neurons project to numerous brain areas, including the ventral tegmental area (VTA), which is involved in motivation and food-seeking behavior. Here we address how exogenously administered orexin-A and endogenous orexin 1 receptor (OX1R) activation in the VTA affects feeding behavior. We hypothesized that orexin-A and OX1R antagonist SB334867 delivered to the VTA, at doses that were subthreshold for effect when injected into the ventricle, would affect intake of palatable foods in multiple test situations. We first used a hedonic feeding model in which satiated rats selectively consume a high-fat diet (HFD). Intra-VTA orexin-A stimulated additional consumption of chow and increased HFD intake in this model. In ad libitum-fed rats given daily 30-min test sessions, intra-VTA orexin-A also increased intake of HFD and 0.1 M sucrose. Further analysis of licking patterns revealed that that VTA orexin-A increased meal size and licking burst size only toward the end of the meal. Consistent with this finding, a subthreshold dose of VTA orexin-A prevented intake suppression induced by gastrointestinal nutrient infusion. Surprisingly, intra-VTA orexin-A had no effect on operant responding for sucrose pellets on a progressive ratio schedule of reinforcement. A role for endogenous VTA OX1R stimulation is supported by our finding that bilateral VTA injection of the selective OX1R antagonist SB334867 suppressed 0.1 M sucrose intake. Together, our data suggest that OX1R activity in the VTA facilitates food intake, potentially by counteracting postingestive negative feedback that would normally suppress feeding later in a meal. PMID- 27385735 TI - The Effects of Acute Exercise on Memory and Brain-Derived Neurotrophic Factor (BDNF). AB - Acute exercise benefits cognition, and some evidence suggests that brain-derived neurotrophic factor (BDNF) plays a role in this effect. The purpose of this study was to explore the dose-response relationship between exercise intensity, memory, and BDNF. Young adults completed 3 exercise sessions at different intensities relative to ventilator threshold (Vt) (VO2max, Vt - 20%, Vt + 20%). For each session, participants exercised for approximately 30 min. Following exercise, they performed the Rey Auditory Verbal Learning Test (RAVLT) to assess short-term memory, learning, and long-term memory recall. Twenty-four hours later, they completed the RAVLT recognition trial, which provided another measure of long term memory. Blood was drawn before exercise, immediately postexercise, and after the 30-min recall test. Results indicated that long-term memory as assessed after the 24-hr delay differed as a function of exercise intensity with the largest benefits observed following maximal intensity exercise. BDNF data showed a significant increase in response to exercise; however, there were no differences relative to exercise intensity and there were no significant associations between BDNF and memory. Future research is warranted so that we can better understand how to use exercise to benefit cognitive performance. PMID- 27385734 TI - Bladder urine oxygen tension for assessing renal medullary oxygenation in rabbits: experimental and modeling studies. AB - Oxygen tension (Po2) of urine in the bladder could be used to monitor risk of acute kidney injury if it varies with medullary Po2 Therefore, we examined this relationship and characterized oxygen diffusion across walls of the ureter and bladder in anesthetized rabbits. A computational model was then developed to predict medullary Po2 from bladder urine Po2 Both intravenous infusion of [Phe(2),Ile(3),Orn(8)]-vasopressin and infusion of N(G)-nitro-l-arginine reduced urinary Po2 and medullary Po2 (8-17%), yet had opposite effects on renal blood flow and urine flow. Changes in bladder urine Po2 during these stimuli correlated strongly with changes in medullary Po2 (within-rabbit r(2) = 0.87-0.90). Differences in the Po2 of saline infused into the ureter close to the kidney could be detected in the bladder, although this was diminished at lesser ureteric flow. Diffusion of oxygen across the wall of the bladder was very slow, so it was not considered in the computational model. The model predicts Po2 in the pelvic ureter (presumed to reflect medullary Po2) from known values of bladder urine Po2, urine flow, and arterial Po2 Simulations suggest that, across a physiological range of urine flow in anesthetized rabbits (0.1-0.5 ml/min for a single kidney), a change in bladder urine Po2 explains 10-50% of the change in pelvic urine/medullary Po2 Thus, it is possible to infer changes in medullary Po2 from changes in urinary Po2, so urinary Po2 may have utility as a real-time biomarker of risk of acute kidney injury. PMID- 27385736 TI - SREBP inhibition ameliorates renal injury after unilateral ureteral obstruction. AB - Tubulointerstitial fibrosis is a major feature associated with declining kidney function in chronic kidney disease of diverse etiology. No effective means as yet exists to prevent the progression of fibrosis. We have shown that the transcription factor sterol-regulatory element-binding protein 1 (SREBP-1) is an important mediator of the profibrotic response to transforming growth factor-beta (TGF-beta) and angiotensin II, both key cytokines in the fibrotic process. Here, we examined the role of SREBP in renal interstitial fibrosis in the unilateral ureteral obstruction (UUO) model. The two isoforms of SREBP (-1 and -2) were activated by 3 days after UUO, with SREBP-1 showing a more sustained activation to 21 days. We then examined whether SREBP1/2 inhibition with the small-molecule inhibitor fatostatin could attenuate fibrosis after 14 days of UUO. SREBP activation was confirmed to be inhibited by fatostatin. Treatment decreased interstitial fibrosis, TGF-beta signaling, and upregulation of alpha-smooth muscle actin (SMA), a marker of fibroblast activation. Fatostatin also attenuated inflammatory cell infiltrate and apoptosis. Associated with this, fatostatin preserved proximal tubular mass. The significant increase in atubular glomeruli observed after UUO, known to correlate with irreversible renal functional decline, was also decreased by treatment. In cultured primary fibroblasts, TGF beta1 induced the activation of SREBP-1 and -2. Fatostatin blocked TGF-beta1 induced alpha-SMA and matrix protein upregulation. The inhibition of SREBP is thus a potential novel therapeutic target in the treatment of fibrosis in chronic kidney disease. PMID- 27385737 TI - 4-PBA improves lithium-induced nephrogenic diabetes insipidus by attenuating ER stress. AB - Endoplasmic reticulum (ER) stress has been implicated in some types of glomerular and tubular disorders. The objectives of this study were to elucidate the role of ER stress in lithium-induced nephrogenic diabetes insipidus (NDI) and to investigate whether attenuation of ER stress by 4-phenylbutyric acid (4-PBA) improves urinary concentrating defect in lithium-treated rats. Wistar rats received lithium (40 mmol/kg food), 4-PBA (320 mg/kg body wt by gavage every day), or no treatment (control) for 2 wk, and they were dehydrated for 24 h before euthanasia. Lithium treatment resulted in increased urine output and decreased urinary osmolality, which was significantly improved by 4-PBA. 4-PBA also prevented reduced protein expression of aquaporin-2 (AQP2), pS256-AQP2, and pS261-AQP2 in the inner medulla of kidneys from lithium-treated rats after 24-h dehydration. Lithium treatment resulted in increased expression of ER stress markers in the inner medulla, which was associated with dilated cisternae and expansion of ER in the inner medullary collecting duct (IMCD) principal cells. Confocal immunofluorescence studies showed colocalization of a molecular chaperone, binding IgG protein (BiP), with AQP2 in principal cells. Immunohistochemistry demonstrated increased intracellular expression of BiP and decreased AQP2 expression in IMCD principal cells of kidneys from lithium-treated rats. 4-PBA attenuated expression of ER stress markers and recovered ER morphology. In IMCD suspensions isolated from lithium-treated rats, 4-PBA incubation was also associated with increased AQP2 expression and ameliorated ER stress. In conclusion, in experimental lithium-induced NDI, 4-PBA improved the urinary concentrating defect and increased AQP2 expression, likely via attenuating ER stress in IMCD principal cells. PMID- 27385738 TI - A Reciprocal Effects Model of Children's Body Fat Self-Concept: Relations With Physical Self-Concept and Physical Activity. AB - This study investigated a reciprocal effects model (REM) of children's body fat self-concept and physical self-concept, and objectively measured school physical activity at different intensities. Grade four students (N = 376; M age = 9.07, SD = .61; 55% boys) from the midwest region of the United States completed measures of physical self-concept and body fat self-concept, and wore accelerometers for three consecutive school days at the beginning and end of one school year. Findings from structural equation modeling analyses did not support reciprocal effects. However, children's body fat self-concept predicted future physical self concept and moderate-to-vigorous physical activity (MVPA). Multigroup analyses explored the moderating role of weight status, sex, ethnicity, and sex*ethnicity within the REM. Findings supported invariance, suggesting that the observed relations were generalizable for these children across demographic groups. Links between body fat self-concept and future physical self-concept and MVPA highlight self-enhancing effects that can promote children's health and well-being. PMID- 27385739 TI - The Effects of Elaboration on the Strength of Doping-Related Attitudes: Resistance to Change and Behavioral Intentions. AB - This experiment analyzed whether attitudes toward the legalization of several doping behaviors would resist change and predict behavioral intentions when they were initially formed through thoughtful (i.e., high elaboration) versus nonthoughtful (i.e., low elaboration) processes. Participants were randomly assigned first to a persuasive message either against or in favor of the legalization, which they read with relatively high or low degrees of deliberative thinking. Attitudes and intentions regarding legalization were assessed following that message. Next, each participant received a second message that was opposed to the first one, serving as an attack against the attitude that participants had just formed. Finally, attitudes were again assessed. As hypothesized, participants showed greater attitude-consistent intentions when they formed their initial attitudes through thoughtful (vs. nonthoughtful) consideration of the first message. Moreover, the second message resulted in greater resistance to attitude change when participants formed their initial attitudes through thoughtful (vs. nonthoughtful) processes. PMID- 27385741 TI - Value of patient-reported symptoms in the diagnosis of transient loss of consciousness. AB - OBJECTIVE: Epileptic seizures, syncope, and psychogenic nonepileptic seizures (PNES) account for over 90% of presentations with transient loss of consciousness (TLOC). The patient's history is crucial for the diagnosis, but the diagnostic value of individual semiologic features is limited. This study explores the diagnostic potential of a comprehensive questionnaire focusing on TLOC-associated symptoms. METHODS: A total of 386 patients with proven epilepsy, 308 patients with proven PNES, and 371 patients with proven syncope were approached by post to recruit 100 patients in each diagnostic group. Symptoms were self-reported on an 86-item questionnaire (the Paroxysmal Event Profile [PEP]) using a 5-point Likert scale (always to never). Data were subjected to exploratory factor analysis (EFA) followed by confirmatory factor analysis (CFA). Factors were used to differentiate between diagnoses by pairwise and multinomial regression. RESULTS: Patients with PNES reported more and more frequent TLOC-associated symptoms than those with epilepsy or syncope (p < 0.001). EFA/CFA identified a 5-factor structure based on 74/86 questionnaire items with loadings >=0.4. Pairwise logistic regression analysis correctly classified 91% of patients with epilepsy vs those with syncope, 94% of those with PNES vs those with syncope, and 77% of those with epilepsy vs those with PNES. Multinomial logistic regression analysis yielded a similar pattern. CONCLUSIONS: Clusters of self-reported TLOC symptoms can be used to direct patients to appropriate investigation and treatment pathways for syncope on the one hand and seizures on the other, although additional information is required for a reliable distinction, especially between epilepsy and PNES. PMID- 27385742 TI - The diagnostic discrimination of cutaneous alpha-synuclein deposition in Parkinson disease. AB - OBJECTIVE: To determine the diagnostic discrimination of cutaneous alpha synuclein deposition in individuals with Parkinson disease (PD) with and without autonomic dysfunction on autonomic testing, in early and late stages of the disease, and of short and long duration. METHODS: Twenty-eight participants with PD and 23 control participants were studied by skin biopsies at multiple sites, autonomic function testing, and disease-specific scales. RESULTS: Skin biopsies provide >90% sensitivity and >90% specificity to distinguish PD from control participants across all biopsies sites with quantification of either pilomotor or sudomotor alpha-synuclein deposition. All individuals with PD have significantly higher cutaneous alpha-synuclein deposition than control participants, even those individuals with PD and no evidence of autonomic dysfunction. Deposition of alpha synuclein is most prominent in sympathetic adrenergic nerve fibers innervating the arrector pili muscles, but is also present in sudomotor (sympathetic cholinergic) nerve fibers. alpha-Synuclein is present even in the early stages of disease and disease of short duration. alpha-Synuclein ratios were higher in individuals with autonomic failure, with more advanced stages of disease and disease of longer duration. CONCLUSIONS: The alpha-synuclein ratio provides a sensitive and specific diagnostic biomarker of PD even in patients without autonomic failure. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that cutaneous alpha-synuclein deposition accurately identifies patients with PD. PMID- 27385743 TI - The origins and progression of CNS autoimmunity: Nature, nurture, and tumor. PMID- 27385745 TI - Spontaneous limb withdrawal heralding hyperacute stroke or stroke worsening. PMID- 27385744 TI - Type 2 diabetes mellitus is associated with brain atrophy and hypometabolism in the ADNI cohort. AB - OBJECTIVE: We investigated type 2 diabetes mellitus (T2DM) as a risk factor for brain atrophy and glucose hypometabolism in older adults with or at risk of cognitive impairment. METHODS: Participants with the T2DM were identified from the Alzheimer's Disease Neuroimaging Initiative (ADNI-1/GO/2 cohorts). Analysis of covariance models were used to compare participants with and without T2DM, controlling for potential confounding factors. RESULTS: Whole brain volume and whole brain [(18)F]-fluorodeoxyglucose (FDG) uptake were significantly different as a function of T2DM status, independent of baseline clinical diagnosis. On post hoc analysis, a lower whole brain volume was seen in participants with both mild cognitive impairment (MCI) and T2DM (n = 76) compared with participants who had MCI but not T2DM (n = 747; p = 0.009). Similarly, mean FDG uptake in gray matter and white matter was lower in participants with both MCI and T2DM (n = 72) than in participants with MCI without T2DM (n = 719; p = 0.04). Subsequent regional analysis revealed that the decreased FDG uptake in participants with both MCI and T2DM was mainly manifested in 3 brain regions: frontal lobe, sensory motor cortex, and striatum. CONCLUSIONS: T2DM may accelerate cognition deterioration in patients with MCI by affecting glucose metabolism and brain volume. PMID- 27385746 TI - Impaired self-agency in functional movement disorders: A resting-state fMRI study. AB - OBJECTIVE: To investigate the neural mechanisms underlying impaired self-agency in patients with functional movement disorders using resting-state functional MRI (fMRI). METHODS: We obtained resting-state fMRI on 35 patients with clinically definite functional movement disorders and 35 age- and sex-matched healthy controls. Between-group differences in functional connectivity from the right temporo-parietal junction (TPJ), a region previously demonstrated to play a critical role in self-agency by comparing internal predictions of movement with actual external events, were assessed using t tests. All participants were screened for psychiatric diagnoses using a structured clinical interview and completed the Beck Depression Inventory and Childhood Trauma Questionnaire. RESULTS: Compared to the healthy controls, patients with functional movement disorders showed decreased functional connectivity between the right TPJ and the right sensorimotor cortex, cerebellar vermis, bilateral supplementary motor area, and right insula. These findings were independent of depression, anxiety, and childhood trauma scores included in our assessment as covariates. CONCLUSIONS: The decreased functional connectivity between the right TPJ and bilateral sensorimotor regions observed in patients with functional movement disorders supports a model whereby impaired motor feed-forward together with altered sensory feedback from sensorimotor regions and areas of sensorimotor integration to the right TPJ contributes to patients' impaired sense of self-agency. PMID- 27385747 TI - Multiple sequential antibody-associated syndromes with a recurrent mutated neuroblastoma. PMID- 27385748 TI - New insights into the neural basis of functional movement disorders. PMID- 27385740 TI - Polygenic risk of Alzheimer disease is associated with early- and late-life processes. AB - OBJECTIVE: To examine associations between aggregate genetic risk and Alzheimer disease (AD) markers in stages preceding the clinical symptoms of dementia using data from 2 large observational cohort studies. METHODS: We computed polygenic risk scores (PGRS) using summary statistics from the International Genomics of Alzheimer's Project genome-wide association study of AD. Associations between PGRS and AD markers (cognitive decline, clinical progression, hippocampus volume, and beta-amyloid) were assessed within older participants with dementia. Associations between PGRS and hippocampus volume were additionally examined within healthy younger participants (age 18-35 years). RESULTS: Within participants without dementia, elevated PGRS was associated with worse memory (p = 0.002) and smaller hippocampus (p = 0.002) at baseline, as well as greater longitudinal cognitive decline (memory: p = 0.0005, executive function: p = 0.01) and clinical progression (p < 0.00001). High PGRS was associated with AD-like levels of beta-amyloid burden as measured with florbetapir PET (p = 0.03) but did not reach statistical significance for CSF beta-amyloid (p = 0.11). Within the younger group, higher PGRS was associated with smaller hippocampus volume (p = 0.05). This pattern was evident when examining a PGRS that included many loci below the genome-wide association study (GWAS)-level significance threshold (16,123 single nucleotide polymorphisms), but not when PGRS was restricted to GWAS-level significant loci (18 single nucleotide polymorphisms). CONCLUSIONS: Effects related to common genetic risk loci distributed throughout the genome are detectable among individuals without dementia. The influence of this genetic risk may begin in early life and make an individual more susceptible to cognitive impairment in late life. Future refinement of polygenic risk scores may help identify individuals at risk for AD dementia. PMID- 27385749 TI - Multiphase CT angiography increases detection of anterior circulation intracranial occlusion. AB - OBJECTIVE: To evaluate whether the use of multiphase CT angiography (CTA) improves interrater agreement for intracranial occlusion detection between stroke neurology trainees and an expert neuroradiologist. METHODS: A neuroradiologist and 2 stroke neurology fellows independently reviewed 100 prospectively collected single-phase and multiphase CTA scans from acute ischemic stroke patients with mild symptoms (NIH Stroke Scale score <=5). The presence and location of a vascular occlusion(s) were documented. Interrater agreement single- and multiphase CTA was quantified using unweighted kappa statistics. We assessed for any occlusions, anterior vs posterior occlusions, and pial vessel asymmetry. RESULTS: Using multiphase CTA, the neuroradiologist detected 50 scans with anterior circulation occlusions and 15 scans with posterior circulation occlusions. Median reading time was 2 minutes per scan. Median reading time for the neurologists was 3 minutes per multiphase CTA scan. Interrater agreement was fair between the 2 neurologists and neuroradiologist when using single-phase CTA (kappa = 0.45 and 0.32). Agreement improved minimally when stratified by anterior vs posterior circulation. When using multiphase CTA, agreement was high for detection of occlusion or asymmetry of pial vessels in the anterior circulation (kappa = 0.80 and 0.84). CONCLUSIONS: Multiphase CTA improves diagnostic accuracy in minor ischemic stroke for detection of anterior circulation intracranial occlusion. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that multiphase CTA, compared to single-phase CTA, improves the interrater agreement between stroke neurology trainees and an expert neuroradiologist for detecting anterior circulation intracranial vascular occlusion in patients with minor acute ischemic strokes. PMID- 27385751 TI - Professor Robert McNeill Alexander CBE FRS (1934-2016). AB - Robert McNeill Alexander, known to friends and colleagues as 'Neill', was a zoologist with an engineer's eye for how animals work. He used mathematical models to show how evolution has produced optimal designs. His skill was to choose appropriate models: realistic enough to contain the essence of a problem and yet simple enough to be tractable. He wrote fluently and easily: 23 books, 280 papers and a CD-ROM entitled How Animals Move. PMID- 27385750 TI - Quantitative strength testing in ALS clinical trials. AB - OBJECTIVE: To study the attributes of quantitative strength testing using hand held dynamometry (HHD) as an efficacy measure in 2 large phase 3 amyotrophic lateral sclerosis (ALS) trials. METHODS: In the phase 3 trials of ceftriaxone and dexpramipexole, 513 and 943 patients, respectively, were enrolled in double blind, randomized, placebo-controlled trials with planned follow-up of at least 1 year. Patients were studied every 3 months in the ceftriaxone study and every 2 months in the dexpramipexole study. Evaluators of HHD were trained and had to show evidence of adequate performance of strength testing; the testing paradigm involved testing 9 muscle groups in the upper and lower extremity bilaterally. Neither drug significantly affected any outcome measure. Strength measurements were evaluated by individual muscle and by megascores, which averaged scaled strength measures to produce an overall measure of muscle strength. RESULTS: A measure combining rate of decline with both within- and between-patient variabilities of measurement, the coefficient of variation for rate of change, was calculated, and showed that HHD overall performed slightly less well than Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) but better than vital capacity. Individual muscles were highly correlated to the identical muscles on the contralateral side, as well as to other muscles in the same body region. Strength decline was correlated both with ALSFRS-R and vital capacity. CONCLUSION: Quantitative strength testing using HHD is a reliable and reproducible measure of decline in ALS. PMID- 27385752 TI - The temperature dependence of electrical excitability in fish hearts. AB - Environmental temperature has pervasive effects on the rate of life processes in ectothermic animals. Animal performance is affected by temperature, but there are finite thermal limits for vital body functions, including contraction of the heart. This Review discusses the electrical excitation that initiates and controls the rate and rhythm of fish cardiac contraction and is therefore a central factor in the temperature-dependent modulation of fish cardiac function. The control of cardiac electrical excitability should be sensitive enough to respond to temperature changes but simultaneously robust enough to protect against cardiac arrhythmia; therefore, the thermal resilience and plasticity of electrical excitation are physiological qualities that may affect the ability of fishes to adjust to climate change. Acute changes in temperature alter the frequency of the heartbeat and the duration of atrial and ventricular action potentials (APs). Prolonged exposure to new thermal conditions induces compensatory changes in ion channel expression and function, which usually partially alleviate the direct effects of temperature on cardiac APs and heart rate. The most heat-sensitive molecular components contributing to the electrical excitation of the fish heart seem to be Na(+) channels, which may set the upper thermal limit for the cardiac excitability by compromising the initiation of the cardiac AP at high temperatures. In cardiac and other excitable cells, the different temperature dependencies of the outward K(+) current and inward Na(+) current may compromise electrical excitability at temperature extremes, a hypothesis termed the temperature-dependent depression of electrical excitation. PMID- 27385753 TI - Lubricating the swordfish head. AB - The swordfish is reputedly the fastest swimmer on Earth. The concave head and iconic sword are unique characteristics, but how they contribute to its speed is still unknown. Recent computed tomography scans revealed a poorly mineralised area near the base of the rostrum. Here we report, using magnetic resonance imaging and electron microscopy scanning, the discovery of a complex organ consisting of an oil-producing gland connected to capillaries that communicate with oil-excreting pores in the skin of the head. The capillary vessels transport oil to abundant tiny circular pores that are surrounded by denticles. The oil is distributed from the pores over the front part of the head. The oil inside the gland is identical to that found on the skin and is a mixture of methyl esters. We hypothesize that the oil layer, in combination with the denticles, creates a super-hydrophobic layer that reduces streamwise friction drag and increases swimming efficiency. PMID- 27385754 TI - Altitude matters: differences in cardiovascular and respiratory responses to hypoxia in bar-headed geese reared at high and low altitudes. AB - Bar-headed geese (Anser indicus) fly at high altitudes during their migration across the Himalayas and Tibetan plateau. However, we know relatively little about whether rearing at high altitude (i.e. phenotypic plasticity) facilitates this impressive feat because most of what is known about their physiology comes from studies performed at sea level. To provide this information, a comprehensive analysis of metabolic, cardiovascular and ventilatory responses to progressive decreases in the equivalent fractional composition of inspired oxygen (FiO2 : 0.21, 0.12, 0.09, 0.07 and 0.05) was made on bar-headed geese reared at either high altitude (3200 m) or low altitude (0 m) and on barnacle geese (Branta leucopsis), a low-altitude migrating species, reared at low altitude (0 m). Bar headed geese reared at high altitude exhibited lower metabolic rates and a modestly increased hypoxic ventilatory response compared with low-altitude-reared bar-headed geese. Although the in vivo oxygen equilibrium curves and blood-oxygen carrying capacity did not differ between the two bar-headed goose study groups, the blood-oxygen carrying capacity was higher than that of barnacle geese. Resting cardiac output also did not differ between groups and increased at least twofold during progressive hypoxia, initially as a result of increases in stroke volume. However, cardiac output increased at a higher FiO2 threshold in bar headed geese raised at high altitude. Thus, bar-headed geese reared at high altitude exhibited a reduced oxygen demand at rest and a modest but significant increase in oxygen uptake and delivery during progressive hypoxia compared with bar-headed geese reared at low altitude. PMID- 27385755 TI - Jumping mechanisms and performance in beetles. I. Flea beetles (Coleoptera: Chrysomelidae: Alticini). AB - The present study analyses the anatomy, mechanics and functional morphology of the jumping apparatus, the performance and the kinematics of the natural jump of flea beetles (Coleoptera: Chrysomelidae: Galerucinae: Alticini). The kinematic parameters of the initial phase of the jump were calculated for five species from five genera (average values from minimum to maximum): acceleration 0.91-2.25 (*10(3)) m s(-2), velocity 1.48-2.80 m s(-1), time to take-off 1.35-2.25 ms, kinetic energy 2.43-16.5 uJ, G: -force 93-230. The jumping apparatus is localized in the hind legs and formed by the femur, tibia, femoro-tibial joint, modified metafemoral extensor tendon, extensor ligament, tibial flexor sclerite, and extensor and flexor muscles. The primary role of the metafemoral extensor tendon is seen in the formation of an increased attachment site for the extensor muscles. The rubber-like protein resilin was detected in the extensor ligament, i.e. a short, elastic element connecting the extensor tendon with the tibial base. The calculated specific joint power (max. 0.714 W g(-1)) of the femoro tibial joint during the jumping movement and the fast full extension of the hind tibia (1-3 ms) suggest that jumping is performed via a catapult mechanism releasing energy that has beforehand been stored in the extensor ligament during its stretching by the extensor muscles. In addition, the morphology of the femoro tibial joint suggests that the co-contraction of the flexor and the extensor muscles in the femur of the jumping leg is involved in this process. PMID- 27385756 TI - The significance of respiration timing in the energetics estimates of free ranging killer whales (Orcinus orca). AB - Respiration rate has been used as an indicator of metabolic rate and associated cost of transport (COT) of free-ranging cetaceans, discounting potential respiration-by-respiration variation in O2 uptake. To investigate the influence of respiration timing on O2 uptake, we developed a dynamic model of O2 exchange and storage. Individual respiration events were revealed from kinematic data from 10 adult Norwegian herring-feeding killer whales (Orcinus orca) recorded with high-resolution tags (DTAGs). We compared fixed O2 uptake per respiration models with O2 uptake per respiration estimated through a simple 'broken-stick' O2 uptake function, in which O2 uptake was assumed to be the maximum possible O2 uptake when stores are depleted or maximum total body O2 store minus existing O2 store when stores are close to saturated. In contrast to findings assuming fixed O2 uptake per respiration, uptake from the broken-stick model yielded a high correlation (r(2)>0.9) between O2 uptake and activity level. Moreover, we found that respiration intervals increased and became less variable at higher swimming speeds, possibly to increase O2 uptake efficiency per respiration. As found in previous studies, COT decreased monotonically versus speed using the fixed O2 uptake per respiration models. However, the broken-stick uptake model yielded a curvilinear COT curve with a clear minimum at typical swimming speeds of 1.7-2.4 m s(-1) Our results showed that respiration-by-respiration variation in O2 uptake is expected to be significant. And though O2 consumption measurements of COT for free-ranging cetaceans remain impractical, accounting for the influence of respiration timing on O2 uptake will lead to more consistent predictions of field metabolic rates than using respiration rate alone. PMID- 27385757 TI - Why vascular siphons with sub-atmospheric pressures are physiologically impossible in sauropod dinosaurs. PMID- 27385758 TI - Can giraffes be supersized? Response to 'Why vascular siphons with sub atmospheric pressures are physiologically impossible in sauropod dinosaurs'. PMID- 27385759 TI - A nicotinic acetylcholine receptor agonist affects honey bee sucrose responsiveness and decreases waggle dancing. PMID- 27385760 TI - Compared with Raw Bovine Meat, Boiling but Not Grilling, Barbecuing, or Roasting Decreases Protein Digestibility without Any Major Consequences for Intestinal Mucosa in Rats, although the Daily Ingestion of Bovine Meat Induces Histologic Modifications in the Colon. AB - BACKGROUND: Cooking may impair meat protein digestibility. When undigested proteins are fermented by the colon microbiota, they can generate compounds that potentially are harmful to the mucosa. OBJECTIVES: This study addressed the effects of typical cooking processes and the amount of bovine meat intake on the quantity of undigested proteins entering the colon, as well as their effects on the intestinal mucosa. METHODS: Male Wistar rats (n = 88) aged 8 wk were fed 11 different diets containing protein as 20% of energy. In 10 diets, bovine meat proteins represented 5% [low-meat diet (LMD)] or 15% [high-meat diet (HMD)] of energy, with the rest as total milk proteins. Meat was raw or cooked according to 4 processes (boiled, barbecued, grilled, or roasted). A meat-free diet contained only milk proteins. After 3 wk, rats ingested a (15)N-labeled meat meal and were killed 6 h later after receiving a (13)C-valine injection. Meat protein digestibility was determined from (15)N enrichments in intestinal contents. Cecal short- and branched-chain fatty acids and hydrogen sulfide were measured. Intestinal tissues were used for the assessment of protein synthesis rates, inflammation, and histopathology. RESULTS: Meat protein digestibility was lower in rats fed boiled meat (94.5% +/- 0.281%) than in the other 4 groups (97.5% +/- 0.0581%, P < 0.001). Cecal and colonic bacterial metabolites, inflammation indicators, and protein synthesis rates were not affected by cooking processes. The meat protein amount had a significant effect on cecal protein synthesis rates (LMD > HMD) and on myeloperoxidase activity in the proximal colon (HMD > LMD), but not on other outcomes. The ingestion of bovine meat, whatever the cooking process and the intake amount, resulted in discrete histologic modifications of the colon (epithelium abrasion, excessive mucus secretion, and inflammation). CONCLUSIONS: Boiling bovine meat at a high temperature (100 degrees C) for a long time (3 h) moderately lowered protein digestibility compared with raw meat and other cooking processes, but did not affect cecal bacterial metabolites related to protein fermentation. The daily ingestion of raw or cooked bovine meat had no marked effect on intestinal tissues, despite some slight histologic modifications on distal colon. PMID- 27385761 TI - Modest U-Shaped Association between Dietary Acid Load and Risk of All-Cause and Cardiovascular Mortality in Adults. AB - BACKGROUND: Conflicting evidence associates diet acidity with the incidence of chronic diseases such as hypertension, diabetes, kidney disease, and bone-mineral disorders. It is currently unknown whether dietary acidity is associated with death. OBJECTIVE: We investigated the association of dietary acid load with the risk of all-cause and cardiovascular disease (CVD) mortality. METHODS: We used data from 2 prospective cohorts, the Swedish Mammography Cohort and the Cohort of Swedish Men, which included 36,740 women and 44,957 men aged 45-84 y at the start of a 15-y follow-up period (1998-2012). Acid load was estimated from food frequency questionnaires by use of the validated potential renal acid load (PRAL) algorithm. Deaths were ascertained via record linkage. Associations of PRAL with mortality were modeled by use of restricted cubic splines. RESULTS: The median PRAL was 0.65 mEq/d (range: -109 to 81.5 mEq/d) in women and 12.3 mEq/d (-111 to 121 mEq/d) in men. During a mean of 13.5 +/- 3.3 y of follow-up, there were 8576 and 13,332 deaths, of which 3203 and 5427 were attributed to cardiovascular causes in woman and men, respectively. In both sexes, a nonlinear U-shaped relation was observed, with higher mortality rates for both dietary acid and alkali excess. Compared with neutral PRAL (0 mEq/d), the HRs for all-cause mortality for the 10th and 90th percentiles of PRAL were 1.05 (95% CI: 1.01, 1.10) and 1.03 (95% CI: 0.98, 1.08), respectively, in women. The corresponding results for men were HRs 1.01 (95% CI: 1.00, 1.02) and 1.04 (95% CI: 1.00, 1.08) respectively. This relation was slightly stronger for CVD mortality. CONCLUSIONS: Excess diet alkalinity and acidity both showed weak associations with higher mortality in Swedish adults. An acid-base balanced diet was associated with the lowest mortality, but the magnitude of mortality reduction was modest. The Swedish Mammography Cohort was registered at clinicaltrials.gov as NCT01127698 The Cohort of Swedish Men was registered at clinicaltrials.gov as NCT01127711. PMID- 27385764 TI - Dietary Supplementation with alpha-Ketoglutarate Activates mTOR Signaling and Enhances Energy Status in Skeletal Muscle of Lipopolysaccharide-Challenged Piglets. AB - BACKGROUND: Skeletal muscle undergoes rapid loss in response to inflammation. alpha-Ketoglutarate (AKG) has been reported to enhance muscle growth in piglets, but the underlying mechanisms are largely unknown. OBJECTIVES: This study tested the hypothesis that dietary AKG supplementation activates mechanistic target of rapamycin (mTOR) signaling and improves skeletal muscle energy metabolism in lipopolysaccharide (LPS)-challenged piglets. METHODS: Forty-eight male piglets (Duroc * Landrace * Yorkshire) were weaned at 21 d of age to a corn- and soybean meal-based diet. After a 3-d period of adaptation, piglets with a mean weight of 7.21 kg were randomly assigned to control, LPS (intraperitoneal administration of 80 MUg LPS/kg body weight on days 10, 12, 14, and 16), or LPS plus 1% dietary AKG (LPS+AKG) groups. On day 16, blood samples were collected from 8 piglets/group 3 h after LPS administration. On day 17, piglets were killed to obtain gastrocnemius muscle from 8 piglets/group for biochemical analysis. RESULTS: Compared with the control group, LPS administration increased (P < 0.05) plasma concentrations of globulin (by 14%) and tumor necrosis factor alpha (by 59%) and the intramuscular ratio of AMP to ATP (by 93%) and abundance of phosphorylated acetyl-coenzyme A carboxylase (ACC) beta protein (by 64%). Compared with the control group, LPS administration reduced (P < 0.05) weight gain (by 15%); plasma concentrations of glutamine (by 20%), glucose (by 23%), insulin, insulin-like growth factor I, and epidermal growth factor; intramuscular concentrations of glutamine (by 27%), ATP (by 12%), ADP (by 22%), and total adenine nucleotides; and intramuscular ratios of phosphorylated mTOR to total mTOR (by 38%) and of phosphorylated 70-kDa ribosomal protein S6 kinase (p70S6K) to total p70S6K (by 39%). These adverse effects of LPS were ameliorated (P < 0.05) by AKG supplementation. CONCLUSIONS: Dietary AKG supplementation activated mTOR signaling, inhibited ACC-beta, and improved energy status in skeletal muscle of LPS-challenged piglets. These results provide a biochemical basis for the use of AKG to enhance piglet growth under inflammatory or practical postweaning conditions. PMID- 27385765 TI - Nevin Stewart Scrimshaw, PhD, MD, MPH (1918-2013). PMID- 27385762 TI - Tissue Concentrations of Vitamin K and Expression of Key Enzymes of Vitamin K Metabolism Are Influenced by Sex and Diet but Not Housing in C57Bl6 Mice. AB - BACKGROUND: There has been limited characterization of biological variables that impact vitamin K metabolism. This gap in knowledge can limit the translation of data obtained from preclinical animal studies to future human studies. OBJECTIVE: The purpose of this study was to determine the effects of diet, sex, and housing on serum, tissue, and fecal vitamin K concentrations and gene expression in C57BL6 mice during dietary vitamin K manipulation. METHODS: C57BL6 4-mo-old male and female mice were randomly assigned to conventional or suspended-wire cages and fed control [1400 +/- 80 MUg phylloquinone (PK)/kg] or deficient (31 +/- 0.45 MUg PK/kg) diets for 28 d in a factorial design. PK and menaquinone (MK) 4 plasma and tissue concentrations were measured by HPLC. Long-chain MKs were measured in all matrices by LC-atmospheric pressure chemical ionization-mass spectrometry. Gene expression was quantified by reverse transcriptase-polymerase chain reaction in the liver, brain, kidney, pancreas, and adipose tissue. RESULTS: Male and female mice responded differently to dietary manipulation in a tissue-dependent manner. In mice fed the control diet, females had ~3-fold more MK4 in the brain and mesenteric adipose tissue than did males and 100% greater PK concentrations in the liver, kidney, and mesenteric adipose tissue than did males. In mice fed the deficient diet, kidney MK4 concentrations were ~4-fold greater in females than in males, and there were no differences in other tissues. Males and females differed in the expression of vitamin K expoxide reductase complex 1 (Vkorc1) in mesenteric adipose tissue and the pancreas and ubiA domain-containing protein 1 (Ubiad1) in the kidney and brain. There was no effect of housing on serum, tissue, or fecal concentrations of any vitamin K form. CONCLUSIONS: Vitamin K concentrations and expression of key metabolic enzymes differ between male and female mice and in response to the dietary PK concentration. Identifying factors that may impact study design and outcomes of interest is critical to optimize study parameters examining vitamin K metabolism in animal models. PMID- 27385763 TI - Maternal Macronutrient Intake during Pregnancy Is Associated with Neonatal Abdominal Adiposity: The Growing Up in Singapore Towards healthy Outcomes (GUSTO) Study. AB - BACKGROUND: Infant body composition has been associated with later metabolic disease risk, but few studies have examined the association between maternal macronutrient intake and neonatal body composition. Furthermore, most of those studies have used proxy measures of body composition that may not reflect body fat distribution, particularly abdominal internal adiposity. OBJECTIVE: We investigated the relation between maternal macronutrient intake and neonatal abdominal adiposity measured by using MRI in a multiethnic Asian mother-offspring cohort. METHODS: The macronutrient intake of mothers was ascertained by using a 24-h dietary recall at 26-28 wk gestation. Neonatal abdominal adiposity was assessed by using MRI in week 2 of life. Mother-offspring dyads with complete macronutrient intake and adiposity information (n = 320) were included in the analysis. Associations were assessed by both substitution and addition models with the use of multivariable linear regressions. RESULTS: Mothers (mean age: 30 y) consumed (mean +/- SD) 15.5% +/- 4.3% of their energy from protein, 32.4% +/- 7.7% from fat, and 52.1% +/- 9.0% from carbohydrate. A higher-protein, lower carbohydrate or -fat diet during pregnancy was associated with lower abdominal internal adipose tissue (IAT) in the neonates [beta (95% CI): -0.18 mL (-0.35, 0.001 mL) per 1% protein-to-carbohydrate substitution and -0.25 mL (-0.46, -0.04 mL) per 1% protein-to-fat substitution]. These associations were stronger in boys than in girls (P-interaction < 0.05). Higher maternal intake of animal protein, but not plant protein, was associated with lower offspring IAT. In contrast, maternal macronutrient intake was not associated consistently with infant anthropometric measurements, including abdominal circumference and subscapular skinfold thickness. CONCLUSIONS: Higher maternal protein intake at the expense of carbohydrate or fat intake at 26-28 wk gestation was associated with lower abdominal internal adiposity in neonates. Optimizing maternal dietary balance might be a new approach to improve offspring body composition. This trial was registered at clinicaltrials.gov as NCT01174875. PMID- 27385766 TI - Protein N-terminal acetylation is required for embryogenesis in Arabidopsis. AB - Early embryonic development generates precursors of all major cell types in Arabidopsis. Among these precursors, the hypophysis divides asymmetrically to form the progenitors of the quiescent center and columella stem cells. A great deal has been learnt about the mechanisms that control the asymmetric division of the hypophysis and embryogenesis at the transcriptional level; however, no evidence of regulation at the co- or post-translational level has been reported. Here, we show that mutation of the catalytic subunit (Naa10) or auxiliary subunit (Naa15) of NatA, an N-terminal acetyltransferase that catalyzes protein N terminal acetylation, produces an embryo-lethal phenotype. In addition, Naa10 and Naa15 were found to interact physically in planta Further analysis revealed that the observed embryonic patterning defects started at the early globular stage and that the asymmetric division of the hypophysis was irregular; thus, no quiescent center progenitor cells were generated in naa10 and naa15 embryos. We further observed that the polar distributions of auxin and its efflux carrier PIN1 were disturbed in naa10 embryos. Our results suggest that NatA is required for asymmetric division of the hypophysis and early embryonic patterning in Arabidopsis, and provides a link between protein N-terminal acetylation and embryogenesis in plants. PMID- 27385768 TI - Declines in the diagnosis of primary progressive MS: A critical change in phenotype or critical measurement error? PMID- 27385767 TI - Cadmium accumulation is enhanced by ammonium compared to nitrate in two hyperaccumulators, without affecting speciation. AB - Nitrogen fertilization could improve the efficiency of Cd phytoextraction in contaminated soil and thus shorten the remediation time. However, limited information is available on the effect of N form on Cd phytoextraction and associated mechanisms in plants. This study examined the effect of N form on Cd accumulation, translocation, and speciation in Carpobrotus rossii and Solanum nigrum Plants were grown in nutrient solution with 5-15 MUM Cd in the presence of 1000 uM NH4 (+) or NO3 (-) Plant growth and Cd uptake were measured, and Cd speciation was analyzed using synchrotron-based X-ray absorption spectroscopy. Shoot Cd accumulation was 30% greater with NH4 (+) than NO3 (-) supply. Carpobrotus rossii accumulated three times more Cd than S. nigrum. However, Cd speciation in the plants was not influenced by N form, but it did vary with species and tissues. In C. rossii, up to 91% of Cd was bound to S-containing ligands in all tissues except the xylem sap where 87-95% were Cd-OH complexes. Furthermore, the proportion of Cd-S in shoots was substantially lower in S. nigrum (44-69%) than in C. rossii (60-91%). It is concluded that the application of NH4 (+) (instead of NO3 (-)) increased shoot Cd accumulation by increasing uptake and translocation, rather than changing Cd speciation, and is potentially an effective approach for increasing Cd phytoextraction. PMID- 27385769 TI - Factors associated with suicides in Wolverhampton: Relevance of local audits exploring preventability. AB - Suicide rates and associated risk factors are known to change over time. The periodic evaluation of suicides in a particular locality may identify specific issues that may help in prevention efforts. The profile of 146 consecutive cases with suicide, open and narrative verdicts between January 2004 and July 2011 in Wolverhampton was studied in order to explore associated factors. Specific information about methods, mental health issues and stressors was collected. There was considerable variation in suicides in different wards of the city, with higher occurrences in inner-city areas. Male suicides were three times more common, and they were significantly younger than in female suicides. Common methods were hanging (52.7%) and poisoning (21.9%) involving a wide range of drugs. Life events were reported in 52.1% suicides, most frequently relational problems (28.1%), followed by physical illness and bereavement. Mental-health factors were associated with 63.0% of suicides, predominantly depression (45.9%) and alcohol and drug abuse (6.8%). The majority of the suicide victims (63.0%) were not in contact with mental-health services, including: most men (68.8%), young suicides up to age 34 (78.6%), the elderly (69.2%) and Asians (70.0%). A considerable proportion of these suicides had mental-health issues, mainly depression (42.4%) and alcohol or drug abuse (6.5%). Significantly more of them (69.6% vs. 22.2%) had stressors compared with suicides known to mental-health services. The findings of the study highlighted risk factors that may help prioritising intervention initiatives. It appears that local suicide audits may complement national information on suicide in designing appropriate local suicide prevention strategies. PMID- 27385770 TI - Spinal Infections Among Patients With Long-Term Central Venous Catheters for Home Parenteral Nutrition. AB - Spinal infections are a rare yet serious metastatic complication of bacteremia among patients with long-term central venous catheters (CVCs) for which clinicians must remain vigilant. We performed a retrospective review of all cases of spinal infection occurring in the context of a CVC for long-term parenteral nutrition (PN) managed in our department between January 2010 and October 2013, a cohort of 310 patients over this time period. Six patients were identified (mean age, 65 years; 5 male). One hundred percent of patients presented with spinal pain (5/6 cervical, 1/6 thoracic). Organisms were cultured from the CVC in 5 of 6 patients. In all cases, the white blood cell count was normal, and in 5 of 6, C reactive protein was normal. All diagnoses were confirmed on magnetic resonance imaging (MRI), and in 3 of 6 cases, an MRI was repeated (on the advice of neurosurgical colleagues) to confirm resolution of changes after a period of antimicrobial therapy. There was no clear correlation between duration of PN or number of days following CVC insertion and onset of infection. The CVC was replaced in 4 of 6 patients at the time of diagnosis, delayed removal in 1 of 6, and salvaged in the remaining case. Although rare, a high index of suspicion is needed in patients receiving long-term PN who present with spinal pain. Peripheral inflammatory markers may not be elevated. MRI should be performed and patients should be treated with antibiotics alongside involvement of local microbiology and neurosurgical teams. Multidisciplinary discussion on CVC salvage in these cases is important, especially in cases of challenging vascular anatomy. PMID- 27385771 TI - Orchid conservation: further links. AB - BACKGROUND: Due in great part to their often complex interactions with mycorrhizal fungi, pollinators and host trees, Orchidaceae present particular challenges for conservation. Furthermore, orchids, as potentially the largest family of angiosperms with >26000 species, species complexes and frequent hybrid formation, are complex to catalogue. Following a highlight in 2015, a further seven papers focusing on orchids, their interactions with beneficial organisms, pollinators and mycorrhiza, and other factors relating to their conservation, including threats from human utilization and changing land use, are presented here. CONCLUSIONS: The production of an online flora of all known plants and an assessment of the conservation status of all known plant species as far as possible, to guide conservation action are the first two targets of the Global Strategy for Plant Conservation Without knowing how many species there are and how they should be circumscribed, neither of these targets is achievable. Orchids are a fascinating subject for fundamental research with rapid species evolution, specific organ structure and development, but they also suffer from high levels of threat. Effective orchid conservation must take account of the beneficial interactions with fungi and pollinators and the potentially detrimental effects of over-collection and changes in land use. PMID- 27385774 TI - Density measurements with computed tomography in patients with extra-axial hematoma can quantitatively estimate a degree of brain compression. AB - BACKGROUND: Extra-axial hematoma can cause significant brain compression. Guidelines for surgical evacuation include imaging findings (midline shift and hematoma thickness/volume) in conjunction with Glasgow Coma Scale (GCS) scores and/or intracranial pressure (ICP) monitoring. Physiologically, overall brain density should also change with compression. In our observational study, we explored whether overall brain density, defined using computed tomography Hounsfield Units (CT HU), changes after surgical evacuation of extra-axial hematoma. METHODS AND MATERIALS: Only patients with a surgical acute epidural hematoma or subacute/chronic subdural hematoma were considered. Other exclusion criteria were concurrent intraparenchymal pathology, bilateral pathology, or incomplete follow-up imaging. Between fall 2012 and spring 2015, 22 patients were included in the study. CT head imaging (preoperative, postoperative, and at ~1- to 2-month clinic visit) were loaded into OsiriX (Pixmeo, Switzerland). All the intracranial regions were selected and all extra-axial features were removed; subsequently, software was used to calculate a global CT HU value. RESULTS: A repeated-measures ANOVA found significant time effect, p < 0.01, with significance between preoperative versus postoperative CT (p = 0.03) and preoperative versus clinic visit CT (p < 0.01). CONCLUSION: The results from this study suggest that extra-axial hematomas, which deform the brain, can cause an elevation in global CT HU value; moreover, surgical decompression is associated with lower global CT HU values. The use of global CT HU values in selected populations may serve as an adjunct for the evaluation of surgical lesions. PMID- 27385775 TI - Fluctuating locked-in syndrome as a presentation of a bilateral pontine infarction. AB - The "pontine warning syndrome" is characterized by recurrent episodes of motor hemiparesis, dysarthria and horizontal gaze palsy associated with basilar artery branch infarction. We report a case of a patient who presented with recurrent, self-limited episodes of locked-in syndrome, related to a bilateral pontine infarction. As far as we know, this clinical presentation as a subtype of pontine warning syndrome has never been described. We discuss the case, the differential diagnosis of the neuroimaging and the possible underlying mechanism. PMID- 27385776 TI - Whole Body Vibration Exposures and Health Status among Professional Truck Drivers: A Cross-sectional Analysis. AB - Many professional truck drivers suffer from low back pain (LBP) which is thought to be associated with exposure to whole-body vibration (WBV). The objectives of this study were to: (i) characterize general health, regional body pain and WBV exposures, (ii) evaluate the associations between different WBV parameters and health outcomes, and (iii) determine whether there were factors which affect a truck driver's WBV exposures. This study analyzed WBV exposures from 96 long-haul truck drivers over their regular work shift (6-15h) per International Standards Organization (ISO) 2631-1 and 2631-5 WBV standards. This study also evaluated regional body pain (10-point scale), low back disability (the Oswestry Disability Index), and physical and mental health (the Short Form 12-item Health Survey). The results demonstrated that the daily vector sum WBV exposures [A(8), VDV(8) and Sed(8)] were above action limits while the predominant z-axis exposures were below action limits. Among all the musculoskeletal outcomes, LBP was the most prevalent (72.5%) with average LBP score of 2.9 (SD: 2.0). The SF-12 health scores demonstrated that truck drivers in general had lower physical health status than the general US population (P's < 0.04) and that physical health status decreased as WBV exposures increased (P = 0.03). In addition, the correlations between the WBV measures and health outcomes indicated that A(8) exposure measures had a stronger link to musculoskeletal (LBP) and other health outcomes than the VDV(8) and Sed(8) measures. Finally, seat manufacturer and seat age were two factors which had a strong influence on WBV exposures. PMID- 27385777 TI - Lineage-Specific Effector Signatures of Invariant NKT Cells Are Shared amongst gammadelta T, Innate Lymphoid, and Th Cells. AB - Invariant NKT cells differentiate into three predominant effector lineages in the steady state. To understand these lineages, we sorted undifferentiated invariant NK T progenitor cells and each effector population and analyzed their transcriptional profiles by RNAseq. Bioinformatic comparisons were made to effector subsets among other lymphocytes, specifically Th cells, innate lymphoid cells (ILC), and gammadelta T cells. Myc-associated signature genes were enriched in NKT progenitors, like in other hematopoietic progenitors. Only NKT1 cells, but not NKT2 and NKT17 cells, had transcriptome similarity to NK cells and were also similar to other IFN-gamma-producing lineages such as Th1, ILC1, and intraepithelial gammadelta T cells. NKT2 and NKT17 cells were similar to their analogous subsets of gammadelta T cells and ILCs, but surprisingly, not to Th2 and Th17 cells. We identified a set of genes common to each effector lineage regardless of Ag receptor specificity, suggesting the use of conserved regulatory cores for effector function. PMID- 27385778 TI - Active Caspase-1 Induces Plasma Membrane Pores That Precede Pyroptotic Lysis and Are Blocked by Lanthanides. AB - Canonical inflammasome activation induces a caspase-1/gasdermin D (Gsdmd) dependent lytic cell death called pyroptosis that promotes antimicrobial host defense but may contribute to sepsis. The nature of the caspase-1-dependent change in plasma membrane (PM) permeability during pyroptotic progression remains incompletely defined. We assayed propidium(2+) (Pro(2+)) influx kinetics during NLRP3 or Pyrin inflammasome activation in murine bone marrow-derived macrophages (BMDMs) as an indicator of this PM permeabilization. BMDMs were characterized by rapid Pro(2+) influx after initiation of NLRP3 or Pyrin inflammasomes by nigericin (NG) or Clostridium difficile toxin B (TcdB), respectively. No Pro(2+) uptake in response to NG or TcdB was observed in Casp1(-/-) or Asc(-/-) BMDMs. The cytoprotectant glycine profoundly suppressed NG and TcdB-induced lysis but not Pro(2+) influx. The absence of Gsdmd expression resulted in suppression of NG stimulated Pro(2+) influx and pyroptotic lysis. Extracellular La(3+) and Gd(3+) rapidly and reversibly blocked the induced Pro(2+) influx and markedly delayed pyroptotic lysis without limiting upstream inflammasome assembly and caspase-1 activation. Thus, caspase-1-driven pyroptosis requires induction of initial prelytic pores in the PM that are dependent on Gsdmd expression. These PM pores also facilitated the efflux of cytosolic ATP and influx of extracellular Ca(2+) Although lanthanides and Gsdmd deletion both suppressed PM pore activity and pyroptotic lysis, robust IL-1beta release was observed in lanthanide-treated BMDMs but not in Gsdmd-deficient cells. This suggests roles for Gsdmd in both passive IL-1beta release secondary to pyroptotic lysis and in nonlytic/nonclassical IL-1beta export. PMID- 27385779 TI - A Critical Role for CD200R Signaling in Limiting the Growth and Metastasis of CD200+ Melanoma. AB - CD200 is a cell surface glycoprotein that functions through engaging CD200R on cells of the myeloid lineage and inhibits their functions. Expression of CD200 was implicated in a variety of human cancer cells, including melanoma cells; however, its roles in tumor growth and immunity are not clearly understood. In this study, we used CD200R-deficient mice and the B16 tumor model to evaluate this issue. We found that CD200R-deficient mice exhibited accelerated growth of CD200(+), but not CD200(-), B16 tumors. Strikingly, CD200R-deficient mice receiving CD200(+) B16 cells i.v. exhibited massive tumor growth in multiple organs, including liver, lung, kidney, and peritoneal cavity, whereas the growth of the same tumors in wild-type mice was limited. CD200(+) tumors grown in CD200R deficient mice contained higher numbers of CD11b(+)Ly6C(+) myeloid cells, exhibited increased expression of VEGF and HIF1alpha genes with increased angiogenesis, and showed significantly reduced infiltration of CD4(+) and CD8(+) T cells, presumably as the result of reduced expression of T cell chemokines, such as CXCL9 and CXCL16. The liver from CD200R-deficient mice, under metastatic growth of CD200(+) tumors, contained significantly increased numbers of CD11b(+)Gr1(-) myeloid cells and Foxp3(+) regulatory T cells and reduced numbers of NK cells. Liver T cells also had a reduced capacity to produce IFN-gamma or TNF-alpha. Taken together, we revealed a critical role for CD200R signaling in limiting the growth and metastasis of CD200(+) tumors. Thus, targeting CD200R signaling may potentially interfere with the metastatic growth of CD200(+) tumors, like melanoma. PMID- 27385780 TI - Protein Translation Activity: A New Measure of Host Immune Cell Activation. AB - We describe the in vivo ribopuromycylation (RPM) method, which uses a puromycin specific Ab to fluorescently label ribosome-bound puromycylated nascent chains, enabling measurement of translational activity via immunohistochemistry or flow cytometry. Tissue staining provides a unique view of virus-induced activation of adaptive, innate, and stromal immune cells. RPM flow precisely quantitates virus induced activation of lymphocytes and innate immune cells, and it provides a unique measure of immune cell deactivation and quiescence. Using RPM we find that high endothelial cells in draining lymph nodes rapidly increase translation in the first day of vaccinia virus infection. We also find a population of constitutively activated splenic T cells in naive mice and further that most bone marrow T cells activate 3 d after vaccinia virus infection. Bone marrow T cell activation is nonspecific, IL-12-dependent, and induces innate memory T cell phenotypic markers. Thus, RPM measures translational activity to uniquely identify cell populations that participate in the immune response to pathogens, other foreign substances, and autoantigens. PMID- 27385781 TI - Structure of the Adenovirus Type 4 (Species E) E3-19K/HLA-A2 Complex Reveals Species-Specific Features in MHC Class I Recognition. AB - Adenoviruses (Ads) subvert MHC class I Ag presentation and impair host anti-Ad cellular activities. Specifically, the Ad-encoded E3-19K immunomodulatory protein targets MHC class I molecules for retention within the endoplasmic reticulum of infected cells. We report the x-ray crystal structure of the Ad type 4 (Ad4) E3 19K of species E bound to HLA-A2 at 2.64-A resolution. Structural analysis shows that Ad4 E3-19K adopts a tertiary fold that is shared only with Ad2 E3-19K of species C. A comparative analysis of the Ad4 E3-19K/HLA-A2 structure with our x ray structure of Ad2 E3-19K/HLA-A2 identifies species-specific features in HLA-A2 recognition. Our analysis also reveals common binding characteristics that explain the promiscuous, and yet high-affinity, association of E3-19K proteins with HLA-A and HLA-B molecules. We also provide structural insights into why E3 19K proteins do not associate with HLA-C molecules. Overall, our study provides new information about how E3-19K proteins selectively engage with MHC class I to abrogate Ag presentation and counteract activation of CD8(+) T cells. The significance of MHC class I Ag presentation for controlling viral infections, as well as the threats of viral infections in immunocompromised patients, underline our efforts to characterize viral immunoevasins, such as E3-19K. PMID- 27385782 TI - Dimeric FcgammaR Ectodomains as Probes of the Fc Receptor Function of Anti Influenza Virus IgG. AB - Ab-dependent cellular cytotoxicity, phagocytosis, and Ag presentation are key mechanisms of action of Abs arising in vaccine or naturally acquired immunity, as well of therapeutic mAbs. Cells expressing the low-affinity FcgammaRs (FcgammaRII or CD32 and FcgammaRIII or CD16) are activated for these functions when receptors are aggregated following the binding of IgG-opsonized targets. Despite the diversity of the Fc receptor proteins, IgG ligands, and potential responding cell types, the induction of all FcgammaR-mediated responses by opsonized targets requires the presentation of multiple Fc regions in close proximity to each other. We demonstrated that such "near-neighbor" Fc regions can be detected using defined recombinant soluble (rs) dimeric low-affinity ectodomains (rsFcgammaR) that have an absolute binding requirement for the simultaneous engagement of two IgG Fc regions. Like cell surface-expressed FcgammaRs, the binding of dimeric rsFcgammaR ectodomains to Ab immune complexes was affected by Ab subclass, presentation, opsonization density, Fc fucosylation, or mutation. The activation of an NK cell line and primary NK cells by human IgG-opsonized influenza A hemagglutinin correlated with dimeric rsFcgammaRIIIa binding activity but not with Ab titer. Furthermore, the dimeric rsFcgammaR binding assay sensitively detected greater Fc receptor activity to pandemic H1N1 hemagglutinin after the swine influenza pandemic of 2009 in pooled human polyclonal IgG. Thus these dimeric rsFcgammaR ectodomains are validated, defined probes that should prove valuable in measuring the immune-activating capacity of IgG Abs elicited by infection or vaccination or experimentally derived IgG and its variants. PMID- 27385783 TI - Trophoblast Major Histocompatibility Complex Class I Expression Is Associated with Immune-Mediated Rejection of Bovine Fetuses Produced by Cloning. AB - Trophoblast cells from bovine somatic cell nuclear transfer (SCNT) conceptuses express major histocompatibility complex class I (MHC-I) proteins early in gestation, and this may be one cause of the significant first-trimester embryonic mortality observed in these pregnancies. MHC-I homozygous-compatible (n = 9), homozygous-incompatible (n = 8), and heterozygous-incompatible (n = 5) SCNT pregnancies were established. The control group consisted of eight pregnancies produced by artificial insemination. Uterine and placental samples were collected on Day 35 +/- 1 of pregnancy, and expression of MHC-I, leukocyte markers, and cytokines were examined by immunohistochemistry. Trophoblast cells from all SCNT pregnancies expressed MHC-I, while trophoblast cells from age-matched control pregnancies were negative for MHC-I expression. Expression of MHC-I antigens by trophoblast cells from SCNT pregnancies was associated with lymphocytic infiltration in the endometrium. Furthermore, MHC-I-incompatible conceptuses, particularly the heterozygous-incompatible ones, induced a more pronounced lymphocytic infiltration than MHC-I-compatible conceptuses. Cells expressing cluster of differentiation (CD) 3, gamma/deltaTCR, and MHC-II were increased in the endometrium of SCNT pregnancies compared to the control group. CD4(+) lymphocytes were increased in MHC-I-incompatible pregnancies compared to MHC-I compatible and control pregnancies. CD8(+), FOXP3(+), and natural killer cells were increased in MHC-I heterozygous-incompatible SCNT pregnancies compared to homozygous SCNT and control pregnancies. PMID- 27385785 TI - Improving the measurement of dielectric function by TEM-EELS: avoiding the retardation effect. AB - We investigated an improved Kramers-Kronig analysis (KKA) routine for measuring the dielectric function of alpha-Al2O3, avoiding the retardation effect arising in electron energy-loss spectroscopy (EELS). The EELS data differed from the optical data in the energy range of 10-20 eV due to the retardation effect, even though Cerenkov loss was thoroughly suppressed. The calculated differential cross section indicates that the influence of the retardation appears at scattering angles less than 0.2 mrad in the loss energy range of 10-15 eV. Using the improved KKA routine, we obtained the correct dielectric function that agreed with the optical data. The present technique is especially useful in measuring the dielectric function by EELS with a small collection semi-angle. PMID- 27385786 TI - Live correlative light-electron microscopy to observe molecular dynamics in high resolution. AB - Fluorescence microscopy (FM) is a powerful tool for observing specific molecular components in living cells, but its spatial resolution is relatively low. In contrast, electron microscopy (EM) provides high-resolution information about cellular structures, but it cannot provide temporal information in living cells. To achieve molecular selectivity in imaging at high resolution, a method combining EM imaging with live-cell fluorescence imaging, known as live correlative light-EM (CLEM), has been developed. In this method, living cells are first observed by FM, fixed in situ during the live observation and then subjected to EM observation. Various fluorescence techniques and tools can be applied for FM, resulting in the generation of various modified methods that are useful for understanding cellular structure in high resolution. Here, we review the methods of CLEM and live-cell imaging associated with CLEM (live CLEM). Such methods can greatly advance the understanding of the function of cellular structures on a molecular level, and thus are useful for medical fields as well as for basic biology. PMID- 27385784 TI - Prenatal Testosterone Exposure Decreases Aldosterone Production but Maintains Normal Plasma Volume and Increases Blood Pressure in Adult Female Rats. AB - Plasma testosterone levels are elevated in pregnant women with preeclampsia and polycystic ovaries; their offspring are at increased risk for hypertension during adult life. We tested the hypothesis that prenatal testosterone exposure induces dysregulation of the renin-angiotensin-aldosterone system, which is known to play an important role in water and electrolyte balance and blood pressure regulation. Female rats (6 mo old) prenatally exposed to testosterone were examined for adrenal expression of steroidogenic genes, telemetric blood pressure, blood volume and Na(+) and K(+) levels, plasma aldosterone, angiotensin II and vasopressin levels, and vascular responses to angiotensin II and arg(8) vasopressin. The levels of Cyp11b2 (aldosterone synthase), but not the other adrenal steroidogenic genes, were decreased in testosterone females. Accordingly, plasma aldosterone levels were lower in testosterone females. Plasma volume and serum and urine Na(+) and K(+) levels were not significantly different between control and testosterone females; however, prenatal testosterone exposure significantly increased plasma vasopressin and angiotensin II levels and arterial pressure in adult females. In testosterone females, mesenteric artery contractile responses to angiotensin II were significantly greater, while contractile responses to vasopressin were unaffected. Angiotensin II type-1 receptor expression was increased, while angiotensin II type-2 receptor was decreased in testosterone arteries. These results suggest that prenatal testosterone exposure downregulates adrenal Cyp11b2 expression, leading to decreased plasma aldosterone levels. Elevated angiotensin II and vasopressin levels along with enhanced vascular responsiveness to angiotensin II may serve as an underlying mechanism to maintain plasma volume and Na(+) and K(+) levels and mediate hypertension in adult testosterone females. PMID- 27385787 TI - Follow-up review: recent progress in the development of super-resolution optical microscopy. AB - The advent of super-resolution microscopy brought a huge impact to various research fields ranging from the fundamental science to medical and industrial applications. The technological development is still ongoing with involving different scientific disciplines and often changing the standard of optical imaging. In this review, I would like to introduce the recent research progress in super-resolution microscopy as a follow-up for the featured issue in Microscopy (Vol. 64, No. 4, 2015) with discussions especially on the current trends and new directions in the technological development. PMID- 27385788 TI - Atomic resolved phase map of monolayer MoS2 retrieved by spherical aberration corrected transport of intensity equation. AB - An atomic resolution phase map, which enables us to observe charge distribution or magnetic properties at an atomic scale, has been pointed out to be retrieved by transport of intensity equation (TIE) when taking two atomic-resolved transmission electron microscope (TEM) images of small defocus difference. In this work, we firstly obtained the atomic-resolved phase maps of an exfoliated molybdenum disulfide sheet using spherical aberration-corrected transmission electron microscope. We successfully observed 60 degrees grain boundary of mechanically exfoliated monolayer molybdenum disulfide sheet. The relative phase shift of a single molybdenum atomic column to the column consisting of two sulfur atoms was obtained to be about 0.01 rad on average, which was about half lower than the simulated TIE phase map, indicating that the individual atomic sites can be distinguished qualitatively. The appropriate condition for retrieving atomic resolved TIE phase maps was briefly discussed. PMID- 27385789 TI - Lymphovenous hemostasis and the role of platelets in regulating lymphatic flow and lymphatic vessel maturation. AB - Aside from the established role for platelets in regulating hemostasis and thrombosis, recent research has revealed a discrete role for platelets in the separation of the blood and lymphatic vascular systems. Platelets are activated by interaction with lymphatic endothelial cells at the lymphovenous junction, the site in the body where the lymphatic system drains into the blood vascular system, resulting in a platelet plug that, with the lymphovenous valve, prevents blood from entering the lymphatic circulation. This process, known as "lymphovenous hemostasis," is mediated by activation of platelet CLEC-2 receptors by the transmembrane ligand podoplanin expressed by lymphatic endothelial cells. Lymphovenous hemostasis is required for normal lymph flow, and mice deficient in lymphovenous hemostasis exhibit lymphedema and sometimes chylothorax phenotypes indicative of lymphatic insufficiency. Unexpectedly, the loss of lymph flow in these mice causes defects in maturation of collecting lymphatic vessels and lymphatic valve formation, uncovering an important role for fluid flow in driving endothelial cell signaling during development of collecting lymphatics. This article summarizes the current understanding of lymphovenous hemostasis and its effect on lymphatic vessel maturation and synthesizes the outstanding questions in the field, with relationship to human disease. PMID- 27385790 TI - Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia. AB - Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm with variable clinical course. To predict the clinical outcome, we previously developed a CMML-specific prognostic scoring system (CPSS) based on clinical parameters and cytogenetics. In this work, we tested the hypothesis that accounting for gene mutations would further improve risk stratification of CMML patients. We therefore sequenced 38 genes to explore the role of somatic mutations in disease phenotype and clinical outcome. Overall, 199 of 214 (93%) CMML patients carried at least 1 somatic mutation. Stepwise linear regression models showed that these mutations accounted for 15% to 24% of variability of clinical phenotype. Based on multivariable Cox regression analyses, cytogenetic abnormalities and mutations in RUNX1, NRAS, SETBP1, and ASXL1 were independently associated with overall survival (OS). Using these parameters, we defined a genetic score that identified 4 categories with significantly different OS and cumulative incidence of leukemic evolution. In multivariable analyses, genetic score, red blood cell transfusion dependency, white blood cell count, and marrow blasts retained independent prognostic value. These parameters were included into a clinical/molecular CPSS (CPSS-Mol) model that identified 4 risk groups with markedly different median OS (from >144 to 18 months, hazard ratio [HR] = 2.69) and cumulative incidence of leukemic evolution (from 0% to 48% at 4 years, HR = 3.84) (P < .001). The CPSS-Mol fully retained its ability to risk stratify in an independent validation cohort of 260 CMML patients. In conclusion, integrating conventional parameters and gene mutations significantly improves risk stratification of CMML patients, providing a robust basis for clinical decision making and a reliable tool for clinical trials. PMID- 27385791 TI - Therapeutic regulatory T-cell adoptive transfer ameliorates established murine chronic GVHD in a CXCR5-dependent manner. AB - Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation. In cGVHD, alloreactive T cells and germinal center (GC) B cells often participate in GC reactions to produce pathogenic antibodies. Although regulatory T cells (Tregs) can inhibit GC reactions, Treg numbers are reduced in cGVHD, contributing to cGVHD pathogenesis. Here, we explored 2 means to increase Tregs in cGVHD: interleukin-2/monoclonal antibody (IL-2/mAb) complexes and donor Treg infusions. IL-2/mAb complexes given over 1 month were efficacious in expanding Tregs and treating established cGVHD in a multi-organ-system disease mouse model characterized by GC reactions, antibody deposition, and lung dysfunction. In an acute GVHD (aGVHD) model, IL 2/mAb complexes given for only 4 days resulted in rapid mortality, indicating IL 2/mAb complexes can drive conventional T-cell (Tcon)-mediated injury. In contrast, Treg infusions, which uniformly suppress aGVHD, increased Treg frequency and were effective in preventing the onset of, and treating, established cGVHD. Efficacy was dependent upon CXCR5-sufficient Tregs homing to, and inhibiting, GC reactions. These studies indicate that the infusion of Tregs, especially ones enriched for GC homing, may be desirable for cGVHD therapy. Although IL-2/mAb complexes can be efficacious in cGVHD, a cautious approach needs to be taken in settings in which aGVHD elements, and associated Tcon, are present. PMID- 27385792 TI - Presaccadic motion integration between current and future retinotopic locations of attended objects. AB - Object tracking across eye movements is thought to rely on presaccadic updating of attention between the object's current and its "remapped" location (i.e., the postsaccadic retinotopic location). We report evidence for a bifocal, presaccadic sampling between these two positions. While preparing a saccade, participants viewed four spatially separated random dot kinematograms, one of which was cued by a colored flash. They reported the direction of a coherent motion signal at the cued location while a second signal occurred simultaneously either at the cue's remapped location or at one of several control locations. Motion integration between the signals occurred only when the two motion signals were congruent and were shown at the cue and at its remapped location. This shows that the visual system integrates features between both the current and the future retinotopic locations of an attended object and that such presaccadic sampling is feature specific. PMID- 27385794 TI - Oculomotor inhibition covaries with conscious detection. AB - Saccadic eye movements occur frequently even during attempted fixation, but they halt momentarily when a new stimulus appears. Here, we demonstrate that this rapid, involuntary "oculomotor freezing" reflex is yoked to fluctuations in explicit visual perception. Human observers reported the presence or absence of a brief visual stimulus while we recorded microsaccades, small spontaneous eye movements. We found that microsaccades were reflexively inhibited if and only if the observer reported seeing the stimulus, even when none was present. By applying a novel Bayesian classification technique to patterns of microsaccades on individual trials, we were able to decode the reported state of perception more accurately than the state of the stimulus (present vs. absent). Moreover, explicit perceptual sensitivity and the oculomotor reflex were both susceptible to orientation-specific adaptation. The adaptation effects suggest that the freezing reflex is mediated by signals processed in the visual cortex before reaching oculomotor control centers rather than relying on a direct subcortical route, as some previous research has suggested. We conclude that the reflexive inhibition of microsaccades immediately and inadvertently reveals when the observer becomes aware of a change in the environment. By providing an objective measure of conscious perceptual detection that does not require explicit reports, this finding opens doors to clinical applications and further investigations of perceptual awareness. PMID- 27385795 TI - Representing multiple object weights: competing priors and sensorimotor memories. AB - When lifting an object, individuals scale lifting forces based on long-term priors relating external object properties (such as material and size) to object weight. When experiencing objects that are poorly predicted by priors, people rapidly form and update sensorimotor memories that can be used to predict an object's atypical size-weight relation in support of predictively scaling lift forces. With extensive experience in lifting such objects, long-term priors, assessed with weight judgments, are gradually updated. The aim of the present study was to understand the formation and updating of these memory processes. Participants lifted, over multiple days, a set of black cubes with a normal size weight mapping and green cubes with an inverse size-weight mapping. Sensorimotor memory was assessed with lifting forces, and priors associated with the black and green cubes were assessed with the size-weight illusion (SWI). Interference was observed in terms of adaptation of the SWI, indicating that priors were not independently adjusted. Half of the participants rapidly learned to scale lift forces appropriately, whereas reduced learning was observed in the others, suggesting that individual differences may be affecting sensorimotor memory abilities. A follow-up experiment showed that lifting forces are not accurately scaled to objects when concurrently performing a visuomotor association task, suggesting that sensorimotor memory formation involves cognitive resources to instantiate the mapping between object identity and weight, potentially explaining the results of experiment 1 These results provide novel insight into the formation and updating of sensorimotor memories and provide support for the independent adjustment of sensorimotor memory and priors. PMID- 27385793 TI - Cognitive dysfunction in Duchenne muscular dystrophy: a possible role for neuromodulatory immune molecules. AB - Duchenne muscular dystrophy (DMD) is an X chromosome-linked disease characterized by progressive physical disability, immobility, and premature death in affected boys. Underlying the devastating symptoms of DMD is the loss of dystrophin, a structural protein that connects the extracellular matrix to the cell cytoskeleton and provides protection against contraction-induced damage in muscle cells, leading to chronic peripheral inflammation. However, dystrophin is also expressed in neurons within specific brain regions, including the hippocampus, a structure associated with learning and memory formation. Linked to this, a subset of boys with DMD exhibit nonprogressing cognitive dysfunction, with deficits in verbal, short-term, and working memory. Furthermore, in the genetically comparable dystrophin-deficient mdx mouse model of DMD, some, but not all, types of learning and memory are deficient, and specific deficits in synaptogenesis and channel clustering at synapses has been noted. Little consideration has been devoted to the cognitive deficits associated with DMD compared with the research conducted into the peripheral effects of dystrophin deficiency. Therefore, this review focuses on what is known about the role of full-length dystrophin (Dp427) in hippocampal neurons. The importance of dystrophin in learning and memory is assessed, and the potential importance that inflammatory mediators, which are chronically elevated in dystrophinopathies, may have on hippocampal function is also evaluated. PMID- 27385797 TI - Contribution of intravestibular sensory conflict to motion sickness and dizziness in migraine disorders. AB - Migraine is associated with enhanced motion sickness susceptibility and can cause episodic vertigo [vestibular migraine (VM)], but the mechanisms relating migraine to these vestibular symptoms remain uncertain. We tested the hypothesis that the central integration of rotational cues (from the semicircular canals) and gravitational cues (from the otolith organs) is abnormal in migraine patients. A postrotational tilt paradigm generated a conflict between canal cues (which indicate the head is rotating) and otolith cues (which indicate the head is tilted and stationary), and eye movements were measured to quantify two behaviors that are thought to minimize this conflict: suppression and reorientation of the central angular velocity signal, evidenced by attenuation ("dumping") of the vestibuloocular reflex and shifting of the rotational axis of the vestibuloocular reflex toward the earth vertical. We found that normal and migraine subjects, but not VM patients, displayed an inverse correlation between the extent of dumping and the size of the axis shift such that the net "conflict resolution" mediated through these two mechanisms approached an optimal value and that the residual sensory conflict in VM patients (but not migraine or normal subjects) correlated with motion sickness susceptibility. Our findings suggest that the brain normally controls the dynamic and spatial characteristics of central vestibular signals to minimize intravestibular sensory conflict and that this process is disrupted in VM, which may be responsible for the enhance motion intolerance and episodic vertigo that characterize this disorder. PMID- 27385796 TI - Glutamatergic drive facilitates synaptic inhibition of dorsal vagal motor neurons after experimentally induced diabetes in mice. AB - The role of central regulatory circuits in modulating diabetes-associated glucose dysregulation has only recently been under rigorous investigation. One brain region of interest is the dorsal motor nucleus of the vagus (DMV), which contains preganglionic parasympathetic motor neurons that regulate subdiaphragmatic visceral function. Previous research has demonstrated that glutamatergic and GABAergic neurotransmission are independently remodeled after chronic hyperglycemia/hypoinsulinemia. However, glutamatergic circuitry within the dorsal brain stem impinges on GABAergic regulation of the DMV. The present study investigated the role of glutamatergic neurotransmission in synaptic GABAergic control of DMV neurons after streptozotocin (STZ)-induced hyperglycemia/hypoinsulinemia by using electrophysiological recordings in vitro. The frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) was elevated in DMV neurons from STZ-treated mice. The effect was abolished in the presence of the ionotropic glutamate receptor blocker kynurenic acid or the sodium channel blocker tetrodotoxin, suggesting that after STZ-induced hyperglycemia/hypoinsulinemia, increased glutamatergic receptor activity occurs at a soma-dendritic location on local GABA neurons projecting to the DMV. Although sIPSCs in DMV neurons normally demonstrated considerable amplitude variability, this variability was significantly increased after STZ-induced hyperglycemia/hypoinsulinemia. The elevated amplitude variability was not related to changes in quantal release, but rather correlated with significantly elevated frequency of sIPSCs in these mice. Taken together, these findings suggest that GABAergic regulation of central vagal circuitry responsible for the regulation of energy homeostasis undergoes complex functional reorganization after several days of hyperglycemia/hypoinsulinemia, including both glutamate-dependent and independent forms of plasticity. PMID- 27385798 TI - The compensatory interaction between motor unit firing behavior and muscle force during fatigue. AB - Throughout the literature, different observations of motor unit firing behavior during muscle fatigue have been reported and explained with varieties of conjectures. The disagreement amongst previous studies has resulted, in part, from the limited number of available motor units and from the misleading practice of grouping motor unit data across different subjects, contractions, and force levels. To establish a more clear understanding of motor unit control during fatigue, we investigated the firing behavior of motor units from the vastus lateralis muscle of individual subjects during a fatigue protocol of repeated voluntary constant force isometric contractions. Surface electromyographic decomposition technology provided the firings of 1,890 motor unit firing trains. These data revealed that to sustain the contraction force as the muscle fatigued, the following occurred: 1) motor unit firing rates increased; 2) new motor units were recruited; and 3) motor unit recruitment thresholds decreased. Although the degree of these adaptations was subject specific, the behavior was consistent in all subjects. When we compared our empirical observations with those obtained from simulation, we found that the fatigue-induced changes in motor unit firing behavior can be explained by increasing excitation to the motoneuron pool that compensates for the fatigue-induced decrease in muscle force twitch reported in empirical studies. Yet, the fundamental motor unit control scheme remains invariant throughout the development of fatigue. These findings indicate that the central nervous system regulates motor unit firing behavior by adjusting the operating point of the excitation to the motoneuron pool to sustain the contraction force as the muscle fatigues. PMID- 27385799 TI - Membrane potential resonance frequency directly influences network frequency through electrical coupling. AB - Oscillatory networks often include neurons with membrane potential resonance, exhibiting a peak in the voltage amplitude as a function of current input at a nonzero (resonance) frequency (fres). Although fres has been correlated to the network frequency (fnet) in a variety of systems, a causal relationship between the two has not been established. We examine the hypothesis that combinations of biophysical parameters that shift fres, without changing other attributes of the impedance profile, also shift fnet in the same direction. We test this hypothesis, computationally and experimentally, in an electrically coupled network consisting of intrinsic oscillator (O) and resonator (R) neurons. We use a two-cell model of such a network to show that increasing fres of R directly increases fnet and that this effect becomes more prominent if the amplitude of resonance is increased. Notably, the effect of fres on fnet is independent of the parameters that define the oscillator or the combination of parameters in R that produce the shift in fres, as long as this combination produces the same impedance vs. frequency relationship. We use the dynamic clamp technique to experimentally verify the model predictions by connecting a model resonator to the pacemaker pyloric dilator neurons of the crab Cancer borealis pyloric network using electrical synapses and show that the pyloric network frequency can be shifted by changing fres in the resonator. Our results provide compelling evidence that fres and resonance amplitude strongly influence fnet, and therefore, modulators may target these attributes to modify rhythmic activity. PMID- 27385800 TI - Integration of autopatching with automated pipette and cell detection in vitro. AB - Patch clamp is the main technique for measuring electrical properties of individual cells. Since its discovery in 1976 by Neher and Sakmann, patch clamp has been instrumental in broadening our understanding of the fundamental properties of ion channels and synapses in neurons. The conventional patch-clamp method requires manual, precise positioning of a glass micropipette against the cell membrane of a visually identified target neuron. Subsequently, a tight "gigaseal" connection between the pipette and the cell membrane is established, and suction is applied to establish the whole cell patch configuration to perform electrophysiological recordings. This procedure is repeated manually for each individual cell, making it labor intensive and time consuming. In this article we describe the development of a new automatic patch-clamp system for brain slices, which integrates all steps of the patch-clamp process: image acquisition through a microscope, computer vision-based identification of a patch pipette and fluorescently labeled neurons, micromanipulator control, and automated patching. We validated our system in brain slices from wild-type and transgenic mice expressing channelrhodopsin 2 under the Thy1 promoter (line 18) or injected with a herpes simplex virus-expressing archaerhodopsin, ArchT. Our computer vision based algorithm makes the fluorescent cell detection and targeting user independent. Compared with manual patching, our system is superior in both success rate and average trial duration. It provides more reliable trial-to-trial control of the patching process and improves reproducibility of experiments. PMID- 27385801 TI - Spontaneous activity and functional connectivity in the developing cerebellorubral system. AB - The development of the cerebellar system depends in part on the emergence of functional connectivity in its input and output pathways. Characterization of spontaneous activity within these pathways provides insight into their functional status in early development. In the present study we recorded extracellular activity from the interpositus nucleus (IP) and its primary downstream target, the red nucleus (RN), in unanesthetized rats at postnatal days 8 (P8) and P12, a period of dramatic change in cerebellar circuitry. The two structures exhibited state-dependent activity patterns and age-related changes in rhythmicity and overall firing rate. Importantly, sensory feedback (i.e., reafference) from myoclonic twitches (spontaneous, self-generated movements that are produced exclusively during active sleep) drove neural activity in the IP and RN at both ages. Additionally, anatomic tracing confirmed the presence of cerebellorubral connections as early as P8. Finally, inactivation of the IP and adjacent nuclei using the GABAA receptor agonist muscimol caused a substantial decrease in neural activity in the contralateral RN at both ages, as well as the disappearance of rhythmicity; twitch-related activity in the RN, however, was preserved after IP inactivation, indicating that twitch-related reafference activates the two structures in parallel. Overall, the present findings point to the contributions of sleep-related spontaneous activity to the development of cerebellar networks. PMID- 27385802 TI - Optimal visuotactile integration for velocity discrimination of self-hand movements. AB - Illusory hand movements can be elicited by a textured disk or a visual pattern rotating under one's hand, while proprioceptive inputs convey immobility information (Blanchard C, Roll R, Roll JP, Kavounoudias A. PLoS One 8: e62475, 2013). Here, we investigated whether visuotactile integration can optimize velocity discrimination of illusory hand movements in line with Bayesian predictions. We induced illusory movements in 15 volunteers by visual and/or tactile stimulation delivered at six angular velocities. Participants had to compare hand illusion velocities with a 5 degrees /s hand reference movement in an alternative forced choice paradigm. Results showed that the discrimination threshold decreased in the visuotactile condition compared with unimodal (visual or tactile) conditions, reflecting better bimodal discrimination. The perceptual strength (gain) of the illusions also increased: the stimulation required to give rise to a 5 degrees /s illusory movement was slower in the visuotactile condition compared with each of the two unimodal conditions. The maximum likelihood estimation model satisfactorily predicted the improved discrimination threshold but not the increase in gain. When we added a zero-centered prior, reflecting immobility information, the Bayesian model did actually predict the gain increase but systematically overestimated it. Interestingly, the predicted gains better fit the visuotactile performances when a proprioceptive noise was generated by covibrating antagonist wrist muscles. These findings show that kinesthetic information of visual and tactile origins is optimally integrated to improve velocity discrimination of self-hand movements. However, a Bayesian model alone could not fully describe the illusory phenomenon pointing to the crucial importance of the omnipresent muscle proprioceptive cues with respect to other sensory cues for kinesthesia. PMID- 27385804 TI - Choosing Dialysis Modality-Patient Choice or Physician Bias? PMID- 27385805 TI - Do Dialysis Decision Aids Improve Treatment Decision-Making? PMID- 27385803 TI - Selenium and Prostate Cancer: Analysis of Individual Participant Data From Fifteen Prospective Studies. AB - BACKGROUND: Some observational studies suggest that a higher selenium status is associated with a lower risk of prostate cancer but have been generally too small to provide precise estimates of associations, particularly by disease stage and grade. METHODS: Collaborating investigators from 15 prospective studies provided individual-participant records (from predominantly men of white European ancestry) on blood or toenail selenium concentrations and prostate cancer risk. Odds ratios of prostate cancer by selenium concentration were estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided. RESULTS: Blood selenium was not associated with the risk of total prostate cancer (multivariable-adjusted odds ratio [OR] per 80 percentile increase = 1.01, 95% confidence interval [CI] = 0.83 to 1.23, based on 4527 case patients and 6021 control subjects). However, there was heterogeneity by disease aggressiveness (ie, advanced stage and/or prostate cancer death, Pheterogeneity = .01), with high blood selenium associated with a lower risk of aggressive disease (OR = 0.43, 95% CI = 0.21 to 0.87) but not with nonaggressive disease. Nail selenium was inversely associated with total prostate cancer (OR = 0.29, 95% CI = 0.22 to 0.40, Ptrend < .001, based on 1970 case patients and 2086 control subjects), including both nonaggressive (OR = 0.33, 95% CI = 0.22 to 0.50) and aggressive disease (OR = 0.18, 95% CI = 0.11 to 0.31, Pheterogeneity = .08). CONCLUSIONS: Nail, but not blood, selenium concentration is inversely associated with risk of total prostate cancer, possibly because nails are a more reliable marker of long-term selenium exposure. Both blood and nail selenium concentrations are associated with a reduced risk of aggressive disease, which warrants further investigation. PMID- 27385806 TI - Telemedicine and Remote Monitoring: Supporting the Patient on Peritoneal Dialysis. PMID- 27385807 TI - Stability of Cefepime in pH-Neutral Peritoneal Dialysis Solutions Packaged in Dual-Compartment Bags. AB - Intraperitoneal cefepime is used for the treatment of peritoneal dialysis (PD) associated peritonitis caused by gram-negative bacteria. The current study investigated the stability of cefepime in a pH-neutral PD solution. A reconstituted solution of cefepime was injected into a total of 9 PD bags and stored at 4 degrees C, 25 degrees C or 37 degrees C for various time points. Cefepime retained more than 90% of its initial concentration for 168, 96, and 12 hours at 4 degrees C, 25 degrees C and 37 degrees C, respectively. No apparent physical precipitation or pH change was observed during the study. This study provides crucial information to healthcare professionals on the physical and chemical stability of cefepime in the pH-neutral solution to help them in preparing such admixtures in advance where required. PMID- 27385808 TI - The Enigmatic Fallopian Tube: A More Common Cause of Catheter Malfunction than Previously Recognized. AB - Successful performance of peritoneal dialysis (PD) depends on a properly functioning PD catheter. Catheter malfunction remains a significant cause of technique failure, especially early in the course of therapy. Common causes of catheter malfunction include catheter displacement, omental or bowel wrapping, and fibrin clots. Less commonly, various intraperitoneal structures have been reported to lead to obstruction, including appendices epiploicae of sigmoid colon and the fallopian tube. Peritoneal dialysis catheter blockage due to fimbriae of the fallopian tube is being recognized as an important cause of catheter malfunction in females due to the increasing availability of diagnostic laparoscopy. We report 5 episodes of catheter malfunction in 4 patients on PD from a single center as a result of obstruction by the fallopian tube. PMID- 27385809 TI - Diagnosing Tuberculous Peritonitis Early in Patients on Peritoneal Dialysis: Use of Xpert MTB/RIF Assay. AB - Diagnosing tuberculous peritonitis can be challenging, with mycobacterial culture potentially taking weeks for a positive result. This report describes 2 cases where a prompt diagnosis of tuberculous peritonitis was made employing the Xpert MTB/RIF assay (Cepheid Inc., Sunnyvale, CA, USA). PMID- 27385810 TI - A Qualitative Assessment of Mismatch Between Dialysis Modality Selection and Initiation. AB - At our institution, we have noted that end-stage renal disease patients choosing a home dialysis modality after education often initiate renal replacement therapy with in-center hemodialysis (HD) instead. We interviewed 24 such patients (23 choosing peritoneal dialysis [PD], one choosing home HD) to determine reasons for this mismatch. The most common reasons cited for not starting home dialysis were: lack of confidence/concerns about complications, lack of space or home-related issues, a feeling of insufficient education, and perceived medical or social contraindications. We propose several potential strategies to help patients start with their preferred modality. PMID- 27385811 TI - Randomized n-of-1 Trials: Quality Improvement, Research, or Both? AB - The regulatory demarcations between clinical research and quality improvement (QI) are ambiguous and controversial. Some projects that were undertaken as a form of QI were deemed by regulatory agencies to be research and thus to require institutional review board approval. In the era of personalized medicine, some physicians may ask some patients to participate in n-of-1 trials in an effort to personalize and optimize each patient's medical treatment. Should such activities be considered research, QI, or just excellent personalized medicine? Experts in research, research regulation, and bioethics analyze these issues. PMID- 27385812 TI - Practice Patterns in Medicaid and Non-Medicaid Asthma Admissions. AB - BACKGROUND AND OBJECTIVES: With American children experiencing increased Medicaid coverage, it has become especially important to determine if practice patterns differ between Medicaid and non-Medicaid patients. Auditing such potential differences must carefully compare like patients to avoid falsely identifying suspicious practice patterns. We asked if we could observe differences in practice patterns between Medicaid and non-Medicaid patients admitted for asthma inside major children's hospitals. METHODS: A matched cohort design, studying 17 739 matched pairs of children (Medicaid to non-Medicaid) admitted for asthma in the same hospital between April 1, 2011 and March 31, 2014 in 40 Children's Hospital Association hospitals contributing data to the Pediatric Hospital Information System database. Patients were matched on age, sex, asthma severity, and other patient characteristics. RESULTS: Medicaid patient median cost was $4263 versus $4160 for non-Medicaid patients (P < .001). Additionally, the median cost difference (Medicaid minus non-Medicaid) between individual pairs was only $84 (95% confidence interval: 44 to 124), and the mean cost difference was only $49 (95% confidence interval: -72 to 170). The 90th percentile costs were also similar between groups ($10 710 vs $10 948; P < .07). Length of stay (LOS) was also very similar; both groups had a median stay of 1 day, with a similar percentage of patients exceeding the 90th percentile of individual hospital LOS (7.1% vs 6.7%; P = .14). ICU use was also similar (10.1% vs 10.6%; P = .12). CONCLUSIONS: For closely matched patients within the same hospital, Medicaid status did not importantly influence costs, LOS, or ICU use. PMID- 27385813 TI - CORRECTION. PMID- 27385815 TI - Divide and Conquer: Introducing a Novel Player in Cell Plate Formation. PMID- 27385814 TI - In Planta Single-Molecule Pull-Down Reveals Tetrameric Stoichiometry of HD ZIPIII:LITTLE ZIPPER Complexes. AB - Deciphering complex biological processes markedly benefits from approaches that directly assess the underlying biomolecular interactions. Most commonly used approaches to monitor protein-protein interactions typically provide nonquantitative readouts that lack statistical power and do not yield information on the heterogeneity or stoichiometry of protein complexes. Single-molecule pull down (SiMPull) uses single-molecule fluorescence detection to mitigate these disadvantages and can quantitatively interrogate interactions between proteins and other compounds, such as nucleic acids, small molecule ligands, and lipids. Here, we establish SiMPull in plants using the HOMEODOMAIN LEUCINE ZIPPER III (HD ZIPIII) and LITTLE ZIPPER (ZPR) interaction as proof-of-principle. Colocalization analysis of fluorophore-tagged HD-ZIPIII and ZPR proteins provides strong statistical evidence of complex formation. In addition, we use SiMPull to directly quantify YFP and mCherry maturation probabilities, showing these differ substantially from values obtained in mammalian systems. Leveraging these probabilities, in conjunction with fluorophore photobleaching assays on over 2000 individual complexes, we determined HD-ZIPIII:ZPR stoichiometry. Intriguingly, these complexes appear as heterotetramers, comprising two HD-ZIPIII and two ZPR molecules, rather than heterodimers as described in the current model. This surprising result raises new questions about the regulation of these key developmental factors and is illustrative of the unique contribution SiMPull is poised to make to in planta protein interaction studies. PMID- 27385816 TI - CLAUSA Is a MYB Transcription Factor That Promotes Leaf Differentiation by Attenuating Cytokinin Signaling. AB - Leaf morphogenesis and differentiation are highly flexible processes, resulting in a large diversity of leaf forms. The development of compound leaves involves an extended morphogenesis stage compared with that of simple leaves, and the tomato (Solanum lycopersicum) mutant clausa (clau) exposes a potential for extended morphogenesis in tomato leaves. Here, we report that the CLAU gene encodes a MYB transcription factor that has evolved a unique role in compound leaf species to promote an exit from the morphogenetic phase of tomato leaf development. We show that CLAU attenuates cytokinin signaling, and that clau plants have increased cytokinin sensitivity. The results suggest that flexible leaf patterning involves a coordinated interplay between transcription factors and hormones. PMID- 27385817 TI - Local Auxin Biosynthesis Mediated by a YUCCA Flavin Monooxygenase Regulates Haustorium Development in the Parasitic Plant Phtheirospermum japonicum. AB - Parasitic plants in the Orobanchaceae cause serious agricultural problems worldwide. Parasitic plants develop a multicellular infectious organ called a haustorium after recognition of host-released signals. To understand the molecular events associated with host signal perception and haustorium development, we identified differentially regulated genes expressed during early haustorium development in the facultative parasite Phtheirospermum japonicum using a de novo assembled transcriptome and a customized microarray. Among the genes that were upregulated during early haustorium development, we identified YUC3, which encodes a functional YUCCA (YUC) flavin monooxygenase involved in auxin biosynthesis. YUC3 was specifically expressed in the epidermal cells around the host contact site at an early time point in haustorium formation. The spatio temporal expression patterns of YUC3 coincided with those of the auxin response marker DR5, suggesting generation of auxin response maxima at the haustorium apex. Roots transformed with YUC3 knockdown constructs formed haustoria less frequently than nontransgenic roots. Moreover, ectopic expression of YUC3 at the root epidermal cells induced the formation of haustorium-like structures in transgenic P. japonicum roots. Our results suggest that expression of the auxin biosynthesis gene YUC3 at the epidermal cells near the contact site plays a pivotal role in haustorium formation in the root parasitic plant P. japonicum. PMID- 27385818 TI - The PHD Finger Protein MMD1/DUET Ensures the Progression of Male Meiotic Chromosome Condensation and Directly Regulates the Expression of the Condensin Gene CAP-D3. AB - Chromosome condensation, a process mediated by the condensin complex, is essential for proper chromosome segregation during cell division. Unlike rapid mitotic chromosome condensation, meiotic chromosome condensation occurs over a relatively long prophase I and is unusually complex due to the coordination with chromosome axis formation and homolog interaction. The molecular mechanisms that regulate meiotic chromosome condensation progression from prophase I to metaphase I are unclear. Here, we show that the Arabidopsis thaliana meiotic PHD-finger protein MMD1/DUET is required for progressive compaction of prophase I chromosomes to metaphase I bivalents. The MMD1 PHD domain is required for its function in chromosome condensation and binds to methylated histone tails. Transcriptome analysis and qRT-PCR showed that several condensin genes exhibit significantly reduced expression in mmd1 meiocytes. Furthermore, MMD1 specifically binds to the promoter region of the condensin subunit gene CAP-D3 to enhance its expression. Moreover, cap-d3 mutants exhibit similar chromosome condensation defects, revealing an MMD1-dependent mechanism for regulating meiotic chromosome condensation, which functions in part by promoting condensin gene expression. Together, these discoveries provide strong evidence that the histone reader MMD1/DUET defines an important step for regulating the progression of meiotic prophase I chromosome condensation. PMID- 27385820 TI - Recent Progress in Understanding the Role of Reactive Oxygen Species in Plant Cell Signaling. PMID- 27385822 TI - Plant Physiology 90th Anniversary. PMID- 27385819 TI - Salt Stress Reveals a New Role for ARGONAUTE1 in miRNA Biogenesis at the Transcriptional and Posttranscriptional Levels. AB - Plants as sessile organisms have developed prompt response mechanisms to react to rapid environmental changes. In addition to the transcriptional regulation of gene expression, microRNAs (miRNAs) are key posttranscriptional regulators of the plant stress response. We show here that the expression levels of many miRNAs were regulated under salt stress conditions. This regulation occurred at the transcriptional and posttranscriptional levels. During salinity stress, the levels of miRNA161 and miRNA173 increased, while the expression of pri-miRNA161 and pri-miRNA173 was down-regulated. Under salt stress conditions, miRNA161 and miRNA173 were stabilized in the cytoplasm, and the expressions of MIR161 and MIR173 were negatively regulated in the nucleus. ARGONAUTE1 (AGO1) participated in both processes. We demonstrated that AGO1 cotranscriptionally controlled the expression of MIR161 and MIR173 in the nucleus. Our results suggests that AGO1 interacts with chromatin at MIR161 and MIR173 loci and causes the disassembly of the transcriptional complex, releasing short and unpolyadenylated transcripts. PMID- 27385821 TI - Aquaporins Link ROS Signaling to Plant Immunity. PMID- 27385823 TI - Cellular heterogeneity mediates inherent sensitivity-specificity tradeoff in cancer targeting by synthetic circuits. AB - Synthetic gene circuits are emerging as a versatile means to target cancer with enhanced specificity by combinatorial integration of multiple expression markers. Such circuits must also be tuned to be highly sensitive because escape of even a few cells might be detrimental. However, the error rates of decision-making circuits in light of cellular variability in gene expression have so far remained unexplored. Here, we measure the single-cell response function of a tunable logic AND gate acting on two promoters in heterogeneous cell populations. Our analysis reveals an inherent tradeoff between specificity and sensitivity that is controlled by the AND gate amplification gain and activation threshold. We implement a tumor-mimicking cell-culture model of cancer cells emerging in a background of normal ones, and show that molecular parameters of the synthetic circuits control specificity and sensitivity in a killing assay. This suggests that, beyond the inherent tradeoff, synthetic circuits operating in a heterogeneous environment could be optimized to efficiently target malignant state with minimal loss of specificity. PMID- 27385824 TI - Higher thermoelectric performance of Zintl phases (Eu0.5Yb0.5)1-xCaxMg2Bi2 by band engineering and strain fluctuation. AB - Complex Zintl phases, especially antimony (Sb)-based YbZn0.4Cd1.6Sb2 with figure of-merit (ZT) of ~1.2 at 700 K, are good candidates as thermoelectric materials because of their intrinsic "electron-crystal, phonon-glass" nature. Here, we report the rarely studied p-type bismuth (Bi)-based Zintl phases (Ca,Yb,Eu)Mg2Bi2 with a record thermoelectric performance. Phase-pure EuMg2Bi2 is successfully prepared with suppressed bipolar effect to reach ZT ~ 1. Further partial substitution of Eu by Ca and Yb enhanced ZT to ~1.3 for Eu0.2Yb0.2Ca0.6Mg2Bi2 at 873 K. Density-functional theory (DFT) simulation indicates the alloying has no effect on the valence band, but does affect the conduction band. Such band engineering results in good p-type thermoelectric properties with high carrier mobility. Using transmission electron microscopy, various types of strains are observed and are believed to be due to atomic mass and size fluctuations. Point defects, strain, dislocations, and nanostructures jointly contribute to phonon scattering, confirmed by the semiclassical theoretical calculations based on a modified Debye-Callaway model of lattice thermal conductivity. This work indicates Bi-based (Ca,Yb,Eu)Mg2Bi2 is better than the Sb-based Zintl phases. PMID- 27385825 TI - CCR7 expression alters memory CD8 T-cell homeostasis by regulating occupancy in IL-7- and IL-15-dependent niches. AB - C-C receptor 7 (CCR7) is important to allow T cells and dendritic cells to migrate toward CCL19- and CCL21-producing cells in the T-cell zone of the spleen and lymph nodes. The role of this chemokine receptor in regulating the homeostasis of effector and memory T cells during acute viral infection is poorly defined, however. In this study, we show that CCR7 expression alters memory CD8 T cell homeostasis following lymphocytic choriomeningitis virus infection. Greater numbers of CCR7-deficient memory T cells were formed and maintained compared with CCR7-sufficient memory T cells, especially in the lung and bone marrow. The CCR7 deficient memory T cells also displayed enhanced rates of homeostatic turnover, which may stem from increased exposure to IL-15 as a consequence of reduced exposure to IL-7, because removal of IL-15, but not of IL-7, normalized the numbers of CCR7-sufficient and CCR7-deficient memory CD8 T cells. This result suggests that IL-15 is the predominant cytokine supporting augmentation of the CCR7(-/-) memory CD8 T-cell pool. Taken together, these data suggest that CCR7 biases memory CD8 T cells toward IL-7-dependent niches over IL-15-dependent niches, which provides insight into the homeostatic regulation of different memory T-cell subsets. PMID- 27385826 TI - Numerous proteins with unique characteristics are degraded by the 26S proteasome following monoubiquitination. AB - The "canonical" proteasomal degradation signal is a substrate-anchored polyubiquitin chain. However, a handful of proteins were shown to be targeted following monoubiquitination. In this study, we established-in both human and yeast cells-a systematic approach for the identification of monoubiquitination dependent proteasomal substrates. The cellular wild-type polymerizable ubiquitin was replaced with ubiquitin that cannot form chains. Using proteomic analysis, we screened for substrates that are nevertheless degraded under these conditions compared with those that are stabilized, and therefore require polyubiquitination for their degradation. For randomly sampled representative substrates, we confirmed that their cellular stability is in agreement with our screening prediction. Importantly, the two groups display unique features: monoubiquitinated substrates are smaller than the polyubiquitinated ones, are enriched in specific pathways, and, in humans, are structurally less disordered. We suggest that monoubiquitination-dependent degradation is more widespread than assumed previously, and plays key roles in various cellular processes. PMID- 27385827 TI - Source-sink plasmid transfer dynamics maintain gene mobility in soil bacterial communities. AB - Horizontal gene transfer is a fundamental process in bacterial evolution that can accelerate adaptation via the sharing of genes between lineages. Conjugative plasmids are the principal genetic elements mediating the horizontal transfer of genes, both within and between bacterial species. In some species, plasmids are unstable and likely to be lost through purifying selection, but when alternative hosts are available, interspecific plasmid transfer could counteract this and maintain access to plasmid-borne genes. To investigate the evolutionary importance of alternative hosts to plasmid population dynamics in an ecologically relevant environment, we established simple soil microcosm communities comprising two species of common soil bacteria, Pseudomonas fluorescens and Pseudomonas putida, and a mercury resistance (Hg(R)) plasmid, pQBR57, both with and without positive selection [i.e., addition of Hg(II)]. In single-species populations, plasmid stability varied between species: although pQBR57 survived both with and without positive selection in P. fluorescens, it was lost or replaced by nontransferable Hg(R) captured to the chromosome in P. putida A simple mathematical model suggests these differences were likely due to pQBR57's lower intraspecific conjugation rate in P. putida By contrast, in two-species communities, both models and experiments show that interspecific conjugation from P. fluorescens allowed pQBR57 to persist in P. putida via source-sink transfer dynamics. Moreover, the replacement of pQBR57 by nontransferable chromosomal Hg(R) in P. putida was slowed in coculture. Interspecific transfer allows plasmid survival in host species unable to sustain the plasmid in monoculture, promoting community-wide access to the plasmid-borne accessory gene pool and thus potentiating future evolvability. PMID- 27385828 TI - Structure and function of the yeast listerin (Ltn1) conserved N-terminal domain in binding to stalled 60S ribosomal subunits. AB - The Ltn1 E3 ligase (listerin in mammals) has emerged as a paradigm for understanding ribosome-associated ubiquitylation. Ltn1 binds to 60S ribosomal subunits to ubiquitylate nascent polypeptides that become stalled during synthesis; among Ltn1's substrates are aberrant products of mRNA lacking stop codons [nonstop translation products (NSPs)]. Here, we report the reconstitution of NSP ubiquitylation in Neurospora crassa cell extracts. Upon translation in vitro, ribosome-stalled NSPs were ubiquitylated in an Ltn1-dependent manner, while still ribosome-associated. Furthermore, we provide biochemical evidence that the conserved N-terminal domain (NTD) plays a significant role in the binding of Ltn1 to 60S ribosomal subunits and that NTD mutations causing defective 60S binding also lead to defective NSP ubiquitylation, without affecting Ltn1's intrinsic E3 ligase activity. Finally, we report the crystal structure of the Ltn1 NTD at 2.4-A resolution. The structure, combined with additional mutational studies, provides insight to NTD's role in binding stalled 60S subunits. Our findings show that Neurospora extracts can be used as a tool to dissect mechanisms underlying ribosome-associated protein quality control and are consistent with a model in which Ltn1 uses 60S subunits as adapters, at least in part via its NTD, to target stalled NSPs for ubiquitylation. PMID- 27385829 TI - Dynamics and architecture of the NRBF2-containing phosphatidylinositol 3-kinase complex I of autophagy. AB - The class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) is central to autophagy initiation. We previously reported the V-shaped architecture of the four-subunit version of PI3KC3-C1 consisting of VPS (vacuolar protein sorting) 34, VPS15, BECN1 (Beclin 1), and ATG (autophagy-related) 14. Here we show that a putative fifth subunit, nuclear receptor binding factor 2 (NRBF2), is a tightly bound component of the complex that profoundly affects its activity and architecture. NRBF2 enhances the lipid kinase activity of the catalytic subunit, VPS34, by roughly 10-fold. We used hydrogen-deuterium exchange coupled to mass spectrometry and negative-stain electron microscopy to map NRBF2 to the base of the V-shaped complex. NRBF2 interacts primarily with the N termini of ATG14 and BECN1. We show that NRBF2 is a homodimer and drives the dimerization of the larger PI3KC3-C1 complex, with implications for the higher-order organization of the preautophagosomal structure. PMID- 27385831 TI - Rationalizing spatial exploration patterns of wild animals and humans through a temporal discounting framework. AB - Understanding the exploration patterns of foragers in the wild provides fundamental insight into animal behavior. Recent experimental evidence has demonstrated that path lengths (distances between consecutive turns) taken by foragers are well fitted by a power law distribution. Numerous theoretical contributions have posited that "Levy random walks"-which can produce power law path length distributions-are optimal for memoryless agents searching a sparse reward landscape. It is unclear, however, whether such a strategy is efficient for cognitively complex agents, from wild animals to humans. Here, we developed a model to explain the emergence of apparent power law path length distributions in animals that can learn about their environments. In our model, the agent's goal during search is to build an internal model of the distribution of rewards in space that takes into account the cost of time to reach distant locations (i.e., temporally discounting rewards). For an agent with such a goal, we find that an optimal model of exploration in fact produces hyperbolic path lengths, which are well approximated by power laws. We then provide support for our model by showing that humans in a laboratory spatial exploration task search space systematically and modify their search patterns under a cost of time. In addition, we find that path length distributions in a large dataset obtained from free-ranging marine vertebrates are well described by our hyperbolic model. Thus, we provide a general theoretical framework for understanding spatial exploration patterns of cognitively complex foragers. PMID- 27385830 TI - Deletion of a dehydratase important for intracellular growth and cording renders rough Mycobacterium abscessus avirulent. AB - Mycobacterium abscessus (Mabs) is a rapidly growing Mycobacterium and an emerging pathogen in humans. Transitioning from a smooth (S) high-glycopeptidolipid (GPL) producer to a rough (R) low-GPL producer is associated with increased virulence in zebrafish, which involves the formation of massive serpentine cords, abscesses, and rapid larval death. Generating a cord-deficient Mabs mutant would allow us to address the contribution of cording in the physiopathological signs of the R variant. Herein, a deletion mutant of MAB_4780, encoding a dehydratase, distinct from the beta-hydroxyacyl-ACP dehydratase HadABC complex, was constructed in the R morphotype. This mutant exhibited an alteration of the mycolic acid composition and a pronounced defect in cording. This correlated with an extremely attenuated phenotype not only in wild-type but also in immunocompromised zebrafish embryos lacking either macrophages or neutrophils. The abolition of granuloma formation in embryos infected with the dehydratase mutant was associated with a failure to replicate in macrophages, presumably due to limited inhibition of the phagolysosomal fusion. Overall, these results indicate that MAB_4780 is required for Mabs to successfully establish acute and lethal infections. Therefore, targeting MAB_4780 may represent an attractive antivirulence strategy to control Mabs infections, refractory to most standard chemotherapeutic interventions. The combination of a dehydratase assay with a high-resolution crystal structure of MAB_4780 opens the way to identify such specific inhibitors. PMID- 27385832 TI - An interdisciplinary clinic in rural Tanzania - observations on chiropractic care in a developing nation. AB - It appears that a great many chiropractors and chiropractic institutions are involved in health care initiatives in developing countries. Developing nations present extraordinary opportunities to do good, but also carry risks, for practitioners and organizations, which may not be obvious prior to actual local engagement. This paper describes the guiding principles under which one international collaboration has evolved in rural Tanzania, a so-called 'low resource' setting where the majority of families subsist in extreme poverty. Several challenges to effective care are also identified. PMID- 27385833 TI - Effect of two consecutive spinal manipulations in a single session on myofascial pain pressure sensitivity: a randomized controlled trial. AB - OBJECTIVE: To investigate the summative effect of two consecutive spinal manipulative therapy (SMT) interventions within the same session on the pain pressure sensitivity of neurosegmentally linked myofascial tissues. METHODS: 26 participants were recruited and assessed for the presence of a clinically identifiable myofascial trigger point in the right infraspinatus muscle. Participants were randomly assigned to test or control group. Test group received two consecutive real cervical SMT interventions to C5-C6 segment while controls received one real SMT followed by one validated sham SMT intervention to C5-C6 segment. Participants received the two consecutive SMT interventions 30 minutes apart. Pain pressure threshold (PPT) readings were recorded at pre-SMT1 and 5, 10, 15, 20 and 25 minutes post-SMT1 and post-SMT2. PPT readings were normalized to pre-SMT1 values and averaged. RESULTS: Repeated measures ANOVA demonstrated a significant main effect of SMT intervention [F(1,24)=8.60, p<0.05] but not group [F(1.24)=0.01] (p=0.91). Post-hoc comparisons demonstrated a statistically significant (p<0.05) increase in SMT2 versus SMT1 (18%) in the test group but not in controls (4%) (p=0.82). CONCLUSIONS: Two consecutive SMT interventions evoke significant decreases in mechanical pressure sensitivity (increased PPT) within neurosegmentally linked myofascial tissues. The antinociceptive effects of SMT may be summative and governed by a dose-response relationship in myofascial tissues. PMID- 27385834 TI - The reliability of lumbar motion palpation using continuous analysis and confidence ratings: choosing a relevant index of agreement. AB - INTRODUCTION: Most studies show motion palpation unreliable. This study's primary objective was assessing its reliability using a continuous measure methods, most fixated level paradigm, stratified by examiners' confidence; and the secondary objective was comparing various indices of examiner agreement. METHODS: Thirty four minimally symptomatic participants were palpated in side posture by two experienced examiners. Interexaminer differences in identifying the most-fixated level and degree of examiner confidence were recorded. Indices of agreement were: Intraclass correlation coefficient, Mean and Median Examiner Absolute Examiner Differences, Root-Mean-Square Error and Bland-Altman Limits of Agreement. RESULTS: Three of four reliability indices (excluding intraclass correlation) suggested on average examiners agreed on the most fixated motion segment, and agreement increased with confidence. Statistical measures of data dispersion were low. The analyses of subgroups were "fragile" due to small sample size. DISCUSSION: Although subject homogeneity lowered ICC levels, the other reliability measures were not similarly impacted. Continuous measures statistical analysis demonstrates examiner agreement in situations where discrete analysis with kappa may not. CONCLUSION: Continuous analysis for the lumbar most-fixated level is reliable. Future studies will need a larger sample size to properly analyze subgroups based on examiner confidence. PMID- 27385835 TI - The use of spinal manipulation to treat an acute on field athletic injury: a case report. AB - This case describes the utilization of spinal manipulative therapy for an acute athletic injury during a Taekwondo competition. During the tournament, an athlete had a sudden, non-traumatic, ballistic movement of the cervical spine. This resulted in the patient having a locked cervical spine with limited active motion in all directions. The attending chiropractor assessed the athlete, and deemed manipulation was appropriate. After the manipulation, the athlete's range of motion was returned and was able to finish the match. Spinal manipulation has multiple positive outcomes for an athlete with an acute injury including the increase of range of motion, decrease in pain and the relaxation of hypertonic muscles. However, there should be some caution when utilizing manipulation during an event. In the article the authors propose four criteria that should be met before utilizing manipulation for an acute, in competition, athletic injury. These include the lack of red flags, limited time for the intervention, preexisting doctor-patient relationship and the athlete has experience receiving spinal manipulation. Clinicians should be aware that manipulation may be an effective tool to treat an acute in competition athletic injury. The criteria set out in the article may help a practitioner decide if manipulation is a good option for them. PMID- 27385836 TI - Conservative management of posterior ankle impingement: a case report. AB - OBJECTIVE: To describe the pain and functional improvements of a patient with posterior ankle impingement following a treatment plan incorporating soft tissue therapy, chiropractic adjustment and a progressive rehabilitation program. CLINICAL FEATURES: A 37-year- old male presented with posterolateral ankle pain exacerbated by plantar flexion two weeks after sustaining an inversion ankle sprain. Oedema was present and the patient was describing a sensation of instability while walking. The initial diagnosis of lateral ankle sprain was found to be complicated by a posterior ankle impingement caused by a tenosynovitis of the flexor hallucis longus sheath suspected during the physical examination and confirmed by MRI. INTERVENTION AND OUTCOME: The patient was treated over a 14-week period. Soft tissue therapy, a rehabilitation program and cortisone injection were used to treat this condition. A precise description of the rehabilitation program that contains open kinetic chain, closed kinetic chain, proprioception, and conditioning exercises prescribed to the patient is given. After the treatment plan, the patient returned to play pain free and had no daily living restrictions. SUMMARY: A protocol including rest, soft tissue therapy, open and closed kinetic chain exercises, sport-specific exercises and cortisone injection appeared to facilitate complete recovery of this patient's posterior ankle impingement. PMID- 27385837 TI - Identification and management of chronic shoulder pain in the presence of an MRA confirmed humeral avulsion of the inferior glenohumeral ligament (HAGL) lesion. AB - OBJECTIVE: To present the assessment and conservative management of chronic shoulder pain in the presence of a humeral avulsion of the inferior glenohumeral ligament (HAGL) lesion in an active individual. CLINICAL FEATURES: A 47 year-old female office-worker with constant, deep, right shoulder pain with occasional clicking and catching claimed to have "tore something" in her right shoulder five years ago while performing reverse bicep curls. A physical exam led to differential diagnoses of a Superior Labrum Anterior to Posterior (SLAP) lesion, Bankart lesion, and bicipital tendinopathy. A Magnetic Resonance Arthrogram revealed a HAGL lesion. INTERVENTION AND OUTCOME: A conservative chiropractic treatment plan in addition to physical therapy was initiated. The patient reported 75% improvement in symptoms after 4 treatments over a four-week duration. SUMMARY: This case demonstrates the successful implementation of a conservative plan of management suggesting that the treatment provided to this patient should be considered and attempted prior to arthroscopic surgery. PMID- 27385838 TI - High incidence of persistence of sacral and coccygeal intervertebral discs in South Indians - a cadaveric study. AB - The sacrum, by virtue of its anatomic location plays a key role in providing stability and strength to the pelvis. Presence of intervertebral discs in sacrum and coccyx is rare. Knowledge of its variations is of utmost importance to surgeons and radiologists. The current study focused on the presence of intervertebral discs between the sacral and coccygeal vertebrae in south Indian cadaveric pelvises. We observed 56 adult pelvises of which, 34 (61%) pelvises showed the presence of intervertebral discs between the sacral vertebrae and between the coccygeal vertebrae, while 22 (39%) pelvises did not have the intervertebral discs either in the sacrum or the coccyx. We also found that most of the specimens had discs between S1 and S2 vertebrae (39%), followed by, between S4 and S5 (18%), between S2-S3 (14%) and least being between S3-S4 (13%). In the coccyx it was found that 7% of pelvises had disc between Co1-Co2, 4% of them had between Co2-Co3 and 4% had between Co3-Co4. Knowledge regarding such anatomic variations in the sacro-coccygeal region is important to note because they require alterations in various instrumentation procedures involving the sacrum. PMID- 27385839 TI - Subluxation and semantics: a corpus linguistics study. AB - INTRODUCTION: The purpose of this study was to analyze the curriculum of one chiropractic college in order to discover if there were any implicit consensus definitions of the term subluxation. METHODS: Using the software WordSmith Tools, the corpus of an undergraduate chiropractic curriculum was analyzed by reviewing collocated terms and through discourse analysis of text blocks containing words based on the root 'sublux.' RESULTS: It was possible to identify 3 distinct concepts which were each referred to as 'subluxation:' i) an acute or instantaneous injurious event; ii) a clinical syndrome which manifested post injury; iii) a physical lesion, i.e. an anatomical or physiological derangement which in most instances acted as a pain generator. CONCLUSIONS: In fact, coherent implicit definitions of subluxation exist and may enjoy broad but subconscious acceptance. However, confusion likely arises from failure to distinguish which concept an author or speaker is referring to when they employ the term subluxation. PMID- 27385840 TI - Classification of psychotropic drugs: Problems, solutions, and more problems. PMID- 27385841 TI - Mental health legislation: A journey back to "madhouses era?". PMID- 27385842 TI - Undergraduate psychiatry training in India; past, present, and future looking for solutions within constraints!! PMID- 27385843 TI - The rights of persons with Disability Bill, 2014: How "enabling" is it for persons with mental illness? AB - India ratified the United Nations Convention on the Rights of Person with Disabilities (UNCRPD) in 2007. This is a welcome step towards realizing the rights of the persons with disability. The UNCRPD proclaims that disability results from interaction of impairments with attitudinal and environmental barriers which hinders full and active participation in society on an equal basis with others. Further, the convention also mandates the signatory governments to change their local laws, to identify and eliminate obstacles and barriers and to comply with the terms of the UNCRPD in order to protect the rights of the person with disabilities, hence the amendments of the national laws. Hence, the Government of India drafted two important bill the Right of Persons with Disabilities Bill, 2014 (RPWD Bill, 2014) and Mental Health Care Bill, 2013 (MHC Bill, 2013). There is no doubt that persons with mental illness are stigmatized and discriminated across the civil societies, which hinders full and active participation in society. This situation becomes worse with regard to providing mental health care, rehabilitation and social welfare measures to persons with mental illness. There is an urgent need to address this issue of attitudinal barrier so that the rights of persons with mental illness is upheld. Hence, this article discusses shortcomings in the Right of Persons with Disabilities Bill, 2014 (RPWD Bill, 2014) from the perspective of persons with mental illness. Further, the article highlights the need to synchronize both the RPWD Bill, 2014 and Mental Health Care Bill, 2013 to provide justice for persons with mental illness. PMID- 27385844 TI - A study on phenomenology of Dhat syndrome in men in a general medical setting. AB - BACKGROUND: "Dhat syndrome" is believed to be a culture-bound syndrome of the Indian subcontinent. Although many studies have been performed, many have methodological limitations and there is a lack of agreement in many areas. AIMS: The aim is to study the phenomenology of "Dhat syndrome" in men and to explore the possibility of subtypes within this entity. SETTINGS AND DESIGN: It is a cross-sectional descriptive study conducted at a sex and marriage counseling clinic of a tertiary care teaching hospital in Northern India. MATERIALS AND METHODS: An operational definition and assessment instrument for "Dhat syndrome" was developed after taking all concerned stakeholders into account and review of literature. It was applied on 100 patients along with socio-demographic profile, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Mini International Neuropsychiatric Interview, and Postgraduate Institute Neuroticism Scale. STATISTICAL ANALYSIS: For statistical analysis, descriptive statistics, group comparisons, and Pearson's product moment correlations were carried out. Factor analysis and cluster analysis were done to determine the factor structure and subtypes of "Dhat syndrome." RESULTS: A diagnostic and assessment instrument for "Dhat syndrome" has been developed and the phenomenology in 100 patients has been described. Both the health beliefs scale and associated symptoms scale demonstrated a three-factor structure. The patients with "Dhat syndrome" could be categorized into three clusters based on severity. CONCLUSIONS: There appears to be a significant agreement among various stakeholders on the phenomenology of "Dhat syndrome" although some differences exist. "Dhat syndrome" could be subtyped into three clusters based on severity. PMID- 27385846 TI - A case-control study of psychological distress in survivors of farmers' suicides in Wardha District in central India. AB - CONTEXT: Lack of literature on psychological aspects of survivors of farmers' suicides is hurdle in devising effective helping strategies for rising number of survivors across the country. AIMS AND OBJECTIVES: To assess the psychological distress and its correlates in survivors of farmers' suicides. SETTINGS AND DESIGN: Case-control study design was used in Wardha District of Vidarbha region in the central India. MATERIALS AND METHODS: A predesigned and pretested semistructured questionnaire was used to assess sociodemographic variables. Self Reporting Questionnaire-20 was used to evaluate psychological distress in 98 survivors of farmers' suicides and 98 age, sex, and occupation-matched controls. STATISTICAL ANALYSIS: Significance of differences between case and control groups were assessed using Chi-square test or Fisher's two-tailed exact test for class variables. For continuous variables, Student's t-test was used P < 0.05 was considered significant. RESULTS: Significantly higher proportion of survivors had psychological distress than controls. Female survivors, spouse and parents of suicide victims had a high risk of distress. Psychological distress was commonly expressed by depressive and somatic symptoms. CONCLUSIONS: Survivors of farmers' suicides are suffering from significant psychological distress. PMID- 27385845 TI - Suicide in hospitalized early psychosis patients at the time of discharge from hospital: An exploratory study of attempters and nonattempters. AB - BACKGROUND: Early intervention programs for psychosis are gateways for suicide prevention. These programs offer an excellent opportunity for prevention due to easy access, early identification, and provisions for continuity of care. These programs have been found effective in reducing rates of suicide after discharge to communities. The objective of this study was to examine suicide risk level among early psychosis patients admitted with and without previous suicide attempts. We hypothesized that all patients admitted with early psychosis would be at high risk of suicide, regardless of a previous suicide attempt. METHODOLOGY: Suicide risk was compared between patients admitted with a suicide attempt (n = 30) and patients admitted without a suicide attempt (n = 30). The primary outcome measure of interest was suicide risk which was measured with the Scale for Impact of Suicidality-Management, Assessment and Planning of Care clinical interview. All patients met DSM-IV TR criteria for schizophrenia. Psychopathology was assessed using the Brief Psychiatric Rating Scale and level of depression was assessed using the Hamilton Depression Rating Scale. The data were statistically analyzed. RESULTS: Patients admitted with a previous attempt (mean = 29.5, standard deviation [SD] =12.0) did not differ significantly in suicide risk from those admitted without a previous attempt (mean = 27.5, SD = 12.5), (t[58] =0.63, P = 0.53). Patients admitted without a suicide attempt scored higher in depressive symptoms (t[58] =10.62, P < 0.001) than that of admitted with a suicide attempt. There were no significant differences between patients admitted with and without suicide attempts on any comorbidity, other than a trend toward a higher prevalence of personality disorder in patients with no suicide attempt. Attempters and nonattempters did not differ on any demographic variables either. CONCLUSIONS: Of those admitted without a previous suicide attempt, our findings suggest that it is critical that all patients discharged from an acute psychiatric unit must receive comprehensive community care. The identification of risk, and subsequent intervention for suicidal and self-harm behaviors, should be a central part of treatment for all mental disorders. PMID- 27385847 TI - A novel approach in the detoxification of intravenous buprenorphine dependence. AB - BACKGROUND: Opioid dependence remains a significant problem in India, and of late intravenous (IV) buprenorphine use has increased in India, especially in combination with antihistamines and benzodiazepines. Its usage has many serious consequences in the form of needle-transmitted hepatitis and HIV, which is showing an increasing trend. Buprenorphine is a partial agonist at MU-opioid receptors. In tablet form (and rarely as IV), it is widely used in the treatment of opioid detoxification. We assessed the safety and efficacy of transdermal patch of buprenorphine with week long duration of action in the treatment of detoxification of IV buprenorphine dependence in view of its many advantages. MATERIALS AND METHODS: Six consecutive patients with International Classification of Diseases diagnosis of Opioid Dependence Syndrome (IV buprenorphine) were given a buprenorphine patch for treatment of withdrawal symptoms after receiving consent. Severity of opioid dependence was assessed by using Severity of Opioid Dependence Questionnaire on the day of presentation. Subjective and objective rating for opioid withdrawal was done by subjective opiate withdrawal scale (SOWS) and objective opiate withdrawal scale (OOWS) prepatch and postpatch 3(rd) and 7(th) day. Buprenorphine side effect checklist was applied on a daily basis. RESULTS: The patients had a mean age of 30 years, of whom 83.3% are males. All were educated and 50% were currently employed. All of them had additional comorbid substance use as well as a comorbid psychiatric diagnosis. Each of them received a patch of varying dosage. The patch dose used initially was based on clinical considerations alone and was fairly adequate in controlling acute withdrawal symptoms. There is a significant improvement in SOWS and OOWS while comparing the baseline (prepatch) with 3(rd) and 7(th) day (postpatch) (P <= 0.05). None of the patients reported any side effect with the patch. CONCLUSION: This study shows that transdermal buprenorphine is safe, useful, and clinically effective, and a 7-day application may provide an alternative means of detoxification. However, the result of the study needs to be replicated in a larger sample in a clinical setting, and a control group receiving a conventional mode of treatment needs to be included. PMID- 27385848 TI - Alcohol use among school-going adolescent boys and girls in an industrial town of Assam, India. AB - BACKGROUND: Some people in Northeast India prepare rice-based alcoholic drinks in the household. People use these drinks in religious and social functions, and these are taken even in the presence of parents and elders. Easy access to illicit substances in industrial towns and lack of social inhibition for intake of homemade alcohol might increase the vulnerability of youth to these habits. OBJECTIVE: To estimate the prevalence of alcoholic drink user among school-going adolescent students in an industrial town of Assam. MATERIALS AND METHODS: A cross-sectional survey was designed to collect the data using a predesigned questionnaire. Personal interview was conducted to collect the data about pattern of alcohol use, type of alcoholic drinks they use, duration, and information about parents and peer. Data were analyzed using Epi-info 17 and Statistical Package for Social Sciences-17.0 (Chicago, USA, SPSS Inc.). RESULTS: About 36% out of 1285 students have tasted/used homemade alcoholic drinks (HADs) and 12.3% used commercially available alcoholic drinks (CADs). Significantly higher numbers (P < 0.001) of adolescent students (>=15 years) used CAD in comparison to children (<15 years). However, the number of younger students was higher in using HAD. Minimum age at first experience of CAD was 7 years and that of HAD was 4 years; the duration varied from 1 to 8 years and 1-15 years, respectively. Parent's behavior of taking tobacco and/or alcohol influenced the habit of their children. Father's habit was found to be associated with male offspring's habit of taking CAD. About 16% of the students used one or more substances along with alcohol. CONCLUSION: High percentage of adolescents in the industrial town of Assam use alcoholic drinks with a male preponderance. They taste alcoholic drinks at a very young age. Parent's indulgence in taking tobacco, alcohol, or both was found to influence higher intake by their offspring. PMID- 27385849 TI - Prevalence of premenstrual syndrome and premenstrual dysphoric disorder among college students of Bhavnagar, Gujarat. AB - BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS) characterized by mood changes, anxiety, and somatic symptoms experienced during the specific time of menstrual cycle. Prevalence data of PMS and PMDD is sparse among college girls in India. AIMS: The aim of this study is to study the prevalence of PMS and PMDD among college students of Bhavnagar (Gujarat), its associated demographic and menstrual factors, to rank common symptoms and compare premenstrual symptom screening tool (PSST) with Structured Clinical Interview for DSM-IV-TR defined PMDD (SCID-PMDD) for sensitivity and specificity. MATERIALS AND METHODS: A cross-sectional survey was done in five colleges of Bhavnagar. Of 529 subjects approached, 489 college girls were finally analyzed for sociodemographic data, menstrual history, and PSST. SCID-PMDD was applied among those who were positive on PSST and 20% of those who were negative. The data were analyzed using OpenEpi Version 2. Chi-square test was done for qualitative variables and analysis of variance for quantitative variables. Sensitivity, specificity, and predictive values were calculated for PSST. RESULTS: The prevalence of PMS was 18.4%. Moderate to severe PMS was 14.7% and PMDD was 3.7% according to DSM IV-TR and 91% according to International Classification of Diseases, 10(th) edition criteria. The symptoms commonly reported were "fatigue/lack of energy," "decrease interest in work," and "anger/irritability." The most common functional impairment item was "school/work efficiency and productivity." PSST has 90.9% sensitivity, 57.01% specificity, and 97.01% predictive value of negative test. CONCLUSION: Prevalence of PMS among college students is similar to other studies from Asia. PSST is a useful screening tool for PMS, and it should be confirmed by more specific tool as by SCID-PMDD. Routine screening with PSST can identify college girls who can improve with treatment. PMID- 27385850 TI - A review of reception order in the management of mentally ill persons in a psychiatric institute. AB - BACKGROUND: Mentally ill prisoners, when requiring admission in a psychiatric facility, have to be admitted only by a reception order of a judicial magistrate and convicts by warrants issued by the Government to jail superintendents and the superintendent of the hospital. Both can be only under Section 27 of The Mental Health Act, 1987. MATERIALS AND METHODS: A study of the contents of reception order and warrants regarding the acts and section under which they were issued over 1 year period for the admission of the patients in the criminal ward of the Institute of Mental Health was carried out. RESULTS: Only three reception orders quoted Section 27 out of 54 patients admitted under a reception order. Nineteen patients were admitted by the jail superintendents. DISCUSSION: Various issues that were found in the reception order and their consequences are discussed, and a possible response to these issues is mooted. CONCLUSION: Almost none of the reception orders were found to be proper. This deficit needs to be rectified by sensitizing the various authorities. PMID- 27385851 TI - Substance use and criminality among juveniles-under-enquiry in New Delhi. AB - BACKGROUND: There is an intimate relationship between drugs and criminal behavior. The drug-violence relationship is further complicated by intoxicating doses and/or withdrawal effects of specific drugs. Understanding this relationship is important for both healthcare workers and policy makers. MATERIALS AND METHODS: The study was conducted in Prayas observation home for boys, a short stay home for juveniles-under-enquiry in New Delhi. The present study aims to correlate substance use and criminal behavior by investigating the sociodemographic characteristics and the current trend of substance use among juveniles in New Delhi. In this study, 487 detained juveniles aged between 8 and 18 years were included. The information was obtained by face-to-face semi structured interviews and juvenile case records maintained by the juvenile home. RESULTS: Out of 487 juveniles-under-enquiry booked under different crimes, 86.44% of the sample had a history of substance use. Consumption of tobacco and cannabis were higher when compared to other drugs. Consumption of psychotropic drugs though relatively lesser was related with more serious crimes. There is an increasing trend in serious crimes such as rape, murder/attempt to murder, and burglary committed by juveniles. Drug-crime correlation has been noted among consumption of cannabis with murder, inhalants with rape and opioids with snatching-related crimes. CONCLUSION: Substance use and criminal behavior are clearly interrelated. Greater the involvement in substance abuse, more severe is the violence and criminality. This paper highlights this complex relationship and suggests possible scope of interventions. PMID- 27385852 TI - Frequency and pattern of radiological and laboratory investigations in patients with mental illnesses: A study from North Rajasthan. AB - BACKGROUND: There are widespread perceptions that excessive and unnecessary investigations are done in many patients with mental illnesses. There are no studies from India looking into this issue. AIMS: (i) To study the frequency and pattern of various investigations such as electroencephalography (EEG), computerized tomography (CT) scan of head, magnetic resolution imaging (MRI) scan of brain, and blood investigations carried out by the previous doctors on patients seeking treatment in three different settings. (ii) To study the socio demographic and clinical correlates of investigations carried out on these patients. STUDY DESIGN AND SETTINGS: A cross-sectional study in a community outreach clinic, a district level psychiatric hospital, and psychiatry outpatient clinic of a medical college. MATERIALS AND METHODS: 160 newly registered patients seeking treatment at these settings were assessed using a semi-structured pro forma regarding various investigations that they had undergone before seeking the current consultation. Frequency of investigations was analyzed. RESULTS: About 47.5% of patients had at least one of the three brain investigations done. EEG, CT head, and MRI brain had been done in 37.5%, 20.0%, and 8.8% of the patients, respectively. Only 1.8% of the patients had blood tests done before current consultation. CONCLUSION: This study results raise question whether certain investigations such as EEG and CT head were carried out excessively and blood investigations were done infrequently. Further studies on larger samples with prospective study design to evaluate the appropriateness of current practices of carrying out investigations in patients presenting with psychiatric symptoms are required. PMID- 27385853 TI - Effect of age and anticonvulsants on seizure threshold during bilateral electroconvulsive therapy with brief-pulse stimulus: A chart-based analysis. AB - BACKGROUND: Efficacy and adverse effects of electroconvulsive therapy (ECT) depend on the extent to which the electrical stimulus exceeds patients' seizure thresholds (STs). Titration method of estimating ST is recommended. Age and co prescribed anticonvulsants (ACs) are known to affect ST. Literature on ST in bilateral ECT (BLECT) is sparse. OBJECTIVE: To explore the clinical and demographic determinants of ST in a clinically representative sample of patients prescribed with BLECT. MATERIALS AND METHODS: ECT records of 640 patients who received BLECT in 2011 in an academic psychiatric setting were studied. Demographic, clinical, pharmacological, and ECT details were analyzed. As per the standard practice, during the 1(st) ECT session, ST was determined by titration method, starting with 30 milli-Coulombs (mC) and increasing by 30 mC and thence in steps of 60 mC. Increase in ST over up to 6(th) session of ECT was noted. Receiver operating characteristic curve was used to find age cut-off with high specificity for ST >=120 mC. The associations of ST and increase in ST with the age cut-off and other clinical factors were assessed using Chi-square test and logistic regression analysis. RESULTS: The mean age was 30.98 years (+11.23 years) and mean ST at 1(st) ECT session was 130.36 mC (+51.96 mC). There was significantly high positive correlation (r = 0.37, P < 0.001) between age and ST. Cut-off age of 45 years had high specificity: Only 4.6% of those older than 45 years had ST <120 mC. Higher proportion of patients on AC had ST >=120 mC. These associations were seen even after controlling for potential confounds of each other using logistic regression analysis. The results were similar for increase in ST over the course of ECT. Sex, diagnosis, use of antipsychotics, antidepressants, lithium, and benzodiazepines (BZPs) had no effect on ST or its increase. CONCLUSIONS: For BLECT using brief-pulse stimulus, ST depends on age and use of AC. For patients above the age of 45 years, ST estimation may be started at 120 mC with least risk of using unduly higher stimulus. Other medications including BZPs have little influence on ST. PMID- 27385854 TI - Early effects of modern electroconvulsive therapy on subjective memory in patients with mania or depression. AB - CONTEXT: Although electroconvulsive therapy (ECT) is considered a very effective tool for the treatment of psychiatric diseases, memory disturbances are among the most important adverse effects. AIMS: This study aimed to assess prospectively early subjective memory complaints in depressive and manic patients due to bilateral, brief-pulse ECT, at different stages of the treatment, compare the associations between psychiatric diagnosis, sociodemographic characteristics, and ECT characteristics. SETTINGS AND DESIGN: This prospective study was done with patients undergoing ECT between November 2008 and April 2009 at a tertiary care psychiatry hospital of 2000 beds. MATERIALS AND METHODS: A total of 140 patients, scheduled for ECT with a diagnosis of bipolar disorder (depressive or manic episode) or unipolar depression according to Diagnostic and Statistical Manual of Mental Disorders IV diagnostic criteria, were included in the study and invited to complete the Squire Subjective Memory Questionnaire (SSMQ) before ECT, after the first and third sessions and end of ECT treatment. STATISTICAL ANALYSIS: Mean values were compared with the Kruskal-Wallis test and comparison of the longitudinal data was performed with a nonparametric longitudinal data analysis method, F1_LD_F1 design. RESULTS: SSMQ scores of the patients before ECT were zero. SSMQ scores showed a decrease after the first and third ECT sessions and before discharge, showing a memory disturbance after ECT and were significantly less severe in patients with mania in comparison to those with depression. CONCLUSIONS: These findings suggest an increasing degree of subjective memory complaints with bilateral brief-pulse ECT parallel to the increasing number of ECT sessions. PMID- 27385855 TI - "Why not psychiatry??" Interns of a medical college in Northern Kerala responds. AB - PURPOSE: This study is to assess the attitude of the medical interns toward psychiatry, psychiatrists and patients with mental health problems. MATERIALS AND METHODS: A personal data sheet and the Balon et al. questionnaire was used to assess the attitude among medical interns (n = 44) of a medical college in Northern Kerala. RESULTS: There was modestly good attitude toward psychiatry throughout the study. Data were compared between interns who have completed their posting in psychiatry and those who have not. There was no significant difference except for their awareness about consultation liaison services and the authoritative power of psychiatrists in mental health field. The stigma toward psychiatry is on the decline at least among medical professionals, and more interns are interested in taking up psychiatry as a future specialty. CONCLUSION: Although the study has evidenced a positive attitude to psychiatry, there is still room to improve. A clearer picture could be attained by conducting similar studies in a bigger sample size. A structured curriculum and compulsory internship during the undergraduate course have greatly contributed toward building a more positive opinion of the subject. PMID- 27385856 TI - Impact of differences in psychiatry curriculum of undergraduate medical and physiotherapy students on their attitude towards psychiatry. AB - BACKGROUND: Negative attitude toward psychiatry (ATP) among medical students is a serious concern. Some studies have concluded that after training in the subject, attitude changes toward positive side. Currently in India, medical students have a less intense course without separate exam or binding to attend training whereas physiotherapy students have more intense course with separate subject exam and binding to attend training in psychiatry. OBJECTIVE: To ascertain and compare the positive and negative ATP in final year MBBS students and final year physiotherapy (BPTh) students who have completed psychiatry curriculum. METHODS: This is a cross-sectional study with semi-structured pro forma for sociodemographic variables and ATP-30 questionnaire to evaluate ATP of 94 medical and physiotherapy students each. Nonparametric methods were used for statistical analysis with appropriate tests of significance and P value was set at 0.05. RESULTS: Mean ATP-30 score for medical students was 91.9 (standard deviation [SD] =7.0) and that of physiotherapy students was 105.8 (SD = 9.7), this difference in two groups was highly significant (Kruskal-Wallis H = 81.3, df = 1, P < 0.001). Of all medical students, 36 (41.4%) had negative attitude while only 2 (2.1%) of the physiotherapy students had negative ATP (chi(2) = 41.7, P < 0.001). Boys were 2.6 times more likely to have negative ATP than girls (relative risk = 2.6, P = 0.005). CONCLUSIONS: Physiotherapy students with intense and planned training in psychiatry as an exam subject have significantly more positive ATP than medical students. PMID- 27385857 TI - How bad was unmodified electroconvulsive therapy! A retrospective study. AB - "Unmodified"-electroconvulsive therapy (ECT) being considered unethical remained away from the scientific literature, but continued in practice in many parts of the world. The Mental Health Care Bill, 2011, proposed for its banning in India. The aim of this study is to retrospectively observe "how bad was unmodified-ECT" to the patients in a naturalistic setting. The study was done at the Central Institute of Psychiatry, India. Files of patients receiving unmodified ECT during 1990-1995 were retrospectively reviewed. Outcome was evaluated in terms of desired effectiveness and the side effects as noted in the files by the treating team. Six hundred and thirty-seven patients (6.94% of total admission) received ECT with meticulous standard-of-care except provision of anesthesia. Satisfactory improvement was noted in 95.45% patients with no noticeable/reported complication in 89.05%. Premature termination of ECT for complications occurred in 2.19% patients. "Unmodified"-ECT, though unethical, still could ensure favorable outcome with proper case selection and meticulous standard-of-care. PMID- 27385858 TI - Effect of yoga practices in reducing counterproductive work behavior and its predictors. AB - CONTEXT: Aggression and negative affectivity (NA) are known for moderating relationship between job stressors and counterproductive work behavior. Yoga has been demonstrated earlier to reduce the parameters of aggression and negative emotions. AIM: The present study examined the effectiveness of yoga practices in reducing counterproductive work behavior and its predictors such as aggression and NA. SETTINGS AND DESIGN: A pretest-posttest randomized controlled design. MATERIALS AND METHODS: The study sample included yoga group (n = 80) and control group (n = 80). Yoga module that included asanas, pranayama, meditation, and yogic theory were taught to the yoga group. Mild to moderate physical exercises and management theories were taught to the control group. Both groups received intervention for 10 weeks, covering 1 h daily, 5 days a week. Measurements of self-reported counterproductive work behaviors, aggression, and NA were taken as baseline and postintervention for assessment. RESULTS: Yoga group reported significant reductions in aggression, NA, and counterproductive work behavior in comparison with the control group after 10 weeks. CONCLUSIONS: This study contributes by introducing a cost-effective way to prevent the heavy losses organizations are incurring due to counterproductive work behavior and its predictors. The findings support that yoga at workplace may result in positive psychological empowerment of the employees as well. PMID- 27385859 TI - Dermatitis artifacta of tongue: A rare case report. AB - Dermatitis artifacta is a psychiatric disorder in which the patient deliberately produces self-inflicted skin lesions to satisfy an unconscious psychological or emotional need, often a desire to receive medical treatment. We present a case of a 20-year-old female with pain in abdomen, pain during urination, and multiple skin lesions, mostly in the reach of her dominant hand and in tongue. She gave a history of several episodes of similar illnesses with admission in various hospitals. She was improved with selective serotonin reuptake inhibitor, supportive and insight-oriented psychotherapy. PMID- 27385860 TI - Indian psychiatric society initiated travel fellowship training in psychiatry: A unique opportunity for young psychiatrists. PMID- 27385861 TI - The Burgholzli Hospital: Its history and legacy. AB - The Burgholzli Hospital Zurich has a very important place in history, as part of of modern era in Psychiatry. Founded in 1870 by the efforts of Griesinger, it was here many eminent path breakers in Psychiatry like Bleuler, Jung, Adolf Meyer and others once worked. From here, Bleuler coined the term "Schizophrenia". Now the University Hospital of Zurich, Burgholzli's transformation from a mental hospital to a centre of excellence speaks of a rich legacy. It is a model worth emulating in many parts of the world. PMID- 27385862 TI - Manimekalai: The ancient Buddhist Tamil epic, its relevance to psychiatry. AB - This article refers to materials of psychiatric interest found in the Manimekalai written by the 2(nd) Century CE Buddhist poet Sathanar. From the early description of a wandering psychotic in the streets of Pukar, the ancient maritime capital of the Cholas it is opined that this description fits that of present-day schizophrenia. A drunkard making fun of a Jain monk and a cross dressed individual are also found in the same streets. Manimekalai's request to the Chola king to convert the prison to a place of piety with Buddhist monks is mentioned. Lord Buddha's teachings on the compassionate way of life are presented. PMID- 27385863 TI - Oxcarbazepine - induced hyponatremia in bipolar disorder: A report of two cases. PMID- 27385864 TI - Cannabinoid hyperemesis syndrome as an unusual cause of cyclic vomiting. PMID- 27385865 TI - WhatsApp addiction and borderline personality disorder: A new therapeutic challenge. PMID- 27385866 TI - Erratum: Author's reply. AB - [This corrects the article on p. 329 in vol. 57, PMID: 26600599.]. PMID- 27385867 TI - Pandemic of Publications and Predatory Journals: Another Nail in the Coffin of Academics. PMID- 27385868 TI - Doctors for Tribal Areas: Issues and Solutions. AB - Health parameters of tribal population had always been a concern for India's march towards Millennium development Goals (MDG's). Tribal population contributes 8.6% of total population, in spite of efforts and commitment of Government of India towards MGD, India lagged far behind from achieving and optimal health of tribal population will be a concern for achieving Sustainable development Goals SDG's also. Some of the common health problems of the tribal population face are deficiency of essential components in diet like energy malnutrition, protein calorie malnutrition and micronutrient deficiencies. Goiter, Gastrointestinal disorders, particularly dysentery and parasitic infections are very common. High prevalence of genetic disorders like sickle cell anemia and others are endemic in few tribes of India. Tribal Health is further compounded issues by social issues like excessive consumption of alcohol, poor access to contraceptive, substance abuse and gender based violence. Besides other reasons, like poor budget allocation, difficult to reach, poor access to health care facility, severe shortage of qualified health workers and workforce led to poor governance of health sector in tribal areas. Present view point reflects on the issues of inadequacy of doctors in tribal area and suggests possible solutions. PMID- 27385869 TI - Twin Studies: A Unique Epidemiological Tool. AB - Twin studies are a special type of epidemiological studies designed to measure the contribution of genetics as opposed to the environment, to a given trait. Despite the facts that the classical twin studies are still being guided by assumptions made back in the 1920s and that the inherent limitation lies in the study design itself, the results suggested by earlier twin studies have often been confirmed by molecular genetic studies later. Use of twin registries and various innovative yet complex software packages such as the (SAS) and their extensions (e.g., SAS PROC GENMOD and SAS PROC PHREG) has increased the potential of this epidemiological tool toward contributing significantly to the field of genetics and other life sciences. PMID- 27385870 TI - Evaluation of Skill-oriented Training on Enhanced Syndromic Case Management (ESCM) of Reproductive Tract Infections / Sexually Transmitted Infections (RTI/STIs) of Care Providers from Three-tier Health-care System of Gujarat. AB - BACKGROUND: Enhanced syndromic case management (ESCM) deals with reproductive tract and sexually transmitted infections. Capacity building of service providers not only boosts the program but also inputs from them improve the quality of services. OBJECTIVES: To (1) identify problem areas from providers' perspectives and the gaps in knowledge and application and (2) assess the gains (if any) through pre and post-training evaluation. MATERIALS AND METHODS: A total of 121 participants (medical/para medical) from various medical colleges, district/sub district hospitals/ community health centers, and urban dispensaries across Gujarat were trained at a teaching institute. Trainings were of 2-3 days duration involving different learning methodology. Pre- and post-training evaluation were done on a designed pro forma and data were entered in MS office Excel 2007. Gains in knowledge/skills if any were assessed by comparing pre-/post-evaluation responses and applying test of significance (x(2) test). OBSERVATIONS: Out of total 121 participants, half (60) were doctors and the rest were paramedics [staff nurse (SN) and lab technicians (LT)]. Doctors revealed significant gain in basics of reproductive tract infections (RTI) and sexually transmitted infections (STI), syndrome identification, STI/HIV co-infection, and ESCM and less gain in asymptomatic STI/ complications, vulnerability, male reproductive organs, causes of vaginal/urethral discharge, STI complications, cervical cancer screening, and limitation of syndromic management. Gain was statistically significant in basics of RTI/STI amongst adolescent in paramedics; lab technicians showed significant gain in knowledge of laboratory-related areas. CONCLUSION: Assessment revealed (1) poor baseline knowledge and (2) gains following training sometimes significant and other times not significant even in core areas. Quality monitoring and contents/ methodologies modification are essential for robust trainings. Gains in skills could not be assessed through this evaluation. PMID- 27385871 TI - Correlates of the Use of Different Tobacco Cessation Methods by Smokers and Smokeless Tobacco Users According to Their Socio-Demographic Characteristics: Global Adult Tobacco Survey (GATS) India 2009-10. AB - BACKGROUND: Tobacco control has two aspects. One involves preventing non-tobacco users from using tobacco and the second involves tobacco cessation (quitting) by existing tobacco users. There are various methods of tobacco cessation. Pharmacotherapy [e.g., nicotine replacement therapy (NRT) and medications such as bupropion] and behavioral counselling are some of the internationally approved methods of tobacco cessation. OBJECTIVE: This paper intends to study how age, gender, residence (rural/urban), education, and occupation influence the use of various tobacco cessation methods by smokers and smokeless tobacco users. MATERIALS AND METHODS: The study was a cross-sectional secondary data analysis of the Global Adult Tobacco Survey (GATS) India 2009-2010. There were 3725 smokers and 6354 smokeless tobacco users included in the study who made attempts to quit in the 12 months prior to the survey by use of different cessation methods (NRT, drugs such as bupropion, counselling, and other methods). RESULTS: A significant association was demonstrated between increasing educational attainment and use of cessation methods for all the methods among smokers. Being employed (Govt. or non Govt.) was positively associated with the use of NRT as a cessation method by smokers. Students and homemakers had higher odds of using pharmacotherapy methods among smokers. A significant association was demonstrated for the gender and age of tobacco users with the use of counselling as a cessation method among smokeless tobacco users. CONCLUSION: The findings of this study have important implications for tobacco cessation service providers in view of supporting their decision of choosing a particular tobacco cessation method for tobacco users according to certain kinds of sociodemographic characteristics. PMID- 27385872 TI - Evaluation of Pharmacists' Services for Dispensing Emergency Contraceptive Pills in Delhi, India: A Mystery Shopper Study. AB - BACKGROUND: Although emergency contraceptive pills are available over the counter, the quality of consultation, including key areas of contraceptive counseling and prevention of sexually transmitted infections (STI), has not been well documented. OBJECTIVE: To evaluate actual pharmacist services while dispensing emergency contraception through a mystery shopper technique. MATERIAL AND METHODS: This cross-sectional study was conducted in 81 pharmacies situated in Delhi by 4 trained mystery shoppers posed as customers over a period of 6 months. RESULTS: None of the pharmacists asked about the time lapsed since last unprotected sexual intercourse or last menstrual period before deciding the eligibility of the customer. The majority were unclear about side effects associated with emergency contraception (78.57%) or with anticipated changes in menstrual flow (78.57%); 85.71% did not know whether subsequent unprotected intercourse would be protected. Only 15.71% counseled shoppers regarding risk of STI on asking leading questions and 88.5% did not provide any contraceptive advice. CONCLUSION: There is a huge gap in the technical knowledge and mindset of the pharmacists when it comes to checking for the eligibility of the client and providing advice regarding use of regular contraception and barrier for protection from STI, which needs to be addressed in order to realize the full benefit of making emergency contraceptive pills available over the counter. PMID- 27385873 TI - Intimate Partner Violence: Associated Factors and Acceptability of Contraception Among the Women. AB - OBJECTIVE: To determine the prevalence of various types of domestic violence and to find out the impact of intimate partner violence (IPV) on adoption of contraceptive measures among the women who are victim to this. MATERIALS AND METHODS: This questionnaire-based, cross-sectional study was conducted in the department of obstetrics and gynecology of a tertiary care hospital in Delhi. Four hundred and one postpartum females were randomly selected over a period of 5 months and were questioned about their age, parity, educational status, occupation, husband's education, monthly family income, and, if present, IPV in detail. These study participants were enquired about their contraceptive knowledge and use. RESULTS: Sexual violence was seen in 38.4% of the cases, physical violence in 22.4% of the cases, and verbal abuse was seen in nearly 32.7% of the cases. In response to any of the three violence faced, only 23 women (11.79%) reacted by discussing with parents and friends. In 4.61% of the cases, the violence was so severe that she had to inform police. This study showed that higher percentage of women without IPV accepted immediate postpartum contraception methods as compared to those with IPV (35.9% vs. 25%, P = 0.023), but the overall frequency of using contraceptive methods was higher in those with IPV as compared to those without IPV (49% vs. 47%, P = 0.690). CONCLUSION: IPV is associated with increased contraceptive adoption. PMID- 27385874 TI - Profiles and Factors Associated with Poor Glycemic Control Among Inpatients with Diabetes Mellitus Type 2 as a Primary Diagnosis in a Teaching Hospital. AB - CONTEXT: Diabetes mellitus is a growing health problem in most countries. In Malaysia, there was an increase in prevalence over the years. This makes diabetes also a growing concern in Malaysia, which warrants strengthening of the prevention and control programme. AIMS: This paper aims to describe the profiles of diabetes mellitus type 2 in tertiary setting and to identify the risk factors for high level of HbA1c among the study population. The findings will give a glimpse on current status of diabetes in our country and may reflect the achievement of the country in combating this disease. SETTINGS AND DESIGN: A cross-sectional study was conducted in UKM Medical Centre. METHODS AND MATERIAL: Medical records of patient with E11 ICD-10 code were collected using Case Report Form. STATISTICAL ANALYSIS USED: Descriptive analysis done of mean and median while test of association were done using Spearman correlation and logistic regression. RESULTS: The results showed that majority of inpatients of DMT2 showed mean age of 58.8 + 12.6 years and most were males (56.7%) with secondary level of education (41.7%). Median duration of disease was 12.0 + 11.0 years with median HbA1c level of 8.9 +/- 4.4%. Only small proportion of patients achieved the desired level of HbA1c <6.5% (21.3%) and significant association was found with tertiary level of education [AOR = 0.10, 95%CI = 0.01-0.96] and with type of anti-diabetic therapy [AOR = 15.90, 95%CI=1;2.03-124.30]. CONCLUSIONS: In conclusion, diabetes mellitus type 2 inpatients still showed unsatisfactory glycemic control and holistic approach using health education should be advocated continuously in the future in view of education being one of the predictors for the good HbA1c outcome. PMID- 27385875 TI - Evaluation of Antenatal to Neonatal Continuum Care Services Affecting Neonatal Health in a Tertiary Health-Care Setup. AB - BACKGROUND: Maternal and child mortality and morbidity continue to be high despite existence of various national health programmes in India. Annually 41% of all Under 5 mortality is comprised of neonates, 3/4 of who die within the first week of life. Even though effective programmes are existing, optimum utilization is still a question. So the present study was planned to assess utilisation of maternal and neonatal health services and its influence on neonatal health. OBJECTIVES: 1. To assess the utilization of MCH services before admission to SNCU. 2. To analyse the process of implementation of IMNCI before referral and during the admission. 3. To observe the impact on neonatal health and give necessary recommendations. METHODOLOGY: The information regarding utilization of MCH services was obtained by conducting in depth interviews with the responsible adults accompanying the sick neonate. The Pre-treatment and referral slips were verified and compared with that of the prescribed guidelines laid down by the IMNCI for young infants (0-2 months) at SNCU. RESULTS AND DISCUSSION: Some of the important observations were mentioned here. 100% women had TT immunization whereas 72% had the full ANC, 58.7% had full course of IFA, 76% had utilized JSY benefits and 48.34% had their PNC. 84% neonates had required immunization, 59.01% were on exclusive breast feeding. 38.9% were paid home visits, only 42% had an idea about the danger signs of neonatal period. 23% sick babies were treated under IMNCI guideline. Among them 98% given initial treatment, only 34% given proper diagnosis/classification, 56% were given adequate advice. PMID- 27385876 TI - Seniors' Recreation Centers in Rural India: Need of the Hour. AB - AIM: To empower and bring the underprivileged senior citizens in the rural areas to the mainstream of life through setting up of model "senior citizens' recreation centers" that can be replicated in the other parts of the country. MATERIALS AND METHODS: Six senior citizens' recreation centers are run in six villages under a community health program of a leading Medical College in South India, which were started by looking into their perceived needs and in a location where organized self-help women groups (SHGs) showed willingness to take the role of caretakers. Together there are 140 members in 6 centers and the most deserving members were identified using a participatory rural appraisal (PRA) method. These centers are open for 5 days a week and the main attraction of the center has been provision of one good, wholesome, noon-meal a day, apart from several recreational activities. The members were also assessed for chronic energy deficiency (CED) and quality of life at the beginning of enrolment using body mass index (BMI) and WHO-BREF scale. RESULTS: The attendance to these centers was nearly 90% of the enrolled beneficiaries. A statistically significant improvement was noticed in quality of life in the physical, psychological, social, and environmental domain (P < 0.05). There was also a significant increase in the average BMI after 1 year of the intervention (P < 0.05). CONCLUSION: Care of underprivileged senior citizens is a growing need in the rural areas and the "Recreation centers" proved to be a beneficial model that can be easily replicated. PMID- 27385877 TI - Dietary Calcium Intake, Serum Calcium Level, and their Association with Preeclampsia in Rural North India. AB - BACKGROUND: Preeclampsia in pregnancy has been shown to be associated with low serum calcium level. Though the evidence is abundant, it is equivocal. OBJECTIVES: The study aimed to estimate the dietary calcium intake and serum calcium status among pregnant women, and to document the association of the dietary calcium intake and serum calcium status with incidence of preeclampsia in the 3rd trimester of pregnancy. MATERIALS AND METHODS: A community-based cross sectional study was conducted in the Health and Demographic Surveillance System (HDSS) site, Ballabgarh, Haryana, India. All pregnant women between 28 weeks and 36 weeks of gestation were interviewed. A semi-structured interview schedule and a 24-h dietary recall questionnaire were administered to assess the dietary calcium intake. AutoAnalyser (Biolis 24i) was used for measuring serum calcium. RESULTS: We enrolled 217 pregnant women. The mean [standard deviation (SD)] dietary calcium intake was 858 (377) mg/day. The mean (SD) serum calcium level was 9.6 mg/dL (0.56). Incidence of preeclampsia was 13.4%. Preeclampsia was not associated with hypocalcemia [odds ratio (OR) = 1.2 95% confidence interval (CI); 0.27-3.98]. CONCLUSION: The majority of pregnant women had inadequate dietary calcium intake. The prevalence of hypocalcemia was low. Low serum calcium level was not associated with preeclampsia. Calcium supplementation may not reduce preeclampsia in this population. PMID- 27385878 TI - Adaptation of Locally Available Portion Sizes for Food Frequency Questionnaires in Nutritional Epidemiological Studies: How Much Difference does it Make? AB - INTRODUCTION: There is need for employing strategies to minimize measurement errors while administering semi-quantitative FFQ. The current study was planned to adapt and standardize locally available portion sizes for semi-quantitative FFQ to improve its validity and document the process of standardization of portion sizes. METHODOLOGY: The study was conducted in 9 villages of the INCLEN SOMAARTH DDESS (Demographic, Development and Environmental Surveillance Site), Palwal district, Haryana, India. The subjects in these nine villages are part of a cohort study to assess the interaction between societal and household factors with food intake and physical activity of children. Systematic utensil survey was undertaken in 3 randomly chosen households per village i.e. 27 households and the portion sizes were derived from a total of 74 serving utensils. The derived sizes were classified as small (240 ml), medium (320 ml) and large (600 ml). The semi quantitative FFQ with locally derived portion sizes was then administered to 63 children in 6-12 year age group. RESULTS: The volume of food measured by the reference portion sizes generally being employed in the national surveys, would have been underestimated the food consumed by the child by 55-60% as compared to what was being consumed by the children in the study area. The correlation between food intake assessed by 24-hr recall method and FFQ using derived (local) portion sizes was better as compared to that obtained with the semi-quantitative FFQ done with reference portions. CONCLUSION: In conclusion, local portion size adaptation of FFQ for semi-quantification is useful to mitigate measurement errors associated with this technique. PMID- 27385879 TI - Patient Safety in Obstetrics and Gynecology Departments of two Teaching Hospitals in Delhi. AB - BACKGROUND: A healthy safety culture is integral to positive health care. A sound safety climate is required in Obstetrics and Gynecology to prevent adverse outcomes. OBJECTIVE: The objective of this study was to assess and compare patient safety culture in two departments of Obstetrics and Gynecology. MATERIALS AND METHODS: Using a closed-ended standard version of Hospital Survey on Patient Safety Culture (HSOPS), respondents were asked to answer 42 survey items, grouped into 10 dimensions and two outcome variables in two tertiary care teaching hospitals in Delhi. Qualitative data were compared using Fisher's exact test and chi-square test wherever applicable. Mean values were calculated and compared using unpaired t-test. RESULTS: The overall survey response rate was 55%. A positive response rate of 57% was seen in the overall perception of patient safety that ranged from very good to acceptable. Sixty-four percent showed positive teamwork across hospital departments and units, while 36% gave an affirmative opinion with respect to interdepartmental handoffs. However, few adverse events (0-10) were reported in the last 12 months and only 38% of mistakes by doctors were reported. Half of the respondents agreed that their mistakes were held against them. There was no statistical difference in the safety culture between the two hospitals. CONCLUSIONS: Although the perception of patient safety and standards of patient safety were high in both the hospitals' departments, there is plenty of scope for improvement with respect to event reporting, positive feedback, and nonpunitive error. PMID- 27385880 TI - Why do Patients in Pre-Anti Retroviral Therapy (ART) Care Default: A Cross Sectional Study. AB - BACKGROUND AND OBJECTIVES: Approximately, 40% of the patients registered in the National AIDS Control Program in India are not on antiretroviral therapy (ART), i.e., are in pre-ART care. However, there are scarce data regarding the retention of pre-ART patients under routine program conditions. The main objective of this study was to find out the reasons for default among patients in pre-ART care. MATERIALS AND METHODS: Patients enrolled in the ART Centre, Banaras Hindu University (BHU) between January and December 2009 and in pre-ART care were included in the study. Defaulters were those pre-ART patients who missed their last appointment of CD4 count by more than 1 month. Defaulters were traced telephonically in 2011 and those who returned and gave their consent for the study were interviewed using a semi-structured questionnaire. RESULTS: Out of 620 patients in pre-ART care, 384 (68.2%) were defaulters. One hundred forty-four of the defaulters were traced and only 83 reached the ART center for interview. Among defaulters who did not reach the ART center, illiterate and unmarried were significantly more and mean duration from registration to default was also significantly less as compared to those who came back for the interview. Most defaulters gave more than one reason for defaulting that were as follows: Inconvenient clinic timings (98%), need for multiple mode of transport (92%), perceived improved health (65%), distance of center from home (61%), lack of social support (62%), and financial difficulty (59%). INTERPRETATION AND CONCLUSION: Active tracing of pre-ART patients through outreach and strengthening of the Link ART centers will improve the retention of patients in the program. PMID- 27385881 TI - IAPSM World Health Day 2016 Quiz Report. PMID- 27385882 TI - Developing a personalized treatment model based on molecular biomarkers and imaging in breast cancer: Has the time come? PMID- 27385883 TI - 2-(fluorine-18)-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography after breast conserving surgery: Correlation with molecular markers of breast cancer. AB - AIM: To investigate the role of 2-(fluorine-18)-fluoro-2-deoxy-D-glucose ((18)F FDG) positron emission tomography/computed tomography (PET/CT) early after breast conserving surgery (BCS) in patients with breast cancer (BC) and whether we can determine which molecular biomarkers of breast carcinoma put the patients at risk. MATERIALS AND METHODS: This retrospective study involved 88 patients with histologically proven T1 or T2 BC, who were treated with BCS and underwent (18)F FDG PET/CT study. The correlation between biological markers (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 [HER2], and Ki 67) of the primary tumor and (18)F-FDG PET/CT findings was analyzed. RESULTS: (18)F-FDG PET/CT demonstrated the presence of BC disease (locoregional disease [LRD], distant metastases, or contralateral BC) in 26 of 88 patients (29.5%). Regarding immunohistochemical profiles, BC expressing high levels of Ki-67 were associated with an increased percentage of LRD, which was the major recurrence pattern on (18)F-FDG PET/CT. Although the BC disease was observed more commonly in patients with HER2 positivity compared to those of HER2 negative, the difference did not reach statistical significance. The patients with T2 tumor or a higher histopathological grade had a higher percentage of BC disease. CONCLUSIONS: This study demonstrated that patients with early stage BC treated with BCS have a remarkable risk of the presence of BC even early after surgery, and there was a clinically important relationship between (18)F-FDG PET/CT findings and biological markers of BC. These findings suggest that high-risk molecular biomarkers (Ki-67, HER2) can be taken into account in the decision making the process for both preoperative imaging and planning of the surgical approach. PMID- 27385884 TI - Impact of sweating on equivalent dose of patients treated with (131)Iiodine. AB - BACKGROUND: Radioiodine therapy is used for the treatment of patients with differentiated thyroid cancer (DTC) who undergo total thyroidectomy. After radioiodine administration, regulations require to quarantine these patients until their retained activity reduces to <33 mCi. Some of the injected radioiodine is excreted by perspiration which helps dose reduction so that performing the activities which stimulate sweating such as exercise may shorten the time of dose reduction. To the best of our knowledge, this is the first study in the literature that has evaluated the impact of specific exercise program on the ambient equivalent dose of (131)I gamma rays. MATERIALS AND METHODS: Patients with DTC without metastasis who had undergone total thyroidectomy and were treated with radioiodine were included in this study. 30 patients were chosen among patients who were able to exercise, did not have renal failure, and did not use diuretics. Patients were divided into two control and intervention groups. Intervention group members walked on treadmills under a specific program, in 3 time intervals. The control group did not have any specific activity. Immediately after each exercise process, both groups took a shower, and their doses were measured by a survey dosimeter. RESULTS: It was revealed that there was a significant difference between mean values before and after each exercise time. The calculated P value which evaluates the overall impact was 0.939 which revealed that there was no significant difference between total ambient equivalent dose reductions of both groups. CONCLUSION: According to the study, it may conclude that sweating is an effective alternative way for radioiodine excretion, and if sweating is accompanied with well-hydrated status they may have synergism effect to shorten quarantine period. This could be an important consideration in patients which over-hydration is intolerable especially those with cardiac, liver, or renal problems. PMID- 27385885 TI - Therapeutic applications of radioactive (131)iodine: Procedures and incidents with capsules. AB - BACKGROUND: Treatments for thyrotoxicosis and carcinoma thyroid are carried out by oral administration of radioactive iodine ((131)I) in the form of liquid or capsules. The liquid form of (131)I has higher risk factors such as vapourization, spillage and need for management of higher activity wastes. Use of (131)I in capsule form simplify procedures of handling compared to liquid form of (131)I. The guidelines of safe handling and quality assurance aspects for therapeutic use (131)I are well outlined by International Atomic Energy Agency (IAEA) reports. AIM: A few unusual incidents with I-131 capsules encountered in the past need to be highlighted from health physics point of view. MATERIALS AND METHODS: In Royal Hospital, Oman, I-131 is imported in capsules, and the total activity handled/year steadily increased over 10 years. Discrete activities range from 185 MBq (5 mCi) up to 7.4 GBq (200 mCi). In four incidents deviations in standard operational procedures were recorded. RESULTS: Nature of incidents is described as follows: (1) After assay of activity, the capsule was directly put in the lead container with missing of inner cap. (2) Patient poured water in the Perspex tube, when the capsule was handed over to her, making an emergency situation. (3) In 3 high activity capsules (2 nos 2.96 GBq, 1 no. 4.26 GBq), observed sticky behavior in capsule holder on the 2(nd) day post receipt, which were in order on the 1(st) day. (4) A capsule could not be swallowed by a patient, which was taken back from the mouth. Monitoring of patient later did not show residual ingested activity. CONCLUSIONS: The report documents some of the unusual incidents for information to other centers engaged in such radioactive administrations. PMID- 27385886 TI - Micronucleus frequencies in groups receiving external or internal radiation. AB - OBJECTIVE: In the current study, we aimed to explore whether there is alteration between pre- and post-treatment micronucleus (MN) frequencies induced by internal and external ionizing radiation. MATERIALS AND METHODS: The study enrolled a total of 67 patients including patients admitted to our hospital for treatment of hyperthyroidism (n = 17), scanning with low-dose I-131 (n = 15), and ablative therapy with high-dose I-131 (n = 15) at Department of Nuclear Medicine as well as patients with different diagnoses receiving external radiotherapy with various doses and durations at Department of Radiation Oncology (n = 20). Thirty-two patients who received radioactive iodine and returned for a follow-up visit at 1 month. RESULTS: Considering both pre- and post-treatment MN frequencies of each group, lowest MN frequencies were detected for patients undergoing screening with low-dose I-131, and highest MN frequencies were found in radiotherapy patients. Comparison of pre- and post-treatment MN frequencies among hyperthyroidism, when pre- and post-treatment MN frequencies compared among hyperthyroidism, I-131 whole body scanning, ablation, and radiotherapy patient groups differences between MN frequencies were significant for each group (P < 0.05). CONCLUSION: Our study showed that MN analysis might be of value in determining chromosome damage that could potentially occur in patients exposed to internal and external radiation. PMID- 27385887 TI - Metastatic mimics on bone scan: "All that glitters is not metastatic". AB - In this pictorial review, cases where benign diseases caused a diagnostic dilemma on bone scan are illustrated. This review highlights the value of correlative imaging- single-photon emission computed tomography/computed tomography (CT), CT, and magnetic resonance imaging in solving the diagnostic problem by exact localization and characterization of the lesions. All these eventually lead to increased diagnostic confidence, better and more accurate reporting and avoidance of delay in initiation of treatment due to equivocal results. The imaging features of these benign pathologies - which are "mimics of metastatic disease," are elaborated so that the reader can incorporate them while reporting so as to avoid mis-interpretations. PMID- 27385888 TI - Usefulness of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in dermatofibrosarcoma protuberans on treatment with imatinib. AB - Dermatofibrosarcoma protuberans (DFSP) is a rare locally aggressive tumor with distant metastases being unusual. We present a case of metastatic DFSP treated with imatinib showing complete metabolic response to treatment. PMID- 27385889 TI - Primary pulmonary lymphoma-role of fluoro-deoxy-glucose positron emission tomography-computed tomography in the initial staging and evaluating response to treatment - case reports and review of literature. AB - Primary pulmonary lymphoma (PPL) is an uncommon entity of non-Hodgkin lymphoma, which accounts for <1% of all cases of lymphoma. We present two rare cases of PPL of diffuse large B-cell lymphoma, which underwent (18)fluorine fluoro-deoxy glucose positron emission tomography-computed tomography for initial staging and response evaluation after chemotherapy. PMID- 27385890 TI - A case of sarcoidosis diagnosed by positron emission tomography/computed tomography. AB - Sarcoidosis is a multisystem granulomatous disorder of unknown cause which may affect any organ or system but primarily involve the lungs and the lymphatic system. Extrapulmonary sarcoidosis represents approximately 30-50% of patients. We report the case of a 51-year-old female who presented with increasing complaints of a cough, weakness, weight loss, and chest pain and who was found to have a suspicious lesion on thorax computed tomography(CT). Fluorodeoxyglucose (FDG) positron emission tomography/CT performed for diagnostic purposes demonstrated increased FDG accumulation at the bilateral enlarged parotid and lacrimal gland and in the reticulonodular infiltration area located in the left lung as well as multiple lymphadenopathies with increased FDG accumulation. There were also hepatosplenomegaly and splenic uptake. Skin biopsy showed noncaseating granulomas, and the patient was diagnosed as stage 2 sarcoidosis. PMID- 27385891 TI - Unusual case of infantile fibrosarcoma evaluated on F-18 fluorodeoxyglucose positron emission tomography-computed tomography. AB - Infantile fibrosarcoma (IFS) is a rare soft-tissue sarcoma originating from extremities and occasionally from axial soft tissue. The prognosis is good with favorable long-term survival. It is rarely metastasizing tumor, the chances being lesser with IFS originating from extremities. Use of neoadjuvant chemotherapy (NACT) as a treatment regime further reduces the chances of local relapse and distant metastasis. The organs commonly affected in metastatic IFS are lungs and lymph nodes. We report an unusual case of an IFS originating from extremity, which received NACT, yet presented with an early metastatic disease involving soft tissues and sparing lungs and lymph nodes, as demonstrated on fluorodeoxyglucose positron emission tomography-computed tomography. PMID- 27385892 TI - Late metastatic recurrence of penile carcinoma after 10 years: Demonstration with (18)F-fluorodeoxyglucose positron emission tomography/computed tomography. AB - Penile cancer is rare cancer. While inguinal and pelvic nodal metastasis is common, distant metastasis is rare. We here present the interesting case of a 59 year-old male patient with penile carcinoma, previously treated with penectomy and inguinal lymphadenectomy 10 years earlier. He presented with bone pains and given history of malignancy he was referred for an (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT). PET/CT demonstrated multiple (18)F-FDG avid bone and lung metastases. No locoregional disease was seen. Biopsy from a lung nodule confirmed the diagnosis, and the patient was started on palliative chemotherapy. PMID- 27385893 TI - Utility of (18)F-choline photon emission tomography/computed tomography in the diagnosis of parathyroid adenoma. AB - Recently, the role of (18)F-choline in the detection of parathyroid adenomas has been reported. At our institution, we are currently studying the role of this tracer in comparison to the standard methoxy-isobutyl-isonitrile.(MIBI) scan with single photon emission tomography/computed tomography. Our initial results show that (18)F-choline is at least as good as 99mTc-MIBI scan. We present here a representative case of a 45-year-old woman with multiple skeletal lytic lesions and a high parathyroid hormone.(PTH) who underwent both these imaging techniques with concordant results, further confirmed by histopathology and postoperative fall in serum PTH levels. PMID- 27385894 TI - A case report of hyperfunctioning metastatic thyroid cancer and rare I-131 avid liver metastasis. AB - Thyroid cancer is usually, relatively hypofunctional; most patients with thyroid cancer are clinically euthyroid. The combination of thyroid cancer and thyrotoxicosis is not common. We herein, report a case of follicular thyroid cancer with hyperfunctioning metastasis in a 43-year-old woman who presented with thyrotoxicosis, a cold right thyroid nodule, and low I-131 uptake at the thyroid bed. An additional total body scan with I-131 revealed a large radioiodine avid osteolytic bone metastasis with soft tissue masses and liver metastasis. The patient received treatment with total thyroidectomy, methimazole, and I-131 at a cumulative dose of 600 mCi along with recombinant human thyroid-stimulating hormone before the first I-131 treatment and palliative radiation. The patient had normal liver function test and experienced a mild degree of bone marrow suppression after I-131. At the 2-year follow-up, the patient was still alive with the progression of bone metastases but was doing well with less severe thyrotoxicosis, good ambulation, and an Eastern Cooperative Oncology Group performance status of 2. Clinicians should be aware of the unusual concurrent presentation of thyrotoxicosis and thyroid cancer, a differential diagnosis in patients with thyrotoxicosis and low or normal radioiodine uptake over the neck and also potential pitfalls during radionuclide treatment. PMID- 27385895 TI - A rare case of extensive skeletal muscle metastases in adenocarcinoma cervix identified by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography scan. AB - Adenocarcinoma cervix is an uncommon histological subtype of carcinoma cervix; further incidence of skeletal muscle metastases is even rarer. We report the identification of extensive fluorodeoxyglucose (FDG) avid metastatic skeletal muscle deposits in a known case of adenocarcinoma cervix. The largest lesion representative of muscle deposit in the right deltoid was histopathologically confirmed to be metastatic poorly differentiated carcinoma. This report also serves to highlight the importance of (18)F-FDG positron emission tomography/computed tomography (CT) as compared to conventional imaging modalities such as CT and ultrasonography and comments better over the description of invasiveness as well as the extent of disease in carcinoma cervix. PMID- 27385896 TI - Rare case of thoracic kidney detected by renal scintigraphy. AB - Intrathoracic kidney is a rare congenital abnormality with lowest frequency among all renal ectopias. Patients with thoracic kidneys are usually asymptomatic, and the condition is usually discovered incidentally during radiological evaluation for other conditions or during thoracic surgery. We report a case of a 62-year old male who was referred to our department for renal scintigraphy for a nonvisualized left kidney on ultrasonography report. Both Tc-99m dimercaptosuccinic acid and diethylenetriaminepentaacetic acid scans revealed a left thoracic kidney which was confirmed by CT scan of the thorax and abdomen. PMID- 27385897 TI - Metastasis in urothelial carcinoma mimicking prostate cancer metastasis in Ga-68 prostate-specific membrane antigen positron emission tomography-computed tomography in a case of synchronous malignancy. AB - Prostate cancer is the second most common cancer in man. It commonly presents with urinary symptoms, bone pain, or diagnosed with elevated prostate-specific antigen.(PSA) levels. Correct staging and early diagnosis of recurrence by a precise imaging tool are the keys for optimum management. Molecular imaging of prostate cancer with Ga-68 prostate-specific membrane antigen.(PSMA), positron emission tomography-computed tomography.(PET-CT) has recently received significant attention and frequently used with a signature to prostate cancer specific remark. However, this case will highlight the more cautious use of it. A 72-year-old male treated earlier for synchronous double malignancy.(invasive papillary urothelial carcinoma right ureter and carcinoma prostate) presented with rising PSA.(0.51.ng/ml) and referred for Ga-68 PSMA PET-CT, which showed a positive enlarged left supraclavicular lymph node. Lymph node biopsy microscopic and immunohistochemistry examination revealed metastatic carcinoma favoring urothelial origin. Specificity of PSMA scan to prostate cancer has been seen to be compromised in a certain situation mostly due to neoangiogenesis, and false positives emerged in renal cell cancer, differentiated thyroid cancer, glioblastoma, breast cancer brain metastasis, and paravertebral schwannomas. Understanding the causes of false positive will further enhance the confidence of interpretating PSMA scans. PMID- 27385898 TI - Compression type stress fracture of femoral neck with equivocal X-ray features diagnosed on (99m)Tc-MDP SPECT/CT in a case of trivial hip pain. AB - Stress insufficiency fracture is usually diagnosed clinically and on the basis of routine X-ray imaging findings. However, the absence of any known predisposing factors and negative or occult radiographic findings pose diagnostic challenges. We report the case of an elderly male patient who presented with a chief complaint of trivial left hip pain and with equivocal radiographic findings. Triphasic (99m)Tc-methylene diphosphonate bone scan and single-photon emission computed tomography/computed tomography helped in arriving at the diagnosis of stress insufficiency fracture involving femoral neck. PMID- 27385899 TI - Intrathoracic toxic thyroid nodule causing hyperthyroidism with a multinodular normal functional cervical thyroid gland. AB - Radionuclide scintigraphy with I-131 and Tc-99m pertechnetate ((99)mTc04) has been widely used in detecting toxic nodules. Intrathoracic goiter usually presents as an anterior mediastinal mass. Mostly the connection between intrathoracic mass and the cervical thyroid gland is clearly and easily identified occurring as a result of inferior extension of thyroid tissue in the neck, which is called as secondary intrathoracic goiter. Completely separated, aberrant or in other words primary intrathoracic goiters arise as a result of abnormal embryologic migration of ectopic thyroid closely associated with aortic sac and descend into the mediastinum. Intrathoracic goiters are generally nontoxic nodules existing with mass effect without causing hyperthyroidism. However, mostly reported cases had enlarged thyroid glands in the neck. This report demonstrates the usefulness of I-131 and (99)mTc04 scintigraphy for detecting intrathoracic goiter causing hyperthyroidism with a normal functioned cervical thyroid gland. PMID- 27385900 TI - Renal metastasis from papillary carcinoma thyroid detected by whole body iodine scan: A case report and review of the literature. AB - Papillary carcinoma is the most common thyroid malignancy. Usual sites of metastasis include lungs and bone, but renal metastasis is very rare. Here we present a case of a follicular variant of papillary carcinoma with renal and lung metastasis at presentation. PMID- 27385901 TI - Role of FDG PET/CT in Baastrup's disease. AB - Baastrup's disease is a benign condition, which presents as chronic low back pain. It is also known as "kissing spine syndrome" and refers to close approximation of adjacent spinous processes producing inflammation and back pain. This condition is often misdiagnosed, resulting in incorrect treatment and persistence of symptoms. Diagnosis of Baastrup's disease is verified with clinical examination and imaging studies. Conventionally, clinicians resort to magnetic resonance imaging (MRI) of spine rather than X-ray or computed tomography (CT) in the evaluation of back pain. MRI can additionally identify flattening, sclerosis, enlargement, cystic lesions, and bone edema at the articulating surfaces of the two affected spinous processes. Studies have reported that (18)Fluorine fluorodeoxyglucose-positron emission tomography/CT (FDG-PET/CT) can detect a bursitis or an inflammation as a form of stress reaction despite a negative MRI and (99m)Tc Methylene diphosphonate (MDP) bone scan. PET/CT is usually not a recommended investigation for this condition. However, this case report highlights the benefit of FDG-PET/CT in identifying the site of inflammatory pathology. It is also known to identify the exact site of inflammation where steroid or local anesthetic injection can be administered to alleviate pain, especially in patients with multilevel vertebral involvement. PMID- 27385902 TI - 18F-fluorodeoxyglucose positron emission tomography-computed tomography finding of left gonadal vein thrombosis in a case of renal cell carcinoma. AB - Tumor thrombus from renal cell carcinoma is commonly reported in renal vein and inferior vena cava with a few reports of gonadal vein involvement. Here, we report a case of an elderly female who underwent fluorodeoxyglucose (FDG) positron emission tomography-computed tomography scan for initial staging of left renal cell carcinoma. Along with an FDG avid left renal mass lesion, scan also revealed FDG avid tumor thrombus in the entire length of the left gonadal vein. PMID- 27385903 TI - Objective improvement in renal function post-Dietl's crisis: Documented on renal dynamic scintigraphy. AB - Dietl's crisis is one of the treatable causes of intermittent abdominal pain. The pain is due to acute hydronephrosis that leads to stretching of the pelvis. The most common cause of this intermittent hydronephrosis is aberrant renal vessel at lower pole that causes pelvi-ureteric junction obstruction.(PUJO). High insertion of the ureter is one of the other rare causes. We present a case of 5-year-old boy with intermittent abdominal pain and distension with ultrasonography features of gross left hydronephrosis. Renal dynamic scan.(RDS) with ethylene dicysteine showed negligible functioning left kidney. On third follow-up day, the patient passed a lot of urine with decrease in abdominal pain and distension. Then, again the patient was sent to us 8.days after the first study for repeat RDS, which showed significant improvement in function and decreased in the size of left kidney though with persistent PUJO. On exploration high insertion of the ureter at pelvis was found to be the cause and was treated. PMID- 27385904 TI - Bilateral generalised synovial chondromatosis of the knee: Bone scintigraphic demonstration with radiologic correlation. AB - A 67-year-old woman with a history of bilateral progressive knee pain and swelling was referred for (99m)Tc-methyl diphosphonate bone scintigraphy. Flow and blood pool images showed bilateral heterogeneous increased uptake and delayed phase revealed mass-looking lobulated heterogeneous increased activity in both of knees extending distal part of the femoral shaft, but no other pathologic uptake was found in rest of the body. A diagnosis of synovial chondromatosis was made when correlated with X-ray and computed tomography.(CT) images. This is a rare presentation of generalized synovial chondromatosis involving both knees which demonstrated on bone scintigraphy with X-ray and CT correlation. PMID- 27385905 TI - Importance of assessing nonattenuation-corrected positron emission tomography images in treatment response evaluation of primary cutaneous lymphoma. AB - Studies have shown previously that nonattenuated corrected (AC) positron emission tomography (PET) images improve detection of superficial lesions when compared to AC images. We present a case of cutaneous lymphoma to demonstrate the importance of assessing nonattenuation-corrected PET images in treatment response evaluation. PMID- 27385906 TI - Depiction of ventriculoperitoneal shunt obstruction with single-photon emission computed tomography/computed tomography. AB - An 83-year-old male patient with ventriculoperitoneal shunt underwent radionuclide shunt study using single-photon emission computed tomography/computed tomography (SPECT/CT) to evaluate the shunt patency. The planar images showed activity at the cranial region and spinal canal but no significant activity at the peritoneal cavity. However, SPECT/CT images clearly demonstrated accumulation of activity at the superior part of bifurcation level with no activity at the distal end of shunt as well as no spilling of radiotracer into the peritoneal cavity indicating shunt obstruction. SPECT/CT makes the interpretation of radionuclide shunt study more accurate and easier as compared with traditional planar images. PMID- 27385907 TI - Left lobe hypoplasia of thyroid with right lobe ectopia: Radionuclide thyroid scan and ultrasonographic correlation. PMID- 27385908 TI - Dopamine transporter single-photon emission computed tomography brain scan: A reliable way to distinguish between degenerative and drug-induced parkinsonism. PMID- 27385909 TI - An Integrated Approach for RNA-seq Data Normalization. AB - BACKGROUND: DNA copy number alteration is common in many cancers. Studies have shown that insertion or deletion of DNA sequences can directly alter gene expression, and significant correlation exists between DNA copy number and gene expression. Data normalization is a critical step in the analysis of gene expression generated by RNA-seq technology. Successful normalization reduces/removes unwanted nonbiological variations in the data, while keeping meaningful information intact. However, as far as we know, no attempt has been made to adjust for the variation due to DNA copy number changes in RNA-seq data normalization. RESULTS: In this article, we propose an integrated approach for RNA-seq data normalization. Comparisons show that the proposed normalization can improve power for downstream differentially expressed gene detection and generate more biologically meaningful results in gene profiling. In addition, our findings show that due to the effects of copy number changes, some housekeeping genes are not always suitable internal controls for studying gene expression. CONCLUSIONS: Using information from DNA copy number, integrated approach is successful in reducing noises due to both biological and nonbiological causes in RNA-seq data, thus increasing the accuracy of gene profiling. PMID- 27385910 TI - Role of Biomarkers in the Diagnosis, Risk Assessment, and Management of Pulmonary Hypertension. AB - Pulmonary hypertension is a severe and debilitating disease with no definite cure, and the domain of targeted therapies is a promising field for better management of this severe condition. The disease comprises pulmonary arterial remodeling, hypoxia, endothelial dysfunction, and inflammation, with subsequent organ damage including right heart and liver dysfunction. Biomarkers have a valuable role at different levels of the disease, from diagnosis to risk assessment and management, in order to decrease the burden of the disease in terms of both morbidity and mortality. PMID- 27385911 TI - S2M: A Stochastic Simulation Model of Poliovirus Genetic State Transition. AB - Modeling the molecular mechanisms that govern genetic variation can be useful in understanding the dynamics that drive genetic state transition in quasispecies viruses. For example, there is considerable interest in understanding how the relatively benign vaccine strains of poliovirus eventually revert to forms that confer neurovirulence and cause disease (ie, vaccine-derived poliovirus). This report describes a stochastic simulation model, S2M, which can be used to generate hypothetical outcomes based on known mechanisms of genetic diversity. S2M begins with predefined genotypes based on the Sabin-1 and Mahoney wild-type sequences, constructs a set of independent cell-based populations, and performs in-cell replication and cell-to-cell infection cycles while quantifying genetic changes that track the transition from Sabin-1 toward Mahoney. Realism is incorporated into the model by assigning defaults for variables that constrain mechanisms of genetic variability based roughly on metrics reported in the literature, yet these values can be modified at the command line in order to generate hypothetical outcomes driven by these parameters. To demonstrate the utility of S2M, simulations were performed to examine the effects of the rates of replication error and recombination and the presence or absence of defective interfering particles, upon reaching the end states of Mahoney resemblance (semblance of a vaccine-derived state), neurovirulence, genome fitness, and cloud diversity. Simulations provide insight into how modeled biological features may drive hypothetical outcomes, independently or in combination, in ways that are not always intuitively obvious. PMID- 27385912 TI - Toward a Learning Health-care System - Knowledge Delivery at the Point of Care Empowered by Big Data and NLP. AB - The concept of optimizing health care by understanding and generating knowledge from previous evidence, ie, the Learning Health-care System (LHS), has gained momentum and now has national prominence. Meanwhile, the rapid adoption of electronic health records (EHRs) enables the data collection required to form the basis for facilitating LHS. A prerequisite for using EHR data within the LHS is an infrastructure that enables access to EHR data longitudinally for health-care analytics and real time for knowledge delivery. Additionally, significant clinical information is embedded in the free text, making natural language processing (NLP) an essential component in implementing an LHS. Herein, we share our institutional implementation of a big data-empowered clinical NLP infrastructure, which not only enables health-care analytics but also has real time NLP processing capability. The infrastructure has been utilized for multiple institutional projects including the MayoExpertAdvisor, an individualized care recommendation solution for clinical care. We compared the advantages of big data over two other environments. Big data infrastructure significantly outperformed other infrastructure in terms of computing speed, demonstrating its value in making the LHS a possibility in the near future. PMID- 27385913 TI - Increasing Tumor Accessibility with Conjugatable Disulfide-Bridged Tumor Penetrating Peptides for Cancer Diagnosis and Treatment. AB - Tumor-homing peptides with tissue-penetrating properties increase the efficacy of targeted cancer therapy by delivering an anticancer agent to the tumor interior. LyP-1 (CGNKRTRGC) and iRGD (CRGDKGPDC) are founding members of this class of peptides. The presence of the cysteines forming the cyclizing disulfide bond complicates conjugation of these peptides with other molecules, such as drugs. Here, we report the synthesis of conjugatable disulfide-bridged peptides and their conjugation to biologically important molecules. We have synthesized the LyP-1, iRGD, and CRGDC (GACRGDCLGA) peptides with a cysteine or maleimidohexanoic acid added externally at N-terminus of the sequences. Subsequent conjugation to payloads yielded stable compounds in which the tumor-homing properties of the peptide and the biological activity of the payload were retained. PMID- 27385914 TI - The Effects of the UK Pregnancies Better Eating and Activity Trial Intervention on Dietary Patterns in Obese Pregnant Women Participating in a Pilot Randomized Controlled Trial. AB - OBJECTIVE: The objective of this study is to investigate the effects of the UK Pregnancies Better Eating and Activity Trial (UPBEAT) behavioral intervention on dietary patterns in obese pregnant women. METHODS: Dietary patterns were derived from Food Frequency Questionnaires using principal component analysis in 183 UPBEAT pilot study participants. RESULTS: Two unhealthy dietary patterns, processed and traditional, predominantly characterized by foods high in sugar and fat, improved [processed -0.54 (-0.92 to -0.16), P = 0.006 and traditional -0.83 (-1.20 to -0.45), P < 0.001] following the intervention, while a cultural pattern that was found to be associated with the Black African/Caribbean participants did not change [-0.10 (-0.46 to 0.26), P = 0.589]. CONCLUSION: Unhealthy dietary patterns are evident in obese pregnant women. The UPBEAT intervention was effective in improving maternal dietary patterns; however, obese pregnant women from minority ethnic groups may be less receptive to intervention. PMID- 27385916 TI - Subclinical LV Dysfunction Detection Using Speckle Tracking Echocardiography in Hypertensive Patients with Preserved LV Ejection Fraction. AB - BACKGROUND: Early detection of subclinical left ventricular (LV) systolic dysfunction in hypertensive patients is important for the prevention of progression of hypertensive heart disease. METHODS: We studied 60 hypertensive patients (age ranged from 21 to 49 years, the duration of hypertension ranged from 1 to 18 years) and 30 healthy controls, all had preserved left ventricular ejection fraction (LVEF), detected by two-dimensional speckle tracking echocardiography (2D-STE). RESULTS: There was no significant difference between the two groups regarding ejection fraction (EF) by Simpson's method. Systolic velocity was significantly higher in the control group, and global longitudinal strain was significantly higher in the control group compared with the hypertensive group. In the hypertensive group, 23 of 60 patients had less negative global longitudinal strain than -19.1, defined as reduced systolic function, which is detected by 2D-STE (subclinical systolic dysfunction), when compared with 3 of 30 control subjects. CONCLUSION: 2D-STE detected substantial impairment of LV systolic function in hypertensive patients with preserved LVEF, which identifies higher risk subgroups for earlier medical intervention. PMID- 27385915 TI - Targeting MAPK Signaling in Age-Related Macular Degeneration. AB - Age-related macular degeneration (AMD) is a major cause of irreversible blindness affecting elderly people in the world. AMD is a complex multifactorial disease associated with demographic, genetics, and environmental risk factors. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in the pathogenesis of AMD. The mitogen-activated protein kinase (MAPK) signaling pathways are activated by diverse extracellular stimuli, including growth factors, mitogens, hormones, cytokines, and different cellular stressors such as oxidative stress. They regulate cell proliferation, differentiation, survival, and apoptosis. This review addresses the novel findings from human and animal studies on the relationship of MAPK signaling with AMD. The use of specific MAPK inhibitors may represent a potential therapeutic target for the treatment of this debilitating eye disease. PMID- 27385917 TI - Impaired Sarcoplasmic Reticulum Calcium Uptake and Release Promote Electromechanically and Spatially Discordant Alternans: A Computational Study. AB - Cardiac electrical dynamics are governed by cellular-level properties, such as action potential duration (APD) restitution and intracellular calcium (Ca) handling, and tissue-level properties, including conduction velocity restitution and cell-cell coupling. Irregular dynamics at the cellular level can lead to instabilities in cardiac tissue, including alternans, a beat-to-beat alternation in the action potential and/or the intracellular Ca transient. In this study, we incorporate a detailed single cell coupled map model of Ca cycling and bidirectional APD-Ca coupling into a spatially extended tissue model to investigate the influence of sarcoplasmic reticulum (SR) Ca uptake and release properties on alternans and conduction block. We find that an intermediate SR Ca uptake rate and larger SR Ca release resulted in the widest range of stimulus periods that promoted alternans. However, both reduced SR Ca uptake and release promote arrhythmogenic spatially and electromechanically discordant alternans, suggesting a complex interaction between SR Ca handling and alternans characteristics at the cellular and tissue level. PMID- 27385918 TI - "C.R.E.A.T.E."-ing Unique Primary-Source Research Paper Assignments for a Pleasure and Pain Course Teaching Neuroscientific Principles in a Large General Education Undergraduate Course. AB - A large (250 registrants) General Education lecture course, Pleasure and Pain, presented basic neuroscience principles as they related to animal and human models of pleasure and pain by weaving basic findings related to food and drug addiction and analgesic states with human studies examining empathy, social neuroscience and neuroeconomics. In its first four years, the course grade was based on weighted scores from two multiple-choice exams and a five-page review of three unique peer-reviewed research articles. Although well-registered and well received, 18% of the students received Incomplete grades, primarily due to failing to submit the paper that went largely unresolved and eventually resulted in a failing grade. To rectify this issue, a modified version of the C.R.E.A.T.E. (Consider, Read, Elucidate hypotheses, Analyze and interpret data, Think of the next Experiment) method replaced the paper with eight structured assignments focusing on an initial general-topic article, the introduction-methods, and results-discussion of each of three related peer-review neuroscience-related articles, and a final summary. Compliance in completing these assignments was very high, resulting in only 11 INC grades out of 228 students. Thus, use of the C.R.E.A.T.E. method reduced the percentage of problematic INC grades from 18% to 4.8%, a 73% decline, without changing the overall grade distribution. Other analyses suggested the students achieved a deeper understanding of the scientific process using the C.R.E.A.T.E. method relative to the original term paper assignment. PMID- 27385919 TI - Illuminating the Undergraduate Behavioral Neuroscience Laboratory: A Guide for the in vivo Application of Optogenetics in Mammalian Model Organisms. AB - Optogenetics is a technology that is growing rapidly in neuroscience, establishing itself as a fundamental investigative tool. As this tool is increasingly utilized across the neuroscience community and is one of the primary research techniques being presented at neuroscience conferences and in journals, we believe that it is important that this technology is introduced into the undergraduate neuroscience research laboratory. While there has been a significant body of work concentrated to deploy optogenetics in invertebrate model organisms, little to no work has focused on brining this technology to mammalian model organisms in undergraduate neuroscience laboratories. The establishment of in vivo optogenetics could provide for high-impact independent research projects for upper-level undergraduate students. Here we review the considerations for establishing in vivo optogenetics with the use of rodents in an undergraduate laboratory setting and provide some cost-saving guidelines to assist in making optogenetic technologies financially accessible. We discuss opsin selection, cell-specific opsin expression strategies, species selection, experimental design, selection of light delivery systems, and the construction of implantable optical fibers for the application of in vivo optogenetics in rodents. PMID- 27385921 TI - Breadboard Amplifier: Building and Using Simple Electrophysiology Equipment. AB - Electrophysiology is a valuable skill for the neuroscientist, but the learning curve for students can be steep. Here we describe a very simple electromyography (EMG) amplifier that can be built from scratch by students with no electronics experience in about 30 minutes, making it ideal for incorporating into a laboratory activity. With few parts and no adjustments except the gain, students can begin physiology experiments quickly while having the satisfaction of having built the equipment themselves. Because the output of the circuit goes to a computer sound card, students can listen to electrophysiological activity as they see it on the computer screen, a feature many of our students greatly appreciated. Various applications are discussed, including dual channel recording, using streaming media platforms with remote lab partners and acquiring data in the field on a smart phone. Our students reported that they enjoyed being able to build a working device and using it to record from their own muscles. PMID- 27385920 TI - Evaluation of Changes in Ghanaian Students' Attitudes Towards Science Following Neuroscience Outreach Activities: A Means to Identify Effective Ways to Inspire Interest in Science Careers. AB - The scientific capacity in many African countries is low. Ghana, for example, is estimated to have approximately twenty-three researchers per a million inhabitants. In order to improve interest in science among future professionals, appropriate techniques should be developed and employed to identify barriers and correlates of science education among pre-university students. Young students' attitudes towards science may affect their future career choices. However, these attitudes may change with new experiences. It is, therefore, important to evaluate potential changes in students' attitudes towards science after their exposure to experiences such as science outreach activities. Through this, more effective means of inspiring and mentoring young students to choose science subjects can be developed. This approach would be particularly beneficial in countries such as Ghana, where: (i) documented impacts of outreach activities are lacking; and (ii) effective means to develop scientist-school educational partnerships are needed. We have established an outreach scheme, aimed at helping to improve interaction between scientists and pre-university students (and their teachers). Outreach activities are designed and implemented by undergraduate students and graduate teaching assistants, with support from faculty members and technical staff. Through this, we aim to build a team of trainee scientists and graduates who will become ambassadors of science in their future professional endeavors. Here, we describe an approach for assessing changes in junior high school students' attitudes towards science following classroom neuroscience outreach activities. We show that while students tended to agree more with questions concerning their perceptions about science learning after the delivery of outreach activities, significant improvements were obtained for only two questions, namely "I enjoy science lessons" and "I want to be a scientist in the future." Furthermore, there was a generally strong trend towards a change in attitude for questions that sought information about students' perceptions about scientists (both positive and negative perceptions). In addition, outreach providers reported that their involvement in this public engagement scheme helped them acquire several transferable skills that will be beneficial in their studies and career development. These include vital skills in project and time management, teamwork and public speaking. Altogether, our findings provide novel indications that the development of scientist-school outreach partnerships in Ghana has valuable implications for science education and capacity development. PMID- 27385923 TI - Lights! Camera! Action Projects! Engaging Psychopharmacology Students in Service based Action Projects Focusing on Student Alcohol Abuse. AB - Alcohol abuse continues to be an issue of major concern for the health and well being of college students. Estimates are that over 80% of college students are involved in the campus "alcohol culture." Annually, close to 2000 students die in the United States due to alcohol-related accidents, with another 600,000 sustaining injury due to alcohol-related incidents (NIAAA, 2013). Students enrolled in a Psychopharmacology course engaged in action projects (community outreach) focused on alcohol abuse on our campus. Research has indicated that these types of projects can increase student engagement in course material and foster important skills, including working with peers and developing involvement in one's community. This paper describes the structure and requirements of five student outreach projects and the final projects designed by the students, summarizes the grading and assessment of the projects, and discusses the rewards and challenges of incorporating such projects into a course. PMID- 27385922 TI - Using Cultured Mammalian Neurons to Study Cellular Processes and Neurodegeneration: A Suite of Undergraduate Lab Exercises. AB - Cell culture is a powerful tool for exploring cellular function. Culturing primary neurons has revealed how neurons communicate in learning and memory (Kandel, 2006) and provided insights into the mechanisms of neurodegenerative diseases such as Parkinson's and Alzheimer's disease (Alberio et al., 2012; Trinchese, et al., 2004). Here we describe a series of four modular laboratory exercises to integrate this neuroscience technique in undergraduate teaching laboratories. First, we describe the modular approach. Then we provide educators with simple techniques for culturing rat primary neurons, performing immunohistochemistry to label cellular components, and illustrating neurodegeneration caused by reactive oxygen species. We describe teaching exercises that culminate in student-generated research projects. Finally, we describe potential barriers students may face when integrating modern cell culture experiments into teaching laboratories. PMID- 27385924 TI - A Quantitative Examination of Undergraduate Neuroscience Majors Applying and Matriculating to Osteopathic Medical School. AB - Undergraduates choose to become neuroscience majors for a number of reasons including future career goals. Faculty and administration of undergraduate neuroscience programs understand that many neuroscience majors have aspirations of applying and matriculating to medical school (Prichard, 2015); however a quantitative understanding of this particular student population remains unknown, especially in the context of the national growth in undergraduate neuroscience education (Ramos et al., 2011). In the present report, we use medical school application data to establish a novel quantitative understanding of the number of neuroscience majors that apply and matriculate to osteopathic medical school. Our data indicate that a substantial number of neuroscience majors do indeed apply and matriculate to medical school compared to other majors in the life sciences, math and physical sciences, and humanities. These data are relevant to faculty and administration of undergraduate neuroscience programs and suggest that when programmatic, curricular, and training decisions are made, they should be made in the context of the diverse motivations and professional goals of neuroscience majors including careers in medicine. Finally, our novel quantitative approach of determining student motivation and professional goals based on application/matriculation data, can complement traditional methods such as surveys and questionnaires and can be used to determine the extent to which neuroscience majors apply to other professional and graduate degree programs. PMID- 27385925 TI - Incorporating an ERP Project into Undergraduate Instruction. AB - Electroencephalogram (EEG) is a relatively non-invasive, simple technique, and recent advances in open source analysis tools make it feasible to implement EEG as a component in undergraduate neuroscience curriculum. We have successfully led students to design novel experiments, record EEG data, and analyze event-related potentials (ERPs) during a one-semester laboratory course for undergraduates in cognitive neuroscience. First, students learned how to set up an EEG recording and completed an analysis tutorial. Students then learned how to set up a novel EEG experiment; briefly, they formed groups of four and designed an EEG experiment on a topic of their choice. Over the course of two weeks students collected behavioral and EEG data. Each group then analyzed their behavioral and ERP data and presented their results both as a presentation and as a final paper. Upon completion of the group project students reported a deeper understanding of cognitive neuroscience methods and a greater appreciation for the strengths and weaknesses of the EEG technique. Although recent advances in open source software made this project possible, it also required access to EEG recording equipment and proprietary software. Future efforts should be directed at making publicly available datasets to learn ERP analysis techniques and making publicly available EEG recording and analysis software to increase the accessibility of hands-on research experience in undergraduate cognitive neuroscience laboratory courses. PMID- 27385926 TI - The BRAIN Initiative Provides a Unifying Context for Integrating Core STEM Competencies into a Neurobiology Course. AB - The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative introduced by the Obama Administration in 2013 presents a context for integrating many STEM competencies into undergraduate neuroscience coursework. The BRAIN Initiative core principles overlap with core STEM competencies identified by the AAAS Vision and Change report and other entities. This neurobiology course utilizes the BRAIN Initiative to serve as the unifying theme that facilitates a primary emphasis on student competencies such as scientific process, scientific communication, and societal relevance while teaching foundational neurobiological content such as brain anatomy, cellular neurophysiology, and activity modulation. Student feedback indicates that the BRAIN Initiative is an engaging and instructional context for this course. Course module organization, suitable BRAIN Initiative commentary literature, sample primary literature, and important assignments are presented. PMID- 27385927 TI - Nora's Medulla: A Problem-Based Learning Case for Neuroscience Fundamentals. AB - Students work through this Problem-Based Learning Case in order to discover how Nora ended up blue lipped and non-responsive. By exploring fundamental mechanisms of neuronal communication, students examine facts, research concepts, and propose hypotheses about how Nora's physiology was disrupted to cause her respiratory distress. The dramatic context supports student learning at many levels - from systems neurophysiology to synaptic pharmacology. The case as written is used in an undergraduate course for non-science majors, but because the case focuses on basic fundamental neuroscience concepts, the case could be easily used in high school or other undergraduate courses that cover basic neuroscience. PMID- 27385928 TI - Case Studies and Neuroscience Education: Tools for Effective Teaching. PMID- 27385929 TI - Career Advice: Finding a Job at a Predominantly Undergraduate Institution. AB - Seeking a teaching job at a predominantly undergraduate college or university can be a daunting proposition. Although reports from the Bureau of Labor Statistics suggest that the job market for teaching positions at postsecondary institutions will be healthy over the coming decade, competition for these positions will likely be intense. This essay explores the profiles of predominantly undergraduate institutions (PUIs), the nature of faculty positions at PUIs, the elements that make for a competitive job applicant, and strategies to consider during negotiations. Seeking a position at a PUI may be arduous at times, but the rewards reaped from a successful search for a PUI position are well worth the investment. PMID- 27385930 TI - Diversity is Inclusion. PMID- 27385931 TI - Teaching as THE Oldest Profession. PMID- 27385932 TI - Developing Science Communication in Africa: Undergraduate and Graduate Students should be Trained and Actively Involved in Outreach Activity Development and Implementation. AB - Despite recent improvements in scientific research output from Africa, public understanding of science in many parts of the continent remains low. Science communication there is faced with challenges such as (i) lack of interest among some scientists, (ii) low availability of training programs for scientists, (iii) low literacy rates among the public, and (iv) multiplicity of languages. To address these challenges, new ways of training and motivating scientists to dialogue with non-scientists are essential. Developing communication skills early in researchers' scientific career would be a good way to enhance their public engagement abilities. Therefore, a potentially effective means to develop science communication in Africa would be to actively involve trainee scientists (i.e., undergraduate and graduate students) in outreach activity development and delivery. These students are often enthusiastic about science, eager to develop their teaching and communication skills, and can be good mentors to younger students. Involving them in all aspects of outreach activity is, therefore, likely to be a productive implementation strategy. However, science communication training specifically for students and the involvement of these students in outreach activity design and delivery are lacking in Africa. Here, we argue that improving the training and involvement of budding scientists in science communication activities would be a good way to bridge the wide gap between scientists and the African public. PMID- 27385933 TI - Nu Rho Psi, The National Honor Society in Neuroscience: A decade of progress. AB - Nu Rho Psi, the National Honor Society in Neuroscience, celebrates its 10th anniversary by reflecting back upon a decade's worth of growth, successes, and accomplishments of its membership. Fundamentally, Nu Rho Psi seeks to engage the nation's best and brightest science students early in their educational pursuits and steer them towards future careers in neuroscience, thereby driving higher quality neuroscience education and research at all levels. This article details the history of Nu Rho Psi since its founding by the Faculty for Undergraduate Neuroscience (FUN) and reviews the current programs, benefits, and future initiatives of the Society. We make the case that Nu Rho Psi has enhanced the opportunities for undergraduate students of neuroscience and created a new culture among this vital cohort of budding scientists, reminiscent of the substantial network of faculty educators and departments of neuroscience established by FUN. PMID- 27385934 TI - Running Wheel for Earthworms. AB - We describe the construction and use of a running wheel responsive to the movement of the earthworm. The wheel employs readily available, inexpensive components and is easily constructed. Movement of the wheel can be monitored visually or via standard behavioral laboratory computer interfaces. Examples of data are presented, and possibilities for use in the teaching classroom are discussed. PMID- 27385935 TI - The Stakes Are Higher Than Ever for Delivery of Quality Care. PMID- 27385936 TI - Blunt Force May be an Effective Treatment for Ganglion Cysts. AB - BACKGROUND: Ganglion cysts are the most common soft tissue tumors of the hand and wrist. There is currently no data available for the recurrence or complication rate of patients that self treat ganglion cysts by using an extrinsic force. Despite this absence of evidence, patients are still using this mode of treatment. QUESTIONS/PURPOSES: The purpose of the study is to evaluate the efficacy of blunt force as a treatment modality for disrupting ganglion cysts. METHODS: We analyzed videos of patients attempting to disrupt their ganglion cysts of the wrist by blunt force on Youtube.com and surveyed them anonymously. Candidates were contacted through YouTube's email server and given a link to an online questionnaire. RESULTS: Two hundred fourteen individuals were reviewed with a total of 1,008,913 views. Eighty three percent of videos were effective in treating the cyst. All 38 individuals that responded to the survey reported that the blunt force was effective in immediate elimination of the cyst in an average of 1.6 attempts (range 1-5). A majority (N = 21, 55%) reported no recurrence since the initial disruption of the cyst at a follow-up of 24 months. CONCLUSIONS: YouTube.com was found to be an effective outlet to study a treatment modality that would otherwise be limited by practical considerations. The study showed that a subset of patients is utilizing blunt force trauma to successfully treat wrist ganglion cysts. PMID- 27385937 TI - Outcomes of Proximal Humerus Fracture Open Reduction Internal Fixation with Concomitant Ipsilateral Shoulder Girdle Injuries: a Case Control Study. AB - BACKGROUND: Proximal humerus fractures treated in the face of ipsilateral injuries to the shoulder girdle may be predisposed to worse clinical outcomes. QUESTIONS/PURPOSES: The purpose of this investigation was to examine outcomes of proximal humerus fractures treated with open reduction internal fixation (ORIF) using an endosteal augment in the presence of a concomitant shoulder girdle injury in comparison to isolated proximal humerus fractures treated with ORIF and endosteal augment. METHODS: A prospective database was used to identify proximal humerus fractures with ipsilateral shoulder girdle injuries (glenohumeral and acromioclavicular dislocation, fractures of the acromion, clavicle, scapula, or humeral diaphysis). These were compared to isolated proximal humerus fractures treated in the same fashion (ORIF with endosteal augment). Minimum of 1 year follow-up was required for inclusion. Outcomes assessed included range of motion (ROM), development of avascular necrosis (AVN), hardware-related complications, reoperation, and subjective outcome assessments including the Disabilities of Arm Shoulder and Hand questionnaire (DASH), Constant score, UCLA rating scale, and the Short Form-36 (SF-36). RESULTS: Fifteen ipsilateral injuries were seen in 14 patients. Seventy-seven isolated proximal humerus fractures were available for comparison. The ipsilateral injury group had significantly worse forward flexion (141 vs 156 degrees , p = 0.02), external rotation (56 vs 64 degrees , p = 0.03), higher rates of avascular necrosis (4 of 14, 28.6% vs 1 of 77, 1.3%, p = 0.002), and inferior SF-36 physical health scores (48.5 vs 63.5; p = .04). Despite these differences, no significant differences were seen with hardware-related complications or DASH, Constant score, or UCLA rating scale results. No patients required secondary reconstructive procedures. CONCLUSION: Despite a statistically higher rate of AVN and decreased ROM, patient-based outcomes of proximal humerus fractures with ipsilateral shoulder injuries approached those seen in isolated proximal humerus fractures. This suggests that these injuries can achieve similarly good clinical results provided any associated shoulder pathology is identified and treated appropriately. PMID- 27385938 TI - Fast-Pitch Softball Pitchers Experience a Significant Increase in Pain and Fatigue During a Single High School Season. AB - BACKGROUND: Fast-pitch softball is one of the fastest growing sports, but there is little research regarding pitcher fatigue. Currently, there are no pitch limits or game counts. QUESTIONS/PURPOSES: To study the effect of fatigue on youth fast-pitch softball pitchers during a high school season, we hypothesized increased games pitched during the season would correlate with increased player reported pain and fatigue and decreased with upper extremity strength and range of motion (ROM). METHODS: This prospective cross-sectional study evaluated pre- and postgame shoulder and elbow strength, ROM, pain, and fatigue in 17 high school fast-pitch softball pitchers. These measures were recorded at two games, one at the beginning and one at the end of the season. Pitch count and number of games pitched during the season were recorded. We compared pre- and postgame measurements and measurements made at the beginning and end of the season. RESULTS: Supraspinatus, forward flexion strength, and external rotation strength in abduction decreased significantly postgame compared to pregame. Pregame pain and fatigue increased with a greater number of games pitched during the season. Forward flexion, supraspinatus, and external rotation strength decreased with increasing number of games pitched during the season. CONCLUSIONS: Fast-pitch softball pitchers experience increased pain and fatigue during a single game and over the entire season. The increase in fatigue may predispose the player to injury. Further studies are needed to understand the relationship of pain and fatigue with predisposition to injury. PMID- 27385939 TI - Evaluating the Diagnostic Yield of Computed Tomography-Guided Aspirations in Suspected Post-operative Spine Infections. AB - BACKGROUND: Early detection of surgical site infection (SSI) following spinal surgery would allow for prompt treatment and would improve overall outcome, yet early diagnosis is a challenge. Computed tomography (CT) guided aspiration of fluid collections may aid in diagnosis, as its diagnostic utility has previously been demonstrated in the setting of hip SSI, knee SSI, and spontaneous diskitis. There is no literature on its use in post-operative spinal SSIs. QUESTIONS/PURPOSES: The current study aims to (1) determine the diagnostic value of CT-guided aspiration in evaluating suspected SSI; (2) identify the characteristics of the clinical presentation that are predictive of SSI; and (3) identify characteristics of the hematologic workup that are predictive of SSI. METHODS: Thirty patients who underwent CT-guided aspiration of paraspinal post operative fluid collections and culture of aspirate fluid over the 6-year period from 2006 to 2011 were retrospectively reviewed. Aspirate fluid culture results were compared to intraoperative cultures, which were used as the "gold standard" for diagnosing SSI. The diagnostic value was evaluated by determining the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of aspirate fluid cultures. Clinical presentation, patient demographics, comorbidities, and laboratory values were reviewed for association with infection risk. RESULTS: Eleven of thirty patients undergoing CT-guided aspiration were subsequently confirmed to have SSI through positive cultures. Wound drainage, wound erythema, elevated ESR, and cloudiness of aspirate fluid were associated with SSI. The sensitivity and specificity of aspirate cultures were 36.4 and 89.5%, respectively, and the respective positive predictive value (PPV) and negative predictive value (NPV) were 66.7 and 70.8%. CONCLUSIONS: Cloudy aspirate fluid was highly suggestive of infection, while wound erythema, drainage, and elevated ESR were also suggestive of SSI. CT-guided aspirations are a useful adjunct tool in evaluating for SSI but further studies are necessary before it can be considered a stand-alone diagnostic procedure. PMID- 27385940 TI - The Effect of Regional Analgesia on Vascular Tone in Hip Arthroplasty Patients. AB - BACKGROUND: While it is assumed that neuraxial analgesia and pain management may beneficially influence perioperative hemodynamics, few studies provided data quantifying such effects and none have assessed the potential contribution of the addition of a nerve block. QUESTIONS/PURPOSES: This clinical trial compared the visual analog scale (VAS) scores and measurement of arterial tone using augmentation index of patients who received combined spinal-epidural (CSE) only to patients who received both CSE and lumbar plexus block. METHODS: After obtaining written consent, 92 patients undergoing total hip arthroplasty were randomized to receive either CSE or CSE with lumbar plexus block (LPB). Perioperative pain and arterial tone were measured using VAS scores and augmentation index (AI) respectively, at baseline and at various times postoperatively. RESULTS: After the exclusion of 2 patients, 44 patients received CSE alone and 46 patients received CSE and LPB. Patient demographics and perioperative characteristics were similar in both groups. AI continuously decreased after placement of a CSE with or without LBP, beyond full resolution of neuraxial and peripheral blockade. Although the LPB group demonstrated a statistically significant reduction of VAS pain scores in the postanesthesia care unit (PACU; P < 0.05), overall, the addition of a LPB did not significantly reduce the AI when compared to the control group. CONCLUSION: The addition of a LPB provided better pain control in the PACU but did not reduce the AI, compared to the control group. We conclude that the addition of a LPB may have limited ability to affect arterial tone in the presence of a continuous infusion of epidural analgesics. In summary, the addition of a LPB in patients undergoing total hip arthroplasty is clinically effective and provided better pain control, especially in the immediate postoperative period. The continuous decrease on the AI in both groups beyond the full resolution of the neuroaxial and LPB will require further studies. PMID- 27385941 TI - Duplex Ultrasonography Has Limited Utility in Detection of Postoperative DVT After Primary Total Joint Arthroplasty. AB - BACKGROUND: Duplex ultrasound is routinely used to evaluate suspected deep venous thrombosis after total joint arthroplasty. When there is a clinical suspicion for a pulmonary embolism, a chest angiogram (chest CTA) is concomitantly obtained. QUESTIONS/PURPOSES: Two questions were addressed: First, for the population of patients who receive duplex ultrasound after total joint arthroplasty, what is the rate of positive results? Second, for these patients, how many of these also undergo chest CTA for clinical suspicion of pulmonary embolus and how many of these tests are positive? Furthermore, what is the correlation between duplex ultrasound results and chest CTA results? METHODS: A retrospective chart review was conducted of total joint replacement patients in 2011 at a single institution. Inclusion criteria were adult patients who underwent a postoperative duplex ultrasonography for clinical suspicion of deep venous thrombosis (DVT). Demographic data, result of duplex scan, clinical indications for obtaining the duplex scan, and DVT prophylaxis used were recorded. Additionally, if a chest CTA was obtained for clinical suspicion for pulmonary embolus, results and clinical indication for obtaining the test were recorded. The rate of positive results for duplex ultrasonography and chest CTA was computed and correlated based on clinical indications. RESULTS: Two hundred ninety-five patients underwent duplex ultrasonography of which only 0.7% were positive for a DVT. One hundred three patients underwent a chest CTA for clinical suspicion of a pulmonary embolism (PE) of which 26 revealed a pulmonary embolus, none of which had a positive duplex ultrasound. CONCLUSION: Postoperative duplex scans have a low rate of positive results. A substantial number of patients with negative duplex results subsequently underwent chest CTA for clinical suspicion for which a pulmonary embolus was found, presumably resulting from a DVT despite negative duplex ultrasound result. A negative duplex ultrasonography should not rule out the presence of a DVT which can embolize to the lungs and thus should not preclude further workup when clinical suspicion exists for a pulmonary embolus. PMID- 27385942 TI - The Efficacy of Bisphosphonates with Core Decompression and Mesenchymal Stem Cells Compared with Bisphosphonates Alone in the Treatment of Osteonecrosis of the Hip: a Retrospective Study. AB - INTRODUCTION: Osteonecrosis of the femoral head (ONFH) is a devastating disease with complete collapse of the femoral head often reported in greater than 70% of patients within 3 to 4 years of diagnosis. Early intervention prior to collapse may improve the chance of success of joint preserving procedures. QUESTIONS/PURPOSES: The purpose of this study was to evaluate whether core decompression with mesenchymal stem cells combined with bisphosphonate therapy can improve the clinical outcomes and reduce the risk of hip replacement when compared to treatment with bisphosphonate therapy alone. METHODS: Between 2006 and 2014, 84 consecutive patients who were diagnosed with ONFH were identified from our institution's registry. Of these 84 patients, 49 patients (62 hips), fit inclusion/exclusion criteria. Twenty-nine patients (40 hips) were treated with bisphosphonate therapy only. Twenty patients (20 hips) were treated with bisphosphonates, core decompression, and mesenchymal stem cells. Functional outcomes were assessed using the Modified Harris Hip Score (MHHS), the visual analog score (VAS), and evaluation of support system. Clinical failure was defined as deterioration of the MHHS/VAS scores and support system used severe enough to require THR. Radiologic outcome measures included the XR and MR imaging staging of the hip. Survival analysis was performed with total hip replacement as the end point failure. Collapse was defined as progression from Ficat stage I or II to stage III and from Steinberg I, II, III to IV, V, VI. RESULTS: Failure requiring THR occurred in 21/40 (52.5%) of bisphosphonates (BP)-treated hips at a mean follow-up of 25.3 +/- 11.5 months and 5/22 (22.73%) of BP + CD + MSC-treated hips at a mean follow-up of 22.7 +/- 19.5 months. The median (Q1, Q3) time to collapse was 24.9 (7.4, 33.0) months in BP-treated hips and 27.3 (27.3) months in BP + CD + MSC-treated hips. There was no evidence of a difference in functional outcomes between the two treatment groups. After adjusting for baseline Ficat stage, age, and sex, an unreplaced hip treated with BP + CD + MSC had 0.42 (95% CI 0.11, 1.57) times the risk of being replaced in the next moment compared to an unreplaced hip treated with bisphosphonates only (P = 0.196). CONCLUSION: Our results demonstrate that treatment with BP alone or BP + CD + MSC can postpone the need for total hip arthroplasty (THA) in the first 24 months in patients with ONFH compared to previously reported data, but there is no statistically significant difference between the two treatment groups. Combination therapy of BP + CD + MSC may be more effective in delaying the progression of collapse in early stage ONFH. Future prospective studies are warranted to determine the efficacy of these treatment strategies in the long term. PMID- 27385943 TI - Is There a Threshold for Stiffness Complaints Following TKA on the WOMAC Stiffness Subscale? AB - BACKGROUND: Stiffness complaints after total knee arthroplasty (TKA) are frequent, yet poorly understood and can be challenging for surgeons to address. The WOMAC stiffness subscale is a widely used measure of stiffness and can serve as a simple screening tool for complaints. QUESTIONS/PURPOSES: We aimed to identify a threshold for stiffness complaints on the WOMAC stiffness subscale and investigate its overlap with range of motion (ROM) in TKA patients. METHODS: TKA patients were enrolled preoperatively and followed for 6 months. At follow-up, patients reported their ROM, completed the WOMAC stiffness subscale (range 1-8 with 8 continuous stiffness) and indicated whether they experienced more stiffness than expected. To identify a threshold for complaints, we compared patients' WOMAC stiffness scores to when they experienced more stiffness than expected, visually, and statistically. We also mapped ROM limitations at 6 months to WOMAC stiffness scores. Finally, we determined if baseline characteristics were associated with stiffness complaints. RESULTS: Two hundred and forty-six TKA patients were enrolled preoperatively with 82% follow-up rate at 6 months. Our results showed that patients with a WOMAC stiffness score = 3+ were significantly more likely to experience more stiffness than expected. Patients reporting full ROM (54%) reported a wide range of WOMAC stiffness subscale scores (1-6). Baseline WOMAC pain and function scores were the only factors associated with stiffness complaints. CONCLUSIONS: ROM is a poor surrogate of patient-reported stiffness, and the patients' perception of "stiffness" is clearly more complex than just ROM. We identified a WOMAC threshold that could potentially easily serve this purpose. PMID- 27385944 TI - Low Levels of Vitamin D have a Deleterious Effect on the Articular Cartilage in a Rat Model. AB - BACKGROUND: Vitamin D appears to play an important role in bone and cartilage metabolism since its receptors are widely found in human articular chondrocytes. Thus, effects of variation of vitamin D may directly impact cartilage and bone biology. QUESTIONS/PURPOSES: The aims of this study are to compare (1) articular cartilage structure and composition and (2) trabecular and cortical bone microstructure in rats with normal versus insufficient vitamin D levels. METHODS: Twenty-five mature, male Sprague-Dawley rats were allocated to two groups: (1) control arm (vitamin D replete-12 rats) and (2) an experimental arm (vitamin D deficient-13 rats). Vitamin D deficiency was induced using a vitamin D-deficient diet and UV light restriction. Rats were sacrificed after 4 weeks vitamin D deficiency was confirmed. The right knee was harvested for analysis of both the medial (MFC) and lateral femoral condyles (LFC). A region of interest was established on both condyles to correlate subchondral bone architecture and the overlying cartilage. Histological analysis was performed and graded using the modified Mankin score. Subchondral and cortical bony architecture was evaluated with micro-CT. RESULTS: After 4 weeks, the vitamin D-deficient group had statistically significant changes in cartilage structure in both the MFC and LFC [1.55 +/- 0.6 vs. 4.23 +/- 4.1 (p = 0.035) and 1.55 +/- 0.6 vs. 3.53 +/- 2.4 (p = 0.009), respectively]. Micro-CT analysis revealed no correlation between subchondral bone values and the overlying cartilage Mankin score (p = 0.460). No significant difference was evident between the subchondral bone of the control and study group. CONCLUSIONS: Low levels of vitamin D have a deleterious effect on the cartilage. Given the high prevalence of vitamin D deficiency in the general population, these findings raise important questions about the potential role of vitamin D in articular cartilage health. PMID- 27385945 TI - Fringe Benefits Among US Orthopedic Residency Programs Vary Considerably: a National Survey. AB - BACKGROUND: Residency programs compete to attract applicants based on numerous factors. Previous research has suggested that medical students consider quality of life among the most important factors in selecting a program. One aspect of workplace quality of life is the cadre of non-monetary benefits offered to employees. However, with federal funding for graduate medical education (GME) under consideration for spending cuts, the source and continuation of such benefits may be in question. QUESTIONS/PURPOSES: This study aimed to determine the level and variability of benefits beyond standard salary and insurance options available to trainees at US orthopedic residency programs and to assess the source of funding for those benefits. METHODS: A 26-question survey investigating various benefits and funding sources was circulated by email to all ACGME-accredited orthopedic residency programs. RESULTS: The survey was sent to 153 programs and 69 responded (45%). The majority offers their residents discretionary funds (77%) and conference funding (96%), most of which comes from the department, followed by the hospital or GME funding. Forty-one percent of respondents permit their residents to moonlight. The majority of respondents provide meal stipends (93%), free parking (71%), gym benefits (63%), surgical loupes (53%), and maternity/paternity leave beyond vacation time (55%). No statistically significant differences were found among top ranked residencies, top ranked orthopedic hospitals, or academic centers compared to their counterparts. CONCLUSION: While some benefits are commonly offered, there is great variation in the availability and level of others. However, these differences were independent of program and hospital reputation as well as academic center status. Departments currently bear a substantial amount of the cost of these benefits internally. PMID- 27385946 TI - Direct Repair of the Superior Band of Bigelow's Ligament After Hip Arthroplasty: a Surgical Technique. AB - BACKGROUND: The posterolateral approach is one of the most common approaches used during hip arthroplasty. A posterior soft tissue repair is necessary to limit the risk of postoperative dislocation. For a trapezoidal capsulotomy, the proximal limb divides the superior band of the iliofemoral ligament (Bigelow's ligament). A transosseous repair frequently leaves a defect in this region, which may elevate the risk for dislocation. The purpose of this article is to describe a simple, rational technique for reinforcing the posterior capsular repair. DESCRIPTION OF TECHNIQUE: A meticulous exposure of the hip capsule is performed during the posterolateral surgical approach. A trapezoidal capsulotomy is performed. After implantation of the arthroplasty implants, retractors are placed to expose the superior capsule. Prior to transosseous repair of the capsule and short external rotator tendons, the proximal limb of the capsulotomy is reapproximated anatomically and repaired with non-absorbable sutures. If anatomical repair is not possible, leg length and femoral offset should be reassessed carefully. DISCUSSION: The described modification may further minimize the risk of dislocation following hip arthroplasty, as the superior band of Bigelow's ligament is an additional checkrein to internal and external rotation. This repair provides a secondary intraoperative assessment of leg length and femoral offset to ensure proper biomechanical reconstruction of the hip joint. It is the authors' preferred technique of all hip hemiarthroplasties and total hip arthroplasties, whenever possible. PMID- 27385947 TI - A Systematic Review of Preoperative Fatty Infiltration and Rotator Cuff Outcomes. AB - BACKGROUND: Fatty infiltration (FI) of the muscle as graded by the Goutallier classification (GC) is a well-known sequela following rotator cuff injury. The degree to which this predicts the success of rotator cuff repair is unknown. QUESTIONS/PURPOSES: We conducted a systematic review to address the following questions: (1) Does the grade of FI of the rotator cuff muscles present preoperatively predict retear rates postoperatively? (2) Are amounts of preoperative FI predictive of functional outcomes following repair? METHODS: Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Central Register of Controlled Trials online databases were searched for all literature published between January 1966 and March 2015. Keywords were chosen to achieve a broad search category. All articles were reviewed by three of the authors, and those meeting the study inclusion criteria were selected for data abstraction. RESULTS: The systematic literature review yielded 11 studies reporting on a total of 925 shoulders. Rotator cuffs with moderate or significant FI preoperatively (grades 2-4) had a significantly higher retear rate than those with no or minimal FI (grades 0-1) (59 vs. 25%, p = 0.045). Four studies reported postoperative Constant scores and preoperative GC scores. One study found that lower GC scores were associated with higher Constant scores postoperatively, one found no association, and the data was inconclusive in the other two. CONCLUSIONS: While lower preoperative GC scores are associated with lower rates of rotator cuff retear following repair, there is insufficient data to make conclusions on the effects of FI on functional outcomes following repair. PMID- 27385948 TI - Total Hip Arthroplasty in a Patient with Multicentric Carpotarsal Osteolysis: a Case Report. PMID- 27385949 TI - Successful Immediate Re-implantation of an Extruded Femoral Segment: a Case Report. PMID- 27385951 TI - Diagnosing Septic Arthritis in the Synovial White Cell Count "Gray Zone". AB - Differentiating septic arthritis of the pediatric hip from other causes of hip pain and effusion continues to present a diagnostic challenge for the clinician. Although septic arthritis traditionally has been reported to have a synovial white blood cell count of 75,000 cells/mm3 or greater, lower counts can be seen in this condition. In cases where a synovial sample has been obtained and the cell count falls in the intermediate range between 25,000 and 75,000 cells/mm(3), it is unclear what proportion of these cases may be truly septic hips. In this evidence-based review, we examine Heyworth et al's study focusing on the predictive value of this intermediate white cell count range in a Lyme-endemic region. PMID- 27385950 TI - Thoracic Spine Degeneration Following Microlaminotomy for Spinal Cord Stimulator Placement and Subsequent Removal-a Case Report. PMID- 27385952 TI - New Joints, Same Old Weight: Weight Changes After Total Hip and Knee Arthroplasty. AB - Obesity is a well-known risk factor for postoperative complications following total joint arthroplasty. However, because the operation is often successful, orthopedic surgeons continue to operate on obese individuals, and many surgeons do so under the assumption that patients will lose weight after they are able to walk and exercise without pain. In this article, we review a recent study by Ast et al., who performed a retrospective review, using a single-center institutional registry, to determine (1) whether patients do actually lose weight after total hip and/or total knee arthroplasty, (2) whether there are predictors of postoperative weight change, and (3) whether postoperative weight changes affect patient-reported clinical outcomes. The principle conclusion was that most patients maintained their body mass index (BMI) after total hip and total knee arthroplasty (73 and 69%, respectively). However, patients undergoing total knee arthroplasty, patients who had a higher preoperative BMI, and female patients were more likely to lose weight postoperatively. When examined in the context of the current literature, this study provides valuable information for the preoperative counseling of total joint arthroplasty candidates, especially in the setting of obesity. PMID- 27385953 TI - Farewell, Sam Delgado. PMID- 27385955 TI - Beyond the joints in rheumatoid arthritis: Effects of adalimumab on hematologic and lipid indices. AB - Tumor necrosis factor alpha (TNFalpha) is a multifunctional cytokine which plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). Apart from its well recognized proinflammatory properties, it is known to interfere with lipid metabolism and erythropoiesis. We evaluated the effects of adalimumab on hematologic, lipid and inflammatory parameters using data from patients on adalimumab 40 mg fortnightly from 2 centers in Malaysia. Mean changes in laboratory values from baseline to Weeks 4, 12 and 24 were compared using paired T test and Wilcoxon signed-rank test. We studied 18 patients with RA who were on adalimumab 40 mg fortnightly. The inflammatory markers i.e. erythrocyte sedimentation rate and C reactive protein showed significant changes as early as at week 4 compared to baseline with p values of 0.003 and 0.005, respectively. From a baseline of high disease activity with a mean Disease Activity Score using 28 joint counts (DAS 28) of 5.3, there was a steady improvement in the disease activity and remission was achieved at week 24 with a DAS 28 of 2.4. The hemoglobin level improved at week 12 (p=0.013) and this was sustained till week 24. As opposed to previous studies, the LDL level significantly decreased at week 12 (p=0.015) and this change persisted till week 24 (p=0.001). The total cholesterol showed a similar pattern as the LDL. The pharmacodynamics of adalimumab therapy in rheumatoid arthritis extend beyond the joints with favorable effects on haemoglobin and lipid profile. PMID- 27385954 TI - Neuroprotective effect of nitric oxide donor isosorbide-dinitrate against oxidative stress induced by ethidium bromide in rat brain. AB - This study investigated the effect of systemic administration of isosorbide dinitrate (ISDN) on oxidative stress and brain monoamines in a toxic model of brain demyelination evoked by intracerebral injection (i.c.i) of ethidium bromide (10 ul of 0.1 %). Rats received saline (control) or ISDN at 5 or 10 mg/kg for 10 days prior to injection of ethidium bromide. Rats were euthanized one day later, and then the levels of reduced glutathione (GSH), lipid peroxidation (malondialdehyde; MDA), nitric oxide (nitrite/nitrate), acetylcholinesterase (AChE) activity, paraoxonase activity as well as monoamine levels (serotonin, dopamine and noradrenaline) were assessed in the brain cortex in different treatment groups. The i.c.i of ethidium bromide resulted in increased oxidative stress in the cortex one day after its injection; (i) MDA increased by 36.9 %; (ii) GSH decreased by 20.8 %, while (iii) nitric oxide increased by 60.3 %; (iv) AChE and paraoxonase activities in cortex decreased by 35.9 % and 29.4 %, respectively; (v) serotonin was significantly increased. In ethidium bromide treated rats, pretreatment with ISDN at 10 mg/kg decreased cortical MDA by 23.9 %. Reduced glutathione was increased by 25.1 % ISDN at 10 mg/kg, while nitric oxide showed a 32.8 and 41.7 % decrease after 5 and 10 mg/kg of ISDN, respectively. Acetylcholinesterase activity increased by 24.3 % by 10 mg/kg of ISDN. Paraoxonase activity showed further decrease by 72.2 and 83.8 % after treatment with 5 and 10 mg/kg of ISDN, respectively. The administration of ISDN decreased the level of serotonin and noradrenaline compared with the ethidium bromide only treated group. Overall, the present findings suggest neuroprotective effect of ISDN against oxidative stress in this model of chemical demyelination. PMID- 27385956 TI - Effects of acute and chronic psychological stress on isolated islets' insulin release. AB - This study investigated the effects of acute and chronic psychological stress on glucose-stimulated insulin secretion from isolated pancreatic islets. Male Wistar rats were divided into two control and stressed groups; each further was allocated into fed and fasted groups. Stress was induced by communication box for one (acute), fifteen and thirty (chronic) days. After islet isolation, their number, size and insulin output were assessed. Plasma corticosterone level was determined. In fasted animals, acute stress increased basal and post stress plasma corticosterone level, while 30 days stress decreased it compared to day 1. In fed rats, acute stress increased only post stress plasma corticosterone concentration, however, after 15 days stress, it was decreased compared to day 1. Acute stress did not change insulin output; however, the insulin output was higher in the fed acutely stressed rats at 8.3 and 16.7 mM glucose than fasted ones. Chronic stress increased insulin output on day 15 in the fasted animals but decreased it on day 30 in the fed animals at 8.3 and 16.7 mM glucose. In the fasted control rats insulin output was lower than fed ones. In the chronic stressed rats insulin output at 8.3 and 16.7 mM glucose was higher in the fasted than fed rats. The number of islets increased in the fasted rats following 15 days stress. This study indicated that the response of the isolated islets from acute and chronically stressed rats are different and depends on the feeding status. PMID- 27385957 TI - The role of protein kinase C in ischemic tolerance induced by hyperoxia in rats with stroke. AB - Recent studies suggest that normobaric hyperoxia (HO) protects the rat brain from ischemia reperfusion (IR) injury. Protein kinase C (PKC) is a key signaling molecule involved in protection against IR injury but its role in protective effect of HO in brain injury in unknown. In this study we attempted to see if PKC is involved in the effect of HO. Rats were divided into four main experimental groups. The first two were exposed to 95 % oxygen (HO) in a chamber 4 h/day for 6 consecutive days. Each of these groups had a control group exposed to 21 % oxygen. To investigate the role of PKC during HO, chelerythrin chloride (CHEL, 1 mg/kg/day), a PKC inhibitor, or its vehicle was given to animals for 6 days. After 24 h, the rats were subjected to 60 min of right middle cerebral artery occlusion (MCAO). After 24 h reperfusion neurological deficit scores, infarct volume, brain edema and blood-brain Barrier (BBB) permeability were assessed. HO decreased the infarct volume and brain edema in comparison with controls. PKC inhibition was associated with a significant increase in infarct size in both HO and control animals. PKC inhibition was unable to change brain edema in the experimental groups. Both HO and PKC inhibition reduced the BBB permeability within 24 h post occlusion of middle cerebral artery. Although both HO and PKC inhibition were associated with inhibition of BBB permeability during ischemic brain injury in rats, the neuroprotective effect of HO was independent of PKC in the MCAO model. PMID- 27385958 TI - Biological activities of extracts from cultivated Granadilla Passiflora alata. AB - Research conducted in this study showed the influence of ethanol, acetone and ethyl acetate extracts of the outgrowth of cultivated Passiflora alata on microorganisms, as well as the antioxidant activity and the concentrations of total phenols, flavonoids and tannins. In vitro antimicrobial activities of extracts were studied on 27 species of microorganisms, of which 17 species of bacteria and 10 species of fungi. The strongest antimicrobial activity was detected on G+ bacteria while the activities on other species were moderate. Ethyl acetate extract showed the strongest effect. The concentrations of total phenols were examined by using Folin-Ciocalteu reagent and the obtained values ranged from 14.04 to 34.22 mg GA/g. By using aluminium chloride method, the concentrations of flavonoids were obtained and the values ranged from 33.19 to 62.30 mg RU/g. In determining the amount of tannins we used the method with buthanol-HCl reagent and the obtained value was 5.1 % of dry matter. The efficiency of antioxidation, which we identified through the reduction of DPPH, was in the range from 808.69 to 1107.79 ug/ml for a particular IC50, and AAI values were between 0.07 and 0.10. The best parameters were shown by ethanol extract. All data were statistically analyzed. Overall, extracts showed potential for further investigation and use. PMID- 27385959 TI - Changes in apoptotic factors in hypothalamus and hippocampus after acute and subchronic stress induction during conditioned place preference paradigm. AB - The hypothalamus (HYP) and hippocampus (HIP) are important regions involved in stress responses. These areas are also associated with reward processing. In this study, the effects of acute and subchronic stress on the changes in apoptotic factors (Bax/Bcl-2 ratio, caspase-3 activation and PARP degradation) in the HYP and HIP during conditioned place preference (CPP) paradigm were evaluated. Male Wistar rats were divided into two saline- and morphine-treated supergroups. Each supergroup contained control, acute stress (AS) and subchronic stress (SS) groups. In all groups, CPP paradigm was done and thereinafter alterations of apoptotic factors were measured by western blot. The results revealed that in the HYP, all mentioned factors increased significantly in saline- or morphine-treated animals during AS and SS. On the other hand, in the HIP, Bax/Bcl-2 ratio in saline-treated animals increased significantly during AS and SS, while in morphine-treated animals this ratio did not have any significant alteration during AS and was decreased during SS compared with morphine-control group. Caspase-3 and PARP increased during AS and SS in saline- or morphine-treated animals. For example, caspase-3 increased during AS and SS in morphine-treated animals by 2.4 folds and PARP (89 KDa) increased by 3.1 and 3.5 folds, respectively. Interestingly, the increase of apoptotic factors in morphine treated animals was more considerable than that of saline-treated animals. These results strongly implied that AS and SS trigger apoptotic events in the HYP and HIP of saline- and/or morphine-treated animals as well as morphine reinforces the effect of stress on the induction of apoptosis. PMID- 27385960 TI - The Growing Complexity of the Monosomy 1p36 Syndrome. PMID- 27385963 TI - RASopathies: Presentation at the Genome, Interactome, and Phenome Levels. AB - Clinical symptoms often reflect molecular correlations between mutated proteins. Alignment between interactome and phenome levels reveals new disease genes and connections between previously unrelated diseases. Despite a great potential for novel discoveries, this approach is still rarely used in genomics. In the present study, we analyzed the data of 6 syndromes belonging to the RASopathy class of disorders (RASopathies) and presented them as a model to study associations between genome, interactome, and phenome levels. Causative genes and clinical symptoms were collected from OMIM and NCBI GeneReviews databases for 6 syndromes: Noonan, Noonan syndrome with multiple lentigines, neurofibromatosis type 1, cardiofaciocutaneous, and Legius and Costello syndrome. The STRING tool was used for the identification of protein interactions. Six RASopathy syndromes were found to be associated with 12 causative genes. We constructed an interactome of RASopathy proteins and their neighbors and developed a database of 328 clinical symptoms. The collected data was presented at genome, interactome, and phenome levels and as an integrated network of all 3 data types. The present study provides a baseline for future studies of associations between interactome and phenome in RASopathies and could serve as a novel approach to analyze phenotypically and genetically related diseases. PMID- 27385961 TI - Cytogenomic Aberrations in Congenital Cardiovascular Malformations. AB - Congenital cardiovascular malformations are the most common birth defects, with a complex multifactorial etiology. Genetic factors play an important role, illuminated by numerous cytogenetically visible abnormalities, as well as submicroscopic genomic imbalances affecting critical genomic regions in the affected individuals. Study of rare families with Mendelian forms, as well as emerging next-generation sequencing technologies have uncovered a multitude of genes relevant for human congenital cardiac diseases. It is clear that the complex embryology of human cardiac development, with an orchestrated interplay of transcription factors, chromatin regulators, and signal transduction pathway molecules can be easily perturbed by genomic imbalances affecting dosage sensitive regions. This review focuses on chromosomal abnormalities contributing to congenital heart diseases and underscores several genomic disorders linked to human cardiac malformations in the last few decades. PMID- 27385962 TI - Bardet-Biedl Syndrome. AB - Bardet-Biedl syndrome (BBS) is a rare autosomal recessive genetic disorder. It is characterized by heterogeneous clinical manifestations including primary features of the disease (rod-cone dystrophy, polydactyly, obesity, genital abnormalities, renal defects, and learning difficulties) and secondary BBS characteristics (developmental delay, speech deficit, brachydactyly or syndactyly, dental defects, ataxia or poor coordination, olfactory deficit, diabetes mellitus, congenital heart disease, etc.); most of these symptoms may not be present at birth but appear and progressively worsen during the first and second decades of life. At least 20 BBS genes have already been identified, and all of them are involved in primary cilia functioning. Genetic diagnosis of BBS is complicated due to lack of gene-specific disease symptoms; however, it is gradually becoming more accessible with the invention of multigene sequencing technologies. Clinical management of BBS is largely limited to a symptomatic treatment. Mouse experiments demonstrate that the most debilitating complication of BBS, blindness, can be rescued by topical gene therapy. There is a published case report describing the delay of BBS symptoms by nutritional compensation of the disease-related biochemical deficiencies. Progress in DNA testing technologies is likely to rapidly resolve all limitations in BBS diagnosis; however, much slower improvement is expected with regard to BBS treatment. PMID- 27385964 TI - Prolidase Deficiency in a Mexican-American Patient Identified by Array CGH Reveals a Novel and the Largest PEPD Gene Deletion. AB - Prolidase deficiency (PD) is a rare genetic disorder caused by mutations in the peptidase D (PEPD) gene, affecting collagen degradation. Features include lower extremity ulcers, facial dysmorphism, frequent respiratory infections, and intellectual disability, though there is significant intra- and interfamilial variability. Twenty-eight mutations have been previously reported, all either small deletions/duplications or point mutations discovered by enzyme or DNA assays. PD has been reported in patients of various ethnic backgrounds, but never in the Mexican-American population. We describe the first Mexican-American patient with PD, who presented with typical facial features, developmental delay, microcephaly, and xerosis. Chromosome microarray analysis (CMA) revealed a homozygous deletion in the region of 19q13.11, estimated to be between 124.79 and 195.72 kb in size, representing the largest PEPD gene deletion reported to date and the first discovered by CMA. PMID- 27385966 TI - A New Case of an Extremely Rare 3p21.31 Interstitial Deletion. AB - Interstitial 3p21.31 deletions have been very rarely reported. We describe a 7 year-old boy with global developmental delay, specific facial characteristics, hydronephrosis, and hypothyreosis with a de novo deletion of 3p21.31, encompassing 29 OMIM genes. Despite the wide use of microarrays, no similar case has been reported in the literature so far. Five overlapping cases are deposited in the DECIPHER database, 2 of which have significant overlapping chromosomal aberrations. They both share some phenotypic characteristics with our case, e.g. developmental delay, intellectual disability and facial dysmorphism (arched eyebrows, hypertelorism, low-set ears, and a large nose tip). In addition, loss of-function mutations in the SETD2 gene (OMIM 612778) of the deleted region have been described in 3 patients, presenting with some similar clinical features, namely overgrowth, intellectual disability, speech delay, hypotonia, autism, and epilepsy. Therefore, SETD2 may explain part of the phenotype in our case. We focused on 3 other genes in the deleted region, based on their known functions, namely CSPG5 (OMIM 606775), PTH1R (OMIM 168468) and SMARCC1 (OMIM 601732), and assessed their potentially important role in describing the patient's phenotype. Additional cases with haploinsufficiency of this region are needed to elucidate further genotype-phenotype correlations. PMID- 27385965 TI - Whole Exome Sequencing Reveals a Mutation in CRYBB2 in a Large Mexican Family with Autosomal Dominant Pulverulent Cataract. AB - Congenital cataract, an important cause of reversible blindness, is due to several causes including Mendelian inheritance. Thirty percent of cataracts are hereditary with participation of the gamma crystallin genes. Clinical and genetic heterogeneity is observed in patients with gene mutations and congenital cataract; about 40 genetic loci have been associated with hereditary cataract. In this study, we identified the underlying genetic cause of an autosomal dominant pulverulent cataract (ADPC) in a large Mexican family. Twenty-one affected patients and 20 healthy members of a family with ADPC were included. Genomic DNA was analyzed by whole exome sequencing in the proband, a normal daughter, and in an affected son, whereas DNA Sanger sequencing was performed in all members of the family. After the bioinformatics analysis, all samples were genotyped using Sanger sequencing to eliminate variants that do not cosegregate with the cataract. We observed a perfect cosegregation of a nonsense mutation c.475C>T (p.Q155*) in exon 6 of the CRYBB2 gene with ADPC. We calculated a logarithm of the odds score of 5.5. This mutation was not detected in healthy members of the family and in 100 normal controls. This is the first Mexican family with ADPC associated with a p.Q155* mutation. Interestingly, this specific mutation in the CRYBB2 gene seems to be exclusively associated with pulverulent/cerulean cataract (with some clinical variability) independent of the population's genetic background. PMID- 27385967 TI - Comparison of Serum Levels of Vitamin D and Inflammatory Markers Between Women With Gestational Diabetes Mellitus and Healthy Pregnant Control. AB - OBJECTIVE: Vitamin D appears to be involved in regulation of glycemic and inflammatory responses in gestational diabetes. The purpose of this study was to compare the serum levels of 25-hydroxyvitamin D (25(OH)D), inflammatory biomarkers and glycemic profile between gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT) pregnant women. MATERIALS AND METHODS: In this cross-sectional study, fasting serum levels of 25(OH)D, insulin, glucose, HOMA IR, hs-CRP and TNF-alpha were measured in 45 GDM and 45 NGT women at week 20-30 gestation whom referred to Reference Medical Laboratory of Ahvaz, Iran in 1394. RESULTS: Serum 25(OH)D levels were significantly lower (p = 0.003 ) in the GDM group compared to the NGT group which remained even after controlling for confounders. Insulin and TNF-alpha levels were not statistically different between groups (p > 0.05). However, in unadjusted model, HOMA-IR and hs-CRP were significantly different between groups that disappeared in adjusted model. In the GDM group, there was a negative significant correlation between 25 (OH) D and fasting blood sugar (p = 0.009) and pre pregnancy BMI (p < 0.001). Levels of 25(OH)D were also negatively correlated with pre pregnancy BMI (p < 0.001) and hs CRP levels (p = 0.003) in the NGT group. CONCLUSION: The lower level of vitamin D may be responsible for impairments of some glycemic and inflammatory markers in pregnant women. This is more important in overweight pregnant women. However, further studies with larger sample size are recommended in this regards. PMID- 27385968 TI - Validity and Reliability of Knowledge, Attitude and Behavior Assessment Tool Among Vulnerable Women Concerning Sexually Transmitted Diseases. AB - OBJECTIVE: The study aimed to design and evaluate the content and face validity, and reliability of knowledge, attitude, and behavior questionnaire on preventive behaviors among vulnerable women concerning sexually transmitted diseases (STDs). MATERIALS AND METHODS: This cross-sectional study was carried out in two phases of an action research. In the first phase, to explain STDs preventive domains, 20 semi- structured interviews were conducted with the vulnerable women, residing at women prison and women referred to counseling centers. After analyzing content of interviews, three domains were identified: improve their knowledge, modify their attitude and change their behaviors. In the second phase, the questionnaire was designed and tested in a pilot study. Then, its content validity was evaluated. Face validity and reliability of the questionnaire were assessed by test re- test method and Cronbach alpha respectively. RESULTS: Index of content validity in each three domain of the questionnaire (knowledge, attitude and behavior concerning STDs) was obtained over 0.6. Overall content validity index was 0.86 in all three domains of the questionnaire. The Cronbach's alpha as reliability of questionnaire was 0.80 for knowledge, 0.79 for attitude and 0.85 for behavior. CONCLUSION: The results showed that the designed questionnaire was a valid and reliable tool to measure knowledge, attitude and behavior of vulnerable women, predisposed to risk of STDs. PMID- 27385969 TI - Association of Smoking With Semen Quality and u-Calpain Level in Normospermia: A Case-Control Study. AB - OBJECTIVE: Calpains are a family of Ca(2+) dependent proteases. There is some evidence that calpains involved in fusion process that occurs between spermatozoa and the oocyte. The current study aimed to investigate the association of smoking with semen quality and u-calpain level. MATERIALS AND METHODS: This case-control study was conducted on 117 normospermia males between June 2013 and march 2014 in Jahad Laboratory in ahvaz, Iran. The semen samples were collected from male smokers (n = 50) and non-smokers (n = 67). We divided these participants as light, moderate, or heavy smokers based on their cigarettes per day (CPD). ELISA assays were used to measure u-calpain concentration. All semen samples were analyzed according to World Health Organization guidelines. RESULTS: The analysis of semen showed the volume, concentration, motility and morphology of semen were significantly lower among the smoker men than the non-smoker men. Also this significant difference was observed based on the number (light, moderate and heavy smokers) and duration (short term and long term smoker) of smoking. Although, showed no significant difference between u-calpain of smoker men and non-smoker men. CPD showed negatively correlation with semen volume, concentration, motility and morphology of sperm. CONCLUSION: Sperm quality was negatively correlated with CPD and duration of smoking. However, there is no significant correlation between smoking and u-calpain concentration. PMID- 27385970 TI - Comparison of the Effects of Lidocaine Prilocaine Cream (EMLA) and Lidocaine Injection on Reduction of Perineal Pain During Perineum Repair in Normal Vaginal Delivery. AB - OBJECTIVE: To compare the efficacy of EMLA cream and lidocaine injection to reduce pain during episiotomy repair. MATERIALS AND METHODS: A total of 46 primiparous women with normal pregnancy who referred for normal vaginal delivery and needed episiotomy repair were selected and randomly divided into two groups. For EMLA group, one hour before the estimated time of delivery, 5g of EMLA cream was applied to perinealmediolateral incision, and after the delivery of the fetus and placenta, again 5g of EMLA cream was applied to healthy skin around the episiotomy for repair. In the other group, lidocaine 2% was used before episiotomy and for its repair, too. RESULTS: Only 8 people (19%) were in need of further analgesia. The mean +/- SD of pain during repair of episiotomy on the VAS scale in all cases was 4.2 +/- 2.3 cm. Most people (97%) were satisfied with their episiotomy repair. Comparing the two groups of EMLA and lidocaine, there was no difference between the two groups in terms of the duration of episiotomy repair, need for further analgesia, pain on the VAS scale, and satisfaction with the repair method. CONCLUSION: The findings of this study showed that the use of EMLA cream in the site of episiotomy incision in primiparous women can induce a level of analgesia equal to that of lidocaine, and cause a similar level of satisfaction. PMID- 27385971 TI - Comparison of the Effects of Two Auditory Methods by Mother and Fetus on the Results of Non-Stress Test (Baseline Fetal Heart Rate and Number of Accelerations) in Pregnant Women: A Randomized Controlled Trial. AB - OBJECTIVE: To compare the effects of two auditory methods by mother and fetus on the results of NST in 2011-2012. MATERIALS AND METHODS: In this single-blind clinical trial, 213 pregnant women with gestational age of 37-41 weeks who had no pregnancy complications were randomly divided into 3 groups (auditory intervention for mother, auditory intervention for fetus, and control) each containing 71 subjects. In the intervention groups, music was played through the second 10 minutes of NST. The three groups were compared regarding baseline fetal heart rate and number of accelerations in the first and second 10 minutes of NST. The data were analyzed using one-way ANOVA, Kruskal-Wallis, and paired T-test. RESULTS: The results showed no significant difference among the three groups regarding baseline fetal heart rate in the first (p = 0.945) and second (p = 0.763) 10 minutes. However, a significant difference was found among the three groups concerning the number of accelerations in the second 10 minutes. Also, a significant difference was observed in the number of accelerations in the auditory intervention for mother (p = 0.013) and auditory intervention for fetus groups (p < 0.001). The difference between the number of accelerations in the first and second 10 minutes was also statistically significant (p = 0.002). CONCLUSION: Music intervention was effective in the number of accelerations which is the indicator of fetal health. Yet, further studies are required to be conducted on the issue. PMID- 27385972 TI - Comparison Pregnancy Outcomes Between Minimal Stimulation Protocol and Conventional GnRH Antagonist Protocols in Poor Ovarian Responders. AB - OBJECTIVE: To compare the pregnancy outcomes achieved by in vitro fertilization (IVF) between minimal stimulation and conventional antagonist protocols in poor ovarian responders (PORs). MATERIALS AND METHODS: In this randomized controlled trial, 77 PORs undergoing IVF were selected and divided into two groups. First group was the minimal stimulation group (n = 42) receiving 100 mg/day clomiphene citrate on day 2of the cycle for 5 day that was followed by150IU/day human menopausal gonadotropin (hMG) on day 5 of the cycle. Second group was the conventional group (n = 35) receiving at least 300 IU/daygonadotropin on day 2 of the cycle. Gonadotropin-releasing hormone (GnRH) antagonist protocol was applied for both groups according to flexible protocol. Number of retrieved oocytes and chemical pregnancy rate were the main outcomes. RESULTS: There was no difference in number ofretrieved oocyte and pregnancy rate (2.79 +/- 1.96 vs. 2.20 +/- 1.71 and 5.6% vs. 4.1%; p > 0.05) between both groups. The gonadotropin dose used in the minimal stimulation group was lower than conventional group (1046 +/- 596 vs. 2806 +/- 583). CONCLUSION: Minimal stimulation protocol with lower gonadotropin used is likely to be considered as a patient- friendly and cost-effective substitute for PORs. PMID- 27385973 TI - Recombinant FSH Compared to Clomiphene Citrate as the First-Line in Ovulation Induction in Polycystic Ovary Syndrome Using Newly Designed Pens: A Randomized Controlled Trial. AB - OBJECTIVE: Since there is still controversy regarding the best first-line choice for ovulation induction (OI) other than clomiphene citrate (CC) in infertile women diagnosed with polycystic ovary syndrome (PCOS), the aim of the present study was to compare recombinant human FSH with CC as the first course of OI in these women. MATERIALS AND METHODS: In this pilot randomized controlled trial, 104 infertile women diagnosed with PCOS were randomized in two groups to receive either CC with the dose of 100mg per day from day 3 of a spontaneous or progestin induced menstruation for 5 days or rFSH with the starting dose of 50 IU daily {and weekly dose increment of as low as 12.5 IU}, on the day4 of the cycle. They were assessed during a single OI course. The pregnancy rate (PR) and live birth rate (LBR) were the primary outcomes. The follicular response, endometrial thickness, cancellation of the cycles and ovarian hyper stimulation (OHSS) rate were the secondary outcomes. RESULTS: Analyzing data of 96 patients using Chi(2) and Fischer's Exact test (44 in rFSH group and 52 in CC group), both PR and LBR were comparable in the two groups {13.6% vs. 9.6% and 11.4% vs. 9.6% respectively}, with the difference not to be significant (p > 0.05). No cases of OHSS or multiple gestations happened during the treatment course. CONCLUSION: It seems that rFSH is as efficacious as CC while not with more complications for the first-line OI in infertile women with PCOS. However, due to the limitations of the present study including the small population and the single cycle of treatment, our results did not come out to prove this and more studies with larger study population are needed to compare the cumulative PR and LBR. PMID- 27385974 TI - Isolated Vaginal Neurofibroma Presenting as Vaginal Wall Cyst: A Rare Case Report With Review of Literature. AB - Neurofibromas commonly involve peripheral nervous system. Isolated neurofibroma of vagina is very rare tumor and usually associated with Von Recklinghausen's disease. Vulva is the most frequent location of neurofibroma of genital tract followed by clitoris and labia. We present a rare case of neurofibroma of vaginal wall presented as vaginal cyst in a 52 year old female with no history of any other symptoms related to Recklinghausen's disease. Excision biopsy was done and on the histopathological examination non-encapsulated, well circumscribed mass composed of spindle shaped cells with wavy nuclei and bland nuclear chromatin was noted. Immunohistochemistry revealed strong positivity with S-100. PMID- 27385975 TI - Influence of sulfur fumigation on glycoside profile in Platycodonis Radix (Jiegeng). AB - BACKGROUND: Over recent decades, sulfur fumigation is becoming abused in processing some freshly harvested herbs used as both medicine and food, although it has been questioned whether sulfur fumigation will change the efficacy and safety of the herbs. One of the herbs commonly processed by sulfur fumigation is Platycodonis Radix (Jiegeng in Chinese). Glycosides are the main bioactive components of Jiegeng. Up to the present, no study has been carried out to evaluate the impact of sulfur fumigation on glycoside profile of Jiegeng. METHODS: A rapid and versatile ultra-high performance liquid chromatography coupled with ultra-high resolution quadrupole time-of-flight mass spectrometry (UHPLC UHD Q-TOF MS/MS) method was developed for comprehensive analysis of the glycoside profiles of sulfur-fumigated and air-dried Jiegeng samples. RESULTS: Twenty-three glycosides were detected in air-dried and sulfur-fumigated Jiegeng samples. After sulfur fumigation, the peak heights of eight glycosides, namely platycogenin A, platycodin D, platycodin D2, platycodin D3, polygalacin D, polygalacin D2, deapio-platycodin D and 3"-O-acetylplatycodin D2, remarkably decreased; while peak heights of five glycosides, namely syringin, lobetyolin, platycoside E, deapio-platycodin D2 and deapio-platycoside E, slightly increased; in addition, peaks of ten glycosides, platycodin A, platycodin C, platycodin V, platycoside C, 16-oxoplatycodin D, 2"-O-acetylpolygalacin D, 2"-O acetylpolygalacin D2, 3"-O-acetylpolygalacin D, 3"-O-acetylpolygalacin D2, and platycogenic acid B, disappeared. CONCLUSION: Sulfur fumigation caused significant changes of glycoside components of Jiegeng. Further investigations are warranted to explore how these chemical changes occurred and whether these changes would affect the efficacy and safety of Jiegeng. PMID- 27385976 TI - Psychosocial wellbeing and physical health among Tamil schoolchildren in northern Sri Lanka. AB - BACKGROUND: Mental disorders contribute to the global disease burden and have an increased prevalence among children in emergency settings. Good physical health is crucial for mental well-being, although physical health is multifactorial and the nature of this relationship is not fully understood. Using Sri Lanka as a case study, we assessed the baseline levels of, and the association between, mental health and physical health in Tamil school children. METHODS: We conducted a cross sectional study of mental and physical health in 10 schools in Kilinochchi town in northern Sri Lanka. All Grade 8 children attending selected schools were eligible to participate in the study. Mental health was assessed using the Sri Lankan Index for Psychosocial Stress - Child Version. Physical health was assessed using Body Mass Index for age, height for age Z scores and the Multi-stage Fitness Test. Association between physical and mental health variables was assessed using scatterplots and correlation was assessed using Pearson's R. RESULTS: There were 461 participants included in the study. Girls significantly outperformed boys in the MH testing t (459) = 2.201, p < 0.05. Boys had significantly lower average Body Mass Index for age and height for age Z scores than girls (BMI: t (459) = -4.74, p <0.001; Height: t (459) = -3.54, p < 0.001). When compared to global averages, both sexes underperformed in the Multi Stage Fitness Test, and had a higher prevalence of thinness and stunting. We identified no meaningful association between the selected variables. CONCLUSIONS: Our results do not support the supposition that the selected elements of physical health are related to mental health in post-conflict Sri Lanka. However, we identified a considerable physical health deficit in Tamil school children. PMID- 27385977 TI - The IL-23/IL-22/IL-18 axis in murine Campylobacter jejuni infection. AB - BACKGROUND: Human Campylobacter jejuni infections are worldwide on the rise. Information about the distinct molecular mechanisms underlying campylobacteriosis, however, are scarce. In the present study we investigated whether cytokines including IL-23, IL-22 and IL-18 sharing pivotal functions in host immunity were involved in mediating immunopathological responses upon C. jejuni infection. RESULTS: To address this, conventionally colonized IL-23p19(-/ ), IL-22(-/-) and IL-18(-/-) mice were perorally infected with C. jejuni strain ATCC 43431. Respective gene-deficient, but not wildtype mice were susceptible to C. jejuni infection and could be readily colonized with highest pathogenic loads in the terminal ileum and colon at day 14 postinfection (p.i.). In IL-23p19(-/-), IL-22(-/-) and IL-18(-/-) mice viable C. jejuni were detected in MLNs, but did not translocate to spleen, liver, kidney and blood in the majority of cases. Susceptible IL-22(-/-), but neither IL-23p19(-/-), nor IL-18(-/-) mice harbored higher intestinal commensal E. coli loads when compared to resistant wildtype mice. Alike C. jejuni, commensal E. coli did not translocate from the intestinal to extra-intestinal tissue sites. Despite C. jejuni infection, mice lacking IL 23p19, IL-22 or IL-18 exhibited less apoptotic cells, but higher numbers of proliferating cells in their colonic epithelium as compared to wildtype mice at day 14 p.i. Less pronounced apoptosis was parallelled by lower abundance of neutrophils within the colonic mucosa and lamina propria of infected IL-23p19(-/ ) and IL-22(-/-) as compared to wildtype control mice, whereas less distinct colonic TNF secretion could be measured in IL-22(-/-) and IL-18(-/-) than in wildtype mice at day 14 p.i. Notably, in infected IL-22(-/-) mice, colonic IL 23p19 mRNA levels were lower, whereas the other way round, colonic IL-22 expression rates were lower in IL-23p19(-/-) mice as compared to wildtype controls. Moreover, IL-18 mRNA was less distinctly expressed in large intestines of naive and infected IL-22(-/-) mice, but not vice versa, given that IL-22 mRNA levels did not differ between in IL-18(-/-) and wildtype mice. CONCLUSION: Cytokines belonging to the IL-23/IL-22/IL-18 axis mediate immunopathological responses upon murine C. jejuni infection in a differentially orchestrated manner. Future studies need to further unravel the underlying regulatory mechanisms orchestrating pathogenic-host interaction. PMID- 27385978 TI - Rapamycin-induced autophagy sensitizes A549 cells to radiation associated with DNA damage repair inhibition. AB - BACKGROUND: Autophagy has been reported to increase in cancer cells after radiation. However, it remains unknown whether increased autophagy as a result of radiation affects DNA damage repair and sensitizes cancer cells. In this study, the radiosensitization effect of rapamycin, a mammalian target of rapamycin inhibitor that induces autophagy, on human lung adenocarcinoma A549 cells was investigated. METHODS: A549 cells were treated with different concentrations of rapamycin. Cell viability was evaluated by methyl-thiazolyl-tetrazolium assay. Survival fraction values of A549 cells after radiotherapy were detected by colony formation assay. Autophagosome was observed by a transmission electron microscope. Furthermore, Western blot was employed to examine alterations in autophagy protein LC3 and p62, DNA damage protein gamma-H2AX, and DNA damage repair proteins Rad51, Ku70, and Ku80. Rad51, Ku70, and Ku80 messenger ribonucleic acid (mRNA) expression levels were examined by real-time polymerase chain reaction. RESULTS: Rapamycin suppressed A549 cell proliferation in dose and time-dependent manners. An inhibitory concentration (IC) 10 dose of rapamycin could induce autophagy in A549 cells. Rapamycin combined with radiation significantly decreased the colony forming ability of cells, compared with rapamycin or radiation alone. Rapamycin and radiation combined increased gamma H2AX expression levels and decreased Rad51 and Ku80 expression levels, compared with single regimens. However, rapamycin treatment did not induce any change in Rad51, Ku70, and Ku80 mRNA levels, regardless of radiation. CONCLUSIONS: These findings indicate that increasing autophagy sensitizes lung cancer cells to radiation. PMID- 27385979 TI - Body mass index and long-term risk of death from esophageal squamous cell carcinoma in a Chinese population. AB - BACKGROUND: Studies based on Western populations have found that body mass index (BMI) is positively related to the risk of esophageal adenocarcinoma but inversely associated with esophageal squamous cell carcinoma (ESCC). Little reliable evidence exists of an association between BMI and ESCCin China, where ESCC incidence is high but BMI is low. METHODS: We evaluated the BMI-ESCC association in a population-based prospective study of 29 446 Chinese aged 40-69 with 27 years of follow-up. China-specific BMI cut-offs (underweight < 18.5, healthy >= 18.5 to <24, overweight >= 24 to <28, and obese >= 28) and quartile categories were used to define BMI subgroups. Adjusted hazard ratios (HRs) and confidence intervals (CIs) for death from ESCC by BMI subgroups were calculated using Cox proportional hazards models. RESULTS: During a median follow-up duration of 21.2 years (555 439 person-years), 2436 ESCC deaths were identified. BMI was protective for death from ESCC with an HR of 0.97 (95% CI 0.95-0.99) for each unit increase in BMI. Relative to healthy weight, HRs for BMI were 1.21 (95% CI 1.02-1.43) for the underweight group and 0.87 (95% CI 0.78-0.98) for the overweight. Categorical quartile analyses found people with BMIs in the Q3 and Q4 groups had 16% and 13% reductions in the risk of ESCC, respectively. Gender specific analyses found that clear effects were evident in women only. CONCLUSIONS: Higher BMI was associated with a reduced risk of ESCC in aChinese population. PMID- 27385980 TI - Predictors of survival in patients who underwent video-assisted thoracic surgery talc pleurodesis for malignant pleural effusion. AB - BACKGROUND: Patients with malignant pleural effusion have a limited life expectancy. An increase in pleural and oncological treatment options and more accurate prognostic evaluation may help individualize treatment strategies. The aim of this study was to identify the prognostic indicators of overall survival (OS) after video-assisted thoracic surgery (VATS) talc pleurodesis for malignant pleural effusion. METHODS: We examined the medical records of all consecutive patients with malignant pleural effusion who underwent VATS talc pleurodesis from 2006 to 2008 at the Samsung Medical Center. Univariate and multivariate analyses were used to identify predictors of OS after VATS talc pleurodesis. RESULTS: During the study period, 91 patients underwent VATS talc pleurodesis to treat malignant pleural effusion. Early (within 30 days) and late (within 90 days) postoperative mortality rates were 9.9% (9 patients), and 25.3% (23), respectively. Median survival time after VATS talc pleurodesis was 10.5 months. The postoperative respiratory complication rate was 11% (10 patients), and included pneumonia (9) and acute respiratory distress syndrome (4). Multivariate analysis revealed that preoperative chemotherapy (P = 0.012), preoperative radiotherapy (P = 0.003), and Eastern Cooperative Oncology Group (ECOG) performance score 3 or 4 (P = 0.013) were independent risk factors of OS after VATS talc pleurodesis. CONCLUSIONS: We identified previous chemotherapy or radiotherapy and poor performance status (ECOG 3 or 4) as significant predictors of OS after VATS talc pleurodesis. These prognostic factors can help surgeons select candidates for VATS pleurodesis for malignant pleural effusion. PMID- 27385981 TI - Exploration of optimal time for initiating adjuvant chemotherapy after surgical resection: A retrospective study in Chinese patients with stage IIIA non-small cell lung cancer in a single center. AB - BACKGROUND: Adjuvant chemotherapy (ACT) can reduce the risk of recurrence and improve survival after surgical resection in non-small cell lung cancer (NSCLC) patients. We explore the optimal time from surgery to initiation of ACT in Chinese patients with stage IIIA NSCLC. METHODS: Patients pathologically diagnosed with IIIA NSCLC who underwent radical surgery were included in this study. The cut-off point of time to initiation of adjuvant chemotherapy (TTAC) was determined by maximally selected log-rank statistics. Patients were divided into two groups according to the TTAC cut-off point. Propensity score matching (PSM) was used to eliminate confounding variables, and Kaplan-Meier analysis was used to analyze the impact of TTAC on disease-free survival (DFS). RESULTS: The cut-off time was 46 days from surgery to the first ACT. Prior to PSM, baseline characteristic variables were balanced with no statistical difference between the groups, except for pathologic subtype and smoking history. No difference in DFS was found between the two groups prior to PSM (P = 0.529); after PSM, the median DFS was consistent between the two (P = 0.822). N2 lymph node station involvement was an independent factor associated with poor survival compared with patients with N0 lymph node involvement. Moderate differentiation and postoperative radiotherapy could improve survival; however, TTAC was not significantly correlated with DFS. Subgroup analyses showed no significant correlation between DFS and different TTAC programs. CONCLUSION: No survival difference was obtained as to when ACT was initiated for patients with stage IIIA NSCLC. PMID- 27385982 TI - Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is especially beneficial to patients with exon 19 deletion compared with exon 21 L858R mutation in non-small-cell lung cancer: Systematic review and meta analysis. AB - BACKGROUND: The correlation between epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and EGFR sensitive mutation subtypes in advanced or metastatic non-small cell lung cancer (NSCLC) remains uncertain. We performed this meta-analysis to determine different clinical outcomes between patients with exon 19 deletion accepting EGFR-TKI therapy compared with those with exon 21 L858R mutation. METHODS: PubMed and Web of Science were analyzed for eligible trials. Raw data were extracted to give pooled estimates of the effect of EGFR TKI therapy on objective response rate (ORR), one-year progression-free survival (PFS), and two-year overall survival (OS). RESULTS: We identified 13 eligible trials involving 912 patients. Prospective meta-analysis demonstrated that the ORR of the 19 deletion group was significantly higher than the 21 L858R mutation group (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.18-3.33; P = 0.01), but no statistical significance between the one-year PFS rate of the 19 deletion and 21 L858R groups (OR 1.44, 95% CI 0.96-2.18; P = 0.08) was found. However, retrospective meta-analysis demonstrated that a significantly higher one-year PFS rate was associated with the 19 deletion group (OR 1.73, 95% CI 1.17-2.56; P = 0.006). The two-year survival rate of the 19 deletion group was significantly higher than the 21 L858R group (OR 5.27, 95 % CI 1.76-15.71; P = 0.003). CONCLUSIONS: In advanced NSCLC patients, an exon 19 deleton may provide superior ORR, PFS, and OS after EGFR-TKI treatment compared with an exon 21 L858R mutation. PMID- 27385983 TI - Prognostic significance of RelB overexpression in non-small cell lung cancer patients. AB - BACKGROUND: Lung cancer is a major public health issue in most countries, including China. The expression of RelB is associated with poor prognosis in diverse cancers. However, whether RelB expression could be an indicator of poor prognosis in non-small cell lung cancer (NSCLC) is still unclear. METHODS: The expression of RelB in NSCLC tumor tissue and adjacent non-neoplastic tissues were examined by immunohistochemistry. Chi-square or two-tailed Fisher's exact tests were used to analyze possible associations between qualitative clinicopathological variables and RelB expression. Kaplan-Meier analysis and a Cox regression model were employed to determine independent prognostic factors. RESULTS: The expression of RelB was increased in tumor tissue compared with adjacent non-neoplastic tissue in NSCLC patients. High RelB expression was significantly correlated with degree of differentiation (P = 0.023), depth of tumor invasion (P < 0.001), lymph node metastasis (P = 0.017), distant metastases (P = 0.004), and tumor node metastasis stage (P < 0.001) in patients with NSCLC. NSCLC patients with high RelB expression had significantly shorter overall survival than those with low RelB expression (P < 0.001). Our results indicate that high RelB expression is an independent prognostic factor for patients with NSCLC (P < 0.001). CONCLUSIONS: High RelB expression could provide a basis for judgment of prognosis in patients with NSCLC. PMID- 27385984 TI - Pilot study of radiofrequency hyperthermia in combination with gefitinib in gefitinib-effective patients with advanced NSCLC. AB - BACKGROUND: Non-small-cell lung cancer (NSCLC) is the leading cause of death from cancer in China. Gefitinib is effective for patients with positive epidermal growth factor receptor gene mutation; however, acquired drug resistance counteracts the duration response. Hyperthermia is widely clinically applied in the treatment of solid tumors. This pilot study was designed to evaluate the feasibility of the combination of gefitinib and hyperthermia. METHODS: Patients newly diagnosed with advanced NSCLC were screened. Eleven patients who responded to first-line gefitinib treatment were enrolled in the study. Along with 250 mg gefitinib daily, local radiofrequency hyperthermia was administered twice a week until tumor progression was observed. The serum, heat shock protein (HSP)70, was also frequently detected during the course. RESULTS: The most common toxicity included skin rash (81.8%) and abnormal liver function (45.5%) when treated with gefitinib, and fatty scleroma (36.4%) was observed when combined with hyperthermia. Grade 3 side effects (skin rash) occurred in only one patient. Median progression-free survival was 22 months (95% confidence interval [CI]: 12.95-31.05 months) and median overall survival was 26 months (95% CI: 22.81 29.19 months). Serum HSP70 concentration increased and maintained a significantly high level compared with the baseline before hyperthermia administration. CONCLUSIONS: The novel therapy of gefitinib combined with radiofrequency hyperthermia is safe and effective for advanced NSCLC patients. Whether an improvement in therapeutic efficacy is associated with the elevation of serum HSP70 concentration requires further study. PMID- 27385985 TI - Evaluation of a novel saliva-based epidermal growth factor receptor mutation detection for lung cancer: A pilot study. AB - BACKGROUND: This article describes a pilot study evaluating a novel liquid biopsy system for non-small cell lung cancer (NSCLC) patients. The electric field induced release and measurement (EFIRM) method utilizes an electrochemical biosensor for detecting oncogenic mutations in biofluids. METHODS: Saliva and plasma of 17 patients were collected from three cancer centers prior to and after surgical resection. The EFIRM method was then applied to the collected samples to assay for exon 19 deletion and p.L858 mutations. EFIRM results were compared with cobas results of exon 19 deletion and p.L858 mutation detection in cancer tissues. RESULTS: The EFIRM method was found to detect exon 19 deletion with an area under the curve (AUC) of 1.0 in both saliva and plasma samples in lung cancer patients. For L858R mutation detection, the AUC of saliva was 1.0, while the AUC of plasma was 0.98. Strong correlations were also found between presurgery and post-surgery samples for both saliva (0.86 for exon 19 and 0.98 for L858R) and plasma (0.73 for exon 19 and 0.94 for L858R). CONCLUSION: Our study demonstrates the feasibility of utilizing EFIRM to rapidly, non-invasively, and conveniently detect epidermal growth factor receptor mutations in the saliva of patients with NSCLC, with results corresponding perfectly with the results of cobas tissue genotyping. PMID- 27385986 TI - Icotinib as initial treatment in lung adenocarcinoma patients with brain metastases. AB - BACKGROUND: To evaluate the antitumor activity and toxicity of icotinib as initial treatment in lung adenocarcinoma patients with brain metastases. METHODS: Twenty-one patients with histologically or pathologically documented brain metastatic lung cancer were administered icotinib as initial treatment from 2011 to 2015 at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences. Chemotherapy response was assessed by Response Evaluation Criteria in Solid Tumors and toxicity was evaluated according to National Cancer Institute Common Toxicity Criteria. Icotinib was administered three times per day at a dose of 125mg. RESULTS: The median overall and progression-free survival rates were 15.2 (1.2-31.5 months, 95% confidence interval [CI] 6.6-23.7 months) and 8.9 months (0.6-30.5 months, 95% CI 3.4-14.3 months), respectively. The overall response and disease control rates were 61.9% and 90.5%, respectively. Icotinib was well tolerated, and no grade 3/4 adverse events were observed. The most common grade 1/2 adverse events included acneiform eruptions (38.1%), diarrhea (19.0%), and stomatitis (9.5%). CONCLUSION: Icotinib is effective and well tolerated as initial treatment in lung adenocarcinoma patients with brain metastases. PMID- 27385987 TI - Clinical outcomes of video-assisted thoracic surgery and stereotactic body radiation therapy for early-stage non-small cell lung cancer: A meta-analysis. AB - BACKGROUND: We compared video-assisted thoracoscopic surgery (VATS) lobectomy and stereotactic body radiation therapy (SABR) to explore clinical outcomes in the treatment of patients with early stage NSCLC. METHODS: Major medical databases were systematically searched to identify studies on VATS and SBRT published between January 2010 and October 2015. English publications of stage I and II NSCLC with adequate patients and SBRT doses were included. A multivariate random effects model was used to perform meta-analysis to compare overall survival (OS) and disease-free survival (DFS) between VATS and SBRT, adjusting for median age and operable patient numbers. RESULTS: Thirteen VATS (3436 patients) and 24 SBRT (4433) studies were eligible. The median age and follow-up duration was 68 years and 42 months for VATS and 74 years and 29.4 months for SBRT patients. After adjusting for the proportion of operable patients and median age, the estimated OS rates at one, two, three, and five years with VATS were 94%, 89%, 84%, and 69% compared with 96%, 94%, 89%, and 82% for SBRT. The estimated DFS rates at one, two, three, and five years with VATS were 97%, 93%, 87%, and 77% compared with 86%, 80%, 73%, and 58% for SBRT. CONCLUSION: Before adjustment, patients treated with SBRT had poorer clinical outcomes compared to those treated with VATS. A substantial difference between median age and operability exists between patients treated with SBRT and VATS. After adjusting for these differences, OS and DFS did not differ significantly between the two techniques. PMID- 27385988 TI - Clinical effect of pemetrexed as the first-line treatment in Chinese patients with advanced anaplastic lymphoma kinase-positive non-small cell lung cancer. AB - BACKGROUND: The efficacy of pemetrexed-based first-line chemotherapy in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) has been demonstrated in several studies; however, there is a lack of data from Chinese populations. METHODS: The clinicopathological characteristics and treatment outcomes of 52 patients with ALK-positive advanced NSCLC who received pemetrexed as first-line chemotherapy at the Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively reviewed. The primary end points were response rate and progression-free survival (PFS). RESULTS: The gender proportion was balanced and the median age was 51 years (range 26-76). Of the 52 patients, 46 (88.5%) had stage IV disease, predominantly adenocarcinoma (98.1%). Sixteen patients were current/former smokers and 36 were never/light smokers. The most common sites of metastasis were the pleura (36.5%), bone (30.8%), lung (26.9%), and brain (17.3%). The median PFS was 9.5 months (95% confidence interval 7.454-11.536). At the time of analysis, partial remission was achieved in 18 (34.6%) patients, stable disease in 26 (50.0%), and progressive disease in eight (15.4%); none of the patients achieved complete remission. The objective response rate was 34.6% and the disease control rate was 84.6%. Common adverse events with pemetrexed were neutropenia (53.8%), nausea and vomiting (51.9%), leukopenia (32.7%), and fatigue (25.0%), mainly at grades 1 or 2. CONCLUSIONS: Pemetrexed is efficient and tolerated as first-line treatment for ALK-positive NSCLC in a cohort of Chinese patients and may prove to be an alternative option for the treatment of ALK-positive NSCLC. PMID- 27385989 TI - Fibrobronchoscopic cryosurgery for secondary malignant tumors of the trachea and main bronchi. AB - BACKGROUND: Patients with secondary malignant tracheal and main bronchial tumors may suffer severe symptoms as a result of major airway obstruction. Curative surgical resection is usually not suitable because of the presence of metastatic disease and poor performance status. In this study, the use of bronchoscopic cryosurgery to reopen the airway is analyzed. METHODS: The clinical records of 37 patients who experienced secondary maglinancies from December 2001 to January 2013 were retrospectively reviewed. Low temperature cryotherapy (-50 degrees C to -70 degrees C) was delivered to the central part of the tumor by cryoprobe for four to six minutes causing destruction of the tumor mass (Cryo-melt method). Subsequently, the edge of the tumor was frozen for 30 seconds to two minutes, followed by piecemeal removal of the frozen tumor tissue (Cryo-resection method). RESULTS: The endpoints of the study were degree of symptomatic improvement and survival. The rates of dramatic and partial symptomatic alleviation were 57.1% and 28.6%, respectively, there were no intraoperative deaths, and median survival was 16.0 months. Prolonged survival was significantly correlated to age (under 60 years of age 22.2% vs. over 60 100%, P = 0.011), tumor location (main bronchi 0% vs. trachea 77.8%, P = 0.003), and cryorecanalization times (once 33.3% vs. twice or more 80.0%, P = 0.037). CONCLUSION: Bronchoscopic cryorecanalization is a safe, effective, non-invasive choice for improving the symptoms of malignant airway obstruction. In addition to achieving local-regional control, the technique may also contribute to improved survival. PMID- 27385990 TI - Prospective study of the UGT1A1*27 gene polymorphism during irinotecan therapy in patients with lung cancer: Results of Lung Oncology Group in Kyusyu (LOGIK1004B). AB - BACKGROUND: Uridine 5'-diphospho-glucuronosyltransferase 1A1 (UGT1A1*27) is known to impair the effect of UGT in basic research; however, little clinical investigation has been conducted. To evaluate the effect of the UGT1A1*27 polymorphism in irinotecan therapy, we conducted a prospective study. METHODS: Eligibility criteria included: lung cancer patients; scheduled irinotecan therapy doses of single >= 80, combination >= 50, radiation with single >= 50, or radiation with combination >= 40 mg/m(2); age >= 20; and Eastern Cooperative Oncology Group performance score (PS) 0-2. Patients were examined for UGT1A1*28 and *6 polymorphisms and received irinotecan. When the UGT1A1*28 polymorphism was detected, a search for UGT1A1*27 was conducted. Fifty patients were enrolled, with 48 patients determined eligible. RESULTS: UGT1A1 polymorphisms *28/*28, *6/*6, *28/*6, *28/-, *6/-, -/- observed 0 (0%), 1 (2%), 1 (2%), 7 (15%), 17 (35%) and 22 (46%), respectively. UGT1A1*27 were examined in nine patients including one ineligible patient; however, no polymorphisms were found. The study ceased after interim analysis. In an evaluation of the side effects of irinotecan, patients with UGT1A1*28 and UGT1A1*6 polymorphisms had a higher tendency to experience febrile neutropenia than wild type (25% and 32% vs. 14%). Incidences of grade 3/4 leukopenia and neutropenia were significantly higher in patients with UGT1A1*28 polymorphisms compared with wild type (75% vs. 32%, P = 0.049; 75% vs. 36%, P = 0.039, respectively). CONCLUSION: Our prospective study did not locate the UGT1A1*27 polymorphism, suggesting that UGT1A1*27 does not significantly predict severe irinotecan toxicity in cancer patients. PMID- 27385991 TI - Identification of false-negative and false-positive diagnoses of lymph node metastases in non-small cell lung cancer patients staged by integrated (18F )fluorodeoxyglucose-positron emission tomography/computed tomography: A retrospective cohort study. AB - BACKGROUND: The aim of this study was to evaluate the diagnostic accuracy of integrated (18) F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in hilar and mediastinal lymph node (HMLN) staging of non small cell lung cancer (NSCLC), and to investigate potential risk factors for false-negative and false-positive HMLN metastases. METHODS: We examined the data of 388 surgically resected NSCLC patients preoperatively staged by integrated FDG PET/CT. Risk factors for false-negative and false-positive HMLN metastases were analyzed using univariate and multivariate analyses of clinicopathological factors. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of integrated FDG-PET/CT in detecting HMLN metastases were 47.4%, 91.0%, 56.3%, 87.7%, and 82.5%, respectively. On multivariate analysis, the maximum standardized uptake value (SUVmax) of the tumor (P = 0.042), adenocarcinoma (P = 0.003), and tumor size (P = 0.017) were risk factors for false-negative HMLN metastases, and history of lung disease (P = 0.006) and tumor location (central; P = 0.025) were risk factors for false positive HMLN metastases. CONCLUSIONS: The present study identified risk factors for false-negative and false-positive HMLN metastases in NSCLC patients staged by preoperative integrated FDG-PET/CT. These findings would be helpful in selecting appropriate candidates for mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration. PMID- 27385992 TI - Small activating ribonucleic acid reverses tyrosine kinase inhibitor resistance in epidermal growth factor receptor-mutant lung cancer by increasing the expression of phosphatase and tensin homolog. AB - BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (TKI EGFRs) present a new prospect for the treatment of lung cancer. However, in clinical application, the majority of patients become TKI resistant within a year. More and more studies have shown that a loss of phosphatase and tensin homolog (PTEN) expression is associated with TKI resistance. An alternative method of upregulating PTEN expression may reverse TKI resistance. METHODS: We designed five candidate small activating ribonucleic acids (saRNAs) to target PTEN, and transfected them into H-157 cells to screen out functional saRNA. We used reverse transcriptase-polymerase chain reaction and Western blot to evaluate the effect of saRNA to PTEN expression. We then analyzed the growth and apoptosis of cells transfected with saRNA under the treatment of TKI to investigate whether saRNAs can reverse TKI resistance by upregulating PTEN expression. RESULTS: The functional saRNA we designed could upregulate PTEN expression. The H-157 cells transfected with saRNA grew slower in the presence of TKI drugs than the cells that were not transfected with saRNA. The apoptosis rate was also obviously higher. CONCLUSIONS: Our study proves that loss of PTEN expression is an important mechanism of TKI resistance. It is possible to control TKI resistance by upregulating PTEN expression using RNA activation technology. PMID- 27385993 TI - Topoisomerase I expression is associated with prognosis in postoperative non small cell lung cancer patients. AB - BACKGROUND: Biomarkers may help to improve non-small cell lung cancer (NSCLC) prognosis. However, the prognostic effect of topoisomerase I (Topo I) on NSCLC is unknown. We evaluated the clinicopathologic and prognostic significance of tumor Topo I and thymidylate synthase (TS) protein expression in postoperative NSCLC patients. METHODS: One hundred and fifteen patients with postoperative NSCLC were enrolled. Topo I and TS protein were detected in removed tumors by immunohistochemistry. The correlations between Topo I/TS protein expression and clinicopathologic characters and outcomes of patients were analyzed. RESULTS: Increased expression of Topo I was found in 57 (49.6%) tumors. The largest diameter of the tumor was significantly different between patients with high and low Topo I expression (P = 0.035). TS staining showed that 35 (30.4%) carcinomas were TS positive. The level of TS expression was correlated with tumor differentiation (P = 0.037). Patients with low Topo I expression had significantly longer overall survival (OS) than those with high expression (P = 0.004). The correlation between Topo I expression and OS was demonstrated among patients with squamous cell carcinoma (P = 0.030) and patients in pathological tumor node metastasis stage I (P = 0.027). Topo I expression was positively correlated with TS expression in tumor tissue (R = 0.251, P = 0.007). CONCLUSIONS: Low Topo I expression is an independent favorable prognostic factor for longer OS in postoperative NSCLC patients, especially in squamous cell carcinoma. There is a correlation between the expression of TS and Topo I in removed tumor tissue. PMID- 27385994 TI - Thoracoscopic tracheal reconstruction without surgical field intubation. AB - A cross-filed endotracheal intubation is usually applied to maintain single lung ventilation during both open and thoracoscopic tracheal resection and reconstruction. Herein, we report a case of thoracoscopic tracheal resection and reconstruction with interrupted ventilation via transoral endotracheal intubation in a patient with thoracic tracheal adenocarcinoma. Tracheal anastomosis was accomplished using a running suture with a 3-0 Prolene stitch. PMID- 27385995 TI - Gefitinib for asymptomatic brain metastasis from advanced non-small cell lung cancer: Report of a favourable outcome. AB - Brain metastasis (BM) is common in patients with non-small cell lung cancer (NSCLC). Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have now been included as standard treatment options for NSCLC harboring EGFR-activating mutations, only a few prospective reports demonstrate the efficacy of these agents in a BM setting. We report a case of a patient with advanced NSCLC, in which oral gefitinib documented a significant antitumor effect on parallel progression of extracranial lesion and BM occurred during chemotherapy. PMID- 27385996 TI - Pulmonary malignant melanoma with distant metastasis assessed by positron emission tomography-computed tomography. AB - Melanoma is a cutaneous malignant neoplasm of melanocytes. Primary malignant melanoma (MM) of the lung is very rare. Although previous reports have described the radiologic features of pulmonary MM, its rarity means that many factors are unknown. Thus, radiologic diagnosis is very difficult. Furthermore, there is little information regarding diagnostic application and/or the usefulness of [(18)F]-fluorine-2-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (FDG-PET-CT) for primary pulmonary MM. A 69-year-old patient with a productive cough lasting three weeks was admitted to our hospital. Chest CT showed a large single mass with a multi-lobulated margin and homogeneous enhancement in the right upper lobe, which was subsequently diagnosed as a primary pulmonary MM with multiple metastases. On PET-CT images, the pulmonary mass and multiple bone lesions showed very increased uptakes of FDG. Considering that pulmonary metastasis from a mucocutaneous melanoma is the main differential diagnosis of primary pulmonary MM, systemic assessment of the whole body is more important than for other types of lung malignancies. This report introduces PET CT as a useful diagnostic modality for pulmonary MM, especially in cases of distant multiple metastases. PMID- 27385997 TI - Pulmonary sclerosing pneumocytoma mimicking lung cancer: Case report and review of the literature. AB - Pulmonary sclerosing pneumocytoma (PSP) is a rare benign neoplasm that predominantly affects middle-aged Asian women. PSP is often asymptomatic and demonstrates a solitary pulmonary nodule on radiologic examination. We report a case of PSP initially misdiagnosed as lung cancer because of strong (18)F fluorodeoxyglucose (FDG) uptake revealed by (18)F-FDG positron emission tomography-computed tomography scan. After surgery, pathology revealed that the tumor cells were immunopositive for epithelial membrane antigen and thyroid transcription factor-1. The patient has been followed up without complication or recurrence. PMID- 27385998 TI - Effect of CO2, Nd:YAG and Er:YAG Lasers on Microtensile Bond Strength of Composite to Bleached-Enamel. AB - BACKGROUND: Tooth restoration immediately after bleaching is challenging due to the potential problems in achieving adequate bond strength. OBJECTIVE: The aim of this study was to evaluate the effect of surface treatment with ER:YAG, ND:YAG, CO2 lasers and 10% sodium ascorbate solution on immediate microtensile bond strength of composite resin to recently bleached enamel. MATERIALS & METHODS: Ninety sound molar teeth were randomly divided into three main groups (n:30) : NB (without bleaching), HB (bleached with 38% carbamide peroxide) and OB (bleached with Heydent bleaching gel assisted by diode laser). Each group was divided into five subgroups (n:6) : Si (without surface treatment), Er (Er:YAG laser), CO2 (CO2 laser), Nd (Nd:YAG laser) and As (Immersion in 10% sodium ascorbate solution). The bonding system was then applied and composite build-ups were constructed. The teeth were sectioned by low speed saw to obtain enamel- resin sticks and submitted to microtensile bond testing. Statistical analyses were done using two- way ANOVA, Tukey and Tamhane tests. RESULTS: uTBS of bleached teeth irradiated with ND:YAG laser was not significantly different from NB-Nd group. Microtensile bond strength of OB-Er group was higher than NB-Er and HB-Er groups. The mean uTBS of HB-CO2 group was higher than NB-CO2 group; the average uTBS of HB-As and OB-As groups was also higher than NB-As group. CONCLUSION: Use of Nd:YAG, CO2 lasers and 10% sodium ascorbate solution could improve the bond strength in home-bleached specimens. Application of ND:YAG laser on nonbleached specimens and Er:YAG laser on office-bleached specimens led to the highest uTBS in comparison to other surface treatments in each main group. PMID- 27385999 TI - Editorial: Natural Products in Oral Health. PMID- 27386000 TI - Evaluation of the Antibacterial Efficacy of Azadirachta Indica, Commiphora Myrrha, Glycyrrhiza Glabra Against Enterococcus Faecalis using Real Time PCR. AB - AIM: To compare the antibacterial efficacy of Azadirachta indica (Neem), Commiphora myrrha (Myrrh), Glycyrrhiza glabra (Liquorice) with 2% Chlorhexidine (CHX) against E. faecalis by using Real Time PCR. MATERIALS AND METHODS: A total of fifty teeth specimens (n=50) were inoculated with E. faecalis for 21 days. Specimens were divided into five groups (Group 1: Myrrh, Group 2: Neem, Group 3: Liquorice, Group 4: 2% CHX and Group 5: Saline (negative control)). The intracanal medicaments were packed inside the tooth. After 5 days, the remaining microbial load was determined by using real time PCR. RESULTS: Threshold cycle (Ct) values of Myrrh extract, Neem extract, Liquorice Extract, 2% CHX and saline were found to be 30.94, 23.85, 21.38, 30.93 and 17.8 respectively. CONCLUSION: Myrrh extract showed inhibition of E.faecalis equal to that of 2% CHX followed by Neem, Liquorice and Saline. PMID- 27386001 TI - Green Tea (Camellia Sinensis): Chemistry and Oral Health. AB - Green tea is a widely consumed beverage worldwide. Numerous studies have suggested about the beneficial effects of green tea on oral conditions such as dental caries, periodontal diseases and halitosis. However, to date there have not been many review articles published that focus on beneficial effects of green tea on oral disease. The aim of this publication is to summarize the research conducted on the effects of green tea on oral cavity. Green tea might help reduce the bacterial activity in the oral cavity that in turn, can reduce the aforementioned oral afflictions. Furthermore, the antioxidant effect of the tea may reduce the chances of oral cancer. However, more clinical data is required to ascertain the possible benefits of green tea consumption on oral health. PMID- 27386003 TI - Dentin Cleaning Ability of an Amazon Bioactive: Evaluation by Scanning Electron Microscopy. AB - The role of dentin cleaning is to remove debris that may impair adaptation and marginal sealing, quantitatively reducing microorganisms. The aim of this study was to investigate through scanning electron microscopy (SEM) the morphology of the dentin surface, cut and treated with copaiba oil emulsions (CO) and suspension of ethanol extract of propolis (EP). Twenty four upper pre-molars teeth, divided into eight groups (n=3), were used: G1: no cleaning, G2: air/water spray, G3: 10% CO, G4: 10% CO + A, G5: 30% CO, G6: 30% CO + A, G7: 1% EP, G8: 2% Chlorhexidine. The specimens were dentin discs (1 mm O). The SEM photomicrographs were classified and the results were: G1 - Debris dentin on the entire image / countless microorganisms, G2 and G7 - 50-100 debris / countless microorganisms and G3, G4, G5, G6 and G8 - 0-50 debris / countable microorganisms (50-100 colonies). CONCLUSION: The present results suggest that copaiba oil emulsions (CO) and suspension of ethanol extract of propolis (EP) have feasibility to be used as bioactive dental cleaning agents. PMID- 27386002 TI - Platelet Rich Fibrin in Periodontal Regeneration. AB - Periodontitis is a chronic bacterial infection resulting in destruction of the supporting structures of the teeth. Regeneration of the lost tissues has faced difficulties primarily due to the lack of support during the intricate healing processes. A surgical additive which can 'jump start' the healing process to a more predictable regenerative process is always on the wish list of any periodontist. Platelet-rich fibrin (PRF) is a second generation platelet concentrate that has been considered to be an important, easy to obtain, predictable surgical additive for periodontal regeneration. This autologous scaffold provides the much needed bio-chemical mediators which has the potential for enhancing reconstruction of the periodontium. This review article tries to understand as to why PRF would be an important link to reach predictable periodontal regeneration. PMID- 27386004 TI - Antibacterial Activity of Copaiba Oil Gel on Dental Biofilm. AB - Amazonian biodiversity products that have been used for years in folk medicine, have emerged as feasible and promising alternatives for the inhibition of microorganisms in dental biofilm. Copaiba oil, a phytotherapic agent widely used by the Amazonian populations, is known for its antibacterial, anti-inflammatory, anesthetic, healing and antitumor medicinal properties. OBJECTIVE: The aim of this study was to evaluate the in vitro antibacterial activity of copaiba oil (Copaifera multijuga) gel against strains of Streptococcus sp present in dental biofilm. MATERIALS AND METHODS: The copaiba oil was obtained and the chemical components were identified. The oil emulsions were formulated and used with the Brain Heart Infusion agar diffusion method with strains of Streptococcus mitis, Streptococcus constellatus and Streptococcus salivarius isolated from patients as well as standard strains of S. mitis (ATCC903), S. mutans (ATCC10449), S. sanguinis (ATCC15300) and S. oralis (ATCC10557). The study groups were as follows: experimental copaiba oil gel, 1% chlorhexidine gel (positive control) and base gel (negative control). The seeded plates were incubated at 37oC for 12, 24 and 48 hours, respectively. The results obtained were analyzed by Shapiro-Wilk and Friedman Tests (p<0.05) for non parametric data and the Tukey test was used for pH values with 5% level of significance. RESULTS: The experimental copaiba oil gel and 1% chlorhexidine gel showed antibacterial activity against the tested microorganisms. CONCLUSION: The copaiba oil gel demonstrated antibacterial activity against all the strains of Streptococcus sp tested, suggesting that it can be used for dental biofilm control. PMID- 27386005 TI - Ozone- A Biological Therapy in Dentistry- Reality or Myth????? AB - The usage of ozone in dentistry has been proposed because of its antimicrobial, disinfectant, biocompatibility and healing properties. In the last decade a number of therapeutic protocols with ozone have been developed to address common dental infections associated with periodontal disease, RCT and caries. Despite these advantages, therapeutic ozone's application in dentistry is limited because of its possible side effects. Hence, dental practitioners need to know the proper usage of ozone therapy that can provide better patient care and considerably cut down the time and cost of the treatment. PMID- 27386006 TI - Comparison of Dill Seed Oil Mouth Rinse and Chlorhexidine Mouth Rinse on Plaque Levels and Gingivitis - A Double Blind Randomized Clinical Trial. AB - INTRODUCTION: Mouthrinses have been in use for centuries as breath fresheners, medicaments, and antiseptics. Dill is said to be a good source of calcium, manganese and iron. It contains flavonoids known for their antioxidant, anti inflammatory, and antiviral properties. Dill can help with microbial infections in the mouth; and its anti-oxidants minimize damage caused by free radicals to the gums and teeth. Being a good source of calcium, dill also helps with bone and dental health. AIMS AND OBJECTIVES: To compare the effectiveness of commercially available 0.2% chlorhexidine gluconate mouthrinse and dill seed oil mouthrinse on plaque levels and gingivitis. MATERIAL AND METHODS: A randomized controlled, double blind parallel arm study was conducted over 90 days on 90 subjects. The subjects were randomly divided into 2 groups and baseline data was collected using Loe and Silness gingival index and Quigley Hein plaque index and oral prophylaxis was performed on all the subjects. The mouthrinses included in the present study were dill seed oil and Hexodent (0.2% chlorhexidine gluconate). Intervention regarding the mouthrinsing was given to the subjects and were followed up for 45 days and 90 days, after this post intervention changes were assessed using the respective indices. RESULTS: It was observed that there is no significant difference in gingival & plaque scores among two mouthrinses from baseline to 45 days and 90 days. It was observed that there is statistical difference in gingival and plaque scores when compared with baseline to 45 days (p<0.001), baseline to 90 days (p<0.001) and 45 days to 90 days (p<0.001) when intergroup comparisons were done. CONCLUSION: It was concluded that dill seed oil and Hexodent (0.2% chlorhexidine gluconate) mouthrinse have similar antiplaque and antigingival effectiveness. PMID- 27386008 TI - The Promising Applications of Stem Cells in the Oral Region: Literature Review. AB - INTRODUCTION: For a long time researchers have tried to find out a way to grow tissues back to the human body in order to solve transplantation problems by offering the unique opportunity to have their organs back, working properly, in search of life dignity. LITERATURE REVIEW: Stem cells seem to be present in many other tissues than researchers had once thought; and in some specific sites they can be easily collected, without the need of expensive interventions. The oral cavity is one of these regions where their collection can be accomplished, with plenty of accessible sites enriched with these precious cells. AIM: The aim of this literature review is to research where in the mouth can scientists find stem cells to be used in the near future. KEY-MESSAGE: The aim of this literature review is to research where stem cells can be found and collected in the oral cavity. PMID- 27386007 TI - Natural Therapeutic Options in Endodontics - A Review. AB - Complete eradication of microbial biofilms and elimination of the smear layer are the key factors during endodontic treatment. Various chemical irrigants have been proposed in the literature for the same. The major setback with these chemical irrigants is that they are not bio-friendly to the dental and peri-radicular tissues. In the recent years, research to use natural products for root canal disinfection has gained importance. The aim of this article is to compile various herbal products that have been used as an irrigants and intracanal medicaments in the field of Endodontics to eradicate the biofilm and remove smear layer. PMID- 27386009 TI - Orthodontic Treatment of Malocclusion and its Impact on Oral Health-Related Quality of Life. AB - OBJECTIVES: Malocclusion, though not life-threatening, has vast impact on individual's social interactions and self-esteem. Therefore, the aim of the current study was to assess whether orthodontic treatment of adolescents with malocclusion had any association with their oral health-related quality of life (OHRQoL). METHODS: The subjects for this study were recruited at a state-funded university clinic. Data were collected from 100 participants aged 17 to 21 with moderate to severe malocclusion. Experimental group comprised of 50 subjects who were in the retention phase of their orthodontic treatment and the control group comprised of 50 untreated subjects. The shortened version of the Oral Health Impacts Profile (OHIP-14) as used to assess the subjects' oral health-related impact. T-test, Kruskal-Wallis, and Mann Whitney tests were used to analyze the data and p-value was set at P < 0.05. RESULTS: In general, oral health-related quality of life of all subjects significantly improved after orthodontic treatment. (p<0.001) Subjects with moderate malocclusion showed better improvement than severe malocclusion subjects. (P<0.001). CONCLUSION: This study showed that oral health-related quality of life improves with the treatment of malocclusion. PMID- 27386011 TI - Torque Loss After Miniscrew Placement: An In-Vitro Study Followed by a Clinical Trial. AB - To evaluate torque loss a week after insertion, both in an in vivo and an in vitro experimental setup were designed. In the in vivo setup a total of 29 miniscrews were placed in 20 patients who underwent orthodontic treatment. Maximum insertion torque (MIT) was evaluated at insertion time (T1). A week later, insertion torque was measured again by applying a quarter turn (T2); no load was applied on the screw during the first week. In the in vitro setup a total of 20 miniscrews were placed in pig rib bone samples. MIT was evaluated at insertion time (T1). Bone samples were kept in saline solution and controlled environment for a week during which the solution was refreshed every day. Afterwards, torque was measured again by applying a quarter turn (T2). The comparison of MIT over time was done calculating the percentage difference of the torque values between pre- and post-treatment and using the parametric two independent samples t-test or the non-parametric Mann-Whitney test. After a week unloaded miniscrews showed a mean loss of rotational torque of 36.3% and 40.9% in in vitro and in in vivo conditions, respectively. No statistical differences were found between the two different setups. Torque loss was observed after the first week in both study models; in vitro experimental setup provided a reliable study model for studying torque variation during the first week after insertion. PMID- 27386010 TI - Clinical and Spectrophotometric Evaluation of LED and Laser Activated Teeth Bleaching. AB - BACKGROUND: Auxiliary power sources (LED and laser) are used in in-office teeth bleaching techniques to accelerate the redox reaction of the whitening gel to increase ease of use, to improve comfort and safety, and to decrease the procedure time. OBJECTIVE: The aim this study is to evaluate the efficiency of the teeth whitening procedures performed with hydrogen peroxide and carbamide peroxide, LED or Laser activated. METHOD: 18 patients, affected by exogenous dyschromia, were treated with a bleaching agent composed by 35% hydrogen peroxide and 10% carbamide peroxide. They were divided into two groups: in the first group the bleaching agent was activated by a LED lamp; in the second group it was activated by a Laser diode lamp. Both groups were subjected to 3 bleaching cycle of 15' each. The chromatic evaluations were performed before and after one week from the treatment, using a chromatic scale and a spectrophotometer. The mean value of pre, post bleaching and follow-up were analyzed using a T-test, with results statistically significant for P<0,05. RESULTS: Results showed that the variations in brightness, chroma and hue are significantly influenced by the interaction between the whitening agent and the original colour of the teeth. Laser-activation has marginally improved the bleaching effectiveness. All patients treated with laser activation complained an increase in dental sensitivity. CONCLUSION: The use of laser-activating systems did not improve the efficacy of bleaching. PMID- 27386012 TI - Chronic Maxillary Sinusitis Caused by Denture Lining Material. AB - We report a case of chronic maxillary sinusitis caused by denture lining material entering through an oroantral fistula after tooth extraction. The patient was an 80-year-old female who visited us with a complaint of pus discharge from the right posterior maxilla. She had extraction of the upper right second molar and had her upper denture relined with silicone lining material. The patient noticed swelling of the right cheek and purulent rhinorrhea 20 days before her first visit to our clinic. Oral examination showed an oroantral fistula with a diameter of 3 mm in the posterior alveolar ridge of the right maxilla. Computed tomography revealed a hyperdense foreign body in the right maxillary sinus and thickening of the mucosal lining. Under diagnosis of maxillary sinusitis caused by a foreign body, endoscopic maxillary surgery was performed simultaneously with the removal of the foreign body. The foreign body removed was 12 * 6 mm in size, oval in shape, light pink in color, and compatible with silicone denture lining material. During the follow-up it was observed that the oroantral fistula closed spontaneously after the removal of the foreign body. The maxillary sinus was in a good shape without recurrence of sinusitis seven months after surgery. PMID- 27386013 TI - Biological and Immunogenicity Property of IgY Anti S. mutans ComD. AB - OBJECTIVE: This study aims to elucidate the effect of IgY anti ComD on the biological properties of Streptococcus mutans. (S. mutans) ComD is an interspecies quorum-sensing signaling receptor that plays an important role in biofilm formation by S. mutans. MATERIALS AND METHODOLOGY: Egg yolk IgY was produced by the immunization of chickens with a DNA vaccine containing the ComD DNA coding region. We evaluated the effect of the antibody on biofilm formation by S. mutans isolated from subjects with or without dental caries. We also assessed the immunoreactivity of the antibody against all isolates, and analyzed the protein profile of S. mutans by SDS-PAGE. RESULTS: The ComD antibody was successfully induced in the hens' eggs. It inhibited biofilm formation by all S. mutans isolates. In addition, the expression of some protein bands was affected after exposure to the antibody. CONCLUSION: IgY anti-S. mutans ComD reduces biofilm formation by this bacterium and alters the protein profile of S. mutans. PMID- 27386014 TI - HIV Infection Care and Viral Suppression Among People Who Inject Drugs, 28 U.S. Jurisdictions, 2012-2013. AB - OBJECTIVES: Assess outcomes along the care continuum for HIV-infected people who inject drugs (PWID), by type of facility and stage of infection at diagnosis. METHODS: Data reported by 28 jurisdictions to the National HIV Surveillance System by December 2014 were used to identify PWID aged >=13 years, diagnosed with HIV infection before December 31, 2013. Analyses used the CDC definition of linkage to care (LTC), retention in care (RIC), and viral suppression (VS), and are stratified by age, sex, race/ethnicity, and type of facility and stage of HIV infection at diagnosis. RESULTS: Of 1,409 PWID diagnosed with HIV in 2013, 1,116 (79.2%) were LTC with the lowest percentages among males (78.4%); blacks (77.5%) ages 13-24 years (69.0%); those diagnosed in early stage infection (71.6%); and at screening, diagnostic, or referral agencies (60.0%). Of 80,958 PWID living with HIV in 2012, 40,234 (49.7%) were RIC and 34,665 (42.8%) achieved VS. The lowest percentages for RIC and VS were among males (47.1% and 41.3% respectively); those diagnosed with late stage disease (47.1% and 42.4%); and young people. Whites had the lowest RIC (47.0%) while blacks had the lowest VS (41.1%). CONCLUSION: Enhanced LTC activities are needed for PWID diagnosed at screening, diagnostic or referral agencies versus those diagnosed at inpatient or outpatient settings, especially among young people and blacks diagnosed in early stage infection. Less than half of PWID are retained in care or reach viral suppression indicating the need for continued engagement and return to care activities over the long term. PMID- 27386016 TI - Hematoma of the psoas muscle, in prostatic cancer patient: a case report. AB - We report a case of 64-year-old male with prostate cancer and coagulation disorder presented with abdominal distension. He underwent abdomen and pelvis ultrasound for assessment of ascites, which showed localized fluid collections identified at the left and right iliac fossa. After that, non enhanced abdomen and pelvis CT scan was performed and showed heterogeneous organized collections identified along the psoas muscles bilaterally, causing focal contour bulge representing haematoma. PMID- 27386015 TI - [Complete third nerve palsy revealing Tolosa Hunt Syndrome]. PMID- 27386017 TI - A comparative study of the diagnostic methods for Group A streptococcal sore throat in two reference hospitals in Yaounde, Cameroon. AB - INTRODUCTION: Sore throat is a common complaint in general practice which is more frequent in children. The most frequent pathogenic bacteria associated with this infection is Streptococcus pyogenes. Rapid Antigen Diagnostic Test (RADT) facilitates the rapid identification and consequently prompt treatment of patients, prevents complications, and also reduces the risk of spread of Group A Streptococcus (GAS). The main objective of this study was to assess the diagnostic value of a rapid streptococcal antigen detection test in patients with sore throat. METHODS: A cross-sectional descriptive study was carried out from January to April 2011 on patients aged 3 to 72 years consulting for pharyngitis or sore throat at the paediatric and Ear, Nose and Throat units of the University Teaching Hospital Yaounde and the Central Hospital Yaounde. Two throat swabs were collected per patient. One was used for the rapid test and the other for standard bacteriological analysis. RESULTS: The prevalence of GAS in the study population was 22.5%. Out of the 71 samples collected, the RADT detected group A streptococcal antigens in 12 of 16 positive cultures giving a sensitivity of 75%. The specificity of the rapid test was 96%, with positive predictive value of 85.7%, and negative predictive value of 93% respectively. CONCLUSION: Rapid test may have an additional value in the management of patients with high risk of having GAS infection. However, tests with a higher sensitivity are needed for accurate and reliable results for early diagnosis of patients with sore throat caused by GAS. PMID- 27386018 TI - PTCH-1 and MDM2 expression in ameloblastoma from a West African sub-population: implication for chemotherapeutics. AB - INTRODUCTION: Ameloblastoma is a slow growing, painless odontogenic swelling which can attain sizes that result in severe deformities of the craniofacial complex. It is the most commonly encountered odontogenic tumor in Nigeria. Surgical intervention is currently the method of treatment; however identification of altered molecular pathways may inform chemotherapeutic potential. The Protein Patched homolog 1 (PTCH-1) is overexpressed in ameloblastoma. Also, mutation in the MDM2 gene can reduce the tumor suppressor function of p53 and promote ameloblastoma growth. No study however has characterized the molecular profile of African cases of ameloblastoma with a view to developing chemotherapeutic alternatives. The objective was to characterize the PTCH-1 genetic profile of Ameloblastoma in Nigerian patients as a first step in investigating its potential for chemotherapeutic intervention. METHODS: Twenty eight FFPE blocks of ameloblastoma cases from Nigerian patients were prepared for antibody processing to PTCH-1 (Polyclonal Anti-PTCH antibody ab39266) and MDM2 (Monoclonal Anti-MDM2 antibody (2A10) ab16895). Cytoplasmic brown staining was considered as positive for PTCH while nuclear staining was positive for MDM2. RESULTS: Moderate and strong expressions for PTCH in ameloblast and stellate reticulum were 78.6% and 60.7% respectively. Only 3 (10.7%) cases expressed MDM2. CONCLUSION: The importance of our study is that it supports, in theory, anti PTCH/SHH chemotherapeutics for Nigerian ameloblastoma cases and also infers the possible additional use of anti-p53 agents. PMID- 27386019 TI - [Dehydration revealing 3betahydroxysteroid dehydrogenase deficiency: report of a case]. PMID- 27386021 TI - [Schamberg purpura]. PMID- 27386020 TI - Knowledge, attitudes and practices of contraception by HIV positive women followed in a Cameroon region with high illiteracy rate: a cross sectional study. AB - INTRODUCTION: To evaluate the knowledge, attitude and practices of contraception by HIV positive women. METHODS: This cross-sectional descriptive study was carried out in the Maroua Regional Hospital (Cameroon) from September 1(st), 2012 to February 28(th), 2013. All HIV positive women aged between 15 and 49 years who were received in the HIV clinic were recruited. The variables recorded included maternal age, number of living children, marital status, religion, the educational level, and the use of antiretroviral treatment (HAART), the knowledge, attitude and practice of contraception. Analyses were done using SPSS 18.0. Fisher exact test was used for comparison. The level of significance was P < 0.05. RESULTS: A total of 200 HIV positive women were recruited and 98% knew at least one method of contraception The need of a contraceptive method was present in 84% of HIV positive women, as soon as the women were >= 30 years (OR 2.6, 95%CI 1.3-4.9), on HAART (OR 2.8, 95%CI 0.8-9.2), divorced (OR 1.7, 95%CI 0.8 3.7), had >= 3 living children (OR 1.2, 95%CI 0.6-2.4) and when the women were educated (OR 1.2, 95%CI 0.6-2.4). The rate of condom use was 50.7%. CONCLUSION: The knowledge of contraception as well as the contraception need among HIV positive women was high in this region despite high illiteracy rate. Therefore, all contraceptive methods should be made available to these women. Towards these women and their partner(s), more emphasis should be made on the systematic condom use even when using other contraceptive methods (dual protection). PMID- 27386022 TI - Noninvasive predictors of presence and grade of esophageal varices in viral cirrhotic patients. AB - Predicting the presence and the grade of varices by non-invasive methods is likely to predict the need for prophylactic beta blockers or endoscopic variceal ligation. The factors related to the presence of varices are not well-defined. Therefore, the present study has been undertaken to determine the appropriateness of the various factors in predicting the existence and also the grade of esophageal varices. Patients with diagnosis of liver cirrhosis due to hepatitis C or B were included in a retrospective study between January 2001 and January 2010. All the patients underwent detailed clinical evaluation, appropriate investigations, imaging studies (ultrasound with Doppler) and endoscopy at our center. Five variables considered relevant to the presence and grade of varices were tested using univariate and multivariate analysis (logistic regression). Three hundred and seventy two patients with viral liver cirrhosis were included, with 192 (51.6%) males. Platelet count and abundance of ascites were significantly associated with the presence of esophageal varices. However, abundance of ascites, prothrombin time, diameter of the spleen and portal vein were significantly associated with a large varice. In multivariate analysis, platelet count inferior to 100000 was associated with presence of varices (p = 0.04) and only abundance of ascites was associated with large varice. Low Platelet count (< or equal 100000) is associated with the presence of varices in viral cirrhotic patients and abundance of ascites is correlated with the presence of large varices. PMID- 27386023 TI - [A bullous tattoo]. PMID- 27386024 TI - [Bacteriological profile of diabetic foot and its impact on the choice of antibiotics]. PMID- 27386025 TI - [Panfaciale fracture: a therapeutic challenge: about a case report and review of literature]. PMID- 27386026 TI - [Intestinal cystic pneumatosis secondary to a peptic ulcer: report of three cases]. PMID- 27386027 TI - Health care utilization among rural women of child-bearing age: a Nigerian experience. AB - INTRODUCTION: Despite the availability of primary health care services in virtually every community and village in Nigeria, clients travel long distances to reach secondary and tertiary health care institutions. Against this backdrop, the researcher sought to find the factors that influence choice of health institutions among pregnant women. METHODS: A descriptive study was carried out across three levels of health care institutions with a total sample size of 160 clients who were randomly selected. A thoroughly validated 45- item questionnaire was used to explore clients' perceptions about what factors influence where they access health care services. RESULTS: Major findings revealed that level of education, proximity to place of residence, affordability and quality of services rendered, spousal and significant other's influences were active determinants of choice for health institutions among pregnant women in Nigeria. CONCLUSION: This study elicited information on why some types of institutions were preferred. The study has implications for community health nurses and policy makers on what should be done to make health institutions appropriately utilized by community in Nigeria. PMID- 27386028 TI - Primary squamous cell carcinoma of the breast: a case report and review of literature. AB - Primary squamous cell carcinoma is a well known malignancy of the skin and other organs composed of squamous cells, which are normally not found inside the breast. Therefore, a primary squamous cell carcinoma of the breast is an exceedingly uncommon phenomen and the management of this type of disease is still unclear. We report the case of a 43-year-old Moroccan woman, without significant medical history, presented an infected mass of 9 cm in the left breast associated with ipsilateral axillary lymphadenopathy. The mass's surgical biopsy revealed a triple negative primary squamous cell carcinoma of the breast. She underwent a neoadjuvant chemotherapy using 5 Fluoro-Uracil and platinum. After three courses, she presented a contralateral breast progression and apparition of metastasis at D10. She received one course of a palliative chemotherapy based on weekly paclitaxel stopped because of her peformans status deterioration. She died 7 months after her admission. PMID- 27386029 TI - Severe ocular sequelae of congenital toxoplasmosis: huge macular scar. AB - Retinochoroiditis is the most common ocular manifestation of congenital toxoplasmosis, but other associated ophthalmological pathologies can also occur. Ophthalmologists are rarely able to distinguish between toxoplasmic retinochoroiditis due to infection acquired before or after birth, unless other clinical or serological indications are present. This article reports a case of a 3-year-old boy with abnormalities suggestive of congenital toxoplasmosis. The clinical and complementary examinations are discussed. The education of pregnant women is crucial for the prevention of congenital toxoplasmosis. Awareness of antenatal and postnatal presenting signs and symptoms is important for clinicians, because early diagnosis and treatment may minimize sequelae. Untreated, the majority of affected infants will develop chorioretinitis, deafness and/or neurological symptoms. PMID- 27386030 TI - [Bilateral primitive non-Hodgkin Lymphoma of the breast: about a case]. PMID- 27386031 TI - Fertility desires, unmet need for family planning, and unwanted pregnancies among HIV-infected women in care in Kinshasa, DR Congo. AB - INTRODUCTION: We assessed the fertility desires, utilization of family planning (FP) methods, and incidence of pregnancies among HIV-infected women receiving care in an HIV clinic with an onsite FP services in Kinshasa, Democratic Republic of Congo. METHODS: Between November 2011 and May 2012, all HIV-infected women who attended a routine visit at the clinic were interviewed about their fertility desires and utilization of contraceptive methods using a structured questionnaire. Routine follow-up visit data were used to identify pregnancies recorded between the interview and June 2013. RESULTS: Overall, of the 699 HIV infected women interviewed. 249 (35.7%) reported not wanting another child. Of the 499 (72.2%) participants who were sexually active at the time of interview, 177 (35.5%) were using an effective contraceptive method, including 70 (14.0%) women who reported using condoms consistently and 104 (20.8%) who were using injectable contraception. Overall, 88 (17.6%) sexually active participants who did not want another child were not using an effective FP method, and thus are considered to have had unmet need. During the median follow-up time of 22.2 (IQR: 20.2, 23.6) months, among all women interviewed, 96 (14.1%) became newly pregnant [pregnancy rate 9.3 (95%CI: 7.6, 11.4) per 100 women-years] including 21 (8.7%) among women who initially reported not wanting another child [unwanted pregnancy rate 5.8 (95%CI: 3.6, 9.3) per 100 women-years]. CONCLUSION: The persistence of relatively high unmet need among women receiving HIV care in a clinic with onsite FP services suggests the existence of barriers that must be identified and addressed. PMID- 27386032 TI - Changes in potassium and sodium concentrations in stored blood. AB - Potassium is the principal intracellular cation with sodium being the principal extracellular cation. Maintenance of the distribution of potassium and sodium between the intracellular and the extracellular compartments relies on several homeostatic mechanisms. This study analysed the effect of blood storage on the concentrations of potassium and sodium in stored blood and also determine any variations that may exist in their concentrations. 50 mls of blood was sampled each from 28 units of evenly mixed donated blood in citrate phosphate dextrose adenine (CPDA-1) bags immediately after donation into satellite bag and stored at 4oC. Potassium and sodium concentration determinations were done on each of the 28 samples on day 0 (before blood was initially stored in the fridge), day 5, day 10, day 15 and day 20 of storage using the Roche 9180 ISE Electrolyte Analyser (Hoffmann-La Roche Ltd, Switzerland). data analysis showed significant changes in the potassium and sodium concentrations with a continuous rise in potassium and a continuous fall in sodium. A daily change of 0.59 mmol/l and 0.50 mmol/l was observed in the potassium and sodium concentrations respectively. We showed steady but increased daily concentrations of potassium and decrease concentrations of sodium in blood stored over time at 4oC. PMID- 27386034 TI - Ossified chronic epidural hematoma of the posterior fossa. PMID- 27386033 TI - Supportive supervision for medicines management in government health facilities in Kiambu County, Kenya: a health workers' perspective. AB - INTRODUCTION: Effective supportive supervision is widely recognized as essential for optimal management of medicines in government health facilities and also in contributing towards improved access and utilization of health services. This study sought to examine the extent supportive supervision for medicines management in government health facilities from a health worker perspective. METHODS: A cross-sectional study was done targeting health workers managing medicines in government health facilities in Kiambu County. One hundred and thirty eight respondents took part in the study which explored the quality of supportive supervision from a health worker's perspective, and also examined the factors influencing their contentment with the level of supervision received. A statistical analysis was done using SPSS 21 and Excel 2013. RESULTS: Supervisory visits from all levels of health management were not regularly done, standard checklists were not routinely used, and action plans irregularly developed and followed up. Only 54 (38.6%) respondents were satisfied with the levels of supportive supervision that they received, with satisfaction significantly differing across the professional cadres, chi (2) (12, n = 138) = 29.762, p = .003; across the different tiers of health facilities, r s (138) = 0.341, p < .001; and with the education levels of the respondents, r s (138) = 0.381, p < .001. CONCLUSION: The study concluded that supportive supervision for medicines management that government health facilities received was still inadequate, and health workers were dissatisfied with the level of supervision that they received. The study recommends a review of the support supervision policy at the county level to address the unearthed inefficiencies and improve supervision for medicines management in government health facilities. PMID- 27386035 TI - Pregnancy related breast diseases in a developing African country: Initial Sonographic Evaluation. AB - Benign diseases are more common than malignant diseases in pregnant and lactating women. Fibroadenomas are the most commonly identified benign breast tumour in pregnant and lactating women. Pregnancy related breast cancer is defined as breast cancer that occurs during pregnancy or within 1 year of delivery. Its incidence is estimated at 1 in 3000 to 1 in 10 000 pregnancies. Several reproductive factors like age at menarche, age at menopause, age at full-term pregnancy, parity, age at any birth and spacing of pregnancies, breast feeding, characteristics of the menstrual cycle, infertility, spontaneous and induced abortions, characteristics of the menstrual cycle and infertility are some of the factors that have been incriminated as risk factors for breast cancer. We sought to describe the predominant breast pattern, sonographic array of pregnancy related breast diseases in women referred to the breast imaging unit in the department of Radiology at the University College Hospital, Ibadan south west Nigeria. Socio-demographic characteristics in these women were also evaluated. Archived images were reviewed and documented and data was analysed with SPSS version 17 and presented with descriptives. In this descriptive study, we retrospectively retrieved the sonomammographic records of 21 women (pregnant or lactating) referred to and imaged in the department of radiology, University college hospital Ibadan, between 2006 and 2013. Diagnostic breast sonograms performed by MO and ATS; Consultant radiologists with 7-10 years' experience utilized a 7-10 MHz transducer of the General electric GE Logiq P5 machine for the scans. Twenty-one women with ages between 22-42 years (Mean 31.4 +/- 5.4 SD) pregnant or lactating were referred to the radiology department for sonomammographic evaluation. Majority of the women were in the 3rd decade. Referral was mainly (11) by family Physicians from the general outpatient clinic, 5 were self-referred, 2 from radiotherapy department, 2 from obstetrics and gynaecology department and 1 from the surgical outpatient clinic. Nineteen (89.5%) were lactating and breastfeeding while 2 (10.5%) were pregnant. Nipple discharge (89.5%) was the predominant presenting complaint in the study. They were all married with the majority attaining menarche at age 14.6 +/- 2.1 SD years. Most of the women were multi-parous 17(89.5%) and possessed higher level of Education 17 (81.0%). Twenty (96.0%) women had no previous breast disease while only 1 (4.0%) woman had a positive family history of breast cancer. They weighed between 44-102 kg (mean 69.84 kg +/- 15.33 SD). Their mean height was 159.8 cm. Waist hip ratio was between 0.69-0.93 (Mean 0.83). The heterogeneous fibroglandular pattern was predominant in 15 (71.4%) women. Final BIRADS assessment of 2 was most frequent (11/21) 52.4% while 19.0% were assigned to BIRADS categories 0 and 1 (4/21). Histological diagnosis of Invasive ductal carcinoma was made in the 3 women with final BIRADS of 5 breast diseases found in most pregnant and lactating women were benign. It is important to note that malignant breast lesions can also occur in this group of women who may assume that the changes noted in their breast are due to lactation. PMID- 27386036 TI - Adenoid cystic carcinoma of the trachea: a clinico-pathological analysis. AB - Primary malignant tracheal tumors are not common and adenoid cystic carcinoma (ACC) of trachea is very rare. The diagnosis is often delayed due to the atypical symptoms. We report an extremely rare case of ACC of proximal trachea, in a 55 year-old female who presented with a 12 month history of progressive dyspnea. Laryngoscopy and computed tomography revealed a broad-based polypoidal mass arising from posterior wall of the proximal trachea. Biopsy confirmed the diagnosis of ACC. The patient underwent a complete surgical resection and post operative radiotherapy. Six months follow-up of the patient did not reveal local recurrence or distant metastases. The literature of tracheal ACC is reviewed. PMID- 27386038 TI - Training the trainers in emergency medicine: an advanced trauma training course in Rwanda's medical simulation center. PMID- 27386037 TI - Hematologic features among anemic Cameroonian pregnant women: a cross sectional study. AB - INTRODUCTION: Iron deficiency anemia is the leading cause of anemia worldwide. It may also be the leading cause of anemia in pregnancy, although this has not yet been demonstrated in our country. The aim of the study was to describe hematologic features of Cameroonian anemic pregnant women. METHODS: This cross sectional analytical study was carried out in the maternity of the Yaounde University Teaching Hospital, Cameroon, from March 1(st), 2011 to February 28(th), 2013. Two hundred women with singleton pregnancies and Hb concentration at booking <10 g/dl were recruited. Main variables recorded were maternal age, parity, marital status, gestational age, Hb concentration, blood group, Hb electrophoresis, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), pack cell volume (PCV). Data were analyzed using SPSS 18.0. P<0.05 was considered statistically significant. RESULTS: Figures for 110 women (55%) showed microcytosis, hypochromia was observed in 122 (61%) women and megaloblastic anemia in eight women (4%). Thrombopenia was observed in 16 women (8%) and thrombocytosis in six women (3%). Anemia was microcytic hypochromic in 110 women (55%), megaloblastic in eight women (4%), normocytic hypochromic in 12 women (6%), and normocytic normochromic in 70 women (35%). CONCLUSION: Hematologic features of Cameroonian anemic pregnant women showed that although iron deficiency anemia is the leading cause of anemia, megaloblastic anemia is also present in our environment. A normal hematologic feature in more than the third of women shows that the cause of anemia is not always nutritional. PMID- 27386039 TI - Experiences, perceptions and preferences of mothers towards childhood immunization reminder/recall in Ibadan, Nigeria: a cross-sectional study. AB - INTRODUCTION: Immunization reminder/recall system is proven as one of the effective ways of improving immunization rates. Prior to the development and implementation of an immunization reminder/recall system intervention, we explored the experiences, preferences and perceptions towards childhood immunization reminder/recall among 614 mothers of infants in Ibadan, Nigeria. METHODS: A cross-sectional health facility-based survey utilizing a semi structured questionnaire was conducted in four Primary Health Care centers. Descriptive statistics were computed using SPSS. Logistic models were used to investigate the relationships with specific outcomes. RESULTS: Only 3.9% had ever heard of immunization reminder/recall and 1.5% had ever received one. However, 97.9% were willing to record their cellphone numbers in the clinics for immunization reminder/recall and 95.1% were willing to receive. Their preferred communication modes were cell phone calls (57.6%) or text messages/SMS (35.6%). Only 2.2% preferred home-visits and 0.4%, e-mails. About 4% were not willing to receive any form of immunization reminder/recall. Mothers with post-secondary education were more likely to prefer SMS than other mothers (OR 2.3, 95% CI 1.7 3.3, p. CONCLUSION: This study provided critical baseline data for designing a reminder/recall intervention for routine childhood immunization in the study communities. The findings may serve as a guide for public health professionals in designing reminder/recall strategies to improve childhood immunization. PMID- 27386041 TI - Eosinophilic bioactivities in severe asthma. AB - Asthma is clearly related to airway or blood eosinophilia, and asthmatics with significant eosinophilia are at higher risk for more severe disease. Eosinophils actively contribute to innate and adaptive immune responses and inflammatory cascades through the production and release of diverse chemokines, cytokines, lipid mediators and other growth factors. Eosinophils may persist in the blood and airways despite guidelines-based treatment. This review details eosinophil effector mechanisms, surface markers, and clinical outcomes associated with eosinophilia and asthma severity. There is interest in the potential of eosinophils or their products to predict treatment response with biotherapeutics and their usefulness as biomarkers. This is important as monoclonal antibodies are targeting cytokines and eosinophils in different lung environments for treating severe asthma. Identifying disease state-specific eosinophil biomarkers would help to refine these strategies and choose likely responders to biotherapeutics. PMID- 27386042 TI - Defining Field Cancerization of the Skin Using Noninvasive Optical Coherence Tomography Imaging to Detect and Monitor Actinic Keratosis in Ingenol Mebutate 0.015%- Treated Patients. AB - OBJECTIVE: The objective of this study was to assess the ability of optical coherence tomography to detect clinical and subclinical actinic keratoses confirmed by histopathology. The efficacy of ingenol mebutate treatment of actinic keratosis was also evaluated using optical coherence tomography, and correlation of treatment efficacy with severity of local skin reactions was determined. DESIGN: Single-arm, open-label, split-face study. SETTING: Hospital outpatient clinic. PARTICIPANTS: Male subjects (N=30) with seven actinic keratoses. MEASUREMENTS: A suspected actinic keratosis and the normal-appearing, perilesional skin were imaged, biopsied for histopathologic analysis, and the results compared with the clinical and a blinded optical coherence tomography diagnosis. Treatment with ingenol mebutate gel 0.015% was randomly administered to three clinically suspected actinic keratoses and the perilesional skin; three additional, suspected actinic keratoses lesions and perilesional areas were left untreated. Clinical and optical coherence tomography images were obtained for all lesions. Severity of local skin reactions was recorded to evaluate the relationship between local skin reaction and treatment effect. RESULTS: Optical coherence tomography analysis had a 100-percent (28/28) correlation with the clinical diagnosis of actinic keratosis and detected 16 of 22 (73%) histopathologically confirmed subclinical lesions from perilesional skin sites. By optical coherence tomography assessment, the clearance rate for clinically observed lesions was 76 percent for ingenol mebutate-treated areas versus 11 percent for untreated areas; the clearance rate for treated subclinical lesions was 88 percent versus 43 percent for untreated areas. Clearance rates did not vary with the severity of the local response. CONCLUSION: Optical coherence tomography is effective at detecting clinical and subclinical actinic keratoses and monitoring their response to treatment. PMID- 27386044 TI - Use of Polypodium leucotomas Extract in Clinical Practice: A Primer for the Clinician. AB - Polypodium leucotomas extract is a natural product derived from a tropical fern that is available as an over-the-counter product in the United States and several other countries. A designated brand of oral Polypodium leucotomas extract has been shown in several research studies to exhibit a variety of antioxidant and photoprotective properties. Clinical research with this same formulation of Polypodium leucotomas extract has demonstrated multiple potential therapeutic applications. This article provides a thorough overview of research completed with Polypodium leucotomas extract and outlines suggested approaches for clinical use. PMID- 27386045 TI - The Incidence of Hypertrophic Scarring and Keloid Formation Following Laser Tattoo Removal with a Quality-switched Nd:YAG Laser. AB - BACKGROUND: Laser tattoo removal using quality switched technology is widely accepted as the standard of care. Determining the risk of hypertrophic scarring and keloid formation more precisely delineates the safety of this procedure and improves patient education regarding the risk of scarring. OBJECTIVE: To investigate the incidence of hypertrophic scarring and keloids in a large patient population following treatment with a Q-switched neodymium-doped:yttrium-aluminum garnet laser. DESIGN: In November 2012, after a single Institutional Review Board approved retrospective chart review, 1,041 charts demonstrating greater than five treatment sessions were analyzed. All patients in the current retrospective study were treated under one study protocol. RESULTS: An overall incidence of 0.28 percent (3/1,041) of patients receiving a minimum of five laser tattoo treatments with a Q-switched neodymium-doped:yttrium-aluminum-garnet laser developed clinical evidence of hypertrophic scarring. None of the 1,041 patients in this study developed keloid scars. CONCLUSION: With the Q-switched neodymium doped:yttrium-aluminum-garnet laser utilizing accurate, protocol-based settings, the incidence of hypertrophic scarring following laser tattoo removal treatments was 0.28 percent (3/1,041) and the incidence of keloid scarring was 0.00 percent (0/1,041). PMID- 27386043 TI - Basal Cell Carcinoma: A Comprehensive Review of Existing and Emerging Nonsurgical Therapies. AB - Basal cell carcinoma is the most commonly occurring cancer in the world and overall incidence is still on the rise. While typically a slow-growing tumor for which metastases is rare, basal cell carcinoma can be locally destructive and disfiguring. Given the vast prevalence of this disease, there is a significant overall burden on patient well-being and quality of life. The current mainstay of basal cell carcinoma treatment involves surgical modalities, such as electrodessication and curettage, excision, cryosurgery, and Mohs micrographic surgery. Such methods are typically reserved for localized basal cell carcinoma and offer high five-year cure rates, but come with the risk of functional impairment, disfigurement, and scarring. Here, the authors review the evidence and indications for nonsurgical treatment modalities in cases where surgery is impractical, contraindicated, or simply not desired by the patient. PMID- 27386046 TI - Silicone Granulomas, a Growing Problem? AB - The formation of granulomas is known to be a possible adverse effect of liquid silicone administration, used for soft tissue augmentation. Its plumping effects provide enhancement of certain body parts, such as the lips, hips, and buttocks. The desire for enhancement, perhaps influenced by popular culture and an unrealistic standard of beauty, leads individuals to seek silicone injections. There is a growing population of women and men receiving injections by unlicensed, unskilled "practitioners" not related to the healthcare profession. Complications under such circumstances are not uncommon, particularly the emergence of silicone granulomas, and the authors' medical center has seen an increase in such cases. In this case report, the authors illustrate a young patient with significant complications from her silicone injections, review current therapies for silicone granulomas, and discuss this growing medical problem. PMID- 27386047 TI - Status Report from the Scientific Panel on Antibiotic Use in Dermatology of the American Acne and Rosacea Society: Part 3: Current Perspectives on Skin and Soft Tissue Infections with Emphasis on Methicillin-resistant Staphylococcus aureus, Commonly Encountered Scenarios when Antibiotic Use May Not Be Needed, and Concluding Remarks on Rational Use of Antibiotics in Dermatology. AB - In this third article of the three-part series, management of skin and soft tissue infections is reviewed with emphasis on new information on methicillin resistant Staphylococcus aureus. Due to changes in the evolution of methicillin resistant Staphylococcus aureus clones, previous distinctions between healthcare acquired methicillin-resistant Staphylococcus aureus and community-acquired methicillin-resistant Staphylococcus aureus are currently much less clinically relevant. Many nosocomial cases of methicillin-resistant Staphylococcus aureus infection are now caused by community-acquired methicillin-resistant Staphylococcus aureus, with changing patterns of antibiotic susceptibility and resistance. Also reviewed are clinical scenarios where antibiotics may not be needed and suggestions for optimal use of antibiotic therapy for dermatologie conditions, including recommendations on perioperative antibiotic use. PMID- 27386048 TI - Staged Excision for Lentigo Maligna and Lentigo Maligna Melanoma: Analysis of Surgical Margins and Long-term Recurrence in 68 Cases from a Single Practice. AB - INTRODUCTION: Lentigo maligna is a form of in situ melanoma that occurs commonly on sun-exposed skin of middle-aged to elderly adults. Margin-control surgery offers the highest cure rate for lentigo maligna/lentigo maligna melanoma. MATERIALS AND METHODS: Charts from the authors' private office from the 20-year period from January 1986 to December 2005 were reviewed to identify patients with histologically confirmed lentigo maligna or lentigo maligna melanoma treated by staged excision. RESULTS: Sixty-eight patients (39 men, 29 women; mean age at diagnosis 67.4+/-10.2 years, range 48-87 years) with 68 tumors were treated in the authors' office for lentigo maligna (58) or lentigo maligna melanoma (10) between January 1986 and December 2005. After excision, patients were followed clinically for a minimum of three years. The mean follow-up duration was 138 months (median 139 months; range 37-330 months). The overall margin for tumor clearance was 7.0+/-0.55mm with a recurrence rate of 5.9 percent. LIMITATIONS: The limitations of this study include the retrospective nature of the authors' review, and data collected from a single, private practice setting. CONCLUSION: The authors' findings support staged excision as an effective method of treating lentigo maligna and lentigo maligna melanoma, offering a high cure rate while maximally preserving normal tissue. PMID- 27386049 TI - A Six-week Low-level Laser Therapy Protocol is Effective for Reducing Waist, Hip, Thigh, and Upper Abdomen Circumference. AB - OBJECTIVE: The efficacy of low-level laser therapy for noninvasive body contouring has been previously demonstrated in clinical trials leading to its market clearance. Subjects achieved these beneficial effects following three weekly low-level laser therapy treatments for two weeks. The objective of this study was to determine if the same aesthetic benefit can be achieved following one weekly low-level laser therapy treatment for six weeks. SETTING: Two private dermatology practices. PARTICIPANTS: Healthy adults with a body mass index of 25 to 40kg/m(2) (N=54). MEASUREMENTS: Subjects underwent one weekly low-level laser therapy procedure for six consecutive weeks using a device consisting of six 17mW, 635nm red diodes. Waist, hip, thigh, and upper abdomen circumference were measured weekly. Study success criteria was a 4.5-inch mean decrease in combined body circumference. RESULTS: The mean decrease in combined circumference reduction at six weeks was 5.4 inches (p<0.001), and most subjects (72.2%) achieved a >=4.5-inch decrease. Most subjects (81.0%) were Satisfied (27%) or Very Satisfied (54%) with the aesthetic results they achieved. There were no adverse events. CONCLUSION: One weekly low-level laser therapy treatment for six weeks is clinically effective for reducing waist, hip, thigh, and upper abdomen circumference and may be more effective than the previous two-week treatment protocol. ClinicalTrials.gov Identifier: NCT02109107. PMID- 27386040 TI - Particularities of allergy in the Tropics. AB - Allergic diseases are distributed worldwide and their risk factors and triggers vary according to geographical and socioeconomic conditions. Allergies are frequent in the Tropics but aspects of their prevalence, natural history, risk factors, sensitizers and triggers are not well defined and some are expected to be different from those in temperate zone countries. The aim of this review is to investigate if allergic diseases in the Tropics have particularities that deserve special attention for research and clinical practice. Such information will help to form a better understanding of the pathogenesis, diagnosis and management of allergic diseases in the Tropics. As expected, we found particularities in the Tropics that merit further study because they strongly affect the natural history of common allergic diseases; most of them related to climate conditions that favor permanent exposure to mite allergens, helminth infections and stinging insects. In addition, we detected several unmet needs in important areas which should be investigated and solved by collaborative efforts led by the emergent research groups on allergy from tropical countries. PMID- 27386050 TI - Psoriasis and Associated Psychiatric Disorders: A Systematic Review on Etiopathogenesis and Clinical Correlation. AB - INTRODUCTION AND OBJECTIVE: Psoriasis is a chronic skin disease with a high impact on self-esteem and patients' health-related quality of life. In the last decades some studies have pointed out mental disorders associated with psoriasis and the etiopathogenic mechanisms behind that co-existence. This work compiles psychopathology associated with psoriasis and further analyzes the etiopathogenesis of psoriasis and mental disorders. METHODS: A systematic review of the literature was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and using the "5S" levels of organization of evidence from healthcare research, as previously described. RESULTS: Psoriasis is linked with many mental disorders, both in the psychotic and neurotic sprectrum. Chronic stress diminishes hypothalamic-pituitary-adrenal axis and upregulates sympathetic-adrenal-medullary responses, stimulating pro inflammatory cytokines. Then, it maintains and exacerbates psoriasis and some of its mental disorders. High levels of pro-inflammatory cytokines connect psoriasis, psychiatric conditions, and other comorbidities of psoriasis (such as atherosclerosis) within a vicious cycle. Furthermore, the etiopathogenesis of the link between each psychiatric comorbidity and psoriasis has its own subtleties, including the cooccurrence of other comorbidities, the parts of the body affected by psoriasis, treatments, and biological and psychosocial factors. CONCLUSION: The study of psychopathology can amplify our understanding about the etiopathogenesis of psoriasis and associated mental disorders. Patients would benefit from a psychodermatologic approach. The adequate treatment should take into account the mental disorders associated with psoriasis as well as the circumstances under which they occur. PMID- 27386051 TI - Finasteride in Hidradenitis Suppurativa: A "Male" Therapy for a Predominantly "Female" Disease. AB - OBJECTIVE: Hidradenitis suppurativa is associated with obesity and metabolic syndrome, and a hormonal component has been implicated. Finasteride is an anti androgenic agent used for benign prostatic hypertrophy, androgenic alopecia, and, in females, hirsutism. Finasteride is an inhibitor of type II5 alpha-reductase that reduces dihydrotestosterone levels and appears to alter end-organ sensitivity of the folliculopilosebaceous unit. The objective is to review the use of finasteride for hidradenitis suppurativa. DESIGN: Review of the literature. SETTING: Clinical treatment of patients with hidradenitis suppurativa. Measurement/participants: Five publications described the use for hidradenitis suppurativa. Four global case reports cited 13 individual patients, four male and nine female. Females included three adolescent patients and a child aged seven with precocious puberty. In the United States, finasteride in obese male adults was mentioned to be helpful. RESULTS: Oral finasteride, as monotherapy or additional therapy was utilized for advanced hidradenitis suppurativa. The outcomes were largely favorable, with complete resolution in three patients. A latency period was evident in a majority. Limited, or continuous use for up to six years, was detailed. Response to reintroduction was successful. A benign safety profile with excellent tolerability was described. Teratogenicity of finasteride was addressed and contraception advocated in female patients. Sexual adverse effects were not ascertained. CONCLUSION: In hidradenitis suppurativa, finasteride could be considered in adults of both sexes as well as in select female children and adolescents, particularly those with concurrent metabolic and hormonal alterations present. Finasteride provides another highly effective, durable, relatively safe, and inexpensive option in the treatment of hidradenitis suppurativa. PMID- 27386052 TI - Use of Kaolin-impregnated Gauze for Improvement of Intraoperative Hemostasis and Postoperative Wound Healing in Blepharoplasty. AB - PURPOSE: Kaolin is a mineral shown to be effective in controlling hemorrhage when combined with standard gauze and applied to wounds. This study investigates the application of kaolin to control intraoperative bleeding and promote wound healing in eyelid surgery. METHODS: This prospective, randomized, double-blind study recruited patients who underwent eyelid surgery. Following skin incision, kaolin-impregnated gauzewas placed in one eyelid wound bed and cotton gauze in the other, then removed. Distinct, individual areas of bleeding were recorded. Standardized photographs were obtained postoperatively on Day 1, 4, and 7. Photographs were graded for edema and ecchymosis by four blinded observers. Patients also completed a survey inquiring which side had more bruising, swelling, and pain at each return visit. RESULTS: A total of 46 patients completed the study. The number of intraoperative bleeding sites for kaolin versus plain gauze was not significantly different (p=0.96). Photographic grading by blinded observers did not identify any statistically significant differences in postoperative edema at any time point between lids. There was a statistically significant difference for ecchymosis at postoperative Day 4 (p=0.009) and Day 7 (p=0.016). Patient surveys did not show any difference in perceived edema, ecchymosis, or pain between lids. CONCLUSION: Intraoperative hemostasis was not affected by the use of kaolin-impregnated gauze. The effectiveness of kaolin in wound healing showed improved ecchymosis at Days 4 and 7 when assessed by blinded observers. Patients did not notice any improvement in postoperative edema, ecchymosis, or pain. PMID- 27386053 TI - Nodular Scleroderma Revisited: Systemic Sclerosis Presenting as Annular Keloidal Sclerotic Plaques. AB - BACKGROUND: Nodular scleroderma, also known as keloidal scleroderma, is a rare variant of systemic sclerosis. PURPOSE: The clinical features, pathologic findings and postulated pathogenesis of nodular scleroderma are discussed. METHODS: A woman with previously undiagnosed systemic sclerosis who presented with nodular scleroderma is described. Using the PubMed database, a literature search was performed on keloidal scleroderma, nodular scleroderma, and systemic sclerosis. RESULTS: Nodular scleroderma is characterized by firm plaques or nodules, which can mimic a keloid, that are typically located on the anterior orposterior upper trunk and the arms; they show pathologic changes of scleroderma, keloid, or hypertrophic scar. Akeloidal response of inflamed skin that is involved in an active fibrotic process inherent to systemic sclerosis, in individuals who are genetically predisposed to keloid formation, is the hypothesized pathogenesis. CONCLUSION: Nodular scleroderma is rare. The authors' patient presented with diarrhea, dysphagia, fatigue, Raynaud's phenomenon, shortness of breath, and annular keloidal plaques of morphea whose biopsy showed features of hypertrophic scar; additional studies confirmed the diagnosis of the nodular scleroderma variant of systemic sclerosis. The possibility of systemic sclerosis should be entertained in patients who present with nodularor keloidal plaques that morphologically resemble morphea and have histologic findings of a scar or a keloid-especially if there are associated symptoms suggestive for systemic sclerosis. PMID- 27386054 TI - Validation of disease states in schizophrenia: comparison of cluster analysis between US and European populations. AB - BACKGROUND: There is controversy as to whether use of statistical clustering methods to identify common disease patterns in schizophrenia identifies patterns generalizable across countries. OBJECTIVE: The goal of this study was to compare disease states identified in a published study (Mohr/Lenert, 2004) considering US patients to disease states in a European cohort (EuroSC) considering English, French, and German patients. METHODS: Using methods paralleling those in Mohr/Lenert, we conducted a principal component analysis (PCA) on Positive and Negative Syndrome Scale items in the EuroSC data set (n=1,208), followed by k means cluster analyses and a search for an optimal k. The optimal model structure was compared to Mohr/Lenert by assigning discrete severity levels to each cluster in each factor based on the cluster center. A harmonized model was created and patients were assigned to health states using both approaches; agreement rates in state assignment were then calculated. RESULTS: Five factors accounting for 56% of total variance were obtained from PCA. These factors corresponded to positive symptoms (Factor 1), negative symptoms (Factor 2), cognitive impairment (Factor 3), hostility/aggression (Factor 4), and mood disorder (Factor 5) (as in Mohr/Lenert). The optimal number of cluster states was six. The kappa statistic (95% confidence interval) for agreement in state assignment was 0.686 (0.670 0.703). CONCLUSION: The patterns of schizophrenia effects identified using clustering in two different data sets were reasonably similar. Results suggest the Mohr/Lenert health state model is potentially generalizable to other populations. PMID- 27386055 TI - Efficacy and safety of conventional long acting beta2- agonists: systematic review and meta-analysis. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is usually considered one of the leading causes of death worldwide, so finding proper therapeutic strategies for this disease is of high importance. In this meta-analysis, we reviewed the existing literature on the efficacy and safety of conventional long acting beta agonists (LABAs) in COPD patients. METHODS: We searched MEDLINE and Google scholar to identify relevant articles. We limited data to double-blinded randomized controlled trials (RCTs). Data of 14, 832 COPD subjects including 7540 patients under a beta2 agonist (cases) and 7292 taking placebo (controls) retrieved from 20 randomized controlled trials and were enrolled into this meta analysis. Evaluated outcomes included overall mortality, exacerbations and tolerance to the drug. RESULTS: The analysis of survival showed no significant difference between those taking LABAs or placebo (relative risk (RR): 0.945, 95% confidence interval (CI): 0.821-1.088, P=0.432). Exacerbation rate, however, was significantly lower among the cases than among the controls (RR: 0.859, 95%CI: 0.800-0.922, p<0.001). Similar observation was detected in analyzing the rate of drug withdrawal in patients of the two groups with patients under placebo having significantly higher rate of drug discontinuation due to adverse events or disease symptoms (RR:0.821, 95% CI: 0.774-0.871; p<0.007). CONCLUSION: In conclusion, we found that the use of conventional LABA therapy in COPD patients is associated with a lower exacerbation rate of the disease as well as higher tolerance to the drug, but no survival advantage is expectable. Substitution of LABAs with new agents is recommended. PMID- 27386056 TI - Candida infections among neutropenic patients. AB - BACKGROUND: Systemic candidiasis is a major complication in neutropenic cancer patients undergoing treatment. Most systemic fungal infections emerge from endogenous microflora so the aim of the present study was to identify Candida species isolated from the different regions of body in neutropenic patients in compare with the control group. METHODS: A total of 309 neutropenic cancer patients and 584 patients without cancer (control group) entered in the study. Molecular identification of clinical isolates was performed by PCR-RFLP technique. RESULTS: Twenty-two out of 309 patients had candidiasis (7.1%). Male to female ratio was 1/1 and age ranged from 23 to 66 years. Colorectal cancer and acute myeloid leukemia (AML) were the most common cancers. Candida albicans was the most prevalent Candida species among neutropenic patients (50%) and control group (57.9%). Mortality rate in cancer patients was 13.6% in comparison with control group (5.2%). CONCLUSION: Since candidiasis is an important cause of morbidity and mortality in neutropenic patients, precise identification of Candida species by molecular techniques can be useful for the appropriate selection of antifungal drugs particularly in high risk patients. PMID- 27386057 TI - Addition of clidinium-C to the 14-day proton-pump inhibitor-based triple therapy for Helicobacter pylori eradication. AB - BACKGROUND: Triple therapy with a proton pump inhibitor and two antibiotics in Helicobacter pylori (HP) eradication is widely accepted, but this combination fails in a considerable number of cases. The aim of this study was to assess the effect of clidinium-C addition on HP eradication and to investigate the efficacy and safety of clidinium-C in prevention of drugs' side effects. METHODS: A total of 200 histopathologically confirmed HP positive peptic ulcer enrolled in this study which were randomly assigned to two treatment groups: OAC (20 mg omeprazole bid, 1000 mg amoxicillin bid and 500 mg clarithromycin bid) and OAC + clidinium C. The effect of treatment and adverse effects were compared 6 weeks after completion of treatment. A13C-urea breath test was performed to confirm HP eradication. RESULTS: A total of 184 patients (90 in group A and 94 in group B) completed the treatment protocols. HP eradication was achieved in 71.1% in OAC versus 72.3% in OCA+clidinium-C, (P=0.73). The frequencies of abdominal pain and stool abnormality, among the side effects recorded during the therapy period, were significantly lower in group B (OCA+clidinium-C) (P=0.01 and P=0.001, respectively). CONCLUSION: Addition of clidinium-C to OCA triple therapy decreases abdominal pain and frequency of stool abnormalities without affecting HP eradication rate. Based on these findings addition of clidinium-C may increase patient's compliance. PMID- 27386058 TI - Comparison study of QuantiFERON test with tuberculin skin testing to diagnose latent tuberculosis infection among nurses working in teaching hospitals of Ahvaz, Iran. AB - BACKGROUND: Prompt diagnosis and treatment of latent tuberculosis (TB) infection (LTBI) are needed to control TB. The aim of the study was to compare the performance of Quanti FERON-TB test (QFT) with conventional TST for the diagnosis of LTBI. METHODS: In this analytical - comparison study, we enrolled 87 nurses working in teaching hospitals in Ahvaz. All study subjects were tested by TST. TST results were interpreted as positive if induration was more than 10 mm. If the level of QFT after stimulation was equal or greater than 0.35 IU/ml, test was considered as positive. Data were analyzed with SPSS program. QFT results compared with induration in TST and its relation to all variables were investigated. RESULTS: The rate of LTB diagnosis by TST and QFT was 31% and 35.6%, respectively. There was no significant difference between TST and QFT in LTB diagnosis (P=0.62). Among the 56 subjects who were TST- negative, 14 cases (approximately 25%) were QFT- positive and 42 (75%) were QFT- negative. Among the 31 cases (35.6%) that had TST- positive, 13 (42%) were QFT-positive and 18 (58%) were QFT- negative. The overall percent agreement was 63.2% (k=0.139, P=0.69), discordance %=15.9-20.7, sensitivity= 41.5% and specificity=75.5%. CONCLUSION: Diagnostic value of QFT is similar to TST, when there is strong clinical and epidemiological evidence of LTB in a nurse with negative TST, adding QFT to diagnostic evaluation is associated with increased rate of LTB diagnosis. PMID- 27386059 TI - Altered plasma marker of oxidative DNA damage and total antioxidant capacity in patients with Alzheimer's disease. AB - BACKGROUND: Recent studies have shown that oxidative stress (OS) is the most important indicator in the pathogenesis of Alzheimer's disease (AD), but the results in previous studies are conflicting. This study aimed to assess the plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as DNA oxidative damage marker and total antioxidant capacity (TAC) in patients with AD versus control group. METHODS: Thirty patients with AD and 30 sex-and age-matched healthy subjects were studied. Diagnosis of AD was based on National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's disease and Related Disorders Association (NINCDS/ADRDA) criteria. Also for the patients, Mini-Mental State Examination (MMSE), computed tomography (CT) scan and brain magnetic resonance imaging (MRI) were done. Plasma levels of 8-OHdG and TAC were measured by competitive ELISA method and ferric reducing antioxidant power (FRAP) assay, respectively. RESULTS: Plasma levels of 8-OHdG was significantly higher in AD compared to control group (p<0.001), while the total antioxidant was significantly lower in patients compared to controls (p=0.002). The value of area under the ROC curve for 8-OHdG and TAC in discriminating AD from controls were 0.87 and 0.32, respectively. CONCLUSION: Our results indicate a link between oxidative stress and AD indicating a possible contributive role of these markers in the development of AD and as an indicator in the discrimination of AD from healthy controls. PMID- 27386060 TI - Influence of supplemental vitamin D on intensity of benign paroxysmal positional vertigo: A longitudinal clinical study. AB - BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is linked to vitamin D deficiency. This clinical trial aimed to determine the influence of vitamin D supplementation on intensity of BPPV. METHODS: The study population was selected consecutively and the diagnosis of BPPV was made by history and clinical examination and exclusion of other conditions. Intensity of BPVV was assessed based on VAS score (0-10). Serum 25-hydroxyvitamin D (25-OHD) was measured using ELISA method and levels < 20 ng/ml was considered a deficiency. All patients received rehabilitation treatment using Epley's maneuver one time per week for one month. Serum 25-OHD deficient patients were classified as treated and non treated groups (rehabilitation with or without 50.000 IU cholecalciferol weekly for two months).The results of treatment were compared with vitamin D sufficient group as control. All patients were followed-up for 6 months. RESULTS: After two months of treatment, in both vitamin D treated and non-treated groups the intensity of BPPV decreased significantly as compared with control (P=0.001 for both groups) but at endpoint, the intensity of BPPV aggravated and regressed to the baseline value in vitamin D deficient non-treated group (P=0.001) whereas, in vitamin D treated group, improvement of BPPV remained stable and unchanged over the study period. CONCLUSION: This study indicates that correction of vitamin D deficiency in BPPV provides additional benefit to rehabilitation therapy (Epley maneuver) regarding duration of improvement. These findings suggest serum 25-OHD measurement in recurrent BPPV. PMID- 27386061 TI - Efficiency and outcome of non-invasive versus invasive positive pressure ventilation therapy in respiratory failure due to chronic obstructive pulmonary disease. AB - BACKGROUND: Application noninvasive ventilation in the patients with exacerbation of chronic obstructive pulmonary disease (COPD) reduced mortality. This case control study was designed to compare efficiency and outcome of non-invasive (NIV) versus invasive positive pressure ventilation (IPPV) in respiratory failure due to COPD. METHODS: The patients were assigned to NIV or IPPV intermittantly.The clinical parameters, including RR (respiratory rate), BP (blood pressure), HR (heart rate) and PH, PaCO2, PaO2 before and 1, 4 and 24 h after treatment were measured. Demographic information such as age, sex, severity of disease based on APACHE score, length of stay and outcome were recorded. RESULTS: Fifty patients were enrolled in the NIV group and 50 patients in IPPV. The mean age was 70.5 in NIV and 63.9 in invasive ventilation group (p>0.05). In IPPV group, the average values of PH: PCO2: and PO2, were 7.22+/-0.11, 69.64 + 24.25: and 68.86+/-24.41 .In NIV, the respective values were 7.30+/-0.07, 83.94+/ 18.95, and 60.60+/-19.88. In NIV group, after 1, 4 and 24 h treatment, the clinical and ventilation parameters were stable. The mean APACHE score in was IPPV, 26.46+/-5.45 and in NIV was 12.26+/-5.54 (p<0.05). The average length of hospital stay in IPPV was 15.90+/-10 and in NIV 8.12+/-6.49 days (p<0.05). The total mortality in the NIV was 4 (8%) and in IPPV, 27 patients (54%) (p<0.05). CONCLUSION: This study indicates that using NIPPV is a useful therapeutic mode of treatment for respiratory failure with acceptable success rate and lower mortality. The application of NIPPV reduces hospital stay, intubation and its consequent complications. PMID- 27386062 TI - The acute lymphoblastic leukemia prognostic scoring whether it is possible by BCL 2, BAX gene promoter genotyping. AB - BACKGROUND: BCL-2 is the most important anti-apoptotic regulator and Bax is a pro apoptotic protein. The status of these parameters or the ration of BCL-2 to BAX is important in malignant cell fate as well as normal cells. METHODS: Sixty-two ALL patients and 62 healthy sex-and age-matched controls were studied. After genotyping, the promoter region of the BAX and BCL-2 genes by RFLP-PCR method the patients were classified in nine prognostic groups, after that, the overall survival ratio of each score was compared with others pair-wise or between groups. RESULTS: The frequencies of the AA, AC, CC alleles of the BCL-2 C-938A polymorphism in patient group were 33 (53.23%), 18 (29.03%), 11 (17.74%), and in the control group were 13 (21.0%), 27 (43.5%), 22 (35.5%), respectively (P=0.003). Also, the frequencies of AA, AG, GG alleles of the BAX G-248A SNP were 15 (24.2%), 24 (38.7%), 23 (37.1%) in ALL group and 13 (21.0%), 25 (40.3%), 24 (38.7%) (p>0.05) in the control group. The survival time estimation and ratio were significantly different between different SNPs in BCL-2 (P=0.002). CONCLUSION: These findings showed that the BCL-2 promoter region polymorphism is more reliable than BAX gene promoter polymorphism in any ALL scoring system. But the establishment of complete scoring system requires further more clinical and laboratory findings along with genetic polymorphisms is necessary. PMID- 27386063 TI - Multidrug resistance pattern of bacterial agents isolated from patient with chronic sinusitis. AB - BACKGROUND: Treatment of chronic sinusitis is complicated due to increase of antibiotic-resistant bacteria. The aim of this study was to determine the multidrug resistance (MDR) pattern of the bacteria causing chronic sinusitis in north of Iran. METHODS: This cross-sectional study was carried out on patients with chronic sinusitis. Bacterial susceptibility to antimicrobial agents was determined according to the CLSI 2013 standards. Double-disk synergy (DDS) test was performed for the detection of extended-spectrum beta-lactamase (ESBL) producing bacteria; also methicillin-resistant Staphylococcus (MRSA) strains were identified by MRSA screen agar. The MDR isolates were defined as resistant to 3 or more antibiotics. Data were analyzed using SPSS 17 software. Descriptive statistics was used to describe the features of the data in this study. RESULTS: The rate of ESBL-producing bacteria was 28.75-37.03% among enterobacteriaceae and the rate of MRSA was 42.75%-60% among Staphylococcus strains. The most detectable rate of the MDR bacterial isolates was Gram-negative bacteria 39 (76.47%) and Enterobacter spp. 19(70.37%) was the most multidrug resistant isolate among Gram negative bacteria. Also 36 (73.46%) of the gram positive bacterial isolated were multidrug resistance and Staphylococcus aureus 9(90%) was the most MDR among Gram positive bacteria. CONCLUSION: Antimicrobial resistance is increasing in chronic bacterial sinusitis. The emergence of MRSA and ESBL bacteria causing chronic sinusitis is increasing. PMID- 27386064 TI - Associated factors of headache in an unstudied cohort of elderly subjects. AB - BACKGROUND: Headache and depression are prevalent among general population. The aim of this study was to determine the associated factors of headache in elderly subjects with emphasis to depression. METHODS: All cohort of elderly individuals of the Amirkola Health Study Project were included. Data regarding several clinical and demographic characteristics were provided via fill in quesstionnaire, interview and clinical examination. Presence and duration as well as severity of headache were collected through an interview based on self reported data. Diagnosis of depression was confirmed according to standard Geriatric Depression Scale (GDS) criteria. In statistical analyses chi-square test with logistic regression analysis was used for association. RESULTS: A total of 832 men and 667 women aged >/= 60 years old were studied. Headache and depression were diagnosed in 42% and 42.4% respectively. In depressed subjects, headache was significantly higher by OR=3.1(95% CI, 2.5-3.83, P=0.001). Proportions of headache increased by severity of depression with a dose-response pattern of relationship from 53.3% in mild depression to 72.6% in severe depression. The magnitude of OR for headache increased from 2.59 (95% CI, 2.03 3.31) in patients with mild depression to 6.04 (95% CI, 3.54-10.3) in patients with severe depression. After adjustment for all covariates, headache was significantly associated with female gender and back pain as well as with depression with a significant dose-response relationship. CONCLUSION: The findings of this study indicated an independent association between headache and psychological factors in elderly subjects, particularly in women. PMID- 27386065 TI - Gender differences in the health status of elderly living alone compared to those who are not alone: Evidence of the AHAP study, North of Iran. AB - BACKGROUND: One of the factors that have impact on the health status of elderly people is living alone. This study was conducted to examine the living condition of elderly population in Babol and probable differences which this condition induced on the health disorders of elderly people. METHODS: This cross-sectional study was performed on 1544 elderly people aged 60 and over in Amirkola, Babol. Demographic characteristics, the incidence of falls, chronic diseases, polypharmacy, headache with uncertain cause, chronic pains and back pain were collected by the study questionnaire; social support, physical activity, depression and cognitive disorders were assessed with standard questionnaires. RESULTS: 6.8% of elderly people were living alone. Lack of social support, cognitive disorders, depression, multiple chronic diseases, occurrence of falls and headache with uncertain cause were significantly higher among those elderly who live alone (p<0.05). Regardless of age and educational level, headache and depressive symptoms in male individuals living alone, and falls occurrence in female individuals were significantly more than those who did not live alone (p<0.05). Also, in female elderly subjects, the effect of the marital status factor on health-related disorders was more than the effect of living alone factor. CONCLUSION: Many disorders and disabilities are higher in the elderly people who live alone; also there is a difference in the health status of elderly people who live alone, according to their gender. PMID- 27386066 TI - "Influence of methadone on clopidogrel in addicts on methadone maintenance therapy" Drug interaction between methadone and clopidogrel. AB - BACKGROUND: Clopidogrel is a prodrug that converts in the liver to an active thiol metabolite, which irreversibly inhibits the platelet P2Y12 adenosine diphosphate receptor. It seems that methadone as CYP2C19 inhibitor affects ticlopidine activity in vivo. This study aimed to test the ability of methadone in changing ticlopidine pharmacokinetics. METHODS: We conducted a case-control study in 10 subjects. The cases (5 subjects) in our study were addicts who were receiving methadone maintenance treatment (MMT) for preventing opium withdrawal symptoms. The control group were opiate users before starting MMT. In both groups, the patients received clopidogrel (75mg/day) for 5 days. On the 6(th) day, the subjects returned to the clinic, blood samples were taken up to 12 hours following clopidogrel dosing in case and control groups. Plasma concentration of clopidogrel was measured by GC-MAS. Noncompartmental pharmacokinetic analysis was performed using Microsoft Excel software to estimate PK parameters. RESULTS: In this study, methadone decreased clopidogrel clearance by 25% and increased the AUC0-inf nearly 1.3 fold during the coadministration of clopidogrel as an antiplatelet drug. CONCLUSION: A significant decrease in the clearance of clopidogrel during the coadministration of methadone consistent with a decrease in clopidogrel conversion to its active metabolite and this may decrease its efficacy and may have life-threatening consequences for the patients undergoing clopidogerel maintenance therapy. PMID- 27386068 TI - Deep vein thrombosis in a patient of adenomatous polyposis coli treated successfully with aspirin: A case report. AB - BACKGROUND: Deep vein thrombosis is an important cause of morbidity and mortality. However, its association with adenomatous polyposis coli is extremely rare. Here we present an interesting case of deep vein thrombosis associated with adenomatous polyposis coli. CASE PRESENTATION: A 15 year old female who was having fever and diarrhea for 5 months developed bilateral asymmetric painful swelling of lower limbs for 1 month. Doppler ultrasound of lower limbs revealed presence of thrombosis from inferior vena cava up to popliteal vein. Colonoscopy and biopsy were suggestive of adenomatous polyposis coli. However, she could not tolerate anticoagulant therapy and was put on aspirin therapy for 6 months to which she responded well with the resolution of thrombus. CONCLUSION: Role of aspirin therapy may be considered whenever a patient of venous thrombosis cannot tolerate anticoagulant therapy. PMID- 27386067 TI - Female gender and Helicobacter pylori infection, the most important predisposition factors in a cohort of gastric cancer: A longitudinal study. AB - BACKGROUND: Gastric cancer (GC) is one of the most common Cancers in the world and Helicobacter pylori (HP) infection is considered a causative factor. The aim of this study was to determine the characteristics and the associated factors of (GC) in a small cohort. METHODS: Overall, 54 patients with diagnosed gastric cancer were followed-up at the Department of Gastroenterology & Hepatology at Baqiyatallah University of Medical Sciences. 37 (68.5%) of them were positive for H pylori infection in histopathological evaluations. Univariate and multivariate regression analyses were used to determine the associations of demographic features and HP infection status with GC characteristics and prognosis. RESULTS: Univariate analysis showed female gender (odds ratio (OR): 6.53; 95% confidence interval (95%CI): 1.59-26.8; P=0.008), and illiteracy (compared to intermediate education; OR: 5.9, 95%CI: 1.37-25.43; p=0.05) were associated significantly with higher rate of HP infection. After a mean+/-SD follow-up duration of 254+/-329 months, only female gender was significantly associated with HP infection in GC (OR:4.56; 95% CI: 1.0-21.76; P=0.05). H pylori positive patients had significantly higher grade of GC (OR: 3.97; 95% CI: 1.0-16.16; P=0.05), and a trend toward greater GC stage (OR: 4.46, 95% CI: 9.39-21.23; p=0.06). There was no association between survival rate and H pylori infection. CONCLUSION: In the current study, we found a significant association of female gender with GN and an association of higher grade of GC with female gender. These findings may indicate a sex disparity in susceptibility to HP infection regarding GC future studies of larger populations are recommended. PMID- 27386069 TI - Huge epithelial nonparasitic splenic cyst: A case report and a review of treatment methods. AB - BACKGROUND: Splenic cysts are rare in all age groups and there are a few reports in the world literature. Primary cysts occur most frequently in children and young adults, comprising around 25% of all nonparasitic splenic cysts. Various techniques are suggested for the treatment of splenic cysts. In this case report, a huge epithelial splenic cyst in a 17-year-old female is presented and different treatment methods of splenic cysts are evaluated. CASE PRESENTATION: A 17-year old female presented with progressive abdominal mass in left upper quadrant associated with abdominal pain and food intolerance of duration of several months. There was no history of trauma. On physical examination, there was a huge mass located in the upper left side of abdomen. Computerized tomography scan revealed that a large cystic lesion had occupied the spleen with dimensions of 32x21xI5.6 cm. After patient preparation laparotomy was performed and complete cyst excision was done with splenectomy, patient was discharged after 2 days. This is a report of a case of epithelial splenic cyst of the spleen in a 17-year old female. CONCLUSION: The management of splenic cysts continues to evolve and the optimum treatment of patients with nonparasitic splenic cysts is controversial, as a principle preservation technique of the spleen with minimally invasive methods such as laparoscopy is preferred to splenectomy with the exception of very large cysts and when splenic hilum is involved in cyst wall. However, significant cyst recurrences were encountered with these techniques. Recently open partial splenectomy has been proposed as a safe and effective method in the management of NPSCs it ensures complete cyst removal, lack of cyst recurrence, and preservation of the spleen functions. PMID- 27386070 TI - Association of CD166 expression with clinicopathologic characteristics of colorectal cancer. PMID- 27386071 TI - The effect of diet and time after bacterial infection on fecundity, resistance, and tolerance in Drosophila melanogaster. AB - Mounting and maintaining an effective immune response in the face of infection can be costly. The outcome of infection depends on two host immune strategies: resistance and tolerance. Resistance limits pathogen load, while tolerance reduces the fitness impact of an infection. While resistance strategies are well studied, tolerance has received less attention, but is now considered to play a vital role in host-pathogen interactions in animals. A major challenge in ecoimmunology is to understand how some hosts maintain their fitness when infected while others succumb to infection, as well as how extrinsic, environmental factors, such as diet, affect defense. We tested whether dietary restriction through yeast (protein) limitation affects resistance, tolerance, and fecundity in Drosophila melanogaster. We predicted that protein restriction would reveal costs of infection. Because infectious diseases are not always lethal, we tested resistance and tolerance using two bacteria with low lethality: Escherichia coli and Lactococcus lactis. We then assayed fecundity and characterized bacterial infection pathology in individual flies at two acute phase time points after infection. As expected, our four fecundity measures all showed a negative effect of a low-protein diet, but contrary to predictions, diet did not affect resistance to either bacteria species. We found evidence for diet induced and time-dependent variation in host tolerance to E. coli, but not to L. lactis. Furthermore, the two bacteria species exhibited remarkably different infection profiles, and persisted within the flies for at least 7 days postinfection. Our results show that acute phase infections do not necessarily lead to fecundity costs despite high bacterial loads. The influence of intrinsic variables such as genotype are the prevailing factors that have been studied in relation to variation in host tolerance, but here we show that extrinsic factors should also be considered for their role in influencing tolerance strategies. PMID- 27386072 TI - Mate choice for neutral and MHC genetic characteristics in Alpine marmots: different targets in different contexts? AB - Sexual selection through female mate choice for genetic characteristics has been suggested to be an important evolutionary force maintaining genetic variation in animal populations. However, the genetic targets of female mate choice are not clearly identified and whether female mate choice is based on neutral genetic characteristics or on particular functional loci remains an open question. Here, we investigated the genetic targets of female mate choice in Alpine marmots (Marmota marmota), a socially monogamous mammal where extra-pair paternity (EPP) occurs. We used 16 microsatellites to describe neutral genetic characteristics and two MHC loci belonging to MHC class I and II as functional genetic characteristics. Our results reveal that (1) neutral and MHC genetic characteristics convey different information in this species, (2) social pairs show a higher MHC class II dissimilarity than expected under random mate choice, and (3) the occurrence of EPP increases when social pairs present a high neutral genetic similarity or dissimilarity but also when they present low MHC class II dissimilarity. Thus, female mate choice is based on both neutral and MHC genetic characteristics, and the genetic characteristics targeted seem to be context dependent (i.e., the genes involved in social mate choice and genetic mate choice differ). We emphasize the need for empirical studies of mate choice in the wild using both neutral and MHC genetic characteristics because whether neutral and functional genetic characteristics convey similar information is not universal. PMID- 27386073 TI - Scrophularia arguta, a widespread annual plant in the Canary Islands: a single recent colonization event or a more complex phylogeographic pattern? AB - Many studies have addressed evolution and phylogeography of plant taxa in oceanic islands, but have primarily focused on endemics because of the assumption that in widespread taxa the absence of morphological differentiation between island and mainland populations is due to recent colonization. In this paper, we studied the phylogeography of Scrophularia arguta, a widespread annual species, in an attempt to determine the number and spatiotemporal origins of dispersal events to Canary Islands. Four different regions, ITS and ETS from nDNA and psbA-trnH and psbJ petA from cpDNA, were used to date divergence events within S. arguta lineages and determine the phylogenetic relationships among populations. A haplotype network was obtained to elucidate the phylogenetic relationships among haplotypes. Our results support an ancient origin of S. arguta (Miocene) with expansion and genetic differentiation in the Pliocene coinciding with the aridification of northern Africa and the formation of the Mediterranean climate. Indeed, results indicate for Canary Islands three different events of colonization, including two ancient events that probably happened in the Pliocene and have originated the genetically most divergent populations into this species and, interestingly, a recent third event of colonization of Gran Canaria from mainland instead from the closest islands (Tenerife or Fuerteventura). In spite of the great genetic divergence among populations, it has not implied any morphological variation. Our work highlights the importance of nonendemic species to the genetic richness and conservation of island flora and the significance of the island populations of widespread taxa in the global biodiversity. PMID- 27386074 TI - Genetic differentiation of the pine processionary moth at the southern edge of its range: contrasting patterns between mitochondrial and nuclear markers. AB - The pine processionary moth (Thaumetopoea pityocampa) is an important pest of coniferous forests at the southern edge of its range in Maghreb. Based on mitochondrial markers, a strong genetic differentiation was previously found in this species between western (pityocampa clade) and eastern Maghreb populations (ENA clade), with the contact zone between the clades located in Algeria. We focused on the moth range in Algeria, using both mitochondrial (a 648 bp fragment of the tRNA-cox2) and nuclear (11 microsatellite loci) markers. A further analysis using a shorter mtDNA fragment and the same microsatellite loci was carried out on a transect in the contact zone between the mitochondrial clades. Mitochondrial diversity showed a strong geographical structure and a well-defined contact zone between the two clades. In particular, in the pityocampa clade, two inner subclades were found whereas ENA did not show any further structure. Microsatellite analysis outlined a different pattern of differentiation, with two main groups not overlapping with the mitochondrial clades. The inconsistency between mitochondrial and nuclear markers is probably explained by sex-biased dispersal and recent afforestation efforts that have bridged isolated populations. PMID- 27386075 TI - The effect of local land use and loss of forests on bats and nocturnal insects. AB - Land-use intensification at local and landscape level poses a serious threat to biodiversity and affects species interactions and ecosystem function. It is thus important to understand how interrelated taxa respond to land-use intensification and to consider the importance of different spatial scales. We investigated whether and how local land-use intensity and landscape features affect the predator-prey interaction of bats and insects. Bats and nocturnal insects were assessed on 50 grassland sites in the Schorfheide-Chorin. We analyzed the effect of local land use and distance to forested areas as a proxy for site accessibility on bats and insects and their biological interaction measured in bat's feeding activity. Insect abundance increased with higher land-use intensity, while size and diversity of insects decreased. In contrast, bat activity, diversity, and species composition were determined by the distance to forested areas and only slightly by land-use intensity. Feeding attempts of bats increased with higher insect abundance and diversity but decreased with insect size and distance to forested areas. Finally, our results revealed that near forested areas, the number of feeding attempts was much lower on grassland sites with high, compared to those with low land-use intensity. In contrast, far from forests, the feeding attempts did not differ significantly between intensively and extensively managed grassland sites. We conclude that the two interrelated taxa, bats and insects, respond to land-use intensification on very different scales. While insects respond to local land use, bats are rather influenced by surrounding landscape matrix. Hereby, proximity to forests reveals to be a prerequisite for higher bat species diversity and a higher rate of feeding attempts within the area. However, proximity to forest is not sufficient to compensate local high land-use intensity. Thus, local land-use intensification in combination with a loss of forest remnants weakens the interaction of bats and insects. PMID- 27386076 TI - Dispersal by rodent caching increases seed survival in multiple ways in canopy fire ecosystems. AB - Seed-caching rodents have long been seen as important actors in dispersal ecology. Here, we focus on the interactions with plants in a fire-disturbance community, specifically Arctostaphylos species (Ericaceae) in California chaparral. Although mutualistic relationships between caching rodents and plants are well studied, little is known how this type of relationship functions in a disturbance-driven system, and more specifically to systems shaped by fire disturbance. By burying seeds in the soil, rodents inadvertently improve the probability of seed surviving high temperatures produced by fire. We test two aspects of vertical dispersal, depth of seed and multiple seeds in caches as two important dimensions of rodent-caching behavior. We used a laboratory experimental approach to test seed survival under different heating conditions and seed bank structures. Creating a synthetic soil seed bank and synthetic fire/heating in the laboratory allowed us to have control over surface heating, depth of seed in the soil, and seed cache size. We compared the viability of Arctostaphylos viscida seeds from different treatment groups determined by these factors and found that, as expected, seeds slightly deeper in the soil had substantial increased chances of survival during a heating event. A key result was that some seeds within a cache in shallow soil could survive fire even at a depth with a killing heat pulse compared to isolated seeds; temperature measurements indicated lower temperatures immediately below caches compared to the same depth in adjacent soil. These results suggest seed caching by rodents increases seed survival during fire events in two ways, that caches disrupt heat flow or that caches are buried below the heat pulse kill zone. The context of natural disturbance drives the significance of this mutualism and further expands theory regarding mutualisms into the domain of disturbance-driven systems. PMID- 27386077 TI - Nuclear locus divergence at the early stages of speciation in the Orchard Oriole complex. AB - As two lineages diverge from one another, mitochondrial DNA should evolve fixed differences more rapidly than nuclear DNA due to its smaller effective population size and faster mutation rate. As a consequence, molecular systematists have focused on the criteria of reciprocal monophyly in mitochondrial DNA for delimiting species boundaries. However, mitochondrial gene trees do not necessarily reflect the evolutionary history of the taxa in question, and even mitochondrial loci are not expected to be reciprocally monophyletic when the speciation event happened very recently. The goal of this study was to examine mitochondrial paraphyly within the Orchard Oriole complex, which is composed of Icterus spurius (Orchard Oriole) and Icterus fuertesi (Fuertes' Oriole). We increased the geographic sampling, added four nuclear loci, and used a range of population genetic and coalescent methods to examine the divergence between the taxa. With increased taxon sampling, we found evidence of clear structure between the taxa for mitochondrial DNA. However, nuclear loci showed little evidence of population structure, indicating a very recent divergence between I. spurius and I. fuertesi. Another goal was to examine the genetic variation within each taxon to look for evidence of a past founder event within the I. fuertesi lineage. Based on the high amounts of genetic variation for all nuclear loci, we found no evidence of such an event - thus, we found no support for the possible founding of I. fuertesi through a change in migratory behavior, followed by peripheral isolates speciation. Our results demonstrate that these two taxa are in the earliest stages of speciation, at a point when they have fixed differences in plumage color that are not reflected in monophyly of the mitochondrial or nuclear DNA markers in this study. This very recent divergence makes them ideal for continued studies of species boundaries and the earliest stages of speciation. PMID- 27386078 TI - Consequences of elevated temperature and pCO2 on insect folivory at the ecosystem level: perspectives from the fossil record. AB - Paleoecological studies document the net effects of atmospheric and climate change in a natural laboratory over timescales not accessible to laboratory or ecological studies. Insect feeding damage is visible on well-preserved fossil leaves, and changes in leaf damage through time can be compared to environmental changes. We measured percent leaf area damaged on four fossil leaf assemblages from the Bighorn Basin, Wyoming, that range in age from 56.1 to 52.65 million years (Ma). We also include similar published data from three US sites 49.4 to ~45 Ma in our analyses. Regional climate was subtropical or warmer throughout this period, and the second oldest assemblage (56 Ma) was deposited during the Paleocene-Eocene Thermal Maximum (PETM), a geologically abrupt global warming event caused by massive release of carbon into the atmosphere. Total and leaf chewing damage are highest during the PETM, whether considering percent area damaged on the bulk flora, the average of individual host plants, or a single plant host that occurs at multiple sites. Another fossil assemblage in our study, the 52.65 Ma Fifteenmile Creek paleoflora, also lived during a period of globally high temperature and pCO 2, but does not have elevated herbivory. Comparison of these two sites, as well as regression analyses conducted on the entire dataset, demonstrates that, over long timescales, temperature and pCO 2 are uncorrelated with total insect consumption at the ecosystem level. Rather, the most important factor affecting herbivory is the relative abundance of plants with nitrogen fixing symbionts. Legumes dominate the PETM site; their prevalence would have decreased nitrogen limitation across the ecosystem, buffering generalist herbivore populations against decreased leaf nutritional quality that commonly occurs at high pCO 2. We hypothesize that nitrogen concentration regulates the opposing effects of elevated temperature and CO 2 on insect abundance and thereby total insect consumption, which has important implications for agricultural practices in today's world of steadily increasing pCO 2. PMID- 27386079 TI - Plant-fungus competition for nitrogen erases mycorrhizal growth benefits of Andropogon gerardii under limited nitrogen supply. AB - Considered to play an important role in plant mineral nutrition, arbuscular mycorrhizal (AM) symbiosis is a common relationship between the roots of a great majority of plant species and glomeromycotan fungi. Its effects on the plant host are highly context dependent, with the greatest benefits often observed in phosphorus (P)-limited environments. Mycorrhizal contribution to plant nitrogen (N) nutrition is probably less important under most conditions. Moreover, inasmuch as both plant and fungi require substantial quantities of N for their growth, competition for N could potentially reduce net mycorrhizal benefits to the plant under conditions of limited N supply. Further compounded by increased belowground carbon (C) drain, the mycorrhizal costs could outweigh the benefits under severe N limitation. Using a field AM fungal community or a laboratory culture of Rhizophagus irregularis as mycorrhizal inoculants, we tested the contribution of mycorrhizal symbiosis to the growth, C allocation, and mineral nutrition of Andropogon gerardii growing in a nutrient-poor substrate under variable N and P supplies. The plants unambiguously competed with the fungi for N when its supply was low, resulting in no or negative mycorrhizal growth and N uptake responses under such conditions. The field AM fungal communities manifested their potential to improve plant P nutrition only upon N fertilization, whereas the R. irregularis slightly yet significantly increased P uptake of its plant host (but not the host's growth) even without N supply. Coincident with increasing levels of root colonization by the AM fungal structures, both inoculants invariably increased nutritional and growth benefits to the host with increasing N supply. This, in turn, resulted in relieving plant P deficiency, which was persistent in non-mycorrhizal plants across the entire range of nutrient supplies. PMID- 27386080 TI - Merging and comparing three mitochondrial markers for phylogenetic studies of Eurasian reindeer (Rangifer tarandus). AB - Phylogenetic analyses provide information that can be useful in the conservation of genetic variation by identifying intraspecific genetic structure. Reconstruction of phylogenetic relationships requires the use of markers with the appropriate amount of variation relative to the timeframe and purpose of the study. Here, genetic structure and clustering are inferred from comparative analyses of three widely used mitochondrial markers, the CR, cytb and the COI region, merged and separately, using Eurasian reindeer as a model. A Bayesian phylogeny and a MJ network, both based on the merged dataset, indicate several distinct maternal haplotype clusters within Eurasian reindeer. In addition to confirm previously described clusters, two new subclusters were found. When comparing the results from the merged dataset with the results from analyses of the three markers separately, similar clustering was found in the CR and COI phylogenies, whereas the cytb region showed poor resolution. Phylogenetic analyses of the merged dataset and the CR revealed congruent results, implying that single sequencing analysis of the CR is an applicable method for studying the haplotype structure in Eurasian reindeer. PMID- 27386081 TI - Scaling up functional traits for ecosystem services with remote sensing: concepts and methods. AB - Ecosystem service-based management requires an accurate understanding of how human modification influences ecosystem processes and these relationships are most accurate when based on functional traits. Although trait variation is typically sampled at local scales, remote sensing methods can facilitate scaling up trait variation to regional scales needed for ecosystem service management. We review concepts and methods for scaling up plant and animal functional traits from local to regional spatial scales with the goal of assessing impacts of human modification on ecosystem processes and services. We focus our objectives on considerations and approaches for (1) conducting local plot-level sampling of trait variation and (2) scaling up trait variation to regional spatial scales using remotely sensed data. We show that sampling methods for scaling up traits need to account for the modification of trait variation due to land cover change and species introductions. Sampling intraspecific variation, stratification by land cover type or landscape context, or inference of traits from published sources may be necessary depending on the traits of interest. Passive and active remote sensing are useful for mapping plant phenological, chemical, and structural traits. Combining these methods can significantly improve their capacity for mapping plant trait variation. These methods can also be used to map landscape and vegetation structure in order to infer animal trait variation. Due to high context dependency, relationships between trait variation and remotely sensed data are not directly transferable across regions. We end our review with a brief synthesis of issues to consider and outlook for the development of these approaches. Research that relates typical functional trait metrics, such as the community-weighted mean, with remote sensing data and that relates variation in traits that cannot be remotely sensed to other proxies is needed. Our review narrows the gap between functional trait and remote sensing methods for ecosystem service management. PMID- 27386082 TI - Are the metabolomic responses to folivory of closely related plant species linked to macroevolutionary and plant-folivore coevolutionary processes? AB - The debate whether the coevolution of plants and insects or macroevolutionary processes (phylogeny) is the main driver determining the arsenal of molecular defensive compounds of plants remains unresolved. Attacks by herbivorous insects affect not only the composition of defensive compounds in plants but also the entire metabolome. Metabolomes are the final products of genotypes and are constrained by macroevolutionary processes, so closely related species should have similar metabolomic compositions and may respond in similar ways to attacks by folivores. We analyzed the elemental compositions and metabolomes of needles from three closely related Pinus species with distant coevolutionary histories with the caterpillar of the processionary moth respond similarly to its attack. All pines had different metabolomes and metabolic responses to herbivorous attack. The metabolomic variation among the species and the responses to folivory reflected their macroevolutionary relationships, with P. pinaster having the most divergent metabolome. The concentrations of terpenes were in the attacked trees supporting the hypothesis that herbivores avoid plant individuals with higher concentrations. Our results suggest that macroevolutionary history plays important roles in the metabolomic responses of these pine species to folivory, but plant-insect coevolution probably constrains those responses. Combinations of different evolutionary factors and trade-offs are likely responsible for the different responses of each species to folivory, which is not necessarily exclusively linked to plant-insect coevolution. PMID- 27386083 TI - The effect of terrain and female density on survival of neonatal white-tailed deer and mule deer fawns. AB - Juvenile survival is a highly variable life-history trait that is critical to population growth. Antipredator tactics, including an animal's use of its physical and social environment, are critical to juvenile survival. Here, we tested the hypothesis that habitat and social characteristics influence coyote (Canis latrans) predation on white-tailed deer (Odocoileus virginianus) and mule deer (O. hemionus) fawns in similar ways during the neonatal period. This would contrast to winter when the habitat and social characteristics that provide the most safety for each species differ. We monitored seven cohorts of white-tailed deer and mule deer fawns at a grassland study site in Alberta, Canada. We used logistic regression and a model selection procedure to determine how habitat characteristics, climatic conditions, and female density influenced fawn survival during the first 8 weeks of life. Fawn survival improved after springs with productive vegetation (high integrated Normalized Difference Vegetation Index values). Fawns that used steeper terrain were more likely to survive. Fawns of both species had improved survival in years with higher densities of mule deer females, but not with higher densities of white-tailed deer females, as predicted if they benefit from protection by mule deer. Our results suggest that topographical variation is a critical resource for neonates of many ungulate species, even species like white-tailed deer that use more gentle terrain when older. Further, our results raise the possibility that neonatal white-tailed fawns may benefit from associating with mule deer females, which may contribute to the expansion of white-tailed deer into areas occupied by mule deer. PMID- 27386084 TI - The oceanic concordance of phylogeography and biogeography: a case study in Notochthamalus. AB - Dispersal and adaptation are the two primary mechanisms that set the range distributions for a population or species. As such, understanding how these mechanisms interact in marine organisms in particular - with capacity for long range dispersal and a poor understanding of what selective environments species are responding to - can provide useful insights for the exploration of biogeographic patterns. Previously, the barnacle Notochthamalus scabrosus has revealed two evolutionarily distinct lineages with a joint distribution that suggests an association with one of the two major biogeographic boundaries (~30 degrees S) along the coast of Chile. However, spatial and genomic sampling of this system has been limited until now. We hypothesized that given the strong oceanographic and environmental shifts associated with the other major biogeographic boundary (~42 degrees S) for Chilean coastal invertebrates, the southern mitochondrial lineage would dominate or go to fixation in locations further to the south. We also evaluated nuclear polymorphism data from 130 single nucleotide polymorphisms to evaluate the concordance of the signal from the nuclear genome with that of the mitochondrial sample. Through the application of standard population genetic approaches along with a Lagrangian ocean connectivity model, we describe the codistribution of these lineages through a simultaneous evaluation of coastal lineage frequencies, an approximation of larval behavior, and current-driven dispersal. Our results show that this pattern could not persist without the two lineages having distinct environmental optima. We suggest that a more thorough integration of larval dynamics, explicit dispersal models, and near-shore environmental analysis can explain much of the coastal biogeography of Chile. PMID- 27386085 TI - Major histocompatibility complex class II DAB alleles associated with intestinal parasite load in the vulnerable Chinese egret (Egretta eulophotes). AB - The maintenance of major histocompatibility complex (MHC) polymorphism has been hypothesized to result from many mechanisms such as rare-allele advantage, heterozygote advantage, and allele counting. In the study reported herein, 224 vulnerable Chinese egrets (Egretta eulophotes) were used to examine these hypotheses as empirical results derived from bird studies are rare. Parasite survey showed that 147 (65.63%) individuals were infected with 1-3 helminths, and 82.31% of these infected individuals carried Ascaridia sp. Using asymmetric polymerase chain reaction technique, 10 DAB1, twelve DAB2, and three DAB3 exon 2 alleles were identified at each single locus. A significant association of the rare allele Egeu-DAB2*05 (allele frequency: 0.022) with helminth resistance was found for all helminths, as well as for the most abundant morphotype Ascaridia sp. in the separate analyses. Egeu-DAB2*05 occurred frequently in uninfected individuals, and individuals carrying Egeu-DAB2*05 had significantly lower helminth morphotypes per individual (HMI) (the number of HMI) and the fecal egg count values. Further, the parasite infection measurements were consistently lower in individuals with an intermediate number of different alleles in the duplicated DAB loci. Significantly, heterozygosity within each DAB locus was not correlated with any parasite infection measurements. These results indicate that the diversity in MHC Egeu-DAB gene is associated with intestinal parasite load and maintained by pathogen-driven selection that probably operate through both the rare-allele advantage and the allele counting strategy, and suggest that Egeu DAB2*05 might be a valuable indicator of better resistance to helminth diseases in the vulnerable Chinese egret. PMID- 27386086 TI - Late Pleistocene climate change promoted divergence between Picea asperata and P. crassifolia on the Qinghai-Tibet Plateau through recent bottlenecks. AB - Divergence during the early stage of speciation can be driven by a population bottleneck via reduced gene flow and enhanced lineage sorting. In this study, we aimed to examine whether such bottlenecks occurred during the initial speciation of two closely related spruce species Picea asperata and P. crassifolia occurring on the Qinghai-Tibet Plateau (QTP). We analyzed sequences of three chloroplast, two mitochondrial DNA fragments and a further 13 nuclear loci from 216 individuals of the two species. Both species showed a low level of genetic diversity in contrast to other congeners occurring in the QTP and adjacent regions. The estimated population sizes of P. asperata and P. crassifolia are less than the ancestral population size before splitting. These results together with multiple statistical tests (Tajima's D, Fu and Li's D* and F*) suggest that these two species underwent recent bottlenecks. Based on approximate Bayesian computation (ABC), we also determined that the period of the population shrinkage was consistent with the interspecific divergence during the late Pleistocene. The reduced population sizes and the divergent selection may together have triggered the initial divergence under high gene flow between these two species. Our results therefore highlight the importance of climatic oscillations during the late Pleistocene in promoting speciation through changing demographic sizes of the ancestral species on the QTP and in adjacent regions. PMID- 27386087 TI - Frogs in the spotlight: a 16-year survey of native frogs and invasive toads on a floodplain in tropical Australia. AB - Although widespread declines in anuran populations have attracted considerable concern, the stochastic demographics of these animals make it difficult to detect consistent trends against a background of spatial and temporal variation. To identify long-term trends, we need datasets gathered over long time periods, especially from tropical areas where anuran biodiversity is highest. We conducted road surveys of four anurans in the Australian wet-dry tropics on 4637 nights over a 16-year period. Our surveys spanned the arrival of invasive cane toads (Rhinella marina), allowing us to assess the invader's impact on native anuran populations. Our counts demonstrate abrupt and asynchronous shifts in abundance and species composition from one year to the next, not clearly linked to rainfall patterns. Typically, periods of decline in numbers of a species were limited to 1 2 years and were followed by 1- to 2-year periods of increase. No taxa showed consistent declines over time, although trajectories for some species showed significant perturbations coincident with the arrival of toads. None of the four focal frog species was less common at the end of the study than at the beginning, and three of the species reached peak abundances after toad arrival. Survey counts of cane toads increased rapidly during the initial stage of invasion but have subsequently declined and fluctuated. Distinguishing consistent declines versus stochastic fluctuations in anuran populations requires extensive time series analysis, coupled with an understanding of the shifts expected under local climatic conditions. This is especially pertinent when assessing impacts of specific perturbations such as invasive species. PMID- 27386088 TI - A recipe for postfledging survival in great tits Parus major: be large and be early (but not too much). AB - Survival of juveniles during the postfledging period can be markedly low, which may have major consequences on avian population dynamics. Knowing which factors operating during the nesting phase affect postfledging survival is crucial to understand avian breeding strategies. We aimed to obtain a robust set of predictors of postfledging local survival using the great tit (Parus major) as a model species. We used mark-recapture models to analyze the effect of hatching date, temperatures experienced during the nestling period, fledging size and body mass on first-year postfledging survival probability of great tit juveniles. We used data from 5192 nestlings of first clutches ringed between 1993 and 2010. Mean first-year postfledging survival probability was 15.2%, and it was lower for smaller individuals, as well as for those born in either very early or late broods. Our results stress the importance of choosing an optimum hatching period, and raising large chicks to increase first-year local survival probability in the studied population. PMID- 27386089 TI - Weighing the relative potential impacts of climate change and land-use change on an endangered bird. AB - Climate change and land-use change are projected to be the two greatest drivers of biodiversity loss over the coming century. Land-use change has resulted in extensive habitat loss for many species. Likewise, climate change has affected many species resulting in range shifts, changes in phenology, and altered interactions. We used a spatially explicit, individual-based model to explore the effects of land-use change and climate change on a population of the endangered Red-cockaded Woodpecker (RCW; Picoides borealis). We modeled the effects of land use change using multiple scenarios representing different spatial arrangements of new training areas for troops across Fort Benning. We used projected climate driven changes in habitat and changes in reproductive output to explore the potential effects of climate change. We summarized potential changes in habitat based on the output of the dynamic vegetation model LPJ-GUESS, run for multiple climate change scenarios through the year 2100. We projected potential changes in reproduction based on an empirical relationship between spring precipitation and the mean number of successful fledglings produced per nest attempt. As modeled in our study, climate change had virtually no effect on the RCW population. Conversely, simulated effects of land-use change resulted in the loss of up to 28 breeding pairs by 2100. However, the simulated impacts of development depended on where the development occurred and could be completely avoided if the new training areas were placed in poor-quality habitat. Our results demonstrate the flexibility inherent in many systems that allows seemingly incompatible human land uses, such as development, and conservation actions to exist side by side. PMID- 27386090 TI - Do differences in life-history traits and the timing of peak mating activity between host-associated populations of Chilo suppressalis have a genetic basis? AB - The development of host races, genetically distinct populations of the same species with different hosts, is considered to be the initial stage of ecological speciation. Ecological and biological differences consistent with host race formation have been reported between water-oat and rice-associated populations of Chilo suppressalis. In order to confirm whether these differences have a genetic basis, we conducted experiments to determine the extent to which various life history traits and the time of peak mating activity of these populations were influenced by the species of host plant larvae were raised on. Individuals from each population were reared for three consecutive generations on either water-oat fruit pulp or rice seedlings. Descendants of both populations had higher larval survival rates, shorter larval developmental periods, higher pupal weight, and longer adult forewings, when reared on water-oats than when reared on rice. The time of peak of mating activity differed between the descendants of each population, irrespective of whether they were raised on water-oats or rice. These results indicate that although some life-history traits of host-associated populations of C. suppressalis are influenced by the host plant larvae are raised on, time of peak mating activity is not. Because it is a stable, objective, phenotypic trait, further research on difference in the time of peak mating activity between host-associated populations of C. suppressalis should be conducted to clarify the mechanism responsible for host race formation in this species. PMID- 27386092 TI - Digital fragment analysis of short tandem repeats by high-throughput amplicon sequencing. AB - High-throughput sequencing has been proposed as a method to genotype microsatellites and overcome the four main technical drawbacks of capillary electrophoresis: amplification artifacts, imprecise sizing, length homoplasy, and limited multiplex capability. The objective of this project was to test a high throughput amplicon sequencing approach to fragment analysis of short tandem repeats and characterize its advantages and disadvantages against traditional capillary electrophoresis. We amplified and sequenced 12 muskrat microsatellite loci from 180 muskrat specimens and analyzed the sequencing data for precision of allele calling, propensity for amplification or sequencing artifacts, and for evidence of length homoplasy. Of the 294 total alleles, we detected by sequencing, only 164 alleles would have been detected by capillary electrophoresis as the remaining 130 alleles (44%) would have been hidden by length homoplasy. The ability to detect a greater number of unique alleles resulted in the ability to resolve greater population genetic structure. The primary advantages of fragment analysis by sequencing are the ability to precisely size fragments, resolve length homoplasy, multiplex many individuals and many loci into a single high-throughput run, and compare data across projects and across laboratories (present and future) with minimal technical calibration. A significant disadvantage of fragment analysis by sequencing is that the method is only practical and cost-effective when performed on batches of several hundred samples with multiple loci. Future work is needed to optimize throughput while minimizing costs and to update existing microsatellite allele calling and analysis programs to accommodate sequence-aware microsatellite data. PMID- 27386091 TI - Is individual consistency in body mass and reproductive decisions linked to individual specialization in foraging behavior in a long-lived seabird? AB - Individual specialization in diet or foraging behavior within apparently generalist populations has been described for many species, especially in polar and temperate marine environments, where resource distribution is relatively predictable. It is unclear, however, whether and how increased environmental variability - and thus reduced predictability of resources - due to global climate change will affect individual specialization. We determined the within- and among-individual components of the trophic niche and the within-individual repeatability of delta(13)C and delta(15)N in feathers and red blood cells of individual female southern rockhopper penguins (Eudyptes chrysocome) across 7 years. We also investigated the effect of environmental variables (Southern Annular Mode, Southern Oscillation Index, and local sea surface temperature anomaly) on the isotopic values, as well as the link between stable isotopes and female body mass, clutch initiation dates, and total clutch mass. We observed consistent red blood cell delta(13)C and delta(15)N values within individuals among years, suggesting a moderate degree of within-individual specialization in C and N during the prebreeding period. However, the total niche width was reduced and individual specialization not present during the premolt period. Despite significant interannual differences in isotope values of C and N and environmental conditions, none of the environmental variables were linked to stable isotope values and thus able to explain phenotypic plasticity. Furthermore, neither the within-individual nor among-individual effects of stable isotopes were found to be related to female body mass, clutch initiation date, or total clutch mass. In conclusion, our results emphasize that the degree of specialization within generalist populations can vary over the course of 1 year, even when being consistent within the same season across years. We were unable to confirm that environmental variability counteracts individual specialization in foraging behavior, as phenotypic plasticity in delta(13)C and delta(15)N was not linked to any of the environmental variables studied. PMID- 27386094 TI - Distribution and diversity of diatom assemblages in surficial sediments of shallow lakes in Wapusk National Park (Manitoba, Canada) region of the Hudson Bay Lowlands. AB - The hydrology of shallow lakes (and ponds) located in the western Hudson Bay Lowlands (HBL) is sensitive to climate warming and associated permafrost thaw. However, their biological characteristics are poorly known, which hampers effective aquatic ecosystem monitoring. Located in northern Manitoba along the southwestern coast of Hudson Bay, Wapusk National Park (WNP) encompasses numerous shallow lakes representative of the subarctic zone. We analyzed the distribution and diversity of diatom (microscopic algae; class Bacillariophyceae) assemblages in surficial sediments of 33 lakes located in three different ecozones spanning a vegetation gradient, from NE to SW: the Coastal Fen (CF), the Interior Peat Plateau (IPP), and the Boreal Spruce Forest (BSF). We found significant differences (P < 0.05) in diatom community composition between CF and IPP lakes, and CF and BSF lakes, but not between IPP and BSF lakes. These results are consistent with water chemistry measurements, which indicated distinct limnological conditions for CF lakes. Diatom communities in CF lakes were generally dominated by alkaliphilous taxa typical of waters with medium to high conductivity, such as Nitzschia denticula. In contrast, several IPP and BSF lakes were dominated by acidophilous and circumneutral diatom taxa with preference for low conductivity (e.g., Tabellaria flocculosa, Eunotia mucophila, E. necompacta var. vixcompacta). This exploratory survey provides a first detailed inventory of the diatom assemblages in the WNP region needed for monitoring programs to detect changes in shallow lake ecosystems and ecozonal shifts in response to climate variations. PMID- 27386093 TI - Genomic heterogeneity of historical gene flow between two species of newts inferred from transcriptome data. AB - The role of gene flow in species formation is a major unresolved issue in speciation biology. Progress in this area requires information on the long-term patterns of gene flow between diverging species. Here, we used thousands of single-nucleotide polymorphisms derived from transcriptome resequencing and a method modeling the joint frequency spectrum of these polymorphisms to reconstruct patterns of historical gene flow between two Lissotriton newts: L. vulgaris (Lv) and L. montandoni (Lm). We tested several models of divergence including complete isolation and various scenarios of historical gene flow. The model of secondary contact received the highest support. According to this model, the species split from their common ancestor ca. 5.5 million years (MY) ago, evolved in isolation for ca. 2 MY, and have been exchanging genes for the last 3.5 MY Demographic changes have been inferred in both species, with the current effective population size of ca. 0.7 million in Lv and 0.2 million in Lm. The postdivergence gene flow resulted in two-directional introgression which affected the genomes of both species, but was more pronounced from Lv to Lm. Interestingly, we found evidence for genomic heterogeneity of interspecific gene flow. This study demonstrates the complexity of long-term gene flow between distinct but incompletely reproductively isolated taxa which divergence was initiated millions of years ago. PMID- 27386095 TI - Mating system, population growth, and management scenario for Kalanchoe pinnata in an invaded seasonally dry tropical forest. AB - Ecological invasions are a major issue worldwide, where successful invasion depends on traits that facilitate dispersion, establishment, and population growth. The nonnative succulent plant Kalanchoe pinnata, reported as invasive in some countries, is widespread in remnants of seasonally dry tropical forest on a volcanic outcrop with high conservation value in east-central Mexico where we assessed its mating system and demographic growth and identified management strategies. To understand its local mating system, we conducted hand-pollination treatments, germination, and survival experiments. Based on the experimental data, we constructed a life-stage population matrix, identified the key traits for population growth, weighted the contributions of vegetative and sexual reproduction, and evaluated management scenarios. Hand-pollination treatments had slight effects on fruit and seed setting, as well as on germination. With natural pollination treatment, the successful germination of seeds from only 2/39 fruit suggests occasional effective natural cross-pollination. The ratios of the metrics for self- and cross-pollinated flowers suggest that K. pinnata is partially self-compatible. Most of the pollinated flowers developed into fruit, but the seed germination and seedling survival rates were low. Thus, vegetative propagation and juvenile survival are the main drivers of population growth. Simulations of a virtual K. pinnata population suggest that an intense and sustained weeding campaign will reduce the population within at least 10 years. Synthesis and applications. The study population is partially self-compatible, but sexual reproduction by K. pinnata is limited at the study site, and population growth is supported by vegetative propagation and juvenile survival. Demographic modeling provides key insights and realistic forecasts on invasion process and therefore is useful to design management strategies. PMID- 27386096 TI - Application of Concanavalin A during immune responsiveness skin-swelling tests facilitates measurement interpretation in mammalian ecology. AB - The skin-swelling test is a simple and widespread method used in field ecological research to estimate cellular immune responsiveness in animals. This immunoecological test is based on measuring the magnitude of tissue swelling response at specific times following subcutaneous application of an experimental pro-inflammatory stimulant. In the vast majority of studies across vertebrate taxa, phytohemagglutinin (PHA) is used as a universal stimulant. Given the complexity of immune response activation pathways of PHA, however, interpretation of test results can be ambiguous. Goal of this study was to improve methodology of the skin-swelling test to decrease this ambiguity. Here, we present an alternative protocol aimed at facilitating interpretation of skin-swelling data for mammals. Based on previous evidence suggesting that mammalian T cells are readily activated by Concanavalin A (ConA) in vitro, we compared cellular immune responses in vivo to PHA and ConA as an alternative pro-inflammatory stimulant in mice. We measured magnitude of tissue swelling and compared it with intensity of blood cell infiltration into tissue over a 72-hour interval. Our results corroborate that PHA and ConA show important differences in both dynamics and response amplitude in rodents. ConA induces stronger swelling with a distinct leukocyte activity pattern and higher pro-inflammatory cytokine (interleukin 6 [IL-6] and interferon gamma[IFN-gamma]) expression than PHA during peak response (24-h post-treatment). Furthermore, unlike PHA, magnitude of swelling was positively associated with cellular activity (number of neutrophils infiltrating tissue) following ConA injection. We conclude that ConA is the more suitable stimulant for skin-swelling tests in mammals. This is because of the molecular binding specificity in the two lectins, that is, ConA specifically activates T cells while PHA also triggers erythroagglutination. We propose that ConA be used in all future ecological testing in mammals as it exhibits better performance and its application facilitates immunological interpretation of skin-swelling test results. PMID- 27386097 TI - Bud phenology and growth are subject to divergent selection across a latitudinal gradient in Populus angustifolia and impact adaptation across the distributional range and associated arthropods. AB - Temperate forest tree species that span large geographical areas and climatic gradients often have high levels of genetic variation. Such species are ideal for testing how neutral demographic factors and climate-driven selection structure genetic variation within species, and how this genetic variation can affect ecological communities. Here, we quantified genetic variation in vegetative phenology and growth traits in narrowleaf cottonwood, Populus angustifolia, using three common gardens planted with genotypes originating from source populations spanning the species' range along the Rocky Mountains of North America (ca. 1700 km). We present three main findings. First, we found strong evidence of divergent selection (Q ST > F ST) on fall phenology (bud set) with adaptive consequences for frost avoidance. We also found evidence for selection on bud flush duration, tree height, and basal diameter, resulting in population differentiation. Second, we found strong associations with climate variables that were strongly correlated with latitude of origin. More strongly differentiated traits also showed stronger climate correlations, which emphasizes the role that climate has played in divergent selection throughout the range. We found population * garden interaction effects; for some traits, this accounted for more of the variance than either factor alone. Tree height was influenced by the difference in climate of the source and garden locations and declined with increasing transfer distance. Third, growth traits were correlated with dependent arthropod community diversity metrics. Synthesis. Overall, we conclude that climate has influenced genetic variation and structure in phenology and growth traits and leads to local adaptation in P. angustifolia, which can then impact dependent arthropod species. Importantly, relocation of genotypes far northward or southward often resulted in poor growth, likely due to a phenological mismatch with photoperiod, the proximate cue for fall growth cessation. Genotypes moved too far southward suffer from early growth cessation, whereas those moved too far northward are prone to fall frost and winter dieback. In the face of current and forecasted climate change, habitat restoration, forestry, and tree breeding efforts should utilize these findings to better match latitudinal and climatic source environments with management locations for optimal future outcomes. PMID- 27386098 TI - Behavioral buffering of global warming in a cold-adapted lizard. AB - Alpine lizards living in restricted areas might be particularly sensitive to climate change. We studied thermal biology of Iberolacerta cyreni in high mountains of central Spain. Our results suggest that I. cyreni is a cold-adapted thermal specialist and an effective thermoregulator. Among ectotherms, thermal specialists are more threatened by global warming than generalists. Alpine lizards have no chance to disperse to new suitable habitats. In addition, physiological plasticity is unlikely to keep pace with the expected rates of environmental warming. Thus, lizards might rely on their behavior in order to deal with ongoing climate warming. Plasticity of thermoregulatory behavior has been proposed to buffer the rise of environmental temperatures. Therefore, we studied the change in body and environmental temperatures, as well as their relationships, for I. cyreni between the 1980s and 2012. Air temperatures have increased more than 3.5 degrees C and substrate temperatures have increased by 6 degrees C in the habitat of I. cyreni over the last 25 years. However, body temperatures of lizards have increased less than 2 degrees C in the same period, and the linear relationship between body and environmental temperatures remains similar. These results show that alpine lizards are buffering the potential impact of the increase in their environmental temperatures, most probably by means of their behavior. Body temperatures of I. cyreni are still cold enough to avoid any drop in fitness. Nonetheless, if warming continues, behavioral buffering might eventually become useless, as it would imply spending too much time in shelter, losing feeding, and mating opportunities. Eventually, if body temperature exceeds the thermal optimum in the near future, fitness would decrease abruptly. PMID- 27386099 TI - Ungulate browsers promote herbaceous layer diversity in logged temperate forests. AB - Ungulates are leading drivers of plant communities worldwide, with impacts linked to animal density, disturbance and vegetation structure, and site productivity. Many ecosystems have more than one ungulate species; however, few studies have specifically examined the combined effects of two or more species on plant communities. We examined the extent to which two ungulate browsers (moose [Alces americanus]) and white-tailed deer [Odocoileus virginianus]) have additive (compounding) or compensatory (opposing) effects on herbaceous layer composition and diversity, 5-6 years after timber harvest in Massachusetts, USA. We established three combinations of ungulates using two types of fenced exclosures none (full exclosure), deer (partial exclosure), and deer + moose (control) in six replicated blocks. Species composition diverged among browser treatments, and changes were generally additive. Plant assemblages characteristic of closed canopy forests were less abundant and assemblages characteristic of open/disturbed habitats were more abundant in deer + moose plots compared with ungulate excluded areas. Browsing by deer + moose resulted in greater herbaceous species richness at the plot scale (169 m(2)) and greater woody species richness at the subplot scale (1 m(2)) than ungulate exclusion and deer alone. Browsing by deer + moose resulted in strong changes to the composition, structure, and diversity of forest herbaceous layers, relative to areas free of ungulates and areas browed by white-tailed deer alone. Our results provide evidence that moderate browsing in forest openings can promote both herbaceous and woody plant diversity. These results are consistent with the classic grazing-species richness curve, but have rarely been documented in forests. PMID- 27386100 TI - Effect of tamarind (Tamarindus indica L.) seed on antioxidant activity, phytocompounds, physicochemical characteristics, and sensory acceptability of enriched cookies and mango juice. AB - Tamarind seeds are not consumed despite their high antioxidative activity. In this study, 0-10% tamarind seed powder (TSP) was incorporated into mango juice and cookies. Total phenolics (Folin-Ciocalteu assay), antioxidant activity (2,2 diphenyl-1 picrylhydrazyl (DPPH) radical scavenging assay), flavonoid (aluminum chloride assay), condensed tannins content (Vanillin-HCl assay), and consumer acceptability (n = 50) of the products were determined. TSP increased the pH and viscosity and reduced titratable acidity of juice. Incorporation of TSP increased the: total phenolic content (6.84 +/- 0.21 to 88.44 +/- 0.8 mg GAE/100 mL); flavonoid (4.64 +/- 0.03-21.7 +/- 0.36 mg CE/100 mL); condensed tannins (0.24 +/- 0.01-21.81 +/- 0.08 mg CE/100 mL) and total antioxidant activity (4.65 +/- 0.88 21.70 +/- 0.03 mg VCE/100 mL) of juice. A similar trend was observed for cookies. Maximum sensorially acceptable TSP levels were 1.5% and 6%, respectively, for juice and cookies. TSP can thus be utilized as a source of natural antioxidants in food products. PMID- 27386101 TI - Effect of environment and genotypes on the physicochemical quality of the grains of newly developed wheat inbred lines. AB - To meet the increased demand for wheat consumption, wheat cultivation in Sudan expanded southward to latitudes lower than 15 degrees N, entering a new and warmer environment. Consequently, wheat breeders developed several wheat genotypes with high yields under these environmental conditions; however, the evaluation of the end-use quality of these genotypes is scarce. In this study, we assessed the end-use quality attributes of 20 wheat genotypes grown in three different environments in the Sudan (Wad Medani, Hudeiba, and Dongola). The results showed significant differences (P <= 0.01) in all quality tests among environments, genotypes and genotypes Versus environments. The findings obtained, covered wide ranges of test weight (TW, 76.6-85.25 kg/hL), thousand kernel weight (TKW, 28.70-48.48 g), protein (PC, 9.96-14.06%), wet gluten (WG, 28.63-46.53%), gluten index (GI, 36.36-92.77%), water holding capacity (WHC, 168.42-219.32%), falling number (FN, 508.00-974.67 sec), and sedimentation value (SV, 19.00-40.00 mL). Analysis of the traits, genotypes, and traits versus genotypes showed varied correlations in the three growing environments. The genotype G3 grown in either one or all of the three environments exhibits worthy performance and stability for most of the tested quality traits. The crossing of this genotype with high yield genotypes could produce cultivars with sufficient quality and marketability. PMID- 27386102 TI - Quality changes and freezing time prediction during freezing and thawing of ginger. AB - Effects of different freezing rates and four different thawing methods on chemical composition, microstructure, and color of ginger were investigated. Computer simulation for predicting the freezing time of cylindrical ginger for two different freezing methods (slow and fast) was done using ANSYS ((r)) Multiphysics. Different freezing rates (slow and fast) and thawing methods significantly (P < 0.05) affected the color and composition of essential oil in ginger. Fresh ginger was found to contain 3.60% gingerol and 18.30% zingerone. A maximum yield of 7.43% gingerol was obtained when slow frozen gingers when thawed by infrared method. Maximum zingerone content of 38.30% was achieved by thawing slow frozen gingers using infrared-microwave method. Microscopic examination revealed that structural damage was more pronounced in slow frozen gingers than fast frozen gingers. Simulated freezing curves were in good agreement with experimental measurements (r = 0.97 for slow freezing and r = 0.92 for fast freezing). Slow freezing damaged ginger's cellular structure. Data obtained will be helpful in selecting appropriate thawing method to increase desirable essential oil components in ginger. Computer simulation for predicting freezing time may help in developing proper storage system of ginger. PMID- 27386103 TI - Effect of conventional milling on the nutritional value and antioxidant capacity of wheat types common in Ethiopia and a recovery attempt with bran supplementation in bread. AB - The effect of wheat flour refined milling on nutritional and antioxidant quality of hard and soft grown in Ethiopia was evaluated. Bread was prepared with the supplementation of the white wheat flour with different levels (0%, 10%, 20%, and 25%) of wheat bran. Whole (100% extraction) and white wheat (68% extraction) flours were analyzed for proximates, minerals, and antioxidants. Results indicated that at a low extraction rate (68%), the protein, fat, fiber, ash, iron, zinc, phosphorous, and antioxidant contents of the samples significantly (P < 0.05) decreased by milling. The TPC (total phenolic content) of the white wheat flours, which ranged from 3.34 to 3.49 mg GAE (gallic acid equivalent)/g, was significantly (P < 0.005) lower than those of the whole wheat flours, whose TPC ranged from 7.66 to 8.20 GAE/g). At 50 mg/mL, the DPPH (2-diphenyl-1 picrylhydrazyl) scavenging effect of the wheat extracts decreased in the order of soft whole, hard whole, soft white, and hard white wheat flour, which was 90.39, 89.89, 75.80, and 57.57%, respectively. Moreover, the proximate and mineral contents of the bran-supplemented breads increased significantly (P < 0.05) with the bran level of the bread, and the highest values (protein, 12.0 g/100 g; fat, 2.6 g/100 g; fiber, 2.5 g/100 g; ash, 3.3 g/100 g; iron, 4.8 mg/100 g and zinc, 2.33 mg/100 g) were found in 25% bran supplemented bread. The sensory evaluation of bread showed that all the supplementation levels had a mean score above 4 for all preferences on a 7- point hedonic scale. The results indicated that refined milling at 68% extraction significantly reduces the nutritional and antioxidant activity of the wheat flours. Bread of good nutritional and sensory qualities can be produced from 10% and 20% bran supplementations. PMID- 27386104 TI - Procedure of brewing alcohol as a staple food: case study of the fermented cereal liquor "Parshot" as a staple food in Dirashe special woreda, southern Ethiopia. AB - For most brews, alcohol fermentation and lactic fermentation take place simultaneously during the brewing process, and alcohol fermentation can progress smoothly because the propagation of various microorganisms is prevented by lactic fermentation. It is not necessary to cause lactic fermentation with a thing generated naturally and intentionally. The people living in the Dirashe area in southern Ethiopia drink three types of alcoholic beverages that are prepared from cereals. From these alcoholic beverages, parshot is prepared by the addition of plant leaves for lactic fermentation and nech chaka by adding cereal powder for lactic fermentation before alcohol fermentation. People living in the Dirashe area partake of parshot as part of their staple diet. The brewing process used for parshot and a food culture with alcoholic beverages as parts of the staple diet are rare worldwide. This article discusses the significance of using lactic fermentation before alcoholic fermentation and focuses on lactic fermentation in the brewing methods used for the three kinds of alcoholic beverages consumed in the Dirashe area. We initially observed the brewing process and obtained information about the process from the people in that area. Next, we determined the pH and analyzed the lactic acid (g/100 g) and ethanol (g/100 g) content during lactic fermentation of parshot and nech chaka; the ethyl acetate (mg/100 g) and volatile base nitrogen (mg/100 g) content during this period was also analyzed. In addition, we compared the ethanol (g/100 g) content of all three kinds of alcoholic beverages after completion of brewing. The results showed that it was possible to consume large quantities of these alcoholic beverages because of the use of lactic fermentation before alcoholic fermentation, which improved the safety and preservation characteristics of the beverages by preventing the propagation of various microorganisms, improving flavor, and controlling the alcohol level. PMID- 27386105 TI - Use of the wetting method on cassava flour in three konzo villages in Mozambique reduces cyanide intake and may prevent konzo in future droughts. AB - Konzo is an irreversible paralysis of the legs that occurs mainly in children and young women associated with large cyanide intake from bitter cassava coupled with malnutrition. In East Africa outbreaks occur during drought, when cassava plants produce much more cyanogens than normal. A wetting method that removes cyanogens from cassava flour was taught to the women of three konzo villages in Mozambique, to prevent sporadic konzo and konzo outbreaks in the next drought. The intervention was in three villages with 72 konzo cases and mean konzo prevalence of 1.2%. The percentage of children with high (>350 MUmol/L) urinary thiocyanate content and at risk of contracting konzo in Cava, Acordos de Lusaka, and Mujocojo reduced from 52, 10, and 6 at baseline to 17, 0, and 4 at conclusion of the intervention. Cassava flour showed large reductions in total cyanide over the intervention. The percentage of households using the wetting method was 30-40% in Acordos de Lusaka and Mujocojo and less in Cava. If the wetting method is used extensively by households during drought it should prevent konzo outbreaks and chronic cyanide intoxication. We recommend that the wetting method be taught in all konzo areas in East Africa. PMID- 27386106 TI - Impact of type of child growth intervention program on caregivers' child feeding knowledge and practices: a comparative study in Ga West Municipality, Ghana. AB - Community-based growth promotion (CBGP) delivered by community volunteers aims at enhancing the traditional growth monitoring and promotion (GMP) program delivered by community health nurses through the promotion of optimum infant and young child feeding (IYCF) leading to improved child growth. This study compared IYCF knowledge and practices among caregiver-child pairs (0-24 months) receiving child welfare services from CBGP (n = 124) and GMP (n = 108) programs. Semistructured questionnaires were used to interview caregivers on IYCF knowledge/practices and validated food frequency questionnaire used to record infants' food intakes. Group differences were determined using Chi-square and independent samples t tests (P < 0.05; 95% confidence interval [CI]). Mean IYCF knowledge scores were similar (CBGP: 10.84 +/- 1.69 vs. GMP: 10.23 +/- 1.38, P = 0.062). However, more CBGP caregivers (17%) were highly knowledgeable than their GMP counterparts (5%) (P = 0.011). Early breastfeeding initiation (CBGP: 54% vs. GMP: 28%, P < 0.0001), exclusive breastfeeding (CBGP: 73% vs. GMP: 56%, P = 0.001), and timely complementary feeding (CBGP: 72% vs. GMP: 49%, P = 0.014) were reportedly higher among CBGP caregivers. Underweight was 11% (CBGP: 8% vs. GMP: 14%, P = 0.154). Mean dietary diversity scores (10 food groups) were similar (CBGP: 4.49 +/- 1.89 vs. GMP: 3.87 +/- 1.89, P = 0.057) but more CBGP caregivers (77%) achieved minimum dietary diversity than their GMP counterparts (61%) (P = 0.035). Few caregivers achieved minimum meal frequency (CBGP: 31% vs. GMP: 29%, P = 0.486) and minimum acceptable diet (CBGP: 23% vs. GMP: 21%, P = 0.464) indicators. Number of children under 5 years owned by caregiver (adjusted odds ratio [AOR]: 0.405; 95% CI: 1.13-78.53, P = 0.038), her educational level (AOR: 0.112; 95% CI: 0.02-0.90, P = 0.040), and IYCF knowledge (AOR: 0.140; 95% CI: 0.03-0.79, P = 0.026) significantly predicted optimum child feeding. Nutrition education on optimum complementary feeding and birth spacing strategies should intensify. PMID- 27386107 TI - Rheological, baking, and sensory properties of composite bread dough with breadfruit (Artocarpus communis Forst) and wheat flours. AB - The rheological (Pasting, farinograph, and alveograph) properties of wheat flour (WF) replaced with breadfruit four (05-40%) was analyzed. Baking and sensory qualities of the resulting bread were evaluated. Differences in baking properties of loaves produced under laboratory and industrial conditions were analyzed with t-test, whereas ANOVA was used for other analyses. Peak and final viscosities in the composite blends (CB) ranged from 109.20 to 114.06 RVU and 111.86 to 134.40 RVU, respectively. Dough stability decreased from 9.15 to 0.78 min, whereas farinograph water absorption increased 59.7-65.9%. Alveograph curve configuration ratio increased from 1.27 to 7.39, whereas specific volume (Spv) of the loaves decreased from 2.96 to 1.32 cm(3)/g. The Spv of WF loaves were not significantly different (P > 0.05) from that of the 5% CB, whereas production conditions had no significant effects on absorbed water (t = 0.532, df = 18 P = 0.3005), weight loss during baking (t = 0.865, df = 18, P = 0.199), and Spv (t = 0.828, df = 14.17, P = 0.211). The sensory qualities of the 5% blend were not significantly different from the WF. PMID- 27386108 TI - Rapid detection of bovine adipose tissue using lateral flow strip assay. AB - Currently no rapid immunoassays are developed to identify the species content of fat tissue in mixtures. We report a simple protocol enabling the effective detection of bovine fat in highly processed materials using a lateral flow (LF) immunoassay which targets a ruminant-specific muscle protein. A portion (50 gm) of muscle-free fat samples was rendered to separate the molten fat from the proteinaceous residue, then soluble proteins were extracted from the solid residue with 0.5 mol/L NaCl for the LF analysis. The assay could detect 2% bovine fat-in-pork fat, 1% bovine fat-in-porcine meat-and-bone meal, and 0.5% bovine fat in-soy meal mixtures. Rendered bovine fat could be detected up to 213 degrees C. These results demonstrate that low levels of bovine fat tissue can be detected in processed materials using an immunoassay based on the presence of the muscle protein which serves as a species marker in the fat tissue. PMID- 27386109 TI - Antioxidant activity and phenolic profiles of the wild currant Ribes magellanicum from Chilean and Argentinean Patagonia. AB - The Patagonian currant Ribes magellanicum is highly valued due to its pleasant flavor and sweet taste. The aim of this study was to characterize its constituents and to assess their antioxidant and cytoprotective properties. For the fruit phenolic-enriched extract (PEE), total phenolics (TP), total flavonoids (TF), and antioxidant activity (DPPH, Ferric reducing antioxidant power (FRAP), and Trolox equivalent antioxidant activity (TEAC)) were determined. Argentinean samples presented better activity in the DPPH and FRAP assays. Best cytoprotection against oxidative stress induced by H2O2 in AGS cells was found in one Argentinean sample at 500 MUg mL(-1) (65.7%). HPLC MS/MS analysis allowed the tentative identification of 59 constituents, including eight anthocyanins, 11 conjugates of caffeic-, ferulic-, and coumaric acid, and 38 flavonoids, most of them quercetin and kaempferol derivatives. Argentinean samples showed a more complex pattern of anthocyanins, hydroxycinnamic acids (HCA), and flavonoids. Cyanidin rhamnoside hexoside and cyanidin hexoside were the main anthocyanins, accounting for 35 and 55% for the Argentinean and 60 and 27% for the ripe Chilean fruits. HCA content was about three times higher in Argentinean samples. The phenolic profiles of Chilean and Argentinean Ribes magellanicum show remarkable differences in chemical composition with higher HCA and flavonoid content in Argentinean samples. PMID- 27386110 TI - A study on the physicochemical parameters for Penicillium expansum growth and patulin production: effect of temperature, pH, and water activity. AB - Penicillium expansum is among the most ubiquitous fungi disseminated worldwide, that could threaten the fruit sector by secreting patulin, a toxic secondary metabolite. Nevertheless, we lack sufficient data regarding the growth and the toxigenesis conditions of this species. This work enables a clear differentiation between the favorable conditions to the P. expansum growth and those promising for patulin production. A mathematical model allowing the estimation of the P. expansum growth rate according to temperature, a W, and pH, was also developed. An optimal growth rate of 0.92 cm/day was predicted at 24 degrees C with pH level of 5.1 and high a W level of 0.99. The model's predictive capability was tested successfully on artificial contaminated apples. This model could be exploited by apple growers and the industrialists of fruit juices in order to predict the development of P. expansum during storage and apple processing. PMID- 27386111 TI - Quality attributes of sweet potato flour as influenced by variety, pretreatment and drying method. AB - The effect of pretreatment methods (soaking in water, potassium metabisulphite solution, and blanching) and drying methods (sun and oven) on some quality attributes of flour from ten varieties of sweet potato roots were investigated. The quality attributes determined were chemical composition and functional properties. Data obtained were subjected to descriptive statistics, multivariate analysis of variance, and Pearson's correlation. The range of values for properties of sweet potato flour were: moisture (8.06-12.86 +/- 1.13%), starch (55.76-83.65 +/- 6.82%), amylose (10.06-21.26 +/- 3.92%), total sugar (22.39 125.46 +/- 24.68 MUg/mg), water absorption capacity (140-280 +/- 26), water solubility (6.89-26.18 +/- 3.80), swelling power (1.66-5.00 +/- 0.50), peak viscosity (24.50-260.92 +/- 52.61 RVU), trough (7.08-145.83 +/- 34.48 RVU), breakdown viscosity (11.00-125.33 RVU), final viscosity (10.21-225.50 +/- 60.55 RVU), setback viscosity (3.04-92.21 RVU), peak time (6.07-9.06 min) and pasting temperature (69.8-81.3 degrees C). Variety had a significant (P < 0.001) effect on all the attributes of sweet potato flour. Pretreatment did not significantly (P > 0.05) affect moisture, fat and lightness (L*). Drying method did not significantly (P > 0.05) affect fiber and L*. The interactive effect of variety, pretreatment and drying method had a significant (P < 0.001) effect on all the attributes except fat and fiber. Total sugar correlated significantly (P < 0.01) with water solubility (r = 0.88) of the flour samples. Variety was a dominant factor influencing attributes of sweet potato flour and so should be targeted at specific end uses. PMID- 27386112 TI - Effect of hydrocolloids and emulsifiers on the shelf-life of composite cassava maize-wheat bread after storage. AB - The objective of this study was to evaluate the effect of hydrocolloids and/or emulsifiers on the shelf-life of composite cassava-maize-wheat (ratio 40:10:50) reference bread during storage. Added hydrocolloids were carboxymethylcellulose (CMC) and high methoxyl pectin (HM pectin) at a 3% level (w/w) and/or the emulsifiers diacetyl tartaric acid esters of monoglycerides (DATEM), lecithin (LC), and monoglycerides (MG) at a 0.3% level (w/w). After 4 days of storage, composite breads with MG had comparatively lower crumb moisture while crumb density was similar in all breads. The reference bread crumb firmness was 33.4 N, which was reduced with an addition of DATEM (23.0 N), MG (29.8 N), CMC (24.6 N) or HM pectin (22.4 N). However, the CMC/DATEM, CMC/LC, and HM pectin/DATEM combinations further reduced crumb firmness to <20.0 N. The melting peak temperature was increased from 52 C to between 53.0 C and 57.0 C with added hydrocolloids and/or emulsifiers. The melting enthalpy of the retrograded amylopectin was lower in composite bread with hydrocolloids and emulsifiers, 6.7 11.0 J/g compared to 20.0 J/g for the reference bread. These results show that emulsifiers in combination with hydrocolloids can improve the quality and extend the shelf-life of composite cassava-maize-wheat breads. PMID- 27386113 TI - Effects of processing on carbendazim residue in Pleurotus ostreatus. AB - Samples of Pleurotus ostreatus were exposed to fungicide carbendazim to study the effect of processing on the residues. In most cases, processing operations led to a significant decrease in residue levels in the finished products, particularly through washing, drying, and cooking processes. The results indicated that rinsing under running tap water led to more than 70.30% loss in carbendazim residues. When dried under sunlight could remove more than 70.30% residues. There was a 63.90-97.14% reduction after steaming, with processing time extending, the removal rates increased especially for lower initial residue level samples. The residue was almost completely removed by frying combined with microwave heating. Furthermore, boiling the mushrooms reduced the residue in the mushroom and no carbendazim residues were determined in the broth. PMID- 27386114 TI - Effect of selected spices on chemical and sensory markers in fortified rye buckwheat cakes. AB - The aim of this study was to find out the effect of selected spices on chemical and sensorial markers in cakes formulated on rye and light buckwheat flour fortified with spices. Among collection of spices, rye-buckwheat cakes fortified individually with cloves, nutmeg, allspice, cinnamon, vanilla, and spice mix revealed the highest sensory characteristics and overall quality. Cakes fortified with cloves, allspice, and spice mix showed the highest antioxidant capacity, total phenolics, rutin, and almost threefold higher available lysine contents. The reduced furosine content as well as free and total fluorescent intermediatory compounds were observed as compared to nonfortified cakes. The FAST index was significantly lowered in all cakes enriched with spices, especially with cloves, allspice, and mix. In contrast, browning index increased in compare to cakes without spices. It can be suggested that clove, allspice, vanilla, and spice mix should be used for production of safety and good quality cakes. PMID- 27386116 TI - Clinical impact of increasing left ventricular pacing output in cardiac resynchronization therapy - the new optimization strategy. AB - We report a patient who did not improve after standard optimization of atrioventricular and intraventricular pacing timing, but showed response to cardiac resynchronization therapy (CRT) after increasing left ventricular (LV) pacing output. Increasing LV pacing output is one of the useful optimization methods for CRT nonresponder. PMID- 27386117 TI - Torsion of left main bronchus during general anesthesia for posterior instrumented spinal fusion. AB - Pulmonary function tests such as flow-volume loops and reconstructive radiological imaging may aid the detection of large airway obstruction prior to corrective surgery for severe scoliosis. Intraoperative use of halo-gravity traction may help to reduce the severity of the scoliosis, and thus the extrinsic compression or torsion of the airways. PMID- 27386115 TI - International pooled study on diet and bladder cancer: the bladder cancer, epidemiology and nutritional determinants (BLEND) study: design and baseline characteristics. AB - BACKGROUND: In 2012, more than 400,000 urinary bladder cancer cases occurred worldwide, making it the 7(th) most common type of cancer. Although many previous studies focused on the relationship between diet and bladder cancer, the evidence related to specific food items or nutrients that could be involved in the development of bladder cancer remains inconclusive. Dietary components can either be, or be activated into, potential carcinogens through metabolism, or act to prevent carcinogen damage. METHODS/DESIGN: The BLadder cancer, Epidemiology and Nutritional Determinants (BLEND) study was set up with the purpose of collecting individual patient data from observational studies on diet and bladder cancer. In total, data from 11,261 bladder cancer cases and 675,532 non-cases from 18 case control and 6 cohort studies from all over the world were included with the aim to investigate the association between individual food items, nutrients and dietary patterns and risk of developing bladder cancer. DISCUSSION: The substantial number of cases included in this study will enable us to provide evidence with large statistical power, for dietary recommendations on the prevention of bladder cancer. PMID- 27386118 TI - Congenital cataract associated with persistent hyperplastic primary vitreous and persistent tunica vasculosa lentis in a sambar deer (Rusa unicolor) - clinical, ultrasonographic, and histological findings. AB - Ultrasonography suggested the diagnosis of cataract associated with persistent fetal intraocular vasculature in a 26-day-old sambar deer. The deer was ill and died despite intense critical care. Globes were removed. Histological characteristics of persistent fetal vasculature and secondary cataract are reported expanding the knowledge of ophthalmic disorders in wild ungulates. PMID- 27386120 TI - Late prostatic metastasis of an uveal melanoma in a miniature Schnauzer dog. AB - This manuscript describes a previously unreported clinical case of canine uveal melanoma in a miniature Schnauzer dog with an unusual location of metastasis (prostate) and delayed occurrence (3 years after primary tumor diagnosis and enucleation). Immunohistochemical labeling of both tumors with Melan A, Ki-67, and c-kit added some valuable information. PMID- 27386119 TI - Soft tissue swelling in children: case report, differential diagnosis, and diagnostic delay. AB - A general practitioner faces regularly soft tissue swelling in otherwise healthy children. Delay in diagnosis of soft tissue malignancies is often due to asymptomatic nature and the unfamiliarity with the age-dependent differential diagnosis. Hence, an accurate knowledge is important to prevent important delay in diagnosis of potential malignancies. PMID- 27386121 TI - Case report: successful retreatment of hepatitis C genotype 1b infection with sofosbuvir + simeprevir in a patient with cirrhosis who had prior virologic relapse after treatment with daclatasvir and asunaprevir. AB - There is currently minimal clinical experience regarding retreatment options for patients failing direct-acting antiviral combination regimens. Here, we report the outcomes of a HCV genotype 1b-infected patient with virologic failure following treatment with daclatasvir and asunaprevir, who was successfully retreated with sofosbuvir plus simeprevir. PMID- 27386122 TI - Immunoglobulin G4-related disease: a rare disease with an unusual presentation. AB - IgG4-RD can also present in the skeletal muscle, mimicking several other diseases. It is unusual for this relatively new classification of diseases to present in the muscles and can be mistakenly diagnosed as other autoimmune diseases rendering a delay in the appropriate management and progression of the disease. PMID- 27386123 TI - Choledocholithiases in a child with Hemoglobin Evans [alpha2 62(E11) Val->Met]. AB - We present the first description of choledocholithiases in a 10-year-old boy with Hemoglobin Evans. Although biliary stones are much less common in children than in adults, epigastric pain in children with known hemolytic status should alert the physician to the possibility of biliary colic. PMID- 27386124 TI - Managing adipsic diabetes insipidus following anterior communicating artery aneurysm in a subtropical climate. AB - Diabetes insipidus without perception of thirst, as may follow an anterior communicating artery aneurysm, requires prescription of fluid intake as well as desmopressin. The management goal of maintaining a normal serum sodium is rendered more challenging in a humid subtropical environment, where insensible losses are higher. PMID- 27386125 TI - Prenatal diagnosis of the rare association of common arterial trunk and double aortic arch. AB - Common arterial trunk with associated double aortic arch is a very rare constellation of congenital heart disease. Prenatal diagnosis allows for surgical repair prior to development of respiratory morbidity, which is otherwise described in all cases with this association. PMID- 27386126 TI - Thrombocytopenia-associated multiorgan failure occurring in an infant at the onset of type 1 diabetes successfully treated with fresh frozen plasma. AB - TAMOF is a devastating microangiopathy that can occur in association with the new onset of T1DM, and should be considered with the onset of thrombocytopenia, renal failure, and raised LDH. Treatment with fresh frozen plasma should be considered as a first-line option in such cases prior to plasma exchange. PMID- 27386127 TI - Infantile spasms with periventricular nodular heterotopia, unbalanced chromosomal translocation 3p26.2 -10p15.1 and 6q22.31 duplication. AB - Patients presenting with infantile spasms, dysmorphic features, and periventricular nodular heterotopia may benefit from genetic copy number variation microarray, or whole-exome sequencing to identify candidate genes. This will allow personalized diagnosis and prognostication and the eventual understanding of single and combined gene functions in brain health and disease. PMID- 27386128 TI - Spontaneous bilateral patellar tendon rupture: case report and review of fluoroquinolone-induced tendinopathy. AB - The present case emphasizes the importance of adhering to strict indications when prescribing fluoroquinolones. Although rare, drug-induced tendinopathy is not confined to fluoroquinolones. The patient's and physician's awareness should be increased to reduce fluoroquinolones-associated morbidity, particularly in patients with previously described risk factors. PMID- 27386129 TI - Monochorionic-diamniotic discordant growth in a twin pregnancy with one fetus affected by Ebstein's anomaly of tricuspid leaflets. AB - Our patient was diagnosed as having discordant twin growth with Ebstein's anomaly in the larger fetus. Cardiac function was deteriorated in accordance with progression of gestational age. Our observation indicated cardiac failure of the larger fetus. The most important issue in this situation is management of the timing of delivery. PMID- 27386130 TI - A transient increase and subsequent sharp decrease of chemo-refractory liver metastasized uterine cervical small cell carcinoma to autologous formalin-fixed tumor vaccine plus anti-PD-1 antibody. AB - Uterine cervical small cell carcinoma is rare and aggressive with no standardized therapy. A patient bearing the advanced chemo-refractory carcinoma, treated with a tumor vaccine combined with 1 mg/kg of pembrolizumab, showed a transient increase and subsequent sharp decrease of the liver-metastasized lesion to less than half its maximum diameter. PMID- 27386131 TI - Kasabach-Merritt phenomenon and prenatal counseling: a case series. AB - Kasabach-Merritt phenomenon can be encountered in the perinatal period. No consensus exists regarding prenatal management. We report one prenatal case leading to therapeutic abortion and one neonatal case, successfully treated by a multimodal therapy. Prenatal counseling should include the possibility of neonatal multimodal treatment that can lead to favorable outcomes. PMID- 27386132 TI - Whole exome sequencing reveals EP300 mutation in mildly affected female: expansion of the spectrum. AB - Rubinstein-Taybi syndrome is associated with intellectual and physical features. CREBBP and EP300 are causative. Few cases of EP300 mutations are reported. We report a case with mild features of RSTS and EP300 mutation on exome sequencing. This illustrates the utility of exome sequencing to expand every genetic phenotype. PMID- 27386133 TI - Acute complete uterine inversion after controlled cord traction of placenta following vaginal delivery: a case report. AB - Early recognition and active management of the third stage of labor will reduce the risks associated with uterine inversion. All staff members in the maternal unit should be updated with Green-Top guidelines No. 52 and be appropriately trained in the PROMPT course to provide a standardized approach in obstetric emergencies. PMID- 27386134 TI - Diagnosis of congenital von Willebrand disease during a preoperative assessment in a multiple myeloma patient without bleeding history. AB - We report a rare case of type 2M von Willebrand disease diagnosed in an elderly multiple myeloma patient who had no personal and family bleeding history. This case report emphasis the importance to not systematically exclude a congenital vWD in adult patients when coagulation screening tests indicate toward a vWD. PMID- 27386135 TI - Kussmaul's sign and rapid X-Y descents in constrictive pericarditis. AB - Right-sided heart failure is not uncommon. A careful jugular venous examination looking for the distinct Kussmaul's sign and rapid X-Y descents, which are highly indicative of constrictive pericarditis, is markedly helpful in guiding the correct diagnosis and proper management. PMID- 27386136 TI - Should the clinician do the tests for benign paroxysmal positional vertigo even in the presence of spontaneous nystagmus at primary gaze? AB - Different balance problems may occur in the same patient simultaneously, and the other problem may be overlooked if the clinician does not pay much attention. Spontaneous nystagmus of Meniere's disease and positional nystagmus of posterior canal BPPV in the same patient is presented. Positional tests must always be considered even in the presence of spontaneous nystagmus. PMID- 27386137 TI - Each worm to his taste: some prefer to eat nettles - a giant gastric phytobezoar. AB - Nettle consumption, as well as persimmon, orange, coconut etc. can lead to phytobezoar formation. Coke and cellulase-resistant phytobezoars should be removed either endoscopically or surgically, depending on their dimensions. The treatment of choice for giant phytobezoars (more than 10 cm) is gastrotomy. PMID- 27386138 TI - Analyzing subcomponents of affective dysregulation in borderline personality disorder in comparison to other clinical groups using multiple e-diary datasets. AB - BACKGROUND: Affective dysregulation is widely regarded as being the core problem in patients with borderline personality disorder (BPD). Moreover, BPD is the disorder mainly associated with affective dysregulation. However, the empirical confirmation of the specificity of affective dysregulation for BPD is still pending. We used a validated approach from basic affective science that allows for simultaneously analyzing three interdependent components of affective dysregulation that are disturbed in patients with BPD: homebase, variability, and attractor strength (return to baseline). METHODS: We applied two types of multilevel models on two e-diary datasets to investigate group differences regarding three subcomponents between BPD patients (n = 43; n = 51) and patients with posttraumatic stress disorder (PTSD; n = 28) and those with bulimia nervosa (BN; n = 20) as clinical control groups in dataset 1, and patients with panic disorder (PD; n = 26) and those with major depression (MD; n = 25) as clinical control groups in dataset 2. In addition, healthy controls (n = 28; n = 40) were included in the analyses. In both studies, e-diaries were used to repeatedly collect data about affective experiences during participants' daily lives. In study 1 a high-frequency sampling strategy with assessments in 15 min-intervals over 24 h was applied, whereas the assessments occurred every waking hour over 48 h in study 2. The local ethics committees approved both studies, and all participants provided written informed consent. RESULTS: In contradiction to our hypotheses, BPD patients did not consistently show altered affective dysregulation compared to the clinical patient groups. The only differences in affective dynamics in BPD patients emerged with regard to one of three subcomponents, affective homebase. However, these results were not even consistent. Conversely, comparing the patients to healthy controls revealed a pattern of more negative affective homebases, higher levels of affective variability, and (partially) reduced returns to baseline in the patient groups. CONCLUSIONS: Our results indicate that affective dysregulation constitutes a transdiagnostic mechanism that manifests in similar ways in several different mental disorders. We point out promising prospects that might help to elucidate the common and distinctive mechanisms that underlie several different disorders and that should be addressed in future studies. PMID- 27386139 TI - No sweat: African American adolescent girls' opinions of hairstyle choices and physical activity. AB - BACKGROUND: Obesity prevalence is higher among African American adolescent (AAA) girls than among non-black girls. Lower levels of physical activity (PA) likely contribute to this disparity; this may be impacted by hairstyle concerns. METHODS: In 2011, focus groups were conducted with AAA girls 14-17 years old (n = 36) in Michigan (n = 9), California (n = 11), and Georgia (n = 16). Groups addressed perceptions of hairstyles, exercise, and relationships between the two. Groups were recorded, transcripts reviewed, and themes identified. Adolescents completed a standardized ethnic identity (EI) measure and a survey addressing demographics and PA. Linear regression was used to examine associations between self-reported activity and participants' characteristics. RESULTS: Four themes emerged: 1) between ages 8 and 15, when concerns about hairstyles began, participants changed from "juvenile" (natural) styles to "adult" (straightened) styles; 2) participants avoided getting wet or sweating during exercise because their straightened hair became "nappy;" 3) braids with extensions and natural styles were viewed as better for exercise but not very attractive; 4) participants almost universally selected long, straight hairstyles as most attractive. In Michigan and California, EI was positively associated with levels of PA (p < 0.05) and overall having extensions was also positively associated with levels of PA. CONCLUSIONS: A preference for straight hair may contribute to AAA girls avoiding certain activities due to concerns about sweat affecting their hair. Furthermore, EI and hairstyle choice appear to be associated with levels of PA for some participants. Efforts to increase AAA girls' PA may benefit from approaches that address hairstyle choices and EI. PMID- 27386140 TI - Efficacy and safety of warfarin in dialysis patients with atrial fibrillation: a systematic review and meta-analysis. AB - OBJECTIVE: To systematically review and meta-analyse the risk-benefit ratio of warfarin users compared with non-warfarin users in patients with atrial fibrillation (AF), who are undergoing dialysis. METHODS: We searched PubMed/MEDLINE, EMBASE, SCOPUS, Web of Science, Cochrane Library, grey literature, conference proceedings, trial registrations and also did handsearch. Cohort studies without language restrictions were included. Two investigators independently conducted a full abstraction of data, risk of bias and graded evidence. Effect estimates were pooled using random-effect models. MAIN OUTCOME MEASURE: All-cause mortality, total stroke/thromboembolism and bleeding complications. RESULTS: 14 studies included 37 349 dialysis patients with AF, of whom 12 529 (33.5%) were warfarin users. For all-cause mortality: adjusted HR=0.99 (95% CI 0.89 to 1.10; p=0.825), unadjusted risk ratio (RR)=1.00 (95% CI 0.96 to 1.04; p=0.847). For stroke/thromboembolism: adjusted HR=1.06 (95% CI 0.82 to 1.36; p=0.676), unadjusted incidence rate ratio (IRR)=1.23 (95% CI 0.94 to 1.61; p=0.133). For ischaemic stroke/transient ischaemic attack, adjusted HR=0.91 (95% CI 0.57 to 1.45; p=0.698), unadjusted IRR=1.16 (95% CI 0.84 to 1.62; p=0.370). For haemorrhagic stroke, adjusted HR=1.60 (95% CI 0.91 to 2.81; p=0.100), unadjusted IRR=1.48 (95% CI 0.92 to 2.36; p=0.102). Major bleeding was increased among warfarin users; adjusted HR=1.35 (95% CI 1.11 to 1.64; p=0.003) and unadjusted IRR=1.22 (95% CI 1.07 to 1.40; p=0.003). CONCLUSIONS: Among dialysis patients with AF, warfarin therapy was not associated with mortality and stroke/thromboembolism, but significantly increased the risk of major bleeding. More rigorous studies are essential to demonstrate the effect of warfarin for stroke prophylaxis in dialysis patients with AF. PMID- 27386142 TI - History of Research on Pharmacopuncture in Korea. AB - OBJECTIVES: This study introduces the history and types of Korean pharmacopuncture and reports trends of research on Korean pharmacopuncture. METHODS: Pharmacopuncture studies were searched from the first year of each search engine to 2014 by using seven domestic and foreign search databases. Selected studies were divided into the history of pharmacopuncture, kinds and features of pharmacopuncture, research types, and experimental and clinic studies and were then classified by year of publication, type of pharmacopuncture, disease, and topic. RESULTS: Pharmacopuncture can be classified into four large groups: meridian field pharmacopuncture (MFP), eight-principles pharmacopuncture (EPP), animal-based pharmacopuncture (ABP) and mountain- ginseng pharmacopuncture, which is a single-co mpound pharmacopuncture (SCP). The largest numbers of studies were reported from 1997 to 2006, after which the numbers decreased until 2014. Of experimental studies, 51.9%, 18.7%. 14.3%, 9% and 3.4% were on SCP, ABP, MFP, formula pharmacopuncture (FP), and EPP, respectively. Of clinical studies, 54.7%, 15.3%. 14.9% 10.0% and 1.5% were on ABP, MFP, EPP, SCP, and FP (1.5%), respectively. Among clinical studies, case reports and case series accounted for 76.5%, followed by randomized controlled trials (RCTs, 16.4%) and non-RCT (13.9%). Musculoskeletal diseases, toxicity and safety tests, anti-cancer effects, and nervous system diseases were mainly treated in experimental studies while musculoskeletal diseases, nervous system diseases, toxicity and safety tests, and autonomic nerve function tests were addressed in clinical studies. Bee venom (BV) was the most frequently-used pharmacopuncture in mechanism studies. Pharmacopuncture was mainly used to treat musculoskeletal diseases. CONCLUSION: Pharmacopuncture and studies of it have made great progress in Korea. Studies on BV pharmacopuncture and musculoskeletal diseases accounted for most of the studies reported during the review period. Research on the types of pharmacopuncture and diseases has to be expanded. Especially, studies on the use of MFP and EPP for treating patients with various diseases are needed. PMID- 27386141 TI - Antibacterial potency of different deposition methods of silver and copper containing diamond-like carbon coated polyethylene. AB - BACKGROUND: Antibacterial coatings of medical devices have been introduced as a promising approach to reduce the risk of infection. In this context, diamond-like carbon coated polyethylene (DLC-PE) can be enriched with bactericidal ions and gain antimicrobial potency. So far, influence of different deposition methods and ions on antimicrobial effects of DLC-PE is unclear. METHODS: We quantitatively determined the antimicrobial potency of different PE surfaces treated with direct ion implantation (II) or plasma immersion ion implantation (PIII) and doped with silver (Ag-DLC-PE) or copper (Cu-DLC-PE). Bacterial adhesion and planktonic growth of various strains of S. epidermidis were evaluated by quantification of bacterial growth as well as semiquantitatively by determining the grade of biofilm formation by scanning electron microscopy (SEM). Additionally silver release kinetics of PIII-samples were detected. RESULTS: (1) A significant (p < 0.05) antimicrobial effect on PE-surface could be found for Ag- and Cu-DLC-PE compared to untreated PE. (2) The antimicrobial effect of Cu was significantly lower compared to Ag (reduction of bacterial growth by 0.8 (Ag) and 0.3 (Cu) logarithmic (log)-levels). (3) PIII as a deposition method was more effective in providing antibacterial potency to PE-surfaces than II alone (reduction of bacterial growth by 2.2 (surface) and 1.1 (surrounding medium) log-levels of PIII compared to 1.2 (surface) and 0.6 (medium) log-levels of II). (4) Biofilm formation was more decreased on PIII-surfaces compared to II-surfaces. (5) A silver-concentration-dependent release was observed on PIII-samples. CONCLUSION: The results obtained in this study suggest that PIII as a deposition method and Ag-DLC-PE as a surface have high bactericidal effects. PMID- 27386143 TI - The History of Liquid Ear Acupuncture and the Current Scientific State of the Art. AB - This short review article presents a current overview of existing publications and scientific results regarding liquid (ear) acupuncture. The injection of liquids into defined acupuncture points of the ear is not a method commonly used in the Western world. The term liquid acupuncture has different definitions, which makes understanding each definition and differentiating one from the other difficult. General terms like pharmacopuncture, homeosiniatry, and liquid acupuncture, which all describe the method of injecting different kinds of drugs into a defined body acupuncture point, are used. This article presents the history of liquid acupuncture, as well as the current scientific state of the art, from the point of view of two European researchers. Some articles are discussed and a few practical examples are presented. PMID- 27386144 TI - Biosynthesized Platinum Nanoparticles Inhibit the Proliferation of Human Lung Cancer Cells in vitro and Delay the Growth of a Human Lung-Tumor Xenograft in vivo: -In vitro and in vivo Anticancer Activity of bio-Pt NPs. AB - OBJECTIVES: Lung cancer remains a deadly disease with unsatisfactory overall survival. Cisplatin, a standard platinum (Pt)-based chemotherapeutic agent, has the potential to inhibit the growth of lung cancer. Its use, however, is occasionally limited by severe organ toxicity. However, until now, no systematic study has been conducted to verify its efficacy with proper experimental support in vivo. Therefore, we examined whether biosynthesized Pt nanoparticles (NPs) inhibited human lung cancer in vitro and in vivo to validate their use in alternative and complementary medicine. METHODS: We evaluated the in vitro and the in vivo anticancer efficiencies of biosynthesized Pt NPs in a subcutaneous xenograft model with A549 cells. Severe combined immune deficient mice (SCID) were divided into four groups: group 1 being the vehicle control group and groups 2, 3 and 4 being the experimental groups. Once the tumor volume had reached 70 ? 75 mm(3), the progression profile of the tumor growth kinetics and the body weights of the mice were measured every week for 6 weeks after oral administration of Pt NPs. Doses of Pt NPs of 500, 1,000 and 2,000 mg/kg of body weight were administered to the experimental groups and a dose of honey was administered to the vehicle control group. The efficacy was quantified by using the delay in tumor growth following the administration of Pt NPs of A549 human lung-cancer xenografts growing in SCID mice. RESULTS: The in vitro cytotoxicity evaluation indicated that Pt NPs, in a dose-dependent manner, inhibited the growth of A549 cells, and the in vivo evaluation showed that Pt NPs at the mid and high doses effectively inhibited and delayed the growth of lung cancer in SCID mice. CONCLUSION: These findings confirm the antitumor properties of biosynthesized Pt NPs and suggest that they may be a cost-effective alternative for the treatment of patients with lung cancer. PMID- 27386145 TI - Cornu cervi pantotrichum Pharmacopuncture Solution Facilitate Hair Growth in C57BL/6 Mice. AB - OBJECTIVES: Cornu cervi pantotrichum (CCP) has been widely used in Korean and China, as an anti-fatigue, anti-aging, and tonic agent to enhance the functions of the reproductive and the immune systems. Because CCP has various growth factors that play important roles in the development of hair follicles, we examined whether CCP pharmacopuncture solution (CCPPS) was capable of promoting hair growth in an animal model. METHODS: One day after hair depilation, CCPPS were topically applied to the dorsal skin of C57BL/6 mice once a day for 15 days. Hair growth activity was evaluated by using macro- and microscopic observations. Dorsal skin tissues were stained with hematoxylin and eosin. Expressions of bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA), and fibroblast growth factor (FGF)-7 were examined by using immunohistochemical staining. A reverse transcription polymerase chain reaction (RT-PCR) analysis was also conducted to measure the messenger RNA (mRNA) expression of FGF-7. RESULTS: CCPPS induced more active hair growth than normal saline. Histologic analysis showed enlargement of the dermal papilla, elongation of the hair shaft, and expansion of hair thickness in CCPPS treated mice, indicating that CCPPS effectively induced the development of anagen. CCPPS treatment markedly increased the expressions of BrdU and PCNA in the hair follicles of C57BL/6 mice. In addition, CCPPS up regulated the expression of FGF-7, which plays an important role in the development of hair follicles. CONCLUSION: These results reveal that CCPPS facilitates hair re-growth by proliferation of hair follicular cells and up regulation of FGF-7 and suggest that CCPPS can potentially be applied as an alternative treatment for patients with alopecia. PMID- 27386146 TI - Inductions of Caspase-, MAPK- and ROS-dependent Apoptosis and Chemotherapeutic Effects Caused by an Ethanol Extract of Scutellaria barbata D. Don in Human Gastric Adenocarcinom Cells. AB - OBJECTIVES: The crude extracts of Scutellaria barbata D. Don (SB) have traditionally demonstrated inhibitory effects on numerous human cancers both in vitro and in vivo. Gastric cancer is one of the most common types of cancer on world. The authors investigated the effects of an ethanol extract of Scutellaria barbata D. Don (ESB) on the growth and survival of MKN-45 cells (a human gastric adenocarcinoma cell line). METHODS: The MKN-45 cells were treated with different concentrations of ESB, and cell death was examined using an MTT (3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Analyses of sub-G1 peaks, caspase-3 and -9 activities, and mitochondrial membrane depolarizations were conducted to determine the anti-cancer effects of SB on MKN-45 cells. Also, intracellular reactive oxygen species (ROS) generation was investigated. RESULTS: ESB inhibited the growth of MKN-45 cells, caused cell cycle arrest, and increased the sub-G1 population. In addition, ESB markedly increased mitochondrial membrane depolarization and the activities of caspase-3 and -9. ESB exerted anti proliferative effects on MKN-45 cells by modulating the mitogen-activated protein kinase (MAPK) signaling pathway and by increasing the generation of ROS. Furthermore, combinations of anti-cancer drugs plus ESB suppressed cell growth more than treatments with an agent or ESB, and this was especially true for cisplatin, etoposide, and doxorubicin. CONCLUSION: ESB has a dose-dependent cytotoxic effect on MKN-45 cells and this is closely associated with the induction of apoptosis. ESB-induced apoptosis is mediated by mitochondria- , caspase- and MAPK dependent pathways. In addition, ESB enhances ROS generation and increases the chemosensitivity of MKN-45 cells. These results suggest that treatment with ESB can inhibit the proliferation and promote the apoptosis of human gastric adenocarcinoma cells by modulating the caspase-, MAPK- and ROS dependent pathway. PMID- 27386147 TI - Cinnamaldehyde Attenuates Cataractogenesis via Restoration of Hypertension and Oxidative Stress in Fructose-Fed Hypertensive rats. AB - OBJECTIVES: Several studies have revealed that systemic hypertension is strongly associated with cataractogenesis. However, the pathophysiology and treatment is often unclear. In this study, we evaluated the anti-cataractogenic effect of cinnamaldehyde (CA), a natural organic compound, in rats with fructose-induced hypertension. METHODS: The rats were divided into six groups. For six weeks, the normal group received a suspension of 0.5% carboxy methyl cellulose (10 mL/kg/day, p.o.) while five other groups received a 10% (w/v) fructose solution in their drinking water to induce hypertension. By the end of the third week hypertension had been induced in all the animals receiving fructose. From the beginning of the fourth week to the end of the sixth week, one of those five groups (control) continued to receive only 10% (w/v) fructose solution, one group (standard) received ramipril (1 mg/kg/day, p.o.) plus 10% (w/v) fructose solution, and three groups (experimental) received CA at doses of 20, 30, and 40 mg/kg/day p.o., plus 10% (w/v) fructose solution. Blood pressure was measured weekly using a non-invasive blood pressure apparatus. After six weeks, the animals were sacrificed, and the anti-cataractogenic effects on the eye lenses were evaluated. RESULTS: Administration of fructose elevated both the systolic and the diastolic blood pressures, which were significantly reduced by CA at all dose levels. In the control group, a significant increase in the malonaldehyde (MDA) level and decreases in the total protein, Ca(2+)adenosine triphosphate (ATP)ase activity, glutathione peroxidase, catalase, superoxide dismutase and glutathione levels, as compared to the normal group, were observed. Administration of CA at all doses significantly restored the enzymatic, non enzymatic, antioxidants, total protein, and Ca(2+)ATPase levels, but decreased the MDA level, as compared to the control group. CONCLUSION: The present study revealed that CA modulated the antioxidant parameters of the serum and lens homogenates in hypertension-induced cataractogenic animals. PMID- 27386148 TI - Vasorelaxation Study and Tri-Step Infrared Spectroscopy Analysis of Malaysian Local Herbs. AB - OBJECTIVES: The aim of this paper is to investigate the activities of Malaysian local herbs (Clinacanthus nutans Lindau, Strobilanthes crispus, Murdannia bracteata, Elephantopus scaber Linn., Pereskia bleo, Pereskia grandifolia Haw., Vernonia amygdalina, and Swietenia macrophylla King) for anti-hypertensive and vasorelaxant activity. An infrared (IR) macro-fingerprinting technique consisting of conventional fourier transform IR (FTIR), second-derivative IR (SD-IR), and two-dimensional correlation IR (2D-correlation IR) analyses were used to determine the main constituents and the fingerprints of the Malaysian local herbs. METHODS: The herbs were collected, ground into powder form, and then macerated by using three different solvents: distilled water, 50% ethanol, and 95% ethanol, respectively. The potentials of the extracts produced from these herbs for use as vasorelaxants were determined. Additionally, the fingerprints of these herbs were analyzed by using FTIR spectra, SD-IR spectra, and 2D correlation IR spectra in order to identify their main constituents and to provide useful information for future pharmacodynamics studies. RESULTS: Swietenia macrophylla King has the highest potential in terms of vasorelaxant activity, followed by Vernonia amygdalina, Pereskia bleo, Strobilanthes crispus, Elephantopus scaber Linn., Pereskia grandifolia Haw., Clinacanthus nutans Lindau, and Murdannia bracteata. The tri-step IR macro-fingerprint of the herbs revealed that most of them contained proteins. Pereskia bleo and Pereskia grandifolia Haw. were found to contain calcium oxalate while Swietenia macrophylla King was found to contain large amounts of flavonoids. CONCLUSION: The flavonoid content of the herbs affects their vasorelaxant activity, and the tri-step IR macro- fingerprint method can be used as an analytical tool to determine the activity of a herbal medicine in terms of its vasorelaxant effect. PMID- 27386149 TI - Study of Intravenous Single-Dose Toxicity Test of Bufonis venonum Pharmacopuncture in Sprague-Dawley Rats. AB - OBJECTIVES: Bufonis venonum (BV) is toad venom and is the dried, white secretions of the auricular and the skin glands of toads. This study was performed to evaluate the toxicity of intravenous injection of Bufonis venonum pharmacopuncture (BVP) through a single- dose test with sprague-dawley (SD) rats. METHODS: Twenty male and 20 female 6-week-old SD rats were injected intravenously in the caudal vein with BVP or normal saline. The animals were divided into four groups with five female and five male rats per group: the control group injected with normal saline, the low-dosage group injected with 0.1 mL/animal of BVP, the medium-dosage group injected with 0.5 mL/ animal of BVP and the high-dosage group injected with 1.0 mL/animal of BVP. We performed clinical observations every day and body weight measurements on days 3, 7 and 14 after the injection. We also conducted hematology, serum biochemistry, and histological observations immediately after the observation period. RESULTS: No mortalities were observed in any experimental group. Paleness occurred in the medium- and the high-dosage groups, and congestion on tails was observed in females in the medium- and the high-dosage groups. No significant changes in weight, hematology, serum biochemistry, and histological observations that could be attributed to the intravenous injection of BVP were observed in any experimental group. CONCLUSION: The lethal dose of intravenously-administered BVP in SD rats is over 1.0 mL/animal. PMID- 27386150 TI - Modulation of the Expression of the GABAA Receptor beta1 and beta3 Subunits by Pretreatment with Quercetin in the KA Model of Epilepsy in Mice: -The Effect of Quercetin on GABAA Receptor Beta Subunits. AB - OBJECTIVES: Quercetin is a flavonoid and an important dietary constituent of fruits and vegetables. In recent years, several pharmacological activities of quercetin, such as its neuroprotective activity and, more specifically, its anti convulsant effects in animal models of epilepsy, have been reported. This study evaluated the role of quercetin pretreatment on gene expression of gamma-amino butyric acid type A (GABAA) receptor beta subunits in kainic acid (KA)-induced seizures in mice. METHODS: The animals were divided into four groups: one saline group, one group in which seizures were induced by using KA (10 mg/kg) without quercetin pretreatment and two groups pretreated with quercetin (50 and 100 mg/kg) prior to seizures being induced by using KA. Next, the messenger ribonucleic acid (mRNA) levels of the GABAA receptor beta subunits in the hippocampus of each animal were assessed at 2 hours and 7 days after KA administration. Quantitative real-time polymerase chain reaction (RT-PCR) assay was used to detect mRNA content in hippocampal tissues. RESULTS: Pretreatments with quercetin at doses of 50 and 100 mg/kg prevented significant increases in the mRNA levels of the beta 1 and the beta 3 subunits of the GABAA receptor at 2 hours after KA injection. Pretreatment with quercetin (100 mg/kg) significantly inhibited beta 1 and beta 3 gene expression in the hippocampus at 7 days after KA injection. But, this inhibitory effect of quercetin at 50 mg/kg on the mRNA levels of the beta 3 subunit of the GABAA receptor was not observed at 7 days after KA administration. CONCLUSION: These results suggest that quercetin (100 mg/kg) modulates the expression of the GABAA receptor beta 1 and beta 3 subunits in the KA model of epilepsy, most likely to prevent compensatory responses. This may be related to the narrow therapeutic dose range for the anticonvulsant activities of quercetin. PMID- 27386153 TI - An siRNA-based method for efficient silencing of gene expression in mature brown adipocytes. AB - Brown adipose tissue is a promising therapeutic target for opposing obesity, glucose intolerance and insulin resistance. The ability to modulate gene expression in mature brown adipocytes is important to understand brown adipocyte function and delineate novel regulatory mechanisms of non-shivering thermogenesis. The aim of this study was to optimize a lipofection-based small interfering RNA (siRNA) transfection protocol for efficient silencing of gene expression in mature brown adipocytes. We determined that a critical parameter was to deliver the siRNA to mature adipocytes by reverse transfection, i.e. transfection of non-adherent cells. Using this protocol, we effectively knocked down both high- and low-abundance transcripts in a model of mature brown adipocytes (WT-1) as well as in primary mature mouse brown adipocytes. A functional consequence of the knockdown was confirmed by an attenuated increase in uncoupled respiration (thermogenesis) in response to beta-adrenergic stimulation of mature WT-1 brown adipocytes transfected with uncoupling protein 1 siRNA. Efficient gene silencing was also obtained in various mouse and human white adipocyte models (3T3-L1, primary mouse white adipocytes, hMADS) with the ability to undergo "browning." In summary, we report an easy and versatile reverse siRNA transfection protocol to achieve specific silencing of gene expression in various models of mature brown and browning-competent white adipocytes, including primary cells. PMID- 27386152 TI - Surgical injury induces local and distant adipose tissue browning. AB - The adipose organ, which comprises brown, white and beige adipocytes, possesses remarkable plasticity in response to feeding and cold exposure. The development of beige adipocytes in white adipose tissue (WAT), a process called browning, represents a promising route to treat metabolic disorders. While surgical procedures constantly traumatize adipose tissue, its impact on adipocyte phenotype remains to be established. Herein, we studied the effect of trauma on adipocyte phenotype one day after sham, incision control, or surgical injury to the left inguinal adipose compartment. Caloric restriction was used to control for surgery-associated body temperature changes and weight loss. We characterized the trauma-induced cellular and molecular changes in subcutaneous, visceral, interscapular, and perivascular adipose tissue using histology, immunohistochemistry, gene expression, and flow cytometry analysis. After one day, surgical trauma stimulated adipose tissue browning at the site of injury and, importantly, in the contralateral inguinal depot. Browning was not present after incision only, and was largely independent of surgery-associated body temperature and weight loss. Adipose trauma rapidly recruited monocytes to the injured site and promoted alternatively activated macrophages. Conversely, PDGF receptor-positive beige progenitors were reduced. In this study, we identify adipose trauma as an unexpected driver of selected local and remote adipose tissue browning, holding important implications for the biologic response to surgical injury. PMID- 27386151 TI - Fatty acid metabolism and the basis of brown adipose tissue function. AB - Obesity has reached epidemic proportions, leading to severe associated pathologies such as insulin resistance, cardiovascular disease, cancer and type 2 diabetes. Adipose tissue has become crucial due to its involvement in the pathogenesis of obesity-induced insulin resistance, and traditionally white adipose tissue has captured the most attention. However in the last decade the presence and activity of heat-generating brown adipose tissue (BAT) in adult humans has been rediscovered. BAT decreases with age and in obese and diabetic patients. It has thus attracted strong scientific interest, and any strategy to increase its mass or activity might lead to new therapeutic approaches to obesity and associated metabolic diseases. In this review we highlight the mechanisms of fatty acid uptake, trafficking and oxidation in brown fat thermogenesis. We focus on BAT's morphological and functional characteristics and fatty acid synthesis, storage, oxidation and use as a source of energy. PMID- 27386154 TI - Visfatin expression analysis in association with recruitment and activation of human and rodent brown and brite adipocytes. AB - Human brown adipocytes are able to burn fat and glucose and are now considered as a potential strategy to treat obesity, type 2 diabetes and metabolic disorders. Besides their thermogenic function, brown adipocytes are able to secrete adipokines. One of these is visfatin, a nicotinamide phosphoribosyltransferase involved in nicotinamide dinucleotide synthesis, which is known to participate in the synthesis of insulin by pancreatic beta cells. In a therapeutic context, it is of interest to establish whether a potential correlation exists between brown adipocyte activation and/or brite adipocyte recruitment, and adipokine expression. We analyzed visfatin expression, as a pre-requisite to its secretion, in rodent and human biopsies and cell models of brown/brite adipocytes. We found that visfatin was preferentially expressed in mature adipocytes and that this expression was higher in brown adipose tissue of rodents compared to other fat depots. However, using various rodent models we were unable to find any correlation between visfatin expression and brown or brite adipocyte activation or recruitment. Interestingly, the situation is different in humans where visfatin expression was found to be equivalent between white and brown or brite adipocytes in vivo and in vitro. In conclusion, visfatin can be considered only as a rodent brown adipocyte biomarker, independently of tissue activation. PMID- 27386155 TI - 14-3-3zeta: A numbers game in adipocyte function? AB - Molecular scaffolds are often viewed as passive signaling molecules that facilitate protein-protein interactions. However, new evidence gained from the use of loss-of-function or gain-of-function models is dispelling this notion. Our own recent discovery of 14-3-3zeta as an essential regulator of adipogenesis highlights the complex roles of this member of the 14-3-3 protein family. Depletion of the 14-3-3zeta isoform affected parallel pathways that drive adipocyte development, including pathways controlling the stability of key adipogenic transcription factors and cell cycle progression. Going beyond adipocyte differentiation, this study opens new avenues of research in the context of metabolism, as 14-3-3zeta binds to a variety of well-established metabolic proteins that harbor its canonical phosphorylation binding motifs. This suggests that 14-3-3zeta may contribute to key metabolic signaling pathways, such as those that facilitate glucose uptake and fatty acid metabolism. Herein, we discuss these novel areas of research, which will undoubtedly shed light onto novel roles of 14-3-3zeta, and perhaps its related family members, on glucose homeostasis. PMID- 27386157 TI - Morphogenetics in brown, beige and white fat development. AB - Brown and beige (or brite) fat cells are capable of evoking non-shivering thermogenesis in response to cold and beta-adrenergic stimulation. By metabolizing lipids and carbohydrate via uncoupled respiration these cells directly convert energy to heat. The discovery of brown and brown-like adipocytes in adult humans has reinvigorated interest in stimulating brown and beige fat development to combat the obesity epidemic. This review focuses on the role that cytoskeleton dynamics play in the regulation of adipocyte biology, specifically beige and brown fat development and how newly discovered adipogenic morphogens affect these processes. PMID- 27386156 TI - Adrenergic regulation of cellular plasticity in brown, beige/brite and white adipose tissues. AB - The discovery of brown adipose tissue in adult humans along with the recognition of adipocyte heterogeneity and plasticity of white fat depots has renewed the interest in targeting adipose tissue for therapeutic benefit. Adrenergic activation is a well-established means of recruiting catabolic adipocyte phenotypes in brown and white adipose tissues. In this article, we review mechanisms of brown adipocyte recruitment by the sympathetic nervous system and by direct beta-adrenergic receptor activation. We highlight the distinct modes of brown adipocyte recruitment in brown, beige/brite, and white adipose tissues, UCP1-independent thermogenesis, and potential non-thermogenic, metabolically beneficial effects of brown adipocytes. PMID- 27386159 TI - Exercise regulation of adipose tissue. AB - Exercise training results in adaptations to numerous organ systems and offers protection against metabolic disorders including obesity and type 2 diabetes, and recent reports suggest that adipose tissue may play a role in these beneficial effects of exercise on overall health. Multiple studies have investigated the effects of exercise training on both white adipose tissue (WAT) and brown adipose tissue (BAT), as well as the induction of beige adipocytes. Studies from both rodents and humans show that there are exercise training-induced changes in WAT including decreased cell size and lipid content, and increased mitochondrial activity. In rodents, exercise training causes an increased beiging of WAT. Whether exercise training causes a beiging of human scWAT, as well as which factors contribute to the exercise-induced beiging of WAT are areas of current investigation. Studies investigating the effects of exercise training on BAT mass and function have yielded conflicting data, and hence, is another area of intensive investigation. This review will focus on studies aimed at elucidating the mechanisms regulating exercise training induced-adaptations to adipose tissue. PMID- 27386158 TI - What induces watts in WAT? AB - Excess calories stored in white adipose tissue (WAT) could be reduced either through the activation of brown adipose tissue (BAT) or the development of brown like cells ("beige" or "brite") in WAT, a process named "browning." Calorie dissipation in brown and beige adipocytes might rely on the induction of uncoupling protein 1 (UCP1), which is absent in white fat cells. Any increase in UCP1 is commonly considered as the trademark of energy expenditure. The intracellular events involved in the recruitment process of beige precursors were extensively studied lately, as were the effectors, hormones, cytokines, nutrients and drugs able to modulate the route of browning and theoretically affect fat mass in rodents and in humans. The aim of this review is to update the characterization of the extracellular effectors that induce UCP1 in WAT and potentially provoke calorie dissipation. The potential influence of metabolic cycling in energy expenditure is also questioned. PMID- 27386160 TI - The protein source determines the potential of high protein diets to attenuate obesity development in C57BL/6J mice. AB - The notion that the obesogenic potential of high fat diets in rodents is attenuated when the protein:carbohydrate ratio is increased is largely based on studies using casein or whey as the protein source. We fed C57BL/6J mice high fat high protein diets using casein, soy, cod, beef, chicken or pork as protein sources. Casein stood out as the most efficient in preventing weight gain and accretion of adipose mass. By contrast, mice fed diets based on pork or chicken, and to a lesser extent mice fed cod or beef protein, had increased adipose tissue mass gain relative to casein fed mice. Decreasing the protein:carbohydrate ratio in diets with casein or pork as protein sources led to accentuated fat mass accumulation. Pork fed mice were more obese than casein fed mice, and relative to casein, the pork-based feed induced substantial accumulation of fat in classic interscapular brown adipose tissue accompanied by decreased UCP1 expression. Furthermore, intake of a low fat diet with casein, but not pork, as a protein source reversed diet-induced obesity. Compared to pork, casein seems unique in maintaining the classical brown morphology in interscapular brown adipose tissue with high UCP1 expression. This was accompanied by increased expression of genes involved in a futile cycling of fatty acids. Our results demonstrate that intake of high protein diets based on other protein sources may not have similar effects, and hence, the obesity protective effect of high protein diets is clearly modulated by protein source. PMID- 27386161 TI - Adipose tissue depot specific differences of PLIN protein content in endurance trained rats. AB - Adipose tissue is classified as either white (WAT) or brown (BAT) and differs not only by anatomical location but also in function. WAT is the main source of stored energy and releases fatty acids in times of energy demand, whereas BAT plays a role in regulating non-shivering thermogenesis and oxidizes fatty acids released from the lipid droplet. The PLIN family of proteins has recently emerged as being integral in the regulation of fatty acid storage and release in adipose tissue. Previous work has demonstrated that PLIN protein content varies among adipose tissue depots, however an examination of endurance training-induced depot specific changes in PLIN protein expression has yet to be done. Male Sprague dawley rats (n = 10) underwent 8-weeks of progressive treadmill training (18-25 m/min for 30-60 min at 10% incline) or remained sedentary as control. Following training, under isoflurane induced anesthesia epidydmal (eWAT), inguinal subcutaneous (iWAT) and intrascapular brown adipose tissue (BAT) was excised, and plasma was collected. Endurance training resulted in an increase in BAT PLIN5 and iWAT PLIN3 content, while there was no difference in PLIN protein content in endurance trained eWAT. Interestingly, endurance training resulted in a robust increase in ATGL and CGI-58 in eWAT alone. Together these results suggest the potential of a depot specific function of PLIN3 and PLIN5 in adipose tissue in response to endurance training. PMID- 27386162 TI - Wnt inhibition enhances browning of mouse primary white adipocytes. AB - The global epidemic in obesity and metabolic syndrome requires novel approaches to tackle. White adipose tissue, traditionally seen as a passive energy-storage organ, can be induced to take on certain characteristics of brown fat in a process called browning. The "browned" white adipose tissue, or beige fat, is a potential anti-obesity target. Various signaling pathways can enhance browning. Wnt is a key regulator of adipocyte biology, but its role in browning has not been explored. In this study, we found that in primary mouse adipocytes derived from the inguinal depot, Wnt inhibition by both chemical and genetic methods significantly enhanced browning. The effect of Wnt inhibition on browning most likely targets the beige precursor cells in selected adipose depots. PMID- 27386163 TI - Liver X receptor beta: new player in the regulatory network of thyroid hormone and 'browning' of white fat. AB - The recent discovery of browning of white adipose tissue (WAT) has raised great research interest because of its significant potential in counteracting obesity and type II diabetes. However, the mechanisms underlying browning are still poorly understood. Liver X receptors (LXRs) are one class of nuclear receptors, which play a vital role in regulating cholesterol, triglyceride and glucose metabolism. Following our previous finding that LXRs serve as repressors of UCP1 in classic brown adipose tissue in female mice, we found that LXRs, especially LXRbeta, also repress the browning process of subcutaneous adipose tissue (SAT) in male rodents fed a normal diet. Depletion of LXRs activated thyrotropin releasing hormone positive neurons in the paraventricular area of the hypothalamus, and thus stimulated secretion of thyroid-stimulating hormone from the pituitary. Consequently production of thyroid hormones in the thyroid gland and circulating thyroid hormone level were increased. Moreover, the activity of thyroid signaling in SAT was markedly increased. One unexpected finding of our study is that LXRs are indispensable in the thyroid hormone negative feedback loop at the level of the hypothalamus. LXRs maintain expression of thyroid receptors in the brain and when they are inactivated there is no negative feedback of thyroid hormone in the hypothalamus. Together, our findings have uncovered the basis of increased energy expenditure in male LXR knock-out mice and provided support for targeting LXRs in treatment of obesity. PMID- 27386164 TI - A joint graph inference case study: the C. elegans chemical and electrical connectomes. AB - We investigate joint graph inference for the chemical and electrical connectomes of the Caenorhabditis elegans roundworm. The C. elegans connectomes consist of [Formula: see text] non-isolated neurons with known functional attributes, and there are two types of synaptic connectomes, resulting in a pair of graphs. We formulate our joint graph inference from the perspectives of seeded graph matching and joint vertex classification. Our results suggest that connectomic inference should proceed in the joint space of the two connectomes, which has significant neuroscientific implications. PMID- 27386165 TI - Hitting two birds with one stone: The unforeseen consequences of nested gene knockouts in Caenorhabditis elegans. AB - Nested genes represent an intriguing form of non-random genomic organization in which the boundaries of one gene are fully contained within another, longer host gene. The C. elegans genome contains over 10,000 nested genes, 92% of which are ncRNAs, which occur inside 16% of the protein coding gene complement. Host genes are longer than non-host coding genes, owing to their longer and more numerous introns. Indel alleles are available for nearly all of these host genes that simultaneously alter the nested gene, raising the possibility of nested gene disruption contributing to phenotypes that might be attributed to the host gene. Such dual-knockouts could represent a source of misinterpretation about host gene function. Dual-knockouts might also provide a novel source of synthetic phenotypes that reveal the functional effects of ncRNA genes, whereby the host gene disruption acts as a perturbed genetic background to help unmask ncRNA phenotypes. PMID- 27386166 TI - Interplay between redox and protein homeostasis. AB - The subcellular compartments of eukaryotic cells are characterized by different redox environments. Whereas the cytosol, nucleus and mitochondria are more reducing, the endoplasmic reticulum represents a more oxidizing environment. As the redox level controls the formation of intra- and inter-molecular disulfide bonds, the folding of proteins is tightly linked to its environment. The proteostasis network of each compartment needs to be adapted to the compartmental redox properties. In addition to chaperones, also members of the thioredoxin superfamily can influence the folding of proteins by regulation of cysteine reduction/oxidation. This review will focus on thioredoxin superfamily members and chaperones of C. elegans, which play an important role at the interface between redox and protein homeostasis. Additionally, this review will highlight recent methodological developments on in vivo and in vitro assessment of the redox state and their application to provide insights into the high complexity of redox and proteostasis networks of C. elegans. PMID- 27386167 TI - Cancer cachexia-when proteasomal inhibition is not enough. PMID- 27386169 TI - Espindolol for the treatment and prevention of cachexia in patients with stage III/IV non-small cell lung cancer or colorectal cancer: a randomized, double blind, placebo-controlled, international multicentre phase II study (the ACT-ONE trial). AB - BACKGROUND: Cancer cachexia is a major cause of morbidity and mortality with no widely approved treatment. METHODS: The ACT-ONE trial is a randomized, double blind, parallel group, placebo-controlled, phase II multicentre trial in patients (25-80 years) with stages III or IV colorectal cancer or non-small cell lung cancer-related cachexia that tested two doses of espindolol (a novel non selective beta blocker with central 5-HT1a and partial beta2 receptor agonist effects). The primary endpoint was the difference in the rate of weight change over 16 weeks (linear mixed-effect model for repeated measures) between high-dose espindolol and placebo. RESULTS: Eighty-seven patients were randomized centrally in blocks in a ratio 3:2:1 [42 high dose, 10 mg twice daily (bd):31 placebo:14 low dose, 2.5 mg bd]. High-dose espindolol produced a statistically and clinically significant weight gain (+0.54 kg/4 weeks, 95% CI 0.38-0.70) compared with a weight loss on placebo (-0.21 kg/4 weeks, 95% CI -0.37-0.05); P < 0.0001. High-dose espindolol produced a statistically significant increase in lean body mass, whilst changes in fat mass were neutral. Hand grip strength significantly (high dose -1.15 +/- 0.7 kg, placebo -3.51 +/- 0.8 kg change per 4 weeks; P = 0.0134), stair climbing power, and 6-min walk test non-significantly were all directionally in favour of high-dose espindolol. There were no clinically significant differences in safety signals or survival between treatment groups, although a numerical excess of dyspnoea was seen with high-dose espindolol (19.1%) compared with placebo (3.2%). CONCLUSIONS: This positive trial showed that espindolol 10 mg bd significantly reversed weight loss, improved fat free mass, and maintained fat mass in advanced colorectal cancer and non-small cell lung cancer-related cachexia. This was associated with a significant improvement in handgrip strength, supporting the further investigation of 10 mg bd espindolol for the treatment of cancer cachexia. Although not powered to look at dose response, most treatment effects for low dose lay between high dose and placebo, suggesting that there may be a dose response in the effects of espindolol. PMID- 27386170 TI - Breast carcinoma detection modes and death in a female population in relation to population-based mammography screening. AB - PURPOSE: Associations between population-based screening, breast carcinoma detection modes and breast carcinoma death have not been studied using nationwide data at individual level. We evaluated these in Finland, where invitational age is gradually expanding from 50-59 to 50-69 years in 2008-2017. We also predicted breast carcinoma patterns in 2020 to assess the impact of changing invitational policy on breast carcinoma incidence and mortality. METHODS: The data included breast carcinomas in 2000-2010 (n = 48 040), and deaths due to these carcinomas (n = 4722). We divided carcinomas into those detected before or after the screening age, and those detected at the screening age. The latter was further divided into screen-detected and interval carcinomas, and carcinomas in the non attendees. The prediction of future patterns was based on incidence data from the ten-year period 1998-2007 preceding the period of expanding invitational age in the national programme. RESULTS: Approximately 13% of in situ carcinomas were detected before, 29% after, and 57% at the screening age. In invasive cancers, the percentages were 16%, 42%, and 42%, respectively. At the screening age, more than half of invasive cancers were screening-detected, one quarter interval cancers, and one out of six cancers in the non-attendees. Almost 60% of breast cancer deaths were due to cancers detected after the screening age. By 2020, breast cancers detected at the screening age will increase from 42% to 65%, and breast cancers detected by screening from 23% to 38%. CONCLUSIONS: The study demonstrates a novel approach to examine associations between breast carcinoma incidence and mortality within and outside population-based screening. The results show mammography screening having a distinct role in overall breast carcinoma incidence and mortality. PMID- 27386172 TI - MicroRNA-target interactions in neurodegenerative diseases. PMID- 27386171 TI - Hybrid repair of an aortocaval fistula and inferior vena cava external compression caused by an inflammatory aortoiliac aneurysm: a case study. AB - INTRODUCTION: We report a case of aortocaval fistula successfully treated by hybrid operation. CASE DESCRIPTION: A 73-year-old female suffering from malignant lymphoma and painful leg edema was transferred to our institution. Computed tomography revealed an aortoiliac aneurysm. The inferior vena cava was compressed by displacement of the abdominal aortic aneurysm. The bilateral internal iliac and ovarian veins were markedly dilated. Diagnosis was an aortoiliac aneurysm with aortocaval fistula. The treatment options were open surgery or an intervention with bypass surgery. Because of narrow iliac access for a bifurcated stent graft, aorto-uni stentgraft treatment followed by bypass surgery was finally decided. Following stent graft insertion and iliofemoral artery bypass, the aneurysms and fistula were successfully excluded without endoleaks. To treat the inferior vena cava compression, the kissing technique was used to place bare metallic stents across the bilateral common iliac veins and inferior vena cava, which improved the clinical symptoms. DISCUSSION AND EVALUATION: In this aortocaval fistula caused by AAA, a minimally invasive treatment of stentgraft and bypass surgery with venous flow recovery was chosen as a hybrid treatment. Intravascular intervention was the most suitable in this situation. Bare stent placement for venous occlusion was also effective for revascularization of vena cava flow. CONCLUSION: Recent advances in endovascular devices, including stent grafts and bare metallic stents, will be helpful for effective noninvasive treatment for aortocaval fistula circulation. PMID- 27386173 TI - Purinergic transmission in brain tumors and its impact on drug development. PMID- 27386174 TI - Cannabinoid signalling in glioma cells. PMID- 27386168 TI - Cardiac cachexia: hic et nunc. AB - Cardiac cachexia (CC) is the clinical entity at the end of the chronic natural course of heart failure (HF). Despite the efforts, even the most recent definition of cardiac cachexia has been challenged, more precisely, the addition of new criteria on top of obligatory weight loss. The pathophysiology of CC is complex and multifactorial. A better understanding of pathophysiological pathways in body wasting will contribute to establish potentially novel treatment strategies. The complex biochemical network related with CC and HF pathophysiology underlines that a single biomarker cannot reflect all of the features of the disease. Biomarkers that could pick up the changes in body composition before they convey into clinical manifestations of CC would be of great importance. The development of preventive and therapeutic strategies against cachexia, sarcopenia, and wasting disorders is perceived as an urgent need by healthcare professionals. The treatment of body wasting remains an unresolved challenge to this day. As CC is a multifactorial disorder, it is unlikely that any single agent will be completely effective in treating this condition. Among all investigated therapeutic strategies, aerobic exercise training in HF patients is the most proved to counteract skeletal muscle wasting and is recommended by treatment guidelines for HF. PMID- 27386175 TI - The role of integrins in glioma biology and anti-glioma therapies. PMID- 27386176 TI - Drosophila modelling axonal transport in the face of tau pathology. PMID- 27386177 TI - The oligodendroglia cytoskeleton in health and disease. PMID- 27386178 TI - Tau regulates the localization and function of End Binding proteins in neuronal cells. PMID- 27386179 TI - Multiple signaling pathways of orexin receptors. PMID- 27386180 TI - Galanin receptor ligands. PMID- 27386181 TI - Application of fluorescence methods for characterization of ligand binding to G protein coupled receptors. PMID- 27386182 TI - Reacquisition of cocaine conditioned place preference and its inhibition by previous social interaction: Neurochemical and electrophysiological correlates in the nucleus accumbens corridor. PMID- 27386183 TI - Imaging of alpha2C-adrenoceptors in the living brain: a method to monitor noradrenaline release? PMID- 27386184 TI - The other side of opioid receptor signaling: regulation by protein-protein interaction. PMID- 27386185 TI - Autism as a disease of the synapse: search for mechanistic insight. PMID- 27386186 TI - Elucidating the mechanisms of TDP-43 aggregation in a cellular model of motor neuron disease. PMID- 27386187 TI - The role of dynein mediated transport in the clearance of misfolded proteins responsible for motoneuron diseases. PMID- 27386188 TI - Effects of novel synthetic microneurotrophins in diabetic retinopathy. PMID- 27386189 TI - Unravelling carbon monoxide protection in cerebral ischemia: from the organelle to the organism. PMID- 27386190 TI - The effect of different modes of hypobaric hypoxia on the expression of transcription factor pCREB and pro-survival proteins BDNF and BCL-2 in rat neocortex and hippocampus. PMID- 27386191 TI - Ankrd11 is a chromatin regulator involved in autism that is essential for neural development. PMID- 27386192 TI - Active endocannabinoids are secreted on the surface of microglial microvesicles. PMID- 27386193 TI - Peripheral nerve implants enriched with chemotactic factors for peripheral nervous tissue engineering. PMID- 27386194 TI - Uptake, metabolism and toxicity of iron oxide nanoparticles in cultured microglia, astrocytes and neurons. PMID- 27386195 TI - Regulation of mitochondrial trafficking, function and quality control by the mitochondrial GTPases Miro1 and Miro2. PMID- 27386196 TI - Principles of mitochondrial fusion and fission cycle in neurons. PMID- 27386197 TI - Bioenergetic failure, mitochondrial dysfunction and mitophagy. PMID- 27386198 TI - Activity-dependent neuroprotective protein (ADNP): from autism to Alzheimer's disease. PMID- 27386199 TI - Neuronal-activity regulated gene expression: emphasis on BDNF. PMID- 27386200 TI - Epigenetic mechanisms of hypoxic preconditioning. PMID- 27386201 TI - Altered developmental neuroplasticity due to polysialyltransferase ST8SiaII deficiency in mice leads to schizophrenia-like phenotype. PMID- 27386202 TI - Role of amyloid precursor protein (APP) in regulation of neuronal genes. PMID- 27386203 TI - Anti-inflammatory activities of carbon monoxide-releasing molecules (CO-RMs) in the brain. PMID- 27386204 TI - Carbon monoxide targeting mitochondria in astrocytes: modulation of cell metabolism, redox response and cell death. PMID- 27386205 TI - Transcription Factor Nrf2: a novel target to modulate inflammatory and neuroprotective responses in Parkinson's disease. PMID- 27386206 TI - Neuroprotective effert of carbon monoxide and Nrf2 in cerebral ischemia. PMID- 27386207 TI - The lipogenic regulator Sterol Regulatory Element Binding Factor-1c is required to maintain peripheral nerve structure and function. PMID- 27386208 TI - The molecular control of GnRH neuron development. PMID- 27386209 TI - The role of microvascular endothelial WNT signaling the formation of the blood brain barrier. PMID- 27386210 TI - WNT signaling mechanisms in nociception and sensitization of afferent neurons. PMID- 27386211 TI - WNT signaling in midbrain dopaminergic neuron development and cell replacement therapies for Parkinson's disease. PMID- 27386212 TI - Two steps forward, one step back: successes and failures in structure-based discovery of GPCR ligands. PMID- 27386213 TI - WNT signaling in microglia and the glioma microenvironment. PMID- 27386214 TI - Translational repression in the pathogenesis of FUS- and C9orf72-dependent ALS. PMID- 27386215 TI - Post-transcriptional modifications caused by TDP-43 mutations in mouse and man. PMID- 27386216 TI - Sm-like proteins in the pathogenesis of Spinal Muscular Atrophy. PMID- 27386217 TI - Diverse roles of FUS in Amyotrophic Lateral Sclerosis. PMID- 27386218 TI - The protein quality control system in motoneuron diseases. PMID- 27386219 TI - Neurochemical changes in different brain regions induced by PACAP - relations to neuroprotection. PMID- 27386220 TI - Contribution of the galanin system to inflammation. PMID- 27386221 TI - Characterization of neuropeptides which control cerebellar granule cell survival, migration and differentiation. PMID- 27386222 TI - A new face of orexins action - neuroprotection. PMID- 27386223 TI - Comparison of A1 and A2A receptor dynamics using FRET based receptor sensors. PMID- 27386224 TI - Defining the organizational structure of dopamine and muscarninic acetylcholine receptors. PMID- 27386225 TI - Investigation of GPCR allosterism and dimerization in single living cells using fluorescent ligands. PMID- 27386226 TI - Gliomas and epilepsy: Insights from neuropathological studies in humans. PMID- 27386227 TI - The excitement of conducting research and the practical implications. PMID- 27386228 TI - How to innovate and make successful business. PMID- 27386229 TI - Toxicities of docetaxel: original drug versus generics-a comparative study about 81 cases. AB - INTRODUCTION: Docetaxel is a chemotherapy drug widely prescribed in oncology that recognizes a variety of manufactured generics whose toxicity is increasingly reported. The aim of this study was to compare the toxicities between the original and a generics docetaxel in a Moroccan center. METHODS: In a cross sectional study, we enrolled patients treated with docetaxel from the oncology department of the military hospital of Rabat over a period of 2 years (2013 2014). We compared the prevalence of hypersensitivity reactions, febrile neutropenia, peripheral neuropathy, gastrointestinal, cutaneous, and hematologic toxicities, between four different presentations of docetaxel including the original drug. Only grade II or worse adverse events related to chemotherapy were considered. Treatments discontinuations due to toxicity were also compared. Unusual skin toxicities were included. RESULTS: 81 patients were eligible for analysis [43/generics arm vs. 38/original drug arm. Hematological toxicity was significantly more frequent in the generic arm than in the original drug (32.6 vs. 13.2 %; p = 0.04)]. Also, a signifying higher rate of treatment discontinuation was observed in the generic arm (39.5 vs. 7.9 %, p = 0.001). The use of specific generic increase numerically the skin toxicities (17.6 vs. 0 %, p = 0.026). CONCLUSION: Our data suggest that generics of docetaxel are associated with an increase of hematological and cutaneous toxicities, an increase of treatment discontinuation rate and emphasize the need of a regulation of generics' manufacture. PMID- 27386230 TI - Assessment of selected nutrients and toxic metals in fruits, soils and irrigation waters of Awara Melka and Nura Era farms, Ethiopia. AB - The objective of the present study was to determine the levels of essential nutrients (Na, K, Ca, Mg, Fe, Cu, Zn, Mn) and toxic metals (Pb and Cd) in selected varieties of fruits (banana, grape, guava, mandarin and orange), farmland soils and irrigation waters to assess nutritional impact on health. The freeze dried fruits were digested using HNO3 and HClO4 and the levels of the elements determined using flame atomic absorption spectrometer. The highest amount of K (3480) and Mg (281) and the lowest amount of Na (6.4) and Ca (75) ug/g were obtained in banana compared to other analyzed fruits. Cd was detected in guava (0.2 ug/g), orange (0.3 ug/g) and mandarin (0.1 ug/g), but not detected in banana and grape. Pb was not detected in all the fruits. Appreciable amount of total ascorbic acid was found in guava (1170 ug/g) compared to that of other fruits. Furthermore, farmland soils and irrigation waters were analyzed for the selected metals and physico-chemical properties of soils including pH, electrical conductivity, cation exchange capacity, texture and available phosphorus determined to elucidate factors controlling the availability of metals in fruits. Applying statistical packages, analysis of variances and Pearson correlation, links between metal levels in fruits and those in soil and water samples were evaluated. PMID- 27386231 TI - Hybrid photonic crystal fiber in chemical sensing. AB - BACKGROUND: In this article, a hybrid photonic crystal fiber has been proposed for chemical sensing. A FEM has been applied for numerical investigation of some propagation characteristics of the PCF at a wider wavelength from 0.7 to 1.7 um. The geometrical parameters altered to determine the optimized values. The proposed PCF contains three rings of circular holes in the cladding where the core is formulated with microstructure elliptical holes. RESULTS: The simulation result reveals that our proposed PCF exhibits high sensitivity and low confinement loss for benzene, ethanol and water than the prior PCFs. We have also shown that our proposed PCF shows high birefringence for benzene 1.544 * 10(-3), for ethanol 1.513 * 10(-3) and for water 1.474 * 10(-3) at lambda = 1.33 um. CONCLUSION: The proposed PCF is simple with three rings which can be used for the sensing applications of industrially valuable lower indexed chemicals. PMID- 27386232 TI - Optimal injection rate of ultrasound contrast agent for evaluation of focal liver lesions using an automatic power injector: a pilot study. AB - OBJECTIVE: To determine the optimal bolus injection rate of ultrasound (US) contrast agent in vascular imaging for focal liver lesions. METHODS: Thirteen patients with 13 focal liver lesions (5 hepatocellular carcinomas (HCCs) with cirrhosis, 4 liver metastases, 2 hemangiomas, 1 intrahepatic cholangiocarcinoma, 1 focal nodular hyperplasia) received two bolus injections of Sonazoid (at 0.5 and 2.0 mL/s) using an automatic power injector. The lesion-to-liver contrast ratio at peak enhancement was quantitatively evaluated. Enhancement of the lesions compared to liver parenchyma was assessed by two independent readers using a five-point scale and qualitatively evaluated by receiver operating characteristic (ROC) analysis. RESULTS: For all lesions, the contrast ratio was not significantly different between the two injection rates. For HCCs, the contrast ratio was higher at 0.5 mL/s (7.41 +/- 6.56) than at 2.0 mL/s (4.28 +/- 4.66, p = 0.025). For all lesions, the mean area under the ROC curve (AUC) was not significantly different between the two injection rates. For HCCs, the AUC was greater at 0.5 mL/s than at 2.0 mL/s (AUC: 0.86, p = 0.013). CONCLUSION: In contrast-enhanced US, an injection rate of 0.5 mL/s is superior to an injection rate of 2.0 mL/s for the quantitative and qualitative analysis of HCCs in the cirrhotic liver. PMID- 27386233 TI - Screening regional management options for their impact on climate resilience: an approach and case study in the Venen-Vechtstreek wetlands in the Netherlands. AB - Freshwater systems provide various resources and services. These are often vulnerable to climate change and other pressures. Therefore, enhancing resilience to climate change is important for their long term viability. This paper explores how management options can be evaluated on their resilience implications. The approach included five steps: (1) characterizing the system, (2) characterizing the impacts of climate change and other disturbances, (3) inventorying management options, (4) assessing the impacts of these on climate resilience, and (5) follow up analysis. For the resilience assessment, we used a set of 'resilience principles': homeostasis, omnivory, high flux, flatness, buffering, and redundancy. We applied the approach in a case study in a Dutch wetlands region. Many options in the region's management plan contribute to resilience, however, the plan underutilised several principles, particularly flatness, but also redundancy and omnivory for agriculture, and high flux for nature. Co-benefits was identified as an important additional criterion to obtain support for adaptation from local stakeholders, such as farmers. The approach provided a relatively quick and participatory way to screen options. It allowed us to consider multiple impacts and sectors, multiple dimensions of resilience, and stakeholder perspectives. The results can be used to identify gaps or pitfalls, and set priorities for follow-up analyses. PMID- 27386234 TI - An investigation on NO removal by wet scrubbing using NaClO2 seawater solution. AB - The experiments were conducted to investigate the NO removal by wet scrubbing using NaClO2 seawater solution in a cyclic scrubbing mode. Results show that, when the concentration of NaClO2 in scrubbing solution is higher than 10 mM, a complete removal of NO can be achieved during the cyclic scrubbing process. The breakthrough time for seawater with 15 mM NaClO2 is enhanced by 34.3 % compared with that for NaClO2 freshwater. The extension of the breakthrough time for NaClO2 seawater is mainly ascribed to the improved utilization of NaClO2 in the solution. The good buffering ability of seawater could suppress the acidic decomposition of NaClO2 into ClO2 effectively. The analysis of reaction products indicates that the main anions in the spent liquor are chloride ions and nitrate ions. The calculation of NaClO2 utilization according to the ion chromatography also agrees well with the experimental results of breakthrough times. PMID- 27386235 TI - Large deflection response of restrained steel beams under fire and explosion loads. AB - A numerical study on the response of steel beams to fire and explosion is presented in this paper. First, a unified computing model, which can be used to simulate the behaviour of beams under four loading scenarios that involve fire and explosion or impact, is constructed. The proposed technique allows complete transparency of the influence of the various parameters on the structural behaviour. Second, the effects of load level on critical temperature are analyzed for various static and explosion load ratios. Two cases of explosion and fire loading sequences are compared, it is shown that the critical temperature of the beam subjected to fire followed by an explosion is lower than that of the beam subjected to an explosion followed by fire. The influence of temperature on the p i diagram is investigated, an iso-damage surface is introduced to distinguish safe and unsafe regions. Third, the limiting temperature criteria are further examined. That is, the first and second limiting temperatures can be determined when the dimensional catenary force is equal to zero or to one, which corresponds to the bending or stretching plastic hinge, respectively. PMID- 27386236 TI - Fungal infection and aflatoxin contamination in maize collected from Gedeo zone, Ethiopia. AB - Aflatoxins contamination of maize exhibits a serious threat to human and animal health over the past few decades. To protect the safety of food commodities, regular monitoring for afltoxins in food is necessary. In the proposed study, we have followed a rapid and sensitive biosensor approach as well as thin layer chromatography method for quantification of aflatoxins. Our data demonstrate that all the samples tested were beyond the safety level of aflatoxins as determined by Food and Drug Administration and European Union. Results of fungal mycoflora evidenced the massive presence of Aspergillus species (75 %) followed by Fusarium (11 %), Penicillium (8 %) and Trichoderma (6 %) as characterized by biochemical and sporulation properties. Use of internationally developed biosensor for detection of fungal toxin in this work is the first approach that was utilized in the developing country like Ethiopia. In the end, we conclude that fungal contaminant and there metabolites are potential threat to the agricultural industry and require urgent intervention. PMID- 27386237 TI - Experimental determination of TRIP-parameter K for mild- and high-strength low alloy steels and a super martensitic filler material. AB - A combined experimental numerical approach is applied to determine the transformation induced plasticity (TRIP)-parameter K for different strength low alloy steels of grade S355J2+N and S960QL as well as the super martensitic filler CN13-4-IG containing 13 wt% chromium and 4 wt% nickel. The thermo-physical analyses were conducted using a Gleeble ((r)) 3500 facility. The thermal histories of the specimens to be tested were extracted from corresponding simulations of a real gas metal arc weldment. In contrast to common TRIP experiments which are based on complex specimens a simple flat specimen was utilized together with an engineering evaluation method. The evaluation method was validated with literature values for the TRIP-parameter. It could be shown that the proposed approach enables a correct description of the TRIP behavior. PMID- 27386238 TI - Numerical investigation of soil plugging effect inside sleeve of cast-in-place piles driven by vibratory hammers in clays. AB - During driving sleeve of cast-in-place piles by vibratory hammers, soils were squeezed into sleeve and then soil plugging was formed. The physic-mechanical properties of the soil plug have direct influence on the load transmission between the sleeve wall and soil plug. Nevertheless, the researches on this issue are insufficient. In this study, finite element and infinite element coupling model was introduced, through the commercial code ABAQUS, to simulate the full penetration process of the sleeve driven from the ground surface to the desired depth by applying vibratory hammers. The research results indicated that the cyclic shearing action decreases both in soil shear strength and in granular cementation force when the sleeve is driven by vibratory hammers, which leads to a partially plugged mode of the soil plug inside the sleeve. Accordingly, the penetration resistance of sleeve driven by vibratory hammers is the smallest compared to those by other installation methods. When driving the sleeve, the annular soil arches forming in the soil plug at sleeve end induce a significant rise in the internal shaft resistance. Moreover, the influence of vibration frequencies, sleeve diameters, and soil layer properties on the soil plug was investigated in detail, and at the same time improved formulas were brought forward to describe the soil plug resistance inside vibratory driven sleeve. PMID- 27386239 TI - Risk factors and influence of carbapenem exposure on the development of carbapenem resistant Pseudomonas aeruginosa bloodstream infections and infections at sterile sites. AB - BACKGROUND: Patients with Pseudomonas aeruginosa infections from blood or sterile sites were evaluated to determine risk factors associated with carbapenem resistance (CRPA) compared to carbapenem sensitivity (CSPA) as well as prior carbapenem use and the development of resistance. FINDINGS: Retrospective chart review of 80 patients hospitalized with a documented P. aeruginosa infection during 2010-2011. Stored isolates were retested with both Kirby-Bauer disk diffusion and E-tests. Clinical characteristic of patients in the CRPA (N = 21) and the CSPA (N = 59) groups were similar. Hospital acquired (HA) infections were more common in the CRPA group compared to the CSPA group (71 vs 44 %, p = 0.04) and CRPA patients were more likely to have a Foley catheter at the time of infection (71 vs 37 %, p = 0.01). There was more carbapenem use in the CRPA group prior to onset of infection (59 vs 22 %, OR 5.1, 95 % CI 1.3-20.8, p = 0.01). Length of stay was significantly longer in the CRPA group (mean 44 days) compared to the CSPA group (mean 23 days), p = 0.02. Mortality between the two groups was similar and there were no differences between groups for death attributable to Pseudomonas. CONCLUSIONS: Patients with CRPA were more likely to have HA infections and to have a multidrug resistant profile. Other identifiable risks included a Foley catheter in place at the time of infection and exposure to a carbapenem prior to infection. Prompt removal of devices and judicious use of antibiotics may be interventions that can impact the development of this kind of infections. PMID- 27386240 TI - Fast entropy-based CABAC rate estimation for mode decision in HEVC. AB - High efficiency video coding (HEVC) seeks the best code tree configuration, the best prediction unit division and the prediction mode, by evaluating the rate distortion functional in a recursive way and using a "try all and select the best" strategy. Further, HEVC only supports context adaptive binary arithmetic coding (CABAC), which has the disadvantage of being highly sequential and having strong data dependencies, as the entropy coder. So, the development of a fast rate estimation algorithm for CABAC-based coding has a great practical significance for mode decision in HEVC. There are three elementary steps in CABAC encoding process: binarization, context modeling, and binary arithmetic coding. Typical approaches to fast CABAC rate estimation simplify or eliminate the last two steps, but leave the binarization step unchanged. To maximize the reduction of computational complexity, we propose a fast entropy-based CABAC rate estimator in this paper. It eliminates not only the modeling and the coding steps, but also the binarization step. Experimental results demonstrate that the proposed estimator is able to reduce the computational complexity of the mode decision in HEVC by 9-23 % with negligible PSNR loss and BD-rate increment, and therefore exhibits applicability to practical HEVC encoder implementation. PMID- 27386242 TI - mCAF: a multi-dimensional clustering algorithm for friends of social network services. AB - In recent years, social network services have grown rapidly. The number of friends of each user using social network services has also increased significantly and is so large that clustering and managing these friends has become difficult. In this paper, we propose an algorithm called mCAF that automatically clusters friends. Additionally, we propose methods that define the distance between different friends based on different sets of measurements. Our proposed mCAF algorithm attempts to reduce the effort and time required for users to manage their friends in social network services. The proposed algorithm could be more flexible and convenient by implementing different privacy settings for different groups of friends. According to our experimental results, we find that the improved ratios between mCAF and SCAN are 35.8 % in similarity and 84.9 % in F 1 score. PMID- 27386241 TI - Failure patterns and survival outcomes in triple negative breast cancer (TNBC): a 15 year comparison of 448 non-Hispanic black and white women. AB - PURPOSE: Triple negative breast cancer (TNBC) is a distinct subtype of breast cancer with unique pathologic, molecular and clinical behavior. It occurs more frequently in young blacks and has been reported to have a shorter disease-free interval. We undertook this study to analyze the demographic characteristics, failure patterns, and survival outcomes in this disease. METHODS: A total of 448 non-Hispanic black and white women were identified over a 15 year period from 1996 to 2011. Demographic and clinical information including age, race, menopausal status, stage, tumor characteristics, and treatments were collected. Fisher's exact test and multivariable Cox regression were used to compare failure patterns and survival outcomes between races. RESULTS: 49 % (n = 223) were black. 59 % patients were between 41 and 60 years, with 18 % <=40 years. 57 % were premenopausal and 89 % had grade 3 tumors. Stage II (47 %) was most frequent stage at diagnosis followed by stage III (28 %). 32 % had lymphovascular invasion. Adjusting for age, stage, and grade, there was no difference in survival outcomes (OS, DFS, LFFS, and DFFS) between the two races. 62 (14 %) patients failed locally either in ipsilateral breast or chest wall, and 19 (4 %) failed in the regional lymphatics. Lung (18 %) was the most frequent distant failure site with <12 % each failing in brain, liver and bones. CONCLUSION: Failure patterns and survival outcomes did not differ by race in this large collection of TNBC cases. Lung was the predominate site of distant failure followed by brain, bone, and liver. Few patients failed in the regional lymphatics. PMID- 27386243 TI - Study of streptomycin-induced ototoxicity: protocol for a longitudinal study. AB - Hearing impairment is due to various causes including ototoxicity from aminoglycosides. The susceptibility to aminoglycosides increases in the presence of certain mitochondria gene mutations. There is unrestrained use of aminoglycosides in many developing nations which may worsen the burden of hearing impairment in these countries but there is lack of data to drive required policy changes. Streptomycin (an aminoglycoside) is part of the drug regimen in re treatment of tuberculosis. Exploring the impact of streptomycin ototoxicity in tuberculosis patients provides a unique opportunity to study aminoglycoside ototoxicity within the population thus providing data that can inform policy. Also, since streptomycin ototoxicity could adversely affect treatment adherence in tuberculosis patients this study could enable better pre-treatment counseling with subsequent better treatment adherence. Patients on tuberculosis re-treatment will be recruited longitudinally from Direct Observation Therapy-Short course centers. A baseline full audiologic assessment will be done before commencement of treatment and after completion of treatment. Early detection of ototoxicity will be determined using the American Speech and Hearing Association criteria and genetic analysis to determine relevant mitochondria gene mutations will be done. The incidence of ototoxicity in the cohort will be analyzed. Both Kaplan-Meier survival curve and Cox proportional hazards tests will be utilized to determine factors associated with development of ototoxicity and to examine association between genotype status and ototoxicity. This study will provide data on the burden and associated predictors of developing aminoglycoside induced ototoxicity. This will inform public health strategies to regulate aminoglycoside usage and optimization of treatment adherence and the management of drug-induced ototoxicity among TB patients. Furthermore the study will describe mitochondrial gene mutations associated with ototoxicity in the African population. PMID- 27386244 TI - Effect of water stress on growth of three linseed (Linum usitatissimum L.) varieties. AB - Linseed (Linum usitatissimum L.) is an annual oil crop that accounts for approximately 1 % of the world's oilseed supplies. It produces seeds that are rich in the health-promoting omega-3 fatty acid, alpha-linolenic. In Kenya, linseed is grown in the Rift Valley and Western regions, places which often experience drought. This study was aimed at evaluating the effect of water stress on growth of three linseed cultivars and to establish the extent of drought tolerance in the three cultivars. A greenhouse pot experiment in a completely randomized design was conducted at Jomo Kenyatta University of Agriculture and Technology, Kenya. The pots were well watered until the fourth week when watering was completely withheld to a half of the pots (stressed) while the other half (well watered control) was maintained at 90 % field capacity. Destructive harvesting was done when the stressed pots were at 90, 70, 60, 50, 40 % field capacities and at permanent wilting point. The experiment was replicated thrice and was repeated twice (February-May and August-November 2014). There were no significant differences in production of leaves, plant height, number of tillers and biomass between the three varieties in both seasons. Subjecting the linseed varieties to permanent wilting resulted in reduced production of leaves, growth in height, production of tillers and dry weight by 20-40 %. Decline in all growth parameters begun when 30-80 % of available soil water had been used up. There existed linear relationships between the various evaluated growth parameters. These relationships were not influenced either by the water status of soil or the varieties. Relative water content for the three linseed varieties declined after 25-67 % of available soil water had been used up. PMID- 27386245 TI - Influence of preactivation on fascicle behavior during eccentric contraction. AB - BACKGROUND: Because muscle fascicle behavior affects to the force-generating capability, understanding of muscle fascicle length changes during dynamic movements is important. Preactivation may affect the muscle fascicle length changes, especially in the case of eccentric contraction. However, its influence has not been clarified. To this end, muscle fascicle behavior during eccentric contraction was compared between preactivation and no-preactivation conditions. RESULTS: Seven healthy men (24.6 +/- 2.2 years, 169 +/- 2 cm, 68.0 +/- 5.1 kg) participated in this study. An eccentric knee extension controlled by a Biodex system was adopted as the testing motion. Muscle fascicle behavior of vastus lateralis during eccentric knee extensions was compared following two conditions. In preactivation condition, isometric preactivation was conducted before initiating eccentric contraction. On the other hand, in no-preactivation condition, muscle contraction was initiated immediately after initiating the knee angle change induced by a dynamometer. The muscle fascicle length at the onset of eccentric contraction was significantly shorter in preactivation condition than in no-preactivation condition (Cohen's d = 0.98, p < 0.001) although that at the end of eccentric contraction was not different (Cohen's d = 0.08, p = 0.844). The muscle fascicle was elongated throughout the eccentric contraction phase in preactivation condition. On the other hand, muscle fascicle was shortened in the first part, and then elongated in the latter part of the eccentric contraction phase in no-preactivation condition. CONCLUSIONS: The muscle fascicle is shortened even during eccentric contraction phase. However, this shortening is disappeared when preactivation is conducted. PMID- 27386246 TI - Porphyromonas gingivalis-induced miR-132 regulates TNFalpha expression in THP-1 derived macrophages. AB - BACKGROUND: Periodontitis is a chronic inflammatory disease induced by periodontopathogens such as Porphyromonas gingivalis (P. gingivalis). MicroRNAs (miRNAs) are small single-stranded noncoding RNAs that regulate gene expression at the level of translation. MiRNAs have been reported to be involved in inflammatory processes. In this study, we examined the effects of P. gingivalis induced inflammatory miRNAs expression on TNFalpha production in THP-1 derived macrophages. RESULTS: Porphyromonas gingivalis induced the expression of miR-132. P. gingivalis-induced miR-132 expression was significantly inhibited by TLR2/4 knock-down and NF-kappaB inhibitor. Additionally, miR-132 antagomir strongly repressed production of TNFalpha. The expression of NFE2L2 and NFAT5, the putative target genes of miR-132 involved in regulation of TNFalpha, decreased in response to P. gingivalis. Furthermore, miR-132 antagomir rescued P. gingivalis induced suppression of NFE2L2 and NFAT5. CONCLUSIONS: These results suggest that the induction of miR-132 by P. gingivalis can modulate the pathogenesis of periodontitis induced via regulatory expression of TNFalpha. PMID- 27386247 TI - Studies on the alterations in haematological indices, micronuclei induction and pathological marker enzyme activities in Channa punctatus (spotted snakehead) perciformes, channidae exposed to thermal power plant effluent. AB - The present study was conducted to assess the toxicity of thermal power plant effluent containing heavy metals (Fe > Cu > Zn > Mn > Ni > Co > Cr) on haematological indices, micronuclei, lobed nuclei and activity of pathological marker enzymes [alkaline phosphatase (ALP), aspartate transferase (AST), alanine transferase (ALT) and creatine kinase (CK)] in Channa punctatus. Total erythrocyte count (-54.52 %), hemoglobin (-36.98 %), packed cell volume (-36.25 %), mean corpuscular hemoglobin concentration (-1.41 %) and oxygen (O2) carrying capacity (-37.04 %) declined significantly over reference fish, however total leukocyte count (+25.43 %), mean corpuscular hemoglobin (+33.52 %) and mean corpuscular volume (+35.49 %) showed elevation. High frequency of micronuclei (1133.3 %) and lobed nuclei (150 %) were observed in exposed fish which may indicate mutagenesis. Activities of pathological marker enzymes ALP, AST, ALT and CK increased significantly in serum of exposed fish. The ratio of ALT: AST in exposed fish was beyond 1 which indicates manifestation of pathological processes. These biomarkers show that fish have macrocytic hypochromic anemia. Leukocytosis showed general defence response against heavy metal toxicity and marker enzymes showed tissue degeneration. In conclusion, thermal power plant effluent has strong potential to induce micronuclei, tissue pathology, making the fish anemic, weak, stressed and vulnerable to diseases. PMID- 27386248 TI - Biodegradation of different formulations of polyhydroxybutyrate films in soil. AB - BACKGROUND: Petroleum polymers contribute to non-degradable waste materials and it would therefore be desirable to produce ecofriendly degradable materials. Biodegradation of polyhydroxybutyrate (PHB) in the presence of oligomer hydrolase and PHB depolymerase gave 3-hydroxybutyric acid which could be oxidized to acetyl acetate. Several bacteria and fungi can degrade PHB in the soil. RESULTS: Biodegradation of PHB showed a significant decrease in the molecular weight (Mw), number-average molecular weight (Mn) and the dispersity (Mw/Mn) for all the film formulations. Nanofibers of PHB and its composites showed faster degradation compared to other films and displayed complete degradation after 3 weeks. The SEM micrographs showed various surface morphology changes including alterations in appearance of pores, cavity, grooves, incisions, slots and pointers. Such changes were due to the growth of microorganisms that secreted PHB depolymerase enzyme which lead to the biopolymer films degradation. However, PHB nanofibers and its composites films in the presence of TiO2 demonstrated more surface changes with rupture of most nanofibers in which there was a drop in fibres diameter. CONCLUSIONS: The degradation of biopolymers help to overcome some of the pollution problems associated with the use of petroleum polymers. PHB nanofiber and its TiO2 composite were degraded faster compared to other PHB film types due to their three dimensional and high surface area structures. The presence of TiO2 nanoparticles in the composite films slowdown the degradation process compared to PHB films. Additionally, the PHB and its composite films that were prepared from UV treated PHB films led to acceleration of the degradation.Graphical abstractBiodegradation of polyhydroxybutyrate films in soil. PMID- 27386249 TI - Preclinical study of diagnostic performances of contrast-enhanced spectral mammography versus MRI for breast diseases in China. AB - PURPOSE: To evaluate diagnostic performances of CESM for breast diseases with comparison to breast MRI in China. MATERIALS AND METHODS: Sixty-eight patients with 77 breast lesions underwent MR and CESM. Two radiologists interpreted either MRI or CESM images, separately and independently. BI-RADS 1-3 and BI-RADS 4-5 were classified into the suspicious benign and suspicious malignant groups. Diagnostic accuracy parameters were calculated. Receiver operating characteristic (ROC) curves were constructed for the two modalities. The agreement and correlation between maximum lesion diameter based on CESM and MRI, or CESM and pathology were analyzed. RESULTS: Diagnostic accuracy parameters for CESM were sensitivity 95.8 %, specificity 65.5 %, PPV 82.1 %, NPV 90.5 % and accuracy 84.4 %. The diagnostic accuracy parameters for breast MRI were sensitivity 93.8 %, specificity 82.8 %, PPV 88.2 %, NPV 92.3 %and accuracy 89.6 %. Area under the curve (AUC) of ROC was 0.96 for breast MRI and 0.88 for CESM. The Bland-Altman plots showed a mean difference of 0.7 mm with 95 % limits of agreement of 11.4 mm in tumor diameter measured using CESM and breast MRI. The differences of size measurement between CESM and breast MRI were significant, whereas no difference was observed between CESM and pathology as well as between breast MRI and pathology. The better correlation with pathological results was found in CESM than breast MRI. CONCLUSION: Our study demonstrates that CESM possesses better diagnostic performances than breast MRI in terms of diagnostic sensitivity and lesion size assessment. And CESM is a good alternative method of screening breast cancer in high-risk people. PMID- 27386250 TI - Effects of permissive hypercapnia on pulmonary and neurodevelopmental sequelae in extremely low birth weight infants: a meta-analysis. AB - OBJECTIVES: To perform a systematic review and meta-analysis of the efficacy and safety of permissive hypercapnia in extremely low birth weight infants. METHODS: A systematic search of MEDLINE, EMBASE, the Cochrane Database of randomized trials. Eligibility and quality of trials were assessed, and data on study design, patient characteristics, and relevant outcomes were extracted. RESULTS: Four studies that enrolled a total of 693 participants were selected. Meta analysis revealed no effect of permissive hypercapnia on decreasing rates of bronchopulmonary dysplasia (BPD). Permissive hypercapnia also had no significant effect on mortality, intraventricular haemorrhage (IVH), IVH (grade 3-4), periventricular leukomalacia (PVL), necrotising enterocolitis (NEC), retinopathy of prematurity (ROP) or air leaks in extremely low birth weight infants. Neurodevelopmental outcomes were comparable at 18-22 months' corrected age in two studies. permissive hypercapnia did not increase the risk of cerebral palsy, Mental Developmental Index <70, Psychomotor Developmental Index <70, visual deficit, or hearing deficit. CONCLUSIONS: Permissive hypercapnia did not reduce the rate of BPD in extremely low birth weight infants. The rates of mortality, IVH, PVL, NEC, ROP and neurodevelopmental outcomes did not differ between these two groups. These results suggest that permissive hypercapnia does not bring extra benefits in extremely low birth weight infants. PMID- 27386251 TI - Automated vision system for fabric defect inspection using Gabor filters and PCNN. AB - In this study, an embedded machine vision system using Gabor filters and Pulse Coupled Neural Network (PCNN) is developed to identify defects of warp-knitted fabrics automatically. The system consists of smart cameras and a Human Machine Interface (HMI) controller. A hybrid detection algorithm combing Gabor filters and PCNN is running on the SOC processor of the smart camera. First, Gabor filters are employed to enhance the contrast of images captured by a CMOS sensor. Second, defect areas are segmented by PCNN with adaptive parameter setting. Third, smart cameras will notice the controller to stop the warp-knitting machine once defects are found out. Experimental results demonstrate that the hybrid method is superior to Gabor and wavelet methods on detection accuracy. Actual operations in a textile factory verify the effectiveness of the inspection system. PMID- 27386252 TI - On implementation of DCTCP on three-tier and fat-tree data center network topologies. AB - A data center is a facility for housing computational and storage systems interconnected through a communication network called data center network (DCN). Due to a tremendous growth in the computational power, storage capacity and the number of inter-connected servers, the DCN faces challenges concerning efficiency, reliability and scalability. Although transmission control protocol (TCP) is a time-tested transport protocol in the Internet, DCN challenges such as inadequate buffer space in switches and bandwidth limitations have prompted the researchers to propose techniques to improve TCP performance or design new transport protocols for DCN. Data center TCP (DCTCP) emerge as one of the most promising solutions in this domain which employs the explicit congestion notification feature of TCP to enhance the TCP congestion control algorithm. While DCTCP has been analyzed for two-tier tree-based DCN topology for traffic between servers in the same rack which is common in cloud applications, it remains oblivious to the traffic patterns common in university and private enterprise networks which traverse the complete network interconnect spanning upper tier layers. We also recognize that DCTCP performance cannot remain unaffected by the underlying DCN architecture hence there is a need to test and compare DCTCP performance when implemented over diverse DCN architectures. Some of the most notable DCN architectures are the legacy three-tier, fat-tree, BCube, DCell, VL2, and CamCube. In this research, we simulate the two switch-centric DCN architectures; the widely deployed legacy three-tier architecture and the promising fat-tree architecture using network simulator and analyze the performance of DCTCP in terms of throughput and delay for realistic traffic patterns. We also examine how DCTCP prevents incast and outcast congestion when realistic DCN traffic patterns are employed in above mentioned topologies. Our results show that the underlying DCN architecture significantly impacts DCTCP performance. We find that DCTCP gives optimal performance in fat-tree topology and is most suitable for large networks. PMID- 27386254 TI - Keys to active ageing: new communication technologies and lifelong learning. AB - The purpose of this study is to describe the creation and implementation of an ICT education program for the elderly in various Active Participation Centers in Almeria (Spain), assessing its impact on quality of life. From a randomized sample of 200 individuals over the age of 55. Results reveal a high degree of participant satisfaction (76.6 %), as well as improvements in quality of life as compared to the control group after the 3 month program health factor: p = 0.004; leisure and activity factor: p = 0.001; Satisfaction with Life Factor: p < 0.001. The analysis conducted to determine the influence of age and gender on quality of life indicates that there are statistically significant differences in regards to age (the younger groups had higher scores) and gender (the males). This study may serve to facilitate similar works that promotes on-going education in different locations and across the lifespan. PMID- 27386253 TI - Association of HOMER1 rs2290639 with suicide attempts in Hong Kong Chinese and the potentially functional role of this polymorphism. AB - OBJECTIVE: Animal evidence and genetic studies suggest that HOMER1 (homer homolog 1) is involved in the etiology of suicidal behavior and major depression disorder (MDD). However, most of genetic studies were performed in Caucasians and the potentially functional role of associated polymorphisms in HOMER1 was seldom reported. The purpose of this study was to investigate the association of a HOMER1 polymorphism rs2290639 with suicide attempts (SA) and MDD in Hong Kong Chinese, and then briefly elucidate the potentially functional role of the associated polymorphism. METHODS: NEO personality inventory, impulsiveness and depression rating scales were completed by the subjects. The association studies of HOMER1 rs2290639 with SA or MDD were performed by case-control association studies. The bioinformatics analyses were adapted to predict potential transcription factors binding sites for the associated polymorphism. RESULTS: The association studies and meta-analysis suggested that the HOMER1 rs2290639 was significantly associated with susceptibility to SA but seemed not to be associated with MDD in Hong Kong Chinese. This polymorphism might affect the transcription of the HOMER1 gene through interacting with a reliable transcription factor as found by three of four bioinformatics tools. In addition, close correlations between impulsiveness and NEO personality five factors were found in SA and MDD patients, which provide a possible way to assess the impulsiveness of patients through subjects' personality profiles for Hong Kong Chinese. CONCLUSIONS: The HOMER1 rs2290639 polymorphism was significantly associated with susceptibility to SA in Hong Kong Chinese affected by psychiatric disorders, which might be explained by the potentially functional role of this polymorphism. PMID- 27386255 TI - GFP as a marker for transient gene transfer and expression in Mycoplasma hyorhinis. AB - Mycoplasma hyorhinis (M. hyorhinis) is an opportunistic pathogen of pigs and has been shown to transform cell cultures, which has increased the interest of researchers. The green florescence proteins (GFP) gene of Aquorea victoria, proved to be a vital marker to identify transformed cells in mixed populations. Use of GFP to observe gene transfer and expression in M. hyorhinis (strain HUB-1) has not been described. We have constructed a pMD18-O/MHRgfp plasmid containing the p97 gene promoter, origin of replication, tetracycline resistance marker and GFP gene controlled by the p97 gene promoter. The plasmid transformed into M. hyorhinis with a frequency of ~4 * 10(-3) cfu/ug plasmid DNA and could be detected by PCR amplification of the GFP gene from the total DNA of the transformant mycoplasmas. Analysis of a single clone grown on KM2-Agar containing tetracycline, showed a green fluorescence color. Conclusively, this report suggests the usefulness of GFP to monitor transient gene transfer and expression in M. hyorhinis, eventually minimizing screening procedures for gene transfer and expression. PMID- 27386256 TI - Efficient reference-free adaptive artifact cancellers for impedance cardiography based remote health care monitoring systems. AB - In this paper, a new model for adaptive artifact cancelation in impedance cardiography (ICG) signals is presented. It is a hybrid model based on wavelet decomposition and an adaptive filter. A novel feature of this model is the implementation of reference-free adaptive artifact cancellers (AAC). For this implementation, the reference signal is constructed using a wavelet transformation. During critical conditions the filter weights may be negative and cause an imbalance in the convergence. To overcome this problem, we introduce non negative adaptive algorithms in the proposed artifact canceller. To accelerate the performance of the AAC, we propose exponential non-negative and normalized non-negative algorithms to update the filter coefficients. The computational complexity of the filtering section in a remote health care system is important to avoid inter-symbol interference of the incoming samples. This can be achieved by combining sign-based algorithms with the adaptive filtering section. Finally, several AACs are developed using variants of the non-negative algorithms and performance measures are computed and compared. All of the proposed AACs are tested on actual ICG signals. Among the AACs evaluated, sign regressor normalized non-negative LMS (SRN(3)LMS) based adaptive artifact canceller achieves highest signal to noise ratio (SNR). The SNR achieved by this algorithm in baseline wander artifact elimination is 8.5312 dBs, in electrode muscle artifact elimination is 7.5908 dBs and in impedance measurement artifact elimination is 8.4231 dBs. PMID- 27386257 TI - Conceptual design of a high-speed electromagnetic switch for a modified flux coupling-type SFCL and its application in renewable energy system. AB - The modified flux-coupling-type superconducting fault current (SFCL) is a high efficient electrical auxiliary device, whose basic function is to suppress the short-circuit current by controlling the magnetic path through a high-speed switch. In this paper, the high-speed switch is based on electromagnetic repulsion mechanism, and its conceptual design is carried out to promote the application of the modified SFCL. Regarding that the switch which is consisting of a mobile copper disc, two fixed opening and closing coils, the computational method for the electromagnetic force is discussed, and also the dynamic mathematical model including circuit equation, magnetic field equation as well as mechanical motion equation is theoretically deduced. According to the mathematical modeling and calculation of characteristic parameters, a feasible design scheme is presented, and the high-speed switch's response time can be less than 0.5 ms. For that the modified SFCL is equipped with this high-speed switch, the SFCL's application in a 10 kV micro-grid system with multiple renewable energy sources are assessed in the MATLAB software. The simulations are well able to affirm the SFCL's performance behaviors. PMID- 27386258 TI - An Information System for European culture collections: the way forward. AB - Culture collections contain indispensable information about the microorganisms preserved in their repositories, such as taxonomical descriptions, origins, physiological and biochemical characteristics, bibliographic references, etc. However, information currently accessible in databases rarely adheres to common standard protocols. The resultant heterogeneity between culture collections, in terms of both content and format, notably hampers microorganism-based research and development (R&D). The optimized exploitation of these resources thus requires standardized, and simplified, access to the associated information. To this end, and in the interest of supporting R&D in the fields of agriculture, health and biotechnology, a pan-European distributed research infrastructure, MIRRI, including over 40 public culture collections and research institutes from 19 European countries, was established. A prime objective of MIRRI is to unite and provide universal access to the fragmented, and untapped, resources, information and expertise available in European public collections of microorganisms; a key component of which is to develop a dynamic Information System. For the first time, both culture collection curators as well as their users have been consulted and their feedback, concerning the needs and requirements for collection databases and data accessibility, utilised. Users primarily noted that databases were not interoperable, thus rendering a global search of multiple databases impossible. Unreliable or out-of-date and, in particular, non-homogenous, taxonomic information was also considered to be a major obstacle to searching microbial data efficiently. Moreover, complex searches are rarely possible in online databases thus limiting the extent of search queries. Curators also consider that overall harmonization-including Standard Operating Procedures, data structure, and software tools-is necessary to facilitate their work and to make high-quality data easily accessible to their users. Clearly, the needs of culture collection curators coincide with those of users on the crucial point of database interoperability. In this regard, and in order to design an appropriate Information System, important aspects on which the culture collection community should focus include: the interoperability of data sets with the ontologies to be used; setting best practice in data management, and the definition of an appropriate data standard. PMID- 27386259 TI - Hypothetical granulin-like molecule from Fasciola hepatica identified by bioinformatics analysis. AB - Fasciola hepatica is considered an emergent human pathogen, causing liver fibrosis or cirrhosis, conditions that are known to be direct causes of cancer. Some parasites have been categorized by WHO as carcinogenic agents such as Opisthorchis viverrini, a relative of F. hepatica. Although these two parasites are from the same class (Trematoda), the role of F. hepatica in carcinogenesis is unclear. We hypothesized that F. hepatica might share some features with O. viverrini and to be responsible to induce proliferation of host cells. We analyzed the recently released genome of F. hepatica looking for a gene coding a granulin-like growth factor, a protein secreted by O. viverrini (Ov-GRN-1), which is a potent stimulator of proliferation of host cells. Using computational biology tools, we identified a granulin-like molecule in F. hepatica, here termed FhGLM, which has high sequence identity level to Ov-GRN-1 and human progranulin. We found evidence of an upstream promoter compatible with the expression of FhGLM. The FhGLM architecture showed to have five granulin domains, one of them, the domain 3, was homologue to Ov-GRN-1 and human GRNC. The structure of the FhGLM granulin domain 3 resulted to have the overall folding of its homologue the human GRNC. Our findings show the presence of a homologue of a potent modulator of cell growth in F. hepatica that might have, as other granulins, a proliferative action on host cells during fascioliasis. Future experimental assays to demonstrate the presence of FhGLM in F. hepatica are needed to confirm our hypothesis. PMID- 27386260 TI - Saudi adults satisfaction with community pharmacy services. AB - BACKGROUND: Community pharmacists play a significant role in patient health care in Saudi Arabia and are directly responsible for medication-related counseling. Aim To assess Saudi Adults satisfaction with community pharmacy services and the secondary objective is obtaining an insight of their needs in patient counseling service. METHODS: This cross-sectional survey was conducted via a questionnaire distributed to a representative sample of 650 Saudi adults approached at pharmacists and public places in areas of Riyadh during March 2014. RESULTS: 500 Complete questionnaires were collected, and the response rate was 77 %. Around 41 % were satisfied with Saudi pharmacy services. Out of these, 57 % attributed their satisfaction to pharmacist counseling on current medication, 96 % to appropriate dosage regimen explanation and 73 % to appropriate time spent in counseling (p < 0.001). When asked about reasons for dissatisfaction, 82 % of the unsatisfied group stated that pharmacists fail to ask about comorbid diseases and 78 % reported unavailability of dedicated pharmacist for patient counseling (p < 0.001). CONCLUSION: Saudi adults have variable levels of satisfaction with community pharmacy services. To increase levels of satisfaction, it is necessary to provide adequate pharmacist training in community pharmacies. PMID- 27386261 TI - A comparative study of the photosynthetic capacity in two green tide macroalgae using chlorophyll fluorescence. AB - Green tides have occurred in the Yellow Sea, China, every year from 2007 to 2015. The free-floating Ulva prolifera (Muller) J. Agardh was the causative macroalgal species. The co-occurring, attached U. intestinalis was also observed. Photosynthetic capacities were determined using chlorophyll fluorescence in situ and after 7 days lab acclimation, and a significant differences were noted. Pigment composition showed no obvious differences, but concentrations varied significantly, especially chlorophyll b in U. prolifera two times increase was observed after acclimation. The optimal photochemical efficiency of PS II (Fv/Fm) was significantly higher in U. prolifera. Photosynthetic rate (alpha), maximum relative electron transport rate (rETRmax), and minimum saturating irradiance (Ek), obtained from rapid light response curves (RLCs), showed almost the same photosynthetic physiological status as Fv/Fm. Quenching coefficients and low temperature (77 K) chlorophyll fluorescence emission spectra of thylakoid membranes analysis showed U. prolifera has a better recovery activity and plasticity of PSII than U. intestinalis. Furthermore, energy dissipation via non photochemical quenching (NPQ) and state transitions showed efficacious photoprotection solution especially in U. prolifera suffered from the severe stresses. Results in the present study suggested that U. prolifera's higher photosynthetic capacity would contribute to its free-floating proliferation, and efficacious photoprotection in addition to favorable oceanographic conditions and high nutrient levels support its growth and aggregation. PMID- 27386262 TI - Accumulation of heavy metals and human health risk assessment via the consumption of freshwater fish Mastacembelus armatus inhabiting, thermal power plant effluent loaded canal. AB - Bioaccumulation of six heavy metals (Mn, Fe, Co, Ni, Cu, Zn) in the muscle of highly consumed fish species (Mastacembelus armatus) were measured using atomic absorption spectrometer. Fe (213.29 mg/kg dry weight) concentration was the most, followed by Zn (186.19 mg/kg dry weight), Ni (58.98 mg/kg dry weight), Cu (41.36 mg/kg dry weight), Co (9.06 mg/kg dry weight) and Mn (9.03 mg/kg dry weight). Estimated daily intake of heavy metals was calculated by mean fish consumption rate 19.5 * 10(-3) kg/day, on the basis of a calculation of the amount of fish consumed by adult individuals (male and female). The studied fish species pose non carcinogenic risk for Co and Ni [target hazard quotient (THQ) > 1] only. Hazard index (HI) was high. Carcinogenic risk (TR) posed by this fish for male and female was 3.43 * 10(-3) and 3.91 * 10(-3), respectively for Ni (the carcinogenic potency slope factor was available for Ni only). The study is an alert indicating that inhabitants who consume these fishes (particularly females) were at risk of Co and Ni toxicity. In India recommended guidelines have yet not been established for these heavy metals, which is essential for setting of toxicological standards. PMID- 27386264 TI - Risk analysis of gravity dam instability using credibility theory Monte Carlo simulation model. AB - Risk analysis of gravity dam stability involves complicated uncertainty in many design parameters and measured data. Stability failure risk ratio described jointly by probability and possibility has deficiency in characterization of influence of fuzzy factors and representation of the likelihood of risk occurrence in practical engineering. In this article, credibility theory is applied into stability failure risk analysis of gravity dam. Stability of gravity dam is viewed as a hybrid event considering both fuzziness and randomness of failure criterion, design parameters and measured data. Credibility distribution function is conducted as a novel way to represent uncertainty of influence factors of gravity dam stability. And combining with Monte Carlo simulation, corresponding calculation method and procedure are proposed. Based on a dam section, a detailed application of the modeling approach on risk calculation of both dam foundation and double sliding surfaces is provided. The results show that, the present method is feasible to be applied on analysis of stability failure risk for gravity dams. The risk assessment obtained can reflect influence of both sorts of uncertainty, and is suitable as an index value. PMID- 27386263 TI - Interleukin-21 plays a critical role in the pathogenesis and severity of type I autoimmune hepatitis. AB - BACKGROUND AND AIMS: Recently, the number of follicular helper T (Tfh) cells expressing interleukin (IL)-21 was found to increase in peripheral blood of human and murine models of autoimmune hepatitis (AIH). IL-21, the most recently discovered member of the type-I cytokine family, exerts various effects on the immune system, including B cell activation, plasma cell differentiation, and immunoglobulin production. We aimed to assess the relationship of serum IL-21 levels in patients with type I AIH with clinical and laboratory parameters and histology. METHODS: Ninety-two Japanese patients with liver disease (22 AIH, 20 primary biliary cholangitis, 19 drug-induced liver injury, 8 acute hepatitis B, 8 chronic hepatitis C, 10 non-alcoholic steatohepatitis, 5 viral hepatitis) and 10 healthy volunteers were recruited. Serum IL-21 levels were detected by enzyme linked immunosorbent assay. Real-time polymerase chain reaction measured mRNA levels of Bcl-6, IL-21, and CXCR5 (Tfh-related factors) in peripheral mononuclear cells. RESULTS: Mean age at diagnosis of AIH was 58.6 years, male-to-female ratio was 4:18, 18.2 % of participants had cirrhosis, and 22.7 % had severe disease. IL 21 levels were significantly increased in the serum of patients with AIH compared to those with other liver diseases and controls (p < 0.0001). Particularly, serum IL-21 levels were significantly increased in severe AIH cases compared to non severe cases (p < 0.05). Serum IL-21 levels correlated positively with total serum bilirubin levels (r = 0.46, p < 0.05), grading of necroinflammatory activity (r = 0.68, p < 0.005) and negatively with serum albumin levels in patients with AIH (r = -0.49, p < 0.05). In patients with biochemical remission of AIH, serum IL-21 levels remained elevated and correlated positively with serum IgG levels (r = 0.84, p < 0.01). Expression of Tfh-related factors, such as Bcl-6 and IL-21, in peripheral blood mononuclear cells of patients with AIH was significantly higher than that in healthy volunteers. CONCLUSIONS: IL-21 may play an important role in the pathogenesis and severity of AIH, and may present a promising target for AIH therapy. PMID- 27386265 TI - Increased expression of Tbet in CD4(+) T cells from clinically isolated syndrome patients at high risk of conversion to clinically definite MS. AB - BACKGROUND: The ability to identify clinically isolated syndrome (CIS) patients at high risk of progression to clinically definite multiple sclerosis (CDMS) would be clinically beneficial. The initiation of T cell mediated autoimmune diseases such as multiple sclerosis (MS) requires the initial inappropriate activation and differentiation of auto-reactive CD4(+) T cells. The quiescence of naive T cells is actively maintained by molecules such as TOB1, which control the threshold of activation. Upon activation, CD4(+) T cells can differentiate into various subsets depending on the milieu present. Th1 and Th17 cells are strongly implicated in MS, while regulatory T (Treg) cells constrain autoimmune inflammation and prevent autoimmunity. FINDINGS: We therefore investigated the expression of TOB1, CD44 and Treg, Th1 and Th17 transcription factors in relation to CIS progression. The expression of TOB1, CD44, FOXP3, TBX21 and RORC genes were measured in CD4(+) T cells from 10 healthy controls, 20 CIS patients within 3 months of initial clinical presentation and 10 relapsing remitting MS patients sampled within 2 months of relapse. CIS patients were subsequently grouped into those who converted to CDMS within 1 year and those who remained CIS. No differences in the expression of TOB1, CD44, FOXP3 and RORC were observed. There was a significant increase in the expression of the Th1 transcription factor Tbet, encoded by TBX21, in CIS patients that converted within 1 year compared with those who did not. CONCLUSION: This pilot data suggests a role for Th1 cells in CIS progression and warrants further evaluation in a larger cohort. PMID- 27386266 TI - Automated volumetric breast density estimation out of digital breast tomosynthesis data: feasibility study of a new software version. AB - BACKGROUND: A new software version of VolparaDensity (Volpara Algorithm version 1.5.1) is capable of calculating volumetric breast density (VBD) using either full-field digital mammography (FFDM) or digital breast tomosynthesis (DBT) images. In this preliminary study, we evaluated the feasibility and consistency of this new automated software. FINDINGS: Raw data from both DBT and FFDM were acquired from women breast cancer screening at our institution between April and August 2015 using. The DBT and FFDM images obtained under a single compression were collected and VBD was measured using fully automated software. A paired t test was used to analyze differences in the VBD calculated from paired FFDM and DBT images. The correlation coefficient (R value) was calculated and p < 0.05 was considered significant. Dualmodality images were acquired in 160 women; VBD data were available for all but one. There was a significant difference in the VBD of individual breasts calculated from DBT and FFDM and when data were compared per case (<0.001 and p = 0.006, respectively). There were very good to excellent correlations between data from FFDM and from DBT (R = 0.78, p < 0.0001; per breast, R = 0.89, p < 0.0001, per case, R = 0.91, p < 0.0001). CONCLUSIONS: VBD from DBT was well correlated to that from FFDM, though significant differences were observed between the two. PMID- 27386267 TI - Breast findings incidentally detected on body MRI. AB - OBJECTIVES: To evaluate breast findings incidentally detected on body MRI. METHODS: A retrospective review of the institutional database identified 1752 body MRI performed between January 2015 and September 2015. MRI of women with breast tissue visible in the field-of-view were reviewed for breast findings. Breast findings were classified with the breast imaging reporting and data system (BI-RADS) lexicon. The standard statistic, costs of additional work-up, and the clinical relevance were used to describe breast findings, and we calculated 95 % exact confidence intervals (CIs). RESULTS: 440 body MRI of 440 women (mean age: 57 +/- 20 years) included breast tissue in the field-of-view. A total of 41 breast findings were identified in 41 patients. Breast findings were classified BI-RADS 2 N = 25, BI-RADS 3 N = 13, BI-RADS 4 N = 3. A total of 3.6 % [95 % CI 1.6 %, 5.6 %] women with breast tissue visible on MRI had a recommendation for further imaging work-up for a breast finding. The 18.7 % (3 of 16) of these patients had a clinically important finding (breast cancer). Further imaging evaluation increased costs of ?108.3 per patient with a breast finding. CONCLUSIONS: Clinically important breast findings could be detected on body MRI in up to 0.7 % (3 of 440) of women. PMID- 27386268 TI - Extensive ischemic ulcers due to limb occlusion after endovascular aneurysm repair: a case report. AB - INTRODUCTION: Limb occlusion after endovascular aneurysm repair (EVAR) is a well known complication. However, extensive ischemic ulcers due to limb occlusion are extremely rare. CASE DESCRIPTION: We report a rare case of extensive ischemic ulcers that developed seven months after EVAR in an 85-year-old Japanese man. He had been taking appropriate anticoagulant therapy because of paroxysmal atrial fibrillation. Angiography showed a left limb occlusion and superficial femoral artery (SFA) chronic total occlusion (CTO), and intravascular ultrasound showed limb kinking. Endovascular therapy (EVT) was performed, and stent placement was used to cover a large amount of thrombi and correct the limb kinking, leading to complete recovery of left limb blood flow. After additional EVT was performed for the SFA CTO, outflow improved and the ulcers healed completely. DISCUSSION AND EVALUATION: It seemed that the combination of poor inflow and poor outflow led to limb thrombosis. CONCLUSIONS: Here, we describe an extremely rare case of extensive ischemic ulcers due to limb occlusion after EVAR. Patients should undergo careful follow-up after EVAR to monitor blood flow to the lower extremities. Additionally, the early detection and correction of limb kinking and poor outflow are essential to prevent the development of ischemic ulcers. PMID- 27386269 TI - A probabilistic bridge safety evaluation against floods. AB - To further capture the influences of uncertain factors on river bridge safety evaluation, a probabilistic approach is adopted. Because this is a systematic and nonlinear problem, MPP-based reliability analyses are not suitable. A sampling approach such as a Monte Carlo simulation (MCS) or importance sampling is often adopted. To enhance the efficiency of the sampling approach, this study utilizes Bayesian least squares support vector machines to construct a response surface followed by an MCS, providing a more precise safety index. Although there are several factors impacting the flood-resistant reliability of a bridge, previous experiences and studies show that the reliability of the bridge itself plays a key role. Thus, the goal of this study is to analyze the system reliability of a selected bridge that includes five limit states. The random variables considered here include the water surface elevation, water velocity, local scour depth, soil property and wind load. Because the first three variables are deeply affected by river hydraulics, a probabilistic HEC-RAS-based simulation is performed to capture the uncertainties in those random variables. The accuracy and variation of our solutions are confirmed by a direct MCS to ensure the applicability of the proposed approach. The results of a numerical example indicate that the proposed approach can efficiently provide an accurate bridge safety evaluation and maintain satisfactory variation. PMID- 27386270 TI - Cup implantation accuracy using the HipCOMPASS mechanical intraoperative support device. AB - BACKGROUND: While navigation systems have been developed to increase implantation accuracy in total hip arthroplasty (THA), they are not yet sufficiently versatile or commonly used. Therefore, to elevate the appeal of such systems, we have developed HipCOMPASS, a simple and effective mechanical angle indicator for use in supine THA. QUESTIONS/PURPOSES: How accurate is the mean cup orientation [in terms of errors in radiographic anteversion (RA) and inclination (RI)] in cases where HipCOMPASS is used for intraoperative support? Does HipCOMPASS increase this cup orientation accuracy compared to THA cases without it? Does HipCOMPASS increase mean operation time? METHODS: We measured cup orientation in 97 THA cases with HipCOMPASS and in 80 cases without it. Then we compared the angles determined in preoperative planning with the angles revealed by postoperative computed tomography (CT) for both groups. The discrepancy between them was defined as an error. Errors greater than 10 degrees were considered outliers. Additionally, mean operative time with and without the Hip COMPASS were compared. RESULTS: With the use of HipCOMPASS, the mean absolute error values in radiographic anteversion and inclination were 2.9 degrees +/- 2.3 degrees (range 0 degrees -12.8 degrees ) and 2.9 degrees +/- 2.1 degrees (0.1 degrees 7.7 degrees ), respectively. In contrast, without the use of HipCOMPASS, radiographic anteversion and inclination error values were 8.8 degrees +/- 5.8 degrees (0.1 degrees -25.4 degrees ) and 6.1 degrees +/- 4.5 degrees (0.2 degrees -21.0 degrees ), respectively. Outlier occurrence rates were 1.0 % with HipCOMPASS and 48.8 % without it. Mean operative times with and without HipCOMPASS use were 109.2 +/- 23.8 min (74-199 min) and 137.6 +/- 40.6 min (71 298 min), respectively. CONCLUSIONS: The study has found that HipCOMPASS dramatically increases implantation accuracy and it is also a simple and highly versatile tool that can be implemented quickly. Given its low cost in addition to its favourable accuracy, simple implementation, and short operative time, HipCOMPASS can be regarded as a very useful and effective THA support device. LEVEL OF EVIDENCE: Retrospective comparative study, Level 3. PMID- 27386271 TI - History, problems, and prospects of Islamic insurance (Takaful) in Bangladesh. AB - This study explains the history, current problems, and future possibilities of Islamic insurance (takaful) in Bangladesh. To articulate these issues, the researcher has adopted the qualitative method, and data has been collected through secondary sources i.e. articles, books, and online resources. The study reveals that Islamic insurance in Bangladesh is regulated by the Insurance Act 2010 which is contradictory with Islamic insurance causing numerous problems for Islamic insurance. This study also points out that Islamic insurance is a fast growing industry with huge prospects in Bangladesh. The government should introduce separate regulations for both Islamic and conventional insurance. The research concludes with suggestions for the further development of Islamic insurance in Bangladesh. PMID- 27386273 TI - Newton-Raphson preconditioner for Krylov type solvers on GPU devices. AB - A new Newton-Raphson method based preconditioner for Krylov type linear equation solvers for GPGPU is developed, and the performance is investigated. Conventional preconditioners improve the convergence of Krylov type solvers, and perform well on CPUs. However, they do not perform well on GPGPUs, because of the complexity of implementing powerful preconditioners. The developed preconditioner is based on the BFGS Hessian matrix approximation technique, which is well known as a robust and fast nonlinear equation solver. Because the Hessian matrix in the BFGS represents the coefficient matrix of a system of linear equations in some sense, the approximated Hessian matrix can be a preconditioner. On the other hand, BFGS is required to store dense matrices and to invert them, which should be avoided on modern computers and supercomputers. To overcome these disadvantages, we therefore introduce a limited memory BFGS, which requires less memory space and less computational effort than the BFGS. In addition, a limited memory BFGS can be implemented with BLAS libraries, which are well optimized for target architectures. There are advantages and disadvantages to the Hessian matrix approximation becoming better as the Krylov solver iteration continues. The preconditioning matrix varies through Krylov solver iterations, and only flexible Krylov solvers can work well with the developed preconditioner. The GCR method, which is a flexible Krylov solver, is employed because of the prevalence of GCR as a Krylov solver with a variable preconditioner. As a result of the performance investigation, the new preconditioner indicates the following benefits: (1) The new preconditioner is robust; i.e., it converges while conventional preconditioners (the diagonal scaling, and the SSOR preconditioners) fail. (2) In the best case scenarios, it is over 10 times faster than conventional preconditioners on a CPU. (3) Because it requries only simple operations, it performs well on a GPGPU. In addition, the research has confirmed that the new preconditioner improves the condition of matrices from a mathematical point of view by calculating the condition numbers of preconditioned matrices, as anticipated by the theoretical analysis. PMID- 27386272 TI - Different settings of place of midwife-led birth: evaluation of a midwife-led birth centre. AB - OBJECTIVES: The claimed advantages of home deliveries, including fewer medical interventions, are potentially counter balanced by the small additional risk on perinatal adverse outcome compared to hospital deliveries in low risk women. Homelike birth centres have been proposed a new setting for low risk women combining the advantages of home and hospital, resulting in lower intervention rates with equal safety. This paper addresses whether the introduction of a midwife-led birth centre adjacent to the hospital combines the advantages of home and hospital deliveries. Additionally, we investigate whether the introduction of a midwife-led birth centre leads to a different risk selection of women planning their delivery either at home, at the hospital or at the birth centre. METHODS: Anonymized data, between January 2007 and June 2012, was collected from the four participating midwife practices. Women (n = 5558) were categorized according to intended place of birth. Women's characteristics and pregnancy outcomes were compared between the period before and after its introduction using Chi square and Fisher's Exact tests. Direct and indirect standardized rates were calculated for different outcomes [(1) intrapartum and neonatal mortality (<24 h), (2) composite outcome of neonatal morbidities, (3) composite outcome of maternal morbidities, and (4) medical intervention], taking the period before introduction as reference. RESULTS: After the introduction of the birth centre a different risk selection was observed. Women's characteristics were most unfavourable for intended birth centre births. Additionally, an higher neonatal risk load was seen within these women. After its introduction neonatal morbidities decreased (5.0 vs. 3.8 %) and maternal morbidities decreased (8.3 vs. 7.3 %). Interventions were about equal. Direct and indirect standardization provided similar results. CONCLUSION: Neonatal morbidity and maternal morbidity tended to decrease, while overall intervention rates were unaffected. The introduction of the midwife-led birth centre seems to benefit the outcome of midwife-led deliveries. We interpret this change by the redistribution of the higher risk women among the low risk population intending birth at the birth centre instead of home. PMID- 27386274 TI - Response of a Mu-class glutathione S-transferase from black tiger shrimp Penaeus monodon to aflatoxin B1 exposure. AB - Glutathione S-transferases (GSTs) are a family of multifunctional phase II enzymes that are involved in the detoxification of exogenous and endogenous compounds. In this study, a full-length cDNA of Mu-class GST (PmMuGST) was isolated from the hepatopancreas of Penaeus monodon using rapid amplification of cDNA ends method. The full length cDNA of PmMuGST is 867 bp, contains an open read frame of 660 bp, and encodes a polypeptide of 219 amino acids with a molecular mass of 25.61 kDa and pI of 6.15. Sequence analysis indicated that the predicted protein sequence of PmMuGST was very similar to (86 %) that of Litopenaeus vannamei. A conserved domain of GST_N_Mu_like (PSSM: cd03075) and GST_C_family_superfamily_like (PSSM: cl02776) was indentified in PmMuGST. Real time quantitative RT-PCR analysis indicated that PmMuGST was present in all of the tested tissues. PmMuGST transcripts both in the hepatopancreas and in the muscle were significantly induced after 14 days of treatment with a low dosage of AFB1 (50 MUg/kg) exposure and were significantly inhibited after 42 and 56 days of a high dosage of AFB1 (1000, 2500 MUg/kg AFB1) exposure. Taken together, the Mu-class GST from P. monodon was inducible and was involved in the response to AFB1 exposure. PMID- 27386275 TI - Interactive music composition driven by feature evolution. AB - Evolutionary music composition is a prominent technique for automatic music generation. The immense adaptation potential of evolutionary algorithms has allowed the realisation of systems that automatically produce music through feature and interactive-based composition approaches. Feature-based composition employs qualitatively descriptive music features as fitness landmarks. Interactive composition systems on the other hand, derive fitness directly from human ratings and/or selection. The paper at hand introduces a methodological framework that combines the merits of both evolutionary composition methodologies. To this end, a system is presented that is organised in two levels: the higher level of interaction and the lower level of composition. The higher level incorporates the particle swarm optimisation algorithm, along with a proposed variant and evolves musical features according to user ratings. The lower level realizes feature-based music composition with a genetic algorithm, according to the top level features. The aim of this work is not to validate the efficiency of the currently utilised setup in each level, but to examine the convergence behaviour of such a two-level technique in an objective manner. Therefore, an additional novelty in this work concerns the utilisation of artificial raters that guide the system through the space of musical features, allowing the exploration of its convergence characteristics: does the system converge to optimal melodies, is this convergence fast enough for potential human listeners and is the trajectory to convergence "interesting' and "creative" enough? The experimental results reveal that the proposed methodological framework represents a fruitful and robust, novel approach to interactive music composition. PMID- 27386276 TI - Towards early software reliability prediction for computer forensic tools (case study). AB - Versatility, flexibility and robustness are essential requirements for software forensic tools. Researchers and practitioners need to put more effort into assessing this type of tool. A Markov model is a robust means for analyzing and anticipating the functioning of an advanced component based system. It is used, for instance, to analyze the reliability of the state machines of real time reactive systems. This research extends the architecture-based software reliability prediction model for computer forensic tools, which is based on Markov chains and COSMIC-FFP. Basically, every part of the computer forensic tool is linked to a discrete time Markov chain. If this can be done, then a probabilistic analysis by Markov chains can be performed to analyze the reliability of the components and of the whole tool. The purposes of the proposed reliability assessment method are to evaluate the tool's reliability in the early phases of its development, to improve the reliability assessment process for large computer forensic tools over time, and to compare alternative tool designs. The reliability analysis can assist designers in choosing the most reliable topology for the components, which can maximize the reliability of the tool and meet the expected reliability level specified by the end-user. The approach of assessing component-based tool reliability in the COSMIC-FFP context is illustrated with the Forensic Toolkit Imager case study. PMID- 27386277 TI - Generally recognized as safe (GRAS) Lactococcus lactis strains associated with Lippia sidoides Cham. are able to solubilize/mineralize phosphate. AB - Eight strains isolated from the stems of Lippia sidoides were identified as belonging to Lactococcus lactis, a bacterial species considered as "generally recognized as safe". Their capacity to solubilize/mineralize phosphate was tested in vitro with different inorganic and organic phosphorus (P) sources. All strains were able to solubilize calcium phosphate as an inorganic P source, and the best result was observed with strain 003.41 which solubilized 31 % of this P source. Rock phosphate, a mined rock containing high amounts of phosphate bearing minerals, was solubilized by five strains. When calcium phytate was the organic P source used, the majority of the strains tested showed phosphate mineralization activity. Moreover, all strains were able to solubilize/mineralize phosphate from poultry litter, a complex P source containing inorganic and predominantly organic P. The presence of genes coding for phytase and alkaline phosphatase was searched within the strains studied. However, only gene sequences related to alkaline phosphatase (phoA and phoD) could be detected in the majority of the strains (excepting strain 006.29) with identities varying from 67 to 88 %. These results demonstrate for the first time the potential of L. lactis strains for phosphate solubilization/mineralization activity using a broad spectrum of P sources; therefore, they are of great importance for the future development of more safe bioinoculants with possible beneficial effects for agriculture. PMID- 27386278 TI - The relationship between quantitative measures of disc height and disc signal intensity with Pfirrmann score of disc degeneration. AB - PURPOSE: To assess the relationship between quantitative measures of disc height and signal intensity with the Pfirrmann disc degeneration scoring system and to test the inter-rater reliability of the quantitative measures. METHODS: Participants were 76 people who had recently recovered from their last episode of acute low back pain and underwent MRI scan on a single 3T machine. At all 380 lumbar discs, quantitative measures of disc height and signal intensity were made by 2 independent raters and compared to Pfirrmann scores from a single radiologist. For quantitative measures of disc height and signal intensity a "raw" score and 2 adjusted ratios were calculated and the relationship with Pfirrmann scores was assessed. The inter-tester reliability of quantitative measures was also investigated. RESULTS: There was a strong linear relationship between quantitative disc signal intensity and Pfirrmann scores for grades 1-4, but not for grades 4 and 5. For disc height only, Pfirrmann grade 5 had significantly reduced disc height compared to all other grades. Results were similar regardless of whether raw or adjusted scores were used. Inter-rater reliability for the quantitative measures was excellent (ICC > 0.97). CONCLUSIONS: Quantitative measures of disc signal intensity were strongly related to Pfirrmann scores from grade 1 to 4; however disc height only differentiated between grade 4 and 5 Pfirrmann scores. Using adjusted ratios for quantitative measures of disc height or signal intensity did not significantly alter the relationship with Pfirrmann scores. PMID- 27386279 TI - Farmers' perception and adaptation practice to climate variability and change: a case study of the Vea catchment in Ghana. AB - BACKGROUND: Rain-fed agriculture remains the source of employment for a majority of Ghana's population, particularly in northern Ghana where annual rainfall is low. The purpose of this study is to examine farmers' perceptions and adaptation practices to climate change and variability in accordance with actual recorded weather data of the Vea catchment in Upper East Region of northern Ghana during the time interval from 1972 to 2012. METHODS: Climatic data over 41-years (1972 2012) from four stations in vicinity of the catchment was evaluated to identify actual weather outcomes. A survey questionnaire targeting farmers with at least 30-years of farming experience in the area was administered in six of the eleven agricultural enumeration areas in the catchment covering 305 km(2). Of the 466 farmers interviewed, 79 % utilized rain-fed practices while 21 % utilized some form of irrigation. RESULTS: Results indicate that nearly 90 % of the farmers interviewed believe that temperature increased over the past 30-years, while over 94 % of the farmers believe that amount of rainfall, duration, intensity and rainy days has decreased. Nearly 96 % of the farmers believe that their farms are extremely vulnerable to decreased rainfall, droughts and changed timing of rainfall events. Climatic data of the catchment indicates a rising trend in temperature but no long-term changes in annual and monthly rainfall, thereby possibly increasing levels of evapotranspiration. While no statistical differences were found between rain-fed and irrigation agricultural types regarding receipt of external support, their approaches to climatic change adaptation do differ. Patently, 94 and 90 % of farmers relying on rain-fed and irrigation strategies respectively receive some form of support, primarily via extension services. Farmers using rain-fed practices adjust to climate variability by varying crop types via rotation without fertilizer while farmers employing irrigation practices are more likely to offset climate variability with a greater use of fertilizer application. CONCLUSION: The Vea catchment faces rising temperature and evapotranspiration trends. Farmers are aware of these climatic changes and are adapting strategies to cope with the effects but require support. Adequate extension services and irrigation facilities are needed to assist farmers in order to sustain their livelihoods on the long run. PMID- 27386280 TI - Vertical transportation systems embedded on shuffled frog leaping algorithm for manufacturing optimisation problems in industries. AB - Response surface methods via the first or second order models are important in manufacturing processes. This study, however, proposes different structured mechanisms of the vertical transportation systems or VTS embedded on a shuffled frog leaping-based approach. There are three VTS scenarios, a motion reaching a normal operating velocity, and both reaching and not reaching transitional motion. These variants were performed to simultaneously inspect multiple responses affected by machining parameters in multi-pass turning processes. The numerical results of two machining optimisation problems demonstrated the high performance measures of the proposed methods, when compared to other optimisation algorithms for an actual deep cut design. PMID- 27386281 TI - An efficient classification method based on principal component and sparse representation. AB - As an important application in optical imaging, palmprint recognition is interfered by many unfavorable factors. An effective fusion of blockwise bi directional two-dimensional principal component analysis and grouping sparse classification is presented. The dimension reduction and normalizing are implemented by the blockwise bi-directional two-dimensional principal component analysis for palmprint images to extract feature matrixes, which are assembled into an overcomplete dictionary in sparse classification. A subspace orthogonal matching pursuit algorithm is designed to solve the grouping sparse representation. Finally, the classification result is gained by comparing the residual between testing and reconstructed images. Experiments are carried out on a palmprint database, and the results show that this method has better robustness against position and illumination changes of palmprint images, and can get higher rate of palmprint recognition. PMID- 27386282 TI - Ideals and primitive elements of some relatively free Lie algebras. AB - Let F be a free Lie algebra of finite rank over a field K. We prove that if an ideal [Formula: see text] of the algebra [Formula: see text] contains a primitive element [Formula: see text] then the element [Formula: see text] is primitive. We also show that, in the Lie algebra [Formula: see text] there exists an element [Formula: see text] such that the ideal [Formula: see text] contains a primitive element [Formula: see text] but, [Formula: see text] and [Formula: see text] are not conjugate by means of an inner automorphism. PMID- 27386283 TI - Measuring the operational efficiency of individual theme park attractions. AB - This study assesses the operation efficiency of theme park attractions using the data envelopment analysis, utilizing actual data on 15 attractions at Samsung Everland located in Yongin-si, Republic of Korea. In particular, this study identifies crowding and waiting time as one of the main causes of visitor's satisfaction, and analyzes the efficiency of individual attractions in terms of waiting time. The installation area, installation cost, and annual repair cost are set as input factors and the number of annual users and customer satisfaction as output factors. The results show that the roller coaster-type attractions were less efficient than other types of attractions while rotating-type attractions were relatively more efficient. However, an importance performance analysis on individual attraction's efficiency and satisfaction showed that operational efficiency should not be the sole consideration in attraction installation. In addition, the projection points for input factors for efficient use of attractions and the appropriate reference set for benchmarking are provided as guideline for attraction efficiency management. PMID- 27386284 TI - Three-dimensional reconstruction of vascular arrangement including the hepatic artery and left gastric vein during gastric surgery. AB - BACKGROUND: During gastric surgery, precise recognition of the anatomical variations and relationships among gastric tumors and vessels, including the hepatic artery (HA) and left gastric vein (LGV), is required. We utilized a three dimensional (3D) reconstructed image as a preoperative simulation for gastric surgery. METHODS: We retrospectively analyzed 84 patients who underwent gastrectomy at Tsukuba Medical Center Hospital. This cohort was sequentially divided into a without-3D group (n = 42) and with-3D group (n = 42), and the perioperative outcomes were compared. The 3D image could be used to classify the HA or LGV arrangement pattern. RESULTS: Regarding the HA arrangement, the right HA of 1 patient (2.3 %) was arising from the superior mesenteric artery, the left HA of 8 patients (19 %) was arising from the left gastric artery, 29 patients (69 %) presented a normal rearrangement, and 4 patients (9.5 %) exhibited other arrangements. The analysis of the LGV arrangement revealed that the LGV in 15 patients (36 %) was located on the dorsal side of the common HA, the LGV in 5 patients (12 %) was located on the ventral side of the common HA, the LGV in 12 patients (29 %) was found on the ventral side of the splenic artery, the LGV in 6 patients (14 %) was located on the dorsal side of the splenic artery, and 4 patients (9.5 %) presented other arrangements. The intraoperative blood loss in the without-3D and with-3D groups was 276 +/- 430 and 157 +/- 170 g, respectively (p = 0.027). CONCLUSIONS: The 3D reconstruction technique was useful for understanding and sharing anatomic information during gastric surgery. PMID- 27386286 TI - Chemical characterization of carbonaceous carbon from industrial and semi urban site of eastern India. AB - Rigorous campaign was carried out from July 2013 to June 2014 at the remote and industrial site (Adityapur and Seraikela Kharsawan) in the eastern India aiming to identify and quantify the changes of aerosol chemical composition in the presence of industrial and biomass burning influence. The 24-h PM10 filter samples were analyzed by mass, carbonaceous species, organic ions. The results suggested that the average PM10 concentrations were 165 +/- 43.93, 141 +/- 30.86 MUg/m(3) in industrial and remote site respectively. Secondary organic ions (SOC) were the dominant pollutants of PM10. Total carbon was a significant component explaining above 15 % of PM10. The annual average mass concentration of EC, OC, WSOC 26.39 +/- 4.56, 5.11 +/- 1.82, 18.56 +/- 5.30 and 16.27 +/- 5.75, 7.70 +/- 2.1, 9.65 +/- 1.92 ug/m(3), OC/EC, WSOC/OC 5.29 +/- 1.08, 0.71 +/- 0.17 and 2.34 +/- 0.75, 0.67 +/- 0.16) of industrial and remote site were respectively; and OC/EC particularly in industrial site it reached the highest 5.29 +/- 1.08 which demonstrated that SOC should be a significant composition of PM10. The mass fraction of the highlighted species varies seasonally, resulting the air mass trajectories and corresponding cause severe strength. Based on exact mass concentration ratios of EC/OC, WSOC/OC, we predicted that industries and biofuel/biomass burning are a major source of atmospheric aerosols in the eastern part of India. This study provides the scientific baseline data of carbonaceous aerosols for eastern Jharkhand, India. PMID- 27386285 TI - Quality of Life in Spanish advanced non-small-cell lung cancer patients: determinants of global QL and survival analyses. AB - PURPOSE: This paper studies the Quality of Life (QL) of Spanish advanced non small-cell lung cancer (NSCLC) patients receiving platinum-doublet chemotherapy, compares our results with those from studies from other cultural areas, and identifies factors associated with global QL and survival prognostic variables. METHODS: EORTC QLQ-C30 and QLQ-LC13 questionnaires were completed three times by 39 patients along treatment and follow-up. Univariate and multivariate logistic regression analyses were performed to study global QL determinants (<=50 points considered low global-QL score). Analyses of prognostic variables for death were performed (Cox proportional hazards models). RESULTS: QL mean scores in the whole sample were moderately high, with limitations (>30) in physical, role, social functioning, emotional areas, fatigue, pain, neuropathy and global QL. Differences with studies from other cultural areas were mainly found in the lower score for dyspnoea (>=15 points). There were no significant differences in QL scores between the first and second assessments. In six areas, the third assessment was lower than the first and second: fatigue, hair loss (>20 points); physical, social functioning, neuropathy (10-20 points); emotional functioning (5 10 points). The best model to explain the chances of low QL includes, as explanatory variables, high emotional functioning as protective factor and fatigue as risk factor (R(2) = 0.70). Eight QL areas (four pain-related) and performance status showed a statistically significant association with survival. CONCLUSION: Patients adapted well to their disease and treatments. Platinum doublet can be administered in advanced NSCLC patients. Our QL data are in line with those from other cultural areas. PMID- 27386287 TI - Effect of heat wave at the initial stage in spark plasma sintering. AB - Thermal effects are important considerations at the initial stage in spark plasma sintering of non-conductive Al2O3 powders. The generalized thermo-elastic theory is introduced to describe the influence of the heat transport and thermal focusing caused by thermal wave propagation within a constrained space and transient time. Simulations show that low sintering temperature can realize high local temperature because of the superposition effect of heat waves. Thus, vacancy concentration differences between the sink and the cross section of the particles increase relative to that observed during pressure-less and hot pressure sintering. Results show that vacancy concentration differences are significantly improved during spark plasma sintering, thereby decreasing the time required for sintering. PMID- 27386288 TI - A production planning model considering uncertain demand using two-stage stochastic programming in a fresh vegetable supply chain context. AB - Production planning models are achieving more interest for being used in the primary sector of the economy. The proposed model relies on the formulation of a location model representing a set of farms susceptible of being selected by a grocery shop brand to supply local fresh products under seasonal contracts. The main aim is to minimize overall procurement costs and meet future demand. This kind of problem is rather common in fresh vegetable supply chains where producers are located in proximity either to processing plants or retailers. The proposed two-stage stochastic model determines which suppliers should be selected for production contracts to ensure high quality products and minimal time from farm to-table. Moreover, Lagrangian relaxation and parallel computing algorithms are proposed to solve these instances efficiently in a reasonable computational time. The results obtained show computational gains from our algorithmic proposals in front of the usage of plain CPLEX solver. Furthermore, the results ensure the competitive advantages of using the proposed model by purchase managers in the fresh vegetables industry. PMID- 27386289 TI - Intervention on whole grain with healthy balanced diet to manage childhood obesity (GReat-ChildTMtrial): study protocol for a quasi-experimental trial. AB - BACKGROUND: The rapid increase in childhood obesity is a serious public health problem, and has led to the development of many interventions. However, no intervention has emphasized whole grains as a strategy to manage childhood obesity. Therefore, this article describes the protocol of a 12-week multi component, family-based intervention on whole grain, using a healthy balanced diet for managing childhood obesity. METHODS: The GReat-Child trial utilize a quasi-experimental method in which two schools in Kuala Lumpur are assigned to intervention and control groups. The eligibility criteria are overweight/obese children, aged 9 through 11 years, who has no serious co-morbidities. The children who report consuming whole-grain foods in their 3-day diet-recall during the screening will be excluded. The study sample is characterized by anthropometric measurements (weight, height, percentage of body fat and waist circumference), whole grain and nutrient intakes (3-day 24-h diet recalls), and their knowledge, attitudes and practices towards whole grain. The 12-week intervention is comprised of three components addressing behaviour, personal and environmental factors, based on social cognitive theory: (1) individual diet counselling for the parents; (2) six 30-min nutrition education classes and (3) school delivery of whole-grain foods; The control school does not receive any interventions, however, for ethical purposes, a health talk is conducted after the entire GReat-Child Trial is completed. CONCLUSION: The GReat-Child trial represents a novel approach to examining the effectiveness of the intervention of whole grain in a healthy balanced diet on managing childhood obesity. We anticipate that this trial will reveal not only whether whole grain intervention will be effective in managing childhood obesity, but also provide greater insights into the acceptance of whole grain among Malaysian children. PMID- 27386290 TI - Detection of a numeric value predictive of increased dose to left anterior descending coronary artery (LAD) in radiotherapy of breast cancer. AB - PURPOSE: We have evaluated thoracic conformation of patients in order to derive a numeric value predictive of an increased dose to left anterior descending coronary artery (LAD), critical structure for the development of late radio induced cardiac morbidity. METHODS: We have evaluated 91 patients (36-88 years) affected by breast cancer stage I-II (Tis-T1-2 N0-1), undergoing adjuvant radiotherapy with conventional fractionation. For each patient on CT images was measured the distance between the back face of the sternum (manubrium) and the anterior face of body of the corresponding vertebra (a), and the distance measured on the line at 45 degrees between the vertebral body of the same vertebra and the back face of the rib corresponding (b). The a/b ratio showed values between 0.626 and 1.123. We used the median value (0.821) as cut-off to divide the patients in two groups. We calculated in both groups: Volume (Vol) heart, Vol LAD with an expansion of 0.6 mm; Dmean LAD (Gy); Dmax LAD (Gy); V10 V20-V30 (%) LAD and we correlated these values with parametric and non-parametric tests. RESULTS: The Pearson test has showed a statistically significant correlation between Vol breast and V10, V20, V30 with borderline significance (p = 0.006; p = 0.02; p = 0.05). The data were confirmed by testing non-parametric Kendall (tau = 0.004; tau = 0.015; tau = 0.016) and Spearman (rho = 0.003; rho = 0.016; rho = 0.015). We conducted categorizing into quartiles of breast volume and evaluated the correlation with a/b. We have found a significative correlation (p = 0.01) between small Vol breast (<=660.23 cc) and a/b < 0.0821 and greater Vol breast (>660.23 cc) with a/b > 0.0821. From the evaluation of the distribution of V10 in the two groups taking account of the Dmean <=5 or >5 significance was found with a/b; Chi square 0.009 (0.01). Values <=5 were observed in women with a/b < 0.0821. Values >5 in women with a/b > 0.0821. CONCLUSIONS: The geometric conformity of chest thorax considering a/b and the value of 0.0821 can reveals an important parameter in the selection of patients suitable for radiation therapy on left breast in order to evaluate the risk of late cardiac events. This consideration during treatment planning can change the technique or the set-up allowing the development of a customized plan. PMID- 27386291 TI - Evaluation of antibacterial activity of honey against multidrug resistant bacteria in Ayder Referral and Teaching Hospital, Northern Ethiopia. AB - BACKGROUND: Multidrug resistance is a global health issue. Hence integration of traditional medicine like honey and modern medicine could be a best option in the treatment of patients infected with drug resistant bacteria. Despite the multi floral and huge honey production in the region, there are no studies that evaluate the antibacterial activity of honey against multidrug resistant bacteria. OBJECTIVE: To evaluate the antibacterial activity of honey against multidrug resistant human pathogenic bacterial isolates of wound and ear infections. METHODS: Red and white honeys were obtained from three districts Eastern Zone of Tigray namely Temben, Atsbi and Samre. The antibacterial potential of these honeys was determined against multidrug resistant isolates of clinical isolates of bacterial species of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Coagulase negative Staphylococcus, Streptococcus pyogenes and Klebsiella pneumonia, and five controls bacterial using tube dilutions methods. Undiluted and twofold serial dilutions of honeys were tested to determine minimum inhibitory concentration (MIC) using broth tube dilution methods through visual inspection and minimum bactericidal concentration (MBC) was determined by sub-culturing tubes showing no visible sign of growth/turbidity in MIC. RESULTS: The mean MIC of red honeys for control and test bacteria was 7.7-8.9 and 12.6-17.9 % (v/v) respectively. Whilst the MIC of white honey was 12.2-12.5 % (v/v) for control and 16.1-27.7 % (v/v) for test bacteria. Mean MBC of red honeys for control and test isolates was from 25-40 to 30.4-62.5 % (v/v) respectively, and 40-55 and 60.7-75 % (v/v) for white honeys. Honey collected from Samre area has shown better antibacterial activity than other sites. Similarly red honeys from all areas were found to have better antibacterial activity against the multidrug bacteria than the white honey. Over all the MIC and MBC of all isolates was between 6.25-50 and 12.5-100 % (v/v) respectively. CONCLUSION: Red honey from all sites showed better antibacterial activity than the white honey. Likewise, honey from Samre area showed better antibacterial activity than Temben and Atsbi districts. All collected honeys showed varied bacteriostatic and bactericidal activities, and none of the isolates was resistant to tested honeys. PMID- 27386292 TI - A retrospective analysis of characteristics of visual field damage in patients with Leber's hereditary optic neuropathy. AB - The objective of this study is to investigate the characteristics and the evolution of visual field damage caused by Leber's hereditary optic neuropathy (LHON) and to provide clinical data for the diagnosis of LHON. Parameters of visual field in 32 consecutive patients (49 eyes) with LHON who were confirmed by genetic diagnostic tests were retrospectively measured within 1 week, between three to six months, and at six months after onset. Visual field defects revealed central scotoma in 26 eyes (53.1 %), paracentral scotoma in 12 eyes (24.5 %), ceco-central defects in 6 eyes (12.2 %), blind spot enlargenment in 3 eyes (6.1 %), quadrantanopia in 2 eyes (4.1 %) within 1 week after onset. After 3 to 6 months, ceco-central defects were detected in 22 eyes (44.9 %), central isopter constriction in 10 eyes (20.4 %), hemianopia or quadrantanopia in 5 eyes (10.2 %), central scotoma in 4 eyes (8.2 %), and paracentral scotoma in 1 eye (2.0 %). After 6 months, central isopter constriction was observed in 18 eyes (36.7 %), diffuse defects in 21 eyes (42.9 %), ceco-central defects in 3 eyes (6.1 %), hemianopia or quadrantanopia in 5 eyes (10.2 %), and central scotoma in 2 eyes (4.1 %). LHON at different stages was characterized by different focal visual field defects: visual field defects in LHON patients within 1 week after onset were mostly central or paracentral scotoma, which was enlarged around the ceco central defect, or connected to form a blind spot after 3-6 months. Diffuse and central isopter constriction defects were usually developed after 6 months. Damages firstly appeared in papillomacular bundle and gradually expanded outward. These characteristics of visual field defects reported in this study might provide a clinical basis for better diagnosis of LHON. PMID- 27386293 TI - Identification of new deep sea sinuous channels in the eastern Arabian Sea. AB - Deep sea channel systems are recognized in most submarine fans worldwide as well as in the geological record. The Indus Fan is the second largest modern submarine fan, having a well-developed active canyon and deep sea channel system. Previous studies from the upper Indus Fan have reported several active channel systems. In the present study, deep sea channel systems were identified within the middle Indus Fan using high resolution multibeam bathymetric data. Prominent morphological features within the survey block include the Raman Seamount and Laxmi Ridge. The origin of the newly discovered channels in the middle fan has been inferred using medium resolution satellite bathymetry data. Interpretation of new data shows that the highly sinuous deep sea channel systems also extend to the east of Laxmi Ridge, as well as to the west of Laxmi Ridge, as previously reported. A decrease in sinuosity southward can be attributed to the morphological constraints imposed by the elevated features. These findings have significance in determining the pathways for active sediment transport systems, as well as their source characterization. The geometry suggests a series of punctuated avulsion events leading to the present array of disconnected channels. Such channels have affected the Laxmi Basin since the Pliocene and are responsible for reworking older fan sediments, resulting in loss of the original erosional signature supplied from the river mouth. This implies that distal fan sediments have experienced significant signal shredding and may not represent the erosion and weathering conditions within the onshore basin at the time of sedimentation. PMID- 27386294 TI - Communication practices in the US and Syria. AB - This study highlights Syrian communication practices using comparative tests with the United States communication as a baseline. Additionally, theoretical findings on individualism and collectivism theory are extended to include findings from Syria. Multivariate Analysis of Covariance was used to test culture's effect in demographically similar (in age, SES, and education) student convenience samples, with the covariate communication adaptability, on dependent variables: empathy, social confirmation, social composure, friendships, non-verbal immediacy, social self-efficacy, and general self-efficacy. Results indicated that Syrians possess more empathy, social confirmation, and perceived general self-efficacy in comparison to U.S. citizens who have greater social composure, friendships, non verbal immediacy and social self-efficacy. These results indicate that Syrians have the strength of self-efficacy to succeed in intercultural relationships while U.S. Americans have the assets of warmth and sociability to enable successful interactions with Syrians. PMID- 27386295 TI - Comparison of the effects of Mitomycin-C and sodium hyaluronate/carboxymethylcellulose [NH/CMC] (Seprafilm) on abdominal adhesions. AB - INTRODUCTION: Intra-abdominal adhesions (IA) may occur after abdominal surgery and also may lead to complications such as infertility, intestinal obstruction and chronic pain. The aim of this study was to compare the effects of Mitomycin-C (MM-C) and sodium hyaluronate/carboxymethylcellulose [NH/CMC] on abdominal adhesions in a cecal abrasion model and to investigate the toxicity of MM-C on complete blood count (CBC) and bone marrow analyses. METHODS: The study comprised forty rats in four groups (Control, Sham, Cecal abrasion + MM-C, and Cecal abrasion + NH/CMC). On postoperative day 21, all rats except for the control (CBC + femur resection) group, were sacrificed. Macroscopical and histopathological evaluations of abdominal adhesions were performed. In order to elucidate the side effects of MM-C; CBC analyses and femur resections were performed to examine bone marrow cellularity. RESULTS: CBC analyses and bone marrow cellularity assessment revealed no statistically significant differences between MM-C, NH/CMC and control groups. No significant differences in inflammation scores were observed between the groups. The MM-C group had significantly lower fibrosis scores compared to the NH/CMC and sham groups. Although the adhesion scores were lower in the MM-C group, the differences were not statistically significant. CONCLUSION: Despite its potential for systemic toxicity, MM-C may show some anti fibrosis and anti-adhesive effects. MM-C is a promising agent for the prevention of IAs, and as such, further trials are warranted to study efficacy. PMID- 27386296 TI - Vulnerability and adaptation to climate change in the Comoe River Basin (West Africa). AB - Climate change is impacting water users in many sectors: water supply, farming, industry, hydropower, fishing, housing, navigation and health. Existing situations, like population growth, movement of populations from rural to urban areas, poverty and pollution can aggravate the impacts of climate change. The aim of the study is to evaluate the vulnerability of different water user groups to climate change and define communities' adaptation strategies in the Comoe River Basin. Information was collected on communities' concerns and perception on changes in climate and potential adaptation measures and strategies. Results show that 95 % of the sample in the study communities had heard of it and are aware that climate change is occurring. They have been experiencing changes in economic activity and cropping pattern, reduced water level in rivers, crop failure, delay in cropping season, new pests and diseases, food insecurity, drop in income and decline in crop yield. Results also show that communities employ various adaptation strategies including crops diversification, substitution and calendar redefinition, agroforestry, borrowing from friends and money lenders and increasing fertilizer application. PMID- 27386297 TI - Apparent diffusion coefficient value for estimating clinicohistological factors in bladder cancer including infiltration style and lymphatic invasion. AB - OBJECTIVE: To evaluate a role of apparent diffusion coefficient (ADC) values measured from diffusion-weighted imaging we investigated its association with clinicopathological tumor characteristics of bladder cancer. MATERIALS AND METHODS: Diffusion-weighted MRI at 1.5 Tesla using b-values of 0, 1000 s/mm(2) was taken before transurethral resection by 114 bladder urothelial tumor patients. ADC value was measured and its relationship with pathological factors including T stage, tumor grade, infiltration style (INF) and lymphatic invasion (ly) was analyzed. RESULTS: Median ADC value was significantly lower in Grade 3 than in Grade 1 (P < 0.001) or in Grade 2 (P = 0.002), in INFb than in INFa (P = 0.004), in INFc than in INFa (P < 0.001), in ly1 than in ly0 (P < 0.001) and lower in T2? than in T1? (P < 0.001), respectively. Receiver operating curve demonstrated the accuracy of detecting muscle invasive bladder cancer or ly+ by using area under curve (AUC), showing 0.758 and 0.748. CONCLUSION: ADC value is likely to serve as a useful biomarker showing clinicopathological characterictics of bladder cancer. PMID- 27386298 TI - Scale adaptive compressive tracking. AB - Recently, the compressive tracking (CT) method (Zhang et al. in Proceedings of European conference on computer vision, pp 864-877, 2012) has attracted much attention due to its high efficiency, but it cannot well deal with the scale changing objects due to its constant tracking box. To address this issue, in this paper we propose a scale adaptive CT approach, which adaptively adjusts the scale of tracking box with the size variation of the objects. Our method significantly improves CT in three aspects: Firstly, the scale of tracking box is adaptively adjusted according to the size of the objects. Secondly, in the CT method, all the compressive features are supposed independent and equal contribution to the classifier. Actually, different compressive features have different confidence coefficients. In our proposed method, the confidence coefficients of features are computed and used to achieve different contribution to the classifier. Finally, in the CT method, the learning parameter lambda is constant, which will result in large tracking drift on the occasion of object occlusion or large scale appearance variation. In our proposed method, a variable learning parameter lambda is adopted, which can be adjusted according to the object appearance variation rate. Extensive experiments on the CVPR2013 tracking benchmark demonstrate the superior performance of the proposed method compared to state-of the-art tracking algorithms. PMID- 27386299 TI - Dynamics of the functions [Formula: see text] with the real parameter. AB - In this paper, the dynamics of the functions [Formula: see text] with the real parameter is studied. We say that a real parameter [Formula: see text] belongs to the set [Formula: see text] for a positive integer n if [Formula: see text] has an attracting cycle of n-order. We prove that the Fatou set [Formula: see text] is a completely invariant attracting basin for every parameter [Formula: see text]. Further, regarding the set [Formula: see text] for [Formula: see text], we prove the following results: (1) There exists [Formula: see text] such that [Formula: see text]. (2) For every positive integer [Formula: see text], the set [Formula: see text] is non-empty. (3) For every prime number [Formula: see text], the set [Formula: see text] has at least two components. PMID- 27386300 TI - Seroprevalence of bovine brucellosis and associated risk factors in and around Alage district, Ethiopia. AB - Brucellosis is a zoonotic disease with economic and public health impact, particularly for human and animal populations within developing countries that relay on livestock production. A cross sectional study was conducted between October 2013 and March 2014 in and around Alage district to determine the seroprevalence of bovine brucellosis and associated risk factors. A total of 804 sera samples; 421 from cattle managed under extensive production system and 383 from cattle managed under intensive production system were collected. Multistage cluster sampling method was employed to sample unvaccinated cattle above 6 months of age. Rose Bengal Plate Test and c-ELISA were used in serial for detection of antibodies against Brucella species. The overall seroprevalence was 2.4 %, and herd level seroprevalence was 45.9 %. A prevalence of 3.3 and 1.3 % was recorded in the extensive and intensive farms respectively. Among the three sites, seropositivity of 3.4 % in Naka, 3.3 % in Negelewudisha and 1.3 % in Alage were recorded. Risk factors such as age, sex, number of service per conception, calving interval and reproductive status were associated with serostatus of brucellosis. Taken as a whole, cattle in both intensive and extensive production systems are endemically infected by brucellosis at low level in the study areas. This warrants the need of integrated intervention strategies to minimize the spread of the disease in animals and reduce the risk of transmission to humans. PMID- 27386301 TI - Age-dependent effects in the association between monetary delay discounting and risky sexual behavior. AB - BACKGROUND: Monetary delay discounting is a measure of impulsivity associated with substance use and abuse, problem gambling, and other health-related outcomes. More recently, delay discounting has been shown to be associated with risky sexual behavior. We analyzed survey data from men who have sex with men who completed a monetary discounting task and reported sexual behaviors in the previous 12 months. FINDINGS: Monetary delay discounting was associated with condomless anal intercourse among young (18-24 years), but not older, men who have sex with men. CONCLUSIONS: Monetary delay discounting may identify young men at increased risk of engaging in HIV risk behaviors. PMID- 27386302 TI - Common carotid artery diameter responds to intravenous volume expansion: an ultrasound observation. AB - BACKGROUND: In case of intravascular fluid depletion, large veins react to volume expansion with dilation. Little is known about the reaction of arterial vessels. We herein report on the effect of a standardized fluid bolus on the diameter of the common carotid artery (CCA) and its association with hemodynamic parameters, assessed in 20 mechanically ventilated patients after cardiac surgery. CCA was visualized using ultrasound, and the percentage increase in diastolic diameter was calculated by measuring before and after administration of crystalloid infusion solution. Invasive arterial blood pressure and pulse pressure variation (PPV) were assessed in parallel. RESULTS: Median diastolic CCA diameter was 6.2 (Q1-Q3: 5.4-7.1) mm, and it significantly increased to 6.7 (5.8-7.3) mm upon fluid administration [5.0 (1.9-10.5) % increase]. Mean arterial blood (MAP) pressure likewise increased from 68 (70-73) to 85 (71-100) mmHg, whereas PPV was significantly reduced from 17.6 (16.8-23.9) to 13.2 (6.7-18.1) %. There was a significant association between the change in CCA diameter and the hemodynamic response (delta-MAP: r = 0.53, delta-PPV: r = 0.56; p < 0.05). Furthermore, carotid diameter measured before volume expansion significantly correlated with the delta-PPV upon fluid administration (r = -0.5; p = 0.02). CONCLUSIONS: Diameter of the CCA increases in response to intravascular volume expansion. Additional studies on the interplay between carotid geometry and intravascular fluid status are necessary. PMID- 27386303 TI - Predictors of neonatal abstinence syndrome in buprenorphine exposed newborn: can cord blood buprenorphine metabolite levels help? AB - BACKGROUND: Buprenorphine is a semi-synthetic opioid used for the treatment of opioid dependence. Opioid use, including buprenorphine, has been increasing in recent years, in the general population and in pregnant women. Consequently, there has been a rise in frequency of neonatal abstinence syndrome (NAS), associated with buprenorphine use during pregnancy. The purpose of this study was to investigate correlations between buprenorphine and buprenorphine-metabolite concentrations in cord blood and onset of NAS in buprenorphine exposed newborns. METHODS: Nineteen (19) newborns who met inclusion criteria were followed after birth until discharge in a double-blind non-intervention study, after maternal consent. Cord blood and tissue samples were collected and analyzed by liquid chromatography-mass spectrometry (LC-MS) for buprenorphine and metabolites. Simple and multiple logistic regressions were used to examine relationships between buprenorphine and buprenorphine metabolite concentrations in cord blood and onset of NAS, need for morphine therapy, and length of stay. RESULTS: Each increase in 5 ng/ml level of norbuprenorphine in cord blood increases odds of requiring treatment by morphine 2.5 times. Each increase in 5 ng/ml of buprenorphine-glucuronide decreases odds of receiving morphine by 57.7 %. Along with concentration of buprenorphine metabolites, birth weight and gestational age also play important roles, but not maternal buprenorphine dose. CONCLUSIONS: LC MS analysis of cord blood concentrations of buprenorphine and metabolites is an effective way to examine drug and metabolite levels in the infant at birth. Cord blood concentrations of the active norbuprenorphine metabolite and the inactive buprenorphine-glucuronide metabolite show promise in predicting necessity of treatment of NAS. These finding have implications in improving patient care and reducing healthcare costs if confirmed in a larger sample. PMID- 27386304 TI - The possibility of coexistence and co-development in language competition: ecology-society computational model and simulation. AB - Language is characterized by both ecological properties and social properties, and competition is the basic form of language evolution. The rise and decline of one language is a result of competition between languages. Moreover, this rise and decline directly influences the diversity of human culture. Mathematics and computer modeling for language competition has been a popular topic in the fields of linguistics, mathematics, computer science, ecology, and other disciplines. Currently, there are several problems in the research on language competition modeling. First, comprehensive mathematical analysis is absent in most studies of language competition models. Next, most language competition models are based on the assumption that one language in the model is stronger than the other. These studies tend to ignore cases where there is a balance of power in the competition. The competition between two well-matched languages is more practical, because it can facilitate the co-development of two languages. A third issue with current studies is that many studies have an evolution result where the weaker language inevitably goes extinct. From the integrated point of view of ecology and sociology, this paper improves the Lotka-Volterra model and basic reaction-diffusion model to propose an "ecology-society" computational model for describing language competition. Furthermore, a strict and comprehensive mathematical analysis was made for the stability of the equilibria. Two languages in competition may be either well-matched or greatly different in strength, which was reflected in the experimental design. The results revealed that language coexistence, and even co-development, are likely to occur during language competition. PMID- 27386305 TI - Treatment of high-strength ethylene glycol waste water in an expanded granular sludge blanket reactor: use of PVA-gel beads as a biocarrier. AB - Industrial-scale use of polyvinyl alcohol (PVA)-gel beads as biocarriers is still not being implemented due to the lack of understanding regarding the optimal operational parameters. In this study, the parameters for organic loading rate (OLR), alkalinity, recycle rate, and addition of trace elements were investigated in an expanded granular sludge blanket reactor (EGSB) treating high-strength ethylene glycol wastewater (EG) with PVA-gel beads as biocarrier. Stable chemical oxygen demand (COD) removal efficiencies of 95 % or greater were achieved, and continuous treatment was demonstrated with appropriate parameters being an OLR of 15 kg COD/m(3)/day, NaHCO3 added at 400 mg/L, a recycle rate of 15 L/h, and no addition of trace elements addition. A biogas production yield rate of 0.24 m(3)/kg COD was achieved in this study. A large number of long rod-shaped bacteria (Methanosaeta), were found with low acetate concentration in the EGSB reactor. PMID- 27386306 TI - Assessment of technological level of stem cell research using principal component analysis. AB - BACKGROUND: In general, technological levels have been assessed based on specialist's opinion through the methods such as Delphi. But in such cases, results could be significantly biased per study design and individual expert. FINDINGS: In this study, therefore scientific literatures and patents were selected by means of analytic indexes for statistic approach and technical assessment of stem cell fields. The analytic indexes, numbers and impact indexes of scientific literatures and patents, were weighted based on principal component analysis, and then, were summated into the single value. Technological obsolescence was calculated through the cited half-life of patents issued by the United States Patents and Trademark Office and was reflected in technological level assessment. As results, ranks of each nation's in reference to the technology level were rated by the proposed method. Furthermore we were able to evaluate strengthens and weaknesses thereof. CONCLUSIONS: Although our empirical research presents faithful results, in the further study, there is a need to compare the existing methods and the suggested method. PMID- 27386307 TI - Adpositions and presuppositions. AB - This paper looks at presuppositions of adpositions, a topic which has not been examined much, in spite of the very large body of work on presuppositions. Some earlier assertions about adpositional presuppositions turn out not to be relevant, because (1) they are incorrect (2) presuppose and/or presupposition are not used in a technical sense in them, or (3) the presuppositions involved are not unique to adpositions. Some adpositions, e.g. despite, have been claimed to be factive, and thus could be presupposition triggers, but it is difficult to determine this, due to the fact that their complements are arguably always themselves presupposition triggers. On the other hand, directional adpositions are clearly presuppositional, as they trigger presuppositions about the location of an object/or entity before or after the motion whose description they are partly responsible for. Such facts may lead one to speculate about word classes and presuppositionality in general, and I will briefly discuss this issue. PMID- 27386308 TI - Trace metals health risk appraisal in fish species of Arabian Sea. AB - Fish is a vital food for humans and many animals. We report an environmental monitoring study to assess the trace metals in fish species caught from Arabian Sea and commercially available in the coastal city Karachi, Pakistan. Heavy metals such as copper, iron, lead and cadmium were determined in the skin, fillet and heart of the fish species Pampus argenteus, Epinephelus chlorostigma, Rachycentron canadum, Scomberomorus commerson, Johnius belangerii, Labeo rohita, Lutjanus argentimaculatus, Trachinotus blochii, Pomadsys olivaceum and Acanthopagrus berda by the atomic absorption spectrophotometer. The concentration (mg kg(-1), dry weight) range was: Cd (0.00-0.041), Cu (0.006-0.189), Fe (0.413 4.952) and Pb (0.00-0.569). Cadmium, copper and iron levels were below the tolerable limits whereas concentration of lead in the skins of S. commerson, E. chlorostigma, J. belangerii, A. berda; L. argentimaculatus, fillets of J. belangerii, E. chlorostigma and in the heart of J. belangerii exceeded the recommended limits. Therefore fish skin should be discouraged as food for humans or animals. The results indicate that a number of fish species have higher concentration of heavy metals dangerous for human health. Since the fish P. olivaceum (Dhotar) has the lowest level of trace metals therefore we recommend it for breeding and human consumption. PMID- 27386309 TI - A new generalization of Apostol type Hermite-Genocchi polynomials and its applications. AB - By using the modified Milne-Thomson's polynomial given in Araci et al. (Appl Math Inf Sci 8(6):2803-2808, 2014), we introduce a new concept of the Apostol Hermite Genocchi polynomials. We also perform a further investigation for aforementioned polynomial and derive some implicit summation formulae and general symmetric identities arising from different analytical means and generating functions method. The results obtained here are an extension of Hermite-Bernoulli polynomials (Pathan and Khan in Mediterr J Math 12:679-695, 2015a) and Hermite Euler polynomials (Pathan and Khan in Mediterr J Math 2015b, doi:10.1007/s00009 015-0551-1) to Apostol type Hermite-Genocchi polynomials defined in this paper. PMID- 27386310 TI - Process optimization for green synthesis of silver nanoparticles by Sclerotinia sclerotiorum MTCC 8785 and evaluation of its antibacterial properties. AB - BACKGROUND: Eco-friendly synthesis of nanoparticles is viewed as an alternative to the chemical method and initiated the use of microorganisms for synthesis. The present study has been designed to utilize plant pathogenic fungi Sclerotinia sclerotiorum MTCC 8785 strain for synthesis and optimization of silver nanoparticles (AgNPs) production as well as evaluation of antibacterial properties. The AgNPs were synthesized by reduction of aqueous silver nitrate (AgNO3) solution after incubation of 3-5 days at room temperature. The AgNPs were further characterized using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). Reaction parameters including media, fungal biomass, AgNO3 concentration, pH and temperature were further optimized for rapid AgNPs production. The antibacterial efficacy of AgNPs was evaluated against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 by disc diffusion and growth kinetics assay at the concentration determined by the minimum inhibitory concentration (MIC). RESULTS: AgNPs synthesis was initially marked by the change in colour from pale white to brown and was confirmed by UV-Vis spectroscopy. Optimization studies showed that potato dextrose broth (PDB) media, 10 g of biomass, addition of 2 mM AgNO3, pH 11 and 80 degrees C temperature resulted in enhanced AgNPs synthesis through extracellular route. TEM data revealed spherical shape AgNPs with size in the range of 10 nm. Presence of proteins capped to AgNPs was confirmed by FTIR. AgNPs showed antibacterial activity against E. coli and S. aureus at 100 ppm concentration, corresponding MIC value. CONCLUSION: S. sclerotiorum MTCC 8785 mediated AgNPs was synthesized rapidly under optimized conditions, which showed antibacterial activity. PMID- 27386312 TI - Measurement of neutron energy spectrum at the radial channel No. 4 of the Dalat reactor. AB - INTRODUCTION: Several compositions of neutron filters have been installed at the channel No. 4 of the Dalat research reactor to produce quasi-monoenergetic neutron beams. However, this neutron facility has been proposed to enhance the quality of the experimental instruments, and to characterize the neutron spectrum parameters for new filtered neutron beams of 2 keV, 24 keV, 59 keV and 133 keV. CASE DESCRIPTION: In order to meet the demand of neutron spectrum information for calculation and design of filtered neutron facilities at the Dalat nuclear research reactor (DNRR), the experimental determinations of neutron flux and energy spectrum, up to 8 MeV, has been performed at the inner entrance of the horizontal channel No. 4 from the core of DNRR. The Westcott neutron fluxes as well as the alpha-parameter that represents the deviation of epithermal neutron distribution from the 1/E law were measured by applying the cadmium ratio and the multi-foils activation methods. The fast neutron spectrum was measured based on the iterative adjustment procedure with threshold reactions. DISCUSSION AND EVALUATION: A set of pure metal thin foils with the diameter of 1.27 cm and thickness of 0.125 mm were used as threshold detectors to measure the integrated fluxes, and a calculation procedure on iterative adjustment was implemented to derive the differential neutron energy spectrum from the integrated values. CONCLUSIONS: The neutron fluxes and spectrum parameters were characterized with the measured values of 4.80 * 10(9), 1.98 * 10(7), 5.06 * 10(8) cm(-2) s(-1) and 0.0448 for the thermal, epithermal, fast neutron fluxes and the alpha-shape factor, respectively. The present result has been significantly applied to the input data for the Monte Carlo simulations in the developments of filtered mono energetic neutron beam facility at the institute. PMID- 27386311 TI - Habitual dietary protein intake affects body iron status in Japanese female college rhythmic gymnasts: a follow-up study. AB - BACKGROUND: Many rhythmic gymnasts stay lean by reducing their body weight (BW); however, this may result in iron deficiency (ID). Our previous cross-sectional study reported an association between ID incidence and protein intake in gymnasts during the pre-season. The present study aimed to examine the association between dietary protein intake and ID incidence in a 2-year follow-up study. METHODS: Elite Japanese female college rhythmic gymnasts [mean age +/- standard deviation (SD): 18.4 +/- 0.5 years] were recruited on a voluntary basis every August for 9 years. Anthropometric, dietary intake, and hematological parameters were measured at baseline and 2 years later. A total of 20 participants without ID at baseline were divided into either a lower (L, n = 11) or higher (H, n = 9) protein group based on median protein intake (1.3 g protein/kg BW). RESULTS: Participants consumed 1.08 +/- 0.16 and 1.55 +/- 0.14 g/kg BW of protein in the L and H groups, respectively. No significant changes in the intake of protein and other nutrients were observed between baseline and 2-year follow-up in both groups. ID was observed in a total of eight (72.8 %) participants in the L group and one (11.2 %) in the H group at follow-up. The incidence of ID was significantly lower in the H group than the L group (Fisher's exact test, odds ratio, 0.043; 95 % CI 0.004-0.552; p = 0.010). CONCLUSIONS: During the pre-season weight loss period, habitually higher protein intake may reduce ID incidence among elite college female rhythmic gymnasts. PMID- 27386313 TI - Uncovering the differences in linguistic network dynamics of book and social media texts. AB - Complex network studies span a large variety of applications including linguistic networks. To investigate the differences in book and social media texts in terms of linguistic typology, we constructed both sequential and sentence collocation networks of book, Facebook and Twitter texts with undirected and weighted edges. The comparisons are performed using the basic parameters like average degree, modularity, average clustering coefficient, average path length, diameter, average link weight etc. We also presented the distribution graphs for node degrees, edge weights and maximum degree differences of the pairing nodes. The degree difference occurrences are furtherly detailed with the grayscale percentile plots with respect to the edge weights. We linked the network analysis with linguistic aspects like word and sentence length distributions. We concluded that linguistic typology demonstrates a formal usage in book that slightly deviates to informal in Twitter. Facebook interpolates between these media by the means of network parameters, while the informality of Twitter is mostly influenced by the character limitations. PMID- 27386314 TI - A new Sumudu transform iterative method for time-fractional Cauchy reaction diffusion equation. AB - In this paper, a new Sumudu transform iterative method is established and successfully applied to find the approximate analytical solutions for time fractional Cauchy reaction-diffusion equations. The approach is easy to implement and understand. The numerical results show that the proposed method is very simple and efficient. PMID- 27386315 TI - Experimental studies on the effects of bolt parameters on the bearing characteristics of reinforced rock. AB - Roadways supported by bolts contain support structures that are built into the rock surrounding the roadway, referred to as reinforced rocks in this paper. Using physical model simulation, the paper investigates the bearing characteristics of the reinforced rock under different bolt parameters with incrementally increased load. The experimental results show that the stress at the measurement point inside the structure varies with the kinetic pressure. The stress increases slowly as the load is initially applied, displays accelerated growth in the middle of the loading application, and decreases or remains constant in the later stage of the loading application. The change in displacement of the surrounding rock exhibits the following characteristics: a slow increase when the load is first applied, accelerated growth in the middle stage, and violent growth in the later stage. There is a good correlation between the change in the measured stress and the change in the surrounding rock displacement. Increasing the density of the bolt support and the length and diameter of the bolt improves the load-bearing performance of the reinforced rock, including its strength, internal peak stress, and residual stress. Bolting improves the internal structure of the surrounding rocks, and the deterioration of the surrounding rock decreases with the distance between the bolt supports. PMID- 27386316 TI - A quantum chemical study of the mechanisms of olefin addition to group 9 transition metal dioxo compounds. AB - The mechanistic aspects of ethylene addition to MO2(CH2)(CH3) (M=Co, Rh, Ir) have been investigated with a Hartree-Fock/DFT hybrid functional at the MO6/LACVP* and B3LYP/LACVP* levels of theory to elucidate the reaction pathways on the singlet, doublet and triplet potential energy surfaces (PES). In the reaction of the IrO2CH2CH3 complex with ethylene, [3 + 2]C,O addition is the most plausible pathway on the singlet PES, the [3 + 2]O,O addition is the most favoured pathway on the doublet surface whiles the stepwise [1 + 1] addition involving the oxygen atom of the complex in the first step and the carbon atom of the complex in the second step is the most plausible pathway on the triplet PES. For the reaction of the RhO2(CH2)(CH3) complex, the [2 + 2]Rh,O addition pathway is the most favoured on the singlet surface, the [2 + 2]Rh,C is the most plausible pathway on the triplet PES and [3 + 2]C,O is the most plausible on the doublet surface. For the reactions of the CoO2(CH2)(CH3) complex, the [1 + 2]O addition is the most plausible on the singlet PES, [3 + 2]C=Co=O cycloaddition to form the five membered intermediate is the most preferred pathway on the doublet PES, whiles on the triplet PES the preferred pathway is the [3 + 2] addition across the O=Co=O bond of the metal complex. The reactions of olefins with the Co dioxo complex have lower activation barriers for the preferred [3 + 2] and [2 + 2] addition pathways as well as fewer side reactions than those of the rhodium and iridium systems. This could imply that the cobalt dioxo complexes can efficiently and selectively catalyze specific reactions in oxidation of olefins than Rh and Ir oxo complexes will do and therefore Co oxo complexes may be better catalysts for specific oxidation reactions of olefins than Rh and Ir complexes are. The activation barriers for the formation of the four-or five-membered metallacycle intermediates through [2 + 2] or [3 + 2] cyclo-addition are lower on the triplet PES than on the singlet PES for the formation of similar analogues. There are fewer competitive reaction pathways on the triplet surface than on the singlet PES. Also, cycloadditions that seem impossible on the singlet PES seem possible on the doublet and or triplet PESs, this is the case typically for the Rh and Co complexes, illustrating the importance of multiple spin states in organometallic reactions.Graphical AbstractTable of Contents Synopsis: A study of the mechanism of ethylene addition to MO2(CH2)(CH3)(M=Co,Rh,Ir) shows the reactions of the Co complex have lower activation barriers for the preferred [3+2] and [2+2] addition pathways and fewer side reactions than those of Rh and Ir. Reactions are more feasible and selective on the triplet PES than on the singlet PES. These illustrate the importance of multiple spin states in organometallic reactions and shows catalyst activity and selectivity decreases down the group. PMID- 27386317 TI - An intermediate significant bit (ISB) watermarking technique using neural networks. AB - Prior research studies have shown that the peak signal to noise ratio (PSNR) is the most frequent watermarked image quality metric that is used for determining the levels of strength and weakness of watermarking algorithms. Conversely, normalised cross correlation (NCC) is the most common metric used after attacks were applied to a watermarked image to verify the strength of the algorithm used. Many researchers have used these approaches to evaluate their algorithms. These strategies have been used for a long time, however, which unfortunately limits the value of PSNR and NCC in reflecting the strength and weakness of the watermarking algorithms. This paper considers this issue to determine the threshold values of these two parameters in reflecting the amount of strength and weakness of the watermarking algorithms. We used our novel watermarking technique for embedding four watermarks in intermediate significant bits (ISB) of six image files one-by-one through replacing the image pixels with new pixels and, at the same time, keeping the new pixels very close to the original pixels. This approach gains an improved robustness based on the PSNR and NCC values that were gathered. A neural network model was built that uses the image quality metrics (PSNR and NCC) values obtained from the watermarking of six grey-scale images that use ISB as the desired output and that are trained for each watermarked image's PSNR and NCC. The neural network predicts the watermarked image's PSNR together with NCC after the attacks when a portion of the output of the same or different types of image quality metrics (PSNR and NCC) are obtained. The results indicate that the NCC metric fluctuates before the PSNR values deteriorate. PMID- 27386318 TI - Assessment of organochlorine pesticide residues in soils and drinking water sources from cocoa farms in Ghana. AB - Residues of organochlorine pesticides were determined in soils and drinking water sources in cocoa growing areas in Ghana. Soil samples analysed showed the presence of four organochlorine pesticide residues namely lindane (0.005-0.05 mg/kg), beta-HCH (<0.01-0.05 mg/kg), dieldrin (0.005-0.02 mg/kg), and p,p'-DDT (0.005-0.04 mg/kg), with dieldrin occurring most frequently. Similarly, organochlorine pesticide residues detected in the water samples were lindane (0.01-0.03 ug/l), alpha-endosulfan (0.01-0.03 ug/l), endosulfan-sulphate (0.01 0.04 ug/l), dieldrin (0.01-0.03 ug/l) and p,p'-DDT (0.01-0.04 ug/l), with heptachlor occurring most frequently. The concentrations of the detected organochlorine residues in the soil samples were below their respective US maximum residues limits (MRLs) for agricultural soils, except for lindane recorded at Kwakuanya (S4) and beta-HCH recorded at Krakrom (S3) and Kwakuanya (S4). Similarly, the organochlorine pesticide residues recorded in the water samples were below and within their respective WHO MRLs for drinking water except for alpha-endosulfan at Diabaa (S2) and Kwakuanya (S4) at distance 0-15 m and Kwakuanya (S4) at distance 16-30 m, endosulfan-sulfate at Nkrankwanta (S1) and Diabaa (S2) at distance 0-15 m and heptachlor at Krakrom (S3) at distance 16-30 m which were above their WHO MRLs. The presence of the banned organochlorine pesticide residues in soil and water samples from the study area indicates that these chemicals are still being used, illegally, on some cocoa farms. Routine monitoring of pesticide residues in the study area is necessary for the prevention, control and reduction of environmental pollution to minimize health risks. PMID- 27386319 TI - Survey of coccidial infection of rabbits in Sichuan Province, Southwest China. AB - Coccidiosis is a challenging disease of wild and domestic rabbits both, caused by Eimeria and thereby leads enormous economic losses at rabbit farms. The present study carried out to survey the prevalence and intensity of coccidial infection among the rabbits in Sichuan Province, southwest China. A total of 110 faecal samples were collected from 11 farms situated in eight main rabbits rearing administrative regions. Oocysts in faecal samples were purified, sporulated and identified according to morphological features. The overall prevalence of infection was 56.4 % (62/110), with prevalence of 64 % (47/75) for local meat breeds of rabbit and 51.4 % (18/35) for Rex Rabbits (local fur rabbits). Weanling rabbits had the highest prevalence (74 %, 37/50), followed by young rabbits (45 %, 13/29) and the adult rabbits showed the lowest prevalence (42 %, 13/31). Concurrent infection with two to seven Eimeria species was found. In total, 9 species of Eimeria were identified from oocyst-positive samples. E. perforans was the most prevalent specie (42.73 %), followed in order by Eimiera media, E. irresidua, E. magna, and E. intestinalis with prevalences of 35.45, 34.55, 31.82, and 23.64 %, respectively. Results of the present investigation indicated that the prevalence of coccidial infection is high among the rabbit population in southwest China. This study also elucidate about the coccidial infection and emphasis to adopt control strategies in commercial rabbitories. PMID- 27386321 TI - On the pth moment estimates of solutions to stochastic functional differential equations in the G-framework. AB - The aim of the current paper is to present the path-wise and moment estimates for solutions to stochastic functional differential equations with non-linear growth condition in the framework of G-expectation and G-Brownian motion. Under the nonlinear growth condition, the pth moment estimates for solutions to SFDEs driven by G-Brownian motion are proved. The properties of G-expectations, Holder's inequality, Bihari's inequality, Gronwall's inequality and Burkholder Davis-Gundy inequalities are used to develop the above mentioned theory. In addition, the path-wise asymptotic estimates and continuity of pth moment for the solutions to SFDEs in the G-framework, with non-linear growth condition are shown. PMID- 27386320 TI - The support of medication reviews in hospitalised patients using a clinical decision support system. AB - OBJECTIVES: First, to estimate the added value of a clinical decision support system (CDSS) in the performance of medication reviews in hospitalised elderly. Second, to identify the limitations of the current CDSS by analysing generated drug-related problems (DRPs). METHODS: Medication reviews were performed in patients admitted to the geriatric ward of the Zuyderland medical centre. Additionally, electronically available patient information was introduced into a CDSS. The DRP notifications generated by the CDSS were compared with those found in the medication review. The DRP notifications were analysed to learn how to improve the CDSS. RESULTS: A total of 223 DRP strategies were identified during the medication reviews. The CDSS generated 70 clinically relevant DRP notifications. Of these DRP notifications, 63 % (44) were also found during the medication reviews. The CDSS generated 10 % (26) new DRP notifications and conveyed 28 % (70) of all 249 clinically relevant DRPs that were found. Classification of the CDSS generated DRP notifications related to 'medication error type' revealed that 'contraindications/interactions/side effects' and 'indication without medication' were the main categories not identified during the manual medication review. The error types 'medication without indication', 'double medication', and 'wrong medication' were mostly not identified by the CDSS. CONCLUSIONS: The CDSS used in this study is not yet sufficiently advanced to replace the manual medication review, though it does add value to the manual medication review. The strengths and weaknesses of the current CDSS can be determined according to the medication error types. PMID- 27386322 TI - A double-hurdle model estimation of cocoa farmers' willingness to pay for crop insurance in Ghana. AB - Agriculture is an important sector in Ghana's economy, however, with high risk due to natural factors like climate change, pests and diseases and bush fires among others. Farmers in the Brong-Ahafo region of Ghana which is known as one of the major cocoa producing regions, face these risks which sometimes results in crop failure. The need for farmers to therefore insure their farms against crop loss is crucial. Insurance has been a measure to guard against risk. The aim of this study was to assess cocoa farmers' willingness to access crop insurance, the factors affecting willingness to pay (WTP) for crop insurance scheme and insurance companies' willingness to provide crop insurance to cocoa farmers. Multi-stage sampling technique was used to sample 240 farmers from four communities in the Dormaa West District in Brong-Ahafo Region. The double-hurdle model shows that age, marital status and education significantly and positively influenced cocoa farmer's willingness to insure their farms whiles household size and cropped area negatively influenced farmers' willingness to insure their farms. Similarly, age, household size and cropped area significantly and positively influenced the premium cocoa farmers were willing to pay whiles marital status and cocoa income negatively influenced the premium farmers were willing to pay. The contingent valuation method shows that the maximum, minimum and average amounts cocoa farmers are willing to pay for crop insurance per production cost per acre was GHc128.40, GHc32.10 and GHc49.32 respectively. Insurance companies do not have crop insurance policy but willing to provide crop insurance policy to cocoa farmers on a condition that farmers adopt modern cultivation practices to reduce the level of risk. The study recommends that cocoa farmers should be well educated on crop insurance and should be involved in planning the crop insurance scheme in order to conclude on the premium to be paid by them. PMID- 27386323 TI - Cytogenetic analysis of spontaneously discharged products of conception by array based comparative genomic hybridization. AB - BACKGROUND: Cytogenetic analysis of products of conception (POC) is essential for the management of recurrent pregnancy loss (RPL), but the currently-performed G banding method is not necessarily applicable to spontaneously discharged POC because of poor quality for culture. We analyzed the karyotypes of 15 spontaneously discharged POC by array-based comparative genomic hybridization (array-CGH). RESULTS: All specimens were successfully analyzed and 10 cases had abnormal results: gain in copy number (n = 7) and loss in copy number (n = 3). Most of them were estimated to be whole chromosome aneuploidy, whereas one case was compatible with microdeletion. Two cases were suspected to be male diploid contaminated by maternal DNA or triploid because of the unsatisfactory signal patterns on X/Y chromosomes. Two of three cases with normal female DNA pattern were identified to be contaminated with maternal DNA by the additional analysis of short tandem repeats. CONCLUSIONS: Given the potential to analyze non-viable POC specimens, array-CGH is a feasible cytogenetic tool for women, in particular, with a history of RPL who desire non-surgical or expectant management of miscarriages and/or a thorough investigation on the cause for recurrent miscarriage, although it needs to take into account high incidence of maternal contamination in spontaneously discharged POC. PMID- 27386324 TI - Schizophrenia-like psychosis and gitelman syndrome: a case report and literature review. AB - INTRODUCTION: Gitelman syndrome(GS) is a rare inherited tubular disorder which is characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria. Here, we report a case of schizophrenia-like psychosis concomitant with GS and related literatures are reviewed. CASE DESCRIPTION: An 18-year-old male patient with 1-week history of auditory hallucinations, sense of insecurity, delusions of reference and feelings of being followed and controlled by others unknown, insomnia was admitted to Psychiatry department in December, 2013. Hypokalemia and hypomagnesemia were noted. He was diagnosed as schizophrenia-like psychosis. Treatment with paliperidone at the dose of 6 mg/day and magnesium and potassium supplementations was commenced. However, electrolyte disturbances failed to improve following psychosis remission. Therefore, other underlying diseases resulting in electrolyte disturbances were suspected. Along with hypokalemia and hypomagnesemia, additional investigation showing metabolic alkalosis, hypocalciuria, renal loss of potassium, were consistent with GS. Gene analysis revealed this patient carried out c. 2687 G > A homozygous mutation of exon 23 in the SLC12A3 gene which led to p.Arg896Gln. Eventually, GS was identified. Thus, additional spironolactone (40 mg/day) combined with increased doses of oral potassium chloride sustained-release tablets (3.0 g/day) and potassium magnesium aspartate (0.3 g/day) were administered. During next half a year, fatigue resolved, paliperidone gradually tapered and eventually discontinued while psychosis maintained complete remission. His serum potassium was near normal (3.2-3.5 mmol/L), hypomagnesemia significantly improved (0.57 0.67 mmol/L). DISCUSSION AND EVALUATION: Electrolyte abnormalities secondary to GS might cause or contribute to development of neuropsychiatric symptoms. In turn, hypokalemia was common among acute psychiatric inpatients. As a consequence, when concomitant with psychosis, GS was readily concealed. CONCLUSION: Electrolyte disturbances are common in acute psychiatric patients. However, when electrolyte disturbances are not improved following psychosis remission, other underlying diseases such as GS should be considered. PMID- 27386325 TI - Fine needle aspiration cytology guided by ultrasound in the diagnosis of subcentimetre thyroid nodules. AB - BACKGROUND: This study aimed to investigate the value of fine needle aspiration biopsy (FNAB) under ultrasound guidance in diagnosis of thyroid nodules. In a retrospective analysis of FNAB in 1050 cases of patients with 1100 nodules, patients were divided according to the maximum diameter of their nodules into two groups: >1.0 and <=1.0 cm. The ultrasound-guided FNAB cytology results were compared between two groups. RESULTS: Ultrasound findings showed that among 1100 thyroid nodules, 547 were highly suspicious, 358 were moderately, 175 were low, and 19 were very low. Cytology results showed papillary carcinomas in 453, possible papillary cancer in 126 cases, follicular tumors in 26, suspicious follicular tumors in 6, atypical cells in 7, nodular goiter in 289, colloid in 13, chronic lymphocytic thyroiditis in 175, and undiagnosed specimen in 5. Ultrasound diagnosis of thyroid nodules had an overall sensitivity of 86.0 %, and a specificity of 81.9 %. In nodules larger than 1.0 cm, the sensitivity was 92.8 %, and the specificity 92.3 %. In nodules <=1.0 cm, the sensitivity was 82.4 %, and the specificity was 81.7 %. CONCLUSIONS: Patients with highly suspicious thyroid nodules on ultrasonography, regardless of nodule sizes, should receive ultrasound-guided FNAB to confirm their natures and direct clinical managements. PMID- 27386326 TI - Elevated C-reactive protein is associated with disease progression in patients with mild Crohn's disease. AB - BACKGROUND: Few studies have been conducted on the progression of mild Crohn's disease (CD). We aimed to investigate the natural course in mild CD patients with or without bowel damage, to identify predictors of bowel resection and to calculate the requirement for rescue medication. METHODS: A total of 104 patients with mild activity (150 < CDAI < 220) with or without bowel damage were identified from among 1050 CD patients between January 2008 and May 2014. Univariate and multivariate analysis was used to identify factors associated with bowel resection. The cumulative probabilities of bowel resection and rescue medication such as steroids or anti-TNF agents were calculated. RESULTS: The median follow-up duration was 28.2 months (IQR 26.7). Cumulative probabilities of bowel resection were 0.2, 11.8 and 42.4 % at 1, 3 and 5 years respectively. The CD patients with bowel damage had a higher bowel resection rate than those without bowel damage (P < 0.001). The cumulative probabilities of corticosteroid requirement were 3.0, 19.6 and 78.4 % of patients at 1, 3 and 5 years, respectively, and 2.1, 11.9 and 56.1 %, in terms of the cumulative probabilities of requiring anti-TNF agents. Patients with elevated CRP (>1.6 mg/dL) were more likely to undergo bowel resection (P = 0.032). CONCLUSIONS: Even in CD patients with mild disease activity, the cumulative probability of bowel resection is not low if they have bowel damage or elevated CRP at baseline. Mild CD patients with bowel damage or elevated CRP at baseline need special attention. PMID- 27386328 TI - The aesthetic values of silence and its impacts on romanticism and contemporary artists. AB - In our modern world, where people suffer from self-alienation and are after the meaning of existence in their mechanical and flamboyant outside world, finding a discernible language is very important. People's dejected minds are the products of miserable modern societies that have changed them into taciturn and uncommunicative creatures in search of meaning. The significance of language, specifically poetic or living language, is undeniable in different eras. Therefore, it would be easier for artists to communicate with people by letting them get the maximum meaning with the least amount of words. This is something that happens in the discourse of modern people. This article shows the aesthetic values of silence and its impacts on romantic and contemporary artists, who for us here will be represented by Samuel Taylor Coleridge as a romantic artist versus Harold Pinter as a contemporary dramatist. PMID- 27386327 TI - Re-irradiation of recurrent pediatric ependymoma: modalities and outcomes: a twenty-year survey. AB - BACKGROUND: Standard treatment for recurrent ependymomas is not defined. Re- irradiation has been proposed but its modalities and results are still to be explored. PATIENTS AND METHODS: From June 1994 to December 2013, 32 pediatric patients with ependymoma were re-irradiated for local (n = 15) or metastatic (n = 17) relapses. Files were reviewed retrospectively. RESULTS: Local relapses were treated with hypofractionated focal radiotherapy (hypoFFRT) (n = 8) or focal fractionated radiotherapy (FFRT) (n = 7). Metastatic relapses were treated with hypoFFRT (n = 3), FFRT (n = 3), spinal radiotherapy (n = 4) and craniospinal irradiation (CSI) (n = 7). Median PFS and OS after re-irradiation were 1.2 and 3.5 years respectively with a median follow-up of 2.1 years (0.2-11.4). For local relapses, median PFS was 2.5 years for patients treated with hypoFFRT versus 1.2 years for patients treated with FFRT (p = 0.2). For metastatic relapses, median PFS was 0.7 years for patients treated with focal radiotherapy (hypoFFRT, FFRT, spinal radiotherapy) versus 6.8 years for patients treated with CSI (p = 0.073). 15 patients achieved greater PFS after second radiotherapy (RT2) than after first radiotherapy (RT1). 27 patients (84 %) had surgery before re-irradiation. PFS was better for patients with GTR before RT2 (14.7 vs 6.7 months) (p = 0.05). 5 patients developed radionecrosis; only one required corticosteroids. CONCLUSION: Re-irradiation at relapse is a safe, feasible and potentially curative treatment. Metastatic relapse may require CSI even when isolated and re-operated. For local relapses, considering conflicting results in the literature, a randomized trial is warranted to explore fractionated focal radiotherapy versus hypofractionated focal irradiation. PMID- 27386329 TI - New hybrid conjugate gradient methods with the generalized Wolfe line search. AB - The conjugate gradient method was an efficient technique for solving the unconstrained optimization problem. In this paper, we made a linear combination with parameters beta k of the DY method and the HS method, and putted forward the hybrid method of DY and HS. We also proposed the hybrid of FR and PRP by the same mean. Additionally, to present the two hybrid methods, we promoted the Wolfe line search respectively to compute the step size alpha k of the two hybrid methods. With the new Wolfe line search, the two hybrid methods had descent property and global convergence property of the two hybrid methods that can also be proved. PMID- 27386330 TI - On two fractional differential inclusions. AB - We investigate in this manuscript the existence of solution for two fractional differential inclusions. At first we discuss the existence of solution of a class of fractional hybrid differential inclusions. To illustrate our results we present an illustrative example. We study the existence and dimension of the solution set for some fractional differential inclusions. PMID- 27386331 TI - Compact filtering monopole patch antenna with dual-band rejection. AB - In this paper, a compact ultra-wideband patch antenna with dual-band rejection is proposed. The proposed antenna filters 3.3-3.8 GHz WiMAX and 5.15-5.85 GHz WLAN by respectively rejecting these bands through a C-shaped slit and a lambdag/4 resonator. The lambdag/4 resonator is positioned as a pair, centered around the microstrip line, and a C-type slit is inserted into an elliptical patch. The impedance bandwidth of the proposed antenna is 2.9-9.3 GHz, which satisfies the bandwidth for ultra-wideband communication systems. Further, the proposed antenna provides dual-band rejection at two bands: 3.2-3.85 and 4.7-6.03 GHz. The radiation pattern of the antenna is omnidirectional, and antenna gain is maintained constantly while showing -8.4 and -1.5 dBi at the two rejected bands, respectively. PMID- 27386332 TI - Electrical muscle stimulation in thomboprophylaxis: review and a derived hypothesis about thrombogenesis-the 4th factor. AB - INTRODUCTION: Electrical muscle stimulation (EMS) is an FDA-approved thromboprophylactic method. Thrombus pathogenesis is considered to depend on factors related to components of the vessel wall, the velocity of blood, and blood consistency-collectively known as, the Virchow's triad. OBJECTIVE: The testimony supporting the thromboprophylactic effects of the EMS is reviewed. An emphasis is placed on the fact that, EMS has demonstrated, in certain circumstances, an efficacy rate that cannot be fully explained by the Virchow's triad; also that, in reviewing relevant evidence and the theorized pathophysiological mechanisms, several findings collectively point to a potentially missed point. Remarkably, venous thromboembolic disease (VTE) is extremely more common in the lower versus the upper extremities even when the blood velocities equalize; EMS had synergistic effects with intermittent compressive devices, despite their presumed identical mechanism of action; sleep is not thrombogenic; non-peroperative EMS is meaningful only if applied >=5 times daily; neural insult increases VTEs more than the degree expected by the hypomobility-related blood stasis; etc. These phenomena infer the presence of a 4th thrombogenetic factor: neural supply to the veins provides direct antithrombic effects, by inducing periodic vessel diameter changes and/or by neuro-humoral, chemically acting factors. EMS may stimulate or substitute the 4th factor. This evidence-based hypothesis is analyzed. CONCLUSION: A novel pathophysiologic mechanism of thrombogenesis is supported; and, based on this, the role of EMS in thromboprophylaxis is expanded. Exploration of this mechanism may provide new targets for intervention. PMID- 27386333 TI - Heavy metal exposure, in combination with physical activity and aging, is related with oxidative stress in Japanese women from a rural agricultural community. AB - This study aimed to evaluate the relationships between oxidative stress and heavy metal exposure (lead [Pb] and cadmium [Cd]), as well as co-factors such as physical activity and age, in Japanese women. This study was conducted with female subjects from a rural agricultural community in Japan. Subjects were asked to complete lifestyle-related questionnaires and undergo a group health examination. Physical activity, alcohol consumption, body mass index, and other demographic information were collected. Blood and urine samples were collected to measure urinary 8-hydroxydeoxyguanosine (8-OHdG) levels and blood and urinary Cd and Pb concentrations. Urine samples were analyzed using high performance liquid chromatography and flameless atomic absorption spectrometry; blood samples were analyzed using inductively coupled plasma-mass spectrometry. Age, physical activity, and blood and urinary Cd and Pb concentrations were included in structural equation modeling analysis. Two latent factors for heavy metal exposure and physical activity were produced to predict the total influence of the variables. The final model was good: CMIN/DF = 0.775, CFI = 1.000, GFI = 0.975, AGFI = 0.954, RMSEA = 0.000. 8-OHdG levels were positively associated with heavy metal exposure, physical activity, and age (standard beta of path analysis: 0.33, 0.38, and 0.20, respectively). Therefore, oxidative stress is associated with both, environmental and lifestyle factors, in combination with aging. PMID- 27386334 TI - HIV-1 diversity in infected individuals in Suzhou and Suqian, China. AB - Jiangsu is one province with severe HIV-1 epidemic in China. However, the molecular epidemiological characterizations of HIV-1 in many cities of Jiangsu remain unclear. A molecular epidemiological investigation was performed based on 38 HIV-positive samples collected from Suzhou and Suqian during 2011-2013. Five HIV-1 genomic fragments, p17, pol, vif-vpr, vpr-env, and C2V3 were amplified and sequenced from these samples. HIV-1 group M subtype of each sample was determined by phylogenetic analyses with the standard reference sequences. Among these infected individuals, 81.6 % (31/38) self-reported to be infected via sexual contacts, including 50.0 % (19/38) via heterosexual contact and 31.6 % (12/38) via homosexual contact. Among 34 samples with available pol or vif-env sequence, 19 (55.9 %) CRF01_AE, 7 (20.6 %) CRF07_BC, 3 (8.8 %) CRF08_BC, and 5 (14.7 %) inter-subtype recombinants were identified. No pure B, B' and C subtypes were found in this cohort. The five recombinants contain one B/C, three CRF01/B and one CRF01/B/C recombinants. These results suggest that CRF01_AE was the most predominant HIV-1 group M subtype and CRF01_AE-involved recombinants were the major recombinant forms. Comparison showed that there was no obvious difference in HIV-1 group M subtype distribution between Jiangsu (including Suzhou and Suqian) and the surrounding provinces (e.g., Shanghai, Anhui, and Shandong). CRF01_AE and CRF07_BC were the top two predominant HIV-1 genotypes in Jiangsu, and less and/or no pure subtype B and C was currently circulating here. We predicted that more CRF01/CRF07 recombinants, but fewer B/C recombinants will be generated in Jiangsu in future. PMID- 27386335 TI - Ammonium chloride catalyzed synthesis of novel Schiff bases from spiro[indoline 3,4'-pyran]-3'-carbonitriles and evaluation of their antimicrobial and anti breast cancer activities. AB - BACKGROUND: Indolinone and spiro-indoline derivatives have been employed in the preparation of different important therapeutic compounds required for treatment of anticonvulsants, antibacterial, Antitubercular, and anticancer activities. Schiff bases have been found to possess various pharmacological activities such as antitubercular, plant growth inhibiting, insecticsidal, central nerve system depressant, antibacterial, anticancer, anti-inflammatory, and antimicrobial. Mannich bases have a variety of biological activities such as antibacterial and antifungal activities. RESULTS: In this study, a green, rapid and efficient protocol for the synthesis of a new series of Schiff bases from spiro[indoline 3,4'-pyran]-3'-carbonitrile derivatives using ammonium chloride as a very inexpensive and readily available reagent. The prepared compounds were assessed in vitro for their antimicrobial activity. Also, the cytotoxic activity of the prepared compounds was assessed in vitro against human cells line MCF7 breast cancer. CONCLUSION: Good activity was distinguished for Schiff bases from spiro[indoline-3,4'-pyran]-3'-carbonitriles, with some members recorded higher antimicrobial and anti-breast cancer activities.Graphical abstractNovel Schiff bases from spiro[indoline-3,4'-pyran]-3'-carbonitriles. PMID- 27386337 TI - Development of a qualitative real-time PCR method to detect 19 targets for identification of genetically modified organisms. AB - As the amount of commercially available genetically modified organisms (GMOs) grows recent years, the diversity of target sequences for molecular detection techniques are eagerly needed. Considered as the gold standard for GMO analysis, the real-time PCR technology was optimized to produce a high-throughput GMO screening method. With this method we can detect 19 transgenic targets. The specificity of the assays was demonstrated to be 100 % by the specific amplification of DNA derived from reference material from 20 genetically modified crops and 4 non modified crops. Furthermore, most assays showed a very sensitive detection, reaching the limit of ten copies. The 19 assays are the most frequently used genetic elements present in GM crops and theoretically enable the screening of the known GMO described in Chinese markets. Easy to use, fast and cost efficient, this method approach fits the purpose of GMO testing laboratories. PMID- 27386336 TI - Effects of dietary lysine levels on plasma free amino acid profile in late-stage finishing pigs. AB - Muscle growth requires a constant supply of amino acids (AAs) from the blood. Therefore, plasma AA profile is a critical factor for maximizing the growth performance of animals, including pigs. This research was conducted to study how dietary lysine intake affects plasma AA profile in pigs at the late production stage. Eighteen crossbred (Large White * Landrace) finishing pigs (nine barrows and nine gilts; initial BW 92.3 +/- 6.9 kg) were individually penned in an environment controlled barn. Pigs were assigned randomly to one of the three dietary treatments according to a randomized complete block design with sex as block and pig as experiment unit (6 pigs/treatment). Three corn- and soybean meal based diets contained 0.43 % (lysine-deficient, Diet I), 0.71 % (lysine-adequate, Diet II), and 0.98 % (lysine-excess, Diet III) l-lysine, respectively. After a 4 week period of feeding, jugular vein blood samples were collected from the pigs and plasma was obtained for AA analysis using established HPLC methods. The change of plasma lysine concentration followed the same pattern as that of dietary lysine supply. The plasma concentrations of threonine, histidine, phenylalanine, isoleucine, valine, arginine, and citrulline of pigs fed Diet II or III were lower (P < 0.05) than that of pigs fed Diet I. The plasma concentrations of alanine, glutamate, and glycine of pigs fed Diet II or III were higher (P < 0.05) than that of pigs fed Diet I. The change of plasma leucine and asparagine concentrations followed the patterns similar to that of plasma lysine. Among those affected AAs, arginine was decreased (P < 0.05) in the greatest proportion with the lysine-excess diet. We suggest that the skeletal muscle growth of finishing pigs may be further increased with a lysine-excess diet if the plasma concentration of arginine can be increased through dietary supplementation or other practical nutritional management strategies. PMID- 27386338 TI - Speed-up hyperspheres homotopic path tracking algorithm for PWL circuits simulations. AB - In the present work, we introduce an improved version of the hyperspheres path tracking method adapted for piecewise linear (PWL) circuits. This enhanced version takes advantage of the PWL characteristics from the homotopic curve, achieving faster path tracking and improving the performance of the homotopy continuation method (HCM). Faster computing time allows the study of complex circuits with higher complexity; the proposed method also decrease, significantly, the probability of having a diverging problem when using the Newton-Raphson method because it is applied just twice per linear region on the homotopic path. Equilibrium equations of the studied circuits are obtained applying the modified nodal analysis; this method allows to propose an algorithm for nonlinear circuit analysis. Besides, a starting point criteria is proposed to obtain better performance of the HCM and a technique for avoiding the reversion phenomenon is also proposed. To prove the efficiency of the path tracking method, several cases study with bipolar (BJT) and CMOS transistors are provided. Simulation results show that the proposed approach can be up to twelve times faster than the original path tracking method and also helps to avoid several reversion cases that appears when original hyperspheres path tracking scheme was employed. PMID- 27386339 TI - Analytical multi-soliton solutions of a (2+1)-dimensional breaking soliton equation. AB - The analytical solutions for a (2+1)-dimensional breaking solution equation is proposed in this paper by using mapping and projective method darboux transformation, and Some exact propagating solutions are constructed for this Breaking equation, and the M * N multi-soliton could be obtained by using Weierstrassp function and setting the perfect parameters. The potential application of breaking Soliton equation will be of great interest in future research. PMID- 27386340 TI - Clinical profile of tetanus patients attended at Felege Hiwot Referral Hospital, Northwest Ethiopia: a retrospective cross sectional study. AB - BACKGROUND: Tetanus is an acute, often fatal, disease caused by an exotoxin produced by the bacterium Clostridium tetani. It is characterized by generalized rigidity and convulsive spasms of skeletal muscles. Tetanus remains a major public health problem in Ethiopia like other developed nations. The aim of the present study was to assess the clinical profile and outcome of tetanus patients in a referral hospital, Northwest Ethiopia. METHODS: This is a retrospective cross sectional study in which we collected, compiled and analyzed medical records of patients aged greater than 15 years who were admitted at Felege Hiwot Referral Hospital from Sep 2012 to Sep 2015. Tetanus was diagnosed using clinical observations. Data were entered, cleared, and analyzed using SPSS statistical software package. RESULTS: Among 110 tetanus cases 84 (76.4 %) were males. Trauma was the most common antecedent cause. Most of the patients had no history of tetanus toxoid immunization. Aspiration pneumonia at 34.5 % and dysautonomia at 11.8 % were found to be the most frequently observed complications. About 36 (32.7 %) patients were died due to tetanus and the most common immediate cause of death was respiratory failure at (83.3 %). Patients' area of residence (p = 0.004), type of complications (p = 0.00) and severity of tetanus (p = 0.00) were found to be statistically associated with the type of treatment outcomes. CONCLUSIONS: In the study, the case-fatality rate was found to be very high. Therefore, there is a need to universal tetanus immunization and health information dissemination. PMID- 27386341 TI - Some properties for integro-differential operator defined by a fractional formal. AB - Recently, the study of the fractional formal (operators, polynomials and classes of special functions) has been increased. This study not only in mathematics but extended to another topics. In this effort, we investigate a generalized integro differential operator [Formula: see text] defined by a fractional formal (fractional differential operator) and study some its geometric properties by employing it in new subclasses of analytic univalent functions. PMID- 27386342 TI - Frequencies of ALK rearrangements in lung adenocarcinoma subtypes: a study of 2299 Chinese cases. AB - PURPOSE: This study aimed to determine the relationship between ALK status and lung adenocarcinoma subtypes, according to the IALSC/ATS/ERS classification in Chinese patients. METHODS: A reclassification of 2299 surgically resected lung adenocarcinomas was performed, and ALK status was detected by immunohistochemistry (Ventana Medical Systems) in Shanghai Chest Hospital. RESULTS: ALK rearrangements were identified in 93 of 2299 tumors (4.0 %). The ALK rearrangements frequencies were: 14.8 % (16/108), 10.3 % (20/195), 7.6 % (13/170), 2.8 % (29/1035), 2.5 % (3/119), 2.0 % (11/539), 0.9 % (1/114), and 0 % (0/19) for variants of invasive adenocarcinoma, solid predominant, micropapillary predominant, acinar predominant, minimally invasive adenocarcinoma, papillary predominant, lepidic predominant, and adenocarcinoma in situ, respectively. CONCLUSIONS: We reported significant discrepancies of ALK status in lung adenocarcinoma subtypes in Chinese patients. PMID- 27386343 TI - The income-based disparities in preeclampsia and postpartum hemorrhage: a study of the Korean National Health Insurance cohort data from 2002 to 2013. AB - There is limited evidence on the effects of relatively low socioeconomic status on maternal health. Additionally, the global economic recession that began in 2008 could have worsened disparities in maternal complications. To explore disparities in maternal health, we analyzed the occurrence of preeclampsia and postpartum hemorrhage according to level of household income. A population-based cohort data set from the Korean National Health Insurance was used to calculate the age-adjusted incidence, slope index of inequality, and Kunst and Mackenbach relative index of inequality (RIIKM) for preeclampsia and postpartum hemorrhage from 2002 to 2013. In the aggregated data of 65,479 live births, women with lower household income showed a higher risk of developing preeclampsia and postpartum hemorrhage than those with higherhigher incomes after adjusting for conventional risk factors. The absolute and relative inequalities for both complications showed no significant change over the period from 2002 to 2013. Considering the difference in the trends and risks of major obstetric complications according to level of household income, policies to monitor and reduce disparities in maternal health across different economic levels need to be implemented. PMID- 27386345 TI - Variable-intercept panel model for deformation zoning of a super-high arch dam. AB - This study determines dam deformation similarity indexes based on an analysis of deformation zoning features and panel data clustering theory, with comprehensive consideration to the actual deformation law of super-high arch dams and the spatial-temporal features of dam deformation. Measurement methods of these indexes are studied. Based on the established deformation similarity criteria, the principle used to determine the number of dam deformation zones is constructed through entropy weight method. This study proposes the deformation zoning method for super-high arch dams and the implementation steps, analyzes the effect of special influencing factors of different dam zones on the deformation, introduces dummy variables that represent the special effect of dam deformation, and establishes a variable-intercept panel model for deformation zoning of super high arch dams. Based on different patterns of the special effect in the variable intercept panel model, two panel analysis models were established to monitor fixed and random effects of dam deformation. Hausman test method of model selection and model effectiveness assessment method are discussed. Finally, the effectiveness of established models is verified through a case study. PMID- 27386344 TI - A systematic review of association studies of common variants associated with idiopathic congenital talipes equinovarus (ICTEV) in humans in the past 30 years. AB - The genetic cause of idiopathic congenital talipes equinovarus (ICTEV) is largely unknown. We performed a systematic review to describe the findings from 21 studies that have examined the genetic variants related to ICTEV, and to evaluate the quality of reporting. We found that ICTEV was positively associated with Hox family genes, collagen family genes, GLI3, N-acetylation genes, T-box family genes, apoptotic pathway genes, and muscle contractile family genes. Negative and controversial results were also discussed, and several genes associated with ICTEV were identified. Due to the limitation of the included studies, rare coding variants should be further investigated, sample size should be enlarged, and candidate genes should be replicated in larger ICTEV populations. Epigenetic study, pathways, chromosome capture, and detailed gene-environment interaction will also allow further elucidation of factors involved in ICTEV pathogenesis and may shed light on diagnosis and timely and accurate interventions. PMID- 27386346 TI - The effect of discrepancy between radiologic size and pathologic tumor size in renal cell cancer. AB - To investigate the difference between preoperative radiologic tumor size (RTS) and postoperative pathologic tumor size (PTS) in patients who underwent nephrectomy for renal cell carcinoma. We retrospectively reviewed 257 patients who received preoperative computed tomography (CT) before radical or partial nephrectomy for renal cell carcinoma from January 2010 to May 2015 in Huashan Hospital, Shanghai. RTS was defined as the largest diameter of tumor measured by CT and PTS as the largest diameter of tumor measured in the surgical specimens. Among all subjects, mean RTS was larger than PTS (4.57 +/- 2.15 vs. 4.02 +/- 2.15 cm, P = 0.004) with a discrepancy of 0.55 cm. When the patients were categorized according to T stage, the mean RTS was greater than PTS in the following groups: <=4 cm group (2.90 vs. 2.59 cm, P = 0.02), >4 and <=7 cm group (5.08 vs. 4.38 cm, P < 0.0001), except for >7 cm (8.9 vs. 8.0 cm, P = 0.142). Among patients with clear cell RCC, the mean RTS was larger than the mean PTS (4.57 vs. 3.98 cm, P = 0.004), similar result was also seen in non-clear cell group (4.54 vs. 4.16 cm, P = 0.045). The mean RTS was larger than PTS for the approach of radical nephrectomy (RN) (5.26 vs. 4.64 cm, P = 0.01), but not for the partial nephrectomy (PN) (3.34 vs. 2.92 cm, P = 0.067). Of the 257 renal cancers, 76 tumors were down-staged when comparing radiographic and pathologic tumor maximal diameter. The proportion of down-staged tumors had no difference between different genders (P = 0.283), different surgery approaches (P = 0.102), and different pathology types (P = 0.209). In this study, we found that renal tumor size was overestimated by radiography compared with pathologic results, and the T staging of some tumors was down-staged. But for patients who underwent PN, there was no difference between RTS and PTS. These results suggested that the PN should be considered first for the T1b renal tumor when tumor size was close to 4 cm, while the recommendation level of PN for T1b tumor was grade B according to EAU guidelines. PMID- 27386347 TI - Antibacterial activities and structure-activity relationships of a panel of 48 compounds from Kenyan plants against multidrug resistant phenotypes. AB - In the current study forty eight compounds belonging to anthraquinones, naphthoquinones, benzoquinones, flavonoids (chalcones and polymethoxylated flavones) and diterpenoids (clerodanes and kauranes) were explored for their antimicrobial potential against a panel of sensitive and multi-drug resistant Gram-negative and Gram-positive bacteria. The minimal inhibitory concentration (MIC) determinations on the tested bacteria were conducted using modified rapid INT colorimetric assay. To evaluate the role of efflux pumps in the susceptibility of Gram-negative bacteria to the most active compounds, they were tested in the presence of phenylalanine arginine beta-naphthylamide (PAbetaN) (at 30 ug/mL) against selected multidrug resistance (MDR) bacteria. The anthraquinone, emodin, naphthaquinone, plumbagin and the benzoquinone, rapanone were active against methicillin resistant Staphylococcus aureus (MRSA) strains of bacteria with MIC values ranging from 2 to 128 MUg/mL. The structure activity relationships of benzoquinones against the MDR Gram-negative phenotype showed antibacterial activities increasing with increase in side chain length. In the chalcone series the presence of a hydroxyl group at C3' together with a methoxy group and a second hydroxyl group in meta orientation in ring B of the chalcone skeleton appeared to be necessary for minimal activities against MRSA. In most cases, the optimal potential of the active compounds were not attained as they were extruded by bacterial efflux pumps. However, the presence of the PAbetaN significantly increased the antibacterial activities of emodin against Gram negative MDR E. coli AG102, 100ATet; K. pneumoniae KP55 and KP63 by >4-64 g/mL. The antibacterial activities were substantially enhanced and were higher than those of the standard drug, chloramphenicol. These data clearly demonstrate that the active compounds, having the necessary pharmacophores for antibacterial activities, including some quinones and chalcones are substrates of bacterial efflux pumps and therefore should be combined to efflux pump inhibitors in the fight against MDR bacterial infections. PMID- 27386348 TI - Impact of adjustable cryogel properties on the performance of prostate cancer cells in 3D. AB - BACKGROUND: Biochemical and physical characteristics of extracellular environment play a key role in assisting cell behavior over different molecular pathways. In this study, we investigated how the presence of chemical binding sites, the pore network and the stiffness of designed scaffolds affected prostate cancer cells. METHODS: A blend of poly hydroxyethyl methacrylate-alginate-gelatin scaffold was synthesized by cryogelation process using polyethyleneglycol diacrylate (PEGda) and glutaraldehyde as cross linkers. The chemical and mechanical scaffold properties were varied by concentration of gelatin and PEGda, respectively. The pore network was modified by applying different 'freezing time'. Growth, spheroid formation and localization of androgen receptor (AR) were measured to evaluate cell response within various cryogel types. RESULTS: Insufficient porosity in combination with a brittle nature affects cell growth negatively. Spheroid size was reduced by porosity, elasticity as well as by the absence of the cell adhesive motif composed of arginine, glycine und aspartic acid (RGD). Localization of AR indicates its activity and should be under normal culture conditions in the nucleus. But in this study, we could investigate for the first time that AR remains in the cytoplasm when AR positive prostate cancer cells are cultured in scaffolds without RGD as well as in case of an insufficient pore network (total porosity under 10 %) and a too less stiffness of around 10 kPa. CONCLUSIONS: The results indicate that for getting a reliable preclinical drug screening a three-dimensional prostate model system with appropriate biochemical and physical surrounding is needed. PMID- 27386349 TI - Editorial behaviors in peer review. AB - Editors play a critical role in the peer review system. How do editorial behaviors affect the performance of peer review? No quantitative model to date allows us to measure the influence of editorial behaviors on different peer review stages such as, manuscript distribution and final decision making. Here, we propose an agent-based model in which the process of peer review is guided mainly by the social interactions among three kinds of agents representing authors, editors and reviewers respectively. We apply this model to analyze a number of editorial behaviors such as decision strategy, number of reviewers and editorial bias on peer review. We find out that peer review outcomes are significantly sensitive to different editorial behaviors. With a small fraction (10 %) of biased editors, the quality of accepted papers declines 11 %, which indicates that effects of editorial biased behavior is worse than that of biased reviewers (7 %). While several peer review models exist, this is the first account for the study of editorial behaviors that is validated on the basis of simulation analysis. PMID- 27386350 TI - Characteristics of safety information obtained from postmarketing observational studies for re-examination in Japan. AB - BACKGROUND: In Japan, postmarketing surveillance (PMS) studies are required for newly approved drug products to further collect safety information in clinical settings. "PMS study" is a general term encompassing both postmarketing observational (PMO) studies and postmarketing intervention studies for re examination. Each PMS study is conducted under contracts between the pharmaceutical company and medical institutions in accordance with Good Postmarketing Study Practice. It has been reported that the safety information collected postmarketing is limited because of underreporting. The objective of this investigation was to identify differences among profiles of the drug product safety information collected through intervention studies and observational studies before and after approval. Our study addressed whether the issue of underreporting, generally considered as associated with observational studies, occurs in PMO studies for re-examination. In addition, we considered potential causes of such underreporting. RESULTS: The overall adverse reaction rate was lower in PMO studies than in intervention studies before approval in almost all cases. The adverse reaction rate in intervention studies exhibited similar profiles regardless of whether they were conducted prior to or following approval. In addition, we found that one reason for a lower adverse reaction rate in PMO studies was that the number of reports of adverse reactions that had occurred frequently prior to approval decreased postmarketing. CONCLUSIONS: Underreporting was observed even in PMO studies for re-examination under the Japanese regulation. Although it was suggested that expected and common adverse reactions were more likely to be subject to underreporting, further investigation is warranted to explore the reasons for the under-reporting in PMO studies. PMID- 27386351 TI - Evaluation of sphenopalatine ganglion blockade via intra oral route for the management of atypical trigeminal neuralgia. AB - BACKGROUND: The sphenopalatine ganglion (SPG) may be involved in persistent idiopathic facial pain and unilateral headaches. The role of SPG blockade via intra oral route in the management of trigeminal neuralgia (TN) is worthy of study. METHODS: In this retrospective study, patient records included patients with atypical TN (type 2) that persisted in spite of conservative treatment for at least 2 years, and an average pain intensity from the craniofacial region visual analogue scale (VAS) before examination. In group I the patients received carmapazepin 800 mg a day for at least 2 years. In group II 3 ml of local anesthetic agent consisting 2 ml bupivacaine and 1 ml prilocain in addition to 1 ml fentanyl, 0.5 ml betametasone disodium phosphate and 0.5 ml opaque was injected by the intraoral route. In this group, injection procedures were performed under local anesthesia with fluoroscopic guidance. The Kruskal-Wallis and Mann-Whitney U tests with Bonferroni correction were used for intergroup analysis. Age and sex differences were evaluated with one-way ANOVA and Fisher's exact tests, respectively. RESULTS: Significant differences were found between pre-op and 3rd day VAS values and also pre-op and 1st month VAS values. No significant differences were found between pre-op and 6th month VAS values. CONCLUSION: The SPG blockade improves the quality of life of patients and a minimally-invasive procedure to management of TN, when compared to other methods. PMID- 27386352 TI - Dietary effects of lutein-fortified chlorella on milk components of Holstein cows. AB - This study was conducted to investigate the dietary effect of conventional or lutein-fortified chlorella on milk production and lutein incorporation in milk. Fifteen Holstein cows in mid-lactation were used in a 3 * 3 Latin square design each with a 21-day period. Cows were top-dressed daily with 30 g of conventional or lutein-fortified chlorella for 3 weeks. Cows without chlorella served as the control. The feed intake and milk yield were not affected by dietary treatments. The concentrations of milk protein and solids non-fat in groups fed diets containing both conventional and lutein-fortified chlorella were significantly higher than those of the control group (P < 0.001). There was no significant difference in content of milk fat among groups. The levels of plasma glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, interferon-gamma and interleukin-2 were not influenced by the dietary treatments. Lutein content in milk was significantly increased in groups fed lutein-fortified chlorella as compared with those of conventional chlorella and control, respectively (P < 0.01). These results imply that conventional and lutein-fortified chlorella has positive effects on milk components and the use of lutein-fortified chlorella in a dairy diet is effective in the production of milk enriched with lutein. PMID- 27386353 TI - Electrohydrodynamic (EHD) drying of the Chinese wolfberry fruits. AB - The conventional methods of drying Chinese wolfberry fruits cause loss of active ingredients and the drying time is very long. In order to explore and investigate the new method of drying Chinese wolfberry fruits, electrohydrodynamic (EHD) drying system was used to drying for Chinese wolfberry fruits with a multiple needle-to-plate electrode on five levels alternating voltage at 0, 20, 24, 28 and 32 kV and a multiple needle-to-plate electrode on a level direct voltage at 28 kV. The drying rate, the moisture rate, shrinkage rate, rehydration ratio, and Vitamin C contents of Chinese wolfberry were measured. Ten different mathematical drying models were also determined and compared to simulate drying curves based on the root mean square error, reduced mean square of the deviation and the coefficient of correlation. Each drying treatment was carried out at (25 +/- 2) degrees C, the drying relative humidity was (30 +/- 5) % and all samples were dehydrated until they reached the final moisture content (17 +/- 1)/100 g. The results showed that the drying rate of Chinese wolfberry was notably greater in the EHD system when compared to control, and improved by 1.8777, 2.0017, 2.3676 and 2.6608 times, respectively, at 20, 24, 28 and 32 kV, compared to that of the control in the 5 h. The drying rate with multiple needles-to-plate electrode under AC electric field is faster than that with a multiple needle-to-plate electrode under DC electric field and the mass transfer enhancement factor heightened with the increase of voltage. The EHD drying treatments have a significant effect on rehydration ratio, and Vitamin C contents of Chinese wolfberry, but no significant differences was observed in shrinkage rate of Chinese wolfberry. The specific energy consumption of EHD drying (kJ.kg(-1) water) were significantly influenced by the alternating voltage, it heightened with the increase of voltage. The Parabolic model was best suited for describing the drying rate curve of Chinese wolfberry fruits. Therefore, this work presents a facile and effective clue for experimentally and theoretically determining the EHD drying properties of Chinese wolfberry. PMID- 27386354 TI - Fractional calculus and application of generalized Struve function. AB - A new generalization of Struve function called generalized Galue type Struve function (GTSF) is defined and the integral operators involving Appell's functions, or Horn's function in the kernel is applied on it. The obtained results are expressed in terms of the Fox-Wright function. As an application of newly defined generalized GTSF, we aim at presenting solutions of certain general families of fractional kinetic equations associated with the Galue type generalization of Struve function. The generality of the GTSF will help to find several familiar and novel fractional kinetic equations. The obtained results are general in nature and it is useful to investigate many problems in applied mathematical science. PMID- 27386356 TI - Convergence theorems for generalized nonexpansive multivalued mappings in hyperbolic spaces. AB - In this paper, we establish the existence of a fixed point for generalized nonexpansive multivalued mappings in hyperbolic spaces and we prove some [Formula: see text]-convergence and strong convergence theorems for the iterative scheme proposed by Chang et al. (Appl Math Comp 249:535-540, 2014) to approximate a fixed point for generalized nonexpansive multivalued mapping under suitable conditions. Our results are the extension and improvements of the recent well known results announced in the current literature. PMID- 27386355 TI - Relationship between the microbiota in different sections of the gastrointestinal tract, and the body weight of broiler chickens. AB - In the poultry industry, many efforts have been undertaken to further improve the growth performance of broilers and identification and modulation of body weight (BW)-related bacteria could be one of the strategies to improve productivity. However, studies regarding the relationship between microbiota and BW are scarce. The objective of the present study was to investigate the relationship between microbiota and BW in different sections of the gastrointestinal tract (GIT). A total of twenty 18-day-old birds were selected based on the BW, and samples were collected from the three different sections of the GIT, which included the crop, ileum and cecum. Bacterial genomic DNA was extracted from the samples, and the V4 region of 16S rRNA gene were amplified. Amplicons were sequenced on Illumina MiSeq, and microbial communities were analyzed by using QIIME. In principal coordinate analysis, bacterial communities were clustered into three groups, based on the sections of GIT. Several BW-related bacterial groups were identified from linear regression analysis. At the genus level, Streptococcus from the ileum as well as Akkermansia in both ileum and cecum, were negatively related to BW, whereas Bifidobacterium in the ileum and Lactococcus in the cecum showed a positive correlation. The results from the present study showed that particular bacterial communities in the GIT were related to BW, and the study has broadened the understanding of the intestinal microbial ecosystem in broiler chickens. PMID- 27386357 TI - Natural deep eutectic solvents: cytotoxic profile. AB - The purpose of this study was to investigate the cytotoxic profiles of different ternary natural deep eutectic solvents (NADESs) containing water. For this purpose, five different NADESs were prepared using choline chloride as a salt, alongside five hydrogen bond donors (HBD) namely glucose, fructose, sucrose, glycerol, and malonic acid. Water was added as a tertiary component during the eutectics preparation, except for the malonic acid-based mixture. Coincidentally, the latter was found to be more toxic than any of the water-based NADESs. A trend was observed between the cellular requirements of cancer cells, the viscosity of the NADESs, and their cytotoxicity. This study also highlights the first time application of the conductor-like screening model for real solvent (COSMO-RS) software for the analysis of the cytotoxic mechanism of NADESs. COSMO-RS simulation of the interactions between NADESs and cellular membranes' phospholipids suggested that NADESs strongly interacted with cell surfaces and that their accumulation and aggregation possibly defined their cytotoxicity. This reinforced the idea that careful selection of NADESs components is necessary, as it becomes evident that organic acids as HBD highly contribute to the increasing toxicity of these neoteric mixtures. Nevertheless, NADESs in general seem to possess relatively less acute toxicity profiles than their DESs parents. This opens the door for future large scale utilization of these mixtures. PMID- 27386358 TI - A systematic determination of polyphenols constituents and cytotoxic ability in fruit parts of pomegranates derived from five Chinese cultivars. AB - Plant polyphenols derived from pomegranates are natural health-promoting components, and their bioactivities are well proved. However, the systematic studies of polyphenols constituents and cytotoxic ability in fruit parts of pomegranates derived from different Chinese cultivars have not been studied yet. In this report, a validated and sensitive HPLC-DAD method and fluorescence spectrophotometric method was established for quantitative analysis of four polyphenols and total phenolic content (TPC) in fruit parts of pomegranates (including peels, flesh, seeds, juices and leaves) derived from five Chinese cultivars, respectively. HPLC analysis was performed on the YMC ODS-A C18 column with gradient elution of MeOH and 0.1 % TFA. Four polyphenols including gallic acid, ellagic acid, punicalagin A&B and punicalin A&B exhibited satisfactory linearity in the concentration ranges of 20-320, 39-624, 74-1184 and 38-608 MUg/mL, respectively. The results demonstrated that the amounts of TPC and four polyphenols in different fruit parts of pomegranates varied significantly. Peels of Sour-YRP possessed the highest content of punicalagin A&B (125.23 mg/g), whereas other three polyphenols exhibited only trace. Among the five Chinese cultivars, Sour-YRP contained the highest content of TPC (688.61 mg/g) and could be considered as the desirable botanical source to obtain polyphenols. It is also discovered that low-maturity pomegranate might possessed much higher TPC than high-maturity pomegranate. The optimized HPLC-DAD method could be used for quality control of different pomegranates by identification and quantification of its main polyphenolic components. Furthermore, the in vitro cytotoxicity of different pomegranates fruit parts to cancer cells was evaluated. We discovered that peels and flesh extract of Sour-YRP significantly inhibited the proliferation of HepG2 and Hela cancer cells lines. The results of this work are promising for further investigation and development of pomegranates as therapeutic agent for the treatment of cancer. PMID- 27386359 TI - Prevalence of pathologies related to impacted mandibular third molars. AB - OBJECTIVE: Prevalence of cysts and tumors related to impacted third molars has been considered important because the risk justifies prophylactic extraction. This retrospective study aimed to evaluate the prevalence of cysts or tumors associated with impacted mandibular third molars (IMTMs) according to patients' age and gender. METHODS: Over the period from August 2006 to August 2011, 20,802 third molars from 17,535 patients were removed. Among these, IMTMs without cysts nor tumors were classified as non-pathology group, and IMTMs with cysts and tumors were classified into pathology group. The prevalence of IMTMs and associated cysts or tumors was analyzed in patient groups stratified by age and gender. The pathology group patients were also classified according to histopathological findings and the corresponding age groups. RESULTS: Radiographic signs of disease were detected for 176 lesions (0.846 %) in 165 patients. Of these, 135 (76.4 %) lesions were diagnosed as dentigerous cysts, 31 (17.6 %) as keratocysticodontogenic tumors, and 10 (5.7 %) as ameloblastomas. The prevalence of cysts or tumors tended to increase after 50 years of age, such as 7.27 % in 6th decades, 18.60 % in 7th decades, and 11.53 % in 8th decades, with a male predominance in older patients. CONCLUSIONS: IMTMs in old age patients more than 50 years old has high possibilities of developing cyst or tumors especially in male patients. However, these results should not be used as the only evidence for justifying prophylactic extraction, and further studies should investigate the survival rate of IMTMs without any pathologic in older populations. PMID- 27386360 TI - Metastatic cerebellar tumor of papillary thyroid carcinoma mimicking cerebellar hemangioblastoma. AB - INTRODUCTION: Well-differentiated papillary thyroid carcinoma generally (PTC) have a favorable prognosis. This metastasis is rare in the central nervous system. Brain metastasis has a relatively poor prognosis. We present a rare case of cerebellar metastasis, one that mimics a solid type cerebellar hemangioblastoma and because of which it was very hard to reach accurate preoperative diagnosis. Accurate diagnosis was challenging because of the similar imaging and histopathological findings for these two tumors. CASE DESCRIPTION: A brain lesion was detected by routine medical checkup of the brain with MRI in a 49-year-old woman 2 years after thyroidectomy for well-differentiated PTC. Gadolinium-enhanced MRI showed a homogeneous prominently enhanced lesion with surrounding enhanced dilated vessels in the left cerebellar hemisphere. Digital subtraction angiography showed a strongly stained lesion fed by the peripheral branch of the left posterior inferior cerebellar artery with drainage into the inferior vermian vein, revealing arteriovenous shunting. The most like likely preoperative diagnosis was felt to be that of a solid cerebellar hemangioblastoma. Gross total resection of the tumor was achieved by bilateral suboccipital craniotomy, and intraoperative pathological analysis suggested hemangioblastoma. Histopathological findings showed proliferation of vacuolated sheeted tumor cells with clear and eosinophilic cytoplasm and numerous thin walled microvessels, consistent with hemangioblastoma. However, the final diagnosis was brain metastasis of the follicular variant of PTC due to a partial thyroid follicle-like pattern including eosinophilic fluid pathologically and positive TTF-1 immunostaining. DISCUSSION AND EVALUATION: Since presented rare case of cerebellar metastasis of PTC was very similar to solid type cerebellar hemangioblastoma on imaging and histopathological findings, accurate diagnosis was challenging. Moreover, it is extremely rare for a cerebellar metastasis to occur as an initial distant metastasis of PTC, and hemangioblastoma is the most common primary cerebellar neoplasm in adults. This epidemiological data was also one of the reason of difficulty to reach preoperative accurate diagnosis. CONCLUSIONS: To the best of our knowledge, there are no other reports of challenging diagnosis case of these two tumors in the literature. Brain metastasis of a well-differentiated PTC could be a relatively poor prognostic factor, and accurate diagnosis and suitable surgical therapy or radiotherapy are needed. PMID- 27386361 TI - Travelling wave analysis in chemotaxis: case of starvation. AB - In this paper we investigate the existence of travelling wave solutions for a chemotaxis model under the scenarios of zero growth and constant growth rate. We use Lie symmetry analysis to generate generalized travelling wave solutions, a wider class of solutions than that obtained from the standard ansatz. Unlike previous approaches, we allow for diffusivity and signal degradation. We study the influence of cell growth, diffusivity and signal degradation on the behaviour of the system. We apply realistic boundary conditions to explicitly provide biologically relevant solutions. Our results generalize known results. PMID- 27386362 TI - Geostatistical characterization of the soil of Aguascalientes, Mexico, by using spatial estimation techniques. AB - Four spatial estimation techniques available in commercial computational packages are evaluated and compared, namely: regularized splines interpolation, tension splines interpolation, inverse distance weighted interpolation, and ordinary Kriging estimation, in order to establish the best representation for the shallow stratigraphic configuration in the city of Aguascalientes, in Central Mexico. Data from 478 sample points along with the software ArcGIS (Environmental Systems Research Institute, Inc. (ESRI), ArcGIS, ver. 9.3, Redlands, California 2008) to calculate the spatial estimates. Each technique was evaluated based on the root mean square error, calculated from a validation between the generated estimates and measured data from 64 sample points which were not used in the spatial estimation process. The present study shows that, for the estimation of the hard soil layer, ordinary Kriging offered the best performance among the evaluated techniques. PMID- 27386363 TI - Research on regularized mean-variance portfolio selection strategy with modified Roy safety-first principle. AB - We propose a consolidated risk measure based on variance and the safety-first principle in a mean-risk portfolio optimization framework. The safety-first principle to financial portfolio selection strategy is modified and improved. Our proposed models are subjected to norm regularization to seek near-optimal stable and sparse portfolios. We compare the cumulative wealth of our preferred proposed model to a benchmark, S&P 500 index for the same period. Our proposed portfolio strategies have better out-of-sample performance than the selected alternative portfolio rules in literature and control the downside risk of the portfolio returns. PMID- 27386364 TI - Genome-wide identification of soybean WRKY transcription factors in response to salt stress. AB - Members of the large family of WRKY transcription factors are involved in a wide range of developmental and physiological processes, most particularly in the plant response to biotic and abiotic stress. Here, an analysis of the soybean genome sequence allowed the identification of the full complement of 188 soybean WRKY genes. Phylogenetic analysis revealed that soybean WRKY genes were classified into three major groups (I, II, III), with the second group further categorized into five subgroups (IIa-IIe). The soybean WRKYs from each group shared similar gene structures and motif compositions. The location of the GmWRKYs was dispersed over all 20 soybean chromosomes. The whole genome duplication appeared to have contributed significantly to the expansion of the family. Expression analysis by RNA-seq indicated that in soybean root, 66 of the genes responded rapidly and transiently to the imposition of salt stress, all but one being up-regulated. While in aerial part, 49 GmWRKYs responded, all but two being down-regulated. RT-qPCR analysis showed that in the whole soybean plant, 66 GmWRKYs exhibited distinct expression patterns in response to salt stress, of which 12 showed no significant change, 35 were decreased, while 19 were induced. The data present here provide critical clues for further functional studies of WRKY gene in soybean salt tolerance. PMID- 27386365 TI - Successful closure of spontaneous esophageal rupture (Boerhaave's syndrome) by endoscopic ligation with snare loops. AB - INTRODUCTION: Spontaneous esophageal rupture is a rare condition with a high mortality rate, and it is generally treated by surgery. In the present report, successful non-surgical closure of spontaneous esophageal rupture by endoscopic ligation with snare loops in a patient with pyopneumothorax and septicemia is presented. CASE DESCRIPTION: The case of an 80-year-old man patient with spontaneous esophageal rupture who was cured by endoscopic ligation with snare loops is reported. The patient was admitted with severe chest pain. Chest CT scan revealed pneumomediastinum, and an upper gastrointestinal series using gastrografin showed leakage of contrast medium from the lower esophagus. Therefore, a diagnosis of spontaneous esophageal rupture to the thorax was made. Since the family refused surgery, the patient was treated conservatively. Since extensive blood in the stool was noted on day 5, an emergency endoscopic examination was performed. Clipping was performed around the perforation, and the clips were ligated with snare loops. The patient was discharged on day 83 without recurrence. DISCUSSION AND EVALUATION: We suggest that endoscopic ligation with snare loops should be chosen for elderly people and high-risk cases. PMID- 27386366 TI - An LFMCW detector with new structure and FRFT based differential distance estimation method. AB - This paper describes a linear frequency modulated continuous wave (LFMCW) detector which is designed for a collision avoidance radar. This detector can estimate distance between the detector and pedestrians or vehicles, thereby it will help to reduce the likelihood of traffic accidents. The detector consists of a transceiver and a signal processor. A novel structure based on the intermediate frequency signal (IFS) is designed for the transceiver which is different from the traditional LFMCW transceiver using the beat frequency signal (BFS) based structure. In the signal processor, a novel fractional Fourier transform (FRFT) based differential distance estimation (DDE) method is used to detect the distance. The new IFS based structure is beneficial for the FRFT based DDE method to reduce the computation complexity, because it does not need the scan of the optimal FRFT order. Low computation complexity ensures the feasibility of practical applications. Simulations are carried out and results demonstrate the efficiency of the detector designed in this paper. PMID- 27386367 TI - Esterification of glycerol from biodiesel production to glycerol carbonate in non catalytic supercritical dimethyl carbonate. AB - Conversion of glycerol from biodiesel production to glycerol carbonate was studied by esterification with dimethyl carbonate in a non-catalytic supercritical condition. It was found that in a non-catalytic supercritical condition, glycerol at higher purity gave higher yield of glycerol carbonate at 98 wt% after reaction at 300 degrees C/20-40 MPa/15 min. The yield of glycerol carbonate was observed to increase with molar ratio, temperature, pressure and time until a certain equilibrium limit. The existence of impurities such as water and remnants of alkaline catalyst in crude glycerol will direct the reaction to produce glycidol. Although impurities might not be desirable, the non-catalytic supercritical dimethyl carbonate could be an alternative method for conversion of glycerol from biodiesel production to value-added glycerol carbonate.Graphical abstractPlausible reaction scheme for conversion of glycerol to glycerol carbonate in non-catalytic supercritical dimethyl carbonate. PMID- 27386368 TI - Influence of long (16L:8D) and short (8L:16D) photoperiods on blood metabolites and hepatic metabolism in Olive flounder, Paralichthys olivaceus. AB - In the present study the influence of long photoperiod (LP, 16L:8D) and short photoperiod (SP, 8L:16D) on hepatic energy metabolism in the olive flounder (Paralichthys olivaceus) was investigated. Flounders were maintained under LP or SP conditions for 2 weeks then plasmatic and hepatic parameters were assessed. At the plasmatic level, the concentration of cortisol was enhanced in flounder maintained under LP compared to SP. Alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzyme activities in plasma also increased in LP flounder. There was no significant difference in plasma glucose levels between the two experimental groups. Plasma osmotic pressure, Na and Cl levels were significantly higher in LP compared to the SP group. In liver, a significant decrease of triglycerides together with an increase in glycogen was observed in the LP group. Hepatic hsl and pepck and muscle hsl mRNA expression in LP was significantly higher in the SP group. Overall the results indicate that the LP treatment caused a mild stress response and increased hepatic energy metabolism in the flounder, which in turn could affect osmoregulation. In conclusion, it would appear that LP treatment can adversely influence hepatic energy metabolism in adult olive flounder under fasting condition. PMID- 27386369 TI - How relevant is environmental quality to per capita health expenditures? Empirical evidence from panel of developing countries. AB - BACKGROUND: Developing countries have witnessed economic growth as their GDP keeps increasing steadily over the years. The growth led to higher energy consumption which eventually leads to increase in air pollutions that pose a danger to human health. People's healthcare demand, in turn, increase due to the changes in the socioeconomic life and improvement in the health technology. This study is an attempt to investigate the impact of environmental quality on per capital health expenditure in 125 developing countries within a panel cointegration framework from 1995 to 2012. RESULTS: We found out that a long-run relationship exists between per capita health expenditure and all explanatory variables as they were panel cointegrated. The explanatory variables were found to be statistically significant in explaining the per capita health expenditure. The result further revealed that CO2 has the highest explanatory power on the per capita health expenditure. The impact of the explanatory power of the variables is greater in the long-run compared to the short-run. Based on this result, we conclude that environmental quality is a powerful determinant of health expenditure in developing countries. CONCLUSION: Therefore, developing countries should as a matter of health care policy give provision of healthy air a priority via effective policy implementation on environmental management and control measures to lessen the pressure on health care expenditure. Moreover more environmental proxies with alternative methods should be considered in the future research. PMID- 27386370 TI - Analysis of credit linked demand in an inventory model with varying ordering cost. AB - In this paper, we have considered an economic order quantity model for deteriorating items with two-level trade credit policy in which a delay in payment is offered by a supplier to a retailer and also an another delay in payment is offered by the retailer to his/her all customers. Here, it is proposed that the demand function is dependent on the length of the customer's credit period and also the duration of offering the credit period. In this article, it is considered that the retailer's ordering cost per order depends on the number of replenishment cycles. The objective of this model is to establish a deterministic EOQ model of deteriorating items for the retailer to decide the position of customers credit period and the number of replenishment cycles in finite time horizon such that the retailer gets the maximum profit. Also, the model is explained with the help of some numerical examples. PMID- 27386371 TI - Simultaneous determination of six active metabolites in Astragalus mongholicus (Fisch.) Bge. under salt stress by ultra-pressure liquid chromatography with tandem mass spectrometry. AB - Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao (A. mongholicus, family Leguminosae) is one of the most important traditional Chinese herbs because it contains lots of bioactive metabolites, which have beneficial and pharmacological effects on health. Simultaneously, it has been proved to be a salt-tolerant plant-one of the potential species to control the soil salinization. Therefore, a sensitive and specific ultra-pressure liquid chromatography coupled with tandem mass spectrometric (UPLC-MS/MS) method was developed and validated for the simultaneous determination of six main bioactive metabolites, astragaloside IV, cycloastragenol, calycosin-7-O-beta-d-glucoside, calycosin, ononin and formononetin in different organs of A. mongholicus. The detection was accomplished by multiple-reaction monitoring (MRM) scanning via electrospray ionization source operating in the positive ionization mode. Calibration curves offered linear ranges of two orders of magnitude with R(2) > 0.99. The method was fully validated for the linearity, intra-day and inter day precisions, accuracy, recovery, matrix effect and stability. Then this method was successfully applied to detect the content of major bioactive metabolites in different plant organs of A. mongholicus under salt stress. Significant variations in the content of six bioactive metabolites were observed after been processed by different levels of salinity in different part of plant. The results support for further exploration of the salt-tolerant mechanisms in A. mongholicus and its possibility as the species that control the soil salinization. Meanwhile, we established a UPLC-MS/MS assay of the trace components in seedling of A. mongholicus in this study. PMID- 27386372 TI - Modeling solubility and acid-base properties of some amino acids in aqueous NaCl and (CH3)4NCl aqueous solutions at different ionic strengths and temperatures. AB - New potentiometric experiments have been performed in NaCl and in (CH3)4NCl media, to determine the protonation constants, the protonation enthalpy changes and the solubility of six natural alpha-amino acids, namely Glycine (Gly), Alanine (Ala), Valine (Val), Leucine (Leu), Serine (Ser) and Phenylalanine (Phe). The aim of the work is the rationalization of the protonation thermodynamics (log [Formula: see text], solubility and [Formula: see text]) in NaCl, determining recommended, tentative or provisional values in selected experimental conditions and to report, for the first time, data in a weak interacting medium, as (CH3)4NCl. Literature data analysis was performed selecting the most reliable values, analyzed together with new data here reported. Significant trends and similarities were observed in the behavior of the six amino acids, and in some cases it was possible to determine common parameters for the ionic strength and temperature dependence. In general, the first protonation step, relative to the amino group, is significantly exothermic (average value is [Formula: see text] = 44.5 +/- 0.4 kJ mol(-1) at infinite dilution and T = 298.15 K), and the second, relative to the carboxylate group, is fairly close to zero ([Formula: see text] = -2.5 +/- 1.6, same conditions). In both cases, the main contribution to the proton binding reaction is mainly entropic in nature. For phenylalanine and leucine, solubility measurements at different concentrations of supporting electrolyte allowed to determine total and specific solubility values, then used to obtain the Setschenow and the activity coefficients of all the species involved in the protonation equilibria. The values of the first protonation constant in (CH3)4NCl are lower than the corresponding values in NaCl, due to the weak interaction between the deprotonated amino group and (CH3)4N(+). In this light, differences between the protonation functions in NaCl and (CH3)4NCl were used for the quantification of the stability of the weak [(CH3)4N(+)-L(-)] complexes that resulted log K = -0.38 +/- 0.07 as an average value for the six amino acids. PMID- 27386373 TI - Clinical characteristics of adverse reactions to nonionic low osmolality contrast media in patients transferred from the CT room to the emergency room. AB - Nonionic low osmolality contrast media (LOCMs) are used universally in computed tomography (CT) imaging. Although adverse reactions due to nonionic LOCMs are a common cause of emergency room (ER) admissions, few studies have investigated these adverse reactions. In the present study, we evaluated the characteristics of patients who were transferred from the CT room to the ER due to adverse reactions to contrast media, and we determined the risk factors for severe adverse reactions. A single-center retrospective study was conducted over a 41 month period. Baseline and clinical characteristics were evaluated and analyzed according to moderate and severe severity. In particular, risk factors of severe reactions were determined using logistic regression analysis. In total, 70 patients were admitted to the ER with adverse reactions due to nonionic LOCMs. Of these, 33 developed a moderate reaction, and 37 developed a severe reaction. Compared with the moderate reaction group, the severe reaction group was older, had higher blood pressures, showed more symptoms indicating the cardiovascular and central nervous system, and developed faster reactions to LOCMs. According to the multivariate logistic regression analysis, the age of the patient and time to onset of reaction demonstrated a statistical relationship with severe adverse reactions. In the receiver operating characteristic analysis, the optimal cutoff values for age and time to onset were 60 years and 5 min. In conclusion, clinicians should be attentive to anaphylaxis due to nonionic LOCM, in particular, for elderly patients aged older than 60 years and a time to reaction onset of less than 5 min. PMID- 27386374 TI - Effect of cobalt(II) chloride hexahydrate on some human cancer cell lines. AB - The present study investigates the anti-proliferative and apoptosis inducing mechanism of CoCl2.6H2O in PC-3 cancer cell line. Preliminary, three different forms of cobalt i.e., cobaltous (CoCl2.6H2O), macro-Co(II,III) oxide and nano Co(II,III) oxide were screened for antiproliferative activity in PC-3 cell line. The CoCl2.6H2O being the most effective antiproliferative agent, hence it was further tested against lung (A549), prostrate (PC-3) and brain (IMR-32) cell lines. Human embryonic kidney cell line (293T) was used as a normal cell line to compare the toxicity of CoCl2.6H2O. The CoCl2.6H2O induced morphological and anatomical changes in PC-3 cancer cell which were studied using light, confocal and scanning electron microscopy. The lactate dehydrogenase was estimated which showed mild necrotic mode of cell death. The Annexin/PI staining confirmed the apoptotic mode of cell death in PC-3 cells. Further, production of reaction of reactive oxygen species and changes in mitochondrial membrane potential was also assessed spectrofluorimetrically. The cell cycle arrest was also investigated using flow cytometery. Finally, the caspase activity was estimated in CoCl2.6H2O treated PC-3 cancer cell line. Interestingly, it was found that CoCl2.6H2O induces more cell death in cancerous cells as compared to normal non-cancerous cells. These findings presented CoCl2.6H2O as potential antiproliferative agent. PMID- 27386375 TI - Equation-Method for correcting clipping errors in OFDM signals. AB - Orthogonal frequency division multiplexing (OFDM) is the digital modulation technique used by 4G and many other wireless communication systems. OFDM signals have significant amplitude fluctuations resulting in high peak to average power ratios which can make an OFDM transmitter susceptible to non-linear distortion produced by its high power amplifiers (HPA). A simple and popular solution to this problem is to clip the peaks before an OFDM signal is applied to the HPA but this causes in-band distortion and introduces bit-errors at the receiver. In this paper we discuss a novel technique, which we call the Equation-Method, for correcting these errors. The Equation-Method uses the Fast Fourier Transform to create a set of simultaneous equations which, when solved, return the amplitudes of the peaks before they were clipped. We show analytically and through simulations that this method can, correct all clipping errors over a wide range of clipping thresholds. We show that numerical instability can be avoided and new techniques are needed to enable the receiver to differentiate between correctly and incorrectly received frequency-domain constellation symbols. PMID- 27386376 TI - Performance analysis of different surface reconstruction algorithms for 3D reconstruction of outdoor objects from their digital images. AB - 3D reconstruction of geo-objects from their digital images is a time-efficient and convenient way of studying the structural features of the object being modelled. This paper presents a 3D reconstruction methodology which can be used to generate photo-realistic 3D watertight surface of different irregular shaped objects, from digital image sequences of the objects. The 3D reconstruction approach described here is robust, simplistic and can be readily used in reconstructing watertight 3D surface of any object from its digital image sequence. Here, digital images of different objects are used to build sparse, followed by dense 3D point clouds of the objects. These image-obtained point clouds are then used for generation of photo-realistic 3D surfaces, using different surface reconstruction algorithms such as Poisson reconstruction and Ball-pivoting algorithm. Different control parameters of these algorithms are identified, which affect the quality and computation time of the reconstructed 3D surface. The effects of these control parameters in generation of 3D surface from point clouds of different density are studied. It is shown that the reconstructed surface quality of Poisson reconstruction depends on Samples per node (SN) significantly, greater SN values resulting in better quality surfaces. Also, the quality of the 3D surface generated using Ball-Pivoting algorithm is found to be highly depend upon Clustering radius and Angle threshold values. The results obtained from this study give the readers of the article a valuable insight into the effects of different control parameters on determining the reconstructed surface quality. PMID- 27386377 TI - Comparison of protein and energy supplementation to mineral supplementation on feeding behavior of grazing cattle during the rainy to the dry season transition. AB - The aim of this study was to evaluate the effects of protein-energy or mineral supplementation on the ingestive behavior of dairy steers on pasture in the post weaning phase during the rainy to dry season transition. Twenty-two 1/2 Holstein Zebu dairy steers with an average initial body weight of 234 +/- 16 kg were distributed into a completely randomized design into two groups: protein-energy supplementation and mineral supplementation offered ad libitum. The steers receiving protein-energy supplementation showed higher (P < 0.05) intake of dry matter (DM) and neutral detergent fiber (NDF) than those fed diets composed of mineral salt only. In addition, the animals that received protein-energy supplementation had longer period in grazing and spent on average more time per period eating at the trough (P < 0.05), however no significant differences were observed in the time per period in rumination and time per period in idle (P > 0.05). The supply of protein-energy supplement does not change the feeding behavior, except for an increase in the time spent feeding at the trough. The intake of protein-energy supplement improved the of DM and NDF feed efficiencies in grazing cattle during the rainy to the dry season transition. PMID- 27386378 TI - Phosphorylated-p38 mitogen-activated protein kinase expression is associated with clinical factors in invasive breast cancer. AB - PURPOSE: P38 mitogen-activated protein kinases (MAPK) level is an important prognostic factor in breast cancer. This study was performed to detect the expressions of P-p38 MAPK expression in breast cancer and explore their correlations with clinicopathological factors. EXPERIMENTAL DESIGN: Tumor samples from 355 Chinese patients diagnosed with invasive breast cancer and adjacent non cancerous tissue were collected between 2003 and 2010. The expression of P-p38 MAPK was analyzed using immunohistochemical staining. The correlations between P p38 MAPK expression and clinicopathological findings including age, AJCC Stage, Histologic characters, ER, PR, and HER2 were analyzed using the parametric correlation method. P-p38 MAPK was selected as dependent variable to perform multivariate analysis respectively at last. RESULTS: Overall, 161 (45 %) and 183 (52 %) of the 355 specimens showed positive P-p38 MAPK staining in the cytoplasm and nucleus respectively, which were significant higher than that in the adjacent non-cancerous tissues in both the cytoplasm and the nucleus. High P-p38 MAPK expression of cytoplasm and nucleus were both associated with positive PR status in luminal A/B type of breast cancer, and were both associated with positive HER2 status in HER2-positive type of breast cancer. The result of multivariate analysis demonstrated that HER2 and PR were both significantly association with P p38 MAPK expression of cytoplasm and nucleus. CONCLUSIONS: Our study suggests that P-p38 MAPK expression were significantly associated with clinicopathological factors and PR/HER2 might association with phosphorylation of p38 MAPK in different types of breast cancer. PMID- 27386379 TI - Dynamic effect of metro-induced vibration on the rammed earth base of the Bell Tower. AB - Xi'an Bell Tower (the Bell Tower) is a state-level ancient relic in China. The vibration caused by metro will exert adverse effect on the Bell Tower. This paper aims at presenting 3D-FEM models to predict the peak period velocity (PPV) of rammed earth base when the metro passing through the Bell Tower. The calculation results are compared with those of field test. Both results were found to be in good agreement. Furthermore, the results indicated that the effect of shock absorption measures is significant. The shock absorption tracks can obviously decrease the vibration of the Bell Tower, and the maximum decrease of PPV of the rammed earth base is 78.91 %. The proposed prediction has the potential to be developed as a decision and management tool for the evaluation of the risk associated with the influence of vibration caused by metro on buildings in urban areas. PMID- 27386380 TI - Genetic linkage map construction and QTL mapping of seedling height, basal diameter and crown width of Taxodium 'Zhongshanshan 302' * T. mucronatum. AB - Taxodium is a genus renowned for its fast growth, good form and tolerance of flooding, salt, alkalinity, disease and strong winds. In this study, a genetic linkage map was constructed using sequence-related amplified polymorphism (SRAP) and simple sequence repeat (SSR) markers based on an F1 population containing 148 individuals generated from a cross between T. 'Zhongshanshan 302' and T. mucronatum. The map has a total length of 976.5 cM, with a mean distance of 7.0 cM between markers, and contains 34 linkage groups with 179 markers (171 SRAPs and 8 SSRs). Quantitative trait loci (QTLs) affecting growth traits, such as seedling height, basal diameter and crown width, were detected based on the constructed linkage map. Four significant QTLs were identified, three of which, namely qtSH-1 for seedling height, qtBD-1 for basal diameter and qtCW-1 for crown width, were located at 2.659 cM of LG7 with logarithm odds values of 3.72, 3.49 and 3.93, respectively, and explained 24.9, 27.0 and 21.7 % of the total variation of the three grown traits, respectively. Another QTL for crown width (qtCW-2) was detected at 1.0 cM on LG13, with a logarithm of odds value of 3.15, and explained 31.7 % of the total variation of crown width. This is the first report on the construction of a genetic linkage map and QTL analysis in Taxodium, laying the groundwork for the construction of a high-density genetic map and QTL mapping in the genus Taxodium. PMID- 27386381 TI - Association of inflammatory gene polymorphisms with mechanical heart valve reoperation. AB - BACKGROUND: Various complications lead to reoperation in patients who undergo prosthetic valve replacement where inflammatory process could be involved. The goals of this study were to identify risk factors that correlate with reoperation in patients with prosthetic heart valves and to investigate the relationship between reoperation and inflammatory gene polymorphisms. RESULTS: The study included 228 patients from the EwhA-Severance Treatment Group of Warfarin. Single nucleotide polymorphisms of c-reactive protein (CRP), interferon-gamma, interleukin 1 beta, interleukin 6, interleukin 10, transforming growth factor beta 1, and tumor necrosis factor genes were genotyped by means of SNaPshot and TaqMan assays. Thirty-nine patients (17.1 %) underwent more than one heart valve operation. A threefold increased risk for heart valve reoperation was evident in homozygous variant-type (TT) carriers as compared with ancestral allele carriers of CRP rs1205. Logistic regression analysis revealed that CRP rs1205 (OR 2.68, 95 % CI 1.22-5.90, p = 0.014), valve position (mitral valve OR 2.80, 95 % CI 1.01 7.80, p = 0.048; tricuspid valve OR 9.24, 95 % CI 2.46-34.70, p = 0.001; reference: aortic valve) and time after first operation (OR 1.13, 95 % CI 1.06 1.20, p < 0.001) affected the risk of reoperation. CONCLUSIONS: Inflammatory gene polymorphisms could be a possible marker of risk for reoperation in patients with prosthetic heart valve surgery. PMID- 27386382 TI - Prevalence and characteristics of chronic body pain in China: a national study. AB - BACKGROUND: Chinese citizens regularly experience some form of bodily pain, yet little is known regarding the epidemiology of pain. METHODS: We conducted a nationally representative sample cross sectional study to estimate the prevalence of pain and identify risk factors of pain among 19,665 community residents aged 18-65 years in China. The China Sub-optimal Health Survey (CSHS) data was used to estimate pain prevalence. Body pain was also estimated by self-reports from the sample population. A logistical regression model was applied to estimate the odds ratio and 95 % CIs of acute pain and chronic pain to explore the potential risk factors. RESULTS: Women had a higher prevalence of pain than men (39.92 vs. 32.17 % for chronic pain). The prevalence of pain increased with age (29.72 % for ages 18-25 vs. 42.23 % for ages 45-65). The most common complaints were head, neck/shoulder, and waist/back pain. Females (OR 1.57, 95 % CI 1.44-1.71) ages 25 or older (25-45: OR 1.19, 95 % CI 1.04-1.36; 45-65: OR 1.47, 95 % CI 1.26-1.73) were more likely to report having chronic pain. Subjects' living areas, and their drinking status (OR 1.32, 95 % CI 1.13-1.53) or smoking status (OR 1.01, 95 % CI 0.91-1.11), were also factors that were significantly associated with increased reporting of chronic pain. CONCLUSION: Women had a higher prevalence of chronic pain than men, although both sexes had a high prevalence for chronic pain. There were significant differences between the two sexes and the location of chronic pain in the body, most notably in the shoulders, stomach, abdomen, and waist. PMID- 27386383 TI - Clinical malaria diagnosis: rule-based classification statistical prototype. AB - In this study, we identified predictors of malaria, developed data mining, statistically enhanced rule-based classification to diagnose malaria and developed an automated system to incorporate the rules and statistical models. The aim of the study was to develop a statistical prototype to perform clinical diagnosis of malaria given its adverse effects on the overall healthcare, yet its treatment remains very expensive for the majority of the patients to afford. Model validation was performed using records from two hospitals (training and predictive datasets) to evaluate system sensitivity, specificity and accuracy. The overall sensitivity of the rule-based classification obtained from the predictive dataset was 70 % [68-74; 95 % CI] with a specificity of 58 % [54-66; 95 % CI]. The values for both sensitivity and specificity varied by age, generally showing better performance for the data mining classification rules for the adult patients. In summary, the proposed system of data mining classification rules provides better performance for persons aged at least 18 years. However, with further modelling, this system of classification rules can provide better sensitivity, specificity and accuracy levels. In conclusion, using the system provides a preliminary test before confirmatory diagnosis is conducted in laboratories. PMID- 27386384 TI - Nonsurgical periodontal treatment reduced aortic inflammation in ApoE(-/-) mice with periodontitis. AB - BACKGROUND: Although the correlation between periodontal infection and atherosclerotic lesions has been well recognized, whether and how the nonsurgical periodontal treatment (NSPT) can improve the vascular inflammation has not been investigated clearly. METHODS: Thirty-two apolipoprotein E(-/-) (apoE(-/-)) mice were randomly divided into four groups: (1) Con group: no treatment, blank control group; (2) Lig group: ligature-induced-periodontitis group; (3) Lig-N group: ligatures were removed on the 7th day; (4) Lig-SRP group: ligatures were removed on the 7th day, and scaling and root planing (SRP) were performed on the 9th day. All the animals were euthanized on the 30th day. Alveolar bone loss (ABL) was assessed under microcomputed tomography. Systemic inflammatory status and lipid contents in the plasma were detected. Expression of several surrogate markers for vascular inflammation was evaluated by immunohistology and quantitative real time PCR. RESULTS: NSPT reduced ABL, improved lipid profile, and inhibited systemic inflammation with reduced plasma interleukin-6 (IL-6) level in apoE(-/-) mice; in addition, reduced inflammation in arterial wall was observed in NSPT treated mice, showing less vascular cell adhesion molecule-1 expression and less macrophage adhesion; furthermore, NSPT improved elastic fiber fragmentation disorder in the aortic wall, thus preserved elasticity of aortic artery. CONCLUSION: Ligature-induced periodontitis can lead to inflammatory response in the vascular wall and NSPT has beneficial effect on the early stage of atherosclerosis process in the articular wall by reducing systemic inflammation and improving lipid profile. PMID- 27386385 TI - Strong convergence theorems for a common zero of a finite family of H-accretive operators in Banach space. AB - The aim of this paper is to study a finite family of H-accretive operators and prove common zero point theorems of them in Banach space. The results presented in this paper extend and improve the corresponding results of Zegeye and Shahzad (Nonlinear Anal 66:1161-1169, 2007), Liu and He (J Math Anal Appl 385:466-476, 2012) and the related results. PMID- 27386386 TI - Computing symmetrical strength of N-grams: a two pass filtering approach in automatic classification of text documents. AB - The contiguous sequences of the terms (N-grams) in the documents are symmetrically distributed among different classes. The symmetrical distribution of the N-Grams raises uncertainty in the belongings of the N-Grams towards the class. In this paper, we focused on the selection of most discriminating N-Grams by reducing the effects of symmetrical distribution. In this context, a new text feature selection method named as the symmetrical strength of the N-Grams (SSNG) is proposed using a two pass filtering based feature selection (TPF) approach. Initially, in the first pass of the TPF, the SSNG method chooses various informative N-Grams from the entire extracted N-Grams of the corpus. Subsequently, in the second pass the well-known Chi Square (chi(2)) method is being used to select few most informative N-Grams. Further, to classify the documents the two standard classifiers Multinomial Naive Bayes and Linear Support Vector Machine have been applied on the ten standard text data sets. In most of the datasets, the experimental results state the performance and success rate of SSNG method using TPF approach is superior to the state-of-the-art methods viz. Mutual Information, Information Gain, Odds Ratio, Discriminating Feature Selection and chi(2). PMID- 27386387 TI - Is DVT prophylaxis necessary after oncology lower limb surgery? A pilot study. AB - BACKGROUND: Deep vein thrombosis (DVT) has been independently associated with both malignant diseases and orthopaedic surgery. Therefore, orthopaedic oncology patients may be at a high risk for thromboembolic events. However, less emphasis is given to this group of patients compared to the patients undergoing total hip and knee replacement. The objective of this study is to determine the incidence of DVT and their risk factors in patients undergoing orthopaedic oncology lower limb surgery without prophylaxis. QUESTIONS/PURPOSES: (1) What is the incidence of DVT in patients who underwent orthopaedic oncology surgery for the lower limb? (2) What are the risk factors related to DVT in patients who underwent oncology surgery of the lower limb surgery? (3) This is a pilot study to determine if further trial is warranted. METHODS: This is a prospective study. All sequential patients undergoing orthopaedic oncology operations from the period of 1st October 2013 till 30th September 2014 were recruited for the study with their consent. Their demographic data, diagnosis and surgery were documented. Thirty eight patients who underwent lower limb surgeries for orthopaedic oncology indications were included in the study. No tourniquet was used in these lower limb surgeries. There were 24 men and 14 women with a mean age of 36 years (11 75). All potential risk factors were also identified and documented. All patients were not given any form of DVT prophylaxis (mechanical and chemical) before and after operation as this is a standard protocol in our center and a Medical Ethics Committee approval was taken for this study. DVT surveillance was performed 1 day before operation and 2 weeks after operation with ultrasound Doppler. Patients diagnosed with DVT via ultrasound Doppler were subsequently scheduled for CTPA to look for pulmonary embolism (PE). RESULTS: DVT was detected in two patients (5 %). Both patients were asymptomatic and they both had proximal thrombosis. One patient (2.6 %) was diagnosed with non-fatal PE and was asymptomatic. PE was detected incidentally by staging computed tomography scan and the patient had negative ultrasound Doppler of the operated and non-operated limb for DVT. We did not carry out a statistical analysis as the study population with DVT and pulmonary embolism is small. CONCLUSIONS: The incidence of DVT in patients after undergoing orthopaedic oncology lower limb surgery was low even without prophylaxis at our center. Further investigation with larger sample size is needed to validate our results and identify the risk factors. LEVEL OF EVIDENCE: Level III descriptive study. PMID- 27386388 TI - The Indian Basket Trick: a case of delayed paraplegia with complete recovery, caused by misplaced thoracic pedicle screw. AB - INTRODUCTION: Pedicle screw fixation allows purchase of all three spinal columns without encroaching into the spinal canal improving fracture fixation, as well as deformity correction. Fortunately, neurologic injury associated with pedicle screw malposition is rare. CASE PRESENTATION: A 19-year-old boy was surgically treated for severe right thoracic scoliosis associated with a Chiari Type 1 malformation and a C6 to T7 syringomyelia. Six months after the initial surgery, the patient was referred to our institution after three weeks of gait disturbances and repeated falls. Imaging showed the gross misplacement of the left T5 pedicle screw, which crossed the center of the vertebral canal. The initial surgery used a freehand technique of pedicle screw insertion, with anteroposterior and lateral postoperative X-ray control. During the surgery, no SEP modifications were noted during pedicle screw placement. However, after insertion of the second rod and scoliosis correction by posterior translation technique, SEP responses decreased considerably. Revision surgery was performed to remove the misplaced screw. During the first three months after screw removal, repeated clinical examinations showed progressive recovery of the neurological deficits. Gait and bladder functions were normal six months after screw removal, and clinical signs of spasticity disappeared. SEP explorations performed at final follow-up showed similar responses to those performed before the initial surgery for scoliosis correction. DISCUSSION AND EVALUATION: Neurologic injury associated with pedicle screw malposition is rare. In early or delayed neurological status worsening, intraoperative or postoperative imaging must be done to detect pedicle screw misplacement. In the current case, thanks to cobalt-chromium and titanium use, MRI and CT scan allowed good visualization of the spinal canal and spinal cord. Experimental studies have shown that neurophysiological monitoring of the spinal cord does not detect moderate compression. In that way, neurophysiological monitoring is an all-or-nothing technique which can misdiagnose early stage of spinal cord injuries. Major penetration of the spinal canal by pedicle screw may conduct to hardware removal. CONCLUSIONS: In early or delayed neurological status worsening, intraoperative or postoperative imaging must be done to detect pedicle screw misplacement. In the current case, thanks to cobalt-chromium and titanium use, MRI and CT scan allowed good visualization of the spinal canal and spinal cord. Major penetration of the spinal canal by pedicle screw may conduct to hardware removal. PMID- 27386389 TI - Pipe flow of pumping wet shotcrete based on lubrication layer. AB - Wet shotcrete can reduce dust and improve supporting strength, however, safe and efficient pipage is a key technical part of wet shotcrete process. The paper studied the pipe flow law of wet shotcrete based on lubrication layer by build the experimental pumping circuit of wet shotcrete that can carry out a number of full-scale pumping tests. The experimental results show there was a linear relationship between pressure loss and flow rate. Combined with the Buckingham rheological equation, the computing equations of the yield shear stress and plastic viscosity were deduced through linear regression. A simple analytical method allowing for a rough estimation of the pumping pressure was proposed and used when considering the lubrication layer of wet shotcrete in pipes. In addition, two kinds of particulate distributive models were established along the time axial to analyze the formation of lubrication layer which is related with particles migration. By computational fluid dynamics simulation, the lubrication layer thickness of different mix proportions was estimated. A new method for measuring the thickness of lubrication layer was proposed to verify it by binarization processing. Finally, according to the comparative analysis of experiments, simulation and computed value, it can be seen that the lubrication layer plays a key role in the process of wet shotcrete flow and with the increase of lubrication layer thickness pipe pressure declines gradually. PMID- 27386390 TI - A rational cubic trigonometric approximation scheme of the generalized Cornu spirals. AB - The [Formula: see text] and [Formula: see text]-approximation schemes are introduced to approximate the popular generalized Cornu spirals with the help of the parametric rational cubic trigonometric Bezier curves. The [Formula: see text]-approximation scheme has two free parameters whereas [Formula: see text] approximation scheme has four free parameters. To approximate the generalized Cornu spirals, the values of these free parameters are optimized by the minimization of the maximum relative curvature error of approximation. By comparing the relative curvature errors of approximation schemes, the developed approximation schemes are found less erroneous and more efficient than the existing GCS approximation schemes. PMID- 27386391 TI - A randomized phase I trial of nanoparticle albumin-bound paclitaxel with or without mifepristone for advanced breast cancer. AB - PURPOSE: Glucocorticoid receptor (GR) overexpression is associated with poor prognosis ER-negative breast cancer. GR antagonism with mifepristone increases chemotherapy-induced breast cancer cell death, therefore we conducted a phase I clinical trial of mifepristone and nab-paclitaxel in advanced breast cancer. METHODS: A novel randomized phase I design was used to assess the effect of mifepristone on nab-paclitaxel pharmacokinetics and toxicity. Patients were randomized to placebo or mifepristone for the first cycle; mifepristone was given to all for subsequent cycles. RESULTS: Nine patients were enrolled. All were found to have a twofold or greater increase in serum cortisol after mifepristone administration, reflecting effective GR inhibition. Neutropenia occurred at both nab-paclitaxel dose levels studied (100 and 80 mg/m(2)), and was easily managed with dose reduction and/or growth factor administration. Pharmacokinetic data suggest an interaction between nab-paclitaxel and mifepristone in some patients. Two patients had complete responses (CR), three partial responses (PR), one stable disease (SD), and three progressive disease (PD). Immunohistochemical staining for GR found six of nine tumors were GR-positive. All six GR-positive tumors were triple-negative at the time of recurrence. Of these six patients, two had CRs, two PRs, one SD, and one PD. CONCLUSIONS: GR appears to be a promising target in TNBC, and GR inhibition plus chemotherapy produces manageable toxicity. While neutropenia was observed in some, a nab-paclitaxel dose of 100 mg/m(2) plus mifepristone 300 mg was found to be tolerable, and a randomized phase II trial of nab-paclitaxel with/without mifepristone is planned in GR-positive advanced TNBC. PMID- 27386392 TI - Evaluation of Brevibacillus brevis as a potential plant growth promoting rhizobacteria for cotton (Gossypium hirsutum) crop. AB - The present investigation was undertaken to isolate, screen and evaluate a selected promising PGPR Brevibacillus brevis on cotton crop. Out of 156 bacterial isolates one of the most promising isolate was analyzed for the various PGP traits. A seed germination analysis was conducted with cotton seeds to evaluate the potential of the isolate to promote plant growth. The bacterial isolate was checked for its growth and survival at high temperatures. The isolate was also analyzed for the PGP traits exhibited after the heat treatment. To identify the isolate morphological, biochemical and molecular characterization was performed. The isolate was found positive for many of the PGP attributes like IAA, ARA, anti fungal activity and ammonia production. Effect of seed bacterization on various plant growth parameters was used as an indicator. The isolate showed significant growth and exhibited various PGP traits at high temperature making it suitable as an inoculant for cotton crop. Isolate was identified as Brevibacillus brevis [SVC(II)14] based on phenotypic as well as genotypic attributes and after conducting this research we propose that the B. brevis which is reported for the first time for its PGP potential in cotton, exerts its beneficial effects on cotton crop through combined modes of actions. PMID- 27386393 TI - Cultural transmission of civic attitudes. AB - In this empirical paper we attempt to measure the separate influence on civic engagement of educational attainment and cultural transmission of civic attitudes. Unlike most of the previous empirical works on this issue, we are able to approximate the cultural transmission of civic attitudes. We observe that civic returns to education are overstated when the transmission of civic attitudes is ignored. Moreover, the transmission of civic attitudes significantly enhances civic involvement and reinforces civic returns to education. Our findings are in line with the proposals of civic virtue theorists or grass movements who suggest that citizenship education should be included in the compulsory school curricula since, if not, families or local communities will only transmit their particular view of the world. PMID- 27386394 TI - Physical activity in light of affordances in outdoor environments: qualitative observation studies of 3-5 years olds in kindergarten. AB - This article examines the characteristic of affordances of different outdoor environments, related to the influences of children's physical activity levels. Qualitative observation studies in a Norwegian kindergarten were conducted of 3- to 5-year-olds into the natural environment and in the kindergarten's outdoor area. An ecological approach was important from both an analytical and theoretical point of view, using concepts from Gibson's (The ecological approach to visual perception. Houghton Mifflin Company, Bosten, 1979) theory of affordances. The concepts of affordances in an environment can explain children's movement behaviour. The findings reveal that situations with high physical activity levels among the children are more often created in natural environments than in the kindergarten's outdoor environment. Natural environments offer potential qualities that are a catalyst for physical activity. The study shows that certain characteristic of the physical outdoor environment are important for children's opportunities and inspiration for physical active play. The findings also show that social possibilities and opportunities, human interactions, in the environment have the greatest influence on the duration and intensity of physically active play. The need for knowledge on physical and social opportunities in outdoor environments, educational practice and the content of outdoor time in kindergartens should be given greater attention. PMID- 27386395 TI - Hepatocellular adenoma: comparison between real-time contrast-enhanced ultrasound and dynamic computed tomography. AB - PURPOSE: To investigate and compare the contrast-enhanced ultrasound (CEUS) features of histologically proven HCA with those of contrast-enhanced computed tomography (CECT). METHODS: Eighteen patients with proven hepatic adenoma by pathology were retrospectively selected from the CEUS database. Fourteen of them had undergone liver CECT exams. The basic features on unenhanced imaging and the enhancement level and specific features on contrast-enhanced imaging were retrospectively analyzed, and the differences between CEUS and CECT were compared. RESULTS: All the HCAs showed hyper-enhancement in the arterial phase. During the portal and late phases, 12 HCAs (12/18, 66.7 %) on CEUS and 11 (11/14, 78.6 %) on CT showed washout. On CEUS, 10 (10/18, 55.5 %) showed centripetal filling in the arterial phase and persistent peripheral rim enhancement. Five of them (61.1 %, 11/18) showed delayed central washout in the portal or late phase. However, on CECT, 2 (14.3 %, 2/14) and 4 (28.6 %, 4/14) HCAs showed persistent enhancement of the peripheral rim and central non-enhancing hemorrhage areas, respectively. CONCLUSIONS: Compared with dynamic CT, CEUS was superior at characterizing specific dynamic features. Considering that it is radiation-free, readily availability and easy to use, CEUS is suggested as the first line imaging tool to diagnose HCA. PMID- 27386396 TI - Prevention of intraocular pressure elevation with oleuropein rich diet in rabbits, during the general anaesthesia. AB - BACKGROUND: Oleuropein is known to have anti-oxidant and anti-inflammatory effects. An important aim of anesthetic management in ocular surgery is to keep the intraocular pressure under control. Studies have researched a variety of prophylactic materials used to prevent increases in intraocular pressure. We aimed to research the effects of oleuropein on intraocular pressure (IOP) during general anaesthesia. METHODS: Fourteen New Zealand rabbits were randomly divided into two groups of seven. The rabbits in Group O were given olive leaf extract (OLE) equivalent to a daily dose of 20 mg/kg oleuropein for 15 days. HPLC method used for oleuropein standardization. For anaesthesia induction 1 mg/kg rocuronium was given and after muscle relaxation all animals had a V-gel Rabbit inserted. Anesthetic maintenance was provided by 1 MAC isoflurane. Twenty minutes after rabbits were given 10 mg/kg ketamine, basal IOP values were measured. After the V gel rabbit was inserted, in the 5th, 10th, 20th, 25th and 30th minutes measurements were repeated. RESULTS: IOP data variation of OLE group was compared with control group and the measured levels were lower in Group O during the anaesthesia. IOP was 33.8 +/- 4 mmHg in Group C and 24.1 +/- 8 mmHg in Group O in 25th minute and the difference between the two groups was statistically significant at this time. CONCLUSION: We observed that consumption of prophylactic OLE had a reducing effect on IOP in the period before waking in anaesthesia. We believe it is necessary to investigate the effects of OLE on IOP in broad participation patient groups. PMID- 27386397 TI - The coordinating contracts of supply chain in a fuzzy decision environment. AB - The rapid change of the product life cycle is making the parameters of the supply chain models more and more uncertain. Therefore, we consider the coordination mechanisms between one manufacturer and one retailer in a fuzzy decision marking environment, where the parameters of the models can be forecasted and expressed as the triangular fuzzy variables. The centralized decision-making system, two types of supply chain contracts, namely, the revenue sharing contract and the return contract are proposed. To obtain their optimal policies, the fuzzy set theory is adopted to solve these fuzzy models. Finally, three numerical examples are provided to analyze the impacts of the fuzziness of the market demand, retail price and salvage value of the product on the optimal solutions in two contracts. It shows that in order to obtain more fuzzy expected profits the retailer and the manufacturer should seek as low fuzziness of demand, high fuzziness of the retail price and the salvage value as possible in both contracts. PMID- 27386398 TI - Computation of instant system availability and its applications. AB - The instant system availability [Formula: see text] of a repairable system with the renewal equation was studied. The starting point monotonicity of [Formula: see text] was proved and the upper bound of [Formula: see text] is also derived. It was found that the interval of instant system availability monotonically decreases. In addition, we provide examples that validate the analytically derived properties of [Formula: see text] based on the Lognormal, Gamma and Weibull distributions and the results show that the value of T is slightly smaller than its value defined in Theorem 2. The procedure of using a bathtub as application for this article is also discussed. PMID- 27386400 TI - On the existence of positive solutions for fractional differential inclusions at resonance. AB - In this paper, we discuss the existence of positive solutions for a boundary value problem of fractional differential inclusions with resonant boundary conditions. By using the Leggett-Williams theorem for coincidences of multi valued operators due to O'Regan and Zima, results on the existence of positive solutions are established. An example is given to illustrate the efficiency of the main theorems. PMID- 27386399 TI - Effect of thymoquinone on the healing of left colon anastomosis: an experimental study. AB - AIM: To evaluate the effect of thymoquinone on the healing of experimental left colon anastomosis in rats. METHODS: Forty Wistar albino rats weighing 250-300 g were randomly divided into four groups (10 rats/group). Group 1 (control group) rats were not administered Thymoquinone (TQ) for 3 days after the operation. Group 2 was administered daily TQ for 3 days starting from the first day after the operation. Group 3 was not administered TQ for 7 days after the operation. Group 4 was administered daily TQ for 7 days starting from the first day after the operation. Thymoquinone was administered as a single dose oral gavage through a 4F feeding catheter per each day. The bursting strength of the anastomosis was measured on 3rd and 7th postoperative days (POD) and resection was performed. Subsequently, the hydroxyproline level in the resected tissue was measured and a histological evaluation was performed. RESULTS: The bursting pressures of the anastomoses were measured to be statistically significantly greater on 7th POD in TQ administered groups compared to those without TQ administration. Tissues were stained with Masson's trichrome dye in order to evaluate the amount of fibrous tissue reaction for histopathological examination; there was no significant difference in the amount of fibrous tissue between groups 1 and 2, while a very marked increase in the fibrous tissue was detected in groups 3 and 4. Mean tissue hydroxyproline levels of the groups 3 and 4 on 7th POD were 1.30 and 2.72 MUg/g protein, respectively. The difference between the groups was statistically significant (p = 0.001). CONCLUSIONS: TQ significantly increased the bursting pressure of the anastomosis, tissue hydroxyproline level, and fibrous tissue production. PMID- 27386401 TI - A simulation study of the impact of the public-private partnership strategy on the performance of transport infrastructure. AB - The choice of investment strategy has a great impact on the performance of transport infrastructure. Positive projects such as the "Subway plus Property" model in Hong Kong have created sustainable financial profits for the public transport projects. Owing to a series of public debt and other constraints, public-private partnership (PPP) was introduced as an innovative investment model to address this issue and help develop transport infrastructure. Yet, few studies provide a deeper understanding of relationships between PPP strategy and the performance of such transport projects (particularly the whole transport system). This paper defines the research scope as a regional network of freeway. With a popular PPP model, travel demand prediction method, and relevant parameters as input, agents in a simulation framework can simulate the choice of PPP freeway over time. The simulation framework can be used to analyze the relationship between the PPP strategy and performance of the regional freeway network. This study uses the Freeway Network of Yangtze River Delta (FN-YRD) in China as the context. The results demonstrate the value of using simulation models of complex transportation systems to help decision makers choose the right PPP projects. Such a tool is viewed as particularly important given the ongoing transformation of functions of the Chinese transportation sector, including franchise rights of transport projects, and freeway charging mechanism. PMID- 27386402 TI - miR-125b-1 is repressed by histone modifications in breast cancer cell lines. AB - PURPOSE: Downregulation of miR-125b-1 is associated with poor prognosis in breast cancer patients. In this work we investigated the effect of histone modifications on the regulation of this gene promoter. METHODS AND RESULTS: We evaluated the enrichment of two histone modifications involved in gene repression, H3K9me3 and H3K27me3, on the miR-125b-1 promoter in two breast cancer cell lines, MCF7 (luminal A subtype) and MDA-MB-231 (triple-negative subtype), compared to the non transformed breast cell line MCF10A. H3K27me3 and H3K9me3 were enriched in MCF7 and MDA-MB-231 cells, respectively. Next, we used an EZH2 inhibitor to examine the reactivation of miR-125b-1 in MCF7 cells and evaluated the transcriptional levels of pri-miR-125b-1 and mature miR-125b by qRT-PCR. pri-miRNA and mature miRNA transcripts were both increased after treatment of MCF7 cells with the EZH2 inhibitor, whereas no effect on miR-125b-1 expression levels was observed in MDA MB-231 and MCF10A cells. We subsequently evaluated the effect of miR-125b-1 reactivation on the expression and protein levels of BAK1, a target of miR-125b. We observed 60 and 70 % decreases in the expression and protein levels of BAK1, respectively, compared to cells that were not treated with the EZH2 inhibitor. We over-expressed KDM4B/JMJD2B to reactivate this miRNA, resulting in a three-fold increase in miR-125b expression compared with the same cell line without KDM4B/JMJD2B over-expression. CONCLUSION: The miR-125b-1 is repressed by different epigenetic mechanisms depending on the breast cancer subtype and that miR-125b-1 reactivation specifically eliminates the effect of repressive histone modifications on the expression of an pro-apoptotic target. PMID- 27386403 TI - Hemiarch versus total aortic arch replacement in acute type A dissection: a systematic review and meta-analysis. AB - BACKGROUND: Despite recent advances in aortic surgery, acute type A aortic dissection remains a surgical emergency associated with high mortality and morbidity. Appropriate management is crucial to achieve satisfactory outcomes but the optimal surgical approach is controversial. The present systematic review and meta-analysis sought to access cumulative data from comparative studies between hemiarch and total aortic arch replacement in patients with acute type A aortic dissection. METHODS: A systematic review of the literature using six databases. Eligible studies include comparative studies on hemiarch versus total arch replacement reporting short, medium and long term outcomes. A meta-analysis was performed on eligible studies reporting outcome of interest to quantify the effects of hemiarch replacement on mortality and morbidity risk compared to total arch replacement. RESULT: Fourteen retrospective studies met the inclusion criteria and 2,221 patients were included in the final analysis. Pooled analysis showed that hemiarch replacement was associated with a lower risk of post operative renal dialysis [risk ratio (RR) =0.72; 95% confidence interval (CI): 0.56-0.94; P=0.02; I(2)=0%]. There was no significant difference in terms of in hospital mortality between the two groups (RR =0.84; 95% CI: 0.65-1.09; P=0.20; I(2)=0%). Cardiopulmonary bypass, aortic cross clamp and circulatory arrest times were significantly longer in total arch replacement. During follow up, no significant difference was reported from current studies between the two operative approaches in terms of aortic re-intervention and freedom from aortic reoperation. CONCLUSIONS: Within the context of publication bias by high volume aortic centres and non-randomized data sets, there was no difference in mortality outcomes between the two groups. This analysis serves to demonstrate that for those centers doing sufficient total aortic arch activity to allow for publication, excellent and equivalent outcomes are achievable. Conclusions on differences in longer term outcome data are required. We do not, however, advocate total arch as a primary approach by all centers and surgeons irrespective of patient characteristics, but rather, a tailored approach based on surgeon and center experience and patient presentation. PMID- 27386404 TI - Guilt by association: a paradigm for detection of silent aortic disease. AB - Detection of clinically silent thoracic aortic aneurysm (TAA) is challenging due to the lack of symptoms (until aortic rupture or dissection occurs). A large proportion of TAA are identified incidentally while imaging a patient for other reasons. However, recently several clinical "associates" of TAA have been described that can aid in identification of silent TAA. These "associates" include intracranial aneurysm, aortic arch anomalies, abdominal aortic aneurysm (AAA), simple renal cysts (SRC), bicuspid aortic valve, temporal arteritis, a positive family history of aneurysm disease, and a positive thumb-palm sign. In this article we examine these associates of TAA and the data supporting their involvement with asymptomatic TAA. PMID- 27386405 TI - Acute aortic syndrome. AB - Acute aortic syndrome (AAS) is a term used to describe a constellation of life threatening aortic diseases that have similar presentation, but appear to have distinct demographic, clinical, pathological and survival characteristics. Many believe that the three major entities that comprise AAS: aortic dissection (AD), intramural hematoma (IMH) and penetrating aortic ulcer (PAU), make up a spectrum of aortic disease in which one entity may evolve into or coexist with another. Much of the confusion in accurately classifying an AAS is that they present with similar symptoms: typically acute onset of severe chest or back pain, and may have similar radiographic features, since the disease entities all involve injury or disruption of the medial layer of the aortic wall. The accurate diagnosis of an AAS is often made at operation. This manuscript will attempt to clarify the similarities and differences between AD, IMH and PAU of the ascending aorta and describe the challenges in distinguishing them from one another. PMID- 27386406 TI - The utility of the aortic dissection team: outcomes and insights after a decade of experience. AB - BACKGROUND: Mortality rates following acute type A aortic dissection (ATAAD) repair are reduced when operations are performed by a high-volume acute aortic dissection (AAD) team, leading to efforts to centralize ATAAD care. Here, we describe our experience with ATAAD repair by our AAD team over the last 10 years, with a focus on patient selection, transfer protocols, operative approach, and volume trends over time. METHODS: An AAD team was implemented at our institution in 2005, with dedicated high-volume AAD surgeons, a multidisciplinary approach to thoracic aortic disease management, and a standardized protocol for ATAAD repair. Further process improvements were made in 2013 to facilitate the rapid transfer of ATAAD patients to our institution using stream-lined triage, diagnostic, and transfer protocols for patients with suspected ATAAD (RACE-AD protocol). Volume trends and outcomes were assessed longitudinally over this period. RESULTS: Institutional ATAAD repair volume remained constant at 12+/-2 cases per year from 2005-2013, but increased nearly two-fold to 22+/-6 cases per year (P=0.004) from 2013-2015 following implementation of the RACE-AD protocol. To accommodate this increased volume, two additional surgeons were added to the AAD team. Surgeon ATAAD repair volume was unchanged over the 10-year interval (7.9+/-3.9 cases per year from 2005-2013 versus 5.5+/-1.5 cases per year from 2013-2015; P=0.36), and all AAD team surgeons consistently met or exceeded the high-volume surgeon threshold of 5 ATAAD repairs per year. Thirty-day/in-hospital mortality rates of less than 10% were maintained over the study period. CONCLUSIONS: Centralization of ATAAD care has begun to occur at our center, with maintenance of low mortality rates for ATAAD repair. These data confirm a net positive impact on regional ATAAD outcomes through transfer of patients to a high-volume center with dedicated AAD surgeons. PMID- 27386407 TI - Differential outcomes of type A dissection with malperfusion according to affected organ system. AB - BACKGROUND: The management of malperfusion in patients with acute Stanford type A aortic dissection is controversial. We sought to determine the rate of resolution of malperfusion following primary repair of the dissection and to identify anatomic sites of malperfusion that may require additional management. METHODS: We reviewed the hospital records of patients who presented to our institution with acute type A aortic dissection. Patient demographics, operative details and post-operative course were retrospectively extracted from our institutional electronic database. Depending upon the anatomic site, malperfusion was identified by a combination of radiographic and clinical definitions. Data were analyzed using standard univariable and multivariable methods. RESULTS: Between 1997-2013, 101 patients underwent repair of an acute type A dissection. Thirty day mortality was 14.9% (15/101); there were five intraoperative deaths. There was no difference in 30-day mortality between patients with or without malperfusion (15.4% vs. 14.7%, P=0.93). Twenty-five patients (24.7%), who survived surgery, presented with 31 sites of malperfusion. Anatomic sites included extremities [14], renal [10], cerebral [5] and intestinal [2]. Of these 31 sites, malperfusion resolved in 18 (58.1%) with primary aortic repair. Renal malperfusion resolved radiographically in 80.0%, with no difference in the incidence of insufficiency (44.0% vs. 35.2%; P=0.44) or dialysis (20.0% vs. 15.5%; P=0.61) between malperfusion and non-malperfusion patients. Extremity malperfusion resolved postoperatively in six out of 14 patients. Of the remaining eight, concomitant revascularization was performed in four, one had an amputation and three required postoperative interventions. Advanced patient age (OR: 1.06, 95% CI: 1.01-1.12, P=0.02) was an independent predictor of 30-day mortality, while preoperative malperfusion was not (OR: 0.77, 95% CI: 0.18-3.31, P=0.73). CONCLUSIONS: Malperfusion complicating acute type A dissection can be managed in many patients by aortic replacement alone with low overall mortality. Most cases of renal and cerebral malperfusion resolved following aortic surgery. Revascularization was frequently necessary in patients with extremity malperfusion. Patients presenting with intestinal ischemia had very poor outcomes. A patient-specific approach is recommended in such complex patients. PMID- 27386408 TI - Repair of type A dissection-benefits of dissection rota. AB - BACKGROUND: Acute type A aortic dissection repair is a surgical emergency associated with high mortality. In 2007, Liverpool Heart & Chest Hospital was the first institution in the United Kingdom to implement a thoracic aortic on-call dissection rota. We set out to investigate whether the dissection rota improved hospital quality outcomes and long-term survival. METHODS: Data from a prospectively collected database was analysed following case note validation. Two hundred patients underwent acute type A aortic dissection repair between October 1998 and November 2015. To assess the effect of the post-dissection rota on operative and postoperative outcomes, propensity matching of pre- and post dissection rota patients was used. RESULTS: Eighty patients were identified from the pre-dissection rota era and 120 from the post-dissection rota era. Sixty patients from each era were then propensity matched. Comparative analyses showed that patients who underwent acute type A dissection repair in the post-dissection rota period were less likely to suffer in-hospital mortality in both the matched and unmatched groups (30% vs. 13.3%; P=0.004 and 28.3% vs. 11.7%; P=0.055, respectively). A similar improvement was shown in acute renal failure (26.3% vs. 14.2%; P=0.033 and 31.7% vs. 15.0%; P=0.044, respectively). However, cardiopulmonary bypass times and aortic cross clamp times were still significantly longer in the matched post-dissection rota cohort. There was a significant improvement in 5-year survival for the pre- and post-dissection rota in both the matched and unmatched patients (P=0.004 and P=0.034). CONCLUSIONS: Reorganization of surgical expertise, activity and implementation of a dissection rota within our hospital have resulted in lower in-hospital mortality and better survival outcomes in this group of patients. PMID- 27386409 TI - Total aortic repair: the new paradigm in the treatment of acute type A aortic dissection. AB - The surgical management of acute type A aortic dissection (ATAAD) is in a period of rapid evolution. Understanding the complex physiology and anatomy of both acute and chronic dissection has been enhanced by the ready availability of state of the art imaging techniques. Technical advances in the intraoperative monitoring of organ perfusion, together with adjuncts to limit organ injury and increasing sophistication in open and endovascular surgery have led to a major reduction in both perioperative morbidity and mortality. In many centers, there has been a transition in mindset and surgical approach away from a purely central aortic operation focusing on the ascending aorta and a 'live to fight another day' philosophy. The current more global perspective recognizes the importance of aortic valve function, malperfusion, false lumen (FL) patency and the potential for future complex aneurysm development. The time is now right to transition into the next phase of sophistication in the management of ATAAD with the aim of achieving not only a safe acute operation, but to either entirely prevent chronic complications or to greatly simplify their management by the creation of an anatomical situation that facilitates future endovascular intervention in place of complex re-do surgery. We present our view on the evolution of surgery for ATAAD leading to our current technique of Branch First Arch replacement and Total Aortic Repair, which not only provides a safe immediate operation, but also offers the hope of a simplified future management if not a total cure for the pathology. PMID- 27386410 TI - Descending endograft for DeBakey type 1 aortic dissection: pro. AB - The surgical management of patients with DeBakey type 1 acute aortic dissection (DBT1-AAD) represents a major challenge for aortic surgeons. It has been demonstrated that the distal false lumen remains patent in about 70% to 80% of patients undergoing DBT1-AAD surgery and that a patent false lumen worsens the prognosis. In order to improve long term outcomes and reduce the frequency of late aneurysm formation and reoperation, a more aggressive primary operation involving total arch replacement (TAR) and concomitant antegrade stenting of the descending thoracic aorta (DTA) with a frozen elephant trunk (FET) has been introduced. Such extensive operations, however, remain controversial due to their increased technical complexity and perceived higher operative mortality and morbidity. This perspective article will overview the rationale behind, and the potential advantages and current evidence for, FET surgery in acute aortic dissection. PMID- 27386411 TI - Descending endografts for type A dissections: con. AB - An important goal of surgical repair of type A aortic dissection is to resect the intimal tear. Studies on the fate of residual dissection after acute type A aortic dissection repair in the past decade have driven surgeons to seek procedures to avoid distal reoperation. Aggressive surgical approach with total arch replacement in acute type A dissection has demonstrated lower incidence of distal reoperation and slower aortic growth rate compared to less aggressive ascending/hemiarch repair. Recently, successful results of thoracic endovascular aortic repair (TEVAR) in type B aortic dissection have encouraged surgeons to further attack acute type A aortic dissection with hybrid approach: antegrade endografting in the descending thoracic true lumen as an adjunct to hemiarch or total arch repair. However, is the hybrid approach with simultaneous descending endografting justified in all the acute type A aortic dissection cases? The outcomes of the hybrid approach reported by the several groups have demonstrated 80-100% of false lumen thrombus formation in the proximal descending aorta (stented segment); however, the complete obliteration of the false lumen is only 17-50%. The incidence of distal reoperation/reintervention after hybrid approach is as high as 14% and an adjunctive procedure is often performed. Moreover, there are concerns about additional risks associated with the hybrid procedures, such as spinal cord injury (SCI), stent graft induced new entry and stroke. The data on this new approach are still very limited. Hence, further study is warranted to prove its safety and durability. PMID- 27386412 TI - Surgical techniques in type A dissection. AB - Acute aortic dissection is a surgical emergency that must be urgently managed, with the primary goal of restoring flow to the dominant true lumen in the downstream aorta. Our preference at the Cleveland Clinic is for an open distal anastomosis technique without aortic clamping, as it permits more accurate approximation of dissected layers and more homeostatically secure anastomosis. During this procedure we employ right axillary end-to-side graft perfusion, followed by deep hypothermic circulatory arrest and antegrade brain perfusion. The distal anastomosis is performed without felt strips or glue. Critical to achieving a successful outcome is meticulous de-airing of the arch, diligent myocardial protection, and a water-tight anastomosis prior to discontinuing cardiopulmonary bypass. PMID- 27386413 TI - Surgical management of acute type A aortic dissection: branch-first arch replacement with total aortic repair. AB - Acute type A dissection (ATAAD) remains a morbid condition with reported surgical mortality as high as 25%. We describe our surgical approach to ATAAD and discuss the indications for adjunct techniques such as the frozen elephant trunk or complete aortic repair with endovascular methods. Arch replacement using the "branch-first technique" allows for complete root, ascending aorta, and arch replacement. A long landing zone is created for proximal endografting with a covered stent. Balloon-assisted intimal disruption and bare metal stenting of all residual dissected aorta to the level of the aortic bifurcation is then performed to obliterate the false lumen (FL) and achieve single true lumen (TL) flow. Additional branch vessel stenting is performed as required. PMID- 27386414 TI - Routine use of hemiarch during acute type A aortic dissection repair. PMID- 27386415 TI - Technical aspects of total aortic repair in the surgical management of acute type A aortic dissection. PMID- 27386416 TI - Frozen elephant trunk for DeBakey type 1 dissection: the Cleveland Clinic technique. PMID- 27386417 TI - Type A aortic dissection. PMID- 27386418 TI - Sedentary images in a popular US based parenting magazine: 2010-2015. AB - BACKGROUND: Parenting magazines serve as a platform for advertisers to target children and their caregivers. The purpose of this study was to analyze and describe the number of pictures of sedentary and non-sedentary children pictured in the popular parenting magazine, Parents. METHODS: Our sample consisted of 72 issues from Parents magazine from January 2010 to December 2015. The sampling frame consisted of all printed issues over this time period. All pictures of children, whether they were in advertisements or models appearing throughout the magazine were included. There were a total of 11 018 children images reviewed. RESULTS: The overwhelming majority included sedentary children (n = 9734, 88.3%), while the minority showed children engaged in some kind of activity (n = 1284, 11.7%). CONCLUSION: Parents are encouraged to discuss with their pediatricians which activities are most beneficial for their children's health. PMID- 27386419 TI - Testing multi-theory model (MTM) in predicting initiation and sustenance of physical activity behavior among college students. AB - BACKGROUND: Most college students do not adequately participate in enough physical activity (PA) to attain health benefits. A theory-based approach is critical in developing effective interventions to promote PA. The purpose of this study was to examine the utility of the newly proposed multi-theory model (MTM) of health behavior change in predicting initiation and sustenance of PA among college students. METHODS: Using a cross-sectional design, a valid and reliable survey was administered in October 2015 electronically to students enrolled at a large Southern US University. The internal consistency Cronbach alphas of the subscales were acceptable (0.65-0.92). Only those who did not engage in more than 150 minutes of moderate to vigorous intensity aerobic PA during the past week were included in this study. RESULTS: Of the 495 respondents, 190 met the inclusion criteria of which 141 completed the survey. The majority of participants were females (72.3%) and Caucasians (70.9%). Findings of the confirmatory factor analysis (CFA) confirmed construct validity of subscales (initiation model: chi2 = 253.92 [df = 143], P < 0.001, CFI = 0.91, RMSEA = 0.07, SRMR = 0.07; sustenance model: chi2= 19.40 [df = 22], P < 0.001, CFI = 1.00, RMSEA = 0.00, SRMR = 0.03). Multivariate regression analysis showed that 26% of the variance in the PA initiation was explained by advantages outweighing disadvantages, behavioral confidence, work status, and changes in physical environment. Additionally, 29.7% of the variance in PA sustenance was explained by emotional transformation, practice for change, and changes in social environment. CONCLUSION: Based on this study's findings, MTM appears to be a robust theoretical framework for predicting PA behavior change. Future research directions and development of suitable intervention strategies are discussed. PMID- 27386420 TI - Psycho-socioeconomic bio-behavioral associations on all-cause mortality: cohort study. AB - BACKGROUND: The purpose of this study was to examine the cumulative effects of psychological,socioeconomic, biological and behavioral parameters on mortality. METHODS: A prospective design was employed. Data from the 2005-2006 National Health and Nutrition Examination Survey (NHANES) were used (analyzed in 2015); follow-up mortality status evaluated in 2011. Psychological function was assessed from the Patient Health Questionnaire-9 (PHQ-9) as a measure of depression. Socioeconomic risk was assessed from poverty level, education, minority status, and social living status. Biological parameters included cholesterol, weight status, diabetes, hypertension and systemic inflammation. Behavioral parameters assessed included physical activity (accelerometry), dietary behavior, smoking status (cotinine) and sleep. These 14 psycho-socioeconomic bio-behavioral (PSBB) parameters allowed for the calculation of an overall PSBB Index, ranging from 0 14. RESULTS: Among the evaluated 2530 participants, 161 died over the unweighted median follow-up period of 70.0 months. After adjustment, for every 1 increase in the overall PSBB index score,participants had a 15% reduced risk of all-cause mortality (HR = 0.85; 95% CI: 0.76-0.96). After adjustment, the Behavioral Index (HR = 0.73; 95% CI: 0.60-0.88) and the Socioeconomic Index(HR = 0.82; 95% CI: 0.68-0.99) were significant, but the Psychological Index (HR = 0.67; 95%CI: 0.29 1.51) and the Biological Index (HR = 1.03; 95% CI: 0.89-1.18) were not. CONCLUSION: Those with a worse PSBB score had an increased risk of all-cause mortality.Promotion of concurrent health behaviors may help to promote overall well-being and prolong survival. PMID- 27386421 TI - Validation and psychometric evaluation of physical activity belief scale among patients with type 2 diabetes mellitus: an application of health action process approach. AB - BACKGROUND: Moderate increase in physical activity (PA) may be helpful in preventing or postponing the complications of type 2 diabetes mellitus (T2DM). The aim of this study was to assess the psychometric properties of a health action process approach (HAPA)-based PA inventory among T2DM patients. METHODS: In 2015, this cross-sectional study was carried out on 203 participants recruited by convenience sampling in Isfahan, Iran. Content and face validity was confirmed by a panel of experts. The comments noted by 9 outpatients on the inventory were also investigated. Then,the items were administered to 203 T2DM patients. Construct validity was conducted using exploratory and structural equation modeling confirmatory factor analyses. Reliability was also assessed with Cronbach alpha and interclass correlation coefficient (ICC). RESULTS: Content validity was acceptable (CVR = 0.62, CVI = 0.89). Exploratory factor analysis extracted seven factors (risk- perception, action self-efficacy, outcome expectancies, maintenance self-efficacy, action and coping planning, behavioral intention, and recovery self-efficacy) explaining 82.23% of the variation. The HAPA had an acceptable fit to the observations (chi2 = 3.21, df = 3, P = 0.38; RMSEA = 0.06; AGFI = 0.90; PGFI = 0.12). The range of Cronbach alpha and ICC for the scales was about 0.63 to 0.97 and 0.862 to 0.988, respectively. CONCLUSION: The findings of the present study provided an initial support for the reliability and validity of the HAPA-based PA inventory among patients with T2DM. PMID- 27386422 TI - An analysis of weight loss articles and advertisements in mainstream women's health and fitness magazines. AB - BACKGROUND: Magazines are a commonly used source for health and fitness information. Little is known about the nature and extent of weight loss strategies and products presented in mainstream women's health and fitness magazines. METHODS: This preliminary cross-sectional study evaluated the prevalence of articles and advertisements featuring weight loss content and products in mainstream US-based health and fitness magazines, as well as assessed weight loss themes presented. Thirty-one US health and fitness-focused magazine issues were coded. Prevalence of, product type, and themes related to weight loss in articles and advertisements were assessed. RESULTS: Among the 31 issues of the five US-based women's magazines examined, we identified 39 articles (4.8% [95% CI = 3.3% to 5.5%] of 819 articles) related to weight loss with 14 identified weight loss topics. The most prevalent article topics covered were exercising/workouts (32.0% [95% CI = 28.8% to 33.6%]) followed by dieting (18.6% [95% CI = 15.9% to 19.9%]).The most common product advertised was weight loss pills (46.0% [95% CI = 42.6% to 47.7%]). Fat burners were also frequently advertised (14.9% [95% CI = 12.5% to 16.1%]) followed by hunger reduction strategies (10.3% [95% CI = 8.2% to 11.3%]) and fat blockers (6.9% [95% CI= 5.2% to 7.8%]). CONCLUSION: Articles presented information about exercise and dieting whereas advertisements supported potentially harmful health beliefs and behaviors. As a well-utilized American media format, health and fitness-focused magazines have an opportunity to communicate frequent,accurate messaging about healthy weight reduction and limit advertisements that may include misleading claims. PMID- 27386423 TI - Response costs of mammography adherence: Iranian women's perceptions. AB - BACKGROUND: Mammography as the most common secondary prevention method has known to be helpful in detecting breast cancer at the early stages. Low level of participation among women toward mammography uptake due to cultural beliefs is a great concern. This study aimed at exploring the perceptions of women about response costs of mammography adherence (MA) in Yazd, Iran. METHODS: A qualitative study using semi-structured interviews was performed. Fourteen women,one oncology nurse, and a breast cancer survivor were purposefully interviewed. Interviews were transcribed verbatim and analyzed by directed content analysis method based on protection motivation theory (PMT). RESULTS: One main theme was emerged from the analysis namely called "response costs".Two main categories were also emerged from the data; (1) psychological barriers with six subcategories including "embarrassment," "worry about being diagnosed with cancer," "preoccupation with underlying disease," "misconception about mammography," "need for an accompanying person," and "internalizing the experiences of the others," and (2) maladaptive coping modes which encompassed three subcategories: "religious faith," "fatalism," and"avoidance and denial." CONCLUSION: Useful information was provided about the response costs of mammography utilization based on the perceptions of women. Cognitive barriers may be decreased by conducting modifications in women's awareness and attitude toward MA as well as changing the national health system infrastructures. Incorporating religious and cultural belief systems into MA educational programs through motivational messages is recommended. PMID- 27386424 TI - Media coverage of the Ebola virus disease in four widely circulated Nigerian newspapers: lessons from Nigeria. AB - BACKGROUND: The importance of the media in the coverage of Ebola virus disease (EVD) in Nigeria and its implications (negative or positive) amongst the populace cannot be overemphasized.This study was conducted to assess the role of media in the Ebola reportage and its implication in creating awareness and stopping the spread amongst the populace. METHODS: The nature and extent of media coverage about Ebola in four major national newspapers were examined. The four major national newspapers were The Sun, The Vanguard, The Nation and The Punch newspapers. The period of study ranged from 20 July (when the index case came to Nigeria) to 20 October 2014. Analysis of the newspaper article was according to content. RESULTS: A total of 1625 articles were published between July 2014 to October 2014 and these were divided into news (1127; 69.4%), features (267; 16.4%), opinion (76; 4.7%), editorials (149; 9.2%) and interviews (6; 0.4%). The most common topic was Ebola cases in Nigeria (17.5%) followed by discrimination due to Ebola (10.8%) and least of all the use of salt and or Kola for the cure of Ebola (5.2%). CONCLUSION: Although the World Health Organization (WHO) declared Nigeria Ebola free on the 20th October 2014, continual reportage of the Ebola disease for effective awareness, prevention and control of the virus is recommended. PMID- 27386425 TI - Assessment of operators' mental workload using physiological and subjective measures in cement, city traffic and power plant control centers. AB - BACKGROUND: The present study aimed to evaluate the operators' mental workload (MW) of cement, city traffic control and power plant control centers using subjective and objective measures during system vital parameters monitoring. METHODS: This cross-sectional study was conducted from June 2014 to February 2015 at the cement, city traffic control and power plant control centers. Electrocardiography and electroencephalography data were recorded from forty males during performing their daily working in resting, low mental workload (LMW), high mental workload (HMW) and recovery conditions (each block 5 minutes). The NASA-Task Load Index (TLX) was used to evaluate the subjective workload of the operators. RESULTS: The results showed that increasing MW had a significant effect on the operators subjective responses in two conditions ([1,53] = 216.303, P < 0.001, eta2 = 0.803). Also,the Task-MW interaction effect on operators subjective responses was significant (F [3, 53] = 12.628,P < 0.001, eta2 = 0.417). Analysis of repeated measures analysis of variance (ANOVA) indicated that increasing mental demands had a significant effect on heart rate, low frequency/high frequency ratio, theta and alpha band activity. CONCLUSION: The results suggested that when operators' mental demands especially in traffic control and power plant tasks increased, their mental fatigue and stress level increased and their mental health deteriorated. Therefore, it may be necessary to implement an ergonomic program or administrative control to manage mental probably health in these control centers. Furthermore, by evaluating MW, the control center director can organize the human resources for each MW condition to sustain the appropriate performance as well as improve system functions. PMID- 27386427 TI - Heterogeneity and Subclassification of Barcelona Clinic Liver Cancer Stage B. PMID- 27386426 TI - Domestic elder abuse in Yazd, Iran: a cross-sectional study. AB - BACKGROUND: Social changes due to urbanism, acculturation, and fading of values have led to some challenges in family relationships, including domestic elder abuse. This study was conducted to determine elder abuse status in Yazd, Iran. METHODS: This cross-sectional study was conducted on 250 elderly people over 60 years in Yazd in 2014-2015. Clustered random sampling was used to recruit the participants from 10 clusters in Yazd (25 individuals from each cluster). The data were gathered by the 49-item,Iranian Domestic Elder Abuse Questionnaire which was filled out through private interviews with the participants. RESULTS: Mean score of elder abuse was 11.84 (SD: 12.70) of total 100. Of the participants,79.6% (95% CI: 74.5-84.6) experienced at least one type of abuse. Emotional neglect was the most reported abuse and physical abuse was the least reported. Abuse score was associated with age, education level, living status, and insurance status of elders. Further, those who reported history of gastrointestinal problems, dyslipidemia, respiratory diseases, sleep disorders, audiovisual problems, joints pain, hypertension, dental/oral problems, cardiovascular disease,urinary incontinence and disability, reported a statistically significant higher abuse score. CONCLUSION: Despite overall low rate of domestic elder abuse, its high prevalence indicates that some interventions are necessary to decrease domestic elder abuse. Emotional neglect of elders should be addressed more than other abuse types. PMID- 27386428 TI - National Cancer Centre Singapore Consensus Guidelines for Hepatocellular Carcinoma. AB - Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world, but the second most common cause of cancer death. There is no universally accepted consensus practice guidelines for HCC owing to rapid developments in new treatment modalities, the heterogeneous epidemiology and clinical presentation of HCC worldwide. However, a number of regional and national guidelines currently exist which reflect practice relevant to the epidemiology and collective experience of the consensus group. In 2014, clinicians at the multidisciplinary Comprehensive Liver Cancer Clinic (CLCC) at the National Cancer Centre Singapore (NCCS) reviewed the latest published scientific data and existing international and regional practice guidelines, such as those of the National Comprehensive Cancer Network, American Association for the Study of Liver Diseases and the Asian Pacific Association for the Study of the Liver, and modified them to reflect local practice. These would serve as a template by which treatment outcomes can be collated and benchmarked against international data. The NCCS Consensus Guidelines for HCC have been successfully implemented in the CLCC since their publication online on 26(th) September 2014, and the guidelines allow outcomes of treatment to be compared to international data. These guidelines will be reviewed periodically to incorporate new data. PMID- 27386430 TI - Selection Criteria and Current Issues in Liver Transplantation for Hepatocellular Carcinoma. AB - Liver transplantation (LT) is an ideal treatment for hepatocellular carcinoma (HCC) because it not only resects HCCs but it also replaces the underlying damaged liver with normal tissue. However, the selection criteria are still a matter of debate. After the introduction of the Milan criteria, some expanded criteria focusing on tumor size and number have been proposed. In addition, new expanded criteria considering tumor biology have been proposed using tumor markers and (18)F-fluorodeoxyglucose positron emission tomography. This review summarizes the selection criteria in LT for HCC and introduces current issues focusing on the treatment for hepatitis C virus infection and the significance of sarcopenia in this field. PMID- 27386429 TI - Outcomes of Hepatic Resection in Intrahepatic Cholangiocarcinoma Patients with Diabetes, Hypertension, and Dyslipidemia: Significance of Routine Follow-Up. AB - BACKGROUND: The outcomes of hepatic resection in intrahepatic cholangiocarcinoma (ICC) patients with diabetes mellitus (DM), hypertension (HT), and dyslipidemia (DL) (metabolic components) remain unclear. METHODS: The outcomes of 43 ICC patients without known risk factors for ICC who underwent hepatic resection were retrospectively reviewed. These patients were divided into three groups: those followed-up for metabolic components at least every 6 months (follow-up group, n=16), those not followed-up for metabolic components (no follow-up group, n=14), and those without metabolic components (control group, n=13). RESULTS: In the follow-up group, 13 (81%) patients were further examined for ICC during follow-up because of abnormal screening results, such as elevated serum gamma-glutamyl transpeptidase and carbohydrate antigen 19-9 (CA19-9) concentrations or detection of hepatic tumor on ultrasonography and/or computed tomography, whereas most patients in the other two groups exhibited ICC-related symptoms. No patient in the follow-up group exhibited lymph node metastasis, whereas 43% of those in the no follow-up group and 46% in the control group had lymph node metastasis (p=0.005 and 0.004 vs. the follow-up group, respectively). All 16 patients in the follow-up group were diagnosed as International Union Against Cancer pathologic stage I or II (early stage). There were no significant differences in the incidence of postoperative recurrence between the three groups; however, the incidence of extrahepatic recurrence was lower in the follow-up group than in the no follow-up group and the control group (13% vs. 78% vs. 63%, p=0.0232). The 1-, 3-, and 5-year overall survivalrates in the follow-up group were better than those in the no follow-up and control groups (93/93/66% vs. 77/34/34% and 85/24/0%, p=0.034 and 0.001, respectively). CONCLUSIONS: Routine measurement of serum gamma-glutamyl transpeptidase and/or CA19-9 levels and imaging examinations every 12 months (or 6 months, if possible) are recommended during follow-up for DM, HT, and DL to detect ICC at an early stage. PMID- 27386431 TI - Tumor Heterogeneity in Hepatocellular Carcinoma: Facing the Challenges. AB - Tumor heterogeneity in hepatocellular carcinoma (HCC), such as that found in second primary tumors after curative treatment, synchronous multifocal tumors of different clonality, or intratumor heterogeneity, poses severe challenges for the development and administration of systemic molecular targeted therapies. Various methodologies, including historical DNA ploidy analysis, integrated hepatitis B virus DNA analysis, DNA fingerprinting, and next-generation sequencing technologies, are used to explore tumor heterogeneity in HCC. It is estimated that 30%-60% of recurrent or metastatic tumors harbor clones different from the primary tumor, 22%-79% of synchronous tumors vary clonally, and 12%-66% of single tumors contain intratumor heterogeneity. Substantial intertumor and intratumor heterogeneity renders biomarker identification, which is critical for the development and administration of molecular targeted therapy, challenging when applied to a single tumor biopsy specimen. The use of circulating tumor cells or circulating tumor DNA to evaluate overall tumor heterogeneity may help resolve this problem. This article reviews previous studies of tumor heterogeneity and discusses the implications and future opportunities regarding tumor heterogeneity in HCC. PMID- 27386433 TI - Impact of ATM and SLC22A1 Polymorphisms on Therapeutic Response to Metformin in Iranian Diabetic Patients. AB - Metabolic syndrome and its pathological sequel, type 2 diabetes are considered as important global health problems. Metformin is the most common drug prescribed for patients with this disorder. Consequently, understanding the genetic pathways involved in pharmacokinetics and pharmacodynamics of this drug can have a considerable effect on the personalized treatment of type 2 diabetes. In this study, we evaluated the association between rs11212617 polymorphism of ATM gene and rs628031 of SLC22A1 gene with response to treatment in newly diagnosed type 2 diabetes patients. We genotyped rs11212617 and rs628031 polymorphism by PCR based restriction fragment length polymorphism (RFLP) and assessed the role of this polymorphisms on response to treatment in 140 patients who have been recently diagnosed with type 2 diabetes and were under monotherapy with metformin for 6 months. Response to metformin was defined by HbA1c and fasting blood sugar (FBS) values. Based on such evaluations, patients were divided into two groups: responders (n= 63) and non-responders (n= 77). No significant association was found between these polymorphisms and response to treatment (OR= 0.86, [95% CI 0.52-1.41], P= 0.32) for rs11212617 and (OR= 0.45, [95% CI 0.64-1.76], P= 0.45) for rs 628031. The reported gene variants in ATM and SLC22A1 are not significantly associated with metformin treatment response in type 2 diabetic patients in an Iranian population. PMID- 27386434 TI - Zinc Finger 259 Gene Polymorphism rs964184 is Associated with Serum Triglyceride Levels and Metabolic Syndrome. AB - Metabolic syndrome (MetS) is characterized by a cluster of cardiovascular risk factors that include: abdominal obesity, dyslipidaemia, hypertension, insulin resistance and impaired glucose tolerance. Recent genome wide association studies have identified several susceptibility regions involved in lipid metabolism that are also associated with MetS. We have explored the association of 9 genetic polymorphisms involved in lipid metabolism and hypertension, including: MTHFR C677T, SELE L554F, FGB - 455G>A, GNB3 C825T, ZNF259 C>G, PSRC-1 A>G, CETP I405V, LPL S447X and LPA C>T in 97 subjects with MetS and 96 individuals without MetS who were recruited randomly from Mashhad stroke and heart atherosclerotic disorder (MASHAD) study using a stratified cluster random sampling technique. Anthropometric parameters and biochemical measurements were determined in all the subjects. Genotyping was carried out followed by univariate and multivariate analyses. The subjects with MetS had a higher triglyceride and lower HDL- C. CG+ GG genotypes of ZNF259 polymorphism (rs964184 C>G) and TT+CT genotypes of MTHFR C677T (rs1801133) were associated with MetS, and individuals carrying the G allele for ZNF259 or the T allele for MTHFR polymorphisms were associated with MetS (e.g, odds ratio (OR) for CG+GG genotypes vs. CC wild type: 2.52, CI=1.33 4.77; P=0.005). However, after multiple comparison adjustment, this relationship remained significant only for CG+ GG genotypes of ZNF259 polymorphism. Moreover, the ZNF259 CG+ GG genotypes were associated with increased serum concentrations of triglycerides and LDL-C, compared to the wild type. These data support the necessity for further studies in larger multicenter settings. PMID- 27386432 TI - Optimal Selection of Radiotherapy as Part of a Multimodal Approach for Hepatocellular Carcinoma. AB - A multimodal approach to treatment is a basic oncologic principle with proven survival benefits for most cancer types. However, existing guidelines recommend single modalities for treating each stage of hepatocellular carcinoma (HCC). Nonetheless, multimodal approaches can be considered for HCC, depending on the characteristics of the disease in individual cases. Radiotherapy (RT), an effective local modality, is a critical element of most multimodal approaches. Improved RTtechnology and increased understanding of the tolerance of the liver to radiation have contributed to the popularity of RT for treating liver tumors in clinical practice. Consequently, numerous reports have described the effects of RT on liver cancer, despite a lack of stringent evidence for its benefits. RT can be delivered using various technologies and approaches, which may be the source of some confusion. For example, high-dose ablative RT can be curative on its own, or high-dose ablative or conventional RT can complement other treatments such as radiofrequency ablation and transarterial chemoembolization. Combinations of systemic agents and RT can also be applied. This review discusses the optimal selection of RT as part of a multimodal approach for HCC. PMID- 27386435 TI - The Genotoxic and Cytotoxic Effects of Bisphenol-A (BPA) in MCF-7 Cell Line and Amniocytes. AB - Bisphenol-A (BPA) is an industrial xenoestrogen used widely in our living environment. Recently, several studies suggested that BPA has destructive effects on DNA and chromosomes in normal body cells via estrogen receptors (ER). Therefore, BPA could be considered as an important mediator in many diseases such as cancer. However, there are still many controversial issues which need clarification. In this study, we investigated the BPA-induced chromosomal damages in MCF-7 cell line, ER-positive and negative amniocyte cells. Cytotoxicity and genotoxicity effects of BPA were also compared between these three cell groups. Expression of estrogen receptors was determined using immunocytochemistry technique. The cell cytotoxicity of BPA was measured by MTT assay. Classic cytogenetic technique was carried out for the investigation of chromosome damage. BPA, in addition to cytotoxicity, had remarkable genotoxicity at concentrations close to the traceable levels in tissues or biological fluids. Although some differences were observed in the amount of damages between ER-positive and negative fetal cells, interestingly, these differences were not significant. The present study showed that BPA could lead to chromosomal aberrations in both ER dependent and independent pathways at some concentrations or in cell types yet not reported. Also, BPA could probably be considered as a facilitator for some predisposed cells to be cancerous by raising the chromosome instability levels. Finally, estrogen receptor seems to have a different role in cytotoxicity and genotoxicity effects. PMID- 27386436 TI - A Pilot Study of CK19, CK20 and GCC mRNA in the Peripheral Blood as a Colorectal Cancer Biomarker Panel. AB - Colorectal cancer remains one of the major cancer- related deaths despite progress in the treatment during past decades. Detection of disease at earlier stages reduces its mortality. The aim of current study was to investigate expression of Cytokeratin 19 (CK19), Cytokeratin 20 (CK20) and Guanylyl Cyclase C (GCC) mRNA in peripheral blood of non- metastatic colorectal cancer patients which may result into introducing of an early detection test. 25 patients with colorectal cancer and 25 healthy controls were recruited. Blood was obtained from all individuals. Expression of CK19 and CK20 and GCC mRNA and 18SrRNA (as reference gene) were determined based on real- time RT-PCR on total RNA from blood. CK19, CK20 and GCC expression had been detected in 68%, 76% & 52% of patient group, respectively, which was higher than healthy group, with 8%, 32% and 0% expression, respectively (p<0.05). CK20 was over-expressed 8- fold more in patients compared to controls. Similar result was found for CK19 with 4- fold over- expression. Sensitivity and specificity of combination of markers were 88% and 68%, respectively. Current data suggest that the detection of CK20 & CK19 as relative sensitive markers may become a valuable tool for primary diagnosis of colorectal cancer in early stages. GCC could be considered as a specific tumor marker for detection of colorectal cancer. Higher expression of these markers in patients may be considered as a relative good tool for the diagnosis of disease in non- metastatic stages. PMID- 27386437 TI - High Yield Overexpression, Refolding, Purification and Characterization of Pseudomonas aeruginosa Type B-Flagellin: An Improved Method Without Sonication. AB - Pseudomonas aeruginosa as an opportunistic pathogen is a significant cause of acute and chronic infections in patients with compromised defenses. This bacterium is motile via a single polar flagellum made of polymerized flagellin subunits differentiated into two major serotypes: A and B. flagellin plays an important role as a virulence factor in the adhesion, colonization and invasion of P. aeruginosa into host epithelial cells. To develop a functional vaccine that can be used in practical application to prevent and treat infection, type B flagellin was produced as recombinant protein. In this work, the fliC gene was introduced into a pET28a vector and expressed in Escherichia coli BL21 (DE3). The expressed recombinant protein was purified by a modified method without sonication using a HisTrap affinity column. The functional activities of produced flagellin were confirmed by ELISA, western blot analysis, motility inhibition assay and opsonophagocytosis test. The purification process of the type B flagellin was lead to a high yield. The produced recombinant type B-flagellin showed high biological activity in all of these standard assays. In conclusions, this report provides the new protocol to efficiently obtain the type B-flagellin with high biological activity and immunogenicity. This immunogen can be introduced as an adjuvant or vaccine in the future study. PMID- 27386438 TI - Orosomucoid-1 Expression in Ameloblastoma Variants. AB - Odontogenic tumors constitute a group of heterogeneous lesions of benign and malignant neoplasms with variable aggressiveness. Ameloblastomas are a group of benign but locally invasive neoplasms that occur in the jaws and are derived from epithelial elements of the tooth-forming apparatus. We previously described orosomucoid-1 protein expression in odontogenic myxomas. However, whether orosomucoid-1 is expressed in other odontogenic tumors remains unknown. Since orosomucoid-1 belongs to a group of acute-phase proteins and has many functions in health and disease, we identified and analyzed orosomucoid-1 expression in ameloblastoma variants and ameloblastic carcinoma using western blot and immunohistochemical techniques. Thirty cases of ameloblastoma were analyzed for orsomucoid-1; five specimens were fresh for western blot study (four benign ameloblastomas and one ameloblastic carcinoma), and 25 cases of benign ameloblastoma for immunohistochemical assays. Orosomucoid-1 was widely expressed in each tumor variant analyzed in this study, and differential orosomucoid-1 expression was observed between benign and malignant tumor. Orosomucoid-1 may play an important role in the behavior of ameloblastomas and influence the biology and development of the variants of this tumor. PMID- 27386440 TI - Return to sport after injuries: no answer to the main question. PMID- 27386439 TI - Practice of Consanguinity and Unusual Cases of Inherited Familial Chromosome Abnormalities: A Case Report. AB - We present 2 cases of likely rare event. In case 1, 3(rd) degree consanguineous marriage revealed inv(6) with same break points in parents who were found to be phenotypically normal. The same inv(6) being inherited in progeny but presented with low AMH (anti Mullerian hormone) and high level of FSH (follicular stimulating hormone) leading to polycystic ovarian syndrome/premature ovarian failure. In case 2, a couple was presented with 2(nd) degree consanguineous marriage and referred for 2 recurrent/ missed abortions. The amounts of shared genes are suggestive of more lethal genetic outcomes and inferred endogamy is a major driver to reproductive fiascoes, the ancestries of which are deeply tied at the meiotic level. PMID- 27386441 TI - Opening-wedge high tibial osteotomy: a seven - to twelve-year study. AB - PURPOSE: medial opening-wedge osteotomy is a widely performed procedure used to treat moderate isolated medial knee osteoarthritis. Historically, the literature has contained reports showing satisfactory mid-term results when accurate patient selection and precise surgical techniques were applied. This study was conducted to investigate the clinical and radiographic seven- to twelve-year results of opening-wedge high tibial osteotomy in a consecutive series of patients affected by varus knee malalignment with isolated medial compartment degenerative joint disease. METHODS: we reviewed a case series of 147 medial opening-wedge high tibial osteotomies at an average follow-up of 9.5 years. Endpoints for evaluation included the reporting of adverse effects, radiographic evidence of bone union, radiographic changes in the correction angle during union, and clinical and functional final outcomes. RESULTS: good or excellent results were obtained in 94% of the cases: the patients reported no major complications related to the opening-wedge high tibial osteotomy surgical technique, bone graft resorption, implant choice or postoperative rehabilitation protocol. At final follow-up, the average hip-knee angle was 4 degrees of valgus without major loss of correction during the healing process. A statistically significant change in the patellar height was detected postoperatively, with a trend towards patella infera. CONCLUSIONS: medial opening-wedge high tibial osteotomy is still a reliable method for correcting varus deformity while producing stable fixation, thus allowing satisfactory stability, adequate bone healing and satisfactory mid- to long-term results. LEVEL OF EVIDENCE: Level IV, therapeutic cases series. PMID- 27386442 TI - The influence of graft placement on clinical outcome in anterior cruciate ligament reconstruction. AB - PURPOSE: the aim of the present study was to investigate the influence of graft tunnel position on both clinical outcome and instrumental knee stability in patients submitted to arthroscopic ACL reconstruction using a bone-patellar tendon-bone (BPTB) graft. METHODS: thirty patients (24 men and 6 women) who underwent ACL reconstruction performed using an autologous bone-patellar tendon bone graft were studied at a mean follow-up of 18 months. Clinical outcome was assessed on the basis of the Lysholm score, Tegner activity level, International Knee Documentation Committee (IKDC) subjective form and the Short Form-36. Clinical outcomes were correlated with both femoral and tibial tunnel placement measured on standard anteroposterior and lateral knee radiographs, in accordance with established guidelines. RESULTS: tibial tunnel position on the lateral view correlated significantly with both the IKDC subjective form (r = -0.72; p<0.05) and the Lysholm score (r=-0.73; p<0.05). Tibial tunnel position on the lateral view also correlated with stability measured using a KT-1000 arthrometer at 30N of force (r=0.57; p<0.05). No correlation was found between alpha angle and anteroposterior (AP) laxity measured by KT-1000 arthrometer. No significant correlation was found between femoral tunnel position (on either view) and Lysholm score, IKDC score and Tegner activity level. Similarly, no correlation was found between AP laxity measured by KT-1000 arthrometer and femoral tunnel position. CONCLUSIONS: these results suggest that the more anterior the placement of the tibial tunnel, the better the clinical outcome will be. On the basis of literature data and our findings, we discuss the hypothesis that there exists a "correct area" for tunnel placement, making it possible to obtain the best results. LEVEL OF EVIDENCE: Level IV, case series. PMID- 27386444 TI - Failed vascularized fibular graft in treatment of osteonecrosis of the femoral head. A histopathological analysis. AB - PURPOSE: vascularized fibular grafting has been used to treat osteonecrosis of the femoral head in younger patients. Although the results described in the literature are promising, the failure rate is still significant, especially in steroid users. This study was undertaken to learn more, on a histopathological level, about the mechanism of vascularized fibular graft failure. METHODS: fifteen femoral heads removed at conversion to total hip arthroplasty were analyzed. The case load comprised 10 men and 5 women. They ranged in age from 28 to 39 years and had a median age of 35 years. The interval between the vascularized fibular implant procedure and the conversion to total hip arthroplasty ranged from 22 months to 30 months; the median interval was 26 months. All the patients were steroid users. The heads were sectioned and axial and coronal sections were taken and stained using the WHO method (hematoxylin, phloxine, saffron and Alcian green). A quantitative and qualitative analysis of graft-host interaction at the head (zone 1), neck (zone 2) and epiphysis (zone 3) was performed. RESULTS: all the specimens showed recognizable collapse of the articular surface over the area of necrosis. Thirteen femoral heads showed the presence of an osteochondral flap attached only at the margins of the area of avascular necrosis, and 10 of these 13 femoral heads also showed loss of the articulating surface with an ulcer crater corresponding to the exposed area of avascular necrosis. CONCLUSIONS: vascularized fibular graft failure seems to be related to a negative effect of creeping substitution: the revascularization becomes a negative force as it supports unbalanced bone resorption, which, as is well known, is enhanced by corticosteroids. CLINICAL RELEVANCE: creeping substitution is an undermining force in the repair and revascularization of the necrotic area in the femoral head. PMID- 27386443 TI - Platelet-rich plasma in the treatment of acute hamstring injuries in professional football players. AB - PURPOSE: muscle injuries have a high incidence in professional football and are responsible for the largest number of days lost from competition. Several in vitro studies have confirmed the positive role of platelet-rich plasma (PRP) in accelerating recovery and in promoting muscle regeneration, and not fibrosis, in the healing process. This study examines the results of intralesional administration of PRP in the treatment of primary hamstring injuries sustained by players belonging to a major league football club. METHODS: twenty-five hamstring injuries (grade 2 according to MRI classification) sustained by professional football players during a 31-months observation period were treated with PRP and analyzed. Sport participation absence (SPA), in days, was considered to correspond to the healing time, and we also considered the re-injury rate, and tissue healing on MRI. The mean follow-up was 36.6 months (range 22-42). RESULTS: there were no adverse events. The mean SPA for the treated muscle injuries was 36.76+/-19.02 days. The re-injury rate was 12%. Tissue healing, evaluated on MRI, was characterized by the presence of excellent repair tissue and a small scar. CONCLUSIONS: this study confirmed the safety of PRP in treating hamstring lesions in a large series of professional football players. PRP-treated lesions did not heal more quickly than untreated lesions described in the literature, but they showed a smaller scar and excellent repair tissue. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 27386445 TI - Coracoid syndrome: a neglected cause of anterior shoulder pain. AB - PURPOSE: the present prospective open-label study was designed to gain further insights into a condition thought to constitute a neglected but not uncommon syndrome characterized by anterior shoulder pain and tenderness to palpation over the apex of the coracoid process, not related to rotator cuff or pectoralis minor tendinopathy, long head of the biceps tendon disorders, or instability. The aim was to clarify its prevalence, clinical characteristics, differential diagnosis and response to corticosteroid injections. METHODS: patients with primary anterior shoulder pain precisely reproduced by deep pressure on the apex of the coracoid process were recruited. Patients with clinical or instrumental signs of other shoulder disorders were excluded. Patients were given an injection of triamcinolone acetonide 40 mg/ml 1 ml at the coracoid trigger point. They were evaluated after 15, 30 and 60 days and at 2 years using Equal Visual Analog Scale (EQ-VAS) and the Italian version of the Simple Shoulder Test (SST). RESULTS: between January 1 and December 31 2010, we treated 15 patients aged 26-66 years. The majority were women (86.67%). At 15 days, 6 (40%) patients reported complete resolution of their symptoms, while 9 (60%) complained of residual symptoms and received another injection. At 30 days, 14 (93.33%) patients were pain-free and very satisfied. At 2 years, the 14 patients who had been asymptomatic at 30 days reported that they had experienced no further pain or impaired shoulder function. The analysis of variance for repeated measures showed a significant effect of time on EQ-VAS and SST scores. CONCLUSIONS: the present study documents the existence, and characteristics, of a "coracoid syndrome" characterized by anterior shoulder pain and tenderness to palpation over the apex of the coracoid process and showed that the pain is usually amenable to steroid treatment. This syndrome should be clearly distinguished from anterior shoulder pain due to other causes, in order to avoid inappropriate conservative or surgical treatment. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 27386446 TI - An update on the grading of muscle injuries: a narrative review from clinical to comprehensive systems. AB - Muscle injuries are recognized to be among the most frequent injuries occurring in the sporting and athletic population, and they account for more than 30% of all injuries in professional soccer players. Despite their considerable frequency and impact, there is still a lack of uniformity in the categorization, description and grading of muscle injuries. Dozens of systems based on clinical signs, ultrasound imaging (US) appearance or magnetic resonance imaging (MRI) findings have been proposed over the years. Most of them are three-grade systems that take into account pain, ROM limitation, swelling and hematoma, hypoechoic or hyperintense areas on US or MRI, and muscle gap or tendon involvement; however, they still lack evidence-based prognostic value. Recently, new comprehensive classification systems have been proposed, with the aim of developing uniform muscle injury terminology and giving each severity grade prognostic value. The systems that combine detailed MRI and US features with the clinical presentation, such as the Munich Muscle Injury Classification, the ISMuLT classification, and the British Athletic Classification, if used extensively, could improve the diagnosis, prognosis and management of muscle injuries. PMID- 27386447 TI - Acute patellofemoral instability in children and adolescents. AB - Patellofemoral problems are considered to be among the most frequent causes of knee pain in children and adolescents. Correcting bone abnormalities through specific and targeted interventions is mandatory in skeletally immature patients. Medial patellofemoral ligament (MPFL) reconstruction is the preferred procedure, but there are several important precautionary considerations that the surgeon must take into account. It must always be remembered that MPFL rupture is the result, not the cause, of an altered extensor mechanism; therefore, patellar stabilization with MPFL reconstruction is only the first step to be accomplished in the management of an MPFL rupture. If other anatomical alterations are encountered, alternative/additional surgical procedures should be considered. If MPFL rupture occurs without associated anatomical or functional knee alterations, an appropriate rehabilitation program after MPFL reconstruction should be sufficient to achieve a good outcome. In conclusion, an acute patellar dislocation should be managed conservatively unless there is evidence of osteochondral damage or medial retinaculum lesions. Osseous procedures are contraindicated in children, while MPFL anatomical reconstruction with "physeal sparing" is the primary surgical option. PMID- 27386449 TI - Two cases of chronic knee pain caused by unusual injuries to the popliteus tendon. AB - Injuries to the popliteus tendon are less frequent than injuries to the menisci or ligamentous structures of the knee. When they do occur, injuries to the popliteus tendon tend to be the result of trauma and associated with injuries to other components of the knee. The most commonly seen injuries include tears at the musculotendinous junction and avulsion tears at the lateral femoral condyle insertion site. This report presents two unusual injuries of the popliteus tendon in patients with chronic knee pain: an isolated split tear of the tendon and a subluxed tendon residing within the lateral joint space. PMID- 27386450 TI - Current Understandings of Spontaneous Isolated Superior Mesenteric Artery Dissection. AB - Spontaneous isolated superior mesenteric artery dissection (SISMAD) has been known as a rare vascular disease. However it is increasingly reported in these days with the development of advanced imaging technology. Underlying etiology, natural course or an optimal management strategy of SISMAD is not exactly known at the moment. During the past 10 years, we have had an interest in this rare vascular disease and collected clinical and image data in 100 or more patients with SISMAD. In this review article, I would like to describe my current understanding of SISMAD on the base of our recent publications in the major vascular surgery journals. PMID- 27386448 TI - Outcome evaluation after Achilles tendon ruptures. A review of the literature. AB - The optimal treatment and the best rehabilitation protocol after an acute Achilles tendon rupture (ATR) remain a matter of controversy in orthopaedic and sports medicine. The use of validated injury-specific outcome instruments is the only way to clarify these issues, in order to ensure that patients receive the best possible treatment. This article describes the most commonly reported outcome measures used to assess patients treated for ATR. On the basis of the available evidence, the Achilles tendon Total Rupture Score (ATRS) is the most appropriate outcome measure for evaluating the management of acute ATR. PMID- 27386451 TI - Risk Factor Analysis for Buttock Claudication after Internal Iliac Artery Embolization with Endovascular Aortic Aneurysm Repair. AB - PURPOSE: Endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs) involving the common iliac artery requires extension of the stent-graft limb into the external iliac artery. For this procedure, internal iliac artery (IIA) embolization is performed to prevent type II endoleak. In this study, we investigated the frequency and risk factor of buttock claudication (BC) in patients having interventional embolization of the IIA. MATERIALS AND METHODS: From January 2010 to December 2013, a total of 110 patients with AAA were treated with EVAR in our institution. This study included 27 patients (24.5%) who had undergone unilateral IIA coil embolization with EVAR. We examined hospital charts retrospectively and interviewed by telephone for the occurrence of BC. RESULTS: Mean age of total patients was 71.9+/-7.0 years and 88.9% were males. During a mean follow-up of 8.65+/-9.04 months, the incidence of BC was 40.7% (11 of 27 patients). In 8 patients with claudication, the symptoms had resolved within 1 month of IIA embolization, but the symptoms persisted for more than 6 months in the remaining 3 patients. In univariate and multivariate analysis, risk factors such as age, sex, comorbidity, patency of collateral arteries, and anatomical characteristics of AAA were not significantly related with BC. CONCLUSION: In this study, BC was a frequent complication of IIA embolization during EVAR and there was no associated risk factor. Certain principles such as checking preoperative angiogram, proximal and unilateral IIA embolization may have contributed to reducing the incidence of BC. PMID- 27386452 TI - Upper Arm Basilic Vein Transposition for Hemodialysis: A Single Center Study for 300 Cases. AB - PURPOSE: The population of end-stage renal failure patients dependent on hemodialysis continues to expand with an increasing number of patients having an unsuitable cephalic vein or failed radio- and brachio-cephalic fistula. In these patients, the transposed basilic vein to brachial artery arteriovenous fistula (BaVT) provides autologous choice for hemodialysis. The results of basilic vein transposition arteriovenous fistula were assessed. MATERIALS AND METHODS: Three hundred cases of BaVT performed at a single center during the period of January 2005 to December 2011 were reviewed retrospectively. Data including demographics and postoperative complications were collected. Primary and secondary patency rates were determined by using Kaplan-Meier methods. RESULTS: The median age of patients was 57.4+/-13.1 years, and 154 patients were male. Renal failure was associated with hypertension in 88.7%, and with diabetes in 34.0%. The mean follow-up was 27.4+/-20.0 (12 to 72) months. There was no operation-related death. Eighteen patients required prosthetic graft interposition because of short vein. Thirty-five postoperative complications developed in 41 patients (148 cases), including thrombosis, stenosis, hematoma, seroma, arm swelling, steal syndrome, infection and aneurysm formation. Primary patency of BaVT was 69%, 60%, 53%, 52%, 44%, and 22% at 1, 2, 3, 4, 5, and 6 years, respectively. Secondary patency was 99%, 97%, 97%, 97%, 95%, and 95%, respectively. CONCLUSION: Chronic renal failure patients with hemodialysis may benefit from BaVT, because of high patency, less radiologic procedure, and less infection rate. The BaVT fistula should be used in preference to polytetrafluoroethylene grafts for secondary access. PMID- 27386453 TI - Aortobifemoral Reconstruction with Right Extra-Anatomic Obturator Foramen Bypass due to a Septic Groin. AB - The aortic bifurcation and iliac vessels are common sites of atherosclerotic occlusive disease causing the clinical expression known as "Leriche's syndrome". An aortobifemoral bypass grafting in the setting of a septic groin remains a significant challenge to vascular surgeons. We present a 65-year-old male with complete occlusion of the distal aorta and iliac arteries; he had undergone a left axillo-femoral and femoral-femoral artery bypass 2 years prior to our evaluation. Owing to a complex graft infection in the right groin and worsening lower extremity ischemia, we performed an aortobifemoral reconstruction through the right obturator membrane. This report highlights the safety and efficacy of the obturator bypass for avoiding infected groins while preserving vascular continuity and durability with 78 months of secondary patency rate. PMID- 27386454 TI - Left Subclavian Artery Occlusion: Femoro-Axillary Artery Retrograde Bypass. AB - The treatment tactics for subclavian artery occlusion include the more commonly used endovascular therapy rather than surgical intervention. We present a case of a 61-year-old woman with dialysis-dependent chronic renal failure who experienced left finger necrosis in the left upper extremity. To salvage the limb, we performed femoro-axillary (fem-ax) artery bypass using an autologous saphenous vein graft. However, 10 months later, she experienced coldness in the left forearm. Angiography revealed chronic total occlusion of the venous bypass. Despite emergent thrombectomy, redo fem-ax artery bypass operation was performed using a prosthetic graft. Upper limb salvage can be achieved by fem-ax artery retrograde bypass. PMID- 27386455 TI - Recurrent Arterial Thrombosis as a Presenting Feature of a Variant M3-Acute Promyelocytic Leukemia. AB - Acute limb ischemia (ALI) is a common vascular emergency. Hematologic malignancies are commonly associated with derangement of normal hemostasis and thrombo-hemorrhagic symptoms during the course of the disease are common. However, ALI as an initial presenting feature of acute leukemia is rare. Due to the rarity of this presentation, there is a scarcity of prospective randomized data to optimally guide the management of these patients. Current knowledge is mainly based on isolated cases. We report our experience managing a patient who presented with ALI and was found to have occult leukemia. A review of all cases with ALI as a presenting feature of acute leukemia is also presented. PMID- 27386456 TI - Delayed Presentation of Endovenous Heat-Induced Thrombosis Treated by Thrombolysis and Subsequent Open Thrombectomy. AB - Although endovenous heat-induced thrombosis (EHIT) is frequently reported after endovenous laser ablation (EVLA), the incidence and timing of occurrence of EHIT are not fully understood. We present a case of EHIT successfully treated with a combination of surgical and endovascular treatments. A 57-year-old woman, two months post bilateral EVLA, presented with a swollen leg. Deep vein thrombosis was diagnosed by Doppler ultrasonography and computerized tomographic venography. We treated the patient with catheter-directed thrombolysis with urokinase after insertion of an inferior vena cava filter. After thrombolytic treatment, we performed surgical venous thrombectomy, due to the presence of a large thrombus in the femoral vein. During the operation, we found organized old thrombus at the great saphenous vein which connected to the deep femoral vein. From these findings, we confirmed the presence of EHIT despite a long time having passed after EVLA. The patient was placed on anticoagulation therapy with oral rivaroxaban for three months. PMID- 27386457 TI - Double Nail of the Little Toe. AB - A rudimentary accessory or double nail of the little toe is not rare, although only described three times before. Most cases are accidentally detected and only few patients seek help because they have discomfort or pain. Some have a positive family history, but most patients cannot give any information concerning heredity. Clinically, the nail of the little toe is abnormally wide and is split or shows a longitudinal depression corresponding to a slight protuberance of the cuticle. Histopathology shows a complete though short nail. The treatment of choice is segmental excision of the entire accessory nail unit with mobilization of the lateral skin and primary suture. PMID- 27386458 TI - Erratum. AB - [This corrects the article DOI: 10.1159/000441569.]. PMID- 27386459 TI - Successful Treatment of Paecilomyces lilacinus Onychomycosis with Efinaconazole and Tavaborole. AB - Paecilomyces lilacinus, also known as Purpureocillium lilacinum, is a non dermatophyte mold found in the soil and used as nematocide for crops. P. lilacinus can cause rare opportunistic infections in humans ranging from endocarditis, keratitis, to onychomycosis with significant resistance to conventional antifungals. There are only two cases of onychomycosis caused by P. lilacinus reported in the literature and none that were successfully treated. Here we present a case of successfully treated onychomycosis caused by P. lilacinus with efinaconazole and tavaborole in a patient who had failed treatment with oral fluconazole, itraconazole, terbinafine, and topical ciclopirox and naftifine. PMID- 27386460 TI - Use of Low-Cost Videomicroscopy versus Standard Videodermatoscopy in Trichoscopy: A Controlled, Blinded Noninferiority Trial. AB - Affordable (USD ~30) handheld USB digital microscopes, or videomicroscopes (VMs), that provide *10-200 magnification are available on the web for nonmedical uses such as in botany, entomology, microelectronics or, recently, for hair/scalp evaluation. The aim of this study was to compare the reliability of low-cost VMs versus standard, medically marketed videodermatoscopes (VDs) in trichoscopy. Twenty-five patients affected by different types of hair loss were enrolled in a controlled, blinded noninferiority trial. All patients underwent examination by two low-cost VMs as well as by standard VD in order to evaluate any variability in the detection of common trichoscopic features. At the end of the study, the two low-cost VMs enabled a correct identification of all hair shaft alterations; as regards follicular and/or perifollicular examination, black dots were easily recognized by both equipments, but other follicular features, such as yellow dots, white dots and perifollicular scales, were not always adequately visualized because of low color quality and/or reduced brightness and/or resolution. In conclusion, our study suggests that the potential accuracy of low-cost VMs in the evaluation of hair loss may have some pitfalls. Therefore, a low-cost VM should not be routinely used for reliable scalp trichoscopy, unless supported by individual controlled noninferiority trials. PMID- 27386461 TI - Periungual Pyogenic Granuloma: The Importance of the Medical History. AB - Pyogenic granuloma (PG) is a common, benign vascular proliferation that can arise on the skin or subcutaneous tissue. It is more frequent in the early decades of life, and the most common locations are the digits of both hands and feet. The most common cause of periungual PG is drug intake, but many other trigger factors have been described in the literature. Treatment should be chosen according to the cause. We describe 2 particular cases of periungual PG in which the clinical history has been fundamental. In the first case, there was an underlying hand eczema, and in the second case, a foreign body was present. PMID- 27386463 TI - Longitudinal 'Half-and-Half Nails' or True Leukonychia. PMID- 27386462 TI - Frontal Fibrosing Alopecia and Increased Scalp Sweating: Is Neurogenic Inflammation the Common Link? AB - Frontal fibrosing alopecia (FFA) is an uncommon scarring hair loss disorder that is characterized by a band-like recession of the frontal hair line with eyebrow hair loss. We present a series of patients with FFA and increased sweating predominantly localized to the scalp, and potential explanations for this association are discussed. We hypothesize that the reported increase in sweating seen in our patients may be in part related to the inflammatory process occurring locally within the skin, either inducing a local axonal sweating reflex or through direct modulation of sweat gland secretion by neuropeptides. PMID- 27386465 TI - Titanium Pigment and Yellow Nail Syndrome. PMID- 27386464 TI - Treatment of Seborrhoeic Dermatitis in Asia: A Consensus Guide. AB - Seborrhoeic dermatitis (SD) is common in Asia. Its prevalence is estimated to be 1-5% in adults. However, larger population-based studies into the epidemiology of SD in Asia are lacking, and the aetiology of SD may differ widely from Western countries and in different parts of Asia. In addition, clinically significant differences between Asian and Caucasian skin have been reported. There is a need to define standardized clinical diagnostic criteria and/or a grading system to help determine appropriate treatments for SD within Asia. With this in mind, experts from India, South Korea, Taiwan, Malaysia, Vietnam, Singapore, Thailand, the Philippines, Indonesia, and Italy convened to define the landscape of SD in Asia at a meeting held in Singapore. The consensus group developed a comprehensive algorithm to aid clinicians to recommend appropriate treatment of SD in both adults and children. In most cases, satisfactory therapeutic results can be accomplished with topical antifungal agents or topical corticosteroids. Non-steroidal anti-inflammatory agents with antifungal properties have been shown to be a viable option for both acute and maintenance therapy. PMID- 27386466 TI - The Postpartum Telogen Effluvium Fallacy. AB - INTRODUCTION: Postpartum telogen effluvium (PPTE) is a commonly described entity, but few studies deal with the real incidence and pathogenesis of this claimed common disease. OBJECTIVE: To analyze the objective data published and to define the real incidence of the so-called PPTE. METHOD: A retrospective review of the published data was conducted. RESULTS: No statistically significant data were found in any of the papers reviewed, which could support the conclusion that the amount of hair shedding between pregnant and postpartum women is different. CONCLUSION: PPTE is not a well-defined entity, and the exact incidence is unknown. From our literature review, we could state that the frequency of PPTE is so low and undefined that we dare say that PPTE does not exist. PMID- 27386467 TI - Giant Onychomatricoma of the Great Toenail: Case Report and Review Focusing on Less Common Variants. AB - Onychomatricoma is a rare benign fibroepithelial filamentous tumor originating from the nail matrix. It typically presents with the clinical tetrad of xanthonychia, pachyonychia, proximal splinter hemorrhages and increased transverse overcurvature of the nail plate. The giant variant can easily confuse the clinician due to its extensive nail dystrophy that can mask the characteristic features of this tumor. Benign (fibrokeratoma, ungual fibroma, onycholytic matricoma) and malignant entities (Bowen's disease, squamous cell carcinoma, onycholytic carcinoma) are mimics of the disease. Nail surgery can facilitate the diagnosis, which should always be confirmed by histology, as rare variants do exist. PMID- 27386468 TI - Onychomycosis and Onychomatricoma. AB - Nail dermoscopy is helpful in the differential diagnosis of nail disorders including onychomycosis and pigmented and nonpigmented nail tumors. We report two cases of onychomatricoma with concurrent onychomycosis of the same digit. In both cases, dermoscopy of the nail plate exhibited features of onychomatricoma, whereas dermoscopy of the distal free edge revealed features of onychomycosis. It is not uncommon for patients with onychomatricoma to develop coexisting onychomycosis, as channels created by the tumor render the nail plate susceptible to invasion by fungi. PMID- 27386469 TI - Dystrophy of the Great Toenail by Subungual Exostosis and Hyperostosis: Three Case Reports with Different Clinical Presentations. AB - Subungual exostoses and hyperostoses of the great toenail are a differential diagnosis of nail tumors. We present 3 cases of subungual exostosis/hyperostosis with secondary nail dystrophy: a 36- and a 37-year-old woman as well as an 8-year old boy. Two of the 3 patients suffered from pain. The 2 female patients presented with the classic dorsolateral firm protrusion, while the child presented with bilateral nail dystrophy with lateral wall hypertrophy. In this later case, a bony ridge was identified, which is an unusual subungual, nonprotruding type of exostosis. The hypertrophic lateral walls were removed by the Vandenbos technique. In the 2 former cases, complete excision of the bony lesions was performed with a proximal block. Healing by second intention was uneventful. PMID- 27386471 TI - Endoscopic ultrasound-guided pancreaticobiliary intervention in patients with surgically altered anatomy and inaccessible papillae: A review of current literature. AB - The management of pancreaticobiliary disease in patients with surgically altered anatomy is a growing problem for gastroenterologists today. Over the years, endoscopic ultrasound (EUS) has emerged as an important diagnostic and therapeutic modality in the treatment of pancreaticobiliary disease. Patient anatomy has become increasingly complex due to advances in surgical resection of pancreaticobiliary disease and EUS has emerged as the therapy of choice when endoscopic retrograde cholangiopancreatography failed cannulation or when the papilla is inaccessible such as in gastric obstruction or duodenal obstruction. The current article gives a comprehensive review of the current literature for EUS-guided intervention of the pancreaticobiliary tract in patients with altered surgical anatomy. PMID- 27386470 TI - European Federation of Societies for Ultrasound in Medicine and Biology guidelines 2015 on interventional endoscopic ultrasound. PMID- 27386473 TI - Comparing cost-effectiveness between endoscopic ultrasound and endoscopic retrograde cholangiopancreatography in diagnosis of common bile duct stone in patients with predefined risks: A study from a developing country. AB - BACKGROUND AND OBJECTIVES: Endoscopic ultrasound (EUS) achieves results comparable to endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of common bile duct (CBD) stone, but studies from the western have shown EUS to be less expensive in patients with intermediate risk for CBD stones. The aim of this study was to compare the costs of EUS and ERCP in the diagnosis of CBD stones in a developing country. MATERIALS AND METHODS: A prospective study was done with 141 patients with suspected CBD stones, categorized as having high or intermediate risk for CBD stone. All underwent EUS, and the high-risk patients had ERCP after the EUS. For intermediate-risk patients, an ERCP was done at the discretion of the attending physician. The CBD stone was confirmed by ERCP in patients who underwent both EUS and ERCP. Patients who received EUS only were followed up every 3 months for 1 year. The false negative rate in patients with EUS and ERCP was estimated in the clinical follow-up. RESULT: One hundred and forty-one patients (141: 83 females, 58 males) with a mean age +/- standard deviation (SD) of 55.71 +/-18.68 years were recruited. Ninety-four (94) patients underwent both EUS and ERCP. ERCP confirmed the diagnosis in 83 of 85 patients (97.6%) with CBD stone detected by EUS. Forty-seven (47) patients with a negative EUS and no ERCP done were symptom-free during the follow-up. The overall sensitivity, specificity, positive predictive value, and negative predictive value of EUS were 97.6%, 80%, 97.6%, and 80% respectively. An EUS-based strategy for high-risk patients was 15% more expensive than an ERCP-based strategy, but the EUS-based strategy reduced the cost to 37.78% less than the ERCP-based strategy in intermediate-risk patients. The EUS-based strategy was cost-saving when the CBD stone prevalence was less than 52.5%. CONCLUSION: EUS is safer and less costly than ERCP for CBD stone diagnosis in patients with intermediate risk. PMID- 27386472 TI - Endoscopic ultrasound-guided fine-needle aspiration skill acquisition of gastrointestinal submucosal tumor by trainee endoscopists: A pilot study. AB - BACKGROUND AND OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is an effective method for tissue diagnosis of gastrointestinal submucosal tumors (SMTs) that are difficult to diagnose by standard endoscopic biopsy. However, the learning curve, especially for gastrointestinal SMT, has not been sufficiently established. The aim of our study was to assess the skill acquisition and diagnostic accuracy of EUS-FNA for gastrointestinal SMT in trainee endoscopists in order to elucidate the optimal starting standards of EUS FNA. MATERIALS AND METHODS: We prospectively evaluated 51 EUS-FNA procedures for gastrointestinal SMT between May 2010 and March 2014. The procedure was performed by two trainee endoscopists and two expert endoscopists. We investigated the diagnostic yield of EUS-FNA and the factors associated with the accuracy between the trainee endoscopists and expert endoscopists. RESULTS: The rate of adequate EUS-FNA materials for histological examination was 86.3%. Although infections occurred in two cases (3.9%), which were managed conservatively, no severe complications were identified. Comparing the trainee endoscopists with expert endoscopists, there was no significant difference in the rate of gaining adequate specimen (76.5% vs. 82.3%, P = 0.4626). However, the mean number of passes of the trainees tended to be more than that of the expert endoscopists (2.1 pass vs. 1.7 pass, P = 0.0511), and lesions located in the middle third of the stomach were the predictive factors for nondiagnostic tumors by the trainee endoscopists (P = 0.0075). CONCLUSION: EUS-FNA for gastrointestinal SMT by trainee endoscopists can be safely performed under the supervision of EUS-FNA expert endoscopists. PMID- 27386474 TI - Evaluation of the diagnostic utility of endobronchial ultrasound-guided transbronchial needle aspiration for metastatic mediastinal tumors. AB - BACKGROUND AND OBJECTIVES: The mediastinum is a relatively uncommon site of distant metastases, which typically appear as peripheral lung nodules. We chose to assess the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the diagnosis of distant metastases to the mediastinum. MATERIALS AND METHODS: Over the period 2008-2013, a total of 446 patients with concurrent or previously diagnosed and treated extrathoracic malignancies were evaluated. RESULTS: Surgical treatment was carried out in 414 patients (156 women and 237 men aged 26-68 years, mean age of 56.5 years) presenting with distant metastases to the lungs: Thoracoscopic wedge resection was completed in 393 patients and lobectomy and segmentectomy were performed in 7 and 14 patients, respectively. The median time from primary tumor resection was 6.5 years (range: 4.5 months to 17 years). Thirty-two of these patients underwent EBUS-TBNA for mediastinal manifestation of the underlying disease. EBUS-TBNA specimens were aspirated from the subcarinal or right paratracheal lymph node stations in 26 (81%) patients and from the hilar lymph nodes in 6 (18.8%) patients only. Metastases to lymph nodes were confirmed in 14 of these patients (43.8%). Primary lung cancer was diagnosed in seven patients. Mediastinoscopy was performed in two patients to reveal either lymph node metastasis or sarcoidosis. Thoracotomy for pulmonary metastases resection and mediastinal lymph node biopsy was performed in nine patients. Lymph node metastasis was confirmed in five patients (15.6%). The diagnostic efficacy, sensitivity, specificity, and negative predictive value (NPV) of EBUS-TBNA were 78.8%, 93.3%, 100%, and 87.5%, respectively. CONCLUSION: EBUS-TBNA is a valuable diagnostic tool in a selected group of patients with secondary tumors in the mediastinum and lungs. PMID- 27386475 TI - Pathologic evaluation of a new endoscopic ultrasound needle designed to obtain core tissue samples: A pilot study. AB - BACKGROUND AND OBJECTIVES: Standard endoscopic ultrasound-fine-needle aspiration (EUS-FNA) needles are in widespread use. Meaningful differences between the available needles have been difficult to identify. Recently, a new EUS needle (Shark Core(r), Covidien, Dublin, Leinster, Ireland), has been introduced in an attempt to improve diagnostic accuracy, tissue yield, and to potentially obtain a core tissue sample. We performed a pilot study prospectively to evaluate this new needle when compared to a standard EUS-FNA needle. MATERIALS AND METHODS: Analysis of the first 15 patients undergoing EUS-FNA with the Shark Core needle was performed and it was compared to EUS-FNA in 15 patients who underwent EUS-FNA with a standard needle. RESULTS: The Shark Core needle required fewer needle passes to obtain diagnostic adequacy than the standard needle [(chi(2)(1) = 11.3, P < 0.001]. The Shark Core needle required 1.5 passes to reach adequacy, whereas the standard needle required three passes. For cases with cell blocks, the Shark Core needle produced diagnostic material in 85% of cases [95% confidence interval (CI): 54-98], whereas the standard needle produced diagnostic material in 38% of the cases (95% CI: 9-76). The Shark Core needle produced actual tissue cores 82% of the time (95% CI: 48-98) and the standard needle produced no tissue cores (95% CI: 0-71) (P = 0.03). CONCLUSION: This pilot study found that the Shark Core needle had a high rate of producing adequate cytologic material for the diagnosis of pancreatic and peri-pancreatic lesions sampled by EUS with fewer passes required to obtain a definitive diagnosis and with a high rate of tissue cores being obtained when compared to a standard FNA needle. PMID- 27386476 TI - Characteristic endoscopic ultrasound findings of ampullary lesions that predict the need for surgical excision or endoscopic ampullectomy. AB - BACKGROUND AND OBJECTIVES: The management of ampullary lesions has evolved to include endoscopic ampullectomy (EA) as a curative approach to cancers of the ampulla of Vater. With this change comes a need to risk-stratify patients at initial diagnosis. MATERIALS AND METHODS: Patients with verified ampullary lesions (N = 50) were analyzed in a case-control design. We evaluated endoscopic ultrasound (EUS) data to define characteristics that yield a high sensitivity in selecting candidates for EA. RESULTS: Using data from previously published studies yielded a sensitivity of 0.765 in appropriately identifying the 34 surgical cases. Expanding these characteristics increased the sensitivity of EUS to 0.971 in identifying surgical candidates. Additionally, of advanced disease cases, the expanded characteristics correctly identified these cases with a sensitivity of 1.0-improved over 0.708 using prior published data. CONCLUSION: EA should be strongly considered if ampullary lesions are found to fit the following characteristics after EUS evaluation: lesion size <2.5 cm, invasion <=4 mm, pancreatic duct dilatation <=3 mm, <=T1 lesion, no lymph nodes present, and no ductal stent in place. Furthermore, EUS data can be used to identify all high risk lesions. With these characteristics identified, clinicians are better able to risk-stratify patients using EUS as either appropriate for or too high-risk for endoscopic resection. PMID- 27386477 TI - Efficacy and safety of electromagnetic navigation bronchoscopy with or without radial endobronchial ultrasound for peripheral lung lesions. AB - BACKGROUND AND OBJECTIVES: Electromagnetic navigation bronchoscopy (ENB) is a promising new technology to increase the diagnostic yield of peripheral lung and mediastinal lesions. Conventional flexible bronchoscopy has a limited yield in peripheral pulmonary lesions, even in experienced hands. Radial endobronchial ultrasound (r-EBUS) with its real-time imaging capability can help to diagnose peripheral pulmonary lesions. In the present study, we aimed to investigate the diagnostic yield and safety of ENB with or without r-EBUS for peripheral lung lesions. MATERIALS AND METHODS: This study was conducted in a tertiary medical center, and 56 consecutive patients who were thought to be the best candidates for bronchoscopic biopsies at a multidisciplinary meeting were enrolled. ENB was performed under conscious sedation by using an electromagnetic tracking system with multiplanar reconstruction of previously acquired computed tomography (CT) data. Sampling was performed by biopsy forceps, endobronchial brush, and bronchoalveolar lavage. RESULTS: Fifty-six patients (50 men and 6 women; mean age, 60 +/- 9 years) were studied. While an electromagnetic navigation system was used in all patients, r-EBUS was used in 26 of 56 patients. The median diameter of the lesions was 30 mm (interquartile range: 23-44 mm). Mean distance of the lesions from the pleura was 14.9 +/- 14.6 mm. Mean procedure time was 20 +/- 11.5 min. Mean registration error was 5.8 +/- 1.5 mm. Mean navigation error was 1.2 +/ 0.5 mm. The diagnostic yield of the procedure was 71.4% for peripheral lesions (non-small cell lung cancer = 23, small cell lung cancer = 3, benign diseases = 14). Pneumothorax occurred in only 1 patient (1.7%). CONCLUSION: ENB with or without r-EBUS is a safe, efficient, and easily applied method for sampling of peripheral lung lesions, with high diagnostic yield independent of lesion size and location. PMID- 27386478 TI - Time-of-day effect and the yield of endoscopic ultrasound fine needle aspiration. AB - BACKGROUND AND OBJECTIVES: The timing of the endoscopic procedures has been recently proposed to be a factor in the quality of colonoscopic polyp detection. We aimed to investigate whether the time-of-day has an effect on the diagnostic yield and specimen adequacy of endoscopic ultrasound fine needle aspiration (EUS FNA). MATERIALS AND METHODS: The retrospective study was set in a safety net community hospital. The 212 EUS-FNAs performed at our institution between July 2011 and January 2014 were retrospectively analyzed. Pancreatic masses, pancreatic cysts, and lymphadenopathy were most common indications for EUS-FNAs. Data were collected with regard to the timing of the procedure, presence of on site cytopathologic evaluation, the number of needle passes, diagnosis, and specimen adequacy for cytopathologic evaluation. Statistical analysis was performed using unpaired two-tailed Student's t-test. RESULTS: There was no difference in the diagnostic yield for malignancy across all indications between the AM and PM groups. In the morning group 31/87 (36%) procedures and in the afternoon group 50/125 (40%) procedures were diagnostic for malignancy (P = 0.522). There was no difference in the specimen adequacy for cytopathologic evaluation across all indications between the AM and PM groups. In the morning group, 58/87 (67%) procedures and in the afternoon group 90/125 (72%) procedures were adequate for cytopathologic evaluation (P = 0.408). On-site cytopathologist was more available for AM than PM procedures; however, the lack of AM vs. PM difference in the yield and specimen adequacy persisted regardless of on-site cytopathologist presence. CONCLUSIONS: Time-of-day of the procedure (morning vs. afternoon) does not affect EUS-FNA diagnostic yield for malignancy or specimen adequacy for cytopathologic evaluation. PMID- 27386479 TI - Failed common bile duct cannulation during pregnancy: Rescue with endoscopic ultrasound guided rendezvous procedure. AB - Common bile duct (CBD) stones can lead to serious complications and require intervention with either endoscopic retrograde cholangiopancreatography (ERCP) or laparoscopic techniques for urgent relief. On an average 10%-20% of the patients with gall bladder stones can have associated CBD stones. CBD stones during pregnancy can be associated with hazardous complications for both the mother and the fetus. Failed cannulation while performing ERCP during pregnancy is a technically demanding situation, which requires immediate rescue with special techniques. Conventional rescue techniques may not be feasible and can be associated with hazardous consequences. Endoscopic ultrasound (EUS) guided rendezvous technique has now emerged as a safe alternative, and in one of our patients, this technique was successfully attempted. To the best of our knowledge, this is the first case report in the literature on EUS-guided rendezvous procedure during pregnancy. PMID- 27386480 TI - Thymic carcinoma diagnosed by using endoscopic ultrasound with fine-needle aspiration. AB - There is a paucity of literature on the use of endoscopic ultrasound (EUS) for evaluating superior mediastinal structures, especially the thymus gland. We report a case of thymic carcinoma diagnosed by using EUS elastography with strain ratio and fine-needle aspiration (FNA). A 64-year-old woman presented with altered mental status and was diagnosed with autoimmune encephalitis. Further work-up suggested a superior mediastinal mass, for which she underwent EUS. A hypoechoic mass was found in the superior mediastinum at the level of the aortic arch. Real-time EUS elastography showed a predominantly blue hue to the mass concerning for malignancy. FNA of the mass was performed, which revealed numerous large neoplastic cells under a background of a small lymphoid infiltrate. Immunohistochemistry was strongly positive for PAX8, pancytokeratin, and CAM5.2. The pathologic and immunohistochemical stains were consistent with thymic carcinoma. PMID- 27386481 TI - Disseminated lymphangiomatosis presenting as chylous ascites and diagnosed with endoscopic ultrasound. PMID- 27386482 TI - Endoscopic ultrasound elastography to diagnose sarcoidosis. PMID- 27386483 TI - Detection of HER2 polymorphism and expression using circulating DNA and RNA as a tool in lung adenocarcinoma patients: a case control study. AB - BACKGROUND: Circulating DNA and RNA is an important prognostic tool for noninvasive malignant disease detection and in disease prognosis. Study aimed to evaluate the possible prognostic role of HER2 (-3444C/T) promoter polymorphism and its mRNA expression in Lung adenocarcinoma patients using circulating DNA and RNA. METHODS: One hundred newly diagnosed lung adenocarcinoma patients and 100 age and sex matched healthy controls were included and allele specific (AS) polymerase chain reaction (PCR) was used for genotyping and expression was analyzed by quantitative real time PCR. Overall survival of patients was analyzed by Kaplan-Meier method. RESULTS: We observed a statistically significant difference in the frequency of HER2 CC, CT, and CT genotype among lung adenocarcinoma cases vs. healthy controls (P=0.001). Compared to the CC genotype, OR 2.51 (1.4-4.51), 5.97 (1.17-30.41) and RR 1.56 (1.17-2.07), 2.83 (0.82-9.73) for heterozygous CT and homozygous TT genotypes suggesting possible dominant effect on risk of lung adenocarcinoma. Cases with CC genotype showed 9.29 fold increased mRNA expression while cases with heterozygous CT and homozygous TT genotype showed 16.26, 16.72 fold increased mRNA expression (P<0.0001). We observed 13.92 fold increased HER2mRNA expression Lung adenocarcinoma patients. Patients in different TNM stages showed significant difference in HER2 mRNA expression which was found to be significantly associated (P<0.0001). Patients with distant metastases and without distant metastases had 17.44 and 11.16 fold increased HER2 mRNA expression was also found to be significantly associated (P<0.0001). It was also observed that patients with pleural effusion and without pleural effusion showed significant difference in HER2 mRNA expression (P=0.03). We also analysed patients with CC, TT, CT (P=0.02) and CT + TT (P=0.008) genotype showed 15.8, 7.9, 9.5 and 7.9 months of overall median survival time and found to be significantly associated, respectively. Patients with >13 and <=13 fold increased HER mRNA expression also showed 7.9 and 11.5 months of overall median survival time was also found to be significantly associated (P=0.01). CONCLUSIONS: Our work provides evidence that circulating DNA and RNA may be a potential prognostic tool in Lung adenocarcinoma patients. Promoter polymorphism of HER2 (-3444C/T) gene had significant impact on higher HER2 mRNA expression could be a predictive factor for patients' worse overall survival and metastatic behaviour. PMID- 27386484 TI - Plasma alkaline phosphatase and survival in diabetic patients with acute myocardial infarction. AB - BACKGROUND: Alkaline phosphatase (ALP) removes phosphate groups from many types of molecules. The aim of the present research was to study the relation between plasma ALP and survival in diabetic patients with myocardial infarction. METHODS: Retrospective study: from 954 admissions (15 months period) in a coronary care unit, we selected 200 admissions corresponding to 195 patients with myocardial infarction and diabetes mellitus. Survival after no less than 48 months, and up to 61 months, after the myocardial infarction episode, was under study, in association with ALP levels. RESULTS: A relatively weak but significant correlation was seen between the peak plasma cardiac troponin I and ALP levels (r: 0.21, significance level: 0.003). Using the median value for ALP as cut-off (74 IU/L), plasma creatinine was significantly higher in patients with higher values for ALP. Patients with elevated ALP had decreased survival in Kaplan-Meier analysis (significance level in log-rank test: 0.032). This finding was noted for male patients (significance level in log-rank test: 0.035), but not for female patients (significance level in log-rank test: 0.497). CONCLUSIONS: Elevated ALP acts as a prognostic indicator of decreased survival in diabetic patients with acute myocardial infarction, possibly in association to decreased renal function. This finding is limited to male patients, pointing to a possible different role for phosphatase activity in cardiovascular disease in male and female diabetic patients. PMID- 27386485 TI - Bioaerosols in the lungs of subjects with different ages-part 1: deposition modeling. AB - BACKGROUND: In this contribution the inhalation and deposition of bioaerosols including particles with various shapes and sizes were investigated for probands with different ages (1, 5, 15 and 20 y). The study should help to increase our knowledge with regard to the behavior of variably shaped and sized particles in lungs being subject to different developmental stages. METHODS: Simulation of particle transport and deposition in single structures of the respiratory tract was conducted by using a stochastic model of the tracheobronchial tree and well validated analytical and empirical deposition formulae. Possible effects of particle geometry on deposition were taken into consideration by application of the aerodynamic diameter concept. Age-dependent lung morphometry and breathing parameters were computed by using appropriate scaling factors. RESULTS: Theoretical simulations came to the result that bioparticle deposition in infants and children clearly differs from that in adolescents and adults insofar as the amount of deposited mass exhibits a positive correlation with age. Nose breathing results in higher extrathoracic deposition rates than mouth breathing and, as a consequence of that, lower particle amounts are enabled to enter the lung structures after passing the nasal airways. Under sitting breathing conditions highest alveolar deposition rates were calculated for particles adopting aerodynamic diameters of 10 nm and 4 um, respectively. CONCLUSIONS: The study comes to the conclusion that bioparticles have a lower chance to reach the alveoli in infants' and children's lungs, but show a higher alveolar deposition probability in the lungs of adolescents and adults. Despite of this circumstance also young subjects may increasingly suffer from biogenic particle burden, when they are subject to a long-term exposure to certain bioaerosols. PMID- 27386486 TI - Elevated d-dimer cut-off values for computed tomography pulmonary angiography-d dimer correlates with location of embolism. AB - BACKGROUND: Acute pulmonary embolism (APE) is a potentially fatal condition, and making a timely diagnosis can be challenging. Computed tomography pulmonary angiography (CTPA) has become the modality of choice, and this contributes to the increasing load on emergency room CT scanners. Our purpose was to investigate whether an elevated d-dimer cut-off could reduce the demand for CTPA while maintaining a high sensitivity and negative predictive value (NPV). METHODS: We retrospectively reviewed all patients referred for CTPA with suspicion of APE in 2012, and collected d-dimer values and CTPA results. We investigated the diagnostic performance of d-dimer using a 0.5 mg/L cut-off and an age adjusted cut-off. We also evaluated a new and elevated cut-off. Cases were categorized according to their CTPA result into: no embolism, peripheral embolism, lobar embolism and central embolism. Finally we investigated a possible correlation between d-dimer values and location of embolism. RESULTS: We included 1,051 CTPAs, from which 216 (21%) showed pulmonary embolism. There were concomitant d dimer analyses in 822 CTPA examinations. The current 0.5 mg/L cut-off achieved a sensitivity and NPV of 99%. The age-adjusted cut-off achieved a sensitivity and NPV of 98%, and our suggested cut-off of 0.9 mg/L achieved a sensitivity and NPV of 97%. CONCLUSIONS: We conclude that the elevated d-dimer cut-off of 0.9 mg/L achieved a high sensitivity and NPV, while reducing the number of CTPA by 27%. The correlation between d-dimer values and location of embolisms supports the suggestion of an elevated d-dimer value. PMID- 27386488 TI - PDX1 associated therapy in translational medicine. AB - Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely poor prognosis and a low median survival due to lack of the early and reliable detection and effective therapeutic options, despite improvements observed for many other cancers in last decade. Pancreatic and duodenal homeobox 1 (PDX1), which is a homeodomain-containing transcription factor and a key regulator for insulin gene expression, beta cell maturation and proper beta cell function maintenance in the pancreas. Our previous studies revealed that PDX1 promotes tumorigenesis and it is a promising therapeutic target for PDAC. For translational purposes, we developed three therapeutic platforms utilizing RNA interference (RNAi), gene therapy and small inhibitory drug targeting PDX1, and further validated them in PDAC preclinical models both in vitro and in vivo. These PDX1 targeted therapies significantly inhibited PDX1 expression in PDAC cells, ablated PDX1-expressing human PDAC xenograft tumor growth, and prolonged survival in the PDAC mouse models. The data from these preclinical studies proved the translational potentials of PDX1 targeted therapies in PDAC and suggest that the strategy of developing PDX1 targeted therapies would permit a rapid bench-to bedside translation of other relevant gene therapies, which would eventually benefit the patients suffering from this deadly disease. PMID- 27386487 TI - Management and postoperative outcome in primary lung cancer and heart disease co morbidity: a systematic review and meta-analysis. AB - BACKGROUND: Co-morbidity of primary lung cancer (LC) and heart disease (HD), both requiring surgical therapy, characterizes a high risk group of patients necessitating prompt diagnosis and treatment. The aim of this study is the review of available evidence guiding the management of these patients. METHODS: Postoperative outcome of patients operated for primary LC (first meta-analysis) and for both primary LC and HD co-morbidity (second meta-analysis), were studied. Parameters examined in both meta-analyses were thirty-day postoperative mortality, postoperative complications, three- and five-year survival probabilities. The last 36 years were reviewed by using the PubMed data base. Thirty-seven studies were qualified for both meta-analyses. RESULTS: The pooled 30-day mortality percentages (%) were 4.16% [95% confidence interval (CI): 2.68 5.95] (first meta-analysis) and 5.26% (95% CI: 3.47-7.62) (second meta-analysis). Higher percentages of squamous histology and lobectomy, were significantly associated with increased (P=0.001) and decreased (P<0.001) thirty-day postoperative mortality, respectively (first meta-analysis). The pooled percentages for postoperative complications were 34.32% (95% CI: 24.59-44.75) (first meta-analysis) and 45.59% (95% CI: 35.62-55.74) (second meta-analysis). Higher percentages of squamous histology (P=0.001), lobectomy (P=0.002) and p-T1 or p-T2 (P=0.034) were associated with higher proportions of postoperative complications (second meta-analysis). The pooled three- and five- year survival probabilities were 68.25% (95% CI: 45.93-86.86) and 52.03% (95% CI: 34.71-69.11), respectively. Higher mean age (P=0.046) and percentage lobectomy (P=0.009) significantly reduced the five-year survival probability. CONCLUSIONS: Lobectomy and age were both accompanied by reduced five-year survival rate. Also, combined aorto-coronary bypass grafting (CABG) with lobectomy for squamous pT1 or pT2 LC displayed a higher risk of postoperative complications. Moreover, medical decision between combined or staged surgery is suggested to be individualized based on adequacy of coronary arterial perfusion, age, patient's preoperative performance status (taking into account possible co-morbidities per patient), tumor's staging and extent of lung resection. PMID- 27386490 TI - In vitro reactivity ("organ chamber") of guinea pig tracheal rings-methodology considerations. AB - The present text was motivated by the difficulties faced by our postgraduate students when using airways studies protocols and will take into consideration the three mechanisms of relaxation: (I) guanosine 3,5-cyclic monophosphate (cGMP)/NO-dependent; (II) adenosine 3,5-cyclic monophosphate (cAMP)/PGI2 dependent, and (III) hyperpolarization-dependent. Tracheal rings are studied in an organ bath containing a gassed physiological salt solution, usually at a temperature of 37 degrees C. An agent or procedure that causes contraction [acetylcholine (Ach) or metacholine] of the smooth muscle is needed before study airway dilator drugs. The presented airways studies protocols are useful to study the bronchial epithelial-dependent reactivity. PMID- 27386489 TI - The role of pembrolizumab in the treatment of advanced non-small cell lung cancer. AB - Lung cancer is the leading cause of death cancer related worldwide. The standard therapies have unmet medical needs both due to the limited activity and relevant toxicity of platinum-based chemotherapy and to the low frequency of specific alterations required to use targeted therapies. Immune checkpoint inhibition due to restoring the immune system's capacity to eradicate tumors is undergoing in extensive investigation in non-small cell lung cancer (NSCLC) as a new treatment approach. Programmed cell death protein-1 (PD-1) and its ligand, programmed cell death-ligand 1 (PD-L1) have recently led to significantly and durable improvements in the clinical outcome of several kind of tumors including lung cancer. Pembrolizumab, approved by the U.S. FDA for the treatment of advanced NSCLC progressed after other therapies and with expression of PD-L1, has demonstrated durable response and prolonged overall survival (OS) especially in patients with high PD-L1 expression. Further investigation are needed to improve treatment outcomes through combination of immunotherapy or combined with other targeted therapies. PMID- 27386492 TI - Introduction to machine learning: k-nearest neighbors. AB - Machine learning techniques have been widely used in many scientific fields, but its use in medical literature is limited partly because of technical difficulties. k-nearest neighbors (kNN) is a simple method of machine learning. The article introduces some basic ideas underlying the kNN algorithm, and then focuses on how to perform kNN modeling with R. The dataset should be prepared before running the knn() function in R. After prediction of outcome with kNN algorithm, the diagnostic performance of the model should be checked. Average accuracy is the mostly widely used statistic to reflect the kNN algorithm. Factors such as k value, distance calculation and choice of appropriate predictors all have significant impact on the model performance. PMID- 27386491 TI - The implication and potential applications of high-mobility group box 1 protein in breast cancer. AB - High-mobility group box 1 protein (HMGB1) is a highly conserved, non-histone and ubiquitous chromosomal protein found enriched in active chromatin forming part of the high mobility group family of proteins and is encoded by the HMGB1 gene (13q12) in human beings. It has various intranuclear and extracellular functions. It plays an important role in the pathogenesis of many diseases including cancer. In 2012, there was approximately 1.67 million new breast cancer cases diagnosed which makes it the second most frequent cancer in the world after lung cancer (25% of all cancers) and the commonest cancer among women. Both pre-clinical and clinical studies have suggested that HMGB1 might be a useful target in the management of breast cancer. This review summarises the structure and functions of HMGB1 and its dual role in carcinogenesis both as a pro-tumorigenic and anti tumorigenic factor. It also sums up evidence from in vitro and in vivo studies using breast cancer cell lines and samples which demonstrate its influence in radiotherapy, chemotherapy and hormonal therapy in breast cancer. It may have particular importance in HER2 positive and metastatic breast cancer. It might pave the way for new breast cancer treatments through development of novel drugs, use of microRNAs (miRNAs), targeting breast cancer stem cells (CSCs) and breast cancer immunotherapy. It may also play a role in determining breast cancer prognosis. Thus HMGB1 may open up novel avenues in breast cancer management. PMID- 27386493 TI - Anterior cruciate ligament ganglion causing flexion restriction: a case report and review of literature. AB - Ganglion cysts originating from the anterior cruciate ligament (ACL) are uncommon. Often asymptomatic, they infrequently present with non-specific symptoms such as knee pain, stiffness, clicks, locking or restriction of knee extension. However, the patient we report presented with knee flexion restriction. A 37-year-old Chinese gentleman, with no history of knee trauma, presented with left knee pain. Left knee range of motion (ROM) was from 0 to 110 degrees. Magnetic resonance imaging (MRI) scan revealed a 1.5 cm * 3.3 cm * 1.7 cm cyst located in the intercondylar region arising from the ACL and extending predominantly posteriorly. Arthroscopy confirmed an intrasubstance ACL ganglion cyst, which was extending posteriorly. Complete excision of the cyst was performed. At 1-year follow-up, the patient regained knee flexion of 130 degrees. We describe one of the largest ACL ganglion cysts. Such cysts often extend anteriorly and impinge onto the roof of the intercondylar notch during knee extension, thus restricting extension. The restriction in knee motion in our patient was in flexion instead; this was because the cyst took an unusual course of extension predominantly in the posterior direction. Although rare, it must be included as a possible differential diagnosis when patients present with such knee symptoms. PMID- 27386494 TI - Primary extraskeletal pleural osteosarcoma: a rare pleural identity. AB - A 69-year-old female with a history of a heart transplant 16 years prior, presented with a large left chest mass identified on fluoroscopy in the cardiac catheterization lab. The patient noted a 40 pound weight loss in one year. A chest X-ray (CXR) and chest computed tomography (CT) demonstrated a large complex cystic mass in the left chest. A CT guided aspiration was performed, and the cytology for the cyst fluid was negative for malignancy. The patient continued to have worsening shortness of breath, a repeat chest CT scan and magnetic resonance imaging (MRI) three months later, demonstrated a recurrence of the left pleural mass. Further, work-up was negative for tumor. A left video assisted thoracotomy exploration was performed and left thoracotomy was needed for the mass resection. The final pathology demonstrated a high grade osteosarcoma. The post-operative course was unremarkable. PMID- 27386496 TI - Which clinical significance has automatic detection of very low levels of nucleated red blood cells in the peripheral blood? PMID- 27386495 TI - Lifelong protection mediated by stem cell-like CD8(+) T memory subset cells (Tscm) induced by vaccination. PMID- 27386497 TI - "Graves disease" behind glucose fluctuation. PMID- 27386498 TI - Predictors of time to initiation of symptomatic therapy in early Parkinson's disease. AB - OBJECTIVE: To determine clinical and biological variables that predict time to initiation of symptomatic therapy in de novo Parkinson's disease patients. METHODS: Parkinson's Progression Markers Initiative is a longitudinal case control study of de novo, untreated Parkinson's disease participants at enrolment. Participants contribute a wide range of motor and non-motor measures, including biofluids and imaging biomarkers. The machine learning method of random survival forests was used to examine the ability of baseline variables to predict time to initiation of symptomatic therapy since study enrollment (baseline). RESULTS: There were 423 PD participants enrolled in PPMI and 33 initial baseline variables. Cross-validation results showed that the three-predictor subset of disease duration (time from diagnosis to enrollment), the modified Schwab and England activities of daily living scale, and the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score modestly predicted time to initiation of symptomatic therapy (C = 0.70, pseudo-R (2) = 0.13). Prediction using the three variables was similar to using the entire set of 33. None of the biological variables increased accuracy of the prediction. A prognostic index for time to initiation of symptomatic therapy was created using the linear and nonlinear effects of the three top variables based on a post hoc Cox model. INTERPRETATION: Our findings using a novel machine learning method support previously reported clinical variables that predict time to initiation of symptomatic therapy. However, the inclusion of biological variables did not increase prediction accuracy. Our prognostic index constructed, based on the group-level survival curve can provide an indication of the risk of initiation of ST for PD patients based on functions of the three top predictors. PMID- 27386499 TI - IVIg attenuates complement and improves spinal cord injury outcomes in mice. AB - OBJECTIVE: Traumatic spinal cord injury (SCI) elicits immediate neural cell death, axonal damage, and disruption of the blood-spinal cord barrier, allowing circulating immune cells and blood proteins into the spinal parenchyma. The inflammatory response to SCI involves robust complement system activation, which contributes to secondary injury and impairs neurological recovery. This study aimed to determine whether intravenous immunoglobulin (IVIg), an FDA-approved treatment for inflammatory conditions, can scavenge complement activation products and improve recovery from contusive SCI. METHODS: We used functional testing, noninvasive imaging, and detailed postmortem analysis to assess whether IVIg therapy is effective in a mouse model of severe contusive SCI. RESULTS: IVIg therapy at doses of 0.5-2 g/kg improved the functional and histopathological outcomes from SCI, conferring protection against lesion enlargement, demyelination, central canal dilation, and axonal degeneration. The benefits of IVIg were detectable through noninvasive diffusion tensor imaging (DTI), with IVIg treatment counteracting the progressive SCI-induced increase in radial diffusivity (RD) in white matter. Diffusion indices significantly correlated with the functional performance of individual mice and accurately predicted the degree of myelin preservation. Further experiments revealed that IVIg therapy reduced the presence of complement activation products and phagocytically active macrophages at the lesion site, providing insight as to its mechanisms of action. INTERPRETATION: Our findings highlight the potential of using IVIg as an immunomodulatory treatment for SCI, and the value of DTI to assess tissue damage and screen for the efficacy of candidate intervention strategies in preclinical models of SCI, both quantitatively and noninvasively. PMID- 27386500 TI - A microRNA-328 binding site in PAX6 is associated with centrotemporal spikes of rolandic epilepsy. AB - OBJECTIVE: Rolandic epilepsy is a common genetic focal epilepsy of childhood characterized by centrotemporal sharp waves on electroencephalogram. In previous genome-wide analysis, we had reported linkage of centrotemporal sharp waves to chromosome 11p13, and fine mapping with 44 SNPs identified the ELP4-PAX6 locus in two independent US and Canadian case-control samples. Here, we aimed to find a causative variant for centrotemporal sharp waves using a larger sample and higher resolution genotyping array. METHODS: We fine-mapped the ELP4-PAX6 locus in 186 individuals from rolandic epilepsy families and 1000 population controls of European origin using the Illumina HumanCoreExome-12 v1.0 BeadChip. Controls were matched to cases on ethnicity using principal component analysis. We used generalized estimating equations to assess association, followed up with a bioinformatics survey and literature search to evaluate functional significance. RESULTS: Homozygosity at the T allele of SNP rs662702 in the 3' untranslated region of PAX6 conferred increased risk of CTS: Odds ratio = 12.29 (95% CI: 3.20 47.22), P = 2.6 * 10(-4) and is seen in 3.9% of cases but only 0.3% of controls. INTERPRETATION: The minor T allele of SNP rs662702 disrupts regulation by microRNA-328, which is known to result in increased PAX6 expression in vitro. This study provides, for the first time, evidence of a noncoding genomic variant contributing to the etiology of a common human epilepsy via a posttranscriptional regulatory mechanism. PMID- 27386501 TI - Deep sequencing of mitochondrial genomes reveals increased mutation load in Friedreich's ataxia. AB - OBJECTIVE: Friedreich's ataxia (FRDA) is an autosomal recessive trinucleotide repeat expansion disorder caused by epigenetic silencing of the frataxin gene (FXN). Current research suggests that damage and variation of mitochondrial DNA (mtDNA) contribute to the molecular pathogenesis of FRDA. We sought to establish the extent of the mutation burden across the mitochondrial genome in FRDA cells and investigate the molecular mechanisms connecting FXN downregulation and the acquisition of mtDNA damage. METHODS: Damage and mutation load in mtDNA of a panel of FRDA and control fibroblasts were determined using qPCR and next generation MiSeq sequencing, respectively. The capacity of FRDA and control cells to repair oxidative lesions in their mtDNA was measured using a quantitative DNA damage assay. Comprehensive RNA sequencing gene expression analyses were conducted to assess the status of DNA repair and metabolism genes in FRDA cells. RESULTS: Acute or prolonged downregulation of FXN expression resulted in a significant increase in mtDNA damage that translated to a significant elevation of mutation load in mtDNA. The predominant mutations identified throughout the mtDNA were C>T, G>A transitions (P = 0.007). Low FXN expression reduced capacity to repair oxidative damage in mtDNA. Downregulation of FXN expression strongly correlated (r = 0.73) with decreased levels of base excision repair (BER) DNA glycosylase NTHL1. INTERPRETATION: Downregulation of FXN expression in FRDA cells elevates mtDNA damage, increases mutation load of the mitochondrial genome, and diminishes DNA repair capacity. Progressive accumulation of mtDNA mutations in vulnerable FRDA patient cells reduces mitochondrial fitness ultimately leading to cell death. PMID- 27386502 TI - Impaired muscle uptake of creatine in spinal and bulbar muscular atrophy. AB - OBJECTIVE: The aim of this study was to explore the pathomechanism underlying the reduction of serum creatinine (Cr) concentrations in spinal and bulbar muscular atrophy (SBMA). METHODS: We evaluated blood chemistries, motor function, and muscle mass measured by dual-energy X-ray absorptiometry in male subjects with SBMA (n = 65), amyotrophic lateral sclerosis (ALS; n = 27), and healthy controls (n = 25). We also examined the intramuscular concentrations of creatine, a precursor of Cr, as well as the protein and mRNA expression levels of the creatine transporter (SLC6A8) in autopsy specimens derived from subjects who had SBMA and ALS and disease controls. Furthermore, we measured the mRNA expression levels of SLC6A8 in cultured muscle cells (C2C12) transfected with the polyglutamine-expanded androgen receptor (AR-97Q). RESULTS: Serum Cr concentrations were significantly lower in subjects with SBMA than in those with ALS (P < 0.001), despite similar muscle mass values. Intramuscular creatine concentrations were also lower in with the autopsied specimen of SBMA subjects than in those with ALS subjects (P = 0.018). Moreover, the protein and mRNA expression levels of muscle SLC6A8 were suppressed in subjects with SBMA. The mRNA levels of SLC6A8 were also suppressed in C2C12 cells bearing AR-97Q. INTERPRETATION: These results suggest that low serum Cr concentration in subjects with SBMA is caused by impaired muscle uptake of creatine in addition to being caused by neurogenic atrophy. Given that creatine serves as an energy source in skeletal muscle, increasing muscle creatine uptake is a possible therapeutic approach for treating SBMA. PMID- 27386503 TI - Neonatal Fc receptor promoter gene polymorphism does not predict pharmacokinetics of IVIg or the clinical course of GBS. AB - Treatment of Guillain-Barre syndrome with a standard course of high-dose intravenous immunoglobulin (IVIg) results in a variable clinical recovery which is associated with changes in serum IgG levels after treatment. The neonatal Fc receptor protects IgG from degradation, and a genetic polymorphism in its promoter region that influences the expression of Fc-receptor, may in part explain the variation in IgG levels and outcome. This polymorphism was determined by polymerase chain reaction in a cohort of 257 patients with Guillain-Barre syndrome treated with IVIg. We could not demonstrate a relation between this polymorphism, the pharmacokinetics of IVIg, or the clinical course and outcome. PMID- 27386504 TI - Rituximab in refractory myasthenia gravis: a prospective, open-label study with long-term follow-up. AB - We examined the clinical effectiveness of rituximab in fourteen patients with refractory myasthenia gravis (MG). Manual muscle testing (MMT) score was recorded at baseline and followed during the course of the study. Steroid dose, frequency of intravenous immunoglobulin (IVIG) infusions, and plasma exchange (PLEX) were also monitored throughout the duration of the study. All patients responded dramatically to rituximab, as measured by a change in MMT score, prednisone dose, or the frequency of IVIG infusions or PLEX. Rituximab appears safe and effective for the treatment of refractory MG. It should be considered as a therapeutic option in refractory patients. PMID- 27386505 TI - Arterial ischemic stroke in HIV: Defining and classifying etiology for research studies. AB - HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke. PMID- 27386506 TI - Absence of systemic oxidative stress and increased CSF prostaglandin F2alpha in progressive MS. AB - OBJECTIVE: We aimed to investigate the role of oxidative stress in the progression of multiple sclerosis (MS). METHODS: We determined by liquid chromatography-tandem mass spectrometry nonenzymatic (F2-isoprostanes) and enzymatic oxidation products of arachidonic acid (prostaglandin F2alpha [PGF2alpha]) in plasma and CSF of 45 controls (other neurologic disease [OND] with no signs of inflammation) and 62 patients with MS. Oxidation products were correlated with disease severity and validated biomarkers of inflammation (chemokine ligand 13; matrix metalloproteinase-9; osteopontin) and axonal damage (neurofilament light protein). RESULTS: Compared with OND controls, plasma concentrations of F2-isoprostanes and PGF2alpha were significantly lower in patients with progressive disease, and decreased with increasing disability score (Expanded Disability Status Scale). In contrast, CSF concentrations of PGF2alpha, but not F2-isoprostanes, were significantly higher in patients with progressive disease than OND controls (p < 0.01). The content of PGF2alpha in CSF increased with disease severity (p = 0.044) and patient age (p = 0.022), although this increase could not be explained by age. CSF PGF2alpha decreased with natalizumab and methylprednisolone treatment and was unaffected by the use of nonsteroidal anti-inflammatory drug in secondary progressive MS. CSF PGF2alpha did not associate with validated CSF markers of inflammation and axonal damage that themselves did not associate with the Expanded Disability Status Scale. CONCLUSIONS: Our data suggest that MS progression is associated with low systemic oxidative activity. This may contribute to immune dysregulation with CNS inflammation accompanied by increased local cyclooxygenase-dependent lipid oxidation. PMID- 27386507 TI - Macroecological drivers of archaea and bacteria in benthic deep-sea ecosystems. AB - Bacteria and archaea dominate the biomass of benthic deep-sea ecosystems at all latitudes, playing a crucial role in global biogeochemical cycles, but their macroscale patterns and macroecological drivers are still largely unknown. We show the results of the most extensive field study conducted so far to investigate patterns and drivers of the distribution and structure of benthic prokaryote assemblages from 228 samples collected at latitudes comprising 34 degrees N to 79 degrees N, and from ca. 400- to 5570-m depth. We provide evidence that, in deep-sea ecosystems, benthic bacterial and archaeal abundances significantly increase from middle to high latitudes, with patterns more pronounced for archaea, and particularly for Marine Group I Thaumarchaeota. Our results also reveal that different microbial components show varying sensitivities to changes in temperature conditions and food supply. We conclude that climate change will primarily affect deep-sea benthic archaea, with important consequences on global biogeochemical cycles, particularly at high latitudes. PMID- 27386508 TI - Pre-Gondwanan-breakup origin of Beauprea (Proteaceae) explains its historical presence in New Caledonia and New Zealand. AB - New Caledonia and New Zealand belong to the now largely submerged continent Zealandia. Their high levels of endemism and species richness are usually considered the result of transoceanic dispersal events followed by diversification after they re-emerged from the Pacific Ocean in the mid-Cenozoic. We explore the origin and evolutionary history of Beauprea (Proteaceae), which is now endemic to New Caledonia but was once spread throughout eastern Gondwana, including New Zealand. We review the extensive Beauprea-type pollen data in the fossil records and analyze the relationship of these fossil taxa to extant genera within Proteaceae. We further reconstruct the phylogenetic relations among nine extant species of Beauprea and estimate the age of the Beauprea clade. By incorporating extinct taxa into the Beauprea phylogenetic tree, we reconstruct the ancient distribution of this genus. Our analysis shows that Beauprea originated c. 88 Ma (million years ago) in Antarctica-Southeastern Australia and spread throughout Gondwana before its complete breakup. We propose that Beauprea, already existing as two lineages, was carried with Zealandia when it separated from the rest of Gondwana c. 82 Ma, thus supporting an autochthonous origin for Beauprea species now in New Caledonia and historically in New Zealand up to 1 Ma. We show that the presence of Beauprea through transoceanic dispersal is implausible. This means that neither New Caledonia nor New Zealand has been entirely submerged since the Upper Cretaceous; thus, possible vicariance and allopatry must be taken into account when considering the high levels of endemism and species richness of these island groups. PMID- 27386509 TI - Surface-atmosphere decoupling limits accumulation at Summit, Greenland. AB - Despite rapid melting in the coastal regions of the Greenland Ice Sheet, a significant area (~40%) of the ice sheet rarely experiences surface melting. In these regions, the controls on annual accumulation are poorly constrained owing to surface conditions (for example, surface clouds, blowing snow, and surface inversions), which render moisture flux estimates from myriad approaches (that is, eddy covariance, remote sensing, and direct observations) highly uncertain. Accumulation is partially determined by the temperature dependence of saturation vapor pressure, which influences the maximum humidity of air parcels reaching the ice sheet interior. However, independent proxies for surface temperature and accumulation from ice cores show that the response of accumulation to temperature is variable and not generally consistent with a purely thermodynamic control. Using three years of stable water vapor isotope profiles from a high altitude site on the Greenland Ice Sheet, we show that as the boundary layer becomes increasingly stable, a decoupling between the ice sheet and atmosphere occurs. The limited interaction between the ice sheet surface and free tropospheric air reduces the capacity for surface condensation to achieve the rate set by the humidity of the air parcels reaching interior Greenland. The isolation of the surface also acts to recycle sublimated moisture by recondensing it onto fog particles, which returns the moisture back to the surface through gravitational settling. The observations highlight a unique mechanism by which ice sheet mass is conserved, which has implications for understanding both past and future changes in accumulation rate and the isotopic signal in ice cores from Greenland. PMID- 27386510 TI - Saturation of recognition elements blocks evolution of new tRNA identities. AB - Understanding the principles that led to the current complexity of the genetic code is a central question in evolution. Expansion of the genetic code required the selection of new transfer RNAs (tRNAs) with specific recognition signals that allowed them to be matured, modified, aminoacylated, and processed by the ribosome without compromising the fidelity or efficiency of protein synthesis. We show that saturation of recognition signals blocks the emergence of new tRNA identities and that the rate of nucleotide substitutions in tRNAs is higher in species with fewer tRNA genes. We propose that the growth of the genetic code stalled because a limit was reached in the number of identity elements that can be effectively used in the tRNA structure. PMID- 27386511 TI - Optical pi phase shift created with a single-photon pulse. AB - A deterministic photon-photon quantum logic gate is a long-standing goal. Building such a gate becomes possible if a light pulse containing only one photon imprints a phase shift of pi onto another light field. We experimentally demonstrate the generation of such a pi phase shift with a single-photon pulse. A first light pulse containing less than one photon on average is stored in an atomic gas. Rydberg blockade combined with electromagnetically induced transparency creates a phase shift for a second light pulse, which propagates through the medium. We measure the pi phase shift of the second pulse when we postselect the data upon the detection of a retrieved photon from the first pulse. This demonstrates a crucial step toward a photon-photon gate and offers a variety of applications in the field of quantum information processing. PMID- 27386512 TI - Inner solar system material discovered in the Oort cloud. AB - We have observed C/2014 S3 (PANSTARRS), a recently discovered object on a cometary orbit coming from the Oort cloud that is physically similar to an inner main belt rocky S-type asteroid. Recent dynamical models successfully reproduce the key characteristics of our current solar system; some of these models require significant migration of the giant planets, whereas others do not. These models provide different predictions on the presence of rocky material expelled from the inner solar system in the Oort cloud. C/2014 S3 could be the key to verifying these predictions of the migration-based dynamical models. Furthermore, this object displays a very faint, weak level of comet-like activity, five to six orders of magnitude less than that of typical ice-rich comets on similar Orbits coming from the Oort cloud. For the nearly tailless appearance, we are calling C/2014 S3 a Manx object. Various arguments convince us that this activity is produced by sublimation of volatile ice, that is, normal cometary activity. The activity implies that C/2014 S3 has retained a tiny fraction of the water that is expected to be present at its formation distance in the inner solar system. We may be looking at fresh inner solar system Earth-forming material that was ejected from the inner solar system and preserved for billions of years in the Oort cloud. PMID- 27386514 TI - Retraction of the Research Article: "Individualistic sensitivities and exposure to climate change explain variation in species' distribution and abundance changes". AB - [This retracts the article on p. e1400220 in vol. 1, PMID: 26601276.]. PMID- 27386513 TI - Reduced evolutionary rate in reemerged Ebola virus transmission chains. AB - On 29 June 2015, Liberia's respite from Ebola virus disease (EVD) was interrupted for the second time by a renewed outbreak ("flare-up") of seven confirmed cases. We demonstrate that, similar to the March 2015 flare-up associated with sexual transmission, this new flare-up was a reemergence of a Liberian transmission chain originating from a persistently infected source rather than a reintroduction from a reservoir or a neighboring country with active transmission. Although distinct, Ebola virus (EBOV) genomes from both flare-ups exhibit significantly low genetic divergence, indicating a reduced rate of EBOV evolution during persistent infection. Using this rate of change as a signature, we identified two additional EVD clusters that possibly arose from persistently infected sources. These findings highlight the risk of EVD flare-ups even after an outbreak is declared over. PMID- 27386515 TI - Genetic markers for antioxidant capacity in a reef-building coral. AB - The current lack of understanding of the genetic basis underlying environmental stress tolerance in reef-building corals impairs the development of new management approaches to confronting the global demise of coral reefs. On the Great Barrier Reef (GBR), an approximately 51% decline in coral cover occurred over the period 1985-2012. We conducted a gene-by-environment association analysis across 12 degrees latitude on the GBR, as well as both in situ and laboratory genotype-by-phenotype association analyses. These analyses allowed us to identify alleles at two genetic loci that account for differences in environmental stress tolerance and antioxidant capacity in the common coral Acropora millepora. The effect size for antioxidant capacity was considerable and biologically relevant (32.5 and 14.6% for the two loci). Antioxidant capacity is a critical component of stress tolerance because a multitude of environmental stressors cause increased cellular levels of reactive oxygen species. Our findings provide the first step toward the development of novel coral reef management approaches, such as spatial mapping of stress tolerance for use in marine protected area design, identification of stress-tolerant colonies for assisted migration, and marker-assisted selective breeding to create more tolerant genotypes for restoration of denuded reefs. PMID- 27386516 TI - Mutation at a distance caused by homopolymeric guanine repeats in Saccharomyces cerevisiae. AB - Mutation provides the raw material from which natural selection shapes adaptations. The rate at which new mutations arise is therefore a key factor that determines the tempo and mode of evolution. However, an accurate assessment of the mutation rate of a given organism is difficult because mutation rate varies on a fine scale within a genome. A central challenge of evolutionary genetics is to determine the underlying causes of this variation. In earlier work, we had shown that repeat sequences not only are prone to a high rate of expansion and contraction but also can cause an increase in mutation rate (on the order of kilobases) of the sequence surrounding the repeat. We perform experiments that show that simple guanine repeats 13 bp (base pairs) in length or longer (G 13+ ) increase the substitution rate 4- to 18-fold in the downstream DNA sequence, and this correlates with DNA replication timing (R = 0.89). We show that G 13+ mutagenicity results from the interplay of both error-prone translesion synthesis and homologous recombination repair pathways. The mutagenic repeats that we study have the potential to be exploited for the artificial elevation of mutation rate in systems biology and synthetic biology applications. PMID- 27386517 TI - Structural basis of Dscam1 homodimerization: Insights into context constraint for protein recognition. AB - The Drosophila neural receptor Dscam1 (Down syndrome cell adhesion molecule 1) plays an essential role in neuronal wiring and self-avoidance. Dscam1 potentially encodes 19,008 ectodomains through alternative RNA splicing and exhibits exquisite isoform-specific homophilic binding, which makes it an exceptional example for studying protein binding specificity. However, structural information on Dscam1 is limited, which hinders illumination of the mechanism of Dscam1 isoform-specific recognition. Whether different Dscam1 isoforms adopt the same dimerization mode remains a subject of debate. We present 12 Dscam1 crystal structures, provide direct evidence indicating that all isoforms adopt a conserved homodimer geometry in a modular fashion, identify two mechanisms for the Ig2 binding domain to dispel electrostatic repulsion during dimerization, decode Ig2 binding specificity by a central motif at its symmetry center, uncover the role of glycosylation in Dscam1 homodimerization, and find electrostatic potential complementarity to help define the binding region and the antiparallel binding mode. We then propose a concept that the context of a protein may set restrictions to regulate its binding specificity, which provides a better understanding of protein recognition. PMID- 27386518 TI - Broadband and chiral binary dielectric meta-holograms. AB - Subwavelength structured surfaces, known as meta-surfaces, hold promise for future compact and optically thin devices with versatile functionalities. By revisiting the concept of detour phase, we demonstrate high-efficiency holograms with broadband and chiral imaging functionalities. In our devices, the apertures of binary holograms are replaced by subwavelength structured microgratings. We achieve broadband operation from the visible to the near infrared and efficiency as high as 75% in the 1.0 to 1.4 MUm range by compensating for the inherent dispersion of the detour phase with that of the subwavelength structure. In addition, we demonstrate chiral holograms that project different images depending on the handedness of the reference beam by incorporating a geometric phase. Our devices' compactness, lightness, and ability to produce images even at large angles have significant potential for important emerging applications such as wearable optics. PMID- 27386519 TI - Pan-ice-sheet glacier terminus change in East Antarctica reveals sensitivity of Wilkes Land to sea-ice changes. AB - The dynamics of ocean-terminating outlet glaciers are an important component of ice-sheet mass balance. Using satellite imagery for the past 40 years, we compile an approximately decadal record of outlet-glacier terminus position change around the entire East Antarctic Ice Sheet (EAIS) marine margin. We find that most outlet glaciers retreated during the period 1974-1990, before switching to advance in every drainage basin during the two most recent periods, 1990-2000 and 2000-2012. The only exception to this trend was in Wilkes Land, where the majority of glaciers (74%) retreated between 2000 and 2012. We hypothesize that this anomalous retreat is linked to a reduction in sea ice and associated impacts on ocean stratification, which increases the incursion of warm deep water toward glacier termini. Because Wilkes Land overlies a large marine basin, it raises the possibility of a future sea level contribution from this sector of East Antarctica. PMID- 27386521 TI - Far-field super-resolution imaging of resonant multiples. AB - We demonstrate for the first time that seismic resonant multiples, usually considered as noise, can be used for super-resolution imaging in the far-field region of sources and receivers. Tests with both synthetic data and field data show that resonant multiples can image reflector boundaries with resolutions more than twice the classical resolution limit. Resolution increases with the order of the resonant multiples. This procedure has important applications in earthquake and exploration seismology, radar, sonar, LIDAR (light detection and ranging), and ultrasound imaging, where the multiples can be used to make high-resolution images. PMID- 27386520 TI - Octopamine connects nutrient cues to lipid metabolism upon nutrient deprivation. AB - Starvation is probably the most common stressful situation in nature. In vertebrates, elevation of the biogenic amine norepinephrine levels is common during starvation. However, the precise role of norepinephrine in nutrient deprivation remains largely unknown. We report that in the free-living nematode Caenorhabditis elegans, up-regulation of the biosynthesis of octopamine, the invertebrate counterpart of norepinephrine, serves as a mechanism to adapt to starvation. During nutrient deprivation, the nuclear receptor DAF-12, known to sense nutritional cues, up-regulates the expression of tbh-1 that encodes tyramine beta-hydroxylase, a key enzyme for octopamine biosynthesis, in the RIC neurons. Octopamine induces the expression of the lipase gene lips-6 via its receptor SER-3 in the intestine. LIPS-6, in turn, elicits lipid mobilization. Our findings reveal that octopamine acts as an endocrine regulator linking nutrient cues to lipolysis to maintain energy homeostasis, and suggest that such a mechanism may be evolutionally conserved in diverse organisms. PMID- 27386523 TI - Topological nature of nonlinear optical effects in solids. AB - There are a variety of nonlinear optical effects including higher harmonic generations, photovoltaic effects, and nonlinear Kerr rotations. They are realized by strong light irradiation to materials that results in nonlinear polarizations in the electric field. These are of great importance in studying the physics of excited states of the system as well as for applications to optical devices and solar cells. Nonlinear properties of materials are usually described by nonlinear susceptibilities, which have complex expressions including many matrix elements and energy denominators. On the other hand, a nonequilibrium steady state under an electric field periodic in time has a concise description in terms of the Floquet bands of electrons dressed by photons. We show theoretically, using the Floquet formalism, that various nonlinear optical effects, such as the shift current in noncentrosymmetric materials, photovoltaic Hall response, and photo-induced change of order parameters under the continuous irradiation of monochromatic light, can be described in a unified fashion by topological quantities involving the Berry connection and Berry curvature. We found that vector fields defined with the Berry connections in the space of momentum and/or parameters govern the nonlinear responses. This topological view offers a route to designing nonlinear optical materials. PMID- 27386522 TI - Ricci curvature: An economic indicator for market fragility and systemic risk. AB - Quantifying the systemic risk and fragility of financial systems is of vital importance in analyzing market efficiency, deciding on portfolio allocation, and containing financial contagions. At a high level, financial systems may be represented as weighted graphs that characterize the complex web of interacting agents and information flow (for example, debt, stock returns, and shareholder ownership). Such a representation often turns out to provide keen insights. We show that fragility is a system-level characteristic of "business-as-usual" market behavior and that financial crashes are invariably preceded by system level changes in robustness. This was done by leveraging previous work, which suggests that Ricci curvature, a key geometric feature of a given network, is negatively correlated to increases in network fragility. To illustrate this insight, we examine daily returns from a set of stocks comprising the Standard and Poor's 500 (S&P 500) over a 15-year span to highlight the fact that corresponding changes in Ricci curvature constitute a financial "crash hallmark." This work lays the foundation of understanding how to design (banking) systems and policy regulations in a manner that can combat financial instabilities exposed during the 2007-2008 crisis. PMID- 27386524 TI - Monitoring southwest Greenland's ice sheet melt with ambient seismic noise. AB - The Greenland ice sheet presently accounts for ~70% of global ice sheet mass loss. Because this mass loss is associated with sea-level rise at a rate of 0.7 mm/year, the development of improved monitoring techniques to observe ongoing changes in ice sheet mass balance is of paramount concern. Spaceborne mass balance techniques are commonly used; however, they are inadequate for many purposes because of their low spatial and/or temporal resolution. We demonstrate that small variations in seismic wave speed in Earth's crust, as measured with the correlation of seismic noise, may be used to infer seasonal ice sheet mass balance. Seasonal loading and unloading of glacial mass induces strain in the crust, and these strains then result in seismic velocity changes due to poroelastic processes. Our method provides a new and independent way of monitoring (in near real time) ice sheet mass balance, yielding new constraints on ice sheet evolution and its contribution to global sea-level changes. An increased number of seismic stations in the vicinity of ice sheets will enhance our ability to create detailed space-time records of ice mass variations. PMID- 27386525 TI - North Atlantic salinity as a predictor of Sahel rainfall. AB - Water evaporating from the ocean sustains precipitation on land. This ocean-to land moisture transport leaves an imprint on sea surface salinity (SSS). Thus, the question arises of whether variations in SSS can provide insight into terrestrial precipitation. This study provides evidence that springtime SSS in the subtropical North Atlantic ocean can be used as a predictor of terrestrial precipitation during the subsequent summer monsoon in Africa. Specifically, increased springtime SSS in the central to eastern subtropical North Atlantic tends to be followed by above-normal monsoon-season precipitation in the African Sahel. In the spring, high SSS is associated with enhanced moisture flux divergence from the subtropical oceans, which converges over the African Sahel and helps to elevate local soil moisture content. From spring to the summer monsoon season, the initial water cycling signal is preserved, amplified, and manifested in excessive precipitation. According to our analysis of currently available soil moisture data sets, this 3-month delay is attributable to a positive coupling between soil moisture, moisture flux convergence, and precipitation in the Sahel. Because of the physical connection between salinity, ocean-to-land moisture transport, and local soil moisture feedback, seasonal forecasts of Sahel precipitation can be improved by incorporating SSS into prediction models. Thus, expanded monitoring of ocean salinity should contribute to more skillful predictions of precipitation in vulnerable subtropical regions, such as the Sahel. PMID- 27386526 TI - Dehydration of chlorite explains anomalously high electrical conductivity in the mantle wedges. AB - Mantle wedge regions in subduction zone settings show anomalously high electrical conductivity (~1 S/m) that has often been attributed to the presence of aqueous fluids released by slab dehydration. Laboratory-based measurements of the electrical conductivity of hydrous phases and aqueous fluids are significantly lower and cannot readily explain the geophysically observed anomalously high electrical conductivity. The released aqueous fluid also rehydrates the mantle wedge and stabilizes a suite of hydrous phases, including serpentine and chlorite. In this present study, we have measured the electrical conductivity of a natural chlorite at pressures and temperatures relevant for the subduction zone setting. In our experiment, we observe two distinct conductivity enhancements when chlorite is heated to temperatures beyond its thermodynamic stability field. The initial increase in electrical conductivity to ~3 * 10(-3) S/m can be attributed to chlorite dehydration and the release of aqueous fluids. This is followed by a unique, subsequent enhancement of electrical conductivity of up to 7 * 10(-1) S/m. This is related to the growth of an interconnected network of a highly conductive and chemically impure magnetite mineral phase. Thus, the dehydration of chlorite and associated processes are likely to be crucial in explaining the anomalously high electrical conductivity observed in mantle wedges. Chlorite dehydration in the mantle wedge provides an additional source of aqueous fluid above the slab and could also be responsible for the fixed depth (120 +/- 40 km) of melting at the top of the subducting slab beneath the subduction-related volcanic arc front. PMID- 27386527 TI - Exopolysaccharide biosynthetic glycoside hydrolases can be utilized to disrupt and prevent Pseudomonas aeruginosa biofilms. AB - Bacterial biofilms present a significant medical challenge because they are recalcitrant to current therapeutic regimes. A key component of biofilm formation in the opportunistic human pathogen Pseudomonas aeruginosa is the biosynthesis of the exopolysaccharides Pel and Psl, which are involved in the formation and maintenance of the structural biofilm scaffold and protection against antimicrobials and host defenses. Given that the glycoside hydrolases PelAh and PslGh encoded in the pel and psl biosynthetic operons, respectively, are utilized for in vivo exopolysaccharide processing, we reasoned that these would provide specificity to target P. aeruginosa biofilms. Evaluating these enzymes as potential therapeutics, we demonstrate that these glycoside hydrolases selectively target and degrade the exopolysaccharide component of the biofilm matrix. PelAh and PslGh inhibit biofilm formation over a 24-hour period with a half maximal effective concentration (EC50) of 69.3 +/- 1.2 and 4.1 +/- 1.1 nM, respectively, and are capable of disrupting preexisting biofilms in 1 hour with EC50 of 35.7 +/- 1.1 and 12.9 +/- 1.1 nM, respectively. This treatment was effective against clinical and environmental P. aeruginosa isolates and reduced biofilm biomass by 58 to 94%. These noncytotoxic enzymes potentiated antibiotics because the addition of either enzyme to a sublethal concentration of colistin reduced viable bacterial counts by 2.5 orders of magnitude when used either prophylactically or on established 24-hour biofilms. In addition, PelAh was able to increase neutrophil killing by ~50%. This work illustrates the feasibility and benefits of using bacterial exopolysaccharide biosynthetic glycoside hydrolases to develop novel antibiofilm therapeutics. PMID- 27386529 TI - The earliest herbivorous marine reptile and its remarkable jaw apparatus. AB - Newly discovered fossils of the Middle Triassic reptile Atopodentatus unicus call for a radical reassessment of its feeding behavior. The skull displays a pronounced hammerhead shape that was hitherto unknown. The long, straight anterior edges of both upper and lower jaws were lined with batteries of chisel shaped teeth, whereas the remaining parts of the jaw rami supported densely packed needle-shaped teeth forming a mesh. The evidence indicates a novel feeding mechanism wherein the chisel-shaped teeth were used to scrape algae off the substrate, and the plant matter that was loosened was filtered from the water column through the more posteriorly positioned tooth mesh. This is the oldest record of herbivory within marine reptiles. PMID- 27386530 TI - On-demand transfer of trapped photons on a chip. AB - Photonic crystal nanocavities, which have modal volumes of the order of a cubic wavelength in the material, are of great interest as flexible platforms for manipulating photons. Recent developments in ultra-high quality factor nanocavities with long photon lifetimes have encouraged us to develop an ultra compact and flexible photon manipulation technology where photons are trapped in networks of such nanocavities. The most fundamental requirement is the on-demand transfer of photons to and from the trapped states of arbitrary nanocavities. We experimentally demonstrate photon transfer between two nearly resonant nanocavities at arbitrary positions on a chip, triggered by the irradiation of a third nonresonant nanocavity using an optical control pulse. We obtain a high transfer efficiency of ~90% with a photon lifetime of ~200 ps. PMID- 27386531 TI - A global quantification of "normal" sleep schedules using smartphone data. AB - The influence of the circadian clock on sleep scheduling has been studied extensively in the laboratory; however, the effects of society on sleep remain largely unquantified. We show how a smartphone app that we have developed, ENTRAIN, accurately collects data on sleep habits around the world. Through mathematical modeling and statistics, we find that social pressures weaken and/or conceal biological drives in the evening, leading individuals to delay their bedtime and shorten their sleep. A country's average bedtime, but not average wake time, predicts sleep duration. We further show that mathematical models based on controlled laboratory experiments predict qualitative trends in sunrise, sunset, and light level; however, these effects are attenuated in the real world around bedtime. Additionally, we find that women schedule more sleep than men and that users reporting that they are typically exposed to outdoor light go to sleep earlier and sleep more than those reporting indoor light. Finally, we find that age is the primary determinant of sleep timing, and that age plays an important role in the variability of population-level sleep habits. This work better defines and personalizes "normal" sleep, produces hypotheses for future testing in the laboratory, and suggests important ways to counteract the global sleep crisis. PMID- 27386528 TI - Carbon sequestration potential of second-growth forest regeneration in the Latin American tropics. AB - Regrowth of tropical secondary forests following complete or nearly complete removal of forest vegetation actively stores carbon in aboveground biomass, partially counterbalancing carbon emissions from deforestation, forest degradation, burning of fossil fuels, and other anthropogenic sources. We estimate the age and spatial extent of lowland second-growth forests in the Latin American tropics and model their potential aboveground carbon accumulation over four decades. Our model shows that, in 2008, second-growth forests (1 to 60 years old) covered 2.4 million km(2) of land (28.1% of the total study area). Over 40 years, these lands can potentially accumulate a total aboveground carbon stock of 8.48 Pg C (petagrams of carbon) in aboveground biomass via low-cost natural regeneration or assisted regeneration, corresponding to a total CO2 sequestration of 31.09 Pg CO2. This total is equivalent to carbon emissions from fossil fuel use and industrial processes in all of Latin America and the Caribbean from 1993 to 2014. Ten countries account for 95% of this carbon storage potential, led by Brazil, Colombia, Mexico, and Venezuela. We model future land-use scenarios to guide national carbon mitigation policies. Permitting natural regeneration on 40% of lowland pastures potentially stores an additional 2.0 Pg C over 40 years. Our study provides information and maps to guide national-level forest-based carbon mitigation plans on the basis of estimated rates of natural regeneration and pasture abandonment. Coupled with avoided deforestation and sustainable forest management, natural regeneration of second-growth forests provides a low-cost mechanism that yields a high carbon sequestration potential with multiple benefits for biodiversity and ecosystem services. PMID- 27386532 TI - Chemical vapor deposition synthesis of near-zigzag single-walled carbon nanotubes with stable tube-catalyst interface. AB - Chemical vapor deposition (CVD) growth is regarded as the most promising method for realizing structure-specific single-walled carbon nanotube (SWNT) growth. In the past 20 years, many efforts dedicated to chirality-selective SWNT growth using various strategies have been reported. However, normal CVD growth under constant conditions could not fully optimize the chirality because the randomly formed cap structure allows the nucleation of all types of SWNTs and the chirality of an SWNT is unlikely to be changed during the following elongation process. We report a new CVD process that allows temperature to be periodically changed to vary SWNT chirality multiple times during elongation to build up the energetically preferred SWNT-catalyst interface. With this strategy, SWNTs with small helix angles (less than 10 degrees ), which are predicted to have lower interfacial formation energy than others, are enriched up to ~72%. Kinetic analysis of the process suggests a multiple redistribution feature whereby a large chiral angle SWNT tends to reach the near-zigzag chirality step by step with a small chiral angle change at each step, and hence, we named this method "tandem plate CVD." This method opens a door to synthesizing chirality-selective SWNTs by rational catalyst design. PMID- 27386533 TI - Measurement of a vacuum-induced geometric phase. AB - Berry's geometric phase naturally appears when a quantum system is driven by an external field whose parameters are slowly and cyclically changed. A variation in the coupling between the system and the external field can also give rise to a geometric phase, even when the field is in the vacuum state or any other Fock state. We demonstrate the appearance of a vacuum-induced Berry phase in an artificial atom, a superconducting transmon, interacting with a single mode of a microwave cavity. As we vary the phase of the interaction, the artificial atom acquires a geometric phase determined by the path traced out in the combined Hilbert space of the atom and the quantum field. Our ability to control this phase opens new possibilities for the geometric manipulation of atom-cavity systems also in the context of quantum information processing. PMID- 27386534 TI - Experimental river delta size set by multiple floods and backwater hydrodynamics. AB - River deltas worldwide are currently under threat of drowning and destruction by sea-level rise, subsidence, and oceanic storms, highlighting the need to quantify their growth processes. Deltas are built through construction of sediment lobes, and emerging theories suggest that the size of delta lobes scales with backwater hydrodynamics, but these ideas are difficult to test on natural deltas that evolve slowly. We show results of the first laboratory delta built through successive deposition of lobes that maintain a constant size. We show that the characteristic size of delta lobes emerges because of a preferential avulsion node-the location where the river course periodically and abruptly shifts-that remains fixed spatially relative to the prograding shoreline. The preferential avulsion node in our experiments is a consequence of multiple river floods and Froude-subcritical flows that produce persistent nonuniform flows and a peak in net channel deposition within the backwater zone of the coastal river. In contrast, experimental deltas without multiple floods produce flows with uniform velocities and delta lobes that lack a characteristic size. Results have broad applications to sustainable management of deltas and for decoding their stratigraphic record on Earth and Mars. PMID- 27386535 TI - Ecosystem context and historical contingency in apex predator recoveries. AB - Habitat loss, overexploitation, and numerous other stressors have caused global declines in apex predators. This "trophic downgrading" has generated widespread concern because of the fundamental role that apex predators can play in ecosystem functioning, disease regulation, and biodiversity maintenance. In attempts to combat declines, managers have conducted reintroductions, imposed stricter harvest regulations, and implemented protected areas. We suggest that full recovery of viable apex predator populations is currently the exception rather than the rule. We argue that, in addition to well-known considerations, such as continued exploitation and slow life histories, there are several underappreciated factors that complicate predator recoveries. These factors include three challenges. First, a priori identification of the suite of trophic interactions, such as resource limitation and competition that will influence recovery can be difficult. Second, defining and accomplishing predator recovery in the context of a dynamic ecosystem requires an appreciation of the timing of recovery, which can determine the relative density of apex predators and other predators and therefore affect competitive outcomes. Third, successful recovery programs require designing adaptive sequences of management strategies that embrace key environmental and species interactions as they emerge. Consideration of recent research on food web modules, alternative stable states, and community assembly offer important insights for predator recovery efforts and restoration ecology more generally. Foremost among these is the importance of a social ecological perspective in facilitating a long-lasting predator restoration while avoiding unintended consequences. PMID- 27386537 TI - Laser vaporization of cirrus-like ice particles with secondary ice multiplication. AB - We investigate the interaction of ultrashort laser filaments with individual 90 MUm ice particles, representative of cirrus particles. The ice particles fragment under laser illumination. By monitoring the evolution of the corresponding ice/vapor system at up to 140,000 frames per second over 30 ms, we conclude that a shockwave vaporization supersaturates the neighboring region relative to ice, allowing the nucleation and growth of new ice particles, supported by laser induced plasma photochemistry. This process constitutes the first direct observation of filament-induced secondary ice multiplication, a process that strongly modifies the particle size distribution and, thus, the albedo of typical cirrus clouds. PMID- 27386536 TI - Synchronization of optical photons for quantum information processing. AB - A fundamental element of quantum information processing with photonic qubits is the nonclassical quantum interference between two photons when they bunch together via the Hong-Ou-Mandel (HOM) effect. Ultimately, many such photons must be processed in complex interferometric networks. For this purpose, it is essential to synchronize the arrival times of the flying photons and to keep their purities high. On the basis of the recent experimental success of single photon storage with high purity, we demonstrate for the first time the HOM interference of two heralded, nearly pure optical photons synchronized through two independent quantum memories. Controlled storage times of up to 1.8 MUs for about 90 events per second were achieved with purities that were sufficiently high for a negative Wigner function confirmed with homodyne measurements. PMID- 27386538 TI - Multiple hot-carrier collection in photo-excited graphene Moire superlattices. AB - In conventional light-harvesting devices, the absorption of a single photon only excites one electron, which sets the standard limit of power-conversion efficiency, such as the Shockley-Queisser limit. In principle, generating and harnessing multiple carriers per absorbed photon can improve efficiency and possibly overcome this limit. We report the observation of multiple hot-carrier collection in graphene/boron-nitride Moire superlattice structures. A record-high zero-bias photoresponsivity of 0.3 A/W (equivalently, an external quantum efficiency exceeding 50%) is achieved using graphene's photo-Nernst effect, which demonstrates a collection of at least five carriers per absorbed photon. We reveal that this effect arises from the enhanced Nernst coefficient through Lifshtiz transition at low-energy Van Hove singularities, which is an emergent phenomenon due to the formation of Moire minibands. Our observation points to a new means for extremely efficient and flexible optoelectronics based on van der Waals heterostructures. PMID- 27386539 TI - Representing higher-order dependencies in networks. AB - To ensure the correctness of network analysis methods, the network (as the input) has to be a sufficiently accurate representation of the underlying data. However, when representing sequential data from complex systems, such as global shipping traffic or Web clickstream traffic as networks, conventional network representations that implicitly assume the Markov property (first-order dependency) can quickly become limiting. This assumption holds that, when movements are simulated on the network, the next movement depends only on the current node, discounting the fact that the movement may depend on several previous steps. However, we show that data derived from many complex systems can show up to fifth-order dependencies. In these cases, the oversimplifying assumption of the first-order network representation can lead to inaccurate network analysis results. To address this problem, we propose the higher-order network (HON) representation that can discover and embed variable orders of dependencies in a network representation. Through a comprehensive empirical evaluation and analysis, we establish several desirable characteristics of HON, including accuracy, scalability, and direct compatibility with the existing suite of network analysis methods. We illustrate how HON can be applied to a broad variety of tasks, such as random walking, clustering, and ranking, and we demonstrate that, by using it as input, HON yields more accurate results without any modification to these tasks. PMID- 27386540 TI - Arrays of microscopic organic LEDs for high-resolution optogenetics. AB - Optogenetics is a paradigm-changing new method to study and manipulate the behavior of cells with light. Following major advances of the used genetic constructs over the last decade, the light sources required for optogenetic control are now receiving increased attention. We report a novel optogenetic illumination platform based on high-density arrays of microscopic organic light emitting diodes (OLEDs). Because of the small dimensions of each array element (6 * 9 MUm(2)) and the use of ultrathin device encapsulation, these arrays enable illumination of cells with unprecedented spatiotemporal resolution. We show that adherent eukaryotic cells readily proliferate on these arrays, and we demonstrate specific light-induced control of the ionic current across the membrane of individual live cells expressing different optogenetic constructs. Our work paves the way for the use of OLEDs for cell-specific optogenetic control in cultured neuronal networks and for acute brain slices, or as implants in vivo. PMID- 27386542 TI - Biomimetic gyroid nanostructures exceeding their natural origins. AB - Using optical two-beam lithography with improved resolution and enhanced mechanical strength, we demonstrate the replication of gyroid photonic nanostructures found in the butterfly Callophrys rubi. These artificial structures are shown to have size, controllability, and uniformity that are superior to those of their biological counterparts. In particular, the elastic Young's modulus of fabricated nanowires is enhanced by up to 20%. As such, the circular dichroism enabled by the gyroid nanostructures can operate in the near ultraviolet wavelength region, shorter than that supported by the natural butterfly wings of C. rubi. This fabrication technique provides a unique tool for extracting three-dimensional photonic designs from nature and will aid the investigation of biomimetic nanostructures. PMID- 27386541 TI - Remarkable enhancement of charge carrier mobility of conjugated polymer field effect transistors upon incorporating an ionic additive. AB - Organic semiconductors with high charge carrier mobilities are crucial for flexible electronic applications. Apart from designing new conjugated frameworks, different strategies have been explored to increase charge carrier mobilities. We report a new and simple approach to enhancing the charge carrier mobility of DPP thieno[3,2-b]thiophene-conjugated polymer by incorporating an ionic additive, tetramethylammonium iodide, without extra treatments into the polymer. The resulting thin films exhibit a very high hole mobility, which is higher by a factor of 24 than that of thin films without the ionic additive under the same conditions. On the basis of spectroscopic grazing incidence wide-angle x-ray scattering and atomic force microscopy studies as well as theoretical calculations, the remarkable enhancement of charge mobility upon addition of tetramethylammonium iodide is attributed primarily to an inhibition of the torsion of the alkyl side chains by the presence of the ionic species, facilitating a more ordered lamellar packing of the alkyl side chains and interchain pi-pi interactions. PMID- 27386543 TI - Proton conductivity in ampullae of Lorenzini jelly. AB - In 1678, Stefano Lorenzini first described a network of organs of unknown function in the torpedo ray-the ampullae of Lorenzini (AoL). An individual ampulla consists of a pore on the skin that is open to the environment, a canal containing a jelly and leading to an alveolus with a series of electrosensing cells. The role of the AoL remained a mystery for almost 300 years until research demonstrated that skates, sharks, and rays detect very weak electric fields produced by a potential prey. The AoL jelly likely contributes to this electrosensing function, yet the exact details of this contribution remain unclear. We measure the proton conductivity of the AoL jelly extracted from skates and sharks. The room-temperature proton conductivity of the AoL jelly is very high at 2 +/- 1 mS/cm. This conductivity is only 40-fold lower than the current state-of-the-art proton-conducting polymer Nafion, and it is the highest reported for a biological material so far. We suggest that keratan sulfate, identified previously in the AoL jelly and confirmed here, may contribute to the high proton conductivity of the AoL jelly with its sulfate groups-acid groups and proton donors. We hope that the observed high proton conductivity of the AoL jelly may contribute to future studies of the AoL function. PMID- 27386544 TI - Rapid oxygenation of Earth's atmosphere 2.33 billion years ago. AB - Molecular oxygen (O2) is, and has been, a primary driver of biological evolution and shapes the contemporary landscape of Earth's biogeochemical cycles. Although "whiffs" of oxygen have been documented in the Archean atmosphere, substantial O2 did not accumulate irreversibly until the Early Paleoproterozoic, during what has been termed the Great Oxygenation Event (GOE). The timing of the GOE and the rate at which this oxygenation took place have been poorly constrained until now. We report the transition (that is, from being mass-independent to becoming mass dependent) in multiple sulfur isotope signals of diagenetic pyrite in a continuous sedimentary sequence in three coeval drill cores in the Transvaal Supergroup, South Africa. These data precisely constrain the GOE to 2.33 billion years ago. The new data suggest that the oxygenation occurred rapidly-within 1 to 10 million years-and was followed by a slower rise in the ocean sulfate inventory. Our data indicate that a climate perturbation predated the GOE, whereas the relationships among GOE, "Snowball Earth" glaciation, and biogeochemical cycling will require further stratigraphic correlation supported with precise chronologies and paleolatitude reconstructions. PMID- 27386545 TI - Hydrogen atoms can be located accurately and precisely by x-ray crystallography. AB - Precise and accurate structural information on hydrogen atoms is crucial to the study of energies of interactions important for crystal engineering, materials science, medicine, and pharmacy, and to the estimation of physical and chemical properties in solids. However, hydrogen atoms only scatter x-radiation weakly, so x-rays have not been used routinely to locate them accurately. Textbooks and teaching classes still emphasize that hydrogen atoms cannot be located with x rays close to heavy elements; instead, neutron diffraction is needed. We show that, contrary to widespread expectation, hydrogen atoms can be located very accurately using x-ray diffraction, yielding bond lengths involving hydrogen atoms (A-H) that are in agreement with results from neutron diffraction mostly within a single standard deviation. The precision of the determination is also comparable between x-ray and neutron diffraction results. This has been achieved at resolutions as low as 0.8 A using Hirshfeld atom refinement (HAR). We have applied HAR to 81 crystal structures of organic molecules and compared the A-H bond lengths with those from neutron measurements for A-H bonds sorted into bonds of the same class. We further show in a selection of inorganic compounds that hydrogen atoms can be located in bridging positions and close to heavy transition metals accurately and precisely. We anticipate that, in the future, conventional x-radiation sources at in-house diffractometers can be used routinely for locating hydrogen atoms in small molecules accurately instead of large-scale facilities such as spallation sources or nuclear reactors. PMID- 27386548 TI - Experimental evidence supports mantle partial melting in the asthenosphere. AB - The low-velocity zone (LVZ) is a persistent seismic feature in a broad range of geological contexts. It coincides in depth with the asthenosphere, a mantle region of lowered viscosity that may be essential to enabling plate motions. The LVZ has been proposed to originate from either partial melting or a change in the rheological properties of solid mantle minerals. The two scenarios imply drastically distinct physical and geochemical states, leading to fundamentally different conclusions on the dynamics of plate tectonics. We report in situ ultrasonic velocity measurements on a series of partially molten samples, composed of mixtures of olivine plus 0.1 to 4.0 volume % of basalt, under conditions relevant to the LVZ. Our measurements provide direct compressional (V P) and shear (V S) wave velocities and constrain attenuation as a function of melt fraction. Mantle partial melting appears to be a viable origin for the LVZ, for melt fractions as low as ~0.2%. In contrast, the presence of volatile elements appears necessary to explaining the extremely high V P/V S values observed in some local areas. The presence of melt in LVZ could play a major role in the dynamics of plate tectonics, favoring the decoupling of the plate relative to the asthenosphere. PMID- 27386547 TI - Structural basis for regulation of human calcium-sensing receptor by magnesium ions and an unexpected tryptophan derivative co-agonist. AB - Ca(2+)-sensing receptors (CaSRs) modulate calcium and magnesium homeostasis and many (patho)physiological processes by responding to extracellular stimuli, including divalent cations and amino acids. We report the first crystal structure of the extracellular domain (ECD) of human CaSR bound with Mg(2+) and a tryptophan derivative ligand at 2.1 A. The structure reveals key determinants for cooperative activation by metal ions and aromatic amino acids. The unexpected tryptophan derivative was bound in the hinge region between two globular ECD subdomains, and represents a novel high-affinity co-agonist of CaSR. The dissection of structure-function relations by mutagenesis, biochemical, and functional studies provides insights into the molecular basis of human diseases arising from CaSR mutations. The data also provide a novel paradigm for understanding the mechanism of CaSR-mediated signaling that is likely shared by the other family C GPCR [G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor] members and can facilitate the development of novel CaSR-based therapeutics. PMID- 27386549 TI - Anticyclonic eddies are more productive than cyclonic eddies in subtropical gyres because of winter mixing. AB - Mesoscale eddies are ubiquitous features of ocean circulation that modulate the supply of nutrients to the upper sunlit ocean, influencing the rates of carbon fixation and export. The popular eddy-pumping paradigm implies that nutrient fluxes are enhanced in cyclonic eddies because of upwelling inside the eddy, leading to higher phytoplankton production. We show that this view does not hold for a substantial portion of eddies within oceanic subtropical gyres, the largest ecosystems in the ocean. Using space-based measurements and a global biogeochemical model, we demonstrate that during winter when subtropical eddies are most productive, there is increased chlorophyll in anticyclones compared with cyclones in all subtropical gyres (by 3.6 to 16.7% for the five basins). The model suggests that this is a consequence of the modulation of winter mixing by eddies. These results establish a new paradigm for anticyclonic eddies in subtropical gyres and could have important implications for the biological carbon pump and the global carbon cycle. PMID- 27386546 TI - Fundamentals of cancer metabolism. AB - Tumors reprogram pathways of nutrient acquisition and metabolism to meet the bioenergetic, biosynthetic, and redox demands of malignant cells. These reprogrammed activities are now recognized as hallmarks of cancer, and recent work has uncovered remarkable flexibility in the specific pathways activated by tumor cells to support these key functions. In this perspective, we provide a conceptual framework to understand how and why metabolic reprogramming occurs in tumor cells, and the mechanisms linking altered metabolism to tumorigenesis and metastasis. Understanding these concepts will progressively support the development of new strategies to treat human cancer. PMID- 27386550 TI - Prebiotic chemicals-amino acid and phosphorus-in the coma of comet 67P/Churyumov Gerasimenko. AB - The importance of comets for the origin of life on Earth has been advocated for many decades. Amino acids are key ingredients in chemistry, leading to life as we know it. Many primitive meteorites contain amino acids, and it is generally believed that these are formed by aqueous alterations. In the collector aerogel and foil samples of the Stardust mission after the flyby at comet Wild 2, the simplest form of amino acids, glycine, has been found together with precursor molecules methylamine and ethylamine. Because of contamination issues of the samples, a cometary origin was deduced from the (13)C isotopic signature. We report the presence of volatile glycine accompanied by methylamine and ethylamine in the coma of 67P/Churyumov-Gerasimenko measured by the ROSINA (Rosetta Orbiter Spectrometer for Ion and Neutral Analysis) mass spectrometer, confirming the Stardust results. Together with the detection of phosphorus and a multitude of organic molecules, this result demonstrates that comets could have played a crucial role in the emergence of life on Earth. PMID- 27386552 TI - Oxyhalides: A new class of high-T C multiferroic materials. AB - Magnetoelectric multiferroics have attracted enormous attention in the past years because of their high potential for applications in electronic devices, which arises from the intrinsic coupling between magnetic and ferroelectric ordering parameters. The initial finding in TbMnO3 has triggered the search for other multiferroics with higher ordering temperatures and strong magnetoelectric coupling for applications. To date, spin-driven multiferroicity is found mainly in oxides, as well as in a few halogenides. We report multiferroic properties for synthetic melanothallite Cu2OCl2, which is the first discovery of multiferroicity in a transition metal oxyhalide. Measurements of pyrocurrent and the dielectric constant in Cu2OCl2 reveal ferroelectricity below the Neel temperature of ~70 K. Thus, melanothallite belongs to a new class of multiferroic materials with an exceptionally high critical temperature. Powder neutron diffraction measurements reveal an incommensurate magnetic structure below T N, and all magnetic reflections can be indexed with a propagation vector [0.827(7), 0, 0], thus discarding the claimed pyrochlore-like "all-in-all-out" spin structure for Cu2OCl2, and indicating that this transition metal oxyhalide is, indeed, a spin induced multiferroic material. PMID- 27386551 TI - Tumor-homing peptides as tools for targeted delivery of payloads to the placenta. AB - The availability of therapeutics to treat pregnancy complications is severely lacking mainly because of the risk of causing harm to the fetus. As enhancement of placental growth and function can alleviate maternal symptoms and improve fetal growth in animal models, we have developed a method for targeted delivery of payloads to the placenta. We show that the tumor-homing peptide sequences CGKRK and iRGD bind selectively to the placental surface of humans and mice and do not interfere with normal development. Peptide-coated nanoparticles intravenously injected into pregnant mice accumulated within the mouse placenta, whereas control nanoparticles exhibited reduced binding and/or fetal transfer. We used targeted liposomes to efficiently deliver cargoes of carboxyfluorescein and insulin-like growth factor 2 to the mouse placenta; the latter significantly increased mean placental weight when administered to healthy animals and significantly improved fetal weight distribution in a well-characterized model of fetal growth restriction. These data provide proof of principle for targeted delivery of drugs to the placenta and provide a novel platform for the development of placenta-specific therapeutics. PMID- 27386553 TI - Pre-Clovis occupation 14,550 years ago at the Page-Ladson site, Florida, and the peopling of the Americas. AB - Stone tools and mastodon bones occur in an undisturbed geological context at the Page-Ladson site, Florida. Seventy-one radiocarbon ages show that ~14,550 calendar years ago (cal yr B.P.), people butchered or scavenged a mastodon next to a pond in a bedrock sinkhole within the Aucilla River. This occupation surface was buried by ~4 m of sediment during the late Pleistocene marine transgression, which also left the site submerged. Sporormiella and other proxy evidence from the sediments indicate that hunter-gatherers along the Gulf Coastal Plain coexisted with and utilized megafauna for ~2000 years before these animals became extinct at ~12,600 cal yr B.P. Page-Ladson expands our understanding of the earliest colonizers of the Americas and human-megafauna interaction before extinction. PMID- 27386554 TI - Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles. AB - Encapsulation of therapeutic molecules within polymer particles is a well established method for achieving controlled release, yet challenges such as low loading, poor encapsulation efficiency, and loss of protein activity limit clinical translation. Despite this, the paradigm for the use of polymer particles in drug delivery has remained essentially unchanged for several decades. By taking advantage of the adsorption of protein therapeutics to poly(lactic-co glycolic acid) (PLGA) nanoparticles, we demonstrate controlled release without encapsulation. In fact, we obtain identical, burst-free, extended-release profiles for three different protein therapeutics with and without encapsulation in PLGA nanoparticles embedded within a hydrogel. Using both positively and negatively charged proteins, we show that short-range electrostatic interactions between the proteins and the PLGA nanoparticles are the underlying mechanism for controlled release. Moreover, we demonstrate tunable release by modifying nanoparticle concentration, nanoparticle size, or environmental pH. These new insights obviate the need for encapsulation and offer promising, translatable strategies for a more effective delivery of therapeutic biomolecules. PMID- 27386555 TI - Enhanced economic connectivity to foster heat stress-related losses. AB - Assessing global impacts of unexpected meteorological events in an increasingly connected world economy is important for estimating the costs of climate change. We show that since the beginning of the 21st century, the structural evolution of the global supply network has been such as to foster an increase of climate related production losses. We compute first- and higher-order losses from heat stress-induced reductions in productivity under changing economic and climatic conditions between 1991 and 2011. Since 2001, the economic connectivity has augmented in such a way as to facilitate the cascading of production loss. The influence of this structural change has dominated over the effect of the comparably weak climate warming during this decade. Thus, particularly under future warming, the intensification of international trade has the potential to amplify climate losses if no adaptation measures are taken. PMID- 27386556 TI - Organic core-sheath nanowire artificial synapses with femtojoule energy consumption. AB - Emulation of biological synapses is an important step toward construction of large-scale brain-inspired electronics. Despite remarkable progress in emulating synaptic functions, current synaptic devices still consume energy that is orders of magnitude greater than do biological synapses (~10 fJ per synaptic event). Reduction of energy consumption of artificial synapses remains a difficult challenge. We report organic nanowire (ONW) synaptic transistors (STs) that emulate the important working principles of a biological synapse. The ONWs emulate the morphology of nerve fibers. With a core-sheath-structured ONW active channel and a well-confined 300-nm channel length obtained using ONW lithography, ~1.23 fJ per synaptic event for individual ONW was attained, which rivals that of biological synapses. The ONW STs provide a significant step toward realizing low energy-consuming artificial intelligent electronics and open new approaches to assembling soft neuromorphic systems with nanometer feature size. PMID- 27386558 TI - Global warming without global mean precipitation increase? AB - Global climate models simulate a robust increase of global mean precipitation of about 1.5 to 2% per kelvin surface warming in response to greenhouse gas (GHG) forcing. Here, it is shown that the sensitivity to aerosol cooling is robust as well, albeit roughly twice as large. This larger sensitivity is consistent with energy budget arguments. At the same time, it is still considerably lower than the 6.5 to 7% K(-1) decrease of the water vapor concentration with cooling from anthropogenic aerosol because the water vapor radiative feedback lowers the hydrological sensitivity to anthropogenic forcings. When GHG and aerosol forcings are combined, the climate models with a realistic 20th century warming indicate that the global mean precipitation increase due to GHG warming has, until recently, been completely masked by aerosol drying. This explains the apparent lack of sensitivity of the global mean precipitation to the net global warming recently found in observations. As the importance of GHG warming increases in the future, a clear signal will emerge. PMID- 27386557 TI - Edge-selenated graphene nanoplatelets as durable metal-free catalysts for iodine reduction reaction in dye-sensitized solar cells. AB - Metal-free carbon-based electrocatalysts for dye-sensitized solar cells (DSSCs) are sufficiently active in Co(II)/Co(III) electrolytes but are not satisfactory in the most commonly used iodide/triiodide (I(-)/I3 (-)) electrolytes. Thus, developing active and stable metal-free electrocatalysts in both electrolytes is one of the most important issues in DSSC research. We report the synthesis of edge-selenated graphene nanoplatelets (SeGnPs) prepared by a simple mechanochemical reaction between graphite and selenium (Se) powders, and their application to the counter electrode (CE) for DSSCs in both I(-)/I3 (-) and Co(II)/Co(III) electrolytes. The edge-selective doping and the preservation of the pristine graphene basal plane in the SeGnPs were confirmed by various analytical techniques, including atomic-resolution transmission electron microscopy. Tested as the DSSC CE in both Co(bpy)3 (2+/3+) (bpy = 2,2' bipyridine) and I(-)/I3 (-) electrolytes, the SeGnP-CEs exhibited outstanding electrocatalytic performance with ultimately high stability. The SeGnP-CE-based DSSCs displayed a higher photovoltaic performance than did the Pt-CE-based DSSCs in both SM315 sensitizer with Co(bpy)3 (2+/3+) and N719 sensitizer with I(-)/I3 ( ) electrolytes. Furthermore, the I3 (-) reduction mechanism, which has not been fully understood in carbon-based CE materials to date, was clarified by an electrochemical kinetics study combined with density functional theory and nonequilibrium Green's function calculations. PMID- 27386559 TI - Efficient and selective degradation of polyethylenes into liquid fuels and waxes under mild conditions. AB - Polyethylene (PE) is the largest-volume synthetic polymer, and its chemical inertness makes its degradation by low-energy processes a challenging problem. We report a tandem catalytic cross alkane metathesis method for highly efficient degradation of polyethylenes under mild conditions. With the use of widely available, low-value, short alkanes (for example, petroleum ethers) as cross metathesis partners, different types of polyethylenes with various molecular weights undergo complete conversion into useful liquid fuels and waxes. This method shows excellent selectivity for linear alkane formation, and the degradation product distribution (liquid fuels versus waxes) can be controlled by the catalyst structure and reaction time. In addition, the catalysts are compatible with various polyolefin additives; therefore, common plastic wastes, such as postconsumer polyethylene bottles, bags, and films could be converted into valuable chemical feedstocks without any pretreatment. PMID- 27386560 TI - A highly shape-adaptive, stretchable design based on conductive liquid for energy harvesting and self-powered biomechanical monitoring. AB - The rapid growth of deformable and stretchable electronics calls for a deformable and stretchable power source. We report a scalable approach for energy harvesters and self-powered sensors that can be highly deformable and stretchable. With conductive liquid contained in a polymer cover, a shape-adaptive triboelectric nanogenerator (saTENG) unit can effectively harvest energy in various working modes. The saTENG can maintain its performance under a strain of as large as 300%. The saTENG is so flexible that it can be conformed to any three-dimensional and curvilinear surface. We demonstrate applications of the saTENG as a wearable power source and self-powered sensor to monitor biomechanical motion. A bracelet like saTENG worn on the wrist can light up more than 80 light-emitting diodes. Owing to the highly scalable manufacturing process, the saTENG can be easily applied for large-area energy harvesting. In addition, the saTENG can be extended to extract energy from mechanical motion using flowing water as the electrode. This approach provides a new prospect for deformable and stretchable power sources, as well as self-powered sensors, and has potential applications in various areas such as robotics, biomechanics, physiology, kinesiology, and entertainment. PMID- 27386561 TI - Dopamine D1 signaling organizes network dynamics underlying working memory. AB - Local prefrontal dopamine signaling supports working memory by tuning pyramidal neurons to task-relevant stimuli. Enabled by simultaneous positron emission tomography-magnetic resonance imaging (PET-MRI), we determined whether neuromodulatory effects of dopamine scale to the level of cortical networks and coordinate their interplay during working memory. Among network territories, mean cortical D1 receptor densities differed substantially but were strongly interrelated, suggesting cross-network regulation. Indeed, mean cortical D1 density predicted working memory-emergent decoupling of the frontoparietal and default networks, which respectively manage task-related and internal stimuli. In contrast, striatal D1 predicted opposing effects within these two networks but no between-network effects. These findings specifically link cortical dopamine signaling to network crosstalk that redirects cognitive resources to working memory, echoing neuromodulatory effects of D1 signaling on the level of cortical microcircuits. PMID- 27386564 TI - Women's connectivity in extreme networks. AB - A popular stereotype is that women will play more minor roles than men as environments become more dangerous and aggressive. Our analysis of new longitudinal data sets from offline and online operational networks [for example, ISIS (Islamic State)] shows that although men dominate numerically, women emerge with superior network connectivity that can benefit the underlying system's robustness and survival. Our observations suggest new female-centric approaches that could be used to affect such networks. They also raise questions about how individual contributions in high-pressure systems are evaluated. PMID- 27386563 TI - Synergistic roles of climate warming and human occupation in Patagonian megafaunal extinctions during the Last Deglaciation. AB - The causes of Late Pleistocene megafaunal extinctions (60,000 to 11,650 years ago, hereafter 60 to 11.65 ka) remain contentious, with major phases coinciding with both human arrival and climate change around the world. The Americas provide a unique opportunity to disentangle these factors as human colonization took place over a narrow time frame (~15 to 14.6 ka) but during contrasting temperature trends across each continent. Unfortunately, limited data sets in South America have so far precluded detailed comparison. We analyze genetic and radiocarbon data from 89 and 71 Patagonian megafaunal bones, respectively, more than doubling the high-quality Pleistocene megafaunal radiocarbon data sets from the region. We identify a narrow megafaunal extinction phase 12,280 +/- 110 years ago, some 1 to 3 thousand years after initial human presence in the area. Although humans arrived immediately prior to a cold phase, the Antarctic Cold Reversal stadial, megafaunal extinctions did not occur until the stadial finished and the subsequent warming phase commenced some 1 to 3 thousand years later. The increased resolution provided by the Patagonian material reveals that the sequence of climate and extinction events in North and South America were temporally inverted, but in both cases, megafaunal extinctions did not occur until human presence and climate warming coincided. Overall, metapopulation processes involving subpopulation connectivity on a continental scale appear to have been critical for megafaunal species survival of both climate change and human impacts. PMID- 27386565 TI - Efficient solar-driven water splitting by nanocone BiVO4-perovskite tandem cells. AB - Bismuth vanadate (BiVO4) has been widely regarded as a promising photoanode material for photoelectrochemical (PEC) water splitting because of its low cost, its high stability against photocorrosion, and its relatively narrow band gap of 2.4 eV. However, the achieved performance of the BiVO4 photoanode remains unsatisfactory to date because its short carrier diffusion length restricts the total thickness of the BiVO4 film required for sufficient light absorption. We addressed the issue by deposition of nanoporous Mo-doped BiVO4 (Mo:BiVO4) on an engineered cone-shaped nanostructure, in which the Mo:BiVO4 layer with a larger effective thickness maintains highly efficient charge separation and high light absorption capability, which can be further enhanced by multiple light scattering in the nanocone structure. As a result, the nanocone/Mo:BiVO4/Fe(Ni)OOH photoanode exhibits a high water-splitting photocurrent of 5.82 +/- 0.36 mA cm( 2) at 1.23 V versus the reversible hydrogen electrode under 1-sun illumination. We also demonstrate that the PEC cell in tandem with a single perovskite solar cell exhibits unassisted water splitting with a solar-to-hydrogen conversion efficiency of up to 6.2%. PMID- 27386562 TI - Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation. AB - We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis. PMID- 27386566 TI - Waveguide metatronics: Lumped circuitry based on structural dispersion. AB - Engineering optical nanocircuits by exploiting modularization concepts and methods inherited from electronics may lead to multiple innovations in optical information processing at the nanoscale. We introduce the concept of "waveguide metatronics," an advanced form of optical metatronics that uses structural dispersion in waveguides to obtain the materials and structures required to construct this class of circuitry. Using numerical simulations, we demonstrate that the design of a metatronic circuit can be carried out by using a waveguide filled with materials with positive permittivity. This includes the implementation of all "lumped" circuit elements and their assembly in a single circuit board. In doing so, we extend the concepts of optical metatronics to frequency ranges where there are no natural plasmonic materials available. The proposed methodology could be exploited as a platform to experimentally validate optical metatronic circuits in other frequency regimes, such as microwave frequency setups, and/or to provide a new route to design optical nanocircuitry. PMID- 27386567 TI - Interfacial gauge methods for incompressible fluid dynamics. AB - Designing numerical methods for incompressible fluid flow involving moving interfaces, for example, in the computational modeling of bubble dynamics, swimming organisms, or surface waves, presents challenges due to the coupling of interfacial forces with incompressibility constraints. A class of methods, denoted interfacial gauge methods, is introduced for computing solutions to the corresponding incompressible Navier-Stokes equations. These methods use a type of "gauge freedom" to reduce the numerical coupling between fluid velocity, pressure, and interface position, allowing high-order accurate numerical methods to be developed more easily. Making use of an implicit mesh discontinuous Galerkin framework, developed in tandem with this work, high-order results are demonstrated, including surface tension dynamics in which fluid velocity, pressure, and interface geometry are computed with fourth-order spatial accuracy in the maximum norm. Applications are demonstrated with two-phase fluid flow displaying fine-scaled capillary wave dynamics, rigid body fluid-structure interaction, and a fluid-jet free surface flow problem exhibiting vortex shedding induced by a type of Plateau-Rayleigh instability. The developed methods can be generalized to other types of interfacial flow and facilitate precise computation of complex fluid interface phenomena. PMID- 27386568 TI - Debris-carrying camouflage among diverse lineages of Cretaceous insects. AB - Insects have evolved diverse methods of camouflage that have played an important role in their evolutionary success. Debris-carrying, a behavior of actively harvesting and carrying exogenous materials, is among the most fascinating and complex behaviors because it requires not only an ability to recognize, collect, and carry materials but also evolutionary adaptations in related morphological characteristics. However, the fossil record of such behavior is extremely scarce, and only a single Mesozoic example from Spanish amber has been recorded; therefore, little is known about the early evolution of this complicated behavior and its underlying anatomy. We report a diverse insect assemblage of exceptionally preserved debris carriers from Cretaceous Burmese, French, and Lebanese ambers, including the earliest known chrysopoid larvae (green lacewings), myrmeleontoid larvae (split-footed lacewings and owlflies), and reduviids (assassin bugs). These ancient insects used a variety of debris material, including insect exoskeletons, sand grains, soil dust, leaf trichomes of gleicheniacean ferns, wood fibers, and other vegetal debris. They convergently evolved their debris-carrying behavior through multiple pathways, which expressed a high degree of evolutionary plasticity. We demonstrate that the behavioral repertoire, which is associated with considerable morphological adaptations, was already widespread among insects by at least the Mid-Cretaceous. Together with the previously known Spanish specimen, these fossils are the oldest direct evidence of camouflaging behavior in the fossil record. Our findings provide a novel insight into early evolution of camouflage in insects and ancient ecological associations among plants and insects. PMID- 27386570 TI - Gravel-bed river floodplains are the ecological nexus of glaciated mountain landscapes. AB - Gravel-bed river floodplains in mountain landscapes disproportionately concentrate diverse habitats, nutrient cycling, productivity of biota, and species interactions. Although stream ecologists know that river channel and floodplain habitats used by aquatic organisms are maintained by hydrologic regimes that mobilize gravel-bed sediments, terrestrial ecologists have largely been unaware of the importance of floodplain structures and processes to the life requirements of a wide variety of species. We provide insight into gravel-bed rivers as the ecological nexus of glaciated mountain landscapes. We show why gravel-bed river floodplains are the primary arena where interactions take place among aquatic, avian, and terrestrial species from microbes to grizzly bears and provide essential connectivity as corridors for movement for both aquatic and terrestrial species. Paradoxically, gravel-bed river floodplains are also disproportionately unprotected where human developments are concentrated. Structural modifications to floodplains such as roads, railways, and housing and hydrologic-altering hydroelectric or water storage dams have severe impacts to floodplain habitat diversity and productivity, restrict local and regional connectivity, and reduce the resilience of both aquatic and terrestrial species, including adaptation to climate change. To be effective, conservation efforts in glaciated mountain landscapes intended to benefit the widest variety of organisms need a paradigm shift that has gravel-bed rivers and their floodplains as the central focus and that prioritizes the maintenance or restoration of the intact structure and processes of these critically important systems throughout their length and breadth. PMID- 27386569 TI - Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer. AB - The functional role of progesterone receptor (PR) and its impact on estrogen signaling in breast cancer remain controversial. In primary ER(+) (estrogen receptor-positive)/PR(+) human tumors, we report that PR reprograms estrogen signaling as a genomic agonist and a phenotypic antagonist. In isolation, estrogen and progestin act as genomic agonists by regulating the expression of common target genes in similar directions, but at different levels. Similarly, in isolation, progestin is also a weak phenotypic agonist of estrogen action. However, in the presence of both hormones, progestin behaves as a phenotypic estrogen antagonist. PR remodels nucleosomes to noncompetitively redirect ER genomic binding to distal enhancers enriched for BRCA1 binding motifs and sites that link PR and ER/PR complexes. When both hormones are present, progestin modulates estrogen action, such that responsive transcriptomes, cellular processes, and ER/PR recruitment to genomic sites correlate with those observed with PR alone, but not ER alone. Despite this overall correlation, the transcriptome patterns modulated by dual treatment are sufficiently different from individual treatments, such that antagonism of oncogenic processes is both predicted and observed. Combination therapies using the selective PR modulator/antagonist (SPRM) CDB4124 in combination with tamoxifen elicited 70% cytotoxic tumor regression of T47D tumor xenografts, whereas individual therapies inhibited tumor growth without net regression. Our findings demonstrate that PR redirects ER chromatin binding to antagonize estrogen signaling and that SPRMs can potentiate responses to antiestrogens, suggesting that cotargeting of ER and PR in ER(+)/PR(+) breast cancers should be explored. PMID- 27386571 TI - Ultrasensitive interferometric on-chip microscopy of transparent objects. AB - Light microscopes can detect objects through several physical processes, such as scattering, absorption, and reflection. In transparent objects, these mechanisms are often too weak, and interference effects are more suitable to observe the tiny refractive index variations that produce phase shifts. We propose an on-chip microscope design that exploits birefringence in an unconventional geometry. It makes use of two sheared and quasi-overlapped illuminating beams experiencing relative phase shifts when going through the object, and a complementary metal oxide-semiconductor image sensor array to record the resulting interference pattern. Unlike conventional microscopes, the beams are unfocused, leading to a very large field of view (20 mm(2)) and detection volume (more than 0.5 cm(3)), at the expense of lateral resolution. The high axial sensitivity (<1 nm) achieved using a novel phase-shifting interferometric operation makes the proposed device ideal for examining transparent substrates and reading microarrays of biomarkers. This is demonstrated by detecting nanometer-thick surface modulations on glass and single and double protein layers. PMID- 27386572 TI - The transition from linear to highly branched poly(beta-amino ester)s: Branching matters for gene delivery. AB - Nonviral gene therapy holds great promise but has not delivered treatments for clinical application to date. Lack of safe and efficient gene delivery vectors is the major hurdle. Among nonviral gene delivery vectors, poly(beta-amino ester)s are one of the most versatile candidates because of their wide monomer availability, high polymer flexibility, and superior gene transfection performance both in vitro and in vivo. However, to date, all research has been focused on vectors with a linear structure. A well-accepted view is that dendritic or branched polymers have greater potential as gene delivery vectors because of their three-dimensional structure and multiple terminal groups. Nevertheless, to date, the synthesis of dendritic or branched polymers has been proven to be a well-known challenge. We report the design and synthesis of highly branched poly(beta-amino ester)s (HPAEs) via a one-pot "A2 + B3 + C2"-type Michael addition approach and evaluate their potential as gene delivery vectors. We find that the branched structure can significantly enhance the transfection efficiency of poly(beta-amino ester)s: Up to an 8521-fold enhancement in transfection efficiency was observed across 12 cell types ranging from cell lines, primary cells, to stem cells, over their corresponding linear poly(beta amino ester)s (LPAEs) and the commercial transfection reagents polyethyleneimine, SuperFect, and Lipofectamine 2000. Moreover, we further demonstrate that HPAEs can correct genetic defects in vivo using a recessive dystrophic epidermolysis bullosa graft mouse model. Our findings prove that the A2 + B3 + C2 approach is highly generalizable and flexible for the design and synthesis of HPAEs, which cannot be achieved by the conventional polymerization approach; HPAEs are more efficient vectors in gene transfection than the corresponding LPAEs. This provides valuable insight into the development and applications of nonviral gene delivery and demonstrates great prospect for their translation to a clinical environment. PMID- 27386573 TI - High functional diversity stimulates diversification in experimental microbial communities. AB - There is a growing awareness that biodiversity not only drives ecosystem services but also affects evolutionary dynamics. However, different theories predict contrasting outcomes on when do evolutionary processes occur within a context of competition. We tested whether functional diversity can explain diversification patterns. We tracked the survival and diversification of a focal bacterial species (Pseudomonas fluorescens) growing in bacterial communities of variable diversity and composition. We found that high functional diversity reduced the fitness of the focal species and, at the same time, fostered its diversification. This pattern was linked to resource competition: High diversity increased competition on a portion of the resources while leaving most underexploited. The evolved phenotypes of the focal species showed a better use of underexploited resources, albeit at a cost of lower overall growth rates. As a result, diversification alleviated the impact of competition on the fitness of the focal species. We conclude that biodiversity can stimulate evolutionary diversification, provided that sufficient alternative niches are available. PMID- 27386575 TI - Domain morphology, boundaries, and topological defects in biophotonic gyroid nanostructures of butterfly wing scales. AB - Many organisms in nature have evolved sophisticated cellular mechanisms to produce photonic nanostructures and, in recent years, diverse crystalline symmetries have been identified and related to macroscopic optical properties. However, because we know little about the distributions of domain sizes, the orientations of photonic crystals, and the nature of defects in these structures, we are unable to make the connection between the nanostructure and its development and functionality. We report on nondestructive studies of the morphology of chitinous photonic crystals in butterfly wing scales. Using spatially and angularly resolved x-ray diffraction, we find that the domains are highly oriented with respect to the whole scale, indicating growth from scale boundaries. X-ray coherent diffractive imaging reveals two types of crystalline domain interfaces: abrupt changes between domains emerging from distinct nucleation sites and smooth transitions with edge dislocations presumably resulting from internal stresses during nanostructure development. Our study of the scale structure reveals new aspects of photonic crystal growth in butterfly wings and shows their similarity to block copolymer materials. It opens new avenues to exploration of fundamental processes underlying the growth of biological photonic nanostructures in a variety of species. PMID- 27386574 TI - Oil droplet self-transportation on oleophobic surfaces. AB - Directional liquid transportation is important for a variety of biological processes and technical applications. Although surface engineering through asymmetric chemical modification or geometrical patterning facilitates effective liquid manipulation and enables water droplet self-transportation on synthetic surfaces, self-transportation of oil droplets poses a major challenge because of their low surface tension. We report oil droplet self-transportation on oleophobic surfaces that are microtextured with radial arrays of undercut stripes. More significantly, we observe three modes of oil motion on various sample surfaces, namely, inward transportation, pinned, and outward spreading, which can be switched by the structure parameters, including stripe intersection angle and width. Accompanying theoretical modeling provides an in-depth mechanistic understanding of the structure-droplet motion relationship. Finally, we reveal how to optimize the texture parameters to maximize oil droplet self transportation capability and demonstrate spontaneous droplet movement for liquids down to a surface tension of 22.4 mN/m. The surfaces presented here open up new avenues for power-free liquid transportation and oil contamination self removal applications in various analytical and fluidic devices. PMID- 27386576 TI - A Devonian predatory fish provides insights into the early evolution of modern sarcopterygians. AB - Crown or modern sarcopterygians (coelacanths, lungfishes, and tetrapods) differ substantially from stem sarcopterygians, such as Guiyu and Psarolepis, and a lack of transitional fossil taxa limits our understanding of the origin of the crown group. The Onychodontiformes, an enigmatic Devonian predatory fish group, seems to have characteristics of both stem and crown sarcopterygians but is difficult to place because of insufficient anatomical information. We describe the new skull material of Qingmenodus, a Pragian (~409-million-year-old) onychodont from China, using high-resolution computed tomography to image internal structures of the braincase. In addition to its remarkable similarities with stem sarcopterygians in the ethmosphenoid portion, Qingmenodus exhibits coelacanth like neurocranial features in the otic region. A phylogenetic analysis based on a revised data set unambiguously assigns onychodonts to crown sarcopterygians as stem coelacanths. Qingmenodus thus bridges the morphological gap between stem sarcopterygians and coelacanths and helps to illuminate the early evolution and diversification of crown sarcopterygians. PMID- 27386577 TI - Noninvasive, near-field terahertz imaging of hidden objects using a single-pixel detector. AB - Terahertz (THz) imaging can see through otherwise opaque materials. However, because of the long wavelengths of THz radiation (lambda = 400 MUm at 0.75 THz), far-field THz imaging techniques suffer from low resolution compared to visible wavelengths. We demonstrate noninvasive, near-field THz imaging with subwavelength resolution. We project a time-varying, intense (>100 MUJ/cm(2)) optical pattern onto a silicon wafer, which spatially modulates the transmission of synchronous pulse of THz radiation. An unknown object is placed on the hidden side of the silicon, and the far-field THz transmission corresponding to each mask is recorded by a single-element detector. Knowledge of the patterns and of the corresponding detector signal are combined to give an image of the object. Using this technique, we image a printed circuit board on the underside of a 115 MUm-thick silicon wafer with ~100-MUm (lambda/4) resolution. With subwavelength resolution and the inherent sensitivity to local conductivity, it is possible to detect fissures in the circuitry wiring of a few micrometers in size. THz imaging systems of this type will have other uses too, where noninvasive measurement or imaging of concealed structures is necessary, such as in semiconductor manufacturing or in ex vivo bioimaging. PMID- 27386578 TI - Role of scaffold network in controlling strain and functionalities of nanocomposite films. AB - Strain is a novel approach to manipulating functionalities in correlated complex oxides. However, significant epitaxial strain can only be achieved in ultrathin layers. We show that, under direct lattice matching framework, large and uniform vertical strain up to 2% can be achieved to significantly modify the magnetic anisotropy, magnetism, and magnetotransport properties in heteroepitaxial nanoscaffold films, over a few hundred nanometers in thickness. Comprehensive designing principles of large vertical strain have been proposed. Phase-field simulations not only reveal the strain distribution but also suggest that the ultimate strain is related to the vertical interfacial area and interfacial dislocation density. By changing the nanoscaffold density and dimension, the strain and the magnetic properties can be tuned. The established correlation among the vertical interface-strain-properties in nanoscaffold films can consequently be used to tune other functionalities in a broad range of complex oxide films far beyond critical thickness. PMID- 27386580 TI - Off-axis magmatism along a subaerial back-arc rift: Observations from the Taupo Volcanic Zone, New Zealand. AB - Continental rifting and seafloor spreading play a fundamental role in the generation of new crust. However, the distribution of magma and its relationship with tectonics and volcanism remain poorly understood, particularly in back-arc settings. We show evidence for a large, long-lived, off-axis magmatic intrusion located on the margin of the Taupo Volcanic Zone, New Zealand. Geodetic data acquired since the 1950s show evidence for uplift outside of the region of active extension, consistent with the inflation of a magmatic body at a depth of ~9.5 km. Satellite radar interferometry and Global Positioning System data suggest that there was an increase in the inflation rate from 2003 to 2011, which correlates with intense earthquake activity in the region. Our results suggest that the continued growth of a large magmatic body may represent the birth of a new magma chamber on the margins of a back-arc rift system. PMID- 27386579 TI - Time-gated FRET nanoassemblies for rapid and sensitive intra- and extracellular fluorescence imaging. AB - Time-gated Forster resonance energy transfer (FRET) using the unique material combination of long-lifetime terbium complexes (Tb) and semiconductor quantum dots (QDs) provides many advantages for highly sensitive and multiplexed biosensing. Although time-gated detection can efficiently suppress sample autofluorescence and background fluorescence from directly excited FRET acceptors, Tb-to-QD FRET has rarely been exploited for biomolecular imaging. We demonstrate Tb-to-QD time-gated FRET nanoassemblies that can be applied for intra and extracellular imaging. Immunostaining of different epitopes of the epidermal growth factor receptor (EGFR) with Tb- and QD-conjugated antibodies and nanobodies allowed for efficient Tb-to-QD FRET on A431 cell membranes. The broad usability of Tb-to-QD FRET was further demonstrated by intracellular Tb-to-QD FRET and Tb-to-QD-to-dye FRET using microinjection as well as cell-penetrating peptide-mediated endocytosis with HeLa cells. Effective brightness enhancement by FRET from several Tb to the same QD, the use of low nanomolar concentrations, and the quick and sensitive detection void of FRET acceptor background fluorescence are important advantages for advanced intra- and extracellular imaging of biomolecular interactions. PMID- 27386581 TI - Tuning ice nucleation with counterions on polyelectrolyte brush surfaces. AB - Heterogeneous ice nucleation (HIN) on ionic surfaces is ubiquitous in a wide range of atmospheric aerosols and at biological interfaces. Despite its great importance in cirrus cloud formation and cryopreservation of cells, organs, and tissues, it remains unclear whether the ion-specific effect on ice nucleation exists. Benefiting from the fact that ions at the polyelectrolyte brush (PB)/water interface can be reversibly exchanged, we report the effect of ions on HIN on the PB surface, and we discover that the distinct efficiency of ions in tuning HIN follows the Hofmeister series. Moreover, a large HIN temperature window of up to 7.8 degrees C is demonstrated. By establishing a correlation between the fraction of ice-like water molecules and the kinetics of structural transformation from liquid- to ice-like water molecules at the PB/water interface with different counterions, we show that our molecular dynamics simulation analysis is consistent with the experimental observation of the ion-specific effect on HIN. PMID- 27386582 TI - The new world atlas of artificial night sky brightness. AB - Artificial lights raise night sky luminance, creating the most visible effect of light pollution-artificial skyglow. Despite the increasing interest among scientists in fields such as ecology, astronomy, health care, and land-use planning, light pollution lacks a current quantification of its magnitude on a global scale. To overcome this, we present the world atlas of artificial sky luminance, computed with our light pollution propagation software using new high resolution satellite data and new precision sky brightness measurements. This atlas shows that more than 80% of the world and more than 99% of the U.S. and European populations live under light-polluted skies. The Milky Way is hidden from more than one-third of humanity, including 60% of Europeans and nearly 80% of North Americans. Moreover, 23% of the world's land surfaces between 75 degrees N and 60 degrees S, 88% of Europe, and almost half of the United States experience light-polluted nights. PMID- 27386583 TI - Tunable room-temperature spin-selective optical Stark effect in solution processed layered halide perovskites. AB - Ultrafast spin manipulation for opto-spin logic applications requires material systems that have strong spin-selective light-matter interaction. Conventional inorganic semiconductor nanostructures [for example, epitaxial II to VI quantum dots and III to V multiple quantum wells (MQWs)] are considered forerunners but encounter challenges such as lattice matching and cryogenic cooling requirements. Two-dimensional halide perovskite semiconductors, combining intrinsic tunable MQW structures and large oscillator strengths with facile solution processability, can offer breakthroughs in this area. We demonstrate novel room-temperature, strong ultrafast spin-selective optical Stark effect in solution-processed (C6H4FC2H4NH3)2PbI4 perovskite thin films. Exciton spin states are selectively tuned by ~6.3 meV using circularly polarized optical pulses without any external photonic cavity (that is, corresponding to a Rabi energy of ~55 meV and equivalent to applying a 70 T magnetic field), which is much larger than any conventional system. The facile halide and organic replacement in these perovskites affords control of the dielectric confinement and thus presents a straightforward strategy for tuning light-matter coupling strength. PMID- 27386585 TI - Diverse rupture processes in the 2015 Peru deep earthquake doublet. AB - Earthquakes in deeply subducted oceanic lithosphere can involve either brittle or dissipative ruptures. On 24 November 2015, two deep (606 and 622 km) magnitude 7.5 and 7.6 earthquakes occurred 316 s and 55 km apart. The first event (E1) was a brittle rupture with a sequence of comparable-size subevents extending unilaterally ~50 km southward with a rupture speed of ~4.5 km/s. This earthquake triggered several aftershocks to the north along with the other major event (E2), which had 40% larger seismic moment and the same duration (~20 s), but much smaller rupture area and lower rupture speed than E1, indicating a more dissipative rupture. A minor energy release ~12 s after E1 near the E2 hypocenter, possibly initiated by the S wave from E1, and a clear aftershock ~165 s after E1 also near the E2 hypocenter, suggest that E2 was likely dynamically triggered. Differences in deep earthquake rupture behavior are commonly attributed to variations in thermal state between subduction zones. However, the marked difference in rupture behavior of the nearby Peru doublet events suggests that local variations of stress state and material properties significantly contribute to diverse behavior of deep earthquakes. PMID- 27386586 TI - The Aftermath of the Fukushima Daiichi Accident: a Perspective from the British Embassy in Tokyo. AB - The British Embassy in Tokyo was at the heart of providing information in the immediate aftermath of the Fukushima Daiichi accident. Richard Oppenheim, who was present at the time, and Keith Franklin, who joined the Embassy shortly afterwards, give their perspectives on communicating information on radiation to the public and what lessons can be learned. Richard Oppenheim was head of the Climate Change and Energy team at the British Embassy in Tokyo from 2011 to 2015 and part of the Embassy team responding to the crisis. He travelled to Sendai on 12 March 2011. Keith Franklin has been on secondment to the British Embassy in Tokyo from the National Nuclear Laboratory since the accident at Fukushima Daiichi. PMID- 27386584 TI - Matrix-bound nanovesicles within ECM bioscaffolds. AB - Biologic scaffold materials composed of extracellular matrix (ECM) have been used in a variety of surgical and tissue engineering/regenerative medicine applications and are associated with favorable constructive remodeling properties including angiogenesis, stem cell recruitment, and modulation of macrophage phenotype toward an anti-inflammatory effector cell type. However, the mechanisms by which these events are mediated are largely unknown. Matrix-bound nanovesicles (MBVs) are identified as an integral and functional component of ECM bioscaffolds. Extracellular vesicles (EVs) are potent vehicles of intercellular communication due to their ability to transfer RNA, proteins, enzymes, and lipids, thereby affecting physiologic and pathologic processes. Formerly identified exclusively in biologic fluids, the presence of EVs within the ECM of connective tissue has not been reported. In both laboratory-produced and commercially available biologic scaffolds, MBVs can be separated from the matrix only after enzymatic digestion of the ECM scaffold material, a temporal sequence similar to the functional activity attributed to implanted bioscaffolds during and following their degradation when used in clinical applications. The present study shows that MBVs contain microRNA capable of exerting phenotypical and functional effects on macrophage activation and neuroblastoma cell differentiation. The identification of MBVs embedded within the ECM of biologic scaffolds provides mechanistic insights not only into the inductive properties of ECM bioscaffolds but also into the regulation of tissue homeostasis. PMID- 27386587 TI - Reclaiming Our Lives in the Wake of a Nuclear Plant Accident. AB - Ryoko Ando lives and works in Iwaki-shi, which is located in the coastal area of Fukushima Prefecture. On 11 March 2011, Iwaki was hit by the Great East Japan Earthquake and tsunami. Then the nuclear plant accident at Fukushima No. 1 nuclear power plant, also located in the coastal area of Fukushima Prefecture, added to the woes of Iwaki residents. Although Iwaki-shi is outside of the 'restricted area' set up by the government in the 20 km radius around the nuclear power plant, some municipalities in Iwaki-shi lie within the 30 km radius zone. The residents of Iwaki were naturally concerned about the effects of radioactive contamination. On top of these, they had to confront a wide range of issues, including confusion and miscommunication, reputation risk and infrastructural constraints due to the influx of residents from the 'restricted area'. PMID- 27386588 TI - Clarification: Half-Life of Heroin. PMID- 27386589 TI - [Moyamoya disease]. AB - Moya-moya is a rare cerebrovascular disease characterized by the progressive occlusion of cerebral vessels with partial switching off the circle of Willis and arteries that feed it. The article provides a review of literature, modern diagnostic criteria and a description of a single clinical case. The onset of the disease in this patient was characterized by headache and speech disorders.An analysis of speech disorders showed that they were systemic. They were registered at all language levels (phonetic, lexical,morphological, syntactic). A long diagnostic search may be explained by clinical manifestations that are atypical for other cerebrovascular diseases and by the rarity of the disease. PMID- 27386590 TI - [The etioiogy, pathophysiology and differential diagnosis of benign paroxysmal positional vertigo]. AB - Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vestibular disorder. The confirmation of BPPV is easy and based on a set of positioning tests. The authors present the recent data concerning the-etiology, pathophysiology a:nd the most effective positioning tests for the posterior, horizontal and anterior semicircular canals. The differential diagnosis of BPPV from other diseases, manifesting with positional vertigo, is discussed as well. PMID- 27386591 TI - [A choice of a nonsteroidal anti-inflammatory drug with regard to gastrointestinal and cardiovascular' risks]. AB - NSAIDs are effective drugs among analgesics and antiinflammatory drugs used widely in clinical practice. It is important to emphasize that the range of users of NSAIDs in population are patients with chronic disorders of the joints and spine. However,when prescribing NSAIDs one should consider risk factors of side effects not only from the gastrointestinal tract, but cardiovascular events as well. The potential negative risks of using NSAIDs promote an active research on creation of ne...y medicinal substances which are able to minimize NSAID-induced complications. The use of oxide-nitrogen-associated NSAIDs, in particular amtolmetin guacil1in patients with risk factors of side-effects from the gastrointestinal tract and cardiovascular system seems to be promising.It is noted that amtolmetin guacil has balanced analgesic and anti-inflammatory effects and is well tolerated. PMID- 27386592 TI - [Comorbid states in Parkinson's disease: an effect of MAO-B inhibitors]. AB - The comorbidity in Parkinson's disease (PD), which is closely related to the tolerability of antiparkinsonian drugs, is-'analyzed. The authors present the results of the studies that have confirmed the greater safety of rasagiline compared to dopamine receptor agonists in elderly patients. The effects of rasagiline, including combinations of this drug with antidepressants, on depression in PD and the low risk,of the serotonin -syndrome caused by these combinations are considered. The studies demonstrated the effect of rasagiline on fatigue and cognitive functions in PD patients are described. Single cases of the development of impulsive compulsive disorders:in patients treated with- rasagiline are presented. PMID- 27386593 TI - [Farmacological effects of anti-S 100 in release-active form and mechanisms of their realization]. AB - Antibodies to 5100 proteins (anti-5100) in release-active form (RA anti-5100) are an active component of some domestic drugs(tenoten, tenoten for children, divaza, brizantin, kolofort and proproten-100). The authors present the results of preclinical and clinical trials (with detailed consideration of experimental data) which demonstrated a wide spectrum of specific pharmacological activity and safety as well as mechanisms of anti-5100 action. PMID- 27386594 TI - [Between depression and fibroniyalgia: the fate of the antidepressant]. AB - The authors present the information about one of the least studied antidepressants- milnacipran. Recommendations of its clinical use have been long based on incorrect conceptions of its pharmacological properties. Currently, milnacipran is considered as ancirepinephrine and serotonin (to a lesser degree) reuptake inhibitor and NMDA receptor blocker. Milnacipran can be successfully used in apatic, asthenic, adynamic and anhedonic depressions as well as in fibromyalgia in patients with marked fatigability and pain. However the recommendations for the latter are not registered in Russia (maybe due to the differences in the diagnosis of fibromyalgia which is traditionally more often diagnosed as neurasthenia). PMID- 27386595 TI - [M.A. Piradov (the 60th anniversary of birth)]. PMID- 27386596 TI - [V.S, Goidenko (the 80th anniversary of birth)]. PMID- 27386597 TI - Red cell agglutination in infectious mononucleosis. PMID- 27386598 TI - Editorial. PMID- 27386599 TI - [What is really important]. PMID- 27386600 TI - [The call of the ancestors]. PMID- 27386601 TI - High Doses of Vitamin D Linked to Increased Risk of Falls. PMID- 27386602 TI - Involving Family Members to Reduce Hospital Readmissions. PMID- 27386603 TI - Reading Problems Linked to Possible Alzheimer's Disease Misdiagnosis. PMID- 27386604 TI - Zinc Supplement Boosts Immunity in Older Adults. PMID- 27386605 TI - Strategies for Achieving Measurement Assurance for Cell Therapy Products. AB - The cell therapy industry has identified the inability to reliably characterize cells as possibly its greatest challenge and has called for standards and reference materials to provide assurance for measurements of cell properties. The challenges in characterization of cell therapy products can be largely addressed with systematic approaches for assessing sources of uncertainty and improving confidence in key measurements. This article presents the many strategies that can be used to ensure measurement confidence and discusses them in terms of how they can be applied to characterization of cell therapy products. SIGNIFICANCE: Application of these strategies to cell measurements will help to establish qualified assays for cell characterization, which may help streamline regulatory approval and enable more efficient development of cell therapy products. PMID- 27386606 TI - Genomic Plasticity of Multidrug-Resistant NDM-1 Positive Clinical Isolate of Providencia rettgeri. AB - We performed a detailed whole-genome sequence analysis of Providencia rettgeri H1736, a multidrug-resistant clinical pathogen isolated in Israel in 2011. The objective was to describe the genomic flexibility of this bacterium that has greatly contributed to its pathogenicity. The genome has a chromosome size of 4,609,352 bp with 40.22% GC content. Five plasmids were predicted, as well as other mobile genetic elements (MGEs) including phages, genomic islands, and integrative and conjugative elements. The resistome consisted of a total of 27 different antibiotic resistance genes including blaNDM-1, mostly located on MGEs. Phenotypically, the bacteria displayed resistance to a total of ten different antimicrobial classes. Various features such as metabolic operons (including a novel carbapenem biosynthesis operon) and virulence genes were also borne on the MGEs, making P. rettgeri H1736 significantly different from other P. rettgeri isolates. A large quantity of the genetic diversity that exists in P. rettgeri H1736 was due to extensive horizontal gene transfer events, leading to an enormous presence of MGEs in its genome. Most of these changes contributed toward the pathogenic evolution of this bacterium. PMID- 27386607 TI - Blacklisting: The dirty side of travel nursing. AB - With the dearth of dialysis travel nurses, you can't afford to blacklist one unless it is for a legitimate egregious clinical or professional reason affecting patient care. In a case like that, most reputable staffing agencies would not want to employ the travel nurse either. PMID- 27386609 TI - Top-paid executives at publicly traded healthcare companies. Ranked by total compensation for 2015 as reported to the U.S. Securities and Exchange Commission. PMID- 27386608 TI - Top 30 Medicare Advantage insurers. Ranked by total enrollment in March 2016. PMID- 27386610 TI - Highest-cost metro areas in joint replacement bundled payment program. Ranked by joint replacement cost percentage above the regional average. PMID- 27386618 TI - Announcement: National Kidney Month - March 2016. AB - March is designated National Kidney Month to raise awareness about the prevention and early detection of kidney disease. Approximately 10% (20 million) of U.S. adults aged >=20 years have chronic kidney disease (CKD), and most of them are unaware of their condition. If left untreated, CKD can lead to kidney failure, requiring dialysis or transplantation for survival. PMID- 27386619 TI - In This Issue: Confronting Constraints on Individual Behavior & Outcomes. PMID- 27386620 TI - [Reconstructive investigations and identification measures in unknown soldiers of the Second World War]. AB - The article reports on the exhumation and identification of unknown soldiers from the Second World War. With the help of medicolegal investigation and reconstruction methods an American pilot presumably murdered by a shot to the head (lynch law) and an interned Italian soldier could be identified after about 70 years and brought back home. PMID- 27386621 TI - [Skull fracture or accessory suture in a child?]. AB - Differentiation between accessory sutures and fractures in the skull of an infant can be difficult. Apart from the regular sutures there is a multitude of variations that may be mistaken for a fracture line. Such variations include for instance the intraparietal suture between the two ossification centers of the parietal bone or the mendosal suture between the supraoccipital and interparietal bone of the occipital squama. The presented case refers to an approximately 20 month-old female child. During autopsy, a discontinuity in the right paramedian posterior cranial fossa parallel to the internal occipital crest with connection to the foramen magnum was observed. The macroscopic findings suggested a fracture line because of its course. However, neither a hemorrhage in the soft tissue nor callus formation was discernible. The discontinuity was preserved with the adjacent parts of the occipital bone for further histological examination. In the report of a cranial CT, which was carried out five days before the child's death, an accessory suture paramedially in the right posterior cranial fossa was described. When the clinical CT records were re-evaluated, a similar discontinuity at the corresponding position on the other side was detected, though of noticeably shorter length. Additionally, the preserved occipital bone fragment including the discontinuity was histologically processed. In the radiological literature, precise (radiological) criteria for differential diagnosis are indicated. A zigzag pattern with sclerotic borders and a bilateral and fairly symmetric occurrence indicate a suture, whereas a sharp lucency with non-sclerotic edges and a unilateral occurrence indicate a fracture. Taking all the findings into account, the depicted discontinuity was regarded as an accessory suture. This case demonstrates that differentiation between a fracture and an accessory suture may be difficult in the autopsy of a child and underlines the importance of a postmortem CT examination. PMID- 27386623 TI - [True color accuracy in digital forensic photography]. AB - Forensic photographs not only need to be unaltered and authentic and capture context-relevant images, along with certain minimum requirements for image sharpness and information density, but color accuracy also plays an important role, for instance, in the assessment of injuries or taphonomic stages, or in the identification and evaluation of traces from photos. The perception of color not only varies subjectively from person to person, but as a discrete property of an image, color in digital photos is also to a considerable extent influenced by technical factors such as lighting, acquisition settings, camera, and output medium (print, monitor). For these reasons, consistent color accuracy has so far been limited in digital photography. Because images usually contain a wealth of color information, especially for complex or composite colors or shades of color, and the wavelength-dependent sensitivity to factors such as light and shadow may vary between cameras, the usefulness of issuing general recommendations for camera capture settings is limited. Our results indicate that true image colors can best and most realistically be captured with the SpyderCheckr technical calibration tool for digital cameras tested in this study. Apart from aspects such as the simplicity and quickness of the calibration procedure, a further advantage of the tool is that the results are independent of the camera used and can also be used for the color management of output devices such as monitors and printers. The SpyderCheckr color-code patches allow true colors to be captured more realistically than with a manual white balance tool or an automatic flash. We therefore recommend that the use of a color management tool should be considered for the acquisition of all images that demand high true color accuracy (in particular in the setting of injury documentation). PMID- 27386622 TI - [Sepsis due to fusobacteria in a young adult]. AB - Fusobacteria belong to the normal population of the pharyngeal mucosa as well as the mucosa of the upper airways and the gastrointestinal tract. Infections are comparatively rare. The most common causative organism is Fusobacterium necrophorum. A well-known infection caused by this germ is Lemierre's syndrome. In the presented case, a 19-year-old man (123 kg body weight, 186 cm body length) was found dead in his bed in the morning after having complained of muscular fatigue and vomiting the previous day. Autopsy was carried out only two days after death. At that time, the body showed marked putrefaction with partial greenish discoloration and marbling of the skin although it had been stored in a refrigerator at +2 degrees C in the meantime. While the autopsy itself revealed no cause of death, microbiological examination of a smear from the left lower pulmonary lobe demonstrated Staphylococcus aureus and Fusobacterium necrophorum. Toxicological investigations produced negative results throughout. The cause of death was defined as sepsis caused by Fusobacterium necrophorum. PMID- 27386624 TI - [Stature estimation from sagittal and coronal suture lengths for Central European individuals]. AB - $Human skulls frequently represent the only skeletal remains of an unidentified corpse available for forensic osteological examination. Skulls are very useful in reliably determining sex and also yield fairly good clues to an individual's age and ancestry. To date, however, a sufficiently accurate correlation between skull measurements and stature could not be found. In contrast, the results of a study by Rao et al. (2009) seemed to be promising, by finding a good correlation between the length of the coronal and sagittal sutures and stature in a male Indian population. In an attempt to verify the transferability of their results to a Central European population, the authors measured the length of the sagittal and coronal sutures with a tape measure along with body height in the course of 117 autopsies performed at the Institute of Forensic Medicine at the University of Giessen during 2009 and 2010. The age of the individuals measured ranged from 15 to 96 years (mean value 52.8, median 51 years). Of these individuals, 82 were male and 35 were female. The length of the sagittal suture with respect to body length yielded a correlation coefficient of only r = 0.045 (p = 0.617) in the regression analysis. Similar results were found for the coronal suture: In this case the correlation coefficient was r = 0.015. With an assumed maximum permissible probability of error of alpha = 0.05, none of the performed regression analyses were found to be statistically significant. As expected, our results suggest that neither the length of the sagittal nor the length of the coronal suture is suitable for a forensic estimation of stature for Central European individuals. PMID- 27386625 TI - [An unusual bodily injury]. AB - In most cases, bodily harm results from the use of sharp objects or blunt force. This paper deals with a 42-year-old pharmacist who was known to the police and the courts because of several previous convictions for bodily injury. The man had visited a pub just before it closed and was therefore not served any drinks. He got angry about this and returned to his pharmacy (within walking distance) to fetch three disposable syringes which he filled with phosphoric acid (85%). Through the open pub window, he splattered the acid from the syringes on two guests and the host, who were hit on the upper part of their bodies and the arms. All the victims developed dermal alterations such as focal erythema and small blisters (pemphigus-like efflorescences, as already described by Weyrich). At first, the pharmacist denied the use of phosphoric acid and claimed to have used a mixture of urine and water. Examinations of spots on the still unwashed clothes revealed very low pH-values (ca. 2.0; pH-Indicator-Stripes, Merck; Medi-Test, Machery & Nagel). Tests for substances typical of urine produced completely negative results. However, very high phosphate concentrations were found on the spots in question. Thus, the probability that the pharmacist had used phosphoric acid to commit the offence was very high. The pharmacist was sentenced to one year and two months' imprisonment for dangerous bodily harm according to Section 224 German Criminal Code. In accordance with the law, phosphoric acid was classified as "poison", for which application on the skin is sufficient. PMID- 27386626 TI - Automated Region-based Prostate Cancer Cell Nuclei Localization. Part of a Prognostic Modality Tool for Prostate Cancer Patients. AB - BACKGROUND: Prostate cancer is a disease of disrupted cell genomes. Quantification of DNA from cytology preparations can yield prognostic information about tissue biological behaviors; however, this process is very labor-intensive to perform. Quantitative digital pathology can measure the structural chromatin changes associated with neoplasia and can enable prognostic and predictive assays based on imaging of sectioned prostate tissue. OBJECTIVE: To design an automated system to recognize and localize cell nuclei in images of stained sectioned tissue (first step in enabling quantitative digital pathology). STUDY DESIGN: Images of Feulgen-thionin-stained prostate cancer tissue microarray constructed from the surgical specimens of 33 prostate cancer patients were acquired for this study. We implemented a new image segmentation technique to overcome tissue complexity, cell clusters, background noise, image and tissue inhomogeneities, and other imaging issues that introduce uncertainties into the segmentation method and developed a fully automated system to localized prostate cell nuclei. RESULTS: We applied our algorithm on our dataset and obtained a 96.6% true positive rate and a 12% false-positive rate. CONCLUSION: In this paper we present a new method to automatically localize thionin-stained prostate cancer cells, enabling the extraction of various nuclear and cell sociology features with high precision. PMID- 27386627 TI - Distribution and Developmental Changes of Neuropeptide Y and Its Y1 Receptor-like Immunoreactive Cells in the Duck Thymus. AB - OBJECTIVE: To investigate the distribution and developmental changes of Neuropeptide-Y (NPY) and its Y1 receptor (NPYY1)-like immunoreactivity cells in the duck thymus using immunohistochemistry associated with morphological analysis. STUDY DESIGN: Studies were carried out on Tianfu ducks on days 14, 18, 22, and 26 of embryogenesis (E14, E18, E22, and E26) as well as at 0 (neonatal stage), 1, 3, 5, 8, 11, 14, 17, 20, 26, 29, and 32 weeks of postnatal development (P0, P1, P3, P5, P8, P11, P14, P17, P20, P26, P29, and P32). RESULTS: NPY-like immunoreactivity (NPY-ir) was detected mainly in the epithelial reticular cells and vascular smooth muscles, slightly in the lymphocytes from E26 onwards. On E26, NPY-ir was restricted to the epithelial reticular cells of diffuse forms of Hassall's corpuscle (DHC). The integral optical density (IOD) values of NPY-ir cells in the cortex and medulla did not significantly change from P0 to P17, but then dramatically rose from P20 to P32. NPYY1-like immunoreactivity (NPYY1-ir) was observed mainly in the lymphocytes, slightly in the epithelial reticular cells of DHC and the vascular smooth muscles from E18 onwards. The IOD values of NPYY1-ir cells significantly increased from E18 to E22, then kept unchanged until P0, greatly increased on P3, and then remained stable until P17 but dramatically increased from P20 to P32. CONCLUSION: These results suggest that the possible interaction between NPY and NPYY1 may take place within the duck thymus chiefly during postembryonic development, which might be of great importance for the function of thymocytes, as well as duck thymus involution. PMID- 27386628 TI - Immunohistochemical Expression and Clinical Significance of Wnt11 and BCL2A1 in Complete Moles. AB - OBJECTIVE: To investigate Wnt11 and BCL2A1 immunohistochemical expression in complete moles and normal villi. STUDY DESIGN: The expression of Wnt11 and BCL2A1 in 84 complete moles and 30 normal first-trimester villi were detected by Envision immunohistochemistry. Quantitative evaluation according to color deconvolution and immunoreactive score was performed. Data was analyzed using Kruskal-Wallis test, Pearson test, and ROC curve. RESULTS: Of 84 complete moles, 14 developed to post-molar gestational trophoblastic neoplasia, and the others regressed spontaneously. Both proteins showed cytoplasmic pattern, whereas the DAB wt% of BCL2A1 and Wnt11 expression was highest in moles that developed to GTN, gradually reduced in spontaneously regressed moles and normal villi (all p < 0.01). We considered a 23.17% cutoff valuefor Wnt11 DAB wt% and 16.31% for BCL2A1 DAB wt% to assess molar progression to GTN. There was positive correlation between expressions of the 2 proteins (r = 0.403). CONCLUSION: Our findings demonstrated immunohistochemical expression of Wnt11 and BCL2A1 in complete moles and normal villi. Both proteins may be included as part of an immunohistochemical panel to identify postmolar outcome when other trophoblastic markers yield ambiguous results. PMID- 27386629 TI - Protective Effects of Vitamin E on Methotrexate-Induced Jejunal Mucosal Damage in Rats. AB - OBJECTIVE: To investigate the possible protective effects of Vitamin E (Vit E) on oxidative stress and jejunal damage in the rat intestinal mucosa after methotrexate (MTX)-induced enterotoxicity. STUDY DESIGN: Rats were divided into 3 groups: control, MTX, and MTX+ Vit E; each group contained 8 animals. The control group was given physiological serum in addition to sunflower oil for 3 days. The second group was given sunflower oil with intragastric tube daily, followed by MTX injection (20 mg/kg intraperitoneally). To the third group, starting 3 days before injection, Vit E was given dissolved in sunflower oil (600 mg/kg orally) in addition to MTX injection. Four days after MTX injection the anesthetized rats were sacrificed, and the tissue samples obtained from their jejunums were investigated for histological and biochemical analysis. RESULTS: Vit E treatment significantly decreased the elevated tissue malondialdehyde levels and increased the reduced glutathione peroxidase and superoxide dismutase activities in comparison to the MTX-treated group. MTX treatment caused severe histopathological injury including mucosal erosions, inflammatory cell infiltration, necrosis, hemorrhage, and villous congestion. Vit E treatment significantly attenuated the severity of intestinal injury caused by MTX via inhibiting induced nitric oxide synthase levels and NF-kappaB p65 activation. CONCLUSION: Because of its reconstructing and antioxidant effects, Vit E pretreatment may have protective effects in the intestinal tissue of MTX-treated rats. PMID- 27386631 TI - Effects of Cyclooxygenase on the Urothelium of the Urinary Bladder of Mice Exposed to Pelvic Radiation. AB - OBJECTIVE: To determine the role of cyclooxygenase (COX) expression in the urothelium of the urinary bladder during radiation injury caused by pelvic radiotherapy for cancer therapy. STUDY DESIGN: Twenty-four male Swiss Albino mice were separated into 4 groups. The first group was the control group (Group 1) and the second, third, and fourth groups were euthanized after 24 hours (Group 2), 48 hours (Group 3), and 7 days (Group 4), respectively. A single-fractioned 10 Gy of ionizing radiation was applied to all mice's pelvic zone with Co-60. Bladders were removed completely from the pelvic region. Histochemical analysis using hematoxylin and eosin and immunohistochemical analysis using anti-COX-1 and COX-2 antibodies were performed on tissue samples. The immunoreactivities of the urinary bladder were quantified using H-score measurement, and statistical comparison was performed. RESULTS: In the immunohistochemical examination the COX 1 immunoreactivities were found to be higher in the urothelium of the bladder in the radiation exposed groups than in the normal control group (group 1) (p < 0.005). Additionally, high immunoreactivity of COX-2 molecule was established in groups 2, 3, and 4 of radiation groups as compared to group 1 (p < 0.005) in examination of the urothelium. COX-1 and COX-2 immunoreactivities in the submucosa were detected higher in group 4 than in the other groups (p < 0.005). CONCLUSION: COX-1 and COX-2 expressions in the urothelium and subepithelium of the urinary bladder were investigated in mice during the acute radiation response. The expression of COX-1 and COX-2 in the urothelium seems to prevent bladder damage from radiation, supplying differentiation and restoration of the urothelium. PMID- 27386630 TI - Effects of Low-Intensity Treadmill Exercise on Sciatic Nerve in Experimental Diabetic Neuropathy. AB - OBJECTIVE: To investigate the potential beneficial effects of low-intensity exercise on histopathological changes of sciatic nerves in streptozotocin (STZ) induced diabetic rats. STUDY DESIGN: The rats were allotted randomly into 3 experimental groups: A (control), B (diabetic untreated), and C (diabetic treated with low-intensity exercise); each group contained 8 animals. Groups B and C received STZ. Diabetes was induced in 2 groups by a single intraperitoneal injection of STZ (40 mg/kg, freshly dissolved in 0.1 M citrate buffer, pH 4.2). Two days after STZ treatment, diabetes in 2 experimental groups was confirmed by measuring blood glucose levels. Rats with blood glucose levels >= 250 mg/dL were considered to be diabetic. Animals in the exercise group were made to run the treadmill once a day for 4 consecutive weeks. Exercise started 3 days prior to STZ administration. RESULTS: The treatment of low-intensity exercise caused a sharp decrease in the elevated serum glucose and an increase in the lowered serum insulin concentrations in STZ-induced diabetic rats. STZ induced a significant decrease in the area of insulin-immunoreactive beta cells. Low-intensity exercise treatment resulted in increased area of insulin-immunoreactive beta cells signficantly. Myelin breakdown decreased significantly after treatment with low intensity exercise. The ultrastructural features of degenerated axons also showed remarkable improvement. CONCLUSION: We believe that further preclinical research into low-intensity exercise may indicate its usefulness as a potential treatment for peripheral neuropathy in STZ-induced diabetic rats. PMID- 27386632 TI - Effects of Potentilla fulgens as a Prophylactic Agent in Tibial Defects in Rats. AB - OBJECTIVE: To investigate the effects of Potentilla fulgens as a prophylactic agent on tibial defects in the rat. STUDY DESIGN: Twenty-eight male Wistar albino rats weighing 200-215 g each were divided into 3 experimental groups. The tibial bone defect group served as the control group. The experimental groups were Potentilla fulgens with tibial defect (14 days) and Potentilla fulgens with tibial defect (28 days). Extract of Potentilla fulgens was mixed with water (400 mg/kg/day) and given to groups 14 and 28 as drinking water. The histopathological and immunohistochemical characteristics of each tibial bone cavity within each group were observed. The trabecular new bone formation was evaluated by expression rate of osteonectin and osteopontin. RESULTS: In the Potentilla fulgens + tibial defect group (14 days), trabecular bone had started combining extensive new bone formation, osteocyte cells were evident, and lamellar bone was formed. Osteoblasts showed a positive reaction with osteonectin. Osteopontin expression was positively observed between fibrous structures and in the osteoblast and osteocyte cells. This can be considered indicative of new bone formation. In the Potentilla fulgens + tibial defect group (28 days), an increase in expansion in trabecular bone and myeloid tissue was observed. Osteoblastic activity and osteocyte cells began to be observed in new bone fragments. CONCLUSION: In our study we show that Potentilla fulgens extract provided a protective effect on new bone formation and aided in the development of osteocytes and secretion of matrix in osteoblasts. Additionally, we show the inductive effect of the extract on new bone formation. In particular, the expression of osteopontin and osteonectin was also supported with the Western blot technique on the development of osteoblasts and osteocytes, showing a similar trend with our results. PMID- 27386633 TI - Effect of Zoledronic Acid Application on Different Graft Materials in Calvarial Bone Defect Models. An Experimental Analysis. AB - OBJECTIVE: To determine the effect of zoledronic acid on graft materials in bone calvarial defects. STUDY DESIGN: Eighty adult (12 weeks) Sprague-Dawley male rats weighing from 300-350 g were divided into groups: calvarial defect, calvarial defect + synthetic graft, and calvarial defect + xenograft. All groups received zoledronate intravenously for a week after surgery and were sacrificed at either 6 or 12 weeks after their operation. The rat calvariae were fixed in 10% neutral buffered formalin before decalcification in 10% ethylenediaminetetraacetic acid for 20 days. Calvarial bone samples were then dehydrated and processed for embedding in paraffin wax. Sections 5 MUm thick were stained with hematoxylin and eosin and examined by light microscopy. RESULTS: The effects of zoledronic acid, a third-generation nitrogen-containing bisphosphonate, on different graft materials in rats with critical-size calvarial defects were analyzed and compared. Significantly less graft resorption was identified in zoledronic acid treated rats that had received a xenograft than in either the untreated rats or those with a synthetic graft. In the xenograft group primary ossification was visible at week 12, and the graft had entered the bone to a greater extent than in the other experimental groups or in the control group. Osseous structures were also observed more clearly in this group than in the others. CONCLUSION: Zoledronic acid histopathologic bone graft stimulates bone formation. Zoledronic acid may be considered among the therapeutic methods available to improve the bone formation process in calvarial bone formation. PMID- 27386634 TI - Influence of Radiation Exposure During Radiotherapy. Evidence for the Increase of Versican and Heparin-Binding EGF-like Growth Factor Concentrations. AB - OBJECTIVE: To investigate the reaction of versican and heparin-binding EGF-like growth factor (HB-EGF) molecule concentrations to acute radiation exposure in normal bladder and rectal tissue samples in order to gain more insight into the effects of cancer radiotherapy. STUDY DESIGN: Four groups with 6 male adult Swiss Albino mice per group were investigated. The mice bladder and rectum tissue samples were subjected to a 10-Gy single-dose radiation exposure in the pelvic region with a Co-60 teletherapy device and investigated 1, 2, and 7 days after radiation exposure, with 1 reference group which was not exposed to radiation. RESULTS: In the immunohistochemical examination of the tissue samples with anti versican and anti-HB-EGF primary antibodies was observed a statistically significant increase 7 days after radiation exposure. CONCLUSION: The observed increase of versican and HB-EGF concentrations in the normal tissue matrix after radiation exposure may play a role in the side effects of radiotherapy. PMID- 27386635 TI - Malignant Bilateral Basifrontal Solitary Fibrous Tumor. A Case Report. AB - BACKGROUND: Solitary fibrous tumors are rare benign mesenchymal neoplasms characterized by involvement of many sites all over the body with uncommon presentation within the cranium. Furthermore, malignant bilateral basifrontal solitary fibrous tumor is extremely rare. Although uncommon, this rare entity may be included in the differential diagnosis of frontal tumors in adults, to ensure complete surgical resection. The tumor falls under the spectrum of fibroblastic proliferation and shares close morphological overlap with meningiomas and hemangiopericytomas, posing a diagnostic challenge for the histopathologist. CASE: We report a case of a malignant solitary fibrous tumor in the bilateral basifrontal region in a 50-year-old woman who presented with intermittent headache and vomiting and was clinicoradiologically diagnosed with meningioma. CONCLUSION: Clinicoradiological and pathological correlation is required for recognizing the aggressive behavior of this tumor and aiding the clinician for appropriate surgical management (complete surgical resection) and close sequential follow-up. PMID- 27386636 TI - Gentian Violet Used as an Epithelial Cell Monolayer Stain in the Scratch Wound Healing Assay. PMID- 27386637 TI - Report from Council on Advanced Practice. PMID- 27386638 TI - [Discussion on Clinical and Diagnosis Program of Integrative Medicine]. AB - Facing current situation of integrative medicine (IM), authors put forward that clinical and diagnosis program of IM could be carried out from clinical path, pathogenesis, treatment theory and philosophy, and so on, but with different integration degrees. Meanwhile, formulation of concrete program should be disease targetedly set up, and adjusted from person to person, from place to place, from time to time. As for settled IM program , authors could evaluate it from whether Chinese medicine and Western medicine have formed complementary, synergistic, excitatory actions, and toxicity attenuation; whether more problems could be solved in efficacy, safety, practicability, and economy than previous single mode. PMID- 27386640 TI - [Life in Attendance--Record of Prof. WANG Xue-mei, Peking University First Hospital]. PMID- 27386639 TI - [Perspective on the Development of Integrative Medicine Based on the Paradigm Theory: On the Connotation and Extension of Integrative Medicine]. AB - Integrative medicine (IM) has made great progress after more than half a century practice. However, many issues are yet to be in-depth explored. How to define clinical connotation and extension of IM, how to define feasible methods and means for diagnosis and treatment of IM, how to train more skilled talents of IM, how to elevate clinical efficacy of IM, these are all topics in need of further study. In this paper authors explored the clinical development mode of IM, extracted connotation and extension of IM clinics, hoping to promote the development of IM clinics. PMID- 27386641 TI - [Effect of Telbivudine Tablet Combined Jianpi Bushen Recipe on HBV Specific Cytotoxic T Lymphocyte and HBeAg Seroconversion in Patients with HBeAg Positive Chronic Hepatitis B]. AB - OBJECTIVE: To explore the effect of Telbivudine (LDT) Tablet combined with Jianpi Bushen Recipe (JBR) on serum hepatitis B virus (HBV) specific cytotoxic T lymphocyte (CTL) and HBeAg seroconversion in chronic hepatitis B (CHB) patients. METHODS: Totally 90 HBeAg-positive and human leukocyte antigen (HLA)-A2 positive CHB patients were randomly assigned to the treatment group and the control group, 45 cases in each group. Patients in the treatment group took LDT Tablet (600 mg, once per day) combined with JBR granule (twice per day), while those in the control group took LDT Tablet alone. The therapeutic course for all was one year. HBV DNA negative conversion rate, HBeAg seroconversion rate, and level of HBV specific CTL were compared after 1 year treatment; liver function, drug resistance mutations, and adverse reactions were also compared between the two groups. RESULTS: After 1 year treatment, HBV DNA negative conversion rate and HBeAg seroconversion rate were 88.89% (40/45) and 40.00% (18/45) in the treatment group, higher than those of the control group [68.89% (31/45) and 20.00% (9/45)], with statistical difference (P < 0.05). Level of HBV specific CTL in the treatment group was 0.78% +/- 0.09% after treatment, higher than that of the control group after 1 year treatment (0.54% +/- 0.11%) and that before treatment (0.36% +/- 0.07%), with statistical difference (P < 0.01). Level of HBV specific CTL in 27 patients with HBeAg seroconversion was 0.81% 0.10%, higher than that of 63 patients without HBeAg seroconversion (0.60% +/- 0.09%), with statistical difference (P < 0.01). ALT returned to normal in 44 cases of the treatment group (97.78%), while it was 42 cases (93.33%) of the control group, with no statistical difference between the two groups (P > 0.05). Total bilirubin (TBil) in the two groups all turned to normal. rtM204I variation occurred in 1 case (2.22%) of the treatment group and 2 cases (4.44%) in the control group. No obvious adverse reaction occurred in the two groups. CONCLUSION: LDT Tablet combined with JBR could elevate levels of HBV specific CTL and HBeAg seroconversion in CHB patients. PMID- 27386642 TI - [Efficacy Observation of Yiguanjian Decoction Combined Adefovir Dipivoxil Tablet in Treating HBeAg Negative Chronic Viral Hepatitis B Active Compensated Liver Cirrhosis Patients]. AB - OBJECTIVE: To explore clinical efficacy of Yiguanjian Decoction (YD) combined Adefovir Dipivoxil Tablet (ADT) in treating HBeAg negative chronic viral hepatitis B (CVHB) active compensated liver cirrhosis (LC) patients. METHODS: Totally 68 HBeAg negative CVHB active compensated LC patients initially treated were assigned to the treatment group and the control group using random digit table, 34 in each group. Patients in the control group took ADT alone, 10 mg each time, once per day. Those in the treatment group additionally took YD, one dose per day. The therapeutic course for all was 48 weeks. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) were detected once in every two weeks. Hepatitis B virus (HBV)-DNA and four items of serum liver fibrosis [procollagen type I (PCN), hyaluronidase (HA), procollagen III peptide (PCIII), laminin (LN)] were detected once per every 4 weeks. Abdominal ultrasound B was performed before and after treatment. The inner diameter of the portal vein and the size of spleen were recorded. The fibrosis degree of liver was evaluated using Fibroscan. Efficacy of Chinese medicine (CM) was evaluated between the two groups before and after treatment using CM syndrome integrals. Efficacy of Western medicine (WM) was also evaluated between the two groups using Child-Pugh grading. Results Compared with before treatment in the same group, ALT and AST levels restored to normal levels, HBV-DNA turned negative (HBV-DNA < or = 1 x 10(2)) in the two groups after 48-week treatment. Besides, levels of TBil, ALB, PCIV, HA, PCIII, and LN obviously decreased (P < 0.05, P < 0.01). Results of ultrasound B showed the inner diameter of the portal vein and the size of spleen decreased. Fibroscan results showed that the elasticity value of the liver obviously decreased (P < 0.05). Besides, post-treatment levels of PCIV, HA, PCEJ, and LN, and the elasticity value of the liver decreased more obviously in the treatment group than in the control group (P < 0.01). There was no statistical difference in post-treatment levels of ALT, AST, TBil, ALB, inner diameter of the portal vein, or the size of spleen between the two groups (P > 0.05). Compared with before treatment in the same group, scores of Chinese medical syndrome and Child-Pugh scores decreased in the two groups after treatment (P < 0.05, P < 0.01). Besides, scores of Chinese medical syndrome decreased more obviously in the treatment group than in the control group (P < 0.05). The effective rate was 8824% (30/34) in the treatment group, higher than that of the control group [67.65% (23/34)] with statistical difference (P <0.05). Conclusion Combined treatment of YD and ADT could significantly improve symptoms of CM and fibrosis degree of liver of HBeAg negative CVHB active compensated LC patients. PMID- 27386643 TI - [Correlation between Constitution of Yin Deficiency Syndrome and Polymorphism of HLA-DQA1/Treatment Response of Peg-IFNalpha Therapy in HBeAg Positive Chronic Hepatitis B Patients]. AB - OBJECTIVE: To observe the correlation between constitution of yin deficiency syndrome (YDS) and polymorphism of HLA-DQA1/treatment response of Peg-lFNalpha therapy in HBeAg positive chronic hepatitis B (CHB) patients, and to explore constitution of Chinese medicine (CM) in response of interferon therapy. METHODS: Totally 120 HBeAg positive CHB patients who were treated with Peg-IFNalpha were enrolled, and assigned to YDS group (59 cases) and non-YDS group (61 cases) according to classification of CM constitutions. All patients were subcutaneously injected with Peg-IFNalpha-2b (1.0 microg/kg body weight) or Peg-IFNalpha-2a (180 microg), once per week. Effective efficacy was primarily judged when complete response (CR) or partial response (PR) was obtained at month 6. Those with CR or PR completed 1 year therapeutic course. HLA-DQA1 gene types were detected by polymerase chain reaction sequence specific primers (PCR-SSP). The distribution difference of CM constitutions in patients with CR or PR and their inter-group HLA-DQA1 allele frequency were compared. RESULTS: Different treatment responses of Peg-IFNalpha were observed in CHB patients of two different CM constitutions. The ratio of CR + PR was 61.0% (36/59) in YDS group, obviously lower than that in NYDS group [78.7% (48/61), P < 0. 05]. Patients with CR had a lower allele frequency of HLA-DQA1 * 0501 than those with no-response [14.8% (8/54) vs. 30.6% (22/72)] with statistical difference (P < 0.05). Patients with CR had a higher allele frequency of HLA-DQA1 * 0601 than those with no-response [18.5% (10/54) vs. 5.6% (4/72)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0301 was lower in YDS group than in non-YDS group [2. 5% (3/118) vs. 9.8% (12/122)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0501 was higher in YDS group than in non-YDS group [33.9% (40/118) vs. 18.9% (23/122)] with statistical difference (P < 0.05). Yet statistical significance was lost after adjustment (Pc > 0.05 for both). CONCLUSIONS: Both constitutions of CM and HLA-DQA1 gene polymorphism af- fect HBeAg positive CHB patients' response to Peg-INFalpha. Constitutions of YDS and HLA-DQA1 * 0501 was not favorable to response, their association needed to be further studied. PMID- 27386644 TI - [Efficacy of Zaozhu Yinchen Recipe for Treating Non-alcoholic Steatohepatitis and its Effect on Free Fatty Acid and TNF-alpha]. AB - OBJECTIVE: To observe the efficacy of Zaozhu Yinchen Recipe (ZZYCR) on non alcoholic steatohepatitis (NASH) patients, and to explore its effect on serum free fatty acid (FFA) and tumor necrosis factor alpha (TNF-alpha). METHODS: Totally 120 patients with NASH were randomly assigned to the treatment group (60 cases, treated with ZZYCR, one dose per day) and the control group (60 cases, treated with Silibin Meglumine Tablets, 20 mg each time, thrice per day). The therapeutic course for all was 24 weeks. Serum levels of ALT and AST activities, TC and TG levels were detected before and after treatment. Peritoneal CT was performed in all patients, and CT ratios of liver and spleen calculated. NAFLD activity score (NAS) and degree of hepatic fibrosis were assessed using pathological examinations of liver tissue, and efficacy also evaluated. Serum contents of FFA and TNF-alpha were also detected. RESULTS: Compared with before treatment in the same group, activities of ALT and AST, serum levels of TC, TG, FFA, and TNF-alpha, NAS, scores of symptoms and signs all obviously decreased, degree of hepatic fibrosis was obviously improved in the two groups (P < 0.05, P < 0.01). These changes were more obviously seen in the treatment group (P < 0.05). After 24-week treatment, the total effective rate and total clinical efficacy were 80.00% (48/60 cases) and 85.00% (51/60 cases) in the treatment group, obviously higher than those in the control group [60.00% (36/60 cases) and 73.33% (44/60 cases) respectively], with significant difference (P < 0.05, P < 0.01). CONCLUSION: ZZYCR could improve the clinical efficacy of NASH patients, and its mechanism might be associated with inhibiting serum levels of FFA and TNF alpha. PMID- 27386645 TI - [Analysis of Compatibility Laws for Acupoint Selection of Acupuncture in Treating Diabetic Gastroparasis]. AB - OBJECTIVE: To summarize and analyze the compatibility laws for acupoint selection of acupuncture in treating diabetic gastroparasis (DGP) in modern literatures of clinical researches. METHODS: Retrieved were literatures related to treating DGP by acupuncture or acupuncture combined other therapies from PubMed, CNKI, and WF from 1982 to 2014. Analyzed were frequency of acupoint use, meridians selected acupoints belonged to, regions selected, association laws of selected compatible acupoints. RESULTS: Retrieved were 35 with compatibility frequencies more than 15 listed as follows: compatibility frequency of Zusanli (ST36) and Zhongwan (CV12) was 33 (94.29%); compatibility frequency of Zusanli (ST36) and Neiguan (PC6) was 23 (65.71%), compatibility frequency of Zhongwan (CV12) and Neiguan (PC6) was 22 (62.86%), compatibility frequency of Zusanli (ST36), Zhongwan (CV12), and Neiguan (PC6) was 22 (62.86%); compatibility frequency of Zusanli (ST36) and Sanyinjiao (SP6) was 16 (45.71%); compatibility frequency of Zhongwan (CV12) and Sanyinjiao (SP6) was 16 (45.71%); compatibility frequency of Zusanli (ST36), Zhongwan (CV12), and Sanyinjiao (SP6) was 15 (42.86%). Meridians selected acupoints belonged to were sequenced as Foot Yangming Stomach channel, Ren channel, Foot Taiyang Bladder channel, and so on. Acupoints selected were mainly in lower limbs, chest and abdomen, waist and back. The compatibility of Zusanli (ST36) and Zhongwan (CV12) was the most often used with the highest frequency. CONCLUSIONS: The compatibility laws for acupoint selection of acupuncture in treating DGP were mainly dominated as upper-lower selection, three regions selection, local selection, anterior-posterior selection. The compatibility laws for acupoint selection of acupuncture along meridians were mainly dominated as the convergence points and exterior-interior meridian points. PMID- 27386646 TI - [Amplitude Changes of Low Frequency Fluctuation in Brain Spontaneous Nervous Activities Induced by Needling at Hand Taiyin Lung Channel]. AB - OBJECTIVE: To observe amplitude changes of low frequency fluctuation in brain spontaneous nervous activities induced by needling at Hand Taiyin Lung Channel, and to preliminarily explore the possible brain function network of Hand Taiyin Lung Channel. METHODS: By using functional magnetic resonance imaging (fMRI), 16 healthy volunteers underwent resting-state scanning (R1) and scanning with retained acupuncture at Hand Taiyin Lung Channel (acupuncture, AP). Data of fMRI collected were statistically calculated using amplitude of low frequency fluctuations (ALFF). RESULTS: Under R1 significantly enhanced ALFF occurred in right precuneus, left inferior parietal lobule, bilateral superior temporal gyrus, bilateral middle frontal gyrus, left superior frontal gyrus, left inferior frontal gyrus, left medial frontal gyrus. Under AP significantly enhanced ALFF occurred in right precuneus, bilateral superior frontal gyrus, cerebellum, bilateral middle frontal gyrus, right medial frontal gyrus, and so on. Compared with R1, needing at Hand Taiyin Lung Channel could significantly enhance ALFF in right gyrus subcallosum and right inferior frontal gyrus. Significant decreased ALFF appeared in right postcentral gyrus, left precuneus, left superior temporal gyrus, left middle temporal gyrus, and so on. CONCLUSION: Needing at Hand Taiyin Lung Channel could significantly change fixed activities of cerebral cortex, especially in right subcallosal gyrus, right inferior frontal gyrus, and so on. PMID- 27386647 TI - [Effect of Tanshinone IIA in Preventing and Treating Oxaliplatin Induced Peripheral Neuropathy]. AB - OBJECTIVE: To observe preventive and therapeutic effects of Tanshinone IIA (T II A) on oxaliplatin induced peripheral neuropathy (OlPN) and to explore its effects on the expression of calcitonin gene related peptide (CGRP) and never growth factor (NGF). METHODS: Totally 36 phase II - III patients with malignant tumor of digestive tract undergoing chemotherapy program with oxaliplatin, were equally assigned to the T II A group (using THA at 80 mg/day 1 day before oxaliplatin chemotherapy for 3 successive days) and the control group (using chemotherapy program with oxaliplatin alone) by segmented randomization. After 4 cycles of chemotherapy, the incidence degree and incidence of OlPN were evaluated. Sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity ( MNCV) were tested by EMG evoked potential device. Serum levels of CGRP and NGF were also detected in the two groups before and after chemotherapy. The correlation of serum levels of CGRP and NGF to OIPN was assessed using linear correlation analysis. RESULTS: After chemotherapy the OlPN incidence was 27.8% (5/18 cases) in the T II A group, obviously lower than that in the control group (55.6%, 10/18 cases; P < 0.05). Compared with before treatment in the same group, SNCV and MNCV of common peroneal nerve were slowed down, serum NGF levels decreased, and serum CGRP levels obviously increased in the two groups (all P < 0.05). Compared with the control group after treatment, SNCV and MNCV of common peroneal nerve were obviously accelerated, serum NGF levels increased, and serum CGRP levels obviously decreased in the THA group (all P < 0.05). Results of linear correlation analysis indicated serum NGF level was negatively correlated with peripheral neuropathy (PN), serum CGRP expression was positively correlated with neurotoxicity (P < 0.05). CONCLUSION: T II A could reduce the incidence of OlPN, which might be associated with inhibiting the expression of CGRP and up regulating NGF activities. PMID- 27386648 TI - [Relationship between Life Habits and Constitution Types of Chinese Medicine in the Senile Living at Home in Beijing Downtown]. AB - OBJECTIVE: To investigate the distribution of constitution types of Chinese medicine (CM) in the elderly living at home in Beijing downtown, and to explore its relationship with life habits. METHODS: A total of 3894 senile more than 60 years old were enrolled in this study. Their constitution types of CM were typed using CM constitution questionnaire. Meanwhile, their demographic features, disease condition, diet habits, exercise habits, sleep habits, and so on were investigated. Multivariate Logistic regression analysis was used to evaluate the relationship between life habits and constitution types of CM. RESULTS: The number of mild type constitution senile was 1111 (28.53%) and the number of biased constitutions 2783 (71.47%). Biased constitutions of the top three were qi deficiency constitution (662, 17.00%), yang deficiency constitution (445, 11.43%), and blood stasis constitution (363, 9.32%). Univariate analysis showed that different habits of diet, exercise, and sleep exist among the senile of different constitutions (P < 0.05). By taking mild type constitution, multivariate Logistic regression analysis (except demographic indices and chronic history) showed that significantly positive correlation existed between qi deficiency constitution and favor for hot food (OR = 1.349, P = 0.015), yang deficiency constitution and favor for hot food (OR = 2.448, P < 0.01), phlegm wetness constitution and favor for barbecue food (OR = 2.144, P = 0.003), wet heat constitution and favor for sweet food (OR = 1.355, P = 0.032), wet-heat constitution and favor for tea (OR = 1.359, P = 0.047), blood stasis constitution and favor for hot food (OR = 1.422, P = 0.017), and qi depression constitution and favor for hot food (OR = 1.446, P = 0.031). Regular exercise had negative correlation with qi deficiency constitution (OR = 0.397, P < 0.01), yang deficiency constitution (OR = 0.522, P < 0.01) , phlegm-wetness constitution (OR = 0.475, P < 0.01), wet-heat constitution (OR = 0.647, P = 0.015), blood stasis constitution (OR = 0.608, P = 0.001), qi depression constitution (OR = 0.541, P = 0.001), and special diathesis constitution (OR = 0.466, P < 0.01). Early sleep and rise habit had negative with phlegm-wetness constitution (OR = 0.414, P < 0.01), wet-heat constitution (OR = 0.536, P = 0.015), blood stasis constitution (OR = 0.515, P = 0.004), and special diathesis constitution (OR = 0.526, P = 0.039). CONCLUSIONS: Different constitution types of CM might be highly related to specific life habits. Cultivating better life habits can improve biased constitutions of CM. PMID- 27386649 TI - [Correlation between Signs of Living Body in Abdominal and Pelvic Cavities and Syndrome Typing of Chinese Medicine in Colorectal Cancer Patients]. AB - OBJECTIVE: To explore the correlation between signs of living body in abdominal and pelvic cavities and syndrome typing of Chinese medicine (CM) in colorectal cancer patients. METHODS: Totally 112 colorectal cancer patients undergoing open abdominal surgery or laporoscopic surgery were syndrome typed as five types, i.e., inner-accumulation of damp and heat, blockage of stasis and toxin, Pi-Shen yang deficiency, blood-qi deficiency, Gan-Shen yin deficiency. Signs of living body in abdominal and pelvic cavities were collected. The correlation between signs of living body in abdominal and pelvic cavities and syndrome typing of CM were analyzed. RESULTS: Red colorectal canals or mass were dominated in colorectal cancer patients with inner-accumulation of damp and heat syndrome. Dark purple colorectal canals or mass were dominated in colorectal cancer patients with blockage of stasis and toxin syndrome. Reddish colorectal canals or mass were dominated in colorectal cancer patients with blood-qi deficiency syndrome. Pale colorectal canals or mass were dominated in colorectal cancer patients with Pi-Shen yang deficiency syndrome. Whitish or red-white stripes were dominated in colorectal cancer patients with Gan-Shen yin deficiency syndrome. Dropsy colorectal canal was associated with Pi-Shen yang deficiency syndrome. Intracavitary effusion was often seen in colorectal cancer patients with inner accumulation of damp and heat syndrome. The effusion was yellowish in less amount. Intracavitary adhesion was often seen in colorectal cancer patients with blockage of stasis and toxin syndrome. There was no correlation between the maximum diameter of mass or each syndrome type of CM. CONCLUSION: There existed correlation between signs of living body in abdominal and pelvic cavities and syndrome typing of CM, which could be taken as one of references for syndrome typing of colorectal cancer patients. PMID- 27386650 TI - [Effect of Osthole on Adrenocortical Function in Y1 Mouse Adrenocortical Tumor Cells]. AB - OBJECTIVE: To study the effect of osthole (Ost) on adrenocortical function in Y1 mouse adrenocortical tumor cells. METHODS: Y1 mouse adrenocortical tumor cells were taken as subjects in this experiment. In 10.0%, 1.0%, and 0.1% serum DMEM F12 medium, Y1 cells were treated with 1, 10, 25, 50, 100, and 200 micromol/L Ost for 24 and 48 h. 0.1% Dimethyl Sulfoxide (DMSO) was taken as negative control group and 1 mmol/L (Bu) 2cAMP as positive control group. Cell growth morphology was observed under inverted microscope. Contents of corticosterone were tested by ELISA. Expression levels of steroids synthase such as Star, Cyp11a1, Cyp21a1, Hsd3b2, Cyp11b1, Cyp11b2, Cyp17a1, and Hsd17b3 mRNA were detected by Real time quantitative PCR (RT-qPCR). RESULTS: Y1 cell proliferation was obviously inhibited by 100 and 200 micromol/L Ost, and its inhibitory effect was more significant in 0.1% serum medium. Compared with the negative control group, gene expressions of Star, Cyp11a1 , Cyp21a1, Hsd3b2, Cyp11b1, Cyp17a1, and Hsd17b3 were significantly enhanced in the posi- tive control group (P < 0.05). Y1 cell corticosterone levels significantly increased in 50 micromol/L Ost treatment group after 24-and 48-h intervention (P < 0.05). Contents of corticosterone increased more obviously in 25 and 50 +/- mol/L Ost treatment groups after 48-h intervention, as compared with 24-h intervention (P < 0.01). After 24-h intervention, expression levels of Star, Cyp21a1, and Hsd3b2 genes were significantly up-regulated in 25 and 50 lLmol/L Ost groups (P < 0.05). Star gene expression was further enhanced after 48-h intervention (P < 0.05). However, Ost showed no effect on Cyp11a1 (P > 0.05). Additionally, gene expressions of Cyp11b1 and Cyp17a1 were significantly enhanced by 10, 25, and 50 pLmolIL Ost after treatment for 24 and 48 h (P < 0.05). Ost showed no obvious effect on Cyp11b2 and Hsd17b3 expressions. CONCLUSION: Ost could regulate adrenal cortex function and promote corticosterone synthesis and secretion through strengthening gene expressions of steroidogenic enzymes. PMID- 27386651 TI - [Effect of Pinggan Qianyang Recipe Containing Serum on Angiotensin II Induced Vascular Smooth Muscle Cell Proliferation and Migration and DNA Methylation]. AB - OBJECTIVE: To observe the effect of Pinggan Qianyang Recipe (PQR) on inhibiting angiotensin II (Ang II) induced proliferation and migration of vascular smooth muscle cells (VSMCs) and changes of DNA methylation. METHODS: VSMCs were cultured using tissue explant method, and PQR containing serum was prepared. Primarily cultured VSMCs were divided into four groups, the normal group, the model group, the folate group (folic acid intervention) , and the PQR group. The proliferation and migration of VSMCs was duplicated by Ang II. After 24-h Ang II induced culture, 40 microg/mL folic acid was added to the folate group for 48 h, while 5% PQR containing serum was added to the PQR group for 48 h. The cell growth curve of VSMCs was drawn by using Cell Counting Kit (CCK-8). The proliferative activity of VSMC was determined by MTT assay. The migration of VSMCs was measured by Millicell chamber. The general level of cytosine methylation in cell nucleus was detected via 5-mC antibodies immunofluorescence, and mRNA expression levels of DNA methyltransferase 1 (DNMT1) were measured by Real-time q-polymerase chain reaction (q-PCR). RESULTS: VSMCs were promoted by Ang II at 10(-6) mol/L for 24 h. Compared with the normal group, the proliferative activity and migration quantity of VSMCs obviously increased, and DNA methylation level obviously decreased (P < 0.05, P < 0.01). Compared with the model group, the cell growth, proliferative activity and migration quantity of VSMCs obviously decreased and the general DNA methylation level increased in the folate group and the PQR group (P < 0.05, P < 0.01). Compared with the normal group, the mRNA expression of DNMT1 decreased in the model group (P < 0.01). Compared with the model group, mRNA expression of DNMT1 in Ang II induced VSMCs was obviously enhanced in the folate group and the PQR group (P < 0.01). CONCLUSIONS: PQR could inhibit Ang II induced proliferation and migration of VSMCs, and cause high genomic DNA methylation level. Changes of DNA methylation might be associated with DNMT1 expression. PMID- 27386652 TI - [Effects of Shoutai Pill Containing Serum on Bioactivity Behavior of Trophoblast Cells of Spontaneous Abortion Patients]. AB - OBJECTIVE: To explore the effect of Shoutai Pill (STP) containing serum on bioactivity behaviors of trophoblast cells in spontaneous abortion (SA) patients such as cell proliferation, invasion, migration and secretion. METHODS: Trophoblast cells in artificial abortion in normal pregnancy and SA patients were isolated and cultured in vitro, which were then treated with STP containing serum at various concentrations (5%, 10%, 20%, respectively). Blank serum was taken as the normal control group and dydrogesterone containing serum as the dydrogesterone control group. The proliferation, cycle distribution, invasion and migration capacity, and beta human chorionic gonadotropin (p-HCG) level were detected by methyl thiazolyl tetrazolium (MTT) colorimetry, flow cytometry (FCM), Transwell experiments, and ELISA, respectively. RESULTS: Compared with the normal control group, the activity of cell proliferation obviously decreased, ratios of apoptotic cells (SubGO/G1) and G2/M phase were obviously elevated, S phase cell ratio was obviously reduced (all P < 0.05). Transwell experiments indicated invasion and migration capacity obviously decreased, secreted beta-HCG level were obviously reduced after 72-h intervention (P < 0.05). Compared with the SA group, the activity of cell proliferation obviously increased, ratios of apoptotic cells and G2/M phase were obviously reduced, S phase cell ratio was obviously elevated, invasion and migration capacity were obviously enhanced, secreted beta-HCG level were obviously elevated after 72-h intervention in the dydrogesterone control group and each STP containing serum group (all P < 0.05). The activity of trophoblastic cell proliferation, S phase cell ratio, invasion and migration capacity, and secreted beta-HCG level were strengthened along with increased STP containing serum. Besides, the effects of 20% STP containing serum group were significantly superior to those of the dydrogesterone control group (P < 0.05). CONCLUSION: STP containing serum could dose-dependently enhance the proliferative activity of trophoblastic cells, invasion and migration capacity, secretion of beta-HCG, and reduce the apoptosis of trophoblast cells, which might be one of mechanisms for STP preventing and treating SA. PMID- 27386653 TI - [Effect of Modified Hangqi Chifeng Decoction Containing Serum on the Expression of Col IV, MMP-2, and TIMP-2 in Glomerular Mesangial Cells Induced by LPS]. AB - OBJECTIVE: To explore the effect of Modified Hangqi Chifeng Decoction (MHCD) on levels of collagen type IV (Col IV), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2) in extracellular matrix (ECM) of glomerular mesangial cells (GMCs) in LPS induced mice. METHODS: Normal serum and telmisartan, high, medium, low dose MHCD containing serums were prepared by using serum pharmacology method. GMCs were cultured in vitro. The proliferation of mesangial cells were induced using LPS as stimulating factor. GMCs were divided into six groups, i.e., the normal group, the model group, the telmisartan group, high, medium and low dose MHCD groups. Col IV content in the supernatant of mesangial cells was detected using ELISA. Protein expressions of MMP-2 and TIMP-2 were detected using Western blot. RESULTS: Compared with the normal group, Col IV content obviously increased in the model group after 72-h LPS stimulation; protein expressions of MMP-2 and TIMP-2 were obviously up-regulated, and MMP 2/TIMP-2 ratio was down-regulated in the model group (P < 0.01). Compared with the model group, Col IV content obviously decreased in high and medium dose MHCD groups and the telmisartan group (P < 0.01); protein expressions of MMP-2 were obviously down-regulated in medium and low dose MHCD groups (P < 0.01, P < 0.05); the protein expression of TIMP-2 was obviously down-regulated in high, medium, low dose MHCD groups and the telmisartan group (P < 0.01). The pro- tein expression of TIMP-2 was obviously lower in the high dose MHCD group than in the low dose MHCD group (P < 0.01). MMP-2/TIMP-2 ratio was obviously up-regulated in the telmisartan group, high and medium dose MHCD groups (P < 0.01). CONCLUSION: MHCD could regulate disordered MMP-2/TIMP-2 ratio in LPS induced ECM, inhibit excessive production of Col IV in ECM, promote the degradation of ECM, reduce the accumulation of ECM, thereby, delaying the process of glomerular sclerosis. PMID- 27386654 TI - [Learning and Memory Capacity and NMDA Receptor Expression in Shen Deficiency Constitution Rats]. AB - OBJECTIVE: To explore material bases and neurobiological mechanisms of "Shen storing will" by observing learning and memory capacities and N-methyl-D-aspartic acid (NMDA) receptor expressions in Shen deficiency constitution (SDC) rats. METHODS: Totally 40 SD rats were randomly divided into the model group, the Zuogui Pill (ZP) group, the Yougui Pill (YP) group, the blank control group (consisting of normal pregnant rats), 10 in each group. SDC young rat model (inherent deficiency and postnatal malnutrition) was prepared by the classic way of "cat scaring rat". Medication started when they were scared by cat. Rats in the ZP group and the YP group were administered by gastrogavage with ZP suspension 0.1875 g/mL and YP suspension 0.0938 g/mL respectively. Equal volume of normal saline was administered to rats in the blank control group and the model group by gastrogavage. All medication was given once per day, 5 days in a week for 2 consecutive months. Learning and memory capacities were detected by Morris water maze test. Expressions of NMDA receptor subunits NR2A and NR2B in hippocamus were detected by immunohistochemical method. RESULTS: Compared with the blank control group, the latency period, total distance in Morris water maze test were longer in the model group (P < 0.05). All the aforesaid indices all decreased in the ZP group and the YP group, with statistical difference when compared with the model group (P < 0.05). The protein expressions of NR2A and NR2B in hippocamus were lower in the model group than in the blank control group (P < 0.05). But when compared with the model group, they were obviously higher in the ZP group and the YP group (P < 0.05). CONCLUSIONS: SDC rats had degenerated learning and memory capacities and lowered NMDA receptor expressions. ZP and YP could up-regulate learning and memory capacities and NMDA receptor expressions, thereby improving deterioration of brain functions in SDC rats. PMID- 27386655 TI - [Effect of Wenyang Huoxue Lishul Recipe Containing Serum on Expression of Cathepsin L in Puromycin Aminonucleoside-induced Injury of Mouse Glomerular Podocytes]. AB - OBJECTIVE: To observe the effect of Wenyang Huoxue Lishui Recipe (WHLR) containing serum on the expression of cathepsin L (CatL) in puromycin aminonucleoside-induced injury of mouse glomerular podocytes. METHODS: Mouse podocyte cells (MPCs) in vitro cultured were divided into the normal control group, the model group, the dexamethasone (DEX) group, 10% WHLR containing serum group, 20% WHLR containing serum group, the vehicle serum control group. MPCs in the normal control group were cultured at 37 degrees C culture solution for 24 h. 45 mg/L puromycin was acted on MPCs in the model group for 24 h. On the basis of puromycin intervention, 1 limol/L DEX was co-incubated in MPCs of the DEX group for 24 h; 10% or 20% WHLR containing serum was co-incubated in MPCs of the 10% WHLR containing serum group and 20% WHLR containing serum group for 24 h. The vehicle serum control group was also set up by incubating with WHLR containing serum alone for 24 h. The expression of CatL and its substrate Synaptopodin in podocytes were detected by cell immunofluorescence staining. FITC-conjugated phalloidin was used to stain F-actin. A cortical F-actin score index (CFS index) was designed to quantify the degree of cytoskeletal reorganization in cultured podocytes. RESULTS: Compared with the normal control group, the expression of synaptopodin significantly decreased and the expression of CatL significantly increased in the model group. F-actin arranged in disorder, gradually forming pericellular F-actin ring. CFS index was obviously elevated (P < 0.01). Compared with the model group, the epression of synaptopodin increased, the expression of CatL decreased, and CFS index also decreased in the DEX group, 10% WHLR containing serum group, and 20% WHLR containing serum group (P < 0.05, P < 0.01). Compared with the DEX group, the expression of synaptopodin decreased in 10% WHLR containing serum group, CFS index also decreased in 20% WHLR containing serum group (P < 0.05). CONCLUSIONS: WHLR could up-regulate the expression of synaptopodin, down-regulate the expression of CatL, and alleviate cytoskeletal reorganization of F-actin. It was helpful to stabilize the cytoskeleton of F actin and improve the merging of podocytes. PMID- 27386656 TI - [Preventive Effect of Different Compatibilities of Ramulus Cinnamomi and Radix Paeomlae alba in Guizhi Decoction on Cardiac Sympathetic Denervation Induced by 6 OHDA]. AB - OBJECTIVE: To observe the preventive effect of different compatibilities of Ramulus Cinnamomi (RC) and Radix Paeomiae alba (RPA) in Guizhi Decoction (GZD) on neurotransmitters and their rate-limiting enzymes, and neurotrophic factors of cardiac sympathetic denervation model rats induced by 6-hydroxydopamine (6-OHDA). METHODS: Totally 54 male Wistar rats were randomly divided into 6 groups, i.e., the blank control group, the model group, the methycobal group, the 2:1 (RC/RPA) Guishao group, the 1:2 Guishao group, and the 1:1 Guishao group, 9 in each group. Sympathetic denervation was induced by intraperitoneal injection of 6-OHDA for three successive days. Rats in the methycobal group and GZD groups were administered with corresponding decoction by gastrogavage 1 week before modeling (methycobal at the daily dose 0.15 mg/kg; GZD at the daily dose of 4.0, 5.5, 5.5 g crude drugs/kg for GZD 1:1, 1:2, and 2:1 groups). All medication lasted for 10 successive days. Levels of norepinephrine (NE), tyrosine hydroxylase (TH), choline acetyl-transferase (ChAT), nerve growth factor (NGF), growth associated protein43 (GAP-43) and ciliary neurotrophic factor (CNTF) in myocar- dial homogenates of right atrium and ventricular septum were detected by ELISA. RESULTS: Compared with the blank control group, levels of NE, TH, TH/ChAT ratio, and GAP-43 in myocardial homogenates of right atrium and ventricular septum decreased in the model group, and level of NGF increased (P < 0.01, P < 0.05). Compared with the model group, levels of NE and GAP-43 increased in the right atrium and interventricular septum; NGF level of the ventricular septum decreased in the methycobal group and each GZD groups. TH and TH/ChAT ratio in the right atrium increased in the 2:1 Guishao group and the 1:2 Guishao group (P < 0.01, P < 0.05); NGF levels in the right atrium and interventricular septum decreased only in the 1:1 Guishao group (P < 0.01, P< 0.05). Compared with the methycobal group, levels of NE, TH, and GAP-43 in the right atrium and interventricular septum increased, and NGF levels in the right atrium and interventricular septum decreased in the 1:1 Guishao group (P < 0.05). Compared with the methycobal group, levels of NE and GAP-43 in interventricular septum increased in the 2:1 Guishao group (P < 0.05). CONCLUSION: GZD (with the proportion between RC and RPA 2:1 and 1:1) could improve contents of neurotransmitters and their rate-limiting enzymes, as well as neurotrophic factors in cardiac sympathetic denervation model rats induced by 6-OHDA, alleviate cardiac sympathetic denervation induced by 6 OHDA, and maintain the balance of sympathetic-vagal nerve system. PMID- 27386657 TI - [Effect of Total Ravonoids of Herba Epimedium on BMP-2/RunX2/OSX Signaling Pathway during Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells]. AB - OBJECTIVE: To explore the effect of total flavonoids of Herba Epimedium (FHE) on BMP-2/RunX2/OSX signaling pathway in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). METHODS: Passage 3 BMSCs were randomly divided into the control group, the experimental group, and the inhibitor group. BMSCs in the control group were cultured in 0.2% dimethyl sulfoxide + Osteogenuxic Supplement (OS) fluid + DMEM/F12 culture media. BMSCs in the experimental group were intervened by 20 microg/mL FHE. BMSCs in the inhibitor group were intervened by 20 microg/mL FHE and 1 microg/mL NOGGIN recombinant protein. At day 9 alkaline phosphatase (ALP) activity was measured. Calcium nodules were stained by alizarin red staining and the density was observed. The transcription expression of osteogenic differentiation-related proteins (type I collagen, osteocalcin, and osteopontin) and related factors of BMP-2/RunX2/OSX signaling pathway was assayed by RT-PCR. RESULTS: Compared with the control group, ALP activities were enhanced and the density of calcium nodules significantly increased; type I collagen, osteocalcin, and osteopontin expression levels were increased in the experimental group. The expression of osteogenesis related transcription factor was also increased in the experimental group. Noggin recombinant protein inhibited FHE promoting BMSCs osteogenesis in the inhibitor group. Compared with the experimental group, ALP activity decreased (P < 0.05), the density of calcium nodules was lowered, expression levels of type I collagen, osteocalcin, osteopontin significantly decreased (P < 0.05) in the inhibitor group. CONCLUSION: 20 microg/mL FHE promoted osteogenic differentiation process of BMSCs by BMP-2/RunX2/OSX signaling pathway. PMID- 27386658 TI - [Effect of Yangxue Qingnao Granule on the Expression of CD11b in CA1 Region of Hippocampus of Vascular Dementia Rats]. AB - OBJECTIVE: To observe the effect of Yangxue Qingnao Granule (YQG) on the expression of CD11b in CA1 region of hippocampus of vascular dementia rats, and to explore its regulation on microglias. METHODS: Totally 144 SD rats were randomly divided into the sham-operation group, the vascular dementia model group (model), and the YQG treated group (treated). The vascular dementia rat model was prepared by modified Pulsinelli's four-vessel occlusion. Rats in the sham operation group and the model group were administered with normal saline -(at the daily dose of 10 mL/kg) by gastrogavage, while those in the treated group were administered with YQG (0.32 g/mL, at the daily dose of 10 mL/kg) by gastrogavage. All administration was performed once per day for 8 successive weeks. The expression of CD11b in CA1 region of hippocampus of vascular dementia rats was detected at week 1, 2, 4, and 8, respectively. RESULTS: Compared with the sham operation group, the expression of CD11b in CA1 region of hippocampus of vascular dementia rats were significantly enhanced in the model group at each time point (P < 0.01). Compared with the model group, the expression of CD11b in CA1 region of hippocampus of vascular dementia rats significantly decreased in the treated group at each time point (P < 0.01), especially at week 2. CONCLUSION: Obvious activation and proliferation of microglias could be seen in CA1 region of hippocampus of vascular dementia rats, and YQG could inhibit activation and proliferation of microglias. PMID- 27386659 TI - [Effect of Jinwu Jiangu Recipe on Expressions of NF-kappaB and IL-17 in Collagen Induced Arthritis Model Rats]. AB - OBJECTIVE: To explore the effect of Jinwu Jiangu Recipe (JJR) on the expression of synovial cells' nuclear factor-kappaB (NF-kappaB) and serum interleukin 17 (IL 17) in collagen induced arthritis (CIA) rats. METHODS: Totally 60 Wistar rats were randomly divided into 6 groups, i.e., the blank control group, the model group, high, middle, and low dose JJR treatment groups, and the tripterygium control group, 10 in each group. Except rats in the blank control group, CIA model was established in rats of the rest 5 groups. Then they were treated from the 7th day of modeling. After 4 weeks of medication they were sacrificed, serum collected, and synovium of joints were isolated. The expression of serum IL-17 was detected in synovium of joints by enzyme linked immunosorbent assay (ELISA). And the expression of NF-kappaB/P65, Ikappabetaalpha and NF-KappaB/P50 were detected by Western blot. RESULTS: Compared with the blank control group, the serum IL-17 level increased in the model group (P <0. 01). Compared with the model group, the serum IL-17 level obviously decreased in high and middle dose JJR groups and the tripterygium control group (P < 0.01). Results of Western blot showed, when compared with the blank control group, protein activities of NF kappaB/P65 and NF-kappaB/P50 were significantly enhanced in the model group (P < 0.01). Compared with the model group, protein activities of NF-kappaB/P65 and NF kappaB/P50 significantly decreased in high and middle dose JJR groups and the tripterygium control group (P < 0.05, P < 0.01). All indices mentioned above were higher in the low dose JJR group than in the tripterygium control group (P < 0.05, P < 0.01). CONCLUSION: JJR could lower the expression of serum IL-17 in CIA model rats, and inhibit protein activities of NF-kappaB/P65 and NF-kappaB/P50. PMID- 27386660 TI - [Progress of Chinese Medicine and Pharmacy Mechanism for Treating Functional Dyspepsia]. PMID- 27386661 TI - EBOLA in America: An Epidemic or a Pandemic? PMID- 27386662 TI - Knowledge, Beliefs and Feelings about Breast Cancer: The Perspective of African American Women. AB - A naturalistic qualitative research study was conducted focusing on young African American women with breast cancer and their biological mothers. Semistructured interviews were conducted with 14 participants to identify their knowledge, beliefs and feelings of breast cancer. Several women reported issues of medical distrust; limited treatment options; breast cancer is a death warrant. Social support was essential for survival. Implications of the research for nursing education and the medical profession are discussed. PMID- 27386664 TI - Visiting the Republic of Cuba: An Experience to Remember. AB - A few years ago, I was privileged to visit the Republic of Cuba as a summer vacation. Officially, this Spanish island is the largest island in the Caribbean, with more than 12 million people. It is only second as being most populous after Hispaniola with its people, culture and customs. Havana is the capital and Cuba's largest city. The United States lies to the immediate north only about 95 miles away, and the Bahamas and Mexico to the west, the Cayman Islands and Jamaica are on the southern end, and Haiti and the Dominion Republic are in the southeastern area. The history of this island is truly amazing. I was able to vist a hospital, and ride public transportation (bus). The trip was made at the time when Cuba was not open to travelers coming direct from the United States. I traveled to Montreal, Canada to board Cabana Arlines to Havana, Cuba. PMID- 27386663 TI - Mothers' Perceptions of Child Vulnerability in Previous Preterm Infants. AB - This research examined whether the same predictive variables of mothers'perceptions of child vulnerability are present for extremely low birth weight (ELBW) and very low birth-weight (VLBW) infants. Data were collected using 120 infants and 119 mothers. In ELBW infants, days until first bottle feeding, feeding problems, and feeding practices accounted for 69.9% of the variance (p < .001) at four months; feeding problems 49.9% (p < .001) at six months; and days until the first bottle feeding and feeding problems were 41.9% (p < .001) at twelve months. In the VLBW infants, feeding problems and length of stay accounted for 46.9% of the variance (p < .001) at four months; infant length of stay was 15.1% (p < .001) at six months; and there was no significance at twelve months. Mothers' perceptions of child vulnerability can be predicted at four, six and twelve months. The predictive variables may depend on the birth weight category of the infant. PMID- 27386665 TI - Measles in Memphis. PMID- 27386666 TI - Chikungunya in Mississippi: The Health Department Response to Imported Cases. AB - Chikungunya (CHIK), a newly recognized mosquito-borne disease in the Western Hemisphere, has resulted in well over a million cases since December 2013. Only about a dozen locally-acquired cases thus far have been reported in the U. S. (Florida), but approximately 1500 imported cases have been seen in returning travelers from the Caribbean and Central and South America. Public health officials are concerned that imported cases may lead to infection of local mosquitoes and, thus disease transmission. This paper documents 9 confirmed CHIK cases in Mississippi: 5 resulting from travel to the Dominican Republic, 2 from Haiti, 1 from Honduras, and 1 from Puerto Rico. In addition, the Mississippi State Department of Health response to those cases is presented and discussed. PMID- 27386667 TI - Top 10 Facts You Should Know about Hearing Loss and Cognitive Decline. PMID- 27386668 TI - You are the Guardians at the Gate. PMID- 27386669 TI - [Not Available]. PMID- 27386670 TI - [Not Available]. PMID- 27386671 TI - [DESCRIPTION OF A RETROPERITONEAL ACCESS ROUTE TO THE VESSELS OF THE SPLEEN FOR SPLENORENAL ARTERIAL AND VENOUS ANASTOMOSIS]. AB - To perform arterial or venous spleno-renal anastomoses, surgeons have so far systematically used the transperitoneal way whic is burdened by a high mortality an morbility percentage. On the basis of anatomo-surgical considerations, a retroperitoneal approach has been found reaching the hilus of the spleen via the lumbar region; the first arterial spleno-renal anastomosis by this way was performed in 1972 and the first venous spleno-renal anastomosis due to portal hipertension also by this way was performed in 1974, the alter proving to be the least aggresive by avoiding damaging the pancreas, the most surgical and direct for reaching the splenic vessels thereby enabling a better exposure and an easier performing of the anastomoses. By being retroperitoneal, the loss or infeccion of the ascitic liquid in the cirrhotic patient is prevented. PMID- 27386672 TI - [BODY AND CORPORALITY IN THE HUMAN BEING: SOME INTERDISCIPLINARY REFLECTIONS]. AB - The major purpose of this contribution is to illustrate some differential aspects between the human and the animal bodies, in order to understand the main distinctive characteristic of the human being: his or her rationality. Thus, we firstly deal with some considerations about the general anthropological framework in which the human body is going to be analysed. Next, we briefly explain the importance of the body for an adequate understanding of the intimacy and the biographical perspectives of the person. Here we show some examples of the altered human corporality to stress the importance of the relation to oneself and others as a key and fundamental aspect to look at our rational corporality. PMID- 27386673 TI - [LIGHT AND SHADOWS OF PSYCHIATRIC NOSOLOGY]. AB - Psychiatry is going through a deep crisis, both as a scientific discipline as a medical specialty. In the present paper we consider in length what we consider to be the two aspects that could explain the situation: the recurring disappointment with classification systems and the persistence of a localizacionism inadequate to explain normal and pathological behavior. Psychiatry lacks a definition of mental disorder that covers all situations, there are difficulties in drawing a precise distinction between normality and psychopathology, and the majority of these "diagnostic" categories are not validated by biological criteria. Furthermore, there is still a debate on the nature of the symptoms of mental disorders, a confusion classification and diagnosis and a preoccupation with the growing inflation of diagnostic categories. Localizationism, that is, the approach to brain function considering that particular pychological functions are carried out by particular brain areas or centers, helps to understand many clinical and psychological phenomena, but have largely failed to explaining the nature of most mental disorders. The crisis should be confronted by putting emphasis on psychopathology instead than in classification, in functions rather than in diagnostic criteria, to be aware in the progress in neuroscientific monistic perspectives and by importing the methods of the emerging connectomics. PMID- 27386674 TI - [THE GLOBAL AND ECONOMIC CRISIS. AND HEALTH MANAGEMENT]. AB - The Global and economic crisis and Health Management The Health care process discussed are 4 steps: assessment, planing, intervention and evaluation. The identify association between social factors linked to social vulnerability (socio economic status, unemployed, poverty) and objective health relate quality of life. The poverty rate is 24.2%, unemployed 26.26%, youth unemployed 56.13%.ratio worker/retired 2.29. Debts 100% GDP The health inequality influence on health related quality of life. The Health System efficiency index. according Bloomber rate (2,013) Spain is 5 degrees in the world, points 68.3 on 100, for the life expectancy 82.3 years, the personal cost of health care 2,271?. Health care 10% GDP (public 7%,private 3%), SS protected population 92.4%, retired person cost 9.2% GDP, p. capita GDP 23,737?. Cost of Care: Hospital/specialist 54%, P. Care 15%, Pharmaceutical 19.8%, P. Health 3.1%. PMID- 27386675 TI - [THE MICROSCOPIC ALGAE AS HUMAN PATHOGENS]. AB - Some microscopic algae can cause different infectious diseases in humans, including skin, bone, and disseminated. These little-known emerging disease are more severe in immunocompromised patients. The confirmatory microbiological diagnosis must be done differential with yeast-like fungi that can be confused. Anti-fungal drugs and surgery, being quite frequent treatment failure have been used in the treatment. Given the increase of immunosuppression in the current medicine and new possibilities of microbiological diagnostics, it is logical that these diseases tend to increase, by which all physician should know them. PMID- 27386676 TI - [PASSIVE TACTILE STIMULATION AS A WAY OF SPATIAL RECOGNITION IN SUBJECTS WITH SEVERE VISUAL IMPAIRMENT OR BLINDNESS]. AB - Regular tactile passive stimulation increases the lasting activation of a greater number of synaptic connections (neuroplasticity) in posterior cortical areas in subjects with blidness with duration and permanence of the neuroplasticity process. Assuming that the lack of stimulation logically involves a deficit due to the cerebral hypofunctionality; in the case of blind subjects such deficit should be more pronounced in the occipital lobe responsible of human vision. We found, after long period of tactile stimulation, that the occipital lobe was activated while having at the same time a visual "qualia" subjective sensation using transcranial magnetic stimulation occipital lobe inhibition decreases visual response. PMID- 27386677 TI - [ANTIAGING TREATMENTS: WHAT ARE WE TALKING ABOUT?]. AB - Antiaging medicine is nowadays an equivocal topic frequently used in geriatric medicine. It is, also, one of the most important sources of medical costs. With the words "antiaging medicine" we may express several different desires: a) to arrive at advanced age in the best possible physical and mental conditions, b) to act in order to slowing the aging process associated changes, c) to revert some of these negative changes. Prevention is the only positive successful way to achieve any of these possibilities. It means to emphasize any sort on interventions acting over health habits as physical activity, nutrition, to avoid toxic habits (tobacco) and to take primary and secondary diseases preventive measures. There is not medical evidence of effectiveness with any other measures, as hormonal therapies or reconstructive surgery. PMID- 27386679 TI - [FROM THE CT-PET TO THE MRI-PET]. AB - CT-PET is a multimodality imaging technique which diagnostic utility has been demostrated especially in oncology and neurosciences. There is about 100 equipments of this modality in Spain. MRI-PET ia a new multimodality imaging technique recently installed in Spain. Its main advantages over CT-PET are: the reduction in the absorbed dose of radiations and the better contrast between normal and pathological tissues, especially in soft tissue tumors and neurological disorders. PMID- 27386678 TI - [THE THALAMIC DOPAMINERGIC SYSTEM. A NOVEL SYSTEM IN THE PRIMATE BRAIN]. AB - The human and macaque monkey thalamus receives an abundant dopamine innervation, as revealed by immunolabeling of axons for molecules specific for the dopaminergic phenotype. The distribution of the innervation is highly heterogeneous, with specific association, limbic and motor nuclei receiving the densest innervation. The origin of thalamic dopamine is multiple; it includes dopaminergic nuclei in the hypothalamus, periaqueductal gray, ventral mesencephalon and lateral parabrachial nucleus. This novel dopaminergic system, notably developed in the primate brain, is rudimentary in rodents. Studying the thalamic dopaminergic system in primates opens new avenues for understanding neurological and psychiatric conditions. PMID- 27386680 TI - [RADIATION ONCOLOGY: CONTEXT IN CANCER MEDICINE AND CLINICAL TRASLATIONAL RESEARCH MODELS]. AB - Radiation Oncology is a clinical speciality supported by technological development including biomedical imaging, ionizing radiation generators and radiobiology of cancer and normal tissues. Translational research and development opportunities incorporate clinical models available in hospital practice with academic interest in health care innovative approaches. Examples of mature research projects in translational radiation oncology are described: a) molecular imaging and expression for radioresponse assessment; b) oligorecurrent cancer results after rescue surgery and intensified radiotherapy; c) stereotactic surgical navigation for intraoperative radiotherapy. PMID- 27386681 TI - [CONGENITAL ADRENAL HYPERPASIA]. AB - It is presented the clinical and physiopathological characteristics of most relevant CAH during pediatric ages. Also it is discussed the dauting benefit derived from analysing in all newborns 17-OH-progesterone in a few blood drops embedded filter-paper. In addition it is emphasized the interest of treating risk pregnancies before delivery. PMID- 27386682 TI - [MEDICINE IN THE LITERARY WORK OF MIGUEL TORCA]. AB - Miguel Torga (Sao Martinho de Anta 1907 - Coimbra 1995) was one of the most important portuguese writers of the twentieth century. There is such identity between his medical and literary activity that he used to say that "his own hand not only writes but also prescribes". Reading his work, mainly autobiographical, allows us to analyze their vision of medicine, the patient physician relationship and how a doctor lives his own disease. In the first case medicine constitute an essential tool to help nature and, therefore, an instrument that makes hope possible. In the second case indicates that in the patient physician relationship are present sadness, stress, anxiety and a supreme exercise of the human condition which is the anamnesis when the patients open their intimity to the doctor. In the third case Torga's work illustrates how a physician can live his own illness as an advantage, as a judicial sentence or as a possibility. Approaching to the medicine under perspective of Miguel Torga, doctor and writer, will help us to understand medicine in a more human context in which the life of the doctor is not stranger to their patients, or to the nature and the concrete world that both share. PMID- 27386683 TI - [THE FRENCH ANATOMICAL XAVIER BICHAT (1771 - 1802). FUNDATOR OF DOCTRINE OF TISSUES. BIOGRAPHICAL MEMORY BEFORE HIS GRAVE]. AB - It is reminded to Marie Francois Xavier Bichat (1771-1802), French physician who figure in the pages of the history of the Universal Medicine. With him begins the anatomic mentality in the nineteenth century, which in 1801 introduced the concept of tissue in his book "Anatomie Generale". With unprecedented nature is disclosed his tomb in Paris' Pere Lachaise cemetery visited by the author, fact that motivated before it about his memories and historical work, which appears in the communication, as a tribute to his memory. PMID- 27386684 TI - [MEDICOLEGAL ASSESSMENT OF THE AGGRESSOR TO PREVENT ADVERSE OUTCOMES IN WOMEN VIOLENCE]. AB - Violence against women is a health care problem because it is very prevalent and its consequences are serious. The number of deaths due to this problem keep being alarming. Measures to prevent this could be:--Make victims and their families know that complaint is very important.--After complaint, protect the victim and solve her situation quickly. A medicolegal assessment is needed, with a medical psychological-and psychiatric exploration of the aggressor, to detect alcohol or substances abuse, and to know his personality profile. Risk features are emotional instability, suspicion, pride, sense of abandonment, sense of injustice about the complaint, anxiety, emotional stress or depression. These features mean risk of lethal or very serious damage. Anxiety and depression can also means homicide followed by suicide of the aggressor. An adequate and early medico-legal assessment of the possible aggressor can prevent these adverse outcomes. PMID- 27386685 TI - [OROPHARYS CANCER: THE SQUAMOUS CELL]. AB - The Diffuse Large B-Cell Lymphoma is the most frequent non Hodgkin Lymphoma. The role of CT/PET in this relatively homogeneous group of lymphomas is controversial. It rarely changes the management of the patients in the initial staging. Recents publications, clinical trials and experts consensus meetings have demonstrated its utility in the evaluation of the response at the end of the treatment. The interest of CT/PET in the evaluation of the response during the treatment, with the objective of implement a "Risk Adapted Therapy", in increasing. PMID- 27386686 TI - [NEUROSPIRITUALITY]. AB - Neurospirituality refers to the fact that the brain is able to produce spiritual experiences. The hypothesis put forward here is that the origin of spiritual experiences lies in the hyperactivity of limbic structures within the depth of the temporal lobe. The characteristics of these phenomena are the common denominator of the mystic experiences, the near to death experiences, the symptoms of the temporal lobe epilepsy and those following the consumption of entheogen drugs. Experiments with electromagnetic stimulation of the temporal lobe support this hypothesis since they also induce spiritual experiences. PMID- 27386687 TI - DEALING WITH DISRUPTIVE PHYSICIANS. PMID- 27386688 TI - How do you motivate employees who are maxed out at salary level?. PMID- 27386689 TI - REACHING A 95% COPAY COLLECTION RATE WITH TEAMWORK, PROCESS REVAMPS. PMID- 27386690 TI - Physician-hospital alignment models: An evolving lexicon. PMID- 27386691 TI - Advance care directives bring healthcare full circle for patients, providers. PMID- 27386692 TI - PHOs: An ideal vehicle to create ACOs. PMID- 27386693 TI - Timely patient access affects appointment retention. PMID- 27386694 TI - Cybersecurity: The board's role in oversight. PMID- 27386695 TI - "We must nurture the potential of nurses". PMID- 27386696 TI - England's CNO to launch new nursing framework. PMID- 27386698 TI - 'Strong' support to regulate new nursing role. PMID- 27386697 TI - Nurse procurement experts hope to save millions and improve care. PMID- 27386699 TI - DH reveals ambition to reform professional regulation system. PMID- 27386700 TI - Nurse-led scheme launched to ensure consistent high-quality care. PMID- 27386701 TI - Bursary removal could reduce nursing applications, warn MPs. PMID- 27386702 TI - Students 'go digital' with training in vital signs monitoring system. PMID- 27386703 TI - Risk of patients getting 'harmful' levels of oxygen. PMID- 27386705 TI - "Nurses who become ACPs should not be mini medics". PMID- 27386704 TI - "Nursing and patients will suffer if there are no nurses in the DH". PMID- 27386706 TI - Changing our view of older people's continence care. AB - An assumption is often made that incontinence is inevitable in older people, or those with dementia or other long-term conditions. However, research has highlighted strategies that can help them to remain continent. A working group was established to develop a resource to promote continence for people with dementia and long-term conditions. This article explores the resource's key messages, as well as the importance of changing how incontinence is viewed, and what health professionals and the public expect of continence services. PMID- 27386707 TI - Childhood incontinence: risk factors and impact. AB - Continence problems in children can persist into later childhood and have a serious effect on quality of life. Research into its causes and impact is scarce, and useful resources are limited. A Medical Research Council grant is funding a project at the University of Bristol, which aims to improve understanding of the risk factors and outcomes of continence problems in children and adolescents. This article outlines the initial findings, which could help in the production of resources for parents, children and young people. PMID- 27386708 TI - Managing the weaning of a temporary tracheostomy. AB - The second article of this four-part series on tracheostomy care describes the process of weaning patients off a tracheostomy, decannulation of the tube and aftercare. The role of the multidisciplinary team is discussed, as well as the importance of psychological care of patients who may be anxious about their ability to breathe without a tube. PMID- 27386710 TI - 60 seconds with Julie Hamilton. PMID- 27386709 TI - Identifying the learning needs of senior nurses. AB - There has been a drive to encourage nurses into positions of leadership but, despite the importance of considering how the senior nurse role should be developed and the needs of senior nurses, little literature exists on the subject. To explore senior nurse development, one health. board in Scotland invited senior nurses to participate in a "development conversation". Key points were noted during each conversation and themed. This article outlines the needs identified and explores how they could be addressed. PMID- 27386711 TI - Fieldworking from home. PMID- 27386712 TI - EDITORIAL. PMID- 27386714 TI - A YANKEE AT OXFORD: JOHN WILLIAM DRAPER AT THE BRITISH ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE AT OXFORD, 30 JUNE 1860. AB - This paper contributes to the revisionist historiography on the legendary encounter between Samuel Wilberforce and Thomas Henry Huxley at the 1860 meeting in Oxford of the British Association for the Advancement of Science. It discusses the contents of a series of letters written by John William Draper and his family reflecting on his experience at that meeting. The letters have recently been rediscovered and have been neither published nor examined at full length. After a preliminary discussion on the historiography of the Oxford debate, the paper discloses the contents of the letters and then assesses them in the light of other contemporary accounts. The letters offer a nuanced reinterpretation of the event that supports the growing move towards a revisionist account. PMID- 27386713 TI - AN AUTOPSIC ART: DRAWINGS OF 'DR GRANVILLE'S MUMMY' IN THE ROYAL SOCIETY ARCHIVES. AB - In 1821 Augustus Bozzi Granville FRS unwrapped and dissected an ancient Egyptian mummy, presenting the results of his examination to the Royal Society in 1825. He commissioned artist Henry Perry to draw the process in stages; these drawings were subsequently engraved by James Basire for publication in Philosophical Transactions. This article presents the original drawings for the first time, allowing comparison with their engravings. Taken together with Granville's accounts of the unwrapping of the mummy, the drawings demonstrate the significant role of illustration and other visual practices in anatomical argumentation in the early nineteenth century, as well as the prestige that commissioned illustrations lent to the performance and dissemination of scientific expertise. Moreover, the drawings include one of the key visual tropes of race science--a skull in left-facing profile, mapped with a facial angle--and thus indicate the early incorporation of Egyptian mummies into typologies of race. PMID- 27386715 TI - 'DIRTY WORK', BUT SOMEONE HAS TO DO IT: HOWARD P. ROBERTSON AND THE REFEREEING PRACTICES OF PHYSICAL REVIEW IN THE 1930S. AB - In the 1930s the mathematical physicist Howard P. Robertson was the main referee of the journal Physical Review for papers concerning general relativity and related subjects. The rich correspondence between Robertson and the editors of the journal enables a historical investigation of the refereeing process of Physical Review at the time that it was becoming one of the most influential physics periodicals in the world. By focusing on this case study, the paper investigates two complementary aspects of the evolution of the refereeing process: first, the historical evolution of the refereeing practices in connection with broader contextual changes, and second, the attempts to define the activity of the referee, including the epistemic virtues required and the journal's functions according to the participants' categories. By exploring the tension between Robertson's idealized picture about how the referee should behave and the desire to promote his intellectual agenda, I show that the evaluation criteria that Robertson employed were contextually dependent and I argue that, in the 1930s, through his reports the referee had an enormous power in defining what direction future research should take. PMID- 27386716 TI - ANDREWES'S CHRISTMAS FAIRY TALE: ATYPICAL THINKING ABOUT CANCER AETIOLOGY IN 1935. AB - This paper uses a short 'Christmas fairy-story for oncologists' sent by Christopher Andrewes with a 1935 letter to Peyton Rous as the centrepiece of a reflection on the state of knowledge and speculation about the viral aetiology of cancer in the 1930s. Although explicitly not intended for public circulation at the time, the fairy-story merits publication for its significance in the history of ideas about viruses, which are taken for granted today. Andrewes and Rous were prominent members of the international medical research community and yet faced strong resistance to their theory that viruses could cause such tumours as chicken sarcomas and rabbit papillomas. By looking at exchanges between these men among themselves and other proponents of their theories and with their oncologist detractors, we highlight an episode in the behind-the-scenes workings of medical science and show how informal correspondence helped keep alive a vital but then heterodox idea about the role of viruses in causing cancer. PMID- 27386718 TI - FDA Implements New Labeling for Medications Used During Pregnancy and Lactation. PMID- 27386721 TI - Common Questions About Streptococcal Pharyngitis. AB - Group A beta-hemolytic streptococcal (GABHS) infection causes 15% to 30% of sore throats in children and 5% to 15% in adults, and is more common in the late winter and early spring. The strongest independent predictors of GABHS pharyngitis are patient age of five to 15 years, absence of cough, tender anterior cervical adenopathy, tonsillar exudates, and fever. To diagnose GABHS pharyngitis, a rapid antigen detection test should be ordered in patients with a modified Centor or FeverPAIN score of 2 or 3. First-line treatment for GABHS pharyngitis includes a 10-day course of penicillin or amoxicillin. Patients allergic to penicillin can be treated with firstgeneration cephalosporins, clindamycin, or macrolide antibiotics. Nonsteroidal anti-inflammatory drugs are more effective than acetaminophen and placebo for treatment of fever and pain associated with GABHS pharyngitis; medicated throat lozenges used every two hours are also effective. Corticosteroids provide only a small reduction in the duration of symptoms and should not be used routinely. PMID- 27386723 TI - Diagnosis and Management of Vertebral Compression Fractures. AB - Vertebral compression fractures (VCFs) are the most common complication of osteoporosis, affecting more than 700,000 Americans annually. Fracture risk increases with age, with four in 10 white women older than 50 years experiencing a hip, spine, or vertebral fracture in their lifetime. VCFs can lead to chronic pain, disfigurement, height loss, impaired activities of daily living, increased risk of pressure sores, pneumonia, and psychological distress. Patients with an acute VCF may report abrupt onset of back pain with position changes, coughing, sneezing, or lifting. Physical examination findings are often normal, but can demonstrate kyphosis and midline spine tenderness. More than two-thirds of patients are asymptomatic and diagnosed incidentally on plain radiography. Acute VCFs may be treated with analgesics such as acetaminophen, nonsteroidal anti inflammatory drugs, narcotics, and calcitonin. Physicians must be mindful of medication adverse effects in older patients. Other conservative therapeutic options include limited bed rest, bracing, physical therapy, nerve root blocks, and epidural injections. Percutaneous vertebral augmentation, including vertebroplasty and kyphoplasty, is controversial, but can be considered in patients with inadequate pain relief with nonsurgical care or when persistent pain substantially affects quality of life. Family physicians can help prevent vertebral fractures through management of risk factors and the treatment of osteoporosis. PMID- 27386722 TI - Cardiac Rehabilitation: Improving Function and Reducing Risk. AB - Cardiac rehabilitation is a comprehensive multidisciplinary program individually tailored to the needs of patients with cardiovascular disease. The overall goals focus on improving daily function and reducing cardiovascular risk factors. Cardiac rehabilitation includes interventions aimed at lowering blood pressure and improving lipid and diabetes mellitus control, with tobacco cessation, behavioral counseling, and graded physical activity. The physical activity component typically involves 36 sessions over 12 weeks, during which patients participate in supervised exercise under cardiac monitoring. There are also intensive programs that include up to 72 sessions lasting up to 18 weeks, although these programs are not widely available. Additional components of cardiac rehabilitation include counseling on nutrition, screening for and managing depression, and assuring up-to-date immunizations. Cardiac rehabilitation is covered by Medicare and recommended for patients following myocardial infarction, bypass surgery, and stent placement, and for patients with heart failure, stable angina, and several other conditions. Despite proven benefits in mortality rates, depression, functional capacity, and medication adherence, rates of referral for cardiac rehabilitation are suboptimal. Groups less likely to be referred are older adults, women, patients who do not speak English, and persons living in areas where cardiac rehabilitation is not locally available. Additionally, primary care physicians refer patients less often than cardiologists and cardiothoracic surgeons. PMID- 27386724 TI - Pruritic Rash on the Forearm and Legs. PMID- 27386725 TI - Procalcitonin-Guided Antibiotic Therapy for Acute Respiratory Infections. PMID- 27386729 TI - Topical NSAIDs for Acute Musculoskeletal Pain in Adults. PMID- 27386730 TI - Strep Throat. PMID- 27386731 TI - Reversible Structural Swell-Shrink and Recoverable Optical Properties in Hybrid Inorganic-Organic Perovskite. AB - Ion migration in hybrid organic-inorganic perovskites has been suggested to be an important factor for many unusual behaviors in perovskite-based optoelectronics, such as current-voltage hysteresis, low-frequency giant dielectric response, and the switchable photovoltaic effect. However, the role played by ion migration in the photoelectric conversion process of perovskites is still unclear. In this work, we provide microscale insights into the influence of ion migration on the microstructure, stability, and light-matter interaction in perovskite micro/nanowires by using spatially resolved optical characterization techniques. We observed that ion migration, especially the migration of MA(+) ions, will induce a reversible structural swell-shrink in perovskites and recoverably affect the reflective index, quantum efficiency, light-harvesting, and photoelectric properties. The maximum ion migration quantity in perovskites was as high as approximately 30%, resulting in lattice swell or shrink of approximately 4.4%. Meanwhile, the evidence shows that ion migration in perovskites could gradually accelerate the aging of perovskites because of lattice distortion in the reversible structural swell-shrink process. Knowledge regarding reversible structural swell-shrink and recoverable optical properties may shed light on the development of optoelectronic and converse piezoelectric devices based on perovskites. PMID- 27386732 TI - Identification of Targets of the HIF-1 Inhibitor IDF-11774 Using Alkyne Conjugated Photoaffinity Probes. AB - We developed a hypoxia-inducible factor-1 (HIF-1) inhibitor, IDF-11774, as a clinical candidate for cancer therapy. To understand the mechanism of action of IDF-11774, we attempted to isolate target proteins of IDF-11774 using bioconjugated probes. Multifunctional chemical probes containing sites for click conjugation and photoaffinity labeling were designed and synthesized. After fluorescence and photoaffinity labeling of proteins, two-dimensional electrophoresis (2DE) was performed to isolate specific molecular targets of IDF 11774. Heat shock protein (HSP) 70 was identified as a target protein of IDF 11774. We revealed that IDF-11774 inhibited HSP70 chaperone activity by binding to its allosteric pocket, rather than the ATP-binding site in its nucleotide binding domain (NBD). Moreover, IDF-11774 reduced the oxygen consumption rate (OCR) and ATP production, thereby increasing intracellular oxygen tension. This result suggests that the inhibition of HSP70 chaperone activity by IDF-11774 suppresses HIF-1alpha refolding and stimulates HIF-1alpha degradation. Taken together, these findings indicate that IDF-11774-derived chemical probes successfully identified IDF-11774's target molecule, HSP70, and elucidated the mode of action of IDF-11774 in inhibiting HSP70 chaperone activity and stimulating HIF-1alpha degradation in cancer cells. PMID- 27386733 TI - Follow your nose: Implicit spatial processing within the chemosensory systems. AB - Although most studies agree that humans cannot smell in stereo, it was recently suggested that olfactory localization is possible when assessed implicitly. In a spatial cueing paradigm, lateralized olfactory cues impaired the detection of congruently presented visual targets, an effect contrary to the typical facilitation observed in other sensory domains. Here, we examined the specificity and the robustness of this finding by studying implicit localization abilities in another chemosensory system and by accounting for possible confounds in a modified paradigm. Sixty participants completed a spatial cueing task along with an explicit localization task, using trigeminal (Experiment 1) and olfactory (Experiment 2) stimuli. A control task was implemented to control for residual somatosensory stimulation (Experiment 3). In the trigeminal experiment, stimuli were localized with high accuracy on the explicit level, while the cueing effect in form of facilitation was limited to response accuracy. In the olfactory experiment, responses were slowed by congruent cues on the implicit level, while no explicit localization was observed. Our results point to the robustness of the olfactory interference effect, corroborating the implicit-explicit dissociation of olfactory localization, and challenging the view that humans lost the ability to extract spatial information from smell. The absence of a similar interference for trigeminal cues suggests distinct implicit spatial processing mechanisms within the chemosensory systems. Moreover, the lack of a typical facilitation effect in the trigeminal domain points to important differences from spatial information processing in other, nonchemosensory domains. The possible mechanisms driving the effects are discussed. (PsycINFO Database Record PMID- 27386735 TI - Future Papers. PMID- 27386734 TI - Remote Plasma Oxidation and Atomic Layer Etching of MoS2. AB - Exfoliated molybdenum disulfide (MoS2) is shown to chemically oxidize in a layered manner upon exposure to a remote O2 plasma. X-ray photoelectron spectroscopy (XPS), low energy electron diffraction (LEED), and atomic force microscopy (AFM) are employed to characterize the surface chemistry, structure, and topography of the oxidation process and indicate that the oxidation mainly occurs on the topmost layer without altering the chemical composition of underlying layer. The formation of S-O bonds upon short, remote plasma exposure pins the surface Fermi level to the conduction band edge, while the MoOx formation at high temperature modulates the Fermi level toward the valence band through band alignment. A uniform coverage of monolayer amorphous MoO3 is obtained after 5 min or longer remote O2 plasma exposure at 200 degrees C, and the MoO3 can be completely removed by annealing at 500 degrees C, leaving a clean ordered MoS2 lattice structure as verified by XPS, LEED, AFM, and scanning tunneling microscopy. This work shows that a remote O2 plasma can be useful for both surface functionalization and a controlled thinning method for MoS2 device fabrication processes. PMID- 27386736 TI - Paroxysmal sympathetic hyperactivity: Autonomic instability and muscle over activity following severe brain injury. AB - BACKGROUND: Children who suffer from moderate-to-severe brain injury can develop a complicating phenomenon known as paroxysmal sympathetic hyperactivity (PSH), characterized by autonomic instability and identified clinically as a cluster of symptoms that can include recurrent fever without a source of infection, hypertension, tachycardia, tachypnea, agitation, diaphoresis and dystonia. Studies with adults have demonstrated that this cluster of symptoms is associated with poorer clinical outcomes (prolonged hospitalizations, poorer cognitive and motor function). However, there have been limited studies in children with PSH. OBJECTIVE: To present a literature review regarding PSH following severe brain injury and highlight research needs in children with PSH. METHODOLOGY: Electronic databases (CINAHL, Ovid Medline, Web of Science and Google Scholar) were searched. RESULTS: Thirty-one research articles met the criteria for inclusion. Several themes emerged regarding the phenomenon of interest during the review: nomenclature, symptoms, management and differences between children and adults. IMPLICATIONS: The majority of the research regarding PSH following severe brain injury has been descriptive in nature. Few studies, however, have explored PSH in children with brain injury; therefore, little is known about whether the outcomes of children with PSH are different and, if so, in what ways. PMID- 27386737 TI - Interconversion of Peptide Mass Spectral Libraries Derivatized with iTRAQ or TMT Labels. AB - Derivitization of peptides with isobaric tags such as iTRAQ and TMT is widely employed in proteomics due to their compatibility with multiplex quantitative measurements. We recently made publicly available a large peptide library derived from iTRAQ 4-plex labeled spectra. This resource has not been used for identifying peptides labeled with related tags with different masses, because values for virtually all masses of precursor and most product ions would differ for ions containing the different tags as well as containing different tag specific peaks. We describe a method for interconverting spectra from iTRAQ 4 plex to TMT (6- and 10-plex) and to iTRAQ 8-plex. We interconvert spectra by appropriately mass shifting sequence ions and discarding derivative-specific peaks. After this "cleaning" of search spectra, we demonstrate that the converted libraries perform well in terms of peptide spectral matches. This is demonstrated by comparing results using sequence database searches as well as by comparing search effectiveness using original and converted libraries. At 1% FDR TMT labeled query spectra match 97% as many spectra against a converted iTRAQ library as compared to an original TMT library. Overall this interconversion strategy provides a practical way to extend results from one derivatization method to others that share related chemistry and do not significantly alter fragmentation profiles. PMID- 27386738 TI - Cytotoxic cardenolides and sesquiterpenoids from the fruits of Reevesia formosana. AB - Bioassay-guided fractionation of the fruits of Reevesia formosana led to isolation of three cardenolides (reevesioside J, reevesioside K, and epi reevesioside K), three sesquiterpenoids (reevesiterpenol C, reevesiterpenol D, and reevesiterpenol E), and two glycosides (reevesianin A and reevesianin B), along with 46 known compounds. Their structures were determined using spectroscopic techniques. In addition to the reported cytotoxic cardenolides, reevesioside J and strophanthidin exhibited moderate cytotoxicity against the cell lines MCF-7, NCI-H460, and HepG2, with IC50 values of 0.39 +/- 0.06 MUM and 1.06 +/- 0.12 MUM for MCF-7, 0.12 +/- 0.01 MUM and 0.29 +/- 0.01 MUM for NCI H460, and 1.09 +/- 0.02 MUM and 1.72 +/- 0.02 MUM for HepG2, respectively. Reevesiterpenol E also exhibited the best selective cytotoxicity to the NCI-H460 cell line, with an IC50 value of 3.15 +/- 0.22 MUM. PMID- 27386739 TI - Prevalence and factors associated with discordant intima-media thickness and arterial stiffness combined measurements in people living with HIV. PMID- 27386740 TI - Social connectedness and life satisfaction: Comparing mean levels for 2 undergraduate samples and testing for improvement based on brief counseling. AB - OBJECTIVES: Comparing the mean levels of social connectedness and life satisfaction, and analyzing their relationship for 2 undergraduate samples, and testing for an increase in their means for a brief counseling sample. PARTICIPANTS: Between October 2013 and May 2015, 3 samples were collected: not-in counseling (NIC; n = 941), initial counseling session (ICS; ie, triage session only; n = 168), and brief counseling (BC; ie, median of 4 additional counseling sessions; n = 28). METHODS: Online surveys measuring demographic and background control variables, social connectedness, and life satisfaction. RESULTS: NIC students exhibited higher social connectedness and life satisfaction than ICS students. Social connectedness significantly explained life satisfaction beyond controlled-for variables for both samples. There was a significant increase in social connectedness and life satisfaction for the BC sample. CONCLUSIONS: Social connectedness is an important antecedent of life satisfaction for undergraduates. Brief counseling can increase transition students' social connectedness and life satisfaction. PMID- 27386741 TI - Unmet Learning Needs of Physicians in Specialty Training in Palliative Care: A Japanese Nationwide Study. AB - BACKGROUND: Despite the urgent need for a quality training system in palliative care, learning needs among physicians in palliative care specialty training have not been systematically explored in Japan. AIM: To clarify unmet learning needs among Japanese physicians in specialty training in palliative care and the potential solutions they favor to meet those needs. DESIGN: A Japanese nationwide survey. SETTING/PARTICIPANTS: Participants were physicians in specialty training in palliative care. The questionnaire included unmet learning needs and potential solutions. Factor analysis was performed to identify underlying subscales of unmet needs. RESULTS: In total, 253 of 735 institutions (34%) responded; of 284 physicians, 253 (89%) responded and 229 were eligible. The most prevalent unmet needs included the following: "to learn areas other than medicine" (89%), "to obtain research support from a data center" (87%), and "to learn ways to educate students and residents about palliative medicine" (87%). The potential solutions most participants favored to meet those needs included the following: "to develop a comprehensive training program" (74%), "to develop systems which reflect trainees' opinions on the improvement of training programs" (71%), and "to increase the number of training institutions" (69%). CONCLUSION: Physicians in palliative care specialty training had markedly unmet needs regarding training on comprehensive contents, education, and research support; they considered increasing the number of comprehensive quality training programs as a potential solution. Our findings may help physicians in palliative care training, faculty physicians, training programs, academic societies, and the government to develop collaborative efforts to fulfill the unmet needs of trainees. PMID- 27386742 TI - Effects of a randomized controlled trial to assess the six-months effects of a school based smoking prevention program in Saudi Arabia. AB - OBJECTIVE: To examine the efficacy of a smoking prevention program which aimed to address smoking related cognitions and smoking behavior among Saudi adolescents age 13 to 15. METHOD: A randomized controlled trial was used. Respondents in the experimental group (N=698) received five in-school sessions, while those in the control group (N=683) received no smoking prevention information (usual curriculum). Post-intervention data was collected six months after baseline. Logistic regression analysis was applied to assess effects on smoking initiation, and linear regression analysis was applied to assess changes in beliefs and analysis of covariance (ANCOVA) was used to assess intervention effects. All analyses were adjusted for the nested structure of students within schools. RESULTS: At post-intervention respondents from the experimental group reported in comparison with those from the control group a significantly more negative attitude towards smoking, stronger social norms against smoking, higher self efficacy towards non-smoking, more action planning to remain a non-smoker, and lower intentions to smoke in the future. Smoking initiation was 3.2% in the experimental group and 8.8% in the control group (p<0.01). CONCLUSION: The prevention program reinforced non-smoking cognitions and non-smoking behavior. Therefore it is recommended to implement the program at a national level in Saudi Arabia. Future studies are recommended to assess long term program effects and the conditions favoring national implementation of the program. PMID- 27386743 TI - Invited Commentary: Corporate social responsibility and public health: An unwanted marriage. PMID- 27386745 TI - Cerebrovascular and cognitive benefits of high-oleic peanut consumption in healthy overweight middle-aged adults. AB - OBJECTIVE: Peanuts contain bioactive nutrients beneficial for vascular function. This study investigated whether consumption of unsalted peanuts (with skins) would enhance cerebrovascular perfusion and cognitive performance. METHOD: In a randomized crossover trial, 61 volunteers (29 males/32 females, 65 +/- 7 years, BMI 31 +/- 4 kg/m2) consumed their habitual diet +/- high-oleic peanuts (56-84 g/day), each for 12 weeks. Nutrient intakes, vascular and cognitive function were assessed at baseline and at the end of each 12-week phase. Differences between the ends of each phase were compared by general linear repeated measures ANOVA controlling for baseline. Pearson's correlation analyses determined relationships between differences in cerebrovascular reactivity (CVR) and cognitive function. RESULTS: Intakes of bioactive nutrients increased during the peanut phase. CVR was 5% greater in the left middle cerebral artery (MCA) and 7% greater in the right MCA. Small artery elasticity was 10% greater after peanut consumption; large artery elasticity and blood pressure did not differ between phases. Measures of short-term memory, verbal fluency, and processing speed were also higher following the peanut phase; other cognitive measures did not change. Differences in CVR in the left MCA correlated with differences in delayed memory and recognition. DISCUSSION: Regular peanut consumption improved cerebrovascular and cognitive function; increased intakes of bioactive nutrients may have mediated these improvements. This clinical trial was registered with the Australian Clinical Trials Registry (ACTRN 12612000192886). PMID- 27386753 TI - The National Early Warning Score: Translation, testing and prediction in a Swedish setting. AB - The National Early Warning Score - NEWS is a "track and trigger" scale designed to assess in-hospital patients' vital signs and detect clinical deterioration. In this study the NEWS was translated into Swedish and its association with the need of intensive care was investigated. A total of 868 patient charts, recorded by the medical emergency team at a university hospital, containing the parameters needed to calculate the NEWS were audited. The NEWS was translated into Swedish and tested for inter-rater reliability with a perfect agreement (weighted kappa=1.0) among the raters. The median score for patients admitted to the ICU were higher than for those who were not (10 vs. 8, p<0.0001). AUROC for discriminating admittance to the ICU was 0.68 (95% CI: 0.622-0.739, p<0.0001). A regression analysis showed that lower oxygen saturation and a lower level of consciousness were significantly associated with ICU admission (OR 1.27 [1.06 1.52], p=0.01 and OR 1.77 [1.12-2.82], p=0.02) and may predict admission to the ICU better than the other parameters. The Swedish translated NEWS seems to have excellent inter-rater reliability and can be used without risk of linguistic misinterpretation. High scores for the parameters oxygen saturation and level of consciousness in the NEWS may predict admission to the ICU. PMID- 27386744 TI - What can errors tell us about body representations? AB - In this review, we examine how tactile misperceptions provide evidence regarding body representations. First, we propose that tactile detection and localization are serial processes, in contrast to parallel processing hypotheses based on patients with numbsense. Second, we discuss how information in primary somatosensory maps projects to body size and shape representations to localize touch on the skin surface, and how responses after use-dependent plasticity reflect changes in this mapping. Third, we review situations in which our body representations are inconsistent with our actual body shape, specifically discussing phantom limb phenomena and anesthetization. We discuss problems with the traditional remapping hypothesis in amputees, factors that modulate perceived body size and shape, and how changes in perceived body form influence tactile localization. Finally, we review studies in which brain-damaged individuals perceive touch on the opposite side of the body, and demonstrate how interhemispheric mechanisms can give rise to these anomalous percepts. PMID- 27386754 TI - Intrauterine Contraception Continuation in Adolescents and Young Women: A Systematic Review. AB - STUDY OBJECTIVE: Adolescents are at high risk for unintended pregnancies. Although intrauterine devices (IUDs), long-acting reversible contraceptives (LARCs), are known to be highly effective in preventing pregnancy, little is known about IUD adherence in adolescents. In this systematic review (SR) we examined IUD continuation rates compared with other forms of contraception in young women aged 25 years and younger. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A systematic search of Ovid Medline, Cochrane Library, and Embase was conducted for the years 1946-2015. Included studies examined IUD use in women 25 years of age and younger, compared IUD use with another form of contraception, and measured continuation rates at 12 months. The quality of each study was appraised using the Downs and Black criteria, and 12-month continuation rates among studies were pooled and analyzed according to contraceptive type. RESULTS: Of 3597 articles retrieved, 9 studies met criteria for SR. Synthesized across studies, 12-month continuation was significantly higher for IUD users (86.5%, 12,761/14,747) compared with oral contraceptives (39.6%, 1931/4873), Depo-Provera (Pfizer Inc, New York, NY) hormonal injection (39.8%, 510/1282), vaginal ring (48.9%, 196/401), and transdermal patch (39.8%, 37/93; all P values < .001). There was no statistically significant difference in 12-month continuation between the IUD and another LARC method, the subdermal etonogestrel implant (85.3%, 4671/5474). CONCLUSION: Findings of this SR suggest that continuation rates for IUDs are generally higher compared with other contraceptive methods for women aged 25 years and younger. In a population with high rates of unintended pregnancies, generally low adherence, and imperfect use with other non-LARCs, IUD use should be encouraged. PMID- 27386755 TI - Neonatal tolerance induction enables accurate evaluation of gene therapy for MPS I in a canine model. AB - High fidelity animal models of human disease are essential for preclinical evaluation of novel gene and protein therapeutics. However, these studies can be complicated by exaggerated immune responses against the human transgene. Here we demonstrate that dogs with a genetic deficiency of the enzyme alpha-l-iduronidase (IDUA), a model of the lysosomal storage disease mucopolysaccharidosis type I (MPS I), can be rendered immunologically tolerant to human IDUA through neonatal exposure to the enzyme. Using MPS I dogs tolerized to human IDUA as neonates, we evaluated intrathecal delivery of an adeno-associated virus serotype 9 vector expressing human IDUA as a therapy for the central nervous system manifestations of MPS I. These studies established the efficacy of the human vector in the canine model, and allowed for estimation of the minimum effective dose, providing key information for the design of first-in-human trials. This approach can facilitate evaluation of human therapeutics in relevant animal models, and may also have clinical applications for the prevention of immune responses to gene and protein replacement therapies. PMID- 27386757 TI - Physical therapy management of infants and children with hypophosphatasia. AB - Hypophosphatasia (HPP) is a rare inborn error of metabolism resulting in undermineralization of bone and subsequent skeletal abnormalities. The natural history of HPP is characterized by rickets and osteomalacia, increased propensity for bone fracture, early loss of teeth in childhood, and muscle weakness. There is a wide heterogeneity in disease presentation, and the functional impact of the disease can vary from perinatal death to gait abnormalities. Recent clinical trials of enzyme replacement therapy have begun to offer an opportunity for improvement in survival and function. The role of physical therapy in the treatment of the underlying musculoskeletal dysfunction in HPP is underrecognized. It is important for physical therapists to understand the disease characteristics of the natural history of a rare disease like HPP and how the impairment and activity limitations may change in response to medical interventions. An understanding of when and how to intervene is also important in order to optimally impact body function, lessen structural impairment, and facilitate increased functional independence in mobility and activities of daily living. Individualizing treatment to the child's needs, medical fragility, and setting (home/school/hospital), while educating parents, caregivers, and school staff regarding approved activities and therapy frequency, may improve function and development in children with HPP. PMID- 27386756 TI - Expression of FBN1 during adipogenesis: Relevance to the lipodystrophy phenotype in Marfan syndrome and related conditions. AB - Fibrillin-1 is a large glycoprotein encoded by the FBN1 gene in humans. It provides strength and elasticity to connective tissues and is involved in regulating the bioavailability of the growth factor TGFbeta. Mutations in FBN1 may be associated with depleted or abnormal adipose tissue, seen in some patients with Marfan syndrome and lipodystrophies. As this lack of adipose tissue does not result in high morbidity or mortality, it is generally under-appreciated, but is a cause of psychosocial problems particularly to young patients. We examined the role of fibrillin-1 in adipogenesis. In inbred mouse strains we found significant variation in the level of expression in the Fbn1 gene that correlated with variation in several measures of body fat, suggesting that mouse fibrillin-1 is associated with the level of fat tissue. Furthermore, we found that FBN1 mRNA was up-regulated in the adipose tissue of obese women compared to non-obese, and associated with an increase in adipocyte size. We used human mesenchymal stem cells differentiated in culture to adipocytes to show that fibrillin-1 declines after the initiation of differentiation. Gene expression results from a similar experiment (available through the FANTOM5 project) revealed that the decline in fibrillin-1 protein was paralleled by a decline in FBN1 mRNA. Examination of the FBN1 gene showed that the region commonly affected in FBN1-associated lipodystrophy is highly conserved both across the three human fibrillin genes and across genes encoding fibrillin-1 in vertebrates. These results suggest that fibrillin-1 is involved as the undifferentiated mesenchymal stem cells transition to adipogenesis but then declines as the developing adipocytes take on their final phenotype. Since the C-terminal peptide of fibrillin-1 is a glucogenic hormone, individuals with low fibrillin-1 (for example with FBN1 mutations associated with lipodystrophy) may fail to differentiate adipocytes and/or to accumulate adipocyte lipids, although this still needs to be shown experimentally. PMID- 27386758 TI - The International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC): 2010-2015. AB - BACKGROUND: Central and East European (CEE) patients with acute coronary syndromes (ACS) have worse outcomes than US and West European patients, including higher mortality rates. The aim of the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC) was to define patient and treatment characteristics in order to examine whether differences in clinical and ethnic factors or healthcare organization may mediate the observed disparities in outcomes. METHODS AND RESULTS: Between October 2010 and December 2015, 14,326 patients with ACS were prospectively enrolled. Of these patients 8650 (60%) had ST-segment elevation myocardial infarction (STEMI). Patients were enrolled from 41 centers in 12 countries in Europe. Standardized electronic case report forms were completed by trained study coordinators, and included fields relating to demographic factors, medical history and processes of inpatient care, supplemented with a detailed baseline interview on time delays to hospital admission. Blood sampling for genetic data were obtained at hospital discharge. Prospective individual patient follow-up was carried out with a focus on patient health (symptoms) and vital status. Thirty day follow-up was 100% complete. Difficulties were found for recruitment of patients at 6months. Publications are available at ClinicalTrials.gov: NCT01218776. CONCLUSIONS: ISACS-TC is a novel ACS registry with detailed information on CEE patients' clinical, demographic, treatment, and metabolic characteristics and health status. The concurrent enrollment of patients from some European Union founding members provides greater generalizability of the data. ISACS-TC may help to make an additional improvement in clinical outcomes of countries with economy in transition. PMID- 27386759 TI - Retraction Notice to: Can be galectin-3 a novel marker in determining mortality in hemodialysis patients? PMID- 27386762 TI - Trauma and pregnancy: What anesthesiologist should know. PMID- 27386761 TI - Zero-valent Fe confined mesoporous silica nanocarriers (Fe(0) @ MCM-41) for targeting experimental orthotopic glioma in rats. AB - Mesoporous silica nanoparticles (MSNs) impregnated with zero-valent Fe (Fe(0) @ MCM-41) represent an attractive nanocarrier system for drug delivery into tumor cells. The major goal of this work was to assess whether MSNs can penetrate the blood-brain barrier in a glioblastoma rat model. Synthesized MSNs nanomaterials were characterized by energy dispersive X-ray spectroscopy, measurements of X-ray diffraction, scanning electron microscopy and Mossbauer spectroscopy. For the detection of the MSNs by MR and for biodistribution studies MSNs were labeled with zero-valent Fe. Subsequent magnetometry and nonlinear-longitudinal-response M2 (NLR-M2) measurements confirmed the MR negative contrast enhancement properties of the nanoparticles. After incubation of different tumor (C6 glioma, U87 glioma, K562 erythroleukemia, HeLa cervix carcinoma) and normal cells such as fibroblasts and peripheral blood mononuclear cells (PBMCs) MSNs rapidly get internalized into the cytosol. Intracellular residing MSNs result in an enhanced cytotoxicity as Fe(0) @ MCM-41 promote the reactive oxygen species production. MRI and histological studies indicated an accumulation of intravenously injected Fe(0) @ MCM-41 MSNs in orthotopic C6 glioma model. Biodistribution studies with measurements of second harmonic of magnetization demonstrated an increased and dose-dependent retention of MSNs in tumor tissues. Taken together, this study demonstrates that MSNs can enter the blood-brain barrier and accumulate in tumorous tissues. PMID- 27386763 TI - Intensive care and pregnancy: Epidemiology and general principles of management of obstetrics ICU patients during pregnancy. AB - In developed countries, the rate of obstetric ICU admissions (admission during pregnancy or the postpartum period) is between 0.5 and 4 per 1000 deliveries and the overall case-fatality rate is about 2%. The most two common causes of obstetric ICU admissions concerned direct obstetric pathologies: obstetric hemorrhage and hypertensive disorders of pregnancy. This review summarized the principles of management of critically ill pregnant patient. Its imply taking care of two patients in the same time. A coordinated multidisciplinary team including intensivists, anesthesiologists, obstetricians, pediatricians and pharmacists is therefore necessary. This team must work effectively together with regular staff aiming to evaluate daily the need to maintain the patient in intensive care unit or to prompt delivery. Keeping mother and baby together and fetal well-being must be balanced with the need of specialized advanced life support for the mother. The maternal physiological changes imply various consequences on management. The uterus aorto-caval compression implies tilting left the parturient. In case of cardiac arrest, uterus displacement and urgent cesarean delivery are needed. The high risk of aspiration and difficult tracheal intubation must be anticipated. Even during acute respiratory distress syndrome, hypoxemia and permissive hypercapnia must be avoided due to their negative impact on the fetus. Careful analysis of the benefit-risk ratio is needed before all drug administration. Streptococcal toxic shock syndrome and perineal fasciitis must be feared and a high level of suspicion of sepsis must be maintained. Finally the potential benefits of an ultrasound-based management are detailed. PMID- 27386764 TI - Fever and pregnancy. AB - Severe infections during pregnancy and postpartum are rare, despite a high frequency of bacteraemia, but remain on of the leading cause of maternal death. Therapeutic guidelines validated in general population should be applied to pregnant women, with regards to their specificities: insidious clinical signs and rapid onset, clinical presentation often as respiratory failure due to physiological changes during pregnancy; most frequent causes: pneumonia, pyelonephritis, genitary tract infections; sensibility to virus, Listeria, malaria, due to immunological changes during pregnancy; caesarean section is the single most important risk factor of postpartum infection; aggressive treatment should be started promptly, including fluid infusion and early administration of vasoactive agents (Norepinephrine); broad-spectrum intravenous empirical antibiotic therapy must be established immediately (within the first hour), and chosen according to frequent microorganisms involved in sepsis during pregnancy; infectious source, mostly pelvic, is often accessible to surgery; if foetal extraction does not improve maternal outcomes, it remains necessary for obstetrical or foetal reasons and mandatory if chorioamnionitis is confirmed; specific attention should be drawn to streptococcus A invasive infection which experiments a recent resurgence and is correlated to a high morbidity and mortality for both the mother and the foetus; protocols should be written in every maternity. PMID- 27386765 TI - Triggering and modulation of the host-parasite interplay by Echinococcus multilocularis: a review - CORRIGENDUM. PMID- 27386767 TI - True or False: Prognosis Is Excellent for Sudden Cardiac Death Survivors Due to Variant Angina. PMID- 27386768 TI - End of the Road for Vagus Nerve Stimulation? PMID- 27386766 TI - Prognosis of Variant Angina Manifesting as Aborted Sudden Cardiac Death. AB - BACKGROUND: The long-term prognosis of patients with variant angina presenting with aborted sudden cardiac death (ASCD) is unknown. OBJECTIVES: The purpose of this study was to evaluate the long-term mortality and ventricular tachyarrhythmic events of variant angina with and without ASCD. METHODS: Between March 1996 and September 2014, 188 patients with variant angina with ASCD and 1,844 patients with variant angina without ASCD were retrospectively enrolled from 13 heart centers in South Korea. The primary endpoint was cardiac death. RESULTS: Predictors of ASCD manifestation included age (odd ratio [OR]: 0.980 by 1 year increase; 95% confidence interval [CI]: 0.96 to 1.00; p = 0.013), hypertension (OR: 0.51; 95% CI: 0.37 to 0.70; p < 0.001), hyperlipidemia (OR: 0.38; 95% CI: 0.25 to 0.58; p < 0.001), family history of sudden cardiac death (OR: 3.67; 95% CI: 1.27 to 10.6; p = 0.016), multivessel spasm (OR: 2.06; 95% CI: 1.33 to 3.19; p = 0.001), and left anterior descending artery spasm (OR: 1.40; 95% CI: 1.02 to 1.92; p = 0.04). Over a median follow-up of 7.5 years, the incidence of cardiac death was significantly higher in ASCD patients (24.1 per 1,000 patient-years vs. 2.7 per 1,000 patient-years; adjusted hazard ratio [HR]: 7.26; 95% CI: 4.21 to 12.5; p < 0.001). Death from any cause also occurred more frequently in ASCD patients (27.5 per 1,000 patient-years vs. 9.6 per 1,000 patient-years; adjusted HR: 3.00; 95% CI: 1.92 to 4.67; p < 0.001). The incidence rate of recurrent ventricular tachyarrhythmia in ASCD patients was 32.4 per 1,000 patient-years, and the composite of cardiac death and ventricular tachyarrhythmia was 44.9 per 1,000 patient-years. A total of 24 ASCD patients received implantable cardioverter-defibrillators (ICDs). There was a nonsignificant trend of a lower rate of cardiac death in patients with ICDs than those without ICDs (p = 0.15). CONCLUSIONS: The prognosis of patients with variant angina with ASCD was worse than other patients with variant angina. In addition, our findings supported ICDs in these high-risk patients as a secondary prevention because current multiple vasodilator therapy appeared to be less optimal. PMID- 27386770 TI - Transthyretin Amyloidosis: A "Zebra" of Many Stripes. PMID- 27386769 TI - Genotype and Phenotype of Transthyretin Cardiac Amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). AB - BACKGROUND: Transthyretin amyloidosis (ATTR) is a heterogeneous disorder with multiorgan involvement and a genetic or nongenetic basis. OBJECTIVES: The goal of this study was to describe ATTR in the United States by using data from the THAOS (Transthyretin Amyloidosis Outcomes Survey) registry. METHODS: Demographic, clinical, and genetic features of patients enrolled in the THAOS registry in the United States (n = 390) were compared with data from patients from other regions of the world (ROW) (n = 2,140). The focus was on the phenotypic expression and survival in the majority of U.S. subjects with valine-to-isoleucine substitution at position 122 (Val122Ile) (n = 91) and wild-type ATTR (n = 189). RESULTS: U.S. subjects are older (70 vs. 46 years), more often male (85.4% vs. 50.6%), and more often of African descent (25.4% vs. 0.5%) than the ROW. A significantly higher percentage of U.S. patients with ATTR amyloid seen at cardiology sites had wild type disease than the ROW (50.5% vs. 26.2%). In the United States, 34 different mutations (n = 201) have been reported, with the most common being Val122Ile (n = 91; 45.3%) and Thr60Ala (n = 41; 20.4%). Overall, 91 (85%) of 107 patients with Val122Ile were from the United States, where Val122Ile subjects were younger and more often female and black than patients with wild-type disease, and had similar cardiac phenotype but a greater burden of neurologic symptoms (pain, numbness, tingling, and walking disability) and worse quality of life. Advancing age and lower mean arterial pressure, but not the presence of a transthyretin mutation, were independently associated with higher mortality from a multivariate analysis of survival. CONCLUSIONS: In the THAOS registry, ATTR in the United States is overwhelmingly a disorder of older adult male subjects with a cardiac-predominant phenotype. Val122Ile is the most common transthyretin mutation, and neurologic phenotypic expression differs between wild-type disease and Val122Ile, but survival from enrollment in THAOS does not. (Transthyretin-Associated Amyloidoses Outcome Survey [THAOS]; NCT00628745). PMID- 27386771 TI - Dissection and Aneurysm in Patients With Fibromuscular Dysplasia: Findings From the U.S. Registry for FMD. AB - BACKGROUND: Fibromuscular dysplasia (FMD) is a noninflammatory arterial disease that predominantly affects women. The arterial manifestations may include beading, stenosis, aneurysm, dissection, or tortuosity. OBJECTIVES: This study compared the frequency, location, and outcomes of FMD patients with aneurysm and/or dissection to those of patients without. METHODS: The U.S. Registry for FMD involves 12 clinical centers. This analysis included clinical history, diagnostic, and therapeutic procedure results for 921 FMD patients enrolled in the registry as of October 17, 2014. RESULTS: Aneurysm occurred in 200 patients (21.7%) and dissection in 237 patients (25.7%); in total, 384 patients (41.7%) had an aneurysm and/or a dissection by the time of FMD diagnosis. The extracranial carotid, renal, and intracranial arteries were the most common sites of aneurysm; dissection most often occurred in the extracranial carotid, vertebral, renal, and coronary arteries. FMD patients with dissection were younger at presentation (48.4 vs. 53.5 years of age, respectively; p < 0.0001) and experienced more neurological symptoms and other end-organ ischemic events than those without dissection. One-third of aneurysm patients (63 of 200) underwent therapeutic intervention for aneurysm repair. CONCLUSIONS: Patients with FMD have a high prevalence of aneurysm and/or dissection prior to or at the time of FMD diagnosis. Patients with dissection were more likely to experience ischemic events, and a significant number of patients with dissection or aneurysm underwent therapeutic procedures for these vascular events. Because of the high prevalence and associated morbidity in patients with FMD who have an aneurysm and/or dissection, it is recommended that every patient with FMD undergo one-time cross-sectional imaging from head to pelvis with computed tomographic angiography or magnetic resonance angiography. PMID- 27386772 TI - People Have the Power: Fibromuscular Dysplasia Complications. PMID- 27386773 TI - Functional Status, Pulmonary Artery Pressure, and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction. AB - BACKGROUND: Patients with heart failure with preserved ejection fraction have functional impairment resulting in reduced quality of life. Specific pathological mechanisms underlying symptoms have not yet been defined. OBJECTIVES: The aim of this study was to identify hemodynamic and other patient-related variables that are associated with New York Heart Association (NYHA) functional class and to analyze functional class in perspective with other clinical, laboratory, imaging, and hemodynamic parameters with respect to its influence on outcomes. METHODS: Between January 2011 and February 2015, 193 patients with confirmed heart failure with preserved ejection fraction were enrolled. RESULTS: Those in more advanced NYHA functional classes (III and IV; n = 136) were older (p = 0.008), had higher body mass indexes (p = 0.004), and had higher levels of N-terminal pro-brain natriuretic peptide (p = 0.001) compared with less symptomatic patients (NYHA class II; n = 57). Furthermore, parameters reflecting left ventricular diastolic dysfunction were more pronounced in advanced NYHA classes (early mitral inflow velocity/early diastolic mitral annular velocity; p = 0.023) as well as parameters reflecting right ventricular afterload (diastolic pulmonary artery pressure; p < 0.001). By multivariate regression analysis, age (p = 0.007), body mass index (p = 0.002), N-terminal pro-brain natriuretic peptide (p < 0.001), early mitral inflow velocity/mitral peak velocity of late filling (p = 0.031), and diastolic pulmonary artery pressure (p < 0.001) were independently associated with advanced NYHA class. After 21.9 months of follow-up, 64 patients (33.2%) reached the combined endpoint, defined as hospitalization for heart failure and/or cardiac death. By multivariate Cox analysis, NYHA functional class was independently associated with outcome (hazard ratio: 2.133; p = 0.040), as well as N-terminal pro-brain natriuretic peptide (hazard ratio: 1.655; p < 0.001) and impaired right ventricular function (hazard ratio: 2.360; p = 0.001). CONCLUSIONS: Symptoms of breathlessness in patients with heart failure with preserved ejection fraction are multifactorial and largely related to body mass index, left ventricular diastolic function, and the pulmonary vasculature. Clinically meaningful therapeutic interventions should target body weight, left ventricular stiffness, and concomitant pulmonary vascular disease. PMID- 27386774 TI - The HFpEF Obesity Phenotype: The Elephant in the Room. PMID- 27386776 TI - A Baby in the Bathwater: Preserving Evidence-Based Medicine. PMID- 27386775 TI - Achievements and Limitations of Evidence-Based Medicine. AB - Evidence-based medicine (EBM) has a long history, but was revived in the early 1990s by a campaign mounted by a movement that took its name. The EBM movement focused attention on the need for greater objectivity in medical decision-making and led to the Cochrane Collaboration, which provides reviews of evidence on the basis of comparative research. Important limitations of EBM's effect on medicine have also emerged. Failure to acknowledge the limitations of clinical trials and systematic reviews has limited their applicability to individual patients' circumstances. An almost exclusive focus on drugs and devices has left vast areas of health care in an evidence vacuum. An overdependence on commissions for its research may have limited its independence in selecting what it investigates. EBM needs to widen its scope beyond drugs and devices to address many areas that often lack evidence at present, notably, health policy, management, and reforms. PMID- 27386777 TI - Management of Periprocedural Anticoagulation: A Survey of Contemporary Practice. AB - Interruption of oral anticoagulation (AC) for surgery or an invasive procedure is a complicated process. Practice guidelines provide only general recommendations, and care of such patients occurs across multiple specialties. The availability of direct oral anticoagulants further complicates decision making and guidance here is limited. To evaluate current practice patterns in the United States for bridging AC, a survey was developed by the American College of Cardiology Anticoagulation Work Group. The goal of the survey was to assess how general and subspecialty cardiologists, internists, gastroenterologists, and orthopedic surgeons currently manage patients who receive AC and undergo surgery or an invasive procedure. The survey was completed by 945 physicians involved in the periprocedural management of AC. The results provide a template for educational and research projects geared toward the development of clinical pathways and point-of-care tools to improve this area of health care. PMID- 27386778 TI - Reading the Tea Leaves: Where Will Cardiology Be in 2050? PMID- 27386779 TI - Demystifying the New Statistical Recommendations: The Use and Reporting of p Values. PMID- 27386780 TI - Statin-Induced Anti-HMGCR-Associated Myopathy. PMID- 27386781 TI - Effects of Prasugrel Versus Clopidogrel on Coronary Microvascular Function in Patients Undergoing Elective PCI. PMID- 27386782 TI - Peripheral Artery Disease and Atrial Fibrillation: The Dangerous Combination. PMID- 27386783 TI - Reply: Peripheral Artery Disease and Atrial Fibrillation: The Dangerous Combination. PMID- 27386784 TI - Post-TAVR Valve Hemodynamic Deterioration. PMID- 27386785 TI - Maximizing the spatial representativeness of NO2 monitoring data using a combination of local wind-based sectoral division and seasonal and diurnal correction factors. AB - This article describes a new methodology for increasing the spatial representativeness of individual monitoring sites. Air pollution levels at a given point are influenced by emission sources in the immediate vicinity. Since emission sources are rarely uniformly distributed around a site, concentration levels will inevitably be most affected by the sources in the prevailing upwind direction. The methodology provides a means of capturing this effect and providing additional information regarding source/pollution relationships. The methodology allows for the division of the air quality data from a given monitoring site into a number of sectors or wedges based on wind direction and estimation of annual mean values for each sector, thus optimising the information that can be obtained from a single monitoring station. The method corrects for short-term data, diurnal and seasonal variations in concentrations (which can produce uneven weighting of data within each sector) and uneven frequency of wind directions. Significant improvements in correlations between the air quality data and the spatial air quality indicators were obtained after application of the correction factors. This suggests the application of these techniques would be of significant benefit in land-use regression modelling studies. Furthermore, the method was found to be very useful for estimating long-term mean values and wind direction sector values using only short-term monitoring data. The methods presented in this article can result in cost savings through minimising the number of monitoring sites required for air quality studies while also capturing a greater degree of variability in spatial characteristics. In this way, more reliable, but also more expensive monitoring techniques can be used in preference to a higher number of low-cost but less reliable techniques. The methods described in this article have applications in local air quality management, source receptor analysis, land-use regression mapping and modelling and population exposure studies. PMID- 27386787 TI - Microstructured Hydrogel Templates for the Formation of Conductive Gold Nanowire Arrays. AB - Microstructured hydrogel allows for a new template-guided method to obtain conductive nanowire arrays on a large scale. To generate the template, an imprinting process is used in order to synthesize the hydrogel directly into the grooves of wrinkled polydimethylsiloxane (PDMS). The resulting poly(N vinylimidazole)-based hydrogel is defined by the PDMS stamp in pattern and size. Subsequently, tetrachloroaurate(III) ions from aqueous solution are coordinated within the humps of the N-vinylimidazole-containing polymer template and reduced by air plasma. After reduction and development of the gold, to achieve conductive wires, the extension perpendicular to the long axis (width) of the gold strings is considerably reduced compared to the dimension of the parental hydrogel wrinkles (from ~1 MUm down to 200-300 nm). At the same time, the wire-to-wire distance and the overall length of the wires is preserved. The PDMS templates and hydrogel structures are analyzed with scanning force microscopy (SFM) and the gold structures via scanning electron microscopy (SEM) and energy-dispersive X ray spectroscopy. The conductivity measurements of the gold nanowires are performed in situ in the SEM, showing highly conductive gold leads. Hence, this method can be regarded as a facile nonlithographic top-down approach from micrometer-sized structures to nanometer-sized features. PMID- 27386786 TI - Feasibility of interim positron emission tomography (PET)-adapted therapy in HIV positive patients with advanced Hodgkin lymphoma (HL): a sub-analysis of SWOG S0816 Phase 2 trial. PMID- 27386788 TI - Stevens-Johnson Syndrome and Corneal Ectasia: Management and a Case for Association. AB - PURPOSE: To report the occurrence of corneal ectasia (ECT) in patients with history of Stevens-Johnson syndrome (SJS), and to make the case for an association between these 2 diagnoses. We also report the impact of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment on visual acuity (VA) in these patients. DESIGN: Retrospective cohort study. METHODS: A manufacturing database of PROSE patients from 2002 to 2014 at Boston Foundation for Sight (BFS), a single-center clinical practice, was reviewed to identify patients with diagnoses of both SJS and ECT. RESULTS: Nine patients were identified with diagnoses of both SJS and ECT. In each case, review of the medical record revealed that diagnosis of SJS preceded that of ECT. The prevalence of ECT in this population exceeded that in the general population (P < .0001). Videokeratography was available for 13 eyes in 7 patients; using Krumeich's classification of keratoconus, 3 eyes were found to be at stage 1, 3 at stage 2, 1 at stage 3, and 6 at stage 4. Sixteen of 18 eyes underwent PROSE treatment. Of these 16 eyes, initial median VA was 20/200 (range, count fingers to 20/20; logMAR 1.0). Median VA after PROSE customization was 20/30 (range, 20/60-20/15; logMAR 0.1761, P < .0025). CONCLUSIONS: ECT occurs at a higher-than expected rate in patients with a history of SJS. PROSE treatment improves VA in these patients. The basis of the association between SJS and ECT is considered, as well as the role of plausible contributory factors such as corneal microtrauma and matrix metalloproteinases. PMID- 27386789 TI - Potential applications of metagenomics to assess the biological effects of food structure and function. AB - Metagenomics, or the collective study of genomes is an important emerging area in microbiology and related fields, and is increasingly being recognized as a tool to characterize the microbial community structure and function of diverse sample types. Metagenomics compares sequences to existing databases to enable the identification of potential microbial reservoirs and predict specific functions; yet, metagenomics has not been widely applied to understand how changes in the food structure and composition affect microbial communities and their function in the human gut. Studies are needed to understand the digestion of food products, and to measure their effectiveness in preserving a healthy microbiome, as well as intestinal function. We suggest the use of metagenomics with validation techniques such as Polymerase Chain Reaction (PCR), cloning and functional assays to assess the biological effects of food structure and function. PMID- 27386791 TI - New aspects of developing a dry powder inhalation formulation applying the quality-by-design approach. AB - The current work outlines the application of an up-to-date and regulatory-based pharmaceutical quality management method, applied as a new development concept in the process of formulating dry powder inhalation systems (DPIs). According to the Quality by Design (QbD) methodology and Risk Assessment (RA) thinking, a mannitol based co-spray dried formula was produced as a model dosage form with meloxicam as the model active agent. The concept and the elements of the QbD approach (regarding its systemic, scientific, risk-based, holistic, and proactive nature with defined steps for pharmaceutical development), as well as the experimental drug formulation (including the technological parameters assessed and the methods and processes applied) are described in the current paper. Findings of the QbD based theoretical prediction and the results of the experimental development are compared and presented. Characteristics of the developed end-product were in correlation with the predictions, and all data were confirmed by the relevant results of the in vitro investigations. These results support the importance of using the QbD approach in new drug formulation, and prove its good usability in the early development process of DPIs. This innovative formulation technology and product appear to have a great potential in pulmonary drug delivery. PMID- 27386790 TI - Morphologically and Functionally Distinct Lipid Droplet Subpopulations. AB - Lipid droplet (LD), a multi-functional organelle, is often found to associate with other cellular membranous structures and vary in size in a given cell, which may be related to their functional diversity. Here we established a method to separate LD subpopulations from isolated CHO K2 LDs into three different size categories. The subpopulation with smallest LDs was nearly free of ER and other membranous structures while those with larger LDs contained intact ER. These distinct subpopulations of LDs differed in their protein composition and ability to recruit proteins. This method was also applicable to LDs obtained from other sources, such as Huh7 cells, mouse liver and brown adipose tissue, et al. We developed an in vitro assay requiring only isolated LDs, Coenzyme A, and ATP to drive lipid synthesis. The LD subpopulation nearly depleted of ER was able to incorporate fatty acids into triacylglycerol and phospholipids. Together, our data demonstrate that LDs in a given cell are heterogeneous in size and function, and suggest that LDs are one of cellular lipid synthetic organelles. PMID- 27386792 TI - Development of nanoemulsions for topical delivery of vitamin K1. AB - Vitamin K1 (VK1) is a natural and lipophilic compound currently used in dermatological formulations. In this work, nanoemulsions containing VK1 have been proposed to overcome some issues associated to semisolid VK1-incorporating formulations. The study has been focused on the design of a lipid-free aqueous formulation, easy to prepare and with low cost of production. Thus, a simply protocol, using a low-energy method, has been used to spontaneously form the nanoemulsions. The nanoemulsion composition has been optimized to improve its physical stability during storage in different conditions. Then, the possibility to administer VK1-containing nanoemulsions by nebulization without significant alteration of the formulation was tested. Moreover, the VK1 accumulation into the skin layers have been evaluated through permeation experiments on Franz cells, ATR-FITR analysis, confocal laser scanning microscopy (CLSM) observations, and high performance liquid chromatography (HPLC) analysis. The study demonstrated that NEs represent an interesting option for the commercial development of an aqueous spray formulation for the topical delivery of VK1. PMID- 27386794 TI - Effectiveness of the Ponseti method for treating clubfoot associated with myelomeningocele: 3-9 years follow-up. AB - Clubfoot in myelomeningocele patients is characterized by its stiffness, severe rigidity and has traditionally been treated with extensive soft-tissue release surgery with poor outcomes. We present our experience using the Ponseti method to treat clubfoot associated with myelomeningocele. This was a retrospective, consecutive review over a 10-year period in our tertiary centre. On initial presentation, patients were assessed using the Pirani scoring system and the standard Ponseti method was initiated. Our outcome measures were successful functional correction of deformity defined as achieving a plantigrade pain-free foot. Secondary outcome measures included relapse and the need for surgical procedures. A total of 11 children with 18 myelomeningocele-associated clubfeet were included, with an average follow-up duration of 4.5 years (range 3-9 years). The average age at presentation was 4.7 weeks, with an average Pirani score of 5.5. Initial correction was achieved in all children with an average of 7 (range 4-9) Ponseti casts and tendo-achilles tenotomy was performed in 17 of 18 feet (94.4%). Nine children with 15 of 18 (83.3%) myelomeningocele-associated clubfeet achieved a satisfactory outcome at the final follow-up, with functional, pain free feet. Recurrence occurred in five of 15 (33.3%) feet, which was managed successfully with a second tendo-achilles tenotomy and further Ponseti casting. Two children three of 18 (16.7%) failed Ponseti treatment. Ponseti method is an effective first-line treatment for myelomeningocele-associated clubfoot to achieve functional painless feet; children will often require more casts and have a higher risk of relapse. PMID- 27386793 TI - A global test for gene-gene interactions based on random matrix theory. AB - Statistical interactions between markers of genetic variation, or gene-gene interactions, are believed to play an important role in the etiology of many multifactorial diseases and other complex phenotypes. Unfortunately, detecting gene-gene interactions is extremely challenging due to the large number of potential interactions and ambiguity regarding marker coding and interaction scale. For many data sets, there is insufficient statistical power to evaluate all candidate gene-gene interactions. In these cases, a global test for gene-gene interactions may be the best option. Global tests have much greater power relative to multiple individual interaction tests and can be used on subsets of the markers as an initial filter prior to testing for specific interactions. In this paper, we describe a novel global test for gene-gene interactions, the global epistasis test (GET), that is based on results from random matrix theory. As we show via simulation studies based on previously proposed models for common diseases including rheumatoid arthritis, type 2 diabetes, and breast cancer, our proposed GET method has superior performance characteristics relative to existing global gene-gene interaction tests. A glaucoma GWAS data set is used to demonstrate the practical utility of the GET method. PMID- 27386795 TI - Authors' reply: Escherichia coli harbouring mcr-1 gene isolated from poultry not exposed to polymyxins in Brazil. PMID- 27386796 TI - Immediate response to prasugrel loading in patients with ST-elevation myocardial infarction: Predictors and outcome. AB - INTRODUCTION: Information regarding immediate response to novel P2Y12 inhibitors in ST-elevation myocardial infarction (STEMI) is scarce and has been associated with adequate reperfusion. Recent studies have shown that the onset of anti platelet effects of novel P2Y12 inhibitors in patients with STEMI might be slower and more variable than in stable coronary syndrome. We aimed to assess the predictors and significance of immediate platelet response to prasugrel loading in STEMI. METHODS: Platelet aggregation (PA) was prospectively evaluated in STEMI patients upon prasugrel loading and at primary percutaneous coronary intervention (PPCI). Early platelet responsiveness was defined as percent reduction of PA from baseline to PPCI, divided by the time lapse from loading to PPCI. High- and low platelet responsiveness was defined as above and below the median value respectively. RESULTS: Fifty consecutive STEMI patients (age 58+/-8, 90% male) underwent PPCI with a mean door-to-balloon time of 42+/-15min. Mean PA upon prasugrel loading and at PPCI was 76+/-9% and 63+/-19%, respectively. Older age and prior aspirin use were predictors of low platelet responsiveness to prasugrel [beta=(-0.33), p=0.02 and beta=(-0.28), p=0.04, respectively]. Fast compared with slow responders demonstrated more frequent early ST resolution (93% vs. 72%, p=0.02) and lower peak troponin levels (76+/-62MUg/L vs. 48+/-28MUg/L, p=0.05). CONCLUSIONS: Immediate platelet responsiveness to prasugrel among STEMI patients is highly variable and inversely associated with older age and prior aspirin use. Fast compared with slow responders have improved reperfusion and infarct size markers. PMID- 27386797 TI - Acoustic-Phonetic Versus Lexical Processing in Nonnative Listeners Differing in Their Dominant Language. AB - PURPOSE: Nonnative listeners have difficulty recognizing English words due to underdeveloped acoustic-phonetic and/or lexical skills. The present study used Boothroyd and Nittrouer's (1988)j factor to tease apart these two components of word recognition. METHOD: Participants included 15 native English and 29 native Russian listeners. Fourteen and 15 of the Russian listeners reported English (ED) and Russian (RD) to be their dominant language, respectively. Listeners were presented 119 consonant-vowel-consonant real and nonsense words in speech spectrum noise at +6 dB SNR. Responses were scored for word and phoneme recognition, the logarithmic quotient of which yielded j. RESULTS: Word and phoneme recognition was comparable between native and ED listeners but poorer in RD listeners. Analysis of j indicated less effective use of lexical information in RD than in native and ED listeners. Lexical processing was strongly correlated with the length of residence in the United States. CONCLUSIONS: Language background is important for nonnative word recognition. Lexical skills can be regarded as nativelike in ED nonnative listeners. Compromised word recognition in ED listeners is unlikely a result of poor lexical processing. Performance should be interpreted with caution for listeners dominant in their first language, whose word recognition is affected by both lexical and acoustic-phonetic factors. PMID- 27386798 TI - Hepatic myelolipoma in two Goeldi's monkeys from South America held captive. AB - Two cases of hepatic myelolipoma in Goeldi's monkeys from South America are described. One was a female evaluated due progressive abdominal distension. Ultrasound and computed tomography detected hepatic mass. Partial hepatectomy was performed, but the monkey died after surgery. Case 2 was a male that died suddenly, showing non-specific clinical signs. PMID- 27386800 TI - Cobalt phosphide nanowires: an efficient electrocatalyst for enzymeless hydrogen peroxide detection. AB - In this letter, we demonstrate for the first time that cobalt phosphide nanowires (CoP NWs) exhibit remarkable catalytic activity toward electrochemical detection of hydrogen peroxide (H2O2). As an enzymeless H2O2 sensor, such CoP NWs show a fast amperometric response within 5 s and a low detection limit of 0.48 MUM. In addition, this nonenzymatic sensor displays good selectivity, long-term stability and excellent reproducibility. PMID- 27386801 TI - What's New for Tranexamic Acid? PMID- 27386799 TI - Human induced pluripotent stem cell-derived hepatic cell lines as a new model for host interaction with hepatitis B virus. AB - Hepatitis B virus (HBV) is not eradicated by current antiviral therapies due to persistence of HBV covalently closed circular DNA (cccDNA) in host cells, and thus development of novel culture models for productive HBV infection is urgently needed, which will allow the study of HBV cccDNA eradication. To meet this need, we developed culture models of HBV infection using human induced pluripotent stem cell-derived hepatocyte lineages, including immature proliferating hepatic progenitor-like cell lines (iPS-HPCs) and differentiated hepatocyte-like cells (iPS-Heps). These cells were susceptible to HBV infection, produced HBV particles, and maintained innate immune responses. The infection efficiency of HBV in iPS-HPCs predominantly depended on the expression levels of sodium taurocholate cotransporting polypeptide (NTCP), and was low relative to iPS-Heps: however, long-term culture of iPS-Heps was difficult. To provide a model for HBV persistence, iPS-HPCs overexpressing NTCP were established. The long-term persistence of HBV cccDNA was detected in iPS-HPCs overexpressing NTCP, and depended on the inhibition of the Janus-kinase signaling pathway. In conclusion, this study provides evidence that iPS-derived hepatic cell lines can be utilized for novel HBV culture models with genetic variation to investigate the interactions between HBV and host cells and the development of anti-HBV strategies. PMID- 27386802 TI - High-Efficiency Nonfullerene Polymer Solar Cells with Medium Bandgap Polymer Donor and Narrow Bandgap Organic Semiconductor Acceptor. AB - A nonfullerene polymer solar cell with a high efficiency of 9.26% is realized by using benzodithiophene-alt-fluorobenzotriazole copolymer J51 as a medium-bandgap polymer donor and the low-bandgap organic semiconductor ITIC with high extinction coefficients as the acceptor. PMID- 27386803 TI - Development of minimally invasive surgery for sinonasal malignancy. AB - Sinonasal malignancies are rare and histologically heterogeneous. Treatment is complicated by tumor aggressiveness and location near critical anatomic structures (orbita, skull base, etc.). This low incidence and histologic diversity make prospective studies unfeasible, and thus therapeutic guidelines difficult to establish. The gold standard for surgery is a transfacial approach, with craniofacial resection in case of skull-base involvement. However, these techniques are associated with non-negligible perioperative morbidity. In the past two decades, endoscopic surgery has made major progress, extending its indications: initially developed for functional sinus surgery, it is now applied in benign skull-base pathologies (CSF leakage, meningocele, etc.) and, more recently, in sinonasal malignancy. Literature analysis shows a significant decrease in morbidity and improved quality of life associated with endoscopic endonasal surgery, with oncologic safety and efficacy in well-selected cases, although dependent on operator experience. Additional studies with longer follow up and comparison between histologic subtypes will be needed. PMID- 27386804 TI - Hand Robotic Therapy in Children with Hemiparesis: A Pilot Study. AB - OBJECTIVE: The aim of this study was to understand the impact of training with a hand robotic device on hand paresis and function in a population of children with hemiparesis. METHODS: Twelve children with hemiparesis (mean age, 9 [SD, 3.64] years) completed participation in this prospective, experimental, pilot study. Participants underwent clinical assessments at baseline and again 6 weeks later with instructions to not initiate new therapies. After these assessments, participants received 6 weeks of training with a hand robotic device, consisting of 1-hour sessions, 3 times weekly. Assessments were repeated on completion of training. RESULTS: Results showed significant improvements after training on the Assisting Hand Assessment (mean difference, 2.0 Assisting Hand Assessment units; P = 0.011) and on the upper-extremity component of the Fugl-Meyer scale (raw score mean difference, 4.334; P = 0.001). No significant improvements between pretest and posttest were noted on the Jebsen-Taylor Test of Hand Function, the Quality of Upper Extremity Skills Test, or the Pediatric Evaluation of Disability Inventory after intervention. Total active mobility of digits and grip strength also failed to demonstrate significant changes after training. INTERPRETATION: Participants tolerated training with the hand robotic device, and significant improvements in bimanual hand use, as well as impairment-based scales, were noted. Improvements were carried over into bimanual skills during play. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Understand key components of neuroplasticity; (2) Discuss the benefits of robotic therapy in the recovery of hand function in pediatric patients with hemiplegia; and (3) Appropriately incorporate robotic therapy into the treatment plan of pediatric patients with hemiplegia. LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity. PMID- 27386805 TI - The Impact of the Immediate Postoperative Prosthesis on Patient Mobility and Quality of Life after Transtibial Amputation. AB - BACKGROUND: The immediate postoperative prosthesis has been purported to allow early mobilization with potential physical and psychologic benefits to patients. This study used accelerometers and validated questionnaires to prospectively examine activity level and quality of life data for patients receiving an immediate postoperative prosthesis after transtibial amputation. METHODS: A total of 10 patients were included in the study. Mean age was 58 yrs (range, 22-69 yrs), there were 9 men and 1 woman, and reason for amputation was nonhealing gangrenous ulcer in 9 patients and ischemic limb in 1 patient. Patients were followed for 6 wks. Activity data were collected on ActiGraph GT3X accelerometers and analyzed using ActiLife 6 Data Analysis Software. At the 6-wk postoperative visit, an Amputee Mobility Predictor clinician-rated performance evaluation was conducted and a Short Form-36 questionnaire was completed. RESULTS: Patients in the cohort spent an average of 88% (range, 83%-92%) of their time sedentary, 11.5% (range, 7.6%-16.9%) of their time in light physical activity, and 0.3% (range, 0.12%-1.36%) of their time in moderate to vigorous physical activity. No statistically significant relationships were observed between expected level of function and recorded activity level. Patients had low physical and emotional Short Form-36 component scores. CONCLUSIONS: Patients with transtibial amputations were extremely sedentary in the early postoperative period despite their immediate postoperative prosthesis dressings. PMID- 27386806 TI - Kinematic Manifestation of Arm-Trunk Performance during Symmetric Bilateral Reaching After Stroke: Within vs. Beyond Arm's Length. AB - OBJECTIVE: The aim of this study was to examine the effect of target distance (within vs. beyond arm's length) on arm and trunk movements during symmetric bilateral reaching in patients with stroke. DESIGN: Eighteen stroke patients and 18 age-matched control participants reached bilaterally to press desk bells placed at 90% and 125% of arm's length. The kinematics of paretic arm and trunk movements and trunk contribution slopes were measured in the start, mid, and end phases of reaching. RESULTS: Target distance significantly affected arm (shoulder flexion and abduction, elbow extension) and trunk (flexion, rotation, and lateral shift) movements in patients with stroke. Significant group differences were also found in trunk contribution slopes in the start and mid phases of reaching to targets beyond arm's length. CONCLUSIONS: Bilateral reaching for targets beyond arm's length may increase shoulder flexion, shoulder abduction, elbow extension, and trunk flexion, but it may also induce unsymmetric trunk rotation and lateral shift to the paretic side, as well as early and excessive trunk contributions in patients with stroke. The findings suggest that for beyond-arm-length reaching, therapists may restrain the trunk until the end phase of reaching and prevent trunk rotation and lateral shift to the paretic side. PMID- 27386807 TI - Physical Medicine and Rehabilitation: The Changing Landscape of Residency and Career. PMID- 27386808 TI - Effects of Home-based Telesupervising Rehabilitation on Physical Function for Stroke Survivors with Hemiplegia: A Randomized Controlled Trial. AB - OBJECTIVE: The aims of this work were to evaluate the effects of home-based telesupervising rehabilitation on physical function for stroke survivors with hemiplegia and to determine if the rehabilitation therapy can relieve the burden on caregivers. DESIGN: This study is a randomized, controlled, assessor-blinded trial. Stroke survivors were randomly assigned to either home-based telesupervising rehabilitation group or conventional rehabilitation group to receive physical exercise and electromyography-triggered neuromuscular stimulation. Modified Barthel Index, Berg Balance Scale, modified Rankin Scale, Caregiver Strain Index, root mean square of extensor carpi radialis longus and tibialis anterior muscle were measured at 3 time points: baseline, postintervention (12 weeks), and 12-week follow-up (24 weeks). RESULTS: Both the home-based telerehabilitation and conventional rehabilitation groups demonstrated significant effects within groups over the 3 time points in increasing Modified Barthel Index, Berg Balance Scale, and root mean square value of extensor carpi radialis longus and tibialis anterior, as well as decreasing Caregiver Strain Index (P < 0.001), but none of the between-group differences was significant. For modified Rankin Scale, the percentage of participants of grades 0 and 1 in 2 groups increased over time without significant difference between the groups. CONCLUSIONS: Home-based telesupervising rehabilitation is most likely as effective as the conventional outpatient rehabilitation for improving functional recovery in stroke survivors and could ease the burden of caregivers as conventional rehabilitation. PMID- 27386809 TI - Velopharyngeal Incoordination Caused by Phenytoin-Induced Toxicity. AB - Phenytoin induces lymphoid proliferation, resulting in complications that can range from tissue hyperplasia to lymphoma. Some of the complications resolve spontaneously after drug discontinuation. This report describes for the first time a case of dysphagia with lack of velopharyngeal coordination and nasopharyngeal reflux combined with massive palatine tonsillar hypertrophy. The condition did not develop before phenytoin administration, was induced by phenytoin, and spontaneously resolved upon drug discontinuation. The patient was referred for a video-fluoroscopic swallowing study owing to a recurring nasal reflux of foods that had developed since phenytoin administration. The video fluoroscopic swallowing study revealed incidentally that the large bilateral elongated masses extended downward into the larynx and disturbed velar elevation. This finding was confirmed by computed tomography of the neck, which showed that palatine tonsillar hypertrophy disturbed the laryngopharynx on both sides. The symptoms (sleep apnea and nasal reflux) and the abnormal imaging findings disappeared without surgery approximately 1 month after drug discontinuation. This case suggests that dysphagia related to phenytoin-induced lymphoid hypertrophy may be treated by phenytoin discontinuation followed by a sufficient amount of time to allow symptom resolution rather than by prompt surgery. PMID- 27386810 TI - Accelerated Arterial Stiffening Change in Early Years of Spinal Cord Injury. AB - Patients with spinal cord injury (SCI) possess higher arterial stiffness index (SI) than the healthy population. This study aimed to clarify the effect of post morbid duration on arterial stiffening change among SCI sufferers. Seventy-one SCI patients were recruited. The demographic data including age, gender, level of injury, body mass index, American Spinal Cord Injury Association Impairment Scale, and post-morbid duration were collected. The age was 36.4 +/- 11.7 years and the duration was 87.5 +/- 106.4 months. SI was assessed with digital volume pulse analysis. Correlation matrix demonstrated that age is the most significant determinant of SI (R = 0.503). The scatter plot of duration versus SI showed that they were correlated significantly, but in a logarithmic rather than linear trend. Partial correlation showed that the natural log of duration (Lnduration) has higher adjusted correlation coefficient (0.357) than duration when the effect of age and other factors were eliminated. Multiple linear regression modeling also exhibited that Lnduration is the only factor that significantly increases the explanation of SI by age. In conclusion, Lnduration is an independent determinant of SI. SCI accelerates vascular aging especially in the early several years. Therefore, there should be emphasis on primary prevention of cardiovascular disorders during early years of SCI. PMID- 27386811 TI - Effectiveness of Aquatic Exercises in Women With Rheumatoid Arthritis: A Randomized, Controlled, 16-Week Intervention-The HydRA Trial. AB - OBJECTIVE: The purpose of this study was to compare the effectiveness of land based (LB) and water-based (WB) aerobic exercises in women with rheumatoid arthritis (RA). DESIGN: A total of 133 women with RA were included in this randomized, blinded, prospective, 16-week controlled trial. The subjects were randomized into 3 groups: WB (n = 33), LB (n = 33), and control (n = 34). Muscle strength (MS) was measured using an isokinetic dynamometer. Disease activity (DAS 28) and functional ability (health assessment questionnaire) were measured by an expert rheumatologist. Total body densitometry was used to assess body composition. The intervention was performed 3 times per week, and all groups were evaluated at baseline and after 8 and 16 weeks. Compliance, concomitant medications, and adverse events were recorded. The data were analyzed by intention to treat. P < 0.05 was set as significant. RESULTS: Of the 133 patients recruited, 100 were randomized and 82 completed the study. In the first evaluation, the 3 groups were matched to age, body composition, functional capacity, MS, and concomitant medications. After 16 weeks, there were no significant changes of knee MS neither body composition among the groups. However, there was a significant improvement in disease activity and functional ability in the WB after 8 and 16 weeks. CONCLUSION: Aquatic exercises provided significant improvement in disease activity, pain, and functional capacity. PMID- 27386813 TI - Hemodynamic, Autonomic, Ventilatory, and Metabolic Alterations After Resistance Training in Patients With Coronary Artery Disease: A Randomized Controlled Trial. AB - OBJECTIVE: The aim of this work was to evaluate the hemodynamic, autonomic, and metabolic responses during resistance and dynamic exercise before and after an 8 week resistance training program using a low-intensity (30% of 1 repetitium maximum), high-repetition (3 sets of 20 repetitions) model, added to an aerobic training program, in a coronary artery disease cohort. DESIGN: Twenty male subjects with coronary artery disease (61.1 +/- 4.7 years) were randomly assigned to a combined training group (resistance + aerobic) or aerobic training group (AG). Heart rate, stroke volume, cardiac output, minute ventilation, blood lactate, and parasympathetic modulation indices of heart rate (square root of the mean squared differences of successive RR intervals [RMSSD] and dispersion of points perpendicular to the line of identity that provides information about the instantaneous beat-to-beat variability [SD1]) were obtained before and after an 8 week RT program while performing exercise on a cycle ergometer and a 45-degree leg press. RESULTS: Resistance training resulted in an increase in maximal and submaximal load tolerance (P < 0.01), a decreased hemodynamic response (P < 0.01), and a reduction in blood lactate in the combined training group compared to the aerobic training group during the 45-degree leg press. During exercise on a cycle ergometer, there was a decreased hemodynamic response and increased minute ventilation (P < 0.01). The 8-week RT program resulted in greater parasympathetic tone (RMSSD and SD1) and an increase in the SDNN index during exercise on a cycle ergometer and 45-degree leg press (P < 0.05). CONCLUSIONS: An 8-week resistance training program associated with aerobic training may attenuate hemodynamic stress, and modify metabolic and autonomic responses during resistance exercise. The training program also appeared to elicit beneficial cardiovascular and autonomic effects during exercise. PMID- 27386812 TI - The Diagnostic Accuracy of Special Tests for Rotator Cuff Tear: The ROW Cohort Study. AB - OBJECTIVE: The aim was to assess diagnostic accuracy of 15 shoulder special tests for rotator cuff tears. DESIGN: From February 2011 to December 2012, 208 participants with shoulder pain were recruited in a cohort study. RESULTS: Among tests for supraspinatus tears, Jobe test had a sensitivity of 88% (95% confidence interval [CI], 80%-96%), specificity of 62% (95% CI, 53%-71%), and likelihood ratio of 2.30 (95% CI, 1.79-2.95). The full can test had a sensitivity of 70% (95% CI, 59%-82%) and a specificity of 81% (95% CI, 74%-88%). Among tests for infraspinatus tears, external rotation lag signs at 0 degrees had a specificity of 98% (95% CI, 96%-100%) and a likelihood ratio of 6.06 (95% CI, 1.30-28.33), and the Hornblower sign had a specificity of 96% (95% CI, 93%-100%) and likelihood ratio of 4.81 (95% CI, 1.60-14.49). CONCLUSIONS: Jobe test and full can test had high sensitivity and specificity for supraspinatus tears, and Hornblower sign performed well for infraspinatus tears. In general, special tests described for subscapularis tears have high specificity but low sensitivity. These data can be used in clinical practice to diagnose rotator cuff tears and may reduce the reliance on expensive imaging. PMID- 27386814 TI - Effects of Game-Based Constraint-Induced Movement Therapy on Balance in Patients with Stroke: A Single-Blind Randomized Controlled Trial. AB - OBJECTIVE: The aims of this work were to determine whether game-based constraint induced movement therapy (CIMT) is effective at improving balance ability in patients with stroke, and to provide clinical knowledge of game-based training that allows application of CIMT to the lower extremities. DESIGN: Thirty-six patients with chronic stroke were randomly assigned to game-based CIMT (n = 12), general game-based training (n = 12), and conventional (n = 12) groups. All interventions were conducted 3 times a week for 4 weeks. The static balance control and weight-bearing symmetry were assessed, and the Functional Reach Test (FRT), modified Functional Reach Test (mFRT), and Timed Up and Go (TUG) test were performed to evaluate balance ability. RESULTS: All 3 groups showed significant improvement in anterior-posterior axis (AP-axis) distance, sway area, weight bearing symmetry, FRT, mFRT, and TUG test after the intervention (P < 0.05). Post hoc analysis revealed significant differences in AP-axis, and sway area, weight bearing symmetry of the game-based CIMT group compared with the other group (P < 0.05). CONCLUSIONS: Although the general game-based training and the game-based CIMT both improved on static and dynamic balance ability, game-based CIMT had a larger effect on static balance control, weight-bearing symmetry, and side-to side weight shift. PMID- 27386815 TI - Effectiveness of Global Postural Re-education for Treatment of Spinal Disorders: A Meta-analysis. AB - OBJECTIVE: The aim of this study was to investigate the effects of global postural re-education (GPR) on the treatment of spinal disorders by performing a systematic review and a meta-analysis. DESIGN: MEDLINE, Scopus, and PEDro databases were searched without language or publication date restrictions. Data on pain and function were used to evaluate the effectiveness of GPR. Randomized controlled trials and controlled clinical trials analyzing the effectiveness of GPR on spinal disorders were selected. The standardized mean difference (SMD) and the corresponding 95% confidence interval (95% CI) were calculated. The meta analysis was performed using the Comprehensive Meta-analysis 3.3 software. RESULTS: Seven randomized controlled trials and 4 controlled clinical trials were included in the meta-analysis. The results showed a medium improvement on pain (SMD = -0.63; 95% CI, -0.43 to -0.83) and function (SMD = -0.48; 95% CI, -0.25 to -0.72) after GPR treatment. The positive effect, which was greater in patients with ankylosing spondylitis followed by low back pain and neck pain, was more significant during the intermediate follow-up than immediately after treatment. CONCLUSIONS: This meta-analysis provides reliable evidence that GPR may be an effective method for treating spinal disorders by decreasing pain and improving function. PMID- 27386816 TI - Demonstration of Injury of the Corticospinal Tract in a Patient with Suspected Motor Conversion Disorder. PMID- 27386817 TI - Evaluation of Posterosuperior Labral Tear with Shoulder Sonography After Intra articular Injection: A Case Series. AB - Detection of a posterior glenoid labral lesion can be challenging. Clinicians may overlook this diagnosis because of its vague symptoms, unlike rotator cuff tear or adhesive capsulitis. Together with magnetic resonance (MR) imaging, shoulder MR arthrography is considered the imaging method of choice for the detection of posterior glenoid labral lesions. However, MR arthrography is associated with high cost and low accessibility, and to circumvent these shortcomings, efforts are being made to use sonography (US). However, prior experience in shoulder US is required to evaluate glenoid labrum using US because glenoid labrum is not located superficially and is surrounded by the rotator cuff musculature. There were a few studies that reported the potential for arthrosonography in finding the tear of anterior glenoid labrum and rotator cuff. Until now, however, there was no report regarding arthrosonography in posterosuperior glenoid labral tear and its efficacy and potential for overcoming the limitations of conventional US. In this report, we described 3 cases with posterosuperior glenoid labral tear that were not diagnosed by conventional US but by arthrosonography. In addition, the authors also present their history, physical examinations, and response to treatment, which may be helpful in the diagnosis of posterosuperior glenoid labral tear. PMID- 27386818 TI - Ultrasound Imaging for Prompt Clinical Decision Making Before Interventions. PMID- 27386820 TI - Magnetoresistive polyaniline-silicon carbide metacomposites: plasma frequency determination and high magnetic field sensitivity. AB - The Drude model modified by Debye relaxation time was introduced to determine the plasma frequency (omegap) in the surface initiated polymerization (SIP) synthesized beta-silicon carbide (beta-SiC)/polyaniline (PANI) metacomposites. The calculated plasma frequency for these metacomposites with different loadings of beta-SiC nanoparticles was ranging from 6.11 * 10(4) to 1.53 * 10(5) rad s( 1). The relationship between the negative permittivity and plasma frequency indicates the existence of switching frequency, at which the permittivity was changed from negative to positive. More interestingly, the synthesized non magnetic metacomposites, observed to follow the 3-dimensional (3-D) Mott variable range hopping (VRH) electrical conduction mechanism, demonstrated high positive magnetoresistance (MR) values of up to 57.48% and high MR sensitivity at low magnetic field regimes. PMID- 27386819 TI - Fractalkine restores the decreased expression of StAR and progesterone in granulosa cells from patients with polycystic ovary syndrome. AB - Low progesterone levels are associated with luteal phase deficiency in women with polycystic ovary syndrome (PCOS). The mechanisms regulating progesterone biosynthesis in the granulosa cells from women with PCOS is largely unknown. Fractalkine is expressed in human ovaries, and is reported to regulate progesterone production in granulosa cells of healthy women. In the current study, we aimed to examine the role of fractalkine in women with PCOS. Reduced fractalkine levels were found in follicular fluid and granulosa cells, accompanied by decreased progesterone production and reduced steroidogenic acute regulatory protein (StAR) expression in the granulosa cells of patients with PCOS. Administration of fractalkine reversed the inhibition of progesterone and StAR expression. The mechanism mediating these effects may be associated with the inhibition of ERK activity in the granulosa cells from women with PCOS. Our findings revealed that fractalkine regulated steroidogenesis in follicular granulosa cells of women with PCOS. PMID- 27386821 TI - The Glycated Albumin (GA) to HbA1c Ratio Reflects Shorter-Term Glycemic Control than GA: Analysis of Patients with Fulminant Type 1 Diabetes. AB - BACKGROUND: Glycated albumin (GA) reflects shorter-term glycemic control than HbA1c. We have reported that HbA1c is paradoxically increased in diabetic patients whose glycemic control deteriorated before ameliorating. In this study, we analyzed paradoxical increases of glycemic control indicators after treatment in patients with fulminant type 1 diabetes (FT1D). We also investigated whether the GA/HbA1c ratio may reflect shorter-term glycemic control than GA. METHODS: Five FT1D patients whose post-treatment HbA1c and GA levels were measured were enrolled. We also used a formula to estimate HbA1c and GA from the fictitious models of changes in plasma glucose in FT1D patients. In this model, the periods during which HbA1c, GA, and the GA/HbA1c ratio were higher than at the first visit were compared. In addition, the half-life for the GA/HbA1c ratio was calculated in accordance with the half-lives for HbA1c and GA (36 and 14 days, respectively). RESULTS: In all FT1D patients, HbA1c levels 2-4 weeks after treatment were increased, with three patients (60%) experiencing an increase of GA levels. In contrast, an increase of the GA/HbA1c ratio was observed in only one patient. In all of the different models of changes in plasma glucose in FT1D patients, the length of time during which the values were higher than at the first visit was in the order of HbA1c > GA > GA/HbA1c ratio. The half-life for the GA/HbA1c ratio was 9 days, shorter than GA. CONCLUSIONS: These findings suggest that the GA/HbA1c ratio reflects shorter-term glycemic control than GA. PMID- 27386822 TI - Jitter values in infants. PMID- 27386824 TI - CE-C(4)D method development and validation for the assay of ciprofloxacin. AB - A capillary electrophoresis method with capacitively coupled contactless conductivity detection (CE-C(4)D) has been developed, optimized and validated for the determination of ciprofloxacin. Ciprofloxacin is a member of the fluoroquinolone antibiotics with a broad spectrum bactericidal activity and recommended for complicated respiratory infections, sexually transmitted diseases, tuberculosis, bacterial diarrhea etc. Method development was conducted with major focus on the quality by design (QbD) approach. During method development, multiple buffers were tried at different ionic strength. However, the optimized method finally involved a very simple background electrolyte, monosodium citrate at a concentration of 10mM without pH adjustment. The optimized CE-C(4)D method involved an uncoated fused silica capillary (59/39cm, 50MUm i.d.) and hydrodynamic sample injection at a pressure of 0.5 p.s.i. for 5s. The actual separation was conducted for 10min at normal polarity with a voltage of 20kV corresponding to 5.9MUA current. LiCl (1mg/mL) was used as an internal standard. The optimized method is robust and accurate (recovery >98%) which rendered the ciprofloxacin peak within five minutes with good linearity (R(2)>0.999) in the concentration range of 0.0126-0.8mg/mL. The repeatability is expressed by percentage relative standard deviation (%RSD) of the relative peak areas (RPA) and it showed good repeatability both intra-day (<3%) and inter-day (3.1%). This method, proven to be free of matrix interference, showed that the estimated percent content of ciprofloxacin (102%) was within the official requirements. Moreover, due to its ease of use and robustness, the method should also be applicable in less well controlled laboratory environments. PMID- 27386825 TI - Identification of a reference gene for the quantification of mRNA and miRNA expression during skin wound healing. AB - AIM: Wound healing is a coordinated process to restore tissue homeostasis and reestablish the protective barrier of the skin. miRNAs may modulate the expression of target genes to contribute to repair processes, but due to the complexity of the tissue it is challenging to quantify gene expression during the distinct phases of wound repair. Here, we aimed to identify a common reference gene to quantify changes in miRNA and mRNA expression during skin wound healing. METHODS: Quantitative real-time PCR and bioinformatic analysis tools were used to identify suitable reference genes during skin repair and their reliability was tested by studying the expression of mRNAs and miRNAs. RESULTS: Morphological assessment of wounds showed that the injury model recapitulates the distinct phases of skin repair. Non-degraded RNA could be isolated from skin and wounds and used to study the expression of non-coding small nuclear RNAs during wound healing. Among those, RNU6B was most constantly expressed during skin repair. Using this reference gene we could confirm the transient upregulation of IL-1beta and PTPRC/CD45 during the early phase as well as the increased expression of collagen type I at later stages of repair and validate the differential expression of miR-204, miR-205, and miR-31 in skin wounds. In contrast to Gapdh the normalization to multiple reference genes gave a similar outcome. CONCLUSION: RNU6B is an accurate alternative normalizer to quantify mRNA and miRNA expression during the distinct phases of skin wound healing when analysis of multiple reference genes is not feasible. PMID- 27386823 TI - Integrative functional genomics identifies regulatory mechanisms at coronary artery disease loci. AB - Coronary artery disease (CAD) is the leading cause of mortality and morbidity, driven by both genetic and environmental risk factors. Meta-analyses of genome wide association studies have identified >150 loci associated with CAD and myocardial infarction susceptibility in humans. A majority of these variants reside in non-coding regions and are co-inherited with hundreds of candidate regulatory variants, presenting a challenge to elucidate their functions. Herein, we use integrative genomic, epigenomic and transcriptomic profiling of perturbed human coronary artery smooth muscle cells and tissues to begin to identify causal regulatory variation and mechanisms responsible for CAD associations. Using these genome-wide maps, we prioritize 64 candidate variants and perform allele-specific binding and expression analyses at seven top candidate loci: 9p21.3, SMAD3, PDGFD, IL6R, BMP1, CCDC97/TGFB1 and LMOD1. We validate our findings in expression quantitative trait loci cohorts, which together reveal new links between CAD associations and regulatory function in the appropriate disease context. PMID- 27386826 TI - Strategies to improve outcomes for hepatitis C virus/human immunodeficiency virus coinfected liver transplant candidates. PMID- 27386827 TI - The report on the Universal Neonatal Hearing Screening Program in Poland between 2003 and 2015. AB - The Universal Neonatal Hearing Screening Program (UNHSP) has been operating in the whole Poland since 2003. Its main goals are to perform a screening hearing in the 2-3 day of life in every newborn baby in Poland and to gather information on risk factors of hearing loss. In total, 505 centers participate in the UNHSP on three reference levels. As of January 19th 2016, the central data base (CDB) of the UNHSP has records of 4,845,036 children, which comprises 96% of all children born in Poland. Hearing loss was diagnosed in 12,974 children, i.e. in 3 out of 1000 children. Here, we present the most important results and conclusions of the UNHSP. PMID- 27386828 TI - Nose underdevelopment - etiology, diagnosis and treatment. AB - INTRODUCTION: Clinical picture of nose underdevelopment is very polymorphic. It can exist from partial disturbances of nose development, through unilateral hypoplasia of the nose to congenital absence of the nose (arhinia). AIM: The aim of this study is to present own experience of treatment of patients with different types of nose underdevelopment. MATERIAL AND METHOD: Plastic Surgery Out-patient Clinic has under care 13 patients with isolated nose underdevelopment. In this group there were 5 men and 8 women. The patients' age, at the time of first consultation, was from 6 months to 19 years. RESULTS: The most frequent type of defect in analyzed group was congenital saddle nose (6 persons). Three patients were diagnosed with absence of the quadrilateral cartilage of the nasal septum, two with isolated underdevelopment of the alar cartilage and one with bilateral underdevelopment of the nasal bones. The most advanced disturbance was observed in 6 months old girl, who had unilateral hypoplasia of the nose. Nine patients were surgically treated. CONCLUSIONS: Nose underdevelopment is rare congenital anomaly and is characterized by variable clinical picture. Medical history and precise physical examination are fundamental in proper diagnosis. Disturbances in nose development can lead to serious functional consequences and require individual plan of treatment. PMID- 27386829 TI - Correlations between Apnea/Hypopnea Index and selected morphological and clinical parameters in patients with unilateral or bilateral impairment of nasal patency. AB - INTRODUCTION: The aim of this work was to evaluate the correlation between Apnea/Hypopnea Index (AHI) and selected parameters of morphological and clinical character in the patients with a unilateral or bilateral impairment of nasal patency. MATERIAL AND METHODS: The study covered 60 adults, including 37 male and 23 female subjects, 19-69 years of age. In the Department, these subjects were divided into 3 groups: I - 20 patients with unilateral impairment of nasal patency, II - 20 patients with bilateral impairment of nasal patency, III - controls with normal nasal patency. METHODOLOGY: A subjective examination (questionnaire with a sleepiness scale), an objective examination (general examination of the neck and waist diameter, body weight, height, length of the uvula), otorhinolaryngological examination (Pirquet test of the palatine tonsils), X-ray and CT of the head and paranasal sinuses) to determine the cause and location of the obturation of air passages, physiological tests and polysomnography. The correlations between the neck circumferenceheight ratio (NHR) and AHI, waist-hip ratio (WHR) and AHI. The statistical analysis of the study results was conducted in Stata(r)/Special Edition Program, 14.1 version (StataCorp LP, College Station, Texas, USA). RESULTS: Clinically, the study group revealed: shallow breathing in 47.5% and apnea in 52.5% of the studied patients whereas the control group did not show any sleep disorders. Statistical fluctuations between controls and the study groups were noticed (p<0.001). CONCLUSION: By the Epworth scale, moderate and severe sleepiness was found in merely 12.5% of the patients. The differences in the length of the uvula and the size of the pharyngeal tonsils between the studied groups were not statistically significant. No statistical significance was found between NHR and AHI, BMI and AHI, WHR and AHI in the studied group. PMID- 27386830 TI - Deep neck infections - still important diagnostic and therapeutic problem. AB - Deep neck infections (DNI) are serious problem because of variable clinical manifestations. This condition affects fascial compartments of the head and neck and organs that they contain. Nowadays the incidence of DNI have decreased because of antibiotics use and improvements in oral hygiene. But it may still lead to many life-threatening complications due to numerous portals of entry and proximity to vital structures. Furthermore, the inappropriate use of antibiotics, steroids, and nonsteroidal anti-inflammatory drugs may mask signs of infection and change the clinical presentation, and also lead to a different courses of disease. In the literature, especially in complicated cases, the mortality may range up to 42%. PMID- 27386831 TI - Polysomnographic evaluation of sleep apnea in patients with unilateral or bilateral impaired nasal patency. AB - INTRODUCTION: The aim of this work was to describe the polysomnographic evaluation of sleep apnea in patients suffering from unilateral or bilateral impaired nasal passage patency. MATERIAL AND METHODS: The study covered 60 adult, including 23 women and 37 men aged 19-69, admitted to the Hospital Department. The subjects were divided into 3 groups: I - 20 patients with unilateral impaired nasal patency, II - 20 patients with bilateral impaired nasal patency, III - 20 controls with correct nasal passage patency. The methodology of the study included: a subjective examination, a questionnaire with questions about main night symptoms, e.g. dyspnea, noisy snoring, polynuria, an objective examination, blood tests (morphology, CRP, fibrinogen, IL-6, glucose level), imaging tests (RTG, CT and MRI of the head/paranasal sinuses) to determine the cause and site of respiratory obturation, physiological tests as a part of polysomnogram. The analysis described: the level of sleep disorders, causes associated with impaired nasal patency and the Mladina's classification of the nasal septum deviation. RESULTS: Due to the conducted polysomnogram and analysis of the additional tests, sleep apnea was diagnosed in the studied patients with impaired nasal patency: shallow breathing u 19 patients (47,5%) with unilateral impaired patency and 9 patients (22,5%) with bilateral impaired patency, whereas apnea in 21 patients (52,5%) with unilateral impaired patency and 11 patients (27,5%) with bilateral impaired patency. In both groups I and II, the impaired nasal passage patency was caused by nasal septum deviation in 18 cases (34%) and in 15 cases (28,3%), respectively. The control group did not show any sleep disorders in polysomnographic tests. Each patient from group I and II was referred for surgery to improve the nasal patency due to its cause. CONCLUSION: The conducted tests revealed shallow breathing in 47,5% of the studied patients whereas sleep apnea in 52,5% cases. The most frequent cause of impaired nasal patency was nasal septum deviation, which was found in 82,5% of the patients, including 45% with unilateral impaired patency and 37,5% with bilateral nasal patency. PMID- 27386832 TI - Non-human leukocyte antigen-specific antibodies in thoracic transplantation. AB - PURPOSE OF REVIEW: Development of donor human leukocyte antigen (HLA)-specific antibodies is associated with graft loss, yet the role of non-HLA antibodies in solid organ transplant needs to be further defined. It is suggested that HLA antibodies and non-HLA antibodies collaborate together to impact graft outcome. This review focuses on the latest findings on antibodies against these non-HLA antigens in thoracic organ transplant. RECENT FINDINGS: These non-HLA antigens include signaling proteins expressed on the cell surface, such as angiotensin II type 1 receptor (AT1R), endothelin type A receptor, and structure proteins, such as myosin, vimentin, and Kalpha1 tubulin, and extracellular matrix protein collagen. Antibodies against these antigens may impact the allograft in different ways. Although these non-HLA antibodies can damage the allograft through complement-mediated or cell-mediated cytotoxicity, antibodies against AT1R and endothelin type A receptor can also alter the endothelial cell function by activating intracellular signals. The presence of these non-HLA antibodies may predispose the patient to develop HLA-specific antibodies. Recently, it has been shown patients with AT1R antibodies pretransplant have a higher chance to develop de-novo donor-specific HLA antibodies. SUMMARY: The findings suggest it is important to stratify the patient's immunologic risk by assessing both the HLA and non-HLA-specific antibodies. PMID- 27386833 TI - A New Approach in Applying Systems Engineering Tools and Analysis to Determine Hepatocyte Toxicogenomics Risk Levels to Human Health. AB - There is an increasing backlog of potentially toxic compounds that cannot be evaluated with current animal-based approaches in a cost-effective and expeditious manner, thus putting human health at risk. Extrapolation of animal based test results for human risk assessment often leads to different physiological outcomes. This article introduces the use of quantitative tools and methods from systems engineering to evaluate the risk of toxic compounds by the analysis of the amount of stress that human hepatocytes undergo in vitro when metabolizing GW7647 1 over extended times and concentrations. Hepatocytes are exceedingly connected systems that make it challenging to understand the highly varied dimensional genomics data to determine risk of exposure. Gene expression data of peroxisome proliferator-activated receptor-alpha (PPARalpha) 2 binding was measured over multiple concentrations and varied times of GW7647 exposure and leveraging mahalanombis distance to establish toxicity threshold risk levels. The application of these novel systems engineering tools provides new insight into the intricate workings of human hepatocytes to determine risk threshold levels from exposure. This approach is beneficial to decision makers and scientists, and it can help reduce the backlog of untested chemical compounds due to the high cost and inefficiency of animal-based models. PMID- 27386834 TI - Lessons of Risk Communication and Health Promotion - West Africa and United States. AB - During the response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa, CDC addressed the disease on two fronts: in the epidemic epicenter of West Africa and at home in the United States. Different needs drove the demand for information in these two regions. The severity of the epidemic was reflected not only in lives lost but also in the amount of fear, misinformation, and stigma that it generated worldwide. CDC helped increase awareness, promoted actions to stop the spread of Ebola, and coordinated CDC communication efforts with multiple international and domestic partners. CDC, with input from partners, vastly increased the number of Ebola communication materials for groups with different needs, levels of health literacy, and cultural preferences. CDC deployed health communicators to West Africa to support ministries of health in developing and disseminating clear, science-based messages and promoting science-based behavioral interventions. Partnerships in West Africa with local radio, television, and cell phone businesses made possible the dissemination of messages appropriate for maximum effect. CDC and its partners communicated evolving science and risk in a culturally appropriate way to motivate persons to adapt their behavior and prevent infection with and spread of Ebola virus. Acknowledging what is and is not known is key to effective risk communication, and CDC worked with partners to integrate health promotion and behavioral and cultural knowledge into the response to increase awareness of the actual risk for Ebola and to promote protective actions and specific steps to stop its spread. The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html). PMID- 27386835 TI - Hospitalization and mortality due to hepatitis A in Taiwan: a 15-year nationwide cohort study. AB - Hepatitis A virus (HAV) is the most common food-borne hepatitis in the world. The study objectives were (i) to describe the epidemiology of HAV-related hospitalizations during 1997-2011 in Taiwan, (ii) to examine the age effect on the length of stay (LOS) in hospital and (iii) to study the factors associated with death. The hospitalized cases were identified from the Taiwan National Health Insurance Research Database between 1997 and 2011 by ICD-9-CM code of 070.0/070.1. Patient sex, birthday, dates of hospitalization and death were analysed. A total of 3990 HAV-hospitalized cases, males 2467 (62%), were identified. The LOS increased as patients' age increased. The overall mortality rate was 16.8 per 1000 hospitalizations. Males had significantly higher case fatality rate than females (20.7 vs 10.5 per 1000 cases). The adjusted odds ratio (aOR) for death rose by age and increased rapidly over 40 years of age. The aOR and 95% confidence interval [95%CI] for aged 40-59 years and aged over 60 years were 7.89 (1.06-58.98) and 14.88 (2.02-109.40) compared to aged 0-19 years, respectively. Patients with chronic liver disease and cirrhosis had significantly higher risk of death (aOR=1.03 [1.01-1.04]), compared to those without liver disease. However, patients with liver disease, but no cirrhosis did not have higher risk of death (aOR=1.00 [0.99-1.01]). The aOR [95%CI] for LOS >9 day was 3.26 (1.96-5.40) compared to cases with LOS <=9 days. Male sex, age over 40 years, cirrhotic liver and long LOS are significant factors associated with death in HAV-hospitalized cases. PMID- 27386836 TI - Short-term predictive ability of selected cardiovascular risk prediction models in a rural Bangladeshi population: a case-cohort study. AB - BACKGROUND: Prediction of absolute risk of cardiovascular diseases (CVDs) has important clinical and public health significance, but the predictive ability of the available tools has not yet been tested in the rural Bangladeshi population. The present study was undertaken to test the hypothesis that both laboratory based (Framingham equation and WHO/ISH laboratory-based charts) and non laboratory-based tools may be used to predict CVDs on a short-term basis. METHODS: Data from a case-cohort study (52989 cohort and 439 sub-cohort participants), conducted on a rural Bangladeshi population, were analysed using modified Cox PH model with a maximum follow-up of 2.5 years. The outcome variable, coronary heart diseases (CHDs), was assessed in 2014 using electrocardiography, and it was used as a surrogate marker for CVDs in Bangladesh. The predictive power of the models was assessed by calculating C statistics and generating ROC curves with other measures of diagnostic tests. RESULTS: All the models showed high negative prediction values (NPVs, 84 % to 92 %) and these did not differ between models or gender. The sensitivity of the models substantially changed based on the risk prediction thresholds (between 5 30 %); however, the NPVs and PPVs were relatively stable at various threshold levels. Hypertension and dyslipidaemia were significantly associated with CHD outcome in males and ABSI (a body shape index) in females. All models showed similar C-statistics (0.611-0.685, in both genders). Overall, the non-laboratory based model showed better performance (0.685) in women but equal performance in men. CONCLUSIONS: Existing CVD risk prediction tools may identify future CHD cases with fairly good confidence on a short-term basis. The non-laboratory-based tool, using ABSI as a predictor, may provide better predictive accuracy among women. PMID- 27386837 TI - Development of solid-phase microextraction coupled with liquid chromatography for analysis of tramadol in brain tissue using its molecularly imprinted polymer. AB - In this work, performance of a molecularly imprinted polymer (MIP) as a selective solid-phase microextraction sorbent for the extraction and enrichment of tramadol in aqueous solution and rabbit brain tissue, is described. Binding properties of MIPs were studied in comparison with their nonimprinted polymer (NIP). Ten milligrams of the optimized MIP was then evaluated as a sorbent, for preconcentration, in molecularly imprinted solid-phase microextraction (MISPME) of tramadol from aqueous solution and rabbit brain tissue. The analytical method was calibrated in the range of 0.004 ppm (4 ng mL-1 ) and 10 ppm (10 MUg mL-1 ) in aqueous media and in the ranges of 0.01 and 10 ppm in rabbit brain tissue, respectively. The results indicated significantly higher binding affinity of MIPs to tramadol, in comparison with NIP. The MISPME procedure was developed and optimized with a recovery of 81.12-107.54% in aqueous solution and 76.16-91.20% in rabbit brain tissue. The inter- and intra-day variation values were <8.24 and 5.06%, respectively. Finally the calibrated method was applied for determination of tramadol in real rabbit brain tissue samples after administration of a lethal dose. Our data demonstrated the potential of MISPME for rapid, sensitive and cost effective sample analysis. PMID- 27386838 TI - Dual focused coherent beams for three-dimensional optical trapping and continuous rotation of metallic nanostructures. AB - Metallic nanoparticles and nanowires are extremely important for nanoscience and nanotechnology. Techniques to optically trap and rotate metallic nanostructures can enable their potential applications. However, because of the destabilizing effects of optical radiation pressure, the optical trapping of large metallic particles in three dimensions is challenging. Additionally, the photothermal issues associated with optical rotation of metallic nanowires have far prevented their practical applications. Here, we utilize dual focused coherent beams to realize three-dimensional (3D) optical trapping of large silver particles. Continuous rotation of silver nanowires with frequencies measured in several hertz is also demonstrated based on interference-induced optical vortices with very low local light intensity. The experiments are interpreted by numerical simulations and calculations. PMID- 27386840 TI - A new strategy for the decellularisation of large equine tendons as biocompatible tendon substitutes. AB - Tendon ruptures and/or large losses remain to be a great clinical challenge and often require full replacement of the damaged tissue. The use of auto- and allografts or engineered scaffolds is an established approach to restore severe tendon injuries. However, these grafts are commonly related to scarce biocompatibility, site morbidity, chronic inflammation and poor biomechanical properties. Recently, the decellularisation techniques of allo- or xenografts using specific detergents have been studied and have been found to generate biocompatible substitutes that resemble the native tissue. This study aims to identify a novel decellularisation protocol for large equine tendons that would produce an extracellular matrix scaffold suitable for the regeneration of injured tendons in humans. Specifically, equine tendons were treated either with tri (n butyl) phosphate alone, or associated to multiple concentrations of peracetic acid (1, 3 and 5 %), which has never before been tested in vitro.Samples were then analysed by histology and with biochemical, biomechanical, and cytotoxicity tests. The best decellularisation protocol, resulting from these examinations, was selected and the chosen scaffold was re-seeded with murine fibroblasts. Resulting grafts were tested for cell viability, histologic analysis, DNA and collagen content. The results identified 1 % tri (n-butyl) phosphate combined with 3 % peracetic acid as the most suitable decellularised matrix in terms of biochemical and biomechanical properties. Moreover, the non-cytotoxic nature of the decellularised matrix allowed for good fibroblast reseeding, thus demonstrating a biocompatible matrix that will be suitable for tendon tissue engineering and hopefully as substitutes in severe tendon damages. PMID- 27386839 TI - Obstetric and offspring risks of women's morbid conditions linked to prior anticancer treatments. AB - BACKGROUND: Literature shows the effects of type of cancer and/or anticancer treatment on live birth percentages and/or pregnancy and neonatal complications in female cancer survivors. However, studies analyzing the obstetric and offspring risks of the morbid conditions associated with previous anti-cancer treatments are missing. The present review aims to uncover these risks. METHODS: A literature search based on publications up to March 2016 identified by PubMed and references cited in relevant articles. RESULTS: The morbid conditions associated with prior anticancer treatments including chemotherapy, radiotherapy, surgery, and/or hematopoietic stem-cell transplant may induce not only obstetric and neonatal complications but also long-term effects on offspring. Whereas some risks are predominantly evidenced in untreated women others are observed in both treated and untreated women. These risks may be superimposed on those induced by the current women's trend in Western societies to postpone maternity. CONCLUSIONS: Medical professionals should be aware and inform female cancer survivors wishing to have a child not only of the short- and long-term risks to themselves and their prospective offspring of previous anticancer treatments, fertility-preservation technologies, and pregnancy itself, but also of those risks linked to the morbid conditions induced by prior anticancer treatments. Once female cancer survivors wishing to have a child have been properly informed about the risks of reproduction, they will be best placed to make decisions of whether or not to have a biological or donor-conceived child. In addition, when medical professionals be aware of these risks, they will be also best placed to provide appropriate treatments before/during pregnancy in order to prevent or alleviate the impact of these morbid conditions on maternal and offspring health. PMID- 27386841 TI - Effects of macrophage-activating lipopeptide-2 (MALP-2) on the vascularisation of implanted polyurethane scaffolds seeded with microvascular fragments. AB - The seeding of scaffolds with adipose tissue-derived microvascular fragments represents a promising strategy to establish a sufficient blood supply in tissue constructs. Herein, we analysed whether a single application of macrophage activating lipopeptide-2 (MALP-2) at the implantation site further improves the early vascularisation of such microvessel-seeded constructs. Microvascular fragments were isolated from epididymal fat pads of C57BL/6 mice. The fragments were seeded on polyurethane scaffolds, which were implanted into mouse dorsal skinfold chambers exposed to MALP-2 or vehicle (control). The inflammatory host tissue response and the vascularisation of the scaffolds were analysed using intravital fluorescence microscopy, histology and immunohistochemistry. We found that the numbers of microvascular adherent leukocytes were significantly increased in MALP-2-treated chambers during the first 3 days after scaffold implantation when compared to controls. This temporary inflammation resulted in an improved vascularisation of the host tissue surrounding the implants, as indicated by a higher density of CD31-positive microvessels at day 14. However, the MALP-2-exposed scaffolds themselves presented with a lower functional microvessel density in their centre. In addition, in vitro analyses revealed that MALP-2 promotes apoptotic cell death of endothelial and perivascular cells in isolated microvascular fragments. Hence, despite the beneficial pro-angiogenic properties of MALP-2 at the implantation site, the herein evaluated approach may not be recommended to improve the vascularisation capacity of microvascular fragments in tissue engineering applications. PMID- 27386843 TI - VSGBI abstracts from The Vascular Societies' Annual Scientific Meeting, 11-13 November 2015. PMID- 27386842 TI - Impact of Combination Epidural and General Anesthesia on the Long-Term Survival of Gastric Cancer Patients: A Retrospective Study. AB - BACKGROUND Whether regional anesthesia is associated with tumor-free and long term survival is controversial. Here, we focused on whether epidural anesthesia affects the long-term survival of gastric cancer patients after surgery. MATERIAL AND METHODS We obtained the records of 273 patients undergoing gastric cancer surgery between August 2006 and December 2010. All patients received elective surgery, and the end-point was death. The general anesthesia group comprised 116 patients and the epidural-supplemented group comprised 157 patients. The results were analyzed using a multivariable model to determine the relationship between epidural use and long-term survival. RESULTS No obvious association was detected between epidural use and long-term survival according to the Cox model (P=0.522); the adjusted estimated hazard ratio was 0.919 (95% CI 0.71-1.19). However, according to Kaplan-Meier analysis, epidural anesthesia was associated with long term survival among younger patients (age up to 64) (p=0.042, log-rank) (but not among older patients (p=0.203, log-rank). A lower American Society of Anesthesiologists (ASA) class and less chemoradiotherapy exposure were also associated with a longer survival. However, advanced tumor stage still has a significant negative impact on survival. CONCLUSIONS No obvious difference was detected between the 2 anesthesia groups, but younger patients may benefit from epidural anesthesia. PMID- 27386844 TI - Metabolic syndrome is associated with advanced prostate cancer in patients treated with radical retropubic prostatectomy: results from a multicentre prospective study. AB - BACKGROUND: Prostate cancer (PCa) is the most common non-skin cancer in USA and the second leading cause of cancer death in Western Countries. Despite the high mortality associated with PCa, the only established risk factors are age, race and family history. A possible association between metabolic syndrome (MetS) and PCa was firstly described in 2004 and several subsequent studies in biopsy cohorts have shown conflicting results. Aim of our multicentre prospective study was to investigate the association between MetS and PCa in men undergoing radical prostatectomy (RP). METHODS: From January 2012 to June 2015, 349 consecutive men undergoing RP for PCa at three centres in Italy were enrolled into a prospective database. Body Mass Index (BMI) as well as waist circumference was measured before RP. Blood samples were also collected and tested for total PSA, fasting glucose, triglycerides and HDLs. Blood pressure was also recorded. We evaluated the association between MetS, defined according to Adult Treatment Panel III, PCa stage (advanced stage defined as pT >= 3 or N1) and grade (high grade defined as Gleason Score >= 4 + 3) using logistic regression analyses. RESULTS: Median age and preoperative PSA levels were 66 years (IQR: 61-69) and 7 ng/ml (IQR: 5-10), respectively. Median BMI was 26.12 kg/m(2) (IQR 24-29) with 56 (16 %) obese (BMI >= 30 kg/m(2)) patients and 87 (25 %) patients with MetS. At pathological evaluation, advanced PCa and high-grade disease were present in 126 (36 %) and 145 (41.5 %) patients, respectively. MetS was significantly associated with advanced PCa (45/87, 51 % vs 81/262, 31 %; p = 0.008) and high-grade disease (47/87, 54 % vs 98/262, 37 %; p = 0.001). On multivariable analysis, MetS was an independent predictor of pathological stage >= pT3a or N1 (OR: 2.227; CI: 1.273 3.893; p = 0.005) and Gleason score >= 4 + 3 (OR: 2.007, CI: 1.175-3.428; p = 0.011). CONCLUSIONS: We firstly demonstrated in a European radical retropubic prostatectomy cohort study that MetS is associated with an increased risk of high grade and advanced prostate cancer. Further studies with long term follow-up should evaluate the impact of Mets on PCa survival. PMID- 27386845 TI - Characterization of CDH3-Related Congenital Hypotrichosis With Juvenile Macular Dystrophy. AB - IMPORTANCE: Congenital hypotrichosis with juvenile macular dystrophy (HJMD) is a rare disorder presenting in childhood and adolescence with central visual disturbance and sparse scalp hair. Reported retinal imaging is lacking, and whether the condition is progressive remains unclear. OBJECTIVE: To investigate a series of patients with HJMD due to biallelic mutations in CDH3 and thereby characterize the disorder. DESIGN, SETTING, AND PARTICIPANTS: Ten patients from 10 families underwent detailed clinical assessment, including serial retinal imaging and electrophysiologic evaluation, at Moorfields Eye Hospital, St James's University Hospital, and Calderdale Royal Infirmary. Patients ranged in age from 3 to 17 years at onset and 5 to 57 years at last assessment. The molecular genetic investigation included bidirectional Sanger sequencing of all exons and intron-exon boundaries of CDH3 and whole-exome sequencing in 2 patients. The study was conducted from June 5, 2013, to January 15, 2016, with final follow-up completed on December 15, 2015. MAIN OUTCOMES AND MEASURES: Results of clinical assessment and molecular genetic testing. RESULTS: All 10 patients (7 male and 3 female) presented with central visual disturbance in childhood and had lifelong sparse scalp hair with normal facial hair. Fundus examination revealed chorioretinal atrophy of the posterior pole contiguous with the disc in all but 1 patient that was associated with marked loss of autofluorescence on fundus autofluorescence imaging. Optical coherence tomography (OCT) demonstrated variable degrees of atrophy of the outer retina, retinal pigment epithelium, and choroid, with outer retinal tubulations frequently observed. One patient had mild disruption of the inner segment ellipsoid band on OCT and additional mild digit abnormalities. Electrophysiologic evaluation in 5 patients demonstrated macular dysfunction with additional mild, generalized retinal dysfunction in 2 patients. Eight patients had more than 1 evaluation; of these, 5 patients showed deterioration of visual acuity over time, 1 patient remained stable, and 2 patients had severe visual loss at presentation that precluded assessment of visual deterioration. The area of atrophy did not progress with time, but retinal thickness decreased on OCT. Electrophysiologic evaluation in 1 patient found deterioration of macular function after 13 years of follow-up, but the mild, generalized photoreceptor dysfunction remained stable. Biallelic mutations were identified in all patients, including 6 novel mutations. CONCLUSIONS AND RELEVANCE: These results suggest that CDH3-related disease is characterized by a childhood-onset, progressive chorioretinal atrophy confined to the posterior pole. The disease is readily distinguished from other juvenile macular dystrophies by the universally thin and sparse scalp hair. Patients may have additional limb abnormalities. PMID- 27386846 TI - Expression and methylation patterns partition luminal-A breast tumors into distinct prognostic subgroups. AB - BACKGROUND: Breast cancer is a heterogeneous disease comprising several biologically different types, exhibiting diverse responses to treatment. In the past years, gene expression profiling has led to definition of several "intrinsic subtypes" of breast cancer (basal-like, HER2-enriched, luminal-A, luminal-B and normal-like), and microarray based predictors such as PAM50 have been developed. Despite their advantage over traditional histopathological classification, precise identification of breast cancer subtypes, especially within the largest and highly variable luminal-A class, remains a challenge. In this study, we revisited the molecular classification of breast tumors using both expression and methylation data obtained from The Cancer Genome Atlas (TCGA). METHODS: Unsupervised clustering was applied on 1148 and 679 breast cancer samples using RNA-Seq and DNA methylation data, respectively. Clusters were evaluated using clinical information and by comparison to PAM50 subtypes. Differentially expressed genes and differentially methylated CpGs were tested for enrichment using various annotation sets. Survival analysis was conducted on the identified clusters using the log-rank test and Cox proportional hazards model. RESULTS: The clusters in both expression and methylation datasets had only moderate agreement with PAM50 calls, while our partitioning of the luminal samples had better five year prognostic value than the luminal-A/luminal-B assignment as called by PAM50. Our analysis partitioned the expression profiles of the luminal-A samples into two biologically distinct subgroups exhibiting differential expression of immune related genes, with one subgroup carrying significantly higher risk for five-year recurrence. Analysis of the luminal-A samples using methylation data identified a cluster of patients with poorer survival, characterized by distinct hyper methylation of developmental genes. Cox multivariate survival analysis confirmed the prognostic significance of the two partitions after adjustment for commonly used factors such as age and pathological stage. CONCLUSIONS: Modern genomic datasets reveal large heterogeneity among luminal breast tumors. Our analysis of these data provides two prognostic gene sets that dissect and explain tumor variability within the luminal-A subgroup, thus, contributing to the advancement of subtype-specific diagnosis and treatment. PMID- 27386847 TI - Psychosocial impact of prognostic genetic testing in the care of uveal melanoma patients: protocol of a controlled prospective clinical observational study. AB - BACKGROUND: Uveal melanoma patients with a poor prognosis can be detected through genetic analysis of the tumor, which has a very high sensitivity. A large number of patients with uveal melanoma decide to receive information about their individual risk and therefore routine prognostic genetic testing is being carried out on a growing number of patients. It is obvious that a positive prediction for recidivism in the future will emotionally burden the respective patients, but research on the psychosocial impact of this innovative method is lacking. The aim of the current study is therefore to investigate the psychosocial impact (psychological distress and quality of life) of prognostic genetic testing in patients with uveal melanoma. DESIGN AND METHODS: This study is a non-randomized controlled prospective clinical observational trial. Subjects are patients with uveal melanoma, in whom genetic testing is possible. Patients who consent to genetic testing are allocated to the intervention group and patients who refuse genetic testing form the observational group. Both groups receive cancer therapy and psycho-oncological intervention when needed. The psychosocial impact of prognostic testing is investigated with the following variables: resilience, social support, fear of tumor progression, depression, general distress, cancer specific and general health-related quality of life, attitude towards genetic testing, estimation of the perceived risk of metastasis, utilization and satisfaction with psycho-oncological crisis intervention, and sociodemographic data. Data are assessed preoperatively (at initial admission in the clinic) and postoperatively (at discharge from hospital after surgery, 6-12 weeks, 6 and 12 months after initial admission). Genetic test results are communicated 6-12 weeks after initial admission to the clinic. DISCUSSION: We created optimal conditions for investigation of the psychosocial impact of prognostic genetic testing. This study will provide information on the course of disease and psychosocial outcomes after prognostic genetic testing. We expect that empirical data from our study will give a scientific basis for medico-ethical considerations. PMID- 27386848 TI - Antibacterial and antibiotic-resistance modifying activity of the extracts and compounds from Nauclea pobeguinii against Gram-negative multi-drug resistant phenotypes. AB - BACKGROUND: Multi-drug resistance of Gram-negative bacteria constitutes a major obstacle in the antibacterial fight worldwide. The discovery of new and effective antimicrobials and/or resistance modulators is necessary to combat the spread of resistance or to reverse the multi-drug resistance. In this study, we investigated the antibacterial and antibiotic-resistance modifying activities against 29 Gram-negative bacteria including multi-drug resistant (MDR) phenotypes of the methanol extracts from Nauclea pobeguiinii leaves (NPL), Nauclea pobeguiinii bark (NPB) and six compounds from the bark extract, identified as 3 acetoxy-11-oxo-urs-12-ene (1), p-coumaric acid (2), citric acid trimethyl ester (3), resveratrol (4), resveratrol beta- D -glucopyranoside (5) and strictosamide (6). METHODS: The broth microdilution method was used to determine the minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) of crude extracts and compounds as well as the antibiotic-resistance modifying effects of MPB and 4. RESULTS: MIC determinations indicate values ranging from 32 1024 MUg/mL for NPB and NPL on 89.7 % and 69.0 % of the tested bacterial strains respectively. MIC values below 100 MUg/mL were obtained with NPB against Escherichia coli ATCC10536, AG100 and Enterobacter aerogenes CM64 strains. The lowest MIC value for crude extracts of 32 MUg/mL was obtained with NPB against E. coli ATCC10536. Compound 4 was active all tested bacteria, whilst 1, 3 and 6 displayed weak and selective inhibitory effects. The corresponding MIC value (16 MUg/mL) was obtained with 4 against Klebsiella pneumoniae KP55 strain. Synergistic effects of the combination of NPB with chloramphenicol (CHL), kanamycin (KAN) as well as that of compound 4 with streptomycin (STR) and ciprofloxacin (CIP) were observed. CONCLUSION: The present study provides information on the possible use of Nauclea pobeguinii and compound 4 in the control of Gram-negative bacterial infections including MDR phenotypes. It also indicates that NPB and 4 can be used as naturally occurring antibiotic-resistance modulators to tackle MDR bacteria. PMID- 27386850 TI - Retraction Note: Efficacy and safety of atypical antipsychotic drug treatment for dementia: a systematic review and meta-analysis. PMID- 27386851 TI - Hemoglobin A1c and Race: Should Therapeutic Targets and Diagnostic Cutoffs Differ among Racial Groups? PMID- 27386849 TI - Excessive visit-to-visit glycemic variability independently deteriorates the progression of endothelial and renal dysfunction in patients with type 2 diabetes mellitus. AB - BACKGROUND: Glycemic variability (GV) creates challenges to glycemic control and may be an independent marker for unfavorable outcome in management of patients with diabetes. This study was designed to investigate the effect of excessive visit-to-visit GV on the progression of endothelial and renal dysfunction in patients with type 2 diabetes mellitus (T2DM). METHODS: Two hundred and thirty nine patients with T2DM, who were recruited from outpatient, completed 48-month follow-up visit. Visit-to-visit GV was calculated by the standard deviation (SD) and coefficient of variation (CV) of serially measured HbA1c and fasting plasma glucose (FPG). Endothelial and renal function was assessed at baseline and end of follow-up. RESULTS: At end of follow-up, brachial flow-mediated dilation (FMD), nitric oxide (NO), creatinine-based estimated glomeruar filtration rate (eGFR Cr), and cystatin C-based estimated glomeruar filtration rate (eGFR-Cys C) increased, and endothelin-1 and urine albumin/creatinine ratio (ACR) declined as compared with baseline in overall (P < 0.05). The increment of FMD, NO, eGFR-Cr, and eGFR-Cys C and the decrement of endothelin-1 and ACR in first tertile group were significantly greater than those in third tertile group classified by tertile of either SD of HbA1c or SD of FPG. Change percentage of FMD, NO, eGFR Cr, and eGFR-Cys C were positively, and change percentage of endothelin-1 and ACR were negatively correlated with SDs of HbA1c and FPG, and CVs of HbA1c FPG (P < 0.01, respectively). After adjusted for mean HbA1c, mean FPG, baseline demographic, and clinical characteristics, SD of HbA1c and SD of FPG were always statistically correlated with change percentage of FMD, NO, endothelin-1, ACR, eGFR-Cr, and eGFR-Cys C. CONCLUSION: Excessive visit-to-visit GV independently deteriorates the progression of endothelial and renal dysfunction in patients with T2DM. PMID- 27386853 TI - Chemical shift assignments of the homodimer protein SP_0782 (7-79) from Streptococcus pneumoniae. AB - The protein SP_0782 from Streptococcus pneumonia is a small homodimeric protein that belongs to a protein family containing representative members with single stranded DNA (ssDNA) binding functions. The ssDNA binding of the homolog YdbC from Lactococcus lactis was previously characterized when bound to a 20-mer of pyridine-rich ssDNA, sharing an overall similar structural fold with the human transcription coactivator PC4. We report that SP_0782 exhibits distinct differences in ssDNA binding properties from YdbC as revealed by NMR titration experiments. Unlike the binding of the ssDNA dT19G1 to PC4 and YdbC, SP_0782 resulted in aggregation. In addition, SP_0782 exhibits favorable binding to shorter ssDNA such as dT6. The reason is unclear, and the SP_0782 structure function relationship remains to be elucidated. Here, we report the complete (1)H, (13)C, and (15)N backbone and side chain NMR assignments of SP_0782, residues 7-79. PMID- 27386854 TI - (1)H, (13)C and (15)N backbone resonance assignment for the 40.5 kDa catalytic domain of Ubiquitin Specific Protease 7 (USP7). AB - The deubiquitinase Ubiquitin Specific Protease 7 (USP7) is part of the regulatory cascade of proteins that modulates the activity of the tumor suppressor protein p53. Deubiquitination of its target Murine Double Minute 2 (MDM2) leads to increased proteosomal degradation of p53. Consequently, USP7 has emerged as an attractive oncology target because its inhibition stabilizes p53, thereby promoting p53-dependent apoptosis in cancer cells. Here we report the backbone resonance assignment for the 40.5 kDa catalytic domain of USP7. PMID- 27386852 TI - Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith-Magenis syndrome with evident peripheral neuropathy. AB - Hereditary neuropathy with liability to pressure palsies (HNPP) and Smith-Magenis syndrome (SMS) are genomic disorders associated with deletion copy number variants involving chromosome 17p12 and 17p11.2, respectively. Nonallelic homologous recombination (NAHR)-mediated recurrent deletions are responsible for the majority of HNPP and SMS cases; the rearrangement products encompass the key dosage-sensitive genes PMP22 and RAI1, respectively, and result in haploinsufficiency for these genes. Less frequently, nonrecurrent genomic rearrangements occur at this locus. Contiguous gene duplications encompassing both PMP22 and RAI1, i.e., PMP22-RAI1 duplications, have been investigated, and replication-based mechanisms rather than NAHR have been proposed for these rearrangements. In the current study, we report molecular and clinical characterizations of six subjects with the reciprocal phenomenon of deletions spanning both genes, i.e., PMP22-RAI1 deletions. Molecular studies utilizing high resolution array comparative genomic hybridization and breakpoint junction sequencing identified mutational signatures that were suggestive of replication based mechanisms. Systematic clinical studies revealed features consistent with SMS, including features of intellectual disability, speech and gross motor delays, behavioral problems and ocular abnormalities. Five out of six subjects presented clinical signs and/or objective electrophysiologic studies of peripheral neuropathy. Clinical profiling may improve the clinical management of this unique group of subjects, as the peripheral neuropathy can be more severe or of earlier onset as compared to SMS patients having the common recurrent deletion. Moreover, the current study, in combination with the previous report of PMP22-RAI1 duplications, contributes to the understanding of rare complex phenotypes involving multiple dosage-sensitive genes from a genetic mechanistic standpoint. PMID- 27386855 TI - Resonance assignments of a VapC family toxin from Clostridium thermocellum. AB - Toxin-antitoxin (TA) systems widely exist in bacterial plasmids, phages, and chromosomes and play important roles in growth persistence and host-pathogen interaction. Virulence associated protein BC (VapBC) family TAs are the most abundant TAs in bacteria and many pathogens contain a large number of vapBC loci in the genome which have been extensively studied. Clostridium thermocellum, a cellulolytic anaerobic gram-positive bacterium with promising applications in biofuel production, also contains a VapBC TA in the genome. Despite the structures of several VapBC family TAs have been determined, the toxin and anti toxin components of C. thermocellum VapBC have very low sequence identity to the proteins in PDB. Therefore, the structure and functional mechanism of this TA is largely unknown. Here we reported the NMR resonance assignments of the VapC toxin from C. thermocellum as a basis for further structural and functional studies. PMID- 27386856 TI - [Not Available]. PMID- 27386857 TI - [Not Available]. PMID- 27386858 TI - Comparison of the Risk of Gastrointestinal Bleeding among Different Statin Exposures with Concomitant Administration of Warfarin: Electronic Health Record Based Retrospective Cohort Study. AB - BACKGROUND AND OBJECTIVE: Patients who should be treated with both warfarin and a statin are frequently seen in vascular clinics. The risk for bleeding and potential drug interactions should be considered when prescribing both medications together. This study aimed to compare the risk for gastrointestinal bleeding among different statin exposures with concomitant administration of warfarin. MATERIALS AND METHODS: This is a single-hospital retrospective cohort study. We included patients who were concomitantly exposed to one of four statins (pravastatin, simvastatin, atorvastatin, and rosuvastatin) and warfarin for up to 2 years (730 days). The observation period ended when a gastrointestinal bleeding event occurred or the observation was censored. Within-class comparisons were used, and 1:1 matching using a propensity score was performed for comparisons between each statin and all of the other statins. Kaplan-Meier analyses with log rank tests and Cox proportional hazard regression analyses were conducted to determine associations with the risk of gastrointestinal bleeding. RESULTS: Data were analyzed for 1,686 patients who were concomitantly administered a statin and warfarin. Log-rank tests for the gastrointestinal bleeding-free survival rate showed that the risk for gastrointestinal bleeding was significantly lower in the pravastatin group (p = 0.0499) and higher in the rosuvastatin group (p = 0.009). In the Cox proportional hazard regression analysis, the hazard ratio of 5.394 for gastrointestinal bleeding based on statin exposure in the rosuvastatin group was significant (95% confidence interval, 1.168-24.916). CONCLUSIONS: There was a relatively high risk of gastrointestinal bleeding with rosuvastatin when administered concomitantly with warfarin. PMID- 27386859 TI - Association between Subclinical Malaria Infection and Inflammatory Host Response in a Pre-Elimination Setting. AB - BACKGROUND: Subclinical infections in endemic areas of Southeast Asia sustain malaria transmission. These asymptomatic infections might sustain immunity against clinical malaria and have been considered benign for the host, but if they are associated with chronic low-grade inflammation this could be harmful. We conducted a case-control study to explore the association between subclinical malaria and C-reactive protein (CRP), an established biomarker of inflammation. METHODS: Blood samples from asymptomatic villagers in Pailin, Western Cambodia were tested for malaria by high-volume ultra-sensitive polymerase chain reaction (uPCR) to determine the Plasmodium species. Plasma CRP concentration was measured in 328 individuals with parasitaemia (cases) and compared with: i) the same individual's value at the first time point when they had no detectable parasites (n = 282); and ii) age- sex- and village-matched controls (n = 328) free of Plasmodium infection. Plasma CRP concentrations were compared against thresholds of 3mg/L and 10mg/L. Subgroup analysis was carried out for cases with P vivax and P falciparum mono-infections. RESULTS: Median plasma CRP level for all samples was 0.59mg/L (interquartile range: 0.24-1.64mg/L). CRP concentrations were higher in parasitaemic individuals compared with same-person-controls (p = 0.050); and matched-controls (p = 0.025). 4.9% of samples had CRP concentrations above 10mg/L and 14.6% were above 3mg/L. Cases were more likely to have plasma CRP concentrations above these thresholds than age/sex matched controls, odds ratio 3.5 (95%CI 1.5-9.8) and 1.8 (95%CI 1.1-2.9), respectively. Amongst cases, parasite density and CRP were positively correlated (p<0.001), an association that remained significant when controlling for age and fever. Individuals with P.vivax mono-infections had the highest plasma CRP concentrations with the greatest association with parasitaemia. DISCUSSION: In this setting persistent malaria infections in asymptomatic individuals were associated with moderately elevated plasma CRP concentrations; chiefly evident in cases with P.vivax mono infections. As well as interrupting malaria transmission within the community, treatment of asymptomatic malaria infections, in particular radical cure of vivax malaria, may benefit the health of infected individuals. PMID- 27386860 TI - Economic interventions to improve population health: a scoping study of systematic reviews. AB - BACKGROUND: Recognizing the close relationship between poverty and health, national program managers, policy-makers and donors are increasingly including economic interventions as part of their core strategies to improve population health. However, there is often confusion among stakeholders about the definitions and operational differences between distinct types of economic interventions and financial instruments, which can lead to important differences in interpretation and expectations. METHODS: We conducted a scoping study to define and clarify concepts underlying key economic interventions - price interventions (taxes and subsidies), income transfer programs, incentive programs, livelihood support programs and health-related financial services - and map the evidence currently available from systematic reviews. RESULTS: We identified 195 systematic reviews on economic interventions published between 2005 and July 2015. Overall, there was an increase in the number of reviews published after 2010. The majority of reviews focused on price interventions, income transfer programs and incentive programs, with much less evidence available from systematic reviews on livelihood support programs and health related financial services. We also identified a lack of evidence on: health outcomes in low income countries; unintended or perverse outcomes; implementation challenges; scalability and cost-effectiveness of economic interventions. CONCLUSIONS: We conclude that while more research is clearly needed to assess suitability and effectiveness of economic interventions in different contexts, before interventions are tested and further systematic reviews conducted, a consistent and accurate understanding of the fundamental differences in terminology and approaches is essential among researchers, public health policy makers and program planners. PMID- 27386861 TI - Insights into How Longicorn Beetle Larvae Determine the Timing of Metamorphosis: Starvation-Induced Mechanism Revisited. AB - Larvae of holometabolous insects must determine the timing of their metamorphosis. How they determine this timing has only been studied in detail for a few insect species. In a few species of Coleoptera, starvation is known to be a cue for metamorphosis, leading to the formation of smaller adults (starvation induced pupation, SiP). We investigated the occurrence of SiP in the beetle Psacothea hilaris. When P. hilaris larvae were starved late in the feeding phase of the last (5th) instar, they exhibited typical SiP characterized by constancy of the time from food deprivation to pupation (TTP) irrespective of the body weight upon food deprivation or the length of prior feeding. In contrast, when larvae were starved early in the feeding phase, TTP decreased by roughly 1 day as the feeding became 1 day longer. The change in the response to starvation was estimated to occur on day 5.9 in the last instar. A series of refeeding experiments suggested that whereas SiP occurred readily in the larvae starved in the late feeding phase, activation of SiP was suspended until day 5.9 in the larvae starved early in the feeding phase. When P. hilaris larvae were fed continuously, they eventually ceased feeding spontaneously and pupated. The time length between spontaneous cessation of feeding and pupation was approximately equal to the TTP in SiP. This suggests that the same mechanism was activated by food deprivation in the late feeding phase and by spontaneous cessation of ad libitum feeding. PMID- 27386862 TI - Post-Transcriptional Regulation of KLF4 by High-Risk Human Papillomaviruses Is Necessary for the Differentiation-Dependent Viral Life Cycle. AB - Human papillomaviruses (HPVs) are epithelial tropic viruses that link their productive life cycles to the differentiation of infected host keratinocytes. A subset of the over 200 HPV types, referred to as high-risk, are the causative agents of most anogenital malignancies. HPVs infect cells in the basal layer, but restrict viral genome amplification, late gene expression, and capsid assembly to highly differentiated cells that are active in the cell cycle. In this study, we demonstrate that HPV proteins regulate the expression and activities of a critical cellular transcription factor, KLF4, through post-transcriptional and post-translational mechanisms. Our studies show that KLF4 regulates differentiation as well as cell cycle progression, and binds to sequences in the upstream regulatory region (URR) to regulate viral transcription in cooperation with Blimp1. KLF4 levels are increased in HPV-positive cells through a post transcriptional mechanism involving E7-mediated suppression of cellular miR-145, as well as at the post-translational level by E6-directed inhibition of its sumoylation and phosphorylation. The alterations in KLF4 levels and functions results in activation and suppression of a subset of KLF4 target genes, including TCHHL1, VIM, ACTN1, and POT1, that is distinct from that seen in normal keratinocytes. Knockdown of KLF4 with shRNAs in cells that maintain HPV episomes blocked genome amplification and abolished late gene expression upon differentiation. While KLF4 is indispensable for the proliferation and differentiation of normal keratinocytes, it is necessary only for differentiation associated functions of HPV-positive keratinocytes. Increases in KLF4 levels alone do not appear to be sufficient to explain the effects on proliferation and differentiation of HPV-positive cells indicating that additional modifications are important. KLF4 has also been shown to be a critical regulator of lytic Epstein Barr virus (EBV) replication underscoring the importance of this cellular transcription factor in the life cycles of multiple human cancer viruses. PMID- 27386863 TI - Telomere Length and the Cancer-Atherosclerosis Trade-Off. AB - Modern humans, the longest-living terrestrial mammals, display short telomeres and repressed telomerase activity in somatic tissues compared with most short living small mammals. The dual trait of short telomeres and repressed telomerase might render humans relatively resistant to cancer compared with short-living small mammals. However, the trade-off for cancer resistance is ostensibly increased age-related degenerative diseases, principally in the form of atherosclerosis. In this communication, we discuss (a) the genetics of human telomere length, a highly heritable complex trait that is influenced by genetic ancestry, sex, and paternal age at conception, (b) how cancer might have played a role in the evolution of telomere biology across mammals, (c) evidence that in modern humans telomere length is a determinant (rather than only a biomarker) of cancer and atherosclerosis, and (d) the potential influence of relatively recent evolutionary forces in fashioning the variation in telomere length across and within populations, and their likely lasting impact on major diseases in humans. Finally, we propose venues for future research on human telomere genetics in the context of its potential role in shaping the modern human lifespan. PMID- 27386864 TI - Carbon ion therapy (C12) for high-grade malignant salivary gland tumors (MSGTs) of the head and neck: do non-ACCs profit from dose escalation? AB - PURPOSE: To evaluate the use of high-dose radiotherapy using carbon ions (C12) on non-adenoid cystic malignant salivary gland tumors (MSGT). PATIENTS AND METHODS: Between 2009 and 2013, patients with biopsy-proven non-ACC MSGT histologies of the head and neck received a combined regimen of IMRT plus C12 boost. Treatment toxicity (CTC v3), response (RECIST 1.1), control and survival rates were retrospectively analyzed. RESULTS: 40 patients with pathologically confirmed non ACC MSGT (T4: 45 %; N+: 40 %; gross residual: 58 %; mucoepidermoid carcinoma (MEC): 45 %; adenocarcinoma: 20 %) were treated with a median of 74 GyE (80 Gy BED). Chemoradiation was given in 5 patients with MEC. Grade III acute toxicity was observed in up to 15 % (mucositis, dermatitis, dysphagia), no higher-grade late toxicity occurred to date. At a follow-up of 25.5 months, LC, and PFS at 2 and 3 years are 81.5 % (LC) and 66.8 % (PFS), OS at 2 and 3 years is 83.6 % and 72.8 %. Most frequent site of disease progression was distant metastasis. Histologic subtype correlated with LC and PFS. Resection status (gross vs microscopic disease) had no significant effect on LC, PFS, or OS. CONCLUSION: The treatment is well tolerated, no higher grade late effects were observed. Considering the negative pre-selection, LC, PFS and OS are promising. While histology and site of origin significantly influenced control and survival rates, resection status did not, potentially due to the effect of dose escalation. PMID- 27386865 TI - Effect of Perioperative Dexamethasone and Different NSAIDs on Anastomotic Leak Risk: A Propensity Score Analysis. AB - BACKGROUND: Perioperative use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with risk of anastomotic leak (AL). However, concomitant use of other drugs could infer a bias in risk assessment. Thus, we aimed to interrogate the risk of AL associated with NSAIDs and steroids used perioperatively. METHODS: This study includes a consecutive series of patients having surgery involving an intestinal anastomosis from Jan 2007 to Dec 2009. Data records included demographic, perioperative, and surgical characteristics; AL rates; and use of NSAIDs and steroids. Risk of leak were estimated using unadjusted and multivariable (propensity score)-adjusted logistic regression models and reported as odds ratios (ORs). RESULTS: A total of 376 patients underwent 428 operations of which 67 (15.7 %) had AL. With no medication receivers as reference, the OR for leak when adjusted for age, sex, and propensity score was 1.07 (p = 0.92) for ketorolac, 1.63 (p = 0.31) for diclofenac and 0.41 (p = 0.19) for dexamethasone. Risk was increased for malignancy (OR 1.88, p = 0.023), use of a vasopressor (OR 2.52, p = 0.007), blood transfusions (OR 1.93, p = 0.026), and regular use of steroids (OR 7.57, p = 0.009). CONCLUSIONS: Other factors than perioperative drugs are crucial for risk of AL. Perioperative dexamethasone was associated with a nonsignificant reduced risk of AL. PMID- 27386866 TI - Injury Characteristics and Outcomes in Elderly Trauma Patients in Sub-Saharan Africa. AB - BACKGROUND: Traumatic injury in the elderly is an emerging global problem with an associated increase in morbidity and mortality. This study sought to describe the epidemiology of elderly injury and outcomes in sub-Saharan Africa. METHODS: We conducted a retrospective analysis of adult patients (>= 18 years) with traumatic injuries presenting to the Kamuzu Central Hospital (KCH) in Lilongwe, Malawi, over 5 years (2009-2013). Elderly patients were defined as adults aged >=65 years and compared to adults aged 18-44 and 45-64 years. We used propensity score matching and logistic regression to compare the odds of mortality between age groups using the youngest age group as the reference. RESULTS: 42,816 Adult patients with traumatic injuries presented to KCH during the study period. 1253 patients (2.9 %) were aged >=65 years with a male preponderance (77.4 %). Injuries occurred more often at home as age increased (25.3, 29.5, 41.1 %, p < 0.001) and falls were more common (14.1, 23.8, 36.3 %, p < 0.001) for elderly patients. Elderly age was associated with a higher proportion of hospital admissions (10.6, 21.3, 35.2 %, p < 0.001). Upon propensity score matching and logistic regression analysis, the odds ratio of mortality for patients aged >=65 was 3.15 (95 % CI 1.45, 6.82, p = 0.0037) compared to the youngest age group (18 44 years). CONCLUSIONS: Elderly trauma in a resource-poor area in sub-Saharan Africa is associated with a significant increase in hospital admissions and mortality. Significant improvements in trauma systems, pre-hospital care, and hospital capacity for older, critically ill patients are imperative. PMID- 27386867 TI - Integrative Health: Implications from a Report That Medical Errors Are the USA's Third Leading Cause of Death. PMID- 27386869 TI - US has worst traffic accident death rate among high income countries. PMID- 27386868 TI - Dynamic corset versus three-point brace in the treatment of osteoporotic compression fractures of the thoracic and lumbar spine: a prospective, comparative study. AB - BACKGROUND: The three-point orthosis is the most commonly used brace in the conservative treatment of osteoporotic vertebral fractures. The Spinomed(r) dynamic orthosis represents an alternative. AIMS: We compared efficacy and safety of these two types of brace in treating osteoporotic vertebral fractures. METHODS: One hundred forty patients, aged 65-93 years, sustaining osteoporotic vertebral fracture were consecutively recruited and divided into two groups, and treated with either three-point orthosis or dynamic corset. Patients were evaluated with Visual Analogue Scale, Oswestry Low Back Pain Disability Questionnaire, and measurement of forced expiratory volume in the first second. Regional kyphosis angle, Delmas Index, and height of the fractured vertebral body were also measured on full-spine X-rays. Follow-up intervals were 1, 3, and 6 months after trauma. The complications encountered during the 6-month follow-up were recorded. RESULTS: At the 3- and 6-month follow-ups, there was a significant difference (p < 0.05) in pain, disability, and respiration in favor of the dynamic orthosis group. At 6-month follow-up, there was no significant difference (p > 0.05) in all the radiological parameters between groups. Complications were reported for 28 patients in the three-point orthosis group, and for eight patients in the dynamic corset group (p < 0.05). DISCUSSION: Biofeedback activation of back muscles is probably a key factor in improving functional outcome with dynamic orthosis. CONCLUSIONS: Compared to three-point orthosis, patients treated with dynamic orthosis had a greater reduction in pain and a greater improvement in quality of life and respiratory function, with equal effectiveness in stabilizing the fracture, and fewer complications. PMID- 27386870 TI - Dopamine in plasma - a biomarker for myofascial TMD pain? AB - BACKGROUND: Dopaminergic pathways could be involved in the pathophysiology of myofascial temporomandibular disorders (M-TMD). This study investigated plasma levels of dopamine and serotonin (5-HT) in patients with M-TMD and in healthy subjects. METHODS: Fifteen patients with M-TMD and 15 age- and sex-matched healthy subjects participated. The patients had received an M-TMD diagnosis according to the Research Diagnostic Criteria for TMD. Perceived mental stress, pain intensity (0-100-mm visual analogue scale), and pressure pain thresholds (PPT, kPa) over the masseter muscles were assessed; a venous blood sample was taken. RESULTS: Dopamine in plasma differed significantly between patients with M TMD (4.98 +/- 2.55 nM) and healthy controls (2.73 +/- 1.24 nM; P < 0.01). No significant difference in plasma 5-HT was observed between the groups (P = 0.75). Patients reported significantly higher pain intensities (P < 0.001) and had lower PPTs (P < 0.01) compared with the healthy controls. Importantly, dopamine in plasma correlated significantly with present pain intensity (r = 0.53, n = 14, P < 0.05) and perceived mental stress (r = 0.34, n = 28, P < 0.05). CONCLUSIONS: The results suggest that peripheral dopamine might be involved in modulating peripheral pain. This finding, in addition to reports in other studies, suggests that dopaminergic pathways could be implicated in the pathophysiology of M-TMD but also in other chronic pain conditions. More research is warranted to elucidate the role of peripheral dopamine in the pathophysiology of chronic pain. PMID- 27386871 TI - Measurement of Ether Phospholipids in Human Plasma with HPLC-ELSD and LC/ESI-MS After Hydrolysis of Plasma with Phospholipase A1. AB - Ethanolamine ether phospholipid (eEtnGpl) and choline ether phospholipid (eChoGpl) are present in human plasma or serum, but the relative concentration of the ether phospholipids in plasma is very low as compared to those in other tissues. Nowadays, measurement of ether phospholipids in plasma depends on tandem mass spectrometry (LC/MS/MS), but a system for LC/MS/MS is generally too expensive for usual clinical laboratories. Treatment of plasma with phospholipase A1 (PLA1) causes complete hydrolysis of diacylphospholipids, but ether phospholipids remain intact. After the treatment of plasma with PLA1, both eEtnGpl and eChoGpl are detected as independent peaks by high-performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD). The same sample used for HPLC-ELSD can be applied to detect eEtnGpl and eChoGpl with electrospray ionization mass spectrometry. Presence of alkylacylphospholipids in both eChoGpl and eEtnGpl in human plasma was indicated by sequential hydrolysis of plasma with PLA1 and hydrochloric acid. PMID- 27386873 TI - [Not Available]. PMID- 27386872 TI - Neuroprotective Fatty Acids from the Stem Bark of Sorbus commixta. AB - Phytochemical investigation of the bark from the stems of Sorbus commixta led to the isolation and characterization of a new fatty acid, sorcomic acid (1), along with nine known analogues (2-10). The structure of the new compound (1) was determined through NMR ((1)H and (13)C NMR, HSQC, HMBC, and NOESY), MS, and specific optical rotation. The known compounds (2-10) were identified by comparison of their spectroscopic data with those in the literature. The biological activities of all the isolated compounds (1-10) were evaluated: compounds 1, 5, and 7 potently induced NGF secretion from C6 glioma cells (233.40 +/- 12.82, 194.40 +/- 8.05, and 185.74 +/- 10.25 %, respectively) and compound 10 reduced NO levels with an IC50 value of 71.25 MUM in murine microglia BV2 cells stimulated by LPS. PMID- 27386875 TI - Repair of Neurological Function in Response to FK506 Through CaN/NFATc1 Pathway Following Traumatic Brain Injury in Rats. AB - Tacrolimus (FK506), an immunophilin ligand, has been widely shown to be neuroprotective in a posttraumatic period. The nuclear factor of activated T cells (NFATc1) pathway plays an important role in regenerating neurological function following traumatic brain injury (TBI), but the precise mechanism underlying FK506-induced repair of neurological functions remains unclear. In the present study, a total of 210 SD rats were enrolled and randomly divided into sham group, TBI group and FK506 group. The rats in the TBI and FK506 groups were inflicted with moderate TBI left lateral fluid percussion impact. A modified neurological severity score (mNSS) system was used to evaluate the severity of effects on nerve function. mNSS levels were significantly lower in the FK506 group than in the TBI group. The zaccumulation of cerebral water content was lower, cerebral Aquaporin 4 (AQP4) mRNA level was lower, the number of growth associated protein-43 (GAP-43)-positive cells was higher, and the distribution of vesicles containing excitatory neurotransmitters was altered in the injured cortex in the FK506 group. Moreover, the cortical mRNA and serum protein expression levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were decreased in FK506 group, especially at 6 h and at 1 day after TBI. At days 1-28 after TBI, the expression of cleaved-caspase 3, which indicates apoptosis, was lower in the FK506 group than in the TBI group. Mechanistically, FK506 significantly down-regulated the mRNA and protein levels of calcium-regulated phosphatase (calcineurin, CaN) and inhibited the activation of NFATc1. These results demonstrate that FK506 relieved inflammatory responses by regulating the NFATc1 signaling pathway and promoting the synaptic reconstruction of neurons and glial cells by regulating cell apoptosis, thereby facilitated improvements in neurological function. PMID- 27386874 TI - Neuroprotective Effect of Hydrogen-Rich Saline in Global Cerebral Ischemia/Reperfusion Rats: Up-Regulated Tregs and Down-Regulated miR-21, miR-210 and NF-kappaB Expression. AB - Recently, it has been suggested that molecular hydrogen (H2) can selectively reduce the levels of hydroxyl radicals (.OH), and ameliorate oxidative and inflammatory injuries to organs in global cerebral ischemia reperfusion models. Global cerebral ischemia/reperfusion (I/R) can induce a sudden activation of inflammatory cytokines and later influence the systemic immunoreactivity which may contribute to a worse outcome. Regulatory T cells (Tregs) are involved in several pathological aspects of cerebral I/R. In addition, miRNA took part in the processes of cellular response to hypoxia. Since the expression of a specific set of miRNA called "hypoxamirs" is upregulated by hypoxia. Therefore, the aim of this study was to analyze the effect of HRS on I/R inducing cerebral damage, Tregs, and specific miRNA. Our results showed that rats undergone global cerebral I/R and treated with HRS have milder injury than I/R animals without HRS treatment. miR-210 expression in the hippocampus of the I/R group at 6, 24 and 96 h after reperfusion was significantly increased at each time point, while its expression in the group treated with HRS was significantly decreased. In addition, Tregs number in group I/R was decreased at each time points, while its number in the group treated with HRS was increased at 24 and 96 h after reperfusion. We focus on the relationship among Tregs, TGF-beta1, TNF-alpha and NF-kappaB at 24 h, and we found that there is a high correlation among them. Therefore, our results indicated that the brain resuscitation mechanism in the HRS-treated rats may be related with the effect of upregulating the number of Treg cells. PMID- 27386876 TI - In vivo micronucleus screening in zebrafish by flow cytometry. AB - Micronucleus (MN) assay is extensively used to biomonitor aneuploidy and clastogenicity of genotoxic compounds. However, the suitability of this assay for early life stages of model fish species is still poorly documented. In this study, the determination of MN using flow cytometry was successfully applied for the first time to zebrafish (Danio rerio) larvae. Mitomycin C (MMC), etoposide (ETO), cyclophosphamide, demecolcine (COL), benzo[a]pyrene (BP) and dibenzo[def,p]chrysene (DBC) were selected as model genotoxicants. The method was first confirmed in human HepG2 liver cells and then applied in vivo on isolated cells from exposed 4 days post fertilisation zebrafish larvae. All tested compounds induced MN formation. The flow cytometry results were validated by a strong correlation with results from a standard MN microscopy analysis (P = 0.002). Moreover, flow cytometry analysis enabled the detection of an up to 3.7 fold increase of hypodiploidy in zebrafish exposed to MMC, COL, BP or DBC. MMC, COL and DBC induced more than a 2-fold MN increase by flow cytometry and were therefore considered as the most suitable positive controls for in vivo zebrafish MN determination. These findings make important contribution by proposing a new reliable and sensitive method for using zebrafish as a model for genotoxicity monitoring. PMID- 27386877 TI - Environmental concentration of carbamazepine accelerates fish embryonic development and disturbs larvae behavior. AB - Environmental pollution caused by pharmaceuticals has been recognized as a major threat to the aquatic ecosystems. Carbamazepine, as the widely prescribed antiepileptic drug, has been frequently detected in the aquatic environment and has created concerns about its potential impacts in the aquatic organisms. The effects of carbamazepine on zebrafish embryos were studied by examining their phenotype, behavior and molecular responses. The results showed that carbamazepine disturbed the normal growth and development of exposed zebrafish embryos and larvae. Upon exposure to carbamazepine at 1 MUg/L, the hatching rate, body length, swim bladder appearance and yolk sac absorption rate were significantly increased. Embryos in treatment groups were more sensitive to touch and light stimulation. At molecular level, exposure to an environmentally relevant concentration (1 MUg/L) of carbamazepine disturbed the expression pattern of neural-related genes of zebrafish embryos and larvae. This study suggests that the exposure of fish embryo to antiepileptic drugs, at environmentally relevant concentrations, affects their early development and impairs their behavior. Such impacts may have future repercussions by affecting fish population structure. PMID- 27386879 TI - Sexist Humor and Rape Proclivity: The Moderating Role of Joke Teller Gender and Severity of Sexual Assault. AB - Three experiments examined the effect of sexist humor on men's self-reported rape proclivity (RP). Pilot study demonstrated that people differentiate the five rape scenarios of Bohner et al.'s. RP Scale based on the degree of physical violence perpetrated against the victim. Experiment 1 demonstrated that men higher in hostile sexism report greater RP upon exposure to sexist jokes when a woman (vs. a man) delivers them, and that this effect is limited to rape scenarios depicting a moderate versus a high level of physical violence. Experiment 2 further demonstrated that the relationship between hostile sexism and rape proclivity in response to a moderately violent rape scenario after exposure to sexist humor generalizes beyond women in the immediate humor context to women as a whole. PMID- 27386878 TI - Influence of chloride on the chronic toxicity of sodium nitrate to Ceriodaphnia dubia and Hyalella azteca. AB - While it has been well established that increasing chloride concentration in water reduces the toxicity of nitrite to freshwater species, little work has been done to investigate the effect of chloride on nitrate toxicity. We conducted acute and chronic nitrate (as sodium nitrate) toxicity tests with the cladoceran Ceriodaphnia dubia and the amphipod Hyalella azteca (chronic tests only) over a range of chloride concentrations spanning natural chloride levels found in surface waters representative of watersheds of the Great Lakes Region. Chronic nitrate toxicity test results with both crustaceans were variable, with H. azteca appearing to be one of the more sensitive invertebrate species tested and C. dubia being less sensitive. While the variability in results for H. azteca were to an extent related to chloride concentration in test water that was distinctly not the case for C. dubia. We concluded that the chloride dependent toxicity of nitrate is not universal among freshwater crustaceans. An additional sodium chloride chronic toxicity test with the US Lab strain of H. azteca in the present study suggested that when present as predominantly sodium chloride and with relatively low concentrations of other ions, there is a narrow range of chloride concentrations over which this strain is most fit, and within which toxicity test data are reliable. PMID- 27386880 TI - "I Fear I'm a Checkbox": College and University Victim Advocates' Perspectives of Campus Rape Reforms. AB - This study explores campus-based victim advocates' perspectives on the process of implementing campus rape reforms mandated by federal policy. Interviews with 14 victim advocates and sexual assault prevention specialists were analyzed qualitatively using thematic analysis techniques. Participants described an increased focus on compliance as a means of managing the liability risks associated with inadequate policy implementation. These shifts toward compliance not only increased the motivation to accomplish reform but also limited those reforms by narrowing the focus. Participants described how narrow compliance resulted in decisions that may actually harm victims. Suggestions for improving policy and the implementation process are discussed. PMID- 27386881 TI - Effect of sous vide processing on physicochemical, ultrastructural, microbial and sensory changes in vacuum packaged chicken sausages. AB - The processing of sous vide chicken sausages was optimized under vacuum packaging condition and cooking at 100 C for 30 min (SV30), 60 min (SV60) and 120 min (SV120) and compared with aerobically cooked control at 100 C for 30 min. Sous vide processing of chicken sausages (SV30) produced higher (p < 0.05) cooking yield, Hunterlab a* values and sensory attributes without affecting proximate composition and shear force values relative to control. The sodium dodecyl sulphate-polyacrylamide gel electrophoresis and scanning electron microscopy results revealed no significant changes in protein quality and emulsion ultra structure due to SV30 processing relative to control sausages. Sous vide processing of chicken sausages enriched with rosemary diterpene phenols retained the freshness and quality up to 120 days during storage at 4 +/- 1 C relative to control sausages that were spoiled on 20th day. Lipid oxidation and microbial growth remained below the spoilage levels for all the SV-processed sausages throughout the storage and addition of rosemary diterpene mixture at 0.02% v/w reduced the microbial growth and improved (p < 0.05) the sensory attributes. Our results demonstrate that sous vide processing minimizes lipid oxidation and microbial growth of chicken sausages with improved product quality and shelf-life at 4 +/- 1 C. PMID- 27386882 TI - Effect of process technology on the nutritional, functional, and physical quality of grapefruit powder. AB - The health properties of fruit are widely known. Powdered fruit may be a practical format to be offered to the consumer. Nevertheless, the process used to obtain the powder must ensure the maximum retention of the bioactive compounds and the functional value of the fruit while retaining adequate physical properties. The aim of this study was to compare freeze-drying and spray drying as the drying technologies to obtain grapefruit powder. The obtained results allow freeze-drying to be proposed as a better technology than spray drying in order to obtain a product with a higher content of vitamin C and total carotenoids. Moreover, all of the edible part of the fruit is used in this case, so a greater quantity of healthy compounds is preserved and by-product generation is avoided. Adding about 6 g water, 4 g Arabic gum and 0.6 g bamboo fibre/100 g grapefruit pulp is recommended before freeze-drying. PMID- 27386885 TI - Sexual Violence History and Welfare in Transgender People. AB - This study focuses on sexual violence experiences suffered by Spanish transgender individuals throughout the life span. Using a cross-sectional design, 33 face-to face semi-structured interviews were conducted which included questions regarding the presence and/or absence of sexual violence, the nature of said sexual violence, by whom sexual violences were committed, coping mechanisms used, and certain mental health indicators. Results found a high percentage of transgender individuals to have been victims of sexual violence during childhood, to use avoidance as a coping mechanism for said experiences, as well as the frequent recurrence of experiences of sexual violence, showing victimization processes. In addition, the relationship between said experiences and mental health indicators were observed. This study highlights the importance of and need for addressing sexual violence among this population, and discusses and analyzes possible components of future educative and clinical intervention strategies. PMID- 27386883 TI - Association of pre-ablation level of potential blood markers with atrial fibrillation recurrence after catheter ablation: a meta-analysis. AB - Aims: The meta-analysis was aimed to search for candidate blood markers whose pre ablation level was associated with atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA). Methods and results: A systematic literature search of PubMed, EMBASE, Springer Link, Web of Science, Wiley Cochrane library, and supplemented with Google scholar search engine was performed. Thirty-six studies covering 11 blood markers were qualified for this meta-analysis. Compared with the nonrecurrence group, the recurrence group had increased pre-ablation level of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-pro-BNP), interleukin-6 (IL-6), C-reactive protein, low density lipoprotein (LDL), and tissue inhibitor of metal loproteinase-2 (TIMP-2) [standardized mean difference (95% confidence interval): 0.37 (0.13-0.61), 0.77 (0.40-1.14), 1.25 (0.64-1.87), 0.37 (0.21-0.52), 0.35 (0.10-0.60), 0.24 (0.07-0.42), 0.17 (0.00-0.34), respectively], while no statistical difference of pre-ablation level of white blood cell, total cholesterol, triglyceride, and transforming growth factor-beta1 was found. Subgroup analysis demonstrated that ANP was associated with AF recurrence in participants who had no concomitant structural heart diseases (SHD); however, not in participants who had SHD, C-reactive protein was associated with AF recurrence in Asian studies, whereas not in European studies. Conclusion: Increased pre-ablation level of ANP, BNP, NT-pro-BNP, IL-6, C reactive protein, LDL, and TIMP-2 was associated with greater risk of AF recurrence after RFCA. PMID- 27386886 TI - To Stay in or Leave an Abusive Relationship: Losses and Gains Experienced by Battered Filipino Women. AB - The present study aimed to describe and analyze the losses and gains experienced by battered Filipino women as a result of their decision to stay in or leave an abusive relationship. In-depth, semistructured interviews were conducted with 60 battered women, 30 of the women were still living with their abusive husbands/partners and 30 have left their abusive husbands/partners. Results from the phenomenological data analysis of the qualitative data revealed that the women who stayed in and left their abusive partners experienced both losses and gains. For the women who stayed in an abusive relationship, they lost a sense of self, the opportunity for a better life, peace of mind, psychological well-being, and love for their partners. However, these women had the benefits of having a complete family and a partner to help raise their children. In contrast, despite not having a complete family or a partner to help them raise their children, women who left an abusive relationship gained back their sense of self, peace of mind, freedom, inner strength, and hope. Implications for counseling practice were discussed. PMID- 27386887 TI - Psychological Distress and Revictimization Risk in Youth Victims of Sexual Abuse. AB - Psychological distress, including depression and anxiety, has been associated with increased risk for sexual revictimization in youth who have experienced child sexual abuse. The present study utilized assessment information from treatment seeking youth with histories of sexual abuse to explore specific risk indicators for revictimization-risk taking, social problems, maladaptive cognitions, and posttraumatic stress-that may be indicated by self-reported distress. The relationship between initial levels of distress and change in symptoms over a 12-week course of treatment was also explored. Participants were 101 youth referred to a child-focused therapeutic group for victims of sexual abuse, 65 youth referred to an adolescent-focused group, and their non-offending caregivers. Results revealed that when combined into a distress score, depression and anxiety were associated with delinquent behaviors, interpersonal difficulties, maladaptive cognitions, and posttraumatic stress symptoms for child and adolescent group participants at presentation to treatment. Children exhibited improvement on measures of interpersonal difficulties, maladaptive cognitions, and self-reported posttraumatic stress disorder (PTSD) symptoms. Adolescents exhibited less change over time, with significant improvement on self reported social problems and PTSD only. Higher psychological distress was associated with less improvement in regard to negative expectations of abuse impact for child group participants. The findings suggest that distress indicates the presence of specific revictimization risk indicators, helping to identify targetable symptoms for intervention. Therefore, screening for psychological distress after discovery of sexual abuse may help detect youth at higher risk for revictimization and guide treatment. PMID- 27386888 TI - Two-Step Freezing in Alkane Monolayers on Colloidal Silica Nanoparticles: From a Stretched-Liquid to an Interface-Frozen State. AB - The crystallization behavior of an archetypical soft/hard hybrid nanocomposite, that is, an n-octadecane C18/SiO2-nanoparticle composite, was investigated by a combination of differential scanning calorimetry (DSC) and variable-temperature solid-state (13)C nuclear magnetic resonance (VT solid-state (13)C NMR) as a function of silica nanoparticles loading. Two latent heat peaks prior to bulk freezing, observed for composites with high silica loading, indicate that a sizable fraction of C18 molecules involve two phase transitions unknown from the bulk C18. Combined with the NMR measurements as well as experiments on alkanes and alkanols at planar amorphous silica surfaces reported in the literature, this phase behavior can be attributed to a transition toward a 2D liquid-like monolayer and subsequently a disorder-to-order transition upon cooling. The second transition results in the formation of a interface-frozen monolayer of alkane molecules with their molecular long axis parallel to the nanoparticles' surface normal. Upon heating, the inverse phase sequence was observed, however, with a sizable thermal hysteresis in accord with the characteristics of the first order phase transition. A thermodynamic model considering a balance of interfacial bonding, chain stretching elasticity, and entropic effects quantitatively accounts for the observed behavior. Complementary synchrotron based wide-angle X-ray diffraction (WAXD) experiments allow us to document the strong influence of this peculiar interfacial freezing behavior on the surrounding alkane melts and in particular the nucleation of a rotator phase absent in the bulk C18. PMID- 27386890 TI - Future Papers. PMID- 27386889 TI - Geophysical Monitoring of Hydrocarbon-Contaminated Soils Remediated with a Bioelectrochemical System. AB - Efficient noninvasive techniques are desired for monitoring the remediation process of contaminated soils. We applied the direct current resistivity technique to image conductivity changes in sandbox experiments where two sandy and clayey soils were initially contaminated with diesel hydrocarbon. The experiments were conducted over a 230 day period. The removal of hydrocarbon was enhanced by a bioelectrochemical system (BES) and the electrical potentials of the BES reactors were also monitored during the course of the experiment. We found that the variation in electrical conductivity shown in the tomograms correlate well with diesel removal from the sandy soil, but this is not the case with the clayey soil. The clayey soil is characterized by a larger specific surface area and therefore a larger surface conductivity. In sandy soil, the removal of the diesel and products from degradation leads to an increase in electrical conductivity during the first 69 days. This is expected since diesel is electrically insulating. For both soils, the activity of BES reactors is moderately imaged by the inverted conductivity tomogram of the reactor. An increase in current production by electrochemically active bacteria activity corresponds to an increase in conductivity of the reactor. PMID- 27386891 TI - Growth Twinning and Generation of High-Frequency Surface Nanostructures in Ultrafast Laser-Induced Transient Melting and Resolidification. AB - The structural changes generated in surface regions of single crystal Ni targets by femtosecond laser irradiation are investigated experimentally and computationally for laser fluences that, in the multipulse irradiation regime, produce sub-100 nm high spatial frequency surface structures. Detailed experimental characterization of the irradiated targets combining electron back scattered diffraction analysis with high-resolution transmission electron microscopy reveals the presence of multiple nanoscale twinned domains in the irradiated surface regions of single crystal targets with (111) surface orientation. Atomistic- and continuum-level simulations performed for experimental irradiation conditions reproduce the generation of twinned domains and establish the conditions leading to the formation of growth twin boundaries in the course of the fast transient melting and epitaxial regrowth of the surface regions of the irradiated targets. The observation of growth twins in the irradiated Ni(111) targets provides strong evidence of the role of surface melting and resolidification in the formation of high spatial frequency surface structures. This also suggests that the formation of twinned domains can be used as a sensitive measure of the levels of liquid undercooling achieved in short pulse laser processing of metals. PMID- 27386892 TI - Immunoproteomic Analysis of Antibody Responses to Extracellular Proteins of Candida albicans Revealing the Importance of Glycosylation for Antigen Recognition. AB - During infection, the human pathogenic fungus Candida albicans undergoes a yeast to-hypha transition, secretes numerous proteins for invasion of host tissues, and modulates the host's immune response. Little is known about the interplay of C. albicans secreted proteins and the host adaptive immune system. Here, we applied a combined 2D gel- and LC-MS/MS-based approach for the characterization of C. albicans extracellular proteins during the yeast-to-hypha transition, which led to a comprehensive C. albicans secretome map. The serological responses to C. albicans extracellular proteins were investigated by a 2D-immunoblotting approach combined with MS for protein identification. On the basis of the screening of sera from candidemia and three groups of noncandidemia patients, a core set of 19 immunodominant antibodies against secreted proteins of C. albicans was identified, seven of which represent potential diagnostic markers for candidemia (Xog1, Lip4, Asc1, Met6, Tsa1, Tpi1, and Prx1). Intriguingly, some secreted, strongly glycosylated protein antigens showed high cross-reactivity with sera from noncandidemia control groups. Enzymatic deglycosylation of proteins secreted from hyphae significantly impaired sera antibody recognition. Furthermore, deglycosylation of the recombinantly produced, secreted aspartyl protease Sap6 confirmed a significant contribution of glycan epitopes to the recognition of Sap6 by antibodies in patient's sera. PMID- 27386893 TI - Nanotherapeutics of PTEN Inhibitor with Mesoporous Silica Nanocarrier Effective for Axonal Outgrowth of Adult Neurons. AB - Development of therapeutic strategies such as effective drug delivery is an urgent and yet unmet need for repair of damaged nervous systems. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) regulates axonal regrowth of central and peripheral nervous systems; its inhibition, meanwhile, facilitates axonal outgrowth of injured neurons. Here we show that nanotherapeutics based on mesoporous silica nanoparticles loading PTEN-inhibitor bisperoxovanadium (BpV) are effective for delivery of drug molecules and consequent improvement of axonal outgrowth. Mesoporous nanocarriers loaded BpV drug at large amount (27 MUg per 1 mg of carrier), and released sustainably over 10 d. Nanocarrier-BpV treatment of primary neurons from the dorsal root ganglions (DRGs) of rats and mice at various concentrations induced them to actively take up the nanocomplexes with an uptake efficiency as high as 85%. The nanocomplex-administered neurons exhibited significantly enhanced axonal outgrowth compared with those treated with free-BpV drug. The expression of a series of proteins involved in PTEN inhibition and downstream signaling was substantially up-/down-regulated by the nanocarrier-BpV system. Injection of the nanocarriers into neural tissues (DRG, brain cortex, and spinal cord), moreover, demonstrated successful integration into neurons, glial cells, oligodendrocytes, and macrophages, suggesting the possible nanotherapeutics applications in vivo. Together, PTEN-inhibitor delivery via mesoporous nanocarriers can be considered a promising strategy for stimulating axonal regeneration in central and peripheral nervous systems. PMID- 27386894 TI - Detection of Zika virus RNA in whole blood of imported Zika virus disease cases up to 2 months after symptom onset, Israel, December 2015 to April 2016. AB - Zika virus RNA presence in serum, whole-blood and urine samples from six Israeli travellers symptomatic for Zika virus disease was examined. Whole-blood samples were positive for as late as 2 months (58 days) post-symptom onset, longer than for urine (26 days) and serum (3 days). These findings suggest the utility of whole blood in Zika infection diagnosis. PMID- 27386895 TI - Measles seroprevalence, outbreaks, and vaccine coverage in Rwanda. AB - BACKGROUND: Measles outbreaks are reported after insufficient vaccine coverage, especially in countries recovering from natural disaster or conflict. We compared seroprevalence to measles in blood donors in Rwanda and Sweden and explored distribution of active cases of measles and vaccine coverage in Rwanda. METHODS: 516 Rwandan and 215 Swedish blood donors were assayed for measles-specific immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA). Data on vaccine coverage and acute cases in Rwanda from 1980 to 2014 were collected, and IgM on serum samples and polymerase chain reaction (PCR) on nasopharyngeal (NPH) swabs from suspected measles cases during 2010-2011 were analysed. RESULTS: The seroprevalence of measles IgG was significantly higher in Swedish blood donors (92.6%; 95% CI: 89.1-96.1%) compared to Rwandan subjects (71.5%; 95% CI: 67.6 75.4%) and more pronounced <35 years of age. The OD values were significantly lower in the Rwandan blood donors as compared to Swedish subjects (p < 0.00001). However, effective measles vaccine coverage was concomitant with decrease in measles cases in Rwanda, with the exception of an outbreak in 1995 following the 1994 genocide. 76/544 serum samples were IgM positive and 21/31 NPH swabs were PCR positive for measles, determined by sequencing to be of genotype B3. CONCLUSIONS: Measles seroprevalence was lower in Rwandan blood donors compared to Swedish subjects. Despite this, the number of reported measles cases in Rwanda rapidly decreased during the study period, concomitant with increased vaccine coverage. Taken together, the circulation of measles was limited in Rwanda and vaccine coverage was favourable, but seroprevalence and IgG levels were low especially in younger age groups. PMID- 27386897 TI - The Center of Chaos. PMID- 27386896 TI - Computerized dynamic posturography detects balance deficits in individuals with a history of chronic severe traumatic brain injury. AB - BACKGROUND: Mild balance deficits can be challenging to detect in individuals with long-standing traumatic brain injuries. This study compared Computerized Dynamic Posturography (CDP) scores from individuals with traumatic brain injuries (TBI) to controls to determine if CDP could differentiate between the two groups and determine if there was a learning effect associated with testing that could be used to guide evaluation of baseline balance. METHODS: Ten ambulatory individuals with a history of severe TBI and 10 individuals without participated in three CDP sessions (24-72 hours apart). During each session, participants performed the Berg Balance Test, Dynamic Gait Index and three trials of a standardized balance assessment and Dynamic Movement Analysis (DMA) scores were recorded for each test. RESULTS: Individuals with TBI scored 93% higher (i.e. reflecting poorer balance) than the control group. The group with TBI exhibited 6.6-times more variability compared to the control group, with estimated variances of 0.3407 and 0.0517, respectively. A learning effect was detected in the group with TBI on the first day of testing (betaTBI F = -0.1241, p-value < 0.01). DISCUSSION: The CDP system detected balance differences between individuals with TBI and controls. Given the documented learning effect, the best of three trials should be used to accurately assess baseline scores. PMID- 27386899 TI - First-line treatment in NSCLC harboring EGFR common mutations: EGFR TKI in monotherapy or in combination with anti-VEGF? PMID- 27386898 TI - The Theory of Planned Behavior as it predicts potential intention to seek mental health services for depression among college students. AB - BACKGROUND: Between 9.5% and 31.3% of college students suffer from depression (American college health association national college health assessment II: reference group executive summary spring 2013. Amer. Coll. Health Assoc. 2013; Eagan K, Stolzenberg EB, Ramirez JJ, Aragon, MC, Suchard, RS, Hurtado S. The American freshman: national norms fall 2014. Higher Educ. Res. Inst.; 2015). Universities need to understand the factors that relate to care-seeking behavior. OBJECTIVE: Across 3 studies, to relate attitudes, social norms, and perceived behavioral control to intention to seek mental health services, and to investigate barriers to care-seeking. PARTICIPANTS: University college students (N = 845, 64% female, 26% male, and 10% unspecified). METHODS: New measures were created in Studies 1 and 2, and were examined using structural equation modeling in Study 3. RESULTS: Partially consistent with the Theory of Planned Behavior (Ajzen, I, Fishbein, M. Understanding Attitudes and Predicting Social Behavior. Englewood Cliffs, NJ: Prentice-Hall; 1980), a model with an excellent fit revealed that more positive attitudes about care and higher perceived behavioral control directly predicted higher intention to seek mental health services. CONCLUSIONS: Educating college students about mental health disorders and treatments, enhancing knowledge about available services, and addressing limited access to long-term care might improve treatment rates for students suffering from depression. PMID- 27386900 TI - HIV P24 antigen among HIV antibody seronegative blood donors in Osogbo Osun State, South Western Nigeria. AB - BACKGROUND: Efforts to curb the spread of HIV transmission through transfusion of blood and its products is still a problem because of challenge in countries using antibody-based rapid methods to detect infection during window period. Transmission of HIV through infected blood and its products accounts for approximately 10% in African region. METHODS: This study analyzed true negativity of HIV infection in blood donors screened by ELISA test based on p24 core antigen detection. Four hundred and eighty (480) blood donors initially negative for HIV antibody by rapid screening kit, DetermineTM HIV-1/2 (Abbott Laboratory, IL, USA) and re-screened with Immuno Comb(r) II HIV 1 and 2 (Bispot kit PBS Organics and Israel 2005). The samples were further tested for the presence of HIV antibody and p24 HIV core antigen using ELISA kits (Genscreen TM ULTRA HIV Ag-Ab) following manufacturer's instructions. All donors initially tested negative for Hepatitis B virus, Hepatitis C virus. RESULT: Two (0.42%) of 480 blood donors tested positive for the p24 HIV core antigen. The two positive donors for the p24 antigen had multiple sexual partners and recent sexually transmitted infections. CONCLUSION: The association of the HIV p24 antigen with blood donation was highly significant (p = 0.000) and pose a great risk to recipients if screening of blood donor is only carried out by HIV antibody detection. PMID- 27386909 TI - Risks of UpToDate medicine. PMID- 27386901 TI - Cationic liposomes produced via ethanol injection method for dendritic cell therapy. AB - Cationic liposomes can be designed and developed in order to be an efficient gene delivery system for mammalian cells. Dendritic cell (DC) vaccines can be used to treat cancer, as cationic liposomes can deliver tumor antigens to cells while cells remain active. However, most methods used for liposome production are not able to reproduce in large scale the physicochemical and biological properties of liposomes produced in laboratory scale. In this context, ethanol injection method achieved promising results, although requiring post-treatment for size reduction and/or to remove residual ethanol. Thus, the purpose of this study was to generate cationic liposomes suitable for gene therapies via ethanol injection method in only one step (VEI) and compared to those submitted to a size reduction processes by microfluidization (MFV). For this, the method to produce cationic liposomes composed of egg phosphatidylcholine (EPC), 1,2-dioleoyl-3 trimethylammonium propane (DOTAP) and 1,2-dioleoylphosphatidylethanolamine (DOPE) was optimized using a statistical design approach. As a result, the size of VEI decreased from 290 nm to 110 nm and the polydispersity from 0.54 to 0.17. In the case of MFV, size decreased from 128 nm to 107 nm and polydispersity from 0.40 to 0.18. ST and MFV before and after optimization were also characterized in terms of morphology by transmission electron microscopy (TEM) and structure by differential scanning calorimetry (DSC). Finally, to show their potential in gene/immune therapies applications, DCs were stimulated by such liposomes. Cells internalized liposomes, increasing expression of the costimulatory molecule CD86 and inducing T lymphocyte proliferation. PMID- 27386910 TI - [Les risques de la medecine fondee sur les donnees les plus recentes]. PMID- 27386912 TI - [Message du president. L'urbanisation des soins medicaux]. PMID- 27386911 TI - President's message. The urbanization of medical care. PMID- 27386913 TI - Use of Admail and a geographic information system to send surveys to target populations. AB - INTRODUCTION: This paper briefly describes the use of Canada Post Unaddressed Admail and a geographic information system (GIS) for survey distribution to a specific target population in a large, sparsely populated geographic area, and the effectiveness of this approach. METHODS: Surveys were sent as Unaddressed Admail via Canada Post to a target population of people living within 5 km of a wind turbine in southwestern Ontario. RESULTS: The overall response rate from 8 wind farms (in 8 counties) was 8.1%. CONCLUSION: This approach has the potential to save time and money, but low response rates are common, distribution is not precise and there is potential for selection bias. Despite these flaws, Unaddressed Admail is worth consideration for delivery of information, study recruitment materials and surveys to rural, remote and specific target populations. PMID- 27386914 TI - Rural residence and risk of dementia. AB - INTRODUCTION: We sought to determine whether residence in a rural region is associated with a higher risk of dementia and a higher risk of developing dementia over a 5-year period than residence in an urban region. METHODS: This was a secondary analysis of a prospective cohort study. In 1991 and 1992, 1751 adults aged 65 years and older and residing in the community were sampled from a representative population-based registry, which included the entire province (time 1). Follow-up occurred 5 years later (time 2). Age, sex and education were selfreported. Rurality was determined by the population of the Census subdivision, with a population greater than 19 999 considered urban. Cognition was assessed using the Modified Mini-Mental State Examination, with those scoring below 78 invited to undergo a clinical examination to determine the presence of dementia. Cross-sectional analyses were conducted for participants with complete data at time 1. Prospective analyses were conducted for participants with normal cognition at time 1, who had complete data and survived until time 2. Logistic regression models were constructed for the outcome of dementia at times 1 and 2. RESULTS: Residence in a rural region was not associated with dementia in the cross-sectional analyses (adjusted odds ratio [OR] 1.08, 95% confidence interval [CI] 0.61-1.91) and did not predict dementia 5 years later (adjusted OR 1.05, 95% CI 0.66-1.68). CONCLUSION: We found no difference in the risk of dementia among older adults living in urban and rural regions of Manitoba. PMID- 27386915 TI - The occasional regional nerve block of the hand. PMID- 27386916 TI - Digital nerve block. PMID- 27386917 TI - Digital nerve block - The author responds. PMID- 27386918 TI - Extending the line: the First Nations Telehealth Expansion Project. PMID- 27386919 TI - A new fun and robust version of an fMRI localizer for the frontotemporal language system. AB - A set of brain regions in the frontal, temporal, and parietal lobes supports high level linguistic processing. These regions can be reliably identified in individual subjects using fMRI, by contrasting neural responses to meaningful and structured language stimuli vs. stimuli matched for low-level properties but lacking meaning and/or structure. We here present a novel version of a language 'localizer,' which should be suitable for diverse populations including children and/or clinical populations who may have difficulty with reading or cognitively demanding tasks. In particular, we contrast responses to auditorily presented excerpts from engaging interviews or stories, and acoustically degraded versions of these materials. This language localizer is appealing because it uses (a) naturalistic and engaging linguistic materials, (b) auditory presentation, PMID- 27386921 TI - Direct imaging discovery of a Jovian exoplanet within a triple-star system. AB - Direct imaging allows for the detection and characterization of exoplanets via their thermal emission. We report the discovery via imaging of a young Jovian planet in a triple-star system and characterize its atmospheric properties through near-infrared spectroscopy. The semimajor axis of the planet is closer relative to that of its hierarchical triple-star system than for any known exoplanet within a stellar binary or triple, making HD 131399 dynamically unlike any other known system. The location of HD 131399Ab on a wide orbit in a triple system demonstrates that massive planets may be found on long and possibly unstable orbits in multistar systems. HD 131399Ab is one of the lowest mass (4 +/ 1 Jupiter masses) and coldest (850 +/- 50 kelvin) exoplanets to have been directly imaged. PMID- 27386920 TI - Early-life nutrition modulates the epigenetic state of specific rDNA genetic variants in mice. AB - A suboptimal early-life environment, due to poor nutrition or stress during pregnancy, can influence lifelong phenotypes in the progeny. Epigenetic factors are thought to be key mediators of these effects. We show that protein restriction in mice from conception until weaning induces a linear correlation between growth restriction and DNA methylation at ribosomal DNA (rDNA). This epigenetic response remains into adulthood and is restricted to rDNA copies associated with a specific genetic variant within the promoter. Related effects are also found in models of maternal high-fat or obesogenic diets. Our work identifies environmentally induced epigenetic dynamics that are dependent on underlying genetic variation and establishes rDNA as a genomic target of nutritional insults. PMID- 27386922 TI - Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor. AB - The ongoing Zika virus (ZIKV) outbreak is linked to severe neurological disorders. ZIKV relies on its NS2B/NS3 protease for polyprotein processing; hence, this enzyme is an attractive drug target. The 2.7 angstrom; crystal structure of ZIKV protease in complex with a peptidomimetic boronic acid inhibitor reveals a cyclic diester between the boronic acid and glycerol. The P2 4-aminomethylphenylalanine moiety of the inhibitor forms a salt-bridge with the nonconserved Asp(83) of NS2B; ion-pairing between Asp(83) and the P2 residue of the substrate likely accounts for the enzyme's high catalytic efficiency. The unusual dimer of the ZIKV protease:inhibitor complex seen in the crystal may provide a model for assemblies formed at high local concentrations of protease at the endoplasmatic reticulum membrane, the site of polyprotein processing. PMID- 27386923 TI - Light-dependent chlorophyll f synthase is a highly divergent paralog of PsbA of photosystem II. AB - Chlorophyll f (Chl f) permits some cyanobacteria to expand the spectral range for photosynthesis by absorbing far-red light. We used reverse genetics and heterologous expression to identify the enzyme for Chl f synthesis. Null mutants of "super-rogue" psbA4 genes, divergent paralogs of psbA genes encoding the D1 core subunit of photosystem II, abolished Chl f synthesis in two cyanobacteria that grow in far-red light. Heterologous expression of the psbA4 gene, which we rename chlF, enables Chl f biosynthesis in Synechococcus sp. PCC 7002. Because the reaction requires light, Chl f synthase is probably a photo-oxidoreductase that employs catalytically useful Chl a molecules, tyrosine YZ, and plastoquinone (as does photosystem II) but lacks a Mn4Ca1O5 cluster. Introduction of Chl f biosynthesis into crop plants could expand their ability to use solar energy. PMID- 27386925 TI - Fatal ischemic stroke following Tityus serrulatus scorpion sting in a patient with essential thrombocythemia. AB - CONTEXT: Stroke following scorpion stings is rare. We report a fatal envenomation involving multiple, extensive brain infarcts in a patient with a previous diagnosis of essential thrombocythemia (ET) who was stung by Tityus serrulatus (T. serrulatus). CASE DETAILS: A 44-year-old woman with a diagnosis of low-risk ET (platelets <1,000,000/mm3, age <60 years and no history of thrombosis; positive JAK2V617F mutation) was admitted to a local ED 1 h after being stung by T. serrulatus on the left foot. She developed signs of severe envenomation, including several episodes of profuse vomiting, pallor and confusion soon after the sting, followed by shock (BP: 90/60 to 60/40 mmHg) and was treated with scorpion antivenom, vasopressors and mechanical ventilation. A brain computed tomography (CT) scan (54-h poststing) revealed diffuse bilateral cerebellar hypodensity, with partial involvement of both occipital lobes and thalamus, obstructive hydrocephaly with signs of cerebrospinal fluid extravasation, and ascending transtentorial herniation, suggestive of bilateral ischemia involving the posterior cerebral circulation. External ventricular drainage resulted in no improvement and brain death was confirmed on day 10. DISCUSSION: Several mechanisms have been proposed to explain stroke following scorpion stings, such as sympathetic stimulation, myocardial dysfunction, hypotension/shock, arrhythmias and coagulopathy. Ischemic stroke is one of the most serious complications of ET. The risk factors for thrombotic/ischemic events in patients with ET include age (>=60 years) and previous vascular events. Severe scorpion envenomation resulting in myocardial dysfunction and systemic inflammatory response syndrome may increase the overall risk of arterial thrombosis in this patient. PMID- 27386924 TI - Novel Monoclonal Antibodies for Studies of Human and Rhesus Macaque Secretory Component and Human J-Chain. AB - Immunoglobulin A (IgA) antibodies exist in monomeric, dimeric, and secretory forms. Dimerization of IgA depends on a 15-kD polypeptide termed "joining (J) chain," which is also part of the binding site for an epithelial glycoprotein called "secretory component (SC)," whether this after apical cleavage on secretory epithelia is ligand bound in secretory IgA (SIgA) or in a free form. Uncleaved membrane SC, also called the "polymeric Ig receptor," is thus crucial for transcytotic export of SIgA to mucosal surfaces, where it interacts with and modulates commensal bacteria and mediates protective immune responses against exogenous pathogens. To evaluate different forms of IgA, we have produced mouse monoclonal antibodies (MAbs) against human J-chain and free SC. We found that J chain MAb 9A8 and SC MAb 9H7 identified human dimeric IgA and SIgA in enzyme linked immunoassay and western blot analysis, as well as functioning in immunohistochemistry to identify cytoplasmic IgA of intestinal lamina propria plasmablasts/plasma cells and crypt epithelium of distal human intestine. Finally, we demonstrated that SC MAb 9H7 cross-reacted with rhesus macaque SIgA. These novel reagents should be of use in the study of the biology of various forms of IgA in humans and SIgA in macaques, as well as in monitoring the production and/or isolation of these forms of IgA. PMID- 27386926 TI - Risk factors for recurrence of pleomorphic adenoma. AB - Pleomorphic adenoma is the most frequent benign tumor of the salivary glands. It is characterized by a tendency to recur, which is determined by the biological characteristics of the tumor as well as the mode of its treatment. Recurrence of the tumor is associated with a high risk of postoperative facial palsy, risk of subsequent recurrence after revision surgery, and an increased risk of malignant transformation. Knowledge of the recurrence risk factors could allow selection of treatments that minimize the risk. Among the factors in this study the most important are: incomplete excision, intraoperative capsule rupture, myxoid subtype, presence of the satellite nodules and tumor extensions (pseudopodia), lack of the glandular tissue margin and the experience of the surgeon. The possible factors are: the female sex, young age, location and size of the tumor, and the duration of the tumor growth. The technique of tumor enucleation of pleomorphic adenoma carries a high risk of recurrence and should be replaced by parotidectomy. In cases of recurrence the treatment is individually tailored and may: further follow up, limited resection of the tumor, lateral parotidectomy or extended radical parotidectomy with concurrent reconstruction of the facial nerve. The role of radiotherapy is discussed. PMID- 27386927 TI - Do we need a new classification of parotid gland surgery? AB - BACKGROUND: In February 2016 the European Salivary Gland Society (ESGS) presented and recommended classification of parotidectomies based on the anatomical I-V level division of parotid gland. The main goal of this paper is to present the new classification, and to answer the question if it is more precise compared to classic one. MATERIAL AND METHOD: 607 patients (315 man, 292 women) operated on for parotid tumours in a tertiary referral centre, Department of Otolaryngology, Head and Neck Surgery, Medical University of Poznan (502 benign and 105 malignant tumours). Parotid surgery descriptions provided by retrospective analysis of all operating protocols covering the years 2006-2015 were "translated" into the new classification proposed by the ESGS. RESULTS: Analysis of operating protocols and fitting them into the new classification proposed by the ESGS show some discrepancies, in both benign and malignant tumours. Based on the re-evaluation of 607 cases, in 94 procedures for benign tumors the only information available was that "surgery was performed within the superficial lobe". Thus, the new classification forces the surgeon to be much more precise than previously. In 3 cases the whole superficial lobe was removed, together with the upper part of the deep lobe. Because the classification lacked parotidectomy I-II-IV, it indicated that the new classification was insufficient in the aforementioned three cases. In 6 cases of ECD more than one parotid gland tumour was removed. Among malignant tumours, total parotidectomy was the predominant procedure. In 3/13 cases of expanded parotidectomy the temporomandibular joint (TMJ) was additionally removed and it seems that the acronym TMJ should be included among the additional resected structures. It is also necessary to supplement the description of the treatment with casuistically resected anatomical structures for oncological purposes (RT planning) and follow-up imaging. Currently, since 2015 in Poland there has been the National Cancer Registry of benign salivary gland tumours (https://guzyslinianek.pcss.pl). New surgical anatomy and classification based on it will be very helpful in unequivocal, albeit brief and not laborious, reporting of procedures. To summarize, the classification is: easy to use, precise, and forced the surgeon to make a detailed description saving time at the same time. Although it is broad and accurate, it did not cover all clinically rare cases, multiple foci and it does not contain key information about the rupture of the tumour's capsule, so it is necessary to complement the type of surgery by this annotations. The simple, clear and comprehensive classification is especially valuable for centres that lead registration. Thus, we are personally grateful for this new classification, which facilitates multicentre communication. PMID- 27386928 TI - The rising incidence of papillary thyroid microcarcinoma and is completion surgery necessary or not? AB - Papillary thyroid microcarcinoma (PTMC) is defined as a papillary cancer that is 1 cm or less in its maximal diameter. The incidence of thyroid cancer has increased during the past 30 years. The aim of this study is to evaluate the rising incidence of PTMC (papillary thyroid microcarcinoma) and whether is lobectomy enough or not. The data of 462 consecutive patients who underwent thyroidectomy (hemithyroidectomy and total thyroidectomy) at the Hacettepe University Hospitals Department of ENT from 2000 to 2015 were analyzed. Surgical procedure, histopathologic examinations, postoperative complications, follow-up time and mortality were recorded. USG and FNAC were performed on all cases. Of the 344 patients with thyroid malignancy and 118 patients underwent total laryngectomy with thyroidectomy. 364 patients with TT and 98 patients with HT. The first group included 204 patients (Surgery time 2000-2007), 91 of them ( 44.6%) had PTMC. The second group included 258 patients, 192of them (74,4%) had PTMC (p<0.001). 22 Patients with PTMC underwent completion surgery and 40 of them just followed by hemithyroidectomy. There was no recurrence. PTMC has been rising incidence because of ,pathological and radiological, increased awareness and completion surgery is not necessary for all PTMC cases especially incidental PTMC. PMID- 27386929 TI - GJB2 sequencing in deaf and profound sensorineural hearing loss children. AB - INTRODUCTION: GJB2 mutations are the most frequent reason of genetic congenital hearing loss. The aim of the study was to assess the prevalence of GJB2 mutations in the deaf and profound hearing loss children. MATERIAL AND METHODS: The material of the study was a group of 61 patients divided into two groups. Group I - 35 deaf or with profound sensorineural hearing loss children (the pupils of the deaf and hard of hearing school), aged 5-17 years (average 9.2 years), 14 males, 21 females, II - control group comprised 26 normal hearing patients, aged 5-16 years (average 10.4years), 14 males, 12 females (patients of Department of Pediatric Otolaryngology, Audiology and Phoniatrics, Medical University of Lodz). In both groups, exon 2 sequencing of GJB2 gene was performed. RESULTS: In group I in 6 patients (17%) 35delG in GJB2 gene was found. The patients were homozygotes, with negative family history of hearing loss. No other mutations in GJB2 gene were found. In group II no mutations in GJB2 were observed. CONCLUSIONS: The most frequent cause of hearing impairment in the deaf and profound sensorineural hearing loss children was 35delG mutation in GJB2 gene. No other mutations in GJB2 gene were detected. PMID- 27386930 TI - Analysis of hearing improvement in the patients operated on due to otosclerosis in the Otolaryngology Department of Jagiellonian University of Cracow, Poland. AB - BACKGROUND: Otosclerosis is the most common cause of condactive hearing loss between 15 and 50 years old. The most common symptoms are hearinglosss and tinnitus. Surgery is currently the preferred treatment method. AIM: The aim of our study was to analyze the outcomes of patients treated surgically due to otosclerosis in terms of the observed changes in pure tone audiometry and speech audiometry Material and methods: We observated 300 patients operated on middle ear for the fist time in the Department of Otolarygology at the Jagiellonian University of Cracow from 2010 to 2011. We used a special questinnaire which includes diagnostics of the ear"s disease,pure tone audiometry, speech audiometrii and longterm effects. RESULTS: We discuss 53 operated ears and analyze changes in pure tone audiometry. We divided patients into 2 groups depending on 100% speech understanding in speech auodiometry or not. CONCLUSION: 1. Lack of 100% speech understanding in speech audiometry correlated with greater sensorineural hearing loss than in patients who achieved 100% speech understanding prior to surgery. 2. Lack of 100% speech understanding in speech audiometry is a predictive factor for worse prognosis in improving hearing in patients operated on for otosclerosis. 3. Reconstruction of the ossicular chain in patients, regardless of the degree of speech understanding, did not produce significant changes in the average values of bone conduction. PMID- 27386931 TI - Matrix metalloproteinases MMP1, MMP2, MMP9 and their tissue inhibitors TIMP1, TIMP2, TIMP3 in head and neck cancer: an immunohistochemical study. AB - INTRODUCTION: Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes implicated in the invasion and metastasis of many kinds of cancer because of their ability to degrade components of extracellular matrix. Specific tissue inhibitors of matrix metalloproteinases (TIMPs) regulate their activity. MMPs and TIMPs were identified in many neoplasm, including cancers of head and neck, lung, breast and colon cancer. In most researches a strong relation between MMPs and TIMPs expression and a clinical course of disease was observed, although there were many discrepancies between the authors. The aim of this research was to evaluate the expression of MMP1, MMP2, MMP9 and TIMP1, TIMP2, TIMP3 in head and neck cancer and to investigate the prognostic impact of these factors in patients with these tumors. MATERIAL AND METHODS: 210 patients with head and neck cancer that underwent surgical treatment with at least a 5-year follow-up were included in the study. Immunohistochemical studies were performed on formalin fixed, paraffin embedded sections by using monoclonal antibodies against MMP1, MMP2, MMP9 and TIMP1, TIMP2, TIMP3 antigens and Dako EnVision detection system. RESULTS: For all of the markers diffusion, cytoplasmatic staining of tumor cells and some surrounding stromal cells was observed. There was a correlation between TIMP2 and TIMP3 overexpression and tumors staged as III/IV (p=0,037 and p=0,022, respectively). Also, we observed a strong association between MMP2 expression and the presence of nodal metastases (p=0,013). It was found that the TIMP2 overexpression was significantly more frequent in the tumors of patients facing nodal recurrences during the follow-up period (p=0,05). Positive immunostainings of MMP1, MMP2, MMP9 and TIMP1, TIMP2 were significantly related to the higher tumor grade (G3). Specially strong correlation was seen between high TIMP2 expression and low histological differentiation (G3) (p<0,001). In univariate analysis the overall survival rate was shorter in cases with positive MMP2 and/or MMP9 expression. Patients with TIMP2 positive expression diminished both overall and disease-free survival (p=0,049). In multivariate analysis positive TIMP2 and MMP2 expressions were independent prognostic factors for overall survival. Only advanced nodal metastatic tumors (N3) were related to disease free survival. CONCLUSIONS: Our data suggest the conclusion that imbalance between matrix metalloproteinases and their inhibitors play the important role in progression of head and neck cancer and patients' prognosis. PMID- 27386932 TI - Recombination Processes and Nonlinear Markov Chains. AB - Bacteria are known to exchange genetic information by horizontal gene transfer. Since the frequency of homologous recombination depends on the similarity between the recombining segments, several studies examined whether this could lead to the emergence of subspecies. Most of them simulated fixed-size Wright-Fisher populations, in which the genetic drift should be taken into account. Here, we use nonlinear Markov processes to describe a bacterial population evolving under mutation and recombination. We consider a population structure as a probability measure on the space of genomes. This approach implies the infinite population size limit, and thus, the genetic drift is not assumed. We prove that under these conditions, the emergence of subspecies is impossible. PMID- 27386933 TI - Early Identification and Prevention of the Spread of Ebola - United States. AB - In response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa, CDC prepared for the potential introduction of Ebola into the United States. The immediate goals were to rapidly identify and isolate any cases of Ebola, prevent transmission, and promote timely treatment of affected patients. CDC's technical expertise and the collaboration of multiple partners in state, local, and municipal public health departments; health care facilities; emergency medical services; and U.S. government agencies were essential to the domestic preparedness and response to the Ebola epidemic and relied on longstanding partnerships. CDC established a comprehensive response that included two new strategies: 1) active monitoring of travelers arriving from countries affected by Ebola and other persons at risk for Ebola and 2) a tiered system of hospital facility preparedness that enabled prioritization of training. CDC rapidly deployed a diagnostic assay for Ebola virus (EBOV) to public health laboratories. Guidance was developed to assist in evaluation of patients possibly infected with EBOV, for appropriate infection control, to support emergency responders, and for handling of infectious waste. CDC rapid response teams were formed to provide assistance within 24 hours to a health care facility managing a patient with Ebola. As a result of the collaborations to rapidly identify, isolate, and manage Ebola patients and the extensive preparations to prevent spread of EBOV, the United States is now better prepared to address the next global infectious disease threat.The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html). PMID- 27386934 TI - Symptoms and delay times during myocardial infarction in 694 patients with and without diabetes; an explorative cross-sectional study. AB - BACKGROUND: In myocardial infarction (MI) a short pre-hospital delay, prompt diagnosis and timely reperfusion treatment can improve the prognosis. Despite the importance of timely care seeking, many patients with MI symptoms delay seeking medical care. Previous research is inconclusive about differences in symptom presentation and pre-hospital delay between patients with and without diabetes during MI. The aim of this study was to describe symptoms and patient delay during MI in patients with and without diabetes. METHODS: Swedish cross-sectional multicentre survey study enrolling MI patients in 5 centres within 24 h from admittance. RESULTS: Chest pain was common in patients both with and without diabetes and did not differ after adjustment for age and sex. Patients with diabetes had higher risk for shoulder pain/discomfort, shortness of breath, and tiredness, but lower risk for cold sweat. The three most common symptoms reported by patients with diabetes were chest pain, pain in arms/hands and tiredness. In patients without diabetes the most common symptoms were chest pain, cold sweat and pain in arms/hands. Median patient delay time was 2 h, 24 min for patients with diabetes and 1 h, 15 min for patients without diabetes (p = 0.024). CONCLUSION: Chest pain was common both in patients with and without diabetes. There were more similarities than differences in MI symptoms between patients with and without diabetes but patients with diabetes had considerably longer delay. This knowledge is important not only for health care personnel meeting patients with suspected MI, but also for the education of people with diabetes. PMID- 27386935 TI - Do the Apoe-/- and Ldlr-/- Mice Yield the Same Insight on Atherogenesis? AB - Murine models of atherosclerosis are useful for investigating the environmental and genetic influences on lesion formation and composition. Apoe(-/-) and Ldlr(-/ ) mice are the 2 most extensively used models. The models differ in important ways with respect to the precise mechanism by which their absence enhances atherosclerosis, including differences in plasma lipoproteins. The majority of the gene function studies have utilized only 1 model, with the results being generalized to atherogenic mechanisms. In only a relatively few cases have studies been conducted in both atherogenic murine models. This review will discuss important differences between the 2 atherogenic models and will point out studies that have been performed in the 2 models where results are comparable and those where different results were obtained. PMID- 27386936 TI - Osteoclastogenic Differentiation of Macrophages in the Development of Abdominal Aortic Aneurysms. AB - OBJECTIVE: Arterial calcification is common and contributes to the pathogenesis of occlusive vascular disease. Similar to the dynamics of bone, it is a tightly controlled process that maintains a balance between osteogenesis and osteolysis. However, whether calcium homeostasis plays a role in the development of aneurysms has not been explored. We hypothesized that macrophages differentiate into osteoclasts in aneurysmal arteries and that protease byproducts contribute to aneurysm pathophysiology. APPROACH AND RESULTS: We performed histological and immunohistochemical analyses and showed that macrophages positive for several osteoclast markers, including tartrate acid phosphatase, occur in great numbers in the human aneurysmal aorta, but very few occur in the human stenotic aorta and none in the nondiseased human aorta. Moreover, in situ zymography showed elevated protease activity in these cells compared with undifferentiated macrophages. Tumor necrosis factor-alpha and calcium phosphate stimulated this osteoclastogenic differentiation process through nuclear factor-kappaB, mitogen activated protein kinases, and intracellular calcium signaling but not the receptor activator of the nuclear factor-kappaB ligand. Inhibition of osteoclastogenic differentiation by bisphosphonate inhibits aneurysm development in a mouse model. CONCLUSIONS: These results suggest that differentiation of macrophages into osteoclasts contributes to the pathophysiology of aneurysmal disease. PMID- 27386937 TI - 2014 Jeffrey M. Hoeg Award Lecture: Transcriptional Control of Monocyte Development. AB - Monocytes and macrophages are key immune cells involved in the early progression of atherosclerosis. Transcription factors that control their development in the bone marrow are important therapeutic targets to control the numbers and functions of these cells in disease. This review highlights what is currently known about the transcription factors that are critical for monocyte development. PMID- 27386938 TI - S100A6 Regulates Endothelial Cell Cycle Progression by Attenuating Antiproliferative Signal Transducers and Activators of Transcription 1 Signaling. AB - OBJECTIVE: S100A6, a member of the S100 protein family, has been described as relevant for cell cycle entry and progression in endothelial cells. The molecular mechanism conferring S100A6's proliferative actions, however, remained elusive. APPROACH AND RESULTS: Originating from the clinically relevant observation of enhanced S100A6 protein expression in proliferating endothelial cells in remodeling coronary and carotid arteries, our study unveiled S100A6 as a suppressor of antiproliferative signal transducers and activators of transcription 1 signaling. Discovery of the molecular liaison was enabled by combining gene expression time series analysis with bioinformatic pathway modeling in S100A6-silenced human endothelial cells stimulated with vascular endothelial growth factor A. This unbiased approach led to successful identification and experimental validation of interferon-inducible transmembrane protein 1 and protein inhibitors of activated signal transducers and activators of transcription as key components of the link between S100A6 and signal transducers and activators of transcription 1. CONCLUSIONS: Given the important role of coordinated endothelial cell cycle activity for integrity and reconstitution of the inner lining of arterial blood vessels in health and disease, signal transducers and activators of transcription 1 suppression by S100A6 may represent a promising therapeutic target to facilitate reendothelialization in damaged vessels. PMID- 27386939 TI - New Functional Tools for Antithrombogenic Activity Assessment of Live Surface Glycocalyx. AB - OBJECTIVE: It is widely accepted that the presence of a glycosaminoglycan-rich glycocalyx is essential for endothelialized vasculature health; in fact, a damaged or impaired glycocalyx has been demonstrated in many vascular diseases. Currently, there are no methods that characterize glycocalyx functionality, thus limiting investigators' ability to assess the role of the glycocalyx in vascular health. APPROACH AND RESULTS: We have developed novel, easy-to-use, in vitro assays that directly quantify live endothelialized surface's functional heparin weights and their anticoagulant capacity to inactivate Factor Xa and thrombin. Using our assays, we characterized 2 commonly used vascular models: native rat aorta and cultured human umbilical vein endothelial cell monolayer. We determined heparin contents to be ~10 000 ng/cm(2) on the native aorta and ~10-fold lower on cultured human umbilical vein endothelial cells. Interestingly, human umbilical vein endothelial cells demonstrated a 5-fold lower anticoagulation capacity in inactivating both Factor Xa and thrombin relative to native aortas. We verified the validity and accuracy of the novel assays developed in this work using liquid chromatography-mass spectrometry analysis. CONCLUSIONS: Our assays are of high relevance in the vascular community because they can be used to establish the antithrombogenic capacity of many different types of surfaces such as vascular grafts and transplants. This work will also advance the capacity for glycocalyx targeting therapeutics development to treat damaged vasculatures. PMID- 27386940 TI - Endothelial Dysfunction, and A Prothrombotic, Proinflammatory Phenotype Is Caused by Loss of Mitochondrial Thioredoxin Reductase in Endothelium. AB - OBJECTIVE: Although the investigation on the importance of mitochondria-derived reactive oxygen species (ROS) in endothelial function has been gaining momentum, little is known on the precise role of the individual components involved in the maintenance of a delicate ROS balance. Here we studied the impact of an ongoing dysregulated redox homeostasis by examining the effects of endothelial cell specific deletion of murine thioredoxin reductase 2 (Txnrd2), a key enzyme of mitochondrial redox control. APPROACH AND RESULTS: We analyzed the impact of an inducible, endothelial cell-specific deletion of Txnrd2 on vascular remodeling in the adult mouse after femoral artery ligation. Laser Doppler analysis and histology revealed impaired angiogenesis and arteriogenesis. In addition, endothelial loss of Txnrd2 resulted in a prothrombotic, proinflammatory vascular phenotype, manifested as intravascular cellular deposits, as well as microthrombi. This phenotype was confirmed by an increased leukocyte response toward interleukin-1 in the mouse cremaster model. In vitro, we could confirm the attenuated angiogenesis measured in vivo, which was accompanied by increased ROS and an impaired mitochondrial membrane potential. Ex vivo analysis of femoral arteries revealed reduced flow-dependent vasodilation in endothelial cell Txnrd2 deficient mice. This endothelial dysfunction could be, at least partly, ascribed to inadequate nitric oxide signaling. CONCLUSIONS: We conclude that the maintenance of mitochondrial ROS via Txnrd2 in endothelial cells is necessary for an intact vascular homeostasis and remodeling and that Txnrd2 plays a vitally important role in balancing mitochondrial ROS production in the endothelium. PMID- 27386941 TI - Vascular Inflammation Evaluated by [18F]-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography Is Associated With Endothelial Dysfunction. AB - OBJECTIVE: Endothelial dysfunction is an initial step in atherosclerotic cardiovascular disease. However, involvement of vascular inflammation in endothelial dysfunction is not fully investigated in humans because of the lack of diagnostic modality to noninvasively evaluate vascular inflammation. We assessed the relationship between endothelial function and vascular inflammation evaluated by [(18)F]-fluorodeoxyglucose-positron emission tomography/computed tomographic imaging. APPROACH AND RESULTS: We examined endothelial function and vascular inflammation by flow-mediated dilation (FMD) of the brachial artery and [(18)F]-fluorodeoxyglucose-positron emission tomography/computed tomographic imaging of carotid arteries, respectively, in 145 subjects (95 men and 50 women; mean age, 61.8+/-9.5 years) who underwent a risk-screening test for cardiovascular disease in Kurume University Hospital. Vascular inflammation was measured by blood-normalized standardized uptake value, known as a target:background ratio (TBR). We investigated whether absolute changes from baseline of %FMD after antihypertensive treatment for 6 months (Delta%FMD) were correlated with those of TBR in 33 drug-naive patients with essential hypertension. Multiple logistic regression analysis revealed that age (odds ratio, 1.767 for 10-year increase), male sex (odds ratio, 0.434), low-density lipoprotein-cholesterol (odds ratio, 1.630 for 26-mg/dL increase), and TBR values (odds ratio, 1.759 for 0.2 increase) were independently associated with %FMD in 145 patients. There was an inverse correlation between Delta%FMD and DeltaTBR; DeltaTBR was a sole independent associate of Delta%FMD in hypertensive patients (r=-0.558; P<0.001). CONCLUSIONS: The present study showed that vascular inflammation in the carotid arteries evaluated by [(18)F]-fluorodeoxyglucose positron emission tomography/computed tomography was one of the independent correlates of decreased %FMD, thus suggesting the association of vascular inflammation with endothelial dysfunction in humans. PMID- 27386942 TI - Vision-targeted health related quality of life in older adults: patient-reported visibility problems in low luminance activities are more likely to decline than daytime activities. AB - BACKGROUND: Commonly used vision-targeted health-related quality of life questionnaires almost exclusively focus items on vision under daytime conditions. Older adults even when in good eye health frequently report experiencing vision problems at night and under low environmental light levels, and psychophysical studies also document these visibility problems. Here we compare the progression of self-reported low luminance visibility problems and self-reported visibility problems under daytime conditions in older adults. METHODS: Trained interviewers administered two questionnaires to older adults in normal eye health: the National Eye Institute Visual Function Questionnaire - 25 (NEI VFQ-25) where items are almost entirely focused on difficulties in daytime activities, and the Low Luminance Questionnaire (LLQ) where items are focused on difficulties seeing at night and under low luminance conditions. The following visual functions were also measured: visual acuity, low luminance visual acuity, low luminance deficit, contrast sensitivity, light sensitivity in the macula, and rod-mediated dark adaptation. The protocol was repeated 3 years later. RESULTS: Scores on the NEI VFQ-25 composite and its subscales were unchanged between baseline and 3-year follow-up, whereas scores on the LLQ composite and 5 of 6 subscales significantly decreased (corresponding to less functionality) at the 3-year follow-up. Participants were more likely to display a >= 5 point decrease on the LLQ composite than on the NEI VFQ-25 over 3 years. Visual functional tests were largely unrelated to changes in NEI VFQ-25 and LLQ scores from baseline to follow up. CONCLUSIONS: Older adults' vision-targeted quality of life as measured by questionnaire is more likely to exhibit a practically significant decrease over 3 years using a questionnaire that focused on low luminance activities (LLQ) than one focused on daytime activities (NEI VFQ-25). That the results of visual functional testing did not correspond to older adults' decline in self-reported problems in low luminance activities emphasizes the importance of questionnaires in understanding visual difficulties from the patients' own perspective. PMID- 27386943 TI - Objectively recorded physical activity in pregnancy and postpartum in a multi ethnic cohort: association with access to recreational areas in the neighbourhood. AB - BACKGROUND: Physical activity may reduce the risk of adverse pregnancy outcomes; however, compared to non-pregnant women, a lower proportion of pregnant women meet the physical activity guidelines. Our objectives were to explore overall changes and ethnic differences in objectively recorded moderate-to-vigorous intensity physical activity (MVPA) during pregnancy and postpartum and to investigate the associations with objective and perceived access to recreational areas. METHODS: We analysed 1,467 person-observations from 709 women in a multi ethnic population-based cohort, with MVPA data recorded with the SenseWearTM Pro(3) Armband in early pregnancy (mean gestational week (GW) 15), mid-pregnancy (mean GW 28) and postpartum (mean postpartum week 14). MVPA was limited to bouts >=10 min. Women were nested within 56 neighbourhoods defined by postal code area. We derived neighbourhood-level objective access to recreational areas (good vs limited) by geographic information systems. We collected information about perceived access (high vs low perception) to recreational areas in early pregnancy. We treated ethnicity, objective and perceived access as explanatory variables in separate models based on linear mixed effects regression analyses. RESULTS: Overall, MVPA dropped between early and mid-pregnancy, followed by an increase postpartum. Western women performed more MVPA than women in other ethnic groups across time points, but the differences increased postpartum. Women residing in neighbourhoods with good objective access to recreational areas accumulated on average nine additional MVPA minutes/day (p < 0.01) compared with women in neighbourhoods with limited access. Women with perceptions of high access to recreational areas accumulated on average five additional MVPA minutes/day (p < 0.01) compared with women with perceptions of low access. After mutual adjustments, perceived and objective access to recreational areas remained significantly associated with MVPA. The association between MVPA and access to recreational areas did not differ by time point, ethnic group or socio-economic position. CONCLUSIONS: In all ethnic groups, we observed a decline in MVPA between early and mid-pregnancy. However, at both time points during pregnancy, and especially three months postpartum, Western women were more physically active than ethnic minority women. In all ethnic groups, and at all three time points, both objective and perceived access to recreational areas were positively associated with MVPA levels. PMID- 27386944 TI - Self-assembly of Ni-NTA-modified beta-annulus peptides into artificial viral capsids and encapsulation of His-tagged proteins. AB - beta-Annulus peptides bearing Cys at the N-terminal from tomato bushy stunt virus were synthesised using a standard Fmoc-protected solid-phase method, and the peptide was modified with Ni-NTA at the N-terminal. The Ni-NTA-modified beta annulus peptide self-assembled into virus-like nanocapsules of approximately 40 nm in diameter. The critical aggregation concentration of these nanocapsules in 10 mM Tris-HCl buffer (pH 7.3) at 25 degrees C was 0.053 MUM, which is 470 times lower than that of unmodified beta-annulus peptides. Moreover, size exclusion chromatography of the peptide assembly indicated encapsulation of His-tagged green fluorescent protein in the Ni-NTA-modified artificial viral capsid. PMID- 27386945 TI - Institutional delivery and postnatal care services utilizations in Abuna Gindeberet District, West Shewa, Oromiya Region, Central Ethiopia: A Community based cross sectional study. AB - BACKGROUND: Delivery at health institutions under the care of trained health-care providers and utilization of postnatal cares services plays vital roles in promoting child survival and reducing the risk of maternal mortality. More than 80 % of maternal deaths can be prevented if pregnant women access to essential maternity cares like antenatal care, institutional delivery and postnatal care services. Thus, this study aimed to assess institutional delivery and postnatal care services utilizations in Abuna Gindeberet District, West Shewa, Oromiya Regional State, Ethiopia. METHODS: A community-based cross-sectional study design was employed among 703 randomly identified mothers of Abuna Gindeberet district in March, 2013. Data were collected through interviewer-administered questionnaires and analyzed using SPSS version 16.0. Descriptive, bivariate and multivariate analyses were used to determine prevalence and to identify associated factors with institutional delivery and postnatal care, considering p value of less than 0.05 as significant. The results were presented in a narrative forms, tables and graphs. RESULTS: One hundred one (14.4 %) of mothers gave birth to their last baby in health institutions. From 556 (79.1 %) of respondents who heard about postnatal care services, only 223 (31.7 %) of them utilized postnatal care services for their recent childbirth. From the total postnatal care users, 204 (91.5 %) of them took the services from health extension workers. Decision making styles, household distances from health institutions, household being model family and ANC services utilizations were found to be statistically significant with both institutional delivery and postnatal care services utilizations. But educational status of husbands was statistically significant with only postnatal care services utilizations. CONCLUSIONS: Both institutional delivery and postnatal care services utilizations from health institutions were low. Decision-making styles, household distances from health institutions, household being model family and ANC services utilizations were the common factors that affect institutional delivery and postnatal care services utilizations from health institutions. Therefore, giving attention to the identified factors could improve and sustain institutional delivery and postnatal care services utilizations from health institutions. PMID- 27386946 TI - Hominis Placenta facilitates hair re-growth by upregulating cellular proliferation and expression of fibroblast growth factor-7. AB - BACKGROUND: Hominis Placenta (HP) known as a restorative medicine in Traditional Chinese Medicine (TCM), has been widely applied in the clinics of Korea and China as an anti-aging agent to enhance the regeneration of tissue. This study was conducted to investigate whether topical treatment of HP promotes hair regrowth in the animal model. METHODS: The dorsal hairs of 8-week-old C57BL/6 mice were depilated to synchronize hair follicles to the anagen phase. HP was applied topically once a day for 15 days. Hair growth was evaluated visually and microscopically. The incorporation of bromodeoxyuridine (BrdU) and expression of proliferating cell nuclear antigen (PCNA), fibroblast growth factor-7 (FGF-7) in dorsal skin tissue was examined by immunohistochemical analysis. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure the mRNA expression of FGF-7. RESULTS: HP exhibited potent hair growth-promoting activity in C57BL/6 mice. Gross examination indicated that HP markedly increased hair regrowth as well as hair density and diameter. Histologic analysis showed that HP treatment enhanced the anagen induction of hair follicles. Immunohistochemical analysis revealed that BrdU incorporation and the expressions of PCNA were increased by treatment of HP. HP treatment significantly increased the expression of FGF-7, which plays pivotal roles to maintain anagen phase both protein and mRNA levels. CONCLUSIONS: Taken together, our results indicate that HP has a potent hair growth-promoting activity; therefore, it may be a good candidate for the treatment of alopecia. PMID- 27386947 TI - Isoform D of vascular endothelial growth factor in systemic capillary leak syndrome: a case report. AB - BACKGROUND: Systemic capillary leak syndrome is a rare condition characterized by episodic attacks of hypovolemia due to systemic capillary hyperpermeability, which results in profound hypotension and edema. Although the implication of vascular endothelial growth factor, angiopoietin-2, and C-X-C motif chemokine 10 has been suggested, the pathogenesis of systemic capillary leak syndrome remains unclear. In this report, we describe a case of systemic capillary leak syndrome in which serum isoform D of vascular endothelial growth factor was elevated. To the best of our knowledge, this is the first reported case of systemic capillary leak syndrome in which isoform D of vascular endothelial growth factor is suggested as the plausible biomarker. CASE PRESENTATION: A 41-year-old Japanese man was transferred to our emergency department. He was hypotensive, tachycardic, and edematous over the trunk and all four limbs. He received aggressive intravenous fluid therapy and underwent fasciotomy of the right forearm to prevent muscle necrosis. A diagnosis of systemic capillary leak syndrome was suspected. The presence of serum monoclonal immunoglobulin G and kappa light chain supported this diagnosis. Prevention of hypotensive crises was unsuccessfully attempted with theophylline, intravenous immunoglobulin, high-dose dexamethasone, bortezomib, melphalan, and prednisolone; however, the patient's attacks dramatically disappeared after the introduction of thalidomide. The serum of the patient was stored soon after the onset of hypotensive crisis and analyzed to profile possible mediators responsible for the capillary leak. The concentration of vascular endothelial growth factor, angiopoietin-2, and C-X-C motif chemokine 10 were all within normal ranges. Meanwhile, we found that isoform D of vascular endothelial growth factor was elevated, which was normalized after the introduction of thalidomide. CONCLUSIONS: In our patient, isoform D of vascular endothelial growth factor (instead of vascular endothelial growth factor) may have been a causative factor of hypotensive crises, since isoform D contributes to vascular endothelial growth factor receptor-2 signaling, which is the major mediator of the permeability-enhancing effects of vascular endothelial growth factor. We suggest the measurement of isoform D of vascular endothelial growth factor in patients with systemic capillary leak syndrome in whose serum vascular endothelial growth factor is not elevated. PMID- 27386948 TI - Increased neutrophil-to-lymphocyte ratio is associated with disease-specific mortality in patients with penile cancer. AB - BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a simple marker of the systemic inflammatory response, has been demonstrated to correlate with patient outcomes for various solid malignancies. We investigated the utility of the pretreatment NLR as a prognosticator in patients who presented with penile cancer. METHODS: A total of 41 patients who underwent complete blood count with differential and subsequent radical penectomy from 1988 to 2014 were analyzed. We assessed the correlation between the NLR and the prognosis of penile cancer. RESULTS: The median and mean (+/- SD) NLRs in 41 penile cancer patients were 3.42 and 5.03 +/- 4.99, respectively. Based on the area under receiver operator characteristic curve, the cut-off value of NLR was determined to be 2.82. Patients with a high NLR (>=2.82) showed a significantly poorer cancer-specific survival (p = 0.023) than those with a low NLR. CONCLUSIONS: The pretreatment NLR may function as a biomarker that precisely predicts the prognosis in patients with penile cancer. PMID- 27386949 TI - Widespread parainflammation in human cancer. AB - BACKGROUND: Chronic inflammation has been recognized as one of the hallmarks of cancer. We recently showed that parainflammation, a unique variant of inflammation between homeostasis and chronic inflammation, strongly promotes mouse gut tumorigenesis upon p53 loss. Here we explore the prevalence of parainflammation in human cancer and determine its relationship to certain molecular and clinical parameters affecting treatment and prognosis. RESULTS: We generated a transcriptome signature to identify parainflammation in many primary human tumors and carcinoma cell lines as distinct from their normal tissue counterparts and the tumor microenvironment and show that parainflammation positive tumors are enriched for p53 mutations and associated with poor prognosis. Non-steroidal anti-inflammatory drug (NSAID) treatment suppresses parainflammation in both murine and human cancers, possibly explaining a protective effect of NSAIDs against cancer. CONCLUSIONS: We conclude that parainflammation, a low-grade form of inflammation, is widely prevalent in human cancer, particularly in cancer types commonly harboring p53 mutations. Our data suggest that parainflammation may be a driver for p53 mutagenesis and a guide for cancer prevention by NSAID treatment. PMID- 27386950 TI - The health and well-being of men who have sex with men (MSM) in Britain: Evidence from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). AB - BACKGROUND: To date, research on men who have sex with men (MSM) has largely focused on their sexual health needs and on men recruited from gay-orientated venues. National probability survey data provide a rare opportunity to examine the broader sociodemographic, behavioural, and health profiles of MSM, defined as men who reported >=1 male sexual partner(s) in the past 5 years, and thus regardless of their sexual identity, in comparison to men reporting sex exclusively with women (MSEW) during this time, and also the extent that health inequalities cluster. METHODS: Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a probability sample survey, interviewed 15,162 people aged 16-74 years (6,293 men) during 2010-2012 using computer assisted personal-interviewing with a computer-assisted self-interview. We used multivariable regression to compare MSM relative to MSEW in their reporting of variables, individually and collectively, corresponding to three domains: physical, mental, and sexual health. RESULTS: Among all men, 2.6 % (n = 190) were defined as MSM, of whom 52.5 % (95 % CI: 43.6 %-61.2 %) identified as gay. MSM were as likely as MSEW (n = 5,069) to perceive their health was 'bad'/'very bad', despite MSM being more likely to report a long-standing illness/disability/infirmity (adjusted odds ratio, AOR: 1.46, 95 % CI:1.02-2.09), treatment for depression/past year (2.75, 1.69-4.47), and substance use (e.g., recreational drug use/past year: 3.46, 2.22-5.40). MSM were more likely to report harmful sexual health behaviours, e.g., condomless sex with >=2 partners/past year (3.52, 2.13-5.83), and poor sexual health outcomes, including STI diagnosis/es (5.67, 2.67-12.04), poorer sexual function (2.28, 1.57-3.33), both past year, and ever-experience of attempted non-volitional sex (6.51, 4.22 10.06). MSM were also more likely than MSEW to report poor health behaviours and outcomes both within and across the three health domains considered. Of all MSM, 8.4 % had experienced poor health outcomes in all three domains - physical, mental, and sexual health - in contrast to 1.5 % of all MSEW. CONCLUSIONS: MSM are disproportionately affected by a broad range of harmful health behaviours and poor health outcomes. Although often observed for a minority of MSM, many health inequalities were seen in combination such that policies and practices aimed at improving the health and well-being of MSM require a holistic approach, regardless of clinical specialty. PMID- 27386951 TI - From Ewald sphere to Ewald shell in nonlinear optics. AB - Ewald sphere is a simple vector scheme to depict the X-ray Bragg diffraction in a crystal. A similar method, known as the nonlinear Ewald sphere, was employed to illustrate optical frequency conversion processes. We extend the nonlinear Ewald sphere to the Ewald shell construction. With the Ewald shell, a variety of quasi phase-matching (QPM) effects, such as the collective envelope effect associated with multiple QPM resonances, the enhanced second- harmonic generation due to multiple reciprocal vectors etc., are suggested theoretically and verified experimentally. By rotating the nonlinear photonic crystal sample, the dynamic evolution of these QPM effects has also been observed, which agreed well with the Ewald shell model. PMID- 27386952 TI - A review of carrier thermoelectric-transport theory in organic semiconductors. AB - Carrier thermoelectric-transport theory has recently become of growing interest and numerous thermoelectric-transport models have been proposed for organic semiconductors, due to pressing current issues involving energy production and the environment. The purpose of this review is to provide a theoretical description of the thermoelectric Seebeck effect in organic semiconductors. Special attention is devoted to the carrier concentration, temperature, polaron effect and dipole effect dependence of the Seebeck effect and its relationship to hopping transport theory. Furthermore, various theoretical methods are used to discuss carrier thermoelectric transport. Finally, an outlook of the remaining challenges ahead for future theoretical research is provided. PMID- 27386953 TI - Prioritization of treatments for lower extremity peripheral artery disease in low and middle-income countries. AB - INTRODUCTION: Lower extremity peripheral artery disease (PAD) is increasing in prevalence in low- and middle-income countries creating a large health care burden. Clinical management may require substantial resources but little consideration has been given to which treatments are appropriate for less advantaged countries. EVIDENCE ACQUISITION: The aim of this review was to systematically appraise published data on the costs and effectiveness of PAD treatments used commonly in high-income countries, and for an international consensus panel to review that information and propose a hierarchy of treatments relevant to low- and middle-income countries. EVIDENCE SYNTHESIS: Pharmacotherapy for intermittent claudication was found to be expensive and improve walking distance by a modest amount. Exercise and endovascular therapies were more effective and exercise the most cost-effective. For critical limb ischemia, bypass surgery and endovascular therapy, which are both resource intensive, resulted in similar rates of amputation-free survival. Substantial reductions in cardiovascular events occurred with use of low cost drugs (statins, ACE inhibitors, anti-platelets) and smoking cessation. CONCLUSIONS: The panel concluded that, in low- and middle-income countries, cardiovascular prevention is a top priority, whereas a lower priority should be given to pharmacotherapy for leg symptoms and revascularisation, except in countries with established vascular units. PMID- 27386954 TI - Integrated network-diversity analyses suggest suppressive effect of Hodgkin's lymphoma and slightly relieving effect of chemotherapy on human milk microbiome. AB - We aim to investigate the effects of Hodgkin's lymphoma and the chemotherapy for treating the disease on the human milk microbiome through integrated network and community diversity analyses. Our analyses suggest that Hodgkin's lymphoma seems to have a suppressing effect on the milk microbiome by lowering the milk microbial community diversity, as measured by the Hill numbers profiles. Although the diversity analysis did not reveal an effect of chemotherapy on community diversity, bacterial species interaction network analysis shows that chemotherapy may help to slightly restore the milk microbiome impacted by Hodgkin's lymphoma through its influence on the interactions among species (or OTUs). We further constructed diversity-metabolites network, which suggests that the milk microbial diversity is positively correlated with some beneficial milk metabolites such as DHA (DocosaHexaenoic Acid), and that the diversity is negatively correlated with some potentially harmful metabolites such as Butanal. We hence postulate that higher milk microbial diversity should be a signature of healthy mothers and beneficial to infants. Finally, we constructed metabolites OTU correlation networks, from which we identified some special OTUs. These OTUs deserve further investigations given their apparent involvements in regulating the levels of critical milk metabolites such as DHA, Inositol and Butanal. PMID- 27386956 TI - Subsurface to substrate: dual-scale micro/nanofluidic networks for investigating transport anomalies in tight porous media. AB - Micro/nanofluidic experiments in synthetic representations of tight porous media, often referred to as "reservoir-on-a-chip" devices, are an emerging approach to researching anomalous fluid transport trends in energy-bearing and fluid sequestering geologic porous media. We detail, for the first time, the construction of dual-scale micro/nanofluidic devices that are relatively large scale, two-dimensional network representations of granular and fractured nanoporous media. The fabrication scheme used in the development of the networks on quartz substrates (master patterns) is facile and replicable: transmission electron microscopy (TEM) grids with lacey carbon support film were used as shadow masks in thermal evaporation/deposition and reactive ion etch (RIE) was used for hardmask pattern transfer. The reported nanoscale network geometries are heterogeneous and composed of hydraulically resistive paths (throats) meeting at junctures (pores) to mimic the low topological connectivity of nanoporous sedimentary rocks such as shale. The geometry also includes homogenous microscale grid patterns that border the nanoscale networks and represent microfracture pathways. Master patterns were successfully replicated with a sequence of polydimethylsiloxane (PDMS) and Norland Optical Adhesive (NOA) 63 polymers. The functionality of the fabricated quartz and polymer nanofluidic devices was validated with aqueous imbibition experiments and differential interference contrast microscopy. These dual-scale fluidic devices are promising predictive tools for hypothesis testing and calibration against bulk fluid measurements in tight geologic, biologic, and synthetic porous material of similar dual-scale pore structure. Applications to shale/mudrock transport studies in particular are focused on herein. PMID- 27386955 TI - CpsR, a GntR family regulator, transcriptionally regulates capsular polysaccharide biosynthesis and governs bacterial virulence in Streptococcus pneumoniae. AB - Transcriptional regulation of capsule expression is critical for pneumococcal transition from carriage to infection, yet the underlying mechanism remains incompletely understood. Here, we describe the regulation of capsular polysaccharide, one of the most important pneumococcal virulence factor by a GntR family regulator, CpsR. Electrophoretic mobility-shift assays have shown the direct interaction between CpsR and the cps promoter (cpsp), and their interaction could be competitively interfered by glucose. DNase I footprinting assays localized the binding site to a region -146 to -114 base pairs relative to the transcriptional start site of the cps locus in S. pneumoniae D39. We found that CpsR negatively controlled the transcription of the cps locus and hence CPS production, which was confirmed by fine-tuning expression of CpsR in a DeltacpsR complemented strain. Increased expression of CpsR in complemented strain led to a decreased resistance to the whole-blood-mediated killing, suggesting a protective role for CpsR-cpsp interaction in the establishment of invasive infection. Finally, animal experiments showed that CpsR-cpsp interaction was necessary for both pneumococcal colonization and invasive infection. Taken together, our results provide a thorough insight into the regulation of capsule production mediated by CpsR and its important roles in pneumococcal pathogenesis. PMID- 27386957 TI - Local food web management increases resilience and buffers against global change effects on freshwaters. AB - A major challenge for ecological research is to identify ways to improve resilience to climate-induced changes in order to secure the ecosystem functions of natural systems, as well as ecosystem services for human welfare. With respect to aquatic ecosystems, interactions between climate warming and the elevated runoff of humic substances (brownification) may strongly affect ecosystem functions and services. However, we hitherto lack the adaptive management tools needed to counteract such global-scale effects on freshwater ecosystems. Here we show, both experimentally and using monitoring data, that predicted climatic warming and brownification will reduce freshwater quality by exacerbating cyanobacterial growth and toxin levels. Furthermore, in a model based on long term data from a natural system, we demonstrate that food web management has the potential to increase the resilience of freshwater systems against the growth of harmful cyanobacteria, and thereby that local efforts offer an opportunity to secure our water resources against some of the negative impacts of climate warming and brownification. This allows for novel policy action at a local scale to counteract effects of global-scale environmental change, thereby providing a buffer period and a safer operating space until climate mitigation strategies are effectively established. PMID- 27386958 TI - Application of nanodisc technology for direct electrochemical investigation of plant cytochrome P450s and their NADPH P450 oxidoreductase. AB - Direct electrochemistry of cytochrome P450 containing systems has primarily focused on investigating enzymes from microbes and animals for bio-sensing applications. Plant P450s receive electrons from NADPH P450 oxidoreductase (POR) to orchestrate the bio-synthesis of a plethora of commercially valuable compounds. In this report, full length CYP79A1, CYP71E1 and POR of the dhurrin pathway in Sorghum bicolor were reconstituted individually in nanoscale lipid patches, "nanodiscs", and directly immobilized on unmodified gold electrodes. Cyclic voltammograms of CYP79A1 and CYP71E1 revealed reversible redox peaks with average midpoint potentials of 80 +/- 5 mV and 72 +/- 5 mV vs. Ag/AgCl, respectively. POR yielded two pairs of redox peaks with midpoint potentials of 90 +/- 5 mV and -300 +/- 10 mV, respectively. The average heterogeneous electron transfer rate constant was calculated to be ~1.5 s(-1). POR was electro catalytically active while the P450s generated hydrogen peroxide (H2O2). These nanodisc-based investigations lay the prospects and guidelines for construction of a simplified platform to perform mediator-free, direct electrochemistry of non engineered cytochromes P450 under native-like conditions. It is also a prelude for driving plant P450 systems electronically for simplified and cost-effective screening of potential substrates/inhibitors and fabrication of nano-bioreactors for synthesis of high value natural products. PMID- 27386959 TI - Pharmacokinetic Considerations in Designing Pediatric Studies of Proteins, Antibodies, and Plasma-Derived Products. AB - Ignoring the principles of pediatric pharmacology can have serious consequences. Therefore, it is necessary to understand and recognize the impact of developmental processes in children. It is now well recognized that age and the disease state can alter the pharmacokinetics (PKs) of a drug, as a result adjustment in dosing regimen in children as compared with the adults is essential. This review emphasizes on the importance of PK studies in pediatric population for macromolecules. Macromolecules differ from small molecules in many respects, and it is necessary to have a thorough understanding of the behavior of macromolecules in the body across different age groups. The review highlights that like small molecules, the PKs of macromolecules in pediatric population also differ from adults, hence, a PK study is essential in pediatrics for appropriate dose selection in this population. The review also takes a critical look on the many extrapolation techniques to predict PK parameters in pediatrics from adult data. PMID- 27386960 TI - Broad-Spectrum Beta-Lactams for Patients Allergic to Penicillin. PMID- 27386961 TI - The Discovery of Statins. PMID- 27386962 TI - Resistance Training Priming Activity Improves Upper-Body Power Output in Rugby Players: Implications for Game Day Performance. AB - Mason, BRJ, Argus, CK, Norcott, B, and Ball, NB. Resistance training priming activity improves upper-body power output in rugby players: implications for game day performance. J Strength Cond Res 31(4): 913-920, 2017-"Priming" or preactivation strategies performed in the hours leading into competition have been suggested to improve game day performance. Therefore, this study assessed the effectiveness of a resistance training priming activity on eliciting changes in lower- and upper-body power output, along with perceptual measures. To assess these changes, 13 state-level rugby players (aged 18.5 +/- 0.5 years) completed a test-retest protocol using a counterbalanced crossover design. Perceptual (readiness to perform questionnaire) and performance measures (20-kg countermovement jump [CMJ], 20-kg bench throw) were completed before either a control (rest) or priming activity (4 sets of 3 banded back squats and banded bench press). After a 1-hour and 45-minute recovery period, perceptual and performance measures were repeated. Readiness to perform showed no meaningful differences pre- and postintervention. Bench throw peak power (8.5 +/- 5.8%, 90% confidence limit; p <= 0.05) improved after the priming activity when compared with the control trial. Countermovement jump peak power (3.4 +/- 4.9%; p > 0.05) had a small decrease after the priming activity when compared with the control trial. Therefore, completing a priming activity 1 hour and 45 minutes before competition is recommended to improve upper-body power output. However, further research into lower-body priming protocols should be conducted before implementing a lower-body priming activity before competition. PMID- 27386963 TI - Effects of Energy Drinks on Economy and Cardiovascular Measures. AB - Peveler, WW, Sanders, GJ, Marczinski, CA, and Holmer, B. Effects of energy drinks on economy and cardiovascular measures. J Strength Cond Res 31(4): 882-887, 2017 The use of energy drinks among athletes has risen greatly. Caffeine and taurine are the 2 primary performance enhancing ingredients found in energy drinks. The number of emergency department visits involving energy drinks doubled over the past 5 years. Reviews of the health complications have highlighted adverse cardiovascular events. The literature reveals that caffeine is known to moderately increase blood pressure (BP) and heart rate (HR). The purpose of this study was to determine the effect of 3 different energy drinks on cardiovascular and performance measures. Fifteen recreational runners completed 5 trials. The first trial consisted of a graded exercise protocol. The 4 remaining trials consisted of 15-minute economy trials at a treadmill speed consistent with 70% of subject's V[Combining Dot Above]O2max. An hour before subjects ingested 1 of the 3 energy drinks or a placebo. HR, BP, V[Combining Dot Above]O2, and rating of perceived exertion (RPE) were recorded during the 15-minute trial. Mean values for dependent measures were compared using repeated-measures analysis of variance. Fifteen-minute systolic BP readings were significantly lower in the placebo trials (156.93 +/- 15.50) in relation to the 3 energy drink trials (163.87 +/- 13.30, 166.47 +/- 13.71, and 165.00 +/- 15.23). There were no significant differences in diastolic BP and HR. There were no significant differences found in V[Combining Dot Above]O2 or RPE measures. Ingestion of energy drinks demonstrated no change in V[Combining Dot Above]O2 or RPE during the economy trials. The findings show no performance benefits under the conditions of this study. However, there does appear to be a significant increase in systolic BP. PMID- 27386964 TI - Optimal Loads for Power Differ by Exercise in Older Adults. AB - Potiaumpai, M, Gandia, K, Rautray, A, Prendergast, T, and Signorile, JF. Optimal loads for power differ by exercise in older adults. J Strength Cond Res 30(10): 2703-2712, 2016-Power training in older adults has been shown to increase muscle strength, power, and physical function, and decrease the risk of falls and related injuries. Although there are clear indications that optimal loads for power vary due to biomechanical factors, no studies have attempted to determine the optimal loads for specific exercises used to improve muscle power. Using the load that maximizes power output for individual exercises can maximize power gains, improve training efficiency, and augment gains in physical function. Seventy community-dwelling older adults (age = 70.5 +/- 5.7 years) participated in strength and power testing during 2 sessions, each lasting for 1.5 hours. Participants were tested on 6 different pneumatic resistance machines to determine their one repetition maximum (1RM) and power. Power testing was performed at loads between 30 and 90% of each participant's 1RM. For the chest press and seated row, the optimal load range was between 40 and 60% 1RM, with peak power at 50% (p < 0.001) for both machines. The LAT pull-down optimal load range was between 30 and 50%, with peak power occurring at 40% (p < 0.001). The leg curl and leg press optimal load range was between 50 and 70%, with peak power occurring at 60% (p < 0.001). Peak power for the calf raise occurred at 60% (p < 0.001). We conclude that different exercise movements require the use of different optimal load ranges to maximize muscle power in older persons. PMID- 27386965 TI - Metagenomic Analysis of Sputum Microbiome as a Tool toward Culture-Independent Pathogen Detection of Patients with Ventilator-associated Pneumonia. PMID- 27386967 TI - Pediatric dermatology: advancement in management and targeted therapy. PMID- 27386966 TI - Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports Frizzled 7 trafficking and signalling. AB - PDZ domain-containing proteins work as intracellular scaffolds to control spatio temporal aspects of cell signalling. This function is supported by the ability of their PDZ domains to bind other proteins such as receptors, but also phosphoinositide lipids important for membrane trafficking. Here we report a crystal structure of the syntenin PDZ tandem in complex with the carboxy-terminal fragment of Frizzled 7 and phosphatidylinositol 4,5-bisphosphate (PIP2). The crystal structure reveals a tripartite interaction formed via the second PDZ domain of syntenin. Biophysical and biochemical experiments establish co operative binding of the tripartite complex and identify residues crucial for membrane PIP2-specific recognition. Experiments with cells support the importance of the syntenin-PIP2 interaction for plasma membrane targeting of Frizzled 7 and c-jun phosphorylation. This study contributes to our understanding of the biology of PDZ proteins as key players in membrane compartmentalization and dynamics. PMID- 27386969 TI - Blistering diseases in neonates. AB - PURPOSE OF REVIEW: Neonatal blistering diseases are rare yet potentially fatal. Therefore, it is crucial for clinicians to know its broad range of differential diagnoses. This review discusses the recent literature on the causes and the most appropriate clinical approach to neonatal blistering diseases. RECENT FINDINGS: Neonatal infections are the commonest causes for neonatal blistering. On the other hand, autoimmune blistering diseases are extremely rare with the literature limited to case reports and one systematic review only. Inherited genodermatoses are also rare, with recent developments in epidermolysis bullosa classification. SUMMARY: In conclusion, as neonatal infections are the commonest cause for blistering, any neonate with blistering should have their blister fluid investigated for infection, while an antimicrobial should be initiated early. Autoimmune blistering diseases should be considered in neonates with a maternal history of autoimmune blistering disease. Although pemphigus and bullous pemphigoid have overall good prognoses, linear IgA bullous dermatoses has a poor prognosis and requires aggressive treatment. Inherited genodermatoses should be suspected when there is a family history of genodermatoses or consanguinity. In this case, the clinician should not hesitate to seek dermatology advice, perform a skin biopsy and consider genetic testing. PMID- 27386970 TI - Advancement in management of epidermolysis bullosa. AB - PURPOSE OF REVIEW: Epidermolysis bullosa is a hereditary skin disorder characterized by skin fragility. However, the disease can manifest in many different organ systems, therefore children born with epidermolysis bullosa may have life long, complex medical needs. In this review, we will use a system-based approach to highlight important aspects of disease management and recent advancements in each of the areas. In addition, we will overview some of the cutting edge therapeutic developments in epidermolysis bullosa. RECENT FINDINGS: Recent advancements in supportive care of epidermolysis bullosa with focus on wound, pain, pruritus and nutrition status were discussed. Clinical surveillance and complication prevention are critical to improve clinical outcomes. Generalized epidermolysis bullosa is a systemic disease with increased morbidity and mortality; therefore, complex care using a multidisciplinary approach will provide the greatest benefits for patients. Current targeted treatments for epidermolysis bullosa aim at restoring the skin integrity using protein, cell, and gene therapies. SUMMARY: Improvement in care of epidermolysis bullosa in recent years results from keen clinical observation, novel molecular targeting, and the embracement of translational research. PMID- 27386968 TI - Immunogenetics of cutaneous lupus erythematosus. AB - PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) is the prototypic autoimmune condition, often affecting multiple organ systems, including the skin. Cutaneous lupus erythematosus (CLE) is distinct from SLE and may be skin limited or associated with systemic disease. Histopathologically, the hallmark of lupus specific manifestations of SLE and CLE is an interface dermatitis. The cause of SLE and CLE is likely multifactorial and may include shared genetic factors. In this review, we will discuss the genetic findings related to the cutaneous manifestations of SLE and isolated CLE, with a particular focus on the lupus specific CLE subtypes. RECENT FINDINGS: Several major histocompatibility complex and nonmajor histocompatibility complex genetic polymorphisms have been identified which may contribute to the cutaneous manifestations of SLE and to CLE. Most of these genetic variants are associated with mechanisms attributed to the pathogenesis of SLE, including pathways involved in interferon and vitamin D regulation and ultraviolet light exposure. Although there is overlap between the genetic factors associated with SLE and CLE, there appear to be unique genetic factors specific for CLE. SUMMARY: Improved understanding of the genetics of CLE may lead to the creation of targeted therapies, improving outcomes for patients with this challenging dermatologic condition. PMID- 27386971 TI - Endocrinology and metabolism 2016. PMID- 27386972 TI - New clinical and molecular insights into Silver-Russell syndrome. AB - PURPOSE OF REVIEW: The purpose of review is to summarize new outcomes for the clinical characterization, molecular strategies, and therapeutic management of Silver-Russell syndrome (SRS). RECENT FINDINGS: Various teams have described the clinical characteristics of SRS patients by genotype. A clinical score for the definition of SRS and for orienting molecular investigations has emerged. Insulin like growth factor 2 (a major fetal growth factor) has been implicated in the pathophysiology of SRS, as the principle molecular mechanism underlying the disease is loss of methylation of the 11p15 region, including the imprinted insulin-like growth factor 2 gene. Maternal uniparental disomy of chromosome 7 and recently identified rare molecular defects have also been reported in patients with SRS. However, 40% of patients still have no molecular diagnosis. SUMMARY: The definition of SRS has remained clinical since the first description of this condition, despite the identification of various molecular causes. The clinical issues faced by these patients are similar to those faced by other patients born small for gestational age (SGA), but patients with SRS require specific multidisciplinary management of their nutrition, growth, and metabolism, as they usually present an extreme form of SGA. Molecular analyses can confirm SRS, and are of particular importance for genetic counseling and prenatal testing. PMID- 27386973 TI - Pituitary stalk interruption syndrome: cause, clinical manifestations, diagnosis, and management. AB - PURPOSE OF REVIEW: Pituitary stalk interruption syndrome (PSIS) is characterized by a thin or absent pituitary stalk, hypoplasia of the adenohypophysis, and ectopic neurohypophysis. PSIS manifestations include a wide spectrum of clinical phenotypes and pituitary hormone deficiencies of variable degree and timing of onset. In this review, recent advances with respect to the cause of PSIS, clinical characteristics leading to earlier diagnosis, and management are outlined. RECENT FINDINGS: Diagnosis of PSIS is often delayed probably because clinical findings such as neonatal hypoglycemia, cholestasis, and/or micropenis as well as decreasing growth velocity are not appropriately and timely validated. Recently, molecular defects in various genes have been associated with PSIS albeit in a small number of cases. These findings suggest that PSIS belongs to the spectrum of holoprosencephaly-related defects. Phenotype-genotype discordance and the existence of asymptomatic carriers of a given molecular aberration indicate that penetrance may be modified favorably or unfavorably by the presence of other genetic and/or environmental factors. SUMMARY: PSIS constitutes an antenatal anatomical defect. Neonatal hypoglycemia, cholestasis, and/or micropenis with or without growth deficit should raise the possibility of combined pituitary hormone deficiency, a life-threatening condition in cases of coexisting cortisol deficiency. It is important to search for molecular defects in all PSIS cases, as precise identification of the cause is a prerequisite for genetic counseling. PMID- 27386974 TI - Control of the onset of puberty. AB - PURPOSE OF REVIEW: The mechanism of puberty initiation remains an enigma, despite extensive research in the field. Pulsatile pituitary gonadotropin secretion under the guidance of hypothalamic gonadotropin-releasing hormone (GnRH) constitutes a sine qua non for pubertal onset. In turn, the secretion of GnRH in the human hypothalamus is regulated by kisspeptin and its receptor as well as by permissive or opposing signals mediated by neurokinin B and dynorphin acting on their respective receptors. These three supra-GnRH regulators compose the Kisspeptin, Neurokinin B and Dynorhin neurons (KNDy) system, a key player in pubertal onset and progression. RECENT FINDINGS: The recent discovery that makorin ring finger protein 3 is also involved in puberty initiation provided further insights into the regulation of the KNDy pathway. In fact, the inhibitory (gamma-amino butyric acid, neuropeptide Y, and RFamide-related peptide-3) and stimulatory signals (glutamate) acting upstream of KNDy called into question the role of makorin ring finger protein 3 as the gatekeeper of puberty. Meanwhile, the findings that 'neuroestradiol' produced locally and endocrine disruptors from the environment may influence GnRH secretion is intriguing. Finally, epigenetic mechanisms have been implicated in pubertal onset through recently discovered mechanisms. SUMMARY: The exact molecular machinery underlying puberty initiation in humans is under intensive investigation. In this review, we summarize research evidence in the field, while emphasizing the areas of uncertainty and underlining the impact of current information on the evolving theory regarding this fascinating phenomenon. PMID- 27386975 TI - Long-term neurodevelopmental benefits of breastfeeding. AB - PURPOSE OF REVIEW: The American Academy of Pediatrics recommends exclusive breastfeeding for the first 6 months of an infant#$#apos;s life, with continuation of breastfeeding for at least a year or as mutually desired by mother and child. A robust body of research literature documenting the short-term medical, developmental, and emotional benefits of breastfeeding for infants and toddlers supports this position. This article reviews the neurodevelopmental benefits of breastfeeding as it relates to preschool and school-age children, with particular emphasis on cognitive development, attention deficit/hyperactivity disorder, and autism spectrum disorder. RECENT FINDINGS: The majority of research studies examining breastfeeding and long-term neurodevelopmental outcomes suggest that children who breastfeed for longer than 6 months have better cognitive outcomes, lower risk of developing attention deficit/hyperactivity disorder, and lower risk of being diagnosed with autism spectrum disorder. SUMMARY: Pediatricians play a critical role in educating and counseling families about infant nutrition and feeding. Along with the many positive short-term medical effects that breastfeeding confers, physicians should be aware of the growing body of research suggesting that there are also significant long-term neurodevelopmental benefits of breastfeeding. PMID- 27386976 TI - The ins and outs of managing avoidance diets for food allergies. AB - PURPOSE OF REVIEW: Food allergic reactions have become more prevalent and management of food allergies requires dietary avoidance of triggers that may place children at nutritional risk. RECENT FINDINGS: Immunoglobulin E and non immunoglobulin E-mediated food allergies lead to dietary avoidance. Although some children outgrow food allergies or become tolerant to cooked/baked versions of the allergen, many do not. Multiple food avoidance increases the risk for inadequate nutrient intake, including protein, calcium, vitamin D, and others. Multidisciplinary management of patients requires careful attention to growth, particularly height, and nutrition. SUMMARY: Although attention to accurate diagnosis of food allergy is key, understanding nutritional risks of children with food allergies can lead to opportunities to address potential deficiencies resulting from food allergen avoidance. PMID- 27386978 TI - A review on sludge dewatering indices. AB - Dewatering of sludge from sewage treatment plants is proving to be a significant challenge due to the large amounts of residual sludges generated annually. In recent years, research and development have focused on improving the dewatering process in order to reduce subsequent costs of sludge management and transport. To achieve this goal, it is necessary to establish reliable indices that reflect the efficiency of sludge dewatering. However, the evaluation of sludge dewaterability is not an easy task due to the highly complex nature of sewage sludge and variations in solid-liquid separation methods. Most traditional dewatering indices fail to predict the maximum cake solids content achievable during full-scale dewatering. This paper reviews the difficulties in assessing sludge dewatering performance, and the main techniques used to evaluate dewatering performance are compared and discussed in detail. Finally, the paper suggests a new dewatering index, namely the modified centrifugal index, which is demonstrated to be an appropriate indicator for estimating the final cake solids content as well as simulating the prototype dewatering process. PMID- 27386977 TI - Titanium peroxide nanoparticles enhanced cytotoxic effects of X-ray irradiation against pancreatic cancer model through reactive oxygen species generation in vitro and in vivo. AB - BACKGROUND: Biological applications of nanoparticles are rapidly increasing, which introduces new possibilities to improve the efficacy of radiotherapy. Here, we synthesized titanium peroxide nanoparticles (TiOxNPs) and investigated their efficacy as novel agents that can potently enhance the effects of radiation in the treatment of pancreatic cancer. METHODS: TiOxNPs and polyacrylic acid modified TiOxNPs (PAA-TiOxNPs) were synthesized from anatase-type titanium dioxide nanoparticles (TiO2NPs). The size and morphology of the PAA-TiOxNPs was evaluated using transmission electron microscopy and dynamic light scattering. The crystalline structures of the TiO2NPs and PAA-TiOxNPs with and without X-ray irradiation were analyzed using X-ray absorption. The ability of TiOxNPs and PAA TiOxNPs to produce reactive oxygen species in response to X-ray irradiation was evaluated in a cell-free system and confirmed by flow cytometric analysis in vitro. DNA damage after X-ray exposure with or without PAA-TiOxNPs was assessed by immunohistochemical analysis of gamma-H2AX foci formation in vitro and in vivo. Cytotoxicity was evaluated by a colony forming assay in vitro. Xenografts were prepared using human pancreatic cancer MIAPaCa-2 cells and used to evaluate the inhibition of tumor growth caused by X-ray exposure, PAA-TiOxNPs, and the combination of the two. RESULTS: The core structures of the PAA-TiOxNPs were found to be of the anatase type. The TiOxNPs and PAA-TiOxNPs showed a distinct ability to produce hydroxyl radicals in response to X-ray irradiation in a dose- and concentration-dependent manner, whereas the TiO2NPs did not. At the highest concentration of TiOxNPs, the amount of hydroxyl radicals increased by >8.5-fold following treatment with 30 Gy of radiation. The absorption of PAA-TiOxNPs enhanced DNA damage and resulted in higher cytotoxicity in response to X-ray irradiation in vitro. The combination of the PAA-TiOxNPs and X-ray irradiation induced significantly stronger tumor growth inhibition compared to treatment with either PAA-TiOxNPs or X-ray alone (p < 0.05). No apparent toxicity or weight loss was observed for 43 days after irradiation. CONCLUSIONS: TiOxNPs are potential agents for enhancing the effects of radiation on pancreatic cancer and act via hydroxyl radical production; owing to this ability, they can be used for pancreatic cancer therapy in the future. PMID- 27386979 TI - Sewage sludge ash characteristics and potential for use in bricks, tiles and glass ceramics. AB - The characteristics of sewage sludge ash (SSA) and its use in ceramic applications pertaining to bricks, tiles and glass ceramics have been assessed using the globally published literature in the English medium. It is shown that SSA possesses similar chemical characteristics to established ceramic materials and under heat treatment achieves the targeted densification, strength increases and absorption reductions. In brick and tile applications, technical requirements relating to strength, absorption and durability are achievable, with merely manageable performance reductions with SSA as a partial clay replacement. Fluxing properties of SSA facilitate lower firing temperatures during ceramics production, although reductions in mix plasticity leads to higher forming water requirements. SSA glass ceramics attained strengths in excess of natural materials such as granite and marble and displayed strong durability properties. The thermal treatment and nature of ceramic products also effectively restricted heavy metal leaching to low levels. Case studies, predominantly in bricks applications, reinforce confidence in the material with suitable technical performances achieved in practical conditions. PMID- 27386980 TI - Model of an aquaponic system for minimised water, energy and nitrogen requirements. AB - Water and nutrient savings can be established by coupling water streams between interacting processes. Wastewater from production processes contains nutrients like nitrogen (N), which can and should be recycled in order to meet future regulatory discharge demands. Optimisation of interacting water systems is a complex task. An effective way of understanding, analysing and optimising such systems is by applying mathematical models. The present modelling work aims at supporting the design of a nearly emission-free aquaculture and hydroponic system (aquaponics), thus contributing to sustainable production and to food security for the 21st century. Based on the model, a system that couples 40 m(3) fish tanks and a hydroponic system of 1,000 m(2) can produce 5 tons of tilapia and 75 tons of tomato yearly. The system requires energy to condense and recover evaporated water, for lighting and heating, adding up to 1.3 GJ/m(2) every year. In the suggested configuration, the fish can provide about 26% of the N required in a plant cycle. A coupling strategy that sends water from the fish to the plants in amounts proportional to the fish feed input, reduces the standard deviation of the NO3(-) level in the fish cycle by 35%. PMID- 27386981 TI - Optimizing Cu(II) removal from aqueous solution by magnetic nanoparticles immobilized on activated carbon using Taguchi method. AB - This study synthesized magnetic nanoparticles (Fe(3)O(4)) immobilized on activated carbon (AC) and used them as an effective adsorbent for Cu(II) removal from aqueous solution. The effect of three parameters, including the concentration of Cu(II), dosage of Fe(3)O(4)/AC magnetic nanocomposite and pH on the removal of Cu(II) using Fe(3)O(4)/AC nanocomposite were studied. In order to examine and describe the optimum condition for each of the mentioned parameters, Taguchi's optimization method was used in a batch system and L9 orthogonal array was used for the experimental design. The removal percentage (R%) of Cu(II) and uptake capacity (q) were transformed into an accurate signal-to-noise ratio (S/N) for a 'larger-the-better' response. Taguchi results, which were analyzed based on choosing the best run by examining the S/N, were statistically tested using analysis of variance; the tests showed that all the parameters' main effects were significant within a 95% confidence level. The best conditions for removal of Cu(II) were determined at pH of 7, nanocomposite dosage of 0.1 gL(-1) and initial Cu(II) concentration of 20 mg L(-1) at constant temperature of 25 degrees C. Generally, the results showed that the simple Taguchi's method is suitable to optimize the Cu(II) removal experiments. PMID- 27386982 TI - Mainstream partial nitritation and anammox in a 200,000 m3/day activated sludge process in Singapore: scale-down by using laboratory fed-batch reactor. AB - A laboratory fed-batch reactor has been used to study under controlled conditions the performance of partial nitritation/anammox for the 200,000 m(3)/day step-feed activated sludge process at the Changi Water Reclamation Plant, Singapore. The similarity of the concentrations of NH(4), NO(2), NO(3), PO(4), suspended chemical oxygen demand (sCOD), pH, and alkalinity (ALK) between the on-site process and laboratory reactor illustrates that the laboratory fed-batch reactor can be used to simulate the site performance. The performance of the reactor fed by primary effluent illustrated the existence of anammox and heterotrophic denitrification and apparent excessive biological phosphorus removal as observed from the site. The performance of the reactor fed by final effluent proved the presence of anammox process on site. Both the laboratory reactor and on-site process showed that higher influent 5-day biochemical oxygen demand/total nitrogen (BOD(5)/TN) (COD/TN) ratio increases the nitrogen removal efficiency of the process. PMID- 27386983 TI - Flocculation kinetics mechanism and floc formation prepared by poly aluminum chloride coupled with polyacrylamide for ship ballast water. AB - The performance of flocculants prepared by poly aluminum chloride (PAC) and polyacrylamide (PAM) on treating ballast water collected at the Dalian new port area, the evaluation depending on the values of reaction parameters, and kinetics mechanism of flocculation were investigated in this study. Accordingly, the flocculants of 0.1 g.L(-1), prepared by mixing PAC of 10% with PAM of 2.00/00, enabled the removal rate of zooplankton and phytoplankton to reach 91% in ballast water at 20 degrees C. Based on flocculation kinetics mechanism analysis, the efficient vortex size during stirring should be larger than the floc particles, and gradient of fluctuating velocity provide the impetus for turbulence flocculation. The results of this study could be relevant to understanding particle-floc interactions during developmental flocculation, and during application of ballast water treatment. PMID- 27386984 TI - Development of slow sponge sand filter (SpSF) as a post-treatment of UASB-DHS reactor effluent treating municipal wastewater. AB - In this study, conventional slow sand filter (SSF) and modified slow sponge sand filter (SpSF) were investigated for the post-treatment of up-flow anaerobic sludge blanket (UASB)-down-flow hanging sponge (DHS) reactor effluent. The seasonal variation did not show significant differences in removal efficiencies of both filters. However in summer, both filters were able to achieve high total suspended solids and total biochemical oxygen demand removal averaging 97% and 99%, respectively. Contrary to organic removal, total nitrogen removal efficiency was satisfactory, showing increased removal efficiencies averaging 58% and 62% for SSF and SpSF in summer. On the other hand, average total coliform removal of SSF and SpSF was 4.2 logs and 4.4 logs and corresponding Escherichia coli removal was 4.0 logs and 4.1 logs, respectively. From our observation, it could be concluded that the relative performance of SpSF for nutrients and coliforms was better than SSF due to the effectiveness of sponge media over fine sands. Moreover, microbial community analysis revealed that the members of phylum Proteobacteria were predominant in the biofilms of both filters, which could have contributed to pollutant removal. Therefore, SpSF could be concluded to be a suitable post-treatment of UASB-DHS system in warmer conditions. PMID- 27386985 TI - Innovative method for recovery and valorization of hydroxytyrosol from olive mill wastewaters. AB - The nutritional properties of olive oil can be attributed to its oleic acid and phenolic compounds content, acting as natural oxidants to prevent human diseases. In particular, hydroxytyrosol has an anti-inflammatory action similar to omega 3 fatty acids from fish oil. The olive oil production was conducted by two extraction procedures: first, a two-phase extraction giving extra-virgin olive oil and humid pomace, second, a three-phase working process of humid pomace, obtaining another minimum quantity of extra-virgin olive oil, 'dry' pomace devoid of polyphenols, and mill wastewaters rich in anti-oxidant compounds. The aim of this processing was to employ water to extract the highest concentration of polyphenols from humid pomace and convey them in oil mill wastewaters for extraction. Processed olives were 37,200 kg, pomace deprived of polyphenols was equal to 20,400 kg and processing was performed with 500 kg of olives per hour. This method offers advantages of using cheap equipment and technical simplicity. PMID- 27386986 TI - Optimization of permeate flux produced by solar energy driven membrane distillation process using central composite design approach. AB - Membrane distillation (MD) is considered as a relatively high-energy requirement. To overcome this drawback, it is recommended to couple the MD process with solar energy as the renewable energy source in order to provide heat energy required to optimize its performance to produce permeate flux. In the present work, an original solar energy driven direct contact membrane distillation (DCMD) pilot plant was built and tested under actual weather conditions at Jeddah, KSA, in order to model and optimize permeate flux. The dependency of permeate flux on various operating parameters such as feed temperature (46.6-63.4 degrees C), permeate temperature (6.6-23.4 degrees C), feed flow rate (199-451L/h) and permeate flow rate (199-451L/h) was studied by response surface methodology based on central composite design approach. The analysis of variance (ANOVA) confirmed that all independent variables had significant influence on the model (where P value <0.05). The high coefficient of determination (R(2) = 0.9644 and R(adj)(2) = 0.9261) obtained by ANOVA demonstrated good correlation between experimental and predicted values of the response. The optimized conditions, determined using desirability function, were T(f) = 63.4 degrees C, Tp = 6.6 degrees C, Q(f) = 451L/h and Q(p) = 451L/h. Under these conditions, the maximum permeate flux of 6.122 kg/m(2).h was achieved, which was close to the predicted value of 6.398 kg/m(2).h. PMID- 27386987 TI - Role of low molecular weight organic acids on pyrite dissolution in aqueous systems: implications for catalytic chromium (VI) treatment. AB - A systematic study combining batch experiments with spectroscopic analyses was carried out to better understand the effects of various organic acids on pyrite dissolution and subsequent Cr(VI) removal in aqueous systems. Our results suggest that organic acids had no effect on total Fe dissolution from pyrite relative to systems containing no acid. However, while nearly 100% of total Fe dissolved from pyrite was in Fe(II) form in the absence of ligands, the addition of organic acids led to significant oxidation of Fe(II) species to Fe(III). The degree and extent of Fe(II) oxidation increased in the order: tartrate < salicylate < oxalate ~ citrate < EDTA. Except for salicylate (an aromatic compound), this stimulatory effect observed in Fe(II) oxidation was well correlated with the strength of Fe-ligand complexes. In systems containing Cr(VI), the amount of Fe dissolved increased significantly relative to non-Cr(VI) containing system, and the ligands enhanced the dissolution of surface oxidation products from pyrite. Overall, it is clear that the dissolution of pyrite with organic acids had very little effect on solution phase Cr(VI) removal, but significantly stimulated surface phase Cr(VI) reduction by removing surface oxidation products, and thus creating new surface sites for extended Cr(VI) removal. PMID- 27386988 TI - Methods for increasing the rate of anammox attachment in a sidestream deammonification MBBR. AB - Deammonification (partial nitritation-anammox) is a proven process for the treatment of high-nitrogen waste streams, but long startup time is a known drawback of this technology. In a deammonification moving bed biofilm reactor (MBBR), startup time could potentially be decreased by increasing the attachment rate of anammox bacteria (AMX) on virgin plastic media. Previous studies have shown that bacterial adhesion rates can be increased by surface modification or by the development of a preliminary biofilm. This is the first study on increasing AMX attachment rates in a deammonification MBBR using these methods. Experimental media consisted of three different wet-chemical surface treatments, and also media transferred from a full-scale mainstream fully nitrifying integrated fixed-film activated sludge (IFAS) reactor. Following startup of a full-scale deammonification reactor, the experimental media were placed in the full-scale reactor and removed for activity rate measurements and biomass testing after 1 and 2 months. The media transferred from the IFAS process exhibited a rapid increase in AMX activity rates (1.1 g/m(2)/day NH(4)(+) removal and 1.4 g/m(2)/day NO(2)(-) removal) as compared to the control (0.2 g/m(2)/day NH(4)(+) removal and 0.1 g/m(2)/day NO(2)(-) removal) after 1 month. Two out of three of the surface modifications resulted in significantly higher AMX activity than the control at 1 and 2 months. No nitrite oxidizing bacteria activity was detected in either the surface modified media or IFAS media batch tests. The results indicate that startup time of a deammonification MBBR could potentially be decreased through surface modification of the plastic media or through the transfer of media from a mature IFAS process. PMID- 27386989 TI - Simulation of infiltration facilities using the SEEP/W model and quantification of flood runoff reduction effect by the decrease in CN. AB - In this study, four infiltration facilities (permeable pavement, infiltration gutter, infiltration trench, and infiltration well) have been investigated and compared with their flood runoff reduction effect. The SEEP/W model was used to estimate the infiltration amount of each facility, and the flood runoff reduction effect was quantified by the decrease in curve number (CN). As a result of this study, we found that: (1) the infiltration could be successfully simulated by the SEEP/W model, whose result could also be quantified effectively by the decrease in CN; (2) among the four infiltration facilities considered in this study, the infiltration well and infiltration trench were found to be most efficient and economical; (3) finally, the intervention effect of the nearby infiltration facility was found not so significant. In an extreme case where the infiltration wells were located at 1 m interval, the intervention effect was found to be just 1%. PMID- 27386990 TI - Effects of FeCl3 addition on the operation of a staged anaerobic fluidized membrane bioreactor (SAF-MBR). AB - The effects on sulfur removal and membrane fouling resulting from FeCl(3) addition to an anaerobic fluidized membrane bioreactor (AFMBR) in a staged AFMBR (SAF-MBR) was investigated. Total sulfur removal in the SAF-MBR was 42-59% without FeCl(3) addition, but increased to 87-95% with FeCl(3) addition. Sulfide removal in the AFMBR increased to 90% with addition of FeCl(3) at a molar Fe(3+)/S ratio of 0.54 and to 95% when the ratio was increased to 0.95. Effluent sulfide concentration then decreased to 0.3-0.6 mg/L. Phosphate removals were only 19 and 37% with the above added FeCl(3) ratios, indicating that iron removed sulfide more readily than phosphate. Neither chemical oxygen demand nor biochemical oxygen demand removal efficiencies were affected by the addition of FeCl(3). When the AFMBR permeate became exposed to air, light brown particles were formed from effluent Fe(2+) oxidation to Fe(3+). FeCl(3) addition, while beneficial for sulfide removal, did increase the membrane fouling rate due to the deposition of inorganic precipitates in the membrane pores. PMID- 27386991 TI - Performance of a fixed-bed biofilm reactor with microbubble aeration in aerobic wastewater treatment. AB - Microbubble aeration is supposed to be highly efficient for oxygen supply in aerobic wastewater treatment. In the present study, the performance of a fixed bed biofilm reactor microbubble-aerated using a Shirasu porous glass (SPG) membrane system was investigated when treating synthetic municipal wastewater. The biofilm formation on the carriers was enhanced with microbubble aeration due to the strong adhesion of microbubbles to the solid surface. The dissolved oxygen concentration, the removals of chemical oxygen demand (COD) and nitrogen, and the oxygen utilization efficiency were influenced by the organic loading rate at a certain oxygen supply capacity. The relatively optimal organic loading rate was determined as 0.82 kgCOD/(m(3)d) when the oxygen supply capacity was 0.93 kgO(2)/(m(3)d), where COD and ammonia removal efficiencies were 91.7% and 53.9%, respectively. The corresponding SPG membrane area-based COD removal capacity was 6.88 kgCOD/(m(2)d). The oxygen utilization efficiency of microbubble aeration was obviously higher compared to conventional bubble aeration. The simultaneous nitrification and denitrification occurred in the biofilm reactor and the total nitrogen removal efficiency of 50.4% was achieved under these conditions. In addition, the increase in air supply capacity of the SPG membrane system was suggested to improve its energy utilization efficiency. PMID- 27386992 TI - A venturi device reduces membrane fouling in a submerged membrane bioreactor. AB - In this study, for the first time, a venturi device was integrated into a submerged membrane bioreactor (MBR) to improve membrane surface cleaning and bioreactor oxygenation. The performances of a blower and the venturi device were compared in terms of membrane fouling and bioreactor oxygenation. Upon comparing membrane fouling, the performances were similar for a low operation flux (18 L/m(2).h); however, at a medium flux (32 L/m(2).h), the venturi system operated 3.4 times longer than the blower system, and the final transmembrane pressure was one-third that of the blower system. At the highest flux studied (50 L/m(2).h), the venturi system operated 5.4 times longer than the blower system. The most notable advantage of using a venturi device was that the dissolved oxygen (DO) concentration of the MBR was in the range of 7 to 8 mg/L at a 3 L/min aeration rate, while the DO concentration of the MBR was inadequate (a maximum of 0.29 mg/L) in the blower system. A clean water oxygenation test at a 3 L/min aeration rate indicated that the standard oxygen transfer rate for the venturi system was 9.5 times higher than that of the blower system. PMID- 27386994 TI - Application of Fe-Cu binary oxide nanoparticles for the removal of hexavalent chromium from aqueous solution. AB - The adsorption process has been used as an effective technique for the removal of metal ions from aqueous solutions. Groundwater remediation by nanoparticles has received interest in recent years. In the present study, a binary metal oxide of Fe-Cu was prepared and used for the removal of hexavalent chromium from aqueous solution. Batch experiments were performed to investigate the effects of initial Cr (VI) concentration, dose of adsorbent, and pH of solution on the removal efficiency of Cr (VI). The prepared nanostructured Fe-Cu binary oxides were able to reduce the concentration of Cr (VI) in aqueous solution. Binary metal oxides nanoparticle exhibited an outstanding ability to remove Cr (VI) due to high surface area, low particle size, and high inherent activity. The percentage removal efficiency of Cr (VI) increased with nanoparticles doses (0.1 g L(-1)-2.5 g L(-1)), whereas it decreased with initial Cr (VI) concentration (1 mg L(-1)-25 mg L(-1)) and with pH (3-9). The Freundlich model was found to be the better fit for adsorption isotherm. The prepared nanomaterial was characterized using powder X-ray diffraction, scanning electron microscopy (SEM), and ultraviolet (UV) visible spectroscopy. It showed that the Fe-Cu binary oxides were formed in single phase. SEM micrograph showed aggregates with many nano-sized particles. UV visible spectroscopy showed quantum confinement effect. PMID- 27386993 TI - Migration and transformation characteristics of DOM in fine sand and marl rock. AB - This paper mainly studied migration and transformation characteristics of dissolved organic matter (DOM) in underground aquifers. To achieve the research purpose, we carried out the dynamic column experiments of the DOM at different conditions indoors. In the experiment, the water of Wujiang River from Pingdingshan Coal-field is used as water sample, meanwhile, fine sand and marl rock are used as testing rock sample. A comparative study on migration and transformation characteristics of the DOM in different rock samples is done. The results show that, in the fine sand, the main effects are convection and dispersion, while the adsorption and biological effects are very weak. However, in the marl rock, besides existing convection and dispersion, the adsorption and biological effect are quite significant. And in the marl rock, convection and dispersion plays a major role in the early experiment, while adsorption is the main effect in the medium term, then the biodegradation dominates the final stage. With the increasing of temperature and seepage velocity in the fine sand, the impact of the convection effect becomes gradually weak, the dispersion effect gradually enhances, and, however, convection effect is still playing a dominant role. With the temperature rising in the marl rock, the adsorption effect becomes weak, but biodegradation is enhanced. As the seepage velocity increases in the marl rock, the adsorption and biodegradation both decrease. PMID- 27386995 TI - An expert system with radial basis function neural network based on decision trees for predicting sediment transport in sewers. AB - In this study, an expert system with a radial basis function neural network (RBF NN) based on decision trees (DT) is designed to predict sediment transport in sewer pipes at the limit of deposition. First, sensitivity analysis is carried out to investigate the effect of each parameter on predicting the densimetric Froude number (Fr). The results indicate that utilizing the ratio of the median particle diameter to pipe diameter (d/D), ratio of median particle diameter to hydraulic radius (d/R) and volumetric sediment concentration (C(V)) as the input combination leads to the best Fr prediction. Subsequently, the new hybrid DT-RBF method is presented. The results of DT-RBF are compared with RBF and RBF-particle swarm optimization (PSO), which uses PSO for RBF training. It appears that DT-RBF is more accurate (R(2) = 0.934, MARE = 0.103, RMSE = 0.527, SI = 0.13, BIAS = 0.071) than the two other RBF methods. Moreover, the proposed DT-RBF model offers explicit expressions for use by practicing engineers. PMID- 27386996 TI - Application of central composite design and artificial neural network in modeling of reactive blue 21 dye removal by photo-ozonation process. AB - The present study deals with use of central composite design (CCD) and artificial neural network (ANN) in modeling and optimization of reactive blue 21 (RB21) removal from aqueous media under photo-ozonation process. Four effective operational parameters (including: initial concentration of RB21, O(3) concentration, UV light intensity and reaction time) were chosen and the experiments were designed by CCD based on response surface methodology (RSM). The obtained results from the CCD model were used in modeling the process by ANN. Under optimum condition (O(3) concentration of 3.95 mg L(-1), UV intensity of 20.5 W m(-2), reaction time of 7.77 min and initial dye concentration of 40.21 mg L(-1)), RB21 removal efficiency reached to up 98.88%. A topology of ANN with a three-layer consisting of four input neurons, 14 hidden neurons and one output neuron was designed. The relative significance of each major factor was calculated based on the connection weights of the ANN model. Dye and ozone concentrations were the most important variables in the photo-ozonation of RB21, followed by reaction time and UV light intensity. The comparison of predicted values by CCD and ANN with experimental results showed that both methods were highly efficient in the modeling of the process. PMID- 27386997 TI - Pollutant characteristics of road deposited sediments collected by road sweeping. AB - Road deposited sediments (RDS) swept from highways in South Korea were characterized to quantitatively evaluate the reduction in non-point source pollutants by sweeping. The swept RDS consisted primarily of sand (63 MUm to 2 mm) particles (80.34 +/- 8.33% of total weight) highly contaminated by organics, nutrients and heavy metals. The average concentrations of total organic carbon (TOC), biochemical oxygen demand (BOD), volatile solids (VS), total nitrogen (T N), and total phosphorus (T-P) were 20.17 +/- 9.13, 1.04 +/- 0.62, 39.92 +/- 16.55, 1.99 +/- 0.96, and 0.54 +/- 0.19 g kg(-1) (+/-one standard deviation), respectively, for 63 MUm to 2 mm RDS. The concentrations of the pollutants were high for RDS smaller than 63 MUm, but most of the mass was associated with the 63 MUm to 2 mm RDS. The results suggest that the pollutants associated with RDS swept from highways originated mainly from engine wear, exhaust emissions, and tire wear. These results were different from the RDS on roads in residential and commercial areas, where natural particles and brake wear contribute significantly to RDS. In addition, the reductions in TOC, BOD, VS, T-N, T-P, Cu, Pb, Zn, Fe, and As based on the swept RDS measurements were calculated to be 3,355.3, 175.1, 6,621.4, 323.0, 88.3, 30.3, 13.7, 1.0, 303.4, 11,198.7, and 0.4 g km(-1), respectively.